PMID- 23112709
TI  - Voltamperometric discrimination of urea and melamine adulterated skimmed milk
      powder.
AB  - Nitrogen compounds like urea and melamine are known to be commonly used for milk
      adulteration resulting in undesired intoxication; a well-known example is the
      Chinese episode occurred in 2008. The development of a rapid, reliable and
      economic test is of relevance in order to improve adulterated milk
      identification. Cyclic voltammetry studies using an Au working electrode were
      performed on adulterated and non-adulterated milk samples from different
      independent manufacturers. Voltammetric data and their first derivative were
      subjected to functional principal component analysis (f-PCA) and correctly
      classified by the KNN classifier. The adulterated and non-adulterated milk
      samples showed significant differences. Best results of prediction were obtained
      with first derivative data. Detection limits in milk samples adulterated with 1%
      of its total nitrogen derived from melamine or urea were as low as 85.0 mg . L(
      1) and 121.4 mg . L(-1), respectively. We present this method as a fast and
      robust screening method for milk adulteration analysis and prevention of food
      intoxication.

PMID- 23112713
TI  - Fall detection with the support vector machine during scripted and continuous
      unscripted activities.
AB  - In recent years, the number of proposed fall-detection systems that have been
      developed has increased dramatically. A threshold-based algorithm utilizing an
      accelerometer has been used to detect low-complexity falling activities. In this
      study, we defined activities in which the body's center of gravity quickly
      declines as falling activities of daily life (ADLs). In the non-falling ADLs, we
      also focused on the body's center of gravity. A hyperplane of the support vector
      machine (SVM) was used as the separating plane to replace the traditional
      threshold method for the detection of falling ADLs. The scripted and continuous
      unscripted activities were performed by two groups of young volunteers (20
      subjects) and one group of elderly volunteers (five subjects). The results showed
      that the four parameters of the input vector had the best accuracy with 99.1% and
      98.4% in the training and testing, respectively. For the continuous unscripted
      test of one hour, there were two and one false positive events among young
      volunteers and elderly volunteers, respectively.

PMID- 23112714
TI  - Surface modification on acoustic wave biosensors for enhanced specificity.
AB  - Changes in mass loading on the surface of acoustic biosensors result in output
      frequency shifts which provide precise measurements of analytes. Therefore, to
      detect a particular biomarker, the sensor delay path must be judiciously designed
      to maximize sensitivity and specificity. B-cell lymphoma 2 protein (Bcl-2) found
      in urine is under investigation as a biomarker for non-invasive early detection
      of ovarian cancer. In this study, surface chemistry and biofunctionalization
      approaches were evaluated for their effectiveness in presenting antibodies for
      Bcl-2 capture while minimizing non-specific protein adsorption. The optimal
      combination of sequentially adsorbing protein A/G, anti-Bcl-2 IgG and Pluronic
      F127 onto a hydrophobic surface provided the greatest signal-to-noise ratio and
      enabled the reliable detection of Bcl-2 concentrations below that previously
      identified for early stage ovarian cancer as characterized by a modified ELISA
      method. Finally, the optimal surface modification was applied to a prototype
      acoustic device and the frequency shift for a range of Bcl-2 concentration was
      quantified to demonstrate the effectiveness in surface acoustic wave (SAW)-based
      detection applications. The surface functionalization approaches demonstrated
      here to specifically and sensitively detect Bcl-2 in a working ultrasonic MEMS
      biosensor prototype can easily be modified to detect additional biomarkers and
      enhance other acoustic biosensors.

PMID- 23112716
TI  - Multiple applications of Alamar Blue as an indicator of metabolic function and
      cellular health in cell viability bioassays.
AB  - Accurate prediction of the adverse effects of test compounds on living systems,
      detection of toxic thresholds, and expansion of experimental data sets to include
      multiple toxicity end-point analysis are required for any robust screening
      regime. Alamar Blue is an important redox indicator that is used to evaluate
      metabolic function and cellular health. The Alamar Blue bioassay has been
      utilized over the past 50 years to assess cell viability and cytotoxicity in a
      range of biological and environmental systems and in a number of cell types
      including bacteria, yeast, fungi, protozoa and cultured mammalian and piscine
      cells. It offers several advantages over other metabolic indicators and other
      cytotoxicity assays. However, as with any bioassay, suitability must be
      determined for each application and cell model. This review seeks to highlight
      many of the important considerations involved in assay use and design in addition
      to the potential pitfalls.

PMID- 23112726
TI  - Unobstructive Body Area Networks (BAN) for efficient movement monitoring.
AB  - The technological advances in medical sensors, low-power microelectronics and
      miniaturization, wireless communications and networks have enabled the appearance
      of a new generation of wireless sensor networks: the so-called wireless body area
      networks (WBAN). These networks can be used for continuous monitoring of vital
      parameters, movement, and the surrounding environment. The data gathered by these
      networks contributes to improve users' quality of life and allows the creation of
      a knowledge database by using learning techniques, useful to infer abnormal
      behaviour. In this paper we present a wireless body area network architecture to
      recognize human movement, identify human postures and detect harmful activities
      in order to prevent risk situations. The WBAN was created using tiny, cheap and
      low-power nodes with inertial and physiological sensors, strategically placed on
      the human body. Doing so, in an as ubiquitous as possible way, ensures that its
      impact on the users' daily actions is minimum. The information collected by these
      sensors is transmitted to a central server capable of analysing and processing
      their data. The proposed system creates movement profiles based on the data sent
      by the WBAN's nodes, and is able to detect in real time any abnormal movement and
      allows for a monitored rehabilitation of the user.

PMID- 23112727
TI  - Classification of fruits using computer vision and a multiclass support vector
      machine.
AB  - Automatic classification of fruits via computer vision is still a complicated
      task due to the various properties of numerous types of fruits. We propose a
      novel classification method based on a multi-class kernel support vector machine
      (kSVM) with the desirable goal of accurate and fast classification of fruits.
      First, fruit images were acquired by a digital camera, and then the background of
      each image was removed by a split-and-merge algorithm; Second, the color
      histogram, texture and shape features of each fruit image were extracted to
      compose a feature space; Third, principal component analysis (PCA) was used to
      reduce the dimensions of feature space; Finally, three kinds of multi-class SVMs
      were constructed, i.e., Winner-Takes-All SVM, Max-Wins-Voting SVM, and Directed
      Acyclic Graph SVM. Meanwhile, three kinds of kernels were chosen, i.e., linear
      kernel, Homogeneous Polynomial kernel, and Gaussian Radial Basis kernel; finally,
      the SVMs were trained using 5-fold stratified cross validation with the reduced
      feature vectors as input. The experimental results demonstrated that the Max-Wins
      Voting SVM with Gaussian Radial Basis kernel achieves the best classification
      accuracy of 88.2%. For computation time, the Directed Acyclic Graph SVMs performs
      swiftest.

PMID- 23112731
TI  - Species discrimination among three kinds of puffer fish using an electronic nose
      combined with olfactory sensory evaluation.
AB  - Species discrimination among three kinds of puffer fish, Takifugu obscurus,
      Takifugu flavidus and Takifugu rubripes, was conducted using an electronic nose
      combined with olfactory sensory evaluation. All data were treated by multivariate
      data processing based on principal component analysis (PCA) and discriminant
      factor analysis (DFA). The results showed the discriminant model by PCA method
      and DFA method. Using PCA and DFA, it was shown that the electronic nose was able
      to reasonably distinguish between each of the eleven puffer fish groups, with a
      discrimination index of 85. The olfactory sensory evaluation was undertaken in
      accordance to Sensory analysis-Methodology-Initiation and training of assessors
      in the detection and recognition of odors (BS ISO 5496-2006), and the results
      showed that the evaluation was able to identify puffer fish samples according to
      their species, geographical origin and age. Results from this analysis
      demonstrate that the E-nose can be used to complement the discrimination of odors
      by sensory evaluation from the three species of puffer fish studied here.

PMID- 23112728
TI  - A SPR aptasensor for detection of avian influenza virus H5N1.
AB  - Rapid and specific detection of avian influenza virus (AIV) is urgently needed
      due to the concerns over the potential outbreaks of highly pathogenic H5N1
      influenza in animals and humans. Aptamers are artificial oligonucleic acids that
      can bind specific target molecules, and show comparable affinity for target
      viruses and better thermal stability than monoclonal antibodies. The objective of
      this research was to use a DNA-aptamer as the specific recognition element in a
      portable Surface Plasmon Resonance (SPR) biosensor for rapid detection of AIV
      H5N1 in poultry swab samples. A SPR biosensor was fabricated using selected
      aptamers that were biotinylated and then immobilized on the sensor gold surface
      coated with streptavidin via streptavidin-biotin binding. The immobilized
      aptamers captured AIV H5N1 in a sample solution, which caused an increase in the
      refraction index (RI). After optimizing the streptavidin and aptamer parameters,
      the results showed that the RI value was linearly related (R(2) = 0.99) to the
      concentration of AIV in the range of 0.128 to 1.28 HAU. Negligible signal (<4% of
      H5N1) was observed from six non-target AIV subtypes. The AIV H5N1 in poultry swab
      samples with concentrations of 0.128 to 12.8 HAU could be detected using this
      aptasensor in 1.5 h.

PMID- 23112734
TI  - Efficient security mechanisms for mHealth applications using wireless body sensor
      networks.
AB  - Recent technological advances in wireless communications and physiological
      sensing allow miniature, lightweight, ultra-low power, intelligent monitoring
      devices, which can be integrated into a Wireless Body Sensor Network (WBSN) for
      health monitoring. Physiological signals of humans such as heartbeats,
      temperature and pulse can be monitored from a distant location using tiny
      biomedical wireless sensors. Hence, it is highly essential to combine the
      ubiquitous computing with mobile health technology using wireless sensors and
      smart phones to monitor the well-being of chronic patients such as cardiac,
      Parkinson and epilepsy patients. Since physiological data of a patient are highly
      sensitive, maintaining its confidentiality is highly essential. Hence, security
      is a vital research issue in mobile health (mHealth) applications, especially if
      a patient has an embarrassing disease. In this paper a three tier security
      architecture for the mHealth application is proposed, in which light weight data
      confidentiality and authentication protocols are proposed to maintain the privacy
      of a patient. Moreover, considering the energy and hardware constraints of the
      wireless body sensors, low complexity data confidential and authentication
      schemes are designed. Performance evaluation of the proposed architecture shows
      that they can satisfy the energy and hardware limitations of the sensors and
      still can maintain the secure fabrics of the wireless body sensor networks.
      Besides, the proposed schemes can outperform in terms of energy consumption,
      memory usage and computation time over standard key establishment security
      scheme.

PMID- 23112739
TI  - Validation processes of protein biomarkers in serum--a cross platform comparison.
AB  - Due to insufficient biomarker validation and poor performances in diagnostic
      assays, the candidate biomarker verification process has to be improved. Multi
      analyte immunoassays are the tool of choice for the identification and detailed
      validation of protein biomarkers in serum. The process of identification and
      validation of serum biomarkers, as well as their implementation in diagnostic
      routine requires an application of independent immunoassay platforms with the
      possibility of high-throughput. This review will focus on three main multi
      analyte immunoassay platforms: planar microarrays, multiplex bead systems and,
      array-based surface plasmon resonance (SPR) chips. Recent developments of each
      platform will be discussed for application in clinical proteomics, principles,
      detection methods, and performance strength. The requirements for specific
      surface functionalization of assay platforms are continuously increasing. The
      reasons for this increase is the demand for highly sensitive assays, as well as
      the reduction of non-specific adsorption from complex samples, and with it high
      signal-to-noise-ratios. To achieve this, different support materials were adapted
      to the immobilized biomarker/ligand, allowing a high binding capacity and
      immobilization efficiency. In the case of immunoassays, the immobilized ligands
      are proteins, antibodies or peptides, which exhibit a diversity of chemical
      properties (acidic/alkaline; hydrophobic/hydrophilic; secondary or tertiary
      structure/linear). Consequently it is more challenging to develop immobilization
      strategies necessary to ensure a homogenous covered surface and reliable assay in
      comparison to DNA immobilization. New developments concerning material support
      for each platform are discussed especially with regard to increase the
      immobilization efficiency and reducing the non-specific adsorption from complex
      samples like serum and cell lysates.

PMID- 23112743
TI  - Tree height growth measurement with single-scan airborne, static terrestrial and
      mobile laser scanning.
AB  - This study explores the feasibility of applying single-scan airborne, static
      terrestrial and mobile laser scanning for improving the accuracy of tree height
      growth measurement. Specifically, compared to the traditional works on forest
      growth inventory with airborne laser scanning, two issues are regarded: "Can the
      new technique characterize the height growth for each individual tree?" and "Can
      this technique refine the minimum growth-discernable temporal interval further?"
      To solve these two puzzles, the sampling principles of the three laser scanning
      modes were first examined, and their error sources against the task of tree-top
      capturing were also analyzed. Next, the three-year growths of 58 Nordic maple
      trees (Crimson King) for test were intermittently surveyed with one type of laser
      scanning each time and then analyzed by statistics. The evaluations show that the
      height growth of each individual tree still cannot be reliably characterized even
      by single-scan terrestrial laser scanning, and statistical analysis is necessary
      in this scenario. After Gaussian regression, it is found that the minimum
      temporal interval with distinguishable tree height growths can be refined into
      one month based on terrestrial laser scanning, far better than the two years
      deduced in the previous works based on airborne laser scanning. The associated
      mean growth was detected to be about 0.12 m. Moreover, the parameter of tree
      height generally under-estimated by airborne and even mobile laser scanning can
      be relatively revised by means of introducing static terrestrial laser scanning
      data. Overall, the effectiveness of the proposed technique is primarily
      validated.

PMID- 23112741
TI  - Effect-based tools for monitoring and predicting the ecotoxicological effects of
      chemicals in the aquatic environment.
AB  - Ecotoxicology faces the challenge of assessing and predicting the effects of an
      increasing number of chemical stressors on aquatic species and ecosystems. Herein
      we review currently applied tools in ecological risk assessment, combining
      information on exposure with expected biological effects or environmental water
      quality standards; currently applied effect-based tools are presented based on
      whether exposure occurs in a controlled laboratory environment or in the field.
      With increasing ecological relevance the reproducibility, specificity and thus
      suitability for standardisation of methods tends to diminish. We discuss the use
      of biomarkers in ecotoxicology including ecotoxicogenomics-based endpoints, which
      are becoming increasingly important for the detection of sublethal effects.
      Carefully selected sets of biomarkers allow an assessment of exposure to and
      effects of toxic chemicals, as well as the health status of organisms and, when
      combined with chemical analysis, identification of toxicant(s). The promising
      concept of "adverse outcome pathways (AOP)" links mechanistic responses on the
      cellular level with whole organism, population, community and potentially
      ecosystem effects and services. For most toxic mechanisms, however, practical
      application of AOPs will require more information and the identification of key
      links between responses, as well as key indicators, at different levels of
      biological organization, ecosystem functioning and ecosystem services.

PMID- 23112746
TI  - A real-time cardiac arrhythmia classification system with wearable sensor
      networks.
AB  - Long term continuous monitoring of electrocardiogram (ECG) in a free living
      environment provides valuable information for prevention on the heart attack and
      other high risk diseases. This paper presents the design of a real-time wearable
      ECG monitoring system with associated cardiac arrhythmia classification
      algorithms. One of the striking advantages is that ECG analog front-end and on
      node digital processing are designed to remove most of the noise and bias. In
      addition, the wearable sensor node is able to monitor the patient's ECG and
      motion signal in an unobstructive way. To realize the real-time medical analysis,
      the ECG is digitalized and transmitted to a smart phone via Bluetooth. On the
      smart phone, the ECG waveform is visualized and a novel layered hidden Markov
      model is seamlessly integrated to classify multiple cardiac arrhythmias in real
      time. Experimental results demonstrate that the clean and reliable ECG waveform
      can be captured in multiple stressed conditions and the real-time classification
      on cardiac arrhythmia is competent to other workbenches.

PMID- 23112747
TI  - Aging, Disablement, and Dying: Using Time-as-Process and Time-as-Resources
      Metrics to Chart Late-Life Change.
AB  - Time is a vehicle that can be used to represent aging-related processes and to
      index the amount of aging-related resources or burdens individuals have
      accumulated. Using data on cognitive (memory) performance from two Swedish
      studies of the elderly (OCTO and OCTO-TWIN), we illustrate how time-as-process
      and time-as-resources/burdens time metrics can be articulated and incorporated
      within a growth curve modeling framework. Our results highlight the possibilities
      for representing the contributions of primary, secondary, and tertiary aspects of
      aging to late-life changes in cognitive and other domains of functioning.

PMID- 23112748
TI  - The Amber ff99 Force Field Predicts Relative Free Energy Changes for RNA Helix
      Formation.
AB  - The ability of the Amber ff99 force field to predict relative free energies of
      RNA helix formation was investigated. The test systems were three hexaloop RNA
      hairpins with identical loops and varying stems. The potential of mean force of
      stretching the hairpins from the native state to an extended conformation was
      calculated with umbrella sampling. Because the hairpins have identical loop
      sequence, the differences in free energy changes are only from the stem
      composition. The Amber ff99 force field was able to correctly predict the order
      of stabilities of the hairpins, although the magnitude of the free energy change
      is larger than that determined by optical melting experiments. The two
      measurements cannot be compared directly because the unfolded state in the
      optical melting experiments is a random coil, while the end state in the umbrella
      sampling simulations was an elongated chain. The calculations can be compared to
      reference data by using a thermodynamic cycle. By applying the thermodynamic
      cycle to the transitions between the hairpins using simulations and nearest
      neighbor data, agreement was found to be within the sampling error of
      simulations, thus demonstrating that ff99 force field is able to accurately
      predict relative free energies of RNA helix formation.

PMID- 23112749
TI  - Beware of Hemizygous Deletions That May Unmask Deleterious Variants.

PMID- 23112750
TI  - Applying Genomic Analysis to Newborn Screening.
AB  - Large-scale genomic analysis such as whole-exome and whole-genome sequencing is
      becoming increasingly prevalent in the research arena. Clinically, many potential
      uses of this technology have been proposed. One such application is the extension
      or augmentation of newborn screening. In order to explore this application, we
      examined data from 3 children with normal newborn screens who underwent whole
      exome sequencing as part of research participation. We analyzed sequence
      information for 151 selected genes associated with conditions ascertained by
      newborn screening. We compared findings with publicly available databases and
      results from over 500 individuals who underwent whole-exome sequencing at the
      same facility. Novel variants were confirmed through bidirectional
      dideoxynucleotide sequencing. High-density microarrays (Illumina Omni1-Quad) were
      also performed to detect potential copy number variations affecting these genes.
      We detected an average of 87 genetic variants per individual. After excluding
      artifacts, 96% of the variants were found to be reported in public databases and
      have no evidence of pathogenicity. No variants were identified that would predict
      disease in the tested individuals, which is in accordance with their normal
      newborn screens. However, we identified 6 previously reported variants and 2
      novel variants that, according to published literature, could result in affected
      offspring if the reproductive partner were also a mutation carrier; other
      specific molecular findings highlight additional means by which genomic testing
      could augment newborn screening.

PMID- 23112751
TI  - Chromothripsis Challenges the Germline.

PMID- 23112752
TI  - Investigation of TBR1 Hemizygosity: Four Individuals with 2q24 Microdeletions.
AB  - TBR1 encodes a transcription factor with critical roles in corticogenesis,
      including cortical neuron migration and axon pathfinding, establishment of
      regional and laminar identity of cortical neurons, and control of glutamatergic
      neuronal cell fate. Based upon TBR1's role in cortical development, we sought to
      investigate TBR1 hemizygosity in individuals referred for genetic evaluation of
      intellectual disability and developmental delay. We describe 4 patients with
      microdeletions identified by molecular cytogenetic techniques, encompassing TBR1
      and spanning 2q24.1q31.1, ranging in size from 2.17 to 12.34 Mb. Only the patient
      with the largest deletion had a possible cortical malformation. Mild
      ventriculomegaly is the only common brain anomaly, present in all patients; a
      Chiari I malformation is seen in 2 patients, and mega cisterna magna is seen in a
      third. Our findings are consistent with Tbr1 mouse models showing that
      hemizygosity of the gene requires additional genetic factors for the
      manifestation of severe structural brain malformations. Other syndromic features
      are present in these patients, including autism spectrum disorders, ocular
      colobomas, and craniosynostosis, features that are likely affected by the
      deletion of genes other than TBR1.

PMID- 23112753
TI  - A Diagnostic Algorithm for Mitochondrial Disorders in Estonian Children.
AB  - Mitochondrial disorders are a heterogeneous group of disorders affecting energy
      production of the body. Different consensus diagnostic criteria for mitochondrial
      disorders in childhood are available - Wolfson, Nijmegen and modified Walker
      criteria. Due to the extreme complexity of mitochondrial disorders in children,
      we decided to develop a diagnostic algorithm, applicable in clinical practice in
      Estonia, in order to identify patients with mitochondrial disorders among
      pediatric neonatology and neurology patients. Additionally, it was aimed to
      evaluate the live-birth prevalence of mitochondrial disorders in childhood.
      During the study period (2003-2009), a total of 22 children were referred to a
      muscle biopsy in suspicion of mitochondrial disorder based on the preliminary
      biochemical, metabolic and instrumental investigations. Enzymatic and/or
      molecular analysis confirmed mitochondrial disease in 5 of them - an SCO2 gene
      (synthesis of cytochrome c oxidase, subunit 2) defect, 2 cases of pyruvate
      dehydrogenase complex deficiency and 2 cases of combined complex I and IV
      deficiency. The live-birth prevalence for mitochondrial defects observed in our
      cohort was 1/20,764 live births. Our epidemiological data correlate well with
      previously published epidemiology data on mitochondrial diseases in childhood
      from Sweden and Australia, but are lower than in Finland.

PMID- 23112754
TI  - Shared Copy Number Variation in Simultaneous Nephroblastoma and Neuroblastoma due
      to Fanconi Anemia.
AB  - Concurrent emergence of nephroblastoma (Wilms Tumor; WT) and neuroblastoma (NB)
      is rare and mostly observed in patients with severe subtypes of Fanconi anemia
      (FA) with or without VACTER-L association (VL). We investigated the hypothesis
      that early consequences of genomic instability result in shared regions with copy
      number variation in different precursor cells that originate distinct embryonal
      tumors. We observed a newborn girl with FA and VL (aplasia of the thumbs, cloacal
      atresia (urogenital sinus), tethered cord at L3/L4, muscular ventricular septum
      defect, and horseshoe-kidney with a single ureter) who simultaneously acquired an
      epithelial-type WT in the left portion of the kidney and a poorly differentiated
      adrenal NB in infancy. A novel homozygous germline frameshift mutation in PALB2
      (c.1676_c1677delAAinsG) leading to protein truncation (pGln526ArgfsX1) inherited
      from consanguineous parents formed the genetic basis of FA-N. Spontaneous and
      induced chromosomal instability was detected in the majority of cells analyzed
      from peripheral lymphocytes, bone marrow, and cultured fibroblasts. Bone marrow
      cells also showed complex chromosome rearrangements consistent with the
      myelodysplastic syndrome at 11 months of age. Array-comparative genomic
      hybridization analyses of both WT and NB showed shared gains or amplifications
      within the chromosomal regions 11p15.5 and 17q21.31-q25.3, including genes that
      are reportedly implicated in tumor development such as IGF2, H19, WT2, BIRC5, and
      HRAS.

PMID- 23112755
TI  - A de novo sSMC(22) Characterized by High-Resolution Arrays in a Girl with Cat-Eye
      Syndrome without Coloboma.
AB  - Cat-eye syndrome (CES) results from trisomy or tetrasomy of proximal 22q
      originated by a small supernumerary marker chromosome (sSMC). Two critical
      regions for the major clinical features of CES (CESCRs) have been suggested;
      however, CES clinical presentation often does not correlate with the sSMC genetic
      content. We report here a CES girl without coloboma and carrier of a de novo type
      I sSMC(22) as determined by G- and C-banding, NOR staining and microarrays. This
      sSMC included 6 distal genes outside the original CESCR and led to a tetrasomy
      for 22q11.1-22q11.21. The patient's final karyotype was 47,XX,+psu
      dic(22)(q11.21).arr 22q11.1q11.21(15,250,000-17,035,860)*4 dn. The amplified
      region outside of CESCR included some genes that may be related to neurologic,
      heart and renal abnormalities. Conversely, even though the amplification included
      the CECR2 gene, a major candidate for eye features, there was no coloboma in the
      patient. The genetic delineation of the present sSMC further strengthens that the
      CES clinical presentation does not fit completely with the duplicated genetic
      content and that CES is actually a genomic disorder. Furthermore, since we
      observed no mosaicism, we believe that other mechanisms might be behind the
      variability of CES phenotypes as well, mainly those related with functional
      interactions among amplified genes.

PMID- 23112756
TI  - MOTA Syndrome: Molecular Genetic Confirmation of the Diagnosis in a Newborn with
      Previously Unreported Clinical Features.
AB  - MOTA syndrome, the acronym for Manitoba-oculo-tricho-anal syndrome (OMIM 248450),
      is a distinct autosomal recessive multiple malformation syndrome caused by
      mutations in the FREM1 gene (OMIM 608944). Eight patients with MOTA syndrome and
      a pathogenic FREM1 mutation have previously been documented. We report on a new
      male patient, 3.5 months old, with MOTA syndrome, who presented with the
      following features: bilateral incomplete cryptophthalmos with a completely fused,
      ill-defined upper eyelid and a keratinized cornea, hypertelorism, a broad tip of
      the nose, a circle-shaped whirl of hair on the forehead, and a low anorectal
      malformation, which could be corrected on day 2 of life without a colostomy. In
      expansion to the previously reported phenotype of MOTA syndrome, the patient
      showed characteristic features reported in patients with Fraser syndrome,
      including dysplastic ears, cutaneous syndactyly 3/4 of the hands and syndactyly
      2/3 of the right foot. Molecular analysis of FREM1 identified compound
      heterozygosity for a new frameshift deletion in exon 24 (c.4629delC,
      p.F1544SfsX62) and a previously reported missense mutation in exon 21 (c.3971T>G,
      p.L1324R). This report further extends the phenotype of MOTA syndrome and
      underscores the overlapping clinical spectrum of FRAS-FREM complex diseases.

PMID- 23112757
TI  - High Intellectual Function in Individuals with Mutation-Positive Microform
      Holoprosencephaly.
AB  - Holoprosencephaly is the most common malformation of the forebrain and typically
      results in severe neurocognitive impairment with accompanying midline facial
      anomalies. Holoprosencephaly is heterogeneous and may be caused by chromosome
      aberrations or environmental factors, occur in the context of a syndrome or be
      due to heterozygous mutations in over 10 identified genes. The presence of these
      mutations may result in an extremely wide spectrum of severity, ranging from
      brain malformations incompatible with life to individuals with normal brain
      findings and subtle midline facial differences. Typically, clinicians regard
      intellectual disability as a sign that a parent or relative of a severely
      affected patient may be a mildly affected mutation 'carrier' with what is termed
      microform holoprosencephaly. Here we present 5 patients with clear phenotypic
      signs of microform holoprosencephaly, all of whom have evidence of above-average
      intellectual function. In 4 of these 5 individuals, the molecular cause of
      holoprosencephaly has been identified and includes mutations affecting SHH, SIX3,
      GLI2, and FGF8. This report expands the phenotypic spectrum of holoprosencephaly
      and is important in the counseling of patient and affected families.

PMID- 23112758
TI  - How costs influence decision values for mixed outcomes.
AB  - The things that we hold dearest often require a sacrifice, as epitomized in the
      maxim "no pain, no gain." But how is the subjective value of outcomes established
      when they consist of mixtures of costs and benefits? We describe theoretical
      models for the integration of costs and benefits into a single value, drawing on
      both the economic and the empirical literatures, with the goal of rendering them
      accessible to the neuroscience community. We propose two key assays that go
      beyond goodness of fit for deciding between the dominant additive model and four
      varieties of interactive models. First, how they model decisions between costs
      when reward is not on offer; and second, whether they predict changes in reward
      sensitivity when costs are added to outcomes, and in what direction. We provide a
      selective review of relevant neurobiological work from a computational
      perspective, focusing on those studies that illuminate the underlying valuation
      mechanisms. Cognitive neuroscience has great potential to decide which of the
      theoretical models is actually employed by our brains, but empirical work has yet
      to fully embrace this challenge. We hope that future research improves our
      understanding of how our brain decides whether mixed outcomes are worthwhile.

PMID- 23112759
TI  - Finding a Needle in a Haystack: Identification of EGFP Tagged Neurons during
      Calcium Imaging by Means of Two-Photon Spectral Separation.
AB  - The combination of two-photon in vivo imaging and genetic labeling of specific
      cell types in the mouse brain is a powerful method to refine our understanding of
      brain circuitry and to dissect the contribution of specific neural classes to
      cortical function. The synthetic calcium indicators are the best fluorescent
      reporters for cellular activity that are presently available but their spectral
      proprieties are often overlapped with those of the fluorescent proteins used for
      genetic labeling. Such is the case of Oregon Green BAPTA1 and EGFP, the most
      widely used fluorophores for targeted two-photon imaging. The emission spectra of
      these molecules are virtually identical, precluding their separation by narrow
      band filters at the detector side. However, even if their one photon excitation
      spectra are very similar, their two-photon excitation spectra differ
      significantly: here we show how it is possible to exploit this difference to
      separate the relative contributions of EGFP and Oregon Green to the total
      fluorescence signal. This approach addresses two different issues: the unbiased
      detection of cells expressing EGFP in a cortical volume injected with Oregon
      Green, and the computation of the Ca(2+) insensitive fluorescence background. The
      latter data is essential for the quantitative comparison of the relative changes
      in Ca(2+) concentration between different cells, containing variable
      concentrations of EGFP. This strategy can be easily extended to any couple of
      fluorophores provided that have a different two-photon excitation spectra.

PMID- 23112760
TI  - A first glance on the molecular mechanisms of pheromone-plant odor interactions
      in moth antennae.

PMID- 23112762
TI  - Functional and evolutionary aspects of chemoreceptors.
AB  - The perception and processing of chemical signals from the environment is
      essential for any living systems and is most probably the first sense developed
      in life. This perspective discusses the physical limits of chemoreception and
      gives an overview on the receptor types developed during evolution to detect
      chemical signals from the outside world of an organism. It discusses the
      interaction of chemoreceptors with downstream signaling elements, especially the
      interaction between electrical and chemical signaling. It is further considered
      how the primary chemosignal is appropriately amplified. Three examples of
      chemosensory systems illustrate different strategies of such amplification.

PMID- 23112763
TI  - Enhancement of prominent texture cues in fly optic flow processing.

PMID- 23112764
TI  - Facilitation of dragonfly target-detecting neurons by slow moving features on
      continuous paths.
AB  - Dragonflies detect and pursue targets such as other insects for feeding and
      conspecific interaction. They have a class of neurons highly specialized for this
      task in their lobula, the "small target motion detecting" (STMD) neurons. One
      such neuron, CSTMD1, reaches maximum response slowly over hundreds of
      milliseconds of target motion. Recording the intracellular response from CSTMD1
      and a second neuron in this system, BSTMD1, we determined that for the neurons to
      reach maximum response levels, target motion must produce sequential local
      activation of elementary motion detecting elements. This facilitation effect is
      most pronounced when targets move at velocities slower than what was previously
      thought to be optimal. It is completely disrupted if targets are instantaneously
      displaced a few degrees from their current location. Additionally, we utilize a
      simple computational model to discount the parsimonious hypothesis that CSTMD1's
      slow build-up to maximum response is due to it incorporating a sluggish neural
      delay filter. Whilst the observed facilitation may be too slow to play a role in
      prey pursuit flights, which are typically rapidly resolved, we hypothesize that
      it helps maintain elevated sensitivity during prolonged, aerobatically intricate
      conspecific pursuits. Since the effect seems to be localized, it most likely
      enhances the relative salience of the most recently "seen" locations during such
      pursuit flights.

PMID- 23112761
TI  - The calcium-activated slow AHP: cutting through the Gordian knot.
AB  - The phenomenon known as the slow afterhyperpolarization (sAHP) was originally
      described more than 30 years ago in pyramidal cells as a slow, Ca(2+)-dependent
      afterpotential controlling spike frequency adaptation. Subsequent work showed
      that similar sAHPs were widely expressed in the brain and were mediated by a
      Ca(2+)-activated potassium current that was voltage-independent, insensitive to
      most potassium channel blockers, and strongly modulated by neurotransmitters.
      However, the molecular basis for this current has remained poorly understood. The
      sAHP was initially imagined to reflect the activation of a potassium channel
      directly gated by Ca(2+) but recent studies have begun to question this idea. The
      sAHP is distinct from the Ca(2+)-dependent fast and medium AHPs in that it
      appears to sense cytoplasmic [Ca(2+)](i) and recent evidence implicates proteins
      of the neuronal calcium sensor (NCS) family as diffusible cytoplasmic Ca(2+)
      sensors for the sAHP. Translocation of Ca(2+)-bound sensor to the plasma membrane
      would then be an intermediate step between Ca(2+) and the sAHP channels. Parallel
      studies strongly suggest that the sAHP current is carried by different potassium
      channel types depending on the cell type. Finally, the sAHP current is dependent
      on membrane PtdIns(4,5)P(2) and Ca(2+) appears to gate this current by increasing
      PtdIns(4,5)P(2) levels. Because membrane PtdIns(4,5)P(2) is essential for the
      activity of many potassium channels, these finding have led us to hypothesize
      that the sAHP reflects a transient Ca(2+)-induced increase in the local
      availability of PtdIns(4,5)P(2) which then activates a variety of potassium
      channels. If this view is correct, the sAHP current would not represent a unitary
      ionic current but the embodiment of a generalized potassium channel gating
      mechanism. This model can potentially explain the cardinal features of the sAHP,
      including its cellular heterogeneity, slow kinetics, dependence on cytoplasmic
      [Ca(2+)], high temperature-dependence, and modulation.

PMID- 23112766
TI  - Chemosensory learning and memory.

PMID- 23112765
TI  - Age-related neuronal loss in the rat brain starts at the end of adolescence.
AB  - Aging-related changes in the brain have been mostly studied through the
      comparison of young adult and very old animals. However, aging must be considered
      a lifelong process of cumulative changes that ultimately become evident at old
      age. To determine when this process of decline begins, we studied how the
      cellular composition of the rat brain changes from infancy to adolescence, early
      adulthood, and old age. Using the isotropic fractionator to determine total
      numbers of neuronal and non-neuronal cells in different brain areas, we find that
      a major increase in number of neurons occurs during adolescence, between 1 and 2
      3 months of age, followed by a significant trend of widespread and progressive
      neuronal loss that begins as early as 3 months of age, when neuronal numbers are
      maximal in all structures, until decreases in numbers of neurons become evident
      at 12 or 22 months of age. Our findings indicate that age-related decline in the
      brain begins as soon as the end of adolescence, a novel finding has important
      clinical and social implications for public health and welfare.

PMID- 23112767
TI  - Not all stressors are equal: behavioral and endocrine evidence for development of
      contextual fear conditioning after a single session of footshocks but not of
      immobilization.
AB  - Exposure of animals to footshocks (FS) in absence of any specific cue results in
      the development of fear to the compartment where shocks were given (contextual
      fear conditioning), and this is usually evaluated by time spent freezing.
      However, the extent to which contextual fear conditioning always develops when
      animals are exposed to other stressors is not known. In the present work we
      firstly demonstrated, using freezing, that exposure of adult rats to a single
      session of FS resulted in short-term and long-term contextual fear conditioning
      (freezing) that was paralleled by increased hypothalamic-pituitary-adrenal (HPA)
      activation. In contrast, using a similar design, no HPA or behavioral evidence
      for such conditioning was found after exposure to immobilization on boards (IMO),
      despite this stressor being of similar severity as FS on the basis of standard
      physiological measures of stress, including HPA activation. In a final experiment
      we directly compared the exposure to the two stressors in the same type of
      context and tested for the development of conditioning to the context and to a
      specific cue for IMO (the board). We observed the expected high levels of
      freezing and the conditioned HPA activation after FS, but not after IMO,
      regardless of the presence of the board during testing. Therefore, it can be
      concluded that development of fear conditioning to context or particular cues, as
      evaluated by either behavioral or endocrine measures, appears to be dependent on
      the nature of the aversive stimuli, likely to be related to biologically
      preparedness to establish specific associations.

PMID- 23112768
TI  - Socio-cultural effects on children's initiation of joint attention.
AB  - Exchanging gazes with a social partner in response to an event in the environment
      is considered an effective means to direct attention, share affective
      experiences, and highlight a target in the environment. This behavior appears
      during infancy and plays an important role in children's learning and in shaping
      their socio-emotional development. It has been suggested that cultural values of
      the community affect socio-emotional development through attentional dynamics of
      social reference (Rogoff et al., 1993). Maturational processes of brain-circuits
      have been found to mediate socio-cultural learning and the behavioral
      manifestation of cultural norms starting at preschool age (Nelson and Guyer,
      2011). The aim of the current study was to investigate the relations between
      cultural ecology levels and children's joint attention (JA). Initiation of JA
      bids was studied empirically as a function of the level of social load of the
      target toy (3 levels), the community level of adherence to traditional values (3
      levels), parental education (2 levels), and gender. Sixty-two kindergarten aged
      children were enrolled in a structured toy-exploration task, during which they
      were presented with toys of various social loads, with social agents (i.e.,
      mother and experimenter) present nearby, and non-social distracters presented
      intermittently. Measurements included the child's number of JA bids and the
      extent of positive affect. Analysis of variance indicated that the child's
      initiation of JA toward the social partner was affected by all levels of cultural
      ecology (i.e., toy's social load, adherence to tradition values, parental
      education, gender), thus supporting the study's hypotheses. The effects were such
      that overall, children, particularly girls' JA initiation was augmented in social
      toys and moderated by the socio-cultural variables. These results suggest that
      cultural ecology is related to children's JA, thereby scaffolding initiation of
      social sharing cues between children and adults. JA plays a role in adjusting
      children's internal representations of their respective ecological environment.

PMID- 23112769
TI  - When does hearing laughter draw attention to happy faces? Task relevance
      determines the influence of a crossmodal affective context on emotional
      attention.
AB  - Prior evidence has shown that a person's affective context influences attention
      to emotional stimuli. The present study investigated whether a crossmodal
      affective context that is induced by remembering an emotional sound modulates
      attention to visual emotional stimuli. One group of participants had to remember
      a positive, negative, or neutral sound during each trial of a dot probe paradigm.
      A second group of participants also had to encode the valence of the sound. The
      results revealed that attention was preferentially deployed to stimuli that were
      emotionally congruent to the affective context. However, this effect was only
      evident when participants had to encode the valence of the affective context.
      These findings suggest that a crossmodal affective context modulates the
      deployment of attention to emotional stimuli provided that the affective
      connotation of the context is task-relevant.

PMID- 23112771
TI  - Does rhythmic entrainment represent a generalized mechanism for organizing
      computation in the brain?

PMID- 23112772
TI  - Evolving a neural olfactorimotor system in virtual and real olfactory
      environments.
AB  - To provide a platform to enable the study of simulated olfactory circuitry in
      context, we have integrated a simulated neural olfactorimotor system with a
      virtual world which simulates both computational fluid dynamics as well as a
      robotic agent capable of exploring the simulated plumes. A number of the elements
      which we developed for this purpose have not, to our knowledge, been previously
      assembled into an integrated system, including: control of a simulated agent by a
      neural olfactorimotor system; continuous interaction between the simulated robot
      and the virtual plume; the inclusion of multiple distinct odorant plumes and
      background odor; the systematic use of artificial evolution driven by
      olfactorimotor performance (e.g., time to locate a plume source) to specify
      parameter values; the incorporation of the realities of an imperfect physical
      robot using a hybrid model where a physical robot encounters a simulated plume.
      We close by describing ongoing work toward engineering a high dimensional,
      reversible, low power electronic olfactory sensor which will allow olfactorimotor
      neural circuitry evolved in the virtual world to control an autonomous olfactory
      robot in the physical world. The platform described here is intended to better
      test theories of olfactory circuit function, as well as provide robust odor
      source localization in realistic environments.

PMID- 23112773
TI  - Bio-inspired solutions to the challenges of chemical sensing.

PMID- 23112770
TI  - Self-awareness, self-regulation, and self-transcendence (S-ART): a framework for
      understanding the neurobiological mechanisms of mindfulness.
AB  - Mindfulness-as a state, trait, process, type of meditation, and intervention has
      proven to be beneficial across a diverse group of psychological disorders as well
      as for general stress reduction. Yet, there remains a lack of clarity in the
      operationalization of this construct, and underlying mechanisms. Here, we provide
      an integrative theoretical framework and systems-based neurobiological model that
      explains the mechanisms by which mindfulness reduces biases related to self
      processing and creates a sustainable healthy mind. Mindfulness is described
      through systematic mental training that develops meta-awareness (self-awareness),
      an ability to effectively modulate one's behavior (self-regulation), and a
      positive relationship between self and other that transcends self-focused needs
      and increases prosocial characteristics (self-transcendence). This framework of
      self-awareness, -regulation, and -transcendence (S-ART) illustrates a method for
      becoming aware of the conditions that cause (and remove) distortions or biases.
      The development of S-ART through meditation is proposed to modulate self
      specifying and narrative self-networks through an integrative fronto-parietal
      control network. Relevant perceptual, cognitive, emotional, and behavioral
      neuropsychological processes are highlighted as supporting mechanisms for S-ART,
      including intention and motivation, attention regulation, emotion regulation,
      extinction and reconsolidation, prosociality, non-attachment, and decentering.
      The S-ART framework and neurobiological model is based on our growing
      understanding of the mechanisms for neurocognition, empirical literature, and
      through dismantling the specific meditation practices thought to cultivate
      mindfulness. The proposed framework will inform future research in the
      contemplative sciences and target specific areas for development in the treatment
      of psychological disorders.

PMID- 23112774
TI  - Mechanistic modeling of aberrant energy metabolism in human disease.
AB  - Dysfunction in energy metabolism-including in pathways localized to the
      mitochondria-has been implicated in the pathogenesis of a wide array of
      disorders, ranging from cancer to neurodegenerative diseases to type II diabetes.
      The inherent complexities of energy and mitochondrial metabolism present a
      significant obstacle in the effort to understand the role that these molecular
      processes play in the development of disease. To help unravel these complexities,
      systems biology methods have been applied to develop an array of computational
      metabolic models, ranging from mitochondria-specific processes to genome-scale
      cellular networks. These constraint-based (CB) models can efficiently simulate
      aspects of normal and aberrant metabolism in various genetic and environmental
      conditions. Development of these models leverages-and also provides a powerful
      means to integrate and interpret-information from a wide range of sources
      including genomics, proteomics, metabolomics, and enzyme kinetics. Here, we
      review a variety of mechanistic modeling studies that explore metabolic
      functions, deficiency disorders, and aberrant biochemical pathways in
      mitochondria and related regions in the cell.

PMID- 23112775
TI  - Inhibition of vascular smooth muscle growth via signaling crosstalk between AMP
      activated protein kinase and cAMP-dependent protein kinase.
AB  - Abnormal vascular smooth muscle (VSM) growth is central in the pathophysiology of
      vascular disease yet fully effective therapies to curb this growth are lacking.
      Recent findings from our lab and others support growth control of VSM by
      adenosine monophosphate (AMP)-based approaches including the metabolic sensor AMP
      activated protein kinase (AMPK) and cAMP-dependent protein kinase (PKA).
      Molecular crosstalk between AMPK and PKA has been previously suggested, yet the
      extent to which this occurs and its biological significance in VSM remain
      unclear. Considering their common AMP backbone and similar signaling
      characteristics, we hypothesized that crosstalk exists between AMPK and PKA in
      the regulation of VSM growth. Using rat primary VSM cells (VSMC), the AMPK
      agonist AICAR increased AMPK activity and phosphorylation of the catalytic Thr172
      site on AMPK. Interestingly, AICAR also phosphorylated a suspected PKA-inhibitory
      Ser485 site on AMPK, and these cumulative events were reversed by the PKA
      inhibitor PKI suggesting possible PKA-mediated regulation of AMPK. AICAR also
      increased PKA activity in a reversible fashion. The cAMP stimulator forskolin
      increased PKA activity and completely ameliorated Ser/Thr protein phosphatase-2C
      activity, suggesting a potential mechanism of AMPK modulation by PKA since
      inhibition of PKA by PKI reduced AMPK activity. Functionally, AMPK inhibited
      serum-stimulated cell cycle progression and cellular proliferation; however, PKA
      failed to do so. Moreover, AMPK and PKA reduced PDGF-beta-stimulated VSMC
      migration. Collectively, these results show that AMPK is capable of reducing VSM
      growth in both anti-proliferative and anti-migratory fashion. Furthermore, these
      data suggest that AMPK may be modulated by PKA and that positive feedback may
      exist between these two systems. These findings reveal a discrete nexus between
      AMPK and PKA in VSM and provide basis for metabolically-directed targets in
      reducing pathologic VSM growth.

PMID- 23112776
TI  - Prediction of turn-ends based on anticipation of upcoming words.
AB  - During conversation listeners have to perform several tasks simultaneously. They
      have to comprehend their interlocutor's turn, while also having to prepare their
      own next turn. Moreover, a careful analysis of the timing of natural conversation
      reveals that next speakers also time their turns very precisely. This is possible
      only if listeners can predict accurately when the speaker's turn is going to end.
      But how are people able to predict when a turn-ends? We propose that people know
      when a turn-ends, because they know how it ends. We conducted a gating study to
      examine if better turn-end predictions coincide with more accurate anticipation
      of the last words of a turn. We used turns from an earlier button-press
      experiment where people had to press a button exactly when a turn-ended. We show
      that the proportion of correct guesses in our experiment is higher when a turn's
      end was estimated better in time in the button-press experiment. When people were
      too late in their anticipation in the button-press experiment, they also
      anticipated more words in our gating study. We conclude that people made
      predictions in advance about the upcoming content of a turn and used this
      prediction to estimate the duration of the turn. We suggest an economical model
      of turn-end anticipation that is based on anticipation of words and syntactic
      frames in comprehension.

PMID- 23112777
TI  - Language augmented prediction.

PMID- 23112778
TI  - The role of body-related and environmental sources of knowledge in the
      construction of different conceptual categories.
AB  - CONTROVERSIES EXIST REGARDING: (a) the relationships between perceptual and
      conceptual activities and (b) the format and neuro-anatomical substrates of
      concepts. Some authors maintain that concepts are represented in the brain in a
      propositional, abstract way, which is totally unrelated to the sensory-motor
      functions of the brain. Other authors argue that concepts are represented in the
      same format in which they are constructed by the sensory-motor system and can be
      considered as activity patterns distributed across different perceptual and motor
      domains. The present paper examines two groups of investigations that support the
      second view. Particular attention is given to the role of body movements and
      somatosensory inputs in the representation of artifacts and, respectively, of
      visual and other perceptual sources of knowledge in the construction of
      biological categories. The first group of studies aimed to assess the weight of
      various kinds of information in the representation of different conceptual
      categories by asking normal subjects to subjectively evaluate the role of various
      perceptual, motor, and encyclopedic sources of knowledge in the construction of
      different semantic categories. The second group of studies investigated the neuro
      anatomical correlates of various types of categorical disorders. These last
      investigations showed that the cortical areas damaged in patients with a disorder
      selectively affecting a given category have a critical role in processing the
      information that has contributed most to constructing the affected category. Both
      lines of research suggest that body movements and somatosensory information have
      a major role in the representation of actions and artifacts mainly known through
      manipulations and other actions, whereas visual and other perceptual information
      has a dominant role in the representation of animals and other living things.

PMID- 23112779
TI  - Does attentional selectivity in the flanker task improve discretely or gradually?
AB  - An important question is whether attentional selectivity improves discretely or
      continuously during stimulus processing. In a recent study, Hubner et al. (2010)
      found that the discrete Dual-Stage Two-Phase (DSTP) model accounted better for
      flanker-task data than various continuous-improvement models. However, in a
      subsequent study, White et al. (2011) introduced the continuous shrinking
      spotlight (SSP) model and showed that it was superior to the DSTP model. From
      this result they concluded that attentional selectivity improves continuously
      rather than discretely. Because different stimuli and procedures were used in
      these two studies, though, we questioned that the superiority of the SSP model
      holds generally. Therefore, we fit the SSP model to Hubner et al.'s data and
      found that the DSTP model was again superior. A series of four experiments
      revealed that model superiority depends on the response-stimulus interval.
      Together, our results demonstrate that methodological details can be crucial for
      model selection, and that further comparisons between the models are needed
      before it can be decided whether attentional selectivity improves continuously or
      discretely.

PMID- 23112780
TI  - Anger elicitation in tonga and Germany: the impact of culture on cognitive
      determinants of emotions.
AB  - The cognitive appraisal of an event is crucial for the elicitation and
      differentiation of emotions, and causal attributions are an integral part of this
      process. In an interdisciplinary project comparing Tonga and Germany, we examined
      how cultural differences in attribution tendencies affect emotion assessment and
      elicitation. Data on appraising causality and responsibility and on emotional
      responses were collected through questionnaires based on experimentally designed
      vignettes, and were related to culture-specific values, norms, and the prevailing
      self-concept. The experimental data support our hypothesis that - driven by
      culturally defined self-concepts and corresponding attribution tendencies -
      members of the two cultures cognitively appraise events in diverging manners and
      consequently differ in their emotional responses. Ascription of responsibility to
      self and/or circumstances, in line with a more interdependent self-concept, co
      varies with higher ratings of shame, guilt, and sadness, whereas ascription of
      responsibility to others, in line with a less interdependent self-concept, co
      varies with higher ratings of anger. These findings support the universal
      contingency hypothesis and help to explain cultural differences in this domain on
      a fine-grained level.

PMID- 23112782
TI  - "Distracters" Do Not Always Distract: Visual Working Memory for Angry Faces is
      Enhanced by Incidental Emotional Words.
AB  - We are often required to filter out distraction in order to focus on a primary
      task during which working memory (WM) is engaged. Previous research has shown
      that negative versus neutral distracters presented during a visual WM maintenance
      period significantly impair memory for neutral information. However, the contents
      of WM are often also emotional in nature. The question we address here is how
      incidental information might impact upon visual WM when both this and the memory
      items contain emotional information. We presented emotional versus neutral words
      during the maintenance interval of an emotional visual WM faces task.
      Participants encoded two angry or happy faces into WM, and several seconds into a
      9 s maintenance period a negative, positive, or neutral word was flashed on the
      screen three times. A single neutral test face was presented for retrieval with a
      face identity that was either present or absent in the preceding study array. WM
      for angry face identities was significantly better when an emotional (negative or
      positive) versus neutral (or no) word was presented. In contrast, WM for happy
      face identities was not significantly affected by word valence. These findings
      suggest that the presence of emotion within an intervening stimulus boosts the
      emotional value of threat-related information maintained in visual WM and thus
      improves performance. In addition, we show that incidental events that are
      emotional in nature do not always distract from an ongoing WM task.

PMID- 23112783
TI  - Locomotor Inhibition in Adult Horses Faced to Stressors: A Single Postpartum
      Experience May be Enough!
AB  - Despite the number of postpartum handling that a newborn experiences, few studies
      focus on their long-term consequences. In rats, regular long separations from the
      mother, during the early life, led to modifications of the locomotor activity
      when the animal is confronted to a stressor. In horses, one component of the
      behavioral response to stressful situation is active locomotion. We wondered if
      the routine postpartum handling undergone by foals, would affect their level of
      reactivity or the way they express their stress, when older. One single prolonged
      bout of handling just after birth clearly affected later adult expression of
      stress reactivity. In social separation associated with novelty, handled, and
      unhandled horses produced an equal amount of whinnies, showing a similar vocal
      response to stress. However, both groups differed in their locomotor response to
      the situations. Early handled foals expressed less of the active forms of
      locomotion than the control group. Our findings highlight the need of further
      reflections on long-term effects of routine handlings procedures close to birth.

PMID- 23112784
TI  - Attitudes Toward Assisted Suicide and Life-Prolonging Measures in Swiss ALS
      Patients and Their Caregivers.
AB  - OBJECTIVES: In Switzerland, assisted suicide (AS) is legal, provided that the
      person seeking assistance has decisional capacity and the person assisting is not
      motivated by reasons of self-interest. However, in this particular setting
      nothing is known about patients' and their caregivers' attitudes toward AS and
      life-prolonging measures. METHODS: Data was retrieved through validated
      questionnaires and personal interviews in 33 patients and their caregivers
      covering the following domains: physical function according to the revised
      Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), demographic
      data, quality of life, anxiety, depression, social situation, spirituality,
      burden of disease, life-prolonging, and life-shortening acts. RESULTS: In
      patients the median time after diagnosis was 9 months (2-90) and the median
      Amyotrophic Lateral Sclerosis (ALS) FRS-R score was 37 (22-48). The majority of
      patients (94%; n = 31) had no desire to hasten death. Patients' and caregivers'
      attitudes toward Percutaneous Endoscopic Gastrostomy (PEG) and Non-Invasive
      Ventilation (NIV) differed. Significantly more patients than caregivers (21.2
      versus 3.1%) stated that they were against NIV (p = 0.049) and against PEG (27.3
      versus 3.1%; p = 0.031). Answers regarding tracheotomy were not significantly
      different (p = 0.139). Caregivers scored significantly higher levels of
      "suffering" (p = 0.007), "loneliness" (p = 0.006), and "emotional distress"
      answering the questionnaires (p < 0.001). Suffering (p < 0.026) and loneliness (p
      < 0.016) were related to the score of the Hospital Anxiety and Depression Scale
      (HADS) in patients. CONCLUSION: A liberal legal setting does not necessarily
      promote the wish for AS. However, the desire to discuss AS is prevalent in ALS
      patients. There is a higher level of suffering and loneliness on the caregivers'
      side. A longitudinal study is warranted.

PMID- 23112781
TI  - A review of intentional and cognitive control in autism.
AB  - Different clinical studies have provided empirical evidence for impairments in
      cognitive control in individuals with autism spectrum disorders (ASD). The
      challenge arises, however, when trying to specify the neurocognitive mechanisms
      behind the reported observations of deviant patterns of goal-directed behavior in
      ASD. Studies trying to test specific assumptions by applying designs that are
      based on a more controlled experimental conditions often fail in providing strong
      evidence for an impairment in specific cognitive functions. In this review, we
      summarize and critically reflect on behavioral findings and their theoretical
      explanations regarding cognitive control processing in autism, also from a
      developmental perspective. The specific focus of this review is the recent
      evidence of deficits in intentional control - a specific subset of cognitive
      control processes that biases the choice of our behavioral goals - coming from
      different research fields. We relate this evidence to the cognitive rigidity
      observed in ASD and argue that individuals with ASD experience problems at the
      intentional level rather than at the level of implementation of intentions. Both
      these processes are related to cognitive control mechanisms but in different
      ways. Finally, we discuss new directions in studying cognitive control in ASD and
      how these relate to adaptive cognition.

PMID- 23112785
TI  - Action-effect bindings and ideomotor learning in intention- and stimulus-based
      actions.
AB  - According to ideomotor theory, action-effect associations are crucial for
      voluntary action control. Recently, a number of studies started to investigate
      the conditions that mediate the acquisition and application of action-effect
      associations by comparing actions carried out in response to exogenous stimuli
      (stimulus-based) with actions selected endogenously (intention-based). There is
      evidence that the acquisition and/or application of action-effect associations is
      boosted when acting in an intention-based action mode. For instance,
      bidirectional action-effect associations were diagnosed in a forced choice test
      phase if participants previously experienced action-effect couplings in an
      intention-based but not in a stimulus-based action mode. The present study aims
      at investigating effects of the action mode on action-effect associations in more
      detail. In a series of experiments, we compared the strength and durability of
      short-term action-effect associations (binding) immediately following intention-
      as well as stimulus-based actions. Moreover, long-term action-effect associations
      (learning) were assessed in a subsequent test phase. Our results show short-term
      action-effect associations of equal strength and durability for both action
      modes. However, replicating previous results, long-term associations were
      observed only following intention-based actions. These findings indicate that the
      effect of the action mode on long-term associations cannot merely be a result of
      accumulated short-term action-effect bindings. Instead, only those episodic
      bindings are selectively perpetuated and retrieved that integrate action-relevant
      aspects of the processing event, i.e., in case of intention-based actions, the
      link between action and ensuing effect.

PMID- 23112786
TI  - The end-state comfort effect in 3- to 8-year-old children in two object
      manipulation tasks.
AB  - The aim of the study was to compare 3- to 8-year-old children's propensity to
      anticipate a comfortable hand posture at the end of a grasping movement (end
      state comfort effect) between two different object manipulation tasks, the bar
      transport task, and the overturned-glass task. In the bar-transport task,
      participants were asked to insert a vertically positioned bar into a small
      opening of a box. In the overturned-glass task, participants were asked to put an
      overturned-glass right-side-up on a coaster. Half of the participants experienced
      action effects (lights) as a consequence of their movements (AE groups), while
      the other half of the participants did not (No-AE groups). While there was no
      difference between the AE and No-AE groups, end-state comfort performance
      differed across age as well as between tasks. Results revealed a significant
      increase in end-state comfort performance in the bar-transport task from 13% in
      the 3-year-olds to 94% in the 8-year-olds. Interestingly, the number of children
      grasping the bar according to end-state comfort doubled from 3 to 4 years and
      from 4 to 5 years of age. In the overturned-glass task an increase in end-state
      comfort performance from already 63% in the 3-year-olds to 100% in the 8-year
      olds was significant as well. When comparing end-state comfort performance across
      tasks, results showed that 3- and 4-year-old children were better at manipulating
      the glass as compared to manipulating the bar, most probably, because children
      are more familiar with manipulating glasses. Together, these results suggest that
      preschool years are an important period for the development of motor planning in
      which the familiarity with the object involved in the task plays a significant
      role in children's ability to plan their movements according to end-state
      comfort.

PMID- 23112787
TI  - Instant attraction: immediate action-effect bindings occur for both, stimulus-
      and goal-driven actions.
AB  - Flexible behavior is only possible if contingencies between own actions and
      following environmental effects are acquired as quickly as possible; and recent
      findings indeed point toward an immediate formation of action-effect bindings
      already after a single coupling of an action and its effect. The present study
      explored whether these short-term bindings occur for both, stimulus- and goal
      driven actions ("forced-choice actions" vs. "free-choice actions"). Two
      experiments confirmed that immediate action-effect bindings are formed for both
      types of actions and affect upcoming behavior. These findings support the view
      that action-effect binding is a ubiquitous phenomenon which occurs for any type
      of action.

PMID- 23112788
TI  - Infants generalize representations of statistically segmented words.
AB  - The acoustic variation in language presents learners with a substantial
      challenge. To learn by tracking statistical regularities in speech, infants must
      recognize words across tokens that differ based on characteristics such as the
      speaker's voice, affect, or the sentence context. Previous statistical learning
      studies have not investigated how these types of non-phonemic surface form
      variation affect learning. The present experiments used tasks tailored to two
      distinct developmental levels to investigate the robustness of statistical
      learning to variation. Experiment 1 examined statistical word segmentation in 11
      month-olds and found that infants can recognize statistically segmented words
      across a change in the speaker's voice from segmentation to testing. The
      direction of infants' preferences suggests that recognizing words across a voice
      change is more difficult than recognizing them in a consistent voice. Experiment
      2 tested whether 17-month-olds can generalize the output of statistical learning
      across variation to support word learning. The infants were successful in their
      generalization; they associated referents with statistically defined words
      despite a change in voice from segmentation to label learning. Infants' learning
      patterns also indicate that they formed representations of across word syllable
      sequences during segmentation. Thus, low probability sequences can act as object
      labels in some conditions. The findings of these experiments suggest that the
      units that emerge during statistical learning are not perceptually constrained,
      but rather are robust to naturalistic acoustic variation.

PMID- 23112789
TI  - Difficult diagnoses in hyperkinetic disorders - a focused review.
AB  - Hyperkinesias are heterogeneous conditions that share the feature of production
      of involuntary, abnormal, excessive movements. Tremor, dystonia, and chorea are
      amongst the most common of these phenomena. In this focused review there is a
      discussion of difficult issues in hyperkinesias. The first one is the
      differential diagnosis between essential tremor (ET) and Parkinson's disease
      (PD). They are readily distinguishable in the majority of patients but in a few
      subjects ET coexist with parkinsonian features whose underlying mechanism remains
      to be determined. The second topic of the review is dystonic tremor. Although
      increasingly diagnosed and reported as accounting for the majority of scans
      without evidence of dopaminergic deficits, its diagnostic criteria are ill
      defined and differentiation from PD and ET can be challenging. In the last
      section, there is a discussion of the differential diagnosis of Sydenham's chorea
      (SC), the most common cause of chorea in children. In a few patients, vascular
      disease, systemic lupus erythematosus, and primary antiphospholipid antibody
      syndrome can mimic SC.

PMID- 23112790
TI  - Cognitive impairment and dementia-an update.

PMID- 23112791
TI  - Human quadrupedalism is not an epiphenomenon caused by neurodevelopmental
      malformation and ataxia.
AB  - Two cases with quadrupedal locomotion (QL) were presented. In both cases,
      cognitive and psychiatric functions were normal and, no neurological deficits
      were observed, except for a sequel paralysis of left leg in Case 2. It was
      suggested that human QL (1) should not be considered as an epiphenomenon caused
      by neurodevelopmental malformation and ataxia, but (2) may be considered as a re
      emergence of the ancestral diagonal QL, and (3) it may spontaneously emerge in
      humans with entirely normal brains, by taking advantage of neural networks such
      as central pattern generators that have been preserved for about 400 million
      years.

PMID- 23112792
TI  - Research topic: neurosteroids.

PMID- 23112793
TI  - On the existence and function of galanin receptor heteromers in the central
      nervous system.
AB  - Galanin receptor (GalR) subtypes 1-3 linked to central galanin neurons may form
      heteromers with each other and other types of G protein-coupled receptors in the
      central nervous system (CNS). These heteromers may be one molecular mechanism for
      galanin peptides and their N-terminal fragments (gal 1-15) to modulate the
      function of different types of glia-neuronal networks in the CNS, especially the
      emotional and the cardiovascular networks. GalR-5-HT1A heteromers likely exist
      with antagonistic GalR-5-HT1A receptor-receptor interactions in the ascending
      midbrain raphe 5-HT neuron systems and their target regions. They represent a
      novel target for antidepressant drugs. Evidence is given for the existence of
      GalR1-5-HT1A heteromers in cellular models with trans-inhibition of the protomer
      signaling. A GalR1-GalR2 heteromer is proposed to be a galanin N-terminal
      fragment preferring receptor (1-15) in the CNS. Furthermore, a GalR1-GalR2-5-HT1A
      heterotrimer is postulated to explain why only galanin (1-15) but not galanin (1
      29) can antagonistically modulate the 5-HT1A receptors in the dorsal hippocampus
      rich in gal fragment binding sites. The results underline a putative role of
      different types of GalR-5-HT1A heteroreceptor complexes in depression. GalR
      antagonists may also have therapeutic actions in depression by blocking the
      antagonistic GalR-NPYY1 receptor interactions in putative GalR-NPYY1 receptor
      heteromers in the CNS resulting in increases in NPYY1 transmission and
      antidepressant effects. In contrast the galanin fragment receptor (a postulated
      GalR1-GalR2 heteromer) appears to be linked to the NPYY2 receptor enhancing the
      affinity of the NPYY2 binding sites in a putative GalR1-GalR2-NPYY2 heterotrimer.
      Finally, putative GalR-alpha2-adrenoreceptor heteromers with antagonistic
      receptor-receptor interactions may be a widespread mechanism in the CNS for
      integration of galanin and noradrenaline signals also of likely relevance for
      depression.

PMID- 23112794
TI  - Synthetic feedback loop model for increasing microbial biofuel production using a
      biosensor.
AB  - Current biofuel production methods use engineered bacteria to break down
      cellulose and convert it to biofuel. A major challenge in microbial fuel
      production is that increasing biofuel yields can be limited by the toxicity of
      the biofuel to the organism that is producing it. Previous research has
      demonstrated that efflux pumps are effective at increasing tolerance to various
      biofuels. However, when overexpressed, efflux pumps burden cells, which hinders
      growth and slows biofuel production. Therefore, the toxicity of the biofuel must
      be balanced with the toxicity of pump overexpression. We have developed a
      mathematical model for cell growth and biofuel production that implements a
      synthetic feedback loop using a biosensor to control efflux pump expression. In
      this way, the production rate will be maximal when the concentration of biofuel
      is low because the cell does not expend energy expressing efflux pumps when they
      are not needed. Additionally, the microbe is able to adapt to toxic conditions by
      triggering the expression of efflux pumps, which allow it to continue biofuel
      production. Sensitivity analysis indicates that the feedback sensor model is
      insensitive to many system parameters, but a few key parameters can influence
      growth and production. In comparison to systems that express efflux pumps at a
      constant level, the feedback sensor increases overall biofuel production by
      delaying pump expression until it is needed. This result is more pronounced when
      model parameters are variable because the system can use feedback to adjust to
      the actual rate of biofuel production.

PMID- 23112795
TI  - Metagenome Analysis of a Complex Community Reveals the Metabolic Blueprint of
      Anammox Bacterium "Candidatus Jettenia asiatica".
AB  - Anaerobic ammonium-oxidizing (anammox) bacteria are key players in the global
      nitrogen cycle and responsible for significant global nitrogen loss. Moreover,
      the anammox process is widely implemented for nitrogen removal from wastewaters
      as a cost-effective and environment-friendly alternative to conventional
      nitrification-denitrification systems. Currently, five genera of anammox bacteria
      have been identified, together forming a deep-branching order in the
      Planctomycetes-Verrucomicrobium-Chlamydiae superphylum. Members of all genera
      have been detected in wastewater treatment plants and have been enriched in lab
      scale bioreactors, but genome information is not yet available for all genera.
      Here we report the metagenomic analysis of a granular sludge anammox reactor
      dominated (~50%) by "Candidatus Jettenia asiatica." The metagenome was sequenced
      using both Illumina and 454 pyrosequencing. After de novo assembly 37,432 contigs
      with an average length of 571 nt were obtained. The contigs were then analyzed by
      BLASTx searches against the protein sequences of "Candidatus Kuenenia
      stuttgartiensis" and a set of 25 genes essential in anammox metabolism were
      detected. Additionally all reads were mapped to the genome of an anammox strain
      KSU-1 and de novo assembly was performed again using the reads that could be
      mapped on KSU-1. Using this approach, a gene encoding copper-containing nitrite
      reductase NirK was identified in the genome, instead of cytochrome cd(1)-type
      nitrite reductase (NirS, present in "Ca. Kuenenia stuttgartiensis" and "Ca.
      Scalindua profunda"). Finally, the community composition was investigated through
      MetaCluster analysis, 16S rRNA gene analysis and read mapping, which showed the
      presence of other important community members such as aerobic ammonia-oxidizing
      bacteria, methanogens, and the denitrifying methanotroph "Ca. Methylomirabilis
      oxyfera", indicating a possible active methane and nitrogen cycle in the
      bioreactor under the prevailing operational conditions.

PMID- 23112796
TI  - Denitrification and environmental factors influencing nitrate removal in Guaymas
      Basin hydrothermally altered sediments.
AB  - We measured potential nitrate removal and denitrification rates in hydrothermally
      altered sediments inhabited by Beggiatoa mats and adjacent brown oil stained
      sediments from the Guaymas Basin, Gulf of California. Sediments with Beggiatoa
      maintained slightly higher rates of potential denitrification than did brown
      sediments at 31.2 +/- 12.1 versus 21.9 +/- 1.4 uM N day(-1), respectively. In
      contrast, the nitrate removal rates in brown sediments were higher than those
      observed in mat-hosting sediments at 418 +/- 145 versus 174 +/- 74 uM N day(-1),
      respectively. Additional experiments were conducted to assess the responses of
      denitrifying communities to environmental factors [i.e., nitrate, sulfide, and
      dissolved organic carbon (DOC) concentration)]. The denitrifying community had a
      high affinity for nitrate (K(m) = 137 +/- 91 uM NO3-), in comparison to other
      environmental communities of denitrifiers, and was capable of high maximum rates
      of denitrification (V(max) = 1164 +/- 153 uM N day(-1)). The presence of sulfide
      resulted in significantly lower denitrification rates. Microorganisms with the
      potential to perform denitrification were assessed in these sediments using the
      bacterial 16S rRNA gene and nitrous oxide reductase (nosZ) functional gene
      libraries. The bacterial 16S rRNA gene clone library was dominated by
      Epsilonproteobacteria (38%), some of which (e.g., Sulfurimonas sp.) have a
      potential for sulfide-dependent denitrification. The nosZ clone library did not
      contain clones similar to pure culture denitrifiers; these clones were most
      closely associated with environmental clones.

PMID- 23112797
TI  - Elemental and fatty acid composition of snow algae in Arctic habitats.
AB  - Red, orange or green snow is the macroscopic phenomenon comprising different
      eukaryotic algae. Little is known about the ecology and nutrient regimes in these
      algal communities. Therefore, eight snow algal communities from five intensively
      tinted snow fields in western Spitsbergen were analysed for nutrient
      concentrations and fatty acid (FA) composition. To evaluate the importance of a
      shift from green to red forms on the FA-variability of the field samples, four
      snow algal strains were grown under nitrogen replete and moderate light (+N+ML)
      or N-limited and high light (-N+HL) conditions. All eight field algal communities
      were dominated by red and orange cysts. Dissolved nutrient concentration of the
      snow revealed a broad range of NH(+) (4) (<0.005-1.2 mg N l(-1)) and only low
      PO(3-) (4) (<18 MUg P l(-1)) levels. The external nutrient concentration did not
      reflect cellular nutrient ratios as C:N and C:P ratios of the communities were
      highest at locations containing relatively high concentrations of NH(+) (4) and
      PO(3-) (4). Molar N:P ratios ranged from 11 to 21 and did not suggest clear
      limitation of a single nutrient. On a per carbon basis, we found a 6-fold
      difference in total FA content between the eight snow algal communities, ranging
      from 50 to 300 mg FA g C(-1). In multivariate analyses total FA content opposed
      the cellular N:C quota and a large part of the FA variability among field
      locations originated from the abundant FAs C18:1n-9, C18:2n-6, and C18:3n-3. Both
      field samples and snow algal strains grown under -N+HL conditions had high
      concentrations of C18:1n-9. FAs possibly accumulated due to the cessation of
      growth. Differences in color and nutritional composition between patches of snow
      algal communities within one snow field were not directly related to nutrient
      conditions. We propose that the highly patchy distribution of snow algae within
      and between snow fields may also result from differences in topographical and
      geological parameters such as slope, melting water rivulets, and rock formation.

PMID- 23112798
TI  - From biomarkers to a clue of biology: a computation-aided perspective of immune
      gene expression profiles in human type 1 diabetes.
AB  - Dysregulated expression of key immune genes may cause breakdown of immunological
      tolerance and development of autoimmune disorders such as type 1 diabetes (T1D).
      General immune insufficiencies have also been implicated as a trigger of
      autoimmunity, due to their potential impact on immune homeostasis. Recent studies
      have detected evidence of systemic reduction in immune gene expression in long
      term diabetic patients but the changes were not present before or at T1D onset.
      The changes could not be merely correlated with alteration in metabolic
      parameters. The studies also identified a dynamic expression pattern of several
      well-known as well as little-studied, immune-related genes during the course of
      T1D. An intriguing "ratio profile" of immune regulatory genes, such as CTLA4 and
      members of the S100 family, versus "baseline" immune genes, such as CD3G,
      prompted us to further examine immune gene expression relationships for a set of
      molecules representing T cells, B cells, and myeloid cells. No evidence was found
      to suggest an overall breach of tolerance equilibrium in T1D. Perplexingly,
      patients with long-term T1D presented a gene expression profile that was
      surprisingly more coordinated in analyses of "networking" relationship.
      Computational analyses of the "ratio profiles" or "relationship profiles" of
      immune gene expression might provide a clue for further studies of immunobiology
      in human T1D and other autoimmune diseases, as to how the profiles may be related
      to the pathogenic cause of the disease, to the effect of the diseases on immune
      homeostasis, or to an immunological process associated with the course of the
      diseases but is neither a direct cause nor a direct effect of the diseases.

PMID- 23112800
TI  - Antimicrobial peptides: utility players in innate immunity.

PMID- 23112799
TI  - TIR8/SIGIRR is an Interleukin-1 Receptor/Toll Like Receptor Family Member with
      Regulatory Functions in Inflammation and Immunity.
AB  - Interleukin-1R like receptors (ILRs) and Toll Like Receptors (TLRs) are key
      receptors of innate immunity, inflammation, and orientation of the adaptive
      response. They belong to a superfamily characterized by the presence of a
      conserved intracellular domain, the Toll/IL-1R (TIR) domain, which is involved in
      the activation of a signaling cascade leading to activation of transcription
      factors associated to inflammation. The activation of inflammatory responses and
      immunity by ILRs or TLRs signaling is potentially detrimental for the host in
      acute and chronic conditions and is tightly regulated at different levels by
      receptor antagonists, decoy receptors or signaling molecules, and miRNAs. Recent
      evidence suggests that the ILRs family member TIR8 (also known as SIGIRR) is a
      regulatory protein acting intracellularly to inhibit ILRs and TLRs signaling. In
      particular, current evidence suggests that TIR8/SIGIRR dampens TLRs-mediated
      activation and inhibits signaling receptor complexes of IL-1 family members
      associated with Th1 (IL-18), Th2 (IL-33), and Th17 (IL-1) differentiation.
      Studies with Tir8/Sigirr-deficient mice showed that the ability to dampen
      signaling from ILRs and TLRs family members makes TIR8/SIGIRR a key regulator of
      inflammation. Here, we summarize our current understanding of the structure and
      function of TIR8/SIGIRR, focusing on its role in different pathological
      conditions, ranging from infectious and sterile inflammation, to autoimmunity and
      cancer-related inflammation.

PMID- 23112801
TI  - Evidence for a Contribution of ALA Synthesis to Plastid-To-Nucleus Signaling.
AB  - The formation of 5-aminolevulinic acid (ALA) in tetrapyrrole biosynthesis is
      widely controlled by environmental and metabolic feedback cues that determine the
      influx into the entire metabolic path. Because of its central role as the rate
      limiting step, we hypothesized a potential role of ALA biosynthesis in
      tetrapyrrole-mediated retrograde signaling and exploited the direct impact of ALA
      biosynthesis on nuclear gene expression (NGE) by using two different approaches.
      Firstly, the Arabidopsisgun1, hy1 (gun2), hy2 (gun3), gun4 mutants showing
      uncoupled NGE from the physiological state of chloroplasts were thoroughly
      examined for regulatory modifications of ALA synthesis and transcriptional
      control in the nucleus. We found that reduced ALA-synthesizing capacity is common
      to analyzed gun mutants. Inhibition of ALA synthesis by gabaculine (GAB) that
      inactivates glutamate-1-semialdehyde aminotransferase and ALA feeding of wild
      type and mutant seedlings corroborate the expression data of gun mutants.
      Transcript level of photosynthetic marker genes were enhanced in norflurazon (NF)
      treated seedlings upon additional GAB treatment, while enhanced ALA amounts
      diminish these RNA levels in NF-treated wild-type in comparison to the solely NF
      treated seedlings. Secondly, the impact of posttranslationally down-regulated ALA
      synthesis on NGE was investigated by global transcriptome analysis of GAB-treated
      Arabidopsis seedlings and the gun4-1 mutant, which is also characterized by
      reduced ALA formation. A common set of significantly modulated genes was
      identified indicating ALA synthesis as a potential signal emitter. The over
      represented gene ontology categories of genes with decreased or increased
      transcript abundance highlight a few biological processes and cellular functions,
      which are remarkably affected in response to plastid-localized ALA biosynthesis.
      These results support the hypothesis that ALA biosynthesis correlates with
      retrograde signaling-mediated control of NGE.

PMID- 23112802
TI  - Quinolizidine alkaloid biosynthesis: recent advances and future prospects.
AB  - Lys-derived alkaloids, including piperidine, quinolizidine, indolizidine, and
      lycopodium alkaloids, are widely distributed throughout the plant kingdom.
      Several of these alkaloids have beneficial properties for humans and have been
      used in medicine. However, the molecular mechanisms underlying the biosynthesis
      of these alkaloids are not well understood. In the present article, we discuss
      recent advances in our understanding of Lys-derived alkaloids, especially the
      biochemistry, molecular biology, and biotechnology of quinolizidine alkaloid (QA)
      biosynthesis. We have also highlighted Lys decarboxylase (LDC), the enzyme that
      catalyzes the first committed step of QA biosynthesis and answers a longstanding
      question about the molecular entity of LDC activity in plants. Further prospects
      using current advanced technologies, such as next-generation sequencing, in
      medicinal plants have also been discussed.

PMID- 23112803
TI  - Mining and visualization of microarray and metabolomic data reveal extensive cell
      wall remodeling during winter hardening in Sitka spruce (Picea sitchensis).
AB  - Microarray gene expression profiling is a powerful technique to understand
      complex developmental processes, but making biologically meaningful inferences
      from such studies has always been challenging. We previously reported a
      microarray study of the freezing acclimation period in Sitka spruce (Picea
      sitchensis) in which a large number of candidate genes for climatic adaptation
      were identified. In the current paper, we apply additional systems biology tools
      to these data to further probe changes in the levels of genes and metabolites and
      activities of associated pathways that regulate this complex developmental
      transition. One aspect of this adaptive process that is not well understood is
      the role of the cell wall. Our data suggest coordinated metabolic and signaling
      responses leading to cell wall remodeling. Co-expression of genes encoding
      proteins associated with biosynthesis of structural and non-structural cell wall
      carbohydrates was observed, which may be regulated by ethylene signaling
      components. At the same time, numerous genes, whose products are putatively
      localized to the endomembrane system and involved in both the synthesis and
      trafficking of cell wall carbohydrates, were up-regulated. Taken together, these
      results suggest a link between ethylene signaling and biosynthesis, and targeting
      of cell wall related gene products during the period of winter hardening.
      Automated Layout Pipeline for Inferred NEtworks (ALPINE), an in-house plugin for
      the Cytoscape visualization environment that utilizes the existing GeneMANIA and
      Mosaic plugins, together with the use of visualization tools, provided images of
      proposed signaling processes that became active over the time course of winter
      hardening, particularly at later time points in the process. The resulting
      visualizations have the potential to reveal novel, hypothesis-generating, gene
      association patterns in the context of targeted subcellular location.

PMID- 23112804
TI  - Measured, modeled, and causal conceptions of fitness.
AB  - THIS PAPER PROPOSES PARTIAL ANSWERS TO THE FOLLOWING QUESTIONS: in what senses
      can fitness differences plausibly be considered causes of evolution?What
      relationships are there between fitness concepts used in empirical research,
      modeling, and abstract theoretical proposals? How does the relevance of different
      fitness concepts depend on research questions and methodological constraints? The
      paper develops a novel taxonomy of fitness concepts, beginning with type fitness
      (a property of a genotype or phenotype), token fitness (a property of a
      particular individual), and purely mathematical fitness. Type fitness includes
      statistical type fitness, which can be measured from population data, and
      parametric type fitness, which is an underlying property estimated by statistical
      type fitnesses. Token fitness includes measurable token fitness, which can be
      measured on an individual, and tendential token fitness, which is assumed to be
      an underlying property of the individual in its environmental circumstances. Some
      of the paper's conclusions can be outlined as follows: claims that fitness
      differences do not cause evolution are reasonable when fitness is treated as
      statistical type fitness, measurable token fitness, or purely mathematical
      fitness. Some of the ways in which statistical methods are used in population
      genetics suggest that what natural selection involves are differences in
      parametric type fitnesses. Further, it's reasonable to think that differences in
      parametric type fitness can cause evolution. Tendential token fitnesses, however,
      are not themselves sufficient for natural selection. Though parametric type
      fitnesses are typically not directly measurable, they can be modeled with purely
      mathematical fitnesses and estimated by statistical type fitnesses, which in turn
      are defined in terms of measurable token fitnesses. The paper clarifies the ways
      in which fitnesses depend on pragmatic choices made by researchers.

PMID- 23112805
TI  - AhR activation underlies the CYP1A autoinduction by A-998679 in rats.
AB  - Xenobiotic-mediated induction of cytochrome P450 (CYP) drug metabolizing enzymes
      (DMEs) is frequently encountered in drug discovery and can influence disposition,
      pharmacokinetic, and toxicity profiles. The CYP1A subfamily of DMEs plays a
      central role in the biotransformation of several drugs and environmental
      chemicals. Autoinduction of drugs through CYP3A enzymes is a common mechanism for
      their enhanced clearance. However, autoinduction via CYP1A is encountered less
      frequently. In this report, an experimental compound, A-998679 [3-(5-pyridin-3-yl
      1,2,4-oxadiazol-3-yl) benzonitrile], was shown to enhance its own clearance via
      induction of Cyp1a1 and Cyp1a2. Rats were dosed for 5 days with 30, 100, and 200
      mg/kg/day A-998679. During the dosing period, the compound's plasma AUC decreased
      at 30 mg/kg (95%) and 100 mg/kg (80%). Gene expression analysis and
      immunohistochemistry of the livers showed a large increase in the mRNA and
      protein levels of Cyp1a, which was involved in the biotransformation of A-998679.
      Induction of CYP1A was confirmed in primary rat, human, and dog hepatocytes. The
      compound also weakly inhibited CYP1A2 in human liver microsomes. A-998679
      activated the aryl hydrocarbon receptor (AhR) in a luciferase gene reporter assay
      in HepG2 cells, upregulated expression of genes associated with AhR activation in
      rat liver and enhanced nuclear migration of AhR in HepG2 cells. Collectively
      these results demonstrate that A-998679 is an AhR activator that induces Cyp1a1
      and Cyp1a2 expression, resulting in an autoinduction phenomenon. The unique
      properties of A-998679, along with its novel structure distinct from classical
      polycyclic aromatic hydrocarbons (PAHs), may warrant its further evaluation as a
      tool compound for use in studies involving AhR biology and CYP1A-related
      mechanisms of drug metabolism and toxicity.

PMID- 23112807
TI  - Can we vaccinate against Type 1 diabetes?
AB  - Vaccination is the administration of antigenic material to stimulate the immune
      system to develop adaptive immunity to a disease. As the most successful
      prophylactic in medical history, there is now an emerging interest as to whether
      vaccination can be applied in autoimmune and inflammatory conditions. These are
      diseases of failed immune regulation; vaccination in this context aims to exploit
      the power of antigenic material to stimulate immune homeostasis in the form of
      active, adaptive, regulatory immune responses. Type 1 diabetes is an autoimmune
      disease that could benefit from the therapeutic potential of vaccination. The
      major conditions necessary to make prophylaxis feasible are in place; the self
      antigens are known, the failure of existing immune regulation has been
      demonstrated, early studies of vaccine approaches have proved safe, and the
      preclinical prodrome of the disease can be easily detected by simple blood tests.
      Challenges for future implementation include finding the best mode of delivery
      and the best blend of adjunctive therapies that create the favorable conditions
      required for a vaccine to be effective.

PMID- 23112808
TI  - An emerging concept of vascular salt sensitivity.
AB  - Excessive amounts of salt in food, as usually consumed worldwide, affect the
      vascular system, leading to high blood pressure and premature disabilities. Salt
      entering the vascular bed after a salty meal is transiently bound to the
      endothelial glycocalyx, a negatively charged biopolymer lining the inner surface
      of the blood vessels. This barrier protects the endothelium against salt
      overload. A poorly-developed glycocalyx increases the salt permeability of the
      vascular system and the amount of salt being deposited in the body, which affects
      organ function. A simple test system is now available that evaluates vascular
      salt sensitivity in humans and identifies individuals who are at risk of salt
      induced hypertension. This short review aims to discuss how the underlying basic
      research can be translated into medical practice and, thus, meaningful health
      outcomes.

PMID- 23112809
TI  - Mutual information rate and bounds for it.
AB  - The amount of information exchanged per unit of time between two nodes in a
      dynamical network or between two data sets is a powerful concept for analysing
      complex systems. This quantity, known as the mutual information rate (MIR), is
      calculated from the mutual information, which is rigorously defined only for
      random systems. Moreover, the definition of mutual information is based on
      probabilities of significant events. This work offers a simple alternative way to
      calculate the MIR in dynamical (deterministic) networks or between two time
      series (not fully deterministic), and to calculate its upper and lower bounds
      without having to calculate probabilities, but rather in terms of well known and
      well defined quantities in dynamical systems. As possible applications of our
      bounds, we study the relationship between synchronisation and the exchange of
      information in a system of two coupled maps and in experimental networks of
      coupled oscillators.

PMID- 23112806
TI  - Neuronal responses to physiological stress.
AB  - Physiological stress can be defined as any external or internal condition that
      challenges the homeostasis of a cell or an organism. It can be divided into three
      different aspects: environmental stress, intrinsic developmental stress, and
      aging. Throughout life all living organisms are challenged by changes in the
      environment. Fluctuations in oxygen levels, temperature, and redox state for
      example, trigger molecular events that enable an organism to adapt, survive, and
      reproduce. In addition to external stressors, organisms experience stress
      associated with morphogenesis and changes in inner chemistry during normal
      development. For example, conditions such as intrinsic hypoxia and oxidative
      stress, due to an increase in tissue mass, have to be confronted by developing
      embryos in order to complete their development. Finally, organisms face the
      challenge of stochastic accumulation of molecular damage during aging that
      results in decline and eventual death. Studies have shown that the nervous system
      plays a pivotal role in responding to stress. Neurons not only receive and
      process information from the environment but also actively respond to various
      stresses to promote survival. These responses include changes in the expression
      of molecules such as transcription factors and microRNAs that regulate stress
      resistance and adaptation. Moreover, both intrinsic and extrinsic stresses have a
      tremendous impact on neuronal development and maintenance with implications in
      many diseases. Here, we review the responses of neurons to various physiological
      stressors at the molecular and cellular level.

PMID- 23112810
TI  - Extremely rare interbreeding events can explain neanderthal DNA in living humans.
AB  - Considering the recent experimental discovery of Green et al that present-day non
      Africans have 1 to [Formula: see text] of their nuclear DNA of Neanderthal
      origin, we propose here a model which is able to quantify the genetic
      interbreeding between two subpopulations with equal fitness, living in the same
      geographic region. The model consists of a solvable system of deterministic
      ordinary differential equations containing as a stochastic ingredient a
      realization of the neutral Wright-Fisher process. By simulating the stochastic
      part of the model we are able to apply it to the interbreeding of the African
      ancestors of Eurasians and Middle Eastern Neanderthal subpopulations and estimate
      the only parameter of the model, which is the number of individuals per
      generation exchanged between subpopulations. Our results indicate that the amount
      of Neanderthal DNA in living non-Africans can be explained with maximum
      probability by the exchange of a single pair of individuals between the
      subpopulations at each 77 generations, but larger exchange frequencies are also
      allowed with sizeable probability. The results are compatible with a long
      coexistence time of 130,000 years, a total interbreeding population of order
      [Formula: see text] individuals, and with all living humans being descendants of
      Africans both for mitochondrial DNA and Y chromosome.

PMID- 23112811
TI  - Covalent modification of mutant rat P2X2 receptors with a thiol-reactive
      fluorophore allows channel activation by zinc or acidic pH without ATP.
AB  - Rat P2X2 receptors open at an undetectably low rate in the absence of ATP.
      Furthermore, two allosteric modulators, zinc and acidic pH, cannot by themselves
      open these channels. We describe here the properties of a mutant receptor, K69C,
      before and after treatment with the thiol-reactive fluorophore Alexa Fluor 546
      C(5)-maleimide (AM546). Xenopus oocytes expressing unmodified K69C were not
      activated under basal conditions nor by 1,000 uM ATP. AM546 treatment caused a
      small increase in the inward holding current which persisted on washout and
      control experiments demonstrated this current was due to ATP independent opening
      of the channels. Following AM546 treatment, zinc (100 uM) or acidic external
      solution (pH 6.5) elicited inward currents when applied without any exogenous
      ATP. In the double mutant K69C/H319K, zinc elicited much larger inward currents,
      while acidic pH generated outward currents. Suramin, which is an antagonist of
      wild type receptors, behaved as an agonist at AM546-treated K69C receptors.
      Several other cysteine-reactive fluorophores tested on K69C did not cause these
      changes. These modified receptors show promise as a tool for studying the
      mechanisms of P2X receptor activation.

PMID- 23112812
TI  - Factor structure underlying components of allostatic load.
AB  - Allostatic load is a commonly used metric of health risk based on the hypothesis
      that recurrent exposure to environmental demands (e.g., stress) engenders a
      progressive dysregulation of multiple physiological systems. Prominent indicators
      of response to environmental challenges, such as stress-related hormones,
      sympatho-vagal balance, or inflammatory cytokines, comprise primary allostatic
      mediators. Secondary mediators reflect ensuing biological alterations that
      accumulate over time and confer risk for clinical disease but overlap
      substantially with a second metric of health risk, the metabolic syndrome.
      Whether allostatic load mediators covary and thus warrant treatment as a unitary
      construct remains to be established and, in particular, the relation of
      allostatic load parameters to the metabolic syndrome requires elucidation. Here,
      we employ confirmatory factor analysis to test: 1) whether a single common factor
      underlies variation in physiological systems associated with allostatic load; and
      2) whether allostatic load parameters continue to load on a single common factor
      if a second factor representing the metabolic syndrome is also modeled.
      Participants were 645 adults from Allegheny County, PA (30-54 years old, 82% non
      Hispanic white, 52% female) who were free of confounding medications. Model
      fitting supported a single, second-order factor underlying variance in the
      allostatic load components available in this study (metabolic, inflammatory and
      vagal measures). Further, this common factor reflecting covariation among
      allostatic load components persisted when a latent factor representing metabolic
      syndrome facets was conjointly modeled. Overall, this study provides novel
      evidence that the modeled allostatic load components do share common variance as
      hypothesized. Moreover, the common variance suggests the existence of statistical
      coherence above and beyond that attributable to the metabolic syndrome.

PMID- 23112813
TI  - Characterizing the network of drugs and their affected metabolic subpathways.
AB  - A fundamental issue in biology and medicine is illustration of the overall drug
      impact which is always the consequence of changes in local regions of metabolic
      pathways (subpathways). To gain insights into the global relationship between
      drugs and their affected metabolic subpathways, we constructed a drug-metabolic
      subpathway network (DRSN). This network included 3925 significant drug-metabolic
      subpathway associations representing drug dual effects. Through analyses based on
      network biology, we found that if drugs were linked to the same subpathways in
      the DRSN, they tended to share the same indications and side effects.
      Furthermore, if drugs shared more subpathways, they tended to share more side
      effects. We then calculated the association score by integrating drug-affected
      subpathways and disease-related subpathways to quantify the extent of the
      associations between each drug class and disease class. The results showed some
      close drug-disease associations such as sex hormone drugs and cancer suggesting
      drug dual effects. Surprisingly, most drugs displayed close associations with
      their side effects rather than their indications. To further investigate the
      mechanism of drug dual effects, we classified all the subpathways in the DRSN
      into therapeutic and non-therapeutic subpathways representing drug therapeutic
      effects and side effects. Compared to drug side effects, the therapeutic effects
      tended to work through tissue-specific genes and these genes tend to be expressed
      in the adrenal gland, liver and kidney; while drug side effects always occurred
      in the liver, bone marrow and trachea. Taken together, the DRSN could provide
      great insights into understanding the global relationship between drugs and
      metabolic subpathways.

PMID- 23112814
TI  - Financial stress and outcomes after acute myocardial infarction.
AB  - BACKGROUND: Little is known about the association between financial stress and
      health care outcomes. Our objective was to examine the association between self
      reported financial stress during initial hospitalization and long-term outcomes
      after acute myocardial infarction (AMI). MATERIALS AND METHODS: We used
      prospective registry evaluating myocardial infarction: Event and Recovery
      (PREMIER) data, an observational, multicenter US study of AMI patients discharged
      between January 2003 and June 2004. Primary outcomes were disease-specific and
      generic health status outcomes at 1 year (symptoms, function, and quality of life
      (QoL)), assessed by the Seattle Angina Questionnaire [SAQ] and Short Form [SF]
      12. Secondary outcomes included 1-year rehospitalization and 4-year mortality.
      Hierarchical regression models accounted for patient socio-demographic, clinical,
      and quality of care characteristics, and access and barriers to care. RESULTS:
      Among 2344 AMI patients, 1241 (52.9%) reported no financial stress, 735 (31.4%)
      reported low financial stress, and 368 (15.7%) reported high financial stress.
      When comparing individuals reporting low financial stress to no financial stress,
      there were no significant differences in post-AMI outcomes. In contrast,
      individuals reporting high financial stress were more likely to have worse
      physical health (SF-12 PCS mean difference -3.24, 95% Confidence Interval [CI]: 
      4.82, -1.66), mental health (SF-12 MCS mean difference: -2.44, 95% CI: -3.83, 
      1.05), disease-specific QoL (SAQ QoL mean difference: -6.99, 95% CI: -9.59, 
      4.40), and be experiencing angina (SAQ Angina Relative Risk = 1.66, 95%CI: 1.19,
      2.32) at 1 year post-AMI. While 1-year readmission rates were increased (Hazard
      Ratio = 1.50; 95%CI: 1.20, 1.86), 4-year mortality was no different. CONCLUSIONS:
      High financial stress is common and an important risk factor for worse long-term
      outcomes post-AMI, independent of access and barriers to care.

PMID- 23112815
TI  - Hyperdiversity of genes encoding integral light-harvesting proteins in the
      dinoflagellate Symbiodinium sp.
AB  - The superfamily of light-harvesting complex (LHC) proteins is comprised of
      proteins with diverse functions in light-harvesting and photoprotection. LHC
      proteins bind chlorophyll (Chl) and carotenoids and include a family of LHCs that
      bind Chl a and c. Dinophytes (dinoflagellates) are predominantly Chl c binding
      algal taxa, bind peridinin or fucoxanthin as the primary carotenoid, and can
      possess a number of LHC subfamilies. Here we report 11 LHC sequences for the
      chlorophyll a-chlorophyll c(2)-peridinin protein complex (acpPC) subfamily
      isolated from Symbiodinium sp. C3, an ecologically important peridinin binding
      dinoflagellate taxa. Phylogenetic analysis of these proteins suggests the acpPC
      subfamily forms at least three clades within the Chl a/c binding LHC family;
      Clade 1 clusters with rhodophyte, cryptophyte and peridinin binding
      dinoflagellate sequences, Clade 2 with peridinin binding dinoflagellate sequences
      only and Clades 3 with heterokontophytes, fucoxanthin and peridinin binding
      dinoflagellate sequences.

PMID- 23112816
TI  - Mortality rates across 25-hydroxyvitamin D (25[OH]D) levels among adults with and
      without estimated glomerular filtration rate <60 ml/min/1.73 m2: the third
      national health and nutrition examination survey.
AB  - BACKGROUND: Previous studies exploring the association between 25[OH]D levels and
      mortality in adults with and without kidney disease utilized 25[OH]D thresholds
      that have recently been scrutinized by the Institute of Medicine Committee to
      Review Dietary References Intakes for Vitamin D and Calcium. OBJECTIVE: We
      explored all-cause mortality rates across the spectrum of 25[OH]D levels over an
      eighteen-year follow-up among adults with and without an estimated glomerular
      filtration rate (eGFR) <60 ml/min/1.73 m(2). DESIGN: The study included 1,097
      U.S. adults with eGFR <60 ml/min/1.73 m(2) and 14, 002 adults with eGFR >=60
      ml/min/1.73 m(2). Mortality rates and rate ratios (RR) across 25[OH]D groups were
      calculated with Poisson regression and restricted cubic splines while adjusting
      for covariates. RESULTS: Prevalence of 25[OH]D levels <30 and <20 ng/ml among
      adults with eGFR <60 ml/min/1.73 m(2) was 76.5% (population estimate 6.2 million)
      and 35.4% (population estimate 2.9 million), respectively. Among adults with eGFR
      >= 60 ml/min/1.73 m(2), 70.5% had 25[OH]D levels <30 ng/ml (population estimate
      132.2 million) while 30.3% had 25[OH]D levels <20 ng/ml (population estimate 56.8
      million). Significantly higher mortality rates were noted among individuals with
      25[OH]D levels <12 ng/ml compared to referent group (24 to <30 ng/ml): RR1.41
      (95% CI 1.17, 1.71) among individuals with eGFR <60 ml/min/1.73 m(2) and RR 1.32
      (95% CI 1.13, 1.56) among individuals with eGFR >= 60 ml/min/1.73 m(2) after
      adjustment for covariates including co-morbid conditions. Mortality rates were
      fairly similar across all 25[OH]D groups with levels >20 ng/ml after adjustment
      for all covariates. CONCLUSIONS: Regardless of presence of eGFR <60 ml/min/1.73
      m(2), mortality rates across groups with 25[OH]D levels 20-40 ng/ml are similar.

PMID- 23112817
TI  - A metapopulation model to assess the capacity of spread of meticillin-resistant
      Staphylococcus aureus ST398 in humans.
AB  - The emergence of the livestock-associated clone of meticillin-resistant
      Staphylococcus aureus (MRSA) ST398 is a serious public health issue throughout
      Europe. In The Netherlands a stringent 'search-and-destroy' policy has been
      adopted, keeping low the level of MRSA prevalence. However, reports have recently
      emerged of transmission events between humans showing no links to livestock,
      contradicting belief that MRSA ST398 is poorly transmissible in humans. The
      question regarding the transmissibility of MRSA ST398 in humans therefore remains
      of great interest. Here, we investigated the capacity of MRSA ST398 to spread
      into an entirely susceptible human population subject to the effect of a single
      MRSA-positive commercial pig farm. Using a stochastic, discrete-time
      metapopulation model, we explored the effect of varying both the probability of
      persistent carriage and that of acquiring MRSA due to contact with pigs on the
      transmission dynamics of MRSA ST398 in humans. In particular, we assessed the
      value and key determinants of the basic reproduction ratio (R(0)) for MRSA ST398.
      Simulations showed that the presence of recurrent exposures with pigs in risky
      populations allows MRSA ST398 to persist in the metapopulation and transmission
      events to occur beyond the farming community, even when the probability of
      persistent carriage is low. We further showed that persistent carriage should
      occur in less than 10% of the time for MRSA ST398 to conserve epidemiological
      characteristics similar to what has been previously reported. These results
      indicate that implementing control policy that only targets human carriers may
      not be sufficient to control MRSA ST398 in the community if it remains in pigs.
      We argue that farm-level control measures should be implemented if an eradication
      programme is to be considered.

PMID- 23112818
TI  - SSU ribosomal DNA-based monitoring of nematode assemblages reveals distinct
      seasonal fluctuations within evolutionary heterogeneous feeding guilds.
AB  - Soils are among the most complex, diverse and competitive habitats on Earth and
      soil biota are responsible for ecosystem services such as nutrient cycling,
      carbon sequestration and remediation of freshwater. The extreme biodiversity
      prohibits the making of a full inventory of soil life. Hence, an appropriate
      indicator group should be selected to determine the biological condition of soil
      systems. Due to their ubiquity and the diverse responses to abiotic and biotic
      changes, nematodes are suitable indicators for environmental monitoring. However,
      the time-consuming microscopic analysis of nematode communities has limited the
      scale at which this indicator group is used. In an attempt to circumvent this
      problem, a quantitative PCR-based tool for the detection of a consistent part of
      the soil nematofauna was developed based on a phylum-wide molecular framework
      consisting of 2,400 full-length SSU rDNA sequences. Taxon-specific primers were
      designed and tested for specificity. Furthermore, relationships were determined
      between the quantitative PCR output and numbers of target nematodes. As a first
      field test for this DNA sequence signature-based approach, seasonal fluctuations
      of nematode assemblages under open canopy (one field) and closed canopy (one
      forest) were monitored. Fifteen taxa from four feeding guilds (covering ~ 65% of
      the free-living nematode biodiversity at higher taxonomical level) were detected
      at two trophic levels. These four feeding guilds are composed of taxa that
      developed independently by parallel evolution and we detected ecologically
      interpretable patterns for free-living nematodes belonging to the lower trophic
      level of soil food webs. Our results show temporal fluctuations, which can be
      even opposite within taxa belonging to the same guild. This research on nematode
      assemblages revealed ecological information about the soil food web that had been
      partly overlooked.

PMID- 23112819
TI  - Inhibiting delta-6 desaturase activity suppresses tumor growth in mice.
AB  - Recent studies have shown that a tumor-supportive microenvironment is
      characterized by high levels of pro-inflammatory and pro-angiogenic eicosanoids
      derived from omega-6 (n-6) arachidonic acid (AA). Although the metabolic pathways
      (COX, LOX, and P450) that generate these n-6 AA eicosanoids have been targeted,
      the role of endogenous AA production in tumorigenesis remains unexplored. Delta-6
      desaturase (D6D) is the rate-limiting enzyme responsible for the synthesis of n-6
      AA and increased D6D activity can lead to enhanced n-6 AA production. Here, we
      show that D6D activity is upregulated during melanoma and lung tumor growth and
      that suppressing D6D activity, either by RNAi knockdown or a specific D6D
      inhibitor, dramatically reduces tumor growth. Accordingly, the content of AA and
      AA-derived tumor-promoting metabolites is significantly decreased. Angiogenesis
      and inflammatory status are also reduced. These results identify D6D as a key
      factor for tumor growth and as a potential target for cancer therapy and
      prevention.

PMID- 23112820
TI  - Differential performance and parasitism of caterpillars on maize inbred lines
      with distinctly different herbivore-induced volatile emissions.
AB  - Plant volatiles induced by insect feeding are known to attract natural enemies of
      the herbivores. Six maize inbred lines that showed distinctly different patterns
      of volatile emission in laboratory assays were planted in randomized plots in the
      Central Mexican Highlands to test their ability to recruit parasitic wasps under
      field conditions. The plants were artificially infested with neonate larvae of
      the fall armyworm Spodoptera frugiperda, and two of its main endoparasitoids,
      Campoletis sonorensis and Cotesia marginiventris, were released in the plots.
      Volatiles were collected from equally treated reference plants in the
      neighbourhood of the experimental field. The cumulative amount of 36 quantified
      volatile compounds determined for each line was in good accordance with findings
      from the laboratory; there was an almost 15-fold difference in total emission
      between the two extreme lines. We found significant differences among the lines
      with respect to the numbers of armyworms recovered from the plants, their average
      weight gain and parasitism rates. Average weight of the caterpillars was
      negatively correlated with the average total amount of volatiles released by the
      six inbred lines. However, neither total volatile emission nor any specific
      single compound within the blend could explain the differential parasitism rates
      among the lines, with the possible exception of (E)-2-hexenal for Campoletis
      sonorensis and methyl salicylate for Cotesia marginiventris. Herbivore-induced
      plant volatiles and/or correlates thereof contribute to reducing insect damage of
      maize plants through direct plant defence and enhanced attraction of parasitoids,
      alleged indirect defence. The potential to exploit these volatiles for pest
      control deserves to be further evaluated.

PMID- 23112821
TI  - Genetic variation in TLR genes in Ugandan and South African populations and
      comparison with HapMap data.
AB  - Genetic epidemiological studies of complex diseases often rely on data from the
      International HapMap Consortium for identification of single nucleotide
      polymorphisms (SNPs), particularly those that tag haplotypes. However, little is
      known about the relevance of the African populations used to collect HapMap data
      for study populations conducted elsewhere in Africa. Toll-like receptor (TLR)
      genes play a key role in susceptibility to various infectious diseases, including
      tuberculosis. We conducted full-exon sequencing in samples obtained from Uganda
      (n = 48) and South Africa (n = 48), in four genes in the TLR pathway: TLR2, TLR4,
      TLR6, and TIRAP. We identified one novel TIRAP SNP (with minor allele frequency
      [MAF] 3.2%) and a novel TLR6 SNP (MAF 8%) in the Ugandan population, and a TLR6
      SNP that is unique to the South African population (MAF 14%). These SNPs were
      also not present in the 1000 Genomes data. Genotype and haplotype frequencies and
      linkage disequilibrium patterns in Uganda and South Africa were similar to
      African populations in the HapMap datasets. Multidimensional scaling analysis of
      polymorphisms in all four genes suggested broad overlap of all of the examined
      African populations. Based on these data, we propose that there is enough
      similarity among African populations represented in the HapMap database to
      justify initial SNP selection for genetic epidemiological studies in Uganda and
      South Africa. We also discovered three novel polymorphisms that appear to be
      population-specific and would only be detected by sequencing efforts.

PMID- 23112822
TI  - Clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"): the
      influence of gender and genetics (CYP2D6, COMT, 5-HTT).
AB  - The synthetic psychostimulant MDMA (+/- 3,4-methylenedioxymethamphetamine,
      ecstasy) acts as an indirect serotonin, dopamine, and norepinephrine agonist and
      as a mechanism-based inhibitor of the cytochrome P-450 2D6 (CYP2D6). It has been
      suggested that women are more sensitive to MDMA effects than men but no clinical
      experimental studies have satisfactorily evaluated the factors contributing to
      such observations. There are no studies evaluating the influence of genetic
      polymorphism on the pharmacokinetics (CYP2D6; catechol-O-methyltransferase, COMT)
      and pharmacological effects of MDMA (serotonin transporter, 5-HTT; COMT). This
      clinical study was designed to evaluate the pharmacokinetics and physiological
      and subjective effects of MDMA considering gender and the genetic polymorphisms
      of CYP2D6, COMT, and 5-HTT. A total of 27 (12 women) healthy, recreational users
      of ecstasy were included (all extensive metabolizers for CYP2D6). A single oral
      weight-adjusted dose of MDMA was administered (1.4 mg/kg, range 75-100 mg) which
      was similar to recreational doses. None of the women were taking oral
      contraceptives and the experimental session was performed during the early
      follicular phase of their menstrual cycle. Principal findings show that subjects
      reached similar MDMA plasma concentrations, and experienced similar positive
      effects, irrespective of gender or CYP2D6 (not taking into consideration poor or
      ultra-rapid metabolizers) or COMT genotypes. However, HMMA plasma concentrations
      were linked to CYP2D6 genotype (higher with two functional alleles). Female
      subjects displayed more intense physiological (heart rate, and oral temperature)
      and negative effects (dizziness, sedation, depression, and psychotic symptoms).
      Genotypes of COMT val158met or 5-HTTLPR with high functionality (val/val or l/*)
      determined greater cardiovascular effects, and with low functionality (met/* or
      s/s) negative subjective effects (dizziness, anxiety, sedation). In conclusion,
      the contribution of MDMA pharmacokinetics following 1.4 mg/kg MDMA to the gender
      differences observed in drug effects appears to be negligible or even null. In
      contrast, 5-HTTLPR and COMT val158met genotypes play a major role. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01447472.

PMID- 23112823
TI  - Perceived parental rejection mediates the influence of serotonin transporter gene
      (5-HTTLPR) polymorphisms on impulsivity in Japanese adults.
AB  - This study examined (1) the interrelationships among 5-HTTLPR genotype, perceived
      parental rejection, and impulsivity, and (2) meditational models in which
      perceived paternal/maternal rejection mediates the relationship between the 5
      HTTLPR genotype and impulsive behaviour. Participants included 403 adults (152
      males and 252 females, mean age = 24.20) who provided genetic data and a set of
      the questionnaires (BIS11; Barratt Impulsiveness Scale-11 and EMBU; Egna Minnen
      av Batraffande Uppfostran). Using SEM (Structural Equation Modeling), we
      evaluated 3 models for both direct and indirect relationships between 5-HTTLPR
      (5HTT) and Impulsivity (IMP), via maternal/fraternal rejection (MAT/FAT). In
      model 1, the direct path from 5HTT and IMP was not significant across the
      mother's and father's analysis. Models 2 and 3 assessed the indirect influence of
      5HTT on IMP through MOT/FAT. The paths of models 2 and 3 were all significant and
      showed a good fit between the hypothesized model and data. Furthermore, the
      effects of the 5-HTTLPR genotype on impulsiveness in this Japanese sample were
      particularly accounted for by perceived rejection from the mother or father. The
      effects from the parents appeared to be robust especially among males. These
      results may help elucidate the specific pathways of risk in relation to genetic
      and environment influences on impulsive phenotypes.

PMID- 23112824
TI  - Favorable changes in lipid profile: the effects of fasting after Ramadan.
AB  - AIMS: We assessed the effect of fasting during Ramadan on blood pressure (BP),
      body weight, plasma lipid, and lipoprotein variables among healthy normal
      individuals. METHODS: 102 (68% male) multi-ethnic volunteers; mean age +/- SD
      (38.7 +/- 10.5 years) were randomly recruited in Al-Ain, United Arab Emirates
      (UAE), to be investigated before Ramadan, one day after the end of Ramadan, and
      four weeks after Ramadan. Anthropometric, demographic, fasting plasma total
      cholesterol (TC), triglyceride (TG), and high density lipoprotein-cholesterol
      (HDL-C) were measured by standard methods, and Low density lipoprotein
      cholesterol (LDL-C) was calculated using Friedewald's formula. RESULTS: 65
      subjects completed the study. We found significant and beneficial changes in
      systolic blood pressure (SBP), body weight, waist circumference (WC), TG, HDL-C
      and LDL-C, at the end of Ramadan, but not in TC. Further, there was a progressive
      and significant increase and decrease in HDL-C and LDL-C levels, respectively,
      four weeks after Ramadan. CONCLUSIONS: We observed significant improvements in
      HDL-C, and LDL-C levels even after four weeks post Ramadan. Ramadan-like fasting
      may be considered for more effective lipid and lipoprotein control.

PMID- 23112825
TI  - Bisphosphonates and risk of upper gastrointestinal cancer--a case control study
      using the General Practice Research Database (GPRD).
AB  - BACKGROUND: Concerns have been raised as to the safety of bisphosphonates; in
      particular a possible link between bisphosphonate use and upper gastrointestinal
      (GI) cancer. Two published studies using different study populations but drawn
      from earlier versions of the same national UK database, reached differing
      conclusions: one finding no evidence for an increase in the risk of gastric or
      oesophageal cancer in bisphosphonate users and one finding a small but
      significantly increased risk of oesophageal cancer linked to duration of
      bisphosphonate use. METHODOLOGY/ PRINCIPAL FINDINGS: Design-A case control study
      comparing bisphosphonate prescribing in cases of upper GI cancer from 1995 to
      2007 using UK primary care electronic health records (GPRD). Main Outcome Measure
      Relative Risk (approximated to Odds Ratio for rare events) for oesophageal and
      gastric cancer development in bisphosphonate users compared to non-users. The
      odds of being a case of oesophageal cancer, adjusted for smoking status, were
      significantly increased in women who had had one or more bisphosphonate
      prescriptions, odds ratio 1.54 (95% CI 1.27-1.88) compared to non-users. There
      was no significant effect on gastric cancer in women, odds ratio adjusted for
      smoking status, 1.06 (95% CI 0.83-1.37) and also no apparent risk in men for
      either oesophageal or gastric cancer, odds ratio adjusted for smoking status 0.78
      (95%CI 0.56-1.09) and 0.87 (95% CI 0.55-1.36) respectively. CONCLUSIONS/
      SIGNIFICANCE: Our results support a small but significant increased risk of
      oesophageal cancer in women prescribed bisphosphonates and is based on the
      largest number of exposed cases to date in the UK.

PMID- 23112826
TI  - The temporal lobes differentiate between the voices of famous and unknown people:
      an event-related fMRI study on speaker recognition.
AB  - It is widely accepted that the perception of human voices is supported by neural
      structures located along the superior temporal sulci. However, there is an
      ongoing discussion to what extent the activations found in fMRI studies are
      evoked by the vocal features themselves or are the result of phonetic processing.
      To show that the temporal lobes are indeed engaged in voice processing, short
      utterances spoken by famous and unknown people were presented to healthy young
      participants whose task it was to identify the familiar speakers. In two event
      related fMRI experiments, the temporal lobes were found to differentiate between
      familiar and unfamiliar voices such that named voices elicited higher BOLD signal
      intensities than unfamiliar voices. Yet, the temporal cortices did not only
      discriminate between familiar and unfamiliar voices. Experiment 2, which required
      overtly spoken responses and allowed to distinguish between four familiarity
      grades, revealed that there was a fine-grained differentiation between all of
      these familiarity levels with higher familiarity being associated with larger
      BOLD signal amplitudes. Finally, we observed a gradual response change such that
      the BOLD signal differences between unfamiliar and highly familiar voices
      increased with the distance of an area from the transverse temporal gyri,
      especially towards the anterior temporal cortex and the middle temporal gyri.
      Therefore, the results suggest that (the anterior and non-superior portions of)
      the temporal lobes participate in voice-specific processing independent from
      phonetic components also involved in spoken speech material.

PMID- 23112827
TI  - Survival prediction based on compound covariate under Cox proportional hazard
      models.
AB  - Survival prediction from a large number of covariates is a current focus of
      statistical and medical research. In this paper, we study a methodology known as
      the compound covariate prediction performed under univariate Cox proportional
      hazard models. We demonstrate via simulations and real data analysis that the
      compound covariate method generally competes well with ridge regression and Lasso
      methods, both already well-studied methods for predicting survival outcomes with
      a large number of covariates. Furthermore, we develop a refinement of the
      compound covariate method by incorporating likelihood information from
      multivariate Cox models. The new proposal is an adaptive method that borrows
      information contained in both the univariate and multivariate Cox regression
      estimators. We show that the new proposal has a theoretical justification from a
      statistical large sample theory and is naturally interpreted as a shrinkage-type
      estimator, a popular class of estimators in statistical literature. Two datasets,
      the primary biliary cirrhosis of the liver data and the non-small-cell lung
      cancer data, are used for illustration. The proposed method is implemented in R
      package "compound.Cox" available in CRAN at http://cran.r-project.org/.

PMID- 23112828
TI  - Identification of a CO2 responsive regulon in Bordetella.
AB  - Sensing the environment allows pathogenic bacteria to coordinately regulate gene
      expression to maximize survival within or outside of a host. Here we show that
      Bordetella species regulate virulence factor expression in response to carbon
      dioxide levels that mimic in vivo conditions within the respiratory tract. We
      found strains of Bordetella bronchiseptica that did not produce adenylate cyclase
      toxin (ACT) when grown in liquid or solid media with ambient air aeration, but
      produced ACT and additional antigens when grown in air supplemented to 5% CO(2).
      Transcriptome analysis and quantitative real time-PCR analysis revealed that
      strain 761, as well as strain RB50, increased transcription of genes encoding
      ACT, filamentous hemagglutinin (FHA), pertactin, fimbriae and the type III
      secretion system in 5% CO(2) conditions, relative to ambient air. Furthermore,
      transcription of cyaA and fhaB in response to 5% CO(2) was increased even in the
      absence of BvgS. In vitro analysis also revealed increases in cytotoxicity and
      adherence when strains were grown in 5% CO(2). The human pathogens B. pertussis
      and B. parapertussis also increased transcription of several virulence factors
      when grown in 5% CO(2), indicating that this response is conserved among the
      classical bordetellae. Together, our data indicate that Bordetella species can
      sense and respond to physiologically relevant changes in CO(2) concentrations by
      regulating virulence factors important for colonization, persistence and evasion
      of the host immune response.

PMID- 23112829
TI  - Upregulation of the Tim-3/galectin-9 pathway of T cell exhaustion in chronic
      hepatitis B virus infection.
AB  - The S-type lectin galectin-9 binds to the negative regulatory molecule Tim-3 on T
      cells and induces their apoptotic deletion or functional inactivation. We
      investigated whether galectin-9/Tim-3 interactions contribute to the deletion and
      exhaustion of the antiviral T cell response in chronic hepatitis B virus
      infection (CHB). We found Tim-3 to be expressed on a higher percentage of CD4 and
      CD8 T cells from patients with CHB than healthy controls (p<0.0001) and to be
      enriched on activated T cells and those infiltrating the HBV-infected liver.
      Direct ex vivo examination of virus-specific CD8 T cells binding HLA-A2/peptide
      multimers revealed that Tim-3 was more highly upregulated on HBV-specific CD8 T
      cells than CMV-specific CD8 T cells or the global CD8 T cell population in
      patients with CHB (p<0.001) or than on HBV-specific CD8 after resolution of
      infection. T cells expressing Tim-3 had an impaired ability to produce IFN-gamma
      and TNF-alpha upon recognition of HBV-peptides and were susceptible to galectin-9
      triggered cell death in vitro. Galectin-9 was detectable at increased
      concentrations in the sera of patients with active CHB-related liver inflammation
      (p = 0.02) and was strongly expressed by Kupffer cells within the liver
      sinusoidal network. Tim-3 blockade resulted in enhanced expansion of HBV-specific
      CD8 T cells able to produce cytokines and mediate cytotoxicity in vitro. Blocking
      PD-1 in combination with Tim-3 enhanced the number of patients from whom
      functional antiviral responses could be recovered and/or the strength of
      responses, indicating that these co-inhibitory molecules play a non-redundant
      role in driving T cell exhaustion in CHB. Patients taking antivirals able to
      potently suppress HBV viraemia continued to express Tim-3 on their T cells and
      respond to Tim-3 blockade. In summary, both Tim-3 and galectin-9 are increased in
      CHB and may contribute to the inhibition and deletion of T cells as they
      infiltrate the HBV-infected liver.

PMID- 23112830
TI  - CD2 promotes human natural killer cell membrane nanotube formation.
AB  - Membrane nanotubes are thin membranous projections that physically connect two
      cells. While nanotubes have been studied in human natural killer (NK) cells and
      are implicated in aiding NK cell cytotoxic function, requirements for their
      formation to susceptible target cells remain incompletely understood. Here we
      demonstrate that the CD2-CD58/48 receptor-ligand interaction promotes and is
      required for nanotube formation in human NK cells. In the CD2(-) NK cell line
      YTS, a stable CD2 expression variant enabled effective nanotube formation, and
      was associated with better cytotoxic function. Importantly, only interactions
      between an NK cell and a susceptible target cell were associated with multiple
      nanotubes and the number of nanotubes was inversely correlated with their length.
      Quantitative live cell fluorescence microscopy of CD2 nanotubes revealed time
      dependent enrichment and localization of CD2 to the nanotube tip, and blocking
      CD2 receptor-ligand interactions prevented nanotube formation. Increased nanotube
      formation was not simply a feature of receptor-ligand pairing, as a KIR-MHC
      interaction in the same cell line system failed to promote nanotube formation.
      Additionally, blocking LFA-1-ICAM and 2B4-CD48 receptor-ligand interactions
      failed to inhibit nanotube formation. Thus only specific receptor-ligand pairs
      promote nanotubes. CD2 also promoted nanotube formation in ex vivo NK cells
      suggesting that CD2 plays a crucial role in the generation of nanotubes between
      an NK cell and its target.

PMID- 23112832
TI  - Present spatial diversity patterns of Theobroma cacao L. in the neotropics
      reflect genetic differentiation in pleistocene refugia followed by human
      influenced dispersal.
AB  - Cacao (Theobroma cacao L.) is indigenous to the Amazon basin, but is generally
      believed to have been domesticated in Mesoamerica for the production of chocolate
      beverage. However, cacao's distribution of genetic diversity in South America is
      also likely to reflect pre-Columbian human influences that were superimposed on
      natural processes of genetic differentiation. Here we present the results of a
      spatial analysis of the intra-specific diversity of cacao in Latin America,
      drawing on a dataset of 939 cacao trees genotypically characterized by means of
      96 SSR markers. To assess continental diversity patterns we performed grid-based
      calculations of allelic richness, Shannon diversity and Nei gene diversity, and
      distinguished different spatially coherent genetic groups by means of cluster
      analysis. The highest levels of genetic diversity were observed in the Upper
      Amazon areas from southern Peru to the Ecuadorian Amazon and the border areas
      between Colombia, Peru and Brazil. On the assumption that the last glaciation
      (22,000-13,000 BP) had the greatest pre-human impact on the current distribution
      and diversity of cacao, we modeled the species' Pleistocene niche suitability and
      overlaid this with present-day diversity maps. The results suggest that cacao was
      already widely distributed in the Western Amazon before the onset of glaciation.
      During glaciations, cacao populations were likely to have been restricted to
      several refugia where they probably underwent genetic differentiation, resulting
      in a number of genetic clusters which are representative for, or closest related
      to, the original wild cacao populations. The analyses also suggested that genetic
      differentiation and geographical distribution of a number of other clusters seem
      to have been significantly affected by processes of human management and
      accompanying genetic bottlenecks. We discuss the implications of these results
      for future germplasm collection and in situ, on farm and ex situ conservation of
      cacao.

PMID- 23112831
TI  - The metagenome-derived enzymes LipS and LipT increase the diversity of known
      lipases.
AB  - Triacylglycerol lipases (EC 3.1.1.3) catalyze both hydrolysis and synthesis
      reactions with a broad spectrum of substrates rendering them especially suitable
      for many biotechnological applications. Most lipases used today originate from
      mesophilic organisms and are susceptible to thermal denaturation whereas only few
      possess high thermotolerance. Here, we report on the identification and
      characterization of two novel thermostable bacterial lipases identified by
      functional metagenomic screenings. Metagenomic libraries were constructed from
      enrichment cultures maintained at 65 to 75  degrees C and screened resulting in
      the identification of initially 10 clones with lipolytic activities.
      Subsequently, two ORFs were identified encoding lipases, LipS and LipT.
      Comparative sequence analyses suggested that both enzymes are members of novel
      lipase families. LipS is a 30.2 kDa protein and revealed a half-life of 48 h at
      70  degrees C. The lipT gene encoded for a multimeric enzyme with a half-life of
      3 h at 70  degrees C. LipS had an optimum temperature at 70  degrees C and LipT
      at 75  degrees C. Both enzymes catalyzed hydrolysis of long-chain (C(12) and
      C(14)) fatty acid esters and additionally hydrolyzed a number of industry
      relevant substrates. LipS was highly specific for (R)-ibuprofen-phenyl ester with
      an enantiomeric excess (ee) of 99%. Furthermore, LipS was able to synthesize 1
      propyl laurate and 1-tetradecyl myristate at 70  degrees C with rates similar to
      those of the lipase CalB from Candida antarctica. LipS represents the first
      example of a thermostable metagenome-derived lipase with significant synthesis
      activities. Its X-ray structure was solved with a resolution of 1.99 A revealing
      an unusually compact lid structure.

PMID- 23112833
TI  - Human V6: functional characterisation and localisation.
AB  - Human visual area V6, in the parieto-occipital sulcus, is thought to have an
      important role in the extraction of optic flow for the monitoring and guidance of
      self-motion (egomotion) because it responds differentially to egomotion
      compatible optic flow when compared to: (a) coherent but egomotion-incompatible
      flow (Cardin & Smith, 2010), and (b) incoherent motion (Pitzalis et al., 2010).
      It is not clear, however, whether V6 responds more strongly to egomotion
      incompatible global motion than to incoherent motion. This is relevant not only
      for determining the functional properties of V6, but also in order to choose
      optimal stimuli for localising V6 accurately with fMRI. Localisation with
      retinotopic mapping is difficult and there is a need for a simple, reliable
      method. We conducted an event-related 3T fMRI experiment in which participants
      viewed a display of dots which either: a) followed a time-varying optic flow
      trajectory in a single, egomotion-compatible (EC) display; b) formed an egomotion
      incompatible (EI) 3 * 3 array of optic flow patches; or c) moved randomly (RM).
      Results from V6 show an ordering of response magnitudes: EC > EI > RM.
      Neighbouring areas V3A and V7 responded more strongly to EC than to RM, but about
      equally to EC and EI. Our results suggest that although V6 may have a general
      role in the extraction of global motion, in clear contrast to neighbouring motion
      areas it is especially concerned with encoding EC stimuli. They suggest two
      strategies for localising V6: (1) contrasting EC and EI; or (2) contrasting EC
      and RM, which is more sensitive but carries a risk of including voxels from
      neighbouring regions that also show a EC > RM preference.

PMID- 23112834
TI  - Comprehensive analysis of common serum liver enzymes as prospective predictors of
      hepatocellular carcinoma in HBV patients.
AB  - BACKGROUND: Serum liver enzymes are frequently tested in clinics to aid disease
      diagnosis. Large observational studies indicated that these enzymes might predict
      cancer risk and mortality. However, no prospective study has reported on their
      relationships with the risk of HBV-related hepatocellular carcinoma (HCC).
      METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the predictive values of four
      routinely tested liver enzymes (alanine aminotransferase [ALT], aspartate
      aminotransferase [AST], alkaline phosphatase [ALP], and gamma-glutamyltransferase
      [GGT]) in HCC risk in a prospectively enrolled clinical cohort of 588 Korean
      American HBV patients. For all four enzymes, the baseline level as well as the
      average and maximum levels during the first 1 or 2 years of follow-up were
      analyzed using multivariate Cox proportional hazards model. Patients were
      categorized into a normal or an elevated group based on the clinical cut-off of
      each enzyme. During a median follow-up of 7.5 years, 52 patients (incidence rate,
      8.8%) developed HCC. The incidence rates were higher in the elevated groups for
      all four enzymes. The most significant finding was for GGT, with the highest
      incidence rate of 16.4% in the elevated group compared to 4.6% in the normal
      group (P<0.001). Compared to patients with normal baseline GGT, those with
      elevated GGT exhibited a significantly increased HCC risk with a hazards ratio
      (HR) of 2.60 (95% confidence interval [CI], 1.41-4.77, P = 0.002). Further
      analyses revealed a cumulative effect between baseline GGT and ALP (HR = 3.41,
      95% CI 1.54-7.56, P = 0.003). CONCLUSIONS SIGNIFICANCE: Serum GGT might predict
      HCC risk in HBV patients individually or jointly with other enzymes.

PMID- 23112835
TI  - Gaps in border controls are related to quarantine alien insect invasions in
      Europe.
AB  - Alien insects are increasingly being dispersed around the world through
      international trade, causing a multitude of negative environmental impacts and
      billions of dollars in economic losses annually. Border controls form the last
      line of defense against invasions, whereby inspectors aim to intercept and stop
      consignments that are contaminated with harmful alien insects. In Europe, member
      states depend on one another to prevent insect introductions by operating a first
      point of entry rule--controlling goods only when they initially enter the
      continent. However, ensuring consistency between border control points is
      difficult because there exists no optimal inspection strategy. For the first
      time, we developed a method to quantify the volume of agricultural trade that
      should be inspected for quarantine insects at border control points in Europe,
      based on global agricultural trade of over 100 million distinct origin-commodity
      species-destination pathways. This metric was then used to evaluate the
      performance of existing border controls, as measured by border interception
      results in Europe between 2003 and 2007. Alarmingly, we found significant gaps
      between the trade pathways that should be inspected and actual number of
      interceptions. Moreover, many of the most likely introduction pathways yielded
      none or very few insect interceptions, because regular interceptions are only
      made on only a narrow range of pathways. European countries with gaps in border
      controls have been invaded by higher numbers of quarantine alien insect species,
      indicating the importance of proper inspections to prevent insect invasions.
      Equipped with an optimal inspection strategy based on the underlying risks of
      trade, authorities globally will be able to implement more effective and
      consistent border controls.

PMID- 23112836
TI  - Aging and weight-ratio perception.
AB  - Past research has provided evidence that older adults have more difficulty than
      younger adults in discriminating small differences in lifted weight (i.e., the
      difference threshold for older adults is higher than that of younger adults).
      Given this result, one might expect that older adults would demonstrate similar
      impairments in weight ratio perception (a suprathreshold judgment) compared to
      younger adults. The current experiment compared the abilities of younger and
      older adults to perceive weight ratios. On any given trial, participants lifted
      two objects in succession and were asked to provide an estimate of the objects'
      weight ratio (the weight of the heavier object relative to the lighter). The
      results showed that while the older participants' weight ratio estimates were as
      reliable as those of the younger participants, they were significantly less
      accurate: the older participants frequently perceived the weight ratios to be
      much higher than they actually were.

PMID- 23112837
TI  - MicroRNA-200 family modulation in distinct breast cancer phenotypes.
AB  - The epithelial to mesenchymal transition (EMT) contributes to tumor invasion and
      metastasis in a variety of cancer types. In human breast cancer, gene expression
      studies have determined that basal-B/claudin-low and metaplastic cancers exhibit
      EMT-related characteristics, but the molecular mechanisms underlying this
      observation are unknown. As the family of miR-200 microRNAs has been shown to
      regulate EMT in normal tissues and cancer, here we evaluated whether the
      expression of the miR-200 family (miR-200f) and their epigenetic state correlate
      with EMT features in human breast carcinomas. We analyzed by qRT-PCR the
      expression of miR-200f members and various EMT-transcriptional inducers in a
      series of 70 breast cancers comprising an array of phenotypic subtypes: estrogen
      receptor positive (ER+), HER2 positive (HER2+), and triple negative (TN),
      including a subset of metaplastic breast carcinomas (MBCs) with sarcomatous
      (homologous or heterologous) differentiation. No MBCs with squamous
      differentiation were included. The DNA methylation status of miR-200f loci in
      tumor samples were inspected using Sequenom MassArray(r) MALDI-TOF platform. We
      also used two non-tumorigenic breast basal cell lines that spontaneously undergo
      EMT to study the modulation of miR-200f expression during EMT in vitro. We
      demonstrate that miR-200f is strongly decreased in MBCs compared with other
      cancer types. TN and HER2+ breast cancers also exhibited lower miR-200f
      expression than ER+ tumors. Significantly, the decreased miR-200f expression
      found in MBCs is accompanied by an increase in the expression levels of EMT
      transcriptional inducers, and hypermethylation of the miR-200c-141 locus. Similar
      to tumor samples, we demonstrated that downregulation of miR-200f and
      hypermethylation of the miR-200c-141 locus, together with upregulation of EMT
      transcriptional inducers also occur in an in vitro cellular model of spontaneous
      EMT. Thus, the expression and methylation status of miR-200f could be used as
      hypothetical biomarkers to assess the occurrence of EMT in breast cancer.

PMID- 23112838
TI  - Double-stranded RNA-dependent protein kinase regulates the motility of breast
      cancer cells.
AB  - Double-stranded RNA (dsRNA)-dependent protein kinase (PKR) is an interferon
      induced protein kinase that plays a central role in the anti-viral process. Due
      to its pro-apoptotic and anti-proliferative action, there is an increased
      interest in PKR modulation as an anti-tumor strategy. PKR is overexpressed in
      breast cancer cells; however, the role of PKR in breast cancer cells is unclear.
      The expression/activity of PKR appears inversely related to the aggressiveness of
      breast cancer cells. The current study investigated the role of PKR in the
      motility/migration of breast cancer cells. The activation of PKR by a synthesized
      dsRNA (PIC) significantly decreased the motility of several breast cancer cell
      lines (BT474, MDA-MB231 and SKBR3). PIC inhibited cell migration and blocked cell
      membrane ruffling without affecting cell viability. PIC also induced the
      reorganization of the actin cytoskeleton and impaired the formation of
      lamellipodia. These effects of PIC were reversed by the pretreatment of a
      selective PKR inhibitor. PIC also activated p38 mitogen-activated protein kinase
      (MAPK) and its downstream MAPK-activated protein kinase 2 (MK2). PIC-induced
      activation of p38 MAPK and MK2 was attenuated by the PKR inhibitor and the PKR
      siRNA, but a selective p38 MAPK inhibitor (SB203580) or other MAPK inhibitors did
      not affect PKR activity, indicating that PKR is upstream of p38 MAPK/MK2. Cofilin
      is an actin severing protein and regulates membrane ruffling, lamellipodia
      formation and cell migration. PIC inhibited cofilin activity by enhancing its
      phosphorylation at Ser3. PIC activated LIM kinase 1 (LIMK1), an upstream kinase
      of cofilin in a p38 MAPK-dependent manner. We concluded that the activation of
      PKR suppressed cell motility by regulating the p38 MAPK/MK2/LIMK/cofilin pathway.

PMID- 23112839
TI  - Carnitine deficiency in OCTN2-/- newborn mice leads to a severe gut and immune
      phenotype with widespread atrophy, apoptosis and a pro-inflammatory response.
AB  - We have investigated the gross, microscopic and molecular effects of carnitine
      deficiency in the neonatal gut using a mouse model with a loss-of-function
      mutation in the OCTN2 (SLC22A5) carnitine transporter. The tissue carnitine
      content of neonatal homozygous (OCTN2(-/-)) mouse small intestine was markedly
      reduced; the intestine displayed signs of stunted villous growth, early signs of
      inflammation, lymphocytic and macrophage infiltration and villous structure
      breakdown. Mitochondrial beta-oxidation was active throughout the GI tract in
      wild type newborn mice as seen by expression of 6 key enzymes involved in beta
      oxidation of fatty acids and genes for these 6 enzymes were up-regulated in
      OCTN2(-/-) mice. There was increased apoptosis in gut samples from OCTN2(-/-)
      mice. OCTN2(-/-) mice developed a severe immune phenotype, where the thymus,
      spleen and lymph nodes became atrophied secondary to increased apoptosis.
      Carnitine deficiency led to increased expression of CD45-B220(+) lymphocytes with
      increased production of basal and anti-CD3-stimulated pro-inflammatory cytokines
      in immune cells. Real-time PCR array analysis in OCTN2(-/-) mouse gut epithelium
      demonstrated down-regulation of TGF-beta/BMP pathway genes. We conclude that
      carnitine plays a major role in neonatal OCTN2(-/-) mouse gut development and
      differentiation, and that severe carnitine deficiency leads to increased
      apoptosis of enterocytes, villous atrophy, inflammation and gut injury.

PMID- 23112840
TI  - Identification, expression and activity analyses of five novel duck beta
      defensins.
AB  - In the current study, five novel avian beta-defensins (AvBDs) were identified and
      characterized in tissues from Peking ducks (Anas platyrhynchos). The nucleotide
      sequences of these cDNAs comprised 198 bp, 182 bp, 201 bp, 204 bp, and 168 bp,
      and encoded 65, 60, 66, 67, and 55 amino acids, respectively. Homology,
      characterization and comparison of these genes with AvBD from other avian species
      confirmed that they were Apl_AvBD1, 3, 5, 6, and 16. Recombinant AvBDs were
      produced and purified by expressing these genes in Escherichia coli. In addition,
      peptides were synthesized according to the respective AvBD sequences.
      Investigation of the antibacterial activity of the Apl_AvBDs showed that all of
      them exhibited antibacterial activity against all 12 bacteria investigated
      (P<0.05 or P<0.01). In addition, the antibacterial activity of all of the AvBDs
      against M. tetragenus and P. multocida decreased significantly in the presence of
      150 mM NaCl (P<0.01). None of the AvBDs showed hemolytic activity. Consistent
      with their broad-spectrum antibacterial activity, the five novel Apl_AvBDs
      inhibited replication of duck hepatitis virus (DHV) in vitro significantly
      (P<0.05). The mRNA expression of all five Apl_AvBD in most tissues, including
      immune organs and the liver, was upregulated in response to DHV infection at
      different time points. These findings provide evidence that these defensins
      activate the immune response to combat microbial infection.

PMID- 23112841
TI  - Population coding of forelimb joint kinematics by peripheral afferents in
      monkeys.
AB  - Various peripheral receptors provide information concerning position and movement
      to the central nervous system to achieve complex and dexterous movements of
      forelimbs in primates. The response properties of single afferent receptors to
      movements at a single joint have been examined in detail, but the population
      coding of peripheral afferents remains poorly defined. In this study, we obtained
      multichannel recordings from dorsal root ganglion (DRG) neurons in cervical
      segments of monkeys. We applied the sparse linear regression (SLiR) algorithm to
      the recordings, which selects useful input signals to reconstruct movement
      kinematics. Multichannel recordings of peripheral afferents were performed by
      inserting multi-electrode arrays into the DRGs of lower cervical segments in two
      anesthetized monkeys. A total of 112 and 92 units were responsive to the passive
      joint movements or the skin stimulation with a painting brush in Monkey 1 and
      Monkey 2, respectively. Using the SLiR algorithm, we reconstructed the temporal
      changes of joint angle, angular velocity, and acceleration at the elbow, wrist,
      and finger joints from temporal firing patterns of the DRG neurons. By
      automatically selecting a subset of recorded units, the SLiR achieved superior
      generalization performance compared with a regularized linear regression
      algorithm. The SLiR selected not only putative muscle units that were responsive
      to only the passive movements, but also a number of putative cutaneous units
      responsive to the skin stimulation. These results suggested that an ensemble of
      peripheral primary afferents that contains both putative muscle and cutaneous
      units encode forelimb joint kinematics of non-human primates.

PMID- 23112843
TI  - Maternal androgens increase sibling aggression, dominance, and competitive
      ability in the siblicidal black-legged kittiwake (Rissa tridactyla).
AB  - Animals and plants routinely produce more offspring than they can afford to rear.
      Mothers can favour certain young by conferring on them competitive advantages
      such as a leading position in the birth sequence, more resources or hormones.
      Avian mothers create hatching asynchrony within a clutch and at the same time
      bestow the eggs with different concentrations of androgens that may enhance or
      counteract the competitive advantage experienced by early-hatching "core" young.
      In siblicidal birds, core young assume a dominant social position in the nest due
      to their size advantage and when threatened with starvation fatally attack
      subdominant later-hatching "marginal" young. A role for maternal androgens in
      siblicidal aggression has frequently been suggested but never tested. We studied
      this in the facultatively siblicidal black-headed kittiwake. We found that
      marginal eggs contain higher instead of lower concentrations of androgens than
      core eggs. Surprisingly, exposure to experimentally elevated yolk androgens
      increased sibling aggression and dominance, even though in nature marginal eggs
      never produce dominant chicks. We propose the "adoption facilitation hypothesis"
      to explain this paradox. This cliff-nesting colonial species has a high adoption
      rate: ejected marginal kittiwake chicks frequently fall into other nests
      containing chicks of similar or smaller size and exposure to yolk androgens might
      help them integrate themselves into a foster nest.

PMID- 23112842
TI  - The apolipoprotein E (APOE) gene appears functionally monomorphic in chimpanzees
      (Pan troglodytes).
AB  - BACKGROUND: The human apolipoprotein E (APOE) gene is polymorphic, with three
      primary alleles (E2, E3, E4) that differ at two key non-synonymous sites. These
      alleles are functionally different in how they bind to lipoproteins, and this
      genetic variation is associated with phenotypic variation for several medical
      traits, including cholesterol levels, cardiovascular health, Alzheimer's disease
      risk, and longevity. The relative frequencies of these alleles vary across human
      populations, and the evolution and maintenance of this diversity is much debated.
      Previous studies comparing human and chimpanzee APOE sequences found that the
      chimpanzee sequence is most similar to the human E4 allele, although the
      resulting chimpanzee protein might function like the protein coded for by the
      human E3 allele. However, these studies have used sequence data from a single
      chimpanzee and do not consider whether chimpanzees, like humans, show intra
      specific and subspecific variation at this locus. METHODOLOGY AND PRINCIPAL
      FINDINGS: To examine potential intraspecific variation, we sequenced the APOE
      gene of 32 chimpanzees. This sample included 20 captive individuals representing
      the western subspecies (P. troglodytes verus) and 12 wild individuals
      representing the eastern subspecies (P. t. schweinfurthii). Variation in our
      resulting sequences was limited to one non-coding, intronic SNP, which showed
      fixed differences between the two subspecies. We also compared APOE sequences for
      all available ape genera and fossil hominins. The bonobo APOE protein is
      identical to that of the chimpanzee, and the Denisovan APOE exhibits all four
      human-specific, non-synonymous changes and appears functionally similar to the
      human E4 allele. CONCLUSIONS: We found no coding variation within and between
      chimpanzee populations, suggesting that the maintenance of functionally diverse
      APOE polymorphisms is a unique feature of human evolution.

PMID- 23112844
TI  - Neonatal thyroid-stimulating hormone concentrations in Belgium: a useful
      indicator for detecting mild iodine deficiency?
AB  - It has been proposed that neonatal thyroid-stimulating hormone (TSH)
      concentrations are a good indicator of iodine deficiency in the population. A
      frequency of neonatal TSH concentrations above 5 mU/L below 3% has been proposed
      as the threshold indicating iodine sufficiency. The objective of the present
      study was to evaluate feasibility and usefulness of nation-wide neonatal TSH
      concentration screening results to assess iodine status in Belgium. All newborns
      born in Belgium during the period 2009-2011 (n = 377713) were included in the
      study, except those suffering from congenital hypothyroidism and premature
      neonates. The frequency of neonatal TSH concentrations above 5 mU/L from 2009 to
      2011 in Belgium fluctuated between 2.6 and 3.3% in the centres using the same TSH
      assay. There was a significant inverse association between neonatal TSH level and
      birth weight. The longer the duration between birth and screening, the lower the
      TSH level. Neonatal TSH levels were significantly lower in winter than in spring
      or autumn and significantly lower in spring and summer than in autumn while
      significantly higher in spring compared to summer. In conclusion, despite that
      pregnant women in Belgium are mildly iodine deficient, the frequency of neonatal
      TSH concentrations above 5 mU/L was very low, suggesting that the neonatal TSH
      threshold proposed for detecting iodine deficiency needs to be re-evaluated.
      Although neonatal TSH is useful to detect severe iodine deficiency, it should not
      be recommended presently for the evaluation of iodine status in mildly iodine
      deficient regions.

PMID- 23112846
TI  - Electrophysiology of single and aggregate Cx43 hemichannels.
AB  - Connexin43 (Cx43) is the most ubiquitous gap junction protein in the human body
      and is essential for cell-to-cell communication in a variety of organs and organ
      systems. As a result, Cx43 is responsible for mediating both electrical and
      chemical signals, passing dissolved solutes and small signaling molecules between
      cells in a coordinated fashion. Here, we explore the electrophysiological
      properties of hemichannels formed from Cx43 and Cx43 fused to eGFP (Cx43eGFP) and
      their interactions in a planar lipid membrane (BLM). Unlike in vivo patch clamp
      experiments, Cx43 was purified and isolated from other membrane constituents
      allowing elucidation of individual protein responses to various electrical and
      chemical stimuli. Using this system, we examined hemichannel electrophysiology
      and the roles of several well-known gap junction blockers, namely: lanthanum,
      heptanol, carbenoxalone and lindane. We also observed a critical number of
      hemichannels required for an accelerated conductance increase, an emergent
      electrical signature indicative of plaque formation.

PMID- 23112845
TI  - Epistasis analysis for estrogen metabolic and signaling pathway genes on young
      ischemic stroke patients.
AB  - BACKGROUND: Endogenous estrogens play an important role in the overall
      cardiocirculatory system. However, there are no studies exploring the hormone
      metabolism and signaling pathway genes together on ischemic stroke, including
      sulfotransferase family 1E (SULT1E1), catechol-O-methyl-transferase (COMT), and
      estrogen receptor alpha (ESR1). METHODS: A case-control study was conducted on
      305 young ischemic stroke subjects aged </= 50 years and 309 age-matched healthy
      controls. SULT1E1 -64G/A, COMT Val158Met, ESR1 c.454-397 T/C and c.454-351 A/G
      genes were genotyped and compared between cases and controls to identify single
      nucleotide polymorphisms associated with ischemic stroke susceptibility. Gene
      gene interaction effects were analyzed using entropy-based multifactor
      dimensionality reduction (MDR), classification and regression tree (CART), and
      traditional multiple regression models. RESULTS: COMT Val158Met polymorphism
      showed a significant association with susceptibility of young ischemic stroke
      among females. There was a two-way interaction between SULT1E1 -64G/A and COMT
      Val158Met in both MDR and CART analysis. The logistic regression model also
      showed there was a significant interaction effect between SULT1E1 -64G/A and COMT
      Val158Met on ischemic stroke of the young (P for interaction = 0.0171). We
      further found that lower estradiol level could increase the risk of young
      ischemic stroke for those who carry either SULT1E1 or COMT risk genotypes,
      showing a significant interaction effect (P for interaction = 0.0174).
      CONCLUSIONS: Our findings support that a significant epistasis effect exists
      among estrogen metabolic and signaling pathway genes and gene-environment
      interactions on young ischemic stroke subjects.

PMID- 23112847
TI  - Similar cerebral motor plans for real and virtual actions.
AB  - A simple movement, such as pressing a button, can acquire different meanings by
      producing different consequences, such as starting an elevator or switching a TV
      channel. We evaluated whether the brain activity preceding a simple action is
      modulated by the expected consequences of the action itself. To further this aim,
      the motor-related cortical potentials were compared during two key-press actions
      that were identical from the kinematics point of view but different in both
      meaning and consequences. In one case (virtual grasp), the key-press started a
      video clip showing a hand moving toward a cup and grasping it; in the other case,
      the key-press did not produce any consequence (key-press). A third condition
      (real grasp) was also compared, in which subjects actually grasped the cup,
      producing the same action presented in the video clip. Data were collected from
      fifteen subjects. The results showed that motor preparation for virtual grasp
      (starting 3 s before the movement onset) was different from that of the key-press
      and similar to the real grasp preparation-as if subjects had to grasp the cup in
      person. In particular, both virtual and real grasp presented a posterior parietal
      negativity preceding activity in motor and pre-motor areas. In summary, this
      finding supports the hypothesis that motor preparation is affected by the meaning
      of the action, even when the action is only virtual.

PMID- 23112848
TI  - Regulatory roles of cytokinins and cytokinin signaling in response to potassium
      deficiency in Arabidopsis.
AB  - Potassium (K) is an important plant macronutrient that has various functions
      throughout the whole plant over its entire life span. Cytokinins (CKs) are known
      to regulate macronutrient homeostasis by controlling the expression of nitrate,
      phosphate and sulfate transporters. Although several studies have described how
      CKs signal deficiencies for some macronutrients, the roles of CKs in K signaling
      are poorly understood. CK content has been shown to decrease under K-starved
      conditions. Specifically, a CK-deficient mutant was more tolerant to low K than
      wild-type; however, a plant with an overaccumulation of CKs was more sensitive to
      low K. These results suggest that K deprivation alters CK metabolism, leading to
      a decrease in CK content. To investigate this phenomenon further, several
      Arabidopsis lines, including a CK-deficient mutant and CK receptor mutants, were
      analyzed in low K conditions using molecular, genetic and biochemical approaches.
      ROS accumulation and root hair growth in low K were also influenced by CKs. CK
      receptor mutants lost the responsiveness to K-deficient signaling, including ROS
      accumulation and root hair growth, but the CK-deficient mutant accumulated more
      ROS and exhibited up-regulated expression of HAK5, which is a high-affinity K
      uptake transporter gene that is rapidly induced by low K stress in ROS- and
      ethylene-dependent manner in response to low K. From these results, we conclude
      that a reduction in CK levels subsequently allows fast and effective stimulation
      of low K-induced ROS accumulation, root hair growth and HAK5 expression, leading
      to plant adaptation to low K conditions.

PMID- 23112849
TI  - Attitudes toward infection prophylaxis in pediatric oncology: a qualitative
      approach.
AB  - BACKGROUND: The risks and benefits of infection prophylaxis are uncertain in
      children with cancer and thus, preferences should be considered in decision
      making. The purpose of this report was to describe the attitudes of parents,
      children and healthcare professionals to infection prophylaxis in pediatric
      oncology. METHODS: THE STUDY WAS COMPLETED IN THREE PHASES: 1) An initial
      qualitative pilot to identify the main attributes influencing the decision to use
      infection prophylaxis, which were then incorporated into a discrete choice
      experiment; 2) A think aloud during the discrete choice experiment in which
      preferences for infection prophylaxis were elicited quantitatively; and 3) In
      depth follow up interviews. Interviews were recorded verbatim and analyzed using
      an iterative, thematic analysis. Final themes were selected using a consensus
      approach. RESULTS: A total of 35 parents, 22 children and 28 healthcare
      professionals participated. All three groups suggested that the most important
      factor influencing their decision making was the effect of prophylaxis on
      reducing the chance of death. Themes of importance to the three groups included
      antimicrobial resistance, side effects of medications, the financial impact of
      outpatient prophylaxis and the route and schedule of administration. CONCLUSION:
      Effect of prophylaxis on risk of death was a key factor in decision making. Other
      identified factors were antimicrobial resistance, side effects of medication,
      financial impact and administration details. Better understanding of factors
      driving decision making for infection prophylaxis will help facilitate future
      implementation of prophylactic regiments.

PMID- 23112850
TI  - Population differences in brain morphology and microstructure among Chinese,
      Malay, and Indian neonates.
AB  - We studied a sample of 75 Chinese, 73 Malay, and 29 Indian healthy neonates
      taking part in a cohort study to examine potential differences in neonatal brain
      morphology and white matter microstructure as a function of ethnicity using both
      structural T2-weighted magnetic resonance imaging (MRI) and diffusion tensor
      imaging (DTI). We first examined the differences in global size and morphology of
      the brain among the three groups. We then constructed the T2-weighted MRI and DTI
      atlases and employed voxel-based analysis to investigate ethnic differences in
      morphological shape of the brain from the T2-weighted MRI, and white matter
      microstructure measured by fractional anisotropy derived from DTI. Compared with
      Malay neonates, the brains of Indian neonates' tended to be more elongated in
      anterior and posterior axis relative to the superior-inferior axis of the brain
      even though the total brain volume was similar among the three groups. Although
      most anatomical regions of the brain were similar among Chinese, Malay, and
      Indian neonates, there were anatomical variations in the spinal-cerebellar and
      cortical-striatal-thalamic neural circuits among the three populations. The
      population-related brain regions highlighted in our study are key anatomical
      substrates associated with sensorimotor functions.

PMID- 23112851
TI  - Surface morphology of amygdala is associated with trait anxiety.
AB  - Previous neuroimaging studies have suggested a role of amygdala in trait anxiety
      level, in which amygdala was typically treated as a whole. To date, it remains
      unknown whether the morphology of specific subregions of amygdala are associated
      with trait anxiety. Here, we employed a shape analysis approach to locate the
      association between its morphology and trait anxiety on the surface of amygdala.
      24 healthy young participants were included. The boundary of amygdala for each
      subject was first manually outlined using high-resolution magnetic resonance (MR)
      image, followed by 3D surface reconstruction and parameterization using spherical
      harmonic description. Two point-wise metrics, direct displacement between the
      individual surface and atlas surface and its normal projection, were used to
      quantify the surface morphology of amygdala. Statistical analysis revealed
      significant correlations between the two surface metrics and trait anxiety
      levels, which were located around the lateral and central nucleus of right
      amygdala. Our results provided localized information for the association between
      amygdala and trait anxiety, and suggested a central role of the lateral and
      central nucleus of right amygdala on trait anxiety.

PMID- 23112852
TI  - SIV genome-wide pyrosequencing provides a comprehensive and unbiased view of
      variation within and outside CD8 T lymphocyte epitopes.
AB  - Deep sequencing technology is revolutionizing our understanding of HIV/SIV
      evolution. It is known that acute SIV sequence variation within CD8 T lymphocyte
      (CD8-TL) epitopes is similar among MHC-identical animals, but we do not know
      whether this persists into the chronic phase. We now determine whether chronic
      viral variation in MHC-identical animals infected with clonal SIV is similar
      throughout the entire coding sequence when using a sensitive deep sequencing
      approach. We pyrosequenced the entire coding sequence of the SIV genome isolated
      from a unique cohort of four SIVmac239-infected, MHC-identical Mauritian
      cynomolgus macaques (MCM) 48 weeks after infection; one MCM in the cohort became
      an elite controller. Among the three non-controllers, we found that genome-wide
      sequences were similar between animals and we detected increased sequence
      complexity within 64% of CD8-TL epitopes when compared to Sanger sequencing
      methods. When we compared sequences between the MHC-matched controller and the
      three non-controllers, we found the viral population in the controller was less
      diverse and accumulated different variants than the viral populations in the non
      controllers. Importantly, we found that initial PCR amplification of viral cDNA
      did not significantly affect the sequences detected, suggesting that data
      obtained by pyrosequencing PCR-amplified viral cDNA accurately represents the
      diversity of sequences replicating within an animal. This demonstrates that
      chronic sequence diversity across the entire SIV coding sequence is similar among
      MHC-identical animals with comparable viral loads when infected with the same
      clonal virus stock. Additionally, our approach to genome-wide SIV sequencing
      accurately reflects the diversity of sequences present in the replicating viral
      population. In sum, our study suggests that genome-wide pyrosequencing of
      immunodeficiency viruses captures a thorough and unbiased picture of sequence
      diversity, and may be a useful approach to employ when evaluating which sequences
      to include as part of a vaccine immunogen.

PMID- 23112853
TI  - Soluble ST2 associates with diabetes but not established cardiovascular risk
      factors: a new inflammatory pathway of relevance to diabetes?
AB  - Preliminary data mostly from animal models suggest the sST2/IL-33 pathway may
      have causal relevance for vascular disease and diabetes and thus point to a
      potential novel inflammatory link to cardiometabolic disease. However, the
      characterisation of sST2 levels in terms of metabolic or vascular risk in man is
      completely lacking. We sought to address this gap via a comprehensive analysis of
      risk factor and vascular correlates of sST2 in a cross-sectional study (pSoBid).
      We measured sST2 in plasma in 639 subjects and comprehensively related it to
      cardiovascular and diabetes risk factors and imaged atherosclerosis measures.
      Circulating sST2 levels increased with age, were lower in women and in highest
      earners. After adjusting for age and gender, sST2 levels associated strongly with
      markers of diabetes, including triglycerides [effect estimate (EE) per 1 standard
      deviation increase in sST2:1.05 [95%CI 1.01,1.10]), liver function (alanine
      aminotransaminase [ALT] and gamma-glutamyl transferase [GGT]: EE 1.05 [1.01,1.09]
      and 1.13 [1.07,1.19] respectively), glucose (1.02 [1.00,1.03]) and sICAM-1 (1.05
      [1.02,1.07]). However, sST2 levels were not related to smoking, cholesterol,
      blood pressure, or atheroma (carotid intima media thickness, plaque presence).
      These results suggest that sST2 levels, in individuals largely without vascular
      disease, are related principally to markers associated with diabetes and ectopic
      fat and add support for a role of sST2 in diabetes. Further mechanistic studies
      determining how sST2 is linked to diabetes pathways may offer new insights into
      the inflammatory paradigm for type 2 diabetes.

PMID- 23112854
TI  - Metabolic profiling reveals sphingosine-1-phosphate kinase 2 and lyase as key
      targets of (phyto-) estrogen action in the breast cancer cell line MCF-7 and not
      in MCF-12A.
AB  - To search for new targets of anticancer therapies using phytoestrogens we
      performed comparative metabolic profiling of the breast cancer cell line MCF-7
      and the non-tumorigenic breast cell line MCF-12A. Application of gas
      chromatography-mass spectrometry (GC-MS) revealed significant differences in the
      metabolic levels after exposure with 17beta-estradiol, genistein or a composition
      of phytoestrogens within a native root flax extract. We observed the metabolites
      3-(4-hydroxyphenyl)-lactic acid, cis-aconitic acid, 11-beta-hydroxy-progesterone,
      chenodeoxycholic acid and triacontanoic acid with elevated levels due to estrogen
      action. Particularly highlighted were metabolites of the sphingolipid metabolism.
      Sphingosine and its dihydro derivate as well as ethanolaminephosphate were
      significantly altered after exposure with 1 nM 17beta-estradiol in the cell line
      MCF-7, while MCF-12A was not affected. Treatment with genistein and the flax
      extract normalized the sphingosine concentrations to the basic levels found in
      MCF-12A cells. We could further demonstrate that the expression levels of the
      sphingosine metabolizing enzymes: sphingosine-1-phosphate kinase (Sphk) and lyase
      (S1P lyase) were significantly influenced by estrogens as well as phytoestrogens.
      The isoform Sphk2 was overexpressed in the tumorigenic cell line MCF-7, while S1P
      lyase was predominantly expressed in the non-tumorigenic cell line MCF-12A.
      Importantly, in MCF-7 the weak S1P lyase expression could be significantly
      increased after exposure with 10 uM genistein and 1 ug/ml root flax extract.
      Here, we present, for the first time, an analysis of metabolic response of
      phytoestrogens to breast cancer cell lines. The contrasting regulation of
      sphingolipid enzymes in MCF-7 and MCF-12A render them as preferred targets for
      future anticancer strategies.

PMID- 23112855
TI  - Comparative mitochondrial genomics within and among yeast species of the
      Lachancea genus.
AB  - Yeasts are leading model organisms for mitochondrial genome studies. The
      explosion of complete sequence of yeast mitochondrial (mt) genomes revealed a
      wide diversity of organization and structure between species. Recently, genome
      wide polymorphism survey on the mt genome of isolates of a single species,
      Lachancea kluyveri, was also performed. To compare the mitochondrial genome
      evolution at two hierarchical levels: within and among closely related species,
      we focused on five species of the Lachancea genus, which are close relatives of
      L. kluyveri. Hence, we sequenced the complete mt genome of L. dasiensis, L.
      nothofagi, L. mirantina, L. fantastica and L. meyersii. The phylogeny of the
      Lachancea genus was explored using these data. Analysis of intra- and
      interspecific variability across the whole Lachancea genus led to the same
      conclusions regarding the mitochondrial genome evolution. These genomes exhibit a
      similar architecture and are completely syntenic. Nevertheless, genome sizes vary
      considerably because of the variations of the intergenic regions and the intron
      content, contributing to mitochondrial genome plasticity. The high variability of
      the intergenic regions stands in contrast to the high level of similarity of
      protein sequences. Quantification of the selective constraints clearly revealed
      that most of the mitochondrial genes are under purifying selection in the whole
      genus.

PMID- 23112856
TI  - Spatial and temporal organization of chromosome duplication and segregation in
      the cyanobacterium Synechococcus elongatus PCC 7942.
AB  - The spatial and temporal control of chromosome duplication and segregation is
      crucial for proper cell division. While this process is well studied in
      eukaryotic and some prokaryotic organisms, relatively little is known about it in
      prokaryotic polyploids such as Synechococcus elongatus PCC 7942, which is known
      to possess one to eight copies of its single chromosome. Using a fluorescent
      repressor-operator system, S. elongatus chromosomes and chromosome replication
      forks were tagged and visualized. We found that chromosomal duplication is
      asynchronous and that the total number of chromosomes is correlated with cell
      length. Thus, replication is independent of cell cycle and coupled to cell
      growth. Replication events occur in a spatially random fashion. However, once
      assembled, replisomes move in a constrained manner. On the other hand, we found
      that segregation displays a striking spatial organization in some cells.
      Chromosomes transiently align along the major axis of the cell and timing of
      alignment was correlated to cell division. This mechanism likely contributes to
      the non-random segregation of chromosome copies to daughter cells.

PMID- 23112857
TI  - MeCP2 dependent heterochromatin reorganization during neural differentiation of a
      novel Mecp2-deficient embryonic stem cell reporter line.
AB  - The X-linked Mecp2 is a known interpreter of epigenetic information and mutated
      in Rett syndrome, a complex neurological disease. MeCP2 recruits HDAC complexes
      to chromatin thereby modulating gene expression and, importantly regulates higher
      order heterochromatin structure. To address the effects of MeCP2 deficiency on
      heterochromatin organization during neural differentiation, we developed a
      versatile model for stem cell in vitro differentiation. Therefore, we modified
      murine Mecp2 deficient (Mecp2(-/y)) embryonic stem cells to generate cells
      exhibiting green fluorescent protein expression upon neural differentiation.
      Subsequently, we quantitatively analyzed heterochromatin organization during
      neural differentiation in wild type and in Mecp2 deficient cells. We found that
      MeCP2 protein levels increase significantly during neural differentiation and
      accumulate at constitutive heterochromatin. Statistical analysis of Mecp2 wild
      type neurons revealed a significant clustering of heterochromatin per nuclei with
      progressing differentiation. In contrast we found Mecp2 deficient neurons and
      astroglia cells to be significantly impaired in heterochromatin reorganization.
      Our results (i) introduce a new and manageable cellular model to study the
      molecular effects of Mecp2 deficiency, and (ii) support the view of MeCP2 as a
      central protein in heterochromatin architecture in maturating cells, possibly
      involved in stabilizing their differentiated state.

PMID- 23112858
TI  - Natural changes in brain temperature underlie variations in song tempo during a
      mating behavior.
AB  - The song of a male zebra finch is a stereotyped motor sequence whose tempo varies
      with social context--whether or not the song is directed at a female bird--as
      well as with the time of day. The neural mechanisms underlying these changes in
      tempo are unknown. Here we show that brain temperature recorded in freely
      behaving male finches exhibits a global increase in response to the presentation
      of a female bird. This increase strongly correlates with, and largely explains,
      the faster tempo of songs directed at a female compared to songs produced in
      social isolation. Furthermore, we find that the observed diurnal variations in
      song tempo are also explained by natural variations in brain temperature. Our
      findings suggest that brain temperature is an important variable that can
      influence the dynamics of activity in neural circuits, as well as the temporal
      features of behaviors that some of these circuits generate.

PMID- 23112859
TI  - Abscisic acid signaling: thermal stability shift assays as tool to analyze
      hormone perception and signal transduction.
AB  - Abscisic acid (ABA) is a plant hormone that plays important roles in growth and
      development. ABA is also the central regulator to protect plants against abiotic
      stresses, such as drought, high salinity, and adverse temperatures, and ABA
      signaling is therefore a promising biotechnological target for the generation of
      crops with increased stress resistance. Recently, a core signal transduction
      pathway has been established, in which ABA receptors, type 2C protein
      phosphatases, and AMPK-related protein kinases control the regulation of
      transcription factors, ion channels, and enzymes. Here we use a simple protein
      thermal stability shift assay to independently validate key aspects of this
      pathway and to demonstrate the usefulness of this technique to detect and
      characterize very weak (Kd >= 50 uM) interactions between receptors and
      physiological and synthetic agonists, to determine and analyze protein-protein
      interactions, and to screen small molecule inhibitors.

PMID- 23112861
TI  - How archer fish achieve a powerful impact: hydrodynamic instability of a pulsed
      jet in Toxotes jaculatrix.
AB  - Archer fish knock down insects anchored to vegetation by hitting them with a
      precisely aimed jet of water. The striking force of the jet at the impact is such
      to overcome the strong anchoring forces of insects. The origin of the
      effectiveness of such hunting mechanism has been long searched for inside of the
      fish, in the unsuccessful attempt to identify internal structures dedicated to
      the amplification of muscular power. Here we perform a kinematic analysis of the
      jet emitted by two specimens of Toxotes jaculatrix. We estimate that at the
      impact the jet conveys a typical specific power of about 3000 W/kg, which is well
      above the maximum specific power of the order of 500 W/kg deliverable by a
      vertebrate muscle. Unexpectedly, we find that the amplification of muscular power
      occurs outside of the fish, and is due to a hydrodynamic instability of the jet
      akin to those occurring in Drop-on-Demand inkjet printing. The investigated fish
      are found to modulate the velocity of the jet at the orifice to favor the
      formation of a single, large, water drop that hits the prey abruptly with a large
      momentum. The observed mechanism represents a remarkable example of use of an
      external hydrodynamic lever that does possibly not entail the high evolutionary
      cost needed for the development of highly specialized internal structures
      dedicated to the storing of mechanical energy.

PMID- 23112860
TI  - Sp1 transcription factor and GATA1 cis-acting elements modulate testis-specific
      expression of mouse cyclin A1.
AB  - Cyclin A1 is a male germ cell-specific cell cycle regulator that is essential for
      spermatogenesis. It is unique among the cyclins by virtue of its highly
      restricted expression in vivo, being present in pachytene and diplotene
      spermatocytes and not in earlier or later stages of spermatogenesis. To begin to
      understand the molecular mechanisms responsible for this narrow window of
      expression of the mouse cyclin A1 (Ccna1) gene, we carried out a detailed
      analysis of its promoter. We defined a 170-bp region within the promoter and
      showed that it is involved in repression of Ccna1 in cultured cells. Within this
      region we identified known cis-acting transcription factor binding sequences,
      including an Sp1-binding site and two GATA1-binding sites. Neither Sp1 nor GATA1
      is expressed in pachytene spermatocytes and later stages of germ cell
      differentiation. Sp1 is readily detected at earlier stages of spermatogenesis.
      Site-directed mutagenesis demonstrated that neither factor alone was sufficient
      to significantly repress expression driven by the Ccna1 promoter, while
      concurrent binding of Sp1, and most likely GATA1 and possibly additional factors
      was inhibitory. Occupancy of Sp1 on the Ccna1 promoter and influence of GATA1
      dependent cis-acting elements was confirmed by ChIP analysis in cell lines and
      most importantly, in spermatogonia. In contrast with many other testis-specific
      genes, the CpG island methylation status of the Ccna1 promoter was similar among
      various tissues examined, irrespective of whether Ccna1 was transcriptionally
      active, suggesting that this regulatory mechanism is not involved in the
      restricted expression of Ccna1.

PMID- 23112862
TI  - The Genetic and Environmental Foundation of the Simple View of Reading in
      Chinese.
AB  - The Simple View of Reading (SVR) in Chinese was examined in a genetically
      sensitive design. A total of 270 pairs of Chinese twins (190 pairs of monozygotic
      twins and 80 pairs of same-sex dizygotic twins) were tested on Chinese vocabulary
      and word reading at the mean age 7.8 years and reading comprehension of sentences
      and passages one year later. Results of behavior-genetic analyses showed that
      both vocabulary and word reading had significant independent genetic influences
      on reading comprehension, and the two factors together accounted for most but not
      all of the genetic influences on reading comprehension. In addition, sentence
      comprehension had a stronger genetic correlation with word reading while passage
      comprehension showed a trend of stronger genetic overlap with vocabulary. These
      findings suggest that the genetic foundation of the SVR in Chinese is largely
      supported in that language comprehension and decoding are two core skills for
      reading comprehension in nonalphabetic as well as alphabetic written languages.

PMID- 23112863
TI  - Groundwater contaminated with hexavalent chromium [Cr (VI)]: a health survey and
      clinical examination of community inhabitants (Kanpur, India).
AB  - BACKGROUND: We assessed the health effects of hexavalent chromium groundwater
      contamination (from tanneries and chrome sulfate manufacturing) in Kanpur, India.
      METHODS: The health status of residents living in areas with high Cr (VI)
      groundwater contamination (N = 186) were compared to residents with similar
      social and demographic features living in communities having no elevated Cr (VI)
      levels (N = 230). Subjects were recruited at health camps in both the areas.
      Health status was evaluated with health questionnaires, spirometry and blood
      hematology measures. Cr (VI) was measured in groundwater samples by
      diphenylcarbazide reagent method. RESULTS: Residents from communities with known
      Cr (VI) contamination had more self-reports of digestive and dermatological
      disorders and hematological abnormalities. GI distress was reported in 39.2% vs.
      17.2% males (AOR = 3.1) and 39.3% vs. 21% females (AOR = 2.44); skin
      abnormalities in 24.5% vs. 9.2% males (AOR = 3.48) and 25% vs. 4.9% females (AOR
      = 6.57). Residents from affected communities had greater RBCs (among 30.7% males
      and 46.1% females), lower MCVs (among 62.8% males) and less platelets (among 68%
      males and 72% females) than matched controls. There were no differences in
      leucocytes count and spirometry parameters. CONCLUSIONS: Living in communities
      with Cr (VI) groundwater is associated with gastrointestinal and dermatological
      complaints and abnormal hematological function. Limitations of this study include
      small sample size and the lack of long term follow-up.

PMID- 23112864
TI  - One-step Agrobacterium mediated transformation of eight genes essential for
      rhizobium symbiotic signaling using the novel binary vector system pHUGE.
AB  - Advancement in plant research is becoming impaired by the fact that the transfer
      of multiple genes is difficult to achieve. Here we present a new binary vector
      for Agrobacterium tumefaciens mediated transformation, pHUGE-Red, in concert with
      a cloning strategy suited for the transfer of up to nine genes at once. This
      vector enables modular cloning of large DNA fragments by employing Gateway
      technology and contains DsRED1 as visual selection marker. Furthermore, an R/Rs
      inducible recombination system was included allowing subsequent removal of the
      selection markers in the newly generated transgenic plants. We show the
      successful use of pHUGE-Red by transferring eight genes essential for Medicago
      truncatula to establish a symbiosis with rhizobia bacteria as one 74 kb T-DNA
      into four non-leguminous species; strawberry, poplar, tomato and tobacco. We
      provide evidence that all transgenes are expressed in the root tissue of the non
      legumes. Visual control during the transformation process and subsequent marker
      gene removal makes the pHUGE-Red vector an excellent tool for the efficient
      transfer of multiple genes.

PMID- 23112865
TI  - Stability of p53 homologs.
AB  - Most proteins have not evolved for maximal thermal stability. Some are only
      marginally stable, as for example, the DNA-binding domains of p53 and its
      homologs, whose kinetic and thermodynamic stabilities are strongly correlated.
      Here, we applied high-throughput methods using a real-time PCR thermocycler to
      study the stability of several full-length orthologs and paralogs of the p53
      family of transcription factors, which have diverse functions, ranging from
      tumour suppression to control of developmental processes. From isothermal
      denaturation fluorimetry and differential scanning fluorimetry, we found that
      full-length proteins showed the same correlation between kinetic and
      thermodynamic stability as their isolated DNA-binding domains. The stabilities of
      the full-length p53 orthologs were marginal and correlated with the temperature
      of their organism, paralleling the stability of the isolated DNA-binding domains.
      Additionally, the paralogs p63 and p73 were significantly more stable and long
      lived than p53. The short half-life of p53 orthologs and the greater persistence
      of the paralogs may be biologically relevant.

PMID- 23112866
TI  - Epigenetic disruption of the PIWI pathway in human spermatogenic disorders.
AB  - Epigenetic changes are involved in a wide range of common human diseases.
      Although DNA methylation defects are known to be associated with male infertility
      in mice, their impact on human deficiency of sperm production has yet to be
      determined. We have assessed the global genomic DNA methylation profiles in human
      infertile male patients with spermatogenic disorders by using the Infinium Human
      Methylation27 BeadChip. Three populations were studied: conserved
      spermatogenesis, spermatogenic failure due to germ cell maturation defects, and
      Sertoli cell-only syndrome samples. A disease-associated DNA methylation profile,
      characterized by targeting members of the PIWI-associated RNA (piRNA) processing
      machinery, was obtained. Bisulfite genomic sequencing and pyrosequencing in a
      large cohort (n = 46) of samples validated the altered DNA methylation patterns
      observed in piRNA-processing genes. In particular, male infertility was
      associated with the promoter hypermethylation-associated silencing of PIWIL2 and
      TDRD1. The downstream effects mediated by the epigenetic inactivation of the PIWI
      pathway genes were a defective production of piRNAs and a hypomethylation of the
      LINE-1 repetitive sequence in the affected patients. Overall, our data suggest
      that DNA methylation, at least that affecting PIWIL2/TDRD1, has a role in the
      control of gene expression in spermatogenesis and its imbalance contributes to an
      unsuccessful germ cell development that might explain a group of male infertility
      disorders.

PMID- 23112867
TI  - Osteopontin-enhanced hepatic metastasis of colorectal cancer cells.
AB  - Liver metastasis is a major cause of mortality from colorectal cancer (CRC).
      However, mechanisms underlying this process are largely unknown. Osteopontin
      (OPN) is a secreted phosphorylated glycoprotein that is involved in tumor
      migration and metastasis. The role of OPN in cancer is currently unclear. In this
      study, OPN mRNA was examined in tissues from CRC, adjacent normal mucosa, and
      liver metastatic lesions using quantitative real-time PCR analysis. The protein
      expression of OPN and its receptors (integrin alphav and CD44 v6) was detected by
      using an immunohistochemical (IHC) method. The role of OPN in liver metastasis
      was studied in established colon cancer Colo-205 and SW-480 cell lines
      transfected with sense- or antisense-OPN eukaryotic expression plasmids by flow
      cytometry and cell adhesion assay. Fluorescence redistribution after
      photobleaching (FRAP) was used to study gap functional intercellular
      communication (GJIC) among OPN-transfected cells. It was found that OPN was
      highly expressed in metastatic hepatic lesions from CRC compared to primary CRC
      tissue and adjacent normal mucosa. The expression of OPN mRNA in tumor tissues
      was significantly related with the CRC stages. OPN expression was also detected
      in normal hepatocytes surrounding CRC metastatic lesions. Two known receptors of
      OPN, integrin alphav and CD44v6 proteins, were strongly expressed in hepatocytes
      from normal liver. CRC cells with forced OPN expression exhibited increased
      heterotypic adhesion with endothelial cells and weakened intercellular
      communication. OPN plays a significant role in CRC metastasis to liver through
      interaction with its receptors in hepatocytes, decreased homotypic adhesion, and
      enhanced heterotypic adhesion.

PMID- 23112868
TI  - Dissociation between brain amyloid deposition and metabolism in early mild
      cognitive impairment.
AB  - BACKGROUND: The hypothetical model of dynamic biomarkers for Alzheimer's disease
      (AD) describes high amyloid deposition and hypometabolism at the mild cognitive
      impairment (MCI) stage. However, it remains unknown whether brain amyloidosis and
      hypometabolism follow the same trajectories in MCI individuals. We used the
      concept of early MCI (EMCI) and late MCI (LMCI) as defined by the Alzheimer's
      disease Neuroimaging Initiative (ADNI)-Go in order to compare the biomarker
      profile between EMCI and LMCI. OBJECTIVES: To examine the global and voxel-based
      neocortical amyloid burden and metabolism among individuals who are cognitively
      normal (CN), as well as those with EMCI, LMCI and mild AD. METHODS: In the
      present study, 354 participants, including CN (n = 109), EMCI (n = 157), LMCI (n
      = 39) and AD (n = 49), were enrolled between September 2009 and November 2011
      through ADNI-GO and ADNI-2. Brain amyloid load and metabolism were estimated
      using [(18)F]AV45 and [(18)F]fluorodeoxyglucose ([(18)F]FDG) PET, respectively.
      Uptake ratio images of [(18)F]AV45 and [(18)F]FDG were calculated by dividing the
      summed PET image by the median counts of the grey matter of the cerebellum and
      pons, respectively. Group differences of global [(18)F]AV45 and [(18)F]FDG were
      analyzed using ANOVA, while the voxel-based group differences were estimated
      using statistic parametric mapping (SPM). RESULTS: EMCI patients showed higher
      global [(18)F]AV45 retention compared to CN and lower uptake compared to LMCI.
      SPM detected higher [(18)F]AV45 uptake in EMCI compared to CN in the precuneus,
      posterior cingulate, medial and dorsal lateral prefrontal cortices, bilaterally.
      EMCI showed lower [(18)F]AV45 retention than LMCI in the superior temporal,
      inferior parietal, as well as dorsal lateral prefrontal cortices, bilaterally.
      Regarding to the global [(18)F]FDG, EMCI patients showed no significant
      difference from CN and a higher uptake ratio compared to LMCI. At the voxel
      level, EMCI showed higher metabolism in precuneus, hippocampus, entorhinal and
      inferior parietal cortices, as compared to LMCI. CONCLUSIONS: The present results
      indicate that brain metabolism remains normal despite the presence of significant
      amyloid accumulation in EMCI. These results suggest a role for anti-amyloid
      interventions in EMCI aiming to delay or halt the deposition of amyloid and
      related metabolism impairment.

PMID- 23112869
TI  - Parasite burden in hamsters infected with two different strains of leishmania
      (Leishmania) infantum: "Leishman Donovan units" versus real-time PCR.
AB  - To develop and test new therapeutics and immune prophylaxis strategies for
      visceral leishmaniasis (VL), understanding tissue parasitism evolution after
      experimental infection with Leishmania infantum is important. Experimental
      infection in a hamster model (Mesocricetus auratus) reproduces several typical
      aspects of canine and human VL that are closely related to the inoculum's route.
      We quantified the parasitism in the liver and spleen of hamsters experimentally
      infected by various routes (intradermal, intraperitoneal, and intracardiac [IC])
      and different strains of L. infantum (MHOM/BR/74/PP75 and Wild) and compared two
      different methodologies to evaluate tissue parasitism (Leishman Donovan units
      [LDU] and real-time qPCR). In addition, the quantification of specific total-IgG
      in the serum of uninfected and infected hamsters was determined by ELISA. The
      animals were followed for 1, 3, 6 and 9 months post-infection for survival
      analysis. We found that infection with the Wild strain by the IC route resulted
      in higher mortality. Positive antibody (IgG) responses were detected with higher
      peaks at 6 and 9 months in the IC group inoculated with PP75 strain. However, in
      animals infected with the Wild strain the IgG levels were elevated in all
      infected groups during all the time evaluated. We also observed by LDU analysis
      that the IC route lead to higher parasitism in the liver and spleen with both
      strains. Furthermore, qPCR showed higher sensitivity for identifying animals with
      low parasitic burden. In conclusion, qPCR can be useful for assessing parasitism
      in the spleen and liver of a hamster model infected with L. infantum independent
      of the route of infection, and this technique may become an essential tool for
      assessing parasite density in the hamster model after experimental treatment or
      immunization with potential vaccine candidates.

PMID- 23112870
TI  - Phagocytosis and respiratory burst activity in lumpsucker (Cyclopterus lumpus L.)
      leucocytes analysed by flow cytometry.
AB  - In the present study, we have isolated leucocytes from peripheral blood, head
      kidney and spleen from lumpsucker (Cyclopterus lumpus L.), and performed
      functional studies like phagocytosis and respiratory burst, as well as
      morphological and cytochemical analyses. Different leucocytes were identified,
      such as lymphocytes, monocytes/macrophages and polymorphonuclear cells with bean
      shaped or bilobed nuclei. In addition, cells with similar morphology as described
      for dendritic cells in trout were abundant among the isolated leucocytes. Flow
      cytometry was successfully used for measuring phagocytosis and respiratory burst
      activity. The phagocytic capacity and ability were very high, and cells with
      different morphology in all three leucocyte preparations phagocytised beads
      rapidly. Due to lack of available cell markers, the identity of the phagocytic
      cells could not be determined. The potent non-specific phagocytosis was in
      accordance with a high number of cells positive for myeloperoxidase, an enzyme
      involved in oxygen-dependent killing mechanism present in phagocytic cells.
      Further, high respiratory burst activity was present in the leucocytes samples,
      verifying a potent oxygen- dependent degradation. At present, the specific
      antibody immune response could not be measured, as immunoglobulin or B-cells have
      not yet been isolated. Therefore, analyses of the specific immune response in
      this fish species await further clarification. The present study presents the
      first analyses of lumpsucker immunity and also the first within the order
      Scopaeniformes.

PMID- 23112871
TI  - A three-dimensional comparison of tick-borne flavivirus infection in mammalian
      and tick cell lines.
AB  - Tick-borne flaviviruses (TBFV) are sustained in nature through cycling between
      mammalian and tick hosts. In this study, we used African green monkey kidney
      cells (Vero) and Ixodes scapularis tick cells (ISE6) to compare virus-induced
      changes in mammalian and arthropod cells. Using confocal microscopy, transmission
      electron microscopy (TEM), and electron tomography (ET), we examined viral
      protein distribution and the ultrastructural changes that occur during TBFV
      infection. Within host cells, flaviviruses cause complex rearrangement of
      cellular membranes for the purpose of virus replication. Virus infection was
      accompanied by a marked expansion in endoplasmic reticulum (ER) staining and
      markers for TBFV replication were localized mainly to the ER in both cell lines.
      TEM of Vero cells showed membrane-bound vesicles enclosed in a network of
      dilated, anastomosing ER cisternae. Virions were seen within the ER and were
      sometimes in paracrystalline arrays. Tubular structures or elongated vesicles
      were occasionally noted. In acutely and persistently infected ISE6 cells,
      membrane proliferation and vesicles were also noted; however, the extent of
      membrane expansion and the abundance of vesicles were lower and no viral
      particles were observed. Tubular profiles were far more prevalent in persistently
      infected ISE6 cells than in acutely infected cells. By ET, tubular profiles, in
      persistently infected tick cells, had a cross-sectional diameter of 60-100 nm,
      reached up to 800 nm in length, were closed at the ends, and were often arranged
      in fascicle-like bundles, shrouded with ER membrane. Our experiments provide
      analysis of viral protein localization within the context of both mammalian and
      arthropod cell lines as well as both acute and persistent arthropod cell
      infection. Additionally, we show for the first time 3D flavivirus infection in a
      vector cell line and the first ET of persistent flavivirus infection.

PMID- 23112872
TI  - Corticosteroids in the treatment of community-acquired pneumonia in adults: a
      meta-analysis.
AB  - BACKGROUND: The benefit of corticosteroids in community-acquired pneumonia (CAP)
      remains controversial. We did a meta-analysis to include all the randomized
      controlled trials (RCTs) which used corticosteroids as adjunctive therapy, to
      examine the benefits and risks of corticosteroids in the treatment of CAP in
      adults. METHODS: Databases including Pubmed, EMBASE, the Cochrane controlled
      trials register, and Google Scholar were searched to find relevant trials.
      Randomized and quasi-randomized trials of corticosteroids treatment in adult
      patients with CAP were included. Effects on primary outcome (mortality) and
      secondary outcomes (adverse events) were accessed in this meta-analysis. RESULTS:
      Nine trials involving 1001 patients were included. Use of corticosteroids did not
      significantly reduce mortality (Peto odds ratio [OR] 0.62, 95% confidence
      interval [CI] 0.37-1.04; P = 0.07). In the subgroup analysis by the severity, a
      survival benefit was found among severe CAP patients (Peto OR 0.26, 95% CI 0.11
      0.64; P = 0.003). In subgroup analysis by duration of corticosteroids treatment,
      significant reduced mortality was found among patients with prolonged
      corticosteroids treatment (Peto OR 0.51, 95% CI 0.26-0.97; P = 0.04; I(2) = 37%).
      Corticosteroids increased the risk of hyperglycemia (Peto OR 2.64, 95% CI 1.68
      4.15; P<0.0001), but without increasing the risk of gastroduodenal bleeding (Peto
      OR 1.67, 95% CI 0.41-6.80; P = 0.47) and superinfection (Peto OR 1.36, 95% CI
      0.65-2.84; P = 0.41). CONCLUSION: Results from this meta-analysis did not suggest
      a benefit for corticosteroids treatment in patients with CAP. However, the use of
      corticosteroids was associated with improved mortality in severe CAP. In
      addition, prolonged corticosteroids therapy suggested a beneficial effect on
      mortality. These results should be confirmed by future adequately powered
      randomized trials.

PMID- 23112873
TI  - Monitoring of xenograft tumor growth and response to chemotherapy by non-invasive
      in vivo multispectral fluorescence imaging.
AB  - A continuous monitoring of the whole tumor burden of individuals in orthotopic
      tumor models is a desirable aim and requires non-invasive imaging methods. Here
      we investigated whether quantification of a xenograft tumor intrinsic
      fluorescence signal can be used to evaluate tumor growth and response to
      chemotherapy. Stably fluorescence protein (FP) expressing cell clones of
      colorectal carcinoma and germ cell tumor lines were generated by lentiviral
      transduction using the FPs eGFP, dsRed2, TurboFP635, and mPlum. Applying
      subcutaneous tumor models in different experimental designs, specific
      correlations between measured total fluorescence intensity (FI) and the tumor
      volume (V) could be established. The accuracy of correlation of FI and V varied
      depending on the cell model used. The application of deep-red FP expressing
      xenografts (TurboFP635, mPlum) was observed to result in improved correlations.
      This was also reflected by the results of a performed error analysis. In a model
      of visceral growing mPlum tumors, measurements of FI could be used to follow
      growth and response to chemotherapy. However, in some cases final necropsy
      revealed the existence of additional, deeper located tumors that had not been
      detected in vivo by their mPlum signal. Consistently, only the weights of the
      tumors that were detected in vivo based on their mPlum signal correlated with FI.
      In conclusion, as long as tumors are visualized by their fluorescence signal the
      FI can be used to evaluate tumor burden. Deep-red FPs are more suitable for in
      vivo applications as compared to eGFP and dsRed2.

PMID- 23112874
TI  - The AprV5 subtilase is required for the optimal processing of all three
      extracellular serine proteases from Dichelobacter nodosus.
AB  - Dichelobacter nodosus is the principal causative agent of ovine footrot and its
      extracellular proteases are major virulence factors. Virulent isolates of D.
      nodosus secrete three subtilisin-like serine proteases: AprV2, AprV5 and BprV.
      These enzymes are each synthesized as precursor molecules that include a signal
      (pre-) peptide, a pro-peptide and a C-terminal extension, which are processed to
      produce the mature active forms. The function of the C-terminal regions of these
      proteases and the mechanism of protease processing and secretion are unknown.
      AprV5 contributes to most of the protease activity secreted by D. nodosus. To
      understand the role of the C-terminal extension of AprV5, we constructed a series
      of C-terminal-deletion mutants in D. nodosus by allelic exchange. The proteases
      present in the resultant mutants and their complemented derivatives were examined
      by protease zymogram analysis, western blotting and mass spectrometry. The
      results showed that the C-terminal region of AprV5 is required for the normal
      expression of protease activity, deletion of this region led to a delay in the
      processing of these enzymes. D. nodosus is an unusual bacterium in that it
      produces three closely related extracellular serine proteases. We have now shown
      that one of these enzymes, AprV5, is responsible for its own maturation, and for
      the optimal cleavage of AprV2 and BprV, to their mature active forms. These
      studies have increased our understanding of how this important pathogen processes
      these virulence-associated extracellular proteases and secretes them into its
      external environment.

PMID- 23112875
TI  - Uric acid stimulates fructokinase and accelerates fructose metabolism in the
      development of fatty liver.
AB  - Excessive dietary fructose intake may have an important role in the current
      epidemics of fatty liver, obesity and diabetes as its intake parallels the
      development of these syndromes and because it can induce features of metabolic
      syndrome. The effects of fructose to induce fatty liver, hypertriglyceridemia and
      insulin resistance, however, vary dramatically among individuals. The first step
      in fructose metabolism is mediated by fructokinase (KHK), which phosphorylates
      fructose to fructose-1-phosphate; intracellular uric acid is also generated as a
      consequence of the transient ATP depletion that occurs during this reaction. Here
      we show in human hepatocytes that uric acid up-regulates KHK expression thus
      leading to the amplification of the lipogenic effects of fructose. Inhibition of
      uric acid production markedly blocked fructose-induced triglyceride accumulation
      in hepatocytes in vitro and in vivo. The mechanism whereby uric acid stimulates
      KHK expression involves the activation of the transcription factor ChREBP, which,
      in turn, results in the transcriptional activation of KHK by binding to a
      specific sequence within its promoter. Since subjects sensitive to fructose often
      develop phenotypes associated with hyperuricemia, uric acid may be an underlying
      factor in sensitizing hepatocytes to fructose metabolism during the development
      of fatty liver.

PMID- 23112876
TI  - ATF6alpha promotes astroglial activation and neuronal survival in a chronic mouse
      model of Parkinson's disease.
AB  - Accumulating evidence suggests a crucial role for the unfolded protein response
      (UPR) in Parkinson's disease (PD). In this study, we investigated the relevance
      of the UPR in a mouse model of chronic MPTP/probenecid (MPTP/P) injection, which
      causes severe and persistent degeneration of dopaminergic neurons. Enhanced
      activation of the UPR branches, including ATF6alpha and PERK/eIF2alpha/ATF4, was
      observed after MPTP/P injections into mice. Deletion of the ATF6alpha gene
      accelerated neuronal degeneration and ubiquitin accumulation relatively early in
      the MPTP/P injection course. Surprisingly, astroglial activation was strongly
      suppressed, and production of the brain-derived neurotrophic factor (BDNF) and
      anti-oxidative genes, such as heme oxygenase-1 (HO-1) and xCT, in astrocytes were
      reduced in ATF6alpha -/- mice after MPTP/P injections. Decreased BDNF expression
      in ATF6alpha -/- mice was associated with decreased expression of GRP78, an
      ATF6alpha-dependent molecular chaperone in the ER. Decreased HO-1 and xCT levels
      were associated with decreased expression of the ATF4-dependent pro-apoptotic
      gene CHOP. Consistent with these results, administration of the UPR-activating
      reagent tangeretin (5,6,7,8,4'-pentamethoxyflavone; IN19) into mice enhanced the
      expression of UPR-target genes in both dopaminergic neurons and astrocytes, and
      promoted neuronal survival after MPTP/P injections. These results suggest that
      the UPR is activated in a mouse model of chronic MPTP/P injection, and
      contributes to the survival of nigrostriatal dopaminergic neurons, in part,
      through activated astrocytes.

PMID- 23112877
TI  - Transcriptome analysis of the Asian honey bee Apis cerana cerana.
AB  - BACKGROUND: The Eastern hive honey bee, Apis cerana cerana is a native and widely
      bred honey bee species in China. Molecular biology research about this honey bee
      species is scarce, and genomic information for A. c. cerana is not currently
      available. Transcriptome and expression profiling data for this species are
      therefore important resources needed to better understand the biological
      mechanisms of A. c. cerana. In this study, we obtained the transcriptome
      information of A. c. cerana by RNA-sequencing and compared gene expression
      differences between queens and workers of A. c. cerana by digital gene expression
      (DGE) analysis. RESULTS: Using high-throughput Illumina RNA sequencing we
      obtained 51,581,510 clean reads corresponding to 4.64 Gb total nucleotides from a
      single run. These reads were assembled into 46,999 unigenes with a mean length of
      676 bp. Based on a sequence similarity search against the five public databases
      (NR, Swissport, GO, COG, KEGG) with a cut-off E-value of 10(-5) using BLASTX, a
      total of 24,630 unigenes were annotated with gene descriptions, gene ontology
      terms, or metabolic pathways. Using these transcriptome data as references we
      analyzed the gene expression differences between the queens and workers of A. c.
      cerana using a tag-based digital gene expression method. We obtained 5.96 and
      5.66 million clean tags from the queen and worker samples, respectively. A total
      of 414 genes were differentially expressed between them, with 189 up-regulated
      and 225 down-regulated in queens. CONCLUSIONS: Our transcriptome data provide a
      comprehensive sequence resource for future A. c. cerana study, establishing an
      important public information platform for functional genomic studies in A. c.
      cerana. Furthermore, the DGE data provide comprehensive gene expression
      information for the queens and workers, which will facilitate our understanding
      of the molecular mechanisms of the different physiological aspects of the two
      castes.

PMID- 23112878
TI  - Aflatoxin B1 up-regulates insulin receptor substrate 2 and stimulates hepatoma
      cell migration.
AB  - Aflatoxin B1 (AFB1) is a potent carcinogen that can induce hepatocellular
      carcinoma. AFB1-8,9-exo-epoxide, one of AFB1 metabolites, acts as a mutagen to
      react with DNA and induce gene mutations, including the tumor suppressor p53. In
      addition, AFB1 reportedly stimulates IGF receptor activation. Aberrant activation
      of IGF-I receptor (IGF-IR) signaling is tightly associated with various types of
      human tumors. In the current study, we investigated the effects of AFB1 on key
      elements in IGF-IR signaling pathway, and the effects of AFB1 on hepatoma cell
      migration. The results demonstrated that AFB1 induced IGF-IR, Akt, and Erk1/2
      phosphorylation in hepatoma cell lines HepG2 and SMMC-7721, and an immortalized
      human liver cell line Chang liver. AFB1 also down-regulated insulin receptor
      substrate (IRS) 1 but paradoxically up-regulated IRS2 through preventing
      proteasomal degradation. Treatment of hepatoma cells and Chang liver cells with
      IGF-IR inhibitor abrogated AFB1-induced Akt and Erk1/2 phosphorylation. In
      addition, IRS2 knockdown suppressed AFB1-induced Akt and Erk1/2 phosphorylation.
      Finally, AFB1 stimulated hepatoma cell migration. IGF-IR inhibitor or IRS2
      knockdown suppressed AFB1-induced hepatoma cell migration. These data demonstrate
      that AFB1 stimulates hepatoma cell migration through IGF-IR/IRS2 axis.

PMID- 23112879
TI  - Dietary manipulation and social isolation alter disease progression in a murine
      model of coronary heart disease.
AB  - BACKGROUND: Mice with a deficiency in the HDL receptor SR-BI and low expression
      of a modified apolipoprotein E gene (SR-BI KO/ApoeR61(h/h)) called 'HypoE' when
      fed an atherogenic, 'Paigen' diet develop occlusive, atherosclerotic coronary
      arterial disease (CHD), myocardial infarctions (MI), and heart dysfunction and
      die prematurely (50% mortality ~40 days after initiation of this diet). Because
      few murine models share with HypoE mice these cardinal, human-like, features of
      CHD, HypoE mice represent a novel, small animal, diet-inducible and genetically
      tractable model for CHD. To better describe the properties of this model, we have
      explored the effects of varying the composition and timing of administration of
      atherogenic diets, as well as social isolation vs. group housing, on these
      animals. METHODOLOGY/PRINCIPAL FINDINGS: HypoE mice were maintained on a standard
      lab chow diet (control) until two months of age. Subsequently they received one
      of three atherogenic diets (Paigen, Paigen without cholate, Western) or control
      diet for varying times and were housed in groups or singly, and we determined the
      plasma cholesterol levels, extent of cardiomegaly and/or survival. The rate of
      disease progression could be reduced by lowering the severity of the atherogenic
      diet and accelerated by social isolation. Disease could be induced by Paigen
      diets either containing or free of cholate. We also established conditions under
      which CHD could be initiated by an atherogenic diet and then subsequently, by
      replacing this diet with standard lab chow, hypercholesterolemia could be reduced
      and progression to early death prevented. CONCLUSIONS/SIGNIFICANCE: HypoE mice
      provide a powerful, surgery-free, diet-'titratable' small animal model that can
      be used to study the onset of recovery from occlusive, atherosclerotic CHD and
      heart failure due to MI. HypoE mice can be used for the analysis of the effects
      of environment (diet, social isolation) on a variety of features of
      cardiovascular disease.

PMID- 23112881
TI  - The Past and Future of GI Oncology Research.

PMID- 23112880
TI  - The trail less traveled: individual decision-making and its effect on group
      behavior.
AB  - Social insect colonies are complex systems in which the interactions of many
      individuals lead to colony-level collective behaviors such as foraging. However,
      the emergent properties of collective behaviors may not necessarily be adaptive.
      Here, we examine symmetry breaking, an emergent pattern exhibited by some social
      insects that can lead colonies to focus their foraging effort on only one of
      several available food patches. Symmetry breaking has been reported to occur in
      several ant species. However, it is not clear whether it arises as an unavoidable
      epiphenomenon of pheromone recruitment, or whether it is an adaptive behavior
      that can be controlled through modification of the individual behavior of
      workers. In this paper, we used a simulation model to test how symmetry breaking
      is affected by the degree of non-linearity of recruitment, the specific mechanism
      used by individuals to choose between patches, patch size, and forager number.
      The model shows that foraging intensity on different trails becomes increasingly
      asymmetric as the recruitment response of individuals varies from linear to
      highly non-linear, supporting the predictions of previous work. Surprisingly, we
      also found that the direction of the relationship between forager number (i.e.,
      colony size) and asymmetry varied depending on the specific details of the
      decision rule used by individuals. Limiting the size of the resource produced a
      damping effect on asymmetry, but only at high forager numbers. Variation in the
      rule used by individual ants to choose trails is a likely mechanism that could
      cause variation among the foraging behaviors of species, and is a behavior upon
      which selection could act.

PMID- 23112882
TI  - Colorectal cancer in alaska native people, 2005-2009.
AB  - BACKGROUND: Colorectal cancer (CRC) is the most frequently diagnosed cancer among
      Alaska Native (AN) people, and the second leading cause of cancer death. The
      incidence rate for the combined years 1999 through 2003 was 30% higher than the
      rate among U.S. whites (USWs) for the same period. Current incidence rates may
      serve to monitor the impact of screening programs in reducing CRC in the AN
      population. METHODS: Incidence data are from the Alaska Native Tumor Registry and
      the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER)
      Program. We compared AN CRC incidence, survival rates, and stage at diagnosis
      with rates in USWs for cases diagnosed from 2005 through 2009. Relative survival
      calculations were produced in SEER*Stat by the actuarial method. RESULTS: The CRC
      age-adjusted incidence rate among AN men and women combined was higher than those
      in USW men and women (84 vs. 43/100,000; P < .05; AN:USW rate ratio [RR] = 2.0).
      The greatest differences between rates in AN people and USWs were for tumors in
      the hepatic flexure (RR = 3.1) and in the transverse (RR = 2.9) and sigmoid (RR =
      2.5) regions of the colon. Rectal cancer rates among AN people were significantly
      higher than rates in USWs (21 vs.12/100,000). Five-year relative survival
      proportions by stage at diagnosis indicate that the CRC 5-year relative survival
      was similar in AN people and USWs for the period 2004 through 2009. CONCLUSIONS:
      The high rate of CRC in AN people emphasizes the need for screening programs and
      interventions to reduce known modifiable risks. Research in methods to promote
      healthy behaviors among AN people is greatly needed.

PMID- 23112883
TI  - A phase 2 trial of ixabepilone plus cetuximab in first-line treatment of
      metastatic pancreatic cancer.
AB  - BACKGROUND: The aim of this phase 2 study was to evaluate the safety and efficacy
      of ixabepilone plus cetuximab in patients with advanced pancreatic cancer.
      METHODS: Eligible patients had advanced pancreatic adenocarcinoma that was
      metastatic or not amenable to resection, a Karnofsky performance status >=70%,
      and no prior therapy for advanced disease. Patients received ixabepilone 32
      mg/m(2) (3-hour IV infusion) every 3 weeks and cetuximab 250 mg/m(2) (1-hour IV
      infusion) weekly. The primary efficacy end point was the 6-month survival rate.
      Secondary end points included tumor response rate, overall survival, progression
      free survival, and tolerability. RESULTS: A total of 54 patients were enrolled on
      this study. The 6-month survival rate was 57% (31/54: 95% CI: 43-71%) with a
      median overall survival of 7.6 months (95% CI: 5.5-12.2 months). Patients who
      developed acneiform rash (n = 36) had a median survival of 8.8 months, compared
      with 2.6 months for those without rash (n = 18). Of 31 patients with measurable
      disease (defined as response-evaluable), 4 had confirmed partial responses and an
      additional 24 had stable disease. The combination was generally well-tolerated
      with the most common grade 3/4 hematological toxicities being leucopenia (39%)
      and neutropenia (33%). The most common grade 3/4 nonhematologic toxicity was
      fatigue (17%). CONCLUSIONS: The combination of ixabepilone and cetuximab was
      active and had acceptable toxicity. The efficacy results are similar to single
      agent ixabepilone and gemcitabine-based combination therapies in patients with
      advanced pancreatic cancer. Exploratory analyses suggest a trend toward improved
      survival for patients who experienced rash.

PMID- 23112884
TI  - The expanding role of somatostatin analogs in the management of neuroendocrine
      tumors.
AB  - BACKGROUND: Neuroendocrine tumors (NETs) are neoplasms arising most often in the
      GI tract, pancreas, or lung. Diagnosis of NETs is often delayed until the disease
      is advanced, because of the variable and nonspecific nature of the initial
      symptoms. Surgical resection for cure is therefore not an option for most
      patients. METHODS: Somatostatin analogues represent the cornerstone of therapy
      for patients with NETs. This article reviews the important role that somatostatin
      analogues continue to play in the treatment of patients with NETs. RESULTS:
      Octreotide was the first somatostatin analogue to be developed; more than 30
      years of data have accumulated demonstrating its efficacy and safety. Lanreotide
      is another somatostatin analogue in clinical use, and pasireotide is a promising
      somatostatin analogue in development. Newer long-acting depot formulations are
      now available offering once-monthly administration. Although octreotide was
      initially developed for symptom control, recent results indicate that it also has
      an antiproliferative effect, significantly increasing time to progression in
      patients with midgut NETs. Combinations of octreotide with other targeted
      therapies may further improve patient outcomes. Findings in recent studies of the
      combination of octreotide and the mTOR inhibitor everolimus are encouraging. The
      combinations of octreotide with other agents (eg, interferon-alpha, bevacizumab,
      cetuximab, AMG-706, and sunitinib) are being investigated. CONCLUSIONS:
      Somatostatin analogues have been used to treat the symptoms of NETs for decades
      and also have an antineoplastic effect, markedly prolonging progression-free
      survival. Somatostatin analogues are likely to remain the cornerstone of
      treatment for most patients with advanced NETs. Promising new combination
      therapies are undergoing clinical investigation.

PMID- 23112885
TI  - Neoadjuvant Therapy in Clinical Stage II Pancreatic Adenocarcinoma.

PMID- 23112886
TI  - Malignant pleural mesothelioma presenting as rectal polyp: a case report and
      review of the literature.

PMID- 23112887
TI  - Durable, complete remission with bevacizumab-based chemotherapy in a patient with
      metastatic gastroesophageal junction cancer.

PMID- 23112888
TI  - Huge abdominal tumor: peritoneal solitary fibrous tumor.

PMID- 23112889
TI  - Upcoming articles.

PMID- 23112890
TI  - Family physician implementation and preventive medicine; opportunities and
      challenges.

PMID- 23112891
TI  - On the Occasion of the World Mental Health Day Minding the Gap in Mental Health:
      The Health Promotion-Primary Care-based Solution.

PMID- 23112892
TI  - Service-learning in Higher Education Relevant to the Promotion of Physical
      Activity, Healthful Eating, and Prevention of Obesity.
AB  - Service-learning is a type of experiential teaching and learning strategy
      combining classroom instruction and meaningful community service and guided
      activities for reflection. This educational approach has been used frequently in
      higher education settings, including an array of disciplines such as medicine,
      theology, public health, physical education, nutrition, psychology, anthropology,
      and sociology. The purpose of the present review paper was to provide guidance on
      the use of service-learning within higher education, relevant to the preventive
      medicine and public health topics of healthful eating, physical activity, and
      obesity prevention. In service-learning, coursework is structured to address
      community needs, and to benefit students through the real-world application of
      knowledge. The benefits for students include positive impacts on social skills,
      empathy, awareness, understanding, and concern regarding community issues, plus
      greater confidence and skills to work with diverse populations, increased
      awareness of community resources, improved motivation, and enhanced knowledge.
      Educational institutions may also benefit through improved "town and gown"
      relations, as strong ties, partnerships, and mutually beneficial activities take
      place. The present literature review describes several service-learning
      applications such as nutrition education for kids, dietary improvement for
      seniors, foodservice recipe modification on a college campus, an
      intergenerational physical activity program for nursing home residents, motor
      skill development in kindergarteners, organized elementary school recess physical
      activities, health education, and obesity prevention in children. From this
      review, service-learning appears to have great potential as a flexible component
      of academic coursework in the areas of preventive medicine and public health.

PMID- 23112893
TI  - Weight Gain during Pregnancy in Women Attending a Health Center in Isfahan City,
      Iran.
AB  - BACKGROUND: Body mass index (BMI) before pregnancy and weight gaining during
      pregnancy affect infant birth weight and are associated with unfavorable
      pregnancy outcomes. The aim of this study was to describe the weight gain pattern
      of Iranian pregnant women according to the BMI status at the beginning of
      pregnancy. METHODS: This was a longitudinal cross sectional study. A total of 500
      pregnant women in 6th-10th weeks of pregnancy were enrolled and followed up
      through delivery. Body mass index categories based on first visit weight and
      total weight gain were calculated. The multiple analysis of variance (MANOVA) was
      used to compare the mean values of gestational weight gain. RESULTS: At the first
      care, those with underweight, normal, overweight and obese accounted for 10.7%,
      46%, 35.9% and 7.4% of all participating women, respectively. Most of the
      subjects were in normal range of BMI (46%) at the beginning of the study. As BMI
      was more at the first visit, the recommended amount of weight gain was less
      achievable (70% versus 27%). Although the average weight gain in obese women was
      less than other groups (9+/-7.9), about 55% of them were over the recommended
      standards of weight gain. CONCLUSION: In conclusion, in spite of frequent visits
      during pregnancy, only half of pregnant women had normal weight gain and most of
      them had normal BMI at the first visit. This study highlights the importance of
      considering women with abnormal pre pregnancy BMI and gestational weight gain at
      an increased risk and providing appropriate care for them to prevent future
      adverse outcomes.

PMID- 23112894
TI  - Evaluation and cost analysis of national health policy of thalassaemia screening
      in west-azerbaijan province of iran.
AB  - BACKGROUND: Thalassaemia is one of the most common Mendelian disorders in
      Mediterranean area. Iran has about 26,000 Thalassaemic patients, so it is one of
      the most affected countries. The aim of this study was to evaluate the screening
      program and cost analysis of Thalassaemia prevention program in West-Azerbaijan
      province of Iran. METHODS: This study evaluated the efficacy of Health system's
      Thalassaemia prevention program with a sensitivity analysis for its costs. The
      second five years of the program was evaluated. The economic burden of
      Thalassaemia is determined by the birth prevalence of the affected infants and
      the cost that is accrued to treat the infected individuals and was compared with
      the total cost of screening the couples for thalassemia trait. RESULTS: The
      average incidence rate of major Thalassaemia was 19.8 per 100,000 live births and
      mean coverage rate of program was 74%. The rate of canceling the marriage among
      carrier couples was 53%. Cost analysis showed that the cost of screening and
      prenatal diagnosis program was much lower than the cost of treatment in potential
      thalassaemic patients. CONCLUSIONS: The prevention program of Thalassaemia
      including a premarital and pre-natal screening in west Azerbaijan province is
      demonstrated to be cost-effective. Taking some actions in order to increase the
      coverage of pre-marital screening, providing pre-natal diagnosis in private and
      public sector, complete insurance coverage for the high-risk couples to perform
      the investigations more easily, were recommended.

PMID- 23112895
TI  - The effects of various kinds of lateral wedge insoles on performance of
      individuals with knee joint osteoarthritis.
AB  - BACKGROUND: Knee joint osteoarthritis (OA) is one of the most incapacitating
      diseases affecting older population, which is associated with pain and functional
      limitation. Various kinds of conservative treatment have been used to decrease
      knee pain and to improve the quality of life of the subjects suffering from this
      disease. There are discrepancies in the clinical effects reported for the use of
      lateral wedge insole in spite of being used as one of the first conservative
      mechanical treatments for patients with medial compartments of knee OA. METHODS:
      A total of 36 subjects with medial knee compartment OA were recruited in this
      research project. Subjects were randomized into two groups to receive 3- and 7-mm
      lateral wedge insoles based on the date of birth of the participants. Some
      parameters such as severity of knee pain, Tibiofemoral angle (TFA), severity of
      OA, and quality of life were selected in this research project. RESULTS: The use
      of both 3-mm and 7-mm lateral wedge insole improves the quality of life and
      decreases knee joint pain. However, the effect of 7 mm lateral wedge insole was
      more than that of 3 mm. CONCLUSION: Using lateral wedge insole is a simple,
      inexpensive therapy for decreasing pain and improving quality of life; however,
      most research must be carried out to find the effects of lateral wedge on
      severity of knee joint OA and aligning TFA.

PMID- 23112896
TI  - Development and Evaluation of a Questionnaire for Assessment of Determinants of
      Weight Disorders among Children and Adolescents: The Caspian-IV Study.
AB  - BACKGROUND: Little experience exists on valid and reliable tools for assessment
      of the determinants of underweight and overweight in children and adolescents
      living in the Middle-East and North Africa (MENA). This study aimed to develop a
      valid and wideranging questionnaire for assessment of these parameters in a
      nationwide sample of Iranian children and adolescents. METHODS: This national
      study was conducted in 31 provinces in Iran. The first phase consisted of focus
      group discussion with 275 children and adolescents and their parents. After a
      qualitative content analysis, the initial items were extracted. In the next step,
      the face validity was assessed by expert panelists using the quantitative method
      of the Impact Score. To assess the content validity, the content validity rate
      (CVR) and the content validity index (CVI) were determined. The internal
      consistency was examined by Cronbach alpha, and its test-retest reliability was
      determined. The socio-demographic variables, perinatal factors, lifestyle
      factors, family history, knowledge and attitude were assessed. Dietary intakes
      were assessed by a validated 168-item semi-quantitative food frequency
      questionnaire. A validated questionnaire for quality of life was filled in
      anonymously. RESULTS: A team of expert researchers conducted the data analysis of
      576 interviews by using qualitative content analysis method. The analysis process
      began by determining the semantic units about the concepts studied. The initial
      questionnaire was developed in four domains by including Likert scale questions.
      In the face validity step, all questions of the primary questionnaire obtained a
      score of more than 1.5. In the phase of CVR assessment, 6 questions obtained a
      score of less than 0.62, and were omitted. The rest of questions were assessed
      for CVI, and got a score of more than 0.75. Cronbach's alpha coefficient of the
      whole questionnaire was 0.97, and the Pearson correlation coefficient of the test
      retest phase was 0.94. CONCLUSION: The developed questionnaire is a valid and
      reliable tool for assessment of the determinants of weight disorders in a
      nationally representative sample of children and adolescents in the MENA.

PMID- 23112897
TI  - The Effect of Different Intrathecal Doses of Meperidine on Shivering during
      Delivery Under Spinal Anesthesia.
AB  - BACKGROUND: This study was performed to compare the effect of different doses of
      intrathecal meperidine on the incidence and intensity of shivering and other side
      effects after spinal anesthesia for cesarean delivery. METHODS: One hundred and
      fifty-six parturient women scheduled for elective cesarean delivery were enrolled
      in four groups. Spinal anesthesia consisted of heavy bupivacaine 0.5% (10 mg) in
      the standard group (Group I), heavy bupivacaine 0.5% (10 mg) plus meperidine (0.2
      mg per kg) in Group II, heavy bupivacaine 0.5% (10 mg) plus meperidine (0.3 mg
      per kg) in Group III, heavy bupivacaine 0.5% (10 mg) plus meperidine (0.4 mg per
      kg) in Group IV. The signs and symptoms were recorded by an observer unaware of
      the study groups. Data were analyzed using analysis of variance, Kruskal-Wallis H
      test and chi-square. A P value less than 0.05 was considered to be significant.
      RESULTS: The systolic blood pressure, amount of bleeding, Pulse Rate, O2
      saturation, neonatal apgar scores, core temperatures and sensory level revealed
      no difference between groups (P>0.05). The incidence (47.5%, 37.5%, 27.5% and
      15.0%, respectively) and intensity of shivering decreased as the dose of
      meperidine increased (P=0.002) but the incidence of nausea and vomiting (8.0%,
      15.4%, 25.9% and 35.8%, respectively) (P=0.000) and pruritis (25.64, 28.21,
      38.46, and 48.72 respectively) increased as the dose of meperidine increased
      (P=0.000). CONCLUSION: The high dose of intrathecal meperidine is effective in
      reducing the incidence and intensity of shivering associated with spinal
      anesthesia for cesarean delivery but the high incidence of nausea and vomiting is
      unpleasant for the patient and can be a major problem with a high dose of
      meperdine.

PMID- 23112898
TI  - Clients' satisfaction with primary health care in muscat.
AB  - BACKGROUND: To measure clients' satisfaction with primary health care in the
      capital of Oman, Muscat, and also to identify the factors affecting their
      satisfaction. METHODS: Through a cross-sectional study in health centers, 400
      participants during the period from November 2009 to February 2010 were
      interviewed about their satisfaction degree with the primary health care services
      and setting. Four urban primary health care clinics from Muscat were selected
      randomly. Six domains of satisfaction including accessibility to services,
      continuity of care, humaneness of staff, comprehensiveness of care, provision of
      health education, and effectiveness of services were calculated from selected
      variables. The mean score of each area were calculated and then divided by the
      number of items in each area. Finally satisfaction areas were ranked based on
      recent criteria. RESULTS: Mean age was 29.5 years (SD = 9.37) for male and 26.01
      years (SD = 7.12) for female participants. All the areas were suitable and only
      continuity of care had negative score. The ranked areas of satisfaction were as
      humanness of staff, effectiveness of services, access to services, provision of
      health educational materials, comprehensiveness of care, continuity of care.
      CONCLUSIONS: Primary health care were accepted as a suitable strategy for
      providing health care among clients of urban health centers of Muscat. It can be
      recommended to other countries to use this as a choice for health care provision.

PMID- 23112899
TI  - Comparative Study of Two Silicone Hydrogel Contact Lenses used as Bandage Contact
      Lenses after Photorefractive Keratectomy.
AB  - BACKGROUND: Silicon hydrogel bandage contact lenses are used to enhance
      epithelial healing, control surface-generated pain, and prevent epithelial
      erosions after refractive surgery. Considering the importance of faster
      reepithelialization in preventing complications of photorefractive keratectomy
      (PRK) and the fact that the features and specifications of these commercially
      available lenses are different and their performance as a postoperative bandage
      lenses would be different also, the aim of this study was comparison the efficacy
      of senofilcon A and lotrafilcon A after PRK. METHODS: In this prospective study,
      44 patients with PRK in both eyes randomly received a silicon hydrogel contact
      lens of senofilcon A in one eye and lotrafilcon A in other eye. Then the
      epithelial defect size, visual acuity and subjective level of pain and discomfort
      were measured for both eyes and compared on day 1, 3 and 5 postoperatively.
      RESULTS: There was no statistical difference in rate of reepithelialization
      between senofilcon A and lotrafilcon A (P > 0.05). The mean pain and discomfort
      index was significantly lower in eyes with senofilcon A (P < 0.05). The mean
      subjective visual scores were similar with both bandage contact lenses (BCLs) (P
      > 0.05). CONCLUSION: Silicon hydrogel BCLs are safe and effective for corneal
      reepithelialization and have great therapeutic outcome on visual outcomes after
      PRK. But, senofilcon A had better effect on postoperative pain and discomfort
      which made it superior than lotrafilcon A. However for more conclusive results,
      it is recommended to study larger sample size with evaluation the possible
      factors responsible for the obtained findings regarding postoperative pain and
      discomfort.

PMID- 23112900
TI  - Environmental air pollution and acute cerebrovascular complications: an ecologic
      study in tehran, iran.
AB  - BACKGROUND: In this study, we aimed to assess the association between air
      pollution and cerebrovascular complications in Tehran, one of the most air
      polluted cities in the world, among different subgroups of patients with stroke
      in 2004. METHODS: In this ecologic study, we calculated the daily average levels
      of different air pollutants including CO, NO(X), SO(2), O(3), and PM(10) and also
      humidity and temperature on the day of stroke and 48 hours prior to stroke in 1
      491 patients admitted with the diagnosis of stroke in eight referral hospitals in
      different areas of Tehran. Then, we evaluated the association between the rate of
      stroke admissions and the level of the selected pollutants, humidity, and
      temperature on the day of stroke and 48 hours prior to stroke among different
      subgroups of patients. RESULTS: There was no significant association between the
      same-day level of the pollutants and the rate of stroke admissions, but an
      association was seen for their level 48 hours before stroke. These associations
      differed among different subgroups of age, sex, history of underlying diseases,
      and type of stroke. Same-day temperature had a reverse association in patients
      with hemorrhagic stroke and in patients without a history of heart disease or
      previous stroke. A direct significant association was seen for humidity level 48
      hours before stroke in patients with a history of heart disease. CONCLUSIONS: It
      is inferred that air pollution has a direct association with the incidence of
      stroke and these association differs among different subgroups of patients. The
      results of this study are not time-dependant and can be generalized to different
      times and regions. Moreover, these results may be useful for environmental health
      policy makers.

PMID- 23112901
TI  - Disease Burden Assessment Beyond In-patient Data: A Morbidity Profile Assessment
      of Outpatients.
AB  - BACKGROUND: Global disease burden estimates often lack real data on morbidities,
      especially from patients treated in Outpatient Department (OPD). In Sri Lanka,
      around 40 million visits are made annually to the OPDs in government hospitals
      and we conducted a preliminary study to assess the morbidity profile of these OPD
      patients. METHODS: Patients attending the OPD, in teaching hospital Peradeniya,
      Sri Lanka, was recruited into the study using systematic random sampling
      procedure. A self-administered, structured questionnaire was used to collect
      data. Investigators explained the study to patients and data collection was
      completed before seeing the physician. Self-reported presenting complain was used
      to analyze the morbidity profile of the patients. RESULTS: The study sample
      consisted of 1 439 patients (male - 515, female - 924). The mean age of the study
      sample was 40 years (SD = 19 years). The mean age of the females were
      statistically significantly higher than that of the males (t = 4.03, P<0.001).
      Housewives constituted the major occupational group (52%) followed by students
      (15.9%). The most common presenting complains reported were body aches and pains
      (15.6%), cough and cold (10.5%), and abdominal pain (8.5%). Leading cause of
      hospital visit among different demographic categories showed statistically
      significant variations. CONCLUSIONS: The morbidity pattern observed in this
      patient population was not previously reported. OPD surveillance should be
      established to understand the changing pattern of minor ailments which might have
      a huge impact on health of the public.

PMID- 23112902
TI  - Vitamin d deficiency, prevention and treatment.

PMID- 23112903
TI  - "Catch Them before it Becomes Too Late"-Oral Cancer Detection. Report of Two
      Cases and Review of Diagnostic AIDS in Cancer Detection.
AB  - Most oral and oropharyngeal squamous cell carcinomas (OOSCCs) are in advanced
      stages at diagnosis, and treatment does not improve survival rates. Early
      recognition and diagnosis of OOSCCs might improve patient survival and reduce
      treatment-related morbidity. The purpose of this article is to create awareness
      among the general practitioners to recognize the premalignant and early malignant
      lesions and to review the different diagnostic aids for the detection of cancer.

PMID- 23112904
TI  - Assessment of Head Circumference among Pre-school Children of Midnapore Town,
      West Bengal using WHO (2007) Recommended Cut-off Points.

PMID- 23112905
TI  - Celiac disease and abnormal liver function test.

PMID- 23112906
TI  - An assessment of the impact of fortification of staples and condiments on
      micronutrient intake in young Vietnamese children.
AB  - Targeted fortification programs for infants and young children are an effective
      strategy to prevent micronutrient deficiencies in developing countries, but the
      role of large-scale fortification of staple foods and condiments is less clear.
      Dietary modeling in children aged 6-60 months was undertaken, based on food
      consumption patterns described in the 2009 national food consumption survey,
      using a 24-h recall method. Consumption data showed that the median intake of a
      child for iron, vitamin A and zinc, as a proportion of the Vietnamese Recommended
      Dietary Allowance (VRDA), is respectively 16%-48%, 14%-49% and 36%-46%,
      (depending on the age group). Potential fortification vehicles, such as rice,
      fish/soy sauces and vegetable oil are consumed daily in significant amounts
      (median: 170 g/capita/day, 4 g/capita/day and 6 g/capita/day, respectively) by
      over 40% of the children. Vegetable oil fortification could contribute to an
      additional vitamin A intake of 21%-24% of VRDA recommended nutrient intake, while
      fortified rice could support the intakes of all the other micronutrients (14%-61%
      for iron, 4%-11% for zinc and 33%-49% of folate requirements). Other food
      vehicles, such as wheat flour, which is consumed by 16% of children, could also
      contribute to efforts to increase micronutrient intakes, although little impact
      on the prevalence of micronutrient deficiencies can be expected if used alone.
      The modeling suggests that fortification of vegetable oil, rice and sauces would
      be an effective strategy to address micronutrient gaps and deficiencies in young
      children.

PMID- 23112907
TI  - Effects of glycerol and creatine hyperhydration on doping-relevant blood
      parameters.
AB  - Glycerol is prohibited as an ergogenic aid by the World Anti-Doping Agency (WADA)
      due to the potential for its plasma expansion properties to have masking effects.
      However, the scientific basis of the inclusion of Gly as a "masking agent"
      remains inconclusive. The purpose of this study was to determine the effects of a
      hyperhydrating supplement containing Gly on doping-relevant blood parameters.
      Nine trained males ingested a hyperhydrating mixture twice per day for 7 days
      containing 1.0 g.kg(-1) body mass (BM) of Gly, 10.0 g of creatine and 75.0 g of
      glucose. Blood samples were collected and total hemoglobin (Hb) mass determined
      using the optimized carbon monoxide (CO) rebreathing method pre- and post
      supplementation. BM and total body water (TBW) increased significantly following
      supplementation by 1.1 +/- 1.2 and 1.0 +/- 1.2 L (BM, P < 0.01; TBW, P <0.01),
      respectively. This hyperhydration did not significantly alter plasma volume or
      any of the doping-relevant blood parameters (e.g., hematocrit, Hb, reticulocytes
      and total Hb-mass) even when Gly was clearly detectable in urine samples. In
      conclusion, this study shows that supplementation with hyperhydrating solution
      containing Gly for 7 days does not significantly alter doping-relevant blood
      parameters.

PMID- 23112909
TI  - Assessing the relationship between vitamin D3 and stratum corneum hydration for
      the treatment of xerotic skin.
AB  - Vitamin D(3) has been called the "sunshine" vitamin since the formation of
      vitamin D is mediated by exposure to sunlight. Vitamin D(3) is linked to many
      health benefits, however serum levels of vitamin D(3) have been decreasing over
      the last few decades and the lower levels of vitamin D(3) may have consequences
      on normal physiology. We investigated the association between serum 25
      hydroxyvitamin D (25(OH)D) levels and stratum corneum conductance as well as the
      effect of topical application of cholecalciferol (vitamin D(3)) on dry skin.
      Eighty three subjects were recruited and blood serum levels and skin conductance
      measurements were taken after a one week washout. A correlation was observed
      between vitamin D levels and skin moisture content, individuals with lower levels
      of vitamin D had lower average skin moisture. Subsequently, a 3-week split leg,
      randomized, vehicle controlled clinical study was conducted on a subset of 61 of
      the above individuals who were identified with non-sufficient vitamin D serum
      levels. Topical supplementation with cholecalciferol significantly increased
      measurements of skin moisturization and resulted in improvements in subjective
      clinical grading of dry skin. Taken together our finding suggest a relationship
      between serum vitamin D(3) (25(OH)D) levels and hydration of the stratum corneum
      and further demonstrate the skin moisture benefit from topical application of
      vitamin D(3).

PMID- 23112908
TI  - Exercise-induced immunodepression in endurance athletes and nutritional
      intervention with carbohydrate, protein and fat-what is possible, what is not?
AB  - Heavily exercising endurance athletes experience extreme physiologic stress,
      which is associated with temporary immunodepression and higher risk of infection,
      particularly upper respiratory tract infections (URTI). The aim of this review is
      to provide a critical up-to-date review of existing evidence on the
      immunomodulatory potential of selected macronutrients and to evaluate their
      efficacy. The results of 66 placebo-controlled and/or crossover trials were
      compared and analysed. Among macronutrients, the most effective approach to
      maintain immune function in athletes is to consume >=6% carbohydrate during
      prolonged exercise. Because inadequate nutrition affects almost all aspects of
      the immune system, a well-balanced diet is also important. Evidence of beneficial
      effects from other macronutrients is scarce and results are often inconsistent.
      Using a single nutrient may not be as effective as a mixture of several
      nutritional supplements. Due to limited research evidence, with the exception of
      carbohydrate, no explicit recommendations to reduce post-exercise URTI symptoms
      with single macronutrients can be derived.

PMID- 23112910
TI  - Intake of dairy products in relation to periodontitis in older Danish adults.
AB  - This cross-sectional study investigates whether calcium intakes from dairy and
      non-dairy sources, and absolute intakes of various dairy products, are associated
      with periodontitis. The calcium intake (mg/day) of 135 older Danish adults was
      estimated by a diet history interview and divided into dairy and non-dairy
      calcium. Dairy food intake (g/day) was classified into four groups: milk, cheese,
      fermented foods and other foods. Periodontitis was defined as the number of teeth
      with attachment loss >=3 mm. Intakes of total dairy calcium (Incidence-rate ratio
      (IRR) = 0.97; p = 0.021), calcium from milk (IRR = 0.97; p = 0.025) and fermented
      foods (IRR = 0.96; p = 0.03) were inversely and significantly associated with
      periodontitis after adjustment for age, gender, education, sucrose intake,
      alcohol consumption, smoking, physical activity, vitamin D intake, heart disease,
      visits to the dentist, use of dental floss and bleeding on probing, but non-dairy
      calcium, calcium from cheese and other types of dairy food intakes were not.
      Total dairy foods (IRR = 0.96; p = 0.003), milk (IRR = 0.96; p = 0.028) and
      fermented foods intakes (IRR = 0.97; p = 0.029) were associated with reduced risk
      of periodontitis, but cheese and other dairy foods intakes were not. These
      results suggest that dairy calcium, particularly from milk and fermented
      products, may protect against periodontitis. Prospective studies are required to
      confirm these findings.

PMID- 23112911
TI  - The role of the enteral route and the composition of feeds in the nutritional
      support of malnourished surgical patients.
AB  - In surgical patients, malnutrition is an important risk factor for post-operative
      complications. In undernourished patients undergoing major gastrointestinal
      procedures, preoperative enteral nutrition (EN) should be preferred whenever
      feasible. It may be given either orally or by feeding tubes, depending on patient
      compliance. Early oral intake after surgery should be encouraged, but if an
      insufficient postoperative oral intake is anticipated, tube feeding should be
      initiated as soon as possible. The use of immunomodulating formulas offers
      significant advantages when compared to standard feeds and the positive results
      on postoperative complications seem independent from the baseline nutritional
      status. In malnourished patients, the optimal timing and dose of immunonutrition
      is unclear, but consistent data suggest that they should be treated peri
      operatively for at least two weeks.

PMID- 23112912
TI  - Different dietary protein and PUFA interventions alter the fatty acid
      concentrations, but not the meat quality, of porcine muscle.
AB  - The present study investigated the effect of a reduced protein diet in
      combination with different vegetable oils (sunflower seed oil or linseed oil) on
      carcass traits, meat quality and fatty acid profile in porcine muscle. Forty male
      Landrace pigs were allocated into four experimental groups (each n = 8) and one
      control group (n = 8) at a live weight of approximately 60 kg. The pigs were fed
      ad libitum from 60 kg to 100 kg live weight and restricted to 2.8 kg/day until
      they reached 120 kg. In contrast to other studies, the intramuscular fat content
      (IMF) did not increase in animals of groups fed a reduced protein diet and
      vegetable oils. The IMF ranged between 1.2% and 1.4%. The growth performance and
      meat quality of the longissimus muscle was not affected by the diet, but the
      average daily gain (ADG) and drip loss were affected. The muscle fatty acid
      concentrations were significantly affected by the diet, resulting in higher n-3
      FA concentrations up to 113 mg/100 g muscle and lower n-6/n-3 PUFA ratio for pigs
      fed linseed oil-containing high- and reduced protein diets, compared to sunflower
      seed oil-containing diets.

PMID- 23112913
TI  - Selenium, selenoprotein genes and Crohn's disease in a case-control population
      from Auckland, New Zealand.
AB  - New Zealand has one of the highest incidence rates of Crohn's Disease (CD),
      whilst the serum selenium status of New Zealanders is amongst the lowest in the
      world. A prospective case-control study in Auckland, New Zealand considered serum
      selenium as a potential CD risk factor. Serum selenium levels were significantly
      lower in CD patients compared to controls (101.8 +/- 1.02 vs. 111.1 +/- 1.01
      ng/mL) (p = 5.91 * 10(-8)). Recent detailed studies in the United Kingdom have
      suggested an optimal serum level around 122 ng/mL, making the average CD patient
      in New Zealand selenium deficient. Of the 29 single nucleotide polymorphisms
      (SNPs) tested, 13 were found to significantly interact with serum selenium on CD.
      After adjustment for multiple testing, a significant interaction with serum
      selenium on CD was found for three SNPs, namely rs17529609 and rs7901303 in the
      gene SEPHS1, and rs1553153 in the gene SEPSECS. These three SNPs have not been
      reported elsewhere as being significantly associated with selenium or CD. It is
      unclear as to whether lower selenium levels are a cause or an effect of the
      disease.

PMID- 23112914
TI  - Body-related social comparison and disordered eating among adolescent females
      with an eating disorder, depressive disorder, and healthy controls.
AB  - The purpose of this study was to investigate the association between body-related
      social comparison (BRSC) and eating disorders (EDs) by: (a) comparing the degree
      of BRSC in adolescents with an ED, depressive disorder (DD), and no psychiatric
      history; and (b) investigating whether BRSC is associated with ED symptoms after
      controlling for symptoms of depression and self-esteem. Participants were 75
      girls, aged 12-18 (25 per diagnostic group). To assess BRSC, participants
      reported on a 5-point Likert scale how often they compare their body to others'.
      Participants also completed a diagnostic interview, Eating Disorders Inventory-2
      (EDI-2), Beck Depression Inventory-II (BDI-II), and Rosenberg Self-Esteem Scale
      (RSE). Compared to adolescents with a DD and healthy adolescents, adolescents
      with an ED engaged in significantly more BRSC (p <= 0.001). Collapsing across
      groups, BRSC was significantly positively correlated with ED symptoms (p <=
      0.01), and these associations remained even after controlling for two robust
      predictors of both ED symptoms and social comparison, namely BDI-II and RSE. In
      conclusion, BRSC seems to be strongly related to EDs. Treatment for adolescents
      with an ED may focus on reducing BRSC.

PMID- 23112915
TI  - Low zinc status and absorption exist in infants with jejunostomies or ileostomies
      which persists after intestinal repair.
AB  - There is very little data regarding trace mineral nutrition in infants with small
      intestinal ostomies. Here we evaluated 14 infants with jejunal or ileal ostomies
      to measure their zinc absorption and retention and biochemical zinc and copper
      status. Zinc absorption was measured using a dual-tracer stable isotope technique
      at two different time points when possible. The first study was conducted when
      the subject was receiving maximal tolerated feeds enterally while the ostomy
      remained in place. A second study was performed as soon as feasible after full
      feeds were achieved after intestinal repair. We found biochemical evidence of
      deficiencies of both zinc and copper in infants with small intestinal ostomies at
      both time points. Fractional zinc absorption with an ostomy in place was 10.9% +/
      5.3%. After reanastamosis, fractional zinc absorption was 9.4% +/- 5.7%. Net
      zinc balance was negative prior to reanastamosis. In conclusion, our data
      demonstrate that infants with a jejunostomy or ileostomy are at high risk for
      zinc and copper deficiency before and after intestinal reanastamosis. Additional
      supplementation, especially of zinc, should be considered during this time
      period.

PMID- 23112916
TI  - Comparison of glucose monitoring methods during steady-state exercise in women.
AB  - Data from Continuous Glucose Monitoring (CGM) systems may help improve overall
      daily glycemia; however, the accuracy of CGM during exercise remains
      questionable. The objective of this single group experimental study was to
      compare CGM-estimated values to venous plasma glucose (VPG) and capillary plasma
      glucose (CPG) during steady-state exercise. Twelve recreationally active females
      without diabetes (aged 21.8 +/- 2.4 years), from Central Washington University
      completed the study. CGM is used by individuals with diabetes, however the
      purpose of this study was to first validate the use of this device during
      exercise for anyone. Data were collected between November 2009 and April 2010.
      Participants performed two identical 45-min steady-state cycling trials (~60%
      P(max)) on non-consecutive days. Glucose concentrations (CGM-estimated, VPG, and
      CPG values) were measured every 5 min. Two carbohydrate gel supplements along
      with 360 mL of water were consumed 15 min into exercise. A product-moment
      correlation was used to assess the relationship and a Bland-Altman analysis
      determined error between the three glucose measurement methods. It was found that
      the CGM system overestimated mean VPG (mean absolute difference 17.4 mg/dL (0.97
      mmol/L)) and mean CPG (mean absolute difference 15.5 mg/dL (0.86 mmol/L)). Bland
      Altman analysis displayed wide limits of agreement (95% confidence interval) of
      44.3 mg/dL (2.46 mmol/L) (VPG compared with CGM) and 41.2 mg/dL (2.29 mmol/L)
      (CPG compared with CGM). Results from the current study support that data from
      CGM did not meet accuracy standards from the 15197 International Organization for
      Standardization (ISO).

PMID- 23112917
TI  - Enteral nutrition for feeding severely underfed patients with anorexia nervosa.
AB  - Severe undernutrition nearly always leads to marked changes in body spaces (e.g.,
      alterations of intra-extracellular water) and in body masses and composition
      (e.g., overall and compartmental stores of phosphate, potassium, and magnesium).
      In patients with severe undernutrition it is almost always necessary to use oral
      nutrition support and/or artificial nutrition, besides ordinary food; enteral
      nutrition should be a preferred route of feeding if there is a functional
      accessible gastrointestinal tract. Refeeding of severely malnourished patients
      represents two very complex and conflicting tasks: (1) to avoid "refeeding
      syndrome" caused by a too fast correction of malnutrition; (2) to avoid
      "underfeeding" caused by a too cautious rate of refeeding. The aim of this paper
      is to discuss the modality of refeeding severely underfed patients and to present
      our experience with the use of enteral tube feeding for gradual correction of
      very severe undernutrition whilst avoiding refeeding syndrome, in 10 patients
      aged 22 +/- 11.4 years and with mean initial body mass index (BMI) of 11.2 +/-
      0.7 kg/m(2). The mean BMI increased from 11.2 +/- 0.7 kg/m(2) to 17.3 +/- 1.6
      kg/m(2) and the mean body weight from 27.9 +/- 3.3 to 43.0 +/- 5.7 kg after 90
      days of intensive in-patient treatment (p < 0.0001). Caloric intake levels were
      established after measuring resting energy expenditure by indirect calorimetry,
      and nutritional support was performed with enteral feeding. Vitamins, phosphate,
      and potassium supplements were administered during refeeding. All patients
      achieved a significant modification of BMI; none developed refeeding syndrome. In
      conclusion, our findings show that, even in cases of extreme undernutrition,
      enteral feeding may be a well-tolerated way of feeding.

PMID- 23112918
TI  - Hypocholesterolemic effects of lactic acid-fermented soymilk on rats fed a high
      cholesterol diet.
AB  - The effect of fermented soymilk on rats fed a high cholesterol diet was
      investigated to clarify the cholesterol-lowering function. Male Sprague-Dawley
      rats aged 7 weeks were fed a control diet (1% cholesterol, high cholesterol
      diet), high cholesterol diet containing 11.7% fermented soymilk diet (5% soy
      protein as final concentration, F-5), or high cholesterol diet containing 23.4%
      fermented soymilk diet (10% soy protein as final concentration, F-10) for 5
      weeks. The liver weight and fat mass were decreased by the ingestion of fermented
      soymilk. The hepatic triglyceride and cholesterol levels in the F-5 and F-10
      groups were significantly lowered compared to those in the control group. The
      plasma total cholesterol level of the F-10 group was significantly decreased. The
      expression of SREBP-2, a cholesterol synthesis-related gene, was significantly
      decreased in liver of the F-5 group, but the expression of CYP7a1, a cholesterol
      catabolism-related gene, was significantly increased. These results suggest that
      fermented soymilk can modulate the cholesterol metabolism in rats fed a high
      cholesterol diet.

PMID- 23112919
TI  - Poor knowledge and practices related to iodine nutrition during pregnancy and
      lactation in Australian women: pre- and post-iodine fortification.
AB  - A before-after review was undertaken to assess whether knowledge and practices
      related to iodine nutrition, supplementation and fortification has improved in
      Australian women since the introduction of mandatory iodine fortification in
      2009. Surveys of pregnant (n = 139) and non-pregnant (n = 75) women in 2007-2008
      are compared with surveys of pregnant (n = 147) and lactating women (n = 60) one
      to two years post-fortification in a regional area of New South Wales, Australia.
      A self-administered questionnaire was completed and dietary intake of iodine was
      assessed using a validated food frequency questionnaire. A generally poor
      knowledge about the role and sources of iodine in the diet remained after
      fortification. Post-fortification, iodine-containing supplements were being taken
      by 60% (up from 20% pre-fortification) and 45% of pregnant and lactating women,
      respectively. Dairy foods were the highest contributors to dietary iodine intake
      (57%-62%). A low intake of fish and seafood resulted in this food group
      contributing only 3%-8% of total intake. A low level of public awareness
      regarding the role of iodine in health supports the need for public health
      strategies in addition to fortification, such as an accompanying consumer
      education campaign, increased uptake of supplementation, and on-going monitoring.

PMID- 23112920
TI  - Effects of two different levels of dietary protein on body composition and
      protein nutritional status of growing rats.
AB  - This study aimed to investigate the effect of a high-protein diet on growth, body
      composition, and protein nutritional status of young rats. Newly-weaned Wistar
      rats, weighing 45-50 g, were distributed in two experimental groups, according to
      their diets, which contained 12% (G12) or 26% protein (G26), over a period of 3
      weeks. The animals were euthanized at the end of this period and the following
      analyses were performed: chemical composition of the carcass, proteoglycan
      synthesis, IGF-I concentration (serum, muscle and cartilage), total tissue RNA,
      protein concentration (muscle and cartilage) and protein synthesis (muscle and
      cartilage). The high-protein diet was found to result in a higher fat-free mass
      and lower fat mass in the carcass, with no difference in growth or protein
      nutritional status.

PMID- 23112921
TI  - Consequences of essential fatty acids.
AB  - Essential fatty acids (EFA) are nutrients that form an amazingly large array of
      bioactive mediators that act on a large family of selective receptors. Nearly
      every cell and tissue in the human body expresses at least one of these
      receptors, allowing EFA-based signaling to influence nearly every aspect of human
      physiology. In this way, the health consequences of specific gene-environment
      interactions with these nutrients are more extensive than often recognized. The
      metabolic transformations have similar competitive dynamics for the n-3 and n-6
      homologs when converting dietary EFA from the external environment of foods into
      the highly unsaturated fatty acid (HUFA) esters that accumulate in the internal
      environment of cells and tissues. In contrast, the formation and action of
      bioactive mediators during tissue responses to stimuli tend to selectively create
      more intense consequences for n-6 than n-3 homologs. Both n-3 and n-6 nutrients
      have beneficial actions, but many common health disorders are undesired
      consequences of excessive actions of tissue n-6 HUFA which are preventable. This
      review considers the possibility of preventing imbalances in dietary n-3 and n-6
      nutrients with informed voluntary food choices. That action may prevent the
      unintended consequences that come from eating imbalanced diets which support
      excessive chronic actions of n-6 mediators that harm human health. The
      consequences from preventing n-3 and n-6 nutrient imbalances on a nationwide
      scale may be very large, and they need careful evaluation and implementation to
      avoid further harmful consequences for the national economy.

PMID- 23112923
TI  - Renovating the history of the korean journal of orthodontics.

PMID- 23112922
TI  - Deterministic separation of cancer cells from blood at 10 mL/min.
AB  - Circulating tumor cells (CTCs) and circulating clusters of cancer and stromal
      cells have been identified in the blood of patients with malignant cancer and can
      be used as a diagnostic for disease severity, assess the efficacy of different
      treatment strategies and possibly determine the eventual location of metastatic
      invasions for possible treatment. There is thus a critical need to isolate,
      propagate and characterize viable CTCs and clusters of cancer cells with their
      associated stroma cells. Here, we present a microfluidic device for mL/min flow
      rate, continuous-flow capture of viable CTCs from blood using deterministic
      lateral displacement (DLD) arrays. We show here that a DLD array device can
      isolate CTCs from blood with capture efficiency greater than 85% CTCs at
      volumetric flow rates of up to 10 mL/min with no effect on cell viability.

PMID- 23112924
TI  - Reader's Forum.

PMID- 23112925
TI  - Effect of surface anodization on stability of orthodontic microimplant.
AB  - OBJECTIVE: To determine the effect of surface anodization on the interfacial
      strength between an orthodontic microimplant (MI) and the rabbit tibial bone,
      particularly in the initial phase after placement. METHODS: A total of 36 MIs
      were driven into the tibias of 3 mature rabbits by using the self-drilling method
      and then removed after 6 weeks. Half the MIs were as-machined (n = 18; machined
      group), while the remaining had anodized surfaces (n = 18; anodized group). The
      peak insertion torque (PIT) and the peak removal torque (PRT) values were
      measured for the 2 groups of MIs. These values were then used to calculate the
      interfacial shear strength between the MI and cortical bone. RESULTS: There were
      no statistical differences in terms of PIT between the 2 groups. However, mean
      PRT was significantly greater for the anodized implants (3.79 +/- 1.39 Ncm) than
      for the machined ones (2.05 +/- 1.07 Ncm) (p < 0.01). The interfacial strengths,
      converted from PRT, were calculated at 10.6 MPa and 5.74 MPa for the anodized and
      machined group implants, respectively. CONCLUSIONS: Anodization of orthodontic
      MIs may enhance their early-phase retention capability, thereby ensuring a more
      reliable source of absolute anchorage.

PMID- 23112926
TI  - The relationship between malocclusion and menarcheal age, and its secular trend
      for Korean women.
AB  - OBJECTIVE: This study aimed to evaluate the mean age of menarche, its secular
      trend in Korean women, and the relationship between malocclusion and the rate of
      skeletal maturation, as defined by menarcheal age. METHODS: We retrospectively
      collected data on menarcheal age from 931 Korean women born during 1961 - 1997.
      Subjects were divided by the malocclusion type and birth-year decade into 3 and 4
      groups, respectively. The mean menarcheal age for each group was determined, and
      one-way ANOVA was performed for intergroup comparison (p = 0.05). Two-way ANOVA
      was also performed to compare all the 12 subgroups (p = 0.05). RESULTS: The mean
      age of menarche was 12.82 years for Korean women born during 1961 - 1997. A
      distinct downward secular trend of menarcheal age was noticed (p < 0.05). For the
      birth-year decade 1961 - 1970, the Class III malocclusion group showed earlier
      onset of menarche than the other malocclusion groups (p < 0.05), but the other
      birth-year groups did not show any significant difference in the type of
      malocclusion (p > 0.05). CONCLUSIONS: A positive secular trend towards earlier
      menarche exists among Korean women. Malocclusion does not show any significant
      relationship with the rate of skeletal maturation, as defined by menarcheal age.

PMID- 23112927
TI  - Effects of demineralizaton-inhibition procedures on the bond strength of brackets
      bonded to demineralized enamel surface.
AB  - OBJECTIVE: To study and compare the effects of different demineralization
      inhibition methods on the shear bond strength (SBS) and fracture mode of an
      adhesive used to bond orthodontic brackets to demineralized enamel surfaces.
      METHODS: Eighty freshly extracted, human maxillary premolars were divided into 4
      equal groups and demineralized over the course of 21 days. Brackets were bonded
      to the demineralized enamel of teeth in Group 1. In Group 2, bonding was
      performed following resin infiltration (ICON(r), DMG, Hamburg, Germany). Before
      bonding, pre-treatment with acidulated phosphate fluoride (APF) or solutions
      containing casein phosphopeptide-amorphous calcium phosphate with 2% neutral
      sodium fluoride (CPP-ACP/wF) was performed in Groups 3 and 4, respectively. The
      SBS values of the brackets were measured and recorded following mechanical
      shearing of the bracket from the tooth surface. The adhesive remnant index (ARI)
      scores were determined after the brackets failed. Statistical comparisons were
      performed using one-way ANOVA, Tukey's post-tests, and G-tests. RESULTS:
      Significant differences were found in some of the intergroup comparisons of the
      SBS values (F = 39.287, p < 0.001). No significant differences were found between
      the values for the APF-gel and control groups, whereas significantly higher SBS
      values were recorded for the resin-infiltrated and CPP-ACP/wF-treated groups. The
      ARI scores were also significantly different among the 4 groups (p < 0.001).
      CONCLUSIONS: Tooth surfaces exposed to resin infiltration and CPP-ACP/wF
      application showed higher debonding forces than the untreated, demineralized
      surfaces.

PMID- 23112928
TI  - Facial soft tissue thickness among skeletal malocclusions: is there a difference?
AB  - OBJECTIVE: The purpose of this study was to determine the soft tissue thickness
      of male and female orthodontic patients with different skeletal malocclusions.
      METHODS: Soft tissue thickness measurements were made on lateral cephalometric
      radiographs of 180 healthy orthodontic patients with different skeletal
      malocclusions (Class I: 60 subjects, Class II: 60 subjects, Class III: 60
      subjects). Ten measurements were analyzed. For statistical evaluation, one-way
      ANOVA and Kruskal-Wallis tests were performed. Least significant difference (LSD)
      and Dunnet T3 post hoc tests were used to determine the individual differences.
      RESULTS: Soft tissue thicknesses were found to be greater for men than for women.
      Statistically significant differences among the skeletal groups were found in
      both men and women at the following sites: labrale superius, stomion, and labrale
      inferius. The thickness at the labrale superius and stomion points in each
      skeletal type was the greatest in Class III for both men and women. On the other
      hand, at the labrale inferius point, for both men and women, soft tissue depth
      was the least in Class III and the greatest in Class II. CONCLUSIONS: Soft tissue
      thickness differences among skeletal malocclusions were observed at the labrale
      superius, stomion, and labrale inferius sites for both men and women.

PMID- 23112929
TI  - Evaluation of different enamel conditioning techniques for orthodontic bonding.
AB  - OBJECTIVE: The aim of this study was to compare the effects of different enamel
      conditioning techniques for bracket bonding. METHODS: Ninety-one human premolars
      were randomly divided in six groups of 15 specimens each. The enamel surfaces of
      the teeth were etched with 35% orthophosphoric acid in Group 1, with a self
      etching primer in Group 2, sandblasted in Group 3, sandblasted and etched with
      35% orthophosphoric acid in Group 4, conditioned by Er:YAG laser in Group 5 and
      conditioned by Er:YAG laser and etched with 35% phosphoric acid gel respectively
      in Group 6. After enamel conditioning procedures, brackets were bonded and shear
      bonding test was performed. After debonding, adhesive remnant index scores were
      calculated for all groups. One tooth from each group were inspected by scanning
      electron microscope for evaluating the enamel surface characteristics. RESULTS:
      The laser and acid etched group showed the highest mean shear bond strength (SBS)
      value (13.61 +/- 1.14 MPa) while sandblasted group yielded the lowest value (3.12
      +/- 0.61 MPa). CONCLUSIONS: Although the SBS values were higher, the teeth in
      laser conditioned groups were highly damaged. Therefore, acid etching and self
      etching techniques were found to be safer for orthodontic bracket bonding.
      Sandblasting method was found to generate inadequate bonding strength.

PMID- 23112930
TI  - Comparison of three different orthodontic wires for bonded lingual retainer
      fabrication.
AB  - OBJECTIVE: We evaluated the detachment force, amount of deformation, fracture
      mode, and pull-out force of 3 different wires used for bonded lingual retainer
      fabrication. METHODS: We tested 0.0215-inch five-stranded wire (PentaOne, Masel;
      group I), 0.016 * 0.022-inch dead-soft eight-braided wire (Bond-A-Braid,
      Reliance; group II), and 0.0195-inch dead-soft coaxial wire (Respond, Ormco;
      group III). To test detachment force, deformation, and fracture mode, we embedded
      94 lower incisor teeth in acrylic blocks in pairs. Retainer wires were bonded to
      the teeth and vertically directed force was applied to the wire. To test pull-out
      force, wires were embedded in composite that was placed in a hole at the center
      of an acrylic block. Tensile force was applied along the long axis of the wire.
      RESULTS: Detachment force and mode of fracture were not different between groups.
      Deformation was significantly higher in groups II and III than in group I (p <
      0.001). Mean pull-out force was significantly higher for group I compared to
      groups II and III (p < 0.001). CONCLUSIONS: Detachment force and fracture mode
      were similar for all wires, but greater deformations were seen in dead-soft
      wires. Wire pull-out force was significantly higher for five-stranded coaxial
      wire than for the other wires tested. Five-stranded coaxial wires are suggested
      for use in bonded lingual retainers.

PMID- 23112931
TI  - Comparison of arch form between ethnic Malays and Malaysian Aborigines in
      Peninsular Malaysia.
AB  - OBJECTIVE: To determine and compare the frequency distribution of various arch
      shapes in ethnic Malays and Malaysian Aborigines in Peninsular Malaysia and to
      investigate the morphological differences of arch form between these two ethnic
      groups. METHODS: We examined 120 ethnic Malay study models (60 maxillary, 60
      mandibular) and 129 Malaysian Aboriginal study models (66 maxillary, 63
      mandibular). We marked 18 buccal tips and incisor line angles on each model, and
      digitized them using 2-dimensional coordinate system. Dental arches were
      classified as square, ovoid, or tapered by printing the scanned images and
      superimposing Orthoform arch templates on them. RESULTS: The most common
      maxillary arch shape in both ethnic groups was ovoid, as was the most common
      mandibular arch shape among ethnic Malay females. The rarest arch shape was
      square. Chi-square tests, indicated that only the distribution of the mandibular
      arch shape was significantly different between groups (p = 0.040). However, when
      compared using independent t-tests, there was no difference in the mean value of
      arch width between groups. Arch shape distribution was not different between
      genders of either ethnic group, except for the mandibular arch of ethnic Malays.
      CONCLUSIONS: Ethnic Malays and Malaysian Aborigines have similar dental arch
      dimensions and shapes.

PMID- 23112932
TI  - Reader's Forum.

PMID- 23112933
TI  - Three-dimensional soft tissue analysis for the evaluation of facial asymmetry in
      normal occlusion individuals.
AB  - OBJECTIVE: To identify the right and left difference of the facial soft tissue
      landmarks three-dimensionally from the subjects of normal occlusion individuals.
      MATERIALS AND METHODS: Cone-beam computed tomography (CT) scans were obtained in
      48 normal occlusion adults (24 men, 24 women), and reconstructed into 3
      dimensional (3D) models by using a 3D image soft ware. 3D position of 27 soft
      tissue landmarks, 9 midline and 9 pairs of bilateral landmarks, were identified
      in 3D coordination system, and their right and left differences were calculated
      and analyzed. RESULTS: The right and left difference values derived from the
      study ranged from 0.6 to 4.6 mm indicating a high variability according to the
      landmarks. In general, the values showed a tendency to increase according to the
      lower and lateral positioning of the landmarks in the face. Overall differences
      were determined not only by transverse differences but also by sagittal and
      vertical differences, indicating that 3D evaluation would be essential in the
      facial soft tissue analysis. CONCLUSIONS: Means and standard deviations of the
      right and left difference of facial soft tissue landmarks derived from this study
      can be used as the diagnostic standard values for the evaluation of facial
      asymmetry.

PMID- 23112934
TI  - Response of masticatory muscles to passive stretch stimulus - from perspectives
      of functional appliances.
AB  - OBJECTIVE: The aims of this study were to examine whether a passive stretch
      stimulus by means of a functional appliance induces changes in the fiber
      composition of masticatory muscles and whether these changes are similar to the
      changes in stretched limb muscle fibers by using RT-PCR, western blot, and
      immunohistochemical assays. METHODS: Five male New Zealand White rabbits were
      fitted with a prefabricated inclined plane on the maxillary central incisors to
      force the mandible forward (- 2 mm) and downward (- 4 mm). Further, 1 hind limb
      was extended and constrained with a cast so that the extensor digitorum longus
      (EDL) was stretched when the animal used the limb. The animals were sacrificed
      after 1 week and the masseter, lateral pterygoid, and EDL were processed and
      compared with those from control animals (n = 3). RESULTS: The stretched EDL had
      a significantly higher percentage of slow fibers, whereas the stretched
      masticatory muscles did not show changes in the composition of the major
      contractile proteins after 7 days. CONCLUSIONS: The transition of fiber
      phenotypes in response to a stretch stimulus may take longer in the masticatory
      muscles than in the limb muscles.

PMID- 23112935
TI  - Maxillary expansion with the memory screw: a preliminary investigation.
AB  - OBJECTIVE: The purpose of this study was to investigate the effects of a newly
      developed rapid maxillary expansion screw-the memory screw-over 6 months.
      METHODS: Five subjects, aged between 11.7 and 13.75 years, were enrolled in this
      study. All subjects underwent placement of a maxillary expansion appliance
      containing superelastic nickel-titanium open-coil springs in its screw bed. The
      parents of the patients and/or the patients themselves were instructed to
      activate the expansion screw by 2 quarter-turns 3 times a day (morning, midday,
      and evening; 6 quarter-turns a day). The mean expansion period was 7.52 +/- 1.04
      days. Dentoskeletal effects of the procedure, including dentoalveolar
      inclination, were evaluated. Measurements of all the parameters were repeated
      after 6 months of retention in order to check for relapse. RESULTS: Sella-Nasion
      A point (SNA) and Sella-Nasion/Gonion-Menton angles increased, and Sella-Nasion-B
      point (SNB) angle decreased in all the subjects during the expansion phase.
      However, they approximated to the initial values at the end of 6 months. On the
      other hand, the increments in maxillary apical base (Mxr-Mxl) and intermolar
      widths was quite stable. As expected, some amount of dentoalveolar tipping was
      observed. CONCLUSIONS: The newly developed memory expansion screw offers
      advantages of both rapid and slow expansion procedures. It widens the midpalatal
      suture and expands the maxilla with relatively lighter forces and within a short
      time. In addition, the resultant increments in the maxillary apical base and
      intermolar width remained quite stable even after 6 months of retention.

PMID- 23112936
TI  - Age, extraction rate and jaw surgery rate in Korean orthodontic clinics and small
      dental hospitals.
AB  - OBJECTIVE: This study aimed to investigate the current data regarding age, sex,
      and Angle Classification of Korean orthodontic patients and influence of these
      factors on the tendency to undergo extraction and orthognathic surgery. METHODS:
      The recent trends of Korean orthodontic patients were assessed using
      questionnaire survey. The questionnaires were e-mailed to orthodontists who met
      the study criteria; 58% of the orthodontists opened the e-mails, and 27.7%
      replied to the e-mails. In all, the medical records of 11,340 patients who
      underwent orthodontic treatment at private clinics and small dental hospitals in
      Korea were analyzed. RESULTS: The percentage of female patients in the study
      sample was 69.6%, and the average age of the patients was 19.87 years. The
      percentage of patients who were older than 19 years was 50.2%. Class II and Class
      III malocclusions were noted in 33.6% and 23.6% of patients, respectively.
      Extraction and orthognathic surgery were performed in 60.4% and 6.9% of patients,
      respectively. CONCLUSIONS: The results showed that there were a high percentage
      of adult, Class II malocclusion and extraction patients in private practices and
      small dental hospitals during the study period. Further, a relatively high
      proportion of adult patients opted to undergo orthognathic surgery.

PMID- 23112937
TI  - The effect of silver ion-releasing elastomers on mutans streptococci in dental
      plaque.
AB  - OBJECTIVE: The purpose of this study was to investigate the antimicrobial effect
      of silverized elastomers on mutans streptococci in dental plaque. METHODS: Forty
      patients undergoing orthodontic treatment were randomly placed into 1 of 2
      groups. We examined the maxillary right and left central incisors and premolars,
      and the mandibular right and left canines of all participants. We ligated the
      right maxillary and left mandibular teeth of the participants in group 1 with
      silverized elastomers and ligated their contralateral teeth with conventional
      elastomers. We ligated the left maxillary teeth and right mandibular teeth of
      group 2 participants with silverized elastomers. Each participant visited the
      clinic 4 times at 3-week intervals. We applied the elastomers to the teeth on one
      side of each patient's mouth during their first visit. During the second visit,
      the elastomers were removed for microbiological analysis and replaced with steel
      ligatures. During the third visit, we used silverized elastomers to ligate the
      teeth contralateral to those treated on the first visit. The elastomers were
      removed during the fourth visit, and microbiological analyses were performed. We
      compared the quantity of bacteria on silverized and conventional elastomers at
      the 0.05 level of significance. RESULTS: The percentage of mutans streptococci
      was not significantly different in cultures of dental plaque from the silverized
      and the conventional elastomers (p > 0.05). CONCLUSIONS: There was no significant
      difference between the antimicrobial effect of the silverized elastomers and that
      of the conventional elastomers.

PMID- 23112939
TI  - Reader's Forum.

PMID- 23112938
TI  - Late development of a mandibular second premolar.
AB  - In this report, we present the case of a girl with delayed odontogenesis of a
      lower second premolar for which she was followed up for 8.5 years. Congenital
      absence of permanent mandibular second premolars was observed at the initial
      radiographic examination at 8 years and 1 month. One year later, during the
      treatment period, an unexpected odontogenesis of a right second premolar was
      diagnosed on follow-up radiography. The original treatment plan was revised and a
      new plan was successfully implemented. Th is unusual case showed that the
      orthodontist's clinical philosophy must be flexible because unexpected situations
      can arise, especially when treating growing patients.

PMID- 23112940
TI  - Preliminary study of Korean orthodontic residents' current concepts and knowledge
      of cleft lip and palate management.
AB  - OBJECTIVE: A national survey was conducted to assess orthodontic residents'
      current concepts and knowledge of cleft lip and palate (CLP) management in Korea.
      METHODS: A questionnaire consisting of 7 categories and 36 question items was
      distributed to 16 senior chief residents of orthodontic department at 11 dental
      university hospitals and 5 medical university hospitals in Korea. All respondents
      completed the questionnaires and returned them. RESULTS: All of the respondents
      reported that they belonged to an interdisciplinary team. Nineteen percent
      indicated that they use presurgical infant orthopedic (PSIO) appliances. The
      percentage of respondents who reported they were 'unsure' about the methods about
      for cleft repair operation method was relatively high. Eighty-six percent
      reported that the orthodontic treatment was started at the deciduous or mixed
      dentition. Various answers were given regarding the amount of maxillary expansion
      for alveolar bone graft and the estimates of spontaneous or forced eruption of
      the upper canine. Sixty-seven percent reported use of a rapid maxillary expansion
      appliance as an anchorage device for maxillary protraction with a facemask. There
      was consensus among respondents regarding daily wearing time, duration of
      treatment, and amount of orthopedic force. Various estimates were given for the
      relapse percentage after maxillary advancement distraction osteogenesis (MADO).
      Most respondents did not have sufficient experience with MADO. CONCLUSIONS: These
      findings suggest that education about the concepts and methods of PSIO and
      surgical repair, consensus regarding orthodontic management protocols, and
      additional MADO experience are needed in order to improve the quality of CLP
      management in Korean orthodontic residents.

PMID- 23112941
TI  - Evaluation of mandibular cortical bone thickness for placement of temporary
      anchorage devices (TADs).
AB  - OBJECTIVE: In this study, we measured the cortical bone thickness in the
      mandibular buccal and lingual areas using computed tomography in order to
      evaluate the suitability of these areas for application of temporary anchorage
      devices (TADs) and to suggest a clinical guide for TADs. METHODS: The buccal and
      lingual cortical bone thickness was measured in 15 men and 15 women. Bone
      thickness was measured 4 mm apical to the interdental cementoenamel junction
      between the mandibular canine and the 2nd molar using the transaxial slices in
      computed tomography images. RESULTS: The cortical bone in the mandibular buccal
      and lingual areas was thicker in men than in women. In men, the mandibular
      lingual cortical bone was thicker than the buccal cortical bone, except between
      the 1st and 2nd molars on both sides. In women, the mandibular lingual cortical
      bone was thicker in all regions when compared to the buccal cortical bone. The
      mandibular buccal cortical bone thickness increased from the canine to the
      molars. The mandibular lingual cortical bone was thickest between the 1st and 2nd
      premolars, followed by the areas between the canine and 1st premolar, between the
      2nd premolar and 1st molar, and between the 1st molar and 2nd molar. CONCLUSIONS:
      There is sufficient cortical bone for TAD applications in the mandibular buccal
      and lingual areas. This provides the basis and guidelines for the clinical use of
      TADs in the mandibular buccal and lingual areas.

PMID- 23112942
TI  - Histopathologic investigation of the effects of prostaglandin E2 administered by
      different methods on tooth movement and bone metabolism.
AB  - OBJECTIVE: The aim of this study was to investigate and compare the in vivo
      effects of prostaglandin E2 (PGE2) administered by different methods on
      orthodontic tooth movement and bone metabolism macroscopically,
      histopatologically, and biochemically. METHODS: Forty-five young adult New
      Zealand rabbits were randomly divided into 3 experimental groups (n = 10/group),
      1 positive control group (n = 10), and 1 negative control group (n = 5). The
      experimental rabbits were fitted with springs exerting 20-g reciprocal force on
      the maxillary incisors and PGE2 (10 ug/mL) was administered by the intravenous,
      submucosal, or intraligamentous route after appliance insertion and on days 1, 3,
      7, and 14 thereafter. All rabbits were sacrificed on day 21 and their premaxillae
      were resected for histologic evaluation. RESULTS: Tooth movement was observed in
      the experimental and positive control groups, but the intraligamentous PGE2 group
      had the highest values of all analyzed parameters, including serum calcium and
      phosphorus levels and osteoclastic and osteoblastic populations (p < 0.001).
      CONCLUSIONS: Submucosal and intraligamentous PGE2 administration significantly
      increases orthodontic tooth movement and bone metabolism, but the
      intraligamentous route seems to be more effective.

PMID- 23112943
TI  - Variations in surface roughness of seven orthodontic archwires: an SEM
      profilometry study.
AB  - OBJECTIVE: The purpose of this study was to evaluate the surface roughness (SR)
      of 2 types of orthodontic archwires made by 4 different manufacturers. METHODS:
      This in vitro experimental study was conducted on 35 specimens of 7 different
      orthodontic archwires, namely, 1 nickel-titanium (NiTi) archwire each from the
      manufacturers American Orthodontics, OrthoTechnology, All-Star Orthodontics, and
      Smart Technology, and 1 stainless steel (SS) archwire each from the manufacturers
      American Orthodontics, OrthoTechnology, and All-Star Orthodontics. After
      analyzing the composition of each wire by energy-dispersive X-ray analysis, the
      SR of each wire was determined by scanning electron microscopy (SEM) and surface
      profilometry. Data were analyzed using the Kruskal-Wallis and Mann-Whitney U
      tests (alpha < 0.05). RESULTS: The average SR of NiTi wires manufactured by Smart
      Technology, American Orthodontics, OrthoTechnology, and All-Star Orthodontics
      were 1,289 +/- 915 A degrees , 1,378 +/- 372 A degrees , 2,444 +/- 369 A degrees
      , and 5,242 +/- 2,832 A degrees , respectively. The average SR of SS wires
      manufactured by All-Star Orthodontics, OrthoTechnology, and American Orthodontics
      were 710 +/- 210 A degrees , 1,831 +/- 1,156 A degrees , and 4,018 +/- 2,214 A
      degrees , respectively. Similar to the results of profilometry, the SEM images
      showed more defects and cracks on the SS wire made by American Orthodontics and
      the NiTi wire made by All-Star Orthodontics than others. CONCLUSIONS: The NiTi
      wire manufactured by All-Star Orthodontics and the SS wire made by American
      Orthodontics were the roughest wires.

PMID- 23112944
TI  - Effect of fangchinoline on root resorption during rat orthodontic tooth movement.
AB  - OBJECTIVE: To evaluate the short-term effect of fangchinoline, an
      antiinflammatory drug widely used in Asia, on root resorption that is associated
      with orthodontic tooth movement. METHODS: Twenty-four Wistar rats were randomly
      divided into 6 groups. Mesial forces of 0, 50, or 100 g were applied to the
      maxillary first molar of the rats in each group for 14 days by activating nickel
      titanium closed-coil springs. One-half of the rats receiving each of these
      treatments also received injections of 200 uL fangchinoline every 2 days.
      Finally, movement of the maxillary first molars was measured using digitized
      radiographs. The molars were extracted and the surfaces of the root resorption
      craters were recorded using a scanning electron microscope. The distance the
      molars moved and resorptionarea ratio was measured, and results were analyzed
      using 2-way ANOVA tests. RESULTS: There were no statistical differences in the
      distances the first molars moved under 50 or 100 g force, regardless of treatment
      with fangchinoline. However, the resorption area ratios were significantly
      smaller in those rats that were treated with both tension and fangchinoline than
      in those rats treated by tension alone. CONCLUSIONS: Fangchinoline reduced the
      resorption area ratio in rats and is therefore an important means of alleviating
      root resorption.

PMID- 23112945
TI  - Management of acquired open bite associated with temporomandibular joint
      osteoarthritis using miniscrew anchorage.
AB  - This article reports the orthodontic treatment of a patient with skeletal
      mandibular retrusion and an anterior open bite due to temporomandibular joint
      osteoarthritis (TMJ-OA) using miniscrew anchorage. A 46-year-old woman had a
      Class II malocclusion with a retropositioned mandible. Her overjet and overbite
      were 7.0 mm and -1.6 mm, respectively. She had limited mouth opening, TMJ sounds,
      and pain. Condylar resorption was observed in both TMJs. Her TMJ pain was reduced
      by splint therapy, and then orthodontic treatment was initiated. Titanium
      miniscrews were placed at the posterior maxilla to intrude the molars. After 2
      years and 7 months of orthodontic treatment, an acceptable occlusion was achieved
      without any recurrence of TMJ symptoms. The retropositioned mandible was
      considerably improved, and the lips showed less tension upon lip closure. The
      maxillary molars were intruded by 1.5 mm, and the mandible was subsequently
      rotated counterclockwise. Magnetic resonance imaging of both condyles after
      treatment showed avascular necrosis-like structures. During a 2-year retention
      period, an acceptable occlusion was maintained without recurrence of the open
      bite. In conclusion, correction of open bite and clockwise-rotated mandible
      through molar intrusion using titanium miniscrews is effective for the management
      of TMJ-OA with jaw deformity.

PMID- 23112946
TI  - Reader's Forum.

PMID- 23112947
TI  - Three-dimensional finite element analysis of the deformation of the human
      mandible: a preliminary study from the perspective of orthodontic mini-implant
      stability.
AB  - OBJECTIVE: The aims of this study were to investigate mandibular deformation
      under clenching and to estimate its effect on the stability of orthodontic mini
      implants (OMI). METHODS: Three finite element models were constructed using
      computed tomography (CT) images of 3 adults with different mandibular plane
      angles (A, low; B, average; and C, high). An OMI was placed between #45 and #46
      in each model. Mandibular deformation under premolar and molar clenching was
      simulated. Comparisons were made between peri-orthodontic mini-implant
      compressive strain (POMI-CSTN) under clenching and orthodontic traction forces
      (150 g and 200 g). RESULTS: Three models with different mandibular plane angles
      demonstrated different functional deformation characteristics. The compressive
      strains around the OMI were distributed mesiodistally rather than
      occlusogingivally. In model A, the maximum POMI-CSTN under clenching was observed
      at the mesial aspect of #46 (1,401.75 microstrain [uE]), and similar maximum POMI
      CSTN was observed under a traction force of 150 g (1,415 uE). CONCLUSIONS: The
      maximum POMI-CSTN developed by clenching failed to exceed the normally allowed
      compressive cortical bone strains; however, additional orthodontic traction force
      to the OMI may increase POMI-CSTN to compromise OMI stability.

PMID- 23112948
TI  - A method for mandibular dental arch superimposition using 3D cone beam CT and
      orthodontic 3D digital model.
AB  - OBJECTIVE: The purpose of this study was to develop superimposition method on the
      lower arch using 3-dimensional (3D) cone beam computed tomography (CBCT) images
      and orthodontic 3D digital modeling. METHODS: Integrated 3D CBCT images were
      acquired by substituting the dental portion of 3D CBCT images with precise dental
      images of an orthodontic 3D digital model. Images were acquired before and after
      treatment. For the superimposition, 2 superimposition methods were designed.
      Surface superimposition was based on the basal bone structure of the mandible by
      surface-to-surface matching (best-fit method). Plane superimposition was based on
      anatomical structures (mental and lingual foramen). For the evaluation, 10
      landmarks including teeth and anatomic structures were assigned, and 30 times of
      superimpositions and measurements were performed to determine the more
      reproducible and reliable method. RESULTS: All landmarks demonstrated that the
      surface superimposition method produced relatively more consistent coordinate
      values. The mean distances of measured landmarks values from the means were
      statistically significantly lower with the surface superimpositions method.
      CONCLUSIONS: Between the 2 superimposition methods designed for the evaluation of
      3D changes in the lower arch, surface superimposition was the simpler, more
      reproducible, reliable method.

PMID- 23112949
TI  - Differences in molar relationships and occlusal contact areas evaluated from the
      buccal and lingual aspects using 3-dimensional digital models.
AB  - OBJECTIVE: The aims of this study were to use a 3-dimensional (3D) system to
      compare molar relationship assessments performed from the buccal and lingual
      aspects, and to measure differences in occlusal contact areas between Class II
      and Class I molar relationships. METHODS: Study casts (232 pairs from 232
      subjects, yielding a total of 380 sides) were evaluated from both the buccal and
      lingual aspects, so that molar relationships could be classified according to the
      scheme devised by Liu and Melsen. Occlusal contact areas were quantified using 3D
      digital models, which were generated through surface scanning of the study casts.
      RESULTS: A cusp-to-central fossa relationship was observed from the lingual
      aspect in the majority of cases classified from the buccal aspect as Class I
      (89.6%) or mild Class II (86.7%). However, severe Class II cases had lingual cusp
      to-mesial triangular fossa or marginal ridge relationships. Mean occlusal contact
      areas were similar in the Class I and mild Class II groups, while the severe
      Class II group had significantly lower values than either of the other 2 groups
      (p < 0.05). CONCLUSIONS: Buccal and lingual assessments of molar relationships
      were not always consistent. Occlusal contact areas were lowest for the Class II
      severe group, which seems to have the worst molar relationships - especially as
      seen from the lingual aspect.

PMID- 23112950
TI  - Relationship between Class III malocclusion and hyoid bone displacement during
      swallowing: a cine-magnetic resonance imaging study.
AB  - OBJECTIVE: The displacement of the hyoid bone (HB) is a critical biomechanical
      component of the swallowing function. The aim of this study was to evaluate the
      swallowing-induced vertical and horizontal displacements of the HB in subjects
      with 2 different magnitudes of skeletal Class III malocclusion, by means of real
      time, balanced turbo-field-echo (B-TFE) cine-magnetic resonance imaging. METHODS:
      The study population comprised 19 patients with mild skeletal Class III
      malocclusion, 16 with severe skeletal Class III malocclusion, and 20 with a
      skeletal Class I relationship. Before the commencement of the study, all subjects
      underwent cephalometric analysis to identify the nature of skeletal
      malformations. B-TFE images were obtained for the 4 consecutive stages of
      deglutition as each patient swallowed 10 mL of water, and the vertical and
      horizontal displacements of the HB were measured at each stage. RESULTS: At all
      stages of swallowing, the vertical position of the HB in the severe Class III
      malocclusion group was significantly lower than those in the mild Class III and
      Class I malocclusion groups. Similarly, the horizontal displacement of the HB was
      found to be significantly associated with the severity of malocclusion, i.e., the
      degree of Class III malocclusion, while the amount of anterior displacement of
      the HB decreased with an increase in the severity of the Class III deformity.
      CONCLUSIONS: Our findings indicate the existence of a relationship between the
      magnitude of Class III malocclusion and HB displacement during swallowing.

PMID- 23112951
TI  - Evaluation of anxiety level changes during the first three months of orthodontic
      treatment.
AB  - OBJECTIVE: To determine the changes in dental anxiety, state anxiety, and trait
      anxiety levels of patients and their parents after 3 months of active orthodontic
      treatment. METHODS: We evaluated 120 patients and one parent of each patient.
      State Anxiety (STAI-S), Trait Anxiety (STAI-T), and Corah's Dental Anxiety Scale
      (DAS) were administered before orthodontic treatment (T1) and after 3 months of
      treatment (T2). Differences in scores between T1 and T2 were compared using
      paired-sample t-tests and the relationship between the scores of the DAS and the
      STAI were analyzed using a bivariate two-tailed Pearson correlation test.
      RESULTS: Dental anxiety and state anxiety levels decreased among the patients
      after adjustment to orthodontic treatment (p < 0.001). However, 3 months of
      treatment was not sufficient to decrease the anxiety levels of parents (p >
      0.05). Patient trait anxiety affected patient state anxiety and dental anxiety (p
      < 0.01). Additionally, a significant correlation was found between patient dental
      anxiety and parent dental anxiety (p < 0.05). CONCLUSIONS: Dental anxiety and
      state anxiety levels decrease after patients become familiar with their
      orthodontist and they became accustomed to orthodontic treatment. However, 3
      months is not a sufficient length of time to decrease parental anxiety levels.

PMID- 23112952
TI  - Histologic effects of intentional-socket-assisted orthodontic movement in
      rabbits.
AB  - OBJECTIVE: This study aimed to evaluate the effect of an intentionally created
      socket on bone remodeling with orthodontic tooth movement in rabbits. METHODS:
      Eighteen male rabbits weighing 3.8 - 4.25 kg were used. An 8-mm deep and 2-mm
      wide socket was drilled in the bone 1 mm mesial to the right mandibular first
      premolar. The left first premolar was extracted to serve as an extraction socket.
      A traction force of 100 cN was applied to the right first premolar and left
      second premolar. Sections were obtained at the middle third of the moving tooth
      for both the drilled and extraction sockets and evaluated with hematoxylin and
      eosin staining and immunohistochemical analyses. The amount of tooth movement and
      tartrate-resistant acid phosphatase (TRAP)-positive cell count were compared
      between the 2 groups using the Mann-Whitney U test. RESULTS: At week 2, the
      distance of tooth movement was significantly higher in the intentional socket
      group (p < 0.05) than in the extraction socket group. The number of TRAP-positive
      cells decreased in week 2 but increased in week 3 (p < 0.05). However, there were
      no significant differences between the groups. Furthermore, results of
      transforming growth factor (TGF)-beta staining revealed no significant
      differences. CONCLUSIONS: The intentional socket group showed greater distance of
      tooth movement than did the extraction socket group at week 2. Osteoclast counts
      and results of immunohistochemical analyses suggested elevated bone remodeling in
      both the groups. Thus, osteotomy may be an effective modality for enhancing tooth
      movement in orthodontic treatment.

PMID- 23112953
TI  - In vitro evaluation of resistance to sliding in self-ligating and conventional
      bracket systems during dental alignment.
AB  - OBJECTIVE: To investigate the resistance to sliding (RS) in self-ligating and
      conventional ligation bracket systems at 5 different second-order bracket
      angulations by using low-stiffness alignment wires in a 3-bracket experimental
      model and to verify the performance of the main RS components in both systems
      when these wires are used. METHODS: Interactive self-ligating brackets with
      closed and open slides were used for the self-ligating (SL) and conventional
      ligation (CL) groups, respectively; elastomeric ligatures (1 mm inner diameter)
      were used in the latter system. The alignment wire used was 0.014 inch heat
      activated NiTi (austenitic finish temperature set at 36C by the manufacturer). A
      custom-made testing machine was used to measure frictional resistance. Tests were
      repeated 5 times at every angulation simulated. All data were analyzed
      statistically. RESULTS: The RS increased significantly with increasing angulation
      in both SL and CL groups (p < 0.0001). However, the RS values were significantly
      higher at every angulation (p < 0.0001) in the CL group. CONCLUSIONS: Despite the
      relevance of the binding phenomenon, ligation forces predominantly affect the RS
      when low-stiffness alignment wires are used.

PMID- 23112954
TI  - Assessment of gamma-H2AX levels in circulating tumor cells from patients
      receiving chemotherapy.
AB  - Circulating tumor cells (CTCs) are prognostic markers in a variety of solid tumor
      malignancies. The potential of CTCs to be used as a "liquid biopsy" to monitor a
      patient's condition and predict drug response and resistance is currently under
      investigation. Using a negative depletion, enrichment methodology, CTCs isolated
      from the peripheral blood of breast cancer patients with stage IV breast cancer
      undergoing DNA damaging therapy with platinum-based therapy were enriched. The
      enriched cell suspensions were stained with an optimized labeling protocol
      targeting: nuclei, cytokeratins 8, 18, and 19, the surface marker CD45, and the
      presence of the protein gamma-H2AX. As a direct or indirect result of platinum
      therapy, double-strand break of DNA initiates phosphorylation of the histone
      H2AX, at serine 139; this phosphorylated form is referred to as gamma-H2AX. In
      addition to gamma-H2AX staining in specific locations with the cell nuclei,
      consistent with previous reports and referred to as foci, more general staining
      in the cell cytoplasm was also observed in some cells suggesting the potential of
      cell apoptosis. Our study underscores the utility and the complexity of
      investigating CTCs as predictive markers of response to various therapies.
      Additional studies are ongoing to evaluate the diverse gamma-H2AX staining
      patterns we report here which needs to be further correlated with patient
      outcomes.

PMID- 23112955
TI  - Anti-idiotype antibodies in cancer treatment: the pharmaceutical industry
      perspective.
AB  - Active immunotherapy is an interesting field from the industry's perspective and
      in the last years, regulatory agencies and the medical community have showed
      renewed expectations and interest in cancer vaccines. The development of new
      immune therapies offers many challenges, and this is reflected in the small
      number of phase III trials showing clear benefits. Traditional concepts applied
      in clinical trials for the development of chemotherapeutic agents may be
      inadequate for immunotherapies and a new paradigm is emerging. It is possible
      that organized efforts and funding will accelerate the development of
      therapeutically effective cancer vaccines. This article reviews the attributes of
      cancer vaccines which make them attractive from the industry's perspective, and
      focuses especially in the characteristics of Racotumomab, an anti-idiotype
      antibody vaccine.

PMID- 23112956
TI  - Recombinant heat shock protein 70 in combination with radiotherapy as a source of
      tumor antigens to improve dendritic cell immunotherapy.
AB  - Local radiotherapy (RT) plus intratumoral dendritic cell (DC) injection can
      mediate immunological response. We hypothesized that co-injection of exogenous
      recombinant heat shock protein 70 (rHsp70) in combination with RT-DC could be as
      effective as co-injection of HSP-peptide for evoking specific immune response.
      rHsp70-prostate-specific antigen (rHSP70C'-PSA) and alpha-fetoprotein (rHSP70C'
      AFP) were used to compare specific response. Growth inhibition of the tumor and
      the systemic anti-tumor immune response were measured on CT26/PSA and CT26/AFP
      mice model. Intratumoral co-injection of rHsp70 and DC into the irradiated tumor
      site induced a more potent anti-tumor immune response than injection of DC alone.
      rHsp70 was as effective as rHsp70C'-PSA or rHsp70C'-AFP in inducing a tumor
      specific cytotoxic T lymphocyte response or tumor growth delay. These results
      demonstrate that co-administration with rHsp70 and RT could be a simple and
      effective source of tumor antigens to achieve RT-DC immunotherapy protocol and
      easy to apply in clinical use.

PMID- 23112957
TI  - Maintenance treatment with chemotherapy and immunotherapy in non-small cell lung
      cancer: a case report.
AB  - A 53-years-old woman was diagnosed with lung adenocarcinoma state IV (synchronous
      pleural involvement) in April 2009. First-line systemic treatment included six
      cycles of Carboplatin, Paclitaxel, and Bevacizumab. Partial response was
      achieved. Maintenance therapy with Bevacizumab and Pemetrexed was given from
      September 2009 to February 2010. No response changes were observed. Immunotherapy
      was initiated, and then Pemetrexed was given with the same disease status. Both
      treatments were well tolerated. Immunotherapy toxicity included reaction at the
      site of injection grade 2. At present, the patient is still on this treatment.
      Given the poor prognosis of patients with advanced lung cancer, the combination
      of both treatments during the stable phase of the disease may improve progression
      free survival.

PMID- 23112958
TI  - Radiation as an immunological adjuvant: current evidence on dose and
      fractionation.
AB  - Ionizing radiation to a cancer site has the ability to convert the irradiated
      tumor in an immunogenic hub. However, radiation is a complex modifier of the
      tumor microenvironment and, by itself, is seldom sufficient to induce a
      therapeutically significant anti-tumor immune response, since it can also
      activate immune suppressive pathways. While several combinations of local
      radiation and immunotherapy have been shown in pre-clinical models to induce
      powerful anti-tumor immunity, the optimal strategy to achieve this effect remains
      to be defined. When used in vivo, radiation effects on tumors depend on the dose
      per fraction applied, the number of fractions used, and the total dose. Moreover,
      the interplay of these three variables is contingent upon the tumor setting
      studied, both in pre-clinical and clinical applications. To enable repair of the
      collateral damage to the normal tissue, radiation is usually given in multiple
      fractions, usually of 2 Gy. Generally, the use of larger fractions is limited to
      stereotactic applications, whereby optimal immobilization reduces inter- and
      intrafraction movement and permits a very conformal delivery of dose to the
      target, with optimal exclusion of normal tissue. Translation of the partnership
      of radiation and immunotherapy to the clinic requires a careful consideration of
      the radiation regimens used. To date, little is known on whether different
      dose/fractionation regimens have a specific impact on the anti-tumor immune
      response. Most experiments combining the two modalities were conducted with
      single fractions of radiotherapy. However, there is at least some evidencethat
      when combined with some specific immunotherapy approaches, the ability of
      radiation to promote anti-tumor immunity is dependent on the dose and
      fractionation employed. We critically review the available in vitro and in vivo
      data on this subject and discuss the potential impact of fractionation on the
      ability of radiation to synergize with immunotherapy.

PMID- 23112960
TI  - Novel approaches to develop Rift Valley fever vaccines.
AB  - Rift Valley fever (RVF) is endemic to sub-Saharan Africa, and has spread into
      Madagascar, Egypt, Saudi Arabia, and Yemen. Rift Valley fever virus (RVFV) of the
      family Bunyaviridae, genus Phlebovirus causes hemorrhagic fever, neurological
      disorders or blindness in humans, and high rate abortion and fetal malformation
      in ruminants. RVFV is classified as a Category A Priority pathogen and overlap
      select agent by CDC/USDA due to its potential impact on public health and
      agriculture. There is a gap in the safety and immunogenicity in traditional RVF
      vaccines; the formalin-inactivated RVFV vaccine TSI-GSD-200 requires three doses
      for protection, and the live-attenuated Smithburn vaccine has a risk to cause
      abortion and fetal malformation in pregnant ruminants. In this review, problems
      of traditional vaccines and the safety and efficacy of recently reported novel
      RVF candidate vaccines including subunit vaccines, virus vector, and replicons
      are discussed.

PMID- 23112961
TI  - Causative role of gut microbiota in non-alcoholic fatty liver disease
      pathogenesis.

PMID- 23112959
TI  - The role of innate immune signals in immunity to Brucella abortus.
AB  - Innate immunity serves as the first line of defense against infectious agents
      such as intracellular bacteria. The innate immune platform includes Toll-like
      receptors (TLRs), retinoid acid-inducible gene-I-like receptors and other
      cytosolic nucleic acid sensors, nucleotide-binding and oligomerization domain
      like receptors, adaptors, kinases and other signaling molecules that are required
      to elicit effective responses against different pathogens. Our research group has
      been using the Gram-negative bacteria Brucella abortus as a model of pathogen. We
      have demonstrated that B. abortus triggers MAPK and NF-kappaB signaling pathways
      in macrophages in a MyD88 and IRAK-4-dependent manner. Furthermore, we claimed
      that so far TLR9 is the most important single TLR during Brucella infection. The
      identification of host receptors that recognize pathogen-derived nucleic acids
      has revealed an essential role for nucleic acid sensing in the triggering of
      immunity to intracellular pathogens. Besides TLRs, herein we describe recent
      advances in NOD1, NOD2, and type I IFN receptors in innate immune pathways during
      B. abortus infection.

PMID- 23112962
TI  - Molecular biology of gallbladder cancer: potential clinical implications.
AB  - Gallbladder cancer (GBC) is a common malignancy of the biliary tract and involves
      the changes in multiple oncogenes and multiple genetic genes. Since over the past
      decade there has been an advance in the knowledge of the genetic basis of cancer,
      mainly as a result of the rapid progression of molecular technology; however,
      conventional therapeutic approaches have not had much impact on the course of
      this aggressive neoplasm. Knowledge of the molecular biology of GBC is rapidly
      growing. Genetic alterations in GBC include adenosine triphosphate-binding
      cassette transporter ABCG8, membrane-bound enzyme ADAM-17 of multi-functional
      gene family, and other genes including p53, COX2, XPC, and RASSF1A. The advances
      in molecular biology have potential implications for the detection of this
      disease, using Synuclein-gamma, Syndecan-1, glycoprotein 72 (TAG-72), tumor
      endothelial marker 8 protein (TEM8) and TNF-alpha. The use of these molecular
      diagnostic methods is of clinical importance for the gene replacement therapy,
      genetic prodrug activation therapy, and antisense immunology technology for the
      treatment of malignancy. The author reviewed recent publications on PubMed, and
      summarized molecular biology of GBC, with an emphasis on features of potential
      clinical implications for diagnosis and management.

PMID- 23112963
TI  - Physiological effects of yogic practices and transcendental meditation in health
      and disease.
AB  - Yoga is an ancient Indian way of life, which includes changes in mental attitude,
      diet, and the practice of specific techniques such as yoga asanas (postures),
      breathing practices (pranayamas), and meditation to attain the highest level of
      consciousness. Since a decade, there has been a surge in the research on yoga,
      but we do find very few reviews regarding yogic practices and transcendental
      meditation (TM) in health and disease. Keeping this in view, a Medline search was
      done to review relevant articles in English literature on evaluation of
      physiological effects of yogic practices and TM. Data were constructed; issues
      were reviewed and found that there were considerable health benefits, including
      improved cognition, respiration, reduced cardiovascular risk, body mass index,
      blood pressure, and diabetes. Yoga also influenced immunity and ameliorated joint
      disorders.

PMID- 23112964
TI  - Malarial hepatopathy and its outcome in India.
AB  - BACKGROUND: Jaundice in Plasmodium falciparum malaria is multifactorial and its
      incidence varies in different regions. It is important to assess the incidence
      and factors associated with malarial hepatopathy as well as its complications to
      understand the pattern of disease presentation in order to undertake appropriate
      interventional measures. There is a paucity of data with regard to malarial
      hepatopathy and its outcome at the global level. AIM: The study was conducted to
      assess the pattern, spectrum of biochemical parameters and complications of
      hepatopathy related to P. falciparum malaria. MATERIALS AND METHODS: A
      descriptive study was conducted in a tertiary care hospital attached to a
      government medical institution in Assam, India. Demographic details of the
      hundred patients with P. falciparum malaria, their clinical and biochemical
      parameters, complications and outcome were collected using a prestructured
      proforma. Data was compared using proportion and Chi Square test. RESULTS: The
      proportion of those with malarial hepatopathy was 38% and the incidence was more
      in males and younger age group. The degree of hyperbilirubinemia, complications
      that include renal failure, shock, acute respiratory distress syndrome,
      hypoglycemia and mortality were significantly more among patients with
      hepatopathy (P<0.05). CONCLUSION: Malarial hepatopathy is associated with a
      higher incidence of complications like renal failure, shock, acute respiratory
      distress syndrome and hypoglycemia. Further studies are required to elucidate the
      factors associated with malarial hepatopathy and to prevent the complications and
      mortality.

PMID- 23112965
TI  - Comparison of Size 2.5 i-gelTM with Proseal LMATM in Anaesthetised, Paralyzed
      Children Undergoing Elective Surgery.
AB  - BACKGROUND: The newest variation of i-gel is its pediatric version. This novel
      supraglottic airway device has the added advantage of a drain tube. In this
      study, we compared the effectiveness of size 2.5 i-gel with size 2.5 ProSeal LMA.
      AIMS: This study was designed to investigate the usefulness of the size 2.5 i-gel
      compared with the ProSeal laryngeal mask airway (PLMA) of the same size in
      anesthetized, paralyzed children. MATERIALS AND METHODS: Sixty ASA grade I - II
      patients undergoing elective surgery were included in this prospective study and
      were randomly assigned to the i-gel and PLMA groups (30 patients in each group).
      A size 2.5 supraglottic airway was inserted according to the assigned group. We
      assessed the ease of insertion, hemodynamic data, oropharyngeal sealing pressure,
      and postoperative complications. RESULTS: There were no differences in the
      demographic and hemodynamic data, success rates for the first attempt of
      insertion, or postoperative airway morbidity among the two groups. The airway
      leak pressure of the i-gel group (27.12 +/- 1.69 cm H(2)O) was significantly
      higher than that of the PLMA group (22.75 +/- 1.46 cm H(2)O). CONCLUSION:
      Hemodynamic parameters, ease of insertion and postoperative complications were
      comparable between the i-gel and PLMA, but the nairway sealing pressure was
      significantly higher in the i-gel group.

PMID- 23112966
TI  - Photogrammetric analysis of palpebral fissure dimensions and its position in
      malaysian South Indian ethnic adults by gender.
AB  - BACKGROUND: Anthropometric data describing the palpebral fissure and its position
      is available for various populations. Unfortunately there is no data available
      for Malaysian South Indian. AIM: The present study was undertaken to determine
      the normative values for Malaysian South Indian according to gender. MATERIALS
      AND METHODS: Anthropometric measurement was done on standardized photographs
      taken from 300 MSI aged 18-26 years. The parameters were measured using
      computerized software. RESULTS: Significant sexual difference was observed in all
      parameters except canthal index, which includes palpebral fissure width (male,
      30.9 mm; female, 29.62 mm), palpebral fissure height (male, 11.06 mm; female,
      11.48 mm), palpebral fissure inclination (male, 4.72 degrees ; female, 7.04
      degrees ), outercanthal distance (male, 97.15 mm; female, 91.78 mm),
      interpupillary distance (male, 68.09 mm; female, 63.6 mm), intercanthal distance
      (male, 34.1 mm; female, 32.77 mm), and canthal index (male, 35.22 mm; female,
      35.86+/-4.44 mm). CONCLUSIONS: Sexual dimorphism was found in all parameters.
      Comparison of our results with other studies revealed the variation and
      similarities in key parameters. Establishing normative values and understanding
      the facial morphology of different ethnic groups is important in designing the
      treatment planning for an aesthetic oculoplastic procedure.

PMID- 23112967
TI  - Prediction of Clinical Outcome in Acute Hemorrhagic Stroke from a Single CT Scan
      on Admission.
AB  - BACKGROUND: From a single CT scan in primary intracerebral hemorrhage (ICH),
      clinical outcome can be assessed on admission by using the CT scan parameters.
      AIMS: The study aims to find out how hematoma volume, location of stroke, midline
      shift, intraventricular extension of bleed and ventricle compression influence
      the clinical outcome in patients with acute ICH. MATERIALS AND METHODS: Non
      contrast CT scan was done on admission in hospital for every patient with acute
      hemorrhagic stroke and was analyzed accordingly. Clinical assessments were done
      in National Institute of Health Stroke Scale (NIHSS). Chi-square test and
      multiple logistic regression analysis were used for statistical analysis.
      RESULTS: Mean hematoma volume associated with death before 30 days is 33.16 cm(3)
      (P < 0.0001), with survived after 30 days is 15.45 cm(3) (P < 0.0001), with NIHSS
      score >=16 is 29.03 cm(3) (P < 0.0001) and with NIHSS score <16 is 13.69 cm(3) (P
      < 0.0001). Independent poor prognostic factors were hematoma volume > 30 cm(3)
      (OR = 27.857), brain stem hemorrhage (OR = 6.000), intraventricular extension of
      bleed from other location (OR = 7.846), presence of ventricular compression alone
      (OR = 2.700) and in combination with midline shift of >= 5 mm (OR = 2.124).
      CONCLUSIONS: From a single CT scan during hospital admission, mortality and
      morbidity in next 30 days can be predicted. A hematoma volume >30 cm(3), brain
      stem hematoma, intraventricular extension of bleed and ventricular compression
      along and with midline shift are associated with early mortality in ICH.

PMID- 23112968
TI  - Ocular pseudoexfoliation and cardiovascular disease: a national cross-section
      comparison study.
AB  - BACKGROUND: Pseudoexfoliation is a systemic disorder characterized by the
      deposition of extracellular matrix material. The microfibrillar material that
      gives rise to the condition is visible clinically in the anterior segment of the
      eye, and is also found in other tissues, including blood vessels, skin,
      gallbladder, kidneys, lungs, and heart. AIMS: The present study aims to determine
      whether ocular pseudoexfoliation is associated with selected cardiovascular
      diseases. MATERIALS AND METHODS: A cross-section comparison study was conducted
      with the help of the Veterans Health Administration databases, using the
      International Classification of Diseases, Ninth revision, Clinical Modification
      for pseudoexfoliation of lens capsule and pseudoexfoliation glaucoma. Selected
      cardiovascular diseases and risk factors for cardiovascular disease were
      identified using the appropriate medical codes. Patients with primary open-angle
      glaucoma, chronic sinusitis, and benign prostatic hyperplasia served as the
      comparison groups. A logistic regression model was used to control for age,
      gender, race, and major cardiovascular risk factors. RESULTS: There were 6,046
      case patients with pseudoexfoliation; approximately half were diagnosed with
      pseudoexfoliation glaucoma. Various stages of ischemic heart disease,
      cardiomyopathy, and aortic aneurysm were significantly associated with ocular
      pseudoexfoliation, after controlling for age, gender, race, and major
      cardiovascular risk factors. Associations, in general, were less demonstrable
      relative to the primary open-angle glaucoma comparison group. CONCLUSION:
      Associations of ocular pseudoexfoliation with cardiovascular diseases were
      generally fewer and less pronounced when compared to patients with primary open
      angle glaucoma. These results add to the results of earlier studies, which
      suggest that open-angle glaucoma itself might be a risk factor for certain
      cardiovascular disorders.

PMID- 23112969
TI  - Social Determinants and its Influence on the Prevalence of Morbidity among
      Adolescent Girls.
AB  - BACKGROUND: The adolescent girls are more vulnerable, particularly in developing
      countries including India, due to various adverse socio-cultural and economic
      reasons. Majority of the health problems affecting adolescent girls are
      preventable by promotion of hygienic practices through proper health education by
      the teachers. AIM: This study was designed to examine the various factors
      influencing the prevalence of morbidity among school-going adolescent girls of
      Lucknow district in north India. MATERIALS AND METHODS: A cross-sectional study
      was carried out in urban and rural schools of Lucknow district from 2008 to 2009.
      Multistage random sampling was used to select the requisite number of girls. A
      total of 847 adolescent girls between 10 and 19 years of age were interviewed,
      and information regarding their socio-demographic characteristics was collected
      and clinical examination was carried out. Statistical analyses were done using
      percentage and Chi-square test. RESULTS: Of 847 adolescent girls, around 64.8%
      were found to be sick at the time of the study. Significant association of
      morbidity was observed with caste, birth order, type of family, socioeconomic
      status (SES), living status with parents/guardian, and general personal hygiene
      (P<0.05). CONCLUSION: This study reveals a high prevalence of morbidity. A strong
      need exists for planning and programming intervention activities for health needs
      in the area.

PMID- 23112970
TI  - Molecular detection of pneumocystis jirovecii in patients with respiratory tract
      infections.
AB  - BACKGROUND: Pneumocystis jirovecii, formerly known as P. carinii, is an
      opportunistic fungus causing Pneumocystis carinii pneumonia especially in
      immunocompromised patients. AIM: The aim of this study was to detect P. jirovecii
      in sputum samples from patients suspected of having respiratory tract infections.
      MATERIALS AND METHODS: In this study, 230 acid fast bacilli negative sputum
      samples from 230 patients presenting with respiratory tract infections submitted
      to three teaching hospitals' medical microbiology laboratories in Osun and Oyo
      States, Nigeria for routine investigation were examined for P. jirovecii by
      microscopical and polymerase chain reaction methods. RESULTS: P. jirovecii cysts
      were observed in 15 (6.5%) samples and polymerase chain reaction was positive for
      29 (12.6%) samples out of 230 samples examined. It was observed that the
      detection of P. jirovecii was associated with age (P < 0.05) while there were no
      associations between diagnosis, sex, and prevalence of P. jirovecii (P > 0.05).
      Polymerase chain reaction was showed to be a better method for the detection of
      P. jirovecii based on the 51.7% sensitivity and 100% specificity of the
      microscopy. CONCLUSION: The study concluded that P. jirovecii is prevalent in
      patients with respiratory tract infections in hospitals from the southwestern
      part of Nigeria and should be included in diagnosis of these infections in this
      part of the world.

PMID- 23112971
TI  - Pneumocystis jirovecii Pneumonia in Africa: Impact and Implications of Highly
      Sensitive Diagnostic Technologies.

PMID- 23112972
TI  - Mobile radiofrequency does not interfere with antiarrhythmic drugs in patients
      with ischemic heart disease.

PMID- 23112973
TI  - Clinical and bacteriological aspects of pyoderma.

PMID- 23112974
TI  - Association Between Serum Gamma-glutamyl Transferase Level and Hypertension in
      Indian Adults: A Population Based Cross-Sectional Study.

PMID- 23112975
TI  - Phosphodiesterase-III Inhibitors Amrinone and Milrinone on Epilepsy and
      Cardiovascular Activities.

PMID- 23112976
TI  - Clinical correlates and outcome of shoshin beriberi.

PMID- 23112977
TI  - CD45/CD8 Myeloid Histioid Antigen and Plasma Cell Antibody Immune Response in a
      Case of Malignant Melanoma.
AB  - The immune response in metastatic melanoma is not well established and therefore
      is of particular interest to test for recruitment of immune cells to the tumor. A
      46-year-old Caucasian female was evaluated for an asymptomatic right forearm
      mass. The lesion had been present for at least 4 years and had become painful 4
      months ago. Biopsies for hematoxylin and eosin (H and E) staining, as well as
      immunohistochemical analysis were performed on the primary tumor and on sentinel
      lymph nodes. The H and E staining was consistent with metastatic melanoma.
      Positive staining was noted on the tumor cells with S-100, Mart-1/Melan A/CD63,
      PNL2, HMB45, and tyrosinase. Peritumoral and intratumoral inflammatory cells
      stained positive for CD8, CD45, PCNA, myeloid histoid antigen, antihuman plasma
      cell antibody, and focal BRCA1. The staining patterns of CD8/CD45, myeloid
      histoid antigen and plasma cell antibody on inflammatory cells around the
      melanoma cells suggest an unusual type of immune response.

PMID- 23112978
TI  - Multifocal epithelial hyperplasia.

PMID- 23112979
TI  - Spontaneous pregnancy and unexplained infertility: a gift with many whys.

PMID- 23112980
TI  - Factors associated with organ donation.

PMID- 23112981
TI  - Austrian syndrome and multiple myeloma: a fatal combination.

PMID- 23112982
TI  - Hydranencephaly: a rare cause of an enlarging head size in an infant.

PMID- 23112983
TI  - Molecular epizootiology of rodent leishmaniasis in a hyperendemic area of iran.
AB  - BACKGROUND: Zoonotic cutaneous leishmaniasis (ZCL) is an expanding disease and
      public health problem in Iran. In the current study, natural Leishmania infection
      rate and seasonal fluctuation of the infection in Rhombomys opimus population of
      a hyperendemic focus of ZCL in Iran was investigated. METHODS: The study was
      conducted from October 2006 to October 2008 in Esfahan Province, central part of
      Iran. An extensive sampling of rodents using Sherman traps was done in different
      seasons. Nested PCR assay was used for detection and identification of Leishmania
      species and the results were confirmed using PCR-RFLP. RESULTS: Leishmania
      infection rate was 58.6% (34 of 58) using nested PCR. 44.8% of the gerbils were
      infected only with L. turanica and 1.7% with L. gerbilli alone. A mixed natural
      infection with L. major and L. turanica was seen in 12.1% of the rodents. L.
      major infection alone was not seen in R. opimus population in the study area. The
      highest and lowest Leishmania infection rates were observed in fall and spring
      respectively. L. turanica infection was observed throughout the year whereas
      mixed infections with L. major and L. turanica was not seen in spring.
      CONCLUSION: It is concluded that in the study area, L. major, L. gerbilli and L.
      turanica circulate in the population of R. opimus. Leishmania major infection
      usually accompanied by L. turanica in naturally infected gerbils with the highest
      rate in fall. It is recommended that the role of L. turanica in the epidemiology
      and transmission of ZCL be revisited.

PMID- 23112984
TI  - Prevalence of Genes Encoding Bi-Component Leukocidins among Clinical Isolates of
      Methicillin Resistant Staphylococcus aureus.
AB  - BACKGROUND: Staphylococcus aureus has been recognized as a major human pathogen
      and is the major cause of nosocomial infections. Gamma-toxin, leukocidin and
      other bi-component toxins are a family of proteins encoded by the hlg and luk-PV,
      respectively. Panton-Valentine leukocidin (PVL) is an example of these toxins and
      causes leukocyte destruction and tissue necrosis. The aim of this study was to
      determine the prevalence of bi-component leukocidin in Methicillin Resistant
      Staphylococcus aureus (MRSA) isolates in staphylococcal infections. METHODS:
      Collectively, 143 isolates of S. aureus were obtained from Tehran University of
      Medical Sciences hospitals and confirmed with biochemical tests. Then polymerase
      chain reaction was used to detect luk-PV loci and luk-E/D. Coagulase gene was
      used as internal control. The antibiotic susceptibility patterns of isolates were
      determined using disk diffusion method. RESULTS: Out of 149 S. aureus isolates
      24.2% were luk-PV positive and 73.8% were luk-E/D positive. CONCLUSION: There was
      PVL positive MRSA isolates with high prevalence in evaluated hospitals. The
      diseases from these bacteria are with extensive necrosis, leucopenia and even
      death. We desire that, prevent from progress and death by diagnosis and right
      treatment.

PMID- 23112985
TI  - Effect of eicosapentaenoic Acid (EPA) and vitamin e on the blood levels of
      inflammatory markers, antioxidant enzymes, and lipid peroxidation in Iranian
      basketball players.
AB  - BACKGROUND: Exercise can change the release of numerous cytokines and modulate
      their receptor systems. Dietary omega-3 lipids may decrease the levels of
      inflammatory cytokines and prostaglandins (PGs). Therefore, in this study, we
      investigated the effects of exercise and eicosapentaenoic acid (EPA)
      supplementation, with or without vitamin E, on the blood levels of IL-2, TNF
      alpha, catalase, glutathione reductase, and MDA in male basketball players.
      METHODS: Thirty-four well-trained male basketball players were enrolled into the
      study. Venous blood samples were obtained from all subjects between 5:00 and 6:00
      p.m., after intensive endurance exercising for 2 hours, at the baseline and after
      intervention. Subjects received 2g EPA and/or 400 IU vitamin E or placebo depends
      on their groups for 6 weeks. RESULTS: There were significant fall (paired t-test)
      in TNF-alpha in group1(P< 0.05), and in MDA in group 3 (P<0.05), whereas there
      were significant increase in glutathione reductase in groups1 and 3 (P< 0.05),
      and in MDA in group2 (P< 0.05).There were significant differences (Tukey) in
      glutathione reductase between groups 2 and 3 (P< 0.05), and in IL-2 between
      groups 1 and other groups (P< 0.01), but there were no significant differences in
      MDA, CAT, and TNF-alpha, among groups after 6 week of intervention. CONCLUSION:
      Six weeks of EPA+vitamin E supplementation enhances the plasma levels of IL-2 and
      erythrocytes glutathione reductase, whereas it reduces TNF-alpha, and 6 weeks of
      EPA supplementation alone enhances only the serum level of MDA.

PMID- 23112986
TI  - Prevalence of GBV-C RNA in HIV infected individuals in Tehran, Iran.
AB  - BACKGROUND: GB virus C (GBV-C) is a flavivirus that was characterized in 1995.
      The prevalence of GBV-C RNA in HIV-infected subjects has not been previously
      studied in Iran and was therefore determined. METHODS: We have investigated serum
      samples of 80 patients from Imam Khomeini Hospital, Tehran, Iran, whose HIV
      infection was confirmed in our laboratory by Western-blotting. We used nested-PCR
      to detect GBV-C/HGV RNA in their sera. RESULTS: GBV-C/HGV RNA was detected in 15
      (18.8%) of 80 patients. There was no significant difference in GBV-C/HGV RNA
      prevalence between males and females, in different age groups and HIV viral loads
      groups. CONCLUSION: The prevalence of GBV-C RNA was high in HIV-infected
      patients. There was no association between GBV-C RNA prevalence and specific
      gender, age, and HIV viral loads groups.

PMID- 23112987
TI  - Women pose innocent victims of landmines in postwar iran.
AB  - BACKGROUND: Although in the last few years there has been an increasing attention
      to the problem of landmines, to date, the implications of women being victims of
      landmine has not been duly dealt with in the world including Iran, which is
      estimated to be the second most landmine infested country in the world. Still,
      provinces by the west border of Iran, 18 years after cessation of Iraq-Iran war
      suffer from the burden of vast areas, highly infested with landmines. This study
      aimed to provide a gender focused insight into landmine accidents in Iran
      METHODS: In this retrospective study, women with documented deaths or injuries
      due to landmine and/or unexploded ordnances (UXO) explosions as documented in
      their medical records between Jul 1988 (after ceasefire) and Feb 2003 were
      studied in 5 western provinces of Iran. Data was analyzed by SPSS for Windows
      Version 11. P value under 0.05 was considered statistically significant RESULTS:
      During the 14-year study period, 252 women from 5 western provinces of Iran were
      reported to have injuries or death due to landmine and UXOs. All of the victims
      were civilians and the majority of them (47.6%) had one or more amputations. Most
      of them were injured in the period between1994 and 1998. The majority of the
      patients were young. CONCLUSION: Women who should take care of themselves as well
      as their families are more prone to sufferings inflicted by landmines and UXO.

PMID- 23112988
TI  - In vivo efficacy of gum obtained pistacia atlantica in experimental treatment of
      cutaneous leishmaniasis.
AB  - BACKGROUND: Recent circumstantial evidences are suggesting that an increasing
      number of Iranian patients with cutaneous leishmaniasis are unresponsive to
      meglumine antimoniate (Glucantime(r)). Pistacia atlantica is native plant in Iran
      (central, western, and eastern regions). Gum obtained Pistacia atlantica has been
      reported to possess considerable in vitro antimicrobial activity. In this study,
      we aimed to investigate antileishmanial activity of P. atlantica. METHODS: Male
      BALB/c mice were inoculated subcutaneously 2*10(6)L. major Promastigotes
      (MHROM/IR/75/ER) at the base of tail in 2007. Mice were randomly divided into 3
      groups. in group 1 Glucantime(r) was administered to the BALB/c mice in regimen
      of 60 mg per kg of body weight for 28 days by intraperitoneal injections per day,
      in group 2 the gum of P. atlantica var. Kurdica were tested by rubbing of local
      lesions for 28 days, group 3 infected but non-treated. Comparisons of treated
      groups and untreated group were done by two-way analysis of variance (ANOVA) 
      RESULTS: Topically rubbing administration of gum obtained P. atlantica var.
      kurdica daily for 28 days like Glucantime(r) decreased skin lesion size in the
      BALB/c mice infected with L. major compared with that in the control (P< 0.01).
      Treatment BALB/c mice with gum obtained P. atlantica var. kurdica and
      Glucantime(r) causes decrease number of parasitologicaly positive mice (P< 0.05).
      CONCLUSION: Our results show that gum obtained P. atlantica var. kurdica can be
      used for controlling cutaneous leishmaniasis caused by L. major and inhibiting
      development of cutaneous leishmaniasis lesions.

PMID- 23112989
TI  - Iran Mortality and Measures of Risk: Rankings for Public policy.
AB  - BACKGROUND: This paper offers mortality risk rankings for Iranian mortality data.
      It extends methods to include mixed cohorts, tests changes in mortality risks,
      compares measures of risk and discusses public policy implications. METHODS: The
      methodology used in risk measures takes current practice and extends it to
      include variations in population dynamics. The specification is presented and
      compared with existing literature. RESULTS: Our findings confirm literature
      results in the re-ordering that takes place when different risk measures are
      used. In addition, we find there is consistency in risk rankings between 1999 and
      2000 records of Iranian mortality data. Thus, these risk measures are stable,
      robust across time and relay risk information consistently. CONCLUSIONS: There
      are considerable implications in adopting particular risk measures for public
      policy. However, given properties of risk measures discussed here, it is clear
      that policy makers can select relevant risk measures depending on their
      priorities.

PMID- 23112990
TI  - The effects of vitamins e and d supplementation on erythrocyte superoxide
      dismutase and catalase in atopic dermatitis.
AB  - BACKGROUND: Atopic dermatitis is a public health problem worldwide. Increment of
      reactive oxygen species (ROS) production may be one of the contributing factors
      of tissue damage in atopic dermatitis. The present study was designed to
      determine the effect of vitamins E and/or D on erythrocyte superoxide dismutase
      and catalase activities in patients with atopic dermatitis. METHODS: In a
      randomized, double blind, placebo controlled clinical trial 45 atopic dermatitis
      patients were divided into four groups. Each group received one of the following
      supplements for 60 days: group A (n=11) vitamins E and D placebos; group B (n=
      12) 1600 international unit (IU) vitamin D3 plus vitamin E placebo; group C
      (n=11) 600 IU synthetic all-rac-alpha tocopherol plus vitamin D placebo; group D
      (n=11) 1600 IU vitamin D3 plus 600 IU synthetic all-rac-alpha tocopherol.
      Erythrocyte superoxide dismutase (SOD) and catalase activities, serum 25 (OH) D,
      plasma alpha-tocopherol were determined. The data were analyzed by analysis of
      variance (ANOVA) and paired t-test. RESULTS: After 60 days vitamin D and E
      supplementation, erythrocyte SOD activities increased in groups B, C and D (P=
      0.002, P= 0.016 and P= 0.015, respectively). Erythrocyte catalase activities
      increased in groups B and D (P= 0.026 and P= 0.004, respectively). The increment
      of erythrocyte catalase activity was not significant in group C. There was a
      positive significant correlation between SOD activity and serum 25 (OH) D (r=
      0.378, P= 0.01). CONCLUSIONS: It is concluded that vitamin D is as potent as
      vitamin E in increasing the activities of erythrocyte SOD and catalase in atopic
      dermatitis patients.

PMID- 23112991
TI  - Role of ideas and ideologies in evidence-based health policy.
AB  - Policy making in health is largely thought to be driven by three 'I's namely
      ideas, interests and institutions. Recent years have seen a shift in approach
      with increasing reliance being placed on role of evidence for policy making. The
      present article ascertains the role of ideas and ideologies in shaping evidence
      which is used to aid in policy decisions. The article discusses different
      theories of research-policy interface and the relative freedom of research-based
      evidence from the influence of ideas. Examples from developed and developed
      countries are cited to illustrate the contentions made. The article highlights
      the complexity of the process of evidence-based policy making, in a world driven
      by existing political, social and cultural ideologies. Consideration of this
      knowledge is paramount where more efforts are being made to bridge the gap
      between the 'two worlds' of researchers and policy makers to make evidence-based
      policy as also for policy analysts.

PMID- 23112992
TI  - What do patients expect from their physicians?
AB  - BACKGROUND: To identify the most important expectations that patients have from
      their physicians. METHODS: We collected data from 199 hospitalized and 201
      ambulatory patients (response rates 88% and 93% respectively). We used random
      sampling for selection of hospitalized patients and systematic sampling for the
      ambulatory ones. The questionnaire consisted of 18 different expectation items
      categorized in 5 domains. The participants scored each item from 1 to 9 using a
      VAS scale and ranked domains based on their importance. We analyzed the data
      using univariate and regression analyses. RESULTS: Among the ambulatory patients,
      the mean+/-standard error of the most important expectations was as follows:
      competency (8.9+/-0.01), courteousness (8.8+/-0.04), consultation in case of need
      (8.8+/-0.4), clear explanation of the disease (8.8+/-0.05) and attentiveness
      (8.8+/-0.04). In hospitalized patients, the following items were the most
      important: competency (8.4+/-0.08), courteousness (8.4+/-0.09), availability of
      physician (8.4+/-0.09), consultation in case of need (8.2+/-0.11), setting
      following appointments (8.2+/-0.1), and disease follow-up (8.2+/-0.09). In both
      groups, the most important domain of expectations was "competency and quality of
      care" followed by "availability" in hospitalized and "giving information and
      patient autonomy" among ambulatory patients. CONCLUSIONS: Our findings are
      similar to what reported in the literature from other countries and cultures. In
      addition to physician expertise and knowledge, patients value giving information
      and efficient doctor-patient relationship.

PMID- 23112993
TI  - Expenditure to treat thalassaemia: an experience at a tertiary care hospital in
      India.
AB  - BACKGROUND: The medical and economic problem of thalassaemia are considered to be
      a vast public health problem in the thalassaemia belt countries, emphasizing more
      on prenatal diagnosis as the solution of the problem. METHODS: A cross-sectional
      descriptive study was conducted in the Institute of Haematology & Transfusion
      Medicine located in Medical College, Kolkata, India to assess the socio
      demographic profile, clinical presentation, expenditure for treatment of
      thalassaemia patients and awareness about cause and prevention of the disease.
      RESULTS: Thalassaemia patients attended the Govt. setting were mostly from lower
      socioeconomic status with low level of literacy. Annual expenditure for treatment
      of thalassaemia ranged from $ 108 to 432; depending on type of treatment with
      average cost per transfusion was $ 5.2+/-2.2. Average 18.5%+/-14.3 of the total
      annual income was spent on the treatment for thalassaemia. Average man days or
      school days lost for the patients was 29.87+/-18.5 and 19.07+/-12.7 for the
      accompanying persons. CONCLUSION: Blood transfusion and carrier screening
      facilities should be decentralized to decrease the expenditure for treatment and
      alleviate the harassment of the families. Folate and calcium tablets, hepatitis B
      vaccination can be made available at government setting free of cost.

PMID- 23112994
TI  - Preparative SDS-PAGE Electroelution for Rapid Purification of Alkyl Hydroperoxide
      Reductase from Helicobacter pylori.
AB  - BACKGROUND: Alkyl hydroperoxide reductase (AhpC) of Helicobacter pylori is
      considered as a diagnostic antigen. Therefore, this antigen can be used to detect
      H. pylori infection by stool immunoassays such as ELISA. The aim of this study
      was to simplify the AhpC protein purification procedures. METHODS: For whole cell
      protein extraction, the bacterial cells were ruptured by octly-beta-D
      glucopyranoside. The isolation and purification of AhpC protein were attempted by
      various techniques including ammonium sulfate precipitation, dialysis,
      preparative sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE)
      and electroelution. RESULTS: A simple method was used for protein purification
      AhpC protein. One-dimensional preparative gel electrophoresis allows a single and
      short purification step; the high resolution capacity of this technique leads to
      a high level of purity of the protein. Moreover, it avoids contamination by other
      non-specific proteins which often appear during protein purification by column
      chromatography. CONCLUSION: The present method is simple, rapid and makes it
      possible to preparate AhpC from H. pylori.

PMID- 23112995
TI  - Urinary Schistosomiasis around Oyan Reservoir, Nigeria: Twenty Years after the
      First Outbreak.
AB  - BACKGROUND: Oyan reservoir, South-West Nigeria was constructed in 1984 to
      generate electricity but has altered the existing physical, biological and socio
      economic environment of the people. This study, carried out between October 2006
      and March 2008, aimed at investigating the current status of Schistosoma
      haematobium infection around the reservoir. METHODS: Urine samples from 536
      participants in five communities were examined for haematuria using reagent
      strips and S. haematobium ova was detected using sedimentation by gravity method.
      The participants were drawn from Abule Tuntun (n= 115), Ibaro (n= 156), Imala Odo
      (n= 88), Imala (n= 103) and Apojula (n= 74) communitie. RESULTS: Prevalence rates
      by haematuria were (Abule Tuntun- 33.04%; Ibaro- 73.07%; Imala odo- 60.22%; Imala
      7.77%; Apojula - 39.19%) and by presence of parasite ova were (Abule Tuntun-
      39.13%; Ibaro- 83.97%; Imala Odo- 62.5%; Imala- 20.39%; Apojula- 54.05%).
      CONCLUSION: S. haematobium transmission has been sustained in the reservoir since
      the outbreak was first reported in 1988. Mass treatment with praziquantel was
      conducted 8 years ago (2001) in two of the communities. However, the infection
      has persisted due to lack of pipe borne water and safe waste disposal system.

PMID- 23112996
TI  - Different prevalence of chronic-non-infectious diseases.
AB  - Inflammatory bowel disease, coronary artery disease, cerebrovascular disease,
      hypertension, diabetes, tumours, are examples of chronic degenerative diseases
      that have a high prevalence in developed nations. These chronic-non-communicable
      diseases have multifactorial aetiologies that considered to be caused by the
      interaction of environmental risk factors with multiple predisposing genes.
      Genetic researches on these diseases have traditionally focused on investigation
      aimed at identifying disease-susceptibility genes. Recent evidence suggests that
      somatically acquired DNA mutations may also contribute significantly to the
      pathogenesis of these disease states such as coronary artery disease indicating a
      similarity between the atherosclerotic and carcinogenic processes. The high
      incidences and prevalence of these chronic diseases in the Western World in
      comparison with the East and changing trends in disease incidence (seen in many
      countries) provide strong evidence that those environmental factors as playing a
      major influence in disease-expression. There is an ample reason to believe that
      environmental factors have contributed to inducing alterations in genetic code in
      precedent generations, which were subsequently inherited and further modified by
      modern life style activities. Consequently, we now see the appearance of chronic
      degenerative diseases and their higher incidences in the Western nations as
      compared with the Eastern ones.

PMID- 23112997
TI  - Genetic Analysis of Oculocutaneous Albinism Type1A (OCA1A) in an Iranian Family.
AB  - BACKGROUND: Oculocutaneous albinism type1 (OCA1) is characterized by the absence
      of melanin pigmentation. The mutation on TYR gene makes OCA1 as an autosomal
      recessive genetic disorder. In this study, we delineated the genetic analysis of
      an Iranian family with four members affected with OCA1. METHODS: Clinical exams
      and paraclinical test were performed for all patients of the case family, also
      proband, her husband, and her parents. Pedigree chart was drawn too. We extracted
      the genomic DNA from the leukocytes of seven members of the family. Haplotype
      analysis at the TYR locus was done and informative microsatellite markers were
      employed. In order to amplify the entire coding region of the TYR gene, for
      bidirectional direct sequencing mutation analysis, eight sets of primers were
      used. RESULTS: Our patients were diagnosed as affected with Oculocutaneous
      albinism type1a. Analysis of pedigree pattern showed an autosomal recessive
      inheritance. Analysis with different markers in chromosomes 5, 6, 9, 11 and 15
      showed that cause of albinism in our case family was on chromosome 11 (D11S1887
      marker was informative). CONCLUSIONS: The results offered a more developed method
      of diagnosis for OCA1 carrier identification and genetic counseling for OCA1
      affected families as well; also submit a sample of mutation involved with
      oculocutaneous albinism in Iran. Genetic analysis is necessary for determining
      the type of albinism in an individual patient.

PMID- 23112998
TI  - Human Subcutaneous Dirofilariasis due to Dirofilaria (Nochtiella) repens:
      Clinically Suspected as Cutaneous Fascioliasis.
AB  - BACKGROUND: The significant increase in the number of human subcutaneous
      dirofilariasis in recent years, suggests the appearance of a new health problem
      in the old world with most cases reported from Mediterranean countries. Besides
      the present case, eleven cases of human subcutaneous dirofilariasis have been
      detected in Iran, three of which belong to Gilan Province, northern Iran.
      METHODS: We present an autochthonous case of subcutaneous Dirofilaria repens
      infection in a 39-year-old woman from Kouchesfahan district of Gilan Province,
      manifest as an itching and highly erythmatous subcutaneous tender nodule on her
      right thigh. The nodule was excised by a dermatologist as a suspected case of
      cutaneous fascioliasis. RESULTS: Microscopic examination of the excised nodule
      revealed the presence of D. repens. CONCLUSION: Since Gilan Province is the
      endemic region for human fascioliasis and several cases of cutaneous fascioliasis
      have been detected in the province during last two decades, we propose the
      physicians and pathologists to take in to account subcutaneous dirofilariasis as
      an emergent zoonosis causing dermal and visceral lesions which may sometimes
      misdiagnose as malignant tumors, and also as differential diagnosis of cutaneous
      fascioliasis.

PMID- 23112999
TI  - Association between Alzheimer's Disease and Apolipoprotein E Polymorphisms.
AB  - BACKGROUND: Alzheimer's disease as a neurodegenerative disorder is the commonest
      type of dementia. A growing number of genes have been reported as the risk
      factors, which increase the susceptibility to Alzheimer's disease. Apolipoprotein
      E (APOE), which its epsilon4 allele has been reported as a risk factor in late
      onset Alzheimer's disease (AD), is the main cholesterol carrier in the brain. The
      main goal of this study was to assess the role of APOE genotypes and alleles in
      AD in Iranian population. METHODS: This study was performed in Tehran, Iran from
      2007 to 2008. Totally, 154 AD cases and 162 control subjects from Iranian
      population were genotyped for APOE using PCR method. Genotype and alleles
      frequencies for APOE were calculated and compared between AD case and control
      subjects by chi2 or Fisher's exact test. Type one error assumed less than 0.05.
      RESULTS: The frequency of epsilon2epsilon3 genotype was significantly higher in
      control subjects than AD patients was (13.5% versus 5.2%, P< 0.05) and
      epsilon3epsilon4 genotype frequency was significantly higher in AD cases compared
      with control subjects. APOE -epsilon2 allele frequency in cases was lower than
      that of control subjects but this difference was not significant (4.2% versus
      7.7%). CONCLUSION: It seems that individuals carrying epsilon4 allele, develop AD
      6.5 times more than non-carriers do (OR= 6.566, 95% CI= 2.89-14.92). It has been
      reported that epsilon4 allele acts in dose- age-dependent manner but we have
      shown that the risk of developing AD in male APOE -epsilon4 allele carriers is
      higher than that of female epsilon4 carriers.

PMID- 23113000
TI  - Upflow Sludge Blanket Filtration (USBF): an Innovative Technology in Activated
      Sludge Process.
AB  - BACKGROUND: A new biological domestic wastewater treatment process, which has
      been presented these days in activated sludge modification, is Upflow Sludge
      Blanket Filtration (USBF). This process is aerobic and acts by using a sludge
      blanket in the separator of sedimentation tank. All biological flocs and
      suspended solids, which are presented in the aeration basin, pas through this
      blanket. The performance of a single stage USBF process for treatment of domestic
      wastewater was studied in laboratory scale. METHODS: The pilot of USBF has been
      made from fiberglass and the main electromechanical equipments consisted of an
      air compressor, a mixing device and two pumps for sludge return and wastewater
      injection. The wastewater samples used for the experiments were prepared
      synthetically to have qualitative characteristics similar to a typical domestic
      wastewater (COD= 277 mg/l, BOD(5)= 250 mg/l and TSS= 1 mg/l). RESULTS: On the
      average, the treatment system was capable to remove 82.2% of the BOD(5) and 85.7%
      of COD in 6 h hydraulic retention time (HRT). At 2 h HRT BOD and COD removal
      efficiencies dramatically reduced to 50% and 46.5%, respectively. CONCLUSION:
      Even by increasing the concentrations of pollutants to as high as 50%, the
      removal rates of all pollutants were remained similar to the HRT of 6 h.

PMID- 23113001
TI  - Nationwide report on the findings of integrated school health screening program
      in iran.
AB  - BACKGROUND: Screening of students' health problems could lead to timely
      prevention and control of many health disorders. This study aimed to determine
      the nationwide prevalence of common disorders through school health screening
      program in Iran METHODS: This cross-sectional national screening program was
      conducted in 2007-2008 among first- and third-grade-students in primary schools,
      first-grade-students of middle and high schools of all provinces in Iran.
      RESULTS: Data were obtained from 3,124,021 (81.9%) students reported from the
      whole country classified into 33 geographical zones. Of total students studied,
      12.48% had weight abnormalities, 4.77% had visual disorders, 3.95 % had head
      lice, 2.24% had behavioral disorders, and 0.6% had hearing disorders. Among
      students studied, 0.4%, 0.7%, 0.4% and0.8% had endocrine, psychological,
      neurological and genitourinary disorders, respectively. In addition, 2.1%, 1.9%,
      1.8%, 0.8%0.5%, 0.3% and 0.3% of students had ear, nose & pharynx disorder,
      anemia, skin & hair, cardiac, abdominal, vertebral and lung problems,
      respectively. In elementary schools, 57.6% of first-grade-students with at least
      one disorder were managed in outpatient settings and 6% of them were hospitalized
      for more investigation. Among third-grade-students of elementary schools, these
      values corresponded to 13.2% and 1.1%, respectively. Among first grade students
      of middle and high schools, this prevalence was 58.5% and 44.6% and 1.2% and 0.3%
      of students were hospitalized for more investigation. CONCLUSION: This integrated
      school screening program revealed a considerably high prevalence of health
      disorders among school students. These results might help health policy makers to
      design future health promoting programs.

PMID- 23113002
TI  - The Effectiveness of Educational Intervention in the Health Promotion in Elderly
      people.
AB  - BACKGROUND: More than 8% of Iran's populations are elderly. The greatest
      challenge in this generation is improvement of health and quality of life. So we
      decided to perform an interventional study with the aim of promoting the health
      of the elderly. METHODS: This study was a community interventional in Ekbatan
      Complex. Subjects were elderly. At first, need assessment was done with the
      participation of 200 elderly by questionnaire. Based on the need assessment, we
      designed the educational interventions in different fields such as nutrition,
      mental health, and exercise and then, we compared the results. RESULTS: 0ne
      hundred elderly participated as interventional group. There were 86% women and
      24% of men. Almost 59% were in the 60-69 age group. More than 1/4 of the subjects
      were university graduates. Pre and post interventional groups were matched in
      age, education and gender. Regarding nutrition, second priority food in women
      aged 60-69 was rice and after the intervention, it was changed to vegetables (P=
      0.05) but in other age groups and in the men's groups no difference were noted.
      Aerobic exercises in women has increased after the intervention (P= 0.01). With
      regards to mental health, life satisfaction among women under study has increased
      from 68% to 90% after the intervention (P= 0.01). Feeling happy most of the time
      has increased from 53% to 83% in women aged 60-69 (P= 0.01) and in men from 64%
      to 83% (P= 0.05) respectively. CONCLUSION: Policymakers should design long-term
      educational programs to promote the elderly lifestyles.

PMID- 23113003
TI  - Aflatoxin Detoxification in Rice using Citric Acid.
AB  - BACKGROUND: Aflatoxins cause health hazards to human and animals and has also
      economical problems. Therefore, the detoxification effect of citric acid was
      investigated in rice as the main food of Iranian people. METHODS: Initially 275
      samples of rice were examined for aflatoxins by HPLC. The aflatoxins contaminated
      samples were later treated by aqueous citric acid and detoxification of
      aflatoxins were quantified using HPLC. RESULTS: Among the 275 samples analyzed,
      aflatoxin B(1) and aflatoxin B(2) were detected in 211(76.72% of total) samples.
      Aflatoxin B(1) was detected in 203(73.82% of total) samples with a mean and
      standard deviation of 2.3+/-10.21ppb. Aflatoxin B(2) together with aflatoxin B(1)
      were detected in only 8(2.91% of total) samples with a mean and standard
      deviation of 1.38+/-2.7ppb of aflatoxin B(2) and 2.99+/-1.56 of aflatoxin B(1)
      respectively. Aflatoxin B(1) level in 5 samples (1.82%) was above the maximum
      tolerated level of aflatoxin B(1) in Iran (5ppb). However considering the Iranian
      maximum tolerated level for aflatoxins in rice (30ppb), only 3(1.09%) samples
      were above the 30ppb and also in regard to the European maximum tolerated level
      for aflatoxins in rice (4ppb), only 9(3.27%) samples were considered as higher
      than 4ppb. CONCLUSION: The HPLC assay showed that although aflatoxins with a
      concentration of <30 and <4 ppb in the rice samples were completely degraded, but
      97.22% degradation occurred in rice contaminated with >=30 and >=4ppb when
      treated with 1N citric acid. These results revealed the efficacy of 1N citric
      acid in reducing aflatoxins levels in rice.

PMID- 23113004
TI  - Impact of Care and Social Support on Wellbeing among people living with HIV/AIDS
      in Nigeria.
AB  - BACKGROUND: Availability of antiretroviral therapies has transformed AIDS into a
      manageable chronic condition and improved well-being among people living with
      HIV/AIDS (PHA) in developed countries. In developing countries however, such
      transformations are yet to occur due to socio-economic, systemic and
      environmental constraint. This study examined the impact of social, economic,
      psychological and environmental factors on health and wellbeing among PHA living
      in southwest Nigeria. METHODS: Using qualitative participatory methodology, 50
      HIV positive people, 8 health personnel and 32 care providers were interviewed to
      explore how care and social support affect wellbeing among PHA in view of
      constraints to accessing antiretroviral drugs. Analysis of data used the grounded
      theory (GT) approach to identify themes, which are considered crucial to the
      wellbeing of PHA. RESULTS: The findings highlight several factors, apart from
      antiretroviral drugs, that impact the wellbeing of PHA in southwest Nigeria.
      These include concerns about deteriorating physical health, family and children's
      welfare, pervasive stigma, financial pressures and systemic failures relating to
      care among others. We describe how psychosocial and social support structures can
      considerably contribute to improving health outcomes among them because of how
      they affect the functioning of immune system, self-care activities and other
      illness behaviours. CONCLUSION: We recommend that interventions should address
      the psychosocial, socio-economic and other systemic issues that negatively
      influence the wellbeing of PHA and governments need to strengthen the policy
      environment that empowers PHA support groups.

PMID- 23113005
TI  - Genotyping Pattern among Iranian HCV Positive Patients.
AB  - BACKGROUND: Successful treatment to eliminate HCV RNA depends on the identified
      genotype. In the present study, we compared the frequency of different HCV
      genotypes, during four years study (2004 till 2008). METHODS: Sera specimens were
      received from 16 provinces of Iran. We used High Pure Viral Nucleic Acid
      Purification kit for extraction and samples were tested with improved form of RT
      PCR technique. HCV genotypes were determined using Amplisense PCR kit and
      Amplicor HCV Monitoring Version 2 test utilized a reverse transcription (RT)-PCR
      approach to quantitative HCV RNA. Two hundreds six HCV positive specimens were
      entered to the study out of 389 tested samples. RESULTS: Type 3a was the most
      frequent type (46.6%), followed by type 1 (including 1a and 1b with 25.73% and
      17.47% for each respectively) with 43.2%. Looking through collected results of
      the four years study confirmed the rate of HCV infection in those single
      genotypes 1b, 3a were slightly increased from 12.22% and 38.88% in the first year
      to 18.66 and 46.51% in the fourth year of the study period. CONCLUSION: The
      analyzed data proved that some patients were infected with two different types.
      High viral load was also more correlated to genotype 1 than other types.

PMID- 23113006
TI  - Prevalence of Rotavirus, Adenovirus, and Astrovirus Infections among Patients
      with Acute Gastroenteritis in, Northern Iran.
AB  - BACKGROUND: The aim of the study was to determine the incidence of non-bacterial
      acute gastroenteritis associated with diarrheal diseases in Mazandaran Province,
      northern Iran. METHODS: A total of 400 symptomatic cases from patients with acute
      gastroenteritis from Mazandaran Province in Iran were screened using EIA method
      for the presence of rotavirus, adenovirus and astrovirus during 2005-2006. Chi
      square tests were used for testing relationships between different variables.
      RESULTS: Rotavirus, adenovirus and astrovirus were detected in 62%, 2.3%, and 3%
      of samples, respectively. The maximum rate of rotaviruses was detected in the <1
      year-old age group, while minimum rate was found in the 10 years and older age
      group. Astrovirus and adenovirus were detected predominantly in the 2-5-year-old
      age group of children, with a prevalence of 8.3% and 3.5% respectively. All
      studied viral gastroenteritis peaked in the winter, and minimum rate were found
      in summer. CONCLUSION: Our statistical analyzes indicated that viral
      gastroenteritis, especially Rota-viral, had the highest number of occurrences in
      colder seasons notably in winter and more frequently were observed among younger
      children.

PMID- 23113007
TI  - Does group prenatal care affect satisfaction and prenatal care utilization in
      Iranian pregnant women?
AB  - BACKGROUND: The need to provide high quality prenatal care services, which take
      account of women's views and specifically address their need for information,
      support and communication, has been advocated and group prenatal care, had been
      suggested as one of the ways to achieve this objective. The purpose of this study
      was to examine the impact of group versus individual prenatal care on
      satisfaction and prenatal care use. METHODS: This was a cluster-randomized
      controlled trial with the health center as the randomization unit that conducted
      in 2007. Satisfaction was measured through a standardized questionnaire, and the
      Kotelchuck Adequacy of Prenatal Care Utilization Index was used to measure
      prenatal care utilization. RESULTS: We recruited 678 women (group prenatal care,
      (N= 344) and individual prenatal care, (N=334) in the study. Women in group
      prenatal care model were more satisfied than women in individual prenatal care
      model in all areas evaluated, including information, communication, co-ordination
      and quality of care. Group care women were significantly more likely to have
      adequate prenatal care than individual care women were (OR=1.35 95% CI=1.26
      1.44). CONCLUSIONS: Group prenatal care was associated with a significant
      improvement in client satisfaction and prenatal care utilization. This model of
      care has implications for the planning and provision of prenatal services within
      public health system, which is moving toward a better quality health care, and
      increasing use of services.

PMID- 23113008
TI  - Molecular epidemiology of aminoglycosides resistance in acinetobacter spp. With
      emergence of multidrug-resistant strains.
AB  - BACKGROUND: Acinetobacter spp. is characterized as an important nosocomial
      pathogen and increasing antimicrobial resistance. Our aim was to evaluate
      antimicrobial susceptibility and aminoglycosides resistance genes of
      Acinetobacter spp. isolated from hospitalized patients. METHODS: Sixty isolates
      were identified as Acinetobacter species. The isolates were tested for antibiotic
      resistance by disc diffusion method for 12 antimicrobials. The presence of aphA6,
      aacC1 aadA1, and aadB genes were detected using PCR. RESULTS: From the isolated
      Acinetobacter spp. the highest resistance rate showed against amikacin,
      tobramycin, and ceftazidim, respectively; while isolated bacteria were more
      sensitive to ampicillic/subactam. More than 66% of the isolates were resistant to
      at least three classes of antibiotics, and 27.5% of MDR strains were resistant to
      all seven tested classes of antimicrobials. The higher MDR rate presented in
      bacteria isolated from the ICU and blood samples. More than 60% of the MDR
      bacteria were resistance to amikacin, ceftazidim, ciprofloxacin,
      piperacillin/tazobactam, doxycycline, tobramycin and levofloxacin. Also, more
      than 60% of the isolates contained phosphotransferase aphA6, and
      acetyltransferase genes aacC1, but adenylyltransferase genes aadA1 (41.7%), and
      aadB (3.3%) were less prominent. 21.7% of the strains contain three
      aminoglycoside resistance genes (aphA6, aacC1 and aadA1). CONCLUSION: The rising
      trend of resistance to aminoglycosides poses an alarming threat to treatment of
      such infections. The findings showed that clinical isolates of Acinetobacter spp.
      in our hospital carrying various kinds of aminoglycoside resistance genes.

PMID- 23113009
TI  - Distribution of beta-Globin Gene Mutations in Thalassemia Minor Population of
      Kerman Province, Iran.
AB  - BACKGROUND: Mutations in beta-globin gene may result in beta-thalassemia major,
      which is one of the most common genetic disorders in Iran and some other
      countries. Knowing the beta-globin mutation spectrum improves the efficiency of
      prenatal diagnosis in the affected fetuses (major beta-thalassemia) of
      heterozygote couples. METHODS: Couples with high hemoglobin A(2) and low mean
      corpuscular volume were studied as suspicious of beta-thalassemia carriers in
      Genetic Laboratory of Afzalipour Hospital, Kerman, Iran. We used amplification
      refractory mutation system, reverse hybridization, and DNA sequencing to
      determine the spectrum of beta-globin gene mutation in the people who involved
      with beta-thalassemia minor in this province. RESULTS: Among the 266 subjects, 17
      different types of mutation in beta-globin gene were identified. Three of the
      mutations account for 77.1% of the studied cases. IVSI-5(G> C) was the most
      frequent mutation (66.2%) followed by IVSII-I (G> A) (6%) and Fr 8-9 (+G) (4.9%).
      The less frequent mutations include: IVSI-6(T> C), codon 15 (G>A), codon 44 (-C),
      codon 39 (C>T), codon 8 (-AA), codon30 (G> C), IVSI-110 (G > A), codon 36-37 (
      T), 619bp deletion, codon 5 (-CT), IVSI-25bp del, codon 41-42(-TTCT), IVSI-I (G>
      A), and betant30 (T>A) were accounted for 19.5%. Unknown alleles comprised 3.4%
      of the mutations. CONCLUSION: However, the frequencies of different mutations
      reported here are significantly different from those found in other part of the
      world and even other Iranian provinces. Reporting a number of these mutations in
      the neighboring countries such as Pakistan can be explained by gene flow
      phenomenon.

PMID- 23113010
TI  - The Effects of Health Education through Face To Face Teaching and Educational
      Movies, on Suburban Women in Childbearing Age.
AB  - BACKGROUND: The aim of the study was to compare the effects of 'face-to-face
      education' and 'educational movies' on 'knowledge' and 'practice' of women of
      child-bearing-age, in terms of health-care during pregnancy and during infancy in
      a suburban region near Tehran City, Iran. METHODS: In this quasi-experimental
      study, the sample included 873 married women. Questionnaires for knowledge and
      practice assessment were designed. The women were assigned to three groups:
      control (group I), face-to-face education (group II), and educational movie
      (group III). Knowledge questionnaires were completed before and immediately after
      intervention. Practice questionnaires were completed before and three months
      after intervention. Both questionnaires consisted of two types of questions: type
      A (concerning infant care issues) and type B (concerning prenatal health care).
      RESULTS: There was a significant difference in post-test knowledge between groups
      I and II and between groups I and III, but not between groups II and III. In
      terms of post-test practice, the changes were determined for every individual
      question, and significantly, better results were seen in group II, especially
      concerning type B questions. CONCLUSION: Face to face education lead to better
      practice than educational movies. In addition, significantly better practice
      occurred regarding child health care issues rather than prenatal issues in both
      groups. Realistic and tangible issues, those easy to practice, and with little or
      no economical burden imposed on the family, progressed from the knowledge state
      to the practice state more successfully in both groups.

PMID- 23113011
TI  - Overall, and specific life satisfaction domains: preliminary Iranian students
      norms.
AB  - BACKGROUND: The WHOQOL-BREF is one of the best-known instruments that have been
      developed for cross-cultural comparisons of quality of life and currently it is
      available in more than 40 languages. Current study was done to provide: (1) the
      psychometrics properties of the Iranian version of WHOQOL-BREF and (2) the norm
      scores for satisfaction with life overall and satisfaction with specific Life
      domains of Iranian students. METHODS: A sample of 1000 Iranian undergraduate
      students, (Males= 490 and Females= 510) were pooled using multi-stage random
      method and asked to complete the Iranian version of the WHOQOL-BREF. RESULTS: The
      results of current study indicated that a good internal consistency (alpha =
      0.89) for WHOQOL-BREF (26 items) as well as four domain ratings. Our findings
      also showed no floor or ceiling effect for the 4 domains as well overall QOL and
      general health facets. Moreover, General norms for the satisfaction with life
      overall, general health and satisfaction with specific life domains (physical
      health, psychological well-being, social relationships, and environmental
      support) were obtained using WHOQOL-BREF. CONCLUSION: The Iranian version of
      WHOQOL-BREF was deemed reliable in assessing the quality of life of a student
      population in Iran. Our results of calculating and presenting norm scores for
      satisfaction ratings can be used as preliminary Iranian students' norms for those
      researchers who are interested in measuring and interpreting satisfaction ratings
      using WHOQOL-BREF.

PMID- 23113012
TI  - Motorcycle fatal accidents in khorasan razavi province, iran.
AB  - BACKGROUND: All over the world motorcycle accident are one of the major causes of
      road death and injury. This study aimed to determine the pattern of Motorcycle
      Fatal Accidents in Mashhad-Iran. METHODS: This descriptive cross-sectional study
      was carried out in 2006 to analyze the epidemiological pattern of the motorcycle
      accident in Mashhad, North-Eastern Iran. Three hundred fifty cases of motorcycle
      accidents were included. Data gathering tool was a standard questionnaire. The
      compiled data were analyzed using SPSS11 and chi(2) test. The significance level
      was considered 0.05 in all statistical tests. RESULTS: In the time span of the
      study, 350 cases of motorcycle accident occurred, most of which happened at 8pm
      to 12pm. In 119 cases, the motorcyclist was the blameful rider. Generally, 84.2%
      of the motorcycle riders did not have safety helmets. About two third of blameful
      motorcycle riders (63.1%) were less than 25 years old. The major cause of the
      accidents (55.1%) was due to neglecting the Yield Right of Way. Motorcycle riders
      endanger pedestrian, other drivers, passengers and their own life. CONCLUSION:
      Paying attention to cultural and instructional issues of correct motorcycle
      riding and performing appropriate monitoring in traffic and transportation system
      such as honoring our and others safety and setting limitations on using this
      vehicle by the youth is of great importance.

PMID- 23113013
TI  - Metaplot: a novel stata graph for assessing heterogeneity at a glance.
AB  - BACKGROUND: Heterogeneity is usually a major concern in meta-analysis. Although
      there are some statistical approaches for assessing variability across studies,
      here we present a new approach to heterogeneity using "MetaPlot" that investigate
      the influence of a single study on the overall heterogeneity. METHODS: MetaPlot
      is a two-way (x, y) graph, which can be considered as a complementary graphical
      approach for testing heterogeneity. This method shows graphically as well as
      numerically the results of an influence analysis, in which Higgins' I(2)
      statistic with 95% (Confidence interval) CI are computed omitting one study in
      each turn and then are plotted against reciprocal of standard error (1/SE) or
      "precision". In this graph, "1/SE" lies on x axis and "I(2) results" lies on y
      axe. RESULTS: Having a first glance at MetaPlot, one can predict to what extent
      omission of a single study may influence the overall heterogeneity. The precision
      on x-axis enables us to distinguish the size of each trial. The graph describes
      I(2) statistic with 95% CI graphically as well as numerically in one view for
      prompt comparison. It is possible to implement MetaPlot for meta-analysis of
      different types of outcome data and summary measures. CONCLUSION: This method
      presents a simple graphical approach to identify an outlier and its effect on
      overall heterogeneity at a glance. We wish to suggest MetaPlot to Stata experts
      to prepare its module for the software.

PMID- 23113014
TI  - Plasmodium vivax MSP-3beta Gene as a Genetic Marker for the Parasite Detection in
      Comparison with Ssrrna Gene.
AB  - BACKGROUND: The importance of accurate diagnosis of all of major diseases cannot
      be underestimated and efficient laboratory testing is vital to identifying and
      treating life-threatening illnesses including malaria. In this study, we compared
      the potential of one of merozoite surface protein genes, PvMSP-3beta, for
      detection of Plasmodium vivax in blood samples by PCR with routinely used marker,
      ssrRNA gene. METHODS: One hundred P. vivax microscopy-positive blood samples were
      simultaneously tested with two genetic markers, including PvMSP-3beta gene and
      ssrRNA gene by PCR and nestedPCR method, respectively, and their sensitivity and
      specificity in detection of P. vivax was compared. RESULTS: An important
      difference was seen in sensitivity between the 2 genetic markers, 100% in case of
      ssrRNA gene vs. 95% of PvMSP-3beta gene. The specificity of the two markers was
      same (100%). Microscopic diagnoses of thick and thin blood smears was used as
      "golden standard" method. CONCLUSION: Due to critical importance of accurate
      detection of the parasite in malarious area, the PvMSP-3beta gene cannot be a
      suitable marker for detection of P. vivax in blood sample by PCR. More
      investigations are needed to find other valid markers.

PMID- 23113015
TI  - Imipenem Resistance among Gram-Negative and Gram-Positive Bacteria in
      Hospitalized Patients.
AB  - BACKGROUND: Recent analyses of hospital outbreaks have documented the spread of
      resistance to imipenem, which is currently a major problem among gram positive
      and gram-negative bacteria. The aim of this study was to describe the rate of
      gram-positive and gram-negative isolates resistance to imipenem as an antibiotic.
      METHODS: Recorded files of 242 hospitalized patients with at least one sample of
      positive culture specimens in one of the two general hospitals of Shahid Beheshti
      and Naghavi in Kashan, Iran in 2005 were randomly selected and reviewed. All
      strains were tested for antibiotic susceptibility by Disk Diffusion and were
      designated for imipenem. RESULTS: Escherichia coli (21.9%), Kelebsiella (19.8%)
      and coagulase-negative Staphylococci (17.8%) were the most common isolated
      organisms. Imipenem had coverage against 96.2% of Escherichia coli, 58.4% of
      Kelebsiella, 79.1% of coagulase-negative Staphylococci, 81.8% of Pseudomonas
      aeruginosa, and 85.7% of Entrococci isolates. Proteus and Salmonella isolates
      susceptibility to imipenem was 100%. CONCLUSION: Susceptibility of Escherichia
      coli, Salmonella and Proteus to imipenem is satisfactory; however, the
      susceptibility of Pseudomonas aeruginosa to this antibiotic was dramatically
      lower in our region. Because of the major health problems caused by imipenem
      resistance, attempts have been made to organize a national surveillance program
      in our country.

PMID- 23113016
TI  - A systematic review of the extent, nature and likely causes of preventable
      adverse events arising from hospital care.
AB  - BACKGROUND: Understanding the nature and causes of medical adverse events may
      help their prevention. This systematic review explores the types, risk factors,
      and likely causes of preventable adverse events in the hospital sector. METHODS:
      MEDLINE (1970-2008), EMBASE, CINAHL (1970-2005) and the reference lists were used
      to identify the studies and a structured narrative method used to synthesise the
      data. RESULTS: Operative adverse events were more common but less preventable and
      diagnostic adverse events less common but more preventable than other adverse
      events. Preventable adverse events were often associated with more than one
      contributory factor. The majority of adverse events were linked to individual
      human error, and a significant proportion of these caused serious patient harm.
      Equipment failure was involved in a small proportion of adverse events and rarely
      caused patient harm. The proportion of system failures varied widely ranging from
      3% to 85% depending on the data collection and classification methods used.
      CONCLUSION: Operative adverse events are more common but less preventable than
      diagnostic adverse events. Adverse events are usually associated with more than
      one contributory factor, the majority are linked to individual human error, and a
      proportion of these with system failure.

PMID- 23113017
TI  - Medical tourism-A New Arena.
AB  - Globalisation has given birth to medical tourism. Health and medical tourism are
      the fastest growing segments in not only developed nations but in developing
      countries too. India has become a hot destination, as the Indian medical
      standards match up to the highly prescribed international standards at a very low
      cost. However, it is an unmixed blessing; along with advantages, it has many
      unintended side effects also.

PMID- 23113018
TI  - Changing pattern of mortality trends in iran, South, South-west Asia and world,
      1970-2010.
AB  - BACKGROUND: Mortality refers to the death that occurs within a population. It is
      linked to many factors such as age, sex, race, occupation and social class. The
      incidence and prevalence of mortality could affect the population's standard of
      living and health care. The aim of this study was to explore the pattern of
      mortality trends in Iran, south-south west Asia and the world in 1970-2010.
      METHODS: A descriptive study was conducted on the registered data in the
      Statistical Center of Iran and National Organization of Civil Registration. The
      data were analyzed using statistical methods and graphs. Finally, the analyzed
      data were compared with the world and south-south west Asia data. RESULTS: In
      Iran, 61.1% of all the registered deaths were in male and 60.4% were in urban
      areas. Crude death rate, infant mortality rate and under five mortality rate
      decreased from 13, 164 and 281 per 1000 in 1970-75 to the estimated values of 5,
      25 and 35 per 1000 in 2005-2010, respectively. CONCLUSION: The results showed
      that similar to other countries, the trends of all mortality indicators in Iran
      have been changed and decreased, which is related to many factors such as
      improvement health situation and medical interventions.

PMID- 23113019
TI  - Gastric cancer prevalence, according to survival data in iran (national study
      2007).
AB  - BACKGROUND: Gastric cancer is a common and lethal disease throughout the world.
      In Iran with 7300 new cases annually, it is the first cause of cancer related
      death in both sexes. Regarding the high incidence (10.5/100000 individuals) of
      gastric cancer and priority of prevalence index in cancer management, in this
      study we tried to determine 1, 2-3 and 4-5 year point prevalence of the disease
      according to survival data. METHOD: Survival and incidence data were used for
      determination of cancer prevalence. Incidence data were extracted from cancer
      registry in Iran and survival data were determined in a descriptive study by
      following up 3439 gastric cancer patients in Cancer Research Center (CRC). 1, 2-3
      and 4-5 year prevalence was estimated from incidence rates in different years and
      the proportion of patients surviving 0.5, 1.5, 2.5, 3.5 and 4.5 years from the
      time of diagnosis. RESULTS: patients with survival of 0.5, 1.5, 2.5, 3.5 and 4.5
      years from the time of diagnosis were 46.38%, 26 %, 19.36%, 15.47% and 12.8%
      respectively. The prevalence of 1, 2-3 and 4-5 year was 3392, 3118and 1824
      respectively. The cumulative 5 year prevalence was 8334 cases. CONCLUSION: These
      estimates of the point prevalence of gastric cancer at 1, 2-3 and 4-5 years are
      applicable to the evaluation of initial treatment, clinical follow-up, and point
      of cure. Therefore 1, 2-3 and 4-5 year point prevalence estimates, are necessary
      in health service planning for gastric cancer management and should be considered
      by public health managers.

PMID- 23113020
TI  - The Study of Total IgE Reference Range in Healthy Adults in Tehran, Iran.
AB  - BACKGROUND: IgE is an antibody class that regarded as an important factor in the
      pathogenesis of allergic diseases, asthma, immune responses to parasitic
      infection and it could be responsible for the late- phase allergic response. The
      objective of this study was to evaluate total IgE in healthy Iranian adults,
      establishment of reference range of total IgE and assess helpfulness of this
      value in clinical diagnosis atopic and allergic diseases. METHOD: Three hundred
      sixty six healthy adults from blood transfusion volunteers (18 to 60 years) were
      selected in this study. A specific questionnaire (including demographic factors,
      smoking status and ...) was filled out for each person. Also, we evaluated effect
      of race and education on total IgE. These adults had no history of allergic
      disease. The total serum IgE level using a commercial enzyme immunoassay and CBC
      (Eosinophil count) was determined in them. RESULTS: Mean of age was 37.32+/-
      10.93 yrs and 219 cases were males and 147 females. The geometric mean of total
      IgE was 20.84 IU/ml (2-373 IU/ml) (95% percentile= 250) (95% confidence
      interval=46.27-62.70). No differences was observed between mean of IgE log in
      males and females (P= NS) but mean of total IgE log in females is more than
      males. CONCLUSION: Normal range of serum total IgE obtained in this study could
      be helpful for diagnosis of IgE-dependent allergic disease, as reference ranges
      in Iranian healthy adults.

PMID- 23113021
TI  - The association of life style with hypertension in korean women.
AB  - BACKGROUND: This study examined the relationship between lifestyle factors and
      hypertension in Korean women. METHODS: The subjects were 8,836 women, aged 20 to
      81 yr, who visited a health promotion center for a medical check up during 2004
      2008. The diagnosis of hypertension was defined in the Joint National Committee
      on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7)
      report. Statistical significance was set at alpha<0.05 and SPSS ver. 12.0
      software (SPSS, Chicago, IL, USA) was used. RESULTS: The prevalence of
      hypertension was 12.8% in this study population. Multivariate logistic regression
      demonstrated that the odds ratio (95% CI) of hypertension across age groups were
      3.43 (1.68-7.02) for forties, 7.13 (3.48-14.60) for fifties, 12.97 (6.27-26.81)
      for sixties, and 24.28 (11.09-53.14) for over seventies compared to the twenties.
      In addition, compared with the normal weight group, the odds ratio (95% CI) of
      hypertension in the over-weight and obese groups were 2.41 (2.00-2.89) and 3.50
      (2.95-4.16), respectively. The odds ratio (95% CI) of hypertension in those who
      consumed more than 3 drinks per week was 1.88 (1.29-2.76, P=0.001) compared with
      non-drinking group. CONCLUSION: The significant risk factors of hypertension were
      age, BMI, and alcohol drinking among Korean women and that smoking, exercise, and
      diet were not related to the risk of hypertension.

PMID- 23113022
TI  - Vitamin d deficiency in healthy male population: results of the Iranian multi-
      center osteoporosis study.
AB  - BACKGROUND: The prevalence of vitamin D deficiency and its causative factors has
      been estimated more frequently in elder population, women, and patients with
      osteoporosis in different countries, but this issue is less defined in male
      population within different age groups especially in Asian countries. Therefore,
      we studied the role of effective factors in vitamin D deficiency and its
      prevalence in Iranian healthy men. METHODS: This study was a multi center and
      carried out in five metropolitans in Iran. Serum 25 Hydroxy vitamin D and other
      biochemical variables were determined in 2396 healthy men in late winter of 2001.
      RESULTS: 68.8% of participants suffered from vitamin D deficiency. Vitamin D
      levels were the highest in Bushehr (n= 111, 40.3%) (P< 0.05) and between Shiraz
      and Tabriz, Shiraz had the better values (P< 0.05). Tehran had the highest
      prevalence of vitamin D deficiency (n= 380, n= 85.7%). Geographical zone
      independently predicted vitamin D status (P< 0.05). There was not any association
      among age (r= 0.035, P> 0.05), physical activity (r= 0.023, P> 0.05), and
      exposure of face & hands to sunlight (r= 0.022, P> 0.05) with vitamin D levels.
      CONCLUSION: Prevalence of vitamin D deficiency in Iranian male population is
      high, considering Iranian cultural and geographical zones, food fortification and
      life style modification is recommended.

PMID- 23113023
TI  - Leber hereditary optic neuropathy: do folate pathway gene alterations influence
      the expression of mitochondrial DNA mutation?
AB  - BACKGROUND: Leber hereditary optic neuropathy (LHON) is an inherited form of
      bilateral optic atrophy leading to the loss of central vision. The primary cause
      of vision loss is mutation in the mitochondrial DNA (mtDNA), however, unknown
      secondary genetic and/or epigenetic risk factors are suggested to influence its
      neuropathology. In this study folate gene polymorphisms were examined as a
      possible LHON secondary genetic risk factor in Iranian patients. METHODS: Common
      polymorphisms in the MTHFR (C677T and A1298C) and MTRR (A66G) genes were tested
      in 21 LHON patients and 150 normal controls. RESULTS: Strong associations were
      observed between the LHON syndrome and C677T (P= 0.00) and A66G (P= 0.00)
      polymorphisms. However, no significant association was found between A1298C (P
      =0.69) and the LHON syndrome. CONCLUSION: This is the first study that shows
      MTHFR C677T and MTRR A66G polymorphisms play a role in the etiology of the LHON
      syndrome. This finding may help in the better understanding of mechanisms
      involved in neural degeneration and vision loss by LHON and hence the better
      treatment of patients.

PMID- 23113024
TI  - Evaluation of periodicals journals and community of medical sciences in iran.
AB  - BACKGROUND: Medical journals are scientific resources where utilization of
      knowledge is availed and create an environment of competitiveness. To speed up
      the growth and increase scientific production and in order that the rank of
      Iranian journals be defined regionally and globally, journal standardization is
      necessary. This study was done to evaluate the country's medical journals from
      2004-2006. METHODS: This is a descriptive/analytical study. Evaluation was based
      on the following; scientific credibility, registry and year of service, journal
      management, technical quality and accessibility. The number of journals evaluated
      during 2004-2006 were 86, 103 and 93, respectively and the process involved 3
      phases 1) defining the journal's structural indicators and designing the
      evaluation form 2) collection, sharing and final confirmation of information with
      the publication staff 3) data entry, analysis and ranking RESULTS: Improvement
      and growth of publication depends largely on 5 parameters and its development
      were based on the following; publication management (61.62 points), scientific
      credibility (43.80 points), quality of accessing the journals (37.05 points),
      quality of publication (14.80 points) and registry and year of service (0.02
      points). Based on the study, an upward developmental trend of the country's
      medical journals can be seen and the tools were sufficient in terms of validity
      and reliability. A revised and more comprehensive checklist that would evaluate
      all aspects of a publication basing on latest indicators is developed.
      CONCLUSION: Evaluations of the country's medical journals not only promote
      compliance to international standards but also led to more indexing of journals
      in accredited international indices.

PMID- 23113025
TI  - Diurnal variations in solar ultraviolet radiation on horizontal and vertical
      plane.
AB  - BACKGROUND: In general, measurements of solar ultraviolet (UV) radiation are
      related to horizontal surfaces. While the humans walking and standing outdoors
      expose to the natural solar UV radiation, their eyes, cheeks, extremities,
      trunks, or many other anatomical sites are close to vertical plane and random
      orient to different directions. In this study, we characterized the diurnal
      variations in solar UV on horizontal and vertical plane which may be helpful to
      obtain more relevant information on UV exposure of humans. METHODS: The UV
      exposure on vertical and horizontal plane were measured using Solar-UV Sensors in
      Shenyang (41 degrees 51"N, 123 degrees 27"E) and Sanya (18 degrees 19'N, 109
      degrees 42'E), PR China. RESULTS: As the well known, the diurnal variations in
      solar UV on horizontal plane in a sunny day exhibited unimodal distributions,
      reached a single UV peak exposure at around solar noon. However, the diurnal
      variations on vertical plane presented bimodal distributions, with two peaks in
      summer in Shenyang and Sanya, and a unimodal distribution in winter in Shenyang.
      In spring and autumn in Shenyang, the UV exposure around noon were slightly flat
      with no significant peaks but relative high. When the Solar Elevation Angle (SEA)
      is about 40 degrees , the vertical plane may potentially receiving maximal
      unweighted total solar UV radiation exposures. CONCLUSION: The results
      potentially showed that the protection of some vertical and near-vertical
      anatomical sites of human body from high UV exposure should not only focused on
      the periods of before and after noon especially in high SEA places.

PMID- 23113026
TI  - Effects of EPA and Vitamin E on Serum Enzymatic Antioxidants and Peroxidation
      Indices in Patients with Type II Diabetes Mellitus.
AB  - BACKGROUND: Diabetes mellitus is associated with chronic changes in peripheral
      arteries because of oxidative stress and insufficient antioxidative defense
      mechanism. Omega-3 fatty acid supplementation could be effective in some diabetes
      complications; however, polyunsaturated fatty acids may increase lipid
      peroxidation. This study aimed to determine whether eicosapentaenoic acid alone
      or in conjunction with vitamin E had differential effects on serum antioxidants
      and peroxidation indices. METHODS: This double-blind, placebo-controlled trial
      was carried out on 136 patients with type II diabetic mellitus (age 48.8+/-4.4
      yr, BMI 27.8+/-1.7 kg/m(2)). The four groups of the study either received two
      grams of omega-3 fatty acids, 400 IU of vitamin E, a combination of the two or
      placebo for three months. Their serum total antioxidant capacity, enzymatic
      antioxidants and peroxidation indices were assessed. RESULT: Fasting serum TAC
      increased in EPA+E (10.7%, P< 0.001) and E groups (7.5%, P< 0.05). SOD, G-PX and
      G-RD increased in EPA group (7.3%, 5.1%, and 8.4%, P< 0.05, respectively). MDA
      and protein carbonyl decreased in EPA and E groups (respectively, 12.5%, 7.6% P<
      0.05, P< 0.05; 13%, 15.3% P< 0.001, P< 0.05). After adjustment for baseline
      values, age, sex, BMI and duration of diagnosed diabetes, protein carbonyl
      decreased in EPA+E and E group (30.7%, 15.3%; P< 0.05 respectively) relative to
      the placebo group. CONCLUSION: EPA, by itself has a statistically significant
      effect on serum total antioxidant capacity, enzymatic antioxidants and
      peroxidation indices in diabetic patients compared to EPA+E or E alone. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT00817622.

PMID- 23113027
TI  - Iranian Female Adolescent's Views on Unhealthy Snacks Consumption: A Qualitative
      Study.
AB  - BACKGROUND: Given the increasing prevalence of obesity among Iranian adolescents
      and the role of consumption of unhealthy snacks in this issue, interventions that
      focus on factors influencing food choice are needed. This study was designed to
      delineate factors associated with unhealthy snack use among female Iranian
      adolescents. METHODS: The theory of Planned Behavior served as the framework of
      the study. Qualitative data were collected via nine focus group discussions in
      two middle schools (6(th) to 8(th) grades) in a socio-economically diverse
      district in the city of Tehran in spring 2008. The study sample included 90
      female adolescents aged 12-15 years. The sampling strategy was purposive method.
      Data analyzed using the "framework" method. RESULTS: Major factors identified by
      the respondents were taste, peer pressure, parental influence, easy access to
      unhealthy snacks, limited availability of healthy snacks, appeal of snacks,
      habit, high price of healthy snacks, and media advertisements. Nutritional value
      and healthiness was not one of the first priorities when buying snacks, as
      adolescents thought it was too early for them to worry about illness and adverse
      consequences of eating junk foods. CONCLUSIONS: For developing culturally
      sensitive evidence-based interventions that can motivate adolescents to choose
      healthy snacks, a broad range of factors should be taken into account.

PMID- 23113028
TI  - Effects of Two Temperature Storage Regimes on the Efficacy of 3 Commercial Gel
      Baits against the German Cockroach, Blattella germanica L. (Dictyoptera:
      Blattellidae).
AB  - BACKGROUND: To compare the effectiveness of 3 commercial gel bait formulations
      containing fipronil (Goliath((c)) Cockroach Gel 0.05% AI), chlorpyrifos-A (Clean
      Bait((c)) Gel, 2% AI), and chloropyrifos-B (Serpa((c)) Gel 2% AI) against German
      cockroaches (Blattella germanica) when stored at 23( degrees )C and 30( degrees )
      C after treatment. METHODS: Laboratory bioassays consisted of placing groups of
      fifteen cockroaches (a random combination of adult, mixed sex and large nymphs
      stage 6) into a 5 L cylindrical plastic container with one drop of product (avg
      0.10 g +/- 0.01 g) applied to a 76 mm x 26 mm glass microscope slide affixed to
      the bottom of each container (one product tested per container). Cumulative
      mortality was assessed at 6 h, 1, 2, 3, 4, and 5 d after application. To
      determine the further effects of storage temperature after treatment on residual
      activity of the gels, a drop of each product was applied to separate glass
      microscope slides and stored at either 23( degrees ) C (warm) or 30( degrees ) C
      (hot) under dark conditions for 0, 1, 7, 14, 30, 45, 60 and 90 d after
      application. RESULTS: Freshly applied baits (day 0) containing fipronil provided
      complete cockroach mortality (100%) within 5 d whereas chloryrifos-A and
      chlorpyrifos-B provided ~72% and 88% mortality, respectively. Generally,
      cockroach mortality was greater when gels were stored at 30( degrees )C compared
      with 23( degrees ) C. CONCLUSION: The fipronil gel formulation proved to be as
      efficacious as the chlorpyrifos gels and in some instances surpased the latter
      formulations depending on storage time and temperature by providing ~90%
      mortality at 90 d post treatment.

PMID- 23113029
TI  - In Silico Identification of Potential American Cockroach (Periplaneta americana)
      Allergens.
AB  - BACKGROUND: Cockroaches have been recognized as a powerful indoor allergen.
      Cockroach allergy can be a major factor in serious asthma and nasal allergy.
      Bioinformatics tools have been developed to identify potential allergens. The
      present study was conducted to identify potential allergens in Periplaneta
      americana (Linnaeus). METHODS: The study focused on the identification of
      potential allergens among the characterized proteins of P. americana using web
      based and publicly available allergen prediction tools that follow the FAO/WHO
      guidelines for prediction of allergenic proteins. P. americana protein sequences
      were retrieved from UniProtKB. The sequences obtained were analyzed using
      AlgPred. The potential allergens obtained were further analyzed by SDAP for
      confirmation. RESULTS: Protein sequences (233 cases) of P. americana were
      obtained from UniProtKB out of which 25 were known allergens. Out of the
      remaining 208 proteins, 102 potential allergens were predicted by AlgPred.
      However, only 9 were found to be potential allergens after screening with SDAP.
      Arginine kinases, RNA polymerase II subunit, parcxpwnx02, peptidylprolyl cis
      trans isomerase, hemocyanin subunit type I and type II, homologue of Sarcophaga
      proteinase and alpha amylase were confirmed to be potential allergens by SDAP.
      CONCLUSION: We have identified nine potential allergens in P. americana that may
      be used as preliminary support for further laboratory experiments.

PMID- 23113030
TI  - Neural tube defects in native fars ethnicity in northern iran.
AB  - BACKGROUND: Neural tube defects (NTD) are one of the leading causes of infant
      mortality worldwide. This study was designed to determine the prevalence of NTDs
      among native Fars ethnic groups during 1998-2005, and to identify maternal and
      demographic factors associated with NTDs. METHODS: We performed a descriptive
      cross-sectional hospital-based study in Dezyani Hospital, Gorgan, North of Iran,
      since January 1998 until December 2005. The design was based on a sample of
      30,639 births of native Fars ethnic groups. Data were analyzed by using spss
      V13.5 software and were compared with the chi-square test. RESULTS: The
      prevalence of NTDs in Native Fars during the 8-year period was 25.4 per 10000
      births (95% confidence interval: 20.1-31.8). The prevalence of NTDs was
      20.6/10000 and 30.6/10000 in males and females respectively but this difference
      was not significant. The prevalence of spina bifida, anencephaly and
      encephalocele were 12.7, 11.4 and 1.3 per 10000 respectively. The rate of NTD was
      48.9/10000 in newborns with mothers aged > 35 years. The highest rate of NTDs and
      spina bifida was in 2002. The highest and lowest rate of anencephaly was in 2005
      and 2003 respectively. Twenty eight percent of the parents had consanguineous
      marriages. Degree relatedness 3, 4, 5 and 6 of consanguineous marriages were
      12.8%, 9%, 3.8%, 2.5%, respectively. Also 47.5% of the parents resided in rural
      areas. CONCLUSION: This investigation showed that the rate of NTDs in Native Fars
      was higher in Iran. In addition, this rate is higher than the Canada and Ukraine
      and lower than Chinese people.

PMID- 23113031
TI  - Fungal Contamination of Indoor Public Swimming Pools, Ahwaz, South-west of Iran.
AB  - BACKGROUND: Using public swimming pools during different seasons and poor health
      behavior could be responsible in transmission of fungal disease through pool
      water and its environment. Therefore, this research was conducted to investigate
      fungal agents of indoor public swimming pools of Ahwaz, capital city of
      Khouzestan Province, south-west of Iran. METHODS: Ten indoor swimming pools of
      Ahwaz were investigated during two seasons for 6 months. Water specimens were
      collected by pump and environment samples including shower-bath area, margin of
      pool walls, dressing rooms, and slippers, by sterile carpet pieces. All specimens
      were cultured in SC and SCC culture media and fungal agents identification were
      based on macroscopic, microscopic characteristic and complement tests when it was
      necessary. Data analyzing was performed using SPSS version 13 for descriptive
      analyzing. RESULTS: A total of 593 samples were collected from different parts of
      pools. Interestingly in 13 samples from environmental places, dermatophytes were
      isolated as follows: Trichophyton mentagrophytes, T. rubrum, T. verrucosum and
      Epidermophyton floccosum 5, 4, 3 and 1 cases respectively. Ten cases of
      dermatophytes were isolated from floor of dressing area. Three hundred seventy
      two saprophytic fungi species and 32 yeasts were recovered from water and
      environment surfaces samples. Aspergillus, Penicillium and Mucor were the most
      common isolated saprophytic fungi. CONCLUSION: Existence of saprophytic fungi and
      yeast in pools water seems to be an indicator of their resistance to detergent
      agents. In addition, yeast water contamination could be from swimmers.
      Dermatophytes isolation from pools environment areas and foot washing sink,
      reveals the importance of public swimming pools in disease transmission. Because
      dressing places are being used by all of the swimmers, take care of hygienic
      discipline in these places should be noted by health policy markers.

PMID- 23113032
TI  - Neglected human fascioliasis case in a visceral leishmaniasis endemic area, north
      Western iran.
AB  - Ardabil Province, northwestern Iran, is endemic for visceral leishmaniasis of
      Mediterranean type from many years ago. This situation might cause to
      underestimate other important diseases, which occur sporadically within the same
      area. In this case, a 6-year-old male patient in this area was treated as
      infected with visceral leishmaniasis initially with seropositive result for
      visceral leishmaniasis. Afterwards, histopathological study of crashed material
      and tissue sections surprisingly revealed numerous liver fasciolid fluke eggs.
      This case demonstrates that in an area endemic for a given parasitoses, other
      important infectious diseases must be considered as well.

PMID- 23113033
TI  - Nutrigenomics and nutrigenetics.
AB  - The nutrients are able to interact with molecular mechanisms and modulate the
      physiological functions in the body. The Nutritional Genomics focuses on the
      interaction between bioactive food components and the genome, which includes
      Nutrigenetics and Nutrigenomics. The influence of nutrients on f genes expression
      is called Nutrigenomics, while the heterogeneous response of gene variants to
      nutrients, dietary components and developing nutraceticals is called
      Nutrigenetics. Genetic variation is known to affect food tolerances among human
      subpopulations and may also influence dietary requirements and raising the
      possibility of individualizing nutritional intake for optimal health and disease
      prevention on the basis of an individual's genome. Nutrigenomics provides a
      genetic understanding for how common dietary components affect the balance
      between health and disease by altering the expression and/or structure of an
      individual's genetic makeup. Nutrigenetics describes that the genetic profile
      have impact on the response of body to bioactive food components by influencing
      their absorption, metabolism, and site of action.In this way, considering
      different aspects of gene-nutrient interaction and designing appropriate diet for
      every specific genotype that optimize individual health, diagnosis and
      nutritional treatment of genome instability, we could prevent and control
      conversion of healthy phenotype to diseases.

PMID- 23113034
TI  - The development of a qualitative dynamic attribute value model for healthcare
      institutes.
AB  - BACKGROUND: Understanding customers has become an urgent topic for increasing
      competitiveness. The purpopse of the study was to develop a qualitative dynamic
      attribute value model which provides insight into the customers' value for
      healthcare institute managers by conducting the initial open-ended questionnaire
      survey to select participants purposefully. METHODS: A total number of 427
      questionnaires was conducted in two hospitals in Taiwan (one district hospital
      with 635 beds and one academic hospital with 2495 beds) and 419 questionnaires
      were received in nine weeks. Then, apply qualitative in-depth interviews to
      explore customers' perspective of values for building a model of partial
      differential equations. RESULTS: This study concludes nine categories of value,
      including cost, equipment, physician background, physicain care, environment,
      timing arrangement, relationship, brand image and additional value, to construct
      objective network for customer value and qualitative dynamic attribute value
      model where the network shows the value process of loyalty development via its
      effect on customer satisfaction, customer relationship, customer loyalty and
      healthcare service. CONCLUSION: One set predicts the customer relationship based
      on comminent, including service quality, communication and empahty. As the same
      time, customer loyalty based on trust, involves buzz marketing, brand and image.
      Customer value of the current instance is useful for traversing original customer
      attributes and identifing customers on different service share.

PMID- 23113035
TI  - Formaldehyde exposure and irritative effects on medical examiners, pathologic
      anatomy post-graduate students and technicians.
AB  - BACKGROUND: Exposure to formaldehyde (FA) causes irritative effects and induces
      nasopharyngeal cancer; the International Agency for Research on Cancer (IARC,
      Lyon) classified FA as carcinogenic to humans, Group 1. Many studies have been
      published so far concerning the occupational exposure of industrial workers,
      embalmers, pathologists and anatomists to FA but very few data regarding medical
      examiners are available. METHODS: To assess the extent to which subjects were
      exposed to FA, airborne concentrations of this chemical were measured by High
      Performance Liquid Chromatography (HPLC). In September-October 2006 we examined
      the personnel, which worked in an autopsy room (medical examiners) and in three
      laboratories of pathologic anatomy of the University Medical School of Bari,
      Policlinico Hospital, Southern Italy. Irritative effects were also investigated.
      RESULTS: All the personal exposure data obtained exceeded the National Institute
      for Occupational Safety and Health Threshold Limit Value-Time Weighted Average
      (NIOSH TLV-TWA: 0.02 mg/m(3)) and, in a few cases, even the American Conference
      of Industrial Hygienists Threshold Limit Value-Ceiling level (ACGIH TLV-C: 0.37
      mg/m(3)). CONCLUSION: Irritative effects in more than 50% of the workers
      enrolled, increasing the risk of injuries.

PMID- 23113036
TI  - Preliminary Identification and Typing of Pathogenic and Toxigenic Fusarium
      Species Using Restriction Digestion of ITS1-5.8S rDNA-ITS2 Region.
AB  - BACKGROUND: Fusarium species are capable of causing a wide range of crop plants
      infections as well as uncommon human infections. Many species of the genus
      produce mycotoxins, which are responsible for acute or chronic diseases in
      animals and humans. Identification of Fusaria to the species level is necessary
      for biological, epidemiological, pathological, and toxicological purposes. In
      this study, we undertook a computer-based analysis of ITS1-5.8SrDNA-ITS2 in 192
      GenBank sequences from 36 Fusarium species to achieve data for establishing a
      molecular method for specie-specific identification. METHODS: Sequence data and
      610 restriction enzymes were analyzed for choosing RFLP profiles, and
      subsequently designed and validated a PCR-restriction enzyme system for
      identification and typing of species. DNA extracted from 32 reference strains of
      16 species were amplified using ITS1 and ITS4 universal primers followed by
      sequencing and restriction enzyme digestion of PCR products. RESULTS: The
      following 3 restriction enzymes TasI, ItaI and CfoI provide the best
      discriminatory power. Using ITS1 and ITS4 primers a product of approximately
      550bp was observed for all Fusarium strains, as expected regarding the sequence
      analyses. After RFLP of the PCR products, some species were definitely identified
      by the method and some strains had different patterns in same species.
      CONCLUSION: Our profile has potential not only for identification of species, but
      also for genotyping of strains. On the other hand, some Fusarium species were
      100% identical in their ITS-5.8SrDNA-ITS2 sequences, therefore differentiation of
      these species is impossible regarding this target alone. ITS-PCR-RFLP method
      might be useful for preliminary differentiation and typing of most common
      Fusarium species.

PMID- 23113037
TI  - Specific PCR Assay for Rapid and Direct Detection of Neisseria meningitidis in
      Cerebrospinal Fluid Specimens.
AB  - BACKGROUND: Neisseria meninigitidis is one of the most frequently encountered
      microorganisms associated with central nervous system infections. The aim of this
      study was to evaluate a PCR-based assay for specific and rapid detection of N.
      meninigitidis in CSF specimens. METHODS: Since April 2002 to July 2006, 130 CSF
      specimens were collected from patients suspected of having bacterial meningitis.
      Bacterial isolation and identification was carried out according to the standard
      bacteriological methods. The PCR was used to amplify a 101bp fragment of capsular
      transport gene A (ctrA) of N. meningitidis. RESULTS: PCR yielded an amplified
      product with the expected size of 101 base pair fragment. Sensitivity test proved
      500 ng of N. meningitidis DNA as the final detection limit and specificity test
      revealed no cross-reaction for a wide range of respiratory pathogenic organisms.
      CONCLUSION: The PCR assay was more sensitive than the bacterial culturing. It
      might be possible to apply this procedure for rapid diagnosis of meningococci in
      clinical samples.

PMID- 23113038
TI  - The analysis of internet addiction scale using multivariate adaptive regression
      splines.
AB  - BACKGROUND: Determining real effects on internet dependency is too crucial with
      unbiased and robust statistical method. MARS is a new non-parametric method in
      use in the literature for parameter estimations of cause and effect based
      research. MARS can both obtain legible model curves and make unbiased parametric
      predictions. METHODS: In order to examine the performance of MARS, MARS findings
      will be compared to Classification and Regression Tree (C&RT) findings, which are
      considered in the literature to be efficient in revealing correlations between
      variables. The data set for the study is taken from "The Internet Addiction
      Scale" (IAS), which attempts to reveal addiction levels of individuals. The
      population of the study consists of 754 secondary school students (301 female,
      443 male students with 10 missing data). MARS 2.0 trial version is used for
      analysis by MARS method and C&RT analysis was done by SPSS. RESULTS: MARS
      obtained six base functions of the model. As a common result of these six
      functions, regression equation of the model was found. Over the predicted
      variable, MARS showed that the predictors of daily Internet-use time on average,
      the purpose of Internet-use, grade of students and occupations of mothers had a
      significant effect (P< 0.05). In this comparative study, MARS obtained different
      findings from C&RT in dependency level prediction. CONCLUSION: The fact that MARS
      revealed extent to which the variable, which was considered significant, changes
      the character of the model was observed in this study.

PMID- 23113039
TI  - Evaluation of a Single PCR Assays on Cp5 Gene for Differentiation of Entamoeba
      histolytica and E. dispar.
AB  - BACKGROUND: We examined a molecular method with a single-PCR for amplification of
      a part of CP5 gene enabling us to differentiate the pathogenic species, Entamoeba
      histolytica, from the non-pathogenic species, E. dispar. METHODS: We developed a
      single PCR method for this purpose. After investigation of GenBank, primer pairs
      were designed from highly conserved regions of cysteine proteinase (CP5) gene.
      The primers were utilized in PCR using isolated genomic DNA template of E.
      histolytica and the PCR products were then sequenced. The same primer and method
      for PCR was used for isolated genomic DNA template of E. dispar. RESULTS: A
      fragment of about 950 bp was isolated in PCR by using DNA from E. histolytica,
      however, no banding pattern was produced by using the same primers for E. dispar.
      We characterized CP5 gene at molecular level in E. histolytica isolates from 22
      positive; including 20 non-dysentery samples isolated from both cities as well as
      two dysentery samples isolated only from Tabriz. Nucleotide sequence comparison
      in gene data banks (NCBI, NIH) revealed significant homology with CP5 gene in E.
      histolytica isolates CONCLUSION: We developed a PCR method, which could detect
      simply and rapidly E. histolytica by amplifying a specific PCR fragment.

PMID- 23113040
TI  - Perceived health locus of control, self-esteem, and its relations to
      psychological well-being status in Iranian students.
AB  - BACKGROUND: Health locus of control (HLC) has been associated with a variety of
      ailments and health outcomes and designed to predict behaviors and cognitive
      processes relevant to mental and physical health. This study investigated the
      relationships between perceived health locus of control, self-esteem, and mental
      health status among Iranian students. METHODS: In this analytical study the
      subjects were recruited from students in Gonabad University of Medical Sciences,
      Iran, who studied in the first year (N=154). Students completed the
      questionnaires for assessing demographic, perceived health locus of control, self
      - esteem and psychological well- being data. RESULTS: The statistical analysis
      revealed a negative relationship between perceived Internal HLC and self-esteem
      with psychological well-being. The positive correlation of the perceived Chance
      HLC with psychological well-being was statistically significant (r= 0.21, P<
      0.01) and the positive correlation of the perceived Internal HLC with self-esteem
      was statistically significant (r= 0.25, P< 0.01). A significantly direct
      relationship between low perceived Internal HLC, self-esteem and psychological
      problems was found among these students. CONCLUSION: The findings will be
      addressed in relation to their implications for effective mental health education
      based on health locus of control especially internal and powerful others beliefs
      associated with self-esteem for students. This will require additional monitoring
      and uninterrupted trying in order to be effective.

PMID- 23113041
TI  - An analysis of anthropometric data on Iranian primary school children.
AB  - BACKGROUND: Anthropometric data can be used to identify the physical dimensions
      of equipment, furniture, etc. The use of furniture that fails to fulfill the
      anthropometric data of its users has a negative impact on human health. Specific
      anthropometric dimensions are necessary to design school furniture.
      Anthropometric data have been measured in many communities especially among
      schoolchildren. There are different ethnic groups with probably different
      anthropometric data in Iran, and anthropometric data can change by time, so
      gathering data about anthropometric dimensions is important. This study was
      designed to obtain anthropometric dimensions of Iranian children (Fars ethnicity)
      aged 7-11 years. METHODS: In a cross-sectional study in Yazd, Iran, descriptive
      statistics as well as key percentiles for 17 static anthropometric data of
      primary school students (1015 males and 1015 females), were measured and compared
      between boys and girls. RESULTS: The age of the students was between 6 and 11
      years. Mean weight was between 21.56+/-5.33 kg and 36.63+/-9.45 kg in boys and
      between 20.79+/-3.48 kg and 35.88+/-9.40 kg in girls. Mean height was between
      1187/02+/-53.98 mm and 1420.83+/- 69.39 mm in boys and between 1173.90+/-51.01mm
      and 1421.27+/-70.82 mm in girls. There was also some difference in other
      anthropometric data between two genders. CONCLUSION: Results of this study showed
      some differences in anthropometric data with other studies. We also observed
      significant gender differences in some dimensions as well.

PMID- 23113042
TI  - Health-related physical fitness and normative data in healthy women, tehran,
      iran.
AB  - BACKGROUND: The purpose of this study was to determine the age-related loss of
      health-related physical fitness and normative data in healthy population women
      aged 20-60 years old of Tehran, Iran. METHODS: In this cross-sectional study,
      1000 healthy women aged 20-60 years old were randomly selected from northern,
      southern, eastern, western and center regions of Tehran. Cardiovascular fitness
      was determined by Ros and Jakson protocol. Body composition were measured using
      Jackson and Poolak procedure, flexibility was determined by sit and reach test,
      muscular strength with a standard dynamometer and muscular endurance were
      measured with Sit-ups test in one minutes. RESULTS: Cardiovascular fitness
      (vo(2max)), body composition, flexibility, muscular strength and endurance
      remained unchanged in the 20 and 30 year old age groups. Around of 40 years old,
      cardiovascular fitness, muscular strength and endurance began to gradually
      decline but body composition increased and flexibility unchanged. Data for Vo2max
      and the other variables in 4-yr groups provide "normative" results. Result
      indicated age-related declined in Vo2max (0.43 ml/ kg/min* yr (-1)), muscular
      strength (0.004 kg/weight *yr (-1)) and endurance (0.63 repetition *yr (-1)), and
      increased in body fat (0.43 % *yr (-1)) in 30-60 year. One-way ANOVA test showed
      that all variables significantly differed (P<0.001) among decades except sit and
      rich test (P< 0.059) between the second and third decades. V(o2max) had a
      significant relationship (P< 0.01) with Age, BMI, body fat percent and muscular
      strength and endurance. CONCLUSION: Iranian women have a greater decline in
      cardiovascular fitness; muscular strength and endurance. The results of this
      study can be used as reference material for clinical studies in different age
      groups.

PMID- 23113043
TI  - Hospitals pharmacy quality assurance system assessment in tehran university of
      medical sciences, iran.
AB  - BACKGROUND: Health system pharmacies, like other health care professional,
      practice under a number of mandated standards. Basic concepts of quality
      assurance (QA) standards should be applied to hospital pharmacy practice. The
      survey reported here is to assess QA system implementation and its standard
      indicators observation in Tehran University of Medical Sciences (TUMS) hospitals'
      pharmacies in 2007 - 2008. METHODS: A cross - sectional, descriptive analytical
      survey was accomplished. First, a checklist within the framework of QA standard
      indicators was made to assess TUMS hospitals pharmacies practice. Collected data
      was saved by Excel software for recording and analyzed by SPSS version-15.
      Observation rate of QA standard indicators was classified by inappropriate,
      relatively appropriate, and appropriate. RESULTS: Characteristics of TUMS
      hospitals pharmacists organizational structure, size, equipment, safety facility
      and drug requirement were studied by QA standard indicators. CONCLUSION: Many of
      QA standard indicators are observed and implemented in TUMS hospitals pharmacies,
      but several of these standards are not observed too. It is appropriate that all
      TUMS hospitals pharmacies are required to advance the profession, often with the
      same goal of increasing involvement in direct patient care.

PMID- 23113044
TI  - The application of the health belief model in oral health education.
AB  - BACKGROUND: The goal of this study was to determine the application of health
      belief model in oral health education for 12-year-old children and its effect on
      oral health behaviors and indexes. METHODS: A quasi-experimental study was
      carried out on twelve-year-old girl students (n-291) in the first grade of
      secondary school, in the central district of Tehran, Iran. Research sample was
      selected by a multistage cluster sampling. The data was obtained by using a valid
      reliable questionnaire for measuring the perceptions, a checklist for observing
      the quality of brushing and dental flossing and health files and clinical
      observation. First, a descriptive study was applied to individual perceptions,
      oral behaviors, Oral Hygiene Index (OHI) and Decayed, Missing and Filled Teeth
      Index (DMFTI). Then an educational planning based on the results and Health
      Belief Model (HBM) was applied. The procedure was repeated after six months.
      RESULTS: After education, based on HBM, all the oral health perceptions increased
      (P<.05). Correct brushing and flossing are influenced by increased perceptions. A
      low correlation between the reduction of DMFTI and increased perceived severity
      and increased perceived barriers are found (r= -0.28, r = 0.43 respectively). In
      addition, there was a limited correlation between OHI and increased perceived
      benefits (r = -0.26). CONCLUSION: Using health belief model in oral health
      education for increasing the likelihood of taking preventive oral health
      behaviors is applicable.

PMID- 23113045
TI  - Backpack weight and musculoskeletal symptoms in secondary school students,
      tehran, iran.
AB  - BACKGROUND: Increased complaints by school students about back and shoulder pain
      and discomfort have raised concerns among parents, education professionals, and
      orthopedists and these discomforts may be because of schoolbag carriage. The aim
      of this study was to investigate of relationship of musculoskeletal symptoms with
      weight of backpack in Tehran secondary school students. METHODS: This cross
      sectional study was performed in the city of Tehran in 2009. Two hundred thirteen
      students participated in study. Nordic Musculoskeletal Questionnaire was used,
      asking about complaints of back, neck, and/or shoulders. Length and weight of the
      children were determined. Schoolbags were weighed, and the relative weight of the
      schoolbag was calculated. RESULTS: Most prevalent musculoskeletal discomfort was
      in shoulders as 38.1%, neck 27.6% and back 16.7%. Average difference of weight of
      backpack in sample that had musculoskeletal with other samples was significant
      (P< 0.05). CONCLUSION: Weight of the backpack appears to be strongly related to
      the occurrence of shoulder, neck, back, and extremities complaints in students.
      Although musculoskeletal discomforts are believed to be multifactorial in origin,
      the carriage and manipulating of heavy backpack is signally a suspected factor
      and may represent an overlooked daily physical stress for secondary students.

PMID- 23113046
TI  - The relation of body mass index and blood pressure in Iranian children and
      adolescents aged 7-18 years old.
AB  - BACKGROUND: The obesity and hypertension are the major risk factors of several
      life threatening diseases. The present study was aimed to investigate the
      relation between body mass index (BMI) the validated index of adiposity and
      different aspect of blood pressure (BP). METHODS: Systolic and diastolic blood
      pressures and also weight and height of 7 to 18 years old children and adolescent
      collected in 2002 and 2004 respectively. Data was consisted of 14865
      schoolchildren and adolescents from representative sample of country. BMI was
      classified according to CDC 2000 standards into normal (BMI<85th percentile), at
      risk of overweight (BMI>=85th and <95th percentile) and overweight (BMI>=95th
      percentile). Then, age-sex specific prevalence of being overweight was derived.
      ANOVA was used to investigate the effect of BMI on systolic blood pressure and
      diastolic blood pressure and mean arterial pressure of participants. RESULTS:
      Mean systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean
      arterial blood pressure (MAP) significantly increased with BMI (P< 0.0001) and
      age groups (P< 0.0001), and was significantly (P< 0.0001) higher in boys than
      girls especially in older ages. (P< 0.0001, interaction of age and BMI level).
      The proportion of being overweight was significantly higher in boys than girls
      was (7.4% vs. 3.6%; P< 0.0001). CONCLUSION: There is an association between BP
      and BMI in children and adolescence. SBP, DBP and MAP are associated with rise in
      BMI and age, which was lower in girls. This data can provide basics for public
      health policy makers and primary prevention policies in the country.

PMID- 23113047
TI  - Validation of a Persian Version of the Oral Health Impact Profile (OHIP-14).
AB  - BACKGROUND: The oral health-related quality of life indicators are increasingly
      used to measure the impact of the oral conditions on quality of life. One of the
      most used indicators is the Oral Health Impact Profile (OHIP-14), but it has
      never been applied in Iran. The aim of this study was to validate the usage of
      OHIP-14 among Iranians. METHODS: A cross-sectional study was performed in Kerman
      (Iran). A consecutive sample (n= 400) of the Kerman Dental School Clinics
      attending patients participated in this study. All participants self-completed
      the translated OHIP-14. Reliability analyses, validity tests, and responsiveness
      were carried out to evaluate the psychometric properties of the OHIP-14. RESULTS:
      The reliability coefficient (Cronbach's alpha) of the OHIP-14 was above the
      recommended 0.7 threshold and considered excellent (alpha: 0.85). The coefficient
      of the test-retest reliability measured by ICC was 0.88 (CI 95%: 0.80-0.93).
      Poorer oral condition was strongly associated with OHIP scores of the patients,
      supporting construct validity. Moreover, for evaluation of responsiveness, the ES
      was measured to be 0.43 and the SRM was 0.67. CONCLUSIONS: The Persian version of
      OHIP-14 is a precise, valid and reliable instrument for assessing oral health
      related quality of life among Persian population.

PMID- 23113048
TI  - First report of respiratory syncytial virus and human metapneumovirus co
      infection in a 2-year-old kawasaki patient in iran.
AB  - BACKGROUND: Respiratory virus infections in children are a leading cause of
      morbidity and mortality worldwide. METHODS: A total of 897 clinical specimens
      were collected from February 2007 to January 2008 and transported to the National
      Influenza Center. Two hundred and two samples belonged to children under the age
      of six from 897 specimens, described above, were selected. Then they were tested
      for influenza virus types and subtypes by real time PCR assay subsequently, the
      specimens were tested for RSV and hMPV by hemi-nested multiplex PCR and
      parainfluenza viruses type 1-4 by hemi-nested multiplex PCR and adenovirus by
      hemi-nested PCR. RESULTS: The throat swab was taken from the Kawasaki case with
      the history of chicken's contact. The specimen was tested for all influenza
      subtypes especially H5N1 and the results were negative. Meanwhile PCR was done
      for screening of other respiratory viruses that results came out positive for RSV
      and hMPV. CONCLUSION: In the present study, we demonstrated the possibility to
      detect dual infection caused by RSV and hMPV, but because of the extravagant
      pattern of this case, more investigation is suggested specially on Kawasaki
      patients.

PMID- 23113049
TI  - Genetic doping and health damages.
AB  - BACKGROUND: Use of genetic doping or gene transfer technology will be the newest
      and the lethal method of doping in future and have some unpleasant consequences
      for sports, athletes, and outcomes of competitions. The World Anti-Doping Agency
      (WADA) defines genetic doping as "the non-therapeutic use of genes, genetic
      elements, and/or cells that have the capacity to enhance athletic performance ".
      The purpose of this review is to consider genetic doping, health damages and
      risks of new genes if delivered in athletes. METHODS: This review, which is
      carried out by reviewing relevant publications, is primarily based on the
      journals available in GOOGLE, ELSEVIER, PUBMED in fields of genetic technology,
      and health using a combination of keywords (e.g., genetic doping, genes,
      exercise, performance, athletes) until July 2010. CONCLUSION: There are several
      genes related to sport performance and if they are used, they will have health
      risks and sever damages such as cancer, autoimmunization, and heart attack.

PMID- 23113050
TI  - The prevalence of honorary and ghost authorships in Iranian bio-medical journals
      and its associated factors.
AB  - BACKGROUND: The purpose of this study was to detect the prevalence of ghost and
      honorary authors and its determinant factors in bio-medical journals of Iran.
      METHODS: The study was done in 2009-10 in Tehran, Kerman, and Iran Medical
      Universities, Iran. We contacted the first or corresponding authors of the papers
      had published papers in the recent two issues of Iranian Journal of Public
      Health, Journal of Kerman University of Medical Sciences, and Tehran University
      Medical Journal. They explored the role of each coauthor and others who had done
      mouthing for the paper. Then, according to ICMJE criteria, we counted how many of
      them are real, honorary or ghost author. For the analysis, we utilized two
      databases. One included articles as the records and the other included authors as
      the records. RESULTS: From 124 articles, with 536 authors, 301 (56.1%) were
      honorary authors. Each article had 4.35 authors on average, while 2.4 of them
      were honorary authors. The percentage of honorary author in basic science
      articles was about 6% more than the articles of clinical sciences. Moreover, 89%
      of articles had at least one honorary author. About 20% of all articles had more
      than three honorary authors. Besides, 25 (21.43%) authors confessed they had
      colleague(s) omitted from the authors list, while only one (0.81%) of them met
      the authorship criteria. The percentage of agreement between the corresponding
      and the remaining authors on the number of honorary of the authors was about
      47.4% (Kappa= 0.27, P= 0.01). CONCLUSION: It seems that the present data might
      assist the authorities to make a decisive decision on amending the process of
      authorship in Iran.

PMID- 23113051
TI  - ExpIR-RO: A Collaborative International Project for Experimenting Voluntary
      Incident Reporting In the Public Healthcare Sector in Romania.
AB  - BACKGROUND: Patient safety within healthcare systems is a central aspect of
      health policy in most developed countries. From April 2007 to May 2009, the pilot
      project ExpIR-RO tested a voluntary incident reporting system in a public
      hospital in Bucharest Romania, in collaboration with two Italian hospitals (in
      Genoa and Milan). METHODS: Data were collected anonymously through a form based
      on the Australian Incident Monitoring System. After appropriate training in
      reporting adverse events (AEs), staff in the participating Departments
      voluntarily completed the form. The study lasted 12 months in the Bucharest and
      Genoa hospitals and 3 months in the Milan hospital. Frequency distributions of
      replies and AE rates per 1,000 hospitalization days per month were assessed.
      RESULTS: Overall, 185 AEs were reported (58 in Bucharest, 75 in Genoa and 52 in
      Milan). The corresponding rates (per 1,000 hospitalization days per month) were 1
      in Bucharest, 3 in Genoa and 15 in Milan. Most AEs were related to diagnostic
      (28%) and surgical (14%) procedures and patient falls (12%) in Bucharest; patient
      falls (32%), nursing care (20%) and diagnostic procedures (19%) in Genoa; and
      nursing care (25%), drug prescription/administration (21%) and diagnostic
      procedures (17%) in Milan. Seventy-three per cent of respondents in Bucharest
      informed the patient of the AE, versus 64% in Genoa and 43% in Milan. Conversely,
      75% of respondents in Genoa entered AEs in medical records versus 53% in
      Bucharest and 36% in Milan. CONCLUSION: ExpIR-RO experience suggests that
      incident reporting could be introduced on a larger scale in Romania.

PMID- 23113052
TI  - The Blame Game: Stigma and HIV/AIDS in an African Metropolis.
AB  - BACKGROUND: The purpose of the present study was to explore further the cross
      cultural validity, consistency, and replicability of FAIDSS among students when
      assessing HIV/AIDS-related stigma and fear of people living with HIV/AIDS (PLWHA)
      in Lagos metropolis. METHODS: Using a purposive method, participants in Lagos
      Metropolis were surveyed using a questionnaire and conceptualization derived from
      the work of Ross and Hunter (1992) to measure a variety of HIV-related
      attitudinal and behavioural items. Quantitative data analyzed employing factor
      analysis using maximum-likelihood extraction followed by oblique rotation (direct
      oblimin, delta= 0). RESULTS: On the factor scale measuring having fear of sex
      with a particular person, younger respondents especially females significantly
      more likely to report greater fear than for any other groups. Our findings
      further suggest that levels of fear of outsiders are high among males and need
      urgent action and intervention at both individual and societal levels.
      CONCLUSION: It is argued that messages and interventions must be targeted to
      promote a positive social environment for those living with or affected by
      HIV/AIDS, and to be useful in understanding stigma, fear and prejudice more fully
      and in reducing them. A crosscurrent behavioral change that can transform AIDS
      from an inevitably fatal pandemic to a chronic and manageable disease is the
      answer.

PMID- 23113053
TI  - Molecular Epidemiology of Measles Virus before and after the 2003 Mass
      Vaccination Campaign for Measles/Rubella in Iran.
AB  - BACKGROUND: Molecular epidemiology of measles virus (MV) is important, not only
      to measure the success of measles vaccination programs but also to monitor the
      circulation and elimination of the virus worldwide. In this study, we compared MV
      obtained from patients before the 2003 mass vaccination MR campaign and viruses
      detected after 2003 until 2008 in Iran. METHODS: The nucleoprotein (N) gene of 29
      MV strains circulating in Iran between 2002 and 2008 were amplified by RT-PCR and
      subjected to sequence and phylogenetic analysis. RESULTS: Molecular
      characterization of MV studied here revealed that although the outbreaks in Iran
      were associated with MV genotype D4, the isolated viruses clearly belonged to
      several different lineages. Maximum and minimum homology within the 29 Iranian
      strains in our study was100% and 94.9% within the carboxyl terminus of the N
      gene, respectively. Using ClustalX program, the alignment of Iranian MV sequences
      showed nine lineages. CONCLUSION: This study provides the usefulness of MV
      sequence analysis for the demonstration of local interruption of indigenous
      strain transmission as well as providing a valuable means for monitoring the
      elimination processes of MV control.

PMID- 23113054
TI  - A Pilot Study Evaluating the Stigma and Public Perception about the Causes of
      Depression and Schizophrenia.
AB  - BACKGROUND: To evaluate public perceptions towards the causes of depression and
      schizophrenia and identifications of factors resulting stigma towards mental ill.
      METHOD: A cross-sectional study was conducted among the inhabitants of Pulau
      Pinang, Malaysia in March, 2009. A 24-item questionnaire was used to obtain
      respondent views. A non-probability (i.e convenient sampling method) was used to
      approach the potential respondents. Data analysis was conducted using SPSS
      version 13 (r), non-parametric statistics (Chi-square) was applied to determine
      the association. Alpha value less than 0.05 were considered significant. RESULTS:
      One hundred respondents showed their willingness to participate in the study;
      overall response of the study was 40.0%. Majority 69% of the respondents were
      Malays, followed by Chinese and Indians. Public recognition toward depression was
      higher than schizophrenia. Lack of social support (X(2)= 4.832, P= 0.049),
      chemical imbalance in Brian (X(2)=6.132, P= 0.013*) and believes in supernatural
      factors (X(2)= 6.700, P= 0.050) were the commonly shared reasons for the mental
      disorders. Evaluation in terms of stigma revealed that majority 61 (55.0%).
      Individuals with mental disorders were not friendly (X(2)= 1.008, P= 0.050).
      Furthermore, one third of the population believe that they are moody, dangerous
      and unpredictable, it is better to avoid them. CONCLUSION: Overall findings
      revealed that Malaysians believe in supernatural reasons for the prevalence of
      mental disorders. Similarly the level of stigma towards mentally ill was higher
      among the respondents.

PMID- 23113055
TI  - An Experience of Peer Education Model among Medical Science University Students
      in Iran.
AB  - BACKGROUND: The purpose of this study was to evaluate the effectiveness of peer
      education among university students for reproductive health promotion based on
      researchers' experiences. METHODS: This interventional study was conducted in
      Qazvin University of Medical Science during 2002 to 2004 through stakeholders'
      partnership and selection of 24 volunteer students according to their knowledge,
      interest, communication skills. Capacity building was performed through holding
      an interactive reproductive health coarse contained marital health, illegal
      abortion, family planning, STI/AIDS, communication and counseling skills. Trained
      peer educators have introduced to other student and present education and
      counseling formally and informally. A post interventional study was conducted
      after 9 months in order to find its effectiveness. RESULTS: In our experience
      Stakeholders' partnership in community interventional programs led to the best
      expected availability of better health through ownership and adopting policies.
      In present study, the proper determined criteria for selection of peer educators
      and clear understood expectations of the peer educators' role were very important
      in health promotional program. Although peer education was acceptable program for
      university students, more support and supervising for peer groups are needed. The
      students believed that the power point of peer education and counseling related
      to same age groups sympathy, confident, well behaved, cheerful, and kind-hearted
      and peer educators awareness. CONCLUSION: Universities are appropriate real world
      for experience a friendly youth program and then disseminate it to other young
      communities. There seems peer education is effective strategy for reproductive
      health promotion and reinforce positive behaviors in youth.

PMID- 23113056
TI  - Seroprevalence and Coinfections of Toxoplasma gondii in Childbearing Age Women in
      Turkey.
AB  - BACKGROUND: Our aim was to detect the rate of Toxoplasma gondii infections and
      the coinfections in childbearing age women in Turkey accompanying using
      seroprevalence data from a multicenter hospital setting. METHODS: Overal, 17751
      childbearing age women through 16-45 years were included to the study between
      2004 and 2010. The clinical samples of the patients were collected from 16
      hospitals and medical centers mostly from Istanbul and three other cities from
      Turkey. Enzyme immunoassay tests were performed in our central laboratory in
      Istanbul to investigate T. gondii with other TORCH infections or Epstein Barr
      virus, Hepatitis B virus, Hepatitis C virus and Human Immunodificiency virus as
      accompanying infections. RESULTS: Among the tested sera 1.34% of the women were
      IgM and 24.61% were IgG positive for T. gondii. The coinfection rate was 3.36%
      among the IgM positive patients. CMV, EBV, HCV and rubella were detected as
      coinfections. IgM seropositivities of those infection agents were accepted as
      acute infection. CMV and EBV were detected as 1.26% and HCV and rubella were
      detected as 0.42%. CONCLUSION: Turkish female population was found infected with
      T. gondii in high rates. Some of the seropositive patients also had accompanying
      CMV, EBV, HCV and rubella infections. Our aim was to detect Toxoplasma
      seropositivity and the accompanying infections with their rates. While
      coinfections worsen the situation unless they are detected, it is important to
      determine exact situation of the patient for the management of the therapy.

PMID- 23113057
TI  - Microtitration of rubella virus in monovalent vaccinal products.
AB  - BACKGROUND: Potency test for control of rubella vaccine is a significant factor
      to qualify production line and vaccination program. For this reason, WHO
      recommends to use the microtitration method by both vaccine companies and control
      laboratories. Then the study was done to improve this test. METHODS: Three
      rubella virus samples, including an in-house standard, a lot of vaccine and an in
      process product, were tittered in cell culture tubes. Then micro titration steps
      were tested on 96-well microplate using cocultivation of standard rubella vaccine
      dilutions and RK-13 cell line. After 6-7 days, final reading was done and
      calculated the titer. Two other samples were assayed with the micromethod.
      RESULTS: Titer reduction less than 0.5 log was acquired for each sample during
      frequent tests and between two methods. CONCLUSION: The procedure was profitable
      and accurate for potency and identity tests of rubella virus vaccine, on the
      basis of WHO recommendations.

PMID- 23113058
TI  - Examining the Relationship between Psychosocial Work Factors and Musculoskeletal
      Discomfort among Computer Users in Malaysia.
AB  - BACKGROUND: With computers rapidly carving a niche in virtually every nook and
      crevice of today's fast-paced society, musculoskeletal disorders are becoming
      more prevalent among computer users, which comprise a wide spectrum of the
      Malaysian population, including office workers. While extant literature depicts
      extensive research on musculoskeletal disorders in general, the five dimensions
      of psychosocial work factors (job demands, job contentment, job control, computer
      related problems and social interaction) attributed to work-related
      musculoskeletal disorders have been neglected. This study examines the
      aforementioned elements in detail, pertaining to their relationship with
      musculoskeletal disorders, focusing in particular, on 120 office workers at
      Malaysian public sector organizations, whose jobs require intensive computer
      usage. METHODS: Research was conducted between March and July 2009 in public
      service organizations in Malaysia. This study was conducted via a survey
      utilizing self-complete questionnaires and diary. The relationship between
      psychosocial work factors and musculoskeletal discomfort was ascertained through
      regression analyses, which revealed that some factors were more important than
      others were. RESULTS: The results indicate a significant relationship among
      psychosocial work factors and musculoskeletal discomfort among computer users.
      Several of these factors such as job control, computer-related problem and social
      interaction of psychosocial work factors are found to be more important than
      others in musculoskeletal discomfort. CONCLUSION: With computer usage on the rise
      among users, the prevalence of musculoskeletal discomfort could lead to
      unnecessary disabilities, hence, the vital need for greater attention to be given
      on this aspect in the work place, to alleviate to some extent, potential problems
      in future.

PMID- 23113059
TI  - Enteric protozoan parasites in rural areas of bandar-abbas, southern iran:
      comparison of past and present situation.
AB  - BACKGROUND: The main goal was to address the prevalence of enteric protozoan
      parasites in rural areas of Bandar-Abbas, southern Iran and to compare the
      results with the only conducted study in 1978. METHODS: This descriptive study
      was performed from 2009 through 2010 on the 565 fecal samples. Formalin-ether
      concentration technique was performed and the analysis was carried out using Chi
      square test in SPSS software version 13.5. Finally, the comparison of our results
      with the only previous study which was accomplished by Sheiban and Rezaeian in
      1978 was done. RESULTS: The overall prevalence of the protozoan parasites was
      48.8%. However, the prevalence of pathogen parasites was 23%. Previous research
      in 1978 showed 80.4% infectivity. The most protozoan parasites were Blastocystis
      hominis (25.53%), Giardia lamblia (17.2%) and Entamoeba coli (15.95%). Previous
      study in 1978 found Entamoeba coli as the most common protozoa. Our finding
      revealed that the rate of single infectivity was much higher compared to previous
      research. The most frequency of infection was in children. CONCLUSION: The
      remarkable decrease of protozoan parasites is mainly due to progress in health
      care in the villages; however more effort should be done with the goal of
      eradicating infectious agents.

PMID- 23113061
TI  - Household catastrophic health expenditure.
AB  - BACKGROUND: Fairness in financial contribution for health was determined by WHO
      (World Health Report, 2000) as the third goal of health systems which is measured
      by fairness in financial contribution index (FFCI). The aim of this study was to
      estimate FFCI and quantify extent of catastrophic household heath expenditures.
      METHODS: We conducted a descriptive study during May 2008. Subjects were chosen
      by "Systematic Random sampling" among residents of Maskan's population-based
      research center (Maskan Center) in Kermanshah, Iran. After completing informed
      consent form, we collected data using a questionnaire by interview with head of
      family. In order to describing data and estimating FFCI, we used descriptive
      statistics and WHO methodology, respectively. Households with catastrophic
      expenditures and impoverished households were defined as those with health
      expenditures over 40% and 50% of their ability to pay, respectively. RESULTS: The
      mean age of head of families was 48.96+/-12.86 years. From 189; 12.7% of
      household's heads were female. 75.1% of households were covered by at least one
      health insurance scheme. FFCI was 0.57. The proportion of households facing
      catastrophic health expenditures was 22.2% (95% CI=16.3%-28.1%) CONCLUSION: The
      rate of FFCI among participants implied an inequality in health financing
      contribution. In addition, many of households (22.2%) faced catastrophic health
      expenditures while according to WHO estimation, the figure in the whole country
      was 2% in 1999. Our study revealed the importance of protecting households
      against the costs of ill-health.

PMID- 23113060
TI  - Association of physical activity with risk of type 2 diabetes.
AB  - BACKGROUND: Physical activity has shown to prevent type diabetes 2. However, the
      type, intensity and amount of effective physical activity as well as individuals'
      needs according to level of their risk for type 2 diabetes have not been
      clarified comprehensively. This study investigated a relation between moderate
      aerobic physical activity >=150 minuets/week with decreased risk of type 2
      diabetes among obese and non-obese residents of south of Tehran, Iran. METHODS:
      This study, which was a part of the Cardiovascular Risk Factors Survey in Tehran
      population Lab region, was designed and conducted based on MONICA/WHO project.
      Totally, 1552 adult inhabitants of 17th district of Tehran were enrolled in this
      cross-sectional study. Physical activity was assessed by MONICA Optional Study of
      Physical Activity questionnaire. Diabetes was defined as a history of a prior
      diagnosis of diabetes or fasting serum glucose >=126 mg/dl. All data analyses
      were conducted using SPSS 17 software for Windows RESULTS: In a multivariate
      model, moderate aerobic physical activity >=150 minuets/week was significantly
      associated with decreased risk of type 2 diabetes in all and non-obese subjects
      [OR= 0.56; 95%CI: 0.35-0.91 and OR= 0.50; 95%CI: 0.26-0.94, respectively]. There
      was no significant relation between the physical activity and type 2 diabetes
      risk in obese subjects [OR=0.64; 95%CI: 0.30-1.39]. CONCLUSION: Moderate aerobic
      physical activity >=150 minuets/week was significantly associated with decreased
      risk of type 2 diabetes in non-obese people and could be an acceptable exercise
      goal for these individuals. However, obese people should be investigated more to
      produce a tailored exercise guideline to this population at high risk of type 2
      diabetes.

PMID- 23113062
TI  - Pulmonary Tuberculosis in Patients with HIV/AIDS in Iran.
AB  - BACKGROUND: Pulmonary tuberculosis is still the most common form of tuberculosis
      in HIV infected patients having different presentations according to the degree
      of immunosuppression. This study appraised the impact of HIV infection on
      clinical, laboratory and radiological presentations of tuberculosis. METHODS: The
      clinical, laboratory and radiological presentations of pulmonary TB in 56 HIV
      infected patients were compared with 56 individually sex and age matched HIV
      seronegative ones, admitted to Imam Hospital in Tehran (1999-2006) using paired t
      test in a case control study. RESULTS: All cases and the controls were male.
      Fever was found in 83.9% of the HIV positive patients compared to 80% of the HIV
      negative ones. Cough was the most common clinical finding in the HIV negative
      group (89.3% vs. 82.1% in HIV positive group). Among radiological features,
      cavitary lesions, upper lobe and bilateral pulmonary involvement were observed
      significantly less often in the HIV-infected group. On the contrary,
      lymphadenopathy was just present in the HIV positive group in this series of
      patients (12%) and primary pattern tuberculosis was more common, as well (71% vs.
      39%, P= 0.02). The Tuberculin test was reactive in 29% of the HIV/TB patients.
      CONCLUSION: The coexistence of both infections alters the picture of tuberculosis
      in many aspects and should be taken into account when considering a diagnosis of
      HIV infection and its potential for TB co-infection, and vice-versa.

PMID- 23113063
TI  - Detection of Leptospires serogroups, Which Are Common Causes of Human Acute
      Leptospirosis in Guilan, Northern Iran.
AB  - BACKGROUND: This study is performed to reveal most common species and subspecies
      of leptospires that are main causes of human leptospirosis in Guilan, Northern
      Province of Iran. METHODS: We performed IgM-ELISA and MAT on 282 blood samples
      from patients who attended to 3 hospitals in the flat area of Guilan Province
      with clinical symptoms consisted with leptospirosis. All specimens with titers >=
      160 against at least one pathogenic strain in MAT and with titers >=160 in IgM
      ELISA were regarded confirmed positive cases indicative acute disease. For any
      confirmed positive cases, we determined the strains, which had the highest titer
      to determine the frequency of most common serovars and serogroups. RESULTS:
      Seventy of 282 sera had titers >=160 against at least one pathogenic strain in
      MAT and titers >= 160 in IgM-ELISA. We determined frequency of common causative
      serogroups which had highest titers in 70 positive cases and only cases which had
      high titers in MAT and in IgM-ELISA were selected which is a reliable criterion
      to detect acute disease and to determine causative serogroup. CONCLUSION: Nine
      serogroups including sejroe, grippotyphosa, mini, ictero haemorrhagiae,
      celledoni, autumnalis, cynopteri, pomona, and javanica were more responsible of
      acute leptospirosis in Guilan.

PMID- 23113064
TI  - Aflatoxin M1 in Pasteurized Milk in Babol city, Mazandaran Province, Iran.
AB  - BACKGROUND: Aflatoxin M(1) (AFM(1)) is the metabolite of aflatoxin B1 (AFB(1))
      and is found in milk when lactating animals are fed with contaminated feedstuff.
      The presence of AFM(1) in milk, pose a major risk for humans especially kids as
      it can have immunosuppressive, mutagenic, teratogenic and carcinogenic effects.
      The present study is aimed to investigate the occurrence of AFM(1) in subsidized
      pasteurized milk in Babol, Mazandaran Province, Iran. METHODS: Some 72
      pasteurized milk packages were collected from supermarkets in various districts
      of city during January to March 2006. Milk samples were centrifuged and amounts
      of 100 MUl of skimmed milk were tested for AFM(1) contamination by competitive
      ELISA. RESULTS: All the samples (100%) exhibited contamination with AFM(1). The
      contamination levels means in January, February, and March were 227.85, 229.64,
      and 233.1ng/l, respectively. The amount of AFM(1) in all the samples were above
      50ng/l, the threshold set by the European community regulations. CONCLUSION:
      Monitoring of AFM(1) level should be part of quality control procedures in dairy
      factories, particularly the ones providing infant's milk. Production of safer and
      healthier milk and other dairy products with minimum AFM(1) level can be achieved
      by adopting prophylactic measures including control of humidity and water content
      of feedstuff, which favors mould production.

PMID- 23113065
TI  - Iranian Azeri's Y-Chromosomal Diversity in the Context of Turkish-Speaking
      Populations of the Middle East.
AB  - BACKGROUND: The main goal of this study was to conduct a comparative population
      genetic study of Turkish speaking Iranian Azeries as being the biggest ethno
      linguistic community, based on the polymorph markers on Y chromosome. METHODS:
      One hundred Turkish-speaking Azeri males from north-west Iran (Tabriz, 2008-2009)
      were selected based on living 3 generations paternally in the same region and not
      having any relationship with each other. Samples were collected by mouth swabs,
      DNA extracted and multiplex PCR done, then 12 Single Nucleotide Polymorphisms
      (SNPs) and 6 Microsatellites (MS) were sequenced. Obtained data were
      statistically analyzed by Arlequin software. RESULTS: SNPs and Microsatellites
      typing were compared with neighboring Turkish-speaking populations (from Turkey
      and Azerbaijan) and Turkmens representing a possible source group who imposed the
      Turkish language during 11-15(th) centuries AD. Azeris demonstrated high level of
      gene diversity compatible with patterns registered in the neighboring Turkish
      speaking populations, whereas the Turkmens displayed significantly lower level of
      genetic variation. This rate of genetic affiliation depends primarily on the
      geographic proximity. CONCLUSION: The imposition of Turkish language to this
      region was realized predominantly by the process of elite dominance, i.e. by the
      limited number of invaders who left only weak patrilineal genetic trace in modern
      populations of the region.

PMID- 23113067
TI  - Genetic Association Analysis of Dopamine DRD3 Ser9Gly Polymorphism and
      Schizophrenia in Malay Population.
AB  - BACKGROUND: Molecular components of the dopamine receptor (DRD3) play an
      important role in the pathophysiology of schizophrenia (SCZ). Previous studies
      have demonstrated an association between the DRD3 Ser9Gly polymorphism and SCZ
      but the results have been inconclusive. METHOD: In this study, we investigated
      this controversial association between the Ser9Gly (A/G) polymorphism and SCZ
      using Malay cases-control (261 cases/157 controls) samples. PCR-RFLP was
      performed to genotype the distribution of the DRD3 Ser9Gly polymorphism. RESULTS:
      Both healthy control and SCHZ patient groups were in of Hardy-Weinberg
      equilibrium for the analyzed genetic variability. There was a significant
      association between the genotype distribution DRD3 polymorphisms and SCZ (chi(2)=
      9.359; df = 2; P = 0.009). CONCLUSION: We believe that further studies are
      required to examine the association between others dopamine-related genes and the
      behavioral phenotypes of SCZ.

PMID- 23113066
TI  - Association between Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)
      and Components of Metabolic Syndrome in Young Chinese Men.
AB  - BACKGROUND: To investigate the prevalence of metabolic syndrome (MetS) in young
      Chinese population and assess the association between HOMA-IR and different
      components of MetS in young Chinese men. METHODS: Overall 5576 young Chinese
      subjects (age range [19-44 yr], 3636 men) were enrolled in, who visited our
      Health Care Center for a related health checkup from March to December 2008. The
      international diabetes federation (IDF) definition for MetS was used. The SPSS
      statistical package, version 11.5 was used for the statistical analysis. RESULTS:
      The prevalence of MetS was 21.81% in young men and 5.62% in young women.
      According to suffering from different numbers of MetS components, the male
      subjects were divided into four groups. Numbers of MetS components were more and
      HOMA-IR values were significantly higher. In this male population, the quartile
      of HOMA-IR was higher, values of triglyceride (TG), fasting plasma glucose (FBG),
      systolic blood pressure(SBP), diastolic blood pressure(DBP) and waist
      circumference (WC) were all significantly higher, as well as high density
      lipoprotein cholesterol (HDL-C) value was significantly lower (P= 0.000). In
      Spearman's correlation analysis, HOMA-IR was positively correlated with TG, FBG,
      SBP, DBP and WC, and negatively correlated with HDL-C (r= 0.460, 0.464, 0.362,
      0.346, 0.586, -0.357, respectively, all P value= 0.000). CONCLUSION: The
      prevalence of MetS in these young Chinese men was obviously high. Insulin
      resistance played an important role in occurrence and development of MetS. Waist
      circumference was the best correlation with HOMA-IR among all components of MetS.

PMID- 23113068
TI  - Breastfeeding practices in infants in the west region of cameroon.
AB  - BACKGROUND: The study was conducted to evaluate the knowledge, attitudes and
      practices of breast-feeding in the West region of Cameroon. METHODS: A cross
      sectional descriptive study was conducted in two health facilities on 195 mother
      infant pairs, seen at the out patient and vaccination units of the Bafoussam
      Regional Hospital over a period of one month from 1(st) to 30(th) September 2008.
      The socio-demographic characteristics of mothers, knowledge on breastfeeding and
      the practice of breastfeeding were studied. Data was analyzed using the SPSS
      software. The chi square and student t- test were used for comparison and results
      considered significant for P< 0.05. RESULTS: Breastfeeding was practised by
      99.48% of the mothers. Only 33.8% of the mothers knew that they had to
      exclusively breastfeed up to 6 months, and 20% effectively breastfed up to 6
      months. The mean duration of breastfeeding was 5.06 months and negatively
      correlated with the number of children and the profession of the mother. In
      69.74% of the women, nothing was given to the baby before the first breastfeed.
      Discontinuation of breastfeeding was done averagely around 15.24 months and
      earlier in married women and in those with a higher educational level.
      CONCLUSION: Although the majority of parents practised breast feeding, only a
      minority understood its benefits, so more should be done to educate the community
      on the benefits of exclusive breast-feeding for up to six months.

PMID- 23113069
TI  - Association between Anthropometric Measures and Bone Mineral Density: Population
      Based Study.
AB  - BACKGROUND: Osteoporosis is a major public health concern around the world. It
      has been shown that bone mineral density is correlated to anthropometric measures
      like height and weight, but this association may vary depending on ethnic and
      environmental factors. The aim of this study was to identify probable relations
      between anthropometric measures and bone mineral density. METHODS: In this
      population-based study, we compiled the data collected from Iranian Multicenter
      Osteoporosis Study to assess the possible associations between different
      anthropometric indices and bone mineral density at femur and lumbar spine. The
      gathered data was analyzed using t-test and one way ANOVA. RESULTS: Data was
      available for 4445 subjects, consisting 1900 males (42.7%) and 2545 females
      (57.3%). We observed statistically significant correlations between bone mineral
      density and height, weight, waist circumference, hip circumference, waist to hip
      ratio and body mass index (BMI). Based on the result of linear regression
      modeling studies, BMI could be considered an independent predictor of bone
      mineral density. CONCLUSION: Iranian population shows similar measures compared
      to analogous studies in other populations. Lower weight should be carefully
      considered as a predisposing factor for bone loss and osteoporosis.

PMID- 23113070
TI  - The assessment of inequality on geographical distribution of non-cardiac
      intensive care beds in iran.
AB  - BACKGROUND: The purpose of the present study was to evaluate the inequality of
      geographical distribution of non-cardiac intensive care beds in Iran using the
      Gini coefficient. METHODS: The population information of Iran's provinces in 2006
      was obtained from The Statistical Center of Iran and the number of non-cardiac
      intensive care beds (including ICU, PostICU and NICU beds) in all provinces was
      taken from published information of Ministry of Health and Medical Education of
      Iran in the current year. The number of beds per 100,000 populations of each
      province and the Gini coefficients for each bed were calculated. RESULTS: Iran's
      population was 70,495,782. The total number of ICU, PostICU and NICU beds were
      3720, 291 and 1129, respectively. Tehran had the highest percentage of each bed
      among all provinces. The number of each bed was 5.3, 0.4 and 1.6 per 100,000
      populations of country, respectively. The calculated Gini coefficients for each
      bed were 0.17, 0.15 and 0.23, respectively. CONCLUSION: The findings of this
      study showed that, according to the Gini coefficients, non-cardiac intensive care
      beds have an almost equal geographical distribution throughout the country.
      However, the numbers of beds per population are less than other countries. Since
      such studies can be used as a base for health systems planning about correction
      of inequality of health services distribution, similar studies in other health
      care services are recommended which can be conducted at the national or
      provincial level.

PMID- 23113071
TI  - Genetic Linkage Analysis of 15 DFNB Loci in a Group of Iranian Families with
      Autosomal Recessive Hearing Loss.
AB  - BACKGROUND: Hearing loss (HL) is the most frequent sensory birth defect in
      humans. Autosomal recessive non-syndromic HL (ARNSHL) is the most common type of
      hereditary HL. It is extremely heterogeneous and over 70 loci (known as DFNB)
      have been identified. This study was launched to determine the relative
      contribution of more frequent loci in a cohort of ARNSHL families. METHODS:
      Thirty-seven Iranian families including 36 ARNSHL families and 1 family with
      Pendred syndrome each with >= 4 affected individuals, from seven provinces of
      Iran, were ascertained. DFNB1 contribution was initially studied by DNA
      sequencing of GJB2 and linkage analysis using the relative STR markers. The
      excluded families were then subjected to homozygosity mapping for fifteen ARNSHL
      loci. RESULTS: Sixteen families were found to be linked to seven different known
      loci, including DFNB1 (6 families), DFNB4 (3 families +1 family with Pendred
      syndrome), DFNB63 (2 families), DFNB2 (1 family), DFNB7/11 (1 family), DFNB9 (1
      family) and DFNB21 (1 family). DNA sequencing of the corresponding genes is in
      progress to identify the pathogenic mutations. CONCLUSION: The genetic causes
      were clarified in 43.2% of the studied families, giving an overview of the causes
      of ARNSHL in Iran. DFNB4 is ranked second after DFNB1 in the studied cohort. More
      genetic and epigenetic investigations will have to be done to reveal the causes
      in the remaining families.

PMID- 23113072
TI  - Cutaneous leishmaniasis in bam: a comparative evaluation of pre- and post
      earthquake years (1999-2008).
AB  - BACKGROUND: The recent devastating earthquake of December 26 in Bam, 2003 created
      various risk factors; caused a sharp increase in incidence of anthroponotic
      cutaneous leishmaniasis (ACL) cases and reached to an epidemic proportion. The
      objective of this study was to evaluate the status of ACL cases five years before
      the earthquake compared to the cases occurred five years after the earthquake
      (1999-2008). METHODS: Status of disease was assessed retrospectively for the five
      years before the earthquake and prospectively for the five years after the
      earthquake. Identification was confirmed by smear and polymerase chain reaction
      (PCR). RESULTS: The mean annual incidence of ACL for the period from 1999 to 2003
      was 1.9 per 1000 comparing to post earthquake period, which was 7.6 per 1000.
      Most of the infection was in individuals of <20 years, more frequently in females
      before the earthquake, whilst in contrast, there was a progressive rise in the
      number of cases, significantly in male individuals of >20 years (P< 0.0001) in
      post earthquake era. The anatomical distribution of lesions considerably changed
      during the two periods. Most of the cases were limited to three zones within the
      city prior to the earthquake, whereas it was spread throughout different zones
      after the earthquake. PCR indicated that the CL was due to Leishmania tropica in
      the city. CONCLUSION: The results strongly suggest that in natural disasters such
      as earthquakes various precipitating factors in favor of disease will be created,
      which in turn provide a suitable condition for propagation of the vector and the
      transmission of the parasite.

PMID- 23113073
TI  - Sequence Variants of BRCA1 and BRCA2 Genes in Four Iranian Families with Breast
      and Ovarian Cancer.
AB  - BACKGROUND: BRCA1 and BRCA2 genes have been recognized to be responsible for 20
      30% of hereditary breast cancers and approximately 50% of familial breast and
      ovarian cancers. Therefore, the demand for BRCA1 and BRCA2 mutation screening is
      rapidly increasing as their identification will affect medical management of
      people at increased risk. Because of high costs involved in analysis of BRCA1 and
      2 genes, contribution of different mutation types in BRCA1 and 2 and not knowing
      who should be tested has hampered wide spread use of molecular testing of high 
      risk families. There is a need to identify the genes and types of mutations
      involved in breast or ovarian cancers at different age of onsets and polymorphism
      and polymorphic variations in our population. METHODS: Twenty-seven patients with
      either early onset breast cancer (at age<= 35 years) or a personal and/or family
      history of breast or ovarian cancer and 50 control subjects participated in this
      study. After collecting blood samples and extracting DNA, BRCA1 and BRCA2 genes
      were fully sequenced. RESULTS: Thirteen missense substitutions in BRCA1 and BRCA2
      (9 and 4, respectively) were revealed. Two nucleotide substitutions were novel
      (Gly1140Ser in BRCA1 and Glu1391Gly in BRCA2). The Glu1038Pro and Gly1140Ser were
      found in large series of breast and ovarian cancer and matched controls.
      CONCLUSION: Some nucleotide substitutions were seen only in single families and
      other in several. In other cases, mutations were seen in both BRCA1 and BRCA2
      genes. Clinical significance of these mutations was evaluated comparing with
      normal controls.

PMID- 23113074
TI  - Association between Malnutrition and Depression in Elderly People in Razavi
      Khorasan: A Population Based-Study in Iran.
AB  - BACKGROUND: To determine the prevalence of malnutrition and depression in free
      living elderly people and their relationships (If any) in Razavi Khorasan, Iran
      2007. METHODS: To evaluate nutritional status, we used Mini Nutritional
      Assessment (MNA) method in free-living elderly people (n=1565 using cluster
      sampling, 720 males and 845 females, aged>= 60 yr) and their relationship to
      Socio Economic Conditions (SECs). Based on the final scores, our patients were
      classified into three groups: score 17-23.5 (at risk for malnutrition), score
      less than 17 (with malnutrition), and score 24-30 (well nourished). To determine
      the mood status (here depression), we used Geriatric Depression Score (GDS).
      According to this score our participants turned out to be in two distinct groups:
      depressed (score >=8) and non-depressed (score < 8). RESULTS: From the total
      subjects entered the study (1495), 22.07% were depressed and 11.5% and 44% were
      malnourished or at risk of malnutrition respectively. In depressed group, the
      prevalence of malnutrition was 14.5% (48 out of 330) and the prevalence of "at
      risk of malnutrition" was 45.8%, whereas the prevalence of malnutrition and at
      risk of malnutrition in non-depressed population were 10.6% and 43.3%
      respectively. From the aforementioned information we have concluded that there is
      a significant statistical difference between the prevalence of malnutrition in
      depressed and non-depressed individuals (P= 0.047). CONCLUSIONS: With respect to
      the high rate of vegetative symptoms in elderly depressed individuals,
      malnutrition would have a higher prevalence in the depressed people.

PMID- 23113075
TI  - Nitrous oxide levels in operating and recovery rooms of Iranian hospitals.
AB  - BACKGROUND: Nitrous oxide (N(2)O) is the oldest anesthetic in routine clinical
      use and its occupational exposure is under regulation by many countries. As
      studies are lacking to demonstrate the status of nitrous oxide levels in
      operating and recovery rooms of Iranian hospitals, we aimed to study its level in
      teaching hospitals of Tehran University of Medical Sciences. METHODS: During a 6
      month period, we have measured the shift-long time weighted average concentration
      of N(2)O in 43 operating and 12 recovery rooms of teaching hospitals of Tehran
      University of Medical Sciences. RESULTS: The results show that the level of
      nitrous oxide in all hospitals is higher than the limits set by different
      countries and anesthetists are at higher risk of exposure. In addition, it was
      shown that installation of air ventilation could reduce not only the overall
      exposure level, but also the level of exposure of anesthetists in comparison with
      other personnel. CONCLUSION: The high nitrous oxide level in Iranian hospitals
      necessitates improvement of waste gas evacuation systems and regular monitoring
      to bring the concentration of this gas into the safe level.

PMID- 23113076
TI  - Application of artificial neural network in predicting the survival rate of
      gastric cancer patients.
AB  - BACKGROUND: The aim of this study was to predict the survival rate of Iranian
      gastric cancer patients using the Cox proportional hazard and artificial neural
      network models as well as comparing the ability of these approaches in predicting
      the survival of these patients. METHODS: In this historical cohort study, the
      data gathered from 436 registered gastric cancer patients who have had surgery
      between 2002 and 2007 at the Taleghani Hospital (a referral center for
      gastrointestinal cancers), Tehran, Iran, to predict the survival time using Cox
      proportional hazard and artificial neural network techniques. RESULTS: The
      estimated one-year, two-year, three-year, four-year and five-year survival rates
      of the patients were 77.9%, 53.1%, 40.8%, 32.0%, and 17.4%, respectively. The Cox
      regression analysis revealed that the age at diagnosis, high-risk behaviors,
      extent of wall penetration, distant metastasis and tumor stage were significantly
      associated with the survival rate of the patients. The true prediction of neural
      network was 83.1%, and for Cox regression model, 75.0%. CONCLUSION: The present
      study shows that neural network model is a more powerful statistical tool in
      predicting the survival rate of the gastric cancer patients compared to Cox
      proportional hazard regression model. Therefore, this model recommended for the
      predicting the survival rate of these patients.

PMID- 23113077
TI  - Housewives' obesity determinant factors in iran; national survey - stepwise
      approach to surveillance.
AB  - BACKGROUND: Women suffer more from obesity than men in Iran do. In this study, we
      compared obesity risk and its contributors regarding the job categories as
      housewives (HWs) or employees to deeply explore the risk of obesity in housewives
      in Iran. METHODS: Based on WHO stepwise approach, in 2005, 33472 women aged 15 to
      65 years old (excluding all men) were examined for the major risk factors for non
      communicable diseases. Obesity was determined by Body Mass Index>30kgm(-2) in
      adults (>20 years) and by girl BMI percentiles according to WHO 2007 Growth
      Reference 5-19 years in adolescents. We modeled obesity by logistic regression
      and entered all the known/potential predictors, including job categories.
      RESULTS: The participation rate was more than 99%. The weighted prevalence of
      overweight and obesity in HWs were 34.5% and 24.5% respectively. Employed women
      were about 4% and 10% less overweight and obese than the HWs, respectively (P<
      0.01). HWs vs. employed women had the adjusted OR 1.39 (CI95%, 1.18-1.63) for
      obesity. Older women, with higher educational level and socioeconomic status,
      lower physical activities and those living in urban areas were at risk of
      obesity. In comparison to HWs, working as an Official Clerk (OR=0.66) associated
      with a decrease in odds of obesity significantly, while others did not.
      CONCLUSION: Being as HW is an independent significant factor for obesity in
      women. Preventive health care programs to reduce risk of obesity in women should
      be applied, considering their occupation for achieving more effectiveness.

PMID- 23113078
TI  - The Relationship between Obesity and Quality Of Life in School Children.
AB  - BACKGROUND: To determine relationships between healths related quality of life
      and body mass index in children aged 9-11 years old. METHODS: This cross
      sectional study was conducted on 240 children 9-11 year olds who were selected
      via multi stage cluster sampling design from primary schools in the Shahre Qods
      of the Tehran, Iran in 2007. Pediatric Quality of Life inventory was completed by
      child self report with measured height and weight used to determine body mass
      index percentile/weight classification. Obesity was defined as body mass index
      (BMI) >=95(th) percentile for age and gender and one way analyses of variance
      (ANOVA) was used for data analyses. RESULTS: Physical, social and school
      functioning was significantly lowered for obese when compared to normal weight
      children (P<.05). The impairment in QOL in the community-based sample of
      elementary school children was less marked than clinical sample of obese. Obese
      children maintain emotional health. CONCLUSION: These results highlight the
      importance in considering dimensions of quality of life at further understanding
      obesity in children.

PMID- 23113079
TI  - Beta-Carotene, Vitamin E, MDA, Glutathione Reductase and Arylesterase Activity
      Levels in Patients with Active Rheumatoid Arthritis.
AB  - BACKGROUND: Many studies have investigated the possible role of reactive oxygen
      species in the etiology and pathogenesis of Rheumatoid Arthritis (RA). The aim of
      this study was to investigate the activities of some antioxidants in RA patients.
      METHODS: In this case-control study, 59 RA patients and 60 healthy sex and age
      matched controls were selected. Vitamin E and Beta-carotene were determined using
      HPLC. Erythrocytes glutathione reductase (GR) activity was measured
      spectrophotometrically, and malondialdehyde (MDA) was determined by colorimetric
      method. Arylesterase activity (AEA) was measured by Phenylacetate. The clinical
      data were determined by a rheumatologist, medical history and filling the
      questionnaire by interview. Statistical analyses were carried out using the SPSS
      software. RESULTS: In patients with RA, serum MDA level was significantly higher
      and plasma concentration of vitamin E, Beta-carotene and GR activity, were
      significantly lower than healthy control (P< 0.001). AEA activity differences
      between two groups were non-significant. CONCLUSIONS: Oxidative stress may play
      an important role in the inflammation and pathogenesis of RA.

PMID- 23113080
TI  - Trends in Prevalent Injuries among Iranian Pilgrims in Hajj.
AB  - BACKGROUND: Annually millions of Muslims depart to Saudi Arabia for performing a
      religious pilgrimage called "Hajj". In this ceremony, pilgrims face numerous
      health hazards and injuries such as pressing in overcrowding, sliding, burning,
      falling down, traffic accidents etc. The main purpose of this study was to
      determine the prevalence of injuries in Hajj period across 2004 to 2008. METHODS:
      This study was conducted on 253808 Iranian pilgrims on five consecutive years of
      Hajj ceremonies, from 2004 to 2008. We used a report sheet with 13 types of
      injuries and 13 mechanisms of these injuries. SPSS V13.5 soft ware was used for
      analyzing the data. ANOVA and independent sample t - test was conducted, and
      relationships were considered significant at P< 0.05. RESULTS: The most common
      injuries was "tissue contusions and ruptures "(about 76/10000), and "tendon
      lesions" (about 62/10000). In addition, the most common mechanism of injuries was
      "ankle sprain" (69/10000) during the five consecutive years. The prevalence of
      all fractures was about 49/10000 and the proportion of burning with hot water or
      fire was about 40/10000. Changes of all causes of the injuries were significant
      in this study (P< 0.05). CONCLUSIONS: We have suggested some directions for
      preventing of injuries and related Injuries in Hajj, in this study.

PMID- 23113082
TI  - Iodine deficiency disorder control programme impact in pregnant women and status
      of universal salt iodization.
AB  - BACKGROUND: Several studies pertaining to current status of Iodine Deficiency
      Disorder Control Programme in India have revealed goiter prevalence in the range
      of 1.5-44.5%, mean urinary iodine excretion level ranging from 92.5-160 mcg/L and
      iodized salt coverage ranging from 37-62.3%. Most of these studies were based on
      school children. However, very few studies have focused on pregnant women. This
      population is very sensitive to marginalized iodine deficiency throughout their
      gestational period. METHODS: This 40 cluster cross sectional study was done in
      Raipur district. Iodine content of salt was estimated by using "Rapid Salt
      Testing Kits" along with observing salt storage practices, at household and in
      shops. Pregnant women were interviewed by using semi structured comprehensive
      questionnaire, which was based on knowledge attitude, and practices about salt
      use pattern and awareness about IDDCP, UIE level were also estimated. RESULTS:
      Prevalence of goiter was 0.17%. Many (41.12%) pregnant women had <15ppm iodine
      content in the salt sample and 51.58% of women had subnormal iodine uptake. Wrong
      salt storage practice was observed in 36.3% of households. CONCLUSIONS: There
      were lacunae in Iodine deficiency control program in Chhattisgarh. Implementation
      and monitoring of program was weak. Thus for monitoring purpose IDD Cell & IDD
      Laboratory should be established at district level. This will lead to periodic
      assessment of Iodine Deficiency Disorders, by monitoring of Iodine intake and all
      other preventive, promotive as well as curative measures in the state.

PMID- 23113081
TI  - Emergence of q Fever.
AB  - Q fever is a worldwide zoonosis with many acute and chronic manifestations caused
      by the pathogen Coxiella burnetii. Farm animals and pets are the main reservoirs
      of infection, and transmission to human beings is mainly accomplished through
      inhalation of contaminated aerosols. Persons at greatest risk are those in
      contact with farm animals and include farmers, abattoir workers, and
      veterinarians. The organs most commonly affected during Q fever are the heart,
      the arteries, the bones and the liver. The most common clinical presentation is
      an influenza-like illness with varying degrees of pneumonia and hepatitis.
      Although acute disease is usually self-limiting, people do occasionally die from
      this condition. Endocarditis is the most serious and most frequent clinical
      presentation of chronic Q fever. Vascular infection is the second most frequent
      presentation of Q fever. The diagnosis of Q fever is based on a significant
      increase in serum antibody titers. The treatment is effective and well tolerated,
      but must be adapted to the acute or chronic pattern with the tetracyclines to be
      considered the mainstay of antibiotic therapy. For the treatment of Q fever
      during pregnancy the use of long-term cotrimoxazole therapy is proposed.

PMID- 23113083
TI  - Prevalence of obesity in adolescents with history of pregnancy and associated
      factors in Korea.
AB  - BACKGROUND: The pregnancy was a risk factor for excessive weight gain for women.
      However, there is no information about the prevalence of obesity and its
      relationship with a history of pregnancy in girls. Therefore, the purpose of this
      study was to investigate differences in the prevalence of obesity in adolescent
      females with a history of pregnancy and factors associated with it, in Korea.
      METHODS: In 2009, 69 of 34,247 female students revealed that they had experienced
      pregnancy in response to the 5(th) Korea Youth Risk Behavior Web-based Survey
      (KYRBWS-V) project by the Korea Centers for Disease Control and Prevention
      (KCDCP). The body mass index (BMI) and experienced pregnancy categories of the
      KYRBWS-V were assessed, and, for data analysis, the independent t-test, chi
      square test, and multivariate logistic regression were used. RESULTS: The risk of
      pregnancy was increased by approximately 47% per unit increase in age, and 331%
      per unit increase in depression, respectively. Conversely, the risk decreased by
      19% per unit increase in BMI and 33% per unit increase (ranged from 1: very rich
      to 5: very poor) in the family economic state. CONCLUSION: Obesity in adolescent
      females is minimally affected by a history of pregnancy, if at all, despite the
      fact that pregnancy was a risk factor for excessive weight gain in women.
      However, adolescent females with a history of pregnancy have higher levels of
      depression than do normal peers in Korea.

PMID- 23113084
TI  - The Use of Obesity Indicators for the Prediction of Hypertension Risk among Youth
      in the United Arab Emirates.
AB  - BACKGROUND: Obesity is a significant risk factor for metabolic disorders
      including increase in blood pressure. Body mass index (BMI), waist circumference
      (WC) and Waist/Hip ratio (WHR) are simple and effective indicators of obesity.
      The objectives of this study were to examine the relationships between obesity
      anthropometric indicators and hypertension and to identify the best
      anthropometric indicator/s that can predict hypertension risk among youth in the
      UAE. METHODS: A 110 first year students in a Medical University in Ajman, UAE,
      during the year 2009-2010 were included in a cross-sectional study. The height,
      weight, WC, hip circumference and blood pressure were measured and the BMI and
      WHR were calculated for each student and used in the analyses. RESULTS: The mean
      values for BMI, WC, hip circumference and WHR, were significantly higher in the
      Pre/Hypertensive group compared to normal blood pressure group. The risk of Pre/
      hypertension was significantly increased by 4.3 times for participants who had
      general obesity (BMI>= 30) or abdominal obesity (identified from high WC). Highly
      significant correlations were noticed between systolic and diastolic blood
      pressure and all anthropometric indicators except that for Hip circumference and
      systolic blood pressure. Step-wise linear regression model showed that when all
      obesity indicators were studied together, the waist circumference was the only
      indicator which showed significant relationship with both systolic and diastolic
      blood pressure. CONCLUSION: Waist circumference is the best anthropometric
      indicator that can predict hypertension risk among youth in the UAE.

PMID- 23113085
TI  - Respiratory Hospital Admissions before and after Closure of a Major Industry in
      the Lower Hunter Region, Australia.
AB  - BACKGROUND: Many epidemiological studies reported significant associations
      between air pollution and respiratory hospital admissions. Proximity of
      industries to the residential areas may have considerable impacts on air quality
      and subsequently public health. This paper describes the indirect impacts of
      closing a large steel industry, Broken Hill Proprietary (BHP), in the Lower
      Hunter region, Australia. METHODS: The number of hospital admissions for a group
      of respiratory diseases including all respiratory disease, Chronic Obstructive
      Pulmonary Disease (COPD) and asthma were incorporated in this study. The study
      location comprised the entire Lower Hunter, Newcastle, as the closest location,
      and Port Stephens, as the most distant area to the industry. Two series of data
      set for 3.5 years before and after industry closure allowed a comparison of daily
      hospital admissions. Mixed Model was employed to calculate significant changes in
      the time series by month. RESULTS: While the rest of the disease categories
      decreased, COPD 65+ increased after BHP closure. All-age asthma in Newcastle
      showed the highest decrease whereas the least difference was observed for
      respiratory disease in Port Stephens. The decrease of admission rates was
      generally more significant in Newcastle, where the industry was operating, than
      in the other areas. CONCLUSION: Inconsistent results challenged the publically
      viewed significant role of BHP closure on public health. The study expected
      consistent decreases of respiratory admissions after industry closure; however,
      the district results suggested some impacts on community health. Incompatible
      findings could be attributable to other factors that dominated the possible
      impacts of BHP closure.

PMID- 23113086
TI  - The prevalence of diabetic peripheral neuropathy and related factors.
AB  - BACKGROUND: Diabetic peripheral neuropathy (DPN) accounts for 80% of diabetic
      foot ulceration; therefore neurologic examination plays a critical role in
      screening at risk patients. Our objective was assessment the prevalence of DPN
      and related factors based on clinical findings. METHODS: This cross-sectional
      study was conducted on 124 diabetics who were randomly recruited from Diabetes
      Clinic of Dr. Shariati University Hospital (Tehran/Iran) in 2004. After gathering
      demographic data and blood sampling for fasting blood sugar (FBS), the
      questionnaires United Kingdom (UK), Michigan, Diabetic Neuropathy Score (DNS),
      and 10-g monofilament testing were administered. Analysis tests were chi-square,
      pearson correlation and logistic regression. RESULTS: The patient's age ranged 17
      75 years; with 44% male. Ninety one percent suffered from type two diabetes and
      the mean duration of diabetes was 10 years. The mean FBS level was 181.5 mg/dl.
      While the prevalence of DPN based on Michigan, DNS, and monofilament testing was
      about 32-38%, some 54% were diagnosed by UK test. Tingling in the lower extremity
      was the most frequent complaint (42%). The strongest linear correlation was
      reported between Michigan and DNS (r= 0.7), and then between monofilament test
      and DNS (r= 0.6). The age > 50 years, length of diabetes > 10 years, and FBS >200
      mg/dl were the main risk factors for DPN based on DNS. CONCLUSION: It seems that
      the combination of Michigan and monofilament test can provide an accurate
      screening tool for detecting DPN. In addition, tight glucose control, regular
      assessment of the lower extremity, and to educate diabetics is urged in elderly
      diabetics, longer duration of diabetes, and those with high FBS.

PMID- 23113087
TI  - Hypertension in Iranian urban population, epidemiology, awareness, treatment and
      control.
AB  - BACKGROUND: To assess the epidemiological characteristics of hypertensive
      patients in urban population of Yazd, A central city in Iran. METHODS: This cross
      sectional study was conducted from 2005-2006 and carried out on population aging
      20-74 years. It is a part of the phase I of Yazd healthy heart program that it is
      a community interventional study for prevention of cardiovascular disease. Data
      obtained from questionnaires were analyzed by SPSS version 13. P value less than
      0.05 were considered significant level. RESULTS: This study comprised of 2000
      participants that 847 (42.5%) were diagnosed as being hypertensive. After age
      adjustment, prevalence of hypertension was 25.6% (23.3% for women and 27.5% for
      men (P< 0.001). Age, Total cholesterol, LDL-cholesterol, triglyceride, fasting
      blood glucose, impaired glucose tolerance test, body mass index and waist were
      significantly higher in the hypertensive groups. 53.7% of hypertensive cases were
      aware of own condition, 45% were treated, and 33.9% of treated were controlled
      (30.7% and 35.4% in men and women respectively). In other word, 24% of all
      hypertensives (aware or unaware about own blood pressure condition) were treated
      and only 8% of them were controlled. Men significantly had less awareness (P<
      0.001), lower tendency to take medication (P< 0.001), and less were controlled
      (P= 0.046). CONCLUSION: We understand high prevalence, low awareness, treatment,
      and control of hypertension and higher prevalence of other traditional metabolic
      risk factors in these cases. It seems that urgent preventional studies should be
      conducted in this population.

PMID- 23113088
TI  - The role of health environment and location in the emergence of urban criminal
      behaviours in tehran.
AB  - BACKGROUND: Although, the roots of criminal behaviours clearly lie in social,
      economic, and cultural factors, the increase criminal offences in urban settings
      has raised the issue of prevention through urban environmental health, planning
      and design. METHODS: The approach of the study was based on the scientific
      research methodology and indicators were compiled from observations and
      comparative analyses of those urban spaces that are most often the sites of
      crime. RESULTS: Pearson's correlation coefficient showed that 37% of sampled
      males and 51% of females emphasized on effectiveness of environmental factors.
      The urban space observations show that the environmental and physical factors
      affect on security and sensation of community safety among the citizens.
      CONCLUSION: Crime is committed in a particular place; place-related factors play
      a role in creating the potential for crimes to be committed. The results show the
      close bond between crimes and environmental problems.Recognition of the influence
      of location-specific characteristics and the correct environmental response may
      make it possible to prevent or at least reduce criminal acts in urban places.

PMID- 23113089
TI  - An Explanatory Model of Depression among Female Patients in Fars, Kurds, Turks
      Ethnic Groups of Iran.
AB  - BACKGROUND: Depressive disorder is globally estimated to be as many as one in
      five visits to primary health care. Approximately more than 50% of depressed
      women in primary care are not diagnosed. As a part of a major investigation into
      perceptions of women's depression, this study explored how female patients and
      their relatives conceptualize patients' conditions in three ethnic groups in Iran
      (Fars, Kurds and Turks). METHODS: Qualitative methods were used for data
      collection. Depressed women and their relatives were purposively selected from
      the public psychiatric clinics affiliated to university of medical sciences in
      the three study cities. Twenty-five depressed women and 14 relatives were
      interviewed in three ethnic groups. RESULTS: One theme "illness meaning",
      including three categories: perceived symptoms, label of the illness, and effects
      of the illness was found through the content analysis. The participants perceived
      symptoms of illness as somatic and psychological depending on the participant's
      assumed reason for the onset of the illness. There were most similarities in term
      used for of the illness in the three ethnic groups. Most of the study
      participants described the illness in terms of nerve problems/illness, and
      depression "afsordehgi". The most important effects that depressed women had
      experienced because of their illness were marital conflict or a guilt feeling
      originating from their inability to support family. CONCLUSION: These findings
      suggest the need to recognize and choose appropriate diagnostic approach for
      depressed women in the context of Iran.

PMID- 23113090
TI  - Assessing a group of physicians' ethical sensitivity in Turkey.
AB  - BACKGROUND: The objective was to measure the sensitivity of a group of physicians
      regarding the ethics-related situations, which they faced during patient care and
      treatment. METHODS: All of 306 physicians who joined the Turkish Army for
      compulsory military service in December 2008 were included in the study. A "Moral
      Sensitivity Questionnaire", formed by Kim Lutzen, was applied to all of them.
      RESULTS: From total, 95% of physicians performed their job willingly, 88% of
      physicians attended ethic lessons (n=265), 72.4% (n=218) followed ethic
      publications, 67.4% (n=203) stated that there was an ethic committee at their
      institutions, and 5% worked as a member of the ethic committee. There were
      statistically significant differences between autonomy, benevolence meaning,
      conflict, and total scores according to workplace of physicians, employment
      period, and being specialists. Points of autonomy were found lower in physicians
      working at private hospital and health center than those at public hospital.
      CONCLUSION: Ethical sensitivity of physicians changed due to work place. We
      conclude that organizational arrangements are of beneficial effects to increase
      ethical sensitivity.

PMID- 23113091
TI  - Prevalence and characterization of listeria species in domestic and industrial
      cheeses of isfahan region.
AB  - BACKGROUND: Listeria monocytogenes is of major concern to the food industry in
      general and the dairy industry in particular. Little is known about incidence of
      this pathogenic bacterium in dairy products in Iran. METHODS: A survey was made
      from 23 September 2006 to 22 June 2007 for Listeria species in ninety samples of
      traditional and industrial cheeses, in milk and surface where the cheeses were
      manufactured from unpasteurized raw milk in the province of Isfahan (Iran).
      RESULTS: Listeria murrayi, L. grayi and L. ivanovii, were detected in nine
      traditional cheeses and one raw milk sample. None of the different Listeria
      species were isolated from the industrial cheeses and their environment.
      CONCLUSION: There are almost good hygienic conditions in domestic cheese
      manufacturing farmhouses in Isfahan area, but we should try to improve hygienic
      levels until we have none of the Listeria spp. in our samples.

PMID- 23113092
TI  - Predictive Power of Incidents Reporting Rate and Its Dimensions by Job Stress
      among Workers' Isfahan Steel Company.
AB  - BACKGROUND: There is long-term interest in the effects of stress on health, due
      to the strain that it places on individuals which can lead to an increased risk
      of disease. The present study examined degree of perceived job stress related to
      incidents reporting rate and its dimensions among workers' Isfahan Steel Company.
      METHODS: A self-administered anonymous was distributed to 189 workers. The survey
      included demographic factors, incidents reporting rate and its components
      (physical symptoms, psychological symptoms and accidents) and the Job Stress
      Questionnaire. The data were analyzed by multivariate (MANOVA) and correlation
      techniques. RESULTS: 1) there was internal significant correlation between
      perceived job stress with incident reporting rate as well as with its two
      components namely physical symptoms and psychological symptoms; 2) there was not
      a significant relationship between perceived job stress and accident; 2) In
      multivariate analysis, perceived job stress respectively about 12%, 18% and 19%
      of the variance of variables of incidents reporting rate, physical and
      psychological symptoms significantly predicted (P< 0.05). CONCLUSION: Perceived
      job stress influences to physical and psychological symptoms. Therefore,
      decreasing job stress can be important to prevent the development of stress
      related diseases and to promote workers health.

PMID- 23113093
TI  - Prevalence of HPV Infection and High Risk HPV Genotypes (16, 18), among
      Monogamous and Polygamous Women, In Zabol, Iran.
AB  - BACKGROUND: This study was performed to compare the prevalence of HPV infection
      and high risk HPV genotypes [16, 18] between monogamous and polygamous women, in
      Zabol, Iran. METHODS: This cross sectional study was conducted in Zabol in 2006 -
      2007. Two hundred sixty five married women attending the Gynecology Clinic for
      Cervical Disease Screening entered to this study. One hundred sixty two cases had
      monogamous, and 103 had polygamous husbands. HPV PCR samples were obtained from
      scrape of papsmear specimens. The biotinylated primers MY09/MY11, GP5+/GP6+, were
      utilized to enable amplification and detection of positive PCR products.
      Confirmation of HPV-16 and -18 were done by type-specific PCR primers HPV-16/F,
      HPV-16/R and HPV-18/F, HPV-18/R. RESULTS: Prevalence of HPV infection in
      monogamous and polygamous groups was 29% and 37.9%, respectively. The most HPV
      infection was found in 15-25 years group. The most prevalence of infection in
      monogamous group was HPV-18 and HPV-non16, 18 in 15-25 years, and HPV-16 in 26-35
      years group. In polygamous group the most prevalent type was HPV-16, 18 in 15-25
      years group. The most prevalent HPV-16 was seen in sever inflammation and
      dysplasia cytology in both groups. CONCLUSION: Prevalence of HPV infection in
      Zabol is high, and in women with polygamous husbands group is slightly more than
      monogamous. Screening for this infection must be recommended in this region of
      Iran.

PMID- 23113094
TI  - Effect of periodontal disease on preeclampsia.
AB  - BACKGROUND: A lot of studies have shown periodontal diseases as a risk factor for
      adverse pregnancy outcomes. The association between periodontitis and
      preeclampsia has been studied recently with controversy. Considering the
      importance of preventing preeclampsia as a dangerous and life-threatening disease
      in pregnant women, the present study was carried out. METHODS: Two hundred and
      ten pregnant women participated in this case-control study (105 controls & 105
      cases) during years 2007 and 2008. Preeclamptic cases were defined as blood
      pressure >=140/90mmHg and proteinuria +1. Control group were pregnant women with
      normal blood pressure without proteinuria. Both groups were examined during 48
      hours after child delivery. Plaque Index (PLI), Pocket Depth (PD), Clinical
      Attachment Level (CAL), Bleeding On Probing (BOP), Gingival Recession (GR) were
      measured on all teeth except for third molars and recorded as periodontal
      examination. Data was analyzed using t-test, chi-square, and Mann-Whitney U
      statistical tests. RESULTS: There was no significant difference between the two
      study groups for PD. CAL, GR, BOP significantly increased in the case group (P<
      0.02). This study showed that preeclamptic cases were more likely to develop
      periodontal disease (P< 0.0001). Eighty three percent of the control group and
      95% of the case group had periodontal disease (P< 0.005) which had shown that
      preeclamptic cases were 4.1 times more likely to have periodontal disease (OR=
      4.1). CONCLUSION: Preeclamptic cases significantly had higher attachment loss and
      gingival recession than the control group.

PMID- 23113095
TI  - Determinants of health related quality of life on people living in bandar abbas,
      iran.
AB  - BACKGROUND: The relationship between socio demographic status and Health Related
      Quality of Life (HRQOL) has not been well documented in most population of Asian
      countries including Iran. This study aimed to investigate the determinants of
      HRQOL in general population living in Bandar Abbas. METHODS: This cross sectional
      study was conducted among general population living in Bandar Abass, Iran from
      Jun to Jul, 2007. Using a multistage sampling method, a random sample of
      individuals aged 15 years and over were interviewed through SF-36 questionnaire
      .Multiple logistic regression analysis were used to predict determinant factors
      on health related quality of life. RESULTS: Overall, 1675 Iranian adults were
      interviewed. The majority of the participants were female (50.4%), married
      (70.9%) and employed (36.8%). The range of education years of most participants
      (56.7%) were from 6 to 12 years. Female participated in this study had
      significantly poorer HRQOL than male in all aspects of SF-36 except for Role
      Emotional (P< 0.001). Furthermore there were significant differences between
      different age groups in all individually scales and two summaries (P< 0.001).
      After adjusting for the impacts of other socio demographic factors, variable such
      as older age, female gender and lower educational level could independently
      decrease both mental and physical aspect of HRQOL (P< 0.01). CONCLUSION: Female,
      older and less educated people are at higher risk of poorer health quality of
      life in both mental and physical aspects and should be considered as high risk
      groups in priority health programs.

PMID- 23113096
TI  - The role of family physician in case finding, referral, and insurance coverage in
      the rural areas.
AB  - BACKGROUND: WHO suggest that family physician is the core in the world efforts
      for quality improvement, cost effectiveness, and equity in the health care
      systems. This study evaluates the impact of the program on accessibility of the
      services, case finding, patient referral, feedback process and insurance coverage
      in the rural health units. METHODS: This study was quasi experimental. It
      compared the function of four health centers and eight health houses in the last
      three months of year 2004 with 2008. Data extracted from the available documents
      in the health units. Descriptive and analytical analysis was performed by using
      SPSS software. RESULTS: The presence of physicians in health centers were 75 and
      100 percent for 2004 and 2008 respectively, this rate for midwives were 50 and
      100 percent for the same years respectively. The total referral cases to the
      hospitals were 2676, the feedback rate was recorded in 36% of the cases. In this
      case the follow up rate by physicians was 0% in 2004 and 3.17% in 2008. Insurance
      coverage rate was 27% and 97% for 2004 and 2008 respectively within a meaningful
      P value range at 95% CI. CONCLUSION: The findings of this study show that the
      family physician program has the positive impact on function of health units in
      terms of availability of physicians and midwives and also insurance coverage at
      health centers in rural area, No impact on patient follow up and case referral
      rate was detected.

PMID- 23113097
TI  - Stepwise excavation: a conservative community-based dental treatment of deep
      caries to inhibit pulpal exposure.

PMID- 23113098
TI  - More realistic estimate for maternal mortality ratio in iran.

PMID- 23113099
TI  - Aflatoxins in iran: nature, hazards and carcinogenicity.
AB  - Many studies have shown that mycotoxin contamination of agricultural products is
      a challenge for individual's health especially in developing countries. Improper
      production and storage of foods, prepare conditions for aflatoxin production in
      crops, especially rice, wheat, pistachio, walnut, almond, etc which are the main
      sources of foods for people. Feeding livestock by contaminated bread is another
      way of human exposure to mycotoxins, especially aflatoxin and because of
      expensive methods for detecting and analyzing aflatoxin in laboratory; it is not
      measured in foods. This manuscript is a review of some Iranian and nonIranian
      reports about aflatoxin, its exposure ways, its adverse effect on human health
      and nutrition, as well as methods for reducing its exposure. Based on studies on
      foods, aflatoxin exposure is high in Iran. Since livestock feeding by
      contaminated bread is one of the potential ways for milk contamination, we should
      control and reduce aflatoxin contamination by improving production process,
      storage condition and livestock feeding as soon as possible. Pistachio is one of
      the most important exporting products of Iran and to maintain Iran's position in
      exporting of this product, specific regulations on lowering its contamination
      with aflatoxin should be considered seriously. Finally, effective controlling of
      all food and feedstuffs which are vulnerable to aflatoxin contamination is
      necessary to prevent its effects.

PMID- 23113100
TI  - Challenges in achieving food security in India.
AB  - First Millennium Development Goal states the target of "Halving hunger by 2015".
      Sadly, the recent statistics for India present a very gloomy picture. India
      currently has the largest number of undernourished people in the world and this
      is in spite of the fact that it has made substantial progress in health
      determinants over the past decades and ranks second worldwide in farm output. The
      causes of existing food insecurity can be better viewed under three concepts
      namely the: 'traditional concept' which includes factors such as unavailability
      of food and poor purchasing capacity; 'socio-demographic concept' which includes
      illiteracy, unemployment, overcrowding, poor environmental conditions and gender
      bias; 'politico-developmental concept' comprising of factors such as lack of
      intersectoral coordination and political will, poorly monitored nutritional
      programmes and inadequate public food distribution system. If the Millennium
      Development Goal is to be achieved by 2015, efforts to improve food and nutrition
      security have to increase considerably. Priority has to be assigned to
      agriculture and rural development along with promoting women empowerment,
      ensuring sustainable employment and improving environmental conditions (water,
      sanitation and hygiene). As the problem is multi-factorial, so the solution needs
      to be multi-sectoral.

PMID- 23113101
TI  - Association between Times Spent on the Internet and Weight Status in Korean
      Adolescents.
AB  - BACKGROUND: This study investigates whether the amount of time that Korean
      adolescents spend on the Internet per day is related to their weight status.
      METHODS: For this purpose, we analyzed data from the 2009 Korea Youth Risk
      Behavior Web-based Survey-V (KYRBWSV), in which 72,399 students from the 7(th) to
      the 12(th) grade participated. We assessed the relationship between the amount of
      time spent on the Internet per day and body mass index (BMI) by using
      multivariate logistic regression analysis. RESULTS: For boys, the odds ratio (OR;
      confidence interval (CI): 95%) between becoming overweight and the amount of time
      spent on the Internet per day was 1.225 (1.042-1.441; P=0.014) for >4 hour. The
      ORs (CI: 95%) between becoming obese and time spent on the Internet per day were
      1.238 (1.096-1.399; P=0.001) for >2-<=3 hours, 1.208 (1.021-1.428; P=0.027) for
      >3-<=4 hours, and 1.303 (1.109-1.532; P=0.001) for >4 hours. For girls, the ORs
      (CI: 95%) between becoming overweight and time spent on the Internet per day were
      1.265 (1.089-1.469; P=0.002) for >2-<=3 hours and 1.338 (1.080- 1.659; P=0.008)
      for >3-<=4 hours. The ORs (CI: 95%) between becoming obese and amount of time
      spent on the Internet per day were 1.239 (1.014-1.513; P=0.036) for >2-<=3 hours
      and 1.541 (1.182-2.010; P=0.001) for >3-<=4 hours. CONCLUSION: Korean adolescents
      who spend more time on the Internet are predisposed to weight-related problems,
      regardless of age, time spent in physical exercise, mental stress, sleep
      duration, etc.

PMID- 23113102
TI  - Predictors of Handgrip Strength among the Free Living Elderly in Rural Pahang,
      Malaysia.
AB  - BACKGROUND: Reduced handgrip strength is an aging process that significantly
      influences the living activities of elderly. It is linked to premature mortality,
      disability and other health complications among elderly. Therefore, we aim to
      determine the associated predictors with handgrip strength among the free living
      elderly in Malaysia. METHODS: This was a cross sectional study conducted in a
      rural state in Malaysia. A total of 434 elderly individuals performed handgrip
      assessment. Socio-demographic characteristics, medical conditions, occupational
      history, functional ability (ADL) and depression (GDS) were enquired.
      Anthropometric measurements (weight and height) were also obtained. RESULTS:
      Majority of the respondents were Malays with mean age of 67.9 +/- 6.3 years.
      Maximum handgrip strength of males and females were 28.8+/-9.2 kg and 18.9+/-6.9
      kg respectively (P<0.05). The aborigines had significantly lower handgrip
      strength (P<0.05) compared to Malays, Chinese and Indians. Handgrip strength was
      positively correlated (P<0.05) with weight, height and ADL, while negatively
      associated (P<0.05) with GDS for both gender. In the multivariate linear
      regression analysis; weight, height and race significantly predicted handgrip
      strength among both male and female elderly after adjustment for all potential
      confounders. However, GDS and ADL were only found to significantly predict
      handgrip strength among the male elderly; while age was only significant among
      the females. CONCLUSION: Our sample population has significantly lower handgrip
      strength than the Western counterpart. Weight, height and race significantly
      predict handgrip strength among both male and female elderly. GDS, ADL are only
      found to be significant in males while age was only significant among the
      females.

PMID- 23113103
TI  - An exploration of prevalence and associated factors of nonalcoholic Fatty liver
      disease in the taiwanese police service.
AB  - BACKGROUND: The purpose of this study was to explore any gender-related
      differences in prevalence of and condition-associated factors related to non
      alcoholic fatty liver disease (NAFLD) amongst police population in Taipei,
      Taiwan. METHODS: We studied a total of 1016 healthy adults with police work (972
      males and 44 females) voluntarily admitted to physical check-up between January
      2006 and December 2006. Blood samples and ultrasound-proved fatty liver
      sonography results were collected. RESULTS: The prevalence of NAFLD for this sub
      population was found to be 52.2%, the prevalence revealing a statistically
      significant decrease with increasing population age (P<0.001). Males exhibited a
      greater prevalence of NAFLD than did females (53.6% vs 20.5%, P<0.0001). Using
      multiple logistic regression analysis, in addition to male gender, an older age,
      higher BMI, higher ALT, presence of hyperuricemia, hypercholesterolemia, and
      hypertriglyceridemia were the significant factors associated with NAFLD. Gender
      related differences as regards associated factors were also revealed. For males,
      hyperuricemia (OR=1.35, 95%CI: 1.07-1.86), higher ALT (OR=2.31, 95%CI: 1.50
      3.56), hypercholesterolemia (OR=1.33, 95%CI: 1.01-1.82), and hypertriglyceridemia
      (OR=1.55, 95%CI: 1.01-2.37) were significantly related to NAFLD but these were
      not so for females. CONCLUSION: several gender-related differences were noted
      pertaining to the prevalence of and relationship between hyperuricemia, higher
      ALT, hypercholesterolemia, and hypertriglyceridemia and NAFLD in the present
      study.

PMID- 23113104
TI  - Eruption time of permanent teeth in pakistani children.
AB  - BACKGROUND: To determine the mean eruption time of permanent teeth of Pakistani
      children and to evaluate the effects of gender, type of schools, height, weight
      and body mass index on it. METHODS: This cross sectional study was conducted from
      September 2007 to April 2008. 4370 children of 'just erupted' teeth were obtained
      from 102 randomly selected schools from 18 towns of Karachi, using systematic
      random sampling procedure. The dental examination was carried out for the
      selected child. Height, weight and date of birth were also obtained. Two
      sample't' test and paired 't' test were employed to compare the mean time of
      eruption between gender and type of schools (private/ public), and upper and
      lower jaws. Pearson and partial correlations were used to determine the
      significant relationship between eruption time with height, weight and BMI.
      RESULTS: The right first molars of upper and lower jaws showed the minimum
      eruption time. Second molars were the last tooth to emerge. Only 3 teeth showed
      significant difference of eruption time between the genders. None of
      contralateral teeth showed any statistical significant difference. All the
      mandible teeth, except the premolars, erupted earlier than maxillary teeth.
      Private schools children showed early eruption than the public schools children.
      The Pearson and partial correlation were significant positively correlated with
      height. Eruption time of all the teeth, except one, showed positive correlation
      with weight. CONCLUSION: The eruption time of Pakistani children are different in
      many aspects with to other nationalities.

PMID- 23113105
TI  - Expected survival using models of life table compared with survival of
      gastrointestinal tract cancer patients in north of iran.
AB  - BACKGROUND: Northern regions of Iran have been encountered to dominate
      malignancies of gastrointestinal (GI) tract. We came to examine the total excess
      mortality due to the GI cancer in Mazandaran province. METHODS: Socio-demographic
      and clinical data of 484 patients with GI cancer collected during the years 1990
      1991 were available from Babol Cancer Registry. Patients were followed up for 15
      years by the year 2006. Using the West Coale-Demeny life table model, a number of
      five life tables for men and four for women, corresponding to each birth cohort,
      were constructed. Observed survival was obtained using the Kaplan-Meier method
      and compared with the Expected survival calculated using the direct adjusted
      method represented by STEIN et al. RESULTS: The sample of subjects encompassed
      66.3% men and 33.7% women with mean age 58.26 +/- 10.90, and endoscopy was the
      general method for cancer detection. Esophagus accounted for 74.2%, and stomach
      and colorectal accounted for 22.7% and 3.1% of GI cancers, respectively. Survival
      rate in 15 years following diagnosis was nearly 6%. Comparing patient and
      expected survival curves showed a significantly reduced survival for patients of
      each GI cancer over the whole period and especially during the first two years
      after diagnosis. CONCLUSION: Patients experienced reduced survival associated
      with the development of GI cancers. Considering individuals in a population come
      from different cohorts, adjustment by constructing distinct life tables for
      different birth cohorts is recommended. The West model is recommended as a first
      choice to represent mortality in countries whose registration systems are exposed
      to various errors.

PMID- 23113106
TI  - Serum zinc levels in children and adolescents with type-1 diabetes mellitus.
AB  - BACKGROUND: There have been very few studies, with contradictory results, on the
      zinc status of children and adolescents with type-1 diabetes mellitus. The
      objective of this cross-sectional study was to determine zinc status based on the
      serum zinc concentration in type-1 diabetic children and adolescents and compare
      it with that of healthy controls. METHODS: Thirty children and adolescents with
      type-1 diabetes mellitus, aged 6 to 18 years, and 30 age- and sex-matched healthy
      controls participated in the study. Serum zinc, fasting blood sugar, hemoglobin
      A(1c) and serum albumin were measured by flame atomic absorption
      spectrophotometry, enzymatic colorimetry, ion-exchange chromatography and
      colorimetry using bromocresol green methods, respectively. RESULTS: No
      statistically significant difference was found in the mean serum zinc
      concentration between diabetic patients and healthy controls (111.0 +/- 3.1 and
      107.1 +/- 3.8 mg/dl respectively, P= 0.4). No correlations were found between the
      serum zinc levels and fasting blood sugar, hemoglobin A(1c), or the duration of
      the disease in the patients. CONCLUSION: The zinc levels of diabetic children and
      adolescents are not noticeably different compared to those of healthy controls
      and are independent of glycemic control and the duration of the disease.

PMID- 23113107
TI  - Physical activity, nutrition, and dyslipidemia in middle-aged women.
AB  - BACKGROUND: Cardiovascular disease is a major cause of death throughout the
      world. The aim of this study was to assess the prevalence of overweight/obesity,
      central obesity, hypertension and dyslipidemia, as well as dietary factors
      contributing to the development of dyslipidemia among middle-aged women. METHODS:
      The research design of the present study was a population-based cross-sectional
      study; anthropometric measures and blood chemistry were obtained. Physical
      activity was measured using the original International Physical Activity
      Questionnaires Long Form while food frequency questionnaire (FFQ) was used in
      assessing individual's habitual intake. Overall, 809 women, 30-50 years of age
      from fourteen active urban Primary Healthcare Centers (PHC) in Babol City,
      northern Iran, were obtained from 1,905 households across operational areas of 14
      PHC using systematic random sampling method. RESULTS: The prevalence rates of
      women classified as overweight/obese, with central obesity, hypertension and
      dyslipidemia were 82.8%, 75.5%, 14.6% and 63.4%, respectively. Total physical
      activity did not correlate with cholesterol ratio. Soybean protein was inversely
      associated with cholesterol ratio (rho=-0.18, P<= 0.001). The adjusted OR for
      dyslipidemia in women with moderate protein intake was significantly higher than
      in women with high and low intake (OR=2.31; 95% CI= 1.61, 3.30). No significant
      associations were found between dyslipidemia and carbohydrate, fat intake or
      physical activity. CONCLUSION: This study showed very high prevalence of
      cardiovascular disease risk factors among Iranian middle-aged women. A more
      detailed study is suggested to develop definitively recommendations for the
      primary and secondary prevention of cardiovascular disease for the Iranian
      population.

PMID- 23113108
TI  - The prevalence and clinical study of galactosemia disease in a pilot screening
      program of neonates, southern iran.
AB  - BACKGROUND: The aim of the study was to research concerning the epidemiology of
      newborns' galactosemia during 2007-2008 to find out whether screening was
      necessary for Iranian newborns or not and also what the symptoms of this disease
      before or after diet were. METHODS: The data were collected from 24000 newborn
      babies from Fars Province, southern Iran. The enzymatic calorimetric test was
      done on their blood and Red questions from the children's parents. For treatment,
      free lactose milk or soya milk have been used for the feeding of the newborns.
      RESULTS: The prevalence of galactosemia in Fars Province was 5:24000 in neonates,
      being more than those reported among the white race are and Asians are. The
      maximum clinical symptoms before diet in 10 days after birth were vomiting and
      jaundice and those after using diet were sepsis, full fontanels, and hepatic
      failure. CONCLUSION: Consanguineous marriage is a major cause of inheritance of
      the disease in Iran. The number of familial marriage in children's parents was
      very high. Screening should be executed for all of the families with a history of
      Galactosemia in Iran. To the best of our knowledge, this is the first large study
      report on the prevalence of Galactosemia in Iran.

PMID- 23113109
TI  - The Effect of Aqueous Garlic Extract on Interleukin-12 and 10 Levels in
      Leishmania major (MRHO/IR/75/ER) Infected Macrophages.
AB  - BACKGROUND: The aim of the present study was to investigate the immunomodulation
      effects of aqueous garlic extract (AGE) in the cultured macrophages infected by
      Leishmania major. METHODS: After J774 macrophages proliferation in RPMI1640 and
      incubation with Leishmania for 72 hours, AGE was added in doses of 9.25, 18.5,
      37, 74 and 148 mg/ml for 18, 24 and 48 hours and cell culture supernatants were
      harvested. The Leishmania infected J774 cells to assess the cell viability was
      examined using trypan blue and methylthiazol tetrazolium assay (MTT). An enzyme
      linked immunosorbent assay (ELISA) was performed on cell culture supernatants for
      measurement of interleukin IL-10 and IL-12. RESULTS: Dose of 37 mg/ml for 48
      hours of garlic extract was the most potent dose for activation of amastigotes
      infected macrophages. In addition, AGE increased the level of IL-12 in Leishmania
      infected cell lines significantly. CONCLUSIONS: AGE treated cell is effective
      against parasitic pathogens, and AGE induced IL-12 differentially affected the
      immune response to invading Leishmania parasites.

PMID- 23113110
TI  - Presence of atrazine in the biological samples of cattle and its consequence
      adversity in human health.
AB  - BACKGROUND: Cattle can be considered as an important source for herbicides
      through nutrition. Therefore, herbicide residue in animal products is a potential
      human exposure to herbicides causing public health problems in human life.
      Triazines are a group of herbicides primarily used to control broadleaf weeds in
      corn and other feed ingredients and are considered as possible human carcinogens.
      To evaluate trace residue of these pollutants molecular imprinted solid phase
      extraction (MISPE) method has been developed, using biological samples. METHODS:
      Blood samples were taken from the jugular vein of 45 Holstein cows in 3
      commercial dairy farms in Khuzestan Province, Iran. Urine samples were also taken
      from the cows. RESULTS: The mean +/- SD concentrations of atrazine in serum and
      urine samples of the study group (0.739 +/- 0.567 ppm and 1.389 +/- 0.633 ppm,
      respectively) were higher (P < 0.05) than the concentrations in serum and urine
      samples of the control group (0.002 +/- 0.005 ppm and 0.012 +/- 0.026 ppm,
      respectively). CONCLUSION: Atrazine in the feed ingredients ingested by cattle
      could be transferred into the biological samples and consequently can be
      considered as a potential hazard for the public health.

PMID- 23113111
TI  - Removal of malathion insecticide from water by employing acoustical wave
      technology.
AB  - BACKGROUND: Organophosphorus pesticides are one of the most prevalent usages for
      pest control in the country. Such pesticides enter into water sources by
      different routes. Since drinking of contaminated water at the higher doses than
      the standard level, may causes undesirable effects to human health and ecosystem.
      The object of this research was to investigate the effect of various parameters
      including time, power and concentration on sonodecomposition of malathion
      insecticide in the water. METHODS: The sonochemical degradation of malathion was
      investigated using acoustic wave technology (AWT). AWT with 130 kHz was used to
      study the decomposition of insecticide solution. Samples were analyzed using HPLC
      at different intervals times. Effectiveness of AWT at different times (20, 40,
      60, 80, 100, and 120 minutes), concentrations of malathion at 2, 4 and 8 mg/L as
      well as powers of device (300W, 400W, 500W) are compared. RESULTS: These findings
      showed that the degradation of the malathion insecticide at lower concentrations
      was greater in comparison to higher concentrations. Also, there was positive
      correlation between power increasing and the ability to malathion degradation
      CONCLUSION: The sonodegradation of malathion at different concentrations and
      powers was successfully achieved. It has been shown that acoustical wave
      technology can be used to reduce the concentration of dissolved insecticide using
      high frequency.

PMID- 23113112
TI  - Share of Nations in 37 International Public Health Journals: An Equity and
      Diversity Perspective towards Health Research Capacity Building.
AB  - BACKGROUND: This paper contributes to further exploration of inequity in access
      to health research capacity development by examining the representation of
      different nations in international public health journals. It also aims to
      examine the degree of diversity that exists in these journals. METHODS: This
      study is a descriptive survey. It was done with objective sampling on 37 ISI
      health journals on October of 2008. The number and nationality of people in
      different editorial positions of the journals was identified. The second analysis
      involved recalculating the numbers obtained for each nation to the population
      size of nations per million inhabitants. In order to better compare countries in
      terms of presence in editorial team of the journals, a 'public health editor
      equity gap ratio' (PHEEGR) was developed. RESULTS: Low income countries have
      occupied none of the leadership positions of chief editor or associate /assistant
      chief editors and middle income countries at maximum shared less than 5 percent.
      The PHEEGR gap in access to the different editorial positions between highest to
      the lowest representation of countries was 16/1 for chief editors, 12/1 for
      associate editors, 335/1 for editorial boards and 202/1 for associate editorial
      boards. However, after normalizing the data to the country's population, the gap
      increased significantly. CONCLUSION: There is an imbalance and possibly even
      inequity in the composition of editorial boards and offices of international
      health journals that should be paid significant attention. This can contribute to
      fill the equity gap exists between health in developing and developed countries.

PMID- 23113113
TI  - Detection of Borrelia persica Infection in Ornithodoros tholozani Using PCR
      Targeting rrs Gene and Xenodiagnosis.
AB  - BACKGROUND: Relapsing fever caused by Borrelia persica, is an acute tick-borne
      disease which is transmitted by soft ticks of Ornithodoros tholozani to human.
      METHODS: Value of PCR and xenodiagnosis for detection of B. persica in O.
      tholozani ticks was compared. Sixty-four Borrelia-free ticks were fed on infected
      guinea pigs and used for the experiments. For xenodiagnosis, a group of 32 ticks
      in subsequent blood meal were fed on sterile guinea pigs and the indication of B.
      persica in the animal blood was tested 5-14 days later by dark-field microscopy.
      For PCR, all 64 ticks were subjected to PCR against B. persica rrs gene (16S
      rDNA). Also sensitivity of PCR in terms of minimum detectable number of
      spirochetes as well as the effects of tick sex and post digestion was tested.
      RESULTS: PCR revealed B. persica DNA in 98.4% ticks, in which B. persica were
      found in 25.0% by xenodiagnosis. PCR was enough sensitive to give positive
      results for DNA of 1 spirochete. PCR success rates were similar for male or
      female ticks. Course of time did not affect the efficacy of PCR and similar
      results were observed for ticks of immediately fed, semi- or completely gravid or
      completely digested blood ones. CONCLUSION: Our results indicate that due to very
      low specificity and time consuming, xenodiagnosis is not a useful method whereas
      PCR method has advantages for study the Borrelia prevalence in ticks.

PMID- 23113114
TI  - Patients' Perspectives on Factors that Influence Diabetes Self-Care.
AB  - BACKGROUND: Although diabetes mellitus is of high concern in Iran, and the level
      of control is unacceptable, few qualitative studies have been carried out to
      reflect the experiences of patients on the barriers and motivators to self-care.
      This study aimed to explore a culturally based experience of Iranian diabetic
      patients regarding the personal and environmental barriers to and facilitating
      factors for diabetes self-care. METHODS: Six focus groups were conducted among
      type 2 diabetic patients in the Charity Foundation for Special Diseases' diabetes
      clinic. Purposeful sampling was used. Newly diagnosed patients (less than six
      months) and all type 1 diabetic patients were excluded. Three focus groups were
      held on for each sex. A total of 43 patients participated in the study. Frame
      work analysis was used to extract the themes from the data. RESULTS: DATA
      ANALYSIS SHOWED FIVE MAIN BARRIERS: physical barriers (such as physical effects
      of diabetes); psychological barriers (such as health beliefs); educational
      barriers (such as lack of knowledge about diabetes); social barriers (such as
      group pressure); and care system barriers (such as service availability). Along
      with the barriers, there were some motivators that the participants mentioned as
      a stimuli to control their diabetes. They include beliefs about diabetes,
      perceived responsibility for family, religious beliefs, and the views of
      significant others. CONCLUSION: Culturally based interventions are needed to
      improve diabetes care management in Iran. In addition to personal factors,
      diabetes health educators should pay attention to the environmental factors when
      they develop programs.

PMID- 23113115
TI  - Dearth of a nationwide primary school matriculation dental screening in iran: a
      recall to think.

PMID- 23113116
TI  - Epidemiology and Risk Analysis of Malaria among Pregnant Women.
AB  - Malaria remains a complex problem during the pregnancy, which threatens > 35
      millions pregnant women every year. Malaria pathogenesis in pregnancy results in
      accumulation of infected RBCs in the intervillous spaces causing severe
      alterations leading to the reduced materno-foetal exchanges. In this article we
      have revisited the current evidences of clinical implications and overall burden
      of malaria in pregnancy. Many adverse aftermaths including, low birth weight,
      intrauterine growth retardation, preterm delivery, stillbirth and anemia were
      found associated with malaria in pregnant women. Despite of worldwide
      comprehensive control programmes for malaria in pregnancy, the disease control
      has been a daunting task everywhere. Socio cultural, economical, lack of
      awareness and various logistic problems compound the disease in developing
      countries. Thorough evidence based information and estimates, education and
      awareness and strengthening of prevention programmes are needed urgently to
      achieve success in malaria control in pregnancy.

PMID- 23113117
TI  - Family history and prior allergies of cancers and the risk of adult leukemia in
      shandong province, china.
AB  - BACKGROUND: A case-control study was carried out to investigate the roles of
      prior allergies and family history of cancers and their interaction in the
      etiology of adult leukemia. METHODS: Prior allergies status and family history of
      cancers in first-degree relatives were compared between 131 incident leukemia
      cases and 206 hospital-based controls. Odds ratios (OR) were estimated using an
      unconditional regression model taking into account potential confounding factors.
      RESULTS: Significant association between adult leukemia and prior allergies and
      family history of cancer (OR=2.09, 95% CI: 1.22-3.58 for prior allergies; and
      OR=2.35, 95% CI: 1.09-5.03 for family history of cancer, OR=15.88, 95% CI: 1.77
      142.55 for both the two factors (+), respectively) was found after adjusting for
      potential confounding factors. CONCLUSION: Prior allergies and family history of
      cancers may be risk factors for adult leukemia; their interaction was likely to
      be synergistic rather than additive for the risk of leukemia.

PMID- 23113118
TI  - Long Absence from Work Due to Sickness among Psychiatric Outpatients in Japan,
      with Reference to a Recent Trend for Perfectionism.
AB  - BACKGROUND: Sick leave from work due to psychiatric disorders is a major public
      health problem, not only in Japan but also worldwide. As males and females in
      Japan tend to differ in their approach to work, a gender difference in
      perfectionism might be expected. We investigated the background factors leading
      to long-term absence from work due to sickness among psychiatric outpatients in
      Japan. METHODS: We surveyed 73 psychiatric outpatients who were absent from work
      for a long time (POAWs) and 228 employees without long-term sickness absence as
      controls. GHQ-30, NEO-FFI, MPS, RSS and questionnaires inquiring about background
      factors, including relationships with others, was used, and the data were
      compared between males and females. RESULTS: Male POAWs had a significantly
      higher tendency for depression and perfectionism than the controls, but in
      females this difference was not significant. With regard to personal
      relationships of POAWs, males had worse relationships with superiors and
      colleagues, whereas females had worse relationships with superiors, colleagues,
      and family. CONCLUSIONS: The data suggested that male workers exhibiting
      perfectionism tend to undertake too much work and become exhausted when trying to
      cope with complex human relationships in the workplace. Female workers having the
      double burden of family commitment and perfectionism tend to be isolated in terms
      of personal relationships, leading to exhaustion both in and outside the
      workplace.

PMID- 23113119
TI  - Gender Differences in the Attitude and Strategy towards Weight Control among
      Government Employees in Penang, Malaysia.
AB  - BACKGROUND: This was a cross-sectional study on the gender differences in weight
      control behavior. The strategies used, weight status, weight satisfaction, and
      proportion of individuals attempting to lose weight among 233 government
      employees (104 men and 129 women) working in the Federal Government Building in
      Penang, Malaysia, were assessed. METHODS: Anthropometric indicators such as body
      mass index, waist-to-hip ratio, and body fat percentage were measured to
      determine the subjects' body weight status. A questionnaire covering the
      following items was used to assess weight-control behavior: social support, self
      monitoring, self-efficacy, outcome expectations, planning, preparation/buying,
      portion control, social interactions, and cognitive behavioral strategies.
      RESULTS: About 50% of the subjects were classified as overweight. Based on
      percent body fat percentage, 70% of them were classified as having unhealthy
      levels of body fat. Women were found to be more dissatisfied with their current
      weight, and were more likely to attempt weight reduction compared to men. Women
      reported higher levels of social support for dieting and had better expectations
      for diet and exercise (P < 0.05). They also reported higher use of weight control
      strategies. For self-monitoring, although no gender-dependent differences (P >
      0.05) were observed, women reported more frequent self-monitoring of diet,
      whereas men reported more frequent self-monitoring of exercise. CONCLUSION:
      Health care professionals and researchers should be aware of the different
      strategies used by men and women in order to plan and/or implement community-wide
      weight management programmes.

PMID- 23113120
TI  - Serum Survivin and TP53 Gene Expression in Children with Acute Lymphoblastic
      Leukemia.
AB  - BACKGROUND: The aim of this study was to detect the prognostic significance of
      survivin level and the expression of total p53 in acute lymphoblastic leukemia
      (ALL) and its correlation to patients' outcome. METHODS: Sixty two children newly
      diagnosed with acute lymphoblastic leukemia were treated with chemotherapy and
      followed up for 2 years or until death. Twenty apparently healthy volunteers with
      matched age and sex were taken as control. Survivin protein was measured by
      quantitative sandwich enzyme immunoassay and total human p53 was measured by Flow
      cytometry in peripheral blood at diagnosis and at complete remission. RESULTS: A
      highly significant elevation (P<0.0001) was found in survivin protein and total
      p53 levels in acute lymphoblastic leukemia children patients at diagnosis
      compared to controls. At complete remission a significant decrease of the two
      indices were found in ALL patients compared to those at diagnosis (P<0.0001).
      Survivin protein and total p53 was significantly higher in non-survived compared
      to survived group (P<0.0001 & P=0.016, respectively). A positive correlation was
      found between survivin level and total human p53 level in children with ALL
      (r=0.501 & P<0.0001).  CCONCLUSION: survivin protein is related to anti-apoptotic
      proteins and its high expression lead to unsuccessful treatment of ALL. Survivin
      and TP53 are new prognostic tools in ALL, independent of age and sex.

PMID- 23113121
TI  - Association between Insulin Resistance, Metabolic Syndrome and Nonalcoholic Fatty
      Liver Disease in Chinese Adults.
AB  - BACKGROUND: The aim of this study was to assess the association between insulin
      resistance, metabolic syndrome and nonalcoholic fatty liver disease (NAFLD) in
      Chinese adults. METHODS: Fifty five subjects with NAFLD and 55 controls were
      enrolled for the study. Waist circumference, blood pressure, plasma triglyceride,
      high density lipoprotein cholesterol and fasting plasma glucose concentrations
      and homeostasis model assessment of insulin resistance (HOMA-IR) values as an
      index used to quantify insulin resistance were measured and analyzed. Logistic
      regression was analyzed to predict independent risk factors of NAFLD. RESULTS:
      The prevalence of metabolic syndrome in NAFLD group was obviously higher than in
      controls group (47.3% VS 3.6%, P<0.001). There were all significant differences
      of each component of metabolic syndrome and HOMA-IR values in comparison of
      nonalcoholic fatty liver disease (NAFLD) and controls group. In a logistic
      regression analysis, age, diastolic blood pressure, waist circumference and HOMA
      IR were the covariates independently associated with the presence of NAFLD (Odds
      Ratio=1.107, 1.083, 1.218 and 16.836; 95% CI: 1.011~1.211, 1.001~1.173,
      1.083~1.370 and 3.626~78.168, respectively; P<0.05) CONCLUSION: NAFLD was closely
      associated with metabolic syndrome and insulin resistance was a very strong
      predictor of NAFLD.

PMID- 23113122
TI  - Impacts of earthquake aftermath on indoor carbon monoxide levels in Turkish
      coffeehouses environment in duzce, Turkey.
AB  - BACKGROUND: In 1999, Duzce suffered two consecutive devastating earthquakes above
      magnitude 7 in August and November. In the present study, we aimed to evaluate
      the indoor air quality of coffeehouses by determining carbon monoxide (CO) levels
      and their contributing factors in coffeehouses built before and after the
      earthquake. METHODS: We conducted our study in 76 Turkish coffeehouses in Duzce
      in winter (November 2007-March 2008) during rush hours (18:00-23:00). The Turkish
      coffeehouses included in the study were evaluated under four categories based on
      smoking status and construction date. The characteristics of the coffeehouses,
      such as their CO levels and temperatures both indoors and outdoors, were all
      measured. These analyses were carried out with the SPSS 15.0 program. RESULTS:
      The CO levels in Turkish coffeehouses were above the values indicated as being
      safe by the WHO. While stoves and cooking equipment were determined to contribute
      to indoor CO levels, cigarettes were found to be the main source. Indoor CO
      levels at second hour were very strongly correlated (r: 0.84, P<0.001) (r: 0.91,
      P<0.001) with indoor CO levels at initial and first hour as well as with smoking
      status (r: 0.69, P<0.001); they were also moderately correlated with the room
      volume (r: 0.34, P<0.001) and construction materials (r: 0.31, P<0.001) of the
      coffeehouse. CONCLUSION: Elevated CO levels in Turkish coffeehouses indicate the
      possible presence of other pollutants, particularly when the main source is
      smoking. In such cases, both individuals and the whole of society are affected
      negatively in many ways. Therefore, smoking should be prohibited by law in
      Turkish coffeehouses and national awareness programs should be developed based on
      peoples' lifestyles. Moreover, the standards for construction and management of
      Turkish coffeehouses should be improved as well.

PMID- 23113123
TI  - The -514C/T Polymorphism of Hepatic Lipase Gene among Iranian Patients with
      Coronary Heart Disease.
AB  - BACKGROUND: The T allele of the hepatic lipase (HL) C-514T polymorphism was
      previously found to be associated with lower plasma HL activity. Here, we
      examined the association between this polymorphism and plasma HDL-cholesterol
      concentrations in patients with coronary arteries stenosis. METHODS: We studied
      342 subjects undergoing coronary angiography in two groups of non CAD (n=146) and
      CAD (n=196). -514C->T polymorphism was determined using polymerase chain reaction
      and restriction fragment length polymorphism (PCR-RFLP). RESULTS: After
      adjustment for age, smoking and body mass index, HDL-cholesterol concentrations
      were significantly higher in men with the C/T&T/T genotype than those with the
      C/C genotype(mean 38.6 and 34.7 respectively P=0.01). The frequency of T allele
      in non CAD was 0.136 and 0.226 in female and male respectively and 0.170 and
      0.223 for female and male in CAD subjects. There was no difference in T allele
      frequency in CAD and none CAD groups in male and female (P=0.466 and 0.722
      respectively). CONCLUSION: -514C->T of LIPC gene have a positive effect on HDL-C
      concentration especially in male gender. However, no difference was determined in
      frequency of T allele between CAD and normal arteries subjects.

PMID- 23113124
TI  - Prevention of Disease Complications through Diagnostic Models: How to Tackle the
      Problem of Missing Data?
AB  - BACKGROUND: Diagnostic models are frequently used to assess the role of risk
      factors on disease complications, and therefore to avoid them. Missing data is an
      issue that challenges the model making. The aim of this study was to develop a
      diagnostic model to predict death in HIV/AIDS patients when missing data exist.
      METHODS: HIV patients (n=1460) referred to Voluntary Consoling and Testing Center
      (VCT) of Shiraz southern Iran during 2004-2009 were recruited. Univariate
      association between variables and death was assessed. Only variables which had
      univariate P< 0.25 were selected to be offered to the Multifactorial models.
      First, patients with missing data on candidate variables were deleted (C-C
      model). Then, applying Multivariable Imputation via Chained Equations (MICE),
      missing data were imputed. Logistic regression was fitted to C-C and imputed data
      sets (MICE model). Models were compared in terms of number of variables retained
      in the final model, width of confidence intervals, and discrimination ability.
      RESULT: About 22% of data were lost in C-C model. Number of variables retained in
      the C-C and MICE models was 2 and 6 respectively. Confidence Intervals (C.I.)
      corresponding to C-C model was wider than that of MICE. The MICE model showed
      greater discrimination ability than C-C model (70% versus 64%). CONCLUSION: The C
      C analysis resulted to loss of power and wide CI's. Once missing data were
      imputed, more variables reached significance level and C.I.'s were narrower.
      Therefore, we do recommend the application of the imputation method for handling
      missing data.

PMID- 23113125
TI  - National strategies of ophthalmic education in iran.
AB  - BACKGROUND: Academic medicine is in a state of dramatic transformation. For this
      reason strategic thinking is the most essential part of educational planning. The
      main purpose of the present study was developing the strategic educational
      planning of Ophthalmology in Iran from 2007 to 2010 METHODS: A qualitative
      investigation using focus group discussion has been implemented successfully for
      developing educational planning. Six to twelve representatives of key
      stakeholders in the ophthalmic education of Iran participated to this study.
      RESULTS: Strengths, weaknesses, opportunities and threats of ophthalmology
      education in Iran were analyzed. Strategic goals in education, research, and
      health service providing domains were being developed. Educational goals were
      defined as training of human resources in accordance with the community needs at
      the level of general practitioner, specialist, and fellowships in ophthalmology.
      Research goals of the program were defined as scientific inter-departmental and
      international communications, in order to promote the level of education,
      research, and treatment in the country. Also, in the field of health services
      according to the community needs, providing services by the means of advanced and
      cost effective methods were defined as strategic objectives. CONCLUSION: Based on
      this strategic plan in the last three years ophthalmic education in Iran shall be
      many changes in educational, research and health care provision for social
      accountability.

PMID- 23113126
TI  - Cloning, Expression and Characterization of Zebra Fish Ferroportin in Hek 293T
      Cell Line.
AB  - BACKGROUND: Ferroportin (Fpn), a regulator of iron homeostasis is a conserved
      membrane protein that exports iron across the enterocytes, macrophages and
      hepatocytes into the blood circulation. Fpn has also critical influence on
      survival of microorganisms whose growth is dependent upon iron, thus preparation
      of Fpn is needed to study the role of iron in immunity and pathogenesis of
      micoorganisms. METHODS: To prepare and characterize a recombinant ferroportin,
      total RNA was extracted from Indian zebrafish duodenum, and used to synthesize
      cDNA by RT-PCR. PCR product was first cloned in Topo TA vector and then subcloned
      into the GFP expression vector pEGFP-N1. The final resulted plasmid (pEGFP-ZFpn)
      was used for expression of Fpn-EGFP protein in Hek 293T cells. RESULTS: The
      expression was confirmed by appearance of fluorescence in Hek 293 T cells.
      Recombinant Fpn was further characterized by submission of its predicted amino
      acid sequences to the TMHMM V2.0 prediction server (hidden Markov model),
      NetOGlyc 3.1 and NetNGlyc 3.1 servers. The obtained Fpn from indian zebrafish
      also contained eight transmembrane domains with N- and C-termini inside the
      cytoplasm and harboured 78 O-glycosylated amino acids. CONCLUSION: The
      recombinant Fpn from Indian zebra fish was successfully expressed in Hek 293 cell
      line. Although the discrepancy in two amino acids was observed in our produced
      Fpn and resulted in an additional O-glycosylation site, but had no effect on the
      topology of the protein compared to other Fpn described by other researchers.
      Therefore this construct can be used in future iron studies.

PMID- 23113127
TI  - Multiple Imputation to Deal with Missing Clinical Data in Rheumatologic Surveys:
      an Application in the WHO-ILAR COPCORD Study in Iran.
AB  - BACKGROUND: The aim of the article is demonstrating an application of multiple
      imputation (MI) for handling missing clinical data in the setting of
      rheumatologic surveys using data derived from 10291 people participating in the
      first phase of the Community Oriented Program for Control of Rheumatic Disorders
      (COPCORD) in Iran. METHODS: Five data subsets were produced from the original
      data set. Certain demographics were selected as complete variables. In each
      subset, we created a univariate pattern of missingness for knee osteoarthritis
      status as the outcome variable (disease) using different mechanisms and
      percentages. The crude disease proportion and its standard error were estimated
      separately for each complete data set to be used as true (baseline) values for
      percent bias calculation. The parameters of interest were also estimated for each
      incomplete data subset using two approaches to deal with missing data including
      complete case analysis (CCA) and MI with various imputation numbers. The two
      approaches were compared using appropriate analysis of variance. RESULTS: With
      CCA, percent bias associated with missing data was 8.67 (95% CI: 7.81-9.53) for
      the proportion and 13.67 (95% CI: 12.60-14.74) for the standard error. However,
      they were 6.42 (95% CI: 5.56-7.29) and 10.04 (95% CI: 8.97-11.11), respectively
      using the MI method (M=15). Percent bias in estimating disease proportion and its
      standard error was significantly lower in missing data analysis using MI compared
      with CCA (P< 0.05). CONCLUSION: To estimate the prevalence of rheumatic disorders
      such as knee osteoarthritis, applying MI using available demographics is superior
      to CCA.

PMID- 23113128
TI  - Prevalence and associated factors of insomnia syndrome in the elderly residing in
      kahrizak nursing home, tehran, iran.
AB  - BACKGROUND: As insomnia is common, especially among the elderly in the nursing
      homes, we aimed to estimate insomnia prevalence among the elderly residing in
      nursing homes as well as to determine factors associated with insomnia in the
      elderly. METHODS: This cross-sectional study was carried out in 2009 on 772
      elderly residents at Kahrizak Nursing Home, Tehran Iran. The information was
      gathered through 5-part questionnaires by interviewing either the individuals or
      the nurses in charge and also reviewing the subjects' medical files. Eventually,
      the necessary data were analyzed using oneway ANOVA and Chi-square tests.
      RESULTS: The mean age of the participants was 76.8 +/- 8.05 years (range, 65 to
      107 years). Based on the results, 303 (39.2%) of the elderly, including 86
      (34.7%) men and 217 (41.1%) women, had insomnia syndrome. 433 (56.1%)
      participants complained of difficulty initiating sleep, 357 (46.2%) of disrupted
      sleep, 362 (46.9%) of early morning awakening, and 313 (40.5%) of non-restorative
      sleep. Our findings also showed that age (P = .004), number of diseases (P =
      .019), motility status (P = .017), sleep environment satisfaction (P < .001),
      cognitive status (P = .023), and functional autonomy (P = .003) were
      significantly associated with insomnia. CONCLUSION: Insomnia is a prevalent
      disorder amongst the nursing home elderly population, especially elderly women,
      and several pharmaceutical and nonpharmaceutical factors may trigger its
      occurrence. However, to prevent this problem, further studies are required in
      Iran and Middle Eastern region to establish a reliable understanding about
      insomnia patterns, causes, and cures.

PMID- 23113129
TI  - Level changes of traffic noise in kerman city, southeast iran.
AB  - BACKGROUND: The purpose of this research was to determine the traffic noise level
      and changes in the Kerman City, southeast Iran in recent years. METHODS: This
      cross-sectional study was carried out in 2008 to investigate the existing noise
      situation in Kerman. Sound levels (L(Max), L(Min), L(eq), L(99), L(90), L(50) and
      L(10)) were determined throughout 13 stations using sound level measurement
      system (model, CEL-440). Number of passing vehicles was also assessed at the
      sampled stations. RESULTS: Sound level in all sampled stations was higher than
      Iran and World Health Organization guidelines. Comparison of L(eq) in different
      hours using statistical tests showed significant difference between different
      hours with 95 % confidence coefficient (P=0.01). Comparison of L(eq) throughout
      the week also showed that there was a significant difference (P=0.001) between
      Friday and workday. The comparison of L(eq) with the number of passing vehicles
      using Pearson correlation statistical test showed significant difference between
      the number of heavy vehicles passed and the level of L(eq) (P=0.001). It also
      showed that number of heavy vehicles caused the most noise levels. CONCLUSION:
      The results of this study compared to a similar study conducted in 1999 showed an
      increasingly high noise level. Noise level increased from 1999 to 2008 by 3.89 %
      which is indicative of an increase in noise emission sources.

PMID- 23113130
TI  - Cigarette smoking in iran.
AB  - BACKGROUND: Cigarette smoking is the largest preventable cause of death
      worldwide. No systematic review is available on the situation of the smoking in
      Iran, so we decided to provide an overview of the studies in the field of smoking
      in Iranian populations. METHODS: Published Persian-language papers of all types
      until 2009 indexed in the IranMedex (http://www.iranmedex.com) and Magiran
      (http://www.magiran.com). Reports of World Health Organization were also searched
      and optionally employed. The studies concerning passive smoking or presenting the
      statistically insignificant side effects were excluded. Databases were searched
      using various combinations of the following terms: cigarette, smoking, smoking
      cessation, prevalence, history, side effects, and lung cancer by independent
      reviewers. All the 83 articles concerning the prevalence or side effects of the
      smoking habit in any Iranian population were selected. The prevalence rate of
      daily cigarette smoking and the 95% confidence interval as well as smoking health
      risk associated odds ratio (OR) were retrieved from the articles or calculated.
      RESULTS: The reported prevalence rates of the included studies, the summary of
      smoking-related side effects and the ORs (95%CI) of smoking associated risks and
      the available data on smoking cessation in Iran have been shown in the article.
      CONCLUSION: Because of lack of certain data, special studies on local pattern of
      tobacco use in different districts, about the relationship between tobacco use
      and other diseases, especially non communicable diseases, and besides extension
      of smoking cessation strategies, studies on efficacy of these methods seems to be
      essential in this field.

PMID- 23113132
TI  - Reference charts for height and weight of school children from west malaysia in
      comparison with the United States centers for disease control and prevention.
AB  - BACKGROUND: Reference charts are widely used in healthcare as a screening tool.
      This study aimed to produce reference growth charts for school children from West
      Malaysia in comparison with the United States Centers for Disease Control and
      Prevention (CDC) chart. METHODS: A total of 14,360 school children ranging from 7
      to 17 years old from six states in West Malaysia were collected. A two-stage
      stratified random sampling technique was used to recruit the subjects. Curves
      were adjusted using Cole's LMS method. The LOWESS method was used to smooth the
      data. RESULTS: The means and standard deviations for height and weight for both
      genders are presented. The results showed good agreement with growth patterns in
      other countries, i.e., males tend to be taller and heavier than females for most
      age groups. Height and weight of females reached a plateau at 17 years of age;
      however, males were still growing at this age. The growth charts for West
      Malaysian school children were compared with the CDC 2000 growth charts for
      school children in the United States. CONCLUSION: The height and weight for males
      and females at the start of school-going ages were almost similar. The comparison
      between the growth charts from this study and the CDC 2000 growth charts
      indicated that the growth patterns of West Malaysian school children have
      improved, although the height and weight of American school children were higher
      than those for West Malaysian school children.

PMID- 23113131
TI  - Relationship between Serum Aminotransferase Levels and Metabolic Disorders in
      Northern China.
AB  - BACKGROUND: Increasing evidence suggests an association between elevated serum
      aminotransferase levels and metabolic disorders (metabolic syndrome, hyperlipemia
      and diabetes mellitus). However, the significance of relatively low levels of
      aminotransferases in relation to metabolic disorders has not been fully
      investigated in the general population. We investigated the association between
      serum amiontransferase levels and metabolic disorders using data from a survey in
      Jilin province, China. METHODS: In 2007, a survey was conducted throughout Jilin,
      China, covering both urban and rural areas. A total of 3835 people, 18 to 79
      years old including 1761 men and 2074 women, underwent real-time ultrasonography,
      blood tests including aspartate aminotransferase and alanine aminotransferase,
      and had interviews with a structured questionnaire. RESULTS: Serum
      aminotransferase levels within the normal range were associated with metabolic
      syndrome independent of age, occupation, cultural and educational level, income,
      body mass index, waist circumference, smoking, and alcohol intake. Compared with
      the lowest level (<20 IU/L), the adjusted odds ratios for ALT levels of 20-29, 30
      39, 40-49 and >50 IU/L were 1.92, 2.50, 2.97, and 3.52 in men, and 1.38, 1.54,
      3.06, and 2.62 in women, respectively. Near-normal serum aminotransferase levels
      associated with hyperlipemia, NAFLD, DM were also found in the study.
      CONCLUSIONS: Normal to near-normal serum aminotransferase levels are associated
      with metabolic disorders. Serum ALT levels of 21-25 IU/L for men, and 17-22 IU/L
      for women are suggested as cutoff levels that detect metabolic disorders
      affecting the liver.

PMID- 23113133
TI  - Health research evaluation and its role on knowledge production.
AB  - BACKGROUND: Knowledge production and evaluation are two important functions of
      health research system (HRS). In this article, we aimed to reveal the correlation
      between evaluation of health research organizations and health knowledge
      production promotion. METHODS: A comprehensive evaluation system was developed to
      evaluate the academic performance of national medical science universities on an
      annual basis. It assess following domains; stewardship, capacity building and
      knowledge production. Measurable indicators for each domain were assigned, a
      'research profile' for each department was provided. In this study, we compared
      the results of annually national Health Research System evaluation findings
      during 2005-2008. RESULTS: The number of scientific articles has been increased
      from 4672 to 8816 during 2005 to 2008. It is mentionable that, the number of
      articles which has been published in indexed data bases has risen too. This fact
      could be related to directed policy for more international publication of
      scientific articles from Iran. The proportion of total articles to the number of
      academic members was 1.14 in 2008, comparing to 0.84 in 2005. It means that this
      proportion have increased about twice (0.7 Vs 0.45) during mentioned time.
      Moreover, other scientific products such as authored books based on domestic
      researches and cited articles in textbooks have increased according to special
      attention to knowledge production by policy makers. CONCLUSION: We conclude that
      Health System Research evaluation could be used as a mean for implementing
      policies and promoting knowledge production.

PMID- 23113134
TI  - Preventing Unnecessary Invasive Cancer-Diagnostic Tests: Changing the Cut-off
      Points.
AB  - BACKGROUND: To determine a cut-off point of tPSA and PSAD to prevent unnecessary
      invasive cancer-diagnosing tests in the community. METHODS: This study was
      performed on 688 consecutive patients referred to our center due to prostatism,
      suspicious lesions on digital rectal examination and/or elevated serum PSA
      levels. All patients underwent transrectal ultrasound guided biopsies and
      obtained PSAD. Serum levels of tPSA and fPSA were measured by chemiluminescence.
      Comparisons were done using tests of accuracy (AUC-ROC). RESULTS: Prostate cancer
      was detected in 334 patients, whereas the other 354 patients were suffering from
      benign prostate diseases. The mean tPSA in case and control groups were 28.32+/
      63.62 ng/ml and 7.14+/-10.04 ng/ml; the mean f/tPSA ratios were 0.13+/- 0.21 and
      0.26+/-0.24 in PCa and benign prostate disease groups; the mean PSAD rates were
      0.69+/-2.24, 0.12+/-0.11, respectively. Statistically significant differences
      were found (P <0.05). Using ROC curve analysis, it was revealed that AUC was 0.78
      for tPSA and 0.80 for f/tPSA. Sensitivity was 71% for the cut-off value of
      7.85ng/ml. For f/tPSA ratio, the optimal cut-off value was 0.13 which produced
      the sensitivity of 81.4% and for PSAD, it was15%. CONCLUSIONS: As this trial is
      different from the European and American values, we should be more cautious in
      dealing with the prostate cancer upon the obtained sensitivity and specificity
      for PCa diagnosis (7.85ng/mL for tPSA, 15% for PSAD and 0.13 for f/tPSA ratio).

PMID- 23113135
TI  - Identification and characterization of anti-platelet antibodies in idiopathic
      thrombocytopenic purpura patients.
AB  - BACKGROUND: The autoimmune disease known as Idiopathic (immune thrombocytopenic
      purpura thrombocytopenic purpura (ITP) is clinically defined by a low numbers of
      platelets in the circulation blood. This study aimed to isolate autoantibodies
      made against the platelet glycoproteins using platelets from healthy volunteers,
      to determine their specificity and further elucidate their effects on platelet
      function. METHODS: This study used a phage display system to recognize Fab anti
      platelet antibodies. Anti-platelet After isolation, the anti-platelet Fab
      expressing phage was characterized by ELISA and Western blotting. The Fab-bearing
      phage pool obtained from five rounds of panning was analysed in order to
      determine its anti-platelet reactivity. Of the phage colonies obtained, 100
      colonies of different sizes were randomly selected for reaction with whole
      platelets, using M13 phage as a negative control. RESULTS: Twelve colonies of
      them had strong reactions against the whole platelet preparation, but only four
      colonies showed substantial reactivity against the lysed platelet preparation
      (lysate). Three of the four colonies showed three bands representing proteins
      with different molecular weights. The fourth colony showed only a single band.
      The final experiment to characterise the protein isolated from the phage library
      was a DNA gel agarose test. CONCLUSION: Each colony showed a DNA band that
      corresponded with the molecular size marker for 5.4 kbase pairs, and this
      suggested the presence of heavy and light antibody chains in the phage.

PMID- 23113136
TI  - Increasing serum troponin I and early prognosis in patients with chest pain or
      angina equivalent symptoms in the emergency department.
AB  - BACKGROUND: The purpose of this research was to determine the relation between
      negative or positive qualitative troponin I test and the short term prognosis of
      patients presenting to emergency department with chest pain or angina equivalent
      symptoms. METHODS: we assessed the qualitative rapid troponin I in patients with
      chest pain or angina equivalent symptoms after at least 4 hours and then we
      followed the patients in 72 hours after presentation for adverse events such as
      death, CCU admission, fatal arrhythmias and heart failure. RESULTS: After
      comparing qualitative troponin I test results and adverse events, we concluded
      that the troponin I was significantly more positive in patients with adverse
      events (i.e. CCU admission, fatal arrhythmias and heart failure) (P=0.031).
      CONCLUSION: A single measurement of rapid qualitative troponin I test can be used
      as a prognostic factor in patients with chest pain or angina equivalent symptoms
      and also as a device for risk stratification of moderate and high risk patients.

PMID- 23113137
TI  - Prevalence of metabolic syndrome in adult population from zahedan, southeast
      iran.
AB  - BACKGROUND: The metabolic syndrome (MES) is associated with a high risk of
      diabetes and cardiovascular disease. The aim of the present study was to
      determine the prevalence of the metabolic syndrome as well as cut-off points for
      waist circumference (WC) for diagnosis of MES in Zahedan, southeast Iran.
      METHODS: Totally, 1802 people (735 men and 1067 women) with metabolic syndrome
      were surveyed according to National Cholesterol Education Program Adult Treatment
      Panel III (NCEP ATP III) and the International Diabetes Federation (IDF) criteria
      as well as obtained WC cut-off points for IDF criteria. RESULTS: The prevalence
      of metabolic syndrome was higher in women than in men. In both sexes the
      prevalence increased with age. The prevalence of metabolic syndrome among 1802
      individuals aged >=19 years according to NCEP ATP III, IDF and IDF -AHA/NHLBI
      were 21.0% (15.4% in male, 24.9% female), 24.8 (20.0% in male, 28.1% in female)
      and 23.3% (19.7% in male, 25.8% in female), respectively. Low HDL-C (60.6%) and
      high WC (43.3%) were the most common components of the metabolic syndrome,
      followed by high triglycerides (32%), elevated glucose (17.1%) and high blood
      pressure (13%). CONCLUSION: Our data shows a high prevalence of MES in Zahedan,
      Southeast Iran, therefore, future health prevention strategies are required for
      the prevention of MES.

PMID- 23113138
TI  - Integrated assessment of air pollution in tehran, over the period from september
      2008 to september 2009.
AB  - BACKGROUND: Air pollution is a major problem in urban?industrial areas, like
      Tehran, and has several impacts on human health. This study aimed at assessing
      concentrations of criteria air pollutants (CO, SO(2), NO(2), O(3), PM(10)) in
      Tehran, extracting patterns of hourly, daily, weekly, and monthly variations of
      concentrations, and making comparisons to National Standards and WHO Guidelines.
      METHODS: Air quality data were taken from Air Quality Control Corporation and 5
      sampling stations (out of 13) were selected for analysis according to data
      availability. Microsoft Excel 2003 was used for data analysis and plotting the
      charts. RESULTS: Patterns of temporal variation (hourly, daily, weekly, and
      monthly) of air pollutant concentrations were extracted. In some cases extracted
      patterns matched with the patterns proposed by other researchers. Pollutant
      concentrations were compared to National Standards and WHO Guidelines and it was
      observed that in most of the days, we exceeded the limit values. CONCLUSION: Air
      pollution in Tehran is quite high and there are many days that we exceed the
      standards; therefore appropriate control strategies are needed. Although the
      number of sampling stations is high enough to be representative of whole city, it
      is proposed that an independent sampling station is setup to check the validity
      of the measurements.

PMID- 23113139
TI  - Survival rate of low and very low birth weight neonates in an Iranian community.
AB  - BACKGROUND: This study aimed to assess the incidence and survival rates of
      neonates weighing less than 2500g for duration of the first 28 days in an Iranian
      community. METHODS: In this prospective longitudinal study, all neonates with
      birth weight less than 2500g were selected from the list of all neonates born in
      the only public-sector referral hospital, for a six months period. The weight of
      neonates at birth along with some demographic variables was recorded on a
      checklist. A cohort of neonates with birth weight less than 2500g were followed
      for 28 days. Mortality within 28 days of birth was used as end point. Continuous
      variables were summarized using mean and 95% confidence intervals, while
      categorical variables were presented as ratios and percentages. RESULTS: About
      1750 neonates were born of which 168 neonates with birth weights less than 2500g
      were recorded giving a proportion of 9.6%. Of 168 neonates, 21 (12.5%) had very
      low birth weights (VLBW) (birth weights<1500g). Survival rates for the groups of
      LBW (1500<birth weights<2500g) and VLBW neonates were 98.4% and 66.6%,
      respectively. Regression analysis showed birth weight has, unsurprisingly, the
      most effect (beta= 0.501) on the survival rate among variables studied in this
      research. CONCLUSION: The survival rate among VLBW births in our study is
      dramatically low (66.6%). Not only attempts must be made to reduce the incidence
      and prevalence of this problem but also we need to work on the related factors of
      neonates' survival rate in this community.

PMID- 23113140
TI  - Measuring Radionuclides Concentration in Rice Field Soils using Gamma
      Spectroscopy in Northern Iran.
AB  - BACKGROUND: A few elements of soil are radioactive. Soil can transfer
      radionuclide into plants feeding human. Sometimes their levels are as high as to
      be concern of human healthy. Rice has an important share for Iranian foods
      especially in north of Iran. Therefore we decided to obtain radionuclides
      concentration emitting gamma rays in Lahijan City (Northern Iran) rice fields
      using gamma spectroscopy. METHODS: Twenty eight samples from rice field's soils
      and 12 samples from superficial soils were collected at a square of 10*10 m2 to
      get 2kg weight. To make dry samples were put into oven at 105 degrees C for 24h.
      Then they were milled and 950 gr of each sample was transferred to Marinelli
      container with 1000(cc) volume, sealed and left for 40 days to get secular
      equilibrium. After measuring Ph, Electric conductivity and organic carbon, gamma
      spectroscopy was done to get sample gamma spectrum at 2000-6000 sec using HpGe
      detector. RESULTS: It was found (226)Ra activity in rice fields of 29.273+/-0.72
      Bqkg-1 and city soil of 31.02+/-1.1 Bqkg-1 and also 232Th activity of 37.47+/
      1.12 Bqkg-1 for rice fields' soils and 40.47+/-1.68 Bqkg-1 for city soil were in
      standard mode. CONCLUSION: (40)K activities mean value according to UNSCEAR; 2000
      was found a little greater than standard. A little value of (137)Cs was found in
      Lahijan rice fields and city soils that could be as a result of Chernobyl
      accident. In except of 137Cs, for three other under studied city soil elements,
      activities were greater than that of rice fields.

PMID- 23113141
TI  - Evaluation of Chronic Hepatitis B Infection in Patients with Seronegative HbsAg.
AB  - BACKGROUND: It is estimated that about 370 million people are chronic carriers of
      HBV worldwide. Apparently 3% of Iranian populations are chronic carriers of this
      virus. We aimed to evaluate the viral DNA in biological fluids of chronic
      hepatitis patients compared to a control group. METHODS: The current case-control
      study was designed to evaluate the viral DNA in biological fluids of 70 chronic
      hepatitis patients compared to a control group using ELISA, PCR and Real Time.
      RESULTS: All individuals (100%) in case group were HBsAg positive while in
      control group only 2 individuals (2.8%) were HBsAg positive. Three individuals,
      in control group were positive using PCR and Real Time PCR indicating that about
      7% of those in control group were chronic carriers of HBV. The interesting point
      was the copy of viral DNA; (5.49 *10(4), 2.162*10(3) and 7.26*10(6)) for 3
      chronic carriers using sera while it was about (5.71*10(3), 1.45*10(2) and
      2.56*10(5)) using ear cerumen confirming the necessity of investigating for the
      carriers of HBV in different biological fluid and by different methods.
      CONCLUSION: It can be concluded chronic carriers of hepatitis B are much more
      than what is diagnosed by routine diagnostic tests. On the other hand ELISA alone
      can not be relied on as a complete test for screening of chronic carriers in
      hepatitis B. PCR and Real Time PCR are more reliable tests for this purpose.

PMID- 23113142
TI  - Prevalence and severity of carpal tunnel syndrome in women.
AB  - BACKGROUND: Carpal tunnel syndrome (CTS) is entrapment of median nerve in carpal
      tunnel of the wrist. The prevalence of CTS related to pregnancy and non-pregnancy
      is unknown in some countries such as Iran. The main aim of this study was to
      determine the prevalence of CTS in women of Boyerahmad Township located in South
      West part of Iran. METHODS: This cross-sectional descriptive analytic study was
      done since February 2010 to January 2011 in Obstetrics and Gynecology clinics in
      2656 non-pregnant and 1508 pregnant women. The women that had clinical symptoms
      of CTS performed standard electro diagnostic techniques for rule in or rule out
      of CTS. RESULTS: The prevalence of CTS in pregnant and non- pregnant women was
      3.4 and 2 .3 percent respectively. The prevalence of CTS in all women was 2.7%.
      Overall, 51 pregnant women had CTS that 59.4% had mild, 18.8 % had moderate and
      21.9% had severe CTS. Sixty-one non-pregnant women had CTS that 73.6 %had mild,
      20.8 %t had moderate and 5.6 % had severe CTS. CONCLUSION: Although the
      prevalence of CTS in Iranian pregnancy is higher than non-pregnancy women
      conservative treatment is safe and more effective.

PMID- 23113143
TI  - Alveolar Echinococcosis Infection in a Monkey (Ateles geoffroyi) In Mashhad,
      Iran.
AB  - Alveolar echinococcosis (AE), which is caused by ingestion of eggs of the fox
      tapeworm Echinococcus multilocularis, is the most potentially lethal parasitic
      infection because of its tendency to invade and proliferate in the liver and the
      difficulty in treatment. This article describes a case of alveolar echinococcosis
      found in Ateles geoffroyi in Mashhad, Iran. The cysts were characterized as an
      alveolar structure, composed of numerous small vesicles in liver, abdominal
      cavity, retroperitoneum and lungs. A characteristic feature of these vesicles was
      its exogenous tumor-like proliferation. These cysts were filled with numerous
      protoscoleces suggesting a potential role of this monkey in cycle of
      transmission. Up to now, this is probably the first report of alveolar
      echinococcosis in A. geoffroyi in the world.

PMID- 23113144
TI  - An overview of the burden of non-communicable diseases in India.
AB  - Non-communicable disease continues to be an important public health problem in
      India, being responsible for a major proportion of mortality and morbidity.
      Demographic changes, changes in the lifestyle along with increased rates of
      urbanization are the major reasons responsible for the tilt towards the non
      communicable diseases. In India, there is no regular system for collecting data
      on non-communicable diseases (NCDs) which can be said to be of adequate coverage
      or quality. Lack of trained health care workers, primary care providers armed
      with inadequate knowledge and skills along with ill-defined roles of various
      health sectors i.e. public, private, and voluntary sectors in providing care have
      played key hurdles in combating the growing burden of non-communicable diseases.
      Empowerment of the community through effective health education, use of trained
      public health personnel along with provision of free health care and social
      insurance would prove beneficial in effectively controlling the growing
      prevalence of NCDs.

PMID- 23113145
TI  - Child mortality rate in ethiopia.
AB  - Ethiopia's childhood mortality has continued to decline although at a swift pace.
      The drop in urban childhood mortality decline, duration of breastfeeding is the
      principle reason for the overall decline in mortality trends in Ethiopia. Data
      from the Ethiopian Demographic and Health Surveys 2000 and 2005 were used.
      Indirect estimation of Brass and Trussell's methods were adopted. Selected
      demographic and socio-economic variables were included in the analysis with
      statistically significant effects. Findings clearly show neonatal and post
      neonatal mortality decline gradually. Even though, Ethiopia's childhood mortality
      rates are still high. The result shows less than 2 years birth interval have
      higher infant mortality rates than higher birth interval (113 deaths per 1000).
      The proper spacing of births allows more time for childcare to make more maternal
      resources available for the care of the child and mother. Therefore, further
      research is urgent for regional level and national level investigation.

PMID- 23113146
TI  - Birth defects data from surveillance hospitals in hubei province, china, 200l -
      2008.
AB  - BACKGROUND: To determine the prevalence and characteristics of birth defects in
      perinatal infants in Hubei Province during 200l-2008. METHODS: The prevalence of
      birth defects in perinatal infants delivered after 28 weeks or more was analyzed
      in Hubei surveillance hospitals during 200l-2008. RESULTS: The incidence of birth
      defects in perinatal infants from 200l to 2008 was 120.0 per 10,000 births, and
      was increased by about 41% from 81. 1 in 2001 to 138.5 per 10,000 births in 2008.
      The incidence in the first 4 years (2005-2008) was much higher than the latter
      four (2001-2004) (chi(2)=77.64, P <0.05). The difference in prevalence between
      urban and rural was of no significance in 2008 (chi(2)=0.03, P >0.05), but that
      between male and female was significant (chi(2)=5.24, P <0.05), as the former
      prevalence was much higher. The prevalence of birth defects was slightly higher
      among mothers over 35 years old than those under 35 years old, but with no
      significance (chi(2)=1.98, P >0.05). The two leading birth defects were cleft lip
      and/or palate and polydactyly, followed by congenital heart disease,
      hydrocephaly, external ear malformation and neural tube defects. The prevalence
      of congenital heart disease was rising. CONCLUSIONS: Eight years' birth defects
      data indicate that the birth defect rate was on the rise and the birth defects
      prevalence in Hubei province should be valued.

PMID- 23113147
TI  - Investigation of the heavy metal contamination of the sediments from the yellow
      river wetland nature reserve of zhengzhou, china.
AB  - BACKGROUND: Heavy metal pollution in the sediment of the Yellow River draws wide
      attention in the recent years. The Yellow River Wetland Nature Reserve of
      Zhengzhou is one of the major wetlands of the river and located at the beginning
      of the lower reach. In this article, we aimed to investigate the degree and the
      sources of the metal pollution in the reserve. METHODS: Metals as Cu, Pb, Cr, Cd
      and Mn in the sediment were monitored using flame atomic absorption spectrometry.
      The index of geo-accumulation (I(geo)) and the modified degree of contamination
      (mC(d)) were developed to evaluate individual metal pollution and overall
      enrichment impact of the elements. RESULTS: Compared with sediment quality
      guidelines, the effect of Cr and Pb are more serious than others. I(geo) values
      show Pb pollution are moderate at the Xinzhai, Langchenggang and Nansutan sites,
      and mC(d) analysis indicate the whole contamination at the Wantan, Langchenggang
      and Nansutan sites was low. Principal component analysis indicated that the first
      factor was Cu, Mn and Cd, mainly from soil erosion and the irrational use of
      phosphate fertilizers; the second Pb from fossil fuel burning; and the third Cr
      from weathering process. CONCLUSION: We conclude that Pb contamination is serious
      in the reserve, and the main sources of the metal are crude oil consumption and
      coal combustion of the brick kilns around. We also draw a conclusion that it is
      vital to evaluate contamination degree with both individual elements and overall
      average.

PMID- 23113148
TI  - Gender differences in the risk of coronary artery disease in iran.
AB  - BACKGROUND: Given gender differences in the risk of coronary artery disease
      (CAD), the present study sought to investigate these dissimilarities amongst
      patients who underwent angiography at a major, tertiary heart hospital in Iran.
      METHODS: Between 2005 and 2010, 44,820 patients who underwent coronary
      angiography were enrolled in a registry. Pre-procedural data such as
      demographics, CAD risk factors, presenting symptoms, and laboratory tests, as
      well as post-procedural data were collected. The data were, subsequently,
      compared between the men and women. RESULTS: Out of the 44,820 patients (16,378
      women), who underwent coronary angiography, 37,358 patients (11,995 women) had
      CAD. Amongst the CAD patients, the females were not only significantly older,
      less educated, and more overweight than were the males but also had higher levels
      of triglyceride, cholesterol, low-density lipoprotein, high-density lipoprotein,
      and fasting blood sugar (P< 0.001). Of all the risk factors, hypertension and
      diabetes mellitus showed the strongest association in our female CAD patients
      (OR=3.45, 95%CI: 3.28-3.61 and OR=2.37, 95%CI: 2.26-2.48, respectively). Acute
      coronary syndrome was more prevalent in the men (76.1% vs. 68.6%, P< 0.001), and
      chronic stable angina was more frequent in the females (31.4% vs. 23.9%, P<
      0.001). With respect to post-procedural recommendations, the frequency of
      recommendations for non-invasive modalities was higher in the females (20.1% vs.
      18.6%, P< 0.001). CONCLUSION: Hypertension and diabetes mellitus had the
      strongest association with CAD in our female patients. In the extensive CAD
      patients, medical treatment was recommended to the women more often.

PMID- 23113149
TI  - Financial burden of health care expenditures: Turkey.
AB  - In this study, we examine whether and to what extent the health insurance system
      in Turkey provided adequate protection against high out of pocket expenditures in
      the period prior to "The Health Transformation Programme". Furthermore, we
      examine the distribution of out of pocket expenditures by demographic
      characteristics, poverty status, health service type, access to health care and
      self-reported health status. We employ the 2002/03 National Household Health
      Expenditure Survey data to analyze financial burden of health care expenditure.
      Following the literature, we define high burdens as expenses above 10 and 20% of
      income. We find that 19% of the nonelderly population were living in families
      spending more than 10% of family income and that 14% of the nonelderly population
      were living in families spending more than 20% of family income on health care.
      Furthermore, the poor and those living in economically less developed regions had
      the greatest risk of high out of pocket burdens. The risk of high financial
      burdens varied by the type of insurance among the insured due to differences in
      benefits among the five separate public schemes that provided health insurance in
      the pre-reform period. Our results are robust to three alternative specifications
      of the burden measure and including elderly adults in the sample population. We
      see that prior to the reforms there were not adequate protection against high
      health expenditures. Our study provides a baseline against which policymakers can
      measure the success of the health care reform in terms of providing financial
      protection.

PMID- 23113150
TI  - Evaluation of culture and PCR methods for diagnosis of group B streptococcus
      carriage in Iranian pregnant women.
AB  - BACKGROUND: Group B streptococcus (GBS) is one of the most important cause of
      morbidity and mortality among newborns especially in developing countries. It has
      been shown that the screening approach rather than the identification of maternal
      clinical risk factors for early-onset neonatal GBS disease is more effective in
      preventing early-onset GBS neonatal disease. The objective of this study was to
      detect GBS among clinical samples of women using PCR and standard microbiological
      culture. METHODS: Samples were taken from 375 women at 28-38 weeks of gestation
      during six month from January 15 till June 15, 2011 from a hospital in Tehran,
      Iran. Samples were tested by standard culture using Todd-Hewitt broth, blood agar
      and by PCR targeting the cfb gene. RESULTS: Among the 375 women, 35 (9.3%) were
      identified as carriers of group B streptococci on the basis of the results of the
      cultures of specimens, compared to 42 (11.2 %) on the basis of PCR assay.
      CONCLUSION: We found that GBS can be detected rapidly and reliably by a PCR assay
      in vaginal secretions from women at the time of delivery. This study also showed
      that the rate of incidence of GBS is high in Iranian women.

PMID- 23113151
TI  - Five-year Evaluation of Chronic Diseases in Hamadan, Iran: 2005-2009.
AB  - BACKGROUND: Now the increasing growth of chronic diseases is the major health
      challenge worldwide. This survey was conducted to assess noncommunicable diseases
      related risk factors. METHODS: A population-based cross sectional study was
      conducted in 2005 and repeated annually by 2009 in Hamadan province, the west of
      Iran using two-stage cluster sampling method. A total sample of 6500 subjects 15
      to 64 years old were enrolled. RESULTS: The total prevalence of cigarette smoking
      was 18% [95% CI 17% to 19%], 35.1% in men versus 1.1% in women. The smokers
      consumed on average 15 cigarettes per day. Almost 26.3% [95% CI 24.8% to 27.7%]
      of the target population eat five or more servings of fruits and vegetables per
      day; 52.8% [95% CI 51.2% to 54.3%] had work related physical activity; 28.1% [95%
      CI 26.7% to 29.4%] had physical activity during leisure time; 80.3% [95% CI 79.0%
      to 81.5%] had transportation related physical activity; 47.2% [95% CI 46.0% to
      48.4%] were either overweight or obese; 8.1% [95% CI 7.1% to 9.2%] had impaired
      fasting blood sugar or were confirmed diabetes; 33.7% [95% CI 31.9% to 35.5%] had
      hypercholesterolemia; and 15.6% [95% CI 13.0% to 18.3%] had hypertriglyceridemia.
      There was a statistically significant association of age and gender with body
      mass index, systolic and diastolic hypertension, hyperglycemia,
      hypercholesterolemia and hypertriglyceridemia. CONCLUSIONS: The evidences of the
      present survey promise a silent progressive epidemic of chronic diseases among
      Iranian citizens that may lead to an increasing growth of noncommunicable
      diseases in the next decade.

PMID- 23113152
TI  - Use of Single-enzyme PCR-restriction Digestion Barcode Targeting the Internal
      Transcribed Spacers (ITS rDNA) to Identify Dermatophyte Species.
AB  - BACKGROUND: Dermatophytes are the most common causative agents of superficial
      mycoses. Species identification of these fungi is important from therapeutic and
      epidemiological point of wive. Traditional approaches for identification of
      dermatophytes at the species level, relying on macroscopic and microscopic
      features of the colonies, usually are time-consuming and unreliable in many
      circumstances. Recently a broad varieties of rapid and accurate DNA-based
      techniques were successfuly utilized for species delineation of dermatophytes.
      METHODS: The ITS1-5.8S-ITS2 region of rDNA from various reference strains of
      dermatophyte species were amplified using the universal fungal primers ITS1 and
      ITS4.The PCR products were digested by a single restriction enzyme, MvaI. The
      enzyme was evaluated in both in silico and practical PCR-RFLP assay to find the
      exact differentiating restriction profiles for each species. To validate the
      standardized PCR-RFLP system, all tested strains were subjected to sequencing and
      sequence analysis. RESULTS: The obtained RFLP patterns were specific for many
      species including T. interdigitale, T. rubrum, T. violaceum, M. persicolor, M.
      audouinii, M. nanum (A. obtusum) and E. floccosum but were similar for some
      closely related species such as M. canis / M. ferrugineum. Sequencing of the ITS1
      5.8S-ITS2 fragment from all type strains affirmed the RFLP findings. CONCLUSION:
      It was practically revealed that the ITS-PCR followed by MvaI-RFLP is a useful
      and reliable schema for identification and differentiation of several pathogenic
      species and can be used for rapid screening of even closely related species of
      dermatophytes in clinical and epidemiological settings.

PMID- 23113153
TI  - Evaluating the efficiency of lettuce disinfection according to the official
      protocol in iran.
AB  - BACKGROUND: The objective of this study was to evaluate the efficacy of
      Sanitization of Lettuce according to the protocols set forth by Iranian Ministry
      of Health and Medical Education for reducing populations of total coliform, fecal
      coliform, and helminth eggs present on lettuce. METHODS: In the present study, we
      determined the load of total coliform, fecal coliform, and parasites of lettuce.
      The lettuce was sanitized by protocol of Iranian Ministry of Health and Medical
      Education. The protocol consists of 3 levels to disinfect the fruits and
      vegetables. The procedure was as follows: first washing stage. The leaves of
      leafy vegetables washed with tap water, second stage, separation of helminth eggs
      by 3 to 5 droplets of detergent per liter for 5 min; third stage, disinfection of
      vegetables by calcium hypochlorite solution (with 200 mg/l free chlorine) for 5
      min; and finally the disinfected vegetables were washed with tap water. RESULTS:
      The average initial levels of total coliform and fecal coliform in the samples
      were 3.36 log(10) cfu/g and 2.31 log(10) cfu/g, respectively. Helminth eggs were
      not detected in any of the samples tested. The efficiency of total coliform and
      fecal coliform removal were 78.1% (0.75 log(10)cfu/g) and 79.6% (0.67
      log(10)cfu/g), respectively, after washing. This increased up to 94.8(1.44
      log(10)cfu/g) and 98.5% (1.90 log(10)cfu/g) after the use of detergent. Chlorine
      disinfection rose these amounts up to 98.3% (2.18 log(10)cfu/g) and 100% (2.31
      log(10)cfu/g), respectively. CONCLUSION: By applying the protocol large parts of
      microorganisms existing on lettuce have indeed been removed.

PMID- 23113154
TI  - Identification of Hepatitis B Virus Surface Antigen (HBsAg) Genotypes and
      Variations in Chronic Carriers from Isfahan Province, Iran.
AB  - BACKGROUND: Hepatitis B virus (HBV) gene and protein variations are frequently
      been seen in chronic patients. The aims of study were to determine the genotypes
      as well as the patterns of variations distribution in chronically-infected
      patients from the central part of Iran. METHODS: The surface gene was amplified,
      sequenced and subsequently aligned using international and national Iranian
      database. RESULTS: All strains belonged to genotype D, subgenotype D1 and subtype
      ayw2. Of all 62 mutations occurred at 39 nucleotide positions, 31 (50%) were
      missense (amino acid altering) and 31 (50%) were silent (no amino acid changing).
      At the amino acid level, 30 substitutions occurred, however, 3 were in positions
      122 and 127, corresponded to subtypic determination. 22 (73%) out of 30 amino
      acid mutations occurred in different immune epitopes within surface protein, of
      which 12 (54.54%) in B cell epitopes in 10 residues; 5 (45.45%) in T helper
      epitopes in positions; 5 (22.73%) in inside CTL epitopes in 4 residues.
      CONCLUSION: The distribution of amino acid mutations as well as the ratio between
      silent and missense nucleotide mutations showed a narrowly focused immune
      pressure had already been on the surface protein in these patients, led to the
      emergence of escape mutants in these patients.

PMID- 23113155
TI  - Novel Mutations in Sandhoff Disease: A Molecular Analysis among Iranian Cohort of
      Infantile Patients.
AB  - BACKGROUND: Sandhoff disease is an autosomal recessive disorder caused by beta
      hexosaminidase deficiency and accumulation of GM2 ganglioside resulting in
      progressive motor neuron manifestations and death from respiratory failure and
      infections in infantiles. Pathogenic mutations in HEXB gene were observed which
      leads to enzyme activity reduction and interruption of normal metabolic cycle of
      GM2 ganglioside in sandhoff patients. METHODS: Six infantile index patients with
      typical biochemical and clinical picture of the disease were studied at the
      molecular level. After DNA extraction and amplification, probands and their
      parents, were evaluated by direct sequencing of amplicons. RESULTS: We identified
      7 different mutations among which 4 were novel. The most prevalent finding (50%)
      among our population was a 16 kb deletion including the promoter and exons 1-5.
      The other findings included c.1552delG and c.410G>A, c.362 A>G, c.550delT,
      c.1597C>T, c.1752delTG. CONCLUSION: We conclude that Cys137Tyr and R533C
      mutations may be pathogenic because of changing amino acid and locating at the
      conserved region and also they have not been observed in hundred controls.
      Besides, four mutations including: Cys137Tyr, c.1552delG, c.1597C>T and c.550delT
      fulfilled almost criteria for pathogenic mutation.

PMID- 23113156
TI  - Infants' Exposure to Aflatoxin M1 from Mother's Breast Milk in Iran.
AB  - BACKGROUND: The occurrence of aflatoxin M1 (AFM1) in milk, especially breast
      milk, is a valuable biomarker for exposure determination to aflatoxin B(1)
      (AFB(1)). In the present study, the risk of exposure to AFM(1) in infants fed
      breast milk was investigated. METHODS: An enzyme-linked immunosorbent assay
      (ELISA) was used for the analysis of AFM(1) in breast milk samples from 132
      lactating mothers referred to four urban Mothers and Babies Care Unit of Hamadan,
      western Iran. RESULTS: AFM(1) was detected in eight samples (6.06%) at mean
      concentration of 9.45 ng/L. The minimum and maximum of concentration was 7.1 to
      10.8 ng/L, respectively. Although the concentration of AFM(1) in none of the
      samples was higher than the maximum tolerance limit accepted by USA and European
      Union (25 ng/kg) however, 25% had a level of AFM(1) above the allowable level of
      Australia and Switzerland legal limit (10 ng/L). CONCLUSIONS: Lactating mothers
      and infants in western parts of Iran could be at risk for AFB(1) and AFM(1)
      exposure, respectively. Considering all this information, the investigation of
      AFM(1) in lactating mothers as a biomarker for post-natal exposure of infants to
      this carcinogen deserves further studies in various seasons and different parts
      of Iran.

PMID- 23113157
TI  - Detection of Extended Spectrum B-Lactamases in Urinary Isolates of Klebsiella
      pneumoniae in Relation to Bla, Bla and Bla Gene Carriage.
AB  - BACKGROUND: Resistance to contemporary broad-spectrum beta-lactam antibiotics
      mediated by extended-spectrum beta-lactamases (ESBLs) is increasing worldwide.
      Klebsiella pneumoniae, an important cause of nosocomial and community acquired
      urinary tract infections has rapidly become the most common ESBL producing
      organism. We examined ESBL production in urinary isolates of K. pneumoniae in
      relation to the presence of bla(SHV), bla(TEM) and bla(CTX-M) genes. METHODS:
      Antibiotic resistance of 51 clinical isolates of K. pneumoniae was determined to
      amoxicillin, amikacin, ceftazidime, cefotaxime, cefteriaxon, ceftizoxime,
      gentamicin, ciprofloxacin and nitrofurantoin by disc diffusion. Minimum
      inhibitory concentrations were also measured for ceftazidime, cefotaxime,
      cefteriaxon, ceftizoxime and ciprofloxacin. ESBL production was detected by the
      double disc synergy test and finally, presence of the bla(SHV), bla(TEM) and
      bla(CTX-M) genes were shown using specific primers and PCR. RESULTS: Disc
      diffusion results showed that 96.08 % of the isolates were resistant to
      amoxicillin followed by 78.43 % resistance to nitrofurantoin, 49.02 % to amikacin
      and ceftazidime, 41.17 % to ceftriaxone, 37.25% resistance to cefotaxime and
      ceftizoxime, and 29.42 % to gentamicin and ciprofloxacin. Both resistant and
      intermediately resistant organisms were resistant in MIC determinations. Twenty
      two isolates (43.14%) carried bla(SHV), 18 (35.29%) had bla(TEM) and 16 (31.37%)
      harbored bla(CTX-M) genes. ESBL production was present in 14 isolates (27.45 %)
      of which, 3 did not harbor any of the 3 genes. Among the non-ESBL producers, 9
      lacked all 3 genes and 2 carried them all. CONCLUSION: No relation was found
      between gene presence and ESBL expression.

PMID- 23113158
TI  - Emporiatrics: the travellers medicine.

PMID- 23113159
TI  - Public health ethics related training for public health workforce: an emerging
      need in the United States.
AB  - BACKGROUND: Ethics is a discipline, which primarily deals with what is moral and
      immoral behavior. Public Health Ethics is translation of ethical theories and
      concepts into practice to address complex multidimensional public health
      problems. The primary purpose of this paper was to conduct a narrative literature
      review-addressing role of ethics in developing curriculum in programs and schools
      of public health, ethics-related instruction in schools and programs of public
      health and the role of ethics in developing a competent public health workforce.
      METHODS: An open search of various health databases including Google scholar and
      Ebscohost yielded 15 articles related to use of ethics in public health practice
      or public health training and the salient features were reported. RESULTS:
      Results indicated a variable amount of ethics' related training in schools and
      programs of public health along with public health practitioner training across
      the nation. Bioethics, medical ethics and public health ethics were found to be
      subspecialties' needing separate ethical frameworks to guide decision making.
      CONCLUSIONS: Ethics based curricular and non-curricular training for emerging
      public health professionals from schools and programs of public health in the
      United States is extremely essential. In the current age of public health
      challenges faced in the United States and globally, to have an ethically
      untrained public health force is arguably, immoral and unethical and jeopardizes
      population health. There is an urgent need to develop innovative ethic based
      curriculums in academia as well as finding effective means to translate these
      curricular competencies into public health practice.

PMID- 23113160
TI  - Effects of Soy on Body Composition: A 12-Week Randomized Controlled Trial among
      Iranian Elderly Women with Metabolic Syndrome.
AB  - BACKGROUND: To examine the effects of soy [in the form of textured soy protein
      (TSP) and soy-nut] on body composition in elderly women with metabolic syndrome
      (MetS). METHODS: A 12-week randomized clinical trial was conducted on 75 women
      between 60-70 years of age with MetS in rural health clinics around Babol, Iran
      in 2009. The participants were randomly assigned to one of the three groups of
      soy-nut (35g/d), TSP (35g/d) and control. Body fat, lean mass and anthropometric
      indicators were measured before and after intervention, too. RESULTS:
      Participants were classified as overweight and showing android fat distribution.
      After 12 weeks of intervention, both soy-nut and TSP groups showed an increase of
      non-significant in lean mass (0.9 and 0.7 kg), hip circumference (0.45 and 0.28
      cm), triceps skinfold (TSF) thickness (0.87 and 0.67mm) and reduction in BMI (
      0.15 and -0.33), waist circumference (-0.83 and -1.2) and body fat (-1.5% and 
      1.7%). Significant increase in the mean change of TSF and lean mass was observed
      in the users of soy-nut compared to the control group (P<0.01, P<0.05).
      CONCLUSION: 12-week intervention of soy had a mild favorable effect on body
      composition in elderly women with MetS.

PMID- 23113161
TI  - The indicators of reproductive behavior in young families as a criterion of the
      social and economic level of the society in Kazakhstan.
AB  - BACKGROUND: In Kazakhstan, as in many other countries, a transformation of the
      traditional stereotypes of reproductive behavior, and change the types of family
      relationships is occurred. It is caused by social status changes, by the
      transformation of women's valuable orientations and social-role attitudes. The
      objective of this study was to identify the indicators of reproductive units and
      the motives for having children in the family. METHODS: Designed questionnaires
      were used to study the regulation of fertility in young families, and women's
      views about the ideal, desired, and expected number of children per family. The
      survey covered 1017 respondents aged less than 39 years. RESULTS: Expected number
      of children in the family depends on living conditions. The average expected
      number of children per family increases with improvement of living conditions and
      with increases in income. Statistically significant differences in the average
      expected number of children in families with a satisfactory and good income
      compared to poor income (P <0.001). Revealed the predominance of the expected,
      desired and ideal number of children among women of Asian ethnic group and on the
      desired and ideal number of children the differences were statistically
      significant (P <0.05). By mathematical formula that based on a poll can be
      calculated probability of birth of each child in the family. CONCLUSION:
      Reproductive attitudes of Astana women depend on age, educational level, income,
      professional employment, marital status, and ethnicity. The findings confirm the
      hypothesis that family plans are largely exposed to specific conditions of life.

PMID- 23113162
TI  - An exploratory analysis of dynamic change of metabolic syndrome in relation to
      the risk of developing cardiovascular disease in a chinese cohort.
AB  - BACKGROUND: Metabolic syndrome (MS) is the syndrome closely related to
      cardiovascular disease (CVD) risk factors. Few prospective studies have compared
      the impact of dynamic changes of MS on the development of cardiovascular diseases
      (CVD). METHODS: Overall, 3461 subjects were recruited from a cohort study on
      Prevention of Multiple Metabolic disorders and MS in Jiangsu of China (PMMJS)
      with a follow up of 3.8 years. The associations between the dynamic changes
      (Difference, the value at first follow-up subtract the value at baseline) of MS,
      component numbers, components and relative risk (RR) of CVD were analyzed by
      using Cox regression model. RESULTS: The total incidence standardized rate of CVD
      was 2.58%,and the incidence standardized rates of CVD in MS-/follow-up MS
      ,baseline MS-/follow-up MS+, baseline MS+/follow-up MS- and baseline MS+/follow
      up groups were 2.05%,5.01%,1.65% and 4.39% separately. After adjustment
      confounding factors Difference in FPG, BP and TG have significantly effects on
      the incidence of CVD. CONCLUSION: Difference of MS component numbers had the
      prediction ability of CVD, but MS groups based on baseline and first follow-up MS
      and/or non-MS had not. In Chinese, the dynamic change of MS component numbers was
      a useful predict factor for CVD.

PMID- 23113163
TI  - Waist Circumference, Weight, and Body Mass Index of Iranians based on National
      Non-Communicable Disease Risk Factors Surveillance.
AB  - BACKGROUND: Obesity is an important and life-threatening disease, associated with
      different chronic conditions such as cardiovascular disease, diabetes, and
      dyslipidemia. We sought to address the paucity of information on the trends of
      anthropometric indices such as weight, waist circumference, and body mass index
      in the adult population of Iran. METHODS: We drew upon data from the First Non
      communicable Disease Survey in Iran in 2005. In total, 79,611 participants
      between 20 and 64 years old were selected via the random multistage cluster
      sampling. The Lambda Median Scale method was applied to construct normal curves
      for anthropometric indices. RESULTS: The mean of waist circumference in both
      genders increased with age and in all the age groups except those between 20 and
      24 years old was higher in the women. The mean of body mass index was higher in
      all the age brackets in the women, but the means of weight and height were higher
      in the men. The association of theses indices with diabetes, hypertension, and
      dyslipidemia was stronger in men. CONCLUSION: The ranges of waist circumference
      and body mass index in Iranian population are different from those of other
      countries. The higher body mass index and waist circumference in females and the
      direct association between obesity and chronic diseases, is advisable that the
      effects of this phenomenon be fully investigated and due heed be paid to the
      importance of lifestyle modification.

PMID- 23113165
TI  - Community mobilization for youth health promotion: a lesson learned from iran.
AB  - BACKGROUND: More than 36 % of the total population of Iran consists of young
      people aged 15 to 25 yr. Recent studies show that this age group has the highest
      rate of serious health problems. Youth participatory studies on youth health
      priority have shown that mental health is one of the most important priorities in
      youth health. Aim to assessing the mental health needs of youth we conducted a
      peer group based multidisciplinary study. METHODS: To conduct a multi
      disciplinary approach through involving youth for finding their mental health
      needs and their suggestion for solving them, we designed a qualitative approach
      based on grounded theory. To data collection, we used a semi-structured guide
      questionnaire. Sixteen focus group discussions were conducted by trained peers
      with youth aged 15-25 years. RESULT: According to FGDs results, most of youth
      health needs concern with their interpersonal communications skills particularly
      with their parents'; they had some problems with their parental expectations
      meet; life skills; self-expression and problem solving process. They were
      extremely interested in participatory approach in which they involved in
      assessment and determination of their health problems also in designing health
      programs. CONCLUSION: Success of program shows empowering the community through
      capacity building and notice to peer group-based interventions to critical
      enhancing in various aspects of youth health is the most effective method to
      needs assessment and community mobilization for better health.

PMID- 23113164
TI  - Mental health and well-being in different levels of perceived discrimination.
AB  - BACKGROUND: To compare mental health and well-being in different levels of the
      perceived discrimination among Iranian people living in Tehran. METHOD: Using
      multi-stage sampling, 1255 subjects with the average age of 45 years and 9 months
      (including 672 women and 583 men) were selected and they completed all items of
      the general health questionnaire (GHQ), the social well-being inventory (SWI),
      personal well-being inventory (PWI), and a question to assess the perceived
      discrimination. RESULTS: Data analysis by Kruskal-Wallis test revealed that there
      were significant differences between physical symptoms (chi(2)=5.93, P<0.05) and
      depression (chi (2)=15.70, P<0.05), the subscales of mental health in different
      levels of the perceived discrimination. Furthermore, comparing personal well
      being scores and its subscales in different levels of the perceived
      discrimination showed significant differences in personal hygiene (chi(2)=7.20,
      P<0.05), and security in future (chi(2)=7.60, P<0.05). Emotional well-being
      (chi(2)=12.25, P<0.05), self-rule (chi(2)=7.45, P<0.05), personal growth
      (chi(2)=19.87, P<0.05), and psychological well-being (chi(2)= 9.09, P<0.05) were
      significantly different in different levels of the perceived discrimination, too.
      Moreover, comparing social well-being in different levels of the perceived
      discrimination indicated significant differences between social acceptance (chi
      (2)=14.91, P<0.05), and social participation (chi (2)= 10.91, P<0.05).
      CONCLUSION: Therefore, people are more active in society, increases the
      possibility of encountering with discrimination and consequently the perception
      of that.

PMID- 23113166
TI  - Common methods to treat addiction in treatment- rehabilitation centers in tehran.
AB  - BACKGROUND: This study was to determine common methods to treat addiction used by
      patients checked into Outpatient Treatment and Rehabilitation Clinics in Tehran.
      METHODS: The study was conducted in Social Security affiliated outpatient clinics
      including three governmental and several private centers in 22 districts of
      Tehran. Demographic data, personal information, social characteristics and
      information regarding prevention, treatment, and follow-up records of 1,372
      patients were obtained and analyzed. RESULTS: A majority of cases referring to
      the treatment centers were male (95.2%). Patients were 14 to 75 yr (mean 35.48 +/
      10.57 yr); 61.7% were married and lived in rented homes in the city; 938/1372
      (68.4%) had at least one previous attempt failure when seeking re-treatment. A
      majority of them (77.8%) had a history of 1 to 4 quit attempts; a number 63.1%
      had an abstinence period of 1 week to 6 months. CONCLUSION: The majority of our
      understudy subjects had a history of previous attempts to treat their addiction
      with a maximum abstinence period of 6 months.

PMID- 23113167
TI  - Residential segregation and infant mortality: a multilevel study using Iranian
      census data.
AB  - BACKGROUND: There is a great amount of literature concerning the effect of racial
      segregation on health outcomes but few papers have discussed the effect of
      segregation on the basis of social, demographic and economic characteristics on
      health. We estimated the independent effect of segregation of determinants of
      socioeconomic status on infant mortality in Iranian population. METHODS: For
      measuring segregation, we used generalized dissimilarity index for two group and
      multi group nominal variables and ordinal information theory index for ordinal
      variables. Sample data was obtained from Iranian latest national census and
      multilevel modeling with individual variables at level one and segregation
      indices measured at province level for socioeconomic status variables at level
      two were used to assess the effect of segregation on infant mortality. RESULTS:
      Among individual factors, mother activity was a risk factor for infant mortality.
      Segregated provinces in regard to size of the house, ownership of a house and
      motorcycle, number of literate individual in the family and use of natural gas
      for cooking and heating had higher infant mortality. Segregation indices measured
      for education level, migration history, activity, marital status and existence of
      bathroom were negatively associated with infant mortality. CONCLUSION:
      Segregation of different contextual characteristics of neighborhood had different
      effects on health outcomes. Studying segregation of social, economic, and
      demographic factors, especially in communities, which are racially homogenous,
      might reveal new insights into dissimilarities in health.

PMID- 23113168
TI  - The Psychometric Properties of the Farsi Version of "Hospital Survey on Patient
      Safety Culture" In Iran's Hospitals.
AB  - BACKGROUND: If you want to start a long journey towards patient safety, you
      should create a good culture of patient safety among employees alongside
      structural interventions. The first step in doing so is the assessment of current
      culture in the organization using different tools. One of the most commonly used
      instruments of measuring patient safety culture is Hospital Survey of Patient
      Safety culture (HSOPS). The aim of this study was to assess the validity and
      reliability of Farsi version of this questionnaire for the first time in Iran's
      hospitals. METHODS: We purposefully selected four hospitals out of seven general
      Tehran University of Medical Sciences affiliated hospitals. Then a 420 sample of
      staff of these hospitals were taken randomly. Staff was asked to complete the
      questionnaire. Confirmative factor analysis, correlation coefficient, Cronbach's
      alpha were employed in statistical analyses. RESULTS: Factor loadings for almost
      all questions were acceptable. Factors jointly explained 77.8% of the variance in
      the responses. The Cronbach's alpha coefficient was between 0.57 and 0.8. The
      study revealed that over 70% of employees were working at their hospitals more
      than 40 hours a week and also more than half of the employees were not reporting
      errors. CONCLUSION: Farsi version of HSOPS with 12 dimensions and 42 questions is
      a valid and reliable questionnaire to measure patient safety culture for the
      first time in Iran hospitals. This tool will be helpful in tracking improvements
      and in heightening awareness on patient safety culture in Iran.

PMID- 23113169
TI  - Performance evaluation of different filter media in turbidity removal from water
      by application of modified qualitative indices.
AB  - BACKGROUND: Water filtration units have been faced problems in water turbidity
      removal related to their media, which is determined by qualitative indices.
      Moreover, Current qualitative indices such as turbidity and escaping particle
      number could not precisely determine the efficiency of the media in water
      filtration, so defining new indices is essential. In this study, the efficiency
      of Anthracite-Silica and LECA-Silica media in turbidity removal were compared in
      different operating condition by using modified qualitative indices. METHODS: The
      pilot consisted of a filter column (one meter depth) which consisted of a layer
      of LECA (450 mm depth) and a layer of Silica sand (350 mm depth. Turbidities of
      10, 20, and 30 NTU, coagulant concentrations of 4, 8, and 12 ppm and filtration
      rates of 10, 15, and 20 m/h were considered as variables. RESULTS: The LECA
      Silica media is suitable media for water filtration. Averages of turbidity
      removal efficiencies in different condition for the LECA-Silica media were 85.8+/
      5.37 percent in stable phase and 69.75+/-3.37 percent in whole operation phase,
      while the efficiency of total system were 98.31+/-0.63 and 94.49+/-2.97 percent,
      respectively. CONCLUSION: The LECA layer efficiency in turbidity removal was
      independent from filtration rates and due to its low head loss; LECA can be used
      as a proper medium for treatment plants. Results also showed that the particle
      index (PI) was a suitable index as a substitute for turbidity and EPN indices.

PMID- 23113170
TI  - Epidemiological features of visceral leishmaniasis in fars province, southern
      iran.
AB  - BACKGROUND: To describe the epidemiological features of pediatric visceral
      leishmaniasis in southern Iran. METHODS: This retrospective study was carried out
      using local hospital records of VL patients from 2001 through 2009. Data such as
      age, gender, place of residence, clinical signs and symptoms, treatment, history
      of recurrence were recorded. The collected data were statistically analyzed using
      SPSS software. RESULTS: A total of 260 cases of VL have been recorded during 2001
      to 2009 in south of Iran, based on hospital records. Mean age of patients was 3.5
      years with the highest prevalence in 2 years old patients. The diseases have been
      more common in males (60%). The main clinical signs and symptoms of the patients
      were fever (96.2%), hepatosplenomegaly (68.8%) and abdominal protrusion (71.9%).
      Most of cases were from Kazeroun County (17.5%) in Fars Province followed by
      Borazjan in Boushehr Province. Bone marrow aspirations have been performed in 178
      of cases and Leishmania amastigotes were detected in only 50 (28.1%) cases.
      Glucantime has been the first drug treatment while 19.3% of cases have been
      treated with amphotericin B. Mortality rate was 6.2% and children under 1 year
      old have been the main victim of the disease. Relapse has been noted in 7.3% of
      patients. CONCLUSION: VL is still endemic in South of Iran, especially in Fars
      Province with a noticeable mortality rate. Moreover, cases of the diseases are
      reporting from neighboring provinces and this might be due to the spreading of
      the diseases to the adjacent provinces.

PMID- 23113171
TI  - Applying Activity Based Costing (ABC) Method to Calculate Cost Price in Hospital
      and Remedy Services.
AB  - BACKGROUND: Activity Based Costing (ABC) is one of the new methods began
      appearing as a costing methodology in the 1990's. It calculates cost price by
      determining the usage of resources. In this study, ABC method was used for
      calculating cost price of remedial services in hospitals. METHODS: To apply ABC
      method, Shahid Faghihi Hospital was selected. First, hospital units were divided
      into three main departments: administrative, diagnostic, and hospitalized.
      Second, activity centers were defined by the activity analysis method. Third,
      costs of administrative activity centers were allocated into diagnostic and
      operational departments based on the cost driver. Finally, with regard to the
      usage of cost objectives from services of activity centers, the cost price of
      medical services was calculated. RESULTS: The cost price from ABC method
      significantly differs from tariff method. In addition, high amount of indirect
      costs in the hospital indicates that capacities of resources are not used
      properly. CONCLUSION: Cost price of remedial services with tariff method is not
      properly calculated when compared with ABC method. ABC calculates cost price by
      applying suitable mechanisms but tariff method is based on the fixed price. In
      addition, ABC represents useful information about the amount and combination of
      cost price services.

PMID- 23113172
TI  - Molecular Characterization of Environmental Non-Tuberculous Mycobacteria Using
      PCR- RFLP Analysis of 441 Bp Heat Shock Protein 65 Fragments.
AB  - BACKGROUND: Non- Tuberculous Mycobacteria are environmental opportunistic
      pathogens that can be found in various terrestrial and aquatic habitats. There
      are an epidemiological links between species isolated in tap water and those
      isolated from patients. hsp65 gene has more variability in its sequences,
      compared to the some more conserved genes in NTM, for identification of
      mycobacteria to species level. In this study, the prevalence of NTM in Isfahan
      City water samples was determined using culture, biochemical tests and PCR-RFLP
      analyses of hsp65 gene. METHODS: Eighty-five water samples were collected and
      cultured. The mycobacterial isolates were identified by conventional biochemical
      tests. A 441 bp fragment of hsp65 genes was amplified and digested by two
      restriction enzymes, BstEII and HaeII. Digested products were analyzed using
      polyacrilamid gel electrophoresis (PAGE). RESULTS: 25.9% of the water samples
      contained different species of NTM. Dominant isolates were M. fortuitum (26.7%),
      M. chelonae like organism (13.3%) and M. mucogenicum (13.3%). Nineteen isolates
      of Mycobacteria were differentiated using hsp65 genes PCR-RFLP. Three isolates
      could not be identified at the species level because their RFLP patterns were
      different from other known PCR-RFLP profiles. There were different hsp65 gene PCR
      RFLP profiles produced by digestion with BstEII and HaeIII. CONCLUSION: This
      study showed that PCR-RFLP of hsp65 gene in mycobacteria is more reliable method
      for identification of NTM at the specie level than conventional phenotypic
      methods (P<0.05). In comparing of RFLP patterns of this study to other
      investigation, some minor differences were negligible.

PMID- 23113173
TI  - The effects of atmospheric processes on tehran smog forming.
AB  - Air pollution is one of the most important problems in urban areas that always
      threaten citizen's health. Photochemical smog is one of the main factors of air
      pollution in large cities like Tehran. Usually smog is not only a part of nature,
      but is being analyzed as an independent matter, which highly affects on the
      nature. It has been used as relationship between atmospheric elements such as
      temperature, pressure, relative humidity, wind speed with inversion in the time
      of smog forming and weather map in 500 Hpa level during 9 years descriptive
      static by using correlation coefficient in this analyze. Results show that there
      is a meaningful correlation between atmospheric elements and smog forming. This
      relation is seen between monthly average of these elements and monthly average of
      smog forming. However, when temperature decreases, corresponding pressure will
      increase and result of this will be smog forming. Usually smog increases in cold
      months of year due to enter cold high pressure air masses in Iran during December
      and January that is simultaneous with decreasing temperature and air pressure
      increases and inversion height distance decreases from the earth surface which
      cause to integrate air pollution under its surface, will cause to form smog in
      Tehran. It shows a meaningful and strong relation, based on resultant relations
      by correlation coefficient from inversion height and smog forming, so that
      obtained figure is more than 60% .

PMID- 23113174
TI  - Genomics and public health research: can the state allow access to genomic
      databases?
AB  - Because many diseases are multifactorial disorders, the scientific progress in
      genomics and genetics should be taken into consideration in public health
      research. In this context, genomic databases will constitute an important source
      of information. Consequently, it is important to identify and characterize the
      State's role and authority on matters related to public health, in order to
      verify whether it has access to such databases while engaging in public health
      genomic research. We first consider the evolution of the concept of public
      health, as well as its core functions, using a comparative approach (e.g. WHO,
      PAHO, CDC and the Canadian province of Quebec). Following an analysis of relevant
      Quebec legislation, the precautionary principle is examined as a possible avenue
      to justify State access to and use of genomic databases for research purposes.
      Finally, we consider the Influenza pandemic plans developed by WHO, Canada, and
      Quebec, as examples of key tools framing public health decision-making process.
      We observed that State powers in public health, are not, in Quebec, well adapted
      to the expansion of genomics research. We propose that the scope of the concept
      of research in public health should be clear and include the following
      characteristics: a commitment to the health and well-being of the population and
      to their determinants; the inclusion of both applied research and basic research;
      and, an appropriate model of governance (authorization, follow-up, consent,
      etc.). We also suggest that the strategic approach version of the precautionary
      principle could guide collective choices in these matters.

PMID- 23113175
TI  - Air pollution, its mortality risk, and economic impacts in tehran, iran.
AB  - BACKGROUND: Air pollution in Tehran is widely recognized as a serious
      environmental challenge, posing significant threats to the health of the resident
      population. Improving air quality will be difficult for many reasons, including
      climate and topography, heavy dependence on motor vehicles for mobility, and
      limited resources to reduce polluting emissions. Consequently, it is useful to
      have information regarding the scale of the health threat and the economic value
      of reducing that threat. METHODS: This paper integrates information on air
      quality, population, economic valuation, and health science to assess the most
      serious impact of fine particle pollution on humans, which is increased mortality
      risk, and provides estimates of the costs of present pollution levels, both in
      terms of risk and in terms of economic value relative to attaining air quality
      standards. RESULTS: Mid-range results indicate that mortality risk for the
      population aged 30 and over would be reduced from 8.2 per 1,000 residents
      annually to 7.4 per 1,000 and that the estimated annual economic benefits of this
      reduced risk would be $378.5 million, if health-based World Health Organization
      recommended annual average PM(2.5) standards were met. CONCLUSIONS: The potential
      public health benefits of reducing particulate air pollution are significant, and
      will increase with growing population.

PMID- 23113176
TI  - Is suicide predictable?
AB  - BACKGROUND: THE CURRENT STUDY AIMED TO TEST THE HYPOTHESIS: Is suicide
      predictable? And try to classify the predictive factors in multiple suicide
      attempts. METHODS: A cross-sectional study was administered to 223 multiple
      attempters, women who came to a medical poison centre after a suicide attempt.
      The participants were young, poor, and single. A Logistic Regression Analiysis
      was used to classify the predictive factors of suicide. RESULTS: Women who had
      multiple suicide attempts exhibited a significant tendency to attempt suicide
      again. They had a history for more than two years of multiple suicide attempts,
      from three to as many as 18 times, plus mental illnesses such as depression and
      substance abuse. They also had a positive history of mental illnesses.
      CONCLUSION: Results indicate that contributing factors for another suicide
      attempt include previous suicide attempts, mental illness (depression), or a
      positive history of mental illnesses in the family affecting them at a young age,
      and substance abuse.

PMID- 23113177
TI  - Modeling the Underlying Predicting Factors of Tobacco Smoking among Adolescents.
AB  - BACKGROUND: With regard to the willing and starting tobacco smoking among young
      people in Iran. The aim of the study was to model the underlying factors in
      predicting the behavior of tobacco smoking among employed youth and students in
      Iran. METHODS: In this analytical cross-sectional study, based on a random
      cluster sampling were recruited 850 high school students, employed and unemployed
      youth age ranged between 14 and 19 yr from Iran. The data of demographic and
      tobacco smoking related variables were acquired via a self-administered
      questionnaire. A series of univariate and multivariate logistic regressions were
      performed respectively for computing un-adjusted and adjusted Odds Ratios
      utilizing SPSS 17 software. RESULTS: A number of 189 persons (25.6%) were smoker
      in the study and the mean smoking initiation age was 13.93 (SD= 2.21). In
      addition, smoker friend, peer persistence, leaving home, and smoking in one and
      six month ago were obtained as independent predictors of tobacco smoking.
      CONCLUSIONS: The education programs on resistance skills against the persistence
      of the peers, improvement in health programs by governmental interference and
      policy should be implemented.

PMID- 23113178
TI  - Classification of health structural indicators using scalogram model in golestan
      province, northern iran.
AB  - BACKGROUND: One of the main and basic pillars of health system promotion is the
      equitable distribution of health facilities in order to ensure fair access of
      people in the community to the health services. The goal of this study was to
      classify the health structural indicators in Golestan Province using Scalogram
      analysis model. METHOD: A descriptive study was conducted in 2010. Data related
      to indicators in 3 categories of institutional, human resources and rural health
      and their indicators were collected using statistical yearbook. Data analysis was
      done using SPSS software and scalogram analysis model. RESULTS: There is large
      gap between health structural indicators in cities of Golestan Province. Aq Qala
      City with 97 score and Azad Shahr City with 41 score were the most and lowest
      scores respectively from enjoyment of health structural indicators. Generally,
      18% of cities were in less developed level and only 27% of cities were developed
      level. CONCLUSION: To achieve a fair and balanced healthcare status in different
      provinces based on their state of development, plans should be arranged in order
      to reduce the gap in the access to healthcare facilities.

PMID- 23113179
TI  - The Assessment of Relations between Socioeconomic Status and Number of
      Complications among Type 2 Diabetic Patients.
AB  - BACKGROUND: The prevalence of diabetes mellitus among Iranian aged 25-64
      estimated to be about 7.7%. The aim of current study was the assessment of
      socioeconomic status of diabetic patients and their complications. METHODS: A
      cross sectional study was conducted on type 2 diabetic patients with
      complications in four major teaching hospitals affiliated to Tehran University of
      Medical Sciences (TUMS) during July 2009 to March 2010. All patients (530) were
      interviewed through a questionnaire with 85% response rate (450 patients).
      Skilled nurses were assigned as responsible for data collection. Collected data
      analyzed by Exact Fisher and chi2 tests using SPSS version 11.5. RESULTS: The
      majority of patients had experienced one or more complications. Findings revealed
      that 50%, 33.6% and 16.4% of the patients suffered from one, two, and three
      complications of type 2 diabetes, respectively. Patients with cardiovascular
      complications included 22.2%, with both cardiovascular and eye complications
      (12.7%), and with cardiovascular, eye and foot ulcer together 14% of the
      respondents. Frequency of complications demonstrated significant relation with
      sex, age, educational level, type of occupation, duration of diabetes (P<0.001)
      and social class (P=0.002). The majority of patients (54.2%) belonged to low
      income group. CONCLUSION: It seems patients with low socioeconomic status face
      more challenges in their social environment together with less psychological
      support. Health care systems are responsible to empower them to control their
      illness and feel a better life to live.

PMID- 23113181
TI  - Organizational citizenship behavior among Iranian nurses.
AB  - BACKGROUND: Organizational Citizenship Behavior (OCB) is defined as "individual
      behavior that is discretionary, not directly or explicitly recognized by the
      formal reward system, and that in the aggregate, promotes the effective
      functioning of organization". OCB, enhance job satisfaction among nursing
      employees. According to several findings, nurses' OCB have a positive and
      significant influence on job satisfaction. This research is aimed to study OCB
      among Iranian nurses. METHODS: A cross-sectional, descriptive and analytical
      study was conducted among 510 nurses working in 15 teaching hospitals in Tehran,
      Iran to be selected by stratified random sampling. The respondents were asked to
      complete Netemeyer's organizational citizenship behavior questionnaire that
      encompassed four dimensions of OCB including Sportsmanship, Civil Virtue,
      Conscientiousness, Altruism and selected each item of OCB dimensions and
      identified their attitudes about OCB items were observed in hospitals of Tehran.
      The data was analyzed by T-test, ANOVA and Pearson statistical methods. RESULTS:
      The results of this research showed that most of the nurses who studied in this
      study, had OCB behaviors. Also, we found that there was significant correlation
      between Iranian nurses' marriage status, qualifications and gender with
      sportsmanship, altruism and civic virtue. CONCLUSION: This research demonstrates
      the existence of OCB among Iranian nurses that are essential in developing
      patient - oriented behavior. The results can be used to develop further nursing
      management strategies for enhancement of OCB. Finally, the present study
      indicates new possibilities for future researches such as analysis and comparison
      of OCB between different hospitals and how nursing policy-makers can enhance
      these behaviors in Iranian hospitals.

PMID- 23113180
TI  - Recombinant outer capsid glycoprotein (VP7) of rotavirus expressed in insect
      cells induces neutralizing antibodies in rabbits.
AB  - BACKGROUND: Rotaviruses cause diarrhea in infants and young children worldwide.
      Rotavirus outer capsid protein, VP7 is major neutralizing antigen that is
      important component of subunit vaccine to prevent rotavirus infection. Many
      efforts have been done to produce recombinant VP7 that maintain native
      characteristics. We used baculovirus expression system to produce rotavirus VP7
      protein and to study its immunogenicity. METHODS: Simian rotavirus SA11 full
      length VP7 ORF was cloned into a cloning plasmid and then the cloned gene was
      inserted into the linear DNA of baculovirus Autographa californica Nuclear
      Polyhedrosis Virus (AcNPV) downstream of the polyhedrin promoter by in vitro
      recombination reactions. The expressed VP7 in the insect cells was recognized by
      rabbit hyperimmune serum raised against SA11 rotavirus by Immunofluorescence and
      western blotting assays. Rabbits were immunized subcutaneously by cell extracts
      expressing VP7 protein. RESULTS: Reactivity with anti-rotavirus antibody
      suggested that expressed VP7 protein had native antigenic determinants. Injection
      of recombinant VP7 in rabbits elicited the production of serum antibodies, which
      were able to recognize VP7 protein from SA11 rotavirus by Western blotting test
      and neutralized SA11 rotavirus in cell culture. CONCLUSION: Recombinant outer
      capsid glycoprotein (VP7) of rotavirus expressed in insect cells induces
      neutralizing antibodies in rabbits and may be a candidate of rotavirus vaccine.

PMID- 23113182
TI  - Estimating the contribution of selected risk factors in attributable burden to
      stroke in iran.
AB  - BACKGROUND: Knowledge of the magnitude of avoidable burden by risk factors is
      needed for health policy, priority setting, and preventing stroke. The aim of
      this study was to estimate the contribution of selected risk factors including
      hypertension, overweight, obesity, tobacco use, and physical inactivity to the
      attributable burden of stroke in Iran. METHODS: The World Health Organization
      Comparative Risk Assessment (CRA) methodology was employed to calculate the
      Potential Impact Fraction (PIF) and percentage of avoidable burden of stroke,
      which attributed to its risk factors among Iranian adults in 2009. Prevalence of
      risk factors was obtained from the 5(th) STEPS survey of chronic disease risk
      factors which conducted in 2009. PIF was estimated on both theoretical minimum
      and feasible minimum risk. A simulation procedure incorporating sources of
      uncertainty was used to estimate the uncertainties for the attributable burden.
      RESULTS: About 15.7% (95% uncertainty intervals: 5.8- 23.5) of attributable
      Disability Adjusted Life Years (DALYs) to stroke in adult males and 15.8% (95%
      uncertainty intervals: 5.8- 23.5) in adult females are avoidable after changing
      the current prevalence (16.0% and 16.1% for males and females, respectively) of
      hypertension to 10% in both sexes. CONCLUSION: This work highlighted the
      important role of hypertension and overweight. Accordingly, policy makers are
      advised to consider these risk factors once implementing interventional program
      in Iran.

PMID- 23113183
TI  - Genetic Diversity and Balancing Selection within the Human Phenylalanine
      Hydroxylase (PAH) Gene Region in Iranian Population.
AB  - BACKGROUND: Genetic diversity of three polymorphic markers in the phenylalanine
      hydroxylase (PAH) gene region including PvuII (a), PAHSTR and MspI were
      investigated. METHODS: Unrelated individuals (n=139) from the Iranian populations
      were genotyped using primers specific to PAH gene markers including PvuII(a),
      MspI and PAHSTR. The amplified products for PvuII(a), MspI were digested using
      the appropriate restriction enzymes and separated on 1.5% agarose. The PAHSTR
      alleles were identified using polyacrylamide gel electrophoresis followed by
      silver staining. The exact size of the STR alleles was determined by sequencing.
      The allele frequency and population status of the alleles were estimated using
      PHASE, FBAT and GENEPOP software. RESULTS: The estimated degree of heterozygosity
      for PAHSTR, MspI and PvuII (a) was 66%, 56% and 58%, respectively. The haplotype
      estimation analysis of the markers resulted in nine informative haplotypes with
      frequencies >=5%. Moreover, the results obtained from Ewens-Watterson test for
      neutrality suggested that the markers were under balancing selection in the
      Iranian population. CONCLUSION: These findings suggested the presence of genetic
      diversity at these three markers in the PAH gene region. Therefore, the markers
      could be considered as functional markers for linkage analysis of the PAH gene
      mutations in the Iranian families with the PKU disease.

PMID- 23113184
TI  - Serum selenium, zinc, and copper in early diagnosed patients with pemphigus
      vulgaris.
AB  - BACKGROUND: Pemphigus vulgaris is a life threatening, blistering skin disease. It
      is an autoimmune abnormality. Due to involvement of oral cavity and pharynx,
      patients are at risk of nutrients deficiency. The aim of this study was to
      evaluate the status of selenium, copper, and zinc in these patients. METHODS: In
      a case-control study, 43 newly diagnosed pemphigus vulgaris patients were
      compared with 58 healthy people from 2009 to 2010. The severity of the disease
      was estimated according to Harman's scores. Serum selenium was measured with
      atomic absorption but serum zinc and copper concentrations were determined
      spectrophotometrically. Data were compared with independent t test. Correlations
      were evaluated by Pearson correlation test. RESULTS: Both groups were the same
      based on sex, age, and weight and body mass index. The mean duration of disease
      was 5.6 month. The oral and skin severities were 1.79 and 2.3 respectively, based
      on Harman's scores. Serum selenium of pemphigus patients was significantly less
      than that of healthy people (P<0.001). Serum copper was negatively correlated
      with duration of disease in males (P=0.02, r=-0.5). CONCLUSIONS: Pemphigus
      vulgaris negatively affects on serum selenium, copper and zinc. It seems that
      serum selenium, copper and zinc decrease as the disease lasts longer.

PMID- 23113185
TI  - Assessment of Internal Validity of Prognostic Models through Bootstrapping and
      Multiple Imputation of Missing Data.
AB  - BACKGROUND: Prognostic models have clinical appeal to aid therapeutic decision
      making. Two main practical challenges in development of such models are
      assessment of validity of models and imputation of missing data. In this study,
      importance of imputation of missing data and application of bootstrap technique
      in development, simplification, and assessment of internal validity of a
      prognostic model is highlighted. METHODS: Overall, 310 breast cancer patients
      were recruited. Missing data were imputed 10 times. Then to deal with sensitivity
      of the model due to small changes in the data (internal validity), 100 bootstrap
      samples were drawn from each of 10 imputed data sets leading to 1000 samples. A
      Cox regression model was fitted to each of 1000 samples. Only variables retained
      in more than 50% of samples were used in development of final model. RESULTS:
      Four variables retained significant in more than 50% (i.e. 500 samples) of
      bootstrap samples; tumour size (91%), tumour grade (64%), history of benign
      breast disease (77%), and age at diagnosis (59%). Tumour size was the strongest
      predictor with inclusion frequency exceeding 90%. Number of deliveries was
      correlated with age at diagnosis (r=0.35, P<0.001). These two variables together
      retained significant in more than 90% of samples. CONCLUSION: We addressed two
      important methodological issues using a cohort of breast cancer patients. The
      algorithm combines multiple imputation of missing data and bootstrapping and has
      the potential to be applied in all kind of regression modelling exercises so as
      to address internal validity of models.

PMID- 23113186
TI  - Psychosocial disabilities in patients with schizophrenia.
AB  - BACKGROUND: This study aimed at revaluating the psychosocial disabilities in
      schizophrenic patients. METHODS: In an analytic-descriptive setting,
      schizophrenic patients were evaluated in Razi University Hospital during a one
      year period (2009-10). The study group consisted of male and female patients aged
      18-65 years, with the onset of disease for a minimum of 2 years and at least one
      psychological hospitalization in their medical record. The demographic data, as
      well as the results of the SANS, SAPS, GARF and SOFAS questionnaires were
      determined in each patient. RESULTS: Two hundred and eight patients, 53 females,
      and 155 males with the mean age of 36.96+/-11.55 (18-65) years were enrolled.
      Vocational, educational, social, familial, and self-hygiene related disabilities
      were seen in 63.5%, 21.2%, 93.8%, 13.9%, and 48.1% of the patients, respectively.
      Totally, psychosocial disabilities were reported in 98.1% of these patients. The
      mean age of the patients with educational or social disabilities was lower.
      Vocational problems were more common in male patients. Familial and social
      disabilities were positively related to the severity of positive and negative
      symptoms, with the predominance of the latter. Positive and negative symptoms
      were more frequent in patients with social and self-care related disabilities,
      respectively. The duration of the disease was significantly correlated with the
      positive symptoms and familial-social disabilities. CONCLUSION: The current study
      described the high prevalence of psychosocial disabilities in patients with
      schizophrenia and may have implications for public health interventions.

PMID- 23113187
TI  - Transformation of health care in mainland china: hospital violator.

PMID- 23113188
TI  - Central-provincial relations for anti-schistosomiasis policy in china.
AB  - This paper discusses central-local relations for healthcare policy in China from
      a principal-agent perspective, based on schistosomiasis control. In order to
      control the disease, the central government produced the Outline of the Mid-Long
      Term National Plan for Schistosomiasis Prevention and Control (2004-2015) in
      2004. By discussing the implementation of the National Outline at the provincial
      level, the author uses principal-agent theory to examine conflict and
      coordination between the central and provincial governments. The documents were
      collected from the Internet. Although the central and provincial governments all
      want to eliminate schistosomiasis, allocating funding among them creates conflict
      and forms an obstacle to achieving the goal. This paper extensively discusses the
      topics related to central-provincial relation and schistosomiasis control
      program. Further case study on a single province may be needed to intensify the
      discussion from a micro perspective. The conflict between central and provincial
      relations needs to be resolved in order to implement the national policy.

PMID- 23113189
TI  - Crisis management of tohoku; Japan earthquake and tsunami, 11 march 2011.
AB  - The huge earthquake in 11 March 2012 which followed by a destructive tsunami in
      Japan was largest recorded earthquake in the history. Japan is pioneer in
      disaster management, especially earthquakes. How this developed country faced
      this disaster, which had significant worldwide effects? The humanitarian behavior
      of the Japanese people amazingly wondered the word's media, meanwhile the
      management of government and authorities showed some deficiencies. The impact of
      the disaster is followed up after the event and the different impacts are tried
      to be analyzed in different sectors. The situation one year after Japan 2011
      earthquake and Tsunami is overviewed. The reason of Japanese plans failure was
      the scale of tsunami, having higher waves than what was assumed, especially in
      the design of the Nuclear Power Plant. Japanese authorities considered economic
      benefits more than safety and moral factors exacerbate the situation. Major
      lessons to be learnt are 1) the effectiveness of disaster management should be
      restudied in all hazardous countries; 2) the importance of the high-Tech early
      warning systems in reducing risk; 3) Reconsidering of extreme values
      expected/possible hazard and risk levels is necessary; 4) Morality and might be
      taken as an important factor in disaster management; 5) Sustainable development
      should be taken as the basis for reconstruction after disaster.

PMID- 23113190
TI  - Information technologies in public health management: a database on biocides to
      improve quality of life.
AB  - BACKGROUND: Biocides for prolonging the shelf life of a large variety of
      materials have been extensively used over the last decades. It has estimated that
      the worldwide biocide consumption to be about 12.4 billion dollars in 2011, and
      is expected to increase in 2012. As biocides are substances we get in contact
      with in our everyday lives, access to this type of information is of paramount
      importance in order to ensure an appropriate living environment. Consequently, a
      database where information may be quickly processed, sorted, and easily accessed,
      according to different search criteria, is the most desirable solution. The main
      aim of this work was to design and implement a relational database with complete
      information about biocides used in public health management to improve the
      quality of life. METHODS: Design and implementation of a relational database for
      biocides, by using the software "phpMyAdmin". RESULTS: A database, which allows
      for an efficient collection, storage, and management of information including
      chemical properties and applications of a large quantity of biocides, as well as
      its adequate dissemination into the public health environment. CONCLUSION: The
      information contained in the database herein presented promotes an adequate use
      of biocides, by means of information technologies, which in consequence may help
      achieve important improvement in our quality of life.

PMID- 23113191
TI  - Role of NGOs and CBOs in Waste Management.
AB  - BACKGROUND: Developing cities like Khulna, the third largest metropolitan city in
      Bangladesh, have now begun to confess the environmental and public health risks
      associated with uncontrolled dumping of solid wastes mainly due to the active
      participation of non-governmental organizations (NGOs) and community-based
      organizations (CBOs) in municipal solid waste (MSW) management. METHODS: A survey
      was conducted to observe the present scenarios of secondary disposal site (SDS),
      ultimate disposal site (UDS), composting plants, medical wastes management and
      NGOs and CBOs MSW management activities. RESULTS: A total of 22 NGOs and CBOs are
      involved in MSW management in 31 wards of Khulna City Corporation. About 9 to 12%
      of total generated wastes are collected by door-to-door collection system
      provided by mainly NGOs and CBOs using 71 non-motorized rickshaw vans. A major
      portion of collected wastes is disposed to the nearest SDS by these organizations
      and then transferred to UDS or to private low-lying lands from there by the city
      authority. A small portion of organic wastes is going to the composting plants of
      NGOs. CONCLUSION: The participation of NGOs and CBOs has improved the overall MSW
      management system, especially waste collection process from sources and able to
      motivate the residents to store the waste properly and to keep clean the
      premises.

PMID- 23113192
TI  - Water-borne diseases, cost of illness and willingness to pay for diseases
      interventions in rural communities of developing countries.
AB  - BACKGROUND: Almost one third of the global population is living in developing
      South Asia where disease occurrence is high especially in rural areas and people
      are unaware of water-borne diseases and cost of illness. METHODS: The
      quantitative approach involved questionnaire based study (n=50 households). The
      community awareness, the occurrence of water-borne diseases with related cost of
      illness and community participation for the introduction of health interventions
      for water-borne diseases were evaluated through cross-tabulations, correlations,
      and ANOVA. RESULTS: Majority (40%) of the community had no knowledge of water
      borne diseases except some had little knowledge of diarrhea and typhoid. Diarrhea
      followed by stomach diseases was widespread in the community. Population below
      poverty level was bearing the cost of illness around US$ 0.6-1.2 (Rs 50-100) per
      day followed by low and average income level with direct cost of US$ 2.3 (Rs 200)
      per day. The indirect cost of illness had showed increasing trend between US$ 2.3
      4.7 (Rs 200-400) per day with increase in income levels. Maximum willingness to
      pay (WTP) for water supply and sewerage system was US$ 3.6 (Rs 300) and US$ 1.2
      (Rs 100) per month respectively. Income and water supply demand was strongly
      correlated with acceptability to pay for the facilities (r = 0.319, 0.307; P<
      0.05). Income had a strong influence on WTP for water and sewerage system (r =
      0.805, 0.797; P< 0.05). CONCLUSION: To maintain rural health, water-borne
      diseases can be reduced by introducing health interventions like proper water and
      sanitation facilities.

PMID- 23113193
TI  - Association between Frequency of Breakfast Eating and Obesity in Korean
      Adolescents.
AB  - BACKGROUND: The purpose of this study was to examine whether the frequency of
      breakfast eating was related with overweight/obesity in Korean adolescents.
      METHOD: We analyzed the data collected in the 5(th) KYRBWS, in which 72,399
      adolescents participated in 2009. We assessed the association between frequency
      of breakfast eating and body mass index by using multivariate logistic regression
      analysis. RESULTS: A total of 20,962(54.9%) boys and 18,479(54.0%) girls skipped
      breakfast 7 days(all days) per week at baseline. For boys, the odds ratios(ORs)
      between being overweight and frequency of breakfast eating were 1.040 for 3-5
      times per week, 1.092 for 1-2 time(s) per week, 1.059 for no breakfast per week,
      compared to 6-7 times per week(p>0.05). The ORs between being obese and frequency
      of breakfast eating were 1.011 for 3-5 times per week, 0.968 for 1-2 time(s) per
      week, and 0.932 for no breakfast per week, compared to 6-7 times per
      week(p>0.05). For girls, the ORs between being overweight and frequency of
      breakfast eating were 0.990 for 3-5 times per week, 0.992 for 1-2 time(s) per
      week, 1.019 for no breakfast per week, compared to 6-7 times per week(p>0.05).
      The ORs between being obese and frequency of breakfast eating were 1.075 for 3-5
      times per week, 0.946 for 1-2 time(s) per week, and 0.941 for no breakfast per
      week, compared to 6-7 times per week(p>0.05). CONCLUSION: The frequency of
      breakfast eating has no correlation with overweight/obesity in Korean
      adolescents.

PMID- 23113194
TI  - Classification of Death Rate due to Women's Cancers in Different Countries.
AB  - BACKGROUND: The two most frequently diagnosed cancers among women worldwide are
      breast and cervical cancers. The objective of the present study was to classify
      the different countries based on the death rates from sex specific cancers.
      METHODS: In this cross-sectional study, we used dataset regarding death rate from
      breast, cervical, uterine, and ovarian cancers in 190 countries worldwide
      reported by World Health Organization. Normal mixture models were fitted with
      different numbers of components to these data. The model's parameters estimated
      using the EM algorithm. Then, appropriate number of components was determined and
      was selected the best-fit model using the BIC criteria. Next, model-based
      clustering was used to allocate the world countries into different clusters based
      on the distribution of women's cancers. The MIXMOD program using MATLAB software
      was used for data analysis. RESULTS: The best model selected with four
      components. Then, countries were allocated into four clusters including 43 (23%)
      in the first cluster, 28 (14%) in the second cluster, 75 (39%) in the third
      cluster, and 44 (24%) in the fourth cluster. Most countries in South America were
      to the first cluster. In addition, most countries in Africa, Central, and
      Southeast Asia were located to the third cluster. Furthermore, the fourth cluster
      consisted of Pacific continent, North America and European countries. CONCLUSION:
      Considering the benefits of clustering based on normal mixture models, it seems
      that can be applied this method in wide variety of medical and public heath
      contexts.

PMID- 23113195
TI  - Inhibition of Leishmania major PTR1 Gene Expression by Antisense in Escherichia
      coli.
AB  - BACKGROUND: Protozoa related to Trypanosome family including Leishmania,
      synthesize enzymes to escape from drug therapy. One of them is PTR1 that its
      enzymatic activity is similar to dihydrofolate reductase (DHFR). Dihydrofolate
      reductase - thymidylate synthase has a major role in DNA synthesis, if it is
      inhibited, the result would be the death of parasite. Since PTR1 activity is
      similar to DHFR, causes the decrease of inhibition effect of drug. The aim of
      this study was inhibition of Iranian L. major PTR1 expression with mRNA antisense
      in prokaryotic system as an approach to appear of the drugs therapeutic effects
      more. METHODS: PTR1 gene was ligated to pACYCDuet-1 and pcDNA3 plasmids as sense
      and antisense plasmids, respectively. Simultaneously transfer of sense and
      antisense plasmids was done in E. coli strain M15. SDS-PAGE and western blot
      analysis were carried out to analyze the expression. RESULTS: Sense and antisense
      plasmids were prepared and confirmed by restriction analysis and PCR then
      simultaneously transfer of them was done. SDS-PAGE and western blot analysis
      showed PTR1 gene was inhibited by mRNA antisense in bacterial cells. CONCLUSION:
      Expression of PTR1 gene in sense plasmid was inhibited successfully by antisense
      plasmid.

PMID- 23113196
TI  - Effect of Curcumin on Aspergillus parasiticus Growth and Expression of Major
      Genes Involved in the Early and Late Stages of Aflatoxin Biosynthesis.
AB  - BACKGROUND: The effect of curcumin as a natural safe compound with different
      biological activities was examined on fungal growth and aflatoxin production in
      Aspergillus parasiticus NRRL 2999. METHODS: The fungus was cultured in presence
      of serial two-fold concentrations of curcumin (125-2000 MUg/ml) in yeast extract
      sucrose broth for 3 days at 28 degrees C. Mycelia dry weight was determined as an
      index of fungal growth, while aflatoxin production was assessed by high
      performance liquid chromatography (HPLC). The expression of ver-1, nor-1, pksA,
      omtA and aflR genes in aflatoxin biosynthetic pathway was evaluated by real time
      PCR. RESULTS: Curcumin strongly inhibited aflatoxin B(1) production in the range
      of 26.6 to 94.9% by serial two-fold concentrations from 125 to 2000 MUg/ml.
      Fungal growth was also inhibited by the compound in the range of 34.0 to 60.8%.
      Analysis of the expression of aflatoxin pathway genes by real time PCR showed
      that curcumin inhibited the expression of ver-1, nor-1, pksA, omtA and aflR genes
      at concentrations of 250 and 1000 MUg/ml. In concentration of 1000 MUg/ml, gene
      expression was reduced by 31.3%, 44.6%, 57.1% 110.9% and 286.7% accordingly.
      Reduction in the expression of aflatoxin biosynthesis genes was significant only
      for aflR. In ferric reducing ability of plasma (FRAP) assay, curcumin showed
      strong antioxidant activity at all concentrations tested. CONCLUSION: Curcumin
      may be employed successfully as a good candidate in controlling of toxigenic
      fungal growth on food and feed and subsequent contamination with aflatoxins in
      practice.

PMID- 23113197
TI  - The Presentation of Proper Indicators for Evaluation of WHO Collaboration
      Centres' Activities in Iran.
AB  - BACKGROUND: There are thirteen WHO collaborating centres in Iran which no
      mechanism or model has ever been foreseen for the evaluation of them. This
      original research is innovative in Iran, which has been offered by the researcher
      through a joint research project with WHO. METHODS: The aforesaid model has been
      approved by the International Relation Department of Ministry of Health&
      education. This was done to develop model and indicators for evaluation of
      WHOCC's activities in Iran, which includes online survey, reports, literature
      reviews and website searches, published literature in another country, documents
      in Undersecretary for Research and Technology of Iranian Ministry of Health and
      Medical Education. RESULTS: We studied collaboration centres in other countries
      and then compared these indicators together and presented a proper indicators for
      evaluation of WHOCC' activities in Iran. CONCLUSION: Evaluation of WHOCC's
      activities could be used as a mean for implementing policies and promoting
      knowledge production. Evaluation of WHOCC' activities is country's requirements.

PMID- 23113198
TI  - Comparison of logistic regression and artificial neural network in low back pain
      prediction: second national health survey.
AB  - BACKGROUND: The purpose of this investigation was to compare empirically
      predictive ability of an artificial neural network with a logistic regression in
      prediction of low back pain. METHODS: Data from the second national health survey
      were considered in this investigation. This data includes the information of low
      back pain and its associated risk factors among Iranian people aged 15 years and
      older. Artificial neural network and logistic regression models were developed
      using a set of 17294 data and they were validated in a test set of 17295 data.
      Hosmer and Lemeshow recommendation for model selection was used in fitting the
      logistic regression. A three-layer perceptron with 9 inputs, 3 hidden and 1
      output neurons was employed. The efficiency of two models was compared by
      receiver operating characteristic analysis, root mean square and -2 Loglikelihood
      criteria. RESULTS: The area under the ROC curve (SE), root mean square and 
      2Loglikelihood of the logistic regression was 0.752 (0.004), 0.3832 and 14769.2,
      respectively. The area under the ROC curve (SE), root mean square and 
      2Loglikelihood of the artificial neural network was 0.754 (0.004), 0.3770 and
      14757.6, respectively. CONCLUSIONS: Based on these three criteria, artificial
      neural network would give better performance than logistic regression. Although,
      the difference is statistically significant, it does not seem to be clinically
      significant.

PMID- 23113199
TI  - In Vitro Effect of Antigenic Extract of Trichophyton verrucosum on Fibroblast
      Proliferation and Matrix Metalloproteinase -2 Activities.
AB  - BACKGROUND: Trichophyton verrucosum is a zoophilic fungus with a worldwide
      distribution. Our aim was to investigate the proliferative effect of antigenic
      compounds of T. verrucosum on dermis fibro blasts and endothelial cells. METHODS:
      T. verrucosum was cultured in SCC medium and was then transferred to a broth
      medium. Surface antigens of this fungus were separated using the freeze and thaw
      method. The sample was centrifuged and the supernatant was taken. The supernatant
      was homogenized and purified. The prepared antigenic extract was added to fibro
      blast cell lines according to a regular timetable. Cytotoxicity and cell
      proliferation were evaluated using zymography and densitometry in order to assay
      MMPs activity. RESULTS: Statistical analyses showed that this antigenic extract
      is able to enhance the MMPs activity CONCLUSION: Trichophyton verrucosum
      increases the proliferation of dermis germinal layer and MMP-2 activity, which
      has a direct relation with wound healing process.

PMID- 23113200
TI  - Quality of Life, Motor Ability, and Weight Status among School-aged Children of
      Tehran.
AB  - BACKGROUND: This study aimed to investigate the relationship between health
      Related quality of life (HRQOL), motor ability and weight status in children.
      METHODS: Two hundred forty children ages 9-11 yr who were selected via multi
      stage cluster sampling design from primary schools in the Shahre Qods at Tehran,
      Iran in 2007. HRQOL was assessed by the pediatric quality of life inventory
      (PedsQL). Motor abilities were determined by a Basic Motor Ability Test (BMAT).
      Body mass index was calculated to determine weight status. RESULTS: Psychosocial,
      physical, and total health related qualities of life (all P< 0.05) were
      significantly lowered for obese when compared to normal weight participants. In
      contrast, the mean scores for each HRQOL domain in motor ability category were
      not significant. No significant interaction was apparent when examining HRQOL
      scores, BMAT variables and weight status. CONCLUSION: Regardless of motor ability
      levels, reducing body weight among children is a potential avenue for promoting
      improved HRQOL. Over weight boys reported significantly worse school performance
      than over weight girls, suggesting the importance in considering such dimensions
      in programs aimed at further understanding obesity in children.

PMID- 23113201
TI  - Multidisciplinary approach in diabetic foot care in iran (new concept).

PMID- 23113202
TI  - Nuclear power: is it blessing or disaster in East Asia?

PMID- 23113203
TI  - Towards An Improvement of Hospital Services and Streamlining of Health Care
      Costs: The DRG Analysis in Italy.
AB  - The term Diagnosis-related Group (DRG) refers to a classification system used to
      assess hospital services with the aim of a better management of health care costs
      and improving performance. The DRG system focuses on the utilization of
      resources, and is not concerned with the specific type of care provided to the
      patient. This system highlights any diseconomies and eventual critical aspects of
      the hospital system. This article, starting from the history of heath care
      financing in Italy and pointing out the difficulty to define the "quality" of
      health care services, describes the variables used to evaluate correctly hospital
      performance based on the DRG system. These include Average Length of Stay,
      Average Daily Patient Load, Comparative Performance Index, and Case Mix Index.

PMID- 23113204
TI  - Malaria Status in Economic Cooperation Countries; Achievement and Gaps toward
      United Nations Millennium Development Goals.
AB  - BACKGROUND: Evaluating the malaria status of the Economic Cooperation
      Organization (ECO) member countries relation to goal 6 of 3rd Millennium
      Development Goals (MDGs) which includes have halted by 2015 and begun to reverse
      the incidence of malaria. METHODS: By 2009, we reviewed the MDGs reports,
      extracted the data from surveillance system, published, and unpublished data. The
      main stakeholders, from both governmental and international organizations in the
      country have been visited and interviewed by the research team as part of the
      data validation process. RESULTS: The malaria incidence is very heterogeneous
      among ECO countries, which differ less than 200 cases in total country in
      Kazakhstan, Kyrgyzstan, Turkey, Turkmenistan, Uzbekistan, and Azerbaijan to
      82,564 cases (2,428/100,000) in Afghanistan and 59,284 cases (881/100,000) in
      Pakistan and about 18/100,000 in Iran in 2008. Malaria has been a major public
      health problem in Pakistan and Afghanistan and will continue to pose serious
      threat to millions of people due to poor environmental and socioeconomic
      conditions conducive to the spread of disease. The main malaria endemic areas of
      Iran are in southeastern part of the country; consist of less developed provinces
      that are bordered in the east by Afghanistan and Pakistan. There are little valid
      information about proportion of population in malaria-risk areas using effective
      malaria prevention and treatment measures indicators. CONCLUSION: All ECO
      countries could achieve MDGs malaria indicators by 2015 except Pakistan and
      Afghanistan, unless preparing urgent intervention programs to fulfill the goals.

PMID- 23113205
TI  - Health care financing in iran; is privatization a good solution?
AB  - BACKGROUND: This paper considers a range of issues related to the financing of
      health care system and relevant government policies in Iran. METHODS: This study
      used mixed methods. A systematic literature review was undertaken to identify
      relevant publications. This was supplemented by hand searching in books and
      journals, including government publications. The issues and uncertainties
      identified in the literature were explored in detail through semi-structured
      interviews with key informants. These were triangulated with empirical evidence
      in the form of the literature, government statistics and independent expert
      opinions to validate the views expressed in the interviews. RESULTS: The
      systematic review of published literature showed that no previous publication has
      addressed issues relating to the financing of healthcare services in Iran.
      However, a range of opinion pieces outlined issues to be explored further in the
      interviews. Such issues summarised into four main categories. CONCLUSION: The
      health care market in Iran has faced a period in which financial issues have
      enhanced managerial complexity. Privatization of health care services would
      appear to be a step too far in assisting the system to confront its challenges at
      the current time. The most important step toward solving such challenges is to
      focus on a feasible, relevant and comprehensive policy, which optimises the use
      of health care resources in Iran.

PMID- 23113206
TI  - Computational Prediction of Phylogenetically Conserved Sequence Motifs for Five
      Different Candidate Genes in Type II Diabetic Nephropathy.
AB  - BACKGROUND: Computational identification of phylogenetic motifs helps to
      understand the knowledge about known functional features that includes catalytic
      site, substrate binding epitopes, and protein-protein interfaces. Furthermore,
      they are strongly conserved among orthologs, indicating their evolutionary
      importance. The study aimed to analyze five candidate genes involved in type II
      diabetic nephropathy and to predict phylogenetic motifs from their corresponding
      orthologous protein sequences. METHODS: AKR1B1, APOE, ENPP1, ELMO1 and IGFBP1 are
      the genes that have been identified as an important target for type II diabetic
      nephropathy through experimental studies. Their corresponding protein sequences,
      structures, orthologous sequences were retrieved from UniprotKB, PDB, and PHOG
      database respectively. Multiple sequence alignments were constructed using
      ClustalW and phylogenetic motifs were identified using MINER. The occurrence of
      amino acids in the obtained phylogenetic motifs was generated using WebLogo and
      false positive expectations were calculated against phylogenetic similarity.
      RESULTS: In total, 17 phylogenetic motifs were identified from the five proteins
      and the residues such as glycine, leucine, tryptophan, aspartic acid were found
      in appreciable frequency whereas arginine identified in all the predicted PMs.
      The result implies that these residues can be important to the functional and
      structural role of the proteins and calculated false positive expectations
      implies that they were generally conserved in traditional sense. CONCLUSION: The
      prediction of phylogenetic motifs is an accurate method for detecting
      functionally important conserved residues. The conserved motifs can be used as a
      potential drug target for type II diabetic nephropathy.

PMID- 23113207
TI  - Sexual education in malaysia: accepted or rejected?
AB  - BACKGROUND: Introduction to sexual education in schools was suggested by the
      Malaysian government as one of the effort taken in the aim to reduce the sexual
      related social problems among Malaysian teenagers nowadays. This study was
      proposed in the aim to determine the rate of acceptance among adolescents on the
      implementation of sexual education in schools. METHODS: This study was conducted
      using questionnaires distributed to 152 pre-degree students in Faculty of
      Pharmacy, Universiti Teknologi MARA (UiTM), Kampus Puncak Alam, Selangor,
      Malaysia. Obtained data were statistically analyzed. RESULTS: Almost half (49.3%)
      of the respondents agreed that sexual education might help to overcome the social
      illness among school teenagers. Besides, a large number (77.6%) of respondents
      also agreed that this module should be incorporated with other core subjects
      compare to the feedback received on the implementation of this module on its own
      (28.9%). CONCLUSION: These results have provided some insight towards the
      perception of sexual education among the teenagers. Since most of the respondents
      agreed with this idea, so it might be a sign that the implementation of sexual
      education is almost accepted by the adolescents.

PMID- 23113208
TI  - Edentulousness, denture wear and denture needs of the elderly in rural South
      India.
AB  - BACKGROUND: The objectives of this study were to evaluate the prevalence of
      edentulousness, patient's perception on dietary changes resulting from tooth loss
      and to identify the disparity between actual and patient perceived need to
      replace missing teeth in an elderly rural population in south India. METHODS: A
      cross sectional study using the systematic cluster sampling method was used to
      select the study sample of 150 elderly men and women. Data were collected using
      questionnaires and oral examination. The data were statistically analyzed using
      chi square test and pearson correlation. RESULTS: 15.6% of the rural elderly were
      completely edentulous and 54.7% were partially edentulous. Observed differences
      in distribution between the sampled elderly age groups were found to be
      statistically significant. Although 70.3% of the evaluated elderly actually
      required prosthodontic treatment, only 14.4% perceived the need to replace
      missing teeth. A small percentage of the elderly (18%) perceived a severe change
      in their diets due to tooth loss. Thirty three percent of them perceived a
      moderate change and 28% felt that there were no dietary changes because of tooth
      loss. CONCLUSIONS: It is essential to identify feasible strategies to provide
      primary dental health education and treatment to all rural elderly in the future.
      We suggest community dental health services as a general health need of the
      elderly rather than a special health need of the community.

PMID- 23113209
TI  - Evidence of adverse selection in Iranian supplementary health insurance market.
AB  - BACKGROUND: Existence or non-existence of adverse selection in insurance market
      is one of the important cases that have always been considered by insurers.
      Adverse selection is one of the consequences of asymmetric information. Theory of
      adverse selection states that high-risk individuals demand the insurance service
      more than low risk individuals do. METHODS: The presence of adverse selection in
      Iran's supplementary health insurance market is tested in this paper. The study
      group consists of 420 practitioner individuals aged 20 to 59. We estimate two
      logistic regression models in order to determine the effect of individual's
      characteristics on decision to purchase health insurance coverage and loss
      occurrence. Using the correlation between claim occurrence and decision to
      purchase health insurance, the adverse selection problem in Iranian supplementary
      health insurance market is examined. RESULTS: Individuals with higher level of
      education and income level purchase less supplementary health insurance and make
      fewer claims than others make and there is positive correlation between claim
      occurrence and decision to purchase supplementary health insurance. CONCLUSION:
      Our findings prove the evidence of the presence of adverse selection in Iranian
      supplementary health insurance market.

PMID- 23113210
TI  - Better mental component of quality of life in amputee.
AB  - BACKGROUND: Assessment of quality of life can promote health services. The
      purpose of this study was evaluation of health related quality of life in lower
      limbs amputee veterans of Iran. METHODS: In the present cross sectional study, we
      compared 38 lower limbs amputee veterans with 50 normal healthy subjects with
      SF36 questioner in face-to-face interview. RESULTS: Amputees had significantly
      lower grade than normal subject did in role physical (P < 0.01) and were better
      than normal subjects in vitality (P < 0.001) and mental health (P < 0.01). As a
      whole, amputees have higher in mental summary component of quality of life (P <
      0.05) and lower in physical component of quality of life (P < 0.01). CONCLUSION:
      Diminishing the demand and improving social support of amputee veterans might be
      considered as high grade in mental summary component of their quality of life.

PMID- 23113211
TI  - Reference Intervals for Serum Immunoglobulins IgG, IgA, IgM and Complements C3
      and C4 in Iranian Healthy Children.
AB  - BACKGROUND: Determination of reference ranges of each serum protein in normal
      population of each country is required for studies and clinical interpretation.
      The aim of this study was defining reference range values of immunoglobulins and
      complement components in Iranian healthy children. METHODS: This study was
      conducted from June 2003 to June 2006 in Immunology, Asthma and Allergy Research
      Institute, Tehran University of Medical Sciences. Serum levels of IgG, IgM, IgA,
      C3 and C4 in 800 Iranian healthy children from newborn to 18 years of age in four
      population were measured by nephelometry. Kolmogrov-Smirnov tests and Pearson
      correlation tests were used for analysis. RESULTS: Our results mainly agree with
      previous reports, except for some discrepancy that might be due to the ethnic and
      geographic variety. There was a significant difference between two sexes only
      with IgA in the group of 1-3 months old, which was higher in male group and IgM
      in groups of 3-5, 6-8 and 9-11 years old that were higher in female groups. Mean
      of other serum immunoglobulins and complements was not significantly different
      between male and female groups. CONCLUSION: These results can be considered as a
      local reference for use in laboratories, clinical interpretations, and research
      for Iranian children.

PMID- 23113212
TI  - Developing the use of quality indicators in sterilization practices.
AB  - BACKGROUND: Health-care-associated infections are a major threat to the safety of
      patient care. Control of such problem is a major criterion for hospital
      accreditation. This study was aimed to determine the developing use of chemical
      (class 6 products) and biological indicators in Tabriz district hospitals since
      1997 to 2011. METHODS: We conducted this time-trend interventional study with all
      of the public and private hospitals, which counted to 21 in Tabriz district as a
      sample. The situations of indicator use were presented for each time in the base
      of indicator groups. Furthermore, the results were showed in the base of hospital
      groups. RESULTS: All of district hospital (n=21) with 74 autoclave machine and 22
      central sterilization room were studied. The result of second time study in 2008
      showed a markedly improvement in the control of sterilization processes.
      Furthermore, we continued our intervention results 6 month later in 2009 and 2
      years later in 2011. The most striking result were use of chemical indicator in
      100% of hospitals. However, there are defects in the use of biological indicators
      (63.65%). CONCLUSION: The most obvious finding was significant improvement in
      sterilization control especially in development the use of chemical indicators.
      The finding of this study has a number of important implications for hospital
      managers and infection control practitioners such as continuous practical
      training of CSSD personnel in hospitals and mandating of indicator using in all
      sterilization process with controlling of this subject in evaluation and
      accreditation of hospital programs.

PMID- 23113213
TI  - Mycological Microscopic and Culture Examination of 400 Bronchoalveolar Lavage
      (BAL) Samples.
AB  - BACKGROUND: The frequency of invasive opportunistic mycoses has increased
      significantly over the past decades especially in immunocompromised patients.
      Invasive aspergillosis (IA) has become a major cause of morbidity and mortality
      among these patients. As bronchoalveolar lavage (BAL) fluid samples are generally
      useful specimens in the diagnosis of invasive pulmonary aspergillosis (IPA), this
      study was designed to evaluate the incidence of fungal elements in at-risk
      patients by direct microscopy and culture of BAL samples. METHODS: In a 16-month
      period, 400 BAL samples were obtained from several groups of different patients
      with pulmonary and respiratory disorders and examined by using both direct
      microscopy and culture. RESULTS: Of the 400 samples, 16 (4%) were positive direct
      examination with branching septate hyphae and 46 (11.5%) were positive culture:
      25 (54%) Aspergillus flavus, 6 (13%) A. fumigatus, 5 (10.9%) A. niger, 1 (2.2%)
      A. terreus, 3 (6.5%) Penicillium spp. and 6 (13%) mixed A. flavus/A. niger. A.
      flavus was the most common cause of Aspergillus infection or colonization. Bone
      marrow transplant (BMT) recipients were the most susceptible group to fungal
      infection and/or colonization. CONCLUSION: Among Aspergillus species, A. flavus
      was the most common isolate in both infections and colonization in Iran. More
      studies are needed to clarify the epidemiological aspect of aspergillosis in
      Iran.

PMID- 23113215
TI  - First Record of Co - infection of Three Clinostomatid Parasites in Cichlids
      (Osteichthyes: Cichlidae) in a Tropical Freshwater Lake.
AB  - The present study investigated the effects of first record of co-infection of
      three Clinostomum sp.; Clinostomum Complanatum (Rudolphi, 1819), C. tilapiae
      (Ukoli, 1966), and Euclinostomum hetereostomum (1809) in Tilapia zilii. There was
      differential parasitic effects resulting in selection for relatively better
      adaptiveness to host's microhabitats, more population size, and frequent host
      location of these parasites during the one year survey (Nov 2007-Oct 2008) in Opi
      Lake, Nigeria. Prevalence of 9.4 % was recorded in C. complanatum, 10.4 % in E.
      heterostomum and 4.8% in C. tilapiae. The parasites were recovered from three
      major microhabitats of buccal cavity, skin and eye.

PMID- 23113214
TI  - Risk factors of non-communicable diseases and metabolic syndrome.
AB  - BACKGROUND: Metabolic syndrome is a common nmetabolic ndisorder, which leads to
      early Cardio Vascular Disease and diabetes type II. The goal of this study was to
      determine the prevalence of metabolic syndrome and its risk factors in Kurdistan,
      Iran. METHOD: The data was extracted from provincial section of Iranian national
      non-communicable surveillance survey conducted in 2005. The study was a
      population-based survey with multi-stage cluster sampling method. Adult Treatment
      Panel-III measures were used for assessing the prevalence of metabolic syndrome
      among residents of Kurdistan Province aged 25 to 64 yr. EPI-Info 6 was used to
      enter the data and the data was analyzed using SPSS 11.5. RESULTS: Totally, 1194
      participants were recruited in our survey. The prevalence of metabolic syndrome
      was 29.1%. The prevalence was 41.3% among women and 17.1% among men (P= 0.001).
      As we go higher among age groups, the prevalence increases. CONCLUSION: This is
      the first study to investigate the metabolic syndrome in Kurdistan and Kurd
      ethnicity. The high level of metabolic syndromes prevalence especially among
      women shows the need and importance of suitable and effective preventive
      programs. These preventive programs must promote changes in lifestyle, especially
      with respect to nutrition, physical activities, and control of blood pressure.

PMID- 23113216
TI  - Coincidence of trisomy 18 and robertsonian (13; 14).
AB  - This case report presents a coincidence of trisomy 18 and balanced Robertsonian
      translocation (13;14). Aneuploidy was suspected based on anomalies detected in
      ultrasound scan and confirmed with karyotype. In a 31 years-old healthy woman
      with a history of one miscarriage, second trimester ultrasound scan reported IUGR
      (<3rd percentile) with normal amniotic fluid, bilateral choroid plexus cysts,
      suspicious agenesis of corpus callosum and clenched hands. Amniocentesis was
      performed and karyotype was 46xx,der(13;14) (q10;q10),+18. Maternal karyotype was
      45xx,der(13;14)(q10;q10). Pregnancy was continued due to legal limitation for
      termination after 20 weeks gestation. Delivery was done at 36 weeks gestation. A
      female newborn was borned and a physical feature was hypotonia, small mouth,
      prominent occiput, low-set and posteriorly rotated ears, clenched hands with
      overlapping fingers and rocker bottom feet. Ultrasound scan and echocardiography
      detected agenesis of corpus callosum and VSD, ASD, PDA and cardiomegaly. These
      features are typical of trisomy 18. Balanced Robertsonian translocation usually
      has no phenotypic expression. Genetic counseling and prenatal diagnosis for
      future pregnancy was recommended.

PMID- 23113217
TI  - Toward Competence-based Education: Time to Update Dentistry Content of Medical
      Curricula in Iran.

PMID- 23113218
TI  - Medical Tourist's Perception in Selecting their Destination: A Global
      Perspective.
AB  - BACKGROUND: The need for better healthcare has grown significantly in recent
      years. In addition, the rising healthcare costs in the U.S. and in many European
      countries have forced many patients to seek medical treatment abroad, which has
      created the demand for medical tourism. With little yet known as to the
      perception of a medical tourist's destination selection, this study aims to
      explore medical tourist's perception in selecting their destination while going
      for medical treatment. METHODS: Realizing the current need to examine closely the
      perception of medical tourists, this study had conducted a secondary study to
      collect data for assessing and identification of the key factors on patient's
      perception and destination selection criteria. RESULTS: The result confirms the
      existence of a very strong relationship between cost, service quality, treatment
      types and availability and marketing impact on the perception of the medical
      tourists' in selecting their medical tourism destination. CONCLUSION: This study
      offers support for the proposed conceptual model and an empirical basis for
      comparison in future research.

PMID- 23113219
TI  - Iron, iodine and vitamin a in the middle East; a systematic review of deficiency
      and food fortification.
AB  - BACKGROUND: Micronutrient deficiency is one of the major public health problems
      in the Middle East affecting economic, political and social development of
      countries. The three commonest micronutrient deficiencies belong to iron, iodine
      and vitamin A. METHODS: we conducted a systematic review of published English
      articles in the Middle East countries using databases from PubMed, World Health
      Organization and Food and Agriculture Organization from 1985 onward. A total of
      6050 articles were identified and after evaluation based on eligibility criteria,
      81 articles included in this systematic review. RESULTS: Despite implementation
      of flour fortification other control strategies, the prevalence of iron
      deficiency is moderate to severe in the Middle Eastern countries, because of
      ineffective iron fortification program, food interaction and hemoglobin
      application as anemia indictors in these countries. Mild to severe iodine
      deficiency disorders exist in many countries of the Middle East, due to lack of
      effective iodine supplementation program. The prevalence of vitamin A deficiency
      is mild to severe and there is lack of vitamin A fortification program in many
      countries in this region. CONCLUSION: Despite unharmonized efforts to control
      malnutrition of micronutrients, iron, iodine and vitamin A deficiencies are still
      exist in some countries of the Middle East. Effective, well controlled and
      harmonized programs for elimination of micronutrient deficiencies need to be
      initiated for governments and supported by international organizations in this
      region.

PMID- 23113220
TI  - Effects of combined exercise training on body composition and metabolic syndrome
      factors.
AB  - BACKGROUND: Metabolic syndrome (MS) is emerging as a serious public health
      problem in Korea. The purpose of this study was to examine the effects of 12
      weeks of combined exercise training on body composition and MS factors in obese
      Korean female college students. METHODS: Subjects were randomly assigned to
      exercise (n = 7) and control (n = 9) groups. The exercise group trained for 80
      min/day, for 3 day/week for 12 weeks. Each exercise session comprised 3 phases:
      warm-up for 10 min, main exercise for 60 min (consisting of aerobic exercise for
      30 min and resistance exercise for 30 min), and cool down for 10 min. RESULTS:
      The exercise intensity for aerobic exercise was 60-80% of the heart rate reserve
      (HRR) for 30 min, while the resistance exercises were 10-15 repetitions maximum
      (RM) for 30 min. Two-way repeated analysis of variance (ANOVA) was used for
      statistical analysis. There were no interaction effects (time * group) on the MS
      related factors of blood lipid composition such as triglycerides (TGs), high
      density lipoprotein (HDL), glucose, total cholesterol (TC), and low-density
      lipoprotein (LDL). However, interaction effects were observed (time * group) on
      percent body fat (P = 0.006), waist circumference (WC; P < 0.001), systolic blood
      pressure (SBP; P = 0.010), and diastolic blood pressure (DBP; P = 0.007).
      CONCLUSIONS: A 12-week supervised combined exercise program could effectively
      reduce percent body fat, WC, SBP, and DBP. However, it was not effective on MS
      related factors of blood lipid composition such as TG, HDL, glucose, TC, and LDL
      in a sample population of obese Korean female college students.

PMID- 23113221
TI  - Prevalence of elder abuse and neglect in seniors with psychiatric morbidity -
      example from central moravia, czech republic.
AB  - BACKGROUND: Elder abuse and neglect (EAN) comprises emotional, financial,
      physical, and sexual abuse, neglect by other individuals, and self-neglect. Elder
      abuse and neglect in seniors with psychiatric morbidity was not monitored in the
      Czech Republic at all, despite the literature shows mental morbidity as one of
      the important risk factor for developing elder abuse and neglect. METHODS: We
      designed comparative cross sectional study comprising 305 seniors hospitalized in
      Mental Hospital Kromeriz in June 2011 - group of 202 seniors hospitalized due to
      mental disorder in psychogeriatric ward and group of 103 seniors hospitalized due
      to somatic disorder in internal ward. Content analysis of medical records was
      done in both groups of seniors, with regards to symptoms of elder abuse. Then, we
      discussed the topic of elder abuse with 30 nurses of psychogeriatric ward in
      focus group interview. RESULTS: Between two compared groups of seniors we
      detected statistically higher prevalence of elder abuse in seniors with
      psychiatric morbidity (48 cases, 23.8% prevalence of EAN), compared to
      somatically ill seniors (3 cases, 2.9%). As for nursing staff, 5 from 30 nurses
      (16.7%) have never heard about symptoms of elder abuse and neglect, 10 from 30
      nurses (33.3%) had just a partial knowledge about elder abuse and neglect and its
      symptoms, the rest of nurses (15 from 30 nurses, 50.0%) had good knowledge about
      elder abuse and neglect and its symptoms. CONCLUSION: Elder abuse and neglect
      seems to be a relevant problem in senior population with mental disorders.
      Development of educational programs for nursing and medical staff about Elder
      abuse and neglect (symptoms of EAN, early detection of EAN, knowledge how to
      report cases of EAN) could improve the situation and help mentally ill seniors to
      better quality of life.

PMID- 23113222
TI  - Serum uric Acid level and diverse impacts on regional arterial stiffness and wave
      reflection.
AB  - BACKGROUND: Both increased arterial stiffness and hyperuricaemia are associated
      with elevated cardiovascular risks. Little is known about the relations of serum
      uric acid (UA) level to regional arterial stiffness and wave reflection. The aim
      of the study was to investigate the gender-specific association of serum UA and
      indices of arterial function in a community-based investigation in China.
      METHODS: Cross-sectional data from 2374 adults (mean age 58.24 years) who
      underwent routine laboratory tests, regional pulse wave velocity (PWV) and pulse
      wave analysis measurements were analyzed in a gender-specific manner. None of the
      participants had atherosclerotic cardiovascular disease, chronic renal failure,
      systemic inflammatory disease, gout, or were under treatment which would affect
      serum UA level. RESULTS: Men had higher serum UA level than women. Subjects with
      hyperuricaemia had significantly higher carotid-ankle PWV in both genders (P<
      0.05), and the carotid-femoral PWV (PWVc-f) was higher in women (P< 0.001) while
      the augmentation index was marginally lower in men (P = 0.049). Multiple
      regression analysis showed that serum UA was an independent determinant only for
      PWVc-f in women (beta = 0.104, P = 0.027) when adjusted for atherogenic
      confounders. No other independent relationship was found between UA level and
      other surrogates of arterial stiffness. CONCLUSIONS: Serum UA levels are
      associated with alterations in systemic arterial stiffness that differ in men and
      women. Women might be more susceptible to large vascular damage associated with
      hyperuricaemia.

PMID- 23113224
TI  - Estimating the proportion of diabetes to the attributable burden of
      cardiovascular diseases in iran.
AB  - BACKGROUND: This study aimed at estimating the proportion of diabetes as a risk
      factor to the attributable burden of cardiovascular diseases in Iran. METHODS:
      Comparative Risk Assessment methodology was used to calculating Potential Impact
      Fraction (PIF). To calculate PIF, data on the prevalence of newly diagnosed
      diabetes mellitus (NDM) and known diabetes mellitus (KDM) were obtained from 3rd
      Iranian surveillance of risk factors of non-communicable diseases and data on
      corresponding measures of effect were derived from a cohort study. PIF were
      estimated on both theoretical minimum and feasible minimum risk. Uncertainty for
      the attributable burden was estimated by Monte Carlo simulation-modeling
      techniques incorporating sources of uncertainty. RESULTS: According to
      multivariate-adjusted hazard ratios, by reducing the prevalence of Iranian women
      with diabetes from 10.05 percent to the feasible minimum risk level i.e. 5
      percent, 6.8% (95% uncertainty intervals: 3.5-9.8) of attributable Disability
      Adjusted Life Years (DALYs) to CVD are avoidable and the corresponding value for
      men were 3.1% (95% uncertainty intervals: 1.4-4.8). CONCLUSION: Although data on
      the prevalence of diabetes and corresponding measures of associations were
      obtained from an updated and country-specific source, but to better priority
      setting, PIF should be applied to updated and revised burden of CVDs.

PMID- 23113223
TI  - Patient experience of nursing quality in a teaching hospital in saudi arabia.
AB  - BACKGROUND: Examining the quality of nursing care from the patient's perspective
      is an important element in quality evaluation. The extent to which patients'
      expectations are met will influence their perceptions and their satisfaction with
      the quality of care received. METHODS: A cross-sectional survey was conducted
      among admitted patients at King Khalid Teaching Hospital, Riyadh, Saudi Arabia.
      Data were collected (from January 2011 to March 2011) from a convenience sample
      of 448 patients using a 42-items questionnaire assessing six dimensions of the
      nursing care provided to, during hospitalization. RESULTS: On a four-point scale
      (4-higly agree,3-agree, 2-disagree, and 1-higly disagree). The individual items
      of nursing care showing the lowest means were the information received from the
      nurses about self-help (2.81), the information about the laboratory results
      (2.76) and the way the nurse shared the patient's feeling (2.72). A strong
      correlation existed between the overall perception level and the variables of
      gender (P=0.01), and the types of department (0.004). CONCLUSION: The findings of
      this study demonstrate negative experiences of patients with nursing care in
      dimensions of information, caring behavior, and nurse competency and technical
      care. Awareness of the importance of these dimensions of nursing care and ongoing
      support to investigate patients' perception periodically toward quality of
      nursing care are critical to success the philosophy of patient centered health
      care.

PMID- 23113225
TI  - Evaluation of Accessibility of Iodinated Salt and Nutritional Iodine Status
      during Pregnancy.
AB  - BACKGROUND: To assess accessibility of iodinated salt and urinary iodine
      concentrations (UIC) during pregnancy. This cross-sectional study was carried out
      between October and December, 2009 in Urmia County, West Azerbaijan (WA), Iran.
      METHODS: Data on demographic characteristics and iodinated salt accessibility
      were gathered through a questionnaire at 1st trimester. Household salt samples
      and urine samples (1st -and 3rd trimesters) were analyzed for iodine content.
      Pregnant women (n=490) at 1st trimester were interviewed. Of these, 490 subjects
      (12 prenatal care centers) were enrolled. RESULTS: All participants declared that
      they were exclusive users of iodinated salt. Segregation of the household salt
      samples according to iodine content (0, 8, 15 and 30 ppm) revealed that the
      respective distributions were 3.3%, 1.4%, 23.7% and 71.6%. Median UIC levels at
      1st and 3rd trimesters were 73.5 MUg/L and 114MUg/L respectively. Accordingly,
      86% and 70% of participants exhibited UIC < 150 MUg/L. CONCLUSION: Median UIC
      during pregnancy in WA is markedly lower than those previously reported for
      regions with adequate iodine status in the country. Thus, extra iodine is needed
      to maintain adequate iodine store during gestation. In addition, this preliminary
      study reveals that a significant proportion (28%) of the household salt samples
      had low iodine content (<= 15 ppm) although a level (>20 and <40 ppm) is
      mandatory in Iran. Further studies are deemed necessary to elucidate the cause(s)
      for manifestation iodine deficiency among pregnant women despite 20 years after
      iodine fortification strategy.

PMID- 23113226
TI  - Assessment of welders exposure to carcinogen metals from manual metal arc welding
      in gas transmission pipelines, iran.
AB  - BACKGROUND: Welding can produce dangerous fumes containing various metals
      especially carcinogenic ones. Occupational exposure to welding fumes is
      associated with lung cancer. Therefore, welders in Gas Transmission Pipelines are
      known as a high-risk group. This study was designed to determinate the amounts of
      metals Cr, Ni, and Cd in breathing zone and urine of welders and to assess the
      possibility of introducing urinary metals as a biomarker due to occupational
      exposure. METHODS: In this cross sectional study, 94 individuals from Gas
      Transmission Pipelines welders, Iran, Borujen in 2011 were selected and
      classified into 3 groups including Welders, Back Welders and Assistances. The
      sampling procedures were performed according to NIOSH 7300 for total chromium,
      nickel, and cadmium and NIOSH 7600 for Cr+6. For all participants urine samples
      were collected during the entire work shift and metals in urine were determined
      according to NIOSH 8310. RESULTS: Back Welders and Assistances groups had maximum
      and minimum exposure to total fume and its elements, respectively. In addition,
      results showed that there are significant differences (P<0.05) between Welders
      and Back Welders with Assistances group in exposure with total fume and elements
      except Ni. Urinary concentrations of three metals including Cr, Cd and Ni among
      all welders were about 4.5, 12 and 14-fold greater than those detected in
      controls, respectively. Weak correlations were found between airborne and urinary
      metals concentrations (R2: Cr=0.45, Cd=0.298, Ni=0.362). CONCLUSION: Urinary
      metals concentrations could not be considerate as a biomarker for welders'
      exposure assessment.

PMID- 23113227
TI  - Enteroviruses in acute myocardial infarction.
AB  - BACKGROUND: Human enteroviruses (EVs) may have a role as a possible risk factor
      in the pathogenesis of MI. The aim of this study was to evaluate the presence of
      enterovirus genomic RNA in peripheral blood samples of patients with acute
      myocardial infarction (MI). METHODS: We investigated the presence of enterovirus
      genomic RNA in the peripheral blood of 115 patients with acute MI hospitalized in
      the Coronary Care Unit of Imam Reza and Ghaem University Hospitals (Mashhad,
      Iran) by RT-PCR using the virus specific primers. RESULTS: The subjects' mean (+/
      SD) age was 63.5 (+/-9.4) years (range: 38-82) and 38.3 % of the subjects were
      female. Of 115 patient specimens, 3 (2.6%) were positive in RT-PCR. CONCLUSION:
      The prevalence of enterovirus in MI patients is considerable. More investigations
      are needed to determine the causal role of enteroviruses in MI.

PMID- 23113228
TI  - Seroepidemiology of herpes simplex virus type 1 and 2 in northern iran.
AB  - BACKGROUND: Herpes simplex virus (HSV) type 1 and 2 are common infectious agents
      worldwide. Data on prevalence of HSV-1 and HSV-2 infection are limited in Asia,
      especially in Iran. The aim of this study was to determine the seroprevalence of
      HSV type 1 and 2 based on age, gender, marital status, education, living area,
      job, symptoms and history of disease variables. METHODS: The study population
      included 800 randomly selected persons from laboratories in Gilan Province, Iran,
      from 2010 to 2011. Demographic data gathered by a well-designed questionnaire and
      for serological studies, blood samples were collected and centrifuged. ELISA HSV
      1, 2 and HSV-2 specific ELISA kits were used to determine IgG type specific
      antibodies in sera samples. Person's chi-square test was applied to compare HSV-1
      and HSV-2 seropositivities. RESULTS: HSV-1 and HSV-2 IgG antibodies were positive
      in 467 (58.4%) and 28 (3.5%) subjects, respectively. There was significant
      correlation between age, marital status, job, symptoms, history of disease and
      HSV seroprevalence (P<0.05). CONCLUSION: Our findings were in agreement with
      prior studies in which HSV-1 infections was more prevalent than HSV-2 and
      seropositivity increased with age.

PMID- 23113229
TI  - Efficacy of Microwave and Infrared Radiation in the Treatment of the Skin Lesions
      Caused by Leishmania major in an Animal Model.
AB  - BACKGROUND: Cutaneous leishmaniasis caused by L. major is an important public
      health problem in endemic areas. The aim of this study was to explore the
      therapeutic effect of microwave and or infrared radiation in the treatment of
      lesion induced in BALB/c mice by L. major inoculation. METHODS: The footpad
      lesion was induced in BALB/c mice by inoculation of L. major promastigotes
      subcutaneously. The lesion was treated with 600 watts power, 2.450 GHz frequency
      and/or infrared device with 150 watts and a wave length of 890 nanometres. The
      size of the lesion was recorded by footpad swelling measurement every 10 days.
      RESULTS: The lesion growth was significantly hampered in treated mice compared
      with the untreated control group (P<0.05). Infrared radiation was more effective
      than microwave in inhibiting ulcer enlargement. CONCLUSION: Infrared radiation
      and microwave significantly hampered L. major lesion growth in BALB/c mice. This
      therapeutic effect was more in infrared radiation treated mice than microwave
      treated mice.

PMID- 23113230
TI  - Identification of Prototheca zopfii from Bovine Mastitis.
AB  - BACKGROUND: The aim of this study was identification of the epidemiology of
      Prototheca zopfii species from the milk samples of dairy cattle in Isfahan,
      central Iran. METHODS: Milk samples were obtained from 230 dairy cattle, 130 with
      and 100 without mastitis, in Isfahan. The samples were cultured in Prototheca
      Isolation Medium (PIM) and Sabouraud's dextrose agar. All P. zopfii isolates were
      identified by morphological and biochemical methods. Then, as a confirmatory test
      they were examined by genotype-specific PCR. RESULTS: Four P. zopfii strains
      (3.07%) were isolated from the 130 samples of dairy cattle with clinical mastitis
      and there was no isolation from totally 100 samples of healthy bovines without
      mastitis. Specific PCR product (about 946 bp) was detected in four isolates.
      CONCLUSION: It seems that P. zopfii genotype II plays a key role in affecting
      bovine mastitis that confirmed other previous studies. Our study was the first,
      which identified the Prototheca species by traditional and molecular methods in
      Iran and Middle East as well.

PMID- 23113231
TI  - Overview of blood transfusion system of iran: 2002-2011.
AB  - Despite importance of blood transfusion services as life saving procedures, some
      countries are unable to meet their national requirements for blood and blood
      components in a timely manner. Since establishment of Iran Blood Transfusion
      Organization (IBTO) in 1974 as an integral part of national health system, Iran
      has experienced a drastic improvement both in availability and safety of blood
      and blood products. Iran now has not only reached to a 100% non remunerated
      voluntary blood donation but also secured a national self sufficiency of blood
      and blood components. Efforts of IBTO as the sole player of transfusion medicines
      in Iran enabled the country for timely providing of life saving blood transfusion
      services for all Iranian patients in need of such services. In order to meet the
      country's demand in 2011 about 2 million units of whole blood for a population of
      about 75 million collected by IBTO. This indicates 26.2 donations per 1000
      population. Currently about 94% of blood donors in Iran are 25-35 years old males
      and contribution of female donors in blood donation is less than 6%. IBTO screen
      all donated blood for important transfusion transmissible infections such as HBV,
      HIV, HCV and syphilis. Prevalence of HBsAg, HCV and HIV in donated blood in IBTO
      in 2011 was 0.20%, 0.06% and 0.004% respectively.

PMID- 23113232
TI  - Increased 5-bromo-2'-deoxyuridine incorporation in various brain structures
      following passive avoidance training in mice.
AB  - We studied the effects of training on DNA synthesis intensity in mouse brain.
      Brain cells where DNA synthesis-associated processes took place under the
      influence of training were detected by immunohistochemical labeling of DNA
      molecules with synthetic thymine analogue 5-bromo-2'-deoxyuridine. The number of
      5-bromo-2'-deoxyuridine-positive cell increased in various structures of the
      brain under the influence of training.

PMID- 23113233
TI  - Detection of trace processes in the networks of neurons cultured on
      microelectrode arrays.
AB  - We compared the effects of electrical stimulation of primary dissociated neuronal
      cultures cultured on microelectrode arrays in terms on the expression of c-fos
      transcriptional factor that is involved in plastic reorganization in neurons.
      Dissociated hippocampal neurons cultured on multielectrode arrays were exposed to
      two stimulation protocols: high-frequency and low-frequency stimulations.
      Expression of c-fos was evaluated using immunofluorescence. Both high-frequency
      and low-frequency stimulations significantly increased c-fos expression in
      comparison with non-stimulated control. These findings indicate that c-fos
      expression can be induced in neuronal cell culture by different types of
      electrical stimulations and can be used for studying plasticity processes in
      microphysiological in vitro systems.

PMID- 23113234
TI  - Heart rate variability during "alarm stage" of burnout syndrome in emergency
      doctors.
AB  - The parameters of heart rate variations were examined in emergency care doctors
      that demonstrated the initial signs of defensive psychological burnout syndrome
      related to their professional activity. These parameters were compared within
      each of two groups with different individual typological features. The
      differences in the heart rate variability parameters were revealed between the
      examinees that were at the compensation or alarm stages of the burnout syndrome.

PMID- 23113235
TI  - Spectral-coherent characteristics of EEG alpha rhythm in different efficiency of
      visual spatial task performance in humans.
AB  - We studied spectral-coherent characteristics of EEG alpha rhythm in 26 students
      demonstrating different performance efficiency in visual spatial tasks of the
      same difficulty. More close coherence of biopotentials in the alpha EEG frequency
      band was observed between the occipital, parietal, central, and temporal areas in
      both hemispheres of the brain. The results of the experiments showed that
      different performance efficiency in visual spatial task of the same difficulty
      was associated with different levels of biopotential synchronization in the EEG
      alpha frequency band.

PMID- 23113236
TI  - Delayed effects of NMDA receptor antagonist MK-801 on storage and reconsolidation
      of spatial memory in rats.
AB  - We studied the effects of NMDA receptor antagonist MK-801 on the storage and
      reconsolidation of spatial memory in Morris water maze in adult rats. MK-801 (50
      MUg/kg) administered 24 h after the completion of training was shown to improve
      the resistance of spatial memory to spontaneous extinction, while reminder
      against the background of MK-801 suppresses its ameliorating effect on memory
      storage. The detected behavioral effects of MK-801 persisted over 60 days after
      administration and can be associated with its influence on coupled
      neurogenesis/apoptosis processes induced during memory trace formation in adult
      animals.

PMID- 23113237
TI  - Mechanisms of amnesia induced by impairment of long-term memory reconsolidation
      in edible snail.
AB  - Involvement of neurotransmitter receptors and translation and transcription
      processes in reconsolidation of conditioned food aversion memory was investigated
      in experiments on edible snails. Injections of neurotransmitter receptor
      antagonists and protein synthesis inhibitors before the reminder session were
      found to induce amnesia that was characterized by the possibility of memory
      recovery in repeated training and under the effect of mnemotropic agent D
      cycloserine (early stage of amnesia) or by resistance to the mentioned actions
      (late stage). It has been shown that amnesia induction by memory reconsolidation
      impairment by neurotransmitter receptor antagonists depends on synthesis of
      specific proteins and mRNA, similar to the cases of induction of other adaptive
      brain modifications.

PMID- 23113238
TI  - Neuronal activity in the dorsal hippocampus after lateral hypothalamus
      stimulation: effects of delta-sleep-inducing peptide.
AB  - We studied central effects of delta-sleep-inducing peptide in the mechanisms of
      positive emotional state formation in rats. In Wistar rats preliminary tested in
      an open field, the reactions of 57 neurons of the dorsal hippocampus were
      analyzed during lateral hypothalamus stimulation and microionophoretic
      application of delta-sleep-inducing peptide. It was found that the number of
      neurons not responding to stimulation in the lateral hypothalamus surpassed the
      number of sensitive neurons (63 and 37%, respectively). Hippocampal neurons in
      active animals were less sensitive to stimulation of the lateral hypothalamus
      than in passive rats (33 vs. 42%) After application of delta-sleep-inducing
      peptide, only 28% neurons responded to stimulation. Thus, delta-sleep-inducing
      peptide reduced the sensitivity of hippocampal neurons to stimulation of the
      lateral hypothalamus.

PMID- 23113239
TI  - Long-term spatial memory retrieval at different times following formation in
      single session training in rats.
AB  - The dynamics of retrieval of spatial memory formed in single-day training in rats
      was studied at different terms after training. Good learners, i.e. rats
      successfully learned to find the hidden platform in the Morris water maze after
      single-day training session, demonstrated spontaneous improvement of maze
      performance on day 5 after training in comparison with that in 24 h after
      training. Poor learners (maze performance during learning session did not differ
      from random level) demonstrated spontaneous improvement of maze performance by
      day 20 after training. These findings attest to the existence of multiple
      mechanisms of memory trace transformation at delayed terms after training.

PMID- 23113240
TI  - Involvement of Wulst neurons in hiding reaction of pied flycatcher nestlings with
      different visual afferentation.
AB  - We studied transcriptional activity in the higher avian center visual system
      (Wulst area) in acoustically guided defensive behavior in visually deprived and
      non-deprived nestlings to evaluate the effects of visual afferentation on
      functional involvement of visual structures in acoustically guided defensive
      behavior. Exclusion of visual afferentation from already formed defensive
      behavior did not significantly change immunoreactivity of Wulst neurons, which
      attests to substantial contribution of other, non-visual, activating influences.
      Limitation of visual afferentation during the formation of defensive behavior
      decreased immunoreactivity of Wulst neurons. Dendritic sprouting in Wulst neurons
      of visually deprived nestlings unable to promote the formation of complex
      interneuronic interactions.

PMID- 23113241
TI  - Free and protein-bound angiotensin II(1-7)in the regulation of drinking behavior
      and hemodynamics in rats.
AB  - We compared physiological activity of synthetic analogues of endogenous protein
      peptide compounds, complexes of angiotensin II(1-7)with functionally different
      proteins (transport protein, serum albumin; and neurospecific Ca(2+)-binding
      protein, S100b). Physiological activity of angiotensin II(1-7)was shown to depend
      on the type of a carrier protein. Our results suggest that complexes of
      angiotensins with BSA and S100b are strong factors for the integration of central
      and peripheral functions at the homeostatic and behavioral level.

PMID- 23113242
TI  - Dynamics of heart rate parameters in students with various personal anxiety
      levels during computerized testing.
AB  - Students with low level of initial (pre-test) personal anxiety demonstrated a
      high level of modulating effects on the heart rate in all basic frequency ranges
      (VLF, LF, and HF) resulting in a greater total power of heart rate variability
      spectrum compared to students with high personal anxiety. The peculiarities of
      dynamics of heart rate variability were revealed during a real learning task,
      which correlated with personal anxiety level. In comparison with highly anxious
      students, the low-anxious group demonstrated more pronounced drop in the power of
      all ranges of the heart rate variability spectrum during testing followed by
      restoration of these power indices to initial levels after completion of the
      test. In contrast, the drop of the total power of the heart rate variability
      spectrum and in the power of its individual components persisted in students with
      high anxiety level even after the end of the testing.

PMID- 23113243
TI  - Nociceptive sensitivity and lymphocytic index of peripheral blood in rats with
      different behavioral activity in model of inflammatory pain provoked by injection
      of freund's complete adjuvant and bovine serum albumin.
AB  - Nociceptive thresholds decreased in rats at the early stage of inflammatory
      reaction induced by subcutaneous injection of BSA and complete Freund's adjuvant.
      At the later stage of this reaction, there was a trend of restoring nociceptive
      parameters in behaviorally passive rats in contrast to active animals, which
      demonstrated further decrease in the nociceptive thresholds. During the late
      inflammatory period, the lymphocytic index (by Shaganin) changed unidirectionally
      in the rats with different behavioral parameters. Probably, the changes in
      nociceptive thresholds were not triggered by the shift in lymphocyte/segmented
      neutrophil ratio, but resulted from production of yet not established
      biologically active agents with proalgesic and analgesic nature.

PMID- 23113244
TI  - Peculiarities of heart rhythm variability in narcotized and immobilized wakeful
      rats during blockade of calcium channels.
AB  - In narcotized rats, verapamil and cinnarizine modified some heart rate
      variability (HRV) indices and heart rate (HR) indicating up-regulation of
      parasympathetic tone in contrast to nifedipine that elevated activity of
      sympathetic subdivision of ANS producing no influence on HR. In wakeful stressed
      rats, the time-domain and geometric analysis established that verapamil decreased
      HR and up-regulated sympathetic tone; nifedipine elevated sympathetic tone and
      produced no effect on HR, while cinnarizine enhanced parasympathetic tone without
      any effect on HR. Spectrum analysis of HRV revealed probable activation of some
      other neurohumoral mechanisms by the employed calcium blockers.

PMID- 23113245
TI  - Mechanisms of the anti-inflammatory and antifibrotic activity of a sympatholytic
      agent during toxic pulmonary fibrosis.
AB  - The effect of a course treatment with a sympatholytic reserpine on the
      inflammatory response and connective tissue proliferation in the lungs of C57Bl/6
      mice was studied on the model of toxic pulmonary fibrosis induced by
      intratracheal administration of bleomycin. This sympatholytic reduced
      infiltration of the alveolar interstitium and alveolar ducts with inflammatory
      cells (lymphocytes, macrophages, neutrophils, and plasma cells) and prevented
      connective tissue proliferation in the lungs. The anti-inflammatory effect of
      reserpine was associated with a decrease in activity of bone marrow granulocyte
      erythroid-macrophage-megakaryocyte and granulocyte precursors (proliferation and
      mobilization). The antifibrotic effect of reserpine was due to a decrease in the
      number of committed precursors for mesenchymopoiesis.

PMID- 23113246
TI  - Effect of uridine on energy metabolism, LPO, and antioxidant system in the
      myocardium under conditions of acute coronary insufficiency.
AB  - Experiments on rats have shown that preventive treatment with uridine stabilizes
      energy metabolism in the heart under conditions of 60-min left coronary artery
      occlusion. The preparation also prevented antioxidant system dysfunction and LPO
      hyperactivation. 5-Hydroxydecanoate, a selective blocker of mitochondrial ATP
      dependent K(+)-channels, abolished the protective effect of uridine, which
      attested to the involvement of these channels into mechanisms of the
      cardioprotective effect of the preparation. The elimination of intravenously
      administered uridine from the blood of animals with acute ischemia was
      accelerated in comparison with that in intact animals, which could suggest the
      participation of this nucleoside in the processes of activation of intracellular
      anti-ischemic defense mechanisms.

PMID- 23113247
TI  - Effect of oxidized dextran on reparative regeneration of the skin after burn
      injury.
AB  - In adult Wistar rats, a 3B degree skin burn was modeled and treated by daily
      application of 5% aqueous solution of oxidized dextran (molecular weight of 60
      kDa) on the wound surface. In animals treated with oxidized dextran, neutrophil
      count in the connective tissue adjacent to the wound increased by day 5 and then
      decreased by day 21 after burn infliction; proliferation of fibroblasts was
      observed later than in untreated animals, in whom inflammation run a subacute
      course. Oxidized dextran increased the content of macrophages in the wound and
      surrounding connective tissue from days 14 to 21 after burn infliction and
      promoted effective and complete healing of the skin defect. Regeneration was
      realized mainly due to proliferation of keratinocytes at the wound edges and was
      completed by 7 days earlier than in untreated animals, in whom the area of injury
      by day 21 decreased by only 2 times (vs. 10 times in treated rats).

PMID- 23113248
TI  - Arginine-containing tripeptide Pro-Arg-Gly is involved in the regulation of the
      function of anticoagulation and insular systems under persistent hyperglycemia.
AB  - Intranasal administration of regulatory peptide PRG to rats against the
      background of persistent hyperglycemia improves blood antiplatelet and
      anticoagulant-fibrinolytic potential and normalizes blood sugar in comparison
      with the corresponding parameters in control animals that did not receive the
      peptide. The fibrinolytic and antiplatelet activities of blood plasma remained
      elevated 6 days after peptide withdrawal against the background of unchanged
      glucose administration.

PMID- 23113249
TI  - Role of metabotropic glutamate receptors in the mechanisms of experimental
      parkinsonism development.
AB  - We studied the effects of metabotropic glutamate receptor 5 (mGluR5) antagonist 6
      methyl-2-(phenylethynyl)-pyridine (MPEP) on the development of catalepsy and NO
      generation in the striatum of rats under conditions of long-term treatment with
      low doses of rotenone, a mitochondrial complex I inhibitor. In rats receiving
      single intraperitoneal injection of rotenone (1.5 mg/kg), NO concentration in the
      striatum did not differ from that in animals receiving sunflower oil. No signs of
      catalepsy were observed at these terms in both animal groups. It was demonstrated
      that long-term rotenone treatment induced catalepsy associated with enhanced NO
      production in the rat striatum. mGluR5 antagonist MPEP alleviated catalepsy
      caused by long-term rotenone treatment and prevented rotenone-induced stimulation
      of NO generation.

PMID- 23113250
TI  - Contribution of the complement system to realization of biological fluid
      cytotoxicity in health and disease.
AB  - The cytotoxic effects of human blood serum were studied under normal and
      pathological conditions. The contribution of the complement system to the
      realization of this effect was demonstrated. Significant differences in the serum
      capacity to kill foreign cells were detected for healthy subjects and asthmatics.
      Bovine sperm suspension can serve as the test object for rapid evaluation of
      functional activity of the complement system.

PMID- 23113251
TI  - Antistress effect of Semax in the course of recovery of spleen lymphoid
      structures after the stress in rats with different behavioral activity.
AB  - We studied the effect of antistress peptide Semax, an ACTH4-10 analogue, on the
      cellular composition of spleen lymphoid structures in Wistar rats with different
      stress tolerance in the course of post-stress recovery (days 1, 3, 14, and 30).
      Preliminary administration of Semax alleviates stress-induced proliferation of
      macrophages and destructive processes in functionally active zones of the rat
      spleen on days 1, 3, and 14 after the stress exposure, which attests to its
      capacity to reduce the adverse effects of 1-h stress load on proliferation of
      macrophages and destructive processes in functionally active zones of this organ.

PMID- 23113252
TI  - Involvement of HLDF protein and anti-HLDF antibodies in the mechanisms of blood
      pressure regulation in healthy individuals and patients with stable hypertension
      and hypertensive crisis.
AB  - We studied the relationships between the blood serum levels of human leukemia
      differentiation factor HLDF, idiotypic and anti-idiotypic antibodies to HLDF, and
      clinical indicators of cardiovascular function in apparently healthy individuals
      and patients with essential hypertension and cerebral hypertensive crisis.
      Markedly reduced HLDF levels and anti-HLDF antibody titers were found in the
      blood of the examined patients. Correlations between HLDF levels, duration of
      hypertension, and systolic and diastolic BP were revealed. These findings suggest
      that the studied molecular factors are involved in the mechanisms of BP
      regulation under normal conditions and during hypertension development. The
      protein HLDF and anti-HLDF antibodies can be considered as biomarkers for early
      diagnosis of hypertension and its cerebral complications.

PMID- 23113253
TI  - Modification of normal activities of angiotensin II and angiotensin IV in rats
      with experimental hypo- and hyperglycemia.
AB  - Changes in blood glucose levels are paralleled by modification of normal
      activities of angiotensin II and angiotensin IV. Hypo- and hyperglycemia
      similarly reduced the hypertensive effect of angiotensin II and similarly
      distorted the initial hypotensive effect of angiotensin IV. Presumably, the
      adaptation and compensatory processes in the renin-angiotensin system under
      conditions of shifted homeostatic constants manifest by phenomena of external
      reintegration and redistribution of functions of its individual peptide
      components. This provides restructuring of the mechanisms of intra- and
      intersystemic organization of physiological functions under extreme conditions.

PMID- 23113254
TI  - Effect of infrared and X-ray radiation on thymus cells and the rate of growth of
      Ehrlich carcinoma.
AB  - We studied the effect of infrared light with a wavelength of 850 nm and modulated
      frequency of 101 Hz and X-ray radiation on the induction of cross-adaptive and
      radiation responses in the thymus and on the rate of tumor growth in mice in
      vivo. Preliminary exposure to infrared and X-ray radiation was shown to result in
      recovery in thymus weight after irradiation in a dose of 1.5 Gy and also
      inhibited the growth rate of Ehrlich carcinoma. These data attest to common
      mechanisms of the adaptive response induced by infrared and X-ray radiation in
      mice. Infrared light can be used as an adaptogen to adapt the animals to adverse
      factors.

PMID- 23113255
TI  - Changes in activity of proline-specific peptidases in rat model for dementia of
      Alzheimer's type.
AB  - We studied the role of proline-specific peptidases in the pathogenesis of
      Alzheimer's disease. Testing of conditioned passive avoidance 24 h after learning
      showed that chronic administration of scopolamine to rats 4-fold reduced the
      latency of entry into the dark chamber in comparison with controls (intact
      animals). Activity of prolyl endopeptidase was significantly higher than in the
      controls in both the cortex and hippocampus. Changes in dipeptidyl peptidase IV
      activity were observed only in the cortex. Injection of AF-64A toxin into Meynert
      nucleus basalis reduced the latency of entry into the dark compartment by 75% in
      comparison with that in sham-operated and intact controls. Prolyl endopeptidase
      activity was reduced in the frontal cortex and hippocampus, but not in
      hypothalamus. Changes in dipeptidyl peptidase IV activity were detected only in
      the frontal cortex.

PMID- 23113257
TI  - Antioxidant protection of the brain in rats during acute stress and
      administration of interleukin-1beta.
AB  - We studied the effect of IL-1beta on antioxidant enzyme activity in emotiogenic
      structures of the brain (hypothalamus, sensorimotor cortex, and amygdala) in
      behaviorally passive and active rats with different sensitivity to stress. One
      hour immobilization of animals with simultaneous electrocutaneous stimulation was
      used as a model of stress. An intraperitoneal injection of IL-1beta (5 MUg/kg)
      was followed by the decrease in glutathione reductase activity in the
      hypothalamus of rats. Behaviorally active animals of the IL-1beta group were
      characterized by an increase in the activities of Cu/Zn superoxide dismutase and
      glutathione peroxidase in the sensorimotor cortex and amygdala, respectively. IL
      1beta administration was accompanied by activation of Cu/Zn superoxide dismutase
      and glutathione peroxidase in the amygdala of passive rats. Pretreatment with IL
      1beta abolished the poststress changes in enzyme activity in the hypothalamus and
      sensorimotor cortex of active and passive rats, respectively. These data
      illustrate the specific effects of IL-1beta on antioxidant protection of CNS
      tissues in rats with various behavioral characteristics.

PMID- 23113256
TI  - Specific features of biogenic amine content in the cerebral cortex during
      experimental intracerebral hemorrhage in rats with various behavioral
      characteristics.
AB  - Experiments on Wistar rats showed that modeling of hemorrhage in the left caudate
      nucleus of the brain in behaviorally passive specimens is mainly accompanied by
      an increase in biogenic amine content in the sensorimotor cortex of the right
      cerebral hemisphere (particularly on day 3 after the surgery). Norepinephrine
      content in the sensorimotor cortex of the right cerebral hemisphere in
      behaviorally active rats was reduced over 7 days after the development of
      intracerebral hemorrhage. The contents of dopamine and serotonin in brain tissue
      of behaviorally active animals most significantly increased on day 7 after
      experimental stroke. Our results indicate that experimental hemorrhage in the
      left caudate nucleus of rats with various behavioral characteristics is
      accompanied by specific changes in biogenic amine content in the sensorimotor
      cortex of the right cerebral hemisphere. We conclude that neurochemical processes
      in brain structures distant from the site of hemorrhage play an important role in
      the pathogenesis of hemorrhagic stroke.

PMID- 23113258
TI  - Potentiation of hemostimulating effects of erythropoietin with pegylated
      hyaluronate-endo-beta-N-acetylhexosaminidase.
AB  - Pegylated hyaluronate-endo-beta-N-acetylhexosaminidase considerably potentiates
      the hemostimulating effects of erythropoietin due to intensification of
      proliferation and differentiation of erythroid precursors against the background
      of enhanced secretion of hemopoietins by nonadherent hemopoiesis-inducing
      environment cells and elevation of serum erythropoietin concentration. The use of
      the enzyme allows 10-fold reduction of the maximum effective erythropoietin dose.

PMID- 23113259
TI  - Effect of combined administration of afobazole and 5-HT2b/2c receptor antagonist
      SB-200646A on neurochemical profile of brain structures in C57Bl/6 and BALB/c
      mice.
AB  - The effects of combined administration of afobazole and 5-HT(2b/2c)receptor
      antagonist SB-200646A on the content of monoamines and their metabolites in brain
      structures of C57Bl/6 and BALB/c mice were studied by the methods of HPLC with
      electrochemical detection. Combined administration of afobazole and SB-200646A
      increased the content of epinephrine in the striatum of BALB/c mice (to 230% of
      the control) and in the hippocampus of both mouse strains. The content of
      dihydroxyphenylacetic and homovanillic acids and parameters of dopamine
      metabolism in these structures were reduced. The content of dopamine in the
      hypothalamus and amygdala was elevated in C57Bl/6, but not in BALB/c mice. These
      findings attest to the involvement of monoamine systems of the brain in the
      mechanism of afobazole action and suggest that the enhanced anxiolytic effect of
      afobazole combination with SB-200646A can be interpreted as a positive modulation
      of the effect of anxiolytic determined by blockade of 5-HT(2)serotonin receptors.

PMID- 23113260
TI  - Effects of neurotensin dipeptide analog dilept on dopamine metabolism and
      synthesis in the nucleus accumbens of Wistar rats.
AB  - We studied the effects of neurotensin dipeptide analog Dilept (N-caproyl-L-prolyl
      L-tyrosine methyl ester) on dopamine metabolism and synthesis in the nucleus
      accumbens of Wistar rats. Dilept increased the levels of dopamine and its
      metabolites (homovanillic acid and dioxyphenylalanine) and stimulated dopamine
      turnover in this structure. Dilept accelerated dopamine synthesis under
      conditions of pulsed activity blockade in dopaminergic neuron by injection of
      gamma-butyrolactone combined with inhibition of aromatic acid decarboxylase with
      3-hydroxybenzylhydrazine. The spectrum of pharmacological activities of Dilept
      towards the dopaminergic system of the nucleus accumbens was similar to that of
      atypical neuroleptics and neurotensin (endogenous antipsychotic).

PMID- 23113261
TI  - In vitro effects of sporobacterin probiotic on the function of donor granulocyte
      macrophage cells.
AB  - The effects of sporobacterin probiotic (Bakoren Company) on oxidative activity of
      donor granulocyte-macrophage cells (GMC) were studied in vitro by luminol
      dependent chemiluminescent method, and the effects of the probiotic on the
      production of pro- and anti-inflammatory cytokines were evaluated by ELISA. The
      probiotic dose-dependently stimulated spontaneous production of free radicals by
      GMC; combined treatment with immunomodulators likopid, polyoxydonium, and IFN
      alpha2a produced a more potent effect. Sporobacterin stimulated the production of
      pro- and anti-inflammatory cytokines in cell cultures. These data confirmed the
      immunomodulatory effect of sporobacterin, an important component in the
      phagocytic system cells.

PMID- 23113262
TI  - Role of nicotinic and muscarinic cholinoreceptors in the realization of the
      cholinergic anti-inflammatory pathway during the early phase of sepsis.
AB  - Stimulation of nicotinic and muscarinic cholinoreceptors (nAChR, mAChR) in
      outbred albino mice with nicotine and aceclidine, respectively, in single
      equilethal doses 0.5 DL(50)6 h before sepsis induction significantly reduced
      animal mortality due to a decrease in blood concentrations of proinflammatory
      cytokines IL-1beta, IL-6, and MIP-2. Stimulation of mAChR (injection of
      aceclidine) stimulated the neutrophilic phagocytic and metabolic activity.
      Realization of the cholinergic anti-inflammatory pathway (stimulation of the
      peripheral nicotinic cholinoreceptors (alpha7nAChR) and central muscarinic
      cholinoreceptors (mAChR) was modulated by stimulation of the muscarinic
      cholinoreceptors of the phagocytic monocytic system cells.

PMID- 23113263
TI  - Effects of tenoten on anxiety and depression disorders in patients with epilepsy.
AB  - The efficiency and safety of tenoten for anxiety and depression disorders in
      epileptics has been demonstrated. The drug does not change the incidence and
      severity of epileptic episodes, does not deteriorate the course of the underlying
      disease, and can be well combined with anticonvulsants. The results indicate the
      efficiency of tenoten used to arrest the anxio-depressive disorders in epilepsy.

PMID- 23113264
TI  - Excretion of compound M-11 and its metabolites with urine and feces in rats.
AB  - The excretion of compound M-11 and its metabolites with the urine and feces was
      studied in rats after intraperitoneal and oral administration in a dose of 25
      mg/kg. Experiments showed that 1% metabolites were detected in excretions over 24
      h irrespective of the route of administration, while the initial compound was not
      found even in trace amounts.

PMID- 23113265
TI  - Functional aspects of neuroprotective effects of new salts and compositions of
      baclofen in the convulsive syndrome caused by electroshock.
AB  - New salts of baclofen (4-amino-3-(para-chlorophenyl)-butyric acid) and its
      compositions with organic carbonic acids (citric, succinic, malic, oxalic,
      nicotinic, glutamic acids and glycine) exhibited neuroprotective and
      anticonvulsive effects. They reduced the intensity of the convulsive syndrome and
      postconvulsive psychoneurological disorders in animals exposed to the maximum
      electroshock and electroconvulsive shock. Analogs of baclofen containing citrate
      and to a lesser extent those containing glutamate and glycine were significantly
      more active than the initial substance.

PMID- 23113266
TI  - Glutamate receptor modulator dimebon stimulates consolidation and reconsolidation
      of weak memory in chicks.
AB  - Effects of glutamate receptor modulator dimebon on memory consolidation and
      reconsolidation were investigated in passive avoidance paradigm in newborn
      chicks. Systemic administration of 0.1 mg/kg dimebon 5 min before or 4 h after
      "weak" training resulted in formation of long-term memory. Dimebon administration
      in combination with memory reactivation 24 h after "weak" training recovered the
      memory decayed by the time of reminder and ensured its subsequent long-term
      maintenance over 24 h. Thus, we showed the possibility for dimebon-induced
      recovery of the memory that decayed and had no manifestations in behavior.
      Dimebon administration potentiated early and late stages of memory consolidation
      in learning as well as in memory reconsolidation following its reactivation.

PMID- 23113267
TI  - Loperamide effects on anxiety level and feeding behavior in rats. Role of vagal
      afferentation.
AB  - We investigated the role of vagal afferentation in the interaction of the
      peripheral and central parts of the endogenous opioid system, in the mechanisms
      of sensorial satiation and anxiety in rats. It has been established that
      vagotomized rats spent less time in open arm of the plus-maze in comparison with
      sham-operated animals. Peripheral administration of MU-opioid receptor agonist
      loperamide was shown to reduce anxiety level in sham-operated rats and had no
      effect on this parameter in vagotomized animals. Testing in a PhenoMaster module
      system showed that loperamide administration suppressed feeding behavior in sham
      operated animals and partially suppressed it in vagotomized animals. Vagotomy
      virtually completely blocked the anxiolytic effect of loperamide and partially
      blocked the anorexigenic effect of the MU-opioid receptor agonist.

PMID- 23113268
TI  - Effects of peripheral MU, delta, and Kappa-opioid receptor agonists on the levels
      of anxiety and motor activity of rats.
AB  - The effects of intragastric administration of MU-, delta, and Kappa-opioid
      receptor agonists DAMGO, DADLE, and ICI 204,448, respectively, on the anxiety and
      motor activity of rats in an elevated plus-maze were studied. Peripheral
      administration of ICI 204,448 produced an anxiolytic effect, but had no effect on
      motor activity of rats. DAMGO and DADLE reduced motor activity; DADLE also
      increased anxiety. The data on the opposite effects of ICI 204,448 and DADLE on
      anxiety confirmed our previous hypothesis on the interactions between the central
      and peripheral components of the endogenous opioid system.

PMID- 23113269
TI  - Proliferative response of lymphocyte to pokeweed mitogen depends on the
      concentration of endogenous cortisol in the early post-traumatic period in
      patients with penetrating eye injury.
AB  - The intensity of lymphocyte proliferation in response to pokeweed mitogen depends
      on cortisol level in the peripheral blood in the early post-traumatic period of
      penetrating eye injury. Lymphocyte proliferation in 72- and 96-h cultures from
      patients with high levels of endogenous hormone was suppressed. In 120-h
      cultures, the intensity of proliferation remains unchanged. Lymphocyte blast
      transformation was increased in 120-h cultures from patients with normal cortisol
      concentration and remained unchanged in case of low cortisol level.

PMID- 23113270
TI  - Optimal detection of serum antipaternal antileukocytic antibodies after injection
      of allogenic lymphocytes in women with habitual abortions.
AB  - The level of antipaternal antileukocytic antibodies detected by flow cytometry is
      a parameter reflecting the efficiency of alloimmunization of women with
      reproductive disorders during preparation to pregnancy. The results of evaluation
      of antipaternal antileukocytic antibodies by two modifications of the method are
      presented. The optimal method for detection of antipaternal antileukocytic
      antibodies after immunocytotherapy is selected.

PMID- 23113271
TI  - Nociceptive thresholds of the response to lipopolysaccharide injection into the
      limbic structures of the brain in rats.
AB  - Microinjections of LPS into the limbic structures of rat brain (dorsal
      hippocampus and caudal compartment of the cingulate fascicle) caused opposite
      effects on the nociceptive thresholds: injection into the dorsal hippocampus
      enhanced perception and reduced the emotional affective perception of pain, while
      injection into the cingulate fascicle reduced the perceptual and enhanced the
      emotional components of the nociceptive reaction. These results indicated
      specific involvement of these limbic structures in nociception modulation during
      induction of the immune response in CNS.

PMID- 23113272
TI  - Specific changes in c-fos expression and colocalization with DNA in identified
      neuronal nuclei of edible snail following neurotransmitter application.
AB  - The effects of serotonin and glutamate on c-fos expression and c-Fos
      colocalization with DNA were immunohistochemically studied in defense behavior
      command neurons R-LPa2-3 in snail Helix lucorum. Simultaneous neurotransmitter
      application resulted in increased c-Fos-immunoreactivity and colocalization with
      DNA-specific stain Hoechst 33342 in LPa2 and RPa2 neurons with specific dynamics
      for each identified cell. In the nuclei of LPa3 and RPa3 neurons,
      neurotransmitter application did not significant change the c-Fos level. These
      findings are indicative of specific spatiotemporal changes in c-fos expression
      and c-Fos colocalization with DNA in investigated neurons of edible snail under
      the influence of neurotransmitters.

PMID- 23113273
TI  - Recovery of impaired memory and c-fos gene expression in brains of amnestic
      animals in response to reminder stimulation.
AB  - Possible mechanisms of recovery of the memory impaired during consolidation
      process were investigated. In mice, amnesia was induced by intraperitoneal
      cycloheximide (100 mg/kg) administration 20 min before exposure to tone signal
      combined with footshock (2 sec, 0.5 mA). Reminder by the footshock (2 sec, 0.5
      mA) 24 h after the learning procedure resulted in recovery of impaired memory in
      amnestic animals up to the level of control animals. Analysis of c-Fos expression
      in response to reminder indicated increased number of c-Fos-positive cells in
      prelimbic cortex in the animals with unaffected memory in comparison with
      corresponding parameter in amnestic animals. These findings are indicative of
      impairment in prelimbic cortex activity in experimental amnesia as well as for
      reminder ability to recover the memory impaired in that way.

PMID- 23113274
TI  - Effects of systemic administration of histone deacetylase inhibitor on memory
      formation and immediate early gene expression in chick brain.
AB  - We studied the effects of histone deacetylase inhibitor that stimulates
      transcriptional activity via histone hyperacetylation on memory formation. Sodium
      butyrate and sodium valproate enhanced memory in chicks following "weak" training
      with memory transfer into long-term state. Quantitative analysis of c-Fos and
      ZENK transcriptional factor gene expression in six structures of chick brain
      revealed induction of these genes in the structures involved in this type of
      learning. Sodium valproate administration did not increase this induction, but
      even reduced it. These findings suggest that sodium butyrate and sodium valproate
      exert cognitive stimulating action in the "weak" memory formation paradigm, and
      that this effect is not mediated via enhanced expression of transcriptional
      factors, which are traditionally considered as "molecular switcher" for memory
      transfer into long-term state.

PMID- 23113275
TI  - Regional features of the expression of genes involved in neurogenesis and
      apoptosis in the brain of adult rats.
AB  - The expression of mRNA of genes involved in neurogenesis and apoptosis (Apaf1,
      Ascl1, Bax, Bcl2, Casp3, Casp8, Casp9, Dffb, Myh10, Naip2, Napa, Notch2, Numb,
      Pura, S100a6, Tnf) in the prefrontal cortex, hippocampus, and cerebellum was
      studied in adult rats. The content of mRNA of these genes (except Apaf1) was
      several-fold higher in the cerebellum than in the hippocampus and brain cortex.
      In the hippocampus, the expression of Apaf1 was significantly lower than in the
      prefrontal cortex, while the expression of Ascl1, Pura, S100b, and Tnf was
      higher. Regional differences in the direction, strength, and numbers of
      significant correlations between the expression of the studied genes were
      detected. Documented differences in gene expression were regarded as validation
      of the structural and functional cooperation of neurogenesis and apoptosis at the
      molecular genetic level.

PMID- 23113276
TI  - Repeated moderate stress stimulates the production of dehydroepiandrosterone
      sulfate (DHEAS) and reduces corticosteroid imbalance in old Macaca Mulatta.
AB  - Young (6-8 years) and old (21-30 years) Macaca mulatta females were subjected to
      gentle immobilization (2 h daily at 15.00) for 10 days. Blood specimens were
      collected before the exposure and 15, 30, 60, 120, 240 min and 24 h after the
      beginning of exposure on days 1, 3, and 10. The adrenocortical reaction to stress
      was maximum on day 1 in all animals. The increase of cortisol (F) and
      dehydroepiandrosterone sulfate (DHEAS) concentrations in young monkeys decreased
      on days 3 and 10, DHEAS drop being less pronounced in comparison with F, as a
      result of which F/DHEAS molar concentration ratio changed negligibly. In old
      monkeys the basal DHEAS levels were lower, while the F/DHEAS ratio was higher
      than in young animals. Repeated immobilizations inhibited F elevation on day 3,
      caused no changes in DHEAS reaction, led to increase of basal DHEAS levels and to
      a reduction of F/DHEAS ratio on days 2, 3, 4, 10, 11. Hence, chronic moderate
      stress stimulated the production of DHEAS and reduced the corticosteroid
      imbalance in old monkeys.

PMID- 23113277
TI  - Effect of intravenous low-intensity laser irradiation of the blood on clinical
      and laboratory parameters of hepatocellular insufficiency.
AB  - Patients with hepatocellular insufficiency received a course of intravenous laser
      irradiation of the blood. After the treatment, a positive dynamics of clinical
      and biochemical indices of the major hepatic syndromes was observed: alleviation
      of the major clinical symptoms and significant positive changes in biochemical
      parameters (AST, ALT, bilirubin, alkaline phosphatase, lactate dehydrogenase, and
      total cholesterol).

PMID- 23113278
TI  - Increased beta-endorphin level in blood plasma as an indicator of positive
      response to depression treatment.
AB  - Preliminary data indicate that increased blood plasma level of beta-endorphin in
      patients with nonpsychotic unipolar depression after 2 weeks of treatment
      correlates with the positive response to therapy. This parameter can be regarded
      as an objective indicator of potential improvements. Further studies aimed at
      determining the value of blood beta-endorphin levels in patients with mood
      disorders for the diagnostics and estimating the therapeutic success in this
      disease are required.

PMID- 23113279
TI  - Maternal deprivation in early ontogeny impairs olfactory learning with mother's
      grooming imitation in 129Sv mice.
AB  - Early experience, mediated by mother's care, exerts long-term effects on the
      formation of behavioral phenotype. However, there are no published data on the
      effects of such experience on the results of early learning. We investigated the
      effects of maternal deprivation associated with handling in 129Sv mice during
      postnatal days 3-6 on the results of olfactory learning with mother's grooming
      imitation used as the reinforcement on postnatal day 8. Mother deprivation and
      handling procedure are shown to impair early olfactory learning.

PMID- 23113280
TI  - Neurogenesis enhancer RO 25-6981 facilitates repeated spatial learning in adult
      rats.
AB  - The effects of Ro 25-6981 (selective NMDA receptor blocker) in a dose stimulating
      neurogenesis on repeated learning, reversal learning, and memory reconsolidation
      were studied in adult rats in Morris water maze. Ro 25-6981 facilitated repeated
      learning 13 days after injection, but did not influence reversal learning. The
      blocker injected directly before reminder did not disturb repeated learning and
      reversal learning in Morris water maze. These effects of Ro 25-6981 on the
      dynamics of repeated learning seemed to be due to its effects on neurogenesis
      processes in adult brain.

PMID- 23113281
TI  - 5-Bromo-2'-deoxyuridine impairs long-term food aversion memory in edible snail.
AB  - We studied the involvement of DNA synthesis into molecular mechanisms of long
      term memory. Nucleoside analogue 5-bromo-2'-deoxyuridine (BrdU) is known to
      incorporate into synthesizing DNA and prevent subsequent DNA replication from
      this region. To investigate the effect of BrdU administration on long-term
      memory, terrestrial gastropods edible snails Helix lucorum were trained in the
      food aversion paradigm. Single-session training (carrot presentation combined
      with application of 10% quinine solution, three carrot presentations with 10-min
      intervals) resulted in the formation of long-term memory that persisted for at
      least 45 degrees  days. BrdU administration (250 mg/kg) 30 min before training
      impaired long-term memory tested 24 h later. Immunohistochemical study revealed
      BrdU incorporation in the nuclei of identified neurons of defensive behavior.

PMID- 23113282
TI  - Cardiac natriuretic peptides and development of hereditary hypertension in rats.
AB  - Ultrastructure of the right atrial cardiomyocytes of suckling ISIAH rats was
      studied to clarify the role of cardiac natriuretic peptides in hypertension
      development during the period when blood pressure is not yet elevated.
      Cardiomyocytes diameter was significantly greater, Golgi complex was more
      developed, and granules in the sarcoplasm were more abundant in ISIAH rats as
      soon as on postnatal day 12 in comparison with age-matched normotensive animals.
      The smaller diameter of granules and their qualitative composition (ratio of
      forming, mature, and dissolving forms) attest to active synthesis and release of
      secretory product. In 21-day-old ISIAH rats, granule size and qualitative
      composition reflected increased accumulation of hormones in the cells. Thus,
      morphological features of increased production of natriuretic peptides in the
      right atrial myocytes were revealed in rats during the first postnatal month
      before manifestation of hereditary hypertension.

PMID- 23113283
TI  - Comparative morphology of laser lesion sites in parenchymal organs (liver,
      kidney, spleen).
AB  - The inflammatory and reparative processes in the parenchymal wounds after laser
      coagulation are characterized by predominance of proliferative reaction. Injury
      foci are always spatially separated from the intact tissue. Coagulation necrosis
      and thrombosis lead to suppression of the exudative component of inflammation in
      sites of laser exposures in the liver, kidneys, and spleen. Early macrophage
      response stimulates proliferation of fibroblasts and formation of the fine
      connective tissue scar within 14 days.

PMID- 23113284
TI  - Remodeling of the muscle layer (detrusor muscle) of hyperactive bladder disease
      in patients with benign prostatic hyperplasia.
AB  - We studied remodeling of the detrusor of hyperactive bladder in patients with
      benign prostatic hyperplasia. Detrusor remodeling was caused by degenerative and
      atrophic changes and elimination of smooth muscle cells, compensatory hypertrophy
      of remaining cells, and diffuse or focal-diffuse replacement fibrosis. Focal or
      diffuse infiltration of all layers of the detrusor with lymphocytes and plasma
      cells is an important pathologic feature of hyperactive bladder. These changes
      correlated with pronounced remodeling of the glandular and fibrotic-muscular
      layers in the prostate gland. We have identified stereotyped patterns of the
      intracellular reorganization of smooth muscle cells in the detrusor of
      hyperactive bladder and in the prostate with benign prostatic hyperplasia, which
      represent both the compensatory and adaptive reactions (hypertrophied cells with
      minor ultrastructural changes) and the types of smooth muscle cell injury ("dark"
      electron-dense cells and "light" cells with pronounced lysis of myofilaments and
      discomplexation of organelles).

PMID- 23113285
TI  - Effect of gonadectomy on activity of neuronal 3beta-hydroxysteroid dehydrogenase
      in some brain structures.
AB  - 3beta-Hydroxysteroid dehydrogenase is a key enzyme in the synthesis of steroid
      hormones in steroid-producing organs, including the brain producing
      neurosteroids. 3beta-Hydroxysteroid dehydrogenase activity can be a marker of
      steroid-producing cells. We present the results of histochemical assay of this
      enzyme in the neocortex, hippocampus, and cerebellar cortex of gonadectomized
      prepubertal rats. The positive reaction was detected in hippocampal neurons,
      ganglionic layer cells of the cerebellar cortex (Purkinje cells), and solitary
      neocortical neurons of male and female rats. Gonadectomy significantly increased
      enzyme activity in neocortical (layer V) and hippocampal neurons and had no
      effect on the intensity of the reaction in Purkinje cells.

PMID- 23113286
TI  - Structural and functional features of lipid-containing hepatocytes in hepatitis
      C.
AB  - Pathomorphological studies of lipid-containing hepatocytes included in the system
      of major markers of hepatitis C showed that the phase of hepatitis C virus
      replication (PCR data) corresponds to subplasmalemmal microvesicular steatosis of
      hepatocytes.

PMID- 23113287
TI  - Morphological features of the lymphoepithelial structures of the jejunum after
      the stress in rats.
AB  - We studied the effect of acute emotional stress on functional status of lymphoid
      epithelial structures of the jejunum in rats with different behavioral activity.
      Morphological and functional characteristics of lymphoid tissue were assessed
      using morphometric, histological and electron microscopic methods. In
      behaviorally active and passive rats, reduction in villus height, area of the
      epithelium and lymphoid tissue of the jejunum was recorded on the third day after
      acute emotional impact. At that, the largest number of destructively modified
      lymphoid cells was identified by comparison with the other time points. Moreover,
      destruction of the apical part of the jejunal villi was observed on days 3 and 7
      after stress exposure. Recovery of the lymphoepithelial structures of the jejunum
      after acute stress exposure was detected on day 14.

PMID- 23113288
TI  - A method of creation a cell monolayer based on organotypic culture for screening
      of physiologically active substances.
AB  - We developed a method of culturing and phenotyping of a monolayer of cells of the
      retinal tissue, thymus and spleen on the basis of organotypic culture. All
      characteristic types of neurons and fibroblasts were found in their
      microenvironment in the retinal cell monolayer. Lymphocytes, macrophages, and
      fibroblasts were verified in the monolayer of thymus and spleen cells.
      Histological staining, immunocytochemistry, and electron microscopy demonstrated
      the possibility of assessing the differentiation degree and functional activity
      of the cell monolayer. The developed technique preserves cell-cell interactions
      and a variety of cell types characteristic of the examined organ in the
      monolayer. This opens up new prospects for its application in basic research and
      in screening of different physiologically active substances.

PMID- 23113289
TI  - Mathematical modeling of atrial fibrillation.
AB  - Electrical activity of the heart during ventricular fibrillation was modeled as a
      sum of N independent pulse streams with various amplitude-frequency and phase
      characteristics. The data of computational experiments were compared with the
      results of actual physiological experiments on dogs. Identification of the model
      was performed using the least square method. The proposed technique provides the
      computer simulation for studies of the internal structure of irregularities of
      atrial fibrillation.

PMID- 23113290
TI  - Ultrasonic vocalization of rats in various motivational and emotional states.
AB  - We studied the specific features of ultrasonic vocalization of Wistar rats in
      various motivational and emotional states. No significant changes were found in
      ultrasonic vocalization of rats during experimental food motivation and after the
      satisfaction of food requirements. The state of thirst and satisfaction of water
      requirements in animals were associated with an increase in the mean frequency of
      ultrasound and dominance of ultrasonic waves of a higher frequency. The formation
      of a negative emotional state in rats after immobilization with simultaneous
      electrocutaneous stimulation was accompanied by a decrease in the total duration
      of ultrasonic vocalization and shift in the power spectrum of ultrasound towards
      the dominant frequencies of 20-30, 40-50, and 80-90 kHz. During the post-stress
      period, the maximum power of ultrasonic waves approached the baseline (30-40
      kHz). Our results indicate that the formation of various motivational and
      emotional states in rats is characterized by specific patterns of ultrasonic
      vocalization. Therefore, the parameters of ultrasonic vocalization can serve as
      an objective criteria for the subjective state of a living organism.

PMID- 23113291
TI  - Effects of electrical stimulation of the hunger center in the lateral
      hypothalamus and food reinforcement on impulse activity of the stomach in rabbits
      under conditions of hunger and satiation.
AB  - Stimulation of the lateral hypothalamus in preliminary fed animals in the
      presence of the food is associated with successful food-procuring behavior,
      accompanied by regular generation of high-amplitude slow electrical waves by
      muscles of the lesser curvature, body, and antrum of the stomach, which was
      reflected in the structure of temporal organization of slow electrical activity
      in the form of unimodal distribution of slow wave periods typical of satiation
      state. Despite increased level of food motivation caused by stimulation of the
      lateral hypothalamus, the additional food intake completely abolished the
      inhibitory effects of hunger motivation excitement on slow electrical muscle
      activity in the lesser curvature, body, and antrum of the stomach of satiated
      rabbits. Changes in slow electrical activity of the stomach muscles in rabbits
      deprived of food over 24 h and offered food and associated food-procuring
      behavior during electrical stimulation of the lateral hypothalamus have a two
      phase pattern. Despite food intake during phase I of electrical stimulation, the
      downstream inhibitory effect of hunger motivation excitement on myogenic
      pacemaker of the lesser curvature of stomach abolishes the stimulating effect of
      food reinforcement on slow electrical muscle activity in the lesser curvature,
      body, and antrum of the stomach. During phase II of electrical stimulation, the
      food reinforcement decreases inhibitory effect of hunger motivation excitement on
      myogenic pacemaker of the lesser curvature that paces maximal rhythm of slow
      electrical waves for muscles activity in the lesser curvature, body, and antrum
      of the stomach, which is reflected by unimodal distribution of slow electrical
      wave periods. Our results indicated that the structure of temporal organization
      of slow electrical activity of the stomach muscles reflects convergent
      interactions of food motivation and reinforcement excitations on the dorsal vagal
      complex neurons in medulla oblongata.

PMID- 23113292
TI  - Effects of GSM-Frequency Electromagnetic Radiation on Some Physiological and
      Biochemical Parameters in Rats.
AB  - Single exposure of white outbred rats to electromagnetic radiation with a
      frequency 905 MHz (GSM frequency) for 2 h increased anxiety, reduced locomotor,
      orientation, and exploration activities in females and orientation and
      exploration activities in males. Glucocorticoid levels and antioxidant system
      activity increased in both males and females. In addition to acute effects,
      delayed effects of radiation were observed in both males and females 1 day after
      the exposure. These results demonstrated significant effect of GSM-range
      radiation on the behavior and activity of stress-realizing and stress-limiting
      systems of the body.

PMID- 23113293
TI  - Involvement of basal and calcium-activated protein kinase C in neurotransmitter
      secretion in mouse motor synapses.
AB  - Blocker of presynaptic protein kinase C isoforms, GF109203X, reduced quantal
      content of single and rhythmic evoked end-plate potentials. The increase in
      quantal content of single potentials under the effect of 4- aminopyridine was
      neutralized by 75% under the effect of L-type Ca(2+)-channel blocker nitrendipine
      and completely returned to the control level after protein kinase C inhibition
      with chelerythrine. Neither nitrendipine, nor GF109203X affected the potentiating
      effect of tetraethylammonium on quantal content of end-plate potentials. Thus, we
      discovered basal activity of presynaptic protein kinase C under normal conditions
      that is aimed at the maintenance of quantal content of evoked release. It has
      been concluded that 4-aminipyridine, but not tetraethylammonium, triggers Ca(2+)
      entry into the terminal, which activates protein kinase C and enhanced the evoked
      acetylcholine release.

PMID- 23113294
TI  - Energy deficit as a possible factor for the induction of caspase-dependent
      apoptosis in left ventricular myocardial cells during genetically determined and
      secondary arterial hypertension.
AB  - Activities of caspase-3 and caspase-8 in the left ventricular myocardium of
      Chinchilla rabbits with renovascular arterial hypertension and spontaneously
      hypertensive rats were measured after 10-day administration of a macroergic
      compound phosphocreatine. Treatment with phosphocreatine prevented activation of
      caspase-3, but had no effect on caspase-8 during secondary and genetically
      determined arterial hypertension. Our results indicate that the intrinsic
      mechanism of the induction of the caspase cascade in myocardial cells dominates
      over the extrinsic pathway during both types of arterial hypertension. Energy
      deficit is one of the inducing factors of these processes.

PMID- 23113295
TI  - Effect of opioid peptides on the content of LPO products and antioxidant enzyme
      activity in the liver of rats after restraint stress.
AB  - Administration of opioid peptides dynorphin A (1-13) and DSLET was followed by a
      decrease in the stress-induced activation of LPO and increase in SOD activity in
      the liver tissue of rats. DAGO produced a similar, but less pronounced effect.
      The observed changes can be related to a specific distribution of opioid
      receptors in the liver tissue and stress-limiting influence of these peptides in
      the whole body.

PMID- 23113296
TI  - Effect of locomotor activity on ultrastructure of cerebellar neurons,
      neurological disturbances, and survival of Krushinsky-Molodkina rats with
      hemorrhagic stroke.
AB  - We studied the effect of locomotor activity on the ultrastructure of cerebellar
      neurons, neurological disturbances, and survival rate in Krushinsky-Molodkina
      rats during the development of hemorrhagic induced by acoustic stress. In animals
      with high spontaneous locomotor activity, severe edema of cerebellar neurons
      (resulting in the destruction of surrounding structures) and swelling of the
      synapses (terminals of mossy fibers on granule cell dendrites) were observed. By
      contrast, the areas of intracerebral, subdural, and subarachnoid hemorrhages were
      lower in rats under conditions of forced rest.

PMID- 23113297
TI  - Content of mRNA for NMDA glutamate receptor subunits in the frontal cortex and
      striatum of rats after morphine withdrawal is related to the degree of
      abstinence.
AB  - We studied the expression of mRNA for genes, whose protein products regulate the
      glutamate/NO/cGMP signal cascade in the frontal cortex, striatum, midbrain, and
      hippocampus of rats with various degrees of spontaneous morphine withdrawal
      syndrome. The concentration of Grin2a mRNA (subunit of the NMDA glutamate
      receptor) in the frontal cortex increased mainly in animals with severe
      abstinence. By contrast, the expression of mRNA for the Grin2b subunit in the
      striatum decreased in animals with mild abstinence. Variations in the content of
      mRNA for other products of the cascade (isoforms of NO-dependent guanylate
      cyclase and cGMP-dependent protein kinase) after morphine withdrawal were not
      related to the degree of abstinence. Our results suggest that the region-specific
      expression of mRNA for certain subunits of the NMDA glutamate receptor after
      morphine withdrawal can determine the degree of abstinence.

PMID- 23113298
TI  - Can summary nitrite+nitrate content serve as an indicator of NO synthesis
      intensity in body tissues?
AB  - Studies with the use of a highly specific enzymatic sensor demonstrated that,
      contrary to the common opinion, normally nitrate is in fact not present in the
      most important physiological fluids. NO metabolites in the amniotic fluid and
      semen are mainly presented by NO donor compounds. Therefore, the intensity of NO
      synthesis can be evaluated by the total content of all its metabolites, but not
      by the widely used summary nitrite+nitrate content.

PMID- 23113299
TI  - Metric similarity of dynamic commutation processes in situ and in vitro.
AB  - The dynamics of string growth was studied in model homochiral solutions of
      biomimetics, trifluoroacetylated amino alcohols (TFAAA) in heptane, water, and
      inverted heptane-water emulsion. In heptane and water, a thick (~1 MU in
      diameter) string had a crown of thin strings on its growing terminal and these
      thin strings effectively adsorbed dissolved TFAAA. In emulsion, the strings grew
      inside the water droplets, in which this TFAAA cannot be solved, presumably due
      to transport of TFAAA molecules from heptane into water in the surface layer
      surrounding the string. Applications of these phenomena to in vivo cell
      commutation were discussed.

PMID- 23113300
TI  - Mechanisms of regeneratory effects of baikal aconite diterpene alkaloids.
AB  - Regeneratory activities of Baikal aconite alkaloids were studied on the excision
      skin wound model. Manifest wound healing effects of songorine, napelline, and
      hypaconitine were detected. The therapeutic efficiency was based on activation of
      residual mesenchymal progenitor elements. The development of this phenomenon was
      explained by the direct effects of alkaloids on precursors and by higher
      production of growth factors by the skin stromal cells. Songorine exhibited the
      most pronounced specific activity due to more significant stimulation of
      progenitor cell differentiation associated with maximum activation of the
      secretory function of the microenvironment cells.

PMID- 23113301
TI  - Role of the cholecystokinin system in anxiolytic activity of dipeptide GB-115.
AB  - We studied the effect of dipeptide GB-115, a retroanalogue of cholecystokinin-4
      with anxiolytic properties, on the behavior of outbred rats and BALB/c and
      C57Bl/6 mice induced by cholecystokinin-4 receptor agonists and yohimbine.
      Anxiogenic agents were shown to cause anxiety in rats and C57Bl/6 mice (with an
      active response to stress) in the open field test and elevated plus maze test,
      but did not modulate the behavior of BALB/c mice exhibiting a freezing response
      to emotiogenic exposure. Activation of cholecystokinin-4 type 2 receptors
      abolished the antianxiety effect of GB-115 in BALB/c mice. This dipeptide
      prevented the development of cholecystokinin-4-induced anxiety in C57Bl/6 mice
      and outbred rats. alpha(2)-Adrenoceptor antagonist yohimbine did not modulate the
      effects of GB-115 in BALB/c mice. GB-115 did not prevent the development of
      yohimbine-induced anxiety in C57Bl/6 mice. Our results confirm the data on
      phenotype-specific activity of GB-115. We conclude that cholecystokinin-4 and GB
      115 have a common pharmacological target.

PMID- 23113302
TI  - Inotropic effects of gaseous transmitters in isolated rat heart preparation.
AB  - We studied the effects of carbon monoxide and sodium hydrosulfide, hydrogen
      sulfide donor, on contractile activity of the left ventricle in Langendorf
      perfused isolated rat heart. Carbon monoxide 5*10(-5) M significantly accelerated
      sinus rhythm and left-ventricular pressure wave growth and decay. To the
      contrary, negative inotropic and chronotropic effects were observed at higher
      concentrations of carbon monoxide (10(-4), 3*10(-4) M). Sodium hydrosulfide (10(
      4)-4*10(-4) M) decreased all the parameters of left-ventricular contractive
      activity and reduced contraction rate. Carbon monoxide and hydrogen sulfide,
      which together with nitrogen oxide are qualified as a new class of gaseous signal
      compounds, may substantially modulate pumping function of the heart.

PMID- 23113303
TI  - Effect of triterpene derivatives on the total hepatocyte count in the liver of
      rats with toxic hepatitis.
AB  - We studied hepatoprotective activity of betulonic acid and its alaninamide on the
      model of combined CCl(4)- and ethanol-induced toxic liver damage in rats. The
      test substances, especially betulonic acid alaninamide, considerably reduced the
      elevated biochemical parameters in animals with toxic liver damage. Betulonic
      acid alaninamide also stimulated reparative processes in the liver (activated
      hepatocyte proliferation). Heptral (reference drug) produced no appreciable
      effects on the reparative processes. Our findings suggest that betulin
      derivatives exhibit pronounced protective properties.

PMID- 23113304
TI  - Aggravation of cyclophosphamide-induced acute neurological disorders under
      conditions of artificial acidification of chyme in rats.
AB  - The effect of artificial acidification of the intestinal content on neurological
      manifestations of acute severe cyclophosphamide intoxication was studied in rats.
      The animals were gavaged with 20 ml/kg sulfuric (0.05 M), hydrochloric, boric, or
      lactic acids (0.1 M) 3 h before intraperitoneal injections of the cytostatic in
      doses of 0, 200, 600, or 1000 mg/kg. The decrease in pH (by.0) and ammonia
      producing activity of the cecal chyme developed within 3 h after administration
      of acids. Cyclophosphamide caused hyperammonemia; glutamine/ammonia and
      urea/ammonia ratios in the blood decreased. These changes augmented after
      administration of acids (boric acid produced maximum and lactic acid minimum
      effects). Acid treatment resulted in greatest elevation of ammonia level in the
      portal venous blood and a lesser elevation in the vena cava posterior blood. Acid
      treatment promoted manifestation of cyclophosphamide neurotoxic effect and animal
      death. Hence, acidification of the chyme inhibited the formation of ammonia in
      it, while ammonia release from the gastrointestinal tract into the blood
      increased; the treatment augmented hyperammonemia and aggravated the neurological
      manifestations of cyclophosphamide intoxication.

PMID- 23113305
TI  - Effect of exercise on the expression of HSPBP1, PGLYRP1, and HSPA1A genes in
      human leukocytes.
AB  - The effects of 30-min medium-intensity exercise on the expression of genes
      encoding heat shock protein 70 (HSPA1A) and its cochaperones HSP-70-binding
      protein 1 (HSPBP1) and Tag7 (PGLYRP1) in human leukocytes were studied.
      Transcription activities of HSPA1A and PGLYRP1 genes increased immediately after
      medium-intensity exercise, while activity of HSPBP1 gene remained unchanged.
      During recovery after exercise, the expression of HSPA1A gene virtually did not
      change, while the expression of PGLYRP1 gene continued to increase and after 90
      min more than 2-fold surpassed the basal level.

PMID- 23113306
TI  - Association of FGFR3 and MDM2 gene nucleotide polymorphisms with bone tumors.
AB  - Association study of 6 candidate single-nucleotide polymorphisms (rs7921,
      rs7956547, rs3761243, rs11737764, rs6599400, rs1690916) was carried out in a
      group of patients with bone tumors of different histological structure (n=68) and
      control group of normal subjects (n=96). Significant associations of rs6599400
      and rs1690916 polymorphisms with disease risk were detected (odds ratio 2.15
      [1.06-4.24] and 0.39 [0.19-0.78], respectively). These polymorphisms were located
      in untranslated genome regions: polymorphism rs6599400 in the 5' region of
      fibroblast growth factor-3 receptor gene (FGFR3), rs1690916 in the 3' region of
      mouse MDM2 p53-binding protein homolog (MDM2). These data indicated a possible
      role of hereditary genetic factors in the formation of predisposition to bone
      sarcomas and confirmed previous findings according to which these genes should be
      regarded among the most probable factors involved in tumor development, including
      tumors of the bone and cartilage tissues.

PMID- 23113307
TI  - Tissue inhibitors of matrix metalloproteinases 1 and 2 and matrix
      metalloproteinase activity in the serum and lungs of mice with lewis lung
      carcinoma.
AB  - We studied the content of tissue inhibitors of matrix metalloproteinases 1 and 2
      (TIMP-1 and TIMP-2) and activities of matrix metalloproteinases (MMP) in the
      serum and lungs of mice with Lewis lung carcinoma metastasizing into the lung.
      Metastasizing was associated with increased serum content of TIMP-1 and TIMP-2
      (only on day 20 at the terminal stage of the tumor process). These data confirm
      the hypothesis on pro-tumorigenic role of TIMP-1 in the serum. Locally, the
      development of metastases was associated with a decrease in TIPM-1 concentration
      (day 7), an increase in TIMP-2 concentration (days 7 and 20), and elevated
      activity of MMP at all terms of the study (days 7, 15, and 20). Increased
      concentration of TIMP-2 in the lungs (but not in the serum) can be regarded as an
      indicator of Lewis lung carcinoma metastasizing.

PMID- 23113308
TI  - Expression of peroxiredoxin 1, 2, 3, and 6 genes in cancer cells during drug
      resistance formation.
AB  - We studied the expression of peroxiredoxin genes (PRDX1, PRDX2, PRDX3, and PRDX6)
      in human erythroleukemia K652, human breast carcinoma MCF-7, and human ovarian
      carcinoma SKOV-3 cells during cisplatin resistance development. It was found that
      drug resistance formation was accompanied by a significant increase in the
      expression of PRDX1, PRDX2, PRDX3, PRDX6 genes in all cancer cell strains, which
      confirms the important contribution of redox-dependent mechanisms into the
      development of cisplatin resistance of cancer cells.

PMID- 23113309
TI  - Expression of vascular endothelial growth factor receptors VEGFR1 in cultured
      multiple myeloma cells: correlation with immunophenotype and drug resistance.
AB  - We studied the expression of genes encoding vascular endothelial growth factors
      VEGF-A, VEGF-C, VEGF-D and their receptors in cell cultures of human multiple
      myeloma IM9, RPMI 1640, RPMI 8226. The studied cells did not differ by the
      expression of growth factors. Expression of VEGFR1 receptor was detected only in
      IM9 cells and VEGFR2 and VEGFR3 receptors were not expressed in multiple myeloma
      cells. A dependence between the aberrant CD45/CD56 phenotype of human multiple
      myeloma cells and VEGFR1 expression in them was revealed. The only VEGFR1
      positive IM9 cell culture was most resistant to Velcade (bortezomib).

PMID- 23113310
TI  - CYP2C9 and VKORC1 gene polymorphism is inessential for bleeding development under
      conditions of oral application of anticoagulant acenocoumarol in Russian patients
      at high risk of thromboembolic complications.
AB  - The study included 52 patients at a high risk of thromboembolic complications,
      with permanent atrial fibrillation. All patients were treated with acenocoumarol
      for 6 months and the incidence of hemorrhages was evaluated in all of them. All
      patients were genotyped by CYP2C9 and VKORC1. The presence of CYP2C9*2 and
      CYP2C9*3 alleles of CYP2C9 locus and AA genotype of VCORC1 gene polymorphic G
      1639(3673)A marker was not associated with the development of hemorrhages under
      conditions of acenocoumarol treatment (p=0.144 for CYP2C9, p=0.809 and 0.918 for
      VCORC1 in the total group and subgroup of patients with CYP2C9*1/*1 genotype,
      respectively). The search for other genetic markers of acenocoumarol efficiency
      and safety is needed for predicting the risk of hemorrhages during this
      treatment.

PMID- 23113311
TI  - Treatment of experimental ulcerative colitis.
AB  - The effects of infliximab, an anticytokine drug, on the course of inflammatory
      process was studied on the model of ulcerative colitis induced by injection of
      picrylsulfonic acid. Infliximab prevented the development of toxic dilatation and
      a drop of bioelectric activity of smooth muscles via maintenance of activity of
      the intramural nervous system neurons.

PMID- 23113312
TI  - Immunohistochemical and morphological changes in neurons and neuroglia in the
      cerebral nigrostriatal structures under conditions of experimental nigral
      neurodegeneration.
AB  - The count of dopamine-containing neurons decreased by 77%, the area of the
      remaining cells shrank by 75%, and the neuroglia doubled 4 weeks after injection
      of toxin (6-hydroxydopamine) into the compact part of the substantia nigra of the
      right cerebral hemisphere of rats, while no changes in the substantia nigra of
      the left hemisphere were observed. Neurons of the caudate nucleus were virtually
      unchanged in comparison with the intact control, while the neuroglia was
      activated: its total volume in the right hemisphere increased by 33% (50%
      increase in astrocyte count and a 25% increase of the rest neuroglia), while in
      the left hemisphere only astrocyte count increased by 20%. Astrocyte nuclei in
      the caudate nuclei of both hemispheres were enlarged by 22-23%. Hence, unilateral
      destruction of the nigral dopamine-containing neurons stimulated the neuroglia
      (particularly astroglia) in the caudate nuclei, especially on the side of damage.

PMID- 23113313
TI  - Intracellular cholestasis in HCV and HBV infection.
AB  - Structural analysis of hepatocytes in liver biopsy specimens from patients with
      hepatitis C and C+B with intracellular cholestasis was carried out. Large foci of
      bile components in hepatocytes led to cell damage, eventuating in cell
      destruction and death. The cholestatic variant of mixed infection was
      characterized by destructive necrotic changes in hepatocytes and progressive
      fibrosis of the liver. Destruction of the hepatocyte cytoplasmic organelles was
      associated with high activity of the infectious process and pronounced cytolytic
      syndrome.

PMID- 23113314
TI  - Effect of treatment with testosterone derivatives on morphometric characteristics
      and free radical oxidation in rat cerebral cortex.
AB  - Morphometric characteristics and free radical oxidation in neurons of the
      neocortex and hippocampus of male and female rats were studied 1 month after
      administration of Sustanon-250 in a dose of 8 mg/kg during the pubertal period of
      ontogeny. The weight of the brain was shown to decrease in males. In both female
      and male rats, the width of the anterior parietal lobe and the numerical density
      of neocortical and hippocampal neurons decreased. Sex differences were found in
      free radical oxidation in the cerebral cortex. The intensity of this process
      increased significantly in females, but decreased in males.

PMID- 23113315
TI  - Fluorescent methods in the study of UV-induced changes in structural and
      functional state of human blood lymphocytes.
AB  - Structural and functional state of human blood lymphocytes after exposure to UV
      light (240-390 nm) in doses of 151-1359 J/m(2) was studied by methods of laser
      flow cytofluorometry, indirect immunofluorescence, and fluorescent probes. Using
      a combination of these methods, we have showed that UV light in the specified
      doses induced changes in the surface phenotype of T cells: stimulation or
      suppression of the expression of antigen-recognizing receptor complex molecules
      (CD3, CD4, and CD8 markers) and their redistribution on the surface of
      immunocompetent cells (capping effect) with the formation of receptor clusters of
      various types.

PMID- 23113316
TI  - Classification of patients by the function of dentition, postural, and autonomic
      nervous systems.
AB  - Cluster analysis of the results of studies of the functional status of the
      dentition postural and autonomic nervous systems in 251 patients (129 men and 122
      women) aged 20-60 years was carried out. European stabilometry variant was used.
      The patients could be distributed into two groups by the results of cluster
      analysis. By functional parameters, groups 1 and 2 could be defined as patients
      with decompensated and compensated functional status, respectively. The
      characteristics of the functional status of patients in the two groups are
      presented.

PMID- 23113317
TI  - Tricolour fluorescence detection of sequence-specific DNA with a new molecular
      beacon and a nucleic acid dye TOTO-3.
AB  - We have developed a tricolor fluorescence quantitative method for sequence
      specific DNA detection using a new molecular beacon (MB) and a nucleic acid dye
      TOTO-3. This new MB is designed with two fluorophores of FAM and TAMRA instead of
      one fluorophore and one quencher of traditional MB, and a nucleotide with guanine
      base is attached directly to FAM as a quencher. In the absence of target DNA, MBs
      are in the stem-loop state. The fluorescence of FAM is absorbed by TAMRA, and the
      fluorescence of TAMRA is quenched by guanine base. Meanwhile, the interaction
      between TOTO-3 and MBs is very weak. In the presence of target DNA, MBs hybridize
      with target DNA to form a double-stranded structure. TAMRA is separated from FAM
      and guanine base, and the fluorescence of FAM and TAMRA recovers simultaneously.
      At the same time TOTO-3 binds to double-stranded DNA, the fluorescence of TOTO-3
      significantly enhances. In this strategy, the false-positive signals of MBs
      caused by non-specific interactions can be distinguished by the change of the
      ratio of the total fluorescence intensities of FAM and TAMRA to that of TOTO-3 at
      different concentrations of target DNA. In the simple sample, the detection of
      target DNA can be achieved with the total fluorescence intensity of three dyes,
      which results in a significant improvement of the detection sensitivity. In the
      complex sample, the detection of target DNA can be achieved with the fluorescence
      intensity of TOTO-3 which can overcome the false-positive signals of MBs and
      improve the detection accuracy.

PMID- 23113318
TI  - Graphene oxide modified light addressable potentiometric sensor and its
      application for ssDNA monitoring.
AB  - A light addressable potentiometric sensor (LAPS) is a kind of silicon based
      semiconductor sensor, and surface modification is a fundamental problem for its
      application in biological fields. Graphene oxide (GO) based biochemically
      activated LAPS were proposed, called GO-LAPS. The GO-LAPS were applied to
      monitoring single strand DNA (ssDNA) probe immobilization and its hybridization
      with complementary ssDNA molecules of different chain lengths (30, 21 and 14 base
      pairs, respectively). It was discovered that the curves of LAPS' currents versus
      analyte concentrations for ssDNA probe binding and the target ssDNA hybridization
      were different. Explanations were proposed based on the semiconductor's surface
      electric-field-effect and the electrical properties of ssDNA molecule. Moreover,
      comparisons between GO-LAPS and LAPS without GO modification were carried out.
      Enhanced response currents of GO-LAPS were reported experimentally and analyzed
      theoretically based on X-ray photoelectron spectroscopy (XPS) of GO-LAPS. The
      limitation of target ssDNA monitoring was 1 pM to 10 nM, which suggested that
      this LAPS based platform could be developed as a sensitive means for short chain
      ssDNA detection.

PMID- 23113319
TI  - Turn-on fluorescent chemosensor for Zn(II) via ring opening of rhodamine
      spirolactam and their live cell imaging.
AB  - A new rhodamine based selective and sensitive turn-on fluorescent
      Zn(2+)chemosensor has been developed. A prominent fluorescence enhancement was
      found in the presence of Zn(2+), which was accompanied by changes in the
      absorption spectrum. The new sensor showed 'naked-eye' detection of Zn(2+) ions:
      a color change of the solution from colorless to pink. Furthermore, by means of
      confocal laser scanning microscopy experiments, it has been demonstrated that it
      can be used as a fluorescent probe for monitoring Zn(2+) in living cells.

PMID- 23113320
TI  - Electrochemical incorporation of hemin in a ZnO-PPy nanocomposite on a Pt
      electrode as NO(x) sensor.
AB  - An electrochemical NO(x) sensor was fabricated based on the incorporation of
      hemin on a ZnO-PPy nanocomposite modified Pt electrode. Scanning electron
      microscopy, energy dispersive X-ray analysis and cyclic voltammetry were used to
      confirm the successful stepwise assembly procedure for the sensor. The
      electrocatalytical behavior of the sensor was investigated by cyclic voltammetry.
      The hemin-ZnO-PPy-Pt electrode exhibited characteristic hemin reversible redox
      peaks at 0.035 V and -0.11 V vs. Ag/AgCl respectively. The hemin-ZnO-PPy-Pt
      electrode exhibited 3-fold enhanced electrocatalytic activity towards NO(x)
      compared to the hemin-PPy-Pt electrode. The electrocatalytic response of the
      sensor was proportional to the NO(x) concentration in the range of 0.8 to 2000
      MUM (r(2) = 0.9974) with a sensitivity of 0.04 MUA MUM(-1) cm(-2) and detection
      limit of 0.8 MUM for the hemin-ZnO-PPy-Pt electrode. The low detection limit,
      wide linear range and enhanced sensitivity of the present sensor make it valuable
      for potential applications. In addition, this sensor exhibited good
      reproducibility and stability.

PMID- 23113322
TI  - Underwater superoleophilicity to superoleophobicity: role of trapped air.
AB  - The interesting oil-wetting behavior to a superamphiphobic surface in water has
      been investigated. We demonstrated that the trapped air can tune the underwater
      wettability of the surface, changing from superoleophilic to superoleophobic. The
      trapped air in the grooves of the superamphiphobic surface can cause the
      significant change of the three-phase contact line (TCL).

PMID- 23113321
TI  - Tattoo-based potentiometric ion-selective sensors for epidermal pH monitoring.
AB  - This article presents the fabrication and characterization of novel tattoo-based
      solid-contact ion-selective electrodes (ISEs) for non-invasive potentiometric
      monitoring of epidermal pH levels. The new fabrication approach combines
      commercially available temporary transfer tattoo paper with conventional screen
      printing and solid-contact polymer ISE methodologies. The resulting tattoo-based
      potentiometric sensors exhibit rapid and sensitive response to a wide range of pH
      changes with no carry-over effects. Furthermore, the tattoo ISE sensors endure
      repetitive mechanical deformation, which is a key requirement of wearable and
      epidermal sensors. The flexible and conformal nature of the tattoo sensors enable
      them to be mounted on nearly any exposed skin surface for real-time pH monitoring
      of the human perspiration, as illustrated from the response during a strenuous
      physical activity. The resulting tattoo-based ISE sensors offer considerable
      promise as wearable potentiometric sensors suitable for diverse applications.

PMID- 23113323
TI  - The genomics revolution: relevance in healthcare  today and tomorrow.

PMID- 23113324
TI  - John Abercrombie (1780-1844).

PMID- 23113325
TI  - Outbreak news. Dengue fever in Madeira,Portugal.

PMID- 23113326
TI  - Outbreak news. Marburg haemorrhagic fever, Uganda.

PMID- 23113327
TI  - Progress towards poliomyelitis eradication in Chad, January 2011- August 2012.

PMID- 23113328
TI  - Monthly report on dracunculiasis cases, January-August 2012.

PMID- 23113329
TI  - Antigenic and genetic characteristics of zoonotic influenza viruses and
      development of candidate vaccine viruses for pandemic preparedness.

PMID- 23113330
TI  - [Studies in chicken genetics: commemorating the 120th anniversary of the
      outstanding Soviet geneticist A. S. Serebrovsky (1892-1948)].
AB  - The paper highlights the research of A. S. Serebrovsky in chicken genetics,
      including gene mapping and inheritance of morphological traits. Genetic formulas
      for several breeds are presented. The data of genetic surveys for local chicken
      populations from 23 regions of the former Soviet Union are also reviewed. The
      personal data of the authors on the morphotypological characteristics of
      different chicken breeds are given and discussed.

PMID- 23113331
TI  - [Role of the Drosophila melanogaster hrs gene in wing formation].
AB  - The Hrs (hepatocyte growth factor receptor tyrosine kinase substrate) protein is
      an endosomal protein whose function is to transport receptor tyrosine kinases
      from early endosomes to lysosomes. Since receptor tyrosine kinases are involved
      in various signaling pathways, HSR defects lead to various malformations. A study
      of the role of the hrs gene in wing development in Drosophila confirmed that the
      gene is involved in the formation of the D/V boundary of the wing imaginal disk
      and suggested a new role in wing vein refinement for the gene. Structural
      analysis of the hrs gene transcripts indicated that transcript B is responsible
      for vein refinement.

PMID- 23113332
TI  - [Set of module vectors for stable or transient expression of heterologous genes
      in plants].
AB  - A set of module vectors for stable or transient gene expression in plants was
      constructed with regard to the majority of factors ensuring efficient
      heterologous gene expression in plants. The vectors are convenient to clone new
      regulatory elements and genes of interest via simple molecular cloning
      procedures. The vectors can be used to obtain transgenic plants with stable
      heterologous gene expression as well as to achieve transient expression because
      one vector includes the gene for the tomato bushy stunt virus p19 protein, which
      acts as a suppressor of posttranscriptional gene silencing.

PMID- 23113333
TI  - [Properties of the new D3-like Pseudomonas aeruginosa bacteriophage phiPMG1:
      genome structure and prospects for the use in phage therapy].
AB  - Results of studying the novel virulent phage phiPMG1 active on Pseudomonas
      aeruginosa are presented. phiPMG1 was shown to exhibit detectable homology and
      resemblance in the total genome structure with temperate converting phage D3.
      Phage phiPMG1 differs from D3 in that it fails to stably lysogenize bacteria and
      can grow on strains carrying plasmids that cause growth inhibition of phage D3
      and some other phages. This significantly diminishes the probability of
      horizontal gene transfer with phage phiPMG1 and suggests the possible employment
      of this phage in phage therapy. A comparison of genome structures in phages
      phiPMG1 and D3 demonstrated not only high homology of 65 genes, but also the
      presence in the phiPMG1 genome of 16 genes that were not recorded in the files of
      NCBI database. Apparently, the evolution of genomes in phages of this species is
      mostly associated with migrations into other species of bacteria and
      recombinations with phages of other species (for example, F116). Detailed
      structural analysis a genome region in which the essential nonhomology is
      exhibited between three D3-like phages (D3, phiPMG1, and PAJU2) revealed that the
      phiPMG1 genome supposedly is phylogenetically closer than the others to the
      genome of a hypothetical ancestor phage belonging to this species.

PMID- 23113334
TI  - [Low level of allozyme polymorphism in relict aquatic plants of the Far East
      Nelumbo komarovii Grossh. and Euryale ferox Salisb].
AB  - Using allozyme analysis, genetic variation of two relict aquatic plants from
      Primorsky krai, Komarov lotus (Neliumbo komarovii Grossh.) and Gorgon plant
      (Euryale ferox Salisb.), was examined. The absence of allozyme variation in the
      Primorye populations of Neliumbo komarovii along with low polymorphism level in
      the population of Euryale ferox (P95 = 7.69; A = 1.07; Ho = 0.072; He = 0.038)
      was demonstrated. Since the data for the species examined are reported for the
      first time ever, the pheonotypes and genetic interpretation of the enzyme systems
      tested are presented. The izoenzyme profiles of N. komarovii were compared with
      the data reported for N. nucifera from China. The absence ofallozyme variation in
      N. komarovii, along with extremely low level of variation revealed for E. ferox,
      is discussed in association with the evolutionary histories of these species,
      their dispersal after the Pleistocene-Holocene cooling, and survival on this
      territory in range boundaries.

PMID- 23113335
TI  - [Systematics and genegeography of Juniperus communis inferred from isoenzyme
      data].
AB  - Using isoenzyme analysis, 35 populations of Juniperus communis L. from various
      parts of the Russian species range and by one population from Sweden and Alaska
      were studied. The total sample size was 1200 plants. As a result, the existence
      ofJ. communis var. oblonga in North Caucasus and J. communis var. depressa in
      North America was confirmed, but genetic differences between J. communis var.
      communis and J. communis var. saxatilis were not detected in the main part of the
      Russian species range (European part of Russia, Ural, Siberia). These populations
      proved to be genetically uniform with the same predominant allelic frequencies,
      which may evidence recent settling of this species from one of Central or East
      European refugium. J. communis var. saxatilis from northeastern Russia inhabiting
      the region behind Verkhoyansk mountain and Russian Far East showed considerable
      differentiation in frequencies of alleles at three loci and geographical
      subdivision. These populations also exhibit high intrapopulation variation. This
      can be connected with the refugium in this territory. The origin of this group is
      probably connected with migrations from Central Asia (Tibet) in the direction to
      northeastern Russia along mountains connecting Central and North Asia. It is also
      assumed that migrations of this species previously proceeded across the Beringian
      land bridge.

PMID- 23113336
TI  - [Study of the association between alleles of the growth hormone receptor and
      prolactin receptor genes of bulls and the milk productivity of their daughters].
AB  - A substitution of thyrosine for phenylalanine (F297Y) in the transmembrane domain
      of the growth hormone receptor (GHR) was tested for significance for breeding
      evaluation of bulls of the holstenized Black-and-White breed. The breeding value
      was estimated by the method of daughter yield deviation to contemporaries with
      modification. The frequency of genotype FF in the bulls examined was 0.37, lower
      than in Holstein bulls (0.67). The F297Y substitution exerted the greatest effect
      on the milk fat content (1.5 sigma) and milk yield (0.8 sigma) and a lower effect
      on the milk fat yield (0.6 sigma), milk protein yield (0.5 sigma), and milk
      protein content (0.6 sigma). The GHR4.2 single nucleotide substitution (SNP) in
      the promoter of the GHR gene did not affect the milk production traits. A
      substitution of asparagine for serine (S18N) in the transmembrane domain of the
      prolactin receptor (PRLR) was also examined, but it did not significantly affect
      the milk production parameters. The results are discussed in the context of the
      hypothesis that multiplicity of causal mutations of a particular gene is common
      and should be taken into account in the genetics of quantitative traits.

PMID- 23113338
TI  - [Polymorphism of the mtDNA control region in wild reindeer Rangifer tarandus
      (Mammalia: Artiodactyla) from the European part of Russia].
AB  - Genetic diversity ofwild reindeer (Rangifer tarandus) inhabiting the European
      part of Russia, including Komi Republic, Arkhangelsk oblast, Murmansk oblast, and
      the Republic of Karelia was characterized using sequence polymorphism of the
      mtDNA control region. Despite of currently low population number of wild
      reindeer, they were characterized by a high level of genetic diversity (pi =
      0.018; H= 0.872 to 0.914). Phylogenetic analysis showed close relationships
      between European reindeer and wild reindeer of Siberia. In reindeer from Murmansk
      oblast a haplotype in common with the wild reindeer form Southwestern Norway was
      described. The reindeer sample examined contained no haplotypes earlier described
      for the reindeer of Central Norway. It is suggested that in recent past wild
      reindeer from the European north of Russia formed one population with the
      reindeer from the north of the Asian part of Eurasia.

PMID- 23113339
TI  - [Genetic epidemiological study of monogenic hereditary diseases in the Republic
      of Tatarstan: population dynamic factors determining the differentiation of the
      load of hereditary diseases in five districts].
AB  - A genetic epidemiological study has been performed in five districts of the
      Republic of Tatarstan, Russia: Arsky, Atninsky, Kukmorsky, Buinsky and
      Drozhzhanovsky raions. The total size of the population surveyed is 188 397
      people. Tatars accounted for 77.13% of the population analyzed (145466 people)
      and were represented by two main ethnic groups: Kazan Tatars and Mishars. The
      medical genetic study encompassed the total population of the districts,
      irrespective of ethnicity, and was carried out according to the standard protocol
      developed in the Laboratory of Genetic Epidemiology of the Research Center for
      Medical Genetics of the Russian Academy of Medical Sciences. After segregation
      analysis, the prevalence rates of the main types of monogenic hereditary
      disorders (MHDs), i.e., autosomal dominant (AD), autosomal recessive (AR), and X
      linked diseases, have been calculated for the total population of the five
      districts and for Tatars alone. The prevalence rates ofAD, AR, and X-linked
      diseases considerably vary in different subpopulations. The largest difference in
      the MHD prevalence rate has been found between the rural and urban populations.
      The overall prevalence rate of MHDs was one patient per 293 urban residents and
      populations and one patient per 134 rural residents, with a wide variation
      between subpopulations, from 1 : 83 people in the rural population of Atninsky
      raion to 1: 351 people in the town of Kukmor. Comparison of the MHD prevalence
      rate in Tatars with those in populations surveyed earlier has shown that the
      characteristics of the load of MHDs in the Tatar population are similar to those
      in some districts of the republics of Bashkortostan, Udmurtia, Mari El, and
      Chuvachia. In Russian populations of European Russia, the MHD prevalence rates
      are substantially lower. Correlation analysis has shown high (r = 0.5-0.9)
      significant correlations between the local inbreeding (a), the im index, the
      random inbreeding (F(ST)), and the AD and AR prevalence rates in the Tatar
      population. This analysis has demonstrated that genetic drift is the main
      population dynamic factor determining the MHD load in the Tatar population.

PMID- 23113340
TI  - [The spectrum of CLCN1 gene mutations in patients with nondystrophic Thomsen's
      and Becker's myotonias].
AB  - Thomsen's and Becker's diseases are the most prevalent nondystrophic myotonias.
      Their frequency varies, according to different sources, from 1 : 100 000 to 1 :
      10 000. Thomsen's myotonia is autosomal dominant, and Becker's myotonia is
      autosomal recessive. Both diseases result from mutations of the CLCN1 gene
      encoding chloride ion channels of skeletal muscles. Molecular genetic analysis of
      the CLCN1 gene has been performed in patients with diagnoses of nondystrophic
      Thomsen's and Becker's myotonias living in the Russian Federation. A sample of 79
      unrelated probands with nondystrophic Thomsen's and Becker's myotonias and 44
      their relatives has been formed in the Laboratory of DNA Diagnosis of the Medical
      Genetic Research Center of the Russian Academy of Medical Sciences. Forty CLCN1
      gene mutations have been found in a total of 118 chromosomes of 66 probands,
      including 21 familial and 45 sporadic cases. About half the mutations detected
      (45%) have been found for the first time; they are not described in the SNP
      database (ncbi.nlm.nih.gov). The following mutations (substitutions) have been
      detected in more than one chromosome, accounting for a total of 59.3% of
      chromosomes with mutations: Glyl90Ser (5.9%), c.1437-1450del14 (9.3%), Ala493Glu
      (5.1%), Thr550Met (3.4%), Tyr686Stop (5.1%), and Arg894Stop (30.5%).

PMID- 23113341
TI  - [Chromosomal polymorphism in the populations of malaria mosquito Anopheles
      messeae (Diptera, Culicidae) at the south of Russian Plain].
AB  - Zonal features of the geographic distribution of chromosomal inversions in the
      populations of An. messae at the south of the Russian Plain were examined. The
      An. messae was identified based on morphological characters and cytogenetically.
      The chromosomal inversions identified in populations of An. messae comprised XL1,
      XL4, 2R1, 3R1, and 3L1. Inversion XL4 was endemic and found with low frequency
      (2%) in Penza oblast and Moscow oblast. Based on the population karyotype
      structure similarity, on the territory of Russian Plain, three zones
      (southwestern, southeastern, and central) were identified. Central zone was
      characterized by higher levels of inversion polymorphism in all chromosomes,
      except arm 3L. In the two southern zones, high frequency of the XL0 inversion,
      along with complete absence of homo- and heterozygotes for the 2R1 inversion, and
      high proportion of the individuals with inversion 3L1 was observed. Specific
      feature of southeastern zone was the increased frequency ofhetero- and
      homozygotes for the 3R1 and 3L1 inversions. Zonal differences reflected adaptive
      character ofchromosomal polymorphism and pointed to hierarchic organization of
      the species population structure.

PMID- 23113337
TI  - [Phylogeography of pacific herring Clupea pallasii from Eurasian seas].
AB  - Eleven samples of Pacific herring from the four seas of Eurasia (Sea of Japan,
      Sea of Okhotsk, Bering Sea, and White Sea), and one sample of Atlantic herring
      were analyzed. Complete and partial sequences of the mtDNA control region with
      the sizes up to 1071 bp were used. To verify the haplogroups identified,
      additional sequencing of the cytochrome oxidase I gene was performed. It was
      demonstrated that Pacific herring from the seas of Eurasia belonged to one
      mitochondrial haplogroup. The gene flow between the localities from different
      parts of the Far Eastern sea basins was about 11% per locality, per generation,
      which led to constant leveling of herring intraspecific differentiation. The data
      presented gave no reasons for subdivision of the herring populations in
      accordance to ecological characters (lacustrine and marine). Analysis of global
      molecular variance (global AMOVA) demonstrated that in Asian water basins, more
      than 98% of molecular polymorphism was found within the samples at the low level
      of significance (p < 0.05).

PMID- 23113342
TI  - [Mammalian telomere biology].
AB  - Review is devoted to detailed consideration of the functioning in normal and
      immortal cells of one of the main chromosomal regions, telomeres, being dynamic
      nucleoprotein structures that cap the ends of eukaryotic chromosomes, protecting
      them from degradation and end-to-end fusion. The role of telomeres in maintenance
      of genome stability and cell division was also analyzed. Telomere function
      depends on many interrelated parameters such as telomerase activity, status of
      the telomere safety complex shelterin and telomere associated proteins (factors
      of replication, recombination, and reparation of DNA breaks, and so on). We have
      focused on mechanisms of telomere length control in normal and immortal cells as
      well as in cells containing active telomerase and cells wherein it is absent. We
      have analyzed the features attributed to alternative telomere lengthening, namely
      in view of recently discovered additional mechanism of telomere shortening by
      trimming of t-cycles. We have viewed a possibility of expression in normal
      mammalian cells of both telomerase dependent and recombinational ways of telomere
      length control and the role of shelterin proteins in choice of the one of them as
      the dominant way. The role oftelomeres in spatial organization of nucleus, in
      mitosis and meiosis has been also considered. Diversity of telomere organization
      in mammalians including unusual telomeres in Iberian shrews has been discussed.

PMID- 23113343
TI  - [Oncolytic adenoviruses in anti-cancer therapy: current status and perspectives].
AB  - Lytic viral infection results in production of viral progeny, and lysis of the
      infected cells. Tumor cells are usually more sensitive to virus infection.
      Studies of viral oncolysis indicate that it could represent a promising
      alternative approach to cancer therapy. The ability of viruses to kill
      selectively cancer cells had been noticed for quite a long time ago. However,
      only in recent years, based on deeper understanding of molecular biology of
      viruses and the cell and due to the development of modern methods for directed
      modification of viruses, there emerged a real opportunity for development of
      virus variants with improved therapeutic potential. Adenoviruses represent one of
      the most studied models of oncolytic viruses. The DNA-containing viruses are very
      suitable for genetic manipulation and show minimal pathogenicity. The review
      summarizes data on directions and approaches aiming generation of highly
      efficient variants of oncolytic adenoviruses. The approaches include introduction
      of directed genetic modifications into viral genome, accelerated selection of
      oncolytic viral variants following treatment with mutagens, the use of
      adenoviruses as vectors for introduction of therapeutic gene products,
      optimization of viral delivery systems, minimalization of negative effects from
      the host immune system etc. The dynamic development of studies in the field holds
      promise for introduction into clinical practice of many variants of oncolytic
      adenoviruses in the very near future.

PMID- 23113344
TI  - Molecular cloning and characterization of a new cDNA sequence encoding a venom
      peptide from the centipede Scolopendra subspinipes mutilans.
AB  - Many studies have been performed on venomous peptides derived from animals.
      However, little of this research has focused on peptides from centipede venoms.
      Here, a venom gland cDNA library was successfully constructed for the centipede
      Scolopendra subspinipes mutilans. A new cDNA encoding the precursor of a venom
      peptide, named SsmTx, was cloned from the venomous gland cDNA library of the
      centipede S. subspinipes mutilans. The full-length SsmTx cDNA sequence is 465 nt,
      including a 249 nt ORF, a 45 nt 5' UTR and a 171 nt 3' UTR. There is a signal
      tail AATAAA 31 nt upstream of the poly (A) tail. The precursor nucleotide
      sequence of SsmTx encodes a signal peptide of 25 residues and a mature peptide of
      57 residues, which is bridged by two pairs of disulfide bonds. SsmTx displays a
      unique cysteine motif that is completely different from that of other venomous
      animal toxins. This is the first reported cDNA sequence encoding a venom peptide
      from the centipede S. subspinipes mutilans.

PMID- 23113346
TI  - [The impact of Ty3-gypsy group retrotransposon Lila on D-genome specificity of
      wheat Triticum aestivum L].
AB  - An analysis of the primary structure of BAC clone 112D20 T. aestivum, that
      contains D-genome specific Ty3-gypsy-retrotransposon Lila is presented. PCR
      analysis of nulli-tetrasomic and deletion lines of T. aestivum allowed to
      localize this BAC clone in the distal region of the long arm of chromosome 5D.
      Characteristic feature of BAC clone 112D20 is a high concentration of Ty3-gypsy
      retrotransposons (61.7%), and low content of the genes (1.2%). Only a single open
      reading frame was revealed homologous to an unknown gene of Ae. tauschii.
      Specific to the D-genome Ty3-gypsy-retrotransposon Lila in the BAC clone 112D20
      is 14 kb in length and contains unequal in size long terminal repeats. The data
      of in situ hybridization and PCR analysis of different Triticeae species suggest
      that this retroelement was amplified within the ancestral species of Ae.
      tauschii, the donor D-genome. The suggested time of amplification based on
      estimation of insertion time of Lila 112D20 is 1.7 million years, which
      corresponds to the formation of the first allopolyploid forms of wheat. Based on
      comparison with the previously obtained data, it is concluded that the
      amplification ofretroelements specific to each genome of wheat took place during
      formation of the diploid progenitors of these genomes.

PMID- 23113345
TI  - Cloning and expression of a novel antifreeze protein AFP72 from the beetle
      Tenebrio molitor.
AB  - A novel antifreeze protein AFP72 cDNA (GenBbank accession No. AY929389) was
      obtained by RT-PCR from Tenebrio molitor. The 216 bp fragment encodes a protein
      of 72 amino acid residues. Sequence analysis revealed that the cDNA displays a
      high degree of homology with T. molitor antifreeze proteins, ranging up to
      90.78%. Recombinant plasmids pMAL-p2X-afp72 and pMAL-c2X-afp72 were transferred
      into E. coil TBI to induce a MBP fusion protein by IPTG. The target fusion
      protein was released from the periplasm and cytoplasm by the cold osmotic shock
      procedure and sonication respectively. The content of the fusion protein came up
      to 38.9 and 41.5% of the total dissolved protein, respectively. The fusion
      protein was purified through an amylose affinity column, and incised by factor
      Xa. Molecular sieve chromatography was used to achieve a high state of purity of
      the target protein. The purified target protein displayed a single band in SDS
      PAGE. The fusion protein was shown to increase resistance to low temperatures in
      bacteria. This finding could help in further investigations of the properties and
      function of antifreeze proteins.

PMID- 23113347
TI  - [A new construct of dna reporter for immuno-PCR].
AB  - A new construct of DNA reporter has been designed for protein quantification by
      immuno-PCR. It has been shown that amplification efficiency of a reporter that
      contains a fragment of human adenovirus 2 flanked by homoprimer sequences is much
      higher vs. standard PCR format based on use of two different primers. Application
      of a new construct and its homoprimer-based detection opens a way to a
      significant increase in the immuno-PCR sensitivity and the efficiency of single
      molecule PCR.

PMID- 23113348
TI  - Polysaccharide-free nucleic acids and proteins of Abelmoschus esculentus for
      versatile molecular studies.
AB  - Abelmoschus esculentus (okra) is one of the polysaccharide rich crop plants. The
      polysaccharides interfere with nucleic acids and protein isolation thereby
      affecting the downstream molecular analysis. So, to understand the molecular
      systematics of okra, high quality DNA, RNA and proteins are essential. In this
      study we present a method for extracting genomic DNA, RNA and proteins from
      polysaccharide rich okra tissues. The conventional extraction procedures were
      integrated with purification treatments with pectinase, RNase and proteinase K,
      which improved the quality and quantity of DNA as well. Using SDS, additional
      washes with CIA and NaCl precipitation improved the RNA isolation both
      quantitatively and qualitatively. Finally, ammonium acetate mediated protein
      precipitation and re-solubilization increased the quality of total protein
      extracts from the okra leaves. All of the methods above not only eliminated the
      impurities but also improved the quality and quantity of nucleic acids and
      proteins. Further, we subjected these samples to versatile downstream molecular
      analyses such as restriction endonuclease digestion, RAPD, Southern, reverse
      transcription-PCR and Western analysis and were proved to be successful.

PMID- 23113350
TI  - [Three patterns of trypanosomatid cryptogene structural organization].
AB  - We sequenced a number of cryptogenes from previously unstudied species of
      homoxenous trypanosomatids belonging to the different phylogenetic groups and
      found new examples of editing domain length reduction for A6 and COIII. The
      comparative analyzes of sequences allows to divide the cryptogenes in three
      groups (patterns) according to the degree of primary structure conservation and
      editing domain length variation. We discuss the possible factors which influence
      the cryptogene's structure and evolutionary behavior. Also we demonstrate
      alternative editing of rps12 transcript in Wallaceina sp. Wsd.

PMID- 23113349
TI  - [The structure of replication initiation region of Pseudomonas IncP-7
      streptomycin resistance plasmid Rms148].
AB  - Pseudomonads' IncP-7 plasmids make significant contribution to the environmental
      biodegradative potential and sometimes harbour antibiotic resistance genes. More
      than 30 years plasmid Rms148 is used as archetypal P-7 plasmid in microbiological
      incompatibility tests. However, the structure of its basic replicon was not
      described up to now, as well as phylogenetic relationships between all known
      plasmids within the IncP-7 group were not studied. In the frames of this work we
      have constructed two primer pairs to amplify main components of P-7 replication
      initiation region, and subsequent screening of repA intragenic polymorphism was
      made using laboratory collection of IncP-7 plasmids. Minimal replicon of Rms148
      was constructed and its nucleotide sequence was determined to be identical to
      repA-oriVof known P-7 plasmids on 81-83% and forming separate branch on
      appropriate phylogenetic tree. Additionally, repA seems to be more conservative
      between group members compared with putative oriV region. Deduced amino acid
      sequence and predicted secondary and tertiary structures of Rms148 RepA protein
      allow us to make assumption about similar to unclassified cryptic plasmid pPS10
      model of replication initiation for IncP-7 group members.

PMID- 23113351
TI  - The microRNA-29 plays a central role in osteosarcoma pathogenesis and
      progression.
AB  - Osteosarcoma is the most common type of bone cancer, with a peak incidence in the
      early childhood. The relationship between microRNAs (miRNAs) and cancer
      development attracted more and more attention over the last few years. Members of
      the miRNA-29 family, including miRNA-29a, miRNA-29b, and miRNA-29c were shown to
      participate in the development of rhabdomyosarcoma and hepatocarcinogenesis.
      Here, it has been demonstrated miRNA-29a and miRNA-29b expression levels to be
      downregulated in most of the osteosarcoma tissues (23 from 30). Besides, miRNA
      29a displayed ability to induce apoptosis in both U2OS and SAOS-2 osteoblastic
      cells. While miRNA-29 members induced apoptosis through p53 gene activation, the
      effect of miRNA-29a on osteoblastic cells was independent on p53 expression
      level. Moreover, Bcl-2 and Mcl-1 were earlier demonstrated to be the direct
      targets of miRNA-29 in many types of cancer tissues and cancers. In both U2OS and
      SAOS-2 osteoblastic cell types, overexpression of miRNA-29a also downregulated
      Bcl-2 and Mcl-1, while silencing of miRNA-29a increased their expression. In
      addition, enhanced expression of miRNA-29a increased the expression of two tumor
      suppressor genes, E2F1 and E2F3. In summary, data obtained highlight the role of
      miRNA-29a in the regulation of osteoblastic cell apoptosis by silencing Bcl-2 and
      Mcl-1 and inducing E2F1 and E2F3 expression.

PMID- 23113352
TI  - Alpha-melanocyte stimulating hormone suppresses the proliferation of human
      tenon's capsule fibroblast proliferation induced by transforming growth factor
      beta 1.
AB  - Alpha-melanocyte stimulating hormone (alpha-MSH) is a proopiomelanocortin
      derivative and a multi-function neuropeptide, well know for its pigment-inducing
      capacity, inhibitory action on proinflammatory cytokines and chemoattractant
      cytokines, and suppressive action on collagen synthesis. Human Tenon's capsule
      fibroblasts (HTF) are the main effector cells in the initiation and mediation of
      wound healing and fibrotic scar formation after trabeculectomy. In this study the
      effects of alpha-MSH on proliferation of HTF stimulated by transforming growth
      factor beta1 (TGF-beta1), have been investigated and discussed. Fibroblasts were
      cultured in Dulbecco's modified Eagle's medium (DMEM) in the control group, and
      in DMEM with TGF-beta1 at concentration of 10(-12) M in the TGF-beta1 group, and
      DMEM with 10(-12) M TGF-beta1 and alpha-MSH ranging from 0, 10(-8) to 10(-4) M in
      the TGF-beta1/alpha-MSH groups. Cell proliferation was assessed 48 h later by the
      CellTiter 96 Aqueous One Solution Cell Proliferation Assay. After administration
      of TGF-beta1 at a concentration of 10(-12) M, or TGF-beta1 at 10(-12) M plus
      alpha-MSH at 10(-6) M, the mRNA level of type I (alpha1) collagen, fibronectin,
      TNF-alpha, intercellular cell adhesion molecule-1 (ICAM-1), vascular cell
      adhesion molecule-1 (VCAM-1), MMP-1, MMP-2, TIMP-1, and TIMP-2 in HTF were
      analyzed using the real time reverse transcription polymerase chain reaction.
      Alpha-MSH demonstrated an inhibitory effect on the proliferation of HTF induced
      by TGF-beta1 in a dose-dependent manner, when the concentration was lower than
      10(-5) M, and a suppressive effect on the mRNA expression of type I (alpha1)
      collagen, TNF-alpha, ICAM-1 and VCAM-1, which were up-regulated by TGF-beta1. Our
      results showed a reverse effect of alpha-MSH on the imbalance between MMPs and
      TIMPs compared with TGF-beta1. Based on all these results, we conclude that alpha
      MSH could effectively suppress HTF proliferation and modulate correlative genes
      in collagen synthesis stimulated by TGF-beta1, which implies that alpha-MSH could
      be exploited in the treatment of conjunctival fibrotic scar disorder.

PMID- 23113353
TI  - Differential regulation of microRNA expression in irradiated and bystander cells.
AB  - The ionizing radiation (IR) induces a variety of biological effects in irradiated
      cells. Additionally, the irradiated cells communicate with unirradiated cells and
      induce changes in them through a phenomenon termed as the bystander effect. The
      nature of the bystander effect signal and how it impacts unirradiated cells
      remains to be discovered. Examination of molecular changes in bystander cells due
      to signals from irradiated cells could lead to the identification of the pathways
      underlying the bystander effect. To gain insight into the molecular pathways
      affected by the transmission of signal from irradiated cells to bystander cells,
      we monitored the microRNA (miRNA) transcriptional changes. miRNAs control gene
      expression at the posttranscriptional level. In previous studies from our
      laboratory the modulation of miRNA in irradiated human cells were identified. In
      the present work human lymphoblasts TK6 cells in a medium exchanged bystander
      effect model system were used to analyze miRNA expression alterations by
      employing the real time RT-PCR technology. The relative expression of several
      miRNAs involved in RAS, c-MYC and BCL2 gene regulation were examined. The let-7
      family of miRNAs was upregulated in irradiated cells but most of these miRNAs
      remained repressed in bystander cells. The miR-17-3p, miR-19b, and miR-18a were
      upregulated in irradiated cells but were repressed in the bystander cells. The
      miR-17-5p, miR-142-3p, miR-142-5p, and miR-19a were induced only for a short time
      in bystander cells. The miR-15a, miR-16, miR-143, miR-145, miR-155, and miR21
      were upregulated in irradiated TK6 cells. While the expression of miR-15a, miR
      16, miR-155, and miR-21 was repressed, the miR-143 and miR-145 expression was
      induced in bystander cells. These results indicate the involvement of miRNA
      modulation in irradiated and bystander cells.

PMID- 23113354
TI  - [Affect of deoxynojirimycin derivatives on hepatitis C virus morphogenesis].
AB  - Viral hepatitis C is one of the wide-spread and dangerous human diseases. The
      choice of drugs for treatment of chronic hepatitis C virus (HCV) infection is
      limited and prophylactic vaccines do not exist. Thus, the development of new
      antiviral strategies and substances are of great importance. The targeting of
      viral morphogenesis might be used as an alternative approach to existing
      strategies of HCV blocking. The glycosylation of viral envelope proteins is an
      important step of viral particle morphogenesis that determines the correct
      assembly of HCV virions. The derivatives of glucose analog deoxynojirimycin (DNJ)
      -inhibitors of alpha-glucosidase can impair the assembly of structural proteins
      and HCV particle formation. In the present work the affect of alkylated
      derivatives of DNJ N-pentyl-DNJ and N-benzyl-DNJ to HCVmorphogenesis in a model
      system insect cells producing three viral structural proteins with formation of
      virus-like particles was studied. Intracellular N-glycosylation of HCV envelope
      glycoproteins was shown to be impaired by DNJ derivatives. At 1 mM concentrations
      of these substances the level of gpE1 and gpE2 glycoproteins increase and their
      electrophoretic mobility decrease which seems to be due to inhibition of a
      glucosidase in endoplasmic reticulum and accumulation of hyperglycosylated N
      glycans in HCV glycoproteins. The interaction of the latters with calnexin leads
      to formation of unproductive dimers and bloks productive assembly of virus-like
      particles.

PMID- 23113355
TI  - [Guest peptide insertions into the surface loops of alkaline phosphatase].
AB  - The paper presents the description of the experiments in line with the rational
      concept for the "safe" insertion of guest polypeptides into the alkaline
      phosphatase with the minimal influence of the inserts on the enzymatic activity
      of the protein. Several approaches are described in the paper for the surface
      loop length estimation and two loops were used as the sites for guest peptides
      introduction by gene engineering technique. The experiments clearly demonstrate
      that insertions of several peptides after Ala218 of alkaline phosphatase (the
      site was selected by loop length analysis) do not block the activity of the
      enzyme. According the experimental data, the selection of the loops for the guest
      peptides insertion can be defined by the mobility of backbone dihedral angles
      during molecular dynamics simulation of alkaline phosphatase. The paper
      demonstrates the possibility to use in practice the estimation of loop length
      based on the mobility of backbone dihedral angles during molecular dynamics
      simulation. Indeed, it looks that the proteins with new features can be
      constructed by the introduction of new polypeptides into the enzymatically active
      proteins.

PMID- 23113356
TI  - [Sequence-specificity of protein-oligonucleotide interactions and development for
      protein isolation using sorptive medium with immobilized protein-specific
      oligonucleotides].
AB  - Sequence-specificity of binding of ribonuclease binase to
      oligodeoxyribonucleotides immobilized in biochip gel pads was studied. Binding
      constants for the complexes between binase and selected oligonucleotides were
      measured. Oligodeoxyribonucleotides GAGAGAG and GAGAGAGAG were found to be high
      specific in interaction with binase. These oligonucleotides were used as
      molecular probes for immobilization in a sorptive medium for subsequent isolation
      and concentrating of binase from diluted water solutions. Volume capacity of the
      developed sorptive mediums containing immobilized oligodeoxyribonucleotides
      GAGAGAG and GAGAGAGAG was found to be 2.6 and 2.3 mg of binase per 1 mL of
      sorbate correspondingly. After the procedure of affinity chromatography and
      elution ofbinase from sorptive medium the protein showed the same affinity of
      binding to oligonucleotides as the initial sample.

PMID- 23113357
TI  - [Molecular-biological properties of the rubella virus strains isolated in St.
      Petersburg].
AB  - In the surveillance of rubella in the northwest region of Russia samples of
      nasopharyngeal swabs from 37 patients with rubella, which were treated in the
      442nd district military hospital named after Z.P. Solovyov in autumn 2007 were
      screened for the rubella virus using RK-13 cell line, 22 strains of rubella virus
      were isolated. Gene sequencing of E1 region of rubella virus isolates was carried
      out. Rubella virus strains isolated in St. Petersburg during the 2007 outbreak
      belonged to rubella virus genotype 1E. The morphogenesis of RK-13 cells with
      formation of replication complexes and enveloped virions of rubella virus was
      shown.

PMID- 23113358
TI  - [Identification of the polyketide synthase genes (PKS) in genome of the strain
      Pseudomonas fluorescens 28Bb-06 from the freshwater sponge Baikalospongia
      bacillifera].

PMID- 23113360
TI  - [Individual parameters of general low-frequency magnetic therapy as a possibility
      for improving the clinical efficacy of the combined treatment of patients with
      essential arterial hypertension].
AB  - A new approach is proposed for the choice of low-frequency magnetic therapy on an
      individual basis using the results of analysis of heart rhythm variability. The
      clinical efficiency of low-frequency magnetic therapy incorporated in the
      combined treatment of 65 patients aged between 25 and 45 years with essential
      arterial hypertension was estimated. The statistically significant positive
      effects of the treatment included normalization of blood pressure and
      characteristics of heart rhythm variability as well as resolution of clinical
      symptoms of vegetative dysregulation.

PMID- 23113359
TI  - [Medical applications of ozone for the rehabilitation of the patients presenting
      with chronic bronchitis and arterial hypertension].
AB  - Of paramount importance at the stage of rehabilitative treatment of the patients
      presenting with combined cardiorespiratory pathology are therapeutic measures
      aimed at eliminating the principal components of pathogenesis of a given disease
      and correcting the concomitant immunometabolic disturbances. Our investigations
      have demonstrated that ozone therapy given to the patients with chronic
      bronchitis and hypertension produces lipid-lowering, hypoglycemic and
      fibrinolytic effects. Its combination with anti-hypoxic treatment helps to
      normalize the functioning capabilities of all organs and systems of the body.
      Immunomodulatory effects of ozone therapy is attributable to the disintoxicative
      and anti-hypoxic actions of medical ozone as well as activation of the "lipid
      peroxidation--antioxidant protection" system.

PMID- 23113361
TI  - [The application of electrical stimulation of the skeletal muscles for the
      rehabilitation of the patients presenting with peripheral atherosclerosis].
AB  - The course of electrical stimulation of the muscles of lower extremities in the
      patients with peripheral atherosclerosis resulted in the enhancement of exercise
      tolerance manifested as a significant increase of the six-minute walk distance (p
      = 0.001). In addition, the patients of the study group reported increased force
      and endurance of the muscles of lower extremities (by 38-48% and 69-140%
      respectively) that was absent in the control group. It is concluded that
      electrical stimulation of the muscles of lower extremities should be included in
      the combined rehabilitative treatment of the patients presenting with peripheral
      atherosclerosis.

PMID- 23113362
TI  - [Certain aspects of combined vibration training for the treatment of neurological
      manifestations of osteochondrosis in the lumbar spine region].
AB  - The physical rehabilitation of the patients presenting with neurological
      manifestations of osteochondrosis in the lumbar spine region remains a
      challenging problem due to the high prevalence of this condition. Vibration
      training in the form of graduated vibration impacts was shownto induce muscular
      stimulation, activate metabolic processes by promoting microcirculation,
      stimulate operation of the complex proprioceptive apparatus with a rise in the
      energy level of the gamma-system, and lead to the development of long-term post
      activation alterations in the muscular fibers. These observations give reason to
      consider vibration therapy as a most promising method for the combined treatment
      of a variety of diseases affecting human subjects. We have developed a set of
      exercises for the vibration platform training consisting of three main parts
      (preparative, basic, and concluding components).

PMID- 23113363
TI  - [Rehabilitation of the patients suffering from chronic calculous pyelonephritis].
AB  - The objective of the present study was to develop a new technology for the
      balneotherapeutic treatment of the patients with urolithiasis by means of
      combined application of mineral water, mineral baths (1 therapeutic complex),
      sinusoidal modulated current (SMC-phoresis of nicotinamide), and preparations
      inhibiting urine concrement formation. The overall efficacy of this combined
      balneo-, physio-, radio-, and pharmacotherapy of the patients presenting with
      secondary calculous pyelonephritis amounted to 94% compared with 73.4% using
      balneotherapy alone (p1-2 < 0.05). Summation of positive effects of balneo-,
      physio-, radio-, and pharmacotherapies promoted normalization of the functional
      state of the kidneys and the upper urinary tracts which in its turn contributed
      to the improvement of the patient's quality of life.

PMID- 23113364
TI  - [The influence of physiobalneotherapy on the hormonal status of men suffering
      from obesity].
AB  - The objective of the present work was to study the efficacy of the combined
      treatment of the patients suffering from obesity and erectile dysfunction with
      the use of contrast baths, electrical stimulation, and cryomassage. Dynamics of
      the following anthropometric characteristics was evaluated: bodyweight and
      height, body mass index, waist and hip circumference, waist-to-hip ratio. In
      addition, general clinical studies were carried out including total blood count,
      urinalysis, estimation of lipid and carbohydrate metabolism, blood rheologic
      properties, general hormonal status, and psychological testing. The most
      pronounced statistically significant dynamics of the above characteristics was
      documented in the patients treated with the use of general contrast baths,
      remedial gymnastics, electrical stimulation and cryomassage of the anterior
      abdominal wall.

PMID- 23113365
TI  - [The use of restorative medicine technologies for the rehabilitation of the
      patients presenting with endometriosis of external genitalia].
AB  - This paper reports the results of analysis of the psycho-emotional status and
      pain syndrome in the women presenting with endometriosis of external genitalia
      treated with a combination of hormonal preparations and balneotherapy. A total of
      216 infertile patients were involved in the study. The duration of the
      infertility period varied from 1.5 to 19 years. All the patients underwent
      surgical intervention. The influence of rehabilitative therapy on the
      quantitative vital indices (psycho-emotional adaptation to the social environment
      and pain intensity) was estimated before and after the treatment. The patients
      were divided into 3 groups. Those of group 1 received an oral contraceptive (30
      mcg of ethinylestradiol plus 2 mg dienogest) as a continuous three-cycle course
      (63 tablets) followed by its discontinuation for the 7 day menstrual period and
      the final three-cycle course (total duration of therapy 6 months). The patients
      of group 2 were treated with injections of agonists of gonadotropin releasing
      hormone (GnRH) at a dose of 3.75 mg once every 4 weeks (total duration 6 months).
      In group 3, the injections of GnRH agonists (3.75 mg once every 4 weeks, total
      duration 6 months) were combined with a course of balneotherapy using radon. All
      the three rehabilitative modalities produced a well-apparent positive effect.
      Chronic pelvic pain before treatment was reported by 90,3% of the patients. After
      the treatment, the number of such women in groups 1, 2, and 3 decreased to 20,8%,
      12,5%, and 30,6% respectively Dyspareunia in the pre-treatment period was
      diagnosed in 66,7% of the patients. After treatment, this pathology persisted
      only in 23,6%, 18,1%, and 31,9% of the patients in groups 1, 2, and 3
      respectively. Psycho-emotional disorders before treatment were documented in
      90,3% of the patients compared with 27,8%, 25%, and 30,6% after therapy. It is
      concluded that all the three therapeutic modalities markedly improved health
      conditions of the patients presenting with endometriosis of external genitalia,
      but the combination of GnRH agonists with radon therapy produced the most
      pronounced clinical effect.

PMID- 23113366
TI  - [Physical training for the treatment of children presenting with bronchial
      asthma].
AB  - This paper reports the results of the treatment of 101 children presenting with
      bronchial asthma. The study has demonstrated the pronounced positive effect of
      the combined application of a pulsed low-frequency electrostatic field and
      therapeutic physical training on the dynamics of clinical symptoms of the
      disease. By the end of the treatment period, all the patients reported the
      disappearance of paroxysmal night-time coughing, productive cough, expectoration,
      and attacks of respiratory distress. Auscultation failed to reveal dry,
      whistling, and bubbling rales. Dynamics of the changes of the impaired airway
      patency was estimated from the results of computed pneumotachometry and
      monitoring peak expiratory flow by the peak flowmetric technique. The combined
      application of a pulsed low-frequency electrostatic field and therapeutic
      physical training significantly improved characteristics of the external
      expiratory function (PEF, FEV1, MEFR25, MEFR50--p < 0.02, MEFR75--p < 0.001). In
      the end of therapy, 96.7% of the children had normal parameters of computed
      flowmetry in the absence of a generalized impairment of bronchial patency while
      obstruction at the level of peripheral bronchi persisted only in 3.3% of the
      patients. The increase of PEF based on the results of peak flowmetry averaged
      44.21% (p < 0.001). A rationale has been developed for the application of the
      proposed therapeutic strategy to the treatment of children with bronchial asthma.

PMID- 23113367
TI  - [The influence of different massage techniques on the characteristics of
      biological age in the subjects above the age of 30 years].
AB  - This paper is designed to demonstrate the efficacy of different massage
      modalities used to decrease the biological age in relatively healthy subjects
      between 30 and 69 years of life. The study involved 78 subjects (67 women and 11
      men). Each of them underwent a course of 10 sessions of massage of the collar and
      upper back regions for the prevention of premature ageing and the reduction of
      the biological age. Cryomassage was performed with the use of cryocare packs and
      vacuum massage on the Cerri apparatus (Italy). The control group was comprised of
      the subjects given no treatment. The main characteristics measured before and
      after therapy included biomarkers of ageing and biological age. The results of
      the study indicate that both cryogenic and vacuum massage effectively improves
      certain biomarkers of ageing; namely, such treatment reduces systolic, diastolic,
      and pulse pressure, increase pulmonary vital capacity and breath holding time in
      expiration, improves the sense of equilibrium, self-assessment of health
      condition, and concentration of attention. Taken together, these effects
      contribute to the reduction of the biological age of the subjects and prevent
      their premature ageing to a greater extent than in the untreated persons.

PMID- 23113368
TI  - [The influence of general air cryotherapy on the serum lipid spectrum].
AB  - Analysis of the lipid status and oxidation of serum of blood lipids by free
      radicals was performed in the study involving practically healthy volunteers who
      underwent a course of general air cryotherapy. It was ahown that oxidized and
      modified lipoproteins play an important role in the etiopathogenetic mechanisms
      underlying the development of vasoconstrictive reactions and heat production
      processes in response to the short-term exposure to extremely low temperatures.

PMID- 23113369
TI  - [Age-specific dynamics of mental working capacity in different regimens of
      locomotor activity].
AB  - The present study included a total of 392 practically healthy men aged between 40
      and 79 years differing in the character of routine locomotor activity and the
      training status (from masters of sport of international grade to the subjects who
      had never been engaged in sporting activities). They were divided into 4 groups
      each comprised of subjects ranged by age with a ten-year interval. Their mental
      working capacity was estimated from the results of the correction test. The study
      demonstrated that the subjects characterized by a high level of day-to-day
      locomotor activity have higher indices of attention intensity and information
      processing speed compared with the age-matched ones leading a relatively
      sedentary lifestyle. Moreover, they have better chances to retain the mental
      working capacity up to the age of 70 years.

PMID- 23113370
TI  - [The development of a new marker of the training status in athletes].
AB  - The present study was based on the mathematical modeling of the middle molecular
      weight peptides (MMWP) concentration in the blood. On the one hand, MMWP are the
      products of partial protein catabolism, on the other hand, they act as inductors
      of protein synthesis. We have developed a complex hormonal marker that allows
      estimating the adaptive reactions in the organism of the athletes. The marker
      integrates the known hormonal indices, such as testosterone to cortisol ratio and
      aldosterone to cortisol ratio (-1,271 + 0,206 x 1n(testosterone) + 1,108 x
      1n(aldosterone))/1n(cortisol). The use of a mathematical model for the prediction
      of MMWP levels in the rowers' blood provides a basis for the application of the
      new marker for the evaluation of physical conditions of the high-class athletes
      engaged in other sports. By way of example, the estimation of its informative
      value for the examination of swimmers has demonstrated significant positive
      correlation between the predicted and observed MMWP levels (r = 0,4187; p =
      0,050). Practicability of applying the newly proposed hormonal marker for
      monitoring adaptative reactions in athletes is confirmed by significant
      correlation of calculated values with the real time the freestyle swimmers spend
      to cover a 50 m distance (r = - 0,4454; p = 0,001).

PMID- 23113371
TI  - [Physical education and training in the system of purpose-oriented health
      promotion at the stage of medical rehabilitation].
AB  - The present article concerns organization of the health promotion system and its
      practical implementation with a view to making healthier the population of Russia
      in general.

PMID- 23113372
TI  - [Peloid therapy: the theoretical and practical aspects, problems and prospects of
      its development].
AB  - The present literature review contains the data on the history of peloid therapy,
      current concepts of the mechanisms of its action, and up-to-date methods of
      peloid applications. Special emphasis is laid on the lack of relevant information
      concerning selected aspects of peloid therapy, debatable views of its application
      and mechanisms of action. The review is concluded by the discussion of the
      prospects for further research and practical use of peloid therapy.

PMID- 23113373
TI  - 3D numerical study of tumor microenvironmental flow in response to vascular
      disrupting treatments.
AB  - The effects of vascular-disrupting treatments on normalization of tumor
      microvasculature and its microenvironmental flow were investigated, by
      mathematical modeling and numerical simulation of tumor vascular-disrupting and
      tumor haemodynamics. Four disrupting approaches were designed according to the
      abnormal characteristics of tumor microvasculature compared with the normal one.
      The results predict that the vascular-disrupting therapies could improve tumor
      microenvironment, eliminate drug barrier and inhibit metastasis of tumor cells to
      some extent. Disrupting certain types of vessels may get better effects. In this
      study, the flow condition on the networks with "vascular-disrupting according to
      flowrate" is the best comparing with the other three groups, and disrupting
      vessels of lower maturity could effectively enhance fluid transport across
      vasculature into interstitial space.

PMID- 23113374
TI  - Computational study of stented and wrapped aortic aneurysms.
AB  - Aortic aneurysm is a pathology that involves the enlargement of the aortic
      diameter and has risk factors including aortic dissection. Aneurysm wrapping and
      stent placement has been used in the treatment of aneurysms. This study aimed to
      investigate the biomechanical effects of wrapping and stenting on aneurysm. The
      three-layered aortic aneurysm were created and fluid structure interaction were
      simulated in wrapped model and stented model. The results provide quantitative
      predictions of flow patterns and wall mechanics as well as the effects of
      wrapping and stenting.

PMID- 23113375
TI  - Cellular automata modeling of pulmonary inflammation.
AB  - Better understanding of the acute/chronic inflammation in airways is very
      important in order to avoid lung injuries for patients undergoing mechanical
      ventilation for treatment of respiratory problems. Local lung inflammation is
      triggered by many mechanisms within the lung, including pathogens. In this study,
      a cellular automata based model (CA) for pulmonary inflammation that incorporates
      biophysical processes during inflammatory responses was developed. The developed
      CA results in three possible outcomes related to homeostasis (healing),
      persistent infection, and resolved infection with high inflammation (inflamed
      state). The results from the model are validated qualitatively against other
      existing computational models. A sensitivity analysis was conducted on the model
      parameters and the outcomes were assessed. Overall, the model results showed
      possible outcomes that have been seen in clinical practice and animal models. The
      present model can be extended to include inflammation resulting from damage
      tissue and eventually to model inflammation resulting from acute lung injury and
      multiple organ dysfunction syndromes in critical illness and injury.

PMID- 23113376
TI  - Effect of age-stiffening tissues and intraocular pressure on optic nerve damages.
AB  - Age-stiffening of ocular tissues is statistically linked to glaucoma in the
      elderly. In this study, the effects of age-stiffening on the lamina cribrosa, the
      primary site of glaucomatous nerve damages, were modeled using computational
      finite element analysis. We showed that glaucomatous nerve damages and peripheral
      vision loss behavior can be phenomenologically modeled by shear-based damage
      criterion. Using this damage criterion, the potential vision loss for 30 years
      old with mild hypertension of 25 mmHg intraocular pressure (IOP) was estimated to
      be 4%. When the IOP was elevated to 35 mmHg, the potential vision loss rose to
      45%; and age-stiffening from 35 to 60 years old increased the potential vision
      loss to 52%. These results showed that while IOP plays a central role in
      glaucomatous damages, age-stiffening facilitates glaucomatous damages and may be
      the principal factor that resulted in a higher rate of glaucoma in the elderly
      than the general population.

PMID- 23113377
TI  - A pilot cost-of-illness study on long-term complications/sequelae of AOM.
AB  - OBJECTIVES: Acute otitis media (AOM) commonly affects young children and
      occasionally results in serious complications/sequelae. This pilot cost-of
      illness study aimed to assess the economic burden of long-term AOM
      complications/sequelae in Belgium, and to establish a thorough methodology for a
      larger study. METHODOLOGY: We retrospectively reviewed charts of patients aged 10
      20 years with long-term complications/sequelae considered to be AOM-related, and
      > or = 8 years of follow-up. From a list of 215 eligible patients, we selected 25
      patients representing each of seven categories of complications/sequelae.
      RESULTS: Included patients had a mean age of 12.9 years; nine had chronic
      suppurative otitis media with cholesteatoma; six sensorineural hearing loss; six
      chronic perforation of the tympanic membrane; and one each with conductive
      hearing loss, facial paralysis, neurological impairment after intracranial
      complications, and complications of surgery. During 8-15 years of follow-up, the
      most common complications were hearing loss, chronic otitis media (OM), and
      cholesteatoma. These generally occurred > 5 years after the first AOM event,
      although chronic OM occurred after a mean time of 3.3 years. Yearly public health
      care payer (PHCP) costs ranged from Euro 119 to Euro 7957 per patient, and were
      highest for patients with sensorineural hearing loss. Yearly costs to the
      patients ranged from Euro 7 to Euro 289 per patient, and were also highest for
      patients with sensorineural hearing loss. CONCLUSIONS: Although
      complications/sequelae of AOM are rare, they can result in substantial costs. The
      applied methodology should be feasible for a larger study, with some minor
      adjustments.

PMID- 23113378
TI  - Tinnitus and quality of life following vestibular schwannoma surgery.
AB  - OBJECTIVE: This study on patients undergoing surgery for vestibular schwannoma
      investigated tumour (i) the effect of pre-operative factors on tinnitus, (ii) the
      effect of translabyrinthine or hearing preservation surgical approaches on
      tinnitus, and (iii) the effect of postoperative tinnitus status on the patient's
      quality of life (QOL). METHODOLOGY: Seventy-nine patients who underwent
      vestibular schwannoma (VS) excision between 2001 and 2005 were selected.
      Postoperative tinnitus status was evaluated using a standard questionnaire for
      tinnitus, and QOL was measured using the Glasgow Benefit Inventory (GBI).
      RESULTS: Overall, 58% of patients noted tinnitus before tumour removal. Pre
      operative tinnitus was not associated with age, gender, tumour size, or hearing
      thresholds. The total percentage of patients suffering postoperative tinnitus was
      64%. Hearing preservation approaches showed no difference in terms of changes in
      tinnitus compared to the translabyrinthine approach. Twenty-one patients (30%)
      reported better QOL, 40 patients (56%) reported worse QOL, and 10 patients (14%)
      reported the same QOL. A significant association was found between tinnitus
      worsening as measured by GBI score and QOL. CONCLUSIONS: Most patients do not
      report significant changes in their tinnitus status after surgery. Tinnitus
      evolution is unpredictable and not related to the type of surgical approach.
      Thus, tinnitus should not be used as a criterion for selecting the surgical
      approach. Tinnitus worsening appears to influence QOL following surgery for VS.

PMID- 23113379
TI  - Profound sensorineural hearing loss: analysis of 310 adult cases.
AB  - OBJECTIVES: Sensorineural hearing loss is caused by problems in the inner ear,
      vestibulocochlear nerve, or brain central processing centers. This study aimed to
      analyze the patient-reported etiology, clinical aspects, and hearing evolution of
      patients with profound sensorineural hearing loss (PSNHL). STUDY DESIGN:
      Retrospective. METHODS: A total of 310 adult patients diagnosed with PSNHL in one
      or both ears between January 2002 and January 2008 were studied at a secondary
      center. Most subjects were military-aged males who were diagnosed with PSNHL
      during routine examinations prior to recruitment. A pure-tone audiometry test was
      performed in all patients. Auditory brainstem response was recorded in 142
      (45.8%) patients. RESULTS: A total of 310 adult patients (276 males [89%] and 34
      females [11%]) with a mean age of 23.1 (range 20-81) years comprising 486 ears
      consisting of 176 (56.8%) bilateral and 134 (43.2%) unilateral PSNHL cases were
      evaluated. Etiology was based on patient self reporting. The disease was
      congenital in 93 (30%) patients and acquired in 217 (70%). Etiology was unknown
      in 35 (11.3%) patients. Acquired hearing losses were rapid in 188 (86.6%) and
      progressive in 29 (13.4%) patients. Articulation was impaired (no understandable
      speech) in a total of 146 patients (47.1%), including all patients with
      congenital PSNHL. CONCLUSION: The cause of hearing loss is often understood from
      medical history. Taking measures for the most common causes (congenital hearing
      loss and childhood infectious diseases) may reduce occurrences of PSNHL cases.
      Auditory screening and beginning hearing rehabilitation as soon as possible in
      newborns is vital.

PMID- 23113380
TI  - Methodologic assessment after functional endoscopic sinus surgery.
AB  - OBJECTIVES: Functional endoscopic sinus surgery (FESS) has become the procedure
      of choice to treat chronic rhinosinusitis. However, no standard method has been
      suggested to measure FESS outcome. In this study, we used different methods to
      measure FESS outcome, to determine which method was the most accurate. METHODS:
      Forty-nine patients with chronic rhinosinusitis who underwent FESS were enrolled
      in this study. Nasal polyps were present in 27 patients. On the day before FESS
      and 12 weeks after the procedure, all patients filled out a Chinese-language
      version of the 31-item Rhinosinusitis Outcome Measure (CRSOM-31) and received
      acoustic rhinometry to measure the second minimal cross-sectional area (MCA2) of
      the nasal cavity, as well as an endoscopic examination and a computed tomography
      (CT) scan. RESULTS: When CRSOM-31, MCA2, endoscopy, and CT scores were analyzed,
      a good correlation was observed between preoperative endoscopy and CT scores in
      patients with or without nasal polyposis (r = 0.459, p = 0.016; r = 0.578, p =
      0.005, respectively). Postoperatively, a good correlation was observed between
      CRSOM-31 and CT scores in patients with nasal polyposis (r = 0.405, p = 0.036),
      as well as between CRSOM-31 and endoscopy scores in patients without nasal
      polyposis (r = 0.64, p = 0.001). CONCLUSIONS: Our results showed that it is
      difficult to choose a method with which to measure FESS outcome accurately.
      However, a longer follow-up time and more patients are needed to justify these
      short-term postoperative results.

PMID- 23113381
TI  - Anatomical variations in sinus imaging in sinusitis: a case control study.
AB  - OBJECTIVE: To compare anatomical variations in sinusitis patients and control
      subjects. SUBJECTS AND METHODS: We reviewed and compared the computed tomography
      (CT) scans of 87 sinusitis patients after adequate medical treatment and scans of
      103 healthy subjects. All images were scored for sinusitis severity using the
      Lund-Mackay scoring system. Anatomical variations such as septal deviation,
      concha bullosa, presence of the Haller's cell, paradoxical middle turbinate,
      prominent agger nasi cell, and Onodi cell were also recorded. RESULTS: Of the 190
      evaluated CT images, 55.2% of the cases and 47.6% of the controls had septal
      deviation (p > 0.05). The prevalence of concha bullosa was 68% in patients and
      61% in controls (p > 0.05). CONCLUSION: There were no significant differences in
      the evaluated anatomical variations between cases and controls in this study.
      Mucosal inflammation may play a more essential role than anatomical variation in
      the development of sinusitis.

PMID- 23113382
TI  - Development of a tool for Global Rating of Endoscopic Surgical Skills (GRESS) for
      assessment of otolaryngology residents.
AB  - OBJECTIVE: To develop a valid and reliable assessment tool for endoscopic sinus
      surgery (ESS). MATERIAL AND METHODS: Data were collected prospectively in an
      observational study through evaluations at two tertiary academic institutions,
      i.e. St. Paul's Sinus Centre, St. Paul's Hospital, Vancouver, British Columbia,
      Canada, and King Fahd Medical City, Riyadh, Saudi Arabia, from December 2006 to
      December 2009. A 2-page evaluation form was developed in conjunction with the
      Objective Assessment of Technical Skills Surgery (OSATS) evaluation form
      developed by Reznick et al in Toronto to assess residents' surgical skills. A
      Likert scale (1-5 where 5 = excellent) was used for evaluations. The Global
      Rating of Endoscopic Surgical Skills (GRESS) evaluation instrument was designed
      with input from academic otolaryngologists, fellowship-trained rhinologists, and
      experts in medical education. The experts' comments were incorporated,
      establishing face and content validity. Residents from various levels of training
      were assessed objectively using this instrument. Internal consistency was
      evaluated using Cronbach's alpha. Test-retest and inter-rater reliability was
      measured using intra-class correlation. RESULTS: A total of 31 assessments were
      completed by 15 residents. GRESS showed high reliability in the context of
      internal consistency (alpha = 0.99), test-retest (0.95, CI = 0.83-0.98), and
      inter-rater reliability (0.86, CI = 0.31-0.98). CONCLUSIONS: This pilot study
      demonstrated that GRESS is a valid and reliable assessment tool for operating
      room performance.

PMID- 23113383
TI  - Intralesional cidofovir in severe juvenile respiratory papillomatosis.
AB  - Recurrent respiratory papillomatosis causes significant morbidity among affected
      children and usually requires frequent surgeries. We present a prospective case
      series including nine children at a Mexican tertiary referral center. All
      enrolled patients had severe disease that had required at least four surgical
      procedures, with a median of 6. Two children had tracheobronchial involvement,
      one had lung parenchymal disease, and one had a tracheostomy performed during his
      first surgery. OBJECTIVE: To assess the efficacy of intralesional cidofovir in
      lowering the surgery rate. STUDY DESIGN: Prospective case series. SETTING:
      Tertiary referral center in Mexico City. METHODS: Nine Mexican children with
      severe disease were enrolled. Intralesional cidofovir was applied after surgical
      debulking at a concentration of 5 mg/mL with a four to six week interval.
      RESULTS: Six of the nine patients had a notable decrease in the rate of
      surgeries, with three patients remaining disease-free with follow up ranging from
      1.8 to 3.3 years. No patient demonstrated laboratory abnormalities. Two patients
      showed moderate and mild dysplasia on papilloma biopsy distinguished by a lack of
      epithelial maturation with no mitoses or cellular atypia. Two patients died
      several months after the last injection. CONCLUSIONS: Intralesional cidofovir
      appears to be effective in the treatment of recurrent respiratory papillomatosis,
      although further studies are required to determine its safety.

PMID- 23113384
TI  - Tension pneumocephalus: a life-threatening complication of septoplasty and
      septorhinoplasty.
AB  - PROBLEMS/ OBJECTIVES: Septoplasty and septorhinoplasty are two important surgical
      operations in otorhinolaryngology. Tension pneumocephalus is a rare, but
      potentially fatal, intracranial complication of these operations. METHODOLOGY: We
      present two cases of tension pneumocephalus following nasal surgery. Both
      patients had tension pneumocephalus, meningitis, and defects in the skull base.
      RESULTS: One patient underwent endoscopic repair of the defect, while the second
      case expired despite medical and neurosurgical management.

PMID- 23113385
TI  - Transnasal endoscopic resection of vidian nerve schwannoma accompanied by
      sphenoid mucopyocele and oculomotor palsy: a case report.
AB  - Schwannomas are rare tumours arising from the peripheral nerve sheath. Nearly
      half of all schwannomas occur in the head and neck region, but the sinonasal
      tract is rarely involved. We report on an extremely rare case of vidian nerve
      schwannoma accompanied by mucopyocele with symptoms of oculomotor palsy and CSF
      leakage. An exclusively endoscopic endonasal approach was performed to excise the
      tumour and the dural defect was repaired. To our knowledge, this is the first
      time a vidian nerve schwannoma has been excised in an exclusively endoscopic
      approach. We first review the literature and then discuss the benefits for
      patients undergoing this type of operation.

PMID- 23113386
TI  - Leiomyosarcoma of the inferior nasal concha: a case report and literature review.
AB  - Leiomyosarcomas (LMSs) of the sinonasal tracts are rarely reported. We present a
      case of an LMS of the left inferior nasal concha, and discuss the management
      options with review of the literature. A 72-year-old female patient presented
      with epistaxis. Clinical examination and medical imaging showed a tumour arising
      from the left inferior nasal concha. An endoscopic resection was performed.
      Anatomopathological and immunohistochemical analyses revealed the tumour to be a
      grade 3 LMS with uncertain posterior margins. The patient was a Jehovah's Witness
      and refused more radical surgical resection due to religious beliefs; therefore,
      adjuvant conformal radiotherapy (60 Gy) was performed. LMS of the nasal cavity is
      a rare and locally aggressive tumour with a high tendency of recurrence,
      requiring radical surgical resection and long-term follow-up. The prognosis of a
      nasal cavity LMS is better than that of an LMS located in the paranasal sinuses.

PMID- 23113387
TI  - Solitary fibrous tumour of the nasal cavity: a case report and literature review.
AB  - A solitary fibrous tumour (SFT) is a rare tumour that originates from the
      mesenchyme and arises mainly in the pleura. In this report, we present a rare
      case of a 77-year-old man with a SFT in the left nasal cavity. On CT and MRI, a
      large mass is seen in the left nasal cavity, extending to the choana. The mass
      was radically resected via functional endoscopic sinus surgery (FESS).
      Histological examination showed a fibroblastic mesenchymal tumour with a
      prominent hemangiopericytic vascular branching pattern that stained diffusely
      positive for the immunohistochemical markers CD34, Bcl-2, and CD99, which was
      compatible with the histopathological diagnosis of a SFT. Imaging and
      histological features are discussed, along with the reports in literature,
      clinical management, and follow-up of this pathology.

PMID- 23113388
TI  - Intraparotid facial nerve schwannoma: case report and literature review.
AB  - A 68-year-old female presented with a right parotid mass and partial frontal
      peripheral facial nerve palsy. Pre-operatively, the mass was thought to be
      benign. Surgical intervention consisted of parotidectomy with sacrifice of the
      facial nerve due to the nerve's involvement in the tumoural process and its
      intrapetrosal course. Immediate nerve reconstruction was performed by an
      interposition graft of the great auricular nerve. Pathological examination
      revealed a schwannoma of the facial nerve. Review of the literature on this rare
      parotid gland tumour is reported.

PMID- 23113389
TI  - Carmine red (E-120)-induced occupational respiratory allergy in a screen-printing
      worker: a case report.
AB  - Here we present a case report of a patient suffering from occupational
      rhinoconjunctivitis and asthma due to IgE-mediated carmine red allergy. This is
      the first description of carmine red allergy in a screen-printing worker in which
      the diagnosis was documented by quantification of specific IgE antibodies, by
      skin tests, by a flow-assisted basophil activation test, and by a carmine red
      challenge test.

PMID- 23113390
TI  - [Conservative management of retained central venous catheters].
AB  - BACKGROUND: Withdrawal of central venous catheters (CVCs) is usually a simple
      surgical procedure. However, in some cases, the catheter is stuck in the vessel
      wall and its removal is not possible if more invasive interventions are not
      performed. MATERIAL AND METHODS: We performed a retrospective study from 2003 to
      2011 of patients who were clearing a CVC and the factors that could have
      intervened in the removal impossibility. We compared the type of catheter, the
      insertion site, the time between its insertion and removal, the primary diagnosis
      and the treatment. In addition, a monitoring by clinical and imaging tests has
      been made in patients with retained CVCs. RESULTS: An amount of 174 interventions
      were carried out. In 5 cases the CVC could not been removed. These 5 cases were
      patients diagnosed with ALL B and were treated with identical chemotherapy
      treatment. In addition, at the time of its retirement, all the patients had the
      CVC for a period longer than 2 years -29 to 84 months-. In patients with retained
      fragments, no complication arose from this condition. The mean follow-up period
      was 36 months -maximum 48 months-. CONCLUSIONS: The potential complications
      arising from the presence of the retained CVCs fragments include infection,
      venous thrombosis and catheter migration. Based on our results, we propose that a
      conservative management might be considered as an option in these patients.

PMID- 23113391
TI  - [Modifiable prognostic factors in the morbidity-mortality of gastroschisis].
AB  - OBJECTIVE: The low incidence of gastroschisis makes impossible a consistently
      study of the factors that determine its evolution. The presence of other
      alterations associated is an important determinant of prognosis known. We analyze
      the factors implicated in morbidity and mortality in our center that can be
      modified. MATERIAL AND METHODS: We performed a retrospective study from hospital
      records. We analyzed the morbidity and mortality versus gestational age, mode of
      delivery, surgery performed, presence of prenatal diagnosis, herniated viscera
      and associated anomalies. We studied the postoperative differences occurred as a
      result of implantation of fetal surgery group. The variables were analyzed with
      SPSS 15.0 using non-parametric test. RESULTS: Since 1987 25 patients have been
      operated (12 men) with a mean birth weight of 2,328 g +/- 364. The 44% of them
      had prenatal diagnosis and 72% were born by cesarean. Only 4 had intestinal
      atresia. Preterm birth (< 36 weeks) did not improve the complications, but did
      reduce hospital stay in 10.68 days and the time of parenteral nutrition in 6
      days. Cesarean delivery and prenatal diagnosis was improved all the previous
      factors. Primary closure however was associated with higher rates of postsurgical
      complications (46.2% vs. 18.2%). The 5 patients who died was during the immediate
      postoperative period, all before developing the fetal diagnostic program.
      CONCLUSIONS: Prenatal diagnosis and preterm delivery by elective cesarean reduces
      the complications of gastroschisis. Interdisciplinary coordination is essential
      to improve the prognosis of these patients.

PMID- 23113393
TI  - [Cross-sectional study of deviated nasal septum in unilaterally operated
      fissures].
AB  - INTRODUCTION: Nasal septum deviation is one the most significant nasal
      deformities among cleft and lip patients and its anatomical variations along the
      anterior-posterior axis within the nasal cavity has not been specified. AIM: To
      define whether there are differences in the degree of nasal septum deviation
      between the anterior, middle and posterior areas of the nasal cavity in operated
      unilateral cleft lip and palate patients. MATERIAL AND METHOD: Twenty-nine
      unilateral complete cleft lip and palate patients, between 5 and 17 years,
      attending San Borja Arriaran Hospital and the University of Chile's School of
      Dentistry were included. The nasal septum deviation index was measured at
      different depths across the anteroposterior axis by cone-beam computed
      tomography. A random effects model was performed for data analysis. RESULTS: The
      nasal septum deviation index presented differences between the three planes
      studied. The plane with lesser deviation was the anterior, while the plane with
      greater deviation was the posterior. These differences resulted statistically
      significant (P < 0.05). CONCLUSION: In complete unilateral cleft and lip patients
      mainly the posterior part of the nasal septum should be corrected, because there
      is a greater deviation in that area.

PMID- 23113394
TI  - [Fertility survey of patients operated on of cryptorchidism in the pediatric
      age].
AB  - OBJECTIVES: To analyze the fertility survey made in a cohort of adults operated
      on as children for cryptorchidism and for whom clinical and surgical data is
      available and who were studied 10 years ago by spermiogram and hypophyseal axis.
      METHODS: A fertility survey including data on style of life and work conditions
      was sent to the homes of 278 adult patients operated on for cryptorchidism. The
      94 surveys received (33.8% of those sent) were analyzed using the SPSS 15.0,
      carrying out a descriptive and analytic study. We consider persons who achieve
      pregnancy within a maximum of 12 months with regular sexual activity without the
      use of contraceptives as having normal fertility. RESULTS: A total of 53 cases of
      those surveyed (56.4%) attempted to have children, 44 (83.1%) being successful. A
      total of 34 patients (64.2%) were considered fertile with a mean time of 4.15
      months to become pregnant. Nineteen patients (35.8%) had attempted to become
      parents for more than 12 months and only 10 achieved it (18.9%), 5% in a natural
      way, 2 with ovulation treatment and 3 by in vitro fertilization, with a mean of
      26.8 months. There was no success in becoming parents in 9 cases (16.9%). There
      are no significant differences between fertilization and localization in
      laterality of the testicle, age at time of surgery and density on spermiogram.
      There are significant differences between natural paternity and unilateral or
      bilateral cryptorchidia. CONCLUSIONS: There is a greater proportion of unilateral
      cryptorchidias in the group that was successful in having children. We need to
      increase the number of those surveyed in order to draw significant conclusions in
      regards to fertility and other clinical situations.

PMID- 23113392
TI  - [Neonatal extracorporeal membrane oxygenation: 9 years of experience].
AB  - INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) is a rescue therapy for
      reversible respiratory or cardiac diseases. Neonatal pathologies requiring this
      technique are different from the ones found later in life. OBJECTIVES: To review
      the main causes requiring ECMO in the neonatal period, to compare the clinical
      course depending on the initial illness and to identify the sequelae attributable
      to this technique. MATERIAL AND METHOD: A retrospective review of clinical
      records of all neonatal patients that received ECMO support in our centre.
      RESULTS: 45 neonatal ECMO were performed in our unit between January 2001 and
      June 2009. Forty techniques were due to respiratory failure, 2 secondary to
      haemodynamic shock and 3 secondary to sepsis. Veno-venous cannulation was used
      initially in 24 patients (53.3%). The length of technique varied depending on the
      underlying disease. Patients with congenital diaphragmatic hernia were in ECMO
      for longer periods. The overall survival to the technique was 86.3% (38/44
      patients), also with differences among diseases. Extracorporeal support was
      withdrawn in 4 children because of a diagnosis of an irreversible pathology and
      one because of massive brain haemorrhage. No serious adverse outcomes
      attributable to the technique were found among survivors. CONCLUSIONS: Survival
      among newborns supported with ECMO in our hospital is similar to that recorded by
      the ELSO in 2004, although we use veno-venous cannulation in more than a half of
      the patients. The percentage of moderate to severely impaired neurodevelopmental
      outcome among survivors after this technique was low.

PMID- 23113395
TI  - [Evaluation of quality of life in patients operated on for gastroesophageal
      reflux in the pediatric age].
AB  - AIM: To assess the quality of life and symptoms of GER patients who underwent
      laparoscopy in our hospital before and after surgery. MATERIAL AND METHODS: We
      collect data from patients operated laparoscopically for gastroesophageal reflux
      disease (GER) in our center before and after surgery in 3 items: nutritional
      studies, diagnostic methods, interviews with the families of patients about
      symptoms (preferably differing in digestive or respiratory symptoms) and quality
      of life; also, determined the age, gender, personal history and surgical
      technique of patients. RESULTS: 30 patients have been operated for GER, 22 men
      and 8 women, 11 months to 14 years (median age 5 years) of whom 12 (40%) had some
      degree of encephalopathy. The most common surgical technique used is Nissen (73%
      cases). Most patients had significant alterations in their daily activities
      before surgery. The most common symptom was gastrointestinal (70% cases),
      although all showed improvement, families of children with respiratory symptoms
      related predominantly greater reduction in the clinic after surgical correction.
      All improved in its growth curve. CONCLUSIONS: Surgery for GER patients have a
      significant improvement in their quality of life, not only by the reduction of
      their symptoms but also in enhancing from the nutritional status. Patients with
      respiratory symptoms have a higher satisfaction with surgical treatment than
      those with gastrointestinal clinical.

PMID- 23113396
TI  - [Hirschsprung's disease and medullary carcinoma of the thyroids: two diseases in
      a monogenetic disorder].
AB  - INTRODUCTION: The most common gene involved in Hirschsprung's disease (HD) is
      protooncogene RET. More than 100 mutations of this gene have been described
      associated with HD. The mutations that change a cysteine with another aminoacid
      (mainly in exons 10 and 11) give a risk of familial medullary thyroid carcinoma
      (FTMC) and MEN 2A. These mutations are found in 5% of patients with HD and have
      an autosomal dominant inheritance. The FTMC is aggressive and the prophylactic
      thyroidectomy is the best treatment. We present our results in screening for RET
      protooncogene mutations associated with TMC in patients with HD. PATIENTS AND
      METHODS: We have treated 40 patients with HD in the last 15 years. We have
      classified the patients into two groups: A) high risk of RET protooncogene
      mutation associated with FTMC (family history of HD, long-segment and/or
      associated syndromes) and B) low risk (rectosigmoid involvement). We have
      identified the exons 7, 8, 9, 10, 11, 13, 14 and 15 of the RET protooncogene in
      12 of 15 children from group A and 6 from 25 from group B. RESULTS: We have found
      the p.Cys620Ser mutation (exon 10) in a girl from group A (long-segment). In the
      family study, we have found the same mutation in her mother, her oncle and her
      cousin. CONCLUSION: The comprehensive management of children with HD requires
      screening for RET protooncogene mutations associated with FTMC. In the first
      degree relatives of children with a mutation risk, screening is required.

PMID- 23113397
TI  - [Pediatric surgery 2.0].
AB  - New tools from the web are a complete breakthrough in management of information.
      The aim of this paper is to present different resources in a friendly way, with
      apps and examples in the different phases of the knowledge management for the
      paediatric surgeon: search, filter, reception, classification, sharing,
      collaborative work and publication. We are assisting to a real revolution on how
      to manage knowledge and information. The main charateristics are: immediateness,
      social component, growing interaction, and easiness. Every physician has clinical
      questions and the Internet gives us more and more resources to make searchs
      easier. Along with them we need electronic resources to filter information of
      quality and to make easier transfer of knowledge to clinical practice. Cloud
      computing is on continuous development and makes possible sharing information
      with differents users and computers. The main feature of the apps from the
      Intenet is the social component, that makes possible interaction, sharing and
      collaborative work.

PMID- 23113398
TI  - [Burns in adolescents].
AB  - INTRODUCTION: The aim of this study was to know the epidemiology of burns in
      teenagers. PATIENTS AND METHODS: Burn patients over 11 years old admitted in our
      Institution in the last 10 years were included. Etiology, burn size, hospital
      stay, quirurgical interventions and long term sequelae were registered. RESULTS:
      One thousand and eight patients were admitted, 89 were over 11 years (8.8%),
      70.7% were boys and 29.3% girls. Fire was the principal agent in 58 cases
      (65.1%), due to fireworks in 13 (22.4%), alcohol in 7 (12%), explosion of
      flammable containers (spray) in 4 (6.8%) and gasoline in 3 (5.2%). Fireworks
      injuries and spray explosions affected face and hand in 88% cases. The median
      hospital stay was 8 days after admission (1 to 90). 83.1% required surgical
      treatment with mean of 1.8 +/- 1.4 interventions and 21.3% had long-term
      sequelaes that required at least one surgical intervention. CONCLUSION: Fire is
      the main cause of burns in adolescents. Fireworks injuries represented a quarter
      of that lesions, and highlights paint spray explosions as new causative agents.
      Considering the high morbidity in this age group, with permanent functional and
      aesthetic sequelae, prevention campaigns are needed to reduce such accidents.

PMID- 23113399
TI  - [Technical aspects of experimental intestinal transplant].
AB  - PURPOSE: Our objective is to analyze the variables that influence the outcome of
      Small Bowel Transplantation (SBT) in rats in an experimental microsurgery
      program. The surgical technique and perioperative care are described in detail.
      METHODS: Retrospective study of the SBT in rats conducted in our experimental
      surgery laboratory from 2002 to 2010. The animals were divided into group A
      (those who survived more than 48 hours) and group B (those who died earlier
      without justificable cause). We compared in both groups: number of transplants
      performed by the surgeon, warm ischemia time, cold ischemia time and duration of
      the procedure. RESULTS: Five surgeons with different degrees of microsurgical
      training participated in the study. A total of 521 SBT were performed with an
      overall survival of 48%. The first successful transplant was performed after a
      median of 46 (25-68) transplants. Total procedure time (3.5 vs 2.9 hours) and
      warm ischemia time (51 vs 35 minutes) were higher in group B (p < 0.05).
      DISCUSSION: The number of transplants required for learning the technique is
      high. However, survival is acceptable when the time needed for vascular
      anastomosis is reduced. The SBT in rats is a valuable model for surgical training
      and research of the phenomena related to SBT.

PMID- 23113400
TI  - [Presurgical nasoalveolar molding a child with cleft lip and palate].
AB  - The cleft lip and palate are among the diseases that benefit most from the
      creation of multidisciplinary units (paediatric surgeons, maxillofacial and
      plastic, orthodontist, otolaryngologist, speech therapist, psychologist, etc.).
      The objectives of presurgical orthodontic and orthopedic treatment are: 1.--Align
      the alveolar segments and reduce the width of the cleft to facilitate
      cheiloplasty. 2.--To guide the growth of the segments in which the jaw is
      divided. 3.--Improve lingual function. 4.--Shaping the nasal cartilage and the
      columella. We review developments in the treatment results in presurgical NAM
      (PNAME) in 15 patients treated in cleft lip and palate Unit Hospital Virgen de
      las Nieves (10 unilateral and 5 bilateral). Three patients did not complete
      treatment because of lack of cooperation from parents who dropped by the baby's
      crying. In all patients who completed a significant improvement was achieved in
      the alignment and spacing of the alveolar segments and in the shape of the alar
      cartilage. The learning curve in shaping makes each time the results are better
      and communication between parents of patients causes dropouts are virtually zero.

PMID- 23113401
TI  - [Early reconstruction of congenital pseudoarthrosis of the tibia with free
      vascularized fibular grafts].
AB  - Congenital pseudoarthrosis of the tibia (CPT) is an uncommon disease presenting a
      tibial nonunion since birth and frequently associated to neurofibromatosis type
      1. Surgical management by wide excision of the pseudoarthrosis and sustitution of
      the defect with vascularized bone in an early stage has proven to be the most
      effective technique in terms of bone consolidation. We present a clinical case of
      a 22-month-old patient with CPT treated successfully by reconstruction with a
      free vascularized fibula graft with an excellent functional result.

PMID- 23113402
TI  - [Intranodal myofibroblastoma: a case report].
AB  - INTRODUCTION: Myofibroblastomas are part of the heterogeneous group of
      myofibroblastic tumours, having first been described in 1989. They may be
      malignant or present a benign behaviour. Clinically they appear as a painless
      progressively growing mass in the soft tissue. CASE REPORT: A 12-year-old female
      teenager was referred to our hospital with a 1-year history of a painless growing
      mass in the inguinal region. A surgical excision was performed; its histological
      study revealed a proliferation of spindle cells arrayed in a fascicular pattern
      and with nuclear palisading, occupying the lymph nodes. Immunohistochemichal
      analysis demonstrated reactivity for vimentin, focally positive for CD34 and
      smooth muscle actin. She was then diagnosed with intranodal myofibroblastoma. Two
      years after the surgical excision there was a local recurrence followed by
      another resection. There have been no new recurrences 3 years after the second
      intervention. CONCLUSION: The intranodal myofibroblastoma is a rare benign
      mesenchymal neoplasm, without known pediatric cases and presenting differential
      diagnosis with other soft tissue tumours. Immunohistochemical studies are
      essential to establish its myofibroblastic nature.

PMID- 23113403
TI  - [Fetal surgery of myelomeningocele: from experimental results to clinical
      evidence].

PMID- 23113404
TI  - [Laparoscopic assisted percutaneous treatment of inguinal hernia in infants].
AB  - INTRODUCTION: Thanks to the generalization of minimally invasive surgery in
      pediatric patients some classic techniques are being replaced. Inguinal hernia
      repair may be an example. MATERIAL AND METHODS: We present the technique and our
      first results in 10 patients treated by percutaneous laparoscopic assisted
      herniotomy. For this purpose we used an umbilical port, for a 5 mm camera and an
      optional 2 mm grasper. By laparoscopic guidance we make two inguinal punctures
      with a 20G needle that introduces a non absorbable suture that crosses the whole
      inguinal defect and allows it closure by extracorporeal knot tying. RESULTS: The
      ages ranged between 1 month and 8 years with a median age of 10 months. 50% of
      the patients were boys. 50% of the patients had previous diagnosis of inguinal
      bilateral hernia. 30% of patients presented a postoperatory diagnosis different
      from the previous one. The average time of intervention was 32 minutes in
      bilateral hernias, and 19 in the unilateral ones. Follow-up time was 6 months
      without complications. The aesthetic result was ideal. CONCLUSION: Percutaneous
      laparoscopic assisted herniotomy is an effective, simple and feasible option for
      inguinal hernia in chidren without a high rate of complications.

PMID- 23113405
TI  - [Urethroplasty with lateral pedunculated flap for complicated hypospadias].
AB  - With the modern techniques, we can resolve almost the totallity of hypospadias.
      But there are patients with recurrent fistulas associated to uretral stenosis
      that can finish all the surgical possibilities. MATERIAL AND METHODS:
      Retrospective review. Lateral based flap uretroplasty consists in the exposition
      of the uretra, to reconstruct in one-stage the original neourethra with the
      lateral skin of the penis. RESULTS: From 2008, we have correct 5 patients with a
      mean age of 12,1 years (9-15) and a weight of 55,34 kg (22-98 kg). All of them
      were previously corrected 3 to 7 times, with recurrent fistulas. At the office,
      stenosis urethral was verified. Surgical correction was made in 90-110 minutes
      and results were positive in all patients, correcting the stenosis after a follow
      up of more than a year. Only the oldest two patients had present minimally glans
      fistula. CONCLUSIONS: Lateral based flap urethroplasty is a useful technique for
      the correction of the complicated fistulas, allowing the correction of the
      fistulas and the stenosis of the urethra.

PMID- 23113406
TI  - [Gastroschisis. Preterm elective cesarean and immediate primary closure: our
      experience].
AB  - PURPOSE: Our experience en treatment of gastroschisis using a protocol with
      elective preterm delivery by caesarean section at 34-35 weeks and immediate
      primary abdominal wall closure. METHODS: During a period of 18 month we treated 5
      patients with gastroschisis using the following management pathway: Starting at
      30th week of gestation, weekly ultrasound evaluation of fetal gut and pulmonary
      maturation with corticosteroids. Delivery by elective caesarean section between
      34-35 weeks or earlier if evidence of bowel compromise was reported en ultrasound
      study. Immediate surgical correction after birth with primary closure was
      preformed under control of abdominal pressure. RESULTS: Mean gestational age of
      our patient was 33,94 weeks, and mean birth weight was 2154 gr. None of the cases
      present inflammatory peel and we found no difficulties for reduction of the gut
      at time of surgery. Two patients presented an intestinal malrotation. Extubation
      was preformed 36-48 hours after surgery. We started a trofic diet at 3,6 days and
      parental nutrition was retired after a mean period of 15,8 days. The mean time of
      hospital stay was 33,4 days. One patient with intestinal obstruction had a
      consideriously increased length of hospital stay of 74 days. CONCLUSIONS: A
      management pathway for gastroschisis with selective preterm delivery by caesarean
      section and immediate surgical treatment probably reduces the experience of
      inflammatory peel. This pathway permits a early initiation of oral feeding,
      reduces times of parenteral nutrition and need of central catheters, and shortens
      length of hospital stay.

PMID- 23113407
TI  - [Laparoscopic pyeloplasty in pediatric patients: our experience].
AB  - The aim of this essay is to present our initial experience with laparoscopic
      pyeloplasty and highlight how some specific technical changes allowed us to
      improve our results. We performed a chart review of the patients that underwent
      laparoscopic pyeloplasty in our institution. We included patients older than 6
      months old with proved stenosis of the ureteropelvic junction. We compared our
      first patients with the last ones in which we performed laterocolic approach in
      all left pyeloplasties and included a modification of the technique to place an
      external ureteric stent. We performed 13 laparoscopic pyeloplasties, 8 male
      patients and 5 female. There were 3 right pyeloplasties (23%) and 10 left ones
      (77%). We performed transmesocolic approach in 2 cases (left) and laterocolic
      approach in 11. Mean surgical time was 184 minutes in the first 8 cases and 142
      in the 5 last ones. We had three cases of complications in the first group, two
      stents migrated to ureter and one postsurgical infection. In the last cases we
      had a postoperative bleeding. Laparoscopic approach is an effective option for
      pyeloplasty with similar results to those of the open approach in spite of a
      longer surgical time. Experience and specific surgical details allow us to reduce
      complication rate and surgical time.

PMID- 23113408
TI  - [Study of satisfaction of testicular prosthesis implantation in children].
AB  - Testicular absence may cause psychological trauma in children. It can be avoided
      by placing testicular prosthesis (TP). However there is no consensus on the
      optimal age of implantation. We evaluate the results of TP implantation and their
      complications, as well as patient and family satisfaction. MATERIAL AND METHODS:
      This is a retrospective study of TP implanted between 2004-2010 in our center.
      Variables analyzed are: age, size and side, indication, surgical technique,
      complications and comorbidity. Telephone survey was done by a single interviewer
      to 50 families. DATA COLLECTED: general family satisfaction, characteristics of
      the prosthesis (size, shape, location and consistency), body image and
      psychological situation of the child, duration of analgesia after surgery,
      reoperation rate, and family advice to other parents. Statistical analysis with
      SPSS-18.0. RESULTS: 107 prostheses were placed (4 bilateral, 64 left and 35
      rights) at a mean age of 70,10 +/- 58,6 months. The most common indication was
      cryptorchidism (48.2%). Initial inguinal approach in 69%, and simultaneous
      contralateral orchidopexy in 29.9%. Only one patient refused the prostheses. In
      71% the mother was interviewed. Parents consider size, shape and position
      appropriate in 55.6%, 66.7% and 82.22% respectively. Hard consistency of TP was
      considered in 82.3% of the patients. Psychological problems were absent in 86.7%.
      Nighty five percent would be willing to replace when it was necessary. Parents
      would recommend the intervention to parents in the same situation in 86.7%.
      CONCLUSION: Testicular prosthesis avoids psychological trauma. The lack of
      satisfaction regarding to the small size and hardness makes necessary to replace
      the TP in adulthood. An open question remains whether we should consider the
      placement of TP in early ages, or if we should establish some indications based
      on a more rational communication with the family.

PMID- 23113409
TI  - [Anderson-Hynes pyeloplasty in children under 2 years. Is the laparoscopy the
      technique of choice?].
AB  - OBJECTIVE: To analyze if the laparoscopic pyeloplasty is as effective as the open
      procedure in the ureteropelvic junction obstruction in patients under 2 years of
      age. PATIENTS AND METHODS: Pyeloplasties performed in children under 2 years of
      age between 2007 and 2010. Weight, pre and postoperative renal pelvis and calices
      diameter, operating time, hospital stay and complications were analyzed. RESULTS:
      We found no statistic differences in weight, complications, or pre and
      postoperative renal pelvis and calices diameter. However, we found differences in
      hospital stay and operating time (p<0.05). CONCLUSIONS: Laparoscopic pyeloplasty
      in children under 2 years of age is a good alternative technique for
      ureteropelvic junction obstruction, although operating time are still long.

PMID- 23113410
TI  - [High resolution surgery: one more step in out-patient surgery].
AB  - OBJECTIVES: One stop surgery (CAR: Cirugia Alta Resolucion) is a step forward in
      outpatient surgery. The new scheme simplifies ambulatory conventional surgery,
      achieves more satisfaction between patients and optimizes health resources.
      METHODS: By One stop surgery we mean the performance in the same day of both pre
      surgery assessment and surgical procedure. This new working way allows performing
      a surgical procedure in only one visit to the hospital, instead of the average
      four visits used before for surgical outpatients. Diagnosis, presurgery
      assessment and post surgery progress are made by the primary care paediatricians
      at theirs NHS offices. It is essential to maintain a close relationship between
      the Paediatric surgeons, the primary care paediatricians as well as with
      paediatric anaesthesiologists and nurses. An autoevaluation is made once a year
      in which quality survey results are made public and possible areas for
      improvement are identified, following the model proposed by the European
      Foundation for Quality Management (EFQM). RESULTS: We present 416 children
      treated following this scheme since 2008. Surgery is performed on the abdominal
      wall, genitals, skin and soft tissues. Families are satisfied with the quality of
      the whole medical and nursery received care as they qualified it with a 99%
      satisfaction index. Complications developed in less than 3%. CONCLUSIONS: One
      stop surgery is a progress in the outpatient surgery and, for us, it is a
      consolidated, continuously growing and constantly improving scheme of providing
      medical care.

PMID- 23113411
TI  - [Myofibroblastic tumor of the lung: clinical features and results in 9 children].
AB  - INTRODUCTION: Primary lung tumors in children are rare, being the myofibroblastic
      lung tumor (MLT) reported as the most common. Nevertheless the literature about
      it is scarce, and mostly consistent of case reports. The aim of this article is
      to describe the results obtained in a group of patients with this tumor treated
      in a tertiary pediatric hospital. METHODS: A single institution retrospective
      chart review was performed with institutional review board approval. All patients
      treated between 1990 and 2010 with diagnosis of MLT were included. Age, symptoms
      at presentation, surgical procedures, complications, histopathology and follow-up
      were reviewed. RESULTS: 9 patients were identified. The commonest symptoms at
      presentation were fever and cough (n=6), and seizures (n=2). Surgical treatment
      consisted in complete resection in 8 patients and partial resection in 1. To
      achieve this 3 patients underwent pneumonectomy and 6 lobectomy. Two of the
      patients with pneumonectomy required also a partial resection of the right atrium
      and both had cerebral lesions. The mean follow-up was 2.8 years (r:0.16-12) and
      all the patients that remained in follow-up (66%) are alive at the moment.
      DISCUSSION: Complete surgical resection in MLT is possible, however, to achieve
      this complex procedures and a multidisciplinary approach might be needed.
      Although the potential of distant metastasis is not clearly reported, we think
      that it is a topic that must be carefully revised.

PMID- 23113412
TI  - [Analysis of the medical decision in abdominal pain suggestive of acute
      appendicitis].
AB  - OBJECTIVES: Application of the theorem of Bayes for the study of the usefulness
      of complementary quantitative and qualitative assessment of the effectiveness of
      ultrasound diagnosis in order to provide the clinician with a tool to accurately
      assess the effectiveness of these tests in diagnosing abdominal pain appendix
      subject box. METHODS: Retrospective cohort of 184 patients treated from January
      2009 to June 2010 for abdominal pain suggestive of acute abdomen, of which 145
      were operated. Were established as predictors of appendiceal disease abdominal
      exploration, ultrasonography and plasma levels of CRP and leukocytes. The
      statistical methodology developed by the systematic Bayesian prior determination
      of ROC curve and calculation of odds and post-test probability as pretest
      probability based on physical examination. RESULTS: The ROC analysis cut-points
      set of quantitative tests on the values of WBC >12,800 and CRP >1.8 mg/dl.
      Applying the model to the white cell count increased clinical certainty of this
      test in 11.3 points and 13.9 PCR. The combined use of both the index rose 32
      points. The effectiveness of ultrasound method showed a statistically significant
      94% and an increase in diagnostic certainty of 48 points. DISCUSSION: It is
      recommended to base the development of protocols and clinical guidelines in
      practice of test ultrasound as first, and joint determination of inflammatory
      markers, when that was questionable or negative. Further studies are proposed to
      increase the clinical certainty to reduce laparotomy white and diagnostic delays
      in this condition.

PMID- 23113413
TI  - [Utility of urine levels of interleukins in the diagnosis of vesicoureteral
      reflux: a case-control study in children].
AB  - Invasive imaging methods that require catheterization are used for the diagnosis
      of vesicoureteral reflux. Our aim is to assess the usefulness of interleukin
      urinary levels for the diagnosis of reflux in children without urinary tract
      infection. METHODS: Case-control study in children who underwent a voiding
      cystourethrogram: forty cases diagnosed of reflux and 80 controls. Concentrations
      of IL-1beta, IL-6 and IL-8 related to creatinine levels (pg/micromol) were
      determined in urine samples in all. RESULTS: Sixty-two patients were males and
      fifty-eight females, with a mean age of 2.4 years. Indications for cystography
      were previous urinary tract infection in 78 cases (65%), prenatal diagnosis in 24
      cases (20%) and postnatal diagnosis of uropathy or family history in 18 cases
      (15.1%). No significant differences were observed between cases and controls in
      IL-1beta/creatinine and IL-6/creatinine levels. However, IL-8/creatinine levels
      were almost significant higher in case group (median 3.5 pg/micromol; SD 9.2)
      than in control group (median 1.54 pg/micromol; SD 3) (P=0.001). The odds ratio
      was 5.57 (CI95%: 1.51 a 20.60) (X(MH)=2.80; p=0.005). CONCLUSIONS: Urinary levels
      of IL-8/creatinine are elevated in children with vesicoureteral reflux, even in
      absence of urinary tract infection. It could be used as a non-invasive marker for
      detection of subclinical cases of disease.

PMID- 23113414
TI  - [Bronchoplastic surgery: tumorectomy in principal left bronchial tube in a 5
      month old child].
AB  - INTRODUCTION: Resection of bronchial tumors usually needs resection of the lung
      parenchyma ventilated by the ill bronchus. Surgery over a developing child must
      preserve the biggest amount of lung parenchyma as possible. We show a complete
      resection of a benign tumor from the left main-stem bronchus, without
      pneumonectomy. MATERIALS AND METHODS: Case report RESULTS: A 5 month girl
      presented with left hypoventilation. No significant previous dates. After
      bronchoscopy (with negative biopsy), chest radiograph and CT, she was diagnosed
      of a tumor in the mainstem left bronchus (20 x 15 mm) without metastatic
      extension. A sleeve resection of the tumor, with carinal reconstruction was
      performed. It was done under unipulmonary ventilation, with selective bronchial
      intubation. The patient was extubated in the operating room and the hospital stay
      was of 5 days. Follow up bronchoscopies shows no anastomotic stricture neither
      leakage. The patient is doing well 2 years after surgery. CONCLUSIONS: With this
      report and others in literature we can say that is possible to resect bronchial
      tumors in infancy without parenchymal resections.

PMID- 23113415
TI  - [Cherubism: diagnosis and treatment in the pediatric age].
AB  - Cherubism is a benign bone dysplasia of childhood, exclusively involving
      maxillary bones and spontaneous resolving after puberty in different grades.
      Approximately, 280 cases have been reviewed in the literature. It is an autosomal
      dominant disorder in which the normal bone is replaced by cellular fibrous and
      immature bone, resulting in painless symmetrical enlargement of the jaws.
      Diagnosis is based in clinical and radiological findings, confirmed by histology.
      Treatment is a controversial issue, and it is recommended surgical management as
      conservative as possible during the rapid growth phases. An aggressive case of
      cherubism is reported, diagnosed and followed since early childhood until
      puberty, with progressive involvement of facial bones developing in a disruption
      of facial contours and occlusion. The patient is treated by several surgical
      interventions oriented to minimize the aesthetic impact of the disease being as
      conservative as possible. The highlights of this case are the great proportion of
      the lesions, the functional and emotional disturbances brought out by these
      lesions and the difficulty to choose the most appropriate age and form of
      treatment.

PMID- 23113416
TI  - Experience and education of home health administrators and nursing home
      administrators and the relationship to establishment ownership.
AB  - Administrators in long-term care may have an important influence on quality of
      care. Limited prior research has described the characteristics of nursing home
      administrators. Despite growing emphasis on home health care as an alternative to
      nursing homes, almost no research has described the characteristics of
      administrators of home health agencies. Using the 2004 National Nursing Home
      Survey and the 2007 National Home and Hospice Care Survey, we describe the career
      experience of administrators, and examine the relationship between experience and
      education of administrators both within and across the nursing home and home
      health sectors. We also explore the characteristics of nursing homes and home
      health agencies, including establishment ownership (e.g., nonchain not-for
      profit), that are associated with being able to attract administrators with the
      most experience. We find that home health administrators have, on average, less
      experience than nursing home administrators. Among home health agencies,
      administrators with the least experience also tend to have less education. In
      nursing homes, administrators with less experience tend to have more education.
      Results from multivariate analysis suggest that chain for-profits may be the
      least able to attract experienced administrators. More research on the effects of
      different levels of experience and education among administrators is needed.

PMID- 23113417
TI  - Antenarratives to inform health care research: exploring workplace illness
      disclosure for people with multiple sclerosis (MS).
AB  - I share Boje's (2001) concept of antenarratives as a useful means of presenting
      qualitative health care research, especially their capacity to share illness
      related stories which may be fragmented, non-linear, sometimes incoherent, and
      often speculative. I do this to offer insights to health care professionals that
      might maximize the health care outcomes for those they serve. An Australian based
      qualitative research project explored the lived experience of what life is really
      like for a person with Multiple Sclerosis (MS). Rather than presenting a
      traditional, narrative based, coherent and saturated theme, I present
      antenarratives that vivify the lived experience of illness disclosure.
      Antenarratives have the capacity to share key elements of experience in ways that
      can edify health care practitioners concerned with offering support that consists
      of more than prescriptive solutions and certain advice.

PMID- 23113418
TI  - Management challenges at the intersection of public policy environments and
      strategic decision making in public hospitals.
AB  - Hospitals in the United States are heavily impacted by public policies that
      affect them. For example, Medicare and Medicaid programs account for more than
      half the revenue in most of the nation's almost 5,000 community hospitals,
      including the almost 1,100 public hospitals controlled by state and local
      governments (American Hospital Association, 2012). The public hospitals are
      especially closely aligned with and controlled by governmental entities compared
      with hospitals with other kinds of sponsorship. This article addresses the
      management challenges at the intersection of the strategic management of public
      hospitals and their public policy environments. Public hospitals are complicated
      entities designed not only to provide health services but also in many cases to
      play key roles in health-related research and education and to play important
      general economic development roles in their communities. The multi-faceted
      strategic decision making in these organizations is as heavily affected by their
      public policy environments as by their business, demographic, technological or
      other external environments. Effectively managing the intersection of their
      public policy environments and their strategic management is indeed vital for
      contemporary public hospitals. This article is intended to clarify certain
      aspects of this intersection through a description and model of the strategic
      activity in public hospitals and the connection between this activity and their
      external environments. Specific attention is focused on the concept of public
      policy environments and their features. Attention is also given to how managers
      can assess public policy environments and incorporate the results into strategic
      activities.

PMID- 23113419
TI  - Risk of exposure to second hand smoke for adolescents in Las Vegas casinos: an
      evaluation of the Nevada Clean Indoor Air Act.
AB  - Since the Surgeon General's groundbreaking report of 1964, "Smoking and Health,"
      the medical and scientific communities have uncovered the devastating effects of
      tobacco smoke on health. In reaction to these findings, local and state
      governments have enacted a variety of clean air acts to prevent unnecessary
      exposure to this known carcinogen. The Nevada Clean Indoor Air Act (NCIAA), a non
      comprehensive smoke-free law, permits smoking in designated areas of casinos,
      bars, and taverns. With many Las Vegas casinos catering to all ages, this study
      was designed to evaluate the efficacy of NCIAA in protecting children from second
      hand smoke exposure. Using a device that measures ambient air particle matter
      concentrations, this study sampled the air quality in 15 casino gaming areas and
      corresponding non-smoking, children-friendly areas. The results indicate that
      current policy fails to preserve indoor air quality in these children-friendly
      areas. Furthermore, this research suggests the adoption of a more comprehensive,
      100% smoke-free policy as the only effective remedy.

PMID- 23113420
TI  - [The 5th Ukrainian Conference "Surgical Treatment of Obesity and Related
      Metabolic Disorders". Abstracts].

PMID- 23113421
TI  - [Mobilization of the stomach and colon using high-frequency electric welding of
      tissues apparatus].
AB  - The experience of the native high-frequency electrical generator 300M EC-1
      "Patonmed" for mobilization of advanced vascular network, particularly stomach
      and colon are presented. The variants of modes depending on the diameter of blood
      vessels and accompanied diseases are suggested.

PMID- 23113422
TI  - [Surgical treatment of patients with necrotizing pancreatitis in the phase of
      septic complications].
AB  - The results of staging surgical treatment of necrotizing pancreatitis in the
      phase of septic complications were presented. Using of staging minimally invasive
      techniques in the treatment permit to reduce of postoperative complications rate
      up to 42%, mortality--up to 22%.

PMID- 23113423
TI  - [Experience with Y-shaped anastomosis in surgical treatment of acute colonic
      occlusion ileus of tumor genesis].
AB  - The results of the Y-shaped anastomosis during resection of the colon left half
      with a resectable tumor on a background of acute colonic occlusion ileus in 35
      patients were analyzed. Postoperative complications occurred in 16 patients. The
      Y-shaped anastomosis formation is an operation of choice during the resection
      treatment of colon cancer complicated by occlusion ileus. Carrying out such
      interventions poses a number of benefits when the second (recovery) stage of
      colon cancer surgical treatment.

PMID- 23113424
TI  - [Multiple endocrine neoplasia syndrome type 2].
AB  - Multiple endocrine neoplasia (MEN) syndrome--is a hereditary disease which is
      characterized by synchronous or metachronous development of benign (adenoma,
      hyperplasia) or malignant tumors in the endocrine organs. The presence of
      medullary thyroid carcinoma and pheochromocytoma are mandatory requirements of
      MEN 2 syndrome. The purpose of our study was to perform timely diagnosis and
      optimal surgical treatment of patients with MEN 2 syndrome. Over the 1999-2009
      years in the clinic we have diagnosed the MEN 2 syndrome in 5 patients, of whom
      two women were sisters. In all patients we observed medullary thyroid carcinoma
      and pheochromocytoma. Two patients had bilateral pheochromocytoma, and the
      clinical course was characterized with mild arterial hypertension. Primary
      hyperparathyroidism was observed in 2 patients. In the near relatives of patients
      with MEN 2 syndrome it must measure calcitonin, catecholamines, calcium rate,
      conduct ultrasound examination of the neck and retroperitoneal space.

PMID- 23113425
TI  - [Ansell: optimal defense of the surgeons hands].

PMID- 23113426
TI  - Workplace injuries and the take-up of Social Security disability benefits.
AB  - Workplace injuries and illnesses are an important cause of disability. State
      workers' compensation programs provide almost $60 billion per year in cash and
      medical-care benefits for those injuries and illnesses. Social Security
      Disability Insurance (DI) is the largest disability insurance program in the
      United States, with annual cash payments to disabled workers of $95 billion in
      2008. Because injured workers may also receive DI benefits, it is important to
      understand how those two systems interact to provide benefits. This article uses
      matched state workers' compensation and Social Security data to study the
      relationship between workplace injuries and illnesses and DI benefit receipt. We
      find that having a lost-time injury substantially increases the probability of DI
      receipt, and, for people who become DI beneficiaries, those with injuries receive
      DI benefits at younger ages. This relationship remains robust even after we
      account for important personal and work characteristics.

PMID- 23113427
TI  - Longitudinal patterns of Medicaid and Medicare coverage among disability cash
      benefit awardees.
AB  - This article explores the role of the Social Security Disability Insurance (DI)
      and Supplemental Security Income (SSI) cash benefit programs in providing access
      to public health insurance coverage among working-aged people with disabilities,
      using a sample of administrative records spanning 84 months. We find that complex
      longitudinal interactions between DI and SSI eligibility determine access to and
      timing of Medicare and Medicaid coverage. SSI plays an important role in
      providing a pathway to Medicaid coverage for many low-income individuals during
      the 29-month combined DI and Medicare waiting periods, when Medicare coverage is
      not available. After Medicare eligibility kicks in, public health insurance
      coverage is virtually complete among awardees with some DI involvement. Medicaid
      coverage continues at or above 90 percent after 2 years for SSI-only awardees.
      Many people who exit SSI retain their Medicaid coverage, but the gap in coverage
      between stayers and those who leave SSI increases over time.

PMID- 23113428
TI  - Income replacement ratios in the Health and Retirement Study.
AB  - This article describes the income replacement ratio as a measure of retirement
      income adequacy and identifies several issues analysts must consider when
      calculating a replacement ratio. The article presents the income replacement
      ratios experienced by participants in the original sample cohort of the Health
      and Retirement Study (HRS), who were born between 1931 and 1941. Replacement
      ratios are shown by the respondent's birth cohort, age when first classified as
      retired in the HRS, and preretirement income quartile. Median replacement ratios
      fall as the retirement period grows longer.

PMID- 23113429
TI  - Shifting income sources of the aged.
AB  - Traditional defined benefit pensions, once a major source of retirement income,
      are increasingly giving way to tax-qualified defined contribution (DC) plans and
      individual retirement accounts (IRAs). This trend is likely to continue among
      future retirees who have worked in the private sector. This article discusses the
      implications of those trends for the measurement of retirement income. We
      conclude that Census Bureau's Current Population Survey (CPS), one of the primary
      sources of income data, greatly underreports distributions from DC plans and
      IRAs, posing an increasing problem for measuring retirement income in the future.
      The CPS and other data sources need to revise their measures of retirement income
      to account for periodic (irregular) distributions from DC plans and IRAs.

PMID- 23113430
TI  - The growth in applications for Social Security Disability Insurance: a spillover
      effect from workers' compensation.
AB  - We investigate the determinants of application for Social Security Disability
      Insurance (DI) benefits in approximately 45 jurisdictions between 1981 and 1999.
      We reproduce findings of previous studies of the determinants of DI application
      then test the additional influence of changes to workers' compensation program
      benefits and rules on DI application rates. Our findings indicate that the
      programs are interrelated: When workers' compensation benefits declined and
      eligibility rules tightened in the 1990s, the DI application rate increased.

PMID- 23113431
TI  - A paradox: military graduate medical education, an open letter to GME.

PMID- 23113432
TI  - Re: Veterans with PTSD require VA services for medical illness as well as
      psychological support.

PMID- 23113433
TI  - RE: histopathological documented cryptococcal lung lesion associated with
      diabetes mellitus and dental abscess.

PMID- 23113434
TI  - RE: Cason EM. Air Force Hearing Conservation Program data 1998-2008: a cross
      sectional analysis of positive threshold shifts. mil med 2012; 177(5): 589-93.

PMID- 23113435
TI  - Medical stability operations--one approach to transforming the Department of
      Defense Military Health System.
AB  - The Department of Defense Instruction (DoDI) 6000.16 entitled Military Health
      Support for Stability Operations was published in 2010 and established policy
      that Medical Stability Operations (MSOs) would be a core military mission. The
      instruction set out to institutionalize how the Military Health Support (MHS)
      would effectively support MSOs and assist in bridging the gap with other actors
      operating in the same space. What is less clear is the current status of the MHS
      in accomplishing the responsibilities outlined in the DoDI. Even more concerning
      is how these efforts will support the "new" strategic guidance for the DoD
      published in January 2012 that states U.S. forces will no longer be sized to
      conduct large-scale, prolonged stability operations. In the absence of a publicly
      available DoDI 6000.16 implementation strategy, this article proposes the use of
      an organizational transformation process developed by internationally acclaimed
      leadership and organizational change expert Dr. John Kotter. The eight-step
      process is used as a framework to explore ways to effectively transform the DoD
      in meeting the intent of the MSOs DoDI. The past decade has transformed how
      service members think about MSOs. Now is the time to transform the MHS with
      urgency to institutionalize these thoughts.

PMID- 23113436
TI  - Mission essential fitness: comparison of functional circuit training to
      traditional Army physical training for active duty military.
AB  - Appropriate and effective physical fitness training is imperative for soldier
      survival and mission success. The purpose of this study was to determine the
      effects of Mission Essential Fitness (MEF) circuit-style training program
      compared to standard Army Physical Readiness Training (APRT) on fitness,
      physiological, and body composition changes. Active duty Army personnel were
      randomly assigned to two groups (MEF = 34 or APRT = 33) for 8 weeks of training
      (15 sessions each). The MEF program included functional movements focused on
      strength, power, speed, and agility. Fifteen exercises were performed
      continuously for 60 to 90 seconds for 45 minutes. Baseline and post-test measures
      included the Army physical fitness test, physiological indicators, body
      composition, and additional fitness indicators. One-way analysis of covariance
      models indicated that MEF participants significantly increased their push-ups (p
      = 0.033), bench press (p = 0.001), and flexibility (p = 0.003) and significantly
      decreased their 2-mile run (p = 0.003) and step test heart rate (p = 0.004)
      compared to participants doing APRT. Both groups maintained body composition (p >
      0.05) and reported no injuries. The MEF training program safely improved muscular
      strength and endurance, cardiovascular endurance, and flexibility, supporting
      functional fitness circuit-style exercise training for military personnel.

PMID- 23113437
TI  - The effects of a human patient simulator vs. a CD-ROM on performance.
AB  - OBJECTIVES: Military health care personnel need to have skills relative to caring
      for patients on the battlefield. No studies have compared the two teaching
      strategies of using the human patient simulator (HPS) and a CD-ROM in caring for
      combat injuries. The objective of this study was to determine if there were
      statistically significant differences in HPS and CD-ROM educational strategies
      relative to caring for patients who have trauma. METHODS: A pretest/post-test
      prospective experimental design was used. Anesthesia students were randomly
      assigned to one of three groups: HPS, CD-ROM, or a control group. A valid and
      reliable instrument, Combat Performance, was used to evaluate the participant's
      ability to give care to trauma patients. RESULTS: A repeated analysis of variance
      and a least significant difference post hoc test were used to analyze the data.
      The HPS group performed better than the CD-ROM and control groups relative to
      performance (p = 0.001). There was no difference between the CD-ROM and control
      group (p = 0.171). DISCUSSION: We speculate that the HPS group performed better
      than the CD-ROM group because of the realism. CONCLUSION: In this study, the HPS
      method of instruction was a more effective method of teaching than the CD-ROM
      approach.

PMID- 23113438
TI  - Injuries, changes in fitness, and medical demands in deployed National Guard
      soldiers.
AB  - PURPOSE: To characterize noncombat injury/illness, determine changes in physical
      fitness, and evaluate the influence of these changes on medical resource
      utilization by National Guard (NG) Soldiers. METHODS: Fifty-four Soldiers from
      the Arizona NG completed pre- and postdeployment fitness testing. Additionally,
      individual deployment medical records were inventoried. RESULTS: The majority of
      noncombat-related medical visits (41%) were musculoskeletal in nature, followed
      by miscellaneous (33%) and respiratory (13%). Soldiers experienced significant
      decreases in percent fat mass (-11.1%, p < 0.001) and VO2 peak (-10.8%, p <
      0.001). There were significant increases in push-ups (16.4%, p < 0.001), sit-ups
      (11.0%, p = 0.001), bench-press (10.2%, p < 0.001), and back squat (14.2%, p <
      0.001) measures. VO2 peak was inversely correlated to medical resource
      utilization (r = -0.45 to -0.28, p < or = 0.05). The tertile of Soldiers
      experiencing the sharpest declines in VO2 peak had significantly more medical
      visits over the course of the deployment than the other two tertiles (8.0 vs. 2.6
      vs. 3.1 medical visits/Soldier, p < or = 0.05). CONCLUSION: The predominate
      noncombat medical issue was musculoskeletal injury. NG Soldiers improved their
      body composition, strength, and endurance but experienced significant declines in
      aerobic fitness while deployed. These data document the association between
      declining aerobic fitness and increased utilization of medical resources.

PMID- 23113439
TI  - Perceived stigma and barriers to mental health care in Marines attending the
      Combat Operational Stress Control program.
AB  - The Department of Defense is aggressively addressing combat stress reactions
      (CSRs) through comprehensive Combat/Operational Stress Control (COSC)
      briefings/programs and referral resources for the prevention, identification, and
      treatment of stress reactions. The purpose of this study was to develop and
      administer a survey to assess perceptions of CSRs and barriers to care which
      affect help-seeking behavior in Marines attending the COSC program. A sample of
      553 U.S. Marine Corps Officers and Enlisted personnel from Air (44%), Logistics
      (38%), and Infantry (18%) communities were recruited for the survey. The results
      suggested that misconceptions and stigma about CSRs still persist in Marines. The
      findings reinforced the need to facilitate treatment utilization by focusing on
      mental health-related stigma as well as organizational barriers.

PMID- 23113440
TI  - Association between mental health conditions diagnosed during initial eligibility
      for military health care benefits and subsequent deployment, attrition, and death
      by suicide among active duty service members.
AB  - OBJECTIVE: To examine incidence of mental health diagnoses during initial service
      of U.S. active duty military members and identify associations with deployment,
      attrition, and suicide. METHODS: A retrospective cohort of 576,502 service
      members (SMs) newly enlisted between 2003 and 2006 was identified. Data included
      medical encounter, deployment and attrition, and suicide. Multivariable logistic
      regression models examine the association between mental health diagnoses coded
      within the SMs' first 6 months of eligibility for health care benefits and
      deployment. Multivariable Cox proportional hazards models quantify the
      association between mental health diagnoses and attrition and suicide. RESULTS:
      The cumulative incidence of mental health diagnoses was approximately 9% at 6
      months of service. Adjustment, depressive, and anxiety disorders were most
      common. Those with any mental health diagnosis during initial eligibility had
      increased risk of early attrition and were 77% less likely to deploy. Early
      mental health diagnoses were not statistically significantly associated with
      death by suicide. CONCLUSION: Mental health diagnoses during initial eligibility
      are common and associated with reduced odds of deployment and increased risk of
      early attrition. Policies designed to either retain or discharge SMs with a
      mental health diagnosis identified during initial training merit close
      examination in light of these findings.

PMID- 23113441
TI  - Relationship between mechanism of injury and neurocognitive functioning in
      OEF/OIF service members with mild traumatic brain injuries.
AB  - Military personnel deployed to combat theaters in Iraq and Afghanistan are at
      risk of sustaining mild traumatic brain injuries (mTBI) from causes such as
      improvised explosive devices, motor vehicle accidents, and falls. Despite the
      high incidence of mTBI in deployed personnel, questions remain about the effects
      of blast-related vs. non-blast-related mTBI on acute and long-term sequelae. This
      investigation is a retrospective review of service members who presented for
      evaluation of suspected mTBI and underwent neurocognitive screening evaluation,
      mTBI diagnosis was made by semistructured clinical interview. Only individuals in
      whom mechanism of injury could be determined (blast vs. non-blast) were included.
      Sixty individuals were included in the final sample: 32 with blast mTBI and 28
      with non-blast mTBI. There were no differences between the blast-related and non
      blast-related mTBI groups on age, time since injury, combat stress symptoms, or
      headache. Analysis of variance showed no significant between-group differences on
      any of the neurocognitive performance domains. Although speculation remains that
      the effects of primary blast exposure are unique, the results of this study are
      consistent with prior research suggesting that blast-related mTBI does not differ
      from other mechanisms of injury with respect to cognitive sequelae in the
      postacute phase.

PMID- 23113442
TI  - Eating disorders, post-traumatic stress, and sexual trauma in women veterans.
AB  - We examine lifetime eating disorders (EDOs) and associations with post-traumatic
      stress disorder (PTSD) and sexual trauma during various stages of the life course
      (childhood, during military service, and lifetime) among women veterans. The
      sample included 1,004 women aged 20 to 52 years who had enrolled at 2 Midwestern
      Veterans Affairs Medical Centers or outlying clinics completed a retrospective
      telephone interview. Over 16% reported a lifetime EDO (4.7% had received a
      diagnosis, and an additional 11.5% self-reported suffering from an EDO).
      Associations were found between lifetime EDO, PTSD, and sexual trauma.
      Relationships maintained significance for both diagnosed and self-reported EDOs
      as well as lifetime completed rape and attempted sexual assaults. Sexual trauma
      during military service was more strongly associated with lifetime EDOs than
      childhood sexual trauma. The significant associations found between EDOs, PTSD,
      and sexual trauma indicate that EDO screening among women veterans with PTSD or
      histories of sexual trauma may be warranted.

PMID- 23113443
TI  - 2003-2009 marital functioning trends among U.S. enlisted soldiers following
      combat deployments.
AB  - OBJECTIVE: This study examined 2003-2009 trends in three marital functioning
      indicators: marital quality, infidelity, and separation/divorce intent, and in
      marital dissolution rates among U.S. soldiers. METHODS: Marital functioning
      trends were examined with cross-sectional postdeployment sample data collected
      under the Land Combat Study from married, male, enlisted soldiers who had
      deployed to Iraq or Afghanistan (n = 5,928). Marital dissolution rates were
      examined with population data (n = 1,895,571). The relationships between time
      (measured by year) and all study variables were analyzed with chi2 tests of
      association, analysis of variance, and logistic regression analyses adjusting for
      combat exposure, mental and physical health, and demographic variables. RESULTS:
      Marital quality has declined, and reports of past-year infidelity and
      separation/divorce intent have increased between 2003 and 2009. However, no
      increases were observed in marital dissolution rates. CONCLUSIONS: The results
      indicate that more proximal indicators of marital functioning such as decreased
      marital quality, infidelity, and separation/divorce intent may better illustrate
      the strain that increased deployment tempo exerts on marital relationships. The
      findings provide a better understanding of how Army marriages have been affected
      by the wars, and suggest that further inquiry is needed on military marriages.

PMID- 23113444
TI  - Interpersonal conflict and referrals to counseling among married soldiers
      following return from deployment.
AB  - Deployment represents a significant potential strain on military families. The
      impact of postdeployment stresses may be increased if family coping resources are
      diminished by returning service members' physical injuries, mental health issues,
      or substance abuse. This article examines the health and mental health correlates
      of self-reported concerns regarding interpersonal conflict among married soldiers
      following return from deployment and the likelihood that soldiers acknowledging
      such concerns are referred to counseling services. Among 20,166 married Army
      soldiers completing Post-Deployment Health Reassessments, 18% reported having
      experienced serious interpersonal conflict with their spouse, family members,
      close friends, or coworkers. Results indicate that interpersonal conflict was
      more common among those who reported health problems, depression, post-traumatic
      stress disorder, and alcohol abuse. Among soldiers reporting interpersonal
      conflict and not already receiving services, 11% were referred to service.
      Findings support the need to communicate with soldiers and their spouses about
      the availability of services following return from deployment and to continue
      efforts to reduce stigma associated with seeking treatment.

PMID- 23113445
TI  - Postdeployment alcohol use, aggression, and post-traumatic stress disorder.
AB  - Current military personnel are at risk of developing serious mental health
      problems, including chronic stress disorders and substance use disorders, as a
      result of military deployment. The most frequently studied effect of combat
      exposure is post-traumatic stress disorder (PTSD). High-risk behaviors, including
      alcohol use and aggression, have been associated with PTSD, but the optimal
      cutoff score on the PTSD Checklist (PCL) for determining the risk for these
      behaviors has not been clearly delineated. Using postdeployment active duty (AD)
      and Reserve component military personnel, the relation between various cutoff
      scores on the PCL and engaging in high-risk behaviors was examined. AD personnel,
      for every outcome examined, showed significantly greater odds for each problem
      behavior when PCL scores were 30 or higher compared to those with PCL scores in
      the 17 to 29 range. A similar pattern was shown for Reserve component personnel
      with respect to several problem behaviors, although not for alcohol use
      behaviors. The differences in problem behaviors for these two populations may be
      an indication that deployment experiences and combat exposure affect them
      differently and suggest that despite lower critical PCL scores, AD personnel may
      be at higher risk for developing problems as a function of the deployment cycle.

PMID- 23113446
TI  - Alcohol abuse or dependence in the military aviator: guidance for the non-flight
      surgeon.
AB  - Alcohol is tightly interwoven with the image and culture of aviation. When
      alcohol is combined with aviation, the result can be fatal to aircrew,
      passengers, and bystanders. Alcohol has been implicated in 8 to 12% of fatal
      general aviation accidents. With approximately 10% of the general population
      estimated to have alcohol abuse or dependence, alcohol issues are similarly
      common among aviators. Clear and concise guidelines exist to address alcohol
      disorders in both civilian and military aviation. However, few health care
      providers outside the aviation community are aware of these guidelines. When an
      aviator presents with an alcohol disorder, the well-intentioned provider may be
      reluctant to address the issue because of poor understanding of the occupational
      implications or a misplaced effort to preserve the aviator's career. However,
      proper therapy often permits the aviator to continue flying duties without
      adverse career impact. This review will discuss the implications, guidelines, and
      prognosis for the alcohol-dependent aviator and provide resources to enable the
      responsible health care provider to return the pilot to flight status as soon as
      practicable. Knowledge of these civilian and military guidelines will help close
      the treatment and communication gaps between aeromedical specialists and other
      medical professionals.

PMID- 23113447
TI  - Use of portable sleep monitors to diagnose sleep apnea during predeployment
      assessment.
AB  - INTRODUCTION: Portable sleep monitors (PMs) may be more expeditious and
      convenient than in-laboratory sleep studies in diagnosing obstructive sleep apnea
      (OSA). We report for the first time the use of PMs in a military population to
      demonstrate feasibility in predeployment assessments. METHODS: A nested,
      descriptive study was undertaken at 7 military medical facilities as part of a
      larger clinical trial. Subjects answered two questionnaires to identify OSA
      symptoms and used an ApneaLink Plus portable monitor to test for OSA. Descriptive
      statistics were used to characterize the subjects and to report results of PM
      use. RESULTS: 101 subjects were enrolled, and 77 subjects completed the study.
      4.0% of subjects did not tolerate PM use. We found 15 subjects with OSA, with
      mean age of 31.4 +/- 12.8 years, mean body mass index of 33.0 +/- 7.4 kg/m2, and
      mean apnea-hypopnea index of 19.6 +/- 13.9 per hour. Subjects with OSA were more
      likely to have high pretest probability of disease than those without OSA.
      CONCLUSION: We demonstrate that PMs are well-tolerated and can successfully
      identify OSA in those with high pretest probability. We propose a method to
      implement PM use during predeployment assessments.

PMID- 23113448
TI  - Why strong tobacco control measures "can't" be implemented in the U.S. Military:
      a qualitative analysis.
AB  - The Institute of Medicine recently called for a tobacco-free military, citing
      evidence that high rates of tobacco use harm readiness and create enormous costs
      for the Department of Defense and the Veterans Administration. The pro-tobacco
      activities of the tobacco industry and others, sometimes supported by military
      authorities even when prohibited by policy, have created a culture highly
      hospitable to smoking. Through qualitative secondary analysis of data from
      interviews and focus groups, this article explores the reasons enlisted personnel
      and their supervisors, installation tobacco control managers, and service policy
      leaders give for why tobacco control policy change "cannot" effectively be
      achieved. Three primary reasons were given: policies would impinge on the "right
      to smoke," policies would be unenforceable and lead to disciplinary breakdown,
      and the rights of civilian workers on military installations precluded policy
      enforcement. Yet evidence suggests that these reasons are not only invalid, but
      inconsistent with military policies addressing other threats to the health of
      personnel. This pervasive tobacco "exceptionalism" is a significant barrier to
      achieving a tobacco-free military. The military, Congress, and the President
      should re-evaluate the "can'ts" that have prevented effective action, and act to
      regulate and eventually abolish tobacco use in the armed forces.

PMID- 23113449
TI  - Maternal depression screening during prenatal and postpartum care at a Navy and
      Marine Corps military treatment facility.
AB  - Maternal depression in the prenatal and postpartum periods is an important
      concern for women, infants, and families. Military family life may create some
      unique stressors, including operational deployment of an active duty husband,
      which increase perinatal depression challenges for women. This study examined
      depression screening scores, based on a modified Edinburgh Postpartum Depression
      Scale, among women receiving obstetric care at a military hospital serving a Navy
      and Marine Corps community. Among 3,882 surveys collected between 2007 and 2009
      from women at various points in their prenatal or postpartum care, the proportion
      with scores indicative of high risk for clinical depression was relatively low at
      4.6%. However, scores were significantly higher at the initial obstetric visit
      among women who reported their husband as currently deployed, and scores were
      significantly higher at the postpartum visit among women who reported their
      husband as currently deployed or planning to deploy. These results underscore the
      importance of evaluating all aspects of the military family life experience when
      providing perinatal care to women in military families.

PMID- 23113450
TI  - Incidence of anemia among obstetric patients in an Appalachian teaching clinic.
AB  - OBJECTIVE: The purpose of this study is to determine the incidence of iron
      deficiency anemia in an obstetrics clinic with a secondary objective to determine
      predictors of iron deficiency anemia. METHODS: This is a retrospective study of
      obstetric patients from the Charleston Area Medical Center Women's Medicine
      Center, a clinic at Women and Children's Hospital. Data were collected on Women's
      Medicine Center patients who delivered at Women and Children's Hospital during a
      1-year interval, through chart review linked with hospital database and birth
      certificate data for comorbidities. RESULTS: Inclusion criteria were met by 685
      patients. Anemia was present in 32/619 (5.2%) at intake and in 191/670 (28.5%) at
      delivery. The prevalence throughout pregnancy was 35.6%. Anemia was detected at
      first encounter or at 28 weeks in 123 (18.0 %) patients who were also tested at
      delivery. Of the 52 (42.3%) who received iron supplementation, 35(67.3 %)
      remained anemic at delivery. There were no statistically significant predictors.
      CONCLUSION: Anemia continues to plague obstetrical patients and its prevalence in
      our patient population was surprisingly high. Further investigation is warranted
      to better understand the apparent ineffectiveness of iron supplementation.

PMID- 23113451
TI  - Occupational effect on the occurrence of idiopathic venous thromboembolism.
AB  - Few studies have explored the effects of various occupations on venous
      thromboembolism occurrence. We examined idiopathic venous thromboembolism (IVTE)
      occurrence by occupation, body size, and age in the U.S. military. To capture
      idiopathic cases, exclusion criteria included recognized venous thromboembolism
      risk factors. Each case was matched to three controls on branch of service, sex,
      rank/grade, race, and education level. Body mass index, age, and occupation were
      analyzed with chi2 and logistic regression. Of 2,167 cases, most were male (87%),
      white (69%), enlisted (78%), averaging 36 years old. IVTE odds increased with age
      (p < 0.001). Every occupation showed greater odds than pilots/aircrew (p <
      0.001), especially infantry/artillery/combat arms, which showed twice the odds,
      followed by health care workers. Normal weight was protective, especially in
      pilots/aircrew (OR 0.52, p = 0.03) and repair/engineering (OR 0.72, p < 0.001).
      Our analysis found a lower risk of IVTE among pilots and aircrew compared to
      other military occupations. Body size had less impact than expected in aircraft
      and vehicle operators. Greater odds in health care workers and
      infantry/artillery/combat arms than in pilots/aircrew and armor/motor transport
      occupational groups may reflect prolonged standing. Limitations include potential
      miscoding of health records and potential misclassification. Future IVTE research
      should explore job functions and worker characteristics.

PMID- 23113452
TI  - Meningitis admitted to a military hospital: a retrospective case series.
AB  - Meningitis is a common admission diagnosis. No case series or descriptive studies
      on meningitis have recently been published. Additionally, no recent data exist on
      meningitis in the U.S. Military Health System. We reviewed charts of adult
      patients admitted to Naval Medical Center San Diego between January 2004 and
      December 2008 with an admission diagnosis of meningitis. Charts were excluded if
      they did not meet our case definition of meningitis, if missing data, or if
      meningitis was nosocomial or iatrogenic. We reviewed results of cerebrospinal
      fluid cultures during this period. We compared rates and characteristics, and
      outcomes of bacterial and aseptic meningitis. Two hundred twenty-one cases met
      our criteria. Of these, 208 were aseptic. Cerebrospinal fluid polymerase chain
      reaction testing was positive for enteroviruses and herpes simplex viruses in 42
      (20.2%) and 17 (8.2%) cases, respectively. Of culture/polymerase chain
      reaction/serologically positive cases, the pathogens were Neisseria meningitidis
      (3), Streptococcus pneumoniae (3), viridans streptococci (2), Cryptococcus
      neoformans (2), Coccidioides immitis (2), and Mycobacterium tuberculosis (1).
      Three patients had poor outcomes: one died from S. pneumoniae and two had long
      term neurologic deficits. Meningitis is a common admission diagnosis, but serious
      virulent pathogens are uncommon and adverse outcomes are rare.

PMID- 23113453
TI  - Spontaneous heterotopic pregnancy successfully treated via laproscopic surgery
      with subsequent viable intrauterine pregnancy: a case report.
AB  - BACKGROUND: Heterotopic pregnancy (HP) refers to the presence of simultaneous
      pregnancies at two different sites of implantation, one intrauterine and the
      other extrauterine. The incidence of HP has increased in recent years secondary
      to a rise in the use of assisted reproductive technologies (ART). CASE: A 34-year
      old woman, without risk factors for multiple pregnancies, presented with a
      spontaneous hypertopic pregnancy to a military facility. The ectopic pregnancy
      was successfully treated via laparoscopic surgery. She maintained a viable
      intrauterine pregnancy and was 32 weeks gestation with no complications at the
      time of submission. DISCUSSION: This case highlights the importance of
      maintaining a wide differential in a patient who presents with elevated Beta
      human Chorionic Gonadotropin Hormone (B-HCG) levels, which continue to rise, as
      well as signs and symptoms consistent with ectopic pregnancy. CONCLUSION:
      Currently the rate of ART is rising; therefore, the expected cases of HP will
      likely continue to rise. At this time, there are no standard protocols for
      treatment and diagnosis of HP; this is an area that should be further researched
      in order to provide the best medical care for these women, the intrauterine
      pregnancy and future fertility.

PMID- 23113454
TI  - Chinese scalp acupuncture relieves pain and restores function in complex regional
      pain syndrome.
AB  - Complex Regional Pain Syndrome (CRPS) can result from trauma or after surgery. It
      is often difficult to manage effectively. If not recognized early, it can result
      in significant debilitation. Symptoms attributed to CRPS include neuropathic
      pain, allodynia, sudomotor changes, and decreased range of motion. It can occur
      with (Type II) or without (Type I) nerve injury. A number of soldiers sustaining
      extremity injuries during combat have manifested these symptoms. Two subjects
      were diagnosed with CRPS after sustaining upper extremity injuries during
      military operations. After failing conservative treatment, Chinese Scalp
      Acupuncture (CSA) was used once to twice a week for 1 to 4 weeks. CSA resulted in
      improvement in the pain visual analog scale or numeric rating scale by over 80%
      in two soldiers with upper extremity CRPS. Additionally, decreased sensory
      changes and improved function were noted on exam and therapy assessments.
      Notably, the pain reduction, functional improvement, and normalization of
      sensation have been fully maintained between treatments. The treatment response
      had been sustained at 20-month follow-up with no recurrence. CSA provided lasting
      pain reduction, and improved function and sensation in this group of combatants
      with upper extremity CRPS.

PMID- 23113455
TI  - Does an isolated allergic reaction increase the risk of anaphylaxis?

PMID- 23113456
TI  - Case report: treatment of male subfertility with dietary supplements.

PMID- 23113459
TI  - Appropriate antibiotic use: family physicians have the power of the pen.

PMID- 23113460
TI  - Oral antihistamine/decongestant/analgesic combinations for the common cold.

PMID- 23113461
TI  - Antibiotic use in acute upper respiratory tract infections.
AB  - Upper respiratory tract infections account for millions of visits to family
      physicians each year in the United States. Although warranted in some cases,
      antibiotics are greatly overused. This article outlines the guidelines and
      indications for appropriate antibiotic use for common upper respiratory
      infections. Early antibiotic treatment may be indicated in patients with acute
      otitis media, group A beta-hemolytic streptococcal pharyngitis, epiglottitis, or
      bronchitis caused by pertussis. Persistent cases of rhinosinusitis may
      necessitate the use of antibiotics if symptoms persist beyond a period of
      observation. Antibiotics should not be considered in patients with the common
      cold or laryngitis. Judicious, evidence-based use of antibiotics will help
      contain costs and prevent adverse effects and drug resistance.

PMID- 23113462
TI  - When to suspect a genetic syndrome.
AB  - Family physicians should be able to recognize findings on physical examination
      and history that suggest the presence of a genetic syndrome to aid in the
      diagnosis and treatment of potentially affected patients, as well as subspecialty
      referral. General themes that can alert family physicians to the presence of
      genetic conditions include dysmorphic features that are evident on physical
      examination; multiple anomalies in one patient; unexplained neurocognitive
      impairment; and a family history that is suggestive of a hereditary disease. The
      presence of one obvious malformation should not limit the full evaluation,
      because additional, subtler findings will often be important in the differential
      diagnosis. Taking an accurate three-generation family history is invaluable when
      considering a genetic syndrome. Important elements include the age and sex of
      family members; when family members were affected by disease or when they died;
      the ethnic background; and if there is consanguinity. Genetic subspecialists can
      assist family physicians in diagnosis, suggest additional testing and referrals
      if warranted, help direct medical care, and provide counseling for affected
      patients and their families.

PMID- 23113463
TI  - Top 20 research studies of 2011 for primary care physicians.
AB  - In 2011, through regular surveillance of more than 100 English-language research
      journals, a group of seven clinicians identified approximately 250 studies with
      the potential to improve the practice of primary care physicians and the outcomes
      of patients (designated as POEMs [patient-oriented evidence that matters]). Using
      a validated tool, Canadian primary care physicians have been rating the relevance
      of each POEM as they receive it in their e-mail. This article summarizes 20 of
      the most relevant, practice-changing POEMs from 2011 as determined by these
      raters. We believe this approach has greater relevance and validity than a
      subjective list of studies selected by experts or editors, because it is based on
      the actual ratings of practicing primary care physicians. These POEMs address
      topics that include how to best measure blood pressure, the lack of benefit of
      intensive glucose control, quantification of the benefit of statins for
      prevention of cardiac events, treatments for functional abdominal disorders, and
      management of low back pain.

PMID- 23113464
TI  - Milky white elbow.

PMID- 23113465
TI  - Demoralization: a precursor to physician burnout?

PMID- 23113467
TI  - The role of nonpharmacologic therapies for back pain.

PMID- 23113468
TI  - Quantitative dispersion analysis of inclusions in polymer composites.
AB  - The state of dispersion plays an important role on the performance of polymer
      nanocomposites. Dispersion is usually assessed based on the qualitative
      evaluation of microscopy micrographs. In this paper, a quantitative algorithm is
      introduced for analyzing the dispersion of inclusions in polymer composites using
      image analysis. In a binary image, on-pixels are considered as particle elements
      while off-pixels stand for matrix elements. To quantify the dispersion, the mean
      distance value between any matrix elements to their corresponding nearest
      neighboring particle element is measured. A dispersion index, DI, is then defined
      by comparing the image of interest with the associated uniformly dispersed case.
      Synthetic models were utilized to examine the sensitivity of the algorithm to
      various dispersity scenarios such as the effect of particle size, clustering, and
      cluster distribution. Optical micrographs of carbon nanotube modified epoxy with
      different states of dispersion were also employed to assess the applicability and
      functionality of the algorithm to real micrographs.

PMID- 23113469
TI  - 1-Alkyl- and (+/-)-1,2-dialkyl-2,3-dihydro-1,8-naphthyridin-4(1H)-ones by a
      tandem Michael-SNAr annulation reaction.
AB  - A tandem Michael-S(N)Ar annulation reaction has been developed for the synthesis
      of 1-alkyl and (+/-)-1,2-dialkyl-2,3-dihydro-1,8-naphthyridin-4(1H)-ones.
      Treatment of 1-(2-chloropyridin-3-yl)prop-2-en-1-one (R = H) or (E or Z)-1-(2
      chloropyridin-3-yl)but-2-en-1-one (R = CH3) with R'NH2 in DMF at 50  degrees C
      for 24 h provides 2,3-dihydro-1,8-naphthyridin-4(1H)-ones in 65-85% yields.
      Mechanistic studies suggest that the reaction sequence is initiated by Michael
      addition to the side chain enone.

PMID- 23113470
TI  - Response to pretransplant hypomethylating agents influences the outcome of
      allogeneic hematopoietic stem cell transplantation in adults with myelodysplastic
      syndromes.
AB  - This study describes a retrospective analysis on the transplant outcome of 56
      consecutive patients with myelodysplastic syndrome (MDS) according to their
      response to hypomethylating agents (HMA). While 2-yr disease-free survival (DFS)
      of patients who transformed to acute myeloid leukemia (n = 12) was 25%, that of
      the remaining patients with MDS according to response to HMA was 73.1%, 68.1%,
      50.0%, and 20.8% in G-COR (group of continuous response, n = 19), G-NoC (group of
      no change, n = 15), G-LOR (group of loss of response, n = 6), and G-DP (group of
      disease progression, n = 4), respectively. When dichotomized as G-COR/G-NoC
      versus G-LOR/G-DP, significantly different 2-yr DFS (71.0% vs. 33.3%; P = 0.004)
      and relapse (14.1% vs. 46.7%; P = 0.016) were demonstrated. On multivariate
      analysis, G-LOR/G-DP [hazard ratio (HR), 3.91; P = 0.008] and poor karyotype at
      transplantation (HR, 2.69; P = 0.017) were the significant predictors for poor
      DFS, as G-LOR/G-DP was for relapse (HR, 6.28; P = 0.011). DFS was significantly
      poor in patients with any of the two predictors in all MDS (81.5% vs. 34.9%; P =
      0.001) or higher-risk MDS (HrMDS) at the time of HMA (80.7% vs. 29.2%; P =
      0.005). G-COR showed a trend of better DFS compared with G-NoC among HrMDS (74.6%
      vs. 36.5%; P = 0.090). These results implicate the significance of response to
      HMA on hematopoietic stem cell transplantation (HSCT) outcomes and support the
      need for future study to verify the suggested strategy of proceeding to
      transplantation before LOR or DP, especially for HrMDS.

PMID- 23113472
TI  - Mortality among oral contraceptive users: an evolving story.

PMID- 23113473
TI  - Differences in the vaginal lactobacilli of postmenopausal women and influence of
      rectal lactobacilli.
AB  - OBJECTIVE: This study was undertaken to characterize the Lactobacillus spp.
      dominating the vaginal microbiota of healthy postmenopausal women and to
      determine the possible influence of rectal lactobacilli. METHODS: Sixty
      postmenopausal women aged 55-65 years without clinical signs of vaginal infection
      not receiving hormone replacement therapy were included in this cross-sectional
      observational study. Based on Gram-stained smears, 30 women with a normal vaginal
      flora (Nugent score 0) were included in Group 1, and 30 women with an
      intermediate vaginal flora characterized by an absence of vaginal lactobacilli
      (Nugent score 4) were included in Group 2. Vaginal and rectal smears were taken
      for molecular lactobacillus profiling using polymerase chain reaction and
      denaturing gradient gel electrophoresis. Diversity of vaginal and rectal
      lactobacilli in postmenopausal women was the main outcome measure. RESULTS: We
      noticed a minor interference of gut lactic acid bacteria on a normal vaginal
      microflora dominated by lactobacilli strains of the L. delbrueckii group. When
      the normal vaginal microflora is disturbed by depletion of lactobacilli, the gut
      may function as a reservoir for lactobacilli of the L. casei group, which then
      colonize the vagina. CONCLUSION: Our data indicate that rectal lactobacilli may
      affect the vaginal flora of postmenopausal women in the case of lactobacillary
      absence and help to maintain a normal vaginal microbiota.

PMID- 23113474
TI  - Using cognitive interviewing for the semantic enhancement of multilingual
      versions of personality questionnaires.
AB  - We discuss the use of cognitive interviewing with bilinguals as an integral part
      of cross-cultural adaptation of personality questionnaires. The aim is to
      maximize semantic equivalence to increase the likelihood of items maintaining the
      intended structure and meaning in the target language. We refer to this part of
      adaptation as semantic enhancement, and integrate cognitive interviewing within
      it as a tool for scrutinizing translations, the connotative meaning, and the
      psychological impact of items across languages. During the adaptation of a work
      based personality questionnaire from English to Arabic, Chinese (Mandarin), and
      Spanish, we cognitively interviewed 12 bilingual participants about 136 items in
      different languages (17% of all items), of which 67 were changed. A content
      analysis categorizing the reasons for amending items elicited 11 errors that
      affect 2 identified forms of semantic equivalence. We provide the resultant
      coding scheme as a framework for designing cognitive interviewing protocols and
      propose a procedure for implementing them. We discuss implications for theory and
      practice.

PMID- 23113475
TI  - Apigenin alleviates the symptoms of Staphylococcus aureus pneumonia by inhibiting
      the production of alpha-hemolysin.
AB  - Staphylococcus aureus is a common human pathogenic bacteria that can cause
      serious infections, including lethal staphylococcal pneumonia. The development of
      antimicrobial resistance has limited treatment options for this pathogen;
      consequently, novel antibiotics and strategies are urgently desired to combat
      these infections. In recent years, virulence factors secreted by pathogenic
      microorganisms have been developed as targets for drug discovery. Alpha
      hemolysin, a pore-forming cytotoxin that is secreted by most S. aureus strains,
      is essential for the pathogenesis of S. aureus pneumonia. In this study, we
      report that apigenin, a compound extracted from parsley that has no antimicrobial
      activity vs. S. aureus in vitro, can remarkably decrease the production of alpha
      hemolysin at low concentrations. When added to the A549 cells and S. aureus co
      culture system, apigenin protected A549 cells from alpha-hemolysin-mediated
      injury. Furthermore, in vivo tests indicated that apigenin alleviated injury of
      the lung tissue and decreased cytokine levels in the bronchoalveolar lavage fluid
      in the mouse model of S. aureus pneumonia.

PMID- 23113476
TI  - Cancer screening campaigns--getting past uninformative persuasion.

PMID- 23113477
TI  - Risk, responsibility, and generic drugs.

PMID- 23113478
TI  - A shift on "pay for delay"--reopening doors for pharmaceutical competition?

PMID- 23113479
TI  - Growing pains for the Medicare hospice benefit.

PMID- 23113480
TI  - Topical 0.5% ivermectin lotion for treatment of head lice.
AB  - BACKGROUND: The emergence of resistance to treatment complicates the public
      health problem of head-louse infestations and drives the need for continuing
      development of new treatments. There are limited data on the activity of
      ivermectin as a topical lousicide. METHODS: In two multisite, randomized, double
      blind studies, we compared a single application of 0.5% ivermectin lotion with
      vehicle control for the elimination of infestations without nit combing in
      patients 6 months of age or older. A tube of topical ivermectin or vehicle
      control was dispensed on day 1, to be applied to dry hair, left for 10 minutes,
      then rinsed with water. The primary end point was the percentage of index
      patients (youngest household member with >=3 live lice) in the intention-to-treat
      population who were louse-free 1 day after treatment (day 2) and remained so
      through days 8 and 15. RESULTS: A total of 765 patients completed the studies. In
      the intention-to-treat population, significantly more patients receiving
      ivermectin than patients receiving vehicle control were louse-free on day 2
      (94.9% vs. 31.3%), day 8 (85.2% vs. 20.8%), and day 15 (73.8% vs. 17.6%) (P<0.001
      for each comparison). The frequency and severity of adverse events were similar
      in the two groups. CONCLUSIONS: A single, 10-minute, at-home application of
      ivermectin was more effective than vehicle control in eliminating head-louse
      infestations at 1, 7, and 14 days after treatment. (Funded by Topaz
      Pharmaceuticals [now Sanofi Pasteur]; ClinicalTrials.gov numbers, NCT01066585 and
      NCT01068158.).

PMID- 23113481
TI  - Mumps outbreak in Orthodox Jewish communities in the United States.
AB  - BACKGROUND: By 2005, vaccination had reduced the annual incidence of mumps in the
      United States by more than 99%, with few outbreaks reported. However, in 2006, a
      large outbreak occurred among highly vaccinated populations in the United States,
      and similar outbreaks have been reported worldwide. The outbreak described in
      this report occurred among U.S. Orthodox Jewish communities during 2009 and 2010.
      METHODS: Cases of salivary-gland swelling and other symptoms clinically
      compatible with mumps were investigated, and demographic, clinical, laboratory,
      and vaccination data were evaluated. RESULTS: From June 28, 2009, through June
      27, 2010, a total of 3502 outbreak-related cases of mumps were reported in New
      York City, two upstate New York counties, and one New Jersey county. Of the 1648
      cases for which clinical specimens were available, 50% were laboratory-confirmed.
      Orthodox Jewish persons accounted for 97% of case patients. Adolescents 13 to 17
      years of age (27% of all patients) and males (78% of patients in that age group)
      were disproportionately affected. Among case patients 13 to 17 years of age with
      documented vaccination status, 89% had previously received two doses of a mumps
      containing vaccine, and 8% had received one dose. Transmission was focused within
      Jewish schools for boys, where students spend many hours daily in intense, face
      to-face interaction. Orchitis was the most common complication (120 cases, 7% of
      male patients >=12 years of age), with rates significantly higher among
      unvaccinated persons than among persons who had received two doses of vaccine.
      CONCLUSIONS: The epidemiologic features of this outbreak suggest that intense
      exposures, particularly among boys in schools, facilitated transmission and
      overcame vaccine-induced protection in these patients. High rates of two-dose
      coverage reduced the severity of the disease and the transmission to persons in
      settings of less intense exposure.

PMID- 23113482
TI  - Fracture risk and zoledronic acid therapy in men with osteoporosis.
AB  - BACKGROUND: Fractures in men are a major health issue, and data on the
      antifracture efficacy of therapies for osteoporosis in men are limited. We
      studied the effect of zoledronic acid on fracture risk among men with
      osteoporosis. METHODS: In this multicenter, double-blind, placebo-controlled
      trial, we randomly assigned 1199 men with primary or hypogonadism-associated
      osteoporosis who were 50 to 85 years of age to receive an intravenous infusion of
      zoledronic acid (5 mg) or placebo at baseline and at 12 months. Participants
      received daily calcium and vitamin D supplementation. The primary end point was
      the proportion of participants with one or more new morphometric vertebral
      fractures over a period of 24 months. RESULTS: The rate of any new morphometric
      vertebral fracture was 1.6% in the zoledronic acid group and 4.9% in the placebo
      group over the 24-month period, representing a 67% risk reduction with zoledronic
      acid (relative risk, 0.33; 95% confidence interval, 0.16 to 0.70; P=0.002). As
      compared with men who received placebo, men who received zoledronic acid had
      fewer moderate-to-severe vertebral fractures (P=0.03) and less height loss
      (P=0.002). Fewer participants who received zoledronic acid had clinical vertebral
      or nonvertebral fractures, although this difference did not reach significance
      because of the small number of fractures. Bone mineral density was higher and
      bone-turnover markers were lower in the men who received zoledronic acid (P<0.05
      for both comparisons). Results were similar in men with low serum levels of total
      testosterone. The zoledronic acid and placebo groups did not differ significantly
      with respect to the incidence of death (2.6% and 2.9%, respectively) or serious
      adverse events (25.3% and 25.2%). CONCLUSIONS: Zoledronic acid treatment was
      associated with a significantly reduced risk of vertebral fracture among men with
      osteoporosis. (Funded by Novartis Pharma; ClinicalTrials.gov number,
      NCT00439647.).

PMID- 23113483
TI  - Comparing local and regional variation in health care spending.
AB  - BACKGROUND: Wide geographic variation in health care spending has generated both
      concern about inefficiency and policy debate about geographic-based payment
      reform. Evidence regarding variation has focused on hospital referral regions
      (HRRs), which incorporate numerous local hospital service areas (HSAs). If there
      is substantial variation across local areas within HRRs, then policies focusing
      on HRRs may be poorly targeted. METHODS: Using prescription drug and medical
      claims data from a 5% random sample of Medicare beneficiaries from 2006 through
      2009, we compared variation in health care spending and utilization among 306
      HRRs and 3436 HSAs. We adjusted for beneficiary-level demographic
      characteristics, insurance status, and clinical characteristics. RESULTS: There
      was substantial local variation in health care (drug and nondrug) utilization and
      spending. Furthermore, many of the low-spending HSAs were located in high
      spending HRRs, and many of the high-spending HSAs were in low-spending HRRs. For
      drug spending, only 50.7% of the HSAs located within the borders of the highest
      spending quintile of HRRs were in the highest-spending quintile of HSAs;
      conversely, only 51.5% of the highest-spending HSAs were located within the
      borders of the highest-spending HRRs. Similar patterns were observed for nondrug
      spending. CONCLUSIONS: The effectiveness of payment reforms in reducing
      overutilization while maintaining access to high-quality care depends on the
      effectiveness of targeting. Our analysis suggests that HRR-based policies may be
      too crudely targeted to promote the best use of health care resources. (Funded by
      the Institute of Medicine and others.).

PMID- 23113484
TI  - Two hundred years of progress in the practice of midwifery.

PMID- 23113485
TI  - Images in clinical medicine. Dermoscopy of nits and pseudonits.

PMID- 23113486
TI  - Clinical problem-solving. A complex cause of pleuritic chest pain.

PMID- 23113487
TI  - Topical ivermectin--a step toward making head lice dead lice?

PMID- 23113488
TI  - Hunting down huntingtin.

PMID- 23113489
TI  - How much would you give to save a dying bird? Patient advocacy and biomedical
      research.

PMID- 23113491
TI  - n-3 fatty acids and cardiovascular outcomes in dysglycemia.

PMID- 23113492
TI  - n-3 fatty acids and cardiovascular outcomes in dysglycemia.

PMID- 23113494
TI  - Basal insulin and cardiovascular and other outcomes.

PMID- 23113495
TI  - Basal insulin and cardiovascular and other outcomes.

PMID- 23113496
TI  - Basal insulin and cardiovascular and other outcomes.

PMID- 23113497
TI  - Basal insulin and cardiovascular and other outcomes.

PMID- 23113498
TI  - Targeting epigenetic readers in cancer.

PMID- 23113500
TI  - Treatment of older patients with mantle-cell lymphoma.

PMID- 23113501
TI  - Denosumab for post-transplantation hypercalcemia in osteopetrosis.

PMID- 23113505
TI  - Images in clinical medicine. Ochronosis.

PMID- 23113507
TI  - Oligothienyl-BODIPYs: red and near-infrared emitters.
AB  - The synthesis of unsymmetrical 3,5-dioligothienyl-BODIPY derivatives and their
      optical and redox properties are reported. The key step is the monobromination of
      the 2,6-dimethyl-3,5-dithienyl-BODIPY at the alpha position of the thiophene
      moiety. The additional thiophene modules are attached by palladium-catalyzed
      cross-coupling reactions. Increasing the number of modules on each side of the
      BODIPY core progressively shifts the absorption to 677 nm and the emission to 769
      nm.

PMID- 23113506
TI  - Different parasite inocula determine the modulation of the immune response and
      outcome of experimental Trypanosoma cruzi infection.
AB  - During infection, the host response develops effector mechanisms to combat the
      parasite. However, this response can become uncontrolled or regulated by
      mechanisms that modulate the inflammatory reaction. The number of parasites that
      infects the host, such as trypomastigotes in Chagas disease, may also influence
      immune activation and disease pathology. We evaluated the inflammation and immune
      regulation that follows Trypanosoma cruzi infection with low (300), intermediate
      (3000) or high (30000) parasite loads. Our results showed that the load of
      parasite inoculum influenced disease outcome: the higher the number of parasites
      in the inoculum, the lower were the survival rates. There was a strong
      association between parasitism and inflammatory infiltrate in the heart and the
      parasite inoculum determined cytokine interplay in this tissue, as shown by
      increased interferon-gamma, tumour necrosis factor-alpha, interleukin-17 (IL-17)
      and IL-23 in the 300 and 30000 inoculum groups, higher IL-4 and IL-10 in the
      intermediate-inoculum mice, and elevated IL-6 production in the heart of mice in
      the 3000 and 30000 groups. The number of T cells and antigen-presenting cells was
      augmented in the infected groups, especially for the splenic CD4(+) CD25(+)
      regulatory T cells expressing CD45RB(low) , GITR, PD-1 and FoxP3 in the group
      with the highest inoculum. Interestingly, these mice also presented an apparent
      decrease in CD4(+) CD25(+) FoxP3(+) cells in the cardiac infiltrate, in contrast
      to the intermediate inoculum group, which showed elevated numbers of these
      regulatory leucocytes in the heart. Finally, our results demonstrated that
      parasite load during T. cruzi infection is linked to the response pattern that
      will result in parasite/inflammation control or tissue damage.

PMID- 23113510
TI  - Evaluation of bacterial microleakage of root canals irrigated with different
      irrigation solutions and KTP laser system.
AB  - OBJECTIVE: The aim of this study was to evaluate bacterial microleakage of the
      root canals irrigated with different irrigation solutions and the potassium
      titanyl-phosphate (KTP) laser system and filled with gutta-percha and AH26 root
      canal sealer. In addition, the effect of the irrigation solutions on dentin
      surface was evaluated with a scanning electron microscope (SEM). BACKGROUND DATA:
      A few studies have reported that KTP laser has the capacity to remove the smear
      layer. Many researchers have demonstrated that propolis has a bactericidal
      effect. Both are important effects on root canal treatments. MATERIALS AND
      METHODS: One hundred and twenty single-root single-canal mandibular premolar
      teeth were used for this study. The root canals were prepared by Dentaport Root
      ZX and ProTaper rotary instruments with the crown-down technique. The specimens
      were randomly divided into five groups of 20 teeth each. Each group was irrigated
      with 17% ethylenediaminetetraacetic acid (EDTA), 20% propolis, 2.5% sodium
      hypochlorite (NaOCl), 2% chlorhexidine gluconate (CHX), and KTP laser,
      respectively. A total of 20 teeth were used as controls-10 positive controls and
      10 negative controls-which were irrigated with distilled water. The root canals
      were filled with gutta-percha and AH-26. The external surfaces of specimens were
      covered with three layers of nail varnish except the apical third. The teeth were
      inserted into Eppendorf plastic tubes and suspended in glass bottles containing
      sterile broth. All specimens were inoculated every 5 days with Enterococcus
      faecalis. The contamination onset time was continuously recorded, as turbidity
      was the first indication of contamination in a period of 30 days. RESULTS: All
      statistical analysis was performed using the SPSS for Windows version 15.0
      software. A chi(2) test was computed and the statistical significance was set at
      p<0.05. The controls behaved as expected. CONCLUSIONS: This study showed that
      different irrigation solutions and KTP laser allowed microleakage of E. faecalis.

PMID- 23113511
TI  - Promoting wound healing in minor recurrent aphthous stomatitis by non-thermal,
      non-ablative CO(2) laser therapy: a pilot study.
AB  - BACKGROUND AND OBJECTIVE: This randomized controlled clinical trial (RCT) was
      designed to evaluate the effects of non-thermal, non-ablative CO(2) laser therapy
      (NACLT) to promote wound healing in minor recurrent aphthous stomatitis (miRAS).
      STUDY DESIGN/MATERIALS AND METHODS: Ten patients with 20 minor aphthous ulcers
      completed this study. Each patient had two discrete aphthous ulcers that had
      developed within 72 h before enrollment. One of the ulcers was randomly allocated
      to be treated with NACLT and the other one served as placebo. Before laser
      irradiation, a layer of transparent, non-anesthetic oral gel with high water
      content was placed on the laser and placebo lesions both. The CO(2) laser device
      was operated using 1 W power in defocused continuous mode, scanning rapidly over
      the lesion. The placebo lesion was irradiated with the same laser, but with an
      inactive probe. The healing times of the lesions were recorded by a blinded
      physician. RESULTS: The healing period was significantly shorter in ulcers
      treated by NACLT than in those treated with placebo (p=0.02). The process was not
      painful and anesthesia was not required. There were no visible side effects after
      NACLT and during follow-up periods. CONCLUSIONS: The results of this RCT suggest
      that single session of NACLT could be used to promote wound healing in minor
      aphthous ulcers, with no visible side effects.

PMID- 23113514
TI  - Triage follows deep cuts: public health authorities examining services following
      budget reductions.

PMID- 23113512
TI  - Thulium laser vaporesection versus transurethral electrovaporization of the
      prostate in high-risk patients with benign prostatic hyperplasia.
AB  - OBJECTIVE: The purpose of this study was to compare the safety and efficacy of
      the thulium laser vaporesection and transurethral electrovaporization of the
      prostate for the treatment of high-risk patients with benign prostatic
      hyperplasia. BACKGROUND DATA: From September 2009 to March 2011, 98 consecutive
      patients with symptomatic bladder outlet obstruction caused by benign prostatic
      hyperplasia received either thulium laser vaporesection of the prostate (n=42) or
      transurethral electrovaporization of the prostate (n=56) at our institution.
      MATERIALS AND METHODS: Functional follow-up included measurement of International
      Prostate Symptom Score, quality of life score, maximal urinary flow rate, and
      post-voiding residual urine volume. All complications were recorded. RESULTS:
      Thulium laser vaporesection of the prostate was slightly superior to
      transurethral electrovaporization of the prostate in catheterization time (2.1+/
      0.9 vs. 4.5+/-1.3 days, p<0.0001) and postoperative hospital stay (4.4+/-1.8 vs.
      6.6+/-2.0 days, p<0.0001). Within the observation period, both groups had a
      significant improvement from baseline in subjective or objective success rates;
      however, no significant difference was found between the two groups. Peri- and
      postoperative complications were fewer in the thulium laser group. CONCLUSIONS:
      Thulium laser vaporesection of the prostate is as effective as transurethral
      electrovaporization of the prostate in managing high-risk patients, with
      sufficient tissue ablation and acceptable hemostasis, and has the advantage of
      less morbidity and shorter catheter time and postoperative hospital stay.

PMID- 23113515
TI  - Antirabies antibody titers without vaccination.

PMID- 23113516
TI  - What is your diagnosis? Pathological fracture of P3.

PMID- 23113517
TI  - Diagnostic imaging in veterinary dental practice.

PMID- 23113518
TI  - ECG of the month. Multiform ventricular tachycardia.

PMID- 23113519
TI  - Animal behavior case of the month: thunderstorm phobia.

PMID- 23113520
TI  - Pathology in practice: Aspergillus flavus mycosis.

PMID- 23113521
TI  - Pathology in practice: ethylene glycol toxicosis.

PMID- 23113522
TI  - Evaluation of a ketamine-propofol drug combination with or without
      dexmedetomidine for intravenous anesthesia in cats undergoing ovariectomy.
AB  - OBJECTIVE: To evaluate the use of a ketamine-propofol combination, with or
      without dexmedetomidine, in cats undergoing ovariectomy and to assess Heinz body
      formation following administration of these drugs. DESIGN: Randomized clinical
      trial. ANIMALS: 15 client-owned female cats. PROCEDURES: Anesthesia was induced
      with a ketamine (2.0 mg/kg [0.91 mg/lb])-propofol (2.0 mg/kg) combination with (n
      = 7) or without (8) dexmedetomidine (0.003 mg/kg [0.0013 mg/lb]) and was
      maintained via continuous IV infusion of a 1:1 ketamine-propofol combination
      (administration rate for each drug, 10.0 mg/kg/h [4.54 mg/lb/h]). Cats underwent
      ovariectomy; duration of infusion was 25 minutes. Physiologic variables were
      measured at predetermined time points. Heinz bodies were quantified via
      examination of blood smears. Numeric scales were used to assess quality of
      recovery, degree of sedation, and signs of pain after surgery. RESULTS: The
      ketamine-propofol group had a significantly higher mean heart rate at several
      time points during drug infusion, a significantly shorter time from the end of
      infusion to extubation (7 vs 29 minutes), and significantly lower sedation scores
      for the first hour after surgery than did the ketamine-propofol-dexmedetomidine
      group. Other variables were similar between groups; recovery was smooth, and
      anesthesia and postoperative analgesia were deemed adequate for all cats. The
      number of RBCs with Heinz bodies was not increased after surgery, compared with
      values immediately after anesthetic induction. CONCLUSIONS AND CLINICAL
      RELEVANCE: Total IV anesthesia with a ketamine-propofol combination, with or
      without dexmedetomidine, appeared to be effective in healthy cats. These short
      term infusions produced smooth recovery and adequate analgesia during the
      postoperative period.

PMID- 23113523
TI  - Caregiver placebo effect for dogs with lameness from osteoarthritis.
AB  - OBJECTIVE: To document the caregiver placebo effect in owners and veterinarians
      of dogs with lameness from osteoarthritis. DESIGN: Prospective, randomized,
      double-blinded, placebo-controlled, multicenter clinical trial. ANIMALS: 58 dogs
      with lameness secondary to osteoarthritis. PROCEDURES: Dogs enrolled in the
      placebo arm of an FDA-approved study were evaluated to determine the relationship
      between subjective (caregiver responses) and objective (force platform gait
      analysis) patient outcome measures. RESULTS: A caregiver placebo effect for
      owners evaluating their dog's lameness occurred 39.7% of the time. A caregiver
      placebo effect occurred 44.8% of the time when veterinarians examined dogs for
      lameness at a walk, 44.8% of the time when veterinarians examined dogs for
      lameness at a trot, and 43.1% of the time when veterinarians evaluated dogs for
      signs of pain on palpation of the joint. This effect was significantly enhanced
      with time. Mean ground reaction forces (GRFs) remained unchanged for dogs during
      treatment with the placebo. Individually, of 58 dogs, 5 had GRFs that worsened by
      >= 5% over 42 days, 7 had GRFs that improved by >= 5% over 42 days, and 46 had
      GRFs that remained unchanged. CONCLUSIONS AND CLINICAL RELEVANCE: A caregiver
      placebo effect was common in the evaluation of patient response to treatment for
      osteoarthritis by both pet owners and veterinarians. Force platform gait analysis
      was an unbiased outcome measure for dogs with lameness from osteoarthritis. A
      caregiver placebo effect should be considered when interpreting owner and
      veterinary reports of patient response to treatment.

PMID- 23113524
TI  - Prevalence of serum antibody titers against feline panleukopenia virus, feline
      herpesvirus 1, and feline calicivirus in cats entering a Florida animal shelter.
AB  - OBJECTIVE: To determine the proportion of cats entering a Florida animal shelter
      with serum antibody titers against feline panleukopenia virus (FPV), feline
      herpesvirus 1 (FHV1), and feline calicivirus (FCV) and to identify factors
      associated with seropositivity. DESIGN: Cross-sectional study. ANIMALS: 347 cats
      admitted to a Florida animal shelter. PROCEDURES: Within 24 hours after admission
      to the animal shelter, blood samples were collected from all cats >= 8 weeks of
      age. Serum antibody titers against FPV were determined via a hemagglutination
      inhibition assay, and those against FHV1 and FCV were determined via virus
      neutralization assays. Age, sex, environment (urban or rural), source (stray or
      previously owned), evidence of previous caregiving, health status (healthy or not
      healthy), and outcome (adoption, transfer, return to owner, or euthanasia) were
      evaluated as potential factors associated with antibody seropositivity. RESULTS:
      Of 347 cats, 138 (39.8%), 38 (11.0%), and 127 (36.6%) had antibody titers >= 40,
      >= 8, and >= 32 (ie, seropositive) against FPV, FHV1, and FCV, respectively.
      Factors associated with seropositivity included being neutered, age >= 6 months,
      and being relinquished by an owner. On multivariable analysis, health status at
      shelter admission, environment, vaccination at shelter admission, and outcome
      were not associated with seropositivity. CONCLUSIONS AND CLINICAL RELEVANCE: Most
      cats were seronegative for antibodies against FPV, FHV1, and FCV at the time of
      admission to an animal shelter. These findings supported current guidelines that
      recommend vaccination of all cats immediately after admission to animal shelters,
      regardless of the source or physical condition.

PMID- 23113525
TI  - Parathyroid hormone concentration in geriatric cats with various degrees of renal
      function.
AB  - OBJECTIVE: To determine whether cats in the nonazotemic stages of chronic kidney
      disease have increased plasma parathyroid hormone (PTH) concentrations as a
      compensatory physiologic mechanism to maintain plasma phosphate concentration
      within the reference interval. DESIGN: Prospective longitudinal study. ANIMALS:
      118 client-owned geriatric cats with various degrees of renal function.
      PROCEDURES: For each cat, a blood sample was obtained for plasma biochemical
      analysis and determination of plasma PTH concentration, and a urine sample was
      obtained for determination of urine specific gravity at study entry (baseline)
      and after 12 months. For a subset of 30 cats, plasma calcitriol concentration was
      determined at baseline. Cats were categorized into 1 of 3 groups on the basis of
      kidney function at the end of 12 months. At baseline and after 12 months, plasma
      concentrations of variables associated with calcium homeostasis were compared
      between the 3 groups and also within groups over time. Multivariable linear
      regression was used to identify variables associated with plasma PTH
      concentration. RESULTS: Plasma PTH concentration was significantly increased in
      cats that developed azotemia, compared with PTH concentration in cats that
      remained nonazotemic, and PTH concentration increased before changes in plasma
      calcium and phosphate concentrations were detected. A moderate positive
      association between plasma calcitriol and PTH concentrations was identified.
      Plasma PTH concentration was associated with age and plasma urea, creatinine, and
      total calcium concentrations in the final multivariable model. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results suggested that renal secondary hyperparathyroidism
      can develop prior to azotemia in cats, even in the absence of hyperphosphatemia
      and hypocalcemia.

PMID- 23113526
TI  - Evaluation of hemostatic and fibrinolytic markers in dogs with ascites
      attributable to right-sided congestive heart failure.
AB  - OBJECTIVE: To determine whether dogs with ascites secondary to right-sided
      congestive heart failure (CHF) have bleeding disorders associated with
      hypofibrinogenemia and discordant plasma fibrin-fibrinogen degradation products
      (FDPs) and D-dimer assay results (ie, a circulating concentration of FDPs higher
      than the reference range and a circulating concentration of D-dimer within the
      reference range). DESIGN: Retrospective case-control study. ANIMALS: 80 client
      owned dogs. PROCEDURES: Dogs with ascites secondary to right-sided CHF (group 1;
      n = 20), unhealthy dogs without cardiac disease (group 2; 40), and dogs with left
      sided CHF (group 3; 20) were included in the study. Urine bile acids-to
      creatinine concentration ratios were calculated as a marker of liver function.
      Differences among groups regarding coagulation profile analysis results and
      prevalence of discordant FDPs and D-dimer assay results were determined. RESULTS:
      No significant differences were detected among the 3 groups regarding urine bile
      acids-to-creatinine concentration ratios. Plasma fibrinogen concentration was
      significantly lower for group 1 versus groups 2 or 3. Prevalence of discordant
      FDPs and D-dimer assay results was significantly higher for group 1 versus groups
      2 or 3. Eighteen group 1 dogs had discordant FDPs and D-dimer assay results. Ten
      of these dogs had concurrent hypofibrinogenemia, 2 of which had clinical signs of
      bleeding. Only 10 dogs in groups 2 or 3 had discordant FDPs and D-dimer assay
      results; none of these dogs had hypofibrinogenemia or clinical signs of bleeding.
      CONCLUSIONS AND CLINICAL RELEVANCE: Dogs with right-sided CHF and ascites may be
      at increased risk for primary hyperfibrinogenolysis (ie, hypofibrinogenemia and
      discordant FDPs and D-dimer assay results).

PMID- 23113527
TI  - Evaluation of heart murmurs in chinchillas (Chinchilla lanigera): 59 cases (1996
      2009).
AB  - OBJECTIVE: To determine the prevalence of heart murmurs in chinchillas
      (Chinchilla lanigera) and determine whether heart murmurs were associated with
      cardiac disease. DESIGN: Retrospective multi-institutional case series. ANIMALS:
      260 chinchillas. PROCEDURES: Medical records of all chinchilla patients evaluated
      at the Tufts University Foster Hospital for Small Animals between 2001 and 2009,
      the University of California-Davis William R. Pritchard Veterinary Medical
      Teaching Hospital between 1996 and 2009, and the University of Wisconsin
      Veterinary Medical Teaching Hospital between 1998 and 2009 were reviewed.
      RESULTS: Prevalence of heart murmurs was 23% (59/260). Of 15 chinchillas with
      heart murmurs that underwent echocardiography, 8 had echocardiographic
      abnormalities, including dynamic right ventricular outflow tract obstruction,
      mitral regurgitation, hypertrophy of the left ventricle, tricuspid regurgitation,
      and hypovolemia. Echocardiographic abnormalities were approximately 29 times as
      likely (OR, 28.7) to be present in chinchillas with a murmur of grade 3 or higher
      than in chinchillas without a murmur. CONCLUSIONS AND CLINICAL RELEVANCE: Results
      suggested that heart murmurs are common in chinchillas and that chinchillas with
      heart murmurs often have echocardiographic abnormalities, with valvular disease
      being the most common. On the basis of these results, we believe that
      echocardiography should be recommended for chinchillas with heart murmurs,
      especially older chinchillas with murmurs of grade 3 or higher. Further
      prospective studies are needed to accurately evaluate the prevalence of cardiac
      disease in chinchillas with heart murmurs.

PMID- 23113528
TI  - 2,8-Dihydroxyadenine uroliths in a dog.
AB  - CASE DESCRIPTION: A 43-kg (95-lb) 4-year-old neutered male mixed-breed dog was
      evaluated because of a 2-day history of dysuria. CLINICAL FINDINGS: Radiography
      and ultrasonography revealed hydronephrosis, hydroureter, and radiolucent,
      hyperechoic uroliths in the right kidney and ureter and the urinary bladder.
      Serum bile acids concentration was within the reference interval. TREATMENT AND
      OUTCOME: The uroliths in the bladder and right ureter were surgically removed and
      submitted for analysis. They were initially identified as urate uroliths;
      however, results of further analysis indicated uroliths were composed of 2,8
      dihydroxyadenine (2,8-DHA), and 2,8-DHA was identified in a urine sample of the
      dog. Allopurinol was prescribed for the dog, and a purine-restricted diet was
      recommended. CLINICAL RELEVANCE: 2,8-DHA uroliths are extremely rare in humans
      and dogs. Such uroliths may be underdiagnosed in humans because of variability of
      clinical signs and difficulty in differentiating 2,8-DHA and urate uroliths and
      crystalluria. Uroliths composed of 2,8-DHA may be misdiagnosed as urate uroliths
      in dogs.

PMID- 23113529
TI  - Response to injection of the navicular bursa with corticosteroid and hyaluronan
      following high-field magnetic resonance imaging in horses with signs of navicular
      syndrome: 101 cases (2000-2008).
AB  - OBJECTIVE: To determine treatment outcome on the basis of pathological changes
      identified on MRI and lameness duration in horses with navicular syndrome that
      underwent injection of corticosteroid and hyaluronan into the navicular bursa.
      DESIGN: Retrospective case series. ANIMALS: 101 horses with navicular syndrome.
      PROCEDURES: Medical records of horses with signs of navicular syndrome evaluated
      between January 2000 and December 2008 were reviewed. Data on signalment, use of
      the horse, history, affected limbs, duration of lameness, findings on lameness
      examination, radiographic findings, MRI findings, treatment, and outcome were
      collected from the medical records. Follow-up information was obtained a minimum
      of 10 months after navicular bursa injection. RESULTS: Following navicular bursa
      injection, 76 of 101 (75%) horses returned to their intended use for a mean of
      9.66 months, and 35 (35%) were sound at follow-up. Horses that had been lame for
      < 6 months before treatment were significantly more likely to return to their
      intended use, have a longer positive response to treatment, and be sound at
      follow-up, compared with horses that had a longer lameness history. Horses with
      primary deep digital flexor (DDF) tendonitis responded best to navicular bursa
      injection with rest and rehabilitation, followed by horses with navicular
      bursitis and horses with DDF tendonitis and adhesions to the collateral
      sesamoidean ligament of the distal sesamoid (navicular) bone. Horses with scar
      tissue in the proximal portion of the navicular bursa, adhesions from the
      navicular bone to the DDF tendon, or multiple abnormalities did not respond as
      well to treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Response to navicular
      bursa injection with corticosteroid and hyaluronan in horses with navicular
      syndrome was dependent on the disease process detected on MRI and duration of
      lameness.

PMID- 23113530
TI  - Implementation and validation of probabilistic models of the anterior
      longitudinal ligament and posterior longitudinal ligament of the cervical spine.
AB  - The objective of this investigation was to develop probabilistic finite element
      (FE) models of the anterior longitudinal ligament (ALL) and posterior
      longitudinal ligament (PLL) of the cervical spine that incorporate the natural
      variability of biological specimens. In addition to the model development, a
      rigorous validation methodology was developed to quantify model performance.
      Experimental data for the geometry and dynamic properties of the ALL and PLL were
      used to create probabilistic FE models capable of predicting not only the mean
      dynamic relaxation response but also the observed experimental variation of that
      response. The probabilistic FE model uses a quasilinear viscoelastic material
      constitutive model to capture the time-dependent behaviour of the ligaments. The
      probabilistic analysis approach yields a statistical distribution for the model
      predicted response at each time point rather than a single deterministic quantity
      (e.g. ligament force) and that response can be statistically compared to
      experimental data for validation. A quantitative metric that compares the
      cumulative distribution functions of the experimental data and model response is
      computed for both the ALL and PLL throughout the time histories and is used to
      quantify model performance. 

PMID- 23113531
TI  - Effects of a shoot training programme with a reduced hoop diameter rim on free
      throw performance and kinematics in young basketball players.
AB  - The present paper investigated the effects of a shoot training programme with a
      reduced hoop diameter (0.35 m) rim on kinematics and performance of basketball
      free-throws. Eighteen young male basketball players were divided into control
      (CG, n = 9) and experimental (EG, n = 9) groups. Both groups undertook a 10-week
      training programme comprising two training sessions per week. Under fatigued
      conditions, each participant shot 150 free-throws in each training session, with
      the CG using a standard rim, and the EG a smaller rim. All other training was
      identical between groups. Ball release parameters, player's kinematics and mean
      of successful free-throws (out of 150 attempts) were determined for each
      participant, before and after completion of the training programme. Following
      training, a significant increase (P < 0.05) in ball release angle, speed and
      height and in shoulder joint angle at release (P < 0.01) was observed for the EG.
      Both the CG (P < 0.001) and the EG (P < 0.0001) showed an increase in the number
      of successful free throws, although the increase was greater (P < 0.05) for the
      EG (22.7 +/- 6.4 free throws) than for the CG (14.6 +/- 7.8 free throws). We
      conclude that training with a reduced rim significantly improves free-throw
      performance in young basketball players.

PMID- 23113532
TI  - Lack of association between polymorphisms from genome-wide association studies
      and tuberculosis in the Chinese population.
AB  - Genome-wide association studies (GWAS) have identified rs4331426 and rs2057178 as
      being associated with tuberculosis (TB) in African populations. Both are common
      single nucleotide polymorphisms (SNPs) in Africans, but they are much rarer in
      Eurasian populations. In order to corroborate these results, we carried out a
      case-control study in the Chinese population; these 2 SNPs were genotyped in 600
      pulmonary TB patients and 618 healthy controls. The results showed that neither
      of the SNPs was associated with TB, even after stratification by gender, age, and
      smear status. Considering the limitation of poor coverage of variations in
      commercial available genotyping platforms in African populations, further GWAS
      should be conducted in other populations such as Indian and Chinese. Moreover,
      future genetic studies on host susceptibility to TB need to take into account all
      the variables, including host, environment, pathogen, and interactions.

PMID- 23113533
TI  - Series of dicyanamide-interlaced assembly of zinc-Schiff-base complexes: crystal
      structure and photophysical and thermal studies.
AB  - Four new dicyanamide (dca) bridged multinuclear Zn(II)-Schiff-base complexes,
      {[Zn2L(1)(MU1,5-dca)dca].CH3OH}2 (1), [Zn2L(2)(MU1,5-dca)dca]n (2),
      [Zn3L(3)2(MU1,5-dca)2]n (3), and [(ZnL(4))2Zn(MU1,5-dca)dca]n (4), have been
      synthesized using four different Schiff bases L(1)H2 = N,N(/)-bis(3
      methoxysalicylidenimino)-1,3-diaminopentane, L(2)H2 = N,N'-bis(5-bromo-3
      methoxysalicylidenimino)-1,3-diaminopropane, L(3)H2 = N,N'-bis(5
      bromosalicylidenimino)-1,3-diaminopropane, and L(4)H2 = N,N'-bis(5
      chlorosalicylidenimino)-1,3-diaminopropane and NaN(CN)2 in order to extend the
      metal-ligand assembly. The directional properties of linear end-to-end bridging
      dca ligands have resulted in different metal ion connectivities leading to unique
      variety of templates in each of the complexes. All the ligands and complexes have
      been characterized by microanalytical and spectroscopic techniques. The
      structures of the complexes have been conclusively determined by single crystal X
      ray diffraction studies. Thermogravimetric analyses have been performed to
      investigate the thermal stability of the metal-organic frameworks. Finally, the
      photoluminescence properties of the complexes as well as their respective ligands
      have been investigated with a comparative approach. 

PMID- 23113534
TI  - Investigating the prevalence of transfusion transmission of Plasmodium within a
      hyperendemic blood donation system.
AB  - BACKGROUND: Prevention of transfusion-transmitted malaria in at-risk children and
      pregnant women in endemic areas with inexpensive chloroquine is no longer
      effective due to widespread drug resistance. There is an urgent need for devising
      new strategies for transfusion malarial safety. We investigated the frequency of
      transfusion transmission of malaria within the Ghanaian blood donation system
      using blood donations from 106 asymptomatic adult Ghanaian blood donors. STUDY
      DESIGN AND METHODS: Paired samples from 106 blood donations and recipients
      (before and after transfusion) were tested for anti-merozoite surface protein-1/2
      using the commercial Lab21 malaria enzyme immunoassay (EIA), four antigen
      specific in-house EIAs, and Plasmodium lactate dehydrogenase (pLDH) EIA.
      Additionally, Plasmodium DNA was screened for using a species-specific nested
      polymerase chain reaction (PCR) and a Pan-Plasmodium quantitative PCR. Donor
      recipient parasite identity was defined by two concordant genotyping strategies.
      RESULTS: Plasmodium antibody prevalence was 100% in both donors and recipients,
      with at least one antigen. Parasitemia prevalence was 54.7% in both donors and
      recipients with median levels of 20 and 5.3 copies/MUL, respectively, the
      difference being correlated to age (p = 0.0001). Multiple species infections were
      frequent (8.5%). Twenty-four units of parasitemic blood were transfused to
      nonparasitemic recipients, of which 10 (41.7%) became infected after transfusion.
      Molecular genotyping with 13 distinct markers (antigenic genes and microsatellite
      loci) identified three to nine parasitemic recipients after transfusion with
      level of allelic identity suggesting 14% to 28% definite or possible transfusion
      related parasitemia. CONCLUSION: None of the currently available screening assays
      appear suitable to minimize transfusion malaria without compromising the blood
      supply in endemic areas.

PMID- 23113535
TI  - Plant hormones as signals in arbuscular mycorrhizal symbiosis.
AB  - Arbuscular mycorrhizal (AM) fungi are non-specific symbionts developing mutual
      and beneficial symbiosis with most terrestrial plants. Because of the obligatory
      nature of the symbiosis, the presence of the host plant during the onset and
      proceeding of symbiosis is necessary. However, AM fungal spores are able to
      germinate in the absence of the host plant. The fungi detect the presence of the
      host plant through some signal communications. Among the signal molecules, which
      can affect mycorrhizal symbiosis are plant hormones, which may positively or
      adversely affect the symbiosis. In this review article, some of the most recent
      findings regarding the signaling effects of plant hormones, on mycorrhizal fungal
      symbiosis are reviewed. This may be useful for the production of plants, which
      are more responsive to mycorrhizal symbiosis under stress.

PMID- 23113537
TI  - First-principles calculation of NMR parameters using the gauge including
      projector augmented wave method: a chemist's point of view.

PMID- 23113538
TI  - An osmium(III)/osmium(V) redox couple generating Os(V)(O)(OH) center for cis-1,2
      dihydroxylation of alkenes with H2O2: Os complex with a nitrogen-based
      tetradentate ligand.
AB  - For the synthesis of the 1,2-diols, cis-1,2-dihydroxylation of alkenes catalyzed
      by osmium(VIII) tetroxide (OsO(4)) is a powerful method. However, OsO(4) is quite
      toxic due to its highly volatile and sublimable nature. Thus, the development of
      alternative catalysts for cis-1,2-dihydroxylation of alkenes is highly
      challenging. Our approach involves the use of a nitrogen-based tetradentate
      ligand, tris(2-pyridylmethyl)amine (tpa), for an osmium center to develop a new
      osmium catalyst and hydrogen peroxide (H(2)O(2)) as a cheap and environmentally
      benign oxidant. The new Os-tpa complex acts as a very efficient turnover catalyst
      for syn-selective dihydroxylation of various alkenes (turnover number ~1000) in
      aqueous media, and H(2)O(2) oxidant is formally incorporated into the products
      quantitatively (100% atom efficiency). The reaction intermediates involved in the
      catalytic cycle have been isolated and characterized crystallographically as
      [Os(III)(OH)(H(2)O)(tpa)](2+) and [Os(V)(O)(OH)(tpa)](2+) complexes. The observed
      syn-selectivity, structural characteristics of the intermediates, and kinetic
      studies have suggested a concerted [3 + 2]-cycloaddition mechanism between
      [Os(V)(O)(OH)(tpa)](2+) and alkenes, which is strongly supported by DFT
      calculations.

PMID- 23113536
TI  - The sphingosine kinase inhibitor 2-(p-hyroxyanilino)-4-(p-chlorophenyl)thiazole
      reduces androgen receptor expression via an oxidative stress-dependent mechanism.
AB  - BACKGROUND AND PURPOSE: Sphingosine kinase catalyses the formation of sphingosine
      1-phosphate and is linked with androgen receptor signalling in prostate cancer
      cells. Therefore, we investigated the effect of sphingosine kinase inhibitors on
      androgen receptor expression. EXPERIMENTAL APPROACH: Androgen-sensitive LNCaP
      cells were treated with SKi (2-(p-hydroxyanilino)-4-(p-chlorophenyl)thiazole),
      which inhibits sphingosine kinases 1 and 2 activity, and the effect on androgen
      receptor expression was measured. KEY RESULTS: Treatment of cells with SK1
      inhibitors reduced the expression of the androgen receptor and prostate-specific
      antigen, while (R)-FTY720 methyl ether (a sphingosine-kinase-2-selective
      inhibitor), at a concentration that eliminates sphingosine kinase 2 from cells,
      had no significant effect on androgen receptor expression. The effect of SKi on
      androgen receptor expression was independent of the SKi-induced proteasomal
      degradation of SK1 and was post translational, although androgen receptor mRNA
      transcript was reduced. Fumonisin B1 (a ceramide synthase inhibitor) also failed
      to reverse the effect of SKi on androgen receptor expression, thereby excluding a
      role for ceramide derived from the salvage pathway. The effect of SKi on androgen
      receptor expression was reversed by N-acetylcysteine, which was used to scavenge
      reactive oxygen species. CONCLUSION AND IMPLICATIONS: Inhibition of sphingosine
      kinase 1 activity abrogates androgen receptor signalling via an oxidative stress
      induced, p53-independent mechanism in prostate cancer cells. Therefore, SK1
      inhibitors may offer therapeutic potential in promoting the removal of AR
      receptors from prostate cancer cells, resulting in an increased efficacy, which
      is likely to be superior to inhibitors that simply reversibly inhibit AR
      signalling.

PMID- 23113540
TI  - Efficacy of porcine placental extract on shoulder stiffness in climacteric women.
AB  - OBJECTIVES: Some of the most common climacteric symptoms are somatic symptoms,
      such as muscle and joint pain, which cause limitations in performing daily tasks.
      This study aimed to assess whether oral porcine placental extract (PPE) affects
      patients with shoulder stiffness, one of the most common types of muscle-tendon
      stiffness, in climacteric women and postmenopausal women with hormone therapy
      (HT). METHODS: Sixty-six climacteric women (33 each in the control and study
      groups) with shoulder stiffness and 54 postmenopausal women (27 each in the
      control and study groups) with HT-resistant shoulder stiffness were enrolled into
      this open-label, randomized, controlled study. The control subjects received Toki
      shakuyaku-san (TJ23; 7.5 g/day, daily per os), an oral herbal remedy used to
      alleviate climacteric symptoms, and study subjects received PPE orally for 24
      weeks in climacteric women and for 12 weeks in postmenopausal women with HT.
      Changes in the degree of shoulder stiffness were evaluated by the Visual Analog
      Scale (VAS). RESULTS: Treatment with PPE was significantly effective in reducing
      the VAS score for shoulder stiffness during the study period compared with the
      control group in both climacteric and postmenopausal women with HT. The VAS score
      at the end of treatment was significantly reduced (p < 0.01 vs. baseline) by
      76.4% for climacteric women and 64.8% for postmenopausal women with HT compared
      with baseline. CONCLUSIONS: PPE is useful as an oral supplement for shoulder
      stiffness in climacteric women without HT or in postmenopausal women with HT
      resistant, long-term shoulder stiffness.

PMID- 23113539
TI  - Endometrial histopathology, ovarian changes and bleeding patterns among users of
      long-acting progestin-only contraceptives in Egypt.
AB  - OBJECTIVE: To evaluate endometrial and ovarian effects, and bleeding patterns,
      among users of Depo-Provera((r)), Norplant((r)), and Implanon((r)). STUDY DESIGN:
      One-hundred and fifty women, who had been using one of these long-acting
      progestin-only contraceptives (LAPCs) for at least the previous six months, with
      fifty in each of the groups, were assessed. RESULTS: All results are mentioned in
      the following sequence: (1) Depo-Provera((r)), (2) Norplant((r)), and (3)
      Implanon((r)). Normal bleeding was reported by 0%, 52%, and 8%; amenorrhoea or
      infrequent bleeding by 68%, 24%, and 72%; and abnormal bleeding by 32%, 24%, and
      20%, respectively (p < 0.001). Histological evaluation revealed an atrophic
      endometrium in 84%, 32%, and 28%, respectively (p < 0.0001); a progestin effect
      in 16%, 28%, and 62%, respectively (p < 0.0001), and a proliferative pattern in
      0%, 40%, and 10%, respectively (p < 0.0001). Endometrial thickness was 3 +/- 0.41
      mm, 3.62 +/- 0.65 mm, and 5.2 +/- 0.84 mm, respectively (p < 0.0001). Follicular
      growth in the ovaries was observed at ultrasound in 12%, 40%, and 72%,
      respectively (p < 0.001). CONCLUSION: Bleeding patterns, endometrial thickness,
      ovarian activity, and endometrial histology among Egyptian users of LAPCs
      differed significantly depending on the nature of the contraceptive.

PMID- 23113541
TI  - Light-controllable cucurbit[7]uril-based molecular shuttle.
AB  - The design and construction of novel artificial molecular machines can be
      categorized as a currently important field of modern chemistry. In the present
      work, a novel photoresponsive [3]rotaxane containing two cucurbit[7]uril (CB[7])
      rings and a dumbbell component consisting of one trans-azobenzene unit along with
      two viologen units was developed. Each viologen group was encircled by a CB[7]
      ring with a rapid shuttling equilibration distribution extended to the trans
      azobenzene unit located in the middle of the dumbbell component. Upon the trans
      to-cis photoisomerization of the azobenzene unit under UV light irradiation, a
      shuttling restriction of the CB[7] rings along the dumbbell component was
      observed. The equilibration distribution of the macrocycles on the dumbbell
      component can be recovered by the cis-to-trans photoisomerization of the
      azobenzene unit under visible light irradiation. Such a controllable shuttling
      process was fully characterized by (1)H NMR spectroscopy and was easily indicated
      by fluorescent changes of the [3]rotaxane.

PMID- 23113543
TI  - Whole-body hyperthermia combined with hyperthermic intraperitoneal chemotherapy
      for the treatment of stage IV advanced gastric cancer.
AB  - BACKGROUND: Currently known as a metastatic disease, stage IV gastric cancer
      cannot be cured by surgery, but treatments are recommended to relieve symptoms
      such as pain and to prolong survival. METHODS: With better access to metastases
      and certain large or inoperable tumours, we applied two treatment sessions of
      combined therapy of whole-body hyperthermia and hyperthermic intraperitoneal
      chemo-perfusion in the treatment group, while patients in the control group were
      treated with oxaliplatin combined with 5-fluorouracil chemotherapy or Xeloda. We
      used the RECIST criteria for outcome evaluation. RESULTS: With the combined
      treatment, we found the complete and partial remission rate of patients to be
      61.5%, and the rate of stable disease was 19.2%. Symptoms such as pain and a
      large volume of ascites were alleviated, and the quality of life was
      correspondingly improved. In addition, the combined treatment had a significant
      therapeutic benefit against the primary tumour and the metastases to the lymph
      nodes and liver. Survival time was also significantly prolonged (the 1-year
      survival rate was 38.5% compared to the control group rate of 19%). CONCLUSIONS:
      These results suggest that whole-body hyperthermia combined with hyperthermic
      intraperitoneal chemotherapy is an effective treatment for patients with advanced
      gastric malignancies.

PMID- 23113544
TI  - Regulation of human RNase-L by the miR-29 family reveals a novel oncogenic role
      in chronic myelogenous leukemia.
AB  - The endoribonuclease RNase-L is the terminal component of an interferon-regulated
      RNA decay pathway known as the 2'-5'-oligoadenylate (2-5A) system, whose
      established functions include antimicrobial and tumor suppressive activities.
      RNase-L activity requires binding of the small molecule 2-5A, leading to RNase-L
      dimerization and cleavage of single-stranded RNA. RNase-L expression is
      controlled post-transcriptionally by its 3'-untranslated region (3' UTR), which
      exerts a strong negative effect on RNase-L levels. MicroRNAs (miRNAs) are a class
      of small noncoding RNAs that repress expression of target genes by binding to
      regions of complementarity often in the 3' UTR. The miR-29 family acts as a tumor
      suppressor in several cancers, including acute and chronic myelogenous leukemia
      (CML), and has many oncogenic targets. We report that the miR-29 family represses
      RNase-L protein expression across several cell types. Using a luciferase
      reporter, we showed that miR-29 acts via 4 target sites within the RNASEL 3' UTR.
      Mutation of all sites is required for abrogation of miR-29 repression. In light
      of the reported tumor suppressive role of miR-29 in K562 CML cells and miR-29
      repression of RNase-L in these cells, we generated K562 cells with stable RNase-L
      knockdown and demonstrated that loss of RNase-L inhibits proliferation in vitro
      as well as tumor growth in a xenograft model. Our findings identify a previously
      unknown miRNA regulator of RNase-L expression and support a novel oncogenic role
      for RNase-L in CML and potentially other hematopoietic malignancies.

PMID- 23113545
TI  - CeCl3.7H2O catalyzed C-C and C-N bond-forming cascade cyclization with subsequent
      side-chain functionalization and rearrangement: a domino approach to
      pentasubstituted pyrrole analogues.
AB  - CeCl(3).7H(2)O is found as an efficient catalyst for new intermolecular domino
      reactions of three-, four- and seven-component assemblies of common precursors
      under benign reaction conditions. Generation of enaminioesters from beta-keto
      esters and primary amines, activation of their allylic sp(3) C-H, vinylic sp(2) C
      H and N-H bonds, multi C-C and C-N bond-forming cascade cyclization with 1,2
      diketones and subsequent side-chain alkylation have been developed to construct
      functionalized pentasubstituted pyrroles and their chiral analogues. The scope of
      the domino reaction is successfully explored toward synthesis of highly aryl
      substituted pyrroles, pentasubstituted pyrroles bearing C2-olefinic side-chain
      and spiro-2-pyrrolinones and their chiral analogues via unusual side-chain
      amination, elimination and ring contraction. The new domino reaction is
      operationally simple, robust, substrate specific, selective and high yielding.

PMID- 23113546
TI  - Evidence that the biofungicide Serenade (Bacillus subtilis) suppresses clubroot
      on canola via antibiosis and induced host resistance.
AB  - This study investigated how the timing of application of the biofungicide
      Serenade (Bacillus subtilis QST713) or it components (product filtrate and
      bacterial cell suspension) influenced infection of canola by Plasmodiophora
      brassicae under controlled conditions. The biofungicide and its components were
      applied as a soil drench at 5% concentration (vol/vol or equivalent CFU) to a
      planting mix infested with P. brassicae at seeding or at transplanting 7 or 14
      days after seeding (DAS) to target primary and secondary zoospores of P.
      brassicae. Quantitative polymerase chain reaction (qPCR) was used to assess root
      colonization by B. subtilis as well as P. brassicae. The biofungicide was
      consistently more effective than the individual components in reducing infection
      by P. brassicae. Two applications were more effective than one, with the
      biofungicide suppressing infection completely and the individual components
      reducing clubroot severity by 62 to 83%. The biofungicide also reduced genomic
      DNA of P. brassicae in canola roots by 26 to 99% at 7 and 14 DAS, and the qPCR
      results were strongly correlated with root hair infection (%) assessed at the
      same time (r = 0.84 to 0.95). qPCR was also used to quantify the transcript
      activity of nine host-defense-related genes in inoculated plants treated with
      Serenade at 14 DAS for potential induced resistance. Genes encoding the jasmonic
      acid (BnOPR2), ethylene (BnACO), and phenylpropanoid (BnOPCL and BnCCR) pathways
      were upregulated by 2.2- to 23-fold in plants treated with the biofungicide
      relative to control plants. This induced defense response was translocated to the
      foliage (determined based on the inhibition of infection by Leptosphaeria
      maculans). It is possible that antibiosis and induced resistance are involved in
      clubroot suppression by Serenade. Activity against the infection from both
      primary and secondary zoospores of P. brassicae may be required for maximum
      efficacy against clubroot.

PMID- 23113547
TI  - Verticillium dahliae populations from mint and potato are genetically divergent
      with predominant haplotypes.
AB  - In total, 286 Verticillium dahliae isolates from mint, potato, and other hosts
      and substrates were characterized for mating type, vegetative compatibility group
      (VCG), and multilocus microsatellite haplotype to determine population genetic
      structure among populations infecting mint and potato. Populations from mint and
      potato fit a clonal reproductive model, with all isolates a single mating type
      (MAT1-2) and multiple occurrences of the same haplotypes. Haplotype H02
      represented 88% of mint isolates and was primarily VCG2B, while haplotype H04
      represented 70% of potato isolates and was primarily VCG4A. Haplotypes H02 and
      H04 typically caused severe disease on mint and potato, respectively, in
      greenhouse assays regardless of host origin. Principal coordinate analysis and
      analysis of molecular variance indicated that mint and potato populations were
      significantly genetically diverged (P = 0.02), and identification of private
      alleles and estimation of migration rates suggested restricted gene flow.
      Migration was detected between infected potato plants and seed tubers, infested
      tare soil, and field soils. Genetic differentiation of V. dahliae from mint and
      potato may be due to the occurrence of a single mating type and differences in
      VCG. Populations of V. dahliae in potato and mint were characterized by the
      presence of aggressive, clonally reproducing haplotypes which are widely
      distributed in commercial mint and potato production.

PMID- 23113548
TI  - Fine mapping of leaf rust resistance gene LrZH84 using expressed sequence tag and
      sequence-tagged site markers, and allelism with other genes on wheat chromosome
      1B.
AB  - Zhou 8425B, possessing the leaf rust resistance gene LrZH84, is an elite wheat
      (Triticum aestivum) parental line in the Yellow-Huai Valley region of China. In
      the present study, 2,086 F(2) plants derived from Zhou 8425B/Chinese Spring were
      used for fine mapping of LrZH84 with expressed sequence tag (EST) and sequence
      tagged site (STS) markers. Seventy inter-simple sequence repeat EST and STS
      markers on 1BL were used to screen the two parents and resistant and susceptible
      bulks; those polymorphic were used to analyze the entire F(2) population. Three
      EST markers (BF474863, BE497107, and CD373538) were closely linked to LrZH84,
      with genetic distances of 0.7, 0.7, and 1.7 cM, respectively. STS marker Hbsf-1
      was developed from the sequences of polymerase chain reaction fragments amplified
      from EST marker BF474863. LrZH84 was 8.19 cM proximal to Lr44, but may be allelic
      to LrXi and LrG98 although they showed different reactions with some Puccinia
      triticina pathotypes.

PMID- 23113549
TI  - A computational study of injury severity and pattern sustained by overweight
      drivers in frontal motor vehicle crashes.
AB  - The objective of this study was to examine the role of body mass and subcutaneous
      fat in injury severity and pattern sustained by overweight drivers. Finite
      element models were created to represent the geometry and properties of
      subcutaneous adipose tissue in the torso with data obtained from reconstructed
      magnetic resonance imaging data-sets. The torso adipose tissue models were then
      integrated into the standard multibody dummy models together with increased
      inertial parameters and sizes of the limbs to represent overweight occupants.
      Frontal crash simulations were carried out considering a variety of occupant
      restraint systems and regional body injuries were measured. The results revealed
      that differences in body mass and fat distribution have an impact on injury
      severity and pattern. Even though the torso adipose tissue of overweight subjects
      contributed to reduce abdominal injury, the momentum effect of a greater body
      mass of overweight subjects was more dominant over the cushion effect of the
      adipose tissue, increasing risk of other regional body injuries except abdomen.
      Through statistical analysis of the results, strong correlations (p < 0.01) were
      found between body mass index and regional body injuries except neck injury. The
      analysis also revealed that a greater momentum of overweight males leads to
      greater forward torso and pelvic excursions that account for higher risks (p <
      0.001) of head, thorax and lower extremity injury than observed in non-overweight
      males. The findings have important implications for improving the vehicle and
      occupant safety systems designed for the increasing global obese population. 

PMID- 23113552
TI  - Complex open-framework germanate built by 8-coordinated Ge(10) clusters.
AB  - A novel open-framework germanate |(C5H14N2)2(C5H12N2)0.5(H2O)2.5|[Ge12.5O26(OH)2]
      with three-dimensional 10- and 11-ring channels, denoted as SU-67, has been
      synthesized under hydrothermal conditions using 2-methylpiperazine (MPP) as the
      structure-directing agent (SDA). The synthesis is intimately related to that of
      JLG-5, a tubular germanate built from Ge7 clusters. The influences of synthesis
      parameters are discussed. A strong influence of the hydrofluoric acid quantity on
      the resulting cluster building units can be concluded. The framework of SU-67 is
      based on an elaborate topological pattern of connected Ge10 clusters forming
      intersecting 10- and 11-ring channels and has a low framework density (12.4 Ge
      atoms per 1000 A(3)). We have discovered that the topology of SU-67 is a new 8
      connected nce-8-I41/acd net. Strong hydrogen bonding among the organic SDAs,
      water molecules, and Ge10 clusters resulted in helical networks in SU-67. 

PMID- 23113551
TI  - Cost effectiveness of guanfacine extended-release versus atomoxetine for the
      treatment of attention-deficit/hyperactivity disorder: application of a matching
      adjusted indirect comparison.
AB  - BACKGROUND: About 7% of children and adolescents are diagnosed with attention
      deficit/hyperactivity disorder (ADHD) in the US. Patients with ADHD who are
      intolerant of or do not have an optimal response to stimulants often use non
      stimulants as alternative therapies. Guanfacine extended-release (GXR) and
      atomoxetine (ATX) are the only non-stimulants approved by the US Food and Drug
      Administration for once-daily use in the treatment of children and adolescents
      with ADHD in the US. ATX has been on the market since 2002 while GXR was recently
      approved in 2009. To date, there is no comparative effectiveness or cost
      effectiveness study comparing the two drugs. OBJECTIVES: The aim of this study
      was to assess the cost effectiveness of GXR versus ATX for the treatment of ADHD
      in children and adolescents, using the comparative efficacy results from a
      matching-adjusted indirect comparison (MAIC). METHODS: The MAIC method was used
      to compare the efficacy between GXR (target dose and lower doses) and ATX (target
      dose) in the absence of head-to-head clinical trials. Individual patients in the
      GXR trials were weighted such that the summary baseline characteristics and the
      efficacy of the placebo arm of the GXR trials matched exactly with those from
      published ATX trials. After weighting, the efficacy (i.e. change in the ADHD
      rating scale, fourth edition [ADHD-RS-IV] total score from baseline) was compared
      between each GXR dosing group and the ATX group. The results from the MAIC
      analyses were used to populate a 1-year Markov model that is used to compare the
      cost effectiveness of GXR versus ATX from a US third-party payer perspective.
      Effectiveness outcomes for each treatment group were estimated as the proportion
      of responders, defined as patients with >=25% reduction in ADHD-RS-IV total score
      from baseline, and average quality-adjusted life years (QALYs). Utilities
      associated with response/non-response and disutilities due to adverse events were
      applied in the model. Costs included drug and medical service costs and were
      inflated to 2011 US dollars ($US). Incremental cost/QALY and incremental
      cost/responder were estimated. Univariate sensitivity analyses were conducted by
      varying all model parameters, including costs, utilities, and response rate.
      RESULTS: The target dose of GXR was 0.12 mg/kg/day. In match-adjusted populations
      with balanced baseline characteristics, patients receiving GXR at the dose of
      0.09-0.12(p = 0.0016) [DOSAGE ERROR CORRECTED] and 0.075-0.09 mg/kg/day (p =
      0.0248) had better efficacy, while those receiving GXR at the dose of 0.046-0.075
      mg/kg/day had comparable efficacy (p = 0.0699), compared with patients receiving
      ATX at the target dose of 1.2 mg/kg/day. In the base case of the cost
      effectiveness analysis (CEA), GXR had incremental cost-effectiveness ratios of
      $US10 637/QALY and $US853/responder, compared with ATX (incremental costs: $US74;
      incremental effectiveness: 0.007 QALYs and 86 responders per 1000 patients
      treated). Results of all univariate sensitivity analyses showed that the model
      results were robust to changes in model inputs. CONCLUSIONS: To our knowledge,
      this is the first application of the novel comparative efficacy method of MAIC to
      a CEA model. The MAIC results indicate that GXR (0.075-0.12 mg/kg/day) was more
      effective than ATX (1.2 mg/kg/day) in the trial population. The CEA results
      indicate that GXR is cost effective compared with ATX for the treatment of ADHD
      in children and adolescents.

PMID- 23113553
TI  - Comparison of smear microscopy, culture, and real-time PCR for quantitative
      detection of Mycobacterium tuberculosis in clinical respiratory specimens.
AB  - BACKGROUND: As a rapid diagnostic technique, the real-time polymerase chain
      reaction (PCR) can detect Mycobacterium tuberculosis with a high sensitivity and
      specificity. However, further studies are needed to confirm it as a standard
      method. In this study, we evaluated the cyp141 gene for the detection and
      quantification of M. tuberculosis in respiratory specimens and compared the
      results with direct microscopy and culture. METHODS: Sputum samples (n = 247)
      were collected from patients of the different provinces of Iran. DNA was
      extracted from clinical specimens and H37Rv strain. After measuring the standard
      strain DNA concentration by NanoDrop and using the Avogadro number, the DNA was
      diluted 6 times in order to obtain 1 * 10(6) to 10 template copies. A Taqman
      probe was designed for detection of the target in a real-time PCR using the
      specific primers. RESULTS: Of 247 samples, 135 (55%) were culture-negative. Of
      112 (45%) culture-positive samples, 88 were positive by both smear and culture
      and 24 were smear-negative but culture-positive. The real-time PCR enumerated
      1.5E + 02 to 4.3E+ 03, 8.5E + 03 to 5.5E + 04, 7.2E + 04 to 1.1E + 06, and 1.2E +
      06 to 8.1E + 07 M. tuberculosis cells in the specimens with smear-negative, 1
      plus, 2-plus, and 3-plus codes, respectively. The overall sensitivity,
      specificity, positive predictive value (PPV), and negative predictive value (NPV)
      of the real-time PCR were 90.2% (101/112), 97.8% (132/135), 97.1%, and 92.3%,
      respectively. CONCLUSIONS: The overall sensitivity and specificity, the results
      in comparison with those of the Xpert MTB/RIF kit, and the good correlation with
      molecular and phenotypic methods, show that cyp141 could be a good target for the
      quantification of M. tuberculosis in sputum and possibly other clinical
      specimens.

PMID- 23113554
TI  - Human cytochrome b5 reductase: structure, function, and potential applications.
AB  - Cytochrome b5 reductase is a flavoprotein that is produced as two different
      isoforms that have different localizations. The amphipathic microsomal isoform,
      found in all cell types with the exception of erythrocytes, consists of one
      hydrophobic membrane-anchoring domain and a larger hydrophilic flavin catalytic
      domain. The soluble cytochrome b5 reductase isoform, found in human erythrocytes,
      is a truncated protein that is encoded by an alternative transcript and consists
      of the larger domain only. Cytochrome b5 reductase is involved in the transfer of
      reducing equivalents from the physiological electron donor, NADH, via an FAD
      domain to the small molecules of cytochrome b5. This protein has received much
      attention from researchers due to its involvement in many oxidation and reduction
      reactions, such as the reduction of methemoglobin to hemoglobin. Autosomal
      cytochrome b5 reductase gene deficiency manifests with the accumulation of
      oxidized Fe+3 and recessive congenital methemoglobinemia in humans. In this
      article, we provide a comprehensive overview of the structure and function of
      cytochrome b5 reductase from different eukaryotic sources and its potential use
      in the food industry, biosensor, and diagnostic areas.

PMID- 23113555
TI  - The effects of dynamic stretching on the passive properties of the muscle-tendon
      unit.
AB  - The purpose of this study was to examine the effects of dynamic stretching on the
      passive biomechanical properties and isometric muscle strength of the knee
      flexors. Fourteen healthy men (mean +/- s: age = 24 +/- 3 years) performed
      passive range of motion assessments and isometric maximal voluntary contractions
      of the knee flexors at knee joint angles of 35 degrees , 50 degrees , 65 degrees
      , 80 degrees , and 95 degrees  below full knee extension before and after dynamic
      stretching. In addition, electromyographic amplitude was recorded from the biceps
      femoris during the maximal voluntary contractions. Passive stiffness and passive
      resistive torque were measured during pre- and post-dynamic stretching. The
      dynamic stretching included the participant extending their right leg outwards to
      the end range motion and pulling their leg back towards the body while seated in
      the isokinetic dynamometer for four 30-s bouts with 20-s rest between bouts.
      Passive range of motion increased while passive stiffness and passive resistive
      torque decreased following dynamic stretching. Peak torque decreased at knee
      joint angles of 65 degrees  and 80 degrees  below full extension, while
      electromyographic amplitude decreased following dynamic stretching. Dynamic
      stretching resulted in changes to passive stiffness and passive resistive torque
      that are typically reported following static stretching, however, there were
      decreases in peak torque at two of the knee joint angles.

PMID- 23113556
TI  - Discovery of novel human aquaporin-1 blockers.
AB  - Human aquaporin-1 (hAQP1) is a water channel found in many tissues and
      potentially involved in several human pathologies. Selective inhibitors of hAQP1
      are discussed as novel treatment opportunities for glaucoma, brain edema,
      inflammatory pain, and certain types of cancer. However, only very few potent and
      chemically attractive blockers have been reported to date. In this study we
      present three novel hAQP1 blockers that have been identified by virtual screening
      and inhibit water flux through hAQP1 in Xenopus laevis oocyte swelling assays at
      low micromolar concentrations. The newly discovered compounds display no chemical
      similarity to hitherto known hAQP1 blockers and bind at the extracellular
      entrance of the channel, close to the ar/R selectivity filter. Furthermore,
      mutagenesis studies showed that Lys36, which is not conserved among the hAQP
      family, is crucially involved in binding and renders the discovered compounds
      suitable as leads for the development of selective hAQP1 inhibitors.

PMID- 23113557
TI  - Direct catalytic anti-markovnikov hydroetherification of alkenols.
AB  - A direct intramolecular anti-Markovnikov hydroetherification reaction of alkenols
      is described. By employing catalytic quantities of commercially available 9
      mesityl-10-methylacridinium perchlorate and 2-phenylmalononitrile as a redox
      cycling source of a H-atom, we report the anti-Markovnikov hydroetherification of
      alkenes with complete regioselectivity. In addition, we present results
      demonstrating that this novel catalytic system can be applied to the anti
      Markovnikov hydrolactonization of alkenoic acids.

PMID- 23113560
TI  - Risk of self-reported Chlamydia trachomatis infection by social and lifestyle
      factors: a study based on survey data from young adults in Stockholm, Sweden.
AB  - OBJECTIVE: To analyse the associations between demographic, socio-economic and
      lifestyle factors, and the risk of self-reported chlamydial infection among young
      adults (20-29 years old) in Stockholm, Sweden. METHODS: This study was based on
      the Stockholm Public Health Survey of 2006 (N = 4278). Demographic factors
      (gender, age, and country of birth), socio-economic factors (individual and
      parental educational levels, individual income level, and employment status), and
      lifestyle factors (body mass index, mental health, alcohol consumption, and
      partnership status) were taken into account. Possible associations were analysed
      by logistic regression. RESULTS: The risk of self-reported chlamydial infection
      decreases with age, is higher among individuals both who personally, and whose
      parents, were educated to high school level compared to university level
      education, and is higher among those employed, unemployed or on sick-leave/pre
      retired compared to students. The risk of chlamydial infection is also higher
      among subjects who report greater alcohol consumption, and those who live without
      a partner. After considering demographic, socio-economic and lifestyle factors,
      the associations with age, educational level, employment status and alcohol
      consumption are strong and statistically significant. CONCLUSION: Indicators of
      risk-taking behaviours, especially in settings with generally little educational
      ambition or options, should be incorporated in the design of STI prevention
      strategies.

PMID- 23113558
TI  - In-vitro replication studies on O(2)-methylthymidine and O(4)-methylthymidine.
AB  - O(2)- and O(4)-methylthymidine (O(2)-MdT and O(4)-MdT) can be induced in tissues
      of laboratory animals exposed with N-methyl-N-nitrosourea, a known carcinogen.
      These two O-methylated DNA adducts have been shown to be poorly repaired and may
      contribute to the mutations arising from exposure to DNA methylating agents.
      Here, in vitro replication studies with duplex DNA substrates containing site
      specifically incorporated O(2)-MdT and O(4)-MdT showed that both lesions blocked
      DNA synthesis mediated by three different DNA polymerases, including the
      exonuclease-free Klenow fragment of Escherichia coli DNA polymerase I (Kf(-)),
      human DNA polymerase kappa (pol kappa), and Saccharomyces cerevisiae DNA
      polymerase eta (pol eta). Results from steady-state kinetic measurements and LC
      MS/MS analysis of primer extension products revealed that Kf(-) and pol eta
      preferentially incorporated the correct nucleotide (dAMP) opposite O(2)-MdT,
      while O(4)-MdT primarily directed dGMP misincorporation. While steady-state
      kinetic experiments showed that pol kappa-mediated nucleotide insertion opposite
      O(2)-MdT and O(4)-MdT is highly promiscuous, LC-MS/MS analysis of primer
      extension products demonstrated that pol kappa favorably incorporated the
      incorrect dGMP opposite both lesions. Our results underscored the limitation of
      the steady-state kinetic assay in determining how DNA lesions compromise DNA
      replication in vitro. In addition, the results from our study revealed that, if
      left unrepaired, O-methylated thymidine lesions may constitute important sources
      of nucleobase substitutions emanating from exposure to alkylating agents.

PMID- 23113561
TI  - Racial disparities in outcomes after spinal cord injury.
AB  - Spinal Cord Injury (SCI) is an acute trauma to the neural elements resulting in
      temporary or permanent sensory and motor deficit. Studies have indicated that
      although 66% of SCI occur in Caucasians, there are a growing number of other
      racial groups affected by SCI. Furthermore, there has been a lack of research
      concerning racial disparities in outcomes following SCI. As such, a retrospective
      analysis using the National Trauma Data Bank (NTDB) from 2000 to 2009 was
      performed. African Americans, Caucasians, Hispanics, Asians, and Native Americans
      were included in the study. We calculated adjusted odds ratios (OR) to examine
      the relationship between racial backgrounds and mortality, length of intensive
      care unit (ICU) stay, length of hospital stay, in-hospital complications, and
      patient disposition. Our results showed that significant differences were found
      in length of hospital stay, with African American and Hispanic populations having
      longer hospital stays than Caucasian and Asians. For all type complications,
      African Americans (OR 1.228, confidence interval [CI] 1.11-1.356) and Native
      Americans (OR 1.618, CI 1.083-2.419) were more likely than Caucasian and Hispanic
      patients to have in-hospital complications. For disposition status, African
      Americans (OR 0.844, CI 0.730-0.976) and Asians (OR 0.475, CI 0.297-0.760) were
      much less likely than Caucasians or Hispanic populations to be discharged to an
      acute rehabilitation program. The results from this large-scale study (n=18,671)
      demonstrate a number of racial disparities following SCI at the national level,
      including rate of complications, length of stay, and disposition to acute
      rehabilitation centers. This should raise awareness to cultural differences but
      also serve as an opportunity to reduce gaps in care across ethnicities for this
      universally life-altering condition.

PMID- 23113562
TI  - Effectiveness of an integrative health-care model for climacteric-stage women.
AB  - OBJECTIVES: To evaluate an integrative health-care model (IHCM) with an
      empowerment approach for self-care in terms of improving health-related quality
      of life (HR-QoL) and lifestyle. METHODS: We conducted a field trial with one
      intervention (IHCM) and one comparison group receiving usual care (UC), with ex
      ante and ex post measurements. The IHCM was provided for 3 months to each woman
      in the first group, with follow-up of both groups at 3 and 6 months. The
      differences in differences estimator was used to assess the effect of
      intervention, adjusting for clinically important covariates in the framework of a
      generalized linear regression model. RESULTS: A total of 380 women (IHCM 190 and
      UC 190) participated in the study. The differences in differences estimator
      between IHCM and UC for aerobic physical activity was 81 and 87 min/week at 3 and
      6 months, respectively; for consumption of dairy products, fruit and vegetables
      the estimator was 4.8, 6.6 and 9.4 servings per week respectively at 3 months,
      and 3.9, 6.3 and 9.7 servings at 6 months. The effect of IHCM on HR-QoL at 3
      months was greater for the domains of vasomotor, somatic symptoms and sleep
      problems (11.7, 10.0 and 13.2 points, respectively); at 6 months the differences
      of major positive change were observed in the domains of memory/concentration,
      vasomotor symptoms and sleep problems (12.2, 10.4 and 10.8 points, respectively).
      CONCLUSION: The results support the importance of patient-centered health care
      during the climacteric stage, within integrative care programs with an
      empowerment approach.

PMID- 23113563
TI  - Design and synthesis of a photoaromatization-based two-stage photobase generator
      for pitch division lithography.
AB  - The synthesis of a two-stage photobase generator (PBG) based on photoinduced
      aromatization is described. This material was designed for use in resolution
      enhanced photolithography. Computer modeling predicts that a delay in the onset
      of base generation can lead to improved image quality. This delay can be realized
      by a PBG that must undergo two sequential photoreactions for each molecule of
      base generated. Toward that end, latent PBGs were designed that are oxime esters
      of aliphatic acids, which undergo Norrish type II reactions to yield oxime esters
      of aromatic acids that are efficient PBGs.

PMID- 23113564
TI  - Age-related changes in skin barrier function - quantitative evaluation of 150
      female subjects.
AB  - The protection against water loss and the prevention of substances and bacteria
      penetrating into the body rank as the most important functions of the skin. This
      so-called 'skin barrier function' is the natural frontier between the inner
      organism and the environment, and is primarily formed by the epidermis. An
      impairment of the skin barrier function is often found in diseased and damaged
      skin. An influence of ageing on skin barrier function is widely accepted, but has
      not been conclusively evaluated yet. Therefore, the aim of this clinical study
      was to assess the potential influence of ageing on skin barrier function,
      including transepidermal water loss (TEWL), stratum corneum hydration, sebum
      content and pH value. One hundred and fifty healthy women aged 18-80, divided
      into five age groups with 30 subjects each, were evaluated in this study. TEWL,
      hydration level, sebum secretion and pH value of hydro-lipid acid film were
      measured with worldwide acknowledged biophysical measuring methods at cheek,
      neck, decollete, volar forearm and dorsum of hand. Whereas TEWL and stratum
      corneum hydration showed only very low correlation with subject's age, the sebum
      production decreased significantly with age, resulting in the lowest skin surface
      lipids levels measured in subjects older than 70 years. The highest skin surface
      pH was measured in subjects between 50 and 60 years, whereas the eldest age group
      had the lowest mean pH. The dorsum of the hand was the location with the highest
      TEWL and lowest stratum corneum hydration in all age groups. The results show
      that only some parameters related to skin barrier function are influenced by
      ageing. Whereas sebum production decreases significantly over lifetime and skin
      surface pH is significantly increased in menopausal woman, TEWL and stratum
      corneum hydration show only minor variations with ageing.

PMID- 23113565
TI  - Amelanotic melanoma mimicking keratoacanthoma: the diagnostic role of dermoscopy.

PMID- 23113566
TI  - CT-based semi-automatic quantification of vertebral fracture restoration.
AB  - Minimally invasive surgeries aiming to restore fractured vertebral body are
      increasing; therefore, our goals were to create a 3D vertebra reconstruction
      process and design clinical indices to assess the vertebral restoration in terms
      of heights, angles and volumes. Based on computed tomography (CT)-scan of the
      vertebral spine, a 3D reconstruction method as well as relevant clinical indices
      were developed. First, a vertebra initial solution requiring 5 min of manual
      adjustments is built. Then an image processing algorithm places this solution in
      the CT-scan images volume to adjust the model's nodes. On the vertebral body's
      anterior and posterior parts, nine robust heights, volume and endplate angle
      measurement methods were developed. These parameters were evaluated by
      reproducibility and accuracy studies. The vertebral body reconstruction accuracy
      was 1.0 mm; heights and volume accuracy were, respectively, 1.2 and 179 mm3. In
      conclusion, a 3D vertebra reconstruction process requiring little user time was
      proposed as well as 3D clinical indices assessing fractured and restored
      vertebra.

PMID- 23113567
TI  - Treatment of soft tissue recessions at titanium implants using a resorbable
      collagen matrix: a pilot study.
AB  - OBJECTIVES: To histologically assess the effectiveness of a porcine-derived
      collagen matrix (CM) and a subepithelial connective tissue graft (CTG) for the
      coverage of single mucosal recessions at osseointegrated dental implants.
      MATERIALS AND METHODS: Chronic-type mucosal Miller Class I-like recessions (mean
      clinical defect height: 0.67 +/- 0.33-1.16 +/- 0.19 mm) were established at the
      buccal aspect of titanium implants with platform switch in six beagle dogs. The
      defects were randomly allocated to either (1) coronally advanced flap surgery
      (CAF) + CM, (2) CAF + CTG or (3) CAF alone. At 12 weeks, histomorphometrical
      measurements were made (e.g.) between the implant shoulder (IS) and the mucosal
      margin (PM) and IS and the outer contour of the adjacent soft tissue (mucosal
      thickness [MT]). RESULTS: All treatment procedures investigated were associated
      with an almost complete soft tissue coverage of the defect area (i.e. coronal
      positioning of PM relative to IS). Mean IS-PM and MT values tended to be
      increased in both CAF + CM (1.04 +/- 0.74 mm/0.71 +/- 0.55 mm) and CAF + CTG
      (0.88 +/- 1.23 mm/0.62 +/- 0.66 mm) groups when compared with CAF (0.16 +/- 0.28
      mm/0.34 +/- 0.23 mm) alone. These differences, however, did not reach statistical
      significance. CONCLUSIONS: Within the limits of this pilot study, it was
      concluded that all treatment procedures investigated were effective in covering
      soft tissue recessions at titanium implants.

PMID- 23113568
TI  - Structural transformation of isopropylamine semiclathrate hydrates in the
      presence of methane as a coguest.
AB  - Guest-induced structural transformation in amine semiclathrate hydrates is a
      unique pattern caused by modifying the hydrophobic-hydrophilic balance, and thus,
      it can be applied to potential gas storage and transportation areas. The
      experimental results of the structural transformation of isopropylamine (IPA)
      semiclathrate hydrates in the presence of methane (CH(4)) as a coguest are
      presented with a focus on the macroscopic phase behavior and microscopic
      analytical methods such as powder X-ray diffraction (PXRD) and NMR spectroscopy.
      The introduction of CH(4) molecules as coguests changed the structure of the
      IPA.8.0H(2)O semiclathrate hydrates (hexagonal, P6(3)/mmc) to sII gas hydrates
      (cubic, Fd3m). The microscopic analysis results indicate that the guest gas
      distribution and the clathrate hydrate composition can be altered with adjustment
      of the IPA concentration. The overall experimental results are valuable for
      increased understanding of the stability conditions, structural details, and
      guest-host interactions in hydrophobic guest gas + IPA clathrate hydrates.

PMID- 23113569
TI  - New insights into the electronic structure and reactivity of one-electron
      oxidized copper(II)-(disalicylidene)diamine complexes.
AB  - The neutral and one-electron oxidized Cu(II) six-membered chelate 1,3-Salcn (1,3
      Salcn = N,N'-bis(3,5-di-tert-butylsalicylidene)-1,3-cyclohexanediamine) complexes
      have been investigated and compared with the five-membered chelate 1,2-Salcn
      (N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexane-(1R,2R)-diamine)
      complexes. Cyclic voltammetry of Cu(1,3-Salcn) showed two reversible redox waves
      at 0.48 and 0.68 V, which are only 0.03 V higher than those of Cu(1,2-Salcn).
      Reaction of Cu(1,3-Salcn) with 1 equiv of AgSbF6 afforded the oxidized complex
      which exists as a ligand-based radical species in solution and in the solid
      state. The X-ray crystal structure of the oxidized complex, [Cu(1,3-Salcn)]SbF6,
      exhibited an asymmetric metal binding environment with a longer Cu-O bond and
      quinoid distortion in the phenolate moiety on one side, demonstrating at least
      partial ligand radical localization in the solid state. The ligand oxidation is
      also supported by XPS and temperature dependent magnetic susceptibility. The
      electronic structure of the [Cu(1,3-Salcn)](+) complex was further probed by UV
      vis-NIR, resonance Raman, and electron paramagnetic resonance (EPR) measurements,
      and by theoretical calculations, indicating that the phenoxyl radical electron is
      relatively localized on one phenolate moiety in the molecule. The reactivity of
      [Cu(1,3-Salcn)](+) with benzyl alcohol was also studied. Quantitative conversion
      of benzyl alcohol to benzaldehyde was observed, with a faster reaction rate in
      comparison with [Cu(1,2-Salcn)](+). The kinetic isotope effect (KIE = k(H)/k(D))
      of benzyl alcohol oxidation by [Cu(1,3-Salcn)](+) was estimated to be 13, which
      is smaller than the value reported for [Cu(1,2-Salcn)](+). The activation energy
      difference between [Cu(1,2-Salcn)](+) and [Cu(1,3-Salcn)](+) was in good
      agreement with the energy calculated from KIE. This correlation suggests that the
      Cu(II)-phenoxyl radical species, characterized for [Cu(1,2-salcn)](+) is more
      reactive for hydrogen abstraction from benzyl alcohol in comparison to the 1:1
      mixture of Cu(III)-phenolate and Cu(II)-phenoxyl radical species, [Cu(1,2
      Salcn)](+). Thus, the Cu(II)-phenoxyl radical species accelerates benzyl alcohol
      oxidation in comparison with the Cu(III)-phenolate ground state complex, in spite
      of the similar activated intermediate and oxidation pathway. 

PMID- 23113571
TI  - Strain-promoted "click" modification of a mesoporous metal-organic framework.
AB  - Strain-promoted "click" chemistry is used to post-synthetically modify the pore
      walls of azide-functionalized mesoporous bio-MOF-100 (N(3)-bio-MOF-100). The
      reactions proceed in high yield and produce no byproduct. This new method was
      used to introduce various functional groups into the MOF mesopores, including
      succinimidyl ester bioconjugation moieties that allow for straightforward
      coupling of biomolecules to the pore walls.

PMID- 23113572
TI  - Can palliative care integrated within HIV outpatient settings improve pain and
      symptom control in a low-income country? A prospective, longitudinal, controlled
      intervention evaluation.
AB  - A high burden of pain, symptoms and other multidimensional problems persist
      alongside HIV treatment. WHO policy indicates palliative care as essential
      throughout the disease course. This study aimed to determine whether palliative
      care delivered from within an existing HIV outpatient setting improves control of
      pain and symptoms compared to standard care. A prospective, longitudinal
      controlled design compared patient outcomes at an outpatient facility that
      introduced palliative care training to clinicians and stocked essential
      palliative care drugs, to outcomes of a cohort of patients at a similar HIV care
      facility with no palliative care, in Tanzania. Inclusion criteria were clinically
      significant pain or symptoms. Patients were followed from baseline fortnightly
      until week 10 using validated self-report outcome measures. For the primary pain
      outcome, the required sample size of 120 patients was recruited. Odds of
      reporting pain reduced significantly more at intervention site (OR=0.60, 95% CI
      0.50-0.72) than at control (OR=0.85, 95% CI 0.80-0.90), p=0.001. For secondary
      outcomes, longitudinal analysis revealed significant difference in slope between
      intervention and control, respectively: Medical Outcomes Study-HIV (MOS-HIV)
      physical score 1.46 vs. 0.54, p=0.002; MOS-HIV mental health 1.13 vs. 0.26,
      p=0.006; and POS total score 0.84 vs. 0.18, p=0.001. Neither baseline CD4 nor
      antiretroviral therapy (ART) use was associated with outcome scores. These data
      are the first to report outcomes evaluating integrated HIV outpatient palliative
      care in the presence of ART. The data offer substantive evidence to underpin the
      existing WHO clinical guidance that states an essential role for palliative care
      alongside HIV treatment, regardless of prognosis.

PMID- 23113573
TI  - Language use depending on news frame and immigrant origin.
AB  - The purpose of this study was to analyze the effect of the media on individuals'
      specific language use in relation to a news story on immigration: the influence
      of the news frame and group cue. Abstraction, complexity of language use, and
      negative affective language were evaluated. The 523 participants were randomly
      distributed to each of the four experimental conditions: news frame (crime versus
      economic contribution) by group cue (geographical origin of the immigrants
      involved: Moroccans versus Latin Americans). Through content analysis of the
      ideas and reflections that arose after the participants read the different news
      stories, using the Linguistic Category Model (LCM; Semin & Fiedler, 1991) to
      measure abstract language and the Linguistic Inquiry and Word Count (LIWC;
      Pennebaker, Booth, & Francis, 2007) to analyze complex language and negative
      affective language, it emerged that abstract language and negative affective
      language were more frequent in the participants assigned to the news frame on
      crime. Complex language was more commonly used when the news frame referred to
      the economic contribution of immigrants. Regression analyses showed the mediating
      role of attitude to immigration in the effects of news frame on negative
      affective language. The bootstrap method was used to assess the magnitude of the
      indirect effect. A significant mediator effect was also found through structural
      equation modeling. Analyses of covariance showed one interaction between news
      frame and group cue: Among those who read the news story in a frame linking
      immigration to crime and Moroccan origin, abstract language was more
      characteristic. The results are discussed from the theoretical perspective of
      framing. 

PMID- 23113570
TI  - Anti-tumour strategies aiming to target tumour-associated macrophages.
AB  - Tumour-associated macrophages (TAMs) represent a predominant population of
      inflammatory cells that present in solid tumours. TAMs are mostly characterized
      as alternatively activated M2-like macrophages and are known to orchestrate
      nearly all stages of tumour progression. Experimental investigations indicate
      that TAMs contribute to drug-resistance and radio-protective effects, and
      clinical evidence shows that an elevated number of TAMs and their M2 profile are
      correlated with therapy failure and poor prognosis in cancer patients. Recently,
      many studies on TAM-targeted strategies have made significant progress and some
      pilot works have achieved encouraging results. Among these, connections between
      some anti-tumour drugs and their influence on TAMs have been suggested. In this
      review, we will summarize recent advances in TAM-targeted strategies for tumour
      therapy. Based on the proposed mechanisms, those strategies are grouped into four
      categories: (i) inhibiting macrophage recruitment; (ii) suppressing TAM survival;
      (iii) enhancing M1-like tumoricidal activity of TAMs; (iv) blocking M2-like
      tumour-promoting activity of TAMs. It is desired that further attention be drawn
      to this research field and more effort be made to promote TAM-targeted tumour
      therapy.

PMID- 23113574
TI  - Emotions, cognitive interference, and concentration disruption in youth sport.
AB  - We explored the relationship between emotions, cognitive interference,
      concentration disruption and performance in youth sport. In study 1, 150 youth
      sport athletes (Mage = 13.13 years, s = 1.79) completed measures of emotion,
      cognitive interference, and concentration disruption for their most recently
      completed competition. In Study 2, 46 female rhythmic gymnasts (Mage = 10.30
      years, s = 1.74) completed measures of emotion immediately before competition,
      and measures of cognitive interference and concentration disruption immediately
      after competition. Study 1 showed that anxiety and dejection were associated with
      more interfering thoughts and greater disruptions in concentration, whereas the
      effects of anger and happiness on interfering thoughts differed relative to the
      age of participants. Specifically, anger was associated with more interfering
      thoughts only in younger athletes and happiness was associated with fewer
      interfering thoughts only in older athletes. Study 2 showed that emotions
      experienced before competition were not strongly associated with cognitive
      interference or concentration disruption, but athletes reporting more thoughts of
      escape in competition were less successful in the competition as measured by
      objective performance scores. These findings demonstrate that emotions are
      important for cognitive interference and concentration disruption, and provide
      some initial evidence that cognitive interference is important for performance in
      youth sport.

PMID- 23113575
TI  - Synthesis of zinc-based nanomaterials: a biological perspective.
AB  - Nanoparticles are the materials characterised by dimensions of the order of 100
      nm or less. They exhibit a high surface/volume ratio leading to different
      properties very different from those of the bulk materials. The development of
      uniform nanoparticles has been intensively pursued because of their technological
      and fundamental scientific importance. A number of chemical methods are available
      and are extensively used, but these are often energy intensive and use toxic
      chemicals. An alternative approach for the synthesis of uniform nanoparticles is
      the biological route that occurs at ambient temperature, pressure and at neutral
      pH. The main aim of this review is to enlist and compare various methods of
      synthesis of zinc-based nanoparticles with emphasis on the biological method.

PMID- 23113576
TI  - Double shroud delivery of silica precursor for reducing hexavalent chromium in
      welding fume.
AB  - The welding process yields a high concentration of nanoparticles loaded with
      hexavalent chromium (Cr(6+)), a known human carcinogen. Previous studies have
      demonstrated that using tetramethylsilane (TMS) as a shielding gas additive can
      significantly reduce the Cr(6+) concentration in welding fume particles. In this
      study, a novel insulated double shroud torch (IDST) was developed to further
      improve the reduction of airborne Cr(6+) concentration by separating the flows of
      the primary shielding gas and the TMS carrier gas. Welding fumes were collected
      from a welding chamber in the laboratory and from a fixed location near the
      welding arc in a welding facility. The Cr(6+) content was analyzed with ion
      chromatography and X-ray photoelectron spectroscopy (XPS). Results from the
      chamber sampling demonstrated that the addition of 3.2 ~ 5.1% of TMS carrier gas
      to the primary shielding gas resulted in more than a 90% reduction of airborne
      Cr(6+) under all shielding gas flow rates. The XPS result confirmed complete
      elimination of Cr(6+) inside the amorphous silica shell. Adding 100 ~ 1000 ppm of
      nitric oxide or carbon monoxide to the shielding gas could also reduce Cr(6+)
      concentrations up to 57% and 35%, respectively; however, these reducing agents
      created potential hazards from the release of unreacted agents. Results of the
      field test showed that the addition of 1.6% of TMS carrier gas to the primary
      shielding gas reduced Cr(6+) concentration to the limitation of detection (1.1
      MUg/m(3)). In a worst-case scenario, if TMS vapor leaked into the environment
      without decomposition and ventilation, the estimated TMS concentration in the
      condition of field sampling would be a maximum 5.7 ppm, still well below its
      flammability limit (1%). Based on a previously developed cost model, the use of
      TMS increases the general cost by 3.8%. No visual deterioration of weld quality
      caused by TMS was found, although further mechanical testing is necessary.

PMID- 23113577
TI  - Bevacizumab in colorectal cancer: current and future directions.
AB  - Bevacizumab is a humanized monoclonal antibody to VEGF-A, an important
      therapeutic target through its proangiogenic effects on a variety of tumors.
      Bevacizumab has demonstrated clinically meaningful benefit in conjunction with
      chemotherapy for patients with metastatic colorectal cancer as well as other
      tumor types. Bevacizumab is a well-tolerated therapy with regard to toxicity, in
      keeping with its biological vascular effect. In this era of personalized
      medicine, current Phase II and III trials are further defining its role at
      various stages of metastatic disease and the optimal sequencing with cytotoxic
      and other targeted agents to achieve further improvements in patient outcome.
      Translational research for biomarker discovery and validation and further study
      into mechanisms of resistance are essential for future development and sustained
      benefit with this class of therapeutic agents.

PMID- 23113578
TI  - Sudden hearing loss in a patient receiving piperacillin/tazobactam and daptomycin
      for diabetic foot infection.

PMID- 23113579
TI  - Nontargeted analysis of DNA adducts by mass-tag MS: reaction of p-benzoquinone
      with DNA.
AB  - Using a method in which DNA adducts are discovered based on their conversion in a
      nucleotide form to phosphorimidazolides with isotopologue benzoylhistamines (or p
      bromobenzoylhistamine) prior to detection by MALDI-TOF-MS, we have profiled the
      adducts that form when calf thymus DNA is reacted in vitro with p-benzoquinone
      (BQ). We find, as relative values normalized to 100% of adducts observed, 79% BQ
      dCMP, 21% BQ-methyl-dCMP (a new DNA adduct), and trace amounts of BQ-dAMP and BQ
      dGMP. Because mC is 5% of C in this DNA, the reaction of BQ with DNA in vitro is
      about five times faster at methyl-C than C. When equal amounts of dCMP and methyl
      dCMP are reacted with BQ, equal amounts of the corresponding adducts are
      observed. Thus, the microenvironment of methyl-C in DNA enhances its reactivity
      relative to C with BQ. In a prior, similar study, but based on analysis by (32)P
      postlabeling, the second most abundant adduct was assigned to BQ-A, apparently
      because of comigration of the BQ-A and BQ-methyl-C adducts (as bisphosphates) in
      the chromatographic step. Because the calf thymus DNA (used as received) was
      contaminated with RNA, we also detected the ribonucleotide adduct, BQ-CMP.

PMID- 23113580
TI  - Highly stereoselective and scalable synthesis of trans-fused
      octahydrocyclohepta[b]pyrrol-4(1H)-ones via the aza-Cope-Mannich rearrangement in
      racemic and enantiopure forms.
AB  - We have developed an efficient and stereoselective route to trans-fused
      octahydrocyclohepta[b]pyrrol-4(1H)-ones. The key features of our synthesis
      include the regioselective epoxide ring-opening of alkynyl oxiranes and a
      stereoselective aza-Cope-Mannich reaction. The target compounds were prepared in
      3-6 steps from commercially available starting materials (61-75% overall yield)
      with minimal chromatographic purification. We have devised an stereoselective
      route to target compounds using Shi epoxidation or (R)-1-phenylethylamine as a
      source of chirality.

PMID- 23113582
TI  - Coconut kernel-derived proteins enhance hypolipidemic and antioxidant activity in
      alloxan-induced diabetic rats.
AB  - Impaired lipid levels and oxidative stress are indicative of malfunction of
      endogenous antioxidant capacity. The aim of this study was to determine the
      effect of coconut kernel protein (CKP) on the lipid peroxides and antioxidant
      enzyme activities in diabetic rats. Diabetes was induced prior to feeding by
      injecting a single dose of alloxan (150 mg/kg body weight) intraperitoneally. CKP
      (8% w/w) was administered to these rats along with a semi-synthetic diet for 45
      days. After the experimental period, peroxide products and antioxidant enzyme
      activities were determined. Results show that CKP maintained the antioxidant
      enzyme activities and levels of peroxides to the normal levels in treated group
      compared to diabetic rats. This study clearly show that CKP has potential effect
      in lowering oxidative stress associated with diabetes. This beneficial effect of
      CKP may be due to the high amount of biologically potent arginine present in it.

PMID- 23113581
TI  - Antitumor effects of EGFR antisense guanidine-based peptide nucleic acids in
      cancer models.
AB  - Peptide nucleic acids have emerged over the past two decades as a promising class
      of nucleic acid mimics because of their strong binding affinity and sequence
      selectivity toward DNA and RNA, and resistance to enzymatic degradation by
      proteases and nucleases. While they have been shown to be effective in regulation
      of gene expression in vitro, and to a small extent in vivo, their full potential
      for molecular therapy has not yet been fully realized due to poor cellular
      uptake. Herein, we report the development of cell-permeable, guanidine-based
      peptide nucleic acids targeting the epidermal growth factor receptor (EGFR) in
      preclinical models as therapeutic modality for head and neck squamous cell
      carcinoma (HNSCC) and nonsmall cell lung cancer (NSCLC). A GPNA oligomer, 16
      nucleotides in length, designed to bind to EGFR gene transcript elicited potent
      antisense effects in HNSCC and NSCLC cells in preclinical models. When
      administered intraperitoneally in mice, EGFRAS-GPNA was taken-up by several
      tissues including the xenograft tumor. Systemic administration of EGFRAS-GPNA
      induced antitumor effects in HNSCC xenografts, with similar efficacies as the FDA
      approved EGFR inhibitors: cetuximab and erlotinib. In addition to targeting wild
      type EGFR, EGFRAS-GPNA is effective against the constitutively active EGFR vIII
      mutant implicated in cetuximab resistance. Our data reveals that GPNA is just as
      effective as a molecular platform for treating cetuximab resistant cells,
      demonstrating its utility in the treatment of cancer.

PMID- 23113583
TI  - Does menopause influence nocturnal awakening with headache?
AB  - OBJECTIVE: The aim of the present study was to assess whether menopausal status
      influences the occurrence of nocturnal awakening with headache (NAH) in the
      female population of Sao Paulo, Brazil. We also examined the relationship of this
      complaint to sociodemographic determinants, hot flushes, sleep quality and
      parameters, anxiety and depressive symptoms, somnolence and fatigue according to
      menopausal status. METHODS: The female population of the Sao Paulo Epidemiologic
      Sleep Study (EPISONO) (n = 576) was divided according to menopausal status (pre-,
      peri-, early and late menopause) based on questionnaires and hormonal blood
      measures. The complaint of waking up because of a headache at least once a week
      was assessed by the UNIFESP Sleep questionnaire. Additionally, hot flushes, sleep
      complaints, anxiety and depressive symptoms, somnolence and fatigue were assessed
      by specific questionnaires. A full-night polysomnography assessed sleep
      parameters. RESULTS: The prevalence of NAH in women in the Sao Paulo population
      was 13.3%. Perimenopause was associated with a higher risk of having NAH (odds
      ratio 13.9; 95% confidence interval 4.3-45.2). More complaints of NAH were
      observed in obese women. All the groups with NAH showed more hot flushes, worse
      subjective sleep quality, more complaints of insomnia, anxiety symptoms and
      fatigue. CONCLUSIONS: We observed a constellation of symptoms in women according
      to menopausal status and NAH that included hot flushes, sleep complaints, more
      anxiety symptoms and fatigue. Moreover, some of these symptoms were more frequent
      in perimenopausal women with NAH. Therefore, we concluded that menopausal status
      influences NAH and the women in perimenopause presented a high risk of having
      this complaint.

PMID- 23113584
TI  - Fabrication of porous nanocomposites with controllable specific surface area and
      strength via suspension infiltration.
AB  - Porous ceramics are promising candidates for a variety of applications, including
      separation membranes, catalyst supports, tissue engineering scaffolds, energy
      storage devices, and microelectronics. We describe a novel method for creating
      porous ceramics with controllable specific surface area and high strength. The
      fabrication procedure involves infiltrating aqueous suspensions of silica
      nanoparticles into a porous ceramic scaffold. The samples are then freeze-dried
      to maintain a homogeneous distribution of nanoparticles, followed by partial
      sintering to bond the infiltrated nanoparticles into place. By repeating this
      infiltration process multiple times, the specific surface area of the composite
      can be varied from less than one to well over 100 m(2)/g. It is also found that
      this infiltration increases the mechanical strength of the composite. Water flux
      experiments demonstrate the potential use of these materials as liquid membranes,
      with no detectable damage to the structure observed after these flux tests. While
      this initial work focused on silica nanoparticles and ceramic scaffolds, the
      basic approach would to applicable to a wide variety of other materials, meaning
      that the method described here would be generally applicable for creating porous
      materials with precisely controllable properties.

PMID- 23113585
TI  - Design of a three-dimensional multitarget activity landscape.
AB  - The design of activity landscape representations is challenging when compounds
      are active against multiple targets. Going beyond three or four targets, the
      complexity of underlying activity spaces is difficult to capture in conventional
      activity landscape views. Previous attempts to generate multitarget activity
      landscapes have predominantly utilized extensions of molecular network
      representations or plots of activity versus chemical similarity for pairs of
      active compounds. Herein, we introduce a three-dimensional multitarget activity
      landscape design that is based upon principles of radial coordinate
      visualization. Circular representations of multitarget activity and chemical
      reference space are combined to generate a spherical view into which compound
      sets are projected for interactive analysis. Interpretation of landscape content
      is facilitated by following three canonical views of activity, chemical, and
      combined activity/chemical space, respectively. These views focus on different
      planes of the underlying coordinate system. From the activity and combined views,
      compounds with well-defined target selectivity and structure-activity profile
      relationships can be extracted. In the activity landscape, such compounds display
      characteristic spatial arrangements and target activity patterns.

PMID- 23113586
TI  - Excitons and excess electrons in nanometer size molecular polyoxotitanate
      clusters: electronic spectra, exciton dynamics, and surface states.
AB  - The behavior of excitons and excess electrons in the confined space of a
      molecular polyoxotitanate cluster Ti17(MU4-O)4(MU3-O)16(MU2-O)4(OPr(i))20 (in
      short Ti17) was studied using femtosecond pump-probe transient absorption, pulse
      radiolysis, and fluorescence spectroscopy. Due to pronounced quantum size
      effects, the electronic spectra of the exciton, Ti17*, and the excess electron
      carrying radical anion, Ti17(*-), are blue-shifted in comparison with bulk TiO2
      and have maxima at 1.91 and 1.24 eV, respectively. The 0.7 eV difference in the
      position of the absorption maxima of Ti17* and Ti17(*-) indicates the presence of
      strong Coulomb interaction between the conduction band electron and the valence
      band hole in the ~1 nm diameter cluster. Ground state Raman spectra and the
      vibronic structure of the fluorescence spectrum point to the importance of the
      interfacial ligand modes in the stabilization and localization of the fully
      relaxed exciton. Four pentacoordinate Ti sites near the surface of the cluster
      appear to play a special role in this regard. Solvent polarity has only a minor
      influence on the spectral behavior of Ti17*. Exciton recombination in Ti17 is
      faster than in anatase nanoparticles or mesoporous films. The kinetics exhibits
      three components, ranging from less than 1 ps to 100 ps, which are tentatively
      assigned to the geminate recombination within the core of the cluster and to the
      decay of the surface stabilized charge transfer exciton. A persistent long-lived
      component with tau > 300 ps may indicate the involvement of intraband dark
      states, i.e., triplet excitons (3)Ti17*.

PMID- 23113587
TI  - Gifts from the tropics.

PMID- 23113588
TI  - Complement 5a stimulates hepatic stellate cells in vitro, and is increased in the
      plasma of patients with chronic hepatitis B.
AB  - Complement 5a (C5a) is a critical modulator of liver immunity. In this study, we
      investigated the role of C5a and its receptor in liver fibrosis in patients with
      hepatitis B virus infection. We found that plasma C5a concentration was
      significantly increased in patients with chronic hepatitis B, particularly in
      those patients with higher grade and stage scores. Further analysis indicated
      that the increased C5a concentration was positively correlated with clinical
      parameters reflecting liver fibrosis severity, including type IV collagen and
      procollagen type III N-terminal peptide. Our in vitro data indicated that the C5a
      receptor is highly expressed in hepatic stellate cells (HSCs). Addition of C5a
      significantly activated HSCs and up-regulated alpha-smooth muscle actin,
      hyaluronic acid and type IV collagen expression. Also, addition of C5a could
      inhibit the spontaneous and soluble tumour necrosis factor-related apoptosis
      inducing ligand-induced apoptosis of HSCs. These findings highlight the potential
      role of C5a in the regulation of liver fibrosis.

PMID- 23113589
TI  - Improvement in skin color achieved by smoking cessation.
AB  - It has been well known that habitual smoking accelerates premature skin ageing
      recognized as 'smoker's face'. However, the effect of smoking cessation on the
      appearance of skin has not been elucidated. The aim of this study was to evaluate
      objectively the effect of smoking cessation on the skin's appearance. The stratum
      corneum carbonyl protein level and skin colour of the cheek and the hand were
      measured. The change before and during the smoking cessation treatment (0, 2, 4,
      8 and 12 weeks), and the success or failure in smoking cessation, was compared
      and examined. Eighty-four cases who had smoking cessation treatment were
      examined. The level of the stratum corneum carbonyl protein did not show any
      difference comparing before and after treatment for the smoking cessation success
      group and the failure group. The lightness of skin colour showed an upward
      tendency 4-12 weeks after starting the treatment in the success group and
      increased significantly compared with the failure group. The redness showed a
      significant decrease in comparison with before the treatment, and it also showed
      a significant decrease compared with the failure group. The yellowness did not
      show any clear tendency. Also, the haemoglobin showed a decreased tendency.
      Furthermore, multivariate statistical analysis showed a possibility that the
      lightness and haemoglobin could be changed by smoking cessation treatment. In
      conclusion, our study showed that an upward tendency of skin lightness was seen
      to correspond with a haemoglobin decrease accompanied by smoking cessation. If we
      can easily measure skin improvement as an effect of smoking cessation, it is
      thought to be a useful aid for smoking cessation support.

PMID- 23113590
TI  - Long-term complete remission in a multiple myeloma patient after Stevens-Johnson
      syndrome due to lenalidomide therapy.

PMID- 23113591
TI  - Integrated peripheral boost in preoperative radiotherapy for the locally most
      advanced non-resectable rectal cancer patients.
AB  - BACKGROUND AND PURPOSE: Few studies have explored the potential clinical
      advantages of dose escalation and integrated boosts for patients with non
      resectable locally advanced rectal cancer. The possibility of escalating dose to
      non-resectable regions in these patients was the aim of this study. PATIENTS AND
      METHODS: Seven patients with locally very advanced rectal tumours (sacrum
      overgrowth or growth into pelvic side walls) were evaluated. Intensity modulated
      photon and pencil beam scanning proton plans with simultaneously integrated
      boosts (45 Gy to elective lymph nodes, 50 Gy to tumour and 62.5 Gy to boost area
      in 25 fractions) were compared. RESULTS: Target coverage was achieved with both
      photon and proton plans. Estimated risks of acute side effects put the two
      patients with the largest tumours at unacceptable risk for intestinal toxicity,
      regardless of modality. The remaining five patients had beneficial sparing of
      dose to the small intestine with protons. CONCLUSIONS: Adding boost to areas
      where rectal tumours infiltrate adjacent non-resectable organs is an attractive
      option which appears possible using both photon and proton irradiation. Proton
      plans reduced dose to organs at risk. Integrated peripheral boosts should be
      considered more frequently in these very advanced tumours.

PMID- 23113592
TI  - Dose-response relationships for an atomized symptom of fecal incontinence after
      gynecological radiotherapy.
AB  - PURPOSE: The aim of this study was to investigate what bowel organ and delivered
      dose levels are most relevant for the development of 'emptying of all stools into
      clothing without forewarning' so that the related dose-responses could be derived
      as an aid in avoiding this distressing symptom in the future. MATERIAL AND
      METHODS: Of the 77 gynecological cancer survivors treated with radiotherapy (RT)
      for gynecological cancer, 13 developed the symptom. The survivors were treated
      between 1991 and 2003. The anal-sphincter region, the rectum, the sigmoid and the
      small intestines were all delineated and the dose-volume histograms were exported
      for each patient. The dose-volume parameters were estimated fitting the data to
      the Relative Seriality (RS), the Lyman and the generalized Equivalent Uniform
      Dose (gEUD) model. RESULTS: The dose-response parameters for all three models and
      four organs at risk (OARs) were estimated. The data from the sigmoid fits the
      studied models best: D50 was 58.8 and 59.5 Gy (RS, Lyman), gamma50 was 1.60 and
      1.57 (RS, Lyman), s was 0.32, n was 0.13 and a was 7.7 (RS, Lyman, gEUD). The
      estimated volume parameters indicate that the investigated OARs behave serially
      for this endpoint. Our results for the three models studied indicate that they
      have the same predictive power (similar LL values) for the symptom as a function
      of the dose for all investigated OARs. CONCLUSIONS: In our study, the anal
      sphincter region and sigmoid fit our data best, but all OARs were found to have
      steep dose-responses for 'emptying of all stools into clothing without
      forewarning' and thus, the outcome can be predicted with an NTCP model. In
      addition, the dose to the four studied OARs may be considered when minimizing the
      risk of the symptom.

PMID- 23113593
TI  - Do patients trust their physician? The role of attachment style in the patient
      physician relationship within one year after a cancer diagnosis.
AB  - BACKGROUND: The degree of trust in and satisfaction with the physician has been
      shown to have important implications for treatment outcomes. This study aims to
      examine individual differences in patients' trust, satisfaction and general
      distress from an attachment theoretical perspective. MATERIAL AND METHODS: One
      hundred and thirty recently diagnosed cancer patients of three medical hospitals
      were extensively interviewed by trained psychologists to assess attachment style.
      Patients completed standardized questionnaires three and nine months after
      diagnosis to assess trust, satisfaction and distress. t-tests and repeated
      measures ANOVAs were used to examine differences between securely and insecurely
      attached patients and changes over time. A mediation model based on a
      bootstrapping method was used to examine whether trust mediated between
      attachment and satisfaction, and attachment and distress. RESULTS: Insecurely
      attached patients (N = 45, 35%) reported less trust in and satisfaction with
      their physician, and reported more general distress than securely attached
      patients three and nine months after diagnosis (p < 0.05). Trust and distress
      levels did not change over time. Trust mediated between attachment and
      satisfaction, but not between attachment and distress. CONCLUSION: Insecurely
      attached patients trusted their physician less than securely attached patients,
      and in turn were less satisfied with their physician. Their higher levels of
      general distress were not related to their lower levels of trust. Attachment
      theory provides a framework to interpret differences in patients' trust,
      satisfaction and distress, and may help physicians respond in such a way that
      their patients feel secure, which in turn is expected to result in better health
      outcomes.

PMID- 23113594
TI  - Luminescent properties of ruthenium(II) complexes with sterically expansive
      ligands bound to DNA defects.
AB  - A new family of ruthenium(II) complexes with sterically expansive ligands for
      targeting DNA defects was prepared, and their luminescent responses to base pair
      mismatches and/or abasic sites were investigated. Design of the complexes sought
      to combine the mismatch specificity of sterically expansive metalloinsertors,
      such as [Rh(bpy)2(chrysi)](3+) (chrysi = chrysene-5,6-quinone diimine), and the
      light switch behavior of [Ru(bpy)2(dppz)](2+) (dppz = dipyrido[3,2-a:2',3'
      c]phenazine). In one approach, complexes bearing analogues of chrysi
      incorporating hydrogen-bonding functionality similar to dppz were synthesized.
      While the complexes show luminescence only at low temperatures (77 K),
      competition experiments with [Ru(bpy)2(dppz)](2+) at ambient temperatures reveal
      that the chrysi derivatives preferentially bind DNA mismatches. In another
      approach, various substituents were introduced onto the dppz ligand to increase
      its steric bulk for mismatch binding while maintaining planarity. Steady state
      luminescence and luminescence lifetime measurements reveal that these dppz
      derivative complexes behave as DNA "light switches" but that the selectivity in
      binding and luminescence with mismatched/abasic versus well-matched DNA is not
      high. In all cases, luminescence depends sensitively upon structural
      perturbations to the dppz ligand. 

PMID- 23113595
TI  - Compton scattering by internal shields based on melanin-containing mushrooms
      provides protection of gastrointestinal tract from ionizing radiation.
AB  - There is a need for radioprotectors that protect normal tissues from ionizing
      radiation in patients receiving high doses of radiation and during nuclear
      emergencies. We investigated the possibility of creating an efficient oral
      radioprotector based on the natural pigment melanin that would act as an internal
      shield and protect the tissues via Compton scattering followed by free radical
      scavenging. CD-1 mice were fed melanin-containing black edible mushrooms
      Auricularia auricila-judae before 9 Gy total body irradiation. The location of
      the mushrooms in the body before irradiation was determined by in vivo
      fluorescent imaging. Black mushrooms protected 80% of mice from the lethal dose,
      while control mice or those given melanin-devoid mushrooms died from
      gastrointestinal syndrome. The crypts of mice given black mushrooms showed less
      apoptosis and more cell division than those in control mice, and their white
      blood cell and platelet counts were restored at 45 days to preradiation levels.
      The role of melanin in radioprotection was proven by the fact that mice given
      white mushrooms supplemented with melanin survived at the same rate as mice given
      black mushrooms. The ability of melanin-containing mushrooms to provide
      remarkable protection against radiation suggests that they could be developed
      into oral radioprotectors.

PMID- 23113596
TI  - Bax is essential for death receptor-mediated apoptosis in human colon cancer
      cells.
AB  - To demonstrate the role of Bax in death receptor-induced apoptosis in the human
      colon cancer HCT116 cells. We treated HCT116 cells and HCT116 with p53(-/-) (KO)
      by 0.1 MUg/mL TRAIL for 24 hours, which indicated that HCT116 parental cells are
      sensitive to p53-independent death receptor-induced apoptosis. Although the p53
      signaling pathway is totally intact in this system, the down-regulation of Bax in
      HCT116 cells is dramatically resistant to TRAIL and failed to undergo apoptosis.
      However, the over-expression of Bax can rescue the sensitivity of apoptosis
      induced by the death receptor. Our study has revealed an essential role for Bax
      in death receptor-induced apoptosis in the human colon cancer HCT116 cells. It
      may aid in a molecular understanding of possible defects in signal transduction
      and a regulation of the death receptor-induced apoptotic process.

PMID- 23113597
TI  - The prognostic accuracy of resonance frequency analysis in predicting failure
      risk of immediately restored implants.
AB  - OBJECTIVES: It is of imperative clinical significance to define a safe threshold
      for planned immediate implant restoration. The aim of this report was to evaluate
      the prognostic accuracy of resonance frequency analysis (RFA) measurements
      recorded at two different times (implant placement and 8-week post-implant
      placement) and to determine the optimal threshold value for predicting failure
      risk of immediately restored/loaded implants. MATERIAL AND METHODS: Twenty-eight
      8- or 9-mm-diameter implants were placed in either a fresh molar extraction
      socket or a healed site. An electronic RFA device was used to record the implant
      stability quotients (ISQs) at implant placement surgery, 8 weeks and 1 year.
      Receiver operating characteristic (ROC) analysis was used to identify the optimal
      cut-off level. Sensitivity and specificity were also determined at the selected
      cut-off value. RESULTS: The area under the ROC curve for RFA at 8 weeks was 0.93
      with a significant P-value (P = 0.001). The optimum cut-off value for detecting
      implant stability was 60.5 ISQ measured at 8 weeks, with sensitivity and
      specificity of 95.2% and 71.4%, respectively. CONCLUSIONS: The implant stability
      measurements after 8 weeks showed a better accuracy in predicting implants that
      were at risk of failure than those taken at the time of implant placement.

PMID- 23113598
TI  - Association between endothelial nitric oxide synthase Glu298Asp gene polymorphism
      and diabetic nephropathy susceptibility.
AB  - The association between endothelial nitric oxide synthase (eNOS) Glu298Asp gene
      polymorphism and diabetic nephropathy (DN) risk is still controversial. A meta
      analysis was performed to evaluate the association between eNOS Glu298Asp gene
      polymorphism and DN susceptibility. A predefined literature search and selection
      of eligible relevant studies were performed to collect data from electronic
      database. Eight articles were identified for the analysis of association between
      eNOS Glu298Asp gene polymorphism and DN risk. T allele was associated with DN
      susceptibility in overall populations, in Asians, and for Caucasians (overall
      populations, p = 0.005; Asians, p = 0.004; Caucasians, p = 0.002). Furthermore,
      GG genotype might play a protective role against DN onset for overall
      populations, Asians, Caucasians, and Africans. However, a link between eNOS
      Glu298Asp gene polymorphism and DN risk was not found in overall populations,
      Asians, Caucasians, and Brazil population. In conclusion, T allele might become a
      significant genetic molecular marker for the onset of DN in overall populations,
      in Asians, and for Caucasians. However, more studies should be performed in the
      future.

PMID- 23113599
TI  - A biomechanical model to simulate the effect of a high vertical loading on trunk
      flexural stiffness.
AB  - A human trunk model was developed to simulate the effect of a high vertical
      loading on trunk flexural stiffness. A force-length relationship is attributed to
      each muscle of the multi-body model. Trunk stiffness and muscle forces were
      evaluated experimentally and numerically for various applied loads. Experimental
      evaluation of trunk stiffness was carried out by measuring changes in reaction
      force following a sudden horizontal displacement at the T10 level prior to
      paraspinal reflexes induction. Results showed that the trunk stiffness increases
      under small applied loads, peaks when the loads were further increased and
      decreases when higher loads are applied. A sensitivity analysis to muscle force
      length relationship is provided to determine the model's limitations. This model
      pointed out the importance of taking into account the changes in muscle length to
      evaluate the effect of spinal loads beyond the safe limit that cannot be
      evaluated experimentally and to predict the trunk instability under vertical
      load. 

PMID- 23113600
TI  - Multipoint interactions enhanced CO2 uptake: a zeolite-like zinc-tetrazole
      framework with 24-nuclear zinc cages.
AB  - A zeolite-like microporous tetrazole-based metal-organic framework (MOF) with 24
      nuclear zinc cages was synthesized and characterized. It exhibits high CO(2)
      adsorption capacity up to 35.6 wt % (8.09 mmol/g) and excellent CO(2)/CH(4)
      selectivity at 273 K/1 bar, being among the highest values known to date.
      Theoretical calculations based on simulated annealing techniques and periodic DFT
      revealed that CO(2) is predominantly located around the inner surface of the
      cages through multipoint interactions, in particular, around the aromatic
      tetrazole rings. Importantly, it is the first time that multipoint interactions
      between CO(2) molecules and frameworks resulting in high CO(2) uptake are
      observed.

PMID- 23113601
TI  - A case study on decontamination of a biosafety level-3 laboratory and associated
      ductwork within an operational building using gaseous chlorine dioxide.

PMID- 23113602
TI  - Are homology models sufficiently good for free-energy simulations?
AB  - In this paper, I evaluate the usefulness of protein homology models in rigorous
      free-energy simulations to determine ligand affinities. Two templates were used
      to create models of the factor Xa protein and one template was used for
      dihydrofolate reductase from  Plasmodium falciparum.  Then, the relative free
      energies for several pairs of ligands were estimated using thermodynamic
      integration with the homology models as starting point of the simulation. These
      binding affinities were compared to affinities obtained when using published
      crystal structures as starting point of the simulations. Encouragingly, the
      differences between the affinities obtained when starting from either homology
      models or crystal structure were not statistical significant for a majority of
      the considered pairs of ligands. Differences between 1 and 2 kJ/mol were observed
      for the dihydrofolate reductase ligands and differences between 0 and 8 kJ/mol
      were observed for the factor Xa ligands. The largest difference for factor Xa was
      caused by an erroneous modeling of a loop region close to two of the ligands, and
      it was only observed when using one of the templates. Therefore, it is advisible
      to always use more than one template when creating homology models if they should
      be used in free-energy simulations.

PMID- 23113603
TI  - Darbepoetin alfa in the treatment of anemia in cancer patients undergoing
      chemotherapy.
AB  - For years, the treatment of chemotherapy-induced anemia (CIA) consisted of red
      blood cell transfusions. Major disadvantages of transfusions are their temporary
      effect and limitation to treatment of severe anemia. In an extensive clinical
      trial program in patients with CIA, darbepoetin alfa (DA) - a long-acting
      recombinant human erythropoietin - was proven to be very effective in reducing
      transfusion needs in patients developing CIA. The administration is suitable with
      most chemotherapy schemes. Caution is needed in patients with a history of
      thrombo-embolic events, as a slightly higher incidence of these events is noted
      in patients treated with darbepoetin alfa or erythropoietin substitution agents
      (ESAs) in general. In recent years, concerns have been raised about a potential
      negative influence of these agents on survival. In this respect, it is important
      to make the distinction between studies on the treatment of existing CIA versus
      treatment with ESAs outside this indication. On the other hand, it has always
      been assumed that transfusions were a completely safe treatment, but concerns
      about a potential negative effect on survival have been raised for transfusions
      as well. The safety concerns with DA and ESAs in general led to a
      pharmacovigilance program and an adaptation of the guidelines for treatment of
      CIA, focusing on treatment of moderate CIA but no longer on mild CIA. Now that
      the most recent safety data of the pharmacovigilance program of ESAs is almost
      completed, the clinical impact of the shift to the treatment of only moderate
      anemia is discussed in this review, which provides a critical view on the
      indications of DA and the benefit-risk assessment, in order to provide good
      supportive care without harm to the patient.

PMID- 23113604
TI  - Third generation photovoltaics based on multiple exciton generation in quantum
      confined semiconductors.
AB  - Improving the primary photoconversion process in a photovoltaiccell by utilizing
      the excess energy that is otherwise lost as heat can lead to an increase in the
      overall power conversion efficiency (PCE). Semiconductor nanocrystals (NCs) with
      at least one dimension small enough to produce quantum confinement effects
      provide new ways of controlling energy flow not achievable in thin film or bulk
      semiconductors. Researchers have developed various strategies to incorporate
      these novel structures into suitable solar conversion systems. Some of these
      methods could increase the PCE past the Shockley-Queisser (SQ) limit of ~33%,
      making them viable "third generation photovoltaic" (TGPV) cell architectures.
      Surpassing the SQ limit for single junction solar cells presents both a
      scientific and a technological challenge, and the use of semiconductor NCs to
      enhance the primary photoconversion process offers a promising potential
      solution. The NCs are synthesized via solution phase chemical reactions producing
      stable colloidal solutions, where the reaction conditions can be modified to
      produce a variety of shapes, compositions, and structures. The confinement of the
      semiconductor NC in one dimension produces quantum films, wells, or discs. Two
      dimensional confinement leads to quantum wires or rods (QRs), and quantum dots
      (QDs) are three-dimensionally confined NCs. The process of multiple exciton
      generation (MEG) converts a high-energy photon into multiple electron-hole pairs.
      Although many studies have demonstrated that MEG is enhanced in QDs compared with
      bulk semiconductors, these studies have either used ultrafast spectroscopy to
      measure the photon-to-exciton quantum yields (QYs) or theoretical calculations.
      Implementing MEG in a working solar cell has been an ongoing challenge. In this
      Account, we discuss the status of MEG research and strategies towards
      implementing MEG in working solar cells. Recently we showed an external quantum
      efficiency for photocurrent of greater than 100% (reaching 114%) at ~4Eg in a
      PbSe QD solar cell. The internal quantum efficiency reached 130%. These results
      compare favorably with ultrafast transient spectroscopic measurements. Thus, we
      have shown that one of the tenets of the SQ limit, that photons only produce one
      electron-hole pair at the electrodes of a solar cell, can be overcome. Further
      challenges include increasing the MEG efficiency and improving the QD device
      structure and operation.

PMID- 23113605
TI  - Clinical impact of inappropriate initial antimicrobial therapy on outcome in
      bacteremic biliary tract infections.
AB  - BACKGROUND: The marked increase in the incidence of biliary tract infections due
      to antimicrobial-resistant pathogens in recent years is of great concern, as
      patients infected by these isolates might initially receive antibiotics
      ineffective against the responsible pathogens. METHODS: A retrospective cohort
      study including 556 episodes of bacteremic biliary tract infection was designed
      to evaluate the impact of inappropriate initial antimicrobial therapy on the
      clinical outcomes of patients with biliary tract infections. RESULTS: Of 556
      episodes, 257 (46.2%) received inappropriate initial antimicrobial therapy.
      Although Escherichia coli and Klebsiella species are the most common pathogens,
      the pathogens that were most frequently associated with inappropriate therapy
      were Pseudomonas aeruginosa and Enterococcus spp. In multivariable analysis,
      inappropriate initial antimicrobial therapy was found to be independently
      associated with increased mortality (odds ratio (OR) 2.25, 95% confidence
      interval (CI) 1.13-4.48; p = 0.021), along with pancreaticobiliary tract cancer,
      liver cirrhosis, Enterobacter infection, and a high Pitt bacteremia score (All p
      < 0.05). Subgroup multivariate analyses showed that inappropriate initial therapy
      was not a significant factor associated with mortality in cases where therapeutic
      decompression or drainage procedures were employed (OR 1.24, 95% CI 0.43-3.54; p
      = 0.691) or in cases with appropriate definitive antimicrobial therapy (OR 1.61,
      95% CI 0.69-3.72; p = 0.270) after adjustment for other variables. CONCLUSIONS:
      Our findings suggest that the administration of inappropriate initial
      antimicrobial therapy might be associated with an adverse outcome in patients
      experiencing bacteremic biliary tract infections, and that the impact of
      inappropriate therapy on the outcome may be dependent on therapeutic drainage and
      appropriate definitive antimicrobial therapy.

PMID- 23113606
TI  - Lack of an association between left-handedness and APOE polymorphism in a large
      sample of adults: results of the Czech HAPIEE study.
AB  - An association between APOE genotype and left-handedness has been previously
      reported. We examined whether such association exists in a population sample of
      4438 unrelated Caucasian adults aged 45-69 years (2022 males and 2416 females).
      Left-handedness was based on self-reported left-hand dominance for writing
      (prevalence 4.9%) and on consistently higher left-hand grip strength in two
      repeated measurements (prevalence 12.2%). Individuals with higher left hand grip
      strength were seven times more likely to be self-reported left handers (p<.0001,
      chi(2) 159.7, 2 df). There were no differences in the proportion of self-reported
      left-handedness (p=.828, chi(2) 2.1, 5 df) or higher grip strength in left hand
      (p=.557, chi(2) 3.9, 5 df) between APOE genotypes. The lack of association was
      similar in both genders and did not differ by age group. The results suggest that
      left-handedness in adults is not related to APOE genotype. 

PMID- 23113607
TI  - Unusual localization of a common cutaneous neoplasm: basal cell carcinoma.
AB  - Basal cell carcinoma (BCC) is the most common form of the skin carcinomas and
      ultraviolet radiation is the major risk factor in the etiopathogenesis. However,
      reports of unusual sites for BCC are increased in the literature. Authors draw
      attention to possibility of other etiological agents for BCC like local trauma,
      ageing, ionizing radiation, arsenic, chronic inflammation, and immune deficiency.
      Here, we reported a 74-year-old male patient with nodular BCC on groin. We
      thought that ageing or local trauma may have a role in its formation.

PMID- 23113608
TI  - Quantitative mapping of the elastic modulus of soft materials with HarmoniX and
      PeakForce QNM AFM modes.
AB  - The modulus of elasticity of soft materials on the nanoscale is of interest when
      studying thin films, nanocomposites, and biomaterials. Two novel modes of atomic
      force microscopy (AFM) have been introduced recently: HarmoniX and PeakForce QNM.
      Both modes produce distribution maps of the elastic modulus over the sample
      surface. Here we investigate the question of how quantitative these maps are when
      studying soft materials. Three different polymers with a macroscopic Young's
      modulus of 0.6-0.7 GPa (polyurethanes) and 2.7 GPa (polystyrene) are analyzed
      using these new modes. The moduli obtained are compared to the data measured with
      the other commonly used techniques, dynamic mechanical analyzer (DMA), regular
      AFM, and nanoindenter. We show that the elastic modulus is overestimated in both
      the HarmoniX and PeakForce QNM modes when using regular sharp probes because of
      excessively overstressed material in the samples. We further demonstrate that
      both AFM modes can work in the linear stress-strain regime when using a
      relatively dull indentation probe (starting from ~210 nm). The analysis of the
      elasticity models to be used shows that the JKR model should be used for the
      samples considered here instead of the DMT model, which is currently implemented
      in HarmoniX and PeakForce QNM modes. Using the JKR model and ~240 nm AFM probe in
      the PeakForce QNM mode, we demonstrate that a quantitative mapping of the elastic
      modulus of polymeric materials is possible. A spatial resolution of ~50 nm and a
      minimum 2 to 3 nm indentation depth are achieved.

PMID- 23113609
TI  - Heterotopic brain tissue on the face and neck in a neonate: a rare case report
      and literature review.
AB  - Heterotopic brain tissue (HBT) most commonly occurs in the nasal region and it is
      often referred to as a nasal glioma. Nonnasal locations for ectopic brain tissue
      are less commonly described. In English literature, only six cases have been
      reported that share some features (face or neck location) of this case. The
      presented case is the fourth case, located in both face and neck, and the one,
      which is the most extensive with its dimensions. According to location of
      heterotopic brain may lead to dystocia. We reported HBT of the face and neck in a
      neonate and the differential diagnosis, etiopathogenic mechanisms and clinical
      courses are reviewed and discussed.

PMID- 23113610
TI  - Cooperative effects in inelastic tunneling.
AB  - Several aspects of intermolecular effects in molecular conduction have been
      studied in recent years. These experimental and theoretical studies, made on
      several setups of molecular conduction junctions, have focused on the current
      voltage characteristic that is usually dominated by the elastic transmission
      properties of such junctions. In this paper, we address cooperative
      intermolecular effects in the inelastic tunneling signal calculated for simple
      generic models of such systems. We find that peak heights in the inelastic
      (d(2)I/dE(2) vs E) spectrum may be affected by such cooperative effects even when
      direct intermolecular interactions can be disregarded. This finding suggests that
      comparing experimental results to calculations made on single-molecule junctions
      should be done with care.

PMID- 23113611
TI  - Cellular and animal indispensable amino acid limitation responses and health
      promotion. Can the two be linked? A critical review.
AB  - Cellular growth repression can mediate positive health outcomes by improving
      resistance while delaying the manifestation and decelerating the progression, of
      chronic diseases. Sensing systems that respond to amino acid limitation are, the
      general control non-derepressible kinase 2 (GCN2), the mammalian target of
      rapamycin (mTOR; namely mammalian target of rapamycin complex 1), the
      extracellular signal-regulated kinase (ERK)-mitogen-activated protein kinase
      pathway, the adenosine 5-mono-phosphate-activated protein kinase system. GCN2
      particularly, under limiting essential amino acid conditions, activates the
      integrated stress response (ISR) causing selective up- /down-regulation of pro
      survival/pro-apoptotic genes, respectively, rendering beneficial adaptation
      responses to amino acid limitation. This review attempts to bridge the link
      between molecular events and mechanisms observed at the cellular level with the
      potential health benefits possibly achieved at the whole organism level. The
      article describes mechanisms of essential amino acid sensing and provides a
      discussion on relevant research that suggests a potential role of essential amino
      acid sensing for promoting health.

PMID- 23113612
TI  - Annular elastolytic giant cell granuloma developing on lesions of vitiligo.

PMID- 23113613
TI  - Clinical characteristics of eosinophilic and noneosinophilic asthma in children.
AB  - AIM: Asthma is a heterogeneous and complex chronic inflammatory disease of the
      airways. Asthma can be classified as eosinophilic asthma (EA) or noneosinophilic
      asthma (NEA). We investigated whether children with EA manifest different
      clinical characteristics than those with NEA. METHODS: We enrolled 288 steroid
      naive asthmatic children and classified them, based on the cell counts in induced
      sputum, into EA (158 children) and NEA (89 children) groups. RESULTS: No
      significant differences were observed between the groups with regard to age, sex,
      family history of atopy, secondary smoking or asthma exacerbations. Moderate-to
      severe asthma was more frequent in the EA group than in the NEA group. Blood
      eosinophil counts and serum eosinophil cationic protein were higher in EA
      patients than in NEA patients. The forced expiratory volume in 1 sec was lower in
      children with EA than in those with NEA (% of predicted value, 88.6 +/- 18.5 vs.
      93.6 +/- 15.6, p < 0.05). The sputum eosinophil (in EA) and neutrophil (in NEA)
      counts increased with increasing asthma severity. CONCLUSION: Airway
      inflammation, especially eosinophilic inflammation, was associated with asthma
      severity and reduced pulmonary function in children.

PMID- 23113615
TI  - Azadipyrromethene dye derivatives in coordination chemistry: the structure
      property relationship in homoleptic metal(II) complexes.
AB  - As a chromophore closely related to dipyrromethene (DPM), the azadipyrromethene
      (ADPM) family has attracted much interest in the life sciences and optoelectronic
      fields. A high-yielding microwave-assisted synthesis is reported for new
      homoleptic complexes of cobalt(II), nickel(II), copper(II) and zinc(II) based on
      the tetrakis(p-methoxyphenyl)azadipyrromethene ligand 1b. These complexes are
      compared with other homoleptic complexes of the same metal(II) series based on
      the tetraphenylazadipyrromethene 1a and also with related BF2(+) chelates (Aza
      BODIPYs 6a and 6b) for a better understanding of trends arising from substitution
      of the chelate and/or the electron-donating effect of the p-methoxy substituents.
      The electrochemical behavior of the new compounds 2b, 3b, and 5b in
      dichloromethane revealed two pseudoreversible reductions (2b, -1.09 and -1.25 V
      vs SCE; 3b, -1.05 and -1.29 V; 5b, -1.13 and -1.25 V) followed by a third
      irreversible process (2b, -1.78 V; 3b, -1.80 V; 5b, -1.77 V) along with two
      pseudoreversible oxidations (2b, 0.55 and 0.80 V; 3b, 0.56 and 0.80 V; 5b, 0.55
      and 0.80 V) followed by two closely spaced irreversible processes (2b, 1.21 and
      1.27 V; 3b, 1.21 and 1.28 V; 5b, 1.22 and 1.25 V). On its side, copper(II)
      homoleptic complex 4b revealed only one pseudoreversible reduction at -0.59 V
      followed by three irreversible processes at -0.95, -1.54, and -1.74 V,
      respectively. The oxidation behavior of this complex exhibited two
      pseudoreversible processes (0.55 and 0.82 V) and two irreversible processes (1.19
      and 1.25 V). The redox processes are assigned and discussed in relation to their
      photophysical properties. X-ray structures for 1b and related copper(II) complex
      2b are also discussed. 

PMID- 23113614
TI  - The phagocytic capacity and immunological potency of human dendritic cells is
      improved by alpha2,6-sialic acid deficiency.
AB  - Dendritic cells (DCs) play an essential role in immunity against bacteria by
      phagocytosis and by eliciting adaptive immune responses. Previously, we
      demonstrated that human monocyte-derived DCs (MDDCs) express a high content of
      cell surface alpha2,6-sialylated glycans. However, the relative role of these
      sialylated structures in phagocytosis of bacteria has not been reported. Here, we
      show that treatment with a sialidase significantly improved the capacity of both
      immature and mature MDDCs to phagocytose Escherichia coli. Desialylated MDDCs had
      a significantly more mature phenotype, with higher expression of MHC molecules
      and interleukin (IL)-12, tumour necrosis factor-alpha, IL-6 and IL-10 cytokines,
      and nuclear factor-kappaB activation. T lymphocytes primed by desialylated MDDCs
      expressed more interferon-gamma when compared with priming by sialylated MDDCs.
      Improved phagocytosis required E. coli sialic acids, indicating a mechanism of
      host-pathogen interaction dependent on sialic acid moieties. The DCs harvested
      from mice deficient in the ST6Gal.1 sialyltransferase showed improved
      phagocytosis capacity, demonstrating that the observed sialidase effect was a
      result of the removal of alpha2,6-sialic acid. The phagocytosis of different
      pathogenic E. coli isolates was also enhanced by sialidase, which suggests that
      modifications on MDDC sialic acids may be considered in the development of MDDC
      based antibacterial therapies. Physiologically, our findings shed new light on
      mechanisms that modulate the function of both immature and mature MDDCs, in the
      context of host-bacteria interaction. Hence, with particular relevance to DC
      based therapies, the engineering of alpha2,6-sialic acid cell surface is a novel
      possibility to fine tune DC phagocytosis and immunological potency.

PMID- 23113616
TI  - Human parvovirus B19-induced acute glomerulonephritis: a case report.
AB  - Human parvovirus B19 (HPV B19) infection is well known as a cause of erythema
      infectiosum in children. Acute glomerulonephritis due to HPVB19 infection is
      rarely observed in adults. Here, we present the case of a 45-year-old female who
      showed acute glomerulonephritis induced by HPVB19 infection with various
      autoantibodies. She had proteinuria (175 mg/g creatinine) and hematuria (20-29
      erythrocytes per high-power field) in a urinalysis, and various autoantibodies
      such as antinuclear antibodies, proteinase-3-antineutrophil cytoplasmic
      antibodies (PR3-ANCA), antiglomerular basement membrane (GBM) antibodies, and
      anticardiolipin antibodies in a blood examination. A renal biopsy showed that
      endocapillary proliferative glomerulonephritis comprised of mononuclear cell
      infiltration. By using immunofluorescence microscopy, IgG, IgA, IgM, C3, C4, and
      C1q deposits were detected mainly in glomerular capillaries. Electron-dense
      deposits were detected in the subendothelial area and mesangial area by using
      electron microscopy. All symptoms and abnormal laboratory data were self
      improved. Our patient's case may provide a clue to the etiology of ANCA
      associated vasculitis or lupus nephritis.

PMID- 23113617
TI  - A mathematical model for cell differentiation, as an evolutionary and regulated
      process.
AB  - We introduce an approach which allows one to introduce the concept of cell
      plasticity into models for tissue regeneration. In contrast to most of the recent
      models for tissue regeneration, cell differentiation is considered a gradual
      process, which evolves in time and which is regulated by an arbitrary number of
      parameters. In the current approach, cell differentiation is modelled by means of
      a differentiation state variable. Cells are assumed to differentiate into an
      arbitrary number of cell types. The differentiation path is considered as
      reversible, unless differentiation has fully completed. Cell differentiation is
      incorporated into the partial differential equations (PDEs), which model the
      tissue regeneration process, by means of an advection term in the differentiation
      state space. This allows one to consider the differentiation path of cells, which
      is not possible if a reaction-like term is used for differentiation. The boundary
      conditions, which should be specified for the general PDEs, are derived from the
      flux of the fully non-differentiated cells and from the irreversibility of the
      fully completed differentiation process. An application of the proposed model for
      peri-implant osseointegration is considered. Numerical results are compared with
      experimental data. Potential lines of further development of the present approach
      are proposed. 

PMID- 23113618
TI  - Time-of-flight-secondary ion mass spectrometry method development for high
      sensitivity analysis of acid dyes in nylon fibers.
AB  - A minimally destructive technique for the determination of dyes in finished
      fibers provides an important tool for crime scene and other forensic
      investigations. The analytical power and the minimal sample consumption of time
      of-flight-secondary ion mass spectrometric (TOF-SIMS) analysis provides the
      ability to obtain definitive molecular and elemental information relevant to
      fiber identification, including identification of dyes, from a very small volume
      of sample. For both fiber surface analysis and, with the aid of cryomicrotomy,
      fiber cross-section analysis, TOF-SIMS was used to identify various dyes in
      finished textile fibers. The analysis of C.I. Acid Blue 25 in nylon is presented
      as a representative example. The molecular ion of C.I. Acid Blue 25 with lower
      than 3% on weight-of-fiber (owf) dye loading cannot be identified on dyed nylon
      surfaces by TOF-SIMS using a Bi(3)(+) primary ion beam. Sputtering with C(60)(+)
      provided the ability to remove surface contamination as well as at least
      partially remove Bi-induced damage, resulting in a greatly improved signal-to
      noise ratio for the Acid Blue 25 molecular ion. The use of C(60)(+) for damage
      removal in a cyclic manner along with Bi for data acquisition provided the
      ability to unambiguously identify Acid Blue 25 via its molecular ion at a
      concentration of 0.1% owf from both fiber surfaces and cross sections.

PMID- 23113619
TI  - Encapsulation of lactic acid bacteria in colloidosomes.
AB  - Polymeric colloidosomes encapsulating viable lactic acid bacteria were prepared.
      An aqueous suspension of 153 nm poly(methyl methacrylate-co-butyl acrylate) latex
      particles plus Lactobacillus crispatus was emulsified in a continuous phase of
      sunflower oil. By adding a small amount of ethanol and salt to the oil phase, the
      latex particles at the surface of the emulsion droplets aggregate to form the
      colloidosome shells. The colloidosomes have been examined using optical,
      confocal, and scanning electron microscopies. The viability of the bacteria was
      tested using fluorescent molecular probes. The encapsulated lactic acid bacteria
      were able to metabolize glucose from solution and produce acid albeit at a slower
      rate compared to unencapsulated microbes. This demonstrates transport limitation
      through the colloidosome shell and restriction of the cellular metabolism due to
      encapsulation. Protection of the bacteria by encapsulation in colloidosomes was
      also demonstrated; a significantly larger number of encapsulated bacteria
      maintained viability in simulated stomach conditions compared to unencapsulated
      microbes.

PMID- 23113621
TI  - Application of a simultaneous TGA-DSC thermal analysis system for high-throughput
      screening of catalytic activity.
AB  - We present here the use of a simultaneous TGA/DSC thermal analyzer as a high
      throughput reactor system to measure after calibration the heat of reaction and
      therefore the catalytic activity of heterogeneous catalysts in a fast, reliable
      and reproducible manner. By coupling the gas outlet of the analyzer with a mass
      spectrometer via a heated capillary additional data can be acquired. As a test
      reaction the oxidation of carbon monoxide with synthetic air, using Hopcalite and
      several transition and noble metals as catalysts, was chosen. The setup presented
      allows the rapid sequential screening of about 70 catalysts per day. 

PMID- 23113620
TI  - Neuroprotective effect of melatonin against hypoxia-induced retinal ganglion cell
      death in neonatal rats.
AB  - The purpose of this study was to determine whether melatonin treatment would
      mitigate retinal ganglion cell (RGC) death in the developing retina following a
      hypoxic insult. Lipid peroxidation (LPO), glutathione (GSH), tumor necrosis
      factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) concentrations,
      expression of vascular endothelial growth factor receptors, Flt-1 and Flk-1,
      release of cytochrome c from mitochondria, and caspase-3 expression were examined
      in the retinas of 1-day-old rats at 3 hr to 14 days after a hypoxic exposure. The
      mRNA and protein expression of Flt-1 and Flk-1 and the tissue concentration of
      LPO, TNF-alpha, and IL-1beta were upregulated significantly after the hypoxic
      exposure, whereas the content of GSH was decreased significantly. RGC cultures
      also showed increased LPO and decreased GSH levels after hypoxic exposure but
      these effects were reversed in cells treated with melatonin. TNF-alpha and IL
      1beta expression was specifically located on microglial cells, whereas Flt-1 and
      Flk-1 was limited to RGCs as confirmed by double immunofluorescence labeling.
      Cultures of hypoxic microglial cells treated with melatonin showed a significant
      reduction in the release of these cytokines as compared to untreated hypoxic
      cells. Hypoxia induced increase in the cytosolic cytochrome c and caspase-3 in
      RGCs was attenuated with melatonin treatment. The results suggest that, in
      hypoxic injuries, melatonin is neuroprotective to RGCs in the developing retina
      through its antioxidative, anti-inflammatory, and anti-apoptotic effects.
      Melatonin suppressed Flt-1 and Flk-1 expression in retinal blood vessels, which
      may result in reduced retinal vascular permeability and it also preserved
      mitochondrial function as shown by a reduction in cytochrome c leakage into the
      cytosol. The results may have therapeutic implications for the management of
      retinopathy of prematurity.

PMID- 23113622
TI  - Editorial comment to plasmakinetic bipolar versus monopolar transurethral
      resection of non-muscle invasive bladder cancer: a single center randomized
      controlled trial.

PMID- 23113623
TI  - Case report of extended "temporary" use of Levitronix CentriMag right ventricular
      assist device.

PMID- 23113624
TI  - Deceased-donor organ transplantation: knowledge and attitudes among health care
      professionals managing critically ill patients in Karachi.
AB  - OBJECTIVES: Adequate knowledge and positive attitudes of health care
      professionals regarding deceased-donor organ transplants lead to higher donation
      consent rates. This study assessed the knowledge and attitudes of health care
      professionals toward this issue in the light of recent organ transplant
      legislation in Pakistan. MATERIALS AND METHODS: Health care professionals in
      critical care areas of 2 hospitals in Karachi were selected (n=243) and asked to
      complete a questionnaire regarding their knowledge and attitudes toward deceased
      donor organ transplants. RESULTS: In all, 58.8% of the participants were
      physicians and 41.2% were nurses; 91.4% correctly identified brain death; 51.5%
      expressed support for deceased-donor organ transplants; 56.8% had concerns of
      religious rulings against deceased organ donation; 67.5% felt that a government
      body could not run such a system fairly; 56.4% of the respondents would consider
      receiving a deceased-donor organ if needed, but only 35.3% would donate after
      their own death. Only 42.7% and 37% were willing to approach patients and
      families for consent for a deceased-donor organ transplant, respectively. Most of
      those unwilling felt that the patient could refuse, become upset and aggressive,
      and lose trust in the health care professionals. CONCLUSIONS: Before implementing
      a deceased-donor organ transplant system in hospitals, health care professionals
      should attend a training program regarding their concerns. This would increase
      motivation when approaching patients/patients' families for consent, thus
      increasing deceased-donor consent rates.

PMID- 23113625
TI  - Metabolically functional hepatocyte-like cells from human umbilical cord lining
      epithelial cells.
AB  - The primary hepatocyte is the best benchmark for drug biotransformation studies.
      However, due to the severe shortage of primary hepatocytes, there is a need for
      alternative reliable cell source. This study aims to isolate multipotent
      epithelial cells from the umbilical cord, differentiate these cells into
      hepatocyte-like cells (HLCs), and investigate the potential of using the
      differentiated cells for in vitro drug metabolism model. Human umbilical cord
      lining epithelial cells (UCLECs) were subjected to hepatic induction over a
      period of 28 days. HepG2 and cryopreserved human hepatocytes were used as
      control. Immunohistological staining was carried out for alpha-fetoprotein (AFP),
      albumin, cytokeratin 18 (CK18), and 19 (CK19). Glycogen storage ability was
      assessed through periodic acid-Schiff stain. Reverse transcription polymerase
      chain reaction was performed to examine gene expression of hepatic nuclear factor
      4alpha (HNF4alpha) and cytochrome P450 isozymes 1A2, 2C9, 2D6, and 3A4. Ultra
      performance liquid chromatography tandem mass spectrometry (UPLC/MS/MS) was
      utilized to analyze functional metabolic ability of the HLCs, where CYP3A4 was
      chosen as the study focus and testosterone as the drug substrate. After 28 days
      of induction, the fibroblastic phenotype of UCLECs changed to rotund polygonal
      shape resembling that of hepatocytes. Protein expression of AFP and CK19 was
      negative, while albumin and CK18 expression was upregulated. Gene expression of
      HNF4alpha, CYP1A2, CYP2D6, and CYP3A4 was observed but not for CYP2C9. After 4 h
      of incubation with testosterone, UPLC/MS/MS detected 2alpha-, 6beta-, 15beta-,
      and 16beta-hydroxytestosterone. UCLECs are able to differentiate into HLCs that
      express liver-specific markers, and have functional metabolic capabilities.

PMID- 23113626
TI  - The Bandim tuberculosis score: reliability and comparison with the Karnofsky
      performance score.
AB  - BACKGROUND: This study was carried out in Guinea-Bissau's capital Bissau among
      inpatients and outpatients attending for tuberculosis (TB) treatment within the
      study area of the Bandim Health Project, a Health and Demographic Surveillance
      Site. Our aim was to assess the variability between 2 physicians in performing
      the Bandim tuberculosis score (TBscore), a clinical severity score for pulmonary
      TB (PTB), and to compare it to the Karnofsky performance score (KPS). METHOD:
      From December 2008 to July 2009 we assessed the TBscore and the KPS of 100 PTB
      patients at inclusion in the TB cohort and/or at 1 or more follow-up visits; 61
      baseline and 130 follow-up double assessments were obtained. RESULTS: The inter
      observer variability of the TBscore (5 symptoms and 6 clinical findings) varied
      from slight to almost perfect agreement. For the TBscore, all 3 severity classes
      (SC I-III) were observed, while the KPS only yielded 2 of its 3 possible classes.
      The grading of PTB patients into severity classes showed moderate agreement for
      both the TBscore (kappa(w) = 0.52, 95% confidence interval 0.46-0.56) and the KPS
      (kappa(w) = 0.49, 95% confidence interval 0.33-0.65). The intra-class correlation
      coefficient (ICC) was larger for the TBscore than for the KPS (0.822 vs 0.632).
      CONCLUSIONS: The Bandim TBscore had an acceptable inter-observer variability,
      seemed to be more disease-related, and performed better than the KPS.

PMID- 23113627
TI  - Risk evaluation mitigation strategies: the evolution of risk management policy.
AB  - The United States Food and Drug Administration (FDA) has the primary regulatory
      responsibility to ensure that medications are safe and effective both prior to
      drug approval and while the medication is being actively marketed by
      manufacturers. The responsibility for safe medications prior to marketing was
      signed into law in 1938 under the Federal Food, Drug, and Cosmetic Act; however,
      a significant risk management evolution has taken place since 1938. Additional
      federal rules, entitled the Food and Drug Administration Amendments Act, were
      established in 2007 and extended the government's oversight through the addition
      of a Risk Evaluation and Mitigation Strategy (REMS) for certain drugs. REMS is a
      mandated strategy to manage a known or potentially serious risk associated with a
      medication or biological product. Reasons for this extension of oversight were
      driven primarily by the FDA's movement to ensure that patients and providers are
      better informed of drug therapies and their specific benefits and risks prior to
      initiation. This article provides an historical perspective of the evolution of
      medication risk management policy and includes a review of REMS programs, an
      assessment of the positive and negative aspects of REMS, and provides suggestions
      for planning and measuring outcomes. In particular, this publication presents an
      overview of the evolution of the REMS program and its implications.

PMID- 23113628
TI  - Optimal diabetes care outcomes following face-to-face medication therapy
      management services.
AB  - Pharmacists play an integral role in influencing resolution of drug-related
      problems. This study examines the relationship between a pharmacist-led and
      delivered medication therapy management (MTM) program and achievement of Optimal
      Diabetes Care benchmarks. Data within Fairview Pharmacy Services were used to
      identify a group of patients with diabetes who received MTM services during a
      2007 demonstration project (n=121) and a control group who were invited to
      receive MTM services but opted out (n=103). Rates of achieving optimal diabetes
      clinical management for both groups were compared using the D5 diabetes measure
      for years 2006, 2007, and 2008. The D5 components are: glycosolated hemoglobin
      (HbA1c<7%); low-density lipoprotein (<100 mg/dl); blood pressure (<130/80 mmHg);
      tobacco free; and daily aspirin use. Multivariate difference-in-differences (DID)
      estimation was used to determine the impact of 1 year of MTM services on each
      care component. Patients who opted in for MTM had higher Charlson scores, more
      complex medication regimens, and a higher percentage of diabetes with
      complications (P<0.05). In 2007, the percentage of diabetes patients optimally
      managed was significantly higher for MTM patients compared to 2006 values (21.49%
      vs. 45.45%, P<0.01). Nonlinear DID models showed that MTM patients were more
      likely to meet the HbA1c criterion in 2007 (odds ratio: 2.48, 95% confidence
      interval [CI]: 1.04-5.85, P=0.038). Linear DID models for HbA1c showed a mean
      reduction of 0.54% (95% CI: 0.091%-0.98%, P=0.018) for MTM patients. An MTM
      program contributed to improved optimal diabetes management in a population of
      patients with complex diabetes clinical profiles.

PMID- 23113629
TI  - Care Continuum Alliance examines reimbursement and payment models to support
      population health management strategies.

PMID- 23113630
TI  - Effectiveness of interventions in reducing antibiotic use for upper respiratory
      infections in ambulatory care practices.
AB  - The objective was to evaluate the effect of separate interventions on
      antimicrobial prescribing for uncomplicated upper respiratory tract infections.
      The authors conducted a quasi-experimental pre-post study with concurrent control
      groups for each intervention. Academic detailing led to a significant reduction
      in unnecessary antibiotic prescribing. However, there was no significant change
      in antibiotic prescribing in response to educational mailings to providers or to
      provider involvement in patient mailings. Organizations that seek to reduce
      inappropriate use of antibiotics should use proven approaches, even when they are
      more expensive.

PMID- 23113631
TI  - Collaboration across eight research centers: unanticipated benefits and outcomes
      for project managers.
AB  - Managers of transdisciplinary collaborative research lack suitable didactic
      material to support the implementation of research methodologies and to build
      ongoing partnerships with community representatives and peers, both between and
      within multiple academic centers. This article will provide insight on the
      collaborative efforts of project managers involved in multidisciplinary research
      and their subsequent development of a tool kit for research project managers
      and/or directors. Project managers from the 8 Centers for Population Health and
      Health Disparities across the nation participated in monthly teleconferences to
      share experiences and offer advice on how to achieve high participation rates and
      maintain community involvement in collaboration with researchers and community
      leaders to achieve the common goal of decreasing health inequities. In the
      process, managers recognized and seized the opportunity to produce a tool kit
      that was designed for future project managers and directors. Project managers in
      geographically distinct locations maintained a commitment to work together over 4
      years and subsequently built upon an existing communications network to design a
      tool kit that could be disseminated easily to a diverse audience.

PMID- 23113632
TI  - Impact of a chronic disease management program on hospital admissions and
      readmissions in an Australian population with heart disease or diabetes.
AB  - Chronic disease management programs (CDMPs) were introduced in Australia to
      reduce unnecessary health care utilization by the growing population with chronic
      conditions; however, evidence of effectiveness is needed. This study evaluated
      the impact of a comprehensive CDMP, My Health Guardian (MHG), on rate of hospital
      admissions, readmissions, and average length of hospital stay (ALOS) for insured
      individuals with heart disease or diabetes. Primary outcomes were assessed
      through retrospective comparison of members in MHG (treatment; n=5053) to similar
      nonparticipating members (comparison; n=23,077) using a difference-in-differences
      approach with the year before program commencement serving as baseline and the
      subsequent 12 or 18 months serving as the program periods. All outcomes were
      evaluated for the total study population and for disease-matched subgroups (heart
      disease and diabetes). Statistical tests were performed using multivariate
      regression controlling for age, sex, number of chronic diseases, and past
      hospitalization status. After both 12 and 18 months, treatment members displayed
      decreases in admissions (both, P<=0.001) and readmissions (both, P<=0.01), and
      ALOS after 18 months (P<=0.01) versus the comparison group; magnitude of impact
      increased over time for these 3 measures. All outcomes for both disease-matched
      subgroups directionally mirrored the total study group, but the diabetes subgroup
      did not achieve significance for readmissions or ALOS. Within the treatment
      group, admissions decreased with increasing care calls to members (12 and 18
      months, P<0.0001). These results show that MHG successfully reduced the frequency
      and duration of hospital admissions and presents a promising approach to reduce
      the burden associated with hospitalizations in populations with chronic disease.

PMID- 23113633
TI  - Effects of cancer comorbidity on disease management: making the case for diabetes
      education (a report from the SOAR program).
AB  - Individuals with type II diabetes have an increased risk of cancer diagnosis
      (relative risk [RR]=1.12-2.50) and mortality (RR=1.4) compared to normoglycemic
      individuals. Biologic mechanisms, including mitogenic effects of insulin,
      hyperglycemia, and increased oxidative stress, as well as behavioral factors (eg,
      difficulty managing the comorbidity) may explain the elevated risk. To
      investigate the effects of the comorbidity on disease management, the authors
      compared diabetes education utilization in individuals with diabetes-cancer co
      morbidity to utilization by individuals with diabetes in the absence of cancer.
      The effect of diabetes education on outcomes was further assessed in the subset
      of individuals with diabetes-cancer comorbidity. Administrative claims data were
      used for this analysis. The study population included individuals >60 years of
      age and members of both commercial and Medicare Advantage health plans from a
      private national database of payer data, but excluded Medicare fee for service
      and Medicaid patients. Most of these individuals were eligible to receive
      reimbursement for diabetes education. Diabetes education utilization was
      identified using procedure codes. Outcomes were assessed for a 3-year time
      period. There was little difference in diabetes education utilization between
      individuals with diabetes in the absence of cancer (3.8% utilization) and those
      with diabetes-cancer comorbidity (3.5% utilization). Individuals who receive
      diabetes education are more likely to have multiple HbA1c tests per year, fewer
      emergency department visits, fewer hospital admissions, and lower care-associated
      costs (except for outpatient and pharmacy averages). When diabetes coexists with
      cancer, management of diabetes often lags, making diabetes education an
      imperative.

PMID- 23113634
TI  - Economic burden of gouty arthritis attacks for employees with frequent and
      infrequent attacks.
AB  - The objective of this study was to compare episode-related and annual costs and
      work absence days for employees with <3 versus >= 3 annual gout attacks. Human
      Capital Management Services data (2009-2010) from adult employees with gout
      (International Classification of Diseases, Ninth Revision code 274.x) and >= 12
      months of medical and pharmacy benefits were studied. Outcomes of interest
      included medical and drug costs, number of emergency department and urgent care
      visits, number of inpatient days, short- and long-term disability, sick leave,
      workers' compensation costs, and work absence days. An algorithm based on
      diagnosis code and antigout medication use identified acute gout treatment
      episodes. Multivariate analysis compared annual and pre-episode vs. during
      episode outcomes for employees with >= 3 vs. <3 gout annual attacks. Of 3361
      employees with gout, 76 had >= 3 attacks; these employees had higher short-term
      disability costs ($1663 vs. $643, P=0.06) and days (11.68 versus 4.61, P<0.05),
      more emergency room visits (0.55 vs. 0.23, P<0.0001), and urgent care visits
      (0.07 vs. 0.04, P<0.01), and lower pharmacy costs ($1677 vs. $1108, P<0.0001)
      than those with <3 attacks. Medical costs both before ($203 higher) and during
      attacks ($136 higher) were significantly higher for those with >= 3 attacks than
      for those with <3 attacks. Additionally, a quadratic increasing relationship was
      found between number of attacks and cost. Frequency of acute gout attacks (>= 3
      episodes per year) among employees with gout was associated with greater short
      term disability cost, absence days, and emergency department and urgent care
      visits, and trends toward higher overall costs.

PMID- 23113635
TI  - A targeted approach to reducing overutilization: use of percutaneous coronary
      intervention in stable coronary artery disease.
AB  - Overutilization, defined as use of unnecessary care when alternatives may produce
      similar outcomes, results in higher cost without increased value. Overutilization
      can be understood by focusing on settings where overuse is obvious. One example
      is percutaneous coronary intervention (PCI) in chronic stable angina. PCI is a
      potentially lifesaving procedure in an acute setting, but current practice
      guidelines indicate low-risk patients with chronic stable angina should be
      treated initially with optimal medical therapy (OMT) and lifestyle modification.
      A decision to move from this approach to PCI should be based on severity of
      symptoms and degree of risk. Over the last 30 years, advances in equipment,
      adjunctive medical treatments, and safety have made PCI more common. Recent
      evidence questions the benefit of PCI in stable coronary artery disease
      demonstrating no reduction in overall mortality or major cardiac events compared
      to OMT. Despite these findings, some continue to favor aggressive PCI
      interventions over conservative management in low-risk situations. Patients who
      undergo PCI without understanding the evidence may be inappropriately reassured
      that PCI will reduce the need for OMT and the risk of heart attack and death.
      Research shows shared decision-making can result in more conservative care,
      particularly when patients are assessed for health literacy and counseled on
      clinical evidence. Overutilization of PCI can be addressed by promoting active
      participation in an evidence-based decision-making process, allowing the
      opportunity to understand the expected value of invasive procedures over OMT
      alone through processes that encourage physicians to incorporate shared decision
      making prior to PCI in non-acute situations.

PMID- 23113636
TI  - Systematic review of employer-sponsored wellness strategies and their economic
      and health-related outcomes.
AB  - This review determines the characteristics and health-related and economic
      outcomes of employer-sponsored wellness programs and identifies possible reasons
      for their success. PubMed, ABI/Inform, and Business Source Premier databases, and
      Corporate Wellness Magazine were searched. English-language articles published
      from 2005 to 2011 that reported characteristics of employer-sponsored wellness
      programs and their impact on health-related and economic outcomes among US
      employees were accepted. Data were abstracted, synthesized, and interpreted.
      Twenty references were accepted. Wellness interventions were classified into
      health assessments, lifestyle management, and behavioral health. Improved
      economic outcomes were reported (health care costs, return on investment,
      absenteeism, productivity, workers' compensation, utilization) as well as
      decreased health risks. Programs associated with favorable outcomes had several
      characteristics in common. First, the corporate culture encouraged wellness to
      improve employees' lives, not only to reduce costs. Second, employees and
      leadership were strongly motivated to support the wellness programs and to
      improve their health in general. Third, employees were motivated by a
      participation-friendly corporate policy and physical environment. Fourth,
      successful programs adapted to the changing needs of the employees. Fifth,
      community health organizations provided support, education, and treatment. Sixth,
      successful wellness programs utilized technology to facilitate health risk
      assessments and wellness education. Improved health-related and economic outcomes
      were associated with employer-sponsored wellness programs. Companies with
      successful programs tended to include wellness as part of their corporate culture
      and supported employee participation in several key ways.

PMID- 23113637
TI  - Temporal variation in patterns of comorbidities in the medicare population.
AB  - It is widely accepted that Medicare beneficiaries with multiple comorbidities
      (ie, patients with combinations of more than 1 disease) account for a
      disproportionate amount of mortality and expenditures. The authors previously
      studied this phenomenon by analyzing Medicare claims data from 2008 to determine
      the pattern of disease combinations (DCs) for 32,220,634 beneficiaries. Their
      findings indicated that 22% of these individuals mapped to a long-tailed
      distribution of approximately 1 million DCs. The presence of so many DCs, each
      populated by a small number of individuals, raises the possibility that the DC
      distribution varies over time. Measuring this variability is important because it
      indicates the rate at which the health care system must adapt to the needs of new
      patients. This article analyzes Medicare claims data for 3 consecutive calendar
      years, using 2 algorithms based on the Centers for Medicare & Medicaid Services
      (CMS)-Hierarchical Conditions Categories (HCC) claims model. These algorithms
      make different assumptions regarding the degree to which the CMS-HCC model could
      be disaggregated into its underlying International Classification of Diseases,
      Ninth Revision, Clinical Modification codes. The authors find that, although a
      large number of beneficiaries belong to a set of DCs that are nationally stable
      across the 3 study years, the number of DCs in this set is large (in the range of
      several hundred thousand). Furthermore, the small number of beneficiaries
      associated with the larger number of variable DCs (ie, DCs that were not
      constantly populated in all 3 study years) represents a disproportionally high
      level of expenditures and death.

PMID- 23113639
TI  - Dynamics of geminate rebinding of NO with cytochrome c in aqueous solution using
      femtosecond vibrational spectroscopy.
AB  - Using femtosecond vibrational spectroscopy, we investigated the rebinding
      dynamics of NO to cytochrome c (Cytc) and a model heme, microperoxidase-8 (Mp),
      after photodeligation of CytcNO in D(2)O solution and MpNO in an 81%
      glycerol/water (v/v) mixture at room temperature. Whereas the stretching mode of
      the NO band in MpNO was described by a Gaussian centered at 1653 cm(-1) with a
      full width at half-maximum (fwhm) of 41 cm(-1), that in CytcNO revealed an
      asymmetric structured band that peaked at 1619 cm(-1) with an fwhm of about 27
      cm(-1). The structured NO band in CytcNO was well described by the sum of three
      Gaussians, and its shape did not evolve with time but its amplitude decayed
      exponentially with a time constant of 7 +/- 1 ps. The transient NO band in MpNO
      also decayed exponentially with a time constant of 8 +/- 1 ps. Rebinding of NO to
      Cytc was slightly faster than that of NO to Mp and was almost complete by 30 ps,
      which was much faster than the rebinding of NO to myoglobin (Mb). When the
      deligated NO was constrained near the Fe atom either by a viscous solvent or by
      the protein matrix, it rebound to heme Fe much faster than CO, suggesting that NO
      has a higher propensity for binding to heme Fe and the high reactivity governed
      the rebinding kinetics. Moreover, the faster ligand rebinding in Cytc than in Mb
      suggests that Cytc does not have a primary docking site (PDS)-like structure
      found in Mb that suppresses rebinding by restraining ligand motion and the PDS
      can also hold the deligated NO in a manner that impedes NO rebinding; however,
      due to higher NO reactivity with heme Fe, the impediment is not as efficient as
      for CO.

PMID- 23113638
TI  - The DC-HIL ligand syndecan-4 is a negative regulator of T-cell allo-reactivity
      responsible for graft-versus-host disease.
AB  - Acute graft-versus-host disease (GVHD) is the most important cause of mortality
      after allogeneic haematopoietic stem cell transplantation. Allo-reactive T cells
      are the major mediators of GVHD and the process is regulated by positive and
      negative regulators on antigen-presenting cells (APC). Because the significance
      of negative regulators in GVHD pathogenesis is not fully understood, and having
      discovered that syndecan-4 (SD-4) on effector T cells mediates the inhibitory
      function of DC-HIL on APC, we proposed that SD-4 negatively regulates the T-cell
      response to allo-stimulation in acute GVHD, using SD-4 knockout mice. Although
      not different from their wild-type counterparts in responsiveness to anti-CD3
      stimulation, SD-4(-/-)  T cells lost the capacity to mediate the inhibitory
      function of DC-HIL and were hyper-reactive to allogeneic APC. Moreover, infusion
      of SD-4(-/-)  T cells into sub-lethally gamma-irradiated allogeneic mice worsened
      mortality, with hyper-proliferation of infused T cells in recipients. Although
      there my be little or no involvement of regulatory T cells in this model because
      SD-4 deletion had no deleterious effect on T-cell-suppressive activity compared
      with SD-4(+/+)  regulatory T cells. We conclude that SD-4, as the T-cell ligand
      of DC-HIL, is a potent inhibitor of allo-reactive T cells responsible for GVHD
      and a potentially useful target for treating this disease.

PMID- 23113640
TI  - Cobalt electrolyte/dye interactions in dye-sensitized solar cells: a combined
      computational and experimental study.
AB  - We report a combined experimental and computational investigation to understand
      the nature of the interactions between cobalt redox mediators and TiO(2) surfaces
      sensitized by ruthenium and organic dyes, and their impact on the performance of
      the corresponding dye-sensitized solar cells (DSSCs). We focus on different
      ruthenium dyes and fully organic dyes, to understand the dramatic loss of
      efficiency observed for the prototype Ru(II) N719 dye in conjunction with cobalt
      electrolytes. Both N719- and Z907-based DSSCs showed an increased lifetime in
      iodine-based electrolyte compared to the cobalt-based redox shuttle, while the
      organic D21L6 and D25L6 dyes, endowed with long alkoxy chains, show no
      significant change in the electron lifetime regardless of employed electrolyte
      and deliver a high photovoltaic efficiency of 6.5% with a cobalt electrolyte. Ab
      initio molecular dynamics simulations show the formation of a complex between the
      cobalt electrolyte and the surface-adsorbed ruthenium dye, which brings the
      [Co(bpy)(3)](3+) species into contact with the TiO(2) surface. This translates
      into a high probability of intercepting TiO(2)-injected electrons by the oxidized
      [Co(bpy)(3)](3+) species, lying close to the N719-sensitized TiO(2) surface.
      Investigation of the dye regeneration mechanism by the cobalt electrolyte in the
      Marcus theory framework led to substantially different reorganization energies
      for the high-spin (HS) and low-spin (LS) reaction pathways. Our calculated
      reorganization energies for the LS pathways are in excellent agreement with
      recent data for a series of cobalt complexes, lending support to the proposed
      regeneration pathway. Finally, we systematically investigate a series of
      Co(II)/Co(III) complexes to gauge the impact of ligand substitution and of metal
      coordination (tris-bidentate vs bis-tridentate) on the HS/LS energy difference
      and reorganization energies. Our results allow us to trace structure/property
      relations required for further development of cobalt electrolytes for DSSCs.

PMID- 23113642
TI  - Standardization of outcome measures in clinical trials of pharmacological
      treatment for abdominal aortic aneurysm.
AB  - An abdominal aortic aneurysm (AAA) is a common aortic wall disease with an
      increased prevalence in the elderly population (4-8% for those aged >65 years).
      Many AAAs are slow growing and remain insidious. Current standard of care for
      patients with small AAAs (<49 mm) is surveillance, with interventional therapy
      (open surgical repair or endovascular aneurysm repair) recommended for large (>50
      55 mm), rapidly growing (>10 mm/year) or symptomatic AAAs. Although open surgical
      repair or endovascular aneurysm repair are effective, significant short- and long
      term postoperative morbidity and mortality occurs. Currently, there is no
      pharmacological treatment specific for AAA; the need for the development of
      targeted pharmacological therapies based on clinically relevant and feasible
      outcomes acceptable to the medical community, regulatory agencies and third-party
      payers is high. A consensus on such end points will be critical to accelerating
      the development of pharmacological agents to prevent formation, arrest the
      expansion and reduce the rupture risk of AAA.

PMID- 23113641
TI  - Latino youth's internalising behaviours: links to immigrant status and
      neighbourhood characteristics.
AB  - OBJECTIVES: Latinos are the fastest-growing immigrant group in the U.S.A. Yet,
      little is known about the emotional well-being of this population, such as the
      links among family, neighbourhood context and Latino immigrant youth mental
      health. Understanding this link will help determine which contexts negatively
      impact Latino immigrant youth mental health. DESIGN: Drawing data from the
      Project on Human Development in Chicago Neighbourhoods collected in 1994-1995 and
      1997-1999, this study examined links between Latino youth's internalising
      behaviours, based on the Child Behavior Checklist (CBCL), and neighbourhood
      characteristics as a function of immigrant status. The sample included 1040 (aged
      9-17) Latino immigrant youth seen twice over three years and identified as first,
      second or third generation. In this study, neighbourhoods are made up of two to
      three census tracts that reflect similar racial/ethnic and socioeconomic
      composition. Using hierarchical linear regression models, the study also explored
      links between internalising behaviours and neighbourhood characteristics,
      including concentrated disadvantage, immigrant concentration and residential
      stability. RESULTS: First- and second-generation youth had higher internalising
      behaviour scores (i.e., worse mental health) than third-generation youth after
      controlling for youth internalising behaviours at Wave 1, maternal depression and
      family characteristics. First- and second-generation youth were more likely to
      live in high immigrant-concentrated neighbourhoods and first-generation youth
      were more likely to live in residentially unstable neighbourhoods. Controlling
      for neighbourhood clusters eliminated the immigrant-generation internalising
      association. However, second-generation Latino youth living in neighbourhoods
      with higher residential stability had higher levels of internalising behaviour
      problems compared to first- and third-generation youth living in similar
      neighbourhoods. CONCLUSIONS: We found that the interaction between immigrant
      generation and neighbourhood context helps to explain differences observed in the
      mental health of second-generation immigrant youth, a result that may help other
      communities in the USA and other countries better understand the factors that
      contribute to immigrant youth well-being.

PMID- 23113643
TI  - Effect of fermented bilberry extracts on visual outcomes in eyes with myopia: a
      prospective, randomized, placebo-controlled study.
AB  - PURPOSE: To investigate clinically the effects of yeast-fermented bilberry
      extract on visual outcomes in myopic eyes. METHODS: In a prospective, randomized,
      placebo-controlled, cross-over study, we examined 30 eyes of 30 middle-aged
      healthy volunteers (mean age+/-standard deviation, 39.5+/-7.2 years) with myopia
      [manifest spherical equivalent, -2.40+/-1.88 diopters (D)], who were randomly
      assigned to 1 of 2 oral regimens: fermented bilberry extract (400 mg/day) or
      placebo. We quantitatively assessed visual acuity, refraction, pupil constriction
      rate, accommodation, and mesopic contrast sensitivity (CS), before and 1 month
      after treatment. Only the right eyes were tested. The amplitude of accommodation
      and CS were measured with an accommodometer (D'ACOMO; WOC) and a CS unit (VCTS
      6500; Vistech), respectively. From the CS, the area under the log contrast
      sensitivity function (AULCSF) was calculated. RESULTS: The mean amplitude of
      accommodation increased significantly, from 4.62+/-1.88 D before treatment, to
      5.33+/-2.03 D after treatment in the study group (Wilcoxon signed-rank test,
      P=0.002). Moreover, the mesopic AULCSF was significantly increased, from 1.04+/
      0.16 before, to 1.13+/-0.17 after, treatment (P=0.009). However, we found no
      significant changes in accommodation or AULCSF in the control group (P>0.05), or
      any significant changes in any other parameters in either group (P>0.05).
      CONCLUSIONS: The present data show that fermented bilberry extract is effective
      in causing increases in subjective accommodation and in mesopic CS in myopic
      eyes.

PMID- 23113644
TI  - Is combination therapy interferon and ribavirin in patients with chronic
      hepatitis C infection toxic for eyes?
AB  - BACKGROUND: Many side effects of combination therapy using pegylated interferon
      (IFN) and ribavirin for treatment of chronic hepatitis C virus (HCV) infection
      have been well described. Ocular complications are fairly common. Diabetes
      mellitus (DM) and systemic hypertension are possible suggested risk factors for
      development of these complications. PURPOSE: To determine the frequency of
      retinopathy and its risk factors in patients treated with combined pegylated IFN
      and ribavirin for chronic hepatitis C infection. METHODS: Eligible 98 patients
      for HCV treatment with pegylated IFN a-2a, a-2b, and ribavirin between October
      2011 and March 2012 were included. All patients underwent a baseline full
      ophthalmological examination, and any visual complaints during treatment prompted
      a repeat eye examination. RESULTS: Out of the eligible 98 patients, 48 (48.78%)
      patients received pegylated IFN alpha-2a, and the other 50 (51.21%) patients were
      treated with pegylated IFN alpha-2b. Out of 98 patients, 21 (21.42%) had
      diabetes; 19 (19.38%) patients had hypertension and 16 (16.32%) patients had both
      diabetes; and hypertension. Only 8 patients (8.16%) had documented retinopathy [2
      had DM; one had hypertension; 4 had both hypertension and diabetes; and one
      patient without DM or hypertension]. Univariate logistic regression analysis
      revealed that diabetic, hypertensive patients are at increased risk for
      development of IFN-associated retinopathy (IAR) (P=0.007, Odds ratio=6.5, 95%
      confidence interval=1.56-27. CONCLUSION: Retinopathy in chronic HCV-infected
      patients undergoing treatment with combination of pegylated IFN-alpha and
      ribavirin therapy appears to be relatively low, and treatment cessation is rarely
      needed. Diabetic, hypertensive patients are at increased risk for IAR and are
      recommended to be ophthalmologically followed-up.

PMID- 23113645
TI  - Subscleral trabeculectomy with mitomycin-C versus ologen for treatment of
      glaucoma.
AB  - PURPOSE: To compare the results of subscleral trabeculectomy (SST) augmented with
      mitomycin-C (MMC) versus OlogenTM implant regarding intraocular pressure (IOP)
      control and incidence of complications. METHODS: Sixty eyes of 60 patients, who
      planned to undergo SST, were divided into 2 groups. Group I eyes (included thirty
      eyes) were operated upon with SST augmented with intraoperative MMC. Group II
      eyes (included 30 eyes) were operated upon with SST using an Ologen implant. IOP
      and bleb status, as well as reporting postoperative complications, were followed
      up. RESULTS: The follow-up period was 12 months. At 12 months postoperatively,
      the mean IOP was 19.33+/-3.22 mmHg in group I, and 19.87+/-4.17 mmHg in group II,
      with no significant difference between groups. One case in each group had
      hyphema, and 4 cases in group I and 2 cases in group II had shallow anterior
      chamber. One case in group I and no cases in group II had blebitis. There was no
      significant difference regarding the complications between both groups.
      CONCLUSION: We conclude that the use of the Ologen implant in SST is comparable
      to the use of MMC with advantage of avoiding the potential dangerous
      complications related to MMC use in the early (12 months) follow-up period.

PMID- 23113646
TI  - The vitreous humor as a barrier to nanoparticle distribution.
AB  - The vitreous humor represents a significant barrier to the penetration of
      nanoparticulate-based ocular drug delivery systems. The gel structure and
      biochemical components of the vitreous will impact the rate of nanoparticle
      movement through the tissue to reach the retinal tissue. Also the structure of
      the vitreous, flow systems operating within it, age-related structural changes,
      and the presence of inflammation will also have a potential effect on movement.
      To effectively target the posterior retina, the physical properties of the
      nanoparticle formulation are a key element in the design of a system that will
      penetrate through the vitreous barrier.

PMID- 23113647
TI  - Grape seed as a functional food ingredient in bread-making.
AB  - The objective of this study was to determine the effects of grape seed (GS) on
      the rheological and bread-making properties, antioxidant activity and phenolic
      composition of bread. Wheat flour was replaced with GS at levels of 2.5%, 5.0%
      and 7.5%. GS increased the dough development time at a level of 5.0% but did not
      change it at levels of 2.5% and 7.5%. The dough stability value increased from
      6.4 to 12.3 min with the increase of GS content from 0% to 7.5%. Mixing tolerance
      index decreased from 41.1 to 6.4 Brabender Units Equivalent. Extensibility of
      dough containing GS was higher than that of the control dough. The antioxidant
      activities of the bread increased significantly with the increased GS
      substitution. Gallic acid and catechin content increased in the bread containing
      GS. It was concluded that GS could be added to the formulae to improve
      functionality of the bread.

PMID- 23113648
TI  - Atrophic dermatofibrosarcoma protuberans: a case report.

PMID- 23113649
TI  - Brazil nut oil: quality control via triacylglycerol profiles provided by easy
      ambient sonic-spray ionization mass spectrometry.
AB  - Brazil nut oil is one of the important Amazonian natural products in the global
      market. Despite its health benefits and applications in food and cosmetic
      industries, authentication and quality control of the oil are far from
      satisfactory. Several samples of Amazonian Brazil nut oil (authentic oils of
      different geographic origins, commercial oils, and oils adulterated with soybean
      oil) were evaluated by easy ambient sonic-spray ionization mass spectrometry
      (EASI-MS). The samples were characterized on the basis of triacylglycerol
      profiles, and their major ions were subjected to chemometric treatment (principal
      component analysis). The ambient mass spectrometry analysis and the set of major
      ions allowed the characterization of authentic oils, commercial oils, and
      adulterated oils (5% soybean oil) in a few minutes and without sample
      preparation. Therefore, it is shown that quality control of Amazonian vegetable
      oils can be readily accomplished by EASI-MS.

PMID- 23113651
TI  - A new cortical thickness mapping method with application to an in vivo finite
      element model.
AB  - Finite element modelling of musculoskeletal systems, with geometrical structures
      constructed from computed tomography (CT) scans, is a useful and powerful tool
      for biomechanical studies. The use of CT scans from living human subjects,
      however, is still limited. Accurate reconstruction of thin cortical bone
      structures from CT scans of living human subjects is especially problematic, due
      to low CT resolution that results from mandatory low radiation doses and/or
      involuntary movements of the subject. In this study, a new method for mapping
      cortical thickness is described. Using the method, cortical thickness
      measurements of a coxal (pelvis) bone obtained from CT scans of a cadaver were
      mapped to the coxal geometry as obtained through CT scans of a live human
      subject, resulting in accurate cortical thickness while maintaining geometric
      fidelity of the live subject. The mapping procedure includes shape-preserving
      parameterisation, mesh movement and interpolation of thickness using a search
      algorithm. The methodology is applicable to modelling of other bones where
      accurate cortical thickness is needed and for which such data exist. 

PMID- 23113650
TI  - Probing the role of Met221 in the unusual metallo-beta-lactamase GOB-18.
AB  - Metallo-beta-lactamases (MbetaLs) are the main mechanism of bacterial resistance
      against last generation beta-lactam antibiotics such as carbapenems. Most MbetaLs
      display unusual structural features in their active sites, such as binuclear zinc
      centers without carboxylate bridging ligands and/or a Cys ligand in a catalytic
      zinc site. Cys221 is an essential residue for catalysis conserved in B1 and B2
      lactamases, while most B3 enzymes present a Ser in this position. GOB lactamases
      stand as an exception within this picture, with a Met residue in position 221.
      Then, we obtained a series of GOB-18 point mutants in order to analyze the role
      of this unusual Met221 residue. We found that Met221 is essential for the protein
      stability, most likely due to its involvement in a hydrophobic core. In contrast
      to other known MbetaLs, residue 221 is not involved in metal binding or in
      catalysis in GOB enzymes, according to spectroscopic and kinetic studies. Our
      findings show that the essential catalytic features are maintained despite the
      structural heterogeneity among MbetaLs and suggest that a strategy to design
      general inhibitors should be undertaken on the basis of mechanistic rather than
      structural information. 

PMID- 23113652
TI  - Preliminary study of renal hemodynamic alteration in early childhood diabetes
      mellitus.
AB  - Renal hemodynamic study was performed in eight patients associated with type 1,
      early childhood diabetes mellitus (DM) and seven patients associated with type 2,
      early childhood DM. The results in both types of DM revealed a significant
      reduction in peritubular capillary flow and a high value of glomerular filtration
      rate (GFR) in the presence of reduced renal perfusion characteristic of
      glomerular hyperfiltration. These findings imply that renal ischemia has already
      developed in both types of early stage childhood DM and GFR is overestimated in
      DM, which may mislead to improper interpretation of renal function.

PMID- 23113654
TI  - Longitudinal management with crossmatch-compatible platelets for refractory
      patients: alloimmunization, response to transfusion, and clinical outcomes (CME).
AB  - BACKGROUND: The use of crossmatch-compatible platelets (PLTs) improves
      posttransfusion corrected count increments (CCIs) in patients with alloimmune PLT
      refractoriness. However, few reports address the efficacy of utilizing this
      strategy for patients requiring intensive PLT transfusion therapy lasting several
      weeks to months. STUDY DESIGN AND METHODS: Medical records of patients with two
      or more PLT crossmatch assays performed between 2002 and 2010 were reviewed. All
      patients were refractory to random single-donor apheresis PLT units, defined as
      two consecutive 1-hour posttransfusion CCIs of less than 7500. A commercial solid
      phase adherence assay was used for crossmatching. RESULTS: Seventy-one patients
      were included. A median of four crossmatch assays were performed per patient
      (range, 2-17). Mean percent reactivity in initial (58.6%) versus last (55.3%)
      crossmatch assay for each patient demonstrated no trend toward progressive
      alloimmunization (p = NS). A total of 738 crossmatched PLT units were
      administered with a mean +/- standard deviation CCI of 7000 +/- 7900 (n = 443
      units with adequate 1-hr posttransfusion counts), a significant improvement over
      random PLTs (p < 0.001). Patients with an initial crossmatch reactivity of
      greater than 66% were significantly more likely to demonstrate at least one
      panreactive crossmatch assay, impacting the availability of compatible PLTs for
      optimum transfusion support. One patient (1.4%) developed WHO Grade IV bleeding.
      CONCLUSIONS: Progressive alloimmunization to mismatched antigens does not impact
      medium-term transfusion support with crossmatched PLTs. Increased reactivity in
      the initial crossmatch assay can serve as a trigger to initiate workup for HLA
      matched PLTs as a second-line approach. However, for most patients, medium-term
      transfusion support with crossmatched PLTs offers an effective and rapid first
      line approach to management of PLT transfusion refractoriness.

PMID- 23113653
TI  - Discrete frequency infrared microspectroscopy and imaging with a tunable quantum
      cascade laser.
AB  - Fourier-transform infrared (FT-IR) imaging is a well-established modality but
      requires the acquisition of a spectrum over a large bandwidth, even in cases
      where only a few spectral features may be of interest. Discrete frequency
      infrared (DF-IR) methods are now emerging in which a small number of measurements
      may provide all the analytical information needed. The DF-IR approach is enabled
      by the development of new sources integrating frequency selection, in particular
      of tunable, narrow-bandwidth sources with enough power at each wavelength to
      successfully make absorption measurements. Here, we describe a DF-IR imaging
      microscope that uses an external cavity quantum cascade laser (QCL) as a source.
      We present two configurations, one with an uncooled bolometer as a detector and
      another with a liquid nitrogen cooled mercury cadmium telluride (MCT) detector
      and compare their performance to a commercial FT-IR imaging instrument. We
      examine the consequences of the coherent properties of the beam with respect to
      imaging and compare these observations to simulations. Additionally, we
      demonstrate that the use of a tunable laser source represents a distinct
      advantage over broadband sources when using a small aperture (narrower than the
      wavelength of light) to perform high-quality point mapping. The two advances
      highlight the potential application areas for these emerging sources in IR
      microscopy and imaging.

PMID- 23113655
TI  - Biweekly sunitinib regimen reduces toxicity and retains efficacy in metastatic
      renal cell carcinoma: a single-center experience with 31 patients.
AB  - OBJECTIVES: Sunitinib is the standard care for first-line treatment of metastatic
      renal cell carcinoma. The aim of this study was to determine whether a sunitinib
      regimen of 50 mg/day 2-weeks on/1-week off could maintain the same dose-intensity
      as the standard 4-weeks on/2-weeks off schedule, and provide the same efficacy in
      terms of objective response, progression-free survival and overall survival,
      while reducing drug-related toxicity. METHODS: A total of 31 patients with
      metastatic renal cell carcinoma received sunitinib orally at the dose of 50
      mg/day in a 2-weeks on/1-week off regimen until disease progression or
      intolerable toxicities occurred. RESULTS: All enrolled patients were assessable
      in terms of toxicity and response. They received treatment for a median of 16
      months (range 2.0-36.0+ months). A total of 13 patients (42%) obtained an
      objective response; disease stabilization was achieved in 10 patients (32%),
      whereas eight patients (26%) experienced disease progression. The most important
      toxicities were anemia, gastrointestinal effects, fatigue and hypertension, but
      they were all controlled. CONCLUSIONS: Sunitinib 50 mg given orally in a 2-weeks
      on/1-week off regimen can provide a high response rate and avoid drug-related
      toxicities, achieving the same dose intensity as the standard schedule, and
      probably longer disease control.

PMID- 23113656
TI  - Surgical treatment of adult cholesteatoma: long-term follow-up using total
      reconstruction procedure without staging.
AB  - CONCLUSIONS: A total of 330 cases of adult cholesteatoma were operated with canal
      wall down (CWD) and total reconstruction procedure (TRP) without staging.
      Independent of preoperative middle ear conditions, cholesteatoma extent and
      localization, long-term improvement of hearing with a low incidence of residual
      and recurrent disease were achieved. OBJECTIVES: To evaluate long-term surgical
      and hearing results using a well-defined surgical technique without staging in
      adult cholesteatoma. METHODS: The same CWD surgical technique, including
      obliteration of the mastoid cavity, reconstruction of the canal wall, and
      ossiculoplasty with autologous bone, was used by three senior surgeons (1982
      2004). Preoperative and postoperative pure tone average (PTA) for air conduction
      (AC), bone conduction (BC), and air-bone gap (ABG) were assessed and compared 1,
      3, and 6 years after surgery. Various prognostic factors with potential influence
      on long-term hearing outcome were evaluated. RESULTS: Recurrence of AC occurred
      in 10%, residual disease in 3%. Six years after surgery all patients except one
      had a dry ear and over 92% of all cases were water resistant. Three patients
      developed complete deafness. Long-lasting improvement and/or preservation of
      hearing, with maintenance of PTA-ABG closure in 68% of all cases within 20 dB,
      were obtained. Sixty-four (19%) ossicular revisions were performed.

PMID- 23113657
TI  - Antimicrobial susceptibility and combination testing of invasive Stenotrophomonas
      maltophilia isolates.
AB  - BACKGROUND: Treatment of invasive Stenotrophomonas maltophilia infections is
      difficult due to this organism's inherent multidrug resistance and increasing
      resistance to trimethoprim-sulfamethoxazole via acquisition of the sul genes.
      METHODS: In vitro antibiotic susceptibility testing was performed using a
      customized broth microdilution panel. Combination testing for tigecycline with
      anti-Stenotrophomonas agents (i.e. colistin, ticarcillin-clavulanate,
      ceftazidime, and levofloxacin) was done using the cross Etest method. Genotyping
      was done using automated repetitive PCR. RESULTS: A total of 90 patients with
      invasive S. maltophilia infections included: (79%) adults, and 21% children or
      infants [6/12 (50%) cases occurred in infants aged <= 1 year.]. S. maltophilia
      isolates were recovered from blood (69%), lower respiratory (21%) or other sites
      (CSF, peritoneal fluid) (11%). Seventeen percent of the isolates were SXT-R, and
      also demonstrated multi-drug resistant to two or more antibiotic classes.
      Minocycline, tigecycline and colistin had the best in vitro activities. The
      combination testing of tigecycline and colistin gave the best results; 12
      isolates were tested and synergy occurred in 3 isolates while an additional 7
      isolates showed additive results. CONCLUSIONS: We recommend further evaluation
      with killing assays and clinical studies to evaluate the effectiveness of
      tigecycline and colistin combination for invasive S. maltophilia infections.

PMID- 23113658
TI  - CD26-mediated co-stimulation in human CD8(+)  T cells provokes effector function
      via pro-inflammatory cytokine production.
AB  - CD26 is an activation marker of human CD4(+)  T cells, and is associated with T
      cell signal transduction processes as a co-stimulatory molecule. We have
      previously demonstrated that high CD26 cell surface expression on CD4(+)  T cells
      is correlated with the production of T helper type 1 cytokines, whereas CD26(+) 
      T helper cells stimulate antibody synthesis in B cells. Although the cellular and
      molecular mechanisms involved in CD26-mediated CD4(+)  T-cell activation have
      been extensively evaluated by our group and others, the role of CD26 in CD8(+)  T
      cells has not been clearly elucidated. In the present study, we examine the
      effector function of CD8(+)  T cells via CD26-mediated co-stimulation in
      comparison with CD28-mediated co-stimulation. We found that CD26(high)  CD8(+)  T
      cells belong to the early effector memory T-cell subset, and that CD26-mediated
      co-stimulation of CD8(+)  T cells exerts a cytotoxic effect preferentially via
      granzyme B, tumour necrosis factor-alpha, interferon-gamma and Fas ligand. The
      effector function associated with CD26-mediated co-stimulation is enhanced
      compared with that obtained through CD28-mediated co-stimulation, suggesting that
      the CD26 co-stimulation pathway in CD8(+)  T cells is distinct from the CD28 co
      stimulation pathway. Targeting CD26 in CD8(+)  T cells therefore has the
      potential to be useful in studies of immune responses to new vaccine candidates
      as well as innovative therapy for immune-mediated diseases.

PMID- 23113659
TI  - DNA-functionalized gold nanoparticles in macromolecularly crowded polymer
      solutions.
AB  - DNA-functionalized gold nanoparticles (AuNPs) are one of the most commonly used
      reagents in nanobiotechnology. They are important not only for practical
      applications in analytical chemistry and drug delivery, but also for fundamental
      understanding of nanoscience. For biological samples such as blood serum or for
      intracellular applications, the effects of crowded cellular proteins and nucleic
      acids need to be considered. The thermodynamic effect of crowding is to induce
      nanoparticle aggregation. But before such aggregation can take place, there might
      also be a depletion repulsive barrier. Polyethylene glycol (PEG) is one of the
      most frequently used polymers to mimic the crowded cellular environment. We show
      herein that while DNA-functionalized AuNPs are very stable in buffer (e.g., no
      PEG) and citrate-capped AuNPs are very stable in PEG, DNA-functionalized AuNPs
      are unstable in PEG and are easily aggregated. Although such aggregation in PEG
      is mediated by DNA, no sharp melting transition typical for DNA-linked AuNPs is
      observed. We attribute this broad melting to depletion force instead of DNA base
      pairing. The effects of PEG molecular weight, concentration and temperature have
      been studied in detail and we also find an interesting PEG phase separation and
      AuNP partition into the water-rich phase at high temperature.

PMID- 23113660
TI  - The diffusible factor synthase XanB2 is a bifunctional chorismatase that links
      the shikimate pathway to ubiquinone and xanthomonadins biosynthetic pathways.
AB  - The diffusible factor synthase XanB2, originally identified in Xanthomonas
      campestris pv. campestris (Xcc), is highly conserved across a wide range of
      bacterial species, but its substrate and catalytic mechanism have not yet been
      investigated. Here, we show that XanB2 is a unique bifunctional chorismatase that
      hydrolyses chorismate, the end-product of the shikimate pathway, to produce 3
      hydroxybenzoic acid (3-HBA) and 4-HBA. 3-HBA and 4-HBA are respectively
      associated with the yellow pigment xanthomonadin biosynthesis and antioxidant
      activity in Xcc. We further demonstrate that XanB2 is a structurally novel enzyme
      with three putative domains. It catalyses 3-HBA and 4-HBA biosynthesis via a
      unique mechanism with the C-terminal YjgF-like domain conferring activity for 3
      HBA biosynthesis and the N-terminal FGFG motif-containing domain responsible for
      4-HBA biosynthesis. Furthermore, we show that Xcc produces coenzyme Q8 (CoQ8) via
      a new biosynthetic pathway independent of the key chorismate-pyruvate lyase UbiC.
      XanB2 is the alternative source of 4-HBA for CoQ8 biosynthesis. The similar CoQ8
      biosynthetic pathway, xanthomonadin biosynthetic gene cluster and XanB2
      homologues are well conserved in the bacterial species within Xanthomonas,
      Xylella, Xylophilus, Pseudoxanthomonas, Rhodanobacter, Frateuria, Herminiimonas
      and Variovorax, suggesting that XanB2 may be a conserved metabolic link between
      the shikimate pathway, ubiquinone and xanthomonadin biosynthetic pathways in
      diverse bacteria.

PMID- 23113661
TI  - Toward a biosynthetic route to sclareol and amber odorants.
AB  - Ambergris, a waxy substance excreted by the intestinal tract of the sperm whale,
      has been a highly prized fragrance ingredient for millenia. Because of supply
      shortage and price inflation, a number of ambergris substitutes have been
      developed by the fragrance industry. One of the key olfactory components and most
      appreciated substitutes of ambergris, Ambrox is produced industrially by
      semisynthesis from sclareol, a diterpene-diol isolated from Clary sage. In the
      present study, we report the cloning and functional characterization of the
      enzymes responsible for the biosynthesis of sclareol. Furthermore, we
      reconstructed the sclareol biosynthetic pathway in genetically engineered
      Escherichia coli and reached sclareol titers of ~1.5 g/L in high-cell-density
      fermentation. Our work provides a basis for the development of an alternative,
      sustainable, and cost-efficient route to sclareol and other diterpene analogues.

PMID- 23113662
TI  - Reasons for not reporting patient safety incidents in general practice: a
      qualitative study.
AB  - OBJECTIVE: To explore the reasons for not reporting patient safety incidents in
      general practice. DESIGN: Qualitative interviews with general practitioners and
      members of the project group. SETTING: General practice clinics in the Region of
      Northern Jutland in Denmark. SUBJECTS: Twelve general practitioners. MAIN OUTCOME
      MEASURES: The experiences and reflections of the involved professionals with
      regard to system use and non-use. RESULTS: While most respondents were initially
      positive towards the idea of reporting and learning from patient safety
      incidents, they actually reported very few incidents. The major reasons for the
      low reporting rates are found to be a perceived lack of practical usefulness,
      issues of time and effort in a busy clinic with competing priorities, and
      considerations of appropriateness in relation to other professionals. CONCLUSION:
      The results suggest that the visions of formal, comprehensive, and systematic
      reporting of (and learning from) patient safety incidents will be quite difficult
      to realize in general practice. Future studies should investigate how various
      ways of organizing incident reporting at the regional level influence local
      activities of reporting and learning in general practice.

PMID- 23113664
TI  - The MOTIVATE trials: maraviroc therapy in antiretroviral treatment-experienced
      HIV-1-infected patients.
AB  - Although the use of combination antiretroviral therapy has resulted in
      spectacular improvements in morbidity and mortality of HIV-1 infected patients, a
      need for the development of antiretroviral compounds with new mechanisms of
      action remains. Maraviroc (Celsentri((r)); ViiV Healthcare, Middlesex, UK) is the
      only drug of the class of chemokine (C-C motif) receptor 5 antagonists registered
      for treatment for HIV-1-infected antiretroviral therapy-experienced patients.
      Registration was based on the MOTIVATE-1 and -2 studies, which compared the
      efficacy and tolerability of maraviroc in combination with optimized background
      therapy with placebo. The aim of this paper is to review the MOTIVATE studies and
      to discuss issues related to maraviroc therapy in clinical practice such as
      assessment of HIV-1 coreceptor tropism.

PMID- 23113665
TI  - Paying for what was free: lessons from the New York Times paywall.
AB  - In a national online longitudinal survey, participants reported their attitudes
      and behaviors in response to the recently implemented metered paywall by the New
      York Times. Previously free online content now requires a digital subscription to
      access beyond a small free monthly allotment. Participants were surveyed shortly
      after the paywall was announced and again 11 weeks after it was implemented to
      understand how they would react and adapt to this change. Most readers planned
      not to pay and ultimately did not. Instead, they devalued the newspaper, visited
      its Web site less frequently, and used loopholes, particularly those who thought
      the paywall would lead to inequality. Results of an experimental justification
      manipulation revealed that framing the paywall in terms of financial necessity
      moderately increased support and willingness to pay. Framing the paywall in terms
      of a profit motive proved to be a noncompelling justification, sharply decreasing
      both support and willingness to pay. Results suggest that people react negatively
      to paying for previously free content, but change can be facilitated with
      compelling justifications that emphasize fairness.

PMID- 23113663
TI  - Short communication: fasting increases serum concentrations of bilirubin in
      patients receiving atazanavir: results from a pilot study.
AB  - Unconjugated hyperbilirubinemia resulting from therapy with atazanavir is
      physiologically related to hyperbilirubinemia in Gilbert's syndrome (GS). In
      patients with GS, changes in diet have a significant impact on bilirubinemia. Our
      aim was to investigate whether changes in diet affect the level of serum
      bilirubin in patients receiving atazanavir. Thirty patients on stable therapy
      with ritonavir-boosted atazanavir without evidence of GS were enrolled. Hemolysis
      and chronic hepatitis were excluded. After a baseline period of normal intake of
      calories, the patients were randomized to follow a 24-h 400-calorie diet
      (fasting), then a 48-h period of normal calorie intake and, afterward, a 24-h
      period of a high-calorie diet, or the same interventions in inverse order. Serum
      bilirubin concentrations were measured before and after each intervention. A high
      adherence to the recommended diet was observed. The mean unconjugated bilirubin
      concentration before the high-calorie diet was 2.79+/-1.53 mg/dl and after such
      intervention it was 2.70+/-1.40 mg/dl. The mean difference between
      preintervention and postintervention was -0.08+/-0.69 mg/dl (p=NS). The mean
      unconjugated bilirubin concentration before the fasting diet was 2.31+/-1.23
      mg/dl and it was 3.84+/-1.90 mg/dl after. The mean difference between prefasting
      and postfasting was 1.53+/-1.17 mg/dl (p=0.001). According to these results,
      short periods of fasting seem to increase the unconjugated bilirubin
      concentration in patients on atazanavir. A high-calorie diet did not have any
      impact in bilirubin probably because most patients follow similar diets in their
      everyday life.

PMID- 23113666
TI  - First successful combined heart and kidney transplant in Iran: a case report.
AB  - Combined heart and kidney transplant has become an accepted therapy for patients
      with coexisting heart and kidney failure. This method, compared with single-organ
      transplant, has a better outcome. Here, we report the first successful combined
      heart and kidney transplant in Iran. The patient was a 36-year-old man with end
      stage renal disease owing to IgA nephropathy, admitted to Masih Daneshvari
      Hospital in Tehran, Iran for progressive dyspnea and chest pain. In-patient
      evaluations revealed cardiomyopathy leading to end-stage heart failure. Owing to
      concurrent heart and kidney end-stage diseases, combined cardiorenal transplant
      was done. Eight months after his transplant, routine follow-ups have not shown
      any signs of acute rejection. He is now New York Heart Association functional
      class I. Both cardiac and renal functions are within normal ranges. Good outcome
      during follow-up for this case justifies simultaneous heart plus kidney
      transplants as an alternate treatment for patients with advanced disease of both
      organs. 

PMID- 23113667
TI  - Self-transcendence, nurse-patient interaction and the outcome of multidimensional
      well-being in cognitively intact nursing home patients.
AB  - AIMS AND OBJECTIVES: The aim of this study was to investigate the associations
      between age, gender, self-transcendence, nurse-patient interaction and
      multidimensional well-being as the outcome among cognitively intact nursing home
      patients. BACKGROUND: Self-transcendence is considered to be a vital resource of
      well-being in vulnerable populations and at the end of life. Moreover, the
      quality of care and the nurse-patient interaction is found to influence self
      transcendence and well-being in nursing home patients. DESIGN AND METHOD: A cross
      sectional design employing the Self-Transcendence Scale, the Nurse-Patient
      Interaction Scale, the FACT-G Quality of Life and the FACIT-Sp Spiritual Well
      Being questionnaires was adopted. A sample of 202 cognitively intact nursing home
      patients from 44 nursing homes in central Norway was selected. A previous
      documented two-factor construct of self-transcendence was applied. The
      statistical analyses were carried out by means of independent sample t-test,
      correlation and regression analyses. RESULTS: Multiple linear regression analyses
      revealed significant relationships between interpersonal self-transcendence and
      social, functional and spiritual well-being, whereas intrapersonal self
      transcendence significantly related to emotional, social, functional and
      spiritual well-being. Nurse-patient interaction related to physical, emotional
      and functional well-being. Age and gender were not significant predictors for
      well-being, except for functional and spiritual well-being where women scored
      higher than men. CONCLUSION: Nurse-patient interaction and self-transcendence are
      vital resources for promoting well-being physically, emotionally, functionally,
      socially and spiritually among cognitively intact nursing home patients.
      RELEVANCE TO CLINICAL PRACTICE: Nurse-patient interaction signifies vital and
      ultimate nursing qualities promoting self-transcendence and multidimensional well
      being. These findings are important for clinical nursing intending to increase
      patients' well-being.

PMID- 23113668
TI  - Computer modelling of maximal displacement forces in endoluminal thoracic aortic
      stent graft.
AB  - The objective of this study was to determine the orientation and magnitude of
      maximal displacement forces (DFs) in the thoracic aortic aneurysm endograft (TAA
      endograft) in three-dimensional (3D) space. Theoretical computer model
      representing the anatomically worst-case scenario with respect to DF magnitude
      was used to calculate the magnitude and orientation of maximal DF. A patient
      specific anatomical computer model of typically seen, average size anatomy was
      used to analyse the progression of DF throughout the cardiac cycle. Maximal DFs
      were 35.01 and 37.32 N in standing and supine position, respectively, in 46-mm
      diameter TAA graft with 90 degrees  bend. A patient-specific model shows that a
      maximal DF magnitude is achieved at the peak systolic flow. In both models, the
      orientation of the DF vector was perpendicular to the greater curvature of the
      aorta, with upward (cranial) and sideways components. The effect of shearing
      force on the total DF that acts on the TAA endograft was found negligible due to
      the several orders of magnitude stronger contribution of pressure forces to the
      total DF relative to the wall shear stress contribution, resulting in aortic
      diameters and angulation being the main drivers of DF. It was discovered that the
      TAA endografts can be subjected to much stronger DF than previously suspected.
      The magnitude of maximal DF in thoracic aorta in the worst-case scenario could be
      as high as 35.01 N (standing) and 37.32 N (supine). This new information should
      be used in the process of designing new generations of TAA endografts with better
      migration resistance properties. 

PMID- 23113669
TI  - Markers of systemic inflammation in delayed pressure urticaria.
AB  - BACKGROUND: We have previously reported, increased plasma IL-6 concentration in
      chronic urticaria. In addition, it has been suggested that IL-6 and C-reactive
      protein (CRP) may be useful markers of the disease activity. AIM: The aim of this
      study was to evaluate whether a systemic inflammation is present in delayed
      pressure urticaria (DPU). METHODS: Plasma IL-6 and serum CRP concentrations,
      biomarkers of acute phase response, were measured in DPU, and the healthy
      subjects matched by age, gender, and BMI using ELISA method. RESULTS: DPU
      patients showed significantly higher plasma IL-6 and serum CRP concentrations
      than the healthy subjects. CONCLUSIONS: Similarly to the known locally increased
      IL-6 activity in DPU lesions, the elevated circulating levels of IL-6 and CRP
      have been currently found in DPU. This indicates that the disease induces a
      systemic inflammatory process, termed the acute phase response.

PMID- 23113670
TI  - Colorimetric paper bioassay for the detection of phenolic compounds.
AB  - A new type of paper based bioassay for the colorimetric detection of phenolic
      compounds including phenol, bisphenol A, catechol and cresols is reported. The
      sensor is based on a layer-by-layer (LbL) assembly approach formed by
      alternatively depositing layers of chitosan and alginate polyelectrolytes onto
      filter paper and physically entrapping the tyrosinase enzyme in between these
      layers. The sensor response is quantified as a color change resulting from the
      specific binding of the enzymatically generated quinone to the multilayers of
      immobilized chitosan on the paper. The color change can be quantified with the
      naked eye but a digitalized picture can also be used to provide more sensitive
      comparison to a calibrated color scheme. The sensor was optimized with respect to
      the number of layers, pH, enzyme, chitosan and alginate amounts. The colorimetric
      response was concentration dependent, with a detection limit of 0.86 (+/-0.1)
      MUg/L for each of the phenolic compounds tested. The response time required for
      the sensor to reach steady-state color varied between 6 and 17 min depending on
      the phenolic substrate. The sensor showed excellent storage stability at room
      temperature for several months (92% residual activity after 260 days storage) and
      demonstrated good functionality in real environmental samples. A procedure to
      mass-produce the bioactive sensors by inkjet printing the LbL layers of
      polyelectrolyte and enzyme on paper is demonstrated.

PMID- 23113671
TI  - Spindle cell rhabdomyosarcoma of the neck with t(6;8) translocation: report of a
      case and literature review.
AB  - Spindle cell rhabdomyosarcoma is an uncommon subtype of embryonal
      rhabdomyosarcoma. Found almost exclusively in children, these tumors are
      classically located in the paratesticular and head and neck regions.
      Morphologically these lesions can resemble several other benign or malignant soft
      tissue spindle cell lesions, especially smooth muscle or myofibroblastic tumors,
      and thus immunohistochemical staining is often needed to prove skeletal muscle
      differentiation. Although there is extensive literature reporting the genetics of
      embryonal rhabdomyosarcoma, little is reported specific to the spindle cell
      subtype. Below we present the case of a 7-month-old male presenting with a large
      posterior neck mass that was diagnosed as spindle cell rhabdomyosarcoma.
      Karyotype evaluation revealed a t(6;8) (p12;q11.2) chromosomal translocation
      within the lesion. We review the histologic and immunohistochemical diagnosis of
      these tumors and discuss the genetics of rhabdomyoscarcomas.

PMID- 23113672
TI  - Infectious encephalitis: a description of a Norwegian cohort.
AB  - BACKGROUND: Prompt recognition and rapid initiation of adequate treatment are
      important for the outcome of encephalitis. Despite extensive diagnostic testing,
      the causative agent often remains unknown. The aim of this study was to
      investigate in how many patients the causative agent was found. METHODS: Adults
      (>= 18 y) diagnosed with ICD codes indicating encephalitis between 2000 and 2009
      at Oslo University Hospital, Ulleval were retrospectively studied. Causative
      agents, clinical presentation, and demographic characteristics were registered.
      Those with an identified causative agent were compared to those for whom no agent
      could be found. RESULTS: Of 136 registered patients, 70 were included in the
      study. Sixty-six did not fulfil our inclusion criteria or were diagnosed with
      other, more probable conditions. The causative agent was found in 30/70 (43%)
      patients; herpes simplex type 1 (10/70, 14%) and varicella zoster virus (6/70,
      9%) were the most frequently identified agents. A bacterial cause was found in
      6/70 (9%). Patients with an identified agent were more often men and had been ill
      longer than those for whom no agent could be found. Computed tomography and
      magnetic resonance imaging were more likely to be abnormal in those patients
      where a causative agent was found. Five of the 70 (7%) patients died of the
      infection. The identification rate did not increase during the study period.
      CONCLUSIONS: The diagnosis of encephalitis remains a challenge, and in many
      patients no causative agent is found. Clinically, immune-mediated encephalitis
      cannot be differentiated from infectious encephalitis and represents an important
      differential diagnosis. More knowledge is needed to improve our diagnostic
      skills.

PMID- 23113673
TI  - Evaluation of solution-processable carbon-based electrodes for all-carbon solar
      cells.
AB  - Carbon allotropes possess unique and interesting physical, chemical, and
      electronic properties that make them attractive for next-generation electronic
      devices and solar cells. In this report, we describe our efforts into the
      fabrication of the first reported all-carbon solar cell in which all components
      (the anode, active layer, and cathode) are carbon based. First, we evaluate the
      active layer, on standard electrodes, which is composed of a bilayer of polymer
      sorted semiconducting single-walled carbon nanotubes and C(60). This carbon-based
      active layer with a standard indium tin oxide anode and metallic cathode has a
      maximum power conversion efficiency of 0.46% under AM1.5 Sun illumination. Next,
      we describe our efforts in replacing the electrodes with carbon-based electrodes,
      to demonstrate the first all-carbon solar cell, and discuss the remaining
      challenges associated with this process.

PMID- 23113674
TI  - Neutrophil to lymphocyte ratio in evaluation of inflammation in patients with
      chronic kidney disease.
AB  - AIM: The current data have proven the pivotal role of inflammation in the
      development of atherosclerosis and cardiovascular diseases in patients with
      chronic kidney disease (CKD). Neutrophil to lymphocyte (N/L) ratio has
      increasingly been reported as a measure of systemic inflammation. This study
      assessed N/L ratio and investigated its associations with standard inflammatory
      biomarkers in different stages of CKD patients. MATERIAL AND METHODS: This cross
      sectional study included 30 predialysis, 40 hemodialysis, 35 peritoneal dialysis
      patients, and 30 healthy subjects. N/L ratio and important clinical and
      laboratory parameters were registered. Multivariate regression analyses were
      carried out to investigate the relations of N/L ratio. RESULTS: N/L ratio was
      significantly higher in each patient group compared to the healthy subjects (for
      all, p < 0.001). It was positively correlated with interleukin-6 (IL-6) (r =
      0.393, p < 0.001) and high-sensitivity C-reactive protein (hs-CRP) (r = 0.264, p
      = 0.002) levels and negatively correlated with hemoglobin (r = -0.271, p =
      0.001), serum albumin (r = -0.400, p < 0.001), and high-density lipoprotein (HDL)
      cholesterol levels (r = -0.302, p < 0.001). In CKD patients with hypertension
      (HT), higher N/L ratio was detected when compared to those without HT (p =
      0.006). Having CKD, the presence of HT, serum albumin, HDL-cholesterol, IL-6, and
      hs-CRP levels were found to be independent predictors of the ratio after
      adjusting for significant covariates (p < 0.001). CONCLUSION: An easy and
      inexpensive laboratory measure of N/L ratio might provide significant information
      regarding inflammation in CKD including predialysis and dialysis patients.

PMID- 23113675
TI  - Therapeutic drug monitoring of imatinib in chronic myeloid leukemia: experience
      from 1216 patients at a centralized laboratory.
AB  - This study set out to examine in a large real-life cohort of patients with
      chronic myeloid leukemia (CML) the impact of imatinib threshold of 1000 ng/mL on
      molecular response, as suggested in a small subset of patients. Patient plasma
      samples were submitted from around France to a central facility, free of charge
      under the auspices of the European Treatment and Outcome Study (EUTOS) for CML.
      Submitting physicians were required to complete an 'imatinib monitoring request
      form', including details of why therapeutic drug monitoring (TDM) was requested,
      dose and duration of imatinib treatment, cytogenetic and molecular response,
      adverse events, and concurrent medications. Imatinib trough plasma concentration
      (C(min)) was measured at the central facility. Among 1985 eligible plasma samples
      analyzed, from 1216 CML patients, imatinib C(min) correlated positively with
      reported imatinib dose, but interpatient variability in C(min) was high (60%). A
      logistic regression analysis revealed that treatment duration and imatinib C(min)
      > 1000 ng/mL were significantly associated with major and complete molecular
      responses with odds ratios of 1.69 and 2.08, respectively. These data support in
      real-life setting that imatinib C(min) threshold of 1000 ng/mL is associated with
      major and complete molecular response and that TDM could play an important role
      in dose optimization.

PMID- 23113676
TI  - The residual risk of transfusion-related acute lung injury at the American Red
      Cross (2008-2011): limitations of a predominantly male-donor plasma mitigation
      strategy.
AB  - BACKGROUND: The American Red Cross began preferentially distributing plasma from
      male donors in 2007 and subsequently observed an 80% decrease in reported cases
      of transfusion-related acute lung injury (TRALI) after plasma transfusion. Plasma
      distributions from male donors now exceed 99% for groups A, B, and O, but only
      approximately 60% for group AB. We evaluated the ongoing risk of TRALI and the
      ABO blood group of involved plasma donors. STUDY DESIGN AND METHODS: The rate of
      suspected TRALI per distributed components before (2006) and after (2008-2011)
      implementing the predominantly male-donor plasma strategy is compared. RESULTS:
      The risk of TRALI from the general inventory of distributed plasma decreased
      significantly from 18.6 cases per million units in 2006 to 4.2 cases per million
      units in 2008 to 2011 (p < 0.0001). However, the risk from AB plasma did not
      change (26.3 cases per million units) and was significantly greater than group A,
      B, and O plasma in 2008 to 2011 (1.8 per million units; odds ratio 14.5; 95%
      confidence interval, 6.8-30.9). Group AB plasma from female donors with HLA or
      HNA antibodies accounted for 14 of 28 (50%) of TRALI cases but less than 4% of
      all plasma units distributed in 2008 to 2011. CONCLUSION: The risk of TRALI after
      plasma transfusion has been markedly reduced for blood groups A, B, and O but not
      for AB, reflecting continued reliance on group AB plasma from female donors to
      meet increasing demand.

PMID- 23113677
TI  - Potential tumor markers of renal cell carcinoma: alpha-enolase for postoperative
      follow up, and galectin-1 and galectin-3 for primary detection.
AB  - The diagnosis of renal cell carcinoma is currently based on imaging techniques,
      mainly because there is no blood marker available for its detection. Thus, there
      is still the need for the development of novel tumor markers. We examined plasma
      levels of eight proteins in 15 renal cell carcinoma patients before and after
      surgery, and in 51 healthy controls using enzyme-linked immunosorbent assay.
      Plasma levels of alpha-enolase, calnexin, galectin-1, galectin-3 and lectin
      mannose-binding 2 were significantly higher in renal cell carcinoma patients than
      in controls (P < 0.05). Among these proteins, the sensitivities for galectin-1
      and galectin-3 were higher than those for calnexin and lectin mannose-binding 2
      in the specificity range from 80% to 100%. A combined use of galectin-1 and
      galectin-3 showed 98% specificity and 47% sensitivity. In addition, the assays
      showed that plasma alpha-enolase levels decreased significantly 4 weeks after
      nephrectomy (P = 0.0034), and this tendency continued until 12 weeks after
      nephrectomy (P = 0.0156). These findings suggest that alpha-enolase could be used
      in the postoperative follow up of renal cell carcinoma patients, whereas the
      combined use of galectin-1 and galectin-3 might represent a useful tool for
      primary detection.

PMID- 23113678
TI  - The effect of intravenous lidocaine infusion on bronchoalveolar lavage cytology
      in equine recurrent airway obstruction.
AB  - BACKGROUND: Lidocaine decreases neutrophilic inflammation in models of acute lung
      injury and decreases inflammation in asthmatic patients. Neutrophilic
      bronchiolitis develops in recurrent airway obstruction (RAO), but it remains
      unknown if lidocaine infusion decreases neutrophil migration into the airways.
      HYPOTHESIS: Lidocaine decreases neutrophilic inflammation as measured in BALF in
      RAO-affected horses. ANIMALS: Six RAO-susceptible horses in remission. METHODS:
      In a randomized cross-over design, horses received lactated Ringer's solution
      (LRS) IV or lidocaine hydrochloride IV with a minimum of 4 weeks at pasture
      between treatments. Treatments were delivered as continuous infusions beginning 4
      hours before and for 68 hours during exposure to hay and straw challenge.
      Clinical score (CS, grade 0-8), maximal change in pleural pressure (?Ppl(max) ),
      and bronchoalveolar lavage fluid (BALF) cytology were measured at baseline and
      the end of challenge (day 4). Plasma lidocaine concentrations were monitored
      daily. RESULTS: At baseline, there were no significant differences in variables
      between treatments. Plasma lidocaine concentration was consistently > 1100 ng/mL.
      After challenge, CS increased significantly [baseline: 2/8 (2-3), [median
      (interquartile range)]; day 4: 4/8 (4-5) P = .0006] as did ?Ppl(max) [baseline:
      3.6 (2.63-4.95) cmH(2) 0; day 4: 9.62 (6.5-16) P = .0036], but there was no
      difference between treatments. Percentage of neutrophils was not different
      between treatments, but lidocaine infusion significantly increased BALF total
      cells [baseline: LRS 2.18 +/- 0.82 * 10(5) cells/mL (mean +/- SD), lidocaine 1.6
      +/- 0.3 * 10(5) , day 4: LRS 2.0 +/- 0.88 * 10(5) , lidocaine 4.4 +/- 2 * 10(5)
      (P = .0045)]. CONCLUSIONS AND CLINICAL IMPORTANCE: Lidocaine does not decrease
      neutrophilic inflammation in RAO.

PMID- 23113679
TI  - CsCoO(2) featuring a novel polyoxocobaltate(III) anion based on a two-dimensional
      architecture of interconnected tetrahedra.
AB  - CsCoO2 has been prepared along the azide/nitrate route as a reddish black
      microcrystalline powder at 833 K. According to single crystal X-ray analysis, the
      title compound crystallizes as a structure type novel for oxides (Cmca,Z = 8, a =
      5.9841(1) A, b = 12.2458(2) A, c = 8.2650(1) A). The prominent features of the
      structure are pairs of edge-linked CoO4 tetrahedra to form Co2O6 dimers, which
      are condensed by vertex sharing of the four remaining unshared oxygen atoms to
      form a two-dimensional architecture of a puckered polyoxyanion spreading along
      (010). Upon cooling, CsCoO2 undergoes a virtually second order phase transition
      at ~100 K leading to a systematic dovetail twin (C2/c). The magnetic
      susceptibilities show the dominance of antiferromagnetic interactions with a
      remarkably high Neel temperature of 430 K indicating a very strong
      antiferromagnetic superexchange between the Co(3+) ions. The spin-exchange for
      CsCoO2 can be addressed as a set of strongly antiferromagnetically coupled quasi
      one-dimensional chains, which are weakly coupled to neighboring chains by
      ferromagnetic interaction. 

PMID- 23113680
TI  - Tigecycline in carbapenem-resistant Acinetobacter baumannii bacteraemia:
      susceptibility and clinical outcome.
AB  - Although tigecycline is considered one of the few therapeutic options for
      carbapenem-resistant Acinetobacter baumannii (CRAB) bacteraemia, its role in the
      treatment of CRAB bacteraemia remains unclear. We describe the clinical outcomes
      of 9 patients who received tigecycline for CRAB bacteraemia. Although all CRAB
      blood isolates were susceptible to tigecycline, 5 (56%) deaths were related to
      CRAB bacteraemia and 1 case of breakthrough CRAB bacteraemia was observed during
      tigecycline therapy. Clinical outcomes of tigecycline therapy may be poor in
      patients with tigecycline-susceptible CRAB bacteraemia, although multiple factors
      including delayed treatment could contribute to the poor outcomes.

PMID- 23113681
TI  - Clinical and analytical evaluation of an immunoturbidimetric heart-type fatty
      acid-binding protein assay.
AB  - BACKGROUND: Heart-type fatty acid-binding protein (H-FABP) is a low molecular
      weight protein involved in the intracellular uptake and buffering of long chain
      fatty acids in the myocardium. It is an early marker for ACS. We have evaluated
      the Randox Laboratories immunoturbidimetric assay on a Siemens Advia 1800
      analyzer. The assay employs latex particles coated with mouse monoclonal anti
      HFABP antibodies to generate turbidity. METHODS: We used redundant patient
      samples and pools to assess precision, functional sensitivity, limit of
      detection, linearity, recovery of recombinant H-FABP and interference. We
      evaluated the 99th centile values and compared H-FABP with troponin in samples
      routinely received from chest pain patient samples. RESULTS: Precision was
      typically < 10% and 12.5% at all concentrations for within and between batches.
      The functional sensitivity was 2.4 MUg/L. The assay was linear on dilution over
      the range 2.76-115 MUg/L. Recovery of recombinant H-FABP was approximately 20
      25%. No interference was seen with haemoglobin concentrations <1.5 g/L, bilirubin
      < 250 MUg/L and triacylglycerol < 5 mmol/L or rheumatoid factor. The 99th centile
      value in a reference population with eGFR > 60mL/min/1.73m(2) was 9.1 MUg/L with
      no significant gender difference. H-FABP was measured in routine clinical samples
      (N = 1310) received for troponin I measurement. Using Siemens TnI > 50 ng/L as an
      indicator of myocardial damage, the ROC area under curve for H-FABP was 0.82.
      CONCLUSIONS: The immunoturbidimetric H-FABP assay is robustly designed and shows
      good analytical performance. It is therefore well suited for use in a routine
      clinical laboratory.

PMID- 23113682
TI  - Water dynamics in divalent and monovalent concentrated salt solutions.
AB  - Water hydrogen bond dynamics in concentrated salt solutions are studied using
      polarization-selective IR pump-probe spectroscopy and 2D IR vibrational echo
      spectroscopy performed on the OD hydroxyl stretching mode of dilute HOD in
      H(2)O/salt solutions. The OD stretch is studied to eliminate vibrational
      excitation transfer, which interferes with the dynamical measurements. Though
      previous research suggested that only the anion affected dynamics in solution,
      here it is shown that the cation plays a role as well. From FT-IR spectra of the
      OD stretch, it is seen that replacing either ion of the salt pair causes a shift
      in absorption frequency relative to that of the OD stretch absorption in bulk
      pure water. This shift becomes pronounced with larger, more polarizable anions or
      smaller, high charge-density cations. The vibrational lifetime of the OD hydroxyl
      stretch in these solutions is a local property and is primarily dependent on the
      nature of the anion and whether the OD is hydrogen bonded to the anion or to the
      oxygen of another water molecule. However, the cation still has a small effect.
      Time dependent anisotropy measurements show that reorientation dynamics in these
      concentrated solutions is a highly concerted process. While the lifetime, a local
      probe, displays an ion-associated and a bulk-like component in concentrated
      solutions, the orientational relaxation does not have two subensemble dynamics,
      as demonstrated by the lack of a wavelength dependence. The orientational
      relaxation of the single ensemble is dependent on the identity of both the cation
      and anion. The 2D IR vibrational echo experiments measure spectral diffusion that
      is caused by structural evolution of the system. The vibrational echo
      measurements yield the frequency-frequency correlation function (FFCF). The
      results also show that the structural dynamics are dependent on the cation as
      well as the anion.

PMID- 23113683
TI  - Effects of oat beta-glucan and barley beta-glucan on fecal characteristics,
      intestinal microflora, and intestinal bacterial metabolites in rats.
AB  - The primary objective was to determine the beneficial effects of oat beta-glucan
      (OG) and barley beta-glucan (BG) on gut health. A total of 200 male Sprague
      Dawley rats were divided into 5 groups of 40 rats each, control group (CON), low
      dose OG-administered group (OGL), high-dose OG-administered group (OGH), low-dose
      BG-administered group (BGL), and high-dose BG-administered group (BGH). OGL and
      OGH were administered oat beta-glucan by intragastric gavage at a dose of 0.35
      g/kg of body weight (BW) and 0.70 g/kg of BW daily for 6 weeks, and BGL and BGH
      were administered barley beta-glucan. The CON received normal saline. Intestinal
      health-related indexes were analyzed at baseline, week 3, week 6, and week 7.
      Cereal beta-glucan significantly influenced the fecal water content, pH value,
      ammonia levels, beta-glucuronidase activity, azoreductase activity, and colonic
      short-chain fatty acid (SCFA) concentrations (p < 0.05). Moreover, the population
      of  Lactobacillus  and  Bifidobacterium  increased (p < 0.05), whereas the number
      of  Enterobacteriaceae  decreased (p < 0.05) in a dose-dependent manner during
      the period of cereal beta-glucan administration. These results suggested that
      cereal beta-glucan might exert favorable effects on improving intestinal
      functions and health but the gut-health-promoting effects of oat beta-glucan were
      better than those of barley beta-glucan.

PMID- 23113684
TI  - Angiopoietins as biomarker of disease activity and response to therapy in
      multiple myeloma.
AB  - Tumor angiogenesis is a complex process involving interplay of several angiogenic
      regulators. In the present study, mRNA expression and circulating levels of
      vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF),
      angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), hypoxia inducible factor (HiF)
      1alpha, circulating endothelial progenitor cells (cEPCs) and bone marrow
      microvessel density (MVD) were evaluated in multiple myeloma (MM). Compared to
      healthy controls, the levels of VEGF, bFGF, Ang-2, HiF-1alpha and cEPCs were
      significantly higher and Ang-1 and Ang-1/Ang-2 were lower in MM (p < 0.01). cEPC
      numbers correlated with Ang-1 (p = 0.03), Ang-2 (p = 0.01) and VEGF (p = 0.002).
      On multivariate analysis, reduced Ang-1/Ang-2 ratio (p = 0.005) at baseline was
      an independent predictor for response to therapy. After therapy, a decrease in
      Ang-2 (p < 0.001) and an increase in Ang-1/Ang-2 ratio (p = 0.003) were observed
      in responders. This study highlights the role of angiopoietins in MM which may,
      thus, be evaluated as potential targets for anti-angiogenic therapy in future.

PMID- 23113685
TI  - Current and emerging new treatment strategies for mantle cell lymphoma.
AB  - Mantle cell lymphoma is a relatively rare type of non-Hodgkin lymphoma that
      accounts for approximately 6000 new cases per year in the USA. The median age of
      patients at presentation is around 65 years, and almost all patients present with
      stage IV disease. Over the past decade, our understanding of the molecular
      pathology of the disease has substantially improved. Furthermore, intensive
      chemotherapy treatment options were developed to improve the complete remission
      rates and to prolong the remission duration. More recently, several targeted
      agents have shown promising clinical results with good safety profiles. Future
      directions should focus on incorporating these novel agents in new less toxic
      regimens, and should also identify biomarkers that can better match patients with
      effective treatment strategies.

PMID- 23113686
TI  - Treatment of invasive candidiasis in neutropenic patients: systematic review of
      randomized controlled treatment trials.
AB  - Candidemia and invasive candidiasis (CIC) is associated with considerable
      morbidity and mortality, with a paucity of controlled data in neutropenic
      patients. A systematic review was conducted of available data for the treatment
      of CIC during neutropenia. A structured OVID search of multiple databases was
      performed. Data from randomized controlled trials of CIC and of empirical
      antifungal therapy in febrile neutropenic patients was included. A total of 17
      trials randomizing 342 neutropenic patients were included. Eight of the studies
      compared amphotericin B (AmB) to other non-polyene antifungal agents. Pooling of
      results favored use of comparator compounds (odds ratio [OR] 0.73; 95% confidence
      interval [CI] 0.42-1.29). To strengthen our analysis, a pre-planned sensitivity
      analysis was also conducted. Overall, there was a non-significant benefit in
      favor of non-polyene compounds. Across studies, echinocandins provided the
      benefit of favorable outcomes with fewest side effects and toxicity.

PMID- 23113688
TI  - Comparison of 6-hydroxydopamine lesions of the substantia nigra and the medial
      forebrain bundle on a lateralised choice reaction time task in mice.
AB  - Parkinson's disease is most commonly modelled via unilateral infusion of the
      neurotoxin 6-hydroxydopamine (6-OHDA) in the rat, but recent work has been aimed
      to translate the reproducibility and reliability of the model to the mouse. Here
      we present the effects of unilateral 6-OHDA lesions to either the medial
      forebrain bundle or the substantia nigra (SN) in mice, which were trained on a
      lateralised choice reaction time (RT) task. This task measures response accuracy
      as well as RT and movement time latencies, and offers the opportunity for a more
      fine-grained analysis of the precise nature of the movement deficit, motor
      learning and functional recovery than can be achieved using classical tests of
      simple motor asymmetry. Both lesion types caused impaired response accuracy,
      which was more pronounced when responses had to be directed contralateral to the
      lesion. Furthermore, movement times were increased for both lesion groups,
      whereas only the bundle lesion group displayed a RT deficit. The lesions were
      stable over three consecutive weeks of testing, therefore lesion-type and
      behavioural assessment on the operant task are suitable to investigate the
      dopaminergic system in parkinsonian mice. Both lesions were stable over time, and
      were more pronounced when responses were directed in contralateral space; the
      mice with more complete bundle lesions displayed a greater deficit than mice that
      received lesions to the SN. The translation of this choice RT task will be
      beneficial for the assessment of therapeutics in mouse models of the disease.

PMID- 23113687
TI  - HLA-DM: arbiter conformationis.
AB  - The recognition by CD4(+) T cells of peptides bound to class II MHC (MHCII)
      molecules expressed on the surface of antigen-presenting cells is a key step in
      the initiation of an adaptive immune response. Presentation of peptides is the
      outcome of an intracellular selection process occurring in dedicated endosomal
      compartments involving, among others, an MHCII-like molecule named HLA-DM (DM).
      The impact of DM on the epitope selection machinery has been known for more than
      15 years. However, the mechanism by which DM skews the presented repertoire in
      favour of kinetically stable complexes has remained elusive. Here, a review of
      the most recent observations in the field is presented, pointing to the
      possibility that DM decides the survival of a peptide-MHCII complex (pMHCII) on
      the basis of its conformational flexibility, which is a function of the
      'tightness' of interaction between the peptide and the MHCII at a specific region
      of the binding site.

PMID- 23113689
TI  - Predicting adolescents' disclosure of personal information in exchange for
      commercial incentives: an application of an extended theory of planned behavior.
AB  - This study adopts a global theoretical framework to predict adolescents'
      disclosure of personal information in exchange for incentives offered by
      commercial Websites. The study postulates and tests the validity of a model based
      on the theory of planned behavior (TPB), including antecedent factors of attitude
      and perceived behavioral control (PBC). A survey was conducted among 1,042
      respondents. Results from SEM analyses show that the hypothesized model fits the
      empirical data well. The model accounts for 61.9 percent of the variance in
      adolescents' intention to disclose and 43.7 percent of the variance in self
      reported disclosure. Perceived social pressure exerted by significant others
      (subjective norm) is the most important TPB factor in predicting intention to
      disclose personal information in exchange for incentives. This finding suggests
      that in discussions of adolescents' information privacy, the importance of social
      factors outweighs the individually oriented TPB factors of attitude and PBC.
      Moreover, privacy concern and trust propensity are significant predictors of
      respondents' attitudes toward online disclosure in exchange for commercial
      incentives, whereas the frequency of Internet use significantly affects their
      level of PBC.

PMID- 23113690
TI  - The impact of group membership on collaborative learning with wikis.
AB  - The social web stimulates learning through collaboration. However, information in
      the social web is often associated with information about its author. Based on
      previous evidence that ingroup information is preferred to outgroup information,
      the current research investigates whether group memberships of wiki authors
      affect learning. In an experimental study, we manipulated the group memberships
      (ingroup vs. outgroup) of wiki authors by using nicknames. The designated group
      memberships (being fans of a soccer team or not) were completely irrelevant for
      the domain of the wiki (the medical disorder fibromyalgia). Nevertheless, wiki
      information from the ingroup led to more integration of information into prior
      knowledge as well as more increase of factual knowledge than information from the
      outgroup. The results demonstrate that individuals apply social selection
      strategies when considering information from wikis, which may foster, but also
      hinder, learning and collaboration. Practical implications for collaborative
      learning in the social web are discussed.

PMID- 23113691
TI  - Internet and everyday life: the perceived implications of internet use on memory
      and ability to concentrate.
AB  - The growing role of Internet in all aspects of everyday life has led to
      speculations over the impacts beyond the traditional questions of access or
      sociability. This in mind, the main focus in this article was to examine how
      Finns, for majority of whom Internet use has become commonplace activity,
      perceive the impacts of Internet use since first adopting the technology. In this
      study, we examine how Internet user history and perceived computer skills, along
      with different sociodemographic factors, appear to reflect on the perceived
      impacts of Internet adoption in terms of memory and ability to concentrate.
      According to the results, almost one in five of the respondents reported changes
      concerning their memory or ability to concentrate, with skilled computer users
      and nonworkers, in particular, perceiving the change. Factors such as age-related
      differences and exposure to potential information overload at work were
      identified to explain the perceived change. Our data were collected in a survey
      gathering information on the everyday life and well-being of Finns. The sample
      consisted of 2000 Finnish speakers aged 15 to 64 years. The response rate was 46
      percent (N=908).

PMID- 23113692
TI  - Faced with a dilemma: Danish midwives' experiences with and attitudes towards
      late termination of pregnancy.
AB  - BACKGROUND: The introduction of prenatal screening for all pregnant women in
      Denmark in 2004 has lead to an increase in the number of late terminations of
      pregnancy after the 12th week of pregnancy. Midwives' experiences with late
      termination of pregnancy (TOP) are still poorly described in the scientific
      literature. AIM: To explore Danish midwives' experiences with and attitudes
      towards late TOP. Focus was on how midwives perceive their own role in late TOP,
      and how their professional identity is influenced by working with late TOP in a
      time where prenatal screening is rapidly developing. METHOD: A qualitative study
      consisting of ten individual interviews with Danish midwives, all of whom had
      taken part in late TOP. RESULTS: Current practice of late TOP resembles the
      practice of normal deliveries and is influenced by a growing personalisation of
      the aborted foetus. The midwives strongly supported women's legal right to choose
      TOP and considerations about the foetus' right to live were suppressed. Midwives
      experienced a dilemma when faced with aborted foetuses that looked like newborns
      and when aborted foetuses showed signs of life after a termination. Furthermore,
      they were critical of how physicians counsel women/couples after prenatal
      diagnosis. CONCLUSIONS: The midwives' practice in relation to late TOP was
      characterised by an acknowledgement of the growing ethical status of the foetus
      and the emotional reactions of the women/couples going through late TOP. Other
      professions as well as structural factors at the hospital highly influenced the
      midwives' ability to organize their work with late terminations. There is a need
      for more thorough investigation of how to secure the best possible working
      conditions for midwives, and how to optimise the care for women/couples going
      through late TOP.

PMID- 23113693
TI  - The use of moxifloxacin for acute exacerbations of chronic obstructive pulmonary
      disease and chronic bronchitis.
AB  - Chronic obstructive pulmonary disease is a common condition which causes
      considerable morbidity and mortality. It is a heterogenous disorder in which the
      majority of patients have chronic bronchitis. Bacterial infections are a major
      cause of acute exacerbations of both conditions which have a major impact on
      healthcare resources, quality of life and disease progression. Antibiotics are
      used to treat exacerbations involving purulent sputum production, together with
      increased breathlessness and/or sputum volume. Moxifloxacin is a quinolone
      antibiotic and is one of the treatment options. This article discusses
      pathophysiology of these diseases, moxifloxacin clinical studies and appropriate
      use of moxifloxacin.

PMID- 23113694
TI  - Clinicopathologic review of eruptive pseudoangiomatosis in Korean adults: report
      of 32 cases.
AB  - BACKGROUND: Eruptive pseudoangiomatosis (EP) is a rare, benign, spontaneously
      regressing exanthema of unknown etiology, characterized by an eruption of
      distinctive erythematous papules. This study was performed to evaluate the
      etiologic, clinical, and histopathologic characteristics of EP in Koreans.
      METHODS: Patients diagnosed with EP during 2005-2010 were included in a
      retrospective study. Diagnoses were based on clinical findings and confirmed by
      histology. Biopsies were re-examined. Patient gender, age at onset, disease
      duration, lesion location, season of occurrence, concomitant diseases,
      occupation, previous related events, disease course, responses to treatment, and
      laboratory findings were analyzed. RESULTS: A total of 32 patients were
      identified. Mean age at onset was 50.06 +/- 17.12 years. Two patients developed
      lesions after outdoor activities. Two patients presented with simultaneous
      occurrences in family members. One patient reported having taken herbal medicine.
      One subject experienced systemic contact dermatitis caused by eating a lacquer
      chicken dish just before the lesions developed. All patients had typical
      erythematous papules measuring 2-5 mm. Lesions were usually located on exposed
      sites. No prodromal or systemic symptoms were observed. Routine laboratory tests
      were within normal ranges, except in one patient with known hyperlipidemia. Most
      patients were treated with oral antihistamine and topical steroid, or oral
      prednisolone. Eight patients did not receive any treatment. Mean disease duration
      was 1.64 +/- 1.41 months in the treatment group and 1.20 +/- 1.24 months in the
      no-treatment group (P > 0.05). CONCLUSIONS: Any clear relationship between EP and
      exposure to allergens or insect bites has yet to be elucidated. In patients in
      whom EP occurs on non-exposed sites, drugs and food should be considered as
      possible causative agents. Intravascular neutrophil infiltration on histology can
      be helpful in diagnosing EP.

PMID- 23113695
TI  - Panic disorder in primary care: comorbid psychiatric disorders and their
      persistence.
AB  - OBJECTIVE: Although 70-80% of panic disorder patients use primary care to obtain
      mental health services, relatively few studies have examined panic patients in
      this setting. This study aimed to examine both the lifetime and current comorbid
      psychiatric disorders associated with panic disorder in primary care, the
      duration and severity of the disorder, and the sociodemographic factors
      associated with it. DESIGN: Patients were screened for panic disorder. Panic
      disorder and the comorbid disorders were determined using the Structured Clinical
      Interview for DSM-IV Axis I and II. SETTING: Eight different health care centers
      in primary care in the city of Espoo. SUBJECTS: Finnish-speaking, between 18 and
      65 years of age. MAIN OUTCOME MEASURES: Comorbid psychiatric disorders, the
      duration and severity of the disorder, and the sociodemographic factors. RESULTS:
      A sample of 49 panic disorder patients and 44 patients with no current
      psychiatric diagnosis were identified; 98% of panic disorder patients had at
      least one comorbid lifetime DSM-IV Axis I disorder. Major depressive disorder and
      other anxiety disorders were most common comorbid disorders. Lifetime alcohol use
      disorders also showed marked frequency. Interestingly, the remission rates of
      alcohol use disorders were notable. The panic symptoms appeared to persist for
      years. Panic disorder was associated with low education and relatively low
      probability of working full time. CONCLUSIONS: Also in primary care panic
      disorder is comorbid, chronic, and disabling. It is important to recognize the
      comorbid disorders. High remission rates of comorbid alcohol use disorders
      encourage active treatment of patients also suffering from these disorders.

PMID- 23113696
TI  - Amyloid fibril protein nomenclature: 2012 recommendations from the Nomenclature
      Committee of the International Society of Amyloidosis.
AB  - The Nomenclature Committee of the International Society of Amyloidosis (ISA) met
      during the XIIIth International Symposium, May 6-10, 2012, Groningen, The
      Netherlands, to formulate recommendations on amyloid fibril protein nomenclature
      and to consider newly identified candidate amyloid fibril proteins for inclusion
      in the ISA Amyloid Fibril Protein Nomenclature List. The need to promote
      utilization of consistent and up to date terminology for both fibril chemistry
      and clinical classification of the resultant disease syndrome was emphasized.
      Amyloid fibril nomenclature is based on the chemical identity of the amyloid
      fibril forming protein; clinical classification of the amyloidosis should be as
      well. Although the importance of fibril chemistry to the disease process has been
      recognized for more than 40 years, to this day the literature contains clinical
      and histochemical designations that were used when the chemical diversity of
      amyloid diseases was poorly understood. Thus, the continued use of disease
      classifications such as familial amyloid neuropathy and familial amyloid
      cardiomyopathy generates confusion. An amyloid fibril protein is defined as
      follows: the protein must occur in body tissue deposits and exhibit both affinity
      for Congo red and green birefringence when Congo red stained deposits are viewed
      by polarization microscopy. Furthermore, the chemical identity of the protein
      must have been unambiguously characterized by protein sequence analysis when so
      is practically possible. Thus, in nearly all cases, it is insufficient to
      demonstrate mutation in the gene of a candidate amyloid protein; the protein
      itself must be identified as an amyloid fibril protein. Current ISA Amyloid
      Fibril Protein Nomenclature Lists of 30 human and 10 animal fibril proteins are
      provided together with a list of inclusion bodies that, although intracellular,
      exhibit some or all of the properties of the mainly extracellular amyloid
      fibrils.

PMID- 23113697
TI  - Pharmacokinetics of cysteamine bitartrate following intraduodenal delivery.
AB  - Cysteamine is approved for the treatment of cystinosis and is being evaluated for
      Huntington's disease and non-alcoholic fatty liver disease. Little is known about
      the bioavailability and biodistribution of the drug. The aim was to determine
      plasma, cerebrospinal fluid (CSF), and tissue (liver, kidney, muscle) cysteamine
      levels following intraduodenal delivery of the drug in rats pretreated and naive
      to cysteamine and to estimate the hepatic first-pass effect on cysteamine.
      Healthy male rats (n = 66) underwent intraduodenal and portal (PV) or jugular
      (JVC) venous catheterization. Half were pretreated with cysteamine, and half were
      naive. Following intraduodenal cysteamine (20 mg/kg), serial blood samples were
      collected from the PV or the JVC. Animals were sacrificed at specific time
      points, and CSF and tissue were collected. Cysteamine levels were determined in
      plasma, CSF, and tissue. The Cmax was achieved in 5-10 min from PV and 5-22.5 min
      from JVC. The PV-Cmax (P = 0.08), PV-AUC0-t (P = 0.16), JVC-Cmax (P = 0.02) and
      JVC-AUC0-t (P = 0.03) were higher in naive than in pretreated animals. Plasma
      cysteamine levels returned to baseline in <=120 min. The hepatic first-pass
      effect was estimated at 40%. Peak tissue and CSF cysteamine levels occurred
      <=22.5 min, but returned to baseline levels <=180 min. There was no difference in
      CSF and tissue cysteamine levels between naive and pretreated groups, although
      cysteamine was more rapidly cleared in the pretreated group. Cysteamine is
      rapidly absorbed from the small intestine, undergoes significant hepatic first
      pass metabolism, crosses the blood brain barrier, and is almost undetectable in
      plasma, CSF, and body tissues 2 h after ingestion. Sustained-release cysteamine
      may provide prolonged tissue exposure. 

PMID- 23113698
TI  - Nontraumatic intradural and subdural hemorrhage and hypoxic ischemic
      encephalopathy in fetuses, infants, and children up to three years of age:
      analysis of two audits of 636 cases from two referral centers in the United
      Kingdom.
AB  - We analyzed the presence or absence of intradural hemorrhage (IDH) and subdural
      hemorrhage (SDH) and the degree of hypoxic-ischemic encephalopathy (HIE) in the
      brain of all nonmacerated fetuses of >24 weeks, neonates, and children up to 3
      years of age who died of natural causes over a defined period. We looked into the
      cause of death and the performance of cardiopulmonary resuscitation in our
      cohort. The IDH was classified as macroscopic or negative/microscopic only; the
      HIE was classified as absent, indeterminate, or definite. In fetuses, SDH with
      IDH was present in 22%; IDH alone was present in 31%, and there was no or minimal
      hemorrhage in 47% of cases. In infants and children SDH with IDH was present in
      19%; IDH alone was present in the 32%, and there was no or minimal hemorrhage in
      49% of cases. There was a statistically significant correlation between SDH and
      HIE, especially in infants and children (P < 0.001). When cases were grouped per
      age, a significant association between age and hemorrhage (P < 0.0001) was
      demonstrated, SDH being more common in infants <=1 month corrected age.
      Intradural hemorrhage can be the source of thin-film SDH in fetuses, infants, and
      young children. The presence of SDH is associated with hypoxia. Intradural and
      subdural hemorrhages are more common in autopsies of infants under 1 month
      corrected age. Although more rare, they can also be found in children between 1
      month and 3 years of age in the absence of trauma.

PMID- 23113699
TI  - Vapor phase deposition of functional polymers onto paper-based microfluidic
      devices for advanced unit operations.
AB  - Paper-based microfluidic devices have recently received significant attention as
      a potential platform for low-cost diagnostic assays. However, the number of
      advanced unit operations, such as separation of analytes and fluid manipulation,
      that can be applied to these devices has been limited. Here, we use a vapor phase
      polymerization process to sequentially deposit functional polymer coatings onto
      paper-based microfluidic devices to integrate multiple advanced unit operations
      while retaining the fibrous morphology necessary to generate capillary-driven
      flow. A hybrid grafting process was used to apply hydrophilic polymer coatings
      with a high surface concentration of ionizable groups onto the surface of the
      paper fibers in order to passively separate analytes, which allowed a
      multicomponent mixture to be separated into its anionic and cationic components.
      Additionally, a UV-responsive polymer was sequentially deposited to act as a
      responsive switch to control the path of fluid within the devices. This work
      extends the advanced unit operations available for paper-based microfluidics and
      allows for more complex diagnostics. In addition, the vapor phase polymerization
      process is substrate independent, and therefore, these functional coatings can be
      applied to other textured materials such as membranes, filters, and fabrics.

PMID- 23113700
TI  - The glmS ribozyme cofactor is a general acid-base catalyst.
AB  - The glmS ribozyme is the first natural self-cleaving ribozyme known to require a
      cofactor. The d-glucosamine-6-phosphate (GlcN6P) cofactor has been proposed to
      serve as a general acid, but its role in the catalytic mechanism has not been
      established conclusively. We surveyed GlcN6P-like molecules for their ability to
      support self-cleavage of the glmS ribozyme and found a strong correlation between
      the pH dependence of the cleavage reaction and the intrinsic acidity of the
      cofactors. For cofactors with low binding affinities, the contribution to rate
      enhancement was proportional to their intrinsic acidity. This linear free-energy
      relationship between cofactor efficiency and acid dissociation constants is
      consistent with a mechanism in which the cofactors participate directly in the
      reaction as general acid-base catalysts. A high value for the Bronsted
      coefficient (beta ~ 0.7) indicates that a significant amount of proton transfer
      has already occurred in the transition state. The glmS ribozyme is the first self
      cleaving RNA to use an exogenous acid-base catalyst.

PMID- 23113702
TI  - Diagnosis of narrow-band imaging in non-muscle-invasive bladder cancer: a
      systematic review and meta-analysis.
AB  - OBJECTIVES: The objective was to evaluate the diagnostic accuracy of cystoscopy
      assisted by narrow-band imaging compared with white-light imaging for non-muscle
      invasive bladder cancer. METHODS: An electronic database search of PubMed,
      Embase, the Cochrane Library, Ovid and Web of Science was carried out for all
      articles comparing narrow-band imaging with white-light imaging cystoscopy in the
      detection of non-muscle-invasive bladder cancer. The review process followed the
      guidelines of the Cochrane Collaboration. RESULTS: Seven studies with
      prospectively collected data including a total of 1040 patients were identified,
      and 611 patients with 1476 tumors were detected by biopsy. In the patient- and
      tumor-level analysis, an additional 17% of patients (95% confidence interval, 10
      25%) and an additional 24% of tumors (95% confidence interval, 17-31%) were
      detected by narrow-band imaging, respectively. In the patient- and tumor-level
      analysis, significantly higher detection rates using narrow-band imaging (rate
      difference 11%; 95% confidence interval 5-17%; P < 0.001; and rate difference
      19%; 95% confidence interval 12-26%; P < 0.001, respectively) rather than white
      light imaging were found. On the tumor level, an additional 28% of carcinoma in
      situ was detected (95% confidence interval 14-45%) by narrow-band imaging, and a
      significantly higher detection rate (rate difference 11%; 95% confidence interval
      1-21%; P = 0.03) was found. The false-positive detection rate of tumor level did
      not differ significantly between the two techniques. CONCLUSIONS: Cystoscopy
      assisted by narrow-band imaging detects more patients and tumors of non-muscle
      invasive bladder cancer than white-light imaging, and it might be an additional
      or alternative diagnostic technique for non-muscle-invasive bladder cancer.

PMID- 23113703
TI  - Postnatal outcome in neonates with severe Rhesus c compared to rhesus D hemolytic
      disease.
AB  - BACKGROUND: Neonates with Rhesus c (Rh c) hemolytic disease of the fetus and
      newborn (HDFN) are often managed in the same way as neonates with Rhesus D (Rh D)
      HDFN, although evidence to support this policy is limited. The objective of this
      study was to evaluate neonatal outcome in severe Rh c HDFN compared to Rh D HDFN.
      STUDY DESIGN AND METHODS: A retrospective study of (near-)term neonates with
      severe Rh c (n = 22) and Rh D HDFN (n = 103; without additional antibodies)
      admitted to the Leiden University Medical Center between January 2000 and October
      2011 was conducted. The need for intrauterine transfusions (IUTs), phototherapy,
      exchange transfusions (ETs), and top-up transfusions up to 3 months of age were
      recorded and compared between both groups. RESULTS: Although there was a trend
      for a slightly more severe antenatal course for Rh D HDFN reflected by an earlier
      need for and higher number of IUTs (median [interquartile range], 2 [1.5-4] vs. 2
      [1-2] in Rh c HDFN; p = 0.070), no significant differences were found for the
      postnatal course between Rh c and Rh D group in days of phototherapy (mean, Days
      4.8 and 4.6, respectively; p = 0.569), need for ET (50% vs. 44%, respectively; p
      = 0.589), and top-up transfusions (62% vs. 78%, respectively; p = 0.128).
      CONCLUSION: Postnatal outcome in neonates with severe Rh c HDFN is similar
      compared to neonates with severe Rh D hemolytic disease in terms of days of
      phototherapy, need for ET, and need for top-up transfusions. These results
      justify a similar postnatal management of neonates with Rh D and Rh c HDFN.

PMID- 23113704
TI  - Hybrid colloidal Au-CdSe pentapod heterostructures synthesis and their
      photocatalytic properties.
AB  - In this report, we present a self-driven chemical process to design exclusive
      Au/CdSe pentapod heterostructures with Au core and CdSe arms. We have analyzed
      these heterostructures using high-resolution transmission electron microscope
      (HRTEM), high angle annular dark field-scanning transmission electron microscopic
      (HAADF-STEM), X-ray diffraction, and X-ray photoelectron spectroscopy (XPS)
      studies. Microscopic studies suggest that pentapod arms of CdSe are nucleated on
      the (111) facets of Au and linearly grown only along the [001] direction. From
      the XPS study, the shifting of peak positions in the higher binding energy region
      for Au/CdSe heterostructures compared to Au nanoparticles has been found which
      indicates the charge transfer from CdSe to Au in heterostructures. The steady
      state and time resolved spectroscopic studies unambiguously confirm the electron
      transfer from photoexcited CdSe to Au, and the rate of electron transfer is found
      to be 3.58*108 s-1. It is interesting to note that 87.2% of R6G dye is degraded
      by the Au/CdSe heterostructures after 150 min UV irradiation, and the apparent
      rate constant for Au/CdSe heterostructures is found to be 0.013 min-1. This new
      class of metal-semiconductor heterostructures opens up new possibilities in
      photocatalytic, solar energy conversion, photovoltaic, and other new emerging
      applications.

PMID- 23113705
TI  - Protective effect of SnCl2 on K2Cr2O7-induced toxicity in LLC-PK1 cells.
AB  - The exposure to hexavalent chromium is often known to cause acute renal failure.
      It has been found that nonenzymatic antioxidants and the induction of heme
      oxygenase 1 have protective effects against nephrotoxicity induced by potassium
      dichromate in vivo. In this work, the effect of stannous chloride, an inducer of
      heme oxygenase 1, on potassium dichromate-induced toxicity in proximal tubular
      epithelial cells was studied. Hexavalent chromium levels, peroxynitrite content,
      reduced thiol content, heme oxygenase activity, reactive oxygen species
      production, and stannous chloride scavenging capacity were measured. It was found
      that stannous chloride protects proximal tubular epithelial cells from potassium
      dichromate-induced cell death. The decrease in extracellular and intracellular
      hexavalent chromium concentration, the induction of heme oxygenase 1, and the
      ability to scavenge reactive oxygen species and peroxynitrite are involved in the
      mechanism by which stannous chloride protects proximal tubular epithelial cells
      from potassium dichromate-induced toxicity.

PMID- 23113706
TI  - Determining protein structures from NOESY distance constraints by semidefinite
      programming.
AB  - Contemporary practical methods for protein nuclear magnetic resonance (NMR)
      structure determination use molecular dynamics coupled with a simulated annealing
      schedule. The objective of these methods is to minimize the error of deviating
      from the nuclear overhauser effect (NOE) distance constraints. However, the
      corresponding objective function is highly nonconvex and, consequently, difficult
      to optimize. Euclidean distance matrix (EDM) methods based on semidefinite
      programming (SDP) provide a natural framework for these problems. However, the
      high complexity of SDP solvers and the often noisy distance constraints provide
      major challenges to this approach. The main contribution of this article is a new
      SDP formulation for the EDM approach that overcomes these two difficulties. We
      model the protein as a set of intersecting two- and three-dimensional cliques.
      Then, we adapt and extend a technique called semidefinite facial reduction to
      reduce the SDP problem size to approximately one quarter of the size of the
      original problem. The reduced SDP problem can be solved approximately 100 times
      faster, and it is also more resistant to numerical problems from erroneous and
      inexact distance bounds.

PMID- 23113707
TI  - Plasma and urine concentrations of bioactive dietary benzoxazinoids and their
      glucuronidated conjugates in rats fed a rye bread-based diet.
AB  - Thorough knowledge of the absorption and metabolism of dietary benzoxazinoids is
      needed to understand their health-promoting effects. In this study, the fates of
      these bioactive compounds were examined by LC-MS/MS in plasma, urine, and feces
      after ingesting a daily dose of 4780 +/- 68 nmol benzoxazinoids from rye bread
      using Wistar rats as a model. HBOA-glc (2-beta-D-glucopyranosyloxy-1,4-benzoxazin
      3-one) was the predominant benzoxazinoid in the plasma (74 +/- 27 nmol/L),
      followed by DIBOA-glc (2-beta-D-glucopyranosyloxy-4-hydroxy-1,4-benzoxazin-3-one)
      and HBOA. The total level of benzoxazinoids in the urine was 1176 +/- 66 nmol/d,
      which corresponds to approximately 25% of the total dietary intake. The urinary
      benzoxazinoid profile differed from that of plasma with HBOA-glc and DIBOA-glc
      (647 +/- 31 and 466 +/- 33 nmol/d, respectively) as the major urinary components.
      The glucuronide conjugates of HBOA and DIBOA were detected in both the plasma and
      urine. N-dehydroxylation was found to be a critical step in the absorption of
      hydroxamic acids. This unprecedented study will trigger future interest in the
      biological effects of benzoxazinoids in whole grain rye and wheat diets in humans
      and other animals.

PMID- 23113708
TI  - Severe sepsis and systemic inflammatory response syndrome in emergency department
      patients with suspected severe infection.
AB  - BACKGROUND: Severe sepsis is a common condition with a reported high mortality,
      but most studies have been confined to intensive care unit (ICU) populations. The
      systemic inflammatory response syndrome (SIRS) has been used to define sepsis,
      however its usefulness has been questioned. Our aim was to describe the
      prevalence and clinical impact of severe sepsis and SIRS in patients admitted
      from the emergency department (ED) with a suspected serious infection. METHODS:
      Four hundred and four adult patients were enrolled prospectively from the ED.
      Variables defining severe sepsis and SIRS were measured and the relationship
      between severe sepsis, SIRS, and the clinical course was analyzed. RESULTS:
      Infections were diagnosed in 344 patients (85%). The overall mortality rate at 28
      days was 2.7%, and 4.5% of patients were treated in the ICU. Patients with severe
      sepsis within 24 h of admission (42%) were more likely to suffer a critical
      course (ICU admission 9.0%, death 5.1%; p < 0.001). While SIRS was observed in
      72% of the subjects at presentation, it was not associated with severe sepsis
      within 24 h or a subsequent critical course. Furthermore, 23% of patients with
      severe sepsis within 24 h did not present with SIRS. CONCLUSIONS: Severe sepsis
      was a common condition among ED patients with a clinically suspected serious
      infection. Mortality was low compared with results from the ICU setting,
      suggesting that severe sepsis is a more benign disease than earlier reported. As
      a tool for the definition of sepsis and for the selection of patients for
      clinical sepsis trials, SIRS lacks acceptable discriminative ability in an ED
      population with a high prevalence of serious infections.

PMID- 23113709
TI  - Cationic zirconium hydrides supported by an NNNN-type macrocyclic ligand:
      synthesis, structure, and reactivity.
AB  - An air- and light-sensitive, but thermally stable
      tris[(trimethylsilyl)methyl]zirconium complex containing an NNNN-type macrocyclic
      ligand [Zr(Me3TACD)(CH2SiMe3)3] (1; Me3TACD = Me3[12]aneN4: 1,4,7-trimethyl
      1,4,7,10-tetraazacyclododecane) was prepared by reacting [Zr(CH2SiMe3)4] with
      (Me3TACD)H. Reaction of the zirconium tris(alkyl) 1 with a Lewis or Bronsted acid
      gave a dialkyl cation with a weakly coordinating anion
      [Zr(Me3TACD)(CH2SiMe3)2][A] [A = Al{OC(CF3)3}4 (2a), B{3,5-C6H3(CF3)2}4 (2b),
      B(3,5-C6H3Cl2)4 (2c), and BPh4) (2d)]. Hydrogenolysis of 2a-2c resulted in the
      formation of the dinuclear tetrahydride dication [{Zr(Me3TACD)(MU-H)2}2][A]2 (3a
      3c). Compounds 1-3 were characterized by multinuclear NMR spectroscopy, and the
      solid-state structures of 1, 2c, and 3b were established by single-crystal X-ray
      diffraction studies. The dinuclear hydride complex 3b exhibits a quadruply
      bridged {Zr2(MU-H)4} core in solution and in the solid state with a relatively
      short Zr...Zr distance of 2.8752(11) A. Density functional theory computations at
      the B3PW91 level reproduced this structure (Zr...Zr distance of 2.900 A). The
      cationic hydride complex 3b reacted with excess carbon monoxide in
      tetrahydrofuran at room temperature to give ethylene in 25% yield based on 3b.
      Upon analysis of (13)C NMR spectra of the reaction mixture using (13)CO,
      oxymethylene and enolate complexes were detected as intermediates among other
      complexes. 

PMID- 23113710
TI  - Editorial: aliskiren/amlodipine single-pill combinations: more evidence in favour
      of combination formulations for the treatment of hypertension.
AB  - In this issue of Curr Vasc Pharmacol, Pfeiffer et al. [1] and Glorioso et al. [2]
      report the efficacy and tolerability of aliskiren/amlodipine single-pill
      combinations (SPCs) in patients with inadequate blood pressure (BP) response to
      amlodipine or aliskiren monotherapy, respectively.

PMID- 23113711
TI  - Colorectal neoplasia and pyogenic liver abscess.

PMID- 23113712
TI  - Combination peptide immunotherapy based on T-cell epitope mapping reduces
      allergen-specific IgE and eosinophilia in allergic airway inflammation.
AB  - Peptide immunotherapy using soluble peptides containing allergen-derived
      immunodominant T-cell epitopes holds therapeutic promise for allergic asthma.
      Previous studies in BALB/c mice using the immunodominant peptide epitope of
      chicken ovalbumin (p323-339) have been unable to demonstrate therapeutic effects
      in ovalbumin-induced allergic airway inflammation. We have previously shown that
      intravenous application of p323-339 can effectively tolerise p323-339-reactive T
      cells in a non-allergic model in C57BL/6 mice. This study aimed to assess the
      effects of using p323-339 immunotherapy in a C57BL/6 model of ovalbumin-induced
      allergic airway inflammation, identify any additional epitopes recognized by the
      ovalbumin-responsive T-cell repertoire in C57BL/6 mice and assess the effects of
      combination peptide immunotherapy in this model. Ovalbumin-reactive T-cell lines
      were generated from ovalbumin-immunized C57BL/6 mice and proliferative responses
      to a panel of overlapping peptides covering the ovalbumin sequence were assessed.
      Soluble peptides (singly or combined) were administered intravenously to C57BL/6
      mice before the induction of ovalbumin-induced allergic airway inflammation.
      Peptide immunotherapy using the 323-339 peptide alone did not reduce the severity
      of allergic airway inflammation. An additional immunodominant T-cell epitope in
      ovalbumin was identified within the 263-278 sequence. Combination peptide
      immunotherapy, using the 323-339 and 263-278 peptides together, reduced
      eosinophilia in the bronchoalveolar lavage and ovalbumin-specific IgE, with
      apparent reductions in interleukin-5 and interleukin-13. Characterization of the
      T-cell response to a model allergen has allowed the development of combination
      peptide immunotherapy with improved efficacy in allergic airway inflammation.
      This model holds important potential for future mechanistic studies using peptide
      immunotherapy in allergy.

PMID- 23113713
TI  - A metabolic regulator modulates virulence and quorum sensing signal production in
      Pectobacterium atrosepticum.
AB  - Plant cell wall-degrading enzymes (PCWDE) are key virulence determinants in the
      pathogenesis of the potato pathogen Pectobacterium atrosepticum. In this study,
      we report the impact on virulence of a transposon insertion mutation in the metJ
      gene that codes for the repressor of the methionine biosynthesis regulon. In a
      mutant strain defective for the small regulatory RNA rsmB, PCWDE are not produced
      and virulence in potato tubers is almost totally abolished. However, when the
      metJ gene is disrupted in this background, the rsmB(-) phenotype is suppressed
      and virulence and PCWDE production are restored. Additionally, when metJ is
      disrupted, production of the quorum-sensing signal, N-(3-oxohexanoyl)-homoserine
      lactone, is increased. The metJ mutant strains showed pleiotropic transcriptional
      impacts affecting approximately a quarter of the genome. Genes involved in
      methionine biosynthesis were most highly upregulated but many virulence
      associated transcripts were also upregulated. This is the first report of the
      impact of the MetJ repressor on virulence in bacteria.

PMID- 23113714
TI  - Genetic determinants of Potato virus Y required to overcome or trigger
      hypersensitive resistance to PVY strain group O controlled by the gene Ny in
      potato.
AB  - Potato virus Y (PVY) (genus Potyvirus) is the most economically damaging and
      widely distributed virus in potato. Spread of PVY in the field is controlled by
      growing resistant cultivars. The dominant potato gene Ny(tbr) for hypersensitive
      resistance (HR) controls ordinary PVY strains (PVY(O)) but is overcome by PVY(N)
      strains. Studies with infectious PVY chimeras and mutants indicated that the
      viral determinants necessary and sufficient to overcome Ny(tbr) reside within the
      helper component proteinase (HC-Pro) (residues 227 to 327). Specifically, eight
      residues and the modeled three-dimensional conformation of this HC-Pro region
      distinguish PVY(N) from PVY(O) strains. According to the model, the conserved IGN
      and CCCT motifs implicated in potyvirus replication and movement, respectively,
      are situated in a coiled structure and an alpha-helix, respectively, within this
      region in PVY(O); however, their locations are reversed in PVY(N). Two residues
      (R269 and K270) are crucial for the predicted PVY(O)-specific HC-Pro
      conformation. Two viral chimeras triggered Ny(tbr) and induced veinal necrosis in
      tobacco, which is novel for PVY. One chimera belonged to strain group PVY(E). Our
      results suggest a structure-function relationship in recognition of PVY(O) HC-Pro
      by Ny(tbr), reveal HC-Pro amino acid signatures specific to PVY(O) and PVY(N),
      and facilitate identification of PVY strains overcoming Ny(tbr).

PMID- 23113715
TI  - CA15.3, CEA and LDH in dogs with malignant mammary tumors.
AB  - BACKGROUND: Presence of tumor markers in serum might be connected to the number
      of secreting cells and with the stage of the neoplasm. However, there are few
      studies regarding these markers in veterinary clinical oncology. OBJECTIVES: To
      determine the serum concentrations of cancer antigen 15.3 (CA 15.3),
      carcinoembryonic antigen (CEA), and lactate dehydrogenase (LDH) in female dogs
      with different stages of mammary cancer. ANIMALS: Ninety female dogs, including
      30 that were healthy, 40 that had nonmetastatic cancer, 12 with regional
      metastasis, and 8 with distant lymph node metastasis. METHODS: Prospective case
      controlled observational study. Serum samples were collected to measure CA15.3,
      CEA, and LDH from 60 female dogs with mammary cancer during mastectomy and 30
      healthy female dogs during routine check-up. CA15.3 and CEA were determined by
      chemiluminescent immunoassay and LDH by ultraviolet kinetic method. Western
      blotting analysis was performed to confirm the specificity and possible cross
      reactivity of human CA15.3 and CEA antibodies with canine serum. Group data were
      compared by ANOVA followed by Student-Newman-Keuls and Tukey's tests.
      Correlations were investigated by Pearson and Spearman tests. RESULTS: CEA,
      CA15.3, and LDH were measurable in all groups. Higher serum concentration of
      CA15.3 and LDH was associated with regional and distant metastases. There was a
      significantly higher serum CA15.3 concentration in animals with lymph node
      metastasis when compared with animals without metastasis. There were no
      significant differences in CEA among groups. Expression of CA15.3 and CEA in
      canine serum was confirmed by Western blotting. CONCLUSIONS AND CLINICAL
      IMPORTANCE: Serum CA15.3 can be used to distinguish nonmetastatic from metastatic
      carcinomas.

PMID- 23113717
TI  - Tyrosinase inhibitors from the wood of Artocarpus heterophyllus.
AB  - From the methanolic-soluble extract of the wood of Artocarpus heterophyllus, four
      new flavones, artocarmins A-D (1-4), and three new chalcones, artocarmitins A-C
      (5-7), have been isolated together with 13 known compounds. Their structures were
      determined on the basis of the spectroscopic data. Compounds 1-4, 6, 7, 9-16, and
      20 displayed significant tyrosinase inhibitory activity. The most active
      compound, morachalcone A (12) (IC50, 0.013 MUM), was 3000 times more active as a
      tyrosinase inhibitor than a positive control, kojic acid (IC50, 44.6 MUM). 

PMID- 23113716
TI  - Palladium-catalyzed desulfitative arylation by C-O bond cleavage of aryl
      triflates with sodium arylsulfinates.
AB  - An efficient Pd-catalyzed desulfitative coupling reaction of sodium
      arylsulfinates as arylation reagents by C-O bond cleavage of aryl triflates was
      developed. With only 2 mol % of Pd(OAc)(2) as catalyst and XPhos as ligand, the
      reaction proceeded well for a range of substrates.

PMID- 23113718
TI  - Axial SiGe heteronanowire tunneling field-effect transistors.
AB  - We present silicon-compatible trigated p-Ge/i-Si/n-Si axial heteronanowire
      tunneling field-effect transistors (TFETs), where on-state tunneling occurs in
      the Ge drain section, while off-state leakage is dominated by the Si junction in
      the source. Our TFETs have high I(ON) ~ 2 MUA/MUm, fully suppressed ambipolarity,
      and a subthreshold slope SS ~ 140 mV/decade over 4 decades of current with lowest
      SS ~ 50 mV/decade. Device operation in the tunneling mode is confirmed by three
      dimensional TCAD simulation. Interestingly, in addition to the TFET mode, our
      devices work as standard nanowire FETs with a good I(ON)/I(OFF) ratio when the
      source-drain junction is forward-biased. The improved transport in both biasing
      modes confirms the benefits of utilizing bandgap engineered axial nanowires for
      enhancing device performance.

PMID- 23113719
TI  - Amyloid A deposition in rheumatoid arthritis: a retrospective clinicopathologic
      study of 161 autopsy patients.

PMID- 23113720
TI  - 2,3,4,5-Tetrakis(3',4'-dihydroxylphenyl)thiophene: a new matrix for the selective
      analysis of low molecular weight amines and direct determination of creatinine in
      urine by MALDI-TOF MS.
AB  - Small organic matrixes are still the most commonly used ones in matrix-assisted
      laser desorption/ionization mass spectrometry (MALDI MS) because of their
      advantages of high sensitivity, convenience, and cost-effectiveness. However, due
      to the matrix interference in the low mass region, the direct analysis of low
      molecular weight amines in complex surroundings with conventional organic
      matrixes remains a challenge. Here, a new Bronsted-Lowry acid compound 2,3,4,5
      tetrakis(3',4'-dihydroxylphenyl)thiophene (DHPT) was designed, synthesized, and
      applied as a matrix for analysis of low molecular weight amines by MALDI-TOF MS.
      DHPT displays good selectivity in the analysis of amines without matrix-related
      interference and the low picomole/femtomole limit-of-detection was obtained in
      positive ion mode. With DHPT, the metabolites including creatinine, glycine,
      alloxan, allantoin, and 3-hydroxyhippuric acid in human urine were directly
      analyzed by MALDI-TOF MS. The identity of these metabolites was confirmed by
      tandem mass spectrometry. Furthermore, the urine creatinine was quantitatively
      determined using isotope-labeled internal standard. This DHPT-assisted LDI MS
      method provides a general approach for both qualitative and quantitative analysis
      of low molecular weight amines.

PMID- 23113721
TI  - Outcome of extremely low gestational age newborns after introduction of a revised
      protocol to assist preterm infants in their transition to extrauterine life.
AB  - AIM: To evaluate the outcome of a cohort of extremely low gestational age newborn
      infants (ELGAN) below 26-week gestation who were treated following a revised,
      gentle delivery room protocol to assist them in the transition and adaptation to
      extrauterine life. METHODS: A cohort of infants with a gestational age (GA) below
      26 weeks (study group; n = 164) was treated according to a revised delivery room
      protocol. The protocol included an optimized prenatal management, strict use of
      continuous positive airway pressure (CPAP), avoiding mechanical ventilation and
      early administration of surfactant without intubation. The parameters management
      of respiratory distress syndrome, survival, neonatal morbidity and
      neurodevelopmental outcome were compared with a historical control group (n =
      44). RESULTS: Seventy-four per cent of the study group infants were initially
      treated with CPAP and surfactant administration without intubation. In comparison
      with the control group, significantly less children were intubated in the
      delivery room (24% vs. 41%) and needed mechanical ventilation (51% vs. 72%; both
      p < 0.05). Furthermore, compared with the historical control overall mortality
      (20% vs. 39%), rate of bronchopulmonary dysplasia (18% vs. 37%) and IVH > II
      degrees  (10% vs. 33%) in survivors were significantly lower during the
      observational period (all p < 0.05). Neurodevelopmental outcome was normal in 70%
      of examined study group infants. CONCLUSIONS: A revised delivery room management
      protocol was applied safely to infants with a GA below 26 completed weeks with
      improved rates of survival and morbidity.

PMID- 23113722
TI  - Sweet's syndrome and acute parvovirus B19 infection.

PMID- 23113723
TI  - Cystic malformation of lower female genital tract resulting in hydrops fetalis: a
      case report.
AB  - Genitourinary tract malformations causing hydrops fetalis are rare. The authors
      report a case of a female delivered at 32 weeks gestational age following a
      prenatal diagnosis of an abdominopelvic cystic mass with hydrops fetalis. The
      neonate was persistently hypoxic with unstable cardiovascular status and survived
      only 7 days. At autopsy, a cystic malformation replaced the vagina and uterus,
      associated with lower vaginal atresia and anorectal agenesis. The cyst had
      interfered with the normal process of Mullerian duct fusion, leading to a
      longitudinal vaginal septum and bifurcation of endocervix, with absent uterus and
      fallopian tubes. The urinary bladder was compressed by the cyst, resulting in
      bilateral hydronephrosis. The cyst impeded the inferior vena caval and umbilical
      venous circulations and impinged upon the thoracic cavity with resultant
      pulmonary hypoplasia. This malformation, which might be termed "cystic dysplasia"
      of the vagina, represents an extreme form of hydrometrocolpos that resulted in
      hydrops fetalis.

PMID- 23113724
TI  - Echinococcosis in Serbia: an issue for the 21st century?
AB  - Echinococcosis (hydatidosis) is traditionally endemic in Southeast Europe, Serbia
      included. In Serbia, echinococcosis is mandatory reportable, and this review
      analyzes the officially reported data as well as the research data published
      between 1998 and 2010. Official data on human and animal infections were obtained
      from the Institute of Public Health of Serbia (IPHS, 2010), and from the Ministry
      of Agriculture, Trade, Forestry and Water Management (MATFWM) and the Statistical
      Office, respectively. Published data were obtained by searching the Medline,
      Scopus, and Google databases using "echinococcosis," "hydatidosis," and "Serbia"
      as key words. In addition, the search included national journals and doctoral
      theses, as well as conference proceedings. Only Echinococcus granulosus has been
      reported in Serbia, with a total of 409 cases of human infection officially
      reported during the observed period as opposed to 820 cases described in clinical
      studies. No trend in the incidence of infection was shown among adults, but the
      number of cases in children continuously decreased over the period. Patients were
      more frequently female and from rural areas. Differences in the geographic
      distribution of cases were noted, with a lower incidence in the central part of
      country. Liver disease was by far the most common presentation, but cases of
      unusual cyst locations have been described. Among domestic animals, sheep were
      the most highly infected species. A decreasing incidence of echinococcosis in
      animals has been noted as of the 1970s. Echinococcosis continues to be endemic in
      Serbia in the 21st century, but despite predictions, neither official data nor
      those from clinical studies indicate its re-emergence. However, there is gross
      underreporting. Public health authorities should actively work to increase
      reporting, as only valid reported data provide an accurate basis for future
      control plans.

PMID- 23113725
TI  - Survival and inactivation of human norovirus surrogates in blueberry juice by
      high-pressure homogenization.
AB  - Human noroviruses (HNoV) have been implicated in gastrointestinal outbreaks
      associated with fresh produce, juices, and ready-to-eat foods. In order to
      determine the risk of HNoV transmission by contaminated blueberry juice, survival
      characteristics of cultivable HNoV surrogates (murine norovirus, MNV-1; feline
      calicivirus, FCV-F9; and bacteriophage MS2) in blueberry juice (pH = 2.77) after
      0, 1, 2, 7, 14, and 21 days at refrigeration temperatures (4 degrees C) were
      studied. High-pressure homogenization (HPH) was studied as a novel processing
      method for noroviral surrogate inactivation in blueberry juice. Blueberry juice
      or phosphate-buffered saline (PBS; pH 7.2 as control) was inoculated with each
      virus, stored over 21 days at 4 degrees C or subjected to HPH, and plaque
      assayed. FCV-F9 (~5 log(10) PFU/mL) was undetectable after 1 day in blueberry
      juice at 4 degrees C. MNV-1 (~4 log(10) PFU/ml) showed minimal reduction (1
      log(10) PFU/mL) after 14 days, with greater reduction (1.95 log(10) PFU/mL; p <
      0.05) after 21 days in blueberry juice at 4 degrees C. Bacteriophage MS2 (~6
      log(10) PFU/mL) showed significant reduction (1.93 log(10) PFU/mL; p < 0.05)
      after 2 days and was undetectable after 7 days in blueberry juice at 4 degrees C.
      FCV-F9 remained viable in PBS for up to 21 days (2.28 log(10) PFU/mL reduction),
      while MNV-1 and MS2 survived after 21 days (1.08 and 0.56 log(10) PFU/mL
      reduction, respectively). Intriguingly, FCV-F9 and bacteriophage MS2 showed
      reduction after minimal homogenization pressures in blueberry juice (pH = 2.77),
      possibly due to the combination of juice pH, juice components, and mechanical
      effects. MNV-1 in blueberry juice was only slightly reduced at 250 (0.33 log(10)
      PFU/mL) and 300 MPa (0.71 log(10) PFU/mL). Virus surrogate survival in blueberry
      juice at 4 degrees C correlates well with the ease of HNoV transmission via
      juices. HPH for viral inactivation in juices is dependent on virus type, and
      higher homogenization pressures may be needed for MNV-1 inactivation.

PMID- 23113726
TI  - How do I provide leukapheresis products? Blood center experience and evidence for
      process improvement.
AB  - BACKGROUND: The past few decades have seen a resurgence of interest in
      leukapheresis products to improve the survival of infected patients with
      neutropenia. These products have a short shelf life and require donor stimulation
      with dexamethasone before collection. Additionally, a system with good
      communications and logistical support is essential. A recent survey of blood
      centers in North America revealed that the majority of centers collecting
      leukapheresis products use steroid-stimulated donors. The survey results
      suggested that an analysis of the process and potential process improvement would
      be of interest to the transfusion medicine community. STUDY DESIGN AND METHODS:
      Data from 2008 to 2011 regarding donor selection, donor dexamethasone
      stimulation, leukapheresis collection, and correlations between potentially
      pertinent variables for process improvement were analyzed. Results from an
      analysis of cost are also included. RESULTS: We evaluate 432 leukapheresis
      donations and demonstrate correlations between 1) pre- and poststimulation white
      blood cell (WBC) count (p<0.0001), 2) interval (donor stimulation to collection)
      and poststimulation WBC count (p<0.0001), and 3) poststimulation WBC count and
      leukapheresis product granulocyte yield (p<0.0001). CONCLUSIONS: Significant
      improvement in granulocyte quality and yield can be accomplished in dexamethasone
      stimulated donors, by selecting eligible donors with relatively high normal
      prestimulation WBC counts and/or previously good responses to dexamethasone,
      increasing the duration between dexamethasone stimulation and granulocyte
      collection, and maintaining optimal hematocrit (5%-10%) in granulocyte
      collections. Because the majority of surveyed blood centers collecting stimulated
      granulocytes use steroids alone, modifications presented here may prove useful.
      Further assessment of correlation between granulocyte yield and clinical outcome
      will await results of additional studies.

PMID- 23113728
TI  - Anodization of Pd in H2SO4 solutions: influence of potential, polarization time,
      and electrolyte concentration.
AB  - The anodization of Pd in H2SO4 solutions has been investigated by electrochemical
      measurements, considering the effect of the applied potential, polarization time,
      and electrolyte concentration. The anodization and subsequent reduction result in
      the formation of Pd nanostructures on the electrode surface. Compared to the bulk
      Pd, the anodization of Pd in H2SO4 solutions leads to different cyclic
      voltammetry (CV) behaviors including well-separated adsorption/desorption peaks
      in the hydrogen region and relatively larger reduction peak areas. The
      improvement of electrochemically active surface areas (EASAs) of the anodized Pd
      samples is strongly dependent upon the electrolyte concentration, and the optimum
      H2SO4 concentration is 1.0 M. Both the applied potential and polarization time
      have a significant influence on the anodization process of Pd. For the given
      electrolyte concentration, there exist desirable applied potential and
      polarization time to achieve greater EASAs. The EASAs of the anodized Pd obtained
      under the optimum polarization conditions can reach as large as 890 times
      compared to its geometric area. In addition, the formation mechanism of Pd
      nanostructures on the electrode surface has been discussed on the basis of
      microstructural analysis. The present findings provide a promising route to
      fabricate nanostructured Pd electrocatalysts with ultrahigh EASAs.

PMID- 23113729
TI  - Production of antibodies and development of enzyme-linked immunosorbent assay for
      valnemulin in porcine liver.
AB  - Polyclonal and monoclonal antibodies against valnemulin, a new semi-synthetic
      antibiotic derivative of pleuromutilin administered to treat swine dysentery and
      pneumonia, were generated. To achieve high enzyme-linked immunosorbent assay
      sensitivity for valnemulin, several heterologous coating antigens were prepared
      and evaluated, differing in the length of the spacer arm and the conjugation site
      between valnemulin and carrier protein. After the optimisation of immuno-reagents
      dilution, the enzyme-linked immunosorbent assay, based on polyclonal antibody
      number 2 and one heterologous coating antigen, showed the highest sensitivity
      with an IC(50) value for valnemulin of 0.96 ng/mL in buffer. For spiked porcine
      liver, an extraction procedure with a mixture of acetonitrile and 0.01 M
      hydrochloric acid (40:60 v/v) was proposed and no further sample pre-treatment
      other than 10 times dilution of the extract was necessary prior to analysis,
      which gave recovery values ranging from 75.7% to 89.4%. The dynamic assay range
      and the limit of detection of the assay were 2.4-49.9 and 1.67 ug/kg for porcine
      liver, respectively. The assay was compared with a confirmation method based on
      LC-MS/MS by using valnemulin-treated samples, and a satisfactory correlation
      between both methods was observed.

PMID- 23113730
TI  - Three hydrogen bond donor catalysts: oxyanion hole mimics and transition state
      analogues.
AB  - Enzymes and their mimics use hydrogen bonds to catalyze chemical transformations.
      Small-molecule transition state analogues of oxyanion holes have been
      characterized by computations, gas-phase IR and photoelectron spectroscopy, and
      determination of their binding constants in acetonitrile. A new class of hydrogen
      bond catalysts is proposed (donors that can contribute three hydrogen bonds to a
      single functional group) and demonstrated in a Friedel-Crafts reaction. The
      employed catalyst was observed to react 100 times faster than its rotamer that
      can employ only two hydrogen bonds. The former compound also binds anions more
      tightly and was found to have a thermodynamic advantage.

PMID- 23113731
TI  - High frequency of co-resistance in CTX-M-producing Escherichia coli to non-beta
      lactam antibiotics, with the exceptions of amikacin, nitrofurantoin, colistin,
      tigecycline, and fosfomycin, in a county of Sweden.
AB  - BACKGROUND: The objective of this study was to investigate the in vitro activity
      of different antibiotics against CTX-M-producing Escherichia coli in a county of
      Sweden, and to determine the occurrence of multi-resistance and plasmid- mediated
      quinolone resistance among these isolates. METHODS: A total of 198 isolates of E.
      coli with extended-spectrum beta-lactamase (ESBL) phenotype and mainly CTX-M
      genotype were studied. The minimum inhibitory concentrations (MICs) for amikacin,
      chloramphenicol, ciprofloxacin, colistin, fosfomycin, gentamicin, nalidixic acid,
      nitrofurantoin, tigecycline, tobramycin, trimethoprim, and trimethoprim
      sulfamethoxazole were determined with the Etest. Susceptibility was defined
      according to the breakpoints of the European Committee on Antimicrobial
      Susceptibility Testing (EUCAST). MIC50 and MIC90 values were calculated. RESULTS:
      Ninety-five percent or more of the isolates were susceptible to amikacin,
      nitrofurantoin, colistin, tigecycline, and fosfomycin. CTX-M group 9 was more
      susceptible than CTX-M group 1 to ciprofloxacin, gentamicin, and tobramycin.
      Sixty-eight percent of the isolates were multi-resistant, and the most common
      multi-resistance pattern was ESBL phenotype with decreased susceptibility to
      trimethoprim, trimethoprim-sulfamethoxazole, ciprofloxacin, gentamicin, and
      tobramycin. Only 1 isolate carried a qnrS1 gene, but 37% carried aac(6')-Ib-cr.
      CONCLUSIONS: A high frequency of co-resistance between ESBL-producing E. coli and
      non-beta-lactam antibiotics was seen. On the other hand, very high susceptibility
      was seen for amikacin, nitrofurantoin, colistin, tigecycline, and fosfomycin.
      These data support the replacement of gentamicin and tobramycin, normally used in
      Sweden, with amikacin, for severe infections.

PMID- 23113732
TI  - Validation of the Whooley questions and the Beck Depression Inventory in older
      adults.
AB  - OBJECTIVE: To analyse the psychometric properties of the Whooley questions and
      the 21-item Beck Depression Inventory (BDI-21) in older adults with depression
      and chronic health problems. DESIGN: A population-based study. SETTING:
      Community. SUBJECTS: 474 adults, aged 72-73 years, living in the city of Oulu,
      Finland. MAIN OUTCOME MEASURES: The screening parameters of the Whooley questions
      and the BDI-21 for detecting major depression. RESULTS: The prevalence of major
      depression according to the DSM-IV was 5.3% (single or recurrent episode)
      obtained by the Mini Neuropsychiatric Interview (MINI). The BDI-21 was best able
      to identify a current episode of major depression with a cut-off point of 11. The
      sensitivity and specificity of this cut-off point were 88.0% (95% confidence
      interval (95% CI) 68.8-97.5) and 81.7% (95% CI 77.8-85.2), respectively. The area
      under the receiver operating characteristics (ROC) curve was 0.89 (95% CI 0.83
      0.96). The two Whooley screening questions had a sensitivity of 62.5% (95% CI
      40.6-81.2) and either screening question plus the help question had a sensitivity
      of 66.7% (44.7-84.4). CONCLUSIONS: The Beck Depression Inventory is a valid
      instrument for the diagnosis of depression in older adults. As a screening
      measure, the optimal cut-off score should be 11 or higher. Our results indicate
      that the sensitivity of the Whooley questions is not high enough to be used as a
      screening scale among the elderly.

PMID- 23113733
TI  - Chronic hepatitis C virus hepatitis and psoriasis: no longer a contraindication
      to interferon use in the era of biological agents?
AB  - We describe a patient with severe psoriasis and hepatitis C simultaneously
      treated with pegylated interferon alpha (peg-IFNalpha) plus ribavirin and
      etanercept, whose skin lesions improved and who reached a sustained virological
      response. This case suggests that refractory psoriasis can today no longer be
      considered as a contraindication for combined hepatitis C virus treatment.

PMID- 23113734
TI  - Biomarkers for lower urinary tract dysfunction.
AB  - Lower urinary tract dysfunction is highly prevalent, but has relatively low
      persistence and compliance with therapy because of poor efficacy. Although
      urodynamic study is the gold standard for detailed evaluation of lower urinary
      tract dysfunction, urodynamic study has limitations as a biomarker, such as
      invasiveness and a lack of reproducibility of symptoms. Thus, many investigations
      about new biomarkers for lower urinary tract dysfunction have been carried out
      and reported. For imaging biomarkers, bladder and prostate parameters assessed by
      ultrasonography have been used to evaluate lower urinary tract dysfunction. For
      urinary biomarkers, neurotrophins, such as nerve growth factor and brain derived
      neurotrophics factor, prostaglandins and cytokines, have been analyzed and
      evaluated. Among these, nerve growth factor is considered one of the key factors
      in the pathophysiology of lower urinary tract dysfunction, and is researched in
      various ways. Serum markers have suggested that C-reactive protein and sex
      hormones have a relationship with lower urinary tract dysfunction. The
      possibility of genetic biomarkers in lower urinary tract dysfunction has also
      been raised. Nevertheless, as yet these biomarkers have not shown enough evidence
      to reflect lower urinary tract dysfunction and require further investigation.
      This review will discuss promising and potential biomarkers in lower urinary
      tract dysfunction to date.

PMID- 23113735
TI  - Colloidal graphene as a transducer in homogeneous fluorescence-based immunosensor
      for rapid and sensitive analysis of microcystin-LR.
AB  - Herein, we reported the assembly of colloidal graphene (CG) and microcystin (MC)
      LR-DNA bioconjugates to develop a homogeneous competitive fluorescence-based
      immunoassay for rapid and sensitive detection of MC-LR in water samples.
      Initially, the MC-LR-DNA probe was quickly adsorbed onto the CG surface through
      the strong noncovalent pi-pi stacking interactions and can be effectively
      quenched benefiting from the high quenching efficiency of CG. In contrast, the
      competitive binding of anti-MC-LR with MC-LR-DNA destroyed the graphene/MC-LR-DNA
      interaction, thus resulting in the restoration of fluorescence signal. This
      signal transduction mechanism made it possible for analysis of the target MC-LR.
      Taking advantage of the colloidal nature of the as-prepared graphene, the assay
      was carried out in homogeneous solution throughout, which avoided numerous
      immobilization, incubation, and washing steps that were necessary to traditional
      heterogeneous immunoassays, thereby reducing the whole assay time (within less
      than 35 min) and allowing a much better antigen-antibody interaction. Moreover,
      due to the direct competitive mode, the assay did not involve any antibody
      labeling or modification process, which would be beneficial to preserve the
      binding affinity of antigen-antibody. Under optimal conditions, the proposed
      immunosensor can be applied for quantitative analysis of MC-LR with a detection
      limit of 0.14 MUg/L, which satisfied the World Health Organization (WHO)
      provisional guideline limit of 1 MUg/L for MC-LR in drinking water, thus
      providing a powerful tool for rapid and sensitive monitoring of MC-LR in
      environmental samples.

PMID- 23113736
TI  - Dietary whey protein hydrolysates increase skeletal muscle glycogen levels via
      activation of glycogen synthase in mice.
AB  - Previously, we have shown that consuming carbohydrate plus whey protein
      hydrolysates (WPHs) replenished muscle glycogen after exercise more effectively
      than consuming intact whey protein or branched-chain amino acids (BCAAs). The
      mechanism leading to superior glycogen replenishment after consuming WPH is
      unclear. In this 5 week intervention, ddY mice were fed experimental diets
      containing WPH, a mixture of whey amino acids (WAAs), or casein (control). After
      the intervention, gastrocnemius muscle glycogen levels were significantly higher
      in the WPH group (4.35 mg/g) than in the WAA (3.15 mg/g) or control (2.51 mg/g)
      groups. In addition, total glycogen synthase (GS) protein levels were
      significantly higher in the WPH group (153%) than in the WAA (89.2%) or control
      groups, and phosphorylated GS levels were significantly decreased in the WPH
      group (51.4%). These results indicate that dietary WPH may increase the muscle
      glycogen content through increased GS activity.

PMID- 23113737
TI  - Structural and functional characterization of the Staphylococcus aureus virulence
      factor and vaccine candidate FhuD2.
AB  - Staphylococcus aureus is a human pathogen causing globally significant morbidity
      and mortality. The development of antibiotic resistance in S. aureus highlights
      the need for a preventive vaccine. In the present paper we explore the structure
      and function of FhuD2 (ferric-hydroxamate uptake D2), a staphylococcal surface
      lipoprotein mediating iron uptake during invasive infection, recently described
      as a promising vaccine candidate. Differential scanning fluorimetry and
      calorimetry studies revealed that FhuD2 is stabilized by hydroxamate
      siderophores. The FhuD2-ferrichrome interaction was of nanomolar affinity in
      surface plasmon resonance experiments and fully iron(III)-dependent. We
      determined the X-ray crystallographic structure of ligand-bound FhuD2 at 1.9 A (1
      A=0.1 nm) resolution, revealing the bilobate fold of class III SBPs (solute
      binding proteins). The ligand, ferrichrome, occupies a cleft between the FhuD2 N-
      and C-terminal lobes. Many FhuD2-siderophore interactions enable the specific
      recognition of ferrichrome. Biochemical data suggest that FhuD2 does not undergo
      significant conformational changes upon siderophore binding, supporting the
      hypothesis that the ligand-bound complex is essential for receptor engagement and
      uptake. Finally, immunizations with FhuD2 alone or FhuD2 formulated with
      hydroxamate siderophores were equally protective in a murine staphylococcal
      infection model, confirming the suitability and efficacy of apo-FhuD2 as a
      protective antigen, and suggesting that other class III SBPs might also be
      exploited as vaccine candidates.

PMID- 23113738
TI  - Synthesis of stereoisomers of Artemisia and Chrysanthemum bis(acetylenic) enol
      ether spiroacetals.
AB  - An 11-step synthesis is described of two diastereomeric candidates for a
      bis(acetylenic) enol ether spiroacetal isolated from Chrysanthemum boreale. Key
      steps in the synthetic route include spiroacetal lactone alkylidenation and
      subseqent modified Cadiot-Chodkiewicz cross-coupling to install the
      bis(acetylenic) enol ether functionality. From NMR comparisons, neither of the
      candidates, whose structures were confirmed by single-crystal X-ray diffraction,
      correspond to the natural product, and a proposal for the correct structure is
      put forward.

PMID- 23113739
TI  - What are we preparing them for? Development of an inventory of tasks for medical,
      surgical and supportive specialties.
AB  - BACKGROUND: Internationally, postgraduate medical education (PGME) has shifted to
      competency-based training. To evaluate the effects of this shift on the outcomes
      of PGME appropriate instruments are needed. AIM: To provide an inventory of tasks
      specialists perform in practice, which can be used as an instrument to evaluate
      the outcomes of PGME across disciplines. METHODS: Following methodology from job
      analysis in human resource management, we used document analyses, observations,
      interviews and questionnaires. Two thousand seven hundred and twenty eight
      specialists were then asked to indicate how frequently they performed each task
      in the inventory, and to suggest additional tasks. Face and content validity was
      evaluated using interviews and the questionnaire. Tasks with similar content were
      combined in a total of 12 clusters. Internal consistency was evaluated by
      calculating Cronbach's alpha. Construct validity was determined by examining
      predefined differences in task performance between medical, surgical and
      supportive disciplines. RESULTS: Seven hundred and six specialists (36%) returned
      the questionnaire. The resulting inventory of 91 tasks showed adequate face and
      content validity. Internal consistency of clusters of tasks was adequate.
      Significant differences in task performance between medical, surgical and
      supportive disciplines indicated construct validity. CONCLUSION: We established a
      comprehensive, generic and valid inventory of tasks of specialists which appears
      to be applicable across medical, surgical and supportive disciplines.

PMID- 23113740
TI  - Bioluminescent capsules for live-cell imaging.
AB  - A bioluminescent capsule was designed for illuminating cell signaling and protein
      localization. The capsule consists of four components, namely, a secretion
      peptide (SP), a luciferase body, a cargo protein (or peptide), and a membrane
      localization signal (MLS). Any functional proteins sandwiched between the
      luciferase body and MLS may be cartable to the plasma membrane (PM), where the
      capsule waits for outer signals and quickly releases the embedded luciferase in
      response to the signals. With this strategy of locating the capsule in the PM,
      the bioluminescence intensity was greatly prolonged and strengthened. A
      staurosporine (STS)-activated apoptosis signaling was efficiently imaged with the
      capsule carrying a DEVD peptide. Other functional proteins, such as fluorescent
      proteins and luciferases, were efficiently transported to the membrane by the
      capsule. A 60-nm-red-shifted bioluminescence was observed with a capsule fused
      with other luciferases or fluorescent proteins in living cells. This study gives
      a new insight regarding how to illuminate cellular signals with bioluminescence
      in living mammalian cells.

PMID- 23113742
TI  - What is the burden of living with autoimmune polyendocrinopathy candidiasis
      ectodermal dystrophy (APECED) in 2012? A health-related quality-of-life
      assessment in Finnish patients.
AB  - OBJECTIVE: Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy
      (APECED) is a rare disorder responsible for chronic candidiasis, a wide variety
      of autoimmune disorders and a risk of squamous cell carcinoma of the oral cavity
      or oesophagus. We investigated the impairment of quality of life in our cohort of
      Finnish patients. SUBJECTS, DESIGN AND MEASUREMENT: In a postal survey, 26
      patients with APECED responded to three self-reported health-related quality-of
      life questionnaires: RAND-36 (general health), RBDI (depression) and DLQI
      (dermatology life quality index). RESULTS: General health and vitality were the
      most affected items in our cohort. Male subjects presented higher impairment in
      emotional role limitations, social functioning, bodily pain, general mental
      health/emotional well-being, energy/vitality and general health perceptions but
      without reaching statistical significance. The number of accumulated diseases in
      APECED was not associated with lower results. But, age and duration of APECED
      correlated with fatigue (P = 0.01), well-being (P = 0.02) and general health (P =
      0.03) impairment. Depressive symptoms affected 29% of the patients. There was a
      statistical negative correlation between RBDI score and age and duration of
      APECED. Hair loss, alopecia areata universalis especially, affected more severely
      the quality of life of female patients. Vitiligo and candidiasis did not have any
      significant impact on both the genders. CONCLUSIONS: We report the first study on
      specific impairment of quality of life related to APECED in a cohort of adult
      Finnish patients. General health, emotional well-being and vitality were the most
      diminished aspects of quality of life in our cohort. However, our results will
      need to be confirmed by additional controlled studies.

PMID- 23113741
TI  - Differential requirements of CD4(+) T-cell signals for effector cytotoxic T
      lymphocyte (CTL) priming and functional memory CTL development at higher CD8(+) T
      cell precursor frequency.
AB  - Increased CD8(+) T-cell precursor frequency (PF) precludes the requirement of
      CD4(+) helper T (Th) cells for primary CD8(+) cytotoxic T-lymphocyte (CTL)
      responses. However, the key questions of whether unhelped CTLs generated at
      higher PF are functional effectors, and whether unhelped CTLs can differentiate
      into functional memory cells at higher PF are unclear. In this study, ovalbumin
      (OVA) -pulsed dendritic cells (DC(OVA)) derived from C57BL/6, CD40 knockout
      (CD40(-/-)) or CD40 ligand knockout (CD40L(-/-)) mice were used to immunize
      C57BL/6, Ia(b-/-), CD40(-/-) or CD40L(-/-) mice, whose PF was previously
      increased with transfer of 1 * 10(6) CD8(+) T cells derived from OVA-specific T
      cell receptor (TCR) transgenic OTI, OTI(CD40(-/-)) or OTI(CD40L(-/-)) mice. All
      the immunized mice were then assessed for effector and memory CTL responses.
      Following DC immunization, relatively comparable CTL priming occurred without
      CD4(+) T-cell help and Th-provided CD40/CD40L signalling. In addition, the
      unhelped CTLs were functional effectors capable of inducing therapeutic immunity
      against established OVA-expressing tumours. In contrast, the functional memory
      development of CTLs was severely impaired in the absence of CD4(+) T-cell help
      and CD40/CD40L signalling. Finally, unhelped memory CTLs failed to protect mice
      against lethal tumour challenge. Taken together, these results demonstrate that
      CD4(+) T-cell help at higher PF, is not required for effector CTL priming, but is
      required for functional memory CTL development against cancer. Our data may
      impact the development of novel preventive and therapeutic approaches in cancer
      patients with compromised CD4(+) T-cell functions.

PMID- 23113743
TI  - Impact of internalized stigma on HIV prevention behaviors among HIV-infected
      individuals seeking HIV care in Kenya.
AB  - In general, an initial diagnosis of HIV is likely to be correlated with the onset
      of HIV stigma. HIV-positive individuals are likely to internalize stigma, may
      suffer from psychosocial issues, or engage in maladaptive behaviors to cope with
      the diagnosis. Internalized stigma stems from fear of stigmatization also known
      as felt stigma. The current study examined the impact of HIV felt stigma on
      overall health and success of HIV prevention behaviors among 370 participants
      living with HIV and receiving care at an urban HIV clinic in Kenya. An 18-item
      instrument was cross culturally adapted to measure felt stigma. Descriptive and
      logistic regression analyses examined the data. Findings indicate that 25.9%
      (n=96) of participants who reported experiencing high levels of felt stigma
      related to other people's attitudes toward their condition, ostracizing, and a
      disruption of their personal life, were likely to not adhere to prescribed HIV
      medication and not disclose their HIV serostatus to one other person. Those who
      also experienced felt stigma related to a disruption of their personal lives
      while mediated by depression were likely to report poor overall health. Findings
      support having HIV clinics and interventions develop relevant HIV prevention
      strategies that focus on the emerging dimensions of felt stigma which can
      significantly impact disclosure of serostatus, medication adherence, and overall
      health.

PMID- 23113744
TI  - Congenital hypothyroidism with goiter in Tenterfield terriers.
AB  - BACKGROUND: A cluster of cases of congenital hypothyroidism with goiter (CHG) in
      Tenterfield Terriers was identified and hypothesized to be dyshormonogenesis of
      genetic etiology with autosomal recessive inheritance. OBJECTIVES: To describe
      the phenotype, thyroid histopathology, biochemistry, mode of inheritance, and
      causal mutation of CHG in Tenterfield Terriers. ANIMALS: Thyroid tissue from 1
      CHG-affected Tenterfield Terriers, 2 affected Toy Fox Terriers, and 7 normal
      control dogs. Genomic DNA from blood or buccal brushings of 114 additional
      Tenterfield Terriers. METHODS: Biochemical and genetic segregation analysis of
      functional gene candidates in a Tenterfield Terrier kindred. Thyroid peroxidase
      (TPO) iodide oxidation activity was measured, and TPO protein and SDS-resistant
      thyroglobulin aggregation were assessed on western blots. TPO cDNA was amplified
      from thyroid RNA and sequenced. Exons and flanking splice sites were amplified
      from genomic DNA and sequenced. Variant TPO allele segregation was assessed by
      restriction enzyme digestion of PCR products. RESULTS: Thyroid from an affected
      pup had lesions consistent with dyshormonogenesis. TPO activity was absent, but
      normal sized immunocrossreactive TPO protein was present. Affected dog cDNA and
      genomic sequences revealed a homozygous TPO missense mutation in exon 9 (R593W)
      that was heterozygous in all obligate carriers and in 31% of other clinically
      normal Tenterfield Terriers. CONCLUSIONS: The mutation underlying CHG in
      Tenterfield Terriers was identified, and a convenient carrier test made available
      for screening Tenterfield Terriers used for breeding.

PMID- 23113746
TI  - Coronal vertebral clefts: a radiological indicator for chromosomal aberrations.
AB  - Coronal clefts-a radiolucent band running through at least one vertebral body,
      visualized in the lateral spinal radiograph and discussed as a physiological
      variation of the fetal vertebral ossification pattern-are often found in fetal
      autopsies with trisomies. Published studies are missing concerning the question
      of whether this finding could serve as a diagnostic radiological or even
      ultrasonographic sign. We studied the incidence of radiological coronal clefts
      and their association with chromosomal aberrations in 443 fetuses (mostly
      medically induced abortions). In 42 of the 443 fetuses (9.5%), coronal clefts
      were visualized. The majority (71%) were localized in the lumbar spine. No
      cervical or singular sacral clefts were detected. Twenty-five of the 42 fetuses
      (60%) displaying coronal clefts had chromosomal aberrations, either as a trisomy
      (13 or 21) or as monosomy X. Histologically, coronal clefts showed a missing
      central ossification of the vertebral body. Remnants of the notochord could be
      excluded. Hence, coronal clefts represent a variant ossification of vertebral
      bodies in fetal development that is found almost exclusively in fetuses with
      chromosomal aberrations or severe congenital malformations. This finding could be
      a helpful supplement to prenatal diagnostics and fetal autopsy. On the other
      hand, the genetic diagnosis of chromosomal aberration, especially trisomy, does
      not automatically imply the presence of coronal clefts.

PMID- 23113747
TI  - Advanced glycation end products, measured as skin autofluorescence, during normal
      pregnancy and pregnancy complicated by diabetes mellitus.
AB  - BACKGROUND: Advanced glycation end products (AGEs) accumulate with age and in
      diabetes mellitus (DM). AGEs can be measured by the AGE Reader (DiagnOptics
      Technologies BV, Groningen, The Netherlands) using skin autofluorescence (SAF).
      SAF is related to chronic diabetes complications. In a previous study we reported
      that SAF is comparable in patients with gestational DM (GDM) and controls at 27
      weeks of gestation. In the current study we investigated SAF at multiple time
      points during pregnancy in pregnancies complicated by DM (type 1 or type 2) or
      GDM and in controls. Furthermore, the relation between SAF levels and adverse
      pregnancy outcomes was investigated. SUBJECTS AND METHODS: In this single-center
      prospective observational study SAF was measured during pregnancy from 26
      gestational weeks onward in 79 GDM patients, 21 patients with preexistent DM
      (type 1 or type 2), and 55 women without diabetes. Adverse pregnancy outcomes
      were recorded. RESULTS: SAF decreased slightly but significantly (beta = -0.018)
      during normal pregnancy but not in pregnancies complicated with hyperglycemia. At
      the end of pregnancy SAF was higher in patients with preexistent DM (1.91
      arbitrary [AU] units) compared with patients with GDM (1.71 AU) or normal
      pregnancy (1.66 AU) but did not differ between the latter two groups. SAF was not
      related to adverse pregnancy outcomes. CONCLUSIONS: The decrease in SAF during
      normal pregnancy could be the result of physiological changes. Because SAF was
      not related to adverse pregnancy outcomes, it is unlikely that the AGE Reader
      will be of use in daily clinical practice for GDM patients as a marker for
      identifying high-risk pregnancy outcomes.

PMID- 23113748
TI  - Crystalline polymorphs of [6,6]-phenyl-C61-butyric acid n-butyl ester (PCBNB).
AB  - The thermotropic behavior of [6,6]-phenyl-C(61)-butyric acid n-butyl ester
      (PCBNB) in powder and thin film form was investigated using X-ray diffraction and
      transmission electron microscopy. Upon heating PCBNB powder above its glass
      transition temperature, an amorphous-to-crystalline transition (i.e., cold
      crystallization) and a subsequent melting of these crystals were observed. A thin
      film of PCBNB was observed to order on a simple hexagonal lattice (HEX) with the
      c axis preferentially oriented normal to film at an annealing temperature of 180 
      degrees C but became disordered above 200  degrees C, consistent with the powder
      results. However, when annealed at 160  degrees C, the PCBNB thin film ordered on
      a superlattice of the HEX as indicated both by electron diffraction and high
      angle annular dark field scanning TEM (HAADF-STEM) images. The formation of the
      HEX superlattice polymorph was independent of both solvent and substrate and
      could be formed both on heating from the amorphous as cast state and by cooling
      from the HEX structure formed at a higher temperature. HAADF-STEM shows that the
      superlattice corresponds to a regular deficiency of PCBNB molecules on every
      fifth (1 1[combining overline] 0 0) plane of the HEX structure.

PMID- 23113749
TI  - Influences of multiple genetic polymorphisms on ovarian cancer risk in Malaysia.
AB  - OBJECTIVE: The identification of high-risk individuals can help to improve early
      cancer detection and patient survival. Risk assessment, however, can only be
      accomplished if the risk factors are known. To date, the genetic risk factors for
      ovarian cancer, other than mutations in the BRCA1/2 genes, have never been
      systematically explored in Malaysia. The present study aims to identify from a
      panel of cancer-associated single-nucleotide polymorphisms (SNPs), those
      associated with ovarian cancer risk in Malaysia. METHODS: A total of 768 SNPs
      associated with various cancers among Asians were identified through a search of
      the relevant literature, and these SNPs were then screened for their association
      with ovarian cancer. A total of 160 Malaysian subjects were recruited for the
      study, including both ovarian cancer patients and controls. Genotyping was
      carried out using Illumina BeadArray platform. RESULTS: A panel of 45 SNPs that
      are significantly (p<0.05) associated with ovarian cancer risk was identified.
      These ovarian cancer-associated SNPs were located in genes implicated in various
      pathways of carcinogenesis. Of these 45 SNPs, 5 have been previously associated
      with either ovarian cancer risk or survival. CONCLUSION: This study has
      identified a panel of 45 SNPs that are significantly associated with ovarian
      cancer in a Malaysian population.

PMID- 23113750
TI  - Spin accommodation and reactivity of silver clusters with oxygen: the enhanced
      stability of Ag13(-).
AB  - Spin accommodation is demonstrated to play a determining role in the reactivity
      of silver cluster anions with oxygen. Odd-electron silver clusters are found to
      be especially reactive, while the anionic 13-atom cluster exhibits unexpected
      stability against reactivity with oxygen. Theoretical studies show that the odd
      even selective behavior is correlated with the excitation needed to activate the
      O-O bond in O(2). Furthermore, by comparison with the reactivity of proximate
      even-electron clusters, we demonstrate that the inactivity of Ag(13)(-) is
      associated with its large spin excitation energy, ascribed to a crystal-field
      like splitting of the orbitals caused by the bilayer atomic structure, which
      induces a large gap despite not having a magic number of valence electrons.

PMID- 23113751
TI  - Low rate of pneumococci non-susceptible to penicillin in healthy Swedish
      toddlers.
AB  - BACKGROUND: Infection caused by Streptococcus pneumoniae is the leading cause of
      mortality in children worldwide. The aim of this study was to determine if a
      noted increase in non-susceptibility to penicillin among pneumococcal clinical
      isolates from young children reflected a similar increase in healthy children.
      METHODS: During 2004-2005, before the conjugate pneumococcal vaccine was
      introduced in Sweden, 663 healthy children (13-24 months of age) attending 17
      child health centres in Gothenburg, Sweden, were cultured for bacteria in the
      nasopharynx. Social factors were identified through a parental questionnaire.
      Pneumococcal serotypes and antibiotic resistance rates were determined.
      Antibiotic resistance was also monitored in 162 simultaneously obtained
      nasopharyngeal pneumococci isolated from clinical samples. RESULTS: The healthy
      children frequently carried pneumococci (45%), Moraxella catarrhalis (54%), and
      Haemophilus influenzae (22%). The carriage rates for all these pathogens were
      higher in children attending day care centres compared to children staying at
      home (p < 0.001). The dominating pneumococcal serotypes were 6B, 19F, 23F, and
      6A. Non-susceptibility to penicillin was low (4.0%) and only exceeded by that to
      trimethoprim-sulfamethoxazole (9.8%). Both rates were higher in the clinical
      isolates (9.3% and 16.7%, respectively; p < 0.05). No relationships to geographic
      area, day care attendance, recent antibiotic use, or travel abroad were shown for
      any specific serotype or for the presence of penicillin-non-susceptible
      pneumococci in the healthy children. CONCLUSIONS: Pneumococcal resistance rates
      in the healthy child population were low and did not reflect the higher rates
      noted at the laboratory in clinical samples obtained before and during the study.

PMID- 23113752
TI  - Phase II trial of sorafenib in patients with advanced anaplastic carcinoma of the
      thyroid.
AB  - BACKGROUND: Anaplastic thyroid cancer (ATC) is a rare but highly aggressive
      malignancy with a median survival of 3-5 months. The BRAF oncogene is mutated to
      its active form in up to 24% of ATC cases. Sorafenib is a tyrosine kinase
      inhibitor that acts on the RAF-1 serine/threonine kinase. In preclinical mouse
      models, sorafenib inhibits the growth of ATC xenografts and improves survival. No
      study of sorafenib in ATC has been conducted. We conducted a multi-institutional
      phase II trial of sorafenib in patients with ATC who had failed up to two
      previous therapies. METHODS: The primary endpoint of the trial was the Response
      Evaluation Criteria In Solid Tumors (RECIST)-defined imaging response rate.
      Twenty patients with ATC were treated with sorafenib 400 mg twice daily. RESULTS:
      Two of the 20 patients had a partial response (10%) and an additional 5 of 20
      (25%) had stable disease. The duration of response in the two responders was 10
      and 27 months, respectively. For the patients with stable disease, the median
      duration was 4 months (range 3-11 months). The overall median progression-free
      survival was 1.9 months with a median and a 1-year survival of 3.9 months and
      20%, respectively. Toxicity was manageable and as previously described for
      sorafenib, including hypertension and skin rash. CONCLUSION: Sorafenib has
      activity in ATC, but at a low frequency and similar to our previous experience
      with fosbretabulin. One patient with a response had previously progressed on
      fosbretabulin. Toxicities were both predictable and manageable.

PMID- 23113753
TI  - Presence of both heterogeneous vancomycin-intermediate resistance and beta-lactam
      antibiotic-induced vancomycin resistance phenotypes is associated with the
      outcome in methicillin-resistant Staphylococcus aureus bloodstream infection.
AB  - BACKGROUND: Although the individual expression of heterogeneous vancomycin
      intermediate resistance (hVISA) and beta-lactam antibiotic-induced vancomycin
      resistance (BIVR) phenotypes has been associated with treatment failure and
      recurrence in methicillin-resistant Staphylococcus aureus (MRSA) infections, the
      effect of the co-expression of these phenotypic profiles on clinical outcome has
      not been fully elucidated. The aim of this study was to determine the impact of
      the combination of hVISA and BIVR phenotypes on the clinical outcome in MRSA
      bacteremia. METHODS: One hundred and sixty-two MRSA blood isolates from a 21-y
      period, 1987-2007, were randomly selected. Screening for hVISA was done by the
      macromethod Etest and confirmed by population analysis profiles. BIVR was
      identified using Mu3 agar containing 4 MUg/ml of vancomycin. RESULTS: Thirty
      (18.5%) and 39 (24.1%) of the 162 MRSA blood isolates were positive for the hVISA
      and BIVR phenotypes, respectively. Eighteen (11.1%) isolates possessed both hVISA
      and BIVR phenotypes (hVISA(+)/BIVR(+)). In a subset of patients who received
      initial treatment with glycopeptides, only the patients whose isolates were
      hVISA(+)/BIVR(+) displayed a significantly higher mortality rate in comparison to
      those with non-hVISA(+)/BIVR(+) (80.0% vs 31.3%, p = 0.004). The presence of both
      hVISA and BIVR phenotypes was a predictor of mortality using a logistic
      regression analysis (p = 0.025). CONCLUSIONS: The combined phenotype of hVISA and
      BIVR was associated with a higher probability of mortality in patients with MRSA
      bacteremia. Further prospective studies are warranted to delineate the clinical
      significance of the combined phenotype of hVISA and BIVR.

PMID- 23113754
TI  - ADRB3 and PPARgamma2 gene polymorphisms and their association with cardiovascular
      disease risk in postmenopausal women.
AB  - OBJECTIVES: The contribution of heritability to the development of cardiovascular
      disease (CVD) is of interest as the identification of genes enhancing the
      susceptibility of individuals to CVD may help the design of clinical
      interventions optimized for the individual's genome. METHODS: We studied the
      associations of polymorphism of ADRB3 and PPARgamma2 genes with obesity indices,
      unfavorable lipid profile parameters and insulin resistance index HOMA in 343
      postmenopausal women. RESULTS: No association was found between tested
      polymorphisms and CVD risk factors such as total cholesterol >= 5.0 mmol/l, high
      density lipoprotein cholesterol < 1.2 mmol/l, low density lipoprotein cholesterol
      > 3.0 mmol/l and triacylglycerols > 1.7 mmol/l. The presence of arterial
      hypertension and HOMA value >= 1.95 were also not related to these polymorphisms.
      A significant association between PPARgamma2 gene polymorphism and total body fat
      mass (odds ratio = 1.90 at p = 0.037) as well as android fat deposit mass (odds
      ratio = 1.82 at p = 0.048) was found. CONCLUSIONS: CVD risk factors in
      postmenopausal women are not directly associated with the polymorphisms of
      PPARgamma2 and ADRB3 genes. We suggest that some indirect link between PPARgamma2
      gene polymorphism and susceptibility of postmenopausal women to CVD may exist.
      This suggestion is based on our finding that high total body fat mass and high
      android fat deposits are associated with the presence of the Pro12Ala allele of
      the PPARgamma2 gene.

PMID- 23113755
TI  - Siliconized triarylamines as redox mediator in dye-sensitized solar cells.
AB  - A new class of triarylamine compound functionalized with bulky triisopropylsilyl
      ether (-OTIPS) groups is used as a hole transport material in dye-sensitized
      solar cells (DSSCs). Using both optical and photoelectrochemical techniques, we
      compared the performance of this compound with that of a parent compound
      containing methyl ethers as well as the conventional I3-/I- redox couple. DSSCs
      fabricated with the triisopropylsilyl ether-substituted triarylamine exhibited
      high open circuit potentials (V(oc) > 0.9 V on average) and efficiencies of up to
      1.9%. However, cells fabricated with triarylamine containing methyl ethers
      performed very poorly, pointing to the importance of -OTIPS in the overall
      performance of this material.

PMID- 23113756
TI  - Patient satisfaction with out-of-hours GP cooperatives: a longitudinal study.
AB  - OBJECTIVE: For over a decade, out-of-hours primary care in the Netherlands has
      been provided by general practitioner (GP) cooperatives. In the past years,
      quality improvements have been made and patients have become acquainted with the
      service. This may have increased patient satisfaction. The objective of this
      study was to examine changes in patient satisfaction with GP cooperatives over
      time. DESIGN: Longitudinal observational study. A validated patient satisfaction
      questionnaire was distributed in 2003-2004 (T1) and 2007-2008 (T2). Items were
      rated on a scale from 0 to 10 (1 = very bad; 10 = excellent). SETTING: Eight GP
      cooperatives in the Netherlands. SUBJECTS: Stratified sample of 9600 patients.
      Response was 55% at T1 (n = 2634) and 51% at T2 (n = 2462). MAIN OUTCOME
      MEASURES: Expectations met; satisfaction with triage nurses, GPs, and
      organization. RESULTS: For most patients the care received at the GP cooperative
      met their expectations (T1: 86.1% and T2: 88.4%). Patients were satisfied with
      the triage nurses (overall grade T1: 7.73 and T2: 7.99), GPs (T1: 8.04 and T2:
      8.25), and organization (overall grade T1: 7.60 and T2: 7.78). Satisfaction with
      triage nurses showed the largest increase over time. The quality and
      effectiveness of advice or treatment were given relatively low grades. Of all
      organizational aspects, the lowest grades were given for waiting times and
      information about the cooperative. CONCLUSION: In general, patients were
      initially satisfied with GP cooperatives and satisfaction had even increased four
      years later. However, there is room for improvement in the content of the advice,
      waiting times, and information supply. More research is needed into satisfaction
      of specific patient groups.

PMID- 23113757
TI  - Implementation intentions intervention among temporarily deferred novice blood
      donors.
AB  - BACKGROUND: Approximately 12% to 15% of blood donors are temporarily deferred
      from giving blood because they fail relevant medical criteria. Temporary deferral
      has a profound negative impact on subsequent donation. To our knowledge, an
      implementation intentions intervention has never been tested among temporarily
      deferred donors. We hypothesized that return rates would be higher among
      participants exposed to an implementation intentions intervention compared to
      those in a control condition that is mere measurement of related cognitions.
      STUDY DESIGN AND METHODS: Participants were assigned to implementation intentions
      or mere measurement conditions; whether or not participants received a temporary
      interdiction on giving blood was measured. A total of 956 novice donors were
      temporarily deferred (n = 490, in the implementation intentions condition; n =
      466, in the mere measurement condition). Participants in the implementation
      intentions condition formed if-then plans to overcome three common barriers to
      blood donation: forgetting to attend, fitting the opportunity to give blood into
      one's schedule, and organizing transportation to the donation venue. Participants
      in the mere measurement condition did not form plans. RESULTS: Participants in
      the implementation intentions condition had a 19% greater chance of returning to
      give blood again within the 4 years after their first lifetime donation compared
      to participants in the mere measurement condition (p = 0.04) when controlling for
      sex and attempt at which participants were deferred. CONCLUSION: The results of
      this study indicate that implementation intentions could be a useful strategy for
      promoting donor return among temporarily deferred novice blood donors.

PMID- 23113758
TI  - Adult-onset verrucous nevus lipomatosus cutaneous superficialis.

PMID- 23113759
TI  - Effect of long-term freezing and freeze-thaw cycles on indigenous and inoculated
      microorganisms in dewatered blackwater.
AB  - Wastewater treatment in many Arctic regions is inadequate, even nonexisting.
      Natural freezing of wastewater in those areas may be beneficial for reduction of
      microorganisms. The aim of this study was to investigate the effect of long-term
      freezing, and repeated freezing and thawing, on indigenous coliforms, fecal
      streptococci, and antibiotic-resistant (AR) bacteria, and inoculated Salmonella
      Enteriditis and E. coli bacteriophage PhiX174 in dewatered blackwater. At the end
      of the long-term freezing experiment (10 months), an MPN recovery study was done,
      including the microbial groups that had shown the largest reduction, using
      tryptone soy broth at incubation temperatures of 10 and 20  degrees C overnight
      for the coliforms and AR bacteria, and buffered peptone water at incubation
      temperature of 37  degrees C for 18-20 h for Salmonella. Fecal streptococci were
      more resistant to long-term freezing than the coliform group. Total number of AR
      bacteria decreased slowly but constantly over the 10-month freezing period.
      Salmonella rapidly decreased and were nondetectable within a week but exhibited
      some recovery after 10 months of freezing, whereas limited or no recovery of
      coliforms and AR-bacteria was detected. Bacteriophages showed limited reduction
      during the long-term freezing. Repeated freezing and thawing increased the
      reduction of all tested microbial groups markedly.

PMID- 23113760
TI  - Ribonucleotide reductase small subunit M2 serves as a prognostic biomarker and
      predicts poor survival of colorectal cancers.
AB  - The overexpression of RRM2 [RR (ribonucleotide reductase) small subunit M2]
      dramatically enhances the ability of the cancer cell to proliferate and to
      invade. To investigate further the relevance of RRM2 and CRCs (colorectal
      cancers), we correlated the expression of RRM2 with the clinical outcome of CRCs.
      A retrospective outcome study was conducted on CRCs collected from the COH [(City
      of Hope) National Medical Center, 217 cases] and ZJU (Zhejiang University, 220
      cases). IHC (immunohistochemistry) was employed to determine the protein
      expression level of RRM2, and quantitative real-time PCR was employed to
      validate. Multivariate logistic analysis indicated that the adjusted ORs (odds
      ratios) of RRM2-high for distant metastases were 2.06 [95% CI (confidence
      interval), 1.01-4.30] and 5.89 (95% CI, 1.51-39.13) in the COH and ZJU sets
      respectively. The Kaplan-Meier analysis displayed that high expression of RRM2
      had a negative impact on the OS (overall survival) and PFS (progress-free
      survival) of CRC in both sets significantly. The multivariate Cox analysis
      further demonstrated that HRs (hazard ratios) of RRM2-high for OS were 1.88 (95%
      CI, 1.03-3.36) and 2.06 (95% CI, 1.10-4.00) in the COH and ZJU sets respectively.
      Stratification analysis demonstrated that the HR of RRM2 dramatically increased
      to 12.22 (95% CI, 1.62-258.31) in the MMR (mismatch repair) gene-deficient
      subgroup in the COH set. Meanwhile, a real-time study demonstrated that down
      regulation of RRM2 by siRNA (small interfering RNA) could significantly and
      specifically reduce the cell growth and adhesion ability in HT-29 and HCT-8
      cells. Therefore RRM2 is an independent prognostic factor and predicts poor
      survival of CRCs. It is also a potential predictor for identifying good
      responders to chemotherapy for CRCs.

PMID- 23113761
TI  - Editorial Comment to Potential tumor markers of renal cell carcinoma: alpha
      enolase for postoperative follow up, and galectin-1 and galectin-3 for primary
      detection.

PMID- 23113762
TI  - Three-dimensionally engineered porous silicon electrodes for Li ion batteries.
AB  - The ultimate goal of Li ion battery design should consist of fully accessible
      metallic current collectors, possibly of nanoscale dimensions, intimately in
      contact with high capacity stable electrode materials. Here we engineer three
      dimensional porous nickel based current collector coated conformally with layers
      of silicon, which typically suffers from poor cycle life, to form high-capacity
      electrodes. These binder/conductive additive free silicon electrodes show
      excellent electrode adhesion resulting in superior cyclic stability and rate
      capability. The nickel current collector design also allows for an increase in
      silicon loading per unit area leading to high areal discharge capacities of up to
      0.8 mAh/cm(2) without significant loss in rate capability. An excellent electrode
      utilization (~85%) and improved cyclic stability for the metal/silicon system is
      attributed to reduced internal stresses/fracture upon electrode expansion during
      cycling and shorter ionic/electronic diffusion pathways that help in improving
      the rate capability of thicker silicon layers.

PMID- 23113763
TI  - Chemopreventive effects of pterostilbene on urethane-induced lung carcinogenesis
      in mice via the inhibition of EGFR-mediated pathways and the induction of
      apoptosis and autophagy.
AB  - Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer
      deaths globally. Due to the lack of successful chemopreventive agents for lung
      cancer, there is an emerging need to evaluate new and effective agents for lung
      cancer prevention. Pterostilbene, a naturally occurring analogue of resveratrol,
      has been reported to be an effective chemopreventive agent against many cancers.
      The aim of this study is to investigate the chemopreventive effects of
      pterostilbene in urethane-induced murine lung tumors. Pretreatment with
      pterostilbene at 50 or 250 mg/kg significantly reduced tumor multiplicity by 26
      and 49%, respectively. Pterostilbene also significantly inhibited tumor volume by
      25 and 34% and decreased the tumor burden per mouse by 45 and 63%, respectively.
      The mechanisms by which pterostilbene suppresses lung tumorigenesis have been
      investigated in lung tissues and homogenates. The results indicate that the
      pterostilbene-mediated chemopreventive effects in vivo were a result of the
      inhibition of epidermal growth factor receptor (EGFR) and its downstream
      pathways, leading to retarded cell cycle progression, and of the induction of
      apoptosis and autophagy during urethane-induced lung tumorigenesis.

PMID- 23113764
TI  - Diastereoselective multicomponent cascade reaction leading to [3.2.0]
      heterobicyclic compounds.
AB  - A general three-component triple cascade reaction through an iminium-enamine
      iminium sequential activation initiated by a hetero-Michael addition to
      alpha,beta-unsaturated aldehydes affords [3.2.0]heterobicycles in high
      diastereoselectivity. The rate and diastereoselectivity of the reaction depended
      on the (E)-4-heterocrotonate and size of the secondary amine. The enantiomers of
      the major diastereoisomer of oxa- and azabicyclo[3.2.0]heptane derivatives were
      separated by enzymatic kinetic resolution with immobilized  Candida antarctica 
      Lipase B (CALB), with E values up to 153. The absolute configuration of the
      nonacylated enantiomer of oxabicyclo[3.2.0]heptane was determined by single
      crystal X-ray analysis.

PMID- 23113765
TI  - Fluorogenic RNA nanoparticles for monitoring RNA folding and degradation in real
      time in living cells.
AB  - Due to the discovery of more and more roles of cellular noncoding RNAs, the
      approaches for introducing RNAs including small interfering RNA (siRNA), micro
      RNA (miRNA), ribozyme, and riboswitch into cells for regulating cell life cycle
      and for the treatment of diseases have become routine practice. The understanding
      of RNA folding, degradation, and intracellular half-life after entering the cell
      is an intriguing question in biology and pharmacology. Currently, methods to
      detect RNA folding, degradation, and half-life in real time within the cell is
      extremely challenging. The common assay method to measure RNA half-life and
      degradation in vivo is the use of radioactive markers or fluorescence RNA
      labeling. The challenge is, after RNA becomes degraded or misfolded, the isotope
      or the fluorescence is still present in the cell, thus the signals are not a true
      indication of the presence of the RNA in the cell. The alternate method commonly
      used to measure RNA life is to isolate RNA from cells and distinguish between
      intact and degraded RNA by gel, chromatography, or capillary electrophoresis.
      However, when a cell is breaking down, ribonucleases (RNases) will be released
      from cell compartments, and degradation of small RNA in cell lysates occurs
      immediately after cell lysis. Here we report a method to monitor RNA degradation
      in real time in living cells using fluorogenic RNA in combination with RNA
      nanotechnology (Guo, 2010; Guo et al., 2012). The RNA aptamer that binds
      malachite green (MG), the ribozyme that cleaves the hepatitis virus genome, and a
      siRNA for firefly luciferase were all fused to the bacteriophage phi29 packaging
      RNA (pRNA) 3-way junction (3WJ) motif to generate RNA nanoparticles. The MG
      aptamer, the hepatitis B virus ribozyme, and the luciferase siRNA all retained
      their function independently after fusion into the nanoparticles. When the RNA
      nanoparticle is degraded, denatured, or misfolded, the fluorescence disappears.
      MG, which is not fluorescent by itself, is capable of binding to its aptamer and
      emitting fluorescent light only if the RNA remains folded in the correct
      conformation. Therefore, the MG aptamer fluorescence (in the presence of MG dye)
      can be used as a measure of the degradation and folding of RNA nanoparticles, the
      siRNA, the aptamer, and the ribozyme in the cell in real time using
      epifluorescence microscopy and fluorescence spectroscopy without lysing the
      cells. We show that the half-life (t1/2) of the electroporated MG aptamer
      containing RNA nanoparticle was 4.3 hours after electroporation into cells.

PMID- 23113766
TI  - Identification and characterization of an agonistic aptamer against the T cell
      costimulatory receptor, OX40.
AB  - Induction of an effective immune response that can target and eliminate malignant
      cells or virus-infected cells requires the stimulation of antigen-specific
      effector T cells. A productive and long-lasting memory response requires 2
      signals: a specific signal provided by antigen recognition through engagement of
      the T cell receptor and a secondary signal via engagement of costimulatory
      molecules (such as OX40) on these newly activated T cells. The OX40-OX40-ligand
      interaction is critical for the generation of productive effector and memory T
      cell functions. Thus agonistic antibodies that stimulate OX40 on activated T
      cells have been used as adjuvants to augment immune responses. We previously
      demonstrated that an aptamer modified to stimulate murine OX40 enhanced vaccine
      mediated immune responses in a murine melanoma model. In this study, we describe
      the development of an agonistic aptamer that targets human OX40 (hOX40). This
      hOX40 aptamer was isolated using systematic evolution of ligands by exponential
      enrichment and binds the target purified protein with high affinity [dissociation
      constants (K(d))<10 nM]. Moreover, the hOX40 aptamer-streptavidin complex has an
      apparent binding affinity of ~50 nM for hOX40 on activated T cells as determined
      by flow cytometry and specifically binds activated human T cells. A multivalent
      version of the aptamer, but not a mutant version of the aptamer, was able to
      stimulate OX40 on T cells and enhance cell proliferation and interferon-gamma
      production. Future studies will assess the therapeutic potential of hOX40
      aptamers for ex vivo stimulation of antigen specific T cells in conjunction with
      dendritic cell-based vaccines for adoptive cellular therapy.

PMID- 23113767
TI  - Nucleic acid aptamers against biotoxins: a new paradigm toward the treatment and
      diagnostic approach.
AB  - Nucleic acid aptamers are short single-stranded DNA or RNA oligonucleotides that
      can bind to their targets with very high affinity and specificity, and are
      generally selected by a process referred to as systematic evolution of ligands by
      exponential enrichment. Conventional antibody-based therapeutic and diagnostic
      approach currently employed against biotoxins pose major limitations such as the
      requirement of a live animal for the in vivo enrichment of the antibody species,
      decreased stability, high production cost, and side effects. Aptamer technology
      is a viable alternative that can be used to combat these problems. Fully
      sequestered in vitro, aptamers eliminate the need for a living host. Furthermore,
      one of the key advantages of using aptamers instead of antibodies is that they
      can be selected against very weakly immunogenic and cytotoxic substances. In this
      review, we focus on nucleic acid aptamers developed against various biotoxins of
      plant, microorganism, or animal origin and show how these can be used in
      diagnostics (e.g., biosensors) and therapy.

PMID- 23113769
TI  - Hyaluronic acid immobilized polyacrylamide nanoparticle sensors for CD44 receptor
      targeting and pH measurement in cells.
AB  - Our ability to design receptor-targeted nanocarriers aimed at drug release after
      endocytosis is limited by the current knowledge of intracellular nanoparticle
      (NP) trafficking. It is not clear if NP size, surface chemistry, and/or targeting
      of cell surface receptors changes the intracellular fate of NPs; i.e., will all
      NPs enter acidic compartments and eventually end up in lysosomes or are there
      escape mechanisms or receptor-specific signaling that can be induced to change
      the cellular processing of an internalized NP? To give new insight into the
      intracellular trafficking of NPs that target the CD44 receptor, which is
      overexpressed on the surface of a broad variety of cancer cells, we have
      synthesized an NP pH sensor system that targets CD44. We used a polyacrylamide
      nanoparticle matrix bearing hyaluronic acid (HA) on the surface as a CD44
      targeting ligand. The HA-coated NPs were prepared by radical polymerization
      followed by post functionalization with sensor fluorophores and physically
      absorbed or chemically conjugated HA. Cell uptake studies showed significant
      uptake of HA-coated nanosensors in HeLa cells and no uptake under the same
      conditions without the HA targeting ligand. The pH distribution profile in cells
      was measured for nanosensors with HA, cationic, and noncharged NP surface
      coatings giving a clear indication of the intracellular pH environment that the
      different NPs experience after internalization. The pH profile of cationic
      nanosensors in comparison to HA conjugated nanosensors indicates that the
      intracellular trafficking is aimed at lysosomes regardless of whether CD44
      receptor-specific or unspecific uptake is induced.

PMID- 23113771
TI  - Neonatal alloimmune thrombocytopenia associated with massive chronic
      intervillositis: a case report and review of the literature.
AB  - Neonatal alloimmune thrombocytopenia (NAIT) presents as isolated thrombocytopenia
      in a normal neonate as a result of destruction of fetal platelets by maternal
      antibodies against paternally derived human platelet antigens. Neonatal
      alloimmune thrombocytopenia affects 0.1% of births, with maternal antibodies
      crossing the placenta as early as 14 weeks' gestation. Few reports describe
      placental histopathological changes occurring in NAIT cases. We present a case of
      NAIT associated with massive chronic intervillositis, a rare entity occurring in
      0.06% to 0.8% of reviewed 2nd- and 3rd-trimester placentas; to our knowledge,
      this is the 1st report of such an association.

PMID- 23113772
TI  - Radial and longitudinal strain and strain rate assessed by speckle-tracking
      echocardiography in dogs with myxomatous mitral valve disease.
AB  - BACKGROUND: Assessment of left ventricular (LV) function using conventional
      echocardiographic methods is difficult in mitral regurgitation (MR) owing to
      altered hemodynamic loading conditions. Newer methods such as speckle-tracking
      echocardiography (STE) provide assessment of LV strain (St) and strain rates
      (SR). HYPOTHESES: Global St and SR are 1) decreased in dogs with clinical signs
      of congestive heart failure (CHF) due to myxomatous mitral valve disease (MMVD)
      compared with clinically healthy dogs, and are 2) associated with conventional
      echocardiographic indices of MMVD severity. ANIMALS: The study subjects were 93
      privately owned dogs with different MMVD severities. METHODS: Prospectively
      recruited dogs were grouped according to MMVD severity based on echocardiographic
      evaluation of MR and presence of clinical signs. Global radial and longitudinal
      St, SR, and indices of LV dyssynchrony were assessed. RESULTS: On group-wise
      comparisons, dogs with CHF had increased global longitudinal St, global
      longitudinal and radial SR in systole (SRs), and early diastole (SRe) compared
      with dogs with no or minimal MR (all P < .04). On multiple regression analyses,
      these global STE variables increased with degree of MR, but associations with
      left atrial-to-aortic root ratio (LA/Ao) were best described by second-order
      polynomial equations. Thus, curvilinear relationships were found for LA/Ao and
      longitudinal St, SRs, and SRe (all P < .002) and radial St and SRe (all P <
      .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Assessed by STE, LV function appeared
      to be augmented in moderate-to-severe disease. However, at CHF stages with
      greatly enlarged atria, a decrease to levels comparable to dogs with no or
      minimal MR was observed.

PMID- 23113773
TI  - Risk factors and outcomes in patients with carbapenem-resistant Acinetobacter
      infection.
AB  - INTRODUCTION: Acinetobacter spp. are important pathogens increasingly reported as
      the cause of outbreaks of nosocomial infections. The aim of our study was to
      identify the risk factors and assess their influence on outcomes in patients with
      infections caused by carbapenem-resistant Acinetobacter spp. METHODS: A
      retrospective data analysis was performed to evaluate risk factors and mortality
      in patients with Acinetobacter spp. infections. Methods used for the statistical
      analysis were the Student's t-test, Chi-square test, and multivariate analysis; p
      < 0.05 was considered statistically significant. RESULTS: A total of 99 patients
      with an Acinetobacter spp. infection were identified. Comparing patients with
      carbapenem-sensitive and carbapenem-resistant Acinetobacter spp. infection,
      significant differences were found in the mean length of intensive care unit stay
      (4.17 +/- 3.61 vs 7.92 +/- 6.74 days, p = 0.038) and mechanical ventilation (3.25
      +/- 2.61 and 7.07 +/- 5.79 days, p = 0.009). The previous use of carbapenems
      (odds ratio (OR) 10.1, 95% confidence interval (CI) 1.16-87.20) and
      fluoroquinolones (OR 3.6, 95% CI 1.13-11.51) was independently associated with
      resistance to carbapenems. Of the Acinetobacter spp. strains, 94.9% (n = 94) were
      resistant to piperacillin-tazobactam, 88.9% (n = 88) to ceftazidime, 85.9% (n =
      85) to ciprofloxacin, 83.8% (n = 83) to gentamicin, 79.8 (n = 79) to amikacin,
      and 48.5% (n = 48) to cefepime. CONCLUSIONS: Intensive care unit stay before
      infection and source of infection in the respiratory tract were independently
      associated with patient mortality. Resistance to carbapenems had no impact on
      mortality rates. Carbapenem-resistant Acinetobacter spp. isolates had high
      resistance rates to other antimicrobial drugs.

PMID- 23113774
TI  - Rebranding exercise: there's an app for that.
AB  - Historically, the approach of promoting exercise by emphasizing its effects on
      long-term health has predominated. Despite this tradition, there is no strong
      empirical support for such an approach. Recent work has argued that exercise
      suffers from a "branding problem" and efforts to promote exercise may be better
      served by switching the focus from the long-term benefits of exercise that
      improve health, to the immediate benefits of exercise that enhance quality of
      life. One way to disseminate and reinforce this message could be through a
      smartphone application designed to monitor daily improvements on quality of life
      constructs correlated with exercise participation.

PMID- 23113775
TI  - Physician counseling of older adults about physical activity: the importance of
      context.
AB  - PURPOSE: Physicians are encouraged to discuss physical activity with their older
      adult patients. Studies of physician-initiated counseling have yielded
      inconsistent results, perhaps because older adults' perceptions and concerns
      about such counseling have not been addressed. The objective of the present work
      was therefore to explore such perceptions and their implications. DESIGN:
      Qualitative study, using a grounded theory approach. Data were collected using
      both focus groups and semistructured interviews. SETTING: Data were collected in
      several settings, including a fitness center and physicians' offices. SUBJECTS:
      In a first sample, 56 adults aged 65 and older participated in one of six focus
      group sessions examining physical activity and exercise. Subsequently, 16 older
      adults participated in one of two focus groups comprising a second, validation
      sample. Individual semistructured interviews were conducted with a sample of five
      physicians. METHODS: Data collection and analysis took place concurrently.
      Transcripts were analyzed using the constant comparative method. Recruitment,
      data collection, and analysis were informed by grounded theory. RESULTS: Inactive
      older adults experiencing a health problem were more receptive than their healthy
      counterparts to receiving physical activity counseling from their physicians.
      Those who were receptive appeared to find such an intervention useful in leading
      to behavior change. CONCLUSION: This study suggests that physicians' efforts in
      physical activity counseling may have the best impact when provided in the
      context of a health problem.

PMID- 23113776
TI  - Effects of a novel school-based cross-curricular physical activity intervention
      on cardiovascular disease risk factors in 11- to 14-year-olds: the activity
      knowledge circuit.
AB  - PURPOSE: This study investigates cardiovascular disease risk factor response in
      adolescents following introduction of brisk walking into curriculum lessons.
      DESIGN: Quasi-experimental. SETTING: School-based. SUBJECTS: An intervention
      group consisted of 115 (aged 12.4 +/- 0.5 y) year eight participants, and 77
      (aged 12.1 +/- 1.1 y) year seven and year nine participants formed a control.
      INTERVENTION: An 18-week cross-curricular physical activity intervention was
      implemented in one secondary school. MEASURES: Adiposity variables, blood
      pressure, lipids, lipoproteins, glucose, insulin, high-sensitivity C-reactive
      protein, high-molecular-weight adiponectin, aerobic fitness, physical activity
      behavior, and diet were assessed preintervention and postintervention. ANALYSIS:
      Dependent and independent t-tests. RESULTS: Prevalence of elevated waist
      circumference (9.8% vs. 6.9%), systolic blood pressure (3.3% vs. 0%),
      triglycerides (2.5% vs. 1.2%), and reduced high density lipoprotein cholesterol
      (3.7% vs. 2.7%) decreased in the intervention group. Significant improvements in
      high density lipoprotein cholesterol to total cholesterol ratio (mean +/- SD: 2%
      +/- 4% [confidence interval (CI)(0.05)  =  1% to 2%], t(80)  =  -3.5, p  =  .001)
      and glucose (-.1 +/- .4 mmol/L [CI(0.05)  =  -.2% to 0%], t(79)  =  3.2, p  = 
      .002) were evident for the intervention group. CONCLUSION: The Activity Knowledge
      Circuit may prove to be a sustainable, effective, and cost-effective strategy to
      engage schoolchildren in physical activity on a daily basis. A longer-duration
      intervention is required to fully understand risk factor response in adolescents.

PMID- 23113777
TI  - Caregiver burden and nonachievement of healthy lifestyle behaviors among family
      caregivers of cardiovascular disease patients.
AB  - PURPOSE: To determine whether caregiver burdens are associated with lifestyle
      behaviors 1 year following the hospitalization of a family member with
      cardiovascular disease (CVD). DESIGN: Prospective follow-up study of National
      Heart Lung and Blood Institute sponsored Family Intervention Trial for Heart
      Health participants. SETTING: Hospital-based recruitment/baseline visit with 1
      year follow-up. SUBJECTS: Family members of hospitalized CVD patients (N  =  423;
      67% female; 36% racial/ethnic minority; mean age 49 years). MEASURES: Systematic
      evaluation at 1 year to determine heart-healthy diet (defined as <10% kcal from
      saturated fat; Block 98 Food Frequency Questionnaire) and physical activity
      (defined as >=4 d/wk; Behavioral Risk Factor Surveillance System Survey)
      behaviors and caregiver burdens (five domains: employment, financial, physical,
      social, and time; Caregiver Strain Questionnaire). ANALYSIS: Logistic regression
      adjusted for covariates. RESULTS: Heart-healthy diet was less frequent among
      caregivers citing feeling overwhelmed (odds ratio [OR]  =  .50; 95% confidence
      interval [CI]  =  .26-.97), sleep disturbance (OR  =  .51; 95% CI  =  .27-.96),
      financial strain (OR  =  .41; 95% CI  =  .20-.86), upsetting behavior (OR  = 
      .48; 95% CI  =  .25-.92), and/or time demands (OR  =  .47; 95% CI  =  .26-.85) as
      burdens. Physical activity was less frequent among caregivers reporting financial
      strain (OR  =  .32; 95% CI  =  .13-.81) or upsetting patient behavior (OR  = 
      .33; 95% CI  =  .15-.76) as burdens. The most commonly cited caregiver burdens
      included changes in personal plans (39%), time demands (38%), and sleep
      disturbance (30%). CONCLUSION: Caregiver burdens were associated with
      nonachievement of heart-healthy diet and physical activity behaviors among family
      caregivers 1 year after patient discharge. When developing heart-health promotion
      interventions, caregiver burden should be considered as a possible barrier to
      prevention among family members of CVD patients.

PMID- 23113778
TI  - Homeless former smokers' interest in helping homeless current smokers quit.
AB  - PURPOSE: To describe the factors associated with interest of homeless former
      smokers in helping homeless smokers quit. METHODS: A cross-sectional survey
      administered to an optimized convenience sample of homeless persons (n  =  4570)
      at emergency shelters, transitional housing units, and open encampments in 80
      cities across Minnesota. The in-person survey response rate was 90%. ANALYSIS:
      Chi-square tests and t-tests for univariate analysis. RESULTS: Of 4534
      participants completing the smoking questions, 546 participants (12%) self
      identified as former smokers, of which 59% expressed interest in helping homeless
      smokers quit. Significant predictors of reported interest in helping included
      racial/ethnic background (p < .05), number of people known who had quit smoking
      (p < .01), and receiving social services as an adult (p < .01). CONCLUSION:
      Homeless former smokers are a potential resource for peer support programs to
      promote smoking cessation among homeless current smokers.

PMID- 23113779
TI  - Addressing weight gain in smoking cessation treatment: a randomized controlled
      trial.
AB  - PURPOSE: To evaluate the effectiveness of a cognitive behavioral treatment (CBT)
      addressing cessation-related weight concerns delivered via a tobacco quitline
      that does not address weight concerns. DESIGN: Randomized controlled trial,
      blinded 6-month follow-up. SETTING: The Oklahoma Tobacco Helpline (OKHL).
      SUBJECTS: All 7998 smokers who called the OKHL were screened; 4240 were eligible;
      2000 were randomized to the standard quitline (STD) or the brief version of the
      CBT weight concerns program (WCP). INTERVENTION: Telephone counseling to help
      people quit smoking and address concerns about cessation-related weight gain.
      MEASURES: Demographics, weight, tobacco status, weight concerns, self-efficacy in
      quitting, and quitting without weight gain. ANALYSIS: Descriptive statistics and
      logistic regression. RESULTS: Of those randomized, 1002 participants completed
      the 6-month survey (response rates  =  53.2% for STD, 47% for WCP). Compared with
      STD, WCP led to reduced weight concerns (p < .01) and less weight gain among
      quitters (1.8 vs. -3.4 pounds; p  =  .01). Although not significant, participants
      in the WCP were more likely to report 30-day abstinence (33.3% vs. 36.8%, p  = 
      .24; intent to treat  =  17.7 vs. 17.3). CONCLUSION: The WCP was successfully
      delivered via a quitline and resulted in improved attitudes about weight and
      decreased cessation-related weight gain without harming quit rates. Promotion of
      a quitline focused on addressing weight in conjunction with quitline treatment
      for smoking cessation may improve cessation and weight outcomes. Study
      limitations include use of self-report and survey response.

PMID- 23113780
TI  - Stakeholder perspectives on workplace health promotion: a qualitative study of
      midsized employers in low-wage industries.
AB  - PURPOSE: Study goals were to (1) describe stakeholder perceptions of workplace
      health promotion (WHP) appropriateness, (2) describe barriers and facilitators to
      implementing WHP, (3) learn the extent to which WHP programs are offered to
      workers' spouses and partners and assess attitudes toward including partners in
      WHP programs, and (4) describe willingness to collaborate with nonprofit agencies
      to offer WHP. DESIGN: Five 1.5-hour focus groups. SETTING: The focus groups were
      conducted with representatives of midsized (100-999 workers) workplaces in the
      Seattle metropolitan area, Washington state. SUBJECTS: Thirty-four human
      resources professionals in charge of WHP programs and policies from five low-wage
      industries: accommodation/food services, manufacturing, health care/social
      assistance, education, and retail trade. MEASURES: A semistructured discussion
      guide. ANALYSIS: Qualitative analysis of focus group transcripts using grounded
      theory to identify themes. RESULTS: Most participants viewed WHP as appropriate,
      but many expressed reservations about intruding in workers' personal lives.
      Barriers to implementing WHP included cost, time, logistical challenges, and
      unsupportive culture. Participants saw value in extending WHP programs to
      workers' partners, but were unsure how to do so. Most were willing to work with
      nonprofit agencies to offer WHP. CONCLUSION: Midsized, low-wage employers face
      significant barriers to implementing WHP; to reach these employers and their
      workers, nonprofit agencies and WHP vendors need to offer WHP programs that are
      inexpensive, turnkey, and easy to adapt.

PMID- 23113781
TI  - Health concerns of the U.S. fire service: perspectives from the firehouse.
AB  - PURPOSE: Firefighters are expected to respond to any domestic emergency at a
      moment's notice, and therefore their health and readiness are key to the public
      safety net. Although emerging research is focusing on understanding firefighters'
      increased risk for disease and injury, the perspectives of fire service personnel
      is lacking. DESIGN: This study uses the cross-sectional qualitative data
      collection techniques of key informant interviews and focus groups. SETTING: Data
      collection occurred with a national sample of firefighters from 28 (municipal and
      federal) career fire departments. PARTICIPANTS: Participants were 332 career
      firefighters (57.2%), company officers (23.4%), fire chiefs (15.4%), and other
      fire service personnel (3.9%). METHOD: Focus groups and informant interviews were
      conducted with firefighters, fire chiefs, health promotion personnel, and medical
      directors to assess attitudes, opinions, and perceptions about firefighter
      health. RESULTS: Major themes that developed among fire service personnel
      included concerns about cancer, risk of cardiovascular disease, the importance of
      and barriers to physical fitness, the food culture of the firehouse,
      psychological stress resulting from repeated exposure to trauma, sleep
      disruptions, injuries, and risk for infectious disease. Health concerns
      identified by firefighters are juxtaposed with current efforts and trends within
      the national fire service. CONCLUSIONS: The health concerns of firefighters
      parallel both available epidemiological research and the health priorities of
      national fire service organizations. Unfortunately, these concerns often are in
      contrast with efforts by local governments to limit their financial liability for
      illnesses presumed to be caused by occupational exposures and long-held
      traditions in the fire service. This study highlights the need for
      epidemiological surveillance of firefighters and innovative health and
      organizational policy in the fire service. Future directions for the fire
      service, the public health community, and researchers are discussed.

PMID- 23113782
TI  - Impact of financial incentives on behavior change program participation and risk
      reduction in worksite health promotion.
AB  - PURPOSE: To examine the impact of financial incentives on behavior change program
      registration, completion, and risk improvement rates. DESIGN: Retrospective
      cohort study conducted to observe the relationship between financial incentives
      and behavior change program registration, completion, and risk improvement rates.
      SETTING: Large public- or private-sector employers. SUBJECTS: Twenty-four
      organizations (n = 511,060 eligible employees) that offered comprehensive
      worksite health promotion (WHP) programs. INTERVENTION: Financial incentives
      offered for completion of a behavior change program as part of a WHP program.
      MEASURES: Behavior change program registration and completion data were obtained
      from standard reports. Company-level risk change was calculated from the average
      per-person number of risks on baseline and follow-up health risk assessments.
      Incentive design was determined from questionnaires completed by WHP program
      managers. ANALYSIS: Average registration rates, program completion rates, and
      risk improvement rates were compared using t-tests for companies that did versus
      did not offer incentives. Comparisons were also made between companies with
      incentives of less than $100 and those with incentives of $100 or more.
      Correlations between incentive value and outcome variables were assessed using
      Pearson correlations. RESULTS: Companies that offered incentives had
      significantly higher health coaching completion rates than companies not offering
      an incentive (82.9% vs. 76.4%, respectively, p = .017) but there was no
      significant association with registration (p = .384) or risk improvement rates (p
      = .242). Incentive values were not significantly associated with risk improvement
      rates (p = .240). CONCLUSION: Offering incentives for completing behavior change
      programs may increase completion rates, but increased health improvement does not
      necessarily follow.

PMID- 23113783
TI  - Health and health care utilization among obese and diabetic baby boomers and
      older adults.
AB  - PURPOSE: Examine how sociodemographic, health, behavioral, and health care
      utilization factors are associated with being obese or having diabetes among baby
      boomers and older adults. DESIGN: Cross-sectional data were drawn from the 2007
      2008 National Health and Nutrition Examination Survey. SETTING: United States.
      SUBJECTS: A sample of 3439 baby boomers and older adults included (mean age, 62
      years). MEASURES: Covariates included sociodemographics, health outcomes,
      behaviors, and inpatient and outpatient health care utilization. ANALYSIS:
      Multinomial logistic regression was used to explore which similar or different
      covariates were associated with different health states between baby boomers and
      older adults. RESULTS: Approximately 8% of baby boomers and 10% of older adults
      had the twin diagnoses of obesity and diabetes. Having both obesity and diabetes
      was more common among baby boomers and older adults who were African-American
      (odds ratio [OR] = 1.79, p = .029 for baby boomers; OR = 3.45, p < .001 for older
      adults), perceived their general health as fair/poor (OR = 7.67, p < .001; OR =
      4.13, p < .001), and utilized outpatient care more often (OR = 8.28, p < .001; OR
      = 5.35, p = .004). Being obese only was observed less among baby boomers who were
      current smokers (OR = .45, p < .001), whereas it was observed more among older
      adults who were former smokers (OR = 1.25, p = .046). Having diabetes only was
      observed more among baby boomers who had hypertension (OR = 2.44, p = .01),
      whereas it was observed more among older adults who had very high cholesterol (OR
      = 2.31, p = .029). CONCLUSION: Identifying chronic disease risk factors during
      middle age is important for ameliorating further complications in later life.
      Knowing more about the correlates of obesity and diabetes among different age
      groups can help health care planners better target preventive health care
      services.

PMID- 23113786
TI  - Impact of an online healthful eating and physical activity program for college
      students.
AB  - PURPOSE: To identify impact of an online nutrition and physical activity program
      for college students. DESIGN: Randomized, controlled trial using online
      questionnaires and on-site physical and fitness assessments with measurement
      intervals of 0 (baseline), 3 (postintervention), and 15 months (follow-up).
      SETTING: Online intervention delivered to college students; a centralized Web
      site was used for recruitment, data collection, data management, and intervention
      delivery. SUBJECTS: College students (18-24 years old, n = 1689), from eight
      universities (Michigan State University, South Dakota State University, Syracuse
      University, The Pennsylvania State University, Tuskegee University, University of
      Rhode Island, University of Maine, and University of Wisconsin). INTERVENTION: A
      10-lesson curriculum focusing on healthful eating and physical activity,
      stressing nondieting principles such as size acceptance and eating competence
      (software developer: Rainstorm, Inc, Orono, Maine). MEASURES: Measurements
      included anthropometrics, cardiorespiratory fitness, fruit/vegetable (FV) intake,
      eating competence, physical activity, and psychosocial stress. ANALYSIS: Repeated
      measures analysis of variance for outcome variables. RESULTS: Most subjects were
      white, undergraduate females (63%), with 25% either overweight or obese.
      Treatment group completion rate for the curriculum was 84%. Over 15 months, the
      treatment group had significantly higher FV intake (+.5 cups/d) and physical
      activity participation (+270 metabolic equivalent minutes per week) than
      controls. For both groups, anthropometric values and stress increased, and
      fitness levels decreased. Gender differences were present for most variables.
      First-year males and females gained more weight than participants in other school
      years. CONCLUSION: A 10-week online nutrition and physical activity intervention
      to encourage competence in making healthful food and eating decisions had a
      positive, lasting effect on FV intake and maintained baseline levels of physical
      activity in a population that otherwise experiences significant declines in these
      healthful behaviors.

PMID- 23113787
TI  - Kaiser Permanente's Community Health Initiative in Northern California:
      evaluation findings and lessons learned.
AB  - PURPOSE: To describe the evaluation findings and lessons learned from the Kaiser
      Permanente Healthy Eating Active Living-Community Health Initiative. DESIGN:
      Mixed methods design: qualitative case studies combined with pre/post population
      level food and physical activity measures, using matched comparison schools for
      youth surveys. SETTING: Three low-income communities in Northern California
      (combined population 129,260). SUBJECTS: All residents of the three communities.
      INTERVENTION: Five-year grants of $1.5 million awarded to each community to
      support the implementation of community- and organizational-level policy and
      environmental changes. Sectors targeted included schools, health care settings,
      worksites, and neighborhoods. MEASURES: Reach (percentage exposed) and strength
      (effect size) of the interventions combined with population-level measures of
      physical activity (e.g., minutes of physical activity) and nutrition (e.g., fruit
      and vegetable servings). ANALYSIS: Pre/post analysis of population level
      measures, comparing changes in intervention to comparison for youth survey
      measures. RESULTS: The population-level results were inconclusive overall, but
      showed positive and significant findings for four out of nine comparisons where
      "high-dose" (i.e., greater than 20% of the population reached and high strength)
      strategies were implemented, primarily physical activity interventions targeting
      school-age youth. CONCLUSION: The positive and significant changes for the high
      dose strategies suggest that if environmental interventions are of sufficient
      reach and strength they may be able to favorably impact obesity-related
      behaviors.

PMID- 23113789
TI  - Compression of morbidity: a personal, research, and national fiscal solvency
      perspective.
AB  - Soon to be published research shows that people with positive health practices
      reduced the period of disability at the end of life by an estimated six to nine
      years. If improved health habits could reduce the period of disability for the
      entire population of the United States by this amount, spending on Medicare,
      Medicaid, and Social Security would drop substantially, and state and federal
      income tax revenues would increase substantially. This is critically important
      given that the Congressional Budget Office has projected that 100% of federal tax
      revenues will be consumed by Medicare, Medicaid, and Social Security by the year
      2050 if current health and spending trends continue.

PMID- 23113791
TI  - Parallel beta-sheet vibrational couplings revealed by 2D IR spectroscopy of an
      isotopically labeled macrocycle: quantitative benchmark for the interpretation of
      amyloid and protein infrared spectra.
AB  - Infrared spectroscopy is playing an important role in the elucidation of amyloid
      fiber formation, but the coupling models that link spectra to structure are not
      well tested for parallel beta-sheets. Using a synthetic macrocycle that enforces
      a two stranded parallel beta-sheet conformation, we measured the lifetimes and
      frequency for six combinations of doubly (13)C?(18)O labeled amide I modes using
      2D IR spectroscopy. The average vibrational lifetime of the isotope labeled
      residues was 550 fs. The frequencies of the labels ranged from 1585 to 1595 cm(
      1), with the largest frequency shift occurring for in-register amino acids. The
      2D IR spectra of the coupled isotope labels were calculated from molecular
      dynamics simulations of a series of macrocycle structures generated from replica
      exchange dynamics to fully sample the conformational distribution. The models
      used to simulate the spectra include through-space coupling, through-bond
      coupling, and local frequency shifts caused by environment electrostatics and
      hydrogen bonding. The calculated spectra predict the line widths and frequencies
      nearly quantitatively. Historically, the characteristic features of beta-sheet
      infrared spectra have been attributed to through-space couplings such as
      transition dipole coupling. We find that frequency shifts of the local carbonyl
      groups due to nearest neighbor couplings and environmental factors are more
      important, while the through-space couplings dictate the spectral intensities. As
      a result, the characteristic absorption spectra empirically used for decades to
      assign parallel beta-sheet secondary structure arises because of a redistribution
      of oscillator strength, but the through-space couplings do not themselves
      dramatically alter the frequency distribution of eigenstates much more than
      already exists in random coil structures. Moreover, solvent exposed residues have
      amide I bands with >20 cm(-1) line width. Narrower line widths indicate that the
      amide I backbone is solvent protected inside the macrocycle. This work provides
      calculated and experimentally verified couplings for parallel beta-sheets that
      can be used in structure-based models to simulate and interpret the infrared
      spectra of beta-sheet containing proteins and protein assemblies, such as amyloid
      fibers.

PMID- 23113792
TI  - Mutational analysis of the FST gene in Chinese women with idiopathic premature
      ovarian failure.
AB  - OBJECTIVE: Recent animal studies have suggested that loss of follistatin (FST)
      may result in premature cessation of ovarian function. Our objective was to
      investigate whether mutations in the FST coding region are present in Chinese
      women with idiopathic premature ovarian failure (POF). METHOD: The matched case
      control study took place in the First Affiliated Hospital of Nanjing Medical
      University with 80 idiopathic POF patients and 80 matched controls. There were no
      interventions. The entire FST coding region was analyzed by direct sequencing in
      all subjects. RESULTS: Three FST gene variants were identified, namely c.270C> G,
      c.598G> C and c.953-184A> T (rs722910). The synonymous variant (c.270C> G) in
      exon 2 was present in the heterozygous state in a single POF patient. The novel
      c.598G> C missense mutation, located in exon 4 and resulting in an alanine to
      proline substitution at amino acid 200, was detected in a single healthy control.
      There was no difference in genotype distribution and allele frequency of the
      known single nucleotide polymorphism rs722910 between POF patients and controls.
      CONCLUSION: Although we did not find any evidence that it is a disease-causing
      gene, our study is the first to evaluate the role of the FST gene in Chinese
      women with idiopathic POF.

PMID- 23113793
TI  - Subacute endocarditis caused by Yersinia enterocolitica: a case report.
AB  - Yersinia enterocolitica is an unusual cause of septicaemia, usually occurring in
      immunocompromised hosts. Endocardial involvement is rare and generally presents
      as acute endocarditis. We describe the case of a 73-y-old woman, apparently
      without risk factors for endocarditis, admitted to hospital for persistent fever
      of unknown origin, arthralgia, and weight loss. Y. enterocolitica was isolated
      from blood and urine cultures, and echocardiography showed a pedunculated
      vegetation attached to the non-coronary cusp of the aortic valve. Symptoms and
      fever resolved after 3 days of intravenous cefotaxime plus amikacin, which were
      continued for the 2 weeks of her hospital stay; this treatment was followed by
      intravenous ceftriaxone after discharge. We hypothesized that a chemotherapy
      course administered 2 months previously for breast cancer might have been a
      predisposing factor for the Y. enterocolitica valvular infection and that immune
      system recovery contributed to mitigate the clinical presentation as subacute
      endocarditis.

PMID- 23113794
TI  - Aryllithiums with increasing steric crowding and lipophilicity prepared from
      chlorides in diethyl ether. The first directly prepared room-temperature-stable
      dilithioarenes.
AB  - A convenient procedure has been developed for the preparation of synthetically
      useful, room-temperature-stable aryllithiums starting from aryl chlorides and
      lithium metal. The method provides a route to aryllithiums which have previously
      not been accessible cleanly or could only be prepared by using more expensive
      starting materials.

PMID- 23113795
TI  - Cyberterrorism: is the U.S. healthcare system safe?
AB  - The Internet has brought with it many benefits; key among them has been its
      ability to allow the expansion of communication and transfer of all kinds of
      information throughout the U.S. healthcare system. As a consequence, healthcare
      has become increasingly dependent on the activities carried out in that
      environment. It is this very dependence that increases the likelihood of
      individuals or organizations conducting activities through the Internet that will
      cause physical and/or psychological harm. These activities have become known by
      the term "cyberterrorism." In the healthcare landscape this can appear in a
      variety of forms, such as bringing down a hospital computer system or publicly
      revealing private medical records. Whatever shape it takes, the general effects
      are the same: patient care is compromised, and trust in the health system is
      diminished. Fortunately no significant cyber attack has been successfully
      launched against a U.S. healthcare organization to date. However, there is
      evidence to suggest that cyber threats are increasing and that much of the U.S.
      healthcare system is ill equipped to deal with them. Securing cyberspace is not
      an easy proposition as the threats are constantly changing, and recognizing that
      cyberterrorism should be part of a broader information technology risk management
      strategy, there are several"best practices" that can be adopted by healthcare
      organizations to protect themselves against cyber attacks.

PMID- 23113796
TI  - Text-to-audiovisual speech synthesizer for children with learning disabilities.
AB  - Learning disabilities affect the ability of children to learn, despite their
      having normal intelligence. Assistive tools can highly increase functional
      capabilities of children with learning disorders such as writing, reading, or
      listening. In this article, we describe a text-to-audiovisual synthesizer that
      can serve as an assistive tool for such children. The system automatically
      converts an input text to audiovisual speech, providing synchronization of the
      head, eye, and lip movements of the three-dimensional face model with appropriate
      facial expressions and word flow of the text. The proposed system can enhance
      speech perception and help children having learning deficits to improve their
      chances of success.

PMID- 23113797
TI  - Unique gene alterations are induced in FACS-purified Fos-positive neurons
      activated during cue-induced relapse to heroin seeking.
AB  - Cue-induced heroin seeking after prolonged withdrawal is associated with neuronal
      activation and altered gene expression in prefrontal cortex (PFC). However, these
      previous studies assessed gene expression in all neurons regardless of their
      activity state during heroin seeking. Using Fos as a marker of neural activity,
      we describe distinct molecular alterations induced in activated versus non
      activated neurons during cue-induced heroin seeking after prolonged withdrawal.
      We trained rats to self-administer heroin for 10 days (6 h/day) and assessed cue
      induced heroin seeking in extinction tests after 14 or 30 days. We used
      fluorescent-activated cell sorting (FACS) to purify Fos-positive and Fos-negative
      neurons from PFC 90 min after extinction testing. Flow cytometry showed that Fos
      immunoreactivity was increased in less than 10% of sparsely distributed PFC
      neurons. mRNA levels of the immediate early genes fosB, arc, egr1, and egr2, as
      well as npy and map2k6, were increased in Fos-positive, but not Fos-negative,
      neurons. In support of these findings, double-label immunohistochemistry
      indicated substantial coexpression of neuropeptide Y (NPY)- and Arc
      immunoreactivity in Fos-positive neurons. Our data indicate that cue-induced
      relapse to heroin seeking after prolonged withdrawal induces unique molecular
      alterations within activated PFC neurons that are distinct from those observed in
      the surrounding majority of non-activated neurons.

PMID- 23113798
TI  - Personal continuity of care in Norwegian general practice: a national cross
      sectional study.
AB  - OBJECTIVE: Personal continuity is regarded as a core value in general practice.
      The aim of this study was to determine the level of personal continuity in
      Norwegian general practice. An investigation was made of the associations between
      high levels of personal continuity and patient, general practitioner (GP), and
      list characteristics. DESIGN: Cross-sectional register-based study. SETTING:
      Norwegian general practice in 2009. SUBJECTS: 3220 GPs and 3 725 998 patients on
      the GP lists. MAIN OUTCOME MEASURES: The Usual Provider Continuity Index (UPC),
      which measures the proportion of consultations made by the usual GP, was
      estimated for patients and aggregated to the GP list level. GPs were grouped into
      quartiles based on the UPC. Being a GP with a UPC in the two highest quartiles
      (UPC >= 0.80) was the outcome in the statistical analyses. STATISTICS: Poisson
      regression models were used to estimate relative risks (RR). RESULTS: The overall
      UPC was 0.78, increasing gradually from 0.68 in patients < 15 years of age to
      0.86 for patients >= 60 years of age, and from 0.75 to 0.83 for patients with < 3
      annual consultations compared with patients with > 10 consultations. A UPC > 0.80
      was associated with longer patient lists and high GP consultation rates. Working
      in municipalities with < 10 000 residents was negatively associated with a high
      UPC. The UPC level for GPs was associated with total utilization of GP
      consultations in the list populations. CONCLUSION: Overall, the Norwegian goal of
      a personal GP has been achieved; however, there are substantial variations
      between GPs and lower UPCs among young patients and in smaller municipalities.

PMID- 23113799
TI  - Preparation of (131)I-Pyrimethamine and evaluation for scintigraphy of
      experimentally Toxoplasma gondii-infected rats.
AB  - We aimed to assess the ability of (131)I-Pyrimethamine scintigraphy to detect the
      lesions of Toxoplasma gondii infection. An experimental model of toxoplasmosis
      was developed. The presence of toxoplasmosis was confirmed 60 days after
      implantation. Pyrimethamine was radioiodinated with I-131. The radioligand was
      validated by the requisite quality control tests to check its radiolabeling
      efficiency, in vitro stability and radiochemical purity etc. (131)I-Pyrimethamine
      (specific activity: 7.08 MBq/umol) was injected intravenously into the tail vein
      of the control and infected rats. Static whole body images of the rats were
      acquired under the gamma camera at 5 min, 45 min, 2 h, 6 h, and 24 h following
      the intravenous administration of the radioactivity (3.7 MBq/rat). Then the
      scintigraphic data were analyzed both visually and semiquantitatively. Regions of
      interest (ROIs) were drawn over the organs (thyroid, stomach, liver, bladder, and
      soft tissues) to calculate the ratios of the radiotracer in infected vs. control
      rats. The mean ratio of radiotracer in infected/control rats in the liver and
      diaphragm was over 1 at 45 min which persisted till 24 h. In conclusion, (131)I
      Pyrimethamine may be useful agent for diagnosis toxoplasmosis especially
      involving liver and diaphragm, needs further preclinical validation before being
      extended for use in clinical applications.

PMID- 23113800
TI  - Gray matter volume alterations related to trait dissociation in PTSD and
      traumatized controls.
AB  - OBJECTIVE: This study used voxel-based morphometry (VBM) to investigate brain
      structural alterations related to trait dissociation and its relationship with
      post-traumatic stress disorder (PTSD). METHOD: Thirty-two subjects either
      developing (N = 15) or non-developing (N = 17) PTSD underwent MRI scanning and
      were assessed with the Dissociative Experience Scale (DES), subscales for
      pathological (DES-T) and non-pathological trait (DES-A) dissociation, and other
      clinical measures. Gray matter volume (GMV) was analyzed using VBM as implemented
      in SPM. PTSD and non-PTSD subjects were compared to assess brain alterations
      related to PTSD pathology, whereas correlation analyses between dissociation
      measures and GMV were performed on the whole sample (N = 32), irrespective of
      PTSD diagnosis, to identify alterations related to trait dissociation. RESULTS:
      As compared to traumatized controls, PTSD subjects showed reduced GMV in the
      prefrontal cortex, hippocampus and lingual gyrus. Correlations with dissociation
      measures (DES, DES-T, and DES-A) consistently showed increased GMV in the medial
      and lateral prefrontal, orbitofrontal, parahippocampal, temporal polar, and
      inferior parietal cortices. CONCLUSION: PTSD and dissociation seem to be
      associated with opposite volumetric patterns in the prefrontal cortex. Trait
      dissociation appears to involve increased GMV in prefrontal, paralimbic, and
      parietal cortices, with negligible differences between pathological and non
      pathological dissociation.

PMID- 23113802
TI  - Single-molecule adhesion of a stimuli-responsive oligo(ethylene glycol) copolymer
      to gold.
AB  - Adhesion of environmentally responsive polymers to biocompatible surfaces is an
      important issue that has been explored in several nanobiotechnology applications.
      Here, we prepared multi-responsive statistical copolymers of two oligo(ethylene
      glycol) methyl ether methacrylate macromonomers with differing ethylene glycol
      side chain lengths using RAFT polymerization. The lower critical solution
      temperature of the copolymers was characterized using visible light extinction,
      and the chemical composition and molecular weight were measured using NMR
      spectroscopy and size-exclusion chromatography, respectively. The
      characterization results demonstrated that the transition temperature could be
      controlled by varying the macromonomer feed ratios, and the molecular weight
      could be controlled by varying the amount of the RAFT chain transfer agent in the
      polymerization feed. Using AFM single-molecule force spectroscopy, we measured
      the adhesion characteristics of single copolymer molecules to a gold surface. We
      found that dehydration and collapse of the copolymer in a high ionic strength
      buffer resulted in dramatically reduced bridging length distributions that
      maintained their single-molecule bimodal character. In the collapsed state, the
      polymer exhibited a lower absolute desorption force while cooperativity effects
      were found to increase the desorption force per chain for multi-chain
      interactions. Our results confirmed that the polymer in a collapsed conformation
      exhibited a dramatically reduced volume occupancy above the gold surface. These
      results demonstrate at the single-molecule level how solvent-induced collapse of
      an environmentally responsive copolymer modulates surface adhesion forces and
      bridging length distributions in a controllable way.

PMID- 23113801
TI  - Prevalence, incidence, and residual risks for transfusion-transmitted human
      immunodeficiency virus Types 1 and 2 infection among Chinese blood donors.
AB  - BACKGROUND: There are little data on human immunodeficiency virus (HIV)
      prevalence, incidence, or residual risks for transfusion-transmitted HIV
      infection among Chinese blood donors. STUDY DESIGN AND METHODS: Donations from
      five Chinese blood centers in 2008 to 2010 were screened using two rounds of
      enzyme-linked immunosorbent assay for anti-HIV-1/2. A reactive result in either
      or both rounds led to Western blot confirmatory testing. HIV prevalence among
      first-time donors and incidence among repeat donors were examined. Weighted
      multivariable logistic regression analysis examined correlates of HIV
      confirmatory status among first-time donors. Residual risks were evaluated based
      on incidence among repeat donors. RESULTS: Among 821,320 donations, 40% came from
      repeat donors. A total of 1837 (0.34%) first-time and 577 (0.17%) repeat
      donations screened reactive, among which 1310 and 419 were tested by Western
      blot. A total of 233 (17.7%) first-time and 44 (10.5%) repeat donations were
      confirmed positive. Prevalence was 66 infections per 100,000 (95% confidence
      interval [CI], 59-74) first-time donors. Incidence was 9 of 100,000 (95% CI, 7
      12) person-years among repeat donors. Multivariable logistic regression analysis
      indicates that first-time donors 26 to 45 years old were 1.6 to 1.8 times likely
      to be HIV positive than those 25 years and younger. Donors with some college or
      above education were less likely to be HIV positive than those with middle school
      education, odds ratios (ORs) ranging from 0.35 to 0.60. Minorities were 1.5 times
      likely to be HIV positive than Han majority donors (OR, 1.6; 95% CI, 1.2-2.1).
      HIV residual risk was 5.4 (95% CI, 1.2-12.5) infections per million whole blood
      donations. CONCLUSION: Despite the declining HIV epidemic in China, estimated
      residual risks for transfusion-transmitted HIV infection are still high.

PMID- 23113803
TI  - Engineering light: advances in wavelength conversion materials for energy and
      environmental technologies.
AB  - Upconversion photoluminescence (UC) occurs in optical materials that are capable
      of absorbing low energy photons and emitting photons of higher energy and shorter
      wavelength, while downconversion (DC) materials may absorb one high energy photon
      and emit two of lower energy for quantum yields exceeding unity. These wavelength
      conversion processes allow us to transform electromagnetic radiation so it may be
      more effectively utilized by light-capturing devices and materials. Progress in
      designing more efficient organic and inorganic photochemical conversion systems
      has initiated a recent surge in attempts to apply these processes for practical
      uses, including enhancement of many energy and environmental technologies. In
      this review, we introduce important concepts in UC and DC materials and discuss
      the current status and challenges toward the application of wavelength conversion
      to solar cells, photocatalysis, and antimicrobial surfaces.

PMID- 23113804
TI  - Ruthenium(0) nanoparticles supported on multiwalled carbon nanotube as highly
      active catalyst for hydrogen generation from ammonia-borane.
AB  - Ruthenium(0) nanoparticles supported on multiwalled carbon nanotubes
      (Ru(0)@MWCNT) were in situ formed during the hydrolysis of ammonia-borane (AB)
      and could be isolated from the reaction solution by filtration and characterized
      by ICP-OES, XRD, TEM, SEM, EDX, and XPS techniques. The results reveal that
      ruthenium(0) nanoparticles of size in the range 1.4-3.0 nm are well-dispersed on
      multiwalled carbon nanotubes. They were found to be highly active catalyst in
      hydrogen generation from the hydrolysis of AB with a turnover frequency value of
      329 min-1. The reusability experiments show that Ru(0)@MWCNTs are isolable and
      redispersible in aqueous solution; when redispersed they are still active
      catalyst in the hydrolysis of AB exhibiting a release of 3.0 equivalents of H2
      per mole of NH3BH3 and preserving 41% of the initial catalytic activity even
      after the fourth run of hydrolysis. The lifetime of Ru(0)@MWCNTs was measured as
      26400 turnovers over 29 h in the hydrolysis of AB at 25.0 +/- 0.1  degrees C
      before deactivation. The work reported here also includes the kinetic studies
      depending on the temperature to determine the activation energy of the reaction
      (E(a) = 33 +/- 2 kJ/mol) and the effect of catalyst concentration on the rate of
      the catalytic hydrolysis of AB, respectively.

PMID- 23113805
TI  - Prevalence of biofilm formation in clinical isolates of Candida species causing
      bloodstream infection.
AB  - Candida species are the fourth most common cause of nosocomial invasive
      infections. Biofilm formation is recognised as one virulence factor of Candida
      species. A total of 243 Candida albicans, 81 C. glabrata, 33 C. parapsilosis, 14
      C. dubliniensis, 8 C. tropicalis, 8 C. lusitaniae, 5 C. krusei and 1 C.
      pelliculosa isolates causing bloodstream infections were evaluated for biofilm
      formation. The biofilm formed on silicone elastomer preincubated with human serum
      was quantified by estimation of the metabolic activity through XTT assay and
      visualised by light and scanning electron microscopy. Forty per cent of the C.
      albicans isolates formed biofilm compared to 88.7% of the non-albicans Candida
      isolates (P < 0.0001). Among non-albicans Candida spp., biofilm formation was
      most commonly observed in C. tropicalis and C. lusitaniae (100%), followed by C.
      glabrata (95%), C. dubliniensis (85.7%) and C. parapsilosis (66.7%). A
      quantitative correlation was observed between the amount of biofilm observed
      microscopically, and that determined by metabolic activity measurements. The
      biofilms of all Candida species were composed of basal yeast cells with the
      exception of C. parapsilosis which produced biofilms consisting of pseudohyphae
      and aggregated yeast cells. These results suggest that biofilm formation as a
      virulence factor might have a higher significance for non-albicans Candida
      species than for C. albicans.

PMID- 23113806
TI  - Polysaccharide from seeds of Plantago asiatica L. increases short-chain fatty
      acid production and fecal moisture along with lowering pH in mouse colon.
AB  - Mice (20.0 +/- 2.0 g, n = 48 per group) were given 30 days oral administration of
      polysaccharide from Plantago asiatica L. seeds at the dose of 0.4 g/kg body
      weight by gavage to investigate the effects of the polysaccharide on mouse colon.
      Results showed that the concentrations of total short-chain fatty acids (SCFA),
      acetic, propionic, and n-butyric acids in mouse colonic content of polysaccharide
      treated group were all significantly higher than that of control group (water) (p
      < 0.05). In addition, moisture of mouse colonic content of polysaccharide treated
      group was also notably higher than that of the control group (p < 0.05)
      indicating the intake of polysaccharide from P. asiatica L. resulted in a
      stronger water-holding capacity for colonic content throughout the experimental
      period. Furthermore, a decreased pH (from 7.5 +/- 0.1 to 7.2 +/- 0.1) was
      observed in mouse colon of the polysaccharide treated group compared with the
      control group (pH from 7.5 +/- 0.1 to 7.5 +/- 0.1). These results suggested that
      the intake of the polysaccharide from P. asiatica L. might be beneficial for the
      colon health.

PMID- 23113807
TI  - Erectile dysfunction and depression in patients with chronic lead poisoning.
AB  - In this retrospective study, we aimed to evaluate the relationship between
      erectile dysfunction (ED) and chronic lead intoxication (CLI) as well as the role
      of depression in this relationship. We compared the findings of 26 male patients
      with CLI and 24 male patients as the control group between November 2008 and
      January 2009. The blood lead levels and smoking index of patients were evaluated
      for both groups. The International Index of Erectile Dysfunction-erectile
      function domain (EFD) and Beck Depression Inventory (BDI) were obtained and
      reviewed in both groups. The mean blood lead levels of patients in the CLI and
      control groups were 42.1 and 3.2 MUg dl(-1) respectively (P < 0.01). The mean
      interval of lead exposure of patients in CLI group was 71.5 (6-360) months. EFD
      scores of patients in CLI group were significantly lower, and number of patients
      with ED in CLI group was statistically higher (P < 0.05). BDI scores of patients
      in CLI group were significantly higher (P < 0.05). We detected a mildly negative
      and statistically significant relationship between the EFD scores and blood lead
      levels (r = -0.453 and P < 0.05). Our results showed that the increased frequency
      of ED is an independent factor in CLI group. 

PMID- 23113808
TI  - HILIC- and SCX-based quantitative proteomics of Chlamydomonas reinhardtii during
      nitrogen starvation induced lipid and carbohydrate accumulation.
AB  - Nitrogen starvation induced changes in carbohydrate and lipid content is
      described in several algal species. Although these phenotypic changes are
      desirable, such manipulations also significantly deteriorate culture health,
      ultimately halting growth. To optimize biofuel production from algae, it is
      desirable to induce lipid accumulation without compromising cell growth and
      survival. In this study, we utilized an 8-plex iTRAQ-based proteomic approach to
      assess the model alga Chlamydomonas reinhardtii CCAP 11/32CW15+ under nitrogen
      starvation. First-dimension fractionation was conducted using HILIC and SCX. A
      total of 587 proteins were identified (>=3 peptides) of which 71 and 311 were
      differentially expressed at significant levels (p<0.05), during nitrogen stress
      induced carbohydrate and lipid production, respectively. Forty-seven percent more
      changes with significance were observed with HILIC compared to SCX. Several
      trends were observed including increase in energy metabolism, decrease in
      translation machinery, increase in cell wall production and a change of balance
      between photosystems I and II. These findings point to a severely compromised
      system where lipid is accumulated at the expense of normal functioning of the
      organism, suggesting that a more informed and controlled method of lipid
      induction than gross nutrient manipulation would be needed for development of
      sustainable processes.

PMID- 23113809
TI  - Development of normative neuropsychological performance in Thailand for the
      assessment of HIV-associated neurocognitive disorders.
AB  - International studies of HIV-associated neurocognitive disorder (HAND) are needed
      to determine the viral and host factors associated with cognitive impairment
      particularly as more than 80% of HIV+ subjects reside in resource-limited
      settings. Recent diagnostic nomenclature of HAND requires comparison of cognitive
      performance specifically to local normative data. To evaluate this need for local
      norms, we compared normative data obtained locally in Thailand to Western norms.
      The current study examined cognitive performance in 477 seronegative Thai
      participants (male = 211, female = 266) who completed a battery of tests
      sensitive to cognitive changes in HIV. The cohort was divided into three age
      brackets (20-34; 35-49; 50-65 years) and four educational levels (no education or
      primary education, less than secondary certificate, high-school/associates
      degree, bachelor's degree or greater). The Thai cohort was compared (using
      analysis of covariance, ANCOVA) on a number of measures to a seronegative US
      cohort (n = 236; male = 198, female = 38) to examine cultural differences in
      performance. Normative data are provided with age and education stratification.
      The Thai and US groups performed significantly differently on all
      neuropsychological measures with the exception of verbal fluency. The Thai group
      performed better on measures of verbal learning (p < .001) and memory (p < .001)
      and measures of psychomotor speed (p < .001). Education was a more powerful
      predictor of performance in the Thai cohort than in the US group. These results
      highlight the continued need for the development of normative data within local
      populations. The use of Western norms as a comparison group could lead to
      inaccurate identification of HAND in culturally distinct groups.

PMID- 23113810
TI  - Radical amination of C(sp3)-H bonds using N-hydroxyphthalimide and dialkyl
      azodicarboxylate.
AB  - A direct conversion of C(sp(3))-H bonds to C(sp(3))-N bonds has been achieved by
      utilizing catalytic N-hydroxyphthalimide (NHPI) and stoichiometric dialkyl
      azodicarboxylate. NHPI functions as a precursor of the electron-deficient
      phthalimide N-oxyl radical (PINO) to abstract hydrogens, and dialkyl
      azodicarboxylate acts as a trapping agent of the resultant carbon radical to
      generate the hydrazine derivatives. This C-H amination proceeds in a highly
      chemoselective manner with a wide applicability to functionalize benzylic,
      propargylic, and aliphatic C-H bonds. Furthermore, the obtained hydrazine
      compounds were readily converted to the corresponding carbamates or amines.
      Hence, the present protocol for direct introduction of the nitrogen functionality
      serves as a powerful tool for efficient construction of nitrogen-substituted
      natural products and pharmaceuticals.

PMID- 23113811
TI  - Mycophenolate mofetil versus azathioprine as maintenance therapy for lupus
      nephritis: a meta-analysis.
AB  - AIM: The options for long-term maintenance therapy in lupus nephritis (LN) remain
      controversial. This meta-analysis of randomized controlled trials (RCTs) assessed
      the prognosis and safety of mycophenolate mofetil (MMF) versus azathioprine (AZA)
      used as maintenance therapy for lupus nephritis. METHODS: The data of Cochrane
      Library, PubMed, EMBASE were retrieved to search the studies about the RCT
      studies that compared MMF with AZA used as maintenance therapy for lupus
      nephritis. We extracted the data reflecting prognosis, which included mortality,
      end-stage renal failure (ESRF), renal relapse, doubling serum creatinine, and
      adverse effects, then further analyzed the combined results of data and
      calculated the relative risk (RR). RESULTS: Four RCT studies including 328
      patients were enrolled into our meta-analysis. There was no difference between
      the patients receiving either MMF or AZA for maintenance therapy in preventing
      relapse, progression to end-stage renal failure, death and doubling of serum
      creatinine. MMF is not superior to AZA in terms of the risks of infection and
      gastrointestinal upset, but fewer patients receiving MMF developed leukopenia (RR
      0.12; 95% confidence interval (CI), 0.04-0.39; P = 0.0004) and amenorrhoea (RR
      0.17; 95% CI, 0.04-0.72; P = 0.02) than those receiving AZA. CONCLUSION: The
      current limited evidence suggests that MMF offers similar prognosis as AZA for
      maintenance therapy, while MMF appears safer than AZA in the treatment of lupus
      nephritis.

PMID- 23113812
TI  - Acute-phase proteins, oxidative stress and enzyme activities of blood serum and
      peritoneal fluid in cattle with abomasal displacement.
AB  - BACKGROUND: Blood serum and peritoneal fluid acute-phase proteins, oxidative
      stress indicators, and some enzymes could be used for evaluation of abomasal
      tissue damage because of displacement in displaced abomasum (DA) cases.
      OBJECTIVES: The aim of this study was to investigate the concentrations of acute
      phase proteins, oxidative stress indicators, and activities of enzymes in blood
      serum and peritoneal fluid in cattle with right displaced abomasum (RDA) and left
      displaced abomasum (LDA) and in healthy cows. ANIMALS: A total of 60 Holstein
      Friesian cows in early lactation were used, 31 with left and 9 with right
      displaced abomasum without volvulus diagnosis and no other postpartum disease,
      and 20 healthy cows as a control. MATERIALS AND METHODS: DA diagnosis in dairy
      cows consisted of physical examination, laboratory, and specific DA tests. Acute
      phase proteins, oxidative stress indicators, and enzyme activities were measured
      in blood serum and peritoneal fluid. RESULTS: In the RDA group, serum haptoglobin
      (HPG), serum amyloid A (SAA), malondialdehyde (MDA), adenosine deaminase (ADA),
      myeleperoxidase (MPO), aspartate aminotransferase (AST), creatine kinase (CK,
      creatine kinase-MB (CK-MB), and gamma-glutamyl transferase (GGT) activity
      increased significantly, and serum HPG, MDA, ADA, and AST concentrations
      increased significantly in the LDA group (P < .05). Peritoneal fluid HPG, MDA,
      ADA, MPO, ALP, GGT, and LDH concentrations increased significantly, whereas NO
      concentrations reduced significantly in the RDA group, and HPG, MDA, ADA, and TP
      concentrations increased significantly, whereas concentrations of NO reduced
      significantly in the LDA group (P < .05). CONCLUSIONS AND CLINICAL IMPORTANCE:
      There are acute-phase responses, oxidative stress, and abomasal tissue damage
      because of displacement in DA cases. Especially, HPG, MDA, ADA, and MPO
      concentrations can provide specific information to help in understanding these
      changes.

PMID- 23113813
TI  - The validity of the Health-Relevant Personality Inventory (HP5i) and the Junior
      Temperament and Character Inventory (JTCI) among adolescents referred for a
      substance misuse problem.
AB  - The aim was to study the validity of 2 personality instruments, the Health
      Relevant Personality Inventory (HP5i) and the Junior Temperament and Character
      Inventory (JTCI), among adolescents with a substance use problem. Clinical
      interviews were completed with 180 adolescents and followed up after 12 months.
      Discriminant validity was demonstrated in the lack of correlation to intelligence
      in both instruments' scales. Two findings were in support of convergent validity:
      Negative affectivity (HP5i) and harm avoidance (JTCI) were correlated to
      internalizing symptoms, and impulsivity (HP5i) and novelty seeking (JTCI) were
      correlated to externalizing symptoms. The predictive validity of JTCI was partly
      supported. When psychiatric symptoms at baseline were controlled for,
      cooperativeness predicted conduct disorder after 12 months. Summarizing, both
      instruments can be used in adolescent clinical samples to tailor treatment
      efforts, although some scales need further investigation. It is important to
      include personality assessment when evaluating psychiatric problems in
      adolescents.

PMID- 23113814
TI  - Ekbom's syndrome or real ectoparasitosis? An unexpected outcome of hidden
      springtails.

PMID- 23113815
TI  - Lipopeptide biosurfactants from Paenibacillus polymyxa inhibit single and mixed
      species biofilms.
AB  - Although biofilms are recognised as important in microbial colonisation,
      solutions to their inhibition are predominantly based on planktonic assays. These
      solutions have limited efficacy against biofilms. Here, a series of biofilm
      orientated tests were used to identify anti-biofilm compounds from marine micro
      flora. This led to the isolation of a complex of anti-biofilm compounds from an
      extract of Paenibacillus polymyxa (PPE). A combination of rpHPLC and mass
      spectrometry identified the principle components of PPE as fusaricidin B (LI
      FO4b) and polymyxin D1, with minor contributions from surfactins. This complex
      (PPE) reduced the biofilm biomass of Bacillus subtilis, Micrococcus luteus,
      Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus bovis. In
      contrast, ampicillin was only effective against S. aureus. PPE also inhibited a
      self-assembling marine biofilm (SAMB) in co-incubation assays by 99.3% +/- 1.9
      and disrupted established SAMB by 72.4% +/- 4.4, while ampicillin showed no
      significant reduction. The effectiveness of this complex of lipopeptides against
      single and multispecies biofilms suggests a future role in biofilm prevention
      strategies.

PMID- 23113817
TI  - Bacteremia in Swedish hematological patients with febrile neutropenia: bacterial
      spectrum and antimicrobial resistance patterns.
AB  - BACKGROUND: The etiology of bacteremia in hematological patients with febrile
      neutropenia differs geographically and changes over time. Since efficient
      empirical antibiotic treatment depends on relevant knowledge of the bacterial
      panorama, the aim of this study was to describe the prevalence of bacteremia, the
      bacterial spectrum, and the resistance patterns of the isolates in this group
      today. METHODS: In a cross-sectional study, routine blood cultures from febrile
      episodes occurring in adult patients with hematological disorders and neutropenia
      presenting to Karolinska University Hospital, Stockholm, Sweden during a 24-month
      period, were analyzed. RESULTS: A total of 142 febrile neutropenic episodes
      occurring in 124 hematological patients were included in the study. Bacteremia
      was documented in 27% of the episodes, and of these, 58% were due to Gram
      positive pathogens. The most common isolates were viridans streptococci,
      coagulase-negative staphylococci, and Escherichia coli. Low levels of antibiotic
      resistance were detected. The underlying diagnosis of non-Hodgkin's lymphoma
      (NHL) was independently negatively associated with documented bacteremia (p <
      0.01). CONCLUSIONS: The prevalence of bacteremia and the bacterial spectrum were
      consistent with recent Scandinavian reports. Substantially lower levels of
      antimicrobial resistance were registered compared to those found in other
      European centers. Patients with NHL were less likely to have documented
      bacteremia in this study.

PMID- 23113818
TI  - Role of proton-coupled electron transfer in the redox interconversion between
      benzoquinone and hydroquinone.
AB  - Benzoquinone/hydroquinone redox interconversion by the reversible
      Os(dmb)(3)(3+/2+) couple over an extended pH range with added acids and bases has
      revealed the existence of seven discrete pathways. Application of
      spectrophotometric monitoring with stopped-flow mixing has been used to explore
      the role of PCET. The results have revealed a role for phosphoric acid and
      acetate as proton donor and acceptor in the concerted electron-proton transfer
      reduction of benzoquinone and oxidation of hydroquinone, respectively.

PMID- 23113819
TI  - Exploring the self-assembly of polar dimeric capsules using molecular rulers.
AB  - A homologous series of N,N,N',N'-tetramethylalkyl-N,N'-dioxides is used to probe
      the level of guest induced fit attainable in the assembly of a dimeric capsule
      based on tetraurea benzyl calix[4]pyrrole components. A sensible enhancement of
      the capsule's volume was observed in response to guest size for n = 2, 3, and 4.
      In turn, larger guests adopted folded conformations to adapt to the capsule's
      dimensions.

PMID- 23113820
TI  - Predictive value of stabilometry and fear of falling on falls in postmenopausal
      women.
AB  - OBJECTIVES: Falls are one of the leading causes of fractures and impaired quality
      of life in the elderly, and they are related to balance deficit and to fear of
      falls. The purpose of our study is to evaluate predictors of falls in the 50-65
      year-old postmenopausal population. METHODS: A prospective cohort study was
      conducted on 96 postmenopausal women. Fear of falling and postural stability were
      assessed by using the FES-I (Falls Efficacy Scale-International) and a force
      platform, respectively. Fall frequency was determined in the 12-month follow-up
      study period. Multivariate logistic regression was used to identify predictive
      factors of falls. RESULTS: Fear of falls, the FES-I scale and four stabilometric
      parameters, specifically under eyes-closed condition, were significantly higher
      in the group of fallers. The root mean square amplitude in the medial-lateral
      direction with eyes closed (RMSXec) (odds ratio 5.1, 95% confidence interval (CI)
      1.6-15.5, p = 0.004) and FES-I (odds ratio 3.4, 95% CI 1.1-10.5, p = 0.026) were
      the best independent predictive factors of the risk of falling. CONCLUSIONS:
      RMSXec > 0.133 was the best predictive factor for falls in our group of 50-65
      year-old postmenopausal women studied, and a FES-I score > 20 could predict falls
      in this population.

PMID- 23113821
TI  - The scales of psychological capacities: adaptation to an adolescent population.
AB  - Given the dearth of pediatric outcome measures, Wallerstein's "scales of
      psychological capacities" (SPC), measuring psychotherapy changes with adults and
      reflecting shifts in character without specific adherence to a school of
      personality, was adapted to adolescents (Ad-SPC) and examined psychometrically.
      Twelve child psychoanalysts were consulted for content validity. Two
      investigators determined it to have high face validity after administering it to
      40 adolescents. High inter-rater reliability was achieved for individual scale
      items. Construct validity was determined using Pearson correlations between
      multiple Ad-SPC items and co-administered validated measures of psychopathology.
      Preliminary psychometric properties support the Ad-SPC's potential for
      applicability in adolescent psychotherapy.

PMID- 23113822
TI  - The global debate over HIV-related travel restrictions: framing and policy
      change.
AB  - In 2010, the US repealed Section 212(a) of the Immigration and Nationality Act,
      which stated that a non-citizen determined to have a 'communicable disease of
      public health significance', is not admissible into the country without a waiver.
      This included HIV+ non-citizens. In the same year, several other countries,
      including China and South Korea, removed similar restrictions. This paper
      examines the global debate over HIV-related travel restrictions that has been
      ongoing since the mid-1980s and attempts to account for these recent policy
      changes. Entry restrictions have almost always been justified as necessary in two
      ways: to protect public health from the supposed threat posed by the entry of
      people living with HIV, and to limit the costs HIV+ migrants impose on domestic
      health systems. Opponents of these restrictions have consistently sought to
      challenge the evidence underpinning these claims and also to re-frame the issue
      in rights terms. However, in this paper I argue that this re-framing was not in
      itself sufficient to bring about policy change. Contributing to the literature on
      norm building and transnational advocacy both within and beyond global health,
      this article argues that some other crucial factors also have to be taken into
      account, including the changing political context (both domestic and
      international) and the network building strategies employed by opponents of the
      restrictions from 2008 onwards.

PMID- 23113823
TI  - Modeling the transmission risk of emerging infectious diseases through blood
      transfusion.
AB  - BACKGROUND: A timely risk assessment is desired to guide decisions on preventive
      transfusion safety measures during emerging infectious disease (EID) outbreaks.
      The European Up-Front Risk Assessment Tool (EUFRAT) model was developed to
      provide quantitative transmission risk estimates of EIDs through blood
      transfusion. STUDY DESIGN AND METHODS: The generic model comprises five
      sequential steps to estimate the infection risks in the blood transfusion chain:
      1) the prevalence of infection in the donor population, 2) the risk of obtaining
      infected donations, 3) infected components, 4) infected blood products, and 5)
      the risk of transmitting the infection to recipients. The model uses inputs from
      epidemiologic characteristics of an EID and transfusion practice. The model was
      applied to data from a recent chikungunya outbreak in Italy. RESULTS: Based on
      data from the outbreak peak, an estimated prevalence of 1.07 (95% confidence
      interval [CI], 0.38-2.03) per 100,000 donors would lead to 0.04 infected
      donations (95% CI, 0.01-0.10), 0.13 infected blood components, 0.13 infected end
      products, and 0.0001 severe infections in recipients. This estimated risk can be
      reduced by increasing the duration of quarantine of the donated blood and becomes
      zero after 7 or more days of quarantine. The model also estimated the probability
      of a donor returning from the outbreak area and subsequently donating infected
      blood in his home country to be 0.30 (95% CI, 0.01-0.65) per 100,000. CONCLUSION:
      The model can be used to quantify EID outbreak risks to blood transfusion
      recipients and the effect of targeted safety interventions and as such support
      public health decision-making.

PMID- 23113824
TI  - A diagonal approach to building primary healthcare systems in resource-limited
      settings: women-centred integration of HIV/AIDS, tuberculosis, malaria, MCH and
      NCD initiatives.

PMID- 23113825
TI  - Sorption of chromium with struvite during phosphorus recovery.
AB  - Struvite (MgNH(4)PO(4).6H(2)O; MAP) precipitation is a viable means of phosphorus
      (P) recovery from animal and human wastes. The behavior of metal contaminants
      such as chromium (Cr) during struvite precipitation, however, requires
      consideration. Here the influence of both Cr concentration and oxidation state on
      sorption is assessed. The Cr content of struvite precipitated in the presence of
      1-100 MUM Cr as Cr(III) (22.3-3030.1 mg/kg) was higher than that of solids from
      Cr(VI) (4.5-5.1 mg/kg) solutions. For 1-20 MUM Cr(III) solids, scanning electron
      microscopy (SEM) revealed etch pit formation on struvite crystal surfaces,
      indicative of a surface interaction. The formation of an adsorbate was confirmed
      by X-ray absorption fine structure spectroscopy (XAFS). At initial concentrations
      >=20 MUM Cr(III), XAFS confirmed the formation of a Cr(OH)(3).nH(2)O(am)
      precipitate. Fourier transform infrared (FT-IR) spectroscopy revealed that both
      Cr(III) and Cr(VI) sorption resulted in distortion of the PO(4)(3-) tetrahedra in
      the mineral structure. This, combined with SEM results revealed that even at low
      sorbed concentrations, the Cr impurity can affect the mineral surface and
      structure. Thus, the initial Cr concentration and oxidation state in wastes
      targeted for P recovery will dictate the final Cr content, the mechanism of
      sorption, and impact on the struvite structure.

PMID- 23113826
TI  - A prospective study of pregnancy weight gain in Australian women.
AB  - BACKGROUND: While weight gain during pregnancy is regarded as important, there
      has not been a prospective study of measured weight gain in pregnancy in
      Australia. This study aimed to prospectively evaluate pregnancy-related weight
      gain against the Institute of Medicine (IOM) recommendations in women receiving
      antenatal care in a setting where ongoing weight monitoring is not part of
      routine clinical practice, to describe women's knowledge of weight gain
      recommendations and to describe the health professional advice received relating
      to gestational weight gain (GWG). METHODS: Pregnant women were recruited <=20
      weeks of gestation (n = 664) from a tertiary obstetric hospital between August
      2010 to July 2011 for this prospective observational study. Outcome measures were
      weight gain from pre-pregnancy to 36 weeks of gestation, weight gain knowledge
      and health professional advice received. RESULTS: Thirty-six percent of women
      gained weight according to guidelines. Twenty-six percent gained inadequate
      weight, and 38% gained excess weight. Fifty-six percent of overweight women
      gained weight in excess of the IOM guidelines compared with 30% of those who
      started with a healthy weight (P < 0.001). At 16 weeks, 47% of participants were
      unsure of the weight gain recommendations for them. Sixty-two percent of women
      reported that the health professionals caring for them during this pregnancy
      'never' or 'rarely' offered advice about how much weight to gain. CONCLUSIONS:
      The prevalence of inappropriate gestational weight gain in this study was high.
      The majority of women do not know their recommended weight gain. The advice women
      received from health professionals relating to healthy weight gain in pregnancy
      could be improved.

PMID- 23113827
TI  - Length of stay after reaching clinical stability drives hospital costs associated
      with adult community-acquired pneumonia.
AB  - BACKGROUND: Community-acquired pneumonia (CAP) has a considerable clinical and
      economic impact. The aim of this study was to identify drivers of hospital costs
      associated with CAP in 2 Belgian hospitals. Specifically, the influence of
      patient characteristics, quality indicators, and other treatment aspects on
      hospital costs was explored. METHODS: The following were registered for patients
      admitted with a confirmed diagnosis of CAP in a large university hospital
      (Universitaire Ziekenhuizen Leuven, UZL) and a medium-sized secondary care
      hospital (Ziekenhuis Oost-Limburg, ZOL) in Belgium: the pneumonia severity index
      (PSI), time to clinical stability, length of stay, antibiotic therapy, outcomes,
      compliance with validated quality indicators, and the different costs (pharmacy,
      laboratory, and radiology, and total). Regression analysis was used to identify
      influential variables. RESULTS: Between October 2007 and June 2010, 803 patients
      were included, with a median total cost of ?4794.57. The length of stay after
      clinical stability and time to clinical stability had the highest influence on
      the total cost (+6.3% and +4.9% per additional day, respectively; p < 0.0001).
      Other important drivers of higher costs were total therapy duration, PSI score,
      age, and admission to intensive care. Patients treated with moxifloxacin had
      significantly, but limited, lower costs. Quality indicator compliance, including
      guideline-compliant antibiotic treatment and therapy streamlining, had little
      influence. CONCLUSIONS: The most important driver of hospital costs associated
      with CAP was the time between clinical stability and actual hospital discharge.
      In order to substantially decrease the costs of CAP treatment, this period should
      be rigorously evaluated for possible intervention targets that would allow costs
      in CAP treatment to be decreased in a substantial manner.

PMID- 23113828
TI  - The contraceptive vaginal ring, NuvaRing((r)), a decade after its introduction.
AB  - OBJECTIVES: To review the clinical experience with the contraceptive vaginal ring
      (CVR, NuvaRing((r))) since its introduction over ten years ago. METHODS: The
      literature was searched on efficacy, cycle control, safety, user preference and
      satisfaction of the CVR in comparison with combined oral contraceptives (COCs)
      and the patch, with special attention to recent developments. RESULTS: The ring
      has the same working mechanism and contraindications as COCs. Serum levels of
      steroids are steadier, whereas oestrogenic exposure is lower. Contraceptive
      efficacy is similar, as are metabolic changes. Cycle control is better, and
      compliance and continuation rates are equal or higher. Oestrogen-related adverse
      symptoms appear to be fewer, but reports on the incidence of venous thrombosis
      are conflicting. Expulsion of the ring is reported by 4% to 20% of women. Local
      adverse events are the main reason for discontinuation. Acceptability is as high
      as with COCs and, after structured counselling, the ring is preferred by many
      women to the pill or the patch. CONCLUSIONS: Efficacy of the CVR, and the
      metabolic changes and adverse events it elicits, are generally comparable to
      those of COCs, yet oestrogenic exposure is lower and cycle control superior.
      After counselling, the ring is preferred to the pill by many women.

PMID- 23113830
TI  - The influence of the antiandrogen 2-hydroxyflutamide on the androgen receptor
      expression in the porcine ovarian follicles - an in vitro study.
AB  - Androgens are one of the most important agents influencing ovarian follicles
      growth and development. The biological action of androgens is primarily exerted
      through transcriptional regulation by the androgen receptor (AR), a member of the
      steroid hormone receptor superfamily. The purpose of this study was to test the
      role of androgen receptor agonist testosterone (T) or antagonist 2
      hydroxyflutamide (2-Hf) and in combination on AR expression in cultured porcine
      granulosa cells (GC) or whole follicles. Granulosa cells isolated from mature pig
      follicles were cultured for 48 h. During the last 12 and 24 h of culture, they
      were incubated in the presence of T (10(-7)  m/ml), 2-Hf (1.7 * 10(-4)  m) or
      both T and 2-Hf (T + 2-Hf, at the same concentrations as when added separately).
      To better imitate in vivo conditions, whole follicles (6-8 mm in diameter)
      isolated from porcine ovaries have been incubated (for 12 and 24 h) in an organ
      culture system with the addition of the same factors. Thereafter, cells or
      sections obtained from cultured follicles were processed for AR detection by
      immunocytochemistry or immunohistochemistry. Moreover, expression of AR mRNA and
      protein was determined by real-time PCR and Western blot analysis. It was shown
      that the addition of 2-Hf in the presence of T had a positive effect on AR mRNA
      and protein expression in porcine GC and ovarian follicles. Moreover, the
      addition of 2-Hf influenced AR distribution in GC cultures which is seen as
      change of its localization from nuclear to perinuclear. Our results suggest that
      androgens acting through AR could be involved in the control of AR expression in
      porcine GC in vitro and in vivo.

PMID- 23113829
TI  - Increased hepatitis C virus vaccine clinical trial literacy following a brief
      intervention among people who inject drugs.
AB  - INTRODUCTION AND AIMS: While people who inject drugs are at high risk of
      hepatitis C virus (HCV) infection and will be the target population for future
      HCV vaccine trials, little is known about clinical trial literacy (CTL) in this
      group. We assessed the impact of a brief intervention (BI) designed to improve
      HCV vaccine CTL among people who inject drugs in Sydney, Australia. DESIGN AND
      METHODS: People who inject drugs enrolled in a community-based prospective
      observational study between November 2008 and September 2010 (n = 102) completed
      a CTL assessment followed immediately by the BI. Post-test assessment was
      conducted at 24 weeks. RESULTS: The median age of the sample was 27 years, 73%
      were male and 60% had 10 or less years of schooling. The median time since first
      injection was 5 years and 20% reported daily or more frequent injecting. The mean
      number of correct responses increased from 5.3 to 6.3/10 (t = -4.2; 101df, P <
      0.001) 24 weeks post-intervention. Statistically significant differences were
      observed for three knowledge items with higher proportions of participants
      correctly answering questions related to randomisation (P = 0.002), blinding (P =
      0.005) and vaccine-induced seropositivity (P = 0.003) post-intervention.
      DISCUSSION AND CONCLUSIONS: A significant increase in HCV vaccine CTL was
      observed, suggesting that new and relatively novel concepts can be learned and
      recalled in this group. These findings support the feasibility of future trials
      among this population. [Correction added on 21 November 2012, after first online
      publication: T-score for mean number of correct responses was corrected to '-4.2'
      in the Results section.]

PMID- 23113831
TI  - Unique structures of organelles observed in primary spermatocytes after micro
      injection of protein solutions such as immunoglobulin into the lumen of the
      seminiferous tubules in mice and rats.
AB  - Unique membranous structures of intracytoplasmic organelle, sting of a stack of a
      few flat cisternae about 50 nm in thickness, were found in mouse and rat
      spermatocytes after micro-injection of immunoglobulin G into the lumina of the
      seminiferous tubules. Other proteins such as BSA and cytochrome c used in this
      study also induced the structures. In most cases, the stacks of cisternae were
      rolled up like cigars or cylinders. The structures varied in length and diameter,
      the largest one observed in this study being 10.7 MUm in length. The structures
      did not appear when the testes were fixed just after micro-injection and were
      formed transiently: they were observed in the spermatocytes fixed between 1 and 4
      h after injection. Cytochrome c, micro-injected as an inter-cellular tracer, was
      visualised by a diaminobenzidine reaction. As the reaction product was not
      contained in the cisternae of the unique structures, the lumen of the cisternae
      of the organelles was not continuous with the inter-cellular space. A flocculent
      material of low density was observed in the cisternae of the organelle. Similar
      material was observed in the lumina of solitary cisternae of the rough
      endoplasmic reticulum in the spermatocytes, suggesting that the structures
      derived from endoplasmic reticulum. 

PMID- 23113832
TI  - Medicare's enduring struggle to define "reasonable and necessary" care.
AB  - Medicare legislation mandates that the program not pay for items and services
      that are not "reasonable and necessary" - terms that are open to interpretation
      and easily politicized. In today's fiscal environment, "reasonable and necessary"
      warrants a closer look.

PMID- 23113833
TI  - Atorvastatin with or without an antibody to PCSK9 in primary
      hypercholesterolemia.
AB  - BACKGROUND: Serum proprotein convertase subtilisin/kexin 9 (PCSK9) binds to low
      density lipoprotein (LDL) receptors, increasing the degradation of LDL receptors
      and reducing the rate at which LDL cholesterol is removed from the circulation.
      REGN727/SAR236553 (designated here as SAR236553), a fully human PCSK9 monoclonal
      antibody, increases the recycling of LDL receptors and reduces LDL cholesterol
      levels. METHODS: We performed a phase 2, multicenter, double-blind, placebo
      controlled trial involving 92 patients who had LDL cholesterol levels of 100 mg
      per deciliter (2.6 mmol per liter) or higher after treatment with 10 mg of
      atorvastatin for at least 7 weeks. Patients were randomly assigned to receive 8
      weeks of treatment with 80 mg of atorvastatin daily plus SAR236553 once every 2
      weeks, 10 mg of atorvastatin daily plus SAR236553 once every 2 weeks, or 80 mg of
      atorvastatin daily plus placebo once every 2 weeks and were followed for an
      additional 8 weeks after treatment. RESULTS: The least-squares mean (+/-SE)
      percent reduction from baseline in LDL cholesterol was 73.2+/-3.5 with 80 mg of
      atorvastatin plus SAR236553, as compared with 17.3+/-3.5 with 80 mg of
      atorvastatin plus placebo (P<0.001) and 66.2+/-3.5 with 10 mg of atorvastatin
      plus SAR236553. All the patients who received SAR236553, as compared with 52% of
      those who received 80 mg of atorvastatin plus placebo, attained an LDL
      cholesterol level of less than 100 mg per deciliter, and at least 90% of the
      patients who received SAR236553, as compared with 17% who received 80 mg of
      atorvastatin plus placebo, attained LDL cholesterol levels of less than 70 mg per
      deciliter (1.8 mmol per liter). CONCLUSIONS: In a randomized trial involving
      patients with primary hypercholesterolemia, adding SAR236553 to either 10 mg of
      atorvastatin or 80 mg of atorvastatin resulted in a significantly greater
      reduction in LDL cholesterol than that attained with 80 mg of atorvastatin alone.
      (Funded by Sanofi and Regeneron Pharmaceuticals; ClinicalTrials.gov number,
      NCT01288469.).

PMID- 23113834
TI  - The insurance value of Medicare.
AB  - Medicare should provide access to care and protection from catastrophic spending
      while not being so generous that beneficiaries overconsume low-value care, thus
      driving up costs. Setting cost sharing is a balancing act that the Medicare
      program doesn't perform very well.

PMID- 23113837
TI  - Stereoselectivity of additions to N-methyl acetonitrilium fluorosulfonate.
AB  - Alkoxy-N-methyl-acetiminium salts were prepared by addition of CH3OH and C2H5OH
      to N-methyl acetonitrilium fluorosulfonate at low temperature. Analysis of the
      5J(HH) and 3J(13C-H) coupling constants in the NMR spectra showed an anti
      addition with a diastereoselectivity of >95%. Deprotonation of these salts with
      (Z)-configuration gave the corresponding N-methyl-alkoxyacetimines with very high
      (E)-configuration. Upon protonation at -78  degrees C, these iminoesters gave the
      corresponding alkoxy-N-methyl-acetiminium salts with (E)-configuration.
      Computational analyses of the iminoesters and the corresponding iminium cations
      including the conformations give insight into the relative stability. Nitrilium
      salts can be used as reagents, exemplified by some esterifications between simple
      acids and alcohols.

PMID- 23113836
TI  - Evaluating Helping Babies Breathe: training for healthcare workers at hospitals
      in Rwanda.
AB  - AIM: To evaluate the educational effectiveness of the Helping Babies Breathe
      programme. METHODS: Knowledge of trainees from two district hospitals and one
      tertiary referral hospital was evaluated before and after training in 2010. A
      postcourse practical skills evaluation was performed on a Neonatalie Newborn
      Simulator. Participants underwent a re-evaluation after 3 months. RESULTS: One
      hundred eighteen trainees completed the course. The percentages of correct
      answers on a written test significantly increased from 77 +/- 15% to 91 +/- 9% (p
      < 0.01) after training. The mean score obtained on a postcourse skill evaluation
      was 89 +/- 9%; 64% of the trainees achieved passing scores. Retesting 3 months
      later showed that knowledge remained at the same level, while practical skills
      decreased to 83 +/- 16%, and the pass rate dropped significantly to 43% (p <
      0.01). CONCLUSION: Healthcare workers who participate in a Helping Babies Breathe
      programme can significantly improve their knowledge. While such knowledge is
      retained for at least 3 months, skills dropped to unsatisfactory levels in that
      period of time, indicating the need for retraining in the interim or the
      acquisition of practical experience by such healthcare workers.

PMID- 23113838
TI  - Electronic transport and Raman scattering in size-controlled nanoperforated
      graphene.
AB  - We demonstrate the fabrication and study of the structure-property relationships
      of large-area (>1 cm(2)) semiconducting nanoperforated (NP) graphene with tunable
      constriction width (w = 7.5-14 nm), derived from CVD graphene using block
      copolymer lithography. Size-tunable constrictions were created while minimizing
      unintentional doping by using a dual buffer layer pattern-transfer method. An
      easily removable polymeric layer was sandwiched between an overlying silicon
      oxide layer and the underlying graphene. Perforation-size was controlled by
      overetching holes in the oxide prior to pattern transfer into graphene while the
      polymer protected the graphene from harsh conditions during oxide etching and
      lift off. The processing materials were removed using relatively mild solvents
      yielding the clean isolation of NP graphene and thereby facilitating Raman and
      electrical characterization. We correlate the D to G ratio as a function of w and
      show three regimes depending on w relative to the characteristic Raman relaxation
      length. Edge phonon peaks were also observed at 1450 and 1530 cm(-1) in the
      spectra, without the use of enhancement methods, due to high density of
      nanoconstricted graphene in the probe area. The resulting NP graphene exhibited
      semiconducting behavior with increasing ON/OFF conductance modulation with
      decreasing w at room temperature. The charge transport mobility decreases with
      increasing top-down reactive ion etching. From these comprehensive studies, we
      show that both electronic transport and Raman characteristics change in a
      concerted manner as w shrinks.

PMID- 23113835
TI  - Protease-activated receptor-1 modulates hippocampal memory formation and synaptic
      plasticity.
AB  - Protease-activated receptor-1 (PAR1) is an unusual G-protein coupled receptor
      (GPCR) that is activated through proteolytic cleavage by extracellular serine
      proteases. Although previous work has shown that inhibiting PAR1 activation is
      neuroprotective in models of ischemia, traumatic injury, and neurotoxicity,
      surprisingly little is known about PAR1's contribution to normal brain function.
      Here, we used PAR1-/- mice to investigate the contribution of PAR1 function to
      memory formation and synaptic function. We demonstrate that PAR1-/- mice have
      deficits in hippocampus-dependent memory. We also show that while PAR1-/- mice
      have normal baseline synaptic transmission at Schaffer collateral-CA1 synapses,
      they exhibit severe deficits in N-methyl-d-aspartate receptor (NMDAR)-dependent
      long-term potentiation (LTP). Mounting evidence indicates that activation of PAR1
      leads to potentiation of NMDAR-mediated responses in CA1 pyramidal cells. Taken
      together, this evidence and our data suggest an important role for PAR1 function
      in NMDAR-dependent processes subserving memory formation and synaptic plasticity.

PMID- 23113839
TI  - Interaction of heme proteins with anionic polyfluorene: insights into
      physiological effects, folding events, and inhibition activity.
AB  - Because of the toxicity caused by the heme redox-active iron proteins, their
      elevated levels, localization, and accumulation in the brain, many forms of
      neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and
      Huntington's disease, occur as a result of which the brain becomes vulnerable to
      oxidative stress, ultimately resulting in neuronal death. An anionic water
      soluble conjugated polyfluorene derivative poly(9,9-bis(6-sulfate hexyl) fluorene
      alt-1,4-phenylene) sodium salt (P1) that binds Fe3+ proteins with very high
      selectivity and sensitivity is reported here. The photophysical properties of P1
      were modified by the interaction with ferric heme-containing proteins cytochrome
      c (Cc), methemoglobin (MetHb), and hemin. P1 was found to be highly sensitive
      toward Fe3+ heme proteins as compared to nonmetalloproteins. We observed that the
      respective activities of ferric heme proteins were inhibited and proteins were
      unfolded, due to modification in their heme microenvironment in the presence of
      the polymer P1. The observations reported in this article provide the first
      example for the use of a water-soluble conjugated polymer in applications, such
      as (1) to detect small quantities of iron proteins in aqueous
      medium/physiological condition with the highest K(sv) values of 2.27 * 108 M-1
      for Cc, 3.81 * 107 M-1 for MetHb, and 5.31 * 107 M-1 for hemin; (2) to study the
      physiological effects of heme metalloproteins; (3) to visualize the folding
      events in real time; and (4) the inhibition activity of metalloproteins can be
      selectively studied using a conjugated polymer based assay system rapidly without
      interference from nonmetalloproteins at biological pH. All this is achieved by
      generating optical events, taking advantage of the bright fluorescence of anionic
      polyfluorene P1 in this case, that can be observed and monitored by modification
      in the absorption and emission color in real time.

PMID- 23113840
TI  - Cardiotoxicity, inflammation, and immune response after rattlesnake envenomation
      in the horse.
AB  - BACKGROUND: Cardiac abnormalities are reported in rattlesnake-bitten horses. The
      prevalence and cause are unknown. OBJECTIVES: To detect cardiac damage in
      rattlesnake-bitten horses by measuring cardiac troponin I (cTnI) and evaluating
      ECG recordings for presence of arrhythmias, and explore causes of this cardiac
      damage by measuring venom excretion, anti-venom antibodies, and tumor necrosis
      factor alpha (TNFalpha). ANIMALS: A total of 20 adult horses with a clinical
      diagnosis of rattlesnake bite and 6 healthy adult horses. METHODS: In a
      prospective clinical study, bite site swabs, blood samples, and urine samples
      were collected at various time points from 20 horses with a clinical diagnosis of
      snake bite. Continuous ECG recordings were obtained on the 20 affected horses and
      6 normal control horses using 24-hour holter monitors. Plasma samples were
      assayed for cTnI, serum samples were assayed for TNFalpha and anti-venom
      antibodies, and bite site swabs and urine were assayed for venom. RESULTS: Forty
      percent of rattlesnake-bitten horses (8/20) experienced myocardial damage
      (increased cTnI). Seventy percent (14/20) experienced a cardiac arrhythmia. There
      was a positive correlation between cTnI and TNFalpha (P < .02). Horses with cTnI
      >= 2 ng/mL were more likely to have antibody titers >5,000 (P < .05). No
      correlations were found between venom concentration and cTnI, anti-venom antibody
      titers, TNFalpha, or presence of arrhythmias. CONCLUSIONS AND CLINICAL
      IMPORTANCE: Cardiac abnormalities in this population of horses indicate that
      cardiac damage after rattlesnake bite is common. Rattlesnake-bitten horses should
      be monitored for signs of cardiac damage and dysfunction. Long-term follow-up
      should be encouraged to detect delayed cardiac dysfunction.

PMID- 23113841
TI  - Does MBL2 codon 54 polymorphism play a role in the pathogenesis of psoriasis?
AB  - BACKGROUND: Psoriasis is a T cell-mediated immune disease in which various
      cytokines, primarily tumor necrosis factor-alpha (TNF-alpha), are complexly
      involved. Mannose-binding lectin (MBL) gene polymorphisms decrease MBL serum
      levels, thereby increasing the synthesis of proinflammatory cytokines such as TNF
      alpha. OBJECTIVES: This trial was designed to evaluate the role of the MBL2 codon
      54 polymorphism in the pathogenesis of psoriasis. METHODS: Fifty patients
      diagnosed with psoriasis vulgaris and 53 healthy subjects were included in the
      trial. The polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP) method was applied to determine the MBL2 codon 54 polymorphism.
      Genotypes were determined according to the bands formed in agarose
      electrophoresis gels. For the statistical analysis, the level of significance was
      set at P < 0.05. RESULTS: A total of 33 (66.0%) of the 50 psoriasis patients were
      detected to have A/A genotype and 17 (34.0%) had B/B genotype. Of the control
      subjects, 44 (83.0%) had A/A genotype and nine (17.0%) had B/B genotype. There
      was a statistically significant difference between the groups (P = 0.047). The
      analysis of allele frequencies revealed A allele prevalences to be 79 (79.0%) and
      95 (89.6%), and B allele prevalences to be 21 (21.0%) and 11 (10.4%), in the
      patient and control groups, respectively. A statistically significant difference
      between allele frequencies was detected (P = 0.031). CONCLUSIONS: This study
      suggests that the MBL2 codon 54 polymorphism may have an association with
      psoriasis in the Turkish population.

PMID- 23113842
TI  - Computational modelling of electrocardiograms: repolarisation and T-wave polarity
      in the human heart.
AB  - For more than a century, electrophysiologists, cardiologists and engineers have
      studied the electrical activity of the human heart to better understand rhythm
      disorders and possible treatment options. Although the depolarisation sequence of
      the heart is relatively well characterised, the repolarisation sequence remains a
      subject of great controversy. Here, we study regional and temporal variations in
      both depolarisation and repolarisation using a finite element approach. We
      discretise the governing equations in time using an unconditionally stable
      implicit Euler backward scheme and in space using a consistently linearised
      Newton-Raphson-based finite element solver. Through systematic parameter
      sensitivity studies, we establish a direct relation between a normal positive T
      wave and the non-uniform distribution of the controlling parameter, which we have
      termed refractoriness. To establish a healthy baseline model, we calibrate the
      refractoriness using clinically measured action potential durations at different
      locations in the human heart. We demonstrate the potential of our model by
      comparing the computationally predicted and clinically measured depolarisation
      and repolarisation profiles across the left ventricle. The proposed framework
      allows us to explore how local action potential durations on the microscopic
      scale translate into global repolarisation sequences on the macroscopic scale. We
      anticipate that our calibrated human heart model can be widely used to explore
      cardiac excitation in health and disease. For example, our model can serve to
      identify optimal pacing sites in patients with heart failure and to localise
      optimal ablation sites in patients with cardiac fibrillation. 

PMID- 23113843
TI  - The kinetics and folding pathways of intramolecular G-quadruplex nucleic acids.
AB  - The folding kinetics of G-quadruplex forming sequences is critical to their
      capacity to influence biological function. While G-quadruplex structure and
      stability have been relatively well studied, little is known about the kinetics
      of their folding. We employed a stopped-flow mixing technique to systematically
      investigate the potassium-dependent folding kinetics of telomeric RNA and DNA G
      quadruplexes and RNA G-quadruplexes containing only two G-quartets formed from
      sequences r[(GGA)(3)GG] and r[(GGUUA)(3)GG]. Our findings suggest a folding
      mechanism that involves two kinetic steps with initial binding of a single K(+),
      irrespective of the number of G-quartets involved or whether the G-quadruplex is
      formed from RNA or DNA. The folding rates for telomeric RNA and DNA G
      quadruplexes are comparable at near physiological [K(+)] (90 mM) (tau = ~60 ms).
      The folding of a 2-quartet RNA G-quadruplex with single nucleotide A loops is
      considerably slower (tau = ~700 ms), and we found that the time required to fold
      a UUA looped variant (tau > 100 s, 500 mM K(+)) exceeds the lifetimes of some
      regulatory RNAs. We discuss the implications of these findings with respect to
      the fundamental properties of G-quadruplexes and their potential functions in
      biology.

PMID- 23113844
TI  - Mineral evolution and processes of ferruginous microbialite accretion - an
      example from the Middle Eocene stromatolitic and ooidal ironstones of the
      Bahariya Depression, Western Desert, Egypt.
AB  - Peritidal ferruginous microbialites form the main bulk of the Middle Eocene
      ironstone deposits of the Bahariya Depression, Western Desert, Egypt. They
      include ferruginous stromatolites and microbially coated grains (ferruginous
      oncoids and ooids). Their internal structures reveal repeated cycles of microbial
      and Fe oxyhydroxide laminae. The microbial laminae consist of fossilised
      neutrophilic filamentous iron-oxidising bacteria. These bacteria oxidised the
      Fe(II)-rich acidic groundwater upon meeting the marine water at an approximately
      neutral pH. The iron oxyhydroxide laminae were initially precipitated as
      amorphous iron oxhydroxides and subsequently recrystallised into nanocrystalline
      goethite during early diagenesis. Organic remains such as proteinaceous
      compounds, lipids, carbohydrates and carotenoids are preserved and can be
      identified by Raman spectroscopy. The ferruginous microbialites were subjected to
      post-depositional subaerial weathering associated with sea-level retreat and
      subsurface alteration by continued ascent of the Fe(II)-rich acidic groundwater.
      At this stage, another iron-oxidising bacterial generation prevailed in the
      acidic environment. The acidity of the groundwater was caused by oxidation of
      pyrite in the underlying Cenomanian Bahariya formation. The positive iron
      isotopic ratios and presence of ferrous and ferric iron sulphates may result from
      partial iron oxidation along the redox boundary in an oxygen-depleted
      environment.

PMID- 23113845
TI  - Radiologic and endoscopic characteristics of laparoscopic antireflux wrap:
      correlation with outcome.
AB  - After antireflux surgery for gastroesophageal reflux disease, 10% to 15% of
      patients may have unsuccessful results as a result of abnormal restoration of the
      esophagogastric junction. The purpose of this study was to evaluate the
      postoperative endoscopic and radiologic characteristics of the antireflux barrier
      and their correlation with the postoperative results. After surgery, endoscopic
      and radiologic features of the antireflux wrap were evaluated in 120 consecutive
      patients. Jobe's classification of the postoperative valve was used for the
      definition of a "normal" or "defective" wrap. Patients were evaluated 3 to 5
      years later in order to determine the clinical and objective failed
      fundoplication. A "normal" antireflux wrap was associated with successful results
      in 81.7% of the patients. On the contrary, defective radiologic or endoscopic
      antireflux wrap was observed in 19% of cases. Among these patients, hypotensive
      lower esophageal sphincter was observed in 50% to 65% of patients, abnormal 24
      hour pH monitoring in 91%, and recurrent postoperative erosive esophagitis in 50%
      of patients, respectively (P < 0.001). "Defective" antireflux fundoplication is
      associated with recurrent reflux symptoms, presence of endoscopic esophagitis,
      hypotensive lower esophageal sphincter, and abnormal acid reflux.

PMID- 23113846
TI  - Preoperative ambulatory inspiratory muscle training in patients undergoing
      esophagectomy. A pilot study.
AB  - A major decline in pulmonary function is observed on the first day after upper
      abdominal surgery. This decline can reduce vital and inspiratory capacity and can
      culminate in restrictive lung diseases that cause atelectasis, reduced diaphragm
      movement, and respiratory insufficiency. The objective of this study was to
      evaluate the efficacy of preoperative ambulatory respiratory muscle training in
      patients undergoing esophagectomy. The sample consisted of 20 adult patients (14
      men [70%] and 6 women [30%]) with a diagnosis of advanced chagasic megaesophagus.
      A significant increase in maximum inspiratory pressure was observed after
      inspiratory muscle training when compared with baseline values (from -55.059 +/-
      18.359 to -76.286 +/- 16.786). Preoperative ambulatory inspiratory muscle
      training was effective in increasing respiratory muscle strength in patients
      undergoing esophagectomy and contributed to the prevention of postoperative
      complications.

PMID- 23113847
TI  - Home treatment of uncomplicated acute diverticulitis.
AB  - Diverticular disease of the colon is a common disease, mainly in the population
      over 50 years of age. In acute forms of presentation, we considered home
      treatment in those patients that were classified as having uncomplicated forms by
      means of clinical presentation and a computed tomography of the abdomen.
      According to these criteria, we treated 38 patients at home and admitted 18
      patients to the hospital during the same period of time. No severe complications
      developed in the home-treatment patients. Home treatment is an effective
      alternative treatment for patients with uncomplicated acute diverticulitis. In
      uncomplicated acute diverticulitis, home treatment benefits the patient, over
      hospitalization, by allowing better management of resources and by keeping the
      patient in a familiar environment where there is no risk of a nosocomial
      infection.

PMID- 23113848
TI  - Clinical outcomes after restorative proctocolectomy with ileal pouch anal
      anastomosis using ultrasonically activated scalpel for ulcerative colitis.
AB  - We compared 3 different initial operative procedures performed in patients with
      ulcerative colitis who underwent an ileal pouch anal anastomosis (IPAA) procedure
      with a Harmonic Scalpel (HS). We selected 775 patients who underwent a
      restorative proctocolectomy with a mucosectomy using an HS and hand-sewn IPAA.
      Ninety-six patients underwent a total colectomy (3-stage procedure) as the
      initial operation, whereas 258 underwent IPAA without ileostomy (1-stage
      procedure) and 421 underwent IPAA with ileostomy (2-stage procedure). There were
      no significant differences regarding early pouch functional rate among the 3
      groups. After 5 years with a functioning ileal pouch, the survival rates for the
      total colectomy, IPAA with ileostomy, and IPAA without ileostomy groups were
      100%, 99.3%, and 99.0%, respectively. There was low operative mortality, and
      acceptable rates of early and late complications in patients with ulcerative
      colitis who underwent a restorative proctocolectomy and IPAA using an HS.

PMID- 23113849
TI  - Colorectal cancer treatment and follow-up in the elderly: an inexplicably
      different approach.
AB  - The incidence of colorectal cancer increases as age progresses. At present,
      elderly patients have received substandard cancer treatment not supported by
      "evidence." Geriatric assessment should be performed preoperatively and selected
      elderly patients must be offered standard surgical treatment receiving the same
      complementary therapies as a younger patient. It should be stressed that elderly
      patients should not be deprived of their decision-making role. In our experience,
      more than 43% of patients with colorectal cancer are >=70 years of age, and we
      believe that they should receive the same type of follow-up. This would allow for
      the detection and removal of polyps, treatment of malignant tumors, and
      psychological support similarly to younger patients. Significantly, in our
      experience, the incidence of reoperation for neoplastic disease is similar in the
      two patient populations.

PMID- 23113850
TI  - Pilonidal sinus disease: risk factors for postoperative complications and
      recurrence.
AB  - The aim of this study is to analyze the risk factors for complications and
      recurrence in pilonidal sinus disease. The prospective study consisted of 144
      patients with pilonidal sinus disease who were operated on at Dicle University
      Medical Faculty, Department of General Surgery, between February 2008 and
      December 2010. Patients receiving the Limberg flap totaled 106 (73.6%), while 38
      (26.4%) had primary closure. Postoperative complications developed in 42 subjects
      (29.2%), and recurrence occurred in 19 (13.2%). The Limberg flap method was
      statistically considered as a risk factor for postoperative complications (P  = 
      0.039). Regarding recurrence, family tendency (P  =  0.011), sinus number (P  = 
      0.005), cavity diameter (P  =  0.002), and primary closure (P  =  0.001) were
      found to be risk factors. Postoperative complication rate is higher in the
      Limberg flap method than primary closure method. The risk of recurrence is
      related to family tendency, sinus number, cavity diameter and anesthesia type and
      is also higher in primary closure.

PMID- 23113851
TI  - A case of hepatocellular carcinoma with portal vein tumor thrombosis successfully
      treated by a combination of intra-arterial infusion 5-fluorouracil, cisplatin,
      and systemic interferon-alpha therapies.
AB  - A 58-year-old female with hepatitis C was referred to our hospital after computed
      tomography (CT) revealed a tumor in the right lobe of her liver. After thorough
      examination, tumor thrombosis was detected on the main trunk of the portal vein,
      and we decided to administer a combination of subcutaneous interferon-alfa and
      intra-arterial 5-fluorouracil. However, after 2 cycles of treatment, this regimen
      was ineffective, and thus cisplatin (CDDP) was added for the third cycle. On
      completion of 5 treatment cycles, the tumor and portal vein tumor thrombosis were
      not detected by CT or (18)F-2-fluoro-2-deoxy-D-glucose positron emission
      tomography. Hence, chemotherapy was considered effective and stopped. Two years
      after chemotherapy, Alpha-fetoprotein (AFP) and protein induced by vitamin K
      absence or antagonists-II (PIVKA-II) levels were within normal limits.
      Combination therapies have been recognized recently, and judging from the above
      case, the addition of CDDP to the combination regimen can prove beneficial.

PMID- 23113852
TI  - Torsion of the gallbladder diagnosed by magnetic resonance
      cholangiopancreatography.
AB  - Torsion of the gallbladder is a rare entity that is difficult to diagnose
      preoperatively, the principal differential diagnosis being cholecystitis. The
      condition occurs most often in the elderly. Although its etiology is unknown, the
      presence of a redundant mesentery is a prerequisite for torsion. Computed
      tomography, ultrasound, and magnetic resonance cholangiopancreatography can
      provide important diagnostic clues. Torsion of the gallbladder occurs when it
      twists axially, with subsequent occlusion of bile or blood flow. Therefore,
      prompt surgical treatment is necessary in order to prevent necrosis and
      perforation. In the present study, we report a case of torsion of the gallbladder
      diagnosed by magnetic resonance cholangiopancreatography. This condition was
      successfully treated by laparoscopic cholecystectomy.

PMID- 23113853
TI  - Liver hydatid cyst rupture into the peritoneal cavity after abdominal trauma:
      case report and literature review.
AB  - The aim of this study was to review the literature regarding the rupture of
      hydatid cysts into the abdominal cavity after trauma. We present both a new case
      of hydatid cyst rupture that occurred after blunt abdominal trauma and a
      literature review of studies published in the English language about hydatid cyst
      rupture after trauma; studies were accessed from PubMed, Google Scholar, EBSCO,
      EMBASE, and MEDLINE databases. We identified 22 articles published between 2000
      and 2011 about hydatid cyst rupture after trauma. Of these, 5 articles were
      excluded because of insufficient data, duplication, or absence of intra-abdominal
      dissemination. The other 17 studies included 68 patients (38 males and 30
      females) aged 8 to 76 years who had a ruptured hydatid cyst detected after
      trauma. The most common trauma included traffic accidents and falls. Despite
      optimal surgical and antihelmintic therapy, 7 patients developed recurrence.
      Complications included biliary fistula in 5 patients, incisional hernia in 2
      patients, and gastrocutaneous fistula in 1 patient. Death occurred from
      intraoperative anaphylactic shock in 1 patient and gastrointestinal bleeding and
      pulmonary failure in 1 patient. Rupture of a hydatid cyst into the peritoneal
      cavity is rare and challenging for the surgeon. This condition is included in the
      differential diagnosis of the acute abdomen in endemic areas, especially in young
      patients.

PMID- 23113854
TI  - Spontaneous intraperitoneal rupture of a hepatic hydatid cyst.
AB  - Hydatid cysts, which are endemic to certain areas, typically are found in the
      liver. Spontaneous intraperitoneal rupture, which can be life threatening, is
      rare. This article presents a case of spontaneous rupture of a hydatid cyst in a
      69-year-old woman who was admitted to the emergency department. The patient had
      no history of trauma. Abdominal ultrasonography and computed tomography suggested
      rupture of a hydatid cyst. The patient underwent a partial cystectomy, and the
      cystic area was washed with hypertonic saline and the peritoneal cavity was
      washed with isotonic saline and drained. Postoperatively, the patient was treated
      with albendazole for 3 months. No additional pathology was observed at the 3-, 6
      , and 9-month follow-ups. Although rare, a ruptured hydatid cyst should be
      considered in the differential diagnosis of the acute abdomen in a patient
      residing in an endemic area.

PMID- 23113855
TI  - A case of diffuse neuronal hypertrophy in acute appendicitis.
AB  - We report a case of neuronal hypertrophy associated with acute appendicitis in
      which significant neuronal fibers and the number of ganglion cells increased in
      the absence of inflammatory cells. Differential diagnosis from diffuse
      ganglioneuromatosis by the pathologic findings of resected specimen was
      difficult. A 33-year-old Japanese female visited our hospital complaining of
      acute abdominal pain. The patient underwent appendectomy upon the diagnosis of
      acute appendicitis on the day of admission. Postoperative examinations found no
      neoplastic lesions in other organs or inherited disorders such as multiple
      endocrine neoplasia (MEN) type 2b and von Recklinghausen's disease (VRD). The
      pathologic diagnosis was neuronal hypertrophy of the appendix. Because the
      clinical outcomes of diffuse ganglioneuromatosis and neuronal hypertrophy of the
      gastrointestinal tract are quite different, clinical and pathologic examination
      should be carefully carried out for lesions in which significant proliferation of
      neuronal components is seen.

PMID- 23113856
TI  - Abdominopelvic actinomycosis associated with an intrauterine device and
      presenting with a rectal mass and hydronephrosis: a troublesome condition for the
      clinician.
AB  - Actinomycosis is an uncommon, chronic, granulomatous disease that can be mistaken
      for a malignant tumor. Abdominopelvic actinomycosis constitutes about 20% of all
      actinomycosis cases and may mimic malignancy, tuberculosis, or other
      abdominopelvic inflammatory diseases. This condition is more prevalent in women
      who use an intrauterine device. We treated a 44-year-old woman who presented with
      vaginal discharge, right flank pain, dysuria, and difficulty with defecation. She
      had anorexia and weight loss (8 kg) during the previous 2 months and had a
      history of intrauterine device use for 12 years. Clinical, radiologic, and
      endoscopic examinations revealed a rectal mass and right hydronephrosis. Rectal
      biopsy showed nonspecific colitis. Laparotomy showed a mass that was invading and
      obstructing the pelvic orifice. Surgery included total abdominal hysterectomy,
      bilateral salpingo-oophorectomy, appendectomy, low anterior resection, and
      Hartmann colostomy. Histopathologic evaluation of surgical specimens showed
      actinomycosis originating from the tubo-ovarian structures and invading the
      rectal wall. The patient was placed on penicillin for 6 months, and then had
      closure of the colostomy with no complication.

PMID- 23113857
TI  - Mesenteric histiocytosis or only an inflammatory infiltration of histiocytes? A
      case report from a surgical point of view.
AB  - The mesenteric sclerosing processes are very rare tumors. There are only a few
      cases of mesenteric fibromatosis described in literature. A case of mesenteric
      histiocytosis or a mesenteric infiltration by histocytes as a reactive
      inflammatory process is not described in the surgical literature. Because of its
      clinical and macroscopic similarity to a fibromatosis or a reactive inflammatory
      process and a lack of articles in the literature on mesenteric histiocytosis we
      concentrated our research in literature on the mesenteric fibromatosis and its
      differential diagnosis.

PMID- 23113858
TI  - Mucocele of the appendix: case report and review of literature.
AB  - Appendiceal mucocele is a rare disease. Sometimes it is discovered accidentally
      and sometimes it resembles acute appendicitis. Correct diagnosis before surgery
      is very important for the selection of adequate surgical treatment to avoid
      intraoperative and postoperative complications. Ultrasonography, and particularly
      computed tomography, should be used extensively for this purpose. If mucocele is
      treated incorrectly pseudomyxoma peritonei, which is characterized by malignant
      process, may develop. We present a case of a 54-year-old man who was admitted to
      the emergency department with the signs of acute appendicitis. Open surgery was
      performed. At the time of surgery, a cystic mass of the appendix with dimensions
      7 * 4 *3 cm, with inflamed walls, but without perforation was discovered in the
      right iliac fossa. No discharge was found in the peritoneal cavity. Diagnosis of
      mucocele was suspected. Only appendectomy was performed because no pathologic
      process was found in the base of the appendix and lymph nodes were not increased
      in size. Hystopathologic diagnosis was mucinous cystadenoma. After 2 years, the
      patient is feeling well.

PMID- 23113859
TI  - Maxillary verrucous carcinoma coincident with cervical lymph node metastasis of
      colon adenocarcinoma.
AB  - Cervical lymph node metastasis is an extremely rare event in oral verrucous
      carcinoma. Isolated cervical lymph node metastasis of colon cancer is also rare.
      This article describes a case of maxillary verrucous carcinoma accompanied by
      colon adenocarcinoma that metastasized to a cervical lymph node in a 69-year-old
      Japanese woman. During preoperative evaluation for maxillary verrucous carcinoma,
      enlarged cervical lymph nodes and colon cancer were suspected by positron
      emission tomography. Colonoscopy with biopsies confirmed primary colon
      adenocarcinoma. Left radical neck dissection, partial maxillectomy, and full
      thickness skin graft to the mucosa of the upper lip were performed before
      treatment of colon adenocarcinoma. Cervical lymph nodes showed metastasis from
      colon adenocarcinoma, and right hemicolectomy was performed. This is the first
      case report of synchronous oral verrucous carcinoma and colon adenocarcinoma with
      cervical lymph node metastasis.

PMID- 23113861
TI  - Editorial.

PMID- 23113860
TI  - Prognosis of patients with gastric cancer who underwent proximal gastrectomy.
AB  - Proximal gastrectomy (PG) has been introduced for patients who are preoperatively
      diagnosed with early gastric cancer located in the upper third of the stomach. In
      the present study, we compared the prognosis of patients who underwent PG with
      that of patients who underwent total gastrectomy (TG). Between 1997 and 2006, 51
      patients were diagnosed with early gastric cancer located in the upper third of
      the stomach and underwent PG. In the same period, 35 patients were diagnosed with
      early gastric cancer and underwent TG. Of these, in 24 patients, the cancer was
      localized in the middle to upper part of the stomach, and 11 patients had
      multiple cancers. We compared the clinicopathologic differences and prognoses
      between the two groups. Significantly fewer lymph nodes were dissected in the PG
      group (mean, 18.2) than in the TG group (mean, 36.6;P < 0.001). Complications
      were detected in 17.6% of patients in the PG group and in 14.3% of patients in
      the TG group, which was not significant (P = 0.678). The overall and disease
      specific 5-year survival rates in the 51 patients who underwent PG (88.7% and
      97.1%, respectively) were not different from those in the 35 patients who
      underwent TG (87.6% and 93.4%; P = 0.971 and P = 0.553; respectively). These
      findings indicate that PG can be performed safely and may have various advantages
      compared with TG in terms of patients' daily lives.

PMID- 23113862
TI  - Effects of genetics and environment on the metabolome of commercial maize
      hybrids: a multisite study.
AB  - This study was designed to elucidate the biological variation in expression of
      many metabolites due to environment, genotype, or both, and to investigate the
      potential utility of metabolomics to supplement compositional analysis for
      substantial equivalence assessments of genetically modified (GM) crops. A total
      of 654 grain and 695 forage samples from 50 genetically diverse non-GM DuPont
      Pioneer maize hybrids grown at six locations in the U.S. and Canada were analyzed
      by coupled gas chromatography time-of-flight-mass spectrometry (GC/TOF-MS). A
      total of 156 and 185 metabolites were measured in grain and forage samples,
      respectively. Univariate and multivariate statistical analyses were employed
      extensively to compare and correlate the metabolite profiles. We show that the
      environment had far more impact on the forage metabolome compared to the grain
      metabolome, and the environment affected up to 50% of the metabolites compared to
      less than 2% by the genetic background. The findings from this study demonstrate
      that the combination of GC/TOF-MS metabolomics and comprehensive multivariate
      statistical analysis is a powerful approach to identify the sources of natural
      variation contributed by the environment and genotype.

PMID- 23113863
TI  - Conversion to enteric-coated mycophenolate sodium from mycophenolate mofetil in
      stable renal transplant patients: results of an Asia-Pacific study.
AB  - AIM: Mycophenolate mofetil has proven efficacy in the prophylaxis of acute
      rejection in solid organ transplantation; however, gastrointestinal intolerance
      can risk this efficacy because of associated dose adjustments and discontinued
      treatment. Enteric-coated mycophenolate sodium has demonstrated improved
      gastrointestinal tolerability, but the data in Asian subjects are scarce.
      METHODS: This was a Phase-IIIb, open-label, single-arm, multicentre, prospective
      6-month study which investigated safety and graft function in stable maintenance
      renal transplant recipients of Asian origin, after switching from mycophenolate
      mofetil to enteric-coated mycophenolate sodium at least 3 months after
      transplantation. Primary end-points included renal allograft function and safety
      parameters. RESULTS: The study recruited patients from 16 centres in Asian
      countries. The intention-to-treat and safety populations both included 122
      patients. Graft function remained stable over the course of the study as measured
      by creatinine clearance and glomerular filtration rate. At 6 months the incidence
      of any gastrointestinal adverse events was 20.5% (n = 25), none of which required
      dose adjustments. There were only three cases of biopsy proven acute rejection
      with no reports of graft loss or death. CONCLUSION: This study demonstrated that
      enteric-coated mycophenolate sodium is a safe and effective alternative to
      mycophenolate mofetil in Asian kidney transplant recipients.

PMID- 23113864
TI  - Elaborating on the construct validity of the Triarchic Psychopathy Measure in a
      criminal offender sample.
AB  - Patrick, Fowles, and Krueger (2009) developed the triarchic conceptualization of
      psychopathy in an effort to integrate historical theories and contemporary
      measurement models. The model proposes 3 phenotypic domains of boldness,
      meanness, and disinhibition. Patrick (2010) developed the Triarchic Psychopathy
      Measure (TriPM), a 58-item self-report measure, to index these 3 domains. This
      study examined the construct validity of the TriPM in a sample of incarcerated
      offenders (N = 141) and found evidence of good construct validity in that the
      scales were related to conceptually relevant normal-range and dysfunctional
      personality trait criteria, as well as narcissism and deficits in empathy.

PMID- 23113865
TI  - The impact of mitochondrial and thermal stress on the bioenergetics and reserve
      respiratory capacity of fish cell lines.
AB  - Various stressors affect the health of wild and cultured fish and can cause
      metabolic disturbances that first manifest at the cellular level. Here, we sought
      to further our understanding of cellular metabolism in fish by examining the
      metabolic responses of cell lines derived from channel catfish Ictalurus puntatus
      (CCO), white bass Morone chrysops (WBE), and fathead minnow Pimephales promelas
      (EPC) to both mitochondrial and thermal stressors. Using extracellular flux (EF)
      technology, we simultaneously measured the oxygen consumption rate (OCR; a
      measure of mitochondrial function) and extracellular acidification rate (ECAR; a
      surrogate of glycolysis) in each cell type. We performed a mitochondrial function
      protocol whereby compounds modulating different components of mitochondrial
      respiration were sequentially exposed to cells. This provided us with basal and
      maximal OCR, OCR linked to ATP production, OCR from ion movement across the
      mitochondrial inner membrane, the reserve capacity, and OCR independent of the
      electron transport chain. After heat shock, EPC and CCO significantly decreased
      OCR and all three cell lines modestly increased ECAR. After heat shock, the
      reserve capacity, the mitochondrial energetic reserve used to cope with stress
      and increased bioenergetic demand, was unaffected in EPC and CCO and completely
      abrogated in WBE. These findings provide proof-of-concept experimental data that
      further highlight the utility of fish cell lines as tools for modeling
      bioenergetics.

PMID- 23113866
TI  - Enhanced reduction of Fe(II)EDTA-NO/Fe(III)EDTA in NO(x) scrubber solution using
      a three-dimensional biofilm-electrode reactor.
AB  - A promising technique called chemical absorption-biological reduction (CABR)
      integrated approach has been developed recently for the nitrogen oxides (NO(x))
      removal from flue gases. The major challenge for this approach is how to enhance
      the rate of the biological reduction step. To tackle the challenge, a three
      dimensional biofilm-electrode reactor (3D-BER) was utilized. This reactor
      provides not only considerable amount of sites for biofilm, but also many
      electron donors for bioreduction. Factors affecting the performance of 3D-BER
      were optimized, including material of the third electrode (graphite), glucose
      concentration (1000 mg.L(-1)), and volume current density (30.53 A.m(-3) NCC).
      Experimental results clearly demonstrated that this method significantly promotes
      the bioreduction rate of Fe(II)EDTA-NO (0.313 mmol.L(-1).h(-1)) and Fe(III)EDTA
      (0.564 mmol.L(-1).h(-1)) simultaneously. Experiments on the mechanism showed that
      Fe(II)EDTA serves as the primary electron donor in the reduction of Fe(II)EDTA
      NO, whereas the reduction of Fe(III)EDTA took advantage of both glucose and
      electrolysis-generated H(2) as electron donors. High concentration of Fe(II)EDTA
      NO or Fe(III)EDTA interferes the bioreduction of the other one. The proposed
      methodology shows a promising prospect for NO(x) removal from flue gas.

PMID- 23113867
TI  - Hemolytic anemia due to passenger lymphocyte syndrome in solid malignancy
      patients treated with allogeneic natural killer cell products.
AB  - BACKGROUND: Allogeneic natural killer (NK) cell products for treatment of solid
      organ malignancies were prepared by performing T (CD3+)-cell depletion on
      nonmobilized apheresis mononuclear cell collections. The products were not B-cell
      depleted. This report details two cases of passenger lymphocyte syndrome (PLS)
      after NK-cell infusion. CASE REPORTS: Patient 1 is a blood group A+ 56-year-old
      female with Stage IV ovarian carcinoma who received NK cells from an O+ donor. On
      day +7 she developed new hemolytic anemia. Direct antiglobulin test (DAT) was
      positive for immunoglobulin G and C3, and the eluate contained anti-A.
      Subsequently, anti-A was identified on reverse typing. She was transfused with
      group O red blood cells (RBCs). By day +12 she forward typed as O with anti-A and
      B on reverse typing. By day +42, DAT was negative with only weak anti-A on
      reverse typing. Patient 2 is a blood group B+ 51-year-old female with metastatic
      lobular breast carcinoma who received NK cells from an O+ donor. On day +7 she
      developed new hemolytic anemia. DAT was positive, and the eluate contained anti-A
      and -B. Anti-A reactivity was due to anti-A,B. The next day she developed new
      anti-B on reverse typing. She was transfused with O RBCs. Anti-B titer increased
      to a maximum of 512 on day +12. At discharge on Day +29 her anti-B titer was
      still 32. CONCLUSIONS: These patients developed PLS after infusion of NK cells.
      Because of these cases NK-cell products are now B (CD19+)-cell depleted at our
      institution, and this approach is recommended for other centers.

PMID- 23113868
TI  - The impact of infection control upon hospital-acquired influenza and respiratory
      syncytial virus.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) and influenza are important
      pediatric community-acquired (CA) and hospital-acquired (HA) pathogens. The
      occurrence of pandemic (H1N1) 2009 influenza resulted in additional efforts to
      intensify infection control (IC) strategies. We detail the impact of IC
      strategies between 2003 and 2010 on influenza and RSV. METHODS: We assessed the
      rates of CA infections per 100 admissions and HA infections per 1000 patient-days
      for both RSV and influenza at Children's Memorial Hospital during the winter
      seasons (September through May) 2003-2010. The season of 2009, however, was
      extended through June due to ongoing admissions as a result of pandemic (H1N1)
      2009 influenza. IC strategies implemented in response to pandemic (H1N1) 2009
      influenza are described. The transmission ratio (HA cases/CA cases) was
      determined and correlated with IC efforts. RESULTS: Substantial season- to-season
      variability exists for CA RSV and CA influenza rates. The rates of HA RSV and HA
      influenza and the transmission ratios for these viruses remained unchanged in
      2009-10 in comparison to the prior year (at 0.02 and 0.01, respectively) despite
      implementation of multiple IC strategies. In contrast, since 2005 an inverse
      association was noted between hand hygiene compliance and the transmission ratio
      of both RSV and influenza, with Spearman correlation coefficients of -0.84 (p =
      0.051) and -0.89 (p = 0.008), respectively. CONCLUSIONS: We observed that
      improvements in hand hygiene compliance correlated with less transmission of RSV
      and influenza in the hospital. The important role of hand hygiene in preventing
      transmission of RSV and influenza to hospitalized children should be emphasized.

PMID- 23113869
TI  - Transient receptor potential channels in bladder function.
AB  - The transient receptor potential (TRP) superfamily of cationic ion channels
      includes proteins involved in the transduction of several physical and chemical
      stimuli to finely tune physiological functions. In the urinary bladder, they are
      highly expressed in, but not restricted to, primary afferent neurons. The
      urothelium and some interstitial cells also express several TRP channels. In this
      review, we describe the expression and the known roles of some members of TRP
      subfamilies, namely TRPV, TRPM and TRPA, in the urinary bladder. The therapeutic
      interest of modulating the activity of TRP channels to treat bladder dysfunctions
      is also discussed.

PMID- 23113870
TI  - Framing global health: the governance challenge.
AB  - With the emergence of global health comes governance challenges which are equally
      global in nature. This article identifies some of the initial limitations in
      analyses of global health governance (GHG) before discussing the focus of this
      special supplement: the framing of global health issues and the manner in which
      this impacts upon GHG. Whilst not denying the importance of material factors
      (such as resources and institutional competencies), the article identifies how
      issues can be framed in different ways, thereby creating particular pathways of
      response which in turn affect the potential for and nature of GHG. It also
      identifies and discusses the key frames operating in global health: evidence
      based medicine, human rights, security, economics and development.

PMID- 23113871
TI  - Risk factors associated with brachial-ankle pulse wave velocity among peritoneal
      dialysis patients in Macao.
AB  - BACKGROUND: Cardiovascular disease is the leading cause of mortality among
      peritoneal dialysis (PD) patients in Macao. Increased arterial stiffness
      determined by pulse wave velocity (PWV) has been established as an independent
      predictor of cardiovascular mortality in end-stage renal disease patients. The
      present study aims to investigate the relationship between arterial stiffness and
      its associated risk factors in chronic PD patients. METHODS: A total of 96
      chronic PD patients (48 males/48 females) were included in the cross-sectional
      study. Arterial stiffness was assessed by brachial-ankle PWV (baPWV). Patients
      were divided into two subgroups according to mean baPWV value. On enrollment,
      clinical characteristics and biochemical parameters were collected. RESULTS:
      Compared with low baPWV group patients, high baPWV group patients were
      significant older (p<0.001) and more likely to have a high proportion of female
      gender (p=0.004) as well as previous CVD history (p=0.008). Serum albumin, pre
      albumin levels and residual renal creatinine clearance (CCr) were significantly
      lower but the serum ferritin level was significantly higher in high baPWV group
      patients than in low baPWV group patients (all p<0.01). BaPWV was positively
      associated with age (r=0.534, p<0.001), Charlson comorbidity index (r=0.350,
      p<0.001) and serum ferritin level (r=0.340, p=0.001). Meanwhile, baPWV negatively
      correlated with serum albumin (r=-0.479, p<0.001), pre-albumin levels (r=-0.320,
      p=0.003) and residual renal CCr (r=-0.177, p=0.048). Age-adjusted partial
      correlation test found a significant correlation between baPWV and CRP (r=0.462,
      p<0.001). Multivariate regression analysis showed that baPWV was independently
      associated with age (p<0.001), serum albumin level (p=0.015), CRP (p=0.019) and
      residual renal CCr (p=0.045). CONCLUSION: Arterial stiffness, assessed by baPWV,
      had an independent correlation with age, serum albumin level, CRP level and
      residual renal CCr among PD patients in Macao.

PMID- 23113873
TI  - Preparing for PrEP.
AB  - Recent studies have shown that in selected conditions antiretroviral drugs can be
      used to protect HIV seronegative persons from becoming infected, when exposed to
      the risk of sexual HIV transmission. This concept of 'pre-exposure prophylaxis'
      or 'PrEP' has raised many questions that concern cost, safety and ethical issues.
      In this article, different aspects of PrEP are analysed with a view to trying to
      answer the question whether today's society is already prepared to accept PrEP as
      one of the tools to prevent transmission of HIV by high-risk sexual contacts.

PMID- 23113872
TI  - Analysis of a unique Clostridium botulinum strain from the Southern hemisphere
      producing a novel type E botulinum neurotoxin subtype.
AB  - BACKGROUND: Clostridium botulinum strains that produce botulinum neurotoxin type
      E (BoNT/E) are most commonly isolated from botulism cases, marine environments,
      and animals in regions of high latitude in the Northern hemisphere. A strain of
      C. botulinum type E (CDC66177) was isolated from soil in Chubut, Argentina.
      Previous studies showed that the amino acid sequences of BoNT/E produced by
      various strains differ by < 6% and that the type E neurotoxin gene cluster
      inserts into the rarA operon. RESULTS: Genetic and mass spectral analysis
      demonstrated that the BoNT/E produced by CDC66177 is a novel toxin subtype (E9).
      Toxin gene sequencing indicated that BoNT/E9 differed by nearly 11% at the amino
      acid level compared to BoNT/E1. Mass spectrometric analysis of BoNT/E9 revealed
      that its endopeptidase substrate cleavage site was identical to other BoNT/E
      subtypes. Further analysis of this strain demonstrated that its 16S rRNA sequence
      clustered with other Group II C. botulinum (producing BoNT types B, E, and F)
      strains. Genomic DNA isolated from strain CDC66177 hybridized with fewer probes
      using a Group II C. botulinum subtyping microarray compared to other type E
      strains examined. Whole genome shotgun sequencing of strain CDC66177 revealed
      that while the toxin gene cluster inserted into the rarA operon similar to other
      type E strains, its overall genome content shared greater similarity with a Group
      II C. botulinum type B strain (17B). CONCLUSIONS: These results expand our
      understanding of the global distribution of C. botulinum type E strains and
      suggest that the type E toxin gene cluster may be able to insert into C.
      botulinum strains with a more diverse genetic background than previously
      recognized.

PMID- 23113874
TI  - The case for retaining severe perineal tears as an indicator of the quality of
      obstetric care.
AB  - BACKGROUND: The incidence of severe perineal tears acquired during vaginal
      childbirth varies considerably across hospitals but its use as a safety and
      quality indicator is in jeopardy because of problems associated with accurate
      detection and recording. AIM: To understand and interpret time trends in the
      incidence of third- and fourth-degree perineal tears among women giving birth
      vaginally in 18 public maternity hospitals in South Australia, taking into
      account individualised risk factors for each birth. METHODS: The risk-adjusted
      probability of a third- and fourth-degree tear was estimated for each of 65,598
      singleton vaginal births (2002-2008), using a previously published regression
      model. The risk factors for each birth included maternal age; parity and
      ethnicity; assistance with instruments and episiotomy; shoulder dystocia; and
      infant birthweight. Plots of 'excess' tears were generated to help identify
      maternity services where the observed incidence of severe trauma differed from
      the expectation estimated from the risk profiles. RESULTS: Three hospitals were
      identified at which there were systematically more tears than expected (given
      their risk profiles), and five hospitals were identified at which there were
      fewer tears. However, increased tearing at two hospitals coincided closely with
      improved advocacy for better detection and treatment of perineal tears
      (especially partial third-degree tears). CONCLUSION: Statistical process control
      methods provide a powerful means of investigating temporal variations in the
      incidence of outcomes like severe perineal tears. Third- or fourth- degree tears
      should be retained as a quality indicator of maternity services, but it is likely
      that many third-degree tears currently go undetected.

PMID- 23113875
TI  - Screening for Y chromosome microdeletions in childhood: lack of evidence for a
      direct association with testicular maldescent.
AB  - The aim of the study was to investigate the hypothesis that Y chromosome
      microdeletions are directly implicated in testicular maldescent. Genomic DNA was
      extracted from the peripheral blood of 292 subjects. This population consisted of
      (i) 180 children with all phenotypes of isolated (non-syndromic) testicular
      maldescent from 174 index families, (ii) affected adult relatives available (n =
      12) and (iii) 100 unrelated children with normal external genitalia (controls).
      The sequence-tagged site primer set and the conditions of conventional polymerase
      chain reaction amplification were based on the current laboratory guidelines for
      molecular diagnosis of Y chromosome microdeletions recommended by the European
      Academy of Andrology and the European Molecular Genetics Quality Network. Two
      multiplex reactions were designed to screen the regions of azoospermic factors a,
      b and c. Each multiplex reaction included adequate internal and external
      amplification controls. Amplification products were submitted to electrophoresis
      on 2% agarose gel impregnated with ethidium bromide dye solution for 80 volt-h
      and visualised under ultraviolet light. No microdeletions were detected in any
      subject. These results indicate that Y chromosome microdeletions are not directly
      implicated in the pathogenesis of testicular maldescent. Other factors should be
      investigated to potentially explain the genetic predisposition that seems to
      exist in at least a subgroup of these patients. 

PMID- 23113876
TI  - Psychometric properties of the Tunisian-Arabic version of the Women's Health
      Questionnaire.
AB  - OBJECTIVES: The Women's Health Questionnaire has been developed for the
      assessment of symptom perception in mid-aged women. It explores a range of
      psychological and physical symptoms and is one of the most used health-related
      quality of life measures. It was developed in the English language and is
      available in several other languages. The aim of this study was to evaluate the
      psychometric properties of the Tunisian-Arabic version of the questionnaire.
      METHODS: A Tunisian-Arabic translation of the original version of the Women's
      Health Questionnaire (36-item WHQ) was produced using the forward-backward
      translation method recommended by the designers. A total of 1231 women were
      anonymously recruited from the general population using the quota method of
      sampling. All women were administered the WHQ as part of a broader questionnaire;
      1150 records were finally retained for analysis. Psychometric evaluation was
      performed for the original version of the WHQ (36 items) and then for the 23-item
      revised version proposed by the MAPI Research Institute. RESULTS: The
      acceptability and comprehensibility of the scale were good. The 36-item version
      showed overall good reliability, but some subscales lacked internal consistency.
      The validity was explored by principal component analysis and showed significant
      differences with the original English instrument and some deficiencies in its
      dimensional structure. The validity of the 23-item revised version was better.
      Finally, we suggest some adjustments to improve the reliability and validity of
      the instrument. CONCLUSION: The Tunisian-Arabic version of the WHQ is globally
      reliable and valid, but we recommend the use of an improved shortened version,
      more specific to mid-aged women.

PMID- 23113877
TI  - Does rectal examination have any value in the clinical diagnosis of cauda equina
      syndrome?
AB  - PURPOSE: This study aims to quantify the value of digital rectal examination
      (DRE) in the clinical diagnosis of cauda equina syndrome. METHODS: A
      retrospective case note review was performed on all patients referred to a
      University Teaching Hospital over a one-year period with documented suspicion of
      cauda equina syndrome. All Patients underwent MRI scanning to either confirm or
      rule out the diagnosis. RESULTS: Fifty-seven such patients were identified, 13
      (23%) of whom had confirmation of cauda equina syndrome on MRI scanning. The DRE
      did not significantly discriminate for the outcome of MRI (p = 0.897, test
      accuracy 51%, diagnostic odds ratio 1.42). There was no correlation between the
      cumulative number of positive clinical findings in an individual patient and the
      likelihood of MRI diagnosis and no significant link between any individual
      clinical feature and the MRI result. CONCLUSIONS: Digital rectal examination has
      no significant value in the acute diagnosis of cauda equina syndrome. This study
      further confirms that there is no discreet clinical protocol applicable with
      which to confidently confirm or rule out this diagnosis. DRE is traditionally
      enshrined as an essential facet of clinical assessment in suspected cauda equina
      syndrome but it cannot be used as a discriminator to ration urgent MRI scanning.

PMID- 23113878
TI  - Long-term effectiveness and tolerability of vagal nerve stimulation in adults
      with intractable epilepsy: a retrospective analysis of 100 patients.
AB  - Data for 100 vagal nerve stimulation (VNS) patients were collected and analysed
      retrospectively. The mean seizure reduction was 17.86% (n = 67) at 6 months,
      26.21% (n = 63) at 1 year, 30.43% (n = 53) at 2 years, 48.10% (n = 40) at 3
      years, 49.44% (n = 32) at 4 years, 50.52% (n = 35) at 5 years, 45.85% (n = 31) at
      6 years, 62.68% (n = 25) at 8 years, 76.41% (n = 9) at 10 years, 82.90% (n = 4)
      at 12 years. Evidence of statistical significance for mean seizure reduction over
      time was strong with all p values less than 0.05 except at 12 years (p = 0.125)
      where the sample size was small (n = 4). Mean seizure reduction was 49.04% and 51
      (51%) patients were considered responders, defined as a 50% or more reduction in
      seizure frequency. Twenty-one (21%) patients suffered surgical complications. Of
      these 15 patients were self-limiting and 6 patients were irreversible or required
      a device revision. Fifty patients (50%) suffered from side-effects, while vagal
      stimulation cycled on (VNS on) post-operatively. However, of these, only one
      patient suffered from intolerable side effects requiring the device to be
      switched off temporarily. This study demonstrates the long-term efficacy in
      seizure reduction with the use of VNS. Complication rates and tolerability did
      not deviate greatly from that previously reported, indicating that VNS is a safe
      and effective treatment for seizure reduction in intractable epilepsy.

PMID- 23113879
TI  - Relationship of mixed bacterial infection to prognosis in foals with pneumonia
      caused by Rhodococcus equi.
AB  - BACKGROUND: Isolation of multiple bacterial species is common in foals with
      Rhodococcus equi pneumonia. HYPOTHESIS: There is no association between isolation
      of other microorganisms and outcome. ANIMALS: 155 foals with pneumonia caused by
      R. equi. METHODS: Case records of foals diagnosed with R. equi pneumonia based on
      culture of the respiratory tract were reviewed at 2 referral hospitals
      (University of Florida [UF] and Texas A&M University [TAMU]). RESULTS: R. equi
      was cultured from a tracheobronchial aspirate (TBA) in 115 foals and from lung
      tissue in 38 foals. Survival was significantly higher at UF (71%; 70/99) than at
      TAMU (50%; 28/56). R. equi was significantly more likely to grow in pure cultures
      from samples obtained from foals at UF (55%; 54/99) than from foals at TAMU (23%;
      13/56). Microorganisms cultured with R. equi included Gram-positive bacteria in
      40, Gram-negative bacteria in 41, and fungi in 23 foals. The most common bacteria
      isolated were beta-hemolytic streptococci (n = 26) and Escherichia coli (n = 18).
      Mixed infections were significantly more likely to be encountered in TBA than in
      lung tissue. Only foals from which R. equi was cultured from a TBA were included
      in the analysis for association between mixed infection and outcome. After
      adjusting for the effect of hospital using multivariate logistic regression,
      mixed culture, mixed bacterial culture, Gram-positive bacteria, beta-hemolytic
      streptococci, Gram-negative bacteria, enteric Gram-negative bacteria, nonenteric
      Gram-negative bacteria, and fungi were not significantly associated with outcome.
      CONCLUSIONS AND CLINICAL IMPORTANCE: Isolation of multiple bacteria or fungi from
      a TBA along with R. equi does not negatively impact prognosis.

PMID- 23113880
TI  - Comorbidities as a driver of the excess costs of community-acquired pneumonia in
      U.S. commercially-insured working age adults.
AB  - BACKGROUND: Adults with certain comorbid conditions have a higher risk of
      pneumonia than the overall population. If treatment of pneumonia is more costly
      in certain predictable situations, this would affect the value proposition of
      populations for pneumonia prevention. We estimate the economic impact of
      community-acquired pneumonia (CAP) for adults with asthma, diabetes, chronic
      obstructive pulmonary disease (COPD) and congestive heart failure (CHF) in a
      large U.S. commercially-insured working age population. METHODS: Data sources
      consisted of 2003 through 2007 Thomson Reuters MarketScan Commercial Claims and
      Encounters and Thomson Reuters Health Productivity and Management (HPM)
      databases. Pneumonia episodes and selected comorbidities were identified by ICD-9
      CM diagnosis codes. By propensity score matching, controls were identified for
      pneumonia patients. Excess direct medical costs and excess productivity cost were
      estimated by generalized linear models (GLM). RESULTS: We identified 402,831
      patients with CAP between 2003 through 2007, with 25,560, 32,677, 16,343, and
      5,062 episodes occurring in patients with asthma, diabetes, COPD and CHF,
      respectively. Mean excess costs (and standard error, SE) of CAP were $14,429
      (SE=44) overall. Mean excess costs by comorbidity subgroup were lowest for asthma
      ($13,307 (SE=123)), followed by diabetes ($21,395 (SE=171)) and COPD ($23,493
      (SE=197)); mean excess costs were highest for patients with CHF ($34,436
      (SE=549)). On average, indirect costs comprised 21% of total excess costs,
      ranging from 8% for CHF patients to 27% for COPD patients. CONCLUSIONS: Compared
      to patients without asthma, diabetes, COPD, or CHF, the excess cost of CAP is
      nearly twice as high for patients with diabetes and COPD and nearly three times
      as high for patients with CHF. Indirect costs made up a significant but varying
      portion of excess CAP costs. Returns on prevention of pneumonia would therefore
      be higher in adults with these comorbidities.

PMID- 23113881
TI  - Human papilloma virus vaccination programs reduce health inequity in most
      scenarios: a simulation study.
AB  - BACKGROUND: The global and within-country epidemiology of cervical cancer
      exemplifies health inequity. Public health programs may reduce absolute risk but
      increase inequity; inequity may be further compounded by screening programs. In
      this context, we aimed to explore what the impact of human papillomavirus (HPV)
      vaccine might have on health equity allowing for uncertainty surrounding the long
      term effect of HPV vaccination programs. METHODS: A simple static multi-way
      sensitivity analysis was carried out to compare the relative risk, comparing
      after to before implementation of a vaccination program, of infections which
      would cause invasive cervical cancer if neither prevented nor detected, using
      plausible ranges of vaccine effectiveness, vaccination coverage, screening
      sensitivity, screening uptake and changes in uptake. RESULTS: We considered a
      total number of 3,793,902 scenarios. In 63.9% of scenarios considered,
      vaccination would lead to a better outcome for a population or subgroup with that
      combination of parameters. Regardless of vaccine effectiveness and coverage, most
      simulations led to lower rates of disease. CONCLUSIONS: If vaccination coverage
      and screening uptake are high, then communities are always better off with a
      vaccination program. The findings highlight the importance of achieving and
      maintaining high immunization coverage and screening uptake in high risk groups
      in the interest of health equity.

PMID- 23113882
TI  - Association of adipokines and adhesion molecules with indicators of obesity in
      women undergoing mammography screening.
AB  - BACKGROUND: The soluble cell adhesion molecules and adipokines are elevated in
      patients with obesity, hypertension, type 2 diabetes mellitus, breast cancer and
      atherosclerosis. OBJECTIVE: To investigate the relationship between
      anthropometric profile, dietary intake, lipid profile and fasting glycemia with
      serum levels of adipokines (adiponectin and PAI-1) and adhesion molecules (ICAM-1
      and VCAM-1) in women without breast cancer undergoing routine mammographic
      screening. DESIGN: Transversal study. SUBJECTS: One hundred and forty-five women
      over 40-years old participated in this study. RESULTS: In 39.3% of cases the BMI
      was above 30 kg/m2; 46.9% had hypertension, 14.5% had type 2 Diabetes Mellitus,
      31.7% had dyslipidemia and 88.3% presented a waist-to-hip ratio >= 0.8. A linear
      correlation was found between serum levels of PAI-1 and triglycerides, between
      serum levels of PAI-1 and WHR and between serum levels of VCAM-1 and BMI.
      CONCLUSION: We found a high prevalence of obesity and metabolic syndrome. PAI-1
      and VCAM-1 levels were correlated with clinical indicators of obesity and
      overweight.

PMID- 23113883
TI  - Estrous cycle-dependent changes of Fas expression in the bovine corpus luteum:
      influence of keratin 8/18 intermediate filaments and cytokines.
AB  - BACKGROUND: Fas expression and Fas-induced apoptosis are mechanisms attributed to
      the selective destruction of cells of the corpus luteum (CL) during luteal
      regression. In certain cell-types, sensitivity to these death-inducing mechanisms
      is due to the loss or cleavage of keratin-containing intermediate filaments.
      Specifically, keratin 8/18 (K8/K18) filaments are hypothesized to influence cell
      death in part by regulating Fas expression at the cell surface. METHODS: Here,
      Fas expression on bovine luteal cells was quantified by flow cytometry during the
      early (Day 5, postovulation) and late stages (Days 16-18, postovulation) of CL
      function, and the relationship between Fas expression, K8/K18 filament expression
      and cytokine-induced cell death in vitro was evaluated. RESULTS: Both total and
      cell surface expression of Fas on luteal cells was greater for early versus late
      stage bovine CL (89% vs. 44% of cells for total Fas; 65% vs.18% of cells for cell
      surface Fas; respectively, P<0.05, n=6-9 CL/stage). A similar increase in the
      steady-state concentration of mRNA for Fas, as detected by quantitative real-time
      polymerase chain reaction, however, was not observed. Transient disruption of
      K8/K18 filaments in the luteal cells with acrylamide (5 mM), however, had no
      effect on the surface expression of Fas (P>0.05, n=4 CL/stage), despite evidence
      these conditions increased Fas expression on HepG2 cells (P<0.05, n= 3 expts).
      Exposure of the luteal cells to cytokines induced cell death (P<0.05) as
      expected, but there was no effect of K8/K18 filament disruption by acrylamide
      (P>0.05) or stage of CL (P>0.05, n= 4 CL/stage) on this outcome. CONCLUSION: In
      conclusion, we rejected our null hypothesis that the cell surface expression of
      Fas does not differ between luteal cells of early and late stage CL. The results
      also did not support the idea that K8/K18 filaments influence the expression of
      Fas on the surface of bovine luteal cells. Potential downstream effects of these
      filaments on death signaling, however, remain a possibility. Importantly, the
      elevated expression of Fas observed on cells of early stage bovine CL compared to
      late stage bovine CL raises a provocative question concerning the physiological
      role(s) of Fas in the corpus luteum, particularly during early luteal
      development.

PMID- 23113885
TI  - The quality of the bone marrow sample for successful conventional cytogenetic
      analysis is important.

PMID- 23113884
TI  - Diversity of heterotrimeric G-protein gamma subunits in plants.
AB  - BACKGROUND: Heterotrimeric G-proteins, consisting of three subunits Galpha, Gbeta
      and Ggamma are present in most eukaryotes and mediate signaling in numerous
      biological processes. In plants, Ggamma subunits were shown to provide functional
      selectivity to G-proteins. Three unconventional Ggamma subunits were recently
      reported in Arabidopsis, rice and soybean but no structural analysis has been
      reported so far. Their relationship with conventional Ggamma subunits and
      taxonomical distribution has not been yet demonstrated. RESULTS: After an
      extensive similarity search through plant genomes, transcriptomes and proteomes
      we assembled over 200 non-redundant proteins related to the known Ggamma
      subunits. Structural analysis of these sequences revealed that most of them lack
      the obligatory C-terminal prenylation motif (CaaX). According to their C-terminal
      structures we classified the plant Ggamma subunits into three distinct types.
      Type A consists of Ggamma subunits with a putative prenylation motif. Type B
      subunits lack a prenylation motif and do not have any cysteine residues in the C
      terminal region, while type C subunits contain an extended C-terminal domain
      highly enriched with cysteines. Comparative analysis of C-terminal domains of the
      proteins, intron-exon arrangement of the corresponding genes and phylogenetic
      studies suggested a common origin of all plant Ggamma subunits. CONCLUSION:
      Phylogenetic analyses suggest that types C and B most probably originated
      independently from type A ancestors. We speculate on a potential mechanism used
      by those Ggamma subunits lacking isoprenylation motifs to anchor the Gbetagamma
      dimer to the plasma membrane and propose a new flexible nomenclature for plant
      Ggamma subunits. Finally, in the light of our new classification, we give a word
      of caution about the interpretation of Ggamma research in Arabidopsis and its
      generalization to other plant species.

PMID- 23113886
TI  - Unilateral eyelid involvement in discoid lupus erythematosus.

PMID- 23113887
TI  - Omega-3 fatty acids deficiency aggravates glutamatergic synapse and astroglial
      aging in the rat hippocampal CA1.
AB  - Epidemiological data suggest that a poor omega3 status favoured by the low
      omega3/omega6 polyunsaturated fatty acids ratio in western diets contributes to
      cognitive decline in the elderly, but mechanistic evidence is lacking. We
      therefore explored the impact of omega3 deficiency on the evolution of
      glutamatergic transmission in the CA1 of the hippocampus during aging by
      comparing 4 groups of rats aged 6-22 months fed omega3-deficient or omega3/omega6
      balanced diets from conception to sacrifice: Young omega3 Balanced (YB) or
      Deficient (YD), Old omega3 Balanced (OB) or Deficient (OD) rats. omega3
      Deficiency induced a 65% decrease in the amount of docosahexaenoic acid (DHA, the
      main omega3 in cell membranes) in brain phospholipids, but had no impact on
      glutamatergic transmission and astroglial function in young rats. Aging induced a
      10% decrease in brain DHA, a 35% reduction of synaptic efficacy (fEPSP/PFV) due
      to decreased presynaptic glutamate release and a 30% decrease in the astroglial
      glutamate uptake associated with a marked astrogliosis (+100% GFAP). The omega3
      deficiency further decreased these hallmarks of aging (OD vs. OB rats: -35%
      fEPSP/PFV P < 0.05, -15% astroglial glutamate uptake P < 0.001, +30% GFAP P <
      0.01). This cannot be attributed to aggravation of the brain DHA deficit because
      the brains of OD rats had more DHA than those of YD rats. Thus, omega3 deficiency
      worsens the age-induced degradation of glutamatergic transmission and its
      associated astroglial regulation in the hippocampus.

PMID- 23113888
TI  - Who's driving anyway? Herculean efforts to identify the drivers of breast cancer.
AB  - The continuing advancement of sequencing technologies has made the systematic
      identification of all driving somatic events in cancer a possibility. In the June
      2012 issue of Nature, five papers show some significant headway in this endeavor,
      each a herculean effort of genome sequencing, and transcriptome and copy number
      analysis resulting in data on thousands of breast cancers. Integrating these
      massive datasets, the authors were able to further subdivide breast cancer and
      identify a number of novel driver genes. While the studies represent a leap
      forward in describing the genomics of breast cancer, and clearly highlight the
      tremendous diversity between tumors, the studies only scrape the surface of
      molecular changes in breast tumors, with more granularity to come from the study
      of epigenomics, single cell sequencing, and so on. The immediate importance of
      the data to clinical care is currently unknown, and will depend upon detailed
      identification and functional analysis of driver mutations. 

PMID- 23113889
TI  - Molecular cloning of IGlambda rearrangements using long-distance inverse PCR (LDI
      PCR).
AB  - OBJECTIVES: Malignant cells of mature B-cell origin show tumor-specific clonal
      immunoglobulin gene (IG) rearrangements, including V(D)J recombinations,
      nucleotide mutations, or translocations. Rapid molecular cloning of the
      breakpoint sequence by long-distance inverse PCR (LDI-PCR) has so far been
      applied to rearrangements targeted to IGH joining, IGH switch, and IGkappa
      regions. We tended to apply LDI-PCR method for cloning of IGlambda
      rearrangements. METHODS: To identify which IGlambda isotype segment was
      rearranged, we performed Southern blot analysis using isotype-specific probes. We
      set inverse primers on the telomeric side of each joining region and amplified
      rearranged bands detected by Southern blot analysis as corresponding PCR
      products. RESULTS: All germline IGlambda segments were successfully amplified as
      expected PCR products. We determined breakpoint sequences of five chromosome
      translocations involving IGlambda locus: three novel t(8;22)(q24;q11), one known
      t(3;22)(q27;q11), and one partially known t(11;22)(q13;q11). Two of the three
      t(8;22)(q24;q11) were involved in Jlambda with a recombination signal sequence
      and one of three in the first exon of IGLL5, which lies upstream of Jlambda1.
      Three 8q24 breakpoints were widespread at 132, 260 and 366 kb downstream of MYC
      locus. The t(3;22)(q27;q11) showed a juxtaposition of Jlambda2 and the first
      intron of BCL6, as previously reported. In t(11;22)(q13;q11), 3'UTR of cyclin D1
      fused to the constant region of lambda7 with nucleotide mutations. We also
      amplified four Vlambda/Jlambda recombination sequences. CONCLUSION: Our method is
      a useful tool for molecular analysis of genetic events in IGlambda.

PMID- 23113891
TI  - Resistance to Care: contributing factors and associated behaviours in healthcare
      facilities.
AB  - AIMS: This article reports results of a study of contributing factors and
      associated behaviours in specific clinical areas to resistance to care episodes.
      BACKGROUND: Resistance to Care has previously been studied in aged care settings,
      and previous studies have reported patient behaviours and appropriate responses.
      Resistance to Care is a defensive response by patients towards healthcare staff
      and is demonstrated in various non-compliant behaviours. DESIGN: Cross-sectional
      study. METHODS: A cross-sectional survey of a representative sample of nurses (n
      = 5044), who were members of the New South Wales Nurses' Association in
      Australia, was conducted in 2008-2009. RESULTS: Resistance to Care episodes occur
      in various clinical settings and may be precipitated by a range of clinical
      diagnoses and symptoms. They may also be triggered during various nursing
      activities that nurses recognize as high-risk for these episodes. CONCLUSION: The
      reported Resistance to Care behaviours are similar to those reported in studies
      of aggression and violence; however, they require a substantially different
      response by nurses in various clinical contexts.

PMID- 23113892
TI  - The acceptability to Aboriginal Australians of a family-based intervention to
      reduce alcohol-related harms.
AB  - INTRODUCTION AND AIMS: Cognitive-behavioural interventions that use familial and
      community reinforcers in an individual's environment are effective for reducing
      alcohol-related harms. Such interventions have considerable potential to reduce
      the disproportionately high burden of alcohol-related harm among Aboriginal
      Australians if they can be successfully tailored to their specific needs and
      circumstances. The overall aim of this paper is to describe the perceived
      acceptability of two cognitive-behavioural interventions, the Community
      Reinforcement Approach (CRA) and Community Reinforcement and Family Training
      (CRAFT), to a sample of Aboriginal people. DESIGN AND METHODS: Descriptive survey
      was administered to 116 Aboriginal people recruited through an Aboriginal
      Community Controlled Health Service and a community-based drug and alcohol
      treatment agency in rural New South Wales, Australia. RESULTS: Participants
      perceived CRA and CRAFT to be highly acceptable for delivery in their local
      Aboriginal community. Women were more likely than men to perceive CRAFT as highly
      acceptable. Participants expressed a preference for counsellors to be someone
      they knew and trusted, and who has experience working in their local community.
      CRA was deemed most acceptable for delivery to individuals after alcohol
      withdrawal and CRAFT for people who want to help a relative/friend start alcohol
      treatment. There was a preference for five or more detailed sessions. DISCUSSION
      AND CONCLUSIONS: Findings of this study suggest that CRA and CRAFT are likely to
      be acceptable for delivery to some rural Aboriginal Australians, and that there
      is potential to tailor these interventions to specific communities.

PMID- 23113893
TI  - SAP155-mediated c-myc suppressor far-upstream element-binding protein-interacting
      repressor splicing variants are activated in colon cancer tissues.
AB  - The c-myc transcriptional suppressor, far-upstream element (FUSE)-binding protein
      (FBP)-interacting repressor (FIR), is alternatively spliced in colorectal cancer
      tissue (Matsushita et al., Cancer Res 2006). Recently, the knockdown of SAP155
      pre-mRNA-splicing factor, a subunit of SF3b, was reported to disturb FIR pre-mRNA
      splicing and yield FIRDeltaexon2, an exon 2-spliced variant of FIR, which lacks c
      myc repression activity. In the present study, novel splicing variants of FIR,
      Delta3 and Delta4, were also generated by SAP155 siRNA, and these variants were
      found to be activated in human colorectal cancer tissue. Furthermore, the
      expression levels of FIR variant mRNA were examined in the peripheral blood of
      colorectal cancer patients and healthy volunteers to assess its potency for tumor
      detection. As expected, circulating FIR variant mRNA in the peripheral blood of
      cancer patients were significantly overexpressed compared to that in healthy
      volunteers. In particular, the area under the receiving operating characteristic
      curve of FIR, FIRDeltaexon2 or FIRDeltaexon2/FIR, was greater than those of
      conventional carcinoembryonic antigen or carbohydrate antigen 19-9. In addition,
      FIRDeltaexon2 or FIR mRNA expression in the peripheral blood was significantly
      reduced after operative removal of colorectal tumors. Thus, circulating FIR and
      FIRDeltaexon2 mRNA are potential novel screening markers for colorectal cancer
      testing with conventional carcinoembryonic antigen and or carbohydrate antigen 19
      9. Taken together, our results indicate that overexpression of FIR and its
      splicing variants in colorectal cancer directs feed-forward or addicted circuit c
      myc transcriptional activation. Clinical implications for colorectal cancers of
      novel FIR splicing variants are also discussed in the present paper.

PMID- 23113894
TI  - Endotoxemia after high cutoff hemodialysis for treatment of patient with multiple
      myeloma can be prevented by using ultrapure dialysate: a case report.
AB  - To report endotoxemia presented in a case with multiple myeloma (MM) treated by
      high cutoff hemodialysis (HCO-HD) being prevented by using ultrapure dialysate. A
      female inpatient with MM received six times HCO-HD (HCO 2100 dialyzer) within 3
      weeks after initiation of a chemotherapy based on
      vincristine+epirubicin+dexamethasone protocol. Conventional dialysate was used in
      the first three times and then changed to ultrapure dialysate due to elevation of
      body temperature after HCO-HD. Free light chains (FLC) and endotoxin levels in
      blood and dialysate were monitored. After six times HCO-HD, her serum FLC lambda
      decreased from 4689 mg/L to 492.7 mg/L, with a trend of decline of serum
      creatinine. The clearance, reduction ratio, and removal amount of FLC lambda was
      38.4 mL/min, 71.0-85.2%, and 9.06-18.02 g, respectively, in the setting of
      dialysate flow rate 500 mL/min, while in the setting of dialysate flow rate 200
      mL/min, the removal efficacy of FLC lambda was lower than the former. A rise of
      body temperature up to 38.5 degrees C after treatment and endotoxemia (endotoxin
      levels 0.122 EU/mL) was found when using conventional dialysate (endotoxin levels
      0.112-0.145 EU/mL), but not seen after changing to ultrapure dialysate. Combined
      with appropriate chemotherapy, HCO-HD can effectively remove and reduce blood
      FLC. Attention should be paid to the endotoxemia and the rise of temperature
      after treatment when conventional dialysate is used, which can be prevented by
      using ultrapure dialysate.

PMID- 23113895
TI  - Lower nutritional status and higher food insufficiency in frail older US adults.
AB  - Frailty is a state of decreased physical functioning and a significant
      complication of ageing. We examined frailty, energy and macronutrient intake,
      biomarkers of nutritional status and food insufficiency in US older adult (age >=
      60 years) participants of the Third National Health and Nutrition Examination
      Survey (n 4731). Frailty was defined as meeting >= 2 and pre-frailty as meeting
      one of the following four-item criteria: (1) slow walking; (2) muscular weakness;
      (3) exhaustion and (4) low physical activity. Intake was assessed by 24 h dietary
      recall. Food insufficiency was self-reported as 'sometimes' or 'often' not having
      enough food to eat. Analyses were adjusted for sex, race, age, smoking,
      education, income, BMI, other co-morbid conditions and complex survey design.
      Prevalence of frailty was highest among people who were obese (20.8 %), followed
      by overweight (18.4 %), normal weight (16.1 %) and lowest among people who were
      underweight (13.8 %). Independent of BMI, daily energy intake was lowest in
      people who were frail, followed by pre-frail and highest in people who were not
      frail (6648 (se 130), 6966 (se 79) and 7280 (se 84) kJ, respectively, P< 0.01).
      Energy-adjusted macronutrient intakes were similar in people with and without
      frailty. Frail (adjusted OR (AOR) 4.7; 95 % CI 1.7, 12.7) and pre-frail (AOR 2.1;
      95 % CI 0.8, 5.8) people were more likely to report being food insufficient than
      not frail people. Serum albumin, carotenoids and Se levels were lower in frail
      adults than not frail adults. Research is needed on targeted interventions to
      improve nutritional status and food insufficiency among frail older adults, while
      not necessarily increasing BMI.

PMID- 23113896
TI  - Is there an association between thrombosis and fibroids? A single centre
      experience and literature review.

PMID- 23113897
TI  - Clostridium difficile 027-associated pseudomembranous colitis after short-term
      treatment with cefuroxime and cephalexin in an elderly orthopedic patient: a case
      report.
AB  - BACKGROUND: Clostridium difficile ribotype 027 has become increasingly prevalent
      in European countries. The clinical picture varies from self-limiting diarrhea to
      pseudomembranous colitis with toxic megacolon and ultimately death. Use of
      antibiotics is the principal risk factor; others include comorbidity, advanced
      age and hospitalization. However even with extensive knowledge of risk factors,
      it remains difficult to define "minimum risk," as illustrated by the following
      case. CASE PRESENTATION: An 80-year-old Danish man in good health was
      hospitalized for a penetrating knee injury. He received 5 days of intravenous
      cefuroxime after surgical revision and was discharged with oral cephalexin. Post
      discharge he suffered from abdominal discomfort and was readmitted with ileus 4
      days after discharge, i.e. 10 days after initiation of antibiotic treatment. His
      condition deteriorated, and pseudomembranous colitis was diagnosed. Due to lack
      of response to vancomycin and metronidazole, a total colectomy was performed.
      Stool cultures were positive for CD 027. CONCLUSION: Short-term use of
      cephalosporins may have induced CD 027 infection, and the patient's age was the
      only identifiable risk factor for the fulminant course. Thus, even short-term
      prophylactic treatment with cephalosporins cannot be considered entirely safe.

PMID- 23113898
TI  - Effects of multicomponent exercise on cognitive function in older adults with
      amnestic mild cognitive impairment: a randomized controlled trial.
AB  - BACKGROUND: To examine the effects of a multicomponent exercise program on the
      cognitive function of older adults with amnestic mild cognitive impairment
      (aMCI). METHODS:  DESIGN: Twelve months, randomized controlled trial; SETTING:
      Community center in Japan; PARTICIPANTS: Fifty older adults (27 men) with aMCI
      ranging in age from 65 to 93 years (mean age, 75 years); INTERVENTION: Subjects
      were randomized into either a multicomponent exercise (n = 25) or an education
      control group (n = 25). Subjects in the multicomponent exercise group exercised
      under the supervision of physiotherapists for 90 min/d, 2 d/wk, for a total of 80
      times over 12 months. The exercises included aerobic exercises, muscle strength
      training, and postural balance retraining, and were conducted using multiple
      conditions to stimulate cognitive functions. Subjects in the control group
      attended three education classes regarding health during the 12-month period.
      MEASUREMENTS were administered before, after the 6-month, and after the 12-month
      intervention period; MEASUREMENTS: The performance measures included the mini
      mental state examination, logical memory subtest of the Wechsler memory scale
      revised, digit symbol coding test, letter and categorical verbal fluency test,
      and the Stroop color word test. RESULTS: The mean adherence to the exercise
      program was 79.2%. Improvements of cognitive function following multicomponent
      exercise were superior at treatment end (group * time interactions for the mini
      mental state examination (P = 0.04), logical memory of immediate recall (P =
      0.03), and letter verbal fluency test (P = 0.02)). The logical memory of delayed
      recall, digit symbol coding, and Stroop color word test showed main effects of
      time, although there were no group * time interactions. CONCLUSIONS: This study
      indicates that exercise improves or supports, at least partly, cognitive
      performance in older adults with aMCI.

PMID- 23113899
TI  - Was there a disparity in age appropriate infant immunization uptake in the
      theatre of war in the North of Sri Lanka at the height of the hostilities?: a
      cross-sectional study in resettled areas in the Kilinochchi district.
AB  - BACKGROUND: It was long speculated that there could be under-immunized pockets
      in the war affected Northern part of Sri Lanka relative to other areas. With the
      cessation of hostilities following the military suppression of the rebellion,
      opportunities have arisen to appraise the immunization status of children in
      areas of re-settlement in former war ravaged districts. METHODS: We conducted a
      cross-sectional study to describe the coverage and age appropriateness of infant
      vaccinations in a former conflict district during the phase of re-settlement. The
      target population comprised all children of re-settled families in the age group
      of 12 - 23 months in the district. We selected a study sample of 300 children
      from among the target population using the WHO's 30 cluster EPI survey method.
      Trained surveyors collected data using a structured checklist. The infant
      vaccination status was ascertained by reviewing vaccination records in the Child
      Health Development Record or any other alternative documentary evidence. RESULTS:
      The survey revealed that the proportion of fully vaccinated children in the
      district was 91%. For individual vaccines, it ranged from 92% (measles) to 100%
      (BCG, DPT/OPV1). However, the age appropriateness of vaccination was less than
      50% for all antigens except for BCG (94%). The maximum number of days of delay of
      vaccinations ranged from 21 days for BCG to 253 days for measles. Age appropriate
      vaccination rates significantly differed for DPT/OPV1-3 and measles during the
      conflict and post-conflict stages while it did not for the BCG. Age appropriate
      vaccination rates were significantly higher for DPT/OPV1-3 during the conflict
      while for the measles it was higher in the post conflict stage. CONCLUSIONS:
      Though the vaccination coverage for infant vaccines in the war affected
      Kilinochchi district was similar to other districts in the country, it masked a
      disparity in terms of low age-appropriateness of infant immunizations given in
      field settings. This finding underscores the need for investigation of underlying
      reasons and introduction of remedial measures in the stage of restoring Primary
      Health Care services in the ex-conflict zone.

PMID- 23113901
TI  - Patterns of neuropsychiatric sub-syndromes in Brazilian and Norwegian patients
      with dementia.
AB  - BACKGROUND: Neuropsychiatric symptoms (NPS) affect the majority of patients who
      have dementia. Neuropsychiatric sub-syndromes with symptoms that occur together
      and have common neurobiological correlates have been identified. There are scarce
      data regarding the comparison of the pattern of the neuropsychiatric sub
      syndromes in distinct ethnical and cultural populations. We aim at comparing the
      pattern of the NPS, and the factor analysis of the Neuropsychiatric Inventory
      (NPI-10) in two samples of outpatients with dementia living in Brazil and Norway.
      METHODS: This is a cross-sectional study. The sample consists of 168 Brazilian
      and 155 Norwegian demented patients from psychogeriatric facilities and community
      based educational programs. Brazilian patients were diagnosed with Alzheimer's
      disease (63.7%), vascular dementia (15.5%), or mixed dementia (20.8%), whereas
      the diagnoses of Norwegian patients were Alzheimer's disease (97.4%) and mixed
      dementia (2.6%). Principal component analysis with the Varimax rotation was used
      for factor analysis of the NPI-10. RESULTS: Apathy (80.4 %), agitation/aggression
      (45.8%), and aberrant motor behavior (45.8%) were the most common symptoms in the
      Brazilian sample. Apathy (72.3%), dysphoria (61.9%), and anxiety (52.3%) were the
      most frequent symptoms in the Norwegian sample. Factor analysis of the NPI-10
      revealed three syndromes for the Brazilian (Psychosis, Mood, Psychomotor) and
      Norwegian (Psychosis, Mood, Frontal) groups. CONCLUSIONS: The frequency of
      individual NPS may differ among distinct populations. However, Psychosis and
      Depression are common sub-syndromes in diverse ethnical and cultural patients
      with dementia. Our findings support the syndromic approach for the clinical
      assessment of the patients with dementia.

PMID- 23113902
TI  - Linear IgA bullous dermatosis following human papillomavirus vaccination.

PMID- 23113900
TI  - Selective gene-expression profiling of migratory tumor cells in vivo predicts
      clinical outcome in breast cancer patients.
AB  - INTRODUCTION: Metastasis of breast cancer is the main cause of death in patients.
      Previous genome-wide studies have identified gene-expression patterns correlated
      with cancer patient outcome. However, these were derived mostly from whole tissue
      without respect to cell heterogeneity. In reality, only a small subpopulation of
      invasive cells inside the primary tumor is responsible for escaping and
      initiating dissemination and metastasis. When whole tissue is used for molecular
      profiling, the expression pattern of these cells is masked by the majority of the
      noninvasive tumor cells. Therefore, little information is available about the
      crucial early steps of the metastatic cascade: migration, invasion, and entry of
      tumor cells into the systemic circulation. METHODS: In the past, we developed an
      in vivo invasion assay that can capture specifically the highly motile tumor
      cells in the act of migrating inside living tumors. Here, we used this assay in
      orthotopic xenografts of human MDA-MB-231 breast cancer cells to isolate
      selectively the migratory cell subpopulation of the primary tumor for gene
      expression profiling. In this way, we derived a gene signature specific to breast
      cancer migration and invasion, which we call the Human Invasion Signature (HIS).
      RESULTS: Unsupervised analysis of the HIS shows that the most significant
      upregulated gene networks in the migratory breast tumor cells include genes
      regulating embryonic and tissue development, cellular movement, and DNA
      replication and repair. We confirmed that genes involved in these functions are
      upregulated in the migratory tumor cells with independent biological repeats. We
      also demonstrate that specific genes are functionally required for in vivo
      invasion and hematogenous dissemination in MDA-MB-231, as well as in patient
      derived breast tumors. Finally, we used statistical analysis to show that the
      signature can significantly predict risk of breast cancer metastasis in large
      patient cohorts, independent of well-established prognostic parameters.
      CONCLUSIONS: Our data provide novel insights into, and reveal previously unknown
      mediators of, the metastatic steps of invasion and dissemination in human breast
      tumors in vivo. Because migration and invasion are the early steps of metastatic
      progression, the novel markers that we identified here might become valuable
      prognostic tools or therapeutic targets in breast cancer.

PMID- 23113904
TI  - The addition of pyloroplasty as a new surgical approach to enhance effectiveness
      of gastric electrical stimulation therapy in patients with gastroparesis.
AB  - BACKGROUND: Improvement of gastroparesis (GP) symptoms has been documented in
      patients treated with gastric electrical stimulation (GES), but acceleration of
      gastric emptying (GET) is unpredictable. The aim of our study was to evaluate the
      advantage of adding surgical pyloroplasty (PP) to GES for improvement of GET and
      control of symptoms in diabetes mellitus (DM), idiopathic (ID), and postvagotomy
      (P-V) GP. METHODS: A total of 49 (17 - DM, 9 - ID, 23 - P-V) consecutive GP
      patients: 38 female; mean age 42 (21-73 years); mean weight 158 lbs (102-245),
      underwent GES implantation, and 26 (53%) additionally received PP. Total Symptoms
      Score, 4-h GET, adverse events (AEs), and days of hospitalizations were captured
      at baseline and at the last visit. KEY RESULTS: The mean follow-up was 7 months.
      Total Symptoms Score in patients who received Enterra and PP or GES alone
      significantly improved compared to their baseline scores (P < 0.001). GET
      improved by 64% at 4 h (P < 0.001) in patients with Enterra and PP, compared to
      7% observed after GES therapy alone (ns). The most impressive acceleration of GET
      was seen in the P-V group, who received both therapies (P = 0.004) and 8 (60%) of
      them normalized GET. No AEs accompanied the addition of PP to the Enterra
      surgery. CONCLUSIONS & INFERENCES: (i) In drug-refractory GP the addition of PP
      to GES substantially accelerated GET; (ii) The GET response in P-V group was the
      most impressive; (iii) Significant symptom reductions were achieved by both
      procedures; and (iv) PP added to GES may sustain better long-term symptoms
      control particularly in the P-V setting.

PMID- 23113903
TI  - Macropinocytosis is responsible for the uptake of pathogenic and non-pathogenic
      mycobacteria by B lymphocytes (Raji cells).
AB  - BACKGROUND: The classical roles of B cells include the production of antibodies
      and cytokines and the generation of immunological memory, these being key factors
      in the adaptive immune response. However, their role in innate immunity is
      currently being recognised. Traditionally, B cells have been considered non
      phagocytic cells; therefore, the uptake of bacteria by B cells is not extensively
      documented. In this study, we analysed some of the features of non-specific
      bacterial uptake by B lymphocytes from the Raji cell line. In our model, B cells
      were infected with Mycobacterium tuberculosis (MTB), Mycobacterium smegmatis
      (MSM), and Salmonella typhimurium (ST). RESULTS: Our observations revealed that
      the Raji B cells were readily infected by the three bacteria that were studied.
      All of the infections induced changes in the cellular membrane during bacterial
      internalisation. M. smegmatis and S. typhimurium were able to induce important
      membrane changes that were characterised by abundant filopodia and lamellipodia
      formation. These membrane changes were driven by actin cytoskeletal
      rearrangements. The intracellular growth of these bacteria was also controlled by
      B cells. M. tuberculosis infection also induced actin rearrangement-driven
      membrane changes; however, the B cells were not able to control this infection.
      The phorbol 12-myristate 13-acetate (PMA) treatment of B cells induced filopodia
      and lamellipodia formation, the production of spacious vacuoles (macropinosomes),
      and the fluid-phase uptake that is characteristic of macropinocytosis. S.
      typhimurium infection induced the highest fluid-phase uptake, although both
      mycobacteria also induced fluid uptake. A macropinocytosis inhibitor such as
      amiloride was used and abolished the bacterial uptake and the fluid-phase uptake
      that is triggered during the bacterial infection. CONCLUSIONS: Raji B cells can
      internalise S. typhimurium and mycobacteria through an active process, such as
      macropinocytosis, although the resolution of the infection depends on factors
      that are inherent in the virulence of each pathogen.

PMID- 23113906
TI  - A new type of molybdenum oxide crystal encapsulated inside a single-walled carbon
      nanotube.
AB  - The crystal structure of a new type of molybdenum oxide crystal encapsulated in a
      single-walled carbon nanotube (CNT) was examined via diffraction and
      spectroscopic techniques using both X-rays and electron beams. This new type of
      molybdenum oxide crystal has a chemical bonding state of MoO3, as confirmed by X
      ray absorption spectroscopy, and the MoO3 units exhibit axial symmetry, as
      clarified by electron diffraction from bundled and individual CNTs encapsulating
      the crystal. To obtain three-dimensional information on the structure, a cross
      sectional sample was prepared using a conventional dimple and ion-mill method.
      High-resolution transmission electron microscopy images exhibit ring-like shapes
      that originated from the arrangement of the MoO3 units inside the CNTs, as
      observed along the tube axis. The units are spaced 0.36 nm from each other in a
      ring arrangement and the distance between each ring is 0.391 nm.

PMID- 23113905
TI  - Twenty-five year trends in body mass index by education and income in Finland.
AB  - BACKGROUND: The socioeconomic gradient in obesity and overweight is amply
      documented. However, the contribution of different socioeconomic indicators on
      trends of body mass index (BMI) over time is less well known. The aim of this
      study was to investigate the associations of education and income with (BMI) from
      the late 1970s to the early 2000s. METHODS: Data were derived from nationwide
      cross-sectional health behaviour surveys carried out among Finns annually since
      1978. This study comprises data from a 25-year period (1978-2002) that included
      25 339 men and 25 330 women aged 25-64 years. BMI was based on self-reported
      weight and height. Education in years was obtained from the questionnaire and
      household income from the national tax register. In order to improve the
      comparability of the socioeconomic position measures, education and income were
      divided into gender-specific tertiles separately for each study year. Linear
      regression analysis was applied. RESULTS: An increase in BMI was observed among
      men and women in all educational and income groups. In women, education and
      income were inversely associated with BMI. The magnitudes of the associations
      fluctuated but stayed statistically significant over time. Among the Finnish men,
      socioeconomic differences were more complicated. Educational differences were
      weaker than among the women and income differences varied according to
      educational level. At the turn of the century, the high income men in the lowest
      educational group had the highest BMI whereas the income pattern in the highest
      educational group was the opposite. CONCLUSION: No overall change in the socio
      economic differences of BMI was observed in Finland between 1978 and 2002.
      However, the trends of BMI diverged in sub-groups of the studied population: the
      most prominent increase in BMI took place in high income men with low education
      and in low income men with high education. The results encourage further research
      on the pathways between income, education, living conditions and the increasing
      BMI.

PMID- 23113907
TI  - Interprofessional education: a vital concern and a lever to better primary care.

PMID- 23113908
TI  - Tackling avoidable hospital admissions: improving or compromising quality?

PMID- 23113909
TI  - Speaking of risk, managing uncertainty: decision-making about cholesterol
      reducing treatment in general practice.
AB  - BACKGROUND: Decision making regarding treatment options and risk communication
      between health professionals and patients have become key areas of research and
      quality improvement. Decisions are directed towards applying evidence, exploring
      individual patient concerns, and addressing  medical uncertainty. Compared with
      research on health professionals' views on higher stakes decisions, relatively
      little attention has been paid to improving decision making and risk
      communication for lifestyle-related risk conditions involving lower stakes or
      longer term treatment options,  such as medication to reduce risk of future
      disease. AIM: To examine general practitioners (GPs) who experienced difficulties
      with decision making regarding treatment options and risk communication with
      asymptomatic patients with high cholesterol and risk of cardiovascular disease.
      METHODS: An exploratory qualitative and ethnographically informed approach was
      used. Danish GPs (six male, six female, average age 48 years), were interviewed
      in three groups. Interviews were transcribed and coded, while analytical concepts
      about medical uncertainty were identified. RESULTS: The study identified two
      modalities of medical uncertainty: epistemological uncertainty about scientific
      knowledge and evidence-based medicine; and situational uncertainty produced in
      the one-to-one relationship between the GP and the patient during the
      consultation. The study also stressed  that the decision making about cholesterol
      reducing treatment is interpreted by the GPs as reversible and provisional.
      CONCLUSION: These modalities of medical uncertainty can be addressed proactively
      when developing concepts, tools and training interventions to optimise
      communication  about treatment options in primary care.

PMID- 23113910
TI  - Stakeholders' perspectives on quality indicators for diabetes care: a qualitative
      study.
AB  - BACKGROUND: Transparency in diabetes care requires quality indicators that are of
      interest to stakeholders in order to optimise their usage. Indicator development
      is often focused on consensus, and little is known about stakeholders'
      preferences for information on quality. AIM: To explore the preferences of
      consumers, providers, purchasers and policy makers for different quality domains
      and indicators in relation to the intended use of quality indicators. METHODS:
      Between June and December 2009, 14 semi-structured interviews were held with
      stakeholders  who have a decisive vote in the selection of the national indicator
      set for diabetes care in the Netherlands. The following subjects were explored:
      (1) the aims of using information on quality; (2) the interpretation of and
      preferences for the quality domains of safety, timeliness, effectiveness  and
      patient-centredness in relation to the user aims; and (3) the preferences for
      structure, process or outcome indicators. Content analysis was used to analyse
      qualitative data. RESULTS: Stakeholders had similar and different aims according
      to their roles. The interpretations of  quality domains varied greatly between
      the stakeholders. Besides differences in interpretation, their preferences were
      similar. Most stakeholders prioritised patient-centredness above the other
      domains of quality, ranked in order of priority as safety, effectiveness and
      timeliness, whereas  purchasers also prioritised efficiency. All stakeholders
      preferred to use process indicators or a mix of process and outcome indicators.
      CONCLUSIONS: The preferences of the stakeholders for quality indicators seem to
      be neither well-refined nor congruent. The implementation of an  indicator set
      can probably be improved if the stakeholders' definitions and preferences for
      quality domains become more explicit during the selection process for indicators.

PMID- 23113911
TI  - How prepared is the retirement and residential aged care sector in Western
      Australia for older non-heterosexual people?
AB  - OBJECTIVE: To explore attitudes, knowledge and current practices of retirement
      and residential aged care providers in Western Australia towards accommodating
      older gay, lesbian, bisexual, transgender and intersex (GLBTI) individuals. GLBTI
      is used throughout as a general term  to include people who are not exclusively
      heterosexual in identity, attraction and/or behaviour. METHODS: Postal surveys
      were sent to 329 providers of accommodation to ask about their attitudes,
      knowledge and current practices towards older GLBTI people. Two focus groups were
      also  held with managers of accommodation facilities and GLBTI community members.
      RESULTS: Few respondents reported having experience with any older GLBTI
      residents in their retirement or residential aged care facility. There was poor
      inclusion of GLBTI issues in policy frameworks, and  limited understanding
      regarding same-sex law reforms. CONCLUSION: Older non-heterosexual people are
      often obscured within ageing population discourses, and conceal their identity
      for fear of discrimination. GLBTI-sensitive practices can help to facilitate the
      disclosure of sexual  orientation and/or gender identity that may assist in
      meeting the unique needs of this group.

PMID- 23113912
TI  - Promoting diagnostic accuracy in general practitioner management of otitis media
      in children: findings from a multimodal, interactive workshop on tympanometry and
      pneumatic otoscopy.
AB  - AIM: Previous research has shown that general practitioners (GPs) rarely use
      pneumatic otoscopy or tympanometry as recommended by best practice guidelines for
      diagnosing otitis media. The purpose of this study was to determine whether a
      multimodal, interactive training workshop  on the techniques of pneumatic
      otoscopy and tympanometry would improve the confidence of GPs for the diagnosis
      of otitis media with effusion (OME) and acute otitis media (AOM), and for using
      pneumatic otoscopy and tympanometry. Additionally, we sought to determine whether
      this training could  change GPs' intentions for using pneumatic otoscopy and
      tympanometry in their practices. METHODS: Twenty-three GPs participated in a
      three-hour training workshop led by an ear, nose and throat (ENT) surgeon, a
      paediatrician and an audiologist. Prior to and following the workshop,  GPs
      completed questionnaires indicating their previous use and beliefs about the
      usefulness of pneumatic otoscopy and tympanometry, confidence for diagnosing AOM
      and OME, confidence for using pneumatic otoscopy and tympanometry, and intention
      to use pneumatic otoscopy and tympanometry in the  future. RESULTS: There were no
      differences (P > 0.05) from pre- to post-workshop in GP confidence for diagnosing
      AOM. There were increases in GP confidence for diagnosis of OME (pre: 4.5 +/-
      0.9, post: 4.9 +/- 0.4, P < 0.01) and confidence for using  pneumatic otoscopy
      (pre: 3.6 +/- 1.6, post: 4.8 +/- 1.0, P < 0.01) and tympanometry (pre: 3.3 +/-
      1.5, post: 5.0 +/- 0.7, P < 0.01), but no change (P > 0.05) in intention to use
      pneumatic otoscopy or tympanometry in their practices in the future. CONCLUSION:
      These results suggest that a multimodal, interactive workshop can significantly
      increase the confidence of GPs for diagnosis of OME and also for using pneumatic
      otoscopy and tympanometry. It is likely, however, that GPs will need follow-up
      and further practice with these techniques to implement  them in their practices.

PMID- 23113913
TI  - Symptom profile of undiagnosed obstructive sleep apnoea in hypertensive
      outpatients in primary care: a structural equation model analysis.
AB  - BACKGROUND: Obstructive sleep apnoea (OSA) has been linked to hypertension in
      sleep clinic populations, but little is known about the symptom profile of
      undiagnosed OSA in hypertensive outpatients in primary care. AIM: To explore
      characteristics associated with undiagnosed  OSA in hypertensive primary care
      patients. METHODS: Cross-sectional design, including 411 consecutive patients
      (52% women), mean age 57.9 years (standard deviation [SD] 5.9 years), with
      diagnosed hypertension (blood pressure >140/90 mmHg) from four primary care
      centres. All subjects  underwent a full-night, home-based, respiratory recording
      to establish the presence and severity of OSA. Clinical variables, medication and
      comorbidities, as well as data from self-rating scales regarding
      symptoms/characteristics, insomnia, excessive daytime sleepiness, depressive
      symptoms  and health were collected during a clinical examination. Factor
      analyses and structural equation modelling (SEM) were used to explore the
      relationships between self-rated symptoms, clinical characteristics and
      objectively verified diagnosis of OSA. MAIN OUTCOME: Measures symptom  profile of
      undiagnosed OSA (as measured by the Apnoea/Hypopnoea Index [AHI]) in hypertensive
      outpatients in primary care. RESULTS: Fifty-nine percent of the patients had an
      AHI >= 5/hour indicating OSA. An exploratory factor analysis based on 19
      variables yielded a six-factor model  (anthropometrics, blood pressure, OSA
      related symptoms, comorbidity, health complaints and physical activity)
      explaining 58% of the variance. SEM analyses showed strong significant
      associations between anthropometrics (body mass index, neck circumference, waist
      circumference) (0.45), OSA-related  symptoms (snoring, witnessed apnoeas, dry
      mouth) (0.47) and AHI. No direct effects of OSA on comorbidities, blood pressure,
      dyssomnia or self-rated health were observed. CONCLUSION: OSA was highly
      prevalent and was directly associated with anthropometrics and OSA-related
      symptoms  (snoring, witnessed apnoeas and dry mouth in the morning). When meeting
      patients with hypertension, these characteristics could be used by general
      practitioners to identify patients who are in need of referral to a sleep clinic
      for OSA evaluation.

PMID- 23113914
TI  - Rapid health impact assessment of aspirin promotion for the secondary prophylaxis
      of vascular events in Wales.
AB  - BACKGROUND: Evidence from two surveys in Wales, one of the countries of the
      United Kingdom, shows that there is an under-use of aspirin for secondary
      prophylaxis. A rapid health impact assessment of a policy of aspirin promotion in
      Wales is undertaken, with some estimates on  service provision. METHODS: In this
      analysis, a general population approach rather than gender-specific calculations
      was undertaken to estimate scale of magnitude. Readily available epidemiological
      data from the Welsh population was combined with effect estimates of aspirin
      derived  from randomised controlled trials (RCTs). RESULTS: An additional 700
      vascular events may be avoided annually, but the impact of aspirin promotion in
      the 30-45% of non-compliant individuals might range from 400 to 1200. This
      relates to about two vascular events being avoided  each day if aspirin were used
      at a maximum level, with 100% compliance. An individual general medical
      practitioner might case-find 25-35 individuals who should be taking aspirin
      regularly. DISCUSSION: The promotion of aspirin to post-vascular event
      individuals who are non-compliant  might be achieved through routine clinical
      management of patients. Person-centred approaches to improving compliance might
      be introduced.

PMID- 23113915
TI  - Improving interprofessional collaboration in primary care: position paper of the
      European Forum for Primary Care.
AB  - Primary care is the central pillar of health care. The increasingly complex
      health needs of the population and individual patients in a changing society can
      only be met by promoting interprofessional collaboration (IpC) within primary
      care teams. The aim of this Position Paper of the  European Forum for Primary
      Care (EFPC) is to analyse how to improve IpC within primary care teams.
      Clarification of the concept is the first step. Conditions to improve IpC are
      based on the education of healthcare professionals, adapting human resources, the
      occupational structure and the  skill-mix in primary care. These conditions,
      dependent on contextual factors, have a major influence on the development of
      IpC. They can be developed and organised at different levels: national, regional
      or team level. A framework is also needed to evaluate the level of collaboration
      within  teams. Examples of good practice throughout Europe issued from the EFPC
      network illustrate this.

PMID- 23113916
TI  - The influence of measurement error on calibration, discrimination, and overall
      estimation of a risk prediction model.
AB  - BACKGROUND: Self-reported height and weight are commonly collected at the
      population level; however, they can be subject to measurement error. The impact
      of this error on predicted risk, discrimination, and calibration of a model that
      uses body mass index (BMI) to predict risk of diabetes incidence is not known.
      The objective of this study is to use simulation to quantify and describe the
      effect of random and systematic error in self-reported height and weight on the
      performance of a model for predicting diabetes. METHODS: Two general categories
      of error were examined: random (nondirectional) error and systematic
      (directional) error on an algorithm relating BMI in kg/m2 to probability of
      developing diabetes. The cohort used to develop the risk algorithm was derived
      from 23,403 Ontario residents that responded to the 1996/1997 National Population
      Health Survey linked to a population-based diabetes registry. The data and
      algorithm were then simulated to allow for estimation of the impact of these
      errors on predicted risk using the Hosmer-Lemeshow goodness-of-fit chi2 and C
      statistic. Simulations were done 500 times with sample sizes of 9,177 for males
      and 10,618 for females. RESULTS: Simulation data successfully reproduced
      discrimination and calibration generated from population data. Increasing levels
      of random error in height and weight reduced the calibration and discrimination
      of the model. Random error biased the predicted risk upwards whereas systematic
      error biased predicted risk in the direction of the bias and reduced calibration;
      however, it did not affect discrimination. CONCLUSION: This study demonstrates
      that random and systematic errors in self-reported health data have the potential
      to influence the performance of risk algorithms. Further research that quantifies
      the amount and direction of error can improve model performance by allowing for
      adjustments in exposure measurements.

PMID- 23113917
TI  - The relationship between oral health education and quality of life in
      adolescents.
AB  - BACKGROUND: There is no study on the association between oral health education
      and oral health quality of life (OHQoL). AIM: To assess the relationship between
      oral health education activities integrated into primary care services and OHQoL
      in adolescents. DESIGN: A retrospective observational survey was conducted on 300
      randomly selected 12-14 years-of-age adolescents living in two publicly funded
      health service administrative areas in Manaus, Brazil. Between 2006 and 2008,
      dental treatment and oral health education were offered in one area (DT/OHE
      group), whereas in the other area, only dental treatment was provided (DT group).
      Collected data included socio-demographic characteristics, health services use,
      health-related behaviours, dental pain, dental caries and Child-OIDP. Independent
      variables were compared between groups by Mann-Whitney and chi-square tests. The
      association between one or more OIDP (Child-OIDP >= 1) and DT group tested using
      multivariate logistic regression. RESULTS: Caries, use of dental services and
      health-related behaviours did not differ between groups (P > 0.05). Child-OIDP >=
      1 was higher in DT group (90.0%) compared with DT/OHE group (79.3%) (P = 0.01).
      Child-OIDP >= 1 was independently associated with DT group [OR = 4.4 (1.1;
      17.0)]. CONCLUSIONS: Adolescents living in an area where OHE and DT were provided
      had better OHRQoL than those living in an area where only DT was provided.

PMID- 23113919
TI  - Improvement in coronary heart disease risk factors during an intermittent
      fasting/calorie restriction regimen: Relationship to adipokine modulations.
AB  - BACKGROUND: The ability of an intermittent fasting (IF)-calorie restriction (CR)
      regimen (with or without liquid meals) to modulate adipokines in a way that is
      protective against coronary heart disease (CHD) has yet to be tested. OBJECTIVE:
      Accordingly, we examined the effects of an IFCR diet on adipokine profile, body
      composition, and markers of CHD risk in obese women. METHODS: Subjects (n = 54)
      were randomized to either the IFCR-liquid (IFCR-L) or IFCR-food based (IFCR-F)
      diet for 10 weeks. RESULTS: Greater decreases in body weight and waist
      circumference were noted in the IFCR-L group (4 +/- 1 kg; 6 +/- 1 cm) versus the
      IFCR-F group (3 +/- 1 kg; 4 +/- 1 cm). Similar reductions (P < 0.0001) in fat
      mass were demonstrated in the IFCR-L (3 +/- 1 kg) and IFCR-F group (2 +/- 1 kg).
      Reductions in total and LDL cholesterol levels were greater (P = 0.04) in the
      IFCR-L (19 +/- 10%; 20 +/- 9%, respectively) versus the IFCR-F group (8 +/- 3%; 7
      +/- 4%, respectively). LDL peak particle size increased (P < 0.01) in the IFCR-L
      group only. The proportion of small LDL particles decreased (P < 0.01) in both
      groups. Adipokines, such as leptin, interleukin-6 (IL-6), tumor necrosis factor
      alpha (TNF-alpha), and insulin-like growth factor-1 (IGF-1) decreased (P < 0.05),
      in the IFCR-L group only. CONCLUSION: These findings suggest that IFCR with a
      liquid diet favorably modulates visceral fat and adipokines in a way that may
      confer protection against CHD.

PMID- 23113920
TI  - Organizing a dermatology service mission.
AB  - BACKGROUND: There are few published guidelines that describe the forethought and
      logistical considerations needed to create a dermatology-specific medical
      mission. OBJECTIVE: To report the experience of planning and executing a
      successful medical mission to an underserved community in Puerto Rico. METHODS:
      We identified an area of need and projected the volume of patients and diseases
      to be treated. After recruiting medical staff, pharmaceutical and surgical
      supplies were collected. Important concerns included establishing the scope of
      medical and educational services to be rendered, advertising the clinic,
      arranging for biopsy processing, ensuring follow-up, and selecting a method for
      medical documentation. We tracked the number of patients seen, diagnoses made,
      and materials used to prepare for future missions. RESULTS: We recruited 12
      physicians and 25 ancillary (i.e. nonlicensed physician) staff members,
      including: six dermatologists, four internists, one pathologist, one
      psychiatrist, 23 medical students, and two medical assistants. We secured 12
      examination rooms in an existing medical facility. Two pharmaceutical companies
      and two pathology companies provided the medications and surgical supplies with
      the remainder coming from the volunteer physicians' offices. Three thousand
      dollars were raised and used toward purchasing additional supplies. Advertising
      via public announcements resulted in the attendance of 166 patients during the 1
      day clinic. A total of 41 procedures were performed, including 14 biopsies, five
      excisions, three incisions and drainage, and 19 electrodessications and
      curettage. CONCLUSION: Proper planning is critical in creating a successful
      dermatology mission. Documenting the care given and supplies used helps to
      identify needs and optimize limited resources for future missions. The goal of a
      self-sustaining public health service starts with patient education and
      coordination with the local healthcare providers.

PMID- 23113918
TI  - Role of direct estrogen receptor signaling in wear particle-induced osteolysis.
AB  - Estrogen withdrawal following surgical ovariectomy was recently shown to mitigate
      particle-induced osteolysis in the murine calvarial model. Currently, we
      hypothesize that estrogen receptors (ERs) were involved in this paradoxical
      phenomenon. To test this hypothesis, we first evaluated polyethylene (PE)
      particle-induced osteolysis in the murine calvarial model, using wild type (WT)
      C57BL6J female mice, ERalpha deficient (ERalphaKO) mice, and WT mice either
      treated with 17beta-estradiol (E2) or with the ER pan-antagonist ICI 182,780.
      According to micro-CT and histomorphometry, we showed that bone resorption was
      consistently altered in both ERalphaKO and ICI 182,780 treated mice as compared
      to WT and E2 groups. Then, we demonstrated that ER disruption consistently
      decreased both PE and polymethylmethacrylate (PMMA) particle-induced production
      of TNF-alpha by murine macrophages in vitro. Similar results were obtained
      following ER blockade using ICI 182,780 in RAW 264.7 and WT macrophages. ER
      disruption and pre treatment with ICI 182,780 resulted in a consistent down
      regulation of particle-induced TNF-alpha mRNA expression relative to WT
      macrophages or untreated RAW cells. These results indicate that the response to
      wear particles involves estrogen receptors in female mice, as part of macrophage
      activation. Estrogen receptors may be considered as a future therapeutic target
      for particle-induced osteolysis.

PMID- 23113921
TI  - Curcumin and diabetes: a role for the vitamin D receptor?

PMID- 23113922
TI  - Biogenic amine production by the wine Lactobacillus brevis IOEB 9809 in systems
      that partially mimic the gastrointestinal tract stress.
AB  - BACKGROUND: Ingestion of fermented foods containing high levels of biogenic
      amines (BA) can be deleterious to human health. Less obvious is the threat posed
      by BA producing organisms contained within the food which, in principle, could
      form BA after ingestion even if the food product itself does not initially
      contain high BA levels. In this work we have investigated the production of
      tyramine and putrescine by Lactobacillus brevis IOEB 9809, of wine origin, under
      simulated gastrointestinal tract (GIT) conditions. RESULTS: An in vitro model
      that simulates the normal physiological conditions in the human digestive tract,
      as well as Caco-2 epithelial human cell lines, was used to challenge L. brevis
      IOEB 9809, which produced both tyramine and putrescine under all conditions
      tested. In the presence of BA precursors and under mild gastric stress, a
      correlation between enhancement of bacterial survival and a synchronous
      transcriptional activation of the tyramine and putrescine biosynthetic pathways
      was detected. High levels of both BA were observed after exposure of the
      bacterium to Caco-2 cells. CONCLUSIONS: L. brevis IOEB 9809 can produce tyramine
      and putrescine under simulated human digestive tract conditions. The results
      indicate that BA production may be a mechanism that increases bacterial survival
      under gastric stress.

PMID- 23113923
TI  - Recognizing misplacement of a dialysis catheter in the azygos vein.
AB  - Uneventful central venous catheterization for hemodialysis patients may not
      always result in a correct tip position. A case of inadvertent cannulation of the
      azygos vein is described. Radiographic features for its early recognition are
      emphasized and mechanisms related with azygos unintended catheterization are
      discussed. 

PMID- 23113924
TI  - Dienogest increases the progesterone receptor isoform B/A ratio in patients with
      ovarian endometriosis.
AB  - BACKGROUND: The resistance of endometriotic tissue to progesterone can be
      explained by alterations in the distribution of progesterone receptor (PR) and
      estrogen receptor (ER) isoforms. The aims of this study were to examine the
      expressions of PR-A, PR-B, ERalpha and ERbeta in endometrioma and assess whether
      these expressions are affected by dienogest or leuprolide acetate (LA) treatment.
      METHODS: We enrolled 60 females, including 43 patients with endometriosis (14 who
      received no medical treatment, 13 who received dienogest and 16 who received LA
      before undergoing laparoscopic surgery) and 17 patients with leiomyoma. The
      expression levels of PR and ER isoforms in eutopic and ectopic endometrium were
      assayed with quantitative real-time PCR, and confirmed with immunohistochemistry.
      RESULTS: A decreased PR-B/PR-A ratio and an increased ERbeta/ERalpha ratio were
      demonstrated in ectopic endometrium derived from females with endometriosis
      compared with the ratios observed in eutopic endometrium obtained from females
      without endometriosis. Although LA treatment did not affect the PR-B/PR-A and
      ERbeta/ERalpha ratios, dienogest treatment increased the PR-B/PR-A ratio and
      decreased the ERbeta/ERalpha ratio in patients with endometriomas. CONCLUSIONS:
      Dienogest may improve progesterone resistance in endometriotic tissue by
      increasing the relative expressions of PR-B and PR-A, and decreasing the relative
      expressions of ERbeta and ERalpha.

PMID- 23113925
TI  - Overweight according to geographical origin and time spent in France: a cross
      sectional study in the Paris metropolitan area.
AB  - BACKGROUND: For the first time in France in a population-based survey, this study
      sought to investigate the potential impact of migration origin and the proportion
      of lifetime spent in mainland France on body mass index (BMI) and overweight in
      adults living in the Paris metropolitan area. METHODS: A representative,
      population-based, random sample of the adult, French speaking population of the
      Paris metropolitan area was interviewed in 2005. Self-reported BMI (BMI =
      weight/height2) and overweight (BMI >= 25) were our 2 outcomes of interest. Two
      variables were constructed to estimate individuals' migration origin: parental
      nationality and the proportion of lifetime spent in mainland France, as declared
      by the participants. We performed multilevel regression models among different
      gender and age groups, adjusted for demographics and socioeconomic status.
      RESULTS: In women, a parental origin in the Middle East or North Africa (MENA)
      was associated with a higher risk of being overweight (especially before the age
      of 55) and a higher BMI (between 35 and 54 years of age), and so were women of
      Sub-Sahara African parental origin in the middle age category. Only in the
      youngest men (< 35 years of age) did we observe any association with parental
      nationality, with a higher BMI when having a MENA parentage. Regarding the
      association between the proportion of lifetime spent in France and overweight, we
      observed that, in women, a proportion of 50% to 99% appeared to be associated
      with overweight, especially after the age of 35. In men, having spent more than
      half of one's lifetime in France was associated with a higher risk of overweight
      among oldest men. CONCLUSIONS: Our results plea for potential cultural
      determinants of overweight in the migrant and migrants-born populations in the
      French context of the capital region. Taking into account the people' family and
      personal migration histories may be an important issue in public health research
      and policies on overweight and obesity prevention.

PMID- 23113926
TI  - Investigation of a prolonged APTT. Different approaches taken by laboratories to
      achieve the same diagnosis.
AB  - INTRODUCTION: The APTT is widely employed as part of a coagulation screening
      panel, used as a pre-operative assessment of bleeding risk, to detect hereditary
      and acquired haemostatic defects and to monitor anticoagulant therapy. External
      quality assessment (EQA) exercises assess laboratory performance of individual
      tests, but rarely assess the approach to investigation of an abnormal result.
      METHODS: A multicentre exercise was carried out to investigate the ability of
      laboratories to identify the cause of a prolonged APTT. A sample was distributed
      with a request to carry out whichever tests were considered necessary to achieve
      a probable diagnosis. RESULTS: One hundred and ten centres in the UK NEQAS
      programme took part, and all 104 centres providing an interpretation correctly
      identified deficiency of FVIII in the sample. However, of these, 10 centres
      reported additional defects, including lupus anticoagulant, FIX deficiency, FXII
      deficiency and a FVIII inhibitor. CONCLUSIONS: A markedly varied approach to
      investigation of a prolonged APTT was observed, although a lack of clinical
      information may have contributed to this finding.

PMID- 23113927
TI  - Vascular endothelial growth factor receptor-1 mRNA overexpression in peripheral
      blood as a useful prognostic marker in breast cancer.
AB  - INTRODUCTION: Identification of useful markers associated with poor prognosis in
      breast cancer patients is critically needed. We previously showed that expression
      of vascular endothelial growth factor receptor-1 mRNA in peripheral blood may be
      useful to predict distant metastasis in gastric cancer patients. However,
      expression of vascular endothelial growth factor receptor-1 mRNA in peripheral
      blood of breast cancer patients has not yet been studied. METHODS: Real-time
      reverse transcriptase-PCR was used to analyze vascular endothelial growth factor
      receptor-1 mRNA expression status with respect to various clinical parameters in
      515 patients with breast cancer and 25 controls. RESULTS: Expression of vascular
      endothelial growth factor receptor-1 mRNA in peripheral blood was higher in
      breast cancer patients than in controls. Increased vascular endothelial growth
      factor receptor-1 mRNA expression was associated with large tumor size, lymph
      node metastasis and clinical stage. Patients with high vascular endothelial
      growth factor receptor-1 mRNA expression also experienced a poorer survival rate
      than those with low expression levels, including those patients with triple
      negative type and luminal-HER2(-) type disease. CONCLUSIONS: Expression of
      vascular endothelial growth factor receptor-1 mRNA in peripheral blood may be
      useful for prediction of poor prognosis in breast cancer, especially in patients
      with triple-negative type and luminal-HER2(-) type disease.

PMID- 23113928
TI  - Training dual-task walking in community-dwelling adults within 1 year of stroke:
      a protocol for a single-blind randomized controlled trial.
AB  - BACKGROUND: Community ambulation is a highly complex skill requiring the ability
      to adapt to increased environmental complexity and perform multiple tasks
      simultaneously. After stroke, individuals demonstrate a diminished ability to
      perform dual-tasks. Current evidence suggests that conventional rehabilitation
      does not adequately address gait-related dual-task impairments after stroke,
      which may be contributing to low levels of participation and physical inactivity
      in community-dwelling stroke survivors. The objective of this study is to
      investigate the efficacy of dual-task gait training in community-dwelling adults
      within 1 year of stroke. Specifically, we will compare the effects of dual-task
      gait training and single-task gait training on cognitive-motor interference
      during walking at preferred speed and at fastest comfortable speed (Aim 1),
      locomotor control during obstacle negotiation (Aim 2), and spontaneous physical
      activity (Aim 3). METHODS/DESIGN: This single-blind randomized controlled trial
      will involve 44 individuals within 12 months of stroke. Following baseline
      evaluation, participants will be randomly allocated to single- or dual-task gait
      training. Both groups will receive 12, 30-minute sessions provided one-on-one
      over 4-6 weeks in an outpatient therapy setting. Single-task gait training
      involves practice of gait activities incorporating motor relearning principles.
      Dual-task gait training involves an identical gait training protocol; the
      critical difference being that the dual-task gait training group will practice
      the gait activities while simultaneously performing a cognitive task for 75% of
      the repetitions. Blinded assessors will measure outcomes at baseline, post
      intervention, and 6 months after completion of the intervention. The primary
      outcome measure will be dual-task effects on gait speed and cognition during
      unobstructed walking. Secondary outcomes include spatiotemporal and kinetic gait
      parameters during unobstructed single- and dual-task walking at preferred and
      fastest comfortable walking speeds, gait parameters during high and low obstacle
      crossing, spontaneous physical activity, executive function, lower extremity
      motor function, Timed Up and Go, balance self-efficacy, number of falls, and
      stroke-related disability. Hypotheses for each aim will be tested using an
      intention-to-treat analysis with repeated measures ANOVA design. DISCUSSION: This
      trial will provide evidence to help clinicians make decisions about the types of
      activities to include in rehabilitation to improve dual-task walking after
      stroke. TRIAL REGISTRATION: ClinicalTrials.gov NCT01568957.

PMID- 23113929
TI  - Systematic review of general burden of disease studies using disability-adjusted
      life years.
AB  - OBJECTIVE: To systematically review the methodology of general burden of disease
      studies. Three key questions were addressed: 1) what was the quality of the data,
      2) which methodological choices were made to calculate disability adjusted life
      years (DALYs), and 3) were uncertainty and risk factor analyses performed?
      Furthermore, DALY outcomes of the included studies were compared. METHODS: Burden
      of disease studies (1990 to 2011) in international peer-reviewed journals and in
      grey literature were identified with main inclusion criteria being multiple-cause
      studies that quantified the burden of disease as the sum of the burden of all
      distinct diseases expressed in DALYs. Electronic database searches included
      Medline (PubMed), EMBASE, and Web of Science. Studies were collated by study
      population, design, methods used to measure mortality and morbidity, risk factor
      analyses, and evaluation of results. RESULTS: Thirty-one studies met the
      inclusion criteria of our review. Overall, studies followed the Global Burden of
      Disease (GBD) approach. However, considerable variation existed in disability
      weights, discounting, age-weighting, and adjustments for uncertainty. Few studies
      reported whether mortality data were corrected for missing data or
      underreporting. Comparison with the GBD DALY outcomes by country revealed that
      for some studies DALY estimates were of similar magnitude; others reported DALY
      estimates that were two times higher or lower. CONCLUSIONS: Overcoming "error"
      variation due to the use of different methodologies and low-quality data is a
      critical priority for advancing burden of disease studies. This can enlarge the
      detection of true variation in DALY outcomes between populations or over time.

PMID- 23113931
TI  - R-wave synchronised atrial pacing in post-operative junctional ectopic
      tachycardia using a transoesophageal pacemaker.
AB  - We report the first case of R-wave synchronised atrial pacing using a
      transoesophageal pacemaker. A 3-month-old baby developed a junctional ectopic
      tachycardia after surgical closure of a ventricular septal defect. R-wave
      synchronised atrial pacing with an external pacemaker was not possible owing to
      dislocation of the atrial epimyocardial pacing wires. Therefore, a temporary
      oesophageal pacemaker was connected in series to the external pacemaker to allow
      transoesophageal atrial pacing triggered by the preceding ventricular actions.

PMID- 23113930
TI  - An automated workflow for enhancing microbial bioprocess optimization on a novel
      microbioreactor platform.
AB  - BACKGROUND: High-throughput methods are widely-used for strain screening
      effectively resulting in binary information regarding high or low productivity.
      Nevertheless achieving quantitative and scalable parameters for fast bioprocess
      development is much more challenging, especially for heterologous protein
      production. Here, the nature of the foreign protein makes it impossible to
      predict the, e.g. best expression construct, secretion signal peptide, inductor
      concentration, induction time, temperature and substrate feed rate in fed-batch
      operation to name only a few. Therefore, a high number of systematic experiments
      are necessary to elucidate the best conditions for heterologous expression of
      each new protein of interest. RESULTS: To increase the throughput in bioprocess
      development, we used a microtiter plate based cultivation system (Biolector)
      which was fully integrated into a liquid-handling platform enclosed in laminar
      airflow housing. This automated cultivation platform was used for optimization of
      the secretory production of a cutinase from Fusarium solani pisi with
      Corynebacterium glutamicum. The online monitoring of biomass, dissolved oxygen
      and pH in each of the microtiter plate wells enables to trigger sampling or
      dosing events with the pipetting robot used for a reliable selection of best
      performing cutinase producers. In addition to this, further automated methods
      like media optimization and induction profiling were developed and validated. All
      biological and bioprocess parameters were exclusively optimized at microtiter
      plate scale and showed perfect scalable results to 1 L and 20 L stirred tank
      bioreactor scale. CONCLUSIONS: The optimization of heterologous protein
      expression in microbial systems currently requires extensive testing of
      biological and bioprocess engineering parameters. This can be efficiently boosted
      by using a microtiter plate cultivation setup embedded into a liquid-handling
      system, providing more throughput by parallelization and automation. Due to
      improved statistics by replicate cultivations, automated downstream analysis, and
      scalable process information, this setup has superior performance compared to
      standard microtiter plate cultivation.

PMID- 23113932
TI  - The effect of osmolarity and caloric load on small bowel motility.
AB  - BACKGROUND: Although there is profound knowledge about cyclic fasting motility,
      the postprandial intestinal motor response is not well investigated. It is
      intriguing to speculate that nutrient composition alters small bowel motility
      significantly and, in a clinical setting, may account for adverse
      gastrointestinal symptoms in enteral nutrition (EN). We aimed to assess the
      impact of different caloric loads and osmolarities of EN on human jejunal
      motility. METHODS: Sixteen healthy subjects underwent a series of duodenal
      infusions of EN solutions, either with iso-osmolar solution with different
      caloric loads (1.32, 2.64, or 3.96 kcal min(-1)), or with solutions of different
      osmolarities with constant caloric loads (300, 600, or 1200 mosmol). Jejunal
      solid-state manometry was analyzed over 90 min both visually and using dedicated
      computer software. KEY RESULTS: All tested nutrient solutions were able to
      trigger conversion to a postprandial jejunal motility pattern after a mean lag
      phase of 9.4 + 2.3 min (P = NS between different nutrient solutions). Different
      caloric loads did not result in significant differences in small bowel motility.
      However, increasing osmolarities caused a significant inhibition of contractile
      and propagative activity. CONCLUSIONS & INFERENCES: Small bowel motility under
      duodenal infusion of nutrient solutions is not influenced by caloric load in a
      physiological range, whereas high osmolarities inhibit small bowel motility.

PMID- 23113933
TI  - Adult-onset Still's disease presenting lupus erythematosus-like facial erythema
      associated with Kikuchi's disease.

PMID- 23113934
TI  - Running interval training and estimated plasma-volume variation.
AB  - The effect of endurance interval training (IT) on hematocrit (Ht), hemoglobin
      (Hb), and estimated plasma- volume variation (PVV) in response to maximal
      exercise was studied in 15 male subjects (21.1 +/- 1.1 y; control group n = 6,
      and training group, n = 9). The training group participated in interval training
      3 times a week for 7 wk. A maximal graded test (GXT) was performed to determine
      maximal aerobic power (MAP) and maximal aerobic speed (MAS) both before and after
      the training program. To determine Ht, Hb concentration, and lactate
      concentrations, blood was collected at rest, at the end of GXT, and after 10 and
      30 min of recovery. MAP and MAS increased significantly (P < .05) after training
      only in training group. Hematocrit determined at rest was significantly lower in
      the training group than in the control group after the training period (P < .05).
      IT induced a significant increase of estimated PVV at rest for training group (P
      < .05), whereas there were no changes for control group. Hence, significant
      relationships were observed after training between PVV deter- mined at the end of
      the maximal test and MAS (r = .60, P < .05) and MAP (r = .76, P < .05) only for
      training group. In conclusion, 7 wk of IT led to a significant increase in plasma
      volume that possibly contributed to the observed increase of aerobic fitness (MAP
      and MAS). 

PMID- 23113935
TI  - Exploring care transitions from patient, caregiver, and health-care provider
      perspectives.
AB  - Care transitions involve coordination of patient care across multiple care
      settings. Many problems occur during care transitions resulting in negative
      patient outcomes and unnecessary readmissions. The purpose of this study was to
      describe the experience of care transitions from patient, caregiver, and health
      care provider perspectives in a single metropolitan Midwest city. A qualitative
      descriptive design was used to solicit patients', caregivers', and health-care
      providers' perceptions of care transitions, their role within the process,
      barriers to effective care transitions, and strategies to overcome these
      barriers. Five themes emerged: preplanned admissions are ideal; lack of needed
      patient information upon admission; multiple services are needed in preparing
      patients for discharge; rushed or delayed discharges lead to patient
      misunderstanding; and difficulties in following aftercare instructions. Findings
      illustrated provider difficulty in meeting multiple care needs, and the need for
      patient-centered care to achieve positive outcomes associated with quality
      measures, reduced readmissions, and care transitions. 

PMID- 23113936
TI  - Theta burst repetitive transcranial magnetic stimulation attenuates somatosensory
      evoked potentials from the lower limb.
AB  - BACKGROUND: Continuous theta burst stimulation (cTBS) is a form of repetitive
      transcranial magnetic stimulation which has been shown to alter cortical
      excitability in the upper limb representation of primary somatosensory cortex
      (SI). However, it is unknown whether cTBS modulates cortical excitability within
      the lower limb representation in SI. The present study investigates the effects
      of cTBS over the SI lower limb representation on cortical somatosensory evoked
      potentials (SEPs) and Hoffmann reflex (H-reflex) following tibial nerve
      stimulation at the knee. SEPs and H-reflex were recorded before and in four time
      blocks up to 30 minutes following cTBS targeting the lower limb representation
      within SI. RESULTS: Following cTBS, the P1-N1 first cortical potential was
      significantly decreased at 12-16 minutes. CTBS also suppressed the P2-N2 second
      cortical potential for up to 30 minutes following stimulation. The H-reflex
      remained statistically unchanged following cTBS although there was a modest
      suppression observed. CONCLUSION: We conclude that cTBS decreases cortical
      excitability of the lower limb representation of SI as evidenced by suppressed
      SEP amplitude. The duration and magnitude of the cTBS after effects are similar
      to those observed in upper limb studies.

PMID- 23113937
TI  - Directional preference following epidural steroid injection in three patients
      with acute cervical radiculopathy.
AB  - Cervical radiculopathy is typically characterized by neurologic symptoms that are
      traced to disturbances of discrete spinal nerve root(s) due to inflammatory or
      mechanical etiologies. Here we present three patients diagnosed with cervical
      radiculopathy, whose directional preference only surfaced after either a cervical
      transforaminal or intralaminar nerve root epidural steroid injection. This
      retrospective observational case series describes three men who presented with
      cervical radiculopathy with 7-9/10 neck pain, neck disability index (NDI) ranging
      between 44% and 90%, and an irreducible derangement upon McKenzie mechanical
      diagnosis and therapy (MMDT) evaluation. These patients demonstrated weaknesses,
      sensory changes, and/or decreased reflexes in the C5, C6, or C7 distributions.
      They each underwent a cervical transforaminal or intralaminar epidural injections
      at one or two levels, which uncovered their directional preference and
      facilitated further conservative treatment. These three patients experienced
      drastic improvements with each postinjection physical therapy session. They
      demonstrated decreased pain scores, centralization of pain, and a decreasing NDI
      trends throughout their treatments. They were all discharged with stable 0-3/10
      pain severity after four physical therapy sessions and NDI scores of 0%. These
      cases suggest an interplay between inflammatory and mechanical contributors to
      spine-mediated pain and the treatment challenge this presents. Dissecting the
      components of spine pain can be challenging; however, delivery of skilled
      multidisciplinary care in an algorithmic fashion may be beneficial and provide
      the future framework for the management of cervical radiculopathy and other spine
      related conditions. 

PMID- 23113938
TI  - Of mast and mean: differential-temperature cue makes mast seeding insensitive to
      climate change.
AB  - Mast-seeding plants often produce high seed crops the year after a warm spring or
      summer, but the warm-temperature model has inconsistent predictive ability. Here,
      we show for 26 long-term data sets from five plant families that the temperature
      difference between the two previous summers (DeltaT) better predicts seed crops.
      This discovery explains how masting species tailor their flowering patterns to
      sites across altitudinal temperature gradients; predicts that masting will be
      unaffected by increasing mean temperatures under climate change; improves
      prediction of impacts on seed consumers; demonstrates that strongly masting
      species are hypersensitive to climate; explains the rarity of consecutive high
      seed years without invoking resource constraints; and generates hypotheses about
      physiological mechanisms in plants and insect seed predators. For plants, DeltaT
      has many attributes of an ideal cue. This temperature-difference model clarifies
      our understanding of mast seeding under environmental change, and could also be
      applied to other cues, such as rainfall.

PMID- 23113939
TI  - A rule-based algorithm for automatic bond type perception.
AB  - Assigning bond orders is a necessary and essential step for characterizing a
      chemical structure correctly in force field based simulations. Several methods
      have been developed to do this. They all have advantages but with limitations
      too. Here, an automatic algorithm for assigning chemical connectivity and bond
      order regardless of hydrogen for organic molecules is provided, and only three
      dimensional coordinates and element identities are needed for our algorithm. The
      algorithm uses hard rules, length rules and conjugation rules to fix the
      structures. The hard rules determine bond orders based on the basic chemical
      rules; the length rules determine bond order by the length between two atoms
      based on a set of predefined values for different bond types; the conjugation
      rules determine bond orders by using the length information derived from the
      previous rule, the bond angles and some small structural patterns. The algorithm
      is extensively evaluated in three datasets, and achieves good accuracy of
      predictions for all the datasets. Finally, the limitation and future improvement
      of the algorithm are discussed.

PMID- 23113940
TI  - Infection, growth and maintenance of Wolbachia pipientis in clonal and non-clonal
      Aedes albopictus cell cultures.
AB  - Insect cell lines provide useful in vitro models for studying biological systems,
      including interactions between mosquitoes and obligate intracellular
      endosymbionts such as Wolbachia pipientis. The Aedes albopictus Aa23 cell line
      was the first cell line developed to allow examination of Wolbachia infections.
      However, Wolbachia studies using Aa23 can be complicated by the presence of
      different cell types in the cell line and the substantial temporal variation in
      infection level. Two approaches were examined to ameliorate infection
      variability. In the first approach, multiple Aa23 passaging regimes were tested
      for an effect on infection variability. Fluorescence in situ hybridization (FISH)
      staining was used to characterize Wolbachia infection level over time. The
      results demonstrate an impact of passaging method on Wolbachia infection level,
      with some methods resulting in loss of infection. None of the passaging methods
      succeeded in effectively mitigating infection level variation. In a second
      approach, the clonal C7-10 A. albopictus cell line was infected with Wolbachia
      from Aa23 cells and Drosophila simulans (Riverside), resulting in cell lines
      designated C7-10B and C7-10R, respectively. Characterization via FISH staining
      showed greater stability and uniformity of Wolbachia infection in C7-10R relative
      to the infection in C7-10B. Characterization of the Aa23, C7-10B and C7-10R lines
      is discussed as a tool for the study of Wolbachia-host cell interactions.

PMID- 23113941
TI  - Control of classical swine fever epidemics under varying conditions--with special
      focus on emergency vaccination and rapid PCR testing.
AB  - SUMMARY: In case of a classical swine fever outbreak in the European Union (EU),
      its control is based upon the culling of swine on infected farms, movement
      restrictions in the protection and surveillance zones, and contact tracing.
      Additionally, preventive culling may be carried out. Emergency vaccination and
      rapid PCR testing are discussed as alternatives to avoid this measure. An
      outbreak of classical swine fever and the success of its control are influenced
      by different factors. Using a spatial and temporal Monte-Carlo simulation model
      the control strategies 'Restriction Zone', 'Traditional Control', 'Emergency
      Vaccination', 'Test To Slaughter', 'Test To Control' and 'Vaccination in
      conjunction with Rapid Testing' were compared under various conditions. Farm
      density, compliance with movement restrictions and delay in the establishment of
      an emergency vaccination were analysed as influencing factors. It was found that
      all these factors had a significant influence on the number of infected and
      culled farms. In a low-density region, the basic measures are sufficient to
      control an epidemic, provided strict compliance with movement restrictions is
      adhered to. In a high-density region, additional measures are necessary. They can
      compensate non-strict compliance with movement restriction to a certain extent.
      In the high-density region, 'Emergency Vaccination' and 'Vaccination in
      conjunction with Rapid Testing' reached the same level of infected farms as
      'Traditional Control', independent of the value of compliance with movement
      restrictions. However, in the case of an emergency vaccination, an early start to
      the vaccination campaign is essential for successful disease control.

PMID- 23113942
TI  - Automated impedance-manometry analysis detects esophageal motor dysfunction in
      patients who have non-obstructive dysphagia with normal manometry.
AB  - BACKGROUND: Automated integrated analysis of impedance and pressure signals has
      been reported to identify patients at risk of developing dysphagia post
      fundoplication. This study aimed to investigate this analysis in the evaluation
      of patients with non-obstructive dysphagia (NOD) and normal manometry (NOD/NM).
      METHODS: Combined impedance-manometry was performed in 42 patients (27F : 15M;
      56.2 +/- 5.1 years) and compared with that of 24 healthy subjects (8F : 16M; 48.2
      +/- 2.9 years). Both liquid and viscous boluses were tested. MATLAB-based
      algorithms defined the median intrabolus pressure (IBP), IBP slope, peak pressure
      (PP), and timing of bolus flow relative to peak pressure (TNadImp-PP). An index
      of pressure and flow (PFI) in the distal esophagus was derived from these
      variables. KEY RESULTS: Diagnoses based on conventional manometric assessment:
      diffuse spasm (n = 5), non-specific motor disorders (n = 19), and normal (n =
      11). Patients with achalasia (n = 7) were excluded from automated impedance
      manometry (AIM) analysis. Only 2/11 (18%) patients with NOD/NM had evidence of
      flow abnormality on conventional impedance analysis. Several variables derived by
      integrated impedance-pressure analysis were significantly different in patients
      as compared with healthy: higher PNadImp (P < 0.01), IBP (P < 0.01) and IBP slope
      (P < 0.05), and shorter TNadImp_PP (P = 0.01). The PFI of NOD/NM patients was
      significantly higher than that in healthy (liquid: 6.7 vs 1.2, P = 0.02; viscous:
      27.1 vs 5.7, P < 0.001) and 9/11 NOD/NM patients had abnormal PFI. Overall, the
      addition of AIM analysis provided diagnoses and/or a plausible explanation in 95%
      (40/42) of patients who presented with NOD. CONCLUSIONS & INFERENCES: Compared
      with conventional pressure-impedance assessment, integrated analysis is more
      sensitive in detecting subtle abnormalities in esophageal function in patients
      with NOD and normal manometry.

PMID- 23113943
TI  - Systemic lupus erythematosus with flagellate erythema.

PMID- 23113944
TI  - Sex hormone changes during weight loss and maintenance in overweight and obese
      postmenopausal African-American and non-African-American women.
AB  - INTRODUCTION: Changes in sex hormones with weight loss might have implications
      for breast cancer prevention but have not been examined extensively, particularly
      in African-American (AA) women. METHODS: We conducted a prospective study of 278
      overweight/obese postmenopausal women (38% AA) not taking hormone therapy within
      the Weight Loss Maintenance Trial. All participants lost at least 4 kg after a 6
      month weight-loss phase and attempted to maintain weight loss during the
      subsequent 12 months. We evaluated the percentage changes in estrone, estradiol,
      free estradiol, testosterone, free testosterone, androstenedione,
      dehydroepiandrosterone sulfate and sex hormone-binding globulin (SHBG) using
      generalized estimating equations. RESULTS: In all study phases, AA women had
      higher levels of estrogen and testosterone concentrations, independent of
      adiposity. On average, participants lost 7.7 kg during the weight-loss phase, and
      concentrations of estrone (-5.7%, P = 0.006), estradiol (-9.9%, P <0.001), free
      estradiol (-13.4%, P <0.0001), and free testosterone (-9.9%, P <0.0001)
      decreased, while the SHBG concentration (16.2%, P <0.001) increased. Weight
      change did not significantly affect total testosterone or other androgen
      concentrations. Compared with non-AA women, AA women experienced less change in
      estrogens per kilogram of weight change (that is, per 1 kg weight loss: estrone, 
      0.6% vs. -1.2%, P-interaction = 0.10; estradiol, -1.1% vs. -1.9%, P-interaction =
      0.04; SHBG, 0.9% vs. 1.6%, P-interaction = 0.006; free estradiol, -1.4% vs. 
      2.1%, P-interaction = 0.01). CONCLUSION: To the best of our knowledge this is the
      first study to examine and compare the effects of intentional weight loss and
      maintenance on a panel of sex hormones in AA women and non-AA women. Although
      speculative, these data suggest hormonal differences may contribute to different
      racial patterns of breast cancer incidence and mortality and encourage further
      investigations to understand the long-term effects of weight loss on sex hormones
      in obese postmenopausal women. TRIAL REGISTRATION: ClinicalTrials.gov:
      NCT00054925.

PMID- 23113945
TI  - Alzheimer's disease biomarker discovery using in silico literature mining and
      clinical validation.
AB  - BACKGROUND: Alzheimer's Disease (AD) is the most widespread form of dementia in
      the elderly but despite progress made in recent years towards a mechanistic
      understanding, there is still an urgent need for disease modification therapy and
      for early diagnostic tests. Substantial international efforts are being made to
      discover and validate biomarkers for AD using candidate analytes and various data
      driven 'omics' approaches. Cerebrospinal fluid is in many ways the tissue of
      choice for biomarkers of brain disease but is limited by patient and clinician
      acceptability, and increasing attention is being paid to the search for blood
      based biomarkers. The aim of this study was to use a novel in silico approach to
      discover a set of candidate biomarkers for AD. METHODS: We used an in silico
      literature mining approach to identify potential biomarkers by creating a
      summarized set of assertional metadata derived from relevant legacy information.
      We then assessed the validity of this approach using direct assays of the
      identified biomarkers in plasma by immunodetection methods. RESULTS: Using this
      in silico approach, we identified 25 biomarker candidates, at least three of
      which have subsequently been reported to be altered in blood or CSF from AD
      patients. Two further candidate biomarkers, indicated from the in silico
      approach, were choline acetyltransferase and urokinase-type plasminogen activator
      receptor. Using immunodetection, we showed that, in a large sample set, these
      markers are either altered in disease or correlate with MRI markers of atrophy.
      CONCLUSIONS: These data support as a proof of concept the use of data mining and
      in silico analyses to derive valid biomarker candidates for AD and, by extension,
      for other disorders.

PMID- 23113946
TI  - Influence of oral glutamine supplementation on survival outcomes of patients
      treated with concurrent chemoradiotherapy for locally advanced non-small cell
      lung cancer.
AB  - BACKGROUND: Glutamine (Gln) supplementation during concurrent chemoradiotherapy
      (C-CRT) effectively reduces the incidence and severity of acute radiation-induced
      esophagitis (RIE). However, there are concerns that Gln might stimulate tumor
      growth, and therefore negatively impact the outcomes of anticancer treatment. We
      retrospectively investigated the effect of co-administration of oral Gln during C
      CRT on survival outcomes of patients with stage IIIB non-small cell lung
      carcinoma (NSCLC). We additionally evaluated role of oral Gln in preventing C-CRT
      induced weight change, acute and late toxicities. METHODS: The study included 104
      patients: 56 (53.8%) received prophylactic powdered Gln (Gln+) orally at a dose
      of 10 g/8 h and 48 (46.2%) did not receive Gln (Gln-) and served as controls. The
      prescribed radiation dose to the planning target volume was 66 Gy in 2-Gy
      fractions. Primary endpoints of progression-free survival (PFS), local/regional
      progression-free survival (LRPFS), and overall survival (OS) were correlated with
      status of Gln supplementation. RESULTS: Oral Gln was well tolerated except for
      mild nausea/vomiting in 14 (25.0%) patients. There was no C-CRT-related acute or
      late grade 4-5 toxicity. Administration of Gln was associated with a decrease in
      the incidence of grade 3 acute radiation-induced esophagitis (RIE) (7.2% vs.
      16.7% for Gln+ vs. Gln-; p=0.02) and late-RIE (0% vs. 6.3%; p=0.06), a reduced
      need for unplanned treatment breaks (7.1% vs. 20.8%; p=0.04), and reduced
      incidence of weight loss (44.6% vs. 72.9%; p=0.002). At a median follow-up of
      24.2 months (range 9.2-34.4) the median OS, LRPFS, and PFS for Gln+ vs. Gln-
      cohorts were 21.4 vs. 20.4 (p=0.35), 14.2 vs.11.3 (p=0.16), and 10.2 vs. 9.0
      months (p=0.11), respectively. CONCLUSION: In our study, supplementation with Gln
      during C-CRT had no detectable negative impact on tumor control and survival
      outcomes in patients with Stage IIIB NSCLC. Furthermore, Gln appeared to have a
      beneficial effect with respect to prevention of weight loss and unplanned
      treatment delays, and reduced the severity and incidence of acute- and late-RIE.

PMID- 23113948
TI  - Modelling fortification of corn masa flour with folic acid and the potential
      impact on Mexican-American women with lower acculturation.
AB  - OBJECTIVE: Hispanics with lower acculturation may be at higher risk for neural
      tube defects compared with those with higher acculturation due to lower total
      folic acid intake or other undetermined factors. Modelling has indicated that
      fortification of corn masa flour with folic acid could selectively target Mexican
      Americans more than other race/ethnicities. We assessed whether fortification of
      corn masa flour with folic acid could selectively increase folic acid intake
      among Mexican-American women with lower acculturation, as indicated by specific
      factors (language preference, country of origin, time living in the USA). DESIGN:
      We used dietary intake and dietary supplement data from the National Health and
      Nutrition Examination Survey 2001-2008, to estimate the amount of additional
      total folic acid that could be consumed if products considered to contain corn
      masa flour were fortified at 140 MUg of folic acid per 100 g of corn masa flour.
      SETTING: USA. SUBJECTS: Non-pregnant women aged 15-44 years (n 5369). RESULTS:
      Mexican-American women who reported speaking Spanish had a relative percentage
      change in usual daily total folic acid intake of 30.5 (95 % CI 27.8, 33.4) %,
      compared with 8.3 (95 % CI 7.3, 9.4) % for Mexican-American women who reported
      speaking English. We observed similar results for other acculturation factors. An
      increase of 6.0 percentage points in the number of Mexican-American women who
      would achieve the recommended intake of >=400 MUg folic acid/d occurred with
      fortification of corn masa flour; compared with increases of 1.1 percentage
      points for non-Hispanic whites and 1.3 percentage points for non-Hispanic blacks.
      An even greater percentage point increase was observed among Mexican-American
      women who reported speaking Spanish (8.2). CONCLUSIONS: Fortification of corn
      masa flour could selectively increase total folic acid intake among Mexican
      American women, especially targeting Mexican-American women with lower
      acculturation, and result in a decrease in the number of pregnancies affected by
      neural tube defects.

PMID- 23113947
TI  - Pyronaridine-artesunate granules versus artemether-lumefantrine crushed tablets
      in children with Plasmodium falciparum malaria: a randomized controlled trial.
AB  - BACKGROUND: Children are most vulnerable to malaria. A pyronaridine-artesunate
      pediatric granule formulation is being developed for the treatment of
      uncomplicated Plasmodium falciparum malaria. METHODS: This phase III, multi
      center, comparative, open-label, parallel-group, controlled clinical trial
      included patients aged <=12 years, bodyweight >=5 to <25 kg, with a reported
      history of fever at inclusion or in the previous 24 h and microscopically
      confirmed uncomplicated P. falciparum malaria. Patients were randomized (2:1) to
      pyronaridine-artesunate granules (60/20 mg) once daily or artemether-lumefantrine
      crushed tablets (20/120 mg) twice daily, both dosed by bodyweight, orally (liquid
      suspension) for three days. RESULTS: Of 535 patients randomized, 355 received
      pyronaridine-artesunate and 180 received artemether-lumefantrine. Day-28 adequate
      clinical and parasitological response (ACPR), corrected for re-infection using
      polymerase chain reaction (PCR) genotyping (per-protocol population) was 97.1%
      (329/339; 95% CI 94.6, 98.6) for pyronaridine-artesunate; 98.8% (165/167; 95% CI
      95.7, 99.9) for artemether-lumefantrine. The primary endpoint was achieved:
      pyronaridine-artesunate PCR-corrected day-28 ACPR was statistically significantly
      >90% (P < .0001). Pyronaridine-artesunate was non-inferior to artemether
      lumefantrine: treatment difference -1.8% (95% CI -4.3 to 1.6). The incidence of
      drug-related adverse events was 37.2% (132/355) with pyronaridine-artesunate,
      44.4% (80/180) with artemether-lumefantrine. Clinical biochemistry results showed
      similar mean changes versus baseline in the two treatment groups. From day 3
      until study completion, one patient in each treatment group had peak alanine
      aminotransferase (ALT) >3 times the upper limit of normal (ULN) and peak total
      bilirubin >2xULN (i.e. within the Hy's law definition). CONCLUSIONS: The
      pyronaridine-artesunate pediatric granule formulation was efficacious and was non
      inferior to artemether-lumefantrine. The adverse event profile was similar for
      the two comparators. Pyronaridine-artesunate should be considered for inclusion
      in paediatric malaria treatment programmes. TRIAL REGISTRATION:
      ClinicalTrials.gov: identifier NCT00541385.

PMID- 23113949
TI  - Exosomes and the kidney: blaming the messenger.
AB  - Exosomes are membrane-bound vesicles of endosomal origin, present in a wide range
      of biological fluids, including blood and urine. They range between 30 and 100 nm
      in diameter, and consist of a limiting lipid bilayer, transmembrane proteins and
      a hydrophilic core containing proteins, mRNAs and microRNAs (miRNA). Exosomes can
      act as extracellular vehicles by which cells communicate, through the delivery of
      their functional cargo to recipient cells, with many important biological,
      physiological and pathological implications. The exosome release pathway
      contributes towards protein secretion, antigen presentation, pathogen transfer
      and cancer progression. Exosomes and exosome-mediated signalling have been
      implicated in disease processes such as atherosclerosis, calcification and kidney
      diseases. Circulating levels of exosomes and extracellular vesicles can be
      influenced by the progression of renal disease. Advances in methods for
      purification and analysis of exosomes are leading to potential diagnostic and
      therapeutic avenues for kidney diseases. This review will focus on biophysical
      properties and biogenesis of exosomes, their pathophysiological roles and their
      potential as biomarkers and therapeutics in kidney diseases.

PMID- 23113951
TI  - Is there significant correlation between self-reported low back pain visual
      analogue scores and low back pain scores determined by pressure pain induction
      matching?
AB  - The objective of this study was to determine whether self-reported visual
      analogue scale (VAS) low back pain (LBP) scores are valid against matched
      psychophysically induced pressure pain scores. Two hundred thirty-six chronic LBP
      patients (some with neck pain) reported their LBP and neck pain scores on a VAS
      immediately before psychophysical pressure pain induction used to determine pain
      threshold (PTHRE), pain tolerance (PTOL), and a psychophysical pressure pain
      score which matched (PMAT) their current LBP. Pearson Product-Moment correlation
      coefficients were calculated between reported VAS neck scores, reported VAS LBP
      scores, and the psychophysically determined LBP PMAT scores. The PMAT scores were
      calculated utilizing PTOL only and both PTOL and PTHRE. There was a significant
      correlation between the LBP PMAT scores and the reported LBP VAS scores for both
      types of psychophysical LBP PMAT score calculations; however, there were
      insignificant correlations between the LBP PMAT scores and reported neck VAS
      scores. Chronic LBP patients can match their self-reported VAS LBP scores to
      psychophysically determined LBP PMAT scores. As such, self-reported VAS chronic
      LBP scores appear to be valid against one type of psychophysical measurement.

PMID- 23113950
TI  - Morphological and behavioural changes occur following the X-ray irradiation of
      the adult mouse olfactory neuroepithelium.
AB  - BACKGROUND: The olfactory neuroepithelium lines the upper nasal cavity and is in
      direct contact with the external environment and the olfactory bulbs. The ability
      to self-renew throughout life and the reproducible recovery after injury, make it
      a model tissue to study mechanisms underlying neurogenesis. In this study, X-rays
      were used to disrupt proliferating olfactory stem cell populations and to assess
      their role in the cellular and morphological changes involved in olfactory
      neurogenic processes. RESULTS: We have analysed the histological and functional
      effects of a sub-lethal dose of X-rays on the adult mouse olfactory
      neuroepithelium at 2 hours, 24 hours, 1 week, 2 weeks and 5 weeks. We have shown
      an immediate cessation of proliferating olfactory stem cells as shown by BrdU,
      Ki67 and pH3 expression. At 24 hours there was an increase in the neural
      transcription factors Mash1 and Pax6 expression, and a disruption of the basal
      lamina and increase in glandular cell marker expression at 1 week post
      irradiation. Coincident with these changes was an impairment of the olfactory
      function in vivo. CONCLUSIONS: We have shown significant changes in basal cell
      proliferation as well as morphological changes in the olfactory neuroepithelium
      following X-ray irradiation. There is involvement of the basal lamina as well as
      a clear role for glandular and sustentacular cells.

PMID- 23113952
TI  - Rapidity of response to hypoxic conditions during exercise.
AB  - Previous studies have found decreases in arterial oxygen saturation to be
      temporally linked to reductions in power output (PO) during time-trial (TT)
      exercise. The purpose of this study was to determine whether preexercise
      desaturation (estimated from pulse oximetry [SpO2]), via normobaric hypoxia,
      would change the pattern of PO during a TT. PURPOSE: The authors tested the
      hypothesis that the starting PO of a TT would be reduced in the EARLY trial
      secondary to a reduced SpO2 but would not be reduced in LATE until ~30 s after
      the start of the TT. METHODS: Eight trained cyclists/triathletes (4 male, 4
      female) performed 3 randomly ordered 3-km TTs while breathing either room air
      (CONTROL) or hypoxic air administered 3 min before the start of the TT (EARLY) or
      at the beginning of the TT (LATE). RESULTS: There was no effect of hypoxia on PO
      during the first 0.3 km of either the EARLY or the LATE trial compared with
      CONTROL, although there was a significant decrease in pre-TT SpO2 in EARLY vs
      CONTROL and LATE. The time for PO to decrease was ~40 s after the start of the TT
      in both EARLY and LATE. CONCLUSIONS: The results support the strong effect of the
      preexercise template on the pattern of PO during simulated competition and
      suggest that reductions in SpO2 are not direct signals to decrease PO.

PMID- 23113953
TI  - Effects of guaifenesin, N-acetylcysteine, and ambroxol on MUC5AC and mucociliary
      transport in primary differentiated human tracheal-bronchial cells.
AB  - BACKGROUND: Therapeutic intervention in the pathophysiology of airway mucus
      hypersecretion is clinically important. Several types of drugs are available with
      different possible modes of action. We examined the effects of guaifenesin (GGE),
      N-acetylcysteine (NAC) and ambroxol (Amb) on differentiated human airway
      epithelial cells stimulated with IL-13 to produce additional MUC5AC. METHODS:
      After IL-13 pre-treatment (3 days), the cultures were treated with GGE, NAC or
      Amb (10-300 MUM) in the continued presence of IL-13. Cellular and secreted
      MUC5AC, mucociliary transport rates (MTR), mucus rheology at several time points,
      and the antioxidant capacity of the drugs were assessed. RESULTS: IL-13 increased
      MUC5AC content (~25%) and secretion (~2-fold) and decreased MTR, but only
      slightly affected the G' (elastic) or G" (viscous) moduli of the secretions. GGE
      significantly inhibited MUC5AC secretion and content in the IL-13-treated cells
      in a concentration-dependent manner (IC50s at 24 hr ~100 and 150 MUM,
      respectively). NAC or Amb were less effective. All drugs increased MTR and
      decreased G' and G" relative to IL-13 alone. Cell viability was not affected and
      only NAC exhibited antioxidant capacity. CONCLUSIONS: Thus, GGE effectively
      reduces cellular content and secretion of MUC5AC, increases MTR, and alters mucus
      rheology, and may therefore be useful in treating airway mucus hypersecretion and
      mucostasis in airway diseases.

PMID- 23113954
TI  - Beta-diversity in temperate and tropical forests reflects dissimilar mechanisms
      of community assembly.
AB  - Site-to-site variation in species composition (beta-diversity) generally
      increases from low- to high-diversity regions. Although biogeographical
      differences in community assembly mechanisms may explain this pattern, random
      sampling effects can create this pattern through differences in regional species
      pools. Here, we compared assembly mechanisms between spatially extensive networks
      of temperate and tropical forest plots with highly divergent species pools (46
      vs. 607 species). After controlling for sampling effects, beta-diversity of woody
      plants was similar and higher than expected by chance in both forests, reflecting
      strong intraspecific aggregation. However, different mechanisms appeared to
      explain aggregation in the two forests. In the temperate forest, aggregation
      reflected stronger environmental correlations, suggesting an important role for
      species-sorting (e.g. environmental filtering) processes, whereas in the tropics,
      aggregation reflected stronger spatial correlations, more likely reflecting
      dispersal limitation. We suggest that biogeographical differences in the relative
      importance of different community assembly mechanisms contribute to these
      striking gradients in global biodiversity.

PMID- 23113955
TI  - Effectiveness of a proactive mail-based alcohol Internet intervention for
      university students: dismantling the assessment and feedback components in a
      randomized controlled trial.
AB  - BACKGROUND: University students in Sweden routinely receive proactive mail-based
      alcohol Internet interventions sent from student health services. This
      intervention provides personalized normative feedback on alcohol consumption with
      suggestions on how to decrease drinking. Earlier feasibility trials by our group
      and others have examined effectiveness in simple parallel-groups designs.
      OBJECTIVE: To evaluate the effectiveness of electronic screening and brief
      intervention, using a randomized controlled trial design that takes account of
      baseline assessment reactivity (and other possible effects of the research
      process) due to the similarity between the intervention and assessment content.
      The design of the study allowed for exploration of the magnitude of the
      assessment effects per se. METHODS: This trial used a dismantling design and
      randomly assigned 5227 students to 3 groups: (1) routine practice assessment and
      feedback, (2) assessment-only without feedback, and (3) neither assessment nor
      feedback. At baseline all participants were blinded to study participation, with
      no contact being made with group 3. We approached students 2 months later to
      participate in a cross-sectional alcohol survey. All interventions were fully
      automated and did not have any human involvement. All data used in the analysis
      were based on self-assessment using questionnaires. The participants were unaware
      that they were participating in a trial and thus were also blinded to which group
      they were randomly assigned. RESULTS: Overall, 44.69% (n = 2336) of those
      targeted for study completed follow-up. Attrition was similar in groups 1
      (697/1742, 40.01%) and 2 (737/1742, 42.31% retained) and lower in group 3
      (902/1743, 51.75% retained). Intention-to-treat analyses among all participants
      regardless of their baseline drinking status revealed no differences between
      groups in all alcohol parameters at the 2-month follow-up. Per-protocol analyses
      of groups 1 and 2 among those who accepted the email intervention (36.2% of the
      students who were offered the intervention in group 1 and 37.3% of the students
      in group2 ) and who were risky drinkers at baseline (60.7% follow-up rate in
      group 1 and 63.5% in group 2) suggested possible small beneficial effects on
      weekly consumption attributable to feedback. CONCLUSIONS: This approach to
      outcome evaluation is highly conservative, and small benefits may follow the
      actual uptake of feedback intervention in students who are risky drinkers, the
      precise target group. TRIAL REGISTRATION: International Standard Randomized
      Controlled Trial Number (ISRCTN): 24735383; http://www.controlled
      trials.com/ISRCTN24735383 (Archived by WebCite at
      http://www.webcitation.org/6Awq7gjXG).

PMID- 23113957
TI  - Advancing the science of ventilator-associated pneumonia surveillance.
AB  - The landmark Study on the Efficacy of Nosocomial Infection Control definitively
      demonstrated that infection surveillance and control programs prevent hospital
      acquired infections. The rise of public reporting, benchmarking, and pay for
      performance movements, however, has considerably changed the infection
      surveillance landscape in the 27 years since this study was published. Clinically
      nuanced surveillance definitions that served the profession well for many years
      have fallen into disfavor because their complexity and subjectivity allow for
      conscious and subconscious gaming. These limitations make it very difficult to
      determine whether changes in surveillance rates represent true changes in disease
      incidence or artifacts of definition subjectivity, external reporting pressures,
      and internal biases. Surveillance definitions need to be revised to enhance
      objectivity and to ensure that they detect clinically meaningful events
      associated with compromised outcomes. The US Centers for Disease Control and
      Prevention recently released modified definitions for ventilator-associated
      events that have the potential to make safety surveillance for ventilated
      patients more credible and useful once again. 

PMID- 23113956
TI  - National trends in beverage consumption in children from birth to 5 years:
      analysis of NHANES across three decades.
AB  - BACKGROUND: Given the epidemic of childhood obesity, it is crucial to assess food
      and beverage intake trends. Beverages can provide a large number of calories and
      since consumption patterns seem to develop at a young age we examined beverage
      consumption trends over three decades. The objective of this study was to assess
      the beverage (milk, fruit juice, fruit drinks, tea, soy beverages, and soft
      drinks) consumption trends in children <1-5 years of age. METHODS: Data from
      individuals ages <1-5 years participating in the National Health and Nutrition
      Examination Survey (NHANES) from 1976-1980, 1988-1994 and 2001-2006 were used to
      assess beverage consumption and associated calorie and nutrient intakes. RESULTS:
      During the NHANES 1976-1980 and 1988-1994 periods, approximately 84-85% of
      children were consuming milk, whereas only 77% were consuming milk during NHANES
      2001-2006. Flavored milk intake was relatively low, but increased to 14% during
      the last decade (p < 0.001). Fruit juice consumption increased dramatically
      during NHANES 2001-2006 to more than 50% of the population compared to about 30%
      in the older surveys (p < 0.001). No significant changes were observed in fruit
      drink intake across all three decades with 35-37% of this population consuming
      fruit drinks. At least 30% of children consumed soft drinks. Milk was the largest
      beverage calorie contributor in all three decades surveyed and was the primary
      contributor of calcium (52-62%), phosphorus (37-42%), magnesium (27-28%), and
      potassium (32-37%). Fruit juice and fruit drinks each provided 8-10% of calories
      with soft drinks providing 5-6% of calories. Fruit juice was an important
      provider of potassium (16-19%) and magnesium (11%). Fruit drinks provided less
      than 5% of nutrients examined and soft drinks provided very little of the
      nutrients evaluated. CONCLUSIONS: Given concerns about childhood obesity and the
      need to meet nutrition requirements, it is prudent that parents, educators and
      child caretakers replace some of the nutrient poor beverages young children are
      currently consuming with more nutrient dense sources like low-fat and fat-free
      milk.

PMID- 23113959
TI  - Effects of an intense, high-frequency laser field on bound states in Ga1 -
      xInxNyAs1 - y/GaAs double quantum well.
AB  - Within the envelope function approach and the effective-mass approximation, we
      have investigated theoretically the effect of an intense, high-frequency laser
      field on the bound states in a GaxIn1 - xNyAs1 - y/GaAs double quantum well for
      different nitrogen and indium mole concentrations. The laser-dressed potential,
      bound states, and squared wave functions related to these bound states in Ga1 -
      xInxNyAs1 - y/GaAs double quantum well are investigated as a function of the
      position and laser-dressing parameter. Our numerical results show that both
      intense laser field and nitrogen (indium) incorporation into the GaInNAs have
      strong influences on carrier localization.

PMID- 23113958
TI  - Validation and reproducibility of an FFQ for use among adults in Botswana.
AB  - OBJECTIVE: To evaluate the validity and reproducibility of a 122-item interviewer
      administered quantitative FFQ developed to determine food and nutrient intakes of
      adults in Botswana. DESIGN: Relative validity of the FFQ was evaluated by
      comparing nutrient and food group intakes against four non-consecutive 24 h
      recalls administered over 12 months. The FFQ was repeated after 1 year to assess
      reproducibility. SETTING: Kanye, Botswana. SUBJECTS: Seventy-nine adults aged 18
      75 years. RESULTS: Spearman correlation coefficients for the validity of energy
      adjusted nutrients ranged from 0.42 (carbohydrate) to 0.49 (protein) for
      macronutrients and from 0.23 (Fe) to 0.44 (PUFA) for micronutrients. Exact
      agreement of quartile distribution for nutrients between the FFQ and recalls
      ranged from 27% to 72%. Weighted kappa values were lowest for retinol (0.13), Fe
      (0.22) and b-carotene (0.25) and ranged from 0.33 (SFA) to 0.59 (folate) for
      other nutrients (energy, carbohydrate, protein, fat, Ca and vitamin E). Spearman
      correlation coefficients between the recalls and FFQ for food groups ranged from
      0.18 (dark green leafy and yellow vegetables) to 0.58 (poultry). Reproducibility
      correlation coefficients (energy-adjusted) varied between 0.39 for retinol and
      0.66 for vitamin E, with most values falling between 0.50 and 0.60. CONCLUSIONS:
      The FFQ had good relative validity for estimating habitual food group and
      nutrient intakes, but was poor for some micronutrients (Fe, retinol and b
      carotene) and foods (fruits and dark green leafy vegetables).

PMID- 23113960
TI  - Sharing schistosomes: the elephant schistosome Bivitellobilharzia nairi also
      infects the greater one-horned rhinoceros (Rhinoceros unicornis) in Chitwan
      National Park, Nepal.
AB  - Because the digenetic trematode fauna of Nepal is poorly known, we began to
      search for schistosomes in and around Chitwan National Park (CNP) of southern
      Nepal. Both domestic and wild Indian elephants (Elephus maximus) are present, and
      we found one of two dung samples from wild elephants and 1 of 22 (4.5%) dung
      samples from domestic elephants to be positive for schistosome eggs. The
      morphology of the eggs and both cox1 and 28S sequences derived from the
      eggs/miracidia were consistent with Bivitellobilharzia nairi, reported here for
      the first time from Nepal. Also, 7 of 14 faecal samples from the Asian or greater
      one-horned rhinoceros (Rhinoceros unicornis) contained viable eggs
      indistinguishable from those of B. nairi. This identification was confirmed by
      comparison with both cox1 and 28S sequences from B. nairi eggs/miracidia derived
      from Nepalese and Sri Lankan elephants. This represents the first sequence
      verified identification of a schistosome from any species of rhinoceros, and the
      first verified occurrence of a representative of Bivitellobilharzia (a genus of
      'elephant schistosomes') in mammals other than elephants. Our work suggests that
      elephants and rhinos share B. nairi in CNP, even though these two members of the
      'charismatic megafauna' belong to unrelated mammalian families. Their shared life
      style of extensive contact with freshwater habitats likely plays a role, although
      the snail intermediate host and mode of definitive host infection for B. nairi
      have yet to be documented. This report also supports Bivitellobilharzia as a
      monophyletic group and its status as a distinct genus within Schistosomatidae. 

PMID- 23113961
TI  - Individualization of time-motion analysis: a case-cohort example.
AB  - PURPOSE: To report the intensity distribution of Premier League soccer players'
      external loads during match play, according to recognized physiological
      thresholds. The authors also present a case in which individualized speed
      thresholds changed the interpretation of time-motion data. METHOD: Eight outfield
      players performed an incremental treadmill test to exhaustion to determine the
      running speeds associated with their ventilatory thresholds. The running speeds
      were then used to individualize time-motion data collected in 5 competitive
      fixtures and compared with commonly applied arbitrary speed zones. RESULTS: Of
      the total distance covered, 26%, 57%, and 17% were performed at low, moderate,
      and high intensity, respectively. Individualized time-motion data identified a
      41% difference in the high-intensity distance covered between 2 players of the
      same positional role, whereas the player-independent approach yielded negligible
      (5-7%) differences in total and high-speed distances covered. CONCLUSIONS: The
      authors recommend that individualized speed thresholds be applied to time-motion
      analysis data in synergy with the traditional arbitrary approach.

PMID- 23113963
TI  - Viscosity of electrolyte solutions: a mode-coupling theory.
AB  - We present a versatile theoretical method for calculating the steady-state
      viscosity and shear relaxation function of strong electrolyte solutions. In this
      method, the ions are described on a primitive model level as charged Brownian
      spheres, and the essential ion-ion hydrodynamic interactions (HIs) are accounted
      for in the shear relaxation effect of the ionic atmosphere. The method combines a
      many-component mode-coupling theory (MCT) approach by Nagele et al (1998 J. Chem.
      Phys. 108 9893) with a simplified solution scheme, leading to an analytic
      expression for the shear relaxation contribution to the viscosity. This
      expression accounts for both the excluded volumes of the ions and their HIs. We
      show that the limiting law results for the viscosity of electrolyte mixtures by
      Falkenhagen and by Onsager and Fuoss are recovered at very low concentrations,
      and we discuss HIs corrections appearing at higher concentrations. Our numerical
      results for a 1:1 electrolyte reveal a strong enlargement of the viscosity caused
      by the HIs. The high-frequency viscosity gives the largest contribution to the
      total viscosity at higher concentrations.

PMID- 23113962
TI  - Assessing the effect of CT slice interval on unidimensional, bidimensional and
      volumetric measurements of solid tumours.
AB  - OBJECTIVES: To study the magnitude of differences in tumour unidimensional (1D),
      bidimensional (2D) and volumetric (VOL) measurements determined from computed
      tomography (CT) images reconstructed at 5, 2.5 and 1.25 mm slice intervals.
      MATERIALS AND METHODS: A total of 118 lesions in lung, liver and lymph nodes were
      selected from 30 patients enrolled in early phase clinical trials. Each CT scan
      was reconstructed at 5, 2.5 and 1.25 mm slice intervals during the image
      acquisition. Lesions were semi-automatically segmented on each interval image
      series and supervised by a radiologist. 1D, 2D and VOL were computed based on the
      final segmentation results. Average measurement differences across different
      slice intervals were obtained using linear mixed-effects analysis of variance
      models. RESULTS: Lesion diameters ranged from 6.1 to 80.1 mm (median 18.4 mm).
      The largest difference was seen between 1.25 and 5 mm (mean difference of 7.6%
      for 1D [P < 0.0001], 13.1% for 2D [P < 0.0001], -5.7% for VOL [P = 0.0001]). Mean
      differences between 1.25 and 2.5 mm were all within +/-3.5% (within +/-6%
      confidence interval). For VOL, there was a larger average difference between
      measurements on different slice intervals for the smaller lesions (<10 mm)
      compared with the larger lesions. CONCLUSIONS: Different slice intervals may give
      different 1D, 2D and VOL measurements. In clinical practice, it would be prudent
      to use the same slice interval for consecutive measurements.

PMID- 23113964
TI  - The long-term efficacy and safety of percutaneous cervical nucleoplasty in
      patients with a contained herniated disk.
AB  - BACKGROUND: Percutaneous cervical nucleoplasty (PCN) is a safe and effective
      treatment in symptomatic patients with contained cervical herniated disks. It
      provides simple and efficient disk decompression, using a controlled and highly
      localized ablation, but evidence regarding long-term efficacy is limited. We
      conducted a retrospective study to investigate the long-term efficacy and safety
      of PCN, and the influence of ideal selection settings. METHODS: A total of 27
      patients treated with PCN fulfilling ideal selection criteria (Group A) were
      studied and compared to 42 patients not meeting these criteria (Group B).
      Outcomes were assessed using the Visual Analogue Scale (VAS) and a four-level
      Likert item for perceived pain and satisfaction, the Neck Disability Index (NDI),
      and the Short Form 36 (SF-36). Additional relevant outcomes were retrieved from
      medical records. RESULTS: The postoperative mean VAS pain for Group A was 29.9
      (SD +/- 32.6) at a mean follow-up of 24 months (range: 2-45). Only 10% of these
      patients reported mild transient adverse events. There was a trend, but no
      difference between both groups in pain scores; however, treatment satisfaction
      was higher for Group A (74.1 +/- 27.2-55.5 +/- 31.4, P = 0.02). Group A also
      reported better physical functioning based on the Physical Component Summary
      (43.6 +/- 10.6-37.3 +/- 12.0, P = 0.03) and showed a larger proportion of
      patients no longer using any medication postoperatively (63-26%, P = 0.01).
      CONCLUSION: These results show long-term effectiveness and safety of PCN in
      patients with a one-level contained cervical herniated disk, and the reliance of
      selecting patients meeting ideal criteria for successful PCN.

PMID- 23113965
TI  - Effects of manidipine plus rosuvastatin versus olmesartan plus rosuvastatin on
      markers of insulin resistance in patients with impaired fasting glucose,
      hypertension, and mixed dyslipidemia.
AB  - AIM: To compare the effect of manidipine 20 mg plus rosuvastatin 10 mg versus
      olmesartan 20 mg plus rosuvastatin 10 mg on markers of insulin resistance in
      patients with mixed dyslipidemia, hypertension, and impaired fasting glucose
      (IFG). METHODS: This study had a prospective, randomized, open-label, blinded
      endpoint (PROBE) design. A total of 40 patients with IFG, mixed dyslipidemia, and
      stage 1 hypertension were included. Following dietary intervention, patients were
      randomly allocated to rosuvastatin (10 mg/d) plus olmesartan (20 mg/d) or
      manidipine (20 mg/d). The primary end point was the between-group difference in
      changes in the Homeostasis Model Assessment Insulin Resistance (HOMA-IR) index
      following 3 months of treatment. Secondary end points included changes in fasting
      plasma glucose (FPG), fasting insulin levels, and glucosylated hemoglobin.
      RESULTS: At the end of the 3-month treatment period, a significant increase in
      HOMA-IR index by 14% (from 2.4 [0.5-7.9] to 2.7 [0.5-5.2], P = .02 versus
      baseline) was seen in the olmesartan plus rosuvastatin group. On the contrary, no
      significant change in HOMA-IR index was observed in the manidipine plus
      rosuvastatin group (1.7 [0.5-5.2] to 1.7 [0.8-6.0], P = NS versus baseline, P =
      .04 versus olmesartan plus rosuvastatin group). An increase in fasting insulin
      levels was observed in the olmesartan plus rosuvastatin group (+8%, from 10.1
      [2.0-29.6] to 10.9 [2.0-19.1] MUU/mL, P < .05 versus baseline), while no
      significant change was seen in the manidipine plus rosuvastatin group (+3%, from
      7.3 [2.0-17.6] to 7.5 [1.9-15.6] MUU/mL, P = NS versus baseline, P = .02 versus
      olmesartan plus rosuvastatin group). Fasting plasma glucose and glycosylated
      hemoglobin did not change significantly in any group. CONCLUSION: Manidipine
      seems to ameliorate the possible statin-associated increase in insulin resistance
      as compared with olmesartan in patients with IFG, hypertension, and mixed
      dyslipidemia.

PMID- 23113966
TI  - 16S rRNA survey revealed complex bacterial communities and evidence of bacterial
      interference on human adenoids.
AB  - Adenoid microbiota plays an important role in the development of various
      infectious and non-infectious diseases of the upper airways, such as otitis
      media, adenotonsillitis, rhinosinusitis and adenoid hypertrophy. Studies have
      suggested that adenoids could act as a potential reservoir of opportunistic
      pathogens. However, previous bacterial surveys of adenoids were mainly culture
      based and therefore might only provide an incomplete and potentially biased
      assessment of the microbial diversity. To develop an in-depth and comprehensive
      understanding of the adenoid microbial communities and test the 'pathogen
      reservoir hypothesis', we carried out a 16S rRNA based, culture-independent
      survey of bacterial communities on 67 human adenoids removed by surgery. Our
      survey revealed highly diverse adenoid bacterial communities distinct from those
      of other body habitats. Despite large interpersonal variations, adenoid
      microbiota shared a core set of taxa and can be classified into at least five
      major types based on its bacterial species composition. Our results support the
      'pathogen reservoir hypothesis' as we found common pathogens of otitis media to
      be both prevalent and abundant. Co-occurrence analyses revealed evidence
      consistent with the bacterial interference theory in that multiple common
      pathogens showed 'non-coexistence' relationships with non-pathogenic members of
      the commensal microflora.

PMID- 23113967
TI  - Denoising PCR-amplified metagenome data.
AB  - BACKGROUND: PCR amplification and high-throughput sequencing theoretically enable
      the characterization of the finest-scale diversity in natural microbial and viral
      populations, but each of these methods introduces random errors that are
      difficult to distinguish from genuine biological diversity. Several approaches
      have been proposed to denoise these data but lack either speed or accuracy.
      RESULTS: We introduce a new denoising algorithm that we call DADA (Divisive
      Amplicon Denoising Algorithm). Without training data, DADA infers both the sample
      genotypes and error parameters that produced a metagenome data set. We
      demonstrate performance on control data sequenced on Roche's 454 platform, and
      compare the results to the most accurate denoising software currently available,
      AmpliconNoise. CONCLUSIONS: DADA is more accurate and over an order of magnitude
      faster than AmpliconNoise. It eliminates the need for training data to establish
      error parameters, fully utilizes sequence-abundance information, and enables
      inclusion of context-dependent PCR error rates. It should be readily extensible
      to other sequencing platforms such as Illumina.

PMID- 23113968
TI  - Prepulse inhibition of auditory change-related cortical responses.
AB  - BACKGROUND: Prepulse inhibition (PPI) of the startle response is an important
      tool to investigate the biology of schizophrenia. PPI is usually observed by use
      of a startle reflex such as blinking following an intense sound. A similar
      phenomenon has not been reported for cortical responses. RESULTS: In 12 healthy
      subjects, change-related cortical activity in response to an abrupt increase of
      sound pressure by 5 dB above the background of 65 dB SPL (test stimulus) was
      measured using magnetoencephalography. The test stimulus evoked a clear cortical
      response peaking at around 130 ms (Change-N1m). In Experiment 1, effects of the
      intensity of a prepulse (0.5 ~ 5 dB) on the test response were examined using a
      paired stimulation paradigm. In Experiment 2, effects of the interval between the
      prepulse and test stimulus were examined using interstimulus intervals (ISIs) of
      50 ~ 350 ms. When the test stimulus was preceded by the prepulse, the Change-N1m
      was more strongly inhibited by a stronger prepulse (Experiment 1) and a shorter
      ISI prepulse (Experiment 2). In addition, the amplitude of the test Change-N1m
      correlated positively with both the amplitude of the prepulse-evoked response and
      the degree of inhibition, suggesting that subjects who are more sensitive to the
      auditory change are more strongly inhibited by the prepulse. CONCLUSIONS: Since
      Change-N1m is easy to measure and control, it would be a valuable tool to
      investigate mechanisms of sensory gating or the biology of certain mental
      diseases such as schizophrenia.

PMID- 23113970
TI  - The negative predictive value of ultrasound-guided 14-gauge core needle biopsy of
      breast masses: a validation study of 339 cases.
AB  - PURPOSE: To determine the negative predictive value of sonographically guided 14
      gauge core needle biopsy of breast masses, with detailed analysis of any false
      negative cases. MATERIALS AND METHODS: We reviewed 669 cases of sonographically
      guided 14-gauge core needle biopsies that had benign pathologic findings. Given a
      benign pathology on core biopsy, true-negatives had either benign pathology on
      surgical excision or at least 2 years of stable imaging and/or clinical follow
      up; false-negatives had malignant histology on surgical excision. RESULTS: Follow
      up was available for 339 breast lesions; 117 were confirmed to be benign via
      surgical excision, and 220 were stable after 2 years or more of imaging or
      clinical follow-up (mean follow-up time 33.1 months, range 24-64 months). The
      negative predictive value was determined to be 99.4%. There were 2 false-negative
      cases, giving a false-negative rate of 0.1%. There was no delay in diagnosis in
      either case because the radiologist noted discordance between imaging and core
      biopsy pathology, and recommended surgical excision despite the benign core
      biopsy pathology. CONCLUSIONS: Sonographically guided 14-gauge core needle biopsy
      provides a high negative predictive value in assessing breast lesions.
      Radiologic/pathologic correlation should be performed to avoid delay in the
      diagnosis of carcinoma.

PMID- 23113971
TI  - Characterization of Trichuris trichiura from humans and T. suis from pigs in
      China using internal transcribed spacers of nuclear ribosomal DNA.
AB  - Trichuris trichiura and Trichuris suis parasitize (at the adult stage) the caeca
      of humans and pigs, respectively, causing trichuriasis. Despite these parasites
      being of human and animal health significance, causing considerable socio
      economic losses globally, little is known of the molecular characteristics of T.
      trichiura and T. suis from China. In the present study, the entire first and
      second internal transcribed spacer (ITS-1 and ITS-2) regions of nuclear ribosomal
      DNA (rDNA) of T. trichiura and T. suis from China were amplified by polymerase
      chain reaction (PCR), the representative amplicons were cloned and sequenced, and
      sequence variation in the ITS rDNA was examined. The ITS rDNA sequences for the
      T. trichiura and T. suis samples were 1222-1267 bp and 1339-1353 bp in length,
      respectively. Sequence analysis revealed that the ITS-1, 5.8S and ITS-2 rDNAs of
      both whipworms were 600-627 bp and 655-661 bp, 154 bp, and 468-486 bp and 530-538
      bp in size, respectively. Sequence variation in ITS rDNA within and among T.
      trichiura and T. suis was examined. Excluding nucleotide variations in the simple
      sequence repeats, the intra-species sequence variation in the ITS-1 was 0.2-1.7%
      within T. trichiura, and 0-1.5% within T. suis. For ITS-2 rDNA, the intra-species
      sequence variation was 0-1.3% within T. trichiura and 0.2-1.7% within T. suis.
      The inter-species sequence differences between the two whipworms were 60.7-65.3%
      for ITS-1 and 59.3-61.5% for ITS-2. These results demonstrated that the ITS rDNA
      sequences provide additional genetic markers for the characterization and
      differentiation of the two whipworms. These data should be useful for studying
      the epidemiology and population genetics of T. trichiura and T. suis, as well as
      for the diagnosis of trichuriasis in humans and pigs. 

PMID- 23113972
TI  - Single-molecule localization super-resolution microscopy: deeper and faster.
AB  - For over a decade fluorescence microscopy has demonstrated the capacity to
      achieve single-molecule localization accuracies of a few nanometers, well below
      the ~ 200 nm lateral and ~ 500 nm axial resolution limit of conventional
      microscopy. Yet, only the recent development of new fluorescence labeling
      modalities, the increase in sensitivity of imaging hardware, and the creation of
      novel image analysis tools allow for the emergence of single-molecule-based super
      resolution imaging techniques. Novel methods such as photoactivated localization
      microscopy and stochastic optical reconstruction microscopy can typically reach a
      tenfold increase in resolution compared to standard microscopy methods. Their
      implementation is relatively easy only requiring minimal changes to a
      conventional wide-field or total internal reflection fluorescence microscope. The
      recent translation of these two methods into commercial imaging systems has made
      them further accessible to researchers in biology. However, these methods are
      still evolving rapidly toward imaging live samples with high temporal resolution
      and depth. In this review, we recall the roots of single-molecule localization
      microscopy, summarize major recent developments, and offer perspective on
      potential applications.

PMID- 23113974
TI  - Electro-kinetics of charged-sphere suspensions explored by integral low-angle
      super-heterodyne laser Doppler velocimetry.
AB  - We investigated the flow behaviour of colloidal charged-sphere suspensions using
      a newly designed integral low-angle super-heterodyne laser Doppler velocimetry
      instrument, which combines the advantages of several previous approaches. Sample
      conditions ranged from strong electrostatic interactions with pronounced short
      range order to individual particles with no spatial correlations. The obtained
      power spectra correspond to diffusion broadened velocity distributions across the
      complete sample cross section. The excellent performance of the instrument is
      highlighted in detail by the example of electro-kinetic flow of suspensions in a
      closed cell of a rectangular cross section. We demonstrate the excellent
      performance of our approach with the example of electro-phoretic-electro-osmotic
      experiments, showing that a comprehensive flow characterization becomes possible
      by analysing the measured electro-kinetic mobilities, the flow-profile, an
      effective diffusion coefficient and the integrated scattering density. We briefly
      discuss present limitations, possible extensions and interesting applications in
      other fields.

PMID- 23113973
TI  - The spatial distribution of known predictors of autism spectrum disorders impacts
      geographic variability in prevalence in central North Carolina.
AB  - BACKGROUND: The causes of autism spectrum disorders (ASD) remain largely unknown
      and widely debated; however, evidence increasingly points to the importance of
      environmental exposures. A growing number of studies use geographic variability
      in ASD prevalence or exposure patterns to investigate the association between
      environmental factors and ASD. However, differences in the geographic
      distribution of established risk and predictive factors for ASD, such as maternal
      education or age, can interfere with investigations of ASD etiology. We evaluated
      geographic variability in the prevalence of ASD in central North Carolina and the
      impact of spatial confounding by known risk and predictive factors. METHODS:
      Children meeting a standardized case definition for ASD at 8 years of age were
      identified through records-based surveillance for 8 counties biennially from 2002
      to 2008 (n=532). Vital records were used to identify the underlying cohort (15%
      random sample of children born in the same years as children with an ASD,
      n=11,034), and to obtain birth addresses. We used generalized additive models
      (GAMs) to estimate the prevalence of ASD across the region by smoothing latitude
      and longitude. GAMs, unlike methods used in previous spatial analyses of ASD,
      allow for extensive adjustment of individual-level risk factors (e.g. maternal
      age and education) when evaluating spatial variability of disease prevalence.
      RESULTS: Unadjusted maps revealed geographic variation in surveillance-recognized
      ASD. Children born in certain regions of the study area were up to 1.27 times as
      likely to be recognized as having ASD compared to children born in the study area
      as a whole (prevalence ratio (PR) range across the study area 0.57-1.27; global
      P=0.003). However, geographic gradients of ASD prevalence were attenuated after
      adjusting for spatial confounders (adjusted PR range 0.72-1.12 across the study
      area; global P=0.052). CONCLUSIONS: In these data, spatial variation of ASD in
      central NC can be explained largely by factors impacting diagnosis, such as
      maternal education, emphasizing the importance of adjusting for differences in
      the geographic distribution of known individual-level predictors in spatial
      analyses of ASD. These results underscore the critical importance of accounting
      for such factors in studies of environmental exposures that vary across regions.

PMID- 23113975
TI  - Theoretical luminescence spectra in p-type superlattices based on InGaAsN.
AB  - In this work, we present a theoretical photoluminescence (PL) for p-doped
      GaAs/InGaAsN nanostructures arrays. We apply a self-consistent k->p-> method in
      the framework of the effective mass theory. Solving a full 8 * 8 Kane's
      Hamiltonian, generalized to treat different materials in conjunction with the
      Poisson equation, we calculate the optical properties of these systems. The
      trends in the calculated PL spectra, due to many-body effects within the quasi
      two-dimensional hole gas, are analyzed as a function of the acceptor doping
      concentration and the well width. Effects of temperature in the PL spectra are
      also investigated. This is the first attempt to show theoretical luminescence
      spectra for GaAs/InGaAsN nanostructures and can be used as a guide for the design
      of nanostructured devices such as optoelectronic devices, solar cells, and
      others.

PMID- 23113976
TI  - The measurement of 25-hydroxy vitamin D - an analytical challenge.

PMID- 23113977
TI  - 25-Hydroxyvitamin D testing: challenging the performance of current automated
      immunoassays.
AB  - BACKGROUND: Clinical laboratories require accurate and precise 25-hydroxyvitamin
      D (25-OHD) immunoassays to allow comparison of patient results with published
      decision limits. However, some variation in performance has been found with the
      previous generation of automated 25-OHD immunoassays. This study assessed the
      performance of four recently released automated 25-OHD immunoassays against a
      liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay. METHODS: A total
      of 983 samples from apparently healthy adults, plus 253 samples chosen to
      challenge the performance of the assays, were analyzed by the latest generation
      of immunoassays from Abbott, DiaSorin, Roche and Siemens. LC-MS/MS analysis was
      performed on a random subset of 264 samples. The precision of the immunoassays
      was assessed over 5 days with samples ranging between 3.0 and 370 nmol/L in
      concentration. RESULTS: Immunoassays showed significant differences in precision
      at 25-OHD concentrations of 3.0-86.5 nmol/L but all showed acceptable precision
      at higher concentrations. The DiaSorin assay agreed with LC-MS/MS across the
      measuring range of samples tested (7.7-425 nmol/L). The other assays showed
      generally good performance, but had some limitations when their performance was
      challenged with samples with low and high 25-OHD concentrations, heterophilic
      antibodies or high 25-OHD(2) concentrations. The C3-epimer of 25-OHD was
      identified in 40.4% of healthy adults tested and was a source of analytical
      variance in immunoassays. CONCLUSIONS: The latest generation of 25-OHD
      immunoassays has improved performance compared to previous assays. However, some
      immunoassays can still give discrepant results and this is most apparent when
      immunoassays are evaluated with a range of samples that challenge their
      analytical performance.

PMID- 23113978
TI  - The new Roche Vitamin D Total assay: fit for its purpose?
AB  - BACKGROUND: Measurement of serum 25-hydroxyvitamin D [25(OH)D] is used to assess
      vitamin D status. We evaluated the analytical performance of a new automated
      assay, Elecsys Vitamin D Total (Roche Diagnostics, Mannheim, Germany), based on
      competitive protein binding. METHODS: The Elecsys assay was tested for
      imprecision, linearity and functional sensitivity at three test-sites and
      compared to a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, a
      high-performance liquid chromatography (HPLC) method and the Liaison 25(OH)
      Vitamin D Total immunoassay (Diasorin). RESULTS: Imprecision testing with human
      serum specimens showed within-run CVs of <=6% and between-run CVs of <=8%. The
      assay was linear from 33 up to at least 111 nmol/L and showed equivalent 25(OH)D
      levels for matched serum and heparinized plasma samples. The assay correlated
      reasonable to well with LC-MS/MS (r=0.93; y=1.07x-5.04 nmol/L), HPLC (r=0.91,
      y=0.90x+3.03 nmol/L) and the Liaison assay (r=0.86, y=1.19x+2.80 nmol/L). Some of
      the samples showed large between-method differences. CONCLUSIONS: The new Elecsys
      assay fulfilled present analytical performance requirements and showed close
      agreement to other well-established methods for 25(OH)D analysis, making it fit
      for routine assessment of vitamin D status.

PMID- 23113979
TI  - Variational Bayes procedure for effective classification of tumor type with
      microarray gene expression data.
AB  - Recently, microarrays that can simultaneously measure the expression levels of
      thousands of genes have become a valuable tool for classifying tumors. For such
      classification, where the sample size is usually much smaller than the number of
      genes, it is essential to construct properly sparse models for accurately
      predicting tumor types to avoid over-fitting. Bayesian shrinkage estimation is
      considered a suitable method for providing such sparse models, effectively
      shrinking estimates of the effects for many irrelevant genes to zero while
      maintaining those of a small number of relevant genes at significant magnitudes.
      However, Bayesian analysis usually requires time-consuming computational
      techniques such as computationally intensive MCMC iterations. This paper
      describes a computationally effective method of Bayesian shrinkage regression
      (BSR) incorporating multiple hierarchical structures for constructing a
      classification model for tumor types using microarray gene expression data. We
      use a variational approximation method which provides simple approximations of
      posterior distributions of parameters to reduce computational burden in the
      Bayesian estimation. This computationally efficient BSR procedure yields a
      properly sparse model for accurately and rapidly classifying tumor samples. The
      accuracy of tumor classification is shown to be at least equivalent to that of
      other methods such as support vector machine and partial least squares using
      simulated and actual gene expression data sets.

PMID- 23113980
TI  - A novel algorithm for simultaneous SNP selection in high-dimensional genome-wide
      association studies.
AB  - BACKGROUND: Identification of causal SNPs in most genome wide association studies
      relies on approaches that consider each SNP individually. However, there is a
      strong correlation structure among SNPs that needs to be taken into account.
      Hence, increasingly modern computationally expensive regression methods are
      employed for SNP selection that consider all markers simultaneously and thus
      incorporate dependencies among SNPs. RESULTS: We develop a novel multivariate
      algorithm for large scale SNP selection using CAR score regression, a promising
      new approach for prioritizing biomarkers. Specifically, we propose a
      computationally efficient procedure for shrinkage estimation of CAR scores from
      high-dimensional data. Subsequently, we conduct a comprehensive comparison study
      including five advanced regression approaches (boosting, lasso, NEG, MCP, and CAR
      score) and a univariate approach (marginal correlation) to determine the
      effectiveness in finding true causal SNPs. CONCLUSIONS: Simultaneous SNP
      selection is a challenging task. We demonstrate that our CAR score-based
      algorithm consistently outperforms all competing approaches, both uni- and
      multivariate, in terms of correctly recovered causal SNPs and SNP ranking. An R
      package implementing the approach as well as R code to reproduce the complete
      study presented here is available from http://strimmerlab.org/software/care/.

PMID- 23113981
TI  - Validation of the Dutch version of the DN4 diagnostic questionnaire for
      neuropathic pain.
AB  - Difficulties in diagnosing neuropathic pain in routine clinical practice support
      the need for validated and easy-to-use diagnostic tools. The DN4 neuropathic pain
      diagnostic questionnaire aims to discriminate neuropathic pain from nociceptive
      pain, but needs clinical validation. A total of 269 patients with chronic pain in
      three pain clinics were included in the study of which 248 had analyzable data.
      The mean duration of pain was 4.9 years. The most frequent etiologies were
      posttraumatic (36%), (pseudo) radicular (14%), and mechanical back pain (12%).
      The mean intensity of pain at visit was 5.6 on a 0-10 scale. Hundred and ninety
      six of 248 patients had an identical pain diagnosis from both physicians: 85 had
      neuropathic pain, 57 had nociceptive pain, and 54 had mixed pain. Among patients
      with identical diagnoses of neuropathic or nociceptive pain, using a receiver
      operating characteristic curve analysis, the area under the curve (AUC) was 0.81
      for the DN4 7-item and 0.82 for the 10-item version. A cutoff point of 5/10 for
      the full questionnaire resulted in a sensitivity of 75% and a specificity of 79%,
      while a cutoff point of 4/7 for the partial questionnaire resulted in a
      sensitivity of 74% and a specificity of 79%. The items "brushing," "painful
      cold," and "numbness" were most discriminating. The DN4 is an easy-to-use
      screening tool that is reliable for discriminating between neuropathic and
      nociceptive pain conditions in daily practice. Item-specific scores provide
      important information in addition to the total score.

PMID- 23113983
TI  - Electrokinetics on superhydrophobic surfaces.
AB  - On a superhydrophobic surface a liquid is exposed to a large air-water interface.
      The reduced wall friction is expected to cause a higher electro-osmotic mobility.
      On the other hand, the low charge density of a superhydrophobic surface reduces
      the electro-osmotic mobility. Due to a lack of experimental data it has not been
      clear so far whether the reduced wall friction or the reduced charge density
      dominate the electrokinetic mobilities. To separate the relative contributions of
      electrophoresis and electro-osmosis, the mobilities of colloids on a negatively
      charged hydrophilic, a superhydrophobic (Cassie) and a partially hydrophilized
      superhydrophobic (Cassie composite) coating were measured. To vary the charge
      density as well as its sign with respect to those of the colloids the partially
      hydrophilized surfaces were coated with polyelectrolytes. We analyzed the
      electrokinetic mobilities of negatively charged polystyrene colloids dispersed in
      aqueous medium on porous hydrophilic and superhydrophobic surfaces by confocal
      laser scanning electron microscopy. In all cases, the external electric field was
      parallel to the surface. The total electrokinetic mobilities on the
      superhydrophobic (Cassie) and negatively charged partially hydrophilized (Cassie
      composite) surfaces were similar, showing that electro-osmosis is small compared
      to electrophoresis. The positively charged Cassie composite surfaces tend to
      'trap' the colloids due to attracting electrostatic interactions and rough
      morphology, reducing the mobility. Thus, either the charge density of the
      coatings in the Cassie composite state or its slip length is too low to enhance
      electro-osmosis.

PMID- 23113982
TI  - Expression of flavonoid 3'-hydroxylase is controlled by P1, the regulator of 3
      deoxyflavonoid biosynthesis in maize.
AB  - BACKGROUND: The maize (Zea mays) red aleurone1 (pr1) encodes a CYP450-dependent
      flavonoid 3'-hydroxylase (ZmF3'H1) required for the biosynthesis of purple and
      red anthocyanin pigments. We previously showed that Zmf3'h1 is regulated by C1
      (Colorless1) and R1 (Red1) transcription factors. The current study demonstrates
      that, in addition to its role in anthocyanin biosynthesis, the Zmf3'h1 gene also
      participates in the biosynthesis of 3-deoxyflavonoids and phlobaphenes that
      accumulate in maize pericarps, cob glumes, and silks. Biosynthesis of 3
      deoxyflavonoids is regulated by P1 (Pericarp color1) and is independent from the
      action of C1 and R1 transcription factors. RESULTS: In maize, apiforol and
      luteoforol are the precursors of condensed phlobaphenes. Maize lines with
      functional alleles of pr1 and p1 (Pr1;P1) accumulate luteoforol, while null pr1
      lines with a functional or non-functional p1 allele (pr1;P1 or pr1;p1) accumulate
      apiforol. Apiforol lacks a hydroxyl group at the 3'-position of the flavylium B
      ring, while luteoforol has this hydroxyl group. Our biochemical analysis of
      accumulated compounds in different pr1 genotypes showed that the pr1 encoded
      ZmF3'H1 has a role in the conversion of mono-hydroxylated to bi-hydroxylated
      compounds in the B-ring. Steady state RNA analyses demonstrated that Zmf3'h1 mRNA
      accumulation requires a functional p1 allele. Using a combination of EMSA and
      ChIP experiments, we established that the Zmf3'h1 gene is a direct target of P1.
      Highlighting the significance of the Zmf3'h1 gene for resistance against biotic
      stress, we also show here that the p1 controlled 3-deoxyanthocyanidin and C
      glycosyl flavone (maysin) defence compounds accumulate at significantly higher
      levels in Pr1 silks as compared to pr1 silks. By virtue of increased maysin
      synthesis in Pr1 plants, corn ear worm larvae fed on Pr1; P1 silks showed slower
      growth as compared to pr1; P1 silks. CONCLUSIONS: Our results show that the
      Zmf3'h1 gene participates in the biosynthesis of phlobaphenes and agronomically
      important 3-deoxyflavonoid compounds under the regulatory control of P1.

PMID- 23113985
TI  - [Antiangiogenic agents: current limits in thoracic oncology].
AB  - Antiangiogenic agents appear as major therapeutic options in renal, colorectal
      and breast cancer. Their part in thoracic oncology is still limited today except
      for bevacizumab. We review the current limits of antiangiogenic agents in terms
      of efficacy, activity, tolerance and therapeutic strategies. Problems about
      predictive biomarkers and cost-effectiveness of antiangiogenic agents in thoracic
      oncology are also mentioned.

PMID- 23113984
TI  - The birth of the Epitranscriptome: deciphering the function of RNA modifications.
AB  - Recent studies have found methyl-6-adenosine in thousands of mammalian genes, and
      this modification is most pronounced near the beginning of the 3' UTR. We present
      a perspective on current work and new single-molecule sequencing methods for
      detecting RNA base modifications. 

PMID- 23113986
TI  - Time trends in coroners' use of different verdicts for possible suicides and
      their impact on officially reported incidence of suicide in England: 1990-2005.
AB  - BACKGROUND: Official suicide statistics for England are based on deaths given
      suicide verdicts and most cases given an open verdict following a coroner's
      inquest. Previous research indicates that some deaths given accidental verdicts
      are considered to be suicides by clinicians. Changes in coroners' use of
      different verdicts may bias suicide trend estimates. We investigated whether
      suicide trends may be over- or underestimated when they are based on deaths given
      suicide and open verdicts. Method Possible suicides assessed by 12 English
      coroners in 1990/91, 1998 and 2005 and assigned open, accident/misadventure or
      narrative verdicts were rated by three experienced suicide researchers according
      to the likelihood that they were suicides. Details of all suicide verdicts given
      by these coroners were also recorded. RESULTS: In 1990/91, 72.0% of researcher
      defined suicides received a suicide verdict from the coroner, this decreased to
      65.4% in 2005 (p trend < 0.01); equivalent figures for combined suicide and open
      verdicts were 95.4% (1990/91) and 86.7% (2005). Researcher-defined suicides with
      a verdict of accident/misadventure doubled over that period, from 4.6% to 9.1% (p
      < 0.01). Narrative verdict cases rose from zero in 1990/91 to 25 in 2005 (4.2% of
      researcher-defined suicides that year). In 1998 and 2005, 50.0% of the medicine
      poisoning deaths given accidental/misadventure verdicts were rated as suicide by
      the researchers. CONCLUSIONS: Between 1990/91 and 2005, the proportion of
      researcher-defined suicides given a suicide verdict by coroners decreased,
      largely due to an increased use of accident/misadventure verdicts, particularly
      for deaths involving poisoning. Consideration should be given to the inclusion of
      'accidental' deaths by poisoning with medicines in the statistics available for
      monitoring suicides rates.

PMID- 23113987
TI  - Chronologically matched toenail-Hg to hair-Hg ratio: temporal analysis within the
      Japanese community (U.S.).
AB  - BACKGROUND: Toenail-Hg levels are being used as a marker of methylmercury (MeHg)
      exposure in efforts to associate exposure with effects such as cardiovascular
      disease. There is a need to correlate this marker with more established
      biomarkers that presently underlie existing dose-response relationships in order
      to compare these relationships across studies. METHODS: As part of the Arsenic
      Mercury Intake Biometric Study, toenail clippings were collected at three time
      points over a period of one year amongst females from within the population of
      Japanese living near Puget Sound in Washington State (US). Variability in
      temporal intra-individual toenail-Hg levels was examined and chronologically
      matched hair and toenail samples were compared to more accurately define the
      toxicokinetic variability of Hg levels observed between the two compartments.
      RESULTS: Mean toenail-Hg values (n=43) for the 1st, 2nd and 3rd visits were 0.60,
      0.60 and 0.56 ng/mg. Correlations were as follows: r=0.92 between 1st and 2nd
      clinic visits, r=0.75 between 1st and 3rd visits and r=0.87 between 2nd and 3rd
      visits. With few exceptions, toenail-Hg values from any visit were within 50-150%
      of the individual's mean toenail-Hg level. Nearly all participants had less than
      a two-fold change in toenail-Hg levels across the study period. A regression
      model of the relationship between toenail-Hg and hair-Hg (n = 41) levels
      representing the same time period of exposure, gave a slope (Hg ng/mg) of 2.79
      for hair relative to toenail (r=0.954). CONCLUSIONS: A chronologically matched
      hair-Hg to toenail-Hg ratio has been identified within a population that consumes
      fish regularly and in quantity. Intra-individual variation in toenail-Hg levels
      was less than two-fold and may represent dietary-based fluctuations in body
      burden for individuals consuming various fish species with different contaminant
      levels. The chronologically matched ratio will be useful for relating MeHg
      exposure and dose-response derived from toenail-Hg measurements to those derived
      from hair-Hg measurements in other studies, and may be useful in future
      investigations as an indicator of stable MeHg body burden within a population.

PMID- 23113988
TI  - Occupational therapy predischarge home visits for patients with a stroke (HOVIS):
      results of a feasibility randomized controlled trial.
AB  - OBJECTIVE: To assess the feasibility of conducting a randomized controlled trial
      of occupational therapy predischarge home visits for people after stroke. DESIGN:
      Randomized controlled trial and cohort study. We randomized eligible patients for
      whom there was clinical uncertainty about the need to conduct a home visit to a
      randomized controlled trial; patients for whom a visit was judged 'essential'
      were enrolled into a cohort study. SETTING: Stroke rehabilitation unit of
      teaching hospital. PARTICIPANTS: One hundred and twenty-six participants
      hospitalized following recent stroke. INTERVENTIONS: Predischarge home visit or
      structured, hospital-based interview. MAIN OUTCOME MEASURES: The primary
      objective was to collect information on the feasibility of a randomized
      controlled trial, including eligibility, control intervention and outcome
      assessments. The primary outcome measure was the Nottingham Extended Activities
      of Daily Living Scale at one month after discharge from hospital. Secondary
      outcomes included mood, quality of life and costs at one week and one month
      following discharge. RESULTS: Ninety-three people were allocated to the
      randomized controlled trial; 47 were randomized to intervention and 46 to
      control. Thirty-three were enrolled into the cohort study. More people were
      allocated to the randomized controlled trial as the study progressed. One hundred
      and thirteen people (90%) received the proposed intervention, although there was
      a need for stricter protocol adherence. Follow-up was good: at one month 114
      (90%) were assessed. There were no significant differences between the groups in
      the randomized controlled trial for the primary outcome measure at one month. The
      average cost of a home visit was L208. CONCLUSION: A trial is feasible and
      warranted given the resource implications of predischarge occupational therapy
      home visits.

PMID- 23113989
TI  - Long-term effects of new progressive group balance training for elderly people
      with increased risk of falling - a randomized controlled trial.
AB  - OBJECTIVE: To evaluate the long-term effects of a progressive and specific
      balance group-based program in healthy elderly individuals with increased risk of
      falling. DESIGN: Follow-up of a randomized controlled trial at nine and 15 months
      on a population that has previously been described at three months. SETTING: The
      study was conducted in Stockholm, Sweden. SUBJECTS: 59 community-dwelling elderly
      (age 67-93 years), recruited by advertisement, were randomly allocated to
      training or to serve as controls. INTERVENTION: Group balance training three
      times per week during 12 weeks with a 15 month follow-up time. MAIN MEASURES:
      Participants were assessed at baseline, three, nine, and 15 months thereafter for
      gait function (preferred and fast walking), rapid step execution (single and dual
      task), fear of falling, and likelihood of depression. RESULTS: Fast gait speed (p
      = 0.004), dual task step execution (p = 0.006) and fear of falling (p = 0.001)
      were still improved in the training group at nine months follow-up. Only self
      perceived fear of falling remained significantly improved (p = 0.012) at 15
      months follow-up. Although fast gait speed had decreased to baseline level in the
      training group (1.49 m/s) it remained significantly higher than in the control
      group (1.37 m/s) at the end of the study, a difference between the groups that
      was not seen at baseline. CONCLUSION: This training program provided important
      positive short and long-term benefits to gait, balance function, and fear of
      falling.

PMID- 23113990
TI  - Dynamic changes in the secondary structure of ECE-1 and XCE account for their
      different substrate specificities.
AB  - BACKGROUND: X-converting enzyme (XCE) involved in nervous control of respiration,
      is a member of the M13 family of zinc peptidases, for which no natural substrate
      has been identified yet. In contrast, it's well characterized homologue
      endothelin-converting enzyme-1 (ECE-1) showed broad substrate specificity and
      acts as endopeptidase as well as dipeptidase. To explore the structural
      differences between XCE and ECE-1, homology model of XCE was built using the
      complex structure of ECE-1 with phosphoramidon (pdb-id: 3DWB) as template.
      Phosphoramidon was docked into the binding site of XCE whereas phosphate oxygen
      of the inhibitor was used as water molecule to design the apo forms of both
      enzymes. Molecular dynamics simulation of both enzymes was performed to analyze
      the dynamic nature of their active site residues in the absence and presence of
      the inhibitor. RESULTS: Homology model of XCE explained the role of non-conserved
      residues of its S2' subsite. Molecular dynamics (MD) simulations identified the
      flexible transitions of F149/I150, N566/N571, W714/W719, and R145/R723 residues
      of ECE-1/XCE for the strong binding of the inhibitor. Secondary structure
      calculations using DSSP method reveals the folding of R145/R723 residue of ECE
      1/XCE into beta-sheet structure while unfolding of the S2' subsite residues in
      aECE-1 and sustained compact folding of that of aXCE. The results evaluated are
      in good agreement with available experimental data, thus providing detailed
      molecular models which can explain the structural and specificities differences
      between both zinc peptidases. CONCLUSIONS: Secondary structure changes of both
      enzymes during the simulation time revealed the importance of beta-sheet
      structure of R145/R723 for its binding with the terminal carboxylate group of the
      inhibitor. Unfolding of the alpha-helix comprising the S2' subsite residues in
      aECE-1 correlate well with its endopeptidase activity while their compact folding
      in aXCE may account for the inactivity of the enzyme towards large C-terminal
      containing substrates.

PMID- 23113991
TI  - Nanomechanical characterization of chemical interaction between gold
      nanoparticles and chemical functional groups.
AB  - We report on how to quantify the binding affinity between a nanoparticle and
      chemical functional group using various experimental methods such as cantilever
      assay, PeakForce quantitative nanomechanical property mapping, and lateral force
      microscopy. For the immobilization of Au nanoparticles (AuNPs) onto a microscale
      silicon substrate, we have considered two different chemical functional molecules
      of amine and catecholamine (here, dopamine was used). It is found that
      catecholamine-modified surface is more effective for the functionalization of
      AuNPs onto the surface than the amine-modified surface, which has been shown from
      our various experiments. The dimensionless parameter (i.e., ratio of binding
      affinity) introduced in this work from such experiments is useful in
      quantitatively depicting such binding affinity, indicating that the binding
      affinity and stability between AuNPs and catecholamine is approximately 1.5 times
      stronger than that between amine and AuNPs. Our study sheds light on the
      experiment-based quantitative characterization of the binding affinity between
      nanomaterial and chemical groups, which will eventually provide an insight into
      how to effectively design the functional material using chemical groups.

PMID- 23113992
TI  - [Stereotactic radiotherapy and radiofrequency ablation for early-stage lung
      cancer].
AB  - Surgery is the standard treatment of early-stage non-small cell lung cancer
      (NSCLC). However, all patients do not undergo radical resection because of the
      very frequent co-morbidities occurring in smokers. Recently, new therapeutic
      options have emerged for limited-size (less than 4 cm) NSCLC tumors. Stereotactic
      radiotherapy consists of the use of multiple radiation micro-beams, allowing high
      doses of radiation to be delivered to the tumor in a small number of fractions.
      Radiofrequency ablation delivers high frequency electromagnetic waves through a
      needle-like probe, that produces ionic agitation, increase of the temperature in
      the tumor tissue, and ultimately leads to coagulation necrosis of the tumor.
      Several studies have been reported, that show the efficacy of these treatment
      modalities to control stage I/II NSCLC in medically inoperable patients. Local
      control rates are consistently reported to be above 90 %. Stereotactic radiation
      therapy and radiofrequency ablation are now being evaluated prospectively;
      namely, stereotactic radiotherapy is being compared to surgery in operable
      patients in several randomized trials. Overall, from a technical concept to the
      availability of specific treatment devices and the publication of clinical
      results, stereotactic radiotherapy and radiofrequency ablation are paradigms of
      implementation in thoracic oncology.

PMID- 23113993
TI  - Numerical electrokinetics.
AB  - A new lattice method is presented in order to efficiently solve the
      electrokinetic equations, which describe the structure and dynamics of the charge
      cloud and the flow field surrounding a single charged colloidal sphere, or a
      fixed array of such objects. We focus on calculating the electrophoretic mobility
      in the limit of small driving field, and systematically linearize the equations
      with respect to the latter. This gives rise to several subproblems, each of which
      is solved by a specialized numerical algorithm. For the total problem we combine
      these solvers in an iterative procedure. Applying this method, we study the
      effect of the screening mechanism (salt screening versus counterion screening) on
      the electrophoretic mobility, and find a weak non-trivial dependence, as expected
      from scaling theory. Furthermore, we find that the orientation of the charge
      cloud (i.e. its dipole moment) depends on the value of the colloid charge, as a
      result of a competition between electrostatic and hydrodynamic effects.

PMID- 23113994
TI  - Hypothesis-driven genomics pays off.

PMID- 23113996
TI  - Compensatory role of saccule in deaf children and adults: novel hypotheses.
AB  - The aim of the present study is to measure sound sensitivity of the saccule for
      low frequencies in a population of both young and adult prelingual deaf patients
      using cervical Vestibular Evoked Myogenic Potentials (cVEMPs) and to correlate
      the findings obtained with the phonological features. The sensitivity of the
      saccule to sound stimuli is well known in previous studies. The functional role
      of the human saccule in responding to sound stimuli is still unclear. The study
      was conducted on a control population of young and adults with normal hearing.
      The outcomes showed that the amplitude of myogenic vestibular evoked potentials
      resulted the most significant parameter, indicating the degree of saccular
      response. We found in the group of deaf adults that the saccule retained an
      unaltered responsiveness to sound stimuli, without suffering the age-related
      functional decrease as demonstrated in normal hearing patients. We assumed that
      the high saccular response in deaf patients is determined by a constant
      somatosensory stimulation (rehabilitation) of the saccule, represented by the
      phonetic training. We correlated the phonetic features typical of the deaf with
      the sensitivity of the saccule to low frequencies. Such sensitivity makes this
      organ the ending point of the phonetic information (perception) but also the
      starting point of its regulation (production). Our experience demonstrates the
      phonetic role of saccule in the regulation of the human voice and provides the
      basis for further development of this topic. Thus we strongly believe that in the
      deaf the saccule plays a compensatory role. The high response of the saccule
      allows phonemic self-regulation, compensating the low/absent tone-verbal
      feedback. The saccule would come rightfully to be the accessory inner ear in deaf
      patients. We recommend the cVEMPs in the audio-phonological assessment before
      starting the speech therapy or during treatment to assess the degree of
      responsiveness of the saccule. The resulting data would give an extremely useful
      information that could be ignored by the pure tone audiometry. The presence of
      the cVEMPs in the deaf patient may improve the expectation of the performance of
      speech therapy.

PMID- 23113995
TI  - Barriers to pandemic influenza vaccination and uptake of seasonal influenza
      vaccine in the post-pandemic season in Germany.
AB  - BACKGROUND: In Germany, annual vaccination against seasonal influenza is
      recommended for certain target groups (e.g. persons aged >=60 years, chronically
      ill persons, healthcare workers (HCW)). In season 2009/10, vaccination against
      pandemic influenza A(H1N1)pdm09, which was controversially discussed in the
      public, was recommended for the whole population. The objectives of this study
      were to assess vaccination coverage for seasonal (seasons 2008/09-2010/11) and
      pandemic influenza (season 2009/10), to identify predictors of and barriers to
      pandemic vaccine uptake and whether the controversial discussions on pandemic
      vaccination has had a negative impact on seasonal influenza vaccine uptake in
      Germany. METHODS: We analysed data from the 'German Health Update' (GEDA10)
      telephone survey (n=22,050) and a smaller GEDA10-follow-up survey (n=2,493),
      which were both representative of the general population aged >=18 years living
      in Germany. RESULTS: Overall only 8.8% of the adult population in Germany
      received a vaccination against pandemic influenza. High socioeconomic status,
      having received a seasonal influenza shot in the previous season, and belonging
      to a target group for seasonal influenza vaccination were independently
      associated with the uptake of pandemic vaccines. The main reasons for not
      receiving a pandemic vaccination were 'fear of side effects' and the opinion that
      'vaccination was not necessary'. Seasonal influenza vaccine uptake in the pre
      pandemic season 2008/09 was 52.8% among persons aged >=60 years; 30.5% among HCW,
      and 43.3% among chronically ill persons. A decrease in vaccination coverage was
      observed across all target groups in the first post-pandemic season 2010/11
      (50.6%, 25.8%, and 41.0% vaccination coverage, respectively). CONCLUSIONS:
      Seasonal influenza vaccination coverage in Germany remains in all target groups
      below 75%, which is a declared goal of the European Union. Our results suggest
      that controversial public discussions about safety and the benefits of pandemic
      influenza vaccination may have contributed to both a very low uptake of pandemic
      vaccines and a decreased uptake of seasonal influenza vaccines in the first post
      pandemic season. In the upcoming years, the uptake of seasonal influenza vaccines
      should be carefully monitored in all target groups to identify if this trend
      continues and to guide public health authorities in developing more effective
      vaccination and communication strategies for seasonal influenza vaccination.

PMID- 23113998
TI  - Doing quality: an agenda for GP leadership to improve patient care.

PMID- 23113997
TI  - Flaxseed oil and alpha-lipoic acid combination reduces atherosclerosis risk
      factors in rats fed a high-fat diet.
AB  - BACKGROUND: Atherosclerosis is a major manifestation of the pathophysiology
      underlying cardiovascular disease. Flaxseed oil (FO) and alpha-lipoic acid (LA)
      have been reported to exert potential benefit to cardiovascular system. This
      study tried to assess the effect of supplement of FO and LA combination on the
      atherosclerosis risk factors in rats fed a high-fat diet. METHODS: LA was
      dissolved in flaxseed oil to a final concentration of 8 g/kg (FO+LA) when used.
      The rodent diet contained 20% fat. One-fifth of the fat was soybean oil and the
      others were lard (HFD group), or 75% lard and 25% FO+LA (L-FO+LA group), or 50%
      lard and 50% FO+LA (M-FO+LA group), or FO+LA (H-FO+LA group). Animals were fed
      for 10 weeks and then killed for blood collection. RESULTS: Supplement of FO and
      LA combination significantly enhanced plasma antioxidant defense capacities, as
      evaluated by the marked increase in the activities of SOD, CAT and GPx as well as
      the level of GSH, and the significant reduction in lipid peroxidation.
      Simultaneous intake of FO and LA also reduced plasma TG, TC and LDL-C contents
      and elevated the ratio of HDL-C/LDL-C. Besides, in parallel with the increase of
      FO and LA combination, plasma IL-6 and CRP levels were remarkably reduced.
      CONCLUSION: Supplement of FO and LA combination may contribute to prevent
      atherogenesis by improving plasma oxidative stress, lipid profile and
      inflammation.

PMID- 23113999
TI  - Healthcare in Asia: a perspective from primary care at the gateway to a
      continent.
AB  - Malaysia has achieved reasonable health outcomes even though the country spends a
      modest amount of Gross Domestic Product on healthcare. However, the country is
      now experiencing a rising incidence of both infectious diseases and chronic
      lifestyle conditions that reflect growing wealth  in a vibrant and successful
      economy. With an eye on an ageing population, reform of the health sector is a
      government priority. As in other many parts of the world, general practitioners
      are the first healthcare professional consulted by patients. The Malaysian health
      system is served by public  and private care providers. The integration of the
      two sectors is a key target for reform. However, the future health of the nation
      will depend on leadership in the primary care sector. This leadership will need
      to be informed by research to integrate care providers, empower patients, bridge 
      cultural gaps and ensure equitable access to scarce health resources.

PMID- 23114000
TI  - Impact of a priority-setting consultation on doctor-patient agreement after a
      geriatric assessment: cluster randomised controlled trial in German general
      practices.
AB  - BACKGROUND: General Practitioners (GPs) often have to simultaneously tackle
      multiple health problems of older patients. A patient-centred process that
      engages the patient in setting health priorities for treatment is needed. We
      investigated whether a structured priority-setting consultation reconciles the
      often-differing doctor-patient views on the importance of problems. DESIGN:
      Cluster randomised controlled trial with 40 GPs and their 317 consecutively
      recruited older patients. PROCEDURE: Following a geriatric assessment, patients
      and doctors independently rated the importance of each uncovered problem. GPs
      then selected priorities with their patients in a consultation. Trained
      intervention GPs held a structured consultation and utilised the list of
      uncovered patient problems with their importance ratings to agree priorities.
      Untrained control GPs only used the patient's problem list without importance
      ratings. MAIN OUTCOME: Doctor-patient agreement on independent importance ratings
      two weeks after the priority-setting consultation. ANALYSIS: Weighted kappa
      (kappaw) and multilevel logistic regression model. RESULTS: Intervention GPs and
      their patients determined mutual priorities for 20% of individual problems. In
      this process, GPs often succeeded in convincing their patients of the importance
      of vaccinations, lifestyle and cognitive issues. Likewise, patients convinced
      their GPs to prioritise their social and functional problems. Further treatment
      plans ensued in 84% of these priority areas. The regression model adjusting for
      clusters and baseline characteristics did not demonstrate significant differences
      in doctor-patient agreement on problems between groups a two weeks later.
      CONCLUSION: Differing views on the importance of health problems between GPs and
      older patients were not sustainably reconciled. The special consultation
      facilitated identification of priority problems for treatment despite differences
      in perceived importance of problems between patients and GPs. German clinical
      trials register drks 00000792.

PMID- 23114001
TI  - Clinical practice and variation in care for childhood obesity at seven clinics in
      California.
AB  - BACKGROUND: The Healthy Eating Active Living TeleHealth Community of Practice is
      a virtual quality-improvement learning network of seven rural clinics in
      California. The goal of this network is to improve childhood obesity prevention
      and management practices at participating  clinics. AIM: Our objective is to
      describe clinical practices regarding weight assessment and nutrition and
      physical activity counselling at participating clinics before implementation of
      the quality improvement intervention. METHODS: Participants were 2-11 year old 
      children seen for well-child care in 2010. Telephone surveys of English and
      Spanish-speaking parents were conducted within three days of their child's well
      child visit to determine the content of counselling during the visit regarding
      nutrition and physical activity. Medical record reviews  were conducted to
      determine clinicians' assessment of weight status. FINDINGS: Twenty-seven
      clinicians conducted 144 well-child visits included in the study. Body mass index
      (BMI) was documented in 71% of medical records. Fewer than 10% of medical records
      had documentation of weight  category. Sixty-nine percent of parents received
      counselling on physical activity and 62% reported receiving counselling on fruit
      and vegetable intake. Parents were counselled less frequently on breakfast
      intake, sweetened beverages, television and family meals. Parents of
      overweight/obese  children did not receive more counselling than parents of
      children with a healthy BMI. Clinician-level effects accounted for moderately
      large amount of variation in counselling, but accounted for smaller variation in
      documentation of BMI and weight category. There was high between-clinic variation
      in documentation practices, with 54% of the total variance for documentation
      attributable to clinic-level effects. CONCLUSIONS: Rural clinicians, like those
      elsewhere, do not uniformly assess BMI percentile or counsel families on
      behavioural risk factors for paediatric obesity. There  exists considerable
      clinician-level variation in counselling practices and clinic-site level
      correlation in documentation practices related to BMI percentile and weight
      category.

PMID- 23114002
TI  - Improving services for back pain: putting the patient at the centre of
      interprofessional education.
AB  - INTRODUCTION: Studies exploring the role of patients in interprofessional
      education (IPE) are found primarily in undergraduate programmes with few
      reporting on the postgraduate (continuing professional development) setting. This
      paper describes an interprofessional quality improvement  project around the
      management of back pain in a primary care setting where patients were part of the
      practice team. METHODS: Patients participated in eight half-day IPE workshops
      delivered to nine general practice teams in the UK. Educational content included
      knowledge about quality  improvement and evidence-based back pain knowledge, with
      teamwork, experiential and didactic learning approaches. On-site practice support
      from a quality improvement facilitator occurred between the workshops to
      strengthen practice-based learning. Forty-four practice staff and 11 patients 
      attended the workshops and the facilitated project meetings. Evaluation occurred
      through focus groups with practice teams (including patients) both before and
      after the workshops. These were recorded, transcribed and analysed by coding and
      the inductive development of themes. RESULTS: The context of managing back pain
      was particularly challenging. Focus group participants indicated that patient
      involvement was highly valued as it gave practitioners a greater understanding of
      the effects of back pain on their lives whilst permitting patients to hear the
      experiences of others  and to understand their own world better. Listening was
      important to patients' experiences of healthcare and practitioners' experiences
      of the workshops. Learning together emerged as particularly important and finally
      the challenge of finding time to learn together infiltrated the entire endeavour 
      and was a prominent concern. DISCUSSION: Patients sharing their experience of
      back pain appeared to be a particularly pivotal point in the learning for
      practice teams. Meaningful engagement with users in IPE was highly valued and
      provided a catalyst for behavioural change, where  professionals relinquished an
      unhelpful medical model in favour of an integrative biopsychosocial one.

PMID- 23114003
TI  - Physical activity and exercise counselling: a cross-sectional study of family
      practice patients in Estonia.
AB  - BACKGROUND: Low levels of physical activity are common in developed countries.
      Therefore, regular exercise counselling in family practice is potentially
      important. AIMS: To assess the physical activity of consecutive patients in
      family practice settings and to find  out whether patients seek advice from their
      family doctors (FDs) regarding physical activity. METHODS: The study group was
      made up of consecutive patients aged 18 to 75 years from five family practices
      across Estonia. Every patient completed a questionnaire to assess physical
      activity  and exercise counselling. The patient's level of physical activity in
      metabolic units per week (MET, min/week) was calculated on the basis of the
      International Physical Activity Questionnaire (IPAQ). Questions about counselling
      for physical activity and lifestyle were also included. RESULTS: The total number
      of patients was 239. According to the IPAQ, 47% of the patients showed high (MET
      >= 3001), 41% moderate (MET = 601-3000) and 12% low (MET leq 600) physical
      activity during the previous seven days. Higher physical activity was observed in
      patients living in rural  rather than urban areas (P = 0.025) and in patients who
      did not suffer from a chronic disease (P = 0.044). Twenty-three percent of
      participants reported having sought their FD's advice on physical activity and
      34% reported that they had received counselling for physical activity.
      CONCLUSIONS: Physical activity levels in consecutive family practice patients
      were high in Estonia: 88% of patients reported a moderate or high level of
      physical activity. In patients' opinions, FDs mostly counsel elderly and obese
      patients and those with chronic diseases. By contrast, the overall frequency  of
      counselling for physical activity was low.

PMID- 23114004
TI  - Management of chronic obstructive pulmonary disease in Swiss primary care: room
      for improvement.
AB  - BACKGROUND: Information on the quality of care for patients with chronic
      obstructive pulmonary disease (COPD) in Swiss primary care is limited. AIM: To
      identify gaps and quality improvement potential in COPD primary care in
      Switzerland. METHODS: Pooled analysis  of selected published data. Six
      international COPD guidelines (German, Swiss, United Kingdom, Canadian,
      Australian and New Zealand, and the global initiative on obstructive lung disease
      [GOLD] guidelines) were reviewed for care elements with a level of evidence rated
      II and higher in at least  three of the six guidelines. We compared published
      data on COPD management in Swiss primary care with these recommendations and with
      published international benchmarks. RESULTS: Nine elements fulfilled the criteria
      for evidence level II or higher in at least three of six COPD guidelines.  These
      were summarised in six key domains: diagnosis, smoking cessation counselling,
      influenza vaccination, pharmacological treatment, patient education and pulmonary
      rehabilitation (long-term oxygen and palliative care are not the focus of COPD
      primary care in Switzerland and outpatient exacerbation  management was
      subordinated to pharmacological treatment and education). Swiss primary care data
      revealed spirometric confirmation of diagnosis in 55% of patients, smoking
      cessation counselling in 50% and influenza vaccination in 66%. Inadequate
      prescription of inhaled corticosteroids (ICS)  was high at 38% in mild COPD and
      43% in moderate COPD. Referral for pulmonary rehabilitation, even for patients
      with severe COPD, was low at 19% and data on patient education were rare.
      Diagnosis, patient education and referral for pulmonary rehabilitation revealed
      the highest, and influenza  vaccination the lowest performance gap. CONCLUSION:
      Gaps between current care and recommended best practice exist in Swiss primary
      care COPD management. Promoting and implementing evidence-based frameworks for
      developing high quality care for patients with COPD are necessary.

PMID- 23114005
TI  - Patients' evaluations of family practice care and attributes of a good family
      physician.
AB  - OBJECTIVE: Patient evaluation of family practice care is the most direct
      assessment of quality of healthcare services provided. This study aimed to
      evaluate family practice care and to assess patient views on the attributes of a
      good family physician. METHODS: A multicentre  cross-sectional study was
      conducted at 18 family practice clinics of Aga Khan Hospital, Karachi, Pakistan.
      A total of 600 adult patients (aged over 18 years and visiting the clinic for
      more than a year) were approached consecutively to take part in this study. A pre
      tested structured questionnaire  including the EUROPEP was used by trained
      medical graduates to collect patient information. Data were analysed using SPSS
      v. 19; the internal consistency and reliability of the EUROPEP were tested. Means
      and proportions were reported for individual items of the questionnaire and a P
      value  of < 0.05 was considered statistically significant. RESULTS: Of 600
      patients, 502 (83.67%) agreed to participate and were interviewed. About one
      third (72.3%) were females and 38% were within the age group 35-50 years. The
      overall mean scale score on EUROPEP was 82.8 (+/-  18.0), the score was higher
      for females at 83.7 (+/- 17.4) points. The three statements that were most highly
      rated for assessing family practice care were listening to the patient (mean =
      4.54, SD = 0.92), thoroughness (mean score = 4.46, SD = 0.04) and proper physical
      examination (mean  score = 4.44, SD = 1.07). The poorly rated statements were
      waiting time (excellent 9.8% vs poor 45.6%) and physician not accessible on
      telephone (36.5% excellent vs 35.5% poor). CONCLUSION: The results of this study
      identified some areas of improvement in family practice, such as  accessibility
      of family practice on telephone and reduction in waiting times. Strategies should
      be devised regarding these issues at continuous medical education platform so
      that these attributes can be adapted to improve the overall quality of care.

PMID- 23114006
TI  - Early gametocytes of the malaria parasite Plasmodium falciparum specifically
      remodel the adhesive properties of infected erythrocyte surface.
AB  - In Plasmodium falciparum infections the parasite transmission stages, the
      gametocytes, mature in 10 days sequestered in internal organs. Recent studies
      suggest that cell mechanical properties rather than adhesive interactions play a
      role in sequestration during gametocyte maturation. It remains instead obscure
      how sequestration is established, and how the earliest sexual stages,
      morphologically similar to asexual trophozoites, modify the infected erythrocytes
      and their cytoadhesive properties at the onset of gametocytogenesis. Here,
      purified P. falciparum early gametocytes were used to ultrastructurally and
      biochemically analyse parasite-induced modifications on the red blood cell
      surface and to measure their functional consequences on adhesion to human
      endothelial cells. This work revealed that stage I gametocytes are able to deform
      the infected erythrocytes like asexual parasites, but do not modify its surface
      with adhesive 'knob' structures and associated proteins. Reduced levels of the P.
      falciparum erythrocyte membrane protein 1 (PfEMP1) adhesins are exposed on the
      red blood cell surface by these parasites, and the expression of the var gene
      family, which encodes 50-60 variants of PfEMP1, is dramatically downregulated in
      the transition from asexual development to gametocytogenesis. Cytoadhesion assays
      show that such gene expression changes and host cell surface modifications
      functionally result in the inability of stage I gametocytes to bind the host
      ligands used by the asexual parasite to bind endothelial cells. In conclusion,
      these results identify specific differences in molecular and cellular mechanisms
      of host cell remodelling and in adhesive properties, leading to clearly distinct
      host parasite interplays in the establishment of sequestration of stage I
      gametocytes and of asexual trophozoites.

PMID- 23114007
TI  - Fear conditioning-related changes in cerebellar Purkinje cell activities in
      goldfish.
AB  - BACKGROUND: Fear conditioning-induced changes in cerebellar Purkinje cell
      responses to a conditioned stimulus have been reported in rabbits. It has been
      suggested that synaptic long-term potentiation and the resulting increases in
      firing rates of Purkinje cells are related to the acquisition of conditioned fear
      in mammals. However, Purkinje cell activities during acquisition of conditioned
      fear have not been analysed, and changes in Purkinje cell activities throughout
      the development of conditioned fear have not yet been investigated. In the
      present study, we tracked Purkinje cell activities throughout a fear conditioning
      procedure and aimed to elucidate further how cerebellar circuits function during
      the acquisition and expression of conditioned fear. METHODS: Activities of single
      Purkinje cells in the corpus cerebelli were tracked throughout a classical fear
      conditioning procedure in goldfish. A delayed conditioning paradigm was used with
      cardiac deceleration as the conditioned response. Conditioning-related changes of
      Purkinje cell responses to a conditioned stimulus and unconditioned stimulus were
      examined. RESULTS: The majority of Purkinje cells sampled responded to the
      conditioned stimulus by either increasing or decreasing their firing rates before
      training. Although there were various types of conditioning-related changes in
      Purkinje cells, more than half of the cells showed suppressed activities in
      response to the conditioned stimulus after acquisition of conditioned fear.
      Purkinje cells that showed unconditioned stimulus-coupled complex-spike firings
      also exhibited conditioning-related suppression of simple-spike responses to the
      conditioned stimulus. A small number of Purkinje cells showed increased
      excitatory responses in the acquisition sessions. We found that the magnitudes of
      changes in the firing frequencies of some Purkinje cells in response to the
      conditioned stimulus correlated with the magnitudes of the conditioned responses
      on a trial-to-trial basis. CONCLUSIONS: These results demonstrate that Purkinje
      cells in the corpus cerebelli of goldfish show fear conditioning-related changes
      in response to a stimulus that had been emotionally neutral prior to
      conditioning. Unconditioned stimulus-induced climbing fibre inputs to the
      Purkinje cells may be involved in mediating these plastic changes.

PMID- 23114008
TI  - Bronchoalveolar hemostasis in lung injury and acute respiratory distress
      syndrome.
AB  - Enhanced intrapulmonary fibrin deposition as a result of abnormal broncho
      alveolar fibrin turnover is a hallmark of acute respiratory distress syndrome
      (ARDS), pneumonia and ventilator-induced lung injury (VILI), and is important to
      the pathogenesis of these conditions. The mechanisms that contribute to alveolar
      coagulopathy are localized tissue factor-mediated thrombin generation, impaired
      activity of natural coagulation inhibitors and depression of bronchoalveolar
      urokinase plasminogen activator-mediated fibrinolysis, caused by the increase of
      plasminogen activator inhibitors. There is an intense and bidirectional
      interaction between coagulation and inflammatory pathways in the bronchoalveolar
      compartment. Systemic or local administration of anticoagulant agents (including
      activated protein C, antithrombin and heparin) and profibrinolytic agents (such
      as plasminogen activators) attenuate pulmonary coagulopathy. Several preclinical
      studies show additional anti-inflammatory effects of these therapies in ARDS and
      pneumonia.

PMID- 23114009
TI  - Oral anticoagulant and antiplatelet drugs used in prevention of cardiovascular
      events in elderly people in Poland.
AB  - BACKGROUND: In Poland, the prevalence of cardiovascular diseases is increasing.
      This might be associated with the constantly growing proportion of elderly people
      and inappropriate cardiovascular prevention. This study aimed to evaluate the
      frequency of use of oral antiplatelet (OAP) and oral anticoagulant (OAC) drugs
      among older people in Poland and to assess their association with cardiovascular
      risk factors. METHODS: The study was based on data collected during the
      implementation of a multicentre, publicly funded research project called
      PolSenior. RESULTS: The study group consisted of 4,979 people with the average
      age of 79.35 +/- 8.69 years. Among them, 1,787 people (35.9%) used at least one
      drug in the prevention of cardiovascular diseases. OAPs were used regularly by
      1,648 (33.1%) elderly people and OACs were used by 165 elderly people (3.3%).
      Acetylsalicylic acid was used by 32.2% of elderly people. Use of drugs
      significantly depended on age (p < 0.01), sex (p < 0.01), place of residence (p <
      0.001), level of education (p < 0.0001) and personal income (p < 0.0001). Among
      all the respondents treated with OAPs, therapy was applied as secondary
      cardiovascular prevention in 717 respondents (43.5%), and as primary prevention
      in 705 respondents (42.8%). Among the respondents treated with OACs, 117 (71%)
      elderly people had a history of atrial fibrillation. Secondary cardiovascular
      prevention should be considered in a further 482 respondents (15.1% of untreated
      elderly people), and primary cardiovascular prevention in 1,447 respondents
      (45.3%). CONCLUSIONS: Our study is the first to determine the frequency of use of
      OAP and OAC drugs among elderly people in Poland in relation to cardiovascular
      risk factors. The most commonly used drug for cardiovascular prevention is
      acetylsalicylic acid, but it appears that it is used too rarely in high-risk
      patients. Educational programs should be developed among general practitioners
      concerning current recommendations for pharmacological cardiovascular prevention.

PMID- 23114010
TI  - Prevalence of depression and utilization of health care in single and multiple
      morbidity: a population-based cohort study.
AB  - BACKGROUND: This study aimed to determine whether depression in patients with
      long-term conditions is associated with the number of morbidities or the type of
      co-morbidity. Method A cohort study of 299 912 participants aged 30-100 years.
      The prevalence of depression, rates of health-care utilization and costs were
      evaluated in relation to diagnoses of diabetes mellitus (DM), coronary heart
      disease (CHD), stroke and colorectal cancer. RESULTS: The age-standardized
      prevalence of depression was 7% in men and 14% in women with no morbidity. The
      frequency of depression increased in single morbidities including DM (men 13%,
      women 22%), CHD (men 15%, women 24%), stroke (men 14%, women 26%) or colorectal
      cancer (men 10%, women 21%). Participants with concurrent diabetes, CHD and
      stroke had a very high prevalence of depression (men 23%, women 49%). The
      relative rate of depression for one morbidity was 1.63 [95% confidence interval
      (CI) 1.59-1.66], two morbidities 1.96 (95% CI 1.89-2.03) and three morbidities
      2.35 (95% CI 2.03-2.59). Compared to those with no morbidity, depression was
      associated with higher rates of health-care utilization and increased costs at
      any level of morbidity. In women aged 55 to 64 years without morbidity, the mean
      annual health-care cost was L513 without depression and L1074 with depression;
      when three morbidities were present, the cost was L1495 without depression and
      L2878 with depression. CONCLUSIONS: Depression prevalence and health-care costs
      are more strongly associated with the number of morbidities than the nature of
      the co-morbid diagnosis.

PMID- 23114011
TI  - Myotubularin family phosphatase ceMTM3 is required for muscle maintenance by
      preventing excessive autophagy in Caenorhabditis elegans.
AB  - BACKGROUND: Autophagy is a ubiquitous cellular process responsible for the bulk
      degradation of cytoplasmic components through the autophagosomal-lysosomal
      pathway. In skeletal muscle, autophagy has been regarded as a key regulator for
      muscle mass maintenance, and its imbalance leads to sarcopenia. However, the
      underlying mechanism is poorly understood. RESULTS: In this study, we demonstrate
      that ceMTM3, a FYVE-domain containing myotubalarin family phosphatase, is
      required for the maintenance of muscle fibers by preventing excessive autophagy
      in Caenorhabditis elegans. Knockdown of ceMTM3 by using feeding-based RNA
      interference caused loss of muscle fibers accompanied by shortening of muscle
      cell and body size in aged C. elegans worms. This was preceded by the occurrence
      of excessive autophagy in the muscle and other tissues, which subsequently
      resulted in increased lysosomal activity and necrotic cell death. However,
      knockdown of ceMTM3 did not aggravate the abnormalities of muscle wasting in
      autophagy-deficient atg-18 mutant worms. CONCLUSIONS: Our data suggest an
      important role of ceMTM3 in regulating autophagy and maintaining muscle fibers.
      This study may have clinical implications for prevention and treatment of
      sarcopenia.

PMID- 23114013
TI  - Dielectric response of nanoscopic spherical colloids in alternating electric
      fields: a dissipative particle dynamics simulation.
AB  - We study the response of single nanosized spherical colloids in electrolyte
      solution to an alternating electric field (AC field) by computer simulations. We
      use a coarse-grained mesoscopic simulation approach that accounts in full for
      hydrodynamic and electrostatic interactions as well as for thermal fluctuations.
      The solvent is modeled as a fluid of single dissipative particle dynamics (DPD)
      beads, and the colloidal particle is modeled as a rigid body made of DPD beads.
      We compute the mobility and the polarizability of a single colloid and
      investigate systematically the effect of amplitude and frequency of the AC
      fields. Even though the thickness of the Debye layer is not 'thin' compared to
      the radius of the colloid, and the thermal fluctuations are significant, the
      results are in good agreement with the theoretical prediction of the Maxwell
      Wagner-O'Konski theory, especially for uncharged colloids.

PMID- 23114014
TI  - Beyond the genome and into the clinic.
AB  - A report of BioMed Central's third annual Beyond the Genome conference, held at
      Harvard Medical School, Boston, September 27-29, 2012. 

PMID- 23114012
TI  - Multiparameter behavioral profiling reveals distinct thermal response regimes in
      Caenorhabditis elegans.
AB  - BACKGROUND: Responding to noxious stimuli by invoking an appropriate escape
      response is critical for survival of an organism. The sensations of small and
      large changes in temperature in most organisms have been studied separately in
      the context of thermotaxis and nociception, respectively. Here we use the
      nematode C. elegans to address the neurogenetic basis of responses to thermal
      stimuli over a broad range of intensities. RESULTS: C. elegans responds to
      aversive temperature by eliciting a stereotypical behavioral sequence. Upon
      sensation of the noxious stimulus, it moves backwards, turns and resumes forward
      movement in a new direction. In order to study the response of C. elegans to a
      broad range of noxious thermal stimuli, we developed a novel assay that allows
      simultaneous characterization of multiple aspects of escape behavior elicited by
      thermal pulses of increasing amplitudes. We exposed the laboratory strain N2, as
      well as 47 strains with defects in various aspects of nervous system function, to
      thermal pulses ranging from DeltaT = 0.4 degrees C to 9.1 degrees C and recorded
      the resulting behavioral profiles. CONCLUSIONS: Through analysis of the
      multidimensional behavioral profiles, we found that the combinations of molecules
      shaping avoidance responses to a given thermal pulse are unique. At different
      intensities of aversive thermal stimuli, these distinct combinations of molecules
      converge onto qualitatively similar stereotyped behavioral sequences.

PMID- 23114015
TI  - Exploring the link between herpes viruses and pemphigus vulgaris: literature
      review and commentary.
AB  - Pemphigus vulgaris (PV) is an autoimmune skin condition characterized by the
      presence of circulating autoantibodies specific for a subset of cellular adhesion
      proteins within mucosal and/or non-mucosal epidermal surfaces. Although the
      presence of self-directed antibodies is well established, the exact etiology of
      PV is still uncertain. Environmental factors have been linked to a variety of
      autoimmune disorders. Specifically, viral infection has been considered to act as
      one contributory component in disease pathogenesis. Perhaps the most studied
      group of pathogens is that of herpes viruses, with considerable evidence linking
      the herpes simplex virus and PV. These viruses have been reported to influence
      the course of disease and have been associated with PV flares and clinical
      exacerbations. However, there are significant inconsistencies amongst published
      data; additional analysis is required to solidify the proposed relationship. In
      the following article, we critically review the literature regarding the impact
      of the herpes viruses on PV, providing a framework for clinical application,
      mechanistic pathways, and future investigation.

PMID- 23114017
TI  - Colloidal dispersions in external fields.

PMID- 23114016
TI  - Evaluation of Helicobacter Pylori eradication in pediatric patients by triple
      therapy plus lactoferrin and probiotics compared to triple therapy alone.
AB  - BACKGROUND: To evaluate whether the addition of a probiotic could improve
      Helicobacter pylori (H.P.) eradication rates and reduce the side effects of
      treatment in children. METHODS: Between July 2008 and July 2011 all patients with
      a clinical, laboratory and endoscopic diagnosis of H.P. positive gastritis
      referred to our Unit were included in the study. Patients suffering from allergy
      to any of drugs used in the study, with previous attempts to eradicate H.P. and
      those who received antibiotics, PPIs or probiotics within 4 weeks were excluded
      from the present study. Patients were randomized into two therapy regimens (group
      A and B): both groups received standard triple treatment (omeprazole, amoxicillin
      and clarithromycin) while only group B patients were also given a probiotic
      (Probinul - Cadigroup). Patients compliance was evaluated at the end of the
      treatment. Successful eradication was defined as a negative 13 C-urea breath test
      (C13-ubt) result four weeks after therapy discontinuation. RESULTS: A total of 68
      histopathologically proven H.P.-infection children (32 male and 36 females) were
      included in the study. All of the patients in both groups used more than 90% of
      the therapies and no patients were lost at follow up. All side effects were
      selflimiting and disappeared once the therapy was terminated. Epigastric pain was
      observed in 6 (17.6%) group A vs 2 (5.8%) group B patients (P<0.05), nausea in 3
      (8.8%) group A vs 1 (2.9%) group B patients (P<0.05); vomiting and diarrhea were
      observed in 2(5.8%) and 8 (23.5%) group A patients, respectively and never in
      group B (P<0.05). There was no significant difference between the two groups in
      terms of constipation (5.8% in group A and B). Four weeks after the completion of
      therapy, 56/68 patients (82.3%) tested negative for H.P. on C13-ubt. H.P. was
      eradicated in 26 patients (76.4%) in group A and in 30 patients (88.2%) in group
      B. There was no significantly difference in the rate of H.P. eradication between
      group A and group B (p=0.1), although the success rate for H.P. eradication was
      higher in group B than in group A. CONCLUSION: The addition of a probiotic
      formula to triple therapy significantly decreased the frequency of epigastric
      pain, nausea, vomiting and diarrhea.

PMID- 23114018
TI  - Overuse of paracetamol caffeine aspirin powders affects cerebral glucose
      metabolism in chronic migraine patients.
AB  - BACKGROUND AND PURPOSE: Overuse of analgesic plays a prominent role in migraine
      chronification. Paracetamol caffeine aspirin (PCA) powders are commonly used in
      Chinese migraineurs. This study investigated the effects of the specific
      combination analgesic on cerebral glucose metabolism in chronic migraine (CM).
      METHODS: 18F-FDG-PET was used to measure regional metabolism in all subjects.
      Brain metabolisms of CM patients with analgesic overuse (AO-CM; n=10), no
      analgesic overuse (NAO-CM; n=10), and no regimen (NR-CM; n=10) and 17 age- and
      gender-matched normal controls (NC) were compared using statistical parametric
      mapping. Then, all patients underwent brain MRI analysis within 7 days after PET
      scans, as well as MMSE and MoCA scale for cognitive function tests. RESULTS:
      Glucose metabolic changes in CM patients taking different dosage of analgesic
      during headache-free periods and clear distinctions in several brain regions were
      observed. Patients with AO-CM exhibited significant metabolic reductions in
      thalamus, as well as increased metabolism in middle temporal gyrus and insula
      relative to NR-CM and NAO-CM. However, in these regions, no difference was
      observed in AO-CM except for increased metabolism in the right insula relative to
      NC group. CONCLUSIONS: Overusing PCA powders affects regional brain glucose
      metabolism in CM. Increased metabolism in the right insula may be associated with
      recurrently overusing of PCA powders.

PMID- 23114019
TI  - Herpes zoster is associated with an increased risk of subsequent lymphoid
      malignancies - a nationwide population-based matched-control study in Taiwan.
AB  - BACKGROUND: Infectious agents have been shown to contribute to the development of
      lymphoid malignancies. The different distribution of lymphoid malignancies in
      Asian and Western populations suggests possibly different etiologies in Asian
      populations. Herpes zoster infection, commonly seen in immunocompromised persons,
      has been reported to be associated with lymphoid malignancies in retrospective
      case-control studies from Western populations, but the results are controversial
      and large-scale prospective studies from Asian populations are lacking. METHODS:
      A nationwide population-based matched-controlled prospective study on Taiwanese
      patients was performed using the National Health Insurance Research Database from
      1996 to 2007. Herpes zoster and malignancies were defined by compatible ICD-9-CM
      (International Classification of Disease, 9th Revision, Clinical Modification)
      codes. Patients who had been diagnosed with any malignancies before herpes
      zoster, with known viral infections including human immunodeficiency virus, and
      duration from herpes zoster to diagnosis of malignancies less than 6 months were
      excluded. RESULTS: Of 42,498 patients with herpes zoster prior to the diagnosis
      of any malignancies, the cumulative incidence for lymphoid malignancies was 0.11%
      (n = 48), compared with 0.06% (n = 106) in 169,983 age- and gender-matched
      controls (univariate hazard ratio (HR): 1.82, 95%CI: 1.29-2.55). The most common
      lymphoid malignancy was non-Hodgkin's lymphoma (60.4%, n = 29), followed by
      multiple myeloma (27.1%, n = 13). Risk for developing lymphoid malignancies is
      significantly higher in herpes zoster patients (log rank P = 0.005). After
      adjusting for presence of any comorbidities in Charlson comorbidity index, time
      dependent covariate for herpes group, and income category using Cox proportional
      hazard regressions, herpes zoster patients had an increased risk of developing
      lymphoid malignancies (adjusted HR: 1.68, 95%CI: 1.35-2.42, P = 0.0026), but did
      not have an increased risk of developing non-lymphoid malignancies (adjusted HR:
      1.00, 95%CI: 0.91-1.05, P = 0.872). CONCLUSION: Preceding herpes zoster infection
      is an independent risk marker for subsequent lymphoid malignancies in Taiwanese
      subjects. Further studies are warranted for pathogenesis exploration and
      preventive strategies in Asian populations.

PMID- 23114020
TI  - Prevalence and correlates of hyperglycemia in a rural population, Vietnam:
      implications from a cross-sectional study.
AB  - BACKGROUND: Despite the increasing prevalence of type 2 diabetes in urban areas,
      relatively little has been known about its actual prevalence and its associations
      in rural areas, Vietnam. The purpose of this study was to evaluate the prevalence
      of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), diabetes and
      their risk factors in a rural province, Vietnam. METHODS: A cross-sectional study
      with a representative sample was designed to estimate the hyperglycemia
      prevalence, using 75-g oral glucose tolerance test. Potential risk factors for
      hyperglycemia were analyzed using multinomial logistic regression, taken into
      account influences of socio-economic status, anthropometric measures, and
      lifestyle-related factors. RESULTS: The age and sex-adjusted prevalence rates
      (95% CI) of isolated IFG, isolated IGT, combined IFG-IGT, and diabetes were 8.7
      (7.0-10.5), 4.3 (3.2-5.4), 1.6 (0.9-2.3), and 3.7% (2.7-4.7%), respectively.
      There were still 73% of diabetic subjects without knowing the condition. Blood
      pressure, family history of diabetes, obesity-related measures (waist
      circumference, waist-hip ratio, body fat percentage, and abdominal obesity) were
      the independent risk factors for hyperglycemia (IFG, IGT, and diabetes).
      CONCLUSIONS: The prevalence of hyperglycemia in rural areas has not been as
      sharply increased as that reported in urban cities, Vietnam. Blood pressure and
      obesity-related measures were the most significant predictors for hyperglycemia
      level and they can be taken into account in building prognosis models to early
      detection of diabetes in rural Vietnamese populations.

PMID- 23114021
TI  - Recruitment strategies for the detection of individuals at clinical high risk of
      developing psychosis.

PMID- 23114022
TI  - Family history of venous thromboembolism (VTE) as a predictor for recurrent VTE
      in unprovoked VTE patients.

PMID- 23114023
TI  - The pro-atherogenic effects of macrophages are reduced upon formation of a
      complex between C-reactive protein and lysophosphatidylcholine.
AB  - RATIONALE: C-reactive protein (CRP) and lysophosphatidylcholine (LPC) are
      phosphorylcholine-(PC)-containing oxidized phospholipids (oxPLs) found in
      oxidized LDL (oxLDL), which trigger pro-atherogenic activities of macrophages
      during the process of atherosclerosis. It has been previously reported that CRP
      binds to the PC head group of oxLDL in a calcium-dependent manner. The aim of
      this study was to investigate the importance of binding between CRP and LPC to
      the pro-atherogenic activities of macrophages. OBJECTIVES AND FINDINGS: A
      chemiluminescent immunoassay and HPLC showed that human recombinant CRP formed a
      stable complex with LPC in the presence of calcium. The Kd value of the binding
      of the CRP-LPC complex to the receptors FcgammaRIA or FcgammaRIIA was 3-5 fold
      lower than that of CRP alone. The CRP-LPC complex triggered less potent
      generation of reactive oxygen species and less activation of the transcription
      factors AP-1 and NF-kB by human monocyte-derived macrophages in comparison to CRP
      or LPC alone. However, CRP did not affect activities driven by components of
      oxLDL lacking PC, such as upregulation of PPRE, ABCA1, CD36 and PPARgamma and the
      enhancement of cholesterol efflux by human macrophages. The presence of CRP
      inhibited the association of Dil-labelled oxLDL to human macrophages.
      CONCLUSIONS: The formation of complexes between CRP and PC-containing oxPLs, such
      as LPC, suppresses the pro-atherogenic effects of CRP and LPC on macrophages.
      This effect may in part retard the progression of atherosclerosis.

PMID- 23114024
TI  - Estimating variation within the genes and inferring the phylogeny of 186
      sequenced diverse Escherichia coli genomes.
AB  - BACKGROUND: Escherichia coli exists in commensal and pathogenic forms. By
      measuring the variation of individual genes across more than a hundred sequenced
      genomes, gene variation can be studied in detail, including the number of
      mutations found for any given gene. This knowledge will be useful for creating
      better phylogenies, for determination of molecular clocks and for improved typing
      techniques. RESULTS: We find 3,051 gene clusters/families present in at least 95%
      of the genomes and 1,702 gene clusters present in 100% of the genomes. The former
      'soft core' of about 3,000 gene families is perhaps more biologically relevant,
      especially considering that many of these genome sequences are draft quality. The
      E. coli pan-genome for this set of isolates contains 16,373 gene clusters.A core
      gene tree, based on alignment and a pan-genome tree based on gene
      presence/absence, maps the relatedness of the 186 sequenced E. coli genomes. The
      core-gene tree displays high confidence and divides the E. coli strains into the
      observed MLST type clades and also separates defined phylotypes. CONCLUSION: The
      results of comparing a large and diverse E. coli dataset support the theory that
      reliable and good resolution phylogenies can be inferred from the core-genome.
      The results further suggest that the resolution at the isolate level may,
      subsequently be improved by targeting more variable genes. The use of whole
      genome sequencing will make it possible to eliminate, or at least reduce, the
      need for several typing steps used in traditional epidemiology.

PMID- 23114025
TI  - Comparison of approaches to estimate confidence intervals of post-test
      probabilities of diagnostic test results in a nested case-control study.
AB  - BACKGROUND: Nested case-control studies become increasingly popular as they can
      be very efficient for quantifying the diagnostic accuracy of costly or invasive
      tests or (bio)markers. However, they do not allow for direct estimation of the
      test's predictive values or post-test probabilities, let alone for their
      confidence intervals (CIs). Correct estimates of the predictive values itself can
      easily be obtained using a simple correction by the (inverse) sampling fractions
      of the cases and controls. But using this correction to estimate the
      corresponding standard error (SE), falsely increases the number of patients that
      are actually studied, yielding too small CIs. We compared different approaches
      for estimating the SE and thus CI of predictive values or post-test probabilities
      of diagnostic test results in a nested case-control study. METHODS: We created
      datasets based on a large, previously published diagnostic study on 2 different
      tests (D-dimer test and calf difference test) with a nested case-control design.
      We compared six different approaches; the approaches were: 1. the standard
      formula for the SE of a proportion, 2. adaptation of the standard formula with
      the sampling fraction, 3. A bootstrap procedure, 4. A approach, which uses the
      sensitivity, the specificity and the prevalence, 5. Weighted logistic regression,
      and 6. Approach 4 on the log odds scale. The approaches were compared with
      respect to coverage of the CI and CI-width. RESULTS: The bootstrap procedure
      (approach 3) showed good coverage and relatively small CI widths. Approaches 4
      and 6 showed some undercoverage, particularly for the D-dimer test with frequent
      positive results (positive results around 70%). Approaches 1, 2 and 5 showed
      clear overcoverage at low prevalences of 0.05 and 0.1 in the cohorts for all case
      control ratios. CONCLUSION: The results from our study suggest that a bootstrap
      procedure is necessary to assess the confidence interval for the predictive
      values or post-test probabilities of diagnostic tests results in studies using a
      nested case-control design.

PMID- 23114026
TI  - Persisting role of healthcare settings in hepatitis C transmission in Pakistan:
      cause for concern.
AB  - Transmission of hepatitis C (HCV) in Pakistan is a continuing public health
      problem; 15 years ago it was linked to the practice of reusing therapeutic
      instruments in healthcare settings. We sought to examine current risk factors for
      HCV transmission in a hospital population in Karachi, Pakistan. We enrolled 300
      laboratory-confirmed HCV-positive participants and 300 laboratory confirmed HCV
      negative participants from clinics at Indus Hospital. Independent and significant
      risk factors for both men and women were: receiving o12 injections in the past
      year, blood transfusions, having had dental work performed, and delivery in
      hospital or transfusion for women. Interestingly, being of Mohajir origin or born
      in Sindh province were protective.Encouragingly, a strong protective effect was
      observed for those that reported bringing their own needle for injections (59%).
      The widespread reuse of therapeutic needles in healthcare settings in Karachi
      remains a major driver of the HCV epidemic.

PMID- 23114028
TI  - Fatty liver disease and hypertransaminasemia hiding the association of clinically
      silent Duchenne muscular dystrophy and hereditary fructose intolerance.
AB  - We report a case with the association of well self-compensated hereditary
      fructose intolerance and still poorly symptomatic Duchenne type muscular
      dystrophy. This case illustrates the problems of a correct diagnosis in sub
      clinical patients presenting with "cryptogenic" hypertransaminasemia.

PMID- 23114029
TI  - Early evolution of efficient enzymes and genome organization.
AB  - BACKGROUND: Cellular life with complex metabolism probably evolved during the
      reign of RNA, when it served as both information carrier and enzyme. Jensen
      proposed that enzymes of primordial cells possessed broad specificities: they
      were generalist. When and under what conditions could primordial metabolism run
      by generalist enzymes evolve to contemporary-type metabolism run by specific
      enzymes? RESULTS: Here we show by numerical simulation of an enzyme-catalyzed
      reaction chain that specialist enzymes spread after the invention of the
      chromosome because protocells harbouring unlinked genes maintain largely non
      specific enzymes to reduce their assortment load. When genes are linked on
      chromosomes, high enzyme specificity evolves because it increases biomass
      production, also by reducing taxation by side reactions. CONCLUSION: The
      constitution of the genetic system has a profound influence on the limits of
      metabolic efficiency. The major evolutionary transition to chromosomes is thus
      proven to be a prerequisite for a complex metabolism. Furthermore, the appearance
      of specific enzymes opens the door for the evolution of their regulation.
      REVIEWERS: This article was reviewed by Sandor Pongor, Gaspar Jekely, and Rob
      Knight.

PMID- 23114030
TI  - Update on clinical and laboratory features in necrobiosis lipoidica: a
      retrospective multicentre study of 52 patients.
AB  - Necrobiosis lipoidica (NL) is a rare granulomatous disorder of unknown etiology
      which can manifest in ulcerative skin lesions and is widely recognised in
      association with diabetes mellitus. Our aim was to improve knowledge about the
      epidemiology and clinical course of NL and evaluate treatment approaches. This
      multicentre retrospective study covered data from 52 patients with NL of the
      lower leg, treated between 2006 and 2011. Data from three German dermatological
      centres were analysed. Twelve men and 40 women, aged 15 to 87 years, were
      evaluated with regard to epidemiological data, ulcerations, co-morbidities,
      laboratory values and treatment options. NL was significantly more frequent in
      women (76.9%). Ulceration of NL was observed in 25% of all patients and in 37.5%
      with concomitant diabetes mellitus. 88% received topical treatment with
      corticosteroids, 56% compression therapy of the lower legs, 42% UV-phototherapy
      and 29% topical calcineurininhibitors. Systemic therapies were also used
      occasionally. Our data indicate that female sex, middle age and endocrine
      disorders like diabetes mellitus are characteristics of NL patients. As new
      aspects, we found an accumulation of thyroidal dysfunction (13%) and that
      ulcerations are predominantly in males (58%). Associations with co-morbidities
      may become clearer in prospective studies of larger cohorts. Topical steroids,
      calcineurin inhibitors, compression therapy and phototherapy seem to be the basis
      therapies although our evaluation showed that standardized guidelines are
      missing. More experimental therapeutic options, like biologicals, photodynamic
      therapy or the use of fumaric acid esters, should be assessed for efficacy and
      safety by large, randomized, controlled trials.

PMID- 23114031
TI  - The effects of C-type natriuretic peptide on craniofacial skeletogenesis.
AB  - C-type natriuretic peptide (CNP) is a potent stimulator of long bone and
      vertebral development via endochondral ossification. In the present study, we
      investigated the effects of CNP on craniofacial skeletogenesis, which consists of
      both endochondral and membranous ossification. Morphometric analyses of crania
      from CNP knockout and transgenic mice revealed that CNP stimulates longitudinal
      growth along the cranial length, but does not regulate cranial width. CNP
      markedly increased the length of spheno-occipital synchondrosis in fetal murine
      organ cultures, and the thickness of cultured murine chondrocytes from the spheno
      occipital synchondrosis or nasal septum, resulting in the stimulation of
      longitudinal cranial growth. Mandibular growth includes endochondral and
      membranous ossification; although CNP stimulated endochondral bone growth of
      condylar cartilage in cultured fetal murine mandibles, differences in the lengths
      of the lower jaw between CNP knockout or transgenic mice and wild-type mice were
      smaller than those observed for the lengths of the upper jaw. These results
      indicate that CNP primarily stimulates endochondral ossification in the
      craniofacial region and is crucial for midfacial skeletogenesis.

PMID- 23114032
TI  - Endothelial differentiation of SHED requires MEK1/ERK signaling.
AB  - The discovery that dental pulp stem cells are capable of differentiating into
      endothelial cells raises the exciting possibility that these cells can be a
      single source of odontoblasts and vascular networks in dental tissue engineering.
      The purpose of this study was to begin to define signaling pathways that regulate
      endothelial differentiation of SHED. Stem cells from exfoliated deciduous teeth
      (SHED) exposed to endothelial growth medium (EGM-2MV) supplemented with vascular
      endothelial growth factor (VEGF) differentiated into VEGFR2-positive and CD31
      positive endothelial cells in vitro. In vivo, VEGFR1-silenced SHED seeded in
      tooth slice/ scaffolds and transplanted into immunodeficient mice showed a
      reduction in human CD31-positive blood vessels as compared with controls (p =
      0.02). Exposure of SHED to EGM2-MV supplemented with VEGF induced potent
      activation of ERK and Akt signaling, while it inhibited phosphorylation of STAT3.
      Notably, genetic (MEK1 silencing) or chemical (U0126) inhibition of ERK signaling
      restored constitutive STAT3 phosphorylation and inhibited the differentiation of
      SHED into endothelial cells. Collectively, analysis of these data unveiled the
      VEGF/MEK1/ERK signaling pathway as a key regulator of the endothelial
      differentiation of dental pulp stem cells.

PMID- 23114033
TI  - Potential mechanism for the laser-fluoride effect on enamel demineralization.
AB  - Laser-induced prevention of dental caries has been studied extensively. However,
      the cariostatic mechanisms of a combined fluoride-laser treatment are not well
      understood. Using micro- computed tomography (micro-CT), we quantified the effect
      of fluoride and/or Er:YAG laser treatment on enamel demineralization. The mean
      mineral loss (%/V) for each group was 4,870 +/- 1,434 (fluoride followed by laser
      treatment), 6,341 +/- 2,204 (laser treatment), 7,669 +/- 2,255 (fluoride
      treatment), and 10,779 +/- 2,936 (control). The preventive effect of the laser (p
      < 0.001) and fluoride (p = 0.010) treatment was statistically significant.
      Characterized by micro-x-ray diffraction (XRD) analysis, the significant
      contraction in the a-axis after both laser and combined laser/fluoride treatment
      was revealed (both p < 0.05). In conclusion, subablative low-energy Er:YAG laser
      irradiation following fluoride treatment may instantaneously transform enamel
      hydroxyapatite into fluoridated hydroxyapatite to reduce enamel solubility as a
      preventive treatment for enamel demineralization.

PMID- 23114034
TI  - Personalized medicine in women's obesity prevention and treatment: implications
      for research, policy and practice.
AB  - The prevalence of obesity in America has reached epidemic proportions, and
      obesity among women is particularly concerning. Severe obesity (body mass index
      >=35 kg m(-2) ) is more prevalent in women than men. Further, women have sex
      specific risk factors that must be considered when developing preventive and
      therapeutic interventions. This review presents personalized medicine as a
      dynamic approach to obesity prevention, management and treatment for women.
      First, we review obesity as a complex health issue, with contributing sex
      specific, demographic, psychosocial, behavioural, environmental, epigenetic and
      genetic/genomic risk factors. Second, we present personalized medicine as a
      rapidly advancing field of health care that seeks to quantify these complex risk
      factors to develop more targeted and effective strategies that can improve
      disease management and/or better minimize an individual's likelihood of
      developing obesity. Third, we discuss how personalized medicine can be applied in
      a clinical setting with current and emerging tools, including health risk
      assessments, personalized health plans, and strategies for increasing patient
      engagement. Finally, we discuss the need for additional research, training and
      policy that can enhance the practice of personalized medicine in women's obesity,
      including further advancements in the '-omics' sciences, physician training in
      personalized medicine, and additional development and standardization of
      innovative targeted therapies and clinical tools.

PMID- 23114035
TI  - Broad applications of single-cell nucleic acid analysis in biomedical research.

PMID- 23114036
TI  - Depletion induced clustering in mixtures of colloidal spheres and fd-virus.
AB  - We determined the phase boundary of an ideal rod-sphere mixture consisting of fd
      virus, which is an established model system for mono-disperse colloidal rods, and
      density matched mono-disperse polystyrene beads employing diffuse wave
      spectroscopy. The low volume fraction of fd needed to induce a phase separation
      at relatively low ionic strength exemplifies the fact that slender rods are very
      effective depletion agents. Confocal microscopy showed that stable clusters are
      formed during phase separation. Relaxation after shear deformation of these
      clusters showed that the phase separation is gas-liquid-like and that the
      interfacial tension involved is very low as in colloid-polymer mixtures.

PMID- 23114037
TI  - Major life events and development of major depression in Parkinson's disease
      patients.
AB  - BACKGROUND AND PURPOSE: Non-motor symptoms including depression are important
      features of Parkinson's disease (PD). We aim to address the relationship between
      major life events and depression amongst PD patients free of depressive symptoms
      at baseline. METHODS: New-onset PD patients from California were recruited in
      2001-2007 and followed up for 3-4 years. The participants (n=221) were examined
      by neurologists and responded to comprehensive interviews that included major
      life events, social support, and coping measures from validated scales. Major
      depression was assessed using the Structured Clinical Interview for the DSM-IV
      depression module (SCID). RESULTS: More than half of all patients had experienced
      major life events since diagnosed with PD, and 22 patients developed a major
      depression. The number of life events was associated with risk of depression in
      an exposure-dependent manner, with each additional event being associated with a
      56% higher risk of depression (95% CI: 1.23-1.98). Most individual life events
      were associated with a two- to eight-fold higher risk of depression. Patients
      with low social support or coping capacities seemed to be particularly
      susceptible to developing depression after experiencing major life events.
      CONCLUSIONS: Life events play an important role for onset of depression in
      patients with PD; an effect that seems to be modulated by social support and
      coping capacities and these factors may therefore be important to assess in order
      to identify patients with PD at high risk of depression and provide effective
      interventions.

PMID- 23114038
TI  - Anatomic, hematologic, and biochemical features of C57BL/6NCrl mice maintained on
      chronic oral corticosterone.
AB  - Metabolic syndrome is a condition that typically includes central obesity,
      insulin resistance, glucose intolerance, dyslipidemia, and hypertension.
      Disruption of the hypothalamic-pituitary-adrenal axis, a regulator of
      corticosterone secretion, occurs in some cases of metabolic  syndrome and
      obesity, and Cushing hypercortisolemia is associated with obesity and metabolic
      disorders. We therefore assessed anatomic and clinical pathology in C57BL/6NCrl
      mice to evaluate the effects of chronic corticosterone in the drinking water at
      doses of 25, 50, and 100 MUg/mL for  25 d. Treated mice developed obesity,
      glucose intolerance, electrolyte aberrations, and dyslipidemia that were dose
      dependent and most severe in the 100-mu;g/mL treatment group. To evaluate return
      to normal function, additional C57BL/6NCrl mice received corticosterone-free
      water for 2 wk after  the 25-d treatment period. According to results of gross
      examination, mice appeared to recover within days of exogenous corticosterone
      withdrawal; however, adrenal gland vacuolation and protein, lipid, and
      electrolyte abnormalities persisted. Together, these findings support chronic
      corticosterone  exposure through the drinking water as a potentially useful,
      noninvasive method to induce some features of metabolic syndrome.

PMID- 23114039
TI  - Assessment of hazard risk associated with the intravenous use of viral vectors in
      rodents.
AB  - Viral vectors are emerging as potent basic research tools and gene therapy
      vehicles in many laboratory animal models. However, little information is
      available on the potential shedding of these vectors and the consequent exposure
      risk to investigators and animal care staff from animals  over time. This study
      provides empirical information to Institutional Biosafety Committees and animal
      care programs, to enhance their ability to perform risk management of laboratory
      animals treated with viral vectors. Control experiments evaluated the limit of
      detection of third-generation  lentivirus, recombinant adeno-associated virus,
      and E1-deleted adenovirus tested directly from stocks and after application onto
      cage plastic or bedding. After inoculation of ICR or NOD-SCID mice, we quantified
      the recovery of viral vector genomes directly from blood, urine, and fecal
      samples  and assessed the persistence of infectious vector at the site of
      injection and from soiled bedding at different time points after inoculation. No
      differences were seen between ICR and NOD-SCID mice. We saw no evidence of vector
      amplification after in vivo inoculation. The most environmentally  persistent
      vector was recombinant adeno-associated virus, which has no known pathogenicity
      in humans. In light of these data, we conclude that commonly used replication
      deficient viral vectors pose minimal exposure risk by 72 h after inoculation.
      Prudent precautions at Animal Biosafety Level  2 are warranted during initial
      administration, but Level 1 safety measures may be sufficient after cage changing
      and biosafety evaluation.

PMID- 23114040
TI  - Gastrointestinal microbiota and local inflammation during oxazolone-induced
      dermatitis in BALB/cA mice.
AB  - At present, laboratory animals are not standardized with regard to the
      gastrointestinal microbiota (GM), but differences in this feature may alter
      various parameters in animal models. We hypothesized that variation in the GM
      correlated with variation in clinical parameters of a murine  oxazolone-induced
      skin inflammation model of atopic dermatitis. BALB/cA mice were sensitized with
      oxazolone over a 28-d period and variation in gastrointestinal microbiota in
      fecal and cecal samples was assessed by PCR-denaturing gradient gel
      electrophoresis. Clinical parameters included transepidermal  water loss, ear
      thickness, inflammatory factors in ear tissue and plasma, and histopathologic
      evaluation. The fecal microbiota before induction of skin inflammation strongly
      correlated with the levels of some proinflammatory cytokines (IFNgamma, IL1beta,
      IL12, and TNFalpha), the antiinflammatory  cytokines IL4 and IL10, and the
      chemokine KC/GRO that were measured in ear samples at study termination. Cecal
      microbiota at termination correlated with ear thickness and transepidermal water
      loss. There was no correlation between cytokine responses and ear thickness or
      transepidermal water  loss. In addition, GM changed during the study period in
      the oxazolone-treated mice, whereas this was not the case for the control mice.
      The current study shows that the GM of mice influences the development of
      oxazolone-induced skin inflammation and that the model itself likely induces a 
      pathophysiologic response that alters the composition of the GM.

PMID- 23114041
TI  - Development of standardized insulin treatment protocols for spontaneous rodent
      models of type 1 diabetes.
AB  - Standardized protocols for maintaining near-normal glycemic levels in diabetic
      rodent models for testing therapeutic agents to treat disease are unavailable. We
      developed protocols for 2 common models of spontaneous type 1 diabetes, the
      BioBreeding diabetes-prone (BBDP) rat and nonobese  diabetic (NOD) mouse. Insulin
      formulation, dose level, timing of dose administration, and delivery method were
      examined and adjusted so that glycemic levels remained within a normal range and
      fluctuation throughout feeding and resting cycles was minimized. Protamine zinc
      formulations provided  the longest activity, regardless of the source of insulin.
      Glycemic control with few fluctuations was achieved in diabetic BBDP rats through
      twice-daily administration of protamine zinc insulin, and results were similar
      regardless of whether BBDP rats were acutely or chronically diabetic at 
      initiation of treatment. In contrast, glycemic control could not be attained in
      NOD mice through administration of insulin twice daily. However, glycemic control
      was achieved in mice through daily administration of 0.25 U insulin through
      osmotic pumps. Whereas twice-daily injections of protamine  zinc insulin provided
      glycemic control with only minor fluctuations in BBDP rats, mice required
      continuous delivery of insulin to prevent wide glycemic excursions. Use of these
      standard protocols likely will aid in the testing of agents to prevent or reverse
      diabetes.

PMID- 23114042
TI  - High incidence of scrotal hernias in a closed colony of FVB mice.
AB  - Although inguinal hernias are rarely reported to occur in mice, a high incidence
      of scrotal hernias was observed in a closed breeding colony of FVB/N mice.
      Unilateral or bilateral hernias occurred in more than 20% of the male mice in the
      colony that were available for necropsy over  3 inbred and 1 outcross
      generations; no female mice were affected. Organs commonly present within the
      hernial sac included the cecum and seminal vesicles. Hernias did not adversely
      affect the fertility or lifespan of the affected male mice. Although the
      condition was heritable, no clear pattern of transmission was evident.

PMID- 23114043
TI  - A rat model of cigarette smoke abuse liability.
AB  - We sought to develop a rat model of cigarette smoke exposure (CSE) that created
      cotinine serum levels comparable to those of smokers and induced conditioned
      place preference (CPP) suggestive of cigarette smoke abuse liability. Rats were
      exposed to sidestream cigarette smoke delivered  semicontinuously for 2 periods
      of 20 (group S20), 40 (group S40), or 60 (group S60) min daily for 12 wk. Serum
      cotinine concentration in blood samples was determined at 1 and 20 h after CSE. A
      biased (black versus white chamber) CPP paradigm was used. In the high CSE group
      (group S60), serum  cotinine at 1 h (250 to 300 ng/mL) was comparable to average
      cotinine levels reported for addicted smokers (around 300 ng/mL). Cotinine levels
      at 20 h after CSE were higher than the smoker-nonsmoker cut-off value (greater
      than 14 ng/mL) in all smoking groups, with the S60 group having  the highest
      levels. All rats preferred the black chamber to the white chamber during the
      preexposure CPP test. The time spent in the white chamber was increased compared
      with 0-wk values in group S40 at 8 wk, group S60 at 4 and 8 wk, and the control
      group at 4 and 8 wk but not at 12 wk; however,  the shift in CPP was
      significantly higher at 8 wk in group S60 compared with other groups. In
      conclusion, interrupted 2-h daily CSE for 8 wk induced serum cotinine levels in
      rats comparable to those of smokers and induced CPP suggestive of cigarette smoke
      abuse liability.

PMID- 23114044
TI  - Effects of route of inoculation and viral genetic variation on antibody responses
      to polyomavirus SV40 in Syrian golden hamsters.
AB  - Genetic variants of polyomavirus SV40 are powerful agents with which to define
      viral effects on cells and carcinogenesis pathways. We hypothesized that
      differences in biologic variation among viral strains affect the process of viral
      infection and are reflected in antibody responses  to the viral nonstructural
      large T-antigen (TAg) protein but not in neutralizing antibody responses against
      the inoculated viral particles. We analyzed the production of TAg antibody and
      neutralizing antibody in Syrian golden hamsters that were inoculated with SV40
      viral strains by intracardiac,  intravenous, or intraperitoneal routes and
      remained tumor free. Compared with the intraperitoneal route, intravascular (that
      is, intravenous, intracardiac) inoculation resulted in increased frequency of
      responsiveness to TAg but not in higher TAg antibody titers. The intravascular
      route was  superior both for eliciting neutralizing antibody responses and for
      higher titers of those responses. Viruses with complex regulatory regions induced
      TAg antibody more often than did viruses with simple regulatory regions after
      intraperitoneal but not intravascular injections, with no differences  in
      antibody titers. This viral genetic variation had no effect on neutralizing
      antibody production after intraperitoneal or intravascular inoculations or on
      neutralizing antibody titers achieved. These findings confirm that SV40 variants
      differ in their biologic properties. Route of inoculation  combined with viral
      genetic variation significantly influence the development of serum antibodies to
      SV40 TAg in tumor-free hamsters. Route of inoculation-but not viral genetic
      variation-is an important factor in production of neutralizing antibody to SV40.

PMID- 23114045
TI  - Electrocardiograms corresponding to the development of myocardial infarction in
      anesthetized WHHLMI rabbits (Oryctolagus cuniculus), an animal model for familial
      hypercholesterolemia.
AB  - The aim of this study was to determine whether features indicative of myocardial
      ischemia occur in the electrocardiograms (ECG) in myocardial infarction-prone
      Watanabe heritable hyperlipidemic (WHHLMI) rabbits, an animal model for human
      familial hypercholesterolemia. ECG were recorded  in 110 anesthetized WHHLMI
      rabbits (age, 10 to 39 mo) by using unipolar and bipolar limb leads with or
      without chest leads. We noted the following electrocardiographic changes: T wave
      inversion (37.4%), ST segment depression (31.8%), deep Q wave (16.3%), reduced R
      wave amplitude (7.3%), ST  segment elevation (2.7%), and high T wave (1.8%).
      These ECG changes resembled those in human patients with coronary heart disease.
      Histopathologic examination revealed that the left ventricular wall showed acute
      myocardial lesions, including loss of cross-striations, vacuolar degeneration, 
      coagulation necrosis of cardiac myocytes, and edema between myofibrils, in
      addition to chronic myocardial lesions such as myocardial fibrosis. The coronary
      arteries that caused these ECG changes were severely stenosed due to
      atherosclerotic lesions. Ischemic ECG changes corresponded to the  locations of
      the myocardial lesions. Normal ECG waveforms were similar between WHHLMI rabbits
      and humans, in contrast to the large differences between rabbits and mice or
      rats. In conclusion, ischemic ECG changes in WHHLMI rabbits reflect the location
      of myocardial lesions, making this model  useful for studying coronary heart
      disease.

PMID- 23114046
TI  - Acute portal hypertension models in dogs: low- and high-flow approaches.
AB  - Effective animal models are needed to evaluate the feasibility of new techniques
      to assess portal hypertension (PH). Here we developed 2 canine models of acute PH
      by increasing intrasinusoidal resistance and by increasing the portal vein (PV)
      flow volume to test the efficacy of a noninvasive  technique to evaluate PH. The
      acute low-flow PH model was based on embolization of liver circulation by using a
      gelatin sponge material. The acute high-flow PH model was based on increasing the
      PV flow volume by using an arteriovenous (A-V) shunt from the femoral artery and
      saline infusion.  PV pressures and diameters were assessed before and after
      inducing PH. Pressure values and diameters were obtained from the inferior vena
      cava in 3 unmanipulated controls. The low-flow model of PH was repeatable and
      successfully increased PV pressure by an average of 16.5 mm Hg within 15 min. 
      The high-flow model of PH failed to achieve increased PV pressures. However,
      saline supplementation of the portal circulation in the high-flow model led to
      mean increases in PV pressures of 12.8 mm Hg within 20 min. Pulsatility in the PV
      was decreased in the low-flow model and increased in  the high-flow model
      relative to baseline. No changes in PV diameter were noted in either model. These
      acute PH models are relatively straightforward to implement and may facilitate
      the evaluation of new techniques to assess PH.

PMID- 23114048
TI  - Intracranial meningioma with ophthalmoplegia in a rhesus macaque (Macaca
      mulatta).
AB  - A 21-y-old female rhesus macaque presented with signs of internal and external
      ophthamoplegia, including anisocoria and ptosis. Ophthalmoplegia is the paralysis
      or weakness of one or more intraocular or extraocular muscles that control the
      movement of eye; this condition can be caused  by neurologic or muscle disorders.
      The macaque was euthanized due to progression of clinical symptoms, and
      postmortem gross examination revealed a mass at the base of the brain attached to
      the meninges. Histopathologic examination led to the diagnosis of intracranial
      meningioma. Here we describe  a case of intracranial meningioma with internal and
      external ophthalmoplegia in a rhesus macaque (Macaca mulatta).

PMID- 23114047
TI  - Acute neuronal injury and blood genomic profiles in a nonhuman primate model for
      ischemic stroke.
AB  - The goal of this study was to characterize acute neuronal injury in a novel
      nonhuman primate (NHP) ischemic stroke model by using multiple outcome measures.
      Silk sutures were inserted into the M1 segment of the middle cerebral artery of
      rhesus macaques to achieve permanent occlusion  of the vessel. The sutures were
      introduced via the femoral artery by using endovascular microcatheterization
      techniques. Within hours after middle cerebral artery occlusion (MCAO),
      infarction was detectable by using diffusion-weighted MRI imaging. The infarcts
      expanded by 24 h after MCAO and  then were detectable on T2-weighted images. The
      infarcts seen by MRI were consistent with neuronal injury demonstrated
      histologically. Neurobehavioral function after MCAO was determined by using 2
      neurologic testing scales. Neurologic assessments indicated that impairment after
      ischemia was  limited to motor function in the contralateral arm; other
      neurologic and behavioral parameters were largely unaffected. We also used
      microarrays to examine gene expression profiles in peripheral blood mononuclear
      cells after MCAO-induced ischemia. Several genes were altered in a time-dependent
      manner after MCAO, suggesting that this ischemia model may be suitable for
      identifying blood biomarkers associated with the presence and severity of
      ischemia. This NHP stroke model likely will facilitate the elucidation of
      mechanisms associated with acute neuronal injury after ischemia. In  addition,
      the ability to identify candidate blood biomarkers in NHP after ischemia may
      prompt the development of new strategies for the diagnosis and treatment of
      ischemic stroke in humans.

PMID- 23114049
TI  - Meningoencephalitis due to Listeria monocytogenes in a pregnant rhesus macaque
      (Macaca mulatta).
AB  - We here report a spontaneous case of meningoencephalitis due to Listeria
      monocytogenes in an adult primiparous rhesus macaque (Macaca mulatta) during an
      outbreak of listeriosis in an outdoor enclosure. Clinical signs included tremors,
      abnormal posture, and altered mental  status. Hematology and analyses of
      cerebrospinal fluid were consistent with bacterial infection. Pure cultures of L.
      monocytogenes were recovered from the placenta-abortus, cerebrospinal fluid, and
      brain tissue. The macaque did not respond to treatment and was euthanized.
      Histopathologic  examination of the brain revealed acute meningoencephalitis.
      This case represents an unusual clinical and pathologic presentation of
      listeriosis in a nonhuman primate in which the dam and fetus both were affected.

PMID- 23114051
TI  - Introduction: the interplay between the autonomic and immune systems.

PMID- 23114050
TI  - Evaluation of adult dTPaP vaccination coverage in France: experience in Lyon
      city, 2010-2011.
AB  - BACKGROUND: Compliance with official recommendations can be assessed by
      evaluating vaccination coverage (VC) in populations. The main objective of our
      study was to assess VC of adults against diphtheria, tetanus, poliomyelitis and
      pertussis (dTPaP) according to age. The second objective was to explore if
      vaccination status could be confirmed by documentation. METHODS: A cross
      sectional study was conducted in 680 adults consulting for biological examination
      in private laboratories in Lyon (France) to evaluate VC for diphtheria, tetanus,
      poliomyelitis and pertussis (dTPaP) and enabled reported vaccinations to be
      compared with documented, confirmed vaccinations. RESULTS: Verification of
      documented, confirmed vaccinations disclosed VC of 78.7% for tetanus, 63.6% for
      poliomyelitis, 57.8% for diphtheria and 10.7% for pertussis. Comparison of
      confirmed and self-reported vaccinations revealed that a large percentage of
      people who thought that they were vaccinated were not. VC significantly decreased
      with age for diphtheria and poliomyelitis and did not vary by gender. The VC rate
      for pertussis has increased since the 2008 recommendations were made.
      CONCLUSIONS: The main thrust of this study was to compare reported and confirmed
      data. A significant percentage of people wrongly believed that they were up to
      date with their vaccination.

PMID- 23114052
TI  - The inflammatory reflex: the current model should be revised.

PMID- 23114053
TI  - Self-assembly of colloidal particles into strings in a homogeneous external
      electric or magnetic field.
AB  - Colloidal particles with a dielectric constant (magnetic susceptibility) mismatch
      with the surrounding solvent acquire a dipole moment in a homogeneous external
      electric (magnetic) field. The resulting dipolar interactions can lead to
      aggregation of the particles into string-like clusters. Recently, several methods
      have been developed to make these structures permanent. However, especially when
      multiple particle sizes and/or more complex shapes than single spheres are used,
      the parameter space for these experiments is enormous. We therefore use Monte
      Carlo simulations to investigate the structure of the self-assembled string-like
      aggregates in binary mixtures of dipolar hard and charged spheres, as well as
      dipolar hard asymmetric dumbbells. Binary mixtures of spheres aggregate in
      different types of clusters depending on the size ratio of the spheres. For
      highly asymmetric systems, the small spheres form ring-like and flame-like
      clusters around strings of large spheres, while for size ratios closer to 1,
      alternating strings of both large and small spheres are observed. For asymmetric
      dumbbells, we investigate both the effect of size ratio and dipole moment ratio,
      leading to a large variety of cluster shapes, including chiral clusters.

PMID- 23114054
TI  - A proton magnetic resonance spectroscopic study in autism spectrum disorders:
      amygdala and orbito-frontal cortex.
AB  - We previously reported neural dysfunction in the anterior cingulate cortex and
      dorsolateral prefrontal cortex in autistic patients using proton magnetic
      resonance spectroscopy ((1)H-MRS). In this investigation, we measured chemical
      metabolites in the left amygdala and the bilateral orbito-frontal cortex (OFC),
      which are the main components of the social brain. We also examined the
      association between these metabolic findings and social abilities in subjects
      with autism. The study group included 77 autistic patients (3-6years old; mean
      age 4.1; 57 boys and 20 girls). The control subjects were 31 children (3-6years
      old; mean age 4.0; 23 boys and 8 girls). Conventional proton MR spectra were
      obtained using the STEAM sequence with parameters of TR=5 sec and TE=15 msec by a
      1.5-tesla clinical MRI system. We analyzed the concentrations of N
      acetylaspartate (NAA), creatine/phosphocreatine (Cr), and choline-containing
      compounds (Cho) using LCModel (Ver. 6.1). The concentrations of NAA in the left
      amygdala and the bilateral OFC in autistic patients were significantly decreased
      compared to those in the control group. In the autistic patients, the NAA
      concentrations in these regions correlated with their social quotient. These
      findings suggest the presence of neuronal dysfunction in the amygdala and OFC in
      autism. Dysfunction in the amygdala and OFC may contribute to the pathogenesis of
      autism.

PMID- 23114055
TI  - Hypofractionated helical intensity-modulated radiotherapy of the prostate bed
      after prostatectomy with or without the pelvic lymph nodes - the PRIAMOS trial.
AB  - BACKGROUND: While evidence on safety and efficacy of primary hypofractionated
      radiotherapy in prostate cancer is accumulating, data on postoperative
      hypofractionated treatment of the prostate bed and of the pelvic lymph nodes is
      still scarce. This phase II trial was initiated to investigate safety and
      feasibility of hypofractionated treatment of the prostate bed alone or with the
      pelvic lymph nodes. METHODS/DESIGN: A total of 80 prostate cancer patients with
      the indication for adjuvant radiotherapy will be enrolled, where 40 patients with
      a low risk of lymph node involvement (arm 1) and another 40 patients with a high
      risk of lymph node involvement (arm 2) will each receive 54 Gy in 18 fractions to
      the prostate bed. Arm 2 will be given 45 Gy to the pelvic lymph nodes
      additionally. Helical Tomotherapy and daily image guidance will be used.
      DISCUSSION: This trial was initiated to substantiate data on hypofractionated
      treatment of the prostate bed and generate first data on adjuvant
      hypofractionated radiotherapy of the pelvic lymph nodes. TRIAL REGISTRATION:
      ClinicalTrials.gov; NCT01620710.

PMID- 23114056
TI  - G * E interaction and neurodevelopment II. Focus on adversities in paediatric
      depression: the moderating role of serotonin transporter.
AB  - In a short series of articles, we will review the evidence for genotype by
      environment interaction (G * E) in developmental psychopathology. We will focus
      specifically on the characteristics of types of exposure assessed with respect to
      both their methods and findings. This article aims to review the studies
      exploring the moderating role of serotonin transporter on the effect of
      environmental adversities over time, particularly during childhood and
      adolescence, which is when level of internalizing symptoms and prevalence of mood
      disorders change substantially. Environmental adversities will not include abuse
      and maltreatment that have been reviewed before (see Bellani et al. 2012) and
      child's broader social ecology that will be reviewed in the next section.

PMID- 23114057
TI  - Force-dependent cell signaling in stem cell differentiation.
AB  - Stem cells interact with biochemical and biophysical signals in their
      extracellular environment. The biophysical signals are transduced to the stem
      cells either through the underlying extracellular matrix or externally applied
      forces. Increasing evidence has shown that these biophysical cues such as
      substrate stiffness and topography can direct stem cell differentiation and
      determine the cell fate. The mechanism of the biophysically induced
      differentiation is not understood; however, several key signaling components have
      been demonstrated to be involved in the force-mediated differentiation. This
      review will focus on focal adhesions, cytoskeletal contractility, Rho GTPase
      signaling and nuclear regulation in connection with biophysically induced
      differentiation. We will briefly introduce the important components of the
      mechanotransduction machinery, and the recent developments in the study of force
      dependent stem cell differentiation. 

PMID- 23114058
TI  - Encapsulation of gold nanoparticles into self-assembling protein nanoparticles.
AB  - BACKGROUND: Gold nanoparticles are useful tools for biological applications due
      to their attractive physical and chemical properties. Their applications can be
      further expanded when they are functionalized with biological molecules. The
      biological molecules not only provide the interfaces for interactions between
      nanoparticles and biological environment, but also contribute their biological
      functions to the nanoparticles. Therefore, we used self-assembling protein
      nanoparticles (SAPNs) to encapsulate gold nanoparticles. The protein
      nanoparticles are formed upon self-assembly of a protein chain that is composed
      of a pentameric coiled-coil domain at the N-terminus and trimeric coiled-coil
      domain at the C-terminus. The self-assembling protein nanoparticles form a
      central cavity of about 10 nm in size, which is ideal for the encapsulation of
      gold nanoparticles with similar sizes. RESULTS: We have used SAPNs to encapsulate
      several commercially available gold nanoparticles. The hydrodynamic size and the
      surface coating of gold nanoparticles are two important factors influencing
      successful encapsulation by the SAPNs. Gold nanoparticles with a hydrodynamic
      size of less than 15 nm can successfully be encapsulated. Gold nanoparticles with
      citrate coating appear to have stronger interactions with the proteins, which can
      interfere with the formation of regular protein nanoparticles. Upon encapsulation
      gold nanoparticles with polymer coating interfere less strongly with the ability
      of the SAPNs to assemble into nanoparticles. Although the central cavity of the
      SAPNs carries an overall charge, the electrostatic interaction appears to be less
      critical for the efficient encapsulation of gold nanoparticles into the protein
      nanoparticles. CONCLUSIONS: The SAPNs can be used to encapsulate gold
      nanoparticles. The SAPNs can be further functionalized by engineering functional
      peptides or proteins to either their N- or C-termini. Therefore encapsulation of
      gold nanoparticles into SAPNs can provide a useful platform to generate a
      multifunctional biodevices.

PMID- 23114060
TI  - Effects of pre-hospital clopidogrel administration on early and late residual
      platelet reactivity in ST-segment elevation myocardial infarction patients
      undergoing primary intervention.

PMID- 23114059
TI  - Identification of essential genes of the periodontal pathogen Porphyromonas
      gingivalis.
AB  - BACKGROUND: Porphyromonas gingivalis is a Gram-negative anaerobic bacterium
      associated with periodontal disease onset and progression. Genetic tools for the
      manipulation of bacterial genomes allow for in-depth mechanistic studies of
      metabolism, physiology, interspecies and host-pathogen interactions. Analysis of
      the essential genes, protein-coding sequences necessary for survival of P.
      gingivalis by transposon mutagenesis has not previously been attempted due to the
      limitations of available transposon systems for the organism. We adapted a
      Mariner transposon system for mutagenesis of P. gingivalis and created an
      insertion mutant library. By analyzing the location of insertions using massively
      parallel sequencing technology we used this mutant library to define genes
      essential for P. gingivalis survival under in vitro conditions. RESULTS: In
      mutagenesis experiments we identified 463 genes in P. gingivalis strain ATCC
      33277 that are putatively essential for viability in vitro. Comparing the 463 P.
      gingivalis essential genes with previous essential gene studies, 364 of the 463
      are homologues to essential genes in other species; 339 are shared with more than
      one other species. Twenty-five genes are known to be essential in P. gingivalis
      and B. thetaiotaomicron only. Significant enrichment of essential genes within
      Cluster of Orthologous Groups 'D' (cell division), 'I' (lipid transport and
      metabolism) and 'J' (translation/ribosome) were identified. Previously, the P.
      gingivalis core genome was shown to encode 1,476 proteins out of a possible
      1,909; 434 of 463 essential genes are contained within the core genome. Thus, for
      the species P. gingivalis twenty-two, seventy-seven and twenty-three percent of
      the genome respectively are devoted to essential, core and accessory functions.
      CONCLUSIONS: A Mariner transposon system can be adapted to create mutant
      libraries in P. gingivalis amenable to analysis by next-generation sequencing
      technologies. In silico analysis of genes essential for in vitro growth
      demonstrates that although the majority are homologous across bacterial species
      as a whole, species and strain-specific subsets are apparent. Understanding the
      putative essential genes of P. gingivalis will provide insights into metabolic
      pathways and niche adaptations as well as clinical therapeutic strategies.

PMID- 23114061
TI  - Risk of invasive pneumococcal disease varies by neighbourhood characteristics:
      implications for prevention policies.
AB  - This study investigates neighbourhood variation in rates of pneumococcal
      bacteraemia and community-level factors associated with neighbourhood
      heterogeneity in disease risk. We analysed data from 1416 adult and paediatric
      cases of pneumococcal bacteraemia collected during 2005-2008 from a population
      based hospital surveillance network in metropolitan Philadelphia. Cases were
      geocoded using residential address to measure disease incidence by neighbourhood
      and identify potential neighbourhood-level risk factors. Overall incidence of
      pneumococcal bacteraemia was 36?8 cases/100,000 population and varied
      significantly (0-67?8 cases/100,000 population) in 281 neighbourhoods. Increased
      disease incidence was associated with higher population density [incidence rate
      ratio (IRR) 1?10/10,000 people per mile2, 95% confidence interval (CI) 1?0-1?19],
      higher percent black population (per 10% increase) (IRR 1?07, 95% CI 1?04-1?09),
      population aged <=5 years (IRR 3?49, CI 1?8-5?18) and population aged >=65 years
      (IRR 1?19, CI 1?00-1?38). After adjusting for these characteristics, there was no
      significant difference in neighbourhood disease rates. This study demonstrates
      substantial small-area variation in pneumococcal bacteraemia risk that appears to
      be explained by neighbourhood sociodemographic characteristics. Identifying
      neighbourhoods with increased disease risk may provide valuable information to
      optimize implementation of prevention strategies.

PMID- 23114062
TI  - Prolonged outbreak of Serratia marcescens in Tartu University Hospital: a case
      control study.
AB  - BACKGROUND: The aim of our study was to investigate and control an outbreak and
      identify risk factors for colonization and infection with Serratia marcescens in
      two departments in Tartu University Hospital. METHODS: The retrospective case
      control study was conducted from July 2005 to December 2006. Molecular typing by
      pulsed field gel electrophoresis was used to confirm the relatedness of Serratia
      marcescens strains. Samples from the environment and from the hands of personnel
      were cultured. RESULTS: The outbreak involved 210 patients, 61 (29%) developed an
      infection, among them 16 were invasive infections. Multivariate analysis
      identified gestational age, arterial catheter use and antibiotic treatment as
      independent risk factors for colonization and infection with Serratia marcescens.
      Molecular typing was performed on 83 Serratia marcescens strains, 81 of them were
      identical and 2 strains were different. CONCLUSIONS: Given the occasionally
      severe consequences of Serratia marcescens in infants, early implementation of
      aggressive infection control measures involving patients and mothers as well as
      the personnel is of utmost importance.

PMID- 23114063
TI  - Acetazolamide for the prophylaxis of acute mountain sickness.

PMID- 23114064
TI  - Too much medicine, not enough mirth.

PMID- 23114065
TI  - Authors' reply to Jameson and Breusch.

PMID- 23114066
TI  - Authors' reply to National Joint Registry.

PMID- 23114067
TI  - Age restrictions on rotavirus vaccination cost lives.

PMID- 23114070
TI  - How the Liverpool care pathway has transformed end of life care.

PMID- 23114071
TI  - Healthcare and weather services must work together to limit risks of air
      pollution and high temperatures.

PMID- 23114072
TI  - Boys are entering puberty earlier, large study shows.

PMID- 23114073
TI  - Health campaigners question whether fall in maternal mortality in India is a
      result of more hospital deliveries.

PMID- 23114075
TI  - Changes to the GP contract threaten general practice in the UK.

PMID- 23114076
TI  - Breaking good news.

PMID- 23114077
TI  - Emergency hospital evacuation as Hurricane Sandy hits New York.

PMID- 23114078
TI  - From taxonomic literature to cybertaxonomic content.

PMID- 23114079
TI  - National inventory of emergency departments in Singapore.
AB  - BACKGROUND: Emergency departments (EDs) are the basic units of emergency care.
      We performed a national inventory of all Singapore EDs and describe their
      characteristics and capabilities. METHODS: Singapore EDs accessible to the
      general public 24/7 were surveyed using the National ED Inventories instrument (
      http://www.emnet-nedi.org). ED staff members were asked about ED characteristics
      with reference to calendar year 2007. RESULTS: Fourteen EDs participated (100%
      response). All EDs were located in hospitals, and most (92%) were independent
      departments. One was a psychiatric ED; the rest were general EDs. Among general
      EDs, all had a contiguous layout, with medical and surgical care provided in one
      area. All but two EDs saw both adults and children; one ED was adult-only, and
      the other saw only children. Six were in the public sector and seven in private
      health-care institutions, with public EDs seeing the majority (78%) of ED
      patients. Each private ED had an annual patient census of <30,000. These EDs
      received 2% of ambulances and had an inpatient admission rate of 7%. Each public
      ED had an annual census of >60,000. They received 98% of ambulances and had an
      inpatient admission rate of 30%. Two public EDs reported being overcapacity; no
      private EDs did. For both public and private EDs, availability of consultant
      resources in EDs was high, while technological resources varied. CONCLUSION:
      Characteristics and capabilities of Singapore EDs varied and were largely
      dependent on whether they are in public or private hospitals. This initial
      inventory establishes a benchmark to further monitor the development of emergency
      care in Singapore.

PMID- 23114080
TI  - Advanced rheological characterization of soft colloidal model systems.
AB  - The complex flow behavior of polymer-based soft colloidal model systems was
      investigated using steady and oscillatory shear to prove new concepts for
      advanced rheological characterization. In the very dilute regime we investigated
      high molecular weight polybutadiene star polymers to quantify the internal
      relaxation time arising from the polymeric nature of these ultra-soft colloids.
      The observed shear-induced brush deformation is interpreted in terms of the
      internal Zimm time tau(z). The observed dependence of tau(z) on matrix viscosity
      can be explained by shrinkage of the star polymer due to an increasing
      incompatibility with increasing matrix molecular weight. The influence of the
      polymeric nature on the characteristic structural relaxation time in the
      concentrated regime was investigated using non-linear rheology following Wyss et
      al (SRFS) (2007 Phys. Rev. Lett. 98 238303). Here we used star-like block
      copolymer micelles to systematically tune the 'softness' of the colloids by
      variation of the block ratio. A master curve with proper scaling parameters could
      be generated independent of the degree of colloidal 'softness'. However, the
      obtained strain-rate independent structural relaxation time tau(0) was not
      observed in the linear regime. In addition, a high frequency discrepancy was
      clearly found in all our experimental data. Both reflect the shortcomings of the
      SRFS approach.

PMID- 23114082
TI  - Can we predict the evolution of an unpredictable disease like multiple sclerosis?

PMID- 23114081
TI  - Lovastatin for adult patients with dengue: protocol for a randomised controlled
      trial.
AB  - BACKGROUND: Dengue is the most important vector-borne viral infection of man,
      with approximately 2 billion people living in areas at risk. Infection results in
      a range of manifestations from asymptomatic infection through to life-threatening
      shock and haemorrhage. One of the hallmarks of severe dengue is vascular
      endothelial disruption. There is currently no specific therapy and clinical
      management is limited to supportive care. Statins are a class of drug initially
      developed for lipid lowering. There has been considerable recent interest in
      their effects beyond lipid lowering. These include anti-inflammatory effects at
      the endothelium. In addition, it is possible that lovastatin may have an anti
      viral effect against dengue. Observational data suggest that the use of statins
      may improve outcomes for such conditions as sepsis and pneumonia. This paper
      describes the protocol for a randomised controlled trial investigating a short
      course of lovastatin therapy in adult patients with dengue. METHODS/DESIGN: A
      randomised, double-blind, placebo-controlled trial will investigate the effects
      of lovastatin therapy in the treatment of dengue. The trial will be conducted in
      two phases with an escalation of dose between phases if an interim safety review
      is satisfactory. This is an exploratory study focusing on safety and there are no
      data on which to base a sample size calculation. A target sample size of 300
      patients in the second phase, enrolled over two dengue seasons, was chosen based
      on clinical judgement and feasibility considerations. In a previous randomised
      trial in dengue, about 10% and 30% of patients experienced at least one serious
      adverse event or adverse event, respectively. With 300 patients, we will have 80%
      power to detect an increase of 12% (from 10% to 22%) or 16% (from 30% to 46%) in
      the frequency of adverse events. Furthermore, this sample size ensures some power
      to explore the efficacy of statins. DISCUSSION: The development of a dengue
      therapeutic that can attenuate disease would be an enormous advance in global
      health. The favourable effects of statins on the endothelium, their good safety
      profile and their low cost make lovastatin an attractive therapeutic candidate.
      TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number
      ISRCTN03147572.

PMID- 23114083
TI  - Treatment of severe pemphigus vulgaris of the scalp with adjuvant rituximab and
      immunoadsorption.

PMID- 23114085
TI  - Managing esophageal fistulae by endoscopic transluminal drainage in esophageal
      cancer patients with superior mediastinal sepsis after esophagectomy.
AB  - The management of postoperative leaks into the mediastinum after esophagectomy
      remains a challenge. We describe our clinical management of this complication
      through endoscopic transluminal drainage. Between 2008 and 2011, 4 patients with
      esophageal squamous cell carcinoma (ESCC) who underwent McKeown-type
      esophagectomy with two-field lymphadenectomy experienced complicated anastomotic
      fistulae in the presence of superior mediastinal sepsis. All 4 patients underwent
      endoscopic transluminal drainage, and all survived. The mean healing period was
      50 days (range, 31 to 58 days), the mean stay in the intensive care unit was 7.3
      days (range, 1 to 18 days), and the mean hospital stay was 64.5 days (range, 49
      to 70 days). Endoscopically guided transluminal drainage should be considered for
      ESCC patients with superior mediastinal fistulae after esophagectomy.

PMID- 23114084
TI  - Clinical impact of copy number variation analysis using high-resolution
      microarray technologies: advantages, limitations and concerns.
AB  - Copy number variation (CNV) analysis has had a major impact on the field of
      medical genetics, providing a mechanism to identify disease-causing genomic
      alterations in an unprecedented number of diseases and phenotypes. CNV analysis
      is now routinely used in the clinical diagnostic laboratory, and has led to a
      significant increase in the detection of chromosomal abnormalities. These
      findings are used for prenatal decision making, clinical management and genetic
      counseling. Although a powerful tool to identify genomic alterations, CNV
      analysis may also result in the detection of genomic alterations that have
      unknown clinical significance or reveal unintended information. This highlights
      the importance of informed consent and genetic counseling for clinical CNV
      analysis. This review examines the advantages and limitations of CNV discovery in
      the clinical diagnostic laboratory, as well as the impact on the clinician and
      family. 

PMID- 23114086
TI  - The cellular decision between apoptosis and autophagy.
AB  - Apoptosis and autophagy are important molecular processes that maintain
      organismal and cellular homeostasis, respectively. While apoptosis fulfills its
      role through dismantling damaged or unwanted cells, autophagy maintains cellular
      homeostasis through recycling selective intracellular organelles and molecules.
      Yet in some conditions, autophagy can lead to cell death. Apoptosis and autophagy
      can be stimulated by the same stresses. Emerging evidence indicates an interplay
      between the core proteins in both pathways, which underlies the molecular
      mechanism of the crosstalk between apoptosis and autophagy. This review
      summarizes recent literature on molecules that regulate both the apoptotic and
      autophagic processes.

PMID- 23114087
TI  - The 2002 AJCC TNM classification is a better predictor of primary small cell
      esophageal carcinoma outcome than the VALSG staging system.
AB  - Small cell carcinoma of the esophagus (SCCE) is a rare and aggressive malignant
      tumor with a poor prognosis. The optimal disease staging system and treatment
      approaches have not yet been defined. This study aimed to evaluate the prediction
      of different staging systems for prognosis and treatment options of SCCE. We
      retrospectively accessed the clinicopathologic characteristics, treatment
      strategy, and prognosis of 76 patients diagnosed with primary SCCE between 2001
      and 2011. The 1-, 2-, 3-, and 5-year overall survival rates were 58%, 31%, 19%,
      and 13%, respectively. Univariate analysis showed that the 2002 American Joint
      Committee on Cancer (AJCC) tumor-node-metastasis (TNM) classification (P =
      0.002), Veterans Administration Lung Study Group (VALSG) stage (P = 0.001),
      predisposing factors (P < 0.001), T category (P = 0.023), and M category (P <
      0.001) were prognostic factors for overall survival. Multivariate analysis showed
      that the 2002 AJCC TNM stage (P < 0.001) was the only independent prognostic
      factor for survival. The value of the area under the receiver operator
      characteristic (ROC) curve (AUC) of the 2002 AJCC TNM staging system was larger
      than that of VALSG staging system with regard to predicting overall survival
      (0.774 vs. 0.620). None of the single treatment regimens showed any benefit for
      survival by Cox regression analysis. Thus, the 2002 AJCC TMN staging system
      improved the prediction of SCCE prognosis; however, the optimal treatment regimen
      for SCCE remains unclear.

PMID- 23114088
TI  - SPARC expression and prognostic value in non-small cell lung cancer.
AB  - Secreted protein, acidic and rich in cysteine (SPARC) is expressed in numerous
      types of tumors and is suggested to have prognostic value. Moreover, because of
      its strong affinity for albumin, and hence albumin-bound drugs, SPARC has
      increasingly become a focus for research. In this study, we aimed to determine
      SPARC expression in patients with non-small cell lung cancer (NSCLC) and
      investigate the association of SPARC with disease prognosis. Tissue microarrays
      were constructed with specimens from 105 patients with NSCLC treated at Sun Yat
      sen University Cancer Center, and immunohistochemical analysis was performed on
      these tissue microarrays to assess SPARC expression. Our results showed that
      SPARC expression status did not significantly relate with age, gender, and tumor
      stage. However, SPARC was expressed more frequently in squamous cell carcinoma
      than in adenocarcinoma (75% vs. 43.5%, P = 0.004). Patients with smoking history
      had higher SPARC expression than non-smokers (68.2% vs. 33.3%, P = 0.002). In
      both univariate and multivariate analyses, SPARC was a prognostic factor of
      overall survival (HR = 0.32; 95% CI: 0.16-0.65) but not disease-free survival.
      Our study indicates that SPARC expression is higher in squamous cell carcinoma
      than in adenocarcinoma in NSCLC. Most notably, SPARC can be used as a prognostic
      factor for NSCLC.

PMID- 23114089
TI  - The role of stem cells in airway repair: implications for the origins of lung
      cancer.
AB  - Lung cancer is the leading cause of cancer-related deaths worldwide. Recently,
      advancements in our ability to identify and study stem cell populations in the
      lung have helped researchers to elucidate the central role that cells with stem
      cell-like properties may have in lung tumorigenesis. Much of this research has
      focused on the use of the airway repair model to study response to injury. In
      this review, we discuss the primary evidence of the role that cancer stem cells
      play in lung cancer development. The implications of a stem cell origin of lung
      cancer are reviewed, and the importance of ongoing research to identify novel
      therapeutic and prognostic targets is reiterated.

PMID- 23114090
TI  - Repressing malic enzyme 1 redirects glucose metabolism, unbalances the redox
      state, and attenuates migratory and invasive abilities in nasopharyngeal
      carcinoma cell lines.
AB  - A large amount of nicotinamide adenine dinucleotide phosphate (NADPH) is required
      for fatty acid synthesis and maintenance of the redox state in cancer cells.
      Malic enzyme 1(ME1)-dependent NADPH production is one of the three pathways that
      contribute to the formation of the cytosolic NADPH pool. ME1 is generally
      considered to be overexpressed in cancer cells to meet the high demand for
      increased de novo fatty acid synthesis. In the present study, we found that
      glucose induced higher ME1 activity and that repressing ME1 had a profound impact
      on glucose metabolism of nasopharyngeal carcinoma(NPC) cells. High incorporation
      of glucose and an enhancement of the pentose phosphate pathway were observed in
      ME1-repressed cells. However, there were no obvious changes in the other two
      pathways for glucose metabolism: glycolysis and oxidative phosphorylation.
      Interestingly, NADPH was decreased under low-glucose condition in ME1-repressed
      cells relative to wild-type cells, whereas no significant difference was observed
      under high-glucose condition. ME1-repressed cells had significantly decreased
      tolerance to low-glucose condition. Moreover, NADPH produced by ME1 was not only
      important for fatty acid synthesis but also essential for maintenance of the
      intracellular redox state and the protection of cells from oxidative stress.
      Furthermore, diminished migration and invasion were observed in ME1-repressed
      cells due to a reduced level of Snail protein. Collectively, these results
      suggest an essential role for ME1 in the production of cytosolic NADPH and
      maintenance of migratory and invasive abilities of NPC cells.

PMID- 23114091
TI  - The effect of obesity on polycystic ovary syndrome: a systematic review and meta
      analysis.
AB  - While many women with polycystic ovary syndrome (PCOS) are overweight, obese or
      centrally obese, the effect of excess weight on the outcomes of PCOS is
      inconsistent. The review aimed to assess the effects of overweight, obesity and
      central obesity on the reproductive, metabolic and psychological features of
      PCOS. MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials
      (CENTRAL) and PSYCINFO were searched for studies reporting outcomes according to
      body mass index categories or body fat distribution. Data were presented as mean
      difference or risk ratio (95% confidence interval). This review included 30
      eligible studies. Overweight or obese women with PCOS had decreased sex hormone
      binding globulin (SHBG), increased total testosterone, free androgen index,
      hirsutism, fasting glucose, fasting insulin, homeostatic model assessment-insulin
      resistance index and worsened lipid profile. Obesity significantly worsened all
      metabolic and reproductive outcomes measured except for hirsutism when compared
      to normal weight women with PCOS. Overweight women had no differences in total
      testosterone, hirsutism, total-cholesterol and low-density lipoprotein
      cholesterol compared to normal weight women and no differences in SHBG and total
      testosterone compared to obese women. Central obesity was associated with higher
      fasting insulin levels. These results suggest that prevention and treatment of
      obesity is important for the management of PCOS.

PMID- 23114092
TI  - Reliability and group differences in quantitative cervicothoracic measures among
      individuals with and without chronic neck pain.
AB  - BACKGROUND: Clinicians frequently rely on subjective categorization of
      impairments in mobility, strength, and endurance for clinical decision-making;
      however, these assessments are often unreliable and lack sensitivity to change.
      The objective of this study was to determine the inter-rater reliability, minimum
      detectable change (MDC), and group differences in quantitative cervicothoracic
      measures for individuals with and without chronic neck pain (NP). METHODS:
      Nineteen individuals with NP and 20 healthy controls participated in this case
      control study. Two physical therapists performed a 30-minute examination on
      separate days. A handheld dynamometer, gravity inclinometer, ruler, and stopwatch
      were used to quantify cervical range of motion (ROM), cervical muscle strength
      and endurance, and scapulothoracic muscle length and strength, respectively.
      RESULTS: Intraclass correlation coefficients for inter-rater reliability were
      significantly greater than zero for most impairment measures, with point
      estimates ranging from 0.45 to 0.93. The NP group exhibited reduced cervical ROM
      (P <= 0.012) and muscle strength (P <= 0.038) in most movement directions,
      reduced cervical extensor endurance (P = 0.029), and reduced rhomboid and middle
      trapezius muscle strength (P <= 0.049). CONCLUSIONS: Results demonstrate the
      feasibility of obtaining objective cervicothoracic impairment measures with
      acceptable inter-rater agreement across time. The clinical utility of these
      measures is supported by evidence of impaired mobility, strength, and endurance
      among patients with NP, with corresponding MDC values that can help establish
      benchmarks for clinically significant change.

PMID- 23114093
TI  - Rounding rituximab dose to nearest vial size.
AB  - PURPOSE: To determine the feasibility of dose-rounding rituximab by looking at
      the potential deviation from the prescribed dose to the dose rounded to the
      nearest vial size. METHODS: This study is a retrospective chart review of all
      rituximab orders prescribed for hematologic or oncologic indications over a
      period of 24 months. The feasibility of dose-rounding rituximab to the nearest
      vial size was evaluated by looking at the potential deviation of the prescribed
      dose to the rounded dose. Physician opinion towards dose rounding rituximab was
      assessed through a survey. RESULTS: From October 2008 through September 2010,
      2028 orders of rituximab were prescribed and processed. Ninety-nine percent of
      all rituximab doses fell within 10% dose deviation if rounded to the nearest 100
      mg vial size and 66.1% of all rituximab orders fell within 5% dose deviation. All
      responding physicians were comfortable with at least a 5% dose deviation,
      projecting a yearly savings of approximately US$37,000 through rounding down and
      capturing additional cost of approximately US$43,000 through rounding up.
      CONCLUSION: The projected savings of dose-rounding rituximab to the nearest vial
      size resulted in both substantial financial savings and reduced unnecessary
      wastage of unused drug.

PMID- 23114094
TI  - Differentiating rapid- and slow-growing mycobacteria by difference in time to
      growth detection in liquid media.
AB  - Nontuberculous mycobacteria (NTM) are classified into 2 categories: slow-growing
      mycobacteria (SGM) and rapid-growing mycobacteria (RGM), based on interval to
      colony formation by subculture on solid media. However, little is known about the
      growth rate of NTM in liquid broth media. We evaluated the differences in time to
      growth detection (TGD) of RGM and SGM in liquid broth media according to acid
      fast stain. Among the 696 NTM isolates, 201 were RGM and 495 were SGM. In acid
      fast bacilli (AFB)-negative specimens, the mean TGD was 133 h for RGM and 269 h
      for SGM (P < 0.001). In AFB-positive specimens, the mean TGD was 112 +/- 37 h for
      RGM and 155 +/- 125 h for SGM (P = 0.063). In the AFB-negative group, a cut-off
      value of 6 days was most effective for distinguishing SGM from RGM; however, in
      the AFB-positive group, an appropriate cut-off value was hard to define with TGD
      only.

PMID- 23114095
TI  - The nature of the laning transition in two dimensions.
AB  - If a binary colloidal mixture is oppositely driven by an external field, a
      transition towards a laned state occurs at sufficiently large drives, where
      particles driven alike form elongated structures ('lanes') characterized by a
      large correlation length xi along the drive. Here we perform extensive Brownian
      dynamics computer simulations on a two-dimensional equimolar binary Yukawa system
      driven by a constant force that acts oppositely on the two species. We
      systematically address finite-size effects on lane formation by exploring large
      systems up to 262,144 particles under various boundary conditions. It is found
      that the correlation length xi along the field depends exponentially on the
      driving force (or Peclet number). Conversely, in a finite system, xi reaches a
      fraction of the system size at a driving force which is logarithmic in the system
      size, implying massive finite-size corrections. For a fixed finite drive, xi does
      not diverge in the thermodynamic limit. Therefore, though laning has a signature
      as a sharp transition in a finite system, it is a smooth crossover in the
      thermodynamic limit.

PMID- 23114096
TI  - Dynamics of branched tissue assembly.
AB  - The assembly of cells into tissues is a complex process controlled by numerous
      signaling pathways to ensure the fidelity of the final structure. Tissue assembly
      is also very dynamic, as exemplified by the formation of branched organs. Here we
      present two examples of tissue assembly in branched systems that highlight this
      dynamic nature: formation of the tracheal network in Drosophila melanogaster and
      the ducts of the mammary gland in mice. Extension of the branches during tracheal
      development is a stereotyped process that produces identical organ geometries
      across individuals, whereas elongation of the ducts of the pubertal mammary gland
      is a non-stereotyped process that produces unique patterns. By studying these two
      organs, we can begin to understand the dynamic nature of development of other
      stereotyped and non-stereotyped branching systems, including the lung, kidney,
      and salivary gland. 

PMID- 23114097
TI  - The endocrine stress response is linked to one specific locus on chromosome 3 in
      a mouse model based on extremes in trait anxiety.
AB  - BACKGROUND: The hypothalamic-pituitary-adrenal (HPA) axis is essential to control
      physiological stress responses in mammals. Its dysfunction is related to several
      mental disorders, including anxiety and depression. The aim of this study was to
      identify genetic loci underlying the endocrine regulation of the HPA axis.
      METHOD: High (HAB) and low (LAB) anxiety-related behaviour mice were established
      by selective inbreeding of outbred CD-1 mice to model extremes in trait anxiety.
      Additionally, HAB vs. LAB mice exhibit comorbid characteristics including a
      differential corticosterone response upon stress exposure. We crossbred HAB and
      LAB lines to create F1 and F2 offspring. To identify the contribution of the
      endocrine phenotypes to the total phenotypic variance, we examined multiple
      behavioural paradigms together with corticosterone secretion-based phenotypes in
      F2 mice by principal component analysis. Further, to pinpoint the genomic loci of
      the quantitative trait of the HPA axis stress response, we conducted genome-wide
      multipoint oligogenic linkage analyses based on Bayesian Markov chain Monte Carlo
      approach as well as parametric linkage in three-generation pedigrees, followed by
      a two-dimensional scan for epistasis and association analysis in freely
      segregating F2 mice using 267 single-nucleotide polymorphisms (SNPs), which were
      identified to consistently differ between HAB and LAB mice as genetic markers.
      RESULTS: HPA axis reactivity measurements and behavioural phenotypes were
      represented by independent principal components and demonstrated no correlation.
      Based on this finding, we identified one single quantitative trait locus (QTL) on
      chromosome 3 showing a very strong evidence for linkage (2ln (L-score) > 10, LOD
      > 23) and significant association (lowest Bonferroni adjusted p < 10-28) to the
      neuroendocrine stress response. The location of the linkage peak was estimated at
      42.3 cM (95% confidence interval: 41.3 - 43.3 cM) and was shown to be in
      epistasis (p-adjusted < 0.004) with the locus at 35.3 cM on the same chromosome.
      The QTL harbours genes involved in steroid synthesis and cardiovascular effects.
      CONCLUSION: The very prominent effect on stress-induced corticosterone secretion
      of the genomic locus on chromosome 3 and its involvement in epistasis highlights
      the critical role of this specific locus in the regulation of the HPA axis.

PMID- 23114098
TI  - Gestational age at birth and morbidity, mortality, and growth in the first 4
      years of life: findings from three birth cohorts in Southern Brazil.
AB  - BACKGROUND: We assessed anthropometric status, breastfeeding duration, morbidity,
      and mortality outcomes during the first four years of life according to
      gestational age, in three population-based birth cohorts in the city of Pelotas,
      Southern Brazil. METHODS: Total breastfeeding duration, neonatal mortality,
      infant morbidity and mortality, and anthropometric measures taken at 12 and 48
      months were evaluated in children of different gestational ages born in 1982,
      1993 and 2004 in Southern Brazil. RESULTS: Babies born <34 weeks of gestation and
      those born between 34-36 weeks presented increased morbidity and mortality, were
      breastfed for shorter periods, and were more likely to be undernourished at 12
      months of life, in comparison with the 39-41 weeks group. Children born with 37
      weeks were more than twice as likely to die in the first year of life, and were
      also at increased risk of hospitalization and underweight at 12 months of life.
      Post-term infants presented an increased risk of neonatal mortality. CONCLUSION:
      The increased risks of morbidity and mortality among preterm (<37 weeks of
      gestation) and post-term (>41 weeks) are well known. In our population babies
      born at 37 also present increased risk. As the proportion of preterm and early
      term babies has increased markedly in recent years, this is a cause for great
      concern.

PMID- 23114099
TI  - Prevalence and correlates of Kaposi's sarcoma-associated herpesvirus infection in
      a sample of men who have sex with men in Eastern China.
AB  - This study aimed to determine the seroprevalence of Kaposi's sarcoma-associated
      herpesvirus(KSHV) and related factors in men who have sex with men (MSM) in
      China. A total of 208 subjects were recruited from eastern China from 2008 to
      2009. Plasma samples were collected and screened for KSHV, HIV and syphilis.
      Overall, KSHV seroprevalence was 32.7% in the subjects. About 92.7% of subjects
      reported having ever had anal sex with a man, of whom 67.8% had receptive anal
      sex and 77.9% had insertive anal sex. About 93.1% of the study participants
      reported having had oral sex with a man, of whom 76.0% had receptive oral sex and
      56.7% had insertive oral sex. KSHV seropositivity was independently associated
      with receptive anal sex[odds ratio (OR) 2.68, 95% confidence interval (CI) 1.15
      6.23], syphilis (OR 3.25, 95% CI1.56-6.76) and HSV-2 infection (OR 2.40, 95% CI
      1.09-5.26). KSHV infection is highly prevalent and is probably sexually
      transmitted among MSM in eastern China.

PMID- 23114100
TI  - Mining the literature: new methods to exploit keyword profiles.
AB  - Bibliographic records in the PubMed database of biomedical literature are
      annotated with Medical Subject Headings (MeSH) by curators, which summarize the
      content of the articles. Two recent publications explain how to generate profiles
      of MeSH terms for a set of bibliographic records and to use them to define any
      given concept by its associated literature. These concepts can then be related by
      their keyword profiles, and this can be used, for example, to detect new
      associations between genes and inherited diseases. SEE RELATED RESEARCH ARTICLES:
      http://www.biomedcentral.com/1471
      2105/13/249/abstracthttp://genomemedicine.com/content/4/9/75/abstract.

PMID- 23114101
TI  - Permanent tattoos: evidence of pseudolymphoma in three patients and metal
      composition of the dyes.
AB  - Tattoo-induced pseudolymphoma is a cutaneous inflammatory response, the
      pathogenesis of which is still unknown. The objective of the present work was to
      find a possible causal relationship between pseudolymphomatous reactions on the
      red areas of tattoos and the metals contained in tattoo pigments and skin
      biopsies. Three individuals with cutaneous lesions on the red areas of tattoos
      were observed. Clinical and immunohistochemical examinations of the lesions were
      performed, and the concentrations of Cd, Co, Cr, Hg, Ni and Pb were measured in
      pigments and biopsy samples. Pseudolymphomas in the red areas were diagnosed in
      all three cases; one showed the prevalence of B-lymphocytes, whereas the other
      two showed a prevalence of T cells with a lichenoid pattern. Patch tests were
      negative. Corticosteroid therapy was ineffective. Cadmium, Co, Hg and Pb in the
      pigments were probably present as impurities, whereas Cr and Ni were the main
      components. Chromium and Ni had the highest concentrations, also in the biopsy
      samples. Permanent tattoos appear to be unsafe, considering the increasing number
      of diagnosed pseudolymphomas. It can be excluded that Hg was responsible for the
      reactions, given that the concentration in the red dyes and biopsies was very
      low. Significant levels of Cr and Ni should be considered as the causes of
      possible dermal reactions.

PMID- 23114102
TI  - A cohort description and analysis of the effect of gabapentin on idiopathic
      cough.
AB  - BACKGROUND: Chronic idiopathic cough (known as cough hypersensitivity syndrome)
      is defined by cough in the absence of an identifiable cause. Gabapentin has been
      suggested as a treatment but evidence is scarce. The aim of our study was to
      describe the clinical features of patients with unexplained chronic cough and to
      investigate the effect of gabapentin (600 mg twice a day for a minimal duration
      of 4 weeks) in reducing cough symptoms. METHODS: A patient cohort analysis was
      performed. Patients were retrieved using a query in our medical database for the
      words 'cough' and 'gabapentin' in 2011. Patients without a clear etiology of
      cough despite having performed a stepwise diagnostic approach, were included.
      Medical records of these patients were analyzed. A telephonic survey was
      performed and patients were asked to retrospectivally rate their cough when they
      attended the outpatient clinic. They were then asked to rate their cough after
      treatment with gabapentin. A scale from one to ten was used to score cough
      severity. They were also questioned about the triggers inducing cough. To
      evaluate the cough severity score, the results were correlated with questions of
      the Leicester Cough Questionnaire. RESULTS: We recruited 51 patients (87% female)
      with a mean age of onset of 47 years (+/- 14 y) and an average cough duration of
      48 months. The most frequently reported cough triggers included change of
      temperature (57%), talking (49%) and odours (45%). In 67% of patients, the urge
      to cough was located in the throat area. Thirty-five patients effectively took
      the prescribed gabapentin. The average improvement in cough score was 2.8/10
      (p<0.0001). Of the 35 patients, 20 achieved improvement of their cough symptoms.
      Responders had a higher pre-treatment cough severity score (p=0.02) and were more
      likely to have a history of pre-cough airway infection (p=0.04). Current cough
      severity score negatively correlated with the Leicester Cough Questionnaire
      scores (p=0.05). CONCLUSION: Chronic idiopathic cough were predominantly middle
      aged women, frequently reporting various cough triggers. We also demonstrated
      that gabapentin can significantly improve cough in these patients. Responders
      tend to have higher pre-treatment severity scores and have a history of an airway
      infection.

PMID- 23114103
TI  - Genetic analysis of the FUS/TLS gene in essential tremor.
AB  - BACKGROUND AND PURPOSE: Although essential tremor (ET) has a genetic basis,
      specific genes have not been identified. Recently, in a large ET family (FET1)
      from Quebec, a non-sense mutation (p.Q290X) in the amyotrophic lateral sclerosis
      (ALS) gene fused in sarcoma/translated in liposarcoma (FUS/TLS) was identified by
      exome sequencing. No confirmatory studies have been published. METHODS: Two
      hundred and fifty-nine ET cases and 262 controls were enrolled in a study at
      Columbia University. We performed a comprehensive analysis of the FUS/TLS gene by
      sequencing all exons in a subsample of 116 ET cases with early-onset (<=40 years)
      ET. We evaluated an association between ET and SNPs in the FUS/TLS gene by
      genotyping four haplotype tagging SNPs in all 259 ET cases and 262 controls.
      Additionally, seven variants associated with ALS, two variants of unknown
      pathogenicity detected in ALS cases, eight mis-sense variants predicted to be
      damaging, and six rare variants were genotyped in these 259 ET cases and 262
      controls. RESULTS: FUS/TLS mutations previously reported in ALS, the FET1 family,
      or novel mutations were not found in any of the 116 early-onset ET cases. In the
      case-control analyses, although the power of the performed associations was
      limited, no significant association between tagging SNPs in FUS/TLS and ET was
      observed, and none of the analyzed SNPs showed evidence of association with ET.
      CONCLUSION: Our study suggests that pathogenic mutations in FUS/TLS are rare in a
      sample of early-onset ET cases in North America. We did not find evidence that
      the FUS/TLS gene is a risk factor for ET.

PMID- 23114104
TI  - Growth patterns among HIV-exposed infants receiving nevirapine prophylaxis in
      Pune, India.
AB  - BACKGROUND: India has among the highest rates of infant malnutrition. Few studies
      investigating the growth patterns of HIV-exposed infants in India or the impact
      of timing of HIV infection on growth in settings such as India exist. METHODS: We
      used data from the Six Week Extended Nevirapine (SWEN) trial to compare the
      growth patterns of HIV-infected and HIV-exposed but uninfected infants accounting
      for timing of HIV infection, and to identify risk factors for stunting,
      underweight and wasting. Growth and timing of HIV infection were assessed at
      weeks 1, 2, 4, 6, 10, 14 weeks and 6, 9, 12 months of life. Random effects
      multivariable logistic regression method was used to assess factors associated
      with stunting, underweight and wasting. RESULTS: Among 737 HIV-exposed infants,
      93 (13%) were HIV-infected by 12 months of age. Among HIV-infected and uninfected
      infants, baseline prevalence of stunting (48% vs. 46%), underweight (27% vs. 26%)
      and wasting (7% vs. 11%) was similar (p>0.29), but by 12 months stunting and
      underweight, but not wasting, were significantly higher in HIV-infected infants
      (80% vs. 56%, 52% vs. 29%, p< 0.0001; 5% vs. 6%, p=0.65, respectively). These
      differences rapidly manifested within 4-6 weeks of birth. Infants infected in
      utero had the worst growth outcomes during the follow-up period. SWEN was
      associated with non-significant reductions in stunting and underweight among HIV
      infected infants and significantly less wasting in HIV-uninfected infants. In
      multivariate analysis, maternal CD4 < 250, infant HIV status, less breastfeeding,
      low birth weight, non-vaginal delivery, and infant gestational age were
      significant risk factors for underweight and stunting. CONCLUSION: Baseline
      stunting and underweight was high in both HIV-infected and uninfected infants;
      growth indices diverged early and were impacted by timing of infection and SWEN
      prophylaxis. Early growth monitoring of all HIV-exposed infants is an important
      low-cost strategy for improving health and survival outcomes of these infants.
      TRIAL REGISTRATION: NCT00061321.

PMID- 23114105
TI  - Modern psychometrics applied in rheumatology--a systematic review.
AB  - BACKGROUND: Although item response theory (IRT) appears to be increasingly used
      within health care research in general, a comprehensive overview of the frequency
      and characteristics of IRT analyses within the rheumatic field is lacking. An
      overview of the use and application of IRT in rheumatology to date may give
      insight into future research directions and highlight new possibilities for the
      improvement of outcome assessment in rheumatic conditions. Therefore, this study
      systematically reviewed the application of IRT to patient-reported and clinical
      outcome measures in rheumatology. METHODS: Literature searches in PubMed, Scopus
      and Web of Science resulted in 99 original English-language articles which used
      some form of IRT-based analysis of patient-reported or clinical outcome data in
      patients with a rheumatic condition. Both general study information and IRT
      specific information were assessed. RESULTS: Most studies used Rasch modeling for
      developing or evaluating new or existing patient-reported outcomes in rheumatoid
      arthritis or osteoarthritis patients. Outcomes of principle interest were
      physical functioning and quality of life. Since the last decade, IRT has also
      been applied to clinical measures more frequently. IRT was mostly used for
      evaluating model fit, unidimensionality and differential item functioning, the
      distribution of items and persons along the underlying scale, and reliability.
      Less frequently used IRT applications were the evaluation of local independence,
      the threshold ordering of items, and the measurement precision along the scale.
      CONCLUSION: IRT applications have markedly increased within rheumatology over the
      past decades. To date, IRT has primarily been applied to patient-reported
      outcomes, however, applications to clinical measures are gaining interest. Useful
      IRT applications not yet widely used within rheumatology include the cross
      calibration of instrument scores and the development of computerized adaptive
      tests which may reduce the measurement burden for both the patient and the
      clinician. Also, the measurement precision of outcome measures along the scale
      was only evaluated occasionally. Performed IRT analyses should be adequately
      explained, justified, and reported. A global consensus about uniform guidelines
      should be reached concerning the minimum number of assumptions which should be
      met and best ways of testing these assumptions, in order to stimulate the quality
      appraisal of performed IRT analyses.

PMID- 23114106
TI  - Cap'n'collar differentiates the mandible from the maxilla in the beetle Tribolium
      castaneum.
AB  - BACKGROUND: The biting mandible of the arthropods is thought to have evolved in
      the ancestor of the insects, crustaceans and myriapods: the Mandibulata. A unique
      origin suggests a common set of developmental genes will be required to pattern
      the mandible in different arthropods. To date we have functional studies on
      patterning of the mandibular segment of Drosophila melanogaster showing in
      particular the effects of the gene cap'n'collar (cnc), however, the dipteran head
      is far from representative of insects or of more distantly related mandibulates;
      Drosophila does not even possess a mandibular appendage. To study the development
      of a more representative insect mandible, we chose the red flour beetle Tribolium
      castaneum and investigated the function of the Tribolium orthologs of
      cap'n'collar (Tc-cnc) and the Hox gene Deformed (Tc-Dfd). In order to determine
      the function of Tc-cnc and Tc-Dfd, transcripts were knocked down by maternal RNA
      interference (RNAi). The effects of gene knockdown were examined in the
      developing embryos and larvae. The effect of Tc-cnc and Tc-Dfd knockdown on the
      expression of other genes was determined by using in situ hybridization on
      Tribolium embryos. RESULTS: Our analyses show that Tc-cnc is required for
      specification of the identity of the mandibular segment of Tribolium and
      differentiates the mandible from maxillary identity. Loss of Tc-cnc function
      results in a transformation of the mandible to maxillary identity as well as
      deletion of the labrum. Tc-Dfd and the Tribolium homolog of proboscipedia (Tc-mxp
      = maxillopedia), Hox genes that are required to pattern the maxillary appendage,
      are expressed in a maxilla-like manner in the transformed mandible. Tribolium
      homologs of paired (Tc-prd) and Distal-less (Tc-Dll) that are expressed in the
      endites and telopodites of embryonic appendages are also expressed in a maxilla
      like manner in the transformed mandible.We also show that Tc-Dfd is required to
      activate the collar of Tc-cnc expression in the mandibular segment but not the
      cap expression in the labrum. Tc-Dfd is also required for the activation of Tc
      prd in the endites of the mandible and maxillary appendages. CONCLUSIONS: Tc-cnc
      is necessary for patterning the mandibular segment of Tribolium. Together, Tc-cnc
      and Tc-Dfd cooperate to specify mandibular identity, as in Drosophila. Expression
      patterns of the homologs of cnc and Dfd are conserved in mandibulate arthropods
      suggesting that the mandible specifying function of cnc is likely to be conserved
      across the mandibulate arthropods.

PMID- 23114107
TI  - Guidelines for personal privacy protection in peer-reviewed journals.

PMID- 23114108
TI  - A cadaveric model for pericardiocentesis training.
AB  - BACKGROUND: Pericardiocentesis is a rare but potentially life-saving procedure.
      Improper technique can lead to life-threatening complications. DISCUSSION:
      Described is a cadaveric training model developed to train providers. CONCLUSION:
      This cadaveric model allows trainees to familiarize themselves with both proper
      landmark and ultrasound-based pericardiocentesis technique.

PMID- 23114109
TI  - Fresh frozen plasma for progressive and refractory angiotensin-converting enzyme
      inhibitor-induced angioedema.
AB  - BACKGROUND: Angioedema secondary to angiotensin-converting enzyme inhibitors
      (ACEI) is a commonly encountered problem in the Emergency Department (ED). The
      treatment of ACEI-induced edema with conventional methods such as epinephrine,
      steroids, and antihistamines is usually not effective. There is limited
      experience using bradykinin receptor blockers and fresh frozen plasma (FFP) as a
      treatment modality for ACEI-induced angioedema. OBJECTIVE: To emphasize
      alternative treatment option for ACEI-induced angioedema in the ED. CASE REPORTS:
      We report a case series of progressive and refractory presumed ACEI-induced
      angioedema that all improved in temporal association with administration of FFP,
      with a brief review of the literature. CONCLUSION: There was a temporal
      association between the administration of FFP and improvement in angioedema in
      seven cases of presumed ACEI-induced angioedema that were refractory to
      antihistamines, corticosteroids, and epinephrine.

PMID- 23114110
TI  - CMV and Immunosenescence: from basics to clinics.
AB  - Alone among herpesviruses, persistent Cytomegalovirus (CMV) markedly alters the
      numbers and proportions of peripheral immune cells in infected-vs-uninfected
      people. Because the rate of CMV infection increases with age in most countries,
      it has been suggested that it drives or at least exacerbates "immunosenescence".
      This contention remains controversial and was the primary subject of the Third
      International Workshop on CMV & Immunosenescence which was held in Cordoba,
      Spain, 15-16th March, 2012. Discussions focused on several main themes including
      the effects of CMV on adaptive immunity and immunosenescence, characterization of
      CMV-specific T cells, impact of CMV infection and ageing on innate immunity, and
      finally, most important, the clinical implications of immunosenescence and CMV
      infection. Here we summarize the major findings of this workshop.

PMID- 23114111
TI  - Long term survival results for gastric GIST: is laparoscopic surgery for large
      gastric GIST feasible?
AB  - BACKGROUND: Recently, laparoscopic resection for relatively small sized gastric
      gastrointestinal stromal tumors (GISTs) has been widely accepted as minimally
      invasive surgery. However, no report on the long-term safety and efficacy of this
      surgery for large sized gastric GISTs has been published to date. METHODS:
      Between July 1998 and January 2011, 104 consecutive patients who underwent
      resection for gastric GISTs were enrolled in this retrospective study. We
      assessed the clinicopathological characteristics, postoperative outcomes, patient
      survival, and tumor recurrence. RESULTS: Of the 104 patients with gastric GISTs
      who were included in the study, there were 47 males and 57 females whose mean age
      was 59.8 years. Sixty-four patients (61.5%) had symptoms associated with tumor.
      Ten patients included in the group 1, 49 in the group 2, 15 in the group 3a, 9 in
      the group 5, 14 in the group 6a, and 7 in the group 6b. There was one minor
      complication and no mortalities. Recurrence was noted in 5 patients, with a
      median follow-up period of 49.3 months (range, 8.4 to 164.4). The 5-year overall
      and disease free survival rates of 104 patients were 98.6% and 94.8%,
      respectively. When comparing large tumor (5-10 cm) between laparoscopic and open
      surgery, there were statistically differences in age, tumor size, tumor location,
      and length of hospitalization. There were no statistical differences in the 5
      year survival rate between laparoscopic and open surgery for large tumor (5
      10cm). CONCLUSION: Laparoscopic surgery is feasible and effective as an oncologic
      treatment of gastric GISTs. Moreover, laparoscopic surgery can be an acceptable
      alternative to open methods for gastric GISTs of size bigger than 5 cm.

PMID- 23114112
TI  - Conformational and dynamical properties of ultra-soft colloids in semi-dilute
      solutions under shear flow.
AB  - We investigate structural and dynamical properties of ultra-soft colloids in
      dilute and semi-dilute solutions by hybrid mesoscale simulations under linear
      shear flow. In particular, the influence of functionality on these properties is
      addressed. Our study combines molecular dynamics simulations for the solute with
      the multiparticle collision dynamics approach for the coarse-grained solvent. The
      star polymers exhibit large conformational and orientational changes in shear
      flow, which we characterize by the radius of gyration tensor and the alignment
      angle. These quantities show a universal dependence on a concentration- and
      functionality-dependent Weissenberg number with slight deviations at high shear
      rates. Moreover, the star polymers display a rotational dynamics with a shear
      rate- and concentration-dependent rotation frequency. We attribute the
      concentration dependence to the screening of hydrodynamic interactions in semi
      dilute star-polymer solutions.

PMID- 23114113
TI  - Owner-collected swabs of pets: a method fit for the purpose of zoonoses research.
AB  - As part of the preparation of a large cohort study in the entire German
      population, this study examined the feasibility of cat and dog owners collecting
      nasal and oral swabs of their animals at home as a method of assessing exposure
      to zoonoses. In veterinary clinics in Hannover, Germany, 100 pet owners were
      recruited. Nasal and oral swabs of pets were taken by a veterinarian at the
      clinic and owners took swabs at home. Swabs were analysed regarding bacterial
      growth and compared (owner vs. vet) using Cohen's kappa and McNemar's test. The
      return rate of kits was 92%, and 77% of owners thought it unnecessary to have
      veterinarian assistance to swab the mouth. McNemar's test results: oral swabs 78%
      agreement with Gram-positive bacterial growth, 87% agreement with Gram-negative
      bacterial growth; with similar results for nasal swabs. Although sample quality
      differed, this method allowed the receipt of swabs from pets in order to obtain
      information about colonization with zoonotic pathogens.

PMID- 23114114
TI  - Microscopic theory for anisotropic pair correlations in driven binary mixtures.
AB  - A  self-consistent microscopic approach to calculate non-equilibrium pair
      correlations in strongly interacting driven binary mixtures is presented. The
      theory is derived from the many-body Smoluchowski equation for interacting
      Brownian particles by employing Kirkwood's superposition approximation as a
      closure relation. It is shown that the pair correlations can exhibit notable
      anisotropy and a strong tendency to laning in the driving direction. Furthermore,
      there are strong indications that pair correlations are characterized by a long
      range decay along the drive. The theoretical results are in good quantitative
      agreement with the complementary Brownian dynamics computer simulations.

PMID- 23114115
TI  - Anaemia in HIV-infected children: severity, types and effect on response to
      HAART.
AB  - BACKGROUND: HIV and anaemia are major health challenges in Africa. Anaemia in HIV
      infected individuals is associated with more rapid disease progression and a
      poorer prognosis if not addressed appropriately. This study aimed at determining
      the severity and types of anaemia among HIV infected children and its effect on
      short term response to antiretroviral therapy (ART). METHODS: At baseline,
      clinical and haematological parameters of 257 HIV-infected ART-naive children
      aged 3 months to 18 years were assessed to determine the prevalence, severity and
      types of anaemia. ART eligible patients were started on therapy according to WHO
      criteria, enrolled (n=88) into an observational cohort and followed up for 6
      months. RESULTS: Anaemia was present in 148/257 (57.6%) of children, including
      (93/148) 62.2% with mild anaemia, 47/148 (32.0%) moderate anaemia, and 7/148
      (4.8%) with severe anaemia. The mean haemoglobin (hb) was lower among children
      with more advanced HIV disease (p<0.0001). Microcytic-hypochromic anaemia (44.9%)
      was the commonest type of anaemia. Anaemia was independently associated with
      young age (p <0.0001), advanced HIV WHO disease stage (p = 0.034) and low CD4
      percentage (p = 0.048). The proportion of children who had attained viral
      suppression (viral load <400 copies/ml) at 3 months was significantly lower among
      the anaemic children, 31/58 (53.4%) compared to the non-anaemic children 26/30
      (86.7%) (p=0.002). However, the difference in clinical and immunological response
      between the anaemic and non-anaemic patients did not reach statistical
      significance. CONCLUSION: Anaemia is highly prevalent among HIV-infected children
      in a rural Ugandan clinic and is associated with poorer virological suppression.
      However, the anaemia did not impact clinical and immunological response to ART
      among these children.

PMID- 23114116
TI  - [Expression of SET-NUP214 fusion gene in patients with T-cell acute lymphoblastic
      leukemia and its clinical significance].
AB  - This study was aimed to investigate the occurrence and clinical significance of
      the SET-NUP214 fusion gene in patients with T-cell acute lymphoblastic leukemia
      (T-ALL), analyse clinical and biological characteristics in this disease. RT-PCR
      was used to detect the expression of SET-NUP214 fusion gene in 58 T-ALL cases.
      Interphase FISH and Array-CGH were used to detect the deletion of 9q34. Direct
      sequencing was applied to detect mutations of PHF6 and NOTCH1. The results showed
      that 6 out of 58 T-ALL cases (10.3%) were detected to have the SET-NUP214 fusion
      gene by RT-PCR. Besides T-lineage antigens, expression of CD13 and(or) CD33 were
      detected in all the 6 cases. Deletions of 9q34 were detected in 4 out of the 6
      patients by FISH. Array-CGH results of 3 SET-NUP214 positive T-ALL patients
      confirmed that this fusion gene was resulted from a cryptic deletion of
      9q34.11q34.13. PHF6 and NOTCH1 gene mutations were found in 4 and 5 out of 6 SET
      NUP214 positive T-ALL patients, respectively. It is concluded that SET-NUP214
      fusion gene is often resulted from del(9)(q34). PHF6 and NOTCH1 mutations may be
      potential leukemogenic event in SET-NUP214 fusion gene.

PMID- 23114117
TI  - [Expression of c-MPL in leukemic stem cells from acute myeloid leukemia
      patients].
AB  - This study was aimed to investigate the expression of c-MPL in acute myeloid
      leukemia (AML) and the correlation of the c-MPL expression with CD34 and CD38, so
      as to define the expression of c-MPL in leukemic stem cells. The expression
      levels of CD34, CD38 and c-MPL were detected by flow cytometry in bone marrow
      cells from 29 newly diagnosed AML patients. The relationship of c-MPL positive
      cell ratio with clinical parameters and correlation of c-MPL with CD34 and CD38
      expression in AML patients were analyzed. The results showed that expression
      level of c-MPL in AML patients was significantly higher than that of normal
      controls (P < 0.05), and the expression level of c-MPL did not correlate with
      age, sex, white blood cell count, AML1-ETO fusion gene and remission after
      chemotherapy, but the expression of c-MPL in M2 and M5 patients was higher than
      that of normal control (P < 0.05). Expression of c-MPL in CD34 positive AML
      patients was obviously higher than that in CD34 negative AML patients (P < 0.01).
      c-MPL was significantly higher expressed in CD34(+) cells than that in CD34(-)
      cells (P < 0.001), while c-MPL expression was not significantly different between
      CD34(+)CD38(-) and CD34(+)CD38(-) cell groups. Positive correlation between c-MPL
      and CD34 expression was observed (r = 0.380, P = 0.042). It is concluded that
      expression of c-MPL is higher in AML patients, and positively correlates with the
      expression level of CD34. The c-MPL expresses in leukemic stem cells.

PMID- 23114118
TI  - [Construction of miRNA sponge targeting miR-20a and stable expression in Jurkat
      leukemia cell line].
AB  - This study was aimed to construct miRNA sponge targeting miR-20a and to establish
      a stable cell line Jurkat-S, paving the way for further research on function of
      miR-20a and application of RNAi in gene therapy. One pair of two-repeated
      oligonucleotide sequences containing bulged sites that are mispaired opposite miR
      20a positions 9-12 was designed and synthesized with enzyme cutting sites. The
      annealed oligonucleotide fragments were subcloned into pCDNA3.0-L expressing
      vector. After double-enzyme cutting, the vector was ligated to the annealed
      oligonucleotide fragments again. Enzyme cutting and luciferase activity assay
      were performed for identification after four repeats. Then the ligated fragment
      was subcloned to lentivirus expressing vector. Virus particles were collected
      after the control or sponge vectors were co-transfected with the psPAX2 packaging
      plasmid and the envelope plasmid pMD2.G into HEK-293T cells using Lipofectamine
      2000. The Jurkat cells were transfused with recombinant lentivirus-transfusing
      units plus 6 ug/ml of Polybrene. Real-time PCR and Western blot were used to
      detect the mRNA and protein expression of P21 and E2F1 after lentivirus
      transfusion respectively. As a result, luciferase activity assay demonstrated
      that the sponge targeting miR-20a was constructed successfully and the virus was
      packaged in 293T. The titer of virus was 5*10(7) TU/ml. Stable transfected Jurkat
      S cell line was established. As was expected, the mRNA and protein level of P21
      and E2F1 was upregulated significantly in Jurkat-S cells. It is concluded that
      the miR-20a sponge is constructed successfully, and Jurkat-S stable cell line is
      established, in which the expression of miR-20a is inhibited stably.

PMID- 23114119
TI  - [Expression of DNMT gene in bone marrow of patients with acute myelogenous
      leukemia and its significance].
AB  - This study was aimed to explore the expression and significance of DNMT1 gene in
      bone marrow of patients with acute myelogenous leukemia (AML). The expression of
      DNMT1 gene was detected by real-time PCR in 30 healthy people and 126 AML
      patients. The results showed that the expression level of DNMT1 gene was lower in
      the 30 healthy people and was higher in AML patients. There was a marked decline
      in the expression level of DNMT1 gene after complete remission (CR) as compared
      with the initial treatment. The expression level of DNMT1 gene did not correlated
      with age, sex and the clinical characteristics at initial diagnosis such as white
      blood cell count and chromosomal karyotype in AML patients. The CR rate in AML
      patients with low expression level of DNMT1 gene was lower than that in those
      with high expression level. It is concluded that bone marrow DNMT1 gene level may
      play an important role in AML pathogenesis and can serve as an index in
      evaluating AML prognosis.

PMID- 23114120
TI  - [Effects of baicalin on HL-60 cell xenografts in nude mice and its mechanism].
AB  - This study was aimed to investigate the effects of baicalin on HL-60 cell
      xenografts in nude mice in vivo and explore its mechanism. Xenograft tumor model
      of HL-60 cells in nude mice was established, which was divided randomly into 6
      groups: negative control group (injection of 5% NaHCO(3)), 25, 50 and 100 mg/kg
      baicalin groups, combination group (50 mg/kg baicalin + 2 mg/kg VP16) and
      positive control group (VP16 4 mg/kg). The nude mice with HL-60 cell xenografts
      were treated with drugs via intraperitoneal injection daily. After treatment for
      14 days average weigh and inhibitory rate of transplanted tumor stripped from 5
      nude mice in each group were calculated, and the ultrastructure change of
      xenografts cells were tested by transmission electron microscopy. Histopathologic
      examination was used to observed the change of main organs in nude mice. The
      expression of signaling molecular PI3K/Akt proteins extracted from xenografts was
      detected by Western blot. The effects of baicalin on overall survival time in
      nude mice with HL-60 cell xenografts were evaluated. The results showed that
      baicalin could inhibit the growth of transplanted tumors in dose-dependent
      manner. There were more necrotic and apoptotic cells in mice of baicalin-treated
      groups and combination group than that in mice of negative control group.
      Baicalin could inhibit the proliferation of HL-60 cells in vivo by down
      regulating the PI3K/Akt/mTOR signal pathway, where the expressions of p-Akt, mTOR
      and p-mTOR proteins decreased compared with negative control group, and no
      significant difference of Akt expression was found between different groups.
      Compared with negative control group, the median survival time of mice in
      combination group was more prolongated (P < 0.05). It is concluded that baicalin
      can inhibit growth and induce apoptosis of HL-60 cell xenografts in nude mice,
      and prolong median survival time of nude mice. The possible mechanisms may be
      related to inhibition of Akt activity and down-regulation of the PI3K/Akt/mTOR
      signal pathway. The combination of baicalin and VP16 shows a synergistic effect
      on inhibiting growth of HL-60 cell xenografts in nude mice.

PMID- 23114121
TI  - [Effect of mPGES-1 inhibitor MK886 on cell cycle of leukemia HL-60 cells].
AB  - To investigate the effect of a microsomal prostaglandin E synthase-1 (mPGES-1)
      inhibitor MK886 on cell cycle of the human acute myeloid leukemia HL-60 cells. HL
      60 cells were treated with different concentration of MK886 (10, 25, 50 umol/L)
      for 24 h. Flow cytometry, Western blot and ELISA were used to measure cell cycle,
      cyclin D1, mPGES-1, PGE(2), Akt, P-Akt and C-MYC. The results indicated that
      after treated with MK886, the percentage of HL-60 cells decreased in G(0)/G(1)
      phase and increased in S phase, and expressions of mPGES-1, cyclin D1, P-Akt and
      C-MYC and synthesis of PGE(2) decreased significantly. It is concluded that MK886
      can arrest HL-60 cells in G(0)/G(1) phase, the mechanism of which is possibly
      associated to inhibition of mPGES-1 expression, reduction of PGE(2) synthesis,
      suppression of Akt phosphorylation and C-MYC expression, down-regulation of
      cyclin D1 expression.

PMID- 23114122
TI  - [Establishment of a new method for screening of CBFB-MYH11 fusion gene in acute
      myeloid leukemia and its value in clinical use].
AB  - This study was purposed to establish new method for detecting CBFB-MYH11 fusion
      gene in acute myeloid leukemia (AML) and to evaluate its value in clinical use.
      All fusion types of reported CBFB-MYH11 fusion gene were defined by search of
      references and databank, then the primers and probes were designed on this basis,
      and 3 positive plasmids and negative cell line as control were established. GUSB
      gene was also amplified as an internal reference. The primer/probe sets were
      tested with 3 positive plasmids and HL-60 cDNA using quantitative real-time PCR
      (qPCR) assays, which were then combined as a multiplex qPCR for simultaneous
      detection of CBFB-MYH11 and GUSB. After optimization, the multiplex qPCR assay
      demonstrated both high sensitivity (10 copies for all the 3 plasmids) and high
      specificity. Finally, the multiplex qPCR assay was clinically evaluated with 58
      AML patients, and 4 CBFB-MYH11-positive cases (6.9%) were detected, involving A
      type (3 cases) and J type (1 case). By comparison, the multiplex qPCR assay
      showed results concordant with sequencing results, and detected one case that was
      missed by cytogenetic analysis. It is concluded that a novel qPCR method for
      screening of CBFB-MYH11 fusion gene in AML is established. This method is fast,
      comprehensive, sensitive, specific, reliable, and should consider to be a robust
      tool for identification and management of AML patients with CBFB-MYH11 fusion
      gene.

PMID- 23114123
TI  - [Anti-leukemic effect of scutellaria extract SBX and its mechanisms].
AB  - This study was aimed to explore the anti-leukemic effect of scutellaria extract
      SBX in human leukemia cell lines and its mechanism. The leukemia cell lines,
      including HL-60, NB4, U937, K562 and Jurkat, were cultured in vitro and
      proliferative inhibition of these cell lines was detected by CellTiter-Glo
      Luminescent Cell Viability Assay in order to screen the most sensitive cell line.
      The effect of SBX on cell cycle was analyzed by flow cytometry and the protein
      expressions determined by Protein Pathway Array respectively. The results
      indicated that SBX (10 - 200 umol/L, for 72 h) significantly inhibited the
      proliferation of different leukemia cell lines in a dose-dependent manner (r
      value was 0.86, 0.88, 0.95, 0.94, 0.96, respectively), the HL-60 was the most
      sensitive cell line. Flow cytometric analysis showed that SBX (50, 10 umol/L, for
      48 h) arrested HL-60 cells in the G(0)/G(1) phase. In addition, protein
      expression of p-PKC alpha/betaII, p-p38, Cdc25B, XIAP of HL-60 cells increased,
      and p-AKT, p-SAPK/JNK, Notch4, Cdk4, Cdc2, cyclin E, Akt, Bcl-2, Bax, cdc42, TNF
      alpha, p27, CaMKKa decreased after exposure to SBX (50 umol/L, for 48 h). It is
      concluded that SBX can inhibit the proliferation of different leukemia cell
      lines, and HL-60 is a sensitive cell line. SBX significantly influences EGFR,
      Ras/Raf/MAPK and Notch signaling pathway, through which effects the expression of
      cell cycle-related proteins resulting in arrest of HL-60 cells in G(0)/G(1).

PMID- 23114124
TI  - [Effects of COX-2 inhibitor celecoxib on expressions of VEGF, b-FGF and TGF-beta
      mRNA in acute leukemia cells].
AB  - This study was aimed to investigate the influence and significance of celecoxib
      (specific inhibitor of cyclooxygenase-2) on mRNA expressions of vascular
      endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF),
      transforming growth factor beta (TGF-beta) in acute leukemia cells. The
      expressions of VEGF, b-FGF, TGF-beta mRNA were measured by RT-PCR in acute
      leukemia cells treated with celecoxib (80 umol/L, for 48 h) or with PBS. The
      results showed that the obvious expressions of VEGF, b-FGF, TGF-beta mRNA were
      observed in acute leukemia cells. By using Pearson correlation analysis, there
      was positive correlation between VEGF mRNA and b-FGF mRNA expressions (r = 0.559,
      P = 0.001), and negative correlation between VEGF and TGF-beta mRNA expressions
      (r = -0.4, P = 0.029). Expression levels of VEGF, b-FGF, TGF-beta mRNA in
      experimental group were lower than that in control group (P < 0.01). It is
      concluded that COX-2 inhibitor celecoxib can inhabit vascular endothelial growth
      through down-regulating the mRNA expression of VEGF, b-FGF and TGF-beta in acute
      leukemia cells. COX-2 inhibitor may offer supplemental effect for treating acute
      leukemia.

PMID- 23114125
TI  - [Stable interference on P210(bcr/abl) gene expression by lentiviral vector
      delivered shRNA in vitro and in vivo].
AB  - P210(bcr/abl) fusion gene is indispensable for generation and progression of
      chronic myeloid leukemia (CML). Small molecule inhibitors, such as imatinib, are
      effective for P210(bcr/abl) gene mediated CML, but drug resistance may occur. The
      unique fusion junction of P210(bcr/abl) gene is an attractive target for
      therapeutic intervention using RNA interference (RNAi). This study was purposed
      to constructed the BaF3 cell line by viral vector which can stably express
      P210(bcr/abl) shRNA and P210(bcr/abl) mRNA at the same time, and investigate the
      effect of lentiviral-victor-delivered shRNA on P210(bcr/abl) gene expression. The
      infective rate of lentiviral vector on BaF3 cells with P210(bcr/abl) gene was
      assayed by fluorescent microscopy; the cell proliferation ability was determined
      by trypan blue exclusion; the P210(bcr/abl) mRNA and protein expressions were
      detected by RT-PCR and Western blot respectively. The results found that stable
      expression of the P210(bcr/abl) shRNA resulted in obvious inhibition of
      P210(bcr/abl) mRNA and protein expression and increased sensitivity of these
      P210(bcr/abl) gene transformed Ba/F3 cells to imatinib. The IC(50) to imatinib in
      these cells decreased < 50% as compared with Ba/F3-P210(bcr/abl) cells which did
      not express P210(bcr/abl) mRNA. The survival time of the lethal dose irradiated
      mice induced by intravenous injection of these Ba/F3 cells was longer than the
      other group induced by Ba/F3-P210(bcr/abl). It is concluded that stable
      expression of shRNA targeting the P210(bcr/abl) gene fusion junction may
      potentiate the effects of conventional therapy for CML.

PMID- 23114126
TI  - [Evaluation of fluorescence in situ hybridization value in detection of chronic
      lymphocytic leukemia].
AB  - The aim of this study was to investigate the clinical value of fluorescence in
      situ hybridization (FISH) in detecting the genomic aberration of chronic
      lymphocytic leukemia (CLL). FISH was used for 32 patients who were newly
      diagnosed as CLL. Five types of fluorescence probes with labeled DNA probes were
      included as sequence specific probes D13S25 for 13q14.3, P53 for 17p13.1, ATM for
      11q22.3, RB1 for 13q14 and chromosomes 12. Meanwhile, FISH was used to detect
      IGH/CCND1 fusion gene in 10 CLL patients with untypical immunophenotypes. The
      results showed that out of 32 patients, 26 cases (81.3%) were abnormal including
      14 cases of D13S25 deletion, 11 of RB1 deletion, 9 of trisomia 12, 6 cases of P53
      deletion, and 1 of ATM deletion. 12 cases showed 1 kind of genomic aberration,
      including 7 cases of trisomia 12, 3 cases of D13S25 deletion, 1 of P53 deletion,
      1 of ATM deletion. 11 eases displayed 2 kinds of abnormalities. Out of 11 cases,
      7 were D13S25/RB1 deletion, 4 were of P53 deletion, and 3 cases had 3 kinds of
      abnormalities. Among 10 patients with CD5(+)CD23(-), two were positive with
      IGH/CCND1. It is concluded that the FISH can improve the detecting of chromosomal
      abnormalities in CLL, and every abnormality has its special feature. Detection of
      IGH/CCND1 seems important in diagnoses of CLL.

PMID- 23114127
TI  - [Diagnostic value of fluorescence in situ hybridization for children with acute
      myeloid leukemia].
AB  - This study was purposed to investigate the diagnostic value of fluorescence in
      situ hybridization (FISH) technique for the childhood acute myeloid leukemia
      (AML). The medical data of 179 children with AML (aged <= 16 years) were
      retrospectively studied, who were initially diagnosed in our hospital from April
      2005 to April 2010. Through the analysis of the results of FISH, chromosome
      banding analysis and polymerase chain reaction, the difference and
      complementarity between FISH and other 2 methods for detecting the fusion genes
      were explored. The results indicated that the detection rate of genetic
      abnormality with FISH was higher. The PML/RARalpha probe was used in 27 AML-M3
      patients, 22 out of whom were evaluated as PML/RARalpha positive. The AML1/ETO
      probe was used in 24 AML-M2b patients and all of them were evaluated as AML1/ETO
      positive. The CBFbeta/MYH11 probe was used in 4 AML-M4Eo patients and all of them
      were evaluated as CBFbeta/MYH11 positive. It is concluded that FISH is a
      sensitive method for detecting fusion genes and the results of FISH have a good
      correlation with the chromosome banding analysis and polymerase chain reaction.
      The combination of FISH with other 2 methods improves the detection rate of
      genetic abnormality, which is useful for the diagnosis and typing of childhood
      AML.

PMID- 23114128
TI  - [Characteristics and monitoring of minimal residual disease in patients with T
      acute lymphoid leukemia by flow cytometry with two 4-color combinations of
      fluorescent antibodies].
AB  - The purpose of this study was to establish a method for the monitoring of minimal
      residual disease (MRD) in bone marrow samples of the children with T acute
      lymphoid leukemia (T-ALL), and to evaluate its value in clinical application. The
      immuno-phenotype of the leukemic cells were detected by flow cytometry with two
      sets of 4-color combinations of antibodies against TdT/CD5/cCD3/HLA
      DR(+)CD19(+)CD33 and CD34/CD5/cCD3/HLA-DR(+)CD19(+)CD33 in 32 cases of de novo T
      ALL and were compared with the results in 10 normal controls. The antibody
      combination in regions of the two-parameter plots where the leukemic cells
      appeared were different from the normal cells was screened as the effective
      combination which was used to monitor MRD in the bone marrows of the T-ALL
      children after the inductive treatment. The results indicated that the respective
      effective frequencies of antibodies against TdT/CD5/cCD3/HLA-DR(+)CD19(+)CD33 and
      CD34/CD5/cCD3/HLA-DR(+)CD19(+)CD33 were 90.6% and 62.5%. 32 cases of childhood T
      ALL were successively screened for antibodies combinations of interest and were
      identified in 100% (32/32) of these cases. After inductive treatment, the
      positive rate in 129 times of MRD monitoring was 19.4% (25/129) by flow cytometry
      and 5.43% (7/129) by FAB morphology. It is concluded that monitoring MRD in
      patients with T-ALL by flow cytometry with two 4 color combinations of
      fluorescent antibodies is an quick and effective method. The sensitivity of this
      method is high and it may be of important significance for the treatment and
      prognostic evaluation in childhood T-ALL.

PMID- 23114129
TI  - [Detection and clinical features of MLL gene rearrangement in adult patients with
      acute leukemia].
AB  - This study was purposed to investigate the incidence of mixed lineage leukemia
      (MLL) gene rearrangement and partner gene types as well as the clinical features
      and prognosis of acute leukemia (AL) with this rearrangement through detection in
      adult AL using combination of 3 techniques, and to evaluate the clinical value of
      this combination detection. The MLL gene rearrangement in 183 cases of adult AL
      was detected by combination of conventional cytogenetics, split signal FISH and
      multiplex nested PCR. The results showed that the incidence of MLL rearrangements
      in adult patients with AL was low (8.2%), and MLL-AF4 fusion gene was most common
      and predominant in acute lymphoblastic leukemia (ALL), while the MLL-AF6 and MLL
      AF9 were most frequent in acute myeloid leukemia (AML). Extramedullary
      involvements were found in 40% of MLL-rearranged AL patients, and 33.3% of
      patients with MLL-rearranged AL reached to complete remission within 30 days
      during induction chemotherapy. In addition, in this cohort of MLL-rearranged
      adult AL patients, the 3-month relapse rate and 6-month overall survival rate
      were 50.0% and 50.0% respectively. It is concluded that the rate of missed
      diagnosis of CC technique for patients with MLL-rearranged AL reached to 60% in
      this study, while the combination of CC, FISH and multiplex nested PCR has been
      confirmed to have important significance for evaluating prognosis and conducting
      clinical therapy of patients with MLL-rearranged AL.

PMID- 23114130
TI  - [Curative efficiency of rituximab combined with autologous cytokine induced
      killer cells on aged patient with orbital diffuse large B cell lymphoma].
AB  - The aim of this study was to observe the curative effects and safety of
      autologous cytokine induced killer (CIK) cells in treatment of aged patients with
      orbital diffuse large B cell lymphoma after rituximab therapy. The patient was
      given rituximab three times with low dose COP chemotherapy one time when he was
      diagnosed with orbital diffuse large B cell lymphoma. Two months later, the
      patient began to receive five cycles CIK cells infusion. One course of therapy
      was defined as follows: about (2-3)*10(9) of CIK cells (survival rate > 95%) was
      transfused twice and then rhIL-2 (1 MU daily) was subcutaneously administered for
      10 consecutive days. Efficacy and adverse effect was observed during or after CIK
      cells infusion. The results showed that the peripheral blood mononuclear cells of
      the patient could be cultured and expanded into CIK cells. The majority of CIK
      cells was positive for CD3 and CD8 after culture. The CD3(+)CD56(+) cells
      markedly increased after culture. After two cycles of CIK cell infusion, the
      orbital lymphoma and possible involvement of the kidney disappeared. The patient
      obtained complete remission after five cycles of CIK cells infusion. The side
      effects of CIK cell treatment were minor. It is concluded that CIK cell infusion
      may prevent recurrence, prolong progression-free survival and improve quality of
      life after rituximab (alone or with chemotherapy) for aged patients with orbital
      diffuse large B-cell lymphoma.

PMID- 23114131
TI  - [Inhibitory effect of histone deacetylase inhibitor LBH589 on multiple myeloma
      MM1R cells in vitro].
AB  - This study was purposed to explore the effect of a new generation of histone
      deacetylase inhibitor LBH589 alone or combined with bortezomib (Bor) on multiple
      myeloma cells (MM1R) in vitro. The effect of LBH589 (10, 20, 50 nmol/L) alone or
      combined with Bor (10, 20 nmol/L) on MM1R proliferation was detected by MTT
      method; the effect of LBH589 on cell cycle and apoptosis of MM1R cells were
      determined by flow cytometry; the histone H4 acetylation level of MM1R cells
      treated with LBH589 (10, 20, 50 nmol/L) for 24 h was analyzed by Western blot.
      The results showed that the LBH589 alone or combined with Bor all could inhibit
      the proliferation of MM1R cells in a concentration- and time-dependent manner.
      After MM1R cells were treated with drugs for 48 h, the cells in G(0)/G(1) phase
      increased, the cells in G(2)/M and S phase decreased, suggesting the arrest of
      cells in G(0)/G(1) phase, at the same time, the apoptosis rate of MM1R cells
      treated with drugs increased in a concentration-dependent manner, while the
      effect of LBH589 combined with Bor was more obvious than that of LBH589 alone (P
      < 0.001). Western blot analysis showed that the histone H4 acetylation level was
      enhanced in concentration-dependent manner after MM1R cells were treated with
      different concentrations of LBH589 for 24 h. It is concluded that the LBH589 can
      inhibit the proliferation of MM1R cells, block the cell cycle, induce cell
      apoptosis, moreover LBH589 combined with Bor has synergistic effect on MM1R
      cells.

PMID- 23114132
TI  - [Silencing of ICSBP/IRF8 expression in U226 cells and bone marrow mononuclear
      cells from patients with multiple myeloma].
AB  - The objective of this study was to investigate expression of interferon
      regulatory factors (ICSBP/IRF8) and the potential role of DNA methylation in
      silencing ICSBP/IRF8 gene in multiple myeloma (MM) cell line U266 and bone marrow
      mononuclear cells from 10 MM patients (MM-BMMNC). The bone marrow mononuclear
      cells from 10 healthy persons (N-BMMNC) were collected and used as normal
      controls. Expression of ICSBP/IRF8 gene was detected by real-time fluorescence
      quantitative PCR (using 2(-DeltaDeltaCT) to calculate); DNA methylation level of
      the ICSBP/IRF8 gene was measured using methylation-specific PCR (using the ratio
      of interest gene ICSBP/IRF8 and internal reference beta-actin expression as
      results). The results showed that as compared with N-BMMNC the lower expression
      of ICSBP/IRF8 gene was found in U266 cells and MM-BMMNC, the hypermethylation of
      the CpG island in the ICSBP/IRF8 promoter was observed, there were significant
      differences between N-BMMNC and MM-BMMNC or U266 cells (P < 0.05). It is
      concluded that the expression of ICSBP/IRF8 gene can be silenced in the MM-BMMNC
      and U226 cells. As the hypermethylation of CpG island in ICSBP/IRF8 promoter is a
      frequent event in MM cells, the ICSBP/IRF8 gene silencing caused by DNA
      methylation may take part in the pathogenesis and development of MM.

PMID- 23114133
TI  - [BAFF level in bone marrow and expression of BAFF receptor on B cells in multiple
      myeloma patients].
AB  - This study was purposed to investigate the B cell-activating factor belonging to
      the TNF family (BAFF) and a proliferation-inducing ligand (APRIL) levels in bone
      marrow, and the BAFF receptor expression level on B cells in multiple myeloma
      (MM) patients, in order to explore the characteristics of B cells in bone marrow
      of MM patients. MM patients were studied before treatment (newly diagnosed group,
      19 patients) and after treatment with improvement (stable group, 17 patients), 10
      non-hematologic patients were selected as control (control group). The BAFF
      receptors (BAFF-R) and transmembrane activator and calcium modulator and
      cyclophilin ligand interactor (TACI) on B cell (CD19(+)), naive B cell
      (CD19(+)IgD(+)) and memory B cell (CD19(+)CD27(+)) of bone marrow in all groups
      were detected by flow cytometry. The BAFF, APRIL level in bone marrow supernatant
      were tested with ELISA. The results showed that the BAFF-R expression level on
      CD19(+) cells in newly diagnosed group were higher than that in stable group and
      control group; there was no significant difference between the BAFF-R expression
      level on CD19(+)IgD(+) cells in newly diagnosed group and stable group, but BAFF
      R expression level on CD19(+)IgD(+) cells in newly diagnosed group was higher
      than that in control group; the BAFF-R expression level on CD19(+)CD27(+) cells
      in newly group was higher than that in stable group and control group; there was
      no significant difference between the BAFF-R expression level on CD19(+) cells,
      CD19(+)IgD(+) cells or CD19(+)CD27(+) cells in stable group and control group.
      There was no significant difference among the TACI expression level on CD19(+)
      cells, CD19(+)IgD(+) cells or CD19(+)CD27(+) cells in newly diagnosed group,
      stable group and control group. The bone marrow supernatant BAFF level in newly
      diagnosed group was higher than that in stable group and control group, but there
      was no significant difference between stable group and control group. There was
      no significant difference among the bone marrow TACI levels in newly diagnosed
      group, stable group and control group. It is concluded that both the bone marrow
      BAFF level and the BAFF-R expression level on CD19(+) cell, CD19(+)IgD(+) cells
      and CD19(+)CD27(+) cells in MM patients increase, which may help to stimulate B
      cells, thereby may relate with to MM pathogenesis.

PMID- 23114134
TI  - [Influence of bisphosphonate combined with chemotherapy on bone mineral density
      of patients with multiple myeloma].
AB  - The purpose of this study was to investigate the effect of bisphosphonate
      combined with chemotherapy on bone mineral density (BMD) of patients with
      multiple myeloma (MM) and analyse its value of BMD detection in clinic of these
      patients. 53 MM cases were enrolled in this study, including 33 newly diagnosed,
      10 refractory/relapsed and 10 stable cases. They were divided randomly into two
      groups, 33 MM cases were treated with bisphosphonates combined with chemotherapy
      and 20 MM cases were treated with chemotherapy alone. The chemotherapy schedules
      for all patients were same. BMD was tested using the dual energy X-ray
      absorptiometry at 2 time points, i.e. pretreatment (basal level) and 12 months
      after treatment with chemotherapy and bisphosphonates. Comparisons was performed
      with t tests using SPSS 11.0 software. The results indicated that there was minor
      difference between 2 groups for BMD scores of whole body and lumbar vertebra (L1
      L4), but no difference for scores of the near-end of left femur. After treatment
      for 12 months, all BMD scores (whole body, lumbar vertebra and the near-end of
      left femur) increased significantly in the bisphosphonate combined with
      chemotherapy group (P < 0.05). In contrast, only minor changes were seen in
      chemotherapy alone group. It is concluded that the bisphosphonate combined with
      chemotherapy has displayed promotive effect on BMD of MM patients, the detection
      of BMD is sensitive and special method for monitoring therapeutic effect of
      bisphosphonate in MM patients, thus has useful value in clinic of these patients.

PMID- 23114135
TI  - [A case report of myelodysplastic/myeloproliferative disease unclassifiable with
      karyotype aberration of trisomy 8 and JAK2 mutation].
AB  - This study aimed to investigate the relationship between clinical features of
      myelodysplastic/myeloproliferative disease, unclassifiable (MDS/MPD-U), karyotype
      of chromosome and JAK2 mutation in 1 case. The clinical features, karyotype and
      JAK2 mutation of the patient with MDS/MPD-U were studied by means of bone marrow
      biopsy, karyotype analysis and ARMS-PCR technique. The results indicated that the
      typical micromegakaryocytes and thrombocytosis, karyotype aberration of trisomy 8
      as well as JAK2 V617F mutation were found in this patient. It is concluded that
      the patient was diagnosed as MDS/MPD-U with trisomy 8 and JAK2 V617F mutation.
      The data of this patient will provide evidence for studying correlation of
      chromosome karyotype aberration with JAK2 V617F mutation and for evaluating
      prognosis of MDS/MPD-U.

PMID- 23114136
TI  - [Methylation of FHIT gene promoter region in DNA from plasma of patients with
      myelodysplastic syndromes and demethylating effect of decitabine].
AB  - This study was aimed to detect the methylation status of FHIT gene promoter
      region in the DNA from plasma of patients with myelodysplastic syndrome (MDS),
      and to investigate the demethylating effect of decitabine. Methylation-specific
      PCR method was used to detect the methylation status of FHIT gene promoter region
      in the DNA from plasma of 4 patients with MDS before and after treatment with
      decitabine plus semis CAG therapy (among them, 1 case of newly diagnosed MDS, 3
      cases progressed into acute leukemia). The results indicated that 3 cases were
      found to have an increased methylation in the promoter region. After treatment
      with decitabine plus semis CAG, increased methylation was reversed in 2 cases. In
      4 cases, 2 cases displayed clinical response. It is concluded that FHIT gene
      hypermethylation is associated with MDS pathogenesis. Decitabine has
      demethylating effect on the FHIT gene hypermethylation of plasma from MDS
      patients. Detecting the methylation status of FHIT gene in DNA from plasma may
      play a role in MDS auxiliary diagnosis or prognosis.

PMID- 23114137
TI  - [Analysis of miRNA differential expression in peripheral blood cells of primary
      immune thrombocytopenia patients].
AB  - This study was purposed to clarify the difference of microRNA (miRNA) expression
      in the peripheral blood cells of patients with primary immune thrombocytopenia
      (ITP) and normal controls. Exqion miRCURY(TM) microarray was used to investigate
      differentially expressed miRNA of peripheral blood cells obtained from affected
      ITP patients and the healthy controls. Cluster analysis was used to identify
      miRNA expression profile between the ITP patients and the healthy controls. Real
      time PCR was used for validation. The results showed that a total of 159 miRNA
      were found to be differentially expressed in ITP patients compared to the
      controls, with 79 up-regulated and 80 down-regulated. Based on these
      differentially expressed miRNA, a tree with clear distinction between the
      controls and ITP patients was generated by cluster analysis. Real-time PCR
      confirmed microarray analysis results. It is concluded that differentially
      expressed miRNA were found in the peripheral blood cells from ITP patients, which
      may be potential novel biomarkers for ITP as well as help to elucidate pathogenic
      mechanisms of ITP.

PMID- 23114138
TI  - [Expressions of Th17 cells and interleukin 17 in patients with primary immune
      thrombocytopenia and their clinical significance].
AB  - The aim of this study was to detect the rate of T-helper (Th)17 cells and
      interleukin (IL)-17 level in peripheral blood of patients with primary immune
      thrombocytopenia (ITP) and to explore their clinical significance. The proportion
      of Th17 cells from 48 patients with ITP and 28 healthy controls was detected by
      flow cytometry, and the IL-17 level was evaluated by enzyme-linked immunosorbent
      assay (ELISA). The results showed that the percentage of Th17 cells in ITP group
      was (1.40 +/- 1.35)%, which was significantly higher than that in healthy control
      group (P < 0.05), but in the glucocorticoid hormone-treated group it was
      significantly lower than that in treated group without glucocorticoid hormone(P <
      0.05). The level of IL-17 expressed by Th17 cells in ITP patients was (19.624 +/-
      5.187) pg/ml, which was higher than that in the healthy control group (P < 0.05),
      it was lower in the glucocorticoid hormone treated group than that in treated
      group without glucocorticoid hormone, but there was no statistically significant
      difference between the glucocorticoid treated and treated group without
      glucocorticoid hormone (P > 0.05). It is concluded that the Th17 cells may
      involve in the pathogenesis of ITP, and the glucocorticoid hormone probably plays
      a therapeutic role through inhibiting Th17 cells.

PMID- 23114139
TI  - [Expression of TRF1, TRF2 and RAP1 mRNA in peripheral blood mononuclear cells of
      patients with acquired aplastic anemia].
AB  - This study was aimed to investigate the expression levels of TRF1, TRF2 and RAP1
      mRNA in peripheral blood mononuclear cells of patients with acquired aplastic
      anemia, and to explore their relation with onset of acquired aplastic anemia.
      Peripheral blood mononuclear cells of 40 patients with acquired aplastic anemia
      and 20 normal subjects as control were collected to detect mRNA expression of
      TRF1, TRF2 and RAP1 by using real-time quantitative polymerase chain reaction.
      The results showed that the expression levels of TRF1 and RAP1 in peripheral
      blood mononuclear cells of patients with acquired aplastic anemia were
      significantly higher than that in normal controls (P < 0.05), while the
      expression level of TRF2 was lower than that in normal controls (P < 0.01). There
      was significant correlation between TRF2 and RAP1 expressions level (r = 0.522, P
      = 0.001). It is concluded that the changes in expression levels of TRF1, TRF2 and
      RAP1 may play a role in the pathogenesis of acquired aplastic anemia.

PMID- 23114140
TI  - [Efficacy of adoptive immunotherapy after mixed hematopoietic stem cell
      transplantation on acute myeloid leukemia].
AB  - The purpose of this study was to investigate the efficacy of treatment with
      haploidentical donor's lymphocyte infusion(hiDLI) combined with interleukin-2 (IL
      2) after transplantation of autologous peripheral blood stem cells mixed with
      haploidentical allogeneic bone marrow (mix-HSCT) for acute myeloid leukemia
      (AML). 49 patients diagnosed as AML were enrolled in this study. After
      preconditioning with TBI plus VEMAC regimen, all patients received mix-HSCT.
      Autologous peripheral blood hematopoietic stem cells were mobilized with
      chemotherapy-combined G-CSF, and haploidentical allogeneic bone marrow cells were
      not mobilized with G-CSF. 33 patients in test group were treated with hiDLI plus
      IL-2 for 1-8 times after hematopoietic reconstruction, 16 patients in control
      group received mix-HSCT only. All the patients were followed-up for more than 3
      years. The results showed that all the patients obtained hematopoietic
      reconstruction, and no graft-versus-host disease (GVHD) was found. In two groups,
      the median time of absolute neutrophil count (ANC) >= 0.5*10(9)/L was 14 (12 -
      18) and 14 (11 - 16) days, and WBC count >= 4.0*10(9)/L was 17 (16 - 22) and
      18(17 - 20) days, Plt count >= 50*10(8)/L were 25 (24 - 29) and 25 (23 - 26)
      days. 9 patients in test group formed mixed chimerism (46XX/46XY) and sustained
      about 3 - 12 months; disease-free survival (DFS) was 63.6%, 3 patients in control
      group formed mixed chimerism (46XX/46XY), persistent about 3-6 months; DFS was
      50.0%. It is concluded that treatment with hiDLI plus IL-2 after mix-HSCT for AML
      patients may increase DFS efficiently.

PMID- 23114141
TI  - [Detection of NK and NKT cells in peripheral blood of patients with cGVHD and its
      significance].
AB  - The aim of this study was to investigate the correlation of NK and NKT cells in
      peripheral blood of patients undergoing allogeneic hematopoietic stem cell
      transplantation (allo-HSCT) with chronic graft-versus-host disease (cGVHD). 64
      patients undergoing allo-HSCT in Guangdong Provincial People Hospital were
      studied retrospectively. Among 64 cases, 21 cases were did not develop with
      cGVHD, 43 cases (mild 15, moderate 18, severe 10) were recorded with cGVHD. The
      frequency of NK and NKT cells in peripheral blood of patients were measured by
      flow cytometry. The counts of NK and NKT cells were measured by automatic five
      sort hematology cyto-analyser (LH-750). The frequency and counts of NK and NKT
      cells between patients with non-cGVHD and patients with different status of cGVHD
      were analysed. The results indicated that as compared with the non-cGVHD
      patients, the frequency and counts of NK cells in patients with cGVHD obviously
      reduced (P < 0.05), the frequency and count of NKT cells were did not changed
      significantly. The frequency and counts of NK cells gradually decreased within
      the different status of cGVHD, the frequency and counts of NK cells in severe
      cGVHD were significantly lower than that in mild-cGVHD. It is concluded that NK
      cells may play an important role in the incidence and development of cGVHD. The
      detection of frequency and counts of NK cells should be helpful to early diagnose
      cGVHD and provide valuable clues for assessing the severity of illnesses. NKT
      cells may have little effect on the incidence and development of cGVHD.

PMID- 23114142
TI  - [Effect of alloreactive natural killer cells on immune reconstitution in mouse
      haploidentical bone marrow transplantation].
AB  - The study was purposed to investigate the effect of alloreactive natural killer
      (alloNK) cells on immune reconstitution in murine haploidentical bone marrow
      transplantation (BMT). The murine model of haploidentical BMT was established by
      using (C57BL/6*BALB/c)BCF(1)(H-2(d/b)) mouse as the donor, and BALB/c (H-2(d))
      mouse as the recipient. Recipient mice were divided into BMT group, non-allo
      reactive NK (non-alloNK) cell group and alloNK cell group according to different
      transfusion. The effect of adding alloNK cells to transfusion was assessed by
      thymus pathology, the proportion of spleen NK cells, the spleen cell
      proliferation, the IFN-gamma and IL-4 concentrations product at 24 and 48 h of
      recipient spleen cell culture supernatant at 2 months after BMT. The results
      showed that there were no obvious difference in thymus tissue among 3 groups
      under the optical microscope. The proportion of recipient spleen NK cells in non
      alloNK group was significantly lower than that in BMT group (P < 0.05). There was
      no significant difference in proliferation of the recipient spleen cells among 3
      groups at 2 months after BMT. The IFN-gamma concentration product at 24 and 48 h
      of recipient spleen cell culture supernatant in alloNK group was significantly
      lower than that in other 2 groups at 2 months after BMT (P < 0.05). The IL-4
      concentration in each group was not significantly different (P > 0.05). It is
      concluded that alloNK cells do not damage the thymus structure and may induce Th2
      immune response in murine haploidentical BMT.

PMID- 23114143
TI  - [Effect of different oxygen concentrations on biological properties of bone
      marrow hematopoietic stem cells of mice].
AB  - This study purposed to investigate the effects of different oxygen concentrations
      and reactive oxygen species (ROS) on the biological characteristics of
      hematopoietic stem cells (HSC) and their possible mechanisms through simulating
      oxygen environment to which the peripheral blood HSC are subjected in peripheral
      blood HSCT. The proliferation ability, cell cycle, directed differentiation
      ability, ROS level and hematopoietic reconstitution ability of Lin(-)c-kit(+)Sca
      1(+) BMHSC were detected by using in vitro amplification test, directional
      differentiation test, cell cycle analysis, ROS assay and transplantation of Lin(
      )c-kit(+)Sca-1(+) HSC from sublethally irradiated mice respectively. The results
      showed that oxygen concentrations lower than normal oxygen concentration,
      especially in hypoxic oxygen environment, could reduce ROS generation and amplify
      more primitive CD34(+)AC133(+) HSC and active CD34(+) HSC, and maintain more stem
      cells in the G(0)/G(1) phase, which is more helpful to the growth of CFU-S and
      viability of mice. At the same time, BMHSC exposed to normal oxygen level or
      inconstant and greatly changed oxygen concentrations could produce a high level
      of ROS, and the above-mentioned features and functional indicators are relatively
      low. It is concluded that ROS levels of HSC in BMHSCT are closely related with
      the oxygen concentration surrounding the cells and its stability. Low oxygen
      concentration and antioxidant intervention are helpful to transplantation of
      BMHSC.

PMID- 23114144
TI  - [Effect of human placental extract on proliferation of human umbilical cord blood
      CD34(+) cells in vitro].
AB  - The study was aimed to investigate the hematopoietic function of placenta tissue
      and clarify the effect of human placental chorionic tissue in different periods
      on proliferation of hematopoietic stem cells in vitro, in order to further
      understand the changes of the hematopoietic function of placenta with the time
      prolonging. The experiments were divided into four groups: early placenta (group
      B), mid-term placenta (group C), full-term placenta (group D), and blank group
      (group A). The hematopoietic stem cells were amplified in co-culture way, and the
      colony formation ability after the expansion was observed. The results showed
      that compared to initial concentration, the CD34(+) cells cultured with full-term
      placenta were amplified by (2.60 +/- 0.20) times, which was significantly higher
      than those CD34(+) cells cultured with mid-term placenta (1.74 +/- 0.24) and
      early placenta (1.14 +/- 0.12), but that in blank group was reduced without
      amplification. After culture for 14 days, the colony number of group C and group
      D were significantly higher than that of group A and group B. Among them the
      number of CFU-GM, CFU-GEMM, BFU-E of group C all were a little higher than that
      of group D. It is concluded that human placental extract in different period
      without any exogenous cell factors all can support the proliferation of
      hematopoietic stem cells, this ability is getting stronger with time increasing.
      The colony formation ability of the amplified cells shows weakened after the
      first increase, this colony formation ability of the amplified cells in group C
      is strongest, slightly stronger than that of group D.

PMID- 23114145
TI  - [Effect of osteogenically and adipogenically differentiated bone mesenchymal stem
      cells from mouse on osteoclast formation].
AB  - This study was purposed to investigate the regulatory effects of differentiating
      mesenchymal stem cells (MSC) on osteoclast formation. The MSC from mouse compact
      bones were cultured and induced into osteoblasts and adipocytes for one week. To
      test their regulatory effect on osteoclastogenesis, osteogenically differentiated
      and adipogenically differentiated MSC were co-cultured with CD11b(+) monocytes
      and osteoclasts were identified with in situ tartrate-resistant acid phosphatase
      (TRAP) staining. The results showed that differentiated MSC supported
      osteoclastogenesis but the osteoclast supporting capacity of osteogenically
      differentiated MSC decreased as compared with undifferentiated MSC. More
      interestingly, the adipogenically differentiated MSC significantly promoted
      osteoclasts formation when co-cultured with monocytes. It is concluded that the
      regulatory effect of MSC on osteoclast formation has changed while they have
      differentiated into different types of cells. The findings indicate that MSC may
      exert alternative effect on osteoclastogenesis by differentiation to descendant
      cells.

PMID- 23114146
TI  - [Dexamethasone impairs immunosuppressive ability of mesenchymal stem cells].
AB  - This study was aimed to investigate the effect of dexamethasone (Dex) on
      immunosuppressive ability of mesenchymal stem cells (MSC) during expansion and
      differentiation of MSC. MSC were cultured in 96-well flat-bottom plates.
      Proliferation assays were performed by using the BrdU colorimetric ELISA Kit. To
      explore the effect of Dex on MSC immunosuppressive ability, MSC were firstly
      cultured in complete culture medium for 14 d with Dex (10 nmol/L), and then,
      peripheral blood mononuclear cells (PBMNC) were co-cultured with MSC in 96-well
      flat-bottom plates for 3 d. Phytohemagglutinin A (PHA, 10 ug/ml) was used to
      stimulate activation of PBMNC. The concentrations of IFN-gamma in culture
      supernatants was detected by ELISA. The results indicated that there was no
      obvious difference in representative phenotypes of MSC between experimental and
      control groups after MSC were treated with low concentration of Dex (10 nmol/L)
      for 14 d, but the suppression of Dex-treated MSC on lymphocyte activation in same
      concentration of cells was significantly reduced as compared with control group.
      After the Dex-treated MSC were co-cultured with IFN-gamma for 12 h, the
      immunoregulatory ability of MSC was recovered in a certain degree. It is
      concluded that the Dex impairs the immunosuppressive ability of MSC, the IFN
      gamma can protect and reverse the immunosuppressive ability of MSC impaired by
      Dex, so that, when the immunoregulatory activity of MSC is investigated, it is
      necessary to avoid adding Dex in the culture medium.

PMID- 23114147
TI  - [Effects of interferon-gamma on expression of adhesion molecules in human
      umbilical cord mesenchymal stromal cells].
AB  - This study was purposed to investigate the effects of interferon (IFN)-gamma on
      expression of adhesion molecules in mesenchymal stromal cells derived from human
      umbilical cord tissue (UC-MSC). The UC-MSC were isolated from human umbilical
      cord by tissue culture. The expressions of specific markers on UC-MSC were
      detected by flow cytometry in the physiological condition. The adipogenic and
      osteogenic induction of UC-MSC was detected by alizarin and Oil red O staining.
      UC-MSC were exposed to IFN-gamma (100, 1 000, 10 000 U/ml) for 24 h, the
      expressions of CD54, CD58, CD44, CD49d, CD62p, CD62L, CD102 and CD106 on cell
      surface were detected using flow cytometry. The results showed that in
      physiological condition, UC-MSC extremely low expressed CD102, CD106, CD62P,
      CD62L, while the expression of CD54 was relatively high (41.58 +/- 0.83)%. When
      stimulated by IFN-gamma, the expression of CD102, CD106, CD62P, CD62L increased
      slightly, but still low (< 5%), while CD54 and CD58 upregulated concentration
      dependently up to (59.66 +/- 1.36)% and (43.96 +/- 0.62)% respectively. The
      expression of CD49d upregulated to (51.33 +/- 0.74)% when UC-MSC exposed to IFN
      gamma 100 U/ml. CD44 increased to (73.22 +/- 1.93)% when UC-MSC exposed to IFN
      gamma 1 000 U/ml. It is concluded that IFN-gamma can elevate significantly the
      expression of CD54, CD49d, CD44 and CD58, but has no significant effect on CD102,
      CD106, CD62P and CD62L expression on the surface of UC-MSC.

PMID- 23114148
TI  - [A1381T and -1793G/C polymorphisms of vWF gene impact the plasma vWF levels in
      Yugur, Tibetan and Han nationalities of China].
AB  - The aim of this study was to investigate the similarities and differences of
      A1381T (rs216311) and -1793G/C (rs7966230) single nucleotide polymorphisms (SNP)
      in Chinese Yugur, Tibetan, and Han nationalities and their influence on plasma
      vWF concentration in order to explore the sensitivity of these 3 nationalities to
      vWF-related diseases. Peripheral venous blood was obtained from 322 Yugur, 399
      Tibetan, and 120 Han healthy people. The DNA were then extracted. vWF gene A1381T
      and -1793G/C polymorphisms were analyzed by the polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) and sequenced when it was
      necessary. The vWF:Ag level in plasma was determined by ELISA. The results showed
      that the genotype distribution of vWF gene at both A1381T and -1793G/C loci in
      Yugur, Tibetan and Han nationalities was different with statistically
      significance (P < 0.05). GG genotype of A1381T locus accounted for 69.9% in Yugur
      nationality, which was much higher than 56.6% and 53.3% in Tibetan and Han
      nationalities respectively(P < 0.01); AA genotype of A1381T locus expressed a low
      level of vWF in plasma. For the -1793G/C locus, the proportion of CG genotype in
      Yugur was much higher than that in Han, CC genotype expressed a high level of vWF
      in plasma. The plasma vWF levels with different nationalities and the
      polymorphism of vWF gene were significantly different. It is concluded that the
      polymorphisms of vWF gene at both A1381T and -1793G/C loci in Yugur, Tibetan and
      Han are significantly different; the polymorphism of vWF gene influences the
      plasma vWF level; the plasma vWF levels in Yugur and Tibetan are significantly
      higher than that in Han, which may be associated with the living environment and
      habits.

PMID- 23114149
TI  - [Effects of ICAM-1 gene K469E, K56M polymorphisms on plasma sICAM-1 expression
      levels in Chinese Yugur, Tibetan and Han nationalities].
AB  - This study was purposed to investigate the intercellular cell adhesion molecule-1
      (ICAM-1) gene K469E (A/G) (rs5498) and K56M (A/T) (rs5491) single nucleotide
      polymorphisms (SNP) and soluble ICAM-1 (sICAM-1) levels in plasma in three
      Chinese populations of Yugur, Tibetan and Han nationalities, to analyze
      comparatively the genotypes and allele frequencies distribution in different
      ethnic groups, and to explore the effects of ICAM-1 K469E and K56M polymorphism
      and sICAM-1 levels in plasma. EDTA-anticoagulant venous blood from Yugur(327
      cases), Tibetan (400 cases) and Han (126 cases) people was collected, the DNA was
      extracted by using whole blood genomic DNA extraction kit, DNA SNP were analyzed
      by PCR-RFLP, genotype was judged by gel scan imaging system after agarose gel
      electrophoresis, the gene sequence was determined and the distribution of ICAM-1
      genotypes and allele frequencies were compared among different ethnic groups,
      besides, the group representativeness was tested via the Hardy-Weinberg genetic
      equilibrium. Finally, the human sICAM-1 plasma levels were detected by using
      human ICAM-1 ELISA kit. The results showed that DNA sequencing result was
      consistent with PCR-RFLP analysis. In Yugur, Tibetan and Han nationalities, the
      KK, KE and EE three genotypes at ICAM-1 K469E gene locus were detected, the
      genotype distribution was not statistically significantly different, while the K,
      E allele frequency distribution was statistically significantly different (P <
      0.05). Both of genotype and allele frequency distribution between Yugur, Tibetan
      and Han nationalities were statistically significantly different (P < 0.05). In
      K56M site only KK, KM two genotypes were detected, but the MM genotype was not
      detected in the three ethnic groups; the difference of two genotypes and K, M
      allele frequencies between Yugur and Han population was statistically
      significantly different (P < 0.05). Among three ethnic groups, the sex ratio and
      age distribution of K469E, K56M genotypes and allele frequencies of ICAM-1 gene
      were not significantly different, and distribution was in accordance with Hardy
      Weinberg genetic equilibrium (P > 0.05). The plasma sICAM-1 level at ICAM-1 K469E
      allele locus in K individuals [(253 +/- 122), (185 +/- 97) ug/L] was higher than
      that at non-K allele [(145 +/- 110) ug/L, P < 0.01]; the plasma sICAM-1 level of
      ICAM-1 K56M sites with KK genotype [(253 +/- 122) ug/L] was higher than that of
      the KM genotypes [(168 +/- 103) ug/L, P < 0.01]. In Yugur and Tibetan groups, the
      plasma sICAM-1 levels [(224 +/- 80), (214 +/- 111) ug/L] were higher than that in
      the Han group [(175 +/- 125)ug/L, P < 0.05]. Pairwise comparison indicated that
      the plasma sICAM-1 levels between Yugur and Han group were statistically
      significantly different (P < 0.01), that was significantly different between
      Tibetan and Han group (P < 0.05). It is concluded that in Yugur, Tibetan and Han
      population, the genotypes and gene frequencies of two amino acid sites K469E and
      K56M in ICAM-1 were KK/KE-type, KK-type and K allele, moreover, the ratio of them
      in Yugur and Tibetan group was higher than that in Han, while there is not
      significant difference in sex ratio and age distribution, therefore, ICAM-1
      genotype and allele frequency distribution in this study had ethnic
      representativeness. ICAM-1 gene K469E and K56M polymorphisms were likely to
      affect the plasma sICAM-1 expression level. K469E gene K allele may be a genetic
      risk factor, while K56M gene M allele a may be genetic protective factor for some
      diseases.

PMID- 23114150
TI  - [Cordyceps sinensis enhances lymphocyte proliferation and CD markers expression
      in simulated microgravity environment].
AB  - This study was aimed to explore the effect of cordyceps sinensis enhancing
      lymphocyte proliferation and surface CD marker expression in simulated
      microgravity environment. The splenic lymphocytes were separated from mice and
      cultured in the rotary cell culture system simulated microgravity environment.
      The cells were treated with different concentration of cordyceps sinensis
      solution (0, 6.25, 12.5, 25 and 50 ug/ml) for 24, 48 and 72 h respectively, then
      the cells were harvested, and analyzed for cell proliferation and the expression
      of cell surface markers (CD4 and CD8). The results showed that under simulated
      microgravity environment, the lymphocyte proliferation was inhibited. When the
      concentration of cordyceps sinensis was 25 or 50 ug/ml, the lymphocyte
      proliferation, CD4 and CD8 expressions all increased, but 50 ug/ml cordyceps
      sinensis could inhibit the proliferation ability with the time prolonging. It is
      concluded that the suitable concentration of cordyceps sinensis displayed the
      ability to enhance the lymphocyte proliferation and CD marker expression in
      simulated microgravity environment. These results may be valuable for screening
      drugs which can be potentially against immunosuppression under simulated
      microgravity.

PMID- 23114151
TI  - [Characteristics of cytogenetics and molecular biology in patients with
      eosinophilia].
AB  - The aim of study is to explore the characteristics of cytogenetics and molecular
      biology in patients with eosinophilia. Bone marrow samples from 79 cases of
      eosinophilia (AEoC >= 1.5*10(9)/L) were detected for PDGFRA/B and FGFR1 gene
      rearrangement by fluorescence in situ hybridization and reverse transcription
      polymerase chain reaction (RT-PCR). Forty-four samples were detected for T cell
      receptor (TCR) clonal rearrangement by PCR. The results showed that among 76
      cases the FIP1L1/PDGFRA (F/P) fusion gene was detected in 19 cases, the CHIC2
      deletion was detected in 19 cases, the PDGFRA rearrangement was detected in 4
      cases, and no FIP1L1 rearrangement was detected. According to the 2008 WHO
      classification, diagnosis were revised as myeloid neoplasms with PDGFRA/B
      rearrangement in 20 (42%) of 48 patients and 5 (83%) of 6 patients with
      hypereosinophilia syndrome (HES) or chronic eosinophilic leukemia (CEL),
      respectively. The diagnosis in (17%) of 6 patients with CEL was revised as
      chronic eosinophilic leukemia, not otherwise as specified (CEL-NOS). Clonal
      cytogenetic abnormalities were detected in 1 case of CEL-NOS and 3 cases with
      PDGFRB rearrangement. Karyotypic abnormalities involved in chromosome 4q12 were
      not detected in all of the 21 cases with PDGFRA rearrangement. The clonal TCR
      gene rearrangement were detected in 33% (5/15), 40% (6/15), and 36% (5/14) cases
      with PDGFRA/B rearrangement, HES, or secondary eosinophilia, respectively. There
      was no statistical difference in incidence rate among 3 subgroups. It is
      concluded that PDGFRA/B rearrangement can be detected in many cases of HES or
      CEL. Interphase FISH and PCR testing can enhance the diagnostic rate of myeloid
      neoplasms with PDGFRA/B rearrangement.

PMID- 23114152
TI  - [Diagnosis and treatment procedures of congenital neutropenia].
AB  - To explore the reasonable procedures and strategies of diagnosis and treatment of
      congenital neutropenia (CN), clinical data and laboratory examination results of
      a boy suspected of CN were collected; gene ELA2, GFI1, HAX1, and WASp of whom
      were sequenced, granulocyte colony-stimulating factor receptor (G-CSFR)
      expression on neutrophil was analyzed, and cytoplasmic domain of G-CSFR was
      sequenced. The results showed that the diagnosis of non-syndromic variants of CN
      (NSVCN) was made on this patient according to the criteria; sequencing results
      revealed no mutation occurred in ELA2, GFI1, HAX1 and WASp; a normal expression
      level of G-CSFR on neutrophil from this patient was detected and no truncated
      mutation was found in the intracellular domain of G-CSFR. It is concluded that
      reasonable procedure of diagnosis and treatment of CN is established, and a
      sporadic NSVCN with no recognized pathogenic mutation is confirmed in this
      patient.

PMID- 23114153
TI  - [Quantitative PCR for early diagnosis of invasive fungal infections in patients
      with hematologic malignancies].
AB  - This study was aimed to establish the approach of quantitative PCR (q-PCR) for
      diagnosis of invasive fungal infections (IFI) in patients with hematologic
      malignancies. Specimens from 40 patients with hematologic malignancies were
      chosen for q-PCR and galactomannan (GM) test. The 28S rRNA, a real high consensus
      sequence of fungi, was selected as target gene to design primer and probe. The
      DNA of fungal species was extracted from serum specimens. The results showed that
      q-PCR sensitivity, specificity, positive and negative predictive values were
      0.89, 0.85, 0.89, 0.85 respectively; GM test sensitivity, specificity, positive
      and negative predictive values were 0.83, 0.80, 0.88, 0.73 respectively; as
      combined q-PCR with GM test, these values were 0.94, 0.85, 0.89, 0.92
      respectively. It is concluded that the q-PCR assay can be used for early
      diagnosis for IFI in patients with hematologic malignancies, q-PCR combined with
      GM test can enhance the diagnosis sensitivity for IFI.

PMID- 23114154
TI  - [Removal of alphaGal xenotransplantation antigen by a novel alpha-galactosidase].
AB  - alphaGal, a xenotransplantations antigen (XTA), can lead to hyper acute reaction
      (HAR) in xenotransplantation. alpha-Galactosidase from B. fragilis is a novel
      galactosidase belong to CAZy GH110 which can clear the terminal alphaGal from
      branched and linear oligosaccharides. This study was purposed to investigate the
      removal effect of a novel alpha-galactosidase on alpha-Gal XTA on surface of red
      blood cells. The alphaGal XTA from the red blood cells of cattle, pig, dog and
      rabbit was digested by using recombinant alpha-galactosidase; the alpha-Gal
      antigens on surface of cells was detected by flow cytometry. The results showed
      that the XTA was disappeared completely or mainly. It is concluded that the novel
      alpha-galactosidase is a potential enzyme to remove the XTA on the surface of
      xenotransplants and can be used to overcome the HAR in xenotransplantation.

PMID- 23114155
TI  - [Genetic polymorphism of human platelet antigens 1-18 in Chinese Nanjing Han
      population].
AB  - The purpose of this study was to investigate the allele frequencies of the human
      platelet alloantigens 1-18 system (HPA-1-18) in Chinese Nanjing unrelated and
      healthy Han population, so as to provide the credible basis to screen compatible
      platelets for transfusing patients. The genotypes of 18 HPA systems were
      determined by polymerase chain reaction using sequence-specific primer (PCR-SSP)
      for 300 samples. The results showed that the gene frequencies obtained from 300
      Nanjing unrelated population were 0.9183 and 0.0817 for HPA-2a and -2b, 0.6100
      and 0.3900 for HPA-3a and -3b, 0.9733 and 0.0267 for HPA-5a and -5b, 0.9883 and
      0.0117 for HPA-6a and -6b, 0.5250 and 0.4750 for HPA-15a and -15b. All the tested
      individuals were homozygotes for HPA-1a, -4a, -7a-14a and HPA -16a-18a. There was
      a good fit to Hardy-Weinberg equilibrium in each group. It is concluded that this
      study has confirmed the ethnic and regional difference of HPA, and HPA in Nanjing
      Han population has its own characteristics. The highest heterozygotes are HPA-3
      and HPA-15, thus more attention to HPA effects on clinical platelet matched
      transfusion should be paid.

PMID- 23114156
TI  - [Correlation of hemogram changes during pregnancy of healthy women with
      postpartum blood transfusion].
AB  - This study was aimed to explore the correlation of hemogram changes during
      pregnancy of healthy women with postpartum blood transfusion. The outpatient and
      inpatient information of expectant lying-in women in our hospitals was collected,
      the route blood test, lever and kidney function and blood coagulation function
      tests were performed from the 4th to the 10th month of pregnancy. The pregnant
      women without underlying diseases and non-elderly pregnant women with single
      fetus were selected as the subjects of study. They were divided into postpartum
      blood transfusion group and non-blood transfusion group. The white blood cell
      (WBC) count, hemoglobin (Hb) level, platelet (Plt) count, plateletocrit (PCT),
      mean platelet volume (MPV), platelet distribution width (PDW) were compared in 2
      groups. The results showed that 68 cases out of 450 expectant lying-in women
      received blood transfusion, among them 30 cases with complete data of puerperal
      transfusion were taken as blood transfusion group, the 28 cases of non
      transfusion puerperal as control group. There was no significant difference of
      hemogram changes between the two groups. However, there was a slight decline in
      Plt count and Hb level of late pregnant women. What is more, there was no
      correlation between Plt count change and the PCT, MPV and PDW. It is concluded
      that the changes of hemogram during pregnancy has no correlation with postpartum
      hemorrhage and blood transfusion in healthy pregnant women, the Plt count and Hb
      level of pregnant women slightly decline. Nevertheless, PCT, MPV and PDW are
      within the normal range.

PMID- 23114157
TI  - [Discovery of a novel A2 allel in ABO blood group system and investigation of its
      distribution in Han population of Chinese Fujian province].
AB  - This study was aimed to investigate the distribution of A2 subgroup in Han
      Population of Chinese Fujian province and its molecular mechanisms. One
      individual with serologic ABO blood grouping discrepancy was identified with
      commercially available monoclonal and polyclonal antibodies and lectin: anti-A,
      anti-B, anti-AB, anti-A1, and anti-H reagents according to the routine laboratory
      methods. DNA sequences of exon 6, 7 and intron 6 of ABO gene were analyzed by
      polymerase chain reaction using genomic DNA and direct DNA sequencing or
      sequencing after gene cloning. Red cells of 3 176 A or AB unrelated individuals
      were tested with anti-A1. The results showed that this individual was identified
      as A2 subgroup by serological technology, sequencing analysis indicated the A2
      subgroup with novel A variant allele, the novel A allele being different from the
      allele A101 by 467C > T and 607G > A missense mutation in exon 7, no A2 subgroup
      was identified from the 3 176 individuals by using standard serological
      technology. It is concluded that a novel A allele responsible for A2 subgroup
      composing of 467C > T and 607G > A has been firstly confirmed, and the A2
      subgroup is very rare in Chinese Fujian Han population.

PMID- 23114158
TI  - [Research advance of hematopoietic microenvironment for myelodysplastic
      syndromes].
AB  - Myelodysplastic syndrome (MDS) is a group of heterogeneous clonal diseases
      characterized by ineffective hematopoiesis, peripheral blood cytopenias and high
      risk of transformation to acute myeloid leukemia.Recently more and more
      investigations indicate that the abnormality of bone marrow microenvironment is
      one of important reasons related to MDS. In this article the abnormality of
      stroma cells, cytokines and signaling pathways in hematopoietic micro-environment
      of MDS is reviewed.

PMID- 23114159
TI  - [Detection of abnormal plasma cells in bone marrow contributes to the diagnosis
      of primary systemic light chain amyloidosis-review].
AB  - Primary systemic light chain amyloidosis or immunoglobulin light-chain
      amyloidosis (AL) is the most common type of systemic amyloidosis.AL is a
      proteotoxic clonal plasma cell disease, a hematological malignancy, characterised
      by overproduction of immunoglobulin light chains that form characteristic
      abnormally folded and aggregated, insoluble fibrillar deposits in various organs,
      including kidneys, heart, liver, and autonomic and peripheral nerves, etc, these
      processes lead to organ dysfunction and death. Systemic amyloidosis have various
      types with different causes, thereby its clinical diagnosis and treatment are
      more difficult. Recent developments on studies that have significantly aided the
      management of patients with AL include diagnostic techniques for definitive
      typing of amyloid deposits by using flow cytometry and immunophenotype analysis.
      These methods can detect abnormalities of bone marrow plasma cell clones, such as
      CD38(+), CD138(+), CD56(+), CD19(-) in AL patients. The monitoring abnormal
      plasma cells with immunoglobulin light chain restriction and abnormal plasma cell
      phenotypic characteristics contributes to the early diagnosis of AL and detection
      of minimal residual disease after treatment, which greatly improved AL treatment
      and prognosis. In this review the diagnosis and typing, clinical characteristics,
      flow cytometry, immunophenotyping of bone marrow cells, immunoglobulin light
      chain restriction and phenotypic characteristics of abnormal plasma cells of AL
      are briefly summarized.

PMID- 23114160
TI  - [Roles of CEBPA mutation and expression abnormality in acute myeloid leukemia -
      review].
AB  - CCAAT enhancer binding protein A (CEBPA) and its product transcription factor
      CCAAT enhancer binding protein alpha (C/EBPalpha) play pivotal roles in early
      granulocyte development. C/EBPalpha induces the transition and keeps the balance
      of differentiation and proliferation of myeloid progenitors. The mutation and
      dysregulation of CEBPA at transcription, translation or post-translation level
      lead to differentiation block and over proliferation of immature hematopoietic
      cells, which are important mechanisms of acute myeloid leukemia (AML). The
      mutation and dysregulation of CEBPA also provide clues for evaluating the outcome
      of AML patients and potential targets for differentiation-inducing therapies.
      This review focus on CEBPA mutation and AML, dysregulation of C/EBPalpha protein
      expression and AML, as well as C/EBPalpha protein and targeting therapy.

PMID- 23114161
TI  - [Research advances of extramedullary relapse in multiple myeloma - review].
AB  - Multiple myeloma (MM) is a malignant plasma cell disorder characterized by the
      abnormal expansion and accumulation of clonal plasma cells in the bone marrow in
      association with production of monoclonal immunoglobulin and its fragment (as
      protein), and MM remains an incurable disease. Recently extramedullary relapse of
      MM is more frequent especially in patients treated with stem cell transplantation
      and/or novel drugs. This review focuses the incidence of extramedullary relapse
      in MM, mechanisms involved in extramedullary myeloma spread, tumor
      characteristics at extramedullary sites as well as prognosis and response to
      therapy.

PMID- 23114162
TI  - [Advancements in diagnosis and management of paroxysmal nocturnal hemoglobinuria 
      review].
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is a hemolytic disease of abnormally
      activated complement. FLAER diagnosis is a higher sensitive and specific method,
      which makes PNH patients to be early discovered and treated. Non-typical symptoms
      including thrombosis, pulmonary hypertension and chronic kidney disease in PNH
      have been caused increasing attention. Eculizumab monoclonal antibody has greatly
      improved the current treatment status of PNH. PNH can be cured thoroughly by
      allogeneic hematopoietic stem cell transplantation. In this article, the FLAER
      diagnosis, clinic symptoms and progress of treatment in patients with PNH are
      reviewed.

PMID- 23114163
TI  - [Research progress in MDS mouse model- review].
AB  - Myelodysplastic syndromes (MDS) are hematopoietic malignancies characterized by
      peripheral cytopenia and dysplastic bone marrow that arise from mutations in the
      hematopoietic stem/progenitor cells (HSPC). Recently, significant effects have
      been made to develop appropriate mouse models to study this complex disease.
      Three general approaches have been used to establish the MDS mouse, including
      treatment with mutagens or carcinogen, xenotransplantation of human MDS cells,
      and genetic engineering of mouse hematopoietic cells. In this review, several MDS
      mouse models and the advances of study on the mechanisms of malignant clone and
      the marrow microenvironment are summarized. In addition, the progress in
      xenotransplantation models of MDS and the problems to be solved are discussed
      briefly.

PMID- 23114164
TI  - [Research advances on correlation of ARID5B gene with childhood acute
      lymphoblastic leukemia - review].
AB  - Childhood acute lymphoblastic leukemia (C-ALL) is the most common pediatric
      cancer. Although its etiology remains poorly understood, the hypothesis of ALL
      correlated with a genetic basis was examined through association studies based on
      candidate genes. Recently, two independent large-scale genome-wide association
      studies reported that the five single nucleotide polymorphisms (rs7073837;
      rs10821936; rs10994982; rs7089424; rs10740055) in the gene AT rich interactive
      domain 5B (ARID5B) at 10q21.2, were associated with the high incidence risk of C
      ALL, especially with hyperdiploid lymphoblastic leukemia. Variations in these
      single nucleotide polymorphisms influence the risk of specific disease subtypes,
      and also possess race- and sex-differences in leukemia incidence. Further
      elucidation of the mechanisms through which ARID5B variants are involved in C-ALL
      not only has a great diagnostic value, but also a guidance for the clinical
      therapy, ultimately improving the prognosis of disease. Therefore, the related
      studies of ARID5B with C-ALL were summarized briefly in this review.

PMID- 23114165
TI  - [Reactive oxygen species and fibrosis in tissues and organs - review].
AB  - Reactive oxygen species (ROS) is a kind of molecules derived by oxygen in the
      metabolic process of aerobic cells, which mainly includes superoxide, hydroxyl
      radicals, alkoxyl, hydrogen peroxide, hypochlorous acid, ozone, etc. They can
      destroy the structure and function of cells through the damage of biological
      macromolecules such as DNA, proteins and the lipid peroxidation. ROS also can
      regulate the proliferation, differentiation and apoptosis of cells through
      several signaling pathways and participate in fibrogenesis of many organs
      including hepatic and pulmonary fibrosis. Recent study shows that ROS might have
      an important effect on the forming of myelofibrosis. Consequently, ROS plays a
      significant role in the fibrogenesis of tissues and organs. In this review, the
      relevance between ROS and common tissues and organs fibrosis is summarized.

PMID- 23114166
TI  - [Therapeutics of Burkitt lymphoma in adults - review].
AB  - Burkitt lymphoma is a highly aggressive non-Hodgkin's lymphoma. As Burkitt
      lymphoma cells are very sensitive to chemotherapy, chemotherapy is the major
      therapeutic schedule for this disease. Rituximab raised the overall survival rate
      markedly. Bone marrow transplant, surgery and radiotherapy also demonstrated to
      have a supporting role for patients with Burkitt lymphoma. This review focus on
      research progress of the therapeutics and major regimens for the disease.

PMID- 23114167
TI  - Characterizing the EPODE logic model: unravelling the past and informing the
      future.
AB  - EPODE ('Ensemble Prevenons l'Obesite De Enfants' or 'Together let's Prevent
      Childhood Obesity') is a large-scale, centrally coordinated, capacity-building
      approach for communities to implement effective and sustainable strategies to
      prevent childhood obesity. Since 2004, EPODE has been implemented in over 500
      communities in six countries. Although based on emergent practice and scientific
      knowledge, EPODE, as many community programs, lacks a logic model depicting key
      elements of the approach. The objective of this study is to gain insight in the
      dynamics and key elements of EPODE and to represent these in a schematic logic
      model. EPODE's process manuals and documents were collected and interviews were
      held with professionals involved in the planning and delivery of EPODE. Retrieved
      data were coded, themed and placed in a four-level logic model. With input from
      international experts, this model was scaled down to a concise logic model
      covering four critical components: political commitment, public and private
      partnerships, social marketing and evaluation. The EPODE logic model presented
      here can be used as a reference for future and follow-up research; to support
      future implementation of EPODE in communities; as a tool in the engagement of
      stakeholders; and to guide the construction of a locally tailored evaluation
      plan.

PMID- 23114168
TI  - [A neonate with subumbilical swellings].
AB  - A neonate presented with hypoplasia of the abdominal wall muscles after fetal
      ascites due to anemia caused by an intra-uterine infection with parvovirus B19.
      Because this is an extremely rare complication, pathogenesis and prognosis are
      currently unclear.

PMID- 23114169
TI  - [Pancreatoduodenectomy for suspected malignancy: indications, complications and
      survival].
AB  - OBJECTIVE: To evaluate the indications, complications and survival after
      pancreatoduodenectomy, with special attention for the outcome after extended
      resection due to tumour extension and in elderly patients. DESIGN: Retrospective,
      partly cross-sectional study. METHOD: All 275 consecutive adult patients who
      underwent explorative laparotomy for a suspected resectable pancreatic head
      tumour or periampulary tumour in two Dutch tertiary centres between 2007 and 2010
      were included. We graded the postoperative complications according to
      international classifications and collected data on survival. RESULTS: In 218/275
      patients (79%) the tumour could be resected by pancreatoduodenectomy with or
      without an extended resection. Malignancy was confirmed in 190/218 patients
      (87%); in 153/190 patients (81%) a microscopically radical (R0) resection was
      achieved. Fifteen percent of the patients required a re-intervention
      (radiological, endoscopic or surgical) because of an intra-abdominal
      complication. The post-operative 30-day mortality was 4.1%. Eighty-six patients
      (39%) were ultimately diagnosed with 'pancreatic adenocarcinoma'; they had a 1-
      and 2-year survival rate of 63% and 34%, respectively. In 27 patients (12%) who
      underwent an extended resection for oncological reasons, such as partial hepatic
      portal vein resection, the 30-day mortality was 0% and the survival rates were
      comparable to patients with a standard resection. The 81 patients (37%) aged 70
      or older had a 30-day mortality and survival similar to younger patients.
      CONCLUSION: More than 75% of potentially resectable tumours were resected by a
      pancreatoduodenectomy with or without an extended resection, with a relatively
      low postoperative mortality and an adequate survival benefit. After
      multidisciplinary assessment, both limited tumour extension and a higher age are
      not necessarily contraindications for a resection, as a comparable survival
      benefit can be obtained for these groups of patients as for other groups.

PMID- 23114170
TI  - [Erectile dysfunction and incontinence after prostatectomy. Treating the
      complications of surgery for prostate cancer].
AB  - After having undergone a radical prostatectomy, 1 out of 5 men is dissatisfied
      about the functional results particularly because of complications like erectile
      dysfunction and urinary incontinence; these complications frequently do occur.
      During the first postoperative year, patient counselling and guidance are
      necessary aspects of the management of urinary incontinence and erectile
      dysfunction. In order to prevent irreversible erectile dysfunction, it is
      important that the patient resumes sexual activity soon after the operation; if
      necessary, a phosphodiesterase-5 (PDE-5) inhibitor or intracavernosal injection
      therapy may be used. Treatment of urinary incontinence in the first postoperative
      year consists of pelvic floor exercises and guidance on the use of collection
      devices, penile clamps or condom catheters. If urogenital functional disorders
      persist after one year, in a way that significantly affects patient's quality of
      life, the implantation of an erectile prosthesis or - depending on the amount of
      urine loss - a sling or sphincter prosthesis is indicated.

PMID- 23114172
TI  - [Pulmonary toxicity resulting from the use of nitrofurantoin].
AB  - Acute pulmonary syndrome is an uncommon but severe adverse reaction to
      nitrofurantoin. This syndrome is seldom recognised at the moment of presentation,
      which potentially subjects patients to unnecessary treatment and delays in the
      discontinuation of nitrofurantoin. We discuss the case histories of an 80-year
      old and an 81-year-old woman, each presenting with acute pulmonary syndrome after
      nitrofurantoin administration. The diagnosis of acute pulmonary syndrome should
      be considered in patients presenting with fever, dyspnoea, dry cough,
      leukocytosis (typically with eosinophilia) and a bilateral interstitial pattern
      visible on the chest X-ray after having started nitrofurantoin. The prognosis is
      excellent if the condition is recognised early and the exposure to nitrofurantoin
      is discontinued.

PMID- 23114171
TI  - [Prevention of severe infections in patients with hyposplenism or asplenia].
AB  - Each year, up to a 1000 splenectomies are performed in the Netherlands. Aside
      from patients without a spleen, there is also a large group of patients with
      hyposplenism or functional asplenia due to other primary diseases. All these
      patients are at risk of developing severe infections, such as post-splenectomy
      sepsis (PSS), which is associated with very high mortality. However PSS can
      partly be prevented by taking simple measures such as immunizations and
      prophylactic or early use of antibiotics. Healthcare professionals in first and
      secondary care in the Netherlands are generally not well informed about which
      preventive measures should be taken to prevent these infections, resulting in
      often suboptimal management of patients. In this article, recommendations are
      given on vaccination and administration of antibiotics to prevent severe
      infections such as PSS in this group of patients.

PMID- 23114173
TI  - [Streptococcus suis meningitis in a meat factory employee].
AB  - BACKGROUND: In the Netherlands, Streptococcus suis is a rare cause of meningitis.
      Over the past few years, the number of reported cases worldwide has increased.
      The bacterium is mainly isolated in pigs, but humans can also become infected.
      CASE DESCRIPTION: At the Emergency Department, a 60-year-old man presented with
      headache, confusion, fever and nuchal rigidity. He worked at a meat factory.
      Laboratory testing showed abnormalities linked to bacterial meningitis. S. suis
      was cultured from blood and cerebrospinal fluid. The patient was treated with
      dexamethasone, ceftriaxone and later benzylpenicillin intravenously. He recovered
      well, but had bilateral perceptive hearing loss as a sequela. CONCLUSION:
      Particularly people who are in close contact with pigs have an increased risk of
      S. suis infection. S. suis meningitis can be very severe and lead to serious
      complications and even death. Rapid diagnosis and adequate treatment are
      critical. Permanent hearing loss is the most frequent sequela.

PMID- 23114174
TI  - [Fatal respiratory failure in a morbidly obese patient].
AB  - BACKGROUND: Healthcare professionals are seeing an increasing number of morbidly
      obese patients. Medical interventions are often difficult to perform in these
      patients. In acute situations this can lead to major problems. CASE DESCRIPTION:
      Assistance from a mobile medical team was requested for a 42-year-old male
      weighing 350 kg with severe respiratory failure. Transporting the patient was
      problematic due to his build. The hospital to which he was brought after hours of
      delay lacked the appropriate space and resources for morbidly obese patients.
      Since the condition of the patient deteriorated, intubation and mechanical
      ventilation were required. Despite additional equipments for problematic airway
      access, the procedure failed and the patient died due to respiratory failure.
      CONCLUSION: Designating centres for care, also in the acute situations, of
      morbidly obese patients is recommended, to improve the care of these patients and
      to prevent disasters.

PMID- 23114175
TI  - [Patients from high-risk regions infected with HIV: recognition can prevent
      serious complications].
AB  - A 46-year-old woman and a 39-year-old male, both of African origin, consulted the
      general practitioner because of back pain and blurry vision, respectively. After
      several months of diagnostic delay, the woman was diagnosed with a diffuse large
      B-cell lymphoma and the man with progressive multifocal leukoencephalopathy, each
      secondary to a chronic HIV infection. In retrospect, both patients' medical
      histories and physical examinations had revealed signs and symptoms of an HIV
      infection. Since the prevalence of HIV is high in many African countries, one
      should be highly suspicious of possible infection with HIV, even when a patient
      presents with everyday complaints; patients originating from high-risk areas in
      particular should be tested for HIV. Careful history-taking and a thorough
      physical examination can be helpful in collecting diagnostic clues pointing
      towards HIV.

PMID- 23114177
TI  - [The hybrid operating room: a cross between a catheterisation room and an
      operating room].
AB  - A hybrid operating room is a space that meets all the stringent requirements of
      an operating room harbouring the facilities of an interventional radiology or
      cardiology room. This technical innovation facilitates complex endovascular and
      hybrid operations in a sterile environment. The high-end imaging technique with
      the ability to perform three-dimensional reconstructions will lead to improved
      quality of endovascular operations. Moreover, this technique enables physicians
      to explore and extend the boundaries not only of cardiovascular but also of
      navigated minimally invasive surgical techniques.

PMID- 23114178
TI  - [Skin tumours underexposed in general practice].
AB  - General practitioners (GPs) in the Netherlands frequently assess skin tumours
      such as moles. However, the training of medical students, GP trainees and
      postgraduate training of GPs in evaluating these skin lesions is limited.
      Furthermore, literature is scarce and no guidelines are available. It is still
      unclear when histopathological evaluation of an excised skin lesion should be
      performed. Additional research in primary care populations and the development of
      a guideline would promote a more unambiguous approach. More (postgraduate)
      education is needed on this topic. Dermatoscopy and teledermatology might also
      play a role in improving care.

PMID- 23114179
TI  - [Summary of the Dutch College of General Practitioners' (NHG) practice guideline
      'The menopausal transition'].
AB  - The Dutch College of General Practitioners' (NHG) practice guideline 'The
      menopausal transition' provides general practitioners with guidelines for the
      management of menopausal symptoms in women from the age of 40 years. Patient
      history is vital in determining and assessing menopausal symptoms. Patient
      education is often sufficient to help women cope with their menopausal symptoms;
      medication is seldom required. Most systemic hormonal preparations increase the
      risk of venous thromboembolism, cardiovascular disease and breast cancer; these
      are therefore only indicated if vasomotor symptoms lead to serious limitations in
      daily life. Before the patient is given hormonal therapy, the cardiovascular risk
      profile and risk of venous thromboembolism and breast cancer should be assessed.
      Local hormonal treatment can be indicated for vaginal symptoms.

PMID- 23114180
TI  - Standards for foundation trust status will not be lowered even if trusts fail the
      test, says Monitor.

PMID- 23114181
TI  - A perspective on the interfacial properties of nanoscopic liquid drops.
AB  - The structural and interfacial properties of nanoscopic liquid drops are assessed
      by means of mechanical, thermodynamical, and statistical mechanical approaches
      that are discussed in detail, including original developments at both the
      macroscopic level and the microscopic level of density functional theory (DFT).
      With a novel analysis we show that a purely macroscopic (static) mechanical
      treatment can lead to a qualitatively reasonable description of the surface
      tension and the Tolman length of a liquid drop; the latter parameter, which
      characterizes the curvature dependence of the tension, is found to be negative
      and has a magnitude of about a half of the molecular dimension. A mechanical
      slant cannot, however, be considered satisfactory for small finite-size systems
      where fluctuation effects are significant. From the opposite perspective, a
      curvature expansion of the macroscopic thermodynamic properties (density and
      chemical potential) is then used to demonstrate that a purely thermodynamic
      approach of this type cannot in itself correctly account for the curvature
      correction of the surface tension of liquid drops. We emphasize that any
      approach, e.g., classical nucleation theory, which is based on a purely
      macroscopic viewpoint, does not lead to a reliable representation when the radius
      of the drop becomes microscopic. The description of the enhanced inhomogeneity
      exhibited by small drops (particularly in the dense interior) necessitates a
      treatment at the molecular level to account for finite-size and surface effects
      correctly. The so-called mechanical route, which corresponds to a molecular-level
      extension of the macroscopic theory of elasticity and is particularly popular in
      molecular dynamics simulation, also appears to be unreliable due to the inherent
      ambiguity in the definition of the microscopic pressure tensor, an observation
      which has been known for decades but is frequently ignored. The union of the
      theory of capillarity (developed in the nineteenth century by Gibbs and then
      promoted by Tolman) with a microscopic DFT treatment allows for a direct and
      unambiguous description of the interfacial properties of drops of arbitrary size;
      DFT provides all of the bulk and surface characteristics of the system that are
      required to uniquely define its thermodynamic properties. In this vein, we
      propose a non-local mean-field DFT for Lennard-Jones (LJ) fluids to examine drops
      of varying size. A comparison of the predictions of our DFT with recent
      simulation data based on a second-order fluctuation analysis (Sampayo et al 2010
      J. Chem. Phys. 132 141101) reveals the consistency of the two treatments. This
      observation highlights the significance of fluctuation effects in small drops,
      which give rise to additional entropic (thermal non-mechanical) contributions, in
      contrast to what one observes in the case of planar interfaces which are governed
      by the laws of mechanical equilibrium. A small negative Tolman length (which is
      found to be about a tenth of the molecular diameter) and a non-monotonic
      behaviour of the surface tension with the drop radius are predicted for the LJ
      fluid. Finally, the limits of the validity of the Tolman approach, the effect of
      the range of the intermolecular potential, and the behaviour of bubbles are
      briefly discussed.

PMID- 23114183
TI  - Collective dynamics in binary liquids: a molecular dynamics study of the
      composition dependence of the spectra of collective excitations.
AB  - The spectra of longitudinal and transverse collective excitations in liquid
      binary metallic Na(c)K(1-c) alloys are studied for pure components and four
      different concentrations. A theoretical generalized collective modes approach is
      used to analyze the concentration dependence of the dispersion of acoustic and
      optic branches in a wide region of wavenumbers. The dispersion of longitudinal
      collective excitations in binary alloys is estimated from the eight-variable
      thermo-viscoelastic dynamic model with full account of thermal fluctuations. It
      is found that the longitudinal and transverse branches show different dependences
      on concentration in the short-wavelength region. The issue of 'positive
      dispersion' of acoustic excitations in liquid binary alloys on the boundary of
      the hydrodynamic regime is discussed. It is shown that the coupling between
      longitudinal acoustic and optic modes is responsible for an increase of the
      'positive dispersion' close to equimolar composition.

PMID- 23114182
TI  - Salivary biomarker development using genomic, proteomic and metabolomic
      approaches.
AB  - The use of saliva as a diagnostic sample provides a non-invasive, cost-efficient
      method of sample collection for disease screening without the need for highly
      trained professionals. Saliva collection is far more practical and safe compared
      with invasive methods of sample collection, because of the infection risk from
      contaminated needles during, for example, blood sampling. Furthermore, the use of
      saliva could increase the availability of accurate diagnostics for remote and
      impoverished regions. However, the development of salivary diagnostics has
      required technical innovation to allow stabilization and detection of analytes in
      the complex molecular mixture that is saliva. The recent development of cost
      effective room temperature analyte stabilization methods, nucleic acid pre
      amplification techniques and direct saliva transcriptomic analysis have allowed
      accurate detection and quantification of transcripts found in saliva. Novel
      protein stabilization methods have also facilitated improved proteomic analyses.
      Although candidate biomarkers have been discovered using epigenetic,
      transcriptomic, proteomic and metabolomic approaches, transcriptomic analyses
      have so far achieved the most progress in terms of sensitivity and specificity,
      and progress towards clinical implementation. Here, we review recent developments
      in salivary diagnostics that have been accomplished using genomic,
      transcriptomic, proteomic and metabolomic approaches. 

PMID- 23114184
TI  - Comparing the reverse Trendelenburg and horizontal position for endoscopic sinus
      surgery: a randomized controlled trial.
AB  - OBJECTIVE: To determine whether the 15-degree reverse Trendelenburg position
      (RTP) during functional endoscopic sinus surgery improves endoscopic field of
      view and reduces intraoperative blood loss when compared with the horizontal
      position (HP). STUDY DESIGN: A prospective, randomized controlled trial. SETTING:
      St Paul's Sinus Centre, Vancouver, Canada. SUBJECTS: Patients with chronic
      rhinosinusitis (CRS), with or without nasal polyposis, receiving functional
      endoscopic sinus surgery were included. Patients were excluded if they had severe
      or uncontrolled hypertension and cardiovascular disease, continued use of
      anticoagulants, impaired coagulation, or a sinonasal tumor. METHODS: Sixty-four
      patients with CRS undergoing functional endoscopic sinus surgery (FESS) were
      randomized to either 15-degree RTP (experimental arm) or HP (control arm) from
      October 2011 to February 2012. Boezaart endoscopic field-of-view grading system
      was the primary outcome measure. Lund-Mackay computed tomography (CT) score,
      total blood loss, blood loss per minute, mean arterial pressure, heart rate,
      anesthetic technique, and surgery time were also recorded. RESULTS: There was a
      significant difference in mean Boezaart scoring between RTP and HP: 1.66 vs 2.33
      (P < .001), with RTP producing a better endoscopic field of view. There was also
      a lower total blood loss and blood loss per minute with RTP (P = .01, P = .03).
      There was no significant difference in disease severity (P > .05), time of
      surgery (P > .05), or mean arterial pressure (P > .05) between the 2 surgical
      positions. CONCLUSION: The 15-degree RTP improves the endoscopic field of view
      and reduces blood loss during FESS. We would therefore recommend its use.

PMID- 23114185
TI  - A controlled study to determine the efficacy of Loxostylis alata (Anacardiaceae)
      in the treatment of aspergillus in a chicken (Gallus domesticus) model in
      comparison to ketoconazole.
AB  - BACKGROUND: The poultry industry due to intensive methods of farming is burdened
      with losses from numerous infectious agents, of which one is the fungus
      Aspergillus fumigatus. In a preliminary study, the extracts of Loxostylis alata
      A. Spreng, ex Rchb. showed good activity in vitro against A. fumigatus with a
      minimum inhibitory concentration of 0.07 mg/ml. For this study crude, a crude
      acetone extract of L. alata leaves was evaluated for its acute toxicity in a
      healthy chicken model and for efficacy in an infectious model of aspergillosis
      (A. fumigatus). RESULTS: At a dose of 300 mg/kg, the extract induced some
      toxicity characterised by decreased feed intake and weight loss. Consequently,
      100 and 200 mg/kg were used to ascertain efficacy in the infectious model. The
      plant extract significantly reduced clinical disease in comparison to the control
      in a dose dependant manner. The extract was as effective as the positive control
      ketoconazole dosed at 60 mg/kg. CONCLUSIONS: The results indicate that a crude
      extract of L. alata leaves has potential as an antifungal agent to protect
      poultry against avian aspergillosis.

PMID- 23114186
TI  - The health of women in the US fire service.
AB  - BACKGROUND: Despite statements from national fire service organizations,
      including the International Association of Fire Fighters (IAFF) and the
      International Association of Fire Chiefs (IAFC), promoting a diverse work force
      related to gender within the fire service, rates of women firefighters remain
      very low. Thus, research into why this extensive gender disparity continues is a
      high priority. Recent years have seen a number of large scale studies on
      firefighter health and health risk behaviors however, none have focused on the
      health of women firefighters and nearly all have eliminated women from the sample
      due to small sample size. Data from the present report is drawn from all females
      in a large, randomly selected cohort of firefighters in an epidemiological study
      designed to assess health outcomes and health risk behaviors identified as most
      important to the fire service. METHODS: Data reported for the present study were
      collected as baseline data for the Firefighter Injury and Risk Evaluation (FIRE)
      Study, a longitudinal cohort study examining risk factors for injury in both
      career and volunteer firefighters in the IAFC Missouri Valley Region. Of the
      departments assessed, only 8 career and 6 volunteer departments had any women
      firefighters. All the women solicited for participation chose to enroll in the
      study. The number of women ranged from 1 to 7 in career departments and 1 to 6 in
      volunteer departments. RESULTS: Where possible, comparisons are made between
      female firefighters and published data on male firefighters as well as
      comparisons between female firefighters and military members. Compared to male
      firefighters, females had more favorable body composition among both career and
      volunteer firefighters. Tobacco use rates were generally higher among females
      than males and rates among female firefighters were similar to the rates of
      female military members. While rates of alcohol use were higher than the general
      population, only one of the participants evidenced responses in the range of
      concern on the CAGE screening. CONCLUSIONS: In general, the findings offer an
      interesting glimpse of the health of women in the fire service as a generally
      healthy occupational workforce with some unique health risk behavior challenges.
      They also highlight some of the similarities and differences between male and
      female firefighters and bolster the argument for studying female firefighters as
      a unique occupational sub-population.

PMID- 23114187
TI  - Alopecia areata as a complication of hair restoration surgery.

PMID- 23114188
TI  - Metastatic lobular carcinoma of the breast masquerading as a primary rectal
      cancer.
AB  - BACKGROUND: Colorectal metastasis of lobular carcinoma of the breast is a
      diagnostic challenge. It may macroscopically simulate primary colon cancer or
      inflammatory bowel disease. In some cases, the interval between the primary
      breast cancer and metastatic colorectal lesions is so long that the critical
      records for diagnosis including history might be lost or missed. CASE
      PRESENTATION: Reported herein is a case of metastatic lobular carcinoma of the
      breast masquerading as a primary rectal cancer developed in a 62-year-old
      Japanese woman. The case initially presented as a circumferential rectal lesion,
      and information on the patient's history of breast cancer was not noted. As the
      result of endoscopic biopsy, diagnosis of poorly differentiated rectal
      adenocarcinoma was made. The lesion was surgically resected after chemo
      radiotherapy. Histopathological examination of the resected specimen with
      hematoxylin and eosin (HE) stain revealed a single-file arrangement of the tumor
      cells, reminiscent of lobular carcinoma of the breast. Immunohistochemical
      analysis revealed an immunophenotype consistent with lobular carcinoma of the
      breast. Because further review of the patient's history revealed an occurrence of
      'poorly differentiated adenocarcinoma of the breast', which she had experienced
      24 years earlier, the final diagnosis of the lesion was made as rectal metastasis
      from lobular breast carcinoma. CONCLUSIONS: Poorly differentiated adenocarcinoma
      of the colorectum is rarer than that of the stomach. Linitis plastica-type cancer
      of the colorectum is also rarer than that of the stomach. A lesson from the
      present case is that before we conclude a linitis plastica-type cancer of poorly
      differentiated type as a primary colorectal cancer, it is critical to exclude a
      possibility of metastatic colorectal cancer.

PMID- 23114190
TI  - Composite reconstruction of the hip following resection of periacetabular tumors:
      middle-term outcome.
AB  - The records of 18 patients with periacetabular tumors who underwent composite
      reconstruction of the hip following resection of periacetabular tumors were
      analyzed retrospectively. The mean follow-up period was 49.4 months (range, 28
      100 months). During follow-up, 3 patients died and one had recurrence. Fifteen
      patients achieved favorable walking function; 8 had normal hip function and 7 had
      partial recovery of flexion function of the hip. The mean MSTS rating for hip
      function was 76.9%. Two patients had common peroneal nerve injury which was
      resolved in one of them. Middle-term follow-up showed that composite
      reconstruction of the hip following resection of periacetabular tumors can
      effectively remove tumors and provide favorable hip function for these patients.
      This approach is simple and less costly, and can be widely used.

PMID- 23114191
TI  - Revision hip arthroplasty with a modular cementless stem: mid-term follow up.
AB  - Despite the increasing volume of revision total hip arthroplasty (THA) being
      performed in the United States, there are few studies reporting mid-term clinical
      and radiographic outcomes of modular fully porous-coated femoral stems. We
      retrospectively studied a consecutive series of patients who underwent revision
      THA with a modular extensively porous-coated femoral component at a single
      institution and by a single surgeon. The final study group included 54 hips (52
      patients) followed for an average of 84 months. Ten-year survival rates with
      revision for any reason and revision for femoral loosening as endpoints were 94%
      and 100%, respectively. No complications regarding the modular junction were
      encountered. Of the 50 hips with adequate radiographs, all showed proximal
      ingrowth and 42 (84%) had both proximal and distal ingrowth. The modular, fully
      porous-coated femoral stem studied demonstrated excellent survivorship and bone
      ingrowth at mid-term follow up.

PMID- 23114189
TI  - Implications for the mammalian sialidases in the physiopathology of skeletal
      muscle.
AB  - The family of mammalian sialidases is composed of four distinct versatile
      enzymes that remove negatively charged terminal sialic acid residues from
      gangliosides and glycoproteins in different subcellular areas and organelles,
      including lysosomes, cytosol, plasma membrane and mitochondria. In this review we
      summarize the growing body of data describing the important role of sialidases in
      skeletal muscle, a complex apparatus involved in numerous key functions and whose
      functional integrity can be affected by various conditions, such as aging,
      chronic diseases, cancer and neuromuscular disorders. In addition to supporting
      the proper catabolism of glycoconjugates, sialidases can affect different
      signaling pathways by desialylation of many receptors and modulation of
      ganglioside content in cell membranes, thus actively participating in myoblast
      proliferation, differentiation and hypertrophy, insulin responsiveness and
      skeletal muscle architecture.

PMID- 23114192
TI  - Pre-admission cutaneous chlorhexidine preparation reduces surgical site
      infections in total hip arthroplasty.
AB  - The purpose of this study was to evaluate the incidence of surgical site
      infections in total hip arthroplasty patients who used an advance pre-admission
      cutaneous surgical preparation protocol and to compare these results to a cohort
      of patients who did not use the protocol. Between 2007 and 2010, 557 patients
      used the chlorhexidine cloths and 1901 patients did not use the cloths. Patient
      records were reviewed to determine the incidence of deep incisional and
      periprosthetic infections. A statistically significant lower incidence of
      infections occurred in patients who used the chlorhexidine cloths (0.5%) when
      compared to patients undergoing in-hospital perioperative skin preparation only
      (1.7%). These results confirm prior studies suggesting this as an effective
      method to prevent periprosthetic hip arthroplasty infections.

PMID- 23114193
TI  - The use of dermabond(r) as an adjunct to wound closure after total knee
      arthroplasty: examining immediate post-operative wound drainage.
AB  - Wound drainage after total knee arthroplasty (TKA) can be detrimental to surgical
      outcome. This IRB-approved randomized, prospective, blinded study examined the
      use of Dermabond(r) as an adjunct to wound closure after TKA. We proposed that
      Dermabond(r) supplementation to wound closure would result in a significant
      decrease in wound drainage after TKA. After standardized closure, patients were
      randomized into experimental or control groups with the experimental group
      receiving Dermabond(r) supplementation. Standardized dressings were evaluated
      postoperatively and drainage units were compared using a Mann-Whitney U Test. The
      median drainage for the Dermabond group (153) was lower than the drainage for the
      control group (657) at a statistically significant level (P<0.001).

PMID- 23114194
TI  - Reply to the letter to the editor entitled: 'Hsp 27 as a potential preneoplastic
      marker in patients with chronic kidney disease (CKD)'.

PMID- 23114195
TI  - Retrospective epidemiological study for the characterization of community-
      acquired pneumonia and pneumococcal pneumonia in adults in a well-defined area of
      Badalona (Barcelona, Spain).
AB  - BACKGROUND: Community-acquired pneumonia (CAP) has large impact on direct
      healthcare costs, especially those derived from hospitalization. This study
      determines impact, clinical characteristics, outcome and economic consequences of
      CAP in the adult (>=18 years) population attended in 6 primary-care centers and 2
      hospitals in Badalona (Spain) over a two-year period. METHODS: Medical records
      were identified by codes from the International Classification of Diseases in
      databases (January 1st 2008-December 31st 2009). RESULTS: A total of 581 patients
      with CAP (55.6% males, mean age 57.5 years) were identified. Prevalence: 0.64%
      (95% CI: 0.5%-0.7%); annual incidence: 3.0 cases/1,000 inhabitants (95% CI: 0.2
      0.5). Up to 241 (41.5%) required hospitalization. Hospital admission was
      associated (p<0.002) with liver disease (OR=5.9), stroke (OR=3.6), dementia
      (OR=3.5), COPD (OR=2.9), diabetes mellitus (OR=1.9) and age (OR=1.1 per year).
      Length of stay (4.4+/-0.3 days) was associated with PSI score (beta=0.195), in
      turn associated with age (r=0.827) and Charlson index (r=0.497). Microbiological
      tests were performed in all inpatients but only in 35% outpatients. Among
      patients with microbiological tests, results were positive in 51.7%, and among
      them, S pneumoniae was identified in 57.5% cases. Time to recovery was 29.9+/
      17.2 days. Up to 7.5% inpatients presented complications, 0.8% required ICU
      admission and 19.1% readmission. Inhospital mortality rate was 2.5%. Adjusted
      mean total cost was ?2,332.4/inpatient and ?698.6/outpatient (p<0.001). Patients
      with pneumococcal CAP (n=107) showed higher comorbidity and hospitalization
      (76.6%), higher PSI score, larger time to recovery and higher overall costs among
      inpatients. CONCLUSIONS: Strategies preventing CAP, thus reducing hospital
      admissions could likely produce substantial costs savings in addition to the
      reduction of CAP burden.

PMID- 23114197
TI  - Impact on parents of bronchiolitis hospitalization of full-term, preterm and
      congenital heart disease infants.
AB  - BACKGROUND: The objective of this work was to explore the impact on parents of
      the bronchiolitis hospitalization of their infant using the Impact of
      Bronchiolitis Hospitalization Questionnaire (IBHQ(c)). METHODS: Four hundred
      sixty-three infants aged less than 1 year and hospitalized for bronchiolitis were
      included in a French observational study during the 2008-2009 season. Parents
      were asked to complete the IBHQ at hospital discharge and 3 months later. IBHQ
      scores, ranging from 0 (no impact) to 100 (highest impact), were compared
      according to gestational age (full-term, 33-36 wGA, <= 32 wGA) and the presence
      of congenital heart disease (CHD). The potential drivers of impact were explored
      using multivariate linear regressions. RESULTS: The study included 332 full
      terms, 71 infants born at 33-36 wGA, and 60 at <= 32 wGA; 28 infants had a CHD.
      At hospital discharge, 9 of the 12 IBHQ mean scores were above 40, indicating a
      marked impact on parents. Three months later, all mean scores were lower but 5
      were still greater than 40. At discharge, the length of hospitalization had a
      significant effect on IBHQ worries and distress, fear for future, guilt and
      impact on daily organization scores (p<0.01); the parents' educational level had
      a significant effect on IBHQ worries and distress, fear for future, impact on
      daily organization and financial impact scores (p<0.05). The only statistically
      significant difference found between the parents of preterm and full-term infants
      was for the physical impact score at discharge (p=0.004). CONCLUSIONS:
      Bronchiolitis hospitalization has conspicuous emotional, physical and
      organizational consequences on parents and siblings, which persist 3 months after
      hospital discharge. The main drivers of the impact were length of hospital stay
      and parents' educational level, while infants' gestational age or the presence of
      a CHD had little influence.

PMID- 23114198
TI  - The peeling dermatitis with a peculiar demarcation.

PMID- 23114196
TI  - An improved respiratory syncytial virus neutralization assay based on the
      detection of green fluorescent protein expression and automated plaque counting.
AB  - BACKGROUND: Virus neutralizing antibodies against respiratory syncytial virus
      (RSV) are considered important correlates of protection for vaccine evaluation.
      The established plaque reduction assay is time consuming, labor intensive and
      highly variable. METHODS: Here, a neutralization assay based on a modified RSV
      strain expressing the green fluorescent protein in combination with automated
      detection and quantification of plaques is described. RESULTS: The fluorescence
      plaque reduction assay in microplate format requires only two days to complete
      and is simple and reproducible. A good correlation between visual and automated
      counting methods to determine RSV neutralizing serum antibody titers was
      observed. CONCLUSIONS: The developed virus neutralization assay is suitable for
      high-throughput testing and can be used for both animal studies and (large scale)
      vaccine clinical trials.

PMID- 23114199
TI  - The mechanics of left ventricular filling during the strain phase of the valsalva
      maneuver in healthy subjects.
AB  - BACKGROUND: The aim of this study was to investigate the mechanical changes in
      left ventricular filling during the strain phase of the Valsalva maneuver in
      healthy subjects. METHODS: Thirty healthy volunteers were recruited to undertake
      the Valsalva maneuver at a load of 40 mm Hg for 10 seconds. Parameters of left
      ventricle filling were determined by echocardiography at baseline and at the
      first and second beats during the strain phase. RESULTS: Compared with baseline
      values, the E, E/A ratio, E/esep ratio and E/elat ratio parameters all increased
      at the first beat (P < 0.05). Compared with the first beat values, the E, E/A
      ratio, E/esep ratio and E/elat ratio parameters all decreased at the second beat
      (P < 0.05). The results demonstrate that left ventricular filling decreases at
      the second beat during the strain phase of the Valsalva maneuver. Positive
      intrathoracic pressure decreases left-side heart and pulmonary vessel transmural
      pressure while increasing blood vessel resistance, which explains the decrease in
      left ventricular filling. CONCLUSIONS: The results provide a new understanding of
      the underlying mechanical mechanism of the Valsalva maneuver, indicating that it
      should be performed clinically at a lower load and shorter strain time to avoid
      adverse events.

PMID- 23114200
TI  - Oleic acid inhibits the K(ATP) channel subunit Kir6.1 and the K(ATP) current in
      human umbilical artery smooth muscle cells.
AB  - BACKGROUND: The objective of the present study was to determine the effect of
      various concentrations of oleic acid (OA) on KATP channel expression and the
      potential relationship to exogenous nitrogen monoxide and protein kinase C
      levels. METHODS: Human umbilical artery smooth muscle cells (HUASMCs), between
      the 7th and 10th passages, were divided into control group, OA group (final OA
      concentration of 0, 50, 100 or 200 MUmol/L), nitric oxide (NO) intervention
      group, protein kinase C inhibitor group or GF-109203X (GFX) intervention group.
      Western immunoblotting was used to detect the protein expression of the KATP
      channel subunit Kir6.1. Also, quantitative real-time polymerase chain reaction
      analysis to determine Kir6.1 messenger RNA levels and whole-cell patch clamping
      to measure KATP currents were performed. RESULTS: The results suggested that OA
      inhibited Kir6.1 protein and messenger RNA expression in HUASMCs. Under a high
      concentration of potassium (140 mmol/L), 100 MUmol/L OA significantly reduced ATP
      sensitive potassium current density, whereas a low extracellular concentration of
      potassium (5.4 mmol/L) did not influence KATP density. Pretreatment with either
      exogenous NO or GFX weakened the OA-induced inhibition of KATP in HUASMCs.
      CONCLUSIONS: The study demonstrated that OA inhibited Kir6.1, a KATP channel
      subunit, in HUASMCs, and indirectly inhibited the KATP current. In addition, the
      results indicated that NO and/or GFX partially reversed OA inhibition in HUASMCs.

PMID- 23114201
TI  - Negative pressure pulmonary edema.

PMID- 23114202
TI  - Elephantiasis legs.

PMID- 23114203
TI  - Transient dynamics in dense colloidal suspensions under shear: shear rate
      dependence.
AB  - A combination of confocal microscopy and rheology experiments, Brownian dynamics
      (BD) and molecular dynamics (MD) simulations and mode coupling theory (MCT) have
      been applied in order to investigate the effect of shear rate on the transient
      dynamics and stress-strain relations in supercooled and glassy systems under
      shear. Immediately after shear is switched on, the microscopic dynamics display
      super-diffusion and the macroscopic rheology a stress overshoot, which become
      more pronounced with increasing shear rate. MCT relates both to negative sections
      of the generalized shear modulus, which grow with increasing shear rate. When the
      inverse shear rate becomes much smaller than the structural relaxation time of
      the quiescent system, relaxation through Brownian motion becomes less important.
      In this regime, larger stresses are accumulated before the system yields and the
      transition from localization to flow occurs earlier and more abruptly.

PMID- 23114204
TI  - A survey of rodent-borne pathogens carried by wild Rattus spp. in Northern
      Vietnam.
AB  - To examine the prevalence of human pathogens carried by rats in urban areas in
      Hanoi and Hai Phong, Vietnam, we live-trapped 100 rats in January 2011 and
      screened them for a panel of bacteria and viruses. Antibodies against Leptospira
      interrogans (22.0%), Seoul virus (14.0%) and rat hepatitis E virus (23.0%) were
      detected in rats, but antibodies against Yersinia pestis were not detected.
      Antibodies against L. interrogans and Seoul virus were found only in adult rats.
      In contrast, antibodies to rat hepatitis E virus were also found in juvenile and
      sub-adult rats, indicating that the transmission mode of rat hepatitis E virus is
      different from that of L. interrogans and Seoul virus. Moreover, phylogenetic
      analyses of the S and M segments of Seoul viruses found in Rattus norvegicus
      showed that Seoul viruses from Hai Phong and Hanoi formed different clades. Human
      exposure to these pathogens has become a significant public health concern.

PMID- 23114205
TI  - Plasma enterolactone and incidence of endometrial cancer in a case-cohort study
      of Danish women.
AB  - The phyto-oestrogen enterolactone has been hypothesised to protect against
      hormone-dependent cancers, probably through its antioestrogenic potential. We
      investigated whether a higher level of plasma enterolactone was associated with a
      lower incidence of endometrial cancer in a case-cohort study in the 'Diet, Cancer
      and Health' cohort. The cohort study included 29 875 women aged 50-64 years
      enrolled between 1993 and 1997. Information on diet and lifestyle was provided by
      self-administrated questionnaires and blood was drawn from each participant. Time
      resolved fluoroimmunoassay was used for biochemical determination of plasma
      enterolactone. A total of 173 cases and 149 randomly selected cohort members were
      included. We estimated incidence rate ratio (IRR) and 95% CI by a Cox
      proportional hazards model. A 20 nmol/l higher plasma concentration of
      enterolactone was associated with a non-significant lower risk of endometrial
      cancer (IRR 0.93, 95% CI 0.84, 1.04). When excluding women with low enterolactone
      concentrations (quartile 1) due to potential recent antibiotic use, the
      association became slightly stronger, but remained non-significant (IRR 0.90, 95%
      CI 0.79, 1.02). Menopausal status, hormone replacement therapy or BMI did not
      modify the association. In conclusion, we found some support for a possible
      inverse association between plasma enterolactone concentration and endometrial
      cancer incidence.

PMID- 23114206
TI  - Independent transmission of convergent visceral primary afferents in the solitary
      tract nucleus.
AB  - Cranial primary afferents from the viscera enter the brain at the solitary tract
      nucleus (NTS), where their information is integrated for homeostatic reflexes.
      The organization of sensory inputs is poorly understood, despite its critical
      impact on overall reflex performance characteristics. Single afferents from the
      solitary tract (ST) branch within NTS and make multiple contacts onto individual
      neurons. Many neurons receive more than one ST input. To assess the potential
      interaction between converging afferents and proximal branching near to second
      order neurons, we probed near the recorded soma in horizontal slices from rats
      with focal electrodes and minimal shocks. Remote ST shocks evoked monosynaptic
      excitatory postsynaptic currents (EPSCs), and nearby focal shocks also activated
      monosynaptic EPSCs. We tested the timing and order of stimulation to determine
      whether focal shocks influenced ST responses and vice versa in single neurons.
      Focal-evoked EPSC response profiles closely resembled ST-EPSC characteristics.
      Mean synaptic jitters, failure rates, depression, and phenotypic segregation by
      capsaicin responsiveness were indistinguishable between focal and ST-evoked
      EPSCs. ST-EPSCs failed to affect focal-EPSCs within neurons, indicating that
      release sites and synaptic terminals were functionally independent and isolated
      from cross talk or neurotransmitter overflow. In only one instance, focal shocks
      intercepted and depleted the ST axon generating evoked EPSCs. Despite large
      numbers of functional contacts, multiple afferents do not appear to interact, and
      ST axon branches may be limited to close to the soma. Thus single or multiple
      primary afferents and their presynaptic active release sites act independently
      when they contact single second-order NTS neurons.

PMID- 23114207
TI  - Recording EEG in immature rats with a novel miniature telemetry system.
AB  - Serial EEG recordings from immature rat pups are extremely difficult to obtain
      but important for analyzing animal models of neonatal seizures and other
      pediatric neurological conditions as well as normal physiology. In this report,
      we describe the features and applications of a novel miniature telemetry system
      designed to record EEG in rat pups as young as postnatal day 6 (P6). First, we
      have recorded electrographic seizure activity in two animal models of neonatal
      seizures, hypoxia- and kainate-induced seizures at P7. Second, we describe a
      viable approach for long-term continuous EEG monitoring of naturally reared rat
      pups implanted with EEG at P6. Third, we have used serial EEG recordings to
      record age-dependent changes in the background EEG signal as the animals matured
      from P7 to P11. The important advantages of using miniature wireless EEG
      technology are: 1) minimally invasive surgical implantation; 2) a device form
      factor that is compatible with housing of rat pups with the dam and littermates;
      3) serial recordings of EEG activity; and 4) low power consumption of the unit,
      theoretically allowing continuous monitoring for up to 2 yr without surgical
      reimplantation. The miniature EEG telemetry system provides a technical advance
      that allows researchers to record continuous and serial EEG recordings in
      neonatal rodent models of human neurological disorders, study the progression of
      the disease, and then assess possible therapies using quantitative EEG as an
      outcome measure. This new technical approach should improve animal models of
      human conditions that rely on EEG monitoring for diagnosis and therapy.

PMID- 23114208
TI  - Firing rate and pattern heterogeneity in the globus pallidus arise from a single
      neuronal population.
AB  - Intrinsic heterogeneity in networks of interconnected cells has profound effects
      on synchrony and spike-time reliability of network responses. Projection neurons
      of the globus pallidus (GPe) are interconnected by GABAergic inhibitory synapses
      and in vivo fire continuously but display significant rate and firing pattern
      heterogeneity. Despite being deprived of most of their synaptic inputs, GPe
      neurons in slices also fire continuously and vary greatly in their firing rate (1
      70 spikes/s) and in regularity of their firing. We asked if this rate and pattern
      heterogeneity arises from separate cell types differing in rate, local synaptic
      interconnections, or variability of intrinsic properties. We recorded the resting
      discharge of GPe neurons using extracellular methods both in vivo and in vitro.
      Spike-to-spike variability (jitter) was measured as the standard deviation of
      interspike intervals. Firing rate and jitter covaried continuously, with slow
      firing being associated with higher variability than faster firing, as would be
      expected from heterogeneity arising from a single physiologically distinct cell
      type. The relationship between rate and jitter was unaffected by blockade of GABA
      and glutamate receptors. When the firing rate of individual neurons was altered
      with constant current, jitter changed to maintain the rate-jitter relationship
      seen across neurons. Long duration (30-60 min) recordings showed slow and
      spontaneous bidirectional drift in rate similar to the across-cell heterogeneity.
      Paired recordings in vivo and in vitro showed that individual cells wandered in
      rate independently of each other. Input conductance and rate wandered together,
      in a manner suggestive that both were due to fluctuations of an inward current.

PMID- 23114209
TI  - Computing reaching dynamics in motor cortex with Cartesian spatial coordinates.
AB  - How neurons in the primary motor cortex control arm movements is not yet
      understood. Here we show that the equations of motion governing reaching simplify
      when expressed in spatial coordinates. In this fixed reference frame, joint
      torques are the sums of vector cross products between the spatial positions of
      limb segments and their spatial accelerations and velocities. The consequences
      that follow from this model explain many properties of neurons in the motor
      cortex, including directional broad, cosinelike tuning, nonuniformly distributed
      preferred directions dependent on the workspace, and the rotation of the
      population vector during arm movements. Remarkably, the torques can be directly
      computed as a linearly weighted sum of responses from cortical motoneurons, and
      the muscle tensions can be obtained as rectified linear sums of the joint
      torques. This allows the required muscle tensions to be computed rapidly from a
      trajectory in space with a feedforward network model.

PMID- 23114210
TI  - Rapid regulation of tonic GABA currents in cultured rat hippocampal neurons.
AB  - Subacute and chronic changes in tonic GABAergic inhibition occur in human and
      experimental epilepsy. Less is known about how tonic inhibition is modulated over
      shorter time frames (seconds). We measured endogenous tonic GABA currents from
      cultured rat hippocampal neurons to evaluate how they are affected by 1)
      transient increases in extracellular GABA concentration ([GABA]), 2) transient
      postsynaptic depolarization, and 3) depolarization of presynaptic cells.
      Transient increases in [GABA] (1 MUM) reduced tonic currents; this reduction
      resulted from GABA-induced shifts in the reversal potential for GABA currents
      (E(GABA)). Transient depolarization of postsynaptic neurons reversed the effects
      of exogenous GABA and potentiated tonic currents. The voltage-dependent
      potentiation of tonic GABA currents was independent of E(GABA) shifts and
      represented postdepolarization potentiation (PDP), an intrinsic GABA(A) receptor
      property (Ransom CB, Wu Y, Richerson GB. J Neurosci 30: 7672-7684, 2010).
      Inhibition of vesicular GABA release with concanamycin A (ConA) did not affect
      tonic currents. In ConA-treated cells, transient application of 12 mM K(+) to
      depolarize presynaptic neurons and glia produced a persistent increase in tonic
      current amplitude. The K(+)-induced increase in tonic current was reversibly
      inhibited by SKF89976a (40 MUM), indicating that this was caused by nonvesicular
      GABA release from GABA transporter type 1 (GAT1). Nonvesicular GABA release due
      to GAT1 reversal also occurred in acute hippocampal brain slices. Our results
      indicate that tonic GABA currents are rapidly regulated by GABA-induced changes
      in intracellular Cl(-) concentration, PDP of extrasynaptic GABA(A) receptors, and
      nonvesicular GABA release. These mechanisms may influence tonic inhibition during
      seizures when neurons are robustly depolarized and extracellular GABA and K(+)
      concentrations are elevated.

PMID- 23114211
TI  - Postural adjustment errors reveal deficits in inhibition during lateral step
      initiation in older adults.
AB  - Postural dual-task studies have demonstrated effects of various executive
      function components on gait and postural control in older adults. The purpose of
      the study was to explore the role of inhibition during lateral step initiation.
      Forty older adults participated (range 70-94 yr). Subjects stepped to the left or
      right in response to congruous and incongruous visual cues that consisted of left
      and right arrows appearing on left or right sides of a monitor. The timing of
      postural adjustments was identified by inflection points in the vertical ground
      reaction forces (VGRF) measured separately under each foot. Step responses could
      be classified into preferred and nonpreferred step behavior based on the number
      of postural adjustments that were made. Delays in onset of the first postural
      adjustment (PA1) and liftoff (LO) of the step leg during preferred steps
      progressively increased among the simple, choice, congruous, and incongruous
      tasks, indicating interference in processing the relevant visuospatial cue.
      Incongruous cues induced subjects to make more postural adjustments than they
      typically would (i.e., nonpreferred steps), representing errors in selection of
      the appropriate motor program. During these nonpreferred steps, the onset of the
      PA1 was earlier than during the preferred steps, indicating a failure to inhibit
      an inappropriate initial postural adjustment. The functional consequence of the
      additional postural adjustments was a delay in the LO compared with steps in
      which they did not make an error. These results suggest that deficits in
      inhibitory function may detrimentally affect step decision processing, by
      delaying voluntary step responses.

PMID- 23114213
TI  - Biophysical determinants of transcranial magnetic stimulation: effects of
      excitability and depth of targeted area.
AB  - Safe and effective transcranial magnetic stimulation (TMS) requires accurate
      intensity calibration. Output is typically calibrated to individual motor cortex
      excitability and applied to nonmotor brain areas, assuming that it captures a
      site nonspecific factor of excitability. We tested this assumption by correlating
      the effect of TMS at motor and visual cortex. In 30 participants, we measured
      motor threshold (MT) and phosphene threshold (PT) at the scalp surface and at
      coil-scalp distances of 3.17, 5.63, and 9.03 mm. We also modeled the effect of
      TMS in a simple head model to test the effect of distance. Four independent tests
      confirmed a significant correlation between PT and MT. We also found similar
      effects of distance in motor and visual areas, which did not correlate across
      participants. Computational modeling suggests that the relationship between the
      effect of distance and the induced electric field is effectively linear within
      the range of distances that have been explored empirically. We conclude that MT
      guided calibration is valid for nonmotor brain areas if coil-cortex distance is
      taken into account. For standard figure-of-eight TMS coils connected to biphasic
      stimulators, the effect of cortical distance should be adjusted using a general
      correction factor of 2.7% stimulator output per millimeter.

PMID- 23114214
TI  - Ketamine disrupts theta synchrony across the septotemporal axis of the CA1 region
      of hippocampus.
AB  - The hippocampal theta signal reflects moment-to-moment variation in the synchrony
      of synaptic input to hippocampal neurons. Consistent with the topography of
      hippocampal afferents, the synchrony (coherence) of the theta signal varies
      across the septotemporal axis. Septotemporal variation in the theta signal can
      also be observed in relation to ongoing and past experience. Thus there is a
      systematic decrease in the relationship between locomotor speed and theta power
      across the septotemporal axis, septal hippocampus exhibiting the strongest
      relationship. Conversely, theta in temporal hippocampus decrements over repeated
      behavioral experience (running episodes), while theta in the septal hippocampus
      does not. Ketamine is an N-methyl-D-aspartate (NMDA) antagonist that can decrease
      theta power. The present study examined whether ketamine treatment could alter
      theta coherence across the long axis independent of changes in locomotor
      behavior. Rats were well trained to navigate a linear runway and outfitted with
      electrodes at different septotemporal positions within CA1. Locomotor behavior
      and theta coherence and power were examined after administration of 2.5 and 10
      mg/kg ketamine. Ketamine (2.5 mg/kg) decreased theta coherence between distant
      CA1 electrode sites without altering running speed or theta power. Both doses of
      ketamine also blunted and reversed the decrement in theta power observed at
      midseptotemporal and temporal electrodes over repeated run sessions. The results
      demonstrate the sensitivity of global network synchronization to relatively low
      doses of ketamine and septotemporal differences in the influence of ketamine on
      hippocampal dynamics in relation to past experience.

PMID- 23114212
TI  - Multisensory plasticity in adulthood: cross-modal experience enhances neuronal
      excitability and exposes silent inputs.
AB  - Multisensory superior colliculus neurons in cats were found to retain substantial
      plasticity to short-term, site-specific experience with cross-modal stimuli well
      into adulthood. Following cross-modal exposure trials, these neurons
      substantially increased their sensitivity to the cross-modal stimulus
      configuration as well as to its individual component stimuli. In many cases, the
      exposure experience also revealed a previously ineffective or "silent" input
      channel, rendering it overtly responsive. These experience-induced changes
      required relatively few exposure trials and could be retained for more than 1 h.
      However, their induction was generally restricted to experience with cross-modal
      stimuli. Only rarely were they induced by exposure to a modality-specific
      stimulus and were never induced by stimulating a previously ineffective input
      channel. This short-term plasticity likely provides substantial benefits to the
      organism in dealing with ongoing and sequential events that take place at a given
      location in space and may reflect the ability of multisensory superior colliculus
      neurons to rapidly alter their response properties to accommodate to changes in
      environmental challenges and event probabilities.

PMID- 23114215
TI  - Short-term synaptic depression and stochastic vesicle dynamics reduce and shape
      neuronal correlations.
AB  - Correlated neuronal activity is an important feature in many neural codes, a
      neural correlate of a variety of cognitive states, as well as a signature of
      several disease states in the nervous system. The cellular and circuit mechanics
      of neural correlations is a vibrant area of research. Synapses throughout the
      cortex exhibit a form of short-term depression where increased presynaptic firing
      rates deplete neurotransmitter vesicles, which transiently reduces synaptic
      efficacy. The release and recovery of these vesicles are inherently stochastic,
      and this stochasticity introduces variability into the conductance elicited by
      depressing synapses. The impact of spiking and subthreshold membrane dynamics on
      the transfer of neuronal correlations has been studied intensively, but an
      investigation of the impact of short-term synaptic depression and stochastic
      vesicle dynamics on correlation transfer is lacking. We find that short-term
      synaptic depression and stochastic vesicle dynamics can substantially reduce
      correlations, shape the timescale over which these correlations occur, and alter
      the dependence of spiking correlations on firing rate. Our results show that
      short-term depression and stochastic vesicle dynamics need to be taken into
      account when modeling correlations in neuronal populations.

PMID- 23114216
TI  - Updating of the spatial reference frame of head direction cells in response to
      locomotion in the vertical plane.
AB  - Many species navigate in three dimensions and are required to maintain accurate
      orientation while moving in an Earth vertical plane. Here we explored how head
      direction (HD) cells in the rat anterodorsal thalamus responded when rats
      locomoted along a 360 degrees  spiral track that was positioned vertically within
      the room at the N, S, E, or W location. Animals were introduced into the vertical
      plane either through passive placement (experiment 1) or by allowing them to run
      up a 45 degrees  ramp from the floor to the vertically positioned platform
      (experiment 2). In both experiments HD cells maintained direction-specific firing
      in the vertical plane with firing properties that were indistinguishable from
      those recorded in the horizontal plane. Interestingly, however, the cells'
      preferred directions were linked to different aspects of the animal's environment
      and depended on how the animal transitioned into the vertical plane. When animals
      were passively placed onto the vertical surface, the cells switched from using
      the room (global cues) as a reference frame to using the vertically positioned
      platform (local cues) as a reference frame, independent of where the platform was
      located. In contrast, when animals self-locomoted into the vertical plane, the
      cells' preferred directions remained anchored to the three-dimensional room
      coordinates and their activity could be accounted for by a simple 90 degrees 
      rotation of the floor's horizontal coordinate system to the vertical plane. These
      findings highlight the important role that active movement signals play for
      maintaining and updating spatial orientation when moving in three dimensions.

PMID- 23114217
TI  - Populations of striatal medium spiny neurons encode vibrotactile frequency in
      rats: modulation by slow wave oscillations.
AB  - Dorsolateral striatum (DLS) is implicated in tactile perception and receives
      strong projections from somatosensory cortex. However, the sensory
      representations encoded by striatal projection neurons are not well understood.
      Here we characterized the contribution of DLS to the encoding of vibrotactile
      information in rats by assessing striatal responses to precise frequency stimuli
      delivered to a single vibrissa. We applied stimuli in a frequency range (45-90
      Hz) that evokes discriminable percepts and carries most of the power of vibrissa
      vibration elicited by a range of complex fine textures. Both medium spiny neurons
      and evoked potentials showed tactile responses that were modulated by slow wave
      oscillations. Furthermore, medium spiny neuron population responses represented
      stimulus frequency on par with previously reported behavioral benchmarks. Our
      results suggest that striatum encodes frequency information of vibrotactile
      stimuli which is dynamically modulated by ongoing brain state.

PMID- 23114218
TI  - The response of Na(V)1.3 sodium channels to ramp stimuli: multiple components and
      mechanisms.
AB  - Na(V)1.3 voltage-gated sodium channels have been shown to be expressed at
      increased levels within axotomized dorsal root ganglion neurons and within
      injured axons within neuromas and have been implicated in neuropathic pain. Like
      a number of other sodium channel isoforms, Na(V)1.3 channels produce a robust
      response to slow ramplike stimuli. Here we show that the response of Na(V)1.3 to
      ramp stimuli consists of two components: an early component, dependent upon ramp
      rate, that corresponds to a window current that is dependent upon closed-state
      inactivation; and a second component at more depolarized potentials that is
      correlated with persistent current which is detected for many tens of
      milliseconds after the start of a depolarizing pulse. We also assessed the K354Q
      Na(V)1.3 epilepsy-associated mutant channel, which is known to display an
      enhanced persistent current and demonstrate a strong correlation with the second
      component of the ramp response. Our results show that a single sodium channel
      isoform can produce a ramp response with multiple components, reflecting multiple
      mechanisms, and suggest that the upregulated expression of Na(V)1.3 in axotomized
      dorsal root ganglion neurons and enhanced ramp current in K354Q mutant channels
      can contribute in several ways to hyperexcitability and abnormal spontaneous
      firing that contribute to hyperexcitability disorders, such as epilepsy and
      neuropathic pain.

PMID- 23114220
TI  - Controlling the wetting properties of the Asakura-Oosawa model and applications
      to spherical confinement.
AB  - We demonstrate for the Asakura-Oosawa model and an extension of this model that
      uses continuous rather than hard potentials, how wetting properties at walls can
      be easily controlled. By increasing the interaction range of the repulsive wall
      potential acting on the colloids (while keeping the polymer-wall interactions
      constant) polymers begin to substitute colloids at walls and the system can be
      driven from complete wetting of colloids via partial wetting to complete wetting
      of polymers. As an application, we discuss the morphology and wetting behavior of
      colloid-polymer mixtures in spherical confinement. We apply the recently
      developed 'ensemble switch method' where the Hamiltonian is extended to a
      combination of a system with walls and of a system without walls to calculate the
      surface excess free energies of colloid-rich and polymer-rich phases. The contact
      angle then is inferred from Young's equation.

PMID- 23114219
TI  - Neurotrophins regulate cholinergic synaptic transmission in cultured rat
      sympathetic neurons through a p75-dependent mechanism.
AB  - The sympathetic nervous system regulates many essential physiological systems,
      and its dysfunction is implicated in cardiovascular diseases. Mechanisms that
      control the strength of sympathetic output are therefore potential targets for
      the management of these disorders. Here we show that neurotrophins rapidly
      potentiate cholinergic transmission between cultured rat sympathetic neurons. We
      found that brain-derived neurotrophic factor (BDNF) and nerve growth factor
      (NGF), acting at the p75 receptor, increased the amplitude of excitatory
      postsynaptic currents (EPSCs). We observed increased amplitude but not frequency
      of miniature synaptic currents after p75 activation, suggesting that p75 acts
      postsynaptically to modulate transmission at these synapses. This neurotrophic
      modulation enhances cholinergic EPSCs via sphingolipid signaling. Application of
      sphingolactone-24, an inhibitor of neutral sphingomyelinase, blocked the effect
      of BDNF, implicating a sphingolipid pathway. Furthermore, application of the p75
      associated sphingolipid second messengers C(2)-ceramide and d-erythro-sphingosine
      restricted to the postsynaptic cell mimicked BDNF application. Postsynaptic
      blockade of ceramide production with fumonisin, a ceramide synthase inhibitor,
      blocked the effects of BDNF and d-erythro-sphingosine, implicating ceramide or
      ceramide phosphate as the active signal. Together these data suggest that
      neurotrophin signaling, which occurs in vivo via release from sympathetic neurons
      and target tissues such as the heart, acutely regulates the strength of the
      sympathetic postganglionic response to central cholinergic inputs. This pathway
      provides a potential mechanism for modulating the strength of sympathetic drive
      to target organs such as the heart and could play a role in the development of
      cardiovascular diseases.

PMID- 23114221
TI  - Dynamics of individual colloidal particles in one-dimensional random potentials:
      a simulation study.
AB  - Using Monte Carlo simulations, individual Brownian particles have been
      investigated in a one-dimensional random energy landscape whose energy levels are
      selected from a Gaussian distribution. The standard deviation of the distribution
      determines the roughness of the noise-like potential and was varied in the
      simulations. After initialization, which was done by an instantaneous or
      infinitely slow (annealed)  quench, the particle dynamics were followed. They
      were characterized by a number of parameters, such as the mean squared
      displacement, the time dependent diffusion coefficient, the non-Gaussian
      parameter, and the van Hove function. The dynamics exhibit different regimes: at
      very short times superdiffusion, followed by normal diffusion, and subsequently
      an extended period of subdiffusive dynamics due to localization within the minima
      of the potential, and finally, after a very slow approach towards the long-time
      limit, again diffusion with a significantly reduced diffusion coefficient. The
      long-time diffusion coefficient is consistent with theoretical predictions while
      no predictions exist for the intermediate times. Nevertheless, over the whole
      time range, the simulation results are in agreement with recent experimental
      findings on colloidal particles in a random potential created by a holographic
      optical setup.

PMID- 23114222
TI  - An assessment of the likely acceptability of vaginal microbicides for HIV
      prevention among women in rural Ghana.
AB  - BACKGROUND: The findings of the CAPRISA tenofovir studies have raised
      expectations that soon an approved microbicide would be available. However it is
      in only a limited number of countries in sub-Saharan Africa that the
      acceptability of microbicides has been evaluated. We conducted a study to assess
      the acceptability of vaginal microbicides among women in rural Ghana. METHODS:
      The study employs a mixed method design, using cross-sectional survey and focus
      group discussions to further understand issues related to awareness and attitudes
      towards microbicide development, acceptability and perceived partner attitudes
      among pregnant women attending antenatal clinic in two health facilities in the
      Kintampo North municipality of Ghana. We used logistic regression to identify
      possible predictors of microbicide acceptability among the women surveyed.
      RESULTS: Although only 2% of the 504 women were aware of the development of
      microbicides, 95% were willing to use one when it became available. The cost of a
      microbicide that will be considered affordable to 50% of women was US$0.75.
      Although there were concerns about possible wetting effect, gel or creams were
      the most preferred (68% of women) formulation. Although 71% thought their
      partners will find microbicide acceptable, apprehensions about the feasibility of
      and consequences of failed discreet use were evident. 49% of women were concerned
      about possible negative effect of microbicide on sexual pleasure. Perceived
      partner acceptability (O.R. =17.7; 95%C.I. 5.03-62.5) and possibility of discreet
      use (O.R. =8.9 95%C.I. 2.63-30.13) were the important predictors of microbicide
      acceptability. CONCLUSION: Achieving microbicide acceptability among male
      partners should be made a part of the promotive interventions for ensuring
      effective use among women in rural Ghana.

PMID- 23114223
TI  - Joint X-ray crystallographic and molecular dynamics study of cellobiohydrolase I
      from Trichoderma harzianum: deciphering the structural features of
      cellobiohydrolase catalytic activity.
AB  - Aiming to contribute toward the characterization of new, biotechnologically
      relevant cellulolytic enzymes, we report here the first crystal structure of the
      catalytic core domain of Cel7A (cellobiohydrolase I) from the filamentous fungus
      Trichoderma harzianum IOC 3844. Our structural studies and molecular dynamics
      simulations show that the flexibility of Tyr260, in comparison with Tyr247 from
      the homologous Trichoderma reesei Cel7A, is enhanced as a result of the short
      side-chains of adjacent Val216 and Ala384 residues and creates an additional gap
      at the side face of the catalytic tunnel. T. harzianum cellobiohydrolase I also
      has a shortened loop at the entrance of the cellulose-binding tunnel, which has
      been described to interact with the substrate in T. reesei Cel7A. These
      structural features might explain why T. harzianum Cel7A displays higher k(cat)
      and K(m) values, and lower product inhibition on both glucoside and lactoside
      substrates, compared with T. reesei Cel7A.

PMID- 23114224
TI  - Efficacy and safety of a TIA/stroke electronic support tool (FASTEST) trial:
      study protocol.
AB  - BACKGROUND: Strokes are a common cause of adult disability and mortality
      worldwide. Transient ischaemic attacks (TIA) are associated with a high risk of
      subsequent stroke, and rapid intervention has the potential to reduce stroke
      burden. This study will assess a novel electronic decision support (EDS) tool to
      allow general practitioners (GPs) to implement evidence-based care rapidly
      without full reliance on specialists. METHODS/DESIGN: This is a cluster
      randomized controlled trial comparing TIA/stroke management of GPs with access to
      the EDS tool versus usual care. The intervention period is 12 months with a 3
      month follow-up period for individual patients. Primary outcomes consist of
      stroke within 90 days of presenting event and adherence to the New Zealand
      national TIA guideline. DISCUSSION: A positive study will provide strong evidence
      for widespread implementation of this tool in practice and has the potential to
      improve key outcomes for patients and reduce the burden of stroke. TRIAL
      REGISTRATION: Australia New Zealand Clinical Trials Registry ACTRN12611000792921.

PMID- 23114225
TI  - Crystalline multilayers of charged colloids in soft confinement: experiment
      versus theory.
AB  - We combine real-space experiments and lattice sum calculations to investigate the
      phase diagram of charged colloidal particles under soft confinement. In the
      experiments we explore the equilibrium phase diagram of charged colloidal spheres
      in aqueous suspensions confined between two parallel charged walls at low
      background salt concentrations. Motivated by the experiments, we perform lattice
      sum minimizations to predict the crystalline ground state of point-like Yukawa
      particles which are exposed to a soft confining wall potential. In the
      multilayered crystalline regime, we obtain good agreement between the
      experimental and numerical findings: upon increasing the density we recover the
      sequence [structure: see text].

PMID- 23114226
TI  - Spontaneous genetic clustering in populations of competing organisms.
AB  - We introduce and analyse an individual-based evolutionary model, in which a
      population of genetically diverse organisms compete with each other for limited
      resources. Through theoretical analysis and stochastic simulations, we show that
      the model exhibits a pattern-forming instability which is highly amplified by the
      effects of demographic noise, leading to the spontaneous formation of genotypic
      clusters. This mechanism supports the thesis that stochasticity has a central
      role in the formation and coherence of species.

PMID- 23114227
TI  - Multiple congenital comedones, hearing impairment and intellectual disability: a
      new syndromic association?

PMID- 23114228
TI  - A systematic review of the use of financial incentives and penalties to encourage
      uptake of healthy behaviors: protocol.
AB  - BACKGROUND: The use of financial incentives and penalties to encourage uptake of
      healthy behaviors is increasingly seen as a viable intervention in developed
      countries. Previous reviews of the effectiveness of financial incentives and
      penalties for encouraging the uptake of healthy behaviors have focused on
      individual behaviors making it difficult to draw overall conclusions about the
      effectiveness of such interventions. This systematic review will explore the
      effectiveness of financial incentives and penalties for encouraging a wide range
      of behaviors, including: smoking cessation, increased physical activity,
      healthier dietary intake, sensible patterns of alcohol consumption, safe sun,
      safe sex, and primary preventive clinical behaviors. METHODS: Systematic methods
      will be used to search existing literature and screen studies for inclusion. All
      studies that meet the following inclusion criteria will be included in the
      review: participants were 18 years old or older and living in high-income
      countries; interventions included cash or cash-like incentives to promote the
      uptake of healthy behaviors, or cash or cash-like penalties to discourage
      unhealthy behaviors; the comparator was usual care or no intervention; study
      design was randomized controlled trial, cluster randomized controlled trial,
      controlled before and after study, or interrupted time series analysis. Two
      reviewers will independently screen the publications to ensure they meet the
      inclusion criteria. Quality will be assessed by two researchers, working
      independently, using the Cochrane risk of bias tool. Meta-analysis will be
      conducted, if appropriate. Any studies identified as at 'high risk of bias' will
      be excluded from meta-analysis. DISCUSSION: This systematic review will provide
      policy-relevant recommendations for the use of financial incentives and penalties
      as a method of encouraging uptake of healthy behaviors.

PMID- 23114229
TI  - Force-induced diffusion in microrheology.
AB  - We investigate the force-induced diffusive motion of a tracer particle inside a
      glass-forming suspension when a strong external force is applied to the probe
      (active nonlinear microrheology). A schematic model of mode-coupling theory
      introduced recently is extended to describe the transient dynamics of the probe
      particle, and used to analyze recent molecular-dynamics simulation data. The
      model describes non-trivial transient displacements of the probe before a steady
      state velocity is reached. The external force also induces diffusive motion in
      the direction perpendicular to its axis. We address the relation between the
      transverse diffusion coefficient D(perpendicular) and the force-dependent
      nonlinear friction coefficient zeta. Non-diffusive fluctuations in the direction
      of the force are seen at long times in the MD simulation, while the model
      describes cross-over to long-time diffusion.

PMID- 23114230
TI  - Primary pulmonary mucoepidermoid carcinoma: an analysis of 21 cases.
AB  - BACKGROUND: The optimal treatment for pulmonary mucoepidermoid carcinoma (MEC), a
      rare type of tumor, has not been established yet. This study analyzed the
      survival of pulmonary MEC patients and attempted to find clues for optimal
      treatment. METHODS: A total of 21 patients with pulmonary MEC from November 2004
      to January 2011 were included in the investigation. Immunohistochemistry,
      epidermal growth factor receptor (EGFR) mutation, and survival were
      retrospectively studied. RESULTS: Among the 21 pulmonary MEC patients, 17 were
      diagnosed with low-grade malignancy and 4 with high-grade malignancy through
      pathological examination. The prognosis was found to be poor in the presence of
      lymph nodes. The expression rates of EGFR and HER2 were 28.6% and 0%,
      respectively, which correlated with neither grade nor prognosis. The mutation
      rate of EGFR was 0. Log-rank test results indicated that age, grade, lymph node
      metastasis, and tumor-node-metastasis stage were prognostic factors. CONCLUSION:
      Age, grade, lymph node metastasis and tumor-node-metastasis stage correlate with
      the survival of pulmonary MEC patients. TRIAL REGISTRATION: This study was
      approved and registered by the Ethics Committee of Zhongshan Hospital. Written
      informed consent was obtained from all participants prior to treatment.

PMID- 23114231
TI  - Use of high-flow nasal cannula support in the emergency department reduces the
      need for intubation in pediatric acute respiratory insufficiency.
AB  - OBJECTIVES: The objective of this study was to determine whether the use of
      heated, humidified, high-flow nasal cannula (HFNC) therapy is associated with a
      decreased need for intubation in patients presenting to a pediatric emergency
      department (PED) and admitted to a pediatric intensive care unit (PICU) with
      acute respiratory insufficiency (ARI). METHODS: A retrospective study of all
      patients admitted from the PED to the PICU with ARI from January 2006 through
      December 2009. Patients admitted before the availability of HFNC (cohort 1) were
      compared with those admitted after the availability of HFNC but before
      implementation of an institution-wide guideline on pediatric HFNC usage (cohort
      2) and those admitted after the implementation of a pediatric HFNC usage
      guideline (cohort 3). RESULTS: After controlling for age, month of admission,
      type of respiratory illness, and severity of illness, there was an 83% reduction
      in the odds of intubation in the PED in cohort 3 compared with cohort 1 (odds
      ratio, 0.17; 95% confidence interval, 0.06-0.50; P = 0.001). There was no
      significant change in mortality or median PICU length of stay after the
      introduction of HFNC. CONCLUSIONS: High-flow nasal cannula used early in the
      development of pediatric ARI is associated with a decreased the need for
      intubation and mechanical ventilation.

PMID- 23114232
TI  - Developing measures of quality for the emergency department management of
      pediatric suicide-related behaviors.
AB  - OBJECTIVE: Given the public health importance of suicide-related behaviors and
      the corresponding gap in the performance measurement literature, we sought to
      identify key candidate process indicators (quality of care measures) and
      structural measures (organizational resources and attributes) important for
      emergency department (ED) management of pediatric suicide-related behaviors.
      METHODS: We reviewed nationally endorsed guidelines and published research to
      establish an inventory of measures. Next, we surveyed expert pediatric ED
      clinicians to assess the level of agreement on the relevance (to patient care)
      and variability (across hospitals) of 42 candidate process indicators and whether
      10 hospital and regional structural measures might impact these processes.
      RESULTS: Twenty-three clinicians from 14 pediatric tertiary-care hospitals
      responded (93% of hospitals contacted). Candidate process indicators identified
      as both most relevant to patient care (>=87% agreed or strongly agreed) and most
      variable across hospitals (>=78% agreed or strongly agreed) were wait time for
      medical assessment; referral to crisis intervention worker/program; mental
      health, psychosocial, or risk assessment requested; any inpatient admission;
      psychiatric inpatient admission; postdischarge treatment plan; wait time for
      first follow-up appointment; follow-up obtained; and type of follow-up obtained.
      Key hospital and regional structural measures (>=87% agreed or strongly agreed)
      were specialist staffing and type of specialist staffing in or available to the
      ED; regional policies, protocols, or procedures; and inpatient psychiatric
      services. CONCLUSIONS: This study highlighted candidate performance measures for
      the ED management of pediatric suicide-related behaviors. The 9 candidate process
      indicators (covering triage, assessment, admission, discharge, and follow-up) and
      4 hospital and regional structural measures merit further development.

PMID- 23114233
TI  - Risk factors for admission in children with bronchiolitis from pediatric
      emergency department observation unit.
AB  - BACKGROUND: Patients with bronchiolitis are increasingly being admitted to
      emergency department observation units (EDOUs) but often require subsequent
      hospitalization. To better identify ED patients who should be directly admitted
      to the hospital rather than the EDOU, the predictors of admission must be
      identified. OBJECTIVES: The objective of this study was to determine the
      predictors of subsequent hospital admission from the EDOU in infants and young
      children with bronchiolitis. METHOD: This was a retrospective cohort study of
      patients younger than 2 years admitted to an EDOU with bronchiolitis between
      April 1, 2003, and March 31, 2007. Univariate analysis was followed by logistic
      regression to identify the significant predictors of hospital admission from the
      EDOU. RESULTS: There were 325 patients in the study: 67% were younger than 6
      months, and 60% were male. Eighty-five (26%) were admitted to the hospital from
      the EDOU. Predictors for admission from the EDOU included parental report of poor
      feeding or increased work of breathing, oxygen saturation less than 93%, or ED
      treatment with racemic epinephrine (Vaponephrine) and intravenous fluids (IVFs).
      CONCLUSION: Patients with a history of increased work of breathing or oxygen
      saturation less than 93% and ED treatment with IVFs are at high risk for
      admission from the EDOU to the hospital. Direct admission to the hospital from
      the ED should be considered for these patients, particularly patients treated
      with IVFs and having an oxygen saturation less than 93% in the ED.

PMID- 23114234
TI  - Pediatric endotracheal intubations for airway management in the emergency
      department.
AB  - OBJECTIVE: The objective of this study was to determine indications, type of
      medications used, and immediate complications of pediatric endotracheal
      intubations in the emergency department. METHODS: A retrospective chart review
      was done on all pediatric patients (0-14 years old) who required endotracheal
      (ET) intubation for airway management in the Department of Emergency Medicine at
      Aga Khan University Hospital from January to December 2009. Data were collected
      on a preformed questionnaire for age, sex, indications, drugs used, and
      complications of pediatric ET intubations done in the emergency department. Dead
      on-arrival patients and those intubated elsewhere were excluded. RESULTS: A total
      of 83 pediatric intubations were done during the study period. Indications for ET
      intubations were respiratory failure in 51 (61%), unresponsiveness in 18 (22%),
      cardiac arrest in 8 (10%), and trauma in 6 cases (7%). Comorbid conditions were
      present in 28 (34%). Of 83 ET intubations, drugs were used in 48 cases (58%).
      Both sedation and neuromuscular blockade were used in 42 cases (51%), 4 cases
      (5%) received sedation only, and 2 cases (2%) received relaxation without
      sedation, and in 35 cases (42%), intubation was done without drugs. Drugs used
      for sedation/induction were ketamine in 22 (26%), midazolam in 14 (17%), propofol
      in 7 (8%), and etomidate in 3 cases (4%). Neuromuscular blockades used were
      rocuronium in 27 cases (32%), succinylcholine in 11 cases (13.5%), and atracurium
      in 5 cases (6%). Complications were noted in 16 cases (19%). CONCLUSIONS:
      Respiratory failure was found to be the main presenting complaint. Drugs for
      sedation and relaxation to facilitate ET intubation were underused.

PMID- 23114235
TI  - The complex association of race and leaving the pediatric emergency department
      without being seen by a physician.
AB  - OBJECTIVES: This study examined the influence of race and language on leaving the
      emergency department (ED) without complete evaluation and treatment (LWCET).
      METHODS: This retrospective, case-cohort study examined LWCET among patients
      discharged home from 2 EDs between March 2, 2009, and March 31, 2010. Race and
      language were obtained by family self-report. We also explored wait time to see a
      physician as an explanation of racial disparities. RESULTS: One thousand two
      hundred eighty-five (1.7%) of 76,931 ED encounters ended in LWCET. Factors
      increasing LWCET were high ED activity, low acuity, and medical assistance (MA)
      insurance. American Indian, biracial, African American, and Hispanic races were
      also associated with higher odds of LWCET among visits by MA insurance patients
      compared with those of white patients on private insurance. Restricting the
      analysis to visits by MA insurance patients, only American Indian race was
      associated with LWCET compared with white race. Visits by patients using an
      interpreter or speaking a language other than English at home had lower odds of
      ending in LWCET. Sensitivity analyses in subgroups confirmed these findings. We
      developed a measure of ED activity that correlated well with wait time to see a
      physician (correlation coefficient = 0.993; P < 0.001). Among non-LWCET visits,
      wait time to see a practitioner did not correlate with racial disparities in
      LWCET. CONCLUSIONS: Race, language, and insurance status interact to form a
      complex relationship with LWCET. Medical assistance insurance status appears to
      account for much of the excessive instances of LWCET seen in nonwhites. After
      restricting the analysis to MA insurance patients, only visits by American Indian
      patients had higher odds of LWCET compared with whites on MA insurance. Wait time
      to see a physician did not explain racial differences in LWCET.

PMID- 23114236
TI  - Ethnicity and reported pain scores among children with long-bone fractures
      requiring emergency care.
AB  - OBJECTIVES: Previous studies have shown that regular pain measurement improves
      pain management. As the diversity of patients seeking emergency care continues to
      grow, a better understanding of the potential differences in pain perception and
      analgesic needs among various cultural groups will be required. The purpose of
      this study was to describe the differences in pain scores reported among ethnic
      groups treated for a long-bone fracture. METHODS: A retrospective review of
      patients with a long-bone fracture treated in an urban pediatric emergency
      department during a 12-month period was performed. Pain scores were assessed
      using previously validated pain scales. RESULTS: Eight hundred eighty patients
      met our inclusion criteria. Wrist fracture was the most common type of fracture
      in our study. There were significant differences noted in reported pain scores.
      Patients identified as Hmong had the highest pain scores, and patients identified
      as Somali had the lowest pain scores reported. Patients with wrist fractures had
      the highest average pain score when compared with other types of fractures.
      Children with fractures requiring reduction in the emergency department had
      higher pain scores than those who had a fracture that did not require reduction.
      CONCLUSIONS: To our knowledge, this is the first study to investigate the
      relationships between ethnicity and pain scores reported in children treated
      emergently for a long-bone fracture.

PMID- 23114237
TI  - Emergency ultrasound in the detection of pediatric long-bone fractures.
AB  - BACKGROUND: Long-bone fractures represent one of the most commonly sustained
      injuries following trauma and account for nearly 4% of emergency department
      visits in the United States each year. These fractures are associated with a
      significant risk of bleeding and neurovascular compromise. Delays in their
      identification and treatment can lead to loss of limb and even death. Although
      emergency physicians currently rely predominantly on radiography for the
      examination of long-bone injuries, emergency ultrasound has several advantages
      over radiography and may be useful in the identification of long-bone fractures.
      Ultrasound is rapid, noninvasive, and cost-effective. Unlike radiography,
      ultrasound does not expose children to ionizing radiation, which has been linked
      to cancer. OBJECTIVE: The goal of this study was to assess the agreement between
      emergency physicians' and radiologists' final assessments of suspected long-bone
      fractures using emergency ultrasound and radiography, respectively, in the
      pediatric population. METHODS: This is a prospective study involving a
      convenience sample of pediatric patients (<18 years of age) who presented to the
      emergency department of a university-affiliated, level I trauma center between
      March 2008 and January 2009 with at least 1 suspected long-bone fracture.
      Suspected fractures were characterized by swelling, erythema, and localized pain.
      Patients who had a history of fracture, extremity deformity, orthopedic hardware
      in the traumatized area, or an open fracture were excluded from this study. Each
      investigator received limited, focused training in the use of ultrasonography for
      fracture identification and localization. This training consisted of a brief
      didactic session and video review of normal and fractured long-bones. RESULTS: A
      total of 53 subjects (mean age, 10.2 [SD, 3.8] years; 56.6% were male) were
      enrolled, which corresponded to 98 ultrasound examinations. Sixty-nine scans
      (70.4%) involved bones of the upper extremity, and 29 (29.6%) the lower
      extremity. Radiography identified a total of 43 fractures. The sensitivity and
      specificity of ultrasound in the detection of long-bone fractures were 95.3% (95%
      confidence interval [CI], 82.9%-99.2%) and 85.5% (95% CI, 72.8%-93.1%),
      respectively, and the positive and negative predictive values were 83.7% (95% CI,
      68.8%-92.2%) and 96% (95% CI, 84.9%-99.3%), respectively. Overall, ultrasound
      detected 100.0% of diaphyseal fractures and 27 (93.1%) of 29 end-of-bone or near
      joint fractures.Radiography revealed 6 displacements that met the published
      criteria for reduction, all of which were also revealed by ultrasound. The
      overall sensitivity and specificity for ultrasound identifying the need for
      reduction were 100.0% (95% CI, 51.7%-100.0%) and 97.3% (95% CI, 84.2%-99.9%),
      respectively, and positive and negative predictive values were 85.7% (95% CI,
      42.0%-99.2%) and 100.0% (95% CI, 88.0%-100.0%), respectively. CONCLUSIONS:
      Emergency department physician-performed focused ultrasound was more accurate in
      detecting diaphyseal fractures than in detecting fractures in the metaphysis
      and/or epiphysis. The high sensitivity and specificity of ultrasound in the
      detection of long-bone fractures and the need for reduction support the use of
      ultrasound in the evaluation of suspected long-bone fractures in children.

PMID- 23114238
TI  - Gartland type I supracondylar humerus fractures in children: is splint
      immobilization enough?
AB  - OBJECTIVE: The primary objective of this study was to determine if Gartland type
      I supracondylar humerus (SCH) fractures undergo significant displacement
      resulting in a change in management when treated with a long-arm splint.
      Secondary objectives included measured changes at follow-up in displacement
      and/or angulation. METHODS: This was a retrospective review of children who
      presented with elbow injuries to a children's hospital. Patients were included if
      they were diagnosed with a Gartland type I SCH fracture, managed with a long-arm
      splint, and had at least 1 follow-up visit 2 to 3 weeks from the emergency
      department visit. The primary outcome was the proportion of cases that required
      the placement of a circumferential cast and/or an operative intervention.
      Secondary outcomes included the proportion of cases with significant changes in
      displacement on any view, Baumann or the lateral humerocapitellar angle, and/or
      category of position of anterior humeral line relative to capitellum. RESULTS: Of
      804 elbow injuries that presented from 2003 to 2008, 53 patients met the
      inclusion criteria. The median age of the patients was 4.1 years (interquartile
      range, 3.4-6.1 years) years. Of the 53, there were no cases that required a
      change in management. One case had a change in the humerocapitellar angle, and
      another had a change of 1 category in position of the capitellum relative to the
      anterior humeral line. There were no other cases of significant changes in
      displacement or angulation. CONCLUSIONS: These data support that Gartland type I
      SCH fractures can be treated effectively with long-arm posterior splinting for
      the duration of therapy.

PMID- 23114239
TI  - Pediatric emergency department census during major sporting events.
AB  - OBJECTIVES: Our study attempted to evaluate the effects of major sporting events
      on the census of a pediatric emergency department (ED) in the United States
      specifically related to the National Football League Super Bowl, National
      Basketball Association (NBA) Finals, and Major League Baseball World Series.
      METHODS: We performed a retrospective data analysis of our pediatric ED census on
      the number of visits during major sporting events over a 5-year period. Data
      during the same period 1 week after the major sporting event were collected for
      comparison as the control. We evaluated the medians of 2-hour increments around
      the event start time. Subgroup analysis was performed for games involving the
      local sporting teams. RESULTS: Our results showed no significant difference in ED
      census during the sporting events, except in the post 6 to 8 hours of the NBA
      finals. Subgroup analysis of the Los Angeles Lakers showed the same significant
      findings in the post 6 to 8 hours of the NBA finals. CONCLUSIONS: No major
      difference in pediatric ED census is observed during the most major sporting
      events in the United States.

PMID- 23114240
TI  - Utilization of a pediatric observation unit for toxicologic ingestions.
AB  - OBJECTIVES: The objectives of this study were to evaluate the efficacy and
      utilization of an observation unit (OU) for admission of pediatric patients after
      a toxicologic ingestion; compare the characteristics and outcomes of patients
      admitted to the pediatric OU, inpatient (IP) service, and intensive care unit
      (ICU) after ingestions using retrospective chart review; and attempt to identify
      factors associated with unplanned IP admission after an OU admission. METHODS:
      This was a retrospective chart review of children seen in the emergency
      department (ED) after potentially toxic suspected ingestions and then admitted to
      the OU, IP service, or ICU from June 2003 to September 2007. RESULTS: One
      thousand twenty-three children were seen in the ED for ingestions: 18% were
      admitted to the OU, 15% to the IP service service, and 6% to the ICU. Observation
      unit patients had less mental status changes reported and were less frequently
      given medications while in the ED. Eighty-one percent of OU patients were
      admitted with poison center recommendation. Ninety-four percent of OU patients
      were discharged within 24 hours, and less than half of IP service/ICU patients
      were discharged that quickly. No significant associations were found between
      specific historical and physical examination or laboratory characteristics in the
      ED and the need for unplanned IP admission. CONCLUSIONS: Observation unit
      patients admitted after ingestions were young, typically ingested substances
      found in the home, and required observation according to poison center
      recommendations. Ninety-four percent were able to be discharged home within 24
      hours even after ingesting some of the most concerning substances such as central
      nervous system depressants, cardiac/antihypertension medications, hypoglycemics,
      and opiates. All OU patients did well without any adverse events reported. Many
      patients requiring prolonged observation after an ingestion, and who do not
      require ICU care, may be appropriate for OU management. This study suggests a
      potential underutilization of observation units in this setting.

PMID- 23114241
TI  - A new after-hours clinic model provides cost-saving, faster care compared with a
      pediatric emergency department.
AB  - OBJECTIVE: The objective of this study was to compare the charges and length of
      stay of demographically and clinically matched nonemergent patients managed in a
      new After-Hours Clinic (AHC) model versus a pediatric emergency department (PED).
      METHODS: Retrospective cross-sectional study conducted in a tertiary-care urban
      academic children's hospital. The AHC was off-site from the children's hospital
      emergency department. After-Hours Clinic patients were matched with PED patients
      for age, date and time of presentation, and chief complaint. The 95% confidence
      intervals for the difference in the means were used to compare the outcome
      variables of charges and length of stay. RESULTS: Of 471 patients seen at AHC in
      January 2008, 130 were matched to PED patients for date and time of presentation,
      age, and chief complaint, giving 260 study patients. There was no significant
      difference between AHC and PED patients in relationship to date and time of
      presentation, sex, age, and chief complaint. Comparing the length of stay and
      charges between AHC and PED patients revealed a significant difference in each.
      The patient-visit length-of-stay mean time for the AHC was 81.2 minutes less than
      the mean time for the PED (95.6 vs 176.8 minutes). The patient-visit mean charge
      for the AHC was $236.20 less than the mean charge for the PED ($226.00 vs
      $462.20). CONCLUSIONS: Our AHC model showed a significant reduction in length of
      stay and charges in compared demographically and clinically matched PED patients.
      This may be an effective model to help address emergency department overcrowding
      and promote patient safety.

PMID- 23114242
TI  - Clinical and economic impact of oral ondansetron for vomiting in a pediatric
      emergency department.
AB  - In this study, we determine the clinical impact of 1 dose of oral ondansetron for
      children with vomiting and evaluate the economic consequences of its use. The
      strategies compared were administering oral ondansetron in addition to oral
      rehydration therapy (group A) versus oral rehydration solution alone (group B) in
      children attended to for vomiting in a pediatric emergency department. The study
      population was 1871 children between 0 and 14 years of age treated for vomiting
      during a 2-year period (2009-2010). Outcome measures were need for intravenous
      rehydration, length of stay in the emergency department, return visits, and
      hospitalization. Estimates of the costs in the emergency department and
      hospitalization were derived from administrative databases. During the study
      period, 580 (31%) of 1871 patients received oral rehydration therapy. Oral
      ondansetron before oral rehydration solution was used in 109 (18.8%) of 580
      patients. An equal number of patients not receiving ondansetron were randomized
      and analyzed for comparison (group B). Patients of group A had a significantly
      decreased risk of hospitalization (relative risk, 0.22; 95% confidence interval,
      0.08-0.63) and intravenous rehydration (relative risk, 0.31; 95% confidence
      interval, 0.14-0.63), but there were no differences in the length of stay or
      return visits to the emergency department. There were no differences in the
      medical costs between both groups in the emergency department (US $22,078 vs US
      $21,987, respectively). The hospitalization cost was US $9600 for group A and US
      $25,079 for group B, providing a 73.7% saving. In conclusion, the administration
      of oral ondansetron to children with vomiting in the emergency department is
      clinically effective and results in significant economic savings.

PMID- 23114243
TI  - Cardiac troponin T as a screening test for myocarditis in children.
AB  - OBJECTIVE: The objective of this study was to define the test characteristics of
      cardiac troponin T (cTnT) in pediatric patients who presented with suspected
      myocarditis. METHODS: We performed a retrospective cohort study of all patients
      at a large urban children's hospital 21 years or younger who had a cTnT test sent
      for evaluation for myocarditis over a 13-month period. Patients were excluded if
      they had any history of heart disease or cardiac arrest before presentation, or
      the cTnT was sent for reasons other than concern for myocarditis. Positive cases
      of myocarditis were defined by characteristic pathology findings, magnetic
      resonance imaging results, or diagnosis of the attending cardiologist at time of
      discharge. RESULTS: Six hundred fifty-two patients had cTnT sent during the study
      period. Two hundred sixty were excluded because of prior history of heart
      disease, and 171 had the test sent for reasons other than concern for
      myocarditis. Of the 221 patients included in the study, 49 had an initial
      positive cTnT (>=0.01 ng/mL), whereas 172 had a negative test result. Eighteen
      cases of myocarditis were identified. All patients with myocarditis had an
      elevated cTnT at presentation. Using a cutoff value of 0.01 ng/mL or greater as a
      positive test, cTnT had a sensitivity of 100% (95% confidence interval [CI], 78%
      100%), with a negative predictive value of 100% (CI, 97%-100%), and a specificity
      of 85% (CI, 79%-89%), with positive predictive value of 37% (CI, 24%-52%), in the
      diagnosis of myocarditis. CONCLUSIONS: In children without preexisting heart
      disease, a cTnT level of less than 0.01 ng/mL can be used to exclude myocarditis.

PMID- 23114244
TI  - Nasopharyngeal airway pressures in bronchiolitis patients treated with high-flow
      nasal cannula oxygen therapy.
AB  - BACKGROUND: Heated, humidified, high-flow nasal cannula oxygen therapy (HHHFNC)
      has been used to improve ventilation in preterm infants. There are no data on
      airway pressures generated and efficacy in bronchiolitis. OBJECTIVE: The
      objective of this study was to determine nasopharyngeal (NP) pressures generated
      with HHHFNC therapy in bronchiolitis. METHODS: We conducted a prospective,
      observational study to measure NP pressures at varying flow rates of HHHFNC
      therapy in moderate to severe bronchiolitis. Vital signs, bronchiolitis severity
      scores, and oxygen saturation were also noted. RESULTS: Twenty-five patients were
      enrolled (mean, 78.1 [SD, 30.9] days; weight, 5.3 [SD, 1.1] kg). Nasopharyngeal
      pressures increased linearly with flow rates up to 6 L/min. Beyond 6 L/min,
      pressure increase was linear but less accelerated. On average, NP pressure
      increased by 0.45 cm H2O for each 1-L/min increase in flow rate. There were
      significant differences between pressures in open- and closed-mouth states for
      flow rates up to 6 L/min. At 6 L/min, the pressure in open-mouth state was 2.47
      cm H2O and that in closed-mouth state was 2.74 cm H2O (P < 0.001). Linear
      regression analysis revealed that only flow (not weight or gender) had an effect
      on generated pressure. Bronchiolitis severity scores improved significantly with
      HHHFNC therapy (pre: 14.5 [SD, 1.4], post: 10.4 [SD, 1.2]; P < 0.001).
      CONCLUSIONS: Increasing flow rates of HHHFNC therapy are associated with linear
      increases in NP pressures in bronchiolitis patients. Larger studies are needed to
      assess the clinical efficacy of HHHFNC therapy in bronchiolitis.

PMID- 23114245
TI  - The spectrum of group A streptococcal joint pathology in the acute care setting.
AB  - OBJECTIVES: Group A streptococcus (GAS) is a frequent cause of pediatric
      musculoskeletal infections including septic arthritis, acute rheumatic fever
      (ARF), and a more benign arthritis called post-streptococcal reactive arthritis.
      Children with painful joints are frequently evaluated in the acute care setting,
      and because the presentation of each of these entities is similar, the diagnosis
      can be difficult to make. Five cases of children with GAS arthridities are
      presented to demonstrate the spectrum of GAS-associated joint pathologies
      encountered in the acute care setting and also to discuss how GAS laboratory
      tests may assist in the evaluation and management of children presenting with a
      painful joint. METHODS: Five cases of GAS-associated joint pathology are
      presented. Evaluation of these patients was conducted using a diagnostic
      algorithm derived from a literature review of post-streptococcal reactive
      arthritis and ARF, as well as the current clinical practice guideline for the
      diagnosis and treatment of septic arthritis. RESULTS: The 5 cases presented
      include 1 case of transient synovitis, 2 cases of inflammatory synovitis, 1 case
      of septic arthritis, and 1 case of ARF. CONCLUSIONS: Determining the cause of
      joint pain in the acute care setting is challenging. The addition of the GAS
      laboratory tests to a diagnostic algorithm based on clinical examination and
      monitoring systemic inflammation can help to identify patients with ARF and
      septic arthritis in the acute care setting. In addition, GAS-specific laboratory
      tests may help to identify cases of nonseptic, non-ARF GAS joint pathology.

PMID- 23114246
TI  - Perception of medical care systems and stress responses in preschoolers'
      caregivers at a pediatric emergency department in Taiwan.
AB  - OBJECTIVES: This study was undertaken to understand caregivers' perception of
      medical care systems and their stress responses throughout their stay with
      preschoolers at a pediatric emergency department (ED). METHODS: Overall, 201
      preschoolers' caregivers in pediatric ED were recruited in this study. They were
      asked to answer self-made questionnaires regarding the perception of medical care
      systems and their stress responses immediately before preschoolers' release.
      RESULTS: The results show that caregivers with a low education or low income
      level were prone to exhibit greater appreciation for the efficiency of medical
      care systems and greater degree of anxiety for their lack of treatment and care
      knowledge than those of caregivers with a high education or high income level.
      Interestingly, caregivers older than 38 years reported greater emotional
      responses and physical exhaustion than did younger caregivers. Immigrant
      caregivers had higher emotional reaction and lower concentration than did
      Taiwanese caregivers. Paradoxically, caregivers undergoing over 3-time pediatric
      ED visits for observation expressed stronger stress reactions as compared with
      caregivers with less observation experiences. Not surprisingly, caregivers
      reported the highest emotional responses when their preschoolers were diagnosed
      as having very urgent degree in triage classification. Finally, caregivers'
      perception of "lack of family support" and "lack of treatment and care knowledge"
      correlated positively with all aspects of the stress responses. CONCLUSIONS:
      These results indicate that attention should be paid to the specific
      psychological weakness and need for the caregivers with certain demographic
      characteristics by the medical team in pediatric ED.

PMID- 23114247
TI  - Do children with high body mass indices have a higher incidence of emesis when
      undergoing ketamine sedation?
AB  - OBJECTIVES: The objective of this study was to determine if overweight children
      are more likely than normal-weight children to require ondansetron when
      undergoing ketamine sedation in a pediatric emergency department. METHODS:
      Patients between the ages of 2 and 18 years with an American Society of
      Anesthesiologists classification of I or II who underwent intravenous procedural
      sedation with ketamine with or without midazolam for uncomplicated forearm
      fracture reduction in an urban pediatric emergency department during the year
      2007 were included. A review of sedation records was conducted for each visit.
      Data collected included demographics, sedation time, and doses of medications
      administered. Body mass index (BMI) was calculated using an estimated height for
      the 50th percentile for age and sex. In 2007, all patients underwent procedural
      sedation per protocol. Per protocol, patients did not prophylactically receive
      ondansetron during procedural sedations. RESULTS: During the study period, 141
      patients were identified who met inclusion criteria. Of these, 110 had an
      estimated BMI less than 25 kg/m; 31 had an estimated BMI of 25 kg/m or greater.
      Ten patients (7.1%) received ondansetron. Patients in the high-BMI group were
      more likely to have received ondansetron than those in the normal-BMI group
      (16.1% vs 4.5%, P = 0.04). CONCLUSIONS: Our data suggest that pediatric patients
      with high BMIs are at greater risk for nausea or emesis during ketamine sedation.
      Clinicians should consider prophylactic administration of ondansetron to this
      group of patients before performing ketamine sedation.

PMID- 23114248
TI  - Educational interventions for intimate partner violence: guidance from survivors.
AB  - OBJECTIVE: Previous research suggests that health care providers' assumptions
      about the content and marketing of intimate partner violence (IPV) materials are
      not always correct and may do harm. This study sought to determine what mothers
      with histories of IPV identify as important information to communicate about IPV
      and how it should be presented in a pediatric emergency department. METHODS: This
      qualitative study used English- and Spanish-speaking focus groups for data
      collection and a grounded theory approach for data analysis. Initial focus groups
      elicited opinions on content, appearance, and location of IPV material. After
      data analysis, IPV posters were developed. Follow-up focus groups provided
      feedback on the posters. RESULTS: Ninety-nine mothers with histories of IPV
      participated in 8 initial and 4 follow-up focus groups. Women felt information
      should be presented in a positive, hopeful manner. Key information desired was
      signs of IPV, effects of childhood IPV exposure, and available resources. Spanish
      speaking groups desired that information that helps was available regardless of
      immigration status. Women cautioned that information regarding the effects of
      childhood IPV exposure should be presented in a nonjudgmental manner to minimize
      feelings of anger and guilt in mothers. Participants endorsed the distribution of
      IPV materials in many formats and locations but also worried that women might
      suffer retribution if perpetrators see IPV material. CONCLUSIONS: Passive
      educational interventions for IPV should present information about the signs of
      IPV, resources, and effects on children in a positive, hopeful manner. Materials
      directed toward Spanish-speaking victims should address the issue of immigration
      status.

PMID- 23114249
TI  - Emergency department transport rates of children from the scene of motor vehicle
      collisions: do booster seats make a difference?
AB  - BACKGROUND: Motor vehicle collisions (MVCs) are the leading cause of death and
      disability among children older than 1 year. Many states currently mandate all
      children between the ages of 4 and 8 years be restrained in booster seats. The
      implementation of a booster-seat law is generally thought to decrease the
      occurrence of injury to children. We hypothesized that appropriate restraint with
      booster seats would also cause a decrease in emergency department (ED) visits
      compared with children who were unrestrained. This is an important measure as ED
      visits are a surrogate marker for injury. OBJECTIVE: The main purpose of this
      study was to look at the rate of ED visits between children in booster seats
      compared with those in other or no restraint systems involved in MVCs. Injury
      severity was compared across restraint types as a secondary outcome of booster
      seat use after the implementation of a state law. METHODS: A prospective
      observational study was performed including all children 4 to 8 years old
      involved in MVCs to which emergency medical services was dispatched. Ambulance
      services used a novel on-scene computer charting system for all MVC-related
      encounters to collect age, sex, child-restraint system, Glasgow Coma Scale score,
      injuries, and final disposition. RESULTS: One hundred fifty-nine children were
      studied with 58 children (35.6%) in booster seats, 73 children in seatbelts alone
      (45.2%), and 28 children (19.1%) in no restraint system. 76 children (47.7%), 74
      by emergency medical services and 2 by private vehicle, were transported to the
      ED with no significant difference between restraint use (P = 0.534). Utilization
      of a restraint system did not significantly impact MVC injury severity. However,
      of those children who either died (n = 2) or had an on-scene decreased Glasgow
      Coma Scale score (n = 6), 75% (6/8) were not restrained in a booster seat.
      CONCLUSIONS: The use of booster-seat restraints does not appear to be associated
      with whether a child will be transported to the ED for trauma evaluation.

PMID- 23114250
TI  - Hemoptysis in children: a single institutional experience.
AB  - OBJECTIVES: The purpose of this study was to describe a single institutional
      experience with pediatric diffuse pulmonary hemorrhage, with an emphasis on
      etiology, clinical course, and outcome. METHODS: The medical records of pediatric
      patients admitted to Assaf Harofeh Medical Center between the years 2002 and 2011
      because of hemoptysis and pulmonary infiltrates on chest radiographs were
      retrospectively reviewed. RESULTS: Sixteen patients were identified. All the
      participants had respiratory complaints, and bloody cough was the presenting
      symptom in 11 patients. Twelve patients were admitted to the pediatric intensive
      care unit: 10 required mechanical ventilation, 9 had diffuse pulmonary
      infiltrates, and 8 required transfusions of blood products. Eight patients had an
      infectious disease (1 had tuberculosis). Two patients had severe coagulopathy.
      Three patients had diffuse bronchiectasis (1 had immunodeficiency). Cardiac
      failure was identified in 1 patient. Cocaine-induced pulmonary hemorrhage was
      identified in an adolescent. In 4 infants, the cause of pulmonary hemorrhage was
      not identified. Bronchoscopy and computed tomography were each performed in 9
      patients. Five patients died during the acute phase of the illness because of
      severe hypoxia and multiorgan failure. CONCLUSIONS: At our institution,
      hemoptysis is a rare but potentially life-threatening symptom. The etiology is
      heterogeneous. Clinical signs and chest radiographs are important for classifying
      the severity of the disease. Minor hemoptysis with focal findings on chest
      radiograph has a favorable short-term prognosis, with infectious diseases being
      involved in most cases.

PMID- 23114251
TI  - UK MPs demand more stringent regulation of medical devices across Europe.

PMID- 23114253
TI  - Diabetes death rates among youths aged <= 19 years--United States, 1968-2009.
AB  - Although diabetes mellitus most often is diagnosed in adulthood, it remains one
      of the most common serious chronic diseases of childhood. Youths with diabetes
      are at risk for diabetes-related mortality because of acute complications that
      can result from the condition, including diabetic ketoacidosis and hypoglycemia.
      In the United States in 2010, an estimated 215,000 persons aged <= 19 years had
      diagnosed diabetes. Medical care for diabetes has improved considerably in recent
      decades, leading to improved survival rates. However, recent trends in diabetes
      death rates among youths aged <10 years and 10-19 years in the United States have
      not been reported. To assess these trends, CDC analyzed data from the National
      Vital Statistics System for deaths in the United States with diabetes listed as
      the underlying cause during 1968-2009. This report highlights the results of that
      analysis, which found that diabetes-related mortality decreased 61%, from an
      annual rate of 2.69 per million for the period 1968-1969 to a rate of 1.05 per
      million in 2008-2009. The percentage decrease was greater among youths aged <10
      years (78%) than among youths aged 10-19 years (52%). These findings demonstrate
      improvements in diabetes mortality among youths but also indicate a need for
      continued improvement in diabetes diagnosis and care.

PMID- 23114252
TI  - Linkage disequilibrium analysis reveals an albuminuria risk haplotype containing
      three missense mutations in the cubilin gene with striking differences among
      European and African ancestry populations.
AB  - BACKGROUND: A recent meta-analysis described a variant (p.Ile2984Val) in the
      cubilin gene (CUBN) that is associated with levels of albuminuria in the general
      population and in diabetics. METHODS: We implemented a Linkage Disequilibrium
      (LD) search with data from the 1000 Genomes Project, on African and European
      population genomic sequences. RESULTS: We found that the p.Ile2984Val variation
      is part of a larger haplotype in European populations and it is almost absent in
      west Africans. This haplotype contains 19 single nucleotide polymorphisms (SNPs)
      in very high LD, three of which are missense mutations (p.Leu2153Phe,
      p.Ile2984Val, p.Glu3002Gly), and two have not been previously reported. Notably,
      this European haplotype is absent in west African populations, and the frequency
      of each individual polymorphism differs significantly in Africans. CONCLUSIONS:
      Genotyping of these variants in existing African origin sample sets coupled to
      measurements of urine albumin excretion levels should reveal which is the most
      likely functional candidate for albuminuria risk. The unique haplotypic structure
      of CUBN in different populations may leverage the effort to identify the
      functional variant and to shed light on evolution of the CUBN gene locus.

PMID- 23114254
TI  - Evaluation of 11 commercially available rapid influenza diagnostic tests--United
      States, 2011-2012.
AB  - Accurate diagnosis of influenza is critical for clinical management, infection
      control, and public health actions to minimize the burden of disease.
      Commercially available rapid influenza diagnostic tests (RIDTs) that detect the
      influenza virus nucleoprotein (NP) antigen are widely used in clinical practice
      for diagnosing influenza because they are simple to use and provide results
      within 15 minutes; however, there has not been a recent comprehensive analytical
      evaluation of available RIDTs using a standard method with a panel of
      representative seasonal influenza viruses. This report describes an evaluation of
      11 Food and Drug Administration (FDA)-cleared RIDTs using 23 recently circulating
      influenza viruses under identical conditions in a laboratory setting to assess
      analytical performance. Most RIDTs detected viral antigens in samples with the
      highest influenza virus concentrations, but detection varied by virus type and
      subtype at lower concentrations. Clinicians should be aware of the variability of
      RIDTs when interpreting negative results and should collect test samples using
      methods that can maximize the concentration of virus antigen in the sample, such
      as collecting adequate specimens using appropriate methods in the first 24-72
      hours after illness onset. The study design described in this report can be used
      to evaluate the performance of RIDTs available in the United States now and in
      the future.

PMID- 23114255
TI  - Current tobacco use and secondhand smoke exposure among women of reproductive age
      -14 countries, 2008-2010.
AB  - Tobacco use and secondhand smoke (SHS) exposure in reproductive-aged women can
      cause adverse reproductive health outcomes, such as pregnancy complications,
      fetal growth restriction, preterm delivery, stillbirths, and infant death. Data
      on tobacco use and SHS exposure among reproductive-aged women in low- and middle
      income countries are scarce. To examine current tobacco use and SHS exposure in
      women aged 15-49 years, data were analyzed from the 2008-2010 Global Adult
      Tobacco Survey (GATS) from 14 low- and middle-income countries: Bangladesh,
      Brazil, China, Egypt, India, Mexico, Philippines, Poland, Russia, Thailand,
      Turkey, Ukraine, Uruguay, and Vietnam. The results of this analysis indicated
      that, among reproductive-aged women, current tobacco smoking ranged from 0.4% in
      Egypt to 30.8% in Russia, current smokeless tobacco use was <1% in most
      countries, but common in Bangladesh (20.1%) and India (14.9%), and SHS exposure
      at home was common in all countries, ranging from 17.8% in Mexico to 72.3% in
      Vietnam. High tobacco smoking prevalence in some countries suggests that
      strategies promoting cessation should be a priority, whereas low prevalence in
      other countries suggests that strategies should focus on preventing smoking
      initiation. Promoting cessation and preventing initiation among both men and
      women would help to reduce the exposure of reproductive-aged women to SHS.

PMID- 23114256
TI  - Global routine vaccination coverage, 2011.
AB  - In 1974, the World Health Organization (WHO) established the Expanded Programme
      on Immunization (EPI) to ensure all children had access to routinely recommended
      vaccines. Initially, those vaccines were limited to bacille Calmette-Guerin
      vaccine (BCG), diphtheria-tetanus-pertussis vaccine (DTP), oral poliovirus
      vaccine, and measles-containing vaccine (MCV). Global coverage with the third
      dose of DTP (DTP3) increased from <5% in 1974 to 79% by 2005. However, one fifth
      of the world's children, especially those in low-income countries, still were not
      fully vaccinated during the first year of life with the four traditional EPI
      vaccines. In 2005, WHO and the United Nations Children's Fund (UNICEF) developed
      the Global Immunization Vision and Strategy (GIVS) to improve national
      immunization programs and decrease vaccine-preventable disease-associated
      morbidity and mortality. A goal was to reach a sustained national DTP3 coverage
      of 90% in all countries. This report summarizes global routine vaccination
      coverage during 2011. An estimated 83% of infants worldwide received at least 3
      doses of DTP in 2011, similar to coverage in 2009 (82%) and 2010 (85%). Among 194
      WHO member states, 130 (67%) achieved >= 90% national DTP3 coverage. More than
      half of all incompletely vaccinated children (i.e., those who did not receive
      DTP3) lived in one of three countries: India (32%), Nigeria (14%), and Indonesia
      (7%). Strengthening routine immunization services, especially in countries with
      the greatest number of undervaccinated children, should be a global priority to
      help achieve the fourth Millennium Development Goal of reducing mortality among
      children aged <5 years by two thirds from 1990 to 2015.

PMID- 23114257
TI  - COPD mortality rates in Andalusia, Spain, 1975-2010: a joinpoint regression
      analysis.
AB  - OBJECTIVES: To describe chronic obstructive pulmonary disease (COPD) mortality
      rates in Andalusia, Spain, between 1975 and 2010 using a joinpoint regression
      analysis. DESIGN: Mortality figures for Andalusian residents aged >40 years from
      1975 to 2010 were obtained from the National  Institute of Statistics. Causes of
      death were classified based on the 8th, 9th and 10th revisions of the
      International Classification of Diseases. Crude, standardised (SMR) and 40- to 70
      year truncated mortality rates were calculated. Trends were analysed using
      joinpoint regression analysis  to identify significant trend changes, and an
      annual percentage of change (APC) was computed from each trend. RESULTS:
      Mortality rates showed a downward trend for both sexes. The SMR ranged from 109.9
      to 98.0 deaths/100 000 males, and between 35.8 and 12.0 deaths/100 000 females. 
      An increase in the average age at death for men and women with COPD was also
      observed. Both sexes experienced an increase in SMR in the early 1980s, although
      female mortality rates began to decline in 1985 (APC -5.8% thereafter), whereas
      those for males remained high until 1998 (APC  -4% thereafter). CONCLUSIONS: COPD
      mortality remains higher in male than female inhabitants of Andalusia. These
      rates have decreased following different sex- and age-dependent patterns.

PMID- 23114259
TI  - An interacting dipole model to explore broadband transverse optical binding.
AB  - The demonstration of optical binding of micro-particles placed in intense optical
      fields has resulted in unique and exciting prospects for studying new forms of
      condensed matter. The ability to tailor optical fields in the spatial and
      temporal domains elicits the possibility of creating novel condensed matter with
      the structure controlled by tailoring the optical field. Here, we theoretically
      calculate the transverse optical binding forces for nanoparticles within
      monochromatic and broadband optical fields. We demonstrate the decrease in
      amplitude of the optical binding forces for broadband fields as a function of
      inter-particle separation and attribute the effect to the averaging effect of
      spectrally dependent optical forces. We also examine multiple particle optically
      bound systems and use the interacting dipole method to find self-organized
      positions for six and ten particles illuminated by a monochromatic plane wave.

PMID- 23114258
TI  - Acute risk for hepatitis E virus infection among HIV-1-positive pregnant women in
      central Africa.
AB  - BACKGROUND: Hepatitis E virus (HEV), an enterically transmitted pathogen, is
      highly endemic in several African countries. Pregnant women are at particularly
      high risk for acute or severe hepatitis E. In Gabon, a central African country,
      the prevalence of antibodies to HEV among pregnant women is 14.1%. Recent studies
      have demonstrated unusual patterns of hepatitis E (chronic hepatitis, cirrhosis)
      among immunodeficient patients. FINDINGS: We investigated the prevalence of
      antibodies to HEV among pregnant women infected with HIV-1 or HTLV-1 in Gabon. Of
      243 samples collected, 183 were positive for HIV-1 and 60 for HTLV-1; 16 women
      (6.6%) had IgG antibodies to HEV. The seroprevalence was higher among HIV-1
      infected women (7.1%) than HTLV-1-infected women (5.0%). Moreover, the HIV-1
      viral load was significantly increased (p <= 0.02) among women with past-HEV
      exposure (1.3E+05 vs 5.7E+04 copies per ml), whereas no difference was found in
      HTLV-1 proviral load (9.0E+01 vs 1.1E+03 copies per ml). CONCLUSIONS: These data
      provide evidence that HIV-1-infected women are at risk for acute or severe
      infection if they are exposed to HEV during pregnancy, with an increased viral
      load.

PMID- 23114260
TI  - Mindfulness-based cognitive therapy in obsessive-compulsive disorder - a
      qualitative study on patients' experiences.
AB  - BACKGROUND: Cognitive behavioral therapy (CBT) with exposure and response
      prevention (ERP) is the first-line treatment for patients with obsessive
      compulsive disorder (OCD). However, not all of them achieve remission on a
      longterm basis. Mindfulness-based cognitive therapy (MBCT) represents a new 8
      week group therapy program whose effectiveness has been demonstrated in various
      mental disorders, but has not yet been applied to patients with OCD. The present
      pilot study aimed to qualitatively assess the subjective experiences of patients
      with OCD who participated in MBCT. METHOD: Semi-structured interviews were
      conducted with 12 patients suffering from OCD directly after 8 sessions of a
      weekly MBCT group program. Data were analyzed using a qualitative content
      analysis. RESULTS: Participants valued the treatment as helpful in dealing with
      their OCD and OCD-related problems. Two thirds of the patients reported a decline
      in OCD symptoms. Benefits included an increased ability to let unpleasant
      emotions surface and to live more consciously in the present. However,
      participants also discussed several problems. CONCLUSION: The data provide
      preliminary evidence that patients with OCD find aspects of the current MBCT
      protocol acceptable and beneficial. The authors suggest to further explore MBCT
      as a complementary treatment strategy for OCD.

PMID- 23114261
TI  - The in vitro study of ursolic acid and oleanolic acid inhibiting cariogenic
      microorganisms as well as biofilm.
AB  - OBJECTIVE: The aim of this study was to examine the effect of ursolic acid (UA)
      and oleanolic acid (OA), triterpenoid compounds that are isolated from many
      edible and medicinal plants, on cariogenic microorganisms and biofilms. METHODS:
      A microtitre plate dilution assay was used to determine the minimum inhibitory
      concentration (MIC) and minimum bactericidal concentration (MBC) of UA and OA
      against two Actinomyces spp. and four Streptococcus spp. The antibacterial
      activity of UA and OA was assessed by crystal violet staining, scanning electron
      microscopy (SEM) and confocal laser scanning microscopy (CLSM). RESULTS: UA and
      OA displayed differential antibacterial activities against the six tested
      bacteria, with UA showing greater antibacterial activity than OA. Furthermore,
      the two drugs had greater antibacterial activity against Actinomyces spp. than
      Streptococcus spp. UA and OA at 1/4 MIC can reduce bacterial biofilm formation,
      whereas higher UA concentrations displayed antibacterial activity against
      Actinomyces viscosus and Streptococcus mutans in mature biofilms. For instance,
      2.0 mg ml(-1) UA was sufficient to kill an A. viscosus biofilm. CONCLUSIONS: UA
      and OA inhibit the growth of cariogenic microorganisms, which suggests that UA
      and OA have considerable potential as antibacterial agents for dental caries
      prevention.

PMID- 23114262
TI  - Chronic hepatitis B and C co-infection increased all-cause mortality in HAART
      naive HIV patients in Northern Thailand.
AB  - A total of 755 highly active antiretroviral therapy (HAART)-naive HIV-infected
      patients were enrolled at a government hospital in Thailand from 1 June 2000 to
      15 October 2002. Census dateo f survival was on 31 October 2004 or the date of
      HAART initiation. Of 700 (92.6%) patients with complete data, the prevalence of
      hepatitis B virus (HBV) surface antigen and anti-hepatitis C virus (HCV) antibody
      positivity was 11.9% and 3.3%, respectively. Eight (9.6%) HBV co-infected
      patients did not have anti-HBV core antibody (anti-HBcAb). During 1166.7 person
      years of observation (pyo), 258 (36.9%) patients died [22.1/100 pyo, 95%
      confidence interval (CI) 16.7-27.8]. HBV and probably HCV co-infection was
      associated with a higher mortality with adjusted hazard ratios (aHRs) of 1.81
      (95% CI 1.30-2.53) and 1.90 (95% CI0.98-3.69), respectively. Interestingly, HBV
      co-infection without anti-HBc Ab was strongly associated with death (aHR 6.34,
      95% CI 3.99-10.3). The influence of hepatitis co-infection on the natural history
      of HAART-naive HIV patients requires greater attention.

PMID- 23114263
TI  - Improvement of primary stability in ACL reconstruction by mesh augmentation of an
      established method of free tendon graft fixation. A biomechanical study on a
      porcine model.
AB  - PURPOSE: The aim of the present study was to compare primary stability in ACL
      reconstruction and ultimate load to failure of a mesh augmented hamstring tendon
      graft fixed with two cross pins to established hamstrings and bone-patellar
      tendon-bone (BTB) graft fixation methods. METHODS: Forty fresh porcine femora
      were divided into four groups: (A): BTB graft fixed with two RigidFix(r) pins,
      (B): hamstring tendon graft fixed with a Milagro(r) interference screw, (C):
      hamstring tendon graft fixed with two RigidFix(r) pins, and (D): hamstring tendon
      graft augmented with Ultrapro(r) mesh fixed with two RigidFix(r) pins. Each graft
      underwent cyclic loading in tension and load to failure. Elastic and plastic
      displacements were measured by 3-dimensional digital image correlation. Groups
      were compared by one-way ANOVA and Tukey-Kramer post-hoc tests. RESULTS: After
      1000 cycles, the mean plastic displacement was lowest in the BTB graft (p <
      0.001). Plastic displacement was significantly lower in the mesh augmented group
      compared to the plain hamstring graft and the Milagro screw group (p < 0.05).
      Load to failure was highest in the mesh-augmented group; significant to the
      hamstring tendon (p = 0.023). CONCLUSION: Although the BTB-graft represented the
      most stable construct against plastic displacement in our study, mesh
      augmentation of free tendon grafts significantly increased primary stability and
      reduced plastic displacement of femoral cross pin fixation. This new augmentation
      device may better protect the hamstrings graft from secondary elongation during
      postoperative rehabilitation. CLINICAL RELEVANCE: Mesh augmentation seems to be
      an effective technique to stabilise free hamstring tendon autografts during
      postoperative rehabilitation with significant reduction of graft slippage.

PMID- 23114265
TI  - Percutaneous endoscopic gastrostomy in the open abdomen patient.
AB  - Nutrition support of critically ill patients is an integral element to their
      multimodal care. We describe the placement of a percutaneous endoscopic
      gastrostomy (PEG) for long-term enteral access in a patient with an open abdomen.
      To our knowledge, this is the third successfully reported case that demonstrates
      the viability of PEG in this uncommon population. In critically ill and
      malnourished surgical patients with contraindications for immediate abdominal
      closure, PEG should be strongly considered as a procedure for enteral feedings. 

PMID- 23114264
TI  - Y-site Compatibility of Intravenous Drugs With Parenteral Nutrition.

PMID- 23114266
TI  - Do we need to monitor cardiac output during major surgery?

PMID- 23114268
TI  - Highlight--small genomes for the swift: of flight and intron size.

PMID- 23114269
TI  - Management of the access site after transradial percutaneous procedures:
      literature overview.
AB  - The transradial approach (TRA) is emerging as a promising strategy to improve the
      safety of percutaneous coronary diagnostic or interventional procedures.
      Nevertheless, a series of specific complications related to the radial access
      have been described so that their prevention and optimal management is clinically
      relevant. In this article, the types of access-related vascular complications
      potentially occurring after TRA and their possible management are described. In
      particular, the vascular complications have been classified in three groups
      according to the main pathogenetic mechanism: thrombotic, hemorrhagic and
      nonthrombotic nonhemorrhagic. Moreover, a practical operative protocol for prompt
      diagnosis and treatment has been proposed.

PMID- 23114270
TI  - Remote ischemic conditioning:  the cardiologist's perspective.
AB  - Early and successful restoration of myocardial reperfusion following an ischemic
      event is the most effective strategy to reduce final infarct size and improve
      clinical outcome. However, revascularization per se may induce further myocardial
      damage by myocardial ischemia-reperfusion injury and worsen clinical outcome.
      Therefore, new therapeutic strategies are required to protect the myocardium
      against ischemia-reperfusion injury in patients with coronary artery disease.
      Remote ischemic conditioning (RIC) by brief nonlethal episodes of ischemia and
      reperfusion to an organ or tissue remote from the heart activates innate
      cardioprotective mechanisms. The discovery that RIC can be performed
      noninvasively using a blood pressure cuff on the upper arm to induce brief
      episodes of limb ischemia and reperfusion has facilitated the translation of RIC
      into the clinical arena. Whereas some trials have shown contradictory results,
      recently published proof-of-concept clinical studies have reported encouraging
      results with RIC. Large-scale multicenter clinical trials are needed to establish
      the role of RIC in the current clinical practice. At present, the use of RIC in
      acute coronary syndromes seems particularly attractive due to its potential in
      ambulance application and apparent dramatic reduction in infarct size in the
      patients with the largest infarcts. Cardiac arrest and stroke represent ischemia
      reperfusion disorders where RIC has further potential to improve outcome beyond
      rapid revascularization alone.

PMID- 23114271
TI  - Risk factors for atrial fibrillation recurrence: a literature review.
AB  - Atrial fibrillation is the most common arrhythmia managed in clinical practice
      and it is associated with an increased risk of mortality, stroke and peripheral
      embolism. Unfortunately, the incidence of atrial fibrillation recurrence ranges
      from 40 to 50%, despite the attempts of electrical cardioversion and the
      administration of antiarrhythmic drugs. In this review, the literature data about
      predictors of atrial fibrillation recurrence are highlighted, with special regard
      to clinical, therapeutic, biochemical, ECG and echocardiographic parameters after
      electrical cardioversion and ablation. Identifying predictors of success in
      maintaining sinus rhythm after cardioversion or ablation may allow a better
      selection of patients to undergo these procedures. The aim is to reduce
      healthcare costs and avoid exposing patients to unnecessary procedures and
      related complications. Recurrent atrial fibrillation depends on a combination of
      several parameters and each patient should be individually assessed for such a
      risk of recurrence. 

PMID- 23114272
TI  - Valvular regurgitations may increase risk of arrhythmias in Nigerians with
      hypertensive heart failure.
AB  - BACKGROUND: Hypertensive heart disease (HHD) is the commonest cause of sudden
      cardiac death among Nigerians. A high frequency and early onset of valvular
      regurgitations (VHD) in hypertensives, and greater concentric hypertrophy are
      also common in that population. AIMS AND METHODS: To further investigate the
      relationship between VHD and cardiac arrhythmias and their correlates seen in the
      hypertensive spectrum and to test the hypothesis that VHD predisposes to cardiac
      arrhythmias in hypertensive heart failure (HHF). HHF patients (n = 14), HHD
      patients n = 23, and normotensive controls (n = 9) all underwent 24 h
      electrocardiogram Holter monitoring as well as two-dimensional and Doppler
      echocardiography. Participants in each patient category were classified according
      to the presence and severity of VHD or its absence (NVHD). RESULTS: There were
      statistically significant differences in the mean supraventricular tachycardia
      (SVT) (P < 0.001 analysis of variance; ANOVA), the mean and median frequency of
      ventricular tachycardia episodes (P < 0.02 ANOVA), and couplets (P = 0.0002
      ANOVA) between groups. HHF-VHD always had more SVT (81/24 versus 4.4/24 h; P =
      0.016) and ventricular arrhythmias 69/24 versus 34/24 h (P < 0.02) than HHF-NVHD.
      Multivalvular regurgitations (three or more valves), higher left ventricular mass
      index (g/m2) [274 (24) versus 191(19); P < 0.001 ANOVA], and lower ejection
      fraction (EF; %) [29(3) versus 53(14)] in HHF-VHD were arrhythmogenic. Mean
      ventricular tachycardia/triplet frequency/24 h were HHF-VHD 69, HHF-NVHD 39, HHD
      VHD 0.3, HHD-NVHD 6, and controls 0.2 (P < 0.02 ANOVA). Compared with 35% (10/27)
      of all VHD, 15.7% (3/19) of all NVHD participants had nonsustained ventricular
      tachycardia. The number of regurgitant valves was positively correlated with the
      frequency of the Lown class of the arrhythmias 0-IVB (r = 0.42, P = 0.003) and to
      ventricular tachycardia (r = 0.3, P = 0.04) (both n = 46). CONCLUSION: Left
      ventricular hypertrophy (LVH) increased arrhythmias. But multivalvular
      regurgitations predisposes to greater SVT and complex ventricular arrhythmias,
      especially in HHF. Low EF and concentric LVH are correlates.

PMID- 23114273
TI  - Spectral cross-correlation as a supervised approach for the analysis of complex
      Raman datasets: the case of nanoparticles in biological cells.
AB  - Spectral cross-correlation is introduced as a methodology to identify the
      presence and subcellular distribution of nanoparticles in cells. Raman microscopy
      is employed to spectroscopically image biological cells previously exposed to
      polystyrene nanoparticles, as a model for the study of nano-bio interactions. The
      limitations of previously deployed strategies of K-means clustering analysis and
      principal component analysis are discussed and a novel methodology of spectral
      cross-correlation analysis is introduced and compared with the performance of
      classical least squares analysis, in both unsupervised and supervised modes. The
      previous study demonstrated the feasibility of using Raman spectroscopy to map
      cells and identify polystyrene nanoparticles in a lipid rich environment, which
      is suggestive of the membrane rich endoplasmic reticulum. However, short comings
      in identification of all nanoparticle signatures in the cell using K-means
      clustering are apparent, as highlighted by principal component analysis of the
      identified clusters which demonstrates that K-means clustering does not identify
      all regions where spectral signatures of the nanoparticles are evident. Thus, two
      more sophisticated analytical approaches to the extraction of the nanoparticle
      signatures from the Raman spectral datasets, namely classical least squares
      analysis and cross-correlation analysis, were employed and are demonstrated to
      improve the identification of spectroscopic signatures characteristic of
      polystyrene nanoparticles in a cellular environment. Additionally, to investigate
      the local biochemical environment in which the nanoparticles are trafficked, a
      pure spectrum of 3-sn-phosphatidyl ethanolamine was cross-correlated against the
      Raman dataset, further suggesting the particles are indeed localized in a lipid
      rich environment. Furthermore, to demonstrate the robustness and versatility of
      the analysis method, a spectrum of pure RNA was used to demonstrate that a
      differentiation could be made between DNA of the nucleus and RNA of the nucleolus
      using the supervised spectral cross-correlation technique.

PMID- 23114274
TI  - Circuit architecture explains functional similarity of bacterial heat shock
      responses.
AB  - Heat shock response is a stress response to temperature changes and a consecutive
      increase in amounts of unfolded proteins. To restore homeostasis, cells
      upregulate chaperones facilitating protein folding by means of transcription
      factors (TFs). We here investigate two heat shock systems: one characteristic to
      gram negative bacteria, mediated by transcriptional activator sigma(32) in E.
      coli, and another characteristic to gram positive bacteria, mediated by
      transcriptional repressor HrcA in L. lactis. We construct simple mathematical
      models of the two systems focusing on the negative feedbacks, where free
      chaperones suppress sigma(32) activation in the former, while they activate HrcA
      repression in the latter. We demonstrate that both systems, in spite of the
      difference at the TF regulation level, are capable of showing very similar heat
      shock dynamics. We find that differences in regulation impose distinct
      constraints on chaperone-TF binding affinities: the binding constant of free
      sigma(32) to chaperone DnaK, known to be in 100 nM range, set the lower limit of
      amount of free chaperone that the system can sense the change at the heat shock,
      while the binding affinity of HrcA to chaperone GroE set the upper limit and have
      to be rather large extending into the micromolar range.

PMID- 23114275
TI  - Micro-macro-discrepancies in nonlinear microrheology: I. Quantifying mechanisms
      in a suspension of Brownian ellipsoids.
AB  - Active and nonlinear microrheology experiments involve a colloidal probe that is
      forced to move within a material, with the goal of recovering  the nonlinear
      rheological response properties of the material. Various  mechanisms cause
      discrepancies between the nonlinear rheology measured microrheologically and
      macroscopically, including direct probe-bath collisions, the Lagrangian
      unsteadiness experienced by the material elements, and the spatially
      inhomogeneous and rheologically mixed strain field set up around the probe. Here,
      we perform computational nonlinear microrheology experiments, in which a
      colloidal probe translates through a dilute suspension of Brownian ellipsoids,
      whose results we compare against analogous computational experiments on the
      macroscopic shear rheology of the same model material. The quantitative impact of
      each of the mechanisms for micro-macro-discrepancy can thus be computed directly,
      with additional computational experiments performed where the processes in
      question are 'turned off'. We show that all three discrepancy mechanisms impact
      the microrheological measurement quantitatively, and that none can be neglected.
      This motivates a search for microrheological probes whose geometry or forcing is
      optimized to minimize these impacts, which we present in a companion article.

PMID- 23114276
TI  - Mutagenicity and antimutagenicity of (-)-hinokinin a trypanosomicidal compound
      measured by Salmonella microsome and comet assays.
AB  - BACKGROUND: The dibenzylbutyrolactone lignan (-)-hinokinin (HK) was derived by
      partial synthesis from (-)-cubebin, isolated from the dry seeds of the pepper,
      Piper cubeba. Considering the good trypanosomicidal activity of HK and recalling
      that natural products are promising starting points for the discovery of novel
      potentially therapeutic agents, the aim of the present study was to investigate
      the (anti) mutagenic/ genotoxic activities of HK. METHODS: The mutagenic/
      genotoxic activities were evaluated by the Ames test on Salmonella typhimurium
      strains TA98, TA97a, TA100 and TA102, and the comet assay, so as to assess the
      safe use of HK in the treatment of Chagas' disease. The antimutagenic
      /antigenotoxic potential of HK were also tested against the mutagenicity of a
      variety of direct and indirect acting mutagens, such as 4- nitro-o
      phenylenediamine (NOPD), sodium azide (SA), mitomycin C (MMC), benzo[a]pyrene
      (B[a]P), aflatoxin B1 (AFB1), 2-aminoanthracene (2-AA) and 2-aminofluorene (2
      AF), by the Ames test, and doxorubicin (DXR) by the comet assay. RESULTS: The
      mutagenicity/genotoxicity tests showed that HK did not induce any increase in the
      number of revertants or extent of DNA damage, demonstrating the absence of
      mutagenic and genotoxic activities. On the other hand, the results on the
      antimutagenic potential of HK showed a strong inhibitory effect against some
      direct and indirect-acting mutagens. CONCLUSIONS: Regarding the use of HK as an
      antichagasic drug, the absence of mutagenic effects in animal cell and bacterial
      systems is encouraging. In addition, HK may be a new potential antigenotoxic /
      antimutagenic agent from natural sources. However, the protective activity of HK
      is not general and varies with the type of DNA damage-inducing agent used.

PMID- 23114277
TI  - Phenotypic and genetic characterization of Dunaliella (Chlorophyta) from Indian
      salinas and their diversity.
AB  - BACKGROUND: The genus Dunaliella (Class - Chlorophyceae) is widely studied for
      its tolerance to extreme habitat conditions, physiological aspects and many
      biotechnological applications, such as a source of carotenoids and many other
      bioactive compounds. Biochemical and molecular characterization is very much
      essential to fully explore the properties and possibilities of the new isolates
      of Dunaliella. In India, hyper saline lakes and salt pans were reported to bloom
      with Dunaliella spp. However, except for the economically important D. salina,
      other species are rarely characterized taxonomically from India. Present study
      was conducted to describe Dunaliella strains from Indian salinas using a combined
      morphological, physiological and molecular approach with an aim to have a better
      understanding on the taxonomy and diversity of this genus from India. RESULTS:
      Comparative phenotypic and genetic studies revealed high level of diversity
      within the Indian Dunaliella isolates. Species level identification using
      morphological characteristics clearly delineated two strains of D. salina with
      considerable beta-carotene content (>20 pg/cell). The variation in 18S rRNA gene
      size, amplified with MA1-MA2 primers, ranged between ~1800 and ~2650 base pairs,
      and together with the phylogeny based on ITS gene sequence provided a pattern,
      forming five different groups within Indian Dunaliella isolates. Superficial
      congruency was observed between ITS and rbcL gene phylogenetic trees with
      consistent formation of major clades separating Indian isolates into two distinct
      clusters, one with D. salina and allied strains, and another one with D. viridis
      and allied strains. Further in both the trees, few isolates showed high level of
      genetic divergence than reported previously for Dunaliella spp. This indicates
      the scope of more numbers of clearly defined/unidentified species/sub-species
      within Indian Dunaliella isolates. CONCLUSION: Present work illustrates Indian
      Dunaliella strains phenotypically and genetically, and confirms the presence of
      not less than five different species (or sub-species) in Indian saline waters,
      including D. salina and D. viridis. The study emphasizes the need for a combined
      morphological, physiological and molecular approach in the taxonomic studies of
      Dunaliella.

PMID- 23114279
TI  - Mode expansion for the density profiles of crystal-fluid interfaces: hard spheres
      as a test case.
AB  - We present a technique for analyzing the full three-dimensional density profiles
      of planar crystal-fluid interfaces in terms of density modes. These density modes
      can also be related to crystallinity order parameter profiles which are used in
      coarse-grained, phase field type models of the statics and dynamics of crystal
      fluid interfaces and are an alternative to crystallinity order parameters
      extracted from simulations using local crystallinity criteria. We illustrate our
      results for the hard sphere system using finely resolved, three-dimensional
      density profiles from a density functional theory of fundamental measure type.

PMID- 23114278
TI  - The common Arg389gly ADRB1 polymorphism affects heart rate response to the ultra
      short-acting beta(1) adrenergic receptor antagonist esmolol in healthy
      individuals.
AB  - The beta1-adrenergic receptor (beta1AR) Arg389Gly polymorphism affects responses
      to orally administered beta1AR antagonists (beta-blockers) in vivo. However, the
      effect of this polymorphism on the early heart rate response to beta-blockers has
      not been evaluated. The aim of this study was to determine the effect of the
      Arg389Gly polymorphism on the inhibition of exercise-induced tachycardia by
      esmolol, an ultra-short-acting intravenously administered beta1AR antagonist.
      Healthy nonsmoking White individuals were enrolled on the basis of their ADRB1
      genotype, including carriers of 0, 1 or 2 Arg389 alleles (n=9 in each group,
      total 27, 18 men). Placebo and esmolol were infused consecutively for 10 min
      each, separated by 30 min. At the end of each infusion, participants performed
      dynamic handgrip exercise. Heart rate and blood pressure were compared among
      three ADRB1 genotypes. Carriers of 0, 1, or 2 Arg389 alleles varied significantly
      in both exercise-induced tachycardia during esmolol (P(ANOVA)=0.030) and esmolol
      inhibition of exercise-induced tachycardia [0.78+/-7.70, 5.11+/-4.05, 10.22+/
      9.78 bpm, respectively (P=0.014)]. The early effect of esmolol on exercise
      induced tachycardia was significantly greater among Arg389 than in Gly389
      homozygote healthy individuals (NCT01388036).

PMID- 23114280
TI  - Comparison of 2D melting criteria in a colloidal system.
AB  - We use super-paramagnetic spherical particles which are arranged in a two
      dimensional monolayer at a water/air interface to investigate the crystal to
      liquid phase transition. According to the KTHNY theory a crystal melts in thermal
      equilibrium by two continuous phase transitions into the isotropic liquid state
      with an intermediate phase, commonly known as the hexatic phase. We verify the
      significance of several criteria based on dynamical and structural properties to
      identify the crystal-hexatic and hexatic-isotropic liquid phase transitions for
      the same experimental data of the given setup. The criteria are the bond
      orientational correlation function, the Larson-Grier criterion, the 2D dynamic
      Lindemann parameter, the bond orientational susceptibility, the 2D Hansen-Verlet
      rule, the Lowen-Palberg-Simon criterion as well as a criterion based on the shape
      factor of Voronoi cells and Minkowski functionals. For our system with long-range
      repulsion, the bond order correlation function and bond order susceptibility work
      best to identify the hexatic-isotropic liquid transition and the 2D dynamic
      Lindemann parameter identifies unambiguously the hexatic-crystalline transition.

PMID- 23114281
TI  - Assisted reproductive technology surveillance--United States, 2009.
AB  - PROBLEM/CONDITION: Since the birth of the first U.S. infant conceived with
      Assisted Reproductive Technology (ART) in 1981, use of advanced technologies to
      overcome the problem of infertility has increased steadily, as has the number of
      fertility clinics providing ART services in the United States. ART includes
      fertility treatments in which both eggs and sperm are handled in the laboratory
      (i.e., in vitro fertilization [IVF] and related procedures). Women who undergo
      ART procedures are more likely to deliver multiple-birth infants than those who
      conceive naturally. Multiple births pose substantial risks to both mothers and
      infants, including pregnancy complications, preterm delivery, and low birthweight
      infants. This report presents the most recent data on ART use and birth outcomes
      for U.S. states and territories. REPORTING PERIOD COVERED: 2009. DESCRIPTION OF
      SYSTEM: In 1996, CDC began collecting data on all ART procedures performed in the
      United States, as mandated by the Fertility Clinic Success Rate and Certification
      Act of 1992 (FCSRCA) (Public Law 102-493 [October 24, 1992]). ART data for 1995
      2003 were obtained from the Society of Assisted Reproductive Technology (SART)
      through its proprietary Clinical Outcomes Reporting System data base (SART CORS).
      Since 2004, CDC has contracted with Westat, Inc., a statistical survey research
      organization, to obtain data from fertility clinics in the United States through
      the National ART Surveillance System (NASS), a web-based data collection system
      developed by CDC. RESULTS: In 2009, a total of 146,244 ART procedures were
      reported to CDC. These procedures resulted in 45,870 live-birth deliveries and
      60,190 infants. The largest numbers of ART procedures were performed among
      residents of California (18,405), New York (14,539), Illinois (10,192),
      Massachusetts (9,845), New Jersey (9,146), and Texas (8,244). Together, these six
      states reported the highest number of live-birth deliveries as a result of ART
      and accounted for 48% of all ART procedures initiated, 46% of all infants born
      from ART, and 45% of all ART multiple-birth deliveries but only 34% of all births
      in the United States. Nationally, the average number of ART procedures performed
      per 1 million women of reproductive age (15-44 years), which is a proxy indicator
      of ART utilization, was 2,361. In four states (Massachusetts, New York, New
      Jersey, and Connecticut) and the District of Columbia, this proxy measure of ART
      use exceeded twice the national average. Nationally, the average number of
      embryos transferred was 2.1 among women aged <35 years, 2.5 among women aged 35
      40 years, and 3.0 among women aged >40 years (and varied most in this age group
      from 1.7 in Maine to 3.5 in Missouri). Age-specific elective single-embryo
      transfer (eSET) rates were approximately 7% among women aged <35 years, 3% among
      women aged 35-40 years, and 0.5% among women aged >40 years. The highest rates of
      eSET were observed among women aged <35 years (41% in Delaware, 20% in Iowa, and
      17% Massachusetts). Overall, ART contributed to 1.4% of U.S. births (ranging from
      0.2% in Puerto Rico to 4.3 % in Massachusetts). The proportion of ART to total
      infants born in the state or territory, which is another measure of ART
      utilization, was highest in Massachusetts (>4%) with high rates also observed in
      New Jersey, New York, Connecticut, and the District of Columbia (>3% of all
      infants born). Infants conceived with ART accounted for 20% of all multiple-birth
      infants (ranging from 4% in Maine to 41% in New York), 19% of all twin births
      (ranging from 4% in Maine to 42% in New York) and 34% of triplet or higher order
      births (ranging from 0 in several states to 61.5% in New Jersey). Among infants
      conceived with ART, 47% were born as multiple-birth infants (ranging from 35% in
      Delaware to 60.8% in Wyoming), compared with only 3% of infants among the general
      birth population (ranging from 1% in New York to 5% in Connecticut). Nationally,
      infants conceived with ART contributed to approximately 6% of all low birthweight
      (<2,500 grams) infants, ranging from 1.3% in Mississippi to 15% in Massachusetts
      and to 6% of all very low birthweight (<1,500 grams) infants, ranging from 1% in
      Alaska to 15% in New Jersey. Overall, among ART-conceived infants, 32% were low
      birthweight (ranging from 20% in Alaska to 48% in Puerto Rico), compared with 8%
      among the general birth population (ranging from 5.8% in South Dakota to 12.2% in
      Mississippi), and 6% of ART infants were very low birthweight (ranging from 1.5%
      in Alaska to 13% in South Dakota), compared with 1% among the general birth
      population (ranging from 1% in Alaska to 2% in Mississippi and District of
      Columbia). Finally, ART-conceived infants accounted for 3.9% of all preterm (<37
      weeks; range: 0.5% in Puerto Rico to 11.1% in Massachusetts) and 4.5% of all very
      preterm births (<32 weeks; range: 0.5% in Puerto Rico to 12% in New York).
      Overall, among infants conceived with ART, 33.4% were born preterm (ranging from
      21.3% in Vermont to 47.1% in Wyoming), compared with 12.2% of the general birth
      population (ranging from 9.3% in Vermont to 18.0% in Mississippi), and 6.1% of
      ART infants were very preterm births (ranging from 1.5% in Alaska to 14.7% in
      South Dakota), compared with 2% among the general birth population (ranging from
      1.4% in Alaska, Oregon, Utah, and Washington to 3% in Mississippi).
      INTERPRETATION: The proportion of births from ART varied considerably by state
      and territory (ranging from 0.2% to 4.3%) with substantial impact on perinatal
      outcomes in some states. In most states, multiple births from ART accounted for
      substantial proportions of twins and triplets and higher order infants, and the
      rates of low birthweight and preterm births were disproportionately higher among
      ART infants than in the general birth population. More than one embryo was
      transferred per procedure in most states and territories for all age groups,
      influencing the overall multiple birth rates in the United States. ART use was
      represented disproportionately in the United States, with only 13 states having
      above-average ART use. High rates of ART utilization were observed in
      Massachusetts and New Jersey, which have comprehensive statewide-mandated health
      insurance coverage for ART procedures. Insurance mandates might influence ART
      utilization and ART-related birth outcomes. PUBLIC HEALTH ACTIONS: Promotion of
      single-embryo transfer, where feasible, is needed to reduce multiple births and
      related adverse consequences of ART. Nevertheless, because ART accounts for a
      relatively small fraction of total births in most states and territories, the
      overall prevalence of low birthweight and preterm births cannot be explained
      solely by the use of ART, and therefore non-ART causes of these adverse outcomes
      must be examined. Monitoring the use of non-ART infertility treatments (e.g.,
      ovulation stimulation medications without ART) in the general population might be
      useful because these treatments also might be associated with high rates of
      multiple births and adverse outcomes such as preterm delivery and infants born
      with low birthweight.

PMID- 23114282
TI  - Detection of local recurrent prostate cancer after radical prostatectomy in terms
      of salvage radiotherapy using dynamic contrast enhanced-MRI without endorectal
      coil.
AB  - PURPOSE: To evaluate the value of dynamic contrast enhanced Magnetic Resonance
      Imaging (DCE-MRI) without endorectal coil (EC) in the detection of local
      recurrent prostate cancer (PC) after radical prostatectomy (RP). MATERIAL AND
      METHODS: Thirty-three patients with recurrent PC underwent DCE-MRI without EC
      before salvage radiotherapy (RT). At median 15 (mean 16+/-4.9, range 12-27)
      months after completion of RT all patients showed complete biochemical response.
      Additional follow up post RT DCE-MRI scans were available. Prostate specific
      antigen (PSA) levels at the time of imaging were correlated to the imaging
      findings. RESULTS: In 22/33 patients (67%) early contrast enhancing nodules were
      detected in the post-prostatectomy fossa on pre-RT DCE-MRI images. The average
      pre-RT PSA level of the 22 patients with positive pre-RT DCE-MRI findings was
      significantly higher (mean, 0.74+/-0.64 ng/mL) compared to the pre-RT PSA level
      of the 11 patients with negative pre-RT DCE-MRI (mean, 0.24+/-0.13 ng/mL)
      (p<0.001). All post-RT DCE-MRI images showed complete resolution of initial
      suspicious lesions. A pre-RT PSA cut-off value of >=0.54 ng/ml readily predicted
      a positive DCE-MRI finding. CONCLUSIONS: This is the first study that shows that
      DCE-MRI without EC can detect local recurrent PC with an estimated accuracy of
      83% at low PSA levels. All false negative DCE-MRI scans were detected using a PSA
      cut-off of >=0.54 ng/mL.

PMID- 23114283
TI  - DropletMicroarray: facile formation of arrays of microdroplets and hydrogel
      micropads for cell screening applications.
AB  - We describe a one-step method for creating thousands of isolated pico- to
      microliter-sized droplets with defined geometry and volume. Arrays of droplets
      are instantly formed as liquid moves along a superhydrophilic-superhydrophobic
      patterned surface. Bioactive molecules, nonadherent cells, or microorganisms can
      be trapped in the fully isolated microdroplets for high-throughput screening, or
      in hydrogel micropads for screening in 3D microenvironments.

PMID- 23114284
TI  - Difficult clinical management of anti-tuberculosis DRESS syndrome.
AB  - We describe 11 cases of anti-tuberculosis DRESS (drug-related rash with
      eosinophilia and systemic symptoms) syndrome, a potentially serious complication
      of treatment that led to interruption of treatment for prolonged periods,
      systemic corticosteroid use and the resumption of treatment  with less effective
      regimens. All patients had rash and toxic hepatitis, one died of multi-organ
      failure and, contrary to expectations, the evolution of tuberculosis (advanced in
      most cases) did not progress under corticosteroid treatment. The drug most
      frequently involved was rifampicin,  while retreatment schemes included, in most
      cases, levofloxacin, ethambutol, streptomycin and cycloserine.

PMID- 23114286
TI  - Bilateral sequential trochleitis as the presenting feature of systemic lupus
      erythematosus.
AB  - A 26-year old woman presented with headache and pain in the left superonasal
      orbit, which worsened with vertical eye movements. She had no relevant medical
      history, and ophthalmologic evaluation was unremarkable. An orbital ultrasound
      showed enlargement of soft tissue in the region of the left trochlea consistent
      with trochleitis. Treatment with prednisone and multiple local injections of
      corticosteroids and analgesic nerve blocks failed to relieve her symptoms. The
      patient subsequently experienced right trochleitis, and 2 years after the onset
      of her initial symptoms, she developed systemic symptoms and signs that led to a
      diagnosis of systemic lupus erythematosus (SLE). Systemic immunosuppressive
      therapy was instituted, and the patient experienced marked relief in her
      ophthalmic symptoms. This case is unique in that not only bilateral sequential
      trochleitis was the presenting feature of SLE but also the ocular manifestations
      preceded the systemic manifestations of SLE by over 2 years.

PMID- 23114285
TI  - Post-hospitalization course and predictive signs of suicidal behavior of suicidal
      patients admitted to a psychiatric hospital: a 2-year prospective follow-up
      study.
AB  - BACKGROUND: Suicidal patients admitted to a psychiatric hospital are considered
      to be at risk of suicidal behavior (SB) and suicide. The present study aimed to
      seek predictors of SB recurrence of the high-risk patients by examining their
      post-hospitalization course. METHOD: The design was 2-year prospective follow-up
      study of patients consecutively admitted with SB to a psychiatric center in
      Tokyo. The DSM-IV diagnoses and SB-related features of subjects were determined
      in structured interviews. Subsequently, the subjects underwent a series of follow
      up assessments at 6-month intervals. The assessment included inquiries into SB
      recurrence, its accompanying suicidal intent (SI) and SF-8 health survey.
      Analyses of serial change over time in the follow-up data and Cox proportional
      hazards regression analyses of SB recurrence were performed. RESULTS: 106
      patients participated in this study. The dropout rate during the follow-up was
      9%. Within 2 years, incidences of SB as a whole, SB with certain SI (suicide
      attempt) and suicide were 67% (95% CI 58 - 75%), 38% (95% CI 29 - 47%) and 6%
      (95% CI 3 - 12%), respectively. Younger age, number of lifetime SBs and
      maltreatment in the developmental period were predictive of SB as a whole, and
      younger age and hopelessness prior to index admission were predictive of suicide
      attempt. Regarding diagnostic variables, anxiety disorders and personality
      disorders appeared to have predictive value for SB. Additionally, poor physical
      health assessed during the follow-up was indicated as a possible short-term
      predictor of SB recurrence. CONCLUSIONS: This study demonstrated a high incidence
      of SB and suicide and possible predictors of SB recurrence in the post
      hospitalization period of psychiatric suicidal patients. Specialized
      interventions should be developed to reduce the suicide risk of this patient
      population.

PMID- 23114287
TI  - Role of creatine phosphate as a myoprotective agent during coronary artery bypass
      graft in elderly patients.
AB  - OBJECTIVE: To evaluate the myocardial protective effect of exogenous creatine
      phosphate added to a cardioplegic solution for elderly patients undergoing a
      coronary artery bypass graft (CABG) in China. METHODS: Twenty-four patients
      (age>65 years) who underwent CABG were randomly divided into a control group
      (n=12) and an experimental group (n=12). The concentrations of malonyldehyde and
      superoxide dismutase in the blood were measured before aortic clamping and at 0,
      30, 60, and 120 min after the release of aortic clamping. Creatine phosphokinase
      (CK), creatine phosphokinase-MB (CK-MB), lactate dehydrogenase, and cardiac
      troponin T were measured before aortic clamping and at 2, 24, and 48 h after the
      release of aortic clamping. Myocardial ultrastructures were examined under an
      electron microscope. RESULTS: The concentrations of malonyldehyde in both groups
      increased after the release of aortic clamping (at 0, 30, 60, and 120 min), but
      were higher in the control group compared with the experimental group (P<0.01).
      The concentrations of superoxide dismutase in both groups were decreased after
      the release of aortic clamping and were higher in the experimental group compared
      with the control group (P<0.01) at 0, 30, 60, and 120 min after the release of
      aortic clamping. The values of CK, CK-MB, lactate dehydrogenase, and cardiac
      troponin T at 2, 24, and 48 h after the release of the aortic clamping were lower
      in the experimental group than in the control group (P<0.01). Electron microscopy
      showed that the mitochondria in the experimental group were histologically better
      than those in the control group. CONCLUSION: Exogenous creatine phosphate added
      to the cardioplegia solution can provide energy to myocardial cells and can
      relieve ischemia/reperfusion-related injury in elderly patients during CABG in
      China.

PMID- 23114290
TI  - Impact of charge variation on the encapsulation of nanoparticles by virus coat
      proteins.
AB  - Electrostatic interaction is the driving force for the encapsulation by virus
      coat proteins of nanoparticles such as quantum dots, gold particles and magnetic
      beads for, e.g., imaging and therapeutic purposes. In recent experimental work,
      Daniel et al (2010 ACS Nano 4 3853-60) found the encapsulation efficiency to
      sensitively depend on the interplay between the surface charge density of
      negatively charged gold nanoparticles and the number of positive charges on the
      RNA binding domains of the proteins. Surprisingly, these experiments reveal that
      despite the highly cooperative nature of the co-assembly at low pH, the
      efficiency of encapsulation is a gradual function of their surface charge
      density. We present a simple all-or-nothing mass action law combined with an
      electrostatic interaction model to explain the experiments. We find quantitative
      agreement with experimental observations, supporting the existence of a natural
      statistical charge distribution between nanoparticles.

PMID- 23114289
TI  - Risk assessment and decision making about  in-labour transfer from rural
      maternity care: a social judgment and signal detection analysis.
AB  - BACKGROUND: The importance of respecting women's wishes to give birth close to
      their local community is supported by policy in many developed countries.
      However, persistent concerns about the quality and safety of maternity care in
      rural communities have been expressed. Safe childbirth in rural communities
      depends on good risk assessment and decision making as to whether and when the
      transfer of a woman in labour to an obstetric led unit is required. This is a
      difficult decision. Wide variation in transfer rates between rural maternity
      units have been reported suggesting different decision making criteria may be
      involved; furthermore, rural midwives and family doctors report feeling isolated
      in making these decisions and that staff in urban centres do not understand the
      difficulties they face. In order to develop more evidence based decision making
      strategies greater understanding of the way in which maternity care providers
      currently make decisions is required. This study aimed to examine how midwives
      working in urban and rural settings and obstetricians make intrapartum transfer
      decisions, and describe sources of variation in decision making. METHODS: The
      study was conducted in three stages. 1. 20 midwives and four obstetricians
      described factors influencing transfer decisions. 2. Vignettes depicting an
      intrapartum scenario were developed based on stage one data. 3. Vignettes were
      presented to 122 midwives and 12 obstetricians who were asked to assess the level
      of risk in each case and decide whether to transfer or not. Social judgment
      analysis was used to identify the factors and factor weights used in assessment.
      Signal detection analysis was used to identify participants' ability to
      distinguish high and low risk cases and personal decision thresholds. RESULTS:
      When reviewing the same case information in vignettes midwives in different
      settings and obstetricians made very similar risk assessments. Despite this, a
      wide range of transfer decisions were still made, suggesting that the main source
      of variation in decision making and transfer rates is not in the assessment but
      the personal decision thresholds of clinicians. CONCLUSIONS: Currently health
      care practice focuses on supporting or improving decision making through skills
      training and clinical guidelines. However, these methods alone are unlikely to be
      effective in improving consistency of decision making.

PMID- 23114291
TI  - Work-related orthopaedic injury and feelings of depression: the potential role of
      physical therapy.

PMID- 23114292
TI  - Micro-macro discrepancies in nonlinear microrheology: II. Effect of probe shape.
AB  - In this second article devoted to 'computational experiments' of nonlinear
      microrheology, we examine the effect that changing the probe shape or motion has
      upon the three sources of discrepancy that we previously examined for spheres. In
      particular, prolate ellipsoidal probes have relatively long regions of relatively
      constant strain rate, giving predominantly shear and relative Lagrangian
      steadiness. The micro-macro discrepancy is shown not to arise from Lagrangian
      unsteadiness, but largely from the non-viscometric nature of the flows. Second,
      an oblate ellipsoidal probe exacerbates the extensional regions in front of and
      behind the probe. However, the relatively low extensional rates around such
      'disks' would require them to be pulled at much higher rates through the fluid in
      order to excite the extensional deformations. Because our model material thickens
      under uniaxial extension, but thins under biaxial extension, the contribution of
      each to the total drag is partially negated by the other. Finally, we examine a
      rotating spherical probe, which is Lagrangian steady and pure shear. We show that
      the apparent viscosity thus recovered is close to the true shear viscosity, and
      furthermore that the true shear viscosity can be extracted quantitatively from
      the apparent microviscosity.

PMID- 23114294
TI  - Compact grating couplers on silicon-on-insulator with reduced backreflection.
AB  - The backreflection in commonly used grating couplers on silicon-on-insulator
      (SOI) is not negligible for many applications. This reflection is dramatically
      reduced in our improved compact grating coupler design, which directs the
      reflection away from the input waveguide. Realized devices on SOI show that the
      reflection can be reduced down to -50 dB without an apparent transmission
      penalty.

PMID- 23114293
TI  - Percutaneous core needle biopsy versus open biopsy in diagnostics of bone and
      soft tissue sarcoma: a retrospective study.
AB  - BACKGROUND: Biopsy is a crucial step within the diagnostic cascade in patients
      with suspected bone or soft tissue sarcoma. Open biopsy is still considered the
      gold standard. However, recent literature suggests similar results for
      percutaneous biopsy techniques. Therefore, the aim of this retrospective analysis
      was to compare open and percutaneous core needle biopsy (CNB) regarding their
      accuracy in diagnosis of malignant musculoskeletal lesions. METHODS: From January
      2007 to December 2009, all patients with suspected malignant primary bone or soft
      tissue tumour undergoing a percutaneous CNB or open biopsy and a subsequent
      tumour resection at our department were identified and enrolled. Sensitivities,
      specificities, positive predictive values (PPV), negative predictive values (NPV)
      and diagnostic accuracy were calculated for both biopsy techniques and compared
      using Fisher's exact test. RESULTS: A total of 77 patients were identified and
      enrolled in this study. Sensitivity, specificity, PPV, NPV and diagnostic
      accuracy were 100% for CNB in bone tumours. Sensitivity (95.5%), NPV (91.7%) and
      diagnostic accuracy (93.3%) for open biopsy in bone tumours showed slightly
      inferior results without statistical significance (p > 0.05). In soft tissue
      tumours favourable results were obtained in open biopsies compared to CNB with
      differences regarding sensitivity (100% vs. 81.8%, p = 0.5), NPV (100% vs. 50%, p
      = 0.09) and diagnostic accuracy (100% vs. 84.6%, p = 0,19) without statistical
      significance. The overall diagnostic accuracy was 92.9% for CNB and 98.0% for
      open biopsy (p = 0.55). A specific diagnosis could be obtained in 84.2% and
      93.9%, respectively (p = 0.34). CONCLUSION: In our study we found moderately
      inferior results for the percutaneous biopsy technique compared to open biopsy in
      soft tissue tumours whereas almost equal results were obtained for both biopsy
      techniques for bone tumours. Thus, CNB is a safe, minimal invasive and cost
      effective technique for diagnosing bony lesions. In soft tissue masses, the
      indication for percutaneous core needle biopsy needs to be made carefully by an
      experienced orthopaedic oncologist with respect to the suspected entity, size of
      necrosis and location of the lesion to avoid incorrect or deficient results.

PMID- 23114295
TI  - Organic light-emitting-diode-based plasmonic dark-field microscopy.
AB  - We propose and demonstrate a compact, alignment-free dark-field microscopy
      technique, termed as organic light-emitting-diode-based plasmonic dark-field
      microscopy. Experimental results show that it is capable of forming dark-field
      images of the specimens utilizing a highly integrated chip-scale plasmonic
      condenser. This technique has high z resolution and high imaging contrast and is
      suitable for the dynamics study near the contact regions of living cells and the
      substrate.

PMID- 23114296
TI  - Generation of a phase-locked Raman frequency comb in gas-filled hollow-core
      photonic crystal fiber.
AB  - In a relatively simple setup consisting of a microchip laser as pump source and
      two hydrogen-filled hollow-core photonic crystal fibers, a broad, phase-locked,
      purely rotational frequency comb is generated. This is achieved by producing a
      clean first Stokes seed pulse in a narrowband guiding photonic bandgap fiber via
      stimulated Raman scattering and then driving the same Raman transition resonantly
      with a pump and Stokes fields in a second broadband guiding kagome-style fiber.
      Using a spectral interferometric technique based on sum frequency generation, we
      show that the comb components are phase locked.

PMID- 23114297
TI  - Simultaneous subchannel data updating for multiple channels of 16-quadrature
      amplitude modulation signals using a single periodically poled lithium niobate
      waveguide.
AB  - Subchannel data updating of high-order modulation format signals using cascaded
      sum- and difference-frequency generation in a single periodically poled lithium
      niobate waveguide is demonstrated. One quadrature phase-shift-keying subchannel
      of a 16-quadrature amplitude modulation (QAM) signal at 40 Gbit/s is successfully
      updated, with an optical signal-to-noise ratio (OSNR) penalty of ~2 dB for return
      to-zero and ~4 dB for non-return-to-zero at a bit-error rate (BER) of 2*10(-3).
      Simultaneous processing of four wavelength-multiplexed 16-QAM signals with an
      average OSNR penalty of 4.5 dB at a BER of 2*10(-3) is also demonstrated.

PMID- 23114298
TI  - Intrasweep phase-sensitive optical coherence tomography for noncontact optical
      photoacoustic imaging.
AB  - We introduce a method to extract the photoacoustic (PA) signal from the phase
      time evolution of an optical coherence tomography (OCT) swept source spectral
      sweep. This all-optical detection is achieved in a noncontact fashion directly on
      the sample surface by using its specular reflection. High-speed measurement and
      referencing allow for close to shot noise limited phase-sensitive detection. It
      offers a simple way to perform OCT and PA imaging by sharing the same system
      components.

PMID- 23114299
TI  - Kagome hollow-core photonic crystal fiber probe for Raman spectroscopy.
AB  - We demonstrate the use of a large-pitch Kagome-lattice hollow-core photonic
      crystal fiber probe for Raman spectroscopy. The large transmission bandwidth of
      the fiber enables both the excitation and Raman beams to be transmitted through
      the same fiber. As the excitation beam is mainly transmitted through air inside
      the hollow core, the silica luminescence background is reduced by over 2 orders
      of magnitude as compared to standard silica fiber probes, removing the need for
      fiber background subtraction.

PMID- 23114300
TI  - Generation of polarization-entangled photon pairs via concurrent spontaneous
      parametric downconversions in a single chi(2) nonlinear photonic crystal.
AB  - We propose a scheme for generating polarization-entangled photon pairs using a
      chi((2)) nonlinear photonic crystal, which is designed for enabling two
      concurrent quasi-phase-matched spontaneous parametric downconversion processes.
      Beamlike photon pairs produced from each process are collinear but noncollinear
      with the pump. Moreover, the source we design works in a postselection-free way
      and applies to both degenerate and nondegenerate cases. Combining possible
      waveguide technologies, our scheme may provide an integrated polarization
      entanglement source.

PMID- 23114301
TI  - Varifocal liquid lens based on microelectrofluidic technology.
AB  - This Letter presents a tunable liquid lens based on microelectrofluidic
      technology. In the microelectrofluidic lens (MEFL), electrowetting in the
      hydrophobic surface channel induces the Laplace pressure difference between two
      fluidic interfaces on the lens aperture and the surface channel. Then, the
      pressure difference makes the lens curvature tunable. In spite of the contact
      angle saturation, the narrow surface channel increases the Laplace pressure to
      have a wide range of optical power variation in the MEFL. The magnitude of the
      applied voltage determines the lens curvature in the analog mode MEFL. Digital
      operation is also possible when the control electrodes of the MEFL are patterned
      to have an array. The lens aperture and maximum surface channel diameter were
      designed to 3.2 mm and 6.4 mm, respectively, with a channel height of 0.2 mm for
      an optical power range between +210 and -30 D. By switching the control
      electrodes, the averaged transit time in steps and turnaround time were as low as
      2.4 ms and 16.5 ms, respectively, in good agreement with the simulation results.
      It is expected that the proposed MEFL may be widely used with advantages of wide
      variation of the optical power with fast and precise controllability in a digital
      manner.

PMID- 23114302
TI  - Self-assembled nanoparticle antiglare coatings.
AB  - Here we report a simple and scalable bottom-up technology for assembling close
      packed nanoparticle monolayers on both sides of a glass substrate as high-quality
      antiglare coatings. Optical measurements show that monolayer coatings consisting
      of 110 nm silica nanoparticles can significantly reduce optical reflectance and
      enhance specular transmittance of the glass substrate for a broad range of
      visible wavelengths. Both experiments and numerical simulations reveal that the
      antiglare properties of the self-assembled colloidal monolayers are significantly
      affected by the size of the colloidal particles.

PMID- 23114303
TI  - General approach to splicing optical microfibers via polymer nanowires.
AB  - We demonstrate a general approach to splicing microfibers via polymer nanowires.
      Chloroform dissolved polystyrene nanowires are used to splice silica, tellurite
      glass, and semiconductor microfibers or nanowires, with splicing loss down to
      0.51 dB. Using spliced microfiber structures, we also demonstrate microfiber ring
      resonators and Mach-Zehnder interferometers with high robustness. The splicing
      technique demonstrated here promises high potentials for robust optical
      integration of microfibers or nanowires for functional circuits or devices.

PMID- 23114304
TI  - Enhancement of response of a bistable VCSEL to modulated orthogonal optical
      feedback by vibrational resonance.
AB  - It is experimentally demonstrated that the response of a bistable vertical-cavity
      surface-emitting laser at a selected polarization to the effect of the modulated
      optical feedback at the orthogonal polarization can be considerably enhanced by
      the additional periodic current modulation via vibrational resonance. It shows up
      as a nonmonotonic dependence of the response at the frequency of the modulated
      optical feedback as a function of the amplitude of the current modulation. In
      such conditions the laser response can be amplified more than 80 times for a weak
      optical feedback. At the optimal amplitude of the current modulation a complete
      synchronization of optical switchings between polarization states with modulated
      optical feedback is observed. The effect of asymmetry of a bistable quasi
      potential is also experimentally demonstrated.

PMID- 23114305
TI  - High-Q microresonators for mid-IR light sources and molecular sensors.
AB  - We propose and demonstrate a simple and reliable method for fabricating high
      quality whispering-gallery mode (WGM) optical microresonators in "mid-IR
      relevant" low-loss ZrF(4)-BaF(2)-LaF(3)-AlF(3)-NaF (ZBLAN) glasses. Intrinsic
      quality factors of 10(7) have been demonstrated, providing great promise for WGM
      based mid-IR (MIR) devices. Absorption-limited Q-factors of over 3*10(8) are
      anticipated over the 2.0 to 3.2 MUm MIR wavelength range in ZBLAN microcavities
      in the foreseeable future.

PMID- 23114306
TI  - Visualizing the conoscopic isochromatic interference fringes in anisotropic
      crystals by spinning polarizer and analyzer.
AB  - In conventional conoscopic interference patterns of optically anisotropic
      materials the isochromatic interference fringes are inherently masked by the dark
      isogyres. We prove that the isochromatic fringes can be directly visualized by
      spinning the crossed linear polarizer and analyzer, regardless of the
      polarization state of the incident light. This simple method completely
      eliminates the isogyres and reveals the whole isochromatic fringes without the
      need of any additional optical elements or calculations. The system works at any
      wavelength that the linear polarizer permits. The validity of this method is
      demonstrated by observing the interference patterns of an LiNbO(3) electro-optic
      crystal under different external electric fields.

PMID- 23114307
TI  - Calibration of a thermal detector for pulse energy measurement of terahertz
      radiation.
AB  - We present a calibration method for measuring the terahertz pulse energy through
      a conventional thermal power detector. Short terahertz pulses were generated by
      mechanically modulating a continuous wave source with a chopper containing a
      narrow slot and detected by a Golay cell. We use a calibrated calorimeter to
      monitor the total source power so we can know the terahertz pulse energy in
      advance. The Golay detector response to rectangular pulses is theoretically
      analyzed and the peak amplitude of its output signal is found to be the relevant
      parameter to determine the pulse energy. We accomplish absolute calibration for
      the pulse responsivity of the Golay cell by examining the linear correlation
      between the output signal and the incident energy.

PMID- 23114308
TI  - Optical surface edge Bloch modes: low-loss subwavelength-scale two-dimensional
      light localization.
AB  - An optical surface edge Bloch mode is an optical state evanescently bound at an
      edge on a finite-size three-dimensional photonic crystal; the edge is the
      intersection of two termination planes on the crystal. Low-loss subwavelength
      scale edge modes can appear on an <010> edge of a dielectric woodpile within a
      complete photonic bandgap. The mode area is as small as 0.066 squared half-in
      vacuum-wavelengths. The edge mode has field maxima in vacuum near the termination
      surface, like surface plasmon modes. This edge mode would provide new
      opportunities of low-loss light localization in a sub-diffraction-limit space
      without the use of metal.

PMID- 23114309
TI  - Dispersion-free pulse duration reduction of passively Q-switched microchip
      lasers.
AB  - We present a dispersion-free method for the pulse duration reduction of passively
      Q-switched microchip laser (MCL) seed sources. This technique comprises two
      stages: one that carries out the self-phase modulation induced spectral
      broadening in a waveguide structure and a subsequent spectral filtering stage in
      order to shorten the pulses in time domain. The setup of a proof-of-principle
      experiment consists of a fiber-amplified passively Q-switched MCL, a passive
      single-mode fiber used as nonlinear element in which the spectrum is broadened,
      and a reflective volume-Bragg-grating acting as bandpass filter. A reduction of
      the pulse duration from 118 to 32 ps with high temporal quality has been achieved
      with this setup.

PMID- 23114310
TI  - Direct fabrication of seamless roller molds with gapless and shaped-controlled
      concave microlens arrays.
AB  - This Letter demonstrates the direct fabrication of gapless concave microlenses on
      glass cylinders, which can be used as seamless roller molds for the continuous
      imprinting of large-area microlens arrays. The method involves femtosecond laser
      exposures followed by a chemical wet-etching process. A honeycomb-like concave
      microlens array was fabricated on a glass cylinder with a diameter of 3 mm. We
      demonstrated the flexibility of the method in tuning the shape and depth of the
      concave structures by the arrangements of the laser exposure spots and laser
      powers, and examined the replicating ability of the roller mold by the polymer
      castling method.

PMID- 23114311
TI  - Sub 25 fs pulses from solid-core nonlinear compression stage at 250 W of average
      power.
AB  - We report on a highpower femtosecond fiber chirped-pulse amplification system
      with an excellent beam quality (M(2)=1.2) operating at 250 MHz repetition rate.
      We demonstrate nonlinear compression in a solid-core photonic crystal fiber at
      unprecedented average power levels. By exploiting self-phase modulation with
      subsequent chirped-mirror compression we achieve pulse shortening by more than
      one order of magnitude to 23 fs pulses. The use of circular polarization allows
      higher than usual peak powers in the broadening fiber resulting in compressed 0.9
      MUJ pulse energy and a peak power of 34 MW at 250 W of average power (M(2)=1.3).
      This system is well suited for driving cavity-enhanced high-repetition rate high
      harmonic generation.

PMID- 23114312
TI  - Intermodal Cerenkov radiation in a higher-order-mode fiber.
AB  - We demonstrate an intermodal Cerenkov radiation effect in a higher-order-mode
      (HOM) fiber with a mode crossing (i.e., two guided modes having the same
      propagation constant at the same wavelength). A frequency-shifted soliton in the
      vicinity of the mode-crossing wavelength emits a phase-matched dispersive wave in
      a different propagation mode. We develop a theoretical explanation for this
      nonlinear optical effect and demonstrate that the mode crossing in HOM fibers can
      be utilized to achieve simultaneous wavelength and mode conversion; the strength
      of this intermodal nonlinear interaction can be tuned by controlled fiber
      bending.

PMID- 23114313
TI  - Spatial heterodyne interferometry with polarization gratings.
AB  - The implementation of a polarization-based spatial heterodyne interferometer
      (SHI) is described. While a conventional SHI uses a Michelson interferometer and
      diffraction gratings, our SHI exploits mechanically robust Wollaston prisms and
      polarization gratings. A theoretical model for the polarization SHI is provided
      and validated with data from our proof of concept experiments. This device is
      expected to provide a compact monolithic sensor for subangstrom resolution
      spectroscopy in remote sensing, biomedical imaging, and machine vision
      applications.

PMID- 23114314
TI  - Diode-pumped femtosecond solid-state waveguide laser with a 4.9 GHz pulse
      repetition rate.
AB  - We report on the first demonstration of a passively mode-locked, diode-pumped,
      monolithic Yb:glass channel waveguide laser that incorporates a semiconductor
      saturable absorber mirror. Stable and self-starting mode-locking is achieved in a
      Fabry-Perot cavity configuration producing a pulse repetition rate up to 4.9 GHz.
      The shortest pulse duration of 740 fs is generated with 30 mW of average output
      power at a center wavelength of 1058 nm. A maximum output power of 81 mW is
      produced during mode-locking with corresponding pulse duration of 800 fs.

PMID- 23114315
TI  - Negative refraction and spatial echo in optical waveguide arrays.
AB  - The special symmetry properties of the discrete nonlinear Schrodinger equation
      allow a complete revival of the initial wave function employed in the context of
      stationary propagation of light in a waveguide array. As an inverting system, we
      propose a short array of almost isolated waveguides, which cause a relative pi
      phase shift in the neighboring waveguides. By means of numerical simulations of
      the model equations, we demonstrate what we believe is a novel mechanism for the
      negative refraction of spatial solitons.

PMID- 23114316
TI  - Broadly tunable mid-infrared noise-immune cavity-enhanced optical heterodyne
      molecular spectrometer.
AB  - The sensitive spectroscopic technique noise-immune cavity-enhanced optical
      heterodyne molecular spectroscopy (NICE-OHMS) has been successfully used in a
      variety of systems; however, no broadly tunable setup has been developed for the
      mid-infrared. To this end, we have integrated a difference frequency generation
      system into a NICE-OHMS setup. Initial optimization and characterization was
      completed with ro-vibrational spectroscopy of methane. Doppler-broadened
      frequency-modulated NICE-OHMS spectra were recorded at a sensitivity of 2*10(-7)
      cm(-1) Hz(-1/2). Sub-Doppler saturation signals (Lamb dips) were also observed
      using wavelength-modulated NICE-OHMS, achieving a sensitivity of ~6*10(-9) cm(-1)
      Hz(-1/2).

PMID- 23114317
TI  - High average brightness water window source for short-exposure cryomicroscopy.
AB  - Laboratory water window cryomicroscopy has recently demonstrated similar image
      quality as synchrotron-based microscopy but still with much longer exposure
      times, prohibiting the spread to a wider scientific community. Here we
      demonstrate high-resolution laboratory water window imaging of cryofrozen cells
      with 10 s range exposure times. The major improvement is the operation of a
      lambda=2.48 nm, 2 kHz liquid nitrogen jet laser plasma source with high spatial
      and temporal stability at high average brightness >1.5*10(12)
      ph/(s*sr*MUm(2)*line), i.e., close to that of early synchrotrons. Thus, this
      source enables not only biological x-ray microscopy in the home laboratory but
      potentially other applications previously only accessible at synchrotron
      facilities.

PMID- 23114318
TI  - Effect of the carrier-envelope-offset dynamics on the stabilization of a diode
      pumped solid-state frequency comb.
AB  - We investigate the dynamics of the carrier-envelope-offset (CEO) frequency,
      f(CEO), controlled by a pump current on the self-referencing of an optical
      frequency comb generated from a diode-pumped solid-state laser at 1.56 MUm. We
      observe a reversal point in the tuning of f(CEO) with the pump current. Between
      the low- and high-frequency region in the dynamic response of f(CEO) to pump
      current modulation, we observe a significant phase shift of ~180 deg in the
      transfer function. As a result, it is impossible to stabilize f(CEO) at a pump
      current above the reversal point, although the free-running CEO beat at this
      point has a higher signal-to-noise ratio than underneath the reversal point at
      which the locking is straightforward. Our results indicate that a high signal-to
      noise ratio and a low-noise CEO beat are not sufficient indicators for the
      feasibility of comb self-referencing in cases for which CEO dynamics play a
      dominant role.

PMID- 23114319
TI  - Super spontaneous four-wave mixing in single-channel side-coupled integrated
      spaced sequence of resonator structures.
AB  - We consider spontaneous four-wave mixing (SFWM) in a single-channel side-coupled
      integrated spaced sequence of resonators within a fully quantum formalism. We
      show that the probability of photon pair production can scale quadratically with
      the number of resonators, a phenomenon we call super SFWM, in analogy with super
      radiant spontaneous emission. Remarkably, in this situation the spectral
      probability density of the generated photons is independent of the number of
      rings.

PMID- 23114320
TI  - Hybrid Raman/fiber Bragg grating sensor for distributed temperature and discrete
      dynamic strain measurements.
AB  - We propose and experimentally demonstrate a hybrid fiber optic sensing technique
      that effectively combines Raman optical time domain reflectometry and in-line
      time-division-multiplexing for fiber Bragg grating (FBG) dynamic interrogation.
      The highly integrated proposed scheme employs broadband apodized low reflectivity
      FBGs with a single narrowband optical source and a shared receiver block,
      allowing for simultaneous measurements of distributed static temperature and
      discrete dynamic strain, over the same sensing fiber.

PMID- 23114321
TI  - Ultraviolet to near-infrared downconversion of Y2SiO5: Ce3+, Yb3+ nanobelt-poly
      EVA films.
AB  - The 1D Y(2)SiO(5): Ce(3+), Yb(3+) nanobelt phosphors and nanobelts-poly-ethylene
      vinyl acetate (poly-EVA) composite films were fabricated to explore spectral
      conversion materials for improving the conversion efficiency of c-Si solar cell.
      Scanning electron microscope, x-ray diffraction, photoluminescence excitation,
      photoluminescence (PL), transmission and decay curves were employed to
      characterize the structure, morphology, and optical properties. The nanobelt
      phosphor exhibits efficient ultraviolet (UV) absorption and gives intense near
      infrared (NIR) emission. The UV to NIR downconversion process in Y(2)SiO(5):
      Ce(3+), Yb(3+) nanobelts was investigated. More importantly, the thickness,
      transmission and PL spectra of nanobelts-poly-EVA films were also studied in
      detail. The NIR-emitting one-dimensional nanobelt-composite film may be applied
      as a promising spectral conversion layer for c-Si solar cell.

PMID- 23114322
TI  - Frequency-stabilized 1 W optical comb at 2.2-2.6 MUm by Cr2+:ZnSe multipass
      amplification.
AB  - We present a frequency comb source with power level up to 150 MUW per comb mode,
      tunable in the 2.2-2.6 MUm wavelength region, based on a Cr(2+):ZnSe multipass
      solid-state amplifier seeded by the output of an actively stabilized optical
      parametric oscillator, synchronously pumped by a commercial 250 MHz Er:fiber
      laser. Phase relationship between idler, signal, and pump waves is exploited to
      perform frequency comb stabilization in the whole 2.2-2.6 MUm mid-infrared
      spectral region.

PMID- 23114323
TI  - Imaging a full set of optical scattering properties of biological tissue by
      inverse spectroscopic optical coherence tomography.
AB  - We here develop a method to measure and image the full optical scattering
      properties by inverse spectroscopic optical coherence tomography (ISOCT). Tissue
      is modelled as a medium with continuous refractive index (RI) fluctuation and
      such a fluctuation is described by the RI correlation functions. Under the first
      order Born approximation, the forward model is established for ISOCT. By
      measuring optical quantities of tissue including the scattering power of the OCT
      spectrum, the reflection albedo alpha defined as the ratio of scattering
      coefficient MU(s), and the backscattering coefficient MU(b), we are able to
      inversely deduce the RI correlation function and image the full set of optical
      scattering properties.

PMID- 23114324
TI  - Surface-plasmon enhanced optical activity in two-dimensional metal chiral
      networks.
AB  - We investigated the optical properties of a novel chiral metamaterial; two
      dimensional metal chiral networks formed from metal ribbons deposited on a
      dielectric substrate. For zeroth-order transmitted light, sharp optical
      resonances were observed at spectral positions, which are determined by the
      surface plasmon resonance frequencies of the periodic metal structures. The
      experimental results are in excellent agreement with numerical calculations.

PMID- 23114325
TI  - Polymeric slot waveguide at visible wavelength.
AB  - Polymeric slot waveguide structure, which pushes the mode field toward the
      surrounding media, was designed and characterized. The slot waveguide was
      fabricated by using nanoimprint lithography, and the operation of the slot was
      demonstrated at 633 nm wavelength with an integrated Young interferometer. The
      experimental result shows that the nanolithography method provides possibilities
      to fabricate disposable slot waveguide sensors.

PMID- 23114326
TI  - Coherent perfect absorption mediated anomalous reflection and refraction.
AB  - We show bending of light on the same side of the normal in a free-standing
      corrugated metal film under bidirectional illumination. Coherent perfect
      absorption (CPA) is exploited to suppress the specular zeroth order leading to
      effective back-bending of light into the "-1" order, while the "+1" order is
      resonant with the surface mode. The effect is shown to be phase sensitive,
      yielding CPA and superscattering in the same geometry.

PMID- 23114327
TI  - Anderson localization of light in PT-symmetric optical lattices.
AB  - Anderson localization (AL) of light is investigated numerically in a disordered
      parity-time (PT)-symmetric potential, in the form of an optical lattice. The
      lattice is recorded in a nonlinear medium with Kerr nonlinearity. We demonstrate
      enhancement of light localization in a PT-symmetric lattice, as compared to the
      localization in the corresponding real lattice. The effect of strength of the
      gain-loss component in the PT lattice on various regimes of AL is also discussed.
      It is found that the localization exists and is further enhanced above the
      threshold strength of the imaginary part of the potential. The influence of
      nonlinearity and disorder level on the transverse localization of light in such a
      complex-valued potential is addressed.

PMID- 23114328
TI  - Beneficial use of spectral broadening resulting from the nonlinearity of the
      fiber-optic channel.
AB  - We discuss the possibility of exploiting spectral broadening resulting from fiber
      nonlinearity for the transmission of information. The spectral broadening induced
      by nonlinearity combined with the appropriate waveform can turn quadrature
      amplitude modulation-like constellations into frequency-shift-keying
      constellations over a much larger dimension. Thus, the Kerr effect can be thought
      of as a large dimensional mapper/modulator. A simple single-span fiber-optic link
      implemented over dispersion shifted fiber is assumed for the demonstration of the
      principle. It is shown that for a particular constellation the achievable data
      rates in the presence of nonlinearity can be significantly higher than the
      capacity characterizing a linear channel with the same input bandwidth.

PMID- 23114329
TI  - Part-per-trillion level SF6 detection using a quartz enhanced photoacoustic
      spectroscopy-based sensor with single-mode fiber-coupled quantum cascade laser
      excitation.
AB  - A sensitive spectroscopic sensor based on a hollow-core fiber-coupled quantum
      cascade laser (QCL) emitting at 10.54 MUm and quartz enhanced photoacoustic
      spectroscopy (QEPAS) technique is reported. The design and realization of mid-IR
      fiber and coupler optics has ensured single-mode QCL beam delivery to the QEPAS
      sensor. The collimation optics was designed to produce a laser beam of
      significantly reduced beam size and waist so as to prevent illumination of the
      quartz tuning fork and microresonator tubes. SF(6) was selected as the target
      gas. A minimum detection sensitivity of 50 parts per trillion in 1 s was achieved
      with a QCL power of 18 mW, corresponding to a normalized noise-equivalent
      absorption of 2.7*10(-10) W.cm(-1)/Hz(1/2).

PMID- 23114330
TI  - Grating-based at-wavelength metrology of hard x-ray reflective optics.
AB  - A mean of characterizing the tangential shape of a hard x-ray mirror is
      presented. Derived from a group of methods operating under visible light, its
      application in the x-ray domain using an x-ray absorption grating allows recovery
      of the mirror shape with nanometer accuracy and submillimeter spatial resolution.
      The method works with incoherent light, does not require any a priori information
      about the mirror characteristics and allows shape reconstruction of x-ray
      reflective optics under thermal and mechanical working conditions.

PMID- 23114331
TI  - Optofluidic magnetometer developed in a microstructured optical fiber.
AB  - A directional, in-fiber optofluidic magnetometer based on a microstructured
      optical fiber (MOF) Bragg-grating infiltrated with a ferrofluidic defect is
      presented. Upon application of a magnetic field, the ferrofluidic defect moves
      along the length of the MOF Bragg grating, modifying its reflection spectrum. The
      magnetometer is capable of measuring magnetic fields from 317 to 2500 G. The
      operational principle of such in-fiber magnetic field probe allows the
      elaboration of directional measurements of the magnetic field flux.

PMID- 23114333
TI  - Low-loss directional cloaks without superluminal velocity or magnetic response.
AB  - The possibility of making an optically large (many wavelengths in diameter)
      object appear invisible has been a subject of many recent studies. Exact
      invisibility scenarios for large (relative to the wavelength) objects involve
      (meta)materials with superluminal phase velocity [refractive index (RI) less than
      unity] and/or magnetic response. We introduce a new approximation applicable to
      certain device geometries in the eikonal limit: piecewise-uniform scaling of the
      RI. This transformation preserves the ray trajectories but leads to a uniform
      phase delay. We show how to take advantage of phase delays to achieve a limited
      (directional and wavelength-dependent) form of invisibility that does not require
      loss-ridden (meta)materials with superluminal phase velocities.

PMID- 23114334
TI  - Optically absorbing nanoparticle mediated cell membrane permeabilization.
AB  - Membrane permeabilization is imperative for gene and drug delivery systems, along
      with other cell manipulation methods, since the average eukaryotic cell membrane
      is not permeable to polar and large nonpolar molecules. Antibody conjugated
      optically absorbing gold nanospheres are targeted to the cell membrane of T47D
      breast cancer cell line and irradiated with 5 ns pulse, 20 Hz, 532 nm light to
      increase membrane permeability. Up to 90% permeabilization with less than 6%
      death is reported at radiant exposures up to 10 times lower than those of other
      comparable studies.

PMID- 23114335
TI  - High-transmission excited-state Faraday anomalous dispersion optical filter edge
      filter based on a Halbach cylinder magnetic-field configuration.
AB  - We report on the realization of an excited-state Faraday anomalous dispersion
      optical filter (ESFADOF) edge filter based on the 5P(3/2)->8D(5/2) transition in
      rubidium. A maximum transmission of 81% has been achieved. This high transmission
      is only possible by utilizing a special configuration of magnetic fields taken
      from accelerator physics to provide a strong homogeneous magnetic field of
      approximately 6000 G across the vapor cell. The two resulting steep transmission
      edges are separated by more than 13 GHz, enabling its application in remote
      sensing.

PMID- 23114336
TI  - Fiber-optic bending vector sensor based on Mach-Zehnder interferometer exploiting
      lateral-offset and up-taper.
AB  - A simple, compact, and highly sensitive optical fiber directional bend sensor is
      presented. This device consists of a lateral-offset splicing joint and an up
      taper formed through excessive fusion splicing method. The lateral-offset
      splicing breaks the cylindrical symmetry of the fiber and defines a pair of
      directions along which the bending response of the Mach-Zehnder interferometer
      transmission spectrum is different and thus could be used for bending vector
      measurement. For a curvature range from -3 to 3 m(-1), the bending sensitivities
      at 1463.86 nm and 1548.41 nm reach 11.987 nm/m(-1) and 8.697 nm/m(-1),
      respectively.

PMID- 23114337
TI  - Tunable and wideband microwave photonic phase shifter based on a single-sideband
      polarization modulator and a polarizer.
AB  - A novel microwave photonic phase shifter based on a single-sideband (SSB)
      polarization modulator (PolM) and a polarizer is proposed and demonstrated. In
      the SSB-PolM, two SSB intensity-modulated signals with a phase difference of pi
      along two orthogonal polarization directions are generated. With the polarizer to
      combine the two signals, the phase of the optical microwave signal can be tuned
      from -180 to 180 deg by simply adjusting the polarization direction of the
      polarizer, whereas the amplitude keeps unchanged. An experiment is carried out. A
      full-range tunable phase shift in the frequency range of 11-43 GHz is achieved.
      The flat power response, power independent operation, and high stability of the
      proposed microwave photonic phase shifter is also confirmed.

PMID- 23114338
TI  - Single-shot pulse-contrast measurement based on high-order quasi-phase-matching
      cross-correlation.
AB  - We propose a novel single-shot pulse-contrast measurement approach based on high
      order quasi-phase-matching (QPM) cross correlation. It supports perfect contrast
      measurement with features of no artifacts, high resolution, and large temporal
      window. The prototype experiment based on the noncollinear third QPM with a beam
      crossing angle of 90 deg, using femtosecond Ti:sapphire laser pulses with a
      contrast of ~10(7), demonstrates an artifacts-free measurement with a temporal
      window of ~70 ps and a resolution of ~900 fs.

PMID- 23114339
TI  - Fiber inline Michelson interferometer fabricated by a femtosecond laser.
AB  - A fiber inline Michelson interferometer was fabricated by micromachining a step
      structure at the tip of a single-mode optical fiber using a femtosecond laser.
      The step structure splits the fiber core into two reflection paths and produces
      an interference signal. A fringe visibility of 18 dB was achieved. Temperature
      sensing up to 1000 degrees C was demonstrated using the fabricated assembly-free
      device.

PMID- 23114340
TI  - Uncertainty-managed phase-shifting digital holography.
AB  - Phase-shifting digital holography is a digital measurement technology of a
      complex optical field profile that uses focal plane array detectors without the
      loss of bandwidth. It has been known that the accuracy of phase-shifting digital
      holography is limited mainly by the phase tolerance of reference. In this Letter,
      it is revealed that the uncertainty in an expected signal is highly dependent on
      the phase of the signal itself, as well as the phase tolerance of the reference.
      Based on the uncertainty analysis, we propose a novel scheme of phase-shifting
      digital holography that exploits an uncertainty property to enhance the
      measurement accuracy even under significant reference phase tolerance.

PMID- 23114341
TI  - Assessing the tissue-imaging performance of confocal microscope architectures via
      Monte Carlo simulations.
AB  - Various confocal microscope architectures have been developed for in vivo tissue
      imaging, including single-axis confocal (SAC) and dual-axis confocal (DAC)
      configurations utilizing both point-scanning (PS) and line-scanning (LS)
      approaches. While it is known that these design variations lead to tradeoffs in
      imaging performance, a quantitative comparison of the imaging performance of
      these configurations in highly turbid media would be of value. Here, we perform
      Monte Carlo simulations to evaluate the optical-sectioning capability of these
      various confocal microscope architectures in reflectance mode. In particular, we
      investigate the axial and transverse responses of these configurations to
      reflective targets at various depths within a homogenous scattering medium. We
      find that the DAC-PS configuration results in superior rejection of multiply
      scattered background light compared to all other configurations, followed in
      performance by the SAC-PS, the DAC-LS, and then the SAC-LS. Line scanning with
      both the DAC and SAC configurations leads to photon crosstalk between pixels.
      However, at shallow depths, the axial and transverse resolution of all
      configurations is maintained in a homogeneous scattering medium.

PMID- 23114342
TI  - Raman-induced Kerr-effect dual-comb spectroscopy.
AB  - We report on the first (to our knowledge) demonstration of nonlinear dual
      frequency-comb spectroscopy. In multi-heterodyne femtosecond Raman-induced Kerr
      effect spectroscopy, the Raman gain resulting from the coherent excitation of
      molecular vibrations by a spectrally narrow pump is imprinted onto the
      femtosecond laser frequency comb probe spectrum. The birefringence signal induced
      by the nonlinear interaction of these beams and the sample is heterodyned against
      a frequency comb local oscillator with a repetition frequency slightly different
      from that of the comb probe. Such time-domain interference provides multiplex
      access to the phase and amplitude Raman spectra over a broad spectral bandwidth
      within a short measurement time.

PMID- 23114343
TI  - Secure passive optical network based on chaos synchronization.
AB  - A physical-enhanced secure passive optical network (PON) based on chaos
      synchronization is proposed and numerically demonstrated. In this scheme, the
      chaotic output of an external-cavity semiconductor laser is used as the
      transmission carrier in both downstream and upstream directions, the chaos
      modulation technology is used to encrypt the downstream data, and the multiplexed
      subcarrier-modulation technology is adopted for the upstream transmission.
      Simulation results demonstrate that both the downstream data and the upstream
      data encrypted into the chaotic carriers can be successfully decrypted; moreover,
      the security of downstream can be enhanced by properly increasing the bit rate,
      and the upstream security can be maintained at a high level. The proposed PON
      affords secure all-optical access at the physical layer.

PMID- 23114344
TI  - Faithful communication Hamiltonian in photonic lattices.
AB  - Faithful communication is a necessary precondition for large scale all-optical
      networking and quantum information processing. Related theoretical investigations
      in different areas of physics have led to various proposals in which finite
      discrete lattices are used as channels for short-distance communication tasks.
      Here, in the framework of femtosecond-laser-written waveguide arrays, we present
      the first experimental realization of such a channel with judiciously engineered
      couplings.

PMID- 23114345
TI  - Optical vortices induced in nonlinear multilevel atomic vapors.
AB  - In a numerical investigation, we demonstrate the existence and curious evolution
      of vortices in a ladder-type three-level nonlinear atomic vapor with linear,
      cubic, and quintic susceptibilities considered simultaneously with the dressing
      effect. We find that the number of beads and topological charge of the incident
      beam, as well as its size, greatly affect the formation and evolution of
      vortices. To determine the number of induced vortices and the corresponding
      rotation direction, we give common rules associated with the initial conditions
      coming from various incident beams.

PMID- 23114346
TI  - Prospective for creating a near-field scalpel for laser surgery.
AB  - The efficient electric field enhancement due to coating a dielectric wedge by
      plasmon-carrying nanowires has been demonstrated numerically within the framework
      of the finite-difference frequency-domain method. The numerical simulations show
      increasing of electric field intensity in the near-field region of the dielectric
      wedge coated by silver nanowires in the regime of local plasmon excitation up to
      100 times versus the uncoated case.

PMID- 23114347
TI  - CW-lasing and amplification in Tm(3+)-doped photonic crystal fiber rod.
AB  - We report lasing and amplification in a rod type thulium-doped photonic crystal
      fiber with 80 MUm core diameter. The rod is pumped with a 793 nm laser diode and
      produces more than 20 W output power at a beam quality M(2)<1.3. The
      laser/amplifier has a slope efficiency of 27.8%/20.1% relative to absorbed pump
      power with a lasing threshold at 28.6 W. The output wavelength in the lasing
      configuration can be tuned over 180 nm from 1810-1990 nm.

PMID- 23114348
TI  - Focusing dynamics on circular distributed tapered metallic waveguides by means of
      plasmonic vortex lenses.
AB  - We investigate the focusing effect on circularly distributed planar tapered
      plasmonic waveguides by means of three-dimensional (3D) finite elements
      simulations. The proposed configuration allows nanofocusing on four faced planar
      nanotips, showing efficient condensation of surface plasmons polaritons (SPPs) at
      the silver/air interface toward the endpoint of the tips. By means of a plasmonic
      vortex lens it is possible to illuminate the tips with SPP waves carrying orbital
      angular momentum (OAM), namely plasmonic vortices. Our 3D simulations show that
      by acting on the topological charge of the plasmonic vortex the electric field
      charge distribution at the tips apex can be controlled accordingly to the input
      electric field phase distribution. The results for three particular OAM values
      are shown, along with a generalization for arbitrary plasmonic vortex angular
      momentum values.

PMID- 23114349
TI  - Second-Stokes dual-wavelength operation at 1321 and 1325 nm ceramic Nd:YAG/BaWO4
      Raman laser.
AB  - A diode-pumped, actively Q-switched second-Stokes dual-wavelength laser employing
      ceramic Nd:YAG as the gain medium and BaWO(4) as the Raman medium is
      demonstrated. The dual-wavelength Raman laser emission at 1321 and 1325 nm is
      based on the dual-wavelength fundamental laser emission at 1061 and 1064 nm. With
      a pump power of 18.4 W and pulse repetition frequency of 15 kHz, a maximum dual
      wavelength output power of 1.67 W was obtained, comprising a 0.75 W, 1321 nm
      laser component and a 0.92 W, 1325 nm laser component. The corresponding dual
      wavelength second-Stokes pulse width was 2.9 ns.

PMID- 23114350
TI  - Soliton mode locking fiber laser with an all-fiber polarization interference
      filter.
AB  - An erbium doped fiber ring laser achieving soliton mode locking by the use of an
      intra-cavity all-fiber polarization interference filter (AFPIF) has been
      demonstrated. To incorporate an AFPIF with relative narrow transmission
      bandwidth, the laser has produced clean soliton pulses of 1.2 ps duration at a
      repetition rate of 14.98 MHz with a polarization extinction ratio up to 25.7 dB.
      Moreover, we have demonstrated that the operating wavelength of the mode locking
      laser can be tuned over 20 nm range from 1545 to 1565 nm by thermally tuning the
      AFPIF cavity.

PMID- 23114351
TI  - Narrow linewidth laterally coupled 1.55 MUm AlGaInAs/InP distributed feedback
      lasers integrated with a curved tapered semiconductor optical amplifier.
AB  - We present a laterally coupled 1.55 MUm AlGaInAs/InP distributed feedback laser
      monolithically integrated with a curved tapered optical amplifier, providing an
      output power of 210 mW with single transverse and longitudinal mode operation
      exhibiting a record low linewidth of 64 kHz.

PMID- 23114352
TI  - Dual-channel polarization holography: a technique for recording two complex
      amplitude components of a vector wave.
AB  - In this Letter, the principle of polarization holography for recording an
      arbitrary vector wave on a thin polarization-sensitive recording medium is
      proposed. It is analytically shown that the complex amplitudes of p- and s
      polarization components are simultaneously recorded and independently
      reconstructed by using an s-polarized reference beam. The characteristics are
      experimentally verified.

PMID- 23114353
TI  - Amplifier similariton fiber laser with nonlinear spectral compression.
AB  - We propose a new concept of a fiber laser architecture supporting self-similar
      pulse evolution in the amplifier and nonlinear spectral pulse compression in the
      passive fiber. The latter process allows for transform-limited picosecond pulse
      generation, and improves the laser's power efficiency by preventing strong
      spectral filtering from being highly dissipative. Aside from laser technology,
      the proposed scheme opens new possibilities for studying nonlinear dynamical
      processes. As an example, we demonstrate a clear period-doubling route to chaos
      in such a nonlinear laser system.

PMID- 23114354
TI  - Improved sinusoidal phase plate to extend depth of field in incoherent hybrid
      imaging systems.
AB  - An improved sinusoidal phase plate is proposed by adding a new parameter to the
      conventional sinusoidal phase plate. A series of performance comparisons are made
      among various phase plates, including sinusoidal, cubic phase, and the modified
      logarithmic phase. The results demonstrate that the improved sinusoidal phase
      plate can further extend the depth of field in incoherent hybrid imaging systems,
      with lower surface relief phase structures fabricated in photoresist (AR-N 4340,
      ALL Resist, Germany).

PMID- 23114355
TI  - Generating a sub-wavelength Bessel-like light beam using a tapered hollow tube.
AB  - We present a series of sub-wavelength annular aperture (SAA) structures with
      annular width equal to the tip of a tapered hollow tube, which was fabricated
      using a heat-pulled method. The light beams emitted from the SAA-like structures
      created by the tapered hollow tube produced light beams characteristic of Bessel
      beams. We obtained a sub-micrometer focal spot with a depth-of-focus larger than
      7 MUm and identified the proper structure parameters needed to generate Bessel
      like light beams. Our new design has potential application to areas such as
      optical lithography, optical trapping, and the fabrication of high aspect ratio
      structures.

PMID- 23114356
TI  - Soliton generation by counteracting gain-guiding and self-bending.
AB  - We introduce a concept for stable spatial soliton formation, mediated by the
      competition between self-bending induced by a strongly asymmetric nonlocal
      nonlinearity and spatially localized gain superimposed on a wide pedestal with
      linear losses. When acting separately both effects seriously prevent stable
      localization of light, but under suitable conditions they counteract each other,
      forming robust soliton states that are attractors for a wide range of material
      and input light conditions.

PMID- 23114357
TI  - Multipeaked gap solitons in PT-symmetric optical lattices.
AB  - We report the existence and stability properties of multipeaked solitons in a
      defocusing Kerr medium with an imprinted complex optical lattice featuring a
      parity-time (PT) symmetry. Various families of soliton solutions with a different
      number of peaks are found in the first finite gap of the lattice. Linear
      stability analysis corroborated by direct propagation simulations reveals that
      multipeaked gap solitons can propagate stably in a wide range, provided that
      their propagation constant exceeds a critical value. Our findings demonstrate,
      for the first time, the existence of stable multipeaked gap solitons in a PT
      symmetric lattice.

PMID- 23114358
TI  - High-power very large mode-area thulium-doped fiber laser.
AB  - Large-pitch photonic-crystal fibers have demonstrated their unique capability of
      combining very large mode areas, high output powers and robust single-mode
      operation at a wavelength of 1 MUm. In this Letter, we present the experimental
      realization of thulium-doped very large mode-area fibers based on the large-pitch
      fibers with record mode-field diameters exceeding 60 MUm and delivering more than
      52 W of output power.

PMID- 23114359
TI  - Raman lasing in a chalcogenide microwire-based Fabry-Perot cavity.
AB  - We propose and demonstrate an all-chalcogenide microwire Raman laser, the first
      to our knowledge. The gain medium is provided by the Raman effect in a
      chalcogenide microwire and two Fabry-Perot resonant media are tested for lasing:
      (1) a cavity made out of a Fresnel reflection at one end of the microwire and a
      silver coated, broadband mirror at the other end, and (2) a cavity made out of
      Fresnel reflections at both ends of the microwire. The microwires are pumped in
      the C-band, and the resulting Raman lasers operate in the L-band. Such an all
      chalcogenide microwire laser has the potential to operate over the entire
      transmission window of chalcogenide glasses, i.e., in the wavelength range of 1.5
      10 MUm.

PMID- 23114360
TI  - Study of the birth of a vortex at Fraunhofer zone.
AB  - We analytically and experimentally study the Fraunhofer diffraction of an optical
      vortex beam possessing noninteger values of the azimuthal index. We show that the
      Fraunhofer diffraction of this beam presents the birth of a vortex at
      alpha=n+epsilon, where n is an integer number and epsilon is a small fraction. We
      discuss this behavior on the basis of the born vortex movement from a position of
      low intensity to high intensity when alpha is increased of an integer number in
      fractional steps of epsilon.

PMID- 23114361
TI  - Ultralong-range phase imaging with orthogonal dispersive spectral-domain optical
      coherence tomography.
AB  - An orthogonal dispersive spectral-domain optical coherence tomography (SDOCT)
      system based on a spectrometer consisting of a high spectral resolution virtually
      imaged phased array (VIPA) and a low resolution diffraction grating is developed.
      Two-dimensional (2D) dispersion generated by the combination of the VIPA and the
      grating in conjunction with a 2D CCD leads to an improved performance of the
      spectrometer. Ultrahigh spectral resolution of 0.002 nm within a free spectrum
      range of 50 nm is realized, providing the spectrometer with a spectral sampling
      rate up to ~10(5). The developed SDOCT realizes an imaging depth over 80 mm,
      which is the longest depth range ever achieved by SDOCT. The increased spectral
      sampling rate also results in a high signal-to-noise ratio of the SDOCT system.
      The application of the developed system is further illustrated by quantitative
      phase imaging of a glass plate and an optical lens.

PMID- 23114362
TI  - Experimental measurement of the number of modes for a multimode optical fiber.
AB  - For a multimode optical fiber, the number of modes (N(m)) can be calculated by
      analytic theory when the fiber is straight, twist-free, and strain-free. In
      practice, however, the fiber is subject to distortions that modify its mode
      characteristics. In this Letter, we present an experimental method to interrogate
      the mode properties of a multimode optical fiber. We experimentally measured the
      transmission matrix of a multimode optical fiber and performed singular value
      decomposition. We proved, both theoretically and experimentally, that the rank of
      the transmission matrix is equal to N(m). We expect that the suggested method
      will contribute to the fields of the biomedical optics and optical communications
      where optical fiber is widely used.

PMID- 23114363
TI  - Degenerate 1 GHz repetition rate femtosecond optical parametric oscillator.
AB  - We report a degenerate femtosecond optical parametric oscillator (OPO) that is
      synchronously pumped by a mode-locked Ti:sapphire laser at 1 GHz repetition rate.
      The OPO produces an 85 nm (10 THz) wide frequency comb centered at 1.6 MUm.
      Stable long-term operation with >100 mW of average output power has been
      achieved.

PMID- 23114364
TI  - Submicrometer radius and highly confined plasmonic ring resonator filters based
      on hybrid metal-oxide-semiconductor waveguide.
AB  - We numerically report the submicrometer radius (0.5 MUm) and high confinement
      (mode area ~lambda(2)/1200) plasmonic ring resonators for both all-pass and add
      drop filters based on the hybrid metal-oxide-semiconductor (Ag-SiO(2)-Si)
      waveguide platform. The best tradeoff between the propagation length and the
      confinement of this hybrid plasmonic waveguide platform is also discussed and
      compared to the dielectric-loaded plasmonic waveguide counterpart. We show that
      the ring resonator all-pass filter features an extinction ratio as high as 23 dB
      with a transmission loss of 1.5 dB, and a wide free spectral range of 168 nm with
      a bandwidth of 14 nm. Moreover, the demonstrated add-drop filter achieves an
      extinction ratio larger than 12 dB with a channel isolation between the through
      and drop channels of 13.5 dB at the resonant wavelength. These demonstrated
      plasmonic devices reveal as potential building blocks for future nanoscale
      electronic-photonic integrated circuits.

PMID- 23114365
TI  - Effects of confinement and external fields on structure and transport in
      colloidal dispersions in reduced dimensionality.
AB  - In this work, we focus on low-dimensional colloidal model systems, via simulation
      studies and also some complementary experiments, in order to elucidate the
      interplay between phase behavior, geometric structures and transport properties.
      In particular, we try to investigate the (nonlinear!) response of these very soft
      colloidal systems to various perturbations: uniform and uniaxial pressure, laser
      fields, shear due to moving boundaries and randomly quenched disorder. We study
      ordering phenomena on surfaces or in monolayers by Monte Carlo computer
      simulations of binary hard-disk mixtures, the influence of a substrate being
      modeled by an external potential. Weak external fields allow a controlled tuning
      of the miscibility of the mixture. We discuss the laser induced de-mixing for the
      three different possible couplings to the external potential. The structural
      behavior of hard spheres interacting with repulsive screened Coulomb or dipolar
      interaction in 2D and 3D narrow constrictions is investigated using Brownian
      dynamics simulations. Due to misfits between multiples of the lattice parameter
      and the channel widths, a variety of ordered and disordered lattice structures
      have been observed. The resulting local lattice structures and defect
      probabilities are studied for various cross sections. The influence of a self
      organized order within the system is reflected in the velocity of the particles
      and their diffusive behavior. Additionally, in an experimental system of dipolar
      colloidal particles confined by gravity on a solid substrate we investigate the
      effect of pinning on the dynamics of a two-dimensional colloidal liquid. This
      work contains sections reviewing previous work by the authors as well as new,
      unpublished results. Among the latter are detailed studies of the phase
      boundaries of the de-mixing regime in binary systems in external light fields,
      configurations for shear induced effects at structured walls, studies on the
      effect of confinement on the structures and defect densities in three-dimensional
      systems, the effect of confinement and barriers on two-dimensional flow and
      diffusion, and the effect of pinning sites on the diffusion.

PMID- 23114366
TI  - Calibration transfer based on maximum margin criterion for qualitative analysis
      using Fourier transform infrared spectroscopy.
AB  - A traditional multivariate calibration transfer method such as piecewise direct
      standardization (PDS) is usually applied to quantitative analysis. To make the
      method apply to qualitative analysis of Fourier Transform Infrared spectroscopy
      (FTIR), we propose an improved calibration transfer method based on the maximum
      margin criterion (CTMMC). The new method not only considers the spectral changes
      under different conditions, but also takes into account the geometric
      characteristics of spectra from different classes, so the transformed spectra
      from different classes will be separated as far as possible, and this will
      improve the performance of the follow-up qualitative analysis. A comparative
      study is provided between the proposed method CTMMC and other traditional
      calibration transfer methods on two data sets. Experimental results show that the
      proposed method can achieve better performance than previous methods.

PMID- 23114367
TI  - Degeneration of serotonergic neurons in amyotrophic lateral sclerosis: a link to
      spasticity.
AB  - Spasticity is a common and disabling symptom observed in patients with central
      nervous system diseases, including amyotrophic lateral sclerosis, a disease
      affecting both upper and lower motor neurons. In amyotrophic lateral sclerosis,
      spasticity is traditionally thought to be the result of degeneration of the upper
      motor neurons in the cerebral cortex, although degeneration of other neuronal
      types, in particular serotonergic neurons, might also represent a cause of
      spasticity. We performed a pathology study in seven patients with amyotrophic
      lateral sclerosis and six control subjects and observed that central serotonergic
      neurons suffer from a degenerative process with prominent neuritic degeneration,
      and sometimes loss of cell bodies in patients with amyotrophic lateral sclerosis.
      Moreover, distal serotonergic projections to spinal cord motor neurons and
      hippocampus systematically degenerated in patients with amyotrophic lateral
      sclerosis. In SOD1 (G86R) mice, a transgenic model of amyotrophic lateral
      sclerosis, serotonin levels were decreased in brainstem and spinal cord before
      onset of motor symptoms. Furthermore, there was noticeable atrophy of serotonin
      neuronal cell bodies along with neuritic degeneration at disease onset. We
      hypothesized that degeneration of serotonergic neurons could underlie spasticity
      in amyotrophic lateral sclerosis and investigated this hypothesis in vivo using
      tail muscle spastic-like contractions in response to mechanical stimulation as a
      measure of spasticity. In SOD1 (G86R) mice, tail muscle spastic-like contractions
      were observed at end-stage. Importantly, they were abolished by 5
      hydroxytryptamine-2b/c receptors inverse agonists. In line with this, 5
      hydroxytryptamine-2b receptor expression was strongly increased at disease onset.
      In all, we show that serotonergic neurons degenerate during amyotrophic lateral
      sclerosis, and that this might underlie spasticity in mice. Further research is
      needed to determine whether inverse agonists of 5-hydroxytryptamine-2b/c
      receptors could be of interest in treating spasticity in patients with
      amyotrophic lateral sclerosis.

PMID- 23114368
TI  - Distinct roles of dopamine and subthalamic nucleus in learning and probabilistic
      decision making.
AB  - Even simple behaviour requires us to make decisions based on combining multiple
      pieces of learned and new information. Making such decisions requires both
      learning the optimal response to each given stimulus as well as combining
      probabilistic information from multiple stimuli before selecting a response.
      Computational theories of decision making predict that learning individual
      stimulus-response associations and rapid combination of information from multiple
      stimuli are dependent on different components of basal ganglia circuitry. In
      particular, learning and retention of memory, required for optimal response
      choice, are significantly reliant on dopamine, whereas integrating information
      probabilistically is critically dependent upon functioning of the glutamatergic
      subthalamic nucleus (computing the 'normalization term' in Bayes' theorem). Here,
      we test these theories by investigating 22 patients with Parkinson's disease
      either treated with deep brain stimulation to the subthalamic nucleus and
      dopaminergic therapy or managed with dopaminergic therapy alone. We use
      computerized tasks that probe three cognitive functions-information acquisition
      (learning), memory over a delay and information integration when multiple pieces
      of sequentially presented information have to be combined. Patients performed the
      tasks ON or OFF deep brain stimulation and/or ON or OFF dopaminergic therapy.
      Consistent with the computational theories, we show that stopping dopaminergic
      therapy impairs memory for probabilistic information over a delay, whereas deep
      brain stimulation to the region of the subthalamic nucleus disrupts decision
      making when multiple pieces of acquired information must be combined.
      Furthermore, we found that when participants needed to update their decision on
      the basis of the last piece of information presented in the decision-making task,
      patients with deep brain stimulation of the subthalamic nucleus region did not
      slow down appropriately to revise their plan, a pattern of behaviour that mirrors
      the impulsivity described clinically in some patients with subthalamic nucleus
      deep brain stimulation. Thus, we demonstrate distinct mechanisms for two
      important facets of human decision making: first, a role for dopamine in memory
      consolidation, and second, the critical importance of the subthalamic nucleus in
      successful decision making when multiple pieces of information must be combined.

PMID- 23114369
TI  - A randomized, controlled, phase 1/2 trial of a Neisseria meningitidis serogroup B
      bivalent rLP2086 vaccine in healthy children and adolescents.
AB  - BACKGROUND: Neisseria meningitidis serogroup B (MnB) is a significant cause of
      invasive meningococcal disease. Factor H binding protein (also known as LP2086)
      is a conserved outer membrane neisserial lipoprotein that has emerged as a strong
      candidate protein antigen for MnB vaccination. This study examined the safety,
      tolerability and immunogenicity of an initial formulation of a bivalent
      recombinant LP2086 (rLP2086) vaccine in healthy children and adolescents.
      METHODS: In this randomized, observer-blinded, parallel-group, multicenter trial
      conducted at 6 centers in Australia, 127 healthy participants aged 8-14 years
      were assigned to receive 20, 60 or 200 ug of the bivalent rLP2086 vaccine (n =
      16, 45 and 45, respectively) or active control (Twinrix, n = 21) at 0, 1 and 6
      months. Immunogenicity was assessed before the first dose and 1 month after doses
      2 and 3. Local reactions, systemic events and other adverse events were recorded.
      The primary immunogenicity endpoint was the rate of seroconversion (>=4-fold rise
      in human complement serum bactericidal assay titer) against MnB strains
      expressing the homologous A05 or heterologous B02 LP2086 variants. RESULTS: The
      bivalent rLP2086 vaccine was generally well-tolerated, with mostly mild to
      moderate local reactions. The most common adverse events, headache and upper
      respiratory tract infection, occurred with similar frequency in each group. Post
      dose 3 seroconversion rates against strains expressing B02 and A05 variants were
      68.8-95.3% for rLP2086 recipients and 0% for Twinrix recipients. CONCLUSIONS: The
      bivalent rLP2086 vaccine was well-tolerated and immunogenic in healthy children
      and adolescents, supporting further evaluation as a broadly protective MnB
      vaccine.

PMID- 23114370
TI  - Corticosteroid therapy in genotype ST-11 meningococcal infections.
AB  - Corticosteroid treatment for meningococcal disease is debated. We report a high
      risk of death (odds ratio 4.68, 95% confidence interval: 1.91-11.46; P = 0.001)
      without corticosteroid treatment when meningococcal disease is provoked by
      isolates belonging to the hyperinvasive genotype ST-11. Genotypes of
      meningococcal isolates should be considered with corticosteroids therapy for
      meningococcal disease.

PMID- 23114371
TI  - Role of biofilm formation in Ureaplasma antibiotic susceptibility and development
      of bronchopulmonary dysplasia in preterm neonates.
AB  - BACKGROUND: Ureaplasma respiratory tract colonization is a risk factor for
      bronchopulmonary dysplasia (BPD) in preterm infants, but whether Ureaplasma
      isolates from colonized infants can form biofilms is unknown. We hypothesized
      that Ureaplasma isolates vary in capacity to form biofilms that contribute to
      their antibiotic resistance and ability to evade host immune responses. Study
      objectives were to (1) determine the ability of Ureaplasma isolates from preterm
      neonates to form biofilms in vitro; (2) compare the susceptibility of the sessile
      and planktonic organisms to azithromycin (AZI) and erythromycin; and (3)
      determine the relationship of biofilm-forming capacity in Ureaplasma isolates and
      the risk for BPD. METHODS: Forty-three clinical isolates from preterm neonates
      and 5 American Tissue Culture Collection strains were characterized for their
      capacity to form biofilms in vitro, and antibiotic susceptibility was performed
      on each isolate prebiofilm and postbiofilm formation. RESULTS: Forty-one (95%)
      clinical and 4 of 5 (80%) American Tissue Culture Collection isolates formed
      biofilms. All isolates were more susceptible to AZI (minimum inhibitory
      concentration, MIC50 2 ug/mL) than erythromycin (MIC50 4 ug/mL), and biofilm
      formation did not significantly affect antibiotic susceptibility for the 2 tested
      antibiotics. The MIC50 and minimum biofilm inhibitory concentrations (MBIC50) for
      Ureaplasma urealyticum clinical isolates for AZI were higher than for MIC50 and
      MBIC50 for Ureaplasma parvum isolates. There were no differences in MIC or MBICs
      among isolates from BPD infants and non-BPD infants. CONCLUSIONS: Capacity to
      form biofilms is common among Ureaplasma spp. isolates, but biofilm formation did
      not impact MICs for AZI or erythromycin.

PMID- 23114372
TI  - Antibody persistence and response to a booster dose of a quadrivalent conjugate
      vaccine for meningococcal disease in adolescents.
AB  - BACKGROUND: In a previous randomized phase 2 study in adolescents, a CRM197
      meningococcal conjugate vaccine against serogroups A, C, W-135 and Y (MenACWY
      CRM) was well tolerated and immunogenic, compared with a plain polysaccharide
      vaccine (MenACWY-PS). METHODS: This extension study assessed antibody persistence
      5 years after primary vaccination with MenACWY-CRM (n = 50) or MenACWY-PS (n =
      51), and the immunogenicity and reactogenicity of a dose of MenACWY-CRM given 5
      years after primary vaccination; antibody response was also compared with vaccine
      naive controls (n = 54). The primary endpoints were the percentage of subjects
      with titers >=8 by serum bactericidal activity assay using human complement
      (hSBA) 5 years after primary vaccination and hSBA geometric mean titers 1 month
      after the MenACWY-CRM dose given in the current study. RESULTS: Five years after
      primary vaccination, over 70% of subjects who had received MenACWY-CRM were
      seropositive (hSBA titers >=8) for serogroups C, W-135 and Y; for serogroups C
      and Y, the percentages of seropositive subjects were significantly higher in
      subjects previously vaccinated with MenACWY-CRM than in subjects previously
      vaccinated with MenACWY-PS. The MenACWY-CRM dose given 5 years postprimary
      vaccination elicited an anamnestic response across serogroups in those previously
      vaccinated with MenACWY-CRM. Responses in those previously vaccinated with
      MenACWY-PS were less robust but adequate and similar to that seen in the vaccine
      naive group, both in magnitude and kinetics. MenACWY-CRM was well tolerated in
      all 3 groups. CONCLUSION: MenACWY-CRM provided a broad and persistent immune
      response in adolescents. A subsequent dose of MenACWY-CRM elicited an adequate
      antibody response, regardless of vaccine history.

PMID- 23114373
TI  - Antiretroviral regimens containing a single protease inhibitor increase risk of
      virologic failure in young HIV-infected children.
AB  - Rifampin-based tuberculosis treatment can cause subtherapeutic concentrations of
      protease inhibitors and virologic failure in children receiving antiretroviral
      therapy. Among 217 children on antiretroviral therapy, tuberculosis cotreatment
      (in 78) was associated with virologic failure. Ritonavir-based single protease
      inhibitor antiretroviral therapy regimen predicted virologic failure (adjusted
      odds ratio 3.7, 95% confidence interval 1.5-8.9, P = 0.004) on multivariate
      analysis.

PMID- 23114374
TI  - Community outbreak of macrolide-resistant Mycoplasma pneumoniae in Yamagata,
      Japan in 2009.
AB  - BACKGROUND: We detected a community outbreak of macrolide-resistant Mycoplasma
      pneumoniae infection that occurred predominantly among students at 2 schools in
      Yamagata, Japan. METHODS: Throat swab specimens were collected from patients who
      were clinically suspected to have M. pneumoniae infection after testing negative
      for influenza virus by a nasopharyngeal swab rapid antigen test. We performed
      cultures for M. pneumoniae, and all isolates were sequenced for the presence of a
      mutation of the 23S rRNA gene. RESULTS: Of 96 specimens collected between July
      2009 and January 2010, 83 were from students attending junior high school A and
      primary schools B, C and D. A total of 47 M. pneumoniae isolates were obtained;
      among them, 25, 15 and 4 were isolated from students attending schools A, B and
      D, respectively, and M. pneumoniae could not be isolated from students who
      attended school C. An A2063T mutation in domain V of the 23S rRNA gene, which is
      associated with macrolide resistance, was identified in 39 (83.0%) isolates. The
      rates of macrolide resistance at schools A, B and D were 96.0%, 86.7% and 0%,
      respectively. The minimum inhibitory concentrations for isolates with an A2063T
      transversion showed high resistance to clarithromycin (minimum inhibitory
      concentration, 16-64 mg/L), and clarithromycin prescribed initially was
      clinically ineffective. CONCLUSIONS: This school-based cluster of macrolide
      resistant M. pneumoniae infections, which was identified in 2 geographically
      close schools, indicates that the transmission principally occurred by close
      contact between students at school. Monitoring the spread of macrolide-resistant
      M. pneumoniae and clinical guidelines for the appropriate medication against such
      infections would be needed to control outbreaks of M. pneumoniae.

PMID- 23114375
TI  - Protective effects of Ankaferd blood stopper on aspirin-induced oxidative mucosal
      damage in a rat model of gastric injury.
AB  - The exposure of gastric mucosa to damaging factors, such as ethanol and some
      therapeutic drugs, produces pathological changes: inflammatory process,
      hemorrhagic erosions and even acute ulcers. Ankaferd blood stopper (ABS)
      comprises a standardized mixture of five different plant extracts. The purpose of
      our present investigations is to explain the participation of reactive oxygen
      species in acute gastric mucosal damage by acetylsalicylic acid (ASA) and the
      effects of new hemostatic agent ABS. Experiments were carried out on 23 male
      Wistar rats. To assess gastric mucosal damage, biochemical and histopathological
      data were used. The colorimetric assays were used to determine the
      malondialdehyde (MDA) and superoxide dismutase (SOD) activity. The level of
      myeloperoxidase (MPO) activity, the level of nitric oxide (NO) and the
      proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) were measured by
      enzyme-linked immunosorbent assay technique. We demonstrated that the biological
      effects of ROS were estimated by measuring the tissue and plasma levels of MDA,
      the products of lipid peroxidation, as well as the activity of SOD and the
      scavenger of ROS produced by ASA in the experiment group. Moreover, it was found
      that MPO activity as well as NO and TNF-alpha levels also demonstrated
      significant improvement by ABS treatment. The pathogenesis of experimental ASA
      induced mucosal damage in rat stomach includes the generation of ROS that seems
      to play an important role, due to the generation of lipid peroxides, accompanied
      by the impairment of antioxidative enzyme activity of cells. ABS appeared to
      attenuate the oxidative and inflammatory changes caused by ASA-induced gastric
      mucosal damage in rats. 

PMID- 23114376
TI  - Relationship between carbon monoxide intoxication and sister chromatid exchange
      in lymphocytes.
AB  - AIM: Carbon monoxide (CO) intoxication can be serious and is reported to be the
      cause of more than half of all fatal intoxications. In this study, we aimed to
      identify its genotoxic effects based on sister chromatid exchange (SCE).
      MATERIALS AND METHODS: CO-poisoned patients presented to the emergency services
      department were identified. Their demographic characteristics, vital findings,
      laboratory markers, source of CO gas, risk factors, and smoking habits were
      recorded. The genotoxic effect was assessed using the SCE method. RESULTS: A
      total of 38 patients were recruited. Their ages ranged from 16-64 years (mean:
      29.79 +/- 10.92 years). In all the cases, the source of CO gas was a flash
      heater. The mean carboxyhemoglobin (COHb) level was 25.05 +/- 7.15%. Of all the
      patients, 12 (31.6%) had a the Glasgow Coma Scale (GCS) scores of less than 15,
      and an important negative correlation was found between the GCS and COHb level (r
      = -0.825; p < 0.001). Genotoxicity investigations revealed a significantly higher
      SCE frequency among patients with high COHb levels compared with that of control
      subjects with physiological COHb levels (p < 0.001). However, no correlation
      between increased SCE frequency and COHb level was found (r = 0.16; p = 0.34).
      CONCLUSION: CO poisoning was shown to result in genotoxicity via an increase in
      the frequency of SCE. This study is the first to demonstrate a genotoxic effect
      of CO independent of other chemicals.

PMID- 23114377
TI  - Effects of lichen extracts on haematological parameters of rats with experimental
      insulin-dependent diabetes mellitus.
AB  - The prevalence of diabetes mellitus in the world is steadily increasing.
      Oxidative stress contributes to the development of diabetic complications,
      including diabetic haematological changes. Lichens are used as food supplements
      and are also used as possible natural antioxidant, antimicrobial and anticancer
      agents. We hypothesized that antioxidant activity of lichens may decrease
      hyperglycaemia-induced oxidative stress and prevent the development of diabetic
      complications, including abnormality in haematological condition. Therefore, the
      effects of Cetraria islandica water extract (CIWE) and Pseudevernia furfuracea
      water extract (PFWE) on the haematological parameters of rats with type 1 DM were
      investigated for the first time in the present study. Control Sprague-Dawley or
      streptozotocin (STZ)-induced diabetic rats were either untreated or treated with
      water lichen extracts (5-500 mg/kg body weight (bw)/day) for 2 weeks, starting at
      72 h after STZ injection. On day 14, animals were anaesthetized and
      haematological and metabolic parameters were determined between control and
      experimental groups. In addition, the total oxidative stress (TOS), a specific
      indicator of oxidative stress, and the total antioxidant capacity (TAC) were
      measured by biochemical studies. In diabetic rats, CIWE of 250-500 mg/kg bw dose
      showed more prominent results when compared with doses of PFWE for TAC. The
      results obtained in the present study suggested that the antioxidant activities
      of lichens might be the possible reason behind the observed antihaematological
      status. However, the protective effect of lichen extracts were inadequate on
      diabetes-induced microcytic hypochromic anaemia. In addition, the extracts have
      no effect on metabolic complications. Our experimental data showed that high
      doses of CIWE and PFWE alone have no detrimental effect on blood cells and TOS
      status of plasma. Hence, they are safe and suitable for different administration
      routes. 

PMID- 23114378
TI  - Scaling of layer spacing of charged particles under slit-pore confinement: an
      effect of concentration or of effective particle diameter?
AB  - This paper tests the generality of the scaling law for layer spacing of charged
      particles under confinement and resolves the established contradictions in the
      literature. The present determined layer spacings lambda, also called the
      wavelength of oscillatory force, by colloidal probe atomic force microscopy are
      compared to previously obtained ones, Deltah, also called step size, by using a
      thin film pressure balance. For charged particles, e.g. silica nanoparticles and
      micelles of anionic surfactant, the layer spacing under confinement is found to
      depend solely on the particle number density rho in the relation lambda (or
      Deltah) =rho(-1/3). The previous description for the layer spacing using the
      effective particle diameter 2(R + kappa(-1)) is not general and only applicable
      at specific conditions of particle volume fraction and ionic strength. We claim
      that when particles are dominated by electrostatic repulsion and in a low
      pressure reservoir, rho(-1/3) is a general scaling law for layer spacing of
      particles, which indicates that particles under confinement are still randomly
      distributed in a fluid-like manner as they are in bulk. As a side-effect an
      equation to obtain the ionic strength I of colloidal suspension from measured
      conductivity is established. Ionic strength I is needed to determine the values
      for Debye length kappa(-1), which are in very good agreement with the theoretical
      ones.

PMID- 23114379
TI  - Pragmatic randomised trial of a 12-week exercise and nutrition program for
      Aboriginal and Torres Strait Islander women: clinical results immediate post and
      3 months follow-up.
AB  - BACKGROUND: Aboriginal and Torres Strait Islander women experience higher rates
      of heart disease and type 2 diabetes than non-Indigenous Australian women.
      Increasing physical activity, improving diets and losing weight have been shown
      to reduce cardio metabolic risk. The primary aim was to evaluate the
      effectiveness of a 12-week structured exercise and nutrition program in a cohort
      of urban Indigenous Australian women on waist circumference, weight and
      biomedical markers of metabolic functioning from baseline (T1) to program
      completion (T2). The secondary aim assessed whether these outcomes were
      maintained at 3-month follow-up. METHODS: One hundred Aboriginal and/or Torres
      Strait Islander women aged 18-64 years living in the Adelaide metropolitan area
      were recruited. The program included two 60-minute group cardiovascular and
      resistance training classes per week, and four nutrition education workshops.
      Participants were randomly assigned to an 'active' group or 'waitlisted' control
      group. Body weight, height, waist and hip circumference, blood pressure, fasting
      glucose, fasting insulin, glycated haemoglobin (HbA1C), lipid profile and C
      reactive protein (CRP) were assessed at baseline (T1), immediately after the
      program (T2) and three months post program (T3). RESULTS: The active group showed
      modest reductions in weight and body mass index (BMI). Compared to the waitlisted
      group, the active group had a statistically significantly change in weight and
      BMI from baseline assessments; at T2, (-)1.65 kg and (-)0.66 kg/m(2) and at T3, (
      )2.50 kg and (-)1.03 kg/m(2), respectively. Systolic and diastolic blood pressure
      also had a statistically significant difference from baseline in the active group
      compared to the waitlisted group at T2, (-)1.24 mmHg and (-)2.46 mmHg and at T3,
      (-)4.09 mmHg and (-)2.17 mmHg, respectively. The findings were independent of the
      baseline measure of the outcome variable, age, households with children and
      employment status. Changes in waist circumference and other clinical measures
      were not significant at T2 or T3. The primary outcome measure, waist
      circumference, proved problematic to assess reliably. Missing data and
      participants lost to follow-up were significant. CONCLUSIONS: This 12-week
      exercise program demonstrated modest reductions in weight, BMI and blood pressure
      at T2, which improved further at 3-month follow-up (T3). Positive intervention
      effects were observed despite low attendance at exercise classes. Structured
      exercise programs implemented in community settings require attention to
      understanding the barriers to participation for this high risk group. TRIAL
      REGISTRATION: Australian New Zealand Clinical Trials Registry
      ACTRN12610000224022.

PMID- 23114380
TI  - Genome reduction promotes increase in protein functional complexity in bacteria.
AB  - Obligate pathogenic and endosymbiotic bacteria typically experience gene loss due
      to functional redundancy, asexuality, and genetic drift. We hypothesize that
      reduced genomes increase their functional complexity through protein
      multitasking, in which many genes adopt new roles to counteract gene loss.
      Comparisons of interaction networks among six bacteria that have varied genome
      sizes (Mycoplasma pneumoniae, Treponema pallidum, Helicobacter pylori,
      Campylobacter jejuni, Synechocystis sp., and Mycobacterium tuberculosis) reveal
      that proteins in small genomes interact with proteins from a wider range of
      functions than do their orthologs in larger genomes. This suggests that surviving
      proteins form increasingly complex functional relationships to compensate for
      genes that are lost.

PMID- 23114381
TI  - Heritable loss of replication control of a minichromosome derived from the B
      chromosome of maize.
AB  - During an accumulation regime of a small telomere-truncated B chromosome, a
      derivative with large variations in size and multiple punctate centromere loci
      exhibiting amplified copy numbers was discovered. Multiple centromere satellite
      loci or transgene signals were documented in amplified chromosomes, suggesting
      over-replication. Immunolocalization studies revealed multiple foci of
      biochemical markers characteristic of active centromeres such as CENP-C and
      phosphorylation of histones H3S10 and H2AThr133. The amplified chromosomes
      exhibit an absence of chromosome disjunction in meiosis I and an infrequent
      chromosome disjunction in meiosis II. Despite their unusual structure and
      behavior these chromosomes were observed in the lineage for seven generations
      during the course of this study. While severely truncated relative to a normal B
      chromosome, the progenitor minichromosome is estimated to be at least several
      megabases in size. Given that the centromere and transgene signals at opposite
      ends of the chromosome generally match in copy number, the replication control is
      apparently lost over several megabases.

PMID- 23114382
TI  - Genetic regulation of vitamin D levels.
AB  - Vitamin D plays several roles in the body, influencing bone health as well as
      serum calcium and phosphate levels. Further, vitamin D may modify immune
      function, cell proliferation, differentiation, and apoptosis. Vitamin D
      deficiency has been associated with numerous health outcomes, including bone
      disease, cancer, autoimmune disease, infectious disease, type 1 and type 2
      diabetes, hypertension, and heart disease, although it is unclear whether or not
      these associations are causal. Various twin and family studies have demonstrated
      moderate to high heritability for circulating vitamin D levels. Accordingly, many
      studies have investigated the genetic determinants of this hormone. Recent
      advances in the methodology of large-scale genetic association studies, including
      coordinated international collaboration, have identified associations of CG,
      DHCR1, CYP2R1, VDR, and CYP24A1 with serum levels of vitamin D. Here, we review
      the genetic determinants of vitamin D levels by focusing on new findings arising
      from candidate gene and genomewide association studies.

PMID- 23114383
TI  - A glass fiber sheet-based electroosmotic lateral flow immunoassay for point-of
      care testing.
AB  - We have developed a quantitative immunoassay chip targeting point-of-care
      testing. To implement a lateral flow immunoassay, a glass fiber sheet was chosen
      as the material for the microfluidic channel in which the negative charge on the
      fiber surfaces efficiently generates the electroosmotic flow (EOF). The EOF, in
      turn, allows controllable bound/free separation of antigen/antibody interactions
      on the chip and enables precise determination of the antigen concentration. In
      addition, the defined size of the porous matrix was suitable for the filtration
      of undesired large particles. We confirmed the linear relationship between the
      concentration of analyte and the resulting fluorescence intensity from the
      immunoassay of two model analytes, C-reactive protein (CRP) and insulin,
      demonstrating that analyte concentration was quantitatively determined within the
      developed chip in 20 min. The limits of detection were 8.5 ng mL(-1) and 17 ng
      mL(-1) for CRP and insulin, respectively.

PMID- 23114384
TI  - Prevalence of chronic bronchitis in farm and nonfarm rural residents in
      Saskatchewan.
AB  - OBJECTIVE: To determine the prevalence of chronic bronchitis (CB) and associated
      risk factors in farm and nonfarm rural residents in Saskatchewan, Canada.
      METHODS: The questionnaire collected information about health, contextual, and
      individual factors from 8261 farm and nonfarm adult residents (18 years and
      older). RESULTS: The prevalence of CB was 5.3% among farm residents and 6.4%
      among nonfarm residents. We found a greater prevalence of CB associated with
      household income adequacy, increasing age, allergies, history of lung disease in
      a parent, exposure to stubble smoke, obesity, prenatal exposure to smoking, and
      female sex. Smoking interacted with occupational exposure to wood dust and
      solvents, and allergic reaction to molds. CONCLUSION: The results suggest that
      increasing household income and reducing smoking could be primary, modifiable
      determinants of CB prevalence.

PMID- 23114385
TI  - Supporting people with diabetes mellitus in applying for and participating
      effectively in paid work: validation of successful diabetes-related behaviors by
      experiential experts and professional care providers.
AB  - OBJECTIVE: To validate successful diabetes-related behaviors, proposed by a group
      of experiential experts, and to support people with diabetes in applying for and
      participating effectively in work. METHODS: In a survey among 77 experiential
      experts and 21 professional care providers, the behaviors were critically
      appraised regarding several key characteristics. RESULTS: Experiential experts
      (median scores: 91%, 86%, and 86%) and professionals (median scores: 76%, 76%,
      and 81%) mostly agreed with these behaviors in terms of clarity, content, and
      relevance, respectively. Feasibility was seen as somewhat problematic, with
      median scores by experiential experts and professionals of 65% and 52%,
      respectively. CONCLUSION: Both groups confirmed the validity of the proposed work
      related behaviors that were expected to support people with diabetes. The
      challenge is to implement these behaviors in practice, by effective dissemination
      and incorporation in work-related self-management programs.

PMID- 23114386
TI  - Serum heme oxygenase-1 as a marker of lung function decline in patients with
      chronic silicosis.
AB  - OBJECTIVE: To identify predictive factors of excess decline in forced expiratory
      volume in one second (FEV1) in patients with chronic silicosis. METHODS: Forty
      six male patients enrolled in 2004 were screened and received pulmonary function
      tests. RESULTS: Among the 33 included patients, 12 were categorized as rapid
      decliners (reduction in FEV1 > 60 mL/yr). The mean level of serum heme oxygenase
      1 (HO-1), a marker of oxidative stress, was significantly lower in rapid
      decliners than in normal decliners (P = 0.002). Logistic regression analysis
      revealed that serum HO-1 was a factor affecting clinically important decline in
      FEV1 (odds ratio = 0.52; 95% confidence interval, 0.31 to 0.88) independent of
      the effects of age, height, weight, smoking, exposure status, and C-reactive
      protein. CONCLUSIONS: Serum HO-1 may be a predictor of lung function decline in
      silicosis patients.

PMID- 23114387
TI  - The value of periodic spirometry for early recognition of long-term excessive
      lung function decline in individuals.
AB  - OBJECTIVE: To establish the value of workplace spirometry monitoring methods for
      early recognition of long-term excessive lung function decline in individuals.
      METHODS: Sensitivity, specificity, and positive likelihood ratio were calculated
      to determine the predictive value of the linear regression slope and limits of
      longitudinal decline for early prediction of long-term excessive forced
      expiratory volume in 1 second (FEV1) decline (> 90 mL/yr established over 9 to 11
      years) in ongoing spirometry monitoring programs (firefighters and construction
      workers) and a historical program (paper-pulp mill workers). The longitudinal
      limits account for the expected FEV1 within-person variability. RESULTS: The
      longitudinal limits achieved clinical "usefulness" (positive likelihood ratio 10
      or higher) from the fourth to fifth year of follow-up, whereas the linear
      regression slope was less useful. The usefulness depended on data precision and
      measurement frequency. CONCLUSION: The limits of longitudinal decline are more
      useful for early recognition of long-term excessive FEV1 decline than the linear
      regression slope.

PMID- 23114388
TI  - Does an exercise intervention improving aerobic capacity among construction
      workers also improve musculoskeletal pain, work ability, productivity, perceived
      physical exertion, and sick leave?: a randomized controlled trial.
AB  - OBJECTIVE: To investigate whether an exercise intervention shown to increase
      aerobic capacity, would also lead to less musculoskeletal pain; improved work
      ability, productivity, and perceived physical exertion; and less sick leave.
      METHODS: Sixty-seven construction workers were randomized into an exercise group
      training 3 * 20 minutes per week and a control group. Questionnaires and text
      messages were completed before and after the 12-week intervention. RESULTS: No
      significant changes were found in musculoskeletal pain, work ability,
      productivity, perceived physical exertion, and sick leave with the intervention.
      Questionnaires and text messages provided similar results of pain and work
      ability. CONCLUSIONS: Although the intervention improved aerobic capacity, it was
      not successful in improving musculoskeletal pain and other work-related factors.
      A detectable improvement presumably requires a more multifaceted intervention,
      larger sample size, or longer follow-up. Text messages may be a convenient data
      collection method in future studies.

PMID- 23114389
TI  - Occupation and leukemia in Nordic countries.
AB  - OBJECTIVE: We studied occupational variation of the risk of acute myeloid
      leukemia, chronic lymphocytic leukemia, and other leukemia in Nordic countries.
      METHODS: The study cohort comprised 15 million persons older than 30 years who
      participated in the population censuses in 1960, 1970, 1980/1981, 1990, or all of
      these years in five Nordic countries. Standardized incidence ratios (SIRs) were
      estimated for 53 occupations and one group of economically inactive persons.
      RESULTS: Significantly increased risks were observed for acute myeloid leukemia
      among drivers (SIR = 1.16; 95% confidence interval [CI], 1.07-1.26) and food
      workers (SIR = 1.13; 95% CI, 1.01-1.27); for chronic lymphocytic leukemia among
      farmers (SIR = 1.09; 95% CI, 1.04-1.14) and clerical workers (SIR = 1.07; 95% CI,
      1.01-1.14); and for other leukemia among seamen (SIR = 1.24; 95% CI, 1.04-1.49),
      "other health workers" (SIR = 1.22; 95% CI, 1.02-1.47), chemical process workers
      (SIR = 1.18; 95% CI, 1.01-1.38), and sales agents (SIR = 1.15; 95% CI, 1.06
      1.25). CONCLUSION: Observed modest occupational variation of leukemia risk might
      be associated with occupational or lifestyle factors.

PMID- 23114390
TI  - Prevalence and risk factors for the development of diabetes mellitus in Swedish
      cats.
AB  - BACKGROUND: The prevalence and risk factors for the development of feline
      diabetes mellitus (FDM) in Swedish cats have not previously been reported. The
      objective of the present pilot study was to indicate prevalence and possible risk
      factors for FDM in Swedish cats. Twenty diabetic cats from the database at the
      University Animal Hospital in Uppsala participated in the study, and these were
      matched with 20 healthy controls on sex and age. A mail-and-telephone
      questionnaire focusing on diet, activity and obesity was used. RESULTS: The
      prevalence of FDM during the years 2000-2004 based on the results of the hospital
      records in the present study was 21 per 10,000 cats. The diabetic cats were on
      average 9 years old when the disease signs were discovered (median, min-max 2
      15). Among FDM cases, it was more common to be male (n=17 males vs n=3 females;
      P<=0.05). Ten out of twenty owners to cases (50%) reported their cats to be obese
      at the time of the diagnosis (median 9 years, min-max 2-15), as compared to five
      out of twenty (25%) controls at the same age. The median BW at the time for
      diagnosis was 5.5 kg (min-max 2.0-9.0) for cases, and 5.0 kg (min-max 3.0-8.0 kg)
      for controls, respectively. Despite that both cases and controls had the same
      median age at the time of the study (13 years, min-max 3-18), a significantly
      higher number of controls were alive at that age (n=16 controls vs 8 cases;
      P<=0.05). A significantly higher proportion of cases that were obese at the time
      of the FDM diagnosis were dead at the time of the study compared to the
      proportion of controls that were obese at a similar age (P<=0.05).The diets given
      at the time for diagnosis for cases compared to diet of the controls at a similar
      time were mainly commercial foods, and controls consumed a higher proportion of
      dry foods compared to cases (medians 79 vs 44% of DM intake/d, respectively;
      P<=0.05). Cases were less active compared to the controls (2.3 and 3.2 h/d,
      respectively; P<=0.05). CONCLUSIONS: The results indicate that the proportions of
      dry foods in the diet, to perform low activity and to be obese could be
      identified as preliminary risk factors for FDM in Swedish cats, and should be
      taken into account in preventive measures as well as in the design of future
      epidemiological studies in this population.

PMID- 23114391
TI  - Factors influencing nurses' intentions toward the use of mobile electronic
      medical records.
AB  - The purpose of this study was to investigate the factors influencing nurses'
      intentions toward the use of mobile electronic medical records, based on the
      Theory of Diffusion of Innovations. The cross-sectional study used a structured
      questionnaire for data collection, focusing on the nurses of a large hospital in
      southern Taiwan. A total of 720 valid questionnaires were returned yielding a
      response rate of 82.0%. Multiple regression analysis of the responses identified
      three innovative characteristics, compatibility, complexity, and observability,
      as significantly influencing nurses' intentions toward adopting mobile electronic
      medical records, whereas relative advantage and trialability did not. In
      addition, nursing seniority affected nurses' intentions significantly toward
      adopting mobile electronic medical records. Implications of effects of the
      factors and future research directions are discussed.

PMID- 23114392
TI  - Development and evaluation of simulation-based training for obstetrical nursing
      using human patient simulators.
AB  - As the observation of obstetrical patients with diverse complications is
      increasingly rare in clinical training, computerized high-fidelity simulators can
      greatly benefit obstetrical nurse education. However,simulation scenarios in
      obstetrical nursing are not well studied. This study aims to develop simulation
      scenarios for obstetrical nursing that (1) demonstrate clinical situations from
      prenatal, labor and delivery, to postpartum phases and (2) provide educational
      tools for student evaluation and weakness identification. We developed four
      simulation scenarios: prenatal, labor and delivery I, labor and delivery II, and
      postpartum. Each scenario is designed to demonstrate students' knowledge,
      techniques, and interpersonal skills. One hundred thirty-eight second-year
      nursing students were trained with four scenarios using a high-fidelity
      simulator, after which each student was evaluated by one selected scenario. In
      the experiments, students' self-confidence increased after the program in all
      scenarios (P < .001). Students scored higher in prenatal and postpartum scenarios
      than labor and delivery I and II scenarios. In particular, most students could
      perform relevant actions, but many students failed to perform the actions
      correctly. Our results show that the designed scenarios are effectual for
      promoting students' self-confidence and improving the quality of obstetrical
      nursing education.

PMID- 23114393
TI  - Adverse-drug-event surveillance using narrative nursing records in electronic
      nursing records.
AB  - The purpose of this study was to determine whether the frequency of adverse drug
      events can be extracted by analyzing narrative nursing statements documented in
      standardized terminology-based electronic nursing records. For this study, we
      reviewed the narrative nursing documentations of 487 admissions of 355 cancer
      patients who were treated with cisplatin at a tertiary-care hospital in Korea.
      Narrative nursing statements with the terms "adverse drug reaction," "allergy,"
      "hypersensitivity," and other adverse drug events listed in the safety
      information were analyzed. In addition, nausea, one of the most frequent adverse
      drug events, was further examined. Narrative statements documenting the presence
      or absence of an "adverse drug reaction," "allergy," and "hypersensitivity" were
      found in 162 admissions (33.3%). The presence or absence of adverse drug events
      due to cisplatin was documented in 476 admissions (97.7%). At least one adverse
      drug event was noted in 258 admissions (53.0%). The presence of nausea was
      documented in 214 admissions (43.9%), and the mean duration of nausea was 5.2
      days. The results of this study suggest that adverse drug events can be monitored
      using narrative nursing statements documented in standardized terminology-based
      electronic nursing records.

PMID- 23114394
TI  - Using *ORA, a network analysis tool, to assess the relationship of handoffs to
      quality and safety outcomes.
AB  - Communication during patient handoffs has been widely implicated in patient
      safety issues. However, few studies have actually been able to quantify the
      relationship between handoffs and patient outcomes. We used *ORA, a dynamic
      network analysis tool, to examine handoffs between day and night shifts on seven
      units in three hospitals in the Southwest. Using *ORA's visualization and
      analysis capabilities, we examined the relationships between the handoff
      communication network metrics and a variety of patient safety quality and
      satisfaction outcomes. Unique network patterns were observed for different types
      of outcome variable (eg, safety, symptom management, self-care, and patient
      satisfaction). This exploratory project demonstrates the power of *ORA to
      identify communication patterns for large groups, such as patient care units.
      *ORA's network metrics can then be related to specific patient outcomes.

PMID- 23114395
TI  - Spiro-fluorene based 3D donor towards efficient organic photovoltaics.
AB  - A novel 3D donor material (SF8TBT) based on spiro-fluorene has been developed.
      Compared with the corresponding 1D linear molecule, the OPVs of this 3D donor
      exhibited power conversion efficiencies of 4.82%, much higher than that of 1D
      small molecules (1.69%).

PMID- 23114396
TI  - Patellar tendon rupture following a patellar fracture.

PMID- 23114397
TI  - [Functional tricuspid regurgitation: the increasing clinical importance of the
      "forgotten valve"].
AB  - Functional tricuspid regurgitation (FTR) is the most frequent etiology of
      tricuspid valve pathology in Western countries. In the last years, many
      investigators have reported evidence in favor of a more aggressive surgical
      approach to FTR and interest has been growing in the physiopathology and
      treatment of FTR. The purpose of this editorial is to explore the anatomical
      basis, pathophysiology, therapeutic approaches and the perspectives of treatment.

PMID- 23114398
TI  - [Geriatric telecare, a new model of assistance: a pilot study].
AB  - Aim of this pilot study was to evaluate the feasibility and explore the patients'
      acceptance of the -telecare model. The objective of this trial was to investigate
      the effects of a telecare system on elderly management at home. In a 24-months
      prospective study we enrolled all patients aged >65 years at risk of disability.
      During the two years of observation, each patient contact the TELECARE system.
      Telephone contact was followed by specific intervention and administration of a
      questionnaire evaluation. Over the 24 months we recorded 90,000 calls and 13,000
      elderly were included in the telecare project. We analyzed the calls and the
      measures adopted. Our findings provide evidence of improved quality of life
      through clinical management at home from a telecare system. The use of this
      system had high adherence and was feasible for elderly patients and their family.

PMID- 23114399
TI  - [Clinical profiling of a complex, asyntomatic patient beyond the standard
      assessment of cardiovascular risk].
AB  - The multi-dimensional evaluation of an elderly hypertensive subject, asyntomatic
      yet complex, evidences the need for a clinical assessment going beyond the limits
      of the traditional analysis of cardiovascular risk. The case here described
      provides a reasoned guide for the integration of all risk elements and factors in
      the global definition of the risk profile of an individual in primary prevention,
      and only apparently at moderate cardiovascular risk.

PMID- 23114400
TI  - [Childhhood obesity, insulin resistance and increased cardiovascular risk].
AB  - Excess fat is one of the major risk factors for insulin resistance predisposing
      to the development of cardiovascular diseases in western countries. We know that
      obese patients are strongly at risk of cardiovascular diseases, like myocardial
      infarction or stroke. These diseases are the most frequent cause of death in the
      adult population, representing a social and economic problem. Today there are not
      available and useful markers for screening and diagnosis of insulin- resistance
      in young people. "Easy-to-detect" clinical markers must be found to identify
      young subjects at risk of cardiovascular diseases. Very interesting the
      relationship between wrist circumference, its bone composition and insulin
      resistance.

PMID- 23114401
TI  - [Bone health in the oncologic patient].
AB  - Progressive bone loss, resulting in both osteoporosis and osteomalacia, is a
      frequent long-term complication in cancer patients undergoing common anti-tumor
      treatment programs. Monitoring of bone health by both imaging techniques and
      biochemical markers measurement, is useful in preventing the severe skeleton
      default.

PMID- 23114402
TI  - [Patient involvement in medical decision-making].
AB  - The increasing interest in the Shared Decision Making approach is linked to an
      improvement of the clinical outcomes. This paper proposes an update of the
      literature review on Shared Decision-Making in the clinical setting in Italy,
      describing the areas of application, the objectives, the instruments used and the
      main results.

PMID- 23114403
TI  - Mandatory quality reports in Germany from the hospitals' point of view: a cross
      sectional observational study.
AB  - BACKGROUND: Public reporting of hospital quality is to enable providers, patients
      and the public to make comparisons regarding the quality of care and thus
      contribute to informed decisions. It stimulates quality improvement activities in
      hospitals and thus positively impacts treatment results. Hospitals often use
      publicly reported data for further internal or external purposes.As of 2005,
      German hospitals are obliged to publish structured quality reports (QR) every two
      years. This gives them the opportunity to demonstrate their performance by
      number, type and quality in a transparent way. However, it constitutes a major
      burden to hospitals to generate and publish data required, and it is yet unknown
      if hospitals feel adequately represented and at the same time consider the effort
      appropriate.This study assesses hospital leaders' judgement about the capability
      of QR to put legally defined aims effectively and efficiently into practice. It
      also explores the additional purposes hospitals use their QR for. METHODS: In a
      cross-sectional observational study, a representative random sample out of 2,064
      German hospitals (N=748) was invited to assess QR via questionnaire; 333
      hospitals participated. We recorded the suitability of QR for representing
      number, type and quality of services, the adequacy of cost and benefits (6-level
      Likert scales) and additional purposes QR are used for (free text question). For
      representation purposes, the net sample was weighted for hospital size and
      hospital ownership (direct standardization). Data was analyzed descriptively and
      using inferential statistics (chi-2 test) or for the purpose of generating
      hypotheses. RESULTS: German hospitals rated the QR as suitable to represent the
      number of services but less so for the type and quality of services. The cost
      benefit ratio was seen as inadequate. There were no significant differences
      between hospitals of different size or ownership.Public hospitals additionally
      used their reports for mostly internal purposes (e.g. comparison with
      competitors, quality management) whereas private ones used them externally (e.g.
      communication, marketing) (p=0.024, chi-2 test, hypotheses-generating level).
      CONCLUSIONS: German hospitals consider the mandatory QR as only partially capable
      to put the legally defined aims effectively and efficiently into practice. In
      order for public reporting to achieve its potentially positive effects, the QR
      must be more closely aligned to the needs of hospitals.

PMID- 23114404
TI  - Correlation between multiple RET mutations and severity of Hirschsprung's
      disease.
AB  - PURPOSE: The enteric nervous system (ENS), comprising neurons and glial cells,
      organized as interconnected ganglia within the gut wall, controls peristalsis and
      the production of secretions. The RET receptor tyrosine kinase is expressed
      throughout enteric neurogenesis and is required for normal ENS development.
      Humans with mutations in the RET locus have Hirschsprung's disease (HSCR), and
      mice lacking RET exhibit total intestinal aganglionosis. Although a number of
      mutations with the potential for causing HSCR have been reported, their precise
      correlation with phenotype and symptom severity in HSCR is not clearly
      understood. Our study investigates the correlation between mutations in the RET
      locus and symptom severity in HSCR. METHODS: We performed a comprehensive
      nucleotide analysis of the RET coding region in 18 HSCR patients and 87 controls,
      performed cellular biological analysis by Western blotting using the expression
      vector, and analyzed cell proliferation with anti-Ki67 antibody under
      immunofluorescence confocal microscopy (ICM). RESULTS: We identified three novel
      mutations, D489N, L769L, and V778D in the RET coding region in our HSCR patients.
      In the allelic distribution of D489N and L769L, the difference between HSCR
      patients and controls reached statistical significance (p = 0.0373 and p =
      0.0004, respectively), whereas no statistical difference was observed in the
      allelic distribution of V778D (p = 0.1073). One HSCR patient who died from total
      colonic aganglionosis had a combination of homozygous mutation of D489N, L769L,
      and heterozygous mutation of V778D. Western blotting of full mutant RET from this
      patient showed significantly increased 150kD-band, which corresponds to the
      immature form compared with wild-type and single mutant RET. ICM showed that
      overexpression of full mutant RET significantly reduced cellular proliferation in
      comparison with wild-type and single mutant RET. CONCLUSION: A combination of
      mutations in the RET locus may correlate with symptom severity in HSCR as a
      consequence of reduced cellular proliferation secondary to altered maturation of
      RET.

PMID- 23114405
TI  - Increased trophoblastic apoptosis mediated by neutrophil gelatinase-associated
      lipocalin (NGAL) activation in the nitrofen model of congenital diaphragmatic
      hernia.
AB  - BACKGROUND: Retinoids play a key role in fetal lung development. It has been
      suggested that the maternal-fetal retinol transport is disrupted by trophoblastic
      apoptosis. The mechanism underlying nitrofen-induced apoptosis in placenta is not
      fully understood. Neutrophil gelatinase-associated lipocalin (NGAL) is expressed
      in the fetal part of the maternal-fetal interface. NGAL is part of the immune
      barrier and serves primarily as a transport protein transferring biologically
      hazardous molecules in a safe and controlled way. It has been shown that over
      activation of NGAL induces apoptosis. We hypothesized that increased placental
      NGAL expression induces trophoblastic apoptosis in the nitrofen model of CDH.
      METHODS: Pregnant rats were exposed to either olive oil or nitrofen on day 9 of
      gestation (D9). Placenta harvested on D21 and divided into two groups: control
      and nitrofen with CDH. Immunohistochemistry was performed to evaluate
      trophoblasts (by cytokeratin expression), NGAL expression, and apoptotic
      trophoblastic cells (using TUNEL assay). Total RNA was extracted from each
      placenta and the relative mRNA expression levels of NGAL were analyzed using RT
      PCR. RESULTS: Immunohistochemistry showed NGAL immunoreactivity both in control
      and CDH in the fetal part of the fetal-maternal interface of placenta. Markedly
      increased NGAL expression was detected in CDH group compared to controls.
      Relative mRNA expression levels of NGAL gene were significantly increased in the
      CDH group compared to control in the placenta (5.924 +/- 0.93 vs. 1.895 +/- 0.54,
      p < 0.001). Markedly increased numbers of apoptotic trophoblastic cells were seen
      in the maternal-fetal interface in the CDH group compared to controls.
      CONCLUSIONS: NGAL activation may lead to increased trophoblastic apoptosis in the
      maternal-fetal interface in the nitrofen model of CDH. These changes may
      therefore cause disturbance in maternal-fetal retinol transport affecting fetal
      lung morphogenesis.

PMID- 23114406
TI  - Dietary supplementation with vitamin D stimulates intestinal epithelial cell
      turnover after massive small bowel resection in rats.
AB  - PURPOSE: While the endocrine action of the active metabolite 1,25
      dihydroxyvitamin D (VtD) has been well characterized in relation to the
      maintenance of plasma calcium and phosphate homeostasis through regulation of
      intestinal absorption, recent research has focused on its autocrine and/or
      paracrine activities. Such activities have been best characterized in intestine,
      where VtD regulates cell differentiation and maturation. The purpose of this
      study was to evaluate the effect of VtD on enterocyte turnover in a rat model of
      short bowel syndrome (SBS). METHODS: Male rats were divided into four groups:
      sham rats underwent bowel transection, sham-VtD rats underwent bowel transection
      and were treated oral VtD, SBS rats underwent a 75 % bowel resection, and SBS-VtD
      rats underwent bowel resection and were treated with VtD. Parameters of
      intestinal adaptation, enterocyte proliferation and apoptosis were determined at
      sacrifice. Illumina's digital gene expression (DGE) analysis was used to
      determine VtD pathway-related gene expression profiling. VtD receptor (VDR) and
      its promoter, Bax and Bcl-2 mRNA expression were determined using real-time PCR.
      Western blotting was used to determine p-ERK, Bax and beta-catenin protein
      levels. RESULTS: From the total of 20,000 probes, 11 genes related to VtD
      signaling were investigated. Of these genes, five were found to be up-regulated
      in SBS versus sham animals with a relative change in gene expression level of 20
      %, five remained unchanged, and one was down-regulated. VtD treatment in sham and
      SBS rats resulted in significant up-regulation of the VDR gene and its promoter's
      expression. SBS-VtD rats demonstrated a significant increase in all intestinal
      mucosal parameters compared to SBS animals. A significant increase in cell
      proliferation in SBS-VtD rats was accompanied by increased beta-catenin protein
      levels. A significant decrease in cell apoptosis in this group was correlated
      with lower Bax/Bcl-2 mRNA and protein levels. CONCLUSION: In a rat model of SBS,
      dietary supplementation with VtD stimulates enterocyte turnover, which correlates
      with up-regulated VtD receptor expression in the remaining small intestine.

PMID- 23114407
TI  - Vitrectomy and panretinal photocoagulation reduces the occurrence of neovascular
      glaucoma in central retinal vein occlusion with vitreous hemorrhage.
AB  - PURPOSE: The purpose of this study was to evaluate the best-corrected visual
      acuity and occurrence of neovascular glaucoma with vitrectomy (VT) and panretinal
      photocoagulation or without VT in central retinal vein occlusion (CRVO)
      associated with vitreous hemorrhage (VH). METHODS: The charts from patients
      diagnosed as having CRVO with VH at Chang Gung Memorial Hospital (Taiwan) were
      reviewed. They were grouped based on whether they also underwent VT. The main
      outcome measurements were the best-corrected visual acuity and incidence of
      neovascular glaucoma. RESULTS: There were 83 eyes that had CRVO with VH from 83
      patients (VT group, 56 eyes; non-VT group, 27 eyes). There was no significant
      difference between the VT and non-VT groups in terms of age, gender, diabetes,
      hypertension, lens status, and follow-up period. The non-VT group had a better
      best-corrected visual acuity (P = 0.018) and less VH (P = 0.025) than the VT
      group at baseline; however, the VT group had a better best-corrected visual
      acuity at the end of the follow-up than the non-VT group (P < 0.001). Most
      importantly, there was a higher neovascular glaucoma development (37%) in the non
      VT group compared with that (14.3%) in the VT group (P = 0.025). CONCLUSION: The
      visual outcomes of CRVO with VH are unfavorable whether VT was performed.
      However, VT and panretinal photocoagulation improved visual acuity and reduced
      the incidence of neovascular glaucoma in CRVO with VH.

PMID- 23114408
TI  - The time course changes of choroidal neovascularization in angioid streaks.
AB  - PURPOSE: To assess the clinical course of choroidal neovascularization (CNV) in
      patients with angioid streaks using optical coherence tomography and fluorescein
      angiography/indocyanine green angiography. METHODS: We examined a consecutive
      series of 88 eyes of 44 patients with angioid streaks using color fundus
      photography, optical coherence tomography, and fluorescein
      angiography/indocyanine green angiography. RESULTS: At the initial visit, 33 eyes
      exhibited no CNV, 2 exhibited polypoidal choroidal vasculopathy, 8 exhibited Type
      1 CNV, 32 exhibited active Type 2 CNV, and 13 exhibited a fibrotic scar. In
      addition to the 2 eyes that exhibited macular polypoidal choroidal vasculopathy
      at the initial visit, 3 exhibited peripapillary polypoidal lesions, and 2
      exhibited polypoidal lesions at the edge of the preexisting Type 2 CNV/fibrosis.
      During the follow-up, Type 2 CNV developed in 4 eyes on the basis of Type 1 CNV.
      Visual acuity was worse in eyes with Type 2 CNV and fibrosis than in those with
      Type 1 CNV, while polypoidal choroidal vasculopathy did not affect the visual
      acuity. CONCLUSION: Eyes with angioid streaks can develop any form of CNV
      including polypoidal choroidal vasculopathy. Considering the worse visual acuity
      in eyes with Type 2 CNV and fibrosis, patients should be carefully observed so as
      to treat them promptly when Type 2 CNV occurred beneath the fovea.

PMID- 23114409
TI  - Vitreoretinal surgery fellowship training and the big disconnect:  is it just a
      numbers game?

PMID- 23114410
TI  - Influence of the duration of breastfeeding on quality of muscle function during
      mastication in preschoolers: a cohort study.
AB  - BACKGROUND: There is some evidence of the benefits of breastfeeding to
      masticatory function, but no studies have evaluated the influence of
      breastfeeding duration on the quality of this function. The objective of this
      study was to investigate the association between duration of breastfeeding and
      quality of masticatory function in preschoolers. METHODS: Cross-sectional study
      nested in a contemporary cohort of 144 randomly selected Brazilian infants. Data
      on sociodemographic, dietary, and sucking-related parameters were collected
      shortly after birth and at 7, 30, 60, 120, and 180 days of life. Masticatory
      function was assessed between the ages of 3 and 5 years, using a standardized
      procedure involving three foodstuffs of different consistencies, for evaluation
      of incision, lip competence, masticatory patterns, masticatory movements, and
      perioral muscle use. The quality of masticatory function was scored, and multiple
      linear regression was used to test for association between this score and the
      duration of breastfeeding. RESULTS: A positive correlation was found between
      duration of breastfeeding and masticatory function scores (rs = 0.473; p <
      0.001). Children breastfed for at least 12 months had significantly higher
      average scores, regardless of bottle-feeding or pacifier use. Children who were
      breastfed for longer were more likely to score satisfactorily across all tested
      parameters. CONCLUSIONS: Breastfeeding has a positive impact on mastication. In
      our sample, duration of breastfeeding was positively associated with the quality
      of masticatory function at preschool age.

PMID- 23114411
TI  - Prominent features of platelet count, plateletcrit, mean platelet volume and
      platelet distribution width in pulmonary tuberculosis.
AB  - BACKGROUND: We aimed to investigate the relation of platelet count (PLT) and
      plateletcrit (PCT), mean platelet volume (MPV) and platelet distribution width
      (PDW) with other acute phase reactants and radiological extent in pulmonary
      tuberculosis (PTB). METHODS: One hundred patients with PTB (Group 1), 50 patients
      with community-acquired pneumonia (Group 2) and 28 healthy control individuals
      (Group 3) were included in this analytic study. RESULTS: WBC (White Blood Cell),
      ESR (Eritrocyte Sedimentation Rate), CRP (C-Reactive Protein), PLT and PCT values
      were both in Group 1 and Group 2 than in Group 3. PDW values were significantly
      higher in Group 1 than Group 3. WBC, ESR and CRP values were lower, while PLT and
      PCT values were higher in the Group 1 compared to Group 2 (p < 0.001). PLT was
      positively correlated with CRP and ESR values in the tuberculosis group (p <
      0.001), while it was not correlated with CRP and ESR in the pneumonia group (p >
      0.05). ESR, CRP, PLT and PCT values were found higher in radiological advanced
      stage (Stage 3) patients with PTB, while hemoglobin (Hb) was found lower  (p <
      0.05). Higher WBC, ESR, CRP and PCT values as well as radiological advanced stage
      were more common in PTB patients with thrombocytosis compared to the patients
      with normal platelet count, whereas Hb was found lower in these patients.
      CONCLUSIONS: This study indicates that reactive thrombocytosis and higher PCT and
      PDW develop frequently in PTB and there is a relation between thrombocytosis and
      acute phase reactants, that is the inflammatory response. In addition,
      tuberculosis with radiological advanced stage is seen more frequently in the
      patients with thrombocytosis and higher PCT, drawing attention to the possible
      role of platelets in the cell-based immune process of tuberculosis.

PMID- 23114413
TI  - Anterior knee pain.

PMID- 23114412
TI  - Biomechanical evaluation of locking plate fixation of proximal humeral fractures
      augmented with calcium phosphate cement.
AB  - OBJECTIVES: To evaluate the influence of calcium phosphate cement augmentation on
      failure of locking plate fixation of proximal humeral fracture fixation in a
      cadaveric fracture model. METHODS: A 5-mm wedge osteotomy was created in each of
      11 paired fresh-frozen human cadaveric humeri (age > 65 years). Specimens were
      randomly assigned to receive either locked plate fixation (group 1) or locked
      plate fixation with cement augmentation (group 2). Constructs were tested for
      axial stiffness, load to failure, and failure mode using a material testing
      machine. RESULTS: Cement-augmented specimens resisted higher loads (1936 +/- 609
      N) in comparison to nonaugmented specimens (1373 +/- 590 N) (P = 0.01). In group
      1, varus displacement and glenohumeral screw perforation occurred in all cases.
      Varus displacement occurred in 2 cases in group 2, whereas glenohumeral screw
      perforation did not occur in any of the cases. Cement augmentation led to a
      significant increase in axial stiffness (P = 0.04). CONCLUSIONS: Calcium
      phosphate cement-augmented locking plates enhanced fixation stability in proximal
      humeral fractures and reduced glenohumeral screw perforation in this 2-part
      cadaveric model. The ultimate advantage of this method remains to be determined
      in vivo.

PMID- 23114414
TI  - Health literacy in an orthopedic trauma patient population: a cross-sectional
      survey of patient comprehension.
AB  - OBJECTIVES: The aim of this study was to evaluate the level of comprehension in
      an orthopedic trauma patient population regarding injury, surgery, and
      postoperative instructions and to determine if educational background is
      associated with inadequate comprehension. DESIGN: This involved a prospective
      observational cohort. SETTING: The study was conducted at an Academic Level 1
      trauma center. PATIENTS: From April to June 2011, 248 orthopedic trauma patients
      with an operatively fixed isolated fracture were found to be eligible for
      inclusion. One hundred forty-six eligible questionnaires were collected (58.9%
      response rate). INTERVENTION: The patients were administered a questionnaire
      during their first postoperative visit before being seen by a physician. The
      questionnaire included demographic information and questions regarding (1) which
      bone was fractured; (2) the type of implanted fixation; (3) weight-bearing
      status; (4) expected recovery time; and (5) need for deep vein thrombosis (DVT)
      prophylaxis. Multivariable logistic regression analyses were used to examine the
      association between educational level and questions regarding surgical procedure
      and discharge instructions. RESULTS: The overall mean score of all the patients
      on the patient comprehension portion was 2.54 +/- 1.27 correct responses out of
      5. Only 47.9% of patients knew the bone they fractured, and 18.5% knew their
      expected healing time. Of the patients, 66.4% knew the type of implanted
      fixation, and 45.2% knew their weight-bearing status. The patients (74.0%) knew
      their DVT prophylaxis medication(s). The mean score for patients in the group <=
      HS (high-school education or less) was 2.26, whereas the mean score for patients
      in the group > HS (more than high-school education) was 3.00 (P = 0.0009). The
      patients in the group > HS were 2.54 times more likely to know the bone they
      fractured (P = 0.01), 3.82 times more likely to know the recovery time (P =
      0.004), and 2.79 times more likely to know their DVT prophylaxis medication(s)
      than patients in the group <= HS. CONCLUSIONS: Orthopedic trauma patients
      demonstrated limited comprehension of their injuries, surgeries, and
      postoperative instructions. Patients with lower educational levels did
      significantly worse on the questionnaire than those with higher educational
      levels. The results of the study highlight a lack of comprehension within this
      patient population and suggest that an increased focus on patient communication
      by orthopedic providers may be necessary.

PMID- 23114415
TI  - Pain dominates summed scores for hindfoot and ankle trauma.
AB  - BACKGROUND: Outcomes in clinical orthopaedic research are often presented as a
      summed functional score, without the individual component scores. Thus, there is
      little information about the effect of each component score on the overall score
      in hindfoot and ankle trauma. The purpose of this study was to determine which
      subscores were most responsible for the overall variation in summed scores and to
      evaluate the correlation of multiple scoring systems after foot and ankle
      fractures or reconstruction. METHODS: One hundred fifty-eight patients were
      evaluated after open reduction internal fixation of the calcaneus, open reduction
      internal fixation of the plafond, or ankle fusion with the Short Form 36,
      American Orthopedic Foot and Ankle Society (AOFAS), and Maryland scoring systems.
      Correlations were made between summed scores using a Pearson correlation matrix
      and the percentage of overall variation of the summed score that is accounted for
      by the answer to the pain question within the score. RESULTS: For all 3 subsets
      of patients, there was strong statistical correlation of the Short Form 36
      physical component summary, AOFAS, and Maryland scores (P < 0.001). The strongest
      correlation was between the AOFAS and the Maryland scores for each subset:
      calcaneus (r = 0.957, P < 0.0001), pilon (r = 0.946, P < 0.0001), and ankle
      fusion (r = 0.944, P < 0.0001). The pain subscore accounted for almost the entire
      variation in the summed score, being responsible for 80% to 86% of the overall
      variation. There was minimal change in overall variation when physical
      examination was factored into the analysis. CONCLUSIONS: Pain dominates the
      variation in summed scores for hindfoot and ankle trauma and reconstruction. We
      strongly recommend that when summed scores are used that the individual
      components are reported.

PMID- 23114416
TI  - Does maximum torque mean optimal pullout strength of screws?
AB  - OBJECTIVES: To determine the relationship between insertion torque and pullout
      strength of 3.5-mm-diameter cortical screws in cadaveric humeri with different
      bone mineral densities (BMDs). METHODS: Five pairs of human humeri from each of 3
      BMD groups (normal, osteopenic, and osteoporotic) were used. Holes were drilled
      in each humerus, and maximum insertion torque (T(max)) was measured by tightening
      a screw until stripping occurred. In the remaining holes, screws were tightened
      to 50%, 70%, or 90% of the T(max). A servohydraulic testing machine pulled each
      screw out at 1 mm/s while resulting force and axial displacement were recorded at
      10 Hz. The authors checked for an effect of insertion torque (percent T(max)) on
      pullout strength using a general linearized and latent mixed model (Stata10),
      controlling for cortical thickness and BMD (T-score). RESULTS: Pullout strength
      for normal and osteoporotic bone was greatest for screws inserted to 50% T(max)
      and was significantly greater than that at T(max) but not significantly different
      from that at 70% or 90% T(max). For osteopenic bone, pullout strength was
      greatest at 70% peak torque, but it was not significantly different from the
      pullout strength at the 50% or 90% T(max) levels. CONCLUSIONS: Tightening screws
      beyond 50% T(max) does not increase pullout strength of the screw and may place
      bone at risk for damage that might result in loss of fixation. Even after
      adjusting for bone thickness and density, there is no clear relationship between
      pullout strength and screw torque.

PMID- 23114417
TI  - Injury severity score underpredicts injury severity and resource utilization in
      combat-related amputations.
AB  - OBJECTIVE: Assess effectiveness of Injury Severity Score (ISS) in predicting
      injury severity in combat-related amputations. DESIGN: Retrospective evaluation
      of prospectively collected data. SETTING: Military medical center. PATIENTS: One
      hundred and nine patients with major extremity amputations sustained in overseas
      combat. INTERVENTION: Standard combat casualty care. MAIN OUTCOME MEASUREMENTS:
      Difference in injury severity as measured by ISS, numbers of extremity(s)
      amputated, number of associated injuries, blood products used, intensive care
      unit length of stay, hospital length of stay in those with an upper extremity
      amputation (UEA) compared with those with an isolated lower extremity amputation.
      RESULTS: Thirteen patients (11.9%) sustained at least one UEA. Patients with an
      UEA had a greater number of amputations per casualty compared with patients with
      a lower extremity alone (2.5 vs. 1.5; P < 0.001). The mean hospital length of
      stay (P = 0.02) and intensive care unit length of stay (P = 0.02) were
      significantly greater in those with an UEA. Mean blood product utilization was
      also significantly greater in those with an upper extremity amputation (P <
      0.05). There was no difference in ISS between the two groups (P > 0.05).
      CONCLUSIONS: The presence of an UEA is associated with increased injury severity
      as evident by increased intensive care unit requirements, blood product
      utilization, and hospital length of stay. ISS underestimates the severity of
      injury and therefore resource utilization in patients with multiple combat
      related amputations. Recognition of this limitation in addition to the
      development of a military-specific ISS is required for more effective resource
      utilization to continue to improve combat casualty care. LEVEL OF EVIDENCE:
      Prognostic Level II. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 23114418
TI  - Biomechanical comparison of standard iliosacral screw fixation to transsacral
      locked screw fixation in a type C zone II pelvic fracture model.
AB  - OBJECTIVES: Iliosacral screw fixation into the first sacral body is a common
      method for pelvic ring fixation. However, this construct has been shown to be
      clinically unreliable for the percutaneous fixation of unstable Type C zone II
      vertically oriented sacral fractures with residual fracture site separation. The
      objective of this study was to biomechanically compare a locked transsacral
      construct versus the standard iliosacral construct in a Type C zone II sacral
      fracture model. METHODS: A Type C pelvic ring injury was created in ten embalmed
      cadaver pelves by performing vertical osteotomies through zone II of the sacrum
      and the ipsilateral pubic rami. The sacrum was then reduced maintaining a 2 mm
      fracture gap. Five specimens were fixed using two 7.0-mm iliosacral screws into
      the S1 body; the other 5 were fixed using one 7.0-mm iliosacral screw and one 7.0
      mm transsacral screw exiting the contralateral ilium with a nut placed on its
      end, creating a locked construct. Each pelvis underwent 100,000 cycles at 250 N
      and was then loaded to failure using a unilateral stance testing model. Vertical
      displacements at 25,000; 50,000; 75,000 and 100,000 cycles and failure force were
      recorded for each pelvis. RESULTS: The locked transsacral construct performed
      significantly better than the iliosacral construct at all 4 measurement points (P
      = 0.009) and in force to failure (P value = 0.02). CONCLUSIONS: Fixation of
      unstable zone II sacral fractures using the combination of an iliosacral screw
      and a locked transsacral screw resists deformation and withstands a greater force
      to failure as compared to fixation with 2 standard iliosacral screws. This locked
      transsacral construct may prove advantageous, especially when a percutaneous
      technique is used for a Type C zone II vertically oriented sacral fracture injury
      pattern, which can result in residual fracture site separation.

PMID- 23114419
TI  - Rotationally stable screw-anchor versus sliding hip screw plate systems in stable
      trochanteric femur fractures: a biomechanical evaluation.
AB  - OBJECTIVES: The rotationally stable screw-anchor plate system (RoSA) is unique in
      using a novel screw-blade combination. This investigation tested the hypothesis
      whether RoSA is advantageous over the sliding hip screw plate system (SHS) with
      regard to stiffness, failure load, displacement, and migration in stable
      trochanteric femur fractures (OTA 31A1.1). METHODS: Thirteen femur pairs (mean
      age = 79 years; range, 64-92 years) received implants of either the RoSA or SHS
      (Koenigsee Implants, Allendorf, Germany). Beginning with 300 N and under
      consecutive 300 N load-increase steps (2000 cycles, 0.5 Hz) the femurs were
      cycled until failure. Specimens were evaluated for fragment displacement in both
      frontal and rotational planes and for migration. A survival analysis was carried
      out. RESULTS: With regard to stiffness (526 +/- 195 N/mm vs 358 +/- 143 N/mm; P =
      0.006) and the failure load (2838 +/- 781 N vs 2262 +/- 863 N; P = 0.012), the
      RoSA proved superior to the SHS. Furthermore, RoSA demonstrated higher rotational
      stability in comparison to the SHS (1800 N: 0 +/- 0 degrees vs 1.1 +/- 1.3
      degrees; P = 0.015; failure point: 0 +/- 0 degrees vs 2.3 +/- 2.6 degrees; P =
      0.008), measuring rotation about femoral neck axis over time. Whereas cutout
      occurred only in the RoSA system (n = 3; P = 0.110), the SHS underwent plastic
      deformation in 7 cases (n = 7; P = 0.003). In one case (7%), the insertion of the
      RoSA blade resulted in iatrogenic cut-through caused by a jamming of the screw
      and the blade. CONCLUSIONS: The fixation of stable trochanteric femur fractures
      with RoSA in cadavers led to greater primary stability under cyclic load, with
      significant advantages with regard to stiffness, failure load, and rotational
      stability, compared with the SHS. A detrimental effect was its migration
      tendency, which began at 1800 N and occurred in the cranial direction. A
      meticulous insertion technique was a prerequisite to avoid iatrogenic perforation
      of the femoral head. Our results will have to be substantiated by further
      biomechanical and clinical trials using an optimized RoSA system.

PMID- 23114420
TI  - Theoretical and computational studies of dendrimers as delivery vectors.
AB  - It is a great challenge for nanomedicine to develop novel dendrimers with maximum
      therapeutic potential and minimum side-effects for drug and gene delivery. As
      delivery vectors, dendrimers must overcome lots of barriers before delivering the
      bio-agents to the target in the cell. Extensive experimental investigations have
      been carried out to elucidate the physical and chemical properties of dendrimers
      and explore their behaviors when interacting with biomolecules, such as gene
      materials, proteins, and lipid membranes. As a supplement of the experimental
      techniques, it has been proved that computer simulations could facilitate the
      progress in understanding the delivery process of bioactive molecules. The
      structures of dendrimers in dilute solutions have been intensively investigated
      by monomer-resolved simulations, coarse-grained simulations, and atom-resolved
      simulations. Atomistic simulations have manifested that the hydrophobic
      interactions, hydrogen-bond interactions, and electrostatic attraction play
      critical roles in the formation of dendrimer-drug complexes. Multiscale
      simulations and statistical field theories have uncovered some physical
      mechanisms involved in the dendrimer-based gene delivery systems. This review
      will focus on the current status and perspective of theoretical and computational
      contributions in this field in recent years. (275 references).

PMID- 23114421
TI  - Hydrodynamic interactions between colloidal particles in a planar pore.
AB  - The correlation between the motion of pairs of colloidal particles confined in a
      planar pore is measured using optical microscopy. The systems studied here are
      aqueous suspensions of polystyrene spheres of diameter 1.9 MUm, interacting as
      effective hard spheres, confined between two parallel planar plates separated by
      2.9 MUm. The lateral motion, along the plane parallel to the plates, of the
      particles is recorded with a time resolution of 30 frames s(-1). From the short
      time motion, the hydrodynamic diffusion coefficients are determined as functions
      of the interparticle distance for various particle concentrations. At low
      concentrations, when the static correlation between particles is also low, the
      diffusion coefficients exhibit some symmetry, and at higher concentrations they
      are modulated by the structure of static correlation.

PMID- 23114422
TI  - Lung nodule detected by F-18 fluorodeoxyglucose positron emission tomography
      computed tomography in patients with papillary thyroid cancer, negative 131I
      whole body scan, and undetectable serum-stimulated thyroglobulin levels: two case
      reports.
AB  - INTRODUCTION: When a pulmonary nodular lesion is detected by F-18
      fluorodeoxyglucose positron emission tomography-computed tomography in a patient
      with post-surgical papillary thyroid carcinoma with undetectable serum-stimulated
      thyroglobulin levels and negative 131I whole body scan, diagnosis and management
      of the nodule may be confusing. CASE PRESENTATION: We describe two post-surgical
      patients with papillary thyroid carcinoma who showed pulmonary nodular lesions
      detected by F-18 fluorodeoxyglucose positron emission tomography-computed
      tomography. In both cases serum-stimulated thyroglobulin levels were undetectable
      and nodular lesions were not detected by 131I whole body scan. In the first case,
      a 64-year-old Asian woman showed one focal increased fluorodeoxyglucose uptake
      lesion in the right lower lobe of one of her lungs. Based on the histologic
      study, the pulmonary nodular lesion was diagnosed as a solitary pulmonary
      metastasis from papillary thyroid carcinoma. In the second case, a 59-year-old
      Asian woman showed a new pulmonary nodule in the right lower lobe. The computed
      tomography scan of her chest revealed a 9mm nodule in the anterior basal segment
      and another tiny nodule in the posterior basal segment of the right lower lobe.
      Six months later, both nodules had increased in size and miliary disseminated
      nodules were also seen in both lungs. Based on their histology, the pulmonary
      nodular lesions were considered to be primary lung adenocarcinoma. CONCLUSIONS:
      The present cases emphasize that physicians should be cautious and make efforts
      for an accurate diagnosis of pulmonary nodules detected on F-18
      fluorodeoxyglucose positron emission tomography-computed tomography in patients
      with papillary thyroid carcinoma with no evidence of metastasis such as negative
      131I whole body scan and undetectable stimulated serum thyroglobulin levels.

PMID- 23114423
TI  - Designer labels for plant metabolism: statistical design of isotope labeling
      experiments for improved quantification of flux in complex plant metabolic
      networks.
AB  - Metabolic fluxes are powerful indicators of cell physiology and can be estimated
      by isotope-assisted metabolic flux analysis (MFA). The complexity of the
      compartmented metabolic networks of plants has constrained the application of
      isotope-assisted MFA to them, principally because of poor identifiability of
      fluxes from the measured isotope labeling patterns. However, flux identifiability
      can be significantly improved by a priori design of isotope labeling experiments
      (ILEs). This computational design involves evaluating the effect of different
      isotope label and isotopomer measurement combinations on flux identifiability,
      and thereby identifying optimal labels and measurements toward evaluating the
      fluxes of interest with the highest confidence. This article reports ILE designs
      for two major, compartmented plant metabolic pathways - the pentose phosphate
      pathway (PPP) and gamma-aminobutyric acid (GABA) shunt. Together, these pathways
      represent common motifs in plant metabolism including duplication of pathways in
      different subcellular compartments, reversible reactions and cyclic carbon flow.
      To compare various ILE designs, we employed statistical A- and D-optimality
      criteria. Our computations showed that 1,2-(13)C Glc is a powerful and robust
      label for the plant PPPs, given currently popular isotopomer measurement
      techniques (single quadrupole mass spectrometry [MS] and 2-D nuclear magnetic
      resonance [NMR]). Further analysis revealed that this label can estimate several
      PPP fluxes better than the popular label 1-(13)C Glc. Furthermore, the concurrent
      measurement of the isotopomers of hexose and pentose moieties synthesized
      exclusively in the cytosol or the plastid compartments (measurable through
      intracellular glucose or sucrose, starch, RNA ribose and histidine) considerably
      improves the identifiability of PPP fluxes in the individual compartments.
      Additionally, MS-derived isotopomer measurements outperform NMR-derived
      measurements in identifying PPP fluxes. The potency of 1,2-(13)C Glc can be
      improved substantially by combining it with other labels (e.g. 3-(13)C Glc, 1
      (13)C Glc and U-(13)C Glc) in parallel ILEs. For the GABA shunt, we calculated
      that 100% 2-(13)C Ala and 100% U-(13)C Gln constitute the best labels. We
      anticipate that the ILE designs presented in this article can enhance the quality
      of flux estimates in these two complex plant pathways. In the future, these ILE
      designs can be further improved by leveraging recent analytical and computational
      developments in isotope-assisted MFA.

PMID- 23114424
TI  - Taurine ameliorates hyperglycemia and dyslipidemia by reducing insulin resistance
      and leptin level in Otsuka Long-Evans Tokushima fatty (OLETF) rats with long-term
      diabetes.
AB  - This study aimed to determine whether taurine supplementation improves metabolic
      disturbances and diabetic complications in an animal model for type 2 diabetes.
      We investigated whether taurine has therapeutic effects on glucose metabolism,
      lipid metabolism, and diabetic complications in Otsuka Long- Evans Tokushima
      fatty (OLETF) rats with long-term duration of diabetes. Fourteen 50-week-old
      OLETF rats with chronic diabetes were fed a diet supplemented with taurine (2%)
      or a non-supplemented control diet for 12 weeks. Taurine reduced blood glucose
      levels over 12 weeks, and improved OGTT outcomes at 6 weeks after taurine
      supplementation, in OLETF rats. Taurine significantly reduced insulin resistance
      but did not improve beta-cell function or islet mass. After 12 weeks, taurine
      significantly decreased serum levels of lipids such as triglyceride, cholesterol,
      high density lipoprotein cholesterol, and low density lipoprotein cholesterol.
      Taurine significantly reduced serum leptin, but not adiponectin levels. However,
      taurine had no therapeutic effect on damaged tissues. Taurine ameliorated
      hyperglycemia and dyslipidemia, at least in part, by improving insulin
      sensitivity and leptin modulation in OLETF rats with long-term diabetes.
      Additional study is needed to investigate whether taurine has the same beneficial
      effects in human diabetic patients.

PMID- 23114426
TI  - Stochastic transport of particles across single barriers.
AB  - Transport phenomena of interacting particles are of high interest for many
      applications in biology and mesoscopic systems. Here we present measurements on
      colloidal particles, which are confined in narrow channels on a substrate and
      interact with a barrier, which impedes the motion along the channel. The
      substrate of the particle is tilted in order for the particles to be driven
      towards the barrier and, if the energy gained by the tilt is large enough,
      surpass the barrier by thermal activation. We therefore study the influence of
      this barrier as well as the influence of particle interaction on the particle
      transport through such systems. All experiments are supported with Brownian
      dynamics simulations in order to complement the experiments with tests of a large
      range of parameter space which cannot be accessed in experiments.

PMID- 23114425
TI  - IL-17-deficient allogeneic bone marrow transplantation prevents the induction of
      collagen-induced arthritis in DBA/1J mice.
AB  - IL-17-producing CD4+ T cells (Th17) play important functions in autoimmune
      diseases and allograft rejection of solid organs. We examined the effects of IL
      17 and its mechanism of action on arthritis in a murine collagen-induced
      arthritis (CIA) model using bone marrow transplantation (BMT) system. DBA/1J mice
      were administered a lethal radiation dose and then rescued with bone marrow
      derived from either wild-type (WT) or IL-17-/- mice on C57BL/6 background mice.
      CIA was induced after the bone marrow transplant, and disease progression was
      characterized. DBA/1J mice with CIA that received IL-17-/- donor bone marrow
      showed potently inhibited development and severity of clinical arthritis as
      compared with CIA mice that received WT bone marrow. Reduced secretion of the pro
      inflammatory cytokines tumor necrosis factor-alpha, IL-1beta, and IL-6, and
      collagen-specific T cell responses were observed in mice that received IL-17-/-
      bone marrow. IL-17 blockade also inhibited effector T cell proliferation by
      reciprocally regulating the Treg/Th17 ratio. IL-17 blockade prevented joint
      destruction in mice with CIA. These findings suggest that CIA with BMT is a
      viable method of immunological manipulation and that IL-17 deficiency suppresses
      severe joint destruction and inflammation in CIA mice. There may be clinical
      benefits in blocking IL-17 and BMT in the treatment of rheumatoid arthritis.

PMID- 23114427
TI  - Whole-canopy carbon gain as a result of selection on individual performance of
      ten genotypes of a clonal plant.
AB  - Game theoretical models predict that plant competition for light leads to reduced
      productivity of vegetation stands through selection for traits that maximize
      carbon gains of individuals. Using empirical results from a 5-year competition
      experiment with 10 genotypes of the clonal plant Potentilla reptans, we tested
      this prediction by analyzing the effects of the existing leaf area values on the
      carbon gain of the different genotypes and the consequent whole canopy carbon
      gain. We focused on specific leaf area (SLA) due to its role in the trade-off
      between light capture area and photosynthetic capacity per unit area. By
      combining a canopy model based on measured leaf area and light profiles with a
      game theoretical approach, we analyzed how changes in the SLA affected genotypic
      and whole-stand carbon gain. This showed that all genotypes contributed to
      reduced stand productivity. The dominant genotype maximized its share of total
      carbon gain, resulting in lower than maximal absolute gain. Other genotypes did
      not maximize their share. Hypothetical mutants of the dominant genotype were not
      able to achieve a higher carbon gain. Conversely, in other genotypes, some
      mutations did result in increased carbon gain. Hence, genotypic differences in
      the ability to maximize performance may determine genotype frequency. It shows
      how genotypic selection may result in lower carbon gains of the whole vegetation,
      and of the individual genotypes it consists of, through similar mechanisms as
      those that lead to the tragedy of the commons.

PMID- 23114428
TI  - Mass-flowering crops enhance wild bee abundance.
AB  - Although agricultural habitats can provide enormous amounts of food resources for
      pollinator species, links between agricultural and (semi-)natural habitats
      through dispersal and foraging movements have hardly been studied. In 67 study
      sites, we assessed the interactions between mass-flowering oilseed rape fields
      and semi-natural grasslands at different spatial scales, and their effects on the
      number of brood cells of a solitary cavity-nesting bee. The probability that the
      bee Osmia bicornis colonized trap nests in oilseed rape fields increased from 12
      to 59 % when grassland was nearby, compared to fields isolated from grassland. In
      grasslands, the number of brood cells of O. bicornis in trap nests was 55 %
      higher when adjacent to oilseed rape compared to isolated grasslands. The
      percentage of oilseed rape pollen in the larval food was higher in oilseed rape
      fields and grasslands adjacent to oilseed rape than in isolated grasslands. In
      both oilseed rape fields and grasslands, the number of brood cells was positively
      correlated with the percentage of oilseed rape pollen in the larval food. We show
      that mass-flowering agricultural habitats--even when they are intensively managed
      -can strongly enhance the abundance of a solitary bee species nesting in nearby
      semi-natural habitats. Our results suggest that positive effects of agricultural
      habitats have been underestimated and might be very common (at least) for
      generalist species in landscapes consisting of a mixture of agricultural and semi
      natural habitats. These effects might also have--so far overlooked--implications
      for interspecific competition and mutualistic interactions in semi-natural
      habitats.

PMID- 23114429
TI  - Theoretical investigation on detonation performances and thermodynamic
      stabilities of the prismane derivatives.
AB  - Based on DFT-B3LYP/6-311G** method, the molecular geometric structures of
      polynitramineprismanes are fully optimized. The detonation performances, energy
      gaps, strain energies, as well as their stability were investigated to look for
      high energy density compounds (HEDCs). Our results show that all
      polynitramineprismanes have high and positive heat of formation. To construct the
      relationship between stabilities and structures, energy gaps and bond
      dissociation energies are calculated, and these results show that the energy gaps
      of prismane derivatives are much higher than that of TATB (0.1630). In addition,
      the C-C bonds on cage are confirmed as trigger bond in explosive reaction. All
      polynitramineprismanes have large strain energies, and the strain energies of all
      compounds are slightly smaller than prismane, which indicated that the strain
      energies were somewhat released compared to prismane. Considering the
      quantitative criteria of HEDCs, hexanitramineprismane is a good candidate of high
      energy compounds.

PMID- 23114430
TI  - Insight into the dynamic interaction between different flavonoids and bovine
      serum albumin using molecular dynamics simulations and free energy calculations.
AB  - In this study, the binding of Bovine serum albumin (BSA) with three flavonoids,
      kaempferol-3-O-a-L-rhamnopyranosyl-(1-3)-a-L-rhamnopyranosyl-(1-6)-b-D-galacto-
      pyranoside (drug 1),kaempfol-7-O-rhamnosyl-3-O-rutinoside (drug 2)andkaempferide
      7-O-(4"-O-acetylrhamnosyl)-3-O-ruti- noside (drug 3) is investigated by molecular
      docking, molecular dynamics (MD) simulation, and binding free energy calculation.
      The free energies are consistent with available experimental results and suggest
      that the binding site of BSA-drug1 is more stable than those of BSA-drug2 and BSA
      drug3. The energy decomposition analysis is performed and reveals that the
      electrostatic interactions play an important role in the stabilization of the
      binding site of BSA-drug1 while the van der Waals interactions contribute largely
      to stabilization of the binding site of BSA-drug2 and BSA-drug3. The key residues
      stabilizing the binding sites of BSA-drug1, BSA-drug2 and BSA-drug3 are
      identified based on the residue decomposition analysis.

PMID- 23114431
TI  - Simple benzene derivatives adsorption on defective single-walled carbon
      nanotubes: a first-principles van der Waals density functional study.
AB  - We have investigated the interaction between open-ended zig-zag single-walled
      carbon nanotube (SWCNT) and a few benzene derivatives using the first-principles
      van der Waals density functional (vdW-DF) method, involving full geometry
      optimization. Such sp (2)-like materials are typically investigated using
      conventional DFT methods, which significantly underestimate non-local dispersion
      forces (vdW interactions), therefore affecting interactions between respected
      molecules. Here, we considered the vdW forces for the interacting molecules that
      originate from the interacting pi electrons of the two systems. The -0.54 eV
      adsorption energy reveals that the interaction of benzene with the side wall of
      the SWCNT is typical of the strong physisorption and comparable with the
      experimental value for benzene adsorption onto the graphene sheet. It was found
      that aromatics are physisorbed on the sidewall of perfect SWCNTs, as well as at
      the edge site of the defective nanotube. Analysis of the electronic structures
      shows that no orbital hybridization between aromatics and nanotubes occurs in the
      adsorption process. The results are relevant in order to identify the potential
      applications of noncovalent functionalized systems.

PMID- 23114432
TI  - Interplay between halogen bonds and hydrogen bonds in OH/SH...HOX...HY (X = Cl,
      Br; Y = F, Cl, Br) complexes.
AB  - The character of the cooperativity between the HOX...OH/SH halogen bond (XB) and
      the Y-H...(H)OX hydrogen bond (HB) in OH/SH...HOX...HY (X = Cl, Br; Y = F, Cl,
      Br) complexes has been investigated by means of second-order Moller-Plesset
      perturbation theory (MP2) calculations and "quantum theory of atoms in molecules"
      (QTAIM) studies. The geometries of the complexes have been determined from the
      most negative electrostatic potentials (V (S,min)) and the most positive
      electrostatic potentials (V (S,max)) on the electron density contours of the
      individual species. The greater the V (S,max) values of HY, the larger the
      interaction energies of halogen-bonded HOX...OH/SH in the termolecular complexes,
      indicating that the ability of cooperative effect of hydrogen bond on halogen
      bond are determined by V (S,max) of HY. The interaction energies, binding
      distances, infrared vibrational frequencies, and electron densities rho at the
      BCPs of the hydrogen bonds and halogen bonds prove that there is positive
      cooperativity between these bonds. The potentiation of hydrogen bonds on halogen
      bonds is greater than that of halogen bonds on hydrogen bonds. QTAIM studies have
      shown that the halogen bonds and hydrogen bonds are closed-shell noncovalent
      interactions, and both have greater electrostatic character in the termolecular
      species compared with the bimolecular species.

PMID- 23114433
TI  - [Awareness, knowledge and responsibility].

PMID- 23114434
TI  - [Healthcare-associated infection rates: measuring and comparing. Experiences from
      the German National Nosocomial Infection Surveillance System (KISS) and from
      other surveillance systems].
AB  - Surveillance of nosocomial infections is meanwhile a cornerstone of infection
      prevention activities in hospitals. The objective of this article is to compare
      healthcare-associated infection rates in intensive care patients, neonatal
      intensive care patients and operated patients (ICU-KISS, OP-KISS, NEO-KISS) of
      the German nosocomial infection surveillance system (KISS) with the corresponding
      data of the US American National Healthcare Safety Network (NHSN) and the
      European Centre for Disease Prevention and Control (ECDC). In general, the
      methodological differences among the three surveillance systems are minor but
      there are some exceptions. Therefore, differences between countries have to be
      interpreted very carefully as they may be due to differences in diagnostics,
      patient mix, types of interventions, length of stay, selection of participating
      hospitals, post-discharge surveillance activities and interpretation of case
      definitions. Organizational aspects, such as mandatory participation with public
      disclosure on infection rates may also have an impact.

PMID- 23114435
TI  - [Antimicrobial resistance in Germany. Four years of antimicrobial resistance
      surveillance (ARS)].
AB  - In 2007, the Robert Koch Institute established the infrastructure for the
      national Antimicrobial Resistance Surveillance (ARS) system. Laboratories submit
      data of routine susceptibility testing of clinical samples from hospitals as well
      as from outpatient care settings in a standardized format to the Robert Koch
      Institute for central processing. The database for the period 2008-2011 comprises
      data of about 1.3 million samples from patients in hospital care and almost
      800,000 samples from outpatients. Based on SIR interpretations of susceptibility,
      the trends of methicillin resistance of Staphylococcus aureus (MRSA) and
      cefotaxime non-susceptibility as an indicator of extended-spectrum beta
      lactamases (ESBL) of Escherichia coli and Klebsiella pneumoniae were analyzed for
      four care settings or categories: hospital care, outpatient care, intensive care
      units, and isolates from blood cultures. After constant high levels of above 20%,
      the proportion of MRSA isolates showed a decline for the first time from 2010 to
      2011 in hospital care overall, in intensive care units as well as in blood
      cultures; in outpatient care, MRSA proportions of about 13% were observed. Within
      the observed period, non-susceptibility to cefotaxime as an indicator of ESBL in
      E. coli showed an increasing trend in hospital care at a level above 10% in
      intensive care units, while cefotaxime non-susceptibility in K. pneumoniae was
      more frequent but without any trend. In outpatient care, the proportions of
      cefotaxime non-susceptibility increased year by year in both species resulting in
      nearly a doubling to 6%.

PMID- 23114436
TI  - [Current data and trends on methicillin-resistant Staphylococcus aureus (MRSA)].
AB  - Nosocomial infections caused by methicillin-resistant Staphylococcus aureus
      (MRSA) are a problem in hospital settings worldwide. The National Reference
      Centre for Staphylococci performs molecular typing on a representative sample set
      of MRSA isolates from German hospitals for assessing long-term trends thus
      following the dynamics of emergence and spread of MRSA clones. The article
      focuses on recent data concerning antibiotic resistance and epidemic MRSA in
      nosocomial settings and also reflects the impact of community-acquired MRSA and
      MRSA from zoonotic reservoirs. Identifying common and newly emerging clones is an
      on-going challenge in the changing epidemiology of MRSA and prevention of further
      spread needs molecular surveillance.

PMID- 23114437
TI  - [Vancomycin-resistant enterococci (VRE). Recent results and trends in development
      of antibiotic resistance].
AB  - Enterococci (mainly E. faecalis, E. faecium) are important nosocomial pathogens
      predominantly affecting older and/or immunocompromised patients. The bacteria
      possess a broad spectrum of intrinsic and acquired antibiotic resistance
      properties. Among these, the transferrable glycopeptide resistance of the vanA
      and vanB genotypes in vancomycin-resistant enterococci (VRE; reservoir: E.
      faecium) as well as resistance to last resort antibiotics (e.g. linezolid and
      tigecycline) are of special concern. Enterococci (including VRE) are easily
      transferred in hospitals; however, colonizations are far more frequent than
      infections. Resistance frequencies for vancomycin in clinical E. faecium isolates
      have remained at a relatively constant level of 8-15% (but with local or regional
      variations) in recent years whereas frequencies for teicoplanin resistance have
      shown a slight decrease. Glycopeptide resistance trends correlate with a spread
      of hospital-associated E. faecium strains carrying the vanA and, with rising
      frequency in recent years, the vanB gene cluster, the latter being associated
      with teicoplanin susceptibility. This increased occurrence of vanB-positive E.
      faecium strains may be caused by an increased use of antibiotics selecting
      enterococci and VRE as well as due to methodological reasons (e.g. reduced EUCAST
      MIC-breakpoints for glycopeptides; increased use and sensitive performance of
      chromogenic VRE agars, increased use of molecular diagnostic assays).

PMID- 23114438
TI  - [Carbapenemases in gram-negative bacteria. Current data and trends of resistance
      resulting from the work of national reference centres].
AB  - The spread of carbapenemase-producing gram-negative bacteria is one of the major
      challenges of the present. Since 2009, the National Reference Laboratory for gram
      negative nosocomial pathogens has observed the molecular epidemiology of
      carbapenemases in Germany. In 2011, 1,454 referred bacterial isolates were tested
      for the presence of carbapenemases. Carbapenemase was found in 34.4% of
      Enterobacteriaceae isolates, in 19.9% of Pseudomonas aeruginosa isolates and in
      96.3% of Acinetobacter baumannii isolates. The most frequent carbapenemases in
      Enterobacteriaceae were OXA-48, KPC and VIM-1; in P. aeruginosa it was VIM-2 and
      in A. baumannii OXA-23.

PMID- 23114439
TI  - [Current data and trends about the resistance of Gram-negative pathogens to beta
      lactams].
AB  - In recent years the resistance of Gram-negative pathogens to beta-lactam
      antibiotics, such as cephalosporins and carbapenems has increased. The resistant
      strains produce different beta-lactam hydrolysing enzymes (beta-lactamases). In
      particular extended spectrum beta-lactamases (ESBL) are prevalent in Escherichia
      coli and Klebsiella pneumoniae. The ESBL genes are located on different plasmids
      facilitating the transfer of resistance within a species and between different
      Gram-negative species. Within the scope of various studies the Robert Koch
      Institute in Wernigerode investigated ESBL-producing human Enterobacteriaceae
      using molecular methods. The results showed that distinct ESBL types, such as the
      CTX-M enzymes are dominant in Germany whereby CTX-M-15 and CTX-M-1 are the most
      prevalent variants in E. coli and K. pneumoniae. The aim of ongoing
      investigations within the RESET network project is to investigate the
      dissemination pathways of ESBL-producing bacteria in different settings (e.g. in
      humans, animals and food).

PMID- 23114440
TI  - [Current data and trends on the development of antibiotic resistance of
      Clostridium difficile].
AB  - Clostridium difficile is the most common pathogen causing antibiotic-associated
      diarrhea. Antibiotic therapy also favors the development and the epidemic
      spreading of multiresistant strains. In this present retrospective study clinical
      isolates from the University of Saarland Medical Center and of other German
      isolate referring hospitals were characterized by genotyping and antibiotic
      resistance testing. The most prevalent strains were ribotypes 001 (18%), 014
      (16%) and 027 (15%). Sensitivity to metronidazole and vancomycin was demonstrated
      for 99.7 % of the clinical isolates independent of the genotype. Of the isolates
      96 % were rifampicin susceptible; however, significantly more cases of rifampicin
      resistance were found among 027 strains (12 %). Of the isolates 58% were
      clarithromycin sensitive and 57% moxifloxacin sensitive. In contrast to the
      various sporadic genotypes the majority of epidemic strains were macrolide or
      fluoroquinolone resistant (001, 027 and 078); however, discrimination between
      epidemic strains by antibiotic resistance profiles could not be discerned. A
      combination of consistent adherence to hygiene management guidelines and to a
      prudent and rational use of antimicrobials (antibiotic stewardship) may help to
      reduce the total number of C. difficile infections (CDI) and also the selection
      of multiresistant strains. On the other hand in the collection of isolates the
      sensitivity towards the standard oral antibiotic agents used for C. difficile
      treatment appears to be unimpaired by the global changes of C. difficile
      resistant profiles.

PMID- 23114441
TI  - [Rational antibiotic prescribing. Challenges and successes].
AB  - Rational and prudent antibiotic prescribing strategies are important both for the
      hospital sector as well as for ambulatory medicine. Prerequisites are the
      availability of antibiotic use and antibiotic resistance data and of
      infrastructure and trained personnel needed for implementing and evaluating
      antibiotic policies. Currently, these requirements are not being met sufficiently
      in Germany. A major challenge in this country is the lack of adequately trained
      and experienced personnel. On the other hand there are several projects and
      initiatives supported in part within the national antibiotic resistance control
      program which have produced some progress and success. One example is GERMAP, the
      national antibiotic use and resistance atlas covering both human medicine and the
      veterinary field. Other examples are the recently improved program for continuous
      hospital antibiotic use, surveillance and feedback and the Antibiotic Stewardship
      (ABS) training program with establishment of an ABS expert network. Future
      perspectives include programs for evaluation of practice guideline adherence and
      the development and evaluation of quality of care indicators. Intermediate and
      long-term investment is needed in specialty training and certification of a
      sufficient number of infectious disease physicians, medical microbiologists and
      infection control doctors/hospital epidemiologists and hospital pharmacists.

PMID- 23114442
TI  - [Adaptation and development of German recommendations on the prevention and
      control of nosocomial infections due to multiresistant pathogens].
AB  - The Commission for Hospital Hygiene and Infection Prevention at the Robert Koch
      Institute developed evidence-based recommendations for the prevention and control
      of nosocomial infections in Germany. Considering the growing impact of
      multiresistant pathogens (MRE) on morbidity and mortality related to nosocomial
      infections, the prevention and control of MRE is one of the most important topics
      on the current agenda. Currently, the German recommendations on methicillin
      resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus
      (VRE) are being re-evaluated and a recommendation discussing options for the
      prevention and control of MR Gram-negative pathogens is awaited and will be
      published in the next months.

PMID- 23114443
TI  - [Experiences with outbreaks of nosocomial infections].
AB  - Ten years after the publication of the recommendation: "Outbreak management and
      structural proceedings in case of cumulative occurrence of nosocomial infections"
      of the federal commission of hospital hygiene, these recommendations are now
      being re-evaluated. To date, the recommendations have proven valid and have
      maintained their significance for an effective management. However, besides new
      hygienic-microbiological methods and an increased sensitivity of the perception
      of nosocomial outbreaks by the public, by politicians and by the press, it is
      necessary to consider  new issues in this field. Outbreaks are tragic events
      placing an extraordinary burden on all persons involved, which can have
      significant consequences. Therefore, it is necessary to ensure prompt outbreak
      management by experienced professionals who must combine a systematic on-site
      inspection, hygienic-microbiological investigation and typing methods used with
      epidemiological approaches. To assure these requirements, the support of
      independent reference centres such as universal hygiene institutes should be
      guaranteed. Politicians should be involved only after a scientific  evaluation of
      the details of the outbreak has been made. A national documentation centre, e.g.
      at the Robert Koch Institute, should be established, thereby making experiences
      with outbreaks widely available.

PMID- 23114444
TI  - [The challenge of infections and multiresistant bacteria among the elderly living
      in long-term care facilities].
AB  - Healthcare-associated infections not only affect patients in acute care hospitals
      but also patients in need of long-term care. As the elderly are generally most
      affected, the demographic change in Germany faces a range of increasing
      challenges in the field of infection control. The ageing process itself is
      accompanied by several physiological and pathological changes which may result in
      an increase in the risk of infectious diseases. Elderly living in long-term care
      facilities (LTCFs) may in addition be exposed to further risks due to their
      everyday life in a community, nursing care and the, to some extent, inappropriate
      use of antibiotics. Bacteria that have become resistant to commonly used
      antimicrobial agents are meanwhile prevalent in nursing homes. Caregivers often
      feel left alone when facing the task of achieving a balance between the need for
      a comfortable familiar environment and the application of infection control
      measures according to a resolute prevention strategy. This review aims to give an
      overview about the characteristics of infections among the elderly, especially
      with respect to long-term care.

PMID- 23114445
TI  - [Methicillin-resistant Staphylococcus aureus (MRSA) in medical rehabilitation.
      Draft of a model hygiene plan].
AB  - Rehabilitation facilities often apply the same standards for management of
      methicillin-resistant Staphylococcus aureus (MRSA) carriers as acute care
      hospitals. This makes it difficult to ensure access to the facilities and
      adequate rehabilitation for carriers. A working group of the Bavarian state
      committee for multiresistant pathogens addressed these problems by a systematic
      review of literature, expert group meetings and evaluation of existing hygiene
      plans. Thereby a model hygiene plan for rehabilitation facilities concerning
      management of MRSA carriers was derived. The management is based on physician
      risk assessment blending standards applied in acute and long-term care
      facilities. For rehabilitation typical risk scenario examples of risk analyses
      are given. The preventive measures are based on the respective objectives of
      protection. The risk analysis which gives the basis for the model hygiene plan
      described in this paper gives equal weight to two main objectives of protection:
      infection control and medical rehabilitation.

PMID- 23114446
TI  - [Historical development and current demands on medical training, further and
      advanced training in hygiene and infection prevention].
AB  - New risks in nosocomial infections and the dramatic increase in antibiotic
      resistant pathogens in healthcare facilities have pointed to the urgent need for
      a good education of students and practitioners in the basics of hospital hygiene
      and infection prevention. On the other hand in the last 10 years a large number
      of institutes of hygiene in universities were closed with remarkable consequences
      concerning the decreased education in modern hygiene and public health. A broad
      historical overview over the last 200 years of teaching hygiene and public health
      at German universities is given which was integrated into the education of
      medical students. Nowadays many universities do not teach modern hygiene and
      public health. The demand of re-establishing new institutes of hygiene by the
      German Medical Council is discussed. The curriculum for the formation of hospital
      hygienists is presented.

PMID- 23114447
TI  - [Report of the third meeting of the coordinators of the regional MRP networks in
      Germany on 15 and 16 December 2011 at the Robert Koch Institute].
AB  - Since 2004 the Robert Koch-Institute has supported the formation of regional
      networks for prevention of the spread of methicillin-resistant Staphylococcus
      aureus and multiresistant pathogens (MRSA/MRP, EpiBull 5/2005)). The third
      meeting of the coordinators of the regional MRP networks in Germany took place on
      15 and 16 December 2011. A total of 60 representatives of the Public Health
      Services from 12 states participated. It must be emphasized that in the meantime
      many successfully established networks are active and not all coordinators of
      existing networks could participate merely due to the organizational format.
      Interested parties can obtain a good overview via a link to the corresponding
      internet homepage of each state under http://www.rki.de -> Infektionsschutz ->
      Krankenhaushygiene -> Regionale Netzwerke. In summary it was clear that the
      number and the activity of regional MRP networks in Germany have further
      increased. The networks can synergistically benefit from important experiences
      through the different individual focal points of each network and a corresponding
      exchange of ideas.

PMID- 23114448
TI  - [Hygiene in intensive care units in Frankfurt am Main, Germany].
AB  - : The German Commission on Hospital Hygiene and Infection Prevention has
      published several recommendations regarding hygiene in the intensive care unit.
      Compliance with these recommendations was surveyed. METHODS: In 2005 and 2011,
      the intensive care units of all hospitals in Frankfurt am Main, Germany, were
      examined by members of the public health department, using a checklist based on
      the respective recommendations. RESULTS: Recommendations on the architecture and
      function of intensive care wards were almost fully complied with, except for the
      stipulated amount of space and nursing personnel. Compliance with recommendations
      for prevention of ventilator-associated pneumonia and for prevention of catheter
      related bloodstream infections was excellent, with only some minor exceptions.
      Regarding hand hygiene, in 2011 fewer faults were documented than in 2005. All
      hospitals took part in the German project of the world-wide campaign "clean care
      is safer care." In 2005, device-associated infections were surveyed in 92%
      intensive care units, and in 2011 in all of them. By 2011, screening of
      methicillin-resistant Staphylococcus aureus had been established in all intensive
      care units. CONCLUSION: Most problems that were observed regarded a scarcity of
      space and of facilities for isolation of patients and of nursing personnel.
      Improvements were seen in hand hygiene and in screening for multidrug resistant
      organisms (MDRO).

PMID- 23114449
TI  - [Systematic assessment and improvement of medical data quality].
AB  - Public health research depends on empirical information that is based on data of
      high quality. The aim of this study was to apply the current guidelines developed
      by the Technology and Methodology Platform for Networked Medical Research (TMF)
      for the independent assessment and enhancement of data quality. A clinical
      register of female breast cancer patients from two periods (N = 389 of 1996-1997
      and N = 488 of 2003-2004) was used. To check the plausibility, organization, and
      correctness of the data quality levels, data quality indicators (DQI) were
      chosen, operationalized, and the variance ratios of normative-analytic-defined
      thresholds were calculated. Significant deviations led to data improvement, which
      included the commonly known source data verification (SDV). A summary data
      quality score was calculated before and after application of the guidelines.
      Eleven out of 24 DQIs were tested. Data quality systematically increased from
      51.6 to 67.7%. The guidelines facilitate a systematic assessment and improvement
      of data quality with a reasonable use of resources. This target-oriented
      procedure allows for a high transparency of the available data quality, which is
      essential for health research.

PMID- 23114450
TI  - [Early childhood caries and associated risk factors among infants in the German
      federal state of Brandenburg].
AB  - The objective of this study was to determine the caries experience in a
      representative sample of infants aged 13-36 months in the federal state of
      Brandenburg in relation to their parents' health behavior and social status.
      Calibrated public health service dentists examined 661 children in ten districts
      according to WHO standards (1997). Data on the parents' health behavior and their
      social status were acquired via questionnaire. The prevalence of caries was 7.4%
      on enamel-level (d1-4) and 5.3% on dentin-level (d3-4). The caries experience was
      0.3 d1-4mft/0.2 d3-4mft. Fifty-two percent of the total caries burden was
      concentrated on 2% of the children. The restorative index was 19.9% and the care
      index 10%, respectively. Children of 25-36 months of age and with a lower social
      status and those who were bottle-fed at night revealed a significantly higher
      caries risk (OR 3.84, p = 0.005; OR 7.34, p < 0.0001; OR 2.4, p = 0.022) compared
      to younger children, children with a higher social status, or those without
      nocturnal bottle use. Intersectoral prevention programs in day-care centers are
      the favored preventive approach to compensate the socially determined health
      inequality. The low care index needs to be communicated with the dental
      association to improve the accessibility of infants in dental practice.

PMID- 23114451
TI  - [The historical development of immunization in Germany. From compulsory smallpox
      vaccination to a National Action Plan on Immunization].
AB  - In the German Reich, smallpox vaccinations were organized by the state. A
      mandatory vaccination throughout the empire was introduced in 1874, which was
      continued in the Federal Republic of Germany (FRG) and the German Democratic
      Republic (GDR) until 1982/1983. From 1935, health departments were responsible
      for vaccinations. In the GDR, immunization was tightly organized: The state made
      great efforts to achieve high vaccination rates. Responsibilities were clearly
      defined at all levels and for all ages. While vaccination was initially mandatory
      only at the regional level, the legally mandated immunization schedule later
      contained compulsory vaccinations, e.g., against measles. In the beginning there
      were mandatory vaccinations in the FRG at the Lander level. Since 1961, the
      Federal Epidemics Act has impeded obligatory vaccinations. Instead, voluntary
      vaccinations based on recommendations were stressed. Since the 1980s,
      vaccinations have been shifted from the public health service sector to office
      based physicians. Today, public health authorities offer mainly supplementary
      vaccinations. In 2007, protective immunizations were introduced as compulsory
      benefits of the statutory health insurance (SHI). Recently, the German federal
      states developed a National Vaccination Plan to support immunization strategies.

PMID- 23114452
TI  - [Patient participation in medical decision making within an integrated health
      care system in Germany: results of a controlled cohort study].
AB  - An integrated health care project called "Gesundes Kinzigtal" was conducted in a
      rural area in Germany. As part of the project, physicians were trained  and other
      measures were taken to enhance patient involvement in medical decision making. As
      part of the external evaluation, various effects regarding patient involvement in
      medical decision making, patient involvement and information preference, decision
      confidence, patient satisfaction with ambulatory care and patient quality of life
      were examined. The data were gathered by means of a questionnaire on an annual
      basis between 2007 and 2009. Effects were compared between patients who were
      participating in the integrated care project and two control groups. Analyses are
      based on the data of 1,205 patients. Over time all outcomes decreased slightly,
      except for information preference and physical quality of life. No statistically
      significant intervention effects on patient involvement in medical decision
      making or any other outcome variable could be found. The intensity of the
      training was presumably too low to establish an enduring change in the physician
      patient interaction.

PMID- 23114453
TI  - [Progress report of the central ethics committee for stem cell research].

PMID- 23114454
TI  - [Updated procedural rules of the Committee of virus Disinfection of the German
      Association for the Control of Virus Diseases e.V. (DVV) for certification of
      disinfectants].

PMID- 23114456
TI  - Recent advances in cardanol chemistry in a nutshell: from a nut to nanomaterials.
AB  - This tutorial review could serve as an introduction of cardanol into the world of
      soft nanomaterials; it is a biobased lipid-mixture obtained from the plant
      Anacardium occidentale L. Cardanol is a renewable raw material derived from a
      byproduct of cashew nut processing industry: Cashew Nut Shell Liquid (CNSL).
      Cardanol is a rich mixture of non-isoprenoic phenolic compounds that is a
      valuable raw material for generating a variety of soft nanomaterials such as
      nanotubes, nanofibers, gels and surfactants. These nanostructures may then serve
      as templates for the synthesis of additional nanomaterials. The wealth and
      diversity of cardanol-derived functional nanomaterials has urged us to present an
      article that will give readers a taste of a new class of cardanol-derived
      functional amphiphiles, along with their ability to generate hierarchical
      functional nanomaterials through non-covalent soft-chemical routes. In this
      concise review, we discuss selected examples of novel biobased surfactants,
      glycolipids, and polymers derived from cardanol, and their subsequent self
      assembly into functional soft materials.

PMID- 23114457
TI  - Contribution of prolonged-release melatonin and anti-benzodiazepine campaigns to
      the reduction of benzodiazepine and Z-drugs consumption in nine European
      countries.
AB  - BACKGROUND: Benzodiazepines (BZD) and benzodiazepine receptor agonists (zolpidem,
      zaleplon, zopiclone, altogether Z-drugs) are most commonly prescribed for the
      treatment of insomnia. However, long-term use of BZD/Z-drugs is associated with
      major adverse events including, but not limited to, falls and fractures, domestic
      and traffic accidents, confusion, cognitive impairment, Alzheimer's disease and
      cancer. The prolonged use of these drugs is thought to be related to severe
      withdrawal symptoms and potential dependency. The chronic and extensive use of
      BZD/Z drugs has become a public health issue and has led to multiple campaigns to
      reduce both prescription and consumption of BZD/Z-drugs. Prolonged-release (PR)
      melatonin is the first of a new class of melatonin receptor agonist drugs that
      has demonstrated clinically relevant efficacy on improving quality of sleep and
      morning alertness, with a good safety profile. OBJECTIVE: This study aimed to
      analyze and evaluate the impact of anti-BZD/Z-drugs campaigns and the
      availability of alternative pharmacotherapy (PR-melatonin) on the consumption of
      BZD and Z-drugs in several European countries. METHODS: Annual sales data from
      nine European countries were extracted from the IMS sales database and analyzed
      to determine whether trends in use of these treatment options were attributed to
      campaigns and/or availability and affordability of safer alternatives on the
      market. RESULTS: Campaigns aiming to reduce the use of BZD/Z-drugs failed when
      they were not associated with the availability and market uptake of PR-melatonin.
      The reimbursement of PR-melatonin supports better penetration rates and a higher
      reduction in sales for BZD/Z-drugs.

PMID- 23114458
TI  - What's not to LIC?

PMID- 23114459
TI  - Response to R. Ellaway.

PMID- 23114460
TI  - Paediatric lipoblastoma in the head and neck: three cases and review of
      literature.
AB  - Lipoblastoma is a rare benign tumour arising from embryonic white fat. The
      tumours occur primarily in infancy and early childhood and usually arise from the
      limbs and the trunk, but neck involvement is rare. We report three cases of head
      and neck lipoblastoma. In all cases, imaging showed a well-delineated, fat
      containing tumour. After surgical resection, the outcome of these patients was
      uneventful.

PMID- 23114461
TI  - Efficacy of Nintendo Wii training on mechanical leg muscle function and postural
      balance in community-dwelling older adults: a randomized controlled trial.
AB  - BACKGROUND: Older adults show increased risk of falling and major risk factors
      include impaired lower extremity muscle strength and postural balance. However,
      the potential positive effect of biofeedback-based Nintendo Wii training on
      muscle strength and postural balance in older adults is unknown. METHODS: This
      randomized controlled trial examined postural balance and muscle strength in
      community-dwelling older adults (75+/-6 years) pre- and post-10 weeks of
      biofeedback-based Nintendo Wii training (WII, n = 28) or daily use of ethylene
      vinyl acetate copolymer insoles (controls [CON], n = 30). Primary end points were
      maximal muscle strength (maximal voluntary contraction) and center of pressure
      velocity moment during bilateral static stance. RESULTS: Intention-to-treat
      analysis with adjustment for age, sex, and baseline level showed that the WII
      group had higher maximal voluntary contraction strength (18%) than the control
      group at follow up (between-group difference = 269 N, 95% CI = 122; 416, and p =
      .001). In contrast, the center of pressure velocity moment did not differ (1%)
      between WII and CON at follow-up (between-group difference = 0.23 mm(2)/s, 95% CI
      = -4.1; 4.6, and p = .92). For secondary end points, pre-to-post changes favoring
      the WII group were evident in the rate of force development (p = .03), Timed Up
      and Go test (p = .01), short Falls Efficacy Scale-International (p = .03), and 30
      second repeated Chair Stand Test (p = .01). Finally, participants rated the Wii
      training highly motivating at 5 and 10 weeks into the intervention. CONCLUSIONS:
      Biofeedback-based Wii training led to marked improvements in maximal leg muscle
      strength (maximal voluntary contraction; rate of force development) and overall
      functional performance in community-dwelling older adults. Unexpectedly, static
      bilateral postural balance remained unaltered with Wii training. The high level
      of participant motivation suggests that biofeedback-based Wii exercise may ensure
      a high degree of compliance to home- and/or community-based training in community
      dwelling older adults.

PMID- 23114463
TI  - Effect of boron addition on injection molded 316L stainless steel: mechanical,
      corrosion properties and in vitro bioactivity.
AB  - The research was investigated the effect of boron additions on sintering
      characteristics, mechanical, corrosion properties and biocompatibility of
      injection molded austenitic grade 316L stainless steel. Addition of boron is
      promoted to get high density of sintered 316L stainless steels. The amount of
      boron plays a role in determining the sintered microstructure and all properties.
      In this study, 316L stainless steel powders have been used with the elemental NiB
      powders. A feedstock containing 62.5 wt% powders loading was molded at different
      injection molded temperature. The binders were completely removed from molded
      components by solvent and thermal debinding at different temperature. The
      debinded samples were sintered at different temperature for 60 min. Mechanical
      property, microstructural characterization and electrochemical property of the
      sintered samples were performed using tensile testing, hardness, optical,
      scanning electron microscopy and electrochemical corrosion experiments. Sintered
      samples were immersed in a simulated body fluid (SBF) with elemental
      concentrations that were comparable to those of human blood plasma for a total
      period of 15 days. Both materials were implanted in fibroblast culture for
      biocompatibility evaluations were carried out. Results of study showed that
      sintered 316L and 316L with NiB addition samples exhibited high mechanical and
      corrosion properties in a physiological environment. Especially, 316L with NiB
      addition can be used in some bioapplications.

PMID- 23114462
TI  - Efficacy of whey protein supplementation on resistance exercise-induced changes
      in lean mass, muscle strength, and physical function in mobility-limited older
      adults.
AB  - BACKGROUND: Whey protein supplementation may augment resistance exercise-induced
      increases in muscle strength and mass. Further studies are required to determine
      whether this effect extends to mobility-limited older adults. The objectives of
      the study were to compare the effects of whey protein concentrate (WPC)
      supplementation to an isocaloric control on changes in whole-body lean mass, mid
      thigh muscle cross-sectional area, muscle strength, and stair-climbing
      performance in older mobility-limited adults in response to 6 months of
      resistance training (RT). METHODS: Eighty mobility-limited adults aged 70-85
      years were randomized to receive WPC (40g/day) or an isocaloric control for 6
      months. All participants also completed a progressive high-intensity RT
      intervention. Sample sizes were calculated based on the primary outcome of change
      in whole-body lean mass to give 80% power for a 0.05-level, two-sided test.
      RESULTS: Lean mass increased 1.3% and 0.6% in the WPC and control groups,
      respectively. Muscle cross-sectional area was increased 4.6% and 2.9% in the WPC
      and control groups, respectively, and muscle strength increased 16%-50% in WPC
      and control groups. Stair-climbing performance also improved in both groups.
      However, there were no statistically significant differences in the change in any
      of these variables between groups. CONCLUSIONS: These data suggest that WPC
      supplementation at this dose does not offer additional benefit to the effects of
      RT in mobility-limited older adults.

PMID- 23114464
TI  - Application of the laser Doppler flowmeter for measurement of blood pressure and
      functional parameters of microcirculation.
AB  - The laser Doppler flowmeter has become an effective tool for the clinical study
      of microcirculation with non-invasive measurements and excellent velocity
      resolution. Microcirculation flow measurements cannot be used as reference
      criteria for circulation function. Thus, the relative change in fingertip
      microcirculation was measured through inflation and deflation of an automatic
      sphygmomanometer wrapped around the arm, and the blood pressure and functional
      parameters of circulation, such as biological zero (BZ), peak flow (PF) and time
      to peak flow (tp), were determined. For 50 healthy participants, the correlation
      coefficients for the laser Doppler flowmeter and oscillometric results were 0.950
      and 0.838 for systolic and diastolic pressure, respectively. The mean and
      standard errors for both methods fell within the range specified in the
      Association for the Advancement of Medical Instrumentation standards. The BZ of
      an edema patient was about 5 times higher than normal. For patients with
      peripheral arterial occlusive disease (PAOD), the PF could not be determined, and
      the tp was about twice the normal value. The accuracy of blood pressure
      measurements using the laser Doppler flowmeter was comparable to that of the
      commonly used oscillometric sphygmomanometer, and the physiological circulation
      functional parameters were useful in identifying signs of edema and PAOD.

PMID- 23114465
TI  - Integrated LTCC packaging for use in biomedical devices.
AB  - As implantable devices gain more widespread use, medical device manufacturers are
      constantly looking for novel materials that increase and improve capability and
      functionality. The packaging needs to be biocompatible, but it is also highly
      desirable for it to be radio transparent to facilitate wireless telemetry and
      remote powering. Low temperature co-fired ceramics (LTCC) provide a viable
      solution that meets these desired specifications while also having
      characteristics that support ease of manufacturing such as the ability for
      molding, shaping, and even embedding components within the material. In this
      work, inductor coils used for wireless telemetry and powering are integrated into
      the walls of the LTCC-based package to maximize the size of the passive component
      while optimizing the miniaturization of the implant. The package designed and
      fabricated in this work consisted of inductors approximating 20 mH with a quality
      factor of 7.8 at 2 MHz. When compared to similar devices in the literature the
      LTCC inductor out performed these devices when a power-link figure of merit is
      used for comparison.

PMID- 23114466
TI  - Effects of types and length of soft-segments on the physical properties and blood
      compatibility of polyurethanes.
AB  - Segmented polyurethane (SPU) materials based on different soft-segment component
      (PPG, PTMO and PBA) and various length of soft-segment (molecular weight of PBA:
      500, 700 and 1000) were synthesized in this research. The soft-segment components
      were synthesized from polyether-polyols (PPG and PTMO) or from polyester-polyol
      (PBA). The physical properties and structure characterization of the synthesized
      SPUs were fully investigated using differential scanning calorimetry (DSC)
      analysis, and stress-strain measurements. Blood compatibility was evaluated with
      the platelet adhesion ratio (PAR) and the morphological observation for adhering
      platelets. Our results showed that the physical properties and blood
      compatibility of SPUs were closely related to its composition, which was
      controlled by (1) the types of the soft-segment component employed and (2) the
      length of soft segments. Polyether-polyol-based SPUs exhibited greater phase
      separations, poorer tensile strengths, and better blood compatibility, compared
      with polyester-polyol-based SPUs. SPUs with shorter soft-segment component
      exhibited greater phase mixing, higher tensile strength, but lower blood
      compatibility of SPUs, as compared with its counterparts with longer soft-segment
      component.

PMID- 23114467
TI  - Effect of sandblasting on the mechanical properties of Y-TZP zirconia.
AB  - Surface modification techniques affect phase transformation which in turn
      influences strength of zirconia biomaterial. The study aimed at evaluating the
      tetragonal to monoclinic (t-m) phase transition of zirconia occurring after
      sandblasting three different ceramic abrasive materials and its subsequent effect
      on the strength. Zirconia bars (n=24) were sandblasted using silicon carbide
      (SiC), alumina (Al2O3) and zirconia (ZrO2) particles. After surface
      characterization by a scanning electron microscope (SEM) and a laser
      profilometer, the relative amount of transformed monoclinic (m) phase was
      analyzed by X-ray diffractometry (XRD) and its corresponding effect on the
      flexural strength and fatigue strength were determined. Data were analyzed using
      one-way analysis of variance ANOVA (p<0.05). Furthermore, Weibull statistics was
      used to analyze the variability of flexural strength. The highest amount of
      monoclinic content was found after sandblasting with SiC consequently resulting
      in an increased flexural strength and fracture resistance under cyclic load
      conditions. Weibull modulus was reduced in all the groups with SiC blasting
      showing the least degradation of m values. The strengthening mechanism that is
      attributed to sandblasting procedure is influenced by the abrasive material used.

PMID- 23114470
TI  - Malakoplakia masquerading as ulcerative colitis in an immunocompetent child.

PMID- 23114471
TI  - Long-term outcomes after surgery on pediatric patients with Crohn disease.
AB  - OBJECTIVE: Of pediatric patients with Crohn disease, 20% to 30% undergo surgery
      within 10 years. Although disease relapses and reoperations are common, long-term
      functional outcomes and quality of life (QoL) are unclear. METHODS: In 2010, we
      reviewed the hospital records of all pediatric patients with CD who had undergone
      intestinal resections during childhood in 2 major tertiary care hospitals between
      1985 and 2008 and mailed out questionnaires that asked about health outcomes and
      QoL. We compared the QoL of the patients and a group of matched controls randomly
      chosen from the Population Register Centre. RESULTS: In total, 36 children had
      undergone bowel resection a median of 10 years earlier and had at least 2 years
      of follow-up. Disease activation (verified at endoscopy) requiring medical or
      surgical treatment occurred in 94% (median 1.8 years after primary resection). At
      least 1 surgical complication occurred in 77%, and 54% underwent re-resection.
      The patients reported a median stool frequency of 3 stools during the day and
      zero at night, with 33% being totally continent. Overall, 96% were completely or
      moderately satisfied with the outcome of the surgery. The QoL was comparable
      between the patients and controls, but school or work absences diminished the QoL
      of the patients. CONCLUSIONS: Surgery for pediatric-onset CD is risky even under
      expert care. Disease relapses and bowel re-resections are common during the first
      decade after primary surgery. In the long term, however, bowel function is
      acceptable and the QoL is comparable between patients and their peers.

PMID- 23114472
TI  - Diffuse esophageal spasm in children referred for manometry.
AB  - Diffuse esophageal spasm (DES) causes chest pain and/or dysphagia in adults. We
      reviewed charts of 278 subjects 0 to 18 years of age after esophageal manometry
      to describe the frequency and characteristics of DES in children. Patient
      diagnoses included normal motility (61%), nonspecific esophageal motility
      disorder (20%), DES (13%, n=36), and achalasia (4%). Of patients with DES, the
      most common chief complaint was food refusal in subjects younger than 5 years
      (14/24, 58%) and chest pain in subjects older than 5 years (4/12, 33%). Comorbid
      medical conditions, often multiple, existed in 33 subjects. DES should be
      considered when young children present with food refusal.

PMID- 23114473
TI  - Recurrent desmoids determine outcome in patients with Gardner syndrome: a cohort
      study of three generations of an APC mutation-positive family across 30 years.
AB  - PURPOSE: Screening of Gardner syndrome (GS) patients is tailored towards
      prevention of colorectal cancer (CRC). However, many patients suffer from desmoid
      tumors, which are challenging to treat due to invasive growth and local
      recurrence. The aims of our study were to determine the effectiveness of
      screening in GS and analyze outcome of desmoid tumors by treatment modality.
      METHODS: This was a cohort study of a family of 105 descendants with GS. All
      family members who agreed were screened by endoscopy, and colorectal resection
      was performed upon pending malignancy. Resectable desmoids were excised, whereas
      large tumors were treated by a combination of brachytherapy (BT) and radiotherapy
      (RT). Main outcome measures were the incidence of CRC and overall and disease
      specific mortality (ClinicalTrial.gov ID NCT01286662). RESULTS: Thirty-seven of
      105 family members have GS. Preventive colorectal resections were performed in 16
      patients (15 %), with one death due to gastric cancer. In four patients who
      denied screening endoscopy, invasive tumors of the colon (three patients) and
      stomach developed. Of 33 desmoid tumors, 10 (30 %) were located in the mesentery,
      17 (52 %) in the abdominal wall, and 6 (18 %) in extra-abdominal sites. Excision
      of 12 desmoids was performed in eight patients. Four desmoids were treated by BT
      and RT and showed full or partial remission. CONCLUSIONS: Provided adequate
      screening, good long-term control of colorectal tumors is achievable. However,
      desmoid tumors determine survival and quality of life in many patients. Our data
      suggest good local control using a combination of brachytherapy/radiotherapy in
      large desmoids unsuitable for surgical resection.

PMID- 23114474
TI  - Statin use is associated with a reduced incidence of colorectal adenomatous
      polyps.
AB  - BACKGROUND: Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) have
      been shown to have potentially useful anticancer effects against colorectal
      cancers in experimental studies, but clinical studies have shown inconsistent
      results on colorectal cancer incidence. Most colorectal cancers are believed to
      develop through the polyp-cancer sequence. We hypothesized that statins may
      protect against the development of adenomatous polyps, and this may contribute to
      the apparent cancer-protective effects. OBJECTIVE: This study aims to compare
      previous statin use in patients with newly diagnosed adenomatous polyps against a
      control group without polyps. METHOD: A case-control study involving 264 patients
      attending for diagnostic colonoscopy at the Norfolk and Norwich University
      Hospital was used. Polyp cases were age and sex matched against controls with
      normal colonoscopies. Structured patient interviews and clinical notes were used
      to ascertain drug and risk factor. Logistic regression was used to compare statin
      exposure and correct for confounding factors. RESULTS: There was a significant
      negative association between prior statin use and a diagnosis of adenomatous
      polyps [odds ratio (OR) = 0.40 (0.24-0.76)]. The association was significantly
      stronger with higher statin doses [>=40 mg simvastatin or equivalent; OR 0.33
      (0.10-0.53)] or longer duration of use [>5 years; OR 0.36 (0.10-0.67)]. Statin
      use was negatively associated with both high- and low-risk polyps. CONCLUSIONS:
      Statins may have a protective effect against the development of adenomatous
      polyps. The negative association between statin use and polyp incidence showed a
      significant dose and duration relationship.

PMID- 23114475
TI  - Infliximab versus cyclosporine as rescue therapy in acute severe steroid
      refractory ulcerative colitis: a systematic review and meta-analysis.
AB  - PURPOSE: Acute severe colitis affects 25 % of patients with ulcerative colitis
      (UC). Up to 30-40 % of these patients are resistant to intensive steroid therapy
      and therefore require rescue therapy to prevent emergent colectomy. Data
      comparing rescue therapy using infliximab and cyclosporine are limited and
      equivocal. This study evaluates the outcomes of UC patients receiving infliximab
      or cyclosporine as rescue therapy in acute severe steroid-refractory
      exacerbations. METHODS: Electronic databases (PubMed, EMBASE, and Cochrane
      database) were searched for studies directly comparing infliximab and
      cyclosporine in UC, and references of included studies were screened. Two
      independent reviewers identified relevant studies and extracted data. Meta
      analyses were performed using the random effect model. Outcome measures included
      3- and 12-month colectomy rates, adverse drug reactions, and postoperative
      complications. RESULTS: Six retrospective cohort studies describing 321 patients
      met the inclusion criteria. The meta-analysis did not show significant
      differences between infliximab and cyclosporine in the 3-month colectomy rate
      (odds ratio (OR) = 0.86, 95 % confidence interval (CI) = 0.31-2.41, p = 0.775),
      in the 12-month colectomy rate (OR = 0.60, 95 % CI = 0.19-1.89, p = 0.381), in
      adverse drug reactions (OR = 0.76, 95 % CI = 0.34-1.70, p = 0.508), and in
      postoperative complications (OR = 1.66, 95 % CI = 0.26-10.50, p = 0.591). Funnel
      plot revealed no publication bias. CONCLUSIONS: Infliximab and cyclosporine are
      comparable when used as rescue therapy in acute severe steroid-refractory UC.
      Randomized trials are required to further evaluate these agents.

PMID- 23114476
TI  - Robotic right colectomy for cancer with intracorporeal anastomosis: short-term
      outcomes from a single institution.
AB  - PURPOSE: Laparoscopic surgery for colon cancer has widely accepted as safe and
      effective. However, few studies report outcomes on robotic right colon resection
      with confectioning of the intracorporeal ileocolic anastomosis. This study aims
      to evaluate the feasibility and safety of robotic right colon resection with
      intracorporeal ileocolic anastomosis (RRCIA) in patients with cancer. METHODS:
      Data of consecutive series of 20 patients undergoing RRCIA between June 2011 and
      May 2012 at our institution were prospectively collected in order to evaluate
      surgical and oncological short-term outcomes. RESULTS: Seven males and 13 females
      were operated of RRCIA during the study period. Mean age is 66.7 years. The mean
      overall operative time was 327.5 min (255-485), and the robot time was 286 min
      (range 225-440 min). No conversion to open or laparoscopy occurred. The mean
      specimen length was 32.7 cm (range 26-44 cm), and the mean number of harvested
      lymph nodes was 17.6 (range 14-21). During the 30 postoperative days, only one
      complication occurred, consisting in an infection of surgical specimen extraction
      wound. CONCLUSION: The RRCIA is a feasible and safe for patients with right colon
      cancer, also in terms of intraoperative oncological outcomes.

PMID- 23114477
TI  - Baicalin and its emerging antineoplastic effects in systemic malignancies besides
      colorectal carcinomas.

PMID- 23114478
TI  - Fatal complications in fistulizing Crohn's disease: brain abscess and squamous
      cell carcinoma.

PMID- 23114479
TI  - Cyanative self-condensation of aromatic aldehydes promoted by VO(O(i)Pr)(3)-Lewis
      base as a cooperative catalyst.
AB  - Self-condensation of aromatic aldehydes with trimethylsilyl cyanide proceeded by
      the cooperative catalytic effect of VO(O(i)Pr)(3) and a Lewis base to give the
      corresponding O-acylated cyanohydrins. The reaction conversion and selectivity
      were strongly dependent on the solvent used, the Lewis base, and the presence of
      oxygen. All the nine kinds of aromatic aldehydes considered herein afforded the O
      acylated cyanohydrins with excellent selectivity under an O(2) atmosphere.

PMID- 23114481
TI  - Foreword for the 2012 Eastern Association for the Surgery of Trauma (EAST)
      practice management guidelines supplement.

PMID- 23114480
TI  - Effect of lipoxin A4 on myocardial ischemia reperfusion injury following cardiac
      arrest in a rabbit model.
AB  - In the present study, we investigated the effect of lipoxin A4 on myocardial
      ischemia-reperfusion injury (IRI) following cardiac arrest (CA) in a rabbit
      model. Lipoxin A4 is a metabolite of arachidonic acid in the eicosanoid, it is
      called "brake signal" for its anti-inflammatory activity. Some inflammatory
      factors (IL-1beta, IL-6, TNF-alpha, and IL-10), NF-kappaB p65, infarct ratios,
      apoptotic index, cardiac troponin I (cTnI), hemodynamic and myocardial structures
      were measured or observed in different groups. Lipoxin A4 inhibits the expression
      of IL-1beta, IL-6, and TNF-alpha, the values of the infarct ratios, apoptotic
      index, the level of serum cTnI and NF-kappaB p65. Meanwhile, it improves the
      expression of IL-10, hemodynamic, myocardial structure, and function. These
      indicate that lipoxin A4 mitigates postresuscitation myocardial IRI in which anti
      inflammation and suppression of NF-kappaB activation may play an important role.

PMID- 23114482
TI  - The Eastern Association of the Surgery of Trauma approach to practice management
      guideline development using Grading of Recommendations, Assessment, Development,
      and Evaluation (GRADE) methodology.
AB  - The Eastern Association for the Surgery of Trauma (EAST) is a leader in evidence
      based medicine and the development of practice management guidelines (PMGs) in
      trauma and acute care surgery. The previous primer describing EAST's approach for
      assessing the quality of available evidence and making recommendations for
      developing PMGs was published in 2000. Since that time, many new systems have
      been developed in an attempt to overcome previous shortcomings and to devise a
      methodologically rigorous and transparent approach to the assessment of quality
      of evidence and development of guidelines. One of these is the Grading of
      Recommendations, Assessment, Development, and Evaluation (GRADE) system. The
      membership of EAST has determined that the GRADE methodology will be the system
      used in all future EAST PMGs. The purpose of this article was thus to describe
      the GRADE methodology.

PMID- 23114484
TI  - Selective nonoperative management of blunt splenic injury: an Eastern Association
      for the Surgery of Trauma practice management guideline.
AB  - BACKGROUND: During the last century, the management of blunt force trauma to the
      spleen has changed from observation and expectant management in the early part of
      the 1900s to mainly operative intervention, to the current practice of selective
      operative and nonoperative management. These issues were first addressed by the
      Eastern Association for the Surgery of Trauma (EAST) in the Practice Management
      Guidelines for Non-operative Management of Blunt Injury to the Liver and Spleen
      published online in 2003. Since that time, a large volume of literature on these
      topics has been published requiring a reevaluation of the current EAST guideline.
      METHODS: The National Library of Medicine and the National Institute of Health
      MEDLINE database was searched using Pub Med (www.pubmed.gov). The search was
      designed to identify English-language citations published after 1996 (the last
      year included in the previous guideline) using the keywords splenic injury and
      blunt abdominal trauma. RESULTS: One hundred seventy-six articles were reviewed,
      of which 125 were used to create the current practice management guideline for
      the selective nonoperative management of blunt splenic injury. CONCLUSION: There
      has been a plethora of literature regarding nonoperative management of blunt
      splenic injuries published since the original EAST practice management guideline
      was written. Nonoperative management of blunt splenic injuries is now the
      treatment modality of choice in hemodynamically stable patients, irrespective of
      the grade of injury, patient age, or the presence of associated injuries. Its use
      is associated with a low overall morbidity and mortality when applied to an
      appropriate patient population. Nonoperative management of blunt splenic injuries
      should only be considered in an environment that provides capabilities for
      monitoring, serial clinical evaluations, and has an operating room available for
      urgent laparotomy. Patients presenting with hemodynamic instability and
      peritonitis still warrant emergent operative intervention. Intravenous contrast
      enhanced computed tomographic scan is the diagnostic modality of choice for
      evaluating blunt splenic injuries. Repeat imaging should be guided by a patient's
      clinical status. Adjunctive therapies like angiography with embolization are
      increasingly important adjuncts to nonoperative management of splenic injuries.
      Despite the explosion of literature on this topic, many questions regarding
      nonoperative management of blunt splenic injuries remain without conclusive
      answers in the literature.

PMID- 23114483
TI  - Nonoperative management of blunt hepatic injury: an Eastern Association for the
      Surgery of Trauma practice management guideline.
AB  - BACKGROUND: During the last century, the management of blunt force trauma to the
      liver has changed from observation and expectant management in the early part of
      the 1900s to mainly operative intervention, to the current practice of selective
      operative and nonoperative management. These issues were first addressed by the
      Eastern Association for the Surgery of Trauma in the Practice Management
      Guidelines for Nonoperative Management of Blunt Injury to the Liver and Spleen
      published online in 2003. Since that time, a large volume of literature on these
      topics has been published requiring a reevaluation of the previous Eastern
      Association for the Surgery of Trauma guideline. METHODS: The National Library of
      Medicine and the National Institutes of Health MEDLINE database were searched
      using PubMed (http://www.pubmed.gov). The search was designed to identify English
      language citations published after 1996 (the last year included in the previous
      guideline) using the keywords liver injury and blunt abdominal trauma. RESULTS:
      One hundred seventy-six articles were reviewed, of which 94 were used to create
      the current practice management guideline for the selective nonoperative
      management of blunt hepatic injury. CONCLUSION: Most original hepatic guidelines
      remained valid and were incorporated into the greatly expanded current guidelines
      as appropriate. Nonoperative management of blunt hepatic injuries currently is
      the treatment modality of choice in hemodynamically stable patients, irrespective
      of the grade of injury or patient age. Nonoperative management of blunt hepatic
      injuries should only be considered in an environment that provides capabilities
      for monitoring, serial clinical evaluations, and an operating room available for
      urgent laparotomy. Patients presenting with hemodynamic instability and
      peritonitis still warrant emergent operative intervention. Intravenous contrast
      enhanced computed tomographic scan is the diagnostic modality of choice for
      evaluating blunt hepatic injuries. Repeated imaging should be guided by a
      patient's clinical status. Adjunctive therapies like angiography, percutaneous
      drainage, endoscopy/endoscopic retrograde cholangiopancreatography and
      laparoscopy remain important adjuncts to nonoperative management of hepatic
      injuries. Despite the explosion of literature on this topic, many questions
      regarding nonoperative management of blunt hepatic injuries remain without
      conclusive answers in the literature.

PMID- 23114485
TI  - Screening for blunt cardiac injury: an Eastern Association for the Surgery of
      Trauma practice management guideline.
AB  - BACKGROUND: Diagnosing blunt cardiac injury (BCI) can be difficult. Many patients
      with mechanism for BCI are admitted to the critical care setting based on
      associated injuries; however, debate surrounds those patients who are
      hemodynamically stable and do not otherwise require a higher level of care. To
      allow safe discharge home or admission to a nonmonitored setting, BCI should be
      definitively ruled out in those at risk. METHODS: This Eastern Association for
      the Surgery of Trauma (EAST) practice management guideline (PMG) updates the
      original from 1998. English-language citations were queried for BCI from March
      1997 through December 2011, using the PubMed Entrez interface. Of 599 articles
      identified, prospective or retrospective studies examining BCI were selected.
      Each article was reviewed by two members of the EAST BCI PMG workgroup. Data were
      collated, and a consensus was obtained for the recommendations. RESULTS: We
      identified 35 institutional studies evaluating the diagnosis of adult patients
      with suspected BCI. This PMG has 10 total recommendations, including two Level 2
      updates, two upgrades from Level 3 to Level 2, and three new recommendations.
      CONCLUSION: Electrocardiogram (ECG) alone is not sufficient to rule out BCI.
      Based on four studies showing that the addition of troponin I to ECG improved the
      negative predictive value to 100%, we recommend obtaining an admission ECG and
      troponin I from all patients in whom BCI is suspected. BCI can be ruled out only
      if both ECG result and troponin I level are normal, a significant change from the
      previous guideline. Patients with new ECG changes and/or elevated troponin I
      should be admitted for monitoring. Echocardiogram is not beneficial as a
      screening tool for BCI and should be reserved for patients with hypotension
      and/or arrhythmias. The presence of a sternal fracture alone does not predict
      BCI. Cardiac computed tomography or magnetic resonance imaging can be used to
      differentiate acute myocardial infarction from BCI in trauma patients.

PMID- 23114486
TI  - Evaluation and management of mild traumatic brain injury: an Eastern Association
      for the Surgery of Trauma practice management guideline.
AB  - BACKGROUND: An estimated 1.1 million people sustain a mild traumatic brain injury
      (MTBI) annually in the United States. The natural history of MTBI remains poorly
      characterized, and its optimal clinical management is unclear. The Eastern
      Association for the Surgery of Trauma had previously published a set of practice
      management guidelines for MTBI in 2001. The purpose of this review was to update
      these guidelines to reflect the literature published since that time. METHODS:
      The PubMed and Cochrane Library databases were searched for articles related to
      MTBI published between 1998 and 2011. Selected older references were also
      examined. RESULTS: A total of 112 articles were reviewed and used to construct a
      series of recommendations. CONCLUSION: The previous recommendation that brain
      computed tomographic (CT) should be performed on patients that present acutely
      with suspected brain trauma remains unchanged. A number of additional
      recommendations were added. Standardized criteria that may be used to determine
      which patients receive a brain CT in resource-limited environments are described.
      Patients with an MTBI and negative brain CT result may be discharged from the
      emergency department if they have no other injuries or issues requiring
      admission. Patients taking warfarin who present with an MTBI should have their
      international normalized ratio (INR) level determined, and those with
      supratherapeutic INR values should be admitted for observation. Deficits in
      cognition and memory usually resolve within 1 month but may persist for longer
      periods in 20% to 40% of cases. Routine use of magnetic resonance imaging,
      positron emission tomography, nuclear magnetic resonance, or biochemical markers
      for the clinical management of MTBI is not supported at the present time.

PMID- 23114487
TI  - Evaluation and management of penetrating lower extremity arterial trauma: an
      Eastern Association for the Surgery of Trauma practice management guideline.
AB  - BACKGROUND: Extremity arterial injury after penetrating trauma is common in
      military conflict or urban trauma centers. Most peripheral arterial injuries
      occur in the femoral and popliteal vessels of the lower extremity. The Eastern
      Association for the Surgery of Trauma first published practice management
      guidelines for the evaluation and treatment of penetrating lower extremity
      arterial trauma in 2002. Since that time, there have been advancements in the
      management of penetrating lower extremity arterial trauma. As a result, the
      Practice Management Guidelines Committee set out to develop updated guidelines.
      METHODS: A MEDLINE computer search was performed using PubMed (www.pubmed.gov).
      The search retrieved English language articles regarding penetrating lower
      extremity trauma from 1998 to 2011. References of these articles were also used
      to locate articles not identified through the MEDLINE search. Letters to the
      editor, case reports, book chapters, and review articles were excluded. The
      topics investigated were prehospital management, diagnostic evaluation, use of
      imaging technology, the role of temporary intravascular shunts, use of
      tourniquets, and the role of endovascular intervention. RESULTS: Forty-three
      articles were identified. From this group, 20 articles were selected to construct
      the guidelines. CONCLUSION: There have been changes in practice since the
      publication of the previous guidelines in 2002. Expedited triage of patients is
      possible with physical examination and/or the measurement of ankle-brachial
      indices. Computed tomographic angiography has become the diagnostic study of
      choice when imaging is required. Tourniquets and intravascular shunts have
      emerged as adjuncts in the treatment of penetrating lower extremity arterial
      trauma. The role of endovascular intervention warrants further investigation.

PMID- 23114488
TI  - Prophylactic antibiotic use in penetrating abdominal trauma: an Eastern
      Association for the Surgery of Trauma practice management guideline.
AB  - BACKGROUND: The use of prophylactic antibiotics in penetrating abdominal trauma
      has resulted in decreased infection rates. The Eastern Association for the
      Surgery of Trauma (EAST) first published its practice management guidelines
      (PMGs) for the use of prophylactic antibiotics in penetrating abdominal trauma in
      1998. During the next decade, several new prospective studies were published on
      this topic. In addition, the practice of damage control laparotomy became widely
      used, and additional questions arose as to the role of prophylactic antibiotics
      in this setting. Thus, the EAST Practice Management Guidelines Committee set out
      to update the original PMG. METHODS: A search of the National Library of Medicine
      and the National Institutes of Health MEDLINE databases was performed using
      PubMed (www.pubmed.gov) and specific key words. The search retrieved English
      language articles regarding the use of antibiotics in penetrating abdominal
      trauma published from 1973 to 2011. The topics investigated were the need for
      perioperative antibiotics, the duration of antibiotic therapy, the dose of
      antibiotics in patients presenting in hemorrhagic shock, and the appropriate
      duration of antibiotic therapy in the setting of damage control laparotomy.
      RESULTS: Forty-four articles were identified for inclusion in this review.
      CONCLUSION: There is evidence to support a Level I recommendation that
      prophylactic antibiotics should only be administered for 24 hours in the presence
      of a hollow viscus injury. In addition, there are no data to support continuing
      prophylactic antibiotics longer than 24 hours in damage control laparotomy.

PMID- 23114489
TI  - Screening for thoracolumbar spinal injuries in blunt trauma: an Eastern
      Association for the Surgery of Trauma practice management guideline.
AB  - BACKGROUND: Thoracolumbar spine (TLS) injuries have an incidence rate of 5% in
      blunt trauma patients. The Eastern Association for the Surgery of Trauma
      published Practice Management Guidelines for the Screening of Thoracolumbar Spine
      Fracture in 2007. The Practice Management Guidelines Committee was assembled to
      reevaluate the literature. METHODS: A search of the United States National
      Library of Medicine and the National Institutes of Health database was performed
      using MEDLINE through PubMed (www.pubmed.gov). The search retrieved English
      language articles from March 2005 to December 2011 that referenced traumatic TLS
      injuries and fractures. The questions posed were the following: (1) What is the
      appropriate imaging modality to screen patients for TLS injuries? (2) Which
      trauma patients require radiographic screening for TLS injuries? (3)Does a
      patient who is awake and alert without distracting injuries require radiologic
      workup to rule out TLS injuries? RESULTS: Thirty-seven articles that referenced
      traumatic TLS injuries in association with screening published between March 2005
      and December 2011 were collected and disseminated to the committee. Twelve were
      found to be relevant. Nine publications from the previous 2006 guidelines were
      reviewed and referenced to create and validate the updated guidelines.
      CONCLUSION: Practice patterns have changed regarding screening blunt trauma
      patients for TLS injuries. Software reformatted multidetector computed
      tomographic scans are more sensitive and accurate than plain films. Multidetector
      computed tomographic scans have become the screening modality of choice and the
      criterion standard in screening for TLS injuries. The literature supports a Level
      1 recommendation to validate this based on a preponderance of Class II data.
      Patients without altered mentation or significant mechanism may be excluded by
      clinical examination without imaging. Patients with gross neurologic deficits or
      concerning clinical examination findings with negative imaging should receive a
      magnetic resonance imaging expediently, and the spine service should be
      consulted.

PMID- 23114490
TI  - Emergency tracheal intubation immediately following traumatic injury: an Eastern
      Association for the Surgery of Trauma practice management guideline.
AB  - BACKGROUND: The ABCs of trauma resuscitation begin with the airway evaluation,
      and effective airway management is imperative in the care of a patient with
      critical injury. The Eastern Association for the Surgery of Trauma Practice
      Management Guidelines committee aimed to update the guidelines for emergency
      tracheal intubation (ETI) published in 2002. These guidelines were made to assist
      clinicians with decisions regarding airway management for patients immediately
      following traumatic injury. The goals of the work group were to develop evidence
      based guidelines to (1) characterize patients in need of ETI and (2) delineate
      the most appropriate procedure for patients undergoing ETI. METHODS: A search of
      the National Library of Medicine and the National Institutes of Health MEDLINE
      database was performed using PubMed (www.pubmed.gov). RESULTS: The search
      retrieved English-language articles published from 2000 to 2012 involving
      patients who had sustained blunt trauma, penetrating trauma, or heat-related
      injury and had developed respiratory system insufficiency or required ETI in the
      immediate period after injury (first 2 hours after injury). Sixty-nine articles
      were used to construct this set of practice management guidelines. CONCLUSION:
      The data supported the formation of six Level 1 recommendations, four Level 2
      recommendations, and two Level 3 recommendations. In summary, the decision to
      intubate a patient following traumatic injury is based on multiple factors,
      including the need for oxygenation and ventilation, the extent and mechanism of
      injury, predicted operative need, or progression of disease. Rapid sequence
      intubation with direct laryngoscopy continues to be the recommended method for
      ETI, although the use of airway adjuncts such as blind insertion supraglottic
      devices and video laryngoscopy may be useful in facilitating successful ETI and
      may be preferred in certain patient populations. There is no pharmacologic
      induction agent of choice for ETI; however, succinylcholine is the neuromuscular
      blockade agent recommended for rapid sequence intubation.

PMID- 23114491
TI  - Presumptive antibiotic use in tube thoracostomy for traumatic hemopneumothorax:
      an Eastern Association for the Surgery of Trauma practice management guideline.
AB  - BACKGROUND: Antibiotic use in injured patients requiring tube thoracostomy (TT)
      to reduce the incidence of empyema and pneumonia remains a controversial
      practice. In 1998, the Eastern Association for the Surgery of Trauma (EAST)
      developed and published practice management guidelines for the use of presumptive
      antibiotics in TT for patients who sustained a traumatic hemopneumothorax. The
      Practice Management Guidelines Committee of EAST has updated the 1998 guidelines
      to reflect current literature and practice. METHODS: A systematic literature
      review was performed to include prospective and retrospective studies from 1997
      to 2011, excluding those studies published in the previous guideline. Case
      reports, letters to the editor, and review articles were excluded. Ten acute care
      surgeons and one statistician/epidemiologist reviewed the articles under
      consideration, and the EAST primer was used to grade the evidence. RESULTS: Of
      the 98 articles identified, seven were selected as meeting criteria for review.
      Two questions regarding presumptive antibiotic use in TT for traumatic
      hemopneumothorax were addressed: (1) Do presumptive antibiotics reduce the
      incidence of empyema or pneumonia? And if true, (2) What is the optimal duration
      of antibiotic prophylaxis? CONCLUSION: Routine presumptive antibiotic use to
      reduce the incidence of empyema and pneumonia in TT for traumatic
      hemopneumothorax is controversial; however, there is insufficient published
      evidence to support any recommendation either for or against this practice.

PMID- 23114492
TI  - Evaluation and management of geriatric trauma: an Eastern Association for the
      Surgery of Trauma practice management guideline.
AB  - BACKGROUND: Aging patients constitute an increasing proportion of patients
      treated at trauma centers. Previous and existing guidelines addressing care of
      the injured elder have not adequately addressed emerging data regarding optimal
      means for undertaking triage decisions, correcting coagulopathy, and the
      limitations of supraphysiologic resuscitation. METHODS: More than 400 MEDLINE
      citations published between the years 2000 and 2008 were identified and screened.
      A total of 90 references were selected for the evidentiary table followed by
      consensus-based discussions regarding the level of evidence and the strength of
      recommendations that could be derived from the related findings of the individual
      studies. RESULTS: In general, a lower threshold for trauma activation should be
      used for injured patients aged 65 years or older who are evaluated at trauma
      centers. Furthermore, elderly patients with at least one body system with an AIS
      score of 3 or higher or a base deficit of -6 or less should be treated at trauma
      centers, preferably in intensive care units staffed by surgeon-intensivists. In
      addition, all elderly patients who receive daily therapeutic anticoagulation
      should have appropriate assessment of their coagulation profile and cross
      sectional imaging of the brain as soon as possible after admission where
      appropriate. In patients aged 65 years or older with a Glasgow Coma Scale (GCS)
      score less than 8, if substantial improvement in GCS is not realized within 72
      hours of injury, consideration should be given to limiting further aggressive
      therapeutic interventions. CONCLUSION: Effective evidence-based care of aging
      patients necessitates aggressive triage, correction of coagulopathy, and
      limitation of care when clinical evidence points toward an overwhelming
      likelihood of poor long-term prognosis.

PMID- 23114493
TI  - Management of pulmonary contusion and flail chest: an Eastern Association for the
      Surgery of Trauma practice management guideline.
AB  - BACKGROUND: Despite the prevalence and recognized association of pulmonary
      contusion and flail chest (PC-FC) as a combined, complex injury pattern with
      interrelated pathophysiology, the mortality and morbidity of this entity have not
      improved during the last three decades. The purpose of this updated EAST practice
      management guideline was to present evidence-based recommendations for the
      treatment of PC-FC. METHODS: A query was conducted of MEDLINE, Embase, PubMed and
      Cochrane databases for the period from January 1966 through June 30, 2011. All
      evidence was reviewed and graded by two members of the guideline committee.
      Guideline formulation was performed by committee consensus. RESULTS: Of the 215
      articles identified in the search, 129 were deemed appropriate for review,
      grading, and inclusion in the guideline. This practice management guideline has a
      total of six Level 2 and eight Level 3 recommendations. CONCLUSION: Patients with
      PC-FC should not be excessively fluid restricted but should be resuscitated to
      maintain signs of adequate tissue perfusion. Obligatory mechanical ventilation in
      the absence of respiratory failure should be avoided. The use of optimal
      analgesia and aggressive chest physiotherapy should be applied to minimize the
      likelihood of respiratory failure. Epidural catheter is the preferred mode of
      analgesia delivery in severe flail chest injury. Paravertebral analgesia may be
      equivalent to epidural analgesia and may be appropriate in certain situations
      when epidural is contraindicated.A trial of mask continuous positive airway
      pressure should be considered in alert patients with marginal respiratory status.
      Patients requiring mechanical ventilation should be supported in a manner based
      on institutional and physician preference and separated from the ventilator at
      the earliest possible time. Positive end-expiratory pressure or continuous
      positive airway pressure should be provided. High-frequency oscillatory
      ventilation should be considered for patients failing conventional ventilatory
      modes. Independent lung ventilation may also be considered in severe unilateral
      pulmonary contusion when shunt cannot be otherwise corrected.Surgical fixation of
      flail chest may be considered in cases of severe flail chest failing to wean from
      the ventilator or when thoracotomy is required for other reasons. Self-activating
      multidisciplinary protocols for the treatment of chest wall injuries may improve
      outcome and should be considered where feasible.Steroids should not be used in
      the therapy of pulmonary contusion. Diuretics may be used in the setting of
      hydrostatic fluid overload in hemodynamically stable patients or in the setting
      of known concurrent congestive heart failure.

PMID- 23114494
TI  - Evaluation and management of small-bowel obstruction: an Eastern Association for
      the Surgery of Trauma practice management guideline.
AB  - BACKGROUND: Small-bowel obstruction (SBO) represents as many as 16% of surgical
      admissions and more than 300,000 operations annually in the United States. The
      optimal strategies for the diagnosis and management of SBO continue to evolve
      secondary to advances in imaging techniques, critical care, and surgical
      techniques. This updated systematic literature review was developed by the
      Eastern Association for the Surgery of Trauma to provide up-to-date evidence
      based recommendations for SBO. METHODS: A search of the National Library of
      Medicine MEDLINE database was performed using PubMed interface for articles
      published from 2007 to 2011. RESULTS: The search identified 53 new articles that
      were then combined with the 131 studies previously reviewed by the 2007
      guidelines. The updated guidelines were then presented at the 2012 annual EAST
      meeting. CONCLUSION: Level I evidence now exists to recommend the use of computed
      tomographic scan, especially multidetector computed tomography with multiplanar
      reconstructions, in the evaluation of patients with SBO because it can provide
      incremental clinically relevant information over plains films that may lead to
      changes in management. Patients with evidence of generalized peritonitis, other
      evidence of clinical deterioration, such as fever, leukocytosis, tachycardia,
      metabolic acidosis, and continuous pain, or patients with evidence of ischemia on
      imaging should undergo timely exploration. The remainder of patients can safely
      undergo initial nonoperative management for both partial and complete SBO. Water
      soluble contrast studies should be considered in patients who do not clinically
      resolve after 48 to 72 hours for both diagnostic and potential therapeutic
      purposes. Laparoscopic treatment of SBO has been demonstrated to be a viable
      alternative to laparotomy in selected cases.

PMID- 23114495
TI  - Metabonomic analysis of HIV-infected biofluids.
AB  - Monitoring the progression of HIV infection to full-blown acquired immune
      deficiency syndrome (AIDS) and assessing responses to treatment will benefit
      greatly from the identification of novel biological markers especially since
      existing clinical indicators of disease are not infallible. Nuclear magnetic
      resonance spectroscopy (NMR) and mass spectrometry (MS) are powerful
      methodologies used in metabonomic analyses for an approximation of HIV-induced
      changes to the phenotype of an infected individual. Although early in its
      application to HIV/AIDS, (biofluid) metabonomics has already identified metabolic
      pathways influenced by both HIV and/or its treatment. To date, biofluid NMR and
      MS data show that the virus and highly active antiretroviral treatment (HAART)
      mainly influence carbohydrate and lipid metabolism, suggesting that infected
      individuals are susceptible to very specific metabolic complications. A number of
      well-defined biofluid metabonomic studies clearly distinguished HIV negative,
      positive and treatment experienced patient profiles from one another. While many
      of the virus or treatment affected metabolites have been identified, the
      metabonomics measurements were mostly qualitative. The identities of the
      molecules were not always validated neither were the statistical models used to
      distinguish between groups. Assigning particular metabolic changes to specific
      drug regimens using metabonomics also remains to be done. Studies exist where
      identified metabolites have been linked to various disease states suggesting
      great potential for the use of metabonomics in disease prognostics. This review
      therefore examines the field of metabonomics in the context of HIV/AIDS, comments
      on metabolites routinely detected as being affected by the pathogen or treatment,
      explains what existing data suggest and makes recommendations on future research.

PMID- 23114496
TI  - Novel Al-based FLP systems.
AB  - Al/P based frustrated Lewis pairs (FLPs) having coordinatively unsaturated
      aluminium and phosphorus atoms in a single molecule were obtained on a multigram
      scale by hydroalumination of alkynylphosphines. Steric shielding prevented the
      formation of adducts and the quenching of the conflicting Lewis acidic and basic
      functionalities. These FLPs reacted with terminal alkynes by C-H bond cleavage
      with the protons bonded to phosphorus and the alkynido groups coordinated to
      aluminium. Alternatively, a five-membered heterocycle was formed by C=C triple
      bond activation. Similar heterocycles resulted from the reversible coordination
      of carbon dioxide. Particularly interesting is their unique propensity to react
      as effective ion pair receptors for the complexation of alkali metal hydrides and
      their capability to activate such ionic hydrides as phase transfer catalysts.
      Sterically less shielded compounds gave dimers via Al-P interactions. These
      compounds are still active as masked FLPs and form complexes with carbon dioxide
      or phenyl isocyanate. Alternative routes gave methylene bridged Al-P compounds
      which were also shown to coordinate CO2. Bimolecular systems exhibit similar
      properties. They activate terminal alkynes and isobutene or reduce CO2 to
      methanol and carbon monoxide. Hydroalumination of ynamines proved to be an
      excellent method for the generation of Al/N based Lewis pairs. These compounds
      were shown to activate phenylethyne reversibly or to undergo insertion reactions
      with carbodiimide. The constitution of the latter products is determined by
      cooperative interactions between aluminium and nitrogen.

PMID- 23114497
TI  - FLP-mediated activations and reductions of CO2 and CO.
AB  - This chapter reviews the published work to date on the interaction of CO2 and CO
      with frustrated Lewis pairs (FLPs). The ability of FLP-derived systems reversibly
      to bind and release CO2 is a dramatic and exciting development, offering new
      routes to sequester this environmentally important molecule. Furthermore, in
      combination with FLPs' documented ability to cleave H2 heterolytically, new CO2
      hydrogenation chemistry has been uncovered. Novel tandem catalytic processes
      involving FLPs are beginning to be developed which allow the chemical
      functionalisation of CO2. Structure-function relationships which affect the
      thermal stability of FLP-CO2 adducts are highlighted, alongside an insight
      towards the future design of successful FLP-mediated CO2 hydrogenation catalysts.

PMID- 23114498
TI  - Computational design of metal-free molecules for activation of small molecules,
      hydrogenation, and hydroamination.
AB  - Hydrogen activation is a key step in hydrogenation reactions which are widely
      used in both laboratory synthesis and the chemical industry. Traditionally, it
      was often considered that only transition metal complexes/systems are able to
      activate hydrogen and to catalyze hydrogenations. This view has been changed
      recently; more and more metal-free molecules/systems have been found capable of
      activating hydrogen. Among these developments, the frustrated Lewis pairs (FLPs)
      are of particular significance, not only because they exhibit high reactivity
      toward hydrogen as well as other small molecules, but also because some of them
      can perform direct catalytic hydrogenations, which pave the way to the
      development of cheaper and greener hydrogenation catalysts. Inspired by the FLP
      principle, we used quantum mechanics computations to design molecules for H2,
      CH4, and NH3 activation and catalysts for hydrogenation of imines, ketones, and
      alkenes. While our designed molecules are awaiting experimental preparation, the
      active sites in our designed molecules anticipated the features appeared in the
      compounds synthesized later by experimentalists. This chapter reviews our
      computational explorations to enrich FLP chemistry.

PMID- 23114499
TI  - Ageing in a system of polydisperse goethite boardlike particles showing rich
      phase behaviour.
AB  - Using microradian x-ray scattering and polarized light microscopy the rich liquid
      crystalline phase behaviour of a polydisperse system of chromium-modified
      goethite particles has been studied for five years. We observe that the particles
      stay highly mobile over years and the rich phase behaviour keeps developing in
      novel and even surprising ways. While in many other colloidal systems particle
      size polydispersity suppresses the formation of ordered phases, goethite
      particles form multiple coexisting ordered phases. The particle polydispersity
      problem is then solved by particle exchange between coexisting phases. One
      usually expects that a less ordered phase (e.g., nematic) is formed first while
      crystallization of the smectic and columnar crystals might take a longer time.
      For goethite particles we find the opposite, i.e. the nematic phase grows over
      years at the expense of a better ordered smectic phase. Moreover, SAXS patterns
      revealed peak splitting for both the smectic and the columnar phase, meaning that
      the system displays fractionated crystallization. We further discovered that the
      centred rectangular columnar phase spontaneously forms out of the simple
      rectangular columnar phase. The reverse transition is observed as well. We
      explain the ease of these martensitic transitions by showing how slight rotation
      and translation of the particles triggers the transition.

PMID- 23114501
TI  - Rational design of light-directed dynamic spheres.
AB  - We created light-directed dynamic spheres based on simple azobenzene monomers
      showing (i) a high yield of reversible trans<->cis photoisomerization and (ii)
      noticeable phase transition from crystalline to isotropic states under UV light
      irradiation at ambient temperature.

PMID- 23114500
TI  - Common threads in cardiac fibrosis, infarct scar formation, and wound healing.
AB  - Wound healing, cardiac fibrosis, and infarct scar development, while possessing
      distinct features, share a number of key functional similarities, including
      extracellular matrix synthesis and remodeling by fibroblasts and myofibroblasts.
      Understanding the underlying mechanisms that are common to these processes may
      suggest novel therapeutic approaches for pathologic situations such as fibrosis,
      or defective wound healing such as hypertrophic scarring or keloid formation.
      This manuscript will briefly review the major steps of wound healing, and will
      contrast this process with how cardiac infarct scar formation or interstitial
      fibrosis occurs. The feasibility of targeting common pro-fibrotic growth factor
      signaling pathways will be discussed. Finally, the potential exploitation of
      novel regulators of wound healing and fibrosis (ski and scleraxis), will be
      examined.

PMID- 23114502
TI  - Integrated production of lactic acid and biomass on distillery stillage.
AB  - The possibilities of parallel lactic acid and biomass production in batch and fed
      batch fermentation on distillery stillage from bioethanol production were
      studied. The highest lactic acid yield and productivity of 92.3 % and 1.49 g L(
      1) h(-1) were achieved in batch fermentation with initial sugar concentration of
      55 g L(-1). A significant improvement of the process was achieved in fed-batch
      fermentation where the concentration of lactic acid was increased to 47.6 % and
      volumetric productivity for 21 % over the batch process. A high number of
      Lactobacillus rhamnosus ATCC 7469 viable cells of 10(9) CFU ml(-1) was attained
      at the end of fed-batch fermentation. The survival of 92.9 % of L. rhamnosus
      cells after 3 h of incubation at pH 2.5 validated that the fermentation media
      remained after lactic acid removal could be used as a biomass-enriched animal
      feed thus making an additional value to the process. 

PMID- 23114504
TI  - A pilot study of sunitinib malate in patients with metastatic uveal melanoma.
AB  - The prognosis of patients with metastatic uveal melanoma is poor and there are
      limited therapeutic options. C-kit is expressed in the majority of patients with
      metastatic uveal melanoma. In this pilot trial, we examined the toxicity and
      efficacy of sunitinib malate, a multitarget tyrosine kinase inhibitor, in
      patients with metastatic uveal melanoma. Twenty patients with metastatic uveal
      melanoma expressing c-kit, 17 of whom failed previous treatments, were included
      in this study. Patients received sunitinib malate 37.5 mg daily continuously in 4
      week cycles. The evaluation of response was carried out every 8 weeks. The
      overall survival (OS) and progression-free survival (PFS) were evaluated using
      Kaplan-Meier survival curves and differences in survivals were tested using the
      log-rank test. There was one partial response and 12 stable disease (SD) after
      sunitinib treatment. The median OS and PFS were 8.2 and 4.2 months, respectively.
      Three patients had SD for more than 12 months with sunitinib after failing
      previous treatments. The most common adverse events were fatigue (90%), diarrhea
      (60%), hemorrhage (55%), anorexia (45%), hand-foot syndrome (25%), hypothyroidism
      (25%), and rash (25%). Eleven patients required a dose reduction to 25 mg daily
      secondary to grade 3 adverse events. The degree of c-kit expression in melanoma
      cells was not associated with longer PFS or OS. Patients who developed systemic
      metastases after more than 5 years of their initial diagnosis had better PFS
      (median PFS: 5.8 vs. 2.6 months, P=0.005). Sunitinib was safely administered and
      showed potential clinical benefit in patients with metastatic uveal melanoma. The
      lack of a correlation between c-kit expression and clinical outcomes requires
      further investigation on the mechanism of sunitinib in metastatic uveal melanoma.

PMID- 23114506
TI  - [Fungal infections].

PMID- 23114503
TI  - Challenges in estimating the validity of dietary acrylamide measurements.
AB  - BACKGROUND: Acrylamide is a chemical compound present in tobacco smoke and food,
      classified as a probable human carcinogen and a known human neurotoxin.
      Acrylamide is formed in foods, typically carbohydrate-rich and protein-poor plant
      foods, during high-temperature cooking or other thermal processing. The
      objectives of this study were to compare dietary estimates of acrylamide from
      questionnaires (DQ) and 24-h recalls (R) with levels of acrylamide adduct (AA) in
      haemoglobin. METHODS: In the European Prospective Investigation into Cancer and
      Nutrition (EPIC) study, acrylamide exposure was assessed in 510 participants from
      9 European countries, randomly selected and stratified by age, sex, with equal
      numbers of never and current smokers. After adjusting for country, alcohol
      intake, smoking status, number of cigarettes and energy intake, correlation
      coefficients between various acrylamide measurements were computed, both at the
      individual and at the aggregate (centre) level. RESULTS: Individual level
      correlation coefficient between DQ and R measurements (r DQ,R) was 0.17, while r
      DQ,AA and r R,AA were 0.08 and 0.06, respectively. In never smokers, r DQ,R, r
      DQ,AA and r R,AA were 0.19, 0.09 and 0.02, respectively. The correlation
      coefficients between means of DQ, R and AA measurements at the centre level were
      larger (r > 0.4). CONCLUSIONS: These findings suggest that estimates of total
      acrylamide intake based on self-reported diet correlate weakly with biomarker AA
      Hb levels. Possible explanations are the lack of AA levels to capture dietary
      acrylamide due to individual differences in the absorption and metabolism of
      acrylamide, and/or measurement errors in acrylamide from self-reported dietary
      assessments, thus limiting the possibility to validate acrylamide DQ
      measurements.

PMID- 23114507
TI  - [Dermatomycoses due to pets and farm animals : neglected infections?].
AB  - Dermatomycoses due to contact with pets and livestock frequently affect children
      and young adults. Zoophilic dermatophytes are the main important causative
      agents. It has long been known that the often high inflammatory dermatophytoses
      of the skin and the scalp are caused mostly by Microsporum canis. Due to an
      absence of an obligation for reporting fungal infections of the skin to the
      Public Health Office in Germany, an unnoticed but significant change in
      responsible pathogens has occurred. Today an increasing number of infections due
      to zoophilic strains of Trichophyton interdigitale (formerly Trichophyton
      mentagrophytes) and Trichophyton species of Arthroderma benhamiae are found. The
      latter mentioned dermatophyte is the anamorph species of the teleomorph
      Arthroderma benhamiae, which originally was isolated in the Far East (Japan).
      Source of infection of these dermatophytes are small rodents, in particular
      guinea pigs. These animals are bought in pet shops by the parents of those
      children who later are affected by the fungal infection. The coincidental
      purchase of the relevant fungal pathogen is not obvious to the parents. As a
      consequence, highly contagious dermatophytoses occur, often tinea capitis
      sometimes with kerion formation. Further dermatophytes should be considered as
      cause of a zoophilic dermatomycosis. Both Trichophyton verrucosum, the cause of
      the ringworm in cattle, and Trichophyton erinacei following contact to hedgehogs
      are worthy of note. Yeasts cannot be ignored as cause of dermatomycosis,
      especially Malassezia pachydermatis, the only non-lipophilic species within the
      genus Malassezia, which can be transferred from dog to men. Cryptococcus
      neoformans also comes from animal sources. The mucous yeast occurs in bird's
      dropping, and it causes both pulmonary and central nervous system infections, but
      also primary and secondary cutaneous cryptococcosis in immunocompromised patients
      (HIV/AIDS) as possible consequence after contact to these animals.

PMID- 23114508
TI  - [Pityriasis versicolor : new aspects of an old disease].
AB  - Pityriasis versicolor (PV) is one of the most common infectious skin diseases, as
      well as the most common dermatosis associated with pigmentation alterations of
      the skin. PV is prevalent in 1% of the population living in temperate climate
      zones and more common during the summer. In tropical areas, PV is found in up to
      50% of all patients consulting a dermatologist. Of the known Malassezia species,
      M. globosa is currently felt to play a key role in the pathogenesis of PV, as it
      is most commonly found in PV lesions. In addition, its round-shaped cells may
      contribute to the characteristic histology of the disease ("spaghetti and
      meatballs"). However, the clinical appearance of PV including hyper- and
      hypopigmentation, fluorescence of the lesions, as well as a lack of inflammation
      despite high fungal load cannot fully be explained by the presence of M. globosa,
      which is also found on healthy skin. In M. furfur a tryptophan-dependent
      metabolic pathway generates a number of indole pigments, which may be associated
      with the clinical appearance of PV. In the model organism Ustilago maydis it was
      shown that the formation of the indole compounds occurs spontaneously after
      initial conversion of tryptophan into indole pyruvate controlled by the key
      enzyme aminotransferase Tam 1. We review the present knowledge of PV and
      highlight the potential role of Tam1 in explaining the poorly understood aspects
      of the disease. Promising therapeutic results using the application of Tam1
      inhibitors to treat PV support the enzyme's important role in the disease
      pathogenesis.

PMID- 23114509
TI  - [Systemic therapy for malignant melanoma].
AB  - For decades dacarbazine was the standard in the therapy for metastatic melanoma
      even though response rates were low. In recent years multiple pharmacological
      approaches have led to new therapy options including immune modulators like anti
      CTLA4 antibodies and kinase inhibitors of the MAPK signaling pathway that showed
      better response rates and increased overall survival. However, since immune
      modulators lead only in a small subgroup of patients to long-term responses and
      kinase inhibitors lose their function due to development of resistance after
      several months, continuation of clinical studies is strongly required. Classical
      chemotherapeutic drugs will remain a basic part of the therapy especially as
      combinations of different treatment options have to be focused on in order to
      achieve better long-term survival rates.

PMID- 23114510
TI  - [Who examines the oral mucosa during the total body skin examination?].
AB  - Using the example of a 72-year-old male patient, the following questions are
      posed to the reader: Who asks his patients: "Open your mouth please", "Please
      elevate your tongue", or who uses, if possible, his dermatoscope to examine a
      suspicious and reachable lesion of the mucosa? In this patient a bruise-like red
      tumor was found in the sublingual area but had completely disappeared by the
      follow-up after 6 weeks.  To protect the dermatoscope when it is used on the
      mucosa, it can be covered with plastic food wrap.

PMID- 23114511
TI  - Synthesis, structures, and magnetic properties of a family of 3d-4f [Na2Fe6Ln2]
      complexes (Ln = Y, Gd and Dy): effect of ligands on the connection of inorganic
      subunits.
AB  - A family of 3d-4f heterometallic compounds
      [Na(2)Fe(III)(6)Dy(III)(2)(N(3))(4)(HL)(4)(CH(3)O)(4)(PhCO(2))(6)] (1, H(4)L = 2
      {[(2-hydroxy-3-methoxyphenyl)methylene]amino}-2-(hydroxymethyl)-1,3-propanediol),
      [Na(2)Fe(III)(6)Dy(III)(2)(N(3))(4)(L')(4)(CH(3)O)(4)(PhCO(2))(6)(H(2)O)] (2,
      H(3)L' = (E)-2-ethyl-2-(2-hydroxy-3-methoxybenzylideneamino)propane-1,3-diol),
      [Na(2)Fe(III)(6)Dy(III)(2)(N(3))(4)(L')(4)(CH(3)O)(4)(Bu(t)CO(2))(6)] (3)
      [Na(2)Fe(III)(6)Y(III)(2)(N(3))(4)(L')(4)(CH(3)O)(4)(PhCO(2))(6)(H(2)O)] (4), and
      [Na(2)Fe(III)(6)Gd(III)(2)(N(3))(4)(L')(4)(CH(3)O)(4)(PhCO(2))(6)(CH(3)OH)(2)]
      (5) have been prepared using Schiff-base ligands, trinuclear iron precursor
      complexes, azides and lanthanide nitrates as reactants. In compounds 1 and 2, the
      structure of the [Na(2)Fe(III)(6)Dy(III)(2)] cluster forms a couple of cis,trans
      isomers with substitution of methyl for a free hydroxyl group which belongs to
      the Schiff-base ligand. When the pivalates are employed instead of bulkier
      benzoates, the trans-[Na(2)Fe(III)(6)Dy(III)(2)] clusters act as network nodes in
      the formation of rhombic grid-like layered structures in compound 2. Compounds 2,
      4 and 5 have similar metallic cores, only with different crystal solvent
      molecules. The magnetic measurements on all the compounds indicate dominant
      antiferromagnetic interactions between the metal centers.

PMID- 23114512
TI  - Acceptability of potential rectal microbicide delivery systems for HIV
      prevention: a randomized crossover trial.
AB  - We assessed the acceptability of three of over-the-counter products
      representative of potential rectal microbicide (RM) delivery systems. From 2009
      to 2010, 117 HIV-uninfected males (79 %) and females (21 %) who engage in
      receptive anal intercourse participated in a 6-week randomized crossover
      acceptability trial. Participants received each of three products (enema,
      lubricant-filled applicator, suppository) every 2 weeks in a randomized sequence.
      CASI and T-ACASI scales assessed product acceptability via Likert responses.
      Factor analysis was used to identify underlying factors measured by each scale.
      Random effects models were fit to examine age and gender effects on product
      acceptability. Three underlying factors were identified: Satisfaction with
      Product Use, Sexual Pleasure, and Ease of Product Use. For acceptability, the
      applicator ranked highest; however, differences between product acceptability
      scores were greatest among females and younger participants. These findings
      indicate that RM delivery systems impact their acceptability and should be
      considered early in RM development to enhance potential use.

PMID- 23114513
TI  - GAD65, GAD67, and GABAT immunostaining in human brain and apparent GAD65 loss in
      Alzheimer's disease.
AB  - The GABAergic system is the main inhibitory neurotransmitter system in the
      vertebrate brain. Although it is well established that the GABAergic system is
      affected in neuropsychiatric disorders, in Alzheimer's disease (AD) it has been
      considered to be relatively spared. In this study we describe the
      immunohistochemical localization of the main enzymes of the GABAergic system;
      glutamate decarboxylase 65 (GAD65), GAD67, and GABA transferase (GABAT) in human
      brain. In neocortex, hippocampus, basal ganglia, and cerebellum, GAD65 and GAD67
      immunoreactivity were found in neuropil granules, possibly axonal boutons or
      terminals, and in a subset of small to midsized neurons. GAD65 preferentially
      stained neuropil granules, while GAD67 preferentially stained neuronal cell
      bodies. GABAT intensely labeled many types of neurons and glia cells. While GAD65
      and GAD67 stained the cytoplasm of cells homogeneously, GABAT labeling appeared
      irregular and granular. GAD65 immunoreactivity of neurons and neuropil was
      severely reduced in AD middle temporal gyrus, hippocampus, and putamen as
      determined by fluorescence and light microscopic immunohistochemistry. Western
      blotting revealed a similar reduction of GAD65, but not GAD67, protein levels in
      the middle temporal gyrus of AD. Our results suggest that the GABAergic system is
      more severely affected in AD than previously reported. This deficit may
      contribute to AD pathogenesis by loss of GABAergic inhibitory activity.

PMID- 23114514
TI  - Frequency and clinicopathological characteristics of presenilin 1 Gly206Ala
      mutation in Puerto Rican Hispanics with dementia.
AB  - The frequency and clinical and pathological characteristics associated with the
      Gly206Ala presenilin 1 (PSEN1) mutation in Puerto Rican and non-Puerto Rican
      Hispanics were evaluated at the University of Pennsylvania's Alzheimer's Disease
      Center. DNAs from all cohort subjects were genotyped for the Gly206Ala PSEN1
      mutation. Carriers and non-carriers with neurodegenerative disease dementias were
      compared for demographic, clinical, psychometric, and biomarker variables.
      Nineteen (12.6%) of 151 unrelated subjects with dementia were discovered to carry
      the PSEN1 Gly206Ala mutation. Microsatellite marker genotyping determined a
      common ancestral haplotype for all carriers. Carriers were all of Puerto Rican
      heritage with significantly younger age of onset, but otherwise were clinically
      and neuropsychologically comparable to those of non-carriers with AD. Three
      subjects had extensive topographic and biochemical biomarker assessments that
      were also typical of non-carriers with AD. Neuropathological examination in one
      subject revealed severe, widespread plaque and tangle pathology without other
      meaningful disease lesions. The PSEN1 Gly206Ala mutation is notably frequent in
      unrelated Puerto Rican immigrants with dementia in Philadelphia. Considered
      together with the increased prevalence and mortality of AD reported in Puerto
      Rico, these high rates may reflect hereditary risk concentrated in the island
      which warrants further study.

PMID- 23114515
TI  - Low endogenous and chemical induced heat shock protein induction in a 0N3Rtau
      expressing Drosophila larval model of Alzheimer's disease.
AB  - Reduction of tau phosphorylation and aggregation by manipulation of heat shock
      protein (HSP) molecular chaperones has received much attention in attempts to
      further understand and treat tauopathies such as Alzheimer's disease. We examined
      whether endogenous HSPs are induced in Drosophila larvae expressing human tau (3R
      tau) in motor neurons, and screened several chemical compounds that target the
      HSP system using medium-throughput behavioral analysis to assay their effects on
      tau-induced neuronal dysfunction in vivo. Tau-expressing larvae did not show a
      significant endogenous HSP induction response, whereas robust induction of hsp70
      was detectable in a similar larval model of polyglutamine disease. Although pan
      neuronal tau expression augmented the induction of hsp70 following heat shock,
      several candidate HSP inducing compounds induced hsp70 protein in mammalian cells
      in vitro but did not detectably induce hsp70 mRNA or protein in tau expressing
      larvae. The hsp90 inhibitors 17-AAG and radicicol nevertheless caused a dose
      dependent reduction in total human tau levels in transgenic larvae without
      specifically altering tau hyperphosphorylated at S396/S404. These and several
      other HSP modulating compounds also failed to rescue the tau-induced larval
      locomotion deficit in this model. Tau pathology in tau-expressing larvae,
      therefore, induces weak de novo HSP expression relative to other
      neurodegenerative disease models, and unlike these disease models,
      pharmacological manipulation of the hsp90 pathway does not lead to further
      induction of the heat shock response. Forthcoming studies investigating the
      effects of HSP induction on tau-mediated dysfunction/toxicity in such models will
      require more robust, non-pharmacological (perhaps genetic) means of manipulating
      the hsp90 pathway.

PMID- 23114516
TI  - Early measurement of CD34+ cells in peripheral blood after cyclophosphamide and
      granulocyte colony-stimulating factor treatment predicts later CD34+ mobilisation
      failure and is a possible criterion for guiding "on demand" use of plerixafor.
AB  - BACKGROUND: Early identification of predictive factors of failure to mobilise
      CD34+ cells could enable rational use of plerixafor during first mobilisation,
      avoiding the need for a second mobilisation course. However, "on demand"
      administration of plerixafor needs to be driven by established parameters to
      avoid inappropriate use. MATERIALS AND METHODS: To address this issue, we studied
      the value of the peripheral blood CD34+ count, measured early (on days +10, +11,
      +12 and +13), in predicting the mobilisation outcome in the ensuing days. We
      retrospectively collected data from three Italian centres on 233 patients
      affected by multiple myeloma or lymphoma who underwent a first or second attempt
      at mobilisation with cyclophosphamide 4 g/m(2) and granulocyte colony-stimulating
      factor. To assess the diagnostic value of peripheral blood white blood cell and
      CD34+ cell counts with respect to "mobilisation failure", we considered failed
      mobilisation as "disease" and the CD34+ cell count in peripheral blood, on a
      specific day, as a "diagnostic test". For various thresholds, we measured
      sensitivity, false positive rate, specificity and positive predictive value (PPV)
      as well as the area under the receiver-operating characteristic curves (AUC).
      RESULTS: A CD34+ cell count <10 * 10(6)/L on day 13 had high sensitivity (1.00)
      and high specificity (1.00) for predicting subsequent mobilisation failure, with
      an AUC of 1.0. However, good prediction was also obtained using a lower threshold
      (CD34+ cell count: <6 * 10(6)/L) at an earlier time (day 12). The PPV of the day
      13 threshold was 1.00 while that of the day 12 one was 0.87. DISCUSSION: We
      propose that patients with <6 * 10(6)/L CD34+ cells in peripheral blood on day 12
      and <10 * 10(6)/L on day 13 following mobilisation with cyclophosphamide 4 g/m(2)
      and granulocyte colony-stimulating factor are candidates for "on demand" use of
      plerixafor, making the administration of this expensive agent more efficient and
      avoiding its inappropriate use.

PMID- 23114517
TI  - Distribution of Rhesus and Kell blood group frequencies in the Mauritanian
      population.

PMID- 23114518
TI  - An investigation of the spectrum of common and rare inherited coagulation
      disorders in north-eastern Iran.
AB  - BACKGROUND: Health care officials and legislators need accurate data on
      prevalence and numbers of individuals with bleeding disorders in order to plan
      and allot their budgets; the manufacturers of coagulation factors also need these
      data to estimate the amount of factors required to prevent scarcity of these
      products. MATERIALS AND METHODS: We surveyed the prevalence of haemophilia A,
      haemophilia B, von Willebrand's disease and rare bleeding disorders in North
      Eastern Iran. The survey was done in the period from September 2009 to March
      2011. Information was collected from the medical records in three major hospitals
      and a haemophilia centre; the patients' updated data were obtained by telephone.
      RESULTS: Overall in the current survey 552 patients with inherited coagulation
      disorders were identified and their medical records obtained. Of these, 429
      (77.5%) had common bleeding disorders (haemophilia A, haemophilia B, von
      Willebrand's disease), 85 (15.6%) had rare bleeding disorders (deficiency of
      coagulation factors V, VII, X, XIII, I, XI, combined factor V and VIII
      deficiency) and 38 (6.9%) had platelet disorders.The commonest bleeding disorders
      were haemophilia A (n=287, 51.9%), haemophilia B (n=92, 16.6%), von Willebrand's
      disease (n=50, 9%), factor V deficiency (n=21, 3.8%), factor VII deficiency
      (n=19, 3.4%), factor X deficiency (n=2, 0.36%), combined factor V and VIII
      deficiency (n=28, 5.8%), factor XIII deficiency (n=11, 1.99%), factor XI
      deficiency (n=2, 0.4%), afibrinogenaemia (n=2, 0.36%) and platelet disorders
      (n=38, 6.9%). DISCUSSION: There is notable population of individuals with
      bleeding disorders in North-Eastern Iran.

PMID- 23114519
TI  - Ex vivo erythrocyte generation and blood doping.

PMID- 23114520
TI  - Evaluation of the validity of a rapid method for measuring high and low
      haemoglobin levels in whole blood donors.
AB  - BACKGROUND: Haemoglobin screening methods need to be highly sensitive to detect
      both low and high haemoglobin levels and avoid unnecessary rejection of potential
      blood donors. The aim of this study was to evaluate the accuracy of measurements
      by HemoCue in blood donors. MATERIALS AND METHODS: Three hundred and fourteen
      randomly selected, prospective blood donors were studied. Single fingerstick
      blood samples were obtained to determine the donors' haemoglobin levels by
      HemoCue, while venous blood samples were drawn for measurement of the haemoglobin
      level by both HemoCue and an automated haematology analyser as the reference
      method. The sensitivity, specificity, predictive values and correlation between
      the reference method and HemoCue were assessed. Cases with a haemoglobin
      concentration in the range of 12.5-17.9 g/dL were accepted for blood donation.
      RESULTS: Analysis of paired results showed that haemoglobin levels measured by
      HemoCue were higher than those measured by the reference method. There was a
      significant correlation between the reference method and HemoCue for haemoglobin
      levels less than 12.5 g/dL. The correlation was less strong for increasing
      haemoglobin levels. Linear correlation was poor for haemoglobin levels over 18
      g/dL. Thirteen percent of donors, who had haemoglobin levels close to the upper
      limit, were unnecessarily rejected. DISCUSSION: HemoCue is suitable for screening
      for anaemia in blood donors. Most donors at Yazd are males and a significant
      percentage of them have haemoglobin values close to the upper limit for
      acceptance as a blood donor; since these subjects could be unnecessarily rejected
      on the basis of HemoCue results and testing with this method is expensive, it is
      recommended that qualitative methods are used for primary screening and accurate
      quantitative methods used in clinically suspicious cases or when qualitative
      methods fail.

PMID- 23114521
TI  - Successful mobilisation of peripheral blood stem cells in children using
      plerixafor: a case report and review of the literature.

PMID- 23114522
TI  - Product recall: a Croatian experience (2000-2010).
AB  - BACKGROUND: Timely and efficient recall of products known or suspected to be non
      conforming is an important measure in the prevention of adverse events and in
      patients' safety. Product recall in the transfusion service is regulated by
      professional standards and legal acts, but publications presenting results
      related to the implementation of these procedures are quite rare. MATERIALS AND
      METHODS: Data from the Croatian Institute of Transfusion Medicine (CITM) on the
      procedures of product recall during an 11-year period (2000-2010) were
      retrospectively analyzed. Reasons for product recall, their frequency, level of
      severity and efficiency of the procedures are presented and discussed. RESULTS:
      During the study period, there were 245 procedures of product recall, for an
      average of 22 (18-29) procedures/year, all of low extent (1-25 products). Recall
      was required for 1/3,571 blood products issued, while the frequency of laboratory
      test report recalls was 1/5,447 patients. The leading reasons for product recall
      were suspected bacterial contamination of blood products (30.2%) and suspected or
      demonstrated non-conformity of laboratory test reports (28.6%). In total, 99
      (40.4%) product recalls were categorized as class I, 30 (12.2%) as class II and
      116 (47.3%) as class III. DISCUSSION: According to the available literature data,
      the product recall procedures were performed quite infrequently by the CITM and
      were of low extent. There was a remarkable decreasing trend in the rate of
      product recall due to non-conformities or errors made at the CITM, along with a
      constant or increasing rate of recalls because of biological variability of blood
      products.

PMID- 23114523
TI  - Experience in the evaluation of foeto-maternal haemorrhage by flow cytometry.

PMID- 23114524
TI  - Recombinant factor VIIa as haemostatic therapy in advanced liver disease.

PMID- 23114525
TI  - An analysis of the influence of intra-operative blood salvage and autologous
      transfusion on reducing the need for allogeneic transfusion in elective
      infrarenal abdominal aortic aneurysm repair.
AB  - BACKGROUND: An intra-operative cell salvage machine, commonly known as a "cell
      saver", aspirates, washes, and filters patient's blood during an operation so
      that the blood can be returned to the patient's circulation instead of being
      discarded. This procedure could significantly reduce the risks related to the use
      of allogeneic blood and blood products in surgery. The aim of this study was to
      analyse the influence of intra-operative cell salvage on reducing the need for
      allogeneic blood in patients with asymptomatic infrarenal abdominal aortic
      aneurysm undergoing elective repair of the aneurysm. MATERIAL AND METHODS: We
      retrospectively collected data from the clinical records of patients who
      underwent elective infrarenal abdominal aortic aneurysm repair. Two groups were
      formed: the "cell saver" group, in which intra-operative cell salvage was used,
      and the control group, in which a cell saver was not used. RESULTS: Thirty
      patients underwent abdominal aortic aneurysm repair with the use of a cell saver,
      while 32 underwent the same operation without cell salvage. We found a
      significant association between use of the cell saver and a reduced need for
      allogeneic blood in these patients. Operations performed with the use of a cell
      saver lasted, on average, less time than those performed without it. The
      difference between pre-operative and post-operative haemoglobin levels was
      significantly greater in the group of patients who underwent repair with the use
      of a cell saver than in the control group. CONCLUSION: The use of a cell saver in
      elective abdominal aortic aneurysm repair significantly reduces the need for
      intra-operative use of allogeneic blood.

PMID- 23114526
TI  - The second example of anti-Er(b) in a woman during her third pregnancy.

PMID- 23114528
TI  - Blood group A(int) causing uncertainty during organ donor work-up for
      incompatible (A2-O) liver transplantation.

PMID- 23114527
TI  - Real world usage of PCC to "rapidly" correct warfarin induced coagulopathy.
AB  - BACKGROUND: Life threatening bleeding and emergency procedures in patients on
      vitamin K antagonists are indications for urgent reversal with prothrombin
      complex concentrate and vitamin K. Rapid reversal in these situations is
      emphasized in the literature and guidelines, but only very limited information is
      available on its real life use, especially on the timing of treatment in relation
      to presentation. MATERIALS AND METHODS: We retrospectively audited emergency
      warfarin reversal in 131 consecutive patients. We studied the indication, use of
      vitamin K, time between presentation and administration of vitamin K and PCC,
      effectiveness in INR reduction and clinical outcome. RESULTS: The median PCC dose
      was 26.8 IU/kg. The median INR was reduced from 3.1 to 1.2. Vitamin K (5 mg) was
      given in 91.6% of evaluable patients. We found significant delays in
      administration of PCC and vitamin K. The median time between presentation and
      administration of vitamin K/PCC was 3.6 and 5.2 hours respectively. The times in
      intracranial haemorrhage were 2.7 and 3.0 hours and in emergency procedures 17.4
      and 15.9 hours respectively. Mortality related to bleeding was 7.6% overall but
      in patients with intracranial haemorrhage 22.8%. The thrombotic rate within 7
      days of reversal was 1.5%. DISCUSSION: The local protocol for reversal with PCC
      and vitamin K was adhered to well but the delay in pre-procedural patients,
      suggests that intravenous vitamin K alone may be sufficient in many cases and PCC
      administration can be avoided by better planning. Intracranial haemorrhage in
      warfarinised patients carries a high mortality. Treatment delays should be
      avoided by making PCC stocks available within emergency departments, simple
      dosing structures independent of INR and administering PCC without waiting for
      INR and CT scan results in those with strong suspicion of intracranial
      haemorrhage and clear trauma. Future reports and studies should always include
      the time from presentation to PCC treatment.

PMID- 23114529
TI  - ABO blood groups and the risk of venous thrombosis in patients with inherited
      thrombophilia.
AB  - BACKGROUND: Although having a non-O blood type is now regarded as a risk factor
      for venous thromboembolism, the strength of this association is poorly defined,
      as is its interaction with inherited thrombophilia. MATERIALS AND METHODS: The
      prevalence of non-O blood group and inherited thrombophilia (deficiencies of
      natural anticoagulants, factor V Leiden and prothrombin G20210A mutation) was
      assessed in a series of 712 consecutive patients with proximal deep vein
      thrombosis of the lower limbs who were referred to our Institution between 2004
      and 2010, and in 712 age- and gender-matched healthy volunteers. Odds ratios (OR)
      of deep vein thrombosis and their 95% confidence intervals (CI) were computed for
      non-O group and thrombophilia, both separately and in combination. RESULTS: A non
      O blood group was present in 492 cases and 358 controls (OR 2.21; 95% CI, 1.78 to
      2.75). A thrombophilic abnormality was present in 237 cases and 105 controls (OR
      2.82; 2.18 to 3.66). The combination of non-O group and thrombophilia was present
      in 152 cases and 51 controls (OR 7.06; 4.85 to 10.28). DISCUSSION: Having a non-O
      blood group is associated with an increased risk of proximal deep vein thrombosis
      of the lower limbs with or without pulmonary embolism. The addition of inherited
      thrombophilia increases the thrombotic risk conferred by non-O group alone by
      almost 3-fold.

PMID- 23114530
TI  - Non-O blood group: an important genetic risk factor for venous thromboembolism.

PMID- 23114531
TI  - A case of von Hippel-Lindau disease with juxtapapillary retinal capillary
      hemangioma and nutcracker phenomenon.
AB  - The aim of this study was to evaluate a patient with von Hippel-Lindau (VHL)
      syndrome and to discuss the clinical manifestations. A 25-year-old woman
      presented to our clinic with blurred vision for 2 months. Best corrected visual
      acuity in right eye was 20/50, and fundoscopic examination revealed
      juxtapapillary endophytic retinal capillary hemangioma. Examination findings on
      left eye were normal. On optical coherence tomography, exudation was prominent on
      macula. History revealed cerebellar operation because of cerebellar
      hemangioblastoma. On abdominal ultrasonography, liver hemangiomas and pancreatic
      cysts were seen, confirmed by abdominal computerized tomography (CT). Abdominal
      CT imaging also revealed nutcracker phenomenon. Transthoracic echocardiography
      showed atrial septal aneurysm without shunt. The patient refused ocular
      treatment. At 3-month control, ophthalmic findings were the same. To our
      knowledge, this is the first case of VHL disease reported to be associated with
      nutcracker phenomenon and atrial septal aneurysm. Systemic evaluation and regular
      follow-up should be recommended to subjects with VHL disease.

PMID- 23114532
TI  - Induction of tolerance of vascularized composite allografts.
AB  - Vascularized composite allotransplantation has become established as a clinical
      specialty since the first successful hand transplant was performed in 1998. Data
      now available indicate that hand and face transplants offer patients good
      functional outcomes and significant improvements in quality of life. Despite the
      debilitating nature of the injuries treated by such transplants, the defects are
      generally not life threatening, making it difficult for physicians to recommend
      life-long immunosuppression that can itself have grave consequences. One
      potential solution to this dilemma is the induction of immunologic tolerance of
      the tissue transplants because tolerance would eliminate the need for such
      immunosuppression. Transplant tolerance may also prevent chronic rejection, a
      significant source of late graft loss after organ transplantation.Induction of
      mixed hematopoietic chimerism is a robust approach to establishing such
      transplant tolerance, which recently led to the first clinical application of a
      tolerance induction protocol for kidney transplantation. In this manuscript, we
      review the current status of VCA and of research directed toward bringing a
      tolerance approach to the VCA field. We also discuss the potential clinical
      significance of these studies and outline the remaining obstacles to introduction
      of a tolerance induction protocol to clinical practice in hand or face
      transplantation.

PMID- 23114533
TI  - Potential for deceased donation not optimally exploited:  donor action data from
      six countries.
AB  - BACKGROUND: Most countries today promote living donation as an alternative to
      challenge the organ shortage from deceased donors. This seems justifiable
      provided the potential for deceased donation is optimally exploited. METHODS: We
      used the Donor Action (DA) Medical Record Review (MRR) methodology in six
      countries, to measure whether the potential for heart-beating (HB) deceased
      donors was adequately converted to donation. Medical record review data were
      collected from 52,383 patients who died in 605 critical care units in 227
      hospitals between January 2007 and December 2009. RESULTS: On a total of 17,903
      ventilated patients aged younger than 76 years and without contraindications to
      HB donation, 4,855 cases met criteria for brain death (BD) diagnosis and were
      considered potential HB donors. On average, 24.8+/-15.9% was not identified as
      potential donor, 21.9% of identified cases was not referred as such to a
      procurement team, and in 11.3% of identified cases, no approached was offered
      with the option to donate. Average consent rates/family approaches or registry
      consultation was 69.1+/-14.5%, and average conversion of potential into actual
      donors was 42.1+/-7.3%. CONCLUSIONS: Over 57% of deceased potential donors in the
      study cohort were missed along the donation pathway because of nonidentification,
      no referral, no approach of relatives, or objections to donate. In countries with
      lower donation rates, expectedly more potential donors are missed proportionally.
      Efforts to increase the organ pool should therefore focus on optimizing clinical
      practices in deceased organ donation in addition to promoting living organ
      donation.

PMID- 23114534
TI  - The effects of salinity and salinity+metal (chromium and lead) exposure on ATPase
      activity in the gill and intestine of tilapia Oreochromis niloticus.
AB  - Freshwater organisms are highly sensitive to increases in salinity because they
      causes serious osmoregulation problems. Salinity of inland waters can be
      increased as a result of anthropogenic activities. In this study, freshwater fish
      Oreochromis niloticus were exposed individually to increased salinities (0, 2,
      and 8 ppt) alone and salinity+metal [1 MUg/mL chromium (Cr) or lead (Pb) exposure
      at 2 and 8 ppt] exposures for different time periods (1, 7, and 14 days) to
      investigate the response of Na(+)/K(+)-ATPase and Mg(2+)-ATPase in the
      osmoregulatory tissues (gill and intestine). Results showed that enzyme activity
      varied depending on salinity, tissue, metal, and exposure duration. Metal levels
      in controls and salinity-exposed groups were lower than the detection limit,
      although significant Cr and Pb accumulation occurred in the salinity+metal
      combination groups. In salinity-exposed groups, there were increasing trends in
      the enzyme activity, whereas there were decreasing trends in the metal+salinity
      groups. Gill ATPases were more affected by the exposure conditions compared with
      intestine ATPases. Results showed that salinity+metal exposure both played
      significant roles on ATPase activities in the osmoregulatory tissues, although
      the alterations in the activity were mostly insignificant supporting compensation
      mechanisms. Results also suggest that the osmoregulation of freshwater fish
      should be investigated in toxicity- monitoring programs in inland waters.

PMID- 23114535
TI  - DNA copy number alterations and PPARG amplification in a patient with multifocal
      bladder urothelial carcinoma.
AB  - BACKGROUND: Bladder cancer is the seventh most common cancer worldwide and over
      90% are transitional cell carcinoma (TCC). At the first time of diagnosis at
      least 70% of TCC present as superficial bladder cancer. Because the clinical
      outcome of superficial bladder tumors is relatively unpredictable, there is a
      pressing need to identify markers that may predict tumor recurrence and
      progression and new treatment strategies. CASE PRESENTATION: We present a unique
      case of a 67-year old male who underwent total cystectomy after repeated trans
      urethral resections of the bladder for multifocal non-muscle invasive bladder
      cancer. The first and the third tumor were diagnosed as high grade non
      infiltrating (HGNI), while the second as carcinoma in situ (CIS). We performed
      both array comparative genomic hybridization and a targeted chromosomal profile
      by UroVysion in order to detect copy number variations (CNVs) that may be
      involved with tumor recurrence and progression. The overall data from this study
      provide new evidence for the monoclonal origin of urothelial tumor multifocality
      as several genetic changes were found in different tumors of the same patient.
      From the analysis of shared CNVs two gained regions emerged at 3p25.2 and
      12q23.2, including PPARG and ASCL1 genes, respectively. The copy number level of
      these genes would seem inversely mutually correlated and highly dependent on
      histological grade, because the highest level of amplification at 3p25.2 was
      evidenced in the two HGNI samples, while the highest level of copy number gain at
      12q23.2 was reported in the CIS. CONCLUSION: We provide new evidence on the role
      of PPARG in initiation and maintenance of bladder cancer. For the first time we
      also suggest a possible explanation for the elevated expression of PPARG in this
      type of tumor through a focal high level amplification at 3p25.2. Furthermore, a
      new gene, ASCL1, emerged as a potential candidate to assist PPARG in bladder
      carcinogenesis.

PMID- 23114536
TI  - Temperature as an external field for colloid-polymer mixtures: 'quenching' by
      heating and 'melting' by cooling.
AB  - We investigate the response to temperature of a well-known colloid-polymer
      mixture. At room temperature the gas-liquid critical value of the second virial
      coefficient of the effective pairwise colloid-colloid interaction for the Asakura
      Oosawa model predicts the onset of gelation observed experimentally with
      remarkable accuracy. Upon cooling the system the effective attraction between
      colloids induced by polymer depletion is reduced, because the polymer radius of
      gyration decreases as the theta-temperature is approached. Paradoxically this
      raises the effective temperature, leading to 'melting' of colloidal gels. We find
      that the Asakura-Oosawa model of effective colloid interactions, together with a
      simple description of the polymer temperature response, provides a quantitative
      description of the observed location of the fluid-gel transition in the colloid
      volume fraction polymer reservoir number density plane. Further, we present
      evidence for enhancement of crystallization rates in the vicinity of the
      metastable critical point.

PMID- 23114539
TI  - [Oncological nonsurgical treatment concepts for head and neck tumors: highlights
      from the 2012 ASCO annual meeting].

PMID- 23114538
TI  - Influence of HbA1c levels on platelet function profiles associated with tight
      glycemic control in patients presenting with hyperglycemia and an acute coronary
      syndrome. A subanalysis of the CHIPS Study ("Control de HIperglucemia y Actividad
      Plaquetaria en Pacientes con Sindrome Coronario Agudo").
AB  - Patients with hyperglycemia, an acute coronary syndrome and poor glycemic control
      have increased platelet reactivity and poor prognosis. However, it is unclear the
      influence of a tight glycemic control on platelet reactivity in these patients.
      This is a subanalysis of the CHIPS study. This trial randomized patients with
      hyperglycemia to undergo an intensive glucose control (target blood glucose 80
      120 mg/dL), or conventional glucose control (target blood glucose <180 mg/dL). We
      analyzed platelet function at discharge on the subgroup of patients with poor
      glycemic control, defined with admission levels of HbA1c higher than 6.5%. The
      primary endpoint was maximal platelet aggregation following stimuli with 20 MUM
      ADP. We also measured aggregation following collagen, epinephrine, and thrombin
      receptor-activated peptide, as well as P2Y12 reactivity index and surface
      expression of glycoprotein IIb/IIIa and P-selectin. A total of 67 patients
      presented HbA1c >= 6.5% (37 intensive, 30 conventional), while 42 had HbA1c <
      6.5% (20 intensive, 22 conventional). There were no differences in baseline
      characteristics between groups. At discharge, patients with HbA1c >=6.5% had
      significantly reduced MPA with intensive glucose control compared with
      conventional control (46.1 +/- 22.3 vs. 60.4 +/- 20.0%; p = 0.004). Similar
      findings were shown with other measures of platelet function. However, glucose
      control strategy did not affect platelet function parameters in patients with
      HbA1c < 6.5%. Intensive glucose control in patients presenting with an acute
      coronary syndrome and hyperglycemia results in a reduction of platelet reactivity
      only in the presence of elevated HbA1c levels.

PMID- 23114537
TI  - TAVI 2012: state of the art.
AB  - The development of "transcatheter aortic valve implantation (TAVI)" is changing
      the field of cardiovascular medicine rapidly. The basic principle of TAVI is the
      percutaneous implantation of a bioprosthesis mounted in a metal frame. The
      prosthesis, which is attached to the tip of the catheter, is positioned in the
      native aortic valve and expanded. The first successful implantation was made by
      Alain Cribier in 2002. Several smaller mono- and multicenter studies later
      confirmed the technical feasibility of this procedure. Its true value as an
      important, therapeutic alternative to open heart surgery in inoperable and high
      risk patients is now confirmed in large multicenter registries and by the
      prospective, randomized PARTNER trial. Decisive for the future acceptance of the
      procedure and for a possible expansion of the indication spectrum will be (1)
      continuous further development of the implantation technique and the prosthesis
      design, (2) reduction of TAVI-associated complications, (3) confirmation of the
      initial positive long-term results and (4) confirmation of the promising results
      in the treatment of surgical prosthesis dysfunctions and of patients with low to
      intermediate risk.

PMID- 23114540
TI  - [New aspects of current therapeutic strategies in oropharyngeal carcinoma:
      highlights of the 2012 ASCO meeting].
AB  - Beside the surgical treatment of head and neck cancer, the concept of organ and
      function preserving therapy of locally advanced HNSCC (head and neck squamous
      cell carcinoma) especially of oropharyngeal origin is becoming increasingly
      important. The comparison of induction chemotherapy plus chemoradiation and
      primary concomitant chemoradiation has recently been the subject of randomized
      clinical trials. New combinations of different (chemo)radiation regimens and
      targeted therapies are also under investigation for HNSCC. Molecular markers
      predicting treatment efficacy as well as new potential targets are also being
      evaluated in several clinical trials. The good prognosis of HPV-associated HNSCC
      has sparked efforts to deintensify treatment to minimize therapy-related
      toxicities. The impact of specific therapies is growing due to the increasing
      incidence of young patients with HPV-positive carcinomas.

PMID- 23114541
TI  - [New aspects in the therapy of recurrence and metastasis of head and neck cancer:
      highlights from the 2012 ASCO meeting].
AB  - The majority of patients with a squamous cell carcinoma of the head and neck
      region (HNSCC) initially present in a locally advanced stage of the disease.
      Despite aggressive protocols in first-line treatment, some of these patients
      develop locoregional recurrences or metastases and are, in particular,
      extraordinarily challenging for the multidisciplinary treatment team. Therefore,
      among resectability and prior therapy, age, performance status and individual
      expectations of the patient have to be taken into account. Apart from surgical
      options like salvage surgery, chemotherapy and target therapy as well as
      reirradiation are possible treatment concepts. Unfortunately, most treatment
      options offer only little to no survival benefit.

PMID- 23114542
TI  - [The most important results on primary chemoradiation for head and neck squamous
      cell carcinoma: highlights from the 2012 ASCO meeting].
AB  - Primary concomitant and sequential chemoradiation is a commonly used therapeutic
      strategy for head and neck squamous cell carcinoma. At the annual meeting of the
      2012 American Society of Clinical Oncology numerous trial results were presented.
      A selection of the most important trials will be summarized in this article. This
      year, several important results from phase III trials-including the long awaited
      comparison of sequential and concomitant chemoradiation-were demonstrated.

PMID- 23114543
TI  - [Public awareness of human papilloma virus infection in the head and neck area:
      an appeal for precision in diagnostics and for public health awareness].
AB  - Infection with human papilloma virus (HPV) has been associated with head and neck
      carcinomas. Experts in HPV-positive carcinomas consider these carcinomas to be a
      new entity, because it has been shown that treatment outcome is excellent with
      significantly longer overall survival dependent of therapy. Despite this, in
      Germany public awareness of this development is rather low. A strategy for
      prophylactic vaccination against HPV-associated diseases has been available since
      2007 but only to reduce the incidence of cervical cancer for girls between 12 and
      17 years of age. There is an ongoing debate in Germany about the efficacy and
      safety of HPV vaccination. The results of epidemiological research in the USA
      which show that vaccination in young males is valuable are still not accepted in
      Germany. This article discusses the scientific and public awareness regarding
      this topic and calls for precision in diagnostics and public health awareness in
      order to establish a fertile ground for prevention and optimal treatment of HPV
      associated diseases.

PMID- 23114544
TI  - [Painful and rapidly growing exophytic lesion of the vestibular upper lip].
AB  - A 49-year-old healthy woman presented with a painful exophytic-growing mucous
      lesion on her upper lip that had been primarily noted for 2 weeks. The biopsy
      showed histological changes of a dense infiltration of lymphoid cell elements.
      The immunohistological examination presented the diagnosis of primary cutaneous
      CD30-positive large cell T-cell lymphoma. In the diagnosis of oral lesions
      cutaneous CD30-positive large cell T-cell lymphoma constitutes a rare but
      important differential diagnosis.

PMID- 23114546
TI  - Solution mediated phase transformation (RHO to SOD) in porous Co-imidazolate
      based zeolitic frameworks with high water stability.
AB  - Here we report a highly porous, water stable Co based ZIF [CoNIm (RHO)] and its
      solution mediated phase transformation to a less porous and water unstable ZIF
      [CoNIm (SOD)]. CoNIm (RHO) has high Langmuir surface area [2087 m(2) g(-1)] as
      well as high water adsorption [200 cm(3) (STP) g(-1)] capacity.

PMID- 23114545
TI  - [Management of anaphylaxis. Part 1: Causes and pathophysiology].
AB  - Anaphylactic reactions reveal the maximal grade of allergic reactions and are
      potentially life-threatening. The most common agents involved in anaphylactic
      reactions are drugs, food, Hymenoptera, aeroallergens, Latex, and physical
      stress. Anaphylactic reactions are induced by the liberation of various
      mediators. Symptoms are determined by the kind, quantity, and relation of these
      mediators and by the individual predisposition of the patient. In general,
      symptoms occur at the skin, the lungs, the cardiovascular system and the
      gastrointestinal tract. Early treatment of circulatory and pulmonary disturbances
      is decisive for the prognosis of the patient. Adequate therapy has to be given
      immediately according to the severity of symptoms in a step-wise approach. In the
      specific drug-therapy, a few substances have proved to be reliable, e.g.
      adrenalin, histamine antagonists, glucocorticosteroids, oxygen and volume
      substitutes. This article provides an overview of prevalence, symptoms and
      therapeutic options for managing anaphylaxis.

PMID- 23114547
TI  - An overview on standard statistical methods for assessing exposure-outcome link
      in survival analysis (Part II): the Kaplan-Meier analysis and the Cox regression
      method.
AB  - The Kaplan-Meier and the Cox regression methods are the most used statistical
      techniques for performing "time to event analysis" in epidemiological and
      clinical research. The Kaplan-Meier analysis allows to build up one or more
      survival curves describing the occurrence of the outcome of interest over time
      according to the presence/absence of one or more exposures. The Cox regression
      method models the relationship between a specific exposure (either a continuous
      one like age, and systolic blood pressure or a categorical one like diabetes,
      degree of obesity, etc.) and the occurrence of a given outcome taking into
      account multiple confounders and/or predictors.

PMID- 23114548
TI  - Different levels of hypoxia regulate telomere length and telomerase activity.
AB  - This study was designed to identify changes in telomere length and telomerase
      activity in human umbilical vein endothelial cells (HUVECs) exposed to various
      levels of hypoxia. Mild hypoxia (10%, 15% oxygen) increased telomere length,
      which did not appear to change under severe hypoxia (1% oxygen). Telomerase
      activity in HUVECs correlated inversely with oxygen concentration. Endothelial
      cell telomere elongation with telomerase activation in conditions of mild hypoxia
      was demonstrated in this study. High telomerase activity may contribute to
      hypoxia-related telomere elongation. The best cell growth and longest telomere
      length were observed at 10% O(2), and this percentage may therefore be the
      optimal level for maintaining vascular endothelial cells. In addition, elevated
      telomerase activity maintains telomere length within normal range in conditions
      of severe hypoxia (1% O(2)). The telomere length distribution in HUVECs under
      hypoxia seems to be regulated by a balance between telomere attrition by hypoxia
      and telomere elongation by enhanced telomerase activity acting on telomeres,
      perhaps in a telomere-length dependent manner.

PMID- 23114549
TI  - Increased 1-year mortality rates among elderly hip fracture patients with atrial
      fibrillation.
AB  - BACKGROUND AND AIMS: Prediction of factors associated with survival following hip
      fracture is important. We studied crude and adjusted survival rates in elderly
      hip fracture patients with and without atrial fibrillation (AF) to assess
      possible risk of death associated with AF. METHODS: A historical prospective
      cohort study, comprising 1114 consecutive patients with hip fractures. Subjects
      were divided into three groups: patients with sinus rhythm (SR), paroxysmal
      atrial fibrillation (PAF) or chronic atrial fibrillation (CAF). The main outcome
      measures were crude and adjusted survival rates at 30, 90 and 365 days, and end
      of follow-up. RESULTS: AF patients differed from SR patients by gender
      (p=0.0018), age (p=0.008), heart failure (p<0.001), ischemic heart disease
      (p<0.001) and history of a stroke (p<0.001). The lowest death rates were observed
      among SR and PAF patients, whereas CAF patients had the highest rates at each
      follow-up time point. CAF (but not PAF or SR) patients were at a significantly
      higher risk of death at both 365 days and at the end of the study (HR 1.786, CI
      1.011- 3.155 and HR 1.835, CI 1.302-2.585, respectively). Older age (HR 1.301, CI
      1.135-1.491 and HR 1.321, CI 1.321-1.415) and male gender (HR 1.879, CI 1.271-
      2.779 and HR 1.545, CI 1.251-1.909) also predicted higher risk of death at both
      365 days and at the end of the study. CONCLUSIONS: Atrial fibrillation cannot be
      considered to adversely affect short-term survival of hip fracture patients.
      After 365 day, CAF was associated with a significantly higher risk of death.

PMID- 23114550
TI  - Age-associated changes in hand grip and quadriceps muscle strength ratios in
      healthy adults.
AB  - BACKGROUND AND AIMS: Muscle strength may decline with age differentially in the
      upper and lower limbs. This information is difficult to capture through a single
      measure. The present study therefore aimed to characterize the relative changes
      in handgrip and lower limb muscle strength with aging by expressing them as a
      ratio. METHODS: Thirty-eight healthy volunteers aged 20-82 years performed
      maximal voluntary contractions (MVC) of quadriceps and handgrip using a custom
      built transducer and a Jamar dynamometer respectively. RESULTS: The grip
      quadriceps ratios for young adults was similar in males and females (0.75);
      indicating knee extensor force exceeded grip force by approximately 25%. Ratios
      were increased in older adults (p=0.05), and strength of the two muscle groups
      was approximately equal (1.1). Pearson's correlation coefficients for grip
      against quadriceps strength were r=0.63 (young males), r=0.83 (young females),
      r=0.35 (older males) and r=0.05 (older females). CONCLUSIONS: The ratio used
      demonstrated clear differences between the age groups. The reduced muscle
      strength with increasing age was expected, but the higher grip/quadriceps
      strength ratios quantify a greater loss of quadriceps than grip strength with
      aging. It remains to be investigated whether the relatively greater rate of
      decline in quadriceps strength seen in healthy older people is more exaggerated
      in those who are frail, which would have implications for using grip strength as
      a physical marker of lower limb strength and function in those at risk of
      immobility and falls.

PMID- 23114551
TI  - Do behavioral disturbances predict falls among nursing home residents?
AB  - BACKGROUND AND AIMS: The purpose of our study was to examine whether severity of
      dementia, behavioral and psychological symptoms and depression can predict falls
      among nursing home residents, such as demographic variables, activities of daily
      living, and use of psychotropic drugs, when potential confounders are controlled
      for. METHODS: 1147 nursing home residents were examined in this one-year follow
      up study. All residents were examined with the Physical Self-Maintenance scale
      (Activities of Daily Living - ADL), Clinical Dementia Rating Scale (CDR),
      Neuropsychiatric Inventory (NPI) and Cornell Scale for Depression in Dementia.
      Demographic data, gender, education, physical health and use of medication were
      collected from medical records. RESULTS: 40% of participants had at least one
      fall during the one-year follow-up period. Bivariate survival analysis revealed
      that low level of education, severe dementia, severe behavioral and psychological
      symptoms, severe depression, greater functional impairment, age, worsening in
      physical health, and use of sedatives, significantly predict one or more falls.
      Multivariate Cox regression analyses showed that age, higher scores on NPI and
      CDR, use of sedatives and dependency in ADL were all, independently of each
      other, predictors of an increased risk of falling. CONCLUSIONS: Having a high NPI
      score was identified as a significant and independent predictor of falls. Since
      falling is a common event which causes considerable morbidity and mortality in
      older people, these findings are important for healthcare and for the individuals
      concerned. To prevent falling in nursing homes, special attention must be paid to
      residents with severe dementia, to behavioral symptoms and use of sedatives.

PMID- 23114552
TI  - Physical performance and 10-year mortality in a 70-year-old community-dwelling
      population.
AB  - BACKGROUND AND AIMS: Poor physical performance is known to be inversely related
      to mortality. The purpose of the present study was to determine whether an
      association between physical performance and 10-year mortality could be extended
      to a Japanese 70-year-old community-dwelling population, and to compare findings
      with those found in an octogenarian population. METHODS: Seventy-year-old
      subjects residing in Niigata city, Japan, participated. Baseline examinations,
      including a physical performance test of four tests of muscle strength, one test
      of balance, and one test of agility, were carried out in June 1998 for 600
      participants, and these individuals were then followed for 10 years. RESULTS:
      During the 10-year follow up, 80 subjects died. Cox regression analysis with
      adjustment for confounding factors showed that high scores in muscle strength
      tests for lower extremities, such as single-leg and double-leg extensor strength
      and isokinetic leg extensor power, were found to be related to decreases in total
      cause mortality. CONCLUSIONS: In an elderly 70-year-old Japanese community
      dwelling population, poor muscle strength was found to be an independent
      predictor of total mortality. Together with our previous findings in an 80-year
      old population, the association between poor strength and high mortality may have
      effects at 70 but not 80 years of age.

PMID- 23114553
TI  - Atrial electromechanical coupling interval and P-wave dispersion in healthy
      elderly.
AB  - BACKGROUND AND AIMS: The aim of our study was to investigate the potential effect
      of natural aging on atrial fibrillation (AF) by means of electrocardiographic P
      wave analysis and measurement of the transthoracic echocardiographic
      electromechanical coupling interval (EMC). METHODS: The study comprised 25
      healthy individuals aged >=65 years (group 1) and 25 control subjects <65 years
      (group 2). The difference between maximum (Pmax) and minimum (Pmin) P-wave
      durations on 12-lead electrocardiography were defined as P-wave dispersion (PD).
      Intra- and inter-atrial EMC were measured by tissue Doppler imaging. RESULTS:
      Pmax (107.2 +/- 3.58 msec vs 100.0 +/- 3.56 msec, p<0.001) and PD (43.6 +/- 4.98
      msec vs 36.5 +/- 3.56 msec, p<0.001) were significantly higher in group 1 than in
      group 2. Left atrial EMC [24.6 (15.20) vs 13.3 (4.50), p<0.001] and inter-atrial
      EMC [43.2 (16.05) vs 33.3 (4.75), p<0.001] were significantly delayed in group 1
      compared with group 2. There was a significant correlation between left atrial
      diameter, PD, Pmax, left atrial EMC, and inter-atrial EMC. CONCLUSION: Aging is
      correlated with increased left atrial size and impaired diastolic relaxation,
      which may contribute to a greater risk of AF in terms of prolonged PD and atrial
      EMC.

PMID- 23114554
TI  - How should we investigate CUO (C-Reactive Protein elevation of unknown origin)? A
      case-based discussion of infective endocarditis in an octogenarian.
AB  - Infective endocarditis and other chronic infections may cause diagnostic
      difficulties, regardless of age. The likelihood of an atypical presentation of
      chronic infection probably increases with age. Serum CRP may be a useful guide to
      the presence of underlying infection and its resolution in older people. The term
      CUO (CRP elevation of unknown origin) may have a place in triggering further
      investigation for the presence of infection or other pathology.

PMID- 23114555
TI  - Mycophenolate mofetil as steroid-sparing treatment for elderly patients with
      giant cell arteritis: report of three cases.
AB  - BACKGROUND AND AIMS: Glucocorticoids have never been studied in a placebo
      controlled manner in giant cell arteritis (GCA), but their effectiveness is well
      established. However, evidence for the efficacy of immunosuppressant drugs as
      steroid-sparing agents in this disease is highly desirable, especially in elderly
      patients. We report the use of mycophenolate mofetil (MMF) as a steroid-sparing
      agent in three patients (mean age 78 years) with GCA, at high risk of longterm
      high dose glucocorticoids because of type II diabetes mellitus, obesity,
      hypertension or osteoporosis. METHODS: clinical monitoring and assessment of
      laboratory parameters were carried out weekly (first month) and then patients
      were seen in the clinic every 2 weeks. Vascular lesions were also monitored at
      the onset and during the follow-up by Doppler ultrasonography (every 3 months).
      RESULTS: all three patients showed clinical benefit, and were also able to taper
      steroid use to a more rapid regimen compared with the recently suggested steroid
      reduction approach. MMF was well tolerated, and no signs of toxicity were
      observed in a mean of 21.6 months (12-29) of follow-up. CONCLUSION: mycophenolate
      mofetil may be considered a steroid-sparing agent in elderly patients with GCA
      but, before results of controlled trials become available, MMF may be considered
      only for patients who do not improve or stabilize with conventional therapy, or
      in patients for whom reduced steroid dosage is highly recommended.

PMID- 23114556
TI  - Rapid improvement of depressive symptoms and cognition in an elderly patient with
      a single session of piano playing: a clinical treatment report.
AB  - BACKGROUND AND AIMS: Music has been used as a non-pharmacological modality in the
      treatment of different conditions since ancient times. It has received attention
      in modern medicine in recent decades, particularly in geriatric population. The
      effects of music on mood and cognition are well documented. The aim of the
      current case report is to highlight the benefits of musical activities in the
      geriatric population. METHODS: We report a naturalistic treatment outcome in an
      elderly patient on a geriatric psychiatric unit related to a single session of
      piano playing. RESULTS: A rapid and sustained improvement in mood and cognition
      of an elderly patient was observed after a single session of playing piano.
      Notwithstanding the limitations of a single subject, uncontrolled case study, the
      effect was dramatic. CONCLUSION: Our findings support previous claims regarding
      music therapy including effects of a single session music-based therapeutic
      interventions, and we conclude that music therapy for geriatric patients with
      mood and cognitive deficits is worth further systematic investigation.

PMID- 23114557
TI  - A sudden decline in mobility status as an early sign of acute infection in
      elderly patients: evidence from three case reports.
AB  - Early diagnosis of infections is often a challenge in older patients, since this
      age group may have atypical presentation. We report here the cases of 3 old
      patients, in whom a sudden decline in mobility status occurred shortly before the
      onset of the classically recognized features of infection. The decline was
      interpreted as an anticipatory marker of imminent infection. We discuss the
      possible implications of our findings and the opportunity that they offer to
      improve routine clinical practice in older patients.

PMID- 23114558
TI  - Slower adaptation to driving simulator and simulator sickness in older adults.
AB  - BACKGROUND AND AIMS: Methods of assessing driving abilities in the elderly are
      urgently needed. Although the driving simulator (DS) appears to be a safe and
      cost-effective method of objectively evaluating driving performance, it may pose
      adaptation problems for elderly adults. In this study, we examined age-related
      adaptation deficits on the DS. METHODS: Healthy young adults (n=15) and healthy
      elderly persons (n=17) completed some neuropsychological tests, and then
      performed a road-tracking task with the DS, which was repeated four times (Trials
      1-4). RESULTS: After simulated driving in DS, simulator sickness (SS) was
      observed in 18.8% of participants. The frequency of SS was 29.4% in elderly
      adults and 6.7% in young adults, and 17.6% of the elderly participants dropped
      out of the experiment. Performance on the Necker cube copying task was
      significantly correlated with the onset of SS. Driving performance also showed a
      significant interaction between group and trial, for both driving accuracy and
      vehicle speed. In addition, the performance of elderly adults significantly
      improved between trials 1 and 4, reaching a plateau in trial 4, whereas that of
      young adults did not change across trials. CONCLUSION: This study provides
      preliminary evidence of slower adaptation to a DS-based driving task by older
      adults, which was associated with cognitive aging. Age affected driving accuracy
      and velocity when a road-tracking task was simply repeated. It is concluded that
      the capacity of elderly people to adapt to DS environments should be taken into
      consideration when evaluating their performance on DS tasks.

PMID- 23114559
TI  - Effects of intensive strength-power training on sense of coherence among 60-85
      year-old people with hip fracture: a randomized controlled trial.
AB  - BACKGROUND AND AIMS: Older people with disabilities are at increased risk of
      psychological health decline. There are no earlier studies on the effects of
      resistance training on sense of coherence (SOC) among older people with a history
      of hip fracture. The aim of this study is to test the effects of intensive 12
      week strength-power training on SOC among older adults after hip fracture.
      METHODS: A clinical sample of 60-85-year-old community-dwelling men and women was
      studied, 0.5. to 7.0 years after hip fracture. Forty-six had no contraindications
      for participation and were randomized into training (n=24) and control groups
      (n=22). The training group participated in a 12-week, individually tailored,
      strength-power training program, twice a week in a senior gym and supervised by
      an experienced physiotherapist. SOC was assessed with Antonovsky's short 13-item
      scale. Data were collected at baseline and after intervention. RESULTS: Intensive
      12-week strength-power training had no effect on participants' SOC level.
      CONCLUSIONS: Results indicated no change in SOC after 12-week physical exercise
      training among participants after hip fracture. Further studies on SOC among
      older people with disabilities and potential ways of increasing it are needed.

PMID- 23114560
TI  - Asthma phenotypes and endotypes.
AB  - PURPOSE OF REVIEW: It is increasingly clear that asthma is not a single disease,
      but a disorder with vast heterogeneity in pathogenesis, severity, and treatment
      response. In this review, we discuss the present understanding of different
      asthma phenotypes and endotypes, and the prospects of personalized medicine for
      asthma. RECENT FINDINGS: The recognition of diverse biological backgrounds in
      which asthma, and particularly severe asthma, can manifest has prompted the
      search for refined phenotypes and endotypes in asthma. Such appreciation of the
      heterogeneity in asthma is also prompting clinical trials to focus on specific
      subgroups of asthma, as demonstrated by the clinical trial of lebrikizumab.
      SUMMARY: Patients with severe asthma have asthma symptoms that are difficult to
      control, require high dosages of medication, and continue to experience
      persistent symptoms, asthma exacerbations or airflow obstruction even with
      aggressive therapy. Although asthma is traditionally viewed as an eosinophilic
      inflammatory disorder associated with a T-helper cell type 2 (Th2) immune
      response, recent studies have identified involvement of other effector cells,
      nonclassical Th2 cytokines and non-Th2 cytokines in severe asthma pathogenesis.
      Results of several clinical trials of anticytokine antibodies demonstrated the
      effectiveness of tailoring asthma treatment on the basis of an individual's
      biology.

PMID- 23114561
TI  - Comorbidities of asthma:  current knowledge and future research needs.
AB  - PURPOSE OF REVIEW: Asthma is often associated with different comorbidities,
      mainly gastro-oesophageal reflux disease and allergic rhinitis, but also obesity,
      depression, diabetes mellitus and cardiovascular disease, which may affect its
      clinical intensity and severity. The prevalence of these comorbidities varies
      tremendously between studies. Nevertheless, it imposes a significant reflection
      on the need to explore the phenomenon in depth. RECENT FINDINGS: Both clinical
      and basic studies have established that inflammation plays a vital role in the
      initiation and progression of several comorbidities. However, the role of
      systemic inflammation in asthma is still unclear. Understanding mechanism(s) that
      link(s) asthma and its comorbid diseases is essential to design an effective
      therapeutic approach. SUMMARY: In the future, researchers must identify the
      weight of any comorbidity in patients with asthma, find the true mechanism(s)
      that link(s) it to asthma and act on these mechanisms that probably create a
      vicious circle. Conversely, we do not think it reasonable that the generalization
      of treatment with a holistic approach might affect the link(s) between asthma and
      its comorbidities.

PMID- 23114562
TI  - Sleep-disordered breathing and childhood asthma:  clinical implications.
AB  - PURPOSE OF REVIEW: Asthma morbidity in children remains high despite
      comprehensive evidence-based guidelines for evaluation and treatment. The
      objective of this review is to examine the evidence that obstructive sleep
      disordered breathing often co-exists with asthma and is associated with asthma
      severity, and to discuss the clinical implications of this relationship, focusing
      particularly on studies published within the past year. RECENT FINDINGS:
      Obstructive sleep-disordered breathing is highly prevalent in children with
      severe or poorly controlled asthma. Data from an observational study suggest that
      adenotonsillectomy markedly improves asthma outcomes in children with poorly
      controlled asthma and comorbid obstructive sleep apnea. SUMMARY: Clinicians
      should consider evaluating and treating obstructive sleep-disordered breathing in
      children with severe or difficult-to-control asthma. Further controlled studies
      are needed to confirm that treatment of obstructive sleep apnea improves
      pediatric asthma outcomes, and to extend our understanding of how asthma and
      sleep-disordered breathing interact.

PMID- 23114563
TI  - Thermodynamics and solvation dynamics of BIV TAR RNA-Tat peptide interaction.
AB  - The interaction of the trans-activation responsive (TAR) region of bovine
      immunodeficiency virus (BIV) RNA with the Tat peptide is known to play important
      role in viral replication. Despite being thoroughly studied through a structural
      point of view, the nature of binding between BIV TAR RNA and the BIV Tat peptide
      requires information related to its thermodynamics and the nature of hydration
      around the TAR-Tat complex. In this context, we carried out the thermodynamic
      study of binding of the Tat peptide to the BIV TAR RNA hairpin through different
      calorimetric and spectroscopic measurements. Fluorescence titration of 2
      aminopurine tagged BIV TAR RNA with the Tat peptide gives their binding affinity.
      The isothermal titration calorimetric experiment reveals the enthalpy of binding
      between BIV TAR RNA and the Tat peptide to be largely exothermic with the value
      of -11.7 (SEM 0.2) kcal mol(-1). Solvation dynamics measurements of BIV TAR RNA
      having 2-AP located at the bulge region have been carried out in the absence and
      presence of the BIV Tat peptide using the time correlated single photon counting
      technique. The solvent cage around the Tat binding site of RNA appears to be more
      rigid in the presence of the Tat peptide as compared to the free RNA. The
      displacement of solvent and ions on RNA due to peptide binding influences the
      entropic contributions to the total binding energy.

PMID- 23114564
TI  - A person-centered care intervention for geriatric certified nursing assistants.
AB  - PURPOSE: To pilot test a multicomponent intervention to increase certified
      nursing assistants' (CNAs) awareness of person-centered care. To establish the
      feasibility of implementing an intervention involving videotaped biographies of
      residents and videotapes of resident/CNA caregiving interactions. DESIGN AND
      METHODS: A training program was provided at two nursing homes (NHs) using a wait
      list control design. Levels of dyadic relationship closeness and satisfaction
      were compared prepost. Video recordings of CNA/resident interactions were coded
      for person-centered care using two observational instruments. RESULTS: Based on
      data from 19 resident/aide dyads, the findings were that resident's perceptions
      of relationship closeness increased significantly posttraining at both NHs, NH1,
      z = -1.89, p < .05, and the NH2, z = -1.95, p < .05. Effects were also seen with
      the CNA's perceptions of satisfaction and closeness, and resident satisfaction.
      IMPLICATIONS: The findings suggest that this type of intervention is feasible and
      warrants further research.

PMID- 23114565
TI  - Simple and longstanding adipose tissue engineering in rabbits.
AB  - Adipose tissue engineering for breast reconstruction can be performed for
      patients who have undergone breast surgery. We have previously confirmed
      adipogenesis in mice implanted with type I collagen sponge with controlled
      release of fibroblast growth factor 2 (FGF2) and human adipose tissue-derived
      stem cells. However, in order to use this approach to treat breast cancer
      patients, a large amount of adipose tissue is needed, and FGF2 is not readily
      available. Thus, we aimed to regenerate large amounts of adipose tissue without
      FGF2 for a long period. Under general anesthesia, cages made of polypropylene
      mesh were implanted into the rabbits' bilateral fat pads. Each cage was 10 mm in
      radius and 10 mm in height. Minced type I collagen sponge was injected as a
      scaffold into the cage. Regenerated tissue in the cage was examined with
      ultrasonography, and the cages were harvested 3, 6, and 12 months after the
      implantation. Ultrasonography revealed a gradually increasing homogeneous high
      echo area in the cage. Histology of the specimen was assessed with hematoxylin
      and eosin staining. The percentages of regenerated adipose tissue area were 76.2
      +/- 13.0 and 92.8 +/- 6.6 % at 6 and 12 months after the implantation,
      respectively. Our results showed de novo adipogenesis 12 months after the
      implantation of only type I collagen sponge inside the space. Ultrasonography is
      a noninvasive and useful method of assessing the growth of the tissue inside the
      cage. This simple method could be a promising clinical modality in breast
      reconstruction.

PMID- 23114566
TI  - Recognition of emotions in autism: a formal meta-analysis.
AB  - Determining the integrity of emotion recognition in autistic spectrum disorder is
      important to our theoretical understanding of autism and to teaching social
      skills. Previous studies have reported both positive and negative results. Here,
      we take a formal meta-analytic approach, bringing together data from 48 papers
      testing over 980 participants with autism. Results show there is an emotion
      recognition difficulty in autism, with a mean effect size of 0.80 which reduces
      to 0.41 when a correction for publication bias is applied. Recognition of
      happiness was only marginally impaired in autism, but recognition of fear was
      marginally worse than recognition of happiness. This meta-analysis provides an
      opportunity to survey the state of emotion recognition research in autism and to
      outline potential future directions.

PMID- 23114567
TI  - Multisite study of new autism diagnostic interview-revised (ADI-R) algorithms for
      toddlers and young preschoolers.
AB  - Using two independent datasets provided by National Institute of Health funded
      consortia, the Collaborative Programs for Excellence in Autism and Studies to
      Advance Autism Research and Treatment (n = 641) and the National Institute of
      Mental Health (n = 167), diagnostic validity and factor structure of the new
      Autism Diagnostic Interview (ADI-R) algorithms for toddlers and young
      preschoolers were examined as a replication of results with the 2011 Michigan
      sample (Kim and Lord in J Autism Dev Disord 42(1): 82-93, 2012). Sensitivities
      and specificities and a three-factor solution were replicated. Results suggest
      that the new ADI-R algorithms can be appropriately applied to existing research
      databases with children from 12 to 47 months and down to nonverbal mental ages of
      10 months for diagnostic grouping.

PMID- 23114568
TI  - Linguistic alignment in adults with and without Asperger's syndrome.
AB  - Individuals with Asperger's syndrome (AS) often have difficulties with social
      interactions and conversations. We investigated if these difficulties could be
      attributable to a deficit in the ability to linguistically converge with an
      interlocutor, which is posited to be important for successful communication. To
      that end, participants completed two cooperative tasks with a confederate, which
      allowed us to measure linguistic alignment with the confederate in terms of
      lexical choice, syntactic structure and spatial frame of reference. There was no
      difference in the performance of individuals with AS and matched controls and
      both groups showed significant alignment with the confederate at all three
      levels. We conclude that linguistic alignment is intact in adults with AS engaged
      in structured, goal-directed social interactions.

PMID- 23114569
TI  - Science, technology, engineering, and mathematics (STEM) participation among
      college students with an autism spectrum disorder.
AB  - Little research has examined the popular belief that individuals with an autism
      spectrum disorder (ASD) are more likely than the general population to gravitate
      toward science, technology, engineering, and mathematics (STEM) fields. This
      study analyzed data from the National Longitudinal Transition Study-2, a
      nationally representative sample of students with an ASD in special education.
      Findings suggest that students with an ASD had the highest STEM participation
      rates although their college enrollment rate was the third lowest among 11
      disability categories and students in the general population. Disproportionate
      postsecondary enrollment and STEM participation by gender, family income, and
      mental functioning skills were found for young adults with an ASD. Educational
      policy implications are discussed.

PMID- 23114570
TI  - Silver-catalyzed silicon-hydrogen bond functionalization by carbene insertion.
AB  - The catalytic functionalization of silicon-hydrogen bonds by means of the
      insertion of carbene units :CHCO(2)Et from ethyl diazoacetate (EDA) has been
      achieved using a silver-based catalyst, constituting the first example of this
      metal to promote this transformation. Competition experiments have revealed that
      the relative reactivity of substituted silanes depends on the bond dissociation
      energy of the Si-H bond (tertiary > secondary > primary for ethyl substituted).
      In the presence of bulky substituents such order reverts to secondary > primary ~
      tertiary (for phenyl substituted). Screening with other diazo compounds has shown
      that N(2)C(Ph)CO(2)Et displays similar reactivity to that of EDA, whereas other
      N(2)C(R)CO(2)Et (R = Me, CO(2)Et) gave lower conversions.

PMID- 23114571
TI  - Actinoplanes hulinensis sp. nov., a novel actinomycete isolated from soybean root
      (Glycine max (L.) Merr).
AB  - A novel actinomycete, designated strain NEAU-M9(T), was isolated from soybean
      root (Glycine max (L.) Merr) and characterized using a polyphasic approach. 16S
      rRNA gene sequence similarity studies showed that strain NEAU-M9(T) belonged to
      the genus Actinoplanes, being most closely related to Actinoplanes campanulatus
      DSM 43148(T) (98.85 %), Actinoplanes capillaceus DSM 44859(T) (98.70 %),
      Actinoplanes lobatus DSM 43150(T) (98.30 %), Actinoplanes auranticolor DSM
      43031(T) (98.23 %) and Actinoplanes sichuanensis 03-723(T) (98.06 %); similarity
      to other type strains of the genus Actinoplanes ranged from 95.87 to 97.56 %. The
      neighbour-joining phylogenetic tree based on 16S rRNA gene sequences showed that
      the isolate formed a distinct phyletic line with A. campanulatus DSM 43148(T) and
      A. capillaceus DSM 44859(T). This branching pattern was also supported by the
      tree constructed with the maximum-likelihood method. However, the low level of
      DNA-DNA relatedness allowed the isolate to be differentiated from the above
      mentioned two Actinoplanes species. Moreover, strain NEAU-M9(T) could also be
      distinguished from the most closely related species by morphological,
      physiological and characteristics. Therefore, it is proposed that strain NEAU
      M9(T) represents a novel Actinoplanes species, Actinoplanes hulinensis sp. nov.
      The type strain of Actinoplanes hulinensis is NEAU-M9(T) (= CGMCC 4.7036(T) = DSM
      45728(T)).

PMID- 23114573
TI  - Detection of yeast species also occurring in substrates associated with animals
      and identification of a novel dimorphic species in Verbascum flowers from
      Georgia.
AB  - The molecular taxonomic analysis of yeasts isolated from Verbascum flowers
      collected in central Georgia identified strains that could be assigned to the
      species Cryptococcus adeliensis, Cryptococcus magnus and Moniliella
      megachiliensis detected previously also in substrates associated with insects and
      other animals and a hitherto undescribed species for which the name Candida
      verbasci is proposed. The new species forms slightly pink colonies, propagates by
      mostly unipolar budding, forms invasive pseudomycelium, and the sequences of its
      D1/D2 LSU rRNA genes and ITS1-5.8S-ITS2 regions indicate close phylogenetic
      relationship with a group of species that form a cluster basal to the Candida
      albicans/Lodderomyces elongisporus clade. The type strain is 11-1055(T). It has
      been deposited in Centralbureau voor Schimmelcultures (Utrecht, the Netherlands)
      as CBS 12699(T), the National Collection of Agricultural and Industrial
      Microorganisms (Budapest, Hungary) as NCAIM Y.02048(T) and the Culture Collection
      of Yeasts (Bratislava, Slovakia) as CCY 29-185-1(T). The GenBank accession
      numbers for nucleotide sequences of the C. verbasci type strain are: JX515981
      (D1/D2 domain of the 26S rRNA gene) and JX515982 (ITS1-5.8S-ITS2). Mycobank: MB
      801391.

PMID- 23114575
TI  - Multiple phenological responses to climate change among 42 plant species in
      Xi'an, China.
AB  - Phenological data of 42 woody plants in a temperate deciduous forest from the
      Chinese Phenological Observation Network (CPON) and the corresponding
      meteorological data from 1963 to 2011 in Xi'an, Shaanxi Province, China were
      collected and analyzed. The first leaf date (FLD), leaf coloring date (LCD) and
      first flower date (FFD) are revealed as strong biological signals of climatic
      change. The FLD, LCD and FFD of most species are sensitive to average temperature
      during a certain period before phenophase onset. Regional precipitation also has
      a significant impact on phenophases of about half of the species investigated.
      Affected by climate change, the FLD and FFD of these species have advanced by
      5.54 days and 10.20 days on average during 2003-2011 compared with the period
      1963-1996, respectively. Meanwhile, the LCD has delayed by 10.59 days, and
      growing season length has extended 16.13 days. Diverse responses of phenology
      commonly exist among different species and functional groups during the study
      period. Especially for FFD, the deviations between the above two periods ranged
      from -20.68 to -2.79 days; biotic pollination species showed a significantly
      greater advance than abiotic pollination species. These results were conducive to
      the understanding of possible changes in both the structure of plant communities
      and interspecific relationships in the context of climate change. 

PMID- 23114574
TI  - The relationship between pneumatized middle turbinate and the anterior ethmoid
      roof dimensions: a radiologic study.
AB  - The development of pneumatized middle turbinate may affect anterior ethmoid roof
      formation. The aim of this study was to investigate the relationship between the
      pneumatized middle turbinate and the dimensions of the anterior skull base
      structures using computed tomography scans. The coronal reconstructed images of
      the computed tomography scans were evaluated retrospectively. The lateral and
      medial ethmoid roof points, the width of the cribriform plate (CP), and the
      anterior ethmoid roof were identified at the first coronal cut, which was
      determined by the infraorbital nerve. The pneumatized middle turbinates were
      measured on the axial, vertical, and sagittal planes. The images of 101 patients
      were evaluated. The mean axial diameters of the pneumatized middle turbinate on
      the right and left sides were between 6.93 and 4.95 mm, respectively. The
      correlation between the axial diameters of the pneumatized middle turbinate and
      the width of the anterior ethmoid roof (termed AER width) was significant for
      both sides and gender (p < 0.05). There was a higher correlation on the right
      side where the pneumatized middle turbinate was observed more frequently (r =
      0.357). The relationship between CP width and the diameters of the pneumatized
      middle turbinate was not significant (p > 0.05) for both sides. Iatrogenic
      lesions of the skull base occur predominantly in the lateral lamella of the CP.
      The risk of this complication may decrease with increasing of the AER width.
      Pneumatized middle turbinate may cause an increase in the width of the anterior
      ethmoid roof and provide more reliable endoscopic intervention of the anterior
      skull base and frontal sinus.

PMID- 23114577
TI  - Morphological characterization of Pelibuey sheep in Colima, Mexico.
AB  - A study was conducted with the objective to characterize the morphology of
      Pelibuey sheep in the state of Colima, Mexico. A total of 386 sheep were scored
      for 12 body measurements in addition to live weight and five racial and eight
      functional indices were calculated. The influence of sex on the body measurements
      and indices was analyzed, and morphological harmony was determined through
      Pearson correlation. The sexual dimorphism was 1.21, with males being 67 %
      heavier than females. Females and males had a high and moderate degree of harmony
      in their morphological model, respectively. Pelibuey sheep were dolichocephalous,
      tended to be medium- to large-sized according to the thoracic index, with a
      convex curve rump; they were a homogeneous breed, well adapted to environmental
      and production conditions of the state of Colima, Mexico, and show an undefined
      zootechnical aptitude and therefore a great potential to be oriented towards meat
      or milk production through genetic selection or terminal crossbreeding systems
      using specialized breeds.

PMID- 23114579
TI  - Invasive stimulation therapies for the treatment of refractory pain.
AB  - Invasive neurostimulation therapies may be proposed to patients with neuropathic
      pain refractory to conventional medical management, in order to improve pain
      relief, functional capacity, and quality of life. In this review, the respective
      mechanisms of action and efficacy of peripheral nerve stimulation (PNS), nerve
      root stimulation (NRS), spinal cord stimulation (SCS), deep brain stimulation
      (DBS), and motor cortex stimulation (MCS) are discussed. PNS appears to be useful
      in various refractory neuropathic pain indications (as long as there is some
      preservation of sensation in the painful area), such as intractable chronic
      headache, pelvic and perineal pain, and low back pain, but evidence for its
      efficacy is not strongly conclusive, and large-scale randomized controlled
      studies are necessary to confirm the efficacy in the long term. Spinal cord
      stimulation (SCS) has been validated for the treatment of selected types of
      chronic pain syndromes, such as Failed Back Surgery Syndrome, and Complex
      Regional Pain Syndrome type I. When neuropathic pain is secondary to a brain
      lesion (especially following stroke) or a trigeminal lesion, stimulation of brain
      structures is required. Deep brain stimulation (DBS), which can be proposed with
      targets like the periventricular/periaqueductal gray matter or the sensory
      thalamus, is increasingly replaced by motor cortex stimulation (MCS), mainly
      because it is safer, more easily performed, and probably more effective in a
      wider range of indications (including central post-stroke pain). The respective
      places of DBS and MCS in some selected indications, such as peripheral
      neuropathic pain and phantom limb pain, have yet to be clearly delineated.
      Controlled trials, with the stimulator switched ON or OFF in a double-blind
      procedure, have demonstrated the efficacy of MCS in the treatment of peripheral
      and central neuropathic pain, although these trials included a limited number of
      patients and need to be confirmed by large, controlled, multicenter studies.
      Despite technical progress in neurosurgical navigation, guided by neuroimaging
      and intraoperative electrophysiology to optimize electrode positioning, MCS
      results are still variable, and validated criteria for selecting good candidates
      for implantation are lacking, except clinical response to preoperative rTMS,
      which showed correlations with a good response to MCS-induced analgesia. However,
      the evidence in favor of this technique is sufficient to include it in the range
      of treatment options for refractory neuropathic pain.

PMID- 23114578
TI  - T cell coinhibition and immunotherapy in human breast cancer.
AB  - Costimulation and coinhibition generated by the B7 family and their receptor CD28
      family have key roles in regulating T lymphocyte activation and tolerance. These
      pathways are very attractive therapeutic targets for human cancers including
      breast cancer. Gene polymorphisms of B7x (B7-H4/B7S1), PD-1 (CD279), and CTLA-4
      (CD152) are associated with increased risk of developing breast cancer although
      the underlying mechanisms are unclear. In human breast cancer microenvironment,
      up-regulation of coinhibitory B7/CD28 members B7x, B7-H3 (CD276), and PD-L1 (B7
      H1/CD274) on tumor cells as well as PD-1 and PD-L1 on tumor-infiltrating immune
      cells are emerging as immune evasion pathways. Chemotherapy can affect the
      expression of these molecules, and therefore may dampen the immune response
      against breast cancer. Immunotherapy targeting T cell coinhibition as monotherapy
      or combined with standard therapies are in early stages of clinical development,
      but hold great promise for treatment of human breast cancer.

PMID- 23114580
TI  - Exercise testing in the 21st century: from an "old" diagnostic to a novel health
      risk assessment tool.
AB  - Exercise testing was developed as a diagnostic tool in the first half of the 20th
      century when people, mostly men, paid the huge cost of coronary artery disease
      (CAD). Both the changing nature of CAD, which affects both men and women, and the
      aging of the population led to redefining the use of exercise testing. This test
      is now mainly used for evaluating overall prognosis. In parallel, new measurement
      such as exercise capacity and several components of the physiological reserve
      enrich the information which can be obtained from exercise testing. Therefore,
      exercise testing has become the major dynamic tool for predicting premature
      mortality far beyond traditional and disease specific risk markers. The present
      article reviews the main pieces of information which led to these changes and
      summarizes the elements which give exercise testing its utility.

PMID- 23114581
TI  - Role of the IL-23/IL-17 axis in Crohn's disease.
AB  - Crohn's disease is an immune-mediated disease that is characterized by chronic
      intestinal inflammation. Effector CD4+ T-lymphocytes are expanded in Crohn's
      disease-associated inflammatory lesions and play a critical role in the
      pathogenesis of this condition. Recently, a novel population of effector T
      lymphocytes has been identified, which is clearly separated from the traditional
      Th1 and Th2 lineages and is characterized by the secretion of IL-17, hence its
      designation as Th17. The development of this population has been closely linked
      to IL-23, a member of the IL-12 family of cytokines. Converging lines of evidence
      support the hypothesis that the IL-23/Th17 axis is of pathogenic relevance for
      Crohn's disease. Protein and mRNA levels of IL-23, IL-17, and other Th17 effector
      cytokines, such as IL-21 and IL-22, are elevated in areas with active Crohn's
      disease-related inflammation, whereas lamina propria mononuclear cells from
      patients with Crohn's disease secrete increased amounts of IL-17 upon T-cell
      receptor-specific stimulation. Genome-wide association studies have identified
      several Crohn's disease-associated polymorphisms in genes that encode for
      proteins of the IL-23/Th17 pathway. Functional studies have shown that Th17
      related effector cytokines induce pro-inflammatory responses that are components
      of the pathogenetic mechanisms of Crohn's disease, including recruitment of
      neutrophils via IL-8 induction, upregulation of inflammatory mediators such as
      TNF-alpha, IL-1beta, and IL-6, and secretion of metalloproteinases by intestinal
      fibroblasts. Finally, in several animal models of intestinal inflammation,
      disease severity is ameliorated when the IL-23/Th17 pathway is rendered
      deficient. These findings point to a critically important role for IL-23/Th17
      mediated immune responses in Crohn's disease pathogenesis and may offer unique
      therapeutic opportunities for patients.

PMID- 23114582
TI  - Seeking synergy in p53 transcriptional activation for cancer therapy.
AB  - Targeting the p53-MDM2 pathway is regarded as a viable therapeutic strategy and
      is supported by several preclinical mouse models which show that the restoration
      of p53 activity leads to tumor regression in vivo. Given that a large proportion
      of cancers, including hematological malignancies, retain the expression of the
      wildtype p53 allele, reactivating wildtype p53 in these cancers could lead to
      selective apoptosis and is regarded as a potential therapeutic strategy. The
      exploration of inhibitors and peptides targeting the p53-MDM2 pathway led to the
      discoveries of specific small molecule inhibitors that disrupt the MDM2-mediated
      inhibition of p53 transcriptional activity and protein stability. Nutlin is one
      of the specific small molecule that is well tolerated in vivo in mice but has
      been used in combinations with conventional chemotherapy and radiotherapy, as
      well as molecularly targeted drugs to further increase its specificity and
      potency in vivo. We attempt to identify pathways or new targets which when
      inhibited may synergize with nutlin in its activation of p53 transcriptional
      activity. Our previous results show that CDK inhibition synergizes with nutlin in
      p53 activation and p53-dependent apoptosis, converting a cell cycle arrest
      response to apoptosis. Here, using a siRNA screen against 726 human kinases, we
      identified several pathways, including the MAP kinase pathway, the sphingosine
      kinase pathway, and the CDK pathway which may have crosstalk with the p53
      pathway. Selective inhibition of these pathways may synergize with nutlin in the
      induction of p53 transcriptional activity.

PMID- 23114584
TI  - Chemical-induced DNA damage and human cancer risk.
AB  - For more than 200 years human cancer induction has been known to be associated
      with a large variety of chemical exposures. Most exposures to chemical
      carcinogens occur as a result of occupation, pollution in the ambient
      environment, lifestyle choices, or pharmaceutical use. Scientific investigations
      have revealed that the majority of cancer causing chemicals, or chemical
      carcinogens, act through "genotoxic" or DNA damaging mechanisms, which involve
      covalent binding of the chemical to DNA (DNA adduct formation). Cancer-inducing
      exposures are typically frequent and/or chronic over years, and the accumulation
      of DNA damage or DNA adduct formation is considered to be a necessary requirement
      for tumor induction. Studies in animal models have indicated that the ability to
      reduce DNA damage will also result in reduction of tumor risk, leading to the
      hypothesis that individuals having the highest levels of DNA adducts may have an
      increased cancer risk, compared to individuals with the lowest levels of DNA
      adducts. Here we have reviewed twelve investigations showing 2- to 9-fold
      increased Relative Risks (RR) or Odds Ratios (OR) for cancer in (the 25% of)
      individuals having the highest DNA adduct levels, compared to (the 25% of)
      matched individuals with the lowest DNA adducts. These studies also provided
      preliminary evidence that multiple types of DNA adducts combined, or DNA adducts
      combined with other risk factors (such as infection or inflammation), may be
      associated with more than 10-fold higher cancer risks (RR = 34-60), compared to
      those found with a single carcinogen. Taken together the data suggest that a
      reduction in human DNA adduct level is likely to produce a reduction in human
      cancer risk.

PMID- 23114583
TI  - Gaucher disease: insights from a rare Mendelian disorder.
AB  - It has become increasingly clear that "simple" recessive disorders provide unique
      insight into the complexities of common diseases. For years, research on Gaucher
      disease, a rare inherited disorder resulting from a deficiency of the lysosomal
      enzyme glucocerebrosidase, focused on its cell pathology and genetic basis.
      Clinical research showed that Gaucher disease manifests with broad phenotypic
      variation typical of many metabolic disorders, ranging from neonatal lethality to
      asymptomatic octogenarians. This clinical spectrum now overlaps with different
      disorders including Parkinson's disease and other Lewy body disorders, myoclonic
      epilepsy, and infantile neurodegenerative disorders. In fact, unraveling the
      factors contributing to heterogeneity in a single gene disorder may have a direct
      impact on studies of the pathophysiology and therapeutic options available for
      these more common and complex neurologic diseases.

PMID- 23114585
TI  - New treatment strategies in large-vessel vasculitis.
AB  - PURPOSE OF REVIEW: Recent advancements in the understanding of the pathogenesis
      of large-vessel vasculitis may broaden our currently limited therapeutic
      possibilities. This review summarizes the available evidence for new treatment
      strategies in this spectrum of diseases. RECENT FINDINGS: Interleukin (IL) 6
      appears to be an important mediator of the pathology in large-vessel vasculitis.
      IL-6 is upregulated in inflamed arteries of patients with giant cell arteritis
      and Takayasu arteritis, and serum levels of this cytokine mirror disease
      activity. Encouraging preliminary results have been obtained with the IL-6
      receptor (IL-6R) antagonist tocilizumab for the treatment of large-vessel
      vasculitides, including both giant cell arteritis and Takayasu arteritis, and the
      aortitis of Cogan syndrome and relapsing polychondritis. A small number of
      patients with Takayasu arteritis and IgG4-related aortitis have also been
      successfully treated with the B-cell depleting agent rituximab, and some patients
      with refractory Takayasu arteritis have responded to the immunomodulator
      leflunomide. SUMMARY: The possibility of biologic therapy in large vessel
      vasculitis has emerged. At this time, better delineation of the immunopathogenic
      mechanisms of this spectrum of diseases and prospective randomized clinical
      trials are required to move the field forward and decrease the cumulative
      glucocorticoid toxicity seen in these disorders.

PMID- 23114586
TI  - Myofibroblasts.
AB  - PURPOSE OF REVIEW: Interest in the myofibroblast as a key player in propagation
      of chronic progressive fibrosis continues to elicit many publications, with focus
      on its cellular origins and the mechanisms underpinning their differentiation
      and/or transition. The objective of the review is to highlight this recent
      progress. RECENT FINDINGS: The epithelial origin of the myofibroblast in fibrosis
      has been challenged by recent studies, with the pericyte suggested as a possible
      precursor instead. Additional signaling pathways, including Notch, Wnt, and
      hedgehog, are implicated in myofibroblast differentiation. The importance of
      NADPH oxidase 4 was highlighted recently to suggest a potential link between
      cellular/oxidative stress and the genesis of the myofibroblast. Recent
      observations on the importance of lysophosphatidic acid in fibrosis suggest that
      this may be due, in part, to its ability to regulate myofibroblast
      differentiation. Finally, there is increasing evidence for the role of epigenetic
      mechanisms in regulating myofibroblast differentiation, including DNA methylation
      and miRNA regulation of gene expression. SUMMARY: These recent discoveries open
      up a whole new array of potential targets for novel antifibrotic therapies. This
      is of special importance given the current bleak outlook for chronic progressive
      fibrotic diseases, such as scleroderma, due to lack of effective therapies.

PMID- 23114587
TI  - Biologics-induced autoimmune diseases.
AB  - PURPOSE OF REVIEW: Biological agents are therapies designed to target a specific
      molecular component of the immune system, and are currently licensed for use in
      autoimmune rheumatic, digestive, dermatological and systemic diseases. However,
      their use has been linked with the paradoxical development of autoimmune
      processes. RECENT FINDINGS: More than 1500 cases of autoimmune diseases induced
      by biologics have been reported, including a wide variety of both systemic
      (lupus, vasculitis, sarcoidosis, antiphospholipid syndrome and inflammatory
      myopathies) and organ-specific (interstitial lung disease, uveitis, optic
      neuritis, peripheral neuropathies, multiple sclerosis, psoriasis, inflammatory
      bowel disease and autoimmune hepatitis) autoimmune processes. Although these
      processes are overwhelmingly associated with anti-TNF agents, recent cases have
      been associated with therapies directed against other cytokines, B or T-cells,
      illustrating that even though targeting a particular immune molecule may be
      associated with an excellent clinical response in most patients, an unexpected
      autoimmune response may arise in some cases. SUMMARY: As the use of biological
      therapies expands, the number and diversity of induced autoimmune disorders
      should be expected to increase. Paradoxically, for many of these drug-related
      processes, current treatment indications include the very biological agent
      producing the adverse event.

PMID- 23114588
TI  - Angiogenesis and scar formation in healing wounds.
AB  - PURPOSE OF REVIEW: One well described feature of wound healing is the ingrowth of
      new capillaries or angiogenesis. At its peak, the capillary content in healing
      wounds may reach three or more times that of normal uninjured tissue. This new
      vasculature is required to restore oxygenation and allow the growth of new tissue
      to fill the wound space. This review examines the assumption that a capillary
      content in excess of normal density is essential for adequate healing. RECENT
      FINDINGS: The regulation of wound angiogenesis has been demonstrated to involve
      both proangiogenic and antiangiogenic stimuli, with the level of capillary growth
      reliant upon both sets of factors. Several studies now show that normal skin
      wounds heal adequately even when the angiogenic response is artificially reduced.
      In normal skin, a reduction of capillary growth to a level consistent with normal
      tissue does not affect wound closure and may even lead to highly favorable long
      term healing outcomes. SUMMARY: The angiogenic response in normal wounds may
      exceed what is needed for optimal repair.

PMID- 23114589
TI  - Biomechanical regulation of mesenchymal cell function.
AB  - PURPOSE OF REVIEW: Cells of mesenchymal origin are strongly influenced by their
      biomechanical environment. They also help to shape tissue architecture and
      reciprocally influence tissue mechanical environments through their capacity to
      deposit, remodel, and resorb extracellular matrix and to promote tissue
      vascularization. Although mechanical regulation of cell function and tissue
      remodeling has long been appreciated in other contexts, the purpose of this
      review is to highlight the increasing appreciation of its importance in fibrosis
      and hypertrophic scarring. RECENT FINDINGS: Experiments in both animal and
      cellular model systems have demonstrated pivotal roles for the biomechanical
      environment in regulating myofibroblast differentiation and contraction,
      endothelial barrier function and angiogenesis, and mesenchymal stem cell fate
      decisions. Through these studies, a better understanding of the molecular
      mechanisms transducing the biomechanical environment is emerging, with prominent
      and interacting roles recently identified for key network components including
      transforming growth factor-beta/SMAD, focal adhesion kinase, MRTFs, Wnt/beta
      catenin and YAP/TAZ signaling pathways. SUMMARY: Progress in understanding
      biomechanical regulation of mesenchymal cell function is leading to novel
      approaches for improving clinical outcomes in fibrotic diseases and wound
      healing. These approaches include interventions aimed at modifying the tissue
      biomechanical environment, and efforts to target mesenchymal cell activation by,
      and reciprocal interactions with, the mechanical environment.

PMID- 23114590
TI  - Epigenetic regulation of wound healing and fibrosis.
AB  - PURPOSE OF REVIEW: Wound healing is a normal physiological response to tissue
      injury which can occur in any organ. Mechanisms that orchestrate wound healing in
      different organs are surprisingly generic, involving generation of fibroblasts
      and myofibroblasts by differentiation processes that require extensive
      alterations in gene expression. This process and indeed phenotype of cells are
      orchestrated by the combined influences of molecular components of epigenome
      including DNA methylation, vast array of posttranslational modifications of the
      histone protein constituents of chromatin and regulatory noncoding RNAs of which
      microRNAs (miRs) are the most extensively studied. RECENT FINDINGS: Numerous
      studies from the last 12 months show all the three epigenetic mechanisms to be
      regulating generation and apoptosis of myofibroblasts in organs affected by
      perturbed wound healing. Furthermore, these mechanisms are involved in fibrotic
      disease itself, with some miRs and epigenetic drugs being tested for their
      therapeutic potential. SUMMARY: Fields of wound healing and fibrosis will be
      enriched over the next decade by plethora of new information regarding epigenetic
      control mechanisms which will hopefully provide new advances in diagnostics and
      prognostics. With the design of ever more specific epigenetic drugs, we may
      improve our ability to therapeutically optimize wound healing and prevent
      fibrosis in chronic disease and ageing.

PMID- 23114593
TI  - Spinning motion of a deformable self-propelled particle in two dimensions.
AB  - We investigate the dynamics of a single deformable self-propelled particle which
      undergoes a spinning motion in a two-dimensional space. Equations of motion are
      derived from symmetry arguments for three kinds of variable. One is a vector
      which represents the velocity of the center of mass. The second is a traceless
      symmetric tensor representing deformation. The third is an antisymmetric tensor
      for spinning degree of freedom. By numerical simulations, we have obtained a
      variety of dynamical states due to interplay between the spinning motion and the
      deformation. The bifurcations of these dynamical states are analyzed by the
      simplified equations of motion.

PMID- 23114592
TI  - Role of phosphodiesterase-5 inhibitors in heart failure: emerging data and
      concepts.
AB  - Novel treatment of congestive heart failure (HF) involves utilizing unique
      pathways to improve upon contemporary therapies. Increasing the availability of
      cyclic guanosine monophosphate (cGMP) by inhibition of phosphodiesterase-5 (PDE5)
      is a relatively new, but promising therapeutic strategy. Preclinical studies
      suggest a favorable myocardial effect of PDE5 inhibitors by blocking adrenergic,
      hypertrophic and pro-apoptotic signaling, thereby supporting their use in HF. The
      clinical benefits of acute and chronic PDE5 inhibition on lung diffusion
      capacity, exercise performance and ejection fraction in humans are emerging and
      appear promising. Larger, controlled trials are now on-going to assess the
      safety, efficacy and tolerability of PDE5 inhibitors on morbidity and mortality
      in patients with both systolic and diastolic heart failure. If the results of
      these trials are positive, a new avenue for the treatment of HF will open, which
      will help curtail the societal effects of this costly and morbid disease.

PMID- 23114591
TI  - Mineralocorticoid receptor antagonism confers cardioprotection in heart failure.
AB  - The symptoms and signs constituting the congestive heart failure (CHF) syndrome
      have their pathophysiologic origins rooted in a salt-avid renal state mediated by
      effector hormones of the renin-angiotensin-aldosterone and adrenergic nervous
      systems. Controlled clinical trials, conducted over the past decade in patients
      having minimally to markedly severe symptomatic heart failure, have demonstrated
      the efficacy of a pharmacologic regimen that interferes with these hormones,
      including aldosterone receptor binding with either spironolactone or eplerenone.
      Potential pathophysiologic mechanisms, which have not hitherto been considered
      involved for the salutary responses and cardioprotection provided by these
      mineralocorticoid receptor antagonists, are reviewed herein. In particular, we
      focus on the less well-recognized impact of catecholamines and aldosterone on
      monovalent and divalent cation dyshomeostasis, which leads to hypokalemia,
      hypomagnesemia, ionized hypocalcemia with secondary hyperparathyroidism and
      hypozincemia. Attendant adverse cardiac consequences include a delay in
      myocardial repolarization with increased propensity for supraventricular and
      ventricular arrhythmias, and compromised antioxidant defenses with increased
      susceptibility to nonischemic cardiomyocyte necrosis.

PMID- 23114594
TI  - DGAT1 mutation is linked to a congenital diarrheal disorder.
AB  - Congenital diarrheal disorders (CDDs) are a collection of rare, heterogeneous
      enteropathies with early onset and often severe outcomes. Here, we report a
      family of Ashkenazi Jewish descent, with 2 out of 3 children affected by CDD.
      Both affected children presented 3 days after birth with severe, intractable
      diarrhea. One child died from complications at age 17 months. The second child
      showed marked improvement, with resolution of most symptoms at 10 to 12 months of
      age. Using exome sequencing, we identified a rare splice site mutation in the
      DGAT1 gene and found that both affected children were homozygous carriers.
      Molecular analysis of the mutant allele indicated a total loss of function, with
      no detectable DGAT1 protein or activity produced. The precise cause of diarrhea
      is unknown, but we speculate that it relates to abnormal fat absorption and
      buildup of DGAT substrates in the intestinal mucosa. Our results identify DGAT1
      loss-of-function mutations as a rare cause of CDDs. These findings prompt concern
      for DGAT1 inhibition in humans, which is being assessed for treating metabolic
      and other diseases.

PMID- 23114595
TI  - Gain of glycosylation in integrin alpha3 causes lung disease and nephrotic
      syndrome.
AB  - Integrins are transmembrane alphabeta glycoproteins that connect the
      extracellular matrix to the cytoskeleton. The laminin-binding integrin
      alpha3beta1 is expressed at high levels in lung epithelium and in kidney
      podocytes. In podocytes, alpha3beta1 associates with the tetraspanin CD151 to
      maintain a functional filtration barrier. Here, we report on a patient homozygous
      for a novel missense mutation in the human ITGA3 gene, causing fatal interstitial
      lung disease and congenital nephrotic syndrome. The mutation caused an alanine-to
      serine substitution in the integrin alpha3 subunit, thereby introducing an N
      glycosylation motif at amino acid position 349. We expressed this mutant form of
      ITGA3 in murine podocytes and found that hyperglycosylation of the alpha3
      precursor prevented its heterodimerization with beta1, whereas CD151 association
      with the alpha3 subunit occurred normally. Consequently, the beta1 precursor
      accumulated in the ER, and the mutant alpha3 precursor was degraded by the
      ubiquitin-proteasome system. Thus, these findings uncover a gain-of-glycosylation
      mutation in ITGA3 that prevents the biosynthesis of functional alpha3beta1,
      causing a fatal multiorgan disorder.

PMID- 23114596
TI  - Compromised genomic integrity impedes muscle growth after Atrx inactivation.
AB  - ATR-X syndrome is a severe intellectual disability disorder caused by mutations
      in the ATRX gene. Many ancillary clinical features are attributed to CNS
      deficiencies, yet most patients have muscle hypotonia, delayed ambulation, or
      kyphosis, pointing to an underlying skeletal muscle defect. Here, we identified a
      cell-intrinsic requirement for Atrx in postnatal muscle growth and regeneration
      in mice. Mice with skeletal muscle-specific Atrx conditional knockout (Atrx cKO
      mice) were viable, but by 3 weeks of age presented hallmarks of underdeveloped
      musculature, including kyphosis, 20% reduction in body mass, and 34% reduction in
      muscle fiber caliber. Atrx cKO mice also demonstrated a marked regeneration
      deficit that was not due to fewer resident satellite cells or their inability to
      terminally differentiate. However, activation of Atrx-null satellite cells from
      isolated muscle fibers resulted in a 9-fold reduction in myoblast expansion,
      caused by delayed progression through mid to late S phase. While in S phase, Atrx
      colocalized specifically to late-replicating chromatin, and its loss resulted in
      rampant signs of genomic instability. These observations support a model in which
      Atrx maintains chromatin integrity during the rapid developmental growth of a
      tissue.

PMID- 23114597
TI  - Inflammatory arthritis increases mouse osteoclast precursors with myeloid
      suppressor function.
AB  - Increased osteoclastic bone resorption leads to periarticular erosions and
      systemic osteoporosis in RA patients. Although a great deal is known about how
      osteoclasts differentiate from precursors and resorb bone, the identity of an
      osteoclast precursor (OCP) population in vivo and its regulatory role in RA
      remains elusive. Here, we report the identification of a CD11b(-/lo)Ly6C(hi) BM
      population with OCP activity in vitro and in vivo. These cells, which can be
      distinguished from previously characterized precursors in the myeloid lineage,
      display features of both M1 and M2 monocytes and expand in inflammatory arthritis
      models. Surprisingly, in one mouse model of RA (adoptive transfer of SKG
      arthritis), cotransfer of OCP with SKG CD4+ T cells diminished inflammatory
      arthritis. Similar to monocytic myeloid-derived suppressor cells (M-MDSCs), OCPs
      suppressed CD4+ and CD8+ T cell proliferation in vitro through the production of
      NO. This study identifies a BM myeloid precursor population with osteoclastic and
      T cell-suppressive activity that is expanded in inflammatory arthritis.
      Therapeutic strategies that prevent the development of OCPs into mature bone
      resorbing cells could simultaneously prevent bone resorption and generate an
      antiinflammatory milieu in the RA joint.

PMID- 23114598
TI  - Hypoxia-inducible factor regulates hepcidin via erythropoietin-induced
      erythropoiesis.
AB  - Iron demand in bone marrow increases when erythropoiesis is stimulated by hypoxia
      via increased erythropoietin (EPO) synthesis in kidney and liver. Hepcidin, a
      small polypeptide produced by hepatocytes, plays a central role in regulating
      iron uptake by promoting internalization and degradation of ferroportin, the only
      known cellular iron exporter. Hypoxia suppresses hepcidin, thereby enhancing
      intestinal iron uptake and release from internal stores. While HIF, a central
      mediator of cellular adaptation to hypoxia, directly regulates renal and hepatic
      EPO synthesis under hypoxia, the molecular basis of hypoxia/HIF-mediated hepcidin
      suppression in the liver remains unclear. Here, we used a genetic approach to
      disengage HIF activation from EPO synthesis and found that HIF-mediated
      suppression of the hepcidin gene (Hamp1) required EPO induction. EPO induction
      was associated with increased erythropoietic activity and elevated serum levels
      of growth differentiation factor 15. When erythropoiesis was inhibited
      pharmacologically, Hamp1 was no longer suppressed despite profound elevations in
      serum EPO, indicating that EPO by itself is not directly involved in Hamp1
      regulation. Taken together, we provide in vivo evidence that Hamp1 suppression by
      the HIF pathway occurs indirectly through stimulation of EPO-induced
      erythropoiesis.

PMID- 23114600
TI  - Natriuretic peptides enhance the oxidative capacity of human skeletal muscle.
AB  - Cardiac natriuretic peptides (NP) are major activators of human fat cell
      lipolysis and have recently been shown to control brown fat thermogenesis. Here,
      we investigated the physiological role of NP on the oxidative metabolism of human
      skeletal muscle. NP receptor type A (NPRA) gene expression was positively
      correlated to mRNA levels of PPARgamma coactivator-1alpha (PGC1A) and several
      oxidative phosphorylation (OXPHOS) genes in human skeletal muscle. Further, the
      expression of NPRA, PGC1A, and OXPHOS genes was coordinately upregulated in
      response to aerobic exercise training in human skeletal muscle. In human
      myotubes, NP induced PGC-1alpha and mitochondrial OXPHOS gene expression in a
      cyclic GMP-dependent manner. NP treatment increased OXPHOS protein expression,
      fat oxidation, and maximal respiration independent of substantial changes in
      mitochondrial proliferation and mass. Treatment of myotubes with NP recapitulated
      the effect of exercise training on muscle fat oxidative capacity in vivo.
      Collectively, these data show that activation of NP signaling in human skeletal
      muscle enhances mitochondrial oxidative metabolism and fat oxidation. We propose
      that NP could contribute to exercise training-induced improvement in skeletal
      muscle fat oxidative capacity in humans.

PMID- 23114599
TI  - The NF-kappaB regulator MALT1 determines the encephalitogenic potential of Th17
      cells.
AB  - Effector functions of inflammatory IL-17-producing Th (Th17) cells have been
      linked to autoimmune diseases such as experimental autoimmune encephalomyelitis
      (EAE), a mouse model of multiple sclerosis (MS). However, what determines Th17
      cell encephalitogenicity is still unresolved. Here, we show that after EAE
      induction, mice deficient for the NF-kappaB regulator MALT1 (Malt1-/- mice)
      exhibit strong lymphocytic infiltration in the CNS, but do not develop any
      clinical signs of EAE. Loss of Malt1 interfered with expression of the Th17
      effector cytokines IL-17 and GM-CSF both in vitro and in vivo. In line with their
      impaired GM-CSF secretion, Malt1-/- Th cells failed to recruit myeloid cells to
      the CNS to sustain neuroinflammation, whereas autoreactive WT Th cells
      successfully induced EAE in Malt1-/- hosts. In contrast, Malt1 deficiency did not
      affect Th1 cells. Despite their significantly decreased secretion of Th17
      effector cytokines, Malt1-/- Th17 cells showed normal expression of lineage
      specific transcription factors. Malt1-/- Th cells failed to cleave RelB, a
      suppressor of canonical NF-kappaB, and exhibited altered cellular localization of
      this protein. Our results indicate that MALT1 is a central, cell-intrinsic factor
      that determines the encephalitogenic potential of inflammatory Th17 cells in
      vivo.

PMID- 23114601
TI  - Improved detection suggests all Merkel cell carcinomas harbor Merkel
      polyomavirus.
AB  - A human polyomavirus was recently discovered in Merkel cell carcinoma (MCC)
      specimens. The Merkel cell polyomavirus (MCPyV) genome undergoes clonal
      integration into the host cell chromosomes of MCC tumors and expresses small T
      antigen and truncated large T antigen. Previous studies have consistently
      reported that MCPyV can be detected in approximately 80% of all MCC tumors. We
      sought to increase the sensitivity of detection of MCPyV in MCC by developing
      antibodies capable of detecting large T antigen by immunohistochemistry. In
      addition, we expanded the repertoire of quantitative PCR primers specific for
      MCPyV to improve the detection of viral DNA in MCC. Here we report that a novel
      monoclonal antibody detected MCPyV large T antigen expression in 56 of 58 (97%)
      unique MCC tumors. PCR analysis specifically detected viral DNA in all 60 unique
      MCC tumors tested. We also detected inactivating point substitution mutations of
      TP53 in the two MCC specimens that lacked large T antigen expression and in only
      1 of 56 tumors positive for large T antigen. These results indicate that MCPyV is
      present in MCC tumors more frequently than previously reported and that mutations
      in TP53 tend to occur in MCC tumors that fail to express MCPyV large T antigen.

PMID- 23114602
TI  - Molecular pathogenesis and clinical management of Fanconi anemia.
AB  - Fanconi anemia (FA) is a rare genetic disorder associated with a high frequency
      of hematological abnormalities and congenital anomalies. Based on multilateral
      efforts from basic scientists and clinicians, significant advances in our
      knowledge of FA have been made in recent years. Here we review the clinical
      features, the diagnostic criteria, and the current and future therapies of FA and
      describe the current understanding of the molecular basis of the disease.

PMID- 23114603
TI  - Lymphangioleiomyomatosis - a wolf in sheep's clothing.
AB  - Lymphangioleiomyomatosis (LAM) is a rare progressive lung disease of women. LAM
      is caused by mutations in the tuberous sclerosis genes, resulting in activation
      of the mTOR complex 1 signaling network. Over the past 11 years, there has been
      remarkable progress in the understanding of LAM and rapid translation of this
      knowledge to an effective therapy. LAM pathogenic mechanisms mirror those of many
      forms of human cancer, including mutation, metabolic reprogramming, inappropriate
      growth and survival, metastasis via blood and lymphatic circulation,
      infiltration/invasion, sex steroid sensitivity, and local and remote tissue
      destruction. However, the smooth muscle cell that metastasizes, infiltrates, and
      destroys the lung in LAM arises from an unknown source and has an innocent
      histological appearance, with little evidence of proliferation. Thus, LAM is as
      an elegant, monogenic model of neoplasia, defying categorization as either benign
      or malignant.

PMID- 23114606
TI  - Advocacy: yes we can.

PMID- 23114604
TI  - Perspectives on whole-organ assembly: moving toward transplantation on demand.
AB  - There is an ever-growing demand for transplantable organs to replace acute and
      chronically damaged tissues. This demand cannot be met by the currently available
      donor organs. Efforts to provide an alternative source have led to the
      development of organ engineering, a discipline that combines cell biology, tissue
      engineering, and cell/organ transplantation. Over the last several years,
      engineered organs have been implanted into rodent recipients and have shown
      modest function. In this article, we summarize the most recent advances in this
      field and provide a perspective on the challenges of translating this promising
      new technology into a proven regenerative therapy.

PMID- 23114607
TI  - Next-generation academic medicine.

PMID- 23114605
TI  - Advances in stem cell therapy for spinal cord injury.
AB  - Spinal cord injury (SCI) is a devastating condition producing great personal and
      societal costs and for which there is no effective treatment. Stem cell
      transplantation is a promising therapeutic strategy, though much preclinical and
      clinical research work remains. Here, we briefly describe SCI epidemiology,
      pathophysiology, and experimental and clinical stem cell strategies. Research in
      stem cell biology and cell reprogramming is rapidly advancing, with the hope of
      moving stem cell therapy closer to helping people with SCI. We examine issues
      important for clinical translation and provide a commentary on recent
      developments, including termination of the first human embryonic stem cell
      transplantation trial in human SCI.

PMID- 23114608
TI  - Introduction of Arthur H. Rubenstein.

PMID- 23114609
TI  - A fortunate life in academic medicine.

PMID- 23114610
TI  - Translating from the rivers of Babylon to the coronary bloodstream.

PMID- 23114612
TI  - Imaging of lysosomal pH changes with a fluorescent sensor containing a novel
      lysosome-locating group.
AB  - Rlyso, a highly selective and sensitive pH sensor, can stain lysosomes with a
      novel lysosome-locating group, methylcarbitol. Rlyso was successfully used to
      detect lysosomal pH changes during apoptosis or induced by chloroquine while
      avoiding the "alkalizing effect" on lysosomes of current lysosomal probes with
      nitrogen-containing sidechains.

PMID- 23114611
TI  - The inhibitory effect of chimeric decoy oligodeoxynucleotide against NF-kappaB
      and Sp1 in renal interstitial fibrosis.
AB  - The pathophysiology of chronic renal disease is characterized by a progressive
      loss of renal function and deposition of the extracellular matrix, leading to
      widespread tissue fibrosis. Much of the matrix in chronic renal disease is
      synthesized by interstitial myofibroblasts, recruited from resident fibroblasts
      and circulating precursors. These changes are believed to be derived from
      epithelial-mesenchymal transition (EMT) of tubuloepithelial cells. To develop a
      novel therapeutic approach for treating renal fibrosis, we examined the
      simultaneous inhibition of the transcription factors NF-kappaB and Sp1 in a mouse
      model of unilateral ureteral obstruction (UUO). To simultaneously inhibit both NF
      kappaB and Sp1, we developed chimeric (Chi) decoy oligodeoxynucleotide (ODN)
      which contained binding sequences for both NF-kappaB and Sp1 in a single decoy
      molecule to enhance the effective use of decoy ODN strategy. Chi decoy ODN
      significantly attenuated tubulointerstitial fibrosis in a mouse model of UUO
      compared to scrambled decoy ODN, as demonstrated by the reduced interstitial
      volume, macrophage infiltration, and fibrosis-related gene expression.
      Interestingly, Chi decoy ODN also regulated EMT-related gene expression, leading
      to the inhibition of renal fibrotic changes in vivo and in vitro. The present
      study demonstrates the feasibility of Chi decoy ODN treatment for preventing
      renal fibrosis and EMT processes. This strategy might be useful to improve the
      clinical outcome after chronic renal disease.

PMID- 23114613
TI  - Formation and inhibition of Nepsilon-(carboxymethyl)lysine in saccharide-lysine
      model systems during microwave heating.
AB  - N(epsilon)-(carboxymethyl) lysine (CML) is the most abundant advanced glycation
      end product (AGE), and frequently selected as an AGEs marker in laboratory
      studies. In this paper, the formation and inhibition of N(epsilon)
      (carboxymethyl)lysine in saccharide-lysine model systems during microwave heating
      have been studied. The microwave heating treatment significantly promoted the
      formation of CML during Maillard reactions, which was related to the reaction
      temperature, time and type of saccharide. The order of CML formation for
      different saccharides was lactose > glucose > sucrose. Then, the inhibition
      effect on CML by five inhibitors was further examined. According to the results,
      ascorbic acid and tocopherol did not affect inhibition of CML, in contrast,
      thiamin, rutin and quercetin inhibited CML formation, and the inhibitory effects
      were concentration dependent.

PMID- 23114614
TI  - Medicinal plants: a source of anti-parasitic secondary metabolites.
AB  - This review summarizes human infections caused by endoparasites, including
      protozoa, nematodes, trematodes, and cestodes, which affect more than 30% of the
      human population, and medicinal plants of potential use in their treatment.
      Because vaccinations do not work in most instances and the parasites have
      sometimes become resistant to the available synthetic therapeutics, it is
      important to search for alternative sources of  anti-parasitic drugs. Plants
      produce a high diversity of secondary metabolites with interesting biological
      activities, such as cytotoxic, anti-parasitic and anti-microbial properties.
      These drugs often interfere with central targets in parasites, such as DNA
      (intercalation, alkylation), membrane integrity, microtubules and neuronal signal
      transduction. Plant extracts and isolated secondary metabolites which can inhibit
      protozoan parasites, such as Plasmodium, Trypanosoma, Leishmania, Trichomonas and
      intestinal worms are discussed. The identified plants and compounds offer a
      chance to develop new drugs against parasitic diseases. Most of them need to be
      tested in more detail, especially in animal models and if successful, in clinical
      trials.

PMID- 23114615
TI  - DNA as a chiral scaffold for asymmetric synthesis.
AB  - The application of DNA-based hybrid catalysts for enantioselective synthesis has
      recently emerged. These catalysts, self-assembled from DNA and a metal complex
      with a specific ligand through supramolecular or covalent anchoring strategies,
      have demonstrated high enantioselectivity in a variety of carbon-carbon or carbon
      heteroatom bond-forming reactions and have expanded their role in asymmetric
      catalysis. In this review, we summarize the advent and significant progress of
      DNA-based asymmetric catalysis and discuss remaining challenges in using DNA as a
      chiral scaffold. We hope that this review will inspire many of today's active
      scientists in asymmetric catalysis.

PMID- 23114616
TI  - Bis-sulfonic acid ionic liquids for the conversion of fructose to 5-hydroxymethyl
      2-furfural.
AB  - Homogenous bis-sulfonic acid ionic liquids (1 mol equiv.) in DMSO  (10 mol
      equiv.) at 100 &#176;C efficiently mediated the conversion of D-fructose into  5
      hydroxymethyl-2-furfural in 75% isolated yield, which was roughly a 10% increment
      compared to the case of the mono-sulfonic acid ionic liquids.

PMID- 23114617
TI  - Antimycobacterial assessment of Salicylanilide benzoates including multidrug
      resistant tuberculosis strains.
AB  - The increasing emergence especially of drug-resistant tuberculosis has  led to a
      strong demand for new anti-tuberculosis drugs. Eighteen salicylanilide benzoates
      were evaluated for their inhibition potential against Mycobacterium tuberculosis,
      Mycobacterium avium and two strains of Mycobacterium kansasii; minimum inhibitory
      concentration values ranged from 0.5 to 16 &#956;mol/L. The most active esters
      underwent additional biological assays. Four benzoates inhibited effectively the
      growth of five multidrug-resistant strains and one extensively drug-resistant
      strain of M. tuberculosis at low concentrations (0.25&#8211;2 &#956;mol/L)
      regardless of the resistance patterns. The highest rate of multidrug-resistant
      mycobacteria inhibition expressed 4-chloro-2-[4-(trifluoromethyl)
      phenylcarbamoyl]phenyl benzoate (0.25&#8211;1 &#956;mol/L). Unfortunately, the
      most potent esters were still considerably cytotoxic, although mostly less than
      their parent salicylanilides.

PMID- 23114618
TI  - Spectroscopic studies on the interaction between EcoRI and CdS QDs and
      conformation of EcoRI in EcoRI-CdS QDs bioconjugates.
AB  - Water-soluble fluorescent quantum dots (QDs) have been widely used in biological
      and biomedical fields, and the interaction between QDs and proteins and the
      conformational structure of the protein in the bioconjugate has attracted
      increasing attention. In this study, UV-Vis spectroscopy, fluorescence quenching,
      CD spectra, gel electrophoresis and Fourier transform infrared (FTIR)
      spectroscopic techniques were used to systematically investigate the interaction
      between type II restriction endonuclease (EcoRI) and CdS QDs and the
      conformational structure of EcoRI in the EcoRI-CdS QDs bioconjugates. The results
      indicated that electrostatic interactions played a major role in the binding
      reaction at pH 6.0, and the nature of quenching was static, resulting in forming
      CdS QDs-EcoRI bioconjugates. FTIR and CD spectra studies indicated a decrease of
      alpha-helical and turn structures accompanied by the increase of beta-sheet
      structures of EcoRI in the bioconjugates. This study showed that the interaction
      between EcoRI and CdS QDs resulted in a change in the secondary structure of
      EcoRI after it was conjugated with CdS QDs, but the enzyme activity was
      maintained.

PMID- 23114619
TI  - A poor imitation of a natural process: a call to reconsider the iPSC engineering
      technique.
AB  - Reprogramming somatic cells into a pluripotent state is expected to initiate a
      new era in medicine. Because the precise underlying mechanism of reprogramming
      remains unclear, many efforts have been made to optimize induced pluripotent stem
      cell (iPSC) engineering. However, satisfactory results have not yet been
      attained. In this review, we focus on recent roadblocks in iPSC reprogramming
      engineering, such as the inefficiency of the process, tumorigenicity and
      heterogeneity of the generation. We conclude that cell reprogramming is a
      naturally occurring phenomenon rather than a biological technique. We will only
      be able to mimic the natural process of reprogramming when we fully understand
      its underlying mechanism. Finally, we highlight the alternative method of direct
      conversion, which avoids the use of iPSCs to generate cell materials for patient
      specific cell therapy.

PMID- 23114620
TI  - Choline-releasing glycerophosphodiesterase EDI3 links the tumor metabolome to
      signaling network activities.
AB  - Recently, EDI3 was identified as a key factor for choline metabolism that
      controls tumor cell migration and is associated with metastasis in endometrial
      carcinomas. EDI3 cleaves glycerophosphocholine (GPC) to form choline and glycerol
      3-phosphate (G3P). Choline is then further metabolized to phosphatidylcholine
      (PtdC), the major lipid in membranes and a key player in membrane-mediated cell
      signaling. The second product, G3P, is a precursor molecule for several lipids
      with central roles in signaling, for example lysophosphatidic acid (LPA),
      phosphatidic acid (PA) and diacylglycerol (DAG). LPA activates intracellular
      signaling pathways by binding to specific LPA receptors, including membrane-bound
      G protein-coupled receptors and the intracellular nuclear receptor, PPARgamma.
      Conversely, PA and DAG mediate signaling by acting as lipid anchors that bind and
      activate several signaling proteins. For example, binding of GTPases and PKC to
      PA and DAG, respectively, increases the activation of signaling networks,
      mediating processes such as migration, adhesion, proliferation or anti-apoptosis
      all relevant for tumor development. We present a concept by which EDI3 either
      directly generates signaling molecules or provides "membrane anchors" for
      downstream signaling factors. As a result, EDI3 links choline metabolism to
      signaling activities resulting in a more malignant phenotype.

PMID- 23114622
TI  - Effect of lexical proficiency on reading strategies used for shallow and deep
      orthographies.
AB  - The aim of the present study was to explore how different levels of proficiency
      in deep orthography (DO) influence the reading strategies used for sentences
      containing both shallow orthographies and DO, and to examine the neural
      correlates involved. High-proficiency participants, who depend on rapid and
      direct semantic retrieval by the lexical route, activated the anterior cingulate
      cortex, middle frontal, and fusiform gyri. Low-proficiency participants, who rely
      on the sublexical route, activated inferior parietal lobule and inferior frontal
      gyrus. These findings suggest that level of proficiency in DO modulates the
      selection of specific reading strategies, and that the neural pathways underlying
      these strategies are separately laid out in the cortical areas.

PMID- 23114621
TI  - The mysterious human epidermal cell cycle, or an oncogene-induced differentiation
      checkpoint.
AB  - Fifteen years ago, we reported that proto-oncogene MYC promoted differentiation
      of human epidermal stem cells, a finding that was surprising to the MYC and the
      skin research communities. MYC was one of the first human oncogenes identified,
      and it had been strongly associated with proliferation. However, it was later
      shown that MYC could induce apoptosis under low survival conditions. Currently,
      the notion that MYC promotes epidermal differentiation is widely accepted, but
      the cell cycle mechanisms that elicit this function remain unresolved. We have
      recently reported that keratinocytes respond to cell cycle deregulation and DNA
      damage by triggering terminal differentiation. This mechanism might constitute a
      homeostatic protection face to cell cycle insults. Here, I discuss recent and not
      so-recent evidence suggesting the existence of a largely unexplored oncogene
      induced differentiation response (OID) analogous to oncogene-induced apoptosis
      (OIA) or senescence (OIS). In addition, I propose a model for the role of the
      cell cycle in skin homeostasis maintenance and for the dual role of MYC in
      differentiation.

PMID- 23114623
TI  - Resveratrol attenuates L-DOPA-induced hydrogen peroxide toxicity in neuronal
      cells.
AB  - A variety of polyphenol antioxidant compounds derived from natural products have
      demonstrated neuroprotective activity against neuronal cell death. The objective
      of this study was to investigate the effect of resveratrol (RESV) and
      bioflavonoids in attenuating hydrogen peroxide (H(2)O(2))-induced oxidative
      stress in neuronal cells. H2O2 levels were increased by the addition of L-3,4
      dihydroxyphenylalanine (L-DOPA) to cultured dopaminergic SKNSH cells. H(2)O(2)
      was monitored by peroxyfluor-1, a selective H(2)O(2) optical probe. To examine
      the neuroprotective effects of RESV and bioflavonoids against L-DOPA, we
      cotreated RESV, quercetin, or (-) epigallocatechin gallate with L-DOPA and
      monitored for H(2)O(2) levels. The combination of RESV and L-DOPA was 50% more
      effective at reducing H(2)O(2) levels than the combination of quercetin or
      epigallocatechin gallate with L-DOPA. However, the combination of each
      antioxidant with L-DOPA was effective at preserving cell viability.

PMID- 23114624
TI  - Oligo-nuclear silver thiocyanate complexes with monodentate tertiary phosphine
      ligands, including novel 'cubane' and 'step' tetramer forms of AgSCN : PR3
      (1:1)4.
AB  - Adducts of a number of tertiary pnicogen ligands ER(3) (triphenyl-phosphine and 
      arsine (PPh(3),AsPh(3)), diphenyl,2-pyridylphosphine (PPh(2)py), tris(4
      fluorophenyl)phosphine (P(C(6)H(4)-4F)(3)), tris(2-tolyl)phosphine (P(o-tol)(3)),
      tris(cyclohexyl)phosphine (PCy(3))), with silver(I) thiocyanate, AgSCN are
      structurally and spectroscopically characterized. The 1:3 AgSCN : ER(3) complexes
      structurally defined (for PPh(3),AsPh(3) (diversely solvated)) take the form
      [(R(3)E)(3)AgX], the thiocyanate X = NCS being N-bound, thus [(Ph(3)E)Ag(NCS)]. A
      1:2 complex with PPh(2)py, takes the binuclear form
      [(pyPh(2)P)(2)Ag()Ag(PPh(2)py)(2)] with an eight-membered cyclic core. 1:1
      complexes are defined with PPh(2)py, P(o-tol)(3) and PCy(3); binuclear forms
      [(R(3)P)Ag()Ag(PR(3))] are obtained with P(o-tol)(3) (two polymorphs), while
      novel isomeric tetranuclear forms, which may be envisaged as dimers of dimers,
      are obtained with PPh(2)py, and, as further polymorphs, with PCy(3); these latter
      may be considered as extensions of the 'cubane' and 'step' forms previously
      described for [(R(3)E)AgX](4) (X = halide) complexes. Solvent-assisted
      mechanochemical or solvent-assisted solid-state synthesis methods were employed
      in some cases, where complexes could not be obtained by conventional solution
      methods, or where such methods yielded a mixture of polymorphs unsuitable for
      solid-state spectroscopy. The wavenumbers of the nu(CN) bands in the IR spectra
      are in broad agreement with the empirical rule that distinguishes bridging from
      terminal bonding, but exceptions occur for compounds that have a double SCN
      bridged dimeric structure, and replacement of PPh(3) with PPh(2)py apparently
      causes a significant decrease in nu(CN) to well below the range expected for
      bridging SCN in these structures. (31)P CP MAS NMR spectra yield additional
      parameters that allow a correlation between the structures and spectra.

PMID- 23114625
TI  - In-vivo investigation of laser-induced choroidal neovascularization in rat using
      spectral-domain optical coherence tomography (SD-OCT).
AB  - PURPOSE: This study investigated the in-vivo formation process of laser-induced
      choroidal neovascularization (CNV) in rat using high-resolution spectral-domain
      optical coherence tomography (SD-OCT), and compared the results to histological
      methods. METHODS: Brown Norway rats (n = 60, 6-8 weeks of age) received 532-nm
      diode laser photocoagulation. SD-OCT and fluorescein angiography (FA) were
      performed in vivo 2, 5, 7, 14, and 21 days post-laser application. Haematoxylin
      and eosin (H&E) staining and immunohistochemistry for CD31, phosphorylated
      vascular endothelial factor receptor 2 (pVEGFR2) were conducted at each time
      point to observe the CNV in vitro. Choroidal flatmount preparations were observed
      using a confocal laser scanning microscope (CLSM) and a scanning electron
      microscope (SEM). RESULTS: SD-OCT monitored the longitudinal morphological
      changes of laser-induced CNV. CNV reached its maximal size on day 7, and began a
      gradual reduction on day 14. FA revealed similar dynamic changes in leakage. CNV
      thickness, as assessed by SD-OCT, was consistent with H&E-stained sections at
      each time point. CLSM and SEM revealed the details of the fibrovascular membrane.
      CD31 and pVEGFR2 expression supported the results of SD-OCT and histology.
      CONCLUSIONS: SD-OCT was a convenient and reliable tool for the imaging of the CNV
      formation process and quantification of the lesion size in vivo.

PMID- 23114626
TI  - West Nile virus NS2A protein facilitates virus-induced apoptosis independently of
      interferon response.
AB  - The flavivirus NS2A protein is a small, multifunctional protein, involved in
      replication, virion formation and regulation of the innate immune response. Using
      the Kunjin strain of West Nile virus (WNV(KUN)) we previously demonstrated that a
      single amino acid change from alanine to proline at position 30 of the NS2A
      protein (A30P) reduced viral cytopathicity in cells and virulence in mice. To
      further investigate functions of the NS2A protein we have substituted alanine at
      position 30 with different amino acids (A30 mutants) in a WNV(KUN) infectious
      clone. The virulence of mutant viruses in wild-type (WT) and IRF3/IRF7 double
      knockout mice was influenced by the amino acid change and ranged from high to low
      in the order of WT>A30L>A30E>A30P/A30G. Moreover, infection of beta interferon
      (IFN-beta)-deficient Vero cells with A30P virus showed less pronounced
      chromosomal DNA degradation and lower percentage of cells with positive TUNEL
      labelling than in WT virus infection, indicating a role for the WT NS2A protein
      in IFN-independent apoptotic cell death.

PMID- 23114627
TI  - Addition of a single N-glycan to street rabies virus glycoprotein enhances virus
      production.
AB  - Most street rabies virus G proteins have two N-glycosylation sites, i.e. Asn(37)
      and Asn(319), whereas additional sites are found in fixed (laboratory adapted)
      viruses. In this study, we performed a pseudotyped virus assay using G-deficient
      rabies virus and demonstrated that single-N-glycan additions to the G protein of
      street rabies virus strain 1088, which are found in adapted strains, enhanced
      virus production in neural and non-neural cell lines, while additions to Asn(194)
      or Asn(247) enhanced production greatly. Moreover, we found that N-glycan
      additions at Asn(194) or Asn(247) facilitated the production of cell-associated
      virus. In contrast, deletion of the sequon at Asn(37) reduced viral production,
      while a deletion at Asn(319) resulted in extensive loss of production.
      Furthermore, G proteins lacking an N-glycan at Asn(319) failed to fold into their
      correct structure and lost their fusion activity, indicating that Asn(319) N
      glycosylation is important for the functional expression of street virus G
      proteins.

PMID- 23114629
TI  - Antigenic diversity and seroprevalences of Torque teno viruses in children and
      adults by ORF2-based immunoassays.
AB  - Torque teno viruses (TTVs) circulate widely among humans, causing persistent
      viraemia in healthy individuals. Numerous TTV isolates with high genetic
      variability have been identified and segregated into 29 species of five major
      phylogenetic groups. To date, the diversity of TTV sequences, challenges in
      protein expression and the subsequent lack of serological assays have hampered
      TTV seroprevalence studies. Moreover, the antigenic relationships of different
      TTVs and their specific seroprevalences in humans remain unknown. For five TTV
      strains--belonging to different species of four genogroups--we developed, using
      recombinant glutathione S-transferase (GST)-fused TTV ORF2 proteins, glutathione
      GST capture enzyme immunoassays (EIAs) detecting antibodies towards
      conformational epitopes. We then analysed serum samples from 178 healthy adults
      and 108 children; IgG reactivities were observed either towards a single strain
      or towards multiple strains, which pointed to antigenic distinction of TTV
      species. The overall seroprevalence for the five TTVs peaked at 43 % (18 of 42)
      in children 2-4 years of age, subsequently declined, and again reached 42 % (74
      of 178) among adults. TTV6 species-specific IgG predominated in children, whereas
      that for TTV13 predominated in adults. During a 3 year follow-up of the same
      children, both species-specific seroconversions and seroreversions occurred. This
      is the first EIA-based study of different TTVs, providing a new approach for
      seroepidemiology and diagnosis of TTV infections. Our data suggest that different
      TTVs in humans may differ in antiviral antibody profiles, infection patterns and
      epidemiology.

PMID- 23114628
TI  - p53 controls hepatitis C virus non-structural protein 5A-mediated downregulation
      of GADD45alpha expression via the NF-kappaB and PI3K-Akt pathways.
AB  - Growth arrest and DNA-damage-inducible gene 45-alpha (GADD45alpha) protein has
      been shown to be a tumour suppressor and is implicated in cell-cycle arrest and
      suppression of cell growth. The hepatitis C virus (HCV) non-structural 5A (NS5A)
      protein plays an important role in cell survival and is linked to the development
      of hepatocellular carcinoma (HCC). However, the role of HCV NS5A in the
      development of HCC remains to be clarified. This study sought to determine
      whether GADD45alpha mediates HCV NS5A-induced cellular survival and to elucidate
      the molecular mechanism of GADD45alpha expression regulated by HCV NS5A. It was
      found that HCV NS5A downregulated GADD45alpha expression at the transcriptional
      level by decreasing promoter activity, mRNA transcription and protein levels.
      Knockdown of p53 resulted in a similar decrease in GADD45alpha expression to that
      caused by HCV NS5A, whilst overexpression of p53 reversed the HCV NS5A-mediated
      downregulation of GADD45alpha. HCV NS5A repressed p53 expression, which was
      followed by a subsequent decrease in GADD45alpha expression. Further evidence was
      provided showing that HCV NS5A led to increases of phosphorylated nuclear factor
      kappaB and Akt levels. Inhibition of these pathways using pharmacological
      inhibitors or specific small interfering RNAs rescued HCV NS5A-mediated
      downregulation of p53 and GADD45alpha. It was also found that HCV NS5A protein
      and depletion of GADD45alpha increased cell growth, whereas ectopic expression of
      GADD45alpha eliminated HCV NS5A-induced cell proliferation. These results
      indicated that HCV NS5A downregulates GADD45alpha expression and subsequently
      triggers cellular proliferation. These findings provide new insights suggesting
      that HCV NS5A could contribute to the occurrence of HCV-related HCC.

PMID- 23114630
TI  - Street rabies virus causes dendritic injury and F-actin depolymerization in the
      hippocampus.
AB  - Rabies is an acute viral infection of the central nervous system and is typically
      fatal in humans and animals; however, its pathogenesis remains poorly understood.
      In this study, the morphological changes of dendrites and dendritic spines in the
      CA1 region of the hippocampus were investigated in mice that were infected
      intracerebrally with an MRV strain of the street rabies virus. Haematoxylin and
      eosin and fluorescence staining analysis of brain sections from the infected mice
      showed very few morphological changes in the neuronal bodies and neuronal
      processes. However, we found a significant decrease in the number of dendritic
      spines. Primary neuronal cultures derived from the hippocampus of mice (embryonic
      day 16.5) that were infected with the virus also showed an obvious decrease in
      the number of dendritic spines. Furthermore, the decrease in the number of
      dendritic spines was related to the depolymerization of actin filaments (F
      actin). We propose that the observed structural changes can partially explain the
      severe clinical disease that was found in experimental models of street rabies
      virus infections.

PMID- 23114631
TI  - What was your fracture risk evaluated by FRAX(r) the day before your osteoporotic
      fracture?
AB  - Osteoporotic fracture (OF) is one of the major causes of morbidity and mortality
      in industrialized countries. Switzerland is among the countries with the greatest
      risk. Our aim was (1) to calculate the FRAX((r)) in a selected Swiss population
      the day before the occurrence of an OF and (2) to compare the results with the
      proposed Swiss FRAX((r)) thresholds. The Swiss Association Against Osteoporosis
      proposed guidelines for the treatment of osteoporosis based on age-dependent
      thresholds. To identify a population at a very high risk of osteoporotic
      fracture, we included all consecutive patients in the active OF pathway cohort
      from the Lausanne University Hospital, Switzerland. FRAX((r)) was calculated with
      the available data the day before the actual OF. People with a FRAX((r)) body
      mass index (BMI) or a FRAX((r)) (bone mineral density) BMD lower than the Swiss
      thresholds were not considered at high risk. Two-hundred thirty-seven patients
      were included with a mean age of 77.2 years, and 80 % were female. Major types of
      fracture included hip (58 %) and proximal humerus (25 %) fractures. Mean
      FRAX((r)) BMI values were 28.0, 10.0, 13.0, 26.0, and 37.0 % for age groups 50
      59, 60-69, 70-79, and 80-89 years old, respectively. Fifty percent of the
      population was not considered at high risk by the FRAX((r)) BMI. FRAX((r)) BMD
      was available for 95 patients, and 45 % had a T score < -2.5 standard deviation.
      Only 30 % of patients with a normal or osteopenic BMD were classified at high
      risk by FRAX((r)) BMD. The current proposed Swiss thresholds were not able to
      classify at high risk in 50 to 70 % of the studied population the day before a
      major OF.

PMID- 23114632
TI  - The experience and impact of gout in Maori and Pacific people: a prospective
      observational study.
AB  - Although high prevalence of gout in Maori and Pacific people is well-documented,
      the experience of disease in these groups has not been explored in detail. The
      aim of this analysis was to describe the experience and impact of gout in Maori
      and Pacific people. Patients with gout for <10 years were recruited from primary
      and secondary care settings into a prospective observational study (n = 291; 37
      Maori, 35 Pacific, and 219 not Maori or Pacific). Participants attended a
      baseline study visit which included a comprehensive clinical assessment. Serum
      urate, flare frequency and activity limitation were recorded at baseline and
      after 1 year. Maori and Pacific participants had earlier age of onset (by 9
      years), higher flare frequency and more features of joint inflammation. Serum
      urate concentrations were higher in the Maori and Pacific patients at baseline,
      despite greater use of allopurinol. Maori and Pacific patients reported greater
      pain and activity limitation and lower health-related quality of life. The cost
      of gout treatment was more than three times higher in the Maori and Pacific
      patients. After 1 year, the higher flare frequency and activity limitation
      persisted in the Maori and Pacific patients. Maori and Pacific people with gout
      experience early onset, severe disease with frequent flares and poorly controlled
      hyperuricaemia. Maori and Pacific ethnicity should be recognised as a prognostic
      factor for more severe outcomes in this disease, and intensive efforts should be
      made to work with these patients to control serum urate and prevent flares.

PMID- 23114634
TI  - Lymphobronchial fistula: another complication associated with lymphobronchial
      tuberculosis in children.

PMID- 23114633
TI  - Quality improvement guidelines for pediatric abscess and fluid drainage.

PMID- 23114635
TI  - In vitro studies of calcium phosphate silicate bone cements.
AB  - A novel calcium phosphate silicate bone cement (CPSC) was synthesized in a
      process, in which nanocomposite forms in situ between calcium silicate hydrate (C
      S-H) gel and hydroxyapatite (HAP). The cement powder consists of tricalcium
      silicate (C(3)S) and calcium phosphate monobasic (CPM). During cement setting,
      C(3)S hydrates to produce C-S-H and calcium hydroxide (CH); CPM reacts with the
      CH to precipitate HAP in situ within C-S-H. This process, largely removing CH
      from the set cement, enhances its biocompatibility and bioactivity. The testing
      results of cell culture confirmed that the biocompatibility of CPSC was improved
      as compared to pure C(3)S. The results of XRD and SEM characterizations showed
      that CPSC paste induced formation of HAP layer after immersion in simulated body
      fluid for 7 days, suggesting that CPSC was bioactive in vitro. CPSC cement, which
      has good biocompatibility and low/no cytotoxicity, could be a promising candidate
      as biomedical cement.

PMID- 23114636
TI  - The influence of phosphorus precursors on the synthesis and bioactivity of SiO2
      CaO-P 2O 5 sol-gel glasses and glass-ceramics.
AB  - Bioactive glasses and glass-ceramics of the SiO(2)-CaO-P(2)O(5) system were
      synthesised by means of a sol-gel method using different phosphorus precursors
      according to their respective rates of hydrolysis-triethylphosphate
      (OP(OC(2)H(5))(3)), phosphoric acid (H(3)PO(4)) and a solution prepared by
      dissolving phosphorus oxide (P(2)O(5)) in ethanol. The resulting materials were
      characterised by differential scanning calorimetry and thermogravimetry, X-ray
      diffraction, Fourier transform infrared spectroscopy, scanning electron
      microscopy coupled with energy dispersive X-ray spectroscopy and by in vitro
      bioactivity tests in acellular simulated body fluid. The different precursors
      significantly affected the main steps of the synthesis, beginning with the time
      required for gel formation. The most striking influence of these precursors was
      observed during the thermal treatments at 700-1,200  degrees C that were used to
      convert the gels into glasses and glass-ceramics. The samples exhibited very
      different mineralisation behaviours; especially those prepared using the
      phosphoric acid, which had a reduced onset temperature of crystallisation and an
      increased resistance to devitrification. However, all resulting materials were
      bioactive. The in vitro bioactivity of these materials was strongly affected by
      the heat treatment temperature. In general, their bioactivity decreased with
      increasing treatment temperature. For crystallised samples obtained above 900 
      degrees C, the bioactivity was favoured by the presence of two crystalline
      phases: wollastonite (CaSiO(3)) and tricalcium phosphate (alpha-Ca(3)(PO(4))(2)).

PMID- 23114637
TI  - New insights into the variability of reproduction modes in European populations
      of Rubus subgen. Rubus: how sexual are polyploid brambles?
AB  - Rubus subgen. Rubus includes common European species with highly complicated
      taxonomy, ongoing hybridisation and facultative apomixis. Out of approximately
      750 species recognised in Europe, only 3 diploid sexual species are known, along
      with numerous apomictic brambles that are highly connected to polyploidy. One
      exception of a tetraploid taxon is R. ser. Glandulosi, which is known for
      prevalent sexuality. This taxon highly hybridises with tetraploid members of R.
      ser. Discolores and leads to the origin of many hybridogenous populations and
      individuals. In this study, we verify reproduction modes in different diploid,
      triploid and tetraploid species of subgen. Rubus, with focus on taxa putatively
      involved in such hybridisation by applying flow cytometric seed screen analysis.
      We found 100 % sexuality of diploid species, whereas triploid species had
      obligate unreduced embryo sac development. In contrast, tetraploid plants had
      varying degrees of sexuality. Additionally, we discovered that R. bifrons has the
      ability to undergo a reproduction mode switch as a reaction to environmental
      conditions. These results provide insight into reproductive modes of European
      brambles and shed light on their reticulate evolution and speciation.

PMID- 23114638
TI  - Mechanism of seedlessness in a new lemon cultivar 'Xiangshui' [Citrus limon (L.)
      Burm. F].
AB  - Seedlessness is an important economic trait of lemon. Understanding the cellular
      and molecular mechanisms of seedlessness in 'Xiangshui' lemon requires detailed
      data on pollen and embryo sac fertility, embryo development and compatibility
      mechanisms governing self- and cross-pollination. The results of the current
      study indicate that the fertility of pollen and mature embryo sac remains normal.
      When flowers were self- or cross-pollinated, pollen grains of 'Xiangshui' were
      able to germinate on the stigma. In the case of self-pollination, pollen tubes
      became twisted, tube tips enlarged and tubes ruptured in the bottom of stigma.
      Following cross-pollination, tubes were able to grow normally in the style and
      ovary and enter the embryo sac, where double fertilization took place. Embryonic
      development resulting from cross-pollination was normal. After cross-pollination,
      the zygote began to divide at 2 weeks post-pollination, with early globular
      embryos observed after 3 weeks, globular and heart-shaped embryos at 4 weeks,
      torpedo-shaped embryos at 5 weeks, cotyledonary embryos at 6 weeks and thereafter
      germinable seeds. After self-pollination, however, ovules began to abort at 2
      weeks post-pollination, with ovules disappearing at 5 weeks, ultimately producing
      seedless fruits. Emasculated unpollinated flowers also developed into seedless
      fruits, indicating that seedlessness contributes to parthenocarpy. However,
      gametophytic self-incompatibility has a major role in seedlessness in 'Xiangshui'
      lemon by blocking fertilization at the bottom of the stigma.

PMID- 23114639
TI  - Syntheses and photophysical properties of 5'-6-locked fluorescent nucleosides.
AB  - Nine fluorescent 5'-6-locked nucleosides were synthesized by condensation of
      various 1,2-diketones with 5-amino-2'-deoxycytidine. The nucleosides have
      different substituents on the pyrazine core structure, ranging from two methyl
      groups to polyaromatic rings. The photophysical properties of each nucleoside
      were determined, with the nucleosides displaying diverse absorption and emission
      maxima, extinction coefficients and quantum yields. The nucleoside with the
      highest fluorescence brightness was phosphitylated and incorporated into an
      oligonucleotide by means of automated oligonucleotide synthesis. The labelled
      oligonucleotide in aqueous buffer exhibited a substantially lowered extinction
      coefficient and quantum yield compared to the nucleoside in THF. The
      photophysical properties of the nucleoside were also compared in different DNA
      structural contexts, a single strand, a 14-mer duplex, a 14-mer duplex with an 11
      mer overhang, and a 25-mer nicked duplex labelled at the nick site. Circular
      dichroism and melting temperature studies verified that the nucleoside did not
      perturb or destabilize the DNA helixes. In fact, when incorporated at the nick
      site, the nucleoside was found to stabilize the nicked duplex notably compared to
      its unmodified counterpart. The brightness of the fluorescent nucleoside in DNA
      increased as the polarity of its surroundings decreased, being highest in the 25
      mer nicked duplex where exposure to the polar solvent is minimized by stacking to
      the adjacent bases on both the 3'- and 5'-side. The nucleosides brightness in the
      nicked duplex was also found to increase with lowered temperature, in accordance
      with expected temperature-dependent changes in the stacked-unstacked equilibrium
      at the nick site.

PMID- 23114640
TI  - Use of metformin for women with polycystic ovary syndrome.

PMID- 23114641
TI  - Porfimer-sodium (Photofrin-II) in combination with ionizing radiation inhibits
      tumor-initiating cell proliferation and improves glioblastoma treatment efficacy.
AB  - Tumor relapse and tumor cell repopulation has been explained partially by the
      drug-free break period between successive conventional treatments. Strategies to
      overcome tumor relapse have been proposed, such as the use of chemotherapeutic
      drugs or radiation in small, frequent fractionated doses without an extended
      break period between treatment intervals. Yet, tumors usually acquire resistance
      and eventually escape the therapy. Several mechanisms have been proposed to
      explain the resistance of tumors to therapy, one of which involves the cancer
      stem cell or tumor-initiating cell (TIC) concept. TICs are believed to resist
      many conventional therapies, in part due to their slow proliferation and self
      renewal capacities. Therefore, emerging efforts to eradicate TICs are being
      undertaken. Here we show that treatment with Photofrin II, among the most
      frequently used photosensitizers, sensitized a TIC-enriched U-87MG human
      glioblastoma cell to radiation, and improve treatment outcome when used in
      combination with radiotherapy. A U-87MG tumor cell population enriched with
      radiation-resistant TICs becomes radio-sensitive, and an inhibition of cell
      proliferation and an increase in apoptosis are found in the presence of Photofrin
      II. Furthermore, U-87MG tumors implanted in mice treated with Photofrin II and
      radiation exhibit a significant reduction in angiogenesis and vasculogenesis, and
      an increased percentage of apoptotic TICs when compared with tumors grown in mice
      treated with radiation alone. Collectively, our results offer a new possible
      explanation for the therapeutic effects of radiosensitizing agents, and suggest
      that combinatorial treatment modalities can effectively prolong treatment outcome
      of glioblastoma tumors by inhibiting tumor growth mediated by TICs.

PMID- 23114642
TI  - The emerging anti-proliferative role of Nutlin-3 in the pathogenesis of systemic
      malignancies.

PMID- 23114643
TI  - Small molecule kinase inhibitors block the ZAK-dependent inflammatory effects of
      doxorubicin.
AB  - The adverse side effects of doxorubicin, including cardiotoxicity and cancer
      treatment-related fatigue, have been associated with inflammatory cytokines, many
      of which are regulated by mitogen-activated protein kinases (MAPKs). ZAK is an
      upstream kinase of the MAPK cascade. Using mouse primary macrophages cultured
      from ZAK-deficient mice, we demonstrated that ZAK is required for the activation
      of JNK and p38 MAPK by doxorubicin. Nilotinib, ponatinib and sorafenib strongly
      suppressed doxorubicin-mediated phosphorylation of JNK and p38 MAPK. In addition,
      these small molecule kinase inhibitors blocked the expression of IL-1beta, IL-6
      and CXCL1 RNA and the production of these proteins. Co-administration of
      nilotinib and doxorubicin to mice decreased the expression of IL-1beta RNA in the
      liver and suppressed the level of IL-6 protein in the serum compared with mice
      that were injected with doxorubicin alone. Therefore, by reducing the production
      of inflammatory mediators, the inhibitors identified in the current study may be
      useful in minimizing the side effects of doxorubicin and potentially other
      chemotherapeutic drugs.

PMID- 23114644
TI  - Overexpression of cyclin B1 antagonizes chemotherapeutic-induced apoptosis
      through PTEN/Akt pathway in human esophageal squamous cell carcinoma cells.
AB  - The role of cyclin B1 in the clinical therapeutic sensitivity of human esophageal
      squamous cell carcinoma (ESCC) remains to be defined. In this study, we found
      that elevated cyclin B1 expression attenuated the apoptosis induced by cisplatin
      or paclitaxel, while knockdown of cyclin B1 enhanced cisplatin or paclitaxel
      sensitivity in ESCC cells. Cyclin B1-mediated apoptosis may rely on the Bcl-2
      dependent mitochondria-regulated intrinsic death pathway, and the antagonizing
      effect of cyclin B1 on chemotherapeutic agent-induced apoptosis was through
      PTEN/Akt pathway. Therefore, cyclin B1 might be a therapeutic target for the
      development of specific and efficient approaches in the treatment of ESCC.

PMID- 23114645
TI  - Clinical usefulness of human epidermal growth factor receptor-2 extracellular
      domain as a biomarker for monitoring cancer status and predicting the therapeutic
      efficacy in breast cancer.
AB  - We assessed the clinical usefulness of human epidermal growth factor receptor-2
      extracellular domain (HER2ECD) as a biomarker for detecting cancer and monitoring
      disease status and for predicting the efficacy of anticancer treatment in breast
      cancer. Five-hundred and eighty serum samples from 252 patients with breast
      cancer were examined for the concentration of HER2ECD to compare with
      conventional tumor markers (CEA, CA15-3, NCC-ST439 and BCA225). Also, in 19
      patients with HER2-overexpressed advanced or recurrent breast cancer who were
      treated with trastuzumab, clinical outcomes were evaluated retrospectively to
      determine whether their serum HER2ECD levels predict clinical responses. The
      proportion of patients with elevated HER2ECD levels was 15.1%, which was
      compatible with those with elevated conventional marker levels. In patients with
      HER2-overexpressed breast cancer, the positive rate of HER2ECD was significantly
      higher (24.1%) than those of conventional markers (7.4-12.9%), suggesting the
      usefulness of HER2ECD for detecting cancer in this population. HER2-overexpressed
      patients responding to trastuzumab (12 of 19 patients) showed significantly
      higher serum HER2ECD level (p = 0.033) and longer time to progression (TTP) (p =
      0.039) and overall survival (OS) (p = 0.031) than did patients not responding
      (seven patients). Furthermore, higher response rates were observed in patients
      with elevated HER2ECD levels than in patients without elevated HER2ECD levels
      (91.3% vs. 14.3%, p = 0.032), whereas there was no difference in survival between
      the two groups. The results suggest that HER2ECD is a useful biomarker not only
      for detecting breast cancer recurrence but also for predicting tumor responses to
      trastuzumab.

PMID- 23114646
TI  - Prognostic impact of EMT (epithelial-mesenchymal-transition)-related protein
      expression in endometrial cancer.
AB  - OBJECTIVES: The epithelial-mesenchymal-transition (EMT) is an important step in
      the invasion and metastasis of cancer. A critical molecular feature of this
      process is the downregulation of E-cadherin expression, which is mainly
      controlled by Snail-related zinc-finger transcription factors (Snail and Slug).
      The aim of this study was to evaluate the prognostic impact of EMT-related
      protein (E-cadherin, Snail and Slug) expression in endometrial cancer. METHODS:
      An immunohistochemical analysis was conducted using tissue microarray samples of
      354 primary tumors and 30 metastases of endometrial carcinomas, and the
      relationship between protein expression, clinicopathological features and
      outcomes were investigated. RESULTS: Reduced E-cadherin was seen in 39.8% of
      primary tumors. Reduced E-cadherin was seen in 19.5%, 40.8% and 72.7% of G1, G2
      and G3 endometrioid adenocarcinomas, respectively. The nuclear expression of
      Snail and Slug were positive in 16.9% and 3.7% of primary tumors, respectively.
      EMT status, which was represented by both reduced E-cadherin and nuclear
      expression of Snail, was significantly associated with histological type, FIGO
      stage, myometrial invasion, positive peritoneal cytology and patient survival (p
      < 0.01). There was no difference in the rates of EMT status between the primary
      tumors and metastases. A multivariate analysis showed that EMT-positive status
      was a significant predictor for both the progression-free survival and overall
      survival (p < 0.01). CONCLUSIONS: These data indicate that EMT status has a
      prognostic impact in endometrial cancer. Therefore, the clarification and control
      of EMT signaling is a promising molecular targeting therapy in endometrial
      cancer.

PMID- 23114647
TI  - A bilateral primary yolk sac tumor of the lung associated with chromosome 3
      polysomy: understanding the Oct 3/4 and Sox 2 interaction.
AB  - Extragonadal germ cell tumors (EGCTs) in the lung are extremely rare and their
      pathogenesis is poorly understood. We report a case in a 48-year-old female which
      was very aggressive and stained positive for primoridial germ cell markers.
      Interestingly, there was chromosome 3 polysomy noted. To our knowledge this is
      the first chromosomal aberration noted in a primary germ cell tumor of the lung.

PMID- 23114648
TI  - Toward personalized therapy for chronic lymphocytic leukemia: DSC and cDNA
      microarray assessment of two cases.
AB  - The differences in clinical course of chronic lymphocytic leukemia could have an
      impact on variations in a patient's response to therapy. Our published results
      revealed that thermal transition (95 +/- 5 degrees C) in differential scanning
      calorimetry profiles appear to be characteristic for the advanced stage of CLL.
      Moreover, a decrease/loss of this transition in nuclei from leukemic cells
      exposed to drugs ex vivo could indicate their diverse efficacy. It seems that the
      lack of changes in thermal profile could predict patient's drug resistance. In
      this study, we demonstrate the results obtained after drug treatment of leukemic
      cells by calorimetry, apoptosis-related parameters involved in expression of
      genes using cDNA microarray and western blot. These data were compared with the
      patients' clinical parameters before and after RCC therapy (rituximab +
      cladribine + cyclophosphamide). The complementary analysis of studied cases with
      opposite clinical response (CR or NR) revealed a strong relationship between
      clinical data, differences in thermal scans and apoptosis-related gene
      expression. We quantified expression of eight of apoptosis-related 89 genes,
      i.e., NOXA, PUMA, APAF1, ESRRBL1, CASP3, BCL2, BCL2A1 and MCL1. Particular
      differences in NOXA and BCL2 expression were revealed. NOXA expression in cells
      of patients who achieved a complete response to RCC therapy was 0.44 times higher
      in comparison to control ones. Interestingly, in the case of patients who did not
      respond to immunotherapy, NOXA expression was highly downregulated (RQ = 4.39) as
      compared with untreated cells. These results were confirmed by distinct cell
      viability, protein expression as well as by differences in calorimetry profiles.

PMID- 23114649
TI  - Adaptation of a chemosensitivity assay to accurately assess pemetrexed in ex vivo
      cultures of lung cancer.
AB  - PURPOSE: Pemetrexed is the only FDA approved treatment for mesothelioma and is a
      second line agent for treatment of non-small cell lung carcinoma (NSCLC).
      Pemetrexed is inhibited by folate and its analogs, which are components of many
      culture media, making it challenging to study pemetrexed in vitro. In order to
      accurately evaluate pemetrexed's effects in vitro, the protocol for a standard
      chemosensitivity assay, the ChemoFx drug response marker, had to be modified.
      EXPERIMENTAL DESIGN: Novel rinse and media change steps were assessed and then
      added to the assay protocol in order to observe pemetrexed activity. The intraday
      and interday stability of pemetrexed were also established under the adapted
      protocol. Then, the modified protocol was used to examine pemetrexed in 65 ex
      vivo lung cancer specimens. RESULTS: Substituting 5% RPMI + EGF for BEGM allowed
      pemetrexed to exert its anticancer activity in the ChemoFx DRM. ChemoFx
      classified 6.2% of the lung specimens as responsive, 9.2% as intermediate
      responsive and 84.6% as non-responsive to pemetrexed. CONCLUSIONS: Adapting the
      ChemoFx protocol allowed for the accurate evaluation of pemetrexed anticancer
      activity in ex vivo lung specimens. ChemoFx evaluation may provide an indication
      of a patient's clinical response to the drug prior to pemetrexed treatment.
      Having this information when treatment options are being considered could avoid
      wasted time, unnecessary costs and needless side effects that are the result of
      an inappropriate chemotherapy regimen.

PMID- 23114651
TI  - Emergent states in dense systems of active rods: from swarming to turbulence.
AB  - Dense suspensions of self-propelled rod-like particles exhibit a fascinating
      variety of non-equilibrium phenomena. By means of computer simulations of a
      minimal model for rigid self-propelled colloidal rods with variable shape we
      explore the generic diagram of emerging states over a large range of rod
      densities and aspect ratios. The dynamics is studied using a simple numerical
      scheme for the overdamped noiseless frictional dynamics of a many-body system in
      which steric forces are dominant over hydrodynamic ones. The different emergent
      states are identified by various characteristic correlation functions and
      suitable order parameter fields. At low density and aspect ratio, a disordered
      phase with no coherent motion precedes a highly cooperative swarming state with
      giant number fluctuations at large aspect ratio. Conversely, at high densities
      weakly anisometric particles show a distinct jamming transition whereas slender
      particles form dynamic laning patterns. In between there is a large window
      corresponding to strongly vortical, turbulent flow. The different dynamical
      states should be verifiable in systems of swimming bacteria and artificial rod
      like micro-swimmers.

PMID- 23114650
TI  - Divergent control of Cav-1 expression in non-cancerous Li-Fraumeni syndrome and
      human cancer cell lines.
AB  - Li-Fraumeni syndrome (LFS) is primarily characterized by development of tumors
      exhibiting germ-line mutations in the p53 gene. Cell lines developed from
      patients of a LFS family have decreased p53 activity as evidenced by the absence
      of apoptosis upon etoposide treatment. To test our hypothesis that changes in
      gene expression beyond p53 per se are contributing to the development of tumors,
      we compared gene expression in non-cancerous skin fibroblasts of LFS-affected
      (p53 heterozygous) vs. non-affected (p53 wild-type homozygous) family members.
      Expression analysis showed that several genes were differentially regulated in
      the p53 homozygous and heterozygous cell lines. We were particularly intrigued by
      the decreased expression (~88%) of a putative tumor-suppressor protein, caveolin
      1 (Cav-1), in the p53-mutant cells. Decreased expression of Cav-1 was also seen
      in both p53-knockout and p21-knockout HTC116 cells suggesting that p53 controls
      Cav-1 expression through p21 and leading to the speculation that p53, Cav-1 and
      p21 may be part of a positive auto-regulatory feedback loop. The direct
      relationship between p53 and Cav-1 was also tested with HeLa cells (containing
      inactive p53), which expressed a significantly lower Cav-1 protein. A panel of
      nonfunctional and p53-deficient colon and epithelial breast cancer cell lines
      showed undetectable expression of Cav-1 supporting the role of p53 in the control
      of Cav-1. However, in two aggressively metastasizing breast cancer cell lines,
      Cav-1 was strongly expressed suggesting a possible role in tumor metastasis.
      Thus, there is a divergent control of Cav-1 expression as evidenced in non
      cancerous Li-Fraumeni syndrome and some aggressive human cancer cell lines.

PMID- 23114652
TI  - Sodium disorders in the emergency department: a review of hyponatremia and
      hypernatremia.
AB  - Identifying and correcting sodium abnormalities is critical, since suboptimal
      management potentially leads to substantial morbidity and mortality.
      Manifestations of hyponatremia, which is one of the more common electrolyte
      abnormalities in clinical medicine, depend on multiple factors, including the
      chronicity of the symptoms, the absolute level of sodium, and the patient's
      overall health. In symptomatic hyponatremia, emergency clinicians must understand
      the importance of determining the proper rate of sodium correction in order to
      avoid encephalopathy, cerebral edema, and death. Hypernatremia is most often due
      to unreplaced water that is lost from the gastrointestinal tract, skin, or the
      urine. Acute symptomatic hypernatremia should be corrected rapidly, while chronic
      hypernatremia is generally corrected more slowly due to the risks of brain edema
      during treatment. Special circumstances do exist in sodium management, and every
      patient's presentation should be evaluated in clinical context.

PMID- 23114653
TI  - The effects of the 11 kDa protein and the putative X protein on the p6 promoter
      activity of Parvovirus B19 in Hela cells.
AB  - Human parvovirus B19 (B19) is a small nonenveloped icosahedral virus with a
      single-stranded, linear 5.6 kb DNA genome. The p6 promoter, at map unit 6 of the
      viral genome, controls the expression of all B19 transcripts. Some previous
      reports revealed that this promoter is transactivated by NS1 protein. In an
      attempt to investigate the roles of other small viral proteins in the control of
      the p6 promoter activity, various truncated promoter/reporter constructs along
      with these nonstructural protein expression vectors were introduced into Hela
      cells. The results showed that the putative X protein upregulated the activity of
      p6 promoter significantly, but that the 11 kDa protein did not. Furthermore, the
      possible responsive DNA elements for X protein were identified to be located
      primarily between nt 265 and 343 of the p6 promoter region. In addition, we
      observed that deletion of the potential ATF/CREB binding sites located in 5'
      terminal nucleotide influenced the activity of p6 promoter significantly.

PMID- 23114654
TI  - GS-1101: a delta-specific PI3K inhibitor in chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) remains an incurable B-cell malignancy with
      many unanswered questions. While the cell of origin and etiology are still
      unknown, significant scientific progress has revealed numerous molecular targets
      for novel therapeutic interventions. Phosphatidylinositol 3-kinases (PI3K)
      regulate key cellular functions, including growth, survival and migration, by
      integrating and transmitting signals from diverse surface molecules including the
      B-cell receptor (BCR). In lymphocytes, the PI3Kdelta isoform plays a critical
      role in B-cell homeostasis and function. In CLL, the PI3K pathway is
      constitutively active and dependent on PI3Kdelta. GS-1101 is a highly selective
      PI3Kdelta inhibitor that in CLL patients causes a rapid and sustained reduction
      in lymphadenopathy, accompanied by transient lymphocytosis. This article will
      review new insights into the pathophysiology of CLL, the preclinical rationale of
      a PI3Kdelta inhibitor in CLL, and the clinical evidence supporting this first-in
      class therapeutic target for CLL patients.

PMID- 23114655
TI  - Formation of SERS active nanoparticle assemblies via specific carbohydrate
      protein interactions.
AB  - An on/off SERS aggregation system has been designed to investigate carbohydrate
      lectin interactions. Detection of the lectin ConA was achieved at pico molar
      levels. Discrimination was also demonstrated between two different carbohydrate
      moieties demonstrating the specific interaction between the carbohydrate and
      specific protein present.

PMID- 23114657
TI  - Description of larva of Amblyomma romitii (Acari: Ixodidae) by optical and
      scanning electron microscopy, including porotaxy and phylogenetic analysis.
AB  - The description of the larva of Amblyomma romitii Tonelli-Rondelli is based on
      optical and scanning electron microscopy. Larvae were obtained under laboratory
      conditions from an engorged female collected on capybara from Ruropolis
      municipality, State of Para, Northern Brazil. Several characters are presented
      including the chaetotaxy of idiosoma, palpi and Haller's organ. The larval
      porotaxy (topographical and numerical patterns of integumentary structures) was
      presented and compared to that of the other Amblyomma spp. larvae. The
      mitochondrial 16S rDNA partial sequence of A. romitii generated in the present
      study was aligned with sequences previously determined for other Amblyomma
      species available in Genbank and with some species presently sequenced. The
      larval morphology of A. romitii and other Neotropical Amblyomma spp. larvae is
      discussed as well as the DNA sequence and its phylogenetic position among other
      species of the genus.

PMID- 23114658
TI  - [Septic hip joint surgery].

PMID- 23114659
TI  - [Arthroscopic therapy algorithm for septic coxitis].
AB  - Septic coxitis is a potentially life-threatening disease which necessitates an
      early diagnosis and effective treatment to ensure preservation of joint integrity
      and function. The hip joint is the second most frequently affected joint exceeded
      only by the knee. In adult patients septic coxitis has a hematogenous and
      iatrogenic origin in approximately 50 % of cases each (after intra-articular
      injection and surgery) but in children hematogenous infections are the most
      common. Septic arthritis of the hip leads to severe functional loss in up to 25%
      of patients.  The treatment consists of systemic antibiotic therapy and stage
      adjusted surgical procedures whereby arthroscopic treatment is a promising
      minimally invasive option for treatment in both children and adults.

PMID- 23114660
TI  - [Differential diagnosis of inflammatory arthritis of the hip joint].
AB  - The differential diagnosis of inflammatory arthritis of the hip covers a broad
      spectrum and includes in particular crystal arthropathies and systemic rheumatic
      diseases. The clinical examination of joint effusion of the hip may be difficult
      but diagnostic ultrasound should support an early diagnosis. Radiographs remain
      essential in the initial diagnostic evaluation but may be of limited value in
      early stages of the disease. Magnet resonance imaging may be helpful in addition
      for the detection of early arthritis.Basic laboratory diagnostics include blood
      count, determination of C-reactive protein level and erythrocyte sedimentation
      rate. If septic arthritis is suspected blood cultures should be taken. Joint
      aspiration should be attempted in all cases and especially in monoarthritis.
      Synovial fluid analysis includes white cell count, differential count,
      examination for crystals and microbiological diagnostics including direct stains
      and cultures. The most important differential diagnoses of inflammatory arthritis
      of the hip joint in adults are osteoarthritis, crystal arthropathies and systemic
      rheumatic diseases, such as spondyloarthritis.

PMID- 23114661
TI  - [Adult onset septic coxitis : etiology, diagnostics, indication for and technique
      of open revision of the hip].
AB  - Septic arthritis of the hip can be caused via a hematogenous route, by
      penetration of periarticular infections, open hip trauma, injections or
      operations. Ultrasound, hip puncture and elevation of inflammatory parameters
      lead to the diagnosis. Differentiation of septic arthritis from gout and
      chondrocalcinosis may be difficult. Nevertheless, early revision of the hip has
      to be performed to avoid joint destruction. Open revision is the therapy of
      choice in the majority of cases.

PMID- 23114662
TI  - [Operative versus nonoperative treatment of displaced midshaft clavicular
      fractures : a meta-analysis of randomized clinical trials].

PMID- 23114664
TI  - Neuroschistosomiasis mansoni: literature review and guidelines.
AB  - BACKGROUND: Schistosomiasis is a tropical disease caused by worms of the genus
      Schistosoma. It is endemic in the Caribbean Islands, the middle east, eastern
      Asia, South America, and Africa. In nonendemic areas, physicians should be aware
      of this condition in travelers returning from endemic areas and in immigrants.
      The main disease-causing species are Schistosoma haematobium, Schistosoma
      mansoni, and Schistosoma japonicum. Neuroschistosomiasis is an ectopic form of
      the disease that is mainly associated with S. japonicum infection. Involvement of
      the central nervous system (CNS) in S. mansoni infection is neglected and
      underestimated. Neuroschistosomiasis mansoni can be classified into cerebral,
      spinal, and encephalomyelitic forms in the course of an acute or chronic
      infection. REVIEW SUMMARY: We review the CNS involvement by S. mansoni infection
      with an emphasis on life cycle, epidemiology, pathophysiology and immunology,
      clinical manifestations, diagnostic criteria, differential diagnosis, current
      treatment guidelines, and prognosis. CONCLUSIONS: Although an underreported CNS
      infection, found mainly in underdeveloped countries, neuroschistosomiasis mansoni
      still causes significant incapacity and morbidity. Hence, neurologists should
      become familiar with this infection worldwide and include it in the differential
      diagnosis of CNS involvement in travelers returning from endemic areas and in
      immigrants.

PMID- 23114663
TI  - Effects of a competitive wrestling season on body composition, endocrine markers,
      and anaerobic exercise performance in NCAA collegiate wrestlers.
AB  - Few data exist examining the body composition, endocrine, and anaerobic exercise
      performance changes over a competitive wrestling season. Eighteen NCAA wrestlers
      were tested for endocrine markers, body composition, hydration, grip strength,
      and power on four occasions: prior to pre-season training (T1); after pre-season
      training 3 days prior to the first seasonal meet (T2); mid-season one day prior
      to a meet (T3); and at the end of the season 2-3 days following the last meet
      (T4). Body mass, percent body fat (BF %), and fat mass were significantly lower
      (P <= 0.05) at T2 and T3 compared to T1 but were not different between T1 and T4.
      Lean body mass was significantly reduced at T2 only. Urine specific gravity was
      significantly elevated at T3 compared to T1, T2, and T4. Resting cortisol
      concentrations did not change but resting testosterone concentrations were
      significantly reduced at T2, T3, and T4. Maximal grip strength was significantly
      reduced at T2. Vertical jump peak power was significantly reduced at T2, T3, and
      T4. Wingate peak power was significantly reduced at T2 and T3. However, Wingate
      average power and total work did not significantly change. Fatigue rate during
      the Wingate test was significantly improved at T2, T3, and T4 compared to T1. In
      conclusion, body mass, BF %, and measures of peak force and power were reduced
      for most of the competitive wrestling season. Competitive wrestling reduces
      resting total testosterone concentrations throughout the entire season.

PMID- 23114665
TI  - Nocturnal frontal lobe epilepsy and the acetylcholine receptor.
AB  - BACKGROUND: Nocturnal frontal lobe epilepsy (NFLE) is an idiopathic partial
      epilepsy characterized by a wide spectrum of stereotyped motor manifestations,
      mostly occurring during non rapid eye movements sleep. NFLE is underdiagnosed
      since semiological similarities make it difficult to distinguish NFLE from
      parasomnias. In 1994, authors reported families with NFLE inherited as an
      autosomal dominant trait and they introduced the term of autosomal dominant
      nocturnal frontal lobe epilepsy (ADNFLE). A family history of possible NFLE is
      found in about 25% of cases. The genetic bases of the disease have been detected
      in a minority of cases. Mutations causing a gain of function of the neuronal
      nicotinic acetylcholine receptors were reported in 3 different subunits. REVIEW
      SUMMARY: This review discusses the clinical aspects of NFLE and the diagnostic
      procedures. Furthermore, the genetic aspects are outlined. The main
      differentiating features characterizing NFLE are: (a) several attacks per night
      at any time during the night; (b) brief duration of the attacks; (c) stereotyped
      motor pattern. Nocturnal video-polysomnography is crucial for the diagnosis.
      Neurological examination in NFLE/ADNFLE is normal. About 30% of NFLE cases are
      resistant to antiepileptic drugs. Concerning the genetics, putative
      susceptibility nucleotide variations affecting the promoter of the CRH gene and
      altering the corticotrophin-releasing hormone levels have been reported in some
      NFLE patients. CONCLUSIONS: Distinguishing NFLE seizures from paroxysmal
      nonepileptic sleep disorders is often difficult and sometimes impossible on
      clinical grounds alone. Nocturnal video-polysomnography is mandatory. Further
      genetic studies could help the diagnosis and treatment in NFLE patients.

PMID- 23114667
TI  - New criteria for Alzheimer disease and mild cognitive impairment: implications
      for the practicing clinician.
AB  - BACKGROUND: In most research studies and clinical trials, Alzheimer disease (AD)
      has been diagnosed using the criteria developed by the National Institute of
      Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease
      and Related Disorders Association work group in 1984. Developments over the last
      27 years have lead to the need for new diagnostic criteria. REVIEW SUMMARY: Four
      articles in the journal Alzheimer's & Dementia in 2011 describe new criteria for
      AD dementia and mild cognitive impairment (MCI) due to the AD pathophysiological
      process (MCI due to AD) and the underlying rationale for them. These new criteria
      emphasize that the AD pathophysiological process starts years and perhaps decades
      before clinical symptoms, and that biomarkers can be used to detect amyloid beta
      deposition and the effects of neurodegeneration in the brain. CONCLUSIONS: These
      new criteria are immediately helpful to the practicing clinician, providing more
      accurate and specific guidelines for the diagnosis of AD dementia and MCI due to
      AD. As new diagnostic tools and new treatments for AD become available, diagnosis
      using these criteria will enable patients with this disorder to receive the best
      possible care.

PMID- 23114666
TI  - The use of retinal photography in nonophthalmic settings and its potential for
      neurology.
AB  - BACKGROUND: Ocular fundus examination is an important element of the neurological
      examination. However, direct ophthalmoscopy is difficult to perform without
      pupillary dilation and requires extensive practice to accurately recognize optic
      nerve and retinal abnormalities. Recent studies have suggested that digital
      retinal photography can replace direct ophthalmoscopy in many settings. REVIEW
      SUMMARY: Ocular fundus imaging is routinely used to document and monitor disease
      progression in ophthalmology. Advances in optical technology have made it easier
      to obtain high-quality retinal imaging, even without pupillary dilation. Retinal
      photography has a high sensitivity, specificity, and
      interexamination/intraexamination agreement compared with in-person
      ophthalmologist examination, suggesting that photographs can be used in lieu of
      ophthalmoscopy in many clinical situations. Nonmydriatic retinal photography has
      recently gained relevance as a helpful tool for diagnosing neuro-ophthalmologic
      disorders in the emergency department. In addition, several population-based
      studies have used retinal imaging to relate ophthalmic abnormalities to the risk
      of hypertension, renal dysfunction, cardiovascular mortality, subclinical and
      clinical stroke, and cognitive impairment. The possibility of telemedical
      consultation offered by digital retinal photography has already increased access
      to timely and accurate subspecialty care, particularly for underserved areas.
      CONCLUSIONS: Retinal photography (even without pupillary dilation) has become
      increasingly available to medical fields outside of ophthalmology, allowing for
      faster and more accurate diagnosis of various ocular, neurological, and systemic
      disorders. The potential for telemedicine may provide the additional benefits of
      improving access to appropriate urgent consultation in both clinical and research
      settings.

PMID- 23114668
TI  - Cognitive behavioral therapy for psychogenic neurological disorders.
AB  - BACKGROUND: Psychogenic neurological disorders (PNDs) represent a significant
      problem in neurology, due to the difficulty in diagnosis and lack of effective
      and widely available treatment options. Treatment options for this population are
      limited. Preliminary evidence reveals cognitive behavioral therapy (CBT) may be
      useful in these disorders. REVIEW SUMMARY: The types of PNDs and their
      presentations are summarized, and the utilization of CBT in treatment of these
      disorders is reviewed. Accurate and timely diagnosis of the disorders is
      paramount and provides direction for implementing appropriate treatment.
      CONCLUSIONS: Neurologists should be familiar with the types of PNDs, clinical
      findings, and treatment principles of CBT. Early and accurate diagnosis may lead
      to improved treatment outcomes. Controlled treatment trials for this population
      are needed to determine efficacy. Further study of CBT in these patients may also
      help to elucidate the underlying etiology of these disorders by contributing to
      the understanding of associated psychopathology.

PMID- 23114669
TI  - Isolated neurosarcoidosis: case series in 2 sarcoidosis centers.
AB  - BACKGROUND: Neurosarcoidosis occurs in the central or peripheral nervous system
      and is usually associated with other sarcoidosis organ involvement. However, when
      sarcoidosis develops exclusively in the nervous system, its diagnosis is
      problematic. METHODS: Retrospective analysis of patients who were histologically
      diagnosed with neurosarcoidosis without other organ involvement (isolated
      neurosarcoidosis) at Medical University of South Carolina and Allegheny General
      Hospital. For comparison, we also collected data from neurosarcoidosis patients
      with histologic evidence in an extraneural organ (systemic neurosarcoidosis).
      RESULTS: Ninety-one cases of neurosarcoidosis were identified with 10 patients
      having isolated neurosarcoidosis. Common clinical manifestations of the isolated
      neurosarcoidosis patients were headache (9), paresthesia (5), and cranial
      neuropathies (4). All isolated neurosarcoidosis patients underwent a biopsy from
      the central nervous system. The prebiopsy impression included lymphoma (4), tumor
      (2), and sarcoidosis (2). In all patients, no extranueral sarcoidosis developed
      during a relatively long follow-up period (mean 58 mo). Compared with the
      systemic neurosarcoidosis cohort (60), isolated neurosarcoidosis patients had
      similar demographics and neurological manifestations with a few exceptions
      including a more common frequency of headache, hemiparesis, and radiculopathy,
      leptomeningeal involvement on brain MRI, increased cell count in cerebrospinal
      fluid, and a more favorable clinical outcome (P<0.05). The duration of follow-up
      and the number of studies performed to evaluate patients for extraneural
      sarcoidosis were similar in the 2 cohorts. CONCLUSIONS: The clinical and
      radiologic features of isolated neurosarcoidosis are similar to those of systemic
      neurosarcoidosis with a few exceptions. The diagnosis of isolated
      neurosarcoidosis is problematic and often not considered before biopsy of neural
      tissue.

PMID- 23114670
TI  - Clinical spectrum and evolution of monoclonal gammopathy-associated neuropathy:
      an observational study.
AB  - BACKGROUND: Paraproteinemic neuropathy (PPN) is often under-diagnosed because of
      its clinical and electrophysiological variability. Progression of neuropathy is
      considered an alarm bell for possible malignant conversion of underlying
      monoclonal gammopathy (MG). OBJECTIVE: To report clinical presentation, course,
      and evolution in a group of patients with PPN in order to identify findings
      useful for achieving the diagnosis, suspecting progression, and recognizing the
      underlying hematological conditions. PATIENTS AND METHODS: Thirty-nine patients
      with PPN underwent clinical examination, electrodiagnostic studies, cerebrospinal
      fluid analysis, and laboratory tests. These parameters were compared between the
      different peak groups. RESULTS: IgM MG was found in 51.4%, IgG MG in 33.3%, and
      IgA MG in 10.3% of our cohort. PPN appeared as mainly sensory, demyelinating,
      mildly progressive neuropathy, regardless of the type of peak or light chain.
      However, axonal findings were present in many IgG patients and in part of the IgM
      patients and a small number of the IgG patients may have presented with motor
      symptoms at the onset. The IgM patients had a significant tendency toward
      clinical worsening and IgG subjects had a more elevated rate of malignancy. IgA
      related neuropathies were rare, heterogenous, and with a high tendency to
      evolution and malignancy. CONCLUSIONS: Most of PPN often present a relatively
      monomorphic clinical picture but they can be clinically heterogenous and must be
      suspected even if sensory impairment and demyelination are not the dominant
      features. Tendency to malignancy seems globally elevated and needs intensive
      follow-up. Diagnostic approach to patients presenting with peripheral neuropathy
      should always include the typing of monoclonal immunoglobulins in serum and
      urine. In contrast, patients presenting with MG should be submitted to nerve
      conduction study/electroneurography and neurological evaluation.

PMID- 23114671
TI  - Gentamicin-induced myoclonus: a case report and literature review of antibiotics
      induced myoclonus.
AB  - INTRODUCTION: Drug-induced myoclonus is a diagnosis of exclusion. Various drugs
      have been reported to induce myoclonus. Antibiotic-induced myoclonus (AIM) is
      very rare. We describe a case of multifocal myoclonus secondary to gentamicin
      toxicity and review the literature of AIM. CASE REPORT: A 59-year-old woman with
      end-stage renal disease developed generalized multifocal myoclonus within 1 hour
      after receiving only 1 supratherapeutic dose of gentamicin for a potential
      hemodialysis catheter infection. Myoclonus was completely resolved after 2
      sessions of hemodialysis. We identified 22 patients of AIM in the literature. The
      median age of patients was 63 years. More than half of patients (12/22, 55%) had
      underlying chronic kidney disease. Cephalosporins were the most common drug class
      associated with AIM (12/22 patients; 55%). About two third of patients (15/22,
      68%) received overdoses of antibiotics. Fifteen patients (71%) completely
      recovered after discontinuing or decreasing the dose of antibiotics. Five
      patients (24%) died of underlying medical conditions or of unknown etiology. Only
      1 had persistent myoclonus. The potential mechanisms of AIM are discussed.
      CONCLUSIONS: AIM, although rare, should be considered as a potential cause of
      multifocal myoclonus in patients with advanced age or renal insufficiency. The
      prognosis of AIM appears favorable, with several cases resolving after withdrawal
      of the antibiotic.

PMID- 23114672
TI  - Local(eyes)ing signs in sequential bihemispheric strokes.
AB  - INTRODUCTION: Decerebrate posturing typically occurs in the setting of midbrain
      injury. However, it may also be seen as the result of massive bilateral forebrain
      lesions. The latter localization is supported when seen concomitantly with roving
      eye movements and normal brainstem reflexes. CASE REPORT: A 61-year-old woman
      developed aphasia and right hemiparesis and was found to have a left anterior
      middle cerebral artery stroke from atrial fibrillation. The following day, her
      examination quickly deteriorated from mild aphasia and right hemiparesis to coma,
      right gaze preference alternating with roving eye movements, and decerebrate
      posturing. Electroencephalography showed bihemispheric dysfunction, and magnetic
      resonance imaging showed new scattered right middle cerebral artery territory
      infarcts. She was found to have right A1 and M1 occlusions, and recanalization
      was achieved with intra-arterial tissue plasminogen activator. CONCLUSIONS: This
      case highlights the localizing value of the constellation of coma, a gaze
      preference alternating with roving eye movements, and decerebrate posturing
      through a discussion of the relevant neuroanatomy and pathophysiology.

PMID- 23114674
TI  - Cystic medionecrosis of the carotid bifurcation as an uncommon cause of stroke.
AB  - BACKGROUND AND PURPOSE: Cystic medionecrosis is characterized by degeneration of
      elastic and collagenous fibers in the media and predominantly involves the
      thoracic aorta. This rare disease is usually manifested clinically by a
      dissecting aneurysm. Cystic medionecrosis as a cause of moderate stenosis of the
      carotid artery in a patient having a stroke has not been reported. SUMMARY OF
      CASE: We report a case of a man who had a cerebral infarction caused by medium
      degree stenosis of the left internal carotid artery. Duplex sonography and
      magnetic resonance imaging revealed no typical signs of dissection. The stenosis
      was caused by cystic medionecrosis that involved only the carotid bifurcation
      with microdissection, predominantly older intramural hemorrhage, and fresh
      intraluminal thrombotic deposits. CONCLUSIONS: Patients with cystic medionecrosis
      may have a stroke due to short-track stenosis of the internal carotid artery.

PMID- 23114673
TI  - Elucidating the mechanism of posterior reversible encephalopathy syndrome: a case
      of transient blindness after central venous catheterization.
AB  - INTRODUCTION: Posterior reversible encephalopathy syndrome (PRES) is a condition
      characterized by reversible symptoms including headache, visual disturbances,
      focal neurological deficits, altered mentation, and seizures. It has been
      associated with circumstances that may affect the cerebrovascular system, such as
      hypertension, eclampsia, and immunosuppression with calcineurin inhibitors. The
      underlying etiology of PRES has remained unclear; however, cerebrovascular
      autoregulatory dysfunction, hyperperfusion, and endothelial activation have been
      implicated. CASE REPORT: We describe a case of a young patient with lung
      transplant, who presented with headache, acute binocular blindness, and seizure
      immediately after infusion of saline through a peripherally inserted central
      catheter line, which inadvertently terminated cephalad in the left internal
      jugular vein, near the jugular foramen. Subsequent brain magnetic resonance
      imaging revealed vasogenic edematous lesions in a pattern consistent with PRES--a
      diagnosis supported by his constellation of symptoms, history of lung
      transplantation on tacrolimus immunosuppression, and relative hypertension.
      CONCLUSIONS: This is the first reported case describing the development of PRES
      after the insertion of a peripherally inserted central catheter line. The
      development of PRES in a typical high-risk patient immediately after cerebral
      venous outflow obstruction implicates the role of the cerebral venous system and
      provides potential insight into the mechanism of this disorder that remains of
      unclear pathogenesis.

PMID- 23114675
TI  - Moyamoya disease can masquerade as multiple sclerosis.
AB  - BACKGROUND: Moyamoya disease (MM) is a rare disorder of the cerebral arterial
      circulation, whereas multiple sclerosis (MS) is a relatively common immune
      mediated attack on central myelin. Despite the differences in pathogenesis, the 2
      disorders share some clinical features which can lead to diagnostic confusion:
      both can affect young adults, cause intermittent neurological symptoms, and show
      multifocal abnormalities on brain imaging. OBJECTIVE: To emphasize the need for
      early consideration of MM in the differential diagnosis of MS-spectrum disorders.
      METHODS: Chart reviews and individual case analyses. RESULTS: We present detailed
      descriptions of 3 patients with MM, and summary data on 8 additional cases, in
      which there was diagnostic confusion with MS, with delays in treatment ranging
      from 2 months to 19 years (median=4 y). CONCLUSIONS: MM can be misdiagnosed as
      MS, leading to delay in correct treatment. We highlight the clinical and
      radiologic features which allow differentiation of these conditions early in the
      course, when treatment can have maximum benefit.

PMID- 23114676
TI  - Cueing for freezing of gait: a need for 3-dimensional cues?
AB  - Visual cues can ameliorate freezing of gait, an incapacitating symptom frequently
      seen in patients with parkinsonism. Here, we describe a patient with severe
      freezing of gait, who responded well to 3-dimensional cues, but not to 2
      dimensional visual cues. We discuss the potential implications of this
      phenomenon.

PMID- 23114677
TI  - Recurrent horner syndrome and persistent trigeminal artery.
AB  - INTRODUCTION: A persistent primitive trigeminal artery (PTA) is the most common
      type of fetal carotid-basilar anastomosis in adulthood; however, its prevalence
      is low and estimated between 0.1% and 0.7% in angiographic studies. PTA is
      usually diagnosed incidentally during an angiographic examination, though some
      symptomatic cases associated with cranial nerve dysfunction have been described.
      We describe the unusual association between PTA and ipsilateral Horner syndrome
      triggered by hypertensive crisis. CASE REPORT: A 40-year-old man presented to
      medical attention for recurrent episodes, over the last 3 years, characterized by
      hypertensive crisis (up to 220/150 mm Hg), dizziness, tachycardia, flushing of
      the forehead on the left side, ptosis, miosis, and conjunctival injection of the
      left eye without pain. Imaging revealed a left PTA originating from the carotid
      siphon with moderate ectasia of the proximal tract. We speculate that the
      recurrent Horner syndrome observed in our patient could be due to the disruption
      of the postganglionic peripheral fibers in the pericarotid plexus. Adequate
      antihypertensive therapy led to resolution of signs and symptoms. CONCLUSIONS: To
      our knowledge, we present the first case of persistent PTA and ipsilateral Horner
      syndrome during hypertensive crisis. Adequate antihypertensive therapy can be
      useful in patients bearing trigeminal artery variants.

PMID- 23114678
TI  - Rapid symptomatic and radiographic evolution after presumed spontaneous
      infarction of a meningioma.
AB  - Meningiomas are extremely common benign extra-axial brain tumors. When
      meningiomas present clinically, they typically cause subacute symptoms such as
      headache. Rarely, meningiomas become acutely symptomatic due to tumor necrosis,
      which may occur spontaneously or as a result of global hypoperfusion. Here, we
      describe an elderly man who experienced a rapid subacute decline after meningioma
      infarction. Computed tomography and magnetic resonance imaging obtained in this
      case demonstrate the evolution of a benign-appearing meningioma into a ring
      enhancing lesion with significant surrounding cerebral edema in <2 weeks. After
      the resection of a WHO grade 1 meningioma with central necrosis, the patient made
      a good clinical recovery.

PMID- 23114679
TI  - Fabry disease with atypical neurological presentation: report of a case.
AB  - INTRODUCTION: Fabry disease (FD) is a rare, X-linked lysosomal storage disorder
      with multiorgan involvement. FD is caused by a partial or total deficit of alpha
      galactosidase A enzyme, which is responsible for the accumulation of
      glycosphingolipids in a variety of cell types. Neurological complications include
      central nervous system involvement with cerebrovascular disease, peripheral
      neuropathy, and autonomic dysfunction. CASE REPORT: We report the case of a 47
      year-old man with an atypical neurological presentation of FD, characterized by
      48-hour consciousness alteration with amnesia, resembling a long-lasting episode
      of transient global amnesia. CONCLUSIONS: Our case expands the neurological
      presentations associated with FD.

PMID- 23114680
TI  - Acute provoked reflex seizures induced by thinking.
AB  - Thinking epilepsy is a rare form of reflex epilepsy that can be induced by
      specific cognitive tasks, and occurs mainly in idiopathic generalized epilepsies.
      We report a case of complex partial seizures triggered by thinking in a young man
      with acute bacterial meningitis and a remote head injury. This case illustrates
      that thinking-induced reflex seizures can be partial and can be provoked by an
      acute brain insult.

PMID- 23114681
TI  - Localization of bilateral auditory hallucinations and correlation to imaging in
      posterior circulation stroke.
AB  - Hearing disturbances are not commonly reported in stroke or transient ischemic
      attack. We describe a case of a 60-year-old man with fluctuating brainstem
      ischemia with basilar artery thrombosis where the patient has consistently
      described hearing "white noise," bilaterally becoming progressively louder over
      10 minutes that prevented him from hearing surrounding noise including the radio.
      These episodes were transient and preceded episodes of hemiparesis or reduced
      conscious level. We correlate this to the sequential imaging findings from the
      patient. We discuss how this case provides in vivo evidence for localization of
      auditory hallucinations in the context of the auditory pathways and their blood
      supply, and review 25 previous cases of auditory hallucinations and possible
      mechanisms.

PMID- 23114682
TI  - An extreme case of the syndrome of the trephined requiring the use of a novel
      titanium plate.
AB  - INTRODUCTION: Patients with large cranial defects can manifest a secondary
      neurological deterioration known as the "syndrome of the trephined." CASE REPORT:
      This is the case of a 66-year-old female with a left-sided acute subdural
      hematoma, treated with decompressive craniectomy. Six months later, a
      cranioplasty was performed. However, it was complicated by an infection requiring
      removal of the bone plate. A week later, the patient became comatose; her
      craniectomy flap was sunken. After ruling out all other possible disorders, we
      suspected an extreme syndrome of the trephined. The patient's neurological status
      drastically improved after she was placed on a Trendelenburg position regiment. A
      second cranioplasty was performed only 3 months after the infection using a novel
      custom designed titanium mesh, the least porous material used in synthetic bone
      flaps, to decrease the risk of infection. The patient had an excellent recovery;
      at her 6-month follow-up she was neurologically intact, cosmetically satisfied,
      and free of infection. CONCLUSIONS: The treatment of extreme cases of syndrome of
      the trephined in the setting of a recent infection can be challenging; successful
      treatment can be achieved by using a custom titanium plate.

PMID- 23114683
TI  - Disrupted daytime activity and altered sleep-wake patterns may predict transition
      to mild cognitive impairment or dementia: a critically appraised topic.
AB  - BACKGROUND: There is a well-known relationship between neurodegenerative disease,
      disrupted sleep, and cognition. Pathologic and imaging studies have shown that
      regions in the brain shown to regulate sleep and circadian rhythm are abnormal in
      Alzheimer disease. Most of these studies have been cross-sectional, and often
      look at patients already with dementia. This leaves uncertainty with regard to
      the temporal relationship of circadian disruption and cognitive decline.
      OBJECTIVE: To determine whether disrupted daytime activity and altered sleep
      patterns predict development of mild cognitive impairment (MCI) or dementia.
      METHODS: The objective was addressed through the development of a structured,
      critically-appraised topic. We incorporated a clinical scenario, background
      information, a structured question, literature search strategy, critical
      appraisal, results, evidence summary, commentary, and bottom line conclusions.
      Participants included consultant and resident neurologists, a medical librarian,
      and behavioral neurology and sleep medicine content experts. RESULTS: A
      prospective cohort study of 1282 cognitively normal women demonstrated that when
      peak circadian activity, as measured by wrist actigraphy, occurred later than
      average, there was an increased risk of MCI or dementia [odds ratio (OR), 1.83;
      95% confidence interval (CI), 1.29-2.61]. Increased odds for dementia or MCI also
      existed for those with decreased circadian rhythm amplitude (OR, 1.57; 95% CI,
      1.09-2.25) and robustness (OR, 1.57; 95% CI, 1.29-2.61). CONCLUSIONS: Disrupted
      circadian rhythm measures, including lower amplitude, a less robust rhythm, and
      delayed timing of peak activity on wrist actigraphy, were predictive of future
      development of MCI or dementia in cognitively normal women.

PMID- 23114684
TI  - Drugs for some common eye disorders.

PMID- 23114685
TI  - Absorption spectra of natural pigments as sensitizers in solar cells by TD-DFT
      and MRPT2: protonated cyanidin.
AB  - The study of molecular species suitable as sensitizers in solar cells involves
      the understanding of their visible absorption spectrum. In this article we
      present a detailed theoretical study of the visible band which has been observed
      for cyanidin in acid solution. We performed accurate DFT and MRPT2 calculations
      on the protonated cyanidin in vacuo and in solution, where we have also computed
      the lineshape profile by including the effects of nuclear degrees of freedom in
      the harmonic approximation.

PMID- 23114686
TI  - Effect of repeated sodium phosphate loading on cycling time-trial performance and
      VO2peak.
AB  - Research into supplementation with sodium phosphate has not investigated the
      effects of a repeated supplementation phase. Therefore, this study examined the
      potential additive effects of repeated sodium phosphate (SP) supplementation on
      cycling time-trial performance and peak oxygen uptake (VO2peak). Trained male
      cyclists (N = 9, M +/- SD VO2peak = 65.2 +/- 4.8 ml . kg-1 . min-1) completed
      baseline 1,000-kJ time-trial and VO2peak tests separated by 48 hr, then ingested
      either 50 mg . kg fat-free mass-1 . d-1 of tribasic SP or a combined glucose and
      NaCl placebo for 6 d before performing these tests again. A 14-d washout period
      separated the end of one loading phase and the start of the next, with 2 SP and 1
      placebo phase completed in a counterbalanced order. Although time-trial
      performance (55.3-56.5 min) was shorter in SP1 and SP2 (~60-70 s), effect sizes
      and smallest-worthwhile-change values did not differ in comparison with baseline
      and placebo. However, mean power output was greater than placebo during time
      trial performance at the 250-kJ and 500-kJ time points (p < .05) after the second
      SP phase. Furthermore, mean VO2peak values (p < .01) were greater after the SP1
      (3.5-4.3%), with further improvements (p < .01) found in SP2 (7.1-7.7%), compared
      with baseline and placebo. In summary, repeated SP supplementation, ingested
      either 15 or 35 d after initial loading, can have an additive effect on VO2peak
      and possibly time-trial performance.

PMID- 23114687
TI  - A genetic variant of FcgammaRIIIa is strongly associatedwith humoral immunity to
      cyclin B1 in African American patients with prostate cancer.
AB  - There are significant inter-individual differences in naturally occurring
      antibody responses to the tumor-associated antigen cyclin B1 in healthy subjects
      with no history of cancer as well as in patients with multiple types of cancer,
      but the host genetic factors that might contribute to these differences have not
      been identified. The aim of the present investigation was to determine whether
      the variation in endogenous antibody levels to cyclin B1 in patients with
      prostate cancer was associated with immunoglobulin GM and KM alleles, expressed
      on the constant regions of gamma and kappa chains, respectively. We also aimed to
      determine whether particular Fcgamma receptor (FcgammaR) genotypes, which have
      been implicated in the immunobiology of several cancers, contribute to the
      magnitude of humoral immunity to cyclin B1. DNA samples from 129 Caucasian
      American (CA) and 76 African American (AA) patients with prostate cancer were
      genotyped for several GM, KM, and FcgammaR alleles. Plasma samples from these
      subjects were also characterized for IgG antibodies to cyclin B1. No significant
      associations were found between any genetic markers and the level of anticyclin
      B1 antibodies in CA patients. In AA patients, however, homozygosity for the
      valine allele at the FcgammaRIIIa locus was strongly associated with low antibody
      responsiveness to cyclin B1 (p = 0.0007). Since immunity to cyclin B1 has been
      shown to play a protective role, these results may, at least in part, explain the
      disproportionately higher rate of mortality in AA patients with prostate cancer.

PMID- 23114689
TI  - [Researcher of the month, October 2012].

PMID- 23114690
TI  - Undocumented immigration status and diabetes care among Mexican immigrants in two
      immigration "sanctuary" areas.
AB  - The objective of this study is to investigate the relationship between
      immigration status and the patient experience of health care, diabetes self
      management, and clinical outcomes among Mexican immigrants with diabetes
      receiving health care in two immigration sanctuary cities. We used data from the
      Immigration, Culture and Health Care study, a cross-sectional survey and medical
      record study of low-income patients with diabetes recruited from public hospitals
      and community clinics in the San Francisco Bay Area and Chicago. Undocumented
      Mexican, documented Mexican immigrants, and US-born Mexican-Americans' health
      care experiences, diabetes self-management, and clinical outcomes were compared
      using multivariate linear and logistic regressions. We found no significant
      differences in reports of physician communication, or in measures of diabetes
      management between undocumented and documented immigrants. All three groups had
      similar clinical outcomes in glycemic, systolic blood pressure, and lipid
      control. These results indicate that, at least in some settings, undocumented
      Mexican immigrants with diabetes can achieve similar clinical outcomes and report
      similar health care experiences as documented immigrants and US-born Mexican
      Americans. 

PMID- 23114691
TI  - Probing a highly efficient dual mode: down-upconversion luminescence and
      temperature sensing performance of rare-earth oxide phosphors.
AB  - A dual mode rare-earth based oxide phosphor (Y(0.977)Yb(0.02)Er(0.003)NbO(4)),
      demonstrating both down conversion (DC) and upconversion (UC) emission, has been
      developed using a facile solid state reaction method which can be easily scaled
      up for large quantities. In the DC studies, the material exhibits a strong blue
      emission with a long decay time (4.36 MUs), corresponding to the charge transfer
      band of [NbO(4)](3-) under UV excitation (262 nm), and a green emission of the
      Er(3+) ions under blue (379 nm) excitation. Furthermore, it has been noticed that
      under infrared (976 nm) excitation, this phosphor shows strong green and red
      emission along with relatively weak emission bands in the UV-blue and IR regions,
      which confirm the compatibility of this phosphor for UC too. In the UC emission,
      the (2)H(11/2)    ->    (4)I(15/2) and (4)S(3/2)    ->    (4)I(15/2) transitions
      of the Er(3+) ion portray a temperature dependent behaviour and have been used
      for temperature sensing (optical thermometry) using the fluorescence intensity
      ratio (FIR) method. The maximum sensitivity is found to be 0.0073 K(-1) at 473 K,
      which is better in comparison with other host matrixs reported so far. The
      results suggest that this dual mode phosphor could be an exceptional choice for
      next generation luminescence-based temperature sensing devices as well as in
      advanced display devices.

PMID- 23114692
TI  - Contextual Pavlovian conditioning in the crab Chasmagnathus.
AB  - In contextual conditioning, a complex pattern of information is processed to
      associate the characteristics of a particular place with incentive or aversive
      reinforcements. This type of learning has been widely studied in mammals, but
      studies of other taxa are scarce. The context-signal memory (CSM) paradigm of the
      crab Chasmagnathus has been extensively used as a model of learning and memory.
      Although initially interpreted as habituation, some characteristics of contextual
      conditioning have been described. However, no anticipatory response has been
      detected for animals exposed to the training context. Thus, CSM could be
      interpreted either as an associative habituation or as contextual conditioning
      that occurs without a context-evoked anticipatory response. Here, we describe a
      training protocol developed for contextual Pavlovian conditioning (CPC). For each
      training trial, the context (conditioned stimulus, CS) was discretely presented
      and finished together with the unconditioned stimulus (US). In agreement with the
      CSM paradigm, a robust freezing response was acquired during the 15 training
      trials, and clear retention was found when tested with the US presentation after
      short (2 and 4 h) and long (1-4 days) delays. This CPC memory showed forward but
      not simultaneous presentation conditioning and was context specific and protein
      synthesis dependent. Additionally, a weak CPC memory was enhanced during
      consolidation. One day after training, CPC was extinguished by repeated CS
      presentation, while one presentation induced a memory labilisation
      reconsolidation process. Finally, we found an anticipatory conditioned response
      (CR) during the CS presentation for both short-term (4 h) and long-term memory
      (24 h). These findings support the conditioning nature of the new paradigm.

PMID- 23114693
TI  - Direct synthesis of sensitive selenocysteine peptides by the Ugi reaction.
AB  - Ammonia and selenoaldehydes are both problematic components in Ugi reactions.
      Here we report the efficient direct multicomponent synthesis of sensitive
      selenocysteine peptides without the use of convertible (protected) primary
      amines, including suitable deprotection protocols for selenols.

PMID- 23114695
TI  - An extremely alkaline novel xylanase from a newly isolated Streptomyces strain
      cultivated in corncob medium.
AB  - Streptomyces sp. CS802, recently isolated from Korean soil, produced xylanase in
      corncob medium. An extracellular xylanase (Xyn802) was purified by a single-step
      gel filtration and biochemical properties were studied. It showed high activity
      in extremely alkaline condition with optimum pH at 12.0 and exhibited stability
      between pH 7.5 and 13.0. It produced xylobiose and xylotriose as the major
      products from xylan, suggesting its endoxylanase nature. N-terminal amino acid
      sequences of Xyn802 were ADRNANRD which are significantly different from the
      reported xylanase. The activity was enhanced by various detergents and a reducing
      agent and stable in various organic solvents. Xyn802 produced by utilizing
      corncob, an agro-waste material, might be a novel xylanase based on its peculiar
      biochemical characteristics, and it can be a suitable candidate for the
      production of xylooligosaccharides including other useful products.

PMID- 23114696
TI  - Measurement of anti-erythropoiesis-stimulating agent IgG4 antibody as an
      indicator of antibody-mediated pure red cell aplasia.
AB  - Patients treated with erythropoietin-based erythropoiesis-stimulating agents
      (ESAs) can develop a rare but life-threatening condition called antibody-mediated
      pure red cell aplasia (amPRCA). The antibody characteristics in a nephrology
      patient with amPRCA include high antibody concentrations with neutralizing
      activity and a mixed IgG subclass including anti-ESA IgG4 antibodies. In
      contrast, anti-ESA IgG4 antibody is generally not detected in baseline samples
      and antibody-positive non-PRCA patients. Therefore, we validated a highly
      sensitive immunoassay on the ImmunoCAP 100 instrument to quantitate anti-ESA IgG4
      antibodies using a human recombinant anti-epoetin alfa (EPO) IgG4 antibody as a
      calibrator. The biotinylated ESA was applied to a streptavidin ImmunoCAP, and
      bound anti-ESA IgG4 antibodies were detected using a beta-galactosidase
      conjugated mouse anti-human IgG4 antibody. The validated assay was used to detect
      anti-ESA IgG4 in amPRCA and non-PRCA patients. The immunoassay detected 15 ng/ml
      of human anti-EPO IgG4 antibody in the presence of a 200 M excess of human anti
      ESA IgG1, IgG2, or IgM antibody and tolerated 2 MUg/ml of soluble erythropoietin.
      All patient samples with confirmed amPRCA had measurable anti-ESA IgG4
      antibodies. In addition, 94% (17/18) of non-PRCA patient samples were antibody
      negative or had below 15 ng/ml of anti-ESA IgG4 antibodies. This novel
      immunoassay can measure low-nanogram quantities of human anti-ESA IgG4 antibodies
      in the presence of other anti-ESA antibodies. An increased concentration of anti
      ESA IgG4 antibody is associated with the development of amPRCA. We propose that
      the measurement of anti-ESA specific IgG4 antibodies may facilitate early
      detection of amPRCA in patients receiving all ESAs structurally related to human
      erythropoietin.

PMID- 23114697
TI  - Antibody responses to vaccination among South African HIV-exposed and unexposed
      uninfected infants during the first 2 years of life.
AB  - HIV-exposed but uninfected (HEU) infants born to HIV-infected mothers from areas
      in the world with a high burden of infectious disease suffer higher infectious
      morbidity and mortality than their HIV unexposed uninfected (HUU) peers.
      Vaccination provides protection from infection. The possibility exists that
      altered response to vaccination contributes to the higher rate of infection in
      HEU than in HUU infants. While short-term, cross-sectional studies support this
      notion, it is unclear whether or not HEU infants develop long-term protective
      immune responses following the WHO extended program on immunization (EPI).
      Vaccine-specific antibody responses were compared between HEU and HUU infants
      from 2 weeks until 2 years of age in a longitudinal South African cohort. Total
      IgG and antibodies specific for Bordetella pertussis, Haemophilus influenzae type
      b (Hib), tetanus toxoid, hepatitis B virus (HepB), and measles virus were
      measured at multiple time points throughout the first 2 years of life. Prevaccine
      antibodies (maternal antibodies passively acquired) specific for tetanus were
      lower in HEU than in HUU infants, while prevaccine antibodies to HepB were higher
      in HEU than in HUU infants. Both groups responded similarly to tetanus, Hib, and
      HepB vaccination. HEU demonstrated stronger pertussis vaccine responses,
      developing protective titers 1 year earlier than HUU patients, and maintained
      higher anti-tetanus titers at 24 months of age. Vaccine-induced antibodies to
      measles virus were similar in both groups at all time points. Our results suggest
      that the current EPI vaccination program as practiced in South Africa leads to
      the development of vaccine-specific antibody responses that are equivalent in HEU
      and HUU infants. However, our data also suggest that a large fraction of both HEU
      and HUU South African infants have antibody titers for several infectious threats
      that remain below the level of protection for much of their first 2 years of
      life.

PMID- 23114698
TI  - Rational design of membrane proximal external region lipopeptides containing
      chemical modifications for HIV-1 vaccination.
AB  - The inability to generate broadly neutralizing antibody (bnAb) responses to the
      membrane proximal external region (MPER) of HIV-1 gp41 using current vaccine
      strategies has hampered efforts to prevent the spread of HIV. To address this
      challenge, we investigated a novel hypothesis to help improve the anti-MPER
      antibody response. Guided by structural insights and the unique lipid reactivity
      of anti-MPER bnAbs, we considered whether amino acid side chain modifications
      that emulate hydrophilic phospholipid head groups could contribute to the
      generation of 2F5-like or 4E10-like neutralizing anti-MPER antibodies. To test
      this hypothesis, we generated a series of chemically modified MPER immunogens
      through derivatization of amino acid side chains with phosphate or nitrate
      groups. We evaluated the binding affinity of the chemically modified peptides to
      their cognate monoclonal antibodies, 2F5 and 4E10, using surface plasmon
      resonance. The modifications had little effect on binding to the antibodies and
      did not influence epitope secondary structure when presented in liposomes. We
      selected five of the chemically modified sequences to immunize rabbits and found
      that an immunogen containing both the 2F5 and 4E10 epitopes and a phosphorylated
      threonine at T676 elicited the highest anti-peptide IgG titers, although the high
      antipeptide titers did not confer higher neutralizing activity. These data
      indicate that side chain modifications adjacent to known neutralizing antibody
      epitopes are capable of eliciting antibody responses to the MPER but that these
      chemically modified gp41 epitopes do not induce neutralizing antibodies.

PMID- 23114699
TI  - Additional diagnostic yield of adding serology to PCR in diagnosing viral acute
      respiratory infections in Kenyan patients 5 years of age and older.
AB  - The role of serology in the setting of PCR-based diagnosis of acute respiratory
      infections (ARIs) is unclear. We found that acute- and convalescent-phase paired
      sample serologic testing increased the diagnostic yield of naso/oropharyngeal
      swabs for influenza virus, respiratory syncytial virus (RSV), human
      metapneumovirus, adenovirus, and parainfluenza viruses beyond PCR by 0.4% to
      10.7%. Although still limited for clinical use, serology, along with PCR, can
      maximize etiologic diagnosis in epidemiologic studies.

PMID- 23114700
TI  - Detection of Francisella tularensis-specific antibodies in patients with
      tularemia by a novel competitive enzyme-linked immunosorbent assay.
AB  - A novel competitive enzyme-linked immunosorbent assay (cELISA) was developed and
      evaluated for detection of antibodies against Francisella tularensis in humans.
      The assay is based on the ability of serum antibodies to inhibit the binding of
      monoclonal antibodies (MAbs) directed against F. tularensis lipopolysaccharide
      antigens. The assay was evaluated using serum samples of tularemia patients,
      inactivated F. tularensis-immunized rabbits, and F. tularensis-infected mice.
      Antibodies against F. tularensis were successfully detected in serum samples of
      tularemia patients as well as the immunized and infected animals. The cELISA
      method was compared to indirect ELISA (iELISA) and the commonly used
      microagglutination test (MA) using serum samples of 19 tularemia patients and 50
      healthy individuals. The sensitivity and specificity of cELISA were 93.9 and
      96.1%, respectively, in comparison to the iELISA. MA was less sensitive than
      cELISA with a sensitivity and specificity of only 81.8 and 98.0%, respectively. A
      high degree of correlation (R(2) = 0.8226) was observed between cELISA and iELISA
      results. The novel cELISA developed in this study appears to be highly sensitive
      and specific for serodiagnosis of human tularemia. The potential of the MAb-based
      cELISA to be used in both human and animal samples emphasizes its usefulness for
      serological survey of tularemia among multiple animal species.

PMID- 23114701
TI  - Study of avidity of antigen-specific antibody as a means of understanding
      development of long-term immunological memory after Vibrio cholerae O1 infection.
AB  - The avidity of antibodies to specific antigens and the relationship of avidity to
      memory B cell responses to these antigens have not been studied in patients with
      cholera or those receiving oral cholera vaccines. We measured the avidity of
      antibodies to cholera toxin B subunit (CTB) and Vibrio cholerae O1
      lipopolysaccharide (LPS) in Bangladeshi adult cholera patients (n = 30), as well
      as vaccinees (n = 30) after administration of two doses of a killed oral cholera
      vaccine. We assessed antibody and memory B cell responses at the acute stage in
      patients or prior to vaccination in vaccinees and then in follow-up over a year.
      Both patients and vaccinees mounted CTB-specific IgG and IgA antibodies of high
      avidity. Patients showed longer persistence of these antibodies than vaccinees,
      with persistence lasting in patients up to day 270 to 360. The avidity of LPS
      specific IgG and IgA antibodies in patients remained elevated up to 180 days of
      follow-up. Vaccinees mounted highly avid LPS-specific antibodies at day 17 (3
      days after the second dose of vaccine), but the avidity waned rapidly to baseline
      by 30 days. We examined the correlation between antigen-specific memory B cell
      responses and avidity indices for both antigens. We found that numbers of CTB-
      and LPS-specific memory B cells significantly correlated with the avidity indices
      of the corresponding antibodies (P < 0.05; Spearman's rho = 0.28 to 0.45). These
      findings suggest that antibody avidity after infection and immunization is a good
      correlate of the development and maintenance of memory B cell responses to Vibrio
      cholerae O1 antigens.

PMID- 23114702
TI  - Sublethal staphylococcal enterotoxin B challenge model in pigs to evaluate
      protection following immunization with a soybean-derived vaccine.
AB  - In an effort to develop a sustainable platform for manufacturing protein-based
      vaccine candidates, we expressed a triple mutant of staphylococcal enterotoxin B
      carrying the L45R, Y89A, and Y94A modifications in transgenic soybean seeds (soy
      mSEB). Soy-mSEB possessed no detectable superantigen activity in vitro. We found
      that this soybean-derived, nontoxic mutant of SEB could be stably expressed,
      stored in seeds for extended periods at room temperature without degradation, and
      easily purified from contaminating soy proteins. Vaccination of pigs with
      purified soy-mSEB, or the identical triple mutant expressed in Escherichia coli
      (E. coli-mSEB), resulted in high antibody titers against the native toxin in
      immunized animals. In fact, titers were indistinguishable regardless of the
      immunogen used, demonstrating the equivalence of soy-mSEB and E. coli-mSEB
      vaccinations. Antisera from either immunized group were able to block native SEB
      superantigen activity in an in vitro neutralization assay. Similar results were
      obtained when immunized animals were challenged with a sublethal dose of native
      toxin. Significant reductions in toxin-induced serum cytokine levels were
      observed in soy-mSEB- and E. coli-mSEB-immunized pigs compared to control
      animals. The reductions in SEB-induced cytokine responses were similar regardless
      of the immunogen used for vaccination. Surprisingly, however, some clinical
      symptoms, such as prostration, lethargy, emesis, and/or diarrhea, were still
      observed in all immunized animals. These studies demonstrate the potential for
      soybean-derived proteins as a platform technology for sustainable vaccine
      manufacturing and the usefulness of a sublethal challenge model in pigs for
      evaluating the efficacy of potential SEB vaccine candidates.

PMID- 23114703
TI  - Large-scale evaluation of the immuno-mycologics lateral flow and enzyme-linked
      immunoassays for detection of cryptococcal antigen in serum and cerebrospinal
      fluid.
AB  - Cryptococcosis is a systemic infection caused by the pathogenic yeasts
      Cryptococcus neoformans and C. gattii. Detection of cryptococcal capsular antigen
      (CrAg) in serum and cerebrospinal fluid (CSF) plays an important diagnostic role.
      We prospectively compared the new Immuno-Mycologics Inc. (IMMY) lateral flow
      assay (LFA) and enzyme immunoassay (EIA) to our current CrAg test (Premier EIA;
      Meridian Bioscience Inc.). Discordant samples were retested with the latex
      Cryptococcus antigen test (IMMY) and using serotype-specific monoclonal
      antibodies (MAbs). A total of 589 serum and 411 CSF specimens were tested in
      parallel. Qualitative agreement across assays was 97.7%. In all, 56 (41 serum and
      15 CSF) samples were positive and 921 (527 serum and 394 CSF) samples were
      negative by all three assays. The 23 discrepant specimens were all Meridian EIA
      negative. Of 23 discordant specimens, 20 (87.0%) were positive by both the IMMY
      LFA and EIA, 2 were LFA positive only, and 1 was EIA positive only. Eleven
      discrepant specimens had adequate volume for latex agglutination (LA) testing; 8
      were LA positive, and 3 were LA negative. LA-negative samples (2 CSF samples and
      1 serum) had low IMMY LFA/EIA titers (<=1:10). Serotype-specific MAb analysis of
      the LA-positive samples suggested that these specimens contained CrAg epitopes
      similar to those of serotype C strains. In conclusion, the IMMY assays showed
      excellent overall concordance with the Meridian EIA. Assay performance
      differences were related to issues of analytic sensitivity and possible serotype
      bias. Incomplete access to patient-level data combined with low specimen volumes
      limited our ability to fully resolve discrepant results.

PMID- 23114704
TI  - Serologic evidence of pandemic influenza virus H1N1 2009 infection in cats in
      China.
AB  - Infection of domestic cats with (H1N1) pandemic 2009 (pdm09) influenza A virus
      has recently been documented. In this paper, we report for the first time the
      sporadically current seroprevalence of (H1N1) pdm09 influenza A virus infection
      in cats in China. Thirteen of 1,080 sera were found positive by nucleoprotein
      (NP)-specific enzyme-linked immunosorbent assays (ELISAs) in different cat
      populations in southern China. It is very important to stress further
      surveillance of pandemic (H1N1) 2009 influenza A virus in cats in southern China.

PMID- 23114705
TI  - Immunization of mice with formalin-inactivated spores from avirulent Bacillus
      cereus strains provides significant protection from challenge with Bacillus
      anthracis Ames.
AB  - Bacillus anthracis spores are the infectious form of the organism for humans and
      animals. However, the approved human vaccine in the United States is derived from
      a vegetative culture filtrate of a toxigenic, nonencapsulated B. anthracis strain
      that primarily contains protective antigen (PA). Immunization of mice with
      purified spore proteins and formalin-inactivated spores (FIS) from a
      nonencapsulated, nontoxigenic B. anthracis strain confers protection against B.
      anthracis challenge when PA is also administered. To investigate the capacity of
      the spore particle to act as a vaccine without PA, we immunized mice
      subcutaneously with FIS from nontoxigenic, nonencapsulated B. cereus strain G9241
      pBCXO1(-)/pBC210(-) (dcG9241), dcG9241 DeltabclA, or 569-UM20 or with exosporium
      isolated from dcG9241. FIS vaccination provided significant protection of mice
      from intraperitoneal or intranasal challenge with spores of the virulent B.
      anthracis Ames or Ames DeltabclA strain. Immunization with dcG9241 DeltabclA FIS,
      which are devoid of the immunodominant spore protein BclA, provided greater
      protection from challenge with either Ames strain than did immunization with FIS
      from BclA-producing strains. In addition, we used prechallenge immune antisera to
      probe a panel of recombinant B. anthracis Sterne spore proteins to identify novel
      immunogenic vaccine candidates. The antisera were variably reactive with BclA and
      with 10 other proteins, four of which were previously tested as vaccine
      candidates. Overall our data show that immunization with FIS from nontoxigenic,
      nonencapsulated B. cereus strains provides moderate to high levels of protection
      of mice from B. anthracis Ames challenge and that neither PA nor BclA is required
      for this protection.

PMID- 23114706
TI  - Ab initio based multiscale modeling of alloy surface segregation.
AB  - A fully integrated ab initio based multiscale model for analysis  of segregation
      at alloy surfaces is presented. Major components of the model include a structure
      energy analysis from the first-principles density functional theory (DFT), a
      Monte Carlo/molecular dynamics (MC/MD) hybrid simulation scheme for atomic
      transport, and a reactive force field formalism that binds the two. The
      multiscale model accurately describes the atomic transport processes in a multi
      component alloy system at finite temperature, and is capable of providing
      quantitative predictions for surface compositions. The validity of the model was
      demonstrated by investigating the temperature-dependent segregation behavior of
      B2 FeAl binary alloy surfaces with a detailed description of the segregation
      mechanism. Based on the model's prediction capabilities, potential extension of
      the model to the analysis of systems undergoing rapid chemical reactions is
      discussed.

PMID- 23114707
TI  - A concise synthesis of 3-aroylflavones via Lewis base 9-azajulolidine-catalyzed
      tandem acyl transfer-cyclization.
AB  - Lewis base-catalyzed tandem acyl transfer-cyclization of acylated o
      alkynoylphenols leading to 3-aroylflavones was developed. 9-Azajulolidine
      smoothly promoted the reaction of the aroyl derivatives at ambient temperature,
      and the structure-diversed synthesis of 3-aroylflavones with distinct
      substituents was achieved in moderate to excellent yields.

PMID- 23114708
TI  - The cytologic composition of dacryops: an immunohistochemical investigation of 15
      lesions compared to the normal lacrimal gland.
AB  - PURPOSE: To define the cytologic composition of the double-layered epithelial
      lining of dacryops (lacrimal duct cyst), improve histopathologic diagnosis, and
      better understand pathogenesis. DESIGN: Clinicopathologic retrospective study
      with immunohistochemical studies of 15 lesions compared with normal lacrimal
      gland. METHODS: Clinical data from 14 patients were reviewed and microscopy was
      performed with routine stains and immunohistochemical probes for epithelial
      membrane antigen (EMA), gross cystic disease fluid protein-15 (GCDFP-15),
      cytokeratin 7 (CK7), and smooth muscle actin (SMA). RESULTS: The major lacrimal
      gland was involved in 13 lesions; 2 lesions arose in an accessory gland of
      Krause. One case was bilateral; the average age of the patients was 50.7 years.
      Neither visual acuity nor motility was disturbed. No lesion was discovered to
      have recurred after excision. Microscopically, in all dacryops specimens goblet
      cells and luminal pseudoapocrine apical cytoplasmic projections were identified.
      Lacrimal acinar cells immunoreacted with GCDFP-15 and CK7, whereas the normal
      ducts and the epithelium of the dacryops lesions reacted diffusely only with CK7.
      SMA-positive myoepithelial cells were found in the acini but not in the normal
      ducts or dacryops epithelium. CONCLUSIONS: Negative GCDFP-15 staining ruled out
      apocrine metaplasia in dacryops. Normal ducts and dacryops showed no
      immunohistochemical evidence for the presence of myoepithelial cells.
      Pathogenetic theories of dacryops that implicate a failure of ductular
      "neuromuscular" contractility must therefore be revised. A dysfunction of the
      rich neural plexus around the ductules may play a role in the development of
      dacryops in conjunction with periductular inflammation and induced scarring.

PMID- 23114709
TI  - [Imaging of patellofemoral instability].
AB  - Patellofemoral instability remains a diagnostic and therapeutic challenge due to
      its multifactorial genesis. The purpose of imaging is to systematically analyze
      predisposing factors, such as trochlear dysplasia, patella alta, tibial
      tuberosity-trochlear groove (TT-TG) distance, rotational deformities of the lower
      limb and patellar tilt. In order to evaluate anatomical abnormalities with a
      sufficient diagnostic accuracy, standardized measurement methods and
      implementation of various imaging modalities are necessary.Diagnosis of acute and
      often overlooked lateral patellar dislocation can be established with magnetic
      resonance imaging (MRI) because of its characteristic patterns of injury. Damage
      to the medial patellofemoral ligament (MPFL) has a significance just as high as
      the predisposing risk factors in relation to the cause of chronic instability.

PMID- 23114710
TI  - [Acute appendicitis: a clinical diagnosis?].

PMID- 23114711
TI  - Treatment-induced secretion of WNT16B promotes tumor growth and acquired
      resistance to chemotherapy: implications for potential use of inhibitors in
      cancer treatment.
AB  - Innate or acquired resistance to chemotherapy presents an important and
      predictable challenge in cancer therapy. Malignant tumors consist of both
      neoplastic and benign cells such as stromal fibroblasts, which can influence the
      tumor's response to cytotoxic therapy. In a recent article in Nature Medicine,
      Sun et al. show that increased expression of Wnt family member wingless-type MMTV
      integration site family member 16B (WNT16B) by the tumor microenvironment in
      response to cytotoxic damage and signals through the canonical Wnt pathway to
      promote tumor growth and chemotherapy resistance. Such findings outline a
      mechanism by which cytotoxic therapies given in cyclical doses can actually
      augment later treatment resistance and may open the door to new areas of research
      and to the development of new therapeutic targets that block the DNA damage
      response program.

PMID- 23114712
TI  - Adult primary pulmonary primitive neuroectodermal tumor: molecular features and
      translational opportunities.
AB  - Primitive neuroectodermal tumors (PNET) arising directly from the lung are very
      rare but particularly aggressive neoplasms. We report a case of a 31-y-old man
      with primary pulmonary neuroectodermal tumor. We review the clinical as well as
      pathological features. As typical for these tumors, the diagnosis was initially
      delayed in our patient and prognosis was poor despite aggressive surgical
      resection, postoperative chemotherapy and local irradiation. Recent biological
      insights have revealed unique chromosomal translocations crucial to the
      pathogenesis of these tumors, most notably the EWS-FLI-1 translocation. We
      provide an overview of the molecular features of the Ewing Sarcoma Family of
      Tumors (ESFT) including PNET and their potential implications for therapeutic
      targeting.

PMID- 23114713
TI  - Inhibition of the MUC1-C oncoprotein is synergistic with cytotoxic agents in the
      treatment of breast cancer cells.
AB  - Mucin 1 (MUC1) is a heterodimeric glycoprotein that is aberrantly overexpressed
      in most human breast cancers. The oncogenic MUC1-C subunit promotes survival and
      blocks the apoptotic response to genotoxic anticancer agents. In the present
      studies, human MCF-7 and ZR-75-1 breast cancer cells were treated with the MUC1-C
      inhibitor, GO-203, a cell-penetrating peptide that blocks MUC1-C homodimerization
      and thereby its oncogenic function. Treatment with GO-203 was found to promote
      the apoptotic response of MCF-7 and ZR-75-1 cells to the therapeutic drugs taxol
      and doxorubicin (DOX). This effect was (1) attenuated by a pan-caspase inhibitor,
      and (2) mediated, at least in part, by activation of the effector caspase-7 and
      cleavage of the downstream substrate PARP. Further analysis of the interaction
      between GO-203 and taxol using isobolograms, which evaluate the nature of the
      interaction of two drugs, demonstrated that the combination is highly
      synergistic. These results were supported by combination index (CI) analysis with
      values of less than 1. GO-203 was also highly synergistic with DOX in studies of
      both MCF-7 and ZR-75-1 breast cancer cells. These findings indicate that blocking
      MUC1-C function could be effective in combination with taxol and DOX for the
      treatment of breast cancer.

PMID- 23114714
TI  - Serum caveolin-1, a biomarker of drug response and therapeutic target in prostate
      cancer models.
AB  - We investigated the effect of dasatinib and sunitinib on tyrosine kinase (TK)
      signaling, caveolin-1 (Cav-1) expression and secretion and proliferation of PC-3
      and DU145 prostate cancer cells in vitro and in vivo. Treatment of both cell
      lines with either dasatinib or sunitinib reduced phosphorylation of PDGFR,
      VEGFR2, Akt, FAK, Src (dasatinib only) and Cav-1, and reduced cellular and
      secreted levels of Cav-1. Both agents dose-dependently inhibited proliferation of
      these cells. In PC-3 and DU145 subcutaneous xenografts, treatment with dasatinib,
      sunitinib or anti-Cav-1 antibody (Ab) alone produced significant tumor regression
      compared with that by vehicle or IgG alone. Combined dasatinib and anti-Cav-1 Ab
      treatment or sunitinib and anti-Cav-1 Ab produced greater tumor regression than
      either treatment alone. Serum Cav-1 levels were lower in dasatinib- and sunitinib
      treated mice than they were in vehicle-treated mice, and correlated positively
      with tumor growth in dasatinib- and sunitinib-treated groups (r = 0.48, p =
      0.031; r = 0.554, p = 0.0065, respectively), compared with vehicle controls. Cav
      1 knockdown, in combination with dasatinib or sunitinib treatment in PC-3 cells,
      caused a greater reduction in the phosphorylation of PDGFR-beta and VEGFR2, and
      expression and secretion of PDGF-B and VEGF-A than that in PC-3 cells treated
      with dasatinib or sunitinib alone in control siRNA cells, suggesting that Cav-1
      is involved in an autocrine pathway that is affected by these drugs. Overall, our
      results suggest a role for Cav-1 as a biomarker of response to both dasatinib and
      sunitinib treatment and as a therapeutic target in prostate cancer.

PMID- 23114716
TI  - Write your own journey in 2013.

PMID- 23114715
TI  - Tumor regression by phenethyl isothiocyanate involves DDB2.
AB  - Phenethyl isothiocyanate (PEITC) is a promising cancer chemopreventive agent
      commonly found in edible cruciferous vegetables. It has been implicated also for
      therapy, and is in clinical trial for lung cancer. Here, we provide evidence that
      the tumor suppressive effect of PEITC is related to its ability to induce
      expression of damaged DNA binding protein 2 (DDB2), a DNA repair protein involved
      also in apoptosis and premature senescence. DDB2 expression is attenuated in a
      wide variety of cancers including the aggressive colon cancers. We show that, in
      colon cancer cells, reactive oxygen species, which are induced by PEITC, augment
      expression of DDB2 through the p38MAPK/JNK pathway, independently of p53. PEITC
      induced expression of DDB2 is critical for inhibition of tumor progression by
      PEITC. Tumors derived from DDB2-deficient colon cancer cells are refractory to
      PEITC-treatments, resulting from deficiencies in apoptosis and senescence. The
      DDB2-proficient tumors, on the other hand, respond effectively to PEITC. The
      results show that PEITC can be used to induce expression of DDB2, and that
      expression of DDB2 is critical for effective response of tumors to PEITC.

PMID- 23114717
TI  - Crohn disease: recognition is key.
AB  - Crohn disease (CD) is an autoimmune disease that affects people across the
      lifespan. Patients with CD are predisposed to other autoimmune illnesses, such as
      psoriasis or arthritis, and suffer from complications including infection and
      malnutrition. This article will focus on the diagnosis and treatment of CD.

PMID- 23114718
TI  - Sinus node dysfunction: recognition and treatment.
AB  - Sinus node dysfunction (SND) refers to a wide range of abnormalities involving
      sinus node and atrial impulse generation and propagation. SND occurs at any age
      and is commonly encountered in clinical practice. Clinicians must be able to
      accurately diagnose this syndrome, which can present from asymptomatic
      bradycardia to atrial standstill.

PMID- 23114719
TI  - Molecular cloning and polymorphism of the major histocompatibility complex (MHC)
      class IIB gene of grass carp (Ctenopharyngodon idella).

PMID- 23114720
TI  - Influence of adiponectin and resistin gene polymorphisms on quantitative traits
      related to metabolic syndrome among Malay, Chinese, and Indian men in Malaysia.

PMID- 23114721
TI  - SOD1 gene transfer into paraventricular nucleus attenuates hypertension and
      sympathetic activity in spontaneously hypertensive rats.
AB  - Excessive sympathetic activity contributes to the initiation and progression of
      hypertension. Reactive oxygen species in the paraventricular nucleus (PVN) is
      involved in sympathetic overdrive and hypertension. The present study was
      designed to investigate whether superoxide dismutase 1 (SOD1) overexpression in
      the PVN attenuated sympathetic activation and hypertension. Adenoviral vectors
      containing human SOD1 or null adenoviral vectors were microinjected into the PVN
      of Wistar rats and spontaneously hypertensive rats (SHR). Significant depressor
      effects were observed from weeks 1 to 4 after SOD1 gene transfer in SHR. Acute
      experiments were carried out at the end of the 3rd week. In the PVN, superoxide
      anion and angiotensin II levels were increased while SOD1 activity and protein
      expression were decreased in SHR, which were attenuated by SOD1 overexpression in
      the PVN. However, SOD1 overexpression had no significant effect on the SOD2
      activity in the PVN. The blood pressure response to ganglionic blockade, cardiac
      sympathetic nerve activity, and cardiac sympathetic afferent reflex (CSAR) were
      enhanced, and the plasma norepinephrine level was increased in SHR, which were
      prevented by SOD1 gene transfer in the PVN. Furthermore, SOD1 overexpression
      decreased the ratio of left ventricular weight to body weight, cross-sectional
      areas of myocardial cells, media thickness, and the media/lumen ratio of small
      arteries in the heart in SHR. These results indicate that SOD1 overexpression in
      the PVN reduces arterial blood pressure, attenuates excessive sympathetic
      activity and CSAR, and improves myocardial and vascular remodeling in SHR.

PMID- 23114722
TI  - Personal resources and support when regaining the ability to work: an interview
      study with Exhaustion Disorder patients.
AB  - PURPOSE: The aim of the study was to explore experiences and thoughts in the
      process of returning to work in employed patients with Exhaustion Disorder.
      METHODS: Twelve patients with Exhaustion Disorder (burnout) who had been referred
      to a Stress Rehabilitation Clinic were interviewed. All patients were employed
      but a majority was on full or part-time sick leave. Grounded Theory was used as
      the qualitative method. RESULTS: A core category, regaining the ability to work,
      was developed. Alongside, two categories, internal resources and the external
      support system, were experienced as being important to the process. The internal
      resources were expressed through three key features (sub-categories), perceived
      validation, insights and adaptive coping abilities. The external support system
      was diverse and described by the sub-categories practical/structural and/or
      emotional support. Four external support actors were identified; the workplace,
      health care, the Social Insurance Agency, and the union. The supervisor was
      described as the most important external actor. CONCLUSIONS: Internal and
      external resources are intertwined in the process of regaining the ability to
      work. The internal resources and external support can directly increase the
      probability to regain the ability to work. Moreover, these resources can affect
      each other and thus indirectly have an effect on the process.

PMID- 23114723
TI  - Tuning the photophysical properties of cationic iridium(III) complexes containing
      cyclometallated 1-(2,4-difluorophenyl)-1H-pyrazole through functionalized 2,2'
      bipyridine ligands: blue but not blue enough.
AB  - Four new heteroleptic iridium(III) complexes in the family
      [Ir(dfppz)(2)(N^N)](+), where Hdfppz = 1-(2,4-difluorophenyl)-1H-pyrazole and N^N
      = 6-phenyl-2,2'-bipyridine (1), 4,4'-(di-tert-butyl)-6-phenyl-2,2'-bipyridine
      (2), 4,4'-(di-tert-butyl)-6,6'-diphenyl-2,2'-bipyridine (3) and 4,4'
      bis(dimethylamino)-2,2'-bipyridine (4), have been synthesized as the
      hexafluoridophosphate salts and fully characterized. Single crystal structures of
      ligand 3 and the precursor [Ir(2)(dfppz)(4)(MU-Cl)(2)] have been determined,
      along with the structures of the complexes
      4{[Ir(dfppz)(2)(1)][PF(6)]}.3CH(2)Cl(2), [Ir(dfppz)(2)(3)][PF(6)].CH(2)Cl(2) and
      [Ir(dfppz)(2)(4)][PF(6)].CH(2)Cl(2). The role of inter- and intramolecular face
      to-face pi-stacking in the solid state is discussed. In the
      [Ir(dfppz)(2)(N^N)](+) (N^N = 1-3) cations, the phenyl substituent in ligands 1,
      2 or 3 undergoes hindered rotation on the NMR timescale at 298 K in solution and
      the systems have been studied by variable temperature NMR spectroscopy.
      Acetonitrile solutions of [Ir(dfppz)(2)(N^N)][PF(6)] (N^N = 1-3) exhibit similar
      absorption spectra arising from ligand-based transitions; absorption intensity is
      enhanced on going to [Ir(dfppz)(2)(4)][PF(6)] and the spectrum extends further
      into the visible region. Acetonitrile solutions of the complexes are blue
      emitters with lambda(em) = 517, 505, 501 and 493 nm for N^N = 1, 2, 3 and 4,
      respectively (lambda(exc) = 280-310 nm). The redox behaviours of
      [Ir(dfppz)(2)(N^N)][PF(6)] (N^N = 1-3) are similar, and the introduction of the
      electron-donating NMe(2) substituents onto the N^N ligand shifts the metal
      centred oxidation to less positive potentials. Theoretical calculations predict a
      mixed metal-to-ligand/ligand-to-ligand charge transfer (MLCT/LLCT) character for
      the emitting triplet state in agreement with the broad and unstructured character
      of the emission bands. The NMe(2) substituents enlarge the HOMO-LUMO gap and blue
      shifts the emission of [Ir(dfppz)(2)(4)](+) that is centred on the ancillary
      ligand. These complexes, when processed into a thin film and sandwiched between
      two electrodes, lead to very low voltage operating electroluminescent devices. No
      additional components are needed, which demonstrates their electron and hole
      transport abilities in conjunction with the luminescent properties.

PMID- 23114724
TI  - Saponin promotes rapid identification and antimicrobial susceptibility profiling
      of Gram-positive and Gram-negative bacteria in blood cultures with the Vitek 2
      system.
AB  - The rapid identification and antimicrobial susceptibility testing (AST) of
      bacteria in clinical blood cultures is crucial to optimise antimicrobial therapy.
      A previous study involving small sample numbers revealed that the addition of
      saponin to blood cultures, further referred to as the new method, shortened
      considerably the turn-around time for the identification and AST of Gram-positive
      cocci as compared to the current method involving an overnight subculture. Here,
      we extend previous results and compare the identification and AST of blood
      cultures containing Gram-negative bacilli by the new and current methods. The
      identification and AST of 121 Gram-positive and 109 Gram-negative bacteria in
      clinical monomicrobial blood cultures by the new and current methods and, in the
      case of Gram-negative bacilli, by direct (no additions) inoculation into an
      automated system (rapid method) was assessed using the Vitek 2 system.
      Discrepancies between the results obtained with the different methods were solved
      by manual methods. The new method correctly identified 88 % of Gram-positive and
      98 % of Gram-negative bacteria, and the rapid method correctly identified 94 % of
      Gram-negative bacteria. The AST for all antimicrobials by the new method were
      concordant with the current method for 55 % and correct for an additional 9 % of
      Gram-positive bacteria, and concordant with the current method for 62 % and
      correct for an additional 21 % of Gram-negative bacilli. The AST by the rapid
      method was concordant with the current method for 62 % and correct for an
      additional 12 % of Gram-negative bacilli. Together, saponin-treated monomicrobial
      blood cultures allow rapid and reliable identification and AST of Gram-positive
      and Gram-negative bacteria.

PMID- 23114725
TI  - Lack of the QTc physiologic decrease during cardiac stress test in patients with
      type 2 diabetes treated with secretagogues.
AB  - Patients with type 2 diabetes are at increased susceptibility to a prolonged QT
      interval. Furthermore, insulin secretagogues, drugs used to treat diabetes, may
      prolong QT interval and provoke arrhythmias. We evaluated whether secretagogues
      can affect QTc interval during cardiac stress test in 20 patients with type 2
      diabetes treated with secretagogues. ECG stress test was performed in all
      patients. QTc interval was calculated both before cardiac stress test (BCST) and
      at acme of cardiac stress test (ACST). Diabetic patients treated with
      secretagogues showed longer QTc-ACST values than those treated with metformin
      only. QTc-ACST values resulted shorter than QTc-BCST values in control group.
      Diabetic patients treated with secretagogues showed QTc-ACST values significantly
      longer than QTc-BCST values. In our study, diabetic patients treated with
      secretagogues did not show the QTc physiologic decrease that is a protective
      against arrhythmias. These results suggest to evaluate, in these patients, QT
      length, even during routine cardiac stress test. 

PMID- 23114726
TI  - Suppression of 12-O-tetradecanoylphorbol-13-acetate-induced MCF-7 breast
      adenocarcinoma cells invasion/migration by alpha-tomatine through activating
      PKCalpha/ERK/NF-kappaB-dependent MMP-2/MMP-9 expressions.
AB  - alpha-Tomatine, isolated from Lycopersicon esculentum Linn., is a naturally
      occurring glycoalkaloids in immature green tomatoes. Some reports demonstrated
      that alpha-tomatine had various anti-carcinogenic properties. First, the result
      demonstrated alpha-tomatine could inhibit TPA-induced the abilities of the
      adhesion, morphology/actin cytoskeleton arrangement, invasion, and migration by
      cell-matrix adhesion assay, immunofluorescence stain assay, Boyden chamber
      invasion assay, and wound-healing assay. Data also showed alpha-tomatine could
      inhibit the activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2)
      and protein kinase C-alpha (PKCalpha) involved in the downregulation of the
      enzyme activities and messenger RNA levels of matrix metalloproteinase-2/9 (MMP
      2/MMP-9) induced by TPA. Next, alpha-tomatine also strongly inhibited TPA-induced
      the activation of nuclear factor kappa B (NF-kappaB) and phospho-inhibitor of
      kappa Balpha (phospho-IkappaBalpha). In addition, TPA-induced translocation of
      PKC-alpha from cytosol to membranes, and suppression of TPA elicited the
      expression of PKC-alpha by adding the PKC-alpha inhibitors, GF-109203X and Go
      6983. The treatment of specific inhibitor for ERK (U0126) to MCF-7 cells could
      inhibit TPA-induced MMP-2/MMP-9 and phospho-ERK along with an inhibition on cell
      invasion and migration. Application of alpha-tomatine to prevent the
      invasion/migration of MCF-7 cells through blocking PKCalpha/ERK/NF-kappaB
      activation is first demonstrated herein.

PMID- 23114727
TI  - Emerging new biomarkers in obstructive sleep apnea.

PMID- 23114730
TI  - [Junior academy: curricular, adjunct advanced further educational program].

PMID- 23114728
TI  - Assessment of the uvulo-glossopharyngeal dimensions in patients with beta
      thalassemia major.
AB  - OBJECTIVES: Thalassemia patients present varying degrees of craniofacial
      characteristics, while the morphology of the upper airway is less studied. The
      purpose of this study was to compare the uvula-glossopharyngeal dimensions (UGDs)
      of patients with beta-thalassemia major (BTM) with non-thalassemic subjects who
      had similarities in the maxillo-mandibular skeletal pattern. SUBJECTS AND
      METHODS: The material for this cross-sectional retrospective study consisted of
      lateral cephalograms of 40 BTM patients (23 males, 17 females, aged 9.5 +/- 0.97
      years). These were compared with lateral cephalograms of a control group of 40
      non-thalassemic subjects (23 males, 17 females, aged 11.0 +/- 0.87 years). The
      control group was chosen so that they had similarities with the BTM patients in
      the following cephalometric variables: SNA (in degree), SNB (in degree), ANB (in
      degree), and anterior facial height (N-Me). RESULTS: The following UGDs in
      thalassemic subjects were significantly shorter in patients with BTM: tongue
      length (P < 0.05), the distance between the hyoid bone and the mandibular plane
      (P < 0.01), and the vertical distance between hyoid bone and the C3-RGN line
      (line connecting third vertebra and retrognathion) (P < 0.05). The middle airway
      space in BTM patients was significantly wider (P < 0.05), and a trend was
      observed for the wider inferior airway space (P = 0.07). CONCLUSIONS: Based on
      this study, some UGDs in BTM patients were significantly different, compared to
      non-thalassemic subjects who had a similar maxillo-mandibular skeletal pattern.
      These findings may have implications for the long-term treatment of BTM patients;
      however, since groups were not exactly age-matched, the observed differences
      between groups could be attributed to either BTM, age, or both. Additional
      studies with age-matched subjects are needed to investigate the relationship
      between BTM and UGDs.

PMID- 23114729
TI  - The organ specificity in pathological damage of chronic intermittent hypoxia: an
      experimental study on rat with high-fat diet.
AB  - PURPOSE: It is known today that sleep apnea hypopnea syndrome and its
      characteristic chronic intermittent hypoxia can cause damages to multiple organs,
      including the cardiovascular system, urinary system, and liver. It is still
      unclear, however, whether the damage caused by sleep apnea hypopnea syndrome and
      the severity of the damage are organ-specific. METHODS: This research observed
      the pathological effects of chronic intermittent hypoxia on rat's thoracic aorta,
      myocardium, liver, and kidney, under the condition of lipid metabolism
      disturbance, through establishing the rat model of chronic intermittent hypoxia
      with high-fat diet by imitating the features of human sleep apnea hypopnea
      syndrome. In this model, 24 male Wistar rats were randomly divided into three
      groups: a control group fed by regular diet, a high-fat group fed by high-fat
      diet, and a high-fat plus intermittent hypoxia group fed by high-fat diet and
      treated with intermittent hypoxia 7 h a day. At the end of the ninth week, the
      pathological changes of rat's organs, including the thoracic aorta, myocardium,
      liver, and kidney are observed (under both optical microscopy and transmission
      electron microscopy). RESULTS: As the result of the experiment shows, while there
      was no abnormal effect observed on any organs of the control group, slight
      pathological changes were found in the organs of the high-fat group. For the high
      fat plus intermittent hypoxia group, however, remarkably severer damages were
      found on all the organs. It also showed that the severity of the damage varies by
      organ in the high-fat plus intermittent hypoxia group, with the thoracic aorta
      being the worst, followed by the liver and myocardium, and the kidney being the
      slightest. CONCLUSIONS: Chronic intermittent hypoxia can lead to multiple-organ
      damage to rat with high-fat diet. Different organs appear to have different
      sensitivity to chronic intermittent hypoxia.

PMID- 23114731
TI  - Modeling of superheating and undercooling of strained semiconductor nanocrystals
      in SiO2.
AB  - Although superheating and undercooling of nanocrystals have been observed and
      simply modeled, physical aspects of the nanocrystals, like strain, have
      previously been ignored. In this article the size dependence of the melting and
      solidification point temperature of semiconductor nanocrystals embedded in an
      interface epitaxy free matrix is modeled, taking into account the strain state of
      the nanocrystals. A configurational entropy term is introduced to render the
      model applicable to any crystal size, including bulk. The model is validated on
      the system of InSb nanocrystals embedded in SiO(2) under a high compressive
      strain.

PMID- 23114732
TI  - Eating patterns and composition of meals and snacks in elite Canadian athletes.
AB  - The purpose of this study was to determine the meal- and snack-eating frequency
      and the nutritional composition of each eating occasion of Canadian high
      performance athletes during training. Athletes from 8 Canadian Sport Centres
      prospectively completed 3-d dietary records including all food, fluid, and
      supplements consumed. The time of consumption and whether the consumption was a
      meal or snack were also identified. The dietary records were analyzed for energy
      (kcal) and macronutrient intake (carbohydrate, protein, and fat) and compared
      based on gender, age, meal vs. snack, and training vs. rest days. Three hundred
      twenty-four athletic subjects (64% female and 36% male) completed the study. On
      average, the athletes ate 4.8 +/- 0.8 times daily. Nearly all athletes consumed 3
      daily meals of breakfast (98.9%), lunch (97.9%), and dinner (98.7%), with few
      having snacks: 57%, 71.6%, and 58.1% of athletes consumed an a.m., p.m., and
      evening snack, respectively. Training-day meal frequency did not differ from that
      during rest days; however, fewer snacks were consumed on rest days. A.m. and p.m.
      snacks were consumed significantly more often on training days than rest days.
      Overall, snacks contributed 24.3% of total daily energy intake. Few dietary
      variations were discovered between genders, while the youngest athletes (<18 yr)
      ate less often, especially their morning snack, than the older athletes. In
      conclusion, Canadian high-performance athletes self-adjusted their energy intakes
      on training vs. rest days primarily by snacking less and reducing their
      carbohydrate and protein intakes on rest days, yet they consistently ate regular
      meals.

PMID- 23114733
TI  - Enzyme-based D-flip-flop memory system.
AB  - The enzyme system was used to mimic the D-flip-flop memory unit. The reversible
      conversion of NAD(+) and NADH cofactors was used to encode the states of the
      memory unit, while a mixture of inhibitors was used as the Clock input and the
      substrates were used as the Data input.

PMID- 23114735
TI  - Emergency contraception -- mechanisms of action.
AB  - Concerns regarding the mechanisms of action of emergency contraception (EC)
      create major barriers to widespread use and could also lead to incorrect use of
      EC and overestimation of its effectiveness. While the copper intrauterine device
      (Cu-IUD) is the most effective method available for EC, the hormonal methods are
      frequently considered to be more convenient and acceptable. Today, the most
      commonly used method for hormonal EC is levonorgestrel (LNG). More recently, the
      progesterone receptor modulator ulipristal acetate (UPA) has been shown to be
      more effective than LNG to prevent an unwanted pregnancy. The main mechanism of
      action of both LNG and UPA for EC is delaying or inhibiting ovulation. However,
      UPA appears to have a direct inhibitory effect on follicular rupture which allows
      it to be effective even when administered shortly before ovulation, a time period
      when use of LNG is no longer effective. The main mechanism of action of the Cu
      IUD is to prevent fertilization through the effect of Cu ions on sperm function.
      In addition, if fertilization has already occurred, Cu ions influence the female
      reproductive tract and prevent endometrial receptivity. Based on this review of
      the published literature, it can be concluded that existing methods used today
      for EC act mainly through inhibition of ovulation or prevention of fertilization.
      An additional effect on the endometrium as occurs for the Cu-IUD, but not for the
      hormonal alternatives, seems to increase the efficacy of the method.

PMID- 23114736
TI  - The effect of follow-up visits or contacts after contraceptive initiation on
      method continuation and correct use.
AB  - BACKGROUND: We conducted a systematic review to assess whether follow-up visits
      or contacts after a woman begins using contraception improve method continuation
      and correct use. STUDY DESIGN: We searched the PubMed database for all peer
      reviewed articles in any language published from database inception through May
      2012 that examined the effect of a structured follow-up schedule of visits or
      contacts on contraceptive use. We included studies that compared women who
      initiated a method of contraception with a certain follow-up schedule compared to
      women with a different follow-up schedule or no follow-up at all. To be included,
      studies must have compared groups on a measure of contraceptive use (e.g.,
      pregnancy, correct use, consistent use, method discontinuation including
      expulsion). Though not ideally suited to answer our review question, studies in
      which women used a variety of contraceptive methods but results were not
      stratified by method type were included. RESULTS: Four studies met our inclusion
      criteria (Level I, poor to II-2, poor). Two studies examined the effect of a
      specific follow-up visit schedule on intrauterine device (IUD) continuation: one
      examining frequency of visits and one examining the timing of the first follow-up
      visit. Women with more frequent follow-up visits did not have a statistically
      significant difference in proportion of removals for medical reasons compared
      with women who had fewer follow-up visits; among women who had their IUDs removed
      for medical reasons, those who had more frequent follow-up visits had a longer
      mean time of use prior to removal. The other study found more removals and
      shorter continuation among women with a follow-up visit at 1 week compared to
      women with a follow-up visit at 1 month after IUD insertion (no statistical tests
      reported). Two studies examined the effect of follow-up phone calls compared to
      no follow-up phone calls after an initial family planning visit among adolescents
      initiating a variety of contraceptive methods. Neither of the two studies found
      any differences in method continuation or correct use between study groups.
      CONCLUSIONS: It is difficult to determine what effect, if any, follow-up visits
      or contacts have on contraceptive method continuation or correct use. Few studies
      were identified, and those that were identified were mostly of poor quality, were
      not method specific and had either poor patient compliance with follow-up visits
      or poor phone contact completion rates.

PMID- 23114738
TI  - Azelastine/fluticasone propionate(Dymista) for seasonal allergic rhinitis.

PMID- 23114737
TI  - Feasibility of LNG-IUS in a baboon model.
AB  - BACKGROUND: The baboon (Papio hamadryas anubis) is an attractive model for
      intrauterine contraception research due to anatomic similarity to the human.
      Although non-human primates have previously been used for intrauterine
      contraception research, it was unknown whether modern intrauterine devices (IUDs)
      can be placed in an anatomically similar position in the baboon. This study
      sought to determine whether human-use IUDs could be seated correctly in the
      uterus of the baboon. STUDY DESIGN: The levonorgestrel-releasing intrauterine
      system (LNG-IUS) was placed ex vivo into two baboon uteri collected at necropsy
      and in three living, reproductively proven baboons. RESULTS: Correct placement of
      human-use IUDs in the baboon was confirmed by both MRI and ultrasound. This study
      establishes that a LNG-IUS can be inserted into the baboon uterus and maintained
      without clinically adverse effects for at least 6 months. The positioning of the
      device is similar to positioning found in women. CONCLUSION: These findings
      provide important support for studying IUD safety and efficacy in the baboon.

PMID- 23114739
TI  - Pneumococcal vaccine for adults.

PMID- 23114740
TI  - In brief: Budeprion XL has been withdrawn.

PMID- 23114741
TI  - Endoscopic ultrasound-guided versus conventional transmural techniques have
      comparable treatment outcomes in draining pancreatic pseudocysts.
AB  - We carried out the first meta-analysis comparing the technical success and
      clinical outcomes of endoscopic ultrasound-guided drainage (EUD) and conventional
      transmural drainage (CTD) for pancreatic pseudocysts. We searched PubMed, Embase,
      Scopus, and the Cochrane library to identify relevant prospective trials. The
      technical success rate, short-term (4-6 weeks) success, and long-term (at 6
      months) success in symptoms and the radiologic resolution of pseudocysts,
      complication rates, and death rates were compared. Two eligible randomized
      controlled trials and two prospective studies including 229 patients were
      retrieved. The technical success rate was significantly higher for EUD than for
      CTD [risk ratio (RR)=12.38, 95% confidence interval (CI): 1.39-110.22]. When CTD
      failed because of the nonbulging nature of pseudocysts, a crossover was carried
      out to EUD (n=18), which was successfully performed in all these cases. All
      patients with portal hypertension and bleeding tendency were subjected to EUD to
      avoid severe complications. EUD was not superior to CTD in terms of short-term
      success (RR=1.03, 95% CI: 0.95-1.11) or long-term success (RR=0.98, 95% CI: 0.76
      1.25). The overall complications were similar in both groups (RR=0.98, 95% CI:
      0.52-1.86). The most common complications were bleeding and infection. There were
      two deaths from bleeding after CTD. The short-term and long-term treatment
      success of both methods is comparable only if proper drainage modality is
      selected in specific clinical situations. For bulging pseudocysts, either EUD or
      CTD can be selected whereas EUD is the treatment of choice for nonbulging
      pseudocysts, portal hypertension, or coagulopathy.

PMID- 23114742
TI  - Splanchnic vein thrombosis and variceal rebleeding in patients with cirrhosis.
AB  - OBJECTIVES: Splanchnic vein thrombosis (SVT) affects the short-term prognosis of
      acute variceal bleeding in cirrhotic patients. This study evaluated whether SVT
      also affects the rebleeding rate of patients included in a program of secondary
      prophylaxis after variceal bleeding. PATIENTS AND METHODS: A total of 387
      patients with variceal bleeding were included from January 2001 to December 2010.
      Band ligation was carried out every 3-4 weeks. Follow-up included endoscopy at 1,
      3, and every 6 months, Echo-Doppler, and biochemical examination every 6 months.
      From 2005, patients with SVT received anticoagulation with enoxaparin 200
      UI/kg/day for at least 6 months. The therapy was started after variceal
      eradication. RESULTS: SVT was diagnosed in 41 patients at variceal bleeding, in
      eight before and in 18 patients during the follow-up. Variceal eradication was
      achieved in 89.2 and 86.6% in no-SVT and SVT patients. Rebleeding occurred in 9.5
      and 11.9% of no-SVT and SVT patients at 12 months. Varices relapsed more
      frequently in SVT than in no-SVT patients (25.4 vs. 14.67%, P=0.03). The rates of
      variceal rebleeding and relapse were similar in patients who received or did not
      receive anticoagulation, but mortality was significantly lower in patients who
      received anticoagulation. CONCLUSION: SVT favors the relapse of esophageal
      varices, but rebleeding can be effectively prevented by standard scheduled band
      ligations. Anticoagulation does not prevent variceal relapse. The improvement in
      the survival of patients treated with anticoagulation needs to be confirmed in
      future studies.

PMID- 23114743
TI  - Association of insulin resistance, viral load, and adipokine levels with liver
      histology in patients with chronic hepatitis C:  an observational, multicenter
      study in Turkey.
AB  - OBJECTIVE: To evaluate the association of insulin resistance (IR), viral load,
      and adipokine levels with liver histology in patients with chronic hepatitis C
      (CHC). PATIENTS AND METHODS: In this noninterventional, multicenter study carried
      out at 11 infectious diseases clinics in Turkey, 103 CHC patients [mean (SD) age:
      50.2 (11.0) years, 60 (58.3%) women] planned to be treated by ribavirin and
      peginterferon-alpha2a were included. Data on hepatic fibrosis and steatosis, IR,
      viral load, and hepatitis C virus-RNA genotyping, adipokine, and cytokine levels
      were collected. RESULTS: The mean (SD) Knodell score was 8.1 (3.6); grade I
      steatosis was evident in 46 (44.7%) patients and IR was identified in 56 (54.9%).
      There was a significant positive correlation of the homeostasis model assessment
      IR index with Knodell fibrosis (r=0.235; P=0.027) and hepatic steatosis (r=0.435;
      P<0.001). There was a significant positive correlation of leptin levels with
      Knodell fibrosis (r=0.265; P=0.013) and hepatic activity index (r=0.218;
      P=0.041). Hepatic steatosis was correlated negatively with adiponectin (r=-0.320;
      P=0.001) and positively with leptin (r=-0.368; P<0.001) levels. Logistic
      regression analysis showed that increase in age [odds ratio (OR), 1.056; 95%
      confidence interval (CI), 1.005-1.110; P=0.030] was the only significant
      predictor of hepatic fibrosis (OR, 1.056; 95% CI, 1.005-1.110; P=0.030), whereas
      increase in age (OR, 1.066; 95% CI, 1.006-1.130; P=0.030), the presence of IR
      (OR, 5.621; 95% CI, 1.547-20.425; P=0.009), and decrease in adiponectin levels
      (OR, 0.808; 95% CI, 0.682-0.957; P=0.013) were the significant predictors of
      hepatic steatosis. CONCLUSION: Our findings indicate a significant relationship
      of hepatic fibrosis and hepatic steatosis with IR and leptin levels, but not with
      the viral load in Turkish patients with CHC.

PMID- 23114744
TI  - Prevalence of Helicobacter pylori infection and atrophic gastritis in Latvia.
AB  - OBJECTIVES: Helicobacter pylori infection and atrophic gastritis are related to
      an increased risk for gastric cancer. There is a decrease in global H. pylori
      prevalence. We analyzed the prevalence of H. pylori infection in Latvia by the
      plasma IgG test and the presence of atrophy by means of pepsinogen testing.
      METHODS: This subanalysis was carried out on a randomly selected cross-sectional
      sample of a general population of adults to access cardiovascular risk factors.
      Plasma samples were screened for H. pylori IgG (cutoff value 24 U/ml), and
      pepsinogens (Pg) I and II. Pg cutoff values of PgI/PgII <= 3 and PgI <= 70 ng/ml
      were used to assess the prevalence of atrophy of any grade and PgI/PgII <= 2 and
      PgI <= 30 ng/ml for advanced atrophy. RESULTS: Altogether, 3564 serum samples
      were available for the study (2346 women, 1218 men; median age 54 years). Of the
      tested individuals, 79.21% were H. pylori positive, with no difference between
      sexes. The prevalence increased with age (P<0.001). Atrophy of any grade was
      identified in 1444 individuals (40.52%) and advanced atrophy in 475 individuals
      (13.33%). Linear association with age was present in both response types
      (P<0.001). The prevalence of atrophy of any grade was higher in women (41.73%)
      than in men (38.18%; P=0.04); this difference was lost for advanced atrophy
      (women 13.98%, men 12.07%; P=0.1). CONCLUSION: The prevalence of H. pylori
      infection or atrophy remains high in Latvia. Determining the right cutoff value
      is critically important for pepsinogen-based atrophy detection in Europe in order
      to objectively stratify gastric cancer risk.

PMID- 23114745
TI  - Colorectal neuroendocrine carcinomas and adenocarcinomas share oncogenic
      pathways. A clinico-pathologic study of 12 cases.
AB  - OBJECTIVE: Neuroendocrine carcinomas (NECs) are rare neoplasms with an increasing
      incidence. Oncogenetic pathways of colorectal NEC are still poorly understood,
      and no treatment standards are available for these rare tumors. METHODS: We
      analyzed retrospectively the clinical records and histology of 12 patients with
      colorectal NEC. KRAS and BRAF mutations were investigated after the dissection of
      exoendocrine and neuroendocrine components. ALK alterations and EML4-ALK
      transcripts were detected by in-situ hybridization and determination of fusion
      transcripts, respectively. RESULTS: At the time of diagnosis, the mean age of the
      patients was 60 years (40-79) and 10 patients had synchronous metastases. A
      transient response occurred in two patients and one patient treated with
      cisplatin-etoposide or fluoropyrimidine-oxaliplatin, respectively. Tumor
      progression-related death occurred in 11 of 12 patients. Ten tumors contained an
      exocrine component, accounting for 5-70% of the tumor, and the other two
      contained an amphicrine component. BRAF/KRAS mutations were found in six of 10
      tumors, corresponding to BRAF(V600E) (n=2) or KRAS(G12D) (n=2), KRAS(G12V) or
      KRAS(G13D). DNA was obtained from both exocrine and endocrine components in seven
      cases, and the BRAF/KRAS status was identical in all cases. Split of the ALK
      locus was detected in a minority of tumor cells in two of eight cases, but EML4
      ALK transcripts were absent. CONCLUSION: The association of an exocrine component
      in all cases and the similar profile of BRAF/KRAS mutations indicate that
      colorectal NEC may correspond to a high-grade transformation of colorectal
      carcinoma. New chemotherapy regimens using targeted therapies should be assessed
      in these tumors.

PMID- 23114746
TI  - A multicentre study to determine the incidence, demographics, aetiology and
      outcomes of 6-day emergency readmission following day-case endoscopy.
AB  - BACKGROUND: Emergency readmission after elective procedures is a quality
      indicator of healthcare delivery, but data for endoscopy are limited. OBJECTIVES:
      Using hospital episode statistics (HES) registration systems and a multicentre
      audit to describe outcomes of emergency readmission following elective endoscopy.
      METHODS: Emergency readmissions (April 2008-2009) within 6 days of an elective
      day-case upper-GI endoscopy (UE) and lower GI endoscopy (LE) were subjected to a
      multicentre retrospective audit (north-west of England) following the
      identification of cases from routinely coded hospital administrative data from
      HES. RESULTS: Of 29 868 day cases, there were 235 readmissions, of which 147
      (63%) were endoscopy related. The overall endoscopy readmission rate was 0.5% and
      the highest for therapeutic UE (1.74%; P=0.0001). The rates for therapeutic LE,
      diagnostic UE and LE were 0.6, 0.5 and 0.4%, respectively. The incidence of
      readmission was 0.2% because of cardiorespiratory event, 0.14% for symptoms and
      0.08, 0.03, 0.02 and 0.016%, respectively, for bleeding, perforation, obstruction
      and nonrespiratory sepsis. Management was simple observation in 84.4%,
      intravenous antibiotics in 7.5%, surgery in 4.8% and repeat endoscopy in 2.7%.
      Although 24.5% were short-stay discharges, the mean hospital stay was 8.2 days.
      All-cause 30-day mortality was low at 0.06%, but was considerably higher in
      readmitted patients at 6.8% (P=0.0001). CONCLUSION: Novel insights into
      readmission rates can be gained following endoscopy using a combination of
      commercial analytical tools to examine HES data to identify eligible readmitted
      cases; multicentred patient-level audit readmission rates varied predictably
      across procedure types with cardiorespiratory events, the major cause. The risk
      of mortality in readmitted patients was significant.

PMID- 23114747
TI  - Quality assessment of endoscopic retrograde cholangiopancreatography:  results of
      a running nationwide Austrian benchmarking project after 5 years of
      implementation.
AB  - OBJECTIVE: Endoscopic retrograde cholangiopancreatography (ERCP) has a high risk
      of various complications. The aim of this study is to report the main ERCP
      outcome, that means complications and success rates, on the basis of the pooled
      data of a national continuous quality assessment program. METHODS: This study is
      an uncontrolled prospective survey and provides data from both academic and
      community-based endoscopy centers with varying case volumes and expertise. Data
      were collected within a nationwide voluntary ERCP benchmarking project that was
      initiated by the Austrian Society of Gastroenterology and Hepatology. RESULTS: In
      total, 42 sites participated in this program for varying periods (1 month up to 5
      years) and reported 13 513 procedures within 5 years. The overall complication
      rate in nonselected patients was 10.1%. Post-ERCP pancreatitis occurred in 4.2%,
      bleeding in 3.6% (0.4% clinically relevant), cholangitis in 1.4%, cardiopulmonary
      complications in 1.2%, perforation in 0.6%, and procedure-related deaths in 0.1%
      of procedures. The overall therapeutic and diagnostic target was achieved in
      80.3% (2009-2011) to 84.8% (2006/2007) of procedures. The desired duct was
      visualized in 90.7% and cannulated in 88.8% of procedures. CONCLUSION: The aim of
      the running benchmarking project in ERCP is to improve patient care in Austria.
      The survey reflects the general effectiveness and safety of ERCP. The overall
      complication and success rates are consistent with the available literature data.
      It sets an example as a benchmarking program that might result in international
      or even pan-European projects in high-risk endoscopic procedures.

PMID- 23114749
TI  - Hodgkin's lymphoma in a patient with cystic fibrosis: a clinical challenge.

PMID- 23114748
TI  - The incidence of inherited porphyrias in Europe.
AB  - Retrospective estimates of the prevalence of porphyrias have been reported but
      there has been no large scale prospective study of their incidence. The European
      Porphyria Network collected information prospectively over a 3 year period about
      the number of newly diagnosed symptomatic patients with an inherited porphyria
      (335 patients from 11 countries). Prevalence was calculated from the incidence
      and mean disease duration. The incidence of hepato-cellular carcinoma (HCC) in
      acute hepatic porphyria and the prevalence of patients with recurrent acute
      attacks of porphyria were also investigated. The incidence of symptomatic acute
      intermittent porphyria (AIP) was similar in all countries (0.13 per million per
      year; 95 % CI: 0.10 - 0.14) except Sweden (0.51; 95 % CI: 0.28-0.86). The
      incidence ratio for symptomatic AIP: variegate porphyria: hereditary
      coproporphyria was 1.00:0.62: 0.15. The prevalence of AIP (5.4 per million; 95 %
      CI: 4.5-6.3) was about half that previously reported. The prevalence of
      erythropoietic protoporphyria (EPP) was less uniform between countries and, in
      some countries, exceeded previous estimates. Fourteen new cases of HCC (11 from
      Sweden) were reported in patients with acute porphyria. Sixty seven patients (3
      VP; 64 AIP: 53 females, 11 males) with recurrent attacks of acute porphyria were
      identified. The estimated percentage of patients with AIP that will develop
      recurrent acute attacks was 3-5 %. In conclusion, the prevalence of symptomatic
      acute porphyria may be decreasing, possibly due to improved management, whereas
      the prevalence of EPP may be increasing due to improved diagnosis and its greater
      recognition as a cause of photosensitivity. 

PMID- 23114750
TI  - Rab-geranylgeranyl transferase regulates glucose-stimulated insulin secretion
      from pancreatic beta cells.
AB  - A growing body of evidence implicates essential roles for small molecular weight
      G-proteins (e.g., Cdc42, Rac1, Arf6 and Rab3A and Rab27A) in islet beta-cell
      function including glucose-stimulated insulin secretion (GSIS). One of the known
      mechanisms for optimal activation of small G-proteins involves post-translational
      prenylation, which is mediated by farnesyltransferase (FTase) and geranylgeranyl
      transferases (GGTases I and II). The FTase catalyzes incorporation of a 15-carbon
      farnesyl group while the GGTase mediates incorporation of a 20-carbon
      geranylgeranyl group into the C-terminal cysteines of G-proteins. The FTase,
      GGTase I and GGTase II prenylate Ras, Cdc42/Rac1, and Rab G-proteins,
      respectively. While considerable evidence exists on FTase/GGTase I-mediated
      regulation of GSIS, very little is known about GGTase II (also referred to as Rab
      GGTase; RGGT) and its regulatory proteins in the cascade of events leading to
      GSIS. Herein, we provide the first immunological evidence to suggest expression
      of alpha- and beta-subunits of RGGT in clonal INS 832/13 beta-cells, normal rat
      islets and human islets. Furthermore, Rab escort protein1 (REP1), which has been
      shown to be critical for prenylation of Rab G-proteins, is also expressed in
      these cells. Furthermore, evidence is presented to suggest that siRNA-mediated
      knockdown of alpha- or beta-subunits of RGGT and REP1 markedly attenuates GSIS in
      INS 832/13 cells. These findings provide the first evidence in support of key
      roles for RGGT and its regulatory proteins in GSIS.

PMID- 23114752
TI  - Interaction of platelets and anidulafungin against Aspergillus fumigatus.
AB  - The combination of platelets and anidulafungin at 0.03 MUg/ml significantly (P <
      0.05) reduced the germination rate and hyphal elongation in Aspergillus fumigatus
      compared to those with either anidulafungin only or an untreated control.
      Platelets decreased the expression of the fks gene, which plays an important role
      in cell wall synthesis. Our results suggest that human platelets plus
      anidulafungin might contribute to defense against A. fumigatus.

PMID- 23114751
TI  - Deregulated chromatin remodeling in the pathobiology of brain tumors.
AB  - Brain tumors encompass a heterogeneous group of malignant tumors with variable
      histopathology, aggressiveness, clinical outcome and prognosis. Current gene
      expression profiling studies indicate interplay of genetic and epigenetic
      alterations in their pathobiology. A central molecular event underlying
      epigenetics is the alteration of chromatin structure by post-translational
      modifications of DNA and histones as well as nucleosome repositioning. Dynamic
      remodeling of the fundamental nucleosomal structure of chromatin or covalent
      histone marks located in core histones regulate main cellular processes including
      DNA methylation, replication, DNA-damage repair as well as gene expression.
      Deregulation of these processes has been linked to tumor suppressor gene
      silencing, cancer initiation and progression. The reversible nature of
      deregulated chromatin structure by DNA methylation and histone deacetylation
      inhibitors, leading to re-expression of tumor suppressor genes, makes chromatin
      remodeling pathways as promising therapeutic targets. In fact, a considerable
      number of these inhibitors are being tested today either alone or in combination
      with other agents or conventional treatments in the management of brain tumors
      with considerable success. In this review, we focus on the mechanisms
      underpinning deregulated chromatin remodeling in brain tumors, discuss their
      potential clinical implications and highlight the advances toward new therapeutic
      strategies.

PMID- 23114753
TI  - Inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and application of
      statins as a novel effective therapeutic approach against Acanthamoeba
      infections.
AB  - Acanthamoeba is an opportunistic pathogen in humans, whose infections most
      commonly manifest as Acanthamoeba keratitis or, more rarely, granulomatous
      amoebic encephalitis. Although there are many therapeutic options for the
      treatment of Acanthamoeba, they are generally lengthy and/or have limited
      efficacy. Therefore, there is a requirement for the identification, validation,
      and development of novel therapeutic targets against these pathogens. Recently,
      RNA interference (RNAi) has been widely used for these validation purposes and
      has proven to be a powerful tool for Acanthamoeba therapeutics. Ergosterol is one
      of the major sterols in the membrane of Acanthamoeba. 3-Hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase is an enzyme that catalyzes the conversion of HMG
      CoA to mevalonate, one of the precursors for the production of cholesterol in
      humans and ergosterol in plants, fungi, and protozoa. Statins are compounds which
      inhibit this enzyme and so are promising as chemotherapeutics. In order to
      validate whether this enzyme could be an interesting therapeutic target in
      Acanthamoeba, small interfering RNAs (siRNAs) against HMG-CoA were developed and
      used to evaluate the effects induced by the inhibition of Acanthamoeba HMG-CoA.
      It was found that HMG-CoA is a potential drug target in these pathogenic free
      living amoebae, and various statins were evaluated in vitro against three
      clinical strains of Acanthamoeba by using a colorimetric assay, showing important
      activities against the tested strains. We conclude that the targeting of HMG-CoA
      and Acanthamoeba treatment using statins is a novel powerful treatment option
      against Acanthamoeba species in human disease.

PMID- 23114754
TI  - Relative to quinine and quinidine, their 9-epimers exhibit decreased cytostatic
      activity and altered heme binding but similar cytocidal activity versus
      Plasmodium falciparum.
AB  - The 9-epimers of quinine (QN) and quinidine (QD) are known to exhibit poor
      cytostatic potency against P. falciparum (Karle JM, Karle IL, Gerena L, Milhous
      WK, Antimicrob. Agents Chemother. 36:1538-1544, 1992). We synthesized 9-epi-QN
      (eQN) and 9-epi-QD (eQD) via Mitsunobu esterification-saponification and
      evaluated both cytostatic and cytocidal antimalarial activities. Relative to the
      cytostatic activity of QN and QD, we observed a large decrease in cytostatic
      activity (higher 50% inhibitory concentration [IC(50)s]) against QN-sensitive
      strain HB3, QN-resistant strain Dd2, and QN-hypersensitive strain K76I,
      consistent with previous work. However, we observed relatively small changes in
      cytocidal activity (the 50% lethal dose), similar to observations with
      chloroquine (CQ) analogues with a wide range of IC(50)s (see the accompanying
      paper [A. P. Gorka, J. N. Alumasa, K. S. Sherlach, L. M. Jacobs, K. B. Nickley,
      J. P. Brower, A. C. de Dios, and P. D. Roepe, Antimicrob. Agents Chemother.
      57:356-364, 2013]). Compared to QN and QD, the 9-epimers had significantly
      reduced hemozoin inhibition efficiency and did not affect pH-dependent
      aggregation of ferriprotoporphyrin IX (FPIX) heme. Magnetic susceptibility
      measurements showed that the 9-epimers perturb FPIX monomer-dimer equilibrium in
      favor of monomer, and UV-visible (VIS) titrations showed that eQN and eQD bind
      monomer with similar affinity relative to QN and QD. However, unique ring proton
      shifts in the presence of zinc(II) protoporphyrin IX (ZnPIX) indicate that
      binding of the 9-epimers to monomeric heme is via a distinct geometry. We
      isolated eQN- and eQD-FPIX complexes formed under aqueous conditions and analyzed
      them by mass, fluorescence, and UV-VIS spectroscopies. The 9-epimers produced low
      fluorescent adducts with a 2:1 stoichiometry (drug to FPIX) which did not survive
      electrospray ionization, in contrast to QN and QD complexes. The data offer
      important insight into the relevance of heme interactions as a drug target for
      cytostatic versus cytocidal dosages of quinoline antimalarial drugs and further
      elucidate a surprising structural diversity of quinoline antimalarial drug-heme
      complexes.

PMID- 23114755
TI  - Point mutations within the fatty acid synthase type II dehydratase components
      HadA or HadC contribute to isoxyl resistance in Mycobacterium tuberculosis.
AB  - The mechanism by which the antitubercular drug isoxyl (ISO) inhibits mycolic acid
      biosynthesis has not yet been reported. We found that point mutations in either
      the HadA or HadC component of the type II fatty acid synthase (FAS-II) are
      associated with increased levels of resistance to ISO in Mycobacterium
      tuberculosis. Overexpression of the HadAB, HadBC, or HadABC heterocomplex also
      produced high-level resistance. These results show that the FAS-II dehydratases
      are involved in ISO resistance.

PMID- 23114756
TI  - Low-level persistence of drug resistance mutations in hepatitis B virus-infected
      subjects with a past history of Lamivudine treatment.
AB  - We sought to determine the prevalence of hepatitis B virus (HBV) lamivudine (LAM)
      resistant minority variants in subjects who once received LAM but had
      discontinued it prior to virus sampling. We performed direct PCR Sanger
      sequencing and ultradeep pyrosequencing (UDPS) of HBV reverse transcriptase (RT)
      of plasma viruses from 45 LAM-naive subjects and 46 LAM-experienced subjects who
      had discontinued LAM a median of 24 months earlier. UDPS was performed to a depth
      of ~3,000 reads per nucleotide. Minority variants were defined as differences
      from the Sanger sequence present in >=0.5% of UDPS reads in a sample. Sanger
      sequencing identified >=1 LAM resistance mutations (rtL80I/V, rtM204I, and
      rtA181T) in samples from 5 (11%) of 46 LAM-experienced and none of 45 LAM-naive
      subjects (0%; P = 0.06). UDPS detected >=1 LAM resistance mutations (rtL80I/V,
      rtV173L, rtL180M, rtA181T, and rtM204I/V) in 10 (22%) of the 46 LAM-experienced
      subjects, including 5 in whom LAM resistance mutations were not identified by
      Sanger sequencing. Overall, LAM resistance mutations were more likely to be
      present in LAM-experienced (10/46, 22%) than LAM-naive subjects (0/45, 0%; P =
      0.001). The median time since LAM discontinuation was 12.8 months in the 10
      subjects with a LAM resistance mutation compared to 30.5 months in the 36 LAM
      experienced subjects without a LAM resistance mutation (P < 0.001). The
      likelihood of detecting a LAM resistance mutation was significantly increased
      using UDPS compared to Sanger sequencing and was inversely associated with the
      time since LAM discontinuation.

PMID- 23114758
TI  - Outcome of debridement and retention in prosthetic joint infections by
      methicillin-resistant staphylococci, with special reference to rifampin and
      fusidic acid combination therapy.
AB  - The management of prosthetic joint infections remains a clinical challenge,
      particularly infections due to methicillin-resistant staphylococci. Previously,
      this infection was considered a contraindication to debridement and retention
      strategies. This retrospective cohort study examined the treatment and outcomes
      of patients with arthroplasty infection by methicillin-resistant staphylococci
      managed by debridement and retention in conjunction with rifampin-fusidic acid
      combination therapy. Over an 11-year period, there were 43 patients with
      infection by methicillin-resistant staphylococci managed with debridement and
      retention. This consisted of close-interval repeated arthrotomies with pulsatile
      lavage. Rifampin was combined with fusidic acid for the majority of patients
      (88%). Patients were monitored for a median of 33.5 months (interquartile range,
      20 to 54 months). Overall, 9 patients experienced treatment failure, with 12- and
      24-month estimates of infection-free survival of 86% (95% confidence interval
      [CI], 71 to 93%) and 77% (95% CI, 60 to 87%), respectively. The following factors
      were associated with treatment failure: methicillin-resistant Staphylococcus
      aureus (MRSA) arthroplasty infection, a single surgical debridement or >=4
      debridements, and the receipt of less than 90 days of antibiotic therapy.
      Patients with infection by methicillin-resistant coagulase-negative staphylococci
      (MR-CNS) were less likely to fail treatment. The overall treatment success rate
      reported in this study is comparable to those of other treatment modalities for
      prosthetic joint infections by methicillin-resistant staphylococci. Therefore,
      the debridement and retention of the prosthesis and rifampin-based antibiotic
      therapy are a valid treatment option for carefully selected patients.

PMID- 23114759
TI  - The target of daptomycin is absent from Escherichia coli and other gram-negative
      pathogens.
AB  - Antistaphylococcal agents commonly lack activity against Gram-negative bacteria
      like Escherichia coli owing to the permeability barrier presented by the outer
      membrane and/or the action of efflux transporters. When these intrinsic
      resistance mechanisms are artificially compromised, such agents almost invariably
      demonstrate antibacterial activity against Gram negatives. Here we show that this
      is not the case for the antibiotic daptomycin, whose target appears to be absent
      from E. coli and other Gram-negative pathogens.

PMID- 23114757
TI  - Whole-genome analysis of a daptomycin-susceptible enterococcus faecium strain and
      its daptomycin-resistant variant arising during therapy.
AB  - Development of daptomycin (DAP) resistance in Enterococcus faecalis has recently
      been associated with mutations in genes encoding proteins with two main
      functions: (i) control of the cell envelope stress response to antibiotics and
      antimicrobial peptides (LiaFSR system) and (ii) cell membrane phospholipid
      metabolism (glycerophosphoryl diester phosphodiesterase and cardiolipin synthase
      [cls]). However, the genetic bases for DAP resistance in Enterococcus faecium are
      unclear. We performed whole-genome comparative analysis of a clinical strain
      pair, DAP-susceptible E. faecium S447 and its DAP-resistant derivative R446,
      which was recovered from a single patient during DAP therapy. By comparative
      whole-genome sequencing, DAP resistance in R446 was associated with changes in 8
      genes. Two of these genes encoded proteins involved in phospholipid metabolism:
      (i) an R218Q substitution in Cls and (ii) an A292G reversion in a putative
      cyclopropane fatty acid synthase enzyme. The DAP-resistant derivative R446 also
      exhibited an S333L substitution in the putative histidine kinase YycG, a member
      of the YycFG system, which, similar to LiaFSR, has been involved in cell envelope
      homeostasis and DAP resistance in other Gram-positive cocci. Additional changes
      identified in E. faecium R446 (DAP resistant) included two putative proteins
      involved in transport (one for carbohydrate and one for sulfate) and three
      enzymes predicted to play a role in general metabolism. Exchange of the
      "susceptible" cls allele from S447 for the "resistant" one belonging to R446 did
      not affect DAP susceptibility. Our results suggest that, apart from the LiaFSR
      system, the essential YycFG system is likely to be an important mediator of DAP
      resistance in some E. faecium strains.

PMID- 23114760
TI  - GES-18, a new carbapenem-hydrolyzing GES-Type beta-lactamase from Pseudomonas
      aeruginosa that contains Ile80 and Ser170 residues.
AB  - A clinical isolate of Pseudomonas aeruginosa recovered from the lower respiratory
      tract of an 81-year-old patient hospitalized in Belgium was sent to the national
      reference center to determine its resistance mechanism. PCR sequencing identified
      a new GES variant, GES-18, which differs from the carbapenem-hydrolyzing enzyme
      GES-5 by a single amino acid substitution (Val80Ile, in the numbering according
      to Ambler) and from GES-1 by two substitutions (Val80Ile and Gly170Ser). Detailed
      kinetic characterization showed that GES-18 and GES-5 hydrolyze imipenem and
      cefoxitin with similar kinetic parameters and that GES-18 was less susceptible
      than GES-1 to classical beta-lactamase inhibitors such as clavulanate and
      tazobactam. The overall structure of GES-18 is similar to the solved structures
      of GES-1 and GES-2, the Val80Ile and Gly170Ser substitutions causing only subtle
      local rearrangements. Notably, the hydrolytic water molecule and the Glu166
      residue were slightly displaced compared to their counterparts in GES-1. Our
      kinetic and crystallographic data for GES-18 highlight the pivotal role of the
      Gly170Ser substitution which distinguishes GES-5 and GES-18 from GES-1.

PMID- 23114761
TI  - Molecular identification, antifungal susceptibility profile, and biofilm
      formation of clinical and environmental Rhodotorula species isolates.
AB  - Rhodotorula species are emergent fungal pathogens capable of causing invasive
      infections, primarily fungemia. They are particularly problematic in
      immunosuppressed patients when using a central venous catheter. In this study, we
      evaluated the species distribution of 51 clinical and 8 environmental Rhodotorula
      species isolates using the ID32C system and internal transcribed spacer (ITS)
      sequencing. Antifungal susceptibility testing and biofilm formation capability
      using a crystal violet staining assay were performed. Using ITS sequencing as the
      gold standard, the clinical isolates were identified as follows: 44 R.
      mucilaginosa isolates, 2 R. glutinis isolates, 2 R. minuta isolates, 2 R.
      dairenensis isolates, and 1 Rhodosporidium fluviale isolate. The environmental
      isolates included 7 R. mucilaginosa isolates and 1 R. slooffiae isolate. Using
      the ID32C system, along with a nitrate assimilation test, only 90.3% of the
      isolates tested were correctly identified. In the biofilm formation assay, R.
      mucilaginosa and R. minuta exhibited greater biofilm formation ability compared
      to the other Rhodotorula species; the clinical isolates of R. mucilaginosa showed
      greater biofilm formation compared to the environmental isolates (P = 0.04).
      Amphotericin B showed good in vitro activity (MIC <= 1 MUg/ml) against planktonic
      cells, whereas voriconazole and posaconazole showed poor activity
      (MIC(50)/MIC(90), 2/4 MUg/ml). Caspofungin and fluconazole MICs were consistently
      high for all isolates tested (>=64 MUg/ml and >= 4 MUg/ml, respectively). In this
      study, we emphasized the importance of molecular methods to correctly identify
      Rhodotorula species isolates and non-R. mucilaginosa species in particular. The
      antifungal susceptibility profile reinforces amphotericin B as the antifungal
      drug of choice for the treatment of Rhodotorula infections. To our knowledge,
      this is the first study evaluating putative differences in the ability of biofilm
      formation among different Rhodotorula species.

PMID- 23114763
TI  - Benznidazole-related adverse drug reactions and their relationship to serum drug
      concentrations in patients with chronic chagas disease.
AB  - For treating Chagas disease (CD), a current worldwide health problem, only
      benznidazole and nifurtimox have been approved to be used. In both cases,
      unwanted drug-related adverse events (ADRs) are frequent when these drugs are
      used in adults in the chronic stage. The main objective of this study was to
      establish benznidazole ADRs and their relationship to serum concentrations in
      patients with chronic Trypanosoma cruzi infection in order to perform more
      accurate dosages to minimize ADRs. A total of 54 patients were recruited over 12
      months. Of these 54 patients, 53 (98%) experienced at least one ADR during follow
      up, and the overall average ADR incidence was 2.4 episodes/patient/month.
      Benznidazole treatment was discontinued in 11 patients, 7 among them due to
      severe adverse effects. The mean duration of treatment before withdrawal was 11
      days. Benznidazole serum concentrations were recorded on days 15, 30, 45, and 60
      of follow-up and evaluated according to clinical and epidemiological variables
      and ADR severity. No relationship was found between the benznidazole serum
      concentration and the ADRs. The mean (standard deviation) trough serum
      benznidazole concentrations (all below 20 mcg/ml) on days 15, 30, 45, and 60 were
      6.4 (1.9), 6.1 (1.8), 6.2 (2.2), and 5.7 (1.7) MUg/ml, respectively. Benznidazole
      serum concentrations do not appear to be related to the appearance of serious
      ADRs. Further, well-controlled studies are necessary to establish the optimal
      regimen for benznidazole in adults with chronic CD.

PMID- 23114762
TI  - FIM-1, a new acquired metallo-beta-lactamase from a Pseudomonas aeruginosa
      clinical isolate from Italy.
AB  - Acquired metallo-beta-lactamases (MBLs) are resistance determinants of increasing
      clinical importance in Gram-negative bacterial pathogens, which confer a broad
      spectrum beta-lactam resistance, including carbapenems. Several such enzymes have
      been described since the 1990s. In the present study, a novel acquired MBL, named
      FIM-1, was identified and characterized. The bla(FIM-1) gene was cloned from a
      multidrug-resistant Pseudomonas aeruginosa clinical isolate (FI-14/157) cultured
      from a patient with a vascular graft infection in Florence, Italy. The isolate
      belonged in the sequence type 235 epidemic clonal lineage. The FIM-1 enzyme is a
      member of subclass B1 and, among acquired MBLs, exhibited the highest similarity
      (ca. 40% amino acid identity) with NDM-type enzymes. In P. aeruginosa FI-14/157,
      the bla(FIM-1) gene was apparently inserted into the chromosome and associated
      with ISCR19-like elements that were likely involved in the capture and
      mobilization of this MBL gene. Transfer experiments of the bla(FIM-1) gene to an
      Escherichia coli strain or another P. aeruginosa strain by conjugation or
      electrotransformation were not successful. The FIM-1 protein was produced in E.
      coli and purified by two chromatography steps. Analysis of the kinetic
      parameters, carried out with the purified enzyme, revealed that FIM-1 has a broad
      substrate specificity, with a preference for penicillins (except the 6alpha
      methoxy derivative temocillin) and carbapenems. Aztreonam was not hydrolyzed.
      Detection of this novel type of acquired MBL in a P. aeruginosa clinical isolate
      underscores the increasing diversity of such enzymes that can be encountered in
      the clinical setting.

PMID- 23114764
TI  - Tigecycline displays in vivo bactericidal activity against extended-spectrum-beta
      lactamase-producing Enterobacteriaceae after 72-hour exposure period.
AB  - Progressively enhanced activity of a humanized tigecycline (TGC) regimen was
      noted over 3 days against an extended-spectrum-beta-lactamase (ESBL)-producing
      Escherichia coli isolate and an ESBL-producing Klebsiella pneumoniae isolate.
      Bacterial density reduction approximated 3 log(10) approaching bactericidal
      activity at 72 h. This level of activity has not been previously noted for
      compounds such as tetracyclines, normally considered bacteriostatic
      antimicrobials. Extended regimen studies in vivo may aid in better delineation of
      antimicrobial effects, producing improved correlation with clinical outcomes.

PMID- 23114765
TI  - Novel apidaecin 1b analogs with superior serum stabilities for treatment of
      infections by gram-negative pathogens.
AB  - Proline-rich antimicrobial peptides (PrAMPs) from insects and mammals have
      recently been evaluated for their pharmaceutical potential in treating systemic
      bacterial infections. Besides the native peptides, several shortened, modified,
      or even artificial sequences were highly effective in different murine infection
      models. Most recently, we showed that the 18-residue-long peptide Api88, an
      optimized version of apidaecin 1b, was efficient in two different animal
      infection models using the pathogenic Escherichia coli strains ATCC 25922 and
      Neumann, with a promising safety margin. Here, we show that Api88 is degraded
      relatively fast upon incubation with mouse serum, by cleavage of the C-terminal
      leucine residue. To improve its in vitro characteristics, we aimed to improve its
      serum stability. Replacing the C-terminal amide by the free acid or substituting
      Arg-17 with l-ornithine or l-homoarginine increased the serum stabilities by more
      than 20-fold (half-life, ~4 to 6 h). These analogs were nontoxic to human
      embryonic kidney (HEK 293), human hepatoma (HepG2), SH-SY5Y, and HeLa cells and
      nonhemolytic to human erythrocytes. The binding constants of all three analogs
      with the chaperone DnaK, which is proposed as the bacterial target of PrAMPs,
      were very similar to that of Api88. Of all the analogs tested, Api137 (Gu
      ONNRPVYIPRPRPPHPRL; Gu is N,N,N',N'-tetramethylguanidino) appeared most promising
      due to its high antibacterial activity, which was very similar to Api88.
      Positional alanine and d-amino acid scans of Api137 indicated that substitutions
      of residues 1 to 13 had only minor effects on the activity against an E. coli
      strain, whereas substitutions of residues 14 to 18 decreased the activity
      dramatically. Based on the significantly improved resistance to proteolysis,
      Api137 appears to be a very promising lead compound that should be even more
      efficient in vivo than Api88.

PMID- 23114766
TI  - Characterization of OXA-204, a carbapenem-hydrolyzing class D beta-lactamase from
      Klebsiella pneumoniae.
AB  - A Klebsiella pneumoniae clinical isolate recovered in Tunisia showed resistance
      to all beta-lactams and decreased susceptibility to carbapenems. K. pneumoniae
      204 expressed the carbapenem-hydrolyzing beta-lactamase OXA-204, differing from
      OXA-48 by two amino acid substitutions (Gln98His and Thr99Arg) (class D beta
      lactamase [DBL] numbering). OXA-48 and OXA-204 shared similar resistance
      profiles, hydrolyzing carbapenems but sparing broad-spectrum cephalosporins. The
      bla(OXA-204) gene was located on a ca. 150-kb IncA/C-type plasmid, which also
      carried the bla(CMY-4) gene. The bla(OXA-204) gene was associated with an ISEcp1
      element, whereas the bla(OXA-48) genes are usually associated with IS1999.

PMID- 23114767
TI  - Comparative genomics of IncL/M-type plasmids: evolution by acquisition of
      resistance genes and insertion sequences.

PMID- 23114768
TI  - Effects of etravirine on the pharmacokinetics of the integrase inhibitor
      S/GSK1265744.
AB  - HIV integrase inhibitors such as raltegravir and elvitegravir halt HIV
      progression, but treatment-emergent resistance and cross-resistance have been
      observed. The nonnucleoside reverse transcriptase inhibitor etravirine (ETR) may
      be used in combination with integrase inhibitors in patients with drug
      resistance. This single-center, open-label, two-period, single-sequence crossover
      study evaluated the effects of ETR coadministration on the pharmacokinetic
      profile of S/GSK1265744, an investigational integrase inhibitor in phase 2
      studies. Healthy subjects received 30 mg of S/GSK1265744 alone once daily for 10
      days (period 1) and in combination with 200 mg of ETR twice daily for 14 days
      (period 2). Serial plasma samples for pharmacokinetic analyses were collected on
      day 10 during period 1 and on day 14 during period 2. All treatments were well
      tolerated. Etravirine had no effects on S/GSK1265744 geometric mean ratios of the
      area under the curve from time zero until the end of the dosing interval (1.01;
      90% confidence interval [CI], 0.956 to 1.06), of the maximum observed plasma
      concentration (1.04; 90% CI, 0.987 to 1.09), or of the plasma concentration at
      the end of the dosing interval (0.999; 90% CI, 0.942 to 1.06). Etravirine
      pharmacokinetics (PK) parameters observed following coadministration with
      S/GSK1265744 were in the range of historical values reported for ETR alone in
      healthy subjects. These results indicate that 30 mg of S/GSK1265744 for 10 days
      as monotherapy followed by an additional 14 days in combination with ETR was well
      tolerated in healthy subjects and that no dose adjustment of S/GSK1265744 is
      required when it is coadministered with ETR.

PMID- 23114769
TI  - Characterization of recombinant fluoroquinolone-resistant pneumococcus-like
      isolates.
AB  - Fourteen fluoroquinolone-resistant streptococcal isolates with recombinant DNA
      topoisomerase genes, preliminarily identified as pneumococci, were further
      characterized using phenotypic and genotypic approaches. Phenotypic tests
      classified them as atypical pneumococci. Phylogenetic relationships were analyzed
      by using the sequences of seven housekeeping alleles from these isolates and from
      isolates of Streptococcus pneumoniae, Streptococcus mitis, Streptococcus oralis,
      and Streptococcus pseudopneumoniae. Four isolates grouped with S. pneumoniae,
      seven grouped with S. pseudopneumoniae, and three grouped with S. mitis. These
      results generally agreed with those obtained with an optochin susceptibility test
      and with the organization of the atp operon chromosomal region, encoding the
      F(o)F(1) H(+)-ATPase (the target of optochin). All seven isolates grouping with
      S. pseudopneumoniae share the same spr1368-atpC-atpA gene order; all four
      grouping with S. pneumoniae share the spr1368-IS1239-atpC-atpA order, and two out
      of the three grouping with S. mitis share the spr1284-atpC-atpA order. In
      addition, evidence for recombination within the seven housekeeping alleles of the
      S. pseudopneumoniae population was provided by several methods: the index of
      association (0.4598, P < 0.001), the pairwise homoplasy index, and the split
      decomposition method. This study confirms the existence of pneumococci among the
      alpha-hemolytic streptococci with DNA topoisomerase genes showing a mosaic
      structure and reveals a close relationship between atypical pneumococci and S.
      pseudopneumoniae.

PMID- 23114770
TI  - Complete nucleotide sequences of blaKPC-4- and blaKPC-5-harboring IncN and IncX
      plasmids from Klebsiella pneumoniae strains isolated in New Jersey.
AB  - Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae have
      emerged as major nosocomial pathogens. bla(KPC), commonly located on Tn4401, is
      found in Gram-negative bacterial strains, with the two most common variants,
      bla(KPC-2) and bla(KPC-3), identified in plasmids with diverse genetic
      backgrounds. In this study, we examined bla(KPC-4)- and bla(KPC-5)-bearing
      plasmids recovered from two K. pneumoniae strains, which were isolated from a
      single New Jersey hospital in 2005 and 2006, respectively. IncN plasmid pBK31551
      is 84 kb in length and harbors bla(KPC-4), bla(TEM-1), qnrB2, aac(3)-Ib, aph(3')
      I, qacF, qacEDelta1, sul1, and dfrA14, which confer resistance to beta-lactams,
      quinolones, aminoglycosides, quaternary ammonium compounds, and co-trimoxazole.
      The conserved regions within pBK31551 are similar to those of other IncN
      plasmids. Surprisingly, analysis of the Tn4401 sequence revealed a large IS110-
      and Tn6901-carrying element (8.3 kb) inserted into the istA gene, encoding
      glyoxalase/bleomycin resistance, alcohol dehydrogenase, and S-formylglutathione
      hydrolase. Plasmid pBK31567 is 47 kb in length and harbors bla(KPC-5), dfrA5,
      qacEDelta1, and sul1. pBK31567 belongs to a novel IncX subgroup (IncX5) and
      possesses a highly syntenic plasmid backbone like other IncX plasmids; however,
      sequence similarity at the nucleotide level is divergent. The bla(KPC-5) gene is
      carried on a Tn4401 element and differs from the genetic environment of bla(KPC
      5) described in Pseudomonas aeruginosa strain P28 from Puerto Rico. This study
      underscores the genetic diversity of multidrug-resistant plasmids involved in the
      spread of bla(KPC) genes and highlights the mobility and plasticity of Tn4401.
      Comparative genomic analysis provides new insights into the evolution and
      dissemination of KPC plasmids belonging to different incompatibility groups.

PMID- 23114771
TI  - Highly variable plasma concentrations of voriconazole in pediatric hematopoietic
      stem cell transplantation patients.
AB  - Invasive fungal infections are of great concern in pediatric hematopoietic stem
      cell transplantation (HSCT) recipients. Voriconazole is usually the drug of first
      choice for treating or preventing invasive aspergillosis. Optimum trough levels
      (C(trough)s) are between 1 and 5 mg/liter. It is unclear whether these levels are
      reached with currently advised pediatric dosing schedules. Between 2007 and 2011,
      11 patients <2 years of age, 31 between 2 and 12 years, and 20 between 12 and 20
      years were (prophylactically or therapeutically) treated with voriconazole in the
      HSCT unit of UMC Utrecht. For children <2 years of age, the dosage recommended
      for 2 to 12 years was used. In 34% of children who started with the recommended
      dose, an adequate C(trough) was reached irrespective of age or administration
      route. After therapeutic drug monitoring (TDM)-based dose adjustments, adequate
      C(trough)s were reached in 80% of the patients at median doses of 31.5 (age, <2
      years), 16 (age, 2 to 12 years), and 9.4 mg/kg of body weight/day (age, >12
      years) (P = 0.034). The intrapatient variability in C(trough) ranged between 1
      and 238%. Voriconazole was discontinued in six patients due to toxicity. These
      patients had a median C(trough) of 0.5 mg/liter at the initial dose (ranging from
      0.5 to 2.6 mg/liter), and a medium maximal concentration of 4 mg/liter was
      reached. Inter- and intrapatient variability is a major concern in voriconazole
      treatment and necessitates therapeutic drug monitoring of dosing, especially in
      young children.

PMID- 23114772
TI  - Rapid isolation and susceptibility testing of Leptospira spp. using a new solid
      medium, LVW agar.
AB  - Pathogenic Leptospira spp., the causative agents of leptospirosis, are slow
      growing Gram-negative spirochetes. Isolation of Leptospira from clinical samples
      and testing of antimicrobial susceptibility are difficult and time-consuming.
      Here, we describe the development of a new solid medium that facilitates more
      rapid growth of Leptospira spp. and the use of this medium to evaluate the
      Etest's performance in determining antimicrobial MICs to drugs in common use for
      leptospirosis. The medium was developed by evaluating the effects of numerous
      factors on the growth rate of Leptospira interrogans strain NR-20157. These
      included the type of base agar, the concentration of rabbit serum (RS), and the
      concentration and duration of CO(2) incubation during the initial period of
      culture. The highest growth rate of NR-20157 was achieved using a Noble agar base
      supplemented with 10% RS (named LVW agar), with an initial incubation at 30
      degrees C in 5% CO(2) for 2 days prior to continuous culture in air at 30 degrees
      C. These conditions were used to develop the Etest for three species, L.
      interrogans (NR-20161), L. kirschnerii (NR-20327), and L. borgpetersenii (NR
      20151). The MICs were read on day 7 for all samples. The Etest was then performed
      on 109 isolates of pathogenic Leptospira spp. The MIC(90) values for penicillin
      G, doxycycline, cefotaxime, ceftriaxone, and chloramphenicol were 0.64 units/ml
      and 0.19, 0.047, 0.5, and 2 MUg/ml, respectively. The use of LVW agar, which
      enables rapid growth, isolation of single colonies, and simple antimicrobial
      susceptibility testing for Leptospira spp., provides an opportunity for new areas
      of fundamental and applied research.

PMID- 23114773
TI  - Pharmacodynamics of anidulafungin against clinical Aspergillus fumigatus isolates
      in a nonneutropenic murine model of disseminated aspergillosis.
AB  - Azole resistance is an emerging increasing problem in Aspergillus fumigatus that
      results in treatment failure. Alternative treatments may improve the therapeutic
      outcome in patients with azole-resistant invasive aspergillosis (IA). Little is
      known about the in vivo efficacy of the echinocandin anidulafungin (AFG) in IA.
      The in vivo efficacy of 2.5, 5, 10, and 20 mg/kg of body weight AFG was assessed
      against two clinical Aspergillus fumigatus isolates with identical AFG minimum
      effective concentrations (MECs; 0.03 mg/liter) in a murine model of IA: a wild
      type voriconazole (VCZ)-susceptible (VCZ(s)) A. fumigatus isolate (AZN 8196) and
      a VCZ-resistant (VCZ(r)) A. fumigatus isolate (V52-35) harboring the TR(34)/L98H
      resistance mechanism (substitution at codon L98 in combination with a 34-bp
      tandem repeat in the promoter region of the CYP51A gene). The pharmacokinetics of
      AFG were also assessed for each dose. Increasing doses increased survival for
      both isolates in a manner dependent on the AFG dose level (R(2) = 0.99 and 0.95,
      respectively) up to a maximum of 72.7% and 45.45% for the VCZ(s) and VCZ(r)
      isolates, respectively. The area under the concentration-time curve (AUC)
      correlated significantly with the dose in a linear fashion over the entire dosing
      range (R(2) = 0.86). The Hill equation with a variable slope fitted the
      relationship between the 24-h AUC/MEC ratio and 14-day survival well (R(2) =
      0.87; P < 0.05). The 50% effective AUC/MEC for total AFG was 126.5 (95%
      confidence interval, 79.09 to 202.03). AFG treatment improved the survival of
      mice in a dose-dependent manner; however, a maximal response was not achieved
      with either isolate even in those treated with the highest AFG dose.

PMID- 23114775
TI  - 18beta-Glycyrrhetinic acid inhibits methicillin-resistant Staphylococcus aureus
      survival and attenuates virulence gene expression.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) has become a major source of
      infection in hospitals and in the community. Increasing antibiotic resistance in
      S. aureus strains has created a need for alternative therapies to treat disease.
      A component of the licorice root Glycyrrhiza spp., 18beta-glycyrrhetinic acid
      (GRA), has been shown to have antiviral, antitumor, and antibacterial activity.
      This investigation explores the in vitro and in vivo effects of GRA on MRSA
      pulsed-field gel electrophoresis (PFGE) type USA300. GRA exhibited bactericidal
      activity at concentrations exceeding 0.223 MUM. Upon exposure of S. aureus to
      sublytic concentrations of GRA, we observed a reduction in expression of key
      virulence genes, including saeR and hla. In murine models of skin and soft tissue
      infection, topical GRA treatment significantly reduced skin lesion size and
      decreased the expression of saeR and hla genes. Our investigation demonstrates
      that at high concentrations GRA is bactericidal to MRSA and at sublethal doses it
      reduces virulence gene expression in S. aureus both in vitro and in vivo.

PMID- 23114776
TI  - In vitro activity and durability of a combination of an antibiofilm and an
      antibiotic against vascular catheter colonization.
AB  - Catheter-associated infections can cause severe complications and even death.
      Effective antimicrobial modification of catheters that can prevent device
      colonization has the potential of preventing clinical infection. We studied in
      vitro the antimicrobial activities of central venous catheters impregnated with N
      acetylcysteine (NAC), an antibiofilm agent, and a broad-spectrum antibiotic
      against a range of important clinical pathogens. NAC-levofloxacin-impregnated
      (NACLEV) catheters were also evaluated for their antiadherence activity. NACLEV
      catheters produced the most active and durable antimicrobial effect against both
      Gram-positive and Gram-negative isolates and significantly reduced colonization
      (P < 0.0001) by all tested pathogens compared to control catheters. These in
      vitro results suggest that this antimicrobial combination can potentially be used
      to combat catheter colonization and catheter-associated infection.

PMID- 23114774
TI  - Clonal structure, extended-spectrum beta-lactamases, and acquired AmpC-type
      cephalosporinases of Escherichia coli populations colonizing patients in
      rehabilitation centers in four countries.
AB  - The prospective project MOSAR was conducted in five rehabilitation units: the
      Berck Maritime Hopital (Berck, France), Fondazione Santa Lucia (Rome, Italy),
      Guttmann Institute (GI; Barcelona, Spain), and Loewenstein Hospital and Tel-Aviv
      Souraski Medical Center (TA) (Tel-Aviv, Israel). Patients were screened for
      carriage of Enterobacteriaceae resistant to expanded-spectrum cephalosporins
      (ESCs) from admission until discharge. The aim of this study was to characterize
      the clonal structure, extended-spectrum beta-lactamases (ESBLs), and acquired
      AmpC-like cephalosporinases in the Escherichia coli populations collected. A
      total of 376 isolates were randomly selected. The overall number of sequence
      types (STs) was 76, including 7 STs that grouped at least 10 isolates from at
      least three centers each, namely, STs 10, 38, 69, 131, 405, 410, and 648. These
      clones comprised 65.2% of all isolates, and ST131 alone comprised 41.2%. Of 54
      STs observed only in one center, some STs played a locally significant role, like
      ST156 and ST393 in GI or ST372 and ST398 in TA. Among 16 new STs, five arose from
      evolution within the ST10 and ST131 clonal complexes. ESBLs and AmpCs accounted
      for 94.7% and 5.6% of the ESC-hydrolyzing beta-lactamases, respectively, being
      dominated by the CTX-M-like enzymes (79.9%), followed by the SHV (13.5%) and CMY
      2 (5.3%) types. CTX-M-15 was the most prevalent beta-lactamase overall (40.6%);
      other ubiquitous enzymes were CTX-M-14 and CMY-2. Almost none of the common
      clones correlated strictly with one beta-lactamase; although 58.7% of ST131
      isolates produced CTX-M-15, the clone also expressed nine other enzymes. A number
      of clone variants with specific pulsed-field gel electrophoresis and ESBL types
      were spread in some locales, potentially representing newly emerging E. coli
      epidemic strains.

PMID- 23114777
TI  - Biochemical characterization of cardiolipin synthase mutations associated with
      daptomycin resistance in enterococci.
AB  - Daptomycin (DAP) resistance in enterococci has been linked to mutations in genes
      that alter the cell envelope stress response (CESR) (liaFSR) and changes in
      enzymes that directly affect phospholipid homeostasis, and these changes may
      alter membrane composition, such as that of cardiolipin synthase (Cls). While Cls
      substitutions are observed in response to DAP therapy, the effect of these
      mutations on Cls activity remains obscure. We have expressed, purified, and
      characterized Cls enzymes from both Enterococcus faecium S447 (residues 52 to
      482; Cls447a) and Enterococcus faecalis S613 (residues 53 to 483; Cls613a) as
      well as Cls variants harboring a single-amino-acid change derived from DAP
      resistant isolates of E. faecium. E. faecium Cls447a and E. faecalis Cls613a are
      tightly associated with the membrane and copurify with their substrate,
      phosphatidylglycerol (PG), and product, cardiolipin (CL). The amount of PG that
      copurifies with Cls is in molar excess to protein, suggesting that the enzyme
      localizes to PG-rich membrane regions. Both Cls447a(H215R) and Cls447a(R218Q)
      showed an increase in V(max) (MUM CL/min/MUM protein) from 0.16 +/- 0.01 to 0.26
      +/- 0.02 and 0.26 +/- 0.04, respectively, indicating that mutations associated
      with adaptation to DAP increase Cls activity. Modeling of Cls447a to Streptomyces
      sp. phospholipase D indicates that the adaptive mutations Cls447a(H215R) and
      Cls447a(R218Q) are proximal to the phospholipase domain 1 (PLD1) active site and
      near the putative nucleophile H217. As mutations to Cls are part of a larger
      genomic adaptation process, increased Cls activity is likely to be highly
      epistatic with other changes to facilitate DAP resistance.

PMID- 23114778
TI  - Pharmacokinetics and pharmacodynamics of anidulafungin for experimental Candida
      endophthalmitis: insights into the utility of echinocandins for treatment of a
      potentially sight-threatening infection.
AB  - Candida chorioretinitis and endophthalmitis are relatively common manifestations
      of disseminated candidiasis. Anidulafungin is increasingly used for the treatment
      of disseminated candidiasis, but its efficacy for Candida endophthalmitis is not
      known. A nonneutropenic model of hematogenous Candida endophthalmitis was used.
      Anidulafungin at 5, 10, and 20 mg/kg was initiated at 48 h postinoculation. The
      fungal densities in the kidney and vitreous humor were determined. Anidulafungin
      concentrations in the plasma and vitreous humor were measured using high
      performance liquid chromatography (HPLC). A pharmacokinetic-pharmacodynamic model
      was used to link anidulafungin concentrations with the observed antifungal
      effect. The area under the concentration-time curve (AUC) associated with stasis
      was determined in the both the kidney and the vitreous humor. The results were
      bridged to humans to identify likely dosages that are associated with significant
      antifungal activity within the eye. Inoculation of Candida albicans resulted in
      logarithmic growth in both the vitreous humor and the kidney. The
      pharmacokinetics of anidulafungin were linear. There was dose-dependent
      penetration of the anidulafungin into the vitreous humor. The exposure-response
      relationships in the kidney and vitreous were completely discordant. AUCs of 270
      and 100 were required for stasis in the eye and kidney, respectively. The
      currently licensed regimen results in an AUC for an average patient that is
      associated with stasis in the kidney but minimal antifungal activity in the eye.
      We conclude that anidulafungin penetrates the eye in a dose-dependent manner and
      that dosages higher than those currently licensed are required to achieve
      significant antifungal activity in the eye.

PMID- 23114780
TI  - Antimicrobial properties of 8-hydroxyserrulat-14-en-19-oic acid for treatment of
      implant-associated infections.
AB  - Treatment options are limited for implant-associated infections (IAI) that are
      mainly caused by biofilm-forming staphylococci. We report here on the activity of
      the serrulatane compound 8-hydroxyserrulat-14-en-19-oic acid (EN4), a diterpene
      isolated from the Australian plant Eremophila neglecta. EN4 elicited
      antimicrobial activity toward various Gram-positive bacteria but not to Gram
      negative bacteria. It showed a similar bactericidal effect against logarithmic
      phase, stationary-phase, and adherent Staphylococcus epidermidis, as well as
      against methicillin-susceptible and methicillin-resistant S. aureus with MICs of
      25 to 50 MUg/ml and MBCs of 50 to 100 MUg/ml. The bactericidal activity of EN4
      was similar against S. epidermidis and its Deltaica mutant, which is unable to
      produce polysaccharide intercellular adhesin-mediated biofilm. In time-kill
      studies, EN4 exhibited a rapid and concentration-dependent killing of
      staphylococci, reducing bacterial counts by >3 log(10) CFU/ml within 5 min at
      concentrations of >50 MUg/ml. Investigation of the mode of action of EN4 revealed
      membranolytic properties and a general inhibition of macromolecular biosynthesis,
      suggesting a multitarget activity. In vitro-tested cytotoxicity on eukaryotic
      cells was time and concentration dependent in the range of the MBCs. EN4 was then
      tested in a mouse tissue cage model, where it showed neither bactericidal nor
      cytotoxic effects, indicating an inhibition of its activity. Inhibition assays
      revealed that this was caused by interactions with albumin. Overall, these
      findings suggest that, upon structural changes, EN4 might be a promising
      pharmacophore for the development of new antimicrobials to treat IAI.

PMID- 23114779
TI  - An improved small-molecule inhibitor of FtsZ with superior in vitro potency, drug
      like properties, and in vivo efficacy.
AB  - The bacterial cell division protein FtsZ is an attractive target for small
      molecule antibacterial drug discovery. Derivatives of 3-methoxybenzamide,
      including compound PC190723, have been reported to be potent and selective
      antistaphylococcal agents which exert their effects through the disruption of
      intracellular FtsZ function. Here, we report the further optimization of 3
      methoxybenzamide derivatives towards a drug candidate. The in vitro and in vivo
      characterization of a more advanced lead compound, designated compound 1, is
      described. Compound 1 was potently antibacterial, with an average MIC of 0.12
      MUg/ml against all staphylococcal species, including methicillin- and multidrug
      resistant Staphylococcus aureus and Staphylococcus epidermidis. Compound 1
      inhibited an S. aureus strain carrying the G196A mutation in FtsZ, which confers
      resistance to PC190723. Like PC190723, compound 1 acted on whole bacterial cells
      by blocking cytokinesis. No interactions between compound 1 and a diverse panel
      of antibiotics were measured in checkerboard experiments. Compound 1 displayed
      suitable in vitro pharmaceutical properties and a favorable in vivo
      pharmacokinetic profile following intravenous and oral administration, with a
      calculated bioavailability of 82.0% in mice. Compound 1 demonstrated efficacy in
      a murine model of systemic S. aureus infection and caused a significant decrease
      in the bacterial load in the thigh infection model. A greater reduction in the
      number of S. aureus cells recovered from infected thighs, equivalent to 3.68 log
      units, than in those recovered from controls was achieved using a succinate
      prodrug of compound 1, which was designated compound 2. In summary, optimized
      derivatives of 3-methoxybenzamide may yield a first-in-class FtsZ inhibitor for
      the treatment of antibiotic-resistant staphylococcal infections.

PMID- 23114781
TI  - Caspofungin kills Candida albicans by causing both cellular apoptosis and
      necrosis.
AB  - Caspofungin exerts candidacidal activity by inhibiting cell wall (1,3)-beta-d
      glucan synthesis. We investigated the physiologic mechanisms of caspofungin
      induced Candida albicans cell death. Apoptosis (programmed cell death) and
      necrosis were studied after C. albicans SC5314 cells were exposed to caspofungin
      at 0.06, 0.125, and 0.5 MUg/ml (0.5*, 1*, and 4* the MIC, respectively) for 3 h.
      Caspofungin at 0.125 and 0.5 MUg/ml reduced cellular viability by >50%, as
      measured by colony counts and methylene blue exclusion. Apoptosis and necrosis
      were demonstrated by annexin V and propidium iodide staining for
      phosphatidylserine externalization and loss of membrane integrity, respectively.
      At all concentrations of caspofungin, 20 to 25% and 5 to 7% of C. albicans cells
      exhibited early apoptosis and late apoptosis/necrosis, respectively (P value was
      not significant [NS]). Necrosis, on the other hand, was significantly greater at
      0.125 (43%) and 0.5 (48%) MUg/ml than at 0.06 MUg/ml (26%) (P values of 0.003 and
      0.003, respectively). The induction of apoptosis at concentrations less than or
      equal to the MIC was corroborated by dihydrorhodamine 123 (DHR-123) and
      dihydroethidium (DHE) staining (reactive oxygen species production), JC-1
      staining (mitochondrial membrane potential dissipation), and terminal
      deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and 4',6-diamidino-2
      phenylindole dihydrochloride (DAPI) staining (DNA damage and nuclear
      fragmentation). Moreover, electron microscopy of cells exposed to 0.125 MUg/ml of
      caspofungin showed hallmark apoptotic features like chromatin margination and
      condensation and nuclear blebs. Apoptosis was associated with metacaspase 1
      activation, as demonstrated by D2R staining. Caspofungin exerts activity against
      C. albicans by directly killing cells (resulting in necrosis) and causing others
      to undergo programmed cell death (apoptosis). Apoptosis is initiated at
      subinhibitory concentrations, suggesting that strategies to target this process
      may augment the benefits of antifungal agents.

PMID- 23114782
TI  - Functional analysis of pneumococcal drug efflux pumps associates the MATE DinF
      transporter with quinolone susceptibility.
AB  - The pneumococcal chromosome encodes about 140 transporters, many of which are
      predicted to be involved in efflux. In order to critically evaluate pneumococcal
      efflux, a series of transporter mutants were constructed, and their phenotypes
      were assayed by disk diffusion, microdilution drug susceptibility testing (MIC
      testing), growth of cultures at sub-MIC concentrations, and phenotype microarray
      analysis. Mutants with mutations in seven ATP binding cassette (ABC)
      transporters, three multiantimicrobial extrusion (MATE) family efflux pumps, and
      one major facilitator superfamily (MFS) transporter were obtained in
      Streptococcus pneumoniae strain DP1004. The susceptibility of these 11 mutants to
      over 250 different substances was compared to that of the parent strain. Of the
      tested transporters, only the ABC transporter PatAB (SP2073-5) presented a clear
      multidrug resistance (MDR) profile, as the mutant showed significantly increased
      susceptibility to ethidium bromide, acriflavine, and berberine. Among the other
      transporters analyzed, the mutants devoid of the MATE efflux pump SP2065
      exhibited reduced susceptibility to novobiocin, and those with mutations of the
      MATE family DinF transport system (SP1939) exhibited increased susceptibility to
      moxifloxacin, ciprofloxacin, and levofloxacin. This change in quinolone MIC was
      found to be independent from the competence-mediated effect of quinolones on the
      cinA-recA-dinF operon. Furthermore, the dinF mutant, in contrast to the parental
      strain, allowed selection for quinolone-resistant mutants when exposed to
      moxifloxacin. These data confirm the clear MDR profile of the PatAB ABC
      transporter and suggest for the MATE DinF a phenotype associated with quinolone
      susceptibility, particularly for moxifloxacin.

PMID- 23114784
TI  - Childhood and adult stressors and major depression risk: interpreting
      interactions with the sufficient-component cause model.
AB  - PURPOSE: Using a representative longitudinal cohort consisting of more than 8,000
      community residents, this study sought to evaluate patterns of interaction
      between childhood adversity and adult stressors in relation to MDE. The goal was
      to interpret the interactions using epidemiologic theory. METHODS: A Canadian
      longitudinal study called the National Population Health Survey (NPHS) was the
      data source. This NPHS began in 1994 and the cohort has subsequently been
      interviewed every 2 years. Childhood adversities were assessed retrospectively
      and adult stressors and MDE were evaluated during follow-up. Interactions between
      various potential MDE risk factors were assessed on an additive scale using
      linear regression and on a multiplicative scale using logistic regression.
      RESULTS: Hypothesized interactions between negative childhood experiences and
      more recent stressors were apparent in statistical models adopting an additive
      (linear regression), but not multiplicative (logisitic), perspective. According
      to the component-cause model of etiology, this pattern suggests shared causal
      mechanisms. There was no general tendency for such interactions to occur with
      other risk factors. CONCLUSIONS: Biological mechanisms responsible for early life
      calibration of stress response systems may generate persistent sensitization to
      stressors, thereby increasing the risk of MDE following exposure to stressful
      events later in life. Reliance on multiplicative models such as logistic
      regression and log-binomial regression in psychiatric epidemiological studies may
      render etiologically important interactions more difficult to identify.

PMID- 23114783
TI  - Cytostatic versus cytocidal activities of chloroquine analogues and inhibition of
      hemozoin crystal growth.
AB  - We report an improved, nonhazardous, high-throughput assay for in vitro
      quantification of antimalarial drug inhibition of beta-hematin (hemozoin)
      crystallization performed under conditions that are more physiological relative
      to previous assays. The assay uses the differential detergent solubility of
      crystalline and noncrystalline forms of heme and is optimized via the use of
      lipid catalyst. Using this assay, we quantify the effect of pH on the crystal
      growth-inhibitory activities of current quinoline antimalarials, evaluate the
      catalytic efficiencies of different lipids, and test for a possible correlation
      between hemozoin inhibition by drugs versus their antiplasmodial activity.
      Consistent with several previous reports, we found a good correlation between
      hemozoin inhibition potency versus cytostatic antiplasmodial potency (50%
      inhibitory concentration) for a series of chloroquine (CQ) analogues. However, we
      found no correlation between hemozoin inhibition potency and cytocidal
      antiplasmodial potency (50% lethal dose) for the same drugs, suggesting that
      cellular targets for these two layers of 4-aminoquinoline drug activity differ.
      This important concept is also explored further for QN and its stereoisomers in
      the accompanying paper (A. P. Gorka, K. S. Sherlach, A. C. de Dios, and P. D.
      Roepe, Antimicrob. Agents Chemother. 57:365-374, 2013).

PMID- 23114785
TI  - Lymphatic invasion identified with D2-40 immunostaining as a risk factor of nodal
      metastasis in T1 colorectal cancer.
AB  - BACKGROUND: The management of T1 colorectal cancer after local resection is
      controversial. Regional lymph node metastasis often occurs, requiring subsequent
      colonic resection. The aim of this study was to reevaluate the risk factors of
      nodal metastasis of T1 colorectal cancer, especially to examine lymphatic vessel
      invasion in serially prepared hematoxylin and eosin sections and D2-40
      immunostained sections to determine which is a better indicator of lymph node
      metastasis of T1 colorectal cancer. METHODS: The study investigated 120 patients
      who underwent bowel resection and were histologically diagnosed to have T1
      colorectal cancer in Kanagawa Cancer Center Hospital from 1995 to 2005. Serially
      prepared paraffin sections were stained with hematoxylin and eosin, or
      immunostained with D2-40 antibody or von Willebrand factor, and reevaluated for
      lymphatic vessel invasion and other risk factors, including venous invasion,
      histological grade, depth of submucosal invasion, and budding. RESULTS: Lymphatic
      invasion diagnosed with either hematoxylin and eosin staining (p = 0.022), or D2
      40 immunostaining (p = 0.001), and budding (p = 0.013) were significant risk
      factors for lymph node metastasis in the univariate analysis. Venous involvement,
      histological grade, or depth of submucosal invasion was not significant. The
      multivariate logistic regression analysis for the three risk factors found
      lymphatic invasion diagnosed with D2-40 as an independent risk factor (odds ratio
      6.048, p = 0.018, CI 1.360-26.89). The sensitivity, specificity, positive
      predictive value, and negative predictive value were 58 %, 88 %, 35 %, and 95 %,
      respectively. CONCLUSIONS: Lymphatic vessel invasion diagnosed with D2-40 was a
      better indicator to evaluate the risk for lymph node metastasis by T1 colorectal
      cancer.

PMID- 23114786
TI  - Efficacy and safety of temsirolimus in Japanese patients with metastatic renal
      cell carcinoma on hemodialysis.
AB  - BACKGROUND: We retrospectively investigated the efficacy and safety of
      temsirolimus, an inhibitor of the mammalian target of rapamycin, in patients with
      metastatic renal cell carcinoma (mRCC) on hemodialysis (HD). METHODS: This study
      included ten HD patients who were diagnosed with mRCC following radical
      nephrectomy and subsequently treated with temsirolimus between December 2010 and
      June 2012. Medical records of these patients were reviewed to evaluate the
      response to temsirolimus and treatment-related toxicities. RESULTS: Baseline
      characteristics of the patients are as follows: median age was 61 years, five
      patients had a Karnofsky performance status of <=80, and two, six, and two
      patients were classified into favorable, intermediate, and poor risk group,
      respectively, according to the Memorial Sloan-Kettering Cancer Center risk model.
      Initially, all patients received 25 mg intravenous temsirolimus weekly; however,
      dose modification was necessary in four patients, resulting in a relative dose
      intensity of 89.5 % throughout this study. All patients, except for one with
      progressive disease, were judged to have stable disease following treatment with
      temsirolimus. Six patients are still under treatment with temsirolimus, whereas
      four have stopped receiving temsirolimus because of the occurrence of progressive
      disease in three and that of adverse events (AEs) in one. Although all patients
      experienced AEs related to temsirolimus, severe AEs corresponding to >= grade 3
      occurred in only four, including thrombocytopenia in two, anemia in one, and
      asthenia in one. CONCLUSIONS: Treatment with temsirolimus is well tolerated and
      could provide comparatively favorable cancer control in Japanese mRCC patients
      undergoing HD.

PMID- 23114787
TI  - Solid pseudopapillary neoplasms of the pancreas: an 18-year experience at a
      single Japanese Institution.
AB  - PURPOSE: This study investigated the clinicopathological features and surgical
      management of solid pseudopapillary neoplasms at a single institution in Japan.
      METHODS: Seventeen patients (the largest series in Japan) those underwent surgery
      for pathologically confirmed solid pseudopapillary neoplasms were retrospectively
      reviewed. RESULTS: Sixteen patients were women and their mean age was 34.1 years.
      Most patients were asymptomatic (n = 11), and the average tumor diameter was 51.8
      mm. The most common imaging characteristic was tumors of solid and cystic type (n
      = 10), which were most commonly located in the pancreatic body (n = 7). All
      patients underwent surgical exploration, i.e., distal pancreatectomies in 7
      patients (laparoscopically performed in 2); middle pancreatectomies, 4;
      pancreaticoduodenectomies, 4; enucleation, 1; and liver resection, 1. No surgical
      mortalities occurred, and postsurgical complications occurred in 9 patients. Four
      patients had malignant tumors. One patient with liver metastases experienced
      recurrence, which was well controlled by paclitaxel. The remaining patients were
      disease free at a median follow-up of 51 months. CONCLUSIONS: Solid
      pseudopapillary neoplasms can be treated by complete tumor resection with limited
      resection or a minimally invasive approach when applicable. The combination of
      surgical resection and chemotherapy may therefore prolong survival, even in
      malignant cases.

PMID- 23114788
TI  - Immediate reconstruction using a modified inframammary adipofascial flap after
      partial mastectomy.
AB  - Breast conservative therapy (BCT) as treatment for early breast cancer usually
      ensures local control and acceptable cosmetic results. We describe a new
      technique of using an inframammary adipofascial flap to reconstruct defects
      caused by lower-pole partial mastectomy, which achieved excellent results (Kijima
      et al. in Am J Surg 193:789-91 (1); Sakai et al. in Ann Plast Surg 29(2):173-7,
      2; Ogawa Am J Surg 193:514-8, 3). We developed this procedure as an oncoplastic
      technique for a Japanese woman with a similar defect without ptosis. After
      partial mastectomy, the superior half of the flap is harvested via an initial
      incision along the inframammary line, and the inferior half is harvested via an
      additional incision along the caudal edge of the flap, to produce a crescent of
      de-epithelialized skin. A tongue-shaped flap containing the crescent of de
      epithelialized skin, subcutaneous fat, and the fascia of the vertical rectus
      abdominis muscle is then rotated upwards, gathered, and inserted into the breast
      defect.

PMID- 23114790
TI  - Exosomes: cell garbage can, therapeutic carrier, or trojan horse?

PMID- 23114791
TI  - Ternary Pd2/PtFe networks supported by 3D graphene for efficient and durable
      electrooxidation of formic acid.
AB  - A newly-designed network of ternary Pd(2)/PtFe nanowires on a three-dimensional
      graphene framework has been fabricated via a dual solvothermal approach, which
      presents superior electrocatalytic activity towards the oxidation of formic acid.

PMID- 23114789
TI  - Exosomes mediate the cytoprotective action of mesenchymal stromal cells on
      hypoxia-induced pulmonary hypertension.
AB  - BACKGROUND: Hypoxia induces an inflammatory response in the lung manifested by
      alternative activation of macrophages with elevation of proinflammatory mediators
      that are critical for the later development of hypoxic pulmonary hypertension.
      Mesenchymal stromal cell transplantation inhibits lung inflammation, vascular
      remodeling, and right heart failure and reverses hypoxic pulmonary hypertension
      in experimental models of disease. In this study, we aimed to investigate the
      paracrine mechanisms by which mesenchymal stromal cells are protective in hypoxic
      pulmonary hypertension. METHODS AND RESULTS: We fractionated mouse mesenchymal
      stromal cell-conditioned media to identify the biologically active component
      affecting in vivo hypoxic signaling and determined that exosomes, secreted
      membrane microvesicles, suppressed the hypoxic pulmonary influx of macrophages
      and the induction of proinflammatory and proproliferative mediators, including
      monocyte chemoattractant protein-1 and hypoxia-inducible mitogenic factor, in the
      murine model of hypoxic pulmonary hypertension. Intravenous delivery of
      mesenchymal stromal cell-derived exosomes (MEX) inhibited vascular remodeling and
      hypoxic pulmonary hypertension, whereas MEX-depleted media or fibroblast-derived
      exosomes had no effect. MEX suppressed the hypoxic activation of signal
      transducer and activator of transcription 3 (STAT3) and the upregulation of the
      miR-17 superfamily of microRNA clusters, whereas it increased lung levels of miR
      204, a key microRNA, the expression of which is decreased in human pulmonary
      hypertension. MEX produced by human umbilical cord mesenchymal stromal cells
      inhibited STAT3 signaling in isolated human pulmonary artery endothelial cells,
      demonstrating a direct effect of MEX on hypoxic vascular cells. CONCLUSION: This
      study indicates that MEX exert a pleiotropic protective effect on the lung and
      inhibit pulmonary hypertension through suppression of hyperproliferative
      pathways, including STAT3-mediated signaling induced by hypoxia.

PMID- 23114792
TI  - The effect of hemodialysis on liver stiffness measurement:  a single-center
      series.
AB  - BACKGROUND/AIMS: The noninvasive measurement of liver stiffness using transient
      elastography (TE) is increasingly being used alongside liver biopsy. However,
      several conditions may lead to higher liver stiffness values without reflecting
      more fibrosis. Such conditions (e.g. hepatitis, cholestasis, heart failure,
      mechanical ventilation) limit the interpretation of liver stiffness measurements.
      The influence of hemodialysis on the measurement of liver stiffness has not been
      investigated to date. Here, we analyzed liver stiffness assessed by fibroscan in
      17 patients directly before and after a hemodialysis session. PATIENTS AND
      METHODS: Measurement of hepatic stiffness by TE was carried out using the
      Fibroscan device with the 'M probe' directly before and directly after one
      session of hemodialysis. Each measurement consisted of at least 10 individual and
      valid measurements, with a success rate of at least 60%, and an interquartile
      range of less than 25%. All measurements were carried out by one investigator not
      involved in patient management. RESULTS: Before dialysis, the median TE was 5.1
      kPa (2.8-17 kPa). Ten patients had values below the threshold of 7.1 kPa and
      seven patients had TE>7.1 kPa. The median net fluid withdrawal by hemodialysis
      was 2.5 l (0.4-3.1 l) and did not differ between patients. After dialysis, the TE
      median was 7.4 kPa (3.5-12.5 kPa) and had changed in all patients except one.
      Liver stiffness increased significantly when the initial TE was lower than 7.1
      kPa (P=0.05), but not when the initial TE was higher than 7.1 kPa. Furthermore,
      the magnitude of the change in TE after hemodialysis correlated inversely with
      the liver stiffness before hemodialysis (P=0.03) and with spleen length measured
      by ultrasound (P=0.03). CONCLUSION: This study is the first to report on the
      influence of hemodialysis on liver stiffness measurement. In contrast to previous
      reports, liver stiffness might increase after fluid withdrawal if patients do not
      show significant fibrosis. We conclude that before dialysis, TE possibly better
      differentiates between patients with or without significant fibrosis.

PMID- 23114793
TI  - Increase in skeletal-muscle glycogenolysis and perceived exertion with
      progressive dehydration during cycling in hydrated men.
AB  - This study investigated the effects of progressive mild dehydration during
      cycling on whole-body substrate oxidation and skeletal-muscle metabolism in
      recreationally active men. Subjects (N = 9) cycled for 120 min at ~65% peak
      oxygen uptake (VO2peak 22.7  degrees C, 32% relative humidity) with water to
      replace sweat losses (HYD) or without fluid (DEH). Blood samples were taken at
      rest and every 20 min, and muscle biopsies were taken at rest and at 40, 80, and
      120 min of exercise. Subjects lost 0.8%, 1.8%, and 2.7% body mass (BM) after 40,
      80, and 120 min of cycling in the DEH trial while sweat loss was not
      significantly different between trials. Heart rate was greater in the DEH trial
      from 60 to 120 min, and core temperature was greater from 75 to 120 min. Rating
      of perceived exertion was higher in the DEH trial from 30 to 120 min. There were
      no differences in VO2, respiratory-exchange ratio, total carbohydrate (CHO)
      oxidation (HYD 312 +/- 9 vs. DEH 307 +/- 10 g), or sweat rate between trials.
      Blood lactate was significantly greater in the DEH trial from 20 to 120 min with
      no difference in plasma free fatty acids or epinephrine. Glycogenolysis was
      significantly greater (24%) over the entire DEH vs. HYD trial (433 +/- 44 vs. 349
      +/- 27 mmol . kg-1 . dm-1). In conclusion, dehydration of <2% BM elevated
      physiological parameters and perceived exertion, as well as muscle
      glycogenolysis, during exercise without affecting whole-body CHO oxidation.

PMID- 23114794
TI  - Growing old with fibromyalgia: factors that predict physical function.
AB  - BACKGROUND: Fibromyalgia, a persistent, widespread pain condition, significantly
      limits physical function, threatening an older adult's health and ability to live
      independently. OBJECTIVES: The aim of the study was to identify predictors of
      physical function in older adults living with fibromyalgia and to examine the
      influence of resilience on the relationship between fibromyalgia pain and
      physical function. METHODS: This was a descriptive correlational, cross-sectional
      design using mailed questionnaires to analyze relationships between health
      related variables and physical function in a convenience sample of community
      dwelling older adults diagnosed with fibromyalgia (n = 224; age M = 62.1 years,
      SD = 6.75 years). Multiple regression was used to identify a priori predictors of
      physical function; hierarchical multiple regression was used to examine
      resilience as a moderator of pain and physical function. RESULTS: The sample was
      predominantly women, Caucasian, married, well educated, had moderate levels of
      income and tangible social support, and had low levels of physical function.
      Three-fourths were overweight or obese. Despite impaired physical function (Late
      Life Function and Disability Index, M = 51.5/100, SD = 9) and moderate levels of
      pain (Numeric Rating Scale, M = 5.47/10, SD = 2.6), resilience was moderately
      high (Resilience Scale, M = 137/175, SD = 20). An eight-variable disablement
      based model accounted for 48% of variance in physical function: age, income,
      education, depressive symptoms, body mass index, and physical activity accounted
      for 31%; pain added 14%; and resilience contributed an additional 3%. Resilience
      was not a moderator of fibromyalgia pain and physical function; resilience did
      contribute uniquely to physical function variance. DISCUSSION: Resilience, a
      novel variable in fibromyalgia research, was a unique predictor of physical
      function. Further research is needed to learn more about the relationships
      between resilience, fibromyalgia impact, and the aging process.

PMID- 23114795
TI  - Composite variables: when and how.
AB  - BACKGROUND: Use of composite variables is a common practice, but knowledge about
      what researchers should consider when creating composite variables is lacking.
      OBJECTIVE: The purpose of this paper was to present methods used to create
      composite variables with attention to advantages and disadvantages. METHODS:
      Methods of simple averaging, weighted averaging, and meaningful grouping to
      create composite variables are described briefly, and the context in which one
      method might be more suitable than the others is discussed. Study examples and
      comparisons of statistical power among these methods as well as Bonferroni
      correction are described. DISCUSSION: Each approach to creating composite
      variables has advantages and disadvantages that researchers should weigh
      carefully. With normally distributed data, composite variables provide the
      greatest increases in power when the original variables (that make up the
      composite variable) have similar associations with the outside outcome variable.

PMID- 23114796
TI  - Luminescence of Gd2(WO4)3:Ln3+ at ambient and high hydrostatic pressure.
AB  - This paper presents a spectroscopic characterization of Gd(2)(WO(4))(3):Ln(3+)
      (Ln=Eu, Pr, Tb and Dy). The luminescence and luminescence kinetics were measured
      under pressures up to 250 kbar. It was found that pressure quenches the
      luminescence of Pr(3+) and Tb(3+), whereas the emission of Eu(3+) and Dy(3+) was
      stable up to 250 kbar. This effect was related to a decrease in the ionization
      energy of Pr(3+) and Tb(3+) caused by pressure induced increase in energies of
      the Ln(2+) and Ln(3+) ions with respect to the band edges. Analysis of emission
      and excitation spectra allowed us to estimate the energies of the ground states
      of Ln(3+) and Ln(2+) with respect to the valence and conduction band edges of the
      Gd(2)(WO(4))(3) host. Differences between energies of the ground states of Ln(2+)
      and Ln(3+) have also been calculated.

PMID- 23114797
TI  - [Risk of bleeding and haemorrhagic complication with rivaroxaban--periprocedural
      management of haemostasis].
AB  - Rivaroxaban, the first direct factor-Xa inhibitor anticoagulant, has been
      approved for the prevention of venous thromboembolism in adult patients
      undergoing elective hip or knee replacement surgery, for stroke prophylaxis in
      patients with non-valvular atrial fibrillation and for the treatment of deep vein
      thrombosis. There is no requirement for coagulation monitoring with rivaroxaban
      in routine clinical practice. However, in certain clinical circumstances such as
      life-threatening bleeding or an emergency operation the measurement of the
      thromboplastin time with a sensitive reagent will deliver first information. A
      quantitative determination of rivaroxaban plasma concentration is possible using
      an anti-factor Xa assay. In the case of a patient under long-term anticoagulation
      with rivaroxaban requiring an elective surgery, a discontinuation of rivaroxaban
      20 to 30 hours before the operation is sufficient to normalize the associated
      bleeding risk, as long as the renal and liver function is normal. A longer
      interval should be taken into consideration, when the patient presents a renal
      and liver impairment or is of a higher age. In the event of an emergency
      operation effective rivaroxaban concentrations might be present. Nevertheless, we
      advise against using a prophylactic dose of factor concentrates. RECOMMENDATIONS:
      From a clinical perspective, in the event of a minor bleeding we recommend a
      temporary discontinuation of rivaroxaban, whereas for clinically relevant major
      or severe bleeding events a mechanical compression or a limited surgical i.e.
      interventional treatment is required. Supportive measures such as the
      administration of blood products or tranexamic acid might be beneficial. In
      addition to haemodynamic supportive measures life threatening bleeding events
      demand a comprehensive haemostasis management, as well as the application of PCC.

PMID- 23114798
TI  - [Dabigatran therapy--perioperative management and interpretation of coagulation
      tests].
AB  - Dabigatran, an oral, reversible direct factor IIa inhibitor, is approved in
      Europe for stroke prevention in atrial fibrillation and for the prevention of
      venous thromboembolism after elective hip and knee replacement. In contrast to
      vitamin K antagonists, a routine coagulation monitoring during the treatment with
      dabigatran etexilate is not necessary. However, in specific clinical situations
      such as invasive emergency procedures or serious haemorrhage, the actual
      anticoagulant status of dabigatran may be of importance for the treating
      clinician and can be assessed by clotting tests (aPTT, TT, ECT). The diluted
      thrombin time test (Hemoclot(r)), which is specifically calibrated for
      dabigatran, is useful for quantitative determination of the dabigatran serum
      concentration. In general, discontinuation of dabigatran etexilate 24 hours
      before standard elective surgery is sufficient to normalise the bleeding risk in
      patients with normal renal function. In patients with renal impairment and/or in
      the case of a high bleeding risk procedure the recommended duration of
      discontinuation is prolonged. If a bleeding episode occurs in a patient on
      dabigatran, further treatment should be based on the severity and localisation of
      the bleeding. A distinct feature of dabigatran is the possibility of effectively
      removing dabigatran from the circulation by haemodialysis. RECOMMENDATION: In the
      case of clinically minor bleedings, a delay in the administration of the next
      dabigatran etexilate dose is recommended. The length of the delay is based on the
      patient's individual thromboembolic risk. In minor bleedings the use of
      prothrombin complex concentrates is not indicated. In the case of moderate or
      major bleedings the main focus should be on stabilising the circulation by using
      fluids and blood products and, if a lesion can be identified, the local treatment
      thereof. If time and infrastructure is available, dialysis offers an effective
      and fast option to remove dabigatran out of the circulation. In the incidence of
      severe and life threatening bleedings, an additional, more complex haemostasis
      management is required. Besides haemodynamic stabilisation of the circulation,
      administration of prothrombin complex concentrates should not be delayed. It has
      to be kept in mind that standard laboratory coagulation parameters may not
      accurately reflect the effect of prothrombin complex concentrates in patients on
      dabigatran. Hence the effect of the prothrombin complex concentrate should be
      monitored clinically and adjusted by means of onset of coagulation in vivo.

PMID- 23114799
TI  - Erythrocytosis as a cause of false increase in prothrombin time and activated
      partial thromboplastin time.

PMID- 23114800
TI  - Secular and postsecular psychiatry.
AB  - Religious method of treatment dominated treatments of psychiatric patients until
      the start of twentieth century. After psychiatry was recognized as a distinct
      medical discipline, in nineteenth century, it begun to shift away from religious
      approach to the treatment of mentally ill persons.  During the twentieth century,
      it was enriched using psychotherapy, socio-therapy and biological methods of
      treatment, and completely secularized. The renaissance of religion and religious
      influence on secular events in the beginning of 21th century and postsecular
      atmosphere has launched a process of desecularization of psychiatry. It can best
      be seen through the changes in attitude towards spiritual and religious in the
      process of patients' evaluation, quality of life assessment, respect for the
      spiritual needs of patients in the process of clinical treatment, and objective
      consideration of the phenomenon of religiosity by psychiatrists and other mental
      health professionals. Without the ambition to precisely explain and define this
      notion, the basic sketch of what a postsecular psychiatry is and what it is not
      will be outlined in this paper. The goal is to open a professional debate over
      the issue, which would contribute that psychiatry, despite the ongoing challenges
      and provocations, maintains its essence as a medical discipline and adequately
      respond to all the needs of its patients, including those related to spirituality
      and religion. Overcoming rigid secular framework, psychiatry becomes more human
      and more close to human. In this way, psychiatry does not lose its "scientific
      component" because the effects of spirituality, beliefs or religious practices on
      mental health can be scientifically investigated without crossing the boundaries
      between the natural and spiritual sciences. Although people often consider that
      science and religion contradict each other, these are by their very nature
      convergently moving towards the meeting point even if it is located at infinity.

PMID- 23114801
TI  - Psychiatry at crossroad between crisis and new identity.
AB  - BACKGROUND: The question of identity of psychiatry as a medical profession as
      well as of the future of psychiatry has been the subject of much controversial
      discussion. METHOD: An overview of available literature on crisis and challenges
      in contemporary psychiatry as well as on future of psychiatry. RESULTS: In this
      paper we present our transdisciplinary multiperspective view on psychiatry based
      on the seven perspective explanatory approaches, on the art and practice of the
      learning organization as well as on the method of multiple working hypotheses.
      CONCLUSION: Conflict between our current knowledge and various concepts and
      schools in psychiatry will probably bring with itself a new scientific paradigm
      with new diagnostic phenotypes and refining the old ones. Psychiatry has the
      historical opportunity to shape the future of mental health care, medicine, and
      society.

PMID- 23114802
TI  - Environment and mental health.
AB  - Environments seen as the physical, chemical, and biological conditions to which
      organisms are subjected, define the ways we obtain various resources, their
      quantity and their quality. In interplay with our organisms, environments
      determine how 'fit' we are. An aspect of that fitness is the quality of mental
      functioning. Although there is a traditional view that there is something like an
      'objective environment' and an 'effective environment', a part of the objective
      environment that actually affects the organism, the dividing line between the two
      is rather obscure. Environment in general cannot be defined without taking into
      account the behaviour of the organism, and it is especially challenging to define
      what environment means to humans, given the enormous variation and scope of human
      behaviours; what it is that we require and tolerate. Simultaneously, that
      physical environment is the broader context of what we usually term 'social
      environment'. This paper outlines the conceptual problems in determining and
      evaluating the relationship between environmental conditions and more proximal
      determinants of mental health, at the same time reviewing the assumptions of some
      of the well-known examples of that relationship.

PMID- 23114803
TI  - Trauma, resiliency and recovery in children: lessons from the field.
AB  - War atrocities, natural disasters, community violence, physical abuse and
      catastrophic illnesses are many faces of trauma and are endemic and the children
      are the most vulnerable victims. Since 1994, this author has visited war zones
      and disaster areas 80 times in 18 different countries and has collected data on
      children's reactions across cultures. Most children around the world show similar
      responses to the exposure to traumatic experience. Sleep disturbance, nightmares,
      flashbacks and re-enactment of traumatic events are common. Most children recover
      from these symptoms in couple of weeks depending on the resiliency and
      vulnerability factors that they may or may not possess. This author also studied
      resiliency in children across cultures. In this presentation, the author will
      present the current understanding of PTSD including the role of amygdala, medial
      prefrontal cortex and hippocampus in symptom formation. Drawing from the lessons
      learned during his work with children around the world, the author will discuss
      the role of resiliency in recovery from trauma.

PMID- 23114804
TI  - Improving mental health in young people.
AB  - The gap between unmet need and access to care for mental ill-health is wider for
      adolescents and young people aged 12-25 years than any other age group worldwide.
      This age group is the peak time of onset for many mental disorders including
      mood, substance abuse and psychotic disorders. Effective interventions in primary
      or specialist care are likely to be most cost-effective at this age. Yet in most
      countries there are few opportunities for young people and their families to gain
      access to treatment and care for mental ill-health and preventive interventions.
      This is especially important for young people exposed to trauma and adversity.
      Few countries give sufficient attention to safeguarding and improving the mental
      health of young people and few have developed policies and programs to support
      this.  Policy and practice changes suitable for each country have two essential
      starting points: improved understanding of youth mental health within
      communities; and involving young people and their families in decisions that
      affect them. Using information technology to assist care is another desirable
      feature of modern service development suitable for any environment.  New
      directions and models of care to respond to better awareness and help-seeking and
      new approaches to health promotion are being developed in several countries, and
      psychiatrists have a central role in supporting these developments.

PMID- 23114805
TI  - Recovery--reshaping our clinical and scientific responsibilities.
AB  - CONTEXT: Advocacy for Recovery has been joined by research offering new
      perspectives on mental health policy, treatment, rehabilitation and anti
      discrimination efforts. OBJECTIVES: Chances and challenges of a Recovery model
      for the mental health field will be presented and discussed. KEY MESSAGES:
      Recovery is currently widely endorsed as a guiding principle of mental health
      policy. New rules for services, e.g. user involvement and person-centred care, as
      well as new tools for clinical collaborations, e.g. shared decision making and
      psychiatric advance directives, are being complemented by new proposals regarding
      more ethically consistent anti-discrimination and involuntary treatment
      legislation as well as participatory approaches to evidence-based medicine and
      policy. Recovery advocacy has been joined by research on recovery and resilience
      resulting in new data on the long-term perspectives of people experiencing common
      as well as severe mental health problems. Definitions of remission and recovery
      as well as the concept of chronicity are under debate. Research questions
      regarding recovery as a process as well as an outcome warrant scientific efforts
      enabling the integration of different perspectives as well as different
      methodologies. CONCLUSIONS: Consequences and challenges of the Recovery model
      need to be tackled from different perspectives by clinicians, researchers, policy
      makers and - essentially - users and carers and their representatives in order to
      be fully explored and brought to life.

PMID- 23114806
TI  - Impact of destruction of classic moral principles on ethical questions in
      psychiatry.
AB  - Society's treatment of psychiatric patients was always a reflection of social
      development and social awareness, as well as of ethical principles dominating a
      certain time period in that society. Over the last two and a half millennia,
      during which principles of Hippocratic ethics applied, attitudes towards
      psychiatric patients, from an ethical and practical standpoint, were and still
      are controversial to say the least. During this period thousands of people with
      mental disorders were abused, tortured, or killed, all of this in accordance to
      the existing ethical and legislative norms (Malleus Maleficarum, eugenic laws of
      totalitarian regimes...). In the last forty years many international
      organizations and associations brought forth a number of resolutions and
      declarations warning of the position and of the rights of psychiatric patients
      and giving instructions on the humane, that is to say ethical, treatment of this
      category of patients. In almost all the western countries laws are passed to
      protect the rights of people with mental disorders. Thanks to this and maybe even
      more to the development of psychiatry as a medical and scientific profession, the
      position of those with mental disorders is improving. However, at the same time
      over the last 40 years we are witnesses to the destruction of the classic moral
      principles and the establishment of certain "new" ethics which put psychiatric
      patients at a disadvantage, only in a more subtle way then before. This is why it
      is important to reexamine many of the ethical questions in psychiatry in the
      context of present ethical controversy.

PMID- 23114807
TI  - Self-disorders and the experiential core of schizophrenia spectrum vulnerability.
AB  - An increasing amount of empirical studies demonstrates that anomalies of self
      experience (self-disorders) are characteristic of schizophrenia and related
      spectrum conditions, indicating that self-disorders (SDs) are likely to
      constitute important vulnerability phenotypes. On a clinical level, SDs are non
      psychotic alterations of subjective experience that include disturbances of self
      awareness (e.g., fading first-person perspective, waning sense of basic identity,
      depersonalization and hyperreflectivity), autopsychic disorders (e.g., thought
      pressure or block, perceptualization of mental stream and spatialization of
      thoughts), loss of common sense (e.g., perplexity), and existential alterations
      (e.g., solipsistic grandiosity). Such experiences, define essential aspects of
      the clinical expressions of schizophrenia lending psychopathological coherence to
      its spectrum manifestations. Furthermore the experiential nature of SDs makes
      them amenable to the patient's introspection which can be elicited in the
      dialogical context of the psychiatric interview with important implication for
      the therapeutic relation. The aim of this presentation is to illustrate the
      phenomenological core of these experiential anomalies, emphasizing their
      topicality for the exploration of vulnerability to schizophrenia spectrum
      conditions and their coherence with the overall clinical picture.

PMID- 23114808
TI  - Is acute and transient psychotic disorder (ATPD) mini schizophrenia? The evidence
      from phenomenology and epidemiology.
AB  - Acute and transient psychotic disorders (ATPD) first appeared in ICD-10 but
      classification of acute psychosis has a long historical tradition. The prevalence
      rate of these disorders varies from 3.9 to 9.6 per 100,000 populations.
      Systematic clinical information that would provide definitive guidance on the
      classification of acute psychotic disorders is not yet available. Moreover there
      is no evidence available to guide the treatment of these disorders. In absence of
      the reliable epidemiological information the ATPD is treated as a form of 'mini
      schizophrenia' as if the disorder is an attenuated form of schizophrenia. A
      systematic review of the literature on acute and transient psychosis was
      conducted and all studies on epidemiology and treatment of acute and transient
      psychosis were identified. The existing evidence suggested that ATPD has little
      relationship with schizophrenia. ATPD is diagnostically unstable over time.
      Various estimates suggest that about 1/3 of patients with baseline ATPD retained
      their diagnosis over 3-12 years, the most frequent re-diagnosis being bipolar
      disorder and not schizophrenia. There are important differences in the
      epidemiology of this disorder from schizophrenia. These include gender
      distribution (ATPD has preponderance of females while equal gender distribution
      is one of the most established finding in epidemiology of schizophrenia) and much
      better premorbid level of functioning and social interactions. Other
      distinguishing features include the age at onset (onset throughout adult life,
      but usually between the 30- 50 years), development, and duration of symptoms
      (ATPD have an acute or even abrupt onset and the onset is only rarely
      precipitated by acute severe stress) and usually a favourable outcome, in spite
      of the fact that they are frequently recurrent. Literature on the subject is
      scanty and has serious methodological limitations. Treating ATPD has serious long
      term implications for the care of those suffering from ATPD. Long term treatments
      with antipsychotics which can induce metabolic disorders and reduce life
      expectancy, amongst many other side effects mean that we have to reconsider our
      approach to the diagnosis of ATPD seriously. Treating the acute and transient
      psychosis as a mini schizophrenia is seriously hindering research and clinical
      practice. I will review the epidemiology and phenomenology of acute and transient
      psychotic disorder, the current gaps in knowledge and its effects on our clinical
      practice in the light of systematic review of the evidence.

PMID- 23114809
TI  - The issue of five year outcomes in early intervention in psychosis--consequences
      for the design of services.
AB  - Early intervention for psychosis services have been a very important area of
      development in Community Mental Health in recent years. Here we attempt to
      describe the general principles on which early intervention services are based,
      the interventions which such services carry out, and the expected outcomes
      according to the latest literature. While there is consensus that at 3 years
      after the first episode, outcomes from an ad hoc Early Intervention Team are
      better than treatment as usual in a Community Mental Health Team. It has been
      found in most studies, that if patients are treated in an Early Intervention Team
      for three years, and then transferred back to a Community Mental Health Team, the
      improvement in outcomes is lost. The reasons for this are described. The
      Implications for services are that, if outcomes are to be optimised in the
      treatment of schizophrenia, then assertive treatment in the community needs to be
      given for as long as possible.

PMID- 23114810
TI  - Frequency of bipolar affective disorder in patients with major depressive episode
      with or without psychiatric co-morbid disorders.
AB  - BACKGROUND: Epidemiological studies indicate that only 20% of patients with
      Bipolar Affective Disorder are diagnosed on time while in 35% of patients
      diagnosis is 10 years late. Unipolar depression represents the most frequent
      misdiagnosis. AIM: The aim of this study was to determine the frequency of BAD in
      subjects diagnosed with Major Depressive Episode with or without co-morbid
      disorders. SUBJECTS: The study was a part of a large international, multi-center,
      non-interventional study that was conducted in 14 countries between May and
      November 2008. Sample in Bosnia and Herzegovina included 200 adult subjects with
      MDE according to the DSM IV diagnostic criteria who consented to take part in the
      study, who did not exhibit symptoms of acute somatic condition at the time, and
      who were capable of filling the HCL-32 checklist. METHODS: The following
      assessment instruments were used: CRF (Case Report Form) that includes general
      psychiatric assessment, GAF (Global Assessment of Functioning) and HCL-32
      (Hypomania Symptom Checklist). RESULTS: Bipolar Affective Disorder was diagnosed
      in 67.84% of the study subjects, and MDE in 32.16%. At least one co-morbid
      psychiatric disorder was present in 77.78% of subjects with BAD and in 22.22% of
      subjects with MDE. Anxiety disorders co-morbidity was present in 61.9% of
      subjects with BAD and in 38.10% of subjects with MDE. CONCLUSIONS: Our results
      confirm previous research about underdiagnosing of BAD. This has unforeseen
      consequences on the course and prognosis of the disorder significantly affecting
      quality of life of the patients.

PMID- 23114811
TI  - Serotonergic organization of the central nervous system.
AB  - The last 50 years of researches of biochemism and the CNS functionality are
      intensively engaged in studying the role of monoamine neurotramsmitter serotonin
      (5-hydroxytryptamin) (5-HT). The serotonergic receptors function depends on spot
      where the receptor function, the dynamic relationship with other transmitters and
      stimulation that can activate or inhibit specific neurons. The results of
      research in biochemistry, neurophysiology and neuroradiology have provided
      insight into the complexity of the operation of key structures such as the
      amygdala, prefrontal cortex and hippocampus, whose role varies depending on the
      received external impulses and the impulses that are sent to relevant areas. This
      implies that the transmitters and especially 5-HT, have much wider effects that
      are determined not to structures but by the impulse dynamics. It also means that
      psychopharmaceutical drugs whose therapeutic effect is based on the change of the
      concentration of serotonin in the synapse and the postsynaptic receptors
      depending on where they operate, have an effect on affective or cognitive
      symptoms. Serotonergic antidepressants by changing the concentration of serotonin
      change primarily affective manifestations but also they have significant
      influence on all the spectrum of serotonergic disorders not only emotional, but
      also the cognitive level, which is also a confirmation that the therapeutic
      effects do not depend only on the simple change of serotonin concentration but
      also of the level where these changes occur in dynamic comparison of key
      transmitters. Atypical antipsychotics which have low affinity for dopaminergic
      and high affinity for serotonergic receptors are seen through the dynamic
      relationship of serotonin, dopamine and noradrenalin in nigrostriatal,
      mezocortical, mezolimbic and tuberoinfudibular pathways.

PMID- 23114812
TI  - Psychiatric disorders in neurology.
AB  - Psychiatric disorders (PDs) in neurology are more frequent then it verified in
      routine exam, not only in the less developed but also in large and very developed
      neurological departments. Furthermore, psychiatric symptoms (PSs) in neurological
      disorders (NDs) among primary health care physicians and other specialties are
      often neglected. Anxiety and depression are most common, but hallucinations,
      delusions, obsessive-compulsive disorder and delirium or confusional state are
      also frequent comorbidity in many neurological conditions such as stroke,
      epilepsy, multiple sclerosis (MS), Parkinson disease (PD). Depression and NDs
      also have a bidirectional relationship, as not only are patients, for example
      with stroke at greater risk of developing depression, but patients with
      depression have a two-fold greater risk of developing a stroke, even after
      controlling for other risk factors.  Dementia or cognitive impairment are part of
      clinical picture of PD, stroke patients, patients with MS, Huntington disease
      etc. The prototype of dementia in PD and other NDs is a dysexecutive syndrome
      with impaired attention, executive functions and secondarily impaired memory. So
      called "functional" (or psychogenic or hysterical/conversion) symptoms are
      relatively infrequent in "neurological" conditions, but very often unrecognized
      and not properly treated.  Treatment of PSs in neurology, basically are not
      different then treatment of these symptoms in psychiatry and should be include
      pharmacotherapy and psychiatry. This presentation gives an overview of frequency
      and type of PSs underlying necessity to recognize these disorders in every day
      routine exam and properly treatment.

PMID- 23114813
TI  - Neurobiology of suicidal behaviour.
AB  - It is known that suicidal behaviour has multiple causes. If triggers could be
      mainly attributed to environmental factors, predisposition could be associated
      with early stressors on one side such as childhood adversities and genetic
      predisposition. No convincing animal model of suicide has been produced to date.
      The study of endophenotypes has been proposed as a good strategy to overcome the
      methodological difficulties. However, research in suicidal behaviours using
      endophenotypes entrails important methodological problems. Further,
      serotoninergic system was studied in patients with suicidal behaviour primary due
      to its involvement of serotonin in impulsive-aggressive behaviour, which has been
      shown to be a major risk factor in suicidal behaviour. Not only on the level of
      neurotransmitters but also the regulation of neurotropic factors could be
      impaired in suicide victims. Multiple lines of evidence including studies of
      levels of BDNF in blood cells and plasma of suicidal patients, postmortem brain
      studies in suicidal subjects with or without depression, and genetic association
      studies linking BDNF to suicide suggest that suicidal behaviour may be associated
      with a decrease in BDNF functioning. It seems that especially specific gene
      variants regulating the serotoninergic system and other neuronal systems involved
      in stress response are associated with suicidal behaviour. Most genetic studies
      on suicidal behaviour have considered a small set of functional polymorphisms
      relevant mostly to monoaminergic neurotransmission. However, genes and epigenetic
      mechanisms involved in regulation of other factors such as BDNF seem to be even
      more relevant for further research.

PMID- 23114814
TI  - Antipsychotics--history of development and field of indication, new wine--old
      glassess.
AB  - More than half a century ago, Delay and colleagues have discovered, quite
      accidentally, that antihistamine (chlorpromazine) relieves psychotic symptoms.
      This discovery prompted further investigation through a series of performed
      experiments aimed to elucidate the antipsychotic mechanism of action. Initial
      results have shown that antipsychotic drugs in experimental animals lead to
      "neuroleptic effect" (indifference). However, not until the end of 1960s, it
      becomes clear that all previously known antipsychotics block dopamine receptors,
      particularly postsynaptic D2 receptors. The next three decades marked the
      development and application of these so-called classic neuroleptics in the
      treatment of psychotic patients. During the nineteen nineties, as a result of
      ongoing efforts to achieve greater efficiency and reduce the scope of side
      effects, novel antipsychotics were synthesized (second generation antipsychotics-
      SGA). As a result the notion of serotonin-dopamine antagonist (SDA) was
      formulated. According to one of the hypothesis, "new", so called atypical
      antipsychotic drugs strongly block the serotonin (5-HT2), and weakly block the
      dopamine (D2) receptors. Yet, there is still a debate as to the molecular basis
      of atypicality, whether it is in dopaminergic and serotonergic antagonism of
      neurotransmission or it lays exclusively in the modulation of dopaminergic system
      and dissociation rate at the level of D2 receptors in specific brain regions.
      Although the synthesis and use of antipsychotics in clinical practice have
      radically changed not only the basic approach to the patient, but also the
      quality of life of millions of people, the question remains whether this is just
      "old wine in new glasses".

PMID- 23114815
TI  - Psychotherapy in 21st century.
AB  - INTRODUCTION: Today, psychological processes and brain is no longer looked at as
      something less scientific in comparison with physical processes, so mental
      diseases will become equal as physical diseases very soon. Until recently, brain
      functioning could be observed only in patients with cerebral lesions, after
      surgery, and on animals, but it is possible today to observe it directly with
      modern imaging techniques. AIM: The aim of this presentation is to point out that
      optimal health and functioning, which are basic assumptions of both neuroscience
      and psychotherapy is related to increased level of integrity and neural networks
      growth. METHODS: Therefore, neurological development can be seen as development
      determined by experience. More neural networks will be developed during critical
      periods then, ultimately, will be used. Environment in which child lives and
      develops determines which networks are going to live through, and those that were
      not stimulated are susceptible for neural extinction (pruning). Quality of
      parental relationship has basic impact on brain development. Mother's capacity to
      regulate newborn's affects is directly linked to future child's capacity to
      regulate his/her own affects. RESULTS: Positive experiences from an early
      childhood, together with positive genetic heritage, ensure proper brain
      development. First years in human life are also a period of most turbulent brain
      development, and those early experiences have disproportionally large impact on
      human brain development. CONCLUSIONS: Brain growth and differentiation are not
      only determined genetically but also with constant interactions with environment.
      This epigenetic brain information doesn't end in an early childhood. There is a
      lifelong redistribution of cortical networks, depending on individual experience,
      including creation of de-novo generation of neurons in adult hippocampus, as
      recently proved, and neuroplasticity is precondition for any persisted behavioral
      change, behavior, cognition and emotion.

PMID- 23114816
TI  - Insight in psychotherapy.
AB  - The same as with many other psychoanalytic constructs, it took a long time to
      theoretically conceptualize "insight". Throughout decades, psychoanalysts and
      psychotherapists of various techniques, observed and detail discussed transcripts
      of sessions so to get an insight into what leads to a change in structure of
      patients during psychotherapeutic treatment. In this article, authors attempted
      to integrate all developmental achievements on insight in psychoanalytic
      literature and further on. It is apparent that there are numerous models which
      contribute to a change in structure of a patient. Additionally, an outline of few
      situations was given, as a part of therapeutic process which contributes to
      insight. The aim of this article is to give readers insight into how there is
      more than one process which leads to insight; it is a complex work and various
      methods can be used, by using conscious and unconscious ways to help patient
      achieve liberation from difficulties for which they seek help.

PMID- 23114817
TI  - Psychodynamic psychotherapy in psychiatry: the missing link?
AB  - Polarization of biological and psychosocial aspects of psychiatry determines the
      artificial division of the "biological" psychiatrists and psychiatrists
      "psychotherapists". This division resulted from a certain dose of mystification
      of the psychotherapeutic work of those practicing, and fear of psychological
      determinism of the functioning, of those who are looking for answers in the
      biological substrate. The gap of polarization is now described as a form of
      Cartesian dualism, the division of the mind and the brain. The integration of
      psychotherapy in psychiatry is the trend in psychiatric specialization, virtually
      erasing this dualism. This paper describes novelties related to psychotherapy
      training, as defined by the Section of Psychiatry within the European Union of
      Medical Specialities and the Psychiatry Residency Review Committee in the
      U.S.that provided guidelines for the psychotherapeutic competences of future
      psychiatrists. We are also describing the situation in Serbia, where there was a
      formal specialization in psychotherapy at the Medical Faculty in Belgrade, for
      over thirty years, and education in psychodynamics of adults, at the Mental
      Health Institute, from 1978 to 2007. In addition, there are a number of other
      schools of psychotherapy, providing training for psychiatrists. This framework
      allows the authors, based on their experience and previous research, to present
      their views concerning the future of training in psychodynamic psychotherapy in
      psychiatric education.

PMID- 23114818
TI  - Contemporary concepts of dissociation.
AB  - The concept of dissociation was developed in the late 19th century by Pierre
      Janet for conditions of "double consciousness" in hypnosis, hysteria, spirit
      possession and mediumship. He defined dissociation as a deficit in the capacity
      of integration of two or more different "systems of ideas and functions that
      constitute personality", and suggested that it can be related to a genetic
      component, to severe illness and fatigue, and particularly to experiencing
      adverse, potentially traumatizing events. By the late 20th century, various and
      often contradictory concepts of dissociation were suggested, which were either
      insufficient or exceedingly including when compared to the original idea.
      Currently, dissociation is used to describe a wide range of normal and abnormal
      phenomena as a process in which behaviour, thoughts and emotions can become
      separated one from another. A complete presentation of mechanisms involved in
      dissociation is still unknown. Scientific research on basic processes of
      dissociation is derived mainly from studies of hypnosis and post-traumatic stress
      disorder. Given the controversies in modern concepts of dissociation, some
      researchers and theorists suggest return to the original understanding of
      dissociation as a basic premise for the further development of the concept of
      dissociation.

PMID- 23114819
TI  - Posttraumatic stress disorder: paradigm for new psychiatry.
AB  - Although the description of the PTSD clinical picture dates from history, our
      professional community has known for about two decades. PTSD is clearly defined
      in the 10th International Classification of Diseases, World Health Organization
      and IV Diagnostic Statistical Manual of Mental Disorders. Together with panic
      disorder, agoraphobia, specific and social phobias, obsessive-compulsive disorder
      and generalized anxiety disorder is one of the large groups of anxiety disorders.
      A superficial approach, we could conclude that in the relation with PTSD is all
      clear. It was also found that PTSD is often associated with depression, anxiety
      disorders, and excessive drinking, substance abuse, and personality disorder,
      dissociative and other disorders.  It is true that our knowledge of PTSD from
      year to year is larger and larger. However, regarding PTSD, there are many
      uncertainties, doubts and controversies. Is PTSD a disorder, illness, rent or a
      passing phase in the development of various diseases? In recent years, there are
      many studies that are trying to illuminate different aspects of PTSD. Numerous
      clinical, neurobiological, psycho physiological and MR volumetric studies
      indicate many uncertainties related to PTSD. About psychotic PTSD is more
      frequently discussed and written. Whether PTSD is or its symptoms or
      complications during periods of decompensation may have the character of the
      psychosis and the psychosis within PTSD or a co-morbid diagnosis? It is certain
      that about PTSD there are many uncertainties and doubts, that the investigation
      should continue and that PTSD is a paradigm for new psychiatry.

PMID- 23114820
TI  - Changes in intellect area in war veterans with developed PTSD.
AB  - INTRODUCTION: The previous neuropsychological studies have pointed to a
      significant understanding of the neurobiological correlates of Post Traumatic
      Stress Disorder with deficits in the functions of the intellect. AIM: To
      establish the existence of intellectual changes in war veterans with developed
      PTSD and their relationship to PTSD. METHODS: War veterans are divided into two
      groups: Group A, war veterans with PTSD and "B" groups, veterans without PTSD.
      Were used: Wechsler's Adult Intelligence Scale (WB-F2); Trauma Questionnaire (UT
      PTSD); Questionnaire-socio-biographical data RESULTS: The severity of stress and
      severity of post-traumatic stress disorder is directly associated with the
      intellectual functions. War veterans, who had more severe traumatic experience,
      with a strong and destructive PTSD compared to veterans without PTSD had
      significantly lower ratio of general, verbal and non-verbal intelligence quotient
      of mental efficiency, a high level of mental deterioration with significantly
      pronounced oscillations in intratest and insidetest variability. Veterans with
      PTSD showed significantly lower scores in the immediate memory capacity,
      efficient attention, concentration under conditions of mental activity, visual
      perceptual skills predicted exactly bit of trivial things, of associative
      elasticity of thinking and short-term learning abilities. CONCLUSIONS: These
      results suggest that deficits in the intellect, are not primarily the result of
      low intelligence, of premorbid states, but it occurs under the devastating impact
      of PTSD, which influencing changes in certain centers in the brain and changes in
      intellectual functioning.

PMID- 23114821
TI  - Contemporary characteristics of the developmental age psychopathology.
AB  - At present time, it may seem that the available therapeutic possibilities and
      methods have resulted in lower prevalence, and even disappearance, of certain
      psychopathological entities. The advancement of therapeutic methods has made
      possible to tackle new issues that are emerging in developmental psychopathology.
      These issues are directly related to the specifics of the current social sphere,
      reflecting the turbulent social changes as consequences of globalization and
      economic instability in the world. Humanitarian crises are ever more often
      accompanied by increased prevalence of mental disorders and psychological
      distress of the population in general. Based on child psychiatrists' reports from
      all corners of the globe, it is evident that the features of developmental
      psychopathology are constantly changing. The research studies refer to social
      events and phenomena that in previous decades were not to be found at the fore of
      clinical entities distribution. Thus, there are research reports on personality
      disorders in developmental age. Some thirty years ago, opinions were still
      divided on whether or not there existed personality disorders in developmental
      age. Nowadays, however, it is an accepted fact among experts that these disorders
      in youth warrant attention. This prevailing view has instigated research in this
      domain and now projects are carried out in many countries, so it is safe to say
      that the research has become global. Furthermore, the researchers' pay much
      attention to the problem of suicide both in youth and in children. Some special
      areas of research are being identified, such as the suicide risk assessment in
      adolescents undergoing short term antidepressant therapy. Latest data show that
      researchers are more often engaged in parent education, teaching them behaviours
      they need to raise a child with hyperactivity syndrome. Also, research results on
      the quality of emotional relationship with adoptive parents have been published
      with increasing frequency, especially by American authors. The results show that
      social services are detecting more and more cases of abuse of adopted children.
      Psychosomatic illnesses and liaison therapy at paediatric wards also feature
      prominently in current psychopathology. They are followed by issues of mental
      health of populations in humanitarian crises, including war, hard physical labour
      and abuse of child labour. The presentation includes a brief overview of
      psychopathology from the local perspective, with latest examples from clinical
      practice. The presentation concludes with the constatation that peculiarities of
      child and adolescent psychopathology follow the dynamic corresponding to the
      global social changes and increasing economic problems.

PMID- 23114822
TI  - First-psychotic episode in childhood and adolescence.
AB  - INTRODUCTION: Psychosis in childhood and adolescence are defines as having
      delusions or hallucinations, with the hallucinations occurring in the absence of
      insight into their pathological nature. A broader definition includes symptoms
      such as disorganised speech and grossly disorganised or catatonic behavior.
      Negative symptoms such as alogia, amotivation and anhedonia can be present.
      Cognitive and mood symptoms may also be present. There are relatively few
      epidemiological studies on child and adolescent onset psychosis. It is generally
      held that the incidence of psychosis, and especially of schizophrenia, increases
      markedly during the teenage years, with a preponderance of male over female
      patients. AIM: This is a descriptive review of child and adolescents with
      psychotic symptoms. It aims to describe their clinical profile, associated risk
      factors and management strategies utilised. RESULTS: While psychotic disorders
      are considered rare in children and adolescents, they may severely affect
      development and long-term functioning. Early identification and intervention are
      critical to improving outcome. This review suggests that a considerable number of
      adolescents presenting with psychosis required lengthy periods of inpatient care.
      CONCLUSION: There is often diagnostic uncertainty in the first episode of child
      and adolescent-onset psychosis. Key diagnostic issues relate to distinguishing
      schizophrenia from bipolar disorder in psychotic adolescents. The differential
      diagnosis may include psychotic disorder due to a general medical condition, or a
      substance-induced psychotic disorder.

PMID- 23114823
TI  - Treatment of addicts in Bosnia and Herzegovina--constraints and opportunities.
AB  - Chronology of important historical events in Bosnia and Herzegovina during past
      two centuries indirectly influenced the incidence and prevalence of different
      psychoactive substances use and thus the organization of services for the
      treatment of persons who develop addiction symptoms. The organization of health
      system in the last war, 1992-1995, suffered enormous damage and the reform
      process which inevitably followed, included the area of mental health care
      services and the establishment of network of centers for mental health in the
      community (CMHC). The centers are functioning within the primary health care
      almost in whole country, with specialized centers for the prevention and
      treatment of addicts and the therapeutic communities, which today represents the
      basic organizational units to help people who have drug related issues. In this
      paper we will present the possibility of treatment of drug addicts in Bosnia and
      Herzegovina, from consulting services, psycho-education and early detection of
      disease, detoxification and substitution programs with Methadone and Suboxone, as
      well as programs of rehabilitation and resocialization. Although a very
      complicated political and administrative structure of the country, insufficient
      financial support, pronounced stigmatization of addicts, insufficient staffing
      and number of treatment centers are objective obstacles for progress in treatment
      of addicts, we believe that, with existing resources, these constraints can be
      converted into new opportunities in terms of improvement of treatment options in
      the future.

PMID- 23114824
TI  - Medically assisted treatment for opiate addiction--suboxone method as prevention
      of social exclusion of youth--Tuzla model.
AB  - AIM: To present medically assisted treatment for opiate addiction with
      substitution medicament Suboxone and prevention of social exclusion of young
      opiate addicts in Bosnia and Herzegovina. GENERAL OVERVIEW: Until recently there
      was no solution for long-term and comprehensive treatment of young persons who
      suffer from opiate addiction. This is not an illness that impairs only
      psychological and physical health of addicts with possible fatal aftermaths, but
      serious societal problem due to its consequences such as delinquency, crimes and
      violence that lead young people to social exclusion. There are no capacities
      within the existing health facilities for long-term stationary treatment, which
      is necessary for drug addiction. In addition, far less adequate solution is
      placement of young addicts into penal and correctional institutions, which are
      stigmatizing and contribute to their exclusion from normal social life.  Hence,
      the latest medically assisted method of substitution treatment with a combination
      of buprenorphine and naloxone (Suboxone) is introduced. This medicament, with its
      characteristics, offers possibility for outpatient treatment, and prompt and
      effective results of detoxification and weaning of opiates is to be achieved.
      Opiate addicts that undergo this treatment benefit from "clear mind" and
      capability for occupational and social activities, which significantly improves
      the quality of their family and social relations. With Suboxone substitution
      method, the institutional (inpatient) treatment is to be avoided and social
      exclusion of young addicts treated with Suboxone prevented. CONCLUSION: Medically
      assisted treatment for opiate addiction with Suboxone is conducted in outpatient
      setting with the involvement of close relatives who are not addicted. It brings
      back "clear mind" to previous addicts, does not stigmatize but contribute to re
      socialization and prevention of social exclusion of young opiate addicts.

PMID- 23114825
TI  - The Psychiatric Association of Bosnia-Herzegovina--distinctive role in national
      and international framework.
AB  - BACKGROUND: Following the initiative and after preparation that lasted about a
      year, a national association of experts dealing with psychiatry has been formed
      in our country named Psychiatric Association of Bosnia-Herzegovina (PABH). On
      March 17th 2008 PABH was formally started with its work that would be since 2009
      been actively promoted and profiling as one of the best organized professional
      associations in B-H. Recognition on the international level and the active role
      of the PABH were substantially achieved in 2010 in the World (WPA), and from 2011
      in European (EPA) Psychiatric Association. The Third Congress of Psychiatrists of
      B-H with International participation is the first in a series of future
      Congresses organized by PABH. METHODS: This retrospective review describes the
      development and significance of the PABH both nationally and internationally
      through the documentation and archives of the PABH. RESULTS: The PABH is included
      in major psychiatric events in the country (active participation in the
      organization, logistics and scientific programme) and experts from our country
      are involved in an increasing number of international professional bodies.
      CONCLUSIONS: The PABH is the leading psychiatric association B-H, an active
      member of the largest and most important international organizations, with a
      continuous increase of the number of members who recognize the importance,
      relevance and quality of the PABH and further progress in its development and
      tendencies to harmonize psychiatric practice in the country and internationally.

PMID- 23114826
TI  - Microfluidic artificial "vessels" for dynamic mechanical stimulation of
      mesenchymal stem cells.
AB  - Cells in the cardiovascular system are constantly exposed to complex mechanical
      stimulation due to the pulsatile nature of blood flow and the haemodynamic forces
      that are key to the regulation of vascular development, remodeling and
      pathophysiology. Mechanical stretch can also modulate the differentiation of stem
      cells toward vascular cell lineages (i.e., vascular smooth muscle cells), and
      represent a critical factor in vascular tissue engineering. Here we report on the
      development of a microchip platform that can emulate several key aspects of the
      vascular mechanical environment, such as cyclic stimulation and circumferential
      strain. This chip consists of an array of microfluidic channels with widths
      ranging from 20 to 500 micrometers. These channels are covered by suspended
      deformable membranes, on which cells are cultured and stimulated by cyclic
      circumferential strain of up to 20% via hydrodynamic actuation of the fluid in
      the microfluidic channels, thereby mimicking the biomechanical conditions of
      small blood vessels. We show that human mesenchymal stem cells (MSCs) can be
      cultured and continuously stimulated by cyclic stretch over a period of 7 days
      with no evidence of device fatigue or performance degradation. We observed
      localization and alignment of MSCs when mechanical stretch is larger than 10%,
      indicating the importance of mechanical stimulation in modulating cellular
      behavior. We further demonstrated simultaneous detection of proteins in multiple
      signaling pathways, including SMAD1/SMAD2 and canonical Wnt/beta-catenin. This
      microchip represents a generic and versatile platform for high-throughput and
      rapid screening of cellular responses, including signal transduction cascades, in
      response to mechanical cues. The system emulates the physiological conditions of
      blood vessels and other tissues that are subject to cyclic strain, and may have a
      wide range of applications in the fields of stem cell mechanobiology, vascular
      tissue engineering, and other areas of regenerative medicine.

PMID- 23114827
TI  - Primary stability/mobility of 1-stage and 2-stage dental implants:  a comparative
      in vitro study.
AB  - PURPOSE: To evaluate the primary stability of 1-stage (nonsubmerged) and 2-stage
      (submerged) implants via newest wireless resonance frequency (RF) analyzer and
      newer wireless mobility measuring (MM) device. MATERIALS AND METHODS: Six 1-stage
      dental implants with internal hex connection and six 2-stage dental implants, 4.1
      mm in diameter and 11.5 mm in length, were inserted bilaterally into the first
      premolar, second premolar, and first molar regions of 6 standard mandibular
      transparent self-curing acrylic resin models. After that, the periimplant
      circular bone defects were created in millimeter increments ranging between 0 and
      5 mm to the same extent on all implants. RESULTS: Implant stability quotient
      values significantly decreased at 1-stage and 2-stage implants when periimplant
      defects increased. Similar implant stability quotient values were found for both
      implant types; however, significantly lower MM values were noted for 2-stage
      implants. Irrespective of implant systems, the results indicated a significant
      association between wireless RF analyzer and wireless MM device. CONCLUSION: Both
      wireless RF analyzer and wireless MM device were adequate in assessing implant
      stability. There was no difference between 2-stage and 1-stage implant systems,
      except lower MM values were noted for nonsubmerged implants.

PMID- 23114828
TI  - Implant stability measurements of two immediate loading protocols for the
      edentulous mandible: rigid and semi-rigid splinting of the implants.
AB  - AIM: Primary and secondary stabilities of immediately loaded mandibular implants
      restored with fixed prostheses (FP) using rigid or semi-rigid splinting systems
      were clinically and radiographically evaluated. METHODS: Fifteen edentulous
      patients were rehabilitated using hybrid FP; each had 5 implants placed between
      the mental foramens. Two groups were randomly divided: group 1-FP with the
      conventional rigid bar splinting the implants and group 2-semi-rigid cantilever
      extension system with titanium bars placed in the 2 distal abutment cylinders.
      Primary stability was evaluated using resonance frequency analysis after
      installation of the implant abutments. The measurements were made at 3 times: T0,
      at baseline; T1, 4 months after implant placement; and T2, 8 months after implant
      placement. Presence of mobility and inflammation in the implant surrounding
      regions were checked. Stability data were submitted to statistical analysis for
      comparison between groups (P < 0.05). RESULTS: Implant survival rate for the
      implants was of 100% in both groups. No significant differences in the mean
      implant stability quotient values were found for both groups from baseline and
      after the 8-month follow-up. CONCLUSION: The immediate loading of the implants
      was satisfactory, and both splinting conditions (rigid and semi-rigid) can be
      successfully used for the restoration of edentulous mandibles.

PMID- 23114829
TI  - Effect of static magnetic fields on the osseointegration of immediately placed
      implants:  a randomized controlled clinical trial.
AB  - PURPOSE: The aim of this study was to evaluate the effects of static magnetic
      fields (SMFs) on the implants immediately placed in fresh extraction sockets.
      MATERIALS AND METHODS: Twenty patients who were in need of 20 fixed implant
      supported single crowns in the anterior maxilla were included. After tooth
      extraction, screw-type implants were placed immediately into fresh extraction
      sockets and were randomly covered with either magnetic abutment (test group) or
      conventional healing abutment (control group). Radio frequency analysis (RFA) was
      conducted at implant placement and after 1, 2, and 3 months. Marginal bone level
      changes were recorded 1, 2, and 3 months postoperatively. RESULTS: The RFA
      measurements showed a significant higher stability for implants in test group
      than that of control group after 1 month (P = 0.04). At month 2, less crestal
      bone loss was found in the test group (P = 0.03). However, at month 3, there was
      no significant difference between the groups for both parameters (P > 0.05).
      CONCLUSION: SMFs caused more noticeable increase in implant stability and less
      bone loss during the initial weeks of healing.

PMID- 23114830
TI  - Ridge augmentation with mineralized block allografts:  clinical and histological
      evaluation of 8 cases treated with the 3-dimensional block technique.
AB  - PURPOSE: Bone augmentation is frequently used to create sufficient bone volume
      for ideal implant placement. Severely resorbed ridges require extensive bone
      augmentation in the form of block allografts. A 3-dimensional graft technique has
      been developed to augment atrophic areas. This technique involves modifying the
      graft on a sterile prototype of the recipient site before the surgery. This
      article investigates the clinical and histological outcomes of ridge augmentation
      using this technique. MATERIALS AND METHODS: Eight partially edentulous patients
      were recruited. Ridge augmentations were performed using block allografts,
      preadjusted, based on sterile prototypes of the recipient bed before the
      surgeries. After 8 months, 20 implants were inserted into the grafted sites.
      Eight bone cores were harvested for histological analysis. RESULT: Highly vital
      and mineralized bone with lamellar organization was observed at the grafted
      sites. CONCLUSION: Having the ability to modify the allogeneic block grafts to
      fit the recipient sites before the surgery minimized the surgical time and risk
      of postoperative complications such as infection. In addition, the clinician
      could concentrate fully on achieving tension-free primary wound closure.

PMID- 23114831
TI  - Topographic analysis of maxillary premolars and molars and maxillary sinus using
      cone beam computed tomography.
AB  - PURPOSE: This study evaluated the anatomical characteristics of the maxillary
      premolars and molars and the maxillary sinus using cone beam computed tomography
      (CBCT) for dental implant treatment. MATERIALS AND METHODS: Ten linear items and
      1 angular item on 30 sites in 30 patients were measured on 3-dimensional computed
      tomography images using CBCT. The vertical relationship between the maxillary
      sinus and the maxillary molars was classified into 5 categories. RESULTS: The
      horizontal thickness of the buccal alveolar bone was thinnest on the maxillary
      first premolars, and the horizontal thickness of the palatal alveolar bone was
      thickest on the maxillary second molars. Type II was most common on the maxillary
      first molars. The internal angle at the maxillary premolars was significantly
      greater than that at the maxillary molars. The internal angle and vertical
      distance between the apex of the roots and the maxillary sinus floor showed a
      positive correlation on the maxillary first premolars (P = 0.003). CONCLUSION:
      For the selection of an appropriate approach on dental implant treatment, the
      evaluation of maxillary premolars and molars using of CBCT can be recommended.

PMID- 23114832
TI  - PEGylated dendrimer polystyrene support: synthesis, characterisation and
      evaluation of biologically active peptides.
AB  - Poly(N,N-bisethylamine) dendrimers with high content of poly(ethylene glycol)
      were synthesized on 3-(Acryloyloxy)-2-hydroxypropylmethacrylate-crosslinked
      polystyrene (PS-AHMA) resin and tested in various conditions of solid phase
      peptide synthesis. The dendritic templates were generated to the second
      generation on cross-linker active site of 3-(Acryloyloxy)-2
      hydroxypropylmethacrylate (AHMA). First generation dendrimer was designed by
      series of four-stage reactions, such as Schiff base incorporation, acidolytic
      cleavage, diazotization and thionyl chloride treatment and same synthetic routes
      were followed for second generation also. Poly(ethylene glycol) (PEG1000) has
      been grafted to second-generation dendrimer and used to check various physico
      chemical parameters in Fmoc/Boc peptide synthetic conditions. The utility of
      PEGylated dendrimer support was demonstrated by synthesizing biologically potent
      linear as well as disulfide-bonded peptide by Fmoc method.

PMID- 23114834
TI  - Sizing up microbes.
AB  - The size range of life forms is dictated by basic principles of physics. Large
      microorganisms, with sizes approaching a millimeter, have compensating features
      that address the immutable laws of physics. For pathogens, size may impact a
      range of functions, such as adherence and immune evasion. We review several
      recent studies on factors impacting, and impacted by, the size of microorganisms.

PMID- 23114833
TI  - Contribution of nonesterified fatty acids to mitogen-activated protein kinase
      activation in human skeletal muscle during endurance exercise.
AB  - Mitogen-activated protein kinase (MAPK) pathways are activated in skeletal muscle
      during endurance exercise, but the upstream molecular events are incompletely
      resolved. As an increase in plasma nonesterified fatty acids (NEFA) is a common
      feature of long-lasting exercise, the authors tested the hypothesis that NEFA
      contribute to the activation of MAPK during endurance exercise. Acipimox was used
      before and during endurance exercise to prevent the elevation of plasma NEFA
      levels in healthy subjects and patients with diabetes. In 2 separate studies,
      healthy subjects cycled for 2 hr and patients with diabetes for 1 hr at 50% Wmax.
      In control conditions, plasma NEFA concentrations increased from 0.35 to 0.90 mM
      during exercise in healthy subjects and from 0.55 to 0.70 mM in patients with
      diabetes (p < .05). Phosphorylation states of extracellularly regulated kinase 1
      and 2 (ERK1/2), p38, and c-Jun NH2-terminal kinases (JNK) were significantly
      increased after exercise in the vastus lateralis in both groups. Acipimox blocked
      the increase in plasma NEFA concentrations and almost completely repressed any
      rise in ERK1/2 and p38 but not in JNK. In conclusion, the data support a role for
      plasma NEFA in the activation of p38 and ERK1/2 in skeletal-muscle tissue of
      healthy and diabetic subjects during endurance exercise. Further investigation
      will be required to determine the molecular link between NEFA and MAPK activation
      during exercise in human skeletal muscle.

PMID- 23114835
TI  - Religiosity and exposure to users in explaining illicit drug use among emerging
      adults.
AB  - Religiosity is a protective factor against illicit drug use, but further
      investigation is needed to delineate which components of religiosity are
      protective against use. A racially diverse sample (N = 962) was surveyed about
      religiosity, exposure to users, and recent use of marijuana, powder cocaine,
      ecstasy, and nonmedical use of opioids and amphetamine. Results suggest that
      identifying as Agnostic increased odds of use for each of the five drugs;
      however, this effect disappeared when controlling for religious importance and
      attendance. High levels of religious attendance were protective against recent
      use of marijuana and cocaine, but protective effects diminished when controlling
      for exposure to users, which was a robust predictor of use of every drug.
      Religion is a protective mechanism against drug use, but this effect may diminish
      in light of exposure to users. Alternative preventative methods need to be
      directed toward individuals who are not religious or are highly exposed to users.

PMID- 23114837
TI  - Abandoned coal mining sites: using ecotoxicological tests to support an
      industrial organic sludge amendment.
AB  - The different stages involved in coal mining-related activities result in a
      degraded landscape and sites associated with large amounts of dumped waste
      material. Remediation of these contaminated soils can be carried out by
      application of industrial organic sludge if the concerns regarding the potential
      negative environmental impacts of this experimental practice are properly
      addressed. In this context, the objective of this study was to use
      ecotoxicological tests to determine the quantity of organic industrial sludge
      that is required as a soil amendment to restore soil production while avoiding
      environmental impact. Chemical analysis of the solids (industrial sludge and
      soil) and their leachates was carried out as well as a battery of ecotoxicity
      tests on enzymes (hydrolytic activity), bacteria, algae, daphnids, earthworms,
      and higher plants, according to standardized methodologies. Solid and leachate
      samples of coal-contaminated soil were more toxic than those of industrial sludge
      towards enzyme activity, bacteria, algae, daphnids, and earthworms. In the case
      of the higher plants (lettuce, corn, wild cabbage, and Surinam cherry) the
      industrial sludge was more toxic than the coal-contaminated soil, and a
      soil/sludge mixture (66:34% dry weight basis) had a stimulatory effect on the
      Surinam cherry biomass. The ecotoxicological assessment of the coal-contaminated
      soil remediation using sludge as an amendment is very important to determine
      application rates that could promote a stimulatory effect on agronomic species
      without negatively affecting the environment.

PMID- 23114839
TI  - Solar photocatalytic degradation of mono azo methyl orange and diazo reactive
      green 19 in single and binary dye solutions: adsorbability vs photodegradation
      rate.
AB  - The objective of this study was to examine the effects of adsorbability and
      number of sulfonate group on solar photocatalytic degradation of mono azo methyl
      orange (MO) and diazo Reactive Green 19 (RG19) in single and binary dye
      solutions. The adsorption capacity of MO and RG19 onto the TiO2 was 16.9 and 26.8
      mg/g, respectively, in single dye solution, and reduced to 5.0 and 23.1 mg/g,
      respectively, in the binary dye solution. The data obtained for photocatalytic
      degradation of MO and RG19 in single and binary dye solution were well fitted
      with the Langmuir-Hinshelwood kinetic model. The pseudo-first-order rate
      constants of diazo RG19 were significant higher than the mono azo MO either in
      single or binary dye solutions. The higher number of sulfonate group in RG19
      contributed to better adsorption capacity onto the surface of TiO2 than MO
      indicating greater photocatalytic degradation rate.

PMID- 23114838
TI  - Simultaneous adsorption and degradation of Zn(2+) and Cu (2+) from wastewaters
      using nanoscale zero-valent iron impregnated with clays.
AB  - Clays such as kaolin, bentonite and zeolite were evaluated as support material
      for nanoscale zero-valent iron (nZVI) to simultaneously remove Cu(2+) and Zn(2+)
      from aqueous solution. Of the three supported nZVIs, bentonite-supported nZVI (B
      nZVI) was most effective in the simultaneous removal of Cu(2+) and Zn(2+) from a
      aqueous solution containing a 100 mg/l of Cu(2+) and Zn(2+), where 92.9 % Cu(2+)
      and 58.3 % Zn(2+) were removed. Scanning electronic microscope (SEM) revealed
      that the aggregation of nZVI decreased as the proportion of bentonite increased
      due to the good dispersion of nZVI, while energy dispersive spectroscopy (EDS)
      demonstrated the deposition of copper and zinc on B-nZVI after B-nZVI reacted
      with Cu(2+) and Zn(2+). A kinetics study indicated that removing Cu(2+) and
      Zn(2+) with B-nZVI accorded with the pseudo first-order model. These suggest that
      simultaneous adsorption of Cu(2+)and Zn(2+) on bentonite and the degradation of
      Cu(2+)and Zn(2+) by nZVI on the bentonite. However, Cu(2+) removal by B-nZVI was
      reduced rather than adsorption, while Zn(2+) removal was main adsorption.
      Finally, Cu(2+), Zn(2+), Ni(2+), Pb(2+) and total Cr from various wastewaters
      were removed by B-nZVI, and reusability of B-nZVI with different treatment was
      tested, which demonstrates that B-nZVI is a potential material for the removal of
      heavy metals from wastewaters.

PMID- 23114840
TI  - Plasma cholinesterase activity in the house finch, Carpodacus mexicanus, and the
      house sparrow, Passer domesticus, collected from pesticide-exposed agricultural
      land.
AB  - Agricultural lands are exposed to pesticides continuously, which impact on
      habitat of wild species, such birds. The purpose of this study was to determine
      the plasma cholinesterase activity in two passeriform wild birds, the house finch
      (Carpodacus mexicanus) and the house sparrow (Passer domesticus), from
      agricultural land with exposure to pesticides. No significant difference was
      found in the house finch between specimens captured in non-agricultural and
      agricultural lands. However, house sparrows had significant differences in plasma
      cholinesterase activity, which indicates that this species is more sensitive to
      enzymatic activity inhibition by pesticides, and they could be indicators of
      pesticide pollution in agricultural areas.

PMID- 23114841
TI  - Conceptions on genetics in a group of college students.
AB  - The purpose of this study was to investigate awareness, beliefs, and opinions on
      genetics in a group of Brazilian college students from several courses. The study
      used the focus group technique with the participation of 19 students, divided
      into four groups. Also, it used the isotopic reading technique to analyze the
      material. The results were divided in four themes: the basic knowledge of
      genetics, the "new genetics," including molecular biology and testing, genetic
      manipulation, and genetics and the media. The participants showed reasonable
      knowledge on the subject, obtained from various sources, including the printed
      press, the internet, documentaries, and fictional TV shows. Ethical issues were
      discussed comprehensively and the groups showed awareness on the hazards brought
      by genetic reductionism and the need to have some type of regulation regarding
      genetic manipulation and testing. It is necessary to broaden the debate about the
      progress in genetics because some of them will affect a significant number of
      people. This debate should include the lay public, which has been actively
      participating in decisions involving research and the use of new technologies.

PMID- 23114844
TI  - Tackling hepatitis B virus-associated hepatocellular carcinoma--the future is
      now.
AB  - Hepatocellular carcinoma (HCC) is one of the most lethal and prevalent cancers in
      many developing countries including India. Among the various etiological factors
      being implicated in the cause of HCC, the most important cause, however, is
      hepatitis B virus (HBV) infection. Among all HBV genes, HBx is the most critical
      carcinogenic component, the molecular mechanisms of which have not been
      completely elucidated. Despite its clinical significance, there exists a very
      elemental understanding of the molecular, cellular, and environmental mechanisms
      that drive disease pathogenesis in HCC infected with HBV. Furthermore, there are
      only limited therapeutic options, the clinical benefits of which are
      insignificant. Therefore, the quest for novel and effective therapeutic regimen
      against HBV-related HCC is of paramount importance. This review attempts to
      epitomize the current state of knowledge of this most common and dreaded liver
      neoplasm, highlighting the putative treatment avenues and therapeutic research
      strategies that need to be implemented with immediate effect for tackling HBV
      related HCC that has plagued the medical and scientific fraternity for decades.
      Additionally, this review proposes a novel "five-point" management algorithm for
      HBV-related HCC apart from portraying the unmet needs, principal challenges, and
      scientific perspectives that are relevant to controlling this accelerating global
      health crisis.

PMID- 23114843
TI  - Modeling prostate cancer in mice: something old, something new, something
      premalignant, something metastatic.
AB  - More than 15 years ago, the first generation of genetically engineered mouse
      (GEM) models of prostate cancer was introduced. These transgenic models utilized
      prostate-specific promoters to express SV40 oncogenes specifically in prostate
      epithelium. Since the description of these initial models, there have been a
      plethora of GEM models of prostate cancer representing various perturbations of
      oncogenes or tumor suppressors, either alone or in combination. This review
      describes these GEM models, focusing on their relevance for human prostate cancer
      and highlighting their strengths and limitations, as well as opportunities for
      the future.

PMID- 23114842
TI  - Challenges and advances in mouse modeling for human pancreatic tumorigenesis and
      metastasis.
AB  - Pancreatic cancer is critical for developed countries, where its rate of
      diagnosis has been increasing steadily annually. In the past decade, the advances
      of pancreatic cancer research have not contributed to the decline in mortality
      rates from pancreatic cancer-the overall 5-year survival rate remains about 5%
      low. This number only underscores an obvious urgency for us to better understand
      the biological features of pancreatic carcinogenesis, to develop early detection
      methods, and to improve novel therapeutic treatments. To achieve these goals,
      animal modeling that faithfully recapitulates the whole process of human
      pancreatic cancer is central to making the advancements. In this review, we
      summarize the currently available animal models for pancreatic cancer and the
      advances in pancreatic cancer animal modeling. We compare and contrast the
      advantages and disadvantages of three major categories of these models: (1)
      carcinogen-induced; (2) xenograft and allograft; and (3) genetically engineered
      mouse models. We focus more on the genetically engineered mouse models, a
      category which has been rapidly expanded recently for their capacities to mimic
      human pancreatic cancer and metastasis, and highlight the combinations of these
      models with various newly developed strategies and cell-lineage labeling systems.

PMID- 23114845
TI  - Heading off with the herd: how cancer cells might maneuver supernumerary
      centrosomes for directional migration.
AB  - The complicity of centrosomes in carcinogenesis is unmistakable. Mounting
      evidence clearly implicates a robust correlation between centrosome amplification
      (CA) and malignant transformation in diverse tissue types. Furthermore, CA has
      been suggested as a marker of cancer aggressiveness, in particular the invasive
      phenotype, in breast and prostate cancers. One means by which CA promotes
      malignancy is through induction of transient spindle multipolarity during
      mitosis, which predisposes the cell to karyotypic changes arising from low-grade
      chromosome mis-segregation. It is well recognized that during cell migration in
      interphase, centrosome-mediated nucleation of a radial microtubule array is
      crucial for establishing a polarized Golgi apparatus, without which
      directionality is precluded. The question of how cancer cells maneuver their
      supernumerary centrosomes to achieve directionality during cell migration is
      virtually uncharted territory. Given that CA is a hallmark of cancers and has
      been correlated with cancer aggressiveness, malignant cells are presumably
      competent in managing their centrosome surfeit during directional migration,
      although the cellular logistics of this process remain unexplored. Another key
      angle worth pondering is whether an overabundance of centrosomes confers some
      advantage on cancer cells in terms of their migratory and invasive capabilities.
      Recent studies have uncovered a remarkable strategy that cancer cells employ to
      deal with the problem of excess centrosomes and ensure bipolar mitoses, viz.,
      centrosome clustering. This review aims to change the narrative by exploring how
      an increased centrosome complement may, via aneuploidy-independent modulation of
      the microtubule cytoskeleton, enhance directional migration and invasion of
      malignant cells. We postulate that CA imbues cancer cells with cytoskeletal
      advantages that enhance cell polarization, Golgi-dependent vesicular trafficking,
      stromal invasion, and other aspects of metastatic progression. We also propose
      that centrosome declustering may represent a novel, cancer cell-specific
      antimetastatic strategy, as cancer cells may rely on centrosome clustering during
      migration as they do in mitosis. Elucidation of these details offers an exciting
      avenue for future research, as does investigating how CA may promote metastasis
      through enhanced directional migration.

PMID- 23114848
TI  - Reply to correspondence letter by M. Korppi.

PMID- 23114847
TI  - Genodermatoses caused by genetic mosaicism.
AB  - Genetic mosaicism is defined as the existence of at least two genetically
      distinct cell populations within one individual. Mosaic presentation of genetic
      disorders is common and is often particularly obvious in the skin, because there
      it will generate recognizable patterns. Recognizing those can frequently assist
      in establishing a diagnosis. In this review, we discuss the mechanisms that give
      rise to genetic mosaicism. We describe its most frequent cutaneous manifestations
      that are relevant to paediatric practice. While most mosaic genetic diseases are
      rare, it is important to recognize them so that patients and parents may receive
      appropriate genetic counselling. Moreover, recent developments are now resulting
      in novel, targeted treatments for such disorders that promise to considerably
      improve patients' lives.

PMID- 23114846
TI  - Stromal cells in tumor microenvironment and breast cancer.
AB  - Cancer is a systemic disease encompassing multiple components of both tumor cells
      themselves and host stromal cells. It is now clear that stromal cells in the
      tumor microenvironment play an important role in cancer development. Molecular
      events through which reactive stromal cells affect cancer cells can be defined so
      that biomarkers and therapeutic targets can be identified. Cancer-associated
      fibroblasts (CAFs) make up the bulk of cancer stroma and affect the tumor
      microenvironment such that they promote cancer initiation, angiogenesis,
      invasion, and metastasis. In breast cancer, CAFs not only promote tumor
      progression but also induce therapeutic resistance. Accordingly, targeting CAFs
      provides a novel way to control tumors with therapeutic resistance. This review
      summarizes the current understandings of tumor stroma in breast cancer with a
      particular emphasis on the role of CAFs and the therapeutic implications of CAFs.
      In addition, the effects of other stromal components such as endothelial cells,
      macrophages, and adipocytes in breast cancer are also discussed. Finally, we
      describe the biologic markers to categorize patients into a specific and
      confirmed subtype for personalized treatment.

PMID- 23114849
TI  - Lactobacillus GG (LGG) and smectite versus LGG alone for acute gastroenteritis: a
      double-blind, randomized controlled trial.
AB  - Diarrhea treatment with either Lactobacillus GG (LGG) or smectite as an adjuvant
      to standard rehydration therapy has proven efficacy. In countries where both LGG
      and smectite are available, concomitant use is frequently practiced. We
      investigated whether LGG plus smectite is superior to LGG alone in the management
      of children with acute gastroenteritis (AGE). A double-blind, placebo-controlled,
      randomized trial was performed. Children aged 4 to 60 months with AGE received
      LGG 6 * 10(9) colony forming units/day plus randomly either smectite (3 g) or
      placebo as an adjuvant to the standard rehydration therapy. Of the 88 children
      randomized, 81 (92 %) were available for intention-to-treat analysis. The
      duration of diarrhea in the LGG/smectite group (n = 44) compared with the
      LGG/placebo group (n = 37) was similar (P = 0.43). There were no significant
      differences between the study groups for the secondary outcomes, with three
      exceptions. On day 4, in the LGG/placebo group compared to the LGG/smectite
      group, there was significantly reduced stool frequency (P = 0.03). While there
      was a significant (P = 0.05) difference in stool consistency on the Bristol Stool
      Form Scale on day 4, it was not of clinical relevance. Finally, in the
      LGG/smectite group compared to the LGG/placebo group, there was a significantly
      shorter duration of intravenous therapy after randomization (P = 0.02). No
      adverse events were observed in the study groups. CONCLUSION: LGG plus smectite
      and LGG alone are equally effective for treating young children with AGE.
      Combined use of the two interventions is not justified.

PMID- 23114854
TI  - Phylogeography of mitochondrial haplogroup D1: an early spread of subhaplogroup
      D1j from Central Argentina.
AB  - We analyzed the patterns of variation of haplogroup D1 in central Argentina,
      including new data and published information from other populations of South
      America. Almost 28% (107/388) of the individuals sampled in the region belong to
      haplogroup D1, whereas more than 52% of them correspond to the recently described
      subhaplogroup D1j (Bodner et al.: Genome Res 22 (2012) 811-820), defined by the
      presence of additional transitions at np T152C-C16242T-T16311C to the nodal D1
      motif. This lineage was found at high frequencies across a wide territory with
      marked geographical-ecological differences. Additionally, 12 individuals present
      the mutation C16187T that defines the recently named subhaplogroup D1g (Bodner et
      al.: Genome Res 22 (2012) 811-820), previously described in populations of
      Patagonia and Tierra del Fuego. Based on our results and additional data already
      published, we postulate that the most likely origin of subhaplogroup D1j is the
      region of Sierras Pampeanas, which occupies the center and part of the
      northwestern portion of Argentina. The extensive yet restricted geographical
      distribution, the relatively large internal diversity, and the absence or low
      incidence of D1j in other regions of South America suggest the existence of an
      ancient metapopulation covering the Sierras Pampeanas, being this lineage its
      genetic signature. Further support for a scenario of local origin for D1j in the
      Sierras Pampeanas stems from the fact that early derivatives from a putative
      ancestral lineage carrying the transitions T16311C-T152C have only been found in
      this region, supporting the hypothesis that it might represent an ancestral motif
      previous to the appearance of D1j-specific change C16242T.

PMID- 23114856
TI  - In vivo pre- and postoperative three-dimensional knee kinematics in
      unicompartmental knee arthroplasty.
AB  - BACKGROUND: Pre- and postoperative knee kinematics in unicompartmental knee
      arthroplasty (UKA) can be theoretically related to clinical outcome and longevity
      after UKA with regard to ligament function and the degree of arthritic changes.
      However, the preoperative knee kinematics of patients indicated for UKA remain to
      be elucidated, and it is also unclear whether the preoperative kinematics can be
      maintained by the UKA procedure. The objective of this study was to examine the
      in vivo pre- and postoperative three-dimensional knee kinematics in UKA while
      referencing the normal knee kinematics reported in our previous study. METHODS:
      We analyzed the knee kinematics in 17 knees (14 patients) undergoing UKA via a
      three-dimensional to two-dimensional registration technique employing femoral
      condylar translation and femoral axial rotation. The pre- and postoperative knee
      kinematics during squat motion were evaluated in the same subjects, employing
      consistent evaluation parameters. RESULTS: On average, both pre- and
      postoperative knee kinematics in the range 10-100 degrees  of knee flexion
      demonstrated near-consistent femoral external rotation and anterior translation
      of the medial condyle and posterior translation of the lateral condyle. However,
      the mean femoral external rotation angle and the posterior translation of the
      lateral condyle postoperatively were significantly smaller than the values
      observed preoperatively. DISCUSSION: Although the patterns of preoperative knee
      motion were similar to those seen in normal knees, the magnitude of this motion
      varied widely between patients, so it was not necessarily representative of
      normal knees. These variations may be due to the varying degrees of arthritic
      changes caused by osteoarthritis. Although the patterns of knee kinematics were
      largely maintained by the UKA procedure, the causes of the significant reductions
      in the magnitude of motion upon performing the UKA procedure should be
      investigated in subsequent studies with a larger number of patients.

PMID- 23114857
TI  - Evaluation of locomotive disability using loco-check: a cross-sectional study in
      the Japanese general population.
AB  - BACKGROUND: The purposes of this study were to reveal the prevalence of
      locomotive syndrome (LS) evaluated by loco-check in the Japanese general
      population and to analyze the relationship between radiographic knee
      osteoarthritis (OA) and lumbar spondylosis, metabolic syndrome and LS.
      Furthermore, we evaluated LS according to functional examinations. METHODS: Seven
      hundred twenty-two volunteers aged 56.6 +/- 13.6 years participated in the Iwaki
      Health Promotion Project in 2010 and were classified into two groups: LS (one or
      more disabilities) or non-LS (no disability) according to the criteria of LS
      proposed by the Japanese Orthopaedic Association. Radiographic knee OA and lumbar
      spondylosis were defined according to the Kellgren-Lawrence grade. Metabolic
      syndrome was defined as the presence of two or more risk factors in addition to
      visceral obesity. The prevalence of LS associated with knee OA, lumbar
      spondylosis and metabolic syndrome was compared statistically. Also, data of six
      functional examinations were compared between the non-LS and LS groups. RESULTS:
      The prevalence of LS was 21.2 % in males and 35.6 % in females and increased with
      aging regardless of gender. The prevalence of LS with knee OA was 48.7 %, with
      lumbar spondylosis was 33.8 %, and with metabolic syndrome was 43.4 %. The non-LS
      group had significantly better performance in the functional reach and sit and
      reach tests than the LS group in males and females by age-adjusted comparison.
      CONCLUSION: The prevalence of LS in the general population was higher in females
      than in males. A strong risk factor for LS was radiographic knee OA. Also, those
      with LS had loss of skeletal muscle mass, balancing and flexibility. This study
      showed that evaluation by loco-check was an acceptable tool to detect the early
      stage of locomotive disability for LS, and interventional prevention for
      strength, balancing and flexibility would be helpful for those with LS.

PMID- 23114858
TI  - Logistic regression analysis of factors associated with avascular necrosis of the
      femoral head following femoral neck fractures in middle-aged and elderly
      patients.
AB  - BACKGROUND: Risk factors for femoral neck fracture-induced avascular necrosis of
      the femoral head have not been elucidated clearly in middle-aged and elderly
      patients. Moreover, the high incidence of screw removal in China and its effect
      on the fate of the involved femoral head require statistical methods to reflect
      their intrinsic relationship. METHODS: Ninety-nine patients older than 45 years
      with femoral neck fracture were treated by internal fixation between May 1999 and
      April 2004. Descriptive analysis, interaction analysis between associated
      factors, single factor logistic regression, multivariate logistic regression, and
      detailed interaction analysis were employed to explore potential relationships
      among associated factors. RESULTS: Avascular necrosis of the femoral head was
      found in 15 cases (15.2 %). Age * the status of implants (removal vs.
      maintenance) and gender * the timing of reduction were interactive according to
      two-factor interactive analysis. Age, the displacement of fractures, the quality
      of reduction, and the status of implants were found to be significant factors in
      single factor logistic regression analysis. Age, age * the status of implants,
      and the quality of reduction were found to be significant factors in multivariate
      logistic regression analysis. In fine interaction analysis after multivariate
      logistic regression analysis, implant removal was the most important risk factor
      for avascular necrosis in 56-to-85-year-old patients, with a risk ratio of 26.00
      (95 % CI = 3.076-219.747). CONCLUSION: The middle-aged and elderly have less
      incidence of avascular necrosis of the femoral head following femoral neck
      fractures treated by cannulated screws. The removal of cannulated screws can
      induce a significantly high incidence of avascular necrosis of the femoral head
      in elderly patients, while a high-quality reduction is helpful to reduce
      avascular necrosis.

PMID- 23114859
TI  - A new treatment strategy for Kienbock's disease: combination of bone marrow
      transfusion, low-intensity pulsed ultrasound therapy, and external fixation.
AB  - BACKGROUND: The purpose of this study was to investigate the midterm clinical and
      radiographic outcomes of this new treatment for Kienbock's disease. METHODS: We
      applied a new method involving drilling, bone marrow transfusion, external
      fixation, and low-intensity pulsed ultrasound for patients with Kienbock's
      disease. Between 2000 and 2006, the treatment was performed in 18 patients (10
      men and 8 women; 9 right wrists and 9 left wrists). The preoperative Lichtman
      stages were stage II in 4 cases, stage IIIa in 11 cases, and stage IIIb in 3
      cases. The mean age at surgery was 44.9 years (range 16-68 years), and the mean
      follow-up period was 63 months (range 28-125 months). The overall results were
      evaluated using the Mayo wrist score and Nakamura scoring system for Kienbock's
      disease. Magnetic resonance imaging (MRI) was performed for all patients.
      RESULTS: Wrist pain improved to no pain in 13 patients, mild pain in 4 patients,
      and moderate pain in 1 patient. The average wrist flexion-extension arc was 100
      degrees  and averaged 120 % of the preoperative value. The average grip strength
      increased from 50 to 85 % relative to the unaffected side. On roentgenograms, the
      carpal height ratio (change from 0.53 to 0.51) and the Stahl index (change from
      0.38 to 0.32) decreased slightly. On MRI, fatty marrow was recovered in 11
      patients (61 %) on proton density-weighted images. CONCLUSIONS: This method can
      be used as a less-invasive surgical treatment alternative for Kienbock's disease.
      At an average follow-up period of 6 years, this new treatment has been shown to
      be a reliable and durable procedure for patients with Lichtman stage II or stage
      III Kienbock's disease. Caution should be exercised for patients with a
      fragmented lunate because of the risk of collapse and nonunion of the lunate.

PMID- 23114860
TI  - Microspectroscopy reveals mechanisms of lymphocyte activation.
AB  - The immunological synapse (IS) regulates immune responses by integrating
      extracellular stimuli into intracellular signalling networks, which causes
      leukocyte differentiation and effector functions. The dynamic spatial
      organisation of molecules at the IS was initially characterised by wide-field
      fluorescence microscopy of cell conjugates and cells interacting with planar
      lipid bilayers. These methods showed stable supramolecular clusters of several
      microns in size, which were proposed to be responsible for sustained signalling
      and cell-cell adhesion. The recent emergence of microspectroscopy techniques with
      higher spatial and temporal resolution nonetheless reveals the complex dynamics
      of molecular reactions that mediate IS assembly and function. This review
      describes microspectroscopy-based in vitro experimental approaches for imaging
      the molecular dynamics at the IS, as well as their contributions and open
      questions in the field. It also describes experimental methods to obtain
      quantitative parameters of dynamic biochemical reactions in living cells, and
      discusses about the important role of quantitative imaging and theoretical
      science in our understanding of molecular mechanisms underlying lymphocyte
      activation.

PMID- 23114861
TI  - The burden of maternal health care expenditure in India: multilevel analysis of
      national data.
AB  - To quantify the economic burden of maternal health care services on Indian
      households and examine the levels of expenditure incurred in public and private
      health care institutions at the national, state and community levels. Cross
      sectional population data from the 2004 National Sample Survey Organisation were
      used, which considered 9,643 households for the analysis where at least one woman
      received maternal health care services during the year preceding the survey.
      Multilevel linear regression techniques were used to estimate the effect of
      household, cluster and state characteristics on the proportion of maternal health
      care expenditures over total household expenditures. Over 80 % of households
      reported paying for maternal health care services, with those using private care
      facilities paying almost 4 times more than those using public facilities.
      Multilevel analyses show evidence of high burden of maternal health care
      expenditures, which varied significantly across states according to the level of
      health care utilisation, and with considerable heterogeneity at the household and
      community levels. Maternal health care services in India are offered free at the
      point of delivery, yet many families face significant out-of-pocket expenditures.
      The recent governmental policy interventions to encourage institutional births by
      providing nominal financial assistance is a welcome step but this might not help
      to compensate mothers for other indirect expenditures, especially those living in
      rural areas and poorer communities who are increasingly seeking care in private
      facilities. 

PMID- 23114862
TI  - White matter abnormalities in gene-positive myoclonus-dystonia.
AB  - Myoclonus-dystonia is an autosomal dominantly inherited movement disorder
      clinically characterized by myoclonic jerks and dystonic movements of the upper
      body. Functional imaging and structural gray matter imaging studies in M-D
      suggest defective sensorimotor integration and an association between putaminal
      volume and severity of dystonia, possibly because of neuronal plasticity. As we
      expect changes in the connections between the cortical and subcortical regions,
      we performed a combination of white matter voxel-based morphometry (wVBM) and
      diffusion tensor imaging (DTI) to detect macro- and microstructural white matter
      changes, respectively, in DYT-11 mutations carriers (M-D). Sixteen clinically
      affected DYT-11 mutation carriers and 18 control subjects were scanned with 3
      Tesla MRI to compare white matter volume, fractional anisotropy, and mean
      diffusivity between groups. In DYT11 mutation carriers, increased white matter
      volume and FA and decreased mean diffusivity were found in the subthalamic area
      of the brain stem, including the red nucleus. Furthermore, decreased mean
      diffusivity was found in the subgyral cortical sensorimotor areas. The white
      matter changes found in the subthalamic area of the brain stem, connecting the
      cerebellum with the thalamus, are compatible with the hypothesis that abnormal
      function in M-D involves a network that includes the cerebellum, brain stem, and
      basal ganglia. Whether these changes are causative or an effect of M-D requires
      further study.

PMID- 23114863
TI  - Water PMF for predicting the properties of water molecules in protein binding
      site.
AB  - Water is an important component in living systems and deserves better
      understanding in chemistry and biology. However, due to the difficulty of
      investigating the water functions in protein structures, it is usually ignored in
      computational modeling, especially in the field of computer-aided drug design.
      Here, using the potential of mean forces (PMFs) approach, we constructed a water
      PMF (wPMF) based on 3946 non-redundant high resolution crystal structures. The
      extracted wPMF potential was first used to investigate the structure pattern of
      water and analyze the residue hydrophilicity. Then, the relationship between wPMF
      score and the B factor value of crystal waters was studied. It was found that
      wPMF agrees well with some previously reported experimental observations. In
      addition, the wPMF score was also tested in parallel with 3D-RISM to measure the
      ability of retrieving experimentally observed waters, and showed comparable
      performance but with much less computational cost. In the end, we proposed a grid
      based clustering scheme together with a distance weighted wPMF score to further
      extend wPMF to predict the potential hydration sites of protein structure. From
      the test, this approach can predict the hydration site at the accuracy about 80%
      when the calculated score lower than -4.0. It also allows the assessment of
      whether or not a given water molecule should be targeted for displacement in
      ligand design. Overall, the wPMF presented here provides an optional solution to
      many water related computational modeling problems, some of which can be highly
      valuable as part of a rational drug design strategy.

PMID- 23114865
TI  - Reconstruction of posterior glenoid deficiency using distal tibial osteoarticular
      allograft.
AB  - Posterior shoulder instability with glenoid deficiency is a rare entity and its
      surgical treatment is challenging. Reconstructive techniques have focused on
      extra-articular structural bone transfer that obstructs humeral translation and
      thereby prevents glenohumeral dislocation. However, long-term results are not as
      promising. In this report, the authors describe a technique for anatomic
      posterior glenoid reconstruction using an osteoarticular distal tibia allograft
      in two patients including their outcomes after 2 years. Level of evidence IV.

PMID- 23114866
TI  - 'Web impingement' of the ankle: a case report. Reply to the comments made by
      Michel P. J. van den Bekerom and Eric E. J. Raven.

PMID- 23114864
TI  - The dynamic interdependence of amebiasis, innate immunity, and undernutrition.
AB  - Entamoeba histolytica, the protozoan parasite that causes amebic dysentery,
      greatly contributes to disease burden in the developing world. Efforts to
      exhaustively characterize the pathogenesis of amebiasis have increased our
      understanding of the dynamic host-parasite interaction and the process by which
      E. histolytica trophozoites transition from gut commensals to invaders of the
      intestinal epithelium. Mouse models of disease continue to be instrumental in
      this area. At the same time, large-scale studies in human populations have
      identified genetic and environmental factors that influence susceptibility to
      amebiasis. Nutritional status has long been known to globally influence immune
      function. So it is not surprising that undernutrition has emerged as a critical
      risk factor. A better understanding of how nutritional status affects immunity to
      E. histolytica will have dramatic implications in the development of novel
      treatments. Future work should continue to characterize the fascinating host
      parasite arms race that occurs at each stage of infection.

PMID- 23114867
TI  - Three-dimensional motion analysis of the human knee joint: comparison between
      intra- and post-operative measurements.
AB  - PURPOSE: To compare intra-operative knee joint kinematic measurements immediately
      after total knee replacement with those of the same patients post-operatively at
      6-month follow-up. METHODS: Fifteen patients who underwent total knee
      arthroplasty were analysed retrospectively. Eight were implanted with one
      prosthesis design and seven with another. The intra-operative measurements were
      performed by using a standard knee navigation system. This provided accurate
      three-dimensional positions and orientations for the femur and tibia by
      corresponding trackers pinned into the bones. At 6-month follow-up, the patients
      were analysed by standard three-dimensional video-fluoroscopy of the replaced
      knee during stair climbing, chair rising and step-up. Relevant three-dimensional
      positions and orientations were obtained by an iterative shape-matching procedure
      between the silhouette contours and the CAD-model projections. A number of
      traditional kinematic parameters were calculated from both measurements to
      represent the joint motion. RESULTS: Good post-operative replication of the intra
      operative measurements was observed for most of the variables analysed. The
      statistical analysis also supported the good consistency between the intra- and
      post-operative measurements. CONCLUSIONS: Intra-operative kinematic measurements,
      accessible by a surgical navigation system, are predictive of the following
      motion performance of the replaced knees as experienced in typical activities of
      daily living. LEVEL OF EVIDENCE: Prognostic studies--investigating natural
      history and evaluating the effect of a patient characteristic, Level II.

PMID- 23114868
TI  - The influence of the tibial plateau slopes on injury of the anterior cruciate
      ligament: a meta-analysis.
AB  - PURPOSE: The purpose of this meta-analysis was (1) to examine the effect of the
      tibial plateau slopes (medial and lateral) on anterior cruciate ligament (ACL)
      injury and (2) to investigate gender differences between ACL-injured subjects and
      gender-matched controls. METHODS: The PubMed database was searched through to 1
      November 2011 to identify studies that met pre-stated inclusion criteria.
      Reference lists of retrieved articles were also reviewed. Two authors
      independently extracted information on the designs of the studies, the
      characteristics of the study participants, exposure and outcome assessments, and
      control for potential confounding factors. A meta-analysis was conducted, and
      either a fixed- or a random-effects model was used to calculate the overall
      weighted mean difference (WMD). RESULTS: Twelve studies (n = 1,871: 923 patients
      in the ACL-injured group and 938 patients in the control group) were included.
      The medial tibial plateau slope in the ACL group ranged from 1.8 degrees  +/- 3.7
      degrees  to 12.1 degrees  +/- 3.3 degrees  while it ranged from 2.9 degrees  +/-
      2.8 degrees  to 9.5 degrees  +/- 3 degrees  among the controls. The lateral
      tibial plateau slope in the ACL ranged from 1.8 degrees  +/- 3.2 degrees  to 11.5
      degrees  +/- 3.5 degrees  and 0.3 degrees  +/- 3.6 degrees  to 9 degrees  +/- 4
      degrees  in the control group. Statistically significant increased angles were
      observed in ACL-injured group compared to control group for medial tibial plateau
      slope (WMD, 1.1 degrees ; 95 % confidence interval, 0.5 degrees -1.7 degrees )
      and lateral tibial plateau slope (WMD, 1.8 degrees ; 95 % confidence interval,
      1.3 degrees -2.3 degrees ). Sensitivity analysis and subgroup analysis proved
      this to be a reliable result. CONCLUSIONS: The current meta-analysis suggests
      that both, increased medial and lateral tibial plateau slopes, are associated
      with increased susceptibility to ACL injury regardless of gender. In addition,
      this study indicates a stronger evidence for lateral tibial plateau slope to be
      associated with ACL injury compared with medial tibial plateau slope due to the
      larger increased angle value and on the basis of consistency among the included
      studies.

PMID- 23114869
TI  - Arthroscopic treatment for acute septic arthritis of the hip joint in adults.
AB  - PURPOSE: The purpose of our study was to evaluate the efficacy and safety of the
      arthroscopic management of septic arthritis of the hip joint. METHODS: From
      October 2009 to October 2010, nine patients with septic arthritis of the hip were
      treated with arthroscopic debridement and drainage and systemic antibiotics
      according to bacterial sensitivity or with empiric antibiotics if no bacteria was
      isolated from the cultures. All patients were placed in the supine position on a
      fracture table, and two or three arthroscopic portals were used. The medical
      records were retrospectively reviewed to determine the efficacy and safety of hip
      arthroscopy for septic arthritis. RESULTS: There were 4 men and 5 women, with a
      mean age of 49.8 years (SD 12.1). No major complication related to arthroscopy of
      the hip was encountered. Staphylococcus aureus was identified in 4 patients.
      Average follow-up was 19.4 months (SD 4.1). Septic arthritis relapsed in one
      patient, but the other 8 patients experienced no recurrence during the follow-up
      period. CONCLUSIONS: Arthroscopic lavage and debridement is a safe and effective
      procedure for septic arthritis of the hip joint.

PMID- 23114870
TI  - Custom-fit minimally invasive total knee arthroplasty: effect on blood loss and
      early clinical outcomes.
AB  - PURPOSE: Recently, new custom-fit pin guides in total knee arthroplasty (TKA)
      have been introduced. Use of these guides may reduce operating time. Use of the
      guides combined with the absence of intramedullary alignment jigs may lead to
      reduced blood loss and improved early outcomes. Our aim was to evaluate blood
      loss and early clinical outcomes in patients undergoing minimally invasive TKA
      using custom-fit magnetic resonance imaging (MRI)-based pin guides. METHODS: A
      prospective study in 80 patients was carried out. Patients were divided randomly
      into 2 equal groups. In one group, intramedullary alignment jigs were used. In
      the second group, custom-fit MRI-based pin guides were used. All patients
      received the same cemented posterior-stabilized implant through a mini-midvastus
      approach. The volume in the drain bottles was recorded after 48 h. Hb loss was
      estimated by subtracting the postoperative from the preoperative Hb level.
      Transfusion requirements and surgical time were recorded. Outcome measures were
      Knee Society Scores (KSS), knee flexion, knee swelling and pain. RESULTS: There
      was lower mean drainage of blood in the custom-fit group (391 ml vs. 603 ml; p <
      0.0001). There was no difference in estimated loss of Hb (3.6 g/dl vs. 4.1 g/dl;
      n.s.) and in transfusion requirements (7.5 % vs. 10 %; n.s.). Surgical time was
      reduced in the custom-fit group (12 min less; p = 0.001). KSS measured at week 2,
      6 and 12 showed no significant difference between groups. Knee flexion measured
      on days 7, 10 and at week 6, 12 and knee swelling and pain measured on days 1, 3,
      10 and at week 6, 12 showed no significant difference between groups.
      CONCLUSIONS: Using custom-fit pin guides reduces blood drainage, but not the
      estimated Hb loss in minimally invasive TKA and does not affect transfusion rate.
      Surgical time is reduced. There is no effect on the early clinical outcomes.
      LEVEL OF EVIDENCE: Therapeutic study, Level I.

PMID- 23114871
TI  - Ovarian cancer cells, not normal cells, are damaged by Mirk/Dyrk1B kinase
      inhibition.
AB  - Prior studies had shown that the Mirk/dyrk1B gene is amplified/upregulated in
      about 75% of ovarian cancers, that protein levels of this kinase are elevated in
      quiescent G0 cells and that Mirk maintains tumor cells in quiescence by
      initiating rapid degradation of cyclin D isoforms and by phosphorylation of a
      member of the DREAM complex. Depletion of Mirk/dyrk1B led to increased cyclin D
      levels, an elevated reactive oxygen species (ROS) content and loss of viability.
      However, many normal cells in vivo are quiescent, and therefore, targeting a
      kinase found in quiescent cells might be problematic. In our study, Mirk kinase
      activity was found to be higher in ovarian cancer cells than in normal cells.
      Pharmacological inhibition of Mirk/dyrk1B kinase increased cyclin D levels both
      in quiescent normal diploid cells and in quiescent CDKN2A-negative ovarian cancer
      cells, but led to more active CDK4/cyclin D complexes in quiescent ovarian cancer
      cells, allowing them to escape G0/G1 quiescence, enter cycle with high ROS levels
      and undergo apoptosis. The ROS scavenger N-acetyl cysteine reduced both the
      amount of cleaved poly(ADP-ribose) polymerase (PARP) and the extent of cancer
      cell loss. In contrast, normal cells were spared because of their expression of
      cyclin directed kinase (CDK) inhibitors that blocked unregulated cycling.
      Quiescent early passage normal ovarian epithelial cells and two strains of
      quiescent normal diploid fibroblasts remained viable after the inhibition of
      Mirk/dyrk1B kinase, and the few cells that left G0/G1 quiescence were accumulated
      in G2+M. Thus, inhibition of Mirk kinase targeted quiescent ovarian cancer cells.

PMID- 23114873
TI  - Ubiquitin E3 ligase TNFIAP3 mediates endosome/lysosome fusion in nasal epithelial
      cells.
AB  - The nasal epithelial barrier dysfunction is associated with the pathogenesis of
      nasal allergy; the causative factors are to be further elucidated. Ubiquitin E3
      ligase TNFIAP3 (TNFIAP3, in short) plays a role in the maintenance of the
      homeostasis in the body. This study aims to elucidate the role of TNFIAP3 in the
      degradation of endocytic substances in nasal epithelial cells. The nasal
      epithelial cell line, RPMI 2650 cells (RPC), was cultured into monolayers in
      transwells. The endocytosis of staphylococcal enterotoxin B (SEB) by RPC
      monolayers was assessed by enzyme-linked immunoassay. The endocytosis of SEB
      triggered endosome/lysosome fusion was observed by immunocytochemistry. The
      results showed that RPC monolayers expressed TNFIAP3 upon the endocytosis of SEB.
      Deficiency of TNFIAP3 resulted in abundant SEBs being transported to the basal
      chambers of transwells via the intracellular pathway. In the TNFIAP3-sufficient
      RPC, SEB-carrying endosomes fused with lysosomes were observed. The TNFIAP3
      deficient RPC showed few SEB-carrying endosomes fused with lysosomes. In summary,
      TNFIAP3 plays an important role in tethering endosomes to lysosomes in RPC.

PMID- 23114874
TI  - Tell me a tale of TALEs.
AB  - Pathogenic bacteria of the Xanthomonas and Ralstonia genus have developed
      resourceful strategies creating a favorable environment to multiply and colonize
      their host plants. One of these strategies involves the secretion and
      translocation of several families of effector proteins into the host cell. The
      transcription activator-like effector (TALE) family forms a subset of proteins
      involved in the direct modulation of host gene expression. TALEs include a number
      of tandem 34-amino acid repeats in their central part, where specific residues
      variable in two adjacent positions determine DNA-binding in the host genome. The
      specificity of this binding and its predictable nature make TALEs a revolutionary
      tool for gene editing, functional analysis, modification of target gene
      expression, and directed mutagenesis. Several examples have been reported in
      higher organisms as diverse as plants, Drosophila, zebrafish, mouse, and even
      human cells. Here, we summarize the functions of TALEs in their natural context
      and the biotechnological perspectives of their use.

PMID- 23114872
TI  - Targeting glutamate receptors to tackle the pathogenesis, clinical symptoms and
      levodopa-induced dyskinesia associated with Parkinson's disease.
AB  - The appearance of levodopa-induced dyskinesia (LID) and ongoing degeneration of
      nigrostriatal dopaminergic neurons are two key features of Parkinson's disease
      (PD) that current treatments fail to address. Increased glutamate transmission
      contributes to the motor symptoms in PD, to the striatal plasticity that
      underpins LID and to the progression of neurodegeneration through excitotoxic
      mechanisms. Glutamate receptors have therefore long been considered as potential
      targets for pharmacological intervention in PD, with emphasis on either blocking
      activation of 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic acid (AMPA), N
      methyl-D-aspartate (NMDA) or excitatory metabotropic glutamate (mGlu) 5 receptors
      or promoting the activation of group II/III mGlu receptors. Following a brief
      summary of the role of glutamate in PD and LID, this article explores the current
      status of pharmacological studies in pre-clinical rodent and primate models
      through to clinical trials, where applicable, that support the potential of
      glutamate-based therapeutic interventions. To date, AMPA antagonists have shown
      good efficacy against LID in rat and primate models, but the failure of
      perampanel to lessen LID in clinical trials casts doubt on the translational
      potential of this approach. In contrast, antagonists selective for NR2B
      containing NMDA receptors were effective against LID in animal models and in
      small-scale clinical trials, though observed adverse cognitive effects need
      addressing. So far, mGlu5 antagonists or negative allosteric modulators (NAMs)
      look set to become the first introduced for tackling LID, with AFQ-056 reported
      to exhibit good efficacy in phase II clinical trials. NR2B antagonists and mGlu5
      NAMs may subsequently prove to also be effective disease-modifying agents if
      their protective effects in rat and primate models of PD, respectively, are
      replicated in the next stages of investigation. Finally, group III mGlu4 agonists
      or positive allosteric modulators (PAMs), although in the early pre-clinical
      stages of investigation, are showing good efficacy against motor symptoms,
      neurodegeneration and LID. It is anticipated that the recent development of mGlu4
      PAMs with improved systemic bioavailability will facilitate progression of these
      agents into the primate model of PD where their potential can be further
      explored.

PMID- 23114876
TI  - Increased circulating High-Sensitivity Troponin T concentrations in children and
      adolescents with obesity and the metabolic syndrome: a marker for early cardiac
      damage?
AB  - OBJECTIVE: Childhood obesity is associated with an increased risk for
      atherosclerosis mediated by the pathogenetic mechanisms that lead to the
      development of the Metabolic Syndrome (MetS). High-Sensitivity Troponin T (hs
      TnT) is a specific marker of ischemic myocardial damage, whereas a minimal
      elevation of this biomarker has been found in adults with a high-risk for
      cardiovascular disease. We hypothesized that hs-TnT might be altered in obese
      children with and/or without the Mets. MATERIALS AND METHODS: Fifty-seven (34
      males) obese and 25 non-obese (6 males) children were assessed at the Childhood
      Obesity Clinic of our department. Obesity was defined using the IOTF criteria.
      Metabolic syndrome was defined with the IDF criteria. Hs-TnT was measured using
      an electrochemiluminescence-based assay. RESULTS: The entire group of obese
      children had significantly higher hs-TnT concentrations [4.1 +/- 3.4 ng/L]
      (p=0.029) than the non-obese ones [3.0 +/- 0.2 ng/L), however, in both groups the
      levels of the cardiac biomarker were within the normal range. Comparison of the
      obese children with or without the MetS and the non-obese, revealed that those
      with the MetS had significantly higher hs-TnT (6.7+/-7.1 ng/L) than the obese
      without MetS (3.7 +/- 2.1 ng/L) [p=0.044], and the non-obese [p=0.014]. Hs-TnT
      did not differ between the obese without MetS and the non-obese. CONCLUSIONS:
      Circulating concentrations of hs-TnT in obese children with the MetS are higher
      than those of the obese without the MetS and the non-obese, suggesting that it is
      obesity-related metabolic changes rather than obesity per se linked to increased
      hs-TnT in children.

PMID- 23114877
TI  - Clinicopathological review of pallidonigroluysian atrophy.
AB  - Pallidonigroluysian atrophy is a rare neurodegenerative disease characterized by
      degeneration of the globus pallidus, substantia nigra, and subthalamic nucleus.
      Few studies have comprehensively documented the clinical and pathological
      features of pallidonigroluysian atrophy. A systematic review of all published
      cases of pallidonigroluysian atrophy in English since 1970 was performed. We also
      report a new case of pallidonigroluysian atrophy. Twenty-five cases of
      pathologically proven pallidonigroluysian atrophy were reviewed, 24 from the
      literature and 1 of our own. Average age of onset was 54.3 +/- 14.3 years, and
      average duration of disease was 7.9 +/- 5.8 years. The most common first symptom
      was gait or balance disturbance. Patients had a diversity of movement disorders,
      including chorea in 5 cases (20%). Nine cases (36%) had coexistent motor neuron
      disease. Almost all cases had gliosis, and many cases had iron-positive pigments
      in the pallidonigroluysian system. Tauopathy was absent to rare in this region.
      Widespread tau-negative, p62-positive glial inclusions, described in 1 previous
      case, were also present in our patient. As pallidonigroluysian atrophy has a
      diversity of clinical presentations, it is best defined neuropathologically. The
      relative lack of tauopathy and the presence of p62-positive glial inclusions or
      iron-positive pigments in the pallidonigroluysian region may help to distinguish
      pallidonigroluysian atrophy from similar disease entities.

PMID- 23114878
TI  - Patient specific proteolytic activity of monocyte-derived macrophages and
      osteoclasts predicted with temporal kinase activation states during
      differentiation.
AB  - Patient-to-patient variability in disease progression continues to complicate
      clinical decisions of treatment regimens for cardiovascular diseases, metastatic
      cancers and osteoporosis. Here, we investigated if monocytes, circulating white
      blood cells that enter tissues and contribute to disease progression by
      differentiating into macrophages or osteoclasts, could be useful in understanding
      this variability. Monocyte-derived macrophages and osteoclasts produce cysteine
      cathepsins, powerful extracellular matrix proteases which have been
      mechanistically linked to accelerated atherosclerotic, osteoporotic, and tumor
      progression. We hypothesized that multivariate analysis of temporal kinase
      activation states during monocyte differentiation could predict cathepsin
      proteolytic responses of monocyte-derived macrophages and osteoclasts in a
      patient-specific manner. Freshly isolated primary monocytes were differentiated
      with M-CSF or RANKL into macrophages or osteoclasts, respectively, and
      phosphorylation of ERK1/2, Akt, p38 MAPK, JNK, c-jun, and IkappaB-alpha were
      measured at days 1, 3, 6, and 9. In parallel, cell diameters and numbers of
      nuclei were measured, and multiplex cathepsin zymography was used to quantify
      cathepsins K, L, S, and V activity from cell extracts and conditioned media.
      There was extensive patient-to-patient variability in temporal kinase activation
      states, cell morphologies, and cathepsin K, L, S, and V proteolytic activity.
      Partial least squares regression models trained with temporal kinase activation
      states successfully predicted patient-specific morphological characteristics
      (mean cell diameter and number of nuclei) and patient-specific cathepsin
      proteolytic activity with predictability as high as 95%, even with the challenge
      of incorporating the complex, unknown cues from individual patients' unique
      genetic and biochemical backgrounds. This personalized medicine approach
      considers patient variability in kinase signals to predict cathepsin activity.
      Such analyses may provide beneficial tools for personalized kinase and protease
      inhibitor therapies for tissue destructive diseases.

PMID- 23114879
TI  - Incidence of bisphosphonate-related osteonecrosis of the jaws (BRONJ) in patients
      taking bisphosphonates for osteoporosis treatment - a grossly underestimated
      risk?
AB  - PURPOSE: The aim of this study was to detect the incidence of bisphosphonate
      related osteonecrosis of the jaws (BRONJ) in association with osteoporosis in
      2009 in the rural district of Marburg-Biedenkopf, Germany. In addition, the
      therapeutic regimen of dentists in this area was compared to the treatment
      guidelines of established international associations. METHODOLOGY: A postal
      survey including 129 dental offices within the named investigation area was
      conducted. Additionally, the dentists were asked to contribute to this study
      during a course of retraining. Ultimately, 107 colleagues participated in this
      study. RESULTS: A total of 37 BRONJ cases were revealed, 37.4 % of those were
      linked to malignant diseases, 62.6 % to osteoporosis. Noticeably, 30.1 % of the
      BRONJ cases linked to osteoporosis were connected with intravenous application.
      In total, 62.6 % of all cases were associated with intravenous and 37.4 % with
      oral application. Considering the estimated number of 1.014 patients using
      bisphosphonates for osteoporosis treatment in Marburg-Biedenkopf in 2009, the
      specific incidence of BRONJ could be narrowed down to about 2.27 %. In proportion
      to the increasing risk potential of the three patient groups, participants
      conducted fewer surgical interventions themselves but tended to refer patients to
      colleagues. CONCLUSION: This study reveals the incidence of BRONJ in association
      with osteoporosis as being grossly underrated so far, especially in connection
      with intravenous bisphosphonate treatment. The therapeutic regimen of the
      dentists who participated correlated with the established guidelines. CLINICAL
      RELEVANCE: The interface between dentistry and medicine may profit from our
      study's results which will help to improve interdisciplinary communication. With
      regard to this, we wish to contribute to an informative discussion since a main
      focus was to ensure colleagues in their decision making, especially in case of
      complications after elective dentoalveolar surgery-like implantations. Besides
      medical there are also economic and political aspects, i.e. the financial
      responsibility in case of unexpected or inevitable complications, possibly
      leading to BRONJ, that may become part of future discussions based on this study.

PMID- 23114880
TI  - Comparative micro-computed tomographic evaluation of two carrier-based obturation
      systems.
AB  - OBJECTIVES: The aim of the study was to measure the percentage of volume of voids
      and gaps in the apical third of root canals obturated with two techniques using
      micro-computed tomography. MATERIALS AND METHODS: Fifty-four single-rooted teeth
      were collected and root canal-prepared. The roots were randomly allocated into
      two groups; each group was obturated by using thermoplasticized technique with a
      different material (gutta-percha and Topseal for Thermafil, Resilon and RealSeal
      for RealSeal 1). Roots were then scanned, and volume measurements for voids and
      gaps in the obturated roots were carried out using specialized CT software.
      Percentage of gaps and voids was calculated. RESULTS: The present study showed
      that none of the root canal-filled teeth was gap free. Student t test was
      conducted. No significant difference was found between Thermafil and RealSeal 1
      concerning percentage of voids in the apical third (P > 0.05). Both materials
      showed statistically significant difference between the levels where 1 mm showed
      the highest volume of voids (P < 0.05). CONCLUSIONS: Both carrier-based
      techniques allowed a good sealing ability in root canals but none of the
      materials was gap free. Statistically significant difference between the levels
      was found and 1 mm showed the highest volume of voids. CLINICAL RELEVANCE: This
      study shows the efficiency of carrier-based obturation systems in filling root
      canals hermetically. It compares new adhesive endodontic materials with the
      traditional gold standard gutta-percha. Results show the good sealing ability of
      both techniques making them appropriate to use in daily endodontic obturations.

PMID- 23114881
TI  - Hematocrit, viscosity and velocity distributions of aggregating and non
      aggregating blood in a bifurcating microchannel.
AB  - Microscale blood flow is characterised by heterogeneous distributions of
      hematocrit, viscosity and velocity. In microvascular bifurcations, cells are
      unevenly distributed between the branches, and this effect can be amplified in
      subsequent branches depending on a number of parameters. We propose an approach
      to infer hematocrit profiles of human blood flowing through a bifurcating
      microchannel. The influence of aggregation, induced by the addition of Dextran
      2000 to the samples, is also considered. Averaged values indicate plasma
      skimming, particularly in the presence of red blood cell (RBC) aggregation. Using
      an empirical model, the hematocrit profiles are used to estimate local relative
      viscosity distributions. Simulations are used to predict how the non-uniform
      viscosity influences the velocity profiles. Comparing these data to velocity
      profiles of RBCs measured using particle image velocimetry provides validation of
      the model. It is observed that aggregation blunts velocity profiles after a long
      straight section of channel. Downstream of the bifurcation, skewing of the
      velocity profiles is detected, which is enhanced by aggregation. The proposed
      methodology is capable of providing hitherto unreported information on important
      aspects of microscale blood rheology. 

PMID- 23114882
TI  - Direct progression of capsular invasive carcinomas from subcapsular focal
      hyperplasias induced by hypothyroidism-mediated tumor promotion in a rat two
      stage thyroid carcinogenesis model.
AB  - PURPOSE: Some goitrogens promote thyroid carcinogenesis in rats in an initiation
      promotion model; this model frequently produces carcinomas that invade fibrously
      thickened capsules, termed capsular invasive carcinomas (CICs). The present study
      tested a hypothesis that CICs originate from parenchymal proliferative lesions
      located beneath the capsule. METHODS: Cell proliferation activity, cell-cycle
      kinetics and cellular invasion were immunohistochemically examined in subcapsular
      proliferative lesions in male F344 rats treated with an anti-thyroid agent,
      propylthiouracil or sulfadimethoxine, during the tumor-promotion phase after
      initiation with N-bis(2-hydroxypropyl)nitrosamine. RESULTS: Focal follicular cell
      hyperplasias (FFCHs) were the most commonly observed parenchymal proliferative
      lesions. Subcapsular FFCHs located near CICs showed more Ki-67(+) cells in the
      capsular side than the contrary parenchymal center side. Most of these FFCHs
      located near CICs showed accumulated immunoreactivity for cyclin A, cyclin D,
      cyclin E and cyclin-dependent kinase-2, whereas most subcapsular FFCHs located
      elsewhere did not show such accumulated expression of cell-cycle molecules.
      Subcapsular FFCHs immunoreactive at the capsular front for tenascin-C, a tumor
      invasion marker of extracellular matrix protein, showed high proliferation
      activity. CONCLUSIONS: Subcapsular FFCH-forming cells can potentially spread
      directly into the fibrously thickened capsule to form CICs by accelerating cell
      cycle activity.

PMID- 23114883
TI  - Routine pelvic MRI using phased-array coil for detection of extraprostatic tumour
      extension: accuracy and clinical significance.
AB  - OBJECTIVES: To determine the accuracy and assess the clinical significance of
      surface-coil 1.5-T magnetic resonance imaging (MRI) for the detection of locally
      advanced prostate cancer (PCa). METHODS: Between December 2007 and January 2010,
      we examined 209 PCa patients (mean age = 62.5 years) who were consecutively
      treated with robot-assisted laparoscopic prostatectomy and prospectively staged
      by MRI. One hundred and thirty-five patients (64.6 %) had locally advanced
      disease. Conventional clinical tumour stage and MRI-assessed tumour stage were
      compared with histopathological tumour stage (pT). Sensitivity, specificity,
      positive predictive value (PPV), negative predictive value (NPV) and overall
      accuracy (OA) were calculated using pT as the "gold standard". Overstaged and
      understaged cases at MRI were reviewed. RESULTS: Sensitivity, specificity, PPV,
      NPV and OA for the detection of locally advanced disease were 25.9, 95.9, 92.1,
      41.2 and 50.5 % and 56.3, 82.2, 85.4, 50.4 and 65.4 % for clinical staging and
      MRI, respectively. Among patients understaged at MRI, the resection margins were
      free in 64.4 % of the cases (38/59). CONCLUSIONS: Although the accuracy was
      limited, the detection of locally advanced disease improved substantially when
      MRI was added to routine clinical staging. The majority of the understaged
      patients nevertheless achieved free margins. When assessing the clinical
      significance of MRI staging the extent of extraprostatic extension has to be
      considered.

PMID- 23114884
TI  - Brain atrophy associations with white matter lesions in the ageing brain: the
      Lothian Birth Cohort 1936.
AB  - OBJECTIVE: Cerebral atrophy and white matter lesions (WMLs) are common in older
      people with common risk factors, but it is unclear if they are related. We
      investigated whether and to what degree they are related in deep and superficial
      structures using both volumetric and visual ratings. METHODS: The intracranial,
      total brain tissue (TBV), cerebrospinal fluid (CSF), ventricular superficial
      subarachnoid space (SSS), grey matter, normal-appearing white matter, WMLs, and
      combined CSF, venous sinuses and dural volumes were measured. WMLs were also
      rated using the Fazekas scale. RESULTS: Amongst 672 adults (mean age 73 +/- 1
      years), WMLs were associated with global brain atrophy (TBV, beta = -0.43 mm(3),
      P < 0.01) and specifically with deep (ventricular enlargement, beta = 0.10 mm(3),
      P = 0.03) rather than superficial (SSS, beta = 0.09 mm(3), P = 0.55) atrophy. A 1
      mm(3) increase in WML volume was associated with a 0.43 mm(3) decrease in TBV and
      0.10 mm(3) increase in ventricular volume. WMLs were associated with combined CSF
      + Venous Sinuses + Meninges volumes, but not CSF volume alone. Some of the
      associations were attenuated after correcting for vascular risk factors. The
      associations were similar for visually scored WMLs. CONCLUSION: WMLs are
      associated with brain atrophy, primarily with deep brain structures. Measures of
      brain atrophy should include all intracranial structures when assessing brain
      shrinkage.

PMID- 23114885
TI  - Targeting activation of specific NF-kappaB subunits prevents stress-dependent
      atherothrombotic gene expression.
AB  - Psychosocial stress has been shown to be a contributing factor in the development
      of atherosclerosis. Although the underlying mechanisms have not been elucidated
      entirely, it has been shown previously that the transcription factor nuclear
      factor-kappaB (NF-kappaB) is an important component of stress-activated signaling
      pathway. In this study, we aimed to decipher the mechanisms of stress-induced NF
      kappaB-mediated gene expression, using an in vitro and in vivo model of
      psychosocial stress. Induction of stress led to NF-kappaB-dependent expression of
      proinflammatory (tissue factor, intracellular adhesive molecule 1 [ICAM-1]) and
      protective genes (manganese superoxide dismutase [MnSOD]) via p50, p65 or cRel.
      Selective inhibition of the different subunits and the respective kinases showed
      that inhibition of cRel leads to the reduction of atherosclerotic lesions in
      apolipoprotein(-/-) (ApoE(-/-)) mice via suppression of proinflammatory gene
      expression. This observation may therefore provide a possible explanation for
      ineffectiveness of antioxidant therapies and suggests that selective targeting of
      cRel activation may provide a novel approach for the treatment of stress-related
      inflammatory vascular disease.

PMID- 23114886
TI  - Is there a role for high mobility group box 1 and the receptor for advanced
      glycation end products in the genesis of long-term cognitive impairment in sepsis
      survivors?

PMID- 23114888
TI  - Wnt/beta-catenin and its diverse physiological cell signaling pathways in
      neurodegenerative and neuropsychiatric disorders.
AB  - Wnt signaling is a fundamental pathway in embryogenesis which is evolutionary
      conserved from metazoans to humans. Much of our understanding of Wnt signaling
      events emerged from key developmental studies in drosophila, zebra fish, xenopus,
      and mice. Considerable data now exists on the role of Wnt signaling beyond these
      developmental processes and in particular its role in health and disease. The
      focus of this special issue is on Wnt/beta-catenin and its diverse physiological
      cell signaling pathways in neurodegenerative and neuropsychiatric disorders. This
      special issue is composed of six reviews and two original articles selected to
      highlight recent advances in the role of Wnt signaling in CNS embryonic
      development, in adult brain function, in neurodegenerative conditions such as
      Alzheimer's disease, schizophrenia, NeuroAIDS, and in gliomas. The finding that
      beta-catenin can translocate to the nucleus where it binds to TCF/LEF
      transcription factors to regulate target gene expression was a seminal
      observation that linked beta-catenin/LEF to T cell development and
      differentiation. We also provide a nostalgic look on recent advances in role of
      Wnts in T cell development and maturation. These reviews highlight the extensive
      body of work in these thematic areas as well as identify knowledge gaps, where
      appropriate. Understanding Wnt function under healthy and diseased conditions may
      provide a therapeutic resource, albeit it a challenging one, in diseases where
      dysfunctional and/or diminished Wnt signaling is a prominent player in the
      disease process.

PMID- 23114890
TI  - Why don't women participate? A qualitative study on non-participation in a
      surgical randomised controlled trial.
AB  - INTRODUCTION AND HYPOTHESIS: The objective of the study was to identify reasons
      why women declined participation in a pilot randomised controlled trial (RCT)
      comparing tension-free vaginal tape (TVT) under general anaesthetic (GA) with
      single incision sling (SIS) under local anaesthetic (LA). These data would inform
      the design of a larger trial to improve patient recruitment. METHODS: This was a
      qualitative interview study on women eligible to have a TVT for stress urinary
      incontinence in a tertiary referral hospital in the UK. Women were counselled in
      a standardised manner. They were informed that the short-term success rates were
      similar for both operations. Women who declined to take part in the RCT were
      interviewed using a topic guide. Themes and sub-themes on non-participation were
      identified by two independent observers using a constant comparison method.
      RESULTS: Twenty-three non-participants of the RCT were interviewed. Common themes
      for non-participation were a preference for TVT and request for GA. Sub-themes
      showed that the TVT was preferred due to its perceived better efficacy as well as
      a minimal benefit from a SIS and also an unwillingness to take unknown risks. GA
      was favoured due to fear of local awareness, past negative experiences and
      embarrassment. Additional tests and follow-up visits were not cited as a reason
      for non-participation. CONCLUSIONS: The study found that non-participants are not
      research averse in general but they had strong preferences about specific aspects
      of treatment. Risk propensity and personality may also influence this behaviour.
      The study also demonstrates how a qualitative pilot study may improve trial
      design.

PMID- 23114891
TI  - Newer innovations in treatment of retracted nipple.
AB  - OBJECTIVES: To compare the efficacy, merits and demerits of various methods for
      the treatment of retracted nipple, i.e., two new innovative methods (rubber band
      method and sucking by the husband) with the in-use syringe method. METHODS: A
      prospective study on 213 women having retracted nipple, 71 in each of the three
      groups was carried out. Group A included patients in which syringe method was
      used; Group B comprised of woman in which rubber band method was used and Group C
      included patients with vigorous sucking by the husband. RESULTS: Highest success
      rates were seen in Group C (vigorous sucking by the husband), being 52, 88 and 94
      % on days 3, 7 and 14 respectively. Success rates in Group B (rubber band method)
      were lower, being 43, 66 and 74 % respectively and lowest in Group A (syringe
      method), i.e., 33, 47 and 64 %, respectively on corresponding days. Problem of
      difficulty in applying technique were common in Group B (38 %), less common in
      Group A (22 %) and nil in Group C. The incidence of local pain had the same trend
      i.e., 48 and 30 % in Group B and A, respectively, and nil in Group C. Disliking
      taste of milk in mouth and problem of privacy were highest in Group C i.e., 28 %
      and 100 % respectively. CONCLUSIONS: Although syringe method is well established,
      sucking by husband is definitely superior and a boon for difficult cases too.
      Rubber band method is a bit inferior due to complicated technique, local pain and
      no lactation stimulation.

PMID- 23114889
TI  - Immune heterogeneity in neuroinflammation: dendritic cells in the brain.
AB  - Dendritic cells (DC) are critical to an integrated immune response and serve as
      the key link between the innate and adaptive arms of the immune system. Under
      steady state conditions, brain DC's act as sentinels, continually sampling their
      local environment. They share this function with macrophages derived from the
      same basic hemopoietic (bone marrow-derived) precursor and with parenchymal
      microglia that arise from a unique non-hemopoietic origin. While multiple cells
      may serve as antigen presenting cells (APCs), dendritic cells present both
      foreign and self-proteins to naive T cells that, in turn, carry out effector
      functions that serve to protect or destroy. The resulting activation of the
      adaptive response is a critical step to resolution of injury or infection and is
      key to survival. In this review we will explore the critical roles that DCs play
      in the brain's response to neuroinflammatory disease with emphasis on how the
      brain's microenvironment impacts these actions.

PMID- 23114892
TI  - Management of Shiga toxin-associated Escherichia coli-induced haemolytic uraemic
      syndrome: randomized clinical trials are needed.

PMID- 23114893
TI  - Pulmonary hypertension in dialysis patients: a prevalent, risky but still
      uncharacterized disorder.

PMID- 23114894
TI  - Expect the unexpected in the cell therapy of renal ischaemia.

PMID- 23114895
TI  - Inhibitors/antagonists of TGF-beta system in kidney fibrosis.
AB  - Renal fibrosis is a major hallmark of chronic kidney disease, regardless of the
      initial causes, and prominent renal fibrosis predicts poor prognosis for renal
      insufficiency. Transforming growth factor (TGF)-beta plays a pivotal role in the
      progression of renal fibrosis, and therapeutic interventions targeting TGF-beta
      have been successful and well tolerated in animal models. However, these
      interventions might have adverse effects by inducing systemic inflammation due to
      the strong bifunctional role of TGF-beta (pro-fibrotic and anti-inflammatory).
      This review of the current literature focuses on the inhibitors/antagonists of
      TGF-beta, and discusses possible therapeutic approaches targeting them,
      describing the effectiveness of orally active bone morphogenetic protein 7
      mimetics in reversing established fibrosis. It will conclude with a brief
      discussion of possible future directions for research.

PMID- 23114896
TI  - Genetic causes and mechanisms of distal renal tubular acidosis.
AB  - The primary or hereditary forms of distal renal tubular acidosis (dRTA) have
      received increased attention because of advances in the understanding of the
      molecular mechanism, whereby mutations in the main proteins involved in acid-base
      transport result in impaired acid excretion. Dysfunction of intercalated cells in
      the collecting tubules accounts for all the known genetic causes of dRTA. These
      cells secrete protons into the tubular lumen through H(+)-ATPases functionally
      coupled to the basolateral anion exchanger 1 (AE1). The substrate for both
      transporters is provided by the catalytic activity of the cytosolic carbonic
      anhydrase II (CA II), an enzyme which is also present in the proximal tubular
      cells and osteoclasts. Mutations in ATP6V1B1, encoding the B-subtype unit of the
      apical H(+) ATPase, and ATP6V0A4, encoding the a-subtype unit, lead to the loss
      of function of the apical H(+) ATPase and are usually responsible for patients
      with autosomal recessive dRTA often associated with early or late sensorineural
      deafness. Mutations in the gene encoding the cytosolic CA II are associated with
      the autosomal recessive syndrome of osteopetrosis, mixed distal and proximal RTA
      and cerebral calcification. Mutations in the AE1, the gene that encodes the Cl(
      )/HCO(3)(-) exchanger, usually present as dominant dRTA, but a recessive pattern
      has been recently described. Several studies have shown trafficking defects in
      the mutant protein rather than the lack of function as the major mechanism
      underlying the pathogenesis of dRTA from AE1 mutations.

PMID- 23114897
TI  - Myeloma kidney: advances in molecular mechanisms of acute kidney injury open
      novel therapeutic opportunities.
AB  - Renal impairment is a common complication of multiple myeloma (MM) and is
      supported in virtually all patients by a tubulointerstitial pathology that
      results from high serum concentrations of monoclonal free light chains (FLCs).
      The proteins involved in the kidney injury and the analysis of their binding
      interactions have been thoroughly investigated and the main pathogenic mechanisms
      are being elucidated. Early sustained reduction of circulating FLC leads to
      improved renal recovery rates that translate into improved quality of life and
      survival. The mainstay of therapy is presently the removal of aggravating factors
      (dehydration, hypercalcaemia, nephrotoxic drugs) and the prompt institution of
      rapidly acting novel chemotherapy combinations. This approach allows the rescue
      of kidney function in more than two-thirds of patients. High cut-off
      haemodialysis dialysers may potentially add clinical benefits and the outcomes of
      controlled trials are eagerly awaited. Basic research findings have led to the
      design of targeted drugs that prevented the functional manifestations of acute
      kidney injury in animal models. There is now hope to prevent the renal damage in
      patients with MM.

PMID- 23114898
TI  - Should patients with advanced chronic kidney disease and atrial fibrillation
      receive chronic anticoagulation?
AB  - Atrial fibrillation is prevalent in dialysis patients. Both ischaemic and
      haemorrhagic stroke are common in patients on dialysis with atrial fibrillation.
      In the general population, warfarin is highly effective for prophylaxis of
      ischaemic stroke, and though warfarin use likely increases the risk of
      intracranial haemorrhage, the absolute increase in risk is small. In the general
      population, absolute and relative increases in major extracranial bleeding from
      warfarin use are also both modest. In patients on dialysis, the effectiveness of
      warfarin as a prophylaxis for ischaemic stroke and its effects on intracranial or
      extracranial bleeding have not been assessed in randomized trials. Cohort studies
      vary greatly in their estimates of the magnitude of the increased risk of
      bleeding from warfarin use. A single cohort study found rates of intracranial
      haemorrhage in patients on dialysis with atrial fibrillation to be in an order of
      magnitude that is greater than those in the general population with atrial
      fibrillation, and that intracranial haemorrhage more than doubled in association
      with warfarin use. Basic, translational and limited clinical observations also
      implicate warfarin in the pathogenesis of vascular calcification, which is likely
      on the causal pathway to patient-important vascular outcomes. Finally, the effect
      of warfarin on ischaemic stroke in three recent large observational studies has
      been in the direction of harm, no benefit, and modest, non-statistically
      significant benefit, respectively. We believe that no clear recommendation can be
      made between three alternative approaches. It is acceptable to withhold or
      discontinue warfarin in patients on dialysis, to offer anticoagulants to all
      dialysis patients without a contraindication whose congestive heart failure,
      hypertension, age, diabetes and previous stroke or transient ischaemic attack
      (CHADS(2)) score >1 or 2 and to discuss and individualize prophylaxis on a
      patient-by-patient basis. Randomized trials of new agents are needed in this
      area.

PMID- 23114900
TI  - Transplantation in the obese: separating myth from reality.
AB  - The prevalence of obesity among patients requiring renal replacement therapy
      continues to increase inexorably. While observational data have suggested that
      obesity may be associated with better outcomes among patients on dialysis, many
      centres have been reluctant to transplant obese patients because of concerns over
      adverse outcomes in the short and long term. In this review, we evaluate data
      about the safety of weight loss on dialysis and critically review the impact of
      pre-transplant body mass index and sarcopenia on post-transplant outcomes. We
      also highlight comparative data on outcomes of obese patients on dialysis versus
      those undergoing kidney transplantation. We conclude that while obesity can
      increase the risk of complications such as wound infections or delayed graft
      function, selected obese patients can achieve good outcomes after transplantation
      with the risk being broadly comparable to other recipient co-morbidities such as
      diabetes mellitus.

PMID- 23114899
TI  - Is chronic hyponatremia a novel risk factor for hip fracture in the elderly?
AB  - Hip fractures represent a serious health risk in the elderly, with significant
      associated morbidity and mortality. There is now an emerging literature that
      suggests that chronic hyponatremia increases the adjusted odds ratio (OR) for
      both falls and fractures in the elderly. Hyponatremia appears to contribute to
      falls and fractures by two mechanisms: (i) it produces mild cognitive impairment
      resulting in unsteady gait and falls and (ii) it directly contributes to
      osteoporosis and increased bone fragility by inducing increased bone resorption
      to mobilize sodium. There is debate over the effect of hyponatremia on the
      production of osteoporosis, as one study found decreased bone mineral density
      (BMD) and another did not. Should we be screening for low serum sodium in
      patients with osteoporosis or assessing BMD in patients with hyponatremia? The
      final answer is yet to come from prospective studies that allocate elderly
      individuals with mild hyponatremia to receive active treatment or not for
      hyponatremia and see if this intervention prevents gait disturbances and changes
      in BMD reducing fracture risk. In the meantime, physicians caring for elderly
      patients must be aware of the association between hyponatremia and bone problems.
      As serum sodium is a readily available, simple and affordable biochemical
      measurement, clinicians should look for hyponatremia in elderly patients who take
      medications that can cause hyponatremia. Also, elderly patients with unsteady
      gait and/or confusion should be checked for the presence of mild hyponatremia and
      if present it should not be ignored. Finally, elderly patients presenting with an
      orthopedic injury should have serum sodium checked and corrected if hyponatremia
      is present.

PMID- 23114901
TI  - Diagnosis of cyst infection in patients with autosomal dominant polycystic kidney
      disease: attributes and limitations of the current modalities.
AB  - Cyst infection is a diagnostic challenge in patients with autosomal dominant
      polycystic kidney disease (ADPKD) because of the lack of specific manifestations
      and limitations of conventional imaging procedures. Still, recent clinical
      observations and series have highlighted common criteria for this condition. Cyst
      infection is diagnosed if confirmed by cyst fluid analysis showing bacteria and
      neutrophils, and as a probable diagnosis if all four of the following criteria
      are concomitantly met: temperature of >38 degrees C for >3 days, loin or liver
      tenderness, C-reactive protein plasma level of >5 mg/dL and no evidence for
      intracystic bleeding on computed tomography (CT). In addition, the elevation of
      serum carbohydrate antigen 19-9 (CA19-9) has been proposed as a biomarker for
      hepatic cyst infection. Positron-emission tomography after intravenous injection
      of 18-fluorodeoxyglucose, combined with CT, proved superior to radiological
      imaging techniques for the identification and localization of kidney and liver
      pyocyst. This review summarizes the attributes and limitations of these recent
      clinical, biological and imaging advances in the diagnosis of cyst infection in
      patients with ADPKD.

PMID- 23114902
TI  - Con: on cardiovascular outcomes and the arteriovenous fistula: lesser of evils.

PMID- 23114903
TI  - Best supportive care and therapeutic plasma exchange with or without eculizumab
      in Shiga-toxin-producing E. coli O104:H4 induced haemolytic-uraemic syndrome: an
      analysis of the German STEC-HUS registry.
AB  - BACKGROUND: May 22nd marks the beginning of a Shiga-toxin-producing Escherichia
      coli (STEC) O104:H4 outbreak in Northern Germany. By its end on 27 July, it had
      claimed 53 deaths among 2987 STEC and 855 confirmed haemolytic-uraemic syndrome
      (HUS) cases. METHODS: To describe short-term effectiveness of best supportive
      care (BSC), therapeutic plasma exchange (TPE) and TPE with eculizumab (TPE-Ecu)
      in 631 patients with suspected HUS treated in 84 hospitals in Germany, Sweden and
      the Netherlands using the web-based registry of the DGfN (online since 27 May).
      RESULTS: Of 631 entries, 491 fulfilled the definition of HUS (median age 46
      years; 71% females). The median (inter-quartile range) hospital stay was 22 (14
      31) days. Two hundred and eighty-one (57%) patients underwent dialysis and 114
      (23%) mechanical ventilation. Fifty-seven patients received BSC, 241 TPE and 193
      TPE-Ecu. Treatment strategy was dependent on disease severity (laboratory signs
      of haemolysis, thrombocytopenia, peak creatinine level, need for dialysis,
      neurological symptoms, frequency of seizures) which was lower in BSC than in TPE
      and TPE-Ecu patients. At study endpoint (hospital discharge or death), the median
      creatinine was lower in BSC [1.1 mg/dL (0.9-1.3)] than in TPE [1.2 mg/dL (1.0
      1.5), P < 0.05] and TPE-Ecu [1.4 mg/dL (1.0-2.2), P < 0.001], while need for
      dialysis was not different between BSC (0.0%, n = 0), TPE (3.7%; n = 9) and TPE
      Ecu (4.7%, n = 9). Seizures were absent in BSC and rare in TPE (0.4%; n = 1) and
      TPE-Ecu (2.6%; n = 5) patients. Total hospital mortality in HUS patients was 4.1%
      (n = 20) and did not differ significantly between the TPE and TPE-Ecu groups.
      CONCLUSIONS: Despite frequent renal impairment, advanced neurological disorders
      and severe respiratory failure, short-term outcome was better than expected when
      compared with previous reports. Within the limitations of a retrospective
      registry analysis, our data do not support the notion of a short-term benefit of
      Ecu in comparison to TPE alone in the treatment of STEC-HUS. A randomized trial
      comparing BSC, TPE and Ecu seems to be prudent and necessary prior to
      establishing new treatment guidelines for STEC-HUS.

PMID- 23114904
TI  - Systematic review and meta-analysis of incidence, prevalence and outcomes of
      atrial fibrillation in patients on dialysis.
AB  - BACKGROUND: The reported incidence, prevalence and outcomes of atrial
      fibrillation (AF) in patients with end-stage renal disease (ESRD) are variable.
      The risks and benefits of warfarin anticoagulation need to be defined as the risk
      of bleeding in ESRD patients may overwhelm the benefits of embolic stroke
      prevention. We undertook a systematic literature review to clarify these issues.
      METHODS: A literature search was undertaken using Medline and EMBASE from 1990 to
      September 2011. Studies that reported incidence, prevalence or selected outcomes
      in ESRD patients with AF were included. Cross-sectional, cohort and randomized
      controlled trials with >25 participants were included. The lists of authors and
      abstracts from the search were reviewed by two investigators to determine the
      manuscripts for full text review. Data were abstracted to a form designed
      specifically for this study. The quality of the studies was assessed using the
      Newcastle-Ottawa scale. Event rates were calculated using a random-effects model.
      RESULTS: Twenty-five studies met our inclusion criteria. The prevalence of AF was
      11.6% and the overall incidence was 2.7/100 patient-years. The risk of mortality
      and stroke was increased in ESRD patients with AF at 26.9 and 5.2/100 patient
      years versus 13.4 and 1.9/100 patient-years compared with ESRD patients without
      AF. The majority of studies do not support a protective effect for warfarin in
      ESRD patients with AF. CONCLUSIONS: The incidence and prevalence of AF in ESRD
      patients are higher than in the general population and are associated with an
      increased risk of stroke and mortality. An appropriately designed randomized
      controlled trial is required to determine whether anticoagulation is an
      appropriate therapeutic strategy in patients with end-stage renal disease and
      atrial fibrillation.

PMID- 23114905
TI  - Eotaxin/CCL11 in idiopathic retroperitoneal fibrosis.
AB  - BACKGROUND: Idiopathic retroperitoneal fibrosis (IRF) is a rare fibro
      inflammatory disorder characterized by a periaortic tissue which often encases
      the ureters causing acute renal failure. IRF histology shows fibrosis and a
      chronic inflammatory infiltrate with frequent tissue eosinophilia. We assessed a
      panel of molecules promoting eosinophilia and fibrosis in IRF patients and
      performed an immunogenetic study. METHODS: Serum levels of eotaxin/CCL11,
      regulated and normal T-cell expressed and secreted (RANTES), granulocyte colony
      stimulating factor (G-CSF), interleukin (IL)-5, platelet-derived growth factor
      (PDGF) and fibroblast growth factor (FGF) were measured using a multiplex assay
      in 24 newly diagnosed, untreated IRF patients and 14 healthy controls.
      Retroperitoneal biopsies (available in 8/24 patients) were histologically
      evaluated to assess eosinophil infiltration, whereas mast cells (MCs) were
      identified by immunohistochemical analysis for human tryptase.
      Immunohistochemistry for eotaxin/CCL11 and its receptor CCR3 was also performed.
      Six single nucleotide polymorphisms (SNPs) within the CCL11 gene (rs6505403,
      rs1860184, rs4795896, rs17735961, rs16969415 and rs17809012) were investigated in
      142 IRF patients and 214 healthy controls. RESULTS: Serum levels of eotaxin/CCL11
      were higher in IRF patients than in controls (P = 0.009). Eotaxin/CCL11 drives
      tissue infiltration of eosinophils and MCs, which can promote fibrosis.
      Eosinophilic infiltration was prominent (>5 cells/hpf) in five (62.5%) cases, and
      abundant tryptase-positive MCs were found in all cases; notably, MCs were in a
      degranulating state. Immunohistochemistry showed that CCL11 was highly produced
      by infiltrating mononuclear cells and that its receptor CCR3 was expressed by
      infiltrating eosinophils, MCs, lymphocytes and fibroblasts. None of the tested
      CCL11 SNPs showed disease association, but the TTCCAT haplotype was significantly
      associated with IRF (P = 0.0005). CONCLUSIONS: These findings suggest that the
      eotaxin/CCL11-CCR3 axis is active in IRF and may contribute to its pathogenesis;
      the TTCCAT haplotype within the CCL11 gene is significantly associated with IRF.

PMID- 23114906
TI  - Plasma B-type natriuretic peptide level predicts kidney prognosis in patients
      with predialysis chronic kidney disease.
AB  - BACKGROUND: As a cardiorenal syndrome, there is a dynamic interplay between the
      heart and the kidney. We conducted a prospective study to evaluate the prognostic
      impact of plasma B-type natriuretic peptide (BNP) level, a cardiac biomarker, on
      the long-term kidney prognosis in chronic kidney disease (CKD) patients. METHODS:
      We prospectively enrolled 508 patients with CKD Stages 3, 4 and 5 not on
      dialysis, from a single nephrology department between 2004 and 2010. The
      exclusion criteria were over 90 years of age, malignancy, active infection, low
      cardiac ejection fraction and rapid progressive glomerulonephritis. Relationships
      between BNP and kidney end point [defined as doubling of baseline serum
      creatinine and end-stage kidney disease (ESKD) requiring kidney replacement
      therapy] were measured using Cox models for case-mix and laboratory variables.
      RESULTS: The final analysis covered 485 participants with no loss to follow-up.
      The median follow-up period was 3.2 years. Two hundred and twenty-eight of the
      485 patients reached ESKD requiring dialysis, and baseline serum creatinine
      levels doubled in another 31. The kidney end point was significantly poorer among
      patients with plasma BNP levels above, compared with below a cut-off value of
      86.1 pg/mL indicated from receiver operating characteristic analysis.
      Multivariable Cox regression analysis identified the common logarithm BNP as a
      predictor of kidney end point (adjusted hazard ratio 1.78, 95% CI: 1.28-2.46, P <
      0.01). CONCLUSIONS: Elevation of BNP level is associated with an increased risk
      for accelerated progression of CKD ultimately to ESKD. Monitoring the BNP level
      could be helpful in the management of combined heart and kidney disease.

PMID- 23114907
TI  - A detailed examination of the antibody prevalence and characteristics of anti-ESA
      antibodies.
AB  - BACKGROUND: The antibody characteristics in erythropoiesis-stimulating agent
      (ESA)-treated patients who develop antibody-mediated pure red cell aplasia (PRCA;
      amPRCA) can be described as high-affinity, neutralizing anti-ESA antibodies with
      a mixed immunoglobulin G (IgG) subclass. The characteristics of an early-onset
      anti-ESA antibody response are not well documented, especially in the months
      prior to the development of amPRCA. Therefore, a detailed characterization of
      anti-ESA antibodies was performed in patients in both clinical studies and in a
      post-market setting. Both baseline and post-dose samples were tested and antibody
      positive samples were characterized. Antibody characteristics such as
      concentration, isotype and specificity were evaluated in subjects with non
      neutralizing anti-ESA antibodies and subjects that developed neutralizing anti
      ESA antibodies associated with amPRCA. METHODS: Serum samples were analyzed for
      the presence of anti-ESA antibodies, using a validated surface plasmon resonance
      (SPR)-based immunoassay or SPRIA. RESULTS: Among the clinical studies, pre
      existing non-neutralizing anti-ESA antibodies were found in 6% of the subjects
      from clinical studies in nephrology, oncology and congestive heart failure (CHF).
      After ESA treatment, 2.3% of the subjects developed binding, non-neutralizing
      antibodies with 0.1% confirmed as having an IgG isotype and were specific to the
      ESA protein. IgM antibodies were detected at baseline and post-ESA treatment and
      reported to be specific to the glycosylation of the ESA. No clinical study
      subjects progressed to amPRCA. In contrast, anti-ESA antibody-positive subjects
      from the post-market setting with a confirmed IgG subclass were specific to the
      ESA protein. Subjects that had progressed to amPRCA were noted to have high
      antibody concentrations with neutralizing activity and a diverse IgG subtype.
      CONCLUSIONS: A low prevalence of non-neutralizing anti-ESA IgM specific to
      glycosylation on the ESA and IgG1 antibodies specific to the ESA protein was
      detected across all clinical patient populations. Patients with amPRCA were noted
      to have high IgG antibody concentrations, neutralizing antibodies and the
      presence of anti-ESA IgG4 antibodies.

PMID- 23114908
TI  - Barriers to exercise participation among dialysis patients.

PMID- 23114909
TI  - What is it for?

PMID- 23114910
TI  - [Therapy of hypertension in patients with type 2 diabetes mellitus].

PMID- 23114911
TI  - SNPs identification and its correlation analysis with milk somatic cell score in
      bovine MBL1 gene.
AB  - The objective of this study was to investigate the single nucleotide
      polymorphisms (SNPs) within bovine binding lectin-liver (A) gene (MBL1) and to
      explore its correlation analysis with milk somatic cell score (SCS) which
      reflects mastitis resistance in cattle. Through polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP), created restriction site-PCR
      (CRS-PCR) and DNA sequencing methods, three allelic variant corresponding to the
      G->A mutation at c.1252G>A in intron1, G->A mutation at c.2534G>A and T->C
      mutation at c.2569T>C in exon2 of bovine MBL1 gene, could be detected,
      respectively. The c.2534G>A was a nonsynonymous mutation, resulting in Valine
      (Val) to Isoleucine (Ile) amino acid replacement (p.Val24Ile). The correlation
      analysis between the MBL1 SNPs gene and milk SCS were analyzed and a significant
      correlation with milk SCS was detected in c.2534G>A. The value of milk SCS for
      individuals with genotype GG was significantly lower than those of genotype GA
      and AA. Results showed that genotype GG with the lowest milk SCS was favorable
      for mastitis resistance, whereas genotype AA with the highest milk SCS was easily
      for mastitis susceptibility. Although more investigations are needed to better
      clarify the role of these SNPs on mastitis resistance, MBL1 polymorphism appears
      to be a promising indirect marker to improve dairy mastitis resistance traits in
      cattle.

PMID- 23114912
TI  - Mutations in the D-loop region and increased copy number of mitochondrial DNA in
      human laryngeal squamous cell carcinoma.
AB  - The effects of D-loop mutations and the mtDNA copy number alterations in LSCC are
      poorly understood. Herein, we investigated the features and roles of somatic
      mutations of the D-loop region and copy number alterations in mtDNA of LSCC.
      Using direct sequencing and real-time quantitative PCR, we examined D-loop
      mutations and mtDNA copy number in LSCC tissues, paracancerous normal tissues and
      peripheral vein blood samples from 40 LSCC patients. A student's t test, ANOVA
      test and chi(2) test were used to analyze association among mutations, mtDNA copy
      number alterations with clinicopathologic parameters. The results revealed that
      21 tumors (52.5 %) had somatic mtDNA D-loop mutations with a total of 34
      mutations. Among them, 28 (82.4 %) and 6 (17.6 %) were located in HVII and HVI,
      respectively. D-loop mutations correlated with tumor differentiation and p53
      mutation (P < 0.05), and increased mtDNA copy number. In addition, mtDNA copy
      number in tumor tissues and paracancerous normal tissues were all significantly
      higher than in peripheral blood (P < 0.05). The copy number of mtDNA in the cases
      which carried D-loop mutation was significantly higher than that of the negative
      cases (P < 0.05). These results suggest that the mtDNA D-loop in LSCC is an
      unstable region with a high frequency of somatic mutation and polymorphisms.
      Together with the increase in mtDNA copy number, these factors may play a role in
      carcinogenesis of the larynx.

PMID- 23114913
TI  - Microsatellite loci and the complete mitochondrial DNA sequence characterized
      through next generation sequencing and de novo genome assembly for the critically
      endangered orange-bellied parrot, Neophema chrysogaster.
AB  - A suite of polymorphic microsatellite markers and the complete mitochondrial
      genome sequence was developed by next generation sequencing (NGS) for the
      critically endangered orange-bellied parrot, Neophema chrysogaster. A total of 14
      polymorphic loci were identified and characterized using DNA extractions
      representing 40 individuals from Melaleuca, Tasmania, sampled in 2002. We
      observed moderate genetic variation across most loci (mean number of alleles per
      locus = 2.79; mean expected heterozygosity = 0.53) with no evidence of individual
      loci deviating significantly from Hardy-Weinberg equilibrium. Marker independence
      was confirmed with tests for linkage disequilibrium, and analyses indicated no
      evidence of null alleles across loci. De novo and reference-based genome
      assemblies performed using MIRA were used to assemble the N. chrysogaster
      mitochondrial genome sequence with mean coverage of 116-fold (range 89 to 142
      fold). The mitochondrial genome consists of 18,034 base pairs, and a typical
      metazoan mitochondrial gene content consisting of 13 protein-coding genes, 2
      ribosomal subunit genes, 22 transfer RNAs, and a single large non-coding region
      (control region). The arrangement of mitochondrial genes is also typical of Avian
      taxa. The annotation of the mitochondrial genome and the characterization of 14
      microsatellite markers provide a valuable resource for future genetic monitoring
      of wild and captive N. chrysogaster populations. As found previously, NGS
      provides a rapid, low cost and reliable method for polymorphic nuclear genetic
      marker development and determining complete mitochondrial genome sequences when
      only a fraction of a genome is sequenced.

PMID- 23114914
TI  - Effect of PI3K gene silencing on growth, migration and related proteins
      expression of CD40 signal-mediated gastric cancer cells.
AB  - In this study, we investigate effect of PI3K gene silencing on growth, migration
      and related proteins expression of CD40 signal-mediated gastric cancer cells. We
      observed that combination of sCD40L with PI3K siRNA could significantly inhibit
      AGS cells growth, block cells in G1 phase, and promote tumour cells apoptosis
      after 24 h treatment. Transwell test showed that numbers of cells per visual
      field in group PI3K siRNA or group sCD40L (after 24 h PI3K siRNA or sCD40L alone
      treatment) were fewer than that (32.54 +/- 4.22) in control group. Numbers of
      cells per visual field in (after 24 h combination treatment of PI3K siRNA with
      sCD40L) were significantly fewer than that in group PI3K siRNA or group sCD40L.
      Compared with group sCD40L, expression level of Fas protein in group sCD40L +
      PI3K siRNA was significantly increased. The findings suggest that PI3K siRNA may
      strengthen CD40-induced specific antitumour effect via blocking PI3K/Akt signal
      pathway, resisting tumour immunoediting regulated by CD40 signal. Combination of
      sCD40L and PI3K siRNA is an important mechanism of gastric cancer therapy.

PMID- 23114915
TI  - Complete mitochondrial genome of the Eurasian flying squirrel Pteromys volans
      (Sciuromorpha, Sciuridae) and revision of rodent phylogeny.
AB  - In this study, the complete mitochondrial genome of the Eurasian flying squirrel
      Pteromys volans (Rodentia, Sciuromorpha, Sciuridae) was sequenced and
      characterized in detail. The entire mitochondrial genome of P. volans consisted
      of 16,513 bp and contained 13 protein-coding genes, 22 tRNA genes, two rRNA
      genes, and two non-coding regions. Its gene arrangement pattern was consistent
      with the mammalian ground pattern. The overall base composition and AT contents
      were similar to those of other rodent mitochondrial genomes. The light-strand
      origin generally identified between tRNA ( Asn ) and tRNA ( Cys ) consisted of a
      secondary structure with an 11-bp stem and an 11-bp loop. The large control
      region was constructed of three characteristic domains, ETAS, CD, and CSB without
      any repeat sequences. Each domain contained ETAS1, subsequences A, B, and C, and
      CSB1, respectively. In order to examine phylogenetic contentious issues of the
      monophyly of rodents and phylogenetic relationships among five rodent suborders,
      here, phylogenetic analyses based on nucleotide sequence data of the 35 rodent
      and 3 lagomorph mitochondrial genomes were performed using the Bayesian inference
      and maximum likelihood method. The result strongly supported the rodent monophyly
      with high node confidence values (BP 100 % in ML and BPP 1.00 in BI) and also
      monophylies of four rodent suborders (BP 85-100 % in ML and BPP 1.00 in BI),
      except for Anomalumorpha in which only one species was examined here. Also,
      phylogenetic relationships among the five rodent suborders were suggested and
      discussed in detail.

PMID- 23114916
TI  - Plants as bioindicators for archaeological prospection: a case of study from
      Domitian's Stadium in the Palatine (Rome, Italy).
AB  - In this study, we analyzed the relationship between buried archaeological remains
      (masonries, pavements, and ancient ruins) and spontaneous vegetation growing
      above them. We carried out several vegetation surveys in the Domitian's Stadium
      at the archaeological site of the Palatine (Rome). Vegetation data were collected
      using the Braun-Blanquet approach and elaborated using statistical analyses
      (cluster analysis) to assess the similarity among surveys. Structural,
      chorological, and ecological features of the plant communities were analyzed.
      Results showed that the vegetation responds significantly to the presence of sub
      emerging ancient remains. The plant bioindication of this phenomenon occurs
      through the following floristic-vegetation variations: phenological alterations
      in single individuals (reduction in height, displacement of flowering/fruiting
      period), increase of annual species and decrease of perennial ones, decrease of
      total plant coverage, reduction of maturity level of the vegetation which remains
      blocked at a pioneer evolutive stage. The presence of sub-surfacing ruins
      manifests itself through the dominant occurrence of xerophilous and not
      nitrophilous species (e.g., Hypochaeris achyrophorus L., Aira elegantissima
      Schur, Trifolium scabrum L. ssp. scabrum, Trifolium stellatum L., Plantago
      lagopus L., Medicago minima (L.) L., and Catapodium rigidum (L.) C.E. Hubb. ex
      Dony ssp. rigidum) and in a rarefaction of more mesophilous and nitrophilous
      species (e.g., Plantago lanceolata L., Trifolium pratense L. ssp. pratense,
      Trifolium repens L. ssp. repens, and Poa trivialis L.). Therefore, the vegetation
      can be used as bioindicator for the detection of buried ruins, contributing in
      the archaeological prospection for a general, fast, and inexpensive
      interpretation of the underground.

PMID- 23114917
TI  - Heavy metal enrichment in the soil along the Delhi-Ulan section of the Qinghai
      Tibet railway in China.
AB  - The pollutants that are discharged from roads and traffic have attracted much
      attention recently. Nonetheless, most studies have mainly focused on highways and
      seldom on railways. In this study, soil samples were selected at the embankment
      and perpendicularly at different distances (2, 5, 10, 20, 30, 50, 60, 70, 80,
      100, and 150 m) from the embankment bottom of the Qinghai-Tibet railway.
      Furthermore, soils were selected at four soil depths (5, 10, 20, and 30 cm) of
      each sample at the flat. The enrichment of nine heavy metals (V, Cr, Co, Ni, Cu,
      Zn, Rb, Cd, and Pb) in soils along the Delhi-Ulan section of the Qinghai-Tibet
      railway was studied. The results indicated that the mean concentrations of Cr,
      Ni, Cu, Zn, Pb, and Cd were highest at the embankment. The Cu concentrations in
      soils decreased by an S-curve-shaped function with increasing distance from the
      embankment, while Cd, Pb, and Zn decreased by inverse functions (p < 0.0001). The
      concentrations of other studied metal did not show significant changes with
      increasing distance. After performing a statistical analysis, Pb, Cd, and Zn in
      soils were considered to be influenced by railway operations. However, the
      influence was weak and only spanned less than 5 m from the bottom of the
      embankment horizontally and 10 cm from the surface vertically. The mean
      concentrations of heavy metals in soils along the Delhi-Ulan section of the
      Qinghai-Tibet railway were considered lower compared with those along other
      railways.

PMID- 23114918
TI  - A pilot study on water pollution and characterization of multidrug-resistant
      superbugs from Byramangala tank, Ramanagara district, Karnataka, India.
AB  - Urbanization and industrialization has increased the strength and qualities of
      municipal sewage in Bangalore, India. The disposal of sewage into natural water
      bodies became a serious issue. Byramangala reservoir is one such habitat
      enormously polluted in South India. The water samples were collected from four
      hotspots of Byramangala tank in 3 months. The biochemical oxygen demand (BOD) and
      bacterial counts were determined. The fecal coliforms were identified by
      morphological, physiological, and biochemical studies. The antibiotics
      sensitivity profiling of isolated bacteria were further carried out. We have
      noticed that a high content of BOD in the tank in all the 3 months. The total and
      fecal counts were found to be varied from 1.6 * 10(6) to 8.2 * 10(6) colony
      forming unit/ml and >5,500/100 ml, respectively. The variations in BOD and total
      count were found to be statistically significant at p > 0.05. Many pathogenic
      bacteria were characterized and most of them were found to be multidrug
      resistant. Salmonella showed resistance to cefoperazone, cefotaxime, cefixime,
      moxifloxacin, piperacillin/tazobactam, co-trimoxazole, levofloxacin,
      trimethoprim, and ceftazidime. Escherichia coli showed resistance to
      chloramphenicol, trimethoprim, co-trimoxazole, rifampicin, and nitrofurantoin
      while Enterobacter showed resistant to ampicillin, cefepime, ceftazidime,
      cefoperazone, and cefotaxime. Klebsiella and Shigella exhibited multiple drug
      resistance to conventional antibiotics. Staphylococcus showed resistance to
      vancomycin, methicillin, oxacillin, and tetracycline. Furthermore, Salmonella and
      Klebsiella are on the verge of acquiring resistance to even the strongest
      carbapenems-imipenem and entrapenem. Present study revealed that Byramanagala
      tank has become a cesspool of multidrug-resistant "superbugs" and will be major
      health concern in South Bangalore, India.

PMID- 23114919
TI  - Fluoride pollution of atmospheric precipitation and its relationship with air
      circulation and weather patterns (Wielkopolski National Park, Poland).
AB  - A 2-year study (2010-2011) of fluorides in atmospheric precipitation in the open
      area and in throughfall in Wielkopolski National Park (west-central Poland)
      showed their high concentrations, reaching a maximum value of 2 mg/l under the
      tree crowns. These high values indicate substantial deposition of up to 52
      mg/m(2)/year. In 2011, over 51% of open area precipitation was characterized by
      fluoride concentration higher than 0.10 mg/l, and in throughfall such
      concentrations were found in more than 86% of events. In 2010, a strong
      connection was evident between fluoride and acid-forming ions, and in 2011, a
      correlation between phosphate and nitrite ions was seen. Analysis of available
      data on F(-) concentrations in the air did not show an unequivocal effect on F(-)
      concentrations in precipitation. To find reasons for and source areas of high
      fluoride pollution, the cases of extreme fluoride concentration in rainwater were
      related to atmospheric circulation and weather patterns. Weather conditions on
      days of extreme pollution were determined by movement of weather fronts over
      western Poland, or by small cyclonic centers with meteorological fronts.
      Macroscale air advection over the sampling site originated in the western
      quadrant (NW, W, and SW), particularly in the middle layers of the troposphere
      (2,500-5,000 m a.s.l.). Such directions indicate western Poland and Germany as
      possible sources of the pollution. At the same time in the lower troposphere, air
      inflow was frequently from the north, showing short distance transport from local
      emitters, and from the agglomeration of Poznan.

PMID- 23114920
TI  - Estimation of chlorpyriphos and cypermethrin residues in chilli (Capsicum annuum
      L.) by gas-liquid chromatography.
AB  - Dissipation of chlorpyriphos and cypermethrin in chilli was studied following
      three applications of a combination formulation of Nurelle-D 505 (chlorpyriphos
      50% + cypermethrin 5%) at 1 and 2 L ha(-1) at an interval of 15 days. Residues of
      chlorpyriphos and cypermethrin in chilli were estimated by gas-liquid
      chromatography and confirmed by gas chromatography-mass spectrometry. Half-life
      periods for chlorpyriphos were found to be 4.43 and 2.01 days, whereas for
      cypermethrin these values were observed to be 2.51 and 2.64 days at single and
      double the application rates, respectively. Residues of chlorpyriphos dissipated
      to more than 80% after 10 days at both the dosages. However, residues of
      cypermethrin dissipated to the extent of more than 70% in 7 days. Soil samples
      collected after 15 days of the last application did not show the presence of
      chlorpyriphos and cypermethrin at their respective determination limit of 0.01 mg
      kg(-1). The use of chlorpyriphos and cypermethrin mixture at the recommended
      dosage does not seem to pose any hazards to the consumers, and a waiting period
      of 1 day is suggested to reduce the risk before consumption of green chilli.

PMID- 23114921
TI  - Aurora B expression in metastatic effusions from advanced-stage ovarian serous
      carcinoma is predictive of intrinsic chemotherapy resistance.
AB  - The aim of the present study was to investigate the expression and clinical role
      of the aurora A and aurora B kinases in primary and metastatic serous ovarian
      carcinoma. AURKA and AURKB messenger RNA expression was investigated in 178
      tumors (88 effusions, 38 primary carcinomas, and 52 solid metastases) from 144
      patients with advanced-stage disease using quantitative real-time polymerase
      chain reaction. Aurora A and aurora B protein expression by immunohistochemistry
      was additionally analyzed in 147 tumors. Messenger RNA and protein expression at
      different anatomical sites were studied for association with clinicopathologic
      parameters, including chemotherapy resistance and survival. AURKA and AURKB
      messenger RNA and their protein product were demonstrated in all primary
      carcinomas, solid metastases, and effusions. The expression of AURKA messenger
      RNA and aurora A protein was higher in effusions compared with solid specimens (P
      = .003 and P = .006, respectively). AURKB messenger RNA expression was higher in
      primary carcinomas, and solid metastases obtained prechemotherapy compared with
      postchemotherapy (P < .001 and P = .012, respectively), with no such difference
      in effusions (P > .05). Low aurora B protein expression was associated with
      primary chemotherapy resistance (P = .006) and poor treatment response (P = .013)
      in prechemotherapy effusions. No significant association was found between
      messenger RNA levels or protein expression and progression-free or overall
      survival. The present study documents for the first time frequent aurora A and
      aurora B expression in metastatic ovarian carcinoma, suggesting a role in cancer
      progression, with higher aurora A expression in effusions compared with primary
      carcinomas and solid metastases. Low AURKB messenger RNA expression in
      prechemotherapy effusions might be predictive of intrinsic chemotherapy
      resistance.

PMID- 23114922
TI  - Prognostic value of clinical, morphologic, and immunohistochemical factors in
      patients with bronchiolitis obliterans-organizing pneumonia.
AB  - Bronchiolitis obliterans-organizing pneumonia (BOOP) is an inflammatory and
      fibrosing disease involving the distal bronchioles, bronchiolar ducts, and
      alveoli. We studied 91 patients with BOOP. Univariate analysis was used to relate
      age, sex, smoking, morphology, and expression of immunohistochemical markers
      CD68, D2-40, CD31, CD34, collagen IV, collagen III, platelet-derived growth
      factor receptor, and vascular endothelial growth factor (VEGF) with the response
      to corticosteroid therapy. Seventy-two patients had idiopathic BOOP and 19
      secondary BOOP. The median age of the patients was 59.54 years. Most patients
      were current or former smokers. All cases had a patchy lesion consisting of small
      buds of fibromyxoid tissue in small bronchioles, bronchiolar ducts, and alveoli.
      The buds contained collagen and reticulin fibers, fibroblasts, macrophages,
      mononuclear inflammatory cells, and vessels in different proportions. We found no
      morphologic differences between primary and secondary BOOP. Patients younger than
      38 years and nonsmokers had a significant good response to corticosteroid
      therapy. Favorable morphologic predictors were the presence of large bronchial
      plugs and mild inflammatory reaction (P = .093). By immunohistochemistry, the
      presence of collagen IV with the absence of collagen III, CD68-positive cells and
      positive VEGF were associated with a good response to corticosteroid therapy. We
      conclude that age, smoking, localization, and extension of proliferative
      intrabronchiolar plugs and positive immunostains for CD68, VEGF, and collagen IV
      with negative collagen III were useful to predict response to corticosteroid
      therapy and relapse.

PMID- 23114923
TI  - Elk-1 phosphorylated at threonine-417 is present in diverse cancers and
      correlates with differentiation grade of colonic adenocarcinoma.
AB  - Elk-1 is a member of the Ets family of transcription factors, which are
      identified by a conserved Ets DNA-binding domain that mediates transcriptional
      regulation at Ets sequence--containing promoters. The activation domain of Elk-1
      is important for executing its physiologic functions and contains many
      phosphorylation sites targeted by various MAP kinases following exposure to cell
      stressors or mitogenic stimuli. The different combinations of phosphorylated
      sites allow specificity of cellular responses mediated through redundant
      signaling pathways activated by distinct stimuli. Through phosphorylation of
      S383, mitogen-activated protein kinase (MAPK)-activating stimuli have been shown
      to regulate various processes important in carcinogenesis through transcriptional
      regulation in various cell lines, including proliferation. Phosphorylation at the
      T417 site (pT417), but not the S383 site, is involved in neuronal apoptosis
      induced through dendritic signaling mechanisms and associates with neuronal
      lesions in many Lewy body diseases. This points to distinct roles for these
      different phosphorylation sites in pathophysiologic pathways. However, the S383
      site remains the best characterized in the context of normal function and
      carcinogenesis in cell lines, and less is known about the biochemistry of other
      phosphorylation sites, particularly in more biochemically relevant models. Here,
      we show that Elk-1 pT417 is present in epithelial cell nuclei of various normal
      and cancer tissues and that the number of pT417-positive cells correlates with
      differentiation grade of colonic adenocarcinomas. This nuclear localization and
      correlation with tumor differentiation in adenocarcinoma suggests a potentially
      important transcriptional and biochemical role of this phosphorylation site in
      carcinogenesis of this tumor type.

PMID- 23114924
TI  - Expression of hepatocyte epidermal growth factor receptor, FAS and glypican 3 in
      EpCAM-positive regenerative clusters of hepatocytes, cholangiocytes, and
      progenitor cells in human liver failure.
AB  - Liver regeneration under normal circumstances proceeds through proliferation of
      all cellular elements of the liver. Studies with rodent models have shown that
      when proliferation of hepatocytes is inhibited, progenitor cells arising from the
      biliary compartment transdifferentiate into "oval/progenitor" cells, which
      proceed to differentiate into hepatocytes. Recent studies have shown that the
      same pathways may operate in human liver failure. The growth factor receptors
      (HGF [hepatocyte growth factor] receptor) and epidermal growth factor receptor
      are key mitogenic receptors for both hepatocytes and progenitor cells. Our
      current study used the biliary and progenitor marker EpCAM (epithelial cell
      adhesion molecule) to detect "regenerative clusters" of mixed cholangiocyte
      hepatocyte differentiation. We determined that expression of metabolic equivalent
      and epidermal growth factor receptor occurs in biliary cells, progenitor cells,
      and hepatocytes, whereas activation of metabolic equivalent and epidermal growth
      factor receptor is limited to regenerative cluster hepatocytes. These histologic
      events are associated with expression of apoptosis-inducing FAS and
      mitoinhibitory protein glypican 3. Cell proliferation was overall suppressed in
      regenerative clusters. Transdifferentiation of biliary and progenitor cells
      appears to be regulated by a complex interaction of signals promoting and
      arresting growth.

PMID- 23114925
TI  - Blood plasma separation in a long two-phase plug flowing through disposable
      tubing.
AB  - We report a simple technique to separate plasma from blood in a flowing
      immiscible plug. We investigate the effect of various control parameters such as
      blood dilution, injection flow rate, observation time and fluid properties on
      plasma separation. We find that the technique works best for diluted blood
      samples at low plug velocities and long observation times. We postulate that the
      main mechanism responsible for efficient separation is the sedimentation of blood
      cells in the plug and their subsequent collection by the moving plug causing a
      significant accumulation of cells at the rear of the plug. We discuss the time
      scales determining the sedimentation, advection and collection of a blood cell in
      the immiscible plug and propose a phase diagram that is able to predict the
      operating space for effective plasma separation. We demonstrate that the
      technique allows for the extraction of more than 60% of the plasma by volume from
      1 MUL of diluted blood. We show the practical significance of this method by
      compartmentalizing the separated plasma into discrete microfluidic droplets and
      detecting cholesterol. This technique features low consumption of blood (nL
      scale) and low shear rate (~1 s(-1)). It is inexpensive, easy to use, and has the
      potential to be developed as an efficient point-of-care device for blood
      diagnostics in resource-poor environments. More advanced applications could also
      be envisioned by integrating our plasma separation method into existing
      microfluidic drop manipulation techniques.

PMID- 23114926
TI  - Seizure and developmental outcomes after hemispherectomy in children and
      adolescents with intractable epilepsy.
AB  - PURPOSE: The aim of this study is to describe a series of pediatric
      hemispherectomies, reviewing pathologic substrate, epilepsy characteristics and
      seizure outcome as well as developmental profiles, before and after surgery, in
      different domains. METHODS: Seventeen patients with full pre-surgical work-up,
      minimum follow-up of 12 months, and at least one post-surgical neuropsychological
      evaluation were selected. Three had Rasmussen encephalitis (RE), five hemispheric
      malformations of cortical development (MCD), and nine hemispheric vascular
      lesions. RESULTS: At latest follow-up, all patients with RE and 66.7 % of those
      with vascular lesions are in Engel's class I; in the latter group, pre-surgical
      independent contralateral EEG discharges statistically correlated with a worse
      seizure outcome. Patients with MCD showed the worst seizure outcome. Pre-surgical
      language transfer to the right hemisphere was confirmed in a boy with left RE,
      operated on at 6 years of age. Patients with MCD and vascular lesions already
      showed severe global developmental delay before surgery, which persists
      afterwards. A linear correlation was found between earlier age at surgery and
      better outcome in personal-social, gross motor, and adaptive domains, in the
      vascular lesions group. The case with highest cognitive improvement had
      continuous spike and wave during sleep on pre-surgical EEG. CONCLUSIONS:
      Pathologic substrate was the main factor related with seizure outcome. In
      children with MCD and vascular lesions, although developmental progression is
      apparent, significant post-surgical improvements are restricted by the severity
      of pre-surgical neuropsychological disturbances and a slow maturation. Early
      surgery assessment is recommended to enhance the possibilities for a better
      quality of life in terms of seizure control, as well as better autonomy and
      socialization.

PMID- 23114927
TI  - Use of multiplex real-time PCR for detection of common diarrhea causing protozoan
      parasites in Egypt.
AB  - Diarrhea is an important cause of morbidity and mortality, worldwide. Giardia
      intestinalis, Cryptosporidium spp., and Entamoeba histolytica are the most common
      diarrhea-causing parasitic protozoa. Diagnosis of these parasites is usually
      performed by microscopy. However, microscopy lacks sensitivity and specificity.
      Replacing microscopy with more sensitive and specific nucleic acid based methods
      is hampered by the higher costs, in particular in developing countries.
      Multiplexing the detection of more than one parasite in a single test by real
      time polymerase chain reaction (PCR) has been found to be very effective and
      would decrease the cost of the test. In the present study, stool samples
      collected from 396 Egyptian patients complaining of diarrhea along with 202
      faecal samples from healthy controls were examined microscopically by direct
      smear method and after concentration using formol-ethyl acetate. Frozen portions
      of the same samples were tested by multiplex real-time for simultaneous detection
      of E. histolytica, G. intestinalis, and Cryptosporidium spp. The results indicate
      that among diarrheal patients in Egypt G. intestinalis is the most common
      protozoan parasite, with prevalence rates of 30.5 and 37.1 %, depending on the
      method used (microscopy vs. multiplex real-time PCR). Cryptosporidium spp. was
      detected in 1 % of the diarrheal patients by microscopy and in 3 % by real-time
      PCR. While E. histolytica/dispar was detected in 10.8 % by microscopy, less than
      one fifth of them (2 %) were found true positive for Entamoeba dispar by real
      time PCR. E. histolytica DNA was not detected in any of the diarrheal patients.
      In comparison with multiplex real-time PCR, microscopy exhibited many false
      positive and negative cases with the three parasites giving sensitivities and
      specificities of 100 and 91 % for E. histolytica/dispar, 57.8 and 85.5 % for G.
      intestinalis, and 33.3 and 100 % for Cryptosporidium spp.

PMID- 23114928
TI  - Epoxy-based monoliths for capillary liquid chromatography of small and large
      molecules.
AB  - A versatile epoxy-based monolith was synthesised by polycondensation
      polymerisation of glycidyl ether 100 with ethylenediamine using a porogenic
      system consisting of polyethylene glycol, M(w) = 1000, and 1-decanol.
      Polymerisation was performed at 80  degrees C for 22 h. A simple acid hydrolysis
      of residual epoxides resulted in a mixed diol-amino chemistry. The modified
      column was used successfully for hydrophilic interaction liquid chromatography
      (HILIC) of small molecule probes such as nucleic acid bases and nucleosides,
      benzoic acid derivatives, as well as for peptides released from a tryptic digest
      of cytochrome c. The mixed-mode chemistry allowed both hydrophilic partitioning
      and ion-exchange (IEX) interactions to contribute to the separation, providing
      flexibility in selectivity control. Residual epoxide groups were also exploited
      for incorporating a mixed IEX chemistry. Alternatively, the surface chemistry of
      the monolith pore surface rendered hydrophobic via grafting of a co-polymerised
      hydrophobic hydrogel. The inherent hydrophilicity of the monolith scaffold also
      enabled high performance separation of proteins under IEX and hydrophobic
      interaction modes and in the absence of non-specific interactions.

PMID- 23114929
TI  - A concept study on non-targeted screening for chemical contaminants in food using
      liquid chromatography-mass spectrometry in combination with a metabolomics
      approach.
AB  - A generic method to screen for new or unexpected contaminants at ppm levels in
      food has been developed. The method comprises an acidic acetonitrile extraction,
      detection with ultra-high-pressure liquid chromatography coupled to electrospray
      ionisation time-of-flight mass spectrometry and statistical evaluation using a
      metabolomics approach comparing suspected contaminated food with uncontaminated
      foods. The method was tested for 26 model contaminants from 100 MUg/g down to 0.4
      MUg/g in three brands of fresh orange juice. Blinded statistical evaluation
      revealed signals from all added contaminants detectable by liquid chromatography
      electrospray ionisation using positive ionisation mode, while only two false
      positive signals were reported. The method is primarily intended to be used for
      investigation of food samples suspected to be contaminated with unknown
      substances. Additionally it could be used to continuously monitor for appearance
      of new food contaminants as a complement to the specific targeted analysis that
      is today's foundation of food safety analysis.

PMID- 23114930
TI  - Nutritional intervention in oncohematological patient.
AB  - BACKGROUND: Oncohematological diseases such as lymphoma or leukaemia affect an
      increasing number of newly diagnosed patients in Spain and other countries. Both
      disease and treatment may have a negatively impact in the nutritional status of
      the patient. Malnutrition is not uncommon among oncohematological patients. This
      situation can compromised the course of the disease, the clinical response of the
      treatment and the patient's quality of life. METHOD: The implementation of a
      multidisciplinary approach and a systematic and protocolled nutritional
      assessment would be useful when dealing with haematological malignancies.
      RESULTS: We present a proposal of protocol for nutritional intervention in
      oncohematological patients. This proposal is been developed from the analysis of
      the published literature as well as clinical practice of a multi-disciplinary
      team specialized in the management of patients with haematological malignancies.

PMID- 23114931
TI  - Immunoenhanced enteral nutrition formulas in head and neck cancer surgery: a
      systematic review.
AB  - INTRODUCTION: Significant malnutrition exists in a high percentage of patients
      with head and neck cancer. Malnutrition is associated with defects in immune
      function that may impair the host response to malignancy. Malnutrition and
      immunosupression make patients highly susceptible to postoperative infections and
      complications. OBJECTIVES: Some studies of patients receiving immuno-nutrition in
      the perioperative period in head and neck cancer have shown beneficial effects on
      clinical outcome and inmune status. The authors carried out a systematic review
      of randomised control trials to determine whether perioperative immunonutrition
      has a role in the treatment of head and neck cancer. METHODS: 14 trials of
      polymeric nutritional supplementation with immunonutrition were identified. Two
      studies compared two types of immunonutrition. RESULTS: A reduction in the length
      of postoperative hospital stay was seen in some trials, but the reason for this
      reduction is not clear. Some studides showed statistical differences with less
      complications in arginine-enhanced group and also showed a significant decrease
      of fistula complications in patients treated with a high arginine dose enhanced
      formula, if compared with a medium dose of arginine. CONCLUSION: [corrected]
      Those planning future studies face challenges. A suitable powered clinical trial
      is required before firm recommendations can be made on the use of immunonutrition
      in head and neck cancer patients postoperatively.

PMID- 23114932
TI  - [We and zinc].
AB  - Nutrition is the basis of human physiological processes. Inadequate nutrition can
      lead to dysfunction in the metabolic chain links. One of the most important
      micronutrients is zinc, as evidenced by its wide range of carriers in the body.
      Zinc intake has a large margin in the current world population, may be 7 mg/d in
      the UK, reaching 15 mg/d in the U.S., although of course, the RDA's are set
      according to age, sex , physiological status (pregnancy, lactation, etc..), or
      disease. It is known that zinc is essential for the structure and function as
      well as DNA and enzymes, coenzymes, hormones and so on. Life is short, zinc,
      since the most rapidly absorbed and is transferred to tanks where it is stored,
      so the amount available zinc in the blood cannot be the amount "real". In this
      work we have done a mini-review of the passage of zinc by the body trying since
      their intake to their tour of the blood in both healthy and sick people.

PMID- 23114933
TI  - [Comparison of two nutritional screening tools for predicting the development of
      complications in hospitalized patients].
AB  - BACKGROUND: The prevalence of malnutrition in hospitalized patients is high and
      has been associated with higher morbimortality. Currently no nutritional
      screening tool is considered the gold standard for identifying nutritional risk.
      The aims of this study were to evaluate the prevalence of nutritional risk in
      hospitalized patients using the nutritional screening tools Mini Nutritional
      Assessment (MNA) and Nutrition Risk Screenig 2002 (NRS 2002) and to identify the
      ability for predicting development of complications. METHODS: We evaluated 57
      patients admitted within the first 48 h in different medical or surgical wards of
      the hospital. The patients were assessed by MNA and NRS 2002 and using
      anthropometric and laboratory parameters. Agreement between MNA and NRS 2002 was
      analyzed with the kappa index. ROC curves were used for assessing the validity of
      the both tools in predicting complications with determination of the area under
      the curve (AUC). RESULTS: The prevalence of patients at nutritional risk was
      38.6% with the NRS-2002 and 49.1% with the MNA. The agreement between two tools
      was moderate (kappa = 0.436, p = 0.001). The incidence of complications was
      significantly higher in patients at nutritional risk defined by the NRS 0,002)
      but not according to the MNA (28.6% vs. = 2002 (40.9% vs. 5.7%; p 0.08).
      Sensitivity for predicting complications was 81.8% with = 10.3%, p the NRS 2002
      and 72.7% with the MNA and specificity was 71.7% and 56.5% respectively. By ROC
      curve, both tests were valid to identify the risk of complications: NRS 2002 AUC
      = 0.768 (confidence interval (IC) 95%: 0.637-0.869) and MNA AUC = 0.646 (IC 95%:
      0.508-0.768), but the AUC was significantly higher with the NRS 2002 (p = 0.047).
      CONCLUSIONS: The prevalence of nutritional risk in hospitalized patients is high.
      NRS 2002 is a screening tool more valid than MNA to predict the development of
      complications.

PMID- 23114934
TI  - Nutritional status, systemic inflammation and prognosis of patients with
      gastrointestinal cancer.
AB  - INTRODUCTION: Systemic inflammatory response in individuals with cancer is
      related to a progressive reduction in total body mass, especially lean mass.
      OBJECTIVE: The aim of the present study was to determine the association between
      nutritional status and systemic inflammatory response in patients with
      gastrointestinal cancer. METHODOLOGY: A case series study was carried out
      involving 30 male and female adults and elderly patients with no prior treatment
      sent consecutively for surgery. Nutritional status was assessed using subjective
      and objective methods. Inflammatory response and prognosis were assessed through
      the determination of C-reactive protein (CRP), the Glasgow Prognostic Score and
      CRP/albumin ratio. RESULTS: High prevalence values were found for systemic
      inflammation (73%), a greater risk of infectious and/or inflammatory complication
      (43%) and worse prognosis (50%). The percentage of weight loss was correlated
      with serum CRP (r = 0.38; p < 0.05) and the CRP/albumin ratio (r = 0.44; p <
      0.05). Inflammation markers and prognosis were negatively correlated with serum
      albumin (r = -0.50; p < 0.05), body mass index (r = -0.39; p < 0.05) and total
      lymphocyte count (r = -0.37; p < 0.05). Patients with weight loss and
      malnourishment had significantly higher serum CRP and CRP/albumin ratio values as
      well as lower serum albumin levels in comparison to those without weight loss and
      in well-nourished. CONCLUSION: Nutritional status is related to inflammation
      markers and prognosis in patients with gastrointestinal cancer. The diagnosis and
      attenuation of systemic inflammation should be part of the nutritional care of
      these patients.

PMID- 23114935
TI  - [Food sources and average intake of calcium in a representative sample of Spanish
      schoolchildren].
AB  - INTRODUCTION: There is controversy about the adequacy of calcium intake to that
      recommended in Spanish schoolchildren. Some studies indicate that the intake is
      inadequate in a variable percentage of children, while others insist on the
      danger of an excessive intake in a huge percentage of this population. AIM: To
      assess calcium intake and food sources of this nutrient in a representative
      sample of Spanish children and to judge the adequacy of its contribution to the
      coverage of recommended intakes. METHODS: 903 schoolchildren (7 to 11 years) from
      10 Spanish provinces (Tarragona, Caceres, Burgos, Guadalajara, Valencia,
      Salamanca, Cordoba, Vizcaya, Lugo and Madrid) were studied. They constituted a
      representative sample of the Spanish schoolchildren population. The energy and
      nutrient intake was determined using a "Food record questionnaire" for 3 days,
      including a Sunday. Calcium intake was compared with the recommended intakes (RI)
      for the mineral. Weight and height were recorded and body mass index (BMI)
      calculated. RESULTS: In the studied group (55.3% girls and 44.7% of children),
      30.7% had an excess body weight (23.3% overweight and 7.4% obesity). Calcium
      intake was 859.9 +/- 249.2 mg / day (79.5% of the recommendations). 76.7% of
      children had intakes below 100% of those recommended and 40.1% below of 67% of
      RI. The ratios calcium/phosphorus (0.74 +/- 0.21) and calcium/protein (10.1 +/-
      2.8) and the index of nutritional quality for calcium (0.78 +/- 0.29) were lower
      than recommended in 91.6%, 99.8% and 81.1% of children, respectively. Dietary
      calcium came from dairy products (64.7%), dietetic products and infant formulae
      (7.6%), cereals (7.3%), vegetables (3.5%), fruits (3.4%), pre-cooked meals
      (3.3%), meats (2.8%), fishes (2.8%) and pulses (2.2%), with no differences by
      gender. CONCLUSION: Calcium intake was lower than recommended in 76.7% of the
      children and 40.1% had insufficient intake (< 67% of RI). Having in mind that the
      main calcium source was dairy products (64.7%), increase consumption of this food
      group is recommended, especially in the 37.1% of children who did not reach the 2
      recommended servings per day.

PMID- 23114936
TI  - Gender-specific influence of health behaviors on academic performance in Spanish
      adolescents: the AFINOS study.
AB  - INTRODUCTION: New paradigms based on the multifactorial etiology of chronic
      diseases and behavioral outcomes suggest that a combination of health behaviors
      may have more impact on the outcome of interest than any single factor.
      OBJECTIVE: To examine the independent and combined influence of four health
      behaviors on school performance in Spanish adolescents. METHODS: A total of 1825
      Spanish adolescents reported their grades in Language and Literature (LL) and
      Math. Body mass index, family structure and school-related factors (attitude to
      school, need to repeat > 1-yr and absenteeism) were self-reported. Adolescents
      were dichotomized as healthy or unhealthy based on meeting or not meeting
      lifestyle recommendations on physical activity, TV viewing, sleep and fruit
      intake. Each adolescent was also scored according to the number of healthy
      recommendations fulfilled. RESULTS: In boys, there were no associations between
      health behaviors and academic performance. Good academic performance in girls was
      associated with physical activity (P < 0.05) or fruit consumption (P < 0.05).
      Moreover, girls who scored 3-4 health behaviors showed higher odds of passing LL
      (OR = 3.18, P < 0.001), Math (OR = 1.75, P = 0.028) or LL+Math (OR = 2.32, P =
      0.001) compared with those with 0-1 health behaviors. All the analyses were
      adjusted by weight status, family context and different school-related factors.
      CONCLUSIONS: A combination of health behaviors may have a positive influence on
      academic performance in adolescent girls.

PMID- 23114937
TI  - Five year trends on total and abdominal adiposity in Spanish adolescents.
AB  - OBJECTIVE: To assess five years trends in total and abdominal fat in Spanish
      adolescents. DESIGN: Two cross-sectional studies: adolescents from the city of
      Zaragoza (Spain) assessed during 2001-2002 and 2006-2007. SUBJECTS: 399
      adolescents in 2001-02 and 392 adolescents in 2006-07. MAIN OUTCOME MEASUREMENTS:
      Socio-economic status was assessed using the education level of both parents. A
      complete anthropometric assessment was performed in both surveys using the same
      methodology: weight, height, skinfold thickness (biceps, triceps, subscapular,
      suprailiac, thigh and calf) and circumferences (waist and hip). The body mass
      index (BMI) and the sum of 6 skinfold thicknesses were calculated. Body fat
      percentage (BF%) was also calculated by the formulas described by Slaughter et
      al. RESULTS: After adjusting for age and pubertal status, only females showed a
      significantly decrease in weight, BMI and waist circumference, and a significant
      increase in the sum of 6 skinfolds (all P < 0.05 and Cohen's d >= 0.25) in 2006
      2007, when compared to values obtained in 2001-2002. Males did not show any
      significant change between the two surveys. Concerning centile values, a slight
      general reduction was observed in weight, BMI and waist circumference for both
      males and females. On the contrary, the sum of 6 skinfolds and the BF% were
      higher in 2006-2007 than in 2001-2002. CONCLUSION: According to these results,
      there might be a levelling-off in the trends of BMI, BF% and waist circumference
      in male adolescents from Zaragoza. In females, despite a trend towards higher
      body fat mass, there was a trend towards lower BMI and waist circumference
      values.

PMID- 23114938
TI  - [Comparison between the quality of life and nutritional status of nutrition
      students and those of other university careers at the Santo Thomas University in
      Chile].
AB  - OBJECTIVE: To determine and compare the quality of life, nutritional status, and
      self-perceived body image between nutrition students and students from other
      careers from the University Santo Tomas-Vina del Mar. METHODS: We evaluated 200
      student volunteers (100 nutrition students and 100 students from other careers)
      with a quality of life survey, a nutritional evaluation, and a survey of body
      image perception. RESULTS: The group of nutritional students perceived a lower
      quality of life, consumed less tobacco, and was less sedentary. Women of the
      nutritional group had a lower BMI and showed a lower hip circumference. Men of
      the nutritional group also showed a lower hip circumference. The nutritional
      group consumed more milk, chicken, and fish in their diet. Both groups presented
      an elevated consumption of alcohol. The concordance between BMI and body image
      was low, 34% in the nutritional group and 38% in the other careers group (Kappa
      0.04 and 0.02). CONCLUSION: With respect to perception of quality of life,
      students from other careers perceived a better quality of life, however students
      from the nutritional group presented better nutritional status and selection of
      food.

PMID- 23114939
TI  - [Effect of an 8-week aerobic training program during physical education lessons
      on aerobic fitness in adolescents].
AB  - OBJECTIVE: To determine the effect of a high intensity aerobic training program
      of 8 weeks, developed during physical education classes, on the aerobic capacity
      of adolescents aged 15 to 18 years. METHODS: A total of 84 adolescents (51 boys
      and 33 girls) participated in this study. The aerobic capacity (VO(2)max) was
      measured directly with a portable gas analyzer (K4b2, Cosmed) during the
      performance of the 20 Meters Shuttle Run Test (20mSRT). The sample was divided
      into 2 experimental groups (G2S and G3S) and 1 control group. The training
      program was composed of aerobic physical activity (75-80% VO(2)max.). The G2S
      developed 2 sessions per week while the G3S made 3. RESULTS: The G2S increased
      VO(2)max (boys: from 55.7 to 56.6 ml/kg/min; girls: from 37.8 to 38.7 ml/kg/min;
      p < 0.001) and the number of stages in the 20mSRT (9.0% boys, p < 0.001; 20.0%
      girls, p < 0.001). The G3S also increased VO(2)max (boys: from 54.9 to 56.0
      ml/kg/min; girls: from 36.0 to 38.7 ml/kg/min) and the number stages in the
      20mSRT (10.4% boys, p < 0.001; 32.3% girls, p < 0.001). In G2S and G3s, girls
      showed greater improvement than boys. CONCLUSIONS: A high intensity aerobic
      training program developed during 8 weeks, 2 sessions per week, improves aerobic
      capacity of the students. An extra session of intense exercise for week is a
      greater improvement in girls, but do not produce such effects in boys.

PMID- 23114940
TI  - A six month randomized school intervention and an 18-month follow-up intervention
      to prevent childhood obesity in Mexican elementary schools.
AB  - BACKGROUND: The objective of this study, focused on parents and children to
      reduce sedentary behavior, consumption of soft drinks and high-fat and salt
      containing snacks, and increase the consumption of fruits and vegetables, was to
      assess the effect of a six month intervention and an 18 month follow-up
      intervention on the body mass index, food consumption and physical activity of
      2nd and 3rd grade elementary school children. METHODS: This was a randomized
      cluster controlled trial. School children were selected from 2nd and 3rd (n =
      532) grade. MEASUREMENTS: BMI z-score for age and sex was calculated and
      classified according to the WHO (2006). Abdominal obesity was defined as WC >
      90th of NHANES III. RESULTS: At six months of the study differences were observed
      in BMI, -0.82 (p = 0.0001). At 24 months, results such as an increase of z-score
      BMI and waist circumference, a decrease in abdominal obesity, eighth per cent
      remission and an incidence of 18% of overweight and obesity were observed.
      Additionally, an increase (p = 0.007) in vegetable intake and physical activity
      (p = 0.0001) was also reported, along with a decrease in sedentary activities and
      the consumption of snacks high in fat and salt. CONCLUSIONS: The results of this
      study indicate that with a comprehensive intervention there is a positive
      response to lifestyle changes and a reduction of abdominal obesity.

PMID- 23114941
TI  - [Training model for integral treatment of patients with eating disorders
      resistant to change].
AB  - The need to find effective treatments for patients with Anorexia or Bulimia
      nervosa has led to the professionals who care for them to develop new forms of
      treatment that take into account the variables that cause resistance to change.
      Patients in this study (2006-2009) have the following characteristics: 340
      patients who have 7 or more years of evolution and/or have tried numerous
      previous treatments without having succeeded in starting and / or maintaining the
      desired changes, that allowed them to recover steadily. As the proposed
      treatment, the patient-treatment team is based on the principles of the training
      model. It considers the patient holistically, it informs and provides him with
      resources to increase its commitment to change. Teaches the patient to take care
      physically and mentally as a way to regain their health and leave the disorder in
      a stable way. Includes family members as essential support in the recovery of
      their closest. Therapists require extensive experience in the treatment of ED,
      flexibility, ability to integrate with other team members even if they use
      different theoretical models, skills for group sessions, ability to handle
      negative emotions and frustration tolerance. Finally, the model presented below
      has been implemented, recovered patients whose stay in the disorder exceeded 15
      years of development and led to permanent occupational disability.

PMID- 23114942
TI  - Nutritional assessment of hospitalized HIV-infected patients by the phase angle z
      score measurement.
AB  - BACKGROUND: This study analyzed the phase-angle (PA) values of hospitalized HVI
      infected patients by comparing them with those reported for a healthy population
      and investigated their relation with nutritional parameters. METHODS: This is a
      cross-sectional study including 101 hospitalized patients diagnosed with HIV
      infection and evaluated by bioimpedance, anthropometry and biochemical tests. The
      phase angle values, weight loss percentage (%WL), body mass index (BMI), arm
      muscle circumference (AMC), tricipital skinfold (TSF), body fat percentage (%BF)
      and albumin were considered. In order to compare with values for the healthy
      population, the PA z-score of the patients under study was calculated. Spearman's
      correlation and the multiple linear regression model were used to identify
      nutritional parameters associated with the PA z-score. RESULTS: The patients
      showed a mean PA z-score of -2.6 +/- 1.5, and only 6.6% of them with a positive
      value. The PA z-score values correlated with %WL (r = -0.51; p < 0.0001), albumin
      (r = 0.49; p < 0.0001), BMI (r = 0.58; p < 0.0001), AMC (r = 0.41; p < 0.0001),
      TSF (r = 0.47; p < 0.001) and %BF (r = 0.48, p < 0.0001). In multiple analysis
      %WL (p = 0.008), albumin (p = 0.01), AMC (p < 0.0001) and %BF (p = 0.0003)
      remained associated with the score. CONCLUSIONS: Low PA z-score values were
      observed, suggesting a worse clinical prognosis for the patients. The inclusion
      of the PA z-score as a nutritional indicator during care provision to HIV
      infected patients is recommended.

PMID- 23114943
TI  - [Central venous catheters-related infections in patients with parenteral
      nutrition].
AB  - INTRODUCTION: Infections related to central venous catheters (CVC) are
      complications with a high prevalence and possible serious consequences.
      Administration of total parenteral nutrition (TPN) is a risk factor, although the
      information available for these patients and conventional inpatient units is
      scarce. OBJECTIVE: To determine the rate of catheter-related bacteremia (CRB) in
      patients with TPN and to identify possible relationships with administration
      route or place of insertion, to determinate the current situation and identify
      possible preventive measures. METHOD: Prospective-observational study of 13
      months. All adult patients who received TPN were included. Infection rate used
      was the CRB per 1,000 days of CVC. RESULTS: 176 CVC were registered in 159
      patients. In 47% of CVC, vein access was jugular vein, despite being a location
      of greatest risk of infection. In critically ill patients, which followed a zero
      bacteremia project, there was no cases of infection. In other patients,
      bacteremia rate was 13.10 per 1,000 days of CVC. The average time elapsed between
      catheter insertion and infection was 11 days (range: 4-22) and the most frequent
      species were S. epidermidis (38%) and S. hominis (19%). DISCUSSION: In our
      environment there is a high rate of BRC in non-critical patients, with a high
      proportion of CVC in locations with higher risk of infection, despite not having
      found in the sample a higher rate of infection depending on the access route.
      Place of insertion, operating room face ward, is related to a lower rate of BRC.
      Measures to standardize clinical practice may reduce its incidence. The zero
      bacteremia project is confirmed as a highly effective method.

PMID- 23114944
TI  - Increasing leptin level in abstaining alcohol-dependent women.
AB  - INTRODUCTION: Leptin, hormone secreted by the fat tissue, changes the signaling
      of dopamine in the nucleus accumbens, which directly affects the sensitivity of
      reward and modulation of abstinence. AIMS: To evaluate the level of serum leptin
      and its relation to nutritional status among alcoholic abstainers and non
      abstinent. METHODS: Patients of both sexes, over 18 years old and who used
      alcohol as their primary drug were included in the study. Abstaining patients
      were separated according to the time without the use of the drug as A2 (1-3 month
      abstainers) and A3 (4 month and over-abstainers). Waist circumference (WC), body
      fat percentage (%BF) and weight and height were measured to calculate Body Mass
      Index (BMI). Blood samples were collected for leptin measurement. RESULTS: Mean
      levels of leptin, leptin/BMI, leptin/%BF were higher in all women categories.
      Abstaining women (A2) also showed higher leptin, leptin/BMI and leptin/ %BF than
      non-abstinent (p = 0.039; p = 0.023; p = 0.023). Statistical differences were
      also shown among abstaining women A2 and A3 as well a significant positive
      association between leptin levels and BMI and leptin and WC in active female
      drinkers (leptin * BMI: r = 0.91; p < 0.01; leptin * WC: r = 0.87; p = 0.001).
      However, a significant association was not shown among these results in
      abstaining women (leptin * BMI: r = 0.28; p = 0.37/ leptin * WC: r = -0.32, p =
      0.92). CONCLUSION: Our results suggest that leptin levels seem to increase only
      in abstaining women. This result can be related to the length of abstinence.

PMID- 23114945
TI  - Evidence-based nutritional recommendations for the prevention and treatment of
      overweight and obesity in adults (FESNAD-SEEDO consensus document). Methodology
      and executive summary (I/III).
AB  - The present study is a consensus document of two Spanish scientific associations,
      FESNAD (Spanish Federation of Societies of Nutrition, Food and Dietetics
      Associations) and SEEDO (Spanish Association for the Study of Obesity), about the
      role of the diet in the prevention and treatment of overweight and obesity in
      adults. In this part of the document the methodology and the classification of
      levels of evidence are described. In order to reach the strongest evidence
      possible, a systematic review of 543 medical studies dealing with these issues
      published in the last 15 years (from January 1st 1996 to January 31st 2011) has
      been conducted. In the executive summary, along with the obtained evidences, a
      set of degree-classified recommendations are established. These recommendations
      could constitute a useful tool to design food guides addressed to the nutritional
      counseling for obesity and overweight treatment.

PMID- 23114946
TI  - Evidence-based nutritional recommendations for the prevention and treatment of
      overweight and obesity in adults (FESNAD-SEEDO consensus document). The role of
      diet in obesity prevention (II/III).
AB  - This study is a consensus document of two Spanish scientific associations, FESNAD
      (Spanish Federation of Nutrition, Food and Dietetetic Associations) and SEEDO
      (Spanish Association for the Study of Obesity), about the role of the diet in the
      prevention and of overweight and obesity in adults. It is the result of a careful
      and systematic review of the data published in the medical literature from
      January 1st 1996 to January 31st 2011 concerning the role of the diet on obesity
      prevention. The conclusions obtained have been classified according several
      evidence levels. Subsequently, in agreement with these evidence levels, different
      degree recommendations are established. These recommendations could be
      potentially useful to design food guides as part of strategies to prevent
      overweight and obesity.

PMID- 23114947
TI  - Evidence-based nutritional recommendations for the prevention and treatment of
      overweight and obesity in adults (FESNAD-SEEDO consensus document). The role of
      diet in obesity treatment (III/III).
AB  - This study is a consensus document of two Spanish scientific associations, FESNAD
      (Spanish Federation of Nutrition, Food and Dietetic Associations) and SEEDO
      (Spanish Association for the Study of Obesity), about the role of the diet in the
      treatment of overweight and obesity in adults. It is the result of a careful and
      systematic review of the data published in the medical literature from January
      1st 1996 to January 31st 2011 concerning the role of the diet on obesity
      treatment. The achieved conclusions have been classified into various evidence
      levels. Subsequently in agreement with these evidence levels, different degree
      recommendations are established being potentially useful to design food guides as
      part of strategies addressed to the treatment overweight and obesity.

PMID- 23114948
TI  - [Increased risk of obesity and central obesity in sedentary postmenopausal
      women].
AB  - AIMS: To establish the influence of a sedentary behavior (sit time) on body
      composition in elderly women from Aragon. METHODS: A total of 457 women
      participated in the study. Hours of walking were used to define the active
      behavior (> 1 vs. < 1 h/day) and hours of sitting were used to establish the
      sedentary behavior (> 4 vs. < 4 h/day). Anthropometric evaluation was conducted
      following the ISAK recommendations. Fat mass was estimated through electrical bio
      impedance. Differences between groups were analyzed by ANOVA and logistic
      regression analysis was used to study the association between active and
      sedentary behaviors with body composition. RESULTS: The sedentary group had
      higher weight, BMI, waist circumference and fat mass than the non-sedentary group
      (all p < 0.05). In addition, those women who sat more than 4 h/day had 1.7, 2.7
      and 1.7-fold higher odds ratio for having overweight, obesity and central
      obesity, respectively, regardless of the hours of walking (95% IC [1.006-2.739];
      [1.518-4.491] y [1.154-2.565]). When activity and sedentary levels were studied
      together, active and sedentary women were 2.0 times more likely to be overweight
      (95% CI [0.995-3.961]), 4.4 to be obese (95% CI [2.101-9.264]) and 2.3 for having
      central obesity (95% CI [1.329-3.939]) than women with an active and non
      sedentary behavior. CONCLUSION: Being sitting more than 4 hours a day increases
      the risk of overweight, obesity and central obesity, regardless of the hours of
      walking in postmenopausal women.

PMID- 23114949
TI  - [Impact of the creation of a nutritional support team on the quality, safety and
      effectiveness of total parenteral nutrition].
AB  - INTRODUCTION: Parenteral nutrition (PN) is an essential component in the
      treatment of many hospitalized patients; however its use is associated to severe
      complications. The monitoring of these patients has been demonstrated as an
      effective method for the success of nutrition therapy; therefore, nutritional
      support teams play an important role to increase the effectiveness and efficiency
      of the PN. In Spain, there is no data available about the situation of
      nutritional support teams in hospitals. OBJECTIVE: Develop a nutritional support
      team in our hospital and analyze the interventions and outcomes in terms of
      quality, effectiveness and safety. METHODS: Retrospective, cross-sectional study.
      Patients with PN were selected during two months, corresponding to the period
      before and after the creation of the nutritional support team (group 1 and 2,
      respectively). The functions of the nutritional team include: nutritional
      evaluation, daily monitoring of vital signs and glycemia, detailed analytical
      control, management of PN complications, between others. RESULTS: 67% of patients
      in group 1 (n = 24) maintain the PN < 7 days, versus 22% in group 2 (n = 38). In
      group 1, no patient had a nutritional assessment, neither daily vital signs
      monitoring (100% in group 2). Detailed analytical control was carried out in the
      4% of group 1 and 79% of group 2. In group 2, albumin and prealbumin levels
      remain stable or increased in the 66% and 88% of patients, respectively. No
      patient reached triglyceride > 400 mg/dl. 34% of patients showed glycemia > 140
      mg/dl (100% of them were solved), and 26% of patients underwent hepatic
      dysfunction (50% were solved). No refeeding syndrome was reported (thiamine was
      added to PN in 34% of patients). DISCUSSION: the nutritional support team work
      has notably increased the quality, safety and effectiveness of PN. This study
      demonstrates the need to incorporate multidisciplinary nutritional teams in
      hospitals and the benefit obtained in the patient medical care.

PMID- 23114950
TI  - [Evaluation of drug administration through enteral feeding tubes in hospitalized
      patients].
AB  - OBJECTIVE: To describe the administration of drugs through nasogastric tubes by
      the nursing staff of a tertiary hospital and to identify the most common
      administration errors. METHODS: An observational study was carried out between
      November of 2010 and March of 2011. The study population was the nursing staff of
      the hospital. A questionnaire was created asking about the daily practice of
      drugs administration through the nasogastric tube; a score was assigned to each
      question. A document on correct administration techniques of drugs through the
      nasogastric tube was elaborated, which served for the comparison of the answers
      obtained. RESULTS: A total of 162 surveys were answered. Most of the staff
      (44.5%) had a deficient knowledge on the proper administration techniques. 69.7%
      of the staff stated to have grinded some time a tablet with enteric coverage, and
      66.2% a tablet with modified release. A significant lower number of perceived
      obstructions per month was obtained in those nurses with higher degree of
      knowledge, in those consulting the Pharmacy Department when they had doubts, and
      in those never having grinded a tablet with enteric coverage of modified release.
      CONCLUSIONS: It is observed that the knowledge on proper administration of drugs
      through the nasogastric tube by the nursing staff is deficient; therefore, it
      would be convenient to carry out specific training courses as well as a closer
      collaboration between the Pharmacy department and the Nursing units.

PMID- 23114951
TI  - [Incidence of catheter-related infection and associated risk factors in
      hospitalized patients with parenteral nutrition].
AB  - INTRODUCTION: The most severe complication of parenteral nutrition (PTN) is
      catheter-related infection (CRI). OBJECTIVES: To study the incidence rate and
      factors associated to CRI. MATERIAL AND METHODS: 271 patients followed at the
      Nutrition Unit for 6 months. The composition of the PTN was calculated according
      to the metabolic demands. 20.3% received a lipid solution enriched with omega-3
      fatty acids (SMOF Fresenius Kabi(r)) and 79.7% with olive oil (Clinoleic
      Baxter(r)). RESULTS: The rate of CRI was 25 per 1,000 days of PTN (55 patients:
      61.7+/-17.8 years, 60.3% males, 29.3+/-10.6 days of hospital stay and 10.4%
      mortality). Coagulase-negative Staphylococcus was the most frequently isolated
      microorganism. There were no differences by age, gender, mortality, or
      composition of the PTN between patients with or without infection. The patients
      treated with omega-3 received more calories with the PTN, at the expense of
      higher intake of glucose and lipids. However, the rate of infection was similar,
      although there was a not significant trend towards a lower infection rate when
      using the omega-3 composition (14.5% vs. 23.1%, respectively, p = 0.112). The
      duration of the nutritional support was higher in patients with CRI (13.0 +/- 9.7
      vs. 9.3 +/- 8.1, p = 0.038). Total mortality (16.9%) was independent of the
      presence or absence of CRI (10.4% vs. 18.7%, p = 0.090) or of the use of omega-3
      lipids or olive oil in the PTN (10.9% vs. 18.5%, p = 0.125). CONCLUSION: Patients
      submitted to PTN have a high rate of CRI. The presence of infection is related to
      the duration of the PTN, being independent of the age, gender, and composition of
      the solution. The use of omega-3 lipid solutions may be beneficial although
      further studies are needed to confirm this.

PMID- 23114952
TI  - [Quality control an assessment system. Its location within a program for food,
      nutrition and metabolic intervention].
AB  - A design proposal for a HQCAS Hospital Quality Control and Assessment System of
      the nutritional and feeding care processes conducted in a hospital environment is
      presented in this article. The design proposal is accompanied of the results of
      inspections conducted by the hospital NST Nutritional Support Group between 2005
      2010. The system design includes quality policies that should rule the useful and
      safe conduction of such processes, the recording and documentary foundations of
      the System, and the quality control and assessment exercises for the continuous
      verification of such established policies. The current state of the conduction of
      these processes was documented from secondary records opened by the NST after
      satisfying consultation requests from the medical care teams of the institution.
      Inspections conducted by the NST revealed that less than half of clinical charts
      contained information minimally enough for elaborating nutritional judgments,
      almost one-fifth of the assisted patients were on Nils Per Oris, for whom no
      nutritional support schemes were prescribed, and a low prescription and usage of
      artificial nutrition schemes. Corrective measures adopted by the NST served to
      significantly increase the rates of successful completion of inspected processes.
      Quality assurance of feeding and nutritional care processes is a practical as
      well as an intellectual activity subjected to constant remodeling, in order to
      always warrant the fulfillment of quality policies advanced by the NST, and thus,
      that the patient benefits from the prescribed nutritional intervention strategy.

PMID- 23114953
TI  - Lipid profile and cardiovascular risk in anorexia nervosa; the effect of
      nutritional treatment.
AB  - OBJECTIVE: The aim of this study was to explore the lipid profile in patients
      with anorexia nervosa (AN), and the changes with refeeding. METHODS: The sample
      comprised 102 AN outpatients (mean age 22.32 +/- 3.17). Blood tests, after 12
      hour overnight fast, were performed before refeeding (M(0)) and after weight
      restoration (M(1)). Total cholesterol (TC), high-density lipoproteins (HDL), low
      density lipoproteins (LDL) and triglycerides (TRG) were determined and the
      following cardiovascular risk markers were calculated: LDL/HDL and TC/HDL ratios.
      These cut-off points were considered: TC < 200 mg/dl; HDL > 40 mg/dl; LDL < 100
      mg/dl and TRG < 150 mg/dl. RESULTS: The time leading to weight restoration was
      8.16 +/- 7.35 months. Considering patients with scores higher and lower than the
      corresponding cut-off points, X2-test revealed a significant difference (M(0)
      M(1)) in case of TC (p < 0.05) as well as between LDL/HDL(0) and LDL/HDL(1) (p <
      0.05) and between TC/HDL(0) and TC/HDL(1) (p < 0.01). Significant differences
      were found between HDL(0) and HDL(1) (p < 0.01) and between TRG(0) and TRG(1) (p
      < 0.01). Significant and negative associations between BMI(0) and TC(0) (r = 
      0.331; p < 0.05) and between TRG(0) and HDL(0) (r = -0.387; p < 0.05) were found.
      The association between TRG(1) and LDL(1) was significant and positive.
      DISCUSSION: Weight restoration tends to decrease the TC/HDL and LDL/HDL ratios
      despite a considerable percentage of patients maintain scores on the different
      variables of the lipid profile usually considered at risk.

PMID- 23114954
TI  - Assessment of food consumption, energy and protein intake in the meals offered in
      four Spanish nursing homes.
AB  - BACKGROUND/OBJECTIVE: The elderly, and especially those attending nursing homes,
      are at great risk from certain nutritional deficiencies. The aim of this study
      was to examine the percentage of energy wasted, energy and protein intake and
      percentage consumed of meal offered by a group of healthy institutionalized
      elderly in four nursing homes in Spain. DESIGN AND METHODS: This was a
      multicentre observational study of a sample of the institutionalized population
      over the age of 65. Our final sample comprised a total of 62 individuals. Dietary
      data were collected using double weight method for each meal during 21 days. We
      calculated the following consumption variables: percentage of food consumed (%
      food consumed) for each subject in each meal. We also calculated the energy
      intake (kcal/day), the wasted energy (kcal/day), the protein intake (g protein/
      day) and the energy density (kcal/g meal) for each of the meals eaten. To analyse
      the overall differences we used analysis of variance test (ANOVA). The
      significance level used was 0.05 (p < 0.05). RESULTS: The largest meals were
      lunch (781 g/day [728.4, 833.6]) and dinner (653 g/day [612.1, 693.9]). The
      percentage of total consumption was 81.9% [79.3, 84.6]. The average energy
      consumption was 1,575.4 kcal/day [1,508.3, 1,642.6]. The percentage of caloric
      distribution varied depending on the center. The highest percentage of wasted
      food was found in the main meals. Forty four percent did not consume enough
      energy to meet the recommended intakes. Protein intake was 63.6 g protein / day
      [61.2, 66.1]. 12.5% of women and 4.55% of men did not consume the recommended
      intakes for the elderly. Breakfast and the bedtime snack had the highest energy
      density with 1.10 [0.9, 1.25] and 1.04 [0.9, 1.08] kcal/g food served
      respectively [Energy density]. DISCUSION/CONCLUSIONS: The best strategy for
      increasing the energy intake of the institutionalized elderly without raising the
      amount of food that is rejected may be to provide higher energy density foods in
      the same serving sizes.

PMID- 23114955
TI  - [Pica diagnosis during pregnancy and micronutrient dificiency in Argentine
      women].
AB  - OBJECTIVE: To evaluate by biochemical parameters iron and zinc nutritional status
      in women with and without pica diagnosis during pregnancy. METHODOLOGY: During
      puerperium 109 women were evaluated at Fiorito Hospital, Argentina. Pica
      diagnosis was made in 42 women while 67 did not refer the practice. Fasting blood
      samples were obtained and analyzed in a hematology analyzer for values of red
      blood cells, hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin,
      mean corpuscular hemoglobin concentration, and hematocrit. Serum zinc and
      erythrocyte zinc was analyzed by atomic absorption spectrophotometry. RESULTS:
      Substances consumed during pica practice were: earth, ice, brick, paper,
      desinfectant and dog food. Women with pica diagnosis had higher a rate of family
      history of pica and personal antecedents of pica in childhood (OR: 15.9).
      Sociodemographic and anthropometric characteristics and neonatal birth weight
      were similar between both groups, although women with pica diagnosis had lower
      values in mean corpuscular volume (p = 0,008), mean corpuscular hemoglobin (p =
      0,009) and erythrocyte zinc (0,008). Applying a logistic regression model,
      erythrocyte zinc was the only biochemical indicator associated with pica practice
      (p = 0,028). CONCLUSIONS: At puerperium, women with pica during pregnancy could
      have lower levels in biochemical parameters for iron and zinc status so we
      suggest that early diagnosis of pica could help to identify micronutrient
      deficient.

PMID- 23114956
TI  - Relationship between body mass index with dietary fiber intake and skinfolds-
      differences among bodybuilders who train during morning and nocturne period.
AB  - BACKGROUND: The prevalence of overweight individuals has increased in recent
      years. Moreover, the importance of a healthy diet is associated with the practice
      of physical activity and attempt to verify the achievement of physical exercise
      influences on food choice. However, it relationship between food intake and
      physical activity have not been studied. AIM: To evaluate if the period in which
      the trainings are conducted, morning and nocturne, interfere qualitatively and
      quantitatively in food consumption as well as verify possible associations
      between anthropometric profiles and dietary habits. METHODS: We collected data
      from 33 adult volunteers, between men and women, practitioners of bodybuilding.
      RESULTS: A total of 33 volunteers were interviewed (18 (54.5%) were men and 15
      (45.5%) were women). Regarding anthropometric data, it turns out that that the
      volunteers of the two periods had similar characteristics, differentiating only
      weight. The consumption of nutritional supplements was observed in 30.77% of the
      practitioners in the morning period vs. 35% for the nocturne. Considering
      macronutrient intake, there was a significant difference in the consumption of
      protein between the periods. The consumption during nocturne period was greater
      (126 +/- 5% of the daily requirement) than the morning period (115.7 +/- 2%). As
      for micro-nutrients, calcium intake was greater among men when compared to women.
      There was a positive correlation between the BMI, and arm circumference for
      practitioners of the morning period. CONCLUSION: This study show that the
      practitioners who train in the morning have quietly better eating habits than
      those in the nocturne period, however both are inappropriate.

PMID- 23114957
TI  - [Alcoholic ketoacidosis and reversible neurological complications due to
      hypophosphataemia].
AB  - A 57-year-old man with chronic alcoholism was admitted to our hospital due to
      disturbance of consciousness and polyradiculitis. Laboratory examination revealed
      metabolic acidosis, hypokalemia and hypophosphataemia. Alcoholic ketoacidosis is
      a common disorder in alcoholic patients. All patients present with a history of
      heavy alcohol misuse, preceding a bout of particularly excesive intake, which had
      been terminated by nausea, vomiting and abdominal pain. The most important
      laboratory results are: normal or low glucose level, metabolic acidosis with a
      raised anion GAP, low or absent blood alcohol level and urinary ketones. The
      greatest threats to patients are: hypovolemia, hypokaliemia, hypoglucemia and
      acidosis. Alcohol abuse may result in a wide range of electrolyte and acid-base
      disorders including hypophosphataemia, hypomagnesemia, hypocalcemia, hypokalemia,
      metabolic acidosis and respiratory alkalosis. Disturbance of consciousness in
      alcoholic patients is observed in several disorders, such drunkenness, Wernicke
      encephalopathy, alcohol withdrawal syndrome, central pontine myelinolysis,
      hepatic encephalopathy, hypoglucemia and electrolyte disorders.

PMID- 23114958
TI  - [Persistent chylothorax in patient with lymphangioleiomyomatosis].
AB  - Lymphangioleiomyomatosis (LAM) is a rare disease that affects women in fertile
      age and presents a systemic progressive evolution, being the lung and the
      mediastinic lymph nodes the most affected organs. The pulmonary disease is
      characterized by dyspnea, pleural effusion, hemoptysis and spontaneous
      pneumothorax, being the chylothorax a frequent complication in the course of this
      disease, appearing in up to 30% of cases. The treatment of chylothorax is not
      standardized and it is necessary a multidisciplinary approach: nutritional,
      pharmacological, respiratory and even surgery. These patients present high risk
      of malnutrition due to the constant loss of chyle, therefore a suitable
      nutritional management is essential to avoid more complications.

PMID- 23114959
TI  - [Pilot study of intravenous fluid therapy management in adult patients at a
      tertiary care hospital].
AB  - The purpose of intravenous fluid therapy (IFT) is to maintain or restore internal
      equilibrium by administering fluids and/or different electrolyte components. Its
      correct use and the prevention of complications arising from their misuse depend
      on the knowledge of the medical team on this subject. We analyzed this issue in
      different clinical areas of a tertiary hospital. MATERIAL AND METHODS: We
      performed a descriptive cross-sectional pilot study via a questionnaire given to
      physicians specializing in internal medicine (IM) and digestive system surgery
      (SDS) who perform clinical practice in hospital units with unit dose drug
      dispensing system. We designed an anonymous questionnaire with 25 questions
      relative to knowledge of theory and practices, as well as the opinion of
      physicians regarding IFT. We evaluated the association between nominal
      qualitative variables with the Chi-square or Fisher's exact test. The behavior of
      the quantitative variables was assessed using the t-student test. The analysis of
      the data was generated using SAS/STAT, Version 9. RESULTS: 28 questionnaires were
      collected from 13 surgeons and 15 digestive interns. Over 40% of specialists
      considered further education in IFT a necessity , especially regarding its
      prescription (SDS: 61.54%, IM: 71.43%). No statistically significant differences
      were found between the specialties in terms of perceived frequency of
      complications associated with IFT or in the frequency indication with the
      exception of hypovolemic shock, which is considered to be more prevalent in
      gastrointestinal surgery (p = 0.046). 90% of professionals prefer an
      individualized prescription. Statistically significant differences in terms of
      scores in the area of knowledge, with IM physicians achieving the highest scores
      (p = 0.014). There were also differences in attitude but they are not significant
      (p = 0.162). Knowledge of intravenous fluid increases with years of clinical
      experience (Spearman correlation coefficient = 0.386, p = 0.047). CONCLUSIONS:
      The professionals who prescribe IFT perceive the need to design IFT training
      programs, together with the production of guides and consensus protocols.

PMID- 23114960
TI  - [Efficacy and safety of adjuvant octreotide with parenteral nutrition for
      conservative treatment of chylothorax].

PMID- 23114961
TI  - [Body composition analysis in adult women with systemic lupus erythematosus].

PMID- 23114962
TI  - Hemodynamic shear stress characteristic of atherosclerosis-resistant regions
      promotes glycocalyx formation in cultured endothelial cells.
AB  - The endothelial glycocalyx, a glycosaminoglycan layer located on the apical
      surface of vascular endothelial cells, has been shown to be important for several
      endothelial functions. Previous studies have documented that the glycocalyx is
      highly abundant in the mouse common carotid region, where the endothelium is
      exposed to laminar shear stress, and it is resistant to atherosclerosis. In
      contrast, the glycocalyx is scarce or absent in the mouse internal carotid sinus
      region, an area exposed to nonlaminar shear stress and highly susceptible to
      atherosclerosis. On the basis of these observations, we hypothesized that the
      expression of components of the endothelial glycocalyx is differentially
      regulated by distinct hemodynamic environments. To test this hypothesis, human
      endothelial cells were exposed to shear stress waveforms characteristic of
      atherosclerosis-resistant or atherosclerosis-susceptible regions of the human
      carotid, and the expression of several components of the glycocalyx was assessed.
      These experiments revealed that expression of several components of the
      endothelial glycocalyx is differentially regulated by distinct shear stress
      waveforms. Interestingly, we found that heparan sulfate expression is increased
      and evenly distributed on the apical surface of endothelial cells exposed to the
      atheroprotective waveform and is irregularly present in cells exposed to the
      atheroprone waveform. Furthermore, expression of a heparan sulfate proteoglycan,
      syndecan-1, is also differentially regulated by the two waveforms, and its
      suppression mutes the atheroprotective flow-induced cell surface expression of
      heparan sulfate. Collectively, these data link distinct hemodynamic environments
      to the differential expression of critical components of the endothelial
      glycocalyx.

PMID- 23114963
TI  - Interleukin-6 promotes myogenic differentiation of mouse skeletal muscle cells:
      role of the STAT3 pathway.
AB  - Myogenic differentiation of skeletal muscle cells is characterized by a sequence
      of events that include activation of signal transducer and activator of
      transcription 3 (STAT3) and enhanced expression of its target gene Socs3.
      Autocrine effects of IL-6 may contribute to the activation of the STAT3-Socs3
      cascade and thus to myogenic differentiation. The importance of IL-6 and STAT3
      for the differentiation process was studied in C2C12 cells and in primary mouse
      wild-type and IL-6(-/-) skeletal muscle cells. In differentiating C2C12
      myoblasts, the upregulation of IL-6 mRNA expression and protein secretion started
      after increased phosphorylation of STAT3 on tyrosine 705 and increased mRNA
      expression of Socs3 was observed. Knockdown of STAT3 and IL-6 mRNA in
      differentiating C2C12 myoblasts impaired the expression of the myogenic markers
      myogenin and MyHC IIb and subsequently myotube fusion. However, the knockdown of
      IL-6 did not prevent the induction of STAT3 tyrosine phosphorylation. The IL-6
      independent activation of STAT3 was verified in differentiating primary IL-6(-/-)
      myoblasts. The phosphorylation of STAT3 and the expression levels of STAT3,
      Socs3, and myogenin during differentiation were comparable in the primary
      myoblasts independent of the genotype. However, IL-6(-/-) cells failed to induce
      MyHC IIb expression to the same level as in wild-type cells and showed reduced
      myotube formation. Supplementation of IL-6 could partially restore the fusion of
      IL-6(-/-) cells. These data demonstrate that IL-6 depletion during myogenic
      differentiation does not reduce the activation of the STAT3-Socs3 cascade, while
      IL-6 and STAT3 are both necessary to promote myotube fusion.

PMID- 23114964
TI  - Combined in vivo and in silico investigations of activation of glycolysis in
      contracting skeletal muscle.
AB  - The hypothesis was tested that the variation of in vivo glycolytic flux with
      contraction frequency in skeletal muscle can be qualitatively and quantitatively
      explained by calcium-calmodulin activation of phosphofructokinase (PFK-1).
      Ischemic rat tibialis anterior muscle was electrically stimulated at frequencies
      between 0 and 80 Hz to covary the ATP turnover rate and calcium concentration in
      the tissue. Estimates of in vivo glycolytic rates and cellular free energetic
      states were derived from dynamic changes in intramuscular pH and phosphocreatine
      content, respectively, determined by phosphorus magnetic resonance spectroscopy
      ((31)P-MRS). Computational modeling was applied to relate these empirical
      observations to understanding of the biochemistry of muscle glycolysis. Hereto,
      the kinetic model of PFK activity in a previously reported mathematical model of
      the glycolytic pathway (Vinnakota KC, Rusk J, Palmer L, Shankland E, Kushmerick
      MJ. J Physiol 588: 1961-1983, 2010) was adapted to contain a calcium-calmodulin
      binding sensitivity. The two main results were introduction of regulation of PFK
      1 activity by binding of a calcium-calmodulin complex in combination with
      activation by increased concentrations of AMP and ADP was essential to
      qualitatively and quantitatively explain the experimental observations. Secondly,
      the model predicted that shutdown of glycolytic ATP production flux in muscle
      postexercise may lag behind deactivation of PFK-1 (timescales: 5-10 s vs. 100-200
      ms, respectively) as a result of accumulation of glycolytic intermediates
      downstream of PFK during contractions.

PMID- 23114965
TI  - Effects of ACE inhibition and ANG II stimulation on renal Na-Cl cotransporter
      distribution, phosphorylation, and membrane complex properties.
AB  - The renal distal tubule Na-Cl cotransporter (NCC) reabsorbs <10% of the filtered
      Na(+) but is a key control point for blood pressure regulation by angiotensin II
      (ANG II), angiotensin-converting enzyme inhibitors (ACEI), and thiazide
      diuretics. This study aimed to determine whether NCC phosphorylation (NCCp) was
      regulated by acute (20-30 min) treatment with the ACEI captopril (12 MUg/min * 20
      min) or by a sub-pressor dose of ANG II (20 ng.kg(-1).min(-1)) in Inactin
      anesthetized rats. By immuno-EM, NCCp was detected exclusively in or adjacent to
      apical plama membranes (APM) in controls and after ACEI or ANG II treatment,
      while NCC total was detected in both APM and subapical cytoplasmic vesicles (SCV)
      in all conditions. In renal homogenates, neither ACEI nor ANG II treatment
      altered NCCp abundance, assayed by immunoblot. However, by density gradient
      fractionation we identified a pool of low-density APM in which NCCp decreased 50%
      in response to captopril and was restored during ANG II infusion, and another
      pool of higher-density APM that responded reciprocally, indicative of regulated
      redistribution between two APM pools. In both pools, NCCp was preferentially
      localized to Triton-soluble membranes. Blue Native gel electrophoresis
      established that APM NCCp localized to ~700 kDa complexes (containing gamma
      adducin) while unphosphorylated NCC in intracellular membranes primarily
      localized to ~400 kDa complexes: there was no evidence for native monomeric or
      dimeric NCC or NCCp. In summary, this study demonstrates that phosphorylated NCC,
      localized to multimeric complexes in the APM, redistributes in a regulated manner
      within the APM in response to ACEI and ANG II.

PMID- 23114966
TI  - Determination of the membrane topology of lemur tyrosine kinase 2 (LMTK2) by
      fluorescence protease protection.
AB  - Lemur tyrosine kinase 2 (LMTK2) is a novel membrane-anchored kinase reported to
      be involved in several normal and pathophysiological conditions, including
      endosomal membrane recycling, prostate cancer, and neurodegeneration. In this
      study, we have investigated the topology and orientation of LMTK2 within cellular
      membranes utilizing fluorescence protease protection. Appending the green
      fluorescent protein to either the amino or carboxyl terminus of LMTK2, we were
      able to determine which side of intracellular membrane these regions were
      located. Our results indicate that LMTK2 is an integral membrane protein in which
      both the amino and carboxyl termini are exposed to the cytoplasm. Moreover, this
      topology places the kinase active site within the cytoplasm.

PMID- 23114967
TI  - Heme modulates intestinal epithelial cell activation: involvement of NADPHox
      derived ROS signaling.
AB  - In many gut chronic inflammatory conditions, intestinal epithelium (IE) is
      deprived of the protection of the mucus secreted by IE-specialized cells. In
      these events, bleeding and subsequent lysis of erythrocytes are common. This may
      lead to the release of high amounts of heme in the intestinal lumen, which
      interacts with IE. Previous works from our group have shown that heme itself is a
      proinflammatory molecule, activating a number of phlogistic signaling events in a
      nicotinamide adenine dinucleotide phosphate oxidase (NADPHox)-dependent manner.
      In this study, we aim to evaluate the effects of heme upon a well-established
      nontransformed small intestine epithelial cell lineage (IEC 6). Our results show
      that free heme evokes intracellular reactive oxygen species (ROS) production by
      IEC 6 cells, which is inhibited both by pharmacological inhibition with
      diphenyleneiodonium (10 MUM), a NADPHox inhibitor, and small interfering RNA
      mediated suppression of NOX1, a constitutive NADPHox isoform present in
      intestinal epithelial cells. Focal adhesion kinase phosphorylation and actin
      cytoskeleton polymerization are also induced by heme in a NADPHox-dependent
      manner. Heme increases monolayer permeability and redistributes key modulators of
      cell-cell adhesion as zona occludens-1 and E-cadherin proteins via NADPHox
      signaling. Heme promotes IEC 6 cell migration and proliferation, phenomena also
      regulated by NADPHox-derived ROS. Heme, in NADPHox-activating concentrations, is
      able to induce mRNA expression of IL-6, a cytokine implicated in inflammatory and
      tumorigenic responses. These data indicate a prominent role for heme-derived
      signaling in the pathophysiology of intestinal mucosa dysfunction and address an
      important role of NADPHox activity on the pathogenesis of intestinal inflammatory
      conditions.

PMID- 23114968
TI  - Subacute methotrexate-related leukoencephalopathy with stroke-like presentation.

PMID- 23114969
TI  - Effect of soil salinity on physiological characteristics of functional leaves of
      cotton plants.
AB  - This study analyzes the effects of soil salinity on fatty acid composition,
      antioxidative enzyme activity, lipid peroxidation, and photosynthesis in
      functional leaves during the flowering and boll-forming stages of two cotton
      cultivars, namely, CCRI-44 (salt-tolerant) and Sumian 12 (salt-sensitive), grown
      under different soil salinity conditions. Saturated (C16:0 and C18:0) and
      unsaturated fatty acid (FA) contents (C18:1), as well as superoxide dismutase
      activity increased, whereas high-unsaturated FA (C18:2 and C18:3) decreased, with
      the increase in soil salinity. The production of malondialdehyde increased with
      increasing lipoxygenase (LOX) activity, indicating that LOX catalyzed FA
      peroxidation under salt stress. Soil salinity had no significant effect on
      catalase (CAT) and peroxidases (POD) activity in the salt-sensitive cultivar
      Sumian 12, but significantly increased CAT and POD activities in the salt
      tolerant cultivar CCRI-44. Net photosynthesis and stomatal conductance of the
      cotton cultivars decreased in response to salt stress; however, CCRI-44 showed a
      smaller reduction in photosynthesis than Sumian 12. The results indicated that
      stomatal apparatus limited leaf photosynthetic capacity in the salinity-treated
      plants of both cultivars. The net photosynthetic rate, maximum photochemical
      efficiency, and photochemical quantum yield of the cotton functional leaves
      showed positive correlation with double-bond index (DBI). These results suggested
      that salt stress caused DBI reduction and decreased the photochemical conversion
      efficiency of solar radiation and, thereby resulting in lower net photosynthetic
      rates.

PMID- 23114970
TI  - Recognition of two major clades and early diverged groups within the subfamily
      Cyperoideae (Cyperaceae) including Korean sedges.
AB  - We aim to present phylogenetic major groups within the subfamily Cyperoideae
      (Cyperaceae) on the basis of three molecular data sets; nuclear ribosomal
      internal transcribed spacer and 5.8S ribosomal RNA region, the ribulose-1, 5
      bisphosphate carboxylase/oxygenase large subunit gene, and trnL intron and trnL-F
      intergenic spacer. Three molecular data and two combined data sets were used to
      obtain robust and detailed phylogenetic trees by using maximum parsimony and
      Bayesian inference, respectively. We analyzed 81 genera and 426 species of
      Cyperaceae, including Korean species. We suggest one early diverged group (EDGs),
      and two major clades (FAEC and SDC) within the subfamily Cyperoideae. And the
      clade EDGs comprises six tribes (Schoeneae, Bisboeckelereae, Sclerieae,
      Cryptangieae, Trilepideae, and Rhynchosporeae) at the basal nodes of Cyperoideae.
      The FAEC clade (posterior probability [PP]/bootstrap value [BS] = 1.00/85)
      comprises four tribes (Fuireneae, Abildgaardieae, Eleocharideae, Cypereae), and
      the SDC clade (PP/BS = 1.00/86) comprises three tribes (Scirpeae, Dulichieae,
      Cariceae). These three clades used for phylogenetic groups in our study will be
      useful for establishing the major lineage of the sedge family. The phylogeny of
      Korean sedges was also investigated within the whole phylogeny of Cyperaceae. The
      20 genera of Korean sedges were placed in 10 tribes forming 14 clades.

PMID- 23114971
TI  - Acute improvement in insulin resistance after laparoscopic Roux-en-Y gastric
      bypass: is 3 days enough to correct insulin metabolism?
AB  - BACKGROUND: Although medium- to long-term improvement in insulin resistance and
      T2DM after Roux-en-Y gastric bypass (RYGB) is well documented, few studies have
      analyzed the acute effects after surgery. Understanding these effects might help
      explain the physiologic adjustments after surgery and help in managing insulin
      resistance and controlling the hypoglycemic treatment for bariatric patients.
      METHODS: We recruited a prospective cohort of 55 consecutive female patients that
      underwent primary laparoscopic RYGB between January and June/2011. Blood samples
      were collected preoperatively and at the first, third, and fifth post-operative
      days after an overnight fast. RESULTS: There was a significant increase in
      homeostasis model assessment for insulin resistance (HOMA-IR) on day 1 (2.36 vs
      3.12; p = 0.032), followed by a rapid decrease from day 3 onward (3.12 vs 1.70;
      <0.001). We found a statistically significant difference (p < 0.05) at all time
      points compared with baseline. HOMA-IR levels at POD5 were 47 % lower than
      baseline values and were not significantly different from values at 6 months
      (1.24 vs 0.93; p = 0.09). The blood levels of glucose and insulin closely matched
      those of HOMA-IR. CONCLUSIONS: RYGB results in a rapid improvement in insulin
      resistance and a clinically significant decrease in fasting glucose and insulin
      levels. This improvement is significant at the 3rd post-operative day, and by the
      5th day, patients express insulin resistance levels that are similar to those
      expressed at 6 months after surgery. This work highlights the acute metabolic
      impact of surgery. Understanding the behavior of insulin and glucose after
      surgery might improve our knowledge of the pathophysiology of diabetes and lead
      to novel therapies and tailored surgical approaches.

PMID- 23114972
TI  - Optical non-contact localization of liquid-gas interfaces on disk during rotation
      for measuring flow rates and viscosities.
AB  - We present a novel technique for the spatio-temporally resolved localization of
      liquid-gas interfaces on centrifugal microfluidic platforms based on total
      internal reflection (TIR) at the channel wall. The simple setup consists of a
      line laser and a linear image sensor array mounted in a stationary instrument.
      Apart from identifying the presence of usually unwanted gas bubbles, the here
      described online meniscus detection allows to measure liquid volumes with a high
      precision of 1.9%. Additionally, flow rates and viscosities (range: 1-12 mPa s,
      precision of 4.3%) can be sensed even during rotation at frequencies up to 30 Hz.

PMID- 23114973
TI  - Is there an optimal level of open-endedness in prebiotic evolution?
AB  - In this paper we explore the question of whether there is an optimal set up for a
      putative prebiotic system leading to open-ended evolution (OEE) of the events
      unfolding within this system. We do so by proposing two key innovations. First,
      we introduce a new index that measures OEE as a function of the likelihood of
      events unfolding within a universe given its initial conditions. Next, we apply
      this index to a variant of the graded autocatalysis replication domain (GARD)
      model, Segre et al. (P Natl Acad Sci USA 97(8):4112-4117, 2000; Markovitch and
      Lancet Artif Life 18(3), 2012), and use it to study--under a unified and concise
      prebiotic evolutionary framework--both a variety of initial conditions of the
      universe and the OEE of species that evolve from them.

PMID- 23114974
TI  - Congenital diaphragmatic hernia.

PMID- 23114975
TI  - Etiological and pathogenic factors in congenital diaphragmatic hernia.
AB  - Congenital diaphragmatic hernia (CDH) is a congenital anomaly associated with an
      increased mortality and morbidity. In this article, we review the currently known
      etiological and pathogenic factors in CDH.

PMID- 23114976
TI  - Surgical techniques in congenital diaphragmatic hernia.
AB  - In congenital diaphragmatic hernia (CDH), surgery is considered the less
      controversial part of the treatment. However, surgical strategies for CDH are
      widely disparate and several surgical aspects are still being discussed. The aim
      of this review is to describe the current surgical treatment of CDH, examining
      its most controversial issues.

PMID- 23114977
TI  - Minimal access surgery for repair of congenital diaphragmatic hernia: is it
      advantageous?--An open review.
AB  - INTRODUCTION: Congenital diaphragmatic hernia (CDH) is a congenital life
      threatening condition requiring surgical repair in the neonatal period. Minimal
      access surgery (MAS) is gaining ground on the classical open approach by
      laparotomy or thoracotomy as it minimizes damage to the abdominal or thoracic
      wall. Using an open review of the literature, we aimed to determine whether MAS
      is safe and effective in treating CDH. Furthermore, we provide selection criteria
      for the optimal surgical approach, laid down in a decision algorithm. METHODS: An
      online search of MEDLINE was performed (May 2012), followed by a citations
      search. All study types except case reports describing open and/or MAS repair of
      Bochdalek CDH were eligible. Primary outcome data, for example, surgical
      complications and mortality, were recorded, as well as secondary outcome
      measures, for example, operative time, duration of postoperative ventilation,
      tolerance of enteral nutrition, and total length of stay (LOS) in hospital.
      Analysis was performed in accordance with the standards of the Cochrane Handbook
      for Systematic Reviews of Interventions. RESULTS: We identified 15 relevant
      studies, 5 of them describing MAS only and 10 comparing MAS to open repair of
      CDH. Numbers of included patients and selection criteria for MAS varied widely.
      Most studies have methodological limitations, such as the use of retrospective
      data or historical control groups. ECMO treatment and patch use were more
      frequent in the open repair group (both p < 0.0001). Recurrence risk seemed to be
      increased in the MAS group. The need for conversion in MAS series ranged widely,
      from 3.4 to 75.0%. The risk of general surgical complications did not vary
      between groups. Mortality seemed to be less in the MAS group. Operative time
      seemed to be longer in the MAS group. Duration of postoperative ventilation and
      total LOS appeared to be reduced in this group and patients returned quicker to
      enteral nutrition. CONCLUSIONS: We demonstrate that MAS for diaphragmatic hernia
      appears to be safe in terms of complications and mortality. Besides, it is
      associated with faster postoperative recovery. Growing experience with this
      technique is expected to lower the recurrence risk and to shorten the operative
      time. These findings should be interpreted cautiously because of methodological
      limitations of the studies included. Selection criteria used in various studies
      are associated with an important risk of selection bias. Nonetheless, these
      criteria can be used to identify patients who will benefit most from MAS.

PMID- 23114978
TI  - Management of pulmonary hypertension in neonates with congenital diaphragmatic
      hernia.
AB  - Pulmonary hypertension associated with congenital diaphragmatic hernia is still
      one of the major challenges in neonatal intensive care units. Several relevant
      pathways in its pathogenesis have been described and studied, but the absence of
      well-designed randomized controlled trials and the scattered data on the
      pharmacokinetics and pharmacodynamics of most of the drugs used in these patients
      hamper progress significantly. This review aims to give an overview of current
      management strategies in the antenatal and neonatal phase, and provides founded
      clinical recommendations.

PMID- 23114979
TI  - Morbidity and long-term follow-up in CDH patients.
AB  - Overall survival of congenital diaphragmatic hernia (CDH) patients has increased
      since the widespread implementation of delayed operative repair with
      extracorporeal membrane oxygenation/gentle ventilation strategies starting in the
      mid-1990s. With the improvements in survival, CDH survivorship has been marked by
      increased morbidity with a greater need for monitoring and supportive
      interventions in infancy and early childhood. The multisystem morbidity and
      complexity of care for these patients mandate the dedicated resources and focus
      of medical specialties to ensure that the neurodevelopmental, cardiopulmonary,
      nutritional, and surgical sequelae of CDH are properly addressed. In this
      article, we will discuss the experience of CDH centers that offer long-term CDH
      follow-up as well as the patients' morbidities that require active monitoring
      until transition to adult care.

PMID- 23114980
TI  - Regenerative medicine for congenital diaphragmatic hernia: regeneration for
      repair.
AB  - Regenerative medicine has developed recently as a new field of science aiming at
      restoring organ and tissue damage through the use of autologous constructs.
      Cellular therapies and relatively simple tissue engineering reconstructions have
      recently been successfully applied into patients. For babies born with congenital
      diaphragmatic hernia, regenerative medicine may play a role both in developing a
      myogenic patch capable of restoring muscle function and promoting regeneration of
      hypoplastic lungs that characterised those patients. The latter is particularly
      attractive because it may change the long-term outcome of those children. We aim
      here to discuss recent advancement in the field, looking in particular at the
      future clinical prospective of those exciting therapeutic strategies.

PMID- 23114981
TI  - The eroding principle of justice in teaching medical professionalism.
AB  - This article examines the difficulties encountered in teaching professionalism to
      medical students in the current social and political climate where economic
      considerations take top priority in health care decision making. The conflict
      between the commitment to advocate at all times the interests of one's patients
      over one's own interests is discussed. With personal, institutional, tech
      industry, pharmaceutical industry, and third-party payer financial imperatives
      that stand between patients and the delivery of health care, this article
      investigates how medical ethics instructors are to teach professionalism in a
      responsible way that does not avoid dealing with the principle of justice.

PMID- 23114982
TI  - Genome-wide investigation of gene-environment interactions in colorectal cancer.
AB  - Colorectal cancer (CRC), one of the most frequent neoplasias worldwide, has both
      genetic and environmental causes. As yet, however, gene-environment (G * E)
      interactions in CRC have been studied mostly for a small number of candidate
      genes only. Therefore, we investigated the possible interaction, in CRC etiology,
      between single-nucleotide polymorphisms (SNPs) on the one hand, and overweight,
      smoking and alcohol consumption on the other, at a genome-wide level. To this
      end, we adopted a two-tiered approach comprising a case-only screening stage I
      (314 cases) and a case-control validation stage II (259 cases, 1,002 controls).
      Interactions with the smallest p value in stage I were verified in stage II using
      multiple logistic regression analysis adjusted for sex and age. In addition, we
      specifically studied known CRC-associated SNPs for possible G * E interactions.
      Upon adjustment for sex and age, and after allowing for multiple testing,
      however, only a single SNP (rs1944511) was found to be involved in a
      statistically significant interaction, namely with overweight (multiplicity
      corrected p = 0.042 in stage II). Several other G * E interactions were nominally
      significant but failed correction for multiple testing, including a previously
      reported interaction between rs9929218 and alcohol consumption that also emerged
      in our candidate SNP study (nominal p = 0.008). Notably, none of the interactions
      identified in our genome-wide analysis was with a previously reported CRC
      associated SNP. Our study therefore highlights the potential of an "agnostic"
      genome-wide approach to G * E analysis.

PMID- 23114983
TI  - Identification of a replication initiation protein of the pVV8 plasmid from
      Thermus thermophilus HB8.
AB  - Recently, the extremely thermophilic bacterium Thermus thermophilus HB8 has been
      demonstrated to harbor a circular plasmid designated by pVV8 in addition to two
      well-known plasmids, pTT8 and pTT27, and its entire sequence has been determined.
      The absence of any obvious replication initiation gene in the 81.2 kb plasmid
      prompted us to isolate its minimum replicon. By in vivo replication assays with
      fragments deleted in a stepwise manner, a minimum replicon containing a single
      ORF, TTHV001, was identified. A protein encoded by TTHV001 showed no amino acid
      sequence similarity to other function-known proteins. As the results of in vivo
      and in vitro experiments strongly suggested that the TTHV001 protein was involved
      in the replication initiation of pVV8, the protein and the gene were referred to
      as RepV and repV, respectively. The RepV protein binds to an inverted repeat
      sequence within its own repV gene and then triggers the unwinding of the DNA
      duplex in an A + T-rich region located just downstream from the inverted repeat.
      The in vivo replication assays with minimum replicon mutants in the RepV binding
      site or the unwinding region demonstrated that the unwinding in the region by the
      RepV binding was essential for pVV8 replication initiation.

PMID- 23114984
TI  - Sonographic abnormality of the substantia nigra in melanoma patients.
AB  - BACKGROUND: Evidence derived from large epidemiological studies suggests an
      association between Parkinson's disease (PD) and malignant melanoma. Transcranial
      sonography of the midbrain reveals an extended echogenic substantia nigra (SN)
      area in a high proportion of patients with PD. This characteristic, in the
      context of PD, may signal degeneration of dopaminergic nigrostriatal projection
      neurons. Demonstration of an increased prevalence of abnormal echogenic SN in
      melanoma patients could add weight to the hypothesis of an underlying common
      pathogenic pathway of both diseases. METHODS: This was a cross-sectional
      observational study. Transcranial sonography of the SN region was performed on 31
      patients suffering from malignant melanoma and 29 healthy participants. In
      addition, patients and controls were screened for motor and non-motor symptoms of
      PD. RESULTS: The echogenic SN area was abnormally extended in 42% of melanoma
      patients versus 7% of control subjects (chi(2) = 9.811, P = .002). Mean echogenic
      SN area (SN[R, L]) was significantly larger in melanoma patients than in controls
      (patients, 0.21 +/- 0.07 cm(2); controls, 0.15 +/- 0.04 cm(2) [mean +/- SD];
      unpaired t test, P < .001). CONCLUSIONS: These findings provide additional
      evidence in favor of a common pathogenic pathway of PD and malignant melanoma and
      raise the possibility that their association is closer than previously assumed.

PMID- 23114985
TI  - In situ forming, resorbable graft copolymer hydrogels providing controlled drug
      release.
AB  - In situ forming hydrogels are promising drug delivery vehicles due to their ease
      of delivery as liquids and their ability to be used in sites with irregular
      geometries. In this work, we report on in situ forming, resorbable hydrogels
      based on N-isopropylacrylamide (NIPAAm) as a fluid-like controlled release gel.
      These gels are the first resorbable NIPAAm-based gels providing controlled
      release without relying on affinity between the drug and device. Therefore, these
      gels provide a more flexible delivery system which can be used to deliver any
      drug at a controlled rate. The polymers contain repeat units of NIPAAm with (R)
      alpha-Acryloyloxy-beta,beta-dimethyl-gamma-butyrolactone (DBLA) and varying
      amounts of hydrophilic Jeffamine(r) M-1000 acrylamide (JAAm) grafts. The graft
      copolymer architecture allows the water content of the hydrogels to be tuned over
      a wide range while keeping the initial gelation temperature below body
      temperature. Incorporation of JAAm in the polymers led to greater water content,
      faster gel degradation, and reduced burst release. Sustained release of the
      antimicrobial drugs cefazolin and vancomycin (over about 5 and 7 days,
      respectively) was observed from gels containing an intermediate amount of grafts
      which combined reduced phase separation with a degradation time of 40 days. The
      degradation byproducts of one hydrogel formulation were cytocompatible to NIH 3T3
      fibroblasts at concentrations up to 2.5 wt %. This class of terpolymer hydrogels
      is a promising local delivery system for a wide variety of drugs, particularly
      for applications involving irregular geometries such as implant interfaces.

PMID- 23114986
TI  - Cytotoxic and immune-mediated killing of human colorectal cancer by reovirus
      loaded blood and liver mononuclear cells.
AB  - Reovirus is a promising oncolytic virus, acting by both direct and immune
      mediated mechanisms, although its potential may be limited by inactivation after
      systemic delivery. Our study addressed whether systemically delivered reovirus
      might be shielded from neutralising antibodies by cell carriage and whether virus
      loaded blood or hepatic innate immune effector cells become activated to kill
      colorectal cancer cells metastatic to the liver in human systems. We found that
      reovirus was directly cytotoxic against tumour cells but not against fresh
      hepatocytes. Although direct tumour cell killing by neat virus was significantly
      reduced in the presence of neutralising serum, reovirus was protected when loaded
      onto peripheral blood mononuclear cells, which may carry virus after intravenous
      administration in patients. As well as handing off virus for direct oncolytic
      killing, natural killer (NK) cells within reovirus-treated blood mononuclear
      cells were stimulated to kill tumour targets, but not normal hepatocytes, in a
      Type I interferon-dependent manner. Similarly, NK cells within liver mononuclear
      cells became selectively cytotoxic towards tumour cells when activated by
      reovirus. Hence, intravenous reovirus may evade neutralisation by serum via
      binding to circulating mononuclear cells, and this blood cell carriage has the
      potential to investigate both direct and innate immune-mediated therapy against
      human colorectal or other cancers metastatic to the liver.

PMID- 23114987
TI  - PaDEL-DDPredictor: open-source software for PD-PK-T prediction.
AB  - ADMET (absorption, distribution, metabolism, excretion, and toxicity)-related
      failure of drug candidates is a major issue for the pharmaceutical industry
      today. Prediction of PD-PK-T properties using in silico tools has become very
      important in pharmaceutical research to reduce cost and enhance efficiency. PaDEL
      DDPredictor is an in silico tool for rapid prediction of PD-PK-T properties of
      compounds from their chemical structures. It is free and open-source software
      that, has both graphical user interface and command line interface, can work on
      all major platforms (Windows, Linux, and MacOS) and supports more than 90
      different molecular file formats. The software can be downloaded from
      http://padel.nus.edu.sg/software/padelddpredictor.

PMID- 23114992
TI  - Separation of xylose oligomers using centrifugal partition chromatography with a
      butanol-methanol-water system.
AB  - Xylose oligomers are the intermediate products of xylan depolymerization into
      xylose monomers. An understanding of xylan depolymerization kinetics is important
      to improve the conversion of xylan into monomeric xylose and to minimize the
      formation of inhibitory products, thereby reducing ethanol production costs. The
      study of xylan depolymerization requires copious amount of xylose oligomers,
      which are expensive if acquired commercially. Our approach consisted of producing
      in-house oligomer material. To this end, birchwood xylan was used as the starting
      material and hydrolyzed in hot water at 200  degrees C for 60 min with a 4 %
      solids loading. The mixture of xylose oligomers was subsequently fractionated by
      a centrifugal partition chromatography (CPC) with a solvent system of
      butanol:methanol:water in a 5:1:4 volumetric ratio. Operating in an ascending
      mode, the butanol-rich upper phase (the mobile phase) eluted xylose oligomers
      from the water-rich stationary phase at a 4.89 mL/min flow rate for a total
      fractionation time of 300 min. The elution of xylose oligomers occurred between
      110 and 280 min. The yields and purities of xylobiose (DP 2), xylotriose (DP 3),
      xylotetraose (DP 4), and xylopentaose (DP 5) were 21, 10, 14, and 15 mg/g xylan
      and 95, 90, 89, and 68 %, respectively. The purities of xylose oligomers from
      this solvent system were higher than those reported previously using
      tetrahydrofuran:dimethyl sulfoxide:water in a 6:1:3 volumetric ratio. Moreover,
      the butanol-based solvent system improved overall procedures by facilitating the
      evaporation of the solvents from the CPC fractions, rendering the purification
      process more efficient.

PMID- 23114993
TI  - The Unified Multiple System Atrophy Rating Scale: intrarater reliability.
AB  - BACKGROUND: The Unified Multiple System Atrophy Rating Scale (UMSARS) was
      developed to provide a surrogate measure of disease progression in multiple
      system atrophy. In the present study, the intrarater agreement of the motor
      examination part of the UMSARS was determined. METHODS: All patients were first
      examined face to face, while being video-recorded, by two senior and two junior
      investigators. The patients' videotaped examinations were reevaluated after 3
      months. Intrarater reliability for each item was analyzed by kappa statistics.
      RESULTS: Overall weighted kappa (kappa) values were at least substantial or
      excellent for all UMSARS motor examination items, except for ocular motor
      dysfunction, which showed only moderate intrarater agreement. Intrarater
      reliability was comparable between senior and junior raters, with all kappa
      differences being <= 0.22. CONCLUSIONS: The motor examination part of the UMSARS
      was found to have satisfactory intrarater reliability in the present cohort.

PMID- 23114994
TI  - [Morphofunctional analysis of the efficiency of keratoplasty in the treatment of
      keratomycosis].
AB  - BACKGROUND: Keratoplastic surgery is an efficient treatment for serious
      keratomycosis, therefore these should be applied more often. The keratomycosis
      (mycotical keratitis) is a rare, but severe illness of the eye, since it is
      discovered often in a late stage and is challenging to cure. In these cases the
      accurately timed keratoplasty is very helpful. In this morphofunctional analysis
      the procedure of keratoplastic treatment and the efficiency of treatment of the
      keratomycosis were evaluated. METHODS: From January until November 2010 eight
      patients with microbiologically evident mycoses were treated operatively and
      conservatively by surgeons. The removed tissues were fixated in buffered formalin
      and embedded in paraffin. About 0.5 um thin paraffin sections were analysed
      histologically and histochemically and evaluated semiquantitatively.
      Postoperatively all patients have been treated antimycotically for 7 until 10
      days. RESULTS: The most important step for keratoplastic treatment was to remove
      the affected tissue completely and to treat with radical surgery in all cases. In
      this process the cornea was replaced by 3-mm and 5-mm pieces of sclera. The
      histological analysis of the eye after evisceration showed a complete destruction
      under the epithelium caused by the connective tissue-cellular proliferation.
      Postoperatively the topical, systemic and antimycotic therapy was continued for
      30 days. In three cases the cortisone therapy was used for three to six days
      after surgery. CONCLUSIONS: After successful keratoplastic treatment an
      improvement of the acuteness and either an improvement of vision about 60 to 70
      percent of the transparent regeneration were observed in all cases. To avoid
      recurrences for therapeutically keratoplastic treatment, radical removal of the
      injured tissue is necessary. Suppression of inflammations inside the treated eye
      was accelerated by systemic and topical application of corticosteroids, which
      influenced the condition of the transplants in a positive way.

PMID- 23114996
TI  - The relationship between dioxins and salivary steroid hormones in Vietnamese
      primiparae.
AB  - OBJECTIVE: Nearly 40 years after Agent Orange was last sprayed, we conducted a
      cross-sectional study to evaluate the impact of dioxin exposure on salivary
      hormones in Vietnamese primiparae. Our previous studies found higher levels of
      salivary cortisol and cortisone in one of the most highly dioxin-contaminated
      areas, known as a "hot-spot", than in a non-exposed area. As a result, we
      suggested that further research with a larger number of participants would be
      needed to confirm whether dioxin affects steroid hormone levels in Vietnamese
      primiparae. METHODS: The concentration of steroid hormones in saliva was
      determined by liquid chromatography (electrospray ionization tandem mass
      spectrometry), whereas the concentrations of polychlorinated dibenzo-p-dioxins
      (PCDDs) and dibenzofurans (PCDFs) in breast milk were determined by gas
      chromatography-high resolution mass spectrometry, for a sample of the population
      from a "hot-spot" (n = 16) and a non-exposed area (n = 10). All subjects were
      aged between 20 and 30 years and had children aged between 4 and 16 weeks.
      RESULTS: The mean toxic equivalence of PCDDs, PCDFs and PCDDs + PCDFs in breast
      milk in the hot-spot area was found to be significantly higher than in the non
      exposed area (p < 0.001). Likewise, salivary cortisol, cortisone and
      dehydroepiandrosterone (DHEA) levels were significantly higher in the hotspot
      area than in the non-exposed area (p < 0.05). As a result, herein we report, for
      the first time, that salivary DHEA levels in primiparae are higher in a hot-spot
      than in a non-exposed area, and that this may be the result of dioxin exposure.
      CONCLUSIONS: Our findings highlight the long-term effects of Agent Orange/dioxin
      on steroid hormones in Vietnamese primiparae in the post-war period.

PMID- 23114997
TI  - The prevalence of primary dystonia: a systematic review and meta-analysis.
AB  - Dystonia is a hyperkinetic movement disorder characterized by sustained muscle
      contractions that produce repetitive movements and abnormal postures. Specific
      information on the prevalence of dystonia has been difficult to establish because
      the existing epidemiological studies of the condition have adopted different
      methodologies for case ascertainment, resulting in widely differing reported
      prevalence. Medline and Embase databases were searched using terms specific to
      dystonia for studies of incidence, prevalence, and epidemiology. All population
      based studies reporting an incidence and/or prevalence of primary dystonia were
      included. Sixteen original studies were included in our systematic review.
      Fifteen studies reported the prevalence of dystonia, including 12 service-based
      and three population-based studies. We performed a meta-analysis on the results
      of the service-based studies, and were able to combine data on the prevalence of
      several dystonia subtypes. From these studies, we calculated an overall
      prevalence of primary dystonia of 16.43 per 100,000 (95% confidence interval
      [CI]: 12.09-22.32). The prevalence of dystonia reported in the three population
      based studies appears higher than that reported in the service-based studies.
      Only 1 of the 16 studies reported an incidence of cervical dystonia. This
      corresponded to a corrected incidence estimate of 1.07 per 100,000 person-years
      (95% CI: 0.86-1.32). Despite numerous studies on the epidemiology of dystonia,
      attempting to determine an accurate prevalence of the condition for health
      services planning remains a significant challenge. Given the methodological
      limitations of the existing studies, our own prevalence estimate of primary
      dystonia likely underestimates the true prevalence of the condition.

PMID- 23114995
TI  - Immune-mediated and autoimmune myocarditis: clinical presentation, diagnosis and
      management.
AB  - According to the current WHO classification of cardiomyopathies, myocarditis is
      an inflammatory disease of the myocardium and is diagnosed by endomyocardial
      biopsy using established histological, immunological and immunohistochemical
      criteria; it may be idiopathic, infectious or autoimmune and may heal or lead to
      dilated cardiomyopathy (DCM). DCM is characterized by dilatation and impaired
      contraction of the left or both ventricles; it may be idiopathic,
      familial/genetic, viral and/or immune. The diagnosis of DCM requires exclusion of
      known, specific causes of heart failure, including coronary artery disease. On
      endomyocardial biopsy, there is myocyte loss, compensatory hypertrophy, fibrous
      tissue and immunohistochemical findings consistent with chronic inflammation
      (myocarditis) in 30-40 % of cases. In a patient subset, myocarditis and DCM
      represent the acute and chronic stages of an inflammatory disease of the
      myocardium, which can be viral, post-infectious immune or primarily organ
      specific autoimmune. Here, we review the clinical presentation, etiopathogenetic
      diagnostic criteria, and management of immune-mediated and autoimmune
      myocarditis. 

PMID- 23114998
TI  - Mineralized poly(lactic acid) scaffolds loading vascular endothelial growth
      factor and the in vivo performance in rat subcutaneous model.
AB  - The functionalization of degradable polymeric scaffolds with therapeutic
      molecules such as vascular endothelial growth factor (VEGF) is a key strategy to
      gain better regenerative ability of damaged bone tissue by stimulating
      vascularization and tissue perfusion. Here, we combined VEGF with poly(lactic
      acid) (PLA) porous scaffold, after modifying the PLA surface with calcium
      phosphate (CaP) mineral. The mineralized PLA scaffold (mPLA) showed more
      effective loading capacity of VEGF than the PLA without mineralization as well as
      profiled sustainable release of VEGF for up to a couple of weeks. The VEGF-loaded
      mPLA scaffold presented significantly improved proliferation of primary
      endothelial cells for up to 7 days, with respect to the scaffold without the VEGF
      loading. The performance of the engineered scaffold was assessed after
      subcutaneous implantation in rats for 4 weeks. Histological results showed
      favorable tissue compatibility of both the mPLA scaffolds (with and without VEGF
      loading), as characterized by infiltration of inflammatory cells, formation of
      fibrous capsule, and ingrowth of fibroblasts into the matrices.
      Immunohistochemical staining of the von Willebrand Factor revealed significantly
      improved formation of neo-capillaries in the VEGF-loaded mPLA. Based on this
      study, the strategy of VEGF loading onto mineralized PLA scaffold is considered
      beneficial for gaining improved vascularization of the polymeric scaffolds,
      suggesting potential applications for bone tissue engineering.

PMID- 23114999
TI  - Dissecting the molecular basis of the contribution of source strength to high
      fructan accumulation in wheat.
AB  - Fructans represent the major component of water soluble carbohydrates (WSCs) in
      the maturing stem of temperate cereals and are an important temporary carbon
      reserve for grain filling. To investigate the importance of source carbon
      availability in fructan accumulation and its molecular basis, we performed
      comparative analyses of WSC components and the expression profiles of genes
      involved in major carbohydrate metabolism and photosynthesis in the flag leaves
      of recombinant inbred lines from wheat cultivars Seri M82 and Babax (SB lines).
      High sucrose levels in the mature flag leaf (source organ) were found to be
      positively associated with WSC and fructan concentrations in both the leaf and
      stem of SB lines in several field trials. Analysis of Affymetrix expression array
      data revealed that high leaf sucrose lines grown in abiotic-stress-prone
      environments had high expression levels of a number of genes in the leaf involved
      in the sucrose synthetic pathway and photosynthesis, such as Calvin cycle genes,
      antioxidant genes involved in chloroplast H(2)O(2) removal and genes involved in
      energy dissipation. The expression of the majority of genes involved in fructan
      and starch synthetic pathways were positively correlated with sucrose levels in
      the leaves of SB lines. The high level of leaf fructans in high leaf sucrose
      lines is likely attributed to the elevated expression levels of fructan synthetic
      enzymes, as the mRNA levels of three fructosyltransferase families were
      consistently correlated with leaf sucrose levels among SB lines. These data
      suggest that high source strength is one of the important genetic factors
      determining high levels of WSC in wheat.

PMID- 23115000
TI  - Identification and analysis of an outer-seed-coat-specific promoter from
      Arabidopsis thaliana.
AB  - Differentiation of the Arabidopsis thaliana (Arabidopsis) seed coat epidermal
      cells involves pronounced changes highlighted by the synthesis and secretion of
      copious amounts of dispensable, pectinaceous mucilage followed by a thick
      cellulosic secondary cell wall. This cell type, therefore, represents an
      excellent molecular-genetic model to study the biosynthesis and modification of
      cell wall components, particularly pectin. To support such research, we sought to
      identify a promoter that drives expression specifically in the Arabidopsis seed
      coat epidermis. Arabidopsis seed coat microarray data was analysed for genes
      expressed in the wild type seed coat but not the seed coat of the apetala2 mutant
      where the epidermal cells fail to differentiate. Of 14 candidate genes, 9 showed
      a seed-specific expression pattern by reverse transcriptase-PCR. Transcriptional
      regulatory region-beta-glucuronidase (GUS) reporter gene fusions introduced into
      Arabidopsis identified one promoter, that of the DIRIGENT PROTEIN1 (DP1) gene, as
      seed coat specific. The specificity of the expression was confirmed using a
      second reporter gene, Citrine YFP. Expression of both reporter genes was limited
      to the epidermal and palisade cell layers of the seed coat. Quantitative PCR data
      using wild type seed coat RNA suggested that the promoter is particularly active
      at 7 days post anthesis. The DP1 promoter was able to direct transcription of GUS
      in a similar pattern in the Brassica napus seed coat. Thus, in addition to its
      application in studying the plant cell wall, this promoter will provide an
      experimental tool for expressing high-valued recombinant proteins as well as
      modifying seed coat traits in economically important crops.

PMID- 23115001
TI  - Posterior ventricular septal perforation: sandwich technique via right
      ventriculotomy using BioGlue.
AB  - We present a case in which the sandwich technique was successfully applied via
      right ventriculotomy for posterior infarction ventricular septal perforation 2
      days after acute posterior myocardial infarction in a 73-year-old male patient.
      The sealant BioGlue was applied to the space between the two patches instead of
      gelatin-resorcinol-formaldehyde biological glue. The postoperative course was
      good, and the patient was discharged on day 24 after surgery with no recognized
      residual shunt.

PMID- 23115002
TI  - Results of cardiac surgery in advanced liver cirrhosis.
AB  - PURPOSE: Cardiac surgery for the patients with advanced liver cirrhosis is still
      challenging. High mortality has been reported in the literature. We evaluate the
      clinical outcome of cardiac surgery in patients with advanced liver cirrhosis.
      METHODS: Patients with advanced liver cirrhosis who underwent cardiac surgery
      between October 1999 and April 2009 were reviewed. The severity of liver
      cirrhosis was assessed using Child-Pugh class, Child-Pugh score, and MELD score.
      Advanced liver cirrhosis was defined as Child-Pugh class B or C. Cardiopulmonary
      bypass (CPB) was carried out at higher flow rate (2.4-3.2 L/min/m(2)), and
      hematocrit (25-30 %). Moderate and more tricuspid regurgitation were aggressively
      treated. Dilutional ultrafiltration was performed at the termination of CPB.
      RESULTS: Eighteen patients (mean age 70 years, male:female = 14:4) were
      identified. Twelve patients had hepatitis virus infection and 6 cases were
      alcohol-related. Fourteen patients were graded as Child-Pugh class B and 4 in
      class C. Seventeen patients underwent cardiac surgery with the use of
      cardiopulmonary bypass, and 1 patient underwent off-pump coronary artery bypass
      surgery. The overall mortality rate was 17 % (3 of 18). The cause of death was
      liver failure, esophageal variceal bleeding and bacteremia. The mortality of redo
      surgery was high (50 %). The incidence of postoperative liver failure was 11 % (2
      of 18). Child-Pugh class or score was not correlated with hospital mortality.
      MELD score was significantly higher in hospital mortality (10.8 +/- 4.0 vs. 17.3
      +/- 2.1, p = 0.001). CONCLUSIONS: Although the mortality of redo surgery was
      high, cardiac surgery could be safely performed in selected patients with
      advanced liver cirrhosis.

PMID- 23115003
TI  - Valve replacement via upper partial sternotomy for quadricuspid aortic valve.
AB  - A 52-year-old man was referred to our clinic because of chronic heart failure. A
      Levine 3/6 diastolic heart murmur was audible at the apex. Chest radiography
      showed an enlarged left ventricle. Transthoracic echocardiography showed
      moderately severe aortic regurgitation. Left ventricular end-diastolic/systolic
      diameter and ejection fraction were 75/59 mm and 41 %, respectively. Preoperative
      transesophageal 3-dimensional echocardiography revealed a quadricuspid aortic
      valve whose cusps were of almost equal size. Aortic valve replacement was
      performed via upper partial sternotomy.

PMID- 23115004
TI  - Outcomes after adjuvant platinum-based chemotherapy in elderly NSCLC patients
      with T4 disease.
AB  - BACKGROUND: The postoperative management of elderly patients with T4, N0-1, M0
      non-small cell lung cancer (NSCLC) remains controversial. The objective of this
      study was to evaluate the association of adjuvant chemotherapy with survival and
      toxicity among these patients. METHODS: Using surveillance, epidemiology and end
      results registry data linked to Medicare claims, we identified 389 elderly
      patients with resected T4, N0-1, M0 NSCLC diagnosed between 1992 and 2007. We
      compared survival of patients treated with and without platinum-based
      chemotherapy using a Cox regression adjusting for propensity scores for
      chemotherapy use and use of radiotherapy. We used logistic regression to assess
      the risk of adverse events in patients receiving chemotherapy. RESULTS: No
      benefit was noted in overall survival with adjuvant chemotherapy after PS
      adjustment for both N0 (hazard ratio 0.78, 95% confidence interval 0.50-1.23) and
      N1 (hazard ratio 1.01, 95% confidence interval 0.67-1.53) cancers. Patients
      receiving adjuvant chemotherapy experienced severe adverse events more frequently
      than patients who did not receive chemotherapy. CONCLUSIONS: Use of adjuvant
      chemotherapy in elderly patients with T4, N0-1, M0 NSCLC was not associated with
      a survival advantage and was associated with higher rates of severe toxicity.

PMID- 23115005
TI  - Synergistic effect of Bcl-2 and cyclin A2 on adverse recurrence-free survival in
      stage I non-small cell lung cancer.
AB  - BACKGROUND: The prognostic significance of cyclin A2 overexpression in non-small
      cell lung cancer (NSCLC) is controversial. METHODS: To understand the effect of
      cyclin A2 on recurrence in NSCLC, we retrospectively analyzed the expression of
      Bcl-2, cyclin A2, E-cadherin, Ki-67, and p53 using immunohistochemistry in 635
      NSCLCs. RESULTS: Overexpression of cyclin A2 was found in 466 (73%) of 635
      NSCLCs, and recurrence occurred in 291 (46%) of 635 NSCLCs with a median follow
      up of 5.4 years. The relationship between recurrence and cyclin A2 overexpression
      was not homogenous by pathologic stage (Breslow-Day test for homogeneity, P =
      0.007). Overexpression of cyclin A2 was associated with poor recurrence-free
      survival (RFS) in 374 stage I NSCLCs (P = 0.02), and RFS was worse in patient
      with negative expression of Bcl-2 than those with positive expression of Bcl-2.
      Cox proportional hazard analysis showed that stage I NSCLC patients with
      overexpression of cyclin A2 and negative expression of Bcl-2 had poorer RFS
      (hazard ratio = 3.86, 95% confidence interval = 1.07-15.77; P = 0.03) than those
      with normal expression of cyclin A2 and Bcl-2, after adjusting for age, adjuvant
      radiotherapy, and histology. Neural network and generalized linear model
      including cyclin A2 and Bcl-2 showed best performance in the prediction of
      recurrence; error rates for neural network and generalized linear model were 15%
      and 12%, respectively. CONCLUSIONS: Negative effect of cyclin A2 on RFS in stage
      I NSCLC was aggravated by negative expression of Bcl-2.

PMID- 23115006
TI  - Colorectal liver metastases: state of the art imaging.
AB  - Colorectal cancer is a leading cause of death with mortality determined
      predominately by metastatic involvement of the liver. Treatment of liver
      metastases continues to evolve and imaging plays an essential role in initial
      staging, preoperative planning, and treatment monitoring. This review article
      discusses the current role of imaging in the management of patients with
      colorectal liver metastases. Particular challenges such as hepatic steatosis,
      disappearing metastases, and following treated lesions are addressed.

PMID- 23115007
TI  - Diagnostic and prognostic relevance of MMP-11 expression in the stromal
      fibroblast-like cells adjacent to invasive ductal carcinoma of the breast.
AB  - BACKGROUND: Matrix metalloproteinase 11 (MMP-11) is a matrix degrading enzyme
      known to be involved in the remodeling of extracellular matrix proteins. This
      enzyme recently has been reported to play a key role in tumor progression and
      results in poor clinical outcomes for several different types of tumors. METHODS:
      A total of 192 patients diagnosed with invasive ductal carcinoma between 2000 and
      2005 were included in this study. MMP-11 expression in tumors and stromal
      fibroblast-like cells was analyzed by immunohistochemical staining on a tissue
      microarray. Subsequently, evaluation of the associations between MMP-11
      expression and clinicopathological characteristics was performed. RESULTS: MMP-11
      expression of stromal fibroblast-like cells was correlated with prognostic
      factors, including tumor size, metastasis, histological grade, central tumor
      fibrosis, p53 expression, and luminal A subtype and was linked to therapeutic
      markers, such as ER and HER2 (all p < 0.05). There was a significant relationship
      between worse overall survival and MMP-11 expression in both tumors and stromal
      fibroblast-like cells (all p < 0.05). In multivariate analysis, MMP-11 expression
      of stromal fibroblast-like cells was still significantly associated with poor
      prognosis (p = 0.043). CONCLUSIONS: MMP-11 expression was significantly related
      to clinicopathological parameters, which may be essential to the prediction of
      disease outcome in patients with invasive ductal carcinoma of the breast.

PMID- 23115009
TI  - PPARalpha activation in portal hypertension.

PMID- 23115008
TI  - O-Mannosylation and human disease.
AB  - Glycosylation of proteins is arguably the most prevalent co- and post
      translational modification. It is responsible for increased heterogeneity and
      functional diversity of proteins. Here we discuss the importance of one type of
      glycosylation, specifically O-mannosylation and its relationship to a number of
      human diseases. The most widely studied O-mannose modified protein is alpha
      dystroglycan (alpha-DG). Recent studies have focused intensely on alpha-DG due to
      the severity of diseases associated with its improper glycosylation. O
      mannosylation of alpha-DG is involved in cancer metastasis, arenavirus entry, and
      multiple forms of congenital muscular dystrophy [1, 2]. In this review, we
      discuss the structural and functional characteristics of O-mannose-initiated
      glycan structures on alpha-DG, enzymes involved in the O-mannosylation pathway,
      and the diseases that are a direct result of disruptions within this pathway. 

PMID- 23115011
TI  - HCC Is promoted by bacterial translocation and TLR-4 signaling: a new paradigm
      for chemoprevention and management.

PMID- 23115010
TI  - Cholesterol and nonalcoholic fatty liver disease: renewed focus on an old
      villain.

PMID- 23115012
TI  - Reply:.

PMID- 23115013
TI  - Recombinant anti-podoplanin (NZ-1) immunotoxin for the treatment of malignant
      brain tumors.
AB  - Our study demonstrates the glioma tumor antigen podoplanin to be present at very
      high levels (>90%) in both glioblastoma (D2159MG, D08-0308MG and D08-0493MG) and
      medulloblastoma (D283MED, D425MED and DAOY) xenografts and cell line. We
      constructed a novel recombinant single-chain antibody variable region fragment
      (scFv), NZ-1, specific for podoplanin from the NZ-1 hybridoma. NZ-1-scFv was then
      fused to Pseudomonas exotoxin A, carrying a C-terminal KDEL peptide (NZ-1
      PE38KDEL). The immunotoxin (IT) was further stabilized by a disulfide (ds) bond
      between the heavy-chain and light-chain variable regions as the construct NZ-1
      (scdsFv)-PE38KDEL. NZ-1-(scdsFv)-PE38KDEL exhibited significant reactivity to
      glioblastoma and medulloblastoma cells. The affinity of NZ-1-(scdsFv), NZ-1
      (scdsFv)-PE38KDEL and NZ-1 antibody for podoplanin peptide was 2.1 * 10(-8) M,
      8.0 * 10(-8) M and 3.9 * 10(-10) M, respectively. In a protein stability assay,
      NZ-1-(scdsFv)-PE38KDEL retained 33-98% of its activity, whereas that of NZ-1
      PE38KDEL declined to 13% of its initial levels after incubation at 37 degrees C
      for 3 days. In vitro cytotoxicity of the NZ-1-(scdsFv)-PE38KDEL was measured in
      cells isolated from glioblastoma xenografts, D2159MG, D08-0308MG and D08-0493MG,
      and in the medulloblastoma D283MED, D425MED and DOAY xenografts and cell line.
      The NZ-1-(scdsFv)-PE38KDEL IT was highly cytotoxic, with an 50% inhibitory
      concentration in the range of 1.6-29 ng/ml. Significantly, NZ-1-(scdsFv)-PE38KDEL
      demonstrated tumor growth delay, averaging 24 days (p < 0.001) and 21 days (p <
      0.001) in D2159MG and D283MED in vivo tumor models, respectively. Crucially, in
      the D425MED intracranial tumor model, NZ-1-(scdsFv)-PE38KDEL caused a 41%
      increase in survival (p <= 0.001). In preclinical studies, NZ-1-(scdsFv)-PE38KDEL
      exhibited significant potential as a targeting agent for malignant brain tumors.

PMID- 23115014
TI  - Explaining freezing of gait in Parkinson's disease: motor and cognitive
      determinants.
AB  - Freezing of gait (FOG) is part of a complex clinical picture in Parkinson's
      disease (PD) and is largely refractory to standard care. Diverging hypotheses
      exist about its origins, but a consolidated view on what determines FOG is
      lacking. The aim of this study was to develop an integrative model of FOG in
      people with PD. This cross-sectional study included 51 Parkinson subjects: 24
      patients without FOG and 27 with FOG matched for age, gender, and disease
      severity. Subjects underwent an extensive clinical test battery evaluating
      general disease characteristics, gait and balance, nongait freezing, and
      cognitive functions. The relative contribution of these outcomes to FOG was
      determined using logistic regression analysis. The combination of the following
      four independent contributors provided the best explanatory model of FOG (R(2) =
      0.49): nongait freezing; levodopa equivalent dose (LED); cognitive impairment;
      and falls and balance problems. The model yields a high-risk profile for FOG (P >
      95%) when Parkinson patients are affected by at least one type of nongait
      freezing (e.g., freezing of other repetitive movements), falls or balance
      problems during the last 3 months, and a Scales for Outcomes in Parkinson's
      Disease-Cognition score below 28. A high LED further increases the risk of FOG to
      99%. Nongait freezing, increased dopaminergic drug dose, cognitive deficits, and
      falls and balance problems are independent determinants of FOG in people with PD
      and may play a synergistic role in its manifestation.

PMID- 23115015
TI  - Effect of progesterone receptor status on maspin synthesis via nitric oxide
      production in neutrophils in human breast cancer.
AB  - BACKGROUND: Although progesterone receptor (PR) status, similarly to estrogen
      receptor status, is of prognostic importance in breast cancer, the involvement of
      the PR in breast cancer remains obscure. Studies were conducted to determine the
      function of the PR in neutrophils in the nitric oxide-induced synthesis of
      maspin, an anti-breast-cancer protein produced in nonmalignant mammary cells and
      in neutrophils in the circulation. METHODS: PR status was determined by
      immunohistochemistry. Maspin synthesis was determined by in-vitro translation of
      messenger RNA and quantified by enzyme-linked immunosorbent assay. Nitric oxide
      was determined by the methemoglobin method. RESULTS: It was found that PR status
      in neutrophils was identical with that in malignant breast tissues. A Scatchard
      plot for progesterone binding to normal and PR-positive (PR+) neutrophils
      revealed that whereas normal neutrophils had 11.5 * 10(10) PR sites/cell with K d
      = 47.619 nM, PR+ neutrophils had 6.6 * 10(10) PR sites/cell with K d = 47.619 nM.
      The progesterone negative (PR-) neutrophils failed to bind to progesterone.
      Incubation of normal and PR+ neutrophils with 25 nM progesterone produced 1.317
      MUM NO and 2.329 nM maspin; the PR+ neutrophils produced 0.72 MUM NO and 1.138 nM
      maspin. The PR- neutrophils failed to produce any NO or maspin in the presence of
      progesterone. Inhibition of progesterone-induced NO synthesis led to complete
      inhibition of maspin synthesis in all neutrophils. CONCLUSION: These results
      suggest that estrogen and progesterone complement each other in NO-induced maspin
      synthesis, and do not necessarily antagonize in the synthesis of the anti-breast
      cancer protein.

PMID- 23115016
TI  - Procedures for location of non-palpable breast lesions: a systematic review for
      the radiologist.
AB  - Accurate location of small breast lesions is mandatory for proper surgical
      management. The purpose of this article is systematically review procedures used
      to locate non-palpable breast lesions, including a description of the current
      status, advantages, and disadvantages for each technique. A total of 47 articles
      were finally included: 7 articles for the wire location technique, 5 articles for
      the radioguided location technique, 13 articles that compare wire location with
      radioguided location, 3 articles for the carbon location technique, 2 articles
      that compare wire location with carbon location, and 17 articles for the clip
      location technique. The success of location and the clear margin are reported for
      each location technique and for the separate articles included; clip migration
      shift, also, is reported for the clip location technique. Odds ratio with related
      95 % confidence intervals were also calculated for successful location.
      Comparative analysis or meta-analysis for all the different breast lesion
      location techniques is missing. Prospective investigations and randomized
      investigations for homogeneous populations are still needed to determine which is
      the most cost-effective modality among those used to date. 

PMID- 23115017
TI  - Isolation of antithrombotic phenolic compounds from the leaves of Crataegus
      pinnatifida.
AB  - Four novel phenolic compounds (1-4) were isolated from the leaves of Crataegus
      pinnatifida, along with three known ones (5-7). Their structures were elucidated
      as: methyl 4-O-beta-D-glucopyranosyl-3-[(2E,6E)-8-O-beta-D-glucopyranosyl-3,7
      dimethyl-2,6-octadienyl] benzoate (1), biphenyl-5-ol-3-O-beta-D-glucoside (2),
      3,4'-dimethoxy-biphenyl-5-ol-4-O-beta-D-glucoside (3), (E)-6-(benzoyloxy)-1
      hydroxyhex-3-en-2-O-beta-D-glucoside (4), shanyenoside A (5), eriodectyol (6),
      and 2"-O-rhamnosyl vitexin (7), using a combination of mass spectroscopy, 1D and
      2D NMR spectroscopy, and chemical analysis. The antithrombotic activity of the
      isolated compounds was investigated on the transgenic zebra fish system. Among
      them, eriodectyol (6) potently inhibited the production of thrombus.

PMID- 23115018
TI  - Antibiofilm activity of Dendrophthoe falcata against different bacterial
      pathogens.
AB  - Dendrophthoe falcata is a hemiparasitic plant commonly used for ailments such as
      ulcers, asthma, impotence, paralysis, skin diseases, menstrual troubles,
      pulmonary tuberculosis, and wounds. In this context, the validations of the
      traditional claim that the leaf extract of D. falcata possesses antibiofilm and
      anti-quorum sensing activity against different bacterial pathogens were assessed.
      The bacterial biofilms were quantified by crystal violet staining. Among the 17
      bacterial pathogens screened, the methanolic fraction of the leaf extract clearly
      demonstrated antibiofilm activity for Proteus mirabilis, Vibrio vulnificus,
      Aeromonas hydrophila, Shigella sonnei, Chromobacterium violaceum ATCC 12472,
      Vibrio parahaemolyticus, Vibrio harveyi, Vibrio alginolyticus, Vibrio cholerae,
      and Proteus vulgaris. At biofilm inhibitory concentrations, biofilm formation was
      reduced by up to 70-90 %. Furthermore, the potential quorum-sensing activity of
      the leaf extract was tested by agar well diffusion using Chromobacterium
      violaceum (ATCC 12472 & CV O26) reporter strains. The inhibition of violacein
      production may be due to direct or indirect interference on QS by active
      constituents or the interactive effect of different phytocompounds present in the
      extracts. This is the first report on antibiofilm and QS activity of D. falcata
      leaf extracts, signifying the scope for development of complementary medicine for
      biofilm-associated infections.

PMID- 23115019
TI  - In vitro anti-inflammatory effects of beta-carboline alkaloids, isolated from
      Picrasma quassioides, through inhibition of the iNOS pathway.
AB  - In our previous study, fourty-eight compounds have been isolated and identified
      from the roots of Picrasma quassioides, which have been widely used as a
      traditional Chinese medicine for clearing heat and for detoxification as
      described in the Chinese Pharmacopoeia. beta-Carboline alkaloids are commonly
      considered as main active constituents of P. quassioides, but the molecular
      mechanism remains yet unknown. In the present paper, one new beta-carboline
      alkaloid together with two known beta-carboline alkaloids have been investigated
      for their anti-inflammatory effect and mechanism of action in cultured macrophage
      RAW 264.7 cells. Griess assay was used to evaluate the inhibitory effect on the
      overproduction of nitric oxide. ELISA was used to determine the level of
      proinflammatory cytokines including TNF-alpha and IL-6. The inhibitory effect on
      the enzymatic activity of COX-2 and inducible nitric oxide synthase were tested
      by colorimetric and fluorimetric methods, respectively. Western blot was used to
      detect the expression of inducible nitric oxide synthase and COX-2. All three
      beta-carboline alkaloids suppressed LPS-stimulated nitric oxide production and
      proinflammatory cytokines secretion, including TNF-alpha and IL-6 in a dose
      dependent manner. They also strongly inhibited the expression of inducible nitric
      oxide synthase and inducible nitric oxide synthase enzymatic activity, whereas
      the expression of COX-2 and COX-2 enzymatic activity were not affected. These
      results indicated that potent inhibition of nitric oxide, TNF-alpha, and IL-6,
      but not COX-2 expression and COX-2 activity, might constitute the anti
      inflammatory mechanism of beta-carboline alkaloids. beta-Carboline alkaloids
      suppressed the overproduction of nitric oxide through downregulation of inducible
      nitric oxide synthase expression and inducible nitric oxide synthase enzymatic
      activity in an LPS-stimulated macrophage.

PMID- 23115020
TI  - Short-term in vitro responses of human peripheral blood monocytes to ferritic
      stainless steel fiber networks.
AB  - Beneficial effects on bone-implant bonding may accrue from ferromagnetic fiber
      networks on implants which can deform in vivo inducing controlled levels of
      mechanical strain directly in growing bone. This approach requires ferromagnetic
      fibers that can be implanted in vivo without stimulating undue inflammatory cell
      responses or cytotoxicity. This study examines the short-term in vitro responses,
      including attachment, viability, and inflammatory stimulation, of human
      peripheral blood monocytes to 444 ferritic stainless steel fiber networks. Two
      types of 444 networks, differing in fiber cross section and thus surface area,
      were considered alongside austenitic stainless steel fiber networks, made of
      316L, a widely established implant material. Similar high percent seeding
      efficiencies were measured by CyQuant(r) on all fiber networks after 48 h of cell
      culture. Extensive cell attachment was confirmed by fluorescence and scanning
      electron microscopy, which showed round monocytes attached at various depths into
      the fiber networks. Medium concentrations of lactate dehydrogenase (LDH) and
      tumor necrosis factor alpha (TNF-alpha) were determined as indicators of
      viability and inflammatory responses, respectively. Percent LDH concentrations
      were similar for both 444 fiber networks at all time points, whereas
      significantly lower than those of 316L control networks at 24 h. All networks
      elicited low-level secretions of TNF-alpha, which were significantly lower than
      that of the positive control wells containing zymosan. Collectively, the results
      indicate that 444 networks produce comparable responses to medical implant grade
      316L networks and are able to support human peripheral blood monocytes in short
      term in vitro cultures without inducing significant inflammatory or cytotoxic
      effects.

PMID- 23115021
TI  - Comparison of dysphagia before and after deep brain stimulation in Parkinson's
      disease.
AB  - Although dysphagia is a common problem for many Parkinson's disease (PD)
      patients, the effect of deep brain stimulation (DBS) on swallowing is unclear.
      Fourteen subjects with advanced PD underwent videofluorographic swallowing
      studies prior to bilateral DBS of the subthalamic nucleus (STN) and at 3 and 12
      months postprocedure. They were tested under several stimulation and medication
      conditions. Subjects completed the Dysphagia Handicap Index at each time. There
      was a strong trend toward improved swallowing response for solid intake in the
      medication-free condition with the stimulator on compared with the stimulator off
      (P = .0107). Also, there was a trend toward improved oral preparation of thin
      liquids (P = .0368) in the medication-free condition when the stimulator was on
      versus off 12 months later. The remaining swallowing parameters showed no change
      or worsening of swallowing function regardless of stimulator or medication
      status. Results of the Dysphagia Handicap Index revealed significant improvement
      in subject self-perception of swallowing 3 and 12 months following the procedure
      compared with baseline on the functional subscale (P = .020 and P = .010,
      respectively), the emotional subscale (P = .013 and P = .003, respectively), and
      the total score (P = .025 and P = .003, respectively). These data suggest that
      bilateral STN-DBS does not substantively impair swallowing in PD. In addition, it
      may improve motor sequencing of the oropharyngeal swallow for solid consistencies
      (which are known to provide increased sensory feedback to assist motor planning
      of the oropharyngeal swallow). Subjects with advanced PD who are undergoing DBS
      may perceive significant improvement in swallowing ability despite the lack of
      objective improvements in swallowing function.

PMID- 23115022
TI  - Establishing a general practitioner led minor injury service: mixed methods
      evaluation at 10 months with an emphasis on use of radiology by GPs in the out-of
      hours setting.
AB  - AIMS AND METHODS: A mixed methods study was conducted to evaluate a recently
      established general practitioner (GP) led minor injury (MI) service; it included
      a patient feedback study, a qualitative enquiry into the experience of the MI
      GPs, and analysis of use of radiology. RESULTS: Forty-nine (81.6 %) patients
      surveyed were seen in 30 min or less. Forty-five (75 %) felt that the quality of
      the service was excellent/very good. Twenty-seven (45 %) responders felt that the
      X-ray service was expensive; 49 (81.6 %) patients said that they would be happy
      to use the service again. 271 X-rays were taken (137, 50.55 % upper limb, 95,
      35.06 % lower limb, 18, 6.64 % CXR). One hundred and ninety-four (73.48 %)
      patients were self-financing. There was an 86.72 % (235/271) concordance between
      GP/radiologist findings. Issues elaborated by MI GPs at the focus group included
      secondary care/hospital interaction, patients' experience, professional
      fulfilment, competence concerns, finances, and interest in educational resources;
      they were unanimous in maintaining the service at 10 months. CONCLUSIONS: This
      study demonstrates a positive experience by patients, and conservative evaluation
      of X-rays by GPs.

PMID- 23115023
TI  - Warfarin and topical miconazole: the potential for a clinically significant
      interaction.

PMID- 23115024
TI  - Differential effects of low- and high-dose GW2974, a dual epidermal growth factor
      receptor and HER2 kinase inhibitor, on glioblastoma multiforme invasion.
AB  - Aberrant expression of epidermal growth factor receptor (EGFR; ErbB1) and HER2
      (ErbB2) tyrosine kinases frequently occurs in glioblastoma multiforme (GBM)
      patients and is considered to be associated with tumor malignancy and poor
      patient prognosis. In the present study, a dual EGFR and HER2 inhibitor (GW2974)
      was evaluated for its effects in GBM in vitro and in vivo. Results showed that
      low-concentration GW2974 inhibited GBM cell invasion, whereas a high
      concentration of the same compound counteracted this effect. Similar results were
      observed in an intracranial GBM xenograft model, in which, although both doses of
      GW2974 slowed tumor growth, no improvement in survival was observed in mice
      treated with high-dose GW2974, presumably because of the augmentation of tumor
      invasion. By protein microarray and Western blot analyses, the p38 mitogen
      activated protein kinase (MAPK) pathway was found to be activated in GBM cells
      under high-concentration GW2974. Additionally, blockage of the p38 MAPK pathway
      reproduced the inhibitory effect of low-concentration GW2974 on cell invasion.
      These data suggest that the p38 MAPK pathway might contribute to the differential
      regulation of cell invasion by GW2974. Taken together, our results indicate that
      GW2974 exerts different effects in GBM depending on drug dosage. This offers a
      new perspective on the role of GW2974 in tumor progression, providing a potential
      strategy for GBM treatment based on precise prescription.

PMID- 23115025
TI  - Interaction between Treg cells and angiogenesis: a dark double track.

PMID- 23115026
TI  - Applying bioinformatics to proteomics: is machine learning the answer to
      biomarker discovery for PD and MSA?
AB  - Bioinformatics tools are increasingly being applied to proteomic data to
      facilitate the identification of biomarkers and classification of patients. In
      the June, 2012 issue, Ishigami et al. used principal component analysis (PCA) to
      extract features and support vector machine (SVM) to differentiate and classify
      cerebrospinal fluid (CSF) samples from two small cohorts of patients diagnosed
      with either Parkinson's disease (PD) or multiple system atrophy (MSA) based on
      differences in the patterns of peaks generated with matrix-assisted
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). PCA
      accurately segregated patients with PD and MSA from controls when the cohorts
      were combined, but did not perform well when segregating PD from MSA. On the
      other hand, SVM, a machine learning classification model, correctly classified
      the samples from patients with early PD or MSA, and the peak at m/z 6250 was
      identified as a strong contributor to the ability of SVM to distinguish the
      proteomic profiles of either cohort when trained on one cohort. This study, while
      preliminary, provides promising results for the application of bioinformatics
      tools to proteomic data, an approach that may eventually facilitate the ability
      of clinicians to differentiate and diagnose closely related parkinsonian
      disorders.

PMID- 23115027
TI  - [Evidence-based medicine in surgical practice - locating clinical studies and
      systematic reviews by searching the Medline database].
AB  - BACKGROUND: Every day approximately 75 clinical trials and 11 systematic reviews
      are published in the health-care intervention and medical field. Due to this
      growing number of publications it is a challenge for every practicing clinician
      to keep track with the latest research. The implementation of new and effective
      diagnostic and therapeutic interventions into daily clinical routine may thus be
      delayed. Conversely, ineffective or even harmful interventions might still be in
      use. Decision-making in evidence-based medicine (EBM) requires consideration of
      the most recent high quality evidence. Randomised controlled trials (RCTs) are
      regarded as the "gold standard" to prove the efficacy of surgical interventions
      in patient-oriented research. Systematic reviews combine results from RCTs by
      summarising single RCTs which answer a particular clinical question. Some basic
      knowledge in systematic literature searching is required and helpful for
      detecting relevant publications. MATERIAL AND METHODS: This article shows various
      possibilities for locating clinical studies and systematic reviews in the
      database Medline on the basis of illustrative step-by-step instructions. RESULTS
      AND CONCLUSION. Depending on the aim and topic of the literature search, the time
      required for the task may vary. In routine practice, a systematic literature
      search is unrealistic in most cases. Clinicians in need of a quick update of
      current evidence on a certain clinical topic may make use of up-to-date
      systematic reviews. During a systematic literature search, different approaches
      and strategies might be necessary.

PMID- 23115028
TI  - [Principles of surgery for retroperitoneal sarcoma].
AB  - The successful treatment of retroperitoneal soft tissue sarcomas requires an
      experienced team consisting of not only surgeons but also pathologists and
      radiologists with a high case load in these tumours. The decisive step in the
      preoperative work-up of these, often late detected, tumours is their reliable
      grading as well as, if necessary, recognition of the sarcoma subtype as a basis
      for determining the direction of treatment. Imaging methods provide essential
      information with regard to the detection of infiltration of neighbouring
      structures and organs. Magnetic resonance imaging (MRI) is the most suitable
      method for this purpose. Punch needle biopsy is to be preferred over fine-needle
      biopsy in all cases for histological confirmation. The surgical standard
      procedure for the majority of the patients comprises multivisceral resection as
      principle, with additional colon resection, nephrectomy, and resection of
      abdominal wall musculature or, respectively, the psoas muscle in order to achieve
      an R0 resection of the retroperitoneal compartment. If only small margins of
      clearance are to be expected, a preoperative (neoadjuvant) treatment with
      radiation and/or chemotherapy even in combination with deep wave hyperthermia for
      high grade sarcomas should be strongly considered. Adjuvant postoperative
      radiation therapy often cannot be adequately applied due to the occupation of the
      former tumour bed by abdominal organs that were displaced by the mass effect,
      especially the radiation-sensitive small bowel. The optimal treatment strategy
      for these patients must be discussed in a multidisciplinary tumour board prior to
      any diagnostic or therapeutic procedure. 

PMID- 23115029
TI  - [The development process of colon cancer centres].
AB  - Colon carcinomas are the most common malignant tumours in the Western world.
      Important findings about the overall quality of medical care have been reported
      in multi-centre observational studies. A quality enhancement of therapeutic care
      can be achieved by an additional increase in diagnostic and therapeutic measures
      in the interdisciplinary setting. The development of colon cancer centres
      improves the chance to objectively observe the results of medical care induced by
      the development of an interdisciplinary and cross-sectoral unit that includes a
      comprehensive medical care for patients. The implementation of the current
      medical findings based on evidence in clinical routine, the inspection of the
      usage of guidelines by external specialists as part of an audit and the
      continuous correction of analysed deficits in the course of treatment guarantee a
      continuous improvement of service.

PMID- 23115030
TI  - [Acute scrotum in childhood].
AB  - BACKGROUND: Due to the variety of differential diagnoses causing acute scrotum
      and their possible consequences, this finding is a challenge for diagnostic and
      therapeutic management in the daily clinical practice of paediatric medicine.
      PATIENTS AND METHODS: Through a defined time period, all consecutive paediatric
      patients of a tertiary surgical centre aged up to 16 years who were diagnosed
      with and treated for primary acute scrotum were prospectively registered and
      retrospectively evaluated for patient, finding and treatment (intervention)
      associated specifics in this systematic unicentric observational study (design:
      case series) to reflect daily clinical practice. RESULTS: A total of 141 cases
      with acute scrotum were enrolled in the study during the 10-year period from
      January 2000 to December 2009. Eight percent of cases (n = 11) showed bilateral
      findings. There were two age peaks: newborns and puberty. The most common
      diagnoses were epididymitis and orchitis (26 %), torsion of the testicular
      appendix (22 %) and testicular torsion (21 %). Trauma, hydrocele, inguinal
      hernia, idiopathic scrotal oedema and tumours were rather rare differential
      diagnoses as possible causes for an acute scrotum. The mean period of discomfort,
      complaints and symptoms up to presenting in the outpatient clinic was 24 hours.
      For sixty percent (n = 84, i.e., all patients treated conservatively and 43 % of
      the operated patients) an imaging study was obtained with ultrasound or Doppler
      ultrasonography, respectively. Two thirds of the patients underwent an operative
      exploration. The orchiectomy rate in testicular torsion amounted to 40 %. In one
      newborn, a bilateral orchiectomy was necessary. In patients with unilateral
      orchiectomy, a prophylactic fixation of the contralateral testis was performed
      preferentially at 4-8 weeks after the initial intervention even though a
      simultaneous procedure is being increasingly used. CONCLUSIONS: In approximately
      one fifth of registered patients, a testicular torsion is present causing the
      acute scrotum, and leading to an obligatory surgical intervention. Various
      causative differential diagnoses can be clarified by precise medical history and
      exact physical examination. Imaging procedures can be helpful in decision
      finding. Finally, the clinical finding is crucial and decisive. If a testicular
      torsion cannot reliably be excluded by clinical investigation or imaging, an
      immediate surgical exploration of the testis has to be performed.

PMID- 23115031
TI  - [Results of surgical treatment of hiatal hernia].
AB  - BACKGROUND: Hiatus hernias are considered as the most prominent form of
      diaphragmatic hernias. The passage is defined through the oesophageal hiatus,
      resulting in a superdiaphragmatic displacement of parts of the stomach or the
      complete stomach, respectively. In our work we investigated the treatment of
      partial thoracic stomach with both open and minimally invasive surgical
      procedures emphasising the view on operating data, the success of the surgery and
      recurrence rates. Patients with mesh insertion for hernia defect closures were
      considered separately. MATERIAL AND METHOD: 94 Patients were treated in the
      period from 01.01.2003 to 01.06.2010. The ratio male/female was 2 : 1. The median
      age was 66 years. All data were prospectively collected by means of surgical
      protocols and data from the central patient records and analysed retrospectively.
      The statistical analyses were performed with SPSS 18.0 (SPSS Inc., Chicago, IL,
      USA). Any existing significances were determined using the T-test. RESULTS: Of
      the 94 patients, 65 were operated laparoscopically. In the case of nine patients
      an initial laparoscopic surgery had to be changed to an open procedure. The
      reasons for switching surgical procedures were splenic bleeding in the case of 2
      patients, intestinal injury due to perforation by the trocar in one case and
      unclear surgical situs in 6 cases. The postoperative complication rate was 24 %.
      The main reasons were a delayed achievement of passage. The mortality rate was 0
      %. The comparison between laparoscopic and open groups showed, by comparable
      complication and recurrence rates, a shorter recovery time in favour of patients
      operated on laparoscopically. Additionally it can be stated that a bridge closure
      with mesh (ePTFE) had no significant influence on the postoperative outcome.
      Therefore we cannot confirm the postulated poor postoperative results of other
      groups. CONCLUSION: In summary, the clear trend in the surgical treatment of
      hiatus hernias is to minimally invasive surgery. Only for patients with multiple
      previous operations, who are expected to have strong adhesions, the operation
      with comparable morbidity and mortality rates can also be planned primarily as
      open. In this case, however, longer postoperative recovery times must be
      expected. Large defects can be treated with comparable complication and
      recurrence rates by mesh insertion (ePTFE).

PMID- 23115032
TI  - Percutaneous left ventricular partitioning device for chronic heart failure.
AB  - We report the first implantation of a percutaneous left ventricular partitioning
      device in the Netherlands. This device is developed for patients with chronic
      heart failure due to a left ventricular apical aneurysm caused by an anterior
      myocardial infarction.

PMID- 23115033
TI  - Increasing irradiation temperature maximizes vitamin E grafting and wear
      resistance of ultrahigh molecular weight polyethylene.
AB  - Vitamin E stabilization of radiation crosslinked ultrahigh molecular weight
      polyethylene (UHMWPE) for total joint implants can be done by blending of UHMWPE
      resin powder with vitamin E, followed by consolidation and irradiation of the
      blend. It is well known that vitamin E prevents crosslinking in UHMWPE during
      ionizing radiation. We hypothesized that there would also be a significant amount
      of grafting of vitamin E onto UHMWPE during irradiation. Spectroscopic analysis
      of radiation crosslinked vitamin E-blended UHMWPE before and after extraction
      with boiling hexane showed vitamin E grafting in up to 30% of the blended vitamin
      E. Grafting increased with irradiation temperature. We also discovered that
      increasing irradiation temperature resulted in better preservation of active
      vitamin E in the polymer and increased crosslinking efficiency of UHMWPE. As a
      result, warm-irradiated vitamin E-blended UHMWPEs had significantly less wear
      than those irradiated at ambient temperature. It may be desirable to graft
      vitamin E on UHMWPE to decrease the possibility of elution and increase long-term
      stability. Warm irradiation of vitamin E blends may present an advantage in
      increasing vitamin E potency, as well as decreasing the wear of UHMWPE, which is
      crucial in decreasing the incidence of periprosthetic osteolysis in total joint
      replacement patients.

PMID- 23115034
TI  - PspK of Streptococcus pneumoniae increases adherence to epithelial cells and
      enhances nasopharyngeal colonization.
AB  - Streptococcus pneumoniae (the pneumococcus) colonizes the human nasopharynx and
      can cause invasive disease aided by the pneumococcal capsule. Group II
      nontypeable S. pneumoniae (NTSp) lacks a polysaccharide capsule, and a subgroup
      of NTSp carriage isolates has been found to have a novel gene, pneumococcal
      surface protein K (pspK), which replaces the capsule locus. A recent rise in the
      number of NTSp isolates colonizing the human nasopharynx has been observed, but
      the colonization factors of NTSp have not been well studied. PspK has been shown
      to play a role in mouse colonization. We therefore examined PspK-mediated immune
      evasion along with adherence to host cells and colonization. PspK bound human
      secretory immunoglobulin A (sIgA) but not the complement regulator factor H and
      did not decrease C3b deposition on the pneumococcal surface. PspK increased
      binding of pneumococci to epithelial cells and enhanced pneumococcal colonization
      independently of the genetic background. Understanding how NTSp colonizes and
      survives within the nasopharynx is important due to the increase in NTSp
      carriage. Our data suggest that PspK may aid in the persistence of NTSp within
      the nasopharynx but is not involved in invasion.

PMID- 23115036
TI  - Identification and characterization of the first cholesterol-dependent cytolysins
      from Gram-negative bacteria.
AB  - The cholesterol-dependent cytolysins (CDCs) are pore-forming toxins that have
      been exclusively associated with a wide variety of bacterial pathogens and
      opportunistic pathogens from the Firmicutes and Actinobacteria, which exhibit a
      Gram-positive type of cell structure. We have characterized the first CDCs from
      Gram-negative bacterial species, which include Desulfobulbus propionicus type
      species Widdel 1981 (DSM 2032) (desulfolysin [DLY]) and Enterobacter lignolyticus
      (formerly Enterobacter cloacae) SCF1 (enterolysin [ELY]). The DLY and ELY primary
      structures show that they maintain the signature motifs of the CDCs but lack an
      obvious secretion signal. Recombinant, purified DLY (rDLY) and ELY (rELY)
      exhibited cholesterol-dependent binding and cytolytic activity and formed the
      typical large CDC membrane oligomeric pore complex. Unlike the CDCs from Gram
      positive species, which are human- and animal-opportunistic pathogens, neither D.
      propionicus nor E. lignolyticus is known to be a pathogen or commensal of humans
      or animals: the habitats of both organisms appear to be restricted to anaerobic
      soils and/or sediments. These studies reveal for the first time that the genes
      for functional CDCs are present in bacterial species that exhibit a Gram-negative
      cell structure. These are also the first bacterial species containing a CDC gene
      that are not known to inhabit or cause disease in humans or animals, which
      suggests a role of these CDCs in the defense against eukaryote bacterial
      predators.

PMID- 23115035
TI  - Enterococcus faecalis inhibits hyphal morphogenesis and virulence of Candida
      albicans.
AB  - The Gram-positive bacterium Enterococcus faecalis and the fungus Candida albicans
      are both found as commensals in many of the same niches of the human body, such
      as the oral cavity and gastrointestinal (GI) tract. However, both are
      opportunistic pathogens and have frequently been found to be coconstituents of
      polymicrobial infections. Despite these features in common, there has been little
      investigation into whether these microbes affect one another in a biologically
      significant manner. Using a Caenorhabditis elegans model of polymicrobial
      infection, we discovered that E. faecalis and C. albicans negatively impact each
      other's virulence. Much of the negative effect of E. faecalis on C. albicans was
      due to the inhibition of C. albicans hyphal morphogenesis, a developmental
      program crucial to C. albicans pathogenicity. We discovered that the inhibition
      was partially dependent on the Fsr quorum-sensing system, a major regulator of
      virulence in E. faecalis. Specifically, two proteases regulated by Fsr, GelE and
      SerE, were partially required. Further characterization of the inhibitory signal
      revealed that it is secreted into the supernatant, is heat resistant, and is
      between 3 and 10 kDa. The substance was also shown to inhibit C. albicans
      filamentation in the context of an in vitro biofilm. Finally, a screen of an E.
      faecalis transposon mutant library identified other genes required for
      suppression of C. albicans hyphal formation. Overall, we demonstrate a
      biologically relevant interaction between two clinically important microbes that
      could affect treatment strategies as well as impact our understanding of
      interkingdom signaling and sensing in the human-associated microbiome.

PMID- 23115037
TI  - Adenylate cyclase and the cyclic AMP receptor protein modulate stress resistance
      and virulence capacity of uropathogenic Escherichia coli.
AB  - In many bacteria, the second messenger cyclic AMP (cAMP) interacts with the
      transcription factor cAMP receptor protein (CRP), forming active cAMP-CRP
      complexes that can control a multitude of cellular activities, including expanded
      carbon source utilization, stress response pathways, and virulence. Here, we
      assessed the role of cAMP-CRP as a regulator of stress resistance and virulence
      in uropathogenic Escherichia coli (UPEC), the principal cause of urinary tract
      infections worldwide. Deletion of genes encoding either CRP or CyaA, the enzyme
      responsible for cAMP synthesis, attenuates the ability of UPEC to colonize the
      bladder in a mouse infection model, dependent on intact innate host defenses.
      UPEC mutants lacking cAMP-CRP grow normally in the presence of glucose but are
      unable to utilize alternate carbon sources like amino acids, the primary
      nutrients available to UPEC within the urinary tract. Relative to the wild-type
      UPEC isolate, the cyaA and crp deletion mutants are sensitive to nitrosative
      stress and the superoxide generator methyl viologen but remarkably resistant to
      hydrogen peroxide (H(2)O(2)) and acid stress. In the mutant strains, H(2)O(2)
      resistance correlates with elevated catalase activity attributable in part to
      enhanced translation of the alternate sigma factor RpoS. Acid resistance was
      promoted by both RpoS-independent and RpoS-dependent mechanisms, including
      expression of the RpoS-regulated DNA-binding ferritin-like protein Dps. We
      conclude that balanced input from many cAMP-CRP-responsive elements, including
      RpoS, is critical to the ability of UPEC to handle the nutrient limitations and
      severe environmental stresses present within the mammalian urinary tract.

PMID- 23115038
TI  - Francisella tularensis live vaccine strain folate metabolism and pseudouridine
      synthase gene mutants modulate macrophage caspase-1 activation.
AB  - Francisella tularensis is a Gram-negative bacterium and the causative agent of
      the disease tularemia. Escape of F. tularensis from the phagosome into the
      cytosol of the macrophage triggers the activation of the AIM2 inflammasome
      through a mechanism that is not well understood. Activation of the AIM2
      inflammasome results in autocatalytic cleavage of caspase-1, resulting in the
      processing and secretion of interleukin-1beta (IL-1beta) and IL-18, which play a
      crucial role in innate immune responses to F. tularensis. We have identified the
      5-formyltetrahydrofolate cycloligase gene (FTL_0724) as being important for F.
      tularensis live vaccine strain (LVS) virulence. Infection of mice in vivo with a
      F. tularensis LVS FTL_0724 mutant resulted in diminished mortality compared to
      infection of mice with wild-type LVS. The FTL_0724 mutant also induced increased
      inflammasome-dependent IL-1beta and IL-18 secretion and cytotoxicity in
      macrophages in vitro. In contrast, infection of macrophages with a F. tularensis
      LVS rluD pseudouridine synthase (FTL_0699) mutant resulted in diminished IL-1beta
      and IL-18 secretion from macrophages in vitro compared to infection of
      macrophages with wild-type LVS. In addition, the FTL_0699 mutant was not
      attenuated in vivo. These findings further illustrate that F. tularensis LVS
      possesses numerous genes that influence its ability to activate the inflammasome,
      which is a key host strategy to control infection with this pathogen in vivo.

PMID- 23115039
TI  - Transcriptional modulation of enterotoxigenic Escherichia coli virulence genes in
      response to epithelial cell interactions.
AB  - Enterotoxigenic Escherichia coli (ETEC) strains are a leading cause of morbidity
      and mortality due to diarrheal illness in developing countries. There is
      currently no effective vaccine against these important pathogens. Because genes
      modulated by pathogen-host interactions potentially encode putative vaccine
      targets, we investigated changes in gene expression and surface morphology of
      ETEC upon interaction with intestinal epithelial cells in vitro. Pan-genome
      microarrays, quantitative reverse transcriptase PCR (qRT-PCR), and
      transcriptional reporter fusions of selected promoters were used to study changes
      in ETEC transcriptomes. Flow cytometry, immunofluorescence microscopy, and
      scanning electron microscopy were used to investigate alterations in surface
      antigen expression and morphology following pathogen-host interactions. Following
      host cell contact, genes for motility, adhesion, toxin production, immunodominant
      peptides, and key regulatory molecules, including cyclic AMP (cAMP) receptor
      protein (CRP) and c-di-GMP, were substantially modulated. These changes were
      accompanied by visible changes in both ETEC architecture and the expression of
      surface antigens, including a novel highly conserved adhesin molecule, EaeH. The
      studies reported here suggest that pathogen-host interactions are finely
      orchestrated by ETEC and are characterized by coordinated responses involving the
      sequential deployment of multiple virulence molecules. Elucidation of the
      molecular details of these interactions could highlight novel strategies for
      development of vaccines for these important pathogens.

PMID- 23115040
TI  - Altered Toll-like receptor 9 signaling in Mycobacterium avium subsp.
      paratuberculosis-infected bovine monocytes reveals potential therapeutic targets.
AB  - Mycobacterium avium subsp. paratuberculosis is the causative agent of Johne's
      disease in cattle. The complex, multifaceted interaction of M. avium subsp.
      paratuberculosis with its host includes dampening the ability of infected cells
      to respond to stimuli that promote M. avium subsp. paratuberculosis clearance. By
      disrupting host defenses, M. avium subsp. paratuberculosis creates an
      intracellular environment that favors the establishment and maintenance of
      infection. Toll-like receptors (TLRs) are important sensors that initiate innate
      immune responses to microbial challenge and are also immunotherapeutic targets.
      For example, TLR9 contributes to host defense against M. avium subsp.
      paratuberculosis, and its agonists (CpG oligodeoxynucleotides [ODNs]) are under
      investigation for treatment of Johne's disease and other infections. Here we
      demonstrate that M. avium subsp. paratuberculosis infection changes the
      responsiveness of bovine monocytes to TLR9 stimulation. M. avium subsp.
      paratuberculosis inhibits classical TLR9-mediated responses despite a 10-fold
      increase in TLR9 expression and maintained uptake of CpG ODNs. Other TLR9
      mediated responses, such as oxidative burst, which occur through noncanonical
      signaling, remain functional. Kinome analysis verifies that classic TLR9
      signaling is blocked by M. avium subsp. paratuberculosis infection and that
      signaling instead proceeds through a Pyk2-mediated mechanism. Pyk2-mediated
      signaling does not hinder infection, as CpG ODNs fail to promote M. avium subsp.
      paratuberculosis clearance. Indeed, Pyk2 signaling appears to be an important
      aspect of M. avium subsp. paratuberculosis infection, as Pyk2 inhibitors
      significantly reduce the number of intracellular M. avium subsp. paratuberculosis
      bacteria. The actions of M. avium subsp. paratuberculosis on TLR9 signaling may
      represent a strategy to generate a host environment which is better suited for
      infection, revealing potential new targets for therapeutic intervention.

PMID- 23115041
TI  - Effect of angiotensin II receptor blocker on experimental periodontitis in a
      mouse model of Marfan syndrome.
AB  - Marfan syndrome is an autosomal dominant disease characterized by aneurysm and
      dilatation of the aortic root, tall stature, and ectopia lentis. These
      manifestations reflect excessive signaling of transforming growth factor beta
      (TGF-beta). Moreover, cases are frequently associated with severe periodontitis,
      which is a chronic inflammation of the gingiva, periodontal ligament, and
      alveolar bone. Recently, angiotensin II receptor blockers (ARBs) were discovered
      to be an effective drug class that can prevent aortic aneurysm and dilation in
      Marfan syndrome by inhibiting TGF-beta signaling. To investigate the effect of
      ARB on the progression of periodontitis, the application of a potent ARB,
      telmisartan, was examined in a mouse model of Marfan syndrome (MgDelta). Six-week
      old male heterozygous MgDelta and wild-type mice were challenged with
      Porphyromonas gingivalis, which causes chronic periodontitis, with and without
      telmisartan application. After infection, alveolar bone resorption was measured
      by micro-computed tomography (MUCT), and inflammatory cytokine levels were
      examined. Infection of Porphyromonas gingivalis induced alveolar bone resorption
      in both MgDelta and wild-type mice. The amount of resorption was significantly
      larger in the former than the latter. Immunoarray and enzyme-linked immunosorbent
      assay (ELISA) analyses demonstrated that interleukin-17 (IL-17) and tumor
      necrosis factor alpha (TNF-alpha) levels were significantly higher in infected
      MgDelta mice than infected wild-type mice. Telmisartan treatment significantly
      suppressed the alveolar bone resorption of infected MgDelta mice. Telmisartan
      also significantly decreased levels of TGF-beta, IL-17, and TNF-alpha in infected
      MgDelta mice to levels seen in infected wild-type mice. This study suggests that
      ARB can prevent the severe periodontitis frequently seen in Marfan syndrome.

PMID- 23115042
TI  - Growth of Candida albicans cells on the physiologically relevant carbon source
      lactate affects their recognition and phagocytosis by immune cells.
AB  - Candida albicans is a normal resident of the human gastrointestinal and
      urogenital tracts and also a prevalent fungal pathogen. During both commensalism
      and infection, it must match the immunological defenses of its host while
      adapting to environmental cues and the local nutrient status. C. albicans
      regularly colonizes glucose-poor niches, thereby depending upon alternative
      carbon sources for growth. However, most studies of host immune responses to C.
      albicans have been performed on fungal cells grown on glucose, and the extent to
      which alternative physiologically relevant carbon sources impact innate immune
      responses has not been studied. The fungal cell wall is decorated with
      multifarious pathogen-associated molecular patterns and is the main target for
      recognition by host innate immune cells. Cell wall architecture is both robust
      and dynamic, and it is dramatically influenced by growth conditions. We found
      that growth of C. albicans cells on lactate, a nonfermentative carbon source
      available in numerous anatomical niches, modulates their interactions with immune
      cells and the resultant cytokine profile. Notably, lactate-grown C. albicans
      stimulated interleukin-10 (IL-10) production while decreasing IL-17 levels,
      rendering these cells less visible to the immune system than were glucose-grown
      cells. This trend was observed in clinical C. albicans isolates from different
      host niches and from different epidemiological clades. In addition, lactate-grown
      C. albicans cells were taken up by macrophages less efficiently, but they were
      more efficient at killing and escaping these phagocytic cells. Our data indicate
      that carbon source has a major impact upon the C. albicans interaction with the
      innate immune system.

PMID- 23115043
TI  - Increased susceptibility of melanin-concentrating hormone-deficient mice to
      infection with Salmonella enterica serovar Typhimurium.
AB  - Melanin-concentrating hormone (MCH) was initially identified in mammals as a
      hypothalamic neuropeptide regulating appetite and energy balance. However, the
      wide distribution of MCH receptors in peripheral tissues suggests additional
      functions for MCH which remain largely unknown. We have previously reported that
      mice lacking MCH develop attenuated intestinal inflammation when exposed to
      Clostridium difficile toxin A. To further characterize the role of MCH in host
      defense mechanisms against intestinal pathogens, Salmonella enterocolitis (using
      Salmonella enterica serovar Typhimurium) was induced in MCH-deficient mice and
      their wild-type littermates. In the absence of MCH, infected mice had increased
      mortality associated with higher bacterial loads in blood, liver, and spleen.
      Moreover, the knockout mice developed more-severe intestinal inflammation, based
      on epithelial damage, immune cell infiltrates, and local and systemic cytokine
      levels. Paradoxically, these enhanced inflammatory responses in the MCH knockout
      mice were associated with disproportionally lower levels of macrophages
      infiltrating the intestine. Hence, we investigated potential direct effects of
      MCH on monocyte/macrophage functions critical for defense against intestinal
      pathogens. Using RAW 264.7 mouse monocytic cells, which express endogenous MCH
      receptor, we found that treatment with MCH enhanced the phagocytic capacity of
      these cells. Taken together, these findings reveal a previously unappreciated
      role for MCH in host-bacterial interactions.

PMID- 23115044
TI  - Natural competence promotes Helicobacter pylori chronic infection.
AB  - Animal models are important tools for studies of human disease, but developing
      these models is a particular challenge with regard to organisms with restricted
      host ranges, such as the human stomach pathogen Helicobacter pylori. In most
      cases, H. pylori infects the stomach for many decades before symptoms appear,
      distinguishing it from many bacterial pathogens that cause acute infection. To
      model chronic infection in the mouse, a human clinical isolate was selected for
      its ability to survive for 2 months in the mouse stomach, and the resulting
      strain, MSD132, colonized the mouse stomach for at least 28 weeks. During
      selection, the cagY component of the Cag type IV secretion system was mutated,
      disrupting a key interaction with host cells. Increases in both bacterial
      persistence and bacterial burden occurred prior to this mutation, and a mixed
      population of cagY(+) and cagY mutant cells was isolated from a single mouse,
      suggesting that mutations accumulate during selection and that factors in
      addition to the Cag apparatus are important for murine adaptation. Diversity in
      both alleles and genes is common in H. pylori strains, and natural competence
      mediates a high rate of interstrain genetic exchange. Mutations of the Com
      apparatus, a membrane DNA transporter, and DprA, a cytosolic competence factor,
      resulted in reduced persistence, although initial colonization was normal. Thus,
      exchange of DNA between genetically heterogeneous H. pylori strains may improve
      chronic colonization. The strains and methods described here will be important
      tools for defining both the spectrum of mutations that promote murine adaptation
      and the genetic program of chronic infection.

PMID- 23115045
TI  - Beclin 1 is required for starvation-enhanced, but not rapamycin-enhanced, LC3
      associated phagocytosis of Burkholderia pseudomallei in RAW 264.7 cells.
AB  - LC3-associated phagocytosis (LAP) of Burkholderia pseudomallei by murine
      macrophage (RAW 264.7) cells is an intracellular innate defense mechanism. Beclin
      1, a protein with several roles in autophagic processes, is known to be recruited
      to phagosomal membranes as a very early event in LAP. We sought to determine
      whether knockdown of Beclin 1 by small interfering RNA (siRNA) would affect
      recruitment of LC3 and subsequent LAP of infecting B. pseudomallei. Both
      starvation and rapamycin treatment can induce Beclin 1-dependent autophagy.
      Therefore, we analyzed the consequences of Beclin 1 knockdown for LAP in infected
      cells that had been either starved or treated with rapamycin by determining the
      levels of bacterial colocalization with LC3 and intracellular survival.
      Concurrently, we confirmed the location of bacteria as either contained in
      phagosomes or free in the cytoplasm. We found that both rapamycin and starvation
      treatment enhanced LAP of B. pseudomallei but that the rapamycin response is
      Beclin 1 independent whereas the starvation response is Beclin 1 dependent.

PMID- 23115047
TI  - Overcoming obstacles in Parkinson's disease.
AB  - Improved symptomatic and disease-modifying treatments are needed for Parkinson's
      disease (PD). Although significant advances have been made in the understanding
      of PD etiology, the translation of these discoveries into novel transformative
      therapies has been limited as a result of systemic challenges in PD drug
      development. Preclinical testing lacks clear standards and prioritization
      criteria for advancing therapies to the clinic. Clinical testing is marked by
      expensive, long, and uninformative studies. In parallel to these scientific
      challenges, funding of late-stage drug development has become increasingly scarce
      and risk averse. In this context, novel models of collaboration and funding are
      opening up new avenues for pursuing treatments. This review will discuss the most
      critical challenges in PD drug development and the innovative approaches being
      developed to overcome these hurdles.

PMID- 23115046
TI  - Use of site-directed mutagenesis to model the effects of spontaneous deamidation
      on the immunogenicity of Bacillus anthracis protective antigen.
AB  - Long-term stability is a desired characteristic of vaccines, especially anthrax
      vaccines, which must be stockpiled for large-scale use in an emergency situation;
      however, spontaneous deamidation of purified vaccine antigens has the potential
      to adversely affect vaccine immunogenicity over time. In order to explore whether
      spontaneous deamidation of recombinant protective antigen (rPA)--the major
      component of new-generation anthrax vaccines--affects vaccine immunogenicity, we
      created a "genetically deamidated" form of rPA using site-directed mutagenesis to
      replace six deamidation-prone asparagine residues, at positions 408, 466, 537,
      601, 713, and 719, with either aspartate, glutamine, or alanine residues. We
      found that the structure of the six-Asp mutant rPA was not significantly altered
      relative to that of the wild-type protein as assessed by circular dichroism (CD)
      spectroscopy and biological activity. In contrast, immunogenicity of aluminum
      adjuvanted six-Asp mutant rPA, as measured by induction of toxin-neutralizing
      antibodies, was significantly lower than that of the corresponding wild-type rPA
      vaccine formulation. The six-Gln and six-Ala mutants also exhibited lower
      immunogenicity than the wild type. While the wild-type rPA vaccine formulation
      exhibited a high level of immunogenicity initially, its immunogenicity declined
      significantly upon storage at 25 degrees C for 4 weeks. In contrast, the
      immunogenicity of the six-Asp mutant rPA vaccine formulation was low initially
      but did not change significantly upon storage. Taken together, results from this
      study suggest that spontaneous deamidation of asparagine residues predicted to
      occur during storage of rPA vaccines would adversely affect vaccine
      immunogenicity and therefore the storage life of vaccines.

PMID- 23115048
TI  - Adult hyperglycemic crisis: a review and perspective.
AB  - Hyperglycemic crisis, which includes Diabetic Ketoacidosis and Hyperglycemic
      Hyperosmolar State, is a common diagnosis in high acuity hospital units and
      admission rates continue to increase despite preventive strategies. While
      diabetic ketoacidosis remains a common cause of death in children and adolescents
      with type 1 diabetes, in adults reported mortality is variable and depends on the
      severity of metabolic derangement and the presence of other acute and chronic
      conditions. Hyperosmolar hyperglycemic state, and the overlap syndrome of
      hyperosmolar ketoacidosis, have a higher overall mortality though outcomes are
      improving. We discuss the diagnosis, epidemiology, and management strategies with
      particular reference to commonly encountered pitfalls in care and provide an
      updated perspective on the shifts in the epidemiology and novel management
      strategies for these important disorders.

PMID- 23115050
TI  - Non-CpG island promoter hypomethylation and miR-149 regulate the expression of
      SRPX2 in colorectal cancer.
AB  - Gene silencing by DNA hypermethylation of CpG islands is a well-characterized
      phenomenon in cancer. The effect of hypomethylation in particular of non-CpG
      island genes is much less well described. By genome-wide screening, we identified
      105 genes in microsatellite stable (MSS) colorectal adenocarcinomas with an
      inverse correlation (Spearman's rho <= -0.40) between methylation and expression.
      Of these, 35 (33%) were hypomethylated non-CpG island genes and two of them,
      APOLD1 (Spearman's rho = -0.82) and SRPX2 (Spearman's rho = -0.80) were selected
      for further analyses. Hypomethylation of both genes were localized events not
      shared by adjacent genes. A set of 662 FFPE DNA samples not only confirmed that
      APOLD1 and SRPX2 are hypomethylated in CRC but also revealed hypomethylation to
      be significantly (p < 0.01) associated with tumors being localized in the left
      side, CpG island methylator phenotype negative, MSS, BRAF wt, undifferentiated
      and of adenocarcinoma histosubtype. Demethylation experiments supported SRPX2
      being epigenetically regulated via DNA methylation, whereas other mechanisms in
      addition to DNA methylation seem to be involved in the regulation of APOLD1. We
      further identified miR-149 as a potential novel post-transcriptional regulator of
      SRPX2. In carcinoma tissue, miR-149 was downregulated and inversely correlated to
      SRPX2 (rho = -0.77). Furthermore, ectopic expression of miR-149 significantly
      reduced SRPX2 transcript levels. Our study highlights that in colorectal tumors,
      hypomethylation of non-CpG island-associated promoters deregulate gene expression
      nearly as frequent as do CpG-island hypermethylation. The hypomethylation of
      SRPX2 is focal and not part of a large block. Furthermore, it often translates to
      an increased expression level, which may be modulated by miR-149.

PMID- 23115049
TI  - Copper signaling in the mammalian nervous system: synaptic effects.
AB  - Copper is an essential metal present at high levels in the CNS. Its role as a
      cofactor in mitochondrial ATP production and in essential cuproenzymes is well
      defined. Menkes and Wilson's diseases are severe neurodegenerative conditions
      that demonstrate the importance of Cu transport into the secretory pathway. In
      the brain, intracellular levels of Cu, which is almost entirely protein bound,
      exceed extracellular levels by more than 100-fold. Cu stored in the secretory
      pathway is released in a Ca(2+)-dependent manner and can transiently reach
      concentrations over 100 MUM at synapses. The ability of low micromolar levels of
      Cu to bind to and modulate the function of gamma-aminobutyric acid type A
      (GABA(A)) receptors, N-methyl-D-aspartate (NMDA) receptors, and voltage-gated
      Ca(2+) channels contributes to its effects on synaptic transmission. Cu also
      binds to amyloid precursor protein and prion protein; both proteins are found at
      synapses and brain Cu homeostasis is disrupted in mice lacking either protein.
      Especially intriguing is the ability of Cu to affect AMP-activated protein kinase
      (AMPK), a monitor of cellular energy status. Despite this, few investigators have
      examined the direct effects of Cu on synaptic transmission and plasticity.
      Although the variability of results demonstrates complex influences of Cu that
      are highly method sensitive, these studies nevertheless strongly support
      important roles for endogenous Cu and new roles for Cu-binding proteins in
      synaptic function/plasticity and behavior. Further study of the many roles of Cu
      in nervous system function will reveal targets for intervention in other diseases
      in which Cu homeostasis is disrupted.

PMID- 23115051
TI  - Enlarged hyperechogenic substantia nigra as a risk marker for Parkinson's
      disease.
AB  - BACKGROUND: SN hyperechogenicity (SN+), determined by transcranial sonography,
      has been proposed as a risk factor for Parkinson's disease (PD). Recently, we
      reported a 17.4-fold increased risk for PD in individuals with SN+ older than 50
      years within 3 years. METHODS: This is the second follow-up of a prospective,
      longitudinal, three-center observational study after 5 years. Of the initial
      1,847 at baseline PD-free participants 50 years or older, 1,271 underwent the 5
      year reassessment. RESULTS: Within 5 years, 21 individuals developed incident PD.
      Participants with SN+ at baseline had a more than 20.6 times increased risk to
      develop PD in this time span than those without this echo feature. CONCLUSION: We
      thus confirm our finding of the 3-year follow-up examination in a longer
      observation time and higher number of individuals with incident PD and suggest
      SN+ as an important risk marker for PD.

PMID- 23115052
TI  - Plasma-derived tumor DNA analysis at whole-genome resolution.

PMID- 23115053
TI  - Validating serum markers for monitoring of cancer.

PMID- 23115054
TI  - Noninvasive prenatal determination of twin zygosity by maternal plasma DNA
      analysis.
AB  - BACKGROUND: The current methods for distinguishing the zygosities of twins
      include ultrasound scanning, which is nondefinitive, and amniocentesis, which is
      invasive. We explored the use of massively parallel sequencing of maternal plasma
      DNA for the noninvasive prenatal assessment of the zygosities of twin
      pregnancies. METHODS: Plasma DNA was extracted from blood collected from 8 women
      pregnant with twins. Target enrichment and massively parallel sequencing were
      performed for each plasma DNA library. Apparent fractional fetal DNA
      concentrations were calculated for multiple genomic regions by determining the
      ratio of minor to major alleles among single-nucleotide polymorphism sites.
      Variations in the apparent fractional fetal DNA concentrations between genomic
      regions were used to infer whether individual fetuses in a twin pair were
      genotypically different and hence dizygotic. RESULTS: The extent of the variation
      in the apparent fractional fetal DNA concentration across chromosomes was 0.82
      1.35 SDs for monozygotic twin pregnancies and 2.42-4.80 SDs for dizygotic twin
      pregnancies. The proportions of apparent fractional fetal DNA concentration
      values that deviated beyond the range expected for stochastic variation were
      0.00%-1.93% for monozygotic twin pregnancies and 36.2%-78.1% for dizygotic twin
      pregnancies. After identifying a pair of twins as likely dizygotic, the method
      also allowed determination of the fractional fetal DNA concentrations contributed
      by the individual fetuses of a dizygotic twin pair. CONCLUSIONS: Noninvasive
      prenatal determination of twin zygosity by maternal plasma DNA sequencing is
      feasible. It is also possible to determine the relative fractional fetal DNA
      concentrations for each fetus for dizygotic twin pregnancies.

PMID- 23115055
TI  - Comparing multiple measures of glycemia: how to transition from biomarker to
      diagnostic test?

PMID- 23115056
TI  - Cobalt and chromium measurement in patients with metal hip prostheses.

PMID- 23115057
TI  - The biology of brain metastasis.
AB  - BACKGROUND: It is estimated that at least 200 000 cases of brain metastases occur
      each year in the US, which is 10 times the number of patients diagnosed with
      primary brain tumors. Brain metastasis is associated with poor prognosis,
      neurological deterioration, diminished quality of life, and extremely short
      survival. Favorable interactions between tumor cells and cerebral microvascular
      endothelial cells encourage tumor growth in the central nervous system, while
      tumor cell interactions with astrocytes protect brain metastases from the
      cytotoxic effects of chemotherapy. CONTENT: We review the pathogenesis of brain
      metastasis and emphasize the contributions of microvascular endothelial cells and
      astrocytes to disease progression and therapeutic resistance. Animal models used
      to study brain metastasis are also discussed. SUMMARY: Brain metastasis has many
      unmet clinical needs. There are few clinically relevant tumor models and no
      targeted therapies specific for brain metastases, and the mean survival for
      untreated patients is 5 weeks. Improved clinical outcomes are dependent on an
      enhanced understanding of the metastasis-initiating population of cells and the
      identification of microenvironmental factors that encourage disease progression
      in the central nervous system.

PMID- 23115058
TI  - IsoPCR: an analytically sensitive, nested, multiplex nucleic acid amplification
      method.
AB  - BACKGROUND: Nucleic acid tests that can simultaneously detect multiple targets
      with high sensitivity, specificity, and speed are highly desirable. To meet this
      need, we developed a new approach we call the isoPCR method. METHODS: The isoPCR
      method is a 2-stage nested-like nucleic acid amplification method that combines a
      single multiplex preamplification PCR with subsequent distinct detection of
      specific targets by use of isothermal amplification. We compared isoPCR to nested
      quantitative PCR (qPCR), loop-mediated isothermal amplification (LAMP), and
      nested LAMP (PCR followed by LAMP), for detection of DNA from Candida glabrata.
      We evaluated the method's multiplex capability for detecting low copy numbers of
      pathogens commonly involved in sepsis. RESULTS: IsoPCR provided detection of 1
      copy of Candida glabrata, an LOD that was 5-fold lower than a nested qPCR assay
      (5 copies), while the amplification time was simultaneously halved. Similarly,
      the LOD for isoPCR was lower than that for a LAMP assay (1000 copies) and a
      nested LAMP assay (5 copies). IsoPCR required recognition of 6 regions for
      detection, thereby providing a theoretically higher specificity compared to
      nested qPCR (4 regions). The isoPCR multiplexing capability was demonstrated by
      simultaneous detection of 4 pathogens with individual LODs of 10 copies or fewer.
      Furthermore, the specificity of isoPCR was demonstrated by successful pathogen
      detection from samples with more than 1 pathogen present. CONCLUSIONS: IsoPCR
      provides a molecular diagnostic tool for multiplex nucleic acid detection, with
      an LOD down to 1 copy, high theoretical specificity, and halving of the
      amplification time compared to a nested qPCR assay.

PMID- 23115059
TI  - Neuroprotective action and free radical scavenging activity of Guttiferone-A, a
      naturally occurring prenylated benzophenone.
AB  - Reactive oxygen species (ROS) are important mediators in a number of
      neurodegenerative diseases and molecules capable of scavenging ROS may be a
      feasible strategy for protecting neuronal cells. We previously demonstrated a
      powerful iron-chelating action of Guttiferone-A (GA), a naturally occurring
      polyphenol, on oxidative stress injuries initiated by iron overload. Here we
      addressed the neuroprotective potential of GA in hydrogen peroxide and glutamate
      induced injury on rat's primary culture of cortical neurons and PC12 cells,
      respectively, and antioxidant properties concerning scavenging and anti
      lipoperoxidative activities in cell-free models. The decrease in cell viability
      induced by each of the toxins, assessed by [3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyl tetrazolium bromide] (MTT) assay, was significantly attenuated by GA. In
      addition, GA was found to be a potent antioxidant, as shown by (i) inhibition of
      1,1-diphenyl-2-picrylhydrazyl (DPPH) radical reduction (EC50=20.0 MUM), (ii)
      prevention against chemically or electrochemically generated superoxide radicals,
      (iii) inhibition of spontaneous brain lipid peroxidation and (iv) interference
      with the Fenton reaction. These results indicate that GA exerts neuroprotective
      effects against H2O2 or glutamate toxicity and its antioxidant activity,
      demonstrated in vitro, could be at least partly involved. They also suggest a
      promising potential for GA as a therapeutic agent against neurodegenerative
      diseases involving ROS and oxidative damage.

PMID- 23115060
TI  - The effect of ethyl alcohol on the function of spatial memory in rats.
AB  - Alcoholism is a mental disease in the course of which depression, anxiety, and
      cognitive function deficits may appear, and these symptoms can be aggravated by
      comorbid schizophrenia.The aim of this study was to find whether spatial memory
      (Morris Water Maze) function impairment is found in prenatally stressed rats
      (PSG) (prenatal stress paradigm - animal model of schizophrenia) and whether
      aripiprazole ARI and olanzapine OLA modify these functions. It was also important
      to study the effect of ethyl alcohol administered to rats.Behavioural tests
      showed that ARI and OLA improved spatial memory in the non-stressed control group
      (NSCG) and in the PSG. Moreover, spatial memory in the non-stressed alcohol group
      (NSAG) improved significantly compared to the NSCG, while in the prenatally
      stressed alcohol group (PSAG) spatial memory improved both in comparison to the
      NSCG and PSG. No statistically significant differences were found by comparing
      groups which received ethyl alcohol (NSAG, PSAG).

PMID- 23115061
TI  - Biocompatibility and strength retention of biodegradable Mg-Ca-Zn alloy bone
      implants.
AB  - The biocompatibility and strength retention of a Mg-Ca-Zn alloy were studied to
      evaluate its efficacy for osteosynthesis applications. Mg-Ca-Zn alloy and self
      reinforced poly l-lactide (SR-PLLA) bone screws were implanted into New Zealand
      rabbits for radiography analysis, micro computed tomography analysis,
      histomorphometry, hematology, serum biochemistry, histopathology, and inductively
      coupled plasma mass spectrometry analysis. Bending and torsion tests were
      performed on intact specimens to find the initial mechanical strength of these Mg
      Ca-Zn alloy bone screws. Strength retention of the Mg-Ca-Zn alloy implants were
      calculated from in vivo degradation rates and initial mechanical strength. Based
      on the animal study, Mg-Ca-Zn alloy bone screw showed absence of subcutaneous gas
      pockets, characteristic surface erosion properties, faster degradation rate than
      SR-PLLA bone screw, normal reference range of hematology and serum biochemistry,
      better histopathological response than SR-PLLA bone screw, and stable
      concentrations of each constituent element in soft tissues surrounding the
      implants. The initial strength and strength retention of Mg-Ca-Zn alloy were
      compared with those of various biomaterials. The initial strength of Mg-Ca-Zn
      alloy was higher than those of biostable and biodegradable polymers. The strength
      retention of Mg-Ca-Zn alloy bone screws was similar to those of biodegradable
      polymer. Therefore, this Mg-Ca-Zn alloy represents an excellent biodegradable
      biomaterial candidate for osteosynthesis applications.

PMID- 23115062
TI  - Patients with sickle cell disease have increased sensitivity to cold and heat.
AB  - Sickle cell disease (SCD) pain is associated with colder temperatures and touch
      and described as "cold," "hot," and "shooting" suggesting hypersensitivity to
      tactile stimuli. Sickle mice exhibit hypersensitivity to thermal (cold, heat) and
      mechanical stimuli compared to controls. It is unknown whether humans experience
      this same hypersensitivity. Thus, we quantified thermal and mechanical
      sensitivity differences between patients with SCD and controls. Our primary
      hypothesis was that patients with SCD will exhibit hypersensitivity to thermal
      and mechanical stimuli compared to race-matched controls. Our secondary
      hypothesis was this hypersensitivity will be associated with older and female
      subjects, and with frequent pain and hemolysis in patients with SCD. A total of
      55 patients and 57 controls >=7 years completed quantitative sensory testing.
      Patients with SCD detected the sensation of cold and warm temperatures sooner as
      seen in their significantly lower median cold and heat detection thresholds [29.5
      degrees C vs. 28.6 degrees C, P = 0.012 and 34.5 degrees C vs. 35.3 degrees C, P
      = 0.02] and experienced cold and heat pain sooner as seen in their significantly
      lower median cold and heat pain thresholds [21.1 degrees C vs. 14.8 degrees C, P
      = 0.01 and 42.7 degrees C vs. 45.2 degrees C, P = 0.04]. We found no mechanical
      threshold differences. Older age was associated with lower cold, heat, and
      mechanical pain thresholds in both groups. No association with pain, gender, or
      hemolysis was found. Patients with SCD exhibit hypersensitivity to thermal
      stimuli suggesting peripheral or central sensitization may exist and could
      contribute to SCD pain.

PMID- 23115063
TI  - Known glioma risk loci are associated with glioma with a family history of brain
      tumours -- a case-control gene association study.
AB  - Familial cancer can be used to leverage genetic association studies. Recent
      genome-wide association studies have reported independent associations between
      seven single nucleotide polymorphisms (SNPs) and risk of glioma. The aim of this
      study was to investigate whether glioma cases with a positive family history of
      brain tumours, defined as having at least one first- or second-degree relative
      with a history of brain tumour, are associated with known glioma risk loci. One
      thousand four hundred and thirty-one glioma cases and 2,868 cancer-free controls
      were identified from four case-control studies and two prospective cohorts from
      USA, Sweden and Denmark and genotyped for seven SNPs previously reported to be
      associated with glioma risk in case-control designed studies. Odds ratios were
      calculated by unconditional logistic regression. In analyses including glioma
      cases with a family history of brain tumours (n = 104) and control subjects free
      of glioma at baseline, three of seven SNPs were associated with glioma risk:
      rs2736100 (5p15.33, TERT), rs4977756 (9p21.3, CDKN2A-CDKN2B) and rs6010620
      (20q13.33, RTEL1). After Bonferroni correction for multiple comparisons, only one
      marker was statistically significantly associated with glioma risk, rs6010620
      (ORtrend for the minor (A) allele, 0.39; 95% CI: 0.25-0.61; Bonferroni adjusted
      ptrend , 1.7 * 10(-4) ). In conclusion, as previously shown for glioma regardless
      of family history of brain tumours, rs6010620 (RTEL1) was associated with an
      increased risk of glioma when restricting to cases with family history of brain
      tumours. These findings require confirmation in further studies with a larger
      number of glioma cases with a family history of brain tumours.

PMID- 23115064
TI  - Long-term course of substantia nigra hyperechogenicity in Parkinson's disease.
AB  - A hyperechogenicity of the (SN+) in transcranial sonography corroborates the
      diagnosis of idiopathic Parkinson's disease (iPD). Although it is thought to
      represent a biomarker of the disease that is independent of disease severity and
      progression, differing results have been reported describing a positive
      correlation of the size and advancing clinical stage. In 50 parkinsonian
      patients, transcranial ultrasound and clinical examination was performed twice
      with a mean time interval of 6.4 years. SN+ did not change in size significantly
      between the first and second examination, whereas clinical parkinsonian symptoms-
      as determined by the motor part of the UPDRS--significantly worsened (P < 0.001).
      We found a highly significant intraindividual correlation in SN+ sizes between
      both examinations (P < 0.001). The size of SN+ did not correlate with the UPDRS
      part III at the time of first or second ultrasound examination. Progression of
      motor symptoms between the first and second investigation did not correlate with
      the size of SN+ at baseline. Furthermore, even in the subgroup of patients with
      an interval of >= 8 years between examinations, there was no significant change
      in SN+ size. SN+ represents a largely stable biomarker in iPD and does not
      reflect disease progression. The size of SN+ does not predict the further course
      of the disease.

PMID- 23115065
TI  - Tailoring of processing parameters for sintering microsphere-based scaffolds with
      dense-phase carbon dioxide.
AB  - Microsphere-based polymeric tissue-engineered scaffolds offer the advantage of
      shape-specific constructs with excellent spatiotemporal control and
      interconnected porous structures. The use of these highly versatile scaffolds
      requires a method to sinter the discrete microspheres together into a cohesive
      network, typically with the use of heat or organic solvents. We previously
      introduced subcritical CO(2) as a sintering method for microsphere-based
      scaffolds; here we further explored the effect of processing parameters. Gaseous
      or subcritical CO(2) was used for making the scaffolds, and various pressures,
      ratios of lactic acid to glycolic acid in poly(lactic acid-co-glycolic acid), and
      amounts of NaCl particles were explored. By changing these parameters, scaffolds
      with different mechanical properties and morphologies were prepared. The
      preferred range of applied subcritical CO(2) was 15-25 bar. Scaffolds prepared at
      25 bar with lower lactic acid ratios and without NaCl particles had a higher
      stiffness, while the constructs made at 15 bar, lower glycolic acid content, and
      with salt granules had lower elastic moduli. Human umbilical cord mesenchymal
      stromal cells (hUCMSCs) seeded on the scaffolds demonstrated that cells penetrate
      the scaffolds and remain viable. Overall, the study demonstrated the dependence
      of the optimal CO(2) sintering parameters on the polymer and conditions, and
      identified desirable CO(2) processing parameters to employ in the sintering of
      microsphere-based scaffolds as a more benign alternative to heat-sintering or
      solvent-based sintering methods.

PMID- 23115066
TI  - Adiponectin, leptin, resistin and insulin blood concentrations in patients with
      ischaemic cerebral stroke.
AB  - INTRODUCTION: Stroke, due to its worldwide prevalence, is not only a medical
      challenge, but also a serious social problem. Recently, ongoing research has
      examined whether there are associations between adipose tissue hormones and the
      risk, mechanisms and course of stroke. The aim of our study was to determine
      whether there are significant differences in blood concentrations of insulin,
      adiponectin, leptin, resistin and in insulin resistance among patients in the
      acute phase of ischaemic stroke, compared to healthy subjects. In addition, we
      wanted to investigate if those biochemical values show a correlation with the
      neurological condition of our patients. MATERIAL AND METHODS: Adiponectin,
      leptin, resistin and insulin were measured in patients (n = 69) with first-ever
      ischaemic stroke (confirmed by CT), using specific electrochemoluminescence,
      radioimmunoassay and ELISA methods. Neurological evaluation was performed using
      Barthel ADL index on the day of admission and on the ninth day of
      hospitalisation. Insulin resistance value was obtained via the HOMA-IR
      calculator. Data was compared to that of healthy individuals (n = 26). RESULTS:
      Insulin concentration (51.08 v. 17.02 uU/mL) and HOMA-IR value (6.3 v. 2.2) were
      significantly higher in the study group. Leptin (14.98 v. 10.47 ng/mL) and
      resistin (28.92 v. 12.25 ng/mL) levels were elevated among the stroke survivors
      compared to controls, but no significant difference was noted in adiponectin.
      Negative correlations of adiponectin level and Barthel score were observed.
      CONCLUSIONS: Hyperinsulinaemia and insulin resistance are involved in the
      pathogenesis of ischaemic stroke. Hyperleptinaemia and hyperresistinaemia play a
      role in the mechanism of stroke. The severity of stroke is associated with
      adiponectin blood concentration.

PMID- 23115067
TI  - Thyroid dysfunction and thyroid autoimmunity in a large unselected population of
      elderly subjects in Poland - the 'PolSenior' multicentre crossover study.
AB  - INTRODUCTION: Data on the thyroid function of a randomly chosen elderly
      population was collected during a multicentre study performed in Poland
      (PolSenior) in 2007-2010. MATERIAL AND METHODS: The population of 4,190
      participants under study was divided into six age subgroups of > 65 to > 90 years
      of age and a younger group aged between 55 and 59 years. Assessment of thyroid
      function was based on hormonal measurements. RESULTS: Concentrations of both TSH
      and fT(4) were significantly higher in females than in males. No differences in
      TSH and fT(4) concentrations between different age groups were found. Thyroid
      dysfunction was revealed in more than 10% of participants, hypothyroidism in
      7.95%, and hyperthyroidism in 2.95%. Both types of dysfunction were more
      prevalent in women, and in more than 80% both dysfunctions were subclinical. In
      1,542 participants, concentrations of TPOAb were measured. Increased TPOAb was
      revealed in 19% of the cohort and the prevalence of thyroid autoimmunity was
      higher in women and also more often found in participants with hypothyroidism.
      CONCLUSIONS: Cross sectional survey revealed thyroid dysfunctions in over 10% of
      non selected elderly population. No age related differences were found in TSH
      concentrations, TPOAb positivity and prevalence of thyroid dysfunctions.

PMID- 23115068
TI  - Insulin-like factor 3 -- a new hormone related to polycystic ovary syndrome?
AB  - INTRODUCTION: The aim of this study was to find a correlation between insulin
      like factor 3 (INSL3) and androgens: androstenedione (A), free testosterone (fT),
      and total testosterone (T), in two groups of polycystic ovary syndrome (PCOS)
      women: those with a body mass index (BMI) lower than 25 kg/m(2) and those with a
      BMI higher than 25 kg/m(2). The association between INSL3 and other serum
      parameters: luteinising hormone (LH), follicle-stimulating hormone (FSH),
      dehydroepiandrosterone sulphate (DHEA-S), sex hormone binding globulin (SHBG) and
      glucose and insulin were also investigated. MATERIAL AND METHODS: The study group
      comprised 37 PCOS women aged 27 +/- 4 years. The control group consisted of 34
      healthy, premenopausal women (aged 24.2 +/- 1.2) with regular menses and no signs
      of hyperandrogenism. There were 27 PCOS women of normal weight (BMI < 25
      kg/m(2)), and ten overweight individuals (BMI >= 25-30 kg/m(2)). Correlations
      between level of INSL3 and LH, FSH, T, fT, A, DHEA-S, SHBG, metabolic tests,
      height, weight, and WHR (waist-to-hip ratio) were also investigated. RESULTS:
      PCOS women showed non-significantly higher levels of INSL3 compared to the
      healthy controls (64.6 +/- 27.7 and 62.7 +/- 20.0 ng/mL, respectively). However,
      we identified very strong correlations between INSL3 and androstenedione (r =
      0.48, p = 0.0115), and free (r = 0.44, p = 0.0108) and total testosterone (r =
      0.46, p = 0.0057) in the PCOS subgroup with a BMI of < 25 kg/m(2). There was no
      statistically significant correlation between INSL3 and LH in any subject of the
      PCOS group, nor between INSL3 and FSH, DHEA-S, glucose, basal insulin
      concentration or HOMA-IR. CONCLUSIONS: We found a positive correlation between
      INSL3 and androgens in PCOS women, especially those with a BMI of < 25 kg/m(2).
      This may play a key role in PCOS pathophysiology.

PMID- 23115069
TI  - The value of the Ki-67 proliferation marker as a prognostic factor in
      gastroenteropancreatic neuroendocrine tumours.
AB  - INTRODUCTION: Gastroenteropancreatic neuroendocrine tumours (GEP NETs) are a
      heterogenous group of tumours of various clinical presentations. Proliferative
      activity of tumour cells is an essential parameter determining the course of the
      disease and affecting the prognosis. The Ki-67 antigen is an important marker of
      cell proliferation, which shows activity in all the phases of the cell cycle,
      excluding the G0 phase. AIM OF THE STUDY: To assess the expression of Ki-67 in
      GEP NETs and to examine the association of Ki-67 with the stage of the tumour
      (tumour size, presence of metastases) and the hormonal function of the tumour.
      MATERIAL AND METHODS: We included 61 patients with GEP NETs (25 males and 36
      females aged between 20 and 82 years [mean age: 56 years]). The proliferative
      activity was examined in paraffin blocks containing surgically removed tumour
      samples and in core-needle biopsies of primary and metastatic tumours. The
      presence of the Ki-67 antigen was assessed by immunohistochemistry using MIB-1
      monoclonal antibodies. Based on the Ki-67 proliferative index we determined the
      tumour grade. In addition, we determined the tumour stage according to the TNM
      classification. In all the subjects we determined the levels of the non-specific
      NET marker (chromogranin A) and of specific NET markers (serotonin, insulin and
      gastrin in the blood and 5-hydroxyindoleacetic acid [5-HIAA] in 24-hour urine).
      RESULTS: The diagnoses of low-grade (Ki-67 <= 2%), intermediate-grade (Ki-67 3
      20%) and high-grade (Ki-67 > 20%) NET were established in 38, 12 and 11 patients,
      respectively. Metastatic disease was diagnosed in 36/61 patients. A significantly
      higher expression of K-67 was observed in patients with metastatic disease (p =
      0.01). A positive correlation was demonstrated between Ki-67 and the stage of the
      disease (p = 0.01) and between the histologic grade of the tumour and the stage
      of the disease (p = 0.01). No association between Ki-67 and the levels of
      chromogranin A, serotonin, insulin, gastrin and 5-HIAA was shown. There was also
      no difference in Ki-67 expression relative to the location of the primary tumour
      and the tumour size. CONCLUSIONS: The Ki-67 proliferative index is an essential
      parameter predicting the course of GEP-NETs.

PMID- 23115070
TI  - Glycated haemoglobin is correlated with the severity of coronary artery disease
      independently of traditional risk factors in young patients.
AB  - INTRODUCTION: In this study, we aimed to investigate the relationship between
      glycated haemoglobin (HbA1c) levels and the severity of coronary artery disease
      (CAD) in < 40 years old patients. MATERIAL AND METHODS: The study population
      consisted of 211 premature coronary atherosclerotic patients (pCAP) (aged 36.4 +/
      2.5 years) and 160 control subjects (36.4 +/- 2.4 years). The severity of CAD
      was evaluated by the Gensini scoring system. HbA1c levels and the other basic
      biochemical parameters were analysed, and relations with severity of CAD were
      evaluated. RESULTS: There were statistically significant differences in serum
      HbA1c levels between the two groups (pCAP = 6.1 +/- 1.8%, control = 4.7 +/- 1.2%,
      p < 0.001). HbA1c levels significantly positively correlated with the Gensini
      score in pCAP (r = 0.662, p < 0.001). In linear multivariate regression analysis
      (including age, sex, HbA1c, smoking, diabetes mellitus and hypertension as
      dependent parameters), only HbA1c was found to be an independent risk factor for
      the presence of severe CAD (Beta = 0.374, p < 0.001). In ROC curve analysis, the
      optimal cut-off value of HbA1c to predict severe CAD was 6.52%, with 74.4%
      sensitivity and 75.1% specificity (area under the curve 0.781, 95% confidence
      interval 0.661 to 0.901, p < 0.001). CONCLUSIONS: HbA1c levels were found to be
      correlated with the Gensini score in pCAP with and without diabetes. In this
      respect, glucose metabolism abnormalities, indicated by HbA1c, may play an
      important role in premature CAD.

PMID- 23115071
TI  - Incidence of metabolic syndrome and its risk factors among type 2 diabetes clinic
      attenders in Isfahan, Iran.
AB  - INTRODUCTION: At present, little data exists about the incidence of, and the risk
      factors associated with, metabolic syndrome (MetS) in patients with type 2
      diabetes mellitus (T2DM). The aims of this present study were to assess the
      incidence and risk factors of MetS in people with T2DM using routinely collected
      data from a clinical information system at Isfahan Endocrine and Metabolism
      Research Centre, Iran. MATERIAL AND METHODS: During the mean (SD) follow-up
      period of 11.7 (4.8) years, 3,047 patients with T2DM who were free of MetS at
      baseline were examined to determine the incidence and predictors of progression
      to MetS. The mean (SD) age of participants was 50.4 (11.0) years, with a mean
      (SD) duration of diabetes of 6.3 (6.2) years at initial registration. A modified
      National Cholesterol Education Programme- Adult Treatment Panel III definition
      (with body mass index [BMI] instead of waist circumference) was used for the
      MetS. RESULTS: The prevalence of MetS was 63.2% (95% CI: 62.3, 64.1). The
      incidence of MetS was 28.5 (95% CI: 26.8, 30.2) (25.9 men and 30.9 women) per
      1,000 patient-years based on 35,677 patient-years of follow-up. Multivariate
      analysis revealed that higher body mass index (BMI) and education, lower HbA1c
      and treatment with oral agent or insulin were associated with MetS. CONCLUSIONS:
      These are the first estimates of the incidence and risk factors of MetS in
      patients with T2DM in Iran. These findings show that the natural course of MetS
      is dynamic. The clinical management of patients with T2DM will contribute
      significantly to MetS prevention.

PMID- 23115072
TI  - Effect of breath-hold diving (freediving) on serum androgen levels -- a
      preliminary report.
AB  - INTRODUCTION: Breath-hold diving (freediving) is a discipline that makes
      considerable demands on sportsmen, which can amount to extreme distress. It is
      also known that psychological and physical strain affects hormonal milieus. We
      wanted to assess the impact of a stressful event (such as breath-hold diving) on
      the androgen status of men. MATERIAL AND METHODS: We evaluated serum
      gonadotropins and androgen concentrations in four divers before diving,
      immediately post, and 60 minutes after diving. RESULTS: We found that neither
      gonadotropins nor total testosterone, free testosterone, calculated free
      testosterone or bioavailable testosterone concentrations changed significantly
      during diving practice. CONCLUSIONS: We conclude that the acute distress
      associated with breath-hold diving does not impact upon gonadotropins or androgen
      concentrations.

PMID- 23115073
TI  - Mixed germ cells tumour primarily located in the thyroid -- a case report.
AB  - Germ cells tumours most frequently occur in the gonads. Extragonadal localisation
      is rare and concerns mainly the mediastinum, retroperitoneum and pineal. We
      present the first description of a patient with a mixed germ cells tumour located
      primarily in the thyroid. A 35-year-old man in a good clinical condition was
      admitted to diagnose metastasis revealed in an X-ray of his lungs. Abnormal
      laboratory tests showed high concentrations of beta-HCG and LDH. Ultrasound
      examination revealed: hypoechogenic area 8 * 4 * 5 mm in the left testicle, and
      enlarged left thyroid lobe with echogenically heterogenous mass. In cytological
      examination of the thyroid, carcinomatous cells were found, which suggested
      metastasis. A diagnosis of cancerous spread of testicular cancer to the lungs and
      thyroid was made. The left testicle, with spermatic cord, was removed, yet in the
      histopathological examination no carcinomatous cells were found. Rescue
      chemotherapy, according to the BEP scheme (bleomycin, etoposide, cisplatin) was
      started, but during its course the patient died. Histopathology disclosed primary
      mixed germ cells tumour in the thyroid, predominantly with carcinoma embryonale
      and focuses of choriocarcinoma. Extragonadal germ cells tumours rarely occur in
      the thyroid. In medical literature, some cases of teratomas and a single case of
      yolk sac tumour in the thyroid have been described. The presence of
      choriocarcinoma was responsible for the high serum concentration of beta-HCG.
      Surgery of germ cells tumours proves insufficient. The conventional chemotherapy
      is based on cisplatin. In conclusion, extragonadal germ cells tumours are rare,
      but should be considered while co-existing with elevated markers such as: AFP,
      beta-HCG and lack of abnormalities in the gonads.

PMID- 23115074
TI  - Pheochromocytoma of the adrenal gland selectively secreting dopamine -- a case
      report.
AB  - Pheochromocytoma of the adrenal gland secreting catecholamines is a relatively
      rare endocrinological cause of secondary arterial hypertension, usually
      developing in people aged between 40 and 50, more often in women than in men.
      Each accidentally diagnosed lesion in adrenal glands is an incidentalom0a.
      Incidentalomas are most commonly benign tumours: adenomas, adipomas and angiomas;
      less often they are of a malignant or metastatic character. Establishing the
      character of the lesion and its hormonal activity is of crucial diagnostic
      significance. Diagnostics of pheochromocytoma covers marking the urine output of
      catecholamines and their metabolites, as well as marking serum amine
      concentration. Possible treatment of hormonally active lesions includes their
      surgical removal. This thesis presents the case of a young female suffering from
      arterial hypertension for several years, including organ complications, who was
      diagnosed with pheochromocytoma selectively secreting dopamine.

PMID- 23115075
TI  - Cushing's disease -- assessing the efficacy of transsphenoidal surgery.
AB  - Cushing's disease (CD) is caused by a pituitary adenoma secreting corticotrophin
      (ACTH) that leads to cortisol excess. Despite a characteristic clinical picture,
      it is often difficult to make a proper diagnosis, as it requires complex and long
      lasting diagnostic procedures. Selective transsphenoidal surgery (TSS) remains
      the treatment of choice for CD. Untreated or improperly treated Cushing's disease
      leads to the development of serious complications, which lower patients' quality
      of life. Mortality in this group is high, reaching 50% within a 5-year follow-up
      period. In this study, we present our own experience and discuss the importance
      of preoperative hormone measurements, magnetic resonance imaging (MRI) of the
      pituitary, results of histopathological examination (immunohistochemical and
      ultrastructural in electron microscopy) and postoperative early and late hormonal
      assessment in the aspect of TSS efficacy. The performed analysis is based on the
      current criteria for remission of Cushing's disease. Our study emphasises the
      need for long-term postoperative endocrinological follow-up, which facilitates
      early detection of recurrent hypercortisolemia.

PMID- 23115077
TI  - B-cell receptor configuration and adverse cytogenetics are associated with
      autoimmune hemolytic anemia in chronic lymphocytic leukemia.
AB  - The development of autoimmune hemolytic anemia (AIHA) in patients with chronic
      lymphocytic leukemia (CLL) is associated with specific biological features. The
      occurrence of AIHA was hereby investigated in a retrospective series of 585 CLL
      patients with available immunoglobulin heavy chain variable (IGHV) gene status.
      AIHA occurred in 73 patients and was significantly associated with an IGHV
      unmutated (UM) status (P < 0.0001) and unfavorable [del(17)(p13) and
      del(11)(q23)] cytogenetic lesions (P < 0.0001). Stereotyped HCDR3 sequences were
      identified in 29.6% of cases and were similarly represented among patients
      developing or not AIHA; notably, subset #3 was associated with a significantly
      higher risk of AIHA than the other patients (P = 0.004). Multivariate analysis
      showed that UM IGHV, del(17)(p13) and del(11)(q23), but not stereotyped subset
      #3, were the strongest independent variables associated with AIHA. Based on these
      findings, we generated a biological risk score for AIHA development according to
      the presence of none (low risk), one (intermediated risk), or two (high risk) of
      the independent risk factors. Overall, our data indicate that UM IGHV status
      and/or unfavorable cytogenetic lesions are associated with the risk of developing
      secondary AIHA in CLL patients and suggest a possible role of specific
      stereotyped B-cell receptor subsets in a proportion of cases.

PMID- 23115078
TI  - Decreased luteinizing hormone pulse frequency is associated with elevated 24-hour
      ghrelin after calorie restriction and exercise in premenopausal women.
AB  - Elevated ghrelin has been shown to be associated with reduced luteinizing hormone
      (LH) pulsatility in Rhesus monkeys, rats, men, and recently women. We previously
      reported that 24-h ghrelin concentrations are elevated in women following a 3-mo
      exercise and diet program leading to weight loss. We investigated whether the
      elevations in ghrelin following an ~3-mo exercise and diet program leading to
      weight loss are associated with a decrease in LH pulsatility. The nonexercising
      control group (Control, n = 5) consumed a controlled diet that matched energy
      needs, whereas energy intake in the exercise group (Energy Deficit, n = 16) was
      reduced from baseline energy requirements and supervised exercise training
      occurred five times per a week. Significant decreases in body weight (-3.0 +/-
      0.6 kg), body fat (-2.9 +/- 0.4 kg) and 24-h LH pulse frequency (-0.18 +/- 0.08
      pulses/h), and a significant increase in 24-h mean ghrelin were observed in only
      the Energy Deficit group. The pre-post change in LH pulse frequency was
      negatively correlated with the change in mean 24-h ghrelin (R = -0.485, P =
      0.030) and the change in peak ghrelin at lunch (R = -0.518, P = 0.019).
      Interestingly, pre-post change in night LH pulse frequency was negatively
      correlated with the change in mean day ghrelin (R = -0.704, P = 0.001). Elevated
      total ghrelin concentrations are associated with the suppression of LH
      pulsatility in premenopausal women and may play a role in the suppression of
      reproductive function following weight loss.

PMID- 23115079
TI  - Nitrogen in dietary glutamate is utilized exclusively for the synthesis of amino
      acids in the rat intestine.
AB  - Although previous studies have shown that virtually the entire carbon skeleton of
      dietary glutamate (glutamate-C) is metabolized in the gut for energy production
      and amino acid synthesis, little is known regarding the fate of dietary glutamate
      nitrogen (glutamate-N). In this study, we hypothesized that dietary glutamate-N
      is an effective nitrogen source for amino acid synthesis and investigated the
      fate of dietary glutamate-N using [(15)N]glutamate. Fischer male rats were given
      hourly meals containing [U-(13)C]- or [(15)N]glutamate. The concentration and
      isotopic enrichment of several amino acids were measured after 0-9 h of feeding,
      and the net release of each amino acid into the portal vein was calculated. Most
      of the dietary glutamate-C was metabolized into CO(2), lactate, or alanine (56,
      13, and 12% of the dietary input, respectively) in the portal drained viscera
      (PDV). Most of the glutamate-N was utilized for the synthesis of other amino
      acids such as alanine and citrulline (75 and 3% of dietary input, respectively)
      in the PDV, and only minor amounts were released into the portal vein in the form
      of ammonia and glutamate (2 and 3% of the dietary input, respectively).
      Substantial incorporation of (15)N into systemic amino acids such as alanine,
      glutamine, and proline, amino acids of the urea cycle, and branched-chain amino
      acids was also evident. These results provide quantitative evidence that dietary
      glutamate-N distributes extensively to amino acids synthesized in the PDV and,
      consequently, to circulating amino acids.

PMID- 23115080
TI  - Muscle protein synthesis, mTORC1/MAPK/Hippo signaling, and capillary density are
      altered by blocking of myostatin and activins.
AB  - Loss of muscle mass and function occurs in various diseases. Myostatin blocking
      can attenuate muscle loss, but downstream signaling is not well known. Therefore,
      to elucidate associated signaling pathways, we used the soluble activin receptor
      IIb (sActRIIB-Fc) to block myostatin and activins in mice. Within 2 wk, the
      treatment rapidly increased muscle size as expected but decreased capillary
      density per area. sActRIIB-Fc increased muscle protein synthesis 1-2 days after
      the treatment correlating with enhanced mTORC1 signaling (phosphorylated rpS6 and
      S6K1, r = 0.8). Concurrently, increased REDD1 and eIF2Bepsilon protein contents
      and phosphorylation of 4E-BP1 and AMPK was observed. In contrast, proangiogenic
      MAPK signaling and VEGF-A protein decreased. Hippo signaling has been
      characterized recently as a regulator of organ size and an important regulator of
      myogenesis in vitro. The phosphorylation of YAP (Yes-associated protein), a
      readout of activated Hippo signaling, increased after short- and longer-term
      myostatin and activin blocking and in exercised muscle. Moreover, dystrophic mdx
      mice had elevated phosphorylated and especially total YAP protein content. These
      results show that the blocking of myostatin and activins induce rapid skeletal
      muscle growth. This is associated with increased protein synthesis and mTORC1
      signaling but decreased capillary density and proangiogenic signaling. It is also
      shown for the first time that Hippo signaling is activated in skeletal muscle
      after myostatin blocking and exercise and also in dystrophic muscle. This
      suggests that Hippo signaling may have a role in skeletal muscle in various
      circumstances.

PMID- 23115081
TI  - CXCL17, an orphan chemokine, acts as a novel angiogenic and anti-inflammatory
      factor.
AB  - Chemokines play pivotal roles in the recruitment of various immune cells to
      diverse tissues in both physiological and pathological conditions. CXCL17 is an
      orphan chemokine preliminarily found to be involved in tumor angiogenesis.
      However, its protein nature, as well as its endogenous bioactivity, has not been
      well clarified. Using real-time PCR, immunohistochemical staining, and Western
      blotting, we found that CXCL17 is highly expressed in both a constitutive and
      inducible manner in the rat gastric mucosa, where it undergoes endoproteolysis
      during protein maturation. The mature CXCL17 exhibited strong chemoattractant
      abilities targeting monocytes and macrophages, potentially through ERK1/2 and p38
      but not JNK signaling. CXCL17 also induced the production of proangiogenic
      factors such as vascular endothelial growth factor A from treated monocytes.
      Furthermore, in contrast to other CXC chemokines that accelerate inflammatory
      responses, CXCL17 showed novel anti-inflammatory effects on LPS-activated
      macrophages. Therefore, our data suggest that CXCL17 in the gastric lamina
      propria may play an important role in tissue repair and anti-inflammation, both
      of which help to maintain the integrity of the gastric mucosa.

PMID- 23115082
TI  - Glucose metabolism is altered after loss of L cells and alpha-cells but not
      influenced by loss of K cells.
AB  - The enteroendocrine K and L cells are responsible for secretion of glucose
      dependent insulinotropic polypeptide (GIP) and glucagon like-peptide 1 (GLP-1),
      whereas pancreatic alpha-cells are responsible for secretion of glucagon. In
      rodents and humans, dysregulation of the secretion of GIP, GLP-1, and glucagon is
      associated with impaired regulation of metabolism. This study evaluates the
      consequences of acute removal of Gip- or Gcg-expressing cells on glucose
      metabolism. Generation of the two diphtheria toxin receptor cellular knockout
      mice, TgN(GIP.DTR) and TgN(GCG.DTR), allowed us to study effects of acute
      ablation of K and L cells and alpha-cells. Diphtheria toxin administration
      reduced the expression of Gip and content of GIP in the proximal jejunum in
      TgN(GIP.DTR) and expression of Gcg and content of proglucagon-derived peptides in
      both proximal jejunum and terminal ileum as well as content of glucagon in
      pancreas in TgN(GCG.DTR) compared with wild-type mice. GIP response to oral
      glucose was attenuated following K cell loss, but oral and intraperitoneal
      glucose tolerances were unaffected. Intraperitoneal glucose tolerance was
      impaired following combined L cell and alpha-cell loss and normal following alpha
      cell loss. Oral glucose tolerance was improved following L cell and alpha-cell
      loss and supernormal following alpha-cell loss. We present two mouse models that
      allow studies of the effects of K cell or L cell and alpha-cell loss as well as
      isolated alpha-cell loss. Our findings show that intraperitoneal glucose
      tolerance is dependent on an intact L cell mass and underscore the diabetogenic
      effects of alpha-cell signaling. Furthermore, the results suggest that K cells
      are less involved in acute regulation of mouse glucose metabolism than L cells
      and alpha-cells.

PMID- 23115083
TI  - Sleep and Parkinson's disease: a review of case-control polysomnography studies.
AB  - The link between Parkinson's disease (PD) and certain primary sleep disorders has
      yet to be clarified. We performed a systematic review of case-control
      polysomnography studies to evaluate the relationship between PD and sleep
      disorders. A PubMed literature search and bibliography review yielded 15 case
      control polysomnography studies in patients with PD. Studies differed by
      recruitment methods, duration of polysomnography monitoring, and sleep parameters
      measured. Subjective sleepiness was greater in patients than controls (50%-66% vs
      2.9%-12%) despite lack of objective increase in daytime sleepiness by mean sleep
      latency testing. The 4 case-control polysomnography studies investigating rapid
      eye movement behavior disorder support a higher prevalence in PD (0%-47% vs 0%
      1.8% in controls), although differences in diagnostic criteria hamper
      interpretation. The preponderance of evidence did not support an increased
      incidence of obstructive sleep apnea (27%-60% vs 13%-65%) or periodic leg
      movements of sleep in patients compared to controls. Adequately powered,
      prospective studies with uniform methodology and healthy controls are needed to
      further address the association and pathophysiological significance between PD
      and sleep problems.

PMID- 23115084
TI  - Clinical significance of organic anion transporting polypeptides (OATPs) in drug
      disposition: their roles in hepatic clearance and intestinal absorption.
AB  - Organic anion transporting polypeptide (OATP) family transporters accept a number
      of drugs and are increasingly being recognized as important factors in governing
      drug and metabolite pharmacokinetics. OATP1B1 and OATP1B3 play an important role
      in hepatic drug uptake while OATP2B1 and OATP1A2 might be key players in
      intestinal absorption and transport across blood-brain barrier of drugs,
      respectively. To understand the importance of OATPs in the hepatic clearance of
      drugs, the rate-determining process for elimination should be considered; for
      some drugs, hepatic uptake clearance rather than metabolic intrinsic clearance is
      the more important determinant of hepatic clearances. The importance of the
      unbound concentration ratio (liver/blood), K(p,uu) , of drugs, which is partly
      governed by OATPs, is exemplified in interpreting the difference in the IC(50) of
      statins between the hepatocyte and microsome systems for the inhibition of HMG
      CoA reductase activity. The intrinsic activity and/or expression level of OATPs
      are affected by genetic polymorphisms and drug-drug interactions. Their effects
      on the elimination rate or intestinal absorption rate of drugs may sometimes
      depend on the substrate drug. This is partly because of the different
      contribution of OATP isoforms to clearance or intestinal absorption. When the
      contribution of the OATP-mediated pathway is substantial, the pharmacokinetics of
      substrate drugs should be greatly affected. This review describes the estimation
      of the contribution of OATP1B1 to the total hepatic uptake of drugs from the data
      of fold-increases in the plasma concentration of substrate drugs by the genetic
      polymorphism of this transporter. To understand the importance of the OATP family
      transporters, modeling and simulation with a physiologically based
      pharmacokinetic model are helpful.

PMID- 23115085
TI  - Effect of coadministration of single and multiple doses of rifampicin on the
      pharmacokinetics of fexofenadine enantiomers in healthy subjects.
AB  - The effect of rifampicin on the pharmacokinetics of fexofenadine enantiomers was
      examined in healthy subjects who received fexofenadine alone or with single or
      multiple doses of rifampicin (600 mg). A single coadministered dose of rifampicin
      significantly decreased the oral clearance (CL(tot)/F) and renal clearance
      (CL(r)) of S- and R-fexofenadine by 76 and 62%, and 73 and 62%, respectively.
      Even after multiple doses, rifampicin significantly decreased these parameters,
      although the effect on the CL(tot)/F was slightly blunted. Multiple doses of
      rifampicin abolished the difference in the CL(tot)/F of fexofenadine enantiomers,
      whereas the stereoselectivity in the CL(r) persisted. Rifampicin inhibited the
      uptake of fexofenadine enantiomers by human hepatocytes via organic anion
      transporter (OAT) OATP1B3 and its basal-to-apical transport in Caco-2 cells, but
      not OAT3-mediated or multidrug and toxic compound extrusion 1 (MATE1)-mediated
      transport. The plasma-unbound fraction of S-fexofenadine was 1.8 times higher
      than that of R-fexofenadine. The rifampicin-sensitive uptake by hepatocytes was
      1.6 times higher for R-fexofenadine, whereas the transport activities by OATP1B3,
      OAT3, MATE1, or P-glycoprotein were identical for both enantiomers. S
      fexofenadine is a more potent human histamine H1 receptor antagonist than R
      fexofenadine. In conclusion, rifampicin has multiple interaction sites with
      fexofenadine, all of which contribute to increasing the area under the curve of
      fexofenadine when they are given simultaneously, to surpass the effect of the
      induction of P-glycoprotein elicited by multiple doses.

PMID- 23115086
TI  - Effects of hypothermia on the disposition of morphine, midazolam, fentanyl, and
      propofol in intensive care unit patients.
AB  - Therapeutic hypothermia (TH) may induce pharmacokinetic changes that may affect
      the level of sedation. We have compared the disposition of morphine, midazolam,
      fentanyl, and propofol in TH with normothermia in man. Fourteen patients treated
      with TH following cardiac arrest (33-34 degrees C) were compared with eight
      matched critically ill patients (36-38 degrees C). Continuous infusions of
      morphine and midazolam were stopped and replaced with infusions of fentanyl and
      propofol to describe elimination and start of infusion pharmacokinetics,
      respectively. Serial serum and urine samples were collected for 6-8 hours for
      validated quantification and subsequent pharmacokinetic analysis. During TH,
      morphine elimination half-life (t(1/2)) was significantly higher, while total
      clearance (CL(tot)) was significantly lower (median [semi-interquartile range (s
      iqr)]): t(1/2), 266 (43) versus 168 (11) minutes, P < 0.01; CL(tot), 1201 (283)
      versus 1687 (200) ml/min, P < 0.01. No significant differences were seen for
      midazolam. CL(tot) of fentanyl and propofol was significantly lower in
      hypothermic patients [median (s-iqr)]: fentanyl, 726 (230) versus 1331 (678)
      ml/min, P < 0.05; propofol, 2046 (305) versus 2665 (223) ml/min, P < 0.05.
      Compared with the matched, normothermic intensive care unit patients, t(1/2) of
      morphine was significantly higher during TH. CL(tot) was lower during TH for
      morphine, fentanyl, and propofol but not for midazolam. Reducing the infusion
      rates of morphine, fentanyl, and propofol during TH is encouraged.

PMID- 23115087
TI  - Changes in the properties of normal human red blood cells during in vivo aging.
AB  - The changes in red blood cells (RBC) as they age and the mechanisms for their
      eventual removal have been of interest for many years. Proposed age-related
      changes include dehydration with increased density and decreased size, increased
      membrane IgG, loss of membrane phospholipid asymmetry, and decreased activity of
      KCl cotransport. The biotin RBC label allows unambiguous identification of older
      cells and exploration of their properties as they age. Autologous normal human
      RBC were labeled ex vivo and, after reinfusion, compared with unlabeled RBC
      throughout their lifespan. RBC density increased with age, with most of the
      change in the first weeks. Near the end of their lifespan, RBC had increased
      surface IgG. However, there was no evidence for elevated external
      phosphatidylserine (PS) even though older RBC had significantly lower activity of
      aminophospholipid translocase (APLT). KCl cotransport activity persisted well
      past the reticulocyte stage, but eventually decreased as the RBC became older.
      These studies place limitations on the use of density fractionation for the study
      of older human RBC, and do not support loss of phospholipid asymmetry as a
      mechanism for human RBC senescence. However, increased levels of IgG were
      associated with older RBC, and may contribute to their removal from the
      circulation.

PMID- 23115088
TI  - Ambulance services of lagos state, Nigeria: a six-year (2001-2006) audit.
AB  - BACKGROUND: Emergency medical care is designed to overcome the factors most
      commonly implicated in preventable mortality, such as delays in seeking care,
      access to health facility, and the provision of adequate care at the facility.
      The developed world has recognized the importance of organized emergency medical
      services and has well established systems. The Lagos State Government established
      the first emergency medical system in Nigeria in 2001. OBJECTIVE: This was to
      review the activities of the Lagos State Emergency Ambulance Services (LASAMBUS)
      within the stated period with the hope that our findings can be used to audit the
      system and make recommendations for further improvement. SUBJECTS, MATERIALS AND
      METHODS: We reviewed the records of the State Ministry of Health for the data on
      the activities of LASAMBUS from 2001-2006. The number and types of emergencies
      that were seen and managed with the associated morbidity and mortality were
      reviewed. The constraints that were encountered by the LASAMBUS staff were also
      studied. The data that was obtained was entered into a proforma designed for the
      study. Analysis of the data was done using the Microsoft Excel software. RESULTS:
      A total of 32,774 cases comprising 21,977(67.1%) males,10,797(32.9%) females and
      a male to female (M:F) ratio of 2.04:1, were seen during the study period. Trauma
      was responsible for 29,500 (90%) of the cases. No mortality was recorded during
      the transfer of the cases. The records of mortality for the LASAMBUS-transferred
      cases were not available. CONCLUSION/RECOMMENDATIONS: Trauma cases formed the
      majority of the cases that were seen with road traffic accident constituting a
      large proportion of these. Health education focusing on improving driving
      etiquette of Drivers and injury prevention should intensified. More equipped
      emergency centres should be established to reduce victims transit and
      injuryintervention time. Record keeping and documentations should be improved for
      better assessment of the activities.

PMID- 23115089
TI  - Beliefs and attitudes towards dementia among community leaders in northern
      Nigeria.
AB  - BACKGROUND: Dementia is an important devastating disease in old age. The number
      of dementia cases is in increasing worldwide with majority of them living in
      developing countries; however awareness about this important disease is poor
      especially in these developing countries. OBJECTIVES: This study aimed at
      determining the beliefs and attitude of community leaders on dementia in Northern
      Nigeria. METHODS: A cross sectional descriptive study was done using a structured
      questionnaire answered in Yes or No pattern. The questions were derived from the
      informant section of Community Screening Interview for Dementia and Blessed
      Dementia Scale. Fifty seven traditional rulers and fourty three Islamic clerics
      were interviewed. Data obtained was analysed using SPSS for windows version 11.0.
      RESULTS: The mean age of the participants was 57.76 +/- 11. 10 years and 28% were
      over the age off 65 years. The result showed that 77 (77%) of the subject
      believed that dementia is a normal process of aging. This was significantly
      associated with educational status but not age of the participants. The most
      recognisable symptoms are psychotic features of dementia (82%), while difficulty
      in dressing (56%) is the least recognisable symptom. Most of the participants
      would refer a person with features suggestive of dementia to see a physician.
      CONCLUSION: The study demonstrated that the belief dementia is a normal process
      ageing is common among these community leader. Therefore there is need to carry
      out awareness campaign to educate them.

PMID- 23115090
TI  - Cardiovascular epidemiological transition in a rural habitat of Nigeria: the case
      of mangu local government area.
AB  - BACKGROUND: Epidemiological transition is at various stages in different places.
      The true situation in sub-Saharan Africa (SSA) is largely unknown. Having studied
      this rural habitat 17 years ago, we returned there to study several
      cardiovascular disease (CVD) risk factors to see if any change had occurred.
      METHODS: The communities studied in 1991 as part of the national CVD survey were
      returned to in 2008 and re-studied descriptively in a cross-sectional manner. All
      adults 15 years and above, apart from demographic and personal data had blood
      pressure (BP) and some blood indices determined. RESULTS: Over the period, some
      changes occurred. The mean (SD) age increased from 34.1(16.9) to 45.5(18.2) years
      suggesting an ageing population. More people in 2008 than 1991 lived most of
      their last 5 years in the urban areas suggesting some influence of urbanisation.
      Significantly fewer people smoked and drank after 17 years. However mean (SD) of
      Body Mass Index rose [20.7(2.8) to 23.7(4.5) kg/m2], as well as SBP and DBP.
      Prevalence of hypertension rose from 7.4% to 20.9%. Both total and HDL
      cholesterol rose, although atherogenic index dropped. Mean (SD) blood sugar
      interestingly dropped from 5.0(2.9) to 4.6(1.0) mmol/l. CONCLUSION:
      Epidemiological transition is evident in this rural SSA habitat, and proactive
      steps to stem the tide and curb the consequences of CVD should be instituted.

PMID- 23115091
TI  - Nasogastric tube use in children after abdominal surgery- how long should it be
      kept in Situ?
AB  - BACKGROUND: Traditionally, the use of a nasogastric tube (NGT) after a laparotomy
      is said to prevent vomiting, aspiration, abdominal distension and paralytic
      ileus, which are likely to complicate the postoperative course. OBJECTIVE: To
      determine if discontinuation of NGT within 24 hours of abdominal surgical
      procedures in children has any effect on postoperative recovery. MATERIALS AND
      METHODS: We prospectively studied children who needed NGT passed for abdominal
      surgical procedures. NGTs were removed within 24 hours in all but 46 children who
      had the tube in situ for 3 to 5 days. Time to first and full oral feeds, length
      of hospital stay and complications were compared between the groups. RESULTS:
      Children who had their NGTs removed within 24 hours (N = 120, Group 1) were
      compared with those who had NGT in place for 3 to 5 days (N = 46, Group 2). The
      mean time to first oral sips was 1.02 +/- 0.13 days for Group 1 and 3.09 +/- 0.29
      days for Group 2 (p = 0.001). The mean time to full feeding was 2.22 +/- 0.54
      days for Group 1 and 4.54 +/- 0.55 days for Group 2 (p = 0.001). Mean length of
      hospital stay (LOHS) was 8.32 +/- 5.49 days for Group 1 and 12.78 +/- 8.79 days
      for Group 2 (p = 0.001). Mean LOHS was 9.55 +/- 6.85 days for both groups
      combined. Ten complications associated with the removal of the NGT occurred in
      both groups- 6 in Group 1 and 4 in Group 2 (p = 0.37). These were mainly vomiting
      and abdominal distension. CONCLUSION: Our findings suggest that routine use of
      NGTs for decompression after laparotomy may be safely dispensed with after the
      child has recovered from anaesthesia.

PMID- 23115092
TI  - Determinants of paediatrician's presence at Caesarian section.
AB  - BACKGROUND: Paediatricians are required to attend all Caesarian sections, yet
      most neonates so delivered do not require complex resuscitations necessitating a
      paediatrician's presence. METHODS: All Caesarean sections in the University of
      Benin Teaching Hospital from January to December 2009 were prospectively studied.
      The socio-demographic characteristics, indication and type of surgery, and the
      type of anaesthesia were recorded. Neonatal outcome was assessed with Apgar
      scores at 1 and 5 minutes and the need for a paediatrician determined. RESULTS:
      There were 431 cases of caesarean section within the period and 326 (75.6%) of
      these had antenatal care. About three-quarters of the patients had emergency
      caesarean section. Indications for caesarean section were foetal in 19% and
      maternal in 81%. Subarachnoid block was the main anaesthetic technique 392/431
      (91.0%). Apgar score in 1 min was less than 7 in 172/431 (39.9%) and was severe
      (< 4) in 26/ 431 (6.0%). Lack of ante natal care (p < 0.05, RR = 1.3, 95% CI =
      1.0 - 1.7 ), foetal indications (p < 0.05, RR = 1.4, 95% CI = 1.1 - 1.8),
      emergency caesarean section (p < 0.05, RR = 1.4, 95% C1 =1.0 -1.8), general
      anaesthesia (p = 0.0056, RR = 1.6, 95% CI = 1.2 -2.2) and active resuscitation (p
      < 0.05, RR = 2.5, 95% CI = 2.1 =3.1) were associated with Apgar scores less 7 in
      1 minute. CONCLUSION: Unbooked status, foetal indication (foetal distress,
      prematurity, abnormal lie), emergency sections, and general anaesthesia may lead
      to poor Apgar scores and the need for active resuscitation. These settings
      justify the paediatrician's presence at Caesarean section.

PMID- 23115093
TI  - Characteristics of inflammatory bowel disease in three tertiary health centers in
      southern Nigeria.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) refers to two chronic inflammatory
      disorders of the gastrointestinal tract which is generally believed to be rare in
      most African countries. The objectives of the current study were to present the
      experience of three tertiary gastroenterology centers in southern part of Nigeria
      on IBD, highlighting the age distribution of the patients seen, management and
      the impact on the quality of their life in university-based community-type
      practices in Nigeria. METHODS: This was a retrospective review of charts of
      inflammatory bowel disease seen between January 2007 and June 2010 at three
      teaching hospitals in Southern Nigeria. Diagnosis of IBD was made from clinical
      manifestations, colonoscopic and histopathological findings. RESULTS: During the
      study period, 12 patients presented with clinical features consistent with
      inflammatory bowel disease. There were 8 (66.7%) males and 4 (33.3%) females and
      had ages ranged from 18 years to 80 years with a median of 26.5 years. Eight
      (66.7%) patients had ulcerative colitis while 4(33.3%) had Crohn's disease. Ten
      (83.3%) patients had severe disease with main clinical features being recurrent
      diarrhoea and passage of mucoid bloody stools. All the patients had treatments
      with sulphasalazine or mesalazine, steroids and antibiotics with good responses.
      One patient died following the occurrence of toxic megacolon. CONCLUSION:
      Although IBD is uncommon in Nigeria, high index of suspicion is necessary by
      attending physicians managing patients with recurrent passage of mucoid bloody
      stools. Prompt gastroenterological referral and judicious use of colonoscopy and
      biopsy will assist in making the diagnosis.

PMID- 23115094
TI  - Trends in the use of female sterilisation through minilaparotomy for
      contraception at a teaching hospital in north central Nigeria.
AB  - BACKGROUND: Female sterilisation is the most widely used method of contraception
      worldwide. However, only a small proportion of contraceptors are reported to rely
      on female sterilisation in Nigeria. Continuous reviews of trends in its use are
      necessary to develop policies that will improve uptake in the country. OBJECTIVE:
      To determine the volume and trends in the use of female sterilisation through
      minilaparotomy as a method of contraception in a Nigerian university teaching
      hospital. METHODS: The records of women who had sterilisation through
      minilaparotomy over a ten year period were reviewed for socialdemographic
      characteristics, reasons for undergoing sterilisation, timing of the procedure,
      surgical method used and complications recorded. This is too sketchy RESULTS:
      Female sterilisation through minilaparotomy accounted for 95 (0.8%) of the 12,035
      total contraceptive use during the period. The rate decreased from 1.5% of total
      contraceptive use in 1995 to 0.22% in 2003. Eighty two (86.4%) of the female
      sterilisation acceptors were aged 35 years and above, 46 (48.4%) had no or only
      primary education and 42 (44.2%) were petty traders. Sixty six (69.5%) of the
      women were grandmultiparae and 70 (73.7%) had more children than they desired.
      Seventy three (76.8%) had used other contraceptive methods before sterilisation.
      The average cost of female sterilisation through minilaparotomy in our hospital
      was USD25 and this was significantly more than the cost of other contraceptives,
      and more than hospital charges for normal vaginal delivery. CONCLUSION: The
      proportion of contraceptive acceptors who rely on female sterilisation is low in
      our environment and has steadily declined over the years. The higher cost of the
      procedure as compared to other contraceptives appears to be the main barrier.
      Reduction or outright elimination of cost will probably act as incentive for
      women to choose female sterilisation as a method of contraception.

PMID- 23115095
TI  - Effect of health education on the riding habits of commercial motorcyclists in
      Uyo, southern Nigeria.
AB  - BACKGROUND: The increasing number of motorcyclists in Nigeria has led to a rise
      in poor road safety practices leading to increased rate of accidents. This study
      was conducted to implement and evaluate the effect of safety education on riding
      habits of motorcyclists in Uyo, Nigeria. METHODS: The intervention study was
      conducted among commercial motorcyclists in Uyo with controls from another town
      in Akwa Ibom State. Baseline information was collected from both groups on their
      riding habits. Motorcyclists in Uyo were educated on appropriate road safety
      practices. Data was collected from both groups three months later and analysed
      using the Statistical Package for Social Sciences version 11. RESULTS: A total of
      200 respondents participated in the study, 100 per group. At 3 months post
      intervention, those riding when tired reduced in the intervention group from 69%
      at baseline to 42% (p < 0.05), while in the control group it increased from 74%
      to 79%. Furthermore, those who rested during riding hours increased from 30% at
      baseline to 93% (p < 0.05) in the intervention group, while it reduced from 40%
      to 36% in the control group. Those riding within speed limit in the intervention
      group increased from 37.5% at baseline to 56.6% (p < 0.05), while in the control
      group, it remained the same. Use of psycho-active substances reduced in the
      intervention group, though the changes were not statistically significant at p <
      0.05. CONCLUSION: Safety education improved many riding habits of motorcyclists
      in the intervention group. Road safety education is recommended for all
      motorcyclists to ensure safer road use.

PMID- 23115096
TI  - Prevalence of occupational accidents/Injuries among health care workers in a
      federal medical centre in southern Nigeria.
AB  - BACKGROUND: Health care workers (HCWs) are prone to occupational accidents and
      injuries such as needle pricks in the course of their day to day activities in
      the health care setting. OBJECTIVE: To determine the prevalence of needle sticks
      and other occupational exposures among HCWs in a Nigerian tertiary hospital.
      METHODS: This was a descriptive cross sectional design involving all the doctors,
      and all laboratory workers and a selection of nurses. A structured, pre-tested,
      selfadministered questionnaire was the tool for data collection. RESULTS: A total
      of 167 HCWs made up of 47 (28.1%) doctors, 100 (59.9%) nurses and 20 (12.0%)
      laboratory workers were interviewed. Twenty-five (53.2%) doctors, 53 (53.0%)
      nurses and 10 (50.0%) laboratory workers making a total of 88 (52.7%) HCWs had
      had needle pricks, while 28 (59.6%) doctors, 53 (53.0%) nurses and 8 (40.0%)
      laboratory workers making a total of 89 (53.3%) have had blood splashes. A higher
      proportion of nurses 54 (54.0%) had cuts from drug ampoules than doctors (34.0%)
      while 16 (36.2%) doctors had glove perforation during surgery compared to nine
      (9.0%) nurses. Only 43 (25.7%) HCWs reported to the staff clinic after sustaining
      accidents/injuries. CONCLUSION: The prevalence of needle sticks and other
      occupational accidents/injuries among HCWs in the Federal Medical Centre, Asaba,
      Nigeria is high. There is also a high rate of non-reporting of these injuries to
      relevant authorities. All health facilities should have a written injection
      safety policy and a post-exposure protocol and HCWs should be continually
      educated on them.

PMID- 23115097
TI  - The conundrum of polytrauma on the jos plateau.
AB  - BACKGROUND: The leading cause of morbidity and mortality from the end of the
      first year of life to the forty fifth is trauma. This is true worldwide but
      especially so in our environment. In no other situation are the complexities of
      the management of trauma more manifest than in the context of polytrauma. For
      this we undertake to study the problem of polytrauma in Jos. AIMS AND OBJECTIVES:
      To determine the frequency and pattern of occurrence of poly trauma in Jos
      university teaching hospital. PATIENTS AND METHODS: Consecutive patients
      presenting with polytrauma to the casualty department were prospectively studied.
      Data regarding demographics and a detailed description of injuries were entered
      into a proforma and collated over a one-year period. RESULTS: A total of 131
      patients were studied. There were 103 males and 28 females giving a male to
      female ratio of 3.7:1. The ages ranged from 2 to 61 years with a mean of 28.4 +/-
      12.4 years. Road traffic accident was the most common aetiology in 113 (86.3%)
      patients, while falls 7 (5.3%), gunshots 5 (3.8%) and assaults 2 (1.6%) were
      observed. The most frequently encountered injuries were head, extremity and chest
      in 71.8%, 68.5% and 29.2% respectively. The combinations most frequently observed
      were head?extremity (43.5%), head?chest (17.6%) and chest?extremity (10.7%)
      injuries. Complications were observed in 20.6% while death occurred in 7.6%.
      CONCLUSION: Polytrauma occurs with sufficient frequency to warrant serious
      attention. As majority follow RTA, there is a need to intensify measures aimed at
      improving road safety. There is also a need to establish pre-hospital
      care?ambulance services. It is suggested that improved orthopaedic and
      neurosurgical care will lead to improved polytrauma care and most importantly,
      the establishment of dedicated trauma teams in tertiary institutions is proposed
      as a prelude to the establishment of regional trauma centers.

PMID- 23115098
TI  - Histopathological features of tumours of the orbit and Adnexia seen in Korle-Bu
      teaching Hospital Ghana.
AB  - BACKGROUND: Reports of histological types of orbital and adnexal tumours are few
      in the West African Sub-region and non-existent in Ghana. OBJECTIVE: This study
      was to determine and report the histological types of orbital and adnexal tumours
      seen in the eye unit in Korle-bu Teaching Hospital METHODS: This was a
      retrospective study of orbital and adnexal tumours in a referral orbit and
      oculoplastic clinic in a teaching hospital in Ghana. Biopsy specimen taken from
      the orbit, conjunctiva and eyelids of patients referred to the orbit and
      oculoplastic clinic of the eye unit between November 2005 and October 2009 were
      mailed to Royal Hallamshire Hospital Sheffield, UK for histological evaluation.
      Histology reports of these biopsy specimens were reviewed and analysed for types
      of tumours, frequency of occurrence, sex and age of patients. RESULTS: A total of
      190 histological specimen were taken. One hundred and four (54.7%) were malignant
      tumours, 53 (27.9%) benign tumours and 12 (6.3%) inflammatory lesions. Eighteen
      (9.5%) of biopsies taken were mostly degenerative conditions. CONCLUSION: Our
      findings show, as reported from other centres, that squamous cell carcinomas are
      the commonest cancers of the orbit and adnexia, while malignant melanomas account
      for only 3.8% of cancers.

PMID- 23115099
TI  - An affordable laparoscopic surgery trainer for trainees in poor resource
      settings.
AB  - BACKGROUND: Laparoscopic surgery requires acquisition of new skills such as hand
      eye coordination of instruments whose working tips can only be seen in two
      dimensions on a monitor screen and depth perception. Simulators have been
      demonstrated as necessary to acquire these skills safely. However these
      simulators are expensive and not readily available in developing countries.
      METHODS: I describe a cheap homemade adaptation of a laparoscopic trainer using a
      polyethylene fluid container, a webcam and a laptop computer as a monitor. This
      simulator can be easily be assembled by any surgical resident for use in his
      private time. CONCLUSION: This simulator for laparoscopic surgery is cheap and
      can be readily assembled. A major limitation is the fixity of the camera which
      limits the working area to within ten to thirty centimeters of the camera. On the
      contrary the inability to alter the camera position eliminates the need for an
      assistant to hold the camera.

PMID- 23115100
TI  - Potassium-induced conversion of ventricular fibrillation after aortic declamping.
AB  - OBJECTIVES: The anti-fibrillatory effect of potassium is well recognized from
      experimental models. There have, however, been very few clinical reports on the
      use of potassium to convert ventricular fibrillation (VF) after cardioplegic
      arrest. METHODS: In total, 8465 adult patients undergoing cardiac operations on
      cardiopulmonary bypass (CPB) and with cold antegrade crystalloid cardioplegic
      arrest were consecutively enrolled in a database. Patients with VF after removal
      of the aortic clamp were given 20 mmol potassium, and if needed an extra 10 mmol,
      in the perfusion line and the conversion rate was registered. Preoperative and
      intraoperative factors possibly related to the occurrence of post-ischaemic VF
      were assessed. RESULTS: Of these, 1721 (20%) patients had VF and 1366 of these
      (79%) were successfully treated with potassium infusion. Only 355 (21%) patients
      (4% of all operations) had direct-current countershock. The need for pacing was
      lower in the treatment group compared with the non-treatment group (P <0.001).
      Multivariate analysis revealed as the main findings that age, gender, amount of
      cardioplegia related to body mass index (BMI), and blood transfusion during the
      time of CPB had a highly significant (P <0.001) impact on reducing the rate of
      post-arrest VF. Somewhat contrary to expectation, left ventricular hypertrophy
      (LVH) was not a significant factor (P = 0.32) for post-arrest VF. No conversion
      by potassium was significant for age (P <0.001), gender (P <0.001) and LVH (P
      <0.001), but not for blood transfusion during CPB (P = 0.38) and for the ratio of
      cardioplegia-BMI (P = 0.26). CONCLUSIONS: The results from this register study
      demonstrate that potassium infusion is an effective and convenient first-hand
      measure to convert post declamping VF on CPB.

PMID- 23115101
TI  - Total port-access lobectomy via a subcostal trans-diaphragmatic approach for lung
      cancer.
AB  - Video-assisted thoracic surgery has been recognized as an acceptable technique
      for the treatment of early-stage lung cancer, with the potential advantage of
      lower postoperative pain than that experienced after open thoracotomy. However,
      the procedure cannot completely alleviate postoperative pain and paraesthesia and
      causes some degree of intercostal nerve damage. To minimize postoperative pain in
      video-assisted thoracic surgery, several new approaches have recently been
      reported. We describe the case of a 51-year old woman who successfully underwent
      total port-access, video-assisted thoracoscopic lobectomy for Stage IA lung
      cancer via the subcostal trans-diaphragmatic approach. Our results demonstrate
      the feasibility and safety of this procedure, which offers the advantages of
      minimizing intercostal nerve damage and facilitating better handling of staplers.

PMID- 23115102
TI  - Does a gentamicin-impregnated collagen sponge reduce sternal wound infections in
      high-risk cardiac surgery patients?
AB  - OBJECTIVES: Sternal wound infections occurring after cardiac surgery have a
      critical impact on morbidity, mortality and hospital costs. This study evaluated
      the efficacy of a gentamicin-collagen sponge in decreasing deep sternal-wound
      infections in high-risk cardiac surgery patients. METHODS: We conducted a quasi
      experimental single-centre prospective cohort study in diabetic and/or overweight
      patients undergoing coronary-artery bypass surgery with bilateral internal
      mammary artery grafts. The end-point was the rate of reoperation for deep sternal
      wound infection. The period from January 2006 to October 2008, before the
      introduction of the gentamicin sponge, was compared with the period from November
      2008 to December 2010. RESULTS: Of 552 patients (median body mass index, 31.5;
      37.7% with diabetes requiring insulin), 68 (12.3%) had deep sternal wound
      infections. Reoperation for deep sternal wound infections occurred in 40/289
      (13.8%) preintervention patients and 22/175 (12.6%) patients managed with the
      sponge. Independent risk factors were female sex and longer time on mechanical
      ventilation, but not use of the sponge (adjusted odds ratio, 0.95; 95% confidence
      interval, 0.52-1.73; P = 0.88). The group managed with the sponge had a higher
      proportion of gentamicin-resistant micro-organisms (21/27, 77.8%) compared with
      the other patients (23/56, 41.1%; P < 0.01). The median time to reoperation for
      wound infection was higher with the sponge (21 vs 17 days, P < 0.01).
      CONCLUSIONS: A gentamicin-collagen sponge was not effective in preventing deep
      sternal wound infections in high-risk patients. Our results suggest that a
      substantial proportion of wound contaminations occur after bypass surgery with
      bilateral internal mammary artery grafts.

PMID- 23115103
TI  - Myoclonus and dystonia in cerebrotendinous xanthomatosis.
AB  - BACKGROUND: Cerebrotendinous xanthomatosis (CTX) is an inherited neurometabolic
      disorder. The main neurological manifestations of the disease are pyramidal
      syndrome, ataxia, peripheral neuropathy, cognitive impairment, epilepsy, and
      psychiatric disturbances. Myoclonic dystonia has been reported on in the setting
      of various neurometabolic diseases. Anecdotal reports describe movement disorders
      associated with CTX, but no dystonia with myoclonic events. METHODS: We collected
      clinical, biochemical, electrophysiological, neuroradiological, and genetic data
      of 6 patients with myoclonus and mild dystonia associated with CTX. From a
      systematic literature review, we analyzed 31 patients with movement disorders
      secondary to CTX. RESULTS: Our 6 patients presented distal myoclonus with mild
      dystonia of the upper limbs. Myoclonus was of subcortical origin, based on
      neurophysiological recordings, and differed from oromandibular myoclonus
      previously described in CTX patients. CONCLUSIONS: These results expand the
      phenotype of CTX and suggest that myoclonus and/or dystonia are underdiagnosed.
      In keeping with our findings, tremors previously observed in CTX patients might
      actually correspond to myoclonic events. We hypothesize that a dysfunction of the
      dentate nuclei-basal ganglia pathway may be involved.

PMID- 23115105
TI  - Consistent Gaussian basis sets of triple-zeta valence with polarization quality
      for solid-state calculations.
AB  - Consistent basis sets of triple-zeta valence with polarization quality for main
      group elements and transition metals from row one to three have been derived for
      periodic quantum-chemical solid-state calculations with the crystalline-orbital
      program CRYSTAL. They are based on the def2-TZVP basis sets developed for
      molecules by the Ahlrichs group. Orbital exponents and contraction coefficients
      have been modified and reoptimized, to provide robust and stable self-consistant
      field (SCF) convergence for a wide range of different compounds. We compare
      results on crystal structures, cohesive energies, and solid-state reaction
      enthalpies with the modified basis sets, denoted as pob-TZVP, with selected
      standard basis sets available from the CRYSTAL basis set database. The average
      deviation of calculated lattice parameters obtained with a selected density
      functional, the hybrid method PW1PW, from experimental reference is smaller with
      pob-TZVP than with standard basis sets, in particular for metallic systems. The
      effects of basis set expansion by diffuse and polarization functions were
      investigated for selected systems.

PMID- 23115104
TI  - Silibinin inhibits prostate cancer cells- and RANKL-induced osteoclastogenesis by
      targeting NFATc1, NF-kappaB, and AP-1 activation in RAW264.7 cells.
AB  - Currently, there are limited therapeutic options against bone metastatic prostate
      cancer (PCA), which is primarily responsible for high mortality and morbidity in
      PCA patients. Enhanced osteoclastogenesis is an essential feature associated with
      metastatic PCA in the bone microenvironment. Silibinin, an effective
      chemopreventive agent, is in phase II clinical trials in PCA patients but its
      efficacy against PCA cells-induced osteoclastogenesis is largely unknown.
      Accordingly, here we examined silibinin effect on PCA cells-induced
      osteoclastogenesis employing human PCA (PC3MM2, PC3, and C4-2B) and murine
      macrophage RAW264.7 cells. We also assessed silibinin effect on receptor
      activator of nuclear factor kappaB ligand (RANKL)-induced signaling associated
      with osteoclast differentiation in RAW264.7 cells. Further, we analyzed silibinin
      effect on osteomimicry biomarkers in PCA cells. Results revealed that silibinin
      (30-90 MUM) inhibits PCA cells-induced osteoclast activity and differentiation in
      RAW264.7 cells via modulating expression of several cytokines (IGF-1, TGF-beta,
      TNF-alpha, I-TAC, M-CSF, G-CSF, GM-CSF, etc.) that are important in
      osteoclastogenesis. Additionally, in RAW264.7 cells, silibinin decreased the
      RANKL-induced expression and nuclear localization of NFATc1, which is considered
      the master regulator of osteoclastogenesis. Furthermore, silibinin decreased the
      RANKL-induced DNA binding activity of NFATc1 and its regulators NF-kappaB and
      AP1, and the protein expression of osteoclast specific markers (TRAP, OSCAR, and
      cathepsin K). Importantly, silibinin also decreased the expression of
      osteomimicry biomarkers (RANKL, Runx2, osteocalcin, and PTHrP) in cell culture
      (PC3 and C4-2B cells) and/or in PC3 tumors. Together, our findings showing that
      silibinin inhibits PCA cells-induced osteoclastogenesis, suggest that silibinin
      could be useful clinically against bone metastatic PCA.

PMID- 23115106
TI  - FLT3 mutations in myelodysplastic syndrome and chronic myelomonocytic leukemia.
AB  - FMS-like tyrosine kinase III (FLT3) mutations occur in one-third of acute myeloid
      leukemia (AML) patients and predict poor outcome. The incidence and impact of
      FLT3 in myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML)
      is unknown. We conducted a retrospective review to identify WHO MDS and CMML
      patients with FLT3 mutations at diagnosis. A total of 2,119 patients with MDS and
      466 patients with CMML were evaluated at MD Anderson between 1997 and 2010. Of
      these, FLT3 mutation analysis was performed on 1,232 (58%) MDS and 302 (65%) CMML
      patients. FLT3 mutations were identified in 12 (0.95%) MDS patients: 9 (75%) had
      FLT3-ITD mutation and 3 had FLT3-tyrosine kinase domain (TKD) mutation. MDS
      patients with FLT3 mutations were younger (P = 0.02) and presented as RAEB (P =
      0.03) more frequently. Median overall survival (OS) for FLT3-mutated MDS patients
      was 19.0 months versus 16.4 months for FLT3-nonmutated MDS patients (P = 0.08).
      FLT3 mutations were identified in 13 (4.3%) CMML patients: 8 had FLT3-ITD
      mutation and 5 had FLT3-TKD mutation. There were no significant differences in
      demographic and disease characteristics among CMML patients with and without FLT3
      mutations. Median OS for FLT3-mutated CMML patients was 10.8 months versus 21.3
      months for FLT3-nonmutated CMML patients (P = 0.12). FLT3 occurs in MDS and CMML
      at a lower frequency than AML and does not predict poor outcome.

PMID- 23115107
TI  - Nutritional composition of actual and potential insect prey for the Kasekela
      chimpanzees of Gombe National Park, Tanzania.
AB  - Humans, all great ape species, and some lesser apes consume insects. Insects can
      provide comparable nutritional yields to meat on a gram-for-gram basis and may
      serve as an important source of energy, fat, protein, minerals, and vitamins for
      hominoids. Although potential insect prey are abundant in ape habitats, patterns
      of insectivory are not consistent across species or populations. Efforts to
      understand these patterns are complicated by a lack of nutritional data. We
      collected samples of insects consumed by the Kasekela chimpanzee community of
      Gombe National Park, Tanzania, as well as of some insects found within the
      community range and ignored by these chimpanzees but known to be preyed upon by
      Pan elsewhere. We determined the gross energy (GE), estimated metabolizable
      energy (ME), fat, protein, fiber, and ash content of these samples following
      standard methodologies. We use these data to test the hypothesis that Kasekela
      chimpanzees choose insect prey (at least in part) based on energy and/or
      macronutrient content. On a fresh-weight, per-gram basis, the insect prey
      consumed by Kasekela chimpanzees had significantly higher fat and lower ash
      content than other assayed insects, and on a fresh-weight, per-foraging-unit
      ("per-insect," "per-dip," or "per-nest") basis were significantly higher in GE,
      fat, and protein. On a per-gram basis, the assayed insects were generally
      comparable in energy and macronutrients to wild vertebrate meat. We conclude that
      Kasekela chimpanzees do favor insects that are high in energy, fat, and protein,
      and that the potential macronutrient yields from some forms of insectivory are
      not trivial.

PMID- 23115109
TI  - An economic prediction of refinement coefficients in wavelet-based adaptive
      methods for electron structure calculations.
AB  - The wave function of a many electron system contains inhomogeneously distributed
      spatial details, which allows to reduce the number of fine detail wavelets in
      multiresolution analysis approximations. Finding a method for decimating the
      unnecessary basis functions plays an essential role in avoiding an exponential
      increase of computational demand in wavelet-based calculations. We describe an
      effective prediction algorithm for the next resolution level wavelet
      coefficients, based on the approximate wave function expanded up to a given
      level. The prediction results in a reasonable approximation of the wave function
      and allows to sort out the unnecessary wavelets with a great reliability.

PMID- 23115108
TI  - Hospital use, associated costs, and payer status for infants born with spina
      bifida.
AB  - BACKGROUND: Health care use and costs for children with spina bifida (SB) are
      significantly greater than those of unaffected children. Little is known about
      hospital use and costs across health insurance payer types. We examined
      hospitalizations and associated costs by sociodemographic characteristics and
      payer type during the first year of life among children with SB. We also examined
      changes in health insurance payer status. METHODS: This study was a
      retrospective, statewide population-based analysis of infants with SB without
      anencephaly born in Florida during 1998-2007. Infants were identified by the
      Florida Birth Defects Registry and linked to hospital discharge records.
      Descriptive statistics on number of hospitalizations, length of stay, and
      estimated hospital costs per hospitalization and per infant were calculated
      during the first year of life. Results were stratified by selected
      sociodemographic variables and health insurance payer type. RESULTS: Among 615
      infants with SB, mean and median numbers of hospitalizations per infant were 2.4
      and 2.0, respectively. Mean and median total days of hospitalization per infant
      were 25.2 and 14.0 days, respectively. Approximately 18% of infants were
      hospitalized more than three times. Among infants with multiple hospitalizations,
      16.7% had a mix of public and private health insurance payers. Almost 60% of
      hospitalizations for infants were paid by public payer sources. Mean and median
      estimated hospital costs per infant were $39,059 and $21,937, respectively.
      CONCLUSIONS: Results suggest a small percentage of infants with SB have multiple
      hospitalizations with high costs. Further analysis on factors associated with
      length of stay, hospitalizations, and costs is warranted.

PMID- 23115110
TI  - Brief communication: new Y-chromosome binary markers improve phylogenetic
      resolution within haplogroup R1a1.
AB  - Haplogroup R1a1-M198 is a major clade of Y chromosomal haplogroups which is
      distributed all across Eurasia. To this date, many efforts have been made to
      identify large SNP-based subgroups and migration patterns of this haplogroup. The
      origin and spread of R1a1 chromosomes in Eurasia has, however, remained unknown
      due to the lack of downstream SNPs within the R1a1 haplogroup. Since the
      discovery of R1a1-M458, this is the first scientific attempt to divide haplogroup
      R1a1-M198 into multiple SNP-based sub-haplogroups. We have genotyped 217 R1a1
      M198 samples from seven different population groups at M458, as well as the Z280
      and Z93 SNPs recently identified from the "1000 Genomes Project". The two
      additional binary markers present an effective tool because now more than 98% of
      the samples analyzed assign to one of the three sub-haplogroups. R1a1-M458 and
      R1a1-Z280 were typical for the Hungarian population groups, whereas R1a1-Z93 was
      typical for Malaysian Indians and the Hungarian Roma. Inner and Central Asia is
      an overlap zone for the R1a1-Z280 and R1a1-Z93 lineages. This pattern implies
      that an early differentiation zone of R1a1-M198 conceivably occurred somewhere
      within the Eurasian Steppes or the Middle East and Caucasus region as they lie
      between South Asia and Eastern Europe. The detection of the Z93 paternal genetic
      imprint in the Hungarian Roma gene pool is consistent with South Asian ancestry
      and amends the view that H1a-M82 is their only discernible paternal lineage of
      Indian heritage.

PMID- 23115111
TI  - In vitro emergence of rifampicin resistance in Propionibacterium acnes and
      molecular characterization of mutations in the rpoB gene.
AB  - OBJECTIVES: Activity of rifampicin against Propionibacterium acnes biofilms was
      recently demonstrated, but rifampicin resistance has not yet been described in
      this organism. We investigated the in vitro emergence of rifampicin resistance in
      P. acnes and characterized its molecular background. METHODS: P. acnes ATCC 11827
      was used (MIC 0.007 mg/L). The mutation rate was determined by inoculation of
      10(9) cfu of P. acnes on rifampicin-containing agar plates incubated
      anaerobically for 7 days. Progressive emergence of resistance was studied by
      serial exposure to increasing concentrations of rifampicin in 72 h cycles using a
      low (10(6) cfu/mL) and high (10(8) cfu/mL) inoculum. The stability of resistance
      was determined after three subcultures of rifampicin-resistant isolates on
      rifampicin-free agar. For resistant mutants, the whole rpoB gene was amplified,
      sequenced and compared with a P. acnes reference sequence (NC006085). RESULTS: P.
      acnes growth was observed on rifampicin-containing plates with mutation rates of
      2 +/- 1 cfu  *  10(-9) (4096* MIC) and 12 +/- 5 cfu  *  10(-9) (4 * MIC). High
      level rifampicin resistance emerged progressively after 4 (high inoculum) and 13
      (low inoculum) cycles. In rifampicin-resistant isolates, the MIC remained >32
      mg/L after three subcultures. Mutations were detected in clusters I (amino acids
      418-444) and II (amino acids 471-486) of the rpoB gene after sequence alignment
      with a Staphylococcus aureus reference sequence (CAA45512). The five following
      substitutions were found: His-437 -> Tyr, Ser-442 -> Leu, Leu-444 -> Ser, Ile-483
      -> Val and Ser-485 -> Leu. CONCLUSION: The rifampicin MIC increased from highly
      susceptible to highly resistant values. The resistance remained stable and was
      associated with mutations in the rpoB gene. To our knowledge, this is the first
      report of the emergence of rifampicin resistance in P. acnes.

PMID- 23115112
TI  - Topography of dyskinesias and torticollis evoked by inhibition of substantia
      nigra pars reticulata.
AB  - GABAergic neurons of the substantia nigra pars reticulata (SNpr) and globus
      pallidus pars interna (GPi) constitute the output pathways of the basal ganglia.
      In monkeys, choreiform limb dyskinesias have been described after inhibition of
      the GPi, but not the SNpr. Given the anatomical and functional similarities
      between these structures, we hypothesized that choreiform dyskinesias could be
      evoked by inhibition of an appropriate region within the SNpr. The GABAA receptor
      agonist, muscimol, was infused into various sites within the SNpr and the
      adjacent STN of freely moving macaques. The effect of the GABAA antagonist,
      bicuculline (BIC), was also examined. Muscimol (MUS) in SNpr evoked the
      following: (1) choreiform dyskinesias of the contralateral arm and/or leg from
      central and lateral sites; (2) contralaterally directed torticollis from central
      and posterior sites; and (3) contraversive quadrupedal rotation from anterior and
      lateral sites. MUS infusions into the adjacent SN pars compacta or STN were
      without effect, ruling out a contribution of drug spread to adjacent structures.
      BIC in SNpr induced ipsiversive postures without choreiform dyskinesia or
      torticollis, whereas in the STN, it evoked ballistic movements. This is the first
      report of choreiform dyskinesia evoked by inhibition of the SNpr. This highly
      site-specific effect was obtained from a restricted region within the SNpr
      distinct from that responsible for inducing torticollis. These results suggest
      that overactivity of different SNpr outputs mediates choreiform dyskinesia and
      torticollis. These abnormalities are symptoms of dystonia, Huntington's disease,
      and iatrogenic dyskinesias, suggesting that these conditions may result, in part,
      from a loss of function in SNpr efferent projections.

PMID- 23115113
TI  - High-dose glucocorticoids plus Ofatumumab in fludarabine/alemtuzumab-resistant B
      cell chronic lymphocytic leukemia.

PMID- 23115114
TI  - BCL3 gene role in facial morphology.
AB  - BACKGROUND: Cleft lip (CL) with or without palate (CLP) and isolated cleft palate
      (CP) are etiologically complex diseases with interactions among various
      environmental and genetic factors. The aim of the current study was to identify
      association with genetic markers and phenotypic craniofacial data in patients
      with CL/CLP/CP parents. METHODS: Posteroanterior and lateral digital radiographs
      of the cranium were obtained from 74 parents of patients with CL/CLP/CP. One
      hundred seventy-three patients with CL/CLP/CP and 190 controls were enrolled in
      the study for the association test. Five genetic markers of the IRF6 gene and 14
      markers of the 19q13 locus were genotyped. Linear regression analysis was
      performed for the relationship of cephalometric measurements with genotype data
      adjusted for age, gender, and cleft type. Chi-square and transmission
      disequilibrium tests were performed to evaluate differences in alleles of the
      BCL3 gene. Positive findings were replicated in an independent sample (n = 95) of
      patients with CL/CLP/CP parents. RESULTS: Genetic markers of the BCL3 gene at
      19q13, rs7257231, and rs1979377 in the familial association test and rs10401176
      in the case-control association test, were associated with craniofacial
      phenotype. Carriers of BCL3 allele rs7257231T had longer posterior cranial bases
      than noncarriers (p(adjusted) = 0.0028), and in the familial-based association
      test showed the statistically strongest relationship (p(adjusted) = 0.05) to
      phenotype. Relation of rs7257231 to facial formation was confirmed in the
      replication group (p = 0.0024). CONCLUSIONS: The results indicate that BCL3,
      which has functions related to cell adhesion and whose downregulation can cause
      disruption of ectodermal development, is likely to be important in facial
      formation. Birth Defects Research (Part A), 2012.

PMID- 23115115
TI  - Rate coefficients of the CF3CHFCF3 + H -> CF3CFCF3 + H2 reaction at different
      temperatures calculated by transition state theory with ab initio and DFT
      reaction paths.
AB  - The minimum energy path (MEP) of the reaction, CF(3)CHFCF(3) + H -> transition
      state (TS) -> CF(3)CFCF(3) + H(2), has been computed at different ab initio
      levels and with density functional theory (DFT) using different functionals. The
      computed B3LYP/6-31++G**, BH&HLYP/cc-pVDZ, BMK/6-31++G**, M05/6-31+G**, M05-2X/6
      31+G**, UMP2/6-31++G**, PUMP2/6-31++G**//UMP2/6-31++G**, RCCSD(T)/aug-cc
      pVDZ//UMP2/6-31++G**, RCCSD(T)/aug-cc-pVTZ(spd,sp)//UMP2//6-31++G**,
      RCCSD(T)/CBS//M05/6-31+G**, and RCCSD(T)/CBS//UMP2/6-31++G** MEPs, and associated
      gradients and Hessians, were used in reaction rate coefficient calculations based
      on the transition state theory (TST). Reaction rate coefficients were computed
      between 300 and 1500 K at various levels of TST, which include conventional TST,
      canonical variational TST (CVT) and improved CVT (ICVT), and with different
      tunneling corrections, namely, Wigner, zero-curvature, and small-curvature (SCT).
      The computed rate coefficients obtained at different ab initio, DFT and TST
      levels are compared with experimental values available in the 1000-1200 K
      temperature range. Based on the rate coefficients computed at the ICVT/SCT level,
      the highest TST level used in this study, the BH&HLYP functional performs best
      among all the functionals used, while the RCCSD(T)/CBS//MP2/6-31++G** level is
      the best among all the ab initio levels used. Comparing computed reaction rate
      coefficients obtained at different levels of theory shows that, the computed
      barrier height has the strongest effect on the computed reaction rate
      coefficients as expected. Variational effects on the computed rate coefficients
      are found to be negligibly small. Although tunneling effects are relatively small
      at high temperatures (~1500 K), SCT corrections are significant at low
      temperatures (~300 K), and both barrier heights and the magnitudes of the
      imaginary frequencies affect SCT corrections.

PMID- 23115116
TI  - DYT7 gene locus for cervical dystonia on chromosome 18p is questionable.
AB  - BACKGROUND: A locus implicated in autosomal dominant cervical dystonia was
      assigned to chromosome 18p in 1 large family more than 15 years ago. This locus
      was designated DYT7. We reanalyzed the family clinically and genetically.
      METHODS: Clinical reevaluation of all family members was performed. There was
      Sanger sequencing of candidate genes, SNP array analysis, and exome sequencing in
      definitely affected family members. RESULTS: Diagnosis of cervical dystonia was
      definite in 6 family members and possible in 12. Analysis of candidate genes in
      18p revealed no alteration in definitely affected patients. There was no disease
      causing copy number variant in 18p. No potentially disease-causing mutations were
      detected in 18p by exome sequencing. The CIZ1 gene, mutated in some cases of
      cervical dystonia, was excluded. CONCLUSIONS: Location of DYT7 on 18p in
      autosomal dominant cervical dystonia is questionable. We demonstrate genetic
      heterogeneity of this form of dystonia.

PMID- 23115117
TI  - An extreme example of focal bone marrow involvement in acute myeloid leukemia.

PMID- 23115118
TI  - Phase composition control of calcium phosphate nanoparticles for tunable drug
      delivery kinetics and treatment of osteomyelitis. I. Preparation and drug
      release.
AB  - Developed in this study is a multifunctional material for simultaneous
      osseoinduction and drug delivery, potentially applicable in the treatment of
      osteomyelitis. It is composed of agglomerates of nanoparticles of calcium
      phosphate (CAP) with different monophasic contents. The drug-loading capacity and
      the release kinetics were investigated on two model drug compounds with different
      chemical structures, sizes, and adsorption propensities: bovine serum albumin and
      fluorescein. Loading of CAP powders with small molecule drugs was achieved by
      physisorption and desiccation-induced agglomeration of nanoparticulate subunits
      into microscopic blocks. The material dissolution rate and the drug release rate
      depended on the nature of the CAP phase, decreasing from monocalcium phosphate to
      monetite to amorphous CAP and calcium pyrophosphate to hydroxyapatite. The
      sustained release of the two model drugs was shown to be directly relatable to
      the degradation rate of CAP carriers. It was demonstrated that the degradation
      rate of the carrier and the drug release kinetics could be made tunable within
      the time scale of 1-2 h for the most soluble CAP phase, monocalcium phosphate, to
      1-2 years for the least soluble one, hydroxyapatite. From the standpoint of
      antibiotic therapy for osteomyelitis, typically lasting for 6 weeks, the most
      prospective CAP powder was amorphous CAP with its release time scale for a small
      organic molecule, the same category to which antibiotics belong, of 1-2 months
      under the conditions applied in our experiments. By combining these different CAP
      phases in various proportions, drug release profiles could be tailored to the
      therapeutic occasion.

PMID- 23115119
TI  - STAAR: statistical analysis of aromatic rings.
AB  - The statistical analysis of aromatic rings program allows for an automated search
      for anion-pi interactions between phenylalanine residues and carboxylic acid
      moieties of neighboring aspartic acid or glutamic acid residues in protein data
      bank (PDB) structures. The program is written in C++ and is available both as a
      standalone code and through a web implementation that allows users to upload and
      analyze biomolecular structures in PDB format. The program outputs lists of
      Phe/Glu or Phe/Asp pairs involved in potential anion-pi interactions, together
      with geometrical (distance and angle between the Phe's center of mass and Glu or
      Asp's center of charge) and energetic (quantum mechanical Kitaura-Morokuma
      interaction energy between the residues) descriptions of each anion-pi
      interaction. Application of the program on the latest content of the PDB shows
      that anion-pi interactions are present in thousands of protein structures and can
      possess strong energies, as low as -8.72 kcal/mol.

PMID- 23115120
TI  - Greater insulin-mediated Akt phosphorylation concomitant with heterogeneous
      effects on phosphorylation of Akt substrates in soleus of calorie-restricted
      rats.
AB  - Akt is a serine/threonine kinase that plays a key role in numerous cellular
      functions including metabolism, growth, protein synthesis, apoptosis, and cell
      proliferation. The most consistent and robust effect of moderate calorie
      restriction (CR; ~60% of ad libitum, AL, food consumption) on insulin signaling
      in rodent muscle has been enhanced insulin-induced phosphorylation of Akt (pAkt).
      However, there is limited knowledge regarding the mechanism for this enhancement
      and its consequences in predominantly slow-twitch muscle. Accordingly, in soleus
      muscle of 9-mo-old rats, we analyzed the effect of CR and insulin on important
      signaling events that are proximal to Akt activation including:
      pIR(Tyr1162/1163), pIRS1(Tyr), pIRS1(Ser312), IRS1-associated
      phosphatidylinositol 3-kinase activity, or pPTEN(Ser380). In addition, we
      analyzed the effect of CR and insulin on Akt substrates that have established or
      putative roles in glucose metabolism, cellular growth, maintenance of muscle
      structure, or protein synthesis including pGSK3alpha(Ser21), pGSK3beta(Ser9),
      pTSC2(Ser939), pP70S6K(Thr412), pAS160(Thr642), and pFLNc(Ser2213). The current
      study demonstrated that the CR-induced increase in pAkt in isolated soleus
      muscles from 9-mo-old rats can occur without concomitant enhancement of several
      important insulin signaling events that are proximal to Akt activation. These
      results suggest that the greater pAkt in the soleus muscles from CR rats was
      attributable to an alternative mechanism. We also observed that the effects of CR
      were not uniform for phosphorylation of six insulin-regulated Akt substrates in
      the soleus. The differential response in phosphorylation by Akt substrates likely
      has important implications for explaining the complex effect of CR diverse
      cellular functions.

PMID- 23115121
TI  - Alterations in activity and energy expenditure contribute to lean phenotype in
      Fischer 344 rats lacking the cholecystokinin-1 receptor gene.
AB  - CCK is hypothesized to inhibit meal size by acting at CCK1 receptors (CCK1R) on
      vagal afferent neurons that innervate the gastrointestinal tract and project to
      the hindbrain. Earlier studies have shown that obese Otsuka Long-Evans Tokushima
      Fatty (OLETF) rats, which carry a spontaneous null mutation of the CCK1R, are
      hyperphagic and obese. Recent findings show that rats with CCK1R-null gene on a
      Fischer 344 background (Cck1r(-/-)) are lean and normophagic. In this study, the
      metabolic phenotype of this rat strain was further characterized. As expected,
      the CCK1R antagonist, devazepide, failed to stimulate food intake in the Cck1r(-/
      ) rats. Both Cck1r(+/+) and Cck1r(-/-) rats became diet-induced obese (DIO) when
      maintained on a high-fat diet relative to chow-fed controls. Cck1r(-/-) rats
      consumed larger meals than controls during the dark cycle and smaller meals
      during the light cycle. These effects were accompanied by increased food intake,
      total spontaneous activity, and energy expenditure during the dark cycle and an
      apparent reduction in respiratory quotient during the light cycle. To assess
      whether enhanced responsiveness to anorexigenic factors may contribute to the
      lean phenotype, we examined the effects of melanotan II (MTII) on food intake and
      body weight. We found an enhanced effect of MTII in Cck1r(-/-) rats to suppress
      food intake and body weight following both central and peripheral administration.
      These results suggest that the lean phenotype is potentially driven by increases
      in total spontaneous activity and energy expenditure.

PMID- 23115122
TI  - Phycocyanin and phycocyanobilin from Spirulina platensis protect against diabetic
      nephropathy by inhibiting oxidative stress.
AB  - We and other investigators have reported that bilirubin and its precursor
      biliverdin may have beneficial effects on diabetic vascular complications,
      including nephropathy, via its antioxidant effects. Here, we investigated whether
      phycocyanin derived from Spirulina platensis, a blue-green algae, and its
      chromophore phycocyanobilin, which has a chemical structure similar to that of
      biliverdin, protect against oxidative stress and renal dysfunction in db/db mice,
      a rodent model for Type 2 diabetes. Oral administration of phycocyanin (300
      mg/kg) for 10 wk protected against albuminuria and renal mesangial expansion in
      db/db mice, and normalized tumor growth factor-beta and fibronectin expression.
      Phycocyanin also normalized urinary and renal oxidative stress markers and the
      expression of NAD(P)H oxidase components. Similar antioxidant effects were
      observed following oral administration of phycocyanobilin (15 mg/kg) for 2 wk.
      Phycocyanobilin, bilirubin, and biliverdin also inhibited NADPH dependent
      superoxide production in cultured renal mesangial cells. In conclusion, oral
      administration of phycocyanin and phycocyanobilin may offer a novel and feasible
      therapeutic approach for preventing diabetic nephropathy.

PMID- 23115123
TI  - Functional and biochemical characterization of soleus muscle in Down syndrome
      mice: insight into the muscle dysfunction seen in the human condition.
AB  - Persons with Down syndrome (DS) exhibit low muscle strength that significantly
      impairs their physical functioning. The Ts65Dn mouse model of DS also exhibits
      muscle weakness in vivo and may be a useful model to examine DS-associated muscle
      dysfunction. Therefore, the purpose of this experiment was to directly assess
      skeletal muscle function in the Ts65Dn mouse and to reveal potential mechanisms
      of DS-associated muscle weakness. Soleus muscles were harvested from anesthetized
      male Ts65Dn and wild-type (WT) colony controls. In vitro muscle contractile
      experiments revealed normal force generation of nonfatigued Ts65Dn soleus, but a
      12% reduction in force was observed during recovery from fatiguing contractions
      compared with WT muscle (P < 0.05). Indicators of oxidative stress and
      mitochondrial oxidative capacity were assessed to reveal potential mechanisms of
      DS-associated muscle weakness. Protein expression of copper-zinc superoxide
      dismutase (SOD1), a triplicated gene in persons with DS and Ts65Dn mice, was
      increased 25% (P < 0.05) in Ts65Dn soleus. Nontriplicated antioxidant protein
      expression was similar between groups. Lipid peroxidation was unaltered in Ts65Dn
      animals, but protein oxidation was 20% greater compared with controls (P < 0.05).
      Cytochrome-c oxidase expression was 22% lower in Ts65Dn muscle (P < 0.05), while
      expression of citrate synthase was similar between groups. Microarray analysis
      revealed alteration of numerous pathways in Ts65Dn muscle, including proteolysis,
      glucose and fat metabolism, neuromuscular transmission, and ATP biosynthesis. In
      summary, despite biochemical and gene expression differences in soleus muscle of
      Ts65Dn animals, the functional properties of skeletal muscle likely contribute a
      minor part to the in vivo muscle weakness.

PMID- 23115124
TI  - Cardiomyocyte-specific deletion of leptin receptors causes lethal heart failure
      in Cre-recombinase-mediated cardiotoxicity.
AB  - Although disruption of leptin signaling is associated with obesity as well as
      cardiac lipid accumulation and dysfunction, it has been difficult to separate the
      direct effects of leptin on the heart from those associated with the effects of
      leptin on body weight and fat mass. Using Cre-loxP recombinase technology, we
      developed tamoxifen-inducible, cardiomyocyte-specific leptin receptor-deficient
      mice to assess the role of leptin in regulating cardiac function. Cre recombinase
      activation in the heart resulted in transient reduction in left ventricular
      systolic function which recovered to normal levels by day 10. However, when
      cardiomyocyte leptin receptors were deleted in the setting of Cre recombinase
      induced left ventricular dysfunction, irreversible lethal heart failure was
      observed in less than 10 days in all mice. Heart failure after leptin receptor
      deletion was associated with marked decreases of cardiac mitochondrial ATP,
      phosphorylated mammalian target of rapamycin (mTOR), and AMP-activated kinase
      (pAMPK). Our results demonstrate that specific deletion of cardiomyocyte leptin
      receptors, in the presence of increased Cre recombinase expression, causes lethal
      heart failure associated with decreased cardiac energy production. These
      observations indicate that leptin plays an important role in regulating cardiac
      function in the setting of cardiac stress caused by Cre-recombinase expression,
      likely through actions on cardiomyocyte energy metabolism.

PMID- 23115125
TI  - Interleaving deep brain stimulation for a patient with both Parkinson's disease
      and essential tremor.

PMID- 23115126
TI  - Mdm2 inhibitors synergize with topoisomerase II inhibitors to induce p53
      independent pancreatic cancer cell death.
AB  - Pancreatic ductal adenocarcinoma (PDAC) represents the fourth leading cause of
      cancer death in the western world, with a 5-year survival rate below 5%. Murine
      double minute 2 (Mdm2) is an important negative regulator of the tumor suppressor
      p53. Reactivation of wild-type p53 is a promising treatment strategy, and
      inhibitors of Mdm2 have already entered clinical trials. To investigate the
      effects of Mdm2 inhibitors in PDAC, we used a murine cell line platform with a
      genetically defined status of p53. Here, we describe that Mdm2 inhibitors can act
      on a subset of murine PDAC cell lines p53 independently. Furthermore, we observed
      that Mdm2 inhibitors increase the sensitivity of murine PDAC cell lines toward
      topoisomerase II inhibitors by inducing effector caspase-independent cell death.
      The combination of Mdm2 inhibitors with topoisomerase II inhibitors acts
      independent of the survival factor NFkappaB/RelA. Mechanistically, Mdm2
      inhibitors increase topoisomerase II inhibitor-induced DNA double-strand breaks.
      We show that Mdm2 binds to Nbs1 of the Mre11-Rad50-Nijmegen breakage syndrome
      (Nbs) 1 DNA repair complex. In addition, we provide evidence that Mdm2 inhibitors
      delay DNA repair. These findings may help to design novel therapeutic strategies
      to overcome therapeutic resistance of PDAC.

PMID- 23115127
TI  - A unique case of extranodal DLBCL sharing genetic abnormalities with a
      synchronous ileal lymphoma exhibiting immunoarchitectural features of in situ
      follicular lymphoma.

PMID- 23115128
TI  - Phase composition control of calcium phosphate nanoparticles for tunable drug
      delivery kinetics and treatment of osteomyelitis. II. Antibacterial and
      osteoblastic response.
AB  - Osteomyelitis has been traditionally treated by the combination of long-term
      antibiotic therapies and surgical removal of diseased tissue. The multifunctional
      material was developed in this study with the aim to improve this therapeutic
      approach by: (a) enabling locally delivered and sustained release of antibiotics
      at a tunable rate, so as to eliminate the need for repetitive administration of
      systemically distributed antibiotics; and (b) controllably dissolving itself, so
      as to promote natural remineralization of the portion of bone lost to disease. We
      report hereby on the effect of previously synthesized calcium phosphates (CAPs)
      with tunable solubilities and drug release timescales on bacterial and
      osteoblastic cell cultures. All CAP powders exhibited satisfying antibacterial
      performance against Staphylococcus aureus, the main causative agent of
      osteomyelitis. Still, owing to its highest drug adsorption efficiency, the most
      bacteriostatically effective phase was amorphous CAP with the minimal inhibitory
      concentration of less than 1 mg/mL. At the same time, the positive cell response
      and osteogenic effect of the antibiotic-loaded CAP particles was confirmed in
      vitro for all the sparsely soluble CAP phases. Adsorption of the antibiotic onto
      CAP particles reversed the deleterious effect that the pure antibiotic exerted on
      the osteogenic activity of the osteoblastic cells. The simultaneous osteogenic
      and antimicrobial performance of the material developed in this study, altogether
      with its ability to exhibit sustained drug release, may favor its consideration
      as a material base for alternative therapeutic approaches to prolonged antibiotic
      administration and surgical debridement typically prescribed in the treatment of
      osteomyelitis.

PMID- 23115129
TI  - An accurate and efficient method to predict the electronic excitation energies of
      BODIPY fluorescent dyes.
AB  - Recently, the extreme learning machine neural network (ELMNN) as a valid
      computing method has been proposed to predict the nonlinear optical property
      successfully (Wang et al., J. Comput. Chem. 2012, 33, 231). In this work, first,
      we follow this line of work to predict the electronic excitation energies using
      the ELMNN method. Significantly, the root mean square deviation of the predicted
      electronic excitation energies of 90 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
      (BODIPY) derivatives between the predicted and experimental values has been
      reduced to 0.13 eV. Second, four groups of molecule descriptors are considered
      when building the computing models. The results show that the quantum chemical
      descriptions have the closest intrinsic relation with the electronic excitation
      energy values. Finally, a user-friendly web server (EEEBPre: Prediction of
      electronic excitation energies for BODIPY dyes), which is freely accessible to
      public at the web site: http://202.198.129.218, has been built for prediction.
      This web server can return the predicted electronic excitation energy values of
      BODIPY dyes that are high consistent with the experimental values. We hope that
      this web server would be helpful to theoretical and experimental chemists in
      related research.

PMID- 23115130
TI  - Common variation in the LRRK2 gene is a risk factor for Parkinson's disease.
AB  - BACKGROUND: Common variants in the LRRK2 gene influence the risk of Parkinson's
      disease (PD) in Asians, but whether the same is true in European-derived
      populations is less clear. METHODS: We genotyped 66 LRRK2 tagging single
      nucleotide polymorphisms (SNPs) in 575 PD patients and 689 controls from the
      northwestern United States (tier 1). PD-associated SNPs (P < .05) were then
      genotyped in an independent sample of 3617 cases and 2512 controls from the
      United States and Spain (tier 2). Logistic regression was used to model additive
      SNP genotype effects adjusted for age and sex among white individuals. RESULTS:
      Two regions showed independent association with PD in tier 1, and SNPs in both
      regions were successfully replicated in tier 2 (rs10878226, combined odds ratio
      [OR], 1.20; 95% confidence interval [CI], 1.08-1.33; P = 6.3 * 10(-4);
      rs11176013, OR, 0.89; CI, 0.83-0.95; P = 4.6 * 10(-4)). CONCLUSIONS: Our data
      suggest that common variation within LRRK2 conveys susceptibility for PD in
      individuals of European ancestry.

PMID- 23115131
TI  - Fiber-type composition in the perivertebral musculature of lizards: Implications
      for the evolution of the diapsid trunk muscles.
AB  - The perivertebral musculature of lizards is critical for the stabilization and
      the mobilization of the trunk during locomotion. Some trunk muscles are also
      involved in ventilation. This dual function of trunk muscles in locomotion and
      ventilation leads to a biomechanical conflict in many lizards and constrains
      their ability to breathe while running ("axial constraint") which likely is
      reflected by their high anaerobic scope. Furthermore, different foraging and
      predator-escape strategies were shown to correlate with the metabolic profile of
      locomotor muscles in lizards. Because knowledge of muscle's fiber-type
      composition may help to reveal a muscle's functional properties, we investigated
      the distribution pattern of muscle fiber types in the perivertebral musculature
      in two small lizard species with a generalized body shape and subjected to the
      axial constraint (Dipsosaurus dorsalis, Acanthodactylus maculatus) and one
      species that circumvents the axial constraint by means of gular pumping (Varanus
      exanthematicus). Additionally, these species differ in their predator-escape and
      foraging behaviors. Using refined enzyme-histochemical protocols, muscle fiber
      types were differentiated in serial cross-sections through the trunk, maintaining
      the anatomical relationships between the skeleton and the musculature. The fiber
      composition in Dipsosaurus and Acanthodactylus showed a highly glycolytic
      profile, consistent with their intermittent locomotor style and reliance on
      anaerobic metabolism during activity. Because early representatives of diapsids
      resemble these two species in several postcranial characters, we suggest that
      this glycolytic profile represents the plesiomorphic condition for diapsids. In
      Varanus, we found a high proportion of oxidative fibers in all muscles, which is
      in accordance with its high aerobic scope and capability of sustained locomotion.

PMID- 23115132
TI  - Calculating standard reduction potentials of [4Fe-4S] proteins.
AB  - The oxidation-reduction potentials of electron transfer proteins determine the
      driving forces for their electron transfer reactions. Although the type of redox
      site determines the intrinsic energy required to add or remove an electron, the
      electrostatic interaction energy between the redox site and its surrounding
      environment can greatly shift the redox potentials. Here, a method for
      calculating the reduction potential versus the standard hydrogen electrode, E
      degrees , of a metalloprotein using a combination of density functional theory
      and continuum electrostatics is presented. This work focuses on the methodology
      for the continuum electrostatics calculations, including various factors that may
      affect the accuracy. The calculations are demonstrated using crystal structures
      of six homologous HiPIPs, which give E degrees  that are in excellent agreement
      with experimental results.

PMID- 23115133
TI  - Protective stepping response in Parkinsonian patients and the effect of
      vibrotactile feedback.
AB  - The objectives of this study were (1) to characterize protective stepping
      responses to unpredictable forward/backward postural perturbation in Parkinson's
      disease (PD) and (2) to assess whether vibrotactile cues of the impending fall
      improve the stepping response. Twenty mild PD patients, 7 advanced PD patients,
      and 17 age-matched controls stood on a platform moving unpredictably forward and
      backward, requiring a protective step to maintain balance. Direction-coded
      vibrotactile cues, triggered by leg tilt, were provided to prompt step
      generation. All subjects showed quicker reaction time, shorter steps, and smaller
      total trunk displacement when stepping backward than when stepping forward.
      Advanced PD patients took shorter, slower, and an increased number of protective
      steps. The only abnormality observed in mild PD patients was slightly slower
      backward steps. Vibrotactile feedback reduced the amount of trunk displacement
      observed before taking a protective step but did not improve any abnormality in
      PD patients. Early PD patients had near-normal protective stepping responses to
      unpredictable perturbations, but advanced patients made slow and short steps both
      forward and backward. Given that latencies were preserved even in unpredictable
      conditions, step slowness and hypometria are the primary abnormalities of the
      stepping response in PD. As voluntary locomotor stepping in PD is reported to
      improve with sensory feedback, the lack of such improvement in our study implies
      that additional sensory cues cannot help automatic reflex-like stepping reactions
      in PD patients.

PMID- 23115134
TI  - Microsatellite primers for the neotropical epiphyte Epidendrum firmum
      (Orchidaceae).
AB  - PREMISE OF THE STUDY: Ten microsatellite loci were isolated and characterized for
      the neotropical epiphytic orchid Epidendrum firmum to examine levels of genetic
      diversity and genetic structure at multiple spatial scales. METHODS AND RESULTS:
      We screened loci in 12-25 individuals from each of two populations in Costa Rica
      and identified 10 polymorphic loci. The number of alleles per locus ranged from
      one to 15 while observed heterozygosity for polymorphic loci ranged from 0.360 to
      0.960. CONCLUSIONS: Primers for these informative genetic markers will be useful
      for quantifying genetic diversity, spatial genetic structure, and gene flow in E.
      firmum.

PMID- 23115135
TI  - Isolation of microsatellite primers for Melampyrum sylvaticum (Orobanchaceae), an
      endangered plant in the United Kingdom.
AB  - PREMISE OF THE STUDY: Microsatellite markers were developed for the hemiparasitic
      plant Melampyrum sylvaticum to investigate the breeding system, genetic
      diversity, and structure of populations in the United Kingdom, Sweden, and
      Norway. METHODS AND RESULTS: Microsatellites were isolated from genomic DNA using
      an enrichment protocol. Twenty-nine loci were characterized in two individuals
      from each of 15 geographically disparate populations ("global"). Seven
      polymorphic loci were further characterized in one population ("local"). The
      number of alleles per locus ranged from two to 12 in the global sample and one to
      seven in the local sample. The expected heterozygosity ranged from 0-0.75, the
      observed heterozygosity from 0-0.1, and the inbreeding coefficient from 0.84-1 in
      the local sample. CONCLUSIONS: The results show the utility of these novel
      polymorphic microsatellite markers for further conservation genetic analyses. The
      strong deficit of heterozygosity across all loci in the local sample suggests the
      species may be inbreeding.

PMID- 23115136
TI  - Mechanism of higher plant gravity sensing.
AB  - Higher plants have developed statocytes, specialized tissues or cells for gravity
      sensing, and subsequent signal formation. Root and shoot statocytes commonly
      harbor a number of amyloplasts, and amyloplast sedimentation in the direction of
      gravity is a critical process in gravity sensing. However, the molecular
      mechanism underlying amyloplast-dependent gravity sensing is largely unknown. In
      this review, we mainly describe the molecular basis for the gravity sensing
      mechanism, i.e., the molecules and their functions involved in amyloplast
      sedimentation. Several analyses of statocyte images in living plant organs have
      implied differences in the regulation of amyloplast movements between root and
      shoot statocytes. Amyloplasts in shoot statocytes display not only sedimentable
      but upward, saltatory movements, but the latter are rarely observed in root
      statocytes. A series of genetic studies on shoot gravitropism mutants of
      Arabidopsis thaliana has revealed that two intracellular components, the vacuolar
      membrane (VM) and actin microfilaments (AFs), within the shoot statocyte play
      important roles in amyloplast dynamics. Flexible VM structures surrounding the
      amyloplasts seem to allow them to freely sediment toward the bottom of cells. In
      contrast, long actin cables mediate the saltatory movements of amyloplasts. Thus,
      amyloplasts in shoot statocytes undergo a dynamic equilibrium of movement, and a
      proper intracellular environment for statocytes is essential for normal shoot
      gravitropism. Further analyses to identify the molecular regulators of amyloplast
      dynamics, including sedimentation, may contribute to an understanding of the
      gravity sensing mechanism in higher plants.

PMID- 23115137
TI  - Development of microsatellite markers from Mussaenda pubescens (Rubiaceae).
AB  - PREMISE OF THE STUDY: Microsatellite markers were developed and characterized in
      Mussaenda pubescens for further study of its levels of genetic diversity and
      changes in population genetic structure in reproductive character displacement
      and in shifts of sexual systems. METHODS AND RESULTS: Nineteen microsatellite
      loci were amplified successfully in M. pubescens, 17 of which were polymorphic. A
      maximum of eight alleles were detected per locus in 68 individuals at population
      level. The observed and expected heterozygosities varied from 0 to 1.000 and 0 to
      0.882, respectively. CONCLUSIONS: These newly developed microsatellite markers
      will be useful in further investigations of genetic diversity and gene flow among
      populations of M. pubescens and its congeneric species.

PMID- 23115138
TI  - CKD.QLD: chronic kidney disease surveillance and research in Queensland,
      Australia.
AB  - BACKGROUND: Chronic kidney disease (CKD) is recognized as a major public health
      problem in Australia with significant mortality, morbidity and economic burden.
      However, there is no comprehensive surveillance programme to collect, collate and
      analyse data on CKD in a systematic way. METHODS: We describe an initiative
      called CKD Queensland (CKD.QLD), which was established in 2009 to address this
      deficiency, and outline the processes and progress made to date. The foundation
      is a CKD Registry of all CKD patients attending public health renal services in
      Queensland, and patient recruitment and data capture have started. RESULTS: We
      have established through early work of CKD.QLD that there are over 11,500 CKD
      patients attending public renal services in Queensland, and these are the target
      population for our registry. Progress so far includes conducting two CKD clinic
      site surveys, consenting over 3000 patients into the registry and initiation of
      baseline data analysis of the first 600 patients enrolled at the Royal Brisbane
      and Women's Hospital (RBWH) site. In addition, research studies in dietary intake
      and CKD outcomes and in models of care in CKD patient management are underway.
      CONCLUSIONS: Through the CKD Registry, we will define the distribution of CKD
      patients referred to renal practices in the public system in Queensland by
      region, remoteness, age, gender, ethnicity and socioeconomic status. We will
      define the clinical characteristics of those patients, and the CKD associations,
      stages, co-morbidities and current management. We will follow the course and
      outcomes in individuals over time, as well as group trends over time. Through our
      activities and outcomes, we are aiming to provide a nidus for other states in
      Australia to join in a national CKD registry and network.

PMID- 23115139
TI  - Chronic renal disease in children aged 5-18 years: a population-based survey in
      Turkey, the CREDIT-C study.
AB  - BACKGROUND: Data on the epidemiology of chronic kidney disease (CKD), which is a
      serious health problem and refers to a condition related to irreversible kidney
      damage that further progress to end-stage renal disease in children, are
      insufficient and data that are available were based on hospital records. The aim
      of this nationwide, population-based field study was to determine the prevalence
      of CKD in children in Turkey and to evaluate the association between CKD and
      possible risk factors such as obesity and hypertension. METHODS: The study was
      the paediatric stratum (3622 children aged 5-18 years) of the previously
      published population-based survey of Chronic REnal Disease In Turkey (CREDIT
      study). Medical data were collected through home visits and interviews between
      November 2007 and July 2008; height, weight and blood pressure were also
      measured. Serum creatinine, total cholesterol, uric acid and complete blood count
      were determined from 12-h fasting blood samples, and spot urine tests were
      performed for subjects who gave consent to laboratory evaluation. RESULTS:
      Following adjustment according to gender, residence, age groups and geographical
      regions, the prevalence of children with estimated glomerular filtration rate
      (eGFR) <75 mL/min/1.73 m(2) was 0.94 [95% confidence interval (CI): 0.63-1.35],
      and the prevalence of children with CKD Stages 3-5 [National Kidney Foundation
      Kidney Disease Outcomes Quality Initiative (K/DOQI)] was 2600 (95% CI 1100-5100)
      per million age related population. The mean eGFR was found to increase with age;
      the ratios of children with eGFR <90 and <75 mL/min/1.73 m(2) were higher in
      younger age groups. The frequencies of overweight and obese children were 9.3 and
      8.9%, respectively, and the mean eGFR was lower in patients with higher body mass
      index. The prevalence of hypertension and hypercholesterolaemia was 6.1 and 5.8%,
      respectively; the mean eGFR was lower in children with hypercholesterolaemia.
      CONCLUSIONS: This is the first population-based CKD study performed in children
      aged 5-18 years. The prevalence of CKD in our study was 25-100 times greater than
      that found in previous hospital-based studies. Our data suggest that approaches
      focusing on patients in tertiary centres are likely to lead to patients being
      missed at early stages of CKD and that a vast majority of these children will
      never develop symptomatic CKD during childhood.

PMID- 23115140
TI  - The impact of CKD identification in large countries: the burden of illness.
AB  - Chronic kidney disease (CKD) is becoming a major public health issue worldwide
      and an important contributor to the overall non-communicable disease burden. It
      is associated with major serious consequences including increased risk of
      mortality, end-stage renal disease, accelerated cardiovascular disease (CVD),
      mineral and bone disease, adverse metabolic and nutritional consequences,
      infections, reduced cognitive function and increased risk of acute kidney injury.
      Mortality from CVD is estimated to be at least 8- to 10-fold higher in CKD
      subjects compared to non-CKD subjects. Estimates from different parts of the
      world, especially large countries, reveal an increasing incidence and prevalence
      of CKD. This is partly attributed to the global increasing prevalence of
      diabetes, hypertension, obesity and CVD. The global economic impact of CKD is
      tremendous. This calls for the need of a global effort to raise awareness of CKD,
      to incorporate prevention of CKD progression program in the public health agenda
      and to implement programs for early screening and detection of CKD, especially in
      high-risk population so to allow early institution of treatment to prevent
      further CKD progression. Hopefully, by doing so, we may reduce CKD burden
      globally over time and, most importantly, improve the health outcomes of patients
      with CKD.

PMID- 23115141
TI  - Engaging primary care in CKD initiatives: the UK experience.
AB  - Over the last decade, since the introduction of an international classification
      of chronic kidney disease (CKD) and the development of simple tools to detect
      people with CKD, primary care has had to adapt to a new paradigm of disease.
      Significantly, improved identification of CKD, and increased awareness and
      understanding of the potential associated adverse outcomes, has in turn required
      the development, implementation and integration of new policies, models and
      pathways of care. The UK health care system, including primary care, is uniquely
      positioned to respond to new initiatives. Despite early reservations, CKD has
      gone from an unheard of condition in primary care prior to 2006 to one where
      people with this condition are recorded in disease registers and increasingly
      managed in accordance with evidence-based guidance. National and local
      initiatives implemented together have contributed to the improved understanding
      and management of CKD in primary care in the UK and are showing signs of having
      made significant health gains in CKD.

PMID- 23115142
TI  - From preeclampsia to renal disease: a role of angiogenic factors and the renin
      angiotensin aldosterone system?
AB  - Complicating up to 8% of pregnancies, preeclampsia is the most common glomerular
      disease worldwide and remains a leading cause of infant and maternal morbidity
      and mortality. Although the exact pathogenesis of this syndrome of hypertension
      and proteinuria is still incomplete, a consistent line of evidence has identified
      an imbalance of proangiogenic and anti-angiogenic proteins as a key factor in the
      development of preeclampsia. Furthermore, more attention has been recently
      addressed to the renin-angiotensin aldosterone system (RAAS), to provide
      understanding on the hypertension of preeclampsia. The imbalance of the RAAS and
      the imbalance between angiogenic and anti-angiogenic factors, which may be both
      common to preeclampsia and chronic kidney disease (CKD), might explain why a
      history of preeclampsia predisposes women to develop CKD. In this review, we
      briefly describe the characteristics of preeclampsia with a focus on the
      mechanisms of angiogenesis and the RAAS and its role in the pathogenesis of
      preeclampsia. Our main focus will be on the intriguing association between
      preeclampsia and the subsequent increased risk of developing CKD and on the
      potential mechanisms by which the risk of CKD is elevated in women with a history
      of preeclampsia.

PMID- 23115143
TI  - Medical clearance: an issue of professional autonomy, not a crutch.

PMID- 23115144
TI  - Periodontitis and the heart.

PMID- 23115145
TI  - Caries classification.

PMID- 23115147
TI  - Dental procedures and risk of experiencing a second vascular event in a Medicare
      population.
AB  - BACKGROUND: Practice guidelines historically have recommended postponing dental
      care after ischemic vascular events. The authors examined an administrative data
      set to determine whether dental procedures increased patients' risk of
      experiencing a second vascular event. METHODS: The authors examined a data set of
      50,329 participants in the Medicare Current Beneficiary Survey to identify those
      who had had a vascular event (n = 2,035) and a second event (n = 445) while in
      the survey. They used Cox proportional hazards regression to study associations
      between dental procedures performed within 30, 60, 90 or 180 days after a first
      event and the risk of experiencing a second vascular event. RESULTS: Dental
      procedures of any kind, and invasive procedures considered separately, were not
      associated with patients' risk of experiencing second vascular events across all
      periods examined. Most hazard ratios associated with dental procedures were less
      than 1.0, although none differed significantly from 1.0. CONCLUSIONS: The authors
      found that community-dwelling Medicare beneficiaries who underwent dental
      procedures within 30 to 180 days after an ischemic vascular event, including
      those that produce a bacteremia consistently, were not at an increased risk of
      experiencing a second event. CLINICAL IMPLICATIONS: The results of this study
      suggest that clinicians should reassess historical recommendations that dental
      care in this population be postponed for as long as six months after an ischemic
      vascular event.

PMID- 23115148
TI  - Evaluation of the spatter-reduction effectiveness of two dry-field isolation
      techniques.
AB  - BACKGROUND: The authors conducted a study to compare the effectiveness of two dry
      field isolation techniques with that of a control technique (no isolation) in
      reducing spatter from a dental operative site. METHODS: The authors designed a
      benchtop experiment to evaluate spatter patterns after performing simulated
      occlusal surface preparations on three typodont teeth in a dental manikin.
      Fluorescein dye served as the marker to enable visualization of the spatter
      distribution. The authors compared the effectiveness of a nonisolated control
      consisting of high-volume evacuation (HVE) alone with that of two dry-field
      isolation techniques: a dental dam with HVE and the Isolite system (Isolite
      Systems, Santa Barbara, Calif). RESULTS: The authors performed a two-way analysis
      of variance. Both the Isolite device and the dental dam with HVE exhibited a
      significant decrease in the number of contaminated squares (P < .001) compared
      with that for the nonisolated control. In addition, overall, the results showed
      no statistically significant difference between the Isolite system and the dental
      dam with HVE (P = .126). CONCLUSIONS: The study results showed that use of a
      dental dam with HVE or the Isolite system significantly reduced spatter overall
      compared with use of HVE alone. CLINICAL IMPLICATIONS: Isolation with a dental
      dam and HVE or with the Isolite system appears to aid in the reduction of spatter
      during operative dental procedures, potentially reducing exposure to oral
      pathogens.

PMID- 23115149
TI  - Asymptomatic bilateral facial swelling.

PMID- 23115150
TI  - Craniofacial morphologic predictors of oral appliance outcomes in patients with
      obstructive sleep apnea.
AB  - BACKGROUND: Oral appliances (OAs) that advance the mandible can improve the
      intake of oxygen and reduce the number of apneic episodes in patients who have
      obstructive sleep apnea. Although OAs are not as effective as continuous positive
      airway pressure therapy, they are an important therapeutic consideration for
      patients with obstructive sleep apnea. However, the ability to predict efficacy
      of OAs is limited. The authors conducted a study to assess the value of relevant
      clinical and cephalometric variables that can help predict the outcome of OA use
      in an Asian population. METHODS: Fifty-two Taiwanese patients consecutively
      treated with OAs were included in the study. Relevant clinical and cephalometric
      variables were determined at baseline. Treatment success was defined as a
      reduction of more than 50 percent in the apnea-hypopnea index and the residual
      apnea-hypopnea index less than 10 per hour with OAs. The predictive value of
      variables for treatment outcome was evaluated by means of univariate and
      multivariate analyses. A receiver operating characteristic curve for the
      multivariate logistic regression model was constructed. RESULTS: A good outcome
      was found in 29 participants (56 percent). Minimal retroglossal airway,
      mandibular position and anterior face height were significant predictors of OA
      treatment success. The area under the receiver operating characteristic curve was
      0.862, reflecting good model discrimination. CONCLUSIONS: Some cephalometric
      variables had a predictive value for the outcome of OA use. OA treatment outcome
      was favorable in patients with certain craniofacial structures such as narrow
      minimal retroglossal airway, mandibular retrusion and short anterior face height.
      CLINICAL IMPLICATIONS: Practitioners should consider OAs for treatment of
      patients with obstructive sleep apnea who have narrow minimal retroglossal
      airways, mandibular retrusion and short anterior face heights.

PMID- 23115151
TI  - Crown retention with three resin-modified glass ionomer luting agents.
AB  - BACKGROUND: The author used a standardized technique to investigate the retentive
      properties of three resin-modified glass ionomer (RMGI) cements in the
      cementation of precious gold copings. METHODS: The author machined premolars on a
      jeweler's lathe to a taper of 16 +/- 0.5 degrees. The occlusal table measured 4
      millimeters. The author fabricated wax patterns with a uniform 360-degree
      internal fitting surface of 2.7 mm. Each group consisted of 10 samples. The
      author invested the wax patterns and cast them in gold. He cemented the copings
      as follows: group 1, RelyX Luting Plus (3M ESPE, St. Paul, Minn.); group 2, Fuji
      Plus Resin-Reinforced, Multipurpose Cement (GC America, Alsip, Ill.) and group 3,
      UltraCem Resin-Reinforced Glass Ionomer Cement (Ultradent Products, South Jordan,
      Utah). The author performed the cementation under controlled pressure. After 24
      hours, he applied a tensile force until catastrophic failure (expressed as
      kilogram force at failure) occurred. The author used analysis of variance for
      statistical analysis (P < .05). RESULTS: A statistically significant difference
      was demonstrated between UltraCem and the other two cements tested (P < .05),
      whereas no statistical difference could be demonstrated between RelyX and Fuji
      Plus (P > .05). CONCLUSIONS: By using an established standardized ex vivo crown
      retention test, the author found that the three RMGI cements he tested generated
      retention values that were clinically desirable when compared with those of other
      commercially available cements that have been used successfully for many years.
      UltraCem scored the highest values, followed by Fuji Plus and RelyX,
      respectively. CLINICAL IMPLICATIONS: Cementation of precious alloy crowns and
      bridges by using RMGI cements tested in this study generated retentive values
      that mostly exceeded those of conventional luting agents.

PMID- 23115153
TI  - Cariously exposed pulps may benefit from vital pulp therapies.

PMID- 23115152
TI  - Sleep bruxism and myofascial temporomandibular disorders: a laboratory-based
      polysomnographic investigation.
AB  - BACKGROUND: Many dentists believe that sleep bruxism (SB) is a pathogenic factor
      in myofascial temporomandibular disorder (TMD), but almost all supportive data
      rely on patients' self-reports rather than on direct observation. METHODS: The
      authors administered a structured self-report interview to determine whether a
      large and well-characterized sample of patients with myofascial TMD (124 women)
      experienced SB more often than did matched control participants (46 women). The
      authors then used data from a two-night laboratory-based polysomnographic (PSG)
      study to determine whether the case participants exhibited more SB than the
      control participants. RESULTS: The results of independent sample t tests and
      chi(2) analyses showed that, although self-reported rates of SB were
      significantly higher in case participants (55.3 percent) than in control
      participants (15.2 percent), PSG-based measures showed much lower and
      statistically similar rates of SB in the two groups (9.7 percent and 10.9
      percent, respectively). Grinding noises were common in both case participants
      (59.7 percent) and control participants (78.3 percent). CONCLUSIONS: Most case
      participants did not exhibit SB, and the common belief that SB is a sufficient
      explanation for myofascial TMD should be abandoned. CLINICAL IMPLICATIONS:
      Although other reasons to consider treating SB may exist, misplaced concern about
      SB's sustaining or exacerbating a chronic myofascial TMD condition should not be
      used to justify SB treatment.

PMID- 23115155
TI  - The importance of key performance indicators.

PMID- 23115154
TI  - Examining the accuracy of caregivers' assessments of young children's oral health
      status.
AB  - BACKGROUND: Caregivers' perceptions of their young children's oral health status
      (OHS) are a strong determinant of whether the children visit a dentist. Our aims
      were to quantify the correlation between caregivers' assessments and their
      children's clinically determined restorative treatment needs, while investigating
      factors related to this association. METHODS: One hundred eight caregivers
      assessed their children's OHS by answering a question on the self-reported
      National Health and Nutrition Examination Survey III instrument. Children
      underwent clinical oral examinations at one of two study sites of the Carolina
      Oral Health Literacy Project: a dental school-based clinic and a community-based
      health clinic. Examiners recorded the children's clinical treatment needs by
      using a modification of the caries severity index. The authors quantified
      concordance between the two measures with use of the Spearman rank correlation
      (rho) and Kendall tau rank correlation, whereas they assessed differences in
      sociodemographic factors and oral health literacy (OHL) levels by using a
      homogeneity chi(2) test (P < .2 criterion). RESULTS: The concordance between
      caregivers' assessments and clinically determined OHS was lower for younger
      children (< 2 years, rho = 0.29 versus = 2 years, rho = 0.63 [homogeneity P =
      .03]), a pattern that was evident in the community clinic but not in the
      university clinic. Caregivers' age, education and OHL did not influence the
      accuracy of self-reports. CONCLUSIONS: For children younger than 2 years,
      caregivers' assessments correlated poorly with clinical needs, which routinely
      were underestimated.  Practice Implications. These findings underscore the
      importance of preventive dental visits at a young age and the early establishment
      of a dental home.

PMID- 23115156
TI  - If I learn the identity of a patient's new dentist, should I inform the dentist
      of the patient's health history, given that the patient has indicated he will not
      share this information in full?

PMID- 23115157
TI  - Marginal discoloration of all-ceramic restorations cemented adhesively versus
      nonadhesively.
AB  - BACKGROUND: The authors conducted a systematic review to correlate the clinical
      incidence of marginal discoloration of all-ceramic restorations with the mode of
      cementation (adhesive versus nonadhesive). TYPES OF STUDIES REVIEWED: The authors
      conducted a literature search by using electronic databases, relevant references,
      database citations and journal hand searches for clinical studies of marginal
      discoloration of all-ceramic restorations with a mean follow-up time of at least
      five years. The search period spanned January 1990 through February 2011. The
      authors reported and compared summary estimates and five-year event rates.
      RESULTS: The authors selected 16 studies for final analysis from an initial yield
      of 346 articles. The mean observation time ranged between five and 10 years. The
      majority of studies used adhesive luting procedures for definitive cementation.
      In only one study did investigators report regarding the incidence of marginal
      discoloration of both adhesively and nonadhesively cemented all-ceramic
      restorations, and the difference between the luting types in terms of
      discoloration was not statistically significant (P = .5). CLINICAL IMPLICATIONS:
      The results of this systematic review showed that there is a lack of studies with
      findings regarding marginal discoloration rates of nonadhesively luted all
      ceramic restorations. Unacceptable marginal discoloration rates of adhesively
      luted all-ceramic prostheses were relatively low even at 10 years of service.

PMID- 23115158
TI  - Overexpression of isocitrate dehydrogenase mutant proteins renders glioma cells
      more sensitive to radiation.
AB  - Mutations in isocitrate dehydrogenase 1 (IDH1) or 2 (IDH2) are found in a subset
      of gliomas. Among the many phenotypic differences between mutant and wild-type
      IDH1/2 gliomas, the most salient is that IDH1/2 mutant glioma patients
      demonstrate markedly improved survival compared with IDH1/2 wild-type glioma
      patients. To address the mechanism underlying the superior clinical outcome of
      IDH1/2 mutant glioma patients, we investigated whether overexpression of the
      IDH1(R132H) protein could affect response to therapy in the context of an
      isogenic glioma cell background. Stable clonal U87MG and U373MG cell lines
      overexpressing IDH1(WT) and IDH1(R132H) were generated, as well as U87MG cell
      lines overexpressing IDH2(WT) and IDH2(R172K). In vitro experiments were
      conducted to characterize baseline growth and migration and response to radiation
      and temozolomide. In addition, reactive oxygen species (ROS) levels were measured
      under various conditions. U87MG-IDH1(R132H) cells, U373MG-IDH1(R132H) cells, and
      U87MG-IDH2(R172K) cells demonstrated increased sensitivity to radiation but not
      to temozolomide. Radiosensitization of U87MG-IDH1(R132H) cells was accompanied by
      increased apoptosis and accentuated ROS generation, and this effect was abrogated
      by the presence of the ROS scavenger N-acetyl-cysteine. Interestingly, U87MG
      IDH1(R132H) cells also displayed decreased growth at higher cell density and in
      soft agar, as well as decreased migration. Overexpression of IDH1(R132H) and
      IDH2(R172K) mutant protein in glioblastoma cells resulted in increased radiation
      sensitivity and altered ROS metabolism and suppression of growth and migration in
      vitro. These findings provide insight into possible mechanisms contributing to
      the improved outcomes observed in patients with IDH1/2 mutant gliomas.

PMID- 23115159
TI  - High levels of phosphorylated MAP kinase are associated with poor survival among
      patients with glioblastoma during the temozolomide era.
AB  - We investigated whether high levels of activated mitogen-activated protein kinase
      (p-MAPK) were associated with poor survival among patients with newly diagnosed
      glioblastoma during the temozolomide era. Nuclear p-MAPK expression of 108
      patients with GBM was quantified and categorized in the following levels: low (0%
      10%), medium (11%-40%), and high (41%-100%). Independent predictors of overall
      survival were determined using a multivariate Cox proportional hazards model. Our
      study included 108 patients with newly diagnosed GBM. Median age was 65 years,
      and 74% had high Karnofsky performance status (KPS >= 80). Median overall
      survival among all patients was 19.5 months. Activated MAPK expression levels of
      <10%, 11%-40%, and >= 41% were observed in 33 (30.6%), 37 (34.3%), and 38 (35.2%)
      patients, respectively. Median survival for low, medium, and high p-MAPK
      expression was 32.4, 18.2, and 12.5 months, respectively. Multivariate analysis
      showed 2.4-times hazard of death among patients with intermediate p-MAPK than low
      p-MAPK expression (hazard ratio [HR], 2.4; P = .02); high-expression patients
      were 3.9 times more likely to die, compared with patients with low p-MAPK (HR,
      3.9; P = .007). Patients aged >= 65 years (HR, 2.8; P = .002) with KPS < 80 (HR,
      3.1; P = .0003) and biopsy or partial resection (HR, 1.9; P = .02) had higher
      hazard of death. MGMT and PTEN expression were not associated with survival
      differences. This study provides quantitative means of evaluating p-MAPK in
      patients with GBM. It confirms the significant and independent prognostic
      relevance of p-MAPK in predicting survival of patients with GBM treated in the
      temozolomide era and highlights the need for therapies targeting the p-MAPK
      oncogenic pathway.

PMID- 23115161
TI  - Whole-genome sequence of Cupriavidus sp. strain BIS7, a heavy-metal-resistant
      bacterium.
AB  - Cupriavidus sp. strain BIS7 is a Malaysian tropical soil bacterium that exhibits
      broad heavy-metal resistance [Co(II), Zn(II), Ni(II), Se(IV), Cu(II), chromate,
      Co(III), Fe(II), and Fe(III)]. It is particularly resistant to Fe(II), Fe(III),
      and Zn(II). Here we present the assembly and annotation of its genome.

PMID- 23115160
TI  - Detection of glioblastoma response to temozolomide combined with bevacizumab
      based on MUMRI and MUPET imaging reveals [18F]-fluoro-L-thymidine as an early and
      robust predictive marker for treatment efficacy.
AB  - The individualized care of glioma patients ought to benefit from imaging
      biomarkers as precocious predictors of therapeutic efficacy. Contrast enhanced
      MRI and [(18)F]-fluorodeoxyglucose (FDG)-PET are routinely used in clinical
      settings; their ability to forecast the therapeutic response is controversial.
      The objectives of our preclinical study were to analyze sensitive uMRI and/or
      uPET imaging biomarkers to predict the efficacy of anti-angiogenic and/or
      chemotherapeutic regimens. Human U87 and U251 orthotopic glioma models were
      implanted in nude rats. Temozolomide and/or bevacizumab were administered. uMRI
      (anatomical, diffusion, and microrheological parameters) and uPET ([(18)F]-FDG
      and [(18)F]-fluoro-l-thymidine [FLT]-PET) studies were undertaken soon (t(1))
      after treatment initiation compared with late anatomical uMRI evaluation of tumor
      volume (t(2)) and overall survival. In both models, FDG and FLT uptakes were
      attenuated at t(1) in response to temozolomide alone or with bevacizumab. The
      distribution of FLT, reflecting intratumoral heterogeneity, was also modified.
      FDG was less predictive for treatment efficacy than was FLT (also highly
      correlated with outcome, P < .001 for both models). Cerebral blood volume was
      significantly decreased by temozolomide + bevacizumab and was correlated with
      survival for rats with U87 implants. While FLT was highly predictive of treatment
      efficacy, a combination of imaging biomarkers was superior to any one alone (P <
      .0001 in both tumors with outcome). Our results indicate that FLT is a sensitive
      predictor of treatment efficacy and that predictability is enhanced by a
      combination of imaging biomarkers. These findings may translate clinically in
      that individualized glioma treatments could be decided in given patients after
      PET/MRI examinations.

PMID- 23115162
TI  - A longitudinal study of the long-term consequences of drinking during pregnancy:
      heavy in utero alcohol exposure disrupts the normal processes of brain
      development.
AB  - Exposure to alcohol in utero can cause birth defects, including face and brain
      abnormalities, and is the most common preventable cause of intellectual
      disabilities. Here we use structural magnetic resonance imaging to measure
      cortical volume change longitudinally in a cohort of human children and youth
      with prenatal alcohol exposure (PAE) and a group of unexposed control subjects,
      demonstrating that the normal processes of brain maturation are disrupted in
      individuals whose mothers drank heavily during pregnancy. Trajectories of
      cortical volume change within children and youth with PAE differed from those of
      unexposed control subjects in posterior brain regions, particularly in the
      parietal cortex. In these areas, control children appear to show a particularly
      plastic cortex with a prolonged pattern of cortical volume increases followed by
      equally vigorous volume loss during adolescence, while the alcohol-exposed
      participants showed primarily volume loss, demonstrating decreased plasticity.
      Furthermore, smaller volume changes between scans were associated with lower
      intelligence and worse facial morphology in both groups, and were related to the
      amount of PAE during each trimester of pregnancy in the exposed group. This
      demonstrates that measures of IQ and facial dysmorphology predict, to some
      degree, the structural brain development that occurs in subsequent years. These
      results are encouraging in that interventions aimed at altering "experience" over
      time may improve brain trajectories in individuals with heavy PAE and possibly
      other neurodevelopmental disorders.

PMID- 23115163
TI  - Cortical sensory plasticity in a model of migraine with aura.
AB  - The migraine attack is characterized by alterations in sensory perception, such
      as photophobia or allodynia, which have in common an uncomfortable amplification
      of the percept. It is not known how these changes arise. We evaluated the ability
      of cortical spreading depression (CSD), the proposed mechanism of the migraine
      aura, to shape the cortical activity that underlies sensory perception. We
      measured forepaw- and hindpaw-evoked sensory responses in rat, before and after
      CSD, using multielectrode array recordings and two-dimensional optical
      spectroscopy. CSD significantly altered cortical sensory processing on a
      timescale compatible with the duration of the migraine attack. Both
      electrophysiological and hemodynamic maps had a reduced surface area (were
      sharpened) after CSD. Electrophysiological responses were potentiated at the
      receptive field center but suppressed in surround regions. Finally, the normal
      adaptation of sensory-evoked responses was attenuated at the receptive field
      center. In summary, we show that CSD induces changes in the evoked cortical
      response that are consistent with known mechanisms of cortical plasticity. These
      mechanisms provide a novel neurobiological substrate to explain the sensory
      alterations of the migraine attack.

PMID- 23115164
TI  - Axonal conduction block as a novel mechanism of prepulse inhibition.
AB  - In prepulse inhibition (PPI), the startle response to a strong, unexpected
      stimulus is diminished if shortly preceded by the onset of a different stimulus.
      Because deficits in this inhibitory gating process are a hallmark feature of
      schizophrenia and certain other psychiatric disorders, the mechanisms underlying
      PPI are of significant interest. We previously used the invertebrate model system
      Tritonia diomedea to identify the first cellular mechanism for PPI--presynaptic
      inhibition of transmitter release from the afferent neurons (S-cells) mediating
      the startle response. Here, we report the involvement of a second, more powerful
      PPI mechanism in Tritonia: prepulse-elicited conduction block of action
      potentials traveling in the startle pathway caused by identified inhibitory
      interneurons activated by the prepulse. This example of axo-axonic conduction
      block--neurons in one pathway inhibiting the propagation of action potentials in
      another--represents a novel and potent mechanism of sensory gating in prepulse
      inhibition.

PMID- 23115165
TI  - Reduction of synaptojanin 1 ameliorates synaptic and behavioral impairments in a
      mouse model of Alzheimer's disease.
AB  - Decades of research have correlated increased levels of amyloid-beta peptide
      (Abeta) with neuropathological progression in Alzheimer's disease (AD) patients
      and transgenic models. Abeta precipitates synaptic and neuronal anomalies by
      perturbing intracellular signaling, which, in turn, may underlie cognitive
      impairment. Abeta also alters lipid metabolism, notably causing a deficiency of
      phosphatidylinositol 4,5-bisphosphate [PI(4,5)P(2)], a phospholipid that
      regulates critical neuronal functions. Haploinsufficiency of the gene encoding
      synaptojanin 1 (Synj1), a major PI(4,5)P(2) phosphatase in the brain, provided
      protection against PI(4,5)P(2) breakdown and electrophysiological deficits
      attributable to Abeta. Based on these data, we tested whether reduction of Synj1
      could rescue cognitive deficits and Abeta-induced morphological alterations of
      synapses. We found that hemizygous deletion of Synj1 in the context of a mouse
      model expressing the Swedish mutant of amyloid precursor protein rescues deficits
      in learning and memory without affecting amyloid load. Synj1 heterozygosity also
      rescued PI(4,5)P(2) deficiency in a synaptosome-enriched fraction from the brain
      of Tg2576 mice. Genetic disruption of Synj1 attenuated Abeta oligomer-induced
      changes in dendritic spines of cultured hippocampal neurons, sparing mature spine
      classes, which corroborates the protective role for Synj1 reduction against Abeta
      insult at the synapse. These results indicate that Synj1 reduction ameliorates AD
      associated behavioral and synaptic deficits, providing evidence that Synj1 and,
      more generally, phosphoinositide metabolism may be promising therapeutic targets.
      Our work expands on recent studies identifying lipid metabolism and lipid
      modifying enzymes as targets of AD-associated synaptic and behavioral impairment.

PMID- 23115166
TI  - Not lost in translation: neural responses shared across languages.
AB  - How similar are the brains of listeners who hear the same content expressed in
      different languages? We directly compared the fMRI response time courses of
      English speakers and Russian speakers who listened to a real-life Russian
      narrative and its English translation. In the translation, we tried to preserve
      the content of the narrative while reducing the structural similarities across
      languages. The story evoked similar brain responses, invariant to the structural
      changes across languages, beginning just outside early auditory areas and
      extending through temporal, parietal, and frontal cerebral cortices. The
      similarity of responses across languages was nearly equal to the similarity of
      responses within each language group. The present results demonstrate that the
      human brain processes real-life information in a manner that is largely
      insensitive to the language in which that information is conveyed. The methods
      introduced here can potentially be used to quantify the transmission of meaning
      across cultural and linguistic boundaries.

PMID- 23115167
TI  - Separable mechanisms underlying global feature-based attention.
AB  - Feature-based attention is known to operate in a spatially global manner, in that
      the selection of attended features is not bound to the spatial focus of
      attention. Here we used electromagnetic recordings in human observers to
      characterize the spatiotemporal signature of such global selection of an
      orientation feature. Observers performed a simple orientation-discrimination task
      while ignoring task-irrelevant orientation probes outside the focus of attention.
      We observed that global feature-based selection, indexed by the brain response to
      unattended orientation probes, is composed of separable functional components.
      One such component reflects global selection based on the similarity of the probe
      with task-relevant orientation values ("template matching"), which is followed by
      a component reflecting selection based on the similarity of the probe with the
      orientation value under discrimination in the focus of attention ("discrimination
      matching"). Importantly, template matching occurs at ~150 ms after stimulus
      onset, ~80 ms before the onset of discrimination matching. Moreover, source
      activity underlying template matching and discrimination matching was found to
      originate from ventral extrastriate cortex, with the former being generated in
      more anterolateral and the latter in more posteromedial parts, suggesting
      template matching to occur in visual cortex higher up in the visual processing
      hierarchy than discrimination matching. We take these observations to indicate
      that the population-level signature of global feature-based selection reflects a
      sequence of hierarchically ordered operations in extrastriate visual cortex, in
      which the selection based on task relevance has temporal priority over the
      selection based on the sensory similarity between input representations.

PMID- 23115168
TI  - Glutamate receptor delta2 associates with metabotropic glutamate receptor 1
      (mGluR1), protein kinase Cgamma, and canonical transient receptor potential 3 and
      regulates mGluR1-mediated synaptic transmission in cerebellar Purkinje neurons.
AB  - Cerebellar motor coordination and cerebellar Purkinje cell synaptic function
      require metabotropic glutamate receptor 1 (mGluR1, Grm1). We used an unbiased
      proteomic approach to identify protein partners for mGluR1 in cerebellum and
      discovered glutamate receptor delta2 (GluRdelta2, Grid2, GluDelta2) and protein
      kinase Cgamma (PKCgamma) as major interactors. We also found canonical transient
      receptor potential 3 (TRPC3), which is also needed for mGluR1-dependent slow
      EPSCs and motor coordination and associates with mGluR1, GluRdelta2, and
      PKCgamma. Mutation of GluRdelta2 changes subcellular fractionation of mGluR1 and
      TRPC3 to increase their surface expression. Fitting with this, mGluR1-evoked
      inward currents are increased in GluRdelta2 mutant mice. Moreover, loss of
      GluRdelta2 disrupts the time course of mGluR1-dependent synaptic transmission at
      parallel fiber-Purkinje cells synapses. Thus, GluRdelta2 is part of the mGluR1
      signaling complex needed for cerebellar synaptic function and motor coordination,
      explaining the shared cerebellar motor phenotype that manifests in mutants of the
      mGluR1 and GluRdelta2 signaling pathways.

PMID- 23115169
TI  - Millisecond precision spike timing shapes tactile perception.
AB  - In primates, the sense of touch has traditionally been considered to be a spatial
      modality, drawing an analogy to the visual system. In this view, stimuli are
      encoded in spatial patterns of activity over the sheet of receptors embedded in
      the skin. We propose that the spatial processing mode is complemented by a
      temporal one. Indeed, the transduction and processing of complex, high-frequency
      skin vibrations have been shown to play an important role in tactile texture
      perception, and the frequency composition of vibrations shapes the evoked
      percept. Mechanoreceptive afferents innervating the glabrous skin exhibit
      temporal patterning in their responses, but the importance and behavioral
      relevance of spike timing, particularly for naturalistic stimuli, remains to be
      elucidated. Based on neurophysiological recordings from Rhesus macaques, we show
      that spike timing conveys information about the frequency composition of skin
      vibrations, both for individual afferents and for afferent populations, and that
      the temporal fidelity varies across afferent class. Furthermore, the perception
      of skin vibrations, measured in human subjects, is better predicted when spike
      timing is taken into account, and the resolution that predicts perception best
      matches the optimal resolution of the respective afferent classes. In light of
      these results, the peripheral representation of complex skin vibrations draws a
      powerful analogy with the auditory and vibrissal systems.

PMID- 23115170
TI  - Regulation of neuronal excitability by interaction of fragile X mental
      retardation protein with slack potassium channels.
AB  - Loss of the RNA-binding protein fragile X mental retardation protein (FMRP)
      represents the most common form of inherited intellectual disability. Studies
      with heterologous expression systems indicate that FMRP interacts directly with
      Slack Na(+)-activated K(+) channels (K(Na)), producing an enhancement of channel
      activity. We have now used Aplysia bag cell (BC) neurons, which regulate
      reproductive behaviors, to examine the effects of Slack and FMRP on excitability.
      FMRP and Slack immunoreactivity were colocalized at the periphery of isolated BC
      neurons, and the two proteins could be reciprocally coimmunoprecipitated.
      Intracellular injection of FMRP lacking its mRNA binding domain rapidly induced a
      biphasic outward current, with an early transient tetrodotoxin-sensitive
      component followed by a slowly activating sustained component. The properties of
      this current matched that of the native Slack potassium current, which was
      identified using an siRNA approach. Addition of FMRP to inside-out patches
      containing native Aplysia Slack channels increased channel opening and, in
      current-clamp recordings, produced narrowing of action potentials. Suppression of
      Slack expression did not alter the ability of BC neurons to undergo a
      characteristic prolonged discharge in response to synaptic stimulation, but
      prevented recovery from a prolonged inhibitory period that normally follows the
      discharge. Recovery from the inhibited period was also inhibited by the protein
      synthesis inhibitor anisomycin. Our studies indicate that, in BC neurons, Slack
      channels are required for prolonged changes in neuronal excitability that require
      new protein synthesis, and raise the possibility that channel-FMRP interactions
      may link changes in neuronal firing to changes in protein translation.

PMID- 23115171
TI  - Localized calcineurin confers Ca2+-dependent inactivation on neuronal L-type Ca2+
      channels.
AB  - Excitation-driven entry of Ca(2+) through L-type voltage-gated Ca(2+) channels
      controls gene expression in neurons and a variety of fundamental activities in
      other kinds of excitable cells. The probability of opening of Ca(V)1.2 L-type
      channels is subject to pronounced enhancement by cAMP-dependent protein kinase
      (PKA), which is scaffolded to Ca(V)1.2 channels by A-kinase anchoring proteins
      (AKAPs). Ca(V)1.2 channels also undergo negative autoregulation via Ca(2+)
      dependent inactivation (CDI), which strongly limits Ca(2+) entry. An abundance of
      evidence indicates that CDI relies upon binding of Ca(2+)/calmodulin (CaM) to an
      isoleucine-glutamine motif in the carboxy tail of Ca(V)1.2 L-type channels, a
      molecular mechanism seemingly unrelated to phosphorylation-mediated channel
      enhancement. But our work reveals, in cultured hippocampal neurons and a
      heterologous expression system, that the Ca(2+)/CaM-activated phosphatase
      calcineurin (CaN) is scaffolded to Ca(V)1.2 channels by the neuronal anchoring
      protein AKAP79/150, and that overexpression of an AKAP79/150 mutant incapable of
      binding CaN (DeltaPIX; CaN-binding PXIXIT motif deleted) impedes CDI.
      Interventions that suppress CaN activity-mutation in its catalytic site,
      antagonism with cyclosporine A or FK506, or intracellular perfusion with a
      peptide mimicking the sequence of the phosphatase's autoinhibitory domain
      interfere with normal CDI. In cultured hippocampal neurons from a DeltaPIX knock
      in mouse, CDI is absent. Results of experiments with the adenylyl cyclase
      stimulator forskolin and with the PKA inhibitor PKI suggest that Ca(2+)/CaM
      activated CaN promotes CDI by reversing channel enhancement effectuated by
      kinases such as PKA. Hence, our investigation of AKAP79/150-anchored CaN
      reconciles the CaM-based model of CDI with an earlier, seemingly contradictory
      model based on dephosphorylation signaling.

PMID- 23115172
TI  - Multisensory representation of frequency across audition and touch: high density
      electrical mapping reveals early sensory-perceptual coupling.
AB  - The frequency of environmental vibrations is sampled by two of the major sensory
      systems, audition and touch, notwithstanding that these signals are transduced
      through very different physical media and entirely separate sensory epithelia.
      Psychophysical studies have shown that manipulating frequency in audition or
      touch can have a significant cross-sensory impact on perceived frequency in the
      other sensory system, pointing to intimate links between these senses during
      computation of frequency. In this regard, the frequency of a vibratory event can
      be thought of as a multisensory perceptual construct. In turn,
      electrophysiological studies point to temporally early multisensory interactions
      that occur in hierarchically early sensory regions where convergent inputs from
      the auditory and somatosensory systems are to be found. A key question pertains
      to the level of processing at which the multisensory integration of featural
      information, such as frequency, occurs. Do the sensory systems calculate
      frequency independently before this information is combined, or is this feature
      calculated in an integrated fashion during preattentive sensory processing? The
      well characterized mismatch negativity, an electrophysiological response that
      indexes preattentive detection of a change within the context of a regular
      pattern of stimulation, served as our dependent measure. High-density
      electrophysiological recordings were made in humans while they were presented
      with separate blocks of somatosensory, auditory, and audio-somatosensory
      "standards" and "deviants," where the deviant differed in frequency. Multisensory
      effects were identified beginning at ~200 ms, with the multisensory mismatch
      negativity (MMN) significantly different from the sum of the unisensory MMNs.
      This provides compelling evidence for preattentive coupling between the
      somatosensory and auditory channels in the cortical representation of frequency.

PMID- 23115173
TI  - Predictive and feedback performance errors are signaled in the simple spike
      discharge of individual Purkinje cells.
AB  - The cerebellum has been implicated in processing motor errors required for on
      line control of movement and motor learning. The dominant view is that Purkinje
      cell complex spike discharge signals motor errors. This study investigated
      whether errors are encoded in the simple spike discharge of Purkinje cells in
      monkeys trained to manually track a pseudorandomly moving target. Four task error
      signals were evaluated based on cursor movement relative to target movement.
      Linear regression analyses based on firing residuals ensured that the modulation
      with a specific error parameter was independent of the other error parameters and
      kinematics. The results demonstrate that simple spike firing in lobules IV-VI is
      significantly correlated with position, distance, and directional errors.
      Independent of the error signals, the same Purkinje cells encode kinematics. The
      strongest error modulation occurs at feedback timing. However, in 72% of cells at
      least one of the R(2) temporal profiles resulting from regressing firing with
      individual errors exhibit two peak R(2) values. For these bimodal profiles, the
      first peak is at a negative tau (lead) and a second peak at a positive tau (lag),
      implying that Purkinje cells encode both prediction and feedback about an error.
      For the majority of the bimodal profiles, the signs of the regression
      coefficients or preferred directions reverse at the times of the peaks. The sign
      reversal results in opposing simple spike modulation for the predictive and
      feedback components. Dual error representations may provide the signals needed to
      generate sensory prediction errors used to update a forward internal model.

PMID- 23115174
TI  - On the anticipatory precue activity in motor cortex.
AB  - Motor cortical neurons are activated during movement preparation and execution,
      and in response to task-relevant visual cues. A few studies also report
      activation before the expected presentation of cues. Here, we study specifically
      this anticipatory activity preceding visual cues in motor cortical areas. We
      recorded the activity of 1215 neurons in the motor cortex of two macaque monkeys
      while they performed a center-out reaching task, including two consecutive delays
      of equal duration, known in advance. During the first delay (D1), they had to
      await the spatial cue and only reach to the cued target after the second delay
      (D2). Forty-two percent of the neurons displayed anticipatory activity during D1.
      Among these anticipatory neurons, 59% increased (D1up) their activity and the
      remaining decreased (D1down) their activity. By classifying the neurons according
      to these firing rate profiles during D1, we found that the activity during D2
      differed in a systematic way. The D1up neurons were more likely to discharge
      phasically soon after the spatial cue and were less active during movement
      execution, whereas the D1down neurons showed the opposite pattern. But,
      regardless of their temporal activity profiles, the two categories seemed equally
      involved in early and late motor preparation, as reflected in their directional
      selectivity. This precue activity in motor cortex may reflect two complementary,
      coexisting processes: the facilitation of incoming spatial information in
      parallel with the downregulation of corticospinal excitability to prevent a
      premature response.

PMID- 23115175
TI  - Leptin regulates dopamine responses to sustained stress in humans.
AB  - Neural systems that identify and respond to salient stimuli are critical for
      survival in a complex and changing environment. In addition, interindividual
      differences, including genetic variation and hormonal and metabolic status likely
      influence the behavioral strategies and neuronal responses to environmental
      challenges. Here, we examined the relationship between leptin allelic variation
      and plasma leptin levels with DAD2/3R availability in vivo as measured with
      [(11)C]raclopride PET at baseline and during a standardized pain stress
      challenge. Allelic variation in the leptin gene was associated with varying
      levels of dopamine release in response to the pain stressor, but not with
      baseline D2/3 receptor availability. Circulating leptin was also positively
      associated with stress-induced dopamine release. These results show that leptin
      serves as a regulator of neuronal function in humans and provides an etiological
      mechanism for differences in dopamine neurotransmission in response to salient
      stimuli as related to metabolic function. The capacity for leptin to influence
      stress-induced dopaminergic function is of importance for pathological states
      where dopamine is thought to play an integral role, such as mood, substance-use
      disorders, eating disorders, and obesity.

PMID- 23115177
TI  - Thalamus-derived molecules promote survival and dendritic growth of developing
      cortical neurons.
AB  - The mammalian neocortex is composed of various types of neurons that reflect its
      laminar and area structures. It has been suggested that not only intrinsic but
      also afferent-derived extrinsic factors are involved in neuronal differentiation
      during development. However, the role and molecular mechanism of such extrinsic
      factors are almost unknown. Here, we attempted to identify molecules that are
      expressed in the thalamus and affect cortical cell development. First, thalamus
      specific molecules were sought by comparing gene expression profiles of the
      developing rat thalamus and cortex using microarrays, and by constructing a
      thalamus-enriched subtraction cDNA library. A systematic screening by in situ
      hybridization showed that several genes encoding extracellular molecules were
      strongly expressed in sensory thalamic nuclei. Exogenous and endogenous protein
      localization further demonstrated that two extracellular molecules, Neuritin-1
      (NRN1) and VGF, were transported to thalamic axon terminals. Application of NRN1
      and VGF to dissociated cell culture promoted the dendritic growth. An organotypic
      slice culture experiment further showed that the number of primary dendrites in
      multipolar stellate neurons increased in response to NRN1 and VGF, whereas
      dendritic growth of pyramidal neurons was not promoted. These molecules also
      increased neuronal survival of multipolar neurons. Taken together, these results
      suggest that the thalamus-specific molecules NRN1 and VGF play an important role
      in the dendritic growth and survival of cortical neurons in a cell type-specific
      manner.

PMID- 23115176
TI  - Axon sorting within the spinal cord marginal zone via Robo-mediated inhibition of
      N-cadherin controls spinocerebellar tract formation.
AB  - The axons of spinal projection neurons transmit sensory information to the brain
      by ascending within highly organized longitudinal tracts. However, the molecular
      mechanisms that control the sorting of these axons within the spinal cord and
      their directed growth to poorly defined targets are not understood. Here, we show
      that an interplay between Robo and the cell adhesion molecule, N-cadherin, sorts
      spinal commissural axons into appropriate longitudinal tracts within the spinal
      cord, and thereby facilitates their brain targeting. Specifically, we show that
      d1 and d2 spinal commissural axons join the lateral funiculus within the spinal
      cord and target the cerebellum in chick embryos, and that these axons contribute
      to the spinocerebellar projection in transgenic reporter mice. Disabling Robo
      signaling or overexpressing N-cadherin on these axons prevents the formation of
      the lateral funiculus and the spinocerebellar tract, and simultaneously
      perturbing Robo and N-cadherin function rescues both phenotypes in chick embryos.
      Consistent with these observations, disabling Robo function in conditional N
      cadherin knock-out mice results in a wild-type-like lateral funiculus. Together,
      these findings suggest that spinal projection axons must be sorted into distinct
      longitudinal tracts within the spinal cord proper to project to their brain
      targets.

PMID- 23115178
TI  - The impact of the posterior parietal and dorsolateral prefrontal cortices on the
      optimization of long-term versus immediate value.
AB  - fMRI research suggests that both the posterior parietal cortex (PPC) and
      dorsolateral prefrontal cortex (DLPFC) help individuals select better long-term
      monetary gains during intertemporal choice. Previous neuromodulation research has
      demonstrated that disruption of the DLPFC interferes with this ability. However,
      it is unclear whether the PPC performs a similarly important function during
      intertemporal choice, and whether the functions performed by either region impact
      choices involving losses. In the current study, we used low-frequency repetitive
      transcranial magnetic stimulation to examine whether the PPC and DLPFC both
      normally facilitate selection of gains and losses with better long-term value
      than alternatives during intertemporal choice. We found that disruption of either
      region in the right hemisphere led to greater selection of both gains and losses
      that had better immediate, but worse long-term value than alternatives. This
      indicates that activity in both regions helps individuals optimize long-term
      value relative to immediate value in general, rather than being specific to
      choices involving gains. However, there were slightly different patterns of
      effects following disruption of the right PPC and right DLPFC, suggesting that
      each region may perform somewhat different functions that help optimize choice.

PMID- 23115179
TI  - Variable sequencing is actively maintained in a well learned motor skill.
AB  - Variation in sequencing of actions occurs in many natural behaviors, yet how such
      variation is maintained is poorly understood. We investigated maintenance of
      sequence variation in adult Bengalese finch song, a learned skill with rendition
      to-rendition variation in the sequencing of discrete syllables (i.e., syllable
      "b" might transition to "c" with 70% probability and to "d" with 30%
      probability). We found that probabilities of transitions ordinarily remain stable
      but could be modified by delivering aversive noise bursts following one
      transition (e.g., "b->c") but not the alternative (e.g., "b->d"). Such
      differential reinforcement induced gradual, adaptive decreases in probabilities
      of targeted transitions and compensatory increases in alternative transitions.
      Thus, the normal stability of transition probabilities does not reflect hardwired
      premotor circuitry. While all variable transitions could be modified by
      differential reinforcement, some were less readily modified than others; these
      were cases that exhibited more alternation between possible transitions than
      predicted by chance (i.e., "b->d " would tend to follow "b->c " and vice versa).
      These history-dependent transitions were less modifiable than more stochastic
      transitions. Similarly, highly stereotyped transitions (which are completely
      predictable) were not modifiable. This suggests that stochastically generated
      variability is crucial for sequence modification. Finally, we found that, when
      reinforcement ceased, birds gradually restored transition probabilities to their
      baseline values. Hence, the nervous system retains a representation of baseline
      probabilities and has the impetus to restore them. Together, our results indicate
      that variable sequencing in a motor skill can reflect an end point of learning
      that is stably maintained via continual self-monitoring.

PMID- 23115180
TI  - A novel BACHD transgenic rat exhibits characteristic neuropathological features
      of Huntington disease.
AB  - Huntington disease (HD) is an inherited progressive neurodegenerative disorder,
      characterized by motor, cognitive, and psychiatric deficits as well as
      neurodegeneration and brain atrophy beginning in the striatum and the cortex and
      extending to other subcortical brain regions. The genetic cause is an expansion
      of the CAG repeat stretch in the HTT gene encoding huntingtin protein (htt).
      Here, we generated an HD transgenic rat model using a human bacterial artificial
      chromosome (BAC), which contains the full-length HTT genomic sequence with 97
      CAG/CAA repeats and all regulatory elements. BACHD transgenic rats display a
      robust, early onset and progressive HD-like phenotype including motor deficits
      and anxiety-related symptoms. In contrast to BAC and yeast artificial chromosome
      HD mouse models that express full-length mutant huntingtin, BACHD rats do not
      exhibit an increased body weight. Neuropathologically, the distribution of
      neuropil aggregates and nuclear accumulation of N-terminal mutant huntingtin in
      BACHD rats is similar to the observations in human HD brains. Aggregates occur
      more frequently in the cortex than in the striatum and neuropil aggregates appear
      earlier than mutant htt accumulation in the nucleus. Furthermore, we found an
      imbalance in the striatal striosome and matrix compartments in early stages of
      the disease. In addition, reduced dopamine receptor binding was detectable by in
      vivo imaging. Our data demonstrate that this transgenic BACHD rat line may be a
      valuable model for further understanding the disease mechanisms and for
      preclinical pharmacological studies.

PMID- 23115181
TI  - Modulation of CGRP-induced light aversion in wild-type mice by a 5-HT(1B/D)
      agonist.
AB  - The neuropeptide calcitonin gene-related peptide (CGRP) plays a critical role in
      the pathophysiology of migraine. We have focused on the role of CGRP in
      photophobia, which is a common migraine symptom. We previously used an operant
      based assay to show that CGRP-sensitized transgenic (nestin/hRAMP1), but not
      control, mice exhibited light aversion in response to an intracerebroventricular
      CGRP injection. A key question was whether the transgenic phenotype was due to
      overexpression of the CGRP receptor at endogenous or novel expression sites. We
      reasoned that if endogenous receptor sites were sufficient for light-aversive
      behavior, then wild-type mice should also show the phenotype when given a
      sufficiently strong stimulus. In this study, we report that mice with normal
      levels of endogenous CGRP receptors demonstrate light avoidance following CGRP
      administration. This phenotype required the combination of two factors: higher
      light intensity and habituation to the testing chamber. Control tests confirmed
      that light aversion was dependent on coincident exposure to CGRP and light and
      cannot be fully explained by increased anxiety. Furthermore, CGRP reduced
      locomotion only in the dark, not in the light. Coadministration of rizatriptan, a
      5-HT(1B/D) agonist anti-migraine drug, attenuated the effects of exogenous CGRP
      on light aversion and motility. This suggests that triptans can act by mechanisms
      that are distinct from inhibition of CGRP release. Thus, we demonstrate that
      activation of endogenous CGRP receptors is sufficient to elicit light aversion in
      mice, which can be modulated by a drug commonly used to treat migraine.

PMID- 23115182
TI  - Irrational choice under uncertainty correlates with lower striatal D(2/3)
      receptor binding in rats.
AB  - Individual differences in dopamine (DA) signaling, including low striatal D(2/3)
      receptors, may increase vulnerability to substance abuse, although whether this
      phenotype confers susceptibility to nonchemical addictions is unclear. The degree
      to which people use "irrational" cognitive heuristics when choosing under
      uncertainty can determine whether they find gambling addictive. Given that
      dopaminergic projections to the striatum signal reward expectancy and modulate
      decision-making, individual differences in DA signaling could influence the
      extent of such biases. To test this hypothesis, we used a novel task to model
      biased, risk-averse decision-making in rats. Animals chose between a "safe"
      lever, which guaranteed delivery of the wager, or an "uncertain" lever, which
      delivered either double the wager or nothing with 50:50 odds. The bet size varied
      from one to three sugar pellets. Although the amount at stake did not alter the
      options' utility, a subgroup of "wager-sensitive" rats increased their preference
      for the safe lever as the bet size increased, akin to risk aversion. In contrast,
      wager-insensitive rats slightly preferred the uncertain option consistently.
      Amphetamine increased choice of the uncertain option in wager-sensitive, but not
      in wager-insensitive rats, whereas a D(2/3) receptor antagonist decreased
      uncertain lever choice in wager-insensitive rats alone. Micro-PET and
      autoradiography using [(11)C]raclopride confirmed a strong correlation between
      high wager sensitivity and low striatal D(2/3) receptor density. These data
      suggest that the propensity for biased decision-making under uncertainty is
      influenced by striatal D(2/3) receptor expression, and provide novel support for
      the hypothesis that susceptibility to chemical and behavioral addictions may
      share a common neurobiological basis.

PMID- 23115183
TI  - The dynamic nature of top-down signals originating from prefrontal cortex: a
      combined fMRI-TMS study.
AB  - The prefrontal cortex (PFC) is proposed to be the source of top-down signals that
      can modulate extrastriate visual processing in accordance with behavioral goals,
      yet little direct causal evidence for this hypothesis exists. Using theta burst
      transcranial magnetic stimulation, we disrupted PFC function in human
      participants before performing a working memory task during fMRI scanning. PFC
      disruption decreased the tuning of extrastriate cortex responses, coinciding with
      decrements in working memory performance. We also found that activity in the
      homologous PFC region in the nonstimulated hemisphere predicted performance
      following disruption. Specifically, those participants with greater homologous
      PFC activity and greater connectivity between this region and extrastriate cortex
      were the most resistant to PFC disruption. These findings provide evidence for a
      compensatory mechanism following insults to the brain, and insight into the
      dynamic nature of top-down signals originating from the PFC.

PMID- 23115184
TI  - Regulation of motor representation by phase-amplitude coupling in the
      sensorimotor cortex.
AB  - High-gamma amplitude (80-150 Hz) represents motor information, such as movement
      types, on the sensorimotor cortex. In several cortical areas, high-gamma
      amplitudes are coupled with low-frequency phases, e.g., alpha and theta (phase
      amplitude coupling, PAC). However, such coupling has not been studied in the
      sensorimotor cortex; thus, its potential functional role has yet to be explored.
      We investigated PAC of high-gamma amplitude in the sensorimotor cortex during
      waiting for and the execution of movements using electrocorticographic (ECoG)
      recordings in humans. ECoG signals were recorded from the sensorimotor cortices
      of 4 epilepsy patients while they performed three different hand movements. A
      subset of electrodes showed high-gamma activity selective to movement type around
      the timing of motor execution, while the same electrodes showed nonselective high
      gamma activity during the waiting period (>2 s before execution). Cross frequency
      coupling analysis revealed that the high-gamma amplitude during waiting was
      strongly coupled with the alpha phase (10-14 Hz) at the electrodes with movement
      selective high-gamma amplitudes during execution. This coupling constituted the
      high-gamma amplitude peaking around the trough of the alpha oscillation, and its
      strength and phase were not predictive of movement type. As the coupling
      attenuated toward the timing of motor execution, the high-gamma amplitude
      appeared to be released from the alpha phase to build a motor representation with
      phase-independent activity. Our results suggest that PAC modulates motor
      representation in the sensorimotor cortex by holding and releasing high-gamma
      activity in movement-selective cortical regions.

PMID- 23115185
TI  - Oxytocin promotes long-term potentiation by enhancing epidermal growth factor
      receptor-mediated local translation of protein kinase Mzeta.
AB  - In addition to triggering the birthing process and milk release, the hypothalamic
      neuropeptide oxytocin (OXT) plays an important role in the regulation of complex
      social cognition and behavior. Previous work has shown that OXT can regulate
      hippocampal synaptic plasticity and improve hippocampus-dependent cognitive
      functions in the female mice, but the underlying mechanisms remain largely
      unclear. Here, we demonstrate that OXT promotes the maintenance of long-term
      potentiation (LTP) induced by one train of tetanic stimulation (TS) in the CA1
      region of hippocampal slices from both nulliparous female and male rats through a
      previously unknown mechanism involving OXT receptor (OXTR)-dependent and
      epidermal growth factor receptor (EGFR)-mediated local translation of an atypical
      protein kinase C isoform, protein kinase Mzeta (PKMzeta), in dendrites. Using
      pharmacological and biochemical approaches, we show that both the conventional
      OXTR-associated signaling pathway (G(q/11)-coupled phospholipase C) and the
      transactivated EGFR downstream signaling pathways (phosphatidylinositol 3 kinase
      and extracellular signal-regulated kinase 1/2) are involved in the regulation of
      OXT. In addition, OXT stimulates local dendritic PKMzeta mRNA translation via
      activation of a mammalian target of rapamycin-regulated mechanism. Furthermore,
      blockade of OXTR results in a modest decrease in the ability to maintain late
      phase LTP induced by three trains of TS. These results reveal a novel OXTR-to
      EGFR communication to regulate the new synthesis of PKMzeta, which functions to
      promote the maintenance of LTP at hippocampal CA1 synapses.

PMID- 23115186
TI  - Adaptation of spike timing precision controls the sensitivity to interaural time
      difference in the avian auditory brainstem.
AB  - While adaptation is widely thought to facilitate neural coding, the form of
      adaptation should depend on how the signals are encoded. Monaural neurons early
      in the interaural time difference (ITD) pathway encode the phase of sound input
      using spike timing rather than firing rate. Such neurons in chicken nucleus
      magnocellularis (NM) adapt to ongoing stimuli by increasing firing rate and
      decreasing spike timing precision. We measured NM neuron responses while adapting
      them to simulated physiological input, and used these responses to construct
      inputs to binaural coincidence detector neurons in nucleus laminaris (NL).
      Adaptation of spike timing in NM reduced ITD sensitivity in NL, demonstrating the
      dominant role of timing in the short-term plasticity as well as the immediate
      response of this sound localization circuit.

PMID- 23115187
TI  - Trk activation of the ERK1/2 kinase pathway stimulates intermediate chain
      phosphorylation and recruits cytoplasmic dynein to signaling endosomes for
      retrograde axonal transport.
AB  - The retrograde transport of Trk-containing endosomes from the axon to the cell
      body by cytoplasmic dynein is necessary for axonal and neuronal survival. We
      investigated the recruitment of dynein to signaling endosomes in rat embryonic
      neurons and PC12 cells. We identified a novel phosphoserine on the dynein
      intermediate chains (ICs), and we observed a time-dependent neurotrophin
      stimulated increase in intermediate chain phosphorylation on this site in both
      cell types. Pharmacological studies, overexpression of constitutively active MAP
      kinase kinase, and an in vitro assay with recombinant proteins demonstrated that
      the intermediate chains are phosphorylated by the MAP kinase ERK1/2,
      extracellular signal-regulated kinase, a major downstream effector of Trk. Live
      cell imaging with fluorescently tagged IC mutants demonstrated that the
      dephosphomimic mutants had significantly reduced colocalization with Trk and
      Rab7, but not a mitochondrial marker. The phosphorylated intermediate chains were
      enriched on immunoaffinity-purified Trk-containing organelles. Inhibition of ERK
      reduced the amount of phospho-IC and the total amount of dynein that copurified
      with the signaling endosomes. In addition, inhibition of ERK1/2 reduced the
      motility of Rab7- and TrkB-containing endosomes and the extent of their
      colocalization with dynein in axons. NGF-dependent survival of sympathetic
      neurons was significantly reduced by the overexpression of the dephosphomimic
      mutant IC-1B-S80A, but not WT IC-1B, further demonstrating the functional
      significance of phosphorylation on this site. These results demonstrate that
      neurotrophin binding to Trk initiates the recruitment of cytoplasmic dynein to
      signaling endosomes through ERK1/2 phosphorylation of intermediate chains for
      their subsequent retrograde transport in axons.

PMID- 23115188
TI  - Loss of signal transducer and activator of transcription 3 (STAT3) signaling
      during elevated activity causes vulnerability in hippocampal neurons.
AB  - Chronically altered levels of network activity lead to changes in the morphology
      and functions of neurons. However, little is known of how changes in neuronal
      activity alter the intracellular signaling pathways mediating neuronal survival.
      Here, we use primary cultures of rat hippocampal neurons to show that elevated
      neuronal activity impairs phosphorylation of the serine/threonine kinase, Erk1/2,
      and the activation of signal transducer and activator of transcription 3 (STAT3)
      by phosphorylation of serine 727. Chronically stimulated neurons go through
      apoptosis when they fail to activate another serine/threonine kinase, Akt. Gain-
      and loss-of-function experiments show that STAT3 plays the key role directly
      downstream from Erk1/2 as the alternative survival pathway. Elevated neuronal
      activity resulted in increased expression of a tumor suppressor, p53, and its
      target gene, Bax. These changes are observed in Kv4.2 knock-out mouse hippocampal
      neurons, which are also sensitive to the blockade of TrkB signaling, confirming
      that the alteration occurs in vivo. Thus, this study provides new insight into a
      mechanism by which chronic elevation of activity may cause neurodegeneration.

PMID- 23115189
TI  - Neuroprotective effects of reactive oxygen species mediated by BDNF-independent
      activation of TrkB.
AB  - Reactive oxygen species (ROS) have diverse biological consequences in the
      mammalian CNS, but the molecular targets mediating these pleiotropic effects are
      incompletely understood. Like ROS, the neurotrophin receptor, TrkB receptor
      tyrosine kinase, has diverse effects in the developing and mature mammalian
      brain. Our discovery that zinc can transactivate TrkB, together with the finding
      that ROS can trigger zinc release from cytosolic zinc binding proteins, led us to
      hypothesize that ROS can transactivate TrkB in CNS neurons by a zinc-dependent
      mechanism. We found that both exogenous H(2)O(2) and endogenous ROS activate TrkB
      signaling by a Src family kinase-dependent but brain-derived neurotrophic factor
      independent mechanism in cultured rat cortical neurons. Exogenous H(2)O(2)
      enhances cytosolic zinc content in a metallothionein-3 (MT-3)-requiring manner.
      Both exogenous H(2)O(2) and endogenous ROS mediated transactivation of TrkB
      requires intracellular zinc and MT-3. The ROS-triggered transactivation of TrkB
      exerts neuroprotective effects, because inhibition of TrkB kinase activity or
      uncoupling Shc signaling from TrkB exacerbates neuronal cell death induced by
      H(2)O(2). Thus, we propose a molecular signaling event whereby ROS induce release
      of zinc from cytosolic MT-3, the increased cytosolic zinc transactivates TrkB,
      and the enhanced Shc signaling downstream from TrkB promotes prosurvival effects.
      We suggest that such neuroprotective effects mediated by ROS are operative in
      diverse acute and chronic neurological disorders.

PMID- 23115190
TI  - Cerebellar ataxia by enhanced Ca(V)2.1 currents is alleviated by Ca2+-dependent
      K+-channel activators in Cacna1a(S218L) mutant mice.
AB  - Mutations in the CACNA1A gene are associated with neurological disorders, such as
      ataxia, hemiplegic migraine, and epilepsy. These mutations affect the pore
      forming alpha(1A)-subunit of Ca(V)2.1 channels and thereby either decrease or
      increase neuronal Ca(2+) influx. A decreased Ca(V)2.1-mediated Ca(2+) influx has
      been shown to reduce the regularity of cerebellar Purkinje cell activity and to
      induce episodic cerebellar ataxia. However, little is known about how ataxia can
      be caused by CACNA1A mutations that increase the Ca(2+) influx, such as the S218L
      missense mutation. Here, we demonstrate that the S218L mutation causes a negative
      shift of voltage dependence of Ca(V)2.1 channels of mouse Purkinje cells and
      results in lowered thresholds for somatic action potentials and dendritic Ca(2+)
      spikes and in disrupted firing patterns. The hyperexcitability of Cacna1a(S218L)
      Purkinje cells was counteracted by application of the activators of Ca(2+)
      dependent K(+) channels, 1-EBIO and chlorzoxazone (CHZ). Moreover, 1-EBIO also
      alleviated the irregularity of Purkinje cell firing both in vitro and in vivo,
      while CHZ improved the irregularity of Purkinje cell firing in vitro as well as
      the motor performance of Cacna1a(S218L) mutant mice. The current data suggest
      that abnormalities in Purkinje cell firing contributes to cerebellar ataxia
      induced by the S218L mutation and they advocate a general therapeutic approach in
      that targeting Ca(2+)-dependent K(+) channels may be beneficial for treating
      ataxia not only in patients suffering from a decreased Ca(2+) influx, but also in
      those suffering from an increased Ca(2+) influx in their Purkinje cells.

PMID- 23115191
TI  - Tis21 knock-out enhances the frequency of medulloblastoma in Patched1
      heterozygous mice by inhibiting the Cxcl3-dependent migration of cerebellar
      neurons.
AB  - A failure in the control of proliferation of cerebellar granule neuron precursor
      cells (GCPs), located in the external granular layer (EGL) of the cerebellum,
      gives rise to medulloblastoma. To investigate the process of neoplastic
      transformation of GCPs, we generated a new medulloblastoma model by crossing
      Patched1 heterozygous mice, which develop medulloblastomas with low frequency,
      with mice lacking the Tis21 gene. Overexpression of Tis21 is known to inhibit
      proliferation and trigger differentiation of GCPs; its expression decreases in
      human medulloblastomas. Double-knock-out mice show a striking increase in the
      frequency of medulloblastomas and hyperplastic EGL lesions, formed by
      preneoplastic GCPs. Tis21 deletion does not affect the proliferation of GCPs but
      inhibits their differentiation and, chiefly, their intrinsic ability to migrate
      outside the EGL. This defect of migration may represent an important step in
      medulloblastoma formation, as GCPs, remaining longer in the EGL proliferative
      niche, may become more prone to transformation. By genome-wide analysis, we
      identified the chemokine Cxcl3 as a target of Tis21. Cxcl3 is downregulated in
      Tis21-null GCPs of EGL and lesions; addition of Cxcl3 to cerebellar slices
      rescues the defective migration of Tis21-null GCPs and, remarkably, reduces the
      area of hyperplastic lesions. As Tis21 activates Cxcl3 transcription, our results
      suggest that Tis21 induces migration of GCPs through Cxcl3, which may represent a
      novel target for medulloblastoma therapy.

PMID- 23115193
TI  - Interplay between sniffing and odorant sorptive properties in the rat.
AB  - For decades it has been known that the olfactory sensory epithelium can act like
      a chromatograph, separating odorants based on their air-mucus sorptive properties
      (Mozell and Jagodowicz, 1973). It has been hypothesized that animals could take
      advantage of this property, modulating sniffing behavior to manipulate airflow
      and thereby directing odorant molecules to the portions of the olfactory
      epithelium where they are best detected (Schoenfeld and Cleland, 2005). We report
      here a test of this hypothesis in behaving rats, monitoring respiratory activity
      through diaphragm electromyogram, which allowed us to estimate nasal airflow. In
      our test rats had to detect either low-sorption (LS) or high-sorption (HS)
      monomolecular odorant targets from the same stimulus set of six binary odor
      mixtures. We found that it is more difficult for rats to detect LS than HS
      targets. Although sniffing bouts are the same duration for each group (~500 ms),
      sniffing longer and using more inhalations results in better performance for rats
      assigned to detect LS targets. LS-detecting rats also increase the duration of
      individual inhalations (81 ms for LS- vs 69 ms for HS-detecting rats) and sniff
      at lower frequencies (7.8 Hz for LS- vs 8.6 Hz for HS-detecting rats) when
      learning to sense the target. When LS-detecting rats do discriminate well, they
      do so with lower airflow, more sniffs, and lower frequency of sniffing than HS
      detecting counterparts. These data show that rats adjust sniff strategies as a
      function of odorant sorptiveness and provide support for the chromatographic and
      zonation hypotheses.

PMID- 23115192
TI  - Appoptosin is a novel pro-apoptotic protein and mediates cell death in
      neurodegeneration.
AB  - Apoptosis is an essential cellular process in multiple diseases and a major
      pathway for neuronal death in neurodegeneration. The detailed signaling
      events/pathways leading to apoptosis, especially in neurons, require further
      elucidation. Here we identify a beta-amyloid precursor protein (APP)-interacting
      protein, designated as appoptosin, whose levels are upregulated in brain samples
      from Alzheimer's disease and infarct patients, and in rodent stroke models, as
      well as in neurons treated with beta-amyloid (Abeta) and glutamate. We further
      demonstrate that appoptosin induces reactive oxygen species release and intrinsic
      caspase-dependent apoptosis. The physiological function of appoptosin is to
      transport/exchange glycine/5-amino-levulinic acid across the mitochondrial
      membrane for heme synthesis. Downregulation of appoptosin prevents cell death and
      caspase activation caused by glutamate or Abeta insults. APP modulates appoptosin
      mediated apoptosis through interaction with appoptosin. Our study identifies
      appoptosin as a crucial player in apoptosis and a novel pro-apoptotic protein
      involved in neuronal cell death, providing a possible new therapeutic target for
      neurodegenerative disorders.

PMID- 23115194
TI  - Seizure-induced neuronal death is suppressed in the absence of the endogenous
      lectin Galectin-1.
AB  - Pilocarpine injection induces epileptic seizures in rodents, an experimental
      paradigm extensively used to model temporal lobe epilepsy in humans. It includes
      conspicuous neuronal death in the forebrain and previous work has demonstrated an
      involvement of the neurotrophin receptor p75(NTR) in this process. Following the
      identification of Galectin-1 (Gal-1) as a downstream effector of p75(NTR), we
      examine here the role of this endogenous lectin in pilocarpine-induced cell death
      in adult mice. We found that most somatostatin-positive neurons also express Gal
      1 and that in mice lacking the corresponding gene Lgals1, pilocarpine-induced
      neuronal death was essentially abolished in the forebrain. We also found that the
      related lectin Galectin-3 (Gal-3) was strongly upregulated by pilocarpine in
      microglial cells. This upregulation was absent in Lgals1 mutants and our results
      with Lgals3-null animals show that Gal-3 is not required for neuronal death in
      the hippocampus. These findings provide new insights into the roles and
      regulation of endogenous lectins in the adult CNS and a surprisingly selective
      proapoptotic role of Gal-1 for a subpopulation of GABAergic interneurons.

PMID- 23115195
TI  - Cognitive-affective neural plasticity following active-controlled mindfulness
      intervention.
AB  - Mindfulness meditation is a set of attention-based, regulatory, and self-inquiry
      training regimes. Although the impact of mindfulness training (MT) on self
      regulation is well established, the neural mechanisms supporting such plasticity
      are poorly understood. MT is thought to act through interoceptive salience and
      attentional control mechanisms, but until now conflicting evidence from
      behavioral and neural measures renders difficult distinguishing their respective
      roles. To resolve this question we conducted a fully randomized 6 week
      longitudinal trial of MT, explicitly controlling for cognitive and treatment
      effects with an active-control group. We measured behavioral metacognition and
      whole-brain blood oxygenation level-dependent (BOLD) signals using functional MRI
      during an affective Stroop task before and after intervention in healthy human
      subjects. Although both groups improved significantly on a response-inhibition
      task, only the MT group showed reduced affective Stroop conflict. Moreover, the
      MT group displayed greater dorsolateral prefrontal cortex responses during
      executive processing, consistent with increased recruitment of top-down
      mechanisms to resolve conflict. In contrast, we did not observe overall group-by
      time interactions on negative affect-related reaction times or BOLD responses.
      However, only participants with the greatest amount of MT practice showed
      improvements in response inhibition and increased recruitment of dorsal anterior
      cingulate cortex, medial prefrontal cortex, and right anterior insula during
      negative valence processing. Our findings highlight the importance of active
      control in MT research, indicate unique neural mechanisms for progressive stages
      of mindfulness training, and suggest that optimal application of MT may differ
      depending on context, contrary to a one-size-fits-all approach.

PMID- 23115196
TI  - The anterior cingulate cortex may enhance inhibition of lateral prefrontal cortex
      via m2 cholinergic receptors at dual synaptic sites.
AB  - The anterior cingulate cortex (ACC) and dorsolateral prefrontal cortices (DLPFC)
      share robust excitatory connections. However, during rapid eye movement (REM)
      sleep, when cortical activity is dominated by acetylcholine, the ACC is activated
      but DLPFC is suppressed. Using pathway tracing and electron microscopy in
      nonhuman primates (Macaca mulatta), we tested the hypothesis that the opposite
      states may reflect specific modulation by acetylcholine through strategic
      synaptic localization of muscarinic m2 receptors, which inhibit neurotransmitter
      release presynaptically, but are thought to be excitatory postsynaptically. In
      the ACC pathway to DLPFC (area 32 to area 9), m2 receptors predominated in ACC
      axon terminals and in more than half of the targeted dendrites of presumed
      inhibitory neurons, suggesting inhibitory cholinergic influence. In contrast, in
      a pathway linking the DLPFC area 46 to DLPFC area 9, postsynaptic m2 receptors
      predominated in targeted spines of presumed excitatory neurons, consistent with
      their mutual activation in working memory. These novel findings suggest that
      presynaptic and postsynaptic specificity of m2 cholinergic receptors may help
      explain the differential engagement of ACC and DLPFC areas in REM sleep for
      memory consolidation and synergism in awake states for cognitive control.

PMID- 23115197
TI  - The signature of maternal rearing in the methylome in rhesus macaque prefrontal
      cortex and T cells.
AB  - Early-life adversity is associated with a broad scope of life-long health and
      behavioral disorders. Particularly critical is the role of the mother. A possible
      mechanism is that these effects are mediated by "epigenetic" mechanisms. Studies
      in rodents suggest a causal relationship between early-life adversity and changes
      in DNA methylation in several "candidate genes" in the brain. This study examines
      whether randomized differential rearing (maternal vs surrogate-peer rearing) of
      rhesus macaques is associated with differential methylation in early adulthood.
      The data presented here show that differential rearing leads to differential DNA
      methylation in both prefrontal cortex and T cells. These differentially
      methylated promoters tend to cluster by both chromosomal region and gene
      function. The broad impact of maternal rearing on DNA methylation in both the
      brain and T cells supports the hypothesis that the response to early-life
      adversity is system-wide and genome-wide and persists to adulthood. Our data also
      point to the feasibility of studying the impact of the social environment in
      peripheral T-cell DNA methylation.

PMID- 23115198
TI  - Finding NECA: zebrafish screen identifies key signalling pathway in beta-cell
      regeneration.

PMID- 23115199
TI  - Lactate-starved neurons in ALS.

PMID- 23115200
TI  - Synergy in science: an interview with Neal Copeland and Nancy Jenkins.
      Interviewed by Sarah Allan.

PMID- 23115201
TI  - Do stroke models model stroke?
AB  - Stroke is one of the leading causes of death worldwide and the biggest reason for
      long-term disability. Basic research has formed the modern understanding of
      stroke pathophysiology, and has revealed important molecular, cellular and
      systemic mechanisms. However, despite decades of research, most translational
      stroke trials that aim to introduce basic research findings into clinical
      treatment strategies - most notably in the field of neuroprotection - have
      failed. Among other obstacles, poor methodological and statistical standards,
      negative publication bias, and incomplete preclinical testing have been proposed
      as 'translational roadblocks'. In this article, we introduce the models commonly
      used in preclinical stroke research, discuss some of the causes of failed
      translational success and review potential remedies. We further introduce the
      concept of modeling 'care' of stroke patients, because current preclinical
      research models the disorder but does not model care or state-of-the-art clinical
      testing. Stringent statistical methods and controlled preclinical trials have
      been suggested to counteract weaknesses in preclinical research. We conclude that
      preclinical stroke research requires (1) appropriate modeling of the disorder,
      (2) appropriate modeling of the care of stroke patients and (3) an approach to
      preclinical testing that is similar to clinical testing, including Phase 3
      randomized controlled preclinical trials as necessary additional steps before new
      therapies enter clinical testing.

PMID- 23115202
TI  - Zebrafish models flex their muscles to shed light on muscular dystrophies.
AB  - Muscular dystrophies are a group of genetic disorders that specifically affect
      skeletal muscle and are characterized by progressive muscle degeneration and
      weakening. To develop therapies and treatments for these diseases, a better
      understanding of the molecular basis of muscular dystrophies is required. Thus,
      identification of causative genes mutated in specific disorders and the study of
      relevant animal models are imperative. Zebrafish genetic models of human muscle
      disorders often closely resemble disease pathogenesis, and the optical clarity of
      zebrafish embryos and larvae enables visualization of dynamic molecular processes
      in vivo. As an adjunct tool, morpholino studies provide insight into the
      molecular function of genes and allow rapid assessment of candidate genes for
      human muscular dystrophies. This unique set of attributes makes the zebrafish
      model system particularly valuable for the study of muscle diseases. This review
      discusses how recent research using zebrafish has shed light on the pathological
      basis of muscular dystrophies, with particular focus on the muscle cell membrane
      and the linkage between the myofibre cytoskeleton and the extracellular matrix.

PMID- 23115203
TI  - Preclinical research in Rett syndrome: setting the foundation for translational
      success.
AB  - In September of 2011, the National Institute of Neurological Disorders and Stroke
      (NINDS), the Eunice Kennedy Shriver National Institute of Child Health and Human
      Development (NICHD), the International Rett Syndrome Foundation (IRSF) and the
      Rett Syndrome Research Trust (RSRT) convened a workshop involving a broad cross
      section of basic scientists, clinicians and representatives from the National
      Institutes of Health (NIH), the US Food and Drug Administration (FDA), the
      pharmaceutical industry and private foundations to assess the state of the art in
      animal studies of Rett syndrome (RTT). The aim of the workshop was to identify
      crucial knowledge gaps and to suggest scientific priorities and best practices
      for the use of animal models in preclinical evaluation of potential new RTT
      therapeutics. This review summarizes outcomes from the workshop and extensive
      follow-up discussions among participants, and includes: (1) a comprehensive
      summary of the physiological and behavioral phenotypes of RTT mouse models to
      date, and areas in which further phenotypic analyses are required to enhance the
      utility of these models for translational studies; (2) discussion of the impact
      of genetic differences among mouse models, and methodological differences among
      laboratories, on the expression and analysis, respectively, of phenotypic traits;
      and (3) definitions of the standards that the community of RTT researchers can
      implement for rigorous preclinical study design and transparent reporting to
      ensure that decisions to initiate costly clinical trials are grounded in reliable
      preclinical data.

PMID- 23115206
TI  - Imaging markers offer promise: dream enactment may predict your patient's future.

PMID- 23115205
TI  - Understanding the hypoxic niche of multiple myeloma: therapeutic implications and
      contributions of mouse models.
AB  - Multiple myeloma (MM) is the second most common hematological malignancy and is
      characterized by the clonal expansion of plasma cells in the bone marrow.
      Recently, hypoxia has received increased interest in the context of MM, in both
      basic and translational research. In this review, we describe the discovery of
      the hypoxic niche in MM and how it can be targeted therapeutically. We also
      discuss mouse models that closely mimic human MM, highlighting those that allow
      preclinical research into new therapies that exploit the hypoxic niche in MM.

PMID- 23115204
TI  - Fibrodysplasia ossificans progressiva: mechanisms and models of skeletal
      metamorphosis.
AB  - Fibrodysplasia ossificans progressiva (FOP; MIM #135100) is a debilitating
      genetic disorder of connective tissue metamorphosis. It is characterized by
      malformation of the great (big) toes during embryonic skeletal development and by
      progressive heterotopic endochondral ossification (HEO) postnatally, which leads
      to the formation of a second skeleton of heterotopic bone. Individuals with these
      classic clinical features of FOP have the identical heterozygous activating
      mutation (c.617G>A; R206H) in the gene encoding ACVR1 (also known as ALK2), a
      bone morphogenetic protein (BMP) type I receptor. Disease activity caused by this
      ACVR1 mutation also depends on altered cell and tissue physiology that can be
      best understood in the context of a high-fidelity animal model. Recently, we
      developed such a knock-in mouse model for FOP (Acvr1(R206H/+)) that recapitulates
      the human disease, and provides a valuable new tool for testing and developing
      effective therapies. The FOP knock-in mouse and other models in Drosophila,
      zebrafish, chickens and mice provide an arsenal of tools for understanding BMP
      signaling and addressing outstanding questions of disease mechanisms that are
      relevant not only to FOP but also to a wide variety of disorders associated with
      regenerative medicine and tissue metamorphosis.

PMID- 23115207
TI  - A 66-year-old patient with vanishing white matter disease due to the p.Ala87Val
      EIF2B3 mutation.
AB  - Vanishing white matter (VWM; OMIM # 603896) is one of the most prevalent
      inherited childhood leukoencephalopathies. It has, however, become evident that
      VWM has a wider clinical spectrum, with age at onset inversely related to
      clinical severity. Many affected women experience a combination of
      leukoencephalopathy and primary amenorrhea or premature ovarian failure, a
      condition named ovarioleukodystrophy. Mutations in any of the genes encoding the
      5 subunits of the Eukaryotic Initiation Factor 2B gene (EIF2B1, 2, 3, 4, and 5)
      can independently cause VWM.(1).

PMID- 23115208
TI  - Migraine headache is present in the aura phase: a prospective study.
AB  - OBJECTIVES: Migraine aura is commonly considered to be a distinct phase of a
      migraine attack that precedes headache. The objective of the study was to examine
      a large number of prospectively recorded attacks of migraine with aura and
      determine the timing of headache and other migraine symptoms relative to aura.
      METHODS: As part of a clinical trial we collected prospective data on the time
      course of headache and other symptoms relative to the aura. Patients (n = 267)
      were enrolled from 16 centers, and asked to keep a headache diary for 1 month
      (phase I). They were asked to record headache symptoms as soon as possible after
      aura began and always within 1 hour of aura onset. A total of 456 attacks were
      reported during phase I by 201 patients. These patients were then randomized and
      included in phase II, during which a total of 405 attacks were reported in 164
      patients. In total, we present data from 861 attacks of migraine with aura from
      201 patients. RESULTS: During the aura phase, the majority of attacks (73%) were
      associated with headache. Other migraine symptoms were also frequently reported
      during the aura: nausea (51%), photophobia (88%), and photophobia (73%). During
      the first 15 minutes within the onset of aura, 54% of patients reported headache
      fulfilling the criteria for migraine. CONCLUSION: Our results indicate that
      headaches as well as associated migraine symptoms are present early, during the
      aura phase of the migraine attack in the majority of patients.

PMID- 23115209
TI  - Dysfunction of the neuromuscular junction in spinal muscular atrophy types 2 and
      3.
AB  - OBJECTIVE: Spinal muscular atrophy (SMA) is pathologically characterized by
      degeneration of anterior horn cells. Recent observations in animal models of SMA
      and muscle tissue from patients with SMA suggest additional abnormalities in the
      development and maturation of the neuromuscular junction. We therefore evaluated
      neuromuscular junction function in SMA with repetitive nerve stimulation.
      METHODS: In this case-control study, repetitive nerve stimulation was performed
      in 35 patients with SMA types 2, 3, and 4, 20 healthy controls, and 5 controls
      with motor neuron disease. RESULTS: Pathologic decremental responses (>10%)
      during 3-Hz repetitive nerve stimulation were observed in 17 of 35 patients (49%)
      with SMA types 2 and 3, but not in healthy controls or controls with motor neuron
      disease. None of the patients or controls had an abnormal incremental response of
      >60%. The presence of an abnormal decremental response was not specific for the
      type of SMA, nor was it associated with compound muscle action potential
      amplitude, clinical scores, or disease duration. Two of 4 patients with SMA type
      3 who tried pyridostigmine reported increased stamina. CONCLUSIONS: These data
      suggest dysfunction of the neuromuscular junction in patients with SMA types 2
      and 3. Therefore, drugs that facilitate neuromuscular transmission are candidate
      drugs for evaluation in carefully designed, placebo-controlled, clinical trials.

PMID- 23115210
TI  - Cerebral small-vessel disease and progression of brain atrophy: the SMART-MR
      study.
AB  - OBJECTIVES: To investigate whether severity and progression of periventricular
      and deep white matter lesions (WML) and lacunar infarcts were associated with
      progression of brain atrophy. METHODS: Within the SMART-MR study, a prospective
      cohort on MRI changes in patients with symptomatic atherosclerotic disease, 565
      patients (57 +/- 9 years) without large infarcts had vascular screening and 1.5 T
      MRI at baseline and after a mean follow-up of 3.9 years. With automated brain
      segmentation, total brain, cortical gray matter, ventricular, and WML volumes
      were estimated and expressed relative to intracranial volume (%). Lacunar
      infarcts were rated manually. RESULTS: Using linear regression analyses adjusted
      for demographics and vascular risk factors, periventricular WML volume at
      baseline was associated with greater decrease in cortical gray matter volume (B =
      -1.73%, 95% confidence interval [CI] -3.15% to -0.30%, per 1% WML volume
      increase) and greater increase in ventricular volume (B = 0.12%, 95% CI 0.04% to
      0.20%). Progression of periventricular WML volume corresponded with a greater
      decrease in cortical gray matter volume (B = -0.45%, 95% CI -0.9% to 0%) and
      greater increase in ventricular volume (B = 0.15%, 95% CI 0.1% to 0.2%). Presence
      of lacunar infarcts was associated with greater decline in total brain volume (B
      = -0.25%, 95% CI -0.49% to -0.01%) and progression of lacunar infarcts with a
      greater decrease of total brain (B = -0.30%, 95% CI -0.59% to 0.01%) and cortical
      gray matter volume (B = -0.81%, 95% CI -1.43% to -0.20%). CONCLUSIONS: In
      patients with symptomatic atherosclerotic disease, presence and progression of
      periventricular WML and lacunar infarcts is associated with greater progression
      of brain atrophy independent of vascular risk factors.

PMID- 23115211
TI  - Adherence to antihypertensive agents after ischemic stroke and risk of
      cardiovascular outcomes.
AB  - OBJECTIVE: To evaluate the relationship between antihypertensive (AH) drug
      adherence and cardiovascular (CV) outcomes among patients with a recent ischemic
      stroke and assess the validity of our approach. METHODS: A cohort of 14,227
      patients diagnosed with an ischemic stroke was assembled from individuals 65
      years and older who were treated with AH agents from 1999 to 2007 in Quebec,
      Canada. A nested case-control design was used to evaluate the occurrence of
      nonfatal major CV outcomes and mortality. Each case was matched to 15 controls by
      age and cohort entry time. Medication possession ratio was used for AH agent
      adherence level. Adjusted conditional logistic regression models were used to
      estimate the rate ratio of CV events. The validity of the approach was assessed
      by evaluating the adherence level of CV-protective and non-CV-protective drugs.
      RESULTS: Mean age was 75 years, 54% were male, 38% had coronary artery disease,
      23% had diabetes, 47% dyslipidemia, and 14% atrial fibrillation or flutter. High
      adherence to AH therapy was mirrored by similar adherence to statins and
      antiplatelet agents and was associated with a lower risk of nonfatal vascular
      events compared with lower adherence (rate ratio 0.77 [0.70-0.86]). We observed a
      paradoxic link between adherence to several drugs and all-cause mortality.
      CONCLUSION: Adherence to AH agents is associated with adherence to other
      secondary preventive therapies and a risk reduction for nonfatal vascular events
      after an ischemic stroke. Overestimation of all-cause mortality reduction may be
      related to frailty and comorbidities, which may confound the apparent benefit of
      different drugs.

PMID- 23115212
TI  - Video game-based coordinative training improves ataxia in children with
      degenerative ataxia.
AB  - OBJECTIVE: Degenerative ataxias in children present a rare condition where
      effective treatments are lacking. Intensive coordinative training based on
      physiotherapeutic exercises improves degenerative ataxia in adults, but such
      exercises have drawbacks for children, often including a lack of motivation for
      high-frequent physiotherapy. Recently developed whole-body controlled video game
      technology might present a novel treatment strategy for highly interactive and
      motivational coordinative training for children with degenerative ataxias.
      METHODS: We examined the effectiveness of an 8-week coordinative training for 10
      children with progressive spinocerebellar ataxia. Training was based on 3
      Microsoft Xbox Kinect video games particularly suitable to exercise whole-body
      coordination and dynamic balance. Training was started with a laboratory-based 2
      week training phase and followed by 6 weeks training in children's home
      environment. Rater-blinded assessments were performed 2 weeks before laboratory
      based training, immediately prior to and after the laboratory-based training
      period, as well as after home training. These assessments allowed for an
      intraindividual control design, where performance changes with and without
      training were compared. RESULTS: Ataxia symptoms were significantly reduced
      (decrease in Scale for the Assessment and Rating of Ataxia score, p = 0.0078) and
      balance capacities improved (dynamic gait index, p = 0.04) after intervention.
      Quantitative movement analysis revealed improvements in gait (lateral sway: p =
      0.01; step length variability: p = 0.01) and in goal-directed leg placement (p =
      0.03). CONCLUSIONS: Despite progressive cerebellar degeneration, children are
      able to improve motor performance by intensive coordination training. Directed
      training of whole-body controlled video games might present a highly
      motivational, cost-efficient, and home-based rehabilitation strategy to train
      dynamic balance and interaction with dynamic environments in a large variety of
      young-onset neurologic conditions. CLASSIFICATION OF EVIDENCE: This study
      provides Class III evidence that directed training with Xbox Kinect video games
      can improve several signs of ataxia in adolescents with progressive ataxia as
      measured by SARA score, Dynamic Gait Index, and Activity-specific Balance
      Confidence Scale at 8 weeks of training.

PMID- 23115213
TI  - PML-IRIS in a patient treated with brentuximab.
AB  - A 38-year-old woman was diagnosed with cutaneous anaplastic T-cell lymphoma that
      proved refractory to methotrexate, bexarotene, denileukin diftitox, interferon
      gamma-1b, interferon alpha-2b, vorinostat, and pralatrexate. She was therefore
      started on the newly approved monoclonal anti-CD30 antibody brentuximab vedotin.
      Treatment with brentuximab 1.8 mg/kg IV every 3 weeks quickly led to
      disappearance of her cutaneous tumors. The day after her second brentuximab
      infusion she developed word-finding difficulties and unsteady gait. Due to
      further neurologic deterioration, she was admitted to an outside hospital. Brain
      MRI revealed multifocal enhancing white matter lesions throughout bilateral
      cerebral hemispheres and posterior fossa (figure, A-C). Brain biopsy was
      performed 15 days after her last brentuximab dose to rule out metastases and she
      was diagnosed with progressive multifocal leukoencephalopathy (PML) (figure, J).
      The patient was discharged home with hospice care. Upon discharge, she was
      started on prednisone 50 mg daily to help treat her eczema. Her family brought
      her to our clinic for a second opinion.

PMID- 23115214
TI  - Hippocampal perfusion predicts impending neurodegeneration in REM sleep behavior
      disorder.
AB  - OBJECTIVES: Patients with idiopathic REM sleep behavior disorder (IRBD) are at
      risk for developing Parkinson disease (PD) and dementia with Lewy bodies (DLB).
      We aimed to identify functional brain imaging patterns predicting the emergence
      of PD and DLB in patients with IRBD, using SPECT with (99m)Tc-ethylene cysteinate
      dimer (ECD). METHODS: Twenty patients with IRBD were scanned at baseline during
      wakefulness using (99m)Tc-ECD SPECT. After a follow-up of 3 years on average,
      patients were divided into 2 groups according to whether or not they developed
      defined neurodegenerative disease (PD, DLB). SPECT data analysis comparing
      regional cerebral blood flow (rCBF) between groups assessed whether specific
      brain perfusion patterns were associated with subsequent clinical evolution.
      Regression analysis between rCBF and clinical markers of neurodegeneration
      (motor, color vision, olfaction) looked for neural structures involved in this
      process. RESULTS: Of the 20 patients with IRBD recruited for this study, 10
      converted to PD or DLB during the follow-up. rCBF at baseline was increased in
      the hippocampus of patients who would later convert compared with those who would
      not (p < 0.05 corrected). Hippocampal perfusion was correlated with motor and
      color vision scores across all IRBD patients. CONCLUSIONS: (99m)Tc-ECD SPECT
      identifies patients with IRBD at risk for conversion to other neurodegenerative
      disorders such as PD or DLB; disease progression in IRBD is predicted by abnormal
      perfusion in the hippocampus at baseline. Perfusion within this structure is
      correlated with clinical markers of neurodegeneration, further suggesting its
      involvement in the development of presumed synucleinopathies.

PMID- 23115215
TI  - Feature-based effects in the coupling between attention and saccades.
AB  - Previous research has demonstrated that prior to saccade execution visual
      attention is imperatively shifted towards the saccade target (e.g., Deubel &
      Schneider, 1996; Kowler, Anderson, Dosher, & Blaser, 1995). Typically, observers
      had to make a saccade according to an arrow cue and simultaneously perform a
      perceptual discrimination task either at the saccade endpoint or elsewhere on the
      screen. Discrimination performance was poor if the location of the saccade target
      (ST) and the discrimination target (DT) did not coincide. However, those
      experiments only investigated shifts of spatial attention. In the current
      experiments, we examined how feature-based attention is deployed before a
      saccade. In Experiment 1, we randomly varied the colors of the ST and DT. Results
      showed that discrimination performance was better when the DT was shown in the
      same color as the ST. This color congruency effect was slightly larger and more
      reliable when ST color was relevant and constant across trials (Experiment 2). We
      conclude that selection of a colored ST can induce display-wide facilitative
      processing of stimuli sharing this color. Results are discussed in terms of
      saccade programming and saccade selection, color priming in visual search, color
      cuing, and color-based top-down contingent attentional capture. We also discuss
      basic mechanisms of spatial- and feature-based attention and predictive remapping
      of visual information across saccades.

PMID- 23115216
TI  - Contribution of nonattentive motion to object tracking.
AB  - Object tracking has been generally discussed in relation to attention, but it is
      quite possible that nonattentive low-level motion components are involved. To
      elucidate this issue, we examined temporal aspects of object tracking by using
      stimuli comprised of just a single attribute and those comprised of multiple
      attributes. High-level motion processes supposedly can process cross-attribute
      motion, while nonattentive low-level motion processes cannot handle such motion.
      In Experiment 1, we measured the upper temporal limits for within- and cross
      attribute object tracking, using stimuli defined by several different attributes
      (luminance, motion, binocular disparity, flicker, and contrast). It was found
      that the temporal limits with within-attribute stimuli (4-5 Hz) were much higher
      than those with cross-attribute stimuli (2-3 Hz). These results suggest that
      mechanisms involved in within- and cross-attribute object tracking are partially
      different. We conducted two additional experiments to clarify the nature of this
      difference. In Experiment 2, we measured the temporal limits for classical
      apparent motion perception using the same stimulus combinations as for Experiment
      1. The temporal limits with within- and cross-attribute stimuli were both between
      4 and 5 Hz. These values corresponded to those of within-attribute object
      tracking but were faster than those of cross-attribute object tracking. In
      Experiment 3, we measured the temporal limit for voluntary shifts of attention
      that did not involve motion. Temporal limits quite similar to those for cross
      attribute object tracking (2-3 Hz) were obtained. These results suggest that
      nonattentive motion mechanisms are involved in within-attribute object tracking,
      whereas attention-based mechanisms mediate cross-attribute object tracking.

PMID- 23115217
TI  - Interocular suppression in normal and amblyopic vision: spatio-temporal
      properties.
AB  - We measured the properties of interocular suppression in strabismic amblyopes and
      compared these to dichoptic masking in binocularly normal observers. We used a
      dichoptic version of the well-established probed-sinewave paradigm that measured
      sensitivity to a brief target stimulus (one of four letters to be discriminated)
      in the amblyopic eye at different times relative to a suppression-inducing mask
      in the fixing eye. This was done using both sinusoidal steady state and transient
      approaches. The suppression-inducing masks were either modulations of luminance
      or contrast (full field, just overlaying the target, or just surrounding the
      target). Our results were interpreted using a descriptive model that included
      contrast gain control and spatio-temporal filtering prior to excitatory binocular
      combination. The suppression we measured, other than in magnitude, was not
      fundamentally different from normal dichoptic masking: lowpass spatio-temporal
      properties with similar contributions from both surround and overlay suppression.

PMID- 23115218
TI  - Spotting expertise in the eyes: billiards knowledge as revealed by gaze shifts in
      a dynamic visual prediction task.
AB  - In sports, as in other activities and knowledge domains, expertise is a highly
      valuable asset. We assessed whether expertise in billiards is associated with
      specific patterns of eye movements in a visual prediction task. Professional
      players and novices were presented a number of simplified billiard shots on a
      computer screen, previously filmed in a real set, with the last part of the ball
      trajectory occluded. They had to predict whether or not the ball would have hit
      the central skittle. Experts performed better than novices, in terms of both
      accuracy and response time. By analyzing eye movements, we found that during
      occlusion, experts rarely extrapolated with the gaze the occluded part of the
      ball trajectory-a behavior that was widely diffused in novices-even when the
      unseen path was long and with two bounces interposed. Rather, they looked
      selectively at specific diagnostic points on the cushions along the ball's
      visible trajectory, in accordance with a formal metrical system used by
      professional players to calculate the shot coordinates. Thus, the eye movements
      of expert observers contained a clear signature of billiard expertise and
      documented empirically a strategy upgrade in visual problem solving from dynamic,
      analog simulation in imagery to more efficient rule-based, conceptual knowledge.

PMID- 23115219
TI  - Impulse control, diabetes-specific self-efficacy, and diabetes management among
      emerging adults with type 1 diabetes.
AB  - OBJECTIVE: To explore the relationships among impulse control, diabetes-specific
      self-efficacy, and diabetes management behaviors among emerging adults with type
      1 diabetes. METHODS: A total of 204 high school seniors (M = 18.25 years, SD =
      .45, 55.9% females) with type 1 diabetes self-reported on impulse control,
      diabetes-specific self-efficacy, and diabetes management behaviors during the
      past 3 months. Mediation and path analyses were used to address aims. RESULTS:
      Greater impulse control was associated with better diabetes management among
      these emerging adults. In addition, diabetes-specific self-efficacy partially
      mediated the relationship between impulse control and diabetes management.
      CONCLUSIONS: Impulse control and diabetes-specific self-efficacy may be important
      in the management of type 1 diabetes among emerging adults. Diabetes-specific
      self-efficacy may play an important role in successful diabetes management among
      youth with lower impulse control.

PMID- 23115220
TI  - Systems pharmacological analysis of paclitaxel-mediated tumor priming that
      enhances nanocarrier deposition and efficacy.
AB  - Paclitaxel (PAC)-mediated apoptosis decompresses and primes tumors for enhanced
      deposition of nanoparticulate agents such as pegylated liposomal doxorubicin
      (DXR). A quantitative pharmacokinetic/pharmacodynamic (PK/PD) approach was
      developed to analyze efficacy and identify optima for PAC combined with
      sterically stabilized liposome (SSL)-DXR. Using data extracted from diverse
      literature sources, Cremophor-paclitaxel (Taxol((r))) PK was described by a
      carrier-mediated dispositional model and SSL-DXR PK was described by a two
      compartment model with first-order drug release. A hybrid-physiologic, well
      stirred model with partition coefficients (Kp) captured intratumor
      concentrations. Apoptotic responses driving tumor priming were modeled using
      nonlinear, time-dependent transduction functions. The tumor growth model used net
      first-order growth and death rate constants, and two transit compartments that
      captured the temporal displacement of tumor exposure versus effect, and apoptotic
      signals from each agent were used to drive cytotoxic effects of the combination.
      The final model captured plasma and intratumor PK data, apoptosis induction
      profiles, and tumor growth for all treatments/sequences. A feedback loop
      representing PAC-induced apoptosis effects on Kp(_DXR) enabled the model to
      capture tumor-priming effects. Simulations to explore time- and sequence
      dependent effects of priming indicated that PAC priming increased K(p_DXR) 3
      fold. The intratumor concentrations producing maximal and half-maximal effects
      were 18 and 7.2 MUg/ml for PAC, and 17.6 and 14.3 MUg/ml for SSL-DXR. The
      duration of drug-induced apoptosis was 27.4 h for PAC and 15.8 h for SSL-DXR.
      Simulations suggested that PAC administered 24 h before peak priming could
      increase efficacy 2.5-fold over experimentally reported results. The quantitative
      approach developed in this article is applicable for evaluating tumor-priming
      strategies using diverse agents.

PMID- 23115221
TI  - Novel insights on the effect of nicotine in a murine colitis model.
AB  - Studies showed that nicotine has a positive influence on symptoms of ulcerative
      colitis. In the present study, we explored the effect of nicotine treatment using
      different routes of administration in the dextran sodium sulfate (DSS) colitis
      mouse model. We also investigated the effects of cotinine, a major metabolite of
      nicotine, in the model. C57BL6 adult male mice were given DSS solution freely in
      the drinking water for seven consecutive days, and tap water was given
      thereafter. Disease severity, length of the colon, colon tissue histology, and
      inflammatory markers, including colonic myeloperoxidase activity and colonic
      tumor necrosis factor-alpha levels, were evaluated. The effect of nicotine and
      cotinine treatments via various different routes of administration were examined
      the DSS model. In addition, we measured the plasma levels of nicotine and
      cotinine in our treatment protocols. Administration of low, but not high, doses
      of oral nicotine in DSS-treated mice resulted in a significant decrease in
      disease severity, histologic damage scores, as well as colonic level of tumor
      necrosis factor-alpha. However, the anti-inflammatory effect of nicotine was not
      seen after chronic s.c. or minipump infusion of the drug. Differences in plasma
      levels of nicotine and cotinine do not seem to account for this lack of effect.
      Finally, oral cotinine alone failed to show a significant effect in the DSS model
      of colitis. These results highlight that dose and route of administration play a
      critical role in the protective effect of nicotine in the DSS mouse colitis
      model.

PMID- 23115223
TI  - Continuous and extended infusions of beta-lactam antibiotics in the pediatric
      population.
AB  - OBJECTIVE: To conduct a systematic review of available data on the use of
      extended or continuous infusion of beta-lactam and monobactam therapy in the
      pediatric population (aged 0-18 years). DATA SOURCES: A literature search was
      performed using PubMed (1975-May 2012), International Pharmaceutical Abstracts
      (1970-May 2012), and Web of Science (1977-May 2012) to identify studies for
      inclusion. In addition, reference citations from identified publications were
      reviewed. The following search terms were used: pediatric, children, neonate,
      infant, adolescent, beta-lactam, cephalosporin, carbapenem, penicillin,
      monobactam, continuous infusion, extended infusion, and/or prolonged infusion.
      Individual names of drugs in each class of antibiotics were also included in the
      search. STUDY SELECTION AND DATA EXTRACTION: Randomized controlled clinical
      trials, pharmacokinetic/pharmacodynamic studies, observational studies, and case
      reports involving pediatric patients who received extended or continuous infusion
      of beta-lactam or monobactam antibiotics were reviewed. Only English-language
      publications were included. DATA SYNTHESIS: One randomized controlled clinical
      trial, 5 pharmacokinetic studies, 2 pharmacodynamic studies using Monte Carlo
      simulation, 1 case series, and 7 case reports were included in the analysis. The
      cephalosporin class has been studied the most and currently represents the only
      clinical trial using a continuous infusion dosing strategy in pediatric patients.
      There is limited clinical evidence available to support the use of extended or
      continuous infusion of beta-lactam antibiotics in the pediatric population.
      Pharmacodynamic studies conducted in this population mirror the current evidence
      in adults for cefepime and meropenem. The single prospective clinical trial using
      continuous infusion of ceftazidime failed to demonstrate any clinical benefit
      over traditional dosing; however, there was equal efficacy. CONCLUSIONS: More
      well-designed prospective clinical trials are required to determine the role of
      extended or continuous infusion of beta-lactam antibiotics in treatment of
      pediatric patients.

PMID- 23115222
TI  - The antinociceptive effects of nicotinic receptors alpha7-positive allosteric
      modulators in murine acute and tonic pain models.
AB  - The alpha7 nicotinic acetylcholine receptor (nAChR) subtype is abundantly
      expressed in the central nervous system and in the periphery. Recent evidence
      suggests that alpha7 nAChR subtypes, which can be activated by an endogenous
      cholinergic tone, comprising acetylcholine and the alpha7 nAChR agonist choline,
      play an important role in subchronic pain and inflammation. This study's
      objective was to test whether alpha7 nAChR positive allosteric modulators (PAMs)
      produce antinociception in in vivo mouse models of acute and persistent pain.
      Testing type I [N-(5-chloro-2-hydroxyphenyl)-N'-[2-chloro-5
      (trifluoromethyl)phenyl] (NS1738)] and type II [1-(5-chloro-2,4-dimethoxy-phenyl)
      3-(5-methyl-isoxazol-3-yl) (PNU-120596)] alpha7 nAChR PAMs in acute and
      persistent pain, we found that, although neither reduced acute thermal pain, only
      PNU-120596 dose-dependently attenuated paw-licking behavior in the formalin test.
      The long-acting effect of PNU-120596 in this test was in discordance with its
      pharmacokinetic profile in mice, which suggests the involvement of postreceptor
      signaling mechanisms. Our results with selective mitogen-activated protein kinase
      kinase inhibitor 1,4-diamino-2,3-dicyano-1,4-bis(o-aminophenylmercapto)butadiene
      monoethanolate (U0126) argues for an important role of extracellular signal
      regulated kinase-1/2 pathways activation in PNU-120596's antinociceptive effects.
      The alpha7 antagonist MLA, administered intrathecally, reversed PNU-120596's
      effects, confirming PNU-120596's action, in part, through central alpha7 nAChRs.
      Importantly, tolerance to PNU-120596 was not developed after subchronic treatment
      of the drug. Surprisingly, PNU-120596's antinociceptive effects were blocked by
      NS1738. Our results indicate that type II alpha7 nAChR PAM PNU-120596, but not
      type I alpha7 nAChR PAM NS1738, shows significant antinociception effects in
      persistent pain models in mice.

PMID- 23115224
TI  - Evaluation of vitamin B12 monitoring in a veteran population on long-term, high
      dose metformin therapy.
AB  - BACKGROUND: Metformin can result in vitamin B(12) deficiency, potentially leading
      to complications such as neuropathy. Annual monitoring of vitamin B(12) has been
      suggested; however, it is unknown whether current practice reflects this
      recommendation. OBJECTIVE: To identify vitamin B(12) monitoring patterns in
      patients on long-term, high-dose metformin. Secondary objective was to determine
      the frequency of new vitamin B(12) deficiency, anemia, and neuropathy documented
      after initiation of high-dose metformin. METHODS: Electronic medical records of
      veterans treated at the Veterans Affairs Maryland Healthcare System with high
      dose metformin (>=2000 mg/day) as of November 1, 2010, were reviewed. Data
      regarding metformin treatment, vitamin B(12) measurements, and documentation of
      vitamin B(12) deficiency, cyanocobalamin supplementation, anemia, and neuropathy
      were collected. Subjects treated with metformin for less than 1 year or those
      with documented peripheral neuropathy, megaloblastic anemia, vitamin B(12)
      deficiency, or a condition associated with vitamin B(12) malabsorption prior to
      metformin initiation were excluded. RESULTS: Subjects (N = 235) had a mean
      metformin dose of 2050 mg/day and mean duration of treatment of 5.2 years. Sixty
      percent did not have vitamin B(12) measured. Of subjects receiving metformin for
      10 years or more, nearly half (46%) never had vitamin B(12) measured. New
      documentation of vitamin B(12) deficiency or cyanocobalamin supplementation was
      found in 5.5% of the population, and anemia was found in 12%. Of the 14% with new
      neuropathy, 42% did not have vitamin B(12) measured. CONCLUSIONS: Vitamin B(12)
      was not routinely monitored in patients on high-dose metformin, even in those at
      highest risk (>=10 years of therapy), or in those with potential manifestations
      of vitamin B(12) deficiency (neuropathy). Cases of vitamin B(12) deficiency and
      resulting anemia or neuropathy may be undiagnosed and untreated because of lack
      of monitoring. Prospective studies examining the effect of increased vitamin
      B(12) monitoring on identification and treatment of vitamin B(12) deficiency in
      patients on metformin are warranted.

PMID- 23115225
TI  - The role of decitabine for the treatment of acute myeloid leukemia.
AB  - OBJECTIVE: To review the available literature addressing the role of decitabine
      for the treatment of acute myeloid leukemia (AML). DATA SOURCES: Relevant
      literature was identified by a PubMed search (January 1970-March 2012) of English
      language literature using the terms decitabine, acute myeloid leukemia, and DNA
      methyltransferase inhibitors. STUDY SELECTION AND DATA EXTRACTION: All published
      studies and abstracts, as well as relevant consensus guidelines, evaluating the
      current literature about the role of decitabine for the treatment of AML were
      included. DATA SYNTHESIS: Decitabine has been evaluated for the treatment of AML
      in several different settings. In patients with newly diagnosed AML who are not
      candidates for standard remission induction chemotherapy, a Phase 2 trial of
      decitabine administered for 5 days per cycle demonstrated a 24% complete
      remission rate (CR). A subsequent Phase 3 trial comparing decitabine and low-dose
      cytarabine or best supportive care in a similar patient population showed a
      greater CR rate (18% vs 8%; p = 0.001) but no overall survival benefit. A Phase 2
      trial demonstrated a 47% CR rate with decitabine initially administered for 10
      days per cycle, with subsequent doses customized to individual response and
      toxicity. This novel dosing schedule has yet to be evaluated in a Phase 3 trial.
      Decitabine is also being investigated for the treatment of relapsed/refractory
      AML and as bridge therapy to allogeneic hematopoietic stem cell transplantation.
      CONCLUSIONS: Decitabine offers a promising alternative therapeutic option for
      patients with AML who are not candidates for standard remission induction
      chemotherapy. Because of its acceptable safety profile, research is investigating
      the clinical benefit of decitabine in combination with other antileukemic
      therapies. The potential roles of decitabine in the treatment of AML continue to
      be explored in numerous clinical trials.

PMID- 23115226
TI  - Extended-release mesalamine granules for ulcerative colitis.
AB  - OBJECTIVE: To evaluate the efficacy and safety of extended-release mesalamine
      granules in the maintenance of remission in ulcerative colitis (UC). DATA
      SOURCES: Literature was obtained through searches of MEDLINE (1990-June 2012)
      using the terms mesalamine granules, ulcerative colitis, Apriso, and Salofalk.
      Bibliographies from retrieved articles were searched for additional citations.
      STUDY SELECTION AND DATA EXTRACTION: All English-language articles reporting on
      use of extended-release mesalamine granules in humans identified through the
      search were evaluated and included. DATA SYNTHESIS: The preferred initial
      treatment for induction and maintenance of remission in mild to moderate UC is
      agents from the 5-aminosalicylate class (balsalazide, mesalamine, olsalazine,
      sulfasalazine). Mesalamine granules are available as an encapsulated product in
      the US and as a nonencapsulated formulation in Europe. Data evaluating
      encapsulated mesalamine granules for induction of remission are lacking; however,
      the European mesalamine granule formulation has been evaluated for induction of
      remission. Patients receiving mesalamine granules for induction achieved clinical
      and endoscopic remission more frequently than those receiving placebo. Two
      pivotal, randomized, double-blind, placebo-controlled, multicenter studies have
      evaluated encapsulated mesalamine granules for maintenance in 562 adults in
      remission from UC. In both studies, the proportion of patients who remained
      relapse-free at 6 months was higher for those receiving encapsulated mesalamine
      granules than placebo. Mesalamine granules are well tolerated, with headache,
      nausea, and upper respiratory infections being the most frequently reported
      adverse effects. CONCLUSIONS: Current evidence supports the use of extended
      release mesalamine granules for maintenance of remission in mild to moderate UC.
      Further studies are necessary to examine the ideal dose and regimen of
      encapsulated mesalamine granules for induction of remission in UC.

PMID- 23115227
TI  - A probable interaction between warfarin and the antiretroviral TRIO study
      regimen.
AB  - OBJECTIVE: To report a probable drug interaction between the antiretroviral TRIO
      regimen (ritonavir-boosted darunavir, etravirine, and raltegravir) and warfarin
      in an HIV-infected patient. CASE SUMMARY: In January 2010, a 50-year-old
      transgender female with HIV infection and recurrent deep vein thrombosis began
      treatment with the TRIO study regimen. Treatment had been maintained with
      warfarin for the past 5 years and emtricitabine monotherapy for the preceding 22
      months. Emtricitabine was discontinued when the TRIO regimen was started. The
      mean weekly warfarin dose while the patient was receiving emtricitabine
      monotherapy was 13.3 mg (95% CI 12.7 to 13.8), with a mean international
      normalized ratio (INR) of 2.8 (95% CI 2.5 to 3.1). Following the initiation of
      the TRIO regimen, the mean weekly warfarin dose was increased to 19.3 mg (95% CI
      18.5 to 20.1) and was maintained over the ensuing 71 weeks with a mean INR of 2.6
      (95% CI 2.2 to 3.0). DISCUSSION: Information on the effect of newer
      antiretrovirals on warfarin metabolism, as well as the collective contribution of
      combination antiretroviral therapy including multiple agents that may alter
      warfarin metabolism, is limited. We predicted that warfarin dose requirements
      would change upon initiation of the TRIO regimen. Given the variability in INR
      that can occur with chronic warfarin treatment, weekly warfarin doses were
      averaged during emtricitabine monotherapy (90 weeks) and TRIO regimen (71 weeks)
      periods. Mean weekly warfarin doses increased by 45% (p < 0.001) following
      initiation of the TRIO regimen. Mean INR results for the 2 time periods were not
      significantly different, demonstrating that stable anticoagulation was
      maintained. The Horn drug interaction probability scale score to assess causation
      indicated a probable interaction. CONCLUSIONS: An increased weekly warfarin dose
      requirement is predicted when warfarin is used concurrently with the
      antiretroviral TRIO regimen. Increased INR monitoring is prudent when the
      combination is administered.

PMID- 23115228
TI  - Bevacizumab-induced oral mucositis in background of cutaneous plaque-type
      psoriasis.
AB  - OBJECTIVE: To report the serial development of oral mucositis following infusion
      of bevacizumab in a young woman with a malignant brain tumor and history of
      cutaneous psoriasis. CASE SUMMARY: A 29-year-old woman with a history of active
      cutaneous psoriasis and a malignant glioneuronal tumor was treated with
      bevacizumab for 2.5 years. With each infusion of bevacizumab, she developed oral
      mucositis within 36 hours. She received temozolomide as part of concurrent
      therapy with radiation and as maintenance therapy; it was discontinued after
      continuous therapy for 1.5 years. Bevacizumab 10 mg/kg was added after 7 cycles
      of maintenance temozolomide, as the tumor had minimal response and evidence of
      increased perfusion with angiogenesis on imaging studies. All medication,
      including temozolomide, was evaluated and eventually discontinued, with the
      exception of bevacizumab, which remained the drug suspected of causing the
      mucositis. DISCUSSION: Oral mucositis is a frequent adverse effect of cytotoxic
      chemotherapy, but has not been reported with bevacizumab. The Naranjo probability
      scale indicated a probable adverse drug reaction. This likely indicates that
      bevacizumab is one of many drugs known to induce exacerbation of psoriatic
      disease. We speculate that oral mucositis developed as bevacizumab-induced
      generation of proinflammatory cytokines within the vascular endothelium, leading
      to mucosal damage and ulceration. In addition, interruption of reparative
      angiogenic pathways with bevacizumab likely contributed to the severity of
      mucositis. CONCLUSIONS: Clinicians should be aware that bevacizumab can
      potentially exacerbate psoriatic disease.

PMID- 23115229
TI  - Use of romiplostim in a hemodialysis patient with primary immune
      thrombocytopenia.
AB  - OBJECTIVE: To present the case of a patient with primary immune thrombocytopenia
      (ITP), renal impairment, and chronic hepatitis C virus (HCV) infection who was
      treated with platelet transfusions, intravenous immunoglobulin (IVIG),
      corticosteroids, eltrombopag, rituximab, and romiplostim in an attempt to raise
      platelet counts to a clinically acceptable level. CASE SUMMARY: A 71-year-old man
      with end-stage renal disease (ESRD) was on maintenance hemodialysis and had long
      term diabetes mellitus, chronic obstructive pulmonary disease, and other
      comorbidities. He was admitted with epistaxis, severe thrombocytopenia, and a
      platelet count of 4 * 10(9)/L. Platelet transfusions, treatment with IVIG,
      corticosteroids, eltrombopag, and rituximab resulted in transient and inadequate
      increases in platelet counts. Further bleeding manifestations, including
      epistaxis, melena, hematomas, and ecchymotic patches prompted treatment with
      blood product concentrates and a higher dose of eltrombopag, resulting in a
      further lack of clinical response. After 6 weeks of failed treatment attempts,
      initiation of weekly treatment with romiplostim 5 MUg/kg resulted in rapid
      stabilization (within a week) of platelet counts in the range of 200 * 10(9)/L.
      The patient was discharged, with subsequent dose adjustment of weekly romiplostim
      treatment to 2.5 MUg/kg, continued hemodialysis, and a return to normal daily
      activities. DISCUSSION: The primary clinical concern in this elderly patient with
      multiple comorbidities was to lower the bleeding risk associated with consistent
      thrombocytopenia. Despite the lack of clinical data to support the efficacy and
      safety of romiplostim in patients with ITP and renal impairment, stimulation of
      platelet production with romiplostim was a reasonable approach in view of the
      bleeding risk and following nonresponse to treatment with corticosteroids, IVIG,
      eltrombopag, and rituximab. To our knowledge, this case represents the first
      successful use of romiplostim to manage primary ITP in the presence of ESRD and
      concurrent chronic HCV infection in a patient on hemodialysis. CONCLUSIONS:
      Romiplostim appears to be a viable option for treatment of ITP in a patient with
      ESRD and chronic HCV infection following nonresponse to treatment with
      corticosteroids, IVIG, eltrombopag, and rituximab.

PMID- 23115230
TI  - Identification and characterization of a chitin-binding protein purified from
      coelomic fluid of the lugworm Arenicola marina defining a novel protein sequence
      family.
AB  - We have isolated a novel type of lectin named Arenicola marina lectin-1 (AML-1)
      from the lugworm A. marina. The lectin was purified from the coelomic fluid by
      affinity chromatography on a GlcNAc-derivatized column and eluted with GlcNAc. On
      SDS-PAGE, AML-1 showed an apparent molecular mass of 27 and 31 kDa in the reduced
      state. The N-terminal amino acid sequences were identical in these two bands. In
      the unreduced state, a complex band pattern was observed with bands from 35 kDa
      to more than 200 kDa. Two different full-length clones encoding polypeptides of
      241 and 243 amino acids, respectively, were isolated from a coelomocyte cDNA
      library. The two clones, designated AML-1a and AML-1b, were 92% identical at the
      protein level and represent a novel type of protein sequence family. Purified AML
      1 induced agglutination of rabbit erythrocytes, which could be inhibited by N
      acetylated saccharides. Recombinant AML-1b showed the same band pattern as the
      native protein, whereas recombinant AML-1a in the reduced state lacked a 27 kDa
      band. AML-1b bound GlcNAc-derivatized columns and chitin, whereas AML-1a did not
      bind to these matrices. Immunohistochemical analysis revealed that AML-1 is
      expressed by coelomocytes in the nephridium and in round cells in the epidermis
      and in eggs. Moreover, AML-1 expression was up-regulated in response to a
      parasitic infection. We conclude that AML-1 purified from coelomic fluid is
      encoded by AML-1b and represents a novel type of protein family that binds
      acetylated components.

PMID- 23115231
TI  - Transglycosylation by chitinase D from Serratia proteamaculans improved through
      altered substrate interactions.
AB  - We describe the improvement of transglycosylation (TG) by chitinase D from
      Serratia proteamaculans (SpChiD). The SpChiD produced a smaller quantity of TG
      products for up to 90 min with 2 mm chitotetraose as the substrate and
      subsequently produced only hydrolytic products. Of the five residues targeted at
      the catalytic center, E159D resulted in substantial loss of both hydrolytic and
      TG activities. Y160A resulted in a product profile similar to SpChiD and a rapid
      turnover of substrate with slightly increased TG activity. The rest of the three
      mutants, M226A, Y228A, and R284A, displayed improved TG and decreased hydrolytic
      ability. Four of the five amino acid substitutions, F64W, F125A, G119S, and
      S116G, at the catalytic groove increased TG activity, whereas W120A completely
      lost the TG activity with a concomitant increase in hydrolysis. Mutation of Trp
      247 at the solvent-accessible region significantly reduced the hydrolytic
      activity with increased TG activity. The mutants M226A, Y228A, F125A, S116G,
      F64W, G119S, R284A, and W247A accumulated approximately double the concentration
      of TG products like chitopentaose and chitohexaose, compared with SpChiD. The
      double mutant E159D/F64W regained the activity with accumulation of 6.0%
      chitopentaose at 6 h, similar to SpChiD at 30 min. Loss of chitobiase activity
      was unique to Y228A. Substitution of amino acids at the catalytic center and/or
      groove substantially improved the TG activity of SpChiD, both in terms of the
      quantity of TG products produced and the extended duration of TG activity.

PMID- 23115232
TI  - Reduced PDZ interactions of rescued DeltaF508CFTR increases its cell surface
      mobility.
AB  - Deletion of phenylalanine 508 (DeltaF508) in the cystic fibrosis transmembrane
      conductance regulator (CFTR) plasma membrane chloride channel is the most common
      cause of cystic fibrosis (CF). Though several maneuvers can rescue endoplasmic
      reticulum-retained DeltaF508CFTR and promote its trafficking to the plasma
      membrane, rescued DeltaF508CFTR remains susceptible to quality control mechanisms
      that lead to accelerated endocytosis, ubiquitination, and lysosomal degradation.
      To investigate the role of scaffold protein interactions in rescued DeltaF508CFTR
      surface instability, the plasma membrane mobility of DeltaF508CFTR was measured
      in live cells by quantum dot single particle tracking. Following rescue by low
      temperature, chemical correctors, thapsigargin, or overexpression of GRASP55,
      DeltaF508CFTR diffusion was more rapid than that of wild-type CFTR because of
      reduced interactions with PDZ domain-containing scaffold proteins. Knock-down of
      the plasma membrane quality control proteins CHIP and Hsc70 partially restored
      DeltaF508CFTR-scaffold association. Quantitative comparisons of CFTR cell surface
      diffusion and endocytosis kinetics suggested an association between reduced
      scaffold binding and CFTR internalization. Our surface diffusion measurements in
      live cells indicate defective scaffold interactions of rescued DeltaF508CFTR at
      the cell surface, which may contribute to its defective peripheral processing.

PMID- 23115233
TI  - Electrostatic ratchet in the protective antigen channel promotes anthrax toxin
      translocation.
AB  - Central to the power-stroke and brownian-ratchet mechanisms of protein
      translocation is the process through which nonequilibrium fluctuations are
      rectified or ratcheted by the molecular motor to transport substrate proteins
      along a specific axis. We investigated the ratchet mechanism using anthrax toxin
      as a model. Anthrax toxin is a tripartite toxin comprised of the protective
      antigen (PA) component, a homooligomeric transmembrane translocase, which
      translocates two other enzyme components, lethal factor (LF) and edema factor
      (EF), into the cytosol of the host cell under the proton motive force (PMF). The
      PA-binding domains of LF and EF (LF(N) and EF(N)) possess identical folds and
      similar solution stabilities; however, EF(N) translocates ~10-200-fold slower
      than LF(N), depending on the electrical potential (Deltapsi) and chemical
      potential (DeltapH) compositions of the PMF. From an analysis of LF(N)/EF(N)
      chimera proteins, we identified two 10-residue cassettes comprised of charged
      sequence that were responsible for the impaired translocation kinetics of EF(N).
      These cassettes have nonspecific electrostatic requirements: one surprisingly
      prefers acidic residues when driven by either a Deltapsi or a DeltapH; the second
      requires basic residues only when driven by a Deltapsi. Through modeling and
      experiment, we identified a charged surface in the PA channel responsible for
      charge selectivity. The charged surface latches the substrate and promotes PMF
      driven transport. We propose an electrostatic ratchet in the channel, comprised
      of opposing rings of charged residues, enforces directionality by interacting
      with charged cassettes in the substrate, thereby generating forces sufficient to
      drive unfolding.

PMID- 23115234
TI  - Mammalian target of rapamycin (mTOR) signaling network in skeletal myogenesis.
AB  - Mammalian (or mechanistic) target of rapamycin (mTOR) regulates a wide range of
      cellular and developmental processes by coordinating signaling responses to
      mitogens, nutrients, and various stresses. Over the last decade, mTOR has emerged
      as a master regulator of skeletal myogenesis, controlling multiple stages of the
      myofiber formation process. In this minireview, we present an emerging view of
      the signaling network underlying mTOR regulation of myogenesis, which contrasts
      with the well established mechanisms in the regulation of cell and muscle growth.
      Current questions for future studies are also highlighted.

PMID- 23115235
TI  - The RING finger protein RNF8 ubiquitinates Nbs1 to promote DNA double-strand
      break repair by homologous recombination.
AB  - Ubiquitination plays an important role in the DNA damage response. We identified
      a novel interaction of the E3 ubiquitin ligase RNF8 with Nbs1, a key regulator of
      DNA double-strand break (DSB) repair. We found that Nbs1 is ubiquitinated both
      before and after DNA damage and is a direct ubiquitination substrate of RNF8. We
      also identified key residues on Nbs1 that are ubiquitinated by RNF8. By using
      laser microirradiation and live-cell imaging, we observed that RNF8 and its
      ubiquitination activity are important for promoting optimal binding of Nbs1 to
      DSB-containing chromatin. We also demonstrated that RNF8-mediated ubiquitination
      of Nbs1 contributes to the efficient and stable binding of Nbs1 to DSBs and is
      important for HR-mediated DSB repair. Taken together, these studies suggest that
      Nbs1 is one important target of RNF8 to regulate DNA DSB repair.

PMID- 23115236
TI  - The heat shock response is modulated by and interferes with toxic effects of
      scrapie prion protein and amyloid beta.
AB  - The heat shock response (HSR) is an evolutionarily conserved pathway designed to
      maintain proteostasis and to ameliorate toxic effects of aberrant protein
      folding. We have studied the modulation of the HSR by the scrapie prion protein
      (PrP(Sc)) and amyloid beta peptide (Abeta) and investigated whether an activated
      HSR or the ectopic expression of individual chaperones can interfere with PrP(Sc)
      or Abeta-induced toxicity. First, we observed different effects on the HSR under
      acute or chronic exposure of cells to PrP(Sc) or Abeta. In chronically exposed
      cells the threshold to mount a stress response was significantly increased,
      evidenced by a decreased expression of Hsp72 after stress, whereas an acute
      exposure lowered the threshold for stress-induced expression of Hsp72. Next, we
      employed models of PrP(Sc)- and Abeta-induced toxicity to demonstrate that the
      induction of the HSR ameliorates the toxic effects of both PrP(Sc) and Abeta.
      Similarly, the ectopic expression of cytosolic Hsp72 or the extracellular
      chaperone clusterin protected against PrP(Sc)- or Abeta-induced toxicity.
      However, toxic signaling induced by a pathogenic PrP mutant located at the plasma
      membrane was prevented by an activated HSR or Hsp72 but not by clusterin,
      indicating a distinct mode of action of this extracellular chaperone. Our study
      supports the notion that different pathological protein conformers mediate toxic
      effects via similar cellular pathways and emphasizes the possibility to exploit
      the heat shock response therapeutically.

PMID- 23115237
TI  - The mRNA-stabilizing factor HuR protein is targeted by beta-TrCP protein for
      degradation in response to glycolysis inhibition.
AB  - The mRNA-stabilizing protein HuR acts a stress response protein whose function
      and/or protein stability are modulated by diverse stress stimuli through
      posttranslational modifications. Here, we report a novel mechanism by which
      metabolic stress facilitates proteasomal degradation of HuR in cancer cells. In
      response to the glucose transporter inhibitor CG-5, HuR translocates to the
      cytoplasm, where it is targeted by the ubiquitin E3 ligase beta-TrCP1 for
      degradation. The cytoplasmic localization of HuR is facilitated by PKCalpha
      mediated phosphorylation at Ser-318 as the Ser-318 -> alanine substitution
      abolishes the ability of the resulting HuR to bind PKCalpha and to undergo
      nuclear export. The mechanistic link between beta-TrCP1 and HuR degradation was
      supported by the ability of ectopically expressed beta-TrCP1 to mimic CG-5 to
      promote HuR degradation and by the protective effect of dominant negative
      inhibition of beta-TrCP1 on HuR ubiquitination and degradation. Substrate
      targeting of HuR by beta-TrCP1 was further verified by coimmunoprecipitation and
      in vitro GST pull-down assays and by the identification of a beta-TrCP1
      recognition site. Although HuR does not contain a DSG destruction motif, we
      obtained evidence that beta-TrCP1 recognizes an unconventional motif,
      (296)EEAMAIAS(304), in the RNA recognition motif 3. Furthermore, mutational
      analysis indicates that IKKalpha-dependent phosphorylation at Ser-304 is crucial
      to the binding of HuR to beta-TrCP1. Mechanistically, this HuR degradation
      pathway differs from that reported for heat shock and hypoxia, which underlies
      the complexity in the regulation of HuR turnover under different stress stimuli.
      The ability of glycolysis inhibitors to target the expression of oncogenic
      proteins through HuR degradation might foster novel strategies for cancer
      therapy.

PMID- 23115238
TI  - Revisiting the nucleotide and aminoglycoside substrate specificity of the
      bifunctional aminoglycoside acetyltransferase(6')-Ie/aminoglycoside
      phosphotransferase(2'')-Ia enzyme.
AB  - The bifunctional aminoglycoside-modifying enzyme aminoglycoside
      acetyltransferase(6')-Ie/aminoglycoside phosphotransferase(2")-Ia, or AAC(6')
      Ie/APH(2")-Ia, is the major source of aminoglycoside resistance in gram-positive
      bacterial pathogens. In previous studies, using ATP as the cosubstrate, it was
      reported that the APH(2")-Ia domain of this enzyme is unique among aminoglycoside
      phosphotransferases, having the ability to inactivate an unusually broad spectrum
      of aminoglycosides, including 4,6- and 4,5-disubstituted and atypical. We
      recently demonstrated that GTP, and not ATP, is the preferred cosubstrate of this
      enzyme. We now show, using competition assays between ATP and GTP, that GTP is
      the exclusive phosphate donor at intracellular nucleotide levels. In light of
      these findings, we reevaluated the substrate profile of the phosphotransferase
      domain of this clinically important enzyme. Steady-state kinetic characterization
      using the phosphate donor GTP demonstrates that AAC(6')-Ie/APH(2")-Ia
      phosphorylates 4,6-disubstituted aminoglycosides with high efficiency
      (k(cat)/K(m) = 10(5)-10(7) M(-1) s(-1)). Despite this proficiency, no resistance
      is conferred to some of these antibiotics by the enzyme in vivo. We now show that
      phosphorylation of 4,5-disubstituted and atypical aminoglycosides are negligible
      and thus these antibiotics are not substrates. Instead, these aminoglycosides
      tend to stimulate an intrinsic GTPase activity of the enzyme. Taken together, our
      data show that the bifunctional enzyme efficiently phosphorylates only 4,6
      disubstituted antibiotics; however, phosphorylation does not necessarily result
      in bacterial resistance. Hence, the APH(2")-Ia domain of the bifunctional AAC(6')
      Ie/APH(2")-Ia enzyme is a bona fide GTP-dependent kinase with a narrow substrate
      profile, including only 4,6-disubstituted aminoglycosides.

PMID- 23115239
TI  - Role of conformational dynamics in alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionic acid (AMPA) receptor partial agonism.
AB  - We have investigated the range of cleft closure conformational states that the
      agonist-binding domains of the alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionic acid (AMPA) receptors occupy when bound to a series of willardiine
      derivatives using single-molecule FRET. These studies show that the agonist
      binding domain exhibits varying degrees of dynamics when bound to the different
      willardiines with differing efficacies. The chlorowillardiine- and
      nitrowillardiine-bound form of the agonist-binding domain probes a narrower range
      of cleft closure states relative to the iodowillardiine bound form of the
      protein, with the antagonist (alphaS)-alpha-amino-3-[(4-carboxyphenyl)methyl]-3,4
      dihydro-2,4-dioxo-1(2H)-pyrimidinepropanoic acid (UBP-282)-bound form exhibiting
      the widest range of cleft closure states. Additionally, the average cleft closure
      follows the order UBP-282 > iodowillardiine > chlorowillardiine >
      nitrowillardiine-bound forms of agonist-binding domain. These single-molecule
      FRET data, along with our previously reported data for the glutamate-bound forms
      of wild type and T686S mutant proteins, show that the mean currents under
      nondesensitizing conditions can be directly correlated to the fraction of the
      agonist-binding domains in the "closed" cleft conformation. These results
      indicate that channel opening in the AMPA receptors is controlled by both the
      ability of the agonist to induce cleft closure and the dynamics of the agonist
      binding domain when bound to the agonist.

PMID- 23115240
TI  - Functional analysis of missense mutations in Kv8.2 causing cone dystrophy with
      supernormal rod electroretinogram.
AB  - Mutations in KCNV2 have been proposed as the molecular basis for cone dystrophy
      with supernormal rod electroretinogram. KCNV2 codes for the modulatory voltage
      gated potassium channel alpha-subunit, Kv8.2, which is incapable of forming
      functional channels on its own. Functional heteromeric channels are however
      formed with Kv2.1 in heterologous expression systems, with both alpha-subunit
      genes expressed in rod and cone photoreceptors. Of the 30 mutations identified in
      the KCNV2 gene, we have selected three missense mutations localized in the
      potassium channel pore and two missense mutations localized in the
      tetramerization domain for analysis. We characterized the differences between
      homomeric Kv2.1 and heteromeric Kv2.1/Kv8.2 channels and investigated the
      influence of the selected mutations on the function of heteromeric channels. We
      found that two pore mutations (W467G and G478R) led to the formation of
      nonconducting heteromeric Kv2.1/Kv8.2 channels, whereas the mutations localized
      in the tetramerization domain prevented heteromer generation and resulted in the
      formation of homomeric Kv2.1 channels only. Consequently, our study suggests the
      existence of two distinct molecular mechanisms involved in the disease pathology.

PMID- 23115241
TI  - Activation of phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein
      kinase (MAPK) signaling and the consequent induction of transformation by
      overexpressed 14-3-3gamma protein require specific amino acids within 14-3-3gamma
      N-terminal variable region II.
AB  - Members of the 14-3-3 superfamily regulate numerous cellular functions by binding
      phosphoproteins. The seven human isoforms (and the myriad of other eukaryotic 14
      3-3 proteins) are highly conserved in amino acid sequence and secondary
      structure, yet there is abundant evidence that the various isoforms manifest
      disparate as well as common functions. Several of the human 14-3-3 isoforms are
      dysregulated in certain cancers and thus have been implicated in oncogenesis;
      experimentally, 14-3-3gamma behaves as an oncogene, whereas 14-3-3sigma acts as a
      tumor suppressor. In this study, we sought to localize these opposing phenotypes
      to specific regions of the two isoforms and then to individual amino acids
      therein. Using a bioinformatics approach, six variable regions (VRI-VRVI) were
      identified. Using this information, two sets of constructs were created in which
      N-terminal portions (including either VRI-IV or only VRI and VRII) of 14-3-3gamma
      and 14-3-3sigma were swapped; NIH3T3 cells overexpressing the four chimeric
      proteins were tested for transformation activity (focus formation, growth in soft
      agar) and activation of PI3K and MAPK signaling. We found that the specific
      phenotypes of 14-3-3gamma are associated with the N-terminal 40 amino acids (VRI
      and VRII); in like fashion, VRI and VRII of 14-3-3sigma dictated its tumor
      suppressor function. Using individual amino acid substitutions within the 14-3
      3gamma VRII, we identified two residues required for and two contributing to the
      gamma-specific phenotypes. Our observations suggest that isoform-specific
      phenotypes are dictated by a relatively few amino acids within variable regions.

PMID- 23115242
TI  - Identification of an N-terminal truncation of the NF-kappaB p65 subunit that
      specifically modulates ribosomal protein S3-dependent NF-kappaB gene expression.
AB  - NF-kappaB is a pleiotrophic transcription factor that plays a prominent
      regulatory role in various cellular processes. Although previous efforts have
      focused on its activation, how NF-kappaB selects specific target genes in
      response to discrete signals remains puzzling. In addition to the well defined
      Rel protein components of NF-kappaB, the ribosomal protein S3 (RPS3) was
      identified to be an essential component of specific NF-kappaB complexes. RPS3
      synergistically interacts with the NF-kappaB p65 subunit to achieve optimal
      binding and transactivation of a subset of NF-kappaB target genes, thus providing
      regulatory specificity. Emerging evidence suggests an important role for the RPS3
      p65 interaction in context-specific NF-kappaB gene transcription. The food-borne
      pathogen Escherichia coli O157:H7 impacts the transcription of a subset of NF
      kappaB target genes encoding proinflammatory cytokines and chemokines in host
      cells by preventing the nuclear translocation of RPS3, but not p65. The N
      terminus of p65 is crucial for RPS3 binding. Although several p65 N-terminal
      fragments are generated by either protease cleavage or alternative mRNA splicing
      under certain pathophysiological conditions, the role of these fragments in
      modulating NF-kappaB signaling, in particular RPS3-dependent selective gene
      transcription, has not been fully characterized. Here we report that an N
      terminal fragment of p65 (amino acids 21-186) can selectively modulate NF-kappaB
      gene transcription by competing for RPS3 binding to p65. This 21-186 fragment
      preferentially localizes in the cytoplasm where it delays stimuli-induced RPS3
      nuclear translocation, without affecting the nuclear translocation of p65. Our
      findings thus uncover a new cytoplasmic function for the N-terminal domain of p65
      and provide a novel strategy for selective inhibition of NF-kappaB gene
      transcription.

PMID- 23115243
TI  - Induction of DNA demethylation depending on two sets of Sox2 and adjacent Oct3/4
      binding sites (Sox-Oct motifs) within the mouse H19/insulin-like growth factor 2
      (Igf2) imprinted control region.
AB  - DNA demethylation is used to establish and maintain an unmethylated state. The
      molecular mechanisms to induce DNA demethylation at a particular genomic locus
      remain unclear. The mouse H19/insulin-like growth factor 2 (Igf2) imprinted
      control region (ICR) is a methylation state-sensitive insulator that regulates
      transcriptional activation of both genes. The unmethylated state of the ICR
      established in female germ cells is maintained during development, resisting the
      wave of genome-wide de novo methylation. We previously demonstrated that a DNA
      fragment (fragment b) derived from this ICR-induced DNA demethylation when it was
      transfected into undifferentiated mouse embryonal carcinoma cell lines. Moreover,
      two octamer motifs within fragment b were necessary to induce this DNA
      demethylation. Here, we demonstrated that both octamer motifs and their flanking
      sequences constitute Sox-Oct motifs (SO1 and SO2) and that the SO1 region, which
      requires at least four additional elements, including the SO2 region, contributes
      significantly to the induction of high-frequency DNA demethylation as a Sox-Oct
      motif. Moreover, RNAi-mediated inhibition of Oct3/4 expression in P19 cells
      resulted in a reduced DNA demethylation frequency of fragment b but not of the
      adenine phosphoribosyltransferase gene CpG island. The Sox motif of SO1 could
      function as a sensor for a hypermethylated state of the ICR to repress
      demethylation activity. These results indicate that Sox-Oct motifs in the ICR
      determine the cell type, DNA region, and allele specificity of DNA demethylation.
      We propose a link between the mechanisms for maintenance of the unmethylated
      state of the H19/Igf2 ICR and the undifferentiated cell-specific induction of DNA
      demethylation.

PMID- 23115244
TI  - Cells lacking pfh1, a fission yeast homolog of mammalian frataxin protein,
      display constitutive activation of the iron starvation response.
AB  - Friedreich ataxia is a genetic disease caused by deficiencies in frataxin. This
      protein has homologs not only in higher eukaryotes but also in bacteria, fungi,
      and plants. The function of this protein is still controversial. We have
      identified a frataxin homolog in fission yeast, and we have analyzed whether its
      depletion leads to any of the phenotypes observed in other organisms. Cells
      deleted in pfh1 are sensitive to growth under aerobic conditions, display
      increased levels of total iron, hallmarks of oxidative stress such as protein
      carbonylation, decreased aconitase activity, and lower levels of oxygen
      consumption compared with wild-type cells. This mitochondrial protein seems to be
      important for iron and/or reactive oxygen species homeostasis. We have analyzed
      the proteome of cells devoid of Pfh1, and we determined that gene products up-
      and down-regulated upon iron depletion in wild-type cells are constitutively
      misregulated in this mutant. Because of the particular signaling pathway
      components governing the iron starvation response in fission yeast, our
      experiments suggest that cells lacking Pfh1 display a decrease of cytosolic
      available iron that triggers activation of Grx4, the common regulator of the iron
      starvation gene expression program. Our Schizosaccharomyces pombe Deltapfh1
      strain constitutes a new and useful model system to study Friedreich ataxia.

PMID- 23115245
TI  - A small novel A-kinase anchoring protein (AKAP) that localizes specifically
      protein kinase A-regulatory subunit I (PKA-RI) to the plasma membrane.
AB  - Protein kinase A-anchoring proteins (AKAPs) provide spatio-temporal specificity
      for the omnipotent cAMP-dependent protein kinase (PKA) via high affinity
      interactions with PKA regulatory subunits (PKA-RI, RII). Many PKA-RII-AKAP
      complexes are heavily tethered to cellular substructures, whereas PKA-RI-AKAP
      complexes have remained largely undiscovered. Here, using a cAMP affinity-based
      chemical proteomics strategy in human heart and platelets, we uncovered a novel,
      ubiquitously expressed AKAP, termed small membrane (sm)AKAP due to its specific
      localization at the plasma membrane via potential myristoylation/palmitoylation
      anchors. In vitro binding studies revealed specificity of smAKAP for PKA-RI (K(d)
      = 7 nM) over PKA-RII (K(d) = 53 nM) subunits, co-expression of smAKAP with the
      four PKA R subunits revealed an even more exclusive specificity of smAKAP for PKA
      RIalpha/beta in the cellular context. Applying the singlet oxygen-generating
      electron microscopy probe miniSOG indicated that smAKAP is tethered to the plasma
      membrane and is particularly dense at cell-cell junctions and within filopodia.
      Our preliminary functional characterization of smAKAP provides evidence that,
      like PKA-RII, PKA-RI can be tightly tethered by a novel repertoire of AKAPs,
      providing a new perspective on spatio-temporal control of cAMP signaling.

PMID- 23115246
TI  - MUNC13-4 protein regulates the oxidative response and is essential for phagosomal
      maturation and bacterial killing in neutrophils.
AB  - Neutrophils use diverse mechanisms to kill pathogens including phagocytosis,
      exocytosis, generation of reactive oxygen species (ROS), and neutrophil
      extracellular traps. These mechanisms rely on their ability to mobilize
      intracellular organelles and to deliver granular cargoes to specific cellular
      compartments or into the extracellular milieu, but the molecular mechanisms
      regulating vesicular trafficking in neutrophils are not well understood. MUNC13-4
      is a RAB27A effector that coordinates exocytosis in hematopoietic cells, and its
      deficiency is associated with the human immunodeficiency familial hemophagocytic
      lymphohistiocytosis type 3. In this work, we have established an essential role
      for MUNC13-4 in selective vesicular trafficking, phagosomal maturation, and
      intracellular bacterial killing in neutrophils. Using neutrophils from munc13-4
      knock-out (KO) mice, we show that MUNC13-4 is necessary for the regulation of
      p22(phox)-expressing granule trafficking to the plasma membrane and regulates
      extracellular ROS production. MUNC13-4 was also essential for the regulation of
      intracellular ROS production induced by Pseudomonas aeruginosa despite normal
      trafficking of p22(phox)-expressing vesicles toward the phagosome. Importantly,
      in the absence of MUNC13-4, phagosomal maturation was impaired as observed by the
      defective delivery of azurophilic granules and multivesicular bodies to the
      phagosome. Significantly, this mechanism was intact in RAB27A KO neutrophils.
      Intracellular bacterial killing was markedly impaired in MUNC13-4 KO neutrophils.
      MUNC13-4-deficient cells showed a significant increase in neutrophil
      extracellular trap formation but were unable to compensate for the impaired
      bacterial killing. Altogether, these findings characterize novel functions of
      MUNC13-4 in the innate immune response of the neutrophil and have direct
      implications for the understanding of immunodeficiencies in patients with MUNC13
      4 deficiency.

PMID- 23115247
TI  - Functional glycomic analysis of human milk glycans reveals the presence of virus
      receptors and embryonic stem cell biomarkers.
AB  - Human milk contains a large diversity of free glycans beyond lactose, but their
      functions are not well understood. To explore their functional recognition, here
      we describe a shotgun glycan microarray prepared from isolated human milk glycans
      (HMGs), and our studies on their recognition by viruses, antibodies, and glycan
      binding proteins (GBPs), including lectins. The total neutral and sialylated HMGs
      were derivatized with a bifunctional fluorescent tag, separated by
      multidimensional HPLC, and archived in a tagged glycan library, which was then
      used to print a shotgun glycan microarray (SGM). This SGM was first interrogated
      with well defined GBPs and antibodies. These data demonstrated both the utility
      of the array and provided preliminary structural information (metadata) about
      this complex glycome. Anti-TRA-1 antibodies that recognize human pluripotent stem
      cells specifically recognized several HMGs that were then further structurally
      defined as novel epitopes for these antibodies. Human influenza viruses and
      Parvovirus Minute Viruses of Mice also specifically recognized several HMGs. For
      glycan sequencing, we used a novel approach termed metadata-assisted glycan
      sequencing (MAGS), in which we combine information from analyses of glycans by
      mass spectrometry with glycan interactions with defined GBPs and antibodies
      before and after exoglycosidase treatments on the microarray. Together, these
      results provide novel insights into diverse recognition functions of HMGs and
      show the utility of the SGM approach and MAGS as resources for defining novel
      glycan recognition by GBPs, antibodies, and pathogens.

PMID- 23115248
TI  - Arabidopsis microtubule destabilizing protein40 is involved in brassinosteroid
      regulation of hypocotyl elongation.
AB  - The brassinosteroid (BR) phytohormones play crucial roles in regulating plant
      cell growth and morphogenesis, particularly in hypocotyl cell elongation. The
      microtubule cytoskeleton is also known to participate in the regulation of
      hypocotyl elongation. However, it is unclear if BR regulation of hypocotyl
      elongation involves the microtubule cytoskeleton. In this study, we demonstrate
      that BRs mediate hypocotyl cell elongation by influencing the orientation and
      stability of cortical microtubules. Further analysis identified the previously
      undiscovered Arabidopsis thaliana microtubule destabilizing protein40 (MDP40) as
      a positive regulator of hypocotyl cell elongation. Brassinazole-resistant1, a key
      transcription factor in the BR signaling pathway, directly targets and
      upregulates MDP40. Overexpression of MDP40 partially rescued the shorter
      hypocotyl phenotype in BR-deficient mutant de-etiolated-2 seedlings.
      Reorientation of the cortical microtubules in the cells of MDP40 RNA interference
      transgenic lines was less sensitive to BR. These findings demonstrate that MDP40
      is a key regulator in BR regulation of cortical microtubule reorientation and
      mediates hypocotyl growth. This study reveals a mechanism involving BR regulation
      of microtubules through MDP40 to mediate hypocotyl cell elongation.

PMID- 23115249
TI  - Constitutively active mitogen-activated protein kinase versions reveal functions
      of Arabidopsis MPK4 in pathogen defense signaling.
AB  - Plant mitogen-activated protein kinases (MAPKs) are involved in important
      processes, including stress signaling and development. In a functional yeast
      screen, we identified mutations that render Arabidopsis thaliana MAPKs
      constitutively active (CA). Importantly, CA-MAPKs maintain their specificity
      toward known activators and substrates. As a proof-of-concept, Arabidopsis MAPK4
      (MPK4) function in plant immunity was investigated. In agreement with the
      phenotype of mpk4 mutants, CA-MPK4 plants were compromised in pathogen-induced
      salicylic acid accumulation and disease resistance. MPK4 activity was found to
      negatively regulate pathogen-associated molecular pattern-induced reactive oxygen
      species production but had no impact on callose deposition, indicating that CA
      MPK4 allows discriminating between processes regulated by MPK4 activity from
      processes indirectly affected by mpk4 mutation. Finally, MPK4 activity was also
      found to compromise effector-triggered immunity conditioned by the Toll
      Interleukin-1 Receptor-nucleotide binding (NB)-Leu-rich repeat (LRR) receptors
      RPS4 and RPP4 but not by the coiled coil-NB-LRR receptors RPM1 and RPS2. Overall,
      these data reveal important insights on how MPK4 regulates plant defenses and
      establishes that CA-MAPKs offer a powerful tool to analyze the function of plant
      MAPK pathways.

PMID- 23115251
TI  - Return or retirement?

PMID- 23115250
TI  - The role of plants in the effects of global change on nutrient availability and
      stoichiometry in the plant-soil system.

PMID- 23115253
TI  - The feasibility of randomized controlled trials for early arthritis therapies
      (Earth) involving acute anterior cruciate ligament tear cohorts.
AB  - Osteoarthritis (OA) is a leading cause of disability for which disease-modifying
      treatments are lacking. Anterior cruciate ligament (ACL) tear provides
      opportunities to study potential interventions from the initiation of heightened
      OA risk at the time of injury. This institutional review board (IRB)-approved
      prospective cross-sectional study (level of evidence: 2) was performed to test
      the hypothesis that adequate sample sizes of ACL-injured subjects to support
      randomized controlled trials (RCT) of early intervention strategies can be
      achieved. A total of 307 ACL-injured patients were entered into the database from
      3-month collection periods at 7 clinical sites, with 65 subjects aged 18 to 30
      years passing the inclusion/exclusion criteria. From sites that were IRB approved
      to ask, 89 of 96 (93%) subjects were willing to participate in an RCT.
      Extrapolating the 3-month data to a 1-year recruitment period would potentially
      yield 242 subjects aged 18 to 30 years willing to undergo randomization. This
      study shows that adequate sample sizes to perform RCT of early intervention
      strategies in ACL-injured cohorts comprising healthy young adults ages 18 to and
      30 without prior joint injuries can be achieved within 1 to 2 years through
      recruitment at 5 to 7 orthopaedic sports medicine practices. Continued
      development of ACL-tear cohorts will provide the clinical base to critically
      evaluate new diagnostic and therapeutic strategies that can help transform
      clinical care of OA from palliation to prevention.

PMID- 23115254
TI  - Safety of modern starches used during surgery.
AB  - Various hydroxyethyl starch (HES) preparations have been used for decades to
      augment blood volume. There has been concern recently regarding possible adverse
      outcomes when using HES in the intensive care setting, especially in patients
      with septic shock. However, the pharmacokinetic and pharmacodynamic properties of
      HES preparations depend on their chemical composition and source material. Thus,
      different clinical conditions could result in differing effectiveness and safety
      for these preparations. Consequently, we assessed the safety of tetrastarches
      when used during surgery, using a formal search, that yielded 59 primary full
      publications of studies that met a priori inclusion criteria and randomly
      allocated 4529 patients with 2139 patients treated with tetrastarch compared with
      2390 patients treated with a comparator. There were no indications that the use
      of tetrastarches during surgery induces adverse renal effects as assessed by
      change or absolute concentrations of serum creatinine or need for renal
      replacement therapy (39 trials, 3389 patients), increased blood loss (38 trials,
      3280 patients), allogeneic erythrocyte transfusion (20 trials, 2151 patients;
      odds ratio for HES transfusion 0.73 [95% confidence interval = 0.61-0.87], P =
      0.0005), or increased mortality (odds ratio for HES mortality = 0.51 [0.24-1.05],
      P = 0.079).

PMID- 23115255
TI  - Incidence, predictors, and outcomes of perioperative stroke in noncarotid major
      vascular surgery.
AB  - BACKGROUND: Perioperative stroke is a potentially catastrophic complication of
      surgery. Patients undergoing vascular surgery suffer from systemic
      atherosclerosis and are expected to be at increased risk for this complication.
      We studied the incidence, predictors, and outcomes of perioperative stroke after
      noncarotid major vascular surgery using the American College of Surgeons National
      Quality Improvement Program database. METHODS: Forty-seven thousand seven hundred
      fifty patients undergoing noncarotid vascular surgery from 2005 to 2009 at
      nonVeterans Administration hospitals were identified from the American College of
      Surgeons National Quality Improvement Program database. An analysis of patients
      undergoing elective lower extremity amputation, lower extremity
      revascularization, or open aortic procedures was performed to determine the
      incidence, independent predictors, and 30-day mortality of perioperative stroke.
      RESULTS: The overall incidence of perioperative stroke within 30 days of surgery
      (n=37,927) was 0.6%. Multivariate analysis revealed that each 1-year increase in
      age [odds ratio 1.02, 95% confidence interval (CI) (1.01 to 1.04)], cardiac
      history [1.42, (1.07 to 1.87)], female sex [1.47, (1.12 to 1.93)], history of
      cerebrovascular disease [1.72, (1.29 to 2.29)], and acute renal failure or
      dialysis dependence [2.03, (1.39 to 2.97)] were independent predictors of stroke.
      Only 15% (95% CI, 11%-20%) of strokes occurred on postoperative day 0 or 1.
      Perioperative stroke was associated with a 3-fold increase in 30-day all-cause
      mortality [3.36, (1.77 to 6.36)] and an increased median surgical length of stay
      from 6 (95% CI, 2 to 28) to 13 (95% CI, 3 to 43) days (P<0.001, WMWodds 2.5, 95%
      CI, 2.0 to 3.2) in a matched-cohort assessment. CONCLUSION: Perioperative stroke
      is an important source of morbidity and mortality, as reflected by significant
      increases in median surgical length of stay and all-cause 30-day mortality. The
      independent predictors of stroke that we have identified in this population are
      not readily modifiable and the majority of strokes occurred after postoperative
      day 1. Additional studies are required to identify potentially modifiable
      intraoperative or postoperative risk factors of perioperative stroke.

PMID- 23115256
TI  - Repolarization abnormalities in patients with subarachnoid and intracerebral
      hemorrhage: predisposing factors and association with outcome.
AB  - BACKGROUND: Electrocardiographic (ECG) abnormalities are frequent in patients
      with intracranial insult. In this study, we evaluated the factors predisposing to
      the repolarization abnormalities, i.e., prolonged corrected QT (QTc) interval,
      ischemic-like ECG changes and morphologic end-repolarization abnormalities, and
      examined the prognostic value of these abnormalities in patients with
      subarachnoid and intracerebral hemorrhages requiring intensive care. METHODS:
      This was a prospective, observational clinical study in a university-level
      intensive care unit. Clinical characteristics, the level of consciousness, and
      findings in primary head computed tomography were recorded on admission. The
      study period was divided into three 2-day sections. In each section, a 12-lead
      ECG, transthoracic echocardiography, the results of standard blood electrolytes
      and cardiac troponin I, as well as the rate of vasoactive and sedative drug
      infusions were recorded. Repolarization abnormalities such as prolongation of the
      QTc interval (millisecond), ischemic-like ECG changes, and morphologic end
      repolarization abnormalities (present/absent) were evaluated and analyzed. The 1
      year functional outcome was determined using the Glasgow Outcome Score. RESULTS:
      During the 2-year study period, 108 patients were included in the study.
      Different repolarization abnormalities were frequent in both types of hemorrhage.
      Prolongation of the QTc interval was predisposed by female gender (beta, 24.5; P
      = 0.010) and the use of propofol (beta, 30.5; P = 0.001). The predisposing factor
      for ischemic-like ECG changes were male gender (odds ratio [OR], 5.9; P = 0.003)
      and for morphological end-repolarization abnormalities aneurysmatic bleeding (OR,
      13.0; P = 0.002). Ischemic-like ECG changes were common, in 87/108 patients
      during the study period, and were associated with a poorer 1-year functional
      outcome (OR, 4.7; lower 95% confidence interval, 1.5; P = 0.010). CONCLUSIONS:
      Each repolarization abnormality has characteristic predisposing factors. Ischemic
      like ECG changes are common and are associated with a poorer 1-year functional
      outcome.

PMID- 23115257
TI  - Comparison of sequencing (barcode region) and sequence-tagged-site PCR for
      Blastocystis subtyping.
AB  - Blastocystis is the most common nonfungal microeukaryote of the human intestinal
      tract and comprises numerous subtypes (STs), nine of which have been found in
      humans (ST1 to ST9). While efforts continue to explore the relationship between
      human health status and subtypes, no consensus regarding subtyping methodology
      exists. It has been speculated that differences detected in subtype distribution
      in various cohorts may to some extent reflect different approaches. Blastocystis
      subtypes have been determined primarily in one of two ways: (i) sequencing of
      small subunit rRNA gene (SSU-rDNA) PCR products and (ii) PCR with subtype
      specific sequence-tagged-site (STS) diagnostic primers. Here, STS primers were
      evaluated against a panel of samples (n = 58) already subtyped by SSU-rDNA
      sequencing (barcode region), including subtypes for which STS primers are not
      available, and a small panel of DNAs from four other eukaryotes often present in
      feces (n = 18). Although the STS primers appeared to be highly specific, their
      sensitivity was only moderate, and the results indicated that some infections may
      go undetected when this method is used. False-negative STS results were not
      linked exclusively to certain subtypes or alleles, and evidence of substantial
      genetic variation in STS loci was obtained. Since the majority of DNAs included
      here were extracted from feces, it is possible that STS primers may generally
      work better with DNAs extracted from Blastocystis cultures. In conclusion, due to
      its higher applicability and sensitivity, and since sequence information is
      useful for other forms of research, SSU-rDNA barcoding is recommended as the
      method of choice for Blastocystis subtyping.

PMID- 23115258
TI  - Analysis of mutations in the S gene of hepatitis B virus strains in patients with
      chronic infection by online bioinformatics tools.
AB  - Hepatitis B virus (HBV) genomes show a high rate of mutations. This can lead to a
      variety of amino acid changes in the surface and polymerase genes, causing
      changes in viral protein conformation that can result in diminished antibody
      binding or decreased secretion of surface antigen (HBsAg). HBV monitoring
      increasingly relies on HBsAg detection and quantification, and therefore
      epidemiological data on HBsAg mutations are needed. We therefore analyzed the
      frequency of HBsAg mutations possibly influencing the quantification of HBsAg
      (MUPIQHs) in an unselected patient collective. To this end, we determined the HBV
      surface and polymerase gene sequences of an unselected patient collective of 237
      individuals chronically infected with HBV and analyzed the MUPIQHs in these
      sequences using three different online HBV sequence analysis tools. We found that
      17 or 34% of the patients, depending on the online interpretation algorithm used,
      harbored MUPIQHs and that MUPIQHs were not significantly associated with the
      duration of disease, treatment, or HBV genotype. Thus, this study shows that a
      substantial amount of HBV sequences derived from unselected patients chronically
      infected with HBV carry MUPIQHs, and therefore the reliability of routine
      quantitative and qualitative HBsAg tests needs to be reevaluated.

PMID- 23115259
TI  - Global phylogeny of Shigella sonnei strains from limited single nucleotide
      polymorphisms (SNPs) and development of a rapid and cost-effective SNP-typing
      scheme for strain identification by high-resolution melting analysis.
AB  - The current Shigella sonnei pandemic involves geographically associated,
      multidrug-resistant clones. This study has demonstrated that S. sonnei phylogeny
      can be accurately defined with limited single nucleotide polymorphisms (SNPs). By
      typing 6 informative SNPs using a high-resolution melting (HRM) assay, major S.
      sonnei lineages/sublineages can be identified as defined by whole-genome
      variation.

PMID- 23115260
TI  - Environmental contamination by carbapenem-resistant Enterobacteriaceae.
AB  - In the last decade, the global emergence of carbapenem resistance in
      Enterobacteriaceae has posed great concern to public health. Data concerning the
      role of environmental contamination in the dissemination of carbapenem-resistant
      Enterobacteriaceae (CRE) are currently lacking. Here, we aimed to examine the
      extent of CRE contamination in various sites in the immediate surroundings of CRE
      carriers and to assess the effects of sampling time and cleaning regimens on the
      recovery rate. We evaluated the performance of two sampling methods, CHROMAgar
      KPC contact plate and eSwab, for the detection of environmental CRE. eSwab was
      followed either by direct plating or by broth enrichment. First, 14 sites in the
      close vicinity of the carrier were evaluated for environmental contamination, and
      5, which were found to be contaminated, were further studied. The environmental
      contamination decreased with distance from the patient; the bed area was the most
      contaminated site. Additionally, we found that the sampling time and the cleaning
      regimen were critical factors affecting the prevalence of environmental CRE
      contamination. We found that the CHROMAgar KPC contact plate method was a more
      effective technique for detecting environmental CRE than were eSwab-based
      methods. In summary, our study demonstrated that the vicinity of patients
      colonized with CRE is often contaminated by these organisms. Using selective
      contact plates to detect environmental contamination may guide cleaning efficacy
      and assist with outbreak investigation in an effort to limit the spread of CRE.

PMID- 23115261
TI  - Acute right-sided heart failure caused by Neisseria meningitidis.
AB  - Meningococcal myocarditis is a rarely diagnosed infection and could be the
      consequence of primary invasive infection or late immunologic complications. An
      unusual presentation of meningococcemia in an immunocompetent adult is described,
      with Neisseria meningitidis identified as the cause of selective right-sided
      heart failure in a case of acute myocarditis.

PMID- 23115262
TI  - Close geographic association of human neoehrlichiosis and tick populations
      carrying "Candidatus Neoehrlichia mikurensis" in eastern Switzerland.
AB  - Neoehrlichiosis caused by "Candidatus Neoehrlichia mikurensis" is an emerging
      zoonotic disease. In total, six patients have been described in Europe, with the
      first case detected in 2007. In addition, seven patients from China were
      described in a report published in October 2012. In 2009, we diagnosed the first
      human case of "Ca. Neoehrlichia mikurensis" infection in the Zurich area
      (Switzerland). Here, we report two additional human cases from the same region,
      which were identified by broad-range 16S rRNA gene PCR. Both patients were
      immunocompromised and presented with similar clinical syndromes, including fever,
      malaise, and weight loss. A diagnostic multiplex real-time PCR was developed for
      specific detection of "Ca. Neoehrlichia mikurensis" infections. The assay is
      based on the signature sequence of a 280-bp fragment of the "Ca. Neoehrlichia
      mikurensis" 16S rRNA gene and incorporates a "Ca. Neoehrlichia mikurensis"
      species, a "Ca. Neoehrlichia" genus, and an Anaplasmataceae family probe for
      simultaneous screening. The analytical sensitivity was determined to be below
      five copies of the "Ca. Neoehrlichia mikurensis" 16S rRNA gene. Our results show
      that the assay is suitable for the direct detection of "Ca. Neoehrlichia
      mikurensis" DNA in clinical samples from, for example, blood and bone marrow. In
      addition, it allows for monitoring treatment response during antibiotic therapy.
      Using the same assay, DNA extracts from 1,916 ticks collected in four forests in
      close proximity to the patients' residences (<3 km) were screened. At all
      sampling sites, the minimal prevalence of "Ca. Neoehrlichia mikurensis" was
      between 3.5 to 8% in pools of either nymphs, males, or females, showing a strong
      geographic association between the three patients and the assumed vector.

PMID- 23115263
TI  - Using major outer membrane protein typing as an epidemiological tool to
      investigate outbreaks caused by milk-borne Campylobacter jejuni isolates in
      California.
AB  - We describe using major outer membrane protein (MOMP) typing as a screen to
      compare the Campylobacter jejuni porA gene sequences of clinical outbreak strains
      from human stool with the porA sequences of dairy farm strains isolated during
      two milk-borne campylobacteriosis outbreak investigations in California. The
      genetic relatedness of clinical and environmental strains with identical or
      closely related porA sequences was confirmed by multilocus sequence typing and
      pulsed-field gel electrophoresis analysis. The first outbreak involved 1,644 C.
      jejuni infections at 11 state correctional facilities and was associated with
      consumption of pasteurized milk supplied by an on-site dairy (dairy A) at a
      prison in the central valley. The second outbreak involved eight confirmed and
      three suspect C. jejuni cases linked to consumption of commercial raw milk and
      raw chocolate colostrum at another central valley dairy (dairy B). Both dairies
      bottled fluid milk on the farm and distributed the finished product to off-site
      locations. Altogether, C. jejuni was isolated from 7 of 15 (46.7%) bovine fecal,
      12 of 20 (60%) flush alley water, and 1 of 20 (5%) lagoon samples collected on
      dairy A. At dairy B, C. jejuni was cultured from 9 of 26 (34.6%) bovine fecal
      samples. Environmental strains indistinguishable from the clinical outbreak
      strains were found in five flush alley water samples (dairy A) and four bovine
      fecal samples (dairy B). The findings demonstrate that MOMP typing is a useful
      tool to triage environmental isolates prior to conducting more labor-intensive
      molecular typing methods.

PMID- 23115264
TI  - Identification by full-genome analysis of a bovine rotavirus transmitted directly
      to and causing diarrhea in a human child.
AB  - The genome of rotaviruses consists of 11 segments of double-stranded RNA, and
      each genome segment has multiple genotypes. Thus, the genotype constellation of
      an isolate is often indicative of its host species. Albeit rarely, interspecies
      transmission occurs either by virions with nonreassorted or reassorted genomic
      segments. A rotavirus with the G6P[1] genotype, Ro8059, was isolated from the
      stool of a 1-year-old child during routine characterization of diarrheal
      specimens from a sentinel clinic in Israel in 1995. Since genotype G6P[1] is
      generally associated with bovine rotaviruses, and the child developed diarrhea
      within days of his first contact with calves at an urban farm, the aim of this
      study was to characterize the whole genomic constellation of Ro8059 and four
      G6P[1] bovine strains, BRV101, BRV105, BRV106, and CR231/39, by RNA-RNA
      hybridization and full genome sequencing to determine whether some or all of the
      segments were of bovine origin. The genome constellations of all four bovine
      G6P[1] strains were G6-P[1]-I2-R2-C2-M2-A3-N2-T6-E2-H3 for VP7-VP4-VP6-VP1-VP2
      VP3-NSP1-NSP2-NSP3-NSP4-NSP5, respectively. Ro8059 shared the same genotype
      constellation with these bovine strains, with high nucleotide sequence identities
      (95.84 to 100%) for each of the 11 segments indicating that Ro8059 represented a
      direct interspecies whole-genome transmission of a nonreassorted rotavirus from a
      calf to a human infant. We conclude that this was the earliest example with a
      complete epidemiological link in which an entirely bovine rotavirus directly
      infected a human child and caused a symptomatic diarrheal illness. Thus, not all
      bovine rotaviruses are always naturally attenuated to the human host.

PMID- 23115265
TI  - Multilocus sequence typing for characterization of Staphylococcus
      pseudintermedius.
AB  - Staphylococcus pseudintermedius is an opportunistic pathogen in dogs. Four
      housekeeping genes with allelic polymorphisms were identified and used to develop
      an expanded multilocus sequence typing (MLST) scheme. The new seven-locus
      technique shows S. pseudintermedius to have greater genetic diversity than
      previous methods and discriminates more isolates based upon host origin.

PMID- 23115266
TI  - Population dynamics of tuberculous Bacilli in Cameroon as assessed by
      spoligotyping.
AB  - Genetic assessment by spoligotyping of 565 Mycobacterium tuberculosis complex
      strains collected from the Western Region of Cameroon between 2004 and 2005 has
      confirmed the establishment of the "Cameroon family" as the leading cause of
      tuberculosis in 45.9% of cases and evidenced the rapid quasi extinction of
      Mycobacterium africanum, isolated in 3.3% of tuberculosis cases.

PMID- 23115267
TI  - Porcine sperm bind to specific 6-sialylated biantennary glycans to form the
      oviduct reservoir.
AB  - After mating, many female mammals store a subpopulation of sperm in the lower
      portion of the oviduct, forming a reservoir. The reservoir lengthens sperm
      lifespan, regulates sperm capacitation, controls polyspermy, and selects normal
      sperm. It is believed that sperm bind to glycans on the oviduct epithelium to
      form the reservoir, but the specific adhesion molecules that retain sperm are
      unclear. Herein, using a glycan array to test 377 glycans for their ability to
      bind porcine sperm, we found two glycan motifs in common among all glycans with
      sperm-binding ability: the Lewis X trisaccharide and biantennary structures
      containing a mannose core with 6-sialylated lactosamine at one or more termini.
      Binding to both motifs was specific; isomers of each motif did not bind sperm.
      Further work focused on sialylated lactosamine. Sialylated lactosamine was found
      abundantly on the apical side of epithelial cells collected from the oviduct
      isthmus, among N-linked and O-linked glycans. Sialylated lactosamine bound to the
      head of sperm, the region that interacts with the oviduct epithelium. After
      capacitation, sperm lost affinity for sialylated lactosamine. Receptor
      modification may contribute to release from the reservoir so that sperm can move
      to the site of fertilization. Sialylated lactosamine was required for sperm to
      bind oviduct cells. Simbucus nigra agglutinin or an antibody specific to
      sialylated lactosamine with a preference for Neu5Acalpha2-6Gal rather than
      Neu5Acalpha2-3Gal reduced sperm binding to oviduct isthmic cells, as did
      occupying putative receptors on sperm with sialylated biantennary glycans. These
      results demonstrate that sperm binding to oviduct 6-sialylated biantennary
      glycans is necessary for normal adhesion to the oviduct.

PMID- 23115268
TI  - A systematic analysis of a deep mouse epididymal sperm proteome.
AB  - Spermatozoa are highly specialized cells that, when mature, are capable of
      navigating the female reproductive tract and fertilizing an oocyte. The sperm
      cell is thought to be largely quiescent in terms of transcriptional and
      translational activity. As a result, once it has left the male reproductive
      tract, the sperm cell is essentially operating with a static population of
      proteins. It therefore is theoretically possible to understand the protein
      networks contained in a sperm cell and to deduce its cellular function
      capabilities. To this end, we performed a proteomic analysis of mouse sperm
      isolated from the cauda epididymis and confidently identified 2850 proteins,
      which to our knowledge is the most comprehensive sperm proteome for any species
      reported to date. These proteins comprise many complete cellular pathways,
      including those for energy production via glycolysis, beta-oxidation and
      oxidative phosphorylation, protein folding and transport, and cell signaling
      systems. This proteome should prove a useful tool for assembly and testing of
      protein networks important for sperm function.

PMID- 23115269
TI  - Involvement of bicarbonate-induced radical signaling in oxysterol formation and
      sterol depletion of capacitating mammalian sperm during in vitro fertilization.
AB  - This study demonstrates for the first time that porcine and mouse sperm incubated
      in capacitation media supplemented with bicarbonate produce oxysterols. The
      production is dependent on a reactive oxygen species (ROS) signaling pathway that
      is activated by bicarbonate and can be inhibited or blocked by addition of
      vitamin E or vitamin A or induced in absence of bicarbonate with pro-oxidants.
      The oxysterol formation was required to initiate albumin dependent depletion of
      30% of the total free sterol and >50% of the formed oxysterols. Incubation of
      bicarbonate treated sperm with oxysterol-binding proteins (ORP-1 or ORP-2) caused
      a reduction of >70% of the formed oxysterols in the sperm pellet but no free
      sterol depletion. Interestingly, both ORP and albumin treatments led to similar
      signs of sperm capacitation: hyperactivated motility, tyrosin phosphorylation,
      and aggregation of flotillin in the apical ridge area of the sperm head. However,
      only albumin incubations led to high in vitro fertilization rates of the oocytes,
      whereas the ORP-1 and ORP-2 incubations did not. A pretreatment of sperm with
      vitamin E or A caused reduced in vitro fertilization rates with 47% and 100%,
      respectively. Artificial depletion of sterols mediated by methyl-beta
      cyclodextrin bypasses the bicarbonate ROS oxysterol signaling pathway but
      resulted only in low in vitro fertilization rates and oocyte degeneration. Thus,
      bicarbonate-induced ROS formation causes at the sperm surface oxysterol formation
      and a simultaneous activation of reverse sterol transport from the sperm surface,
      which appears to be required for efficient oocyte fertilization.

PMID- 23115270
TI  - The role of extracellular matrix metalloproteinase inducer (EMMPRIN) in the
      regulation of bovine endometrial cell functions.
AB  - Extracellular matrix metalloproteinase inducer (EMMPRIN) is a cell surface
      glycoprotein that stimulates the production of several matrix metalloproteinases
      (MMPs) for tissue remodeling. Previously, we detected EMMPRIN in the bovine
      endometrium, and it is mainly expressed in the luminal and glandular epithelium
      whereas MMPs are expressed in the underlying stroma. From this expression
      pattern, we hypothesized that EMMPRIN may regulate stromal MMPs in endometrial
      cell functions. To test this hypothesis, a coculture of epithelial and stromal
      cells was performed using a transwell system. In the coculture, epithelial cells
      were cultured on the insert membrane and stromal cell on the surface of well
      plates. Expression of stromal MMP-2 and MMP-14 was significantly higher in
      coculture with epithelial cell. Further, with the addition of anti-EMMPRIN
      antibody into the epithelial cell compartment, the expression of stromal EMMPRIN
      and MMP-2 and MMP-14 was decreased. To identify the active site of EMMPRIN for
      the augmentation of MMPs, EMMPRIN synthetic peptides that correspond to the
      extracellular loop domain-I (EM1, EM2, EM3, and EM4) were added into the
      epithelial cell compartment, and only EM2 at a higher dose interfered with
      EMMPRIN-mediated expression of MMP-14. Next, we examined the effects of
      progesterone and/or estrogen on the expression of EMMPRIN, MMP-2, and MMP-14.
      Progesterone (300 nM) significantly stimulated the expression of EMMPRIN but had
      no effects on any of the MMPs. These results suggest that EMMPRIN derived from
      epithelial cells regulates MMPs in the endometrium under progesterone-rich
      conditions and may thereby modulate bovine endometrial cell functions during
      gestation.

PMID- 23115271
TI  - Targeted loss of androgen receptor signaling in murine granulosa cells of
      preantral and antral follicles causes female subfertility.
AB  - Ovarian granulosa cells display strong androgen receptor (AR) expression,
      suggesting a functional role for direct AR-mediated actions within developing
      mammalian follicles. By crossing AR-floxed and anti-Mullerian hormone (AMH)-Cre
      recombinase mice, we generated granulosa cell-specific androgen receptor knockout
      mice (GCARKO). Cre expression, assessed by lacZ activity, localized to 70%-100%
      of granulosa cells in most preantral to antral follicles, allowing for selected
      evaluation of granulosa cell AR-dependent actions during follicle development.
      Relative to wild-type (WT) females, GCARKO females were subfertile, producing a
      24% reduction in the number of litters (P < 0.05) over 6 mo and an age-dependent
      decrease in total number of pups born, evident from 6 mo of age (P < 0.05).
      Follicle dynamics were altered in GCARKO ovaries at 3 mo of age, with a
      significant reduction in large preantral and small antral follicle numbers
      compared to WT ovaries (P < 0.05). Global premature follicle depletion was not
      observed, but increased follicular atresia was evident in GCARKO ovaries at 6 mo
      of age, with an 81% increase in unhealthy follicles and zona pellucida remnants
      (P < 0.01). Cumulus cell expansion was decreased (P < 0.01) and oocyte viability
      was diminished in GCARKO females, with a significant reduction in the percentage
      of oocytes fertilized after natural mating and, thus, in the rate of progression
      to the two-cell embryo stage (P < 0.05). In addition, compared with age-matched
      WT females, 6-mo-old GCARKO females exhibited significantly prolonged estrous
      cycles (P <= 0.05), suggesting altered hypothalamic-pituitary-gonadal feedback
      signaling. In conclusion, our findings revealed that selective loss of granulosa
      cell AR actions during preantral and antral stages of development leads to a
      premature reduction in female fecundity through reduced follicle health and
      oocyte viability.

PMID- 23115272
TI  - Impaired ribosomal subunit association in Shwachman-Diamond syndrome.
AB  - Shwachman-Diamond syndrome (SDS) is an autosomal-recessive marrow failure
      syndrome with a predisposition to leukemia. SDS patients harbor biallelic
      mutations in the SBDS gene, resulting in low levels of SBDS protein. Data from
      nonhuman models demonstrate that the SBDS protein facilitates the release of
      eIF6, a factor that prevents ribosome joining. The complete abrogation of Sbds
      expression in these models results in severe cellular and lethal physiologic
      abnormalities that differ from the human disease phenotype. Because human SDS
      cells are characterized by partial rather than complete loss of SBDS expression,
      we interrogated SDS patient cells for defects in ribosomal assembly. SDS patient
      cells exhibit altered ribosomal profiles and impaired association of the 40S and
      60S subunits. Introduction of a wild-type SBDS cDNA into SDS patient cells
      corrected the ribosomal association defect, while patient-derived SBDS point
      mutants only partially improved subunit association. Knockdown of eIF6 expression
      improved ribosomal subunit association but did not correct the hematopoietic
      defect of SBDS-deficient cells. In summary, we demonstrate an SBDS-dependent
      ribosome maturation defect in SDS patient cells. The role of ribosomal subunit
      joining in marrow failure warrants further investigation.

PMID- 23115273
TI  - Divergent effects of supraphysiologic Notch signals on leukemia stem cells and
      hematopoietic stem cells.
AB  - The leukemia stem cell (LSC) hypothesis proposes that a subset of cells in the
      bulk leukemia population propagates the leukemia.We tested the LSC hypothesis in
      a mouse model of Notch-induced T-cell acute lymphoblastic leukemia (T-ALL) in
      which the tumor cells were largely CD4+ CD8+ T cells. LSC activity was enriched
      but rare in the CD8+ CD4 HSA(hi) immature single-positive T-cell subset. Although
      our murine T-ALL model relies on transduction of HSCs, we were unable to isolate
      Notch-activated HSCs to test for LSC activity. Further analysis showed that Notch
      activation in HSCs caused an initial expansion of hematopoietic and T-cell
      progenitors and loss of stem cell quiescence, which was followed by progressive
      loss of long-term HSCs and T-cell production over several weeks. Similar results
      were obtained in a conditional transgenic model in which Notch activation is
      induced in HSCs by Cre recombinase. We conclude that although supraphysiologic
      Notch signaling in HSCs promotes LSC activity in T-cell progenitors, it
      extinguishes self-renewal of LT-HSCs. These results provide further evidence for
      therapeutically targeting T-cell progenitors in T-ALL while also underscoring the
      need to tightly regulate Notch signaling to expand normal HSC populations for
      clinical applications.

PMID- 23115274
TI  - Secondary genetic lesions in acute myeloid leukemia with inv(16) or t(16;16): a
      study of the German-Austrian AML Study Group (AMLSG).
AB  - In this study, we evaluated the impact of secondary genetic lesions in acute
      myeloid leukemia (AML) with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11.
      We studied 176 patients, all enrolled on prospective treatment trials, for
      secondary chromosomal aberrations and mutations in N-/KRAS, KIT, FLT3, and JAK2
      (V617F) genes. Most frequent chromosomal aberrations were trisomy 22 (18%) and
      trisomy 8 (16%). Overall, 84% of patients harbored at least 1 gene mutation, with
      RAS being affected in 53% (45% NRAS; 13% KRAS) of the cases, followed by KIT
      (37%) and FLT3 (17%; FLT3-TKD [14%], FLT3-ITD [5%]). None of the secondary
      genetic lesions influenced achievement of complete remission. In multivariable
      analyses, KIT mutation (hazard ratio [HR] = 1.67; P = .04], log(10)(WBC) (HR =
      1.33; P = .02), and trisomy 22 (HR = 0.54; P = .08) were relevant factors for
      relapse-free survival; for overall survival, FLT3 mutation (HR = 2.56; P = .006),
      trisomy 22 (HR = 0.45; P = .07), trisomy 8 (HR = 2.26; P = .02), age (difference
      of 10 years, HR = 1.46; P = .01), and therapy-related AML (HR = 2.13; P = .14)
      revealed as prognostic factors. The adverse effects of KIT and FLT3 mutations
      were mainly attributed to exon 8 and tyrosine kinase domain mutations,
      respectively. Our large study emphasizes the impact of both secondary chromosomal
      aberrations as well as gene mutations for outcome in AML with inv(16)/t (16;16).

PMID- 23115275
TI  - Macropinocytosis-like HIV-1 internalization in macrophages is CCR5 dependent and
      leads to efficient but delayed degradation in endosomal compartments.
AB  - HIV-1 endocytosis by a macropinocytosis-like mechanism has been shown to lead to
      productive infection in macrophages. However, little is known of this pathway. In
      this study, we examined HIV-1 endocytosis using biochemical approaches and
      imaging techniques in order to better understand the mechanisms that allow for
      productive infection of these cells via the endosomal pathway. We show here that
      this macropinocytosis-like mechanism is not the sole pathway involved in HIV-1
      endocytosis in macrophages. However, this pathway specifically requires CCR5
      engagement at the cell surface, which in turn suggests that the virus and its
      coreceptor are present in the endosomal environment simultaneously. Furthermore,
      although we observed efficient viral degradation following endocytosis, analyses
      of HIV-1 transport through the endolysosomal pathway revealed that viral
      degradation is delayed following endosomal internalization, possibly allowing the
      virus to complete its fusion.

PMID- 23115276
TI  - Stress granule formation induced by measles virus is protein kinase PKR dependent
      and impaired by RNA adenosine deaminase ADAR1.
AB  - ADAR1, an interferon (IFN)-inducible double-stranded (ds) RNA-specific adenosine
      deaminase, downregulates host innate responses, including activation of the dsRNA
      dependent protein kinase (PKR) and induction of IFN-beta mRNA. Conversely, PKR
      amplifies IFN-beta induction by measles virus (MV) and inhibits virus protein
      synthesis. Formation of stress granules (SGs), cytoplasmic aggregates of stalled
      translation complexes and RNA-binding proteins, is a host response to virus
      infection mediated by translation initiation factor eIF2alpha phosphorylation. We
      examined the roles of PKR and ADAR1 in SG formation using HeLa cells stably
      deficient in either PKR (PKR(kd)) or ADAR1 (ADAR1(kd)) compared to control
      (CON(kd)) cells. Infection with either wild-type (WT) MV or an isogenic mutant
      lacking C protein expression (C(ko)) comparably induced formation of SG in
      ADAR1(kd) cells, whereas only the C(ko) mutant was an efficient inducer in
      control cells. Both ADAR1 and PKR colocalized with SG following infection. MV
      induced; SG formation was PKR dependent but impaired by ADAR1. Complementation of
      ADAR1(kd) cells by expression of either p150 WT isoform or the p150 Zalpha
      (Y177A) Z-DNA-binding mutant of ADAR1 restored suppression of host responses,
      including SG formation and PKR activation. In contrast, neither the p110 WT
      isoform nor the p150 catalytic (H910A, E912A) mutant of ADAR1 complemented the
      ADAR1(kd) phenotype. These results further establish ADAR1 as a suppressor of
      host innate responses, including activation of PKR and the subsequent SG
      response.

PMID- 23115277
TI  - Antiviral therapy can reverse the development of immune senescence in elderly
      mice with latent cytomegalovirus infection.
AB  - Cytomegalovirus (CMV) infection leads to the development of adaptive and humoral
      immune responses that are among the largest for any pathogen, and intriguingly,
      the magnitude of the immune response increases with age, a phenomenon termed
      "memory inflation." Elevated CMV-specific immunity has been correlated with an
      increased mortality rate in elderly individuals and with impaired vaccination
      responses. The latent phase of CMV infection is characterized by intermittent
      episodes of subclinical viral reactivation and the production of immunogenic
      transcripts that may maintain memory inflation of virus-specific cytotoxic
      lymphocytes. However, the relative importance of CMV reactivation in the
      development of memory inflation is uncertain, as is the potential for antiviral
      treatment to reverse this effect. Here, we administered valaciclovir for up to 12
      months in mice with established murine CMV (MCMV) infection. Treatment reduced
      the magnitude of the MCMV-specific CD8(+) T-lymphocyte response by 80%, and the
      residual MCMV tetramer-specific lymphocytes exhibited a less differentiated
      phenotype. In addition, latent MCMV infection suppressed the proportion of naive
      CD8(+) T cells by 60% compared to antiviral-treated mice or MCMV-negative
      animals. Furthermore, treatment led to a reduction in influenza A viral loads
      following a challenge in elderly MCMV-infected animals and also reduced the
      differentiation of influenza virus-specific cytotoxic lymphocytes. These
      observations demonstrate that MCMV-specific memory inflation is maintained by
      viral replication and that therapeutic intervention could lead to improved immune
      function.

PMID- 23115278
TI  - Functional and structural characterization of neutralizing epitopes of measles
      virus hemagglutinin protein.
AB  - Effective vaccination programs have dramatically reduced the number of measles
      related deaths globally. Although all the available data suggest that measles
      eradication is biologically feasible, a structural and biochemical basis for the
      single serotype nature of measles virus (MV) remains to be provided. The
      hemagglutinin (H) protein, which binds to two discrete proteinaceous receptors,
      is the major neutralizing target. Monoclonal antibodies (MAbs) recognizing
      distinct epitopes on the H protein were characterized using recombinant MVs
      encoding the H gene from different MV genotypes. The effects of various mutations
      on neutralization by MAbs and virus fitness were also analyzed, identifying the
      location of five epitopes on the H protein structure. Our data in the present
      study demonstrated that the H protein of MV possesses at least two conserved
      effective neutralizing epitopes. One, which is a previously recognized epitope,
      is located near the receptor-binding site (RBS), and thus MAbs that recognize
      this epitope blocked the receptor binding of the H protein, whereas the other
      epitope is located at the position distant from the RBS. Thus, a MAb that
      recognizes this epitope did not inhibit the receptor binding of the H protein,
      rather interfered with the hemagglutinin-fusion (H-F) interaction. This epitope
      was suggested to play a key role for formation of a higher order of an H-F
      protein oligomeric structure. Our data also identified one nonconserved effective
      neutralizing epitope. The epitope has been masked by an N-linked sugar
      modification in some genotype MV strains. These data would contribute to our
      understanding of the antigenicity of MV and support the global elimination
      program of measles.

PMID- 23115279
TI  - Epigenetic silencing of antiviral genes renders clones of Huh-7 cells permissive
      for hepatitis C virus replication.
AB  - Hepatitis C virus (HCV) does not replicate efficiently in wild-type human
      hepatoma Huh-7 cells, but it replicates robustly in certain subclones of Huh-7
      cells. Previously, we demonstrated that silencing of cyclic AMP (cAMP) response
      element binding protein 3-like 1 (CREB3L1), a cellular transcription factor that
      inhibits HCV replication, allows HCV to replicate in HRP1 cells, a subclone of
      Huh-7 cells permissive for HCV replication. Here we show that silencing of
      myxovirus resistant 1 (MX1), a known interferon-induced antiviral gene, is
      responsible for HRP4 cells, another subclone of Huh-7 cells, being permissive for
      HCV replication. Both CREB3L1 and MX1 are epigenetically silenced through DNA
      methylation in HRP1 and HRP4 cells, respectively. We further demonstrate that Huh
      7 cells exist as a mixed population of cells with distinct patterns of gene
      methylation and HCV replicates in subpopulations of Huh-7 cells that have
      antiviral genes epigenetically silenced by DNA hypermethylation. Our results
      demonstrate that understanding the mechanism through which subclones of Huh-7
      cells become permissive for HCV replication is crucial for studying their
      interaction with HCV.

PMID- 23115280
TI  - A second CRM1-dependent nuclear export signal in the influenza A virus NS2
      protein contributes to the nuclear export of viral ribonucleoproteins.
AB  - Influenza A virus NS2 protein, also called nuclear export protein (NEP), is
      crucial for the nuclear export of viral ribonucleoproteins. However, the
      molecular mechanisms of NEP mediation in this process remain incompletely
      understood. A leucine-rich nuclear export signal (NES2) in NEP, located at the
      predicted N2 helix of the N-terminal domain, was identified in the present study.
      NES2 was demonstrated to be a transferable NES, with its nuclear export activity
      depending on the nuclear export receptor chromosome region maintenance 1 (CRM1)
      mediated pathway. The interaction between NEP and CRM1 is coordinately regulated
      by both the previously reported NES (NES1) and now the new NES2. Deletion of the
      NES1 enhances the interaction between NEP and CRM1, and deletion of the NES1 and
      NES2 motifs completely abolishes this interaction. Moreover, NES2 interacts with
      CRM1 in the mammalian two-hybrid system. Mutant viruses containing NES2
      alterations generated by reversed genetics exhibit reduced viral growth and delay
      in the nuclear export of viral ribonucleoproteins (vRNPs). The NES2 motif is
      highly conserved in the influenza A and B viruses. The results demonstrate that
      leucine-rich NES2 is involved in the nuclear export of vRNPs and contributes to
      the understanding of nucleocytoplasmic transport of influenza virus vRNPs.

PMID- 23115281
TI  - The viral interferon regulatory factors of kaposi's sarcoma-associated
      herpesvirus differ in their inhibition of interferon activation mediated by toll
      like receptor 3.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) infection is correlated with three
      human malignancies and can establish lifelong latent infection in multiple cell
      types within its human host. In order to establish and maintain infection, KSHV
      utilizes multiple mechanisms to evade the host immune response. One such
      mechanism is the expression of a family of genes with homology to cellular
      interferon (IFN) regulatory factors (IRFs), known as viral IRFs (vIRFs). We
      demonstrate here that KSHV vIRF1, -2, and -3 have a differential ability to block
      type I interferon signaling mediated by Toll-like receptor 3 (TLR3), a receptor
      we have previously shown to be activated upon KSHV infection. vIRF1, -2, and -3
      inhibited TLR3-driven activation of IFN transcription reporters. However, only
      vIRF1 and vIRF2 inhibited increases in both IFN-beta message and protein levels
      following TLR3 activation. The expression of vIRF1 and vIRF2 also allowed for
      increased replication of a virus known to activate TLR3 signaling. Furthermore,
      vIRF1 and vIRF2 may block TLR3-mediated signaling via different mechanisms.
      Altogether, this report indicates that vIRFs are able to block IFN mediated by
      TLRs but that each vIRF has a unique function and mechanism for blocking
      antiviral IFN responses.

PMID- 23115282
TI  - Fixation of emerging interviral recombinants in cucumber mosaic virus
      populations.
AB  - Interstrain recombinants were observed in the progenies of the Cucumber mosaic
      virus (CMV) reassortant L(1)L(2)F(3) containing RNAs 1 and 2 from LS-CMV and RNA
      3 from Fny-CMV. We characterized these recombinants, and we found that their
      fixation was controlled by the nature of the replicating RNAs 1 and 2. We
      demonstrate that the 2b gene partially affects this fixation process, but only in
      the context of homologous RNAs 1 and 2.

PMID- 23115283
TI  - Mapping viral functional domains for genetic diversity in plants.
AB  - Cucumber mosaic virus (CMV) comprises numerous isolates with various levels of in
      host diversity. Subgroup-distinctive features of the Fny and LS strains provided
      us with a platform to genetically map the viral control elements for genetic
      variation in planta. We found that both RNAs 1 and 2 controlled levels of genetic
      diversity, and further fine mapping revealed that the control elements of
      mutation frequency reside within the first 596 amino acids (aa) of RNA 1. The
      2a/2b overlapping region of the 2a protein also contributed to control of viral
      genetic variation. Furthermore, the 3' nontranslated region (NTR) of RNA 3
      constituted a hot spot of polymorphism, where the majority of fixed mutations
      found in the population were clustered. The 2b gene of CMV, a viral suppressor of
      gene silencing, controls the abundance of the fixed mutants in the viral
      population via a host-dependent mechanism.

PMID- 23115284
TI  - Comprehensive mutational analysis reveals p6Gag phosphorylation to be dispensable
      for HIV-1 morphogenesis and replication.
AB  - The structural polyprotein Gag of human immunodeficiency virus type 1 (HIV-1) is
      necessary and sufficient for formation of virus-like particles. Its C-terminal p6
      domain harbors short peptide motifs that facilitate virus release from the plasma
      membrane and mediate incorporation of the viral Vpr protein. p6 has been shown to
      be the major viral phosphoprotein in HIV-1-infected cells and virions, but the
      sites and functional relevance of p6 phosphorylation are not clear. Here, we
      identified phosphorylation of several serine and threonine residues in p6 in
      purified virus preparations using mass spectrometry. Mutation of individual
      candidate phosphoacceptor residues had no detectable effect on virus assembly,
      release, and infectivity, however, suggesting that phosphorylation of single
      residues may not be functionally relevant. Therefore, a comprehensive mutational
      analysis was conducted changing all potentially phosphorylatable amino acids in
      p6, except for a threonine that is part of an essential peptide motif. To avoid
      confounding changes in the overlapping pol reading frame, mutagenesis was
      performed in a provirus with genetically uncoupled gag and pol reading frames. An
      HIV-1 derivative carrying 12 amino acid changes in its p6 region, abolishing all
      but one potential phosphoacceptor site, showed no impairment of Gag assembly and
      virus release and displayed only very subtle deficiencies in viral infectivity in
      T-cell lines and primary lymphocytes. All mutations were stable over 2 weeks of
      culture in primary cells. Based on these findings, we conclude that
      phosphorylation of p6 is dispensable for HIV-1 assembly, release, and infectivity
      in tissue culture.

PMID- 23115285
TI  - Cumulative impact of host and viral factors on HIV-1 viral-load control during
      early infection.
AB  - In HIV-1 infection, the early set-point viral load strongly predicts both viral
      transmission and disease progression. The factors responsible for the wide
      spectrum of set-point viral loads are complex and likely reflect an interplay
      between the transmitted virus and genetically defined factors in both the
      transmitting source partner and the seroconverter. Indeed, analysis of 195
      transmission pairs from Lusaka, Zambia, revealed that the viral loads in
      transmitting source partners contributed only ~2% of the variance in early set
      point viral loads of seroconverters (P = 0.046 by univariable analysis). In
      multivariable models, early set-point viral loads in seroconverting partners were
      a complex function of (i) the viral load in the source partner, (ii) the gender
      of the seroconverter, (iii) specific HLA class I alleles in the newly infected
      partner, and (iv) sharing of HLA-I alleles between partners in a transmission
      pair. Each of these factors significantly and independently contributed to the
      set-point viral load in the newly infected partner, accounting for up to 37% of
      the variance observed and suggesting that many factors operate in concert to
      define the early virological phenotype in HIV-1 infection.

PMID- 23115286
TI  - Rotavirus viroplasm proteins interact with the cellular SUMOylation system:
      implications for viroplasm-like structure formation.
AB  - Posttranslational modification by SUMO provides functional flexibility to target
      proteins. Viruses interact extensively with the cellular SUMO modification system
      in order to improve their replication, and there are numerous examples of viral
      proteins that are SUMOylated. However, thus far the relevance of SUMOylation for
      rotavirus replication remains unexplored. In this study, we report that
      SUMOylation positively regulates rotavirus replication and viral protein
      production. We show that SUMO can be covalently conjugated to the viroplasm
      proteins VP1, VP2, NSP2, VP6, and NSP5. In addition, VP1, VP2, and NSP2 can also
      interact with SUMO in a noncovalent manner. We observed that an NSP5 SUMOylation
      mutant protein retains most of its activities, such as its interaction with VP1
      and NSP2, the formation of viroplasm-like structures after the coexpression with
      NSP2, and the ability to complement in trans the lack of NSP5 in infected cells.
      However, this mutant is characterized by a high degree of phosphorylation and is
      impaired in the formation of viroplasm-like structures when coexpressed with VP2.
      These results reveal for the first time a positive role for SUMO modification in
      rotavirus replication, describe the SUMOylation of several viroplasm resident
      rotavirus proteins, and demonstrate a requirement for NSP5 SUMOylation in the
      production of viroplasm-like structures.

PMID- 23115287
TI  - Sequential seasonal H1N1 influenza virus infections protect ferrets against novel
      2009 H1N1 influenza virus.
AB  - Individuals <60 years of age had the lowest incidence of infection, with ~25% of
      these people having preexisting, cross-reactive antibodies to novel 2009 H1N1
      influenza. Many people >60 years old also had preexisting antibodies to novel
      H1N1. These observations are puzzling because the seasonal H1N1 viruses
      circulating during the last 60 years were not antigenically similar to novel
      H1N1. We therefore hypothesized that a sequence of exposures to antigenically
      different seasonal H1N1 viruses can elicit an antibody response that protects
      against novel 2009 H1N1. Ferrets were preinfected with seasonal H1N1 viruses and
      assessed for cross-reactive antibodies to novel H1N1. Serum from infected ferrets
      was assayed for cross-reactivity to both seasonal and novel 2009 H1N1 strains.
      These results were compared to those of ferrets that were sequentially infected
      with H1N1 viruses isolated prior to 1957 or more-recently isolated viruses.
      Following seroconversion, ferrets were challenged with novel H1N1 influenza virus
      and assessed for viral titers in the nasal wash, morbidity, and mortality. There
      was no hemagglutination inhibition (HAI) cross-reactivity in ferrets infected
      with any single seasonal H1N1 influenza viruses, with limited protection to
      challenge. However, sequential H1N1 influenza infections reduced the incidence of
      disease and elicited cross-reactive antibodies to novel H1N1 isolates. The amount
      and duration of virus shedding and the frequency of transmission following novel
      H1N1 challenge were reduced. Exposure to multiple seasonal H1N1 influenza
      viruses, and not to any single H1N1 influenza virus, elicits a breadth of
      antibodies that neutralize novel H1N1 even though the host was never exposed to
      the novel H1N1 influenza viruses.

PMID- 23115288
TI  - SNX17 facilitates infection with diverse papillomavirus types.
AB  - Previous studies have shown that the human papillomavirus type 16 (HPV-16) L2
      capsid protein plays an essential role in viral infection, in part through its
      interaction with sorting nexin 17 (SNX17). We now show that this interaction
      between L2 and SNX17 is conserved across multiple PV types. Furthermore, we
      demonstrate that SNX17 is essential for infection with all PV types analyzed,
      indicating an evolutionarily highly conserved virus entry mechanism.

PMID- 23115289
TI  - Comparative proteomics reveal fundamental structural and functional differences
      between the two progeny phenotypes of a baculovirus.
AB  - The replication of lepidopteran baculoviruses is characterized by the production
      of two progeny phenotypes: the occlusion-derived virus (ODV), which establishes
      infection in midgut cells, and the budded virus (BV), which disseminates
      infection to different tissues within a susceptible host. To understand the
      structural, and hence functional, differences between BV and ODV, we employed
      multiple proteomic methods to reveal the protein compositions and
      posttranslational modifications of the two phenotypes of Helicoverpa armigera
      nucleopolyhedrovirus. In addition, Western blotting and quantitative mass
      spectrometry were used to identify the localization of proteins in the envelope
      or nucleocapsid fractions. Comparative protein portfolios of BV and ODV showing
      the distribution of 54 proteins, encompassing the 21 proteins shared by BV and
      ODV, the 12 BV-specific proteins, and the 21 ODV-specific proteins, were
      obtained. Among the 11 ODV-specific envelope proteins, 8 either are essential for
      or contribute to oral infection. Twenty-three phosphorylated and 6 N-glycosylated
      viral proteins were also identified. While the proteins that are shared by the
      two phenotypes appear to be important for nucleocapsid assembly and trafficking,
      the structural and functional differences between the two phenotypes are
      evidently characterized by the envelope proteins and posttranslational
      modifications. This comparative proteomics study provides new insight into how BV
      and ODV are formed and why they function differently.

PMID- 23115290
TI  - Seasonal trivalent inactivated influenza vaccine does not protect against newly
      emerging variants of influenza A (H3N2v) virus in ferrets.
AB  - The recent increase in human cases of influenza A H3N2 variant virus [A(H3N2)v]
      highlights the need to assess whether seasonal influenza vaccination provides
      cross-protection against A(H3N2)v virus. Our data demonstrate that the 2011-2012
      trivalent inactivated influenza vaccine (TIV) protected ferrets against
      homologous H3N2 virus challenge but provided minimal to no protection against
      A(H3N2)v virus. The complete absence of specific hemagglutination inhibition
      antibody response to A(H3N2)v is consistent with the poor cross-protection
      observed among TIV-immune animals.

PMID- 23115291
TI  - Crystal structure of the cowpox virus-encoded NKG2D ligand OMCP.
AB  - The NKG2D receptor is expressed on the surface of NK, T, and macrophage lineage
      cells and plays an important role in antiviral and antitumor immunity. To evade
      NKG2D recognition, herpesviruses block the expression of NKG2D ligands on the
      surface of infected cells using a diverse repertoire of sabotage methods. Cowpox
      and monkeypox viruses have taken an alternate approach by encoding a soluble
      NKG2D ligand, the orthopoxvirus major histocompatibility complex (MHC) class I
      like protein (OMCP), which can block NKG2D-mediated cytotoxicity. This approach
      has the advantage of targeting a single conserved receptor instead of numerous
      host ligands that exhibit significant sequence diversity. Here, we show that OMCP
      binds the NKG2D homodimer as a monomer and competitively blocks host ligand
      engagement. We have also determined the 2.25-A-resolution crystal structure of
      OMCP from the cowpox virus Brighton Red strain, revealing a truncated MHC class I
      like platform domain consisting of a beta sheet flanked with two antiparallel
      alpha helices. OMCP is generally similar in structure to known host NKG2D ligands
      but has notable variations in regions typically used to engage NKG2D.
      Additionally, the determinants responsible for the 14-fold-higher affinity of
      OMCP for human than for murine NKG2D were mapped to a single loop in the NKG2D
      ligand-binding pocket.

PMID- 23115292
TI  - A hepatitis C virus NS5A phosphorylation site that regulates RNA replication.
AB  - The hepatitis C virus NS5A protein is essential for RNA replication and virion
      assembly. NS5A is phosphorylated on multiple residues during infections, but
      these sites remain uncharacterized. Here we identify serine 222 of genotype 2a
      NS5A as a phosphorylation site that functions as a negative regulator of RNA
      replication. This site is a component of the hyperphosphorylated form of NS5A,
      which is in good agreement with previous observations that hyperphosphorylation
      negatively affects replication.

PMID- 23115293
TI  - AMP-activated protein kinase is required for the macropinocytic internalization
      of ebolavirus.
AB  - Identification of host factors that are needed for Zaire Ebolavirus (EBOV) entry
      provides insights into the mechanism(s) of filovirus uptake, and these factors
      may serve as potential antiviral targets. In order to identify novel host genes
      and pathways involved in EBOV entry, gene array findings in the National Cancer
      Institute's NCI-60 panel of human tumor cell lines were correlated with
      permissivity for EBOV glycoprotein (GP)-mediated entry. We found that the gene
      encoding the gamma2 subunit of AMP-activated protein kinase (AMPK) strongly
      correlated with EBOV transduction in the tumor panel. The AMPK inhibitor compound
      C inhibited infectious EBOV replication in Vero cells and diminished EBOV GP
      dependent, but not Lassa fever virus GPC-dependent, entry into a variety of cell
      lines in a dose-dependent manner. Compound C also prevented EBOV GP-mediated
      infection of primary human macrophages, a major target of filoviral replication
      in vivo. Consistent with a role for AMPK in filovirus entry, time-of-addition
      studies demonstrated that compound C abrogated infection when it was added at
      early time points but became progressively less effective when added later.
      Compound C prevented EBOV pseudovirion internalization at 37 degrees C as cell
      bound particles remained susceptible to trypsin digestion in the presence of the
      inhibitor but not in its absence. Mouse embryonic fibroblasts lacking the
      AMPKalpha1 and AMPKalpha2 catalytic subunits were significantly less permissive
      to EBOV GP-mediated infection than their wild-type counterparts, likely due to
      decreased macropinocytic uptake. In total, these findings implicate AMPK in
      macropinocytic events needed for EBOV GP-dependent entry and identify a novel
      cellular target for new filoviral antivirals.

PMID- 23115294
TI  - Minimum requirements for bluetongue virus primary replication in vivo.
AB  - The replication mechanism of bluetongue virus (BTV) has been studied by an in
      vivo reverse genetics (RG) system identifying the importance of certain BTV
      proteins for primary replication of the virus. However, a unique in vitro cell
      free virus assembly system was subsequently developed, showing that it did not
      require the same set of viral components, which is indicative of differences in
      these two systems. Here, we studied the in vivo primary replicase complex more in
      depth to determine the minimum components of the complex. We showed that while
      NS2 is an essential component of the primary replication stage during BTV
      infection, NS1 is not an essential component but may play a role in enhancing BTV
      protein synthesis. Furthermore, we demonstrated that VP7, a major structural
      protein of the inner core, is not required for primary replication but appears to
      stabilize the replicase complex. In contrast, VP3, the other major structural
      core protein, is an essential component of the complex, together with the three
      minor enzymatic proteins (VP1, VP4, and VP6) of the core. In addition, our data
      have demonstrated that the smallest minor protein, VP6, which is known to possess
      an RNA-dependent helicase activity, may also act as an RNA translocator during
      assembly of the primary replicase complex.

PMID- 23115295
TI  - Inefficient vaginal transmission of tenofovir-resistant HIV-1.
AB  - Transmission of drug-resistant HIV has been postulated to be a threat to current
      first-line antiretroviral therapy (ART) regimens and the efficacy of several
      antiretroviral-based preexposure prophylaxis (PrEP) strategies being tested. Here
      we evaluated the effect of the common tenofovir (TFV) resistance mutation K65R on
      vaginal HIV transmission. Our results demonstrate that despite no overt loss of
      overall replication competence in vivo, this mutation results in significantly
      reduced mucosal transmission. When transmitted, the mutant virus eventually
      reverted to the wild type in 2 of 3 animals examined.

PMID- 23115296
TI  - Structure of the St. Louis encephalitis virus postfusion envelope trimer.
AB  - St. Louis encephalitis virus (SLEV) is a mosquito-borne flavivirus responsible
      for several human encephalitis outbreaks over the last 80 years. Mature
      flavivirus virions are coated with dimeric envelope (E) proteins that mediate
      attachment and fusion with host cells. E is a class II fusion protein, the
      hallmark of which is a distinct dimer-to-trimer rearrangement that occurs upon
      endosomal acidification and insertion of hydrophobic fusion peptides into the
      endosomal membrane. Herein, we report the crystal structure of SLEV E in the
      posfusion trimer conformation. The structure revealed specific features that
      differentiate SLEV E from trimers of related flavi- and alphaviruses. SLEV E
      fusion loops have distinct intermediate spacing such that they are positioned
      further apart than previously observed in flaviviruses but closer together than
      Semliki Forest virus, an alphavirus. Domains II and III (DII and DIII) of SLEV E
      also adopt different angles relative to DI, which suggests that the DI-DII joint
      may accommodate spheroidal motions. However, trimer interfaces are well conserved
      among flaviviruses, so it is likely the differences observed represent structural
      features specific to SLEV function. Analysis of surface potentials revealed a
      basic platform underneath flavivirus fusion loops that may interact with the
      anionic lipid head groups found in membranes. Taken together, these results
      highlight variations in E structure and assembly that may direct virus-specific
      interactions with host determinants to influence pathogenesis.

PMID- 23115297
TI  - The West Nile virus capsid protein blocks apoptosis through a
      phosphatidylinositol 3-kinase-dependent mechanism.
AB  - West Nile virus (WNV) is a mosquito-transmitted pathogen that can cause serious
      disease in humans. Our laboratories are focused on understanding how interactions
      between WNV proteins and host cells contribute to virus replication and
      pathogenesis. WNV replication is relatively slow, and on the basis of earlier
      studies, the virus appears to activate survival pathways that delay host cell
      death during virus replication. The WNV capsid is the first viral protein
      produced in infected cells; however, its role in virus assembly is not required
      until after replication of the genomic RNA. Accordingly, from a temporal
      perspective, it is perfectly suited to block host cell apoptosis during virus
      replication. In the present study, we provide evidence that the WNV capsid
      protein blocks apoptosis through a phosphatidylinositol (PI) 3-kinase-dependent
      pathway. Specifically, expression of this protein in the absence of other viral
      proteins increases the levels of phosphorylated Akt, a prosurvival kinase that
      blocks apoptosis through multiple mechanisms. Treatment of cells with the PI 3
      kinase inhibitor LY294002 abrogates the protective effects of the WNV capsid
      protein.

PMID- 23115298
TI  - Effect of Wolbachia on replication of West Nile virus in a mosquito cell line and
      adult mosquitoes.
AB  - Wolbachia as an endosymbiont is widespread in insects and other arthropods and is
      best known for reproductive manipulations of the host. Recently, it has been
      shown that wMelpop and wMel strains of Wolbachia inhibit the replication of
      several RNA viruses, including dengue virus, and other vector-borne pathogens
      (e.g., Plasmodium and filarial nematodes) in mosquitoes, providing an alternative
      approach to limit the transmission of vector-borne pathogens. In this study, we
      tested the effect of Wolbachia on the replication of West Nile Virus (WNV).
      Surprisingly, accumulation of the genomic RNA of WNV for all three strains of WNV
      tested (New York 99, Kunjin, and New South Wales) was enhanced in Wolbachia
      infected Aedes aegypti cells (Aag2). However, the amount of secreted virus was
      significantly reduced in the presence of Wolbachia. Intrathoracic injections
      showed that replication of WNV in A. aegypti mosquitoes infected with wMel strain
      of Wolbachia was not inhibited, whereas wMelPop strain of Wolbachia significantly
      reduced the replication of WNV in mosquitoes. Further, when wMelPop mosquitoes
      were orally fed with WNV, virus infection, transmission, and dissemination rates
      were very low in Wolbachia-free mosquitoes and were completely inhibited in the
      presence of Wolbachia. The results suggest that (i) despite the enhancement of
      viral genomic RNA replication in the Wolbachia-infected cell line the production
      of secreted virus was significantly inhibited, (ii) the antiviral effect in
      intrathoracically infected mosquitoes depends on the strain of Wolbachia, and
      (iii) replication of the virus in orally fed mosquitoes was completely inhibited
      in wMelPop strain of Wolbachia.

PMID- 23115299
TI  - Unstable polymerase-nucleoprotein interaction is not responsible for avian
      influenza virus polymerase restriction in human cells.
AB  - Avian-origin influenza virus polymerase activity can be dramatically increased in
      human cells with the PB2 E627K mutation. Previously, others have proposed that
      this mutation increases the stability of the viral ribonucleoprotein complex
      (vRNP) measured by the interaction between PB2 and NP. However, we demonstrate
      here that a variety of PB2 adaptive mutations, including E627K, do not enhance
      the stability of the vRNP but rather increase the amount of replicated RNA that
      results in more PB2-NP coprecipitation.

PMID- 23115300
TI  - The herpes simplex virus 1 Us11 protein inhibits autophagy through its
      interaction with the protein kinase PKR.
AB  - Autophagy is now known to be an essential component of host innate and adaptive
      immunity. Several herpesviruses have developed various strategies to evade this
      antiviral host defense. Herpes simplex virus 1 (HSV-1) blocks autophagy in
      fibroblasts and in neurons, and the ICP34.5 protein is important for the
      resistance of HSV-1 to autophagy because of its interaction with the autophagy
      machinery protein Beclin 1. ICP34.5 also counteracts the shutoff of protein
      synthesis mediated by the double-stranded RNA (dsRNA)-dependent protein kinase
      PKR by inhibiting phosphorylation of the eukaryotic translation initiation factor
      2alpha (eIF2alpha) in the PKR/eIF2alpha signaling pathway. Us11 is a late gene
      product of HSV-1, which is also able to preclude the host shutoff by direct
      inhibition of PKR. In the present study, we unveil a previously uncharacterized
      function of Us11 by demonstrating its antiautophagic activity. We show that the
      expression of Us11 is able to block autophagy and autophagosome formation in both
      HeLa cells and fibroblasts. Furthermore, immediate-early expression of Us11 by an
      ICP34.5 deletion mutant virus is sufficient to render the cells resistant to PKR
      induced and virus-induced autophagy. PKR expression and the PKR binding domain of
      Us11 are required for the antiautophagic activity of Us11. However, unlike
      ICP34.5, Us11 did not interact with Beclin 1. We suggest that the inhibition of
      autophagy observed in cells infected with HSV-1 results from the activity of not
      only ICP34.5 on Beclin 1 but also Us11 by direct interaction with PKR.

PMID- 23115301
TI  - A critical assessment of feature selection methods for biomarker discovery in
      clinical proteomics.
AB  - In this paper, we compare the performance of six different feature selection
      methods for LC-MS-based proteomics and metabolomics biomarker discovery-t test,
      the Mann-Whitney-Wilcoxon test (mww test), nearest shrunken centroid (NSC),
      linear support vector machine-recursive features elimination (SVM-RFE), principal
      component discriminant analysis (PCDA), and partial least squares discriminant
      analysis (PLSDA)-using human urine and porcine cerebrospinal fluid samples that
      were spiked with a range of peptides at different concentration levels. The ideal
      feature selection method should select the complete list of discriminating
      features that are related to the spiked peptides without selecting unrelated
      features. Whereas many studies have to rely on classification error to judge the
      reliability of the selected biomarker candidates, we assessed the accuracy of
      selection directly from the list of spiked peptides. The feature selection
      methods were applied to data sets with different sample sizes and extents of
      sample class separation determined by the concentration level of spiked
      compounds. For each feature selection method and data set, the performance for
      selecting a set of features related to spiked compounds was assessed using the
      harmonic mean of the recall and the precision (f-score) and the geometric mean of
      the recall and the true negative rate (g-score). We conclude that the univariate
      t test and the mww test with multiple testing corrections are not applicable to
      data sets with small sample sizes (n = 6), but their performance improves
      markedly with increasing sample size up to a point (n > 12) at which they
      outperform the other methods. PCDA and PLSDA select small feature sets with high
      precision but miss many true positive features related to the spiked peptides.
      NSC strikes a reasonable compromise between recall and precision for all data
      sets independent of spiking level and number of samples. Linear SVM-RFE performs
      poorly for selecting features related to the spiked compounds, even though the
      classification error is relatively low.

PMID- 23115302
TI  - A combined laser microdissection and mass spectrometry approach reveals new
      disease relevant proteins accumulating in aggregates of filaminopathy patients.
AB  - Filaminopathy is a subtype of myofibrillar myopathy caused by mutations in FLNC,
      the gene encoding filamin C, and histologically characterized by pathologic
      accumulation of several proteins within skeletal muscle fibers. With the aim to
      get new insights in aggregate composition, we collected aggregates and control
      tissue from skeletal muscle biopsies of six myofibrillar myopathy patients
      harboring three different FLNC mutations by laser microdissection and analyzed
      the samples by a label-free mass spectrometry approach. A total of 390 proteins
      were identified, and 31 of those showed significantly higher spectral indices in
      aggregates compared with patient controls with a ratio >1.8. These proteins
      included filamin C, other known myofibrillar myopathy associated proteins, and a
      striking number of filamin C binding partners. Across the patients the patterns
      were extremely homogeneous. Xin actin-binding repeat containing protein 2, heat
      shock protein 27, nebulin-related-anchoring protein, and Rab35 could be verified
      as new filaminopathy biomarker candidates. In addition, further experiments
      identified heat shock protein 27 and Xin actin-binding repeat containing protein
      2 as novel filamin C interaction partners and we could show that Xin actin
      binding repeat containing protein 2 and the known interaction partner Xin actin
      binding repeat containing protein 1 simultaneously associate with filamin C. Ten
      proteins showed significant lower spectral indices in aggregate samples compared
      with patient controls (ratio <0.56) including M-band proteins myomesin-1 and
      myomesin-2. Proteomic findings were consistent with previous and novel
      immunolocalization data. Our findings suggest that aggregates in filaminopathy
      have a largely organized structure of proteins also interacting under
      physiological conditions. Different filamin C mutations seem to lead to almost
      identical aggregate compositions. The finding that filamin C was detected as
      highly abundant protein in aggregates in filaminopathy indicates that our
      proteomic approach may be suitable to identify new candidate genes among the many
      MFM patients with so far unknown mutation.

PMID- 23115303
TI  - The RNA-binding protein Y14 inhibits mRNA decapping and modulates processing body
      formation.
AB  - The exon-junction complex (EJC) deposited on a newly spliced mRNA plays an
      important role in subsequent mRNA metabolic events. Here we show that an EJC core
      heterodimer, Y14/Magoh, specifically associates with mRNA-degradation factors,
      including the mRNA-decapping complex and exoribonucleases, whereas another core
      factor, eIF4AIII/MLN51, does not. We also demonstrate that Y14 interacts directly
      with the decapping factor Dcp2 and the 5' cap structure of mRNAs via different
      but overlapping domains and that Y14 inhibits the mRNA-decapping activity of Dcp2
      in vitro. Accordingly, overexpression of Y14 prolongs the half-life of a reporter
      mRNA. Therefore Y14 may function independently of the EJC in preventing mRNA
      decapping and decay. Furthermore, we observe that depletion of Y14 disrupts the
      formation of processing bodies, whereas overexpression of a phosphomimetic Y14
      considerably increases the number of processing bodies, perhaps by sequestering
      the mRNA-degradation factors. In conclusion, this report provides unprecedented
      evidence for a role of Y14 in regulating mRNA degradation and processing body
      formation and reinforces the influence of phosphorylation of Y14 on its activity
      in postsplicing mRNA metabolism.

PMID- 23115304
TI  - Bld10/Cep135 stabilizes basal bodies to resist cilia-generated forces.
AB  - Basal bodies nucleate, anchor, and organize cilia. As the anchor for motile
      cilia, basal bodies must be resistant to the forces directed toward the cell as a
      consequence of ciliary beating. The molecules and generalized mechanisms that
      contribute to the maintenance of basal bodies remain to be discovered.
      Bld10/Cep135 is a basal body outer cartwheel domain protein that has established
      roles in the assembly of nascent basal bodies. We find that Bld10 protein first
      incorporates stably at basal bodies early during new assembly. Bld10 protein
      continues to accumulate at basal bodies after assembly, and we hypothesize that
      the full complement of Bld10 is required to stabilize basal bodies. We identify a
      novel mechanism for Bld10/Cep135 in basal body maintenance so that basal bodies
      can withstand the forces produced by motile cilia. Bld10 stabilizes basal bodies
      by promoting the stability of the A- and C-tubules of the basal body triplet
      microtubules and by properly positioning the triplet microtubule blades. The
      forces generated by ciliary beating promote basal body disassembly in bld10Delta
      cells. Thus Bld10/Cep135 acts to maintain the structural integrity of basal
      bodies against the forces of ciliary beating in addition to its separable role in
      basal body assembly.

PMID- 23115306
TI  - Alveolar macrophages carbon load: a marker of exposure?

PMID- 23115305
TI  - Endoplasmic spreading requires coalescence of vimentin intermediate filaments at
      force-bearing adhesions.
AB  - For cells to develop long-range forces and carry materials to the periphery, the
      microtubule and organelle-rich region at the center of the cell-the endoplasm
      needs to extend to near the cell edge. Depletion of the actin cross-linking
      protein filamin A (FlnA) causes a collapse of the endoplasm into a sphere around
      the nucleus of fibroblasts and disruption of matrix adhesions, indicating that
      FlnA is involved in endoplasmic spreading and adhesion growth. Here, we report
      that treatment with the calpain inhibitor N-[N-(N-acetyl-l-leucyl)-l-leucyl]-l
      norleucine (ALLN) restores endoplasmic spreading as well as focal adhesion (FA)
      growth on fibronectin-coated surfaces in a Fln-depleted background. Addback of
      calpain-uncleavable talin, not full-length talin, achieves a similar effect in
      Fln-depleted cells and indicates a crucial role for talin in endoplasmic
      spreading. Because FA maturation involves the vimentin intermediate filament
      (vIF) network, we also examined the role of vIFs in endoplasmic spreading. Wild
      type cells expressing a vimentin variant incapable of polymerization exhibit
      deficient endoplasmic spreading as well as defects in FA growth. ALLN treatment
      restores FA growth despite the lack of vIFs but does not restore endoplasmic
      spreading, implying that vIFs are essential for endoplasm spreading. Consistent
      with that hypothesis, vIFs are always displaced from adhesions when the endoplasm
      does not spread. In Fln-depleted cells, vIFs extend beyond adhesions, nearly to
      the cell edge. Finally, inhibiting myosin II-mediated contraction blocks
      endoplasmic spreading and adhesion growth. Thus we propose a model in which
      myosin II-mediated forces and coalescence of vIFs at mature FAs are required for
      endoplasmic spreading.

PMID- 23115307
TI  - Neutrophils, airway hyperresponsiveness and COPD: true, true and related?

PMID- 23115308
TI  - Impaired muscle mitochondrial density and/or function: a COPD-specific
      mitochondropathy or simply deconditioning?

PMID- 23115309
TI  - High inhaled corticosteroids adherence in childhood asthma: the role of
      medication beliefs.

PMID- 23115310
TI  - Treating exercise oscillatory ventilation in heart failure: the detail that may
      matter.

PMID- 23115311
TI  - Echocardiography of pulmonary vascular function in asymptomatic carriers of BMPR2
      mutations.

PMID- 23115312
TI  - Diabetes is a risk factor for tuberculosis in the Inuit population of Greenland.

PMID- 23115313
TI  - Outcomes of a tuberculosis contact investigation programme in Italy.

PMID- 23115314
TI  - Influence of ambient air on NMR-based metabolomics of exhaled breath condensates.

PMID- 23115315
TI  - Pleural effusion arising from a rare pancreatic neoplasm.

PMID- 23115316
TI  - Lung toxicity in a patient treated with sunitinib.

PMID- 23115317
TI  - Pregnancy outcomes in pulmonary arterial hypertension in the modern management
      era.

PMID- 23115318
TI  - Chronic bronchitis: an objective diagnosis of exclusion.

PMID- 23115321
TI  - Mutational bias and gene conversion affect the intraspecific nitrogen
      stoichiometry of the Arabidopsis thaliana transcriptome.
AB  - The transcriptome and proteome of Arabidopsis thaliana are reduced in nitrogen
      content when compared with other taxa, which may result from ecological nitrogen
      limitation. We hypothesized that if the A. thaliana transcriptome is selected for
      a low nitrogen content, nitrogen-reducing derived alleles of single nucleotide
      polymorphisms (SNPs) should segregate at higher frequencies than nitrogen
      increasing alleles. This pattern should be stronger in populations with a larger
      effective population size (N(e)) if natural selection is more efficient in large
      than in small populations. We analyzed variation in the nitrogen content in the
      transcriptome of 80 natural accessions of A. thaliana. In contrast to our
      expectations, derived alleles increase the nitrogen content in all accessions,
      and there is a positive correlation between nitrogen difference and derived
      allele frequency, which is strongest with nonsynonymous SNPs (nsSNPs). Also,
      there is a positive correlation between nitrogen difference and N(e) that was
      mainly caused by nsSNPs. These observations led us to reject the hypothesis that
      the transcriptome of A. thaliana is currently under selection to reduce nitrogen
      content. Instead, we show that a change in nitrogen content is a side effect of
      interacting evolutionary factors that influence base composition and include
      mutational bias, purifying selection of functionally deleterious alleles, and GC
      biased gene conversion. We provide strong evidence that GC-biased gene conversion
      may play an important role for base composition in the highly selfing plant A.
      thaliana.

PMID- 23115322
TI  - Association between adrenergic receptor genotypes and beta-blocker dose in heart
      failure patients: analysis from the HF-ACTION DNA substudy.
AB  - AIMS: Beta-blockers reduce morbidity and mortality in chronic heart failure (HF)
      patients with reduced ejection fraction. However, there is heterogeneity in the
      response to these drugs, perhaps due to genetic variations in the beta1
      adrenergic receptor (ADRbeta1). We examined whether the Arg389Gly polymorphism in
      ADRbeta1 interacts with the dose requirements of beta-blockers in patients with
      systolic HF. METHODS AND RESULTS: HF-ACTION was a randomized, multicentre trial
      of ambulatory HF patients with systolic dysfunction who were randomized to
      exercise training or usual care. A subset of patients provided DNA. The
      relationships among beta-blocker dose, ADRbeta1-389 genotype, and outcomes were
      assessed using the Cox proportional hazards regression model. The interaction
      between beta-blocker dose and the ADRbeta1-389 genotype was tested. DNA
      information was available for 957 patients. The alleles did not deviate from
      Hardy-Weinberg equilibrium. Patients with the ADRbeta1-389 Arg/Arg genotype
      receiving low-dose beta-blockers had a two-fold increase in the risk of death
      compared with those receiving a high dose (hazard ratio 2.09; P = 0.015); this
      was not conferred in Gly carriers. There was also an interaction between
      improvements in Kansas City Cardiomyopathy Questionnaire score and beta-blocker
      dose by genotype, suggesting that higher doses of beta-blockade might be needed
      to achieve benefit in Arg/Arg genotype patients. CONCLUSION: There was a gene
      dose interaction with the ADRbeta1-389 Arg/Arg vs. Gly carrier genotype and beta
      blocker dose, suggesting that patients with the Arg/Arg genotype might require a
      higher dose of beta-blockade to achieve a treatment response similar to that of
      Gly carriers.

PMID- 23115323
TI  - Decreased mitochondrial oxidative phosphorylation capacity in the human heart
      with left ventricular systolic dysfunction.
AB  - AIMS: Heart failure (HF) with left ventricular systolic dysfunction (LVSD) is
      associated with a shift in substrate utilization and a compromised energetic
      state. Whether these changes are connected with mitochondrial dysfunction is not
      known. We hypothesized that the cardiac phenotype in LVSD could be caused by
      reduced mitochondrial oxidative phosphorylation (OXPHOS) capacity and reduced
      mitochondrial creatine kinase (miCK) capacity. The study aim was to test
      mitochondrial OXPHOS capacity in LVSD myocardium compared with OXPHOS capacity in
      a comparable patient group without LVSD. METHODS AND RESULTS: Myocardial biopsies
      were obtained from the left ventricle during cardiac valve or left ventricular
      assist device (LVAD) surgery. Patients were stratified according to left
      ventricular ejection fraction (LVEF) into LVSD (LVEF <45%, n = 14) or CONTROL
      (LVEF >45%, n = 15). Mitochondrial respiration was measured in muscle fibres with
      addition of non-fatty acid substrates or octanoyl-l-carnitine, a medium chain
      fatty acid (MCFA). The in situ enzyme capacity of miCK was determined from APD
      titrations in the presence or absence of creatine. Maximal OXPHOS capacity with
      non-fatty acid substrates was lower in the LVSD group compared with the CONTROL
      group (P <= 0.05). ADP sensitivity always increased significantly (P <= 0.05)
      with the addition of creatine, after which the sensitivity was highest (P <=
      0.05) in LVSD compared with CONTROL. The stimulation of OXPHOS from octanoyl-l
      carnitine titrations elicited ~40% lower respiration in LVSD compared with
      CONTROL (P <= 0.05). CONCLUSION: Human LVSD is associated with markedly
      diminished OXPHOS capacity, particularly in MCFA oxidation. This offers a
      candidate mechanism for a compromised energetic state and decreased reliance on
      fatty acid utilization in HF.

PMID- 23115324
TI  - BET bromodomain proteins mediate downstream signaling events following growth
      factor stimulation in human lung fibroblasts and are involved in bleomycin
      induced pulmonary fibrosis.
AB  - Epigenetic alterations, such as histone acetylation, regulate the signaling
      outcomes and phenotypic responses of fibroblasts after growth factor stimulation.
      The bromodomain and extra-terminal domain-containing proteins (Brd) bind to
      acetylated histone residues, resulting in recruitment of components of the
      transcriptional machinery and subsequent gene transcription. Given the central
      importance of fibroblasts in tissue fibrosis, this study sought to determine the
      role of Brd proteins in human lung fibroblasts (LFs) after growth factor
      stimulation and in the murine bleomycin model of lung fibrosis. Using small
      interfering RNA against human Brd2 and Brd4 and pharmacologic Brd inhibitors,
      this study found that Brd2 and Brd4 are essential in mediating the phenotypic
      responses of LFs downstream of multiple growth factor pathways. Growth factor
      stimulation of LFs causes increased histone acetylation, association of Brd4 with
      growth factor-responsive genes, and enhanced transcription of these genes that
      could be attenuated with pharmacologic Brd inhibitors. Of note, lung fibrosis
      induced after intratracheal bleomycin challenge in mice could be prevented by
      pretreatment of animals with pharmacologic inhibitors of Brd proteins. This study
      is the first demonstration of a role for Brd2 and Brd4 proteins in mediating the
      responses of LFs after growth factor stimulation and in driving the induction of
      lung fibrosis in mice in response to bleomycin challenge.

PMID- 23115325
TI  - Hydrogen sulfide as an allosteric modulator of ATP-sensitive potassium channels
      in colonic inflammation.
AB  - The ATP-sensitive potassium channel (K(ATP)) in mouse colonic smooth muscle cell
      is a complex containing a pore-forming subunit (Kir6.1) and a sulfonylurea
      receptor subunit (SUR2B). These channels contribute to the cellular excitability
      of smooth muscle cells and hence regulate the motility patterns in the colon.
      Whole-cell voltage-clamp techniques were used to study the alterations in K(ATP)
      channels in smooth muscle cells in experimental colitis. Colonic inflammation was
      induced in BALB/C mice after intracolonic administration of trinitrobenzene
      sulfonic acid. K(ATP) currents were measured at a holding potential of -60 mV in
      high K(+) external solution. The concentration response to levcromakalim (LEVC),
      a K(ATP) channel opener, was significantly shifted to the left in the inflamed
      smooth-muscle cells. Both the potency and maximal currents induced by LEVC were
      enhanced in inflammation. The EC(50) values in control were 6259 nM (n = 10) and
      422 nM (n = 8) in inflamed colon, and the maximal currents were 9.9 +/- 0.71
      pA/pF (60 MUM) in control and 39.7 +/- 8.8 pA/pF (3 MUM) after inflammation. As
      was seen with LEVC, the potency and efficacy of sodium hydrogen sulfide (NaHS)
      (10-1000 MUM) on K(ATP) currents were significantly greater in inflamed colon
      compared with controls. In control cells, pretreatment with 100 uM NaHS shifted
      the EC(50) for LEV-induced currents from 2838 (n = 6) to 154 (n = 8) nM.
      Sulfhydration of sulfonylurea receptor 2B (SUR2B) was induced by NaHS and colonic
      inflammation. These data suggest that sulfhydration of SUR2B induces allosteric
      modulation of K(ATP) currents in colonic inflammation.

PMID- 23115326
TI  - Urinary and serum biomarkers for the diagnosis of acute kidney injury: an in
      depth review of the literature.
AB  - BACKGROUND: Acute kidney injury (AKI) remains associated with high morbidity and
      mortality, despite progress in medical care. Although the RIFLE (Risk, Injury,
      Failure, Loss, End-Stage Kidney Disease) and AKIN (Acute Kidney Injury Network)
      criteria, based on serum creatinine and urine output, were a step forward in
      diagnosing AKI, a reliable tool to differentiate between true parenchymal and pre
      renal azotaemia in clinical practice is still lacking. In the last decade, many
      papers on the use of new urinary and serum biomarkers for the diagnosis and
      prognostication of AKI have been published. Thus, the question arises which
      biomarker is a reliable differential diagnostic tool under which circumstances.
      METHODS: We searched Medline from inception to April 2012 using medical subject
      heading and text words for AKI and biomarkers [neutrophil gelatinase-associated
      lipocalin (NGAL), kidney injury molecule-1 (KIM-1), Cystatin C, interleukin-6 (IL
      6), interleukin-8 (IL-8), interleukin-18 (IL-18), N-acetyl-glucosaminidase (NAG),
      glutathione transferases (GST) and liver fatty acid binding protein (LFABP)] to
      identify relevant papers in five different settings (paediatrics, cardiac
      surgery, emergency department, critically ill and contrast-induced nephropathy).
      RESULTS: We included 87 relevant papers, reporting on 74 studies. Depending upon
      the setting, 7-27 different definitions of AKI were used. Reported diagnostic
      performance of the different biomarkers was variable from poor to excellent, and
      no consistent generalizable conclusions can be drawn on their diagnostic value.
      CONCLUSIONS: Early diagnosing of AKI in clinical conditions by using new serum
      and urinary biomarkers remains cumbersome, especially in those settings where
      timing and aetiology of AKI are not well defined. Putting too much emphasis on
      markers that have not convincingly proven reliability might lead to incorrect
      interpretation of clinical trials. Further research in this field is warranted
      before biomarkers can be introduced in clinical practice.

PMID- 23115327
TI  - Unhealthy drinking in the Belgian elderly population: prevalence and associated
      characteristics.
AB  - BACKGROUND: Knowledge about alcohol consumption patterns and alcohol problems
      among the Belgian elderly population is scarce. The aims of this study were to
      explore alcohol consumption patterns and alcohol problems among the Belgian
      elderly population aged >= 65 years living at home, and to determine their
      association with socio-demographic characteristics, health status and socio
      economic status. METHODS: In this cross-sectional study based on a representative
      sample of 4825 non-institutionalized Belgian elderly people (>= 65 years) in the
      Belgian Health Interview Surveys 2001 and 2004, alcohol consumption patterns and
      alcohol problems were estimated according to age, gender, survey year, living
      situation, frequency of social contacts, smoking status, and socio-economic
      status. RESULTS: In all, 50.4% of the sample were non- or occasional drinkers,
      29.1% were moderate drinkers, 10.4% at-risk drinkers, 4.6% heavy drinkers and
      5.5% problematic drinkers. In total, 20.5% of the Belgian elderly population
      drank in excess of the National Institute on Alcohol Abuse and Alcoholism
      guidelines, and 4.7% had an alcohol problem according to the CAGE. In addition,
      81.3% of the elderly people who consume alcohol used prescribed medications in
      the past 2 weeks. After adjustment for risk factors we found that, compared with
      moderate drinking, unhealthy drinking was significantly associated with age,
      gender, frequency of social contacts, health status and socio-economic status.
      CONCLUSIONS: Belgian health policy should be aware of the high level of at-risk
      drinkers in the elderly population and the underdetection and misdiagnosis of
      alcohol problems in this age group. An increased attention in public health
      initiatives among the Belgian elderly population is needed.

PMID- 23115328
TI  - Prevalence and determinants of tobacco use among adults in Greece: 4 year trends.
AB  - BACKGROUND: Greece has one of the highest rates of adult smoking globally. The
      objective of the present survey was to explore the epidemiology of tobacco use in
      Greece after the implementation of recent legislative tobacco control measures
      and to compare it with previous cross-sectional data from 2006. METHODS: The
      nationwide household survey 'Hellas Health III' was conducted in 2010. A sample
      of 1000 adults (mean age 47.1 +/- 17.1 years) were interviewed. Individuals who
      had smoked at least once during the past 30 days were classified as smokers.
      Results were compared with those from the similar 'Hellas Health I' study, which
      was conducted in 2006. RESULTS: The prevalence of smoking was calculated at 41%
      (45% among men and 38% in women, P = 0.04). Greek men smoke more cigarettes (23.2
      vs. 19.3 per day, P = 0.002), and they become regular smokers earlier in life. In
      age groups <55 years, most gender inequalities are attenuated. Socio-economic
      status does not affect tobacco use in Greece. In comparison with 2006, smoking
      prevalence, especially among young adults, has fallen from 48 to 35% in 2010.
      Moreover, a substantial reduction in the number of cigarettes smoked among all
      age groups was noticed. CONCLUSIONS: Trends in smoking prevalence and consumption
      among adults seem favourable in Greece during the past 4 years; a substantial
      reduction of younger smokers and in the number of cigarettes smoked among all age
      groups is documented. This constitutes a significant public health achievement
      and an indicator that young adults are a susceptible population to legislative
      action.

PMID- 23115329
TI  - Adherence to physical exercise recommendations in people over 65--the SNAC
      Kungsholmen study.
AB  - BACKGROUND: There is limited knowledge regarding to what extent the older
      population meet the recommendations of physical exercise, especially fitness
      enhancing exercise. This study assessed participation in health- and fitness
      enhancing exercises in people aged >65, and explored to what extent the possible
      differences in meeting current recommendations differs by age, gender and
      education. METHODS: The study population was derived from the Swedish National
      study on Aging and Care, and consisted of a random sample of 2593 subjects, aged
      65+ years. Participation in health- and fitness-enhancing exercise according to
      the WHO and the American College of Sports Medicine's recommendations in relation
      to age, gender and education was evaluated using multinomial logistic regression
      adjusted for health indicators and physical performance. RESULTS: According to
      the recommendations, 46% of the participants fulfilled the criteria for health
      enhancing and 16% for fitness-enhancing exercises. Independent of health
      indicators and physical performance, women <80 years of age were less likely than
      men to participate in fitness-enhancing exercise, but they participated more in
      health-enhancing exercise. In the advanced age group (80+ years), women were less
      likely to participate both in fitness- and health-enhancing exercise. Advanced
      age and low education were negatively related to participation in both health-
      and fitness-enhancing exercise independent of health indicators, but the
      association was not observed among people with fast walking speed. CONCLUSION:
      Promoting physical exercise and encouraging participation among older adults with
      lower education, especially among those with initial functional decline, may help
      to reduce adverse health outcomes.

PMID- 23115330
TI  - Predicting rates of cell state change caused by stochastic fluctuations using a
      data-driven landscape model.
AB  - We develop a potential landscape approach to quantitatively describe experimental
      data from a fibroblast cell line that exhibits a wide range of GFP expression
      levels under the control of the promoter for tenascin-C. Time-lapse live-cell
      microscopy provides data about short-term fluctuations in promoter activity, and
      flow cytometry measurements provide data about the long-term kinetics, because
      isolated subpopulations of cells relax from a relatively narrow distribution of
      GFP expression back to the original broad distribution of responses. The
      landscape is obtained from the steady state distribution of GFP expression and
      connected to a potential-like function using a stochastic differential equation
      description (Langevin/Fokker-Planck). The range of cell states is constrained by
      a force that is proportional to the gradient of the potential, and biochemical
      noise causes movement of cells within the landscape. Analyzing the mean square
      displacement of GFP intensity changes in live cells indicates that these
      fluctuations are described by a single diffusion constant in log GFP space. This
      finding allows application of the Kramers' model to calculate rates of switching
      between two attractor states and enables an accurate simulation of the dynamics
      of relaxation back to the steady state with no adjustable parameters. With this
      approach, it is possible to use the steady state distribution of phenotypes and a
      quantitative description of the short-term fluctuations in individual cells to
      accurately predict the rates at which different phenotypes will arise from an
      isolated subpopulation of cells.

PMID- 23115331
TI  - Gain-of-function Nav1.8 mutations in painful neuropathy.
AB  - Painful peripheral neuropathy often occurs without apparent underlying cause.
      Gain-of-function variants of sodium channel Na(v)1.7 have recently been found in
      ~30% of cases of idiopathic painful small-fiber neuropathy. Here, we describe
      mutations in Na(v)1.8, another sodium channel that is specifically expressed in
      dorsal root ganglion (DRG) neurons and peripheral nerve axons, in patients with
      painful neuropathy. Seven Na(v)1.8 mutations were identified in 9 subjects within
      a series of 104 patients with painful predominantly small-fiber neuropathy. Three
      mutations met criteria for potential pathogenicity based on predictive algorithms
      and were assessed by voltage and current clamp. Functional profiling showed that
      two of these three Na(v)1.8 mutations enhance the channel's response to
      depolarization and produce hyperexcitability in DRG neurons. These observations
      suggest that mutations of Na(v)1.8 contribute to painful peripheral neuropathy.

PMID- 23115332
TI  - High-pressure study of lithium amidoborane using Raman spectroscopy and insight
      into dihydrogen bonding absence.
AB  - One of the major obstacles to the use of hydrogen as an energy carrier is the
      lack of proper hydrogen storage material. Lithium amidoborane has attracted
      significant attention as hydrogen storage material. It releases ~10.9 wt%
      hydrogen, which is beyond the Department of Energy target, at remarkably low
      temperature (~90  degrees C) without borazine emission. It is essential to study
      the bonding behavior of this potential material to improve its dehydrogenation
      behavior further and also to make rehydrogenation possible. We have studied the
      high-pressure behavior of lithium amidoborane in a diamond anvil cell using in
      situ Raman spectroscopy. We have discovered that there is no dihydrogen bonding
      in this material, as the N-H stretching modes do not show redshift with pressure.
      The absence of the dihydrogen bonding in this material is an interesting
      phenomenon, as the dihydrogen bonding is the dominant bonding feature in its
      parent compound ammonia borane. This observation may provide guidance to the
      improvement of the hydrogen storage properties of this potential material and to
      design new material for hydrogen storage application. Also two phase transitions
      were found at high pressure at 3.9 and 12.7 GPa, which are characterized by
      sequential changes of Raman modes.

PMID- 23115333
TI  - Optical spectroscopy shows that the normal state of URu2Si2 is an anomalous Fermi
      liquid.
AB  - Fermi showed that, as a result of their quantum nature, electrons form a gas of
      particles whose temperature and density follow the so-called Fermi distribution.
      As shown by Landau, in a metal the electrons continue to act like free quantum
      mechanical particles with enhanced masses, despite their strong Coulomb
      interaction with each other and the positive background ions. This state of
      matter, the Landau-Fermi liquid, is recognized experimentally by an electrical
      resistivity that is proportional to the square of the absolute temperature plus a
      term proportional to the square of the frequency of the applied field.
      Calculations show that, if electron-electron scattering dominates the resistivity
      in a Landau-Fermi liquid, the ratio of the two terms, b, has the universal value
      of b = 4. We find that in the normal state of the heavy Fermion metal
      URu(2)Si(2), instead of the Fermi liquid value of 4, the coefficient b = 1 +/-
      0.1. This unexpected result implies that the electrons in this material are
      experiencing a unique scattering process. This scattering is intrinsic and we
      suggest that the uranium f electrons do not hybridize to form a coherent Fermi
      liquid but instead act like a dense array of elastic impurities, interacting
      incoherently with the charge carriers. This behavior is not restricted to
      URu(2)Si(2). Fermi liquid-like states with b ? 4 have been observed in a number
      of disparate systems, but the significance of this result has not been
      recognized.

PMID- 23115334
TI  - Hornwort pyrenoids, carbon-concentrating structures, evolved and were lost at
      least five times during the last 100 million years.
AB  - Ribulose-1,5-biphosphate-carboxylase-oxygenase (RuBisCO) has a crucial role in
      carbon fixation but a slow catalytic rate, a problem overcome in some plant
      lineages by physiological and anatomical traits that elevate carbon
      concentrations around the enzyme. Such carbon-concentrating mechanisms are
      hypothesized to have evolved during periods of low atmospheric CO(2). Hornworts,
      the sister to vascular plants, have a carbon-concentrating mechanism that relies
      on pyrenoids, proteinaceous bodies mostly consisting of RuBisCO. We generated a
      phylogeny based on mitochondrial and plastid sequences for 36% of the
      approximately 200 hornwort species to infer the history of gains and losses of
      pyrenoids in this clade; we also used fossils and multiple dating approaches to
      generate a chronogram for the hornworts. The results imply five to six origins
      and an equal number of subsequent losses of pyrenoids in hornworts, with the
      oldest pyrenoid gained ca. 100 Mya, and most others at <35 Mya. The
      nonsynchronous appearance of pyrenoid-containing clades, the successful
      diversification of pyrenoid-lacking clades during periods with low [CO(2)], and
      the maintenance of pyrenoids during episodes of high [CO(2)] all argue against
      the previously proposed relationship between pyrenoid origin and low [CO(2)]. The
      selective advantages, and costs, of hornwort pyrenoids thus must relate to
      additional factors besides atmospheric CO(2).

PMID- 23115335
TI  - TFIIB dephosphorylation links transcription inhibition with the p53-dependent DNA
      damage response.
AB  - The general transcription factor II B (TFIIB) plays a central role in both the
      assembly of the transcription complex at gene promoters and also in the events
      that lead to transcription initiation. TFIIB is phosphorylated at serine-65 at
      the promoters of several endogenous genes, and this modification is required to
      drive the formation of gene promoter-3' processing site contacts through the
      cleavage stimulation factor 3' (CstF 3')-processing complex. Here we demonstrate
      that TFIIB phosphorylation is dispensable for the transcription of genes
      activated by the p53 tumor suppressor. We find that the kinase activity of TFIIH
      is critical for the phosphorylation of TFIIB serine-65, but it is also
      dispensable for the transcriptional activation of p53-target genes. Moreover, we
      demonstrate that p53 directly interacts with CstF independent of TFIIB
      phosphorylation, providing an alternative route to the recruitment of 3'
      processing complexes to the gene promoter. Finally, we show that DNA damage leads
      to a reduction in the level of phospho-ser65 TFIIB that leaves the p53
      transcriptional response intact, but attenuates transcription at other genes. Our
      data reveal a mode of phospho-TFIIB-independent transcriptional regulation that
      prioritizes the transcription of p53-target genes during cellular stress.

PMID- 23115336
TI  - Cartilage tissue engineering using differentiated and purified induced
      pluripotent stem cells.
AB  - The development of regenerative therapies for cartilage injury has been greatly
      aided by recent advances in stem cell biology. Induced pluripotent stem cells
      (iPSCs) have the potential to provide an abundant cell source for tissue
      engineering, as well as generating patient-matched in vitro models to study
      genetic and environmental factors in cartilage repair and osteoarthritis.
      However, both cell therapy and modeling approaches require a purified and
      uniformly differentiated cell population to predictably recapitulate the
      physiological characteristics of cartilage. Here, iPSCs derived from adult mouse
      fibroblasts were chondrogenically differentiated and purified by type II collagen
      (Col2)-driven green fluorescent protein (GFP) expression. Col2 and aggrecan gene
      expression levels were significantly up-regulated in GFP+ cells compared with GFP
      cells and decreased with monolayer expansion. An in vitro cartilage defect model
      was used to demonstrate integrative repair by GFP+ cells seeded in agarose,
      supporting their potential use in cartilage therapies. In chondrogenic pellet
      culture, cells synthesized cartilage-specific matrix as indicated by high levels
      of glycosaminoglycans and type II collagen and low levels of type I and type X
      collagen. The feasibility of cell expansion after initial differentiation was
      illustrated by homogenous matrix deposition in pellets from twice-passaged GFP+
      cells. Finally, atomic force microscopy analysis showed increased microscale
      elastic moduli associated with collagen alignment at the periphery of pellets,
      mimicking zonal variation in native cartilage. This study demonstrates the
      potential use of iPSCs for cartilage defect repair and for creating tissue models
      of cartilage that can be matched to specific genetic backgrounds.

PMID- 23115337
TI  - Preseismic anomalous telluric current signals observed in Kozu-shima Island,
      Japan.
AB  - Monitoring of telluric current, which is practically a synonym for geoelectric
      potential difference, was conducted on Kozu-shima Island about 170 km south of
      Tokyo from May 14, 1997 to June 25, 2000. During the monitoring period, 19
      anomalous telluric current changes (ATCs) were observed. Their possible
      correlation with nearby earthquakes was statistically examined by assuming
      various lead times for different ranges of magnitude and focal distance. The best
      correlation may be obtained for earthquakes with a magnitude greater than 3.0
      occurring within 20 km of focal distance. There were 23 such earthquakes, of
      which 11 were preceded by ATCs within 30 d. Of these 11 earthquakes, preceding
      ATCs of 5 and 6 were positive and negative polarities of telluric current,
      respectively. Their epicenters were spatially well clustered in the east and west
      of the island. These facts were clearly beyond those expected by chance and led
      to a simple speculative model.

PMID- 23115338
TI  - Evolutionary layering and the limits to cellular perfection.
AB  - Although observations from biochemistry and cell biology seemingly illustrate
      hundreds of examples of exquisite molecular adaptations, the fact that
      experimental manipulation can often result in improvements in cellular
      infrastructure raises the question as to what ultimately limits the level of
      molecular perfection achievable by natural selection. Here, it is argued that
      random genetic drift can impose a strong barrier to the advancement of molecular
      refinements by adaptive processes. Moreover, although substantial improvements in
      fitness may sometimes be accomplished via the emergence of novel cellular
      features that improve on previously established mechanisms, such advances are
      expected to often be transient, with overall fitness eventually returning to the
      level before incorporation of the genetic novelty. As a consequence of such
      changes, increased molecular/cellular complexity can arise by Darwinian
      processes, while yielding no long-term increase in adaptation and imposing
      increased energetic and mutational costs.

PMID- 23115339
TI  - Complex-type N-glycan recognition by potent broadly neutralizing HIV antibodies.
AB  - Broadly neutralizing HIV antibodies (bNAbs) can recognize carbohydrate-dependent
      epitopes on gp120. In contrast to previously characterized glycan-dependent bNAbs
      that recognize high-mannose N-glycans, PGT121 binds complex-type N-glycans in
      glycan microarrays. We isolated the B-cell clone encoding PGT121, which
      segregates into PGT121-like and 10-1074-like groups distinguished by sequence,
      binding affinity, carbohydrate recognition, and neutralizing activity. Group 10
      1074 exhibits remarkable potency and breadth but no detectable binding to protein
      free glycans. Crystal structures of unliganded PGT121, 10-1074, and their likely
      germ-line precursor reveal that differential carbohydrate recognition maps to a
      cleft between complementarity determining region (CDR)H2 and CDRH3. This cleft
      was occupied by a complex-type N-glycan in a "liganded" PGT121 structure.
      Swapping glycan contact residues between PGT121 and 10-1074 confirmed their
      importance for neutralization. Although PGT121 binds complex-type N-glycans,
      PGT121 recognized high-mannose-only HIV envelopes in isolation and on virions. As
      HIV envelopes exhibit varying proportions of high-mannose- and complex-type N
      glycans, these results suggest promiscuous carbohydrate interactions, an
      advantageous adaptation ensuring neutralization of all viruses within a given
      strain.

PMID- 23115341
TI  - The effect of an apparent change to a branded or generic medication on drug
      effectiveness and side effects.
AB  - OBJECTIVE: Generic medications are associated with reduced perceived
      effectiveness, increased perceived adverse effects, and increased rates of
      nonadherence compared with brand-name medications. This study examined the effect
      of an apparent medication formulation change on subjective and objective measures
      of medication effectiveness and medication side effects. METHODS: Sixty-two
      university students participated in a study purportedly testing the effectiveness
      of fast-acting beta-blocker medications in reducing preexamination anxiety. All
      tablets were placebos. In session 1, all participants received a yellow tablet
      ("Betaprol"). In session 2, participants were randomly allocated to receive
      Betaprol (no change condition) or a white tablet labeled either as "Novaprol"
      (branded change condition) or "Generic" (generic change condition). Blood
      pressure and state anxiety were measured before and after tablet ingestion. Side
      effects attributed to medication were assessed. RESULTS: The no change group
      showed significantly greater decreases in systolic blood pressure (mean [M]
      [standard deviation] = -7.72 mm Hg, standard error [SE] = 1.45) than the branded
      change (M = -2.75 mm Hg, SE = 1.44, p = .02) and generic change (M = -3.26 mm Hg,
      SE = 1.45, p = .03) groups. The no-change group showed significantly greater
      decreases in state anxiety (M = -1.53, SE = 0.33) than the branded change (M = 
      0.50, SE = 0.33, p = .03) and generic change (M = -0.52, SE = 0.33, p = .04)
      groups. Significantly more side effects were attributed to the medication in the
      generic change (M = 1.83, SE = 0.23) (but not the branded change) condition when
      compared with the no change condition (M = 0.87, SE = 0.31, p = .03).
      CONCLUSIONS: Medication formulation change, particularly to generic medication,
      seems to be associated with reduced subjective and objective measures of
      medication effectiveness and increased side effects.

PMID- 23115342
TI  - Neural dysregulation in posttraumatic stress disorder: evidence for disrupted
      equilibrium between salience and default mode brain networks.
AB  - OBJECTIVE: Convergent research demonstrates disrupted attention and heightened
      threat sensitivity in posttraumatic stress disorder (PTSD). This might be linked
      to aberrations in large-scale networks subserving the detection of salient
      stimuli (i.e., the salience network [SN]) and stimulus-independent, internally
      focused thought (i.e., the default mode network [DMN]). METHODS: Resting-state
      brain activity was measured in returning veterans with and without PTSD (n = 15
      in each group) and in healthy community controls (n = 15). Correlation
      coefficients were calculated between the time course of seed regions in key SN
      and DMN regions and all other voxels of the brain. RESULTS: Compared with control
      groups, participants with PTSD showed reduced functional connectivity within the
      DMN (between DMN seeds and other DMN regions) including the rostral anterior
      cingulate cortex/ventromedial prefrontal cortex (z = 3.31; p = .005, corrected)
      and increased connectivity within the SN (between insula seeds and other SN
      regions) including the amygdala (z = 3.03; p = .01, corrected). Participants with
      PTSD also demonstrated increased cross-network connectivity. DMN seeds exhibited
      elevated connectivity with SN regions including the insula (z = 3.06; p = .03,
      corrected), and SN seeds exhibited elevated connectivity with DMN regions
      including the hippocampus (z = 3.10; p = .048, corrected). CONCLUSIONS: During
      resting-state scanning, participants with PTSD showed reduced coupling within the
      DMN, greater coupling within the SN, and increased coupling between the DMN and
      the SN. Our findings suggest a relative dominance of threat-sensitive circuitry
      in PTSD, even in task-free conditions. Disequilibrium between large-scale
      networks subserving salience detection versus internally focused thought may be
      associated with PTSD pathophysiology.

PMID- 23115343
TI  - Peak-end memory bias in laboratory-induced dyspnea: a comparison of patients with
      medically unexplained symptoms and healthy controls.
AB  - OBJECTIVE: Memory for unpleasant experiences is dominated by intensity at the
      experience's peak and end, with a relative neglect for its duration. Therefore,
      unpleasant somatic experiences are expected be remembered as less aversive when
      they end gradually rather than abruptly, even when they last longer (i.e., the
      "peak-end effect"). We investigated the peak-end effect for dyspnea in healthy
      participants and in patients with medically unexplained dyspnea (MUD). METHODS:
      Two aversive dyspnea-inducing tasks were administered to a clinical MUD sample (n
      = 29) and a matched healthy control group (n = 29) using a rebreathing paradigm
      (60-second room air, 150-second rebreathing). In a short trial, the breathing
      system (mouthpiece) was removed immediately after peak dyspnea. In a long trial,
      breathing was switched to room air after peak dyspnea and continued in the
      breathing system for 150 seconds (order was counterbalanced across participants).
      Respiratory parameters were continuously measured, and dyspnea was rated every 10
      seconds. Relative unpleasantness of the dyspneic episode was assessed with forced
      choice questions. RESULTS: More than 70% of the healthy group found the short
      episode worse than the long one despite equal maximal dyspnea (p = .02). Patients
      with MUD did not show this peak-end effect (p = .58). The latter had deficient
      recovery of dyspnea compared with the controls (42.08 [21.86] versus 17.51
      [11.18], p < .001), which could not be explained by differences in respiratory
      physiology. CONCLUSIONS: The peak-end effect in dyspnea has important
      implications for dyspnea measurement. Its absence in patients with MUD suggests a
      critical role of distorted perceptual-cognitive processing of aversive somatic
      sensations in patients with medically unexplained symptoms.

PMID- 23115345
TI  - The temporal relation between pain and depression: results from the longitudinal
      aging study Amsterdam.
AB  - OBJECTIVE: Pain and depression are both common in old age, but their (long-term)
      temporal relationship remains unknown. This study is designed to determine
      whether pain predicts the onset of depression and vice versa. METHODS: This is a
      prospective, population-based cohort study with 12-year follow-up and 3-year
      intervals in the Netherlands (Longitudinal Aging Study Amsterdam). At baseline,
      participants were aged 55 to 85 years (n = 2028). Main measurements outcomes were
      incident depression defined as crossing the cutoff of 16 and showing a relevant
      change (>= 5 points) on the Center for Epidemiological Studies-Depression Scale
      among nondepressed participants and incident pain defined as a score of 2 or
      higher on the pain scale of the 5-item Nottingham Health Profile in pain-free
      participants. Multiple imputations were adopted to estimate missing values.
      RESULTS: In nondepressed participants (n = 1769), a higher level of pain was
      predictive of incident depression in multiple extended Cox regression analyses
      (hazard rate [HR] = 1.13 [95% confidence interval {CI}: 1.05-1.22], p = .001),
      which all remained significant after correction for sociodemographic
      characteristics, life-style characteristics, functional limitations, and chronic
      diseases (HR = 1.09 [95% CI = 1.01-1.18], p = .035). In the pain-free
      participants (n = 1420), depressive symptoms at baseline predicted incident pain
      (HR = 1.02 [95% CI: 1.01-1.04], p = .006). This depression measure did not
      independently predicted the onset of pain in the fully adjusted models.
      CONCLUSIONS: As pain precedes the onset of depression, strategies to prevent
      depression in chronic pain patients are warranted. In contrast, no effects of
      depression on the development of subsequent pain were found when adjusting for
      covariates.

PMID- 23115344
TI  - Cognitive function and treatment adherence in older adults with heart failure.
AB  - OBJECTIVE: Treatment recommendation and guidelines for patients with heart
      failure (HF) can be complex, and past work has shown that patients with HF
      demonstrate low rates of adherence to recommended health behaviors. Although
      previous work has identified several medical, demographic, and psychosocial
      predictors of the capacity to adhere to treatment recommendations of persons with
      HF, little is known about the contribution of cognitive impairment to reported
      treatment adherence in this population. METHODS: A total of 149 persons with HF
      (mean [standard deviation] = 68.08 [10.74] years) completed a brief fitness
      assessment and neuropsychological testing. Treatment adherence was assessed using
      the Heart Failure Compliance Questionnaire, a brief measure that asks
      participants to report their adherence to a variety of recommended health
      behaviors (i.e., medication management, diet, and exercise, among others).
      RESULTS: The percentage of participants who reported poor overall adherence was
      16.1%, with particularly high rates of nonadherence to dietary and exercise
      recommendations. Hierarchical regression analyses adjusting for possible
      confounds revealed that reduced performance on attention (beta = .26, p = .01),
      executive function (beta = .18, p = .04), and language (beta = .22, p = .01) was
      associated with poorer overall adherence. Follow-up analyses showed that these
      cognitive domains were associated with behaviors such as keeping doctor
      appointments, medication management, and dietary recommendations (p < .05 for
      all). CONCLUSIONS: The current findings demonstrate that cognitive function is an
      independent contributor to adherence in older adults with HF. Prospective studies
      that objectively measure treatment adherence are needed to clarify these findings
      and identify possible strategies to improve outcomes in this population. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00871897.

PMID- 23115346
TI  - Associations between health-related self-protection, diurnal cortisol, and C
      reactive protein in lonely older adults.
AB  - OBJECTIVES: The aim of this study was to examine whether health-related self
      protection (e.g., using positive reappraisals or avoiding self-blame) prevents
      lonely older adults from exhibiting increases in diurnal cortisol secretion and
      higher levels of C-reactive protein (CRP). METHODS: This longitudinal study (n =
      122) examined diurnal cortisol levels (area under the curve) at baseline and 2
      year follow-up. Levels of CRP were measured at 6-year follow-up. The main
      predictors included baseline levels of loneliness and health-related self
      protection. RESULTS: Among lonely participants, baseline self-protection
      predicted an amelioration of 2-year increases in diurnal cortisol volume (beta = 
      .34, p = .03) and lower levels of CRP at 6-year follow-up (beta = -.42, p =
      .006). These significant associations were not found among nonlonely participants
      (beta < .14, p = .33). In addition, mediation analyses demonstrated that the
      buffering effect of self-protection on lonely older adults' levels of CRP at 6
      year follow-up was statistically mediated by 2-year changes in cortisol volume
      (beta = -.16, p = .06). CONCLUSIONS: These findings suggest that lonely older
      adults may ameliorate biologic disturbances if they engage in self-protection to
      cope with their health threats.

PMID- 23115347
TI  - Grapheme-color synesthesia and posttraumatic stress disorder: preliminary results
      from the veterans health study.
AB  - OBJECTIVE: Posttraumatic stress disorder (PTSD) is associated with altered
      neuropsychological function, possibly including complex visual information
      processing. Grapheme-color synesthesia refers to the phenomenon that a particular
      letter or number elicits the visual perception of a specific color. The study
      objective was to assess if grapheme-color synesthesia was associated with PTSD
      among US veterans. METHOD: We surveyed 700 veterans who were outpatients in a
      multihospital system in Pennsylvania. All veterans had served at least one
      warzone deployment. PTSD and grapheme-color synesthesia were assessed using
      validated research instruments. RESULTS: The mean age of veterans was 59 years,
      and 96% were men. The prevalence of current PTSD was 7% (95% confidence interval
      [CI] = 5.1-8.8), and current partial PTSD was 11% (95% CI = 9.3-14.0). The
      prevalence of current depression was 6% (95% CI = 4.7-8.3). Altogether, 6% (95%
      CI = 4.8-8.5) of veterans screened positive for grapheme-color synesthesia.
      Bivariate analyses suggested that grapheme-color synesthesia was associated with
      current PTSD (odds ratio [OR] = 3.4, p = .004) and current partial PTSD (OR =
      2.4, p = .013), but not current depression (OR = 1.1, p = .91). Multivariate
      logistic regression results, adjusting for age, sex, marital status, level of
      education, current psychotropic medication use, and concussion history, confirmed
      these results. CONCLUSIONS: Grapheme-color synesthesia seems to be associated
      with PTSD among veterans who had been deployed. This finding may have
      implications for PTSD diagnostic screening and treatment. Research is recommended
      to confirm this finding and to determine if synesthesia is a risk indicator for
      PTSD among nonveterans.

PMID- 23115348
TI  - Polarised bovine endometrial epithelial cells vectorially secrete prostaglandins
      and chemotactic factors under physiological and pathological conditions.
AB  - Epithelial cells of the endometrium secrete prostaglandins to regulate the bovine
      oestrous cycle and form a functional barrier to microbes. However, bacterial
      infection of the endometrium commonly causes infertility in dairy cattle by
      disrupting endometrial physiology. Epithelial cell cultures are used to study the
      mechanisms of physiology and pathology, but 2D cultures may not reflect the 3D
      complexity of the epithelium. In this study, a polarised epithelial cell
      transwell culture was developed, using transepithelial resistance (TER), to
      monitor epithelial integrity. Polarised epithelial cells were treated with
      oxytocin and arachidonic acid to test physiological function and with
      lipopolysaccharide (LPS) to mimic bacterial infection. Supernatants were analysed
      for prostaglandin E(2) (PGE), prostaglandin F(2)(alpha), the chemokine
      interleukin-8 (IL8) and the ability of supernatants to induce neutrophil
      migration. Confluent epithelial cells established polarity when TER was >1800 
      Omega cm(2) and predominantly released prostaglandins basolaterally. In contrast,
      IL8 from epithelial cells accumulated apically and the supernatants were highly
      chemotactic for neutrophils. The striking exception was when the epithelial cells
      were treated with LPS in the apical or basolateral compartment independently,
      which led to the release of IL8 towards the treated compartment. Although stromal
      cells also accumulated PGE and IL8 in response to treatment, co-culture of
      stromal cells in the well below polarised epithelial cells did not influence
      cellular responses. In conclusion, polarised endometrial epithelial cells
      vectorially released prostaglandins and chemokines to reflect their respective
      mechanistic roles in physiology and pathology.

PMID- 23115349
TI  - Changing expression of chloride channels during preimplantation mouse
      development.
AB  - Plasma membrane chloride channels (ClCs) play important roles in a broad range of
      cellular processes including cell volume regulation, proliferation, and
      transepithelial transport, all of which are critical during preimplantation
      embryonic development. In this study, the molecular and functional expression of
      voltage-gated ClCs was analyzed throughout preimplantation development of the
      mouse conceptus. mRNA transcripts for all Clcn genes were detected. Only Clcn1
      mRNA showed differential expression in the blastocyst, being detected in the
      trophectoderm but not in the inner cell mass. CLCN3 protein was detected at low
      levels in the cytoplasm and plasma membrane in 4-cell embryos and was localized
      to the apical plasma membrane of the trophoblasts in the blastocyst. Whole-cell
      patch-clamp recordings demonstrated the presence of a DIDS-sensitive, outwardly
      rectifying Cl(-) current throughout development, with this conductance being
      large at the 1-cell, morula and blastocyst stages. A second DIDS-insensitive Cl(
      ) current, which was inactivated by membrane depolarization, was present in cells
      differentiating into the trophoblast lineage and during blastocyst expansion.
      Inhibition of the DIDS-sensitive current and the DIDS-insensitive current, with 9
      AC, prevented blastocyst expansion.

PMID- 23115351
TI  - Emerging economies, enduring partnerships.

PMID- 23115350
TI  - Effects of mechanical stimulation on viscoelasticity of rabbit scleral
      fibroblasts after posterior scleral reinforcement.
AB  - To understand the effect of mechanical stimulation on posterior scleral
      reinforcement (PSR), rabbit scleral fibroblasts after PSR were subjected to
      stretch in vitro, and the viscoelastic behavior of scleral fibroblasts was
      evaluated. Three-week-old rabbits were monocularly treated by eyelid suturation
      randomly to prepare the experimental myopia eyes. After 60 days, the experimental
      myopia eyes were treated by PSR. After six months, the posterior pole scleral
      fibroblasts (normal sclera--group A, sclera after operation--B and fusion region
      of sclera and reinforcing band - group C) were isolated and cultured in vitro.
      The cells were subjected to cyclic stretch regimens (sine wave, 3% and 6%
      elongation amplitude, 0.1 Hz, 48-h duration) by an FX-4000 Tension System. The
      micropipette aspiration technique was used to investigate the viscoelasticity of
      scleral fibroblasts. The cellular viscoelasticity (E(0), E(infinity) and MU) of
      group C was significantly lower than groups A and B (P < 0.05), and there was no
      significant difference between groups A and B (P > 0.05). The results show that
      the viscoelasticity in different regions of sclera after PSR is different.
      Following a 48-h stretch, the cellular viscoelastic parameters were significantly
      decreased when compared with the respective static groups (P < 0.05) in groups A
      and B. For group C, the viscoelasticity of the stretch group was significantly
      higher than the static control group (P < 0.05). There was no difference between
      the 3% and 6% stretch groups in each group (P > 0.05). The changes of
      viscoelasticity suggest that different regions of sclera have different responses
      to mechanical stimulation in the process of treating high myopia by PSR and that
      mechanical stimulation plays an important role in the treatment of axial myopia
      by regulating the viscoelasticity of scleral fibroblasts.

PMID- 23115352
TI  - A window into metastasis.
AB  - A new glass window construction by Ritsma, Steller et al. allows chronic, high
      resolution imaging of cancer metastasis in the mouse abdomen.

PMID- 23115353
TI  - Food-grade bacteria expressing elafin protect against inflammation and restore
      colon homeostasis.
AB  - Elafin, a natural protease inhibitor expressed in healthy intestinal mucosa, has
      pleiotropic anti-inflammatory properties in vitro and in animal models. We found
      that mucosal expression of Elafin is diminished in patients with inflammatory
      bowel disease (IBD). This defect is associated with increased elastolytic
      activity (elastase-like proteolysis) in colon tissue. We engineered two food
      grade strains of lactic acid bacteria (LAB) to express and deliver Elafin to the
      site of inflammation in the colon to assess the potential therapeutic benefits of
      the Elafin-expressing LAB. In mouse models of acute and chronic colitis, oral
      administration of Elafin-expressing LAB decreased elastolytic activity and
      inflammation and restored intestinal homeostasis. Furthermore, when cultures of
      human intestinal epithelial cells were treated with LAB secreting Elafin, the
      inflamed epithelium was protected from increased intestinal permeability and from
      the release of cytokines and chemokines, both of which are characteristic of
      intestinal dysfunction associated with IBD. Together, these results suggest that
      oral delivery of LAB secreting Elafin may be useful for treating IBD in humans.

PMID- 23115354
TI  - Intravital microscopy through an abdominal imaging window reveals a pre
      micrometastasis stage during liver metastasis.
AB  - Cell dynamics in subcutaneous and breast tumors can be studied through
      conventional imaging windows with intravital microscopy. By contrast,
      visualization of the formation of metastasis has been hampered by the lack of
      long-term imaging windows for metastasis-prone organs, such as the liver. We
      developed an abdominal imaging window (AIW) to visualize distinct biological
      processes in the spleen, kidney, small intestine, pancreas, and liver. The AIW
      can be used to visualize processes for up to 1 month, as we demonstrate with
      islet cell transplantation. Furthermore, we have used the AIW to image the single
      steps of metastasis formation in the liver over the course of 14 days. We
      observed that single extravasated tumor cells proliferated to form "pre
      micrometastases," in which cells lacked contact with neighboring tumor cells and
      were active and motile within the confined region of the growing clone. The
      clones then condensed into micrometastases where cell migration was strongly
      diminished but proliferation continued. Moreover, the metastatic load was reduced
      by suppressing tumor cell migration in the pre-micrometastases. We suggest that
      tumor cell migration within pre-micrometastases is a contributing step that can
      be targeted therapeutically during liver metastasis formation.

PMID- 23115355
TI  - Immune parameters correlate with protection against ebola virus infection in
      rodents and nonhuman primates.
AB  - Ebola virus causes severe hemorrhagic fever in susceptible hosts. Currently, no
      licensed vaccines or treatments are available; however, several experimental
      vaccines have been successful in protecting rodents and nonhuman primates (NHPs)
      from the lethal Zaire ebolavirus (ZEBOV) infection. The objective of this study
      was to evaluate immune responses correlating with survival in these animals after
      lethal challenge with ZEBOV. Knockout mice with impaired ability to generate
      normal T and/or B cell responses were vaccinated and challenged with ZEBOV.
      Vaccine-induced protection in mice was mainly mediated by B cells and CD4(+) T
      cells. Vaccinated, outbred guinea pigs and NHPs demonstrated the highest
      correlation between survival and levels of total immunoglobulin G (IgG) specific
      to the ZEBOV glycoprotein (ZGP). These results highlight the relevance of total
      ZGP-specific IgG levels as a meaningful correlate of protection against ZEBOV
      exposure.

PMID- 23115357
TI  - Racehorse abuse - a comment.

PMID- 23115356
TI  - Computational medicine: translating models to clinical care.
AB  - Because of the inherent complexity of coupled nonlinear biological systems, the
      development of computational models is necessary for achieving a quantitative
      understanding of their structure and function in health and disease. Statistical
      learning is applied to high-dimensional biomolecular data to create models that
      describe relationships between molecules and networks. Multiscale modeling links
      networks to cells, organs, and organ systems. Computational approaches are used
      to characterize anatomic shape and its variations in health and disease. In each
      case, the purposes of modeling are to capture all that we know about disease and
      to develop improved therapies tailored to the needs of individuals. We discuss
      advances in computational medicine, with specific examples in the fields of
      cancer, diabetes, cardiology, and neurology. Advances in translating these
      computational methods to the clinic are described, as well as challenges in
      applying models for improving patient health.

PMID- 23115359
TI  - Veterinary medical ethics: an ethicist's commentary on housing for fur animals
      versus agricultural animals.

PMID- 23115360
TI  - Associate compensation.

PMID- 23115361
TI  - A call for a national guidance document for veterinary professional conduct in
      Canada.

PMID- 23115362
TI  - Perioperative risk factors for mortality and length of hospitalization in mares
      with dystocia undergoing general anesthesia: a retrospective study.
AB  - This study investigated associations between perioperative factors and
      probability of death and length of hospitalization of mares with dystocia that
      survived following general anesthesia. Demographics and perioperative
      characteristics from 65 mares were reviewed retrospectively and used in a risk
      factor analysis. Mortality rate was 21.5% during the first 24 h post-anesthesia.
      The mean +/- standard deviation number of days of hospitalization of surviving
      mares was 6.3 +/- 5.4 d. Several factors were found in the univariable analysis
      to be significantly associated (P < 0.1) with increased probability of
      perianesthetic death, including: low preoperative total protein, high temperature
      and severe dehydration on presentation, prolonged dystocia, intraoperative
      hypotension, and drugs used during recovery. Type of delivery and day of the week
      the surgery was performed were significantly associated with length of
      hospitalization in the multivariable mixed effects model. The study identified
      some risk factors that may allow clinicians to better estimate the probability of
      mortality and morbidity in these mares.

PMID- 23115363
TI  - Retrospective evaluation of potential causes associated with clinically relevant
      hyperlactatemia in dogs with lymphoma.
AB  - The aim of this study was to determine whether or not canine lymphoma could be
      associated with a clinically relevant type B hyperlactatemia (> 2.5 mmol/L). The
      medical database from the University of Montreal Veterinary Medical Teaching
      Hospital was searched for confirmed cases of canine lymphoma with a blood lactate
      measurement. Information retrieved included stage, clinical observations
      compatible with causes of type A and B hyperlactatemia other than cancer, hepatic
      involvement, and drugs administered. Twenty (40%) dogs were hyperlactatemic. Five
      dogs (10%) were classified as having cancer-related hyperlactatemia. Seventy-five
      percent of hyperlactatemic dogs had clinical evidence of type A hyperlactatemia.
      In addition to lymphoma, 70% of hyperlactatemic dogs had evidence of an
      additional cause of type B hyperlactatemia. A significant association (P = 0.01)
      was identified between corticosteroid administration and hyperlactatemia.
      Cytological, echographic, and/or biochemical tests revealed hepatic changes in
      all hyperlactatemic dogs. Lymphoma alone may not be sufficient to explain
      clinically relevant hyperlactatemia in dogs.

PMID- 23115364
TI  - Clinical outcome of collateral ligament injuries of the tarsus.
AB  - The significance of collateral ligament desmitis of the tarsocrural joint is
      often clinically underestimated, because it is an uncommon injury with a guarded
      prognosis for athletic soundness. The objective of this study was to describe the
      clinical presentation, treatment, and outcome of 12 horses with collateral
      ligament desmitis, along with tarsocrural joint synovitis secondary to
      hemarthrosis. Criteria for inclusion in this study included clinical signs of
      tarsocrural joint synovitis and sonographic evidence of collateral ligament
      desmitis. This retrospective study evaluated horses over an 8-year period. Median
      follow-up after treatment was 5.5 years. Four horses in the study returned to
      their previous level of performance, 6 horses remained lame due to pain in the
      tarsus, 1 was euthanized, and 1 is in convalescence. This study highlights the
      importance of collateral ligament desmitis, and emphasizes the need for early,
      aggressive treatment to prevent the development of osteoarthritis.

PMID- 23115365
TI  - Causes, diagnostic signs, and the utility of investigations of fever in dogs: 50
      cases.
AB  - This study aimed to determine the distribution of diseases causing fever in dogs
      in France. Dogs with fever were reviewed and 50 dogs were retrospectively
      assigned to disease groups. Fever profile and intensity, the time taken to reach
      a diagnosis, and inflammatory status were compared among groups. Almost half the
      dogs (48%) were diagnosed with non-infectious inflammatory diseases. No final
      diagnosis was reached in 14 dogs, 13 of which belonged to owners who did not wish
      to pursue the investigations. No association was found between disease group and
      the intensity of fever, fever profile, or serum C-reactive protein concentration.
      Cytological examinations were most frequently found to be the most important
      determinant for diagnosis (55.7%). This study confirms the predominance of non
      infectious inflammatory diseases as causes of fever. Neither clinical nor
      biological factors were found to be predictive of disease group.

PMID- 23115366
TI  - Cervical discospondylitis in 2 Great Dane puppies following routine surgery.
AB  - Two Great Dane puppies developed cervical discospondylitis following routine
      surgery for sterilization. One animal was affected at C4-C5 and the other at C6
      C7 intervertebral discs. Pseudomonas aeruginosa was obtained in pure culture from
      ultrasound-guided disc aspiration in 1 case. Both animals were successfully
      treated with long-term antibiotics.

PMID- 23115367
TI  - Bilateral ureteral obstruction in a cat due to a ureteral transitional cell
      carcinoma.
AB  - A 15-year-old cat was presented with a history of lethargy and vomiting. Serum
      biochemistry revealed severe azotemia. Ultrasonography revealed a small left
      kidney and hydronephrosis of the right kidney. There was an abdominal mass
      between the kidneys. Necropsy revealed a mass circumflexing both ureters and
      histopathology confirmed a diagnosis of transitional cell carcinoma.

PMID- 23115368
TI  - Diverticulum of the third ventricle and absence of the interthalamic adhesion in
      a dog.
AB  - A 10-month-old male Pomeranian dog was examined for neurological abnormalities
      consistent with diffuse forebrain and cerebellar disease. Based on ultrasound and
      magnetic resonance imaging (MRI) a diagnosis of diverticulum of the third
      ventricle, partial agenesis of the corpus callosum, and absence of the
      interthalamic adhesion was made. As conservative treatment was unsuccessful, a
      ventriculoperitoneal shunt was placed.

PMID- 23115369
TI  - Clinical, ultrasonographic, and pathologic findings in 70 camels (Camelus
      dromedarius) with Johne's disease.
AB  - This study evaluated the use of ultrasonography for the diagnosis of Johne's
      disease in camels (Camelus dromedarius). Seventy camels with confirmed Johne's
      disease were examined by ultrasonography and subsequent necropsy; 15 healthy
      camels were included as controls. The most outstanding findings were visible
      enlargement of the mesenteric lymph nodes in 52 (74%) camels. Lesions had either
      echogenic (26%; n = 18) or anechoic (69%; n = 48) capsule and the contents were
      either anechoic (21%; n = 15), echogenic (27%; n = 19), or heterogeneous (46%; n
      = 32). Clumps of echogenic tissue interspersed with fluid pockets were imaged
      between the intestinal loops in 9 (13%) camels. There was mild, moderate, or
      severe thickening and corrugation of the intestinal wall, excessive anechoic
      fluid in the abdominal cavity in 18 (26%) camels, increased hepatic brightness in
      30 (43%) camels, and pericardial and pleural effusions in 22 (31%) camels.
      Sensitivity values for detecting intestinal lesions and enlarged mesenteric lymph
      nodes were 95% and 84%, respectively.

PMID- 23115370
TI  - Primary cutaneous undifferentiated round cell tumor with concurrent polymyositis
      in a dog.
AB  - A cutaneous poorly differentiated round cell tumor with concurrent, non
      suppurative, polymyositis was diagnosed in a hovawart dog. Histochemical
      staining, immunohistochemistry, and transmission electron microscopy findings
      suggested that the tumors cells were of myeloid, or possibly natural killer cell
      origin. The possibility that the concurrent polymyositis may represent a pre
      neoplastic or paraneoplastic process is discussed.

PMID- 23115371
TI  - Clostridium perfringens type A fatal acute hemorrhagic gastroenteritis in a dog.
AB  - The morning after participating in a dog show, a 2-year-old Pomeranian dog was
      found dead in a pool of bloody feces. Necropsy revealed hemorrhagic
      gastroenteritis of the entire gastrointestinal tract, with many Gram-positive
      bacilli on the surface and in the lumen and crypts of the intestine. Enterotoxin
      positive type A Clostridium perfringens were isolated in large numbers. This
      dramatic case of fatal C. perfringens gastroenteritis highlights the need to
      better understand the role of this bacterium in enteric disease of dogs.

PMID- 23115373
TI  - Sick sinus syndrome in a dog: treatment with dual-chambered pacemaker
      implantation.
AB  - A 2-year-old male castrated boxer dog was presented because of a history of
      syncope. Electrocardiogram tracings obtained with a cardiac event monitor showed
      bradycardia culminating in asystole. Sick sinus syndrome was diagnosed and
      treated with transvenous implantation of a dual-chambered permanent pacemaker.

PMID- 23115372
TI  - Primary central nervous system B-cell lymphoma in a young dog.
AB  - This report describes a primary central nervous system B-cell lymphoma in a 3
      year-old intact female Maltese dog. Canine primary central nervous system
      lymphomas constitute about 4% of all intracranial primary neoplasms, but
      comprehensive histopathologic classifications have rarely been carried out. This
      is the first report of this disease in a young adult dog.

PMID- 23115374
TI  - Diagnostic ophthalmology. Partial deflated uveal cyst.

PMID- 23115375
TI  - PHR's focus on infectious diseases.

PMID- 23115376
TI  - The million heartsTM initiative: progress in preventing heart attacks and
      strokes.

PMID- 23115377
TI  - Using ICD-9-CM E-codes in addition to chief complaint keyword searches for
      identification of animal bite-related emergency department visits.

PMID- 23115380
TI  - Achieving an AIDS-free generation: it's the details that matter.

PMID- 23115381
TI  - Selecting nonpharmaceutical strategies to minimize influenza spread: the 2009
      influenza A (H1N1) pandemic and beyond.
AB  - Shortly after the influenza A (H1N1) 2009 pandemic began, the U.S. government
      provided guidance to state and local authorities to assist decision-making for
      the use of nonpharmaceutical strategies to minimize influenza spread. This
      guidance included recommendations for flexible decision-making based on outbreak
      severity, and it allowed for uncertainty and course correction as the pandemic
      progressed. These recommendations build on a foundation of local, collaborative
      planning and posit a series of questions regarding epidemiology, the impact on
      the health-care system, and locally determined feasibility and acceptability of
      nonpharmaceutical strategies. This article describes -recommendations and key
      questions for decision makers.

PMID- 23115382
TI  - The highest attainable standard of evidence (HASTE) for HIV/AIDS interventions:
      toward a public health approach to defining evidence.
AB  - OBJECTIVES: Evidence-driven decisions have become a standard for health
      interventions, policy, and programs. While randomized controlled trials (RCTs)
      are encouraged for public health interventions, there are limitations with RCTs
      as the gold standard of evidence for HIV interventions. We developed a novel
      system of evaluating evidence for assessing HIV preventive interventions termed
      the Highest Attainable Standard of Evidence (HASTE). METHODS: The HASTE system
      focuses on triangulation of three distinct categories of evidence: efficacy data,
      implementation data, and plausibility. We conducted systematic reviews, including
      experimental and observational data, to assess all available interventions for
      men who have sex with men (MSM). We collected implementation and programmatic
      data using a global electronic consultation, Internet searches, and in-person
      consultations. We assessed plausibility with expert analyses of both biological
      and public health evidence. RESULTS: HASTE includes four grades of evidence:
      Strong (Grade 1), Conditional (Grade 2), Insufficient (Grade 3), and
      Inappropriate (Grade 4). We used the HASTE system to evaluate the evidence for
      HIV interventions for MSM in low- and middle-income countries. Several
      differences emerged in the strength of recommendation with the use of the HASTE
      system, including strong recommendations for voluntary counseling and testing and
      for structural interventions. CONCLUSIONS: The HASTE system addresses a need for
      an evidence evaluation tool that is specific for HIV interventions and
      facilitates an evaluation of biomedical, behavioral, and structural approaches
      using the highest standard of attainable evidence. HASTE represents a tool that
      balances scientific integrity and practicality in assessing the quality of
      evidence of preventive interventions targeting the most-at-risk populations for
      HIV.

PMID- 23115383
TI  - Knowledge, attitudes, and practices for diagnosing breakthrough varicella in the
      outpatient setting.
AB  - OBJECTIVES: We assessed provider knowledge, attitudes, and practices for the
      management of breakthrough varicella and identified barriers to implementation of
      laboratory testing and reporting. METHODS: We surveyed 145 health-care providers
      (HCPs) from 30 pediatric practices in Philadelphia who did not have a history of
      laboratory testing for breakthrough varicella. The self-administered survey
      instrument collected information on clinicians' practices for management of
      children presenting with rash, infection-control strategies, reporting to public
      health agencies, and laboratory testing. RESULTS: Among the 144 HCPs who
      completed the survey, 73 (51%) had practiced for more than 10 years. While 115
      HCPs (80%) would elect to evaluate a child with rash in the office, only 19 (13%)
      would submit diagnostics. When patients had a known recent exposure to varicella,
      84 HCPs (58%) would use laboratory tests: 40% would use direct fluorescent
      antibody staining on a specimen from a cutaneous lesion, 24% would use polymerase
      chain reaction on a lesion specimen, 21% would use acute and convalescent
      serology, and 10% would use other tests. While waiting for test results, 82 HCPs
      (57%) would advise that the child be kept at home, 39 (27%) would notify the
      local health department, and 33 (23%) would inform the school nurse. CONCLUSION:
      As varicella becomes increasingly uncommon, laboratory confirmation becomes more
      critical for appropriate diagnosis, similar to poliomyelitis and measles. Our
      findings suggest that HCPs need further education regarding laboratory
      confirmation, containment, and reporting of breakthrough varicella.

PMID- 23115384
TI  - Comparison of acute viral hepatitis data quality using two methodologies, 2005
      2007.
AB  - OBJECTIVE: We compared the quality of data reported to the Centers for Disease
      Control and Prevention (CDC) from sites that received funding for acute viral
      hepatitis surveillance through CDC's Emerging Infections Program (EIP) with sites
      that have electronic infrastructure to collect data but do not receive funding
      from CDC to support viral hepatitis surveillance. METHODS: Descriptive analysis
      was conducted on acute hepatitis A, B, and C cases reported from EIP sites and
      National Electronic Disease Surveillance System (NEDSS)-based states (NBS) sites
      from 2005 to 2007. Data were compared for (1) completeness of demographic and
      risk behavior/exposure information; (2) adherence to CDC/Council of State and
      Territorial Epidemiologists (CSTE) case definition for confirmed cases of acute
      hepatitis A, B, and C; and (3) timeliness of reporting to the health department.
      RESULTS: Data reported for sex and age were at least 98% complete for both EIP
      and NBS sites and race/ethnicity was more complete for EIP sites. For acute
      hepatitis A, B, and C, case reports from EIP sites were more likely than those
      from NBS sites to include a "yes" response to at least one risk behavior/exposure
      variable and were more likely to meet the CDC/CSTE case definition. EIP sites
      received case reports in a more timely fashion than did NBS sites. The case
      definition for acute hepatitis C proved problematic for both EIP and NBS sites.
      CONCLUSIONS: Data from the EIP sites were more complete and reported in a more
      timely way to health departments than data from the NBS sites. Funding for follow
      up activities is essential to providing surveillance data of higher quality for
      decision-making and public health response.

PMID- 23115386
TI  - Raw milk in court: implications for public health policy and practice.

PMID- 23115388
TI  - Admissions criteria as predictors of students' academic success in master's
      degree programs at the National Institute of Public Health of Mexico.

PMID- 23115389
TI  - Premature birth: an important but frequently overlooked risk factor for OSA.

PMID- 23115390
TI  - Does the rubber meet the road? Addressing sleep apnea in commercial truck
      drivers.

PMID- 23115391
TI  - Home sleep testing: appropriate screening is the key.

PMID- 23115392
TI  - Sleep and sleep loss: an energy paradox?

PMID- 23115393
TI  - Encouraging Preclinical Findings Regarding the Relationship between Sleep and
      Epilepsy.

PMID- 23115394
TI  - Non-respiratory indications for polysomnography and related procedures in
      children: an evidence-based review.
AB  - OBJECTIVE: This evidence-based review provides a systematic and comprehensive
      review of the literature regarding the utility of polysomnography for the
      evaluation of non-respiratory sleep disorders in children including hypersomnias,
      parasomnias, sleep-related movement disorders, and sleep in other special
      populations. METHODS: A task force of pediatric sleep medicine experts performed
      a systematic review of the literature regarding the use of polysomnography for
      non-respiratory sleep disorders in children. They identified and graded 76 papers
      as evidence. RESULTS: The main results include (1) polysomnography combined with
      the multiple sleep latency test is useful for evaluating disorders of excessive
      somnolence to objectively quantify sleepiness. The results have to be interpreted
      with consideration of the pubertal stage and regularity of the sleep patterns of
      the child; (2) polysomnography is indicated in children with parasomnias or sleep
      related movement disorders who have a high likelihood of having obstructive sleep
      apnea (OSA); (3) polysomnography is not routinely indicated in children with
      enuresis unless there is a high likelihood of OSA; (4) polysomnography can be
      helpful in evaluating children with restless legs syndrome (RLS) and when
      periodic limb movement disorder (PLMD) is suspected. CONCLUSIONS: These findings
      suggest that, in children with non-respiratory sleep disorders, polysomnography
      should be a part of a comprehensive sleep evaluation in selected circumstances to
      determine the nature of the events in more detail or when the suspicion of OSA is
      relatively high.

PMID- 23115395
TI  - Practice parameters for the non-respiratory indications for polysomnography and
      multiple sleep latency testing for children.
AB  - BACKGROUND: Although a level 1 nocturnal polysomnogram (PSG) is often used to
      evaluate children with non-respiratory sleep disorders, there are no published
      evidence-based practice parameters focused on the pediatric age group. In this
      report, we present practice parameters for the indications of polysomnography and
      the multiple sleep latency test (MSLT) in the assessment of non-respiratory sleep
      disorders in children. These practice parameters were reviewed and approved by
      the Board of Directors of the American Academy of Sleep Medicine (AASM). METHODS:
      A task force of content experts was appointed by the AASM to review the
      literature and grade the evidence according to the American Academy of Neurology
      grading system. RECOMMENDATIONS FOR PSG AND MSLT USE: PSG is indicated for
      children suspected of having periodic limb movement disorder (PLMD) for
      diagnosing PLMD. (STANDARD)The MSLT, preceded by nocturnal PSG, is indicated in
      children as part of the evaluation for suspected narcolepsy. (STANDARD)Children
      with frequent NREM parasomnias, epilepsy, or nocturnal enuresis should be
      clinically screened for the presence of comorbid sleep disorders and
      polysomnography should be performed if there is a suspicion for sleep-disordered
      breathing or periodic limb movement disorder. (GUIDELINE)The MSLT, preceded by
      nocturnal PSG, is indicated in children suspected of having hypersomnia from
      causes other than narcolepsy to assess excessive sleepiness and to aid in
      differentiation from narcolepsy. (OPTION)The polysomnogram using an expanded EEG
      montage is indicated in children to confirm the diagnosis of an atypical or
      potentially injurious parasomnia or differentiate a parasomnia from sleep-related
      epilepsy (OPTION)Polysomnography is indicated in children suspected of having
      restless legs syndrome (RLS) who require supportive data for diagnosing RLS.
      (OPTION) RECOMMENDATIONS AGAINST PSG USE: Polysomnography is not routinely
      indicated for evaluation of children with sleep-related bruxism. (STANDARD)
      CONCLUSIONS: The nocturnal polysomnogram and MSLT are useful clinical tools for
      evaluating pediatric non-respiratory sleep disorders when integrated with the
      clinical evaluation.

PMID- 23115396
TI  - Sleep apnea in early childhood associated with preterm birth but not small for
      gestational age: a population-based record linkage study.
AB  - STUDY OBJECTIVES: Investigate the relationship between gestational age and weight
      for gestational age and sleep apnea diagnosis in a cohort of children aged up to
      6 years old. DESIGN: A cohort study, using record linked population health data.
      SETTING: New South Wales, Australia. PARTICIPANTS: 398,961 children, born between
      2000 and 2004, aged 2.5 to 6 years. MEASUREMENTS: The primary outcome was sleep
      apnea diagnosis in childhood, first diagnosed between 1 and 6 years of age.
      Children with sleep apnea were identified from hospital records with the ICD-10
      code G47.3: sleep apnea, central or obstructive. RESULTS: A total of 4,145 (1.0%)
      children with a first diagnosis of sleep apnea were identified. Mean age at first
      diagnosis was 44.2 months (SD 13.9). Adenoidectomy, tonsillectomy, or both were
      common among the children diagnosed with sleep apnea (85.6%). Children born
      preterm compared to term were significantly more likely to be diagnosed with
      sleep apnea (< 32 weeks versus term hazard ratio 2.74 [95% CI: 2.16, 3.49]) this
      remained even after adjustment for known confounding variables. Children born
      small for gestational age were not at increased risk of sleep apnea compared to
      children born appropriate for gestational age, hazard ratio 0.95 (95% CI 0.86
      1.06). CONCLUSIONS: This is the largest study investigating preterm birth and
      sleep apnea diagnosis and suggests that diagnosis of sleep disordered breathing
      is more prevalent in children born preterm, but not those who are small for
      gestational age.

PMID- 23115397
TI  - Portable diagnostic devices for identifying obstructive sleep apnea among
      commercial motor vehicle drivers: considerations and unanswered questions.
AB  - Obstructive sleep apnea (OSA), a syndrome defined by breathing abnormalities
      during sleep, can lead to fatigue and excessive daytime sleepiness (EDS) with an
      increased risk of motor vehicle crashes. Identifying commercial motor vehicle
      operators with unrecognized OSA is a major public health priority. Portable
      monitors (PMs) are being actively marketed to trucking firms as potentially lower
      cost and more accessible alternatives to the reference standard of in-laboratory
      polysomnography (PSG) in the diagnosis of OSA among commercial motor vehicle
      operators. Several factors regarding PMs remain uncertain in this unique patient
      population: their sensitivity and specificity; the cost-benefit ratio of the PMs
      versus PSG; potential barriers from human factors; and evolving technologic
      advancement. Human factors that alter test accuracy are a major concern among
      commercial drivers motivated to gain/maintain employment. Current available data
      using PMs as a diagnostic tool among CMV operators indicate relatively high data
      loss and high loss to follow-up. Loss to follow-up has also been an issue using
      PSG in commercial motor vehicle operators. Furthermore, PM testing and PM results
      interpretation protocols may have no sleep specialist oversight, and sometimes
      minimal physician oversight and involvement. Additional studies comparing
      unattended and unmonitored PMs directly against full in-laboratory PSG are needed
      to provide evidence for their efficacy among commercial motor vehicle operators.

PMID- 23115398
TI  - In-home, self-assembled sleep studies are useful in diagnosing sleep apnea in the
      elderly.
AB  - OBJECTIVES: Obstructive sleep apnea (OSA) is common and treatable among the
      elderly. Yet, few older adults seek evaluation for OSA at sleep disorders
      centers. The authors assessed the feasibility of a two-stage screening procedure
      for obstructive sleep apnea syndrome (OSAS) in a community-based sample of older
      adults. DESIGN: Prospective cohort study. SETTING: Participants' domicile (in
      home) and academic sleep research center. PARTICIPANTS: There were 452 Medicare
      recipients residing in the greater Philadelphia metropolitan area with the
      complaint of daytime sleepiness. INTERVENTIONS: None. MEASUREMENTS AND RESULTS:
      All participants underwent in-home unattended sleep studies that recorded
      airflow, and standard in-laboratory polysomnography. Additional measures included
      symptoms of sleep apnea, body mass index, neck circumference, age, and sex. When
      comparing diagnostic approaches, the best-performing single-stage model was one
      that combined apnea symptoms with age and neck circumference. This model had an
      area under the receiver operating characteristic curve (AUC) of 0.774 and
      negative posttest probability of 1.2%. The best-performing two-stage model
      combined symptoms, neck circumference, age, and sex in the first stage, followed
      by an unattended portable study with a corresponding AUC of 0.85 and negative
      posttest probability of 0.5%. CONCLUSIONS: Unattended, self-assembled, in-home
      sleep studies recording airflow and respiratory effort are most useful if applied
      in tandem with clinical data, including a carefully obtained sleep history. This
      two-stage model is accurate in identifying severe OSAS in older adults and
      represents a practical diagnostic approach for older adults. Incorporating
      clinical data was vital and increased accuracy well above that of unattended
      studies of airflow and effort alone.

PMID- 23115399
TI  - Short sleep duration, glucose dysregulation and hormonal regulation of appetite
      in men and women.
AB  - STUDY OBJECTIVE: To determine the hormonal effects of reducing sleep duration
      under controlled feeding conditions. DESIGN: Randomized, crossover study.
      SETTING: Inpatient. PARTICIPANTS: Twenty-seven normal weight, 30- to 45-yr-old
      men and women habitually sleeping 7-9 hr/night. INTERVENTION: PARTICIPANTS WERE
      STUDIED UNDER TWO SLEEP CONDITIONS: short (4 hr in bed) or habitual (9 hr in bed)
      sleep. A controlled diet was provided for each 4-day study period. MEASUREMENTS
      AND RESULTS: Fasting blood samples were obtained daily and frequent blood samples
      were obtained throughout day 4. The main outcomes measures included glucose,
      insulin, leptin, ghrelin, adiponectin, total glucagon-like peptide 1 (GLP-1) and
      peptide YY(3-36) (PYY(3-36)) concentrations. Body weights were reduced by 2.2 +/-
      0.4 lb and 1.7 +/- 0.4 lb during the habitual and short sleep phases,
      respectively (both P < 0.0001). There was no effect of sleep duration on glucose,
      insulin, and leptin profiles (all P > 0.05). Ghrelin and GLP-1 responses differed
      by sex. Short sleep increased fasting (P = 0.054) and morning (08:00-12:00) (P =
      0.042) total ghrelin in men but not women. The reverse was observed for GLP-1:
      afternoon levels (12:30-19:00) were lower (P = 0.016) after short sleep compared
      with habitual sleep in women but not men. CONCLUSIONS: These data suggest that,
      in the context of negative energy balance, short sleep does not lead to a state
      of increased insulin resistance, but may predispose to overeating via separate
      mechanisms in men and women. CLINICAL TRIAL INFORMATION: Trial registration on
      http://www.clinicaltrials.gov. #NCT00935402.

PMID- 23115400
TI  - Metabolic effects of chronic sleep restriction in rats.
AB  - STUDY OBJECTIVES: Chronic partial sleep loss is associated with obesity and
      metabolic syndrome in humans. We used rats with lesions in the ventrolateral
      preoptic area (VLPO), which spontaneously sleep about 30% less than intact rats,
      as an animal model to study the consequences of chronic partial sleep loss on
      energy metabolism. PARTICIPANTS: Adult male Sprague-Dawley rats (300-365 g).
      INTERVENTIONS: We ablated the VLPO in rats using orexin-B-saporin and
      instrumented them with electrodes for sleep recordings. We monitored their food
      intake and body weight for the next 60 days and assessed their sleep-wake by 24-h
      EEG/EMG recordings on day 20 and day 50 post-surgery. On day 60, after blood
      samples were collected for metabolic profiling, the animals were euthanized and
      the brains were harvested for histological confirmation of the lesion site.
      MEASUREMENTS AND RESULTS: VLPO-lesioned animals slept up to 40% less than sham
      lesioned rats. However, they showed slower weight gain than sham-lesioned
      controls, despite having normal food intake. An increase in plasma ghrelin and a
      decrease in leptin levels were observed, whereas plasma insulin levels remained
      unaffected. As expected from leaner animals, plasma levels of glucose,
      cholesterol, triglycerides, and C-reactive protein were reduced in VLPO-lesioned
      animals. CONCLUSIONS: Chronic partial sleep loss did not lead to obesity or
      metabolic syndrome in rats. This finding raises the question whether adverse
      metabolic outcomes associated with chronic partial sleep loss in humans may be
      due to factors other than short sleep, such as circadian disruption, inactivity,
      or diet during the additional waking hours.

PMID- 23115401
TI  - Association between obstructive sleep apnea and elevated levels of type B
      natriuretic peptide in a community-based sample of women.
AB  - STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with an increased
      risk of cardiovascular disease. One contributory factor may be hemodynamic stress
      due to the negative intrathoracic pressure during each episode of apnea. Type B
      natriuretic peptide (BNP) is secreted by the cardiac ventricles in response to
      volume expansion and pressure load and the authors hypothesized that there would
      be an association between indices of OSA during the night and levels of BNP in
      the morning. SETTING: Community-based in Uppsala, Sweden. PARTICIPANTS: There
      were 349 women who participated. MEASUREMENTS AND RESULTS: Participants underwent
      full-night polysomnography and anthropometric measurements, and answered
      questionnaires about medical conditions and current medication. The morning after
      the polysomnography, blood samples were drawn for analysis of plasma BNP, C
      reactive protein, creatinine, and hemoglobin. There was an increase in mean BNP
      as the severity of sleep apnea increased, increasing from a mean value of 8.5
      ng/L among women with an apnea-hypopnea index (AHI) < 5 to 18.0 ng/L in women
      with an AHI >= 30. Elevated BNP levels (>= 20 ng/L) were found in 29.8% of the
      women, whereas 70.2% had normal levels. The odds ratio was 2.2 for elevated BNP
      levels for women with an AHI of 5-14.9 in relation to women with an AHI < 5, 3.1
      for women with an AHI of 15-29.9, and 4.6 for women with an AHI >= 30 after
      adjustment for age, body mass index, systolic blood pressure, antihypertensive
      drugs, and creatinine. CONCLUSIONS: There is a dose-response relationship in
      women between the severity of sleep apnea during the night and the levels of BNP
      in the morning.

PMID- 23115402
TI  - A randomized, double-blind, placebo-controlled study of an oral, extended-release
      formulation of phentermine/topiramate for the treatment of obstructive sleep
      apnea in obese adults.
AB  - STUDY OBJECTIVES: To evaluate safety and efficacy of phentermine 15 mg plus
      extended-release topiramate 92 mg for treatment of moderate to severe obstructive
      sleep apnea (OSA) in obese adults. DESIGN: This phase 2, randomized, double
      blind, placebo-controlled study included 2-week screening and 28-week treatment
      periods. Overnight polysomnography was performed at baseline, Week 8, and Week
      28. SETTING: Single-center study conducted from August 2008 to September 2009.
      PARTICIPANTS: Forty-five subjects with moderate to severe OSA not receiving
      positive airway pressure (PAP) treatment with body mass index of 30-40 kg/m(2).
      INTERVENTIONS: Subjects were randomized to receive placebo (n = 23) or
      phentermine 15 mg plus extended-release topiramate 92 mg (n = 22). Both groups
      received lifestyle-modification counseling. MEASUREMENTS AND RESULTS: Primary
      endpoint, change in apnea-hypopnea index (AHI), significantly favored phentermine
      15 mg plus extended-release topiramate 92 mg (-31.5 events/h, 95% CI: -40.0, 
      22.9) over placebo (-16.6 events/h, 95% CI: -25.0, -8.2) at Week 28 (P =0.0084).
      At Week 28, there was a 10.2% (95% CI: -12.7, -7.6; 10.8 kg, 95% CI: -13.5, -8.0)
      mean decrease in weight in the phentermine 15 mg plus extended-release topiramate
      92 mg group compared with 4.3% (95% CI: -6.6, -2.0; 4.7 kg, 95% CI: -7.2, -2.2)
      in the placebo group (P = 0.0006) and a positive, significant (P = 0.0003)
      correlation between percent change in weight and change in AHI. Significant
      improvements in overnight oxygen saturation and reduction in blood pressure
      compared with placebo were observed. Phentermine 15 mg plus extended-release
      topiramate 92 mg was well tolerated with low adverse event rates. CONCLUSIONS:
      Phentermine 15 mg plus extended-release topiramate 92 mg induced significant
      weight reductions and concomitant improvements in OSA and related symptoms vs
      placebo. This suggests weight loss mediated by phentermine 15 mg plus extended
      release topiramate 92 mg may be useful in treatment of moderate to severe OSA in
      obese subjects unable or unwilling to comply with PAP treatment.

PMID- 23115403
TI  - Influence of hypoxia and hypercapnia on sleep state-dependent heart rate
      variability behavior in newborn lambs.
AB  - STUDY OBJECTIVES: Although hypercapnia and/or hypoxia are frequently present
      during chronic lung disease of infancy and have also been implicated in sudden
      infant death syndrome (SIDS), their effect on cardiac autonomic regulation
      remains unclear. The authors' goal is to test that hypercapnia and hypoxia alter
      sleep-wake cycle-dependent heart rate variability (HRV) in the neonatal period.
      DESIGN: Experimental study measuring HRV during sleep states in lambs randomly
      exposed to hypercapnia, hypoxia, or air. SETTING: University center for perinatal
      research in ovines (Sherbrooke, Canada). INSERM-university research unit for
      signal processing (Rennes, France). PARTICIPANTS: Six nonsedated, full-term
      lambs. INTERVENTIONS: Each lamb underwent polysomnographic recordings while in a
      chamber flowed with either air or 21% O(2) + 5% CO(2) (hypercapnia) or 10% O(2) +
      0% CO(2) (hypoxia) on day 3, 4, and 5 of postnatal age. MEASUREMENTS AND RESULTS:
      Hypercapnia increased the time spent in wakefulness and hypoxia the time spent in
      quiet sleep (QS). The state of alertness was the major determinant of HRV
      characterized with linear or nonlinear methods. Compared with QS, active sleep
      (AS) was associated with an overall increase in HRV magnitude and short-term self
      similarity and a decrease in entropy of cardiac cycle length in air. This AS
      related HRV pattern persisted in hypercapnia and was even more pronounced in
      hypoxia. CONCLUSION: Enhancement of AS-related sympathovagal coactivation in
      hypoxia, together with increased heart rate regularity, may be evidence that AS +
      hypoxia represent a particularly vulnerable state in early life. This should be
      kept in mind when deciding the optimal arterial oxygenation target in newborns
      and when investigating the potential involvement of hypoxia in SIDS pathogenesis.

PMID- 23115404
TI  - Efficacy of eight months of nightly zolpidem: a prospective placebo-controlled
      study.
AB  - STUDY OBJECTIVES: To evaluate the long-term (8 months) efficacy of zolpidem in
      adults with chronic primary insomnia using polysomnography. DESIGN: Randomized,
      double-blind, placebo-controlled clinical trial. SETTING: Sleep disorders and
      research center. PARTICIPANTS: Healthy participants (n = 91), ages 23-70, meeting
      DSM-IV-TR criteria for primary insomnia. INTERVENTIONS: Nightly zolpidem, 10 mg
      (5 mg for patients > 60 yrs) or placebo 30 minutes before bedtime for 8 months.
      MEASUREMENTS AND RESULTS: Polysomnographic sleep parameters and morning subject
      assessments of sleep on 2 nights in months 1 and 8. Relative to placebo, zolpidem
      significantly increased overall total sleep time and sleep efficiency, reduced
      sleep latency and wake after sleep onset when assessed at months 1 and 8.
      Overall, subjective evaluations of efficacy were not shown among treatment
      groups. CONCLUSIONS: In adults with primary insomnia, nightly zolpidem
      administration remained efficacious across 8 months of nightly use. CLINICAL
      TRIAL INFORMATION: ClinicalTrials.gov Identifier: NCT01006525; Trial Name: Safety
      and Efficacy of Chronic Hypnotic Use;
      http://clinicaltrials.gov/ct2/show/NCT01006525.

PMID- 23115405
TI  - Trajectories of sleep complaints from early midlife to old age: longitudinal
      modeling study.
AB  - STUDY OBJECTIVES: To estimate trajectories of sleep lost over worry as a function
      of age, using longitudinal modeling, and compare these trajectories with those
      for insomnia symptoms. DESIGN AND SETTING: Data from two prospective,
      occupational cohorts (the Whitehall II and Finnish Public Sector studies)
      comprising 84,384 observations from four to eight repeat measurements in 1985
      2010. PARTICIPANTS: There were 16,408 men and women age 34-79 yr. MEASUREMENTS
      AND RESULTS: Age-related trajectories of sleep lost over worry and insomnia
      symptoms (sleep initiation or maintenance problems, nonrefreshing sleep) were
      estimated using repeated-measures log-binomial regression analysis and
      generalized estimating equations. These analyses were adjusted for year of birth
      and time of measurement to minimize confounding by cohort or period effects. The
      prevalence ratio for insomnia symptoms was higher in older age groups compared
      with participants age 34-45 yr. In contrast, the age-related trajectory of sleep
      lost over worry included two phases: a period of high prevalence of sleep
      complaints at age 34-60 yr followed by a declining trajectory at older ages.
      Compared with participants age 34-45 yr, prevalence ratios for sleep lost over
      worry were 0.63 (0.49-0.80) and 0.59 (0.41-0.84) in the Whitehall II study
      participants ages 61-65 and 71-79 years. Corresponding figures were 0.62 (0.52
      0.75) and 0.46 (0.32-0.66) in the Finnish Public Sector study. CONCLUSION: This
      study shows a general age-related decrease in sleep lost over worry between late
      midlife and old age, a pattern strikingly different from the age-related increase
      in insomnia symptoms.

PMID- 23115406
TI  - Characterizing sleep behavior of the wild black rhinoceros (Diceros bicornis
      bicornis).
AB  - STUDY OBJECTIVES: The objectives of this study were to characterize sleep
      patterns and determine factors, including sex, age, season, and environmental
      pressures, that influence sleep in the endangered black rhinoceros (rhino;
      Diceros bicornis bicornis). DESIGN: To noninvasively observe sleep behavior of
      wild rhinos, digital infrared cameras were erected on poles at two bedding sites
      from September 2009 to March 2010. SETTING: The study site was located in South
      Africa's Addo Elephant National Park (AENP) in the Main Camp (Addo) and Nyathi
      sections. PARTICIPANTS: A total of 2,417 photos captured rhino sleep behavior on
      eight individual rhinos during 40 separate sleeping bouts (Addo, n = 15; Nyathi,
      n = 25). INVENTIONS: N/A. RESULTS: Results demonstrated that age and season did
      not affect rhino sleep behavior (P > 0.05); however, sex did influence the length
      of sleep bouts with males (n = 27; mean, 105.6 +/- 11.3 min; range, 14.0-202.0
      min) sleeping longer (F(1,48) = 6.93, P = 0.01) than females (n = 13; mean, 58.6
      +/- 10.4 min; range, 11.0-132.0 min). Park section did not influence the length
      of sleep episodes, but did affect (rw(40) = 0.88; P < 0.025) the time at which
      rhinos slept (Addo, 20:00-24:00; Nyathi, 20:00-04:00). CONCLUSIONS: This is the
      first study to characterize sleep behavior in wild black rhinos. This study
      resulted in a greater understanding of the biologic factors that affect sleep in
      wild rhinos and can provide information to assist their management and
      conservation.

PMID- 23115407
TI  - A combined field and laboratory design for assessing the impact of night shift
      work on police officer operational performance.
AB  - OBJECTIVES: This study assessed the utility of a combined field and laboratory
      research design for measuring the impact of consecutive night shift work on the
      sleepiness, vigilance, and driving performance of police patrol officers. DESIGN:
      For police patrol officers working their normal night shift duty cycles,
      simulated driving performance and psychomotor vigilance were measured in a
      laboratory on two separate occasions: in the morning after the last of five
      consecutive 10.7-h night shifts, and at the same time in the morning after three
      consecutive days off duty. Order of participation in conditions was randomized
      among subjects. SETTING: Subjects experienced manipulation of sleep schedules due
      to working night shifts in a real operational environment, but performance
      testing was conducted under controlled laboratory conditions. PARTICIPANTS: N =
      29 active-duty police patrol officers (27 male, 2 female; age 37.1 +/- 6.3 years)
      working night shift schedules participated in this study. RESULTS: Simulated
      driving performance, psychomotor vigilance, and subjective sleepiness were
      significantly degraded following 5 consecutive night shifts as compared to 3
      consecutive days off duty, indicating that active-duty police officers are
      susceptible to performance degradation as a consequence of working nights.
      CONCLUSIONS: This combined field and laboratory research design succeeded in
      bridging the gap between the realism of the operational environment and the
      control of laboratory performance testing, demonstrating that this is a useful
      approach for addressing the relationship between shift work induced fatigue and
      critical operational task performance.

PMID- 23115408
TI  - Evidence-based evaluation of physiological effects of standing and walking in
      individuals with spinal cord injury.
AB  - Spinal Cord Injury (SCI) is damage to spinal cord, which is categorized according
      to the extent of functional loss, sensation loss and inability of the subjects to
      stand and walk. The patients use two transportation systems including orthosis
      and wheelchair. It was claimed that standing and walking bring some benefits such
      as decreasing bone osteoporosis, prevention of pressure sores, and improvement of
      the function of the digestive system for SCI patients. Nevertheless, the question
      of wether or not there is enough evidence to support the effect of walking with
      orthosis on the health status of the subjects with SCI remains unanswered. In
      order to answer this question a review of the relevant literature was carried
      out. The review of the literature showed that evidence reported in the literature
      regarding the effectiveness of orthoses for improving the health condition of SCI
      patients was controversial. Many investigators had only used the comments of the
      users of orthoses. The benefits mentioned in various research studies regarding
      the use of orthosis included decreasing bone osteoprosis, preventing joint
      deformity, improving bowl and bladder function, improving digestive system
      function, decreasing muscle spasm, improving independent living, and improving
      respiratory and cardiovascular systems function. The findings of the studies
      reviewed also showed that improving the independent living and physiological
      health of the subjects were the only two benefits, which were supported by strong
      evidence. The review of the literature suggests that most published studies are
      in fact surveys, which collected questionnaire-based information from the users
      of orthosis.

PMID- 23115409
TI  - Glycemic Control among Pregnant Diabetic Women on Insulin Who Fasted During
      Ramadan.
AB  - BACKGROUND: Ramadan fasting for pregnant women with diabetes remains
      controversial and underreported. The objective of this study was to determine the
      glycemic control in pregnant diabetic women on insulin who fasted during Ramadan.
      METHODS: This was a retrospective study carried out over a period of three years
      including pregnant diabetic women, who were on short-acting, intermediate-acting,
      or a combination of them, and opted to carry out Ramadan fasting. Glycemic
      control was assessed before, middle and after Ramadan fasting. RESULTS: Thirty
      seven women opted to fast with 24 (64.9%) of them had type 2 diabetes mellitus
      and 83.8% of them required combined insulin (short- acting, intermediate-acting)
      therapy. The age of the participants was 32.13+/-4.68 years, and the age of their
      pregnancies was 25.60+/-7.12 weeks when the study was performed. The median
      number of days fasted was 25 days, and most of the women were able to fast for
      more than 15 days. There was no difference between glycemic control of type 2
      diabetes mellitus and gestational diabetes mellitus women prior to fasting. In
      the middle of Ramadan, serum fructosamine decreased in both groups. However, only
      serum HbA1c reduced in gestational diabetes mellitus after Ramadan. CONCLUSION:
      the findings indicate that pregnant diabetic women on insulin were able to fast
      during Ramadan and that their glycemic control was improved during fasting
      period. They may also suggest that instead of absolute ban on fasting for
      pregnant diabetic women more practical approach and close consultation with
      health care providers might be more helpful.

PMID- 23115410
TI  - The expression of heme oxygenase-1 in human-derived cancer cell lines.
AB  - BACKGROUND: Heme oxygenase-1 (HO-1) is a cytoprotective and antiapoptotic enzyme,
      which has been involved in maintaining cellular homeostasis, and plays an
      important protective role by modulating oxidative injury. Up-regulation of (HO-1)
      has contributed to tumorogenicity of some cancers. In this study we investigated
      the expression pattern of the HO-1, in five different human-derived cancer cell
      lines with high incidence in Iran. METHODS: Total cell RNA were extracted from
      HepG2 (hepato carcinoma), A549 (lung adenocarcinoma), MCF-7 (breast cancer), K562
      (myeloid leukemia) and LS174T (colon cancer) cell lines. Human embryonic kidney
      (HEK293) cell line was used as a control. cDNAs were synthesized and expression
      of HO-1 was examined using RT-PCR. RESULTS: The expression of HO-1 was not
      detected in the control cell line (HEK293), but it was observed to express
      following ultraviolet (UV) exposure indicating that HO-1 is not constantly
      expressed. The examined cancer cell lines constitutively expressed different
      variety of HO-1 on mRNA level. Strong expression of HO-1 was observed in HepG2,
      MCF-7 and A549 cells. A moderate expression of HO-1 was observed in K562 cells,
      and LS174T cells showed no expression of HO-1. CONCLUSION: Heme oxygenase-1 could
      be considered as a new marker in the diagnosis of some cancers, especially
      hepatomacarcinoma. Our results also suggest that up-regulation of HO-1 may
      contribute to tumorogenicity of some cancers. Therefore, the combination of gene
      silencing effect of HO-1 and chemotherapy might be considered as a new modality
      for the treatment of cancers in which the expression HO-1 is up-regulated.

PMID- 23115411
TI  - Histomorphological Alterations in the Prostate Gland and Epithelium of
      Seminiferous Tubule of Sprague-Dawley Rats Treated with Methanolic Extract of
      Momordica charantia Seeds.
AB  - BACKGROUND: There is yet a dearth of literature on the antifertility effect of
      Momordica charantia on the male reproductive system. The aim of this study was to
      determine the effect of graded oral doses of methanolic seed extract of Momordica
      charantia on the histology of prostate gland and seminiferous tubules of rats.
      METHODS: Forty male Sprague-Dawley rats, weighing 176+/-7 g were assigned
      randomly into four main groups A to D of 10 rats per group. Groups A to C
      received daily oral doses of15, 25 or 50 mg/100 g body weight of the seed extract
      for 56 days. Group D (control) received physiological saline. In each group, five
      rats were sacrificed on day 57, the remaining half on day 113 (56 days after
      withdrawal of the extract). The testes and prostate were processed for
      histological examination. RESULTS: There was a dose-related alteration in the
      cytoarchitecture of seminiferous tubules with marked reduction in spermatogenic
      series. The prostate gland showed dilatation as well as increased intraluminal
      secretions with increasing dose. Moreover, there was a significant recovery of
      prostate tissue as the sections were similar to their control counterpart.
      CONCLUSION: the findings of the present study indicate that methanolic extract of
      Momordica charantia seeds caused reversible histological alterations in the
      prostate and testes of Sprague-Dawley rats.

PMID- 23115412
TI  - Polymerase chain reaction, bacteriologic detection and antibiogram of bacteria
      isolated from otitis media with effusion in children, shiraz, iran.
AB  - BACKGROUND: Otitis media with effusion is one of the leading causes of hearing
      loss in children. Effective treatment of effusion in the middle ear requires
      appropriate empirical treatment and characterization of responsible pathogens.
      Objective of the present study was to detect pathogens in clinical samples from
      patients with otitis media with effusion in our area and to determine the
      sensitivity profile of isolated organisms to commonly used antibiotics. METHODS:
      Sixty three samples of middle ear effusion were aseptically obtained from 36
      children, who had been treated up to at least two weeks before sampling. They
      were analyzed using standard bacteriological and multiplex polymerase chain
      reaction (PCR) assays. Antibiotic susceptibility tests were also performed.
      RESULTS: PCR analysis showed that DNA of Streptococcus pneumoniae, Haemophilus
      influenzae and Moraxella catarrhalis were present in 60 (95.2%) of the samples.
      The culture-positive effusion for Streptococcus Pneumoniae, HaemophilusInfluenzae
      and Moraxella catarrhalis was 34.9%. Almost all isolates of Streptococcus
      pneumoniaee were sensitive to ciprofloxacin and erythromycin, and none of them
      was sensitive to co-trimoxazole. None of H. Influenzae isolates was sensitive to
      erythromycin, cefixim, co-trimoxazole, ampicillin and amoxicillin. None of M.
      Catarrhalis isolates was sensitive to ceftriaxone, co-trimoxazole, ampicillin and
      amoxicillin. CONCLUSION: Compared with other studies using PCR method, the number
      of H.influenza isolates was in higher in the present study (95.2%). Antibiotic
      sensitivity profiles of pathogens isolated in this study were different from
      others. Thus, we can determine empirical antibiotic therapy based on sensitivity
      profile in our geographic area.

PMID- 23115413
TI  - Histological changes in the fracture callus following the administration of water
      extract of piper sarmentosum (daun kadok) in estrogen-deficient rats.
AB  - BACKGROUND: The fracture healing is impaired in osteoporosis. Piper sarmentosum
      is a plant, which contains potent antioxidant, naringenin that may enhance
      fracture healing. The present histological study aimed to determine the effects
      of water extract of Piper sarmentosum on the late phase of fracture healing in
      estrogen-deficient rats. METHODS: Twenty four female Sprague-Dawley rats (200-250
      gm) were obtained. Six rats underwent sham operation and the rest were
      ovariectomized. Six weeks post-ovariectomy all the rats were fractured at the mid
      diaphysis of the right femur and a K-wire was inserted for internal fixation. The
      sham group was given vehicle (normal saline) and the ovariectomized group was
      randomly subdivided into three groups: (i) ovariectomized-control group
      supplemented with vehicle; (ii) ovariectomized+estrogen replacement therapy group
      treated with estrogen (100 ug/kg/day) and (iii) ovariectomized+Piper sarmentosum
      group treated with Piper sarmentosum water extract (125 mg/kg). Following six
      weeks of treatment, the rats were sacrificed and the right femora were harvested
      for histological assessment of fracture callus. RESULTS: The ovariectomized
      control group showed a significant delay in fracture healing compared to the
      sham, ovariectomized-estrogen replacement therapy and ovariectomized-Piper
      sarmentosum groups. The median callus score for the ovariectomized-Piper
      sarmentosum group was 4.50 (range, 4-5), which was significantly higher than the
      median callus score 3.50 (range, 3-4) for the ovariectomized-control group
      (P=0.019). However, there was no significant (P>0.05) difference in the callus
      score among the sham, ovariectomized-estrogen replacement therapy and
      ovariectomized-Piper sarmentosum groups groups. CONCLUSION: Treatment with water
      extract of Piper sarmentosum proved beneficial in the fracture healing in
      estrogen-deficient rats.

PMID- 23115414
TI  - Hippocampal GABA(A) Receptor and Pain Sensitivity during Estrous Cycle in the
      Rat.
AB  - BACKGROUND: Estradiol and progesterone as well as hippocampal GABA(A) receptors
      are believed to play a role in the modulation of pain. The aim of present study
      was to investigate the effect of intrahippocampal injections of GABA(A) receptor
      agonist (muscimol) and GABA(A) receptor antagonist (picrotoxin) on pain
      sensitivity during estrous cycle. METHODS: Pain sensitivity was evaluated in rats
      by formalin test during all stages of estrous cycle. Animals were divided into
      five groups including; 1- control (intact animal); 2- sham 1 receiving 0.75 ul
      artificial cerebrospinal fluids (ACSF); 3- sham 2 receiving 0.75 ul alcoholic
      ACSF; 4- experimental 1 receiving 250 or 500 ug/rat of muscimol in 0.75 ul
      vehicle, and 5- experimental 2 receiving 20 or 30 ug/rat picrotoxin in 0.75 ul
      vehicle. Data were analyzed by Kruskal-Wallis followed by Tucky's test for
      pairwise comparisons using a P value of <=0.50 for statistical significance.
      RESULTS: Muscimol significantly (P<0.05) decreased pain sensitivity in all stages
      of estrous cycle, and the analgesic effect was higher during proestrus and estrus
      stages of estrous cycle than that during metestrus and diestrus stages.
      Picrotoxin significantly (P<0.05) increased pain sensitivity in all stages of
      estrous cycle, and such a hyperalgesic effect was lower during proestrus and
      estrus stages of estrous cycle than that during metestrus and diestrus stages.
      CONCLUSION: The findings of the present study indicate that the role of
      hippocampal GABA(A) receptor in the control of the pain sensitivity can be
      modulated by variation in gonadal steroids during different stages of the estrous
      cycle.

PMID- 23115415
TI  - Two-Point Discrimination Test in the Treatment of Right-handed Females with
      Lumbosacral Radiculopathy.
AB  - Non-somatic causes of pain may aggravate painful complaints and complicate the
      conservative management of diseases such as lumbo-sacral disk root disease. The
      two-point discrimination test has been used for assessment of diseases, which
      change patients' skin sensation. This study aims to find out how applicable is
      two-point discrimination test in the conservative treatment of lumbo-sacral disk
      diseases. Twenty right-handed females suffering from unilateral lumbo-sacral disk
      disease were admitted for a conservative treatment from 2006 to 2009. The
      treatment consisted of a week bed rest, physiotherapy, and medication. They were
      subjected to straight leg raising tests, and their pains were evaluated using
      visual analog scale. The values of two-point discrimination test were obtained
      bilaterally for L(4), L(5) and S(1 )dermatomes. Changes between the involved and
      intact lower limbs as well as values of two-point discrimination test before and
      after the treatment were also compared. In addition, the correlation between the
      outcome of two-point discrimination, straight leg raising tests, or pain scores
      were evaluated. There was a significant (P<0.001) difference between the changes
      in the values of two-point discrimination test, pain scales, or straight leg
      raising tests in the involved and intact limbs before and after the treatment.
      However, correlation among variables did not reach statistical significance
      (P<0.94, r=0.017). The results indicated that although two-point discrimination
      test is a feasible and objective tool to evaluate patients' improvements during
      the conservative management of lumbo-sacral disk diseases, there were no strong
      correlations between two-point discrimination test and straight leg raising
      tests, or pain scale.

PMID- 23115416
TI  - Mass Measles Vaccination Campaign in Aila Cyclone-Affected Areas of West Bengal,
      India: An In-depth Analysis and Experiences.
AB  - Disaster-affected populations are highly vulnerable to outbreaks of measles.
      Therefore, a mass vaccination against measles was conducted in Aila cyclone
      affected blocks of West Bengal, India in July 2009. The objectives of the present
      report were to conduct an in depth analysis of the campaign, and to discuss the
      major challenges. A block level micro-plan, which included mapping of the
      villages, health facilities, temporary settlements of disaster-affected
      population, communications available, formation of vaccination team, information
      education communication, vaccine storage, waste disposal, surveillance for
      adverse events following immunization, supervision and monitoring was developed.
      The rate of six months to five years old children, who were vaccinated by measles
      vaccine, was 70.7% and that of those who received one dose of vitamin A was
      71.3%. Wastage factor for vaccine doses and auto-disable syringes were 1.09 and
      1.07, respectively. Only 13 cases of adverse events following immunization were
      reported. An average of 0.91 puncture-proof containers per vaccination session
      was used. Despite the major challenges faced due to difficult to reach areas,
      inadequate infrastructure, manpower and communication, problems of vaccine
      storage and transport, the campaign achieved a remarkable success regarding
      measles vaccine coverage, improvements of cold chain infrastructure, formulating
      an efficient surveillance and reporting system for adverse events following
      immunization, building self-confidence of the stakeholders, and developing a
      biomedical waste disposal system.

PMID- 23115417
TI  - A Comparison of the effectiveness of Mammographic Film-Screen and Standard Film
      Screen in the Detection of Small Bone Fractures.
AB  - The use of mammography film-screen is limited in general radiography. The purpose
      of this study was to compare the effectiveness of mammographic film-screen and
      standard film-screen systems in the detection of small bone fractures.
      Radiographs were taken from patients' extremities and neck areas using
      mammography film-screen and standard film-screen (n=57 each). Fourteen other
      radiographs were taken from other views (predominantly oblique views), making a
      total number of 128 radiographs. Paired radiographs, taken from the same areas,
      were compared by two radiologists in terms of image visual sharpness, presence of
      bony fractures, and soft tissue injuries. The surface dose received by patients
      in the two systems was also compared. The radiographs taken by mammography film
      screen had a statistically better visual sharpness compared to those taken by the
      standard film-screen system. However, there was no statistically significant
      difference between the diagnostic accuracy of the two systems. Mammography film
      screen was able to detect only one out of 57 lesions, whereas standard film
      screen system did not detec any lesion. The surface dose received by patients in
      mammography film-screen was higher than that in standard film-screen system. The
      findings of the present study suggest that mammography film-screen may be
      recommended as a diagnostic tool for the detection of small fractures of tinny
      parts of body such as fingers, hand or foot. They also suggest that mammography
      film-screen has no advantage over standard film-screen for radiography of thick
      body parts such as neck and knee.

PMID- 23115418
TI  - Spontaneous rupture and hemorrhage of adrenal pseudocyst presenting with acute
      abdomen and shock.
AB  - Adrenal gland pseudocysts are not common conditions, and most of them are
      nonfunctional and asymptomatic. However, large pseudocysts may causes abdominal
      discomfort and have compressive effects on adjacent organs. They may rupture
      spontaneously or after trauma, and lead to retroperitoneal hemorrhage and
      surgical emergency. Herein, we report a case of 21-year-old female who presented
      with acute abdomen and hemorrhagic shock due to spontaneous rupture of adrenal
      pseudocyst. She was treated successfully by open surgery, removal of adrenal
      pseudocyst and unilateral adrenalectomy.

PMID- 23115419
TI  - Malignant phylloides tumor of breast in a pregnant woman with coincidental
      nulliparous vaginal prolapse.
AB  - Malignant phylloides tumor is a relatively rare and rapidly growing tumor of the
      breast. Presentation during pregnancy is uncommon. Reports regarding malignancy
      in these tumors differ greatly in incidence, and most of them are stromal
      malignancies. We report this case in which 24-year old primigravid patient in the
      36(th) week of her pregnancy had a malignant phylloides tumor of breast with
      sudden growth and fine needle aspiration cytology of the breast was positive for
      malignancy. Ultimately after her caesarean delivery, excision biopsy was in favor
      of a malignant process. Pregnancy with nulliparous prolapse is also a rare
      condition. Those conditions are not associated with each other, but presence of
      two rare conditions in the same time in the same person is unique.

PMID- 23115420
TI  - A Young Lady with a Swelling over the Back: A Rare Case of Tuberculosis.
AB  - Musculoskeletal tuberculosis accounts for 1-2% of all types of tuberculosis.
      Tubercular abscess of the chest wall accounts for 1-5% of all cases of
      musculoskeletal tuberculosis. Herein, we report a case of tubercular abscess of
      the chest wall. The occurrence of caries rib and cold abscess of the chest wall
      with concomitant pulmonary tuberculosis, and tubercular lymphadenitis of neck and
      mediastinum has rarely been described in an immunocompetent individual. The
      rarity of our case lies in the fact that the patient was immunocompetent with
      cold abscess due to caries rib, with rare association of pulmonary tuberculosis
      and tubercular lymphadenitis of neck and mediastinum.

PMID- 23115421
TI  - Low levels of triiodothyronine in patients with Alzheimer's disease.

PMID- 23115422
TI  - Glucose-6-phosphate Dehydrogenase Deficiency and Pre-eclampsia: Possibility of
      Treatment.

PMID- 23115423
TI  - Assessing the validity of diagnostic tests.

PMID- 23115425
TI  - ELISA Cut-off Point for the Diagnosis of Human Brucellosis; a Comparison with
      Serum Agglutination Test.
AB  - BACKGROUND: Brucellosis is a world-wide disease, which has a diverse clinical
      manifestation, and its diagnosis has to be proven by laboratory data. Serum
      agglutination test (SAT) is the most-widely used test for diagnosing brucellosis.
      The enzyme linked immunosorbent assay (ELISA) can also determine specific
      antibody classes against brucella. It is a sensitive, simple and rapid test,
      which could be an acceptable alternative to SAT with fewer limitations, however,
      like any other new test it should be further evaluated and standardized for
      various populations. This study was planned to determine an optimal cut-off
      point, for ELISA which would offer maximum sensitivity and specificity for the
      test when compared to SAT. METHODS: Four hundred and seven patients with fever
      and other compatible symptoms of brucellosis were enrolled in the study. Serum
      agglutination test, 2-Mercaptoethanol test, and ELISA were performed on their
      sera. RESULTS: The cut-off point of 53 IU/ml of ELISA-IgG yielded the maximal
      sensitivity and specificity comparing to the other levels of ELISA-IgG, and was
      considered the best cut off-point of ELISA-IgG to diagnose acute brucellosis. At
      this cut-off, the sensitivity, specificity, positive predictive value, negative
      predictive value, positive likelihood ratio, and negative likelihood ratio were
      84.09%, 85.38%, 62.20, 94.90, 5.75, 0.18, respectively. CONCLUSION: The best cut
      off point of ELISA-IgG is 53 IU/ml, which yields the maximal sensitivity and
      specificity to diagnose acute brucellosis.

PMID- 23115424
TI  - The role of tumor protein 53 mutations in common human cancers and targeting the
      murine double minute 2-p53 interaction for cancer therapy.
AB  - The gene TP53 (also known as protein 53 or tumor protein 53), encoding
      transcription factor P53, is mutated or deleted in half of human cancers,
      demonstrating the crucial role of P53 in tumor suppression. There are reports of
      nearly 250 independent germ line TP53 mutations in over 100 publications. The P53
      protein has the structure of a transcription factor and, is made up of several
      domains. The main function of P53 is to organize cell defense against cancerous
      transformation. P53 is a potent transcription factor that is activated in
      response to diverse stresses, leading to the induction of cell cycle arrest,
      apoptosis or senescence. The P53 tumor suppressor is negatively regulated in
      cells by the murine double minute 2 (MDM2) protein. Murine double minute 2 favors
      its nuclear export, and stimulates its degradation. Inhibitors of the P53-MDM2
      interaction might be attractive new anticancer agents that could be used to
      activate wild-type P53 in tumors. Down regulation of MDM2 using an small
      interfering RNA (siRNA) approach has recently provided evidence for a new role of
      MDM2 in the P53 response, by modulating the inhibition of the cyclindependent
      kinase 2 (cdk2) by P21/WAF1 (also known as cyclin-dependent kinase inhibitor 1 or
      CDK-interacting protein 1).

PMID- 23115426
TI  - The effects of Adding Meperidine to Heavy Intrathecal Lidocaine on Hemodynamic
      Changes and Blood Loss in Open Prostatectomy: A Randomized Double-Blind Clinical
      Trial.
AB  - BACKGROUND: Clinical investigations have reported several anesthetic properties
      of intrathecal injections of meperidine. The purpose of this study was to
      investigate the effect of adding meperidine to intrathecal heavy lidocaine on
      hemodynamic changes and blood loss in patients undergoing elective suprapubic
      open prostatectomy. METHODS: In a randomized double-blind clinical trial, 77
      patients candidate for elective suprapubic open prostatectomy were allocated to
      two equal groups. All patients in the control and experimental groups received
      heavy lidocaine intrathecally. A low dose of meperidine was added to lidocaine in
      the experiment group. Changes in blood pressure and heart rate were measured and
      documented in several intervals. Blood loss, transfusion rate, shivering, nausea,
      vomiting, need to an analgesic drug, and transient neurologic symptoms were also
      recorded. RESULTS: No significant difference was observed between the two groups
      in regards to blood pressure changes in operating room. Blood pressure increase
      was more prevalent among patients of the control group immediately in post
      operating period. There were significantly (P<0.0001) less post-operative
      bleeding and need to transfusion in the experimental group. CONCLUSION: Adding
      low dose of meperidine to lidocaine induces minimal effect on blood pressure
      change in operating room, but prevent increasing of blood pressure in post
      operative period with a reduction of bleeding. TRIAL REGISTRATION NUMBER:
      IRCT138903061936N2.

PMID- 23115427
TI  - The prediction of physical activity intention and behavior in elderly male
      residents of a nursing home: a comparison of two behavioral theories.
AB  - BACKGROUND: Regular physical activity is ranked as a leading health indicator.
      Despite the extensive benefits of physical activity, elder people are much less
      active than desired. Using Theory of Planned Behavior (TPB) and the self-efficacy
      construct, this study examined the prediction of physical activity intention and
      behavior in a sample of elderly male resident of a nursing home. METHODS: In a
      cross-sectional study of the residents of Kahrizak Nursing Home in Tehran, Iran,
      elderly men who were 60 years or older, capable of independent living, mobility,
      and verbal communication were asked to complete measures of the TPB, self
      efficacy and physical activity behavior. RESULTS: A hierarchical step-wise
      multiple regression analysis indicated that affective/instrumental attitude,
      subjective norm, and perceived behavioral control (PBC) explained 32.8% of the
      variance in physical activity intention, and self-efficacy provided an additional
      2.7%. In a reverse step regression, the TPB variables explained an additional
      12.2% of physical activity intention. In a multiple regression analysis on
      physical activity behavior, affective/instrumental attitude, subjective norm,
      perceived behavioral control (PBC) and intention explained 15.7% of the variance
      in physical activity behavior while self-efficacy contributed an additional 5.6%.
      In the reverse step regression, TPB predictors contributed an additional 3.0% in
      explaining the variance in physical activity behavior. CONCLUSION: The results
      indicate that in addition to the TPB, self-efficacy may also play an important
      role in the prediction of behavior, and should be included in the design of
      physical activity programs for elderly men of nursing home residents.

PMID- 23115428
TI  - Psychometric properties and diagnostic accuracy of the edinburgh postnatal
      depression scale in a sample of Iranian women.
AB  - BACKGROUND: Edinburgh Postnatal Depression Scale (EPDS) has been used as a
      reliable screening tool for postpartum depression in many countries. This study
      aimed to assess the psychometric properties and diagnostic accuracy of the EPDS
      in a sample of Iranian women. METHODS: Using stratified sampling 262 postpartum
      women (2 weeks-3 months after delivery) were selected from urban and rural health
      center in the city of Isfahan. They were interviewed using EPDS and Hamilton
      depression rating scale (HDRS). Data were assessed using factor analysis,
      diagnosis analysis of receiver operating characteristic (ROC) curve, Cronbach's
      alpha and Pearson correlation coefficient. RESULTS: The age of then participants
      ranged 18-45 years (26.6+/-5.1). Based on a cut-off point of >13 for HDRS, 18.3%
      of the participants. The overall reliability (Cronbach's alpha) of EPDS was 0.79.
      There was a significant correlation (r(2)=0.60, P value<0.01) between EPDS and
      HDRS. Two factor analysis showed that anhedonia and depression were two
      explanatory factors. At a cut-off point12 the sensitivity of the questionnaire
      was 78% (95% CI: 73%-83%) and its specificity was 75% (95% CI: 72%-78%).
      CONCLUSION: The Persian version of the EPDS showed appropriate psychometric
      properties diagnostic accuracy index. It can be used by health system
      professionals for detection, assessment and treatment for mothers with post
      partum depression.

PMID- 23115429
TI  - The effects of piper sarmentosum water extract on the expression and activity of
      11beta-hydroxysteroid dehydrogenase type 1 in the bones with excessive
      glucocorticoids.
AB  - BACKGROUND: Long-term glucocorticoid therapy causes secondary osteoporosis
      leading to pathological fractures. Glucocorticoid action in bone is dependant
      upon the activity of 11beta-hydroxysteroid dehydrogenase type 1 enzyme (11beta
      HSD1). Piper sarmentosum is a local herb that possesses the ability to inhibit 11
      betaHSD1 enzyme activity. We aimed to determine the effects of Piper sarmentosum
      water extract on 11-betaHSD1 expressions and activity in the bones of
      glucocorticoid-treated adrenalectomized rats. METHODS: Forty male Sprague-Dawley
      rats (200-250 g) were used. Twenty-four animals were adrenalectomized and
      received intramuscular injection of dexamethasone (120 MUg/kg/day). They were
      simultaneously administered with either Piper sarmentosum water extract (125
      mg/kg/day), GCA (120 mg/kg/day) or distilled water as vehicle by oral gavage for
      two months. Eight animals were sham-operated and given vehicle daily, i.e.
      intramuscular olive oil and oral distilled water. RESULTS: Following two months
      treatment, dexamethasone-treated adrenalectomized rats had significantly lower
      11beta-HSD1 dehydrogenase activity and higher 11beta-HSD1 expression in the
      femoral bones compared to the sham-operated and baseline group. The rats
      supplemented with Piper sarmentosum water extract had significantly higher 11beta
      HSD1 dehydrogenase activity and lower 11beta-HSD1 expression in the bones.
      CONCLUSION: The results showed that Piper sarmentosum water extract had the
      ability to prevent glucocorcoticoid excess in the bones of glucocorticoid-treated
      adrenalectomized rats through the local modulation of 11beta-HSD1 expression and
      activity, and may be used as prophylaxis for osteoporosis in patients on long
      term glucocorticoid treatment.

PMID- 23115430
TI  - HESA-A Exerts Its Cytoprotective Effects through Scavenging of Free Radicals: An
      in Vitro Study.
AB  - BACKGROUND: Natural medicines have been recently considered more reasonable for
      human use most notably due to their safety and tolerance. HESA-A is a marine
      originated herbal medicine with a variety of healing effects. However, its exact
      biological mechanism is not clear. The present study aimed at the evaluation of
      the HESA-A antioxidant effect. METHODS: Chinese hamster ovary (CHO) and human
      embryonic kidney (HEK293T) cells were treated with different concentrations of
      HESA-A and H(2)O(2) followed by cell proliferation assays. The antioxidant effect
      of the HESA-A preparations was evaluated by an antioxidant assay kit. RESULTS:
      The viability of CHO and HEK293T cells were about 89% following their incubation
      with 100 and 200 ng/ml HESA-A, respectively for 1.5 hrs. However, when the cells
      were incubated with concentrations of 300 ng/ml or more, the cell viability
      significantly decreased to 48% compare to the control cells. The cytotoxic
      effects of H(2)O(2) were observed after 2 hrs of incubation of the HEK293T or CHO
      cells with 10 mM or 16 mM H(2)O(2), respectively, while in the presence of HESA-A
      the cytotoxicity was significantly decreased. Antioxidant assay revealed that
      HESA-A scavenges free radicals. CONCLUSION: The findings indicate that HESA-A had
      cytoprotective effects in vitro, and that such an effect might be due to
      antioxidant properties.

PMID- 23115431
TI  - Tilt table practice improved ventilation in a patient with prolonged artificial
      ventilation support in intensive care unit.
AB  - Patients who are on prolonged ventilator support in critical care unit present
      wide variety of complications, which range from reduction in oxygen uptake to
      various musculoskeletal impairments. Early mobilization and rehabilitation are
      encouraged to manage these complications effectively. Use of tilt table to
      motivate early mobilization in the intensive care unit for ventilator practices
      is not a usual practice. However, this new technique has attracted involvements
      of clinicians and therapists for its therapeutic benefits to the patient. Herein
      we describe a case of a seventy eight-year-old male patient who suffered Motor
      car accident, and was on ventilator support in intensive care unit for more than
      one month. He underwent treatment using a tilt table protocol with other routine
      treatment, which benefited him based on clinical as well as physiological
      variables. For practitioners in intensive care units, this report may offer
      perceptivity into the alternate practice of early mobilization using tilt table,
      and for investigators it may promote interest for further studies.

PMID- 23115432
TI  - Thrombolytic therapy for cerebral vein thrombosis in antiphospholipid syndrome
      secondary to systemic lupus erythematosus.
AB  - A 20-year-old woman was admitted to a Gynecology Hospital in her 6(th) month of
      pregnancy for high blood pressure and tonic-clonic seizure. Primary diagnosis was
      eclampsia, and for that reason she underwent cesarean section. She also had
      headache on frontal and parietal areas without nausea or vomiting. There was not
      a focal neurological sign. Rheumatology consultation was requested. Systemic
      lupus erythematosus and secondary antiphospholipid (APS) was confirmed. The
      patient had headache that continued several days after cesarean section,
      therefore, brain magnetic resonance imaging (MRI) and magnetic resonance
      venography (MRV) were performed, and cerebral vein thrombosis was documented.
      Distal segment of right lateral sinus and sigmoid sinus were not appeared in
      brain MRV. Abnormal hypersignal intensity of right lateral sinus/coronal T2 was
      detected. Thrombolytic therapy with 20 mg tissue plasminogen activator on right
      sigmoid and transverse sinus was performed by an interventional neurologist.
      After this procedure, the patient(')s headache healed and she was discharged in a
      good condition.

PMID- 23115433
TI  - Current Status of Publications of Cardiovascular Interventions in Iran; a PubMed
      Based Study.

PMID- 23115434
TI  - An "airy" image.

PMID- 23115435
TI  - Nosocomial infections: the definition criteria.

PMID- 23115437
TI  - Gender differences in the prevalence of electrocardiogram abnormalities in the
      elderly: a population survey in India.
AB  - BACKGROUND: The health transition in India reflects the growing burden of
      cardiovascular diseases. It is well-known that there are significant and
      meaningful differences in the measured electrocardiogram (ECG) parameters between
      females and males. Specific to ECG diagnosis and ischemia, reports have indicated
      a higher number of false positive results in female patients than in male
      patients. This study was aimed at examining gender difference in the prevalence
      of ECG abnormality in older people who were free of coronary heart disease (CHD)
      and its associated risk factors. METHODS: This study was conducted in Solapur
      city using 400 apparently healthy asymptomatic subjects with an age range of 45
      to 74 years. A resting 12-lead ECG was recorded in supine position in accordance
      with classical recommendations. The various ECG abnormalities were defined
      according to Minnesota code. The findings were analyzed using Chi Square test at
      P<0.05. RESULTS: Out of 400 ECGs recorded, 152 showed abnormalities. The
      prevalence of ECG abnormalities was significantly (P<0.001) more in males than in
      females. Major prevalence of ECG abnormalities in males observed were LAD, LVH,
      sinus bradycardia, LBBB and Q/QS patterns. There was no significant gender
      difference in the prevalence of other ECG abnormalities. CONCLUSION: This study
      has outlined the overall prevalence of ECG abnormalities in males as well as in
      females in Solapur city. We found highly significant (P<0.001) increase in the
      prevalence of ECG abnormalities in males as compare to females.

PMID- 23115436
TI  - Recent advances in the treatment of organophosphorous poisonings.
AB  - Organophosphorous compounds have been employed as pesticides and chemical warfare
      nerve agents. Toxicity of organophosphorous compounds is a result of excessive
      cholinergic stimulation through inhibition of acetyl cholinesterase. Clinical
      manifestations include cholinergic syndromes, central nervous system and
      cardiovascular disorders. Organophosphorous pesticide poisonings are common in
      developing worlds including Iran and Sri Lanka. Nerve agents were used during the
      Iraq-Iran war in 1983-1988 and in a terrorist attack in Japan in 1994-1995.
      Following decontamination, depending on the severity of intoxication the
      administration of atropine to counteract muscarinic over-stimulation, and an
      oxime to reactivate acetyl cholinesterase are indicated. Supportive and intensive
      care therapy including diazepam to control convulsions and mechanical respiration
      may be required. Recent investigations have revealed that intravenous infusion of
      sodium bicarbonate to produce mild to moderate alkalinization is effective.
      Gacyclidine; an antiglutamatergic compound, was also proved to be beneficial in
      conjunction with atropine, pralidoxime, and diazepam in nerve agent poisoning.
      Intravenous magnesium sulfate decreased hospitalization duration and improved
      outcomes in patients with organophosphorous poisoning. Bio-scavengers including
      fresh frozen plasma or albumin have recently been suggested as a useful therapy
      through clearing of free organophosphates. Hemofiltration and antioxidants are
      also suggested for organophosphorous poisoning. Recombinant bacterial
      phosphotriesterases and hydrolases that are able to transfer organophosphorous
      degrading enzymes are very promising in delayed treatment of organophosphorous
      poisoning. Recently, encapsulation of drugs or enzymes in nanocarriers has also
      been proposed. Given the signs and symptoms of organophosphorous poisoning,
      health professionals should remain updated about the recent advances in treatment
      of organophosphorous poisoning poisonings.

PMID- 23115438
TI  - Classification of infections in intensive care units: a comparison of current
      definition of hospital-acquired infections and carrier state criterion.
AB  - BACKGROUND: The rate of nosocomial infection appears to depend on whether it is
      calculated using the Center for Disease Control (CDC) or carrier state criteria.
      The objective of this study was to differentiate between primary endogenous (PE),
      secondary endogenous (SE) and exogenous (EX) infections, and to compare this
      classification with CDC criteria for nosocomial infections. METHODS: Children
      hospitalized for more than 72 h at pediatric intensive care unit during 2004-2005
      were enrolled. Children, who had the infection before the admission, and or did
      not develop an infection within the hospitalization were excluded. Surveillance
      samples were sampled on admission, and then twice a week. Diagnostic samples were
      obtained when infection was suspected based on the clinical condition and
      laboratory findings. Infections were evaluated as PE, SE and EX, and their
      incidences were compared with CDC criteria for nosocomial infections. RESULTS:
      One hundred seventy eight patients were enrolled in the study. Forty-four
      patients (24.7%) develop infection. Twenty-seven patients (61.3%) had PE, 10
      patients (22.7%) had SE, and 7 patients (15.9%) had EX infection. Secondary
      endogenous and EX infections are considered as nosocomial, thus 17 patients
      (38.6%) had a nosocomial infection. Thirty-one patients (70.5%) met CDC criteria
      for nosocomial infections. Seventeen patients (55%) were classified as PE, and 14
      patients (45%) as SE or EX infections. CONCLUSION: Seventy percent of infections
      (31 out of 44 patients) met the CDC criteria for nosocomial infections, but only
      39% of infections (17 out of 44 patients) were classified as nosocomial based on
      carrier state classification.

PMID- 23115439
TI  - The value of touch preparation for rapid diagnosis of brain tumors as an
      intraoperative consultation.
AB  - BACKGROUND: The touch preparation technique is an accurate and rapid method, and
      when used as intraoperative consultation examination technique it preserves a
      good amount of tissue for paraffin embedded sections. This study aimed at
      examining the accuracy of the touch preparation technique by comparing its
      diagnosis with that of final pathological diagnosis made by microscopic
      examinations. METHODS: The diagnoses of 139 central nervous system lesions by
      touch preparation technique and paraffin-embedded sections were compared.
      RESULTS: Touch preparation technique diagnosed correctly 118 (84%) of the
      lesions. However, the technique failed to correctly diagnose 12% of the cases.
      The highest rate of accurate diagnosis (100%) was observed in five types out of
      11 types of tumor examined. However, the technique was not able to diagnose
      hydatid cysts correctly. CONCLUSION: The findings indicate that touch preparation
      technique may be useful in diagnosing tumor type during surgical operations.
      Touch preparation technique is very accurate for intraoperative diagnosis.
      However, adequate clinical history, neuroimaging details, and the intraoperative
      impressions of the neurosurgeons, if provided, help the pathologists to improve
      the diagnostic accuracy of the technique.

PMID- 23115440
TI  - A comparison of case-control and case-only designs to investigate gene
      environment interactions using breast cancer data.
AB  - BACKGROUND: The traditional methods of studying the gene-environment interactions
      need a control group. However, the selection of an appropriate control group has
      been associated with problems. Therefore, new methods, such as case-only design,
      have been created to study such interactions. The objective of this study was to
      compare the case-only and case-control designs using data from patients with
      breast cancer. METHODS: The interaction of genetic and environmental factor as
      well as the ratio of control to population odds ratio was calculated for case
      only (300 patients with breast cancer) and case-control (300 cases of breast
      cancer and 300 matched controls) designs. RESULTS: The confidence intervals and 
      2log likelihood in all variables in case-only design was smaller than those in
      the matched case-control design. In case-only design, the standard errors of some
      variables such as age at menarche, the first delivery at the age of 35 yrs and
      more or no delivery, the history of having live birth, use of oral contraception
      pills, breastfeeding history were less than those in the matched case-control
      design. CONCLUSION: The findings indicate that the case-only design is an
      efficient method to investigate the interaction of genetic and environmental
      factors.

PMID- 23115441
TI  - In vitro antibacterial effects of five volatile oil extracts against
      intramacrophage Brucella abortus 544.
AB  - BACKGROUND: Brucellaabortus is a gram-negative facultative intracellular
      bacterium that can cause a highly contagious disease in sheep, goats, cattle and
      one-humped camels. It is responsible for one of the most important zoonosis in
      human. The aim of this study was to evaluate the role of Mentha piperita,
      Origanum majorana, Citrus lemon, Cinnamomum verum and Myristica fragrans
      essential volatile oil extracts on human macrophages infected by B. abortus 544.
      METHODS: Essential volatile oil extracts from M. piperita, O. majorana, C. lemon,
      C. verum and M. fragrans were extracted. Human macrophages were cultured at a
      density of 2*10(5) cells per well in sterile 96-well microtiter plates, and
      infected with B. abortus 544 at a ratio of 1:100 bacteria/cell. Then essential
      volatile oil extracts were added at a concentration of 1%. At specified times;
      cells were washed, lysed with 0.1% Triton, and plated on 2YT agar to determine
      the number of intracellular bacteria. RESULTS: Cinnamomum verum volatile oil at a
      concentration of 1% had the highest antibacterial activity against B. abortus 544
      inside human macrophages. Its inhibitory effect observed from 24 h and continued
      till 144 h after the infection. Moreover, C. verum (0.1%) in combination with 1%
      concentration of M. piperita, O. majorana, C. lemon or M. fragrans volatile oil
      extracts produced a synergistic inhibitory effect against B. abortus 544.
      CONCLUSION: The results indicate that, among the five selected oil extracts, C.
      verum volatile oil applied either separately or in combination with other oil
      extracts had the most effective antimicrobial activity against Brucella.

PMID- 23115442
TI  - The prevalence of human papilloma virus in esophageal squamous cell carcinoma.
AB  - BACKGROUND: Carcinomas of esophagus, mostly squamous cell carcinomas, occur
      throughout the world. There are a number of suspected genetic or environmental
      etiologies. Human papilloma virus (HPV) is said to be a major etiology in areas
      with high incidence of esophageal carcinoma, while it is hardly detectable in low
      incidence regions. This study was designed to evaluate the prevalence of HPV in
      esophageal squamous cell carcinoma (ESCC) cases diagnosed in Pathology
      Department, Medical School, Shiraz University of Medical Sciences. METHODS: DNA
      material for PCR amplification of HPV genome was extracted from formalin-fixed
      paraffin-embedded tissue blocks of 92 cases of ESCC, diagnosed during 20 years
      from 1982 to 2002. Polymerase chain reaction was performed for amplification and
      detection of common HPV and type specific HPV-16 and HPV-18 genomic sequences in
      the presence of positive control (HPV-18 and HPV positive biopsies of uterine
      exocervix) and additional internal controls i.e. beta-globin and cytotoxic T
      lymphocyte antigen 4 (CTLA4). RESULT: Good amplification of positive control and
      internal controls was observed. However, no amplification of HPV genome was
      observed. CONCLUSION: There is no association between HPV infection and the
      development of esophageal squamous cell carcinoma in the cases evaluated.

PMID- 23115443
TI  - A child with intestinal basidiobolomycosis.
AB  - Fungal infections of the gastrointestinal tract are not common in children,
      especially in immunocompetent ones. In this case report we describe a child who
      was presented with abdominal pain and mass, bloody diarrhea and fever. He was
      treated for amebiasis, but due to treatment failure and deterioration of his
      condition, he underwent a laparatomy. Histologic examination of the excised bowel
      in the second look revealed Basidiobolomycosis, a fungus belonging to the order
      Entomophthorales. The signs, symptoms, treatment and diagnosis of the present
      case indicate that fungal infections must be considered not only in
      immunocompromised patients with abdominal pain and mass, but also in apparently
      immunocompetent ones.

PMID- 23115444
TI  - Immunohistochemistery study in a case of nephrogenic adenoma of bladder.
AB  - Nephrogenic adenoma is a rare benign lesion of bladder that may be confused with
      malignant lesions. There is a strong relation with urinary tract irritation and
      intravesicle instrumentations. Nephrogenic adenoma was initially thought to
      originate from urothelial metaplasia; however, no solid proof is available. We
      present a case of 55-year-old lady with urinary problem. Cystocopic examination
      showed a sessile mass, and biopsy revealed circumscribed proliferation of
      tubules, cysts, and papillae that were lined by low cuboidal to columnar
      epithelial cells. Nephrogenic adenoma can be a significant diagnostic pitfall due
      to the presence of certain histological features such as the presence of enlarged
      nuclei with prominent nucleoli. Immunohistochemistery study was strongly positive
      for CK7, P504S, CD10, and EMA, but negative for CK20, PSA, and P63.

PMID- 23115445
TI  - Guide wire j-tip technique for easy exchange of in situ endotracheal tubes.

PMID- 23115446
TI  - Infective causes of stroke in tropical regions.
AB  - Vascular diseases of the brain are the second reason of the death and the first
      cause of morbidity and disability worldwide. In tropical areas stroke has some
      particular features related to the nature of torrid zones. There are some special
      causes of the stroke, mainly infectious, although some of them are non
      infectious. The most important etiologies are malaria, tuberculosis,
      cysticercosis, syphilis, and Chagas' disease. The mean age of the patients with
      stroke in tropical areas seems to be less than that in developed countries, and
      the disease is more prevalent in younger adults. Prevention and/or treatment of
      the classic risk factors as well as factors related to tropical zones are the
      mainstays of controlling the disease. It has to be mentioned that lack of human
      as well as financial resources makes it difficult to control and treat the
      disease properly. Herein, the etiologies and risk factors of the cerebrovascular
      diseases in tropical regions will be reviewd.

PMID- 23115447
TI  - The efficacy and safety of a high dose of vitamin d in mothers with gestational
      diabetes mellitus: a randomized controlled clinical trial.
AB  - BACKGROUND: During pregnancy and lactation outstanding changes occur in mother's
      vitamin D metabolism. This study was carried out to evaluate the efficacy of
      300,000 IU vitamin D given intramuscularly on body status in new cases of
      gestational diabetes mellitus (GDM). METHODS: This is a randomized clinical trial
      with the follow-up period of 3 months. Totally 45 participants were randomly
      divided into intervention group (IG) and control group (CG). The IG received an
      IM injection of 300,000 IU of vitamin D, whereas CG did not. The glycosylated
      hemoglobin A1C (HBA1C), serum 25-OH-D, parathyroid hormone (PTH), serum calcium
      and phosphorus were measured. RESULTS: Forty five patients including 24 with the
      mean age of 30.7+/-6.2 years in the IG and 21 with the mean age of 29.5+/-4.0
      years in the CG participated in the study. The median concentration of serum
      25(OH)D3 in the IG was to 62.10 nmol/l after the intervention, showing an
      increase of around 158%, compared to before intervention (24.25 nmol/l) whereas
      the CG showed a decrease of around 4.5%. Of the patients, 79.2% of IG and 81.9%
      of CG suffered to some degree from vitamin D deficiency. These figures were 4.2%
      and 71.4% for the IG and CG, respectively after the intervention.For the IG, the
      PTH was significantly lower and Ca was significantly higher after the
      intervention. The serum Phosphorus before and after the intervention in each
      group or between the two groups was not significant. CONCLUSIONS: The single
      300,000 IM dose of vitamin D is regarded as an effective and safe to promptly
      improve vitamin D status in GDM. TRIAL REGISTRATION NUMBER: IRCT138902113840N1.

PMID- 23115448
TI  - A comparison of preoperative ondansetron and dexamethasone in the prevention of
      post-tympanoplasty nausea and vomiting.
AB  - BACKGROUND: Nausea and vomiting are common complications of anesthesia and
      surgery. Patients undergoing tympanoplasty are exposed to a higher risk of
      postoperative nausea vomiting (PONV). These complications may alter the results
      of reconstruction and anatomical alignments. Numerous antiemetics have been
      studied to prevent and treat PONV in patients undergoing tympanoplasty. The aim
      of this study was to compare the effect of intravenous ondansetron and
      dexamethasone on post-tympanoplasty PONV. METHODS: In a double-blind randomized
      controlled clinical trial, 219 patients were divided into three groups including
      one receiving ondansetron, one receiving dexamethazone, and one receiving
      distilled water. All patients were subjected to tympanoplasty type I. The
      patients in the first group received ondansetron (4 mg IV), second group received
      oexamethasone (8 mg IV), and third group received distilled water prior to
      induction of anesthesia. Using Bellivelle(')s scoring system, the incidence of
      PONV and its severity during the 24-hour period after surgery were measured and
      compared. RESULTS: There was no significant difference among PONV in the three
      groups in the first two hours after the surgery. However, in 2-8, 8-16 and 16-24
      hours after the surgery the PONV in ondansetron and dexamethasone groups were
      significantly lower than that in the control group. CONCLUSION: Ondansetron and
      dexamethasone were more effective than placebo in controlling PONV after
      tympanoplasty surgeries. Moreover, dexamethasone was more effective than
      ondansetron in preventing PONV. TRIAL REGISTRATION NUMBER: IRCT201106154005N4.

PMID- 23115449
TI  - Protective effect of vitamins e and C on endosulfan-induced reproductive toxicity
      in male rats.
AB  - BACKGROUND: The role of oxidative stress in endosulfan-induced reproductive
      toxicity has been implicated. This study was performed to evaluate the possible
      protective effect of vitamins E and C, against endosulfan-induced reproductive
      toxicity in rats. METHODS: Fifty adult male Sprague-Dawley rats were randomly
      divided into five groups (n=10 each). The groups included a control receiving
      vehicle, a group treated with endosulfan (10 mg/kg/day) alone, and three
      endosulfan-treated group receiving vitamin C (20 mg/kg/day), vitamin E (200
      mg/kg/day), or vitamine C+vitamin E at the same doses. After 10 days of
      treatment, sperm parameters, plasma lactate dehydrogenase (LDH), plasma
      testosterone and malondialdehyde (MDA) levels in the testis were determined.
      RESULTS: Oral administration of endosulfan caused a reduction in the sperm
      motility, viability, daily sperm production (DSP) and increased the number of
      sperm with abnormal chromatin condensation. Endosulfan administration increased
      testis MDA and plasma LDH. Supplementation of vitamin C and vitamin E to
      endosulfan-treated rats reduced the toxic effect of endosulfan on sperm
      parameters and lipid peroxidation in the testis. Vitamin E was more protective
      than vitamin C in reducing the adverse effects of the endosulfan. CONCLUSION: The
      findings data suggest that administration of vitamins C and E ameliorated the
      endosulfan-induced oxidative stress and sperm toxicity in rat. The effect of
      vitamin E in preventing endosulfan-induced sperm toxicity was superior to that of
      vitamin C.

PMID- 23115450
TI  - Antidiabetic effect of hydroalcholic urticadioica leaf extract in male rats with
      fructose-induced insulin resistance.
AB  - BACKGROUND: Urtica dioica has been used as antihypertensive, antihyperlipidemic
      and antidiabetic herbal medicine. The purpose of this study was to study the
      effect of hydroalcoholic extract of Urtica dioica on fructose-induced insulin
      resistance rats. METHODS: Forty male Wistar rats were randomly divided into five
      groups including control, fructose, extract 50, extract 100 and extract 200. The
      control rat received vehicle, the fructose and extract groups received fructose
      10% for eight weeks. The extract groups received single daily injection of
      vehicle, 50, 100 or 200 mg/kg/day for the two weeks. Blood glucose, insulin, last
      fasting insulin resistance index (FIRI), serum triglyceride (TG), low-density
      lipoprotein (LDL), very low-density lipoprotein (VLDL), high-density lipoprotein
      (HDL), alanin trasaminase (AST) and alkaline phosphatase (ALP), leptin and
      LDL/HDL ratio were determined. RESULTS: Compared to control group, daily
      administration of fructose was associated with significant increase in FIRI,
      blood glucose and insulin, significant decrease in lepin, and no significant
      change in TG, HDL, LDL, LDL/HDL ratio, VLDL, ALT, and ALP. The extract
      significantly decreased serum glucose, insulin, LDL and leptin, and LDL/HDL ratio
      and FIRI. It also significantly increased serum TG, VLDL, and AST, but did not
      change serum ALP. CONCLUSION: We suggest that Urtica dioica extract, by
      decreasing serum glucose, and FIRI, may be useful to improve type 2 diabetes
      mellitus. Also, by positive effect on lipid profile and by decreasing effect on
      leptin, it may improve metabolic syndrome.

PMID- 23115451
TI  - Optimal Electroporation Condition for Small Interfering RNA Transfection into MDA
      MB-468 Cell Line.
AB  - BACKGROUND: Electroporation is a valuable tool for small interfering RNA (siRNA)
      delivery into cells because it efficiently transforms a wide variety of cell
      types. Since electroporation condition for each cell type must be determined
      experimentally, this study presents an optimal electroporation strategy to
      reproducibly and efficiently transfect MDA-MB 468 human breast cancer cell with
      siRNA. METHODS: To identify the best condition, the cells were firstly
      electroporated without siRNA and cell viability was determined by trypan blue and
      MTT assays. Then siRNA transfection in the best condition was performed. Western
      blot analysis was used for monitoring successful siRNA transfection. RESULTS: The
      best condition for electroporation of this cell line was 220 volt and 975 uF in
      exponential decay using the Gene Pulser X cell electroporation system. Our data
      demonstrated that by using proper electroporation condition, DNA methyl
      transferase mRNA was silenced by 10 nmol DNMT1 siRNA in MDA-MB 468 cells when
      compared with negative control siRNA electroporation. Analysis of cell viability
      demonstrated that optimal electroporation condition resulted in 74% and 78% cell
      viability by trypan blue staining and MTT assay, respectively. CONCLUSION:
      Transfection of the MDA-MB-468 breast cancer cell line with siRNA in the obtained
      electroporation condition was successful and resulted in effective gene silencing
      and high cellular viability.

PMID- 23115452
TI  - Evaluation of a PCR assay to detect enterococcusfaecalis in blood and determine
      glycopeptides resistance genes: van a and van B.
AB  - BACKGROUND: Bacteremia due to Enterococcus faecalis is usually caused by strains
      resistant to most antibiotics. Effective management of the disease is dependent
      on rapid detection and characterization of the bacteria, and determination its
      sensitivity pattern to antimicrobial drugs. The aim of this study was to
      investigate a more rapid and reliable assay for simultaneous diagnosis of
      enterococcal bacteremia and its sensitivity pattern to antimicrobial drugs.
      METHODS: Several bacterial suspensions with different content of two standard
      strains of Enterococcus faecalis resistant to vancomycin were used for
      inoculation to defibrinated sheep blood samples. PCR and routine assay was
      performed on all blood samples with different bacterial content. RESULTS: Routine
      assay and PCR for all inoculated blood samples with >=5 cfu/ml was positive. Mean
      time for PCR and routine assays was 10 hours and 5 days, respectively.
      CONCLUSION: PCR is a more rapid and sensitive assay for simultaneous detection
      and characterization for Enterococcus faecalis, and determination of its
      sensitivity pattern to vancomycin.

PMID- 23115453
TI  - Introducing new laboratory-developed molecular methods in the clinical
      microbiology laboratories.

PMID- 23115454
TI  - Anterior shoulder dislocation and ipsilateral humeral shaft fracture.
AB  - Simultaneous dislocation of shoulder and humeral shaft fracture is a rare injury,
      and there is no clear protocol for its treatment. Herein we present a case of a
      15-year-old boy, who suffered from a job-related accident and sustained fracture
      of humeral shaft associated with ipsilateral anterior shoulder dislocation and
      fracture of greater tuberosity 15 years ago. He received closed reduction of both
      injuries and coaptation plaster splint for four weeks, followed by Sarmiento
      splint at that time. Fifteen years after the injury, he has no problem related to
      the previous injury, and does not experience any episode of shoulder instability.

PMID- 23115455
TI  - Unruptured middle cerebral artery aneurysm in a patient with systemic lupus
      erthematosus: a diagnostic challenge.
AB  - A 22-year-old female patient presented to the Emergency Department of a tertiary
      care hospital with symptoms of headache and nausea. She has been on a regular
      follow-up for the preceding three and a half years after being diagnosed as
      systemic lupus erythematosus (SLE). She had been treated earlier for SLE
      nephritis in the same institution, and had two relapses of nephrotic syndrome in
      the last three and a half years for which she had been treated and had achieved
      complete remission. All possibilities of headaches in background of SLE were
      considered. CNS examination was inconclusive. There was no nuchal rigidity or no
      cranial nerve deficits. Fundoscopy and Plain CT scan of brain were normal. The
      possibility of CNS-lupus was considered considering the high values of
      antiphospholipid antibodies (APLA). Treatment was initiated accordingly; however,
      there was no improvement in her symptoms. Although being rare in a patient with
      SLE, the possibility of an aneurysm was considered. Four vessel digital
      substraction angiography revealed two unruptured aneurysms of 7.2 mm and 3.9 mm
      in the left middle cerebral artery (MCA) territory. Craniotomy and aneurysmal
      clipping was done successfully, and the patient was relieved of her symptoms. A
      high degree of suspicion towards a rarer cause clinched the diagnosis of a left
      MCA territory stem artery aneurysm. This rationale of strong suspicion and
      discussion of differential diagnosis brought a change in the management of the
      patient.

PMID- 23115456
TI  - Severe Acute Hyperkalemia during Pre-Anhepatic Stage in Cadaveric Orthotopic
      Liver Transplantation.
AB  - A serious hazard to patients during orthotopic liver transplantation is
      hyperkalemia. Although the most frequent and hazardous hyperkalemia occurs
      immediately after reperfusion of the newly transplanted liver, morbid
      hyperkalemia could happen in the other phases during orthotopic liver
      transplantation. However, pre-anhepatic hyperkalemia during orthotopic liver
      transplantation is rare. This report describes one such patient, who without
      transfusion, developed severe hyperkalemia during pre-anhepatic phase. The
      variations in serum potassium concentration of the present case indicate that it
      is necessary to take care of the changes of serum potassium concentration not
      only during reperfusion but also during the other phases of the liver
      transplantation.

PMID- 23115457
TI  - The study of gastric mucosa for possible bacterial causative agent of Crohn's
      disease.

PMID- 23115458
TI  - Mass measles vaccination.

PMID- 23115459
TI  - The authors' reply.

PMID- 23115460
TI  - 'Inattentional blindness': what captures your attention?
AB  - Many mistakes can result from "inattentional blindness."

PMID- 23115461
TI  - 'Gray market' not such a gray area anymore: why hospitals are paying exorbitant
      drug prices.
AB  - Hospitals are paying exorbitant prices for drugs because of an insidious "gray
      market" pipeline.

PMID- 23115463
TI  - Pharmaceutical approval update.
AB  - Truvada for HIV prevention, Xtandi for metastatic castration-resistant prostate
      cancer, and Marqibo, a vincristine liposome injection for acute myelogenous
      leukemia.

PMID- 23115464
TI  - Ticagrelor (brilinta), an antiplatelet drug for acute coronary syndrome.
AB  - Ticagrelor (Brilinta) for acute coronary syndrome.

PMID- 23115466
TI  - State cutbacks to medicaid may hit hospitals hard: new federal reductions might
      compound the stress.
AB  - Hospitals, low-income families, and disabled individuals who rely on Medicaid
      funding will be struggling financially if the government reduces its outlays to
      the states by $800 billion over the next 10 years in order to reduce the federal
      deficit.

PMID- 23115465
TI  - Synthetic cathinones ('bath salts'): legal and health care challenges.
AB  - The growing abuse of toxic stimulants known as "bath salts" can cause psychosis
      and possibly death. Raising awareness of the dangers through patient counseling
      and community outreach programs will be important-especially efforts aimed at
      young people.

PMID- 23115467
TI  - Pregabalin and simvastatin: first report of a case of rhabdomyolysis.
AB  - PURPOSE: We sought to determine whether a case of rhabdomyolysis was a probable
      adverse reaction associated with pregabalin (Lyrica) and simvastatin (Zocor).
      Pregabalin is not recognized as a cause of rhabdomyolysis, but statins are known
      to cause it. PATIENT SUMMARY: A 70-year-old man with a history of fibromyalgia,
      type-2 diabetes, hypercholesterolemia, and chronic back pain presented to the
      emergency department with altered mental status, limb weakness, twitching, and
      slurred speech. He was taking multiple pain and neuropathic medications and had
      recently started taking lisinopril (e.g., Zestril) and simvastatin. His
      pregabalin dose was also increased from 50 mg to 100 mg three times daily. On
      admission, serum creatinine (SCr) and creatine phosphokinase (CPK) levels were
      1.5 mg/dL (normal, 0.7-1.5 mg/dL) and 1,391 units/L (normal, 30-170 units/L),
      respectively. Metformin (Glucophage) was discontinued, and insulin was started.
      He was alert and oriented. The review of symptoms was normal except for leg
      weakness. He had no seizure activity. Simvastatin was discontinued, and the
      patient was aggressively hydrated. The following day, the SCr level was 1.6 mg/dL
      and the CPK level was 14,191 units/L. Pregabalin was then discontinued. The
      rhabdomyolysis resulted from simvastatin and perhaps also pregabalin. The Naranjo
      Causality Algorithm indicates a probable relationship between rhabdomyolysis and
      combined therapy. Three days later, the patient had significantly improved, and
      CPK began to decline. His discharge plan included all prior medications except
      simvastatin and pregabalin. CONCLUSION: It is not well known that pregabalin can
      cause rhabdomyolysis, and there is only one published report on pregabalin
      induced hepatotoxicity. When different therapies are combined, the risk of
      rhabdomyolysis may be increased. The cause of rhabdomyolysis in our patient might
      be related to decreased renal elimination of both pregabalin and simvastatin
      (e.g., renal tubular reabsorption). It is important to be aware of this
      potentially serious and possibly life-threatening reaction especially when
      medication doses are increased or combined with other agents with similar safety
      issues.

PMID- 23115468
TI  - The nanomedicine revolution: part 2: current and future clinical applications.
AB  - Although many nanotherapeutic and nanodiagnostic agents are in use and have the
      potential to improve health care, many barriers have impeded the development and
      availability of these products. Despite these impediments, it is expected that
      nanomaterials will become an integral part of mainstream medicine.

PMID- 23115469
TI  - European society of cardiology congress 2012.
AB  - Topics include antiplatelet drugs for acute coronary syndrome, renal denervation
      for hypertension, contrast-induced nephropathy, "e-cigarettes," and resistant
      hypertension.

PMID- 23115470
TI  - Identifying the cut-point: the transition from acute to chronic musculoskeletal
      pain.

PMID- 23115471
TI  - Basic aspects of musculoskeletal pain: from acute to chronic pain.
AB  - The transition from acute to chronic musculoskeletal pain is not well understood.
      To understand this transition, it is important to know how peripheral and central
      sensitization are manifested and how they can be assessed. A variety of human
      pain biomarkers have been developed to quantify localized and widespread
      musculoskeletal pain. In addition, human surrogate models may be used to induce
      sensitization in otherwise healthy volunteers. Pain can arise from different
      musculoskeletal structures (e.g. muscles, joints, ligaments, or tendons), and
      differentiating the origin of pain from those different structures is a
      challenge. Tissue specific pain biomarkers can be used to tease these different
      aspects. Chronic musculoskeletal pain patients in general show signs of
      local/central sensitization and spread of pain to degrees which correlate to pain
      intensity and duration. From a management perspective, it is therefore highly
      important to reduce pain intensity and try to minimize the duration of pain.

PMID- 23115472
TI  - Whiplash-associated disorder: musculoskeletal pain and related clinical findings.
AB  - The aim of this paper was to review the physical and psychological processes
      associated with whiplash-associated disorders. There is now much scientific data
      available to indicate the presence of disturbed nociceptive processing, stress
      system responses, muscle and motor changes as well as psychological factors in
      both acute and chronic whiplash-associated disorders. Some of these factors seem
      to be associated with the transition from acute to chronic pain and have
      demonstrated prognostic capacity. Further investigation is required to determine
      if these processes can be modified and if modification will lead to improved
      outcomes for this condition. The burden of whiplash injuries, the high rate of
      transition to chronicity, and evidence of limited effects of current management
      on transition rates demand new directions in evaluation and management. The
      understanding of processes underlying this condition is improving and this lays
      the foundation for the development of more effective management approaches.

PMID- 23115473
TI  - Clinical presentation and manual therapy for upper quadrant musculoskeletal
      conditions.
AB  - In recent years, increased knowledge of the pathogenesis of upper quadrant pain
      syndromes has translated to better management strategies. Recent studies have
      demonstrated evidence of peripheral and central sensitization mechanisms in
      different local pain syndromes of the upper quadrant such as idiopathic neck
      pain, lateral epicondylalgia, whiplash-associated disorders, shoulder
      impingement, and carpal tunnel syndrome. Therefore, a treatment-based
      classification approach where subjects receive matched interventions has been
      developed and, it has been found that these patients experience better outcomes
      than those receiving non-matched interventions. There is evidence suggesting that
      the cervical and thoracic spine is involved in upper quadrant pain. Spinal
      manipulation has been found to be effective for patients with elbow pain, neck
      pain, or cervicobrachial pain. Additionally, it is known that spinal manipulative
      therapy exerts neurophysiological effects that can activate pain modulation
      mechanisms. This paper exposes some manual therapies for upper quadrant pain
      syndromes, based on a nociceptive pain rationale for modulating central nervous
      system including trigger point therapy, dry needling, mobilization or
      manipulation, and cognitive pain approaches.

PMID- 23115476
TI  - Letter to the editor.

PMID- 23115474
TI  - Clinical presentation and manual therapy for lower quadrant musculoskeletal
      conditions.
AB  - Chronic lower quadrant injuries constitute a significant percentage of the
      musculoskeletal cases seen by clinicians. While impairments may vary, pain is
      often the factor that compels the patient to seek medical attention. Traumatic
      injury from sport is one cause of progressive chronic joint pain, particularly in
      the lower quarter. Recent studies have demonstrated the presence of peripheral
      and central sensitization mechanisms in different lower quadrant pain syndromes,
      such as lumbar spine related leg pain, osteoarthritis of the knee, and following
      acute injuries such as lateral ankle sprain and anterior cruciate ligament
      rupture. Proper management of lower quarter conditions should include assessment
      of balance and gait as increasing pain and chronicity may lead to altered gait
      patterns and falls. In addition, quantitative sensory testing may provide insight
      into pain mechanisms which affect management and prognosis of musculoskeletal
      conditions. Studies have demonstrated analgesic effects and modulation of spinal
      excitability with use of manual therapy techniques, with clinical outcomes of
      improved gait and functional ability. This paper will discuss the evidence which
      supports the use of manual therapy for lower quarter musculoskeletal dysfunction.

PMID- 23115477
TI  - AAOMPT platform presentations selection.

PMID- 23115479
TI  - Are you Sleeping? Pilot Comparison of Self-Reported and Objective Measures of
      Sleep Quality and Duration in an Inpatient Alcoholism Treatment Program.
AB  - Sleep disturbances are common among alcohol-dependent individuals and can
      increase risk of relapse. The current study compares subjective and objective
      measures of sleep quality and duration and describes the prevalence of baseline
      sleep disturbances in an inpatient population of alcoholics undergoing their
      first week of detoxification. At baseline, the PSQI revealed that 79% of
      participants were above the cutoff score (>=5) for clinically meaningful sleep
      disturbances (mean = 12.57, SD = 4.38). Actigraphy results revealed that average
      sleep efficiency was 75.89%. Sleep efficiency scores were significantly
      correlated with self-reported sleep efficiency (P = 0.04, r = 0.47). Sleep
      duration measured by the actigraphy watches was not significantly correlated with
      self-reported sleep duration (P = 0.65, r = 0.10). Ongoing assessment of sleep
      disturbances may be a valuable tool for informing the development of customized
      sleep interventions in a similar inpatient alcohol treatment sample.

PMID- 23115478
TI  - Knowledge building insights on biomarkers of arsenic toxicity to keratinocytes
      and melanocytes.
AB  - Exposure to inorganic arsenic induces skin cancer and abnormal pigmentation in
      susceptible humans. High-throughput gene transcription assays such as DNA
      microarrays allow for the identification of biological pathways affected by
      arsenic that lead to initiation and progression of skin cancer and abnormal
      pigmentation. The overall purpose of the reported research was to determine
      knowledge building insights on biomarker genes for arsenic toxicity to human
      epidermal cells by integrating a collection of gene lists annotated with
      biological information. The information sets included toxicogenomics gene
      chemical interaction; enzymes encoded in the human genome; enriched biological
      information associated with genes; environmentally relevant gene sequence
      variation; and effects of non-synonymous single nucleotide polymorphisms (SNPs)
      on protein function. Molecular network construction for arsenic upregulated genes
      TNFSF18 (tumor necrosis factor [ligand] superfamily member 18) and IL1R2
      (interleukin 1 Receptor, type 2) revealed subnetwork interconnections to E2F4, an
      oncogenic transcription factor, predominantly expressed at the onset of
      keratinocyte differentiation. Visual analytics integration of gene information
      sources helped identify RAC1, a GTP binding protein, and TFRC, an iron uptake
      protein as prioritized arsenic-perturbed protein targets for biological processes
      leading to skin hyperpigmentation. RAC1 regulates the formation of dendrites that
      transfer melanin from melanocytes to neighboring keratinocytes. Increased
      melanocyte dendricity is correlated with hyperpigmentation. TFRC is a key
      determinant of the amount and location of iron in the epidermis. Aberrant TFRC
      expression could impair cutaneous iron metabolism leading to abnormal
      pigmentation seen in some humans exposed to arsenicals. The reported findings
      contribute to insights on how arsenic could impair the function of genes and
      biological pathways in epidermal cells. Finally, we developed visual analytics
      resources to facilitate further exploration of the information and knowledge
      building insights on arsenic toxicity to human epidermal keratinocytes and
      melanocytes.

PMID- 23115475
TI  - Dry needling - peripheral and central considerations.
AB  - Dry needling is a common treatment technique in orthopedic manual physical
      therapy. Although various dry needling approaches exist, the more common and best
      supported approach targets myofascial trigger points. This article aims to place
      trigger point dry needling within the context of pain sciences. From a pain
      science perspective, trigger points are constant sources of peripheral
      nociceptive input leading to peripheral and central sensitization. Dry needling
      cannot only reverse some aspects of central sensitization, it reduces local and
      referred pain, improves range of motion and muscle activation pattern, and alters
      the chemical environment of trigger points. Trigger point dry needling should be
      based on a thorough understanding of the scientific background of trigger points,
      the differences and similarities between active and latent trigger points, motor
      adaptation, and central sensitize application. Several outcome studies are
      included, as well as comments on dry needling and acupuncture.

PMID- 23115480
TI  - Phenotypes of Peripheral Blood Lymphocytes and Cytokine Expression in
      Polymyositis and Dermatomyositis before Treatment and after Clinical Remission.
AB  - OBJECTIVE: To investigate peripheral blood lymphocyte subpopulations,
      particularly helper T (Th) cells and cytokine expression before and after
      treatment in polymyositis (PM) and dermatomyositis (DM). PATIENTS AND METHODS:
      Ten patients with PM and 15 with DM were enrolled in this study. As a control we
      used 11 age-matched healthy subjects. We analyzed peripheral blood lymphocytes
      using flow cytometry. Serum cytokines were determined by enzyme-linked
      immunosorbent assay. RESULTS: Th2/Th1 and Th2/Th17 ratios were significantly
      higher in both PM and DM than in controls and this Th2-predominancy is marked in
      DM associated with interstitial pneumonia. IL-1beta, IL-6 and TGF-beta were
      significantly higher in both PM and DM and IL-4 showed a significant increase in
      DM when compared to controls. There was no significant correlation between either
      any lymphocyte subpopulations or serum cytokines and clinical severity markers
      such as the manual muscle strength test, serum creatine kinase, and the total CT
      score. Th2/Th17 in both PM and DM, as well as Th2/Th1 in the latter,
      significantly decreased after clinical remission compared with before treatment.
      CONCLUSIONS: Th2-predominancy as shown by the increase in Th2/Th1 and Th2/Th17
      ratios may suggest active disease in PM/DM but does not reflect clinical
      severity.

PMID- 23115481
TI  - Severe toxicity with a generic formulation of zoledronic Acid: a case report.
AB  - Intravenous zoledronic acid (ZOL) is an integral component for the management of
      patients with bone metastases, but can be associated with transient flu-like
      symptoms, which generally occur only with the first infusion and are typically
      manageable with nonprescription analgesics. A 50-year-old woman with a bone
      metastasis secondary to breast cancer received radiation therapy, brand-name ZOL
      (Zometa((r))), and letrozole. During the first 3 cycles of Zometa (4 mg every 3-4
      weeks), no acute adverse events were reported. For the next 2 cycles she was
      switched to generic ZOL and experienced severe toxicity (nausea, vomiting,
      extreme weakness, and incapacitating bone pain) that required hospitalization.
      Toxicity differences between generic ZOL and Zometa led the patient to pay
      additional costs for Zometa, and subsequent Zometa infusions were without
      incident. This is the first case report documenting a clinically significant
      difference between the safety profiles of a generic formulation of ZOL and brand
      name Zometa.

PMID- 23115482
TI  - A De Novo Germline APC Mutation (3927del5) in a Patient with Familial Adenomatous
      Polyposis: Case Report and Literature Review.
AB  - INTRODUCTION: Characterized by the development of hundreds to thousands of
      colonic adenomas, classic familial adenomatous polyposis (FAP) is one of the most
      common hereditary syndromes associated with an increased risk of colorectal
      cancer. Several studies have attempted to correlate specific APC mutations with
      clinical phenotype.6 However, there is considerable variability in the expression
      of specific phenotypes within families and among individuals with identical
      mutations.7 CASE PRESENTATION: A 30 year-old Hispanic female presented to the
      emergency department with a 2-week history of persistent, worsening, left lower
      quadrant abdominal pain. She had no family history of malignancy. Sigmoidoscopy
      revealed innumerable polyps in the rectum and sigmoid colon and a large mass in
      the sigmoid colon. Biopsy of the mass revealed a moderately differentiated
      adenocarcinoma invading the subserosa. Endoscopy revealed innumerable polyps.
      Genetic testing of the patient via southern blot revealed a germline APC mutation
      3927del5, resulting in a premature truncation of the APC protein at amino acid
      position 1312. CONCLUSION: Genetic information has only recently started being
      incorporated into clinical care. More research and randomized clinical trials
      need to be conducted to definitively characterize random mutations. Once these
      mutations are further understood, FAP patients may be able to be risk stratified
      and this may ultimately improve the screening, diagnosis, and treatment of this
      rare condition.

PMID- 23115484
TI  - Thymidine Phosphorylase Gene Expression in Stage III Colorectal Cancer.
AB  - BACKGROUND: The thymidine phosphorylase (TP) enzyme has several tumor-promoting
      functions. The aim of this study was to explore TP gene expression in relation to
      clinical and histopathological data obtained from patients with stage III
      colorectal cancer. METHODS AND RESULTS: TP gene expression was analyzed by real
      time quantitative PCR in tumor and mucosa samples from 254 patients. TP gene
      expression in tumors correlated with lymph node staging, with higher expression
      relating to a higher number of positive nodes and a worse N-stage. Higher TP
      expression was also associated with a worse histological tumor grade. Patients
      with rectal cancer had significantly higher TP expression in mucosa and tumors
      compared with patients having colon cancer. CONCLUSION: Higher intratumoral TP
      expression appears to be related to a worse N stage, and thus, with a worse
      prognosis. TP gene expression measured in a preoperative biopsy could be of
      interest in preoperative staging.

PMID- 23115483
TI  - Clinical management of pain in advanced lung cancer.
AB  - Lung cancer is the most common cancer in the world and pain is its most common
      symptom. Pain can be brought about by several different causes including local
      effects of the tumor, regional or distant spread of the tumor, or from anti
      cancer treatment. Patients with lung cancer experience more symptom distress than
      patients with other types of cancer. Symptoms such as pain may be associated with
      worsening of other symptoms and may affect quality of life. Pain management
      adheres to the principles set out by the World Health Organization's analgesic
      ladder along with adjuvant analgesics. As pain can be caused by multiple factors,
      its treatment requires pharmacological and non-pharmacological measures from a
      multidisciplinary team linked in with specialist palliative pain management. This
      review article examines pain management in lung cancer.

PMID- 23115485
TI  - Trends in sexual health and risk behaviours among adolescent students in British
      Columbia.
AB  - Regular monitoring of trends in sexual health and sexual behaviours among
      adolescents provides strong evidence to guide intervention programs and health
      policies. Using the province-wide, school-based British Columbia (BC) Adolescent
      Health Surveys of 1992, 1998, and 2003, this study documented the trends in
      sexual health and risk behaviours among adolescents in grades 7 to 12 in BC, and
      explored the associations between sexual behaviours and key risk and protective
      factors. From 1992 to 2003, the percentage of youth who had ever had sexual
      intercourse decreased for both males (33.9% to 23.3%) and females (28.6% to
      24.3%) and the percentage who used a condom at last intercourse increased for
      both males (64.4% to 74.9%) and females (52.9% to 64.2%). Among students who had
      ever had sexual intercourse, the percentage who had first intercourse before age
      14 decreased for both sexes. These encouraging results may be related in part to
      concurrent decreases in the prevalence of sexual abuse or forced intercourse
      among both male and female adolescents. Protective factors such as feeling
      connected to family or school were also associated with lower odds of having
      engaged in risky sexual behaviours. These findings emphasize the importance of
      including questions about adolescent sexual health behaviours, risk exposures,
      and protective factors on national and provincial youth health surveys, to
      monitor trends, inform sexual health promotion strategies and policies, and to
      document the effectiveness of population-level interventions to foster sexual
      health among Canadian adolescents.

PMID- 23115486
TI  - Walking the tightrope.

PMID- 23115487
TI  - The plight of paediatric drug therapy.

PMID- 23115488
TI  - Does active surveillance of serious and life-threatening adverse drug reactions
      improve reporting?

PMID- 23115489
TI  - Pharmacokinetics 101.

PMID- 23115490
TI  - Using pharmacogenetics to understand adverse drug reactions in children.

PMID- 23115491
TI  - Improving standards for paediatric clinical trials.

PMID- 23115492
TI  - The proper use of acetaminophen.
AB  - Acetaminophen (N-acetyl-p-aminophenol, paracetamol [APAP])-induced acute liver
      failure is the most common cause of acute liver failure in adults. In children,
      APAP accounts for 25% of all cases of acute liver failure. The high mortality
      rate associated with this preventable condition makes it vital that
      paediatricians are aware of the potential adverse effects associated with this
      widely used drug. While APAP is generally considered to be safe when used as
      directed, its inclusion in multiple over-the-counter medications, as well as in
      prescription drugs, mandates that physicians promote and educate the general
      public about the proper use of acetaminophen in children.

PMID- 23115493
TI  - Antidepressant use in children and adolescents: Practice touch points to guide
      paediatricians.
AB  - Depression in children and youth is common, and requires an understanding of its
      developmental character and associated comorbid conditions. Initial treatment of
      mild depression involves active supportive measures with a focus on symptom
      reduction and improved daily function. Where pharmacotherapy is warranted,
      evidence supports the use of selective serotonin reuptake inhibitor (SSRI)
      antidepressants, particularly fluoxetine, to manage moderate/severe depression.
      SSRI treatment should include a comprehensive management plan in the context of
      interdisciplinary care, an understanding of its pharmacology and clearly
      articulated goals for symptom reduction, functional status tracking (school, home
      and peers) and monitoring for the emergence of suicidal ideation/behaviour. For
      children with more severe symptoms or complicating factors (comorbid conditions),
      referral to mental health clinicians should be considered. Use of an SSRI should
      be associated with family/patient education about medication effects, specific
      social and health goals that promote self-esteem, improved function and close
      monitoring for adverse effects.

PMID- 23115494
TI  - Drug-induced esophageal injury with an occult vascular ring.
AB  - Drug-induced esophageal injury is an under-recognized clinical problem, and is
      associated with antibiotic use in more than 50% of cases. The current report
      describes a teenage girl who presented with symptoms of pill-induced esophagitis
      following doxycycline use. Subsequent investigations identified a previously
      undiagnosed vascular ring. Although most patients who experience drug-induced
      esophageal injury have no underlying anatomical or functional disorder of the
      esophagus, the condition is more common in areas of esophageal narrowing. The
      present case illustrates the possibility of an occult esophageal obstruction
      representing a risk factor for pill esophagitis. The etiologies, mechanisms and
      management of drug-induced esophageal injury are reviewed, and aspects of
      vascular rings that are relevant to paediatricians are discussed.

PMID- 23115495
TI  - Case 1: A newborn in distress.

PMID- 23115496
TI  - Case 2: Dropping platelet counts in the neonatal intensive care unit - an
      unsuspected cause for thrombocytopenia in a neonate.

PMID- 23115497
TI  - Drug research and treatment for children in Canada: A challenge.
AB  - Historically, children have been 'therapeutic orphans'. Many drugs have not been
      studied or labelled for use in children and adolescents, making the development
      and definition of optimally safe and effective drug therapies for the paediatric
      age group an ongoing challenge. Over the past decade, networks have developed in
      the United States and Europe to enhance drug research for this group, while no
      comparable evolution has occurred in Canada. The present statement provides
      context for the Canadian situation and makes recommendations that address two
      pressing needs: for more drug research focused on Canadian children and
      adolescents, including dedicated support for such research; and for increasing
      human capacity to undertake targeted studies. These initiatives should be
      undertaken collaboratively, nationally and internationally, and include
      strategic, innovative approaches to the unique problems and ethical issues posed
      by drug research in this population.

PMID- 23115498
TI  - Selective serotonin reuptake inhibitors in pregnancy and infant outcomes.
AB  - Adequate treatment of depression during pregnancy is very important for maternal,
      fetal and neonatal health. Selective serotonin reuptake inhibitors (SSRIs) are
      commonly used antidepressants. According to one American study, approximately 7%
      of pregnant women were prescribed an SSRI in 2004-2005. First trimester use of
      SSRIs, as a group, is unlikely to increase the risk of congenital malformations.
      Paroxetine may be associated with a small increased risk of cardiac
      malformations, but evidence remains inconclusive. Fetal exposure to SSRIs closer
      to time of birth may result in respiratory, motor, central nervous system and
      gastrointestinal symptoms in about 10% to 30% of newborns (SSRI neonatal
      behaviour syndrome). These symptoms are usually mild and transient. Persistent
      pulmonary hypertension of the newborn is an extremely rare consequence of fetal
      exposure. This information should be used to make individual risk-benefit
      decisions when considering the treatment of depression during pregnancy. Newborns
      with late-pregnancy exposure to SSRIs should be observed in hospital for at least
      48 h.

PMID- 23115499
TI  - Treating cough and cold: Guidance for caregivers of children and youth.
AB  - Despite the widespread use of over-the-counter (OTC) cough and cold medications
      (CCMs), the effectiveness of most CCMs has not been proven in children. A meta
      analysis summarizing trials using OTC CCMs for viral-induced cough found no
      evidence for or against the use of OTC medicines in both paediatric and adult
      populations when cough frequency and severity, as well as physician assessments,
      were compared. Furthermore, North American data suggest that OTC CCMs may be
      associated with medication errors and adverse events, resulting in visits to
      emergency departments and even leading to death. The present article provides
      information on current evidence for cough and cold therapies, including fluid
      intake, humidified air, antihistamines, echinacea, zinc, honey and vitamin C, for
      caregivers of children and youth.

PMID- 23115500
TI  - Influenza vaccine recommendations for children and youth for the 2011/2012
      season.

PMID- 23115501
TI  - Management recommendations for metabolic complications associated with second
      generation antipsychotic use in children and youth.
AB  - BACKGROUND: Second-generation antipsychotics are commonly associated with
      metabolic complications. These medications are being used more frequently for the
      treatment of mental health disorders in children, which has stimulated the need
      for creating formal guidelines on monitoring their safety and effectiveness.
      Previous guidelines have been developed for monitoring metabolic and neurological
      complications. To assist practitioners who perform these monitoring procedures, a
      complementary set of treatment recommendations have been created for situations
      in which abnormal measurements or results are encountered. OBJECTIVE: To create
      evidence-based recommendations to assist in managing metabolic complications in
      children being treated with second-generation antipsychotics. METHODS: A
      systematic review of the literature on metabolic complications of second
      generation antipsychotic medications in children was conducted. Members of the
      consensus group evaluated the information gathered from the systematic review of
      the literature and used a nominal group process to reach a consensus on treatment
      recommendations. Wherever possible, references were made to existing guidelines
      on the evaluation and treatment of metabolic abnormalities in children. RESULTS:
      Evidence-based recommendations are presented to assist in managing metabolic
      complications including weight gain; increased waist circumference; elevation in
      prolactin, cholesterol, triglyceride and glucose levels; abnormal liver function
      tests and abnormal thyroid studies. CONCLUSION: The use of second-generation
      antipsychotics requires proper monitoring procedures. The present treatment
      guideline provides guidance to clinicians on the clinical management of metabolic
      complications if they occur.

PMID- 23115502
TI  - Evidence-based recommendations for monitoring safety of second-generation
      antipsychotics in children and youth.
AB  - BACKGROUND: The use of antipsychotics, especially second-generation
      antipsychotics (SGAs), for children with mental health disorders in Canada has
      increased dramatically over the past five years. These medications have the
      potential to cause major metabolic and neurological complications with chronic
      use. OBJECTIVE: To synthesize the evidence for specific metabolic and
      neurological side effects associated with the use of SGAs in children, and
      provide evidence-based recommendations for the monitoring of these side effects.
      METHODS: A systematic review of controlled clinical trials of SGAs involving
      children was performed. Recommendations for monitoring SGA safety were made
      according to a classification scheme based on the GRADE (Grading of
      Recommendations Assessment, Development and Evaluation) system. When there was
      inadequate evidence, recommendations were based on consensus and expert opinion.
      A multidisciplinary consensus group reviewed all relevant evidence and reached
      consensus on the recommendations. RESULTS: The present guidelines provide
      evidence-based recommendations for monitoring SGA safety. The strength of
      recommendations for specific physical examination manoeuvres and laboratory tests
      are provided for each SGA medication at specific time points. CONCLUSION:
      Multiple randomized controlled trials evaluated the efficacy of many of the SGAs
      in paediatric mental health disorders. These benefits, however, are not without
      risks - both metabolic and neurological side effects occur in children treated
      with SGAs. The risk of weight gain, increased body mass index and abnormal lipid
      levels is greatest with olanzapine, followed by clozapine and quetiapine. The
      risk of neurological side effects of the treatment is greatest with risperidone,
      olanzapine and aripiprazole. Appropriate monitoring procedures for adverse
      effects will improve the quality of care of children treated with these
      medications.

PMID- 23115503
TI  - Treatment recommendations for extrapyramidal side effects associated with second
      generation antipsychotic use in children and youth.
AB  - BACKGROUND/OBJECTIVE: Antipsychotic use in children is increasing. The purpose of
      the present article was to provide guidance to clinicians on the clinical
      management of extrapyramidal side effects of second-generation antipsychotics.
      METHODS: Published literature, key informant interviews, and discussions with
      panel members and stakeholder partners were used to identify key clinical areas
      of guidance and preferences on format for the present recommendations. Draft
      recommendations were presented to a guideline panel. Members of the guideline
      panel evaluated the information gathered from the systematic review of the
      literature and used a nominal group process to reach a consensus on treatment
      recommendations. A description of the neurological abnormalities commonly seen
      with antipsychotic medications is provided, as well as recommendations on how to
      examine and quantify these abnormalities. A stepwise approach to the management
      of neurological abnormalities is provided. RESULTS: Several different types of
      extrapyramidal symptoms can be seen secondary to antipsychotic use in children
      including neuroleptic-induced acute dystonia, neuroleptic-induced akathisia,
      neuroleptic-induced parkinsonism, neuroleptic-induced tardive dyskinesia, tardive
      dystonia and tardive akathisia, and withdrawal dyskinesias. The overwhelming
      majority of evidence on the treatment of antipsychotic-induced movement disorders
      comes from adult patients with schizophrenia. Given the scarcity of paediatric
      data, recommendations were made with reference to both the adult and paediatric
      literature. Given the limitations in the generalizability of data from adult
      subjects to children, these recommendations should be considered on the basis of
      expert opinion, rather than evidence based. CONCLUSION: Clinicians must be aware
      of the potential of second-generation antipsychotics to induce neurological side
      effects, and should exercise a high degree of vigilance when prescribing these
      medications.

PMID- 23115504
TI  - Does the use of glycerin laxatives decrease feeding intolerance in preterm
      infants?
AB  - BACKGROUND: Glycerin laxatives are often prescribed in the neonatal population
      for meconium evacuation and to promote enteral feeding. However, the literature
      regarding their effectiveness has not been systematically reviewed. OBJECTIVE: To
      assess the effectiveness of glycerin enema or suppository in preventing feeding
      intolerance in preterm infants at <=32 weeks' gestational age or weighing <=1500
      g at birth. METHODS: The Medline, Embase, Cochrane Library, Scopus and Web of
      Science databases were searched to identify studies that evaluated glycerin
      enemas/suppositories for feeding intolerance. Using the Evidence Evaluation
      Worksheet adapted from the American Heart Association's International Liaison
      Committee on Resuscitation, eligible studies were scored for quality, level of
      evidence and direction of support. RESULTS: Two clinical studies that evaluated
      meconium evacuation and feeding intolerance were included. One study showed no
      difference in the time to complete meconium evacuation or establishment of full
      enteral feeds, while the other showed that the times to first meconium passage
      and full enteral feeding were significantly shorter, and the rate of sepsis was
      lower in the glycerin enema group. CONCLUSION: The evidence regarding the
      effectiveness of glycerin laxatives for improving feeding tolerance is
      inconclusive in infants at <=32 weeks' gestational age or weighing <=1500 g at
      birth.

PMID- 23115505
TI  - Three new records of lichen genera opegrapha and phaeographis from the republic
      of Korea.
AB  - This paper provides a description of Opegrapha herbarum, Opegrapha viridis and
      Phaeographis subdividens, all newly identified in the Republic of Korea. The
      characteristic features of O. herbarum include Varia-type asci, Subelevata-type
      ascospores, a lack of secondary metabolites and a saxicolous habitat. O. viridis
      possesses Calcarea-type asci, Vulgata-type ascospores and no chemicals in the
      thallus. P. subdividens is recognizable by its curved to sinuous lirellae,
      divergent labia, a brown and uniformly thick proper exciple which is open at its
      base, 3~4-septate ascospores, and lack of secondary metabolites. All three taxa
      are now reported to exist on Bogil Island in the Republic of Korea.

PMID- 23115506
TI  - Diversity of Culturable Soil Micro-fungi along Altitudinal Gradients of Eastern
      Himalayas.
AB  - Very few studies have addressed the phylogenetic diversity of fungi from
      Northeast India under the Eastern Himalayan range. In the present study, an
      attempt has been made to study the phylogenetic diversity of culturable soil
      fungi along the altitudinal gradients of eastern Himalayas. Soil samples from 24
      m above sea level to 2,000 m above sea level altitudes of North-East India were
      collected to investigate soil micro-fungal community structure and diversity.
      Molecular characterization of the isolates was done by PCR amplification of 18S
      rDNA using universal primers. Phylogenetic analysis using BLAST revealed
      variation in the distribution and richness of different fungal biodiversity over
      a wide range of altitudes. A total of 107 isolates were characterized belonging
      to the phyla Ascomycota and Zygomycota, corresponding to seven orders
      (Eurotiales, Hypocreales, Calosphaeriales, Capnodiales, Pleosporales, Mucorales,
      and Mortierellales) and Incertae sedis. The characterized isolates were analysed
      for richness, evenness and diversity indices. Fungal diversity had significant
      correlation with soil physico-chemical parameters and the altitude. Eurotiales
      and Hypocreales were most diverse and abundant group of fungi along the entire
      altitudinal stretch. Species of Penicillium (D = 1.44) and Aspergillus (D =
      1.288) were found to have highest diversity index followed by Talaromyces (D =
      1.26) and Fusarium (D = 1.26). Fungal distribution showed negative correlation
      with altitude and soil moisture content. Soil temperature, pH, humidity and
      ambient temperature showed positive correlation with fungal distribution.

PMID- 23115507
TI  - Notes on species of the lichen genus canoparmelia elix & hale in South Korea.
AB  - Detailed descriptions of five species of the lichen genus Canoparmelia Elix &
      Hale. are presented. Until now, three species of the genus Canoparmelia,
      including C. apata (Krempelh.) Elix & Hale, C. owariensis (Asah.) Elix, and C.
      texana (Tuck.) Elix & Hale have been reported in South Korea. Canoparmelia
      carneopruinata (Zahlbr.) Elix & Hale, C. crozalsiana (de Lesd.) Elix & Hale, and
      C. ecaperata (Mull. Arg.) Elix & Hale are new to the South Korean lichen flora.
      An artificial key is provided for all species of Canoparmelia, including the
      three new records.

PMID- 23115508
TI  - Effects of Aeration of Sawdust Cultivation Bags on Hyphal Growth of Lentinula
      edodes.
AB  - The effects of aeration through lid filters on the hyphal growth of Lentinula
      edodes (oak mushroom) in sawdust cultivation bags were investigated. The aeration
      treatment levels were traditional 27 mm hole cotton plugs, cotton balls and
      combinations of seven hole sizes * two hole positions (up and under) in the lids
      covering plastic bags containing 1.4 kg sawdust medium at 63% moisture that had
      been autoclaved for one hour and inoculated with sawdust spawn of L. edodes
      strain 921. Aeration treatment effects were measured based on the CO(2)
      concentration at the 15th wk, as well as the hyphal growth rate and degree of
      weight loss of bags every 14 days for 15 wk. In bags with traditional cotton
      plugs, the CO(2) concentration was 3.8 +/- 1.3%, daily mean hyphal growth was 2.3
      +/- 0.6 mm and daily mean weight loss was 0.84 +/- 0.26 g. In the bags with 15 mm
      diameter holes, the CO(2) concentration was 6.0 +/- 1.6%, daily hyphal growth was
      2.8 +/- 0.2 mm and daily weight loss was 0.86 +/- 0.4 g. The bags with 15 mm
      holes had a higher CO(2) concentration and lower water loss than bags with other
      hole sizes, but the hyphal growth was not significantly different from that of
      other bags. The weight loss of bags increased proportionally relative to the lid
      hole sizes. Taken together, these results indicate that traditional cotton plugs
      are economically efficient, but 15 mm hole lids are the most efficient at
      maintaining hyphal growth and controlling water loss while allowing CO(2)
      emissions.

PMID- 23115509
TI  - Effect of Soil Ameliorators on Ectomycorrhizal Fungal Communities that Colonize
      Seedlings of Pinus densiflora in Abandoned Coal Mine Spoils.
AB  - In this study, the effect of soil ameliorators on ectomycorrhizal (ECM) fungal
      communities in coal mine spoils was investigated. Organic fertilizers and slaked
      lime were applied as soil ameliorators in 3 abandoned coal mine spoils. One year
      after the initial treatment, roots of Pinus densiflora seedlings were collected
      and the number of ECM species, colonization rate, and species diversity were
      assessed. The results showed that the soil ameliorators significantly increased
      ECM colonization on the roots of P. densiflora. The results suggest that soil
      ameliorators can have a positive effect on ECM fungi in terms of growth of host
      plants and show the potential use of soil ameliorator treatment for revegetation
      with ECM-colonized pine seedlings in the coal mine spoils.

PMID- 23115510
TI  - Biochemical Characterization of an Extracellular beta-Glucosidase from the
      Fungus, Penicillium italicum, Isolated from Rotten Citrus Peel.
AB  - A beta-glucosidase from Penicillium italicum was purified with a specific
      activity of 61.8 U/mg, using a chromatography system. The native form of the
      enzyme was an 88.5-kDa tetramer with a molecular mass of 354 kDa. Optimum
      activity was observed at pH 4.5 and 60C, and the half-lives were 1,737, 330, 34,
      and 1 hr at 50, 55, 60, and 65C, respectively. Its activity was inhibited by 47%
      by 5 mM Ni(2+). The enzyme exhibited hydrolytic activity for p-nitrophenyl-beta-D
      glucopyranoside (pNP-Glu), p-nitrophenyl-beta-D-cellobioside, p-nitrophenyl-beta
      D-xyloside, and cellobiose, however, no activity was observed for p-nitrophenyl
      beta-D-lactopyranoside, p-nitrophenyl-beta-D-galactopyranoside, carboxymetyl
      cellulose, xylan, and cellulose, indicating that the enzyme was a beta
      glucosidase. The k(cat)/K(m) (s(-1) mM(-1)) values for pNP-Glu and cellobiose
      were 15,770.4 mM and 6,361.4 mM, respectively. These values were the highest
      reported for beta-glucosidases. Non-competitive inhibition of the enzyme by both
      glucose (K(i) = 8.9 mM) and glucono-delta-lactone (K(i) = 11.3 mM) was observed
      when pNP-Glu was used as the substrate. This is the first report of non
      competitive inhibition of beta-glucosidase by glucose and glucono-delta-lactone.

PMID- 23115511
TI  - Immunomodulating and Antitumor Activities of Panellus serotinus Polysaccharides.
AB  - This study was initiated in order to investigate the anticancer and
      immunomodulating activities of crude polysaccharides extracted in methanol,
      neutral saline, and hot water (hereinafter referred to as Fr. MeOH, Fr. NaCl, and
      Fr. HW, respectively) from the fruiting bodies of Panellus serotinus. Content of
      beta-glucan and protein in Fr. MeOH, Fr. NaCl, and Fr. HW extracts of P.
      serotinus ranged from 22.92~28.52 g/100 g and 3.24~3.68 g/100 g, respectively. In
      vitro cytotoxicity tests, none of the various fractions of crude polysaccharides
      were cytotoxic against sarcoma 180, HT-29, NIH3T3, and RAW 264.7 cell lines at
      the tested concentration. Intraperitoneal injection with crude polysaccharides
      resulted in a life prolongation effect of 23.53~44.71% in mice previously
      inoculated with sarcoma 180. Treatment with Fr. HW resulted in an increase in the
      numbers of spleen cells by 1.3 fold at the concentration of 50 ug/mL compared
      with control. Treatment with Fr. NaCl resulted in improvement of the immuno
      potentiating activity of B lymphocytes by increasing the alkaline phosphatase
      activity by 1.4 fold, compared with control, at the concentration of 200 ug/mL.
      Among the three fractions, maximum nitric oxide (13.48 uM) was recorded at 500
      ug/mL in Fr. HW. Production of tumor necrosis factor alpha, interleukin-1beta,
      and interleukin-6 was significantly higher, compared to the positive control,
      concanavalin A, at the tested concentration. Therefore, treatment with crude
      polysaccharides extracted from the fruiting body of P. serotinus could result in
      improvement of antitumor activity.

PMID- 23115512
TI  - Characterization of Species of Cladobotryum which Cause Cobweb Disease in Edible
      Mushrooms Grown in Korea.
AB  - Four Cladobotryum isolates were collected from four different commercially grown
      mushroom types infected with cobweb disease in Cheongdo-gun and Chilgok-gun of
      Gyeongbuk Province, Korea in 2010. The isolates were identified as C. mycophilum
      from Agaricus bisporus and Pleurotus eryngii, C. varium from Flammulina velutipes
      and Hypsizygus marmoreus. The cultural characteristics of the four isolates were
      investigated using potato dextrose agar (PDA) media under nine different
      temperatures ranging from 5~32C. Rapid growth of the isolates to colony diameters
      of 47~82 mm was observed at conditions of 18~22C. No growth was observed at 32C.
      C. mycophilum produced a yellowish red pigment while C. varium produced a cream
      colored pigment after cultivation for 25 days on PDA. Phylogenetic analysis of
      the internal transcribed spacer region and partial 28S rDNA from the four
      isolates confirmed they were C. mycophilum and C. varium. Cross pathogenicity
      tests revealed that the two isolates of C. mycophilum were highly pathogenic
      toward three mushroom types, but not toward H. marmoreus. The two isolates of C.
      varium were less pathogenic than those of C. mycophilum, but were pathogenic
      toward all mushroom types evaluated.

PMID- 23115513
TI  - Four unrecorded wood decay fungi from seoul in Korea.
AB  - During the investigation of Korean indigenous fungi from Seoul, three genera
      Fuscoporia, Porostereum, and Trametopsis, and four species-Fuscoporia senex,
      Phlebia acerina, Porostereum spadiceum, and Trametopsis cervina were found. Their
      morphological characteristics were examined and their identification was
      confirmed by molecular analysis based on internal transcribed spacer (ITS) and
      nuclear large subunit ribosomal DNA region sequences. These fungi are new to
      Korea and registered here with descriptions.

PMID- 23115514
TI  - First Report of the Lichen Species, Heterodermia flabellata (Fee) D. D. Awasthi,
      and Updated Taxonomic Key of Heterodermia in South Korea.
AB  - Heterodermia flabellata (Fee) D. D. Awasthi was found as a new lichen record in
      Jeju Island of South Korea in 2012. A detailed taxonomic description and comments
      are provided for the taxa. An updated key for all recorded species of
      Heterodermia from South Korea is given.

PMID- 23115515
TI  - Seed-borne Brachycladium penicillatum Intercepted under Plant Quarantine
      Inspection in Korea.
AB  - A fungus detected from the importing seeds of Papaver rhoeas under plant
      quarantine inspection in Korea was identified as Brachycladium penicillatum
      Corda. It differed in morphological characteristics from a similar species, B.
      papaveris, which was known to form no macroconidiophores and no microsclerotia.
      Since the first interception in 2006, this fungus has frequently been found from
      importing seeds of Papaver spp. It was detected from 31 out of 282 seed
      consignments imported from 2006 to 2011. To prevent its introduction to Korea,
      the seed consignments infested by B. penicillatum were destroyed or reshipped.

PMID- 23115516
TI  - Isolation and Characterization of the mheA (Most Highly Expressed) Gene of
      Aspergillus oryzae.
AB  - The amino acid sequence of the mheA gene of Aspergillus oryzae encodes a putative
      metallothionein-like protein 1. The size of the mheA transcript was 497 nt and
      the mheA promoter was induced by glucose, consistent with results of analysis by
      Northern hybridization and with the pdcA promoter, respectively.

PMID- 23115517
TI  - Occurrence of sooty blotch and flyspeck disease on sweet persimmon in Korea.
AB  - Sooty blotch and flyspeck (SBFS), a disease caused by a complex of fungi, results
      in substantial economic losses for commercial growers of sweet persimmon
      (Diospyros kaki L.) in Korea. However, many species causing SBFS in Korea have
      not been identified and sources of inoculum are uncertain. Based on mycological
      characteristics, pathogenicity, and molecular data, the causal fungi were
      identified as Dissoconium sp. and Zygophiala wisconsinensis. This is the first
      report of SBFS of sweet persimmon in Korea.

PMID- 23115518
TI  - Soft Rot of Rhizopus oryzae as a Postharvest Pathogen of Banana Fruit in Korea.
AB  - Soft rot on banana fruit caused by Rhizopus oryzae was identified for the first
      time in Korea. Colonies were white to light brown and formed numerous
      sporangiospores. Optimum temperature for mycelial growth was 30C. Sporangia were
      globose and 30~200 um. Sporangiophores were usually straight, 8~20 um, and
      rhizoids usually in groups of 3~5. Columella were globose to sub-globose and
      90~110 um. Sporangiospores were sub-globose or oval and 4~10 um. Based on its
      mycological characteristics, molecular analysis, and pathogenicity to host
      plants, this fungus was identified as Rhizopus oryzae Went & Prisen Geerligs.
      This is the first report of soft rot on banana caused by Rhizopus oryzae in
      Korea.

PMID- 23115519
TI  - Genetics dissection of complex traits in the genomic era.

PMID- 23115520
TI  - Application of genomic tools in plant breeding.
AB  - Plant breeding has been very successful in developing improved varieties using
      conventional tools and methodologies. Nowadays, the availability of genomic tools
      and resources is leading to a new revolution of plant breeding, as they
      facilitate the study of the genotype and its relationship with the phenotype, in
      particular for complex traits. Next Generation Sequencing (NGS) technologies are
      allowing the mass sequencing of genomes and transcriptomes, which is producing a
      vast array of genomic information. The analysis of NGS data by means of
      bioinformatics developments allows discovering new genes and regulatory sequences
      and their positions, and makes available large collections of molecular markers.
      Genome-wide expression studies provide breeders with an understanding of the
      molecular basis of complex traits. Genomic approaches include TILLING and
      EcoTILLING, which make possible to screen mutant and germplasm collections for
      allelic variants in target genes. Re-sequencing of genomes is very useful for the
      genome-wide discovery of markers amenable for high-throughput genotyping
      platforms, like SSRs and SNPs, or the construction of high density genetic maps.
      All these tools and resources facilitate studying the genetic diversity, which is
      important for germplasm management, enhancement and use. Also, they allow the
      identification of markers linked to genes and QTLs, using a diversity of
      techniques like bulked segregant analysis (BSA), fine genetic mapping, or
      association mapping. These new markers are used for marker assisted selection,
      including marker assisted backcross selection, 'breeding by design', or new
      strategies, like genomic selection. In conclusion, advances in genomics are
      providing breeders with new tools and methodologies that allow a great leap
      forward in plant breeding, including the 'superdomestication' of crops and the
      genetic dissection and breeding for complex traits.

PMID- 23115521
TI  - Quantitative genetics in the genomics era.
AB  - The genetic analysis of quantitative or complex traits has been based mainly on
      statistical quantities such as genetic variances and heritability. These analyses
      continue to be developed, for example in studies of natural populations. Genomic
      methods are having an impact on progress and prospects. Actual relationships of
      individuals can be estimated enabling novel quantitative analyses. Increasing
      precision of linkage mapping is feasible with dense marker panels and designed
      stocks allowing multiple generations of recombination, and large SNP panels
      enable the use of genome wide association analysis utilising historical
      recombination. Whilst such analyses are identifying many loci for disease genes
      and traits such as height, typically each individually contributes a small amount
      of the variation. Only by fitting all SNPs without regard to significance can a
      high proportion be accounted for, so a classical polygenic model with near
      infinitesimally small effects remains a useful one. Theory indicates that a high
      proportion of variants will have low minor allele frequency, making detection
      difficult. Genomic selection, based on simultaneously fitting very dense markers
      and incorporating these with phenotypic data in breeding value prediction is
      revolutionising breeding programmes in agriculture and has a major potential role
      in human disease prediction.

PMID- 23115522
TI  - Application of genomics tools to animal breeding.
AB  - The main goal in animal breeding is to select individuals that have high breeding
      values for traits of interest as parents to produce the next generation and to do
      so as quickly as possible. To date, most programs rely on statistical analysis of
      large data bases with phenotypes on breeding populations by linear mixed model
      methodology to estimate breeding values on selection candidates. However, there
      is a long history of research on the use of genetic markers to identify
      quantitative trait loci and their use in marker-assisted selection but with
      limited implementation in practical breeding programs. The advent of high-density
      SNP genotyping, combined with novel statistical methods for the use of this data
      to estimate breeding values, has resulted in the recent extensive application of
      genomic or whole-genome selection in dairy cattle and research to implement
      genomic selection in other livestock species is underway. The high-density SNP
      data also provides opportunities to detect QTL and to encover the genetic
      architecture of quantitative traits, in terms of the distribution of the size of
      genetic effects that contribute to trait differences in a population. Results
      show that this genetic architecture differs between traits but that for most
      traits, over 50% of the genetic variation resides in genomic regions with small
      effects that are of the order of magnitude that is expected under a highly
      polygenic model of inheritance.

PMID- 23115523
TI  - Human complex trait genetics: lifting the lid of the genomics toolbox - from
      pathways to prediction.
AB  - During the initial stages of the genome revolution human genetics was hugely
      successful in discovering the underlying genes for monogenic diseases. Over 3,000
      monogenic diseases have been discovered with simple patterns of inheritance. The
      unravelling and identification of the genetic variants underlying complex or
      multifactorial traits, however, is proving much more elusive. There have been
      over 1,000 significant variants found for many quantitative and binary traits yet
      they explain very little of the estimated genetic variance or heritability
      evident from family analysis. There are many hypotheses as to why this might be
      the case. This apparent lack of information is holding back the clinical
      application of genetics and shedding doubt on whether more of the same will
      reveal where the remainder of the variation lies. Here we explore the current
      state of play, the types of variants we can detect and how they are currently
      exploited. Finally we look at the future challenges we must face to persuade the
      human genome to yield its secrets.

PMID- 23115524
TI  - From genotype * environment interaction to gene * environment interaction.
AB  - Historically in plant breeding a large number of statistical models has been
      developed and used for studying genotype * environment interaction. These models
      have helped plant breeders to assess the stability of economically important
      traits and to predict the performance of newly developed genotypes evaluated
      under varying environmental conditions. In the last decade, the use of relatively
      low numbers of markers has facilitated the mapping of chromosome regions
      associated with phenotypic variability (e.g., QTL mapping) and, to a lesser
      extent, revealed the differetial response of these chromosome regions across
      environments (i.e., QTL * environment interaction). QTL technology has been
      useful for marker-assisted selection of simple traits; however, it has not been
      efficient for predicting complex traits affected by a large number of loci.
      Recently the appearance of cheap, abundant markers has made it possible to
      saturate the genome with high density markers and use marker information to
      predict genomic breeding values, thus increasing the precision of genetic value
      prediction over that achieved with the traditional use of pedigree information.
      Genomic data also allow assessing chromosome regions through marker effects and
      studying the pattern of covariablity of marker effects across differential
      environmental conditions. In this review, we outline the most important models
      for assessing genotype * environment interaction, QTL * environment interaction,
      and marker effect (gene) * environment interaction. Since analyzing genetic and
      genomic data is one of the most challenging statistical problems researchers
      currently face, different models from different areas of statistical research
      must be attempted in order to make significant progress in understanding genetic
      effects and their interaction with environment.

PMID- 23115525
TI  - Comparison of models for the collinearity of hox genes in the developmental axes
      of vertebrates.
AB  - Hox gene clusters are very frequent in many animal genomes and their role in
      development is pivotal. Particularly in vertebrates, intensive efforts have
      established several properties of Hox clusters. The collinearity of Hox gene
      expressions (spatial, temporal and quantitative) is a common feature of the
      vertebrates. During the last decade, genetic engineering experiments have
      revealed some important facets of collinearity during limb and trunk development
      in mice. Two models have been proposed to explain all these properties. On one
      hand the 'two-phases model' makes use of the molecular regulatory mechanisms
      acting on the Hox genes. On the other hand, the'biophysical model' is based on
      the signals transduced inside the cell nucleus and the generation of forces which
      apply on the cluster and lead to a coordinated activation of Hox genes. The two
      models differ fundamentally and a critical and detailed comparison is presented.
      Furthermore, experiments are proposed for which the two models provide divergent
      predictions. The outcome of these experiments will help to decide which of the
      two models is valid (if any).

PMID- 23115526
TI  - Do epigenetic marks govern bone mass and homeostasis?
AB  - Bone is a specialized connective tissue with a calcified extracellular matrix in
      which cells are embedded. Besides providing the internal support of the body and
      protection for vital organs, bone also has several important metabolic functions,
      especially in mineral homeostasis. Far from being a passive tissue, it is
      continuously being resorbed and formed again throughout life, by a process known
      as bone remodeling.Bone development and remodeling are influenced by many
      factors, some of which may be modifiable in the early steps of life. Several
      studies have shown that environmental factors in uterus and in infancy may modify
      the skeletal growth pattern, influencing the risk of bone disease in later life.
      On the other hand, bone remodeling is a highly orchestrated multicellular process
      that requires the sequential and balanced events of osteoclast-mediated bone
      resorption and osteoblast-mediated bone formation. These processes are
      accompanied by specific gene expression patterns which are responsible for the
      differentiation of the mesenchymal and hematopoietic precursors of osteoblasts
      and osteoclasts, respectively, and the activity of differentiated bone cells.
      This review summarizes the current understanding of how epigenetic mechanisms
      influence these processes and their possible role in common skeletal diseases.

PMID- 23115528
TI  - Azita madjidi, m.d., m.s.

PMID- 23115527
TI  - Targeting the Large Subunit of Human Ribonucleotide Reductase for Cancer
      Chemotherapy.
AB  - Ribonucleotide reductase (RR) is a crucial enzyme in de novo DNA synthesis, where
      it catalyses the rate determining step of dNTP synthesis. RRs consist of a large
      subunit called RR1 (alpha), that contains two allosteric sites and one catalytic
      site, and a small subunit called RR2 (beta), which houses a tyrosyl free radical
      essential for initiating catalysis. The active form of mammalian RR is an
      alpha(n)beta(m) hetero oligomer. RR inhibitors are cytotoxic to proliferating
      cancer cells. In this brief review we will discuss the three classes of RR, the
      catalytic mechanism of RR, the regulation of the dNTP pool, the substrate
      selection, the allosteric activation, inactivation by ATP and dATP, and the
      nucleoside drugs that target RR. We will also discuss possible strategies for
      developing a new class of drugs that disrupts the RR assembly.

PMID- 23115529
TI  - Historic aspects of ear reconstruction.

PMID- 23115530
TI  - Partial auricular reconstruction.
AB  - The authors summarize current methods for reconstructing partial auricular
      defects resulting from trauma, neoplasm, or congenital defects. They also review
      the anatomy and embryology of the ear as this is critical for proper
      reconstruction. Defects of the auricle are divided into upper-third, middle
      third, and lower-third defects. Methods of total auricular reconstruction are
      also briefly discussed as these methods can provide more superior reconstruction
      than partial techniques in select cases.

PMID- 23115531
TI  - A novel algorithm for autologous ear reconstruction.
AB  - Sculpting a tridimensional autologous rib cartilage framework is essential to
      restore a natural ear shape and becomes routine with preoperative training, but
      management of the skin is the key to minimizing complications. Here the authors
      provide a classification scheme to manage auricular skin: Type 1 is a Z-plasty
      with transposition of the lobule; type 2 is a transfixion incision of the
      microtic ear; type 3 exposes the cartilage remnants through a cutaneous incision.
      They also explain how to choose between the three types, depending upon the
      auricular skin potential. With training and method, results in ear reconstruction
      using autologous rib cartilage are excellent and reproducible.

PMID- 23115532
TI  - Prosthetic reconstruction of the auricle: indications, techniques, and results.
AB  - Extensive defects of the ear require satisfactory cosmetic reconstruction to
      enable the patient to achieve full social integration. Although surgical
      procedures are the gold standard for reconstruction of the ear, in some cases
      they cannot be performed because of extended scars, threatening tumor, or
      congenital tissue abnormalities. Prosthetic reconstruction of the auricle is an
      established and reliable alternative technique to autologous surgical
      reconstructions. Since studies performed by Branemark, osseointegrated implants
      have been widely used to provide a reliable and stable anchorage for a prosthesis
      (prosthesis anchored to bone). To allow good osseointegration of the titanium
      screw implants, two stages are necessary. After careful preparation for the
      surgical procedure (local and general examination, computed tomography scan, skin
      preparation), screws are implanted into bone, which are then covered by a skin
      flap. During the second stage, the skin is incised, and penetrating fixtures are
      attached to the screw implants, which allow fixation of the prosthesis. This
      procedure is reliable and reproducible, with good to excellent results and
      stability over time.

PMID- 23115533
TI  - Otologic and audiology aspects of microtia repair.
AB  - Congenital abnormalities of the outer ear pose a reconstructive challenge for
      plastic surgeons and otologists. Many patients with microtia of the auricle have
      concurrent atresia of the external auditory canal. The hearing loss associated
      with canal atresia can have long-lasting effects if not treated promptly and
      appropriately. The diagnosis and workup for canal atresia requires an otologic
      evaluation. Audiologic and radiologic evaluations direct treatment, which varies
      depending on unilateral or bilateral presence of atresia. Rehabilitation of
      hearing loss can be performed via hearing aids, bone-anchored conductive devices
      or canalplasty. Due to the complexity of treatments, communication between the
      reconstructive plastic surgeon and the otologist is necessary to detect hearing
      loss and determine the best method of restoring hearing in conjunction with
      microtia repair.

PMID- 23115534
TI  - Pathology of the ear.
AB  - The external ear is exposed to weathering and trauma; it also has sparse
      vascularity, making it prone to infection and disease. The external location of
      the cutaneous ear makes it easily visible for diagnosis and accessible for
      treatment. In this article, the authors focus on diseases of the ear that are
      most commonly encountered and may be subject to surgical and medical evaluation
      and/or treatment. Epidemiology, pathogenesis, clinical course, and treatment for
      each disease entity are discussed.

PMID- 23115535
TI  - Otoplasty for the protruded ear.
AB  - The prominent ear can produce significant social and psychological effects on an
      individual. Through the last century, many procedures have been described to
      correct this deformity. In this review, the authors navigate through the history
      of otoplasty for the protruded ear, and describe some of the breakthroughs in the
      procedure. Furthermore, they discuss key measurements that must be kept in mind
      in preoperative and intraoperative settings. They also describe in more detail
      some of the more common methods for correcting the protruded ear, as well as
      postoperative management and common complications faced after surgery.

PMID- 23115536
TI  - Nuclear medicine imaging in the pediatric patient.
AB  - Pediatric nuclear medicine provides a wealth of information on a variety of
      disease states; however, precautions on dosing have to be taken into
      consideration. Also, expertise in conducting procedures and interpreting the
      results in pediatric patients is necessary. Emphasis is placed on diagnostic
      studies involving the central nervous system, musculoskeletal system,
      genitourinary system, gastrointestinal system, endocrine system, pulmonary
      system, and cardiovascular system along with a brief explanation of the mechanism
      of localization of the radiopharmaceuticals involved. Radiation safety issues are
      addressed when the expectant mother or nursing mother is administered
      radiopharmaceuticals.

PMID- 23115537
TI  - Type 2 diabetes in children: a growing epidemic.
AB  - In the pediatric population, type 2 diabetes has become a growing concern. A
      correlation appears to exist among type 2 diabetes in children, obesity, and a
      sedentary lifestyle. If obesity and diabetes are left untreated, conditions such
      as cardiovascular disease, nephropathy, and retinopathy may result as well. These
      conditions indicate the incredible strain on the health care system caused by
      diabetes and obesity. This strain may be eased by logical treatments such as
      exercise and healthy eating habits for the child and family. However, these
      lifestyle changes are not always effective in controlling blood sugar. When
      lifestyle changes do not yield positive results, the clinician must decide which
      (if any) pharmacological treatments are safe to use in the pediatric population.
      Orlistat and sibutramine have been studied in children as treatments for obesity
      and appear to be safe and effective for this population. Metformin and insulin
      are among the medications approved to treat diabetes in children and adolescents.
      Healthcare practitioners must play a role in educating parents and their children
      about the effects of obesity on the development of diseases like diabetes, as
      well as various therapies used to manage diabetes. In addition, healthcare
      practitioners can assist patients and their parents in understanding the benefits
      and risks of medications used in the treatment of the disease, assistance that
      may result in them making informed decisions regarding their overall health.

PMID- 23115538
TI  - Assessing the guidelines for potassium replacement in pediatric oncology patients
      receiving amphotericin B.
AB  - OBJECTIVE: To examine the practice of potassium chloride (KCl) replacement in
      pediatric oncology patients receiving amphotericin B (amp-B). METHODS: A
      retrospective observational chart review was conducted of patients who received
      amp-B on the oncology unit between August 2000 and May 2001. A survey was
      distributed to pediatric oncology pharmacists at other pediatric institutions to
      assess KCl infusion guidelines across North America. RESULTS: Twenty hypokalemic
      episodes were identified within 22 patient admissions. Fifty-five percent used
      KCl replacement (by all combined routes) at rates exceeding the institution's
      guidelines. Other pediatric institutions varied with respect to the maximum rates
      and concentration of KCl permitted on non-intensive care units. CONCLUSIONS:
      Based on the data from this review, the KCl administration guidelines for our
      hospital were changed. We now allow a maximum peripheral line concentration of 60
      mEq/L, a maximum central line concentration of 120 mEq/L and a maximum KCl
      infusion rate of 0.4 mEq/kg/hr without the requirement of a heart monitor.
      Parenteral Nutrition is now restricted to maximum potassium concentration of 80
      mEq/L and fluid-restricted patients are restricted to a maximum concentration of
      150 mEq/L.

PMID- 23115539
TI  - Physical Compatibility of Alprostadil with Commonly Used IV Solutions and
      Medications in the Neonatal Intensive Care Unit.
AB  - OBJECTIVE: To determine the physical compatibility of alprostadil with
      intravenous (IV) solutions, a parenteral nutrition (PN) solution, and other
      intravenous medications commonly used in the neonatal intensive care unit (NICU).
      METHODS: To simulate y-site administration, each IV solution and the PN solution
      were slowly mixed 1:1 with alprostadil 15 MUg/mL at 25 degrees C. The mixtures
      were gently shaken and visually examined at 1, 15, 30, 45, and 60 minutes for
      physical incompatibility (gross precipitation, color change, haze, separation or
      gas production). In addition, each test tube was touched to assess for gross
      temperature change. The above mixtures were made a second time and each mixture
      was slowly mixed 1:1 with each of the test medications at 25 degrees C. The
      ampicillin-parenteral nutrition and the chlorothiazide-parenteral nutrition
      solution mixtures were not tested with alprostadil. The mixtures were examined
      for physical incompatibility as described above. RESULTS: Alprostadil was
      visually compatible with D5W 0.45% NaCl, D5W 0.45% NaCl with 20 mEq KCl/L, D10W
      0.45% NaCl, D10W 0.45% NaCl with 20mEq KCl/L, and a PN solution. Alprostadil was
      visually compatible with ampicillin, cefazolin, cefotaxime, chlorothiazide,
      dobutamine, dopamine, fentanyl, furosemide, gentamicin, methylprednisolone,
      tobramycin, vancomycin and vecuronium when mixed in D5W 0.45% NaCl, D5W 0.45%
      NaCl with 20mEq KCl/L, D10W 0.45% NaCl, and D10W 0.45% NaCl with 20mEq KCl/L.
      Alprostadil was visually compatible with cefazolin, cefotaxime, dobutamine,
      dopamine, fentanyl, furosemide, gentamicin, methylprednisolone, tobramycin,
      vancomycin and vecuronium when mixed in a PN solution. In addition, no gross
      temperature change was detected in any mixture. CONCLUSIONS: Based on the
      results, alprostadil is physically compatible with the tested IV solutions and a
      PN solution, as well as commonly prescribed IV medications used in the NICU when
      mixed with the tested IV solutions and a PN solution.

PMID- 23115540
TI  - Efficacy and economic evaluation of a volume-based cathflo activase protocol
      versus a fixed-dose alteplase protocol for catheter occlusions in pediatric
      patients.
AB  - OBJECTIVES: This prospective study evaluated the efficacy and economic benefit of
      Cathflo Activase and a volume-dependent protocol versus a previously utilized
      fixed-dose 2 mg/mL alteplase aliquot protocol for central venous catheter
      clearance in pediatric patients. METHODS: All pediatric patients with a medically
      diagnosed catheter occlusion were eligible for inclusion into this study.
      Retrospective data was analyzed from an approved data collection form, which had
      been implemented during the utilization of the alteplase protocol. Data
      collection indicators included catheter type, dose, dwell time, outcome of
      attempt (successful or unsuccessful), additional measures taken, and comments. A
      new protocol utilizing Cathflo Activase and manufacturer recommended volume-based
      dosing was prospectively implemented and data was collected and evaluated and
      compared to data from the alteplase protocol. RESULTS: Alteplase and Cathflo
      protocol data was evaluated for a total of 96 courses in 48 patients (0.09 - 22.8
      years, 2.15 - 105.2 kg). Complete resolution was achieved in 69.6% of patients
      with the alteplase protocol, partial resolution was attained in 8.7%, and
      treatment failure occurred in 21.7% of patients. For the Cathflo Activase group,
      complete resolution was observed in 82% of occlusions, with 8% partial resolution
      and treatment failure of 10%. The average cost per dose utilized by our patients
      during this study was $49.68 and $30.56 for the alteplase and Cathflo Activase
      groups, respectively. CONCLUSIONS: Our data indicate that the Cathflo Activase
      protocol may be as efficacious as the previous alteplase protocol. Furthermore,
      there are added time and cost benefits.

PMID- 23115541
TI  - Possible Ibuprofen-induced kernicterus in a near-term infant with moderate
      hyperbilirubinemia.
AB  - A 36-week gestation newborn was admitted to the neonatal intensive care unit for
      treatment of primary pulmonary hypertension and possible sepsis. The infant
      developed hyperbilirubinemia on day 4 of life and peaked on day 5 at a total
      serum bilirubin of 19 mg/dL. Phototherapy was started on day 4 and continued for
      5 days. On day 8 of life, ibuprofen was started for fever; a concurrent total
      serum bilirubin was 15.7 mg/dL. The subsequent hospital course was uneventful,
      and discharge occurred on day 22 of life. Because the patient failed a hearing
      screen at discharge, he was referred for a diagnostic audiology workup. He
      subsequently failed formal audiometric testing on two occasions one week apart,
      and was given a diagnosis of auditory dys-synchrony and/or auditory neuropathy,
      consistent with kernicterus. At 51/2 months of age, he was reported to be
      hypotonic and to have frequent arching movements. Since the total serum bilirubin
      did not exceed 19 mg/dL, concern was raised that ibuprofen may have caused
      displacement of bilirubin from its albumin binding site, resulting in kernicterus
      due to excessive unbound bilirubin concentrations. Ibuprofen should be
      administered with caution in preterm infants at risk for kernicterus.

PMID- 23115542
TI  - Gastric pH, GI Tract Bleeding, and Acid Suppression Therapy in Pediatric
      Patients.

PMID- 23115543
TI  - Pediatric news.

PMID- 23115545
TI  - Electroded avalanche amorphous selenium (a-Se) photosensor.
AB  - Although avalanche amorphous selenium (a-Se) is a very promising photoconductor
      for a variety of imaging applications, it is currently restricted to applications
      with electron beam readout in vacuum pick-up tube called a High-gain Avalanche
      Rushing Photoconductor (HARP). The electron beam readout is compatible with high
      definition television (HDTV) applications, but for use in solid-state medical
      imaging devices it should be replaced by an electronic readout with a two
      dimensional array of metal pixel electrodes. However, due to the high electric
      field required for avalanche multiplication, it is a technological challenge to
      avoid possible dielectric breakdown at the edges, where electric field
      experiences local enhancement. It has been shown recently that this problem can
      be overcome by the use of a Resistive Interface Layer (RIL) deposited between a
      Se and the metal electrode, however, at that time, at a sacrifice in transport
      properties.Here we show that optimization of RIL deposition technique allows for
      electroded avalanche a-Se with transport properties and time performance
      previously not achievable with any other a-Se structures. We have demonstrated
      this by detailed analysis of transport properties performed by Time-of-Flight
      (TOF) technique. Our results showed that a stable gain of 200 is reached at 104
      V/MUm for a 15-MUm thick a-Se layer, which is the maximum theoretical gain for
      this thickness. We conclude that RIL is an enabling technology for practical
      implementation of solid-state avalanche a-Se image sensors.

PMID- 23115546
TI  - Sterol composition of shellfish species commonly consumed in the United States.
AB  - BACKGROUND: Shellfish can be a component of a healthy diet due to a low fat and
      high protein content, but the cholesterol content of some species is often cited
      as a reason to limit their consumption. Data on levels of non-cholesterol sterols
      in commonly consumed species are lacking. OBJECTIVE: Shellfish were sampled and
      analyzed to update sterol data in the United States Department of Agriculture
      (USDA) National Nutrient Database for Standard Reference. DESIGN: Using a
      nationwide sampling plan, raw shrimp and sea scallops, canned clams, and steamed
      oysters, blue crab, and lobster were sampled from 12 statistically selected
      supermarkets across the United States in 2007-08. For each species, four
      composites were analyzed, each comprised of samples from three locations; shrimp
      and scallops from six single locations were also analyzed separately. Using
      validated analytical methodology, 14 sterols were determined in total lipid
      extracts after saponification and derivatization to trimethylsilyethers, using
      gas chromatography for quantitation and mass spectrometry for confirmation of
      components. RESULTS: Crab, lobster, and shrimp contained significant cholesterol
      (96.2-27 mg/100 g); scallops and clams had the lowest concentrations (23.4-30.1
      mg/100 g). Variability in cholesterol among single-location samples of shrimp was
      low. The major sterols in the mollusks were brassicasterol (12.6-45.6 mg/100 g)
      and 24-methylenecholesterol (16.7-41.9 mg/100 g), with the highest concentrations
      in oysters. Total non-cholesterol sterols were 46.5-75.6 mg/100 g in five single
      location scallops samples, but 107 mg/100 g in the sixth, with cholesterol also
      higher in that sample. Other prominent non-cholesterol sterols in mollusks were
      22-dehydrocholesterol, isofucosterol, clionasterol, campesterol, and 24
      norcholesta-5,22-diene-3beta-ol (4-21 mg/100 g). CONCLUSIONS: The presence of a
      wide range of sterols, including isomeric forms, in shellfish makes the analysis
      and quantitation of sterols in marine species more complex than in animal and
      plant tissues. The detailed sterol composition reported herein provides data that
      may be useful in research on the impact of shellfish consumption on dietary risk
      factors.

PMID- 23115547
TI  - A Neuronal Transcriptome Response Involving Stress Pathways is Buffered by
      Neuronal microRNAs.
AB  - A single microRNA (miRNA) can inhibit a large number of mRNA transcripts. This
      widespread regulatory function has been experimentally demonstrated for a number
      of miRNAs. However, even when a multitude of targets is confirmed, function of a
      miRNA is frequently interpreted through a prism of a handful arbitrarily selected
      "interesting" targets. In this work we first show that hundreds of transcripts
      with target sites for two miRNAs expressed endogenously in neurons, miR-124 and
      miR-434-3p, are coordinately upregulated in a variety of neuronal stresses. This
      creates a landscape where these two miRNAs can exert their widespread inhibitory
      potential on stress-induced transcripts. Next, we experimentally demonstrate that
      overexpression of these two miRNAs indeed significantly inhibits expression of
      hundreds of stress-induced transcripts, thus confirming that these transcripts
      are enriched in true targets of examined miRNAs. A number of miRNAs were
      previously shown to have important roles in the regulation of stress responses,
      and our results suggest that these roles should be understood in light of a wide
      spread activation of miRNA targets during stresses. Importantly, a popular
      cationic lipid transfection reagent triggers such induction of miRNA targets.
      Therefore, when a transfection paradigm is employed to study miRNA function, the
      results of such studies should be interpreted with consideration for the
      inadvertent induction of miRNA targets.

PMID- 23115548
TI  - Accurate reading with sequential presentation of single letters.
AB  - Rapid, accurate reading is possible when isolated, single words from a sentence
      are sequentially presented at a fixed spatial location. We investigated if
      reading of words and sentences is possible when single letters are rapidly
      presented at the fovea under user-controlled or automatically controlled rates.
      When tested with complete sentences, trained participants achieved reading rates
      of over 60 wpm and accuracies of over 90% with the single letter reading (SLR)
      method and naive participants achieved average reading rates over 30 wpm with
      greater than 90% accuracy. Accuracy declined as individual letters were presented
      for shorter periods of time, even when the overall reading rate was maintained by
      increasing the duration of spaces between words. Words in the lexicon that occur
      more frequently were identified with higher accuracy and more quickly,
      demonstrating that trained participants have lexical access. In combination, our
      data strongly suggest that comprehension is possible and that SLR is a
      practicable form of reading under conditions in which normal scanning of text is
      not possible, or for scenarios with limited spatial and temporal resolution such
      as patients with low vision or prostheses.

PMID- 23115549
TI  - The neural substrates of deliberative decision making: contrasting effects of
      hippocampus lesions on performance and vicarious trial-and-error behavior in a
      spatial memory task and a visual discrimination task.
AB  - Vicarious trial-and-errors (VTEs) are back-and-forth movements of the head
      exhibited by rodents and other animals when faced with a decision. These
      behaviors have recently been associated with prospective sweeps of hippocampal
      place cell firing, and thus may reflect a rodent model of deliberative decision
      making. The aim of the current study was to test whether the hippocampus is
      essential for VTEs in a spatial memory task and in a simple visual discrimination
      (VD) task. We found that lesions of the hippocampus with ibotenic acid produced a
      significant impairment in the accuracy of choices in a serial spatial reversal
      (SR) task. In terms of VTEs, whereas sham-lesioned animals engaged in more VTE
      behavior prior to identifying the location of the reward as opposed to repeated
      trials after it had been located, the lesioned animals failed to show this
      difference. In contrast, damage to the hippocampus had no effect on acquisition
      of a VD or on the VTEs seen in this task. For both lesion and sham-lesion
      animals, adding an additional choice to the VD increased the number of VTEs and
      decreased the accuracy of choices. Together, these results suggest that the
      hippocampus may be specifically involved in VTE behavior during spatial decision
      making.

PMID- 23115550
TI  - Male carriers of the FMR1 premutation show altered hippocampal-prefrontal
      function during memory encoding.
AB  - Previous functional MRI (fMRI) studies have shown that fragile X mental
      retardation 1 (FMR1) fragile X premutation allele carriers (FXPCs) exhibit
      decreased hippocampal activation during a recall task and lower inferior frontal
      activation during a working memory task compared to matched controls. The
      molecular characteristics of FXPCs includes 55-200 CGG trinucleotide expansions,
      increased FMR1 mRNA levels, and decreased FMRP levels especially at higher repeat
      sizes. In the current study, we utilized MRI to examine differences in
      hippocampal volume and function during an encoding task in young male FXPCs.
      While no decreases in either hippocampal volume or hippocampal activity were
      observed during the encoding task in FXPCs, FMRP level (measured in blood)
      correlated with decreases in parahippocampal activation. In addition, activity in
      the right dorsolateral prefrontal cortex during correctly encoded trials
      correlated negatively with mRNA levels. These results, as well as the established
      biological effects associated with elevated mRNA levels and decreased FMRP levels
      on dendritic maturation and axonal growth, prompted us to explore functional
      connectivity between the hippocampus, prefrontal cortex, and parahippocampal
      gyrus using a psychophysiological interaction analysis. In FXPCs, the right
      hippocampus evinced significantly lower connectivity with right ventrolateral
      prefrontal cortex (VLPFC) and right parahippocampal gyrus. Furthermore, the
      weaker connectivity between the right hippocampus and VLPFC was associated with
      reduced FMRP in the FXPC group. These results suggest that while FXPCs show
      relatively typical brain response during encoding, faulty connectivity between
      frontal and hippocampal regions may have subsequent effects on recall and working
      memory.

PMID- 23115551
TI  - Learning to use working memory: a reinforcement learning gating model of rule
      acquisition in rats.
AB  - Learning to form appropriate, task-relevant working memory representations is a
      complex process central to cognition. Gating models frame working memory as a
      collection of past observations and use reinforcement learning (RL) to solve the
      problem of when to update these observations. Investigation of how gating models
      relate to brain and behavior remains, however, at an early stage. The current
      study sought to explore the ability of simple RL gating models to replicate rule
      learning behavior in rats. Rats were trained in a maze-based spatial learning
      task that required animals to make trial-by-trial choices contingent upon their
      previous experience. Using an abstract version of this task, we tested the
      ability of two gating algorithms, one based on the Actor-Critic and the other on
      the State-Action-Reward-State-Action (SARSA) algorithm, to generate behavior
      consistent with the rats'. Both models produced rule-acquisition behavior
      consistent with the experimental data, though only the SARSA gating model
      mirrored faster learning following rule reversal. We also found that both gating
      models learned multiple strategies in solving the initial task, a property which
      highlights the multi-agent nature of such models and which is of importance in
      considering the neural basis of individual differences in behavior.

PMID- 23115552
TI  - Reduction of heart rate by omega-3 fatty acids and the potential underlying
      mechanisms.
AB  - An elevated resting heart rate is one of the strongest predictors of
      cardiovascular mortality and is independently associated with sudden cardiac
      death (SCD). Agents capable of reducing heart rate without significant side
      effects are therefore of particular interest for the prevention of SCD. Recent
      human and animal studies have shown that omega-3 fatty acids can reduce heart
      rate. Our work has shown that omega-3 fatty acids significantly reduce membrane
      electrical excitability of the cardiac myocyte by lowering its resting membrane
      potential and the duration of the refractory period through inhibition of ion
      channels. We propose that these actions may be the underlying mechanisms for the
      omega-3 fatty acid-induced reduction of heart rate observed in both humans and
      animals. The heart rate-lowering capability of omega-3 fatty acids may contribute
      to their preventive effect against SCD.

PMID- 23115553
TI  - The influence of baseline marijuana use on treatment of cocaine dependence:
      application of an informative-priors bayesian approach.
AB  - BACKGROUND: Marijuana use is prevalent among patients with cocaine dependence and
      often non-exclusionary in clinical trials of potential cocaine medications. The
      dual-focus of this study was to (1) examine the moderating effect of baseline
      marijuana use on response to treatment with levodopa/carbidopa for cocaine
      dependence; and (2) apply an informative-priors, Bayesian approach for estimating
      the probability of a subgroup-by-treatment interaction effect. METHOD: A
      secondary data analysis of two previously published, double-blind, randomized
      controlled trials provided complete data for the historical (Study 1: N = 64
      placebo), and current (Study 2: N = 113) data sets. Negative binomial regression
      evaluated Treatment Effectiveness Scores (TES) as a function of medication
      condition (levodopa/carbidopa, placebo), baseline marijuana use (days in past
      30), and their interaction. RESULTS: Bayesian analysis indicated that there was a
      96% chance that baseline marijuana use predicts differential response to
      treatment with levodopa/carbidopa. Simple effects indicated that among
      participants receiving levodopa/carbidopa the probability that baseline marijuana
      confers harm in terms of reducing TES was 0.981; whereas the probability that
      marijuana confers harm within the placebo condition was 0.163. For every
      additional day of marijuana use reported at baseline, participants in the
      levodopa/carbidopa condition demonstrated a 5.4% decrease in TES; while
      participants in the placebo condition demonstrated a 4.9% increase in TES.
      CONCLUSION: The potential moderating effect of marijuana on cocaine treatment
      response should be considered in future trial designs. Applying Bayesian subgroup
      analysis proved informative in characterizing this patient-treatment interaction
      effect.

PMID- 23115554
TI  - An fMRI Study of Neuronal Activation in Schizophrenia Patients with and without
      Previous Cannabis Use.
AB  - Previous studies have mostly shown positive effects of cannabis use on cognition
      in patients with schizophrenia, which could reflect lower neurocognitive
      vulnerability. There are however no studies comparing whether such cognitive
      differences have neuronal correlates. Thus, the aim of the present study was to
      compare whether patients with previous cannabis use differ in brain activation
      from patients who has never used cannabis. The patients groups were compared on
      the ability to up-regulate an effort mode network during a cognitive task and
      down-regulate activation in the same network during a task-absent condition. Task
      present and task-absent brain activation was measured by functional magnetic
      resonance neuroimaging (fMRI). Twenty-six patients with a DSM-IV and ICD-10
      diagnosis of schizophrenia were grouped into a previous cannabis user group and a
      no-cannabis group. An auditory dichotic listening task with instructions of
      attention focus on either the right or left ear stimulus was used to tap verbal
      processing, attention, and cognitive control, calculated as an aggregate score.
      When comparing the two groups, there were remaining activations in the task
      present condition for the cannabis group, not seen in the no-cannabis group,
      while there was remaining activation in the task-absent condition for the no
      cannabis group, not seen in the cannabis group. Thus, the patients with previous
      cannabis use showed increased activation in an effort mode network and decreased
      activation in the default mode network as compared to the no-cannabis group. It
      is concluded that the present study show some differences in brain activation to
      a cognitively challenging task between previous cannabis and no-cannabis
      schizophrenia patients.

PMID- 23115555
TI  - Augmentation of the sympathetic skin response after electrical train stimuli.
AB  - It is well known that the size of the sympathetic skin response (SSR) depends on
      the stimulus strength. In the present investigation train stimuli (TS) were
      employed to study the behavior of the SSR when recruited above the usual level.
      The SSR was obtained in healthy human subjects over the palm of the hand after
      supramaximal single stimuli (SS) and trains of three (TS; interstimulus interval
      3 ms) over the ipsilateral superficial radial nerve in 15 healthy volunteers.
      Ipsilateral to the stimulus site SSR amplitudes were 5.7 +/- 5.3 (SS) and 7.7 +/-
      5.9 mV (TS; p < 0.001), and contralateral 6.3 +/- 6.3 (SS) and 7.2 +/- 4.9 mV
      (TS; not significant). The relative gain in amplitude after TS vs. SS was
      negatively correlated with the SSR amplitude after SS ipsilateral (p < 0.0005)
      and contralateral to the stimulus site (p < 0.01). The increase in SSR amplitudes
      after TS compared with SS is in line with temporal summation of the excitatory
      synaptic input in neurons generating the SSR. Driving the SSR with TS is of
      possible relevance for the investigation of disorders of the peripheral or
      central autonomic nervous system.

PMID- 23115556
TI  - Brain neuropeptides in central ventilatory and cardiovascular regulation in
      trout.
AB  - Many neuropeptides and their G-protein coupled receptors (GPCRs) are present
      within the brain area involved in ventilatory and cardiovascular regulation but
      only a few mammalian studies have focused on the integrative physiological
      actions of neuropeptides on these vital cardio-respiratory regulations. Because
      both the central neuroanatomical substrates that govern motor ventilatory and
      cardiovascular output and the primary sequence of regulatory peptides and their
      receptors have been mostly conserved through evolution, we have developed a trout
      model to study the central action of native neuropeptides on cardio-ventilatory
      regulation. In the present review, we summarize the most recent results obtained
      using this non-mammalian model with a focus on PACAP, VIP, tachykinins, CRF,
      urotensin-1, CGRP, angiotensin-related peptides, urotensin-II, NPY, and PYY. We
      propose hypotheses regarding the physiological relevance of the results obtained.

PMID- 23115557
TI  - Mechanisms involved in VPAC receptors activation and regulation: lessons from
      pharmacological and mutagenesis studies.
AB  - Vasoactive intestinal peptide (VIP) plays diverse and important role in human
      physiology and physiopathology and their receptors constitute potential targets
      for the treatment of several diseases such as neurodegenerative disorder, asthma,
      diabetes, and inflammatory diseases. This article reviews the current knowledge
      regarding the two VIP receptors, VPAC(1) and VPAC(2), with respect to mechanisms
      involved in receptor activation, G protein coupling, signaling, regulation, and
      oligomerization.

PMID- 23115558
TI  - Current understanding of the Trypanosoma cruzi-cardiomyocyte interaction.
AB  - Trypanosoma cruzi, the etiological agent of Chagas disease, exhibits multiple
      strategies to ensure its establishment and persistence in the host. Although this
      parasite has the ability to infect different organs, heart impairment is the most
      frequent clinical manifestation of the disease. Advances in knowledge of T. cruzi
      cardiomyocyte interactions have contributed to a better understanding of the
      biological events involved in the pathogenesis of Chagas disease. This brief
      review focuses on the current understanding of molecules involved in T. cruzi
      cardiomyocyte recognition, the mechanism of invasion, and on the effect of
      intracellular development of T. cruzi on the structural organization and
      molecular response of the target cell.

PMID- 23115559
TI  - Glutamate receptor homologs in plants: functions and evolutionary origins.
AB  - The plant glutamate-like receptor homologs (GLRs) are homologs of mammalian
      ionotropic glutamate receptors (iGluRs) which were discovered more than 10 years
      ago, and are hypothesized to be potential amino acid sensors in plants. Although
      initial progress on this gene family has been hampered by gene redundancy and
      technical issues such as gene toxicity; genetic, pharmacological, and
      electrophysiological approaches are starting to uncover the functions of this
      protein family. In parallel, there has been tremendous progress in elucidating
      the structure of animal glutamate receptors (iGluRs), which in turn will help
      understanding of the molecular mechanisms of plant GLR functions. In this review,
      we will summarize recent progress on the plant GLRs. Emerging evidence implicates
      plant GLRs in various biological processes in and beyond N sensing, and implies
      that there is some overlap in the signaling mechanisms of amino acids between
      plants and animals. Phylogenetic analysis using iGluRs from metazoans, plants,
      and bacteria showed that the plant GLRs are no more closely related to metazoan
      iGluRs as they are to bacterial iGluRs, indicating the separation of plant, other
      eukaryotic, and bacterial GLRs might have happened as early on as the last
      universal common ancestor. Structural similarities and differences with animal
      iGluRs, and the implication thereof, are also discussed.

PMID- 23115560
TI  - Glucosinolates are produced in trichomes of Arabidopsis thaliana.
AB  - Glucosinolates (GS) are important plant secondary metabolites in plant resistance
      to herbivores, bacteria, and fungi, which have been shown to be accumulating in
      different organs and tissue types at varying concentrations. There are more than
      200 GS species found in order Brassicales and presence of these compounds is well
      documented on organ-specific but not on cell-specific level. We used UPLC/ESI
      QTOF-MS to measure the presence of GS and qRT-PCR to analyse the expression of GS
      biosynthetic and regulatory genes in isolated Arabidopsis thaliana trichomes.
      Trichomes of Arabidopsis are shown to synthesize chemoprotective aliphatic
      glucosinolates (AGS) and indolic glucosinolates (IGS), which are known for their
      biological activities against fungi, bacterial pathogens, or herbivores. UPLC/ESI
      QTOF-MS analysis of various IGS mutants reveal increased or decreased levels of
      IGS in trichomes of gain- and loss-of-function mutants correspondingly. Using
      pMYB51/HIG1-uidA and pMYB28/PMG1/HAG1-uidA reporter plants we demonstrate that
      production of these important compounds is activated in trichomes of leaves or
      inflorescences in response to wounding. Since trichomes represent the first
      interface in plant-environment interactions, the possible role of GS containing
      trichomes in plant defense or signaling is discussed.

PMID- 23115561
TI  - Resource limitation, tolerance, and the future of ecological plant
      classification.
AB  - Throughout the evolutionary history of plants, drought, shade, and scarcity of
      nutrients have structured ecosystems and communities globally. Humans have begun
      to drastically alter the prevalence of these environmental factors with untold
      consequences for plant communities and ecosystems worldwide. Given limitations in
      using organ-level traits to predict ecological performance of species, recent
      advances using tolerances of low resource availability as plant functional traits
      are revealing the often hidden roles these factors have in structuring
      communities and are becoming central to classifying plants ecologically. For
      example, measuring the physiological drought tolerance of plants has increased
      the predictability of differences among species in their ability to survive
      drought as well as the distribution of species within and among ecosystems.
      Quantifying the shade tolerance of species has improved our understanding of
      local and regional species diversity and how species have sorted within and among
      regions. As the stresses on ecosystems continue to shift, coordinated studies of
      whole-plant growth centered on tolerance of low resource availability will be
      central in predicting future ecosystem functioning and biodiversity. This will
      require efforts that quantify tolerances for large numbers of species and develop
      bioinformatic and other techniques for comparing large number of species.

PMID- 23115562
TI  - Lack of miRNA Misregulation at Early Pathological Stages in Drosophila
      Neurodegenerative Disease Models.
AB  - Late onset neurodegenerative diseases represent a major public health concern as
      the population in many countries ages. Both frequent diseases such as Alzheimer
      disease (AD, 14% incidence for 80-84 year-old Europeans) or Parkinson disease
      (PD, 1.4% prevalence for >55 years old) share, with other low-incidence
      neurodegenerative pathologies such as spinocerebellar ataxias (SCAs, 0.01%
      prevalence) and frontotemporal lobar degeneration (FTLD, 0.02% prevalence), a
      lack of efficient treatment in spite of important research efforts. Besides
      significant progress, studies with animal models have revealed unexpected
      complexities in the degenerative process, emphasizing a need to better understand
      the underlying pathological mechanisms. Recently, microRNAs (miRNAs), a class of
      small regulatory non-coding RNAs, have been implicated in some neurodegenerative
      diseases. The current data supporting a role of miRNAs in PD, tauopathies,
      dominant ataxias, and FTLD will first be discussed to emphasize the different
      levels of the pathological processes which may be affected by miRNAs. To
      investigate a potential involvement of miRNA dysregulation in the early stages of
      these neurodegenerative diseases we have used Drosophila models for seven
      diseases (PD, 3 FTLD, 3 dominant ataxias) that recapitulate many features of the
      human diseases. We performed deep sequencing of head small RNAs after 3 days of
      pathological protein expression in the fly head neurons. We found no evidence for
      a statistically significant difference in miRNA expression in this early stage of
      the pathological process. In addition, we could not identify small non-coding CAG
      repeat RNAs (sCAG) in polyQ disease models. Thus our data suggest that
      transcriptional deregulation of miRNAs or sCAG is unlikely to play a significant
      role in the initial stages of neurodegenerative diseases.

PMID- 23115563
TI  - Understanding the people who provide care.

PMID- 23115564
TI  - Comprendre les personnes qui fournissent des soins.

PMID- 23115565
TI  - The Sorcerer's Apprentices.
AB  - Riding concerns about physician shortages, Canadian medical schools have expanded
      their annual enrolment by 80% over the last 13 years. Including rapid growth in
      net immigration, the annual "crop" has nearly doubled. (Population has grown by
      about 14%.) The physician workforce is just now showing the impact - a 6%
      increase in physicians per capita in the last three years. In the last decade,
      medical expenditure per physician has also risen, by nearly 35% above general
      inflation. The drivers are rapidly increasing diagnostic testing and imaging, and
      the growth of alternative payment programs. More doctors, combined with growing
      expenditure per doctor, will have serious cost implications. What benefits are we
      buying?

PMID- 23115566
TI  - The hard work of balancing employment and caregiving: what can canadian employers
      do to help?
AB  - As a result of population aging and changing family structures, more Canadians
      than ever are balancing careers with family caregiving responsibilities. Previous
      research has suggested that different policy responses are required to support
      caregivers, depending on the intensity of their caregiving contributions. This
      discussion paper focuses on needed workplace supports for family caregivers in
      Canada, with a specific emphasis on the role for employers. Outlined are
      challenges faced by caregiving employees, the ways in which employers and
      governments are already supporting caregivers internationally, and options for
      how Canadian employers might participate in creating caregiver-friendly
      workplaces.

PMID- 23115567
TI  - Policy to practice: collaboration in the evolution of a nursing health human
      resources policy.
AB  - In 2007, the Ontario Ministry of Health and Long-Term Care made an investment to
      support full-time employment for new graduate nurses. This paper describes the
      collaboration of policy makers and researchers in the creation and implementation
      of the Nursing Graduate Guarantee (NGG). We provide historical context for the
      development of the initiative and discuss some of the issues related to its
      implementation. Relevant stakeholders assisted researchers and policy makers in
      the creation, implementation and evaluation of the NGG. Researchers continue to
      work with policy makers in ongoing evaluations of the multi-year strategy, which
      are informed by stakeholder input.

PMID- 23115568
TI  - Where Are Ontario's Respiratory Therapists Working?
AB  - Registered respiratory therapists (RRTs) aid in the diagnosis and treatment of
      respiratory illness and cardiopulmonary disorders, conditions that are
      increasingly being managed in settings other than the hospital sector. However,
      analysis of a longitudinal data set of Ontario's RRTs (2,903) from 1996 to 2007
      demonstrates that the majority of RRTs work full-time in the hospital sector,
      where retention is high. Despite a policy direction encouraging the shift of the
      site of care from the hospital sector to the community/home, this has had little
      impact on where RRTs work, raising the question of who is providing respiratory
      services in the community.

PMID- 23115569
TI  - Workforce integration of new graduate nurses: evaluation of a health human
      resources employment policy.
AB  - Historically, economic changes have negatively affected the nursing workforce in
      Ontario. The trend towards part-time and casual employment emerged from
      healthcare restructuring in the 1990s. The severe acute respiratory syndrome
      (SARS) outbreak in 2003 alerted the Ontario government to the issue of part-time
      and casual nursing. In 2007, the Nursing Graduate Guarantee (NGG), a health human
      resources employment policy, was developed as a financial incentive for employers
      to hire and mentor new graduate nurses for a six-month period. The purpose of
      this study was to examine facilitators and barriers to policy implementation and
      assess the impact of the NGG on full-time employment and workforce integration of
      new graduate nurses in Ontario. A mixed-methods approach was used and included
      surveys, interviews and focus groups. Results indicated that full-time employment
      of new graduate nurses increased during the study period and that mentorship
      facilitated workforce integration of new graduate nurses.

PMID- 23115570
TI  - The shifting landscape of immigration policy in Canada: implications for health
      human resources.
AB  - For many years, Canada has relied on international migration to compensate for
      cyclical shortages in its skilled labour force. This paper reports on recent
      changes in Canadian immigration policy, namely, the introduction of new
      immigration programs focused on skilled workers, along with the implementation of
      domestic mobility agreements. With specific reference to the case of nursing, the
      paper highlights the necessity for integrated policy across multiple government
      levels and stakeholder groups, as well as the need to promote the development of
      evidence-based policy in the fields of immigration and health human resources.

PMID- 23115571
TI  - Understanding how context shapes citizen-user involvement in policy making.
AB  - As governments grapple with meeting expectations of citizens and including their
      voices in policy making, greater understanding of how context influences
      involvement can help identify ways to involve those citizens who face substantial
      barriers to inclusion in policy development. This qualitative, instrumental case
      study focused on the involvement of people who use and need mental health and
      housing services in policy development in Manitoba. Data were collected from 21
      key informants purposively selected from four policy actor groups as well as from
      relevant documents. Data were analyzed using inductive qualitative methods.
      Results identified five themes related to contextual influences on involvement:
      (a) the social environment, (b) institutional characteristics, (c) participant
      characteristics, (d) opportunities for involvement and (e) ideas and formal
      policy structures. The findings suggest that policy makers should look to
      contextual factors to identify ways to reduce the barriers to the inclusion of
      people with mental health and housing needs in health policy making.

PMID- 23115572
TI  - Knowledge translation in mental health: a scoping review.
AB  - Intensified knowledge translation (KT) efforts are considered important in the
      field of mental health in order to accelerate the implementation of various
      developments in research, policy and practice. A scoping review of KT focused on
      the field of mental health was undertaken to help inform development of a
      Knowledge Exchange Centre being initiated by the Mental Health Commission of
      Canada. A systematic search of publications in English and French identified 187
      publications that met inclusion criteria. Relevant literature was found across a
      number of disparate thematic research areas: implementation science, community
      based and participatory action research, shared decision-making studies, mental
      health literacy research, network analysis and studies directly addressing KT.
      The available literature is concerned predominantly with KT efforts between a few
      specific stakeholder dyads. A paradigm shift has been emerging and has resulted
      in a progressively broader perspective, incorporating a wider range of
      participants and increased valuing of experiential knowledge.

PMID- 23115574
TI  - Cost-effectiveness analysis of a reduction in diagnostic imaging in degenerative
      spinal disorders.
AB  - BACKGROUND: Advanced imaging technologies such as computed tomography (CT) and
      magnetic resonance imaging (MRI) are highly sensitive, but often non-specific,
      diagnostic tools. Despite this, CT and MRI are overutilized in degenerative
      spinal disorder diagnosis. From the perspective of the Ministry of Health, we
      evaluated against usual care the cost-effectiveness of a hypothetical triage
      program for non-emergent spinal disorders that reduces unnecessary imaging uses.
      METHODS: Diagnostic and surgical data were prospectively collected on 2,046
      outpatients who received consultation with the senior surgical author at Toronto
      Western Hospital, University Health Network, between September 2005 and April
      2008. Using these data, we modelled an evidence-based diagnostic triage program
      wherein spine-focused clinical assessments and plain X-ray imaging would be
      applied prior to CT and MRI. Incremental costs were the incurred expenses from
      additional consultations and plain X-rays less the cost savings from the
      eliminated CT and MRI scans, expressed in 2009 Canadian dollars. Outcomes were
      expressed as the number of surgical candidates identified per MRI used in
      diagnosis, reflecting the efficiency of diagnostic imaging. RESULTS: The triage
      program incurred $109,720 from additional consultations and plain X-rays and
      saved $2,117,697 from eliminated CT and MRI scans, resulting in net cost savings
      of $2,007,977 for the 31 months of the study period, or $777,282 per year. In
      usual care, 0.328~0.418 surgical candidates were identified per MRI whereas in
      the triage program, 0.736~0.885 surgical candidates were identified per MRI,
      resulting in over a twofold improvement in MRI efficiency. The triage program was
      therefore dominating. Applying to high-volume spine surgeons in Ontario, we
      estimated that the implementation of the triage program would save the province
      $24,234,929 per year. INTERPRETATION: Based on the assumptions made in our
      modelling, eliminating unnecessary imaging in spinal disorder diagnosis can save
      healthcare significant resources.

PMID- 23115575
TI  - Primary Care Reform: Can Quebec's Family Medicine Group Model Benefit from the
      Experience of Ontario's Family Health Teams?
AB  - Canadian politicians, decision-makers, clinicians and researchers have come to
      agree that reforming primary care services is a key strategy for improving
      healthcare system performance. However, it is only more recently that real
      transformative initiatives have been undertaken in different Canadian provinces.
      One model that offers promise for improving primary care service delivery is the
      family medicine group (FMG) model developed in Quebec. A FMG is a group of
      physicians working closely with nurses in the provision of services to enrolled
      patients on a non-geographic basis. The objectives of this paper are to analyze
      the FMG's potential as a lever for improving healthcare system performance and to
      discuss how it could be improved. First, we briefly review the history of primary
      care in Quebec. Then we present the FMG model in relation to the four key
      healthcare system functions identified by the World Health Organization: (a)
      funding, (b) generating human and technological resources, (c) providing services
      to individuals and communities and (d) governance. Next, we discuss possible ways
      of advancing primary care reform, looking particularly at the family health team
      (FHT) model implemented in the province of Ontario. We conclude with
      recommendations to inspire other initiatives aimed at transforming primary care.

PMID- 23115576
TI  - Women and hysteria in the history of mental health.
AB  - Hysteria is undoubtedly the first mental disorder attributable to women,
      accurately described in the second millennium BC, and until Freud considered an
      exclusively female disease. Over 4000 years of history, this disease was
      considered from two perspectives: scientific and demonological. It was cured with
      herbs, sex or sexual abstinence, punished and purified with fire for its
      association with sorcery and finally, clinically studied as a disease and treated
      with innovative therapies. However, even at the end of 19(th) century, scientific
      innovation had still not reached some places, where the only known therapies were
      those proposed by Galen. During the 20(th) century several studies postulated the
      decline of hysteria amongst occidental patients (both women and men) and the
      escalating of this disorder in non-Western countries. The concept of hysterical
      neurosis is deleted with the 1980 DSM-III. The evolution of these diseases seems
      to be a factor linked with social "westernization", and examining under what
      conditions the symptoms first became common in different societies became a
      priority for recent studies over risk factor.

PMID- 23115577
TI  - Linking Students' Emotions and Academic Achievement: When and Why Emotions
      Matter.
AB  - Few studies include associations of emotions, or of individual differences in
      emotionality, to academic competence, and there are virtually no empirical data
      on when or why relations exist (or do not exist). The few studies of emotion and
      achievement have largely focused on anxiety, but there has been scant theoretical
      and empirical attention devoted to the treatment of other emotions. It is
      suggested that considering the moderated and indirect effects of students'
      emotions on their academic functioning may provide an understanding of whether
      and under what circumstances emotions are related to achievement. This article
      briefly reviews findings linking situational and dispositional negative or
      positive emotions to academic achievement and suggests that researchers can learn
      much about relations between emotions and achievement by considering the
      potential moderating role of effortful control, as well as considering the
      mediating roles that cognitive processes, motivational mechanisms, and classroom
      relationships play in linking emotions and achievement.

PMID- 23115578
TI  - Effect of play between bracket and archwire on anterior tooth movement in sliding
      mechanics: A three-dimensional finite element study.
AB  - OBJECTIVES: The aim of this study was to clarify the effect of the play between
      the bracket and the archwire on anterior tooth movement subjected to the
      retraction force from various lengths of power arms in sliding mechanics.
      MATERIALS AND METHODS: A three-dimensional finite element method was used to
      simulate en masse anterior tooth retraction in sliding mechanics. The
      displacements of the maxillary incisor and the archwire deformation were
      calculated when the retraction force was applied. RESULTS: When a play did not
      exist, bodily movement was obtained at 5.0 mm length of power arm. In case a play
      existed, bodily movement was observed at the power arm length of 11.0 mm.
      CONCLUSIONS: In the actual clinical situation, a bracket/archwire play and the
      torsion of the archwire within the bracket slot should be taken into
      consideration to prescribe an optimal power arm length and to achieve effective
      anterior tooth movement.

PMID- 23115579
TI  - Musculoskeletal manifestations in diabetic patients at a tertiary center.
AB  - OBJECTIVES: Diabetes mellitus is a major public health problem worldwide. Most
      diabetic patients will develop functional disabilities due to multiple factors,
      including musculoskeletal (MSK) manifestations. The purpose of this study was to
      determine the frequency of MSK in diabetic patients and to examine the possible
      predictors for its development. METHODS: We performed a cross-sectional study
      from June 1, 2010, to June 30, 2011, to evaluate MSK manifestations in adult
      diabetic patients at an outpatient clinic of King Abdulaziz University Hospital,
      Jeddah, Saudi Arabia. Baseline variables were examined to determine predictors
      for the development of MSK complications. Analyses were carried out using the
      Statistical Package for Social sciences. RESULTS: We included 252 diabetic
      patients; 45 (17.9%) had MSK manifestations. Of these 45 patients, 41 (91.1%) had
      type 2 diabetes. The most common manifestations were carpal tunnel syndrome
      (n=17, 6.7%), shoulder adhesive capsulitis (n=17, 6.7%), and diabetic amyotrophy
      (n=12, 4.8%). A significant association was found between the development of MSK
      manifestations and manual labor, overweight, and vascular complications. On
      logistic regression analysis, the presence of vascular complications in general
      (B-coefficient=1.27, odds ratio=3.57, P<0.05, 95% confidence interval=1.31-9.78),
      and retinopathy in particular (B-coefficient=1.17, odds ratio=3.21, P<0.05, 95%
      confidence interval=1.47-7.02) can predict the development of MSK manifestations
      in about 82% of the cases. CONCLUSION: Musculoskeletal manifestations are under
      recognized in adult diabetic patients, occurring in 18% of the cases. Physicians
      should consider examining the periarticular region of the joints in the hands and
      shoulders whenever a diabetic patient presents with MSK symptoms.

PMID- 23115580
TI  - Advances in artificial intelligence research in health.

PMID- 23115581
TI  - Extractive summarisation of medical documents using domain knowledge and corpus
      statistics.
AB  - BACKGROUND: Evidence Based Medicine (EBM) practice requires practitioners to
      extract evidence from published medical research when answering clinical queries.
      Due to the time- consuming nature of this practice, there is a strong motivation
      for systems that can automatically summarise medical documents and help
      practitioners find relevant information. AIM: The aim of this work is to propose
      an automatic query- focused, extractive summarisation approach that selects
      informative sentences from medical documents. METHOD: We use a corpus that is
      specifically designed for summarisation in the EBM domain. We use approximately
      half the corpus for deriving important statistics associated with the best
      possible extractive summaries. We take into account factors such as sentence
      position, length, sentence content, and the type of the query posed. Using the
      statistics from the first set, we evaluate our approach on a separate set.
      Evaluation of the qualities of the generated summaries is performed automatically
      using ROUGE, which is a popular tool for evaluating automatic summaries. RESULTS:
      Our summarisation approach outperforms all baselines (best baseline score:
      0.1594; our score 0.1653). Further improvements are achieved when query types are
      taken into account. CONCLUSION: The quality of extractive summarisation in the
      medical domain can be significantly improved by incorporating domain knowledge
      and statistics derived from a specialised corpus. Such techniques can therefore
      be applied for content selection in end-to-end summarisation systems.

PMID- 23115582
TI  - Towards semantic search and inference in electronic medical records: An approach
      using concept--based information retrieval.
AB  - BACKGROUND: This paper presents a novel approach to searching electronic medical
      records that is based on concept matching rather than keyword matching. AIM: The
      concept-based approach is intended to overcome specific challenges we identified
      in searching medical records. METHOD: Queries and documents were transformed from
      their term-based originals into medical concepts as defined by the SNOMED-CT
      ontology. RESULTS: Evaluation on a real-world collection of medical records
      showed our concept-based approach outperformed a keyword baseline by 25% in Mean
      Average Precision. CONCLUSION: The concept-based approach provides a framework
      for further development of inference based search systems for dealing with
      medical data.

PMID- 23115583
TI  - Automated medical literature retrieval.
AB  - BACKGROUND: The constantly growing publication rate of medical research articles
      puts increasing pressure on medical specialists who need to be aware of the
      recent developments in their field. The currently used literature retrieval
      systems allow researchers to find specific papers; however the search task is
      still repetitive and time-consuming. AIM: In this paper we describe a system that
      retrieves medical publications by automatically generating queries based on data
      from an electronic patient record. This allows the doctor to focus on medical
      issues and provide an improved service to the patient, with higher confidence
      that it is underpinned by current research. METHOD: Our research prototype
      automatically generates query terms based on the patient record and adds weight
      factors for each term. Currently the patient's age is taken into account with a
      fuzzy logic derived weight, and terms describing blood-related anomalies are
      derived from recent blood test results. Conditionally selected homonyms are used
      for query expansion. The query retrieves matching records from a local index of
      PubMed publications and displays results in descending relevance for the given
      patient. Recent publications are clearly highlighted for instant recognition by
      the researcher. RESULTS: Nine medical specialists from the Royal Adelaide
      Hospital evaluated the system and submitted pre-trial and post-trial
      questionnaires. Throughout the study we received positive feedback as doctors
      felt the support provided by the prototype was useful, and which they would like
      to use in their daily routine. CONCLUSION: By supporting the time-consuming task
      of query formulation and iterative modification as well as by presenting the
      search results in order of relevance for the specific patient, literature
      retrieval becomes part of the daily workflow of busy professionals.

PMID- 23115584
TI  - A causal model for fluctuating sugar levels in diabetes patients.
AB  - BACKGROUND: Causal models of physiological systems can be immensely useful in
      medicine as they may be used for both diagnostic and therapeutic reasoning. AIM:
      In this paper we investigate how an agent may use the theory of belief change to
      rectify simple causal models of changing blood sugar levels in diabetes patients.
      METHOD: We employ the semantic approach to belief change together with a popular
      measure of distance called Dalal distance between different state descriptions in
      order to implement a simple application that simulates the effectiveness of the
      proposed method in helping an agent rectify a simple causal model. RESULTS: Our
      simulation results show that distance-based belief change can help in improving
      the agent's causal knowledge. However, under the current implementation there is
      no guarantee that the agent will learn the complete model and the agent may at
      times get stuck in local optima. CONCLUSION: Distance-based belief change can
      help in refining simple causal models such as the example in this paper. Future
      work will include larger state-action spaces, better distance measures and
      strategies for choosing actions.

PMID- 23115585
TI  - Creation of a corpus for evidence based medicine summarisation.
AB  - BACKGROUND: Automated text summarisers that find the best clinical evidence
      reported in collections of medical literature are of potential benefit for the
      practice of Evidence Based Medicine (EBM). Research and development of text
      summarisers for EBM, however, is impeded by the lack of corpora to train and test
      such systems. AIMS: To produce a corpus for research in EBM summarisation.
      METHOD: We sourced the "Clinical Inquiries" section of the Journal of Family
      Practice (JFP) and obtained a sizeable sample of questions and evidence based
      summaries. We further processed the summaries by combining automated techniques,
      human annotations, and crowdsourcing techniques to identify the PubMed IDs of the
      references. RESULTS: The corpus has 456 questions, 1,396 answer components, 3,036
      answer justifications, and 2,908 references. CONCLUSION: The corpus is now
      available for the research community at
      http://sourceforge.net/projects/ebmsumcorpus.

PMID- 23115586
TI  - Retinal image registration and comparison for clinical decision support.
AB  - BACKGROUND: For eye diseases, such as glaucoma and age-related macular
      degeneration (ARMD), involved in long-term degeneration procedure, longitudinal
      comparison of retinal images is a common step for reliable diagnosis of these
      kinds of diseases. AIMS: To provide a retinal image registration approach for
      longitudinal retinal image alignment and comparison. METHOD: Two image
      registration solutions were proposed for facing different image qualities of
      retinal images to make the registration methods more robust and feasible in a
      clinical application system. RESULTS: Thirty pairs of longitudinal retinal images
      were used for the registration test. The experiments showed both solutions
      provided good performance for the accurate image registrations with efficiency.
      CONCLUSION: We proposed a set of retinal image registration solutions for
      longitudinal retinal image observation and comparison targeting a clinical
      application environment.

PMID- 23115587
TI  - Doctors and medical training.

PMID- 23115588
TI  - Improving self-care of patients with chronic disease using online personal health
      record.
AB  - BACKGROUND: Effective management of chronic diseases such as prostate cancer is
      important. Research suggests a tendency to use self-care treatment options such
      as over-the-counter (OTC) complementary medications among prostate cancer
      patients. The current trend in patient-driven recording of health data in an
      online Personal Health Record (PHR) presents an opportunity to develop new data
      driven approaches for improving prostate cancer patient care. However, the
      ability of current online solutions to share patients' data for better decision
      support is limited. An informatics approach may improve online sharing of self
      care interventions among these patients. It can also provide better evidence to
      support decisions made during their self-managed care. AIMS: To identify
      requirements for an online system and describe a new case-based reasoning (CBR)
      method for improving self-care of advanced prostate cancer patients in an online
      PHR environment. METHOD: A non-identifying online survey was conducted to
      understand self-care patterns among prostate cancer patients and to identify
      requirements for an online information system. The pilot study was carried out
      between August 2010 and December 2010. A case-base of 52 patients was developed.
      RESULTS: The data analysis showed self-care patterns among the prostate cancer
      patients. Selenium (55%) was the common complementary supplement used by the
      patients. Paracetamol (about 45%) was the commonly used OTC by the patients.
      CONCLUSION: The results of this study specified requirements for an online case
      based reasoning information system. The outcomes of this study are being
      incorporated in design of the proposed Artificial Intelligence (Al) driven
      patient journey browser system. A basic version of the proposed system is
      currently being considered for implementation.

PMID- 23115589
TI  - Selecting EEG components using time series analysis in brain death diagnosis.
AB  - In diagnosis of brain death for human organ transplant, EEG
      (electroencephalogram) must be flat to conclude the patient's brain death but it
      has been reported that the flat EEG test is sometimes difficult due to artifacts
      such as the contamination from the power supply and ECG (electrocardiogram, the
      signal from the heartbeat). ICA (independent component analysis) is an effective
      signal processing method that can separate such artifacts from the EEG signals.
      Applying ICA to EEG channels, we obtain several separated components among which
      some correspond to the brain activities while others contain artifacts. This
      paper aims at automatic selection of the separated components based on time
      series analysis. In the flat EEG test in brain death diagnosis, such automatic
      component selection is helpful.

PMID- 23115590
TI  - Bottom-up attention: pulsed PCA transform and pulsed cosine transform.
AB  - In this paper we propose a computational model of bottom-up visual attention
      based on a pulsed principal component analysis (PCA) transform, which simply
      exploits the signs of the PCA coefficients to generate spatial and motional
      saliency. We further extend the pulsed PCA transform to a pulsed cosine transform
      that is not only data-independent but also very fast in computation. The proposed
      model has the following biological plausibilities. First, the PCA projection
      vectors in the model can be obtained by using the Hebbian rule in neural
      networks. Second, the outputs of the pulsed PCA transform, which are inherently
      binary, simulate the neuronal pulses in the human brain. Third, like many Fourier
      transform-based approaches, our model also accomplishes the cortical center
      surround suppression in frequency domain. Experimental results on psychophysical
      patterns and natural images show that the proposed model is more effective in
      saliency detection and predict human eye fixations better than the state-of-the
      art attention models.

PMID- 23115591
TI  - Spatiotemporal characteristics of synaptic EPSP summation on the dendritic trees
      of hippocampal CA1 pyramidal neurons as revealed by laser uncaging stimulation.
AB  - Synaptic strength is modified by the temporal coincidence of synaptic inputs
      without back-propagating action potentials (BPAPs) in CA1 pyramidal neurons. In
      order to clarify the interactive mechanisms of associative long-term potentiation
      (LTP) without BPAPs, local paired stimuli were applied to the dendrites using
      high-speed laser uncaging stimulation equipment. When the spatial distance
      between the paired stimuli was <10 micrometer, nonlinear amplification in
      excitatory postsynaptic potential summation was observed. In the time window from
      -20 to 20 ms, supralinear amplification was observed. Supralinear amplification
      was modulated by antagonist of voltage-gated Na(+)/Ca(2+) channels and NMDA-type
      glutamate receptors. These results are closely related to the spatiotemporal
      characteristics of associative LTP without BPAPs. This study proposes an
      essential aspect of dendritic information processing.

PMID- 23115592
TI  - Answering six questions in extracting children's mismatch negativity through
      combining wavelet decomposition and independent component analysis.
AB  - This study combines wavelet decomposition and independent component analysis
      (ICA) to extract mismatch negativity (MMN) from electroencephalography (EEG)
      recordings. As MMN is a small event-related potential (ERP), a systematic ICA
      based approach is designed, exploiting MMN's temporal, frequency and spatial
      information. Moreover, this study answers which type of EEG recordings is more
      appropriate for ICA to extract MMN, what kind of the preprocessing is beneficial
      for ICA decomposition, which algorithm of ICA can be chosen to decompose EEG
      recordings under the selected type, how to determine the desired independent
      component extracted by ICA, how to improve the accuracy of the back projection of
      the selected independent component in the electrode field, and what can be
      finally obtained with the application of ICA. Results showed that the proposed
      method extracted MMN with better properties than those estimated by difference
      wave only using temporal information or ICA only using spatial information. The
      better properties mean that the deviant with larger magnitude of deviance to
      repeated stimuli in the oddball paradigm can elicit MMN with larger peak
      amplitude and shorter latency. As other ERPs also have the similar information
      exploited here, the proposed method can be used to study other ERPs.

PMID- 23115593
TI  - Synchronization of chaotic nonlinear continuous neural networks with time-varying
      delay.
AB  - In this paper, the synchronization problem for delayed continuous time nonlinear
      complex neural networks is considered. The delay dependent state feed back
      synchronization gain matrix is obtained by considering more general case of time
      varying delay. Using Lyapunov stability theory, the sufficient synchronization
      criteria are derived in terms of Linear Matrix Inequalities (LMIs). By
      decomposing the delay interval into multiple equidistant subintervals, Lyapunov
      Krasovskii functionals (LKFs) are constructed on these intervals. Employing these
      LKFs, new delay dependent synchronization criteria are proposed in terms of LMIs
      for two cases with and without derivative of time-varying delay. Numerical
      examples are illustrated to show the effectiveness of the proposed method.

PMID- 23115594
TI  - Finite-time synchronization of coupled neural networks via discontinuous
      controllers.
AB  - This paper investigates finite-time synchronization of an array of coupled neural
      networks via discontinuous controllers. Based on Lyapunov function method and the
      discontinuous version of finite-time stability theory, some sufficient criteria
      for finite-time synchronization are obtained. Furthermore, we propose switched
      control and adaptive tuning parameter strategies in order to reduce the settling
      time. In addition, pinning control scheme via a single controller is also studied
      in this paper. With the hypothesis that the coupling network topology contains a
      directed spanning tree and each of the strongly connected components is detail
      balanced, we prove that finite-time synchronization can be achieved via pinning
      control. Finally, some illustrative examples are given to show the validity of
      the theoretical results.

PMID- 23115595
TI  - Semi-supervised joint spatio-temporal feature selection for P300-based BCI
      speller.
AB  - In this paper, we address the important problem of feature selection for a P300
      based brain computer interface (BCI) speller system in several aspects. Firstly,
      time segment selection and electroencephalogram channel selection are jointly
      performed for better discriminability of P300 and background signals. Secondly,
      in view of the situation that training data with labels are insufficient, we
      propose an iterative semi-supervised support vector machine for joint spatio
      temporal feature selection as well as classification, in which both labeled
      training data and unlabeled test data are utilized. More importantly, the semi
      supervised learning enables the adaptivity of the system. The performance of our
      algorithm has been evaluated through the analysis of a P300 dataset provided by
      BCI Competition 2005 and another dataset collected from an in-house P300 speller
      system. The results show that our algorithm for joint feature selection and
      classification achieves satisfactory performance, meanwhile it can significantly
      reduce the training effort of the system. Furthermore, this algorithm is
      implemented online and the corresponding results demonstrate that our algorithm
      can improve the adaptiveness of the P300-based BCI speller.

PMID- 23115597
TI  - Virtual Screening for Finding Novel COX-2 Inhibitors as Antitumor Agents.
AB  - The cyclooxygenase-2 (COX-2) enzyme binds to arachidonic acid resulting in the
      release of metabolites that induce pain and inflammatory responses. Recent
      studies have shown that strong COX-2 expression is highly correlated with
      increased tumor risk. Therefore, the development of potent COX-2 inhibitors to
      relieve pain and treat cancers requires further investigation. We used virtual
      screening to find three COX-2 inhibitors (Phar-95239, T0511-4424 and Zu- 4280011)
      from a huge zinc database containing 2000000 compounds. The effects of the
      compounds on COX-2 were compared to those on COX-1 using a colorimetric COX
      (ovine) screening assay kit. The selectivity index, the ratio of IC(50) for COX-1
      inhibition to that of COX-2, calculated were MTT assay was used to evaluate the
      cytotoxic activity of the compounds using different dilutions. The IC(50) values
      were calculated. Based on the results of the MTT assay, the IC(50) values for
      compounds Phar-95239, T0511-4424 and Zu-4280011 were 178.52, 143 and 97.61 uM,
      respectively, and the selectivity indices of the compounds were 11.36, 12.20 and
      20.03, respectively. These results indicated a relationship between the
      selectivity index and anticancer activity. Zu-4280011 displayed the highest
      selectivity index and the best results in the MTT assay among selected componds.

PMID- 23115598
TI  - Use of an Injectable Complex of beta-Tricalcium Phosphate Granules, Hyaluronate,
      and Fibroblast Growth Factor-2 on Repair of Unstable Intertrochanteric Fractures.
AB  - We evaluated effects of an injectable complex of beta-tricalcium phosphate (beta
      TCP) granules, hyaluronate, and recombinant human fibroblast growth factor-2
      (rhFGF-2) on repair of unstable intertrochanteric fractures in elderly patients.
      Twenty-five patients (range, 76-91 years) having 31.A2 fractures (AO
      classification) were treated with injection of the complex followed by
      intramedullary nails. Bone regeneration and beta-TCP resorption, unions of
      intertrochanteric fractures and displaced lesser trochanters to the shaft, and
      varus deformity of the femoral neck were assessed by X-ray and CT scans. Fracture
      union occurred in all cases and union of the displaced lesser trochanter to the
      shaft was obtained in 24 cases by 12 weeks. It is of interest that beta-TCP
      granules were completely replaced by bone and marked new bone formation around
      the lesser trochanter was observed in all cases compared to cases not treated
      with the complex. This complex is a paste-like material that is easy to handle,
      and it may be of considerable use in treatment of both unstable intertrochanteric
      fractures and other cortical bone defects with minimal surgical invasion.

PMID- 23115599
TI  - Lung Injury in Asphyxiated Newborn Pigs Resuscitated from Cardiac Arrest - The
      Impact of Supplementary Oxygen, Longer Ventilation Intervals and Chest
      Compressions at Different Compression-to-Ventilation Ratios.
AB  - INTRODUCTION: Non-specific lung inflammatory events caused by severe asphyxia may
      be intensified by the way we resuscitate the newly born. Assessing lung injury is
      potentially important because if alternative resuscitation approaches induces
      similar inflammatory responses or less lung injury. then we may choose the
      resuscitation approach that is most gentle, and easiest to perform and learn. We
      investigated the levels of lung inflammatory markers by comparing different
      ventilation, chest compression and inhaled oxygen fraction strategies in
      resuscitation of newly born pigs at cardiac arrest. MATERIALS AND METHODOLOGY:
      Progressive asphyxia in newborn pigs was induced until asystole occurred. With
      current resuscitation guidelines as a reference group, pigs were randomized to
      receive initial ventilation before chest compressions for 30s, 60s or 90s, or to
      compression-to-ventilation ratios 3:1or 9:3, or to resuscitation using pure
      oxygen or air. We analysed inflammatory markers in bronchoalveolar lavage fluid
      (BAL), IL8 and TNFalpha, and lung tissue qPCR for genes matrix metalloproteinases
      (MMP)2, MMP9, TNFalpha and ICAM-1. RESULTS: BAL-levels of TNFalpha and IL8 tended
      to be higher in the 30s group compared to 60s group (p = 0.028 and p = 0.023,
      respectively) as was gene expression in lung tissue of ICAM-1 and MMP2 (p=0.012
      and p=0.043, respectively). MMP2 expression was slightly higher in the 30s group
      compared to 90s group (p = 0.020). No differences were found between pigs
      resuscitated with C:V ratio 9:3 and 3:1 or pure oxygen versus air. CONCLUSION:
      Compared to current guidelines, with respect to lung injury, resuscitation with
      longer initial ventilation should be considered. Longer series of chest
      compressions did not change the lung inflammatory response, neither did the use
      of air instead of pure oxygen in severely asphyxiated pigs resuscitated from
      asystole.

PMID- 23115600
TI  - Anxiety and depression symptoms in patients with sleep-disordered breathing.
AB  - INTRODUCTION: Information concerning the frequency of anxiety and depression
      symptoms in patients with sleep-disordered breathing (SDB) is controversial.
      Hence, the objectives of this study were to: determine the frequency of anxiety
      and depression symptoms in patients with SDB; explore whether the frequency of
      anxiety and depression symptoms rises with increasing parameters of SDB severity;
      and investigate the factors potentially associated with anxiety and depression.
      MATERIALS AND METHODOLOGY: Data was collected from consecutive adult patients
      referred to the National Institute of Respiratory Diseases' Sleep Medicine Unit
      from October 2008 to October 2009. SDB diagnoses were established using standard
      polysomnography or simplified respiratory polygraphy. All patients routinely
      completed the Hospital Anxiety and Depression Scale (HADS) on their first visit
      to the Sleep Medicine Unit. RESULTS: 382 patients with SDB were included. Mean
      age was 50.8+/-13.6 years, 62% were male. Anxiety symptoms were acknowledged by
      71 patients (18.5%), while 29 (7.6%) had depression symptoms, and 116 (30.4%) had
      symptoms of anxiety plus depression. Patients who reported anxiety and depression
      symptoms scored higher on the Epworth Sleepiness Scale (ESS, 16+/-7) than those
      with no symptoms (11+/-6) (p<0.0001). Patients with symptoms of anxiety plus
      depression also had higher BMIs (36 +/- 8 K/m(2)) than patients with SDB without
      anxiety or depression. No other differences were observed, not even with respect
      to the parameters of the severity of their SDB. CONCLUSIONS: Our results support
      the recommendation that due to their high frequency and potential importance for
      long-term adherence to CPAP, anxiety and depression symptoms should be included
      in the routine evaluation of all adults with SDB.

PMID- 23115601
TI  - Association Between Emphysema Score, Six-Minute Walk and Cardiopulmonary Exercise
      Tests in COPD.
AB  - BACKGROUND: High-resolution computed tomography (HRCT) has allowed in detection
      of airway wall abnormalities and emphysema, whose extent may correlate with the
      clinical severity of the disease in patients with chronic obstructive pulmonary
      disease (COPD). Six minute walk test (6MWT) and cardiopulmonary exercise test
      (CPET) can determine functional status. METHODS: A study was undertaken to
      investigate whether the extent of emphysema in COPD patients quantitatively
      confirmed by HRCT scoring was associated with distance walked, inspiratory
      capacity (IC) changes after exercise, anaerobic threshold of cardiopulmonary
      exercise and the BODE index (body mass index, airflow obstruction, dyspnea,
      exercise performance). RESULTS: Seventeen patients with COPD underwent HRCT
      scanning, 6MWT and CPET. The emphysema score was highly correlated to forced
      vital capacity (FVC) (r=-0.748, p<0.001), forced expiratory volume in 1 second
      (FEV1) (r=-0.615, p<0.01), IC post exercise (r=-0.663, p<0.01) and dyspnea score
      post exercise (r=0.609, p<0.01), but was not associated with the BODE index. The
      distance walked during 6MWT was inversely correlated to emphysema score (r=
      0.557, p<0.05). IC before exercise was highly related to the 6MWT. The change in
      IC after exercise was associated with the percent decline of oxygen saturation
      after exercise (r=0.633, p<0.01). Severity of lung emphysema in COPD patients was
      inversely correlated to VO(2) max (r=-0.514, p<0.05) and anaerobic threshold (r=
      0.595, p<0.01) of cardiopulmonary exercise. CONCLUSIONS: These results suggest
      that COPD associated with emphysema on HRCT is characterized by more severe lung
      function impairment, greater exercise impairment and cardiopulmonary dysfunction.

PMID- 23115602
TI  - The Effect of Stopping Smoking on Disease Activity in Rheumatoid Arthritis (RA).
      Data from BARFOT, a Multicenter Study of Early RA.
AB  - OBJECTIVE: We studied the effect of stopping smoking on disease activity in
      patients with RA. METHODS: Between 1992 and 2005, 2,800 adult patients were
      included in the BARFOT early RA study in Sweden. Disease Activity Score 28 joints
      (DAS28), C-reactive protein (CRP), Health Assessment Questionnaire (HAQ),
      rheumatoid factor (RF), anti-CCP, general health and pain visual analog scales
      (VAS), EULAR response and treatment were registered at inclusion and at follow-up
      2, 5 and 8 years. In 2010, a self-completion postal questionnaire was sent to
      2,102 patients, enquiring about lifestyle factors, including cessation of
      smoking. RESULTS: A total of 1,460 adult RA patients with disease duration <=2
      years were included in this study. Seventeen percent smoked in 2010. In total,
      127 patients stopped smoking after inclusion in the study. Smoking cessation
      after inclusion in the study was negatively associated with EULAR good outcome at
      8 years (OR 0.44, 95% CI 0.22-0.86, p=0.02), controlled for age, disease
      duration, sex, socioeconomic class, smoking status, RF, and DAS28 at inclusion.
      CONCLUSION: Seventeen percent of the RA patients smoked in 2010 in this large
      Swedish RA cohort. Stopping smoking after onset of RA did not change the poor
      prognosis of smokers with RA, but all RA patients need to stop smoking because of
      the high risk of cardiovascular mortality and morbidity and the association of
      smoking with vasculitis and noduli in RA.

PMID- 23115603
TI  - A survey of practice patterns for rehabilitation post elbow fracture.
AB  - BACKGROUND AND PURPOSE: Elbow fractures amount to 4.3% of all the fractures. The
      elbow is prone to stiffness after injury and fractures can often lead to
      significant functional impairment. Rehabilitation is commonly used to restore
      range of motion (ROM) and function. Practice patterns in elbow fracture
      rehabilitation have not been defined. The purpose of this study was to describe
      current elbow fracture rehabilitation practices; and compare those to the
      existing evidence base. METHODS: Hand therapists (n=315) from the USA (92%) and
      Canada (8%) completed a web-based survey on their practice patterns and beliefs
      related to the acute (0-6 weeks) and functional (6-12 weeks) phases of elbow
      fracture rehabilitation. RESULTS: More than 99% of respondents agreed that
      fracture severity, co-morbidities, time since fracture, compliance with an
      exercise program, psychological factors, and occupational demands are important
      prognostic indicators for optimal function. Strong agreement was found with the
      use of patient education (95%) and active ROM (86%) in the acute stage while,
      home exercise programs (99%), active ROM (99%), stretching (97%), strengthening
      (97%), functional activities (ADLs and routine tasks) (97%), passive ROM (95%),
      and active assisted ROM (95%) were generally used in the functional stage. The
      most commonly used impairment measures were goniometry (99%), Jamar dynamometry
      (97%), and hand held dynamometry (97%). Agreement on the use of patient-reported
      outcome measures was very minimal (1.3%- 35.6%). CONCLUSIONS: Exercise,
      education, and functional activity have high consensus as components of elbo
      fracture rehabilitation. Future research should focus on defining the optimal
      dosage and type of exercise/activity, and establish core measures to monitor
      outcomes of these interventions.

PMID- 23115604
TI  - Prevalence of known and unknown primary tumor sites in spinal metastasis
      patients.
AB  - STUDY DESIGN: A retrospective study. OBJECTIVES: THREE OBJECTIVES HAVE BEEN
      DESIGNATED FOR THIS STUDY: (1) to determine the prevalence of identifiable and
      non-identifiable primary tumor sites in patients with spinal metastasis, (2) to
      identify the most common site of the known primary tumor sites, and (3) to
      identify the factors associated with survival time. SUMMARY OF BACKGROUND DATA:
      The spine is the third most common metastatic site for several primary visceral
      carcinomas. The primary tumor site could not be identified in 15% to 20% of
      patients who had been diagnosed of with a skeletal metastasis. Most of the
      previous studies on skeletal metastasis have not been limited to spinal
      metastasis alone. METHODS: Between January 2007 and July 2011 reviews were done
      for 82 patients with spinal metastasis who had not received a previous diagnosis
      of carcinoma. The assessment parameters included the following: general
      demographic data, Karnofsky score, Frankel score, number of spinal vertebra
      affected, region of the spine affected by metastasis, other skeletal metastasis
      site, visceral metastasis, known or unknown primary sites of metastasis,
      histological cell type of metastasis, and the survival period. The log-rank test
      and Cox proportional hazard model were used to study the survival analysis.
      RESULTS: Of the 82 patients included in the study, 56 were male. The mean age was
      57 years. 86.6% had a known primary carcinoma site while the remaining 13.4% had
      none. The two most common known carcinoma sites were the lung and biliary
      systems. Among the 11 unknown primary sites, the most common histological finding
      was adenocarcinoma. The mean survival period was 8.7 +/- 11.7 months. The
      survival analysis revealed two statistically significant factors: the primary
      tumor site's aggressiveness (P<0.005) and the presence of visceral metastasis
      (P<0.05). CONCLUSION: The prevalence of identifiable primary site was 86.6% and
      the most common site was the lungs followed by the biliary system. The primary
      carcinoma site's aggressiveness and the presence of visceral metastasis were the
      factors associated with patient survival.

PMID- 23115605
TI  - Glucocorticoid-induced avascular bone necrosis: diagnosis and management.
AB  - Glucocorticoid use is one of the most important causes of avascular bone necrosis
      (AVN). The pathogenesis of glucocorticoid-induced AVN is not fully understood but
      postulated mechanisms include fat hypertrophy, fat emboli and intravascular
      coagulation that cause impedance of blood supply to the bones. Data regarding the
      relationship between AVN and dosage, route of administration and treatment
      duration of glucocorticoids are conflicting, with some studies demonstrating the
      cumulative dose of glucocorticoid being the most important determining factor.
      Early recognition of this complication is essential as the prognosis is affected
      by the stage of the disease. Currently, there is no consensus on whether
      universal screening of asymptomatic AVN should be performed for long-term
      glucocorticoid users. A high index of suspicion should be exhibited for bone and
      joint pain at typical sites. Magnetic resonance imaging (MRI) or bone
      scintigraphy is more sensitive than plain radiograph for diagnosing early-stage
      AVN. Conservative management of AVN includes rest and reduction of weight
      bearing. Minimization of glucocorticoid dose or a complete withdrawal of the drug
      should be considered if the underlying conditions allow. The efficacy of
      bisphosphonates in reducing the rate of collapse of femoral head in AVN is
      controversial. Surgical therapy of AVN includes core decompression, osteotomy,
      bone grafting and joint replacement. Recent advances in the treatment of AVN
      include the use of tantalum rod and the development of more wear resistant
      bearing surface in hip arthroplasty.

PMID- 23115606
TI  - Relationship between mechanical properties and bone mineral density of human
      femoral bone retrieved from patients with osteoarthritis.
AB  - The objective of this study was to analyse retrieved human femoral bone samples
      using three different test methods, to elucidate the relationship between bone
      mineral density and mechanical properties. Human femoral heads were retrieved
      from 22 donors undergoing primary total hip replacement due to hip osteoarthritis
      and stored for a maximum of 24 hours postoperatively at + 6  degrees C to 8 
      degrees C.Analysis revealed an average structural modulus of 232+/-130 N/mm(2)
      and ultimate compression strength of 6.1+/-3.3 N/mm(2) with high standard
      deviations. Bone mineral densities of 385+/-133 mg/cm(2) and 353+/-172 mg/cm(3)
      were measured using thedual energy X-ray absorptiometry (DXA) and quantitative
      computed tomography (QCT), respectively. Ashing resulted in a bone mineral
      density of 323+/-97 mg/cm(3). In particular, significant linear correlations were
      found between DXA and ashing with r = 0.89 (p < 0.01, n = 22) and between
      structural modulus and ashing with r = 0.76 (p < 0.01, n = 22).Thus, we
      demonstrated a significant relationship between mechanical properties and bone
      density. The correlations found can help to determine the mechanical load
      capacity of individual patients undergoing surgical treatments by means of
      noninvasive bone density measurements.

PMID- 23115607
TI  - Factors Associated with Lifetime HIV Testing in Texas by Race/Ethnicity.
AB  - INTRODUCTION: In United States, roughly 1/5 of all HIV infected persons remain
      undiagnosed. Because HIV testing is critical to improve prevention efforts, more
      research is needed to understand the characteristics of individuals who get
      tested for HIV. METHODS: This secondary analysis of the 2010 Texas Behavioral
      Risk Factor Surveillance System used data from 9,744 respondents between 18-64
      years of age to evaluate the relationship between demographic characteristics
      (gender, race/ethnicity, age, area of residence, education, marital status,
      employment status, and income), healthcare characteristics (insurance status,
      having a primary provider, and access to healthcare), and HIV risk behaviors with
      ever having received an HIV test. RESULTS: Significant associations between
      gender, age, area of residence, marital and employment status, and HIV risk
      behaviors and HIV testing in a Texas population by race/ethnicity were observed.
      CONCLUSIONS: These findings have important implications for future research into
      racial/ethnic disparities between lifetime HIV testing, and can help guide
      practitioners who work with populations at risk for HIV/AIDS in Texas.

PMID- 23115608
TI  - Expression of CCR5, CXCR4 and DC-SIGN in Cervix of HIV-1 Heterosexually Infected
      Mexican Women.
AB  - BACKGROUND: A number of studies have demonstrated that receptor and co-receptor
      expression levels which may affect viral entry, promoting cervical HIV infection.
      The aim was to evaluate the expression levels of CCR5, CXCR4and DC-SIGN mRNA in a
      sample of heterosexually HIV infected Mexican women. METHODS: We enrolled twenty
      six HIV heterosexual infected women attending a local infectious diseases medical
      unit.RNA was isolated from the cervix and gene expression analysis was performed
      using real-time PCR. RESULTS: Expression rates for mRNA of CCR5 (median 1.82;
      range 0.003-2934) were higher than those observed for CXCR4 (0.79; 0.0061-3312)
      and DC-SIGN (0.33; 0.006-532) receptors (p < 0.05). A high correlation was found
      between the mRNA expression levels of these three receptors (rs = 0.52 to 0.85, p
      < 0.01). CONCLUSION: Levels of expression of the tested chemokine receptors in
      the cervix are different from each other and alsovary from woman to woman, and
      seem to support the suggestion that chemokine receptor expression in genital
      tissues may be playing a role in the HIV transmission.

PMID- 23115609
TI  - HaloTag(r) Platform: From Proteomics to Cellular Analysis and Animal Imaging.

PMID- 23115610
TI  - The HaloTag: Improving Soluble Expression and Applications in Protein Functional
      Analysis.
AB  - Technological and methodological advances have been critical for the rapidly
      evolving field of proteomics. The development of fusion tag systems is essential
      for purification and analysis of recombinant proteins. The HaloTag is a 34 KDa
      monomeric protein derived from a bacterial haloalkane dehalogenase. The majority
      of fusion tags in use today utilize a reversible binding interaction with a
      specific ligand. The HaloTag system is unique in that it forms a covalent linkage
      to its chloroalkane ligand. This linkage permits attachment of the HaloTag to a
      variety of functional reporters, which can be used to label and immobilize
      recombinant proteins. The success rate for HaloTag expression of soluble proteins
      is very high and comparable to maltose binding protein (MBP) tag. Furthermore,
      cleavage of the HaloTag does not result in protein insolubility that often is
      observed with the MBP tag. In the present report, we describe applications of the
      HaloTag system in our ongoing investigation of protein-protein interactions of
      the Y. pestis Type 3 secretion system on a custom protein microarray. We also
      describe the utilization of affinity purification/mass spectroscopy (AP/MS) to
      evaluate the utility of the Halo Tag system to characterize DNA binding activity
      and protein specificity.

PMID- 23115611
TI  - Galectin-1 and Galectin-3 Mediate Protocadherin-24-Dependent Membrane
      Localization of beta-catenin in Colon Cancer Cell Line HCT116.
AB  - Protocadherin-24 (PCDH24) is linked to the suppression of tumor growth and the
      inhibition of cell proliferation in the colon cancer cell line HCT116. We
      previously observed that beta-catenin is localized to the plasma membrane when
      PCDH24 is expressed in these cells, but the molecular mechanisms by which PCDH24
      induces the membrane localization of beta-catenin remain largely unknown. To
      clarify these mechanisms, we identified molecules that interact with ectopically
      expressed PCDH24 in HCT116 cells using a HaloTag(r) pull-down assay. We found
      that galectin-1 and galectin-3 physically interact with PCDH24 and are retained
      at the plasma membrane in association with PCDH24 expression. A luciferase-based
      pull-down assay using HaloTag-fused galectins revealed that an intracellular
      region of PCDH24 (amino acids 1186-1280) is essential for this interaction.
      Furthermore, the over-expression of galectin-1 or -3, or the depletion of
      endogenous galectins by small interfering RNA modulates beta-catenin
      translocation. We also revealed that the retention of galectin-1 and -3 at the
      plasma membrane results in the inactivation of PI3K activity. From these
      findings, we propose a model in which the galectin-anchoring activity of PCDH24
      leads to the suppression of beta-catenin signaling by the localization of beta
      catenin at the plasma membrane in PCDH24-expressing HCT116 colon cancer cells.

PMID- 23115612
TI  - Utilizing HaloTag Technology to Track the Fate of PCSK9 from Intracellular vs.
      Extracellular Sources.
AB  - The function of a particular protein is dependent upon its localization and
      milieu. The ability to track the "fate" of a protein is a valuable tool to
      elucidate its function. We present the use of HaloTag technology to study the
      localization and fate of human Proprotein Convertase Subtilisin-like Kexin type 9
      (PCSK9).The role of PCSK9 in the regulation of circulating low density
      lipoprotein-cholesterol (LDL-c) levels is ascribed to binding of circulating
      PCSK9 to the LDL receptor (LDLR) and subsequent lysosomal degradation of LDLR.
      However, hints in the literature indicate that intracellular PCSK9 may act on the
      LDLR, possibly during processing of newly synthesized protein. To address this
      question, the source and fate of intracellular PCSK9 requires further
      investigation.We applied HaloTag technology to distinguish the source of
      intracellular PCSK9 and showed that newly synthesized intracellular PCSK9 has
      unique localization from the PCSK9 after re-uptake. This suggests different
      functions of PCSK9 while interacting with the LDLR.

PMID- 23115613
TI  - In Vivo Fluorescent Labeling of Tumor Cells with the HaloTag(r) Technology.
AB  - Many fluorescent sensors are currently available for in vitro bio-physiological
      microscopic imaging. The ability to label cells in living animals with these
      fluorescent sensors would help translate some of these assays into in vivo
      applications. To achieve this goal, the first step is to establish a method for
      selectively labeling target cells with exogenous fluorophores. Here we tested
      whether the HaloTag(r) protein tagging system provides specific labeling of
      xenograft tumors in living animals. After systemic delivery of fluorophore
      conjugated ligands, we performed whole animal planar fluorescent imaging to
      determine uptake in tag-expressing HCT116 xenografts. Our results demonstrate
      that HaloTag ligands containing red or near-infrared fluorophores have enhanced
      tumor uptake and are suitable for non-invasive in vivo imaging. Our proof-of
      concept results establish feasibility for using HaloTag technology for bio
      physiological imaging in living animals.

PMID- 23115614
TI  - mRNA expression in papillary and anaplastic thyroid carcinoma: molecular anatomy
      of a killing switch.
AB  - Anaplastic thyroid carcinoma (ATC) is the most lethal form of thyroid neoplasia
      and represents the end stage of thyroid tumor progression. No effective treatment
      exists so far. ATC frequently derive from papillary thyroid carcinomas (PTC),
      which have a good prognosis. In this study, we analyzed the mRNA expression
      profiles of 59 thyroid tumors (11 ATC and 48 PTC) by microarrays. ATC and PTC
      showed largely overlapping mRNA expression profiles with most genes regulated in
      all ATC being also regulated in several PTC. 43% of the probes regulated in all
      the PTC are similarly regulated in all ATC. Many genes modulations observed in
      PTC are amplified in ATC. This illustrates the fact that ATC mostly derived from
      PTC. A molecular signature of aggressiveness composed of 9 genes clearly
      separates the two tumors. Moreover, this study demonstrates gene regulations
      corresponding to the ATC or PTC phenotypes like inflammatory reaction, epithelial
      to mesenchymal transition (EMT) and invasion, high proliferation rate,
      dedifferentiation, calcification and fibrosis processes, high glucose metabolism
      and glycolysis, lactate generation and chemoresistance. The main qualitative
      differences between the two tumor types bear on the much stronger EMT,
      dedifferentiation and glycolytic phenotypes showed by the ATC.

PMID- 23115615
TI  - Taurine provides neuroprotection against retinal ganglion cell degeneration.
AB  - Retinal ganglion cell (RGC) degeneration occurs in numerous retinal diseases
      leading to blindness, either as a primary process like in glaucoma, or secondary
      to photoreceptor loss. However, no commercial drug is yet directly targeting RGCs
      for their neuroprotection. In the 70s, taurine, a small sulfonic acid provided by
      nutrition, was found to be essential for the survival of photoreceptors, but this
      dependence was not related to any retinal disease. More recently, taurine
      deprivation was incriminated in the retinal toxicity of an antiepileptic drug. We
      demonstrate here that taurine can improve RGC survival in culture or in different
      animal models of RGC degeneration. Taurine effect on RGC survival was assessed in
      vitro on primary pure RCG cultures under serum-deprivation conditions, and on
      NMDA-treated retinal explants from adult rats. In vivo, taurine was administered
      through the drinking water in two glaucomatous animal models (DBA/2J mice and
      rats with vein occlusion) and in a model of Retinitis pigmentosa with secondary
      RGC degeneration (P23H rats). After a 6-day incubation, 1 mM taurine
      significantly enhanced RGCs survival (+68%), whereas control RGCs were cultured
      in a taurine-free medium, containing all natural amino-acids. This effect was
      found to rely on taurine-uptake by RGCs. Furthermore taurine (1 mM) partly
      prevented NMDA-induced RGC excitotoxicity. Finally, taurine supplementation
      increased RGC densities both in DBA/2J mice, in rats with vein occlusion and in
      P23H rats by contrast to controls drinking taurine-free water. This study
      indicates that enriched taurine nutrition can directly promote RGC survival
      through RGC intracellular pathways. It provides evidence that taurine can
      positively interfere with retinal degenerative diseases.

PMID- 23115616
TI  - Transcription of liver X receptor is down-regulated by 15-deoxy-Delta(12,14)
      prostaglandin J(2) through oxidative stress in human neutrophils.
AB  - Liver X receptors (LXRs) are ligand-activated transcription factors of the
      nuclear receptor superfamily. They play important roles in controlling
      cholesterol homeostasis and as regulators of inflammatory gene expression and
      innate immunity, by blunting the induction of classical pro-inflammatory genes.
      However, opposite data have also been reported on the consequences of LXR
      activation by oxysterols, resulting in the specific production of potent pro
      inflammatory cytokines and reactive oxygen species (ROS). The effect of the
      inflammatory state on the expression of LXRs has not been studied in human cells,
      and constitutes the main aim of the present work. Our data show that when human
      neutrophils are triggered with synthetic ligands, the synthesis of LXRalpha mRNA
      became activated together with transcription of the LXR target genes ABCA1, ABCG1
      and SREBP1c. An inflammatory mediator, 15-deoxy-Delta(12,14)-prostaglandin J(2)
      (15dPGJ(2)), hindered T0901317-promoted induction of LXRalpha mRNA expression
      together with transcription of its target genes in both neutrophils and human
      macrophages. This down-regulatory effect was dependent on the release of reactive
      oxygen species elicited by 15dPGJ(2), since it was enhanced by pro-oxidant
      treatment and reversed by antioxidants, and was also mediated by ERK1/2
      activation. Present data also support that the 15dPGJ(2)-induced serine
      phosphorylation of the LXRalpha molecule is mediated by ERK1/2. These results
      allow to postulate that down-regulation of LXR cellular levels by pro
      inflammatory stimuli might be involved in the development of different vascular
      diseases, such as atherosclerosis.

PMID- 23115617
TI  - A comprehensive survey of retracted articles from the scholarly literature.
AB  - BACKGROUND: The number of retracted scholarly articles has risen precipitously in
      recent years. Past surveys of the retracted literature each limited their scope
      to articles in PubMed, though many retracted articles are not indexed in PubMed.
      To understand the scope and characteristics of retracted articles across the full
      spectrum of scholarly disciplines, we surveyed 42 of the largest bibliographic
      databases for major scholarly fields and publisher websites to identify retracted
      articles. This study examines various trends among them. RESULTS: We found, 4,449
      scholarly publications retracted from 1928-2011. Unlike Math, Physics,
      Engineering and Social Sciences, the percentages of retractions in Medicine, Life
      Science and Chemistry exceeded their percentages among Web of Science (WoS)
      records. Retractions due to alleged publishing misconduct (47%) outnumbered those
      due to alleged research misconduct (20%) or questionable data/interpretations
      (42%). This total exceeds 100% since multiple justifications were listed in some
      retraction notices. Retraction/WoS record ratios vary among author affiliation
      countries. Though widespread, only miniscule percentages of publications for
      individual years, countries, journals, or disciplines have been retracted.
      Fifteen prolific individuals accounted for more than half of all retractions due
      to alleged research misconduct, and strongly influenced all retraction
      characteristics. The number of articles retracted per year increased by a factor
      of 19.06 from 2001 to 2010, though excluding repeat offenders and adjusting for
      growth of the published literature decreases it to a factor of 11.36.
      CONCLUSIONS: Retracted articles occur across the full spectrum of scholarly
      disciplines. Most retracted articles do not contain flawed data; and the authors
      of most retracted articles have not been accused of research misconduct. Despite
      recent increases, the proportion of published scholarly literature affected by
      retraction remains very small. Articles and editorials discussing retractions, or
      their relation to research integrity, should always consider individual cases in
      these broad contexts. However, better mechanisms are still needed for raising
      researchers' awareness of the retracted literature in their field.

PMID- 23115618
TI  - In vivo functional requirement of the mouse Ifitm1 gene for germ cell
      development, interferon mediated immune response and somitogenesis.
AB  - The mammalian Interferon induced transmembrane protein 1 (Ifitm1) gene was
      originally identified as a member of a gene family highly inducible by type I and
      type II interferons. Based on expression analyses, it was suggested to be
      required for normal primordial germ cell migration. The knockdown of Ifitm1 in
      mouse embryos provided evidence for a role in somitogenesis. We generated the
      first targeted knockin allele of the Ifitm1 gene to systematically reassess all
      inferred functions. Sperm motility and the fertility of male and female mutant
      mice are as in wild type littermates. Embryonic somites and the adult vertebral
      column appear normal in homozygous Ifitm1 knockout mice, demonstrating that
      Ifitm1 is not essential for normal segmentation of the paraxial mesoderm.
      Proportions of leucocyte subsets, including granulocytes, monocytes, B-cells, T
      cells, NK-cells, and NKT-cells, are unchanged in mutant mice. Based on a normal
      immune response to Listeria monocytogenes infection, there is no evidence for a
      dysfunction in downstream IFNgamma signaling in Ifitm1 mutant mice. Expression
      from the Ifitm1 locus from E8.5 to E14.5 is highly dynamic. In contrast, in adult
      mice, Ifitm1 expression is highly restricted and strong in the bronchial
      epithelium. Intriguingly, IFITM1 is highly overexpressed in tumor epithelia cells
      of human squamous cell carcinomas and in adenocarcinomas of NSCLC patients. These
      analyses underline the general importance of targeted in vivo studies for the
      functional annotation of the mammalian genome. The first comprehensive
      description of the Ifitm1 expression pattern provides a rational basis for the
      further examination of Ifitm1 gene functions. Based on our data, the fact that
      IFITM1 can function as a negative regulator of cell proliferation, and because
      the gene maps to chromosome band 11p15.5, previously associated with NSCLC, it is
      likely that IFITM1 in man has a key role in tumor formation.

PMID- 23115619
TI  - Novel targets of the CbrAB/Crc carbon catabolite control system revealed by
      transcript abundance in Pseudomonas aeruginosa.
AB  - The opportunistic human pathogen Pseudomonas aeruginosa is able to utilize a wide
      range of carbon and nitrogen compounds, allowing it to grow in vastly different
      environments. The uptake and catabolism of growth substrates are organized
      hierarchically by a mechanism termed catabolite repression control (Crc) whereby
      the Crc protein establishes translational repression of target mRNAs at CA
      (catabolite activity) motifs present in target mRNAs near ribosome binding sites.
      Poor carbon sources lead to activation of the CbrAB two-component system, which
      induces transcription of the small RNA (sRNA) CrcZ. This sRNA relieves Crc
      mediated repression of target mRNAs. In this study, we have identified novel
      targets of the CbrAB/Crc system in P. aeruginosa using transcriptome analysis in
      combination with a search for CA motifs. We characterized four target genes
      involved in the uptake and utilization of less preferred carbon sources: estA
      (secreted esterase), acsA (acetyl-CoA synthetase), bkdR (regulator of branched
      chain amino acid catabolism) and aroP2 (aromatic amino acid uptake protein).
      Evidence for regulation by CbrAB, CrcZ and Crc was obtained in vivo using
      appropriate reporter fusions, in which mutation of the CA motif resulted in loss
      of catabolite repression. CbrB and CrcZ were important for growth of P.
      aeruginosa in cystic fibrosis (CF) sputum medium, suggesting that the CbrAB/Crc
      system may act as an important regulator during chronic infection of the CF lung.

PMID- 23115620
TI  - Biases and power for groups comparison on subjective health measurements.
AB  - Subjective health measurements are increasingly used in clinical research,
      particularly for patient groups comparisons. Two main types of analytical
      strategies can be used for such data: so-called classical test theory (CTT),
      relying on observed scores and models coming from Item Response Theory (IRT)
      relying on a response model relating the items responses to a latent parameter,
      often called latent trait. Whether IRT or CTT would be the most appropriate
      method to compare two independent groups of patients on a patient reported
      outcomes measurement remains unknown and was investigated using simulations. For
      CTT-based analyses, groups comparison was performed using t-test on the scores.
      For IRT-based analyses, several methods were compared, according to whether the
      Rasch model was considered with random effects or with fixed effects, and the
      group effect was included as a covariate or not. Individual latent traits values
      were estimated using either a deterministic method or by stochastic approaches.
      Latent traits were then compared with a t-test. Finally, a two-steps method was
      performed to compare the latent trait distributions, and a Wald test was
      performed to test the group effect in the Rasch model including group covariates.
      The only unbiased IRT-based method was the group covariate Wald's test, performed
      on the random effects Rasch model. This model displayed the highest observed
      power, which was similar to the power using the score t-test. These results need
      to be extended to the case frequently encountered in practice where data are
      missing and possibly informative.

PMID- 23115621
TI  - Reasons for receiving or not receiving HPV vaccination in primary schoolgirls in
      Tanzania: a case control study.
AB  - BACKGROUND: There are few data on factors influencing human papillomavirus (HPV)
      vaccination uptake in sub-Saharan Africa. We examined the characteristics of
      receivers and non-receivers of HPV vaccination in Tanzania and identified reasons
      for not receiving the vaccine. METHODS: We conducted a case control study of HPV
      vaccine receivers and non-receivers within a phase IV cluster-randomised trial of
      HPV vaccination in 134 primary schools in Tanzania. Girls who failed to receive
      vaccine (pupil cases) and their parents/guardians (adult cases) and girls who
      received dose 1 (pupil controls) of the quadrivalent vaccine (GardasilTM) and
      their parents/guardians (adult controls) were enrolled from 39 schools in a 1?1
      ratio and interviewed about cervical cancer, HPV vaccine knowledge and reasons
      why they might have received or not received the vaccine. Conditional logistic
      regression was used to determine factors independently associated with not
      receiving HPV vaccine. RESULTS: We interviewed 159 pupil/adult cases and 245
      pupil/adult controls. Adult-factors independently associated with a daughter
      being a case were older age, owning fewer household items, not attending a school
      meeting about HPV vaccine, and not knowing anyone with cancer. Pupil-factors for
      being a case included having a non-positive opinion about the school de-worming
      programme, poor knowledge about the location of the cervix, and not knowing that
      a vaccine could prevent cervical cancer. Reasons for actively refusing
      vaccination included concerns about side effects and infertility. Most adult and
      pupil cases reported that they would accept the HPV vaccine if it were offered
      again (97% and 93% respectively). CONCLUSIONS: Sensitisation messages, especially
      targeted at older and poorer parents, knowledge retention and parent meetings are
      critical for vaccine acceptance in Tanzania. Vaccine side effects and fertility
      concerns should be addressed prior to a national vaccination program. Parents and
      pupils who initially decline vaccination should be given an opportunity to
      reconsider their decision.

PMID- 23115622
TI  - Speech perception and localisation with SCORE bimodal: a loudness normalisation
      strategy for combined cochlear implant and hearing aid stimulation.
AB  - A significant fraction of newly implanted cochlear implant recipients use a
      hearing aid in their non-implanted ear. SCORE bimodal is a sound processing
      strategy developed for this configuration, aimed at normalising loudness
      perception and improving binaural loudness balance. Speech perception performance
      in quiet and noise and sound localisation ability of six bimodal listeners were
      measured with and without application of SCORE. Speech perception in quiet was
      measured either with only acoustic, only electric, or bimodal stimulation, at
      soft and normal conversational levels. For speech in quiet there was a
      significant improvement with application of SCORE. Speech perception in noise was
      measured for either steady-state noise, fluctuating noise, or a competing talker,
      at conversational levels with bimodal stimulation. For speech in noise there was
      no significant effect of application of SCORE. Modelling of interaural loudness
      differences in a long-term-average-speech-spectrum-weighted click train indicated
      that left-right discrimination of sound sources can improve with application of
      SCORE. As SCORE was found to leave speech perception unaffected or to improve it,
      it seems suitable for implementation in clinical devices.

PMID- 23115623
TI  - Residual tumor cells that drive disease relapse after chemotherapy do not have
      enhanced tumor initiating capacity.
AB  - Although chemotherapy is used to treat most advanced solid tumors, recurrent
      disease is still the major cause of cancer-related mortality. Cancer stem cells
      (CSCs) have been the focus of intense research in recent years because they
      provide a possible explanation for disease relapse. However, the precise role of
      CSCs in recurrent disease remains poorly understood and surprisingly little
      attention has been focused on studying the cells responsible for re-initiating
      tumor growth within the original host after chemotherapy treatment. We utilized
      both xenograft and genetically engineered mouse models of non-small cell lung
      cancer (NSCLC) to characterize the residual tumor cells that survive chemotherapy
      treatment and go on to cause tumor regrowth, which we refer to as tumor re
      initiating cells (TRICs). We set out to determine whether TRICs display
      characteristics of CSCs, and whether assays used to define CSCs also provide an
      accurate readout of a cell's ability to cause tumor recurrence. We did not find
      consistent enrichment of CSC marker positive cells or enhanced tumor initiating
      potential in TRICs. However, TRICs from all models do appear to be in EMT, a
      state that has been linked to chemoresistance in numerous types of cancer. Thus,
      the standard CSC assays may not accurately reflect a cell's ability to drive
      disease recurrence.

PMID- 23115624
TI  - Demographic amplification of climate change experienced by the contiguous United
      States population during the 20(th) century.
AB  - Better understanding of the changing relationship between human populations and
      climate is a global research priority. The 20(th) century in the contiguous
      United States offers a particularly well-documented example of human demographic
      expansion during a period of radical socioeconomic and environmental change. One
      would expect that as human society has been transformed by technology, we would
      become increasingly decoupled from climate and more dependent on social
      infrastructure. Here we use spatially-explicit models to evaluate climatic, socio
      economic and biophysical correlates of demographic change in the contiguous
      United States between 1900 and 2000. Climate-correlated variation in population
      growth has caused the U.S. population to shift its realized climate niche from
      cool, seasonal climates to warm, aseasonal climates. As a result, the average
      annual temperature experienced by U.S. citizens between 1920 and 2000 has
      increased by more than 1.5 degrees C and the temperature seasonality has
      decreased by 1.1 degrees C during a century when climate change accounted for
      only a 0.24 degrees C increase in average annual temperature and a 0.15 degrees C
      decrease in temperature seasonality. Thus, despite advancing technology, climate
      correlated demographics continue to be a major feature of contemporary U.S.
      society. Unfortunately, these demographic patterns are contributing to a
      substantial warming of the climate niche during a period of rapid environmental
      warming, making an already bad situation worse.

PMID- 23115625
TI  - Fragment-hopping-based discovery of a novel chemical series of proto-oncogene PIM
      1 kinase inhibitors.
AB  - A new chemical series, triazolo[4,5-b]pyridines, has been identified as an
      inhibitor of PIM-1 by a chemotype hopping strategy based on a chemically feasible
      fragment database. In this case, structure-based virtual screening and in silico
      chemogenomics provide added value to the previously reported strategy of
      prioritizing among proposed novel scaffolds. Pairwise comparison between compound
      3, recently discontinued from Phase I clinical trials, and molecule 8, bearing
      the selected novel scaffold, shows that the primary activities are similar
      (IC(50) in the 20 to 150 nM range). At the same time, some ADME properties (for
      example, an increase of more than 45% in metabolic stability in human liver
      microsomes) and the off-target selectivity (for example, an increase of more than
      2 log units in IC(50)vs. FLT3) are improved, and the intellectual property (IP)
      position is enhanced. The discovery of a reliable starting point that fulfills
      critical criteria for a plausible medicinal chemistry project is demonstrated in
      this prospective study.

PMID- 23115626
TI  - Structure and activity analysis of Inauhzin analogs as novel antitumor compounds
      that induce p53 and inhibit cell growth.
AB  - Identifying effective small molecules that specifically target the p53 pathway in
      cancer has been an exciting, though challenging, approach for the development of
      anti-cancer therapy. We recently identified Inauhzin (INZ) as a novel p53
      activator, selectively and efficiently suppressing tumor growth without
      displaying genotoxicity and with little toxicity to normal cells. In order to
      reveal the structural features essential for anti-cancer activity of this small
      molecule, we have synthesized a panel of INZ analogs and evaluated their ability
      to induce cellular p53 and to inhibit cell growth in cell-based assays. This
      study as described here leads to the discovery of INZ analog 37 that displays
      much better potency than INZ in both of p53 activation and cell growth inhibition
      in several human cancer cell lines including H460 and HCT116(+/+) cells. This INZ
      analog exhibited much less effect on p53-null H1299 cells and HCT116(-/-) cells,
      and importantly no toxicity on normal human p53-containing WI-38 cells. Hence,
      our results not only unveil key chemical features for INZ activity, but also
      identify the newly synthesized INZ analog 37 as a better small molecule for
      further development of anti-cancer therapy.

PMID- 23115627
TI  - Persistent catheter-related Staphylococcus aureus bacteremia after catheter
      removal and initiation of antimicrobial therapy.
AB  - OBJECTIVES: Catheter-related Staphylococcus aureus bacteremia (CRSAB)
      occasionally persists despite catheter removal and initiation of appropriate
      antimicrobial therapy. The aim of this study was to determine the incidence, risk
      factors, and outcomes of persistent CRSAB after catheter removal and initiation
      of antimicrobial therapy. METHODS: Consecutive patients with CRSAB were
      prospectively included from over a 41-month period. We compared the clinical
      features, 40 bacterial virulence genes, and outcomes between patients with
      persistent CRSAB (i.e., bacteremia for >3 days after catheter removal and
      initiation of appropriate antimicrobial therapy) and non-persistent CRSAB.
      RESULTS: Among the 220 episodes of CRSAB, the catheter was kept in place in 17
      (6%) and removed in 203 (94%) cases. In 43 (21%) of the 203 episodes, bacteremia
      persisted for >3 days after catheter removal and initiation of antimicrobial
      therapy. Methicillin resistance (Odds ratio [OR], 9.01; 95% confidence interval
      [CI], 3.05-26.61; P<0.001), non-catheter prosthetic devices (OR, 5.37; 95% CI,
      1.62-17.80; P=0.006), and renal failure (OR, 3.23; 95% CI, 1.48-7.08; P=0.003)
      were independently associated with persistent CRSAB. Patients with persistent
      CRSAB were more like to experience complication than were those with non
      persistent CRSAB (72% vs. 15%; P<0.001). Among all episodes due to methicillin
      resistant S. aureus, persistent CRSAB isolates were associated with accessory
      gene regulator (agr) group II (P= .04), but presence of other bacterial virulence
      genes, distribution of vancomycin minimum inhibitory concentration distribution,
      and frequency of vancomycin heteroresistance did not differ between the groups.
      CONCLUSIONS: In patients with CRSAB, bacteremia persisted in 21% of cases despite
      catheter removal and initiation of antimicrobial therapy. Methicillin resistance,
      renal failure, and non-catheter prosthetic devices were independent risk factors
      for persistent CRSAB, which was associated with a higher rate of complications.

PMID- 23115628
TI  - A novel educational strategy targeting health care workers in underserved
      communities in Central America to integrate HIV into primary medical care.
AB  - BACKGROUND: Current educational strategies to integrate HIV care into primary
      medical care in Central America have traditionally targeted managers or higher
      level officials, rather than local health care workers (HCWs). We developed a
      complementary online and on-site interactive training program to reach local HCWs
      at the primary care level in underserved communities. METHODS: The training
      program targeted physicians, nurses, and community HCWs with limited access to
      traditional onsite training in Panama, Nicaragua, Dominican Republic, and
      Guatemala. The curriculum focused on principles of HIV care and health systems
      using a tutor-supported blended educational approach of an 8-week online
      component, a weeklong on-site problem-solving workshop, and individualized
      project-based interventions. RESULTS: Of 258 initially active participants, 225
      (225/258=87.2%) successfully completed the online component and the top 200 were
      invited to the on-site workshop. Of those, 170 (170/200=85%) attended the on-site
      workshop. In total, 142 completed all three components, including the project
      phase. Quantitative and qualitative evaluation instruments included knowledge
      assessments, reflexive essays, and acceptability surveys. The mean pre and post
      essay scores demonstrating understanding of social determinants, health system
      organization, and integration of HIV services were 70% and 87.5%, respectively,
      with an increase in knowledge of 17.2% (p<0.001). The mean pre- and post-test
      scores evaluating clinical knowledge were 70.9% and 90.3%, respectively, with an
      increase in knowledge of 19.4% (p<0.001). A survey of Likert scale and open-ended
      questions demonstrated overwhelming participant satisfaction with course content,
      structure, and effectiveness in improving their HIV-related knowledge and skills.
      CONCLUSION: This innovative curriculum utilized technology to target HCWs with
      limited access to educational resources. Participants benefited from technical
      skills acquired through the process, and could continue working within their
      underserved communities while participating in the online component and then
      implement interventions that successfully converted theoretical knowledge to
      action to improve integration of HIV care into primary care.

PMID- 23115629
TI  - Inferring species richness and turnover by statistical multiresolution texture
      analysis of satellite imagery.
AB  - BACKGROUND: The quantification of species-richness and species-turnover is
      essential to effective monitoring of ecosystems. Wetland ecosystems are
      particularly in need of such monitoring due to their sensitivity to rainfall,
      water management and other external factors that affect hydrology, soil, and
      species patterns. A key challenge for environmental scientists is determining the
      linkage between natural and human stressors, and the effect of that linkage at
      the species level in space and time. We propose pixel intensity based Shannon
      entropy for estimating species-richness, and introduce a method based on
      statistical wavelet multiresolution texture analysis to quantitatively assess
      interseasonal and interannual species turnover. METHODOLOGY/PRINCIPAL FINDINGS:
      We model satellite images of regions of interest as textures. We define a texture
      in an image as a spatial domain where the variations in pixel intensity across
      the image are both stochastic and multiscale. To compare two textures
      quantitatively, we first obtain a multiresolution wavelet decomposition of each.
      Either an appropriate probability density function (pdf) model for the
      coefficients at each subband is selected, and its parameters estimated, or, a non
      parametric approach using histograms is adopted. We choose the former, where the
      wavelet coefficients of the multiresolution decomposition at each subband are
      modeled as samples from the generalized Gaussian pdf. We then obtain the joint
      pdf for the coefficients for all subbands, assuming independence across subbands;
      an approximation that simplifies the computational burden significantly without
      sacrificing the ability to statistically distinguish textures. We measure the
      difference between two textures' representative pdf's via the Kullback-Leibler
      divergence (KL). Species turnover, or [Formula: see text] diversity, is estimated
      using both this KL divergence and the difference in Shannon entropy.
      Additionally, we predict species richness, or [Formula: see text] diversity,
      based on the Shannon entropy of pixel intensity.To test our approach, we
      specifically use the green band of Landsat images for a water conservation area
      in the Florida Everglades. We validate our predictions against data of species
      occurrences for a twenty-eight years long period for both wet and dry seasons.
      Our method correctly predicts 73% of species richness. For species turnover, the
      newly proposed KL divergence prediction performance is near 100% accurate. This
      represents a significant improvement over the more conventional Shannon entropy
      difference, which provides 85% accuracy. Furthermore, we find that changes in
      soil and water patterns, as measured by fluctuations of the Shannon entropy for
      the red and blue bands respectively, are positively correlated with changes in
      vegetation. The fluctuations are smaller in the wet season when compared to the
      dry season. CONCLUSIONS/SIGNIFICANCE: Texture-based statistical multiresolution
      image analysis is a promising method for quantifying interseasonal differences
      and, consequently, the degree to which vegetation, soil, and water patterns vary.
      The proposed automated method for quantifying species richness and turnover can
      also provide analysis at higher spatial and temporal resolution than is currently
      obtainable from expensive monitoring campaigns, thus enabling more prompt, more
      cost effective inference and decision making support regarding anomalous
      variations in biodiversity. Additionally, a matrix-based visualization of the
      statistical multiresolution analysis is presented to facilitate both insight and
      quick recognition of anomalous data.

PMID- 23115630
TI  - A brain-computer interface based attention training program for treating
      attention deficit hyperactivity disorder.
AB  - Attention deficit hyperactivity disorder (ADHD) symptoms can be difficult to
      treat. We previously reported that a 20-session brain-computer interface (BCI)
      attention training programme improved ADHD symptoms. Here, we investigated a new
      more intensive BCI-based attention training game system on 20 unmedicated ADHD
      children (16 males, 4 females) with significant inattentive symptoms (combined
      and inattentive ADHD subtypes). This new system monitored attention through a
      head band with dry EEG sensors, which was used to drive a feed forward game. The
      system was calibrated for each user by measuring the EEG parameters during a
      Stroop task. Treatment consisted of an 8-week training comprising 24 sessions
      followed by 3 once-monthly booster training sessions. Following intervention,
      both parent-rated inattentive and hyperactive-impulsive symptoms on the ADHD
      Rating Scale showed significant improvement. At week 8, the mean improvement was 
      4.6 (5.9) and -4.7 (5.6) respectively for inattentive symptoms and hyperactive
      impulsive symptoms (both p<0.01). Cohen's d effect size for inattentive symptoms
      was large at 0.78 at week 8 and 0.84 at week 24 (post-boosters). Further analysis
      showed that the change in the EEG based BCI ADHD severity measure correlated with
      the change ADHD Rating Scale scores. The BCI-based attention training game system
      is a potential new treatment for ADHD. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT01344044.

PMID- 23115631
TI  - A lipidomic approach to understanding free fatty acid lipogenesis derived from
      dissolved inorganic carbon within cnidarian-dinoflagellate symbiosis.
AB  - The cnidarian-dinoflagellate symbiosis is arguably one of the most important
      within the marine environment in that it is integral to the formation of coral
      reefs. However, the regulatory processes that perpetuate this symbiosis remain
      unresolved. It is essential to understand these processes, if we are to elucidate
      the mechanisms that support growth and resource accumulation by coral host, and
      conversely, recently observed reduction and/or mortality of corals in response to
      rapid environmental change. This study specifically focused on one area of
      metabolic activity within the symbiosis, that of free fatty acid synthesis within
      both the dinoflagellate symbionts and cnidarian host. The main model system used
      was Aiptasia pulchella and Symbiodinium sp. in combination with aposymbiotic A.
      pulchella, the symbiotic coral Acropora millepora system and dinoflagellate
      culture. Fatty acids (FAs) were selected because of their multiple essential
      roles inclusive of energy storage (resource accumulation), membrane structure
      fluidity and cell signaling. The study addressed free FA lipogenesis by using a
      new method of enriched stable isotopic ((13)C) incorporation from dissolved
      inorganic carbon (DI(13)C) combined with HPLC-MS. FAs derived from DI(13)C
      aligned with a mixture of known lipogenesis pathways with the addition of some
      unusual FAs. After 120 hr, (13)C-enriched FA synthesis rates were attributed to
      only a complex integration of both n-3 and n-6 lipogenesis pathways within the
      dinoflagellate symbionts. Furthermore, there was no detectible evidence of
      symbiont derived enriched isotope fatty acids, catabolized (13)C derivatives or
      DI(13)C being directly utilized, in host late n-6 pathway long-chain FA
      lipogenesis. These findings do not align with a popular mutualistic translocation
      model with respect to the use of translocated symbiont photoassimilates in host
      long-chain FA lipogenesis, which has important connotations for linking nutrient
      sources with metabolite production and the dynamic regulation of this symbiosis.

PMID- 23115632
TI  - Chemical discrimination and aggressiveness via cuticular hydrocarbons in a
      supercolony-forming ant, Formica yessensis.
AB  - BACKGROUND: Territorial boundaries between conspecific social insect colonies are
      maintained through nestmate recognition systems. However, in supercolony-forming
      ants, which have developed an extraordinary social organization style known as
      unicoloniality, a single supercolony extends across large geographic distance.
      The underlying mechanism is considered to involve less frequent occurrence of
      intraspecific aggressive behaviors, while maintaining interspecific competition.
      Thus, we examined whether the supercolony-forming species, Formica yessensis has
      a nestmate recognition system similar to that of the multicolonial species,
      Camponotus japonicus with respect to the cuticular hydrocarbon-sensitive
      sensillum (CHC sensillum), which responds only to non-nestmate CHCs. We further
      investigated whether the sensory system reflects on the apparent reduced
      aggression between non-nestmates typical to unicolonial species.
      METHODOLOGY/PRINCIPAL FINDINGS: F. yessensis constructs supercolonies comprising
      numerous nests and constitutes the largest supercolonies in Japan. We compared
      the within-colony or between-colonies' (1) similarity in CHC profiles, the
      nestmate recognition cues, (2) levels of the CHC sensillar response, (3) levels
      of aggression between workers, as correlated with geographic distances between
      nests, and (4) their genetic relatedness. Workers from nests within the
      supercolony revealed a greater similarity of CHC profiles compared to workers
      from colonies outside it. Total response of the active CHC sensilla stimulated
      with conspecific alien CHCs did not increase as much as in case of C. japonicus,
      suggesting that discrimination of conspecific workers at the peripheral system is
      limited. It was particularly limited among workers within a supercolony, but was
      fully expressed for allospecific workers. CONCLUSIONS/SIGNIFICANCE: We
      demonstrate that chemical discrimination between nestmates and non-nestmates in
      F. yessensis was not clear cut, probably because this species has only subtle
      intraspecific differences in the CHC pattern that typify within a supercolony.
      Such an incomplete chemical discrimination via the CHC sensilla is thus an
      important factor contributing to decreased occurrence of intraspecific aggressive
      behavior especially within a supercolony.

PMID- 23115633
TI  - Outcomes of multidrug-resistant tuberculosis treatment with early initiation of
      antiretroviral therapy for HIV co-infected patients in Lesotho.
AB  - BACKGROUND: Although the importance of concurrent treatment for multidrug
      resistant tuberculosis (MDR-TB) and HIV co-infection has been increasingly
      recognized, there have been few studies reporting outcomes of MDR-TB and HIV co
      treatment. We report final outcomes of comprehensive, integrated MDR-TB and HIV
      treatment in Lesotho and examine factors associated with death or treatment
      failure. METHODS: We reviewed clinical charts of all adult patients who initiated
      MDR-TB treatment in Lesotho between January 2008 and September 2009. We
      calculated hazard ratios (HR) and used multivariable Cox proportional hazards
      regression to identify predictors of poor outcomes. RESULTS: Of 134 confirmed MDR
      TB patients, 83 (62%) were cured or completed treatment, 46 (34%) died, 3 (2%)
      transferred, 1 (1%) defaulted, and 1 (1%) failed treatment. Treatment outcomes
      did not differ significantly by HIV status. Among the 94 (70%) patients with HIV
      co-infection, 53% were already on antiretroviral therapy (ART) before MDR-TB
      treatment initiation, and 43% started ART a median of 16 days after the start of
      the MDR-TB regimen. Among HIV co-infected patients who died, those who had not
      started ART before MDR-TB treatment had a shorter median time to death (80 days
      vs. 138 days, p=0.065). In multivariable analysis, predictors of increased hazard
      of failure or death were low and severely low body mass index (HR 2.75, 95%
      confidence interval [CI] 1.27-5.93; HR 5.50, 95% CI 2.38-12.69), and a history of
      working in South Africa (HR 2.37, 95% CI 1.24-4.52). CONCLUSIONS: Favorable
      outcomes can be achieved in co-infected patients using a community-based
      treatment model when both MDR-TB and HIV disease are treated concurrently and
      treatment is initiated promptly.

PMID- 23115634
TI  - CNTNAP2 and language processing in healthy individuals as measured with ERPs.
AB  - The genetic FOXP2-CNTNAP2 pathway has been shown to be involved in the language
      capacity. We investigated whether a common variant of CNTNAP2 (rs7794745) is
      relevant for syntactic and semantic processing in the general population by using
      a visual sentence processing paradigm while recording ERPs in 49 healthy adults.
      While both AA homozygotes and T-carriers showed a standard N400 effect to
      semantic anomalies, the response to subject-verb agreement violations differed
      across genotype groups. T-carriers displayed an anterior negativity preceding the
      P600 effect, whereas for the AA group only a P600 effect was observed. These
      results provide another piece of evidence that the neuronal architecture of the
      human faculty of language is shaped differently by effects that are genetically
      determined.

PMID- 23115635
TI  - Regulation of epidermal growth factor receptor signaling and erlotinib
      sensitivity in head and neck cancer cells by miR-7.
AB  - Elevated expression and activity of the epidermal growth factor receptor
      (EGFR)/protein kinase B (Akt) signaling pathway is associated with development,
      progression and treatment resistance of head and neck cancer (HNC). Several
      studies have demonstrated that microRNA-7 (miR-7) regulates EGFR expression and
      Akt activity in a range of cancer cell types via its specific interaction with
      the EGFR mRNA 3'-untranslated region (3'-UTR). In the present study, we found
      that miR-7 regulated EGFR expression and Akt activity in HNC cell lines, and that
      this was associated with reduced growth in vitro and in vivo of cells (HN5) that
      were sensitive to the EGFR tyrosine kinase inhibitor (TKI) erlotinib (Tarceva).
      miR-7 acted synergistically with erlotinib to inhibit growth of erlotinib
      resistant FaDu cells, an effect associated with increased inhibition of Akt
      activity. Microarray analysis of HN5 and FaDu cell lines transfected with miR-7
      identified a common set of downregulated miR-7 target genes, providing insight
      into the tumor suppressor function of miR-7. Furthermore, we identified several
      target miR-7 mRNAs with a putative role in the sensitization of FaDu cells to
      erlotinib. Together, these data support the coordinate regulation of Akt
      signaling by miR-7 in HNC cells and suggest the therapeutic potential of miR-7
      alone or in combination with EGFR TKIs in this disease.

PMID- 23115636
TI  - In vitro modeling of paraxial mesodermal progenitors derived from induced
      pluripotent stem cells.
AB  - Induced pluripotent stem (iPS) cells are generated from adult somatic cells by
      transduction of defined factors. Given their unlimited proliferation and
      differentiation potential, iPS cells represent promising sources for cell therapy
      and tools for research and drug discovery. However, systems for the directional
      differentiation of iPS cells toward paraxial mesodermal lineages have not been
      reported. In the present study, we established a protocol for the differentiation
      of mouse iPS cells into paraxial mesodermal lineages in serum-free culture. The
      protocol was dependent on Activin signaling in addition to BMP and Wnt signaling
      which were previously shown to be effective for mouse ES cell differentiation.
      Independently of the cell origin, the number of transgenes, or the type of
      vectors used to generate iPS cells, the use of serum-free monolayer culture
      stimulated with a combination of BMP4, Activin A, and LiCl enabled preferential
      promotion of mouse iPS cells to a PDGFR-alpha(+)/Flk-1(-) population, which
      represents a paraxial mesodermal lineage. The mouse iPS cell-derived paraxial
      mesodermal cells exhibited differentiation potential into osteogenic,
      chondrogenic, and myogenic cells both in vitro and in vivo and contributed to
      muscle regeneration. Moreover, purification of the PDGFR-alpha(+)/KDR(-)
      population after differentiation allowed enrichment of human iPS cell populations
      with paraxial mesodermal characteristics. The resultant PDGFR-alpha(+)/KDR(-)
      population derived from human iPS cells specifically exhibited osteogenic,
      chondrogenic, and myogenic differentiation potential in vitro, implying
      generation of paraxial mesodermal progenitors similar to mouse iPS cell-derived
      progenitors. These findings highlight the potential of protocols based on the
      serum-free, stepwise induction and purification of paraxial mesodermal cell
      lineages for use in stem cell therapies to treat diseased bone, cartilage, and
      muscle.

PMID- 23115637
TI  - Deletion of the gabra2 gene results in hypersensitivity to the acute effects of
      ethanol but does not alter ethanol self administration.
AB  - Human genetic studies have suggested that polymorphisms of the GABRA2 gene
      encoding the GABA(A) alpha2-subunit are associated with ethanol dependence.
      Variations in this gene also convey sensitivity to the subjective effects of
      ethanol, indicating a role in mediating ethanol-related behaviours. We therefore
      investigated the consequences of deleting the alpha2-subunit on the ataxic and
      rewarding properties of ethanol in mice. Ataxic and sedative effects of ethanol
      were explored in GABA(A) alpha2-subunit wildtype (WT) and knockout (KO) mice
      using a Rotarod apparatus, wire hang and the duration of loss of righting reflex.
      Following training, KO mice showed shorter latencies to fall than WT littermates
      under ethanol (2 g/kg i.p.) in both Rotarod and wire hang tests. After
      administration of ethanol (3.5 g/kg i.p.), KO mice took longer to regain the
      righting reflex than WT mice. To ensure the acute effects are not due to the
      gabra2 deletion affecting pharmacokinetics, blood ethanol concentrations were
      measured at 20 minute intervals after acute administration (2 g/kg i.p.), and did
      not differ between genotypes. To investigate ethanol's rewarding properties, WT
      and KO mice were trained to lever press to receive increasing concentrations of
      ethanol on an FR4 schedule of reinforcement. Both WT and KO mice self
      administered ethanol at similar rates, with no differences in the numbers of
      reinforcers earned. These data indicate a protective role for alpha2-subunits,
      against the acute sedative and ataxic effects of ethanol. However, no change was
      observed in ethanol self administration, suggesting the rewarding effects of
      ethanol remain unchanged.

PMID- 23115638
TI  - Distinct contributions of Orai1 and TRPC1 to agonist-induced [Ca(2+)](i) signals
      determine specificity of Ca(2+)-dependent gene expression.
AB  - Regulation of critical cellular functions, including Ca(2+)-dependent gene
      expression, is determined by the temporal and spatial aspects of agonist-induced
      Ca(2+) signals. Stimulation of cells with physiological concentrations of
      agonists trigger increases [Ca(2+)](i) due to intracellular Ca(2+) release and
      Ca(2+) influx. While Orai1-STIM1 channels account for agonist-stimulated
      [Ca(2+)](i) increase as well as activation of NFAT in cells such as lymphocytes,
      RBL and mast cells, both Orai1-STIM1 and TRPC1-STIM1 channels contribute to
      [Ca(2+)](i) increases in human submandibular gland (HSG) cells. However, only
      Orai1-mediated Ca(2+) entry regulates the activation of NFAT in HSG cells. Since
      both TRPC1 and Orai1 are activated following internal Ca(2+) store depletion in
      these cells, it is not clear how the cells decode individual Ca(2+) signals
      generated by the two channels for the regulation of specific cellular functions.
      Here we have examined the contributions of Orai1 and TRPC1 to carbachol (CCh)
      induced [Ca(2+)](i) signals and activation of NFAT in single cells. We report
      that Orai1-mediated Ca(2+) entry generates [Ca(2+)](i) oscillations at different
      [CCh], ranging from very low to high. In contrast, TRPC1-mediated Ca(2+) entry
      generates sustained [Ca(2+)](i) elevation at high [CCh] and contributes to
      frequency of [Ca(2+)](i) oscillations at lower [agonist]. More importantly, the
      two channels are coupled to activation of distinct Ca(2+) dependent gene
      expression pathways, consistent with the different patterns of [Ca(2+)](i)
      signals mediated by them. Nuclear translocation of NFAT and NFAT-dependent gene
      expression display "all-or-none" activation that is exclusively driven by local
      [Ca(2+)](i) generated by Orai1, independent of global [Ca(2+)](i) changes or
      TRPC1-mediated Ca(2+) entry. In contrast, Ca(2+) entry via TRPC1 primarily
      regulates NFkappaB-mediated gene expression. Together, these findings reveal that
      Orai1 and TRPC1 mediate distinct local and global Ca(2+) signals following
      agonist stimulation of cells, which determine the functional specificity of the
      channels in activating different Ca(2+)-dependent gene expression pathways.

PMID- 23115639
TI  - Evidence for the involvement of p38 MAPK activation in barnacle larval
      settlement.
AB  - The barnacle Balanus ( = Amphibalanus) amphitrite is a major marine fouling
      animal. Understanding the molecular mechanism of larval settlement in this
      species is critical for anti-fouling research. In this study, we cloned one
      isoform of p38 MAPK (Bar-p38 MAPK) from this species, which shares the
      significant characteristic of containing a TGY motif with other species such as
      yeast, Drosophila and humans. The activation of p38 MAPK was detected by an
      antibody that recognizes the conserved dual phosphorylation sites of TGY. The
      results showed that phospho-p38 MAPK (pp38 MAPK) was more highly expressed at the
      cyprid stage, particularly in aged cyprids, in comparison to other stages,
      including the nauplius and juvenile stages. Immunostaining showed that Bar-p38
      MAPK and pp38 MAPK were mainly located at the cyprid antennules, and especially
      the third and fourth segments, which are responsible for substratum exploration
      during settlement. The expression and localization patterns of Bar-p38 MAPK
      suggest its involvement in larval settlement. This postulation was also supported
      by the larval settlement bioassay with the p38 MAPK inhibitor SB203580.
      Behavioral analysis by live imaging revealed that the larvae were still capable
      of exploring the surface of the substratum after SB203580 treatment. This shows
      that the effect of p38 MAPK on larval settlement might be by regulating the
      secretion of permanent proteinaceous substances. Furthermore, the level of pp38
      MAPK dramatically decreased after full settlement, suggesting that Bar-p38 MAPK
      maybe plays a role in larval settlement rather than metamorphosis. Finally, we
      found that Bar-p38 MAPK was highly activated when larvae confronted extracts of
      adult barnacle containing settlement cues, whereas larvae pre-treated with
      SB203580 failed to respond to the crude adult extracts.

PMID- 23115640
TI  - Inflammation disrupts the LDL receptor pathway and accelerates the progression of
      vascular calcification in ESRD patients.
AB  - BACKGROUND: Chronic inflammation plays a crucial role in the progression of
      vascular calcification (VC). This study was designed to investigate whether the
      low-density lipoprotein receptor (LDLr) pathway is involved in the progression of
      VC in patients with end-stage renal disease (ESRD) during inflammation. METHODS
      AND RESULTS: Twenty-eight ESRD patients were divided into control and inflamed
      groups according to plasma C-reactive protein (CRP) level. Surgically removed
      tissues from the radial arteries of patients receiving arteriovenostomy were used
      in the experiments. The expression of tumour necrosis factor-alpha (TNF-alpha)
      and monocyte chemotactic protein-1 (MCP-1) of the radial artery were increased in
      the inflamed group. Hematoxylin-eosin and alizarin red S staining revealed
      parallel increases in foam cell formation and calcium deposit formation in
      continuous cross-sections of radial arteries in the inflamed group compared to
      the control, which were closely correlated with increased LDLr, sterol regulatory
      element binding protein-2 (SREBP-2), bone morphogenetic proteins-2 (BMP-2), and
      collagen I protein expression, as shown by immunohistochemical and
      immunofluorescent staining. Confocal microscopy confirmed that inflammation
      enhanced the translocation of the SREBP cleavage-activating protein (SCAP)/SREBP
      2 complex from the endoplasmic reticulum to the Golgi, thereby activating LDLr
      gene transcription. Inflammation increased alkaline phosphatase protein
      expression and reduced alpha-smooth muscle actin protein expression, contributing
      to the conversion of the vascular smooth muscle cells in calcified vessels from
      the fibroblastic to the osteogenic phenotype; osteogenic cells are the main
      cellular components involved in VC. Further analysis showed that the inflammation
      induced disruption of the LDLr pathway was significantly associated with enhanced
      BMP-2 and collagen I expression. CONCLUSIONS: Inflammation accelerated the
      progression of VC in ESRD patients by disrupting the LDLr pathway, which may
      represent a novel mechanism involved in the progression of both VC and
      atherosclerosis.

PMID- 23115641
TI  - Surface expression and subunit specific control of steady protein levels by the
      Kv7.2 helix A-B linker.
AB  - Kv7.2 and Kv7.3 are the main components of the neuronal voltage-dependent M
      current, which is a subthreshold potassium conductance that exerts an important
      control on neuronal excitability. Despite their predominantly intracellular
      distribution, these channels must reach the plasma membrane in order to control
      neuronal activity. Thus, we analyzed the amino acid sequence of Kv7.2 to identify
      intrinsic signals that may control its surface expression. Removal of the
      interlinker connecting helix A and helix B of the intracellular C-terminus
      produces a large increase in the number of functional channels at the plasma
      membrane. Moreover, elimination of this linker increased the steady-state amount
      of protein, which was not associated with a decrease of protein degradation. The
      magnitude of this increase was inversely correlated with the number of helix A -
      helix B linkers present in the tetrameric channel assemblies. In contrast to the
      remarkable effect on the amount of Kv7.2 protein, removal of the Kv7.2 linker had
      no detectable impact on the steady-state levels of Kv7.3 protein.

PMID- 23115642
TI  - Phylogeography of Quercus variabilis based on chloroplast DNA sequence in East
      Asia: multiple glacial refugia and Mainland-migrated island populations.
AB  - The biogeographical relationships between far-separated populations, in
      particular, those in the mainland and islands, remain unclear for widespread
      species in eastern Asia where the current distribution of plants was greatly
      influenced by the Quaternary climate. Deciduous Oriental oak (Quercus variabilis)
      is one of the most widely distributed species in eastern Asia. In this study,
      leaf material of 528 Q. variabilis trees from 50 populations across the whole
      distribution (Mainland China, Korea Peninsular as well as Japan, Zhoushan and
      Taiwan Islands) was collected, and three cpDNA intergenic spacer fragments were
      sequenced using universal primers. A total of 26 haplotypes were detected, and it
      showed a weak phylogeographical structure in eastern Asia populations at species
      level, however, in the central-eastern region of Mainland China, the populations
      had more haplotypes than those in other regions, with a significant
      phylogeographical structure (N(ST= )0.751> G(ST= )0.690, P<0.05). Q. variabilis
      displayed high interpopulation and low intrapopulation genetic diversity across
      the distribution range. Both unimodal mismatch distribution and significant
      negative Fu's F(S) indicated a demographic expansion of Q. variabilis populations
      in East Asia. A fossil calibrated phylogenetic tree showed a rapid speciation
      during Pleistocene, with a population augment occurred in Middle Pleistocene.
      Both diversity patterns and ecological niche modelling indicated there could be
      multiple glacial refugia and possible bottleneck or founder effects occurred in
      the southern Japan. We dated major spatial expansion of Q. variabilis population
      in eastern Asia to the last glacial cycle(s), a period with sea-level
      fluctuations and land bridges in East China Sea as possible dispersal corridors.
      This study showed that geographical heterogeneity combined with climate and sea
      level changes have shaped the genetic structure of this wide-ranging tree species
      in East Asia.

PMID- 23115643
TI  - Influenza infects lung microvascular endothelium leading to microvascular leak:
      role of apoptosis and claudin-5.
AB  - Severe influenza infections are complicated by acute lung injury, a syndrome of
      pulmonary microvascular leak. The pathogenesis of this complication is unclear.
      We hypothesized that human influenza could directly infect the lung microvascular
      endothelium, leading to loss of endothelial barrier function. We infected human
      lung microvascular endothelium with both clinical and laboratory strains of human
      influenza. Permeability of endothelial monolayers was assessed by
      spectrofluorimetry and by measurement of the transendothelial electrical
      resistance. We determined the molecular mechanisms of flu-induced endothelial
      permeability and developed a mouse model of severe influenza. We found that both
      clinical and laboratory strains of human influenza can infect and replicate in
      human pulmonary microvascular endothelium, leading to a marked increase in
      permeability. This was caused by apoptosis of the lung endothelium, since
      inhibition of caspases greatly attenuated influenza-induced endothelial leak.
      Remarkably, replication-deficient virus also caused a significant degree of
      endothelial permeability, despite displaying no cytotoxic effects to the
      endothelium. Instead, replication-deficient virus induced degradation of the
      tight junction protein claudin-5; the adherens junction protein VE-cadherin and
      the actin cytoskeleton were unaffected. Over-expression of claudin-5 was
      sufficient to prevent replication-deficient virus-induced permeability. The
      barrier-protective agent formoterol was able to markedly attenuate flu-induced
      leak in association with dose-dependent induction of claudin-5. Finally, mice
      infected with human influenza developed pulmonary edema that was abrogated by
      parenteral treatment with formoterol. Thus, we describe two distinct mechanisms
      by which human influenza can induce pulmonary microvascular leak. Our findings
      have implications for the pathogenesis and treatment of acute lung injury from
      severe influenza.

PMID- 23115644
TI  - Identifying factors to improve oral cancer screening uptake: a qualitative study.
AB  - AIMS: To engage with high risk groups to identify knowledge and awareness of oral
      cancer signs and symptoms and the factors likely to contribute to improved
      screening uptake. METHODS: Focus group discussions were undertaken with 18 males;
      40+ years of age; smokers and/or drinkers (15+ cigarettes per day and/or 15+
      units of alcohol per week), irregular dental attenders living in economically
      deprived areas of Teesside. RESULTS: There was a striking reported lack of
      knowledge and awareness of oral cancer and its signs and symptoms among the
      participants. When oral/mouth cancer leaflets produced by Cancer Research UK were
      presented to the participants, they claimed that they would seek help on noticing
      such a condition. There was a preference to seek help from their general
      practitioner rather than their dentist due to perceptions that a dentist is
      'inaccessible' on a physical and psychological level, costly, a 'tooth
      specialist' not a 'mouth specialist', and also not able to prescribe medication
      and make referrals to specialists. Interestingly, none of the 18 participants who
      were offered a free oral cancer examination at a dental practice took up this
      offer. CONCLUSIONS: The uptake of oral cancer screening may be improved by
      increasing knowledge of the existence and signs and symptoms of oral cancer.
      Other factors that may increase uptake are increased awareness of the role of
      dentists in diagnosing oral cancer, promotion of oral cancer screening by health
      professionals during routine health checks, and the use of a "health" screening
      setting as opposed to a "dental" setting for such checks.

PMID- 23115645
TI  - Inbreeding depression under drought stress in the rare endemic Echium wildpretii
      (Boraginaceae) on Tenerife, Canary islands.
AB  - How climate-change induced environmental stress may alter the effects of
      inbreeding in patchy populations of rare species is poorly understood. We
      investigated the fitness of progeny from experimental self- and cross
      pollinations in eight populations of different size of Echium wildpretii, a rare
      endemic plant of the arid subalpine zone of the Canarian island of Tenerife. As
      control treatments we used open pollination and autonomous selfing. The seed set
      of open-pollinated flowers was 55% higher than that of autonomously selfed
      flowers, showing the importance of animal pollination for reproductive success.
      The seed set, seed mass and germination rate of seedlings of hand-selfed flowers
      was similar to that of hand-crossed flowers, indicating weak inbreeding
      depression (seed set -4.4%, seed mass -4.1%, germination -7.3%). Similarly, under
      normal watering there were no significant effects of inbreeding on seedling
      survival (-3.0%). However, under low watering of seedlings inbreeding depression
      was high (survival -50.2%). Seed set of open- and hand-outcrossed-pollinated
      flowers was higher in large than in small populations, possibly due to more
      frequent biparental inbreeding in the latter. However, later measures of progeny
      fitness were not significantly influenced by population size. We predict that
      increasing drought duration and frequency due to climate change and reductions of
      population sizes may increase inbreeding depression in this charismatic plant
      species and thus threaten its future survival in the longer term.

PMID- 23115646
TI  - Large impact of low concentration oxidized LDL on angiogenic potential of human
      endothelial cells: a microarray study.
AB  - Oxidized LDL (ox-LDL) is a key factor in atherogenesis. It is taken up by
      endothelial cells primarily by ox-LDL receptor-1 (LOX-1). To elucidate
      transcriptional responses, we performed microarray analysis on human coronary
      artery endothelial cells (HCAECs) exposed to small physiologic concentration of
      ox-LDL- 5 ug/ml for 2 and 12 hours. At 12 hours, cultures treated with ox-LDL
      exhibited broad shifts in transcriptional activity involving almost 1500 genes
      (>1.5 fold difference, p<0.05). Resulting transcriptome was enriched for genes
      associated with cell adhesion (p<0.002), angiogenesis (p<0.0002) and migration
      (p<0.006). Quantitative PCR analysis revealed that LOX-1 expression in HCAECs is
      at least an order of magnitude greater than the expression of other major ox-LDL
      specific receptors CD36 and MSR1. In keeping with the data on LOX-1 expression,
      pre-treatment of HCAECs with LOX-1 neutralizing antibody resulted in across-the
      board inhibition of cellular response to ox-LDL. Ox-LDL upregulated a number of
      pro-angiogenic genes including multiple receptors, ligands and transcription
      factors and altered the expression of a number of genes implicated in both
      stimulation and inhibition of apoptosis. From a functional standpoint,
      physiologic concentrations of ox-LDL stimulated tube formation and inhibited
      susceptibility to apoptosis in HCAECs. In addition, ox-LDL exposure resulted in
      upregulation of miR-1974, miR-1978 and miR-21 accompanied with significant over
      presentation of their target genes in the downregulated portion of ox-LDL
      transcriptome. Our observations indicate that ox-LDL at physiologic
      concentrations induces broad transcriptional responses which are mediated by LOX
      1, and are, in part, shaped by ox-LDL-dependent miRNAs. We also suggest that
      angiogenic effects of ox-LDL are partially based on upregulation of several
      receptors that render cells hypersensitive to angiogenic stimuli.

PMID- 23115647
TI  - The kinematics of swimming and relocation jumps in copepod nauplii.
AB  - Copepod nauplii move in a world dominated by viscosity. Their swimming-by-jumping
      propulsion mode, with alternating power and recovery strokes of three pairs of
      cephalic appendages, is fundamentally different from the way other microplankters
      move. Protozoans move using cilia or flagella, and copepodites are equipped with
      highly specialized swimming legs. In some species the nauplius may also propel
      itself more slowly through the water by beating and rotating the appendages in a
      different, more complex pattern. We use high-speed video to describe jumping and
      swimming in nauplii of three species of pelagic copepods: Temora longicornis,
      Oithona davisae and Acartia tonsa. The kinematics of jumping is similar between
      the three species. Jumps result in a very erratic translation with no phase of
      passive coasting and the nauplii move backwards during recovery strokes. This is
      due to poorly synchronized recovery strokes and a low beat frequency relative to
      the coasting time scale. For the same reason, the propulsion efficiency of the
      nauplii is low. Given the universality of the nauplius body plan, it is
      surprising that they seem to be inefficient when jumping, which is different from
      the very efficient larger copepodites. A slow-swimming mode is only displayed by
      T. longicornis. In this mode, beating of the appendages results in the creation
      of a strong feeding current that is about 10 times faster than the average
      translation speed of the nauplius. The nauplius is thus essentially hovering when
      feeding, which results in a higher feeding efficiency than that of a nauplius
      cruising through the water.

PMID- 23115648
TI  - Visualization of endothelial actin cytoskeleton in the mouse retina.
AB  - Angiogenesis requires coordinated changes in cell shape of endothelial cells
      (ECs), orchestrated by the actin cytoskeleton. The mechanisms that regulate this
      rearrangement in vivo are poorly understood - largely because of the difficulty
      to visualize filamentous actin (F-actin) structures with sufficient resolution.
      Here, we use transgenic mice expressing Lifeact-EGFP to visualize F-actin in ECs.
      We show that in the retina, Lifeact-EGFP expression is largely restricted to ECs
      allowing detailed visualization of F-actin in ECs in situ. Lifeact-EGFP labels
      actin associated with cell-cell junctions, apical and basal membranes and
      highlights actin-based structures such as filopodia and stress fiber-like
      cytoplasmic bundles. We also show that in the skin and the skeletal muscle,
      Lifeact-EGFP is highly expressed in vascular mural cells (vMCs), enabling vMC
      imaging. In summary, our results indicate that the Lifeact-EGFP transgenic mouse
      in combination with the postnatal retinal angiogenic model constitutes an
      excellent system for vascular cell biology research. Our approach is ideally
      suited to address structural and mechanistic details of angiogenic processes,
      such as endothelial tip cell migration and fusion, EC polarization or lumen
      formation.

PMID- 23115649
TI  - Regulation of insulin and leptin signaling by muscle suppressor of cytokine
      signaling 3 (SOCS3).
AB  - Skeletal muscle resistance to the key metabolic hormones, leptin and insulin, is
      an early defect in obesity. Suppressor of cytokine signaling 3 (SOCS3) is a major
      negative regulator of both leptin and insulin signaling, thereby implicating
      SOCS3 in the pathogenesis of obesity and associated metabolic abnormalities.
      Here, we demonstrate that SOCS3 mRNA expression is increased in murine skeletal
      muscle in the setting of diet-induced and genetic obesity, inflammation, and
      hyperlipidemia. To further evaluate the contribution of muscle SOCS3 to leptin
      and insulin resistance in obesity, we generated transgenic mice with muscle
      specific overexpression of SOCS3 (MCK/SOCS3 mice). Despite similar body weight,
      MCK/SOCS3 mice develop impaired systemic and muscle-specific glucose homeostasis
      and insulin action based on glucose and insulin tolerance tests, hyperinsulinemic
      euglycemic clamps, and insulin signaling studies. With regards to leptin action,
      MCK/SOCS3 mice exhibit suppressed basal and leptin-stimulated activity and
      phosphorylation of alpha2 AMP-activated protein kinase (alpha2AMPK) and its
      downstream target, acetyl-CoA carboxylase (ACC). Muscle SOCS3 overexpression also
      suppresses leptin-regulated genes involved in fatty acid oxidation and
      mitochondrial function. These studies demonstrate that SOC3 within skeletal
      muscle is a critical regulator of leptin and insulin action and that increased
      SOCS may mediate insulin and leptin resistance in obesity.

PMID- 23115650
TI  - A cost effectiveness and capacity analysis for the introduction of universal
      rotavirus vaccination in Kenya: comparison between Rotarix and RotaTeq vaccines.
AB  - BACKGROUND: Diarrhoea is an important cause of death in the developing world, and
      rotavirus is the single most important cause of diarrhoea associated mortality.
      Two vaccines (Rotarix and RotaTeq) are available to prevent rotavirus disease.
      This analysis was undertaken to aid the decision in Kenya as to which vaccine to
      choose when introducing rotavirus vaccination. METHODS: Cost-effectiveness
      modelling, using national and sentinel surveillance data, and an impact
      assessment on the cold chain. RESULTS: The median estimated incidence of
      rotavirus disease in Kenya was 3015 outpatient visits, 279 hospitalisations and
      65 deaths per 100,000 children under five years of age per year. Cumulated over
      the first five years of life vaccination was predicted to prevent 34% of the
      outpatient visits, 31% of the hospitalizations and 42% of the deaths. The
      estimated prevented costs accumulated over five years totalled US$1,782,761
      (direct and indirect costs) with an associated 48,585 DALYs. From a societal
      perspective Rotarix had a cost-effectiveness ratio of US$142 per DALY (US$5 for
      the full course of two doses) and RotaTeq US$288 per DALY ($10.5 for the full
      course of three doses). RotaTeq will have a bigger impact on the cold chain
      compared to Rotarix. CONCLUSION: Vaccination against rotavirus disease is cost
      effective for Kenya irrespective of the vaccine. Of the two vaccines Rotarix was
      the preferred choice due to a better cost-effectiveness ratio, the presence of a
      vaccine vial monitor, the requirement of fewer doses and less storage space, and
      proven thermo-stability.

PMID- 23115651
TI  - The effects of ecstasy (MDMA) on brain serotonin transporters are dependent on
      age-of-first exposure in recreational users and animals.
AB  - RATIONALE AND OBJECTIVE: Little is known on the effects of ecstasy (MDMA, a
      potent 5-HT-releaser and neurotoxin) exposure on brain development in teenagers.
      The objective of this study was to investigate whether in humans, like previous
      observations made in animals, the effects of MDMA on the 5-HT system are
      dependent on age-of-first exposure. METHODS: 5-HT transporter (SERT) densities in
      the frontal cortex and midbrain were assessed with [(123)I]beta-CIT single photon
      emission computed tomography in 33 users of ecstasy. Subjects were stratified for
      early-exposed users (age-at-first exposure 14-18 years; developing brain), and
      late-exposed users (age-at-first exposure 18-36 years; mature brain). In
      parallel, we investigated the effects of age experimentally with MDMA in early
      exposed (adolescent) rats and late-exposed (adult) rats using the same
      radioligand. RESULTS: On average, five years after first exposure, we found a
      strong inverse relationship, wherein age-at-first exposure predicted 79% of the
      midbrain SERT variability in early (developing brain) exposed ecstasy users,
      whereas this was only 0.3% in late (mature brain) exposed users (p=0.007). No
      such effect was observed in the frontal cortex. In rats, a significant age-BY
      treatment effect (p<0.01) was observed as well, however only in the frontal
      cortex. CONCLUSIONS: These age-related effects most likely reflect differences in
      the maturational stage of the 5-HT projection fields at age-at-first exposure and
      enhanced outgrowth of the 5-HT system due to 5-HT's neurotrophic effects.
      Ultimately, our findings stress the need for more knowledge on the effects of
      pharmacotherapies that alter brain 5-HT levels in the pediatric population.

PMID- 23115652
TI  - Bloodstream infection among children presenting to a general hospital outpatient
      clinic in urban Nepal.
AB  - BACKGROUND: There are limited data on the etiology and characteristics of
      bloodstream infections in children presenting in hospital outpatient settings in
      South Asia. Previous studies in Nepal have highlighted the importance of murine
      typhus as a cause of febrile illness in adults and enteric fever as a leading
      bacterial cause of fever among children admitted to hospital. METHODS: We
      prospectively studied a total of 1084 febrile children aged between 2 months and
      14 years presenting to a general hospital outpatient department in Kathmandu
      Valley, Nepal, over two study periods (summer and winter). Blood from all
      patients was tested by conventional culture and by real-time PCR for Rickettsia
      typhi. RESULTS: Putative etiological agents for fever were identified in 164
      (15%) patients. Salmonella enterica serovar Typhi (S. Typhi) was identified in
      107 (10%), S. enterica serovar Paratyphi A (S. Paratyphi) in 30 (3%),
      Streptococcus pneumoniae in 6 (0.6%), S. enterica serovar Typhimurium in 2
      (0.2%), Haemophilus influenzae type b in 1 (0.1%), and Escherichia coli in 1
      (0.1%) patient. S. Typhi was the most common organism isolated from blood during
      both summer and winter. Twenty-two (2%) patients were PCR positive for R. typhi.
      No significant demographic, clinical and laboratory features distinguished
      culture positive enteric fever and murine typhus. CONCLUSIONS: Salmonella
      infections are the leading cause of bloodstream infection among pediatric
      outpatients with fever in Kathmandu Valley. Extension of immunization programs
      against invasive bacterial disease to include the agents of enteric fever and
      pneumococcus could improve the health of children in Nepal.

PMID- 23115653
TI  - Soluble axoplasm enriched from injured CNS axons reveals the early modulation of
      the actin cytoskeleton.
AB  - Axon injury and degeneration is a common consequence of diverse neurological
      conditions including multiple sclerosis, traumatic brain injury and spinal cord
      injury. The molecular events underlying axon degeneration are poorly understood.
      We have developed a novel method to enrich for axoplasm from rodent optic nerve
      and characterised the early events in Wallerian degeneration using an unbiased
      proteomics screen. Our detergent-free method draws axoplasm into a dehydrated
      hydrogel of the polymer poly(2-hydroxyethyl methacrylate), which is then
      recovered using centrifugation. This technique is able to recover axonal proteins
      and significantly deplete glial contamination as confirmed by immunoblotting. We
      have used iTRAQ to compare axoplasm-enriched samples from naive vs injured optic
      nerves, which has revealed a pronounced modulation of proteins associated with
      the actin cytoskeleton. To confirm the modulation of the actin cytoskeleton in
      injured axons we focused on the RhoA pathway. Western blotting revealed an
      augmentation of RhoA and phosphorylated cofilin in axoplasm-enriched samples from
      injured optic nerve. To investigate the localisation of these components of the
      RhoA pathway in injured axons we transected axons of primary hippocampal neurons
      in vitro. We observed an early modulation of filamentous actin with a concomitant
      redistribution of phosphorylated cofilin in injured axons. At later time-points,
      RhoA is found to accumulate in axonal swellings and also colocalises with
      filamentous actin. The actin cytoskeleton is a known sensor of cell viability
      across multiple eukaryotes, and our results suggest a similar role for the actin
      cytoskeleton following axon injury. In agreement with other reports, our data
      also highlights the role of the RhoA pathway in axon degeneration. These findings
      highlight a previously unexplored area of axon biology, which may open novel
      avenues to prevent axon degeneration. Our method for isolating CNS axoplasm also
      represents a new tool to study axon biology.

PMID- 23115654
TI  - Costs of defense and a test of the carbon-nutrient balance and growth
      differentiation balance hypotheses for two co-occurring classes of plant defense.
AB  - One of the goals of chemical ecology is to assess costs of plant defenses.
      Intraspecific trade-offs between growth and defense are traditionally viewed in
      the context of the carbon-nutrient balance hypothesis (CNBH) and the growth
      differentiation balance hypothesis (GDBH). Broadly, these hypotheses suggest that
      growth is limited by deficiencies in carbon or nitrogen while rates of
      photosynthesis remain unchanged, and the subsequent reduced growth results in the
      more abundant resource being invested in increased defense (mass-balance based
      allocation). The GDBH further predicts trade-offs in growth and defense should
      only be observed when resources are abundant. Most support for these hypotheses
      comes from work with phenolics. We examined trade-offs related to production of
      two classes of defenses, saponins (triterpenoids) and flavans (phenolics), in
      Pentaclethra macroloba (Fabaceae), an abundant tree in Costa Rican wet forests.
      We quantified physiological costs of plant defenses by measuring photosynthetic
      parameters (which are often assumed to be stable) in addition to biomass.
      Pentaclethra macroloba were grown in full sunlight or shade under three levels of
      nitrogen alone or with conspecific neighbors that could potentially alter
      nutrient availability via competition or facilitation. Biomass and photosynthesis
      were not affected by nitrogen or competition for seedlings in full sunlight, but
      they responded positively to nitrogen in shade-grown plants. The trade-off
      predicted by the GDBH between growth and metabolite production was only present
      between flavans and biomass in sun-grown plants (abundant resource conditions).
      Support was also only partial for the CNBH as flavans declined with nitrogen but
      saponins increased. This suggests saponin production should be considered in
      terms of detailed biosynthetic pathway models while phenolic production fits mass
      balance based allocation models (such as the CNBH). Contrary to expectations
      based on the two defense hypotheses, trade-offs were found between defenses and
      photosynthesis, indicating that studies of plant defenses should include direct
      measures of physiological responses.

PMID- 23115655
TI  - Salivary immunoglobulin classes in Nigerian smokers with periodontitis.
AB  - AIM: To determine the levels of salivary immunoglobulin classes in Nigerian
      smokers and non-smokers with periodontitis. METHODS: Sixty-nine individuals were
      recruited into this study after obtaining informed consent. They were subdivided
      into three groups that consisted of 20 (aged 46 +/- 11 years) cigarette smokers
      with periodontitis (S+P); 24 (40 +/- 12 years) smokers without periodontitis (S
      P); and 25 (53 +/- 11 years) non-smokers with periodontitis (NS+P). An oral and
      maxillofacial surgeon used radiographs for periodontal probing for the diagnosis
      of periodontitis. The smokers included subjects who smoked at least six
      cigarettes per day and all the periodontitis patients were newly diagnosed. About
      5 mL of unstimulated saliva was expectorated by each subject into plain sample
      bottles. Salivary immunoglobulin levels were estimated using enzyme linked
      immunosorbent assay. Student's t test was used to determine significant
      differences between the means. Values of P < 0.05 were regarded as significant.
      RESULTS: No significant differences were observed in the mean salivary levels of
      the immunoglobulin classes (IgG, IgA, IgM and IgE) when S+P was compared with S
      P. Mean salivary levels of IgA (520.0 +/- 155.1 ng/mL vs 670.0 +/- 110 ng/mL, P =
      0.000) and IgM (644.5 +/- 160.0 ng/mL vs 791.4 +/- 43.7 ng/mL, P = 0.000) were
      significantly lower in the S+P compared with NS+P group. Salivary IgA (570.4 +/-
      145.6 ng/mL vs 670.0 +/- 110 ng/mL, P = 0.008) and IgM (703.1 +/- 169.3 ng/mL vs
      791.4 +/- 43.7 ng/mL, P = 0.012) levels were significantly lower in the S-P
      compared with NS+P group. Only one (5%) periodontal patient had detectable levels
      of salivary IgE (0.20 IU/mL). Similarly, only one smoker (4.17%) had detectable
      levels of salivary IgE (0.04 IU/mL) and two non-smokers (9.52%) had detectable
      levels of IgE (0.24 IU/mL). CONCLUSION: Our study suggests that reduced salivary
      IgA and IgM levels in smokers with periodontitis could enhance increased
      susceptibility to periodontitis.

PMID- 23115656
TI  - Aneurysmal subarachnoid hemorrhage in third and fourth decades of life.
AB  - OBJECTIVE: The aim of this study was to compare clinical characteristics of
      ruptured aneurysms in young adults, of the third and fourth decades of life, and
      to compare several clinical characteristics affecting the outcome of patients.
      METHODS: We retrospectively investigated 1459 patients who underwent surgery and
      endovascular treatment for ruptured cerebral aneurysms from June 1992 to December
      2010 and compared clinical characteristics. We also reviewed pre-existing medical
      conditions and perioperative complications. RESULTS: Among 1459 patients, there
      were 21 patients (1.44%) in the third decade and 104 patients (7.13%) in the
      fourth decade of life. Within two age groups, 88 (70.4%) were male and 37 (29.6%)
      were female, a ratio of 2.37 : 1. In both groups, we observed the anterior
      cerebral artery (ACA) aneurysm with the most frequency (p=0.028). In general,
      favorable outcome was achieved in both age groups (90.5% and 81.7%,
      respectively). An initial univariate analysis showed Hunt-Hess grade, Fisher
      grade, location of aneurysm, and rebleeding significantly associated with outcome
      after aneurysm rupture. Further, multivariate analysis demonstrated that only
      Hunt-Hess grade (grade 4-5) was a risk factor for the outcome (odds ratio=9.730,
      95% confidence interval 2.069-45.756, p=0.004). CONCLUSION: The incidence of
      subarachnoid hemorrhage (SAH) was higher in the male population of the third and
      fourth decades of life. Aneurysms on the ACA were most frequently occurred in
      both age groups and the outcome of aneurysmal SAH among the third and fourth
      decades was favorable. Multivariate analysis revealed that high Hunt-Hess grade
      was a risk factor for patient's outcome.

PMID- 23115657
TI  - Angiographic features and clinical outcomes of intra-arterial nimodipine
      injection in patients with subarachnoid hemorrhage-induced vasospasm.
AB  - OBJECTIVE: The aim of this study was to determine the role of intra-arterial (IA)
      nimodipine injections for cerebral vasospasm secondary to ruptured subarachnoid
      hemorrhage (SAH) and to investigate the factors that influence vasodilation and
      clinical outcomes. METHODS: We enrolled 29 patients who underwent aneurysm
      clipping for ruptured cerebral aneurysms between 2009 and 2011, and who received
      IA nimodipine after subsequently presenting with symptomatic vasospasm. The
      degree of vasodilation shown in angiography was measured, and the correlation
      between the degree of vasodilation and both the interval from SAH to cerebral
      vasospasm and the interval from clipping to cerebral vasospasm was determined.
      The change in blood flow rate after IA injection was assessed by transcranial
      Doppler ultrasound. Multiple clinical parameters were completed before and after
      IA nimodipine injection to evaluate any improvements in clinical symptoms.
      RESULTS: For eight patients, Glasgow Coma Scale (GCS) scores increased by two or
      more points. The regression analysis demonstrated a positive correlation between
      the change in GCS scores after IA nimodipine injection and the change in blood
      vessel diameter (p=0.025). A positive correlation was also observed between the
      interval from SAH to vasospasm and the change in diameter (p=0.040); and the
      interval from clipping to vasospasm and the change in diameter (p=0.022).
      CONCLUSION: IA nimodipine injection for SAH-induced vasospasm led to significant
      vasodilation in angiography and improvement in clinical symptoms without
      significant complications. Our findings suggest that IA nimodipine injection
      should be utilized when intractable vasospasm develops despite rigorous
      conservative management.

PMID- 23115658
TI  - The quality of life of patients with good outcomes after anterior circulation
      aneurysm surgery assessed by the world health organization quality of life
      instrument-korean version.
AB  - OBJECTIVE: Even in the patients with neurologically good outcome after
      intracranial aneurysm surgery, their perception of health is an important outcome
      issue. This study aimed to investigate the quality of life (QOL) and its
      predictors of patients who had a good outcome following anterior circulation
      aneurysm surgery as using the World Health Organization Quality of Life
      instrument-Korean version. METHODS: We treated 280 patients with 290 intracranial
      aneurysms for 2 years. This questionnaire was taken and validated by 99 patients
      whose Glasgow Outcome Scale score was 4 and more and Global deterioration scale 3
      and less at 6 months after the operation, and 85 normal persons. Each domain and
      facet was compared between the two groups, and a subgroup analysis was performed
      on the QOL values and hospital expenses of the aneurysm patients according to the
      type of craniotomy, approach, bleeding of the aneurysm and brain injury. RESULTS:
      Aneurysm patients showed a lower quality of life compared with control patients
      in level of independence, psychological, environmental, and spiritual domains. In
      the environmental domain, there were significant intergroup differences according
      to the type of craniotomy and the surgical approach used on the patients
      (p<0.05). The hospital charges were also significantly different according to the
      type of craniotomy (p<0.05). CONCLUSION: Despite good neurological status,
      patients surgically treated for anterior circulation aneurysm have a low quality
      of life. The craniotomy size may affect the QOL of patients who underwent an
      anterior circulation aneurysm surgery and exhibited a good outcome.

PMID- 23115659
TI  - Y-stenting endovascular treatment for ruptured intracranial aneurysms : a single
      institution experience in Korea.
AB  - OBJECTIVE: Stent-assisted coiling on intracranial aneurysm has been considered as
      an effective technique and has made the complex aneurysms amenable to coiling. To
      achieve reconstruction of intracranial vessels with preservation of parent artery
      the use of stents has the greatest potential for assisted coiling. We report the
      results of our experiences in ruptured wide-necked intracranial aneurysms using Y
      stent coiling. METHODS: From October 2003 to October 2011, 12 patients (3 men, 9
      women; mean age, 62.6) harboring 12 complex ruptured aneurysms (3 middle cerebral
      artery, 9 basilar tip) were treated by Y-stent coiling by using self-expandable
      intracranial stents. Procedural complications, clinical outcome, and initial and
      midterm angiographic results were evaluated. The definition of broad-necked
      aneurysm is neck diameter over than 4 mm or an aneurysm with a neck diameter
      smaller than 4 mm in which the dome/neck ratio was less than 2. RESULTS: In all
      patients, the aneurysm was successfully occluded with no apparent procedure
      related complication. There was no evidence of thromboembolic complication,
      arterial dissection and spasm during procedure. Follow-up studies showed stable
      and complete occlusion of the aneurysm in all patients with no neurologic
      deficits. CONCLUSION: The present study did show that the Y-stent coiling seemed
      to facilitate endovascular treatment of ruptured wide-necked intracranial
      aneurysms. More clinical data with longer follow-up are needed to establish the
      role of Y-stent coiling in ruptured aneurysms.

PMID- 23115660
TI  - Incidence and risk factors for leptomeningeal carcinomatosis in breast cancer
      patients with parenchymal brain metastases.
AB  - OBJECTIVE: The objective of study is to evaluate the incidence of leptomeningeal
      carcinomatosis (LMC) in breast cancer patients with parenchymal brain metastases
      (PBM) and clinical risk factors for the development of LMC. METHODS: We
      retrospectively analyzed 27 patients who had undergone surgical resection (SR)
      and 156 patients with whole brain radiation therapy (WBRT) as an initial
      treatment for their PBM from breast cancer in our institution and compared the
      difference of incidence of LMC according to clinical factors. The diagnosis of
      LMC was made by cerebrospinal fluid cytology and/or magnetic resonance imaging.
      RESULTS: A total of 27 patients (14%) in the study population developed LMC at a
      median of 6.0 months (range, 1.0-50). Ten of 27 patients (37%) developed LMC
      after SR, whereas 17 of 156 (11%) patients who received WBRT were diagnosed with
      LMC after the index procedure. The incidence of LMC was significantly higher in
      the SR group compared with the WBRT group and the hazard ratio was 2.95 (95%
      confidence interval; 1.33-6.54, p<0.01). Three additional factors were identified
      in the multivariable analysis : the younger age group (<40 years old), the
      progressing systemic disease showed significantly increased incidence of LMC,
      whereas the adjuvant chemotherapy reduce the incidence. CONCLUSION: There is an
      increased risk of LMC after SR for PBM from breast cancer compared with WBRT. The
      young age (<40) and systemic burden of cancer in terms of progressing systemic
      disease without adjuvant chemotherapy could be additional risk factors for the
      development of LMC.

PMID- 23115661
TI  - Interobserver and Intraobserver Reliability of Sub-Axial Injury Classification
      and Severity Scale between Radiologist, Resident and Spine Surgeon.
AB  - OBJECTIVE: The sub-axial injury classification (SLIC) and severity scale was
      developed to decide whether to operate the cervical injured patient or not, but
      the reliability of SLIC and severity scale among the different physicians was not
      well known. Therefore, we evaluated the reliability of SLIC among a spine
      surgeon, a resident of neurosurgery and a neuro-radiologist. METHODS: In
      retrograde review in single hospital from 2002 to 2009 years, 75 cases of sub
      axial spine injured patients underwent operation. Each case was blindly reviewed
      for the SLIC and severity scale by 3 different observers by two times with 4
      weeks interval with randomly allocated. The compared axis was the injury
      morphology score, the disco-ligamentous complex score, the neurological status
      score and total SLIC score; the neurological status score was derived from the
      review of medical record. The kappa value was used for the statistical analysis.
      RESULTS: Interobserver agreement of SLIC and severity scale was substantial
      agreement in the score of injury morphology [intraclass correlation (ICC)=0.603]
      and total SLIC and severity sacle (ICC value=0.775), but was fair agreement in
      the disco-ligamentous complex score (ICC value=0.304). Intraobserver agreements
      were almost perfect agreement in whole scales with ICC of 0.974 in a spine
      surgeon, 0.948 in a resident of neurosurgery, and 0.963 in a neuro-radiologist.
      CONCLUSION: The SLIC and severity scale is comprehensive and easily applicable
      tool in spine injured patient. Moreover, it is very useful tool to communicate
      among spine surgeons, residents of neurosurgery and neuro-radiologists with
      sufficient reproducibility.

PMID- 23115662
TI  - Accuracy and Safety in Pedicle Screw Placement in the Thoracic and Lumbar Spines
      : Comparison Study between Conventional C-Arm Fluoroscopy and Navigation Coupled
      with O-Arm(r) Guided Methods.
AB  - OBJECTIVE: The authors performed a retrospective study to assess the accuracy and
      clinical benefits of a navigation coupled with O-arm(r) system guided method in
      the thoracic and lumbar spines by comparing with a C-arm fluoroscopy-guided
      method. METHODS: Under the navigation guidance, 106 pedicle screws inserted from
      T7 to S1 in 24 patients, and using the fluoroscopy guidance, 204 pedicle screws
      from T5 to S1 in 45 patients. The position of screws within the pedicle was
      classified into four groups, from grade 0 (no violation cortex) to 3 (more than 4
      mm violation). The location of violated pedicle cortex was also assessed. Intra
      operative parameters including time required for preparation of screwing
      procedure, times for screwing and the number of X-ray shot were assessed in each
      group. RESULTS: Grade 0 was observed in 186 (91.2%) screws of the fluoroscopy
      guided group, and 99 (93.4%) of the navigation-guided group. Mean time required
      for inserting a screw was 3.8 minutes in the fluoroscopy-guided group, and 4.5
      minutes in the navigation-guided group. Mean time required for preparation of
      screw placement was 4 minutes in the fluoroscopy-guided group, and 19 minutes in
      the navigation-guided group. The fluoroscopy-guided group required mean 8.9 times
      of X-ray shot for each screw placement. CONCLUSION: The screw placement under the
      navigation-guidance coupled with O-arm(r) system appears to be more accurate and
      safer than that under the fluoroscopy guidance, although the preparation and
      screwing time for the navigation-guided surgery is longer than that for the
      fluoroscopy-guided surgery.

PMID- 23115663
TI  - Fragmentectomy versus Conventional Microdiscectomy in Single-Level Lumbar Disc
      Herniations : Comparison of Clinical Results and Recurrence Rates.
AB  - OBJECTIVE: This retrospective study aimed to compare clinical outcomes in terms
      of pain relief and recurrence rate between fragmentectomies and conventional
      microdiscectomies in patients with lumbar disc herniation (LDH). METHODS: Between
      January 2008 and May 2011, a total of 175 patients met the inclusion criteria of
      this study. The visual analogue scale (VAS) scores of back and radicular pains
      were recorded before surgery, 2 and 6 weeks after surgery. Recurrence was defined
      when a patient had the same pattern of preoperative symptoms and was confirmed
      with magnetic resonance imaging. RESULTS: Seventy-four patients (42.3%) were
      suitable for fragmentectomy, and 101 patients underwent conventional
      microdiscectomy. There were no significant differences in VAS scores between the
      fragmentectomy and conventional microdiscectomy groups 2 and 6 weeks after
      surgery. During the follow-up period, 3 patients (4.05%) in the fragmentectomy
      group and 7 patients (6.93%) in the conventional microdiscectomy group relapsed.
      CONCLUSION: If patients are selected according to well-defined criteria,
      fragmentectomy can be a good surgical option for LDH, in the physiological aspect
      of preserving healthy intervertebral disc materials.

PMID- 23115664
TI  - Radiological significance of ligamentum flavum hypertrophy in the occurrence of
      redundant nerve roots of central lumbar spinal stenosis.
AB  - OBJECTIVE: There were previous reports of redundant nerve roots (RNRs) focused on
      their clinical significance and pathogenesis. In this study, we investigated the
      significant radiologic findings that correlate with RNRs occurrence. These
      relations would provide an advanced clue for clinical significance and
      pathogenesis of RNRs. METHODS: Retrospective research was performed with data
      from 126 patients who underwent surgery for central lumbar spinal stenosis (LSS).
      Finally, 106 patients with common denominators (inter-observer accuracy : 84%)
      were included on this study. We divided the patients into two groups by MRI,
      patients with RNRs and those with no RNRs (NRNRs). Comparative analyses were
      performed with clinical and radiologic parameters. RESULTS: RNRs were found in 45
      patients (42%) with central LSS. There were no statistically significant
      differences between the two groups in severity of symptoms. On the other hand, we
      found statistically significant differences in duration of symptom and number of
      level included (p<0.05). In the maximal stenotic level, ligamentum flavum (LF)
      thickness, LF cross-sectional area (CSA), dural sac CSA, and segmental angulation
      are significantly different in RNRs group compared to NRNRs group (p<0.05).
      CONCLUSION: RNRs patients showed clinically longer duration of symptoms and
      multiple levels included. We also confirmed that wide segmental angulation and LF
      hypertrophy play a major role of the development of RNRs in central LSS.
      Together, our results suggest that wide motion in long period contribute to LF
      hypertrophy, and it might be the key factor of RNRs formation in central LSS.

PMID- 23115665
TI  - Surgical outcome of spinal cord hemangioblastomas.
AB  - OBJECTIVE: Spinal cord hemangioblastomas are rare tumors. Despite their benign,
      slow-growing nature, they can cause severe neurological consequences. The purpose
      of this study was to evaluate variable factors, including clinical features,
      tumor findings, the extent of resection, and its recurrence or progression, which
      determine postoperative functional outcomes. METHODS: This study included sixteen
      patients at our institute who underwent microsurgical resection for sporadic
      spinal intramedullary hemangioblastomas and spinal intramedullary
      hemangioblastomas associated with von Hippel-Lindau (VHL) disease, between June
      2003 and March 2012. RESULTS: A total of 30 operations were performed. Total
      resection (TR) of the tumor was achieved in 10 patients, and subtotal resection
      (STR) was achieved in 6. Postoperatively, the initial presenting symptoms were
      improved in 18.7% of the patients and were unchanged in 56.3%, but 25% were
      worse. Stable postoperative neurological functions were found in 83% of patients
      with preoperative McCormick grade I, and TR was achieved in 75% of these
      patients. In the STR group, poorer neurological status was observed in one
      patient, despite multiple operations. There were no poorer outcomes in the four
      cases of VHL disease. Various factors were analyzed, but only a correlation
      between the pre- and postoperative neurological status was verified in the TR
      group patients. CONCLUSION: Preoperative focal neurological impairment and
      meticulous microsurgical manipulation may be predictors of favorable outcomes for
      solitary hemangioblastomas. In addition, the preservation of function is more
      important than the extent of resection in VHL disease.

PMID- 23115666
TI  - Transient adverse neurologic effects of spinal pain blocks.
AB  - OBJECTIVE: Chronic neck or back pain can be managed with various procedures.
      Although these procedures are usually well-tolerated, a variety of side effects
      have been reported. In this study we reviewed cases of unexpected temporary
      adverse events after blocks and suggest possible causes. METHODS: We reviewed the
      records of patients treated with spinal pain blocks between December 2009 and
      January 2011. The types of blocks performed were medial branch blocks,
      interlaminar epidural blocks and transforaminal epidural blocks. During the first
      eight months of the study period (Group A), 2% mepivacaine HCL and triamcinolone
      was used, and during the last six months of the study period (Group B),
      mepivacaine was diluted to 1% with normal saline. RESULTS: There were 704
      procedures in 613 patients. Ten patients had 12 transient neurologic events. Nine
      patients were in Group A and one was in Group B. Transient complications occurred
      in four patients after cervical block and in eight patients after lumbar block.
      Side effects of lumbar spine blocks were associated with the concentration of
      mepivacaine (p<0.05). The likely causes were a high concentration of mepivacaine
      in five patients, inadvertent vascular injection in three patients, intrathecal
      leak of local anesthetics in one, and underlying conversion disorder in one.
      CONCLUSION: Spinal pain blocks are a good option for relieving pain, but
      clinicians should always keep in mind the potential for development of inevitable
      complications. Careful history-taking, appropriate selection of the anesthetics,
      and using real-time fluoroscopy could help reduce the occurrence of adverse
      events.

PMID- 23115667
TI  - Recent changes in risk factors of chronic subdural hematoma.
AB  - OBJECTIVE: Chronic subdural hematoma (CSDH) is a typical disease that is
      encountered frequently in neurosurgical practice. The medications which could
      cause coagulopathies were known as one of the risk factors of CSDH, such as
      anticoagulants (ACs) and antiplatelet agents (APs). Recently, the number of
      patients who are treated with ACs/APs is increasing, especially in the elderly
      population. With widespread use of these drugs, there is a need to study the
      changes in risk factors of CSDH patients. METHODS: We retrospectively reviewed
      290 CSDH patients who underwent surgery at our institute between 1996 and 2010.
      We classified them into three groups according to the time of presentation (Group
      A : the remote period group, 1996-2000, Group B : the past period group, 2001
      2005, and Group C : the recent period group, 2006-2010). Also, we performed the
      comparative analysis of independent risk factors between three groups. RESULTS:
      Among the 290 patients, Group A included 71 patients (24.5%), Group B included 98
      patients (33.8%) and Group C included 121 patients (41.7%). Three patients (4.2%)
      in Group A had a history of receiving ACs/APs, 8 patients (8.2%) in Group B, and
      19 patients (15.7%) in Group C. Other factors such as head trauma, alcoholism,
      epilepsy, previous neurosurgery and underlying disease having bleeding tendency
      were also evaluated. In ACs/APs related cause of CSDH in Group C, significantly
      less proportion of the patients are associated with trauma or alcohol compared to
      the non-medication group. CONCLUSION: In this study, the authors concluded that
      ACs/APs have more importance as a risk factor of CSDH in the recent period
      compared to the past. Therefore, doctors should prescribe these medications
      carefully balancing the potential risk and benefit.

PMID- 23115668
TI  - Transposition of anterior choroidal artery and posterior communicating artery
      origin.
AB  - The anterior choroidal artery has several kinds of variations. Among them, the
      transposition of anterior choroidal artery and posterior communicating artery
      origins has been extremely rare. We report a case with cerebral aneurysm arising
      from posterior communicating artery which origin was distal to the anterior
      choroidal artery and review the relevant literature.

PMID- 23115669
TI  - Spontaneous regression of an unruptured and non-giant intracranial aneurysm.
AB  - It is well known that spontaneous thrombosis in giant cerebral aneurysm is
      common. However, spontaneous obliteration of a non-giant and unruptured cerebral
      aneurysm has been reported to be rare and its pathogenic mechanism is not clear.
      We describe a case with rare vascular phenomenon and review the relevant
      literatures.

PMID- 23115670
TI  - Intracranial extraskeletal myxoid chondrosarcoma : case report and literature
      review.
AB  - Intracranial extraskeletal myxoid chondrosarcoma is extremely rare, with only
      seven patients previously reported. We present a case report of a 21-year-old
      woman admitted for weakness in her right extremities and symptoms of increased
      intracranial pressure. Magnetic resonance imaging (MRI) revealed hydrocephalus
      and a well-enhanced large mass around her left thalamus. A left parietal
      craniotomy and a cortisectomy at the superior parietal lobule were performed.
      Total surgical resection was also performed, and pathology results confirmed an
      extraskeletal myxoid chondrosarcoma. Postoperative MRI showed no residual tumor,
      and the patient underwent radiotherapy. After six months of radiotherapy, the
      patient's headache and weakness had improved to grade IV. This malignant tumor
      showed high rates of recurrence in previous reports. We here report another
      occurrence of this highly malignant and rare tumor in a patient treated using
      total surgical excision and adjuvant radiotherapy.

PMID- 23115671
TI  - Cerebellar liponeurocytoma with an unusually aggressive histopathology : case
      report and review of the literature.
AB  - We report a rare case of cerebellar liponeurocytoma with an unusually aggressive
      histopathology. A 49-year-old man presented with a four-month history of
      headache, vertigo, and progressive swaying gait. Magnetic resonance imaging
      showed a 3*3.5 cm sized relatively well-demarcated round mass lesion in the
      fourth ventricle, characterized by high signal intensity on T2-weighted images.
      Postcontrast images revealed strong enhancement of the solid portion and the cyst
      wall. The patient underwent suboccipital craniectomy and tumor removal. The
      pathologic diagnosis was cerebellar liponeurocytoma. Adjuvant radiotherapy was
      offered due to concerns related to the high proliferative index (Ki-67, 13.68%)
      of the tumor. At the last routine postoperative follow-up visit (12 months), the
      patient complained of no specific symptom and there was no evidence of tumor
      recurrence. However, long-term follow-up and the analysis of similar cases are
      necessary because of the low number of reports and the short follow-up of cases.

PMID- 23115672
TI  - Treatment with epidural blood patch for iatrogenic intracranial hypotension after
      spine surgery.
AB  - Intracranial hypotension syndrome typically occurs spontaneously or
      iatrogenically. It can be associated with headache, drowsy mentality and
      intracranial heamorrhage. Iatrogenic intracranial hypotension can occur due to
      dural pucture, trauma and spine surgery. Treatment may include conservative
      therapy and operation. We report a case of a 54-year-old man who was successfully
      treated with epidural blood patches for intracranial hypotension due to
      cerebrospinal fluid (CSF) leakage into the lumbosacral area after spine surgery.

PMID- 23115673
TI  - Retroperitoneal spinal extradural arachnoid cyst combined with congenital
      hemivertebrae.
AB  - Spinal extradural arachnoid cysts usually cause symptoms related to spinal cord
      or nerve root compression. Here, we report an atypical presentation of a spinal
      extradural arachnoid cyst combined with congenital hemivertebra which was
      presented as a retroperitoneal mass that exerted mass effects to the abdominal
      organs. On image studies, the communication between the cystic pedicle and the
      spinal arachnoid space was indistinct. Based on our experience and the literature
      of the pathogenesis, we planned anterior approach for removal of the arachnoid
      cyst in order to focus on mass removal rather than ligation of the fistulous
      channel. In our estimation this was feasible considering radiologic findings and
      also essential for the symptom relief. The cyst was totally removed with the
      clogged 'thecal sac-side' end of the cystic pedicle. The patient was free of
      abdominal discomfort by one month after the surgery.

PMID- 23115674
TI  - Deep Brain Stimulation of the Globus Pallidus in a 7-Year-Old Girl with DYT1
      Generalized Dystonia.
AB  - The experience of pediatric deep brain stimulation (DBS) of the globus pallidus
      internus (GPi) in the treatment of early-onset DYT1 generalized dystonia is still
      limited. Here, we report the surgical experience of bilateral GPi-DBS under
      general anesthesia by using microelectrode recording in a 7-year-old girl with
      early-onset DYT1 generalized dystonia. Excellent improvement of her dystonia
      without neurological complications was achieved. This case report demonstrates
      that GPi-DBS is an effective and safe method for the treatment of medically
      refractory early-onset DYT1 generalized dystonia in children.

PMID- 23115675
TI  - Bilateral internal superior laryngeal nerve palsy of traumatic cervical injury
      patient who presented as loss of cough reflex after anterior cervical discectomy
      with fusion.
AB  - Injury to the bilateral internal branch of superior laryngeal nerve (ibSLN)
      brings on an impairment of the laryngeal cough reflex that could potentially
      result in aspiration pneumonia and other respiratory illnesses. We describe a
      patient with traumatic cervical injury who underwent bilateral ibSLN palsy after
      anterior cervical discectomy with fusion (ACDF). An 75-year-old man visited with
      cervical spine fracture and he underwent ACDF through a right side approach.
      During the post-operative days, he complained of high pitched tone defect, and
      occasional coughing during meals. With a suspicion of SLN injury and for the work
      up for the cause of aspiration, we performed several studies. According to the
      study results, he was diagnosed as right SLN and left ibSLN palsy. We managed him
      for protecting from silent aspiration. Swallowing study was repeated and no
      evidence of aspiration was found. The patient was discharged with incomplete
      recovery of a high pitched tone and improved state of neurologic status. The SLN
      is an important structure; therefore, spine surgeons need to be concerned and be
      cautious about SLN injury during high cervical neck dissection, especially around
      the level of C3-C4 and a suspicious condition of a contralateral nerve injury.

PMID- 23115676
TI  - Neurotization from two medial pectoral nerves to musculocutaneous nerve in a
      pediatric brachial plexus injury.
AB  - Traumatic brachial plexus injuries can be devastating, causing partial to total
      denervation of the muscles of the upper extremities. Surgical reconstruction can
      restore motor and/or sensory function following nerve injuries. Direct nerve-to
      nerve transfers can provide a closer nerve source to the target muscle, thereby
      enhancing the quality and rate of recovery. Restoration of elbow flexion is the
      primary goal for patients with brachial plexus injuries. A 4-year-old right-hand
      dominant male sustained a fracture of the left scapula in a car accident. He was
      treated conservatively. After the accident, he presented with motor weakness of
      the left upper extremity. Shoulder abduction was grade 3 and elbow flexor was
      grade 0. Hand function was intact. Nerve conduction studies and an electromyogram
      were performed, which revealed left lateral and posterior cord brachial
      plexopathy with axonotmesis. He was admitted to Rehabilitation Medicine and
      treated. However, marked neurological dysfunction in the left upper extremity was
      still observed. Six months after trauma, under general anesthesia with the
      patient in the supine position, the brachial plexus was explored through
      infraclavicular and supraclavicular incisions. Each terminal branch was confirmed
      by electrophysiology. Avulsion of the C5 roots and absence of usable stump
      proximally were confirmed intraoperatively. Under a microscope, neurotization
      from the musculocutaneous nerve to two medial pectoral nerves was performed with
      nylon 8-0. Physical treatment and electrostimulation started 2 weeks
      postoperatively. At a 3-month postoperative visit, evidence of reinnervation of
      the elbow flexors was observed. At his last follow-up, 2 years following trauma,
      the patient had recovered Medical Research Council (MRC) grade 4+ elbow flexors.
      We propose that neurotization from medial pectoral nerves to musculocutaneous
      nerve can be used successfully to restore elbow flexion in patients with brachial
      plexus injuries.

PMID- 23115677
TI  - Treatment of hydrocephalus associated with neurosarcoidosis by multiple shunt
      placement.
AB  - A 31-year-old man was admitted to our hospital due to hydrocephalus with
      neurosarcoidosis. Ventriculo-peritoneal shunting was performed in the right
      lateral ventricle with intravenous methylprednisolone. Subsequently, after 4
      months, additional ventriculo-peritoneal shunting in the left lateral ventricle
      was performed due to the enlarged left lateral ventricle and slit-like right
      lateral ventricle. After 6 months, he was re-admitted due to upward gaze palsy,
      and magnetic resonance image showed an isolated fourth ventricle with both the
      inlet and outlet of fourth ventricle obstructed by recurrent neurosarcoidosis.
      Owing to the difficulty of using an endoscope, we performed neuronavigator-guided
      ventriculo-peritoneal shunting via the left lateral transcerebellar approach for
      the treatment of the isolated fourth ventricle with intravenous methyl
      prednisolone. The patient was discharged with improved neurological status.

PMID- 23115678
TI  - Atypical metronidazole-induced encephalopathy in anaerobic brain abscess.
AB  - Metronidazole-induced encephalopathy is a very rare complication of the long
      standing use of metronidazole. The encephalopathy is bilateral and symmetric in
      nature. We report on the magnetic resonance imaging (MRI) and clinical course of
      metronidazole-induced encephalopathy in a 60-year-old female with a persistent
      anaerobic brain abscess after draining of the abscess. After 3 months of
      metronidazole administration, the patient complained of dysarthria, tingling
      sense of all extremities, and left hemiparesis. MRI revealed symmetric
      hyperintensity lesions in medulla, pons, dentate nuclei of cerebellum, and
      splenium of corpus callosum, all of which represent typical findings of
      metronidazole-induced encephalopathy. In addition, asymmetric lesions in
      midbrain, thalamus, putamen and cerebral subcortical white matter were noted. The
      patient recovered after discontinuation of metronidazole and the remaining
      abscess was successfully treated with meropenem and levofloxacine.

PMID- 23115679
TI  - Does choice of anesthetics affect intraoperative blood loss?

PMID- 23115680
TI  - Cerebral oxygenation monitoring of patients during arthroscopic shoulder surgery
      in the sitting position.
AB  - BACKGROUND: Cerebral hypotension and desaturation can occur during shoulder
      surgery in the seated position. We evaluated the correlation of cerebral oxygen
      saturation (rSO(2)) using near infra-red spectroscopy (NIRS) and mean arterial
      pressures (MAP) (at the levels of the brain and heart). METHODS: Fifty patients,
      scheduled for the arthroscopic shoulder surgery in the seated position, were
      enrolled to monitor the rSO(2), bispectral Index (BIS), and MAPs at the levels of
      the brain and heart. The values of each parameter were collected at 5 min after
      intubation, immediately after placing the patient in the sitting position, 5 min
      after the patient was seated, immediately after the surgical incision, and every
      30 min after incision. RESULTS: A correlation between the cerebral rSO(2) and the
      MAP at the level of brain were statistically significant. Cerebral rSO(2) and MAP
      after a change of posture from supine to sitting position were significantly
      decreased, compared to the baseline value. CONCLUSIONS: Monitoring cerebral
      rSO(2) and MAP at the level of brain can be helpful to detect the possibility of
      cerebral deoxygenation earlier.

PMID- 23115681
TI  - Comparison of surgical conditions during propofol or desflurane anesthesia for
      endoscopic sinus surgery.
AB  - BACKGROUND: Reduction of intraoperative bleeding is necessary to achieve the
      ideal surgical field for the endoscopic sinus surgery (ESS). Intraoperative intra
      nasal bleeding is influenced by various anesthetics. This study compared surgical
      field condition between propofol/remifentanil (PR) based anesthesia and
      desflurane/remifentanil (DR) based anesthesia. METHODS: American Society of
      Anesthesiologists physical status class I or II patients undergoing ESS were
      randomly assigned to group PR (n = 36) or group DR (n = 32). The extent of the
      preoperative surgical lesion was classified as high (> 12) and low (<= 12) Lund
      Mackay (LM) scores according to the computed tomography findings. The target mean
      blood pressure was maintained at 70-80 mmHg. Only one surgeon was involved in
      rating the visibility of the surgical field on a numeric rating scale (NRS) every
      10 minutes. RESULTS: There was a different surgical field grade from PR to DR.
      The mean (SD) surgical field score of NRS for the PR and DR was 2.3 (0.57) and
      2.7 (0.67), respectively (P = 0.006). Especially in the high-LM score patients,
      the mean (SD) of surgical field score for the PR and DR was 2.4 (0.67) and 3.0
      (0.63), respectively (P = 0.012). CONCLUSIONS: In the high-LM score patients, PR
      based anesthesia resulted in better surgical field condition for ESS than DR
      based anesthesia. In ESS, PR based anesthesia is considered to be helpful.

PMID- 23115682
TI  - The effect of low dose ketamine and priming of cisatracurium on the intubating
      condition and onset time of cisatracurium.
AB  - BACKGROUND: Both ketamine and priming may accelerate the onset time of
      neuromuscular blocking agents. We investigate the effect of low dose ketamine and
      cisatracurium priming on the intubating condition and onset time of
      cisatracurium. METHODS: After Institutional Review Board approval, 120
      consecutive patients undergoing general anesthesia were randomly assigned to one
      of 4 groups. All patients were injected one of normal saline (group C),
      cisatracurium 0.01 mg/kg (group P), ketamine 0.5 mg/kg (group K) and combination
      of cisatracurium 0.01 mg/kg, and ketamine 0.5 mg/kg (group PK) diluted into a 5
      ml solution, followed 3 minutes later by cisatracurium 0.15 mg/kg in group C and
      K, and 0.14 mg/kg cisatracurium in priming group. Onset time was recorded the
      electromyographical responses using single twitch and intubating conditions were
      evaluated at 60 seconds after cisatracurium administration. RESULTS: The mean
      onset time was most significantly accelerated in Group PK and was also
      significantly more accelerated in Group P and K compared with Group C (P <
      0.008). It was 112.7 +/- 13.2, 91.4 +/- 17.9, 84.9 +/- 12.7 and 76.4 +/- 8.3
      seconds in Group C, P, K, and PK, respectively. Intubating conditions were
      significantly improved in Group P, K and PK than Group C (P < 0.008). Especially,
      Group PK showed most significant improvement of intubating conditions.
      CONCLUSIONS: The combination of the low dose ketamine and cisatracurium priming
      accelerated the onset time and was improved the intubating conditions.

PMID- 23115683
TI  - The median effective effect-site concentration of remifentanil for minimizing the
      cardiovascular changes to endotracheal intubation during desflurane anesthesia in
      pediatric patients.
AB  - BACKGROUND: Desflurane has the most rapid onset and offset of action among the
      volatile anesthetic agents used for general anesthesia, but it can cause airway
      reactivity, tachycardia, and hypertension during induction, especially in
      pediatric patients. This study was designed to determine a median effective
      effect-site concentration (EC(50)) of remifentanil to prevent the cardiovascular
      changes due to tracheal intubation during the 1 minimum alveolar concentration
      (MAC) desflurane inhalation, which was required to prevent movement in response
      to a noxious stimulus in 50% of subjects, in pediatric patients. METHODS: Twenty
      four pediatric patients between the ages 5-15 years were enrolled in this study.
      We injected thiopental intravenously, at the same time remifentanil was infused
      by Target Controlled Infusion (TCI) device. When the target effect-site
      concentration (Ce) of remifentanil reached a preset level, desflurane was
      administrated through the facial mask. Then, we assessed the signs of desflurane
      related airway reactivity and cardiovascular changes for 2 min. The up-and-down
      criteria was a 20% change in systolic blood pressure (SBP) and a heart rate (HR)
      between just prior to intubation and 1 min after intubation. The EC(50) of
      remifentanil was calculated from 8 independent pairs using Dixon's up-and-down
      method. RESULTS: We studied 24 pediatric patients in range of 1-5 ng/ml of the Ce
      of remifentanil. No patient showed airway reactivity during the study. The EC(50)
      of remifentanil to suppress the hemodynamic changes after tracheal intubation
      during desflurane anesthesia was calculated as 3.4 +/- 0.9 ng/ml. CONCLUSIONS: In
      pediatric anesthesia, the EC(50) of remifentanil to minimize the cardiovascular
      changes due to tracheal intubation during 1 MAC desflurane anesthesia was 3.4 +/-
      0.9 ng/ml.

PMID- 23115684
TI  - Comparison of clinical effects according to the dosage of sufentanil added to
      0.5% hyperbaric bupivacaine for spinal anesthesia in patients undergoing cesarean
      section.
AB  - BACKGROUND: Subarachnoid block is a widely used technique for cesarean section.
      To improve the quality of analgesia and prolong the duration of analgesia,
      addition of intrathecal opioids to local anesthetics has been encouraged. We
      compared the effects of sufentanil 2.5 ug and 5 ug, which were added to
      intrathecal hyperbaric bupivacaine. METHODS: We enrolled 105 full term
      parturients were randomly divided into 3 groups: Group 1 (control), Group 2
      (sufentanil 2.5 ug), and Group 3 (sufentanil 5 ug). In every group, 0.5% heavy
      bupivacaine was added according to the adjusted dose regimen. We determined the
      maximum level of sensory block and motor block, the quality of intraoperative
      analgesia, the duration of effective analgesia and side effects. RESULTS: There
      were no significant differences among the 3 groups in the maximum level of the
      sensory block and motor block. Recovery rate of the sensory block, however, was
      significantly slower in Group 3 than Group 1. Quality of intraopertive analgesia,
      muscle relaxation, and duration of effective analgesia were enhanced by
      increasing the dosage of intrathecal sufentanil. Frequencies of hypotension,
      maximum sedation level, and pruritus were directly related to the dosage of
      intrathecal sufentanil, whereas nausea and vomiting occurred only in the groups
      using sufentanil. CONCLUSIONS: The addition of sufentanil 2.5 ug for spinal
      anesthesia provides adequate intraoperative analgesia and good postoperative
      analgesia with minimal adverse effects on the mother.

PMID- 23115685
TI  - The EC(50) of remifentanil to minimize the cardiovascular changes during head
      holder pinning in neurosurgery.
AB  - BACKGROUND: During neuroanesthesia, head holder pinning commonly results in
      sympathetic stimulation manifested by hemodynamic changes, such as increased
      heart rate and arterial blood pressure. Remifentanil has been used successfully
      to control acute autonomic responses during neurosurgical procedures. The
      objective of this study was to determine effect-site concentration of
      remifentanil for suppressing the hemodynamic response to head holder pinning with
      the probability of 50% (EC(50)). METHODS: Forty-one ASA physical status I or II
      patients, between the ages of 20-70, who were scheduled for neurosurgery were
      recruited into this study. After arrival in the operating room, standard
      monitoring was applied throughout the study, which included a bispectral index
      monitor. Both propofol and remifentanil were administered by Target-control
      infusion device. The Dixon "up-and-down" sequential allocation method was used to
      determine the EC(50) of remifentanil. RESULTS: The EC(50) of remifentanil was
      2.19 +/- 0.76 ng/ml by the turning point estimate (TPE). In probit analysis,
      EC(50) was 2.42 ng/ml (95% CI : -0.62-4.66) and EC(95) was 5.70 ng/ml (95% CI :
      4.02-67.53). The EC(50) estimator comes from isotonic regression is 2.90 ng/ml
      (95% CI : 1.78-3.65). The EC(95) estimator comes from isotonic regression is 4.28
      ng/ml (95% CI : 3.85-4.41). CONCLUSIONS: This study showed that EC(50) of
      remifentanil was 2.19 +/- 0.76 ng/ml by TPE. EC(50) was 2.42 ng/ml (95% CI -0.62
      4.66) in probit analysis, as back up analysis. The EC(50) estimator comes from
      isotonic regression is 2.90 ng/ml (95% CI : 1.78-3.65).

PMID- 23115686
TI  - The comparative study to evaluate the effect of palonosetron monotherapy versus
      palonosetron with dexamethasone combination therapy for prevention of
      postoperative nausea and vomiting.
AB  - BACKGROUND: 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists are effective
      and safe on postoperative nausea and vomiting (PONV). Palonosetron, the newest 5
      HT3 antagonist, has potent antiemetic property. We hypothesized that a
      combination of palonosetron and dexamethasone could more decrease PONV than
      palonosetron alone. METHODS: Among the patients scheduled to undergo laparoscopic
      gynecologic surgery, mastoidectomy with tympanoplasty or thyroidectomy under
      general anesthesia, eighty four female patients with at least two PONV risk
      factors were enrolled in this study. They were received randomly 0.075 mg
      palonosetron and 4 mg dexamethasone (group C) or 0.075 mg palonosetron alone
      (group P). The severity of PONV using Rhodes index and the percentage of complete
      response during postoperative 24 hours were compared between groups. RESULTS: The
      frequency of mild/moderate/great/severe PONV based on Rhodes index were
      9.8%/0%/0%/0% and 9.3%/2.3%/2.3%/0% in group P and group C, respectively.
      Complete response for PONV was observed in 90.2% and 86% of patients in group P
      and group C, respectively. The overall incidence of PONV in group P and C was
      9.8% and 14%, respectively. There was no significant difference between the two
      groups. CONCLUSIONS: There were no differences between palonosetron monotherapy
      and combination therapy of palonosetron and dexamethasone in patients with high
      emetogenic risk.

PMID- 23115687
TI  - Polyphenol (-)-epigallocatechin gallate-induced cardioprotection may attenuate
      ischemia-reperfusion injury through adenosine receptor activation: a preliminary
      study.
AB  - BACKGROUND: The activation of guanine nucleotide binding protein-coupled
      receptors, such as adenosine receptor (ADR) and opioid receptor (OPR), protects
      the heart against ischemia and reperfusion injury. We hypothesized that ADR or
      OPR might be involved in polyphenol (-)-epigallocatechin gallate (EGCG)-induced
      cardioprotection. METHODS: Langendorff perfused rat hearts were subjected to 30
      min of regional ischemia and 2 h of reperfusion. Hearts were treated with 10 uM
      of EGCG, with or without the ADR or OPR antagonist at early reperfusion. Infarct
      size measured with 2,3,5-triphenyltetrazolium chloride staining was chosen as end
      point. RESULTS: EGCG significantly reduced infarct volume as a percentage of
      ischemic volume (33.5 +/- 4.1%) compared to control hearts (14.4 +/- 1.1%, P <
      0.001). A nonspecific ADR antagonist 8-(p-sulfophenyl) theophylline hydrate (27.1
      +/- 1.9%, P < 0.05 vs. EGCG) but not a nonspecific OPR antagonist naloxone (14.3
      +/- 1.3%, P > 0.05 vs. EGCG) blocked the anti-infarct effect by EGCG. The infarct
      reducing effect of EGCG was significantly reversed by 200 nM of the A(1) ADR
      antagonist DPCPX (25.9 +/- 1.1%, P < 0.05) and 15 nM of the A(2B) ADR antagonist
      MRS1706 (29.3 +/- 1.7%, P < 0.01) but not by 10 uM of the A(2A) ADR antagonist
      ZM241385 (23.9 +/- 1.9%. P > 0.05 vs. EGCG) and 100 nM of the A(3) ADR antagonist
      MRS1334 (24.1 +/- 1.8%, P > 0.05). CONCLUSIONS: The infarct reducing effect of
      EGCG appears to involve activation of ADR, especially A(1) and A(2B) ADR, but not
      OPR.

PMID- 23115688
TI  - The effect of positive-end expiratory pressure on oxygenation during high
      frequency jet ventilation and conventional mechanical ventilation in the rabbit
      model of acute lung injury.
AB  - BACKGROUND: The use of positive end expiratory pressure (PEEP) in patients with
      acute lung injury (ALI) improves arterial oxygenation by alleviating pulmonary
      shunting, helping the respiratory muscles to decrease the work of breathing,
      decreasing the rate of infiltrated and atelectatic tissues, and increasing
      functional residual capacity. In a rabbit model of saline lavage-induced ALI, we
      examined the effects of PEEP on gas exchange, hemodynamics, and oxygenation
      during high frequency jet ventilation (HFJV), and then compared these parameters
      with those during conventional mechanical ventilation (CMV). METHODS: Twelve
      rabbits underwent repeated saline lavage to create ALI. The animals were divided
      in 2 groups: 1) Group CMV (n = 6), and 2) Group HFJV (n = 6). In both groups, we
      applied 2 levels of PEEP (5 cmH(2)O and 10 cmH(2)O) and then measured the
      arterial blood gas, mixed venous blood gas, and hemodynamic parameters. RESULTS:
      With administration of PEEP of either 5 cmH(2)O or 10 cmH(2)O, the arterial
      oxygen content of both groups was increased, although without statistically
      significant differences between groups. On the contrary, the arterial carbon
      dioxide content was significantly decreased in the HFJV group, as compared with
      the CMV group, during the entire experiment. Furthermore, there was significant
      decreases in mean arterial pressures in both groups with a PEEP of 10 cmH(2)O.
      CONCLUSIONS: The application of PEEP in rabbits with ALI effectively improves
      oxygenation in either HFJV or CMV.

PMID- 23115689
TI  - A case of acute hemolytic transfusion reaction due to anti-Di(a) antibody -A case
      report-.
AB  - Many medical institutions in Korea have recently been performing an antibody
      screening test as one of the essential elements of a pre-transfusion test. The
      Di(a) antigen is well known as one of the antigens with low incidence among
      Caucasians; however, it has been discovered with a relatively higher incidence
      among Mongoloid populations. The frequency of the Di(a) antigen among the Korean
      population is estimated to be 6.4-14.5%. But in Korea, a screening panel of cells
      from abroad without Di(a) positive cells has been commonly used when a patient
      has an unexpected antibody screening test. Here we report a case of acute
      hemolytic transfusion reaction due to Anti-Di(a) antibody. To prevent other
      transfusion reaction by anti-Di(a) antibody, addition of Di(a) positive cells as
      unexpected antibody screening test is recommended.

PMID- 23115690
TI  - Epidural anesthesia for laparoscopic cholecystectomy in a patient with sickle
      cell anemia, beta thalassemia, and Crohn's disease -A case report-.
AB  - A 37-year-old woman diagnosed with sickle cell anemia (SCA), beta (+)
      thalassemia, Crohn's disease, and liver dysfunction was scheduled for
      laparoscopic cholecystectomy (LC) due to acute cholecystitis with gall bladder.
      Regional anesthesia was performed. An epidural catheter was inserted into the 9
      10 thoracal epidural space and then 15 ml of 0.5% bupivacaine was injected
      through the catheter. The level of sensorial analgesia tested with pinprick test
      reached up to T4. Here we describe the first case of the combination of sickle
      cell anemia (SCA), beta (+) thalassemia, and Crohn's disease successful
      anesthetic management with attention to hemodynamics, particularly with regards
      to liver dysfunction.

PMID- 23115691
TI  - Emergency cesarean delivery in a parturient who had an intractable paroxysmal
      supraventricular tachycardia -A case report-.
AB  - Paroxysmal supraventricular tachycardia (SVT) is a common arrhythmia in the
      parturient and can occur with or without an underlying organic heart disease. A
      woman of 35 weeks' gestation, who had a paroxysmal SVT that was resistant to
      antiarrhythmic drugs and electric cardioversion, required emergency Cesarean
      delivery. The Cesarean delivery was performed under spinal anesthesia and a
      healthy baby was delivered uneventfully. SVT spontaneously converted to normal
      sinus rhythm right after delivery of the baby.

PMID- 23115692
TI  - Anesthetic course and complications that were encountered during endoscopic
      thyroidectomy -A case report-.
AB  - Endoscopic thyroidectomy is gaining popularity, but it can increase the risk of
      certain complications. Carbon dioxide insufflation in the neck may cause adverse
      effects on hemodynamic and ventilatory aspects. We report the anesthetic course
      and complications that were encountered during endoscopic thyroidectomy. Although
      the surgery was successful, the patient developed signs of hypercarbia,
      subcutaneous emphysema and pneumothorax.

PMID- 23115693
TI  - Neurogenic pulmonary edema following intracranial coil embolization for
      subarachnoid hemorrhage -A case report-.
AB  - Neurogenic pulmonary edema (NPE) is a well-known complication of acute central
      neurologic injury, particularly aneurysmal subarachnoid hemorrhage. Both
      increased intracranial pressure and severe over-activation of the sympathetic
      nervous system seem to be pathogenetic for the onset of NPE. Although
      intracranial endovascular therapy is minimally invasive, it may affect brain stem
      regions and result in sympathetic activation. We now report the case of a 70-year
      old woman who suddenly developed pulmonary edema during coil embolization of a
      ruptured aneurysm. During the intervention, oxygen saturation declined suddenly
      and a chest radiograph revealed pulmonary edema. The delayed appearance of NPE in
      this patient implies a risk for sympathetically mediated NPE during endovascular
      therapy.

PMID- 23115694
TI  - Falsely increased bispectral index score during deep hypothermic circulatory
      arrest in cardiac surgery.

PMID- 23115695
TI  - An undiagnosed pseudoaneurysm found during arterial catheterization in a Takayasu
      arteritis patient.

PMID- 23115696
TI  - Phantom bladder pain.

PMID- 23115697
TI  - A suspected case of malignant hyperthermia that was successfully treated with
      dantrolene administration via nasogastric tube.

PMID- 23115698
TI  - Systematic review research in family medicine.

PMID- 23115699
TI  - Factors of compliance in patients with hypercholesterolemia using rosuvastatin in
      primary care.
AB  - BACKGROUND: In order to evaluate the factors of compliance with a lipid lowering
      therapy, a prospective observational study of patients with hypercholesterolemia
      using rosuvastatin was carried out. METHODS: A total of 2,607 patients who were
      newly prescribed rosuvastatin were enrolled from 32 family physicians in Korea
      from March 2009 to December 2009. Of them, 301 patients were excluded due to
      incomplete data or follow-up compliance data. The patients were regularly
      observed to ascertain the compliance associated with rosuvastatin at intervals of
      12 and 24 weeks. We collected risk factors for the compliance using a structured
      questionnaire. The criteria for evaluating compliance are to measure clinic
      attendance, to assess the continuity of therapy, and to calculate the percentage
      of doses taken. RESULTS: Among a total of 2,306 patients, the degree of
      compliance was 54.1%. According to logistic regression analysis, the factors for
      compliance with the lipid lowering drug included old age (odds ratio [OR], 2.68;
      95% confidence interval [CI], 2.09 to 3.45), frequent exercise (OR, 1.76; 95% CI,
      1.43 to 2.18), previous statin therapy (OR, 4.02; 95% CI, 3.22 to 5.01),
      hypertension (OR, 1.80; 95% CI, 1.48 to 2.19), diabetes mellitus (OR, 2.20; 95%
      CI, 1.69 to 2.87), concomitant medication (OR, 2.28; 95% CI, 1.88 to 2.77), and
      high coronary heart disease (CHD) risk category (OR, 1.82; 95% CI, 1.39 to 2.38).
      The compliance decreased with high low density lipoprotein cholesterol levels
      (OR, 0.20; 95% CI, 0.16 to 0.26). CONCLUSION: The compliance of patients using
      rosuvastatin was 54.1% in primary care. The factors related to higher compliance
      were old age, regular exercise, previous statin therapy, concomitant medication,
      presence of hypertension or diabetes, and higher CHD risk level.

PMID- 23115700
TI  - A Comparison of Efficacy and Safety of Non-steroidal Anti-inflammatory Drugs
      versus Acetaminophen in the Treatment of Episodic Tension-type Headache: A Meta
      analysis of Randomized Placebo-controlled Trial Studies.
AB  - BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen are
      widely used in the treatment of tension headache. The objective of this study was
      to evaluate and compare the efficacy and safety of single doses of acetaminophen
      and NSAIDs using meta-analysis of randomized placebo-controlled trial studies.
      METHODS: We searched MEDLINE, EMBASE, CINAHL, Cochrane, KMbase, KoreaMed, RiCH,
      National Assembly Library, Riss4u, and DBPIA for studies released through 27th
      July 2010. Two authors independently extracted the data. To assess the risk of
      bias, the Cochrane Collaborations risk of bias tool was used. Review Manager 5.0
      was used for statistics. RESULTS: We identified 6 studies. The relative benefit
      of the NSAIDs group compared to the acetaminophen group for participants with at
      least 50% pain relief was 1.18 (95% confidence interval [CI], 0.99 to 1.39; I(2)
      = 85%). We did subgroup analysis based on allocation concealment versus non
      allocation concealment, and low-dose NSAIDs versus high-dose NSAIDs. The relative
      benefit of the low-dose NSAIDs subgroup to the acetaminophen group was 0.98 (95%
      CI, 0.91 to 1.06; I(2) = 0%). However, the heterogeneity of other subgroup
      analysis was not settled. The relative risk for using rescue medication of the
      NSAIDs group compared to the acetaminophen group was 0.84 (95% CI, 0.64 to 1.12;
      I(2) = 47%). The relative risk for adverse events was 1.31(95% CI, 0.96 to 1.80;
      I(2) = 0%). CONCLUSION: In this meta-analysis, there was no difference between
      low-dose NSAIDs and acetaminophen in the efficacy of the treatment for tension
      type headache. The results suggested that high-dose NSAIDs have more effect but
      also have more adverse events. The balance of benefit and harm needs to be
      considered when using high-dose NSAIDs for tension headache.

PMID- 23115701
TI  - Use of Proton Pump Inhibitor and Risk of Colorectal Cancer: A Meta-analysis of
      Observational Studies.
AB  - BACKGROUND: Previous case-control studies have reported inconsistent findings
      regarding the association between proton pump inhibitor (PPI) use and colorectal
      cancer (CRC) risk. We investigated these associations using meta-analysis.
      METHODS: We searched MEDLINE (PubMed), EMBASE, and the Cochrane Library in April
      2011. Two evaluators independently reviewed and selected articles, based on pre
      determined selection criteria. RESULTS: Out of 737 articles meeting our initial
      criteria, 5 case-control studies, which involved 120,091 participants (9,514
      cases and 110,577 controls), were included in the final analyses. The overall use
      of PPI (used vs. never or rarely used) was not significantly associated with the
      risk of CRC in a fixed-effects model meta-analysis of all 5 case-control studies
      (odds ratio [OR], 1.08; 95% confidence interval [CI], 0.96 to 1.20; I(2) = 3.5%).
      Also, in sensitivity meta-analysis by cumulative duration of PPI use, there was
      no association between PPI use of 1 year or longer and the risk of colorectal
      cancer in a fixed-effects meta-analysis (OR, 1.09; 95% CI, 0.98 to 1.22; I(2) =
      0%). CONCLUSION: Although hypergastrinemia could be an important factor in the
      pathogenesis of some colorectal cancers, our study suggests that this does not
      lead to significant clinical risk for most PPI users. Further prospective studies
      or randomized controlled trials related to PPI use and colorectal cancer risk are
      needed to investigate this association.

PMID- 23115702
TI  - Relationship between Food-frequency and Glycated Hemoglobin in Korean Diabetics:
      Using Data from the 4th Korea National Health and Nutrition Examination Survey.
AB  - BACKGROUND: This study was performed to evaluate the association between food
      intake frequencies and long-term blood glucose control using glycated hemoglobin
      (HbA1c) in Korean diabetes. METHODS: This study used data collected from the 4th
      Korea National Health and Nutrition Examination Survey. Patients with diabetes
      were defined as people who responded "yes" to the question "Are you currently
      suffering from diabetes?" or in whom serum fasting glucose was 126 mg/dL or more.
      Using the food frequency questionnaire and HbA1c in surveys, we examined the
      association between the annual food-frequencies of each food group and long-term
      blood glucose control. RESULTS: After adjustment for other covariates, HbA1c
      decreased significantly as the frequency of the intake of fish increased in each
      population (P = 0.001 for all, P = 0.043 for men, P = 0.001 for women). The
      intake of mackerel played an especially important role in the control of
      diabetes. Among women, HbA1c decreased as the frequency of intake of legumes
      increased (P = 0.029) and increased as the frequency of intake of staple
      carbohydrates increased (P = 0.015). On the other hand, any intake of other food
      groups showed no significant relationship with HbA1c. CONCLUSION: Frequent intake
      of fish in all populations and legumes in woman were associated with good
      glycemic control in diabetics. Frequent intake of carbohydrates was associated
      with elevated HbA1c in women.

PMID- 23115703
TI  - Bone Mineral Density and Food-frequency in Korean Adults: The 2008 and 2009 Korea
      National Health and Nutrition Examination Survey.
AB  - BACKGROUND: Diet and Nutrition are important modulators of bone health in men and
      women. We investigated the associations between frequency of food intake among
      certain food groups and bone mineral density (BMD) in a large population of
      Korean adults. METHODS: We used the data from Korea National Health and Nutrition
      Examination Survey during 2008 to 2009. Participants were aged 20 years and over.
      BMDs were measured at lumbar spine and femoral neck with dual-energy X-ray
      absorptiometry. Dietary and supplement intakes were assessed by food-frequency
      questionnaire. We used multiple linear regression analysis to evaluate the
      relationships between annual food-frequency of each food group and BMD. RESULTS:
      After adjustment of multiple covariates, femoral neck and lumbar BMD
      significantly increased as the frequency of fruit consumption increased in both
      men and women. Frequency of other carbohydrates consumption was significantly
      associated with greater femoral neck and lumbar BMD for women. Frequency of milk
      and dairy product consumption was significantly associated with greater femoral
      neck BMD in men. Other food groups, however, had no significant associations with
      BMDs. CONCLUSION: Frequent consumption of fruit has a positive association with
      BMDs in men and women. Milk and dairy products and other carbohydrates also had
      positive effects on BMD for men and women, respectively.

PMID- 23115704
TI  - Assessment of lifestyle effects on the levels of free oxygen radicals in the
      korean population.
AB  - BACKGROUND: As many studies revealed that oxidative stress due to the imbalance
      of reactive oxygen species (ROS) and antioxidant capacity is related with
      pathologic processes such as cardiovascular diseases, diabetes, as well as aging
      and obesity, the relationship between lifestyle and oxidative stress has recently
      gained much medical attention. However, little information exists on the effects
      of lifestyle on ROS in Korea. In this study, we investigated the effects of
      lifestyle on free oxygen radical levels in men and women in Korea. METHODS: A
      total of 138 adults participated in this study from September 2007 to June 2010
      at a health promotion center and department of family medicine. Information on
      the lifestyle of each participant was obtained by questionnaire. Biochemical
      markers and a free oxygen radical test (FORT) were also measured. RESULTS: The
      average age was 47.28 +/- 10.85 years and 79.7% were male. High sensitivity C
      reactive protein (hs-CRP; r = 0.418, P = 0.012), triglycerides (r = -0.243, P =
      0.008), hemoglobin (r = -0.445, P < 0.001), total protein (r = 0.210, P = 0.036),
      creatinine (r = -0.294, P = 0.001), fruit intake per day (P = 0.047), and smoking
      (P = 0.003) were related to the FORT levels in univariate analysis. Multiple
      linear regression analysis showed that hs-CRP (P = 0.039) was an independent
      predictor of serum FORT values. This statistical model can explain 78% of the
      variance in FORT values. CONCLUSION: This result suggests that hs-CRP showed a
      statistically significant positive association with FORT values. Further studies
      on the relationship between lifestyle and antioxidant capacity as well as ROS
      seem to be warranted to evaluate the overall effect of oxidative stress.

PMID- 23115705
TI  - Changes in the Serum Level of High Density Lipoprotein-cholesterol after Smoking
      Cessation among Adult Men.
AB  - BACKGROUND: Smoking and obesity are known risk factors for cardiovascular
      diseases, while low serum levels of high density lipoprotein-cholesterol is an
      independent risk factor for mortality from ischemic heart diseases. This study
      examines changes in the serum level of high density lipoprotein-cholesterol
      depending on changes in the state of smoking and body mass index. METHODS: A
      survey and blood check-up were conducted on medical examination, along with acts
      of smoking among male adults of 25 years or older who visited the health
      promotion center of Daegu Medical Center from 2007 to 2010, and the results were
      analyzed. The subjects were divided into two different groups, current smokers
      and abstainers, and body mass index, total cholesterol, high density lipoprotein
      cholesterol, low density lipoprotein-cholesterol, and triglycerides for three
      years were compared in both groups. Changes between the first and second visits
      in body mass index and lipid profiles of the two groups were compared to analyze
      changes after abstaining. RESULTS: The subject group which showed a significant
      increase in high density lipoprotein-cholesterol level was only abstainers whose
      body mass index had decreased by more than 0.5 kg/m(2). CONCLUSION: Smoking
      cessation increases serum levels of high density lipoprotein-cholesterol. If
      reduction of body mass index and smoking cessation are combined, the risk of
      cardiovascular disease will be lower in proportion to the increase in serum high
      density lipoprotein.

PMID- 23115706
TI  - Relationship between Occupational Stress and Gastric Disease in Male Workers.
AB  - BACKGROUND: Physical and mental health of workers is threatened due to various
      events and chronic occupational stress. This study was conducted to investigate
      the relationship between occupational stress and gastric disease in male workers
      of the shipbuilding industry. METHODS: Occupational stress measured among a total
      of 498 workers of a shipbuilding firm who visited the hospital for health
      examination using the Korean Occupational Stress Scale (KOSS)-short form, and the
      relationship between sociodemographic factors, health-related behaviors,
      occupational stress, and gastric disease, and the distribution of occupational
      stress by sociodemographic factors in the gastric disease group was examined.
      RESULTS: There was no significant association between gastric disease and total
      occupational stress score and its seven sub-factors. The analysis showed that
      risk of gastric disease was significantly higher in the Q1 group in which the
      stress caused by occupational discomfort among seven sub-factors was lowest than
      that in the Q4 group (odds ratio, 2.819; 95% confidence interval, 1.151 to
      6.908). Analysis only on the gastric disease group showed that the stress score
      of laborers was higher in the four sub-factors than that of office workers (P <
      0.05). Analysis on educational background showed that the scores of the three sub
      factors were lower in subjects who's highest level of education was high school
      (P < 0.01). CONCLUSION: This study suggests that it is necessary to improve the
      culture of Korean collectivism in the workplace and to manage the occupational
      stress in the low-educated and laborers. It is recommended for future studies to
      confirm the causal relationship between occupational stress and gastric disease
      by large scale studies using a KOSS which appropriately reflects workplace
      culture.

PMID- 23115707
TI  - Improved chronic fatigue symptoms after removal of mercury in patient with
      increased mercury concentration in hair toxic mineral assay: a case.
AB  - Clinical manifestations of chronic exposure to organic mercury usually have a
      gradual onset. As the primary target is the nervous system, chronic mercury
      exposure can cause symptoms such as fatigue, weakness, headache, and poor recall
      and concentration. In severe cases chronic exposure leads to intellectual
      deterioration and neurologic abnormality. Recent outbreaks of bovine spongiform
      encephalopathy and pathogenic avian influenza have increased fish consumption in
      Korea. Methyl-mercury, a type of organic mercury, is present in higher than
      normal ranges in the general Korean population. When we examine a patient with
      chronic fatigue, we assess his/her methyl-mercury concentrations in the body if
      environmental exposure such as excessive fish consumption is suspected. In the
      current case, we learned the patient had consumed many slices of raw tuna and was
      initially diagnosed with chronic fatigue syndrome. Therefore, we suspected that
      he was exposured to methyl-mercury and that the mercury concentration in his hair
      would be below the poisoning level identified by World Health Organization but
      above the normal range according to hair toxic mineral assay. Our patient's toxic
      chronic fatigue symptoms improved after he was given mercury removal therapy,
      indicating that he was correctly diagnosed with chronic exposure to organic
      mercury.

PMID- 23115708
TI  - Comments on statistical issues in september 2012.

PMID- 23115709
TI  - The fruit of Bursera: structure, maturation and parthenocarpy.
AB  - BACKGROUND AND AIMS: The deterioration of seasonally tropical dry forests will
      stop with the implementation of management plans for this ecosystem. To develop
      these plans, we require information regarding aspects such as germination and the
      presence of 'empty seeds' of representative species-like, for example, Bursera, a
      genus with a high number of endemic species of the Mesoamerican Hotspot-that
      would enable us to propagate its species. The main purpose of this study is to
      describe the phenological and structural characteristics of fruits of 12 Bursera
      species and provide useful data for future studies on germination and seed
      dispersal, and to acquire new and useful information to understand the
      phylogenetic relationships of the Burseraceae family. METHODOLOGY: We described
      the phenology of fruit ripening in 12 species of Bursera. Fruits were collected
      from the study sites in three different stages of development. The histochemical
      and anatomical characteristics of fruits of all species were described with the
      use of inclusion techniques and scanning microscopy. PRINCIPAL RESULTS: There is
      a time gap between the development of the ovary and the development of the ovule
      in the 12 studied species. The exposed pseudoaril during the dispersion stage is
      an indicator of the seed's maturity and the fruit's viability. The Bursera fruit
      shows the same structural pattern as that of Commiphora, as well as many
      similarities with species of the Anacardiaceae family. All species develop
      parthenocarpic fruits that retain the structural characteristics of the immature
      fruits: soft tissues rich in nitrogen compounds and few chemical and physical
      defences. Insects were found mainly inside the parthenocarpic fruits in eight
      species of Bursera. CONCLUSIONS: The dispersion unit in Bursera consists of a
      seed, a lignified endocarp that protects the seed, and a pseudoaril that helps
      attract seed dispersers. The production of parthenocarpic fruits is energy
      saving; however, it is necessary to evaluate the potential benefits of this
      phenomenon.

PMID- 23115710
TI  - Approaches towards nitrogen- and phosphorus-efficient rice.
AB  - BACKGROUND AND AIMS: Food production has to increase to meet the demand of a
      growing population. In light of the high energy costs and increasingly scarce
      resources, future agricultural systems have to be more productive and more
      efficient in terms of inputs such as fertilizer and water. The development of
      rice varieties with high yield under low-nutrient conditions has therefore become
      a breeding priority. The rapid progress made in sequencing and molecular-marker
      technology is now beginning to change the way breeding is done, providing new
      opportunities. SCOPE: Nitrogen (N) and phosphorus (P) are applied to agricultural
      systems in large quantities and a deficiency of either nutrient leads to yield
      losses and triggers complex molecular and physiological responses. The underlying
      genes are now being identified and studied in detail, and an increasing number of
      quantitative trait loci (QTLs) related to N and P uptake and utilization are
      being reported. Here, we provide an overview of the different aspects related to
      N and P in rice production systems, and apply a breeder's perspective on the
      potential of relevant genes and pathways for breeding applications. MAIN POINTS:
      For the development of nutrient-efficient rice, a holistic approach should be
      followed combining optimized fertilizer management with enhanced nutrient uptake
      via a vigorous root system, leading to increased grain filling and yield. Despite
      an increasing number of N- and P-related genes and QTLs being reported, very few
      are actively used in molecular breeding programmes. The complex regulation of N-
      and P-related pathways challenges breeders and the research community to identify
      large-effect genes/QTLs. For this it will be important to focus more on the
      analysis of tolerant genotypes rather than model plants, since tolerance pathways
      may employ a different set of genes.

PMID- 23115711
TI  - The unfolding treatment landscape for men with castration-resistant prostate
      cancer.
AB  - Castration-resistant prostate cancer (CRPC) is a fatal disease in virtually all
      patients. Docetaxel chemotherapy became the standard front-line agent based on
      the results of the TAX327 trial in 2004, with a survival advantage of 3 months
      achieved over mitoxantrone. Over the past few years, an improved understanding of
      the molecular biology of castration-resistance has resulted in expansion of the
      treatment armamentarium for advanced prostate cancer with the emergence of novel
      androgen receptor-directed therapies, cytotoxic chemotherapies, as well as
      immunotherapies. Four different agents have very recently gained approval by the
      U.S. Food and Drug Administration for the treatment of CRPC and this review will
      summarize the development, mechanism of action, and safety and efficacy of these
      agents as demonstrated in preclinical as well as clinical studies.

PMID- 23115712
TI  - Establishment of a standard seed lot system of an Iranian Mumps virus strain; RS
      12, for mass production of mumps and MMR vaccines.
AB  - BACKGROUND: At present the mumps virus strain used for production of mumps
      vaccine for our local use is Hoshino strain. However, according to our National
      public health policies, this strain should be replaced with a safer strain. Based
      on our previous data, the Iranian mumps strain; RS-12 has been proved to be the
      most suitable alternative to Hoshino strain with little or no adverse events
      following vaccination METHODS: The aim of the present study was to optimize
      propagation of RS-12 strain and prepare standard seeds for vaccine mass
      production. The virus was inoculated to cells using different methods and
      different multiplicity of infection (MOI). The viral suspensions were harvested
      using different methods. Quality control tests were run at different stages.
      RESULTS: Maximum viral yield was achieved when cell suspensions were inoculated
      at MOI of 1:10 and incubated at 36-37oC for 48 hours, followed by replacement of
      the media and incubation at 33-34 oC for 5-7 days. Filtration did not affect the
      viral titre. A standard seed lot system was successfully established and
      experimental batches of MMR vaccines were produced. CONCLUSION: The established
      seed lot system has met all requirements of WHO regulations and could be used in
      mass production of safe and efficacious mumps and MMR vaccines. Clinical trials
      are in progress for this newly produced vaccine.

PMID- 23115713
TI  - Efficacy of omega-3 fatty acids supplementation in treatment of uremic pruritus
      in hemodialysis patients: a double-blind randomized controlled trial.
AB  - BACKGROUND: Uremic pruritus is a common and bothersome complaint among end-stage
      renal disease which affect between 25% and 60% of this population .But there is
      no decisive cure for treatment of it. In this study, the effects of omega-3 for
      treatment of pruritus were investigated in hemodialysis patients. METHODS: A
      double-blind randomized study was carried out in the form of placebo-controlled
      crossover study in four dialysis centers in Tehran, Iran during 2008. At first,
      22 hemodialysis patients suffering from pruritus with previous drug resistance
      were selected. Next, these patients were randomly allocated into two groups of
      omega-3-placebo (group A) and placebo-omega-3 (group B) .Patients in group A were
      treated with a 1-gram Fish oil capsule for 20 days, and subsequently, they were
      treated with placebo for 20 days after a 14-day wash-out period .But the reverse
      act was done in group B.The pruritus assessment was made quantitatively through
      Detailed Pruritus Score. RESULTS: Pruritus was decreased up to 65% from score
      mean of 20.3 (95% CI: 16.7-23.8) to 6.4 (95% CI: 2.9-9.8) in omega-3 group and
      the decrease in the placebo group was 15% from score mean of 17.0 (95% CI: 12.4
      21.6) to 14.4 (95% CI: 10.5-18.2).So the level of statistical difference was
      significant (P=0.0001). DISCUSSION: Omega-3 fatty acids found to be more
      effective than placebo in decreasing of uremic pruritus. So it seems that Omega-3
      fatty acids could be used as an efficient drug for treatment of pruritus in
      uremic patients.

PMID- 23115714
TI  - The Efficacy of Percutaneous Vertebroplasty in Pain Relief in Patients with
      Pathological Vertebral Fractures due to Metastatic Spinal Tumors.
AB  - BACKGROUND: Metastatic spinal tumors are common and major causes of pathological
      spinal fractures that result in severe pain, weakness, and progressive
      neurological deficits. This study aims to evaluate the efficacy of percutaneous
      vertebroplasty (PVP) in pain-relief in patients with spinal fractures due to
      metastatic spinal tumors. METHODS: We evaluated 25 documented cases of metastatic
      spinal tumors with pathologic vertebral fractures who were suffering from severe
      pain and underwent vertebroplasty. Degree of pain was measured by visual analog
      scale (VAS). The symptoms were evaluated 24 hours and 2 months after
      vertebroplasty regarding the degree of pain relief.Complications such as leakage,
      embolism and infection were assessed. RESULTS: MeanVAS score was 8.23 before
      therapy in the patients that was reduced to 2.12 and 1 in the patients 24 hours
      and 2 months after vertebroplasty, respectively. The most common complication was
      cement leakage (44%) and there was no embolism or infection. Data was analyzed by
      SPSS version 18 software through ANOVA test with Greenhouse-Geisser correction
      and P-value of 0.00 was obtained in the patients 24 hours and 1 month after
      surgery. CONCLUSION: Considering significant decrease in the mean pain severity
      degree after the treatment, veretebroplasty seems to be significantly effective
      in pain relief in metastatic spinal tumors.

PMID- 23115715
TI  - Burden and typing of rotavirus group a in children with acute gastroenteritis in
      shiraz, southern iran.
AB  - BACKGROUND: Human Rotavirus is a significant cause of severe gastroenteritis in
      infants and young children worldwide. In recent years, Rotavirus genotyping by RT
      PCR has provided valuable information about the diversity of Rotaviruses
      circulating worldwide. The purpose of the present study is to monitor the
      prevalence of the different G types of Rotaviruses circulating in Shiraz,
      Southern Iran and detect any uncommon or novel types. METHODS: During the period
      from December 2007 to November 2008, a total of 138 stool samples were collected
      from children less than 5 years old who were hospitalized for acute
      gastroenteritis. Rotavirus-associated diarrhea was investigated in fecal
      specimens with enzyme immunoassays (EIA). Rotavirus-positive specimens were typed
      by the Nested RT-PCR and by using different types of specific primers. RESULTS:
      Out of the 138 collected samples, 34.78% (48 cases) tested positive for
      Rotavirus. The frequency of G1, G2 and G4 types was 6.25%, 2.08% and 27.08%,
      respectively. Mixed and non-typeable infections were detected in 33.34% and
      31.25% of hospitalized children with acute diarrhea, respectively. This is the
      first time mixed Rotavirus infections with G1/G3 have been reported in Iran.
      CONCLUSION: The high frequency of Rotavirus detection indicates the severity and
      the burden of Rotavirus disease may be able to reduce through the implementation
      of an effective vaccine and continual surveillance for the detection of Rotavirus
      genotypes circulating in other regions of Iran. Regarding to the noticeable
      frequency of non-typeable and mixed infections, it is suggested to use the other
      specific primers and further studies to detection of other novel and unusual
      types.

PMID- 23115716
TI  - The diagnostic power of cervico-vaginal fluid prolactin in the diagnosis of
      premature rupture of membranes.
AB  - BACKGROUND: Premature rupture of membranes (PROM) is one of the most common
      complications of pregnancy that has a major impact on pregnancy outcomes. A
      diagnostic tool that is non-invasive, specific and quick is needed to predict
      PROM. The purpose of this study was to evaluate the diagnostic power of the
      vaginal washing fluid prolactin for the diagnosis of premature rupture of
      membranes and to determine cut-off values. METHODS: A total of 114 pregnant women
      were recruited in this diagnostic trial. The PROM group consisted of 54 pregnant
      women between 20 and 41 weeks of gestation with diagnosis of confirmed PROM
      [amniotic fluid pooling (+) and Nitrazine paper test (+) and fernt test (+)]. The
      control group consisted of 60 pregnant women between 20 and 41 weeks of gestation
      without any complaint or complication. All patients underwent speculum
      examination for amniotic fluid pooling, nitrazine paper test, fern test, vaginal
      washing fluid prolactin sampling. RESULTS: Vaginal fluid concentrations of
      prolactin was significantly different between the two groups (P < 0.001). The
      sensitivity, specificity, positive and negative predictive values and accuracy
      were 87.03%, 75.0%, 75.80%, 86.53% and 83.33% in detecting PROM by evaluation of
      vaginal fluid prolactin concentration with a cut-off value of 9.50 uIU/ml,
      respectively. CONCLUSIONS: The prolactin levels in the washing fluid of the
      posterior vaginal fornix in our experience is reliable and non-invasive
      diagnostic tests of PROM.

PMID- 23115717
TI  - Respiratory disorders associated with heavy inhalation exposure to dolomite dust.
AB  - BACKGROUND: Although dolomite is classified as a relatively non-toxic, nuisance
      dust, little information exists as to its potential to produce respiratory
      disorders following occupational exposure. The purpose of this study was,
      therefore, to evaluate the possible effects, if any, of heavy inhalation exposure
      to this chemical on the prevalence of respiratory symptoms, functional
      impairments and radiographic abnormalities of the lungs. METHODS: The study
      population consisted of a group of 39 exposed subjects engaged in digging and
      excavating activities that were in operation for building a local dam, as well as
      40 healthy non-exposed employees that served as the referent group. Subjects were
      interviewed and respiratory symptoms questionnaires, as suggested by the American
      Thoracic Society (ATS), were completed for them. Thereafter, they underwent chest
      X-ray and lung function tests. Additionally, using routine gravimetric
      techniques, personal dust monitoring for airborne inhalable and respirable dust
      was carried out at different dusty work sites. Finally to determine the chemical
      composition of the dust, it was analyzed by X-ray fluorescence (XRF) technique.
      RESULTS: XRF revealed that the major component (50.52%) of the dust was calcium
      magnesium carbonate, dolomite. Additionally, levels of exposure to inhalable and
      respirable dust were estimated to be 51.7+/-24.31 and 23.0+/-18.11mg/m3,
      respectively. Statistical analysis of the data showed that symptoms such as
      regular cough, phlegm, wheezing, productive cough and shortness of breath were
      significantly (p<0.05) more prevalent among exposed workers. Similarly, the ratio
      of FEV1/FVC in exposed subjects was significantly different from that of non
      exposed individuals. In contrast, no significant abnormalities were observed in
      the chest radiographs of both groups. CONCLUSIONS: In conclusion, while these
      data cast doubt on the notion that dolomite is a harmless chemical, they provide
      evidence in favour of the proposition that exposure to high atmospheric
      concentrations of this compound is likely to be associated with respiratory
      symptoms.

PMID- 23115718
TI  - Ultrastructural and morphometrical changes of mice ovaries following
      experimentally induced copper poisoning.
AB  - BACKGROUND: Copper (Cu) is an essential trace element involved in normal
      reproduction but its overexposure may produce some detrimental effects. The aim
      of this study was to investigate the effects of copper sulfate poisoning on
      morphometery of mice ovarian structures and probable intracellular changes.
      METHODS: Thirty mature female mice were randomly allocated to control and two
      treatment groups. In treatment groups, two different doses of copper sulfate
      including 100 mg/kg and 200 mg/kg in 0.2 cc were applied once a day for 35
      consecutive days by gavage. Control animals received normal saline using the same
      volume and similar method. Animals from each experimental group were sacrificed
      14 and 35 days after the beginning of drug administration and the left ovaries
      were removed for stereological evaluations by light microscopy and right ovaries
      were obtained for preparing electron microscopic sections. RESULTS: The
      morphometrical results showed that only the number of antral follicles was
      decreased by 100 mg/kg copper sulfate on day 14 compared to the control group
      (P=0.043). Hence, higher copper dose or longer consumption period significantly
      reduced different classes of follicles and corpora lutea. With 100 mg/kg copper
      sulfate some mild ultrastructural cell damages such as decrease of zona pellucida
      thickness, limited vacuolated areas and nuclear envelop dilation were seen on day
      14. Higher or longer Cu administration produced more detrimental effects
      including more vacuolated areas, presence of secondary lysosomes, irregularity in
      cell shape and segmented nuclei with condensed and marginated chromatin and more
      enlarged and damaged mitochondria. CONCLUSION: New evidences of early as well as
      late intracellular damages of copper has been presented by accurate stereological
      and ultrastructural methods. Antral follicles was the most susceptible cells with
      the lower and shorter copper consumption and long term or higher dose of copper
      affected the whole of ovarian structures.

PMID- 23115719
TI  - Lidocaine Cyclodextrin complex Ophthalmic Drop, a New Topical Anesthetic Choice.
AB  - BACKGROUND: Topical anesthesia is a safe and cost-effective method considered as
      the first-choice in many procedures. Due to the physiological characteristics of
      eye, most of the local anesthetics cannot efficiently penetrate through the
      conjunctiva deep to tenon. The aim of this pilot study was to find a new form of
      lidocaine to give a sufficient level of anesthesia. METHODS: Lidocaine
      Cyclodextrin complex ophthalmic drop was produced and its pharmacological
      properties were studied [tested] in standard temperature and pressure. 30
      patients (18 males, 12 females) with the mean age of 30.68+/-8.02 years enrolled
      in this clinical trial. All the patients were fully informed and signed the
      ethics committee consent forms. The patients were given tetracaine drop as the
      anesthetic: 3 drops separated 2 minute apart 10 min before the intervention. If
      we achieved a sufficient level of anesthesia, the procedure was done after. If
      the patient could not tolerate the procedure, the method was changed to lidocaine
      drop (administered after wash-out period like the first drop).The last option was
      conventional injection method if the patient could not tolerate the procedure
      with the second method either.We used this type of anesthesia for conventional
      procedures such as forced duction test, symblepharon, pterygium, and disport
      injection into extra-ocular muscles. All the procedures were done by one surgeon
      in a university hospital. We used a 0 to 10 visual analogue scale for pain and
      two 0 to 4 patient and physician satisfaction scales designed for this study.
      RESULTS: The mean pain score was 7.53+/-0.90 in group 1 and 3.03+/-1.83 in group
      2 (P=0.00). Patient and surgeon satisfaction in group 1 were 1.33+/-0.48 and
      1.40+/-0.56 respectively; while 3.23+/-1.00 and 3.56+/-0.77 for group 2 (P=0.00).
      Tetracaine drop could not induce sufficient anesthesia for none of the patients.
      Cyclodextrin based lidocaine drop was successful except For two patients for whom
      we changed the anesthesia to Sub-conjunctival injection method. CONCLUSION: Our
      newly manufactured cyclodextrin based lidocaine eye drop could successfully
      induce sufficient anesthesia for 28 of 30 patients. Further studies with larger
      sample sizes are now being designed to find more clinical evidence about this
      method.

PMID- 23115720
TI  - Spontaneous resolution of paraparesis because of acute spontaneous thoracolumbar
      epidural hematoma.
AB  - BACKGROUND: Symptomatic spontaneous spinal epidural hematoma(SSEH) is an uncommon
      cause of cord compression that commonly is considered an indication for emergent
      surgical decompression. We aimed to investigate a patient with a SSEH that
      completely resolved clinically and radiographically, without surgical treatment.
      The patient presented three days after the sudden onset of back pain, numbness,
      and weakness. Magnetic Resonance Imaging (MRI) revealed a posterior thoracolumbar
      epidural hematoma extending from the level of T10 to L2 with significant cord
      compression. Decompression was recommended but he refused surgery and was managed
      conservatively. One month later weakness totally recovered and hematoma was
      absent on MRI.

PMID- 23115721
TI  - Cutis marmorata telangiectatica congenita in a preterm newborn - Case report and
      literature review.
AB  - BACKGROUND: Cutis marmorata telangiectatica congenita (CMTC) is a sporadic
      congenital skin vascular abnormality. Significant number of patients has other
      congenital anomalies. CASE REPORT: We report a case of a preterm male newborn
      with cutis marmorata pattern presented on the skin of the face, right side of
      front of the trunk, whole back, glutei and both legs. Besides, microretrognatia
      and asymmetric, bad-formed, low-set ears were notable. Ophthalmologic findings
      showed visual impairment and pale optic nerve papilla. Monitoring of child showed
      mental underdevelopment and motor retardation. CONCLUSION: CMTC is a rare finding
      with good prognosis of skin malformations, with an obligation of dermatologist
      and paediatrician to investigate other associated congenital anomalies.

PMID- 23115722
TI  - Late development of pancreatitis following gunshot trauma, a case report.
AB  - BACKGROUND: Gunshot trauma to the pancreatic duct mainly have been published from
      wartime experiences, but bullet injury in these cases has lead to pancreatic duct
      disruption, not obstruction. We report a case of chronic pancreatitis which is
      presented 27 years following pancreatic duct obstruction due to bullet injury
      during wartime, which successfully treated. He was a 45-year-old man came with
      chronic epigastric abdominal pain. Physical examination was suggestive of
      pancreatitis and laboratory data confirmed the diagnosis. Imaging studies
      revealed a metallic object in main pancreatic duct. He carefully treated with
      pancreatic head resection and pancreaticojejunal anastomosis.

PMID- 23115723
TI  - Decreased serum level of soluble-leptin-receptor in patients with systemic lupus
      erythematosus.
AB  - BACKGROUND: There is some evidence suggesting that leptin and its negative
      regulator, soluble-leptinreceptor (SLR) may be able to influence inflammatory and
      autoimmune processes. METHODS: In this study, several variables including socio
      demographics, health-related habits, depression score, serum molecules and blood
      parameters besides the SLR level were evaluated in patients with SLE (SLE
      patients) and healthy controls. RESULTS: The patients had significantly lower SLR
      level and higher depression score than the controls and both of these variables
      have a significant association with the occurrence of disease in logistic
      regression model. Moreover, the results of Pearson correlation analysis showed
      that patients' SLR level was negatively correlated with their weights and BDI
      scores. CONCLUSION: For the first time, this study indicated a lower level of SLR
      in SLE-patients and suggested that lower concentrations of SLR in these patients
      may be implicated in the pathogenesis of SLE.

PMID- 23115724
TI  - Rapid Detection of Escherichia coli O157: H7 by Fluorescent Amplification-Based
      Specific Hybridization (FLASH) PCR.
AB  - BACKGROUND: Escherichia coli O157:H7 is an enteric pathogen which can be
      frequently found asymptomatically in ruminant mammals, but can cause diseases
      from mild diarrhea to hemolytic uremic syndrome in humans. METHODS: We developed
      fluorescent amplification-based specific hybridization (FLASH-PCR) assay to
      detect the Stx-encoding gene Stx-1 of E. coli O157:H7. RESULT: PCR product of 336
      bp was successfully amplified in a FLASH-PCR. CONCLUSION: As rapid detection and
      confirmation of the presence of E. coli O157:H7 are of importance for the
      medical, food, and water industries, FLASH-PCR is one of selective methods for
      detection of E. coli O157:H7.

PMID- 23115725
TI  - Double J-related hemoperitoneum in a living-related renal transplantation
      recipien.

PMID- 23115726
TI  - Highly Cytokinergic IgE Antibodies and Autoimmune Mechanisms.

PMID- 23115728
TI  - Treatment of chronic spontaneous urticaria.
AB  - Chronic spontaneous urticaria is defined as persistent symptoms of urticaria for
      6 weeks or more. It is associated with autoimmunity in approximately 45 percent
      of patients. Therapy is often difficult however the initial approach should
      employ high-dose non-sedating antihistamines; 4-6 tablets/day may be necessary.
      It has been shown that the response to 4 tablets/day exceeds 3, and exceeds 2,
      which exceeds 1. However the dose that corresponds to the maximal dose of first
      generation antihistamines (hydroxyzine, diphenhydramine) used previously, is
      6/day. Yet over half the patients are refractory to antihistamines and other
      agents should be tried next. Whereas current guidelines (published) often add
      leukotriene antagonists and/or H(2) receptor antogonists next, these are of
      little utility. Likewise drugs effective for urticarial vasculitis (colchicine,
      dapsone, sulfasalazine, hydroxychloroquine) are effective in a small percentage
      of patients and no study suggests that the response rate of any of them exceeds
      the 30% placebo responses seen in most double-blind, placebo controlled studies.
      The drugs that are effective for antihistamine-resistant chronic spontaneous
      urticaria are corticosteroids, cyclosporine, and Omalizumab. Use of steroids is
      limited by toxicity. If used at all, a dose of no more than 10 mg/day should be
      employed with a weekly reduction of 1 mg. The response rates to cyclosporine and
      Omalizumab are each close to 75%. Cyclosporine can be used effectively if care is
      taken to monitor blood pressure, urine protein, blood urea nitrogen, and
      creatinine, every 6 weeks. Omalizumab has the best profile in terms of
      efficacy/toxicity and, once approved by federal agencies for use in chronic
      spontaneous urticaria, a dramatic change in the treatment paradigm, whether
      associated with autoimmunity or not, is predicted. A phase 3 trial is currently
      in place. Refractoriness to both Omalizumab and cyclosporine is expected to be
      less than 5 percent of patients. Other agents, can then be tried.

PMID- 23115727
TI  - House dust mite allergy in Korea: the most important inhalant allergen in current
      and future.
AB  - The house-dust mite (HDM), commonly found in human dwellings, is an important
      source of inhalant and contact allergens. In this report, the importance of HDM
      allergy in Korea and the characteristics of allergens from dust mite are reviewed
      with an emphasis on investigations performed in Korea. In Korea, Dermatophagoides
      farinae is the dominant species of HDM, followed by D. pteronyssinus. Tyrophagus
      putrescentiae is also found in Korea, but its role in respiratory allergic
      disease in Korea is controversial. The relatively low densities of mite
      populations and concentrations of mite major allergens in dust samples from
      Korean homes, compared to westernized countries, are thought to reflect not only
      different climatic conditions, but also cultural differences, such as the use of
      'ondol' under-floor heating systems in Korean houses. HDM are found in more than
      90% of Korean houses, and the level of exposure to HDM is clinically significant.
      About 40%-60% of Korean patients suffering from respiratory allergies, and more
      than 40% of patients suffering from atopic dermatitis, are sensitized to HDM.
      Mite allergens can be summarized according to their inherent auto-adjuvant
      activities and/or their binding affinities to the adjuvant-like substances:
      proteolytic enzymes, lipid binding proteins, chitin binding proteins, and
      allergens not associated with adjuvant-like activity. In general, allergens with
      a strong adjuvant-like activity or adjuvant-binding activity elicit potent IgE
      reactivity. In Korea, Der f 2 is the most potent allergen, followed by Der f 1.
      Immune responses are modulated by the properties of the allergen itself and by
      the adjuvant-like substances that are concomitantly administered with the
      antigens. Characterization of allergenic molecules and elucidation of mechanisms
      by which adjuvant-like molecules modulate allergic reactions, not only in Korea
      but also worldwide, will provide valuable information on allergic diseases, and
      are necessary for the development of diagnostic tools and therapeutic strategies.

PMID- 23115729
TI  - Most Highly Cytokinergic IgEs Have Polyreactivity to Autoantigens.
AB  - PURPOSE: Monomeric IgE molecules, when bound to the high-affinity receptor,
      exhibit a vast heterogeneity in their ability to induce survival promotion and
      cytokine production in mast cells. At one end of this spectrum, highly
      cytokinergic (HC) IgEs can induce potent survival promotion, degranulation,
      cytokine production, migration, etc., whereas at the other end, poorly
      cytokinergic (PC) IgEs can do so inefficiently. In this study, we investigated
      whether IgEs recognize autoantigens and whether IgEs' binding of autoantigens
      correlates with difference s in HC versus PC properties. METHODS: Enzyme-linked
      immunosorbent assays were performed to test whether IgEs bind antigens. Histamine
      releasing factor in human sera was quantified by western blotting. Cultured mast
      cells derived from human cord blood were used to test the effects of human sera
      on cytokine production. RESULTS: Most (7/8) of mouse monoclonal HC IgEs exhibited
      polyreactivity to double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), beta
      galactosidase, thyroglobulin and/or histamine-releasing factor. By contrast,
      mouse PC IgEs failed to react with these antigens. A human monoclonal HC IgE also
      showed polyreactivity to histamine-releasing factor, dsDNA and ssDNA.
      Interestingly, sera from atopic dermatitis patients showed increased reactivity
      to ssDNA and beta-galactosidase and increased levels of histamine-releasing
      factor. Some atopic dermatitis patients, but not healthy individuals, had
      substantial serum levels of HRF-reactive IgE. Sera from atopic dermatitis
      patients with high titers of DNA-reactive IgE could induce several fold more IL-8
      secretion in human mast cells than sera from healthy individuals. CONCLUSIONS:
      The results show that most HC, but not PC, IgEs exhibit polyreactivity to
      autoantigens, supporting the autoimmune mechanism in the pathogenesis of atopic
      dermatitis.

PMID- 23115730
TI  - Bronchial Hyperresponsiveness to Methacholine and AMP in Children With Atopic
      Asthma.
AB  - PURPOSE: Bronchial hyperresponsiveness (BHR) is typically measured by bronchial
      challenge tests that employ direct stimulation by methacholine or indirect
      stimulation by adenosine 5'-monophosphate (AMP). Some studies have shown that the
      AMP challenge test provides a better reflection of airway inflammation, but few
      studies have examined the relationship between the AMP and methacholine challenge
      tests in children with asthma. We investigated the relationship between AMP and
      methacholine testing in children and adolescents with atopic asthma. METHODS: The
      medical records of 130 children with atopic asthma (mean age, 10.63 years) were
      reviewed retrospectively. Methacholine and AMP test results, spirometry, skin
      prick test results, and blood tests for inflammatory markers (total IgE,
      eosinophils [total count, percent of white blood cells]) were analyzed. RESULTS:
      The concentration of AMP that induces a 20% decline in forced expiratory volume
      in 1 second [FEV1] (PC20) of methacholine correlated with the PC20 of AMP
      (r(2)=0.189, P<0.001). No significant differences were observed in the levels of
      inflammatory markers (total eosinophil count, eosinophil percentage, and total
      IgE) between groups that were positive and negative for BHR to methacholine.
      However, significant differences in inflammatory markers were observed in groups
      that were positive and negative for BHR to AMP (log total eosinophil count,
      P=0.023; log total IgE, P=0.020, eosinophil percentage, P<0.001). In contrast,
      body mass index (BMI) was significantly different in the methacholine positive
      and negative groups (P=0.027), but not in the AMP positive and negative groups
      (P=0.62). The PC20 of methacholine correlated with FEV1, FEV1/forced vital
      capacity (FVC), and maximum mid-expiratory flow (MMEF) (P=0.001, 0.011, 0.001,
      respectively), and the PC20 of AMP correlated with FEV1, FEV1/FVC, and MMEF
      (P=0.008, 0.046, 0.001, respectively). CONCLUSIONS: Our results suggest that the
      AMP and methacholine challenge test results correlated well with respect to
      determining BHR. The BHR to AMP more likely implicated airway inflammation in
      children with atopic asthma. In contrast, the BHR to methacholine was related to
      BMI.

PMID- 23115731
TI  - Standardization of house dust mite extracts in Korea.
AB  - PURPOSE: House dust mites are the most important cause of respiratory allergy in
      Korea. Standardization of allergen extracts is essential for improving
      diagnostics and immunotherapeutics. This study was undertaken to evaluate the
      allergenicity of standardized house dust mite allergen extracts from Korean house
      dust mite isolates. METHODS: Allergen extracts were prepared from cultured Korean
      house dust mites (Dermatophagoides farinae and D. pteronyssinus). Allergenic
      activities of Korean house dust mite extracts were compared to standardized
      extracts from a company in the United States whose allergen concentrations were
      expressed as Allergy Units (AUs). Specifically, we compared group 1 and 2 major
      allergens using two-site enzyme-linked immunosorbent assay (ELISA) kits and an in
      vivo intradermal test. RESULTS: Major allergen concentrations were 17.0 ug/mg
      (5.0 ug/mg of Der f 1 and 12.0 ug/mg of Der f 2) for a D. farinae extract and
      24.0 ug/mg (11.6 ug/mg of Der p 1 and 12.4 ug/mg of Der p 2) for a D.
      pteronyssinus extract. Using chloramphenicol (CAP) inhibition assays, AUs were
      12.5 AU/ug for a D. farinae extract and 12.8 AU/ug for a D. pteronyssinus
      extract. Allergenic activities were 3- to 4-fold stronger when assessed by
      intradermal skin tests for in vivo standardization. CONCLUSIONS: Allergen
      extracts were prepared from Korean house dust mites and the allergenicities of
      the extracts were estimated using AU measurements. House dust mite extracts
      prepared in this study could be utilized as a reference material, which will be
      useful for the development of diagnostic and immunotherapeutic reagents in Korea.

PMID- 23115732
TI  - Elevated Serum Levels of IL-21 in Kawasaki Disease.
AB  - PURPOSE: The serum level of immunoglobulin (Ig)E has been reported to be elevated
      in patients with Kawasaki disease (KD). We investigated whether interleukin (IL)
      21, rather than IL-4, could be related to elevated serum levels of IgE in KD.
      METHODS: Sera from 48 patients with KD and 12 controls with high fever were
      collected to determine the level of IgE using an immunoassay system and the
      levels of IL-4 and IL-21 were determined using enzyme-linked immunosorbent assay
      kits. RESULTS: The median IL-21 level of KD patients was significantly elevated,
      at 499.5 pg/mL (range: <62.5-1,544 pg/mL), whereas that of controls was <62.5
      pg/mL (<62.5-825 pg/mL; P<0.001). The median IL-4 level of KD patients was not
      elevated (4.0 pg/mL; 2.1-7.6 pg/mL). The median level of total IgE in KD patients
      was 58.0 IU/mL (5-1,109 IU/mL). No statistically significant correlation was
      found between IL-21 and total IgE levels (Spearman's R=0.2; P=0.19). CONCLUSIONS:
      Patients with KD have elevated levels of IL-21 in the serum. IL-21 may play a
      role in the pathogenesis of KD.

PMID- 23115733
TI  - Effects of omalizumab treatment in patients with refractory chronic urticaria.
AB  - PURPOSE: Chronic urticaria (CU) is a common and debilitating disease, and the
      need for effective treatment has increased. Omalizumab may be an alternative
      regimen in patients with CU who do not respond to conventional treatments. The
      aim of this study is to investigate the efficacy and to observe the clinical
      results of omlizumab in patients with refractory CU. METHODS: We conducted a
      retrospective analysis of 26 patients with refractory CU who were treated with
      omalizumab. Omalizumab was administered every 2 or 4 weeks, depending on body
      weight and the total serum IgE level, for 24 weeks. RESULTS: Fourteen patients
      (53.8%) achieved remission after the treatment; they had a significantly higher
      prevalence of personal (P=0.033) and family history of allergic diseases
      (P=0.002) than those who did not achieve remission. During omalizumab treatment,
      the urticaria activity score declined significantly (12.11+/-1.97 to 2.7+/-4.23;
      P=0.001) and the CU-quality of life score improved significantly (34.65+/-13.58
      to 60.88+/-11.11; P=0.004). There were significant decreases in the use of
      systemic steroids (42.3%-11.5%; P=0.027) and immunomodulators (65.4%-19.2%;
      P=0.002). The dose of antihistamines required to control CU also decreased
      significantly (215.66+/-70.06 to 60.85+/-70.53 mg/week of loratadine equivalents;
      P<0.001). No serious adverse event was noted. CONCLUSIONS: These findings suggest
      that omalizumab can be an effective and safe treatment in patients with
      refractory CU.

PMID- 23115734
TI  - ABCC2 Haplotype is Associated With Antituberculosis Drug-Induced Maculopapular
      Eruption.
AB  - Genetic variants in ATP-binding cassette (ABC) transporter genes are associated
      with increased susceptibility to adverse drug reactions. We hypothesized that
      genetic variant ABC transporters (ABCB1 and ABCC2) may be candidate markers for
      predicting maculopapular eruption (MPE) induced by antituberculosis therapy. We
      compared the genotype distributions of single nucleotide polymorphisms and
      haplotypes in the ABCB1 and ABCC2 genes between 62 antituberculosis drug (ATD)
      induced MPE cases and 159 ATD-tolerant controls using multivariate logistic
      regression analysis. There was no significant association between genetic
      polymorphisms in ABCB1 and ATD-induced MPE (P>0.05). Among seven selected SNPs of
      ABCC2, IVS3-49C>T in intron and I1324I were associated with ATD-induced MPE
      (P=0.029 and 0.036, respectively). In an analysis of the ABCC2 haplotypes (ht; 
      1549G>A_-24C>T_IVS3-49C>T_V417I), ht1[G-C-C-G] was significantly associated with
      ATD-induced MPE (P=0.032, OR=0.35, 95% CI: 0.16-0.95). No significant association
      between the other haplotypes and ATD-induced MPE was observed. An ABCC2 haplotype
      is associated with the presence of ATD-induced MPE in patients with tuberculosis
      and may be a genetic risk factor for the development of MPE induced by ATD.

PMID- 23115735
TI  - Immunologic evaluation of ofloxacin hypersensitivity.
AB  - Quinolone hypersensitivity, most of which is immediate type, is rare but has
      increased in recent years. The pathogenic mechanisms underlying immediate
      reactions are not defined clearly. This study was aimed to observe the clinical
      characteristics of immediate hypersensitivity to ofloxacin and to investigate the
      pathogenic mechanism with detection of serum specific IgE to ofloxacin using an
      enzyme-linked immunoasorbent assay (ELISA). We recruited 5 patients with
      immediate hypersensitivity reactions to ofloxacin (group I), and as control
      groups, 5 subjects with ciprofloxacin hypersensitivity (group II) and 20 healthy
      subjects with no history of drug allergy. Serum specific-IgE to ofloxacin-human
      serum albumin (HSA) conjugate was detectable in four group I subjects (80%) and
      three group II subjects (60%). The ELISA inhibition test showed significant
      inhibition with both ofloxacin-HSA conjugate and free ofloxacin in a dose
      dependent manner. As to ciprofloxacin, significant inhibition was noted upon
      addition of free ciprofloxacin in one subject, while minimal inhibition was noted
      in the other. We confirmed that an IgE-mediated response is a major pathogenic
      mechanism of ofloxacin hypersensitivity. Cross reactivity between ofloxacin and
      ciprofloxacin was noted with individual difference.

PMID- 23115736
TI  - Special editorial.

PMID- 23115737
TI  - Application of stereo-imaging technology to medical field.
AB  - OBJECTIVES: There has been continuous development in the area of stereoscopic
      medical imaging devices, and many stereoscopic imaging devices have been realized
      and applied in the medical field. In this article, we review past and current
      trends pertaining to the application stereo-imaging technologies in the medical
      field. METHODS: We describe the basic principles of stereo vision and visual
      issues related to it, including visual discomfort, binocular disparities,
      vergence-accommodation mismatch, and visual fatigue. We also present a brief
      history of medical applications of stereo-imaging techniques, examples of
      recently developed stereoscopic medical devices, and patent application trends as
      they pertain to stereo-imaging medical devices. RESULTS: Three-dimensional (3D)
      stereo-imaging technology can provide more realistic depth perception to the
      viewer than conventional two-dimensional imaging technology. Therefore, it allows
      for a more accurate understanding and analysis of the morphology of an object.
      Based on these advantages, the significance of stereoscopic imaging in the
      medical field increases in accordance with the increase in the number of
      laparoscopic surgeries, and stereo-imaging technology plays a key role in the
      diagnoses of the detailed morphologies of small biological specimens.
      CONCLUSIONS: The application of 3D stereo-imaging technology to the medical field
      will help improve surgical accuracy, reduce operation times, and enhance patient
      safety. Therefore, it is important to develop more enhanced stereoscopic medical
      devices.

PMID- 23115739
TI  - Development of clinical contents model markup language for electronic health
      records.
AB  - OBJECTIVES: To develop dedicated markup language for clinical contents models
      (CCM) to facilitate the active use of CCM in electronic health record systems.
      METHODS: Based on analysis of the structure and characteristics of CCM in the
      clinical domain, we designed extensible markup language (XML) based CCM markup
      language (CCML) schema manually. RESULTS: CCML faithfully reflects CCM in both
      the syntactic and semantic aspects. As this language is based on XML, it can be
      expressed and processed in computer systems and can be used in a technology
      neutral way. CONCLUSIONS: CCML HAS THE FOLLOWING STRENGTHS: it is machine
      readable and highly human-readable, it does not require a dedicated parser, and
      it can be applied for existing electronic health record systems.

PMID- 23115738
TI  - Clinical care improvement with use of health information technology focusing on
      evidence based medicine.
AB  - OBJECTIVES: Healthcare institutions need timely patient information from various
      sources at the point-of-care. Evidence-based medicine (EBM) is a tool for proper
      and efficient incorporation of the results of research in decision-making.
      Characteristics of medical treatment processes and practical experience
      concerning the effect of EBM in the clinical process are surveyed. METHODS: A
      cross sectional survey conducted in Tehran hospitals in February-March 2012 among
      51 clinical residents. The respondents were asked to apply EBM in clinical
      decision-making to answer questions about the effect of EBM in the clinical
      process. A valid and reliable questionnaire was used in this study. RESULTS: EBM
      provides a framework for problem solving and improvement of processes. Most
      residents (76%) agreed that EBM could improve clinical decision making. Eighty
      one percent of the respondents believed that EBM resulted in quick updating of
      knowledge. They believed that EBM was more useful for diagnosis than for
      treatment. There was a significant association between out-patients and in
      patients in using electronic EBM resources. CONCLUSIONS: Research findings were
      useful in clinical practice and decision making. The computerized guidelines are
      important tools for improving clinical process quality. When learning how to use
      IT, methods of search and evaluation of evidence for diagnosis, treatment and
      medical education are necessary. Purposeful use of IT in clinical processes
      reduces workload and improves decision-making.

PMID- 23115740
TI  - Data mining application in customer relationship management for hospital
      inpatients.
AB  - OBJECTIVES: This study aims to discover patients loyal to a hospital and model
      their medical service usage patterns. Consequently, this study proposes a data
      mining application in customer relationship management (CRM) for hospital
      inpatients. METHODS: A recency, frequency, monetary (RFM) model has been applied
      toward 14,072 patients discharged from a university hospital. Cluster analysis
      was conducted to segment customers, and it modeled the patterns of the loyal
      customers' medical services usage via a decision tree. RESULTS: Patients were
      divided into two groups according to the variables of the RFM model and the group
      which had significantly high frequency of medical use and expenses was defined as
      loyal customers, a target market. As a result of the decision tree, the
      predictable factors of the loyal clients were; length of stay, certainty of
      selectable treatment, surgery, number of accompanying treatments, kind of patient
      room, and department from which they were discharged. Particularly, this research
      showed that when a patient within the internal medicine department who did not
      have surgery stayed for more than 13.5 days, their probability of being a
      classified as a loyal customer was 70.0%. CONCLUSIONS: To discover a hospital's
      loyal patients and model their medical usage patterns, the application of data
      mining has been suggested. This paper suggests practical use of combining
      segmentation, targeting, positioning (STP) strategy and the RFM model with data
      mining in CRM.

PMID- 23115741
TI  - Comparison of Knowledge Levels Required for SNOMED CT Coding of Diagnosis and
      Operation Names in Clinical Records.
AB  - OBJECTIVES: Coding Systematized Nomenclature of Medicine, Clinical Terms (SNOMED
      CT) with complex and polysemy clinical terms may ask coder to have a high level
      of knowledge of clinical domains, but with simpler clinical terms, coding may
      require only simpler knowledge. However, there are few studies quantitatively
      showing the relation between domain knowledge and coding ability. So, we tried to
      show the relationship between those two areas. METHODS: We extracted diagnosis
      and operation names from electronic medical records of a university hospital for
      500 ophthalmology and 500 neurosurgery patients. The coding process involved one
      ophthalmologist, one neurosurgeon, and one medical record technician who had no
      experience of SNOMED coding, without limitation to accessing of data for coding.
      The coding results and domain knowledge were compared. RESULTS: 705 and 576
      diagnoses, and 500 and 629 operation names from ophthalmology and neurosurgery,
      were enrolled, respectively. The physicians showed higher performance in coding
      than in MRT for all domains; all specialist physicians showed the highest
      performance in domains of their own departments. All three coders showed
      statistically better coding rates in diagnosis than in operation names (p <
      0.001). CONCLUSIONS: Performance of SNOMED coding with clinical terms is strongly
      related to the knowledge level of the domain and the complexity of the clinical
      terms. Physicians who generate clinical data can be the best potential candidates
      as excellent coders from the aspect of coding performance.

PMID- 23115742
TI  - Computer and internet interventions for loneliness and depression in older
      adults: a meta-analysis.
AB  - OBJECTIVES: This study conducted a meta-analysis to examine the effectiveness of
      computer and Internet training interventions intended to reduce loneliness and
      depression in older adults. METHODS: Searches were performed to retrieve studies
      that had been published in peer-reviewed journals from January 2001 to July 2012
      and written in English or Korean from PubMed, CINAHL, Scopus, the Cochrane
      Library, PsycINFO, KoreaMed, KMbase, KISS, MEDLIS, and RISS. We used combinations
      of the keywords for population, intervention, and psychosocial problems. A meta
      analysis was employed to summarize the findings of studies on computer and
      Internet interventions for older adults. An overall mean weighted effect size for
      each outcome was calculated, and Q statistics were used to test the heterogeneity
      of variance in the effect sizes of the selected studies. RESULTS: As the Q
      statistics revealed heterogeneity, random effects models were chosen for the meta
      analysis. The overall mean weighted effect size for loneliness from five studies
      was statistically significant for decreased loneliness (Z = 2.085, p = 0.037).
      However, the overall mean weighted effect size for depression from five studies
      was not statistically significant (Z = 1.528, p = 0.126). CONCLUSIONS: These
      results suggest that computer and Internet programs were effective in managing
      loneliness among older adults. Therefore, further computer-mediated social
      support should be considered to help manage loneliness in this population.

PMID- 23115743
TI  - Effect of Integrated Personalized Health Care System on Middle-Aged and Elderly
      Women's Health.
AB  - OBJECTIVES: Body weight, body mass index (BMI), body fat, and blood pressure are
      important indicators of a person's health. In this experimental study, we
      evaluated the effectiveness of an integrated personalized health care system,
      Health Improvement and Management System (HIMS)-everyday, which instantly
      provides subjects with biofeedback on their measured body weight, BMI, body fat
      and blood pressure using a database that stores subjects-customized information.
      METHODS: The subjects of this study used the system once or twice a week for 8
      weeks. We analyzed the changes in their body weight, BMI, body fat, and blood
      pressure according to their respective usage of the system, and analyzed the
      changes in their perceived health status and health promoting behavior
      accordingly. RESULTS: Subjects' body weight, BMI, and blood pressure decreased
      significantly with respect to their individual usage of the system. Subjects who
      used the system more frequently showed significant improvement in their body
      weight, BMI, and body fat. However, subjects' perceived health status and health
      promoting behavior did not improve significantly. CONCLUSIONS: The study showed
      that the biofeedback-based personalized health care system was effective in
      controlling middle-aged and elderly women' body weight, BMI, body fat, and blood
      pressure.

PMID- 23115744
TI  - Performance analysis of hospital information system of the national health
      insurance corporation ilsan hospital.
AB  - OBJECTIVES: This study evaluated the qualitative and quantitative performances of
      the newly developed information system which was implemented on November 4, 2011
      at the National Health Insurance Corporation Ilsan Hospital. METHODS:
      Registration waiting time and changes in the satisfaction scores for the key
      performance indicators (KPI) before and after the introduction of the system were
      compared; and the economic effects of the system were analyzed by using the
      information economics approach. RESULTS: After the introduction of the system,
      the waiting time for registration was reduced by 20%, and the waiting time at the
      internal medicine department was reduced by 15%. The benefit-to-cost ratio was
      increased to 1.34 when all intangible benefits were included in the economic
      analysis. CONCLUSIONS: The economic impact and target satisfaction rates
      increased due to the introduction of the new system. The results were proven by
      the quantitative and qualitative analyses carried out in this study. This study
      was conducted only seven months after the introduction of the system. As such, a
      follow-up study should be carried out in the future when the system stabilizes.

PMID- 23115745
TI  - Health insurance claim review using information technologies.
AB  - OBJECTIVES: The objective of this paper is to describe the Health Insurance
      Review and Assessment Service (HIRA)'s payment request (PARE) system that plays
      the role of the gateway for all health insurance claims submitted to HIRA, and
      the claim review support (CRS) system that supports the work of claim review
      experts in South Korea. METHODS: This study describes the two systems'
      information technology (IT) infrastructures, their roles, and quantitative
      analysis of their work performance. It also reports the impact of these systems
      on claims processing by analyzing the health insurance claim data submitted to
      HIRA from April 1 to June 30, 2011. RESULTS: The PARE system returned to
      healthcare providers 2.7% of all inpatient claims (97,930) and 0.1% of all
      outpatient claims (317,007) as un-reviewable claims. The return rate was the
      highest for the hospital group as 0.49% and the lowest rate was found in clinic
      group. The CRS system's detection rate of the claims with multiple errors in
      inpatient and outpatient areas was 23.1% and 2.9%, respectively. The highest rate
      of error detection occurred at guideline check-up stages in both inpatient and
      outpatient groups. CONCLUSIONS: The study found that HIRA's two IT systems had a
      critical role in reducing heavy administrative workloads through automatic data
      processing. Although the return rate of the problematic claims to providers and
      the error detection rate by two systems was low, the actual count of the returned
      claims was large. The role of IT will become increasingly important in reducing
      the workload of health insurance claims review.

PMID- 23115746
TI  - eNotification: Adapting eReferral for Public Health Notifiable Disease Reporting
      in New Zealand.
AB  - OBJECTIVES: New Zealand is currently implementing a standard for the electronic
      referral of patients from primary care to District Health Board (DHB) provided
      specialist services (eReferral). Medical Officers of Health working within DHB
      public health services receive referrals through a legally mandated disease
      notification system. Although laboratories have reported notifiable diseases
      electronically since 2007 clinical and risk factor information are still reported
      by fax or telephone. This paper describes a project that aims to adapt eReferral
      for public health purposes. METHODS: A work group of Medical Officers of Health
      was convened to develop criteria for priority disease selection and to develop
      data and functional requirements. RESULTS: Eleven out of 52 notifiable diseases
      were selected based on potential to improve public health response and or make
      referral easier for medical practitioners. In addition to identifiers and
      demographics data requirements included: symptom onset date, occupation and place
      of work (or other day time location) and workplace name. The work group specified
      that most enteric disease eReferrals should be triggered by a positive laboratory
      test. Vaccine preventable disease eReferrals should occur at the time of relevant
      laboratory test order. CONCLUSIONS: The project is at an early stage and
      consultation with referrers has been limited. The next stage will require working
      closely with referring doctors to resolve practical issues with occupation
      coding, to minimize practice workflow change, and to maintain consistency with
      other eReferral processes.

PMID- 23115747
TI  - Acute chorioamnionitis at term caused by the oral pathogen Fusobacterium
      nucleatum.
AB  - Fusobacterium nucleatum is an oral pathogen associated with preterm birth.
      Presented is a case of acute chorioamnionitis that progressed to maternal sepsis
      in a term patient with intact membranes. In addition to its role in periodontal
      disease and preterm birth, our case demonstrates that intrauterine infection with
      Fusobacterium nucleatum can result in severe disease at term.

PMID- 23115748
TI  - Pilomatricoma: an unusual dermatologic neoplasm.
AB  - Pilomatricoma is typically an isolated benign tumor of the hair follicle matrix
      with very low incidence, recurrence, and initial diagnostic accuracy. This report
      presents a case of a pilomatricoma of the left chest that was initially ignored
      due to the limited extent of access to medical care in Palau, and subsequent
      treatment for cervical cancer. The paper helps to emphasize the importance of a
      vast differential diagnosis, especially in those patients from the Pacific
      Islands.

PMID- 23115749
TI  - Attaining meaningful use of health information technology in a residency program:
      challenges and rewards.
AB  - The US Federal Government has offered financial incentives to physicians and
      hospitals for using health care technology in ways that may improve the quality
      of patient care, via the use of an electronic health record. Although many
      barriers exist to achieving the health care technology requirements necessary to
      capture these incentives, several strategies were employed by the University of
      Hawai'i Family Medicine Residency Program at the Physician Center at Mililani to
      overcome these barriers, in order to register and attest for these financial
      rewards. The rewards are substantial, and may total up to $44,000/eligible
      provider over 5 years, and $63,750/eligible provider over 6 years, for Medicare
      and Medicaid respectively. Both programs have different incentive payment
      schedules for hospital facilities. This article intends to outline the process
      and challenges involved in meeting the specific requirements necessary to qualify
      for this funding, and to assist others in this endeavor, particularly (but not
      limited to) residency training programs, which face a unique set of challenges.

PMID- 23115751
TI  - Department of Communication Sciences and Disorders at the University of Hawai'i
      John A. Burns School of Medicine.

PMID- 23115753
TI  - Perspectives of Chuukese patients and their health care providers on the use of
      different sources of interpreters.
AB  - BACKGROUND: Immigrants from Chuuk, a Pacific Island nation in Micronesia, are a
      growing population of limited-English speakers in Hawai'i. The purpose of this
      study was to examine the perspectives of Chuukese patients and their physicians
      in Honolulu, Hawai'i on interpreter services. METHODS: An anonymous multiple
      choice survey was distributed to potential patients through a Chuukese community
      group and to physicians through the Hawai'i Residency Programs to examine the
      following sources of interpreters: Family member or friend, telephone
      interpreter, or professional in-person interpreter. Statistical significance of
      cross-tabulated responses was analyzed using Fisher's exact test. RESULTS: 114
      surveys from health care providers and 95 surveys from Chuukese community members
      were analyzed after exclusion criteria. Using a family member or friend was the
      method most frequently used by physicians (78%) and Chuukese patients (71%).
      Telephone interpreters were used the least by physicians (6%) and Chuukese
      patients (2%) and both rated it poorly in terms of comfort and ease of use.
      Physicians rated professional in-person interpreters as the best method (67%)
      while Chuukese patients rated using a family member or friend as the best method
      (61%), especially among those who reported a lower English proficiency (P = .04)
      and who lived in Hawai'i for fewer years (P > .01). DISCUSSION: The preference of
      Chuukese patients for using a family member or friend as interpreter differs from
      national standards which promote the use of a professional interpreter. Given the
      preference of both physicians and Chuukese patients for in-person interpreters
      over telephone interpreters, there is a need for increased training and hiring of
      in-person interpreters.

PMID- 23115754
TI  - Transforming primary care practices in a Hawai'i Island clinic: obtaining patient
      perceptions on patient centered medical home.
AB  - Health care access is a significant problem for residents of Hawai'i Island who
      are experiencing a healthcare provider shortage crisis. Many residents must
      travel far for routine medical care, and in some cases to other islands. Hamakua
      Health Center, Inc., which operates from two clinical sites (Honokaa and Kapaau),
      is transitioning towards a Patient-Centered Medical Home care model. Through
      focus groups, a qualitative study was completed to obtain patient perceptions on
      Patient-Centered Medical Home. The Hamakua and Kohala Family Health Center staff
      were asked to recommend a list of patients from their respective health centers
      for focus group participation. In this sample (N=18), 67% of participants were
      female of various ethnicities. The participants' mean age was 62.2 (SD =14.3)
      years. Questions asked by the moderator were based on the American College of
      Providers' Patient-Centered Medical Home Assessment Tool. The three universal
      themes generated by the focus groups included quality care, provider and health
      services accessibility, and communication and coordination. Health information
      technology was a topic that was explored in the focus groups, and encompasses all
      three themes. Communication is regarded as a key to receiving quality care.
      Participants suggested having a rotation of specialists flown-in regularly from
      O'ahu to improve care quality. Technology is appreciated as it can streamline the
      information exchange process, and increase the patient's access to health
      services. There is unanimous concern regarding confidentiality and privacy. It is
      imperative that the health centers keep patients informed as they make their
      transition.

PMID- 23115755
TI  - Guaiac interpretation by non-certified clinicians.
AB  - OBJECTIVE: To assess the ability of non-certified clinicians to interpret guaiac
      test results. METHODS: 50 clinicians were shown photographs of 20 guaiac test
      cards. They were asked to classify these as positive, negative, or uncertain.
      RESULTS: 31 nurses, 4 clinical assistants, 7 emergency attending MDs, 2 resident
      MDs, and 6 medical students comprised the study group. Mean correct percentages
      for 15 clearly positive or negative guaiac test cards ranged from 87% to 96% in
      each of the above groups. Correct results were lower for five of the borderline
      positive guaiac cards. CONCLUSION: This study demonstrates that all clinician
      groups correctly interpreted the guaiac result most of the time, but there was a
      moderate error rate. This data supports the Joint Commission standard for this
      particular point of care test; clinicians interpreting guaiac testing should be
      trained with demonstrated competency.

PMID- 23115756
TI  - The Hawai'i Homeless Outreach and Medical Education Project: servicing the
      community and our medical students.

PMID- 23115760
TI  - The connection between dentistry and other medical fields.

PMID- 23115759
TI  - Targeted DNA vaccines for enhanced induction of idiotype-specific B and T cells.
AB  - BACKGROUND: Idiotypes (Id) are antigenic determinants localized in variable (V)
      regions of Ig. Id-specific T and B cells (antibodies) play a role in
      immunotherapy of Id(+) tumors. However, vaccine strategies that enhance Id
      specific responses are needed. METHODS: Id(+) single-chain fragment variable
      (scFv) from multiple myelomas and B cell lymphomas were prepared in a fusion
      format that bivalently target surface molecules on antigen-presenting cells
      (APC). APC-specific targeting units were either scFv from APC-specific mAb (anti
      MHC II, anti-CD40) or chemokines (MIP-1alpha, RANTES). Homodimeric Id-vaccines
      were injected intramuscularly or intradermally as plasmids in mice, combined with
      electroporation. RESULTS: (i) Transfected cells secreted plasmid-encoded Id(+)
      fusion proteins to extracellular fluid followed by binding of vaccine molecules
      to APC. (ii) Targeted vaccine molecules increased Id-specific B and T cell
      responses. (iii) Bivalency and xenogeneic sequences both contributed to enhanced
      responses. (iv) Targeted Id DNA vaccines induced tumor resistance against
      challenges with Id(+) tumors. (v) Human MIP-1alpha targeting units enhanced Id
      specific responses in mice, due to a cross reaction with murine chemokine
      receptors. Thus, targeted vaccines designed for humans can be quality tested in
      mice. (vi) Human Id(+) scFv from four multiple myeloma patients were inserted
      into the vaccine format and were successfully tested in mice. (vii) Human MIP
      1alpha vaccine proteins enhanced human T cell responses in vitro. (viii) A
      hypothetical model for how the APC-targeted vaccine molecules enhance Id-specific
      T and B cells is presented. CONCLUSION: Targeted DNA Id-vaccines show promising
      results in preclinical studies, paving the way for testing in patients.

PMID- 23115761
TI  - Comparison of two different veneer preparation designs in vital teeth.
AB  - OBJECTIVE: To compare the clinical performance of two different veneer
      preparation designs (overlap and nonoverlap) on anterior veneer restorations in
      vital teeth in a retrospective clinical study. METHOD AND MATERIALS: In this
      study, 292 anterior all-ceramic veneer restorations in vital teeth were
      clinically examined in 74 patients. The preparation designs were categorized by
      the amount of tooth reduction on the final casts, with 245 in the overlap and 47
      nonoverlap group. RESULTS: After a mean +/- SD observation time of 124.25 +/-
      60.61 months, 20 failures occurred. All failures occurred in the overlap design.
      Restorations with nonoverlap preparation designs showed significantly fewer
      failures than restorations with overlap preparation design (P = .018, log-rank).
      CONCLUSION: Based on the findings of this study, whenever feasible, a preparation
      design without incisal overlap is recommended, especially in vital teeth..

PMID- 23115762
TI  - Patient-centered outcomes after subepithelial connective tissue grafts and
      coronally advanced flaps.
AB  - OBJECTIVE: The use of a coronally advanced flap (CAF) and connective tissue graft
      (CTG) is a well-established procedure to cover single and multiple recessions and
      improve soft tissue esthetics. However, until now, there are still limited data
      evaluating patient morbidity, the fear of imminent tooth loss, and modification
      of sensitivity in surgical areas. The aim of the present study was to evaluate
      the patient-centered outcomes associated with CAF + CTG. METHOD AND MATERIALS:
      Thirty-four patients (mean age, 30.76 +/- 6.88 years) with single or multiple
      Class I and II gingival recessions were treated using a CAF + CTG. The following
      parameters were evaluated at 14 days and 1, 3, 6, and 12 months after surgery:
      esthetics, root hypersensitivity, fear of imminent tooth loss, daily activities
      or nutritional habits, and the levels of postsurgical morbidities. A visual
      analog scale was used to evaluate patient-centered outcomes. The percentage of
      patients belonging to each of the severity scales, the mean values associated
      with each parameter, and the statistical significance of the modification of the
      monitored parameters were calculated. The parametric F (Fisher) test and the
      least significant difference post hoc pair-wise comparisons were computed.
      RESULTS: There were statistically significant differences between baseline and
      all follow-up time points in root hypersensitivity and in fear of tooth loss.
      Preoperative prevalence of fear of tooth loss was 99%. Esthetics were
      statistically significantly improved at the 1-, 3-, 6-, and 12-month visits
      compared with the evaluation at 14 days. No palatal bleeding was recorded. The
      pain perception in the donor area was mild: Only 3% of patients reported severe
      palatal pain, and the mean VAS score for palatal pain was 3.79 +/- 1.49.
      CONCLUSION: Treatment of single and multiple gingival recessions with CAF + CTG
      resulted in predictable improvements of soft tissue esthetics and root
      hypersensitivity but was associated with a slight increase in patient morbidity,
      mainly related to the harvesting of CTG. This should be considered when treating
      patients with esthetic demands.

PMID- 23115763
TI  - Multidisciplinary approach to the establishment and maintenance of an esthetic
      smile: a 9-year follow-up case report.
AB  - In addition to providing functionality to patients, contemporary dentistry
      strives for esthetic excellence. Patients with anterior impairments, such as
      shape, size, and position alterations, have compromised smile harmony. A
      multidisciplinary orthodontic-operative dentistry approach has improved the
      treatment of these patients, since the use of orthodontic appliances in
      association with direct composite restorations can solve many esthetic problems.
      Although this treatment strategy is rather widespread, professional skills are
      necessary for the correct reproduction of the main features of teeth. Moreover,
      treatment success is directly related to its longevity. With the aid of a 9-year
      follow-up case report, a simple direct technique associated with an orthodontic
      treatment for restoring the esthetic appearance of an impaired smile, with good
      short- and long-term outcomes, based on minimal but essential esthetic repair
      interventions is discussed. Such coordinated treatment proved to be effective for
      the establishment and maintenance of an esthetic and pleasant smile.

PMID- 23115764
TI  - Challenges of restoring an anterior maxillary tooth: the impact of fluorescence
      and the mock-up approach.
AB  - Nowadays, esthetic demand stimulates optimized optical features that offer
      satisfactory masking effects, particularly in anterior restorations. In cases in
      which only a single tooth is involved, the treatment is one of the most
      challenging of all esthetic restorations. The optical characteristics of the
      natural teeth are essential to masking the restoration and are determined by the
      interaction of light and dental substrates with varying degrees of translucency
      and opacity. Additionally, form and superficial texture are important in terms of
      ensuring the natural harmony of the dental restoration. Thus, technical
      approaches, such as mock-up and composite resin stratification, have led to
      favorable outcomes. This case report describes an easy and reliable restorative
      procedure of a maxillary central incisor that focuses on achieving a natural
      appearance by using an adequate direct composite resin restoration.

PMID- 23115765
TI  - Clinical study on the closure of extraction wounds of partially soft tissue
      impacted mandibular third molars.
AB  - OBJECTIVE: When a mandibular third molar is partially impacted in the soft
      tissue, it must be determined whether the extraction wound should be left
      partially open or completely closed. We hypothesize that a blood clot preserving
      a surgical wound with easily cleanable surfaces by primary closure and drain
      application would postoperatively minimize dry socket and/or alveolitis
      development. METHOD AND MATERIALS: Twenty patients requiring bilateral extraction
      of partially soft tissue-impacted mandibular third molars in a vertical position
      were included in the study. The existence of dry sockets, alveolitis, pain,
      facial swelling, and trismus were evaluated on the second, fifth, and seventh
      days of the postoperative period. RESULTS: On the second day, pain, trismus, and
      swelling were higher in the drained group; however, pain reduced progressively in
      the drained group over time. There were no cases of dry sockets or alveolitis
      except for a single patient on the seventh day in the drained group over the 7
      day study period. On the other hand, in the secondary closure group, the number
      of dry sockets was 8 (40%) on the second day. The number of alveolitis was 10
      (50%) on the fifth day and 4 (20%) on the seventh day. CONCLUSION: Closed healing
      by drain insertion after removal of partially soft tissue-impacted third molars
      produces less frequent postoperative dry sockets and/or alveolitis development
      than occurs with open healing of the surgical wound. In cases with a risk of
      alveolitis development (lack of oral hygiene, immunocompromised patients, etc),
      it can be avoided with the "kiddle effect" and related undesired complications by
      implementing closed healing with drain insertion.

PMID- 23115766
TI  - Allergic reactions associated with metal alloys in porcelain-fused-to-metal fixed
      prosthodontic devices-A systematic review.
AB  - OBJECTIVE: To systematically review the allergic reactions associated with metal
      alloys in porcelain-fused-to-metal (PFM) fixed prosthetic devices. METHOD AND
      MATERIALS: After reviewing the titles and abstracts of the articles as well as
      removing duplicates, 22 articles were considered relevant. PubMed, Web of
      Science, ScienceDirect, and Google Scholar from 1970 to 2012 were evaluated, and
      randomized studies, review articles, case reports, cross-sectional surveys, and
      abstracts were included. Conference papers and posters were excluded. RESULTS:
      Although reported, allergic reactions to metallic alloys in the context of PFM
      devices are not well documented. Allergic reactions to high noble and noble metal
      alloy cores of palladium and gold and to base metal alloys nickel and cobalt in
      the context of PFM fixed partial dentures (FPDs) are reported. Each type of metal
      is associated with a different rate of allergic reactions, which may be
      attributed to the extent of corrosion of the alloy, population exposure, and the
      biologic environment. Because few studies document allergic reactions to metals
      that comprise PFM crowns and partial dentures, further research in this field is
      necessary to determine the frequency and type of reactions elicited. CONCLUSION:
      Though allergic reactions to metal alloys used in dentistry are well documented,
      only few articles focus on the correlation between FPDs and metal allergies.
      Thus, this paper surveys case reports of hypersensitivity reactions linked to
      FPDs and reviews the current literature on allergic reactions to the metallic
      elements comprising those devices.

PMID- 23115767
TI  - Periodontal status in post-liver transplantation patients: 10 years of follow-up.
AB  - OBJECTIVE: To compare the current (t1) periodontal status of post-liver
      transplantation patients to their status 10 years earlier (t0). METHOD AND
      MATERIALS: Seventeen patients 45 to 71 years of age who were evaluated
      approximately 10 years previously were enrolled in the study. All subjects had
      undergone a liver transplantation 1 to 10 years prior to the initial examination
      (t0). Clinical and radiographic parameters were recorded for the Ramfjord Index
      teeth and compared between t0 and t1, including Plaque Index (PI), Gingival Index
      (GI), probing depth (PD), clinical attachment level (CAL), and gingival
      overgrowth (GO). Bone loss was measured on digitized images of panoramic
      radiographs. RESULTS: Mean PI, GI, CAL, and GO were slightly lower at t1 than at
      t0; however, these differences were not statistically significant (P > .05,
      Student t test for paired observations). The mean PD was reduced at t1 (2.43 +/-
      0.18 mm) compared with t0 (3.35 +/- 0.22 mm), which was statistically significant
      (P = .001, Student t test for paired observations). To the contrary, the mean
      radiographic bone loss at t1 was higher than at t0 (5.61 vs 4.48 mm,
      respectively), which was also statistically significant (P = .017). Tooth loss
      was observed in some of these patients, ranging from 0 to 4 during the 10 years
      of follow-up, which amounted to an annual rate of 0.24 teeth per patient.
      CONCLUSION: Post-liver transplantation patients maintained stable clinical
      periodontal parameters during a 10-year period; however, some radiographic bone
      loss occurred during this time.

PMID- 23115768
TI  - A comparative clinical study on human tooth extractions: flap vs flapless buccal
      surgery.
AB  - This study assessed the viability of bone and soft tissue healing at the wound
      extraction site, when the wound was both covered and not covered with a
      mucoperiosteal flap. In total, 40 patients were enrolled in the clinical study
      and were randomly allocated to each treatment cohort group.

PMID- 23115769
TI  - The influence of chlorhexidine on the antibacterial effects of MTA.
AB  - OBJECTIVE: To investigate the influence of chlorhexidine in different
      concentrations when mixed with mineral trioxide aggregate gray (MTA-G) or white
      (MTA-W). The antibacterial effect on Enterococcus faecalis was used as the
      primary parameter. METHOD AND MATERIALS: Similar to the agar diffusion test,
      Mueller-Hinton agar plates were inoculated with E faecalis (ATCC 19433), and 14
      groups (n = 21) were prepared. The specimens consisted of MTA-W and MTA-G, and
      these were enriched with chlorhexidine concentrations of 0.1%, 0.2%, 0.5%, 1.0%,
      1.5%, and 2.0%. Pure MTA-W and MTA-G (each combined with distilled water) were
      used as controls. After incubation periods of 24 and 48 hours, the inhibiting
      areolae were measured. RESULTS: Pure MTA-W, in contrast to pure MTA-G, had no
      bactericidal effects. With increasing chlorhexidine concentrations of up to 1.5%,
      a linear increase in bactericidal activity was observed. In contrast, MTA-G
      showed only a low self-bactericidal influence, and the antibacterial effects with
      increasing chlorhexidine concentrations were significantly lower than those of
      MTA-W (P < .001). CONCLUSION: When mixed with distilled water, pure MTA-G
      revealed a low bactericidal effect against E faecalis. The use of chlorhexidine
      with MTA mixtures leads to an antibacterial effect against E faecalis, and within
      the first 48 hours, this effect is significantly higher in combination with MTA-W
      when compared with MTA-G.

PMID- 23115770
TI  - Comparison of nutrient intake between patients with periodontitis and healthy
      subjects.
AB  - OBJECTIVE: Recent studies have shown that inflammatory diseases can be influenced
      by nutritional factors. For this reason, this study was designed to evaluate the
      food intake of patients with periodontal disease in comparison to healthy
      subjects using a 7-day food record (7-DFR). METHOD AND MATERIALS: The study
      population consisted of 42 patients with chronic periodontitis and 38 healthy
      subjects (controls). Periodontitis was diagnosed by using the Plaque Index,
      Sulcus Bleeding Index, and measurement of probing depth. All participants
      completed a 7-DFR, which was analyzed with DGE-PC Professional 2.7. To confirm
      the nutritional analysis, the vitamin C plasma level of each participant was
      measured. Additionally, the oral discomfort of patients with periodontal disease
      was ascertained by using an additional questionnaire. RESULTS: Analysis of the 7
      DFR revealed that patients with periodontitis had significantly lower intake
      rates of vitamin C, folic acid, magnesium, and fiber than those of healthy
      controls. The mean vitamin C plasma levels were significantly lower in patients
      with periodontitis (0.63 mg/dL) compared with healthy control subjects (1.13
      mg/dL, P < .05). Evaluation of the questionnaire showed that approximately 50% of
      patients experienced discomfort while eating. CONCLUSION: The present study shows
      that patients with periodontitis have a reduced intake of vitamin C, folic acid,
      magnesium, and fiber compared with healthy subjects. This is possibly an outcome
      of oral discomfort during mastication. To avoid an insufficient nutrient supply
      for a patient with periodontal disease, the patient's choice of foods should be
      closely monitored.

PMID- 23115771
TI  - Effect of laser irradiation on root canal walls after final irrigation with 17%
      EDTA or BioPure MTAD: X-ray diffraction and SEM analysis.
AB  - OBJECTIVE: To evaluate the effect of diode laser irradiation on crystallographic
      and morphologic characteristics of root canal walls after final irrigation with
      either 17% EDTA or BioPure MTAD. METHOD AND MATERIALS: Root canals in 60 single
      rooted teeth were instrumented using a rotary Ni-Ti system. The teeth were
      randomly divided into three groups (n = 20) based on the final irrigants: group
      1, saline; group 2, 17% EDTA; and group 3, MTAD. Each group was further divided
      into two subgroups (n = 10). Subgroup A received diode laser irradiation at a
      wavelength of 810 nm and an output power of 2 W for 5 * 5 seconds, while subgroup
      B received no irradiation. A paired t test was used to compare mean dentinal
      erosion before and after irradiation in each group. Specimens were analyzed using
      SEM and x-ray diffractometery. One-way ANOVA and a post hoc Tukey test were used
      to evaluate dentinal erosion between groups. Kruskal-Wallis and Mann-Whitney U
      tests were used to evaluate any significant differences in the amount of dentin
      erosion between the groups. RESULTS: SEM micrographs showed closed dentinal
      tubules in the control group, while in unlased BioPure MTAD and EDTA groups,
      clean root canal walls were evident. Erosion was mostly seen in EDTA-treated
      teeth, while an increase of erosion degree was noted on root canal walls after
      additional laser irradiations. After irrigation and laser irradiation, the XRD
      spectrums indicated sharper peaks of EDTA, which showed a slight crystallographic
      change compared with the other groups. EDTA made changes in the mineralization of
      dentin due to its higher accumulation on the dentinal wall surface and produced
      significant degrees of erosion in comparison with MTAD by changing the physical
      properties of the root canal wall surface. These undesirable changes can be
      enhanced by further laser irradiation. CONCLUSION: Results confirm that a diode
      laser in combination with BioPure MTAD have minimum effect on the chemical
      properties of root canal dentin while having good smear layer removal properties.
      The results of the present study indicated that a diode laser in combination with
      Biopure MTAD might be suggested as a final management of the root canal system
      prior to canal obturation.

PMID- 23115772
TI  - Comparison of the effects of periodontal rotary instruments and Gracey curettes
      on root surface characteristics: an in vivo SEM study.
AB  - OBJECTIVE: Preparing the root surface by planing is an important procedure in the
      treatment and prevention of periodontal disease. The present study was designed
      to compare root surface characteristics following root planing with hand and
      power-driven instruments. METHOD AND MATERIALS: In the present study, 40 single
      rooted teeth indicated for extraction were selected and divided into two groups
      according to whether hand or rotary instruments were used (group I or II,
      respectively). Teeth were randomly selected. Scaling was performed with
      ultrasonic instruments. A mucoperiosteal flap was raised to the level of the
      alveolar crest, and root planing was done with hand instruments for the teeth in
      group I and with a rotary bur for the teeth in group II. Subsequently, the
      instrumented teeth were extracted, and the resulting surfaces were evaluated
      under a scanning electron microscope. RESULTS: In group I, deep scratches and
      striae were present. Considerable loss of tooth substance was observed, with a
      mean value of 1.57 +/- 0.45. In group II, the root surface appeared flat and
      smooth, with fewer signs of gouging or scratching, with a mean value of 0.68 +/-
      0.49. The results were highly significant when both groups were compared (P =
      .001). CONCLUSION: In the present study, although both instruments used were
      found to be effective in removing deposits from the root surfaces, the results
      favored the use of rotary instruments over hand instruments for root planing to
      achieve a smooth, clean root surface.

PMID- 23115773
TI  - Graphene and its derivatives for cell biotechnology.
AB  - Every few years, a novel material with salient and often unique properties
      emerges and attracts both academic and industrial interest from the scientific
      community. The latest blockbuster is graphene, an increasingly important
      nanomaterial with atomically thin sheets of carbon, which has become a shining
      star and has shown great promise in the field of material science and
      nanotechnology. In recent years, it has changed from being the exclusive domain
      of physicists to the new passion of chemists and biologists. Graphene and its
      derivatives are now at the forefront of nearly every rapidly developing field of
      science and engineering, including biochemistry, biomedicine and certain cutting
      edge interdisciplines that have intense popularity. The aim of this review is,
      firstly, to provide readers with a comprehensive, systematic and in-depth
      prospective of graphene's band structure and properties, and secondly, to
      concentrate on the recent progress in producing graphene-based nanomaterials,
      including mechanical exfoliation, chemical vapor deposition, plasma enhanced
      chemical vapor deposition, chemical reduction of graphene oxide, total organic
      synthesis, electrochemical synthesis and other fabrication strategies widely
      accepted by research scientists. At the same time, important definitions related
      to graphene are also introduced. The focus of this Tutorial Review is to
      emphasize the current situation and significance of using this new kind of two
      dimensional material in the hot and emerging fields that are closely related to
      human life quality, for instance, cell biochemistry, bioimaging along with other
      frontier areas. Finally, the latest developments and possible impact that affect
      the heart of the whole scientific community have been discussed. In addition, the
      future trends along with potential challenges of this rapidly rising layered
      carbon have been pointed out in this paper.

PMID- 23115774
TI  - Improved stabilities on surface-enhanced Raman scattering-active Ag/Al2O3 films
      on substrates.
AB  - As is shown in the literature, surface-enhanced Raman scattering (SERS)-active Ag
      films obtained by the salting-out of Ag colloids from solutions with some salts,
      are popularly used to examine the structure of analytes. SERS-active Ag
      nanoparticles (NPs) demonstrate more significant SERS effects than Au NPs,
      however, problems regarding the stabilities of SERS-active Ag NPs remain to be
      overcome. In this work, Ag/Al(2)O(3) colloids were prepared in 0.1 M HNO(3)
      solutions containing Al(2)O(3) NPs with higher heat capacity by
      sonoelectrochemical methods. SERS-active Ag/Al(2)O(3) films deposited on glass
      slides were prepared by the addition of a saturated NaCl solution in the prepared
      Ag/Al(2)O(3) colloids-containing solution. In an acceptable sacrifice of Raman
      intensity by ca. 30% magnitude, the prepared Ag/Al(2)O(3) films markedly improved
      thermal stability by raising the operation temperature over 100  degrees C,
      compared to Ag films. Meanwhile, aging of SERS enhancement capability in an
      atmosphere of relative humidity (RH) of 50% and 20% (v/v) O(2) at 30  degrees C
      is significantly depressed using Ag/Al(2)O(3) films.

PMID- 23115775
TI  - Ion-molecule reactions for the differentiation of primary, secondary and tertiary
      hydroxyl functionalities in protonated analytes in a tandem mass spectrometer.
AB  - A mass spectrometric method utilizing gas-phase ion-molecule reactions of 1
      butanethiol and di-tert-butyl peroxide has been developed for the differentiation
      of primary, secondary and tertiary hydroxyl functionalities in protonated
      analytes in a FT-ICR mass spectrometer.

PMID- 23115776
TI  - [Not Available].

PMID- 23115777
TI  - [Not Available].

PMID- 23115778
TI  - [Not Available].

PMID- 23115779
TI  - [Being a physician. . . "and having been established Nephrology in Spain"].

PMID- 23115780
TI  - Carers of patients with early-onset dementia, their burden  and needs: a pilot
      study using a new questionnaire--care-EOD.

PMID- 23115782
TI  - Abstracts of the VI Symposium on Maternal-Fetal Interaction, Sao Paulo, Brazil,
      and the First Latin-American ASRI (American Society for Reproductive Immunology)
      Satellite Symposium, Buenos Aires, Argentina. November 2011.

PMID- 23115781
TI  - Predictors of emergency commitment for nursing home  residents: the role of
      resident and facility characteristics.
AB  - OBJECTIVES: The ability of nursing homes to manage the mental health needs of
      their residents is crucial to providing high quality care. An important element
      is preventing exacerbations of psychiatric conditions that trigger discharge from
      the nursing home (NH) because of an emergency commitment (EC) for an involuntary
      psychiatric examination. The objective of this study was to examine the
      relationship between resident and facility characteristics and the risk of EC for
      involuntary psychiatric examination among Medicaid-enrolled NH residents in
      Florida. DESIGN: This retrospective cohort study employed 2.5 years (31 December
      2002 through 30 June 2005) of Medicaid enrollment and fee-for-service, pharmacy,
      and involuntary commitment data to examine resident characteristics. NH
      characteristics were obtained from the Online Survey Certification and Reporting
      database. SETTING: Medicaid-certified NHs in Florida (N= 584). PARTICIPANTS:
      Medicaid-enrolled NH residents (N= 32,604). RESULTS: Younger age, male gender,
      having dementia, having a serious mental illness (SMI), and residing in a for
      profit facility were all independently associated with the greater risk of EC.
      Although most residents with EC were prescribed psychotropic medication, less
      than half received non-pharmacological behavioral health outpatient services
      before or after their involuntary psychiatric examination. CONCLUSION: Our
      findings highlight the salience of resident and facility characteristics to
      prevalence rates of EC for involuntary psychiatric examinations among NH
      residents and underscore a need for increased education, communication, and
      future research on the predictive factors as well as the consequences of these
      adverse events.

PMID- 23115783
TI  - FDA reforms hampered by budget freeze.

PMID- 23115784
TI  - Violence against doctors in Egypt leads to strike action.

PMID- 23115785
TI  - Profile: NCATS--new kids on the block.

PMID- 23115786
TI  - Riding the waves: optimism and realism in the treatment of TB.

PMID- 23115787
TI  - Abstracts of Personalizing Cancer Diagnosis and Treatment 2012. October 20-21,
      2012.

PMID- 23115788
TI  - Discovery of the novel HLA-DRB1*10:04 allele in a Taiwanese volunteer bone marrow
      donor and identification of the probable HLA-A, -B, -C and -DRB1 haplotype in
      association with DRB1*10:04.
AB  - We report here a novel variant of HLA-DRB1*10, DRB1*10:04, discovered in a
      Taiwanese volunteer bone marrow donor by a sequence-based typing (SBT) method.
      The DNA sequence of DRB1*10:04 differs from DRB1*10:01:01, in exon 2, at
      nucleotide positions 296 (G fi A) and 303 (T fi G). The nucleotide changes caused
      an amino acid substitution at amino acid residue 70 (R fi Q). We hypothesize that
      the formation of DRB1*10:04 was probably the result of a gene recombination event
      where DRB1*10:01:01 received a minimum length of DNA sequence from DRB1*04:05:01,
      as the sequence of DRB1*10:04 is identical to DRB1*10:01:01 in exon 2 except the
      sequence from nucleotide 296 to nucleotide 303, which is identical to
      DRB1*04:05:01. The plausible HLA-A, -B, -C and - DRB1 haplotypes in association
      with DRB1*10:04 was deduced as A*01:01-B*37:01-C*06:02-DRB1*10:04.

PMID- 23115789
TI  - The features of late local recurrences following curative surgery for rectal
      cancer.
AB  - BACKGROUND/AIMS: Rectal cancers are characterized by high incidence of local
      recurrence after curative surgery, in some cases it occurs after 5 years. To
      determine the features of late locally recurrent rectal cancer (LRRC) is
      important for its management. METHODOLOGY: The medical records of 110 patients
      with LRRC after curative surgery were reviewed. We examined the relationship
      between the interval between surgery and appearance of LRRC and various
      clinicopathological factors by dividing patients into the early (recurrence
      before 5 years after surgery) and late (recurrence after more than 5 years)
      recurrence groups. RESULTS: In the late-recurrence group (n=7), well
      differentiated adenocarcinoma was significantly higher (p=0.0031) and venous
      invasion was significantly lower (p=0.0105) than the early-recurrence group
      (n=113). Multivariate Cox regression analysis identified histological grade and
      venous invasion of primary lesion as independent predictors for early-onset LRRC
      (p=0.0396 and p=0.0009, respectively). The presence of symptoms at the time of
      diagnosis was the only factor that significantly related to resectability of LRRC
      (p=0.015). CONCLUSIONS: For detection of asymptomatic LRRC, which can lead to
      curative resection, follow-up program after curative resection of rectal cancer
      should be designed based on the histological grade and venous invasion of primary
      tumor.

PMID- 23115790
TI  - Quality of cancer registry data: completeness of TNM staging and potential
      implications.

PMID- 23115791
TI  - Completeness of colon and rectal cancer staging in the Danish Cancer Registry,
      2004-2009.

PMID- 23115792
TI  - Cytokine expression and the role of Thl7 cells in mice colitis.
AB  - BACKGROUND/AIMS: To explore the expression and mechanism of Thl7 cells and
      cytokines in mice model with 2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced
      inflammatory bowel disease (IBD). METHODOLOGY: ELISA assay was used to detect the
      expression of Th17 cytokine IL-17 and Thl cytokines IFN-y in colon tissues.
      Western blot assay was applied to detect IL-17 expression in peripheral blood
      mononuclear cells (PBMC), spleen mononuclear cells (SMC), mesenteric lymph node
      cells and colon tissue of colitic mice. RT-PCR assay was used to detect the
      effect of anti-IL-17 antibody application on TNF-a, IFN-y and IL-6 mRNA levels in
      SMCs from colitic mice. RESULTS: Th17 cytokine IL-17 and Thl cytokines IFN-y were
      both expressed at high level in TNBS-induced colitic mice. In addition, the
      expression of Thl7 cytokine appeared earlier than the Thl cytokine. IL-17 levels
      in SMCs, mesenteric lymph node cells and colon tissue of the disease model group
      had significant differences compared with normal control group (p<0.01), while
      the IL-17 level in PBMCs of the disease model group had no significant difference
      (p>0.05) to control group. After application of 10 ug/mL anti-IL-7 antibody, the
      TNF-ct, IL-6 and IFN-y mRNA levels in SMCs of the model group showed no
      significant difference from that of no antibody group (p>0.05). CONCLUSIONS: Both
      Th17 cells and Thl cells involved in TNBS-induced IBD and the role of Thl17 cells
      may be through inducing the secretion of pro-inflammatory cytokines.

PMID- 23115793
TI  - Factors influencing quality of life after abdominal surgery for Crohn's disease.
AB  - BACKGROUND/AIMS: Although fecal diversion is reported to improve the quality of
      life (QOL) of the patients with active perianal disease, the effect of the
      concomitant abdominal surgery was not well studied. The aim of this study was to
      investigate factors that impair postoperative QOL of patients with Crohn's
      disease. METHODOLOGY: A SF-36v2 questionnaire was mailed to patients who
      underwent abdominal operation between January 2001 and February 2007. Patients
      were also asked about the medical therapy they were receiving. RESULTS: Data from
      50 patients were analyzed. Univariate analyses revealed that patients with active
      perianal disease had lower scores for role physical, bodily pain and social
      functioning than did patients without it. Social functioning and role emotional
      scores were lower in patients older than 40 years than in those younger. The
      physical component summary score was significantly affected in patients with
      active perianal disease. Fecal diversion had no effect on QOL after abdominal
      surgery for Crohn's disease. Multivariate analysis showed that the physical
      component summary score was significantly lower in patients with active perianal
      disease than in patients without it. CONCLUSIONS: Active perianal disease is an
      important factor that impairs QOL in patients who have undergone surgery for
      intestinal Crohn's disease.

PMID- 23115794
TI  - Does a decrease of NK cells in the appendix increase the risk of developing colon
      cancer?
AB  - BACKGROUND/AIMS: Epidemiological studies indicate that relevance between appendix
      and colon cancer is controversial, but unfortunately, there is no data based on
      examination of immune indicator to reveal the relativity. METHODOLOGY: This study
      explored the relation-ship between appendix immunity and the right colon cancer
      by detecting the presence of NK cells in appendix tissues with
      immunohistochemistry. RESULTS: The number of NK cells in the appendix tissue was
      the highest in patients with appendix inflammation (37.2+1.1), while lowest in
      patients with colon cancer and normal appendix (30.9+1.7). CONCLUSIONS: The
      decrease of NK cells in the appendix tissue is correlated with the increased
      incidence of right colon cancer.

PMID- 23115796
TI  - Bibliography. Gastroenterology and nutrition (GI). Current world literature.

PMID- 23115795
TI  - Abstracts of the Annual Meeting of the American Society of Plastic Surgeons.
      October 26-30, 2012. New Orleans, Louisiana, USA.

PMID- 23115798
TI  - Abstracts of the Joint Meeting of the COSA (Clinical Oncological Society of
      Australia) 39th Annual Scientific Meeting and IPOS 14th World Congress of Psycho
      Oncology. November 13-15, 2012. Brisbane, Australia.

PMID- 23115797
TI  - In a well presented report of bilateral renal pelvic thrombus formation with
      subsequent bilateral ureteral obstruction. Introduction.

PMID- 23115799
TI  - Block of red blood cell maturation in acute erythroid leukemia.

PMID- 23115815
TI  - [My technique: Key point in the surgery of ventricular septal perforation].

PMID- 23115816
TI  - [Theoretical perspectives on coping with illness in the family].

PMID- 23115817
TI  - [Current status and problem of vaccination policy in Japan].

PMID- 23115818
TI  - [Diagnosis and treatment of oral disease].

PMID- 23115819
TI  - [Infective endocarditis with artificial heart valves following Bentall, reAVR and
      MVR operations, dissection  of an abscess of the left ventricular myocardium and
      reconstruction].

PMID- 23115821
TI  - [Let use take iPad to academic meetings].

PMID- 23115820
TI  - [Imaging diagnosis Q & A. Pulmonary cancer and abnormal morphology of the
      pulmonary veins].

PMID- 23115822
TI  - [Ethical and legal principles for the activities of bioprospection in relation to
      human beings and the human genome].
AB  - During recent decades, bioprospecting has become an important field of research,
      which looks for development alternatives, entry into global (environmental)
      markets, and the subsequent obtention of benefits under sustainable development
      principles. However, there is still so much to discuss regarding the social and
      environmental impacts produced by this activity, as well as its main limitations.
      To this end, the Forum/round-table discussion, entitled "Bioprospeccion, Etica y
      Sociedad" was organised to take place on 28 March 2012 at the National University
      of Colombia. Its main objective was to enrich our knowledge on bioprospecting
      considering the ethical considerations that involve society. The presentation
      given by Professor ROMEO CASABONA, regarding the connection between
      bioprospecting and the human genome deserves special attention and is presented
      below.

PMID- 23115823
TI  - [Triploid cloned human embryos: ethical, social, and legal aspects].
AB  - This work attempts to place the experiment within the scientific and social
      framework of pluripotent-stem-cell research and offer reflections of an ethical
      and (to a lesser extent) legal nature on the results obtained by this research
      group. To these ends, the work is divided into two parts. The first part
      describes the most important aspects of Noggle and Egli's announcement and the
      biotechnological and media context in which it was made. The second part is
      concerned with the bioethical issues raised by the experiment. There are
      basically four issues, which relate to: (1) the nuclear transfer technique, (2)
      the use of human ovules to carry out the experiment, (3) the destruction of human
      blastocysts, and (4) the ethical requirements of scientific publications.

PMID- 23115824
TI  - [Information sheet and informed consent in biomedical research with samples].
AB  - This paper examines from a practical perspective, the content of the information
      sheet to the participant in a clinical trial in which pharmacogenetic studies are
      conducted and/or pharmacogenomics, and scope of informed consent. The text is
      accompanied by a guide of questions to assess the fit of a participant
      information sheet on the regulation of clinical trials, biological samples and
      protection of personal data.

PMID- 23115825
TI  - Which lessons can we learn from the European Union legal framework of medicines
      for the regulation of direct-to-consumer genetic tests?
AB  - The legal framework of the European Union (EU) for regulating access to and
      supply of direct-to-consumer (DTC) genetic tests is very liberal compared to the
      legal and regulatory framework for (internet) medicines. Nevertheless, both
      health related products can cause equally serious damage to the well being of
      individuals. In this contribution we examine whether the legal framework of the
      EU for the safety and responsible use of (internet) medicines could be an example
      for regulating access to and supply of DTC genetic tests. The EU laws governing
      medicines can, notwithstanding their shortcomings, serve as an example for
      (central) authorising the marketing of DTC genetic tests on the internal market
      in accordance with strict criteria regarding predictive value and clinical
      usefulness. Furthermore, a legal framework controlling DTC genetic tests also
      should introduce system supervision as well as quality criteria with respect to
      the information to be provided to consumers in order to enhance health
      protection. However, DTC genetic tests purchased through online ordering are
      difficult to supervise by any agency. Adequately protecting individuals against
      questionable testing kits calls for international vigilance and comprehensive
      measures by the international community. For Europe, it is important to rank the
      regulation of DTC genetic tests on the European regulatory agenda.

PMID- 23115826
TI  - International biomedical law in search for its normative status.
AB  - The broad and multifaceted problem of global health law and global health
      governance has been attracting increasing attention in the last few decades. The
      global community has failed to establish international legal regime that deals
      comprehensively with the 'technological revolution'. The latter has posed complex
      questions to regions of the world with widely differing cultural perspectives. At
      the same time, an increasing number of governmental and non-state actors have
      become significantly involved in the sector. They use legal, political, and other
      forms of decision-making that result in regulatory instruments of contrasting
      normative status. Law created in this heterogeneous environment has been said to
      be fragmented, inconsistent, and exacerbating uncertainties. Therefore, claims
      have been made that a centralised and institutionalised system would help address
      the problems of transparency, legitimacy and efficiency. Nevertheless, little
      scholarly consideration is paid to the normative status of international
      biomedical law. This paper explores whether formalisation and
      "constitutionalisation" of biomedical law are indeed inevitable for its
      establishment as a separate regulatory regime. It does so by analysing the
      proliferation of biomedical law in light of two the theory of fragmentation and
      the theory of global legal pluralism. Investigating the problem in this way helps
      determine the theoretical framework and methodology of future studies of
      biomedical law at the international level. This in turn should help its future
      development in a more consistent and harmonised manner.

PMID- 23115827
TI  - [Critical Study of the last jurisprudence of the Supreme Court on requirements
      and guarantees regarding DNA sampling from suspects].
AB  - A critical study will be made of recent jurisprudence of Spanish Supreme Court in
      relation to the principal requirements that current legislation establishes for
      so-called "DNA testing", specially in connection with the rules on lawful
      evidence. In particular, the various hypotheses and circumstances that might
      concur in the collection of tissue samples from the suspect will be analyzed, as
      well as questions relating to the need, or otherwise, of legal assistance during
      such an act.

PMID- 23115828
TI  - Ethical aspects of informed consent for the collection, preservation and use of
      cells and tissues in biological banks for research purposes.
AB  - This article explores the current and proposed requirements for informed consent
      for research with biological samples. The establishment of biobanks and the
      capabilities of collecting, storing, and using cells and tissues for research
      purposes have noticeably grown. With new abilities come new challenges to ethical
      questions of consent, specifically concerning genetic information, and
      unanticipated usage. This paper summarizes these issues in the context of levels
      of informed consent, subject risk, individual vs. societal benefits, anonymity,
      legal consensus.

PMID- 23115829
TI  - [Royal Decree 1716/2011, dated November 18, establishing the basic requirements
      of authorization and functioning of biobanks for biomedical research and the
      management of human biological samples, and regulating the functioning and
      organization of the National Registry of Biobanks for biomedical research].

PMID- 23115830
TI  - Three ways to increase productivity.

PMID- 23115831
TI  - Focusing on the patient experience.

PMID- 23115832
TI  - Get faster access to critical information.

PMID- 23115833
TI  - Mythbusters.

PMID- 23115834
TI  - I.V. integration helps clinicians reduce medication errors.

PMID- 23115835
TI  - 5 lessons learned.

PMID- 23115836
TI  - Hometown heroes.

PMID- 23115837
TI  - Online bill payment 2.0.

PMID- 23115838
TI  - Changing the odds of patient collections.

PMID- 23115839
TI  - What executives need to know about the audit world.

PMID- 23115840
TI  - Improving care coordination.

PMID- 23115841
TI  - One size does not fit all.

PMID- 23115842
TI  - 7 steps to MU success.

PMID- 23115843
TI  - [Image of the month. Infectious ulcer after a dog bite].

PMID- 23115844
TI  - [Clinical case of the month. Acute post-traumatic panophthalmitis].
AB  - Panophtalmitis is an intra-ocular and intra-orbital rare infection, but its
      consequences are often horrendous, with loss of both function and anatomy of the
      eye. The surgical approach and the antibiotherapy should be given as soon as
      possible, both by intra-vitreal and intra-venous injections. We report the case
      of a 49-year-old man who developed a Bacillus cereus panophtalmitis. A delay in
      the diagnosis lead to the loss of vision and the evisceration of the sick eye.
      Bacillus cereus panopthalmitis should be suspected in all cases of post-traumatic
      endophtalmitis with a soiled metallic foreign body, in patients with important
      local inflammatory signs as well as systemic signs. Vitrectomy, surgical
      extraction of the foreign body, intra-vitreal and systemic antibiotherapies
      should be given as soon as possible, even before the results of the
      bacteriological analysis.

PMID- 23115845
TI  - [2011 European Society of Cardiology guidelines for the management of
      cardiovascular diseases during pregnancy. Part 1].
AB  - In this article, we describe the 2011 European guidelines on the management of
      cardiovascular diseases during pregnancy, with particular attention to the
      management of valvular heart disease and anticoagulation.We will also describe
      cardiologic conditions in which pregnancy is contraindicated and the preferred
      way of delivery.

PMID- 23115846
TI  - [Cutaneous malignant melanoma: one single disease ?].
AB  - For the media and the public at large, malignant melanoma is the most dreadful
      cancer of the skin. This statement is obvious. However, some nuances merit to be
      considered. The clinical presentations, histopathology and molecular genetics
      point to the fact that malignant melanoma is not a single monolithic pathological
      condition. Different types of melanomas are distinguished based on distinct
      origins and contrasted prognoses. The management and information for the patient
      should be handled individually.

PMID- 23115847
TI  - [Influence of body weight on the natural history of and the therapeutic
      approaches to type 1 diabetes].
AB  - Obesity, whose prevalence is increasing in industrialized countries, is
      recognized as a major risk factor for the development of type 2 diabetes. In
      contrast, the role of excess adiposity in the natural history of type 1 diabetes
      (T1DM) and its impact on therapeutic approaches are by far less known and most
      probably largely underestimated. The following items will be most particularly
      considered: 1) the accelerator role of obesity in the development of T1DM in
      young predisposed individuals; 2) the difficult diagnosis in presence of hybrid
      or double diabetes combining insulin secretory defect and insulin resistance; 3)
      the problem of managing both body weight and glucose control, especially in young
      females and adolescents; 4) the possible deleterious effects of intensive insulin
      therapy on body weight and some markers of the metabolic syndrome; 5) the worse
      cardiovascular prognosis of T1DM patients when obesity is present; 6) the
      possible role of other medications as adjunct therapy to insulin in insulin
      resistant obese T1DM patients; and finally 7) the expected benefit of bariatric
      surgery in some well selected T1DM patients with severe obesity.

PMID- 23115848
TI  - [Endovascular treatment of descending aortic dissection (type B)].
AB  - Aortic dissection is one of the most serious aortic diseases by its potential for
      rupture, but also for other complications, such as cerebral or splanchnic
      ischemia, which may be fatal. If open surgery is the rule for lesions of the
      ascending aorta (type A), type B (not concerning the ascending aorta) is first a
      matter of medical treatment except when complications are present. In this case
      the placement of a stentgraft is a valuable alternative to open surgery. We
      report a patient presenting with a type B aortic dissection, characterized by
      rapid expansion and complicated by peri-aortic leakage, who was successfully
      treated by thoracic aortic stentgraft placement. This was done in a hybrid
      operating room associating the characteristics of a classical operating room for
      cardio-vascular surgery with those of an interventional radiology suite.

PMID- 23115849
TI  - [Rhupus: when rheumatoid arthritis meets lupus].
AB  - There exists diseases in rheumatology fulfilling classification criteria for
      either rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). They are
      called "rhupus". We retrospectively analyzed the data base "GLIMS" of the CHU de
      Liege from the starting date of november 2005 until april 2011 to identified
      those patients that were positive for the anti-sDNA antibody marker of SLE and
      for the anti-CCP antibody, marker of RA. Fourteen patients were identified and
      two other patients were added, one suffering from SLE, and the other from RA, and
      likely to be rhupus. Of the 16 patients analyzed, 9 were real RA with anti-dsDNA
      antibodies induced by anti-TNF-alpha therapies. Seven were candidates to be
      rhupus and 6 were retained. They were all women, with a median age of 51 years
      and in addition were all anti-SS-A antibody positive.

PMID- 23115850
TI  - [Medication of the month. Ticagrelor (Brilique): potent oral antagonist of
      platelet activity].
AB  - Dual antiplatelet therapy with clopidogrel combined with aspirin reduces ischemic
      events in acute coronary syndromes (ACS). The individual response to clopidogrel
      is, however, very variable from one subject to another, and the risk of events
      seems higher when platelet inhibition is insufficient. Ticagrelor is a potent
      oral inhibitor of platelet activity. It binds reversibly to the P2Y12 adenosine
      diphosphate. The platelet inhibition that it induces is faster and more
      pronounced than that of clopidogrel. In patients who have an ACS (PLATO study)
      with or without ST-segment elevation, treatment with ticagrelor as compared with
      clopidogrel significantly reduced the rate of death from vascular causes,
      myocardial infarction, or stroke, without an increase in the rate of overall
      major bleeding but with an increase in the rate of non-procedure-related
      bleeding. In Belgium, Brilique is currently indicated in combination with aspirin
      for the prevention of atherothrombotic events in patients with ACS.

PMID- 23115851
TI  - [Student diagnostic vignette. How to measure office blood pressure].
AB  - Routinely measuring blood pressure is still performed according to the
      auscultatory method using recognition of Korotkoff sounds. This usual technique
      is, however, often mishandled and is thus a source of error in the estimation of
      the true blood pressure level. Accuracy of such measure is, however, of paramount
      importance to be useful in daily medical practice. This methodology paper more
      specifically written for medical students recalls the essential principles of
      blood pressure measurement at the medical office, but also at home.

PMID- 23115852
TI  - Top standards compliance issues for first half of 2012.

PMID- 23115853
TI  - Accepted: Changes to requirements for deemed status ASCs.

PMID- 23115854
TI  - Accepted: New and revised requirements to align with CMS CoPs.

PMID- 23115855
TI  - Accepted: Changes to requirements for CA organizations performing CT scans.

PMID- 23115856
TI  - The Joint Commission launches new comprehensive stroke certification program.

PMID- 23115857
TI  - Approved: Revised behavioral health care requirements to eliminate redundancy.

PMID- 23115858
TI  - Mailed: Accreditation manual updates.

PMID- 23115859
TI  - Joint Commission to launch new intracycle monitoring process.

PMID- 23115860
TI  - Super suites.

PMID- 23115861
TI  - Professionalism and the power of words: a meditation.

PMID- 23115862
TI  - Truvada for HIV prophylaxis in heterosexual patients.

PMID- 23115863
TI  - A very firm, pearly nodule on the face.

PMID- 23115864
TI  - A day in the life.

PMID- 23115865
TI  - Respiratory tract infections: emerging viral pathogens.

PMID- 23115866
TI  - Vaccines in childhood: strategies to address the concerns of parents.

PMID- 23115867
TI  - Disseminated staphylococcal disease and sepsis in a 23-month-old child.

PMID- 23115868
TI  - Colonic ulceration in a patient with renal disease and hyperkalemia.

PMID- 23115869
TI  - Ankle sprains: treating to prevent the long-term consequences.

PMID- 23115870
TI  - Helping patients meet the challenge of complex regional pain syndrome.

PMID- 23115871
TI  - Roles and responsibilities of physician assistants practicing in Mohs surgery.
AB  - An estimated 30% of members of the American College of Mohs Surgery (ACMS) are
      using physician assistants (PAs). In Mohs surgery, the surgeon and the
      pathologist are the same person, so understanding which tasks are being delegated
      to PAs working in Mohs surgery is important. Our survey explores the number of
      PAs working with Mohs surgeons and the tasks delegated to PAs in this specialty.

PMID- 23115872
TI  - Where the Canadian physician assistants are in 2012.
AB  - Canada's physician assistant (PA) profession remains relatively unknown to the
      majority of Canadians, and the distribution of the approximately 300 Canadian PAs
      is uncertain. This report presents March 2012 findings from the 2011 Canadian PA
      survey, including the number of PAs employed and where they work.

PMID- 23115873
TI  - Faster-acting oral drug for ED.

PMID- 23115874
TI  - Fast-track areas in the emergency department: are they ethical?

PMID- 23115875
TI  - Unexpected consequences of rough play with friends.

PMID- 23115876
TI  - Ebb and flow: murmurings that are more than sweet nothings.

PMID- 23115877
TI  - Case of the month. Stress fracture lumbar spine.

PMID- 23115878
TI  - Intended and unintended births in the United States: 1982-2010.
AB  - OBJECTIVES: This report shows trends since 1982 in whether a woman wanted to get
      pregnant just before the pregnancy occurred. This is the most direct measure
      available of the extent to which women are able (or unable) to choose to have the
      number of births they want, when they want them. In this report, this is called
      the "standard measure of unintended pregnancy." METHODS: The data used in this
      report are primarily from the 2006-2010 National Survey of Family Growth (NSFG),
      conducted by the Centers for Disease Control and Prevention's National Center for
      Health Statistics. The 2006-2010 NSFG included in-person interviews with 12,279
      women aged 15-44. Some data in the trend analyses are taken from NSFG surveys
      conducted in 1982, 1988, 1995, and 2002. RESULTS: About 37% of births in the
      United States were unintended at the time of conception. The overall proportion
      unintended has not declined significantly since 1982. The proportion unintended
      did decline significantly between 1982 and 2006-2010 among births to married, non
      Hispanic white women. Large differences exist between groups in the percentage of
      births that are unintended. For example, unmarried women, black women, and women
      with less education or income are still much more likely to experience unintended
      births compared with married, white, college-educated, and high-income women.
      This report also describes some alternative measures of unintended births that
      give researchers an opportunity to study this topic in new ways.

PMID- 23115879
TI  - Looking forward. The development of hospital standards.

PMID- 23115880
TI  - Task shifting overcomes the limitations of volunteerism in developing nations.

PMID- 23115881
TI  - Using telemedicine to strengthen medical systems in limited-resource countries.

PMID- 23115882
TI  - ACS takes a stand on policies impacting the surgical workforce.

PMID- 23115883
TI  - Why the 2012 elections matter to you--the surgeon.

PMID- 23115884
TI  - Hospital Standardization Series. General hospitals of 100 or more beds. 1919.

PMID- 23115885
TI  - The Medicare EHR Incentive Program.

PMID- 23115887
TI  - The value of chapter membership: the rural surgeon's perspective.

PMID- 23115886
TI  - Governors' Committee on Socioeconomic Issues.

PMID- 23115888
TI  - The paradox of breast MRI: does finding occult disease make a difference?

PMID- 23115889
TI  - ASCs begin using wrong site surgery tool.

PMID- 23115890
TI  - Assaulted.

PMID- 23115891
TI  - A call to the field: complicated grief in the DSM-5.
AB  - While complicated grief has been addressed in part through some recommendations
      for modifications in the upcoming fifth version of the Diagnostic and Statistical
      Manual of Mental Disorders (DSM-5), there remain reasons for substantial concern
      about its scope therein and within clinical practice. The authors issue a call to
      the field, reiterating that complicated grief is complicated and cannot be
      confined to just one syndrome or disorder. Continued research is urged, and
      specific caveats are identified for exploring the complex dimensions of loss and
      grief. The authors advocate for ongoing dialogue about and investigation of
      various potential forms of complicated grief.

PMID- 23115892
TI  - Honoring patient care preferences: surrogates speak.
AB  - A growing body of evidence has pointed to the stressful experience surrounding
      surrogate decision-making on behalf of incapacitated patients. This study (N =
      59) asked surrogates to speak about their experiences immediately after having
      made a life-sustaining treatment decision. Grounded theory analysis revealed four
      themes: (1) the emotional impact of the decision-making process on the surrogate;
      (2) the difficulty of watching a loved one's health deteriorate; (3) the
      importance of having a Living Will (LW) or other written/verbal instructions; and
      (4) the reliance on spirituality as a means of coping with the surrogate
      experience. Findings of this study suggest that engaging surrogates at the time
      of patient admission may be essential in order to clarify patient preferences and
      strengthen communication between surrogates and the interdisciplinary healthcare
      team.

PMID- 23115893
TI  - Socio-economic transformation of Akan funeral rites in Ghana: the changing
      process.
AB  - Cultural traditions at the end of life solidify societal members. As the world
      becomes more globalized, socio-economic factors affect how traditional practices
      are expressed, and the role and toll they make on modern societies. This article
      examines the contemporary Akan funeral practices in Ghana. Akan lineage members,
      from birth through puberty, marriage, maturity, old age, go through various rites
      of passage that bond them culturally and spiritually to others in society. One
      such ritual is funeral celebration. Funeral celebration, an old practice, has
      always been at the heart of public social events of Akan people. However, the
      changes in Ghanaian Akan funerals over the past 4 decades, and their impact on
      the people, make this an important topic. The article describes the Akan belief
      of life after death, the respect accorded to the dead, the prestige associated
      with successful funeral celebrations, and socio-economic factors that continue to
      shape Akan funeral practices. Socio-economic impact and the resulting challenges
      are discussed.

PMID- 23115894
TI  - A psychological profile of a serial killer: a case report.
AB  - Serial killers have always fascinated society. A serial killer is typically
      defined as a perpetrator who murders three or more people over a period of time.
      Most reported cases of serial killers come from the United States and Canada. In
      India, there are few reported cases. We present, to the best of our knowledge,
      the first Indian case in the literature. The present case is of a 28-year-old
      man, Surinder Koli. The Department of Forensic Medicine & Toxicology, All India
      Institute of Medical Sciences, New Delphi handled the forensic study. We present
      a most unique psychological investigation into the mind of a serial killer.

PMID- 23115895
TI  - Accounts of suicidality in the Huntington disease community.
AB  - Health professionals, researchers, and philosophers have debated extensively
      about suicide. Some believe suicides result from mental pathology, whereas others
      argue that individuals are capable of rational suicide. This debate is
      particularly poignant within illness communities, where individuals may be
      suffering from chronic and incurable conditions. This article engages with these
      issues by presenting the accounts of 20 individuals with Huntington disease (HD),
      a fatal degenerative condition, and 10 informal caregivers (e.g., spouses).
      Suicide is a leading cause of death amongst people with HD, with an incidence
      rate many times higher than the general population. In contrast to the majority
      of the academic literature on HD suicidality, study participants did not connect
      suicide with mental pathology. Instead, they perceived suicide as a response to
      the realities of living with HD, such as prolonged physiological degeneration and
      the need for long-term intensive health care. These findings are subsequently
      discussed in relation to the rational-pathological suicide binary.

PMID- 23115896
TI  - Parental interest in a bereavement support visit when a child dies from cancer.
AB  - Parents who have experienced the death of a child from cancer have unique
      bereavement needs. This study evaluated the possibility of instituting a home
      based bereavement visit from the oncology team following a child's death. Parents
      completed a brief anonymous questionnaire measuring preferences regarding visit
      logistics and content. The majority (84%) of the 31 participants agreed that a
      home-based bereavement program is desirable. Qualitative analysis of parental
      comments revealed common themes including processing grief, practical suggestions
      for visit, recognition of individual differences, perceived risks and benefits of
      visit, connections with medical staff, and unmet needs for support. In
      conclusion, a home visit program may satisfy needs for additional support while
      alleviating barriers to other types of bereavement care.

PMID- 23115897
TI  - Building effective clinical teams in healthcare.
AB  - PURPOSE: This article aims to review teamwork and the creation of effective teams
      within healthcare. DESIGN/METHODOLOGY/APPROACH: By combining research material
      found in management, psychology and health services research the article explores
      the drivers increasing the importance of teamwork, reviews the current knowledge
      base on how to build a team and focuses on some of the barriers to effective team
      performance. FINDINGS: The simultaneous inflation of healthcare costs and
      necessity to improve quality of care has generated a demand for novel solutions
      in policy, strategy, commissioning and provider organisations. A critical, but
      commonly undervalued means by which quality can be improved is through
      structured, formalised incentivisation and development of teams, and the ability
      of individuals to work collectively and in collaboration. Several factors appear
      to contribute to the development of successful teams, including effective
      communication, comprehensive decision making, safety awareness and the ability to
      resolve conflict. Not only is strong leadership important if teams are to
      function effectively but the concept and importance of followership is also
      vital. RESEARCH LIMITATIONS/IMPLICATIONS: Building effective clinical teams is
      difficult. The research in this area is currently limited, as is the authors'
      understanding of the different requirements faced by those working in different
      areas of the health and social care environment. ORIGINALITY/VALUE: This article
      provides a starting place for those interested in leading and developing teams of
      clinicians.

PMID- 23115898
TI  - Medical leadership and engagement: no longer an optional extra.
AB  - PURPOSE: The purpose of this paper is to analyse the factors that are leading
      many international health systems to seek new ways of getting doctors to be more
      engaged in management, leadership and service improvement.
      DESIGN/METHODOLOGY/APPROACH: The paper draws on the growing research and
      literature that is demonstrating a strong association between extent of medical
      engagement and clinical and organisational performance. The current NHS reforms
      in England place general practitioners very much at the centre of the
      commissioning process and increasingly consultant medical staff are leading the
      drive to improve access, quality, safety and new ways of delivering care within
      hospitals and across health systems. FINDINGS: In parallel with political and
      organisational change, the medical profession has been redefining the
      characteristics of a good doctor. This includes not only the reinforcement of the
      need for doctors to be clinical experts but also good managers and leaders. As
      the custodians of the processes and micro-systems of health care, doctors are
      ideally placed to lead improvements. The paper argues that there is perhaps
      congruence between politicians and policy makers for greater medical leadership
      and engagement with doctors becoming "shareholders" in the running of services,
      organisations and systems. ORIGINALITY/VALUE: The paper concludes that perhaps
      the era of strong general management may be replaced by one where non-clinical
      managers and clinicians work in partnership to optimise the different expertise,
      experience and values to achieve high quality, productive and patient-focused
      care.

PMID- 23115899
TI  - Redefining the school nurse role: an organizational perspective.
AB  - PURPOSE: This paper aims to identify organizational readiness for change towards
      adoption of a redefined role of the school nurse as a strategic option in the
      context of a health promoting school approach. This new role is consistent with
      planned change directed at life habits and life conditions.
      DESIGN/METHODOLOGY/APPROACH: A questionnaire based on a modified version of the
      organizational readiness for change (ORC) framework was e-mailed to 122 top and
      middle managers (response rate of 74 percent) in 42 local health organizations in
      the Province of Quebec, Canada, during the fall of 2009. FINDINGS: In total, 90
      percent of participants perceived the proposed role as a solution to fulfil their
      school health program needs, especially to plan and integrate health promotion
      projects. The lack of resources and nursing support emerged as factors hampering
      the capacity of school nurses to play such a role. RESEARCH
      LIMITATIONS/IMPLICATIONS: Additional implications of the ORC framework are needed
      in order to better address organizational readiness for complex changes in
      specific health-related settings. PRACTICAL IMPLICATIONS: Access to information
      technology and the development of computer skills would help enhance this
      encompassing role in health promotion. ORIGINALITY/VALUE: Findings have the
      potential to better inform health authorities regarding the new role of the
      school nurse as a strategic option in health promotion. This study also provides
      an application of the theoretical framework showing the need for additional
      empirical tests.

PMID- 23115900
TI  - Motivation and retention of health workers in Ghana's district hospitals:
      addressing the critical issues.
AB  - PURPOSE: This study seeks to undertake a systematic review to consolidate
      existing empirical evidence on the impact of financial and non-financial
      incentives on motivation and retention of health workers in Ghana's district
      hospitals. DESIGN/METHODOLOGY/APPROACH: The study employed a purely quantitative
      design with a sample of 285 health workers from ten district hospitals in four
      regions of Ghana. A stepwise regression model was used in the analysis. FINDINGS:
      The study found that financial incentives significantly influence motivation and
      intention to remain in the district hospital. Further, of the four factor model
      of the non-financial incentives, only three (leadership skill and supervision,
      opportunities for continuing professional development and availability of
      infrastructure and resources) were predictors of motivation and retention.
      RESEARCH LIMITATIONS/IMPLICATIONS: A major limitation of the study is that the
      sample of health workers was biased towards nurses (n = 160; 56.1 percent). This
      is explained by their large presence in remote districts in Ghana. A qualitative
      approach could enrich the findings by bringing out the many complex views of
      health workers regarding issues of motivation and retention, since quantitative
      studies are better applied to establish causal relationships. ORIGINALITY/VALUE:
      The findings suggest that appropriate legislations backing salary supplements,
      commitment-based bonus payments with a set of internal regulations and leadership
      with sound managerial qualities are required to pursue workforce retention in
      district hospitals.

PMID- 23115901
TI  - Managing clinical integration: a comparative case study in a merged university
      hospital.
AB  - PURPOSE: This paper seeks to explore critical factors that may obstruct or
      advance integration efforts initiated by the clinical management following a
      hospital merger. The aim is to increase the understanding of why clinical
      integration succeeds or fails. DESIGN/METHODOLOGY/APPROACH: The authors compare
      two cases of clinical integration efforts following the Karolinska University
      Hospital merger in Sweden. Each case represents two merged clinical departments
      of the same specialty from each hospital site. In total, 53 interviews were
      conducted with individuals representing various staff categories and documents
      were collected to check data consistency. FINDINGS: The study identifies three
      critical factors that seem to be instrumental for the process and outcome of
      integration efforts and these are clinical management's interpretation of the
      mandate; design of the management constellation; and approach to integration.
      Obstructive factors are: a sole focus on the formal assignment from the top;
      individual leadership; and the use of a classic, planned, top-down management
      approach. Supportive factors are: paying attention to multiple stakeholders;
      shared leadership; and the use of an emergent, bottom-up management approach
      within planned boundaries. These findings are basically consistent with the
      literature's prescriptions for managing professional organisations. PRACTICAL
      IMPLICATIONS: Managers need to understand that public healthcare organisations
      are based on competing institutional logics that need to be handled in a balanced
      way if clinical integration is to be achieved--especially the tension between
      managerialism and professionalism. ORIGINALITY/VALUE: By focusing on the merger
      consequences for clinical units, this paper addresses an important gap in the
      healthcare merger literature.

PMID- 23115902
TI  - Trends in telemedicine assessment indicate neglect of key criteria for predicting
      success.
AB  - PURPOSE: This innovative analysis aims to quantify the use of evaluation criteria
      in telemedicine and to identify current trends in metric adoption. The focus is
      to determine the frequency of actual performance metric reporting in telemedicine
      evaluation, in contrast to systematic reviews where assessment of study quality
      is the goal. DESIGN/METHODOLOGY/APPROACH: Automated literature search identified
      telemedicine studies reporting quantitative performance metrics. Studies were
      classified by telemedicine class; store-and-forward (SAF), real-time consultation
      (RTC) and telecare (TC), and study stage. Studies were scanned for evaluation
      metric reporting, i.e. clinical outcomes, satisfaction, patient quality and cost
      measures. FINDINGS: Evaluation metric use was compared among telemedicine
      classes, and between pilot and routine use stages. Diagnostic accuracy was
      reported significantly more frequently in pilots for RTC and TC. Cost measures
      were more frequently reported in routine use for TC. Clinical effectiveness and
      hospital attendance were better reported in routine use for SAF. Comparison also
      revealed different evaluation strategies. In pilots, SAF favoured diagnostic
      accuracy, compared to RTC and TC. TC preferred clinical effectiveness evaluations
      and TC more frequently assessed patient satisfaction. Cost was only reported in
      less than 20 per cent of studies, but most frequently in RTC. Routine use led to
      increased reporting of all metrics, except diagnostic accuracy. Clinical
      effectiveness reporting increased significantly with routine use for RTC and SAF,
      but declined for TC. ORIGINALITY/VALUE: Clinical outcomes and patient
      satisfaction were reported frequently in telemedicine studies, but reporting of
      other performance metrics was rare. Understanding current trends in metric
      reporting will facilitate better design of future telemedicine evaluations.

PMID- 23115903
TI  - Managerialism and professional strategies: a case from nurses in Portugal.
AB  - PURPOSE: There have been profound changes in the Portuguese national health
      system (NHS), instigated under the influence of managerialism and the new public
      management (NPM) "philosophy". These changes have been in line with what has
      happened in other developed countries. At the beginning of the new century,
      important reforms that emphasised the efficient use of scarce resources were
      implemented. The objective of this study is to understand how nurses are adapting
      to a more managerial environment, one in which economic rationalism and market
      driven initiatives are the key principles behind the health reforms.
      DESIGN/METHODOLOGY/APPROACH: A qualitative study was developed, based on semi
      structured interviews with 83 nurses with managerial duties in ten hospitals in
      Portugal. All interviews were tape-recorded and each interviewee's discourses
      were subjected to content analysis. FINDINGS: Data analysis led to the conclusion
      that under the new logic of the market and managerialism, these professionals
      have tried to (re)define their professionalisation route by emphasising the
      importance of care but also by trying to incorporate management as their dominant
      role in the social division of work. In reconfiguring their notion of
      professionalism, nurses were incorporating new practices in their day-to-day
      activities. This empirical study confirms that professionalism can also be
      conceptualised as a technology of self-control being able to discipline
      professionals at the micro level. ORIGINALITY/VALUE: This research is an
      empirical study based on the effects of managerialism on nurses with managerial
      duties in Portugal. This study contributes to a better understanding of the
      complex process of the professionalisation of nurses in a context of
      institutional change.

PMID- 23115904
TI  - Knowledge structures of a health ecosystem.
AB  - PURPOSE: This paper aims to hypothesize that modern health systems are
      transforming towards what has been called a health ecosystem in complexity-based
      health care literature. It has been argued that complexity arises from the
      interconnectedness, which in this paper is equated with knowledge flows between
      actors. The paper seeks to discuss the possible implications of a health
      ecosystem approach to health system management. DESIGN/METHODOLOGY/APPROACH: The
      paper is conceptual in nature but the transition towards a health ecosystem is
      illustrated with an example of a regional health care system in Finland. The case
      description and related analysis presented are based on qualitative data gathered
      by interviewing leading office-holders, by process modeling and by observing
      management group meetings. FINDINGS: Conceptually, a health ecosystem seems to
      have potential for the system-level analysis of the health care system. The
      discussion concludes that management of knowledge flows should be a strategic
      management function for individual health organizations as well as for the wider
      health system. RESEARCH LIMITATIONS/IMPLICATIONS: This study focuses on a Finnish
      health care system. The operations and structures of health care services and
      systems vary in different areas and countries. PRACTICAL IMPLICATIONS: The
      practical illustration of the health ecosystem provides a reminder that health
      care systems are dynamic and largely based on interaction between different
      actors. The approach provides new strategic insights for the development of
      health care systems by concentrating on interrelationships and knowledge flows.
      ORIGINALITY/VALUE: The literature has suggested that the ecosystem metaphor
      offers useful insights for the development of health care systems. Nevertheless,
      this approach has not been thoroughly studied so far. This paper makes a
      contribution by presenting a practical illustration of the framework and in light
      of this discusses the possible implications for health care management.

PMID- 23115905
TI  - The impact of team empowerment on proactivity: the moderating roles of leader's
      emotional intelligence and proactive personality.
AB  - PURPOSE: The purpose of this study is to investigate the relationship between
      team empowerment and team proactivity and the moderating roles of a team leader's
      emotional intelligence (EI) and a team member's proactive personality.
      DESIGN/METHODOLOGY/APPROACH: To provide a rigorous test of the hypotheses, a
      field study from a sample of 910 certified nurses in 82 teams from 12 university
      hospitals in Turkey was conducted. FINDINGS: The results reveal that proactivity
      is positively associated with team empowerment. In addition, team leader's EI and
      team members' proactive personality influence the relationship between team
      empowerment and team proactivity. Specifically, teams exhibit the highest
      proactivity when team leaders' EI and team members' proactive personality are
      high. RESEARCH LIMITATIONS/IMPLICATIONS: The main strength of the investigation
      in this study was its multilevel research design. Most research on proactivity
      and empowerment has been conducted within single organizations, precluding an
      assessment of the way in which individual difference variables influence
      empowerment or proactivity. The multilevel design incorporated in this study,
      however, was capable of capturing the complexity of individual behaviors by
      considering different contexts. PRACTICAL IMPLICATIONS: In encouraging team
      proactivity, leadership and team members' personality characteristics do matter.
      Identifying individual difference variables such as team leader's EI, leader
      member exchange, locus of control or team members' personality help to advance
      the theoretical understanding of the team proactivity. This study provides
      evidence of the positive relationship between team empowerment and team
      proactivity. Such knowledge may help to search for continuous improvement and
      innovative solutions to work problems employed by healthcare administrators and
      potentially reduce the costs associated with losing high-potential nurses.
      ORIGINALITY/VALUE: This is one of the first studies to provide evidence of the
      moderating roles of the team leader's EI and team members' proactive personality
      levels on the relationship between team empowerment and team proactivity in
      university hospitals that formally implement work teams.

PMID- 23115906
TI  - Leadership, clinician managers and a thing called "hybridity".
AB  - PURPOSE: In many countries leadership theories and leadership development
      programs in healthcare have been dominated by individualistic and heroic
      approaches that focus on developing the skills and competencies of health
      professionals. Alternative approaches have been proffered but mainly in the form
      of post-heroic and distributed forms of leadership. The notion of "hybridity" has
      emerged to challenge the assumptions of distributed leadership. The paper seeks
      to explore how the concept of hybridity can be used to re-theorize leadership in
      healthcare as it relates to clinician managers (or hybrid-professional managers).
      DESIGN/METHODOLOGY/APPROACH: The theoretical developments are explored and
      empirical material is presented from research in Australian public hospitals to
      support the case for the existence of hybridized forms of leadership in
      healthcare. The paper discusses whether hybridity needs re-theorizing to
      adequately account for clinician leadership. It contributes to debates
      surrounding the role of clinician leadership in healthcare reform particularly in
      relation to those doctors who occupy management positions at the division or unit
      levels as distinct to CEOs. The study uses qualitative research, i.e. interactive
      interviews to present accounts of how healthcare professionals describe
      leadership. It undertakes both deductive and inductive theme analysis of the
      interview material. FINDINGS: There is support for hybridized configurations of
      leadership in interview materials of healthcare professionals but other aspects
      were also noted that cannot be explained by this approach alone.
      ORIGINALITY/VALUE: The paper is the first to examine the concept of hybridity in
      the context of clinician leadership. Many approaches to leadership in healthcare
      fail to address the complexity of leadership within the ranks of clinician
      managers and thus are unable to deal adequately with the role of leadership in
      healthcare reform and change.

PMID- 23115907
TI  - Members' sensemaking in a multi-professional team.
AB  - PURPOSE: The aim of this study is to investigate sensemaking as interaction among
      team members in a multi-professional team setting in a new public management
      context at a Swedish Child and Youth Psychiatric Unit.
      DESIGN/METHODOLOGY/APPROACH: A discursive pragmatic approach grounded in
      ethonomethodology is taken in the analysis of a treatment conference (TC). In
      order to interpret and understand the multi-voiced complexity of discourse and of
      talk-in-interaction, the authors use dialogism in the analysis of the members'
      sensemaking processes. The analysis is based on the theoretical assumption that
      language and texts are the primary tools actors use to comprehend the social
      reality and to make sense of their multi-professional discussions. Health care
      managers are offered insights, derived from theory and empirical evidence, into
      how professionals' communications influence multi-professional cooperation. The
      team leader and members are interviewed before and after the observed TC.
      FINDINGS: Team members create their identities and positions in the group by
      interpreting and "misinterpreting" talk-in-interaction. The analyses reveal the
      ways the team members relate to their treatment methods in the discussion of a
      patient; advocating a treatment method means that the team member and the method
      are intertwined. PRACTICAL IMPLICATIONS: The findings may be valuable to health
      care professionals and managers working in teams by showing them how to achieve
      greater cooperation through the use of verbal abilities. ORIGINALITY/VALUE: The
      findings and methods contribute to the international research on cooperation
      problems in multi-professional teams and to the empirical research on
      institutional discourse through text and talk.

PMID- 23115908
TI  - Clinical managers in the primary care sector: do the benefits stack up?
AB  - PURPOSE: The purpose of this paper is to explore the nature and value of the
      clinical management role undertaken by primary care doctors in Ireland. To date,
      a majority of research has focused on clinical management roles in the acute
      sector. DESIGN/METHODOLOGY/APPROACH: The paper presents a sub-set of data from a
      mixed methods study. In total, 14 semi-structured interviews are drawn upon to
      identify the nature and value of the clinical management role in primary care.
      FINDINGS: Comparison with acute sector research identifies considerable
      differences in the nature of the clinical management role across sectors--and in
      the associated value proposition. Structural and role-related contingencies
      affecting the potential value of clinical management roles in Irish primary care
      are discussed. Structural influences include the private ownership structure, low
      complexity and limited requirement for cross-professional coordination. Role
      related influences include the primacy of the clinical identity, time constraints
      and lack of managerial training. RESEARCH LIMITATIONS/IMPLICATIONS: The findings
      provide a limited basis for generalisation, premised on 14 interviews in one
      national context. However, given the international shift towards the provision of
      health services in primary care, they provide a research agenda for an important
      healthcare context. PRACTICAL IMPLICATIONS: The findings draw attention to the
      need for policy consideration of the value of the clinical manager role in
      primary care; how policy can support effective primary care management; and the
      need for specialised management training, which takes account of the small-firm
      context. ORIGINALITY/VALUE: The paper identifies that primary-care clinical
      management roles focus on operational management and oversight and discusses the
      structural and role-related factors which affect their efficacy.

PMID- 23115909
TI  - Strategic groups and outcomes in the US hospice care industry.
AB  - PURPOSE: As a result of a drastic increase in new patients, two major shifts are
      occurring in the US hospice care industry: an increase in the number of for
      profit providers, and hospices are increasing in size through acquisitions and
      mergers. Hospices are trying to both increase the number of innovative programs
      they offer and decrease their operating expenses to improve their margins and
      attract more patients. This study seeks to investigate if strategic groups exist
      within the industry as hospices try to become more innovative and efficient,
      which grouping factors are most significant, and to determine whether there is a
      relationship between group membership and performance.
      DESIGN/METHODOLOGY/APPROACH: Cluster analysis and ANOVA are used to analyze data
      from 93 California hospices. FINDINGS: Three strategic groups exist within the
      market, innovative practices significantly affect group membership, and
      innovation-oriented groups outperform others in terms of quality of care.
      PRACTICAL IMPLICATIONS: Many hospices focus on innovation, and evidence suggests
      that continued pursuit of innovative practices is critical, whereas efficiency
      does not appear to have a significant impact on quality of care. Focus on such
      evidence-based practices is important for long-term success. ORIGINALITY/VALUE:
      This is the first study to investigate strategic group formation in the hospice
      care industry.

PMID- 23115910
TI  - Using evaluation theory in priority setting and resource allocation.
AB  - PURPOSE: Public sector interest in methods for priority setting and program or
      policy evaluation has grown considerably over the last several decades, given
      increased expectations for accountable and efficient use of resources and
      emphasis on evidence-based decision making as a component of good management
      practice. While there has been some occasional effort to conduct evaluation of
      priority setting projects, the literatures around priority setting and evaluation
      have largely evolved separately. In this paper, the aim is to bring them
      together. DESIGN/METHODOLOGY/APPROACH: The contention is that evaluation theory
      is a means by which evaluators reflect upon what it is they are doing when they
      do evaluation work. Theories help to organize thinking, sort out relevant from
      irrelevant information, provide transparent grounds for particular implementation
      choices, and can help resolve problematic issues which may arise in the conduct
      of an evaluation project. FINDINGS: A detailed review of three major branches of
      evaluation theory--methods, utilization, and valuing--identifies how such
      theories can guide the development of efforts to evaluate priority setting and
      resource allocation initiatives. Evaluation theories differ in terms of their
      guiding question, anticipated setting or context, evaluation foci, perspective
      from which benefits are calculated, and typical methods endorsed.
      ORIGINALITY/VALUE: Choosing a particular theoretical approach will structure the
      way in which any priority setting process is evaluated. The paper suggests that
      explicitly considering evaluation theory makes key aspects of the evaluation
      process more visible to all stakeholders, and can assist in the design of
      effective evaluation of priority setting processes; this should iteratively serve
      to improve the understanding of priority setting practices themselves.

PMID- 23115911
TI  - Social resources and change in functional health: comparing three age groups.
AB  - This study examined the mediating and moderating role of social resources on the
      association between age and change in functional health for three age groups of
      older adults. Data were provided by those in their 60s, 80s, and 100s who
      participated in the first two phases of the Georgia Centenarian study. Analyses
      confirmed the study's hypothesis that social resources moderated the relationship
      between age group and change in functional health; in particular, centenarians
      who experienced the greatest decline in IADLs scored the highest on social
      resources at time 1. No evidence was found for mediation by social resources or a
      directional influence by either level of social resources or functional health on
      change in the other resource. Evidence from this study challenges researchers and
      service providers to consider the heterogeneity in resources among older adults.

PMID- 23115912
TI  - A cross-cultural examination of the positivity effect in memory: United States
      vs. China.
AB  - Many studies conducted in the United States (U.S.) have documented a positivity
      effect in aging-a tendency for older adults to remember more positive than
      negative information in comparison to young adults. Despite this cognitive
      emotional benefit, U.S. adults still hold a more negative view of aging compared
      to adults in Asia. We hypothesized that these aging stereotypes may contribute to
      different patterns of age-related emotional memory processing in the two
      cultures. In the present study, we tested young and older adults in the U.S. and
      China on a View of Aging task and an emotional picture memory task. Chinese older
      adults hold a significantly more positive view of aging compared to all other
      groups of participants. Older adults in both countries demonstrated an age
      related positivity effect, but Chinese older adults showed a trend in remembering
      fewer negative pictures than their American counterparts. These findings suggest
      that aging stereotypes might significantly influence older adults' cognitive
      abilities.

PMID- 23115913
TI  - Gender differences in how retirees perceive factors influencing unretirement.
AB  - Returning to paid employment after retirement is occurring in many developed
      countries and can be expected to increase in the future. This study compared how
      women (n = 202) and men (n = 347) who had retired from a managerial or
      professional career occupation perceived factors associated with unretirement.
      Retired professional women perceived reasons to unretire, age-friendly human
      resource practices, and re-entry barriers to have greater influence on retirees'
      decision to unretire than retired managerial women and retired men. Both groups
      of retired women perceived training and development opportunities to have more
      influence than retired men. A major contribution of this study is the
      identification of pre-retirement career occupation as having an important effect
      on how female, but not male, retirees perceived the various factors. The findings
      suggest that researchers and employers need to consider the diversity that exists
      among retirees, not only gender differences but also differences among retired
      career women.

PMID- 23115915
TI  - [Having all the tools for our return].

PMID- 23115914
TI  - Social-relational risk factors for predicting elder physical abuse: an ecological
      bi-focal model.
AB  - Annually in the United States, 1 to 5 million older adults, 65 and above, are
      physically or sexually injured or mistreated by their caregivers in family
      settings. This study examined the prevalence and risk factors involved in elder
      physical abuse by adult child caregivers, moving from the immediate elderly
      parent/adult child relationship context to more distal social support contexts,
      utilizing a subsample of 203 elderly participants from the Midlife Development in
      the United States study (MIDUS II, 2004-2006). LISREL modeling examined causal
      pathways between elderly demographic characteristics, physical/emotional health,
      and behavioral and contextual characteristics from an ecological perspective.
      Data modeling was accomplished using Mplus, PAXW, and SYSTAT statistical software
      packages. Results indicate that latent factors including older adult health,
      social isolation of the older adult, and adult child characteristics were
      significantly associated with elder physical abuse, as mediated by the quality of
      the elderly parent/adult child relationship.

PMID- 23115916
TI  - [General Assembly of the Kidney].

PMID- 23115917
TI  - [The French do not take care of themselves as much as they think].

PMID- 23115918
TI  - [High-tech blood glucose self-monitoring].

PMID- 23115920
TI  - [Competency-based nursing training].
AB  - The application of the new nursing training reference framework requires the
      active participation of professionals in the field, notably with assessing
      students' skills during a work placement. The skills approach represents a
      paradigm shift for caregivers, one which requires reflection with regard to their
      activities, and the creation of tools suitable for constructive assessment. A
      task force within the Toulouse cancer unit has been created to reflect on and
      support the changes brought about by the reform.

PMID- 23115919
TI  - [The psychiatric liaison nurse in somatic care departments].
AB  - The role of the psychiatric liaison nurse is continuing to develop within somatic
      wards. Its foundations are based on the recognition of the value accorded to
      interactions between physical and psychical dimension. This account of a
      psychiatric liaison nurse's practice at the university hospital of Nantes shows
      the positive impact a successful collaboration on inpatients.

PMID- 23115921
TI  - [Skin necrosis resulting from the extravasation of intravenous injections].
AB  - Extravasation is the diffusion of a product injected intravenously into the
      perivascular or subcutaneous spaces. Skin necrosis of iatrogenic origin can be
      observed for example with a subcutaneous perfusion of solution containing
      potassium chloride or the extravasation of 30% hypertonic glucose serum. Whenever
      a product is injected, the administration route for which the product has
      obtained marketing authorisation must be respected and a perfusion time of at
      least 4 to 5 hours per litre of solution perfused must be observed.

PMID- 23115922
TI  - [Osteoarthritis. A public health problem].

PMID- 23115923
TI  - [Osteoarthritis epidemiology and risk factors].
AB  - Osteoarthritis is the world's most widespread rheumatic disease. It mainly
      affects people aged over 65. The elderly, women, obese people and those with
      previous injuries are most at risk from osteoarthritis.

PMID- 23115924
TI  - [Osteoarthritis, a painful and crippling illness].
AB  - All joint tissues are affected by the pathological process which leads to
      osteoarthritis: cartilage, subchrondal bone and synovial membrane. The speed at
      which osteoarthritis symptoms develop depends on the patient. There is currently
      no way of knowing how the disease will develop in a patient.

PMID- 23115925
TI  - [Medical treatment of osteoarthritis in the knees and hips].
AB  - Treatment for osteoarthritis not only involves prescribing painkillers and anti
      inflammatory drugs; it also involves having a healthy lifestyle such as losing
      weight and keeping active. These solutions protect the joints and avoid
      stiffness.

PMID- 23115926
TI  - [Prostheses, a surgical answer to the wear and tear of joints due to
      osteoarthritis].
AB  - The joints of patients with osteoarthritis suffer constant and irreversible wear
      and tear resulting in pain and functional incapacity. Prostheses are an
      appropriate response for improving quality of life.

PMID- 23115927
TI  - [Nursing care of osteoarthritic patients who require a prosthesis].
AB  - Nursing patients undergoing an operation for a prosthetic due to osteoarthritis
      requires the nurse to be attentive during postoperative surveillance. The nurse
      must provide preventative and educational care to facilitate the patient's return
      home.

PMID- 23115928
TI  - [Chronic osteoarthritis home care].
AB  - Osteoarthritis is a constantly evolving disease. It is a real public health
      issue. It is therefore important to re-examine the disease and prevent it so that
      it doesn't affect sufferers' day-to-day lives.

PMID- 23115929
TI  - [Athletes with osteoarthritis: assessment and care].
AB  - Osteoarthritis in athletes requires assessment and accurate identification of the
      patient's risk factors. The aim is to offer the patients the right therapy for
      them so that they can continue practising their sport.

PMID- 23115930
TI  - [The advantages of using a clinical nurse specialist for osteoarthritis].

PMID- 23115931
TI  - [Balneotherapy and osteoarthritis treatment].
AB  - Balneotherapy is a complementary form of medicine which uses natural thermal
      mineral resources in situ. It provides patients with osteoarthritis with a full
      treatment to ease pain and improve functions in the long-term without causing any
      significant therapeutic risks.

PMID- 23115932
TI  - [The journey of the rheumatoid arthritis patient].

PMID- 23115933
TI  - [Lumbar spine arthritis at age 40, a daily battle. Remarks collected by Florence
      Michon].

PMID- 23115934
TI  - [Osteoarthritis and self-esteem].
AB  - Osteoarthritis is a pathology which forces patients who suffer from it to deal
      with their illness and to endure it by living differently. The nurse therefore
      plays a major role in supporting these patients in order to help them regain
      their self-esteem.

PMID- 23115935
TI  - [Patient education for osteoarthritis].

PMID- 23115936
TI  - [Bibliography. Osteoarthritis].

PMID- 23115937
TI  - [Quantitative methodology and simple descriptive studies].
AB  - Quantitative methodologies are frequently used in nursing research.The
      descriptive study is an approach which is particularly appropriate when a theme
      has not been extensively explored by scientific works. This type of study opens
      up the way for research work aiming to explore the subject in greater depth.

PMID- 23115938
TI  - [Planning and coordination of patient education].

PMID- 23115939
TI  - [A study for candidemia during the six year period from 1993 to 1999 in St.
      Luke's International Hospital].
AB  - There were 71 patients with candidemia in our hospital from November 1, 1993 to
      October 31, 1999. We investigated the 59 patients from isolated species, route of
      infection, underlying disorders, risk factors, complications, treatment and
      prognosis.Candida albicans was the most commonly isolated species (52%), followed
      by Candida tropicalis (11%). Eighty eight percent of the patients developed
      candidemia from central venous catheter related infections. The risk factors to
      candidemia included keeping the catheter in place for more than 5 days,
      gastrointestinal tract malignancies, postoperative state of gastrointestinal
      tract surgery, administration of broad-spectrum or combination antibiotics for
      more than 5 days, and under corticosteroid therapy. About half of the patients
      (47%) had complications, including endophthalmitis (19 patients, 32%), septic
      shock (12 patients, 20 %). Mortality rate associated with candidemia was 46%.
      Mortality rate was lower in 20 patients who were treated with amphotericin B
      (40%) than in 34 patients treated with only fluconazole (50%), but it was not
      statistically significant. In order to make an early diagnosis of candidemia,
      taking blood cultures and ophthalmologic examinations are essential, especially
      for patients who have those risk factors to candidemia mentioned above. If the
      patient was suspected of having catheter related infection, the catheter should
      be removed quickly and the catheter tip should be cultured. Once candidemia is
      found, ophthalmologic examination and systemic antifungal therapy are needed.
      Antifungal therapy with Amphotericin B should be used for patients with severe
      candidemia or with candide-

PMID- 23115940
TI  - [Isolation rate and susceptibilities of candida species from blood, vascular
      catheter, urine and stool].
AB  - We evaluated species distribution and antifungal susceptibility of Candida
      isolates during 2002-2008. Of 177 Candida isolates from blood, species
      distribution was 90 (51%) Candida albicans, 30 (17%) C. parapsilosis, 22 (12%) C.
      glabrata, 6 (3%) C. tropicalis and 29 (16%) other Candida spp.. Of 162 Candida
      isolates from vascular catheter, species distribution was 87 (54%) C. albicans,
      14 (9%) C. parapsilosis, 36 (22%) C. glabrata, 5 (3%), C. tropicalis, 2 (1%) C.
      krusei and 18 (11%) other Candida spp.. Of 1889 Candida isolates from urine,
      species distribution was 1165 (62%) C. albicans, 22 (1%) C. parapsilosis, 484
      (26%) C. glabrata, 83 (4%) C. tropicalis, 26 (1%) C. krusei and 109 (6%) other
      Candida spp.. Of 782 Candida isolates from stool, species distribution was 425
      (54%) C. albicans, 3 (1%) C. parapsilosis, 103 (13%) C. glabrata, 28 (4%) C.
      tropicalis, 5 (1%), C. krusei and 218 (28%) other Candida spp. Both C. albicans
      and non-Candida spp. isolated from urine increased slightly over the past 7
      years. Flucytosine, fluconazole, itraconazole and micafungin still have strong
      activity against Candida isolates.

PMID- 23115941
TI  - A surveillance of high-level gentamicin-resistant enterococcal bacteremia.
AB  - Enterococci have recently been recognized as a causative organism of intractable
      infections, including severe sepsis and infective endocarditis, in
      immunocompromised patients. This study investigated the epidemiological,
      microbiological, and prognostic characteristics of high-level gentamicin
      resistant (HLGR) enterococcal bacteremia, including severe cases of infective
      endocarditis, in Japan. A total of 155 enterococcal bacteremia episodes were
      identified between July 2007 and December 2009. HLGR strains accounted for 28% of
      all enterococcal strains: HLGR Enterococcus faecalis/Enterococcus faecium strains
      accounted for 32%/24%. The 30-day mortality rate was 31%. There was no
      significant difference in the 30-day mortality rates between HLGR and non-HLGR
      enterococcal bacteremia. There were two cases of HLGR enterococcal endocarditis,
      which were successfully treated with ampicillin plus ceftriaxone. We consider it
      important to examine the presence or absence of HLGR strains in all cases of
      intractable enterococcal infection, especially infective endocarditis.

PMID- 23115942
TI  - Acute polyradiculoneuritis syndrome: clinical observations and differential
      diagnosis.
AB  - Guillain-Barre syndrome (GBS) and neuroborreliosis may clinically manifest with
      symptoms related to acute polyradiculoneuritis. The aim and purpose of this study
      was analysis of clinical picture in patients with acute polyradiculoneuritis and
      their differential diagnosis into patients with GBS or meningoradiculoneuritis
      within the framework of neuroborreliosis. In this retrospective study, medical
      records of patients with acute polyradiculoneuritis hospitalized at University
      Department of Neurology, Sestre milosrdnice University Hospital Center during a 4
      year period were analyzed. The study included data on 27 patients. Definitive
      diagnosis ofGBS was made in 23 patients and of neuroborreliosis in four (14.8%)
      patients. Acute inflammatory demyelinating polyneuropathy was recorded in 69% of
      GBS patients, Miller Fisher syndrome in four patients, and acute motor axonal
      neuropathy and/or acute motor and sensory axonal neuropathy in three patients.
      Clinically, patients with neuroborreliosis manifested flaccid tetraparesis,
      peripheral facial nerve paresis, bulbar paresis, ocular motility disorders, and
      sensory symptoms of radicular pain and paresthesias. Considering the relatively
      high prevalence of neuroborreliosis in north-west Croatia, it is important to
      exclude meningoradiculoneuritis caused by Borrelia burgdorferi on differential
      diagnosis of GBS in these patients.

PMID- 23115943
TI  - Carcinoma in situ of urinary bladder: incidence, treatment and clinical outcomes
      during ten-year follow-up.
AB  - Bladder carcinoma in situ (CIS) is a rare, high-grade intraepithelial neoplasm
      with a high tendency of progression and unpredictable clinical course. The aim of
      this study was to evaluate the incidence, treatment and clinical outcome of
      patients with CIS during a 10-year period. Medical records of 1062 patients with
      primary bladder cancer and 847 patients with recurrent bladder cancer that
      underwent tumor resection at Department of Urology, Split University Hospital
      Center, Split, Croatia, between January 2001 and December 2010, were analyzed.
      Among all treated patients with primary bladder neoplasms, 51 (4.8%) had CIS.
      Primary CIS was diagnosed in 18 (1.7%) and concomitant CIS in 33 (3.1%) patients.
      In the same period, 847 patients with recurrent tumors were treated by
      transurethral resection (TUR), 12 (1.4%) of them with secondary CIS. Clinical
      course was followed-up in 15 patients with primary CIS and 21 patients with
      concomitant (TaT1) CIS. BCG immunotherapy was applied in 12 patients with primary
      and 17 patients with concomitant CIS. After median follow-up of 50 months, 9
      patients with primary CIS had no sign of disease, 4 progressed, 1 had recurrence
      and 1 died. After median follow-up of 37 months, 13 (62%) patients with
      concomitant CIS had complete response, 3 progressed (14%), 1 had recurrence (4%)
      and 4 patients died, however, only 2 (10%) of these due to bladder cancer. Of all
      patients receiving BCG immunotherapy, 8 (27%) had significant side effects. The
      incidence and treatment of patients with CIS of urinary bladder in our
      institution is comparable to other recent literature reports.

PMID- 23115944
TI  - Retinopathy of prematurity and serum level of insulin-like growth factor-1.
AB  - The aim of our study was to measure and compare serum insulin-like growth factor
      1 (IGF-1) levels at postmenstrual age of 33 weeks between preterm infants with
      and without retinopathy of prematurity (ROP). ROP occurs in two phases. Low serum
      levels of IGF-1 during ROP phase 1 have been found to correlate with the severity
      of ROP. ROP phase 2 begins around postmenstrual week 33. We conducted a
      prospective cohort study to measure serum IGF-1 levels in premature infants at
      postmenstrual age of 33 weeks. The study included all premature infants (N = 74),
      gestational age < or = 33 weeks, hospitalized at Department of Neonatology,
      Clinical Center of Montenegro, from April 2008 to July 2009. The incidence of ROP
      in the study cohort was 50.7%. Infants with ROP had a significantly lower birth
      weight and significantly shorter gestational age. The mean level of IGF-1 at
      postmenstrual age of 33 weeks was 23.7 mcg/L. Study results showed that there was
      no significant difference in serum IGF-1 level between newborns with and without
      ROP at postmenstrual age of 33 weeks (in newborns with ROP, it was the beginning
      of ROP phase 2). A large controlled study with repeated measurement of IGF-1
      level in the neonatal period is needed to confirm that restoration of IGF-I level
      occurs in ROP phase 2, i.e. that the low level of IGF-1 is only a feature of ROP
      phase 1.

PMID- 23115945
TI  - Brain tumor as a prototype of severe brain lesion in patients with "low T3
      syndrome".
AB  - The purpose of our study was to contribute to better understanding of
      cerebrospinal fluid (CSF) as a valuable biological material in the research of
      brain tumors within the "low T3 syndrome", and to discuss the role of thyroid
      hormones in the central nervous system in subjects with severe cerebral lesions.
      We studied the levels of total triiodothyronine (tT3), total thyroxine (tT4),
      free triiodothyronine (fT3), free thyroxine (fT4), reverse triiodothyronine (rT3)
      and thyrotropin (TSH) in serum, and fT3, fT4, rT3 and TSH levels in CSF of
      patients with brain tumor, and compared the results with control group. Study
      results indicated a statistically significantly higher level of rT3 in serum and
      CSF of brain tumor patients vs. control group (p < 0.05). The rT3/fT3 ratio was
      highest in CSF and serum of brain tumor patients, yielding a statistically
      significant difference (p < 0.05). These results could suggest higher
      permeability of the blood-brain barrier in brain tumor patients. We also assume
      that rT3, in the framework of"cerebral low T3 syndrome", is also generated
      through local intracerebral conversion. Disruption of this process in severe
      cerebral lesion can lead to increased rT3 concentrations, i.e. development of the
      "low T3 syndrome".

PMID- 23115946
TI  - Aphasia in patients with ischemic stroke.
AB  - Aphasia in ischemic stroke patients is associated with increased mortality,
      decreased rates of functional recovery, and reduced work capability. The aim was
      to study the prevalence and characteristics of aphasia in ischemic stroke
      patients. This prospective, cohort study included 177 patients (94 male and 83
      female) hospitalized for ischemic stroke at University Department of Neurology in
      Osijek in 2010. All patients were examined by a neurologist and speech therapist
      to specify the subtype of stroke and speech disturbance. The study showed 75
      (42.4%) study patients to have aphasia (48.2% of females and 37.2% of males). The
      most frequent clinical type was expressive-receptive aphasia. Aphasic patients
      were statistically significantly older (75 vs. 70 years) and showed female
      predominance (53% vs. 42%). Patients with aphasia also had a threefold share of
      large vessel stroke (51% vs. 17%) and approximately twofold share of
      cardioembolic stroke (41% vs. 22%). The share of left hemisphere stroke was
      nearly twofold in aphasic (61%) compared to non-aphasic (31%) patients. The study
      showed a high prevalence of aphasia in patients with ischemic stroke, which
      increased with age, was more pronounced in females and most frequently found in
      patients suffering from large vessel stroke and cardioembolic stroke.

PMID- 23115947
TI  - The protective effects of resveratrol on human coronary artery endothelial cell
      damage induced by hydrogen peroxide in vitro.
AB  - Oxidative stress is defined as imbalance between the production and destruction
      of reactive oxygen species. The aim of this study was to investigate whether
      resveratrol could protect human endothelial cells against hydrogen peroxide
      damage in vitro. In this in vitro study on human coronary endothelial cells, the
      effects of resveratrol on the glutathione content in human coronary endothelial
      cells in vitro were evaluated with high performance liquid chromatography. The
      effects of resveratrol on protein expression of the glutamate cysteine ligase,
      glutathione peroxidase and glutathione reductase enzymes were evaluated with the
      Western blot method. Resveratrol increased the reduced glutathione contents
      significantly (p < 0.05). Resveratrol increased protein expression of the
      glutamate cysteine ligase, glutathione peroxidase-1 and glutathione reductase
      enzymes (p < 0.05). All data supported each other and suggested that resveratrol
      had a protective effect against human coronary artery endothelial cell damage. It
      is thought that these results could pave the way to the new therapeutic
      approaches to protect against oxidative stress that develops in cardiovascular
      diseases.

PMID- 23115948
TI  - Intensity and distribution of immunohistochemical expression of galectin-3 in
      thyroid neoplasms.
AB  - The aim of the study was to assess the intensity and distribution of galectin-3
      expression in benign and malignant thyroid neoplasms by immunohistochemical
      method. Immunohistochemical expression of galectin-3 was analyzed in surgical
      thyroid specimens from 82 patients with histopathologic diagnosis of follicular
      adenoma (n = 32), Hurthle cell adenoma (n = 10) and papillary carcinoma (n = 40).
      Results of intracytoplasmatic and intranuclear expression of galectin-3 were
      scored using a semi-quantitative scale for intensity. Intracytoplasmatic
      expression ofgalectin-3 was positive in 18 (43%) benign neoplasms and in all 40
      malignant neoplasms. The accuracy, sensitivity and specificity of
      intracytoplasmatic expression of galectin-3 as a malignant marker in thyroid
      neoplasms were 78.1%, 100% and 57.1%, respectively. Intracytoplasmatic expression
      of galectin-3 was positive in 10 (31%) cases of follicular adenoma and 8 (80%)
      cases of Hurthle cell adenoma. The accuracy, sensitivity and specificity of
      intranuclear expression of galectin-3 as a malignant marker in thyroid neoplasms
      were 84.1%, 100% and 69%, respectively. There was no strong intensity of either
      intracytoplasmatic or intranuclear expression ofgalectin-3 in benign thyroid
      neoplasms, and no weak intensity of either intracytoplasmatic or intranuclear
      expression of galectin-3 in malignant neoplasms. There was no statistically
      significant difference between intracytoplasmatic and intranuclear expression of
      galectin-3 in benign thyroid neoplasms. The results of our study indicate that
      the immunohistochemical expression of galectin-3 is a highly sensitive marker of
      malignancy, with low specificity in differentiating malignant from benign thyroid
      neoplasms. The analysis of intensity and distribution ofgalectin-3 expression
      could improve the specificity of the method.

PMID- 23115949
TI  - Anxiety and depressive symptoms in acute ischemic stroke.
AB  - Inadequate attention is being paid to the anxiety and depressive symptoms in
      acute stroke, although these problems are known to influence the patients'
      neurological outcome. The aim of our study was to assess the prevalence of
      anxiety and depressive symptoms in the acute stage of ischemic stroke and to
      identify the factors associated with such problems. Anxiety and depressive
      symptoms were evaluated using the Hospital Anxiety and Depression Scale in 40
      patients with acute ischemic stroke admitted during a period of one month.
      Statistical analyses were performed by the SigmaStat (Version 2.0) software.
      Study results showed 55% of study patients to suffer from depressive symptoms and
      40% from both anxiety symptoms and depressive symptoms. There was a correlation
      of depressive symptoms (HADS-D score) with MMSE (p < 0.001), age (p = 0.003) and
      BI (p < 0.001), and of anxiety symptoms (HADS-A score) with MMSE (p < 0.001) and
      BI (p = 0.01). There was no significant association of HADS-A and HADS-D score
      with other patient characteristics. In conclusion, depressive symptoms were more
      frequent in the acute stage ofischemic stroke. Study patients had a high
      prevalence of both groups of symptoms. Therefore, attention should be paid to the
      anxiety and depressive symptoms in stroke units and try to relieve the patients'
      emotional stress and personal suffering, which could improve their neurological
      outcome.

PMID- 23115950
TI  - Clinical aspects of posterior uveitis in ocular sarcoidosis.
AB  - Two clinical forms of the "white spot" syndrome in patients with posterior
      uveitis in definitive and presumable ocular sarcoidosis were analyzed. Group 1
      was characterized by periphlebitis and discrete white spots around the vein of
      the retina, so-called "candle-wax", whereas group 2 showed yellow-orange solitary
      nodules located at the choroid, i.e. multifocal choroiditis. Visual acuity and
      the severity of clinical presentation were assessed in both groups. Visual
      acuity, Snellen equivalent was 0.52 +/- 0.36 in group 1 and 0.82 +/- 0.39 in
      group 2 with lesions at the level of choroid. One-way analysis of variance ANOVA
      showed a statistically significant between-group difference in visual acuity (p =
      0.03). The mean severity of clinical presentation was 11.80 +/- 2.04 points in
      group 1 and 5.80 +/- 4.18 points in group 2. T-test for independent samples
      yielded a statistically significant difference between the groups (p = 0.02). A
      statistically significant difference in visual acuity was the result of
      vasculitis in the group with the "candle-wax" phenomenon, which is associated
      with retinal vasculitis and causes cystoid macular edema and reduction of visual
      acuity. Complications such as cataract, glaucoma and neovascularization, which
      also decrease visual acuity, were more frequent in group 1.

PMID- 23115951
TI  - Platybasia and Klippel Feil-syndrome: case report.
AB  - A case is presented of a 35-year-old woman diagnosed with platybasia associated
      with Klippel-Feil syndrome type I. She was admitted to University Department of
      Neurology for clinical examination because of walking difficulties, dizziness,
      and intermittent vision disturbances. Neurological examination revealed a
      predominance of cerebellar symptomatology. Relevant diagnostic work-up included
      craniogram, cervical spine x-ray, computed tomography (CT) of the brain and
      craniocervical junction, magnetic resonance imaging of the brain,
      electroencephalography, ophthalmologic examination, urinary tract
      ultrasonography, laboratory tests, and psychological testing. CT of the
      craniocervical junction showed platybasia, congenital fusion of the second and
      third cervical vertebrae, and basilar invagination of dens axis. Platybasia is
      leveling of the angle between the floor of the anterior cranial fossa and
      posterior cranial fossa in the area of sella turcica, which is normally at 115
      140 degrees. Basilar impression or invagination is moving up of the basis of the
      occiput and occipital condyles into the cranium, which means that the borders of
      the foramen magnum, condyles and adjacent bone are invaginated into the posterior
      fossa. Klippel-Feil syndrome type II is massive fusion of two of seven cervical
      vertebrae associated with short neck and low hair line.

PMID- 23115952
TI  - Abdominal wall endometriosis: case report.
AB  - Abdominal wall endometriosis, also known as scar endometrioma, is a rare
      condition, in most cases occurring after previous cesarean section or pelvic
      surgery. The incidence of scar endometrioma is estimated to 0.03%-1.5% of all
      women with previous cesarean delivery. The predominant clinical picture is cyclic
      pain. Due to a wide range of mimicking conditions and a relative rarity, a
      significant delay is often observed from the onset of symptoms to proper
      treatment. We report on a case of a 36-year-old patient with scar endometrioma
      after two previous cesarean deliveries. The possible diagnostic pitfalls and
      treatment options are discussed.

PMID- 23115953
TI  - Genu recurvatum as a complication after total knee arthroplasty.
AB  - A 73-year-old female patient underwent total knee arthroplasty for arthrosis.
      After surgery, recurvatum instability over 55 degrees occurred. Two years later,
      primary endoprosthesis was removed and a revision endoprosthesis implanted.
      However, complete deformity occurred again. Two years later, the thickest
      revision polyethylene tibial implant was implanted on the same endoprosthesis. In
      spite of using knee orthosis, recurvatum deformity returned. Seven months later,
      new revision rotating hinge prosthesis was implanted. This procedure seems to
      have solved the problem. The knee deformity in this specific case was larger than
      the deformity in cases reported so far, and it was solved after three surgical
      procedures. Rotating hinge prosthesis seems to be the method of choice for
      immediate repair of recurvatum instability after total knee arthroplasty.

PMID- 23115954
TI  - False-positive methadone urine drug screen in a patient treated with quetiapine.
AB  - We present a case of T.M. admitted to University Department of Psychiatry, Split
      University Hospital Center, in Croatia, because of the acute psychotic reaction
      (F23.9). The patient's urine tested positive for methadone without a history of
      methadone ingestion. Urine drug screen was performed with the COBAS Integra
      Methadone II test kit (kinetic interaction of microparticles in solution /KIMS/
      methodology) by Roche. Drugs that have been shown to cross-react with methadone
      feature a tricyclic structure with a sulfur and nitrogen atom in the middle ring,
      which is common for both quetiapine and methadone. Therefore, it is plausible
      that this structural similarity between quetiapine and methadone could underlie
      the cross-reactivity on methadone drug screen. Besides quetiapine, a number of
      routinely prescribed medications have been associated with triggering false
      positive urine drug screen results. Verification of the test results with a
      different screening test or additional analytical tests should be performed to
      avoid adverse consequences for the patients.

PMID- 23115955
TI  - Prevalence, distribution and types of corneal astigmatism in cataract surgery
      patients in Sibenik County.
AB  - The aim of the study was to determine the prevalence, distribution and types of
      corneal astigmatism in cataract surgery patients in Sibenik County. In this
      retrospective study, keratometric data on 392 eyes of 202 patients admitted for
      senile cataract surgery to Sibenik General Hospital from April until June 2011
      were collected and statistically analyzed. The median age of our patients was 77
      (range 50 to 92) years; there were 91 (45%) men and 111 (55%) women. The measured
      keratometric values ranged from 36.00 to 47.00 diopter. The median of measured
      corneal astigmatism was 0.75 diopter cylinders (DCyl), ranging from 0 to 6.12
      DCyl. In 150 (38.3%) study eyes, corneal astigmatism was in the physiological
      range of 0.50 DCyl or less, in 118 (30.1%) eyes it was > 0.50-1.0 DCyl, and in
      124 (31.6%) eyes > 1.0 DCyl. Preoperative corneal astigmatism of 1 DCyl or more
      has a significant influence on postoperative refractive outcome. This imposes the
      need to consider a possible option for correction of preoperative astigmatism at
      the time of cataract surgery.

PMID- 23115956
TI  - Sub-Bowman keratomileusis compared with photorefractive keratectomy-
      contralateral eye study.
AB  - The aim of this study was to compare two different refractive surgery approaches
      in correction of myopia with or without astigmatism. In patients where one eye
      underwent sub-Bowman keratomileusis (SBK) and the other eye photorefractive
      keratectomy (PRK), the objective and subjective results were retrospectively
      compared during the six-month follow-up. Eighty four patients (168 eyes) were
      involved in this retrospective contralateral study. The mean preoperative
      spherical refraction was -3.88 diopters (D) and the mean cylinder was -0.82 D for
      all eyes. Each patient underwent SBK on one eye and PRK on the contralateral eye.
      The eyes in the PRK group underwent mechanical epithelial removal, which was
      followed by laser treatment. Mitomycin C 0.02% was used for 15 seconds if
      ablation was deeper than 50 microns. In the SBK group, the intended 100-microm
      corneal flap was created with IntraLase femtosecond laser. All eyes underwent
      customized wavefront guided laser ablation using a VISX Star S4 IR excimer laser.
      Preoperative and postoperative outcome measures included best spectacle-corrected
      visual acuity, uncorrected visual acuity, corneal topography, contrast visual
      acuity, and anterior optical coherence tomography imaging. Patients were asked to
      complete subjective satisfaction questionnaires at each visit. Through the first
      3 months of follow up, the SBK eyes demonstrated clinically and statistically
      better visual results than PRK eyes, between 3 and 6 months the results in the
      two groups began to equalize, and after 6 months of follow up there were no
      clinical and statistical differences between the SBK and PRK groups. SBK seems to
      be more practical for the patient with less pain, faster visual recovery, fewer
      medications, and overall superior experience.

PMID- 23115957
TI  - Astigmatism and diagnostic procedures.
AB  - Astigmatism represents an inability of the cornea and lens to provide a sharp
      image onto the retina. Correcting astigmatic errors, whether congenital, contact
      lens induced or surgically induced, is now an integral part of modern cataract
      and refractive procedures. Development of modern technology has enabled accurate
      diagnosis and perfect opportunities for correction; however, while cataract and
      keratorefractive surgery have come a long way in the last decade, the treatment
      and diagnosis of astigmatism continue to challenge ophthalmologists. There are
      several diagnostic procedures and tools available today, some standard and some
      contemporary that include keratometry, corneal topography, apparatus using
      wavefront or Scheimpflug analysis like Orbscan, Pentacam, Wavescan, etc. With the
      introduction of several new diagnostic tools, measurements of astigmatism have
      become less of an issue, but in some cases it is still difficult to obtain
      consistent results. What remains still unanswered is the question of the best
      diagnostic tool on the market. Further research is needed to evaluate both tools
      as well as their clinical application for optimal use.

PMID- 23115958
TI  - Limbal relaxing incision during cataract surgery.
AB  - Limbal relaxing incisions are one of the more commonly performed procedures with
      phacoemulsification to correct preexisting astigmatism during cataract surgery.
      The aim of the study was to evaluate the effect and stability of limbal relaxing
      incisions in reducing preexisting astigmatism at the time of phacoemulsification.
      The study included 10 eyes in 12 patients who underwent limbal relaxing incisions
      during cataract surgery, with preexisting astigmatism of 1-2 diopter (D).
      Assessments were made preoperatively, and 1 and 3 months postoperatively. Outcome
      measures included uncorrected distance visual acuity, best corrected distance
      visual acuity and keratometric astigmatism measures. The mean preoperative and
      postoperative refractive astigmatism was 1.50 D (+/- 0.75D) and 0.25 D (+/- 0.25
      D), respectively. There were no serious postoperative complications. Limbal
      relaxing incisions provide a viable option for correcting preexisting astigmatism
      at the time of cataract surgery with mild complications.

PMID- 23115959
TI  - Toric intraocular lens implantation for astigmatism correction in cataract
      surgery.
AB  - The aim of this study was to evaluate clinical outcomes after toric intraocular
      lens implantation for astigmatism correction in patients undergoing cataract
      surgery. This prospective observational study included eyes undergoing cataract
      surgery at Sestre milosrdnice University Hospital Center between February and
      September 2011. The study enrolled eyes that had visually significant cataract
      and preexisting regular corneal astigmatism of 1.50 D or greater.
      Phacoemulsification was performed and all eyes received an AT TORBI 709 M toric
      foldable intraocular lens. At 3 months, the uncorrected distance visual acuity
      was 0.8 or better in 9 of 10 eyes. At 3 months postoperatively, the median
      reduction in refractive cylinder was statistically significant (P < 0.05). The
      median intraocular lens axis rotation was 3.0 degrees interquartile range (2.0
      4.0 degrees). Our results showed AT TORBI 709 IOL to be an effective surgical
      option to correct preexisting corneal astigmatism and spectacle dependence after
      cataract surgery.

PMID- 23115960
TI  - Excimer laser correction of hyperopia, hyperopic and mixed astigmatism: past,
      present, and future.
AB  - The broad acceptance of "spot scanning" or "flying spot" excimer lasers in the
      last decade has enabled the domination of corneal ablative laser surgery over
      other refractive surgical procedures for the correction of hyperopia, hyperopic
      and mixed astigmatism. This review outlines the most important reasons why the
      ablative laser correction of hyperopia, hyperopic and mixed astigmatism for many
      years lagged behind that of myopia. Most of today's scanning laser systems, used
      in the LASIK and PRK procedures, can safely and effectively perform low, moderate
      and high hyperopic and hyperopic astigmatic corrections. The introduction of
      these laser platforms has also significantly improved the long term refractive
      stability of hyperopic treatments. In the future, further improvements in
      femtosecond and nanosecond technology, eye-tracker systems, and the development
      of new customized algorithms, such as the ray-tracing method, could additionally
      increase the upper limit for the safe and predictable corneal ablative laser
      correction ofhyperopia, hyperopic and mixed astigmatism.

PMID- 23115961
TI  - Correction of astigmatism with contact lenses.
AB  - Contact lens correction of astigmatism is reviewed. According to literature data,
      rigid gas permeable lenses are the lenses of choice in correction of irregular
      and high astigmatism. The crucial advantage of rigid gas permeable lenses is
      clear vision and stable correction of astigmatism. Soft toric lenses ensure quick
      adaptation and comfort. The most prominent disadvantage of soft toric contact
      lenses is variable visual acuity caused by lens rotation.

PMID- 23115962
TI  - Historical review.

PMID- 23115963
TI  - [Research advances in actinomycete ATP-binding cassette transporters--a review].
AB  - Actinomycetes can produce numerous secondary metabolites with novel structures
      and unique bioactivities, which are significant for pharmaceutical industry,
      agriculture and environmental protection. Whole-genome sequencing data
      demonstrate that actinomycetes contain plenty genes coding for transporters with
      ATP-binding cassette (ABC), which play important roles in nutrient uptake,
      secondary metabolite export, xenogenous toxin detoxification, and so on. In this
      review, the structures and mechanisms of the ABC transporters were described. We
      also comprehensively discussed research advances including ours on actinomycete
      ABC transporters, with emphasis on ABC exporters responsible for the secretion of
      secondary metabolites. Finally, research hotspots and application prospect of
      actinomycete ABC transporters were also addressed.

PMID- 23115964
TI  - [Present status and prospects for the detection of Bacillus anthracis--a review].
AB  - Anthrax, as a fulminating infectious disease, threatens human' s health
      seriously. Bacillus anthracis, the agent of anthrax, was classified into the
      second kinds of pathogenic microorganisms (one kind of the highly pathogenic
      microorganism) in the List of Human Pathogenic Microorganisms issued by the
      Chinese government. The spores formed by B. anthracis are potential material for
      biological warfare agent and biological terror. Therefore, it is very important
      and pressing to develop sensitive, efficient detection methods for the bacteria.
      For detection methods of B. anthracis, there are four types of targets : spores,
      vegetative cells, genes and anthrax toxin proteins. Among them, detection methods
      targeting spores and vegetative cells are developed. However, owing to
      disadvantages in specificity and clinical practicality, these methods are far
      from satisfaction. Detection methods targeting genes of B. anthracis are
      satisfactory in specificity and sensitivity, while it is short in clinical
      diagnosis. At the same time, the development of detection methods targeting
      anthrax toxin makes it possible to acquire information about main causative agent
      directly, which brings about great help in clinical diagnosis as well as
      epidemiology research. Herein, we summarized briefly detection methods of B.
      anthracis developed currently, investigated their application ranges and
      detection capacity, and discussed the development trend of related research,
      expecting favoring the profession developing detection methods of B. anthracis.

PMID- 23115965
TI  - [Isolation methods and diversity of culturable fecal actinobacteria associated
      with Panthera tigris tigris in Yunnan Safari Park].
AB  - OBJECTIVE: We studied the isolation methods and diversity of culturable fecal
      actinobacteria associated with Panthera tigris tigris by using culture-dependent
      approaches. METHODS: Fresh fecal samples of healthy Panthera tigris tigris were
      collected from Yunnan Safari Park. Pretreatment of the samples, isolation media
      and inhibitors were tested for actinobacteria isolation. 16S rRNA genes of
      actinobacteria were sequenced and subjected to phylogenetic analysis. RESULTS:
      The abundance of culturable actinobacteria was 1.10 x 10(8) cfu/g colony forming
      units (CFU) per gram of feces (wet weight). We obtained 110 purified cultural
      actinobacterium strains. The analysis based on 16S rRNA gene sequences showed
      that these strains were distributed in 10 different families and 12 genera of
      actinobacteria at least, and most of them were non-filamentous, such as
      Arthrobacter, Dietzia, Kocuria, Corynebacterium and Microbacterium. Streptomyces
      was the mainly classical filamentous actinobacteria, and up to 64% of total.
      CONCLUSION: Drying and heating up the fecal samples can greatly increase the rate
      of the actinobacteria. Many kinds of inhibitors and chemical defined media are
      suitable for isolation of fecal actinobacteria. The culturable actinobacteria are
      abundant in Panthera tigris tigris feces. Our study found an effective method to
      isolate animals' fecal actinobacteria and it's useful for studying and exploiting
      animals' fecal actinobacteria.

PMID- 23115966
TI  - [Plasmid pCQ4 and its phage phiCQ4 of endophytic Streptomyces sp. from Artemisia
      annua L].
AB  - OBJECTIVE: Large plasmid pCQ4 was detected in Streptomyces sp. W75 from Artemisia
      annua L. We clonined, sequenced, analyzed and characterized pCQ4. METHODS:
      Southern hybridization was used to determine restriction map of pCQ4. To clone
      the full-length of pCQ4, conjugation and recombinational cloning in a BAC vector
      were used. RESULTS: The complete nucleotide sequence of pCQ4 consisted of 84833
      bp, encoding 129 ORFs which 40 ORFs resembled these of bacterial phages. W75
      culture could infect W75 cured of pCQ4 and formed plaques on plate. Phage
      particle (phiCQ4) was observed by transmission electron microscopy. LinearphiCQ4
      DNA was detected on pulsed-field gel electrophoresis. Comparison to Streptomyces
      plasmid-phage pZL12, genes encoding major phage structural proteins resembled
      that of pCQ4. CONCLUSION: Streptomyces plasmid pCQ4 could be transformed into
      lytic phagephiCQ4, and the phage segment on pCQ4 might be a mobile unit.

PMID- 23115967
TI  - [Novel DNA-beta associated molecules produced by sequence recombination and
      deletion of cotton leaf curl Multan virus complex].
AB  - OBJECTIVE: Cotton leaf curl disease (CLCuD) is a major constraint to cotton
      production, causing great economic losses in Pakistan and India. In China, CLCuD
      has been discovered in the field of Nanning, GuangXi. To better understand this
      disease, we sequenced the virus-associated small DNA molecules. METHODS: We
      purified total DNA from cotton and okra plants exhibiting leaf curl symptoms; PCR
      amplified and sequenced CLCuMV satellite DNA (DNAbeta) -related small DNA
      molecules. RESULTS: We identified 2 novel recombinant DNA molecules with 1384
      nucleotides in cotton and 754 nucleotides in okra. The 1384 nt molecule contains
      partial DNA-A and DNAbeta of CLCuMV GX1. It includes the intergenic region,
      adjacent AV2 and AC1 coding sequences, and reverse complementary AC3 of DNA-A and
      A-rich region of DNAbeta. Common nucleotides were found around the junction
      points of DNA-A and DNAbeta sequences, suggesting they were the sites of
      recombination. Comparison with previous reported CLCuMV recombinants produced in
      lab showed that the intergenic region of DNA-A and A-rich region of DNAbeta were
      conserved on the recombination process. The 754 nt molecule was produced by
      deletion of CLCuMV DNAbeta in the C1 open reading frame and A-rich region.
      CONCLUSION: We identified a novel recombinant molecule originated from CLCuMV DNA
      A and DNAbeta and a small defective molecule of DNAbeta. This is the first report
      of sequence recombination and deletion of CLCuMV in China, which may be helpful
      to understand the CLCuMV evolution and host adaptation.

PMID- 23115968
TI  - [AMP-activated protein kinase-alpha is involved in the autophagy and apoptosis
      caused by troglitazone].
AB  - OBJECTIVE: To reveal the mechanism of AMPK signaling in the autophagy and
      apoptosis caused by troglitazone (TZ). METHODS: To investigate the effect of TZ
      on alteration of autophagy and apoptosis in HeLa cells, fluorescence microscopy,
      electron microscopy, western-blotting, siRNA interference, flow cytometry and MTS
      assay were used. RESULTS: TZ attenuated AMP-activated protein kinase-alpha
      (AMPKalpha) phosphorylation, and stimulates autophagic process in HeLa cells. TZ
      induced the accumulation of microtubule-associated protein 1 light chain 3-II
      (LC3-II), and degradation of sequestosome 1 (SQSTM1/p62), two markers of
      autophagy, occurring prior to the caspase activation. Compound C, an AMPK
      inhibitor, increased basal and inhibits TZ-stimulated LC3-II content and TZ
      depended PARP cleavage. Knockdown of the gene encoding autophagic proteins and
      AMPK conferred the cells resistance to apoptosis by TZ. CONCLUSION: Taken
      together, these data demonstrate that AMPK is involved in TZ promote autophagy,
      which precedes and contributes to caspase-dependent apoptosis.

PMID- 23115969
TI  - [Overexpression and characterization of a laccase gene from Pleurotus ostreatus
      in Trichoderma reesei].
AB  - OBJECTIVE: Expression, purification and characterization of a laccase gene from
      Pleurotus ostreatus in Trichoderma reesei. METHODS: The strong promoter and
      terminator of cellobiohydrolase I (cbh1) gene from T. reesei were amplified by
      PCR and inserted into pBluescriptIISK(+) to form vector pSKCST. The laccase gene
      from Pleurotus ostreatus was de novo synthesized according to T. reesei condon
      bias and cloned into the vector pLacdt resulting in the expression vector pSKLDT.
      The linearized pSKLDT was introduced into T. reesei strain Tu6 by protoplast
      mediated transformation. The screened laccase expression transformants were grown
      in shake flasks on minimal medium and the recombinant laccase was purified and
      characterized. RESULTS: Transformants were isolated in selective screening medium
      plate and identified by PCR. The enzyme activity of laccase in transformant LC-7
      was 237.134 U/mL which was 28.6 -fold higher than that in P. ostreatus. The
      specific activity of the purified enzyme was 9852 IU/mg. Enzymatic assay revealed
      that the optimum temperature for its activity was 50 degrees C and pH was 3.0.
      The optimum substrate was ABTS and the K(m) and V(max) for ABTS were 7.58 x 10(
      2) mmol/L and 9.752 x 10(-3) mmol/L/min. Metal ions like Cu2+, Zn2+, Fe3+, Mn2+,
      Ba2+, Mg2+ and Fe2+ had different inhibitory effect on purified laccase.
      CONCLUSIONS: Under the regulation of cbh1 promoter and cbh1 signal peptide,
      heterologous laccase was successfully overexpressed in T. reesei.

PMID- 23115970
TI  - [Cell surface display of Thermomyces lanuginosus lipase in Pichia pastoris and
      its characterization].
AB  - OBJECTIVE: To construct a novel cell-surface display system of Thermomyces
      lanuginosus lipase (TLL) based on an efficient anchor protein Sedlp in Pichia
      pastoris, to screen recombinant strains with high enzyme activity and displaying
      rate, and further to characterize the enzyme. METHODS: The lipase gene from T.
      lanuginosus was sub-cloned and fused with the anchor protein gene sed1 from
      Saccharomyces cerevisiae to construct a display vector pPICZalphaA-TLS. The
      vector pPICZalphaA-TLS was linearized by Sac I and then transformed into P.
      pastoris GS115 by electroporation. After screening by tributyrin medium, a clone
      exhibiting the maximum lipase activity in shaking flask was chosen to treat with
      rabbit anti-FLAG-tag and R-PE-conjugated goat anti-rabbit IgG, and then its
      positive location on the cell wall was detected by fluorescence microscope and
      flow cytometer. The recombinant strain displaying TLL was further characterized
      as a whole-cell catalyst. RESULTS: A novel cell-surface display system of T.
      lanuginosus lipase was successfully established, and a clone with lipase activity
      of 257.8 U/g dry cells in shaking flask was obtained. The displayed TLL on the
      cell surface was confirmed by immunofluorescence, and the treated cells under the
      fluorescence microscope emitted brightly red fluorescence, and the displaying
      rate was 98.36% detected by Flow Cytometer. The displayed TLL exhibited excellent
      thermostability and high tolerance to some organic solvents, and its maximal
      activity was observed at 30 degrees C and pH 8.0. The lipase activity was a
      little enhanced by K+, Ca2+ and Mg2+ and strongly inhibited by Cu2+, Mn2+ and
      Ni2+. However, ethylenediaminetetraacetic acid (EDTA), Sodium lauryl sulfate
      (SDS) and Tween 20 showed little effect on the displayed TLL. CONCLUSION: The
      lipase TLL was successfully displayed on the cell surface of P. pastoris by the
      anchor protein Sed1p for the first time to obtain a whole-cell catalyst, which
      had high hydrolytic activity and excellent enzymatic characterization. Thus, we
      here established a solid foundation for industrial applications of the displayed
      lipase TLL.

PMID- 23115971
TI  - [Microbial conversion of daidzein affects fecal equol concentration and bacterial
      composition of rats with or without ovariectomy].
AB  - Equol is the end metabolite of daidzein by certain intestinal bacteria, which has
      stronger bioactivity comparing with daidzein. OBJECTIVE: To evaluate the role of
      orally administrated equol-producing bacterium on increasing equol production and
      shifting intestinal microbiota of embracer animal. METHODS: In total 60 rats with
      or without ovariectomy at average bodyweight 211 +/- 9g were divided into 5
      groups. The differences on equol concentration and bacterial composition were
      compared in rats orally treated with distilled water, estradiol, daidzein, equol
      and daidzein + ZX7. RESULTS: The fecal equol concentration in daidzein groups was
      significantly higher than that in control and estradiol groups. The fecal equol
      concentration in daidzein + ZX7 groups was comparable to that in equol groups.
      Principal Components Analysis (PCA) of fecal DGGE profiles showed clear
      difference of fecal microbiota between ovariectomy done or undone rats. Fecal
      population of Bacteriodetes showed strong correlation with fecal equol
      concentration. CONCLUSION: Normal intestinal microbiota in rats might have the
      capacity to convert daidzein into equol. Dietary source of equol-producing
      bacterium ZX7 might have the possibility to increase the equol production of
      embracer animal. Endogenous estrogen concentration might shift the intestinal
      microbiota on rats. Bacteriodetes might have an important role on equol
      production.

PMID- 23115972
TI  - [Characteristics of the eukaryotic community structure in acid mine drainage lake
      in Anhui Province, China].
AB  - OBJECTIVE: We characterized eukaryotic community structure and the relationship
      between the community structure and environmental factors in acidic mine drainage
      (AMD) lake of a sulfide mine in Anhui Province, China. METHODS: The 18S rRNA gene
      clone libraries were constructed by using molecular biology techniques to analyze
      the eukaryotic phylogenetic relationships, and the canonical correspondence
      analysis (CCA) was used to analyze the relationship between the community
      structure and environmental factors. RESULTS: The phylogenetic analysis shows
      that Ascomycota is widespread in the four samples and dominated in the AMD-1 and
      AMD-3 clone libraries, whereas Chlorophyta and Basidiomycota are the predominant
      in AMD-2 and AMD-4 samples, respectively. Moreover, many sequences in libraries
      were closely related to those of acid-resisting and metal-resisting eukaryotic
      microbes, such as Sarcinomyces petricola, Penicillium janthinellum, Coniochaeta
      velutina, Trichoderma viride, Chlorella protothecoides var. acidicola, Ochromonas
      sp., and there are high content of known human pathogens, such as Lecythophora
      hoffmannii, Cryptococcus neoformans. CCA analysis revealed that the critical
      factors influencing the eukaryotic community structure include TN, SO4(2-), Fe2+
      and Eh. CONCLUSION: Difference of eukaryotic community structure in time and
      spare may be related with physico-chemical properties of acidic mine drainage.
      High content of human pathogens was detected in the acidic ecosystem. The
      ecological study of eukaryotes under the acidic conditions can help to find
      efficient methods to process acid mine drainage.

PMID- 23115973
TI  - [An IDP16 protein from Xenorhabdus bovienii depresses the immune response in
      Galleria mellonella].
AB  - OBJECTIVE: A protein with insect immunodepressive activity was purified from
      Xenorhabdus bovienii, a bacterial symbiosis of entomopathogenic nematode. To
      determine the function of this protein in the pathogenesis of bacterium-nematode
      symbiosis, we detected the effect of this protein on immune response in Galleria
      mellonella. METHODS: Proteins from extracellular extact of X. bovienii were
      purified using ammonium sulfate precipitation, HiTrap Q HP chromatography, HiTrap
      Butyl FF chromatography, and HiTrap SP HP chromatography. Intra-hemocoel
      injection assay followed by observation of hemolymph melanization was used for
      activity determination. Fluorescent microspheres and sepharose beads were used to
      assess the effect of purified protein on phagocytosis and encapsulation of
      hemocytes, respectively. The purified protein was identified by 2-D and MS
      anlysis. The full-length encoding gene was cloned by PCR, and expressed with pET
      30a in Escherichia coli. The recombinant protein was purified by Ni-NTA affinity
      chromatography. RESULTS: An immunodepressive protein was purified and designed as
      IDP16, which can inhibit the phenoloxidase activity, and weaken the phagocytosis
      and encapsulation of Galleria mellonella hemocytes. The encoding gene was then
      cloned and expressed in E. coli. The recombinant protein was also determined to
      be immunodepressive. CONCLUSION: The IDP16 protein from Xenorhabdus bovienii can
      depress the immune response in insect, which may play an important role in
      bacteria-host interaction.

PMID- 23115974
TI  - [Three successive extractions reduce quantification bias of microbial communities
      associated with incomplete DNA recovery in soil].
AB  - OBJECTIVE: To assess the quantification bias associated with incomplete
      extractions of soil microbial DNA and the feasibility of air-dried soil for
      microbial ecology study. METHODS: The flooded rice soil and upland wheat soil
      were used, and multiple extractions of soil microbial DNA was performed by lysing
      a single sample for 5 successive times. The copy number of 16S rRNA and amoA
      genes of Archaea and Bacteria was quantified in each DNA extraction by real-time.
      PCR. RESULTS: Cumulative DNA yields in 3 successive extractions accounted for
      more than 76% of microbial DNA in soils, and more than 77.5% of gene copies could
      be recovered. Air-drying decreased the abundance of bacterial 16S rRNA gene and
      archaeal 16S rRNA gene by 90.3% and 12.5%, and the abundance of bacterial and
      archaeal amoA genes showed a decline by 81.2% and 84.3%, respectively. The
      decline showed similar trend in two soils, suggesting air-dried soil could be of
      choice for biogeographic survey of microbial communities. CONCLUSION: Three
      successive extractions of microbial DNA in soil could be of choice for microbial
      ecology study in order to reduce quantification bias associated with incomplete
      DNA recovery. Air-dried soil could be employed under certain circumstances, and
      further investigation is warranted for the underlying mechanism by which
      microbial communities manage to survive the desiccation of soil.

PMID- 23115975
TI  - [Diversity of bacteria isolated from cysts Heterodera glycines in Heilongjiang].
AB  - OBJECTIVE: To understand the bacterial diversity isolated from the cysts of
      Heterodera glycines in the soybean field in Heilongjiang Province. METHODS:
      Bacteria were isolated from cysts on nutrient agar plates using dilution plate
      method and further identified by phylogenetic analysis based on 16S rDNA gene
      sequences. RESULTS: Totally 90 bacteria strains with different colony morphology
      were selected on nutrient agar plate and their phylogenetic features were
      analyzed based on the partial 16S rDNA sequences. In total 7 genera and 22
      species were identified, including 46 strains in Gammaproteobacteria (51.1%), 32
      in Firmicutes (35.6%), 10 in Betaproteobacteria (11.1%), and 2 in
      Alphaproteobacteria (2.2%). The dominant bacteria species were Pseudomonas and
      Bacillus. CONCLUSION: There was abundant species diversity of bacteria isolated
      from cysts Heterodera glycines in Heilongjiang, and these bacteria may play a
      physical and ecological roles in nematodes.

PMID- 23115976
TI  - [Thermotolerance of Bacillus licheniformis CGMCC 3963 from high-temperature
      Daqu].
AB  - OBJECTIVE: The use of high-temperature Daqu is an important characteristic in
      Chinese Maotai-flavor liquor making. Thermostable bacteria are predominant in
      high-temperature Daqu. They play important roles in Maotai-flavor liquor making.
      Learning the mechanism of thermotolerant performance of bacteria would provide
      insight into characteristics of this liquor making. METHODS: We determined the
      thermotolerance of Bacillus licheniformis CGMCC 3963, and analyzed cell
      morphology, genomics and transcriptomics. RESULTS: B. licheniformis CGMCC 3963
      could survive at 55 degrees C and produce many capsules. Genes of class I heat
      shock proteins and polyglutamate biosynthesis were both up-regulated. CONCLUSION:
      Much heat-shock proteins and capsule polyglutamate maintained the survival of
      cell with heat stress.

PMID- 23115977
TI  - [Replication and conjugation of Streptomyces small plasmid pDYM4. 3k].
AB  - OBJECTIVE: Streptomyces sp. X335, harboring a 4. 3-kb plasmid pDYM4.3k, was
      isolated from Tibet sample. Cloning, sequencing, analyzing and functional
      investigations of pDYM4. 3k. METHODS: Prime walking to obtain plasmid sequence,
      BLAST to predict gene function, Southern hybridization to determine replication
      intermediates, and mating to test conjugal function of plasmid. RESULTS: The
      complete nucleotide sequence of pDYM4. 3k consisted of 4346 bp, encoding 3 genes
      of which one resembled Streptomyces major conjugative gene tra and other two were
      with unknown functions. Experiments demonstrated that a new gene of pDYM4. 3k and
      its upstream c. 300 bp were required for plasmid replication. Single-stranded
      pDYM4. 3k as a replication intermediate was detected, indicating it rolling-cirle
      replication mode. pDYM4.3k could conjugal transfer among Streptomyces lividans.
      CONCLUSION: Streptomyces small plasmid pDYM4. 3k was able to autonomous
      replication and conjugal transferring.

PMID- 23115978
TI  - [Using reporter gene to compare infection efficiency of HIV-1 pseudovirus to
      suspended and adherent cells].
AB  - OBJECTIVE: In order to compare the infection of HIV-1 pseudovirus to suspended
      and adherent cells, Tzmbl cells containing beta-gal (beta-galactosidase) reporter
      gene were used here to do the analysis. pseudoviruses were generated by co
      transfection of 293T cells with the plasmid pNL43R-E- and HIV envelope expressing
      plasmid. Supernatant of co-transfected 293T cells was collected and used to
      infect Tzmbl cells with or without trypsin treatment. Forty-eight hours after
      infection, beta-gal positive Tzmbl cells and virus infection were determined
      using X-gal staining and beta-glo (beta-galactosidase) assay. RESULTS: The
      efficiency of HIV pseudoviruses infection of suspended Tzmbl cell was higher than
      that of adherent cells and the increase of infection correlated with the
      pseudoviral subtype. CONCLUSION: This study may provide a useful method for HIV
      biological study and neutralization assays using a single-round replicative
      pseudovirus in the future.

PMID- 23115979
TI  - [Advance in fracture fixation of the lower extremity].

PMID- 23115980
TI  - [Treatment of long unstable femoral intertrochanteric fractures with locking
      plate and cable rope].
AB  - OBJECTIVE: To investigate clinical effect of long unstable femoral
      intertrochanteric fractures with locking plate and cable rope. METHODS: From June
      2004 to June 2010, twenty-six elderly patients with long unstable femoral
      intertrochanteric fractures were treated locking plate and cable rope
      fixation,included 16 males and 10 females with an average age of (58.23 +/- 4.45)
      years ranging from 50 to 65 years. There were 22 cases for traffic accident, 10
      of them for traffic accident with other injury; 4 cases for falling injury.
      According to Evans classification, 21 cases were in type I,among them 8 in type
      Ia, 10 in type Ib,2 in type Ic, 1 in type Id; the other 5 cases were type Hrd.
      Hip function scores were recorded to evaluate the treatment outcomes by Harris
      hip function score system. RESULTS: Twenty-six cases were followed-up for 9 to 18
      months (means 15 months). The operations were successful. All the patients
      received functional training for walking without weight loading from 7 to 14 days
      after operation, and walking gradually in weight loading from 6 weeks after
      operation,gradually fully weight loading from 12 weeks. The Harris hip function
      score were 77.31 +/- 13.97, involving pain 39.79 +/- 6.54, function 31.08 +/-
      9.45, deformity and activity 3.85 +/- 0.46. The clinical results were excellent
      in 10 cases, good in 13, fair in 3. CONCLUSION: Locking plate and cable rope is
      suiteable for the treatment of senile long femoral intertrochanteric fractures of
      every Evans type, especially benefit for osteoporosis patients.

PMID- 23115981
TI  - [Failure of internal fixation on displaced femoral neck fractures in adults under
      fifty-five years old].
AB  - OBJECTIVE: To investigate the failure of internal fixation on displaced femoral
      neck fractures in adults under fifty-five years old retrospectively inorder to
      pay more attention to the treatment of these fractures. METHODS: From Junary 2007
      to June 2010,18 failed cases of internal fixation on displaced femoral neck
      fractures in adults under fifty-five years old were treated,there were 13 males
      and 5 females with an average age of (48.0 +/- 6.0) years old ranging from 27 to
      55. Among them, 17 patients were treated with cannulated screws and 1 patient was
      treated with intramedullary nail; 16 patients were diagnosed as osteonecrosis and
      2 patients as osteonecrosis associated with nonunion. RESULTS: The average time
      from internal fixation to failure was 23 months (ranged, 8 to 32 months). The
      quality of fracture reduction in Garden index was poor. The Harris Hip Score was
      (56.0 +/- 12.5) (ranged,33 to 80). Eight cases of osteonecrosis and 2 cases of
      nonunion combinated osteonecrosis were received total hip arthroplasty. Hip
      resurfacing arthroplasty were performed for other 5 osteonecrosis. Because of no
      evident clinical symptoms,the other 3 cases received conservative treatment. The
      patients with total hip arthroplasty and hip resurfacing arthroplasty were
      followed-up for 34 months ranging from 12 to 53 months. After operation,the
      Harris score was (94.0 +/- 3.0) ranged 89 to 96. CONCLUSION: Osteonecrosis is a
      common complication after internal fixation on displaced femoral neck fracture in
      adults under fifty-five years old. More attention should be paid to the treatment
      of displaced femoral neck fracture in those patients.

PMID- 23115982
TI  - [Comparison of the effect between early anatomical open reduction, internal
      fixation and closed reduction, internal fixation for treatment of children
      displaced femoral neck fracture].
AB  - OBJECTIVE: To compared the effect between early anatomical open reduction,
      internal fixation (ORIF) and closed reduction, internal fixation (CRIF) for
      treatment of children displaced femoral neck fracture. METHODS: From March 2006
      to May 2010,34 children with displaced femoral neck fractures were reviewed
      retrospectively. These patients were divided into two groups. Among them, 19
      cases were treated by open reduction and internal fixation (ORIF) as group A,
      included 11 males and 8 females with an average age of (8.1 +/- 1.3), the other
      15 cases were treated by closed reduction and internal fixation (CRIF) as group
      B, included 9 males and 6 females with an average age of (7.9 +/- 1.5).
      Complications were observed and the short term effectiveness was evaluated by
      Ratliff standard. RESULTS: All children were followed-up from 1 to 3 years (means
      1.2 years). All fractures were healed. There was statistical different in the
      curative effects between the two groups (Z=2.389, P= 0.017). The incidence of
      complications in two groups had statistical different (P=0.046). CONCLUSION: The
      early ORIF could get better reduction with fewer complications than CRIF in
      fractures of the displaced femoral neck in children in Delbet type-II and type
      III, therefore, ORIF should be considered.

PMID- 23115983
TI  - [Comparison of three methods for the treatment of aged femoral intertrochanteric
      fracture].
AB  - OBJECTIVE: To investigate the reasonable methods of treatment for aged
      intertrochanteric fractures through the comparison and analysis about the
      clinical data and follow-up results of three kinds of treatment method of elderly
      intertrochanteric fractures. METHODS: From June 2004 to June 2010,131 patients
      with intertrochanteric fractures were treated and reviewed retrospectively. Among
      them, 72 patients were treated with dynamic hip screw (DHS) included 20 males and
      52 females with an average age of (72.5 +/- 5.5) years, 43 patients were treated
      with proximal femoral nail antirotation (PFNA) included 12 males and 31 females
      with an average age of (72.8 +/- 4.9) years and 16 patients were treated with
      hemiarthroplasty included 4 males and 12 females with an average age of (76.0 +/-
      5.0) years. The three groups of patients were statistically analyzed and compared
      on surgical trauma including operation time, blood loss, incision length, X-ray
      exposure, and on postoperative recovery including non-weight-bearing walking
      time, the hospitalization time, the healing time, the recovery of joint function
      and complications. RESULTS: All patients were followed-up from 6 months to 3
      years (means 18.2 months). In surgical trauma: the results of length of
      incision,operation time and blood loss was DHS>hemiarthroplasty>PFNA. PFNA group
      had the most X-ray exposure, hemiarthroplasty group had the least. In
      postoperative recovery: the results of in non-weight-bearing walking time,
      hospitalization time and healing time was DHS>PFNA>hemiarthroplasty. Harris
      scores at 12 weeks after operation in hemiarthroplasty was higher than that of
      DHS and PFNA, but there was no statistical difference between DHS and PFNA. The
      incidence of postoperative complications in DHS group was more than that of PFNA
      group, but there were not significant differences among three groups. CONCLUSION:
      PFNA is prepered in the treatment of senile intertrochanteric fractures. DHS
      fixation is more suitable for primary hospital and AI-type fracture and the
      fracture near the entry point of PFNA. The hemiarthroplasty is one of the best
      ways to treat unstable comminuted and/or severe osteoporosis of elderly
      intertrochanteric fracture. However,it isn't generally considered.

PMID- 23115984
TI  - [Minimally invasive percutaneous plate osteosynthesis for the treatment of
      intertrochanteric femoral fractures of Evans IlI and IV in elderly patients].
AB  - OBJECTIVE: To study therapeutic effects of minimally invasive percutaneous plate
      osteosynthesis for the treatment of intertrochanteric femoral fractures of Evans
      III, IV in elderly patients. METHODS: From December 2007 to April 2010, 23
      patients with intertrochanteric femoral fractures were reviewed. Among the
      patients, 11 patients were male and 12 patients were female,ranging in age from
      62 to 90 years, with a mean of 72.8 years. According to Evans classification, 13
      patients were type III and 10 patients were type IV. All the patients were
      treated with proximal femoral locking plate (minimally invasive percutaneous
      plate osteosynthesis, MIPPO) surgery. RESULTS: The operative time ranged from 45
      to 60 min, with an average of 50 min. The blood loss ranged from 60 to 100 ml,
      averaged 80 ml. All the patients were followed up,and the duration ranged from 9
      to 18 months, with an average of 11 months. The healing time based X-ray ranged
      from 3 to 6 months, with an average of 4 months. According to hip scoring
      criteria evaluation: 18 patients got an excellent results, 5 good. CONCLUSION:
      For the treatment of intertrochanteric femoral fractures of Evans III, IV in
      elderly patients, MIPPO has advantages such as small trauma, reliable fixation,
      which has good clinical application.

PMID- 23115985
TI  - [Treatment of complex tibial plateau fractures with bilateral locking plate and
      bone graft].
AB  - OBJECTIVE: To explore the effective methods for the treatment of complex tibial
      plateau fractures. METHODS: From May 2008 to April 2011, 28 patients with complex
      tibial plateau fractures were treated indirect reduction techniques, bilateral
      locking plate fixation combined with autologous bone grafts. There were 21 males
      and 7 females, with an average age of 43 years ranging from 21 to 65. There were
      11 cases in Schatzker type V, 17 in VI. The effect was evaluated by Rasmussen
      standard on clinical and radiological. RESULTS: All patients were followed-up for
      7 to 36 months (averaged of 21.5 months). Healing time of fracture was from 3 to
      8 months (averaged 5.5 months). The results of Rasmussen scores in clinical was
      4.50 +/- 1.32 in pain, 4.32 +/- 1.63 in walking ability, 4.07 +/- 1.34 in knee
      activity, 4.78 +/- 1.27 in stability of the knee, 4.85 +/- 1.12 in stretch knee;
      the results in radiation was 5.07 +/- 0.92 in articular surface collapse, 5.00 +/
      0.98 in platform widened, 5.14 +/- 0.85 in knee external varus. The effect
      result was excellent in 8 cases, good in 15, fair in 3 and poor in 2. CONCLUSION:
      The key for the treatment of complex tibial plateau fractures was to fully assess
      the damage as much as possible to protect the soft tissue, select the appropriate
      timing of surgery and surgical incision, application of indirect reduction
      techniques, limited incision and effective internal fixation to restore joint
      surface smooth and good limb alignment, early exercise, in order to achieve
      maximum recovery of joint function.

PMID- 23115986
TI  - [Open reduction and internal fixation via a posterior approach for posterior
      fractures of tibial plateau].
AB  - OBJECTIVE: To discuss the fracture patterns,operative procedures and clinical
      results of open reduction and internal fixation via a posterior approach to treat
      posterior fractures of tibial plateau. METHODS: From June 2008 to February 2011,
      8 patients with posterior tibial plateau fractures treated with posterior
      approach, were reviewed retrospectively. There were 5 males and 3 females,with an
      average of 41.1 years ranging from 23 to 55. Of the 8 cases, 5 cases were caused
      by traffic accidents, 3 caused by fall. Two cases of posterior coronal fractures
      combined with avulsion of posterior cruciate ligament and 1 case of
      posterolateral fractures associated with collapse fractures was treated via a S
      shaped approach, 2 cases of posteromedial fracture via a posteromedial reversed L
      shaped approach, another 3 cases of complex fractures involving anterior and
      posterior of tibial plateau, and metaphsis via a posteromedial reversed L-shaped
      approach combined with anterolateral approach. Fractures with articular surface
      collapse were applied with bone grafting. RESULTS: All the 8 cases were followed
      up for 8 to 39 months (means 20 months). All cases had attained bone union, the
      time of bone healing was 14.5 weeks in average ranging from 11 to 21 weeks. No
      infection, no blood vessel or nerve injuries and loosening or breakage of screw
      were found. There were no significant differences about the tibial plateau angle
      (TPA) and the posterior slope angle (PA) on radiographies between immediately
      after operation and 6 months after operation. According to the Rasmussen
      functional scoring,the results were excellent in 4, good in 3, fair in 1.
      Radiologic results were graded with the Rasmussen score to evaluate the reduction
      of the fracture, the scores at last followed-up was 14 to 18 scores (means
      17.25), the results were excellent in 6, good in 2. CONCLUSION: Posterior S
      shaped or L-shaped approach can facilitate the reduction and fixation with good
      exposure for posterior fractures of tibial plateau.

PMID- 23115987
TI  - [Close reduction by Chinese traditional manipulation and MIPPO for the treatment
      of tibial fractures in middle and distal segment].
AB  - OBJECTIVE: To explore the technique and clinical results of close manipulative
      reduction and minimally invasive percutaneous plate osteosynthesis (MIPPO) for
      the treatment of tibial fractures in the middle and distal segment. METHODS: From
      Jan. 2005 to Dec. 2009, 40 patients with tibial fractures in middle and distal
      segment were treated with close manipulative reduction and MIPPO fixation,
      including 28 males and 12 females with an average age of 54 years old (ranging
      from 21 to 76). According to AO fractures classification for the tibial fractures
      in the middle and distal segment, there were 26 cases of type A, 8 of type B, 6
      of type C. RESULTS: All patients were followed up for 12 to 24 months (averaged
      18 months). All the fractures gained bone healing, and the time required for the
      bony union ranged from 3 to 18 months (averaged 4 months). The patients were
      evaluated with respect to functional recovery according to Mazur Grating System
      for the ankle. The aggregate score was 96.67 +/- 3.91, involving pain 48.59 +/-
      2.28, hills up 2.95 +/- 0.22, hills down 2.85 +/- 0.37, stairs down 2.92 +/-
      0.35, run score 4.95 +/- 0.32, plantar flexion score 4.62 +/- 0.54, dorsiflexion
      score 4.13 +/- 0.61. The clinical results were excellent in 36 cases, good in 3
      and fair in 1. CONCLUSION: Close manipulative reduction and MIPPO fixation is a
      good method for the treatment of the tibial fractures in the middle and distal
      segment.

PMID- 23115988
TI  - [Clinical application of blocking screws and rooting technique in the treatment
      of distal tibial fracture with interlocking intramedullary nail].
AB  - OBJECTIVE: To introduce the clinical method of blocking screws and rooting
      technique in the treatment of distal tibial fracture with interlocking
      intramedullary nails. METHODS: From June 2006 to March 2011, 26 patients with
      distal tibial fracture were treated with interlocking intramedullary nails using
      blocking screws and rooting technique, included 18 males and 8 females with an
      average age of 46.2 years old ranging from 24 to 64 years. According to AO
      classification: 10 cases of type A1, 4 cases of type A2, 8 cases of type B1, 4
      cases of type B2. The average distance of the fractures end to the ankle joint
      was 85 mm ranging from 55 to 125 mm, the mean time between injured and operation
      was 4.5 days. The patients were evaluated with pain, range of motion, walking.
      RESULTS: All cases were followed-up for 6 to 22 months (averaged 15 months).
      According to Iowa ankle joint grading system,the score was improved from
      preoperative (66.8 +/- 8.2) to postoperative (94.6 +/- 4.8). All fractures had
      united, and got satisfactory reduction and stable fixation with no complications
      had happen such as breakage of screw. CONCLUSION: Fixation with interlocking
      intramedullary nail using blocking screws and rooting technique in treating
      distal tibial fracture, is a safe and effective technique for the improvement of
      stability.

PMID- 23115989
TI  - [Clinical randomized controlled trial on ultrashort wave and magnetic therapy for
      the treatment of early stage distal radius fractures].
AB  - OBJECTIVE: To explore the effect of application of ultrashort wave and magnetic
      therapy instrument on the swelling regression in distal radius fractures treated
      by splint external fixation in initial stage. METHODS: From March 2007 to May
      2010,90 patients with distal radial fracture were treated by manual reduction and
      splint external fixation. After manual reduction and small splints external
      fixation, these patients were randomly divided into electrical physical therapy
      group, western medicine group and the control group by the order of calling
      number, with 30 cases each group. In control group, there were 9 males and 21
      females with an average age of (61.29 +/- 1.97) years, the patients raised and
      exercise the limb and fingers only. The other two groups also carried out this
      treatment. In electrical physical therapy group, there were 9 males and 21
      females with an average age of (62.37 +/- 2.48) years, the patients were treated
      with ultrashort wave and magnetic therapy instrument for early intervention, once
      a day, 5 days for a course of treatment and three cycle were operated. In western
      medicine group,there were 8 males and 22 females with an average age of (60.12 +/
      2.87) years, the patients were injected with beta-aescin (20 mg, intravenous
      injection,once a day) for 5 days, followed by Danshen injection (20 ml,
      intravenous injection, once a day) for 10 days. The limb swelling of patients
      were assessed every day for 20 days after manual reduction and small splints
      external fixation. RESULTS: The time of swelling regression in electrical
      physical therapy group, western medicine group and the control group were
      respectively (9.62 +/- 3.32), (10.05 +/- 3.05) and (14.57 +/- 2.93) days. Both of
      that in electrical physical therapy group and western medicine group were shorter
      than that in the control group (P<0.05), then there were not statistical
      difference between electrical physical therapy group and western medicine group
      (P>0.05). The effective rate of swelling regression in electrical physical
      therapy group, western medicine group and the control group were 86.67%, 80.00%,
      46.66% respectively. There was no significant differences between electrical
      physical therapy group and western medicine group in the curative effect, but
      both of them had advantage over the control group. CONCLUSION: Application of
      ultrashort wave and magnetic therapy instrument for treatment of distal radial
      fractures in initial stage can promote the regression of limb swelling evidently,
      which is similar to the intravenous infusion of beta-aescin injection and Danshen
      injection in curative effect.

PMID- 23115990
TI  - [Case-control study on clavicular hook plate combined with acromiocoracoid
      ligament transfer in the treatment of acromioclavicular joint dislocation of type
      Tossy III in young patients].
AB  - OBJECTIVE: To study the clinical effects of acromiocoracoid ligament transfer to
      repair coracoclavicular ligament and acromioclavicular ligament in the treatment
      of acromioclavicular joint dislocation of type Tossy III in young patients.
      METHODS: From January 2005 to January 2007, 52 patients with acromioclavicular
      joint dislocation of type Tossy III were divided into therapeutic group I (32
      cases) and therapeutic group II (22 cases). There were 17 males and 13 females
      with an average age of 31.0 years (ranged, 19 to 40 years) in group I; as well as
      12 males and 10 females with an average age of 33.6 years (ranged, 20 to 42
      years) in group II. All the patients were fresh injury and the acromioclavicular
      joint dislocations were type Tossy III according to X-ray findings. The duration
      from damage to the operation time ranged from 2 to 17 days (averaged, 7.6 days).
      All the patients had normal shoulder function before injury and were treated with
      clavicular hook plate implantation. The patients in group II were treated with
      normal desmorrhaphy method, and the patients in group I were treated with
      acromiocoracoid ligament transfer to repair coracoclavicular ligament and
      acromioclavicular ligament. Steel plate was taken out at about 4 to 6 months
      after clavicular hook plate implantation. The results were evaluated according to
      Karlsson's standards. RESULTS: All the incisions healed without infection. The
      therapeutic effects of 52 patients were evaluated at the 6th month after internal
      fixation was taken out. Twenty-four patients in group I got an excellent results
      and 6 good; 17 patients in group II got an excellent results and 5 good. There
      was no significant difference between the two groups. Twenty-six patients in
      group I and 19 patients in group II had long-term follow-up, and the duration
      ranged from 3 to 5 years (averaged, 4.5 years ). Twenty patients in group I got
      an excellent results and 6 good; 9 patients in group II got an excellent results,
      7 good and 3 bad. Three patients in group II had recurrence of acromioclavicular
      joint dislocation. The long-term therapeutic effects of group I was better than
      that of group II. CONCLUSION: After clavicular hook plate implantation in
      treating type Tossy III dislocation of the acromioclavicular joint in young
      patients, it was necessary to use acromiocoracoid ligament transfer to repair
      coracoclavicular ligament and acromioclavicular ligament, which can improve the
      stability of acromioclavicular joint to prevent dislocation recurrence.

PMID- 23115991
TI  - [Abdominal random single pedicled flap of three leaves for the treatment of
      multiple finger skin defects].
AB  - OBJECTIVE: To discuss the effect of abdominal random single pedicled flap of
      three leaves for skin defects construction of the ends of several fingers.
      METHODS: From March 2005 to October 2010, 30 patients (90 fingers) with skin
      defects of the ends of several fingers were treated by abdominal random single
      pedicled flap of three leaves, including 20 males (60 fingers) and 10 females (30
      fingers) with an average age of 36 years old ranging from 15 to 56 years. The
      degloving injury or transverse defect of distal phalanx were treated with
      abdominal random single pedicled flap of three leaves. Postoperative survival of
      skin flap, flap shape, complications were observed, and the static two-point
      discrimination of flap were determined. RESULTS: All patients were followed up
      for 12.6 mouths in average. All the flaps survived. The color, texture and shape
      of the flaps were good. The static two-point discrimination was 5 to 10 mm. The
      function of the hands recovered satisfactory. CONCLUSION: The method of abdominal
      random single pedicled flap of three leaves has the advantages of simple, safe
      and less trauma for the donor site. The effect is satisfatory for skin defects
      construction of the ends of several fingers.

PMID- 23115992
TI  - [Finite element analysis of lumbar pelvic and proximal femur model with simulate
      lumbar rotatory manipulation].
AB  - OBJECTIVE: To study the changes of displacement and stress in the model of lumbar
      pelvic and proximal femur during lumbar rotatory manipulation. METHODS: The date
      of lumbar pelvic and proximal femur CT scan by Mimics 10.01 software was
      established a lumbar pelvic and proximal femur geometric model, then the model
      was modified with Geomagic 9, at last the modified model was imported into
      hypermesh 10 and meshed with tetrahedron, at the same time,add disc and
      ligaments. According to the principle of lumbar rotatory manipulation,the lumbar
      rotatory manipulation were decomposed. The mechanical parameters assigned into
      the three-dimensional finite element model. The changes of displacement and
      stress in the model of lunbar pelvic and proximal femur under the four conditions
      were calculated with Abaqus model of Hypermesh 10. RESULTS: 1) Under the same
      condition,the displacement order of lumbar was L1>L2>L3>L5 L5, anterior column >
      middle column > posterior column. 2) Under the different conditions, the
      displacement order of lumbar,case 3>case 1>case 4>case 2. 3) Under the same
      conditions, the displacement order of lumbar inter-vertebral disc from L1,2 to
      L5S1 was L1,2>L2,3>L3,4>L4,5>L5S1, as for the same inter-vertebral disc, the
      order was: second quadrant>third quadrant>first quadrant>fourth quadrant. 4)
      Under the different conditions,the displacement order of the inter-vertebral disc
      was L1,2>L2,3>L3,4>L4,5>L5S1, but to same inter-vertebral disc: case 3>case
      4>case 1 >case 2. 5) There were apparent displacement and stress concentration in
      pelvis and hip during the manipulation. CONCLUSION: 1) The principles of lumbar
      rotation manipulation closely related to the relative displacement caused by
      rotation of various parts of lumbar pelvic and proximal femur model; 2) During
      the process of lumbar rotatory manipulation, the angle of lateral bending and
      flexion can not be randomly increased; 3) During the process of lumbar rotatory
      manipulation, all the conditions of lumbar pelvic and proximal femur must be
      considered to determine indications and contraindications.

PMID- 23115993
TI  - [Proliferation, differentiation and BMP-2 expression of osteoblasts cultured in
      the plane under suitable electrical stimulation].
AB  - OBJECTIVE: To observe proliferation and differentiation of osteoblasts cultured
      in the plane on appropriate electrical stimulation, to specify whether it promote
      the proliferation, and observe expression of BMP-2 on electrical stimulation.
      METHODS: Osteoblasts were extracted from the skull of rabbit offspring and
      cultured. Cells after the 2nd generations were cultured. In experimental group,
      cells had electrical stimulation, and same stimulation time and intensity were
      given. In control group cells had not electrical stimulation. The proliferation
      and differentiation were detected at different time, and BMP-2 protein expression
      was analyzed. RESULTS: The cell morphology of experimental group in 8 days under
      the light microscope was observed and showed a lot of proliferation of
      osteoblasts, pleomorphic changes, in 6 to 8 days a small amount of Calcified
      spots was also observed; while in the control group, proliferation was slower.
      Differentiation of the experimental group was significantly, alkaline phosphatase
      staining and calcium nodules were positive, quantitative analysis of alkaline
      phosphatase increaseed significantly. Experimental group showed that BMP-2 was
      gradually increased by immunohistochemistry analysis. CONCLUSION: Electrical
      stimulation can promote the proliferation and differentiation of osteoblasts and
      achieved the increasement the number of cells in short-term, intracellular
      staining by immunohistochemistry showed the increasement in expression of BMP-2.

PMID- 23115994
TI  - [Replantation of the left severed lower limb on superior position: a case
      report].

PMID- 23115995
TI  - [Anatomic study of lower cervical spinous process for laminar screw fixation].
AB  - OBJECTIVE: To measure anatomic data of spinous process and vertebral plate and
      evaluate the possibility of fixation of spinous process and vertebral plate.
      METHODS: Twenty cadaveric cervibal spines of C3-C7 were dissected to expose
      vertebral plate and spinous process, and were measured by two methods, one was
      manual measured using digital caliper and the other was computed tomography
      scaning. Parameters were measured manually including vertebral plate height and
      width. The screw was inserted from the boundary of the vertebral plate and
      spinous process, and gone out from the top of vertebral plate back of opposite
      side. Then through the CT reconstruction, angle of screw insertion, length of
      screw trajectory and distance between the screw tip and vertebral artery and
      spinal cord were measured. Additionally, spinous process width and vertebral
      plate thickness of 100 patients' CT scans of C3-C7 cervical segment were measured
      to evaluate possibility of screw insertion at spinous process and vertebral
      plate. RESULTS: The screw fixation of lower cervical spinous process and
      vertebral plate were successfully placed,without impingement of spinal cord and
      vertebral artery. There was no statistic difference on the data of lamina height
      and width of 20 cadaver specimens between manual and CT measurements (P>0.05).
      Height and width of vertebral plate was (12.4 +/- 1.2) to (13.7 +/- 1.3) mm and
      (4.5 +/- 0.9) to (5.4 +/- 1.1) mm respectively and increased gradually from C3 to
      C7 (P<0.05). The trajectory length was (13.7 +/- 1.2) to (15.8 +/- 1.8) mm and
      increased gradually from C3 to C7 (P<0.05). The distance between screw tip and
      vertebral artery and spinal cord was (20.1 +/- 2.7) to (25.8 +/- 2.9) mm and (4.1
      +/- 1.8) to (5.0 +/- 1.2) mm respectively. The angles of screws insertion were
      (73.0 +/- 9.9) degrees to (85.3 +/- 10.1) degrees in the axial plane (P>0.05).
      Based on the CT measurements of 100 patients,the data of the spinous process
      width and lamina thickness varied from a minimum of (8.5 +/- 1.1) mm and (4.3 +/-
      0.5) mm for the C4, to a maximum of (14.5 +/- 2.0) mm and (6.0 +/- 1.1) mm for
      the C7 respectively. CONCLUSION: Lower cervical spinous process and vertebral
      plate screw fixation is feasible, which is a safe and stable screw approach for
      spinous process and vertebral plate fixation.

PMID- 23115996
TI  - [Thumb replantation through bridging ulnar proper digital artery and dorsal
      carpal branch of radial artery].
AB  - OBJECTIVE: To introduce treatment method of replantation of severed thumb trauma
      with proximal arterial, and to evaluate its efficacy. METHODS: From February 2007
      to March 2009,13 patients with severed thumb in serious injury of proximal
      arterial were treated with vein graft of volar forearm,bridging between dorsal
      carpal branch of radial artery on nasopharyngeal fossa and distal stump of ulnar
      proper digital artery. Among them, there were 11 males and 2 females with an
      average age of 34.5 years ranging from 16 to 50 years. Seven cases were in the
      left thumb,6 in the right thumb. Eight cases were complete separation, incomplete
      separation in 5 cases. Ten cases recieved emergency reimplantation, 3 cases with
      the arterial crisis after conventional replantation were explorated and repaired.
      RESULTS: Thumb of 13 cases all survived. All patients were followed-up for 8 to
      17 months (averaged, 11 months). Replantation thumb obtained satisfactory
      appearance. According to Chinese Medical Association Society of Hand Surgery
      Trial criteria, the results were excellent in 9 fingers, good in 3 fingers, 1
      poor finger. Two point discrimination of finger pulp was 5 to 8 mm (averaged 6.5
      mm). CONCLUSION: By repairing artery of thumb with vein graft of volar forearm,
      bridging between dorsal carpal branch of radial artery on nasopharyngeal fossa
      and distal stump of ulnar proper digital artery,complex severed thumb replants on
      surgery position comfortable,without affecting the blood supply of the hand,
      expanding the indications for replantation and improving the success rate of
      replantation.

PMID- 23115997
TI  - [Treatment of proximal radius epiphyseal injuries of O'Brien type III with
      titanium elastic nail in children].
AB  - OBJECTIVE: To investigate the feasibility and clinical effects of titanium
      elastic nail (TEN) for treatment of proximal radius epiphyseal injuries of
      O'Brien type III. METHODS: From October 2008 to November 2009,19 patients with
      proximal radius epiphyseal injuries of O'Brien type III were treated with
      internal fixation, including 13 males and 5 females with an average age of 8.3
      years old ranging from 6 to 12 years. The average time from injury to surgery was
      3.5 days (2 to 7 days). The reduction situation after operation was assessed by
      Metaizeau criteria, and the elbow function after operation were evaluated by
      Broberg-Morrey elbow score. RESULTS: All patients were followed-up for 8.7 months
      in average (ranged 6 to 12 months). No infection, TEN brokage, skin bursting and
      other complications occurrenced. According to Metaizeau criteria, the results
      were excellent in 7 cases, good in 10 cases and fair in 2 cases. The Broberg
      Morrey score rose from preoperative (47.3 +/- 5.1) to (86.6 +/- 6.3) at 3 months
      followed-up (t=139.17, P=0.0002); the outcome was excellent in 7 cases, good in 9
      cases, and fair in 3 cases. CONCLUSION: Internal fixation with TEN in treatment
      of proximal radius epiphyseal injuries of O'Brien type III has a limited
      invasion, cosmetic beauty, safety and reliability advantages. This technique
      provides a reliable alternative in proximal radius epiphyseal injuries of O'Brien
      type III.

PMID- 23115998
TI  - [Traumatic dislocation of superior tibiofibular joint].
AB  - OBJECTIVE: To explore the characteristics, diagnosis and treatment on traumatic
      dislocation. METHODS: From April 2000 to August 2010, 12 patients with acute
      traumatic dislocation of superior tibiofibular joint were treated including 10
      males and 2 females with an average age of 30.6 years old ranging from 18 to 60
      years. According to Ogden classification, 8 cases were the anterolateral
      dislocation, 2 were posterior-medial dislocation, and 2 were upward dislocation.
      All patients had swelling in lateral-inferior of knee, fibular head prominent,
      fibular head pain, floating feeling in head of fibula. One case was treated by
      conservative treatment, and the remaining 11 cases by surgical treatment.
      RESULTS: All patients were followed-up for 10 months to 3 years (means 18
      months). Evaluation by Lysholm scoring,the total scores were 95.08 +/- 2.02,
      involving limbing 4.92 +/- 0.28, support 4.92 +/- 0.28, interlocking 15.00 +/-
      0.00, instability 24.58 +/- 0.79, pain 22.50 +/- 1.24, swell 8.50 +/- 0.90,
      climbing stairs 9.75 +/- 0.62, squatting 4.92 +/- 0.28; 11 cases achieved
      excellent results and 1 good. Nerve functional recovered. X-ray was no longer
      dislocation. CONCLUSION: The diagnosis of traumatic dislocation is easy
      misseddiagnosis, surgery is the main treatment method, the prognosis is good.

PMID- 23115999
TI  - [Manipulative reduction of shoulder lift for the treatment of posterior
      dislocation of hip joint].
AB  - OBJECTIVE: To observe the effects of shoulder lift reduction for treatment of
      posterior dislocation of hip joint. METHODS: From July 2001 to June 2010, 14
      cases of posterior dislocation of hip joint were treated with shoulder lift
      reduction involving 12 males and 2 females with an average age of 34.6 years
      ranging from 18 to 57 years. After recduction, all patients were assisted with
      the traction, exercise and traditional Chinese medicine. The mean duration
      between injured and treatment was 1.1 days (2 hours to 3 days). According to
      Harris scoring system the hip joint function were evaluated. RESULTS: All
      patients were followed-up for 8 to 24 months (means 16 months). Fourteen cases
      were reset well in first without any complication. The Harris score was (97.14 +/
      4.90) in total, involving hip pain (42.86 +/- 1.88), articular activity (4.71 +/
      0.47), daily activity (45.57 +/- 9.26), deformity (4.00 +/- 0.00), the clinical
      outcome was excellent in 12 cases,good in 2. There were not complications such as
      avascular necrosis of the femoral head, and so on. CONCLUSION: The shoulder lift
      reduction can be used by one person, and the treatment of posterior dislocation
      of hip joint is effective. It established a good foundation for the
      rehabilitation of trouble hip.

PMID- 23116000
TI  - [A case report of osteochondroma in the lateral calcaneus].

PMID- 23116001
TI  - [Mechanism of weightlessness osteoporosis and preventive and therapeutic effect
      of traditional Chinese medicine].
AB  - Weightlessness environment can lead to the muscle atrophy and body fluid
      distribution upward,which can cause the bone calcium metabolism disorder and
      always accompanied by the loss of bone microstructure and increased rate of bone
      fracture. Under microgravity,the astronauts are much easier to decrease the Ca2+
      ion in bone, which can cause serious osteoporosis. However the bone lost is not
      equilibrium, it is especially serious in the mechanism loading bone and the
      recovery process is more difficult. These are very different from the
      osteoporosis in older people and postmenopausal osteoporosis. It is necessary to
      find an optimal method to due with it. In traditional Chinese medicine theory,the
      kidney stores "Jing" and dominates the bone, thus a lot of bone related diseases
      can be treated through the kidney. A lot of clinical practices have also proved
      that the Chinese herbs used under the guidance of basic Chinese medicine theory
      are always good at the treatment of common osteoporosis. In simulated
      weightlessness experiment, people found that the kidney nourishment drugs do can
      prevent the decrease of BMD. So in this article we want to review the causes of
      weightlessness and the potentials applications of tradition Chinese medicine in
      the treatment of weightlessness osteoporosis.

PMID- 23116002
TI  - [Treatment of early stage avascular necrosis of the femoral head].
AB  - Avascular necrosis is a progressively devastating disease and primarily affects
      weight-bearing joints. The hip is the most commonly affected joint. In early
      stage, nonoperative (including pharmacologic intervention and biophysical
      treatments) and operative modalities for protecting hip joint have become the
      main therapeutic methods. However there is still no satisfied mothod with
      reasonable effect. According to the treatment of the avascular necrosis of the
      femoral head of the pre-collapse stage, core decompression with modification of
      technique is still one of the safest and most commonly employed procedures.
      Recently there have been attempts to enhance the effect of core decompression
      with use of various growth and differentiation factors. Which is the hot spot of
      current research. Early diagnosis is the key to the treatment of the avascular
      necrosis of the femoral head. Comprehensive treatment which is based on the core
      decompression is still the main treatment of today.

PMID- 23116003
TI  - [Viewpoint on standard usage of the term of "head of radius" and "capitulum
      radius"].

PMID- 23116004
TI  - Comparative evaluation of herbs and spices against bacterial pathogens.

PMID- 23116005
TI  - Making progress: considering standards of care.

PMID- 23116006
TI  - Drug delivery to the eye: current trends and future perspectives.

PMID- 23116007
TI  - Nitric oxide-releasing nanoparticles: challenges and future prospects.

PMID- 23116008
TI  - Thermal-sensitive hydrogels as nasal vaccine delivery systems.
AB  - The National Key Laboratory of Biochemical Engineering established in 1995 is
      affiliated with the Institute of Process Engineering, Chinese Academy of Sciences
      (CAS), and located in Zhong-guan-cun (Beijing, China). The National Key
      Laboratory of Biochemical Engineering is working towards developments in the
      fields of bio-reaction, bioseparation and bio-formulation, by chemical and
      material methods. Over the last 5 years, approximately 200 scientists and
      students have worked at the laboratory, and published over 400 articles. Numerous
      universities, companies and institutes have established cooperative relationships
      with this laboratory, and over 70 cooperative research programs with other
      researchers have been conducted in the past few years.

PMID- 23116009
TI  - Electrospun hybrid nanofibers doped with nanoparticles or nanotubes for
      biomedical applications.
AB  - Electrospinning is a powerful technique to produce fibers with a diameter ranging
      from tens of nanometers to several micrometers. Compared with single-component
      nanofibers, composite or hybrid nanofibers are promising due to the unique
      properties possessed by both the host and the guest materials. Doping
      nanoparticles (NPs) or nanotubes (NTs) have excellent optical, mechanical,
      electrical or catalytic properties within polymer nanofibers, which makes it
      possible to produce functional nanofibers with promising applications. In this
      review, followed by a brief introduction of basic theory of electrospinning
      techniques, we give a literature survey of the NP- or NT-doped electrospun
      polymer nanofibers in terms of the producing methods and potential applications
      in the fields of tissue engineering, wound dressing and drug-delivery systems.
      Some of the aspects related to the improved protein adsorption capability,
      mechanical durability and, thus, improved cell attachment and proliferation of
      the NT-doped polymer nanofibers, as well as the significantly decreased burst
      release profile of the NT-doped polymer nanofibers used as drug-delivery systems
      are discussed.

PMID- 23116010
TI  - Multivalent ligand: design principle for targeted therapeutic delivery approach.
AB  - Multivalent interactions of biological molecules play an important role in many
      biochemical events. A multivalent ligand comprises of multiple copies of ligands
      conjugated to scaffolds, allowing the simultaneous binding of multivalent ligands
      to multiple binding sites or receptors. Many research groups have successfully
      designed and synthesized multivalent ligands to increase the binding affinity,
      avidity and specificity of the ligand to the receptor. A multimeric ligand is a
      promising option for the specific treatment of diseases. In this review, the
      factors affecting multivalent interactions, including the size and shape of the
      ligand, geometry and an arrangement of ligands on the scaffold, linker length,
      thermodynamic, and kinetics of the interactions are discussed. Examples of the
      multivalent ligand applications for therapeutic delivery are also summarized.

PMID- 23116011
TI  - Developing nanotherapies for neurodegenerative diseases: ORMOSIL and its
      potential in axonal transport.
AB  - In neurons, essential components packaged into vesicles are transported down
      microtubules to the ends of axons (synapses) where they are utilized. Components
      are also transported from the synapse to the cell body. This transport pathway is
      crucial for normal development, cell survival and plasticity. Recent work has
      established that defects in transport can contribute to the initiation of
      neurodegenerative disease, culminating in cell death and degeneration. Thus,
      delivering therapeutic treatments to an early defect is critical since many
      current strategies target pathology that occurs at later stages in the disease.
      Current treatments also affect the entire organism, causing side-effects that are
      often more deleterious than the disease. This article discusses how engineered
      synthetic structures can be used to directly target axonal transport--a pathway
      that is affected during the early stages of disease. Studies in this area will
      require the exchange of fundamental knowledge between biologists, chemists and
      engineers to effectively manufacture novel biomaterials for medical use.

PMID- 23116012
TI  - Ultrasound and microbubble-assisted gene delivery: recent advances and ongoing
      challenges.
AB  - Having first been developed for ultrasound imaging, nowadays, microbubbles are
      proposed as tools for ultrasound-assisted gene delivery, too. Their behavior
      during ultrasound exposure causes transient membrane permeability of surrounding
      cells, facilitating targeted local delivery. The increased cell uptake of
      extracellular compounds by ultrasound in the presence of microbubbles is
      attributed to a phenomenon called sonoporation. Sonoporation has been
      successfully applied to deliver nucleic acids in vitro and in vivo in a variety
      of therapeutic applications. However, the biological and physical mechanisms of
      sonoporation are still not fully understood. In this review, we discuss recent
      data concerning microbubble--cell interactions leading to sonoporation and we
      report on the progress in ultrasound-assisted therapeutic gene delivery in
      different organs. In addition, we outline ongoing challenges of this novel
      delivery method for its clinical use.

PMID- 23116013
TI  - Recent advances in the rational design of silica-based nanoparticles for gene
      therapy.
AB  - Gene therapy has attracted much attention in modern society and provides a
      promising approach for treating genetic disorders, diseases and cancers. Safe and
      effective vectors are vital tools to deliver genetic molecules to cells. This
      review summarizes recent advances in the rational design of silica-based
      nanoparticles and their applications in gene therapy. An overview of different
      types of genetic agents available for gene therapy is provided. The engineering
      of various silica nanoparticles is described, which can be used as versatile
      complexation tools for genetic agents and advanced gene therapy. Several
      challenges are raised and future research directions in the area of gene therapy
      using silica-based nanoparticles are proposed.

PMID- 23116014
TI  - [Experience of use of prolit septo in the complex treatment of patients with
      urolithiasis].
AB  - The efficacy of phytogenic drug prolit septo in the complex treatment of patients
      with urolithiasis complicated by infectious-inflammatory process was evaluated.
      The effects of prolit septo were assessed by a comparative evaluation of the
      results of microbiological analysis of urine in 14 patients of main group and 12
      patients of control group. Patients in both groups were matched by sex, age, and
      results of raiological, clinical, biochemical and microbiological methods of
      examination. For the treatment of 11 patients of the main group, prolit septo was
      applied in combination with standard anti-bacterial treatment, 3 patients
      received monotherapy with prolit septo within 3-6 weeks. The drug was
      administered at a dose of 1200 mg (2 capsules) 3 times a day. Twelve patients of
      the control group received only standard treatment. The duration of treatment in
      both groups was 1-2 weeks. It was found that combined therapy with prolit septo
      is more effective than standard antibacterial treatment. Against the background
      of combined therapy the disappearance of bacteriuria was noted in 54.5% of
      patients of main group compared with 8.3% of patients of control group.

PMID- 23116015
TI  - [Comparative effectiveness of fluoroquinolones and beta-lactams in the complex
      therapy of patients with chronic pyelonephritis].
AB  - A comparative study has evaluated the effect of fluoroquinolones and beta-lactams
      on clinical and biochemical manifestations of chronic pyelonephritis (CPN). 108
      patients aged from 18 to 59 years (mean age - 40.26 +/- 10.09 years) with
      secondary CPN against dysmetabolic nephropathy and nephrolithiasis in a phase of
      active inflammation were observed. The majority of patients were women - 89
      (82.4%). CPN was diagnosed in accordance with the N.A. Lopatkin and V.E. Rodoman
      clinical classification (1974) based on results of complete clinical and
      laboratory, radiologic and ultrasound examinations. Special methods of
      investigation included determination of the activity of lipid peroxidation,
      antioxidant system and the structural parameters of the cell membrane
      ofpolymorphonuclear leukocytes (PMN). Pain, dysuria, and intoxication syndrome
      were arrested in all patients after 14 days of therapy. The high efficacy was
      reported for patients treated with sparfloxacin. A similar trend was observed in
      the dynamics of intoxication syndrome regression. In addition, there was a
      significant reduction of lipid peroxidation products and an increase of alpha
      tocopherol in the PMN membranes; the content of phospholipids significantly
      increased and cholesterol level declined during the treatment. The results showed
      that use of fluoroquinolones and the B-lactams in the treatment of patients with
      CPN against the nephrolithiasis leads to a significant relief of clinical
      symptoms of the disease, as well as to restoration the structural and functional
      state of PMN membranes. The most distinct and early clinical-laboratory effect
      was obtained against the background of use of fluoroquinolone sparfloxacin.

PMID- 23116017
TI  - [Endovascular treatment of persistent dysuria and chronic pelvic pain in women
      with pelvic varicose veins].
AB  - The results of the examination and treatment of 16 patients aged from 26 to 46
      years with persistent urinary disorders and chronic pelvic pain due to severe
      pelvic varicose veins are presented. Using ultrasound with color Doppler mapping
      and venography of renal and ovarian vein for evaluation of condition of the
      venous system of the pelvis, the significant dilation of the internal iliac,
      ovarian and uterine veins with a pronounced decrease in blood flow in veins up to
      the stasis of blood, accompanied by flow turbulence and powerful backflow of
      renal blood through ovarian veins were found in all patients. According to
      uroflowmetry, there was a decrease in detrusor tone and a violation of evacuation
      capacity of the bladder. Evaluation of microcirculation using LDF allowed to
      diagnose congestive hemodynamic type of microcirculation. Scleroembolization for
      varicose ovarian vein with Gianturco coil and ethoxysclerol was performed in all
      patients. Positive therapeutic effect in the form of eliminating varicose pelvic
      veins, pain relieve, disappearance of persistent dysuria, and the remission of
      chronic cystitis was achieved in 86% of women. This intervention provided the
      normal outflow of blood from the pelvic veins, contributed to the normalization
      of uroflowmetry data and restoration of normal microcirculation in the urinary
      bladder.

PMID- 23116016
TI  - [Stages of diagnosis and surgical treatment for combined bladder injuries].
AB  - 62 case histories of patients with bladder injuries who were admitted in the
      Department of Urology and Emergency Surgery of the Republican Scientific Center
      of Emergency Medicine (RRCEM) from 2001 to 2010 were retrospectively analyzed. 15
      (24.2%) patients with hematuria or urethremorrhagia were admitted in the
      emergency room within an hour after the injury onset. Three (4.8%) patients were
      hospitalized in the period 1-3 h since injury onset, 12 (19.3%) patients since 3
      6 hours, 5 (8.1%) - since 6 to 12 h, 16 (25 8%) patients - since 12 to 24 hours,
      and 11 (17.7%) patients - after 24 hours. Concomitant injury of the bladder with
      fractures of the pelvic occurred in 21 (33.8%) cases. At the time of admission in
      the emergency room, I-II degree traumatic shock was diagnosed in 37 (60%) of
      patients, III-IV degree traumatic shock - in 11 (17,7%). All 62 patients had a
      complete rupture of the bladder, 37 (59.6%) of patients had intraperitoneal
      rupture, 23 (37.1%) - extraperitoneal rupture, and only 2 (3.3%) - mixed rupture.
      Strict adherence to the RRCEM algorithm of diagnosis and treatment of patients
      with bladder injuries have substantially improved the efficiency of complex of
      medical and diagnostic measures and improved the outcomes of this group of
      patients - mortality was 12.9%.

PMID- 23116018
TI  - [The use of tolterodine in patients with recurrent chronic cystitis].
AB  - The article presents the results of evaluation of effect of M-cholinoblocer
      tolterodine on the symptoms of lower urinary tract diseases (LUTD) and quality of
      life of patients with recurrent chronic cystitis. The study included 47 patients
      with chronic recurrent cystitis at acute stage with non-obstructive type of
      urination and LUTS. Group 1 included 23 women aged 45 to 56 years, who received
      tolterodine on the background of antibacterial therapy, taking into account the
      sensitivity of the isolated strain. Control group included 24 patients who
      received standard antibacterial therapy, also taking into account the sensitivity
      of the pathogen, and spasmolytics. The groups were almost homogeneous and did not
      differ on the basic characteristics. Analysis of the results of the study showed
      that tolterodine as a symptomatic therapy can reduce the time of rehabilitation.
      Therapy with tolterodine has shown clinical efficacy for 85.7% of women, has
      improved the quality of life by 24.8% compared with the control group, and
      provided relief of urgent and irritative symptoms in the short time.

PMID- 23116019
TI  - [Water and electrolyte metabolism disturbances in patients with metabolic
      syndrome].
AB  - Taking into account the high prevalence of renal disease in metabolic syndrome
      (MS), relationship between the reduction of the renal function and severity of
      disorders of lipid metabolism and increased risk of cardiovascular complications,
      evaluation of electrolyte and nitrogen metabolism was performed for 112 patients
      with MS. In addition, serum levels ofaldosterone, adrenocorticotropic hormone,
      neutrophil gelatinase-associated lipocalin, cortisol, beta2-microglobulin,
      vasopressin, and level of microalbumin in urine were assessed. MS patients showed
      a reduction of the daily expression of the main osmotically active substance -
      urea, potassium, sodium and chloride. The increased production of antidiuretic
      hormone and related water retention, increased microalbumin excretion, indicating
      the development of systemic endothelial dysfunction and glomerular
      hyperfiltration, were detected. Reported violations are developing by type of
      "vicious circle": fluid retention leads to hyperfiltration, renal dysfunction
      exacerbates water-electrolyte disorders.

PMID- 23116020
TI  - [Effect of acute operational stress on the exchange of biogenic amines in
      prostate gland and steroidogenesis (experimental study)].
AB  - Patterns of metabolic imbalance of biogenic amines in the tissue of the prostate,
      leading to violations of hemodynamics and trophism, were revealed in experimental
      study on laboratory animals. At the same time the stress was acute inducer of
      functional testosterone deficiency, which persisted throughout the observation
      period. Based on experimental data obtained, pathogenetic role of stress-induced
      metabolic imbalance of biogenic amines and steroidogenesis as possible early
      pathophysiological mechanisms of prostate diseases in humans is proved.

PMID- 23116021
TI  - [Neurophysiologic evaluation of patients with chronic prostatitis (III B chronic
      pain syndrome)].
AB  - The article presents the results of neurophysiological examination of 32 patients
      with noninflammatory form of abacterial chronic prostatitis/ chronic pelvic pain
      syndrome (CP/CPPS III B). Intramuscular electromyography was performed, right and
      left bulbocavernous reflex and cortical somatosensory evoked potentials during
      stimulation of n. pudendus were evaluated. It is shown that there is a high
      frequency of abnormal neurophysiological patterns in the absence of clinical
      neurological disease in patients with CP/CPPS III B. In this case, the pain as
      the main symptom was not associated with prostate disease. It is suggested that
      some patients with a diagnosis of CP/CPPS III B have neurological pathology that
      not manifested at the time of the examination.

PMID- 23116022
TI  - [Chronic infection urethroprostatit: a new look at old problem].
AB  - An open, short-term, prospective, randomized study was conducted. 114 men with
      chronic urethroprostatitis against chlamydial-mycoplasmal infection, mean age
      41,2 +/- 0,4 years, were observed. Follow investigations were performed: PCR,
      microscopic examination of urethral secretions and semen, transabdominal and
      transrectal ultrasound examination of prostate, evaluation of indicators of local
      and systemic immunity. In patients with chronic urethroprostatitis, abnormal
      urethral secretions were dominated; according to data of ultrasound examination,
      changes in the prostate were registered in all patients, as well as disturbances
      in cellular and humoral immunity. Depending on the method of treatment, patients
      were divided into two groups: Group 1 received an immunomodulator Lavomax and
      basic treatment: azithromycin at a dose 1.0 g once a week for 3 weeks, Celebrex,
      physiotherapy (low-intensity laser radiation), prostate massage; and Group 2
      received only basic therapy. The control group consisted of 30 healthy men. The
      most pronounced normalization of cellular immunity (decreased number of
      leukocytes, reduction of lysosomal activity, increased activity and intensity of
      phagocytosis, and functional reserve of neutrophils in the ejaculate), as well as
      normalization of lymphocyte subpopulation composition, immunoregulatory index in
      the peripheral blood, and levels of IgA, IgG, IL-8, INF-gamma, resolution of
      clinical symptoms were observed among patients in Group 1. Moreover, the rate of
      elimination of infectious agents was significantly higher in Group 1. Thus, the
      use of immunomodulator Lavomax is pathogenetically substantiated treatment for
      chronic urethroprostatite against chlamydial and mycoplasmal infection, which
      allows to include Lavomax in a comprehensive treatment of this disease.

PMID- 23116023
TI  - [Effect of prostatilen AC suppositories on course of experimental prostatitis].
AB  - The article presents the results of evaluation of efficacy of new drug
      prostatilen AC (rectal suppositories), containing regulatory peptides of the
      bovine prostate and zinc arginate-glycinate complex, in the treatment of
      prostatitis. The experiment was conducted on 40 Sprague-Dawley rats weighing 180
      200 g. Chronic prostatitis was modeled by injection of 10% Dimexidum in
      combination with water, mixed with turpentine, a volumetric ratio of 4:1. It is
      shown that prostatilen AC has pronounced organotropic antiinflammatory effect,
      which manifests in reducing the weight of the prostate, reducing the protein
      level in the urine, activity of acid phosphatase, and levels of ceruloplasmin and
      C-reactive protein. In addition, this drug normalizes the act of urination and
      increases the diurnal diuresis, has antioxidant properties and increases the
      blood level of the male sex hormone testosterone.

PMID- 23116024
TI  - [Immediate and long-term results of nephrectomy with inferior vena cava
      thrombectomy in renal cell carcinoma].
AB  - Results of treatment of 32 patients after nephrectomy with thrombectomy for renal
      cell carci-noma complicated by tumor thrombosis of the inferior vena cava were
      analyzed. The study in-cluded patients only with II - IV clot levels: 26 patients
      with T3b - the length of the thrombus 5.1 +/- 1.75 cm, 6 patients with T3c - the
      length of a thrombus - 14.8 +/- 0.98 cm. One patient (3.1%) died due to pulmonary
      artery thromboembolia in immediate postoperative period. 1-2 degrees Clavier
      Complications were observed in 11 patients, 3-4 degree - in two (6.2%) patients.
      90.4% of patients had metastases in distant organs and (or) in the regional lymph
      nodes, which nega-tively affected the survival rates of patients - 5-year
      survival rate was 36%. The presence of lymphogenous metastases, MSKCC criteria
      were factors affecting survival rate. Survival rates of patients with T3b and T3C
      levels were not statistically different. The results of postoperative systemic
      targeted therapy were significantly statistically better than the results of
      immunotherapy.

PMID- 23116025
TI  - [Supine percutaneous nephrolithotripsy].
AB  - MATERIALS AND METHODS: The report included the results of PNL in 64 patients. In
      34 of patients (Group I), the surgery was performed in the prone position, and in
      30 patients (Group II) - in semilateral (supine) position. The study included
      patients with one or more pelvic stones larger than 2.5 cm and requiring only a
      single percutaneous approach, with a body mass index less than 30 kg/m2 and the
      absence of contraindications to the PNL in the prone position. Average size of
      stones was 3.2 cm in Group I, and 3.0 cm in Group II. For the comparative
      analysis between the two groups, timing of surgery, intra- and postoperative
      complication rates, extent of blood loss and length of hospital stay were
      evaluated. RESULTS: Analysis of the results of PNL performed in prone and supine
      position of patient showed the absence of statistically significant difference in
      the effectiveness of the surgery, extent of blood loss, and length of hospital
      stay between the two groups. Significant difference was observed only in the
      timing of surgery (Group I, 68 min; Group II, 43 min). CONCLUSION: When
      performing PNL in patients with uncomplicated nephrolithiasis in prone and supine
      position of patients on the operating table, significant difference was observed
      only in the timing of surgery.

PMID- 23116026
TI  - [Modified method of retropubic prostatectomy (RMAPE method)].
AB  - The article presents the results of the examination and treatment of 125 patients
      with benign prostatic hyperplasia who underwent surgery in the urological clinic
      of RMAPE. Retropubic adenomectomy according to the method proposed by the Clinic
      of Urology and Surgical Andrology of RMAPE was performed in 83 patients, and 42
      patients underwent transvesical adenomectomy. In accordance with a number of
      parameters (timing of surgery, frequency of intra- and postoperative
      complications, extent of blood loss, duration of bladder drainage, length of
      hospital stay), a modified method of retropubic prostatectomy demonstrated
      significantly better results than transvesical adenomectomy.

PMID- 23116027
TI  - [On the question of the so-called gold standard of surgical treatment of benign
      prostatic hyperplasia].
AB  - The article presents the comparative analysis of results of surgical methods used
      for the treatment of patients with BPH. The standardization of surgical TURP
      interventions as the "gold standard" in comparison with transvesical
      extraurethral adenomectomy is estimated. After TURP, according to the data from
      domestic and foreign authors, taking into account own author's data,
      complications develop in 28.7 to 100% cases after non-radical removal of
      adenomatous (hyperplastic) tissue, and only in 5.6% of cases after radical
      extraurethral prostatectomy. Thus, open transvesical or retropubic extraurethral
      adenomectomy is considerably superior to "closed" transurethral resection of the
      prostate as consistent with immediate and long-term results.

PMID- 23116028
TI  - [Combination treatment of subtotal epispadias].

PMID- 23116029
TI  - [Experience of invasive surgical treatment of renovascular hypertension in
      children].

PMID- 23116030
TI  - [Optimization of the use of phosphodiesterase-5 inhibitors].

PMID- 23116031
TI  - [Prevention of recurrent lower urinary tract infections--a view from the past to
      the future].

PMID- 23116032
TI  - [Efficiency of vitaprost in patients with chronic prostatitis].

PMID- 23116033
TI  - [Necessity and safety of combined drug therapy in patients with urination
      disorders].

PMID- 23116034
TI  - [Classification and etiopathogenesis primary obstructive megaloureter in
      children].

PMID- 23116035
TI  - [Silodosin. From research to clinical application: the activity, safety and long
      term effectiveness].

PMID- 23116036
TI  - [Structural and functional shifts in the central nervous system due to ionizing
      radiation; human efficiency].
AB  - The article discusses the results of experiments with animals and medical
      hygienic and epidemiological evidence from the monitoring of health and
      efficiency of nuclear industry personnel started in the 1950s, as well as of high
      power gamma- and nuclear energetic sources in research centers. Also, data about
      health disorders and disability among Chernobyl cleanup workers were analyzed.
      Morphological deviations in the central nervous system in animals immediately
      after and in delayed periods following exposure to different doses and CT data
      about cerebral structural changes in cleanup workers are presented. Dependence of
      the functional disturbances in and morbidity among personnel shortly after and in
      delayed periods on dose value and dose rate are scrutinized closely.

PMID- 23116037
TI  - [Major results of research and development of heterogenous biocatalysts for
      regenerated water clearing from harmful admixture].
AB  - The biological method of clearing atmospheric condensate in pressurized habitats
      exploits filters with a heterogenic biocatalyst produced by way of immobilizing
      harmless for human, animal and plant microoganisms on water-insoluble solid
      carrier--foam polyvinyl-formal (FPVF), and a hydrogen peroxide biofilter
      containing triacetate cellulose-immobilized catalase. Experience of forming an
      immobilized bacterial association as a polyenzyme system is particularly
      promising for development of advanced biotechnologies. Biocatalysts with expanded
      applicability can be manufactured using a FPVF-immobilized associative bacterial
      culture composed of Paracoccus denitrificans, Pseudomonas esterophilus and
      Methilopila capsulata. In aerobic condition at room temperature the heterogenic
      biocatalyst is capable to transform harmful organics in atmospheric condensate,
      e.g. methyl amine, ethyl acetate, acetic acid, ethanol and acetone into the end
      products, i.e. carbon dioxide and water. Ammonia is consumed by 3 cultures as a
      source of nitrogen.

PMID- 23116038
TI  - [Research activities of cosmonauts in long-duration orbital missions].
AB  - The paper presents the view of space medicine and human factor experts on the
      problems of cosmonaut's research activities. Readiness of ISS crewmembers for
      conducting experiments and research equipment handling depends on the pre-flight
      training quality and course of adaptation to the flight conditions, the latter of
      particular criticality for participation in human use tests as an object.

PMID- 23116039
TI  - [Effects of damage and post-radiation reparation of cornea epithelium cells
      chromosomal apparatus in mice following irradiation by protons with the energy of
      25 MeV].
AB  - Damage and post-radiation reparation processes were studied in cornea epithelium
      cells of mice irradiated by protons with the energy of 25 MeV and 60Co gamma-rays
      singly and in 2 fractions. Protons linear energy transfer (LET) was equal to 2.1
      keV/microm, dose rate - 0.5 cGy/s. Animals were irradiated singly by 25 and 750
      cGy and doubly (25 + 25; 50 + 50; 125 + 125; 250 + 250 cGy) with a 24-hr
      interval. Investigations were performed in 24, 72 and 120 hrs. after single and
      in 24 hrs. after double irradiation. Preparations were analyzed with the anaphase
      technique. 25 MeV protons were shown to cause more severe damages to the
      chromosomal apparatus in mammal cells including dramatic suppression of cell
      division and profuse formation of cells with aberrant mitoses as compared with
      gamma-induced damages. Exchange-type aberrations were more frequent. There was a
      reliable decrease of the aberrant mitosis rate in consequence of fractionated
      irradiation by 25 MeV protons and gamma-rays. On passing 24, 72 and 120 hours,
      coefficients of relative biological effectiveness (RBE) of 25 MeV protons were
      equal to 1.4 +/- 0.2; 1.3 +/- 0.1; 1.2 +/- 0.1 for the mitotic index and 1.5 +/-
      0.1; 1.3 +/- 0.2; 1.1 +/- 0.1 for aberrant mitosis, respectively.

PMID- 23116040
TI  - [Direct proteomic profiling of human urine and blood serum in an experiment with
      5-day dry immersion].
AB  - Changes in proteome of urine and blood serum obtained from 14 healthy humans (age
      21-29 yrs) medically certified for an experiment with dry immersion were
      analyzed. Urine and serum samples were pre-fractionated and enriched with
      magnetic particles MB-WCX and MB-HIC, respectively, on robot ClinProt (Bruker
      Daltonics) for direct mass-spectrometry profiling by MALDI-TOF. As a result, 143
      protein peaks on the average were identified in urine samples. It was shown that
      a high variation coefficient in 23.7% of protein peaks, i.e. double technical,
      points to the most plastic fraction of the urine proteome. In blood serum, 175
      peaks were identified in a sample on the average. Comparison of baseline and
      immersion mass-spectra of the blood proteome revealed significant differences.
      Increased peak areas of several protein fragments--C3 and C4 fragments of
      complement system, high-molecular kininogen and fibrinogen--can be ascribed to
      human body adaptation to the experimental conditions.

PMID- 23116041
TI  - [Electron-microscopy analysis of the myocardium of rats developed in
      hypergravity].
AB  - The results of the quantitative electron-microscopy investigation of the left
      heart myocardium in rats continuously exposed to 2 G in the pre- and postnatal
      (75 days) ontogenesis evidence formation of a cardiac hystiocyte ultrastructure
      in support of the functioning of the left ventricle myocardium against
      chronically high blood weight. Mechanisms of the functional adaptation of cardiac
      hystiocytes to 2 G do not correspond to mechanisms observed by other authors in
      adult rats chronically exposed to hypergravity (2 G) which infers a better
      effectiveness of adaptation mechanisms formed in the course of pre- and postnatal
      ontogenesis.

PMID- 23116042
TI  - [Evaluation of the actoprotective action of a heteroaromatic antioxidant].
AB  - Experiments with mice showed that heteroaromatic antioxidant IBKhF-11
      (intraperitoneally 1 mg/kg) alters the main individual behavior characteristics
      in the open field test, lessens stress from running on treadmill, reduces oxygen
      consumption by 33-37% over 3 hours and decreases rectal temperature by 2.4
      degrees C at the most. In fact, IBKhF-11 stimulates the anaerobic pathway of
      energy production during physical work by increasing glucose level etc., and
      corrects shifts in such biochemical parameters of blood serum as total bilirubin,
      uric acid and triglycerides and enzyme activities. The low-toxicity compound
      (intraperitoneal injection of no more than 1500 mg/kg of LD50 on the average) has
      every potential to appear on the market in the form of performance enhancing
      drugs.

PMID- 23116043
TI  - [Automated analysis of bacterial preparations manufactured on automatic heat
      fixation and staining equipment].
AB  - Heat fixation of preparations was made in the fixation bath designed by EMKO
      (Russia). Programmable "Emkosteiner" (EMKO, Russia) was used for trial staining.
      Reagents set Micko-GRAM-NITsF was applied for Gram's method of staining. It was
      demostrated that automatic smear fixation equipment and programmable staining
      ensure high-quality imaging (1% chromaticity variation) good enough for
      standardization of Gram's staining of microbial preparations.

PMID- 23116044
TI  - [Methods of bio-engineering destruction of root residues in application to a
      space vitamin greenhouse with ionite artificial soil].
AB  - Regeneration of ionite artificial soil (AS) in root modules (RM) of conveyor-type
      space greenhouses should be proceeded by removal of root residues without
      disruption of the AS capillary-porous structure. The proposed method consists of
      two stages of root residues destruction. On the first stage, AS treatment by 0.7%
      an alkali water solution with added 0.7% hydrogen peroxide over 3.5 hours in a
      thermal-insulation container at 95 +/- 4 degrees C reduces root residue mass up
      to 60%. Specific energy cost of SHF pulses to maintain the required temperature
      is 1 W x hr for cleaning 1 g and AS sterilization from saprotrophs. On the second
      stage, AS undergoes saturation with a liquid anaerobic medium for 7-day
      cultivation of thermophilic Clostridium thermocellum at 55 degrees C. Seven days
      of bio-engineering regeneration enables removal of 90% root biomass. Residual
      products of fermentation have a stimulating effect on seed germination and
      subsequent plant growth. Bio-engineering testing of regenerated AS with
      cultivation of leaf cabbage Brassica chinensis L. attested to suitability of the
      technology for extension of AS useful life.

PMID- 23116045
TI  - [Changes in rats' pain sensitivity reaction after 21-day suspension].
AB  - In an experiment with 21-d suspension rats were found to increase reliably the
      threshold of pain sensitivity to thermal stress. It was hypothesized that the
      major mechanism of these changes is stress-induced analgesia as a result of
      increased hormonal secretion by the end member of the hypothalamo-pituitary
      adrenal axis.

PMID- 23116046
TI  - [Compositon of disdtribution of mineral elements in rats' bone samples after 14
      day suspension and ensuing exposure in a low-frequency pulsed magnetic field].
AB  - In experiments with 14-d suspension of rats as a model of weight load removal
      laser spark emission spectroscopy showed that minerals (Ca, P, Zn) tended upward
      in cranial bones and downward in tibia, more significantly in the epiphysis than
      in the shaft. Exposure in a low-frequency pulsed magnetic field after suspension
      had an inhibitory effect on regain of initial mineral status in bones.

PMID- 23116047
TI  - [Notion of A.L. Chizhevsky of rhythm and present-day foundations of space
      biorhythmology].
AB  - Space biorhythmology is a space medicine discipline that came into being at the
      very beginning of Russian piloted cosmonautics for the purposes of scientific
      substantiation of the principles of managing human work and rest cycle during
      space flight. The article states the link between space biorhythmology and the
      Chizhevsky fundamental ideas of periodicity as a feature of the universe key to
      stability of natural phenomena in time and space. The authors discuss main
      results of experimental and theoretical researches in the field of space
      biorhythmology in the ground laboratory and spaceflight conditions.

PMID- 23116048
TI  - [Modern information technologies and quality control of medical certification of
      extreme occupations employees].

PMID- 23116049
TI  - [Key focuses of research and practical issues of aerospace, marine and
      environmental medicine: 83rd annual meeting of the Aerospace Medical Association
      (ASM)].

PMID- 23116050
TI  - Complex cation order in anion-deficient Ba(n)YFe(n-1)O(2.5n) perovskite phases.
AB  - The synthesis and structural characterization of BanYFen-1O2.5n (n = 2, 3, 4)
      anion-deficient perovskite phases is reported. The n = 2 and n = 3 members of the
      series, Ba2YFeO5 and Ba3YFe2O7.5, adopt structures which consist of ordered
      arrays of corner-linked YO6 octahedra and FeO4 tetrahedra on the perovskite B
      sites and are described in unit cells related to a simple cubic perovskite cell
      by respective 2?2 * ?2 * 2 and 3?2 * ?2 * 2 geometric expansions. The complex
      cation ordering schemes observed in the two phases can be described on the basis
      of Y2Fe2O10?2 secondary building units. A rationalization for the observed
      structures is presented on the basis of the need to minimize lattice strain while
      maintaining the integrity of the local YO6 and FeO4 coordination polyhedra. The n
      = 4 member of the series, Ba4YFe3O10, adopts a cation and anion-vacancy
      disordered structure, which is attributed to dilution of the structure directing
      effects at extreme Y:Fe stoichiometric ratios. Magnetization data indicate
      Ba2YFeO5 and Ba3YFe2O7.5 exhibit paramagnetic behavior, consistent with the lack
      of a long-range Fe-O-Fe network. Ba4YFe3O10 adopts an antiferromagnetic state
      below 50 K. 

PMID- 23116051
TI  - Smoking cessation interventions with female smokers living with HIV/AIDS: a
      randomized pilot study of motivational interviewing.
AB  - Smoking among people living with HIV, particularly women living with HIV, is
      associated with higher morbidity and mortality rates when compared to nonsmoking
      individuals with HIV. Despite patients' higher risk of adverse health outcomes,
      in particular preventable smoking-related diseases for smokers living with HIV,
      few smoking cessation interventions have been examined with this population. The
      aim of the current study was to test the potential efficacy of a brief
      motivational intervention for smoking cessation with HIV-infected women smokers.
      Participants (N=30) were randomly assigned to receive a single session of
      motivational interviewing (MI) or prescribed advice (PA). The primary outcome was
      seven-day point prevalence abstinence at the one-month follow-up interview.
      Secondary outcome measures included mean cigarettes smoked per day, desire to
      quit smoking, perceived difficulty in quitting smoking, and expectation of
      success. We detected no significant differences between intervention and control
      groups in self-reported seven-day point prevalence abstinence at the one-month
      follow-up. However, participants in the MI condition reported a significant
      decrease in the mean cigarettes smoked per day when compared to the PA condition.
      There were no significant between-group differences in participants' desire to
      quit, perceived difficulty, and expectation of success. The results of this pilot
      study indicate that MI may be an effective smoking cessation intervention for HIV
      positive women smokers and should be studied further in a larger clinical trial.

PMID- 23116052
TI  - Angular dependence of surfactant-mediated forces between carbon nanotubes.
AB  - We employ dissipative particle dynamics to examine surfactant-mediated forces
      between two carbon nanotubes. Calculations are performed varying both the
      distance and the angle between the nanotubes. For small distances, a repulsive
      region is observed, followed by an overall attractive interval with strong
      oscillations in the force. Decreasing the angle between the tubes leads to a
      steady increase in the force, but the relative dependence on the separation
      distance is preserved. We find that the force scales linearly with the size of
      the overlap area between the tubes. This allows us to express the angle
      dependence by a simple equation, whereas the distance dependence is represented
      by a master curve. For the parallel case, the behavior is significantly
      different.

PMID- 23116053
TI  - Functionalization of microstructured open-porous bioceramic scaffolds with human
      fetal bone cells.
AB  - Bone substitute materials allowing trans-scaffold migration and in-scaffold
      survival of human bone-derived cells are mandatory for development of cell
      engineered permanent implants to repair bone defects. In this study, we evaluated
      the influence on human bone-derived cells of the material composition and
      microstructure of foam scaffolds of calcium aluminate. The scaffolds were
      prepared using a direct foaming method allowing wide-range tailoring of the
      microstructure for pore size and pore openings. Human fetal osteoblasts (osteo
      progenitors) attached to the scaffolds, migrated across the entire bioceramic
      depending on the scaffold pore size, colonized, and survived in the porous
      material for at least 6 weeks. The long-term biocompatibility of the scaffold
      material for human bone-derived cells was evidenced by in-scaffold determination
      of cell metabolic activity using a modified MTT assay, a repeated WST-1 assay,
      and scanning electron microscopy. Finally, we demonstrated that the osteo
      progenitors can be covalently bound to the scaffolds using biocompatible click
      chemistry, thus enhancing the rapid adhesion of the cells to the scaffolds.
      Therefore, the different microstructures of the foams influenced the migratory
      potential of the cells, but not cell viability. Scaffolds allow covalent
      biocompatible chemical binding of the cells to the materials, either localized or
      widespread integration of the scaffolds for cell-engineered implants.

PMID- 23116054
TI  - RAFT polymerization of bio-based 1-vinyl-4-dianhydrohexitol-1,2,3-triazole
      stereoisomers obtained via click chemistry.
AB  - Four 1-vinyl-4-dianhydrohexitol-1,2,3-triazole stereoisomers are prepared from
      isomannide, isoidide, and isosorbide using an alkylation/CuAAC
      ligation/elimination three-step strategy. After characterization of the monomers
      by NMR, differential scanning calorimetry (DSC), and high-resolution mass
      spectrometry (HRMS), the corresponding stereocontrolled poly(1-vinyl-4
      dianhydrohexitol-1,2,3-triazole)s are obtained by RAFT polymerization using a
      xanthate chain transfer agent. A systematic investigation of the structure
      properties relationship of both the monomers and polymers highlights the
      significant impact of the dianhydrohexitols stereochemistry on their physical
      properties (1H and 13C NMR chemical shifts, physical state, Tg, thermal stability
      and solubility). A particularly original and unexpected behavior is highlighted
      since the two different isosorbide-based poly(1-vinyl-4-dianhydrohexitol-1,2,3
      triazole) stereoisomers exhibit contrasting solubility in water.

PMID- 23116055
TI  - Management of retained intervention guide-wire: a literature review.
AB  - Percutaneous coronary angioplasty is increasingly employed in the treatment of
      patients with complex coronary artery disease. Different steerable guide wires
      used to open occluded vessel and facilitate balloon and stent deployment.
      However, the guide-wire itself is not without hazard: it may perforate or dissect
      the vessel, but fracture or entrapment is uncommon. Its management depends on the
      clinical situation of the patient, as well as the position and length of the
      remnant. In this review we discuss the angioplasty guide-wire fracture and
      entrapment risk factors, potential risks and management.

PMID- 23116056
TI  - Standardization of QRS duration measurement and LBBB criteria in CRT trials and
      clinical practice.
AB  - Based on the clinical trials so far, there is a major controversy regarding the
      benefit of CRT in patients with QRS<=150 milliseconds. Some studies have shown
      that a fair number of patients with QRS<=150 milliseconds benefit from CRT and it
      is needless to say that careful attention should be paid to CRT non-responders
      considering the risk of complications and cost-benefit ratio. Lack of uniformity
      in QRS measurement in all these trials could have a major influence on variable
      study outcomes. This is of concern because when the QRS is close to 120
      milliseconds in patients with NYHA class III/IV symptoms or QRS close to 150
      milliseconds in NYHA class I/II patients, the decision to recommend CRT
      implantation or undertake further risk stratification investigations is
      critically dependent on the EKG interpretation. In this paper we intent to raise
      the important question for need of standardized electrocardiographic criteria
      (QRS measurement and LBBB) in patients enrolled in CRT trials considering the
      variability in study results, high rates of CRT non response in the eligible
      population and the associated health care cost burden.

PMID- 23116058
TI  - The BCL2L11 (BIM) deletion polymorphism is a possible criterion for
      discontinuation of imatinib in chronic myeloid leukaemia patients.

PMID- 23116059
TI  - Synergic study of alpha-glucosidase inhibitory action of aloin and its
      antioxidant activity with and without camel beta-casein and its peptides.
AB  - Regular consumption of natural antioxidants reduces the risk of developing
      diseases. Aloin is one of the main active phenolic components of Aloe vera. The
      main disadvantage of aloin is its concentration limit of use that causes cell
      damage. One of the aims of this study was to investigate the antioxidant activity
      of aloin in the presence and absence of camel beta-casein ( beta-CN) and its
      peptide fractions. The mixture of aloin, beta-CN and peptides showed a very high
      antioxidant activity in a synergistic manner as compared to each component alone.
      The alpha ( alpha)-glucosidase inhibitory activity of aloin was also investigated
      in the presence and absence of beta-CN and its peptides. Aloin alone is a potent
      inhibitor of alpha-glucosidase. The alpha-glucosidase inhibitory activity of
      aloin is reduced in the presence of beta-CN or its peptides. The combination of
      aloin and beta-CN or its peptides makes a high antioxidant functional ingredient.

PMID- 23116060
TI  - Seroprevalence of Toxoplasma gondii infection in fattening pigs in Northeast
      China.
AB  - Seroprevalence of Toxoplasma gondii infection in fattening pigs in Heilongjiang
      Province, northeast China, was investigated between July 2011 and June 2012. In
      total, 1,014 pig serum samples were collected from 10 administrative regions and
      assayed for T. gondii antibodies by indirect hemagglutination (IHA) test using a
      commercially available kit. The average T. gondii antibody-positive prevalence
      was 4.6% (47/1,014), which is relatively lower than that in other provinces in
      China. Seroprevalence in fattening pigs raised on small farms (6.3%) was
      significantly higher than that on large farms (3.8%) (P < 0.05), and the
      seroprevalence ranged from 2.4% (Shuangyashan) to 6.8% (Qitaihe) between
      different geographical regions. Given that pork is not examined for T. gondii
      infection in China by law, these findings have public health implications and
      provide useful baseline information for the control of pig toxoplasmosis in this
      unique region of China.

PMID- 23116057
TI  - Regulation of the cardiac sodium/bicarbonate cotransporter by angiotensin II:
      potential Contribution to structural, ionic and electrophysiological myocardial
      remodelling.
AB  - The sodium/ bicarbonate cotransporter (NBC) is, with the Na+/H+ exchanger (NHE),
      an important alkalinizing mechanism that maintains cellular intracellular pH
      (pHi). In the heart exists at least three isoforms of NBC, one that promotes the
      co-influx of 1 molecule of Na+ per 1molecule of HCO3-(electroneutral isoform;
      nNBC) and two others that generates the co-influx of 1 molecule of Na+ per 2
      molecules of HCO3- (electrogenic isoforms; eNBC). In addition, the eNBC generates
      an anionic repolarizing current that modulate the cardiac action potential (CAP),
      adding to such isoforms the relevance to modulate the electrophysiological
      function of the heart. Angiotensin II (Ang II) is one of the main hormones that
      regulate cardiac physiology. The alkalinizing mechanisms (NHE and NBC) are
      stimulated by Ang II, increasing pHi and intracellular Na+ concentration, which
      indirectly, due to the stimulation of the Na+/Ca2+ exchanger (NCX) operating in
      the reverse form, leads to an increase in the intracellular Ca2+ concentration.
      Interestingly, it has been shown that Ang II exhibits an opposite effect on NBC
      isoforms: it activates the nNBC and inhibits the eNBC. This inhibition generates
      a CAP prolongation, which could directly increase the intracellular Ca2+
      concentration. The regulation of the intracellular Na+ and Ca2+ concentrations is
      crucial for the cardiac cellular physiology, but these ions are also involved in
      the development of cardiac hypertrophy and the damage produced by ischemia
      reperfusion, suggesting a potential role of NBC in cardiac diseases.

PMID- 23116061
TI  - Trends in gestational age and birth weight in Chile, 1991-2008. A descriptive
      epidemiological study.
AB  - BACKGROUND: Gestational age and birth weight are the principal determinants of
      newborn's health status. Chile, a middle income country traditionally has public
      policies that promote maternal and child health. The availability of an
      exhaustive database of live births has allows us to monitor over time indicators
      of newborns health. METHODS: This descriptive epidemiological study included all
      live births in Chile, both singleton and multiple, from 1991 through 2008. Trends
      in gestational age affected the rate of prevalence (%) of preterm births (<37
      weeks, including the categories < 32 and 32-36 weeks), term births (37-41) and
      postterm births (42 weeks or more). Trends in birth weight affected the
      prevalence of births < 1500 g, 1500-2499 g, 2500-3999 g, and 4000 g or more.
      RESULTS: Data from an exhaustive register of live births showed that the number
      of term and postterm births decreased and the number of multiple births increased
      significantly. Birth weights exceeding 4000 g did not vary.Total preterm births
      rose from 5.0% to 6.6%, with increases of 28% for the singletons and 31% for
      multiple births (p for trend < 0.0001). Some categories increased even more:
      specifically preterm birth < 32 weeks increased 32.3% for singletons and 50.6%
      for multiple births (p for trend 0.0001).The overall rate of low birth weight
      infants (<2500 g) increased from 4.6% to 5.3%. This variation was not
      statistically significant for singletons (p for trend = 0.06), but specific
      analyses exhibited an important increase in the category weighing <1500 g (42%)
      similar to that observed in multiple births (43%). CONCLUSIONS: The gestational
      age and birth weight of live born child have significantly changed over the past
      two decades in Chile. Monitoring only overall rates of preterm births and low
      birth-weight could provide restricted information of this important problem to
      public health. Monitoring them by specific categories provides a solid basis for
      planning interventions to reduce adverse perinatal outcomes.This epidemiological
      information also showed the need to assess several factors that could contribute
      to explain these trends, as the demographics changes, medical interventions and
      the increasing probability of survival of extremely and very preterm child.

PMID- 23116062
TI  - The cost of unresectable stage III or stage IV melanoma in Italy.
AB  - BACKGROUND: In recent decades, melanoma incidence has been increasing in European
      countries; in 2006, there were approximately 60,000 cases leading to 13,000
      deaths. Within Europe there is some geographical variation in the incidence of
      melanoma, with the highest rates reported in Scandinavia (15 cases per 100,000
      inhabitants per year) and the lowest in the Mediterranean countries (5 to 7 cases
      per 100,000 inhabitants per year). METHODS: The present article is based on the
      information collected in the MELODY study (MELanoma treatment patterns and
      Outcomes among patients with unresectable stage III or stage IV Disease: a
      retrospective longitudinal survey).In that study, the medical charts of patients
      were reviewed to document current treatment patterns and to analyse information
      on patients, disease characteristics and healthcare resource utilization related
      to the treatment of advanced melanoma regarding patients who presented with a
      diagnosis of malignant melanoma (stage I to IV) at participating sites between 01
      July, 2005 and 30 June, 2006. RESULTS: Summarizing, though the length of the
      follow-up period varies among sample patients, an amount of the yearly cost per
      patient can be estimated, dividing the average per patient total cost (? 5.040)
      by the average follow-up duration (17.5 months) and reporting to one year; on
      these grounds, unresectable stage III or stage IV melanoma in Italy would cost ?
      3,456 per patient per year.

PMID- 23116064
TI  - Electrocyclization of oxatrienes in the construction of structurally complex
      pyranopyridones.
AB  - Application of a tandem Knoevenagel/6pi-electrocyclization sequence is able to
      produce highly substituted pyranopyridones from moderate to high yields in a one
      step reaction. High diasteroselectivity is observed in some cases and was
      rationalized on the basis of the thermodynamic control of the evidenced
      reversibility of a 6pi-electrocyclization reaction. Numerous examples are
      provided establishing a novel entry in natural product-like structures of
      pyranopyridone alkaloids.

PMID- 23116063
TI  - Heat shock factor-1 intertwines insulin/IGF-1, TGF-beta and cGMP signaling to
      control development and aging.
AB  - BACKGROUND: Temperature affects virtually all cellular processes. A quick
      increase in temperature challenges the cells to undergo a heat shock response to
      maintain cellular homeostasis. Heat shock factor-1 (HSF-1) functions as a major
      player in this response as it activates the transcription of genes coding for
      molecular chaperones (also called heat shock proteins) that maintain structural
      integrity of proteins. However, the mechanisms by which HSF-1 adjusts fundamental
      cellular processes such as growth, proliferation, differentiation and aging to
      the ambient temperature remain largely unknown. RESULTS: We demonstrate here that
      in Caenorhabditis elegans HSF-1 represses the expression of daf-7 encoding a TGF
      beta (transforming growth factor-beta) ligand, to induce young larvae to enter
      the dauer stage, a developmentally arrested, non-feeding, highly stress
      resistant, long-lived larval form triggered by crowding and starvation. Under
      favorable conditions, HSF-1 is inhibited by crowding pheromone-sensitive
      guanylate cyclase/cGMP (cyclic guanosine monophosphate) and systemic nutrient
      sensing insulin/IGF-1 (insulin-like growth factor-1) signaling; loss of HSF-1
      activity allows DAF-7 to promote reproductive growth. Thus, HSF-1 interconnects
      the insulin/IGF-1, TGF-beta and cGMP neuroendocrine systems to control
      development and longevity in response to diverse environmental stimuli.
      Furthermore, HSF-1 upregulates another TGF-beta pathway-interacting gene, daf
      9/cytochrome P450, thereby fine-tuning the decision between normal growth and
      dauer formation. CONCLUSION: Together, these results provide mechanistic insight
      into how temperature, nutrient availability and population density coordinately
      influence development, lifespan, behavior and stress response through HSF-1.

PMID- 23116065
TI  - Practical recommendations for patient blood management and the reduction of
      perioperative transfusion in joint replacement surgery.
AB  - Data from the Australian Better Safer Transfusion programme show that about one
      third of patients undergoing hip or knee arthroplasty receive perioperative blood
      transfusions, placing them at increased risk for adverse clinical outcomes. Other
      concerns associated with allogeneic blood transfusion include the quality of
      stored red cell concentrates, the cost of provision of blood and the predicted
      local demographics, which mean that fewer donors will need to support a greater
      number of recipients. In view of the multiple challenges associated with
      allogeneic blood transfusion and its provision, we developed practical management
      recommendations for perioperative bleeding in joint replacement surgery, based on
      available evidence and expert consensus opinion, that aim to promote a new,
      responsible approach to transfusion management. Key recommendations are as
      follows. Patients' medical health, including haemoglobin and iron levels, needs
      to be evaluated and optimized preoperatively. Anticoagulant and antiplatelet
      therapy should be stopped if possible, unless indicated for secondary
      cardiovascular prevention or coronary stent patency, in which case careful
      consideration is required. If substantial blood loss is anticipated,
      intraoperative management with antifibrinolytic agents is recommended for
      bleeding prophylaxis. Normothermia should be maintained. Pharmacological and non
      pharmacological measures are recommended for post-operative thromboprophylaxis. A
      blood management programme should be instituted for haemodynamically stable
      patients.

PMID- 23116066
TI  - The DEAD/DEAH box helicase, DDX11, is essential for the survival of advanced
      melanomas.
AB  - BACKGROUND: Despite continuous efforts to identify genes that are pivotal
      regulators of advanced melanoma and closely related to it, to determine which of
      these genes have to be blocked in their function to keep this highly aggressive
      disease in check, it is far from clear which molecular pathway(s) and specific
      genes therein, is the Achilles' heel of primary and metastatic melanoma. In this
      report, we present data, which document that the DEAD-box helicase DDX11, which
      is required for sister chromatid cohesion, is a crucial gatekeeper for melanoma
      cell survival. METHODS: Performing immunohistochemistry and immunoblot analysis,
      we determined expression of DDX11 in melanoma tissues and cell lines. Following
      transfection of melanoma cells with a DDX11-specific siRNA, we conducted a qPCR
      analysis to determine downregulation of DDX11 in the transfected melanoma cells.
      In subsequent studies, which focused upon an analysis of fluorescently labeled as
      well as Giesma-stained chromosome spreads, a proliferation analysis and apoptosis
      assays, we determined the impact of suppressing DDX11 expression on melanoma
      cells representing advanced melanoma. RESULT: The findings of the study presented
      herein document that DDX11 is upregulated with progression from noninvasive to
      invasive melanoma, and that it is expressed at high levels in advanced melanoma.
      Furthermore, and equally important, we demonstrate that blocking the expression
      of DDX11 leads not only to inhibition of melanoma cell proliferation and severe
      defects in chromosome segregation, but also drives melanoma cells rapidly into
      massive apoptosis. CONCLUSION: To date, little is known as to whether helicases
      play a role in melanoma development and specifically, in the progression from
      early to advanced melanoma. In this report, we show that the helicase DDX11 is
      expressed at high levels in primary and metastatic melanoma, and that interfering
      with its expression leads to severe chromosome segregation defects, telomere
      shortening, and massive melanoma cell apoptosis. These findings suggest that
      DDX11 could be an important candidate for molecular targeted therapy for advanced
      melanoma.

PMID- 23116067
TI  - Tranexamic acid solution soaking is an excellent approach for rosacea patients: a
      preliminary observation in six patients.

PMID- 23116068
TI  - Giving failed drugs a fresh chance: a new direction for nanoparticle drug
      delivery.

PMID- 23116069
TI  - How serious an adverse event is longitudinal stent deformation? Incidence and
      severity.

PMID- 23116070
TI  - In situ heart valve tissue engineering: simple devices, smart materials, complex
      knowledge.

PMID- 23116071
TI  - Scaffolds for vascularized bone regeneration: advances and challenges.

PMID- 23116073
TI  - The CyberKnife radiosurgery system for lung cancer.
AB  - The CyberKnife is a frameless image-guided radiotherapy system involving a 6-MV
      linear accelerator mounted on a robotic arm. The imaging system consists of two
      diagnostic x-ray sources mounted to the ceiling paired with amorphous silicon
      detectors to acquire live digital radiographic images of the tumor or tumor
      surrogates including bony anatomy or implanted fiducial markers. The Synchrony
      system enables 4D real-time tracking of tumors that move with respiration. Owing
      to this complex system, moving tumors can be treated with an accuracy of 2 mm or
      less while patients breathe normally. Clinical results of inoperable patients
      with peripheral early-stage lung cancer are excellent. The toxicity is low and
      the treatment does not result in a loss in quality of life.

PMID- 23116074
TI  - Sacral nerve stimulation for fecal incontinence.
AB  - Fecal incontinence (FI), which can severely affect a person's quality of life, is
      a difficult problem to treat. For some patients, limited management options
      exist. Sacral nerve stimulation, also known as sacral neuromodulation, although
      long established for urinary incontinence, has gained acceptance in treating FI.
      One unique aspect is that the procedure is performed in two stages. During the
      first stage, a temporary lead is inserted into the S3 sacral foramen and the
      patient can monitor improvement before a permanent device is implanted. While
      this procedure has proven to be effective for treating FI, it is also attractive
      owing to the low morbidity and low infection risk reported in the literature.

PMID- 23116075
TI  - The magnetic anal sphincter: a new device in the management of severe fecal
      incontinence.
AB  - The authors aim to report the concept and technique of implantation and the first
      results of the clinical use of the magnetic anal sphincter (MAS) in the
      management of fecal incontinence (FI). The MAS device is designed to augment the
      native anal sphincter. The implant is a series of titanium beads with magnetic
      cores linked together with independent titanium wires. To defecate, the force
      generated by straining separates the beads to open up the anal canal. The
      technique of implantation is simple with no requirement of adjustments. The MAS
      has a role in the management of severe FI. The device has acceptable and
      comparable adverse effects to other therapies. FI and Fecal Incontinence Quality
      of Life scores are significantly improved in the short term. The MAS offers a
      simple and less invasive option of anal reinforcement. It is one step further in
      the quest for an ideal artificial anal sphincter device.

PMID- 23116077
TI  - Neonatal hemodynamics: monitoring, data acquisition and analysis.
AB  - Monitoring of cardiovascular function is critical to both clinical care and
      research as the use of sophisticated monitoring systems enable us to obtain
      accurate, reliable and real-time information on developmental hemodynamics in
      health and disease. Novel approaches to comprehensive hemodynamic monitoring and
      data acquisition will undoubtedly aid in developing a better understanding of
      developmental cardiovascular physiology in neonates. In addition, development and
      use of state-of-the-art, comprehensive hemodynamic monitoring systems enable the
      recognition of signs of cardiovascular compromise in its early stages, and
      provide information on the hemodynamic response to treatment in critically ill
      patients.

PMID- 23116078
TI  - A review of thrombectomy devices.
AB  - Acute coronary syndrome is associated with a high incidence of thrombus. The
      presence of coronary thrombus is often not appreciated on coronary angiography;
      however, simultaneous use of angioscopy or intravascular ultrasound increases the
      detection of thrombus. Forceful coronary injection, passage of intracoronary
      devices, balloon angioplasty and stenting in the presence of thrombus contribute
      to distal embolization by disrupting the thrombus. Clinically, intracoronary
      thrombus is associated with higher rates of death, myocardial infarction and
      target vessel revascularization. Removal of thrombus results in the improvement
      of markers of perfusion, which includes resolution of ST segment elevation,
      higher myocardial blush grade, and an increase in final thrombolysis in
      myocardial infarction flow as well as lower mortality. In this article, the
      authors discuss different mechanical thrombectomy devices and the literature
      available for their use in acute coronary syndrome.

PMID- 23116076
TI  - Neuronavigation in the surgical management of brain tumors: current and future
      trends.
AB  - Neuronavigation has become an ubiquitous tool in the surgical management of brain
      tumors. This review describes the use and limitations of current
      neuronavigational systems for brain tumor biopsy and resection. Methods for
      integrating intraoperative imaging into neuronavigational datasets developed to
      address the diminishing accuracy of positional information that occurs over the
      course of brain tumor resection are discussed. In addition, the process of
      integration of functional MRI and tractography into navigational models is
      reviewed. Finally, emerging concepts and future challenges relating to the
      development and implementation of experimental imaging technologies in the
      navigational environment are explored.

PMID- 23116079
TI  - Optimizing benefit from CRT: role of speckle tracking echocardiography, the
      importance of LV lead position and scar.
AB  - Cardiac resynchronization therapy is demonstrated to be effective in patients
      with advanced heart failure. Correcting mechanical dyssynchrony is proposed as
      the predominant mechanism of response. Achieving optimum left ventricular lead
      position, at the site of maximal mechanical dyssynchrony but away from transmural
      scar, is identified as one of the main determinants of both symptomatic and
      prognostic benefit. Strategies employing multimodality cardiac imaging techniques
      have been used to identify this optimal pacing site, in addition to any potential
      anatomical limitations to successful implantation. Speckle tracking
      echocardiography offers prospective lead targeting, incorporating
      pathophysiological determinants of cardiac resynchronization therapy response.
      This review considers the key factors in defining optimum left ventricular lead
      location, emphasizing the role of myocardial scar. The use of speckle tracking
      echocardiography and the potential for this technique to be incorporated into
      routine practice to guide the implant strategy in an individual patient is
      discussed.

PMID- 23116080
TI  - Modeling of the medical device development process.
AB  - Models are abstract representations of reality that are built, analyzed and
      manipulated to augment the understanding of that reality. They can either be
      mental or codified but, in both cases, they contribute to good decision-making by
      ensuring that the right people use the right information at the right time. In
      order to reduce time to market, companies commonly adopt product development
      processes (PDP) and the medical device sector is no different. However, one can
      question which is the most adequate PDP model to follow or what information that
      model should contain, or even how the information should be represented. Here,
      the authors review the existing PDP models dedicated to medical devices. The
      model's representation and usability are also debated in order to assist
      developers to select the most suitable model and adapt it to their needs and
      reality.

PMID- 23116082
TI  - Cultural differences in sensitivity to social context: detecting affective
      incongruity using the N400.
AB  - East Asians and Asian-Americans tend to allocate relatively greater attention to
      background context compared to European Americans across a variety of cognitive
      and neural measures. We sought to extend these findings of cultural differences
      to affective stimuli using the N400, which has been shown to be sensitive to deep
      processing of affective information. The degree to which Asian-Americans and
      European Americans responded to semantic incongruity between emotionally
      expressive faces (i.e., smiling or frowning) and background affective scenes was
      measured. As predicted, Asian-Americans showed a greater N400 to incongruent
      trials than to congruent trials. In contrast, European Americans showed no
      difference in amplitude across the two conditions. Furthermore, greater affective
      N400 incongruity was associated with higher interdependent self-construals. These
      data suggest that Asian-Americans and those with interdependent self-construals
      process the relationship between perceived facial emotion and affective
      background context to a greater degree than European Americans and those with
      independent self-construals. Implications for neural and cognitive differences in
      everyday social interactions, and cultural differences in analytic and holistic
      thinking are discussed.

PMID- 23116084
TI  - Systemic and biophase bioavailability and pharmacokinetics of nanoparticulate
      drug delivery systems.
AB  - The development of the vectorized delivery systems combining advantages of the
      colloidal carriers, with active targeting to the receptors sites suggests that
      nanoparticles have a considerable potential for treatment after biophase
      internalization and pharmacokinetics, as for example gene therapy. Two major
      mechanisms can be distinguished for addressing the desired sites for drug
      release: (i) passive and (ii) active targeting. Examples of passive targeting
      were presented: organ targeting by the Enhanced Permeability and Retention (EPR)
      effect; targeting the mononuclear phagocitic system; organ targeting by
      chemoembolization or local (organ) administration;sterical stabilization of
      nanoparticles (PEGylation). A strategy that could allow active targeting involves
      the surface functionalization of drug carriers with ligands that are selectively
      recognized by receptors on the surface of the cells of interest. The source for
      biophase bioavailability can be the systemic bioavailability following common
      routes of administration (generally for systemic delivery of medicines), or
      directly the site specific biophase bioavailability for the formulations capable
      of cellular or nuclear drug internalization where the drug release only will take
      place (for nanoparticulate drug delivery systems, DDS). Once the pharmaceutical
      nanosystem was internalized, begins the release of the active moiety by different
      mechanisms, as for example the escape from endosome, or biodegradation of the
      polymer carrier or liberation of the active peptide or gene from a biological
      construct in the nucleus, etc. The presentation will discusses the
      pharmacokinetics of drugs after systemic administration but especially the
      biophase bioavailability and pharmacokinetics after the administration of
      biotechnology origin of therapeutic proteins like monoclonal antibodies, gene
      transfer products, plasmid DNAs, nucleotides, antisense oligonucleotides (AODNs)
      or small interfering RNAs (siRNA).

PMID- 23116083
TI  - Persistent current blockers of voltage-gated sodium channels: a clinical
      opportunity for controlling metastatic disease.
AB  - A range of experimental and clinical data suggests strongly (i) that metastatic
      progression in carcinomas is accompanied (maybe even preceded) by upregulation of
      functional voltage-gated sodium channels (VGSCs) and (ii) that VGSC activity
      enhances cancer cell invasiveness. First, this review outlines the available in
      vitro and in vivo evidence for the VGSC expression and its proposed
      pathophysiological role. Second, we question the mechanism(s) whereby VGSC
      activity can induce such a cancer-promoting effect. We advance the hypothesis
      that it is the hypoxia-sensitive persistent component of the VGSC current (INaP)
      that is central to the phenomenon. Indeed, blockers of INaP are very effective in
      suppressing cancer cell invasiveness in vitro. Based upon these data, UK and
      international patent applications have been filed which describe the use of INaP
      blockers, like ranolazine ("Ranexa") and riluzole ("Rilutex"), as anti-metastatic
      agents. Importantly, since these drugs are already in clinical use, against
      conditions like cardiac angina and amyotrophic lateral scelerosis, there are no
      issues of dosage, unacceptable side effects or long-term use. Thus, INaP blockers
      have the potential to turn cancer into a chronic condition.

PMID- 23116085
TI  - Real-time simulation of large-scale neural architectures for visual features
      computation based on GPU.
AB  - The intrinsic parallelism of visual neural architectures based on distributed
      hierarchical layers is well suited to be implemented on the multi-core
      architectures of modern graphics cards. The design strategies that allow us to
      optimally take advantage of such parallelism, in order to efficiently map on GPU
      the hierarchy of layers and the canonical neural computations, are proposed.
      Specifically, the advantages of a cortical map-like representation of the data
      are exploited. Moreover, a GPU implementation of a novel neural architecture for
      the computation of binocular disparity from stereo image pairs, based on
      populations of binocular energy neurons, is presented. The implemented neural
      model achieves good performances in terms of reliability of the disparity
      estimates and a near real-time execution speed, thus demonstrating the
      effectiveness of the devised design strategies. The proposed approach is valid in
      general, since the neural building blocks we implemented are a common basis for
      the modeling of visual neural functionalities.

PMID- 23116086
TI  - Seroprevalence of Toxoplasma gondii infection in dairy goats in Michoacan State,
      Mexico.
AB  - Seroprevalence of Toxoplasma gondii infection in goats in Michoacan, Mexico, is
      largely unknown. Antibodies to T. gondii were determined in 341 dairy goats in
      Michoacan, Mexico, using the modified agglutination test. Goats were raised in 9
      farms in 6 municipalities. Overall, antibodies to Toxoplasma were found in 52
      (15.2%) of 341 goats, with titers of 1:25 in 16, 1:50 in 9, 1:100 in 4, 1:200 in
      4, 1:400 in 4, 1:800 in 9, 1:1,600 in 3, and 1:3,200 or higher in 3. Seropositive
      goats were found in all 9 farms sampled, and seroprevalence varied significantly
      among farms (1.9-90%). Seroprevalence of T. gondii varied with age, municipality,
      altitude, and climate but not with breed. Increased seroprevalence was found in
      goats aged 13-24 and 49-86 mo old (25% and 22.9%, respectively). Goats raised in
      farms in a municipality with semi-warm humid climate at 1,700 m of altitude had
      the highest seroprevalence (62.1%). This is the first report of T. gondii
      infection in goats in Michoacan State, Mexico, and of an association of
      seropositivity to T. gondii and semi-warm humid climate. Results indicate that
      infected goats are likely an important source of infection with T. gondii in
      humans in Michoacan State.

PMID- 23116087
TI  - Accreditation of birth centres: advantages for newborns.
AB  - Accreditation or certification of Health Care Providers is a crucial tool to
      improve health care quality, and to promote excellence. Excellent healthcare
      should have the following six characteristics: Safe, Effective, Person-centred,
      Timely, Efficient, Equitable. Safety in health care should consider the analysis
      and reduction of medical systematic errors and their related patients' harm. In
      1999 the U.S. Institute of Medicine defined medical errors as the failure of a
      planned action to be completed as intended or the use of a wrong plan to achieve
      an aim. In neonatal intensive care units and pediatric intensive care units the
      areas most frequently associated with medical errors are medication, including
      prescribing, preparation, administration and monitoring; health-care associated
      infections; mechanical ventilation; events related to the use of medical devices
      or procedures and, more recently, caregivers fatigue and communication
      strategies. In Italy, Maternal-Neonatal Health is one of the national priorities,
      but there are still wide and deep differences among Regions. In 2008, more than
      9% of the deliveries occurred in Hospitals with less than 500 births per year, a
      volume considered too small to guarantee optimal standard of care. In 2010, the
      National Government and the Regional Health Authorities agreed to set to 1000
      births/year the standard threshold for Hospital Birth Centers, considering the
      same volume for obstetric-gynecologic and neonatal-pediatrics Units. Despite most
      indicators attest the good performance of the National health care, a further
      area to be addressed is the perception of its quality by the people. The
      discrepancy between quality of care and its public perception is in fact reported
      in many industrialized countries. Accreditation programs can improve the
      availability and access to a standardized quality of care. A well-established
      worldwide accreditation program is led by Joint Commission International (JCI).
      As far as accreditation of perinatal care is regarded, in 2010 the U.S. Joint
      Commission has defined a set of measures known as the perinatal care core measure
      set, which consider elective delivery, cesarean section, antenatal steroids,
      healthcare-associated bloodstream infections in newborns, exclusive breastmilk
      feeding. In Italy, the 2011-2013 National Health Care Plan underline the need for
      developing and implementing certification programs for Hospital Birth Centers. In
      2011, a multidisciplinary working group (Italian Group for Safe Birth) has thus
      been established. CONCLUSION: the main goal of each Health Care Organization
      should be to achieve the best quality and safety. Health Care Organizations must
      reduce random variations and improve activities by a standardized process whose
      results can be measured both in terms of patients outcome and in terms of
      transparency of each activity. Newborn and infants are one of the weakest
      population group; to improve their health outcome is thus mandatory to do all
      efforts to obtain a safe, effective, efficient and patient-centered health care
      assistance.

PMID- 23116088
TI  - Staff-focused interventions to increase referrals for depression in aged care
      facilities: a cluster randomized controlled trial.
AB  - OBJECTIVE: While there is evidence that depression training can improve the
      knowledge of staff in residential care facilities, there is an absence of
      research determining whether such training translates into practice change. This
      study aimed to evaluate the impact of staff training and the introduction of a
      protocol for routine screening and referral for depression on the numbers of
      residents detected and referred by care staff for further assessment. METHOD: A
      cluster randomized controlled design was used to compare the referral rates for
      residents in seven facilities randomly allocated into one of three conditions:
      staff training, staff training plus a screening and referral protocol and wait
      list control. Participants were 216 aged care residents (M age = 87 years), who
      agreed to a 12-month audit of their facility file. RESULTS: Staff training on its
      own did not increase the rate of referrals for depression; however, staff
      training plus the screening protocol and referral guidelines did lead to a
      significant increase in the number of residents who were referred to a medical
      practitioner for further assessment. However, this increase in care staff
      referrals did not result in substantial changes in the treatment prescribed for
      residents. CONCLUSION: Staff training in depression, supplemented with a protocol
      for routine screening and guidelines on referring residents, can improve pathways
      to care. However, strategies to overcome barriers to appropriate subsequent
      treatment of depression are required for staff-focused initiatives to translate
      into better outcomes for depressed older adults. Methodological limitations of
      this study are discussed.

PMID- 23116089
TI  - Patterns in neurosurgical adverse events and proposed strategies for reduction.
AB  - Neurosurgery is a high-risk specialty currently undertaking the pursuit of
      systematic approaches to reducing risk and to measuring and improving outcomes.
      The authors performed a review of patterns and frequencies of adverse events in
      neurosurgery as background for future efforts directed at the improvement of
      quality and safety in neurosurgery.   They found 6 categories of contributory
      factors in neurosurgical adverse events, categorizing the events as influenced by
      issues in surgical technique, perioperative medical management, use of and
      adherence to protocols, preoperative optimization, technology, and communication.
      There was a wide distribution of reported occurrence rates for many of the
      adverse events, in part due to the absence of definitive literature in this area
      and to the lack of standardized reporting systems.   On the basis of their
      analysis, the authors identified 5 priority recommendations for improving
      outcomes for neurosurgical patients at a population level: 1) development and
      implementation of a national registry for outcome data and monitoring; 2) full
      integration of the WHO Surgical Safety Checklist into the operating room
      workflow, which improves fundamental aspects of surgical care such as adherence
      to antibiotic protocols and communication within surgical teams; and 3-5)
      activity by neurosurgical societies to drive increased standardization for the
      safety of specialized equipment used by neurosurgeons (3), more widespread
      regionalization and/or subspecialization (4), and establishment of data-driven
      guidelines and protocols (5). The fraction of adverse events that might be
      avoided if proposed strategies to improve practice and decrease variability are
      fully adopted remains to be determined. The authors hope that this consolidation
      of what is currently known and practiced in neurosurgery, the application of
      relevant advances in other fields, and attention to proposed strategies will
      serve as a basis for informed and concerted efforts to improve outcomes and
      patient safety in neurosurgery.

PMID- 23116090
TI  - Intraoperative neurophysiological monitoring in spine surgery: indications,
      efficacy, and role of the preoperative checklist.
AB  - Spine surgery carries an inherent risk of damage to critical neural structures.
      Intraoperative neurophysiological monitoring (IONM) is frequently used to improve
      the safety of spine surgery by providing real-time assessment of neural
      structures at risk. Evidence-based guidelines for safe and efficacious use of
      IONM are lacking and its use is largely driven by surgeon preference and
      medicolegal issues. Due to this lack of standardization, the preoperative sign-in
      serves as a critical opportunity for 3-way discussion between the neurosurgeon,
      anesthesiologist, and neuromonitoring team regarding the necessity for and goals
      of IONM in the ensuing case. This analysis contains a review of commonly used
      IONM modalities including somatosensory evoked potentials, motor evoked
      potentials, spontaneous or free-running electromyography, triggered
      electromyography, and combined multimodal IONM. For each modality the
      methodology, interpretation, and reported sensitivity and specificity for
      neurological injury are addressed. This is followed by a discussion of important
      IONM-related issues to include in the preoperative checklist, including
      anesthetic protocol, warning criteria for possible neurological injury, and
      consideration of what steps to take in response to a positive alarm. The authors
      conclude with a cost-effectiveness analysis of IONM, and offer recommendations
      for IONM use during various forms of spine surgery, including both complex spine
      and minimally invasive procedures, as well as lower-risk spinal operations.

PMID- 23116091
TI  - The design, development, and implementation of a checklist for intraoperative
      neuromonitoring changes.
AB  - OBJECT: The purpose of this study was to provide an evidence-based algorithm for
      the design, development, and implementation of a new checklist for the response
      to an intraoperative neuromonitoring alert during spine surgery. METHODS: The
      aviation and surgical literature was surveyed for evidence of successful
      checklist design, development, and implementation. The limitations of checklists
      and the barriers to their implementation were reviewed. Based on this review, an
      algorithm for neurosurgical checklist creation and implementation was developed.
      Using this algorithm, a multidisciplinary team surveyed the literature for the
      best practices for how to respond to an intraoperative neuromonitoring alert. All
      stakeholders then reviewed the evidence and came to consensus regarding items for
      inclusion in the checklist. RESULTS: A checklist for responding to an
      intraoperative neuromonitoring alert was devised. It highlights the specific
      roles of the anesthesiologist, surgeon, and neuromonitoring personnel and
      encourages communication between teams. It focuses on the items critical for
      identifying and correcting reversible causes of neuromonitoring alerts. Following
      initial design, the checklist draft was reviewed and amended with stakeholder
      input. The checklist was then evaluated in a small-scale trial and revised based
      on usability and feasibility. CONCLUSIONS: The authors have developed an evidence
      based algorithm for the design, development, and implementation of checklists in
      neurosurgery and have used this algorithm to devise a checklist for responding to
      intraoperative neuromonitoring alerts in spine surgery.

PMID- 23116092
TI  - Surgical briefings, checklists, and the creation of an environment of safety in
      the neurosurgical intraoperative magnetic resonance imaging suite.
AB  - Technological advances have made it possible to seamlessly integrate modern
      neuroimaging into the neurosurgical operative environment. This integration has
      introduced many new applications improving surgical treatments. One major
      addition to the neurosurgical armamentarium is intraoperative navigation and MRI,
      enabling real-time use during surgery. In the 1970s, the American College of
      Radiology issued safety guidelines for diagnostic MRI facilities. Until now,
      however, no such guidelines existed for the MRI-integrated operating room, which
      is a high-risk zone requiring standardized protocols to ensure the safety of both
      the patient and the operating room staff. The forces associated with the strong
      1.5- and 3.0-T magnets used for MRI are potent and hazardous, creating distinct
      concerns regarding safety, infection control, and image interpretation. Authors
      of this paper provide an overview of the intraoperative MRI operating room,
      safety considerations, and a series of checklists and protocols for maintaining
      safety in this zero tolerance environment.

PMID- 23116093
TI  - Patterns in neurosurgical adverse events: cerebrospinal fluid shunt surgery.
AB  - OBJECT: As part of a project to devise evidence-based safety interventions for
      specialty surgery, the authors sought to review current evidence in CSF shunt
      surgery concerning the frequency of adverse events in practice, their patterns,
      and the state of knowledge regarding methods for their reduction. This review may
      also inform future and ongoing efforts for the advancement of neurosurgical
      quality. METHODS: The authors performed a PubMed search using search terms
      "cerebral shunt," "cerebrospinal fluid shunt," "CSF shunt," "ventriculoperitoneal
      shunt," "cerebral shunt AND complications," "cerebrospinal fluid shunt AND
      complications," "CSF shunt AND complications," and "ventriculoperitoneal shunt
      AND complications." Only papers that specifically discussed the relevant
      complication rates were included. Papers were chosen to be included to maximize
      the range of rates of occurrence for the adverse events reported. RESULTS: In
      this review of the neurosurgery literature, the reported rate of mechanical
      malfunction ranged from 8% to 64%. The use of programmable valves has increased
      but remains of unproven benefit even in randomized trials. Infection was the
      second most common complication, with the rate ranging from 3% to 12% of shunt
      operations. A meta-analysis that included 17 randomized controlled trials of
      perioperative antibiotic prophylaxis demonstrated a decrease in shunt infection
      by half (OR 0.51, 95% CI 0.36-0.73). Similarly, use of detailed protocols
      including perioperative antibiotics, skin preparation, and limitation of OR
      personnel and operative time, among other steps, were shown in uncontrolled
      studies to decrease shunt infection by more than half. Other adverse events
      included intraabdominal complications, with a reported incidence of 1% to 24%,
      intracerebral hemorrhage, reported to occur in 4% of cases, and perioperative
      epilepsy, with a reported association with shunt procedures ranging from 20% to
      32%. Potential management strategies are reported but are largely without formal
      evaluation. CONCLUSIONS: Surgery for CSF shunt placement or revision is
      associated with a high complication risk due primarily to mechanical issues and
      infection. Concerted efforts aimed at large-scale monitoring of neurosurgical
      complications and consistent quality improvement within these highlighted realms
      may significantly improve patient outcomes.

PMID- 23116094
TI  - Patterns in neurosurgical adverse events: endovascular neurosurgery.
AB  - As part of a project to devise evidence-based safety interventions for specialty
      surgery, the authors sought to review current evidence in endovascular
      neurosurgery concerning the frequency of adverse events in practice, their
      patterns, and current methods of reducing the occurrence of these events. This
      review represents part of a series of papers written to consolidate information
      about these events and preventive measures as part of an ongoing effort to
      ascertain the utility of devising system-wide policies and safety tools to
      improve neurosurgical practice.   Based on a review of the literature,
      thromboembolic events appeared to be the most common adverse events in
      endovascular neurosurgery, with a reported incidence ranging from 2% to 61%
      depending on aneurysm rupture status and mode of detection of the event.
      Intraprocedural and periprocedural prevention and rescue regimens are advocated
      to minimize this risk; however, evidence on the optimal use of anticoagulant and
      antithrombotic agents is limited. Furthermore, it is unknown what proportion of
      eligible patients receive any prophylactic treatment.   Groin-site hematoma is
      the most common access-related complication. Data from the cardiac literature
      indicate an overall incidence of 9% to 32%, but data specific to
      neuroendovascular therapy are scant. Manual compression, compression adjuncts,
      and closure devices are used with varying rates of success, but no standardized
      protocols have been tested on a broad scale. Contrast-induced nephropathy is one
      of the more common causes of hospital-acquired renal insufficiency, with an
      incidence of 30% in high-risk patients after contrast administration. Evidence
      from medical fields supports the use of various preventive strategies.  
      Intraprocedural vessel rupture is infrequent, with the reported incidence ranging
      from 1% to 9%, but it is potentially devastating. Improvements in device
      technology combined with proper endovascular technique play an important role in
      reducing this risk.   Occasionally, anatomical or technical difficulties preclude
      treatment of the lesion of interest. Reports of such occurrences are scant, but
      existing series suggest an incidence of 4% to 6%. Management strategies for
      radiation-induced effects are also discussed. The incidence rates are unknown,
      but protective techniques have been demonstrated.   Many of these complications
      have strategies that appear effective in reducing their risk of occurrence, but
      development and evaluation of systematic guidelines and protocols have been
      widely lacking. Furthermore, there has been little monitoring of levels of
      adherence to potentially effective practices. Protocols and monitoring programs
      to support integrated implementation may be broadly effective.

PMID- 23116095
TI  - Patterns in neurosurgical adverse events: open cerebrovascular neurosurgery.
AB  - OBJECT: As part of a project to devise evidence-based safety interventions for
      specialty surgery, we sought to review current evidence concerning the frequency
      of adverse events in open cerebrovascular neurosurgery and the state of knowledge
      regarding methods for their reduction. This review represents part of a series of
      papers written to consolidate information about these events and preventive
      measures as part of an ongoing effort to ascertain the utility of devising system
      wide policies and safety tools to improve neurosurgical practice. METHODS: The
      authors performed a PubMed search using search terms "cerebral aneurysm",
      "cerebral arteriovenous malformation", "intracerebral hemorrhage", "intracranial
      hemorrhage", "subarachnoid hemorrhage", and "complications" or "adverse events."
      Only papers that specifically discussed the relevant complication rates were
      included. Papers were chosen to be included to maximize the range of rates of
      occurrence for the reported adverse events. RESULTS: The review revealed
      hemorrhage-related hyperglycemia (incidence rates ranging from 27% to 71%) and
      cerebral salt-wasting syndromes (34%-57%) to be the most common perioperative
      adverse events related to subarachnoid hemorrhage (SAH). Next in terms of
      frequency was new cerebral infarction associated with SAH, with a rate estimated
      at 40%. Many techniques are advocated for use during surgery to minimize risk of
      this development, including intraoperative neurophysiological monitoring, but are
      not universally used due to surgeon preference and variable availability of
      appropriate staffing and equipment. The comparative effectiveness of using or
      omitting monitoring technologies has not been evaluated. The incidence of
      perioperative seizure related to vascular neurosurgery is unknown, but reported
      seizure rates from observational studies range from 4% to 42%. There are no
      standard guidelines for the use of seizure prophylaxis in these patients, and
      there remains a need for prospective studies to support such guidelines.
      Intraoperative rupture occurs at a rate of 7% to 35% and depends on aneurysm
      location and morphology, history of rupture, surgical technique, and surgeon
      experience. Preventive strategies include temporary vascular clipping. Technical
      adverse events directly involving application of the aneurysm clip include
      incomplete aneurysm obliteration and parent vessel occlusion. The rates of these
      events range from 5% to 18% for incomplete obliteration and 3% to 12% for major
      vessel occlusion. Intraoperative angiography is widely used to confirm clip
      placement; adjuncts include indocyanine green video angiography and microvascular
      Doppler ultrasonography. Use of these technologies varies by institution.
      DISCUSSION: A significant proportion of these complications may be avoidable
      through development and testing of standardized protocols to incorporate
      monitoring technologies and specific technical practices, teamwork and
      communication, and concentrated volume and specialization. Collaborative
      monitoring and evaluation of such protocols are likely necessary for the
      advancement of open cerebrovascular neurosurgical quality.

PMID- 23116096
TI  - Patterns in neurosurgical adverse events: intracranial neoplasm surgery.
AB  - OBJECT: Neurosurgery is a high-risk specialty currently undertaking the pursuit
      of systematic approaches to measuring and improving outcomes. As part of a
      project to devise evidence-based safety interventions for specialty surgery, the
      authors sought to review current evidence in cranial tumor resection concerning
      the frequency of adverse events in practice, their patterns, and current methods
      of reducing the occurrence of these events. This review represents part of a
      series of papers written to consolidate information about these events and
      preventive measures as part of an ongoing effort to ascertain the utility of
      devising system-wide policies and safety tools to improve neurosurgical practice.
      METHODS: The authors performed a PubMed search using search terms "intracranial
      neoplasm," "cerebral tumor," "cerebral meningioma," "glioma," and "complications"
      or "adverse events." Only papers that specifically discussed the relevant
      complication rates were included. Papers were chosen to maximize the range of
      rates of occurrence for the reported adverse events. RESULTS: Review of the tumor
      neurosurgery literature showed that documented overall complication rates ranged
      from 9% to 40%, with overall mortality rates of 1.5%-16%. There was a wide range
      of types of adverse events overall. Deep venous thromboembolism (DVT) was the
      most common adverse event, with a reported incidence of 3%-26%. The presence of
      new or worsened neurological deficit was the second most common adverse event
      found in this review, with reported rates ranging from 0% for the series of
      meningioma cases with the lowest reported rate to 20% as the highest reported
      rate for treatment of eloquent glioma. Benign tumor recurrence was found to be a
      commonly reported adverse event following surgery for intracranial neoplasms.
      Rates varied depending on tumor type, tumor location, patient demographics,
      surgical technique, the surgeon's level of experience, degree of specialization,
      and changes in technology, but these effects remain unmeasured. The incidence on
      our review ranged from 2% for convexity meningiomas to 36% for basal meningiomas.
      Other relatively common complications were dural closure-related complications
      (1%-24%), postoperative peritumoral edema (2%-10%), early postoperative seizure
      (1%-12%), medical complications (6%-7%), wound infection (0%-4%), surgery-related
      hematoma (1%-2%), and wrong-site surgery. Strategies to minimize risk of these
      events were evaluated. Prophylactic techniques for DVT have been widely
      demonstrated and confirmed, but adherence remains unstudied. The use of image
      guidance, intraoperative functional mapping, and real-time intraoperative MRI
      guidance can allow surgeons to maximize resection while preserving neurological
      function. Whether the extent of resection significantly correlates with improved
      overall outcomes remains controversial. DISCUSSION: A significant proportion of
      adverse events in intracranial neoplasm surgery may be avoidable by use of
      practices to encourage use of standardized protocols for DVT, seizure, and
      infection prophylaxis; intraoperative navigation among other steps; improved
      teamwork and communication; and concentrated volume and specialization.
      Systematic efforts to bundle such strategies may significantly improve patient
      outcomes.

PMID- 23116097
TI  - Neurosurgical checklists: a review.
AB  - Morbidity due to avoidable medical errors is a crippling reality intrinsic to
      health care. In particular, iatrogenic surgical errors lead to significant
      morbidity, decreased quality of life, and attendant costs. In recent decades
      there has been an increased focus on health care quality improvement, with a
      concomitant focus on mitigating avoidable medical errors. The most notable tool
      developed to this end is the surgical checklist. Checklists have been implemented
      in various operating rooms internationally, with overwhelmingly positive results.
      Comparatively, the field of neurosurgery has only minimally addressed the utility
      of checklists as a health care improvement measure. Literature on the use of
      checklists in this field has been sparse. Considering the widespread efficacy of
      this tool in other fields, the authors seek to raise neurosurgical awareness
      regarding checklists by reviewing the current literature.

PMID- 23116098
TI  - Creating a culture of safety within operative neurosurgery: the design and
      implementation of a perioperative safety video.
AB  - OBJECT: Surgical and medical errors result from failures in communication and
      handoffs as well as lack of standardization in clinical protocols and safety
      practices. Checklists, simulation training, and teamwork training have been shown
      to decrease adverse patient events and increase the safety culture of surgical
      teams. The goal of this project was to simplify and standardize perioperative
      patient safety practices and team communication processes within operative
      neurosurgery through the creation of an educational safety video targeted at a
      neurosurgical provider audience. METHODS: A multidisciplinary group consisting of
      neurosurgeons, anesthesiologists, nurses, neuromonitoring specialists, quality
      champions, and a professional video production company met over several months in
      an iterative process to 1) determine the overall objectives of the video, 2)
      decide on the content and format of the video, 3) modify the proposed content and
      format based on stakeholder feedback, and 4) record the video and complete final
      revisions during postproduction. RESULTS: The video was launched within the
      authors' institution in July 2012 in conjunction with ongoing research projects
      to study the effects of the video on 1) multidisciplinary providers' knowledge of
      perioperative safety practices, 2) provider safety attitudes and safety culture
      in the operating room, and 3) provider behavior in performing predetermined
      elements of the preoperative timeout and postoperative debrief. CONCLUSIONS: The
      neurosurgical perioperative safety video can serve as a national model for how
      quality champions can drive changes in safety culture and provider behavior among
      multidisciplinary perioperative patient care teams. Ongoing research is being
      performed to assess the impact of the video on provider knowledge, behavior, and
      safety attitudes and culture.

PMID- 23116099
TI  - Surgical debriefing: a reliable roadmap to completing the patient safety cycle.
AB  - Morbidity and mortality due to preventable medical errors are a disastrous
      reality in medicine. Debriefing, a process that allows individuals to discuss
      team performance in a constructive, supportive environment, has been linked to
      improved performance in various medical and surgical fields, including
      improvements in specific procedures, teamwork and communication, and error
      identification. However, the neurosurgical literature on this topic is limited.
      The authors review the debriefing literature in the field of medicine, with a
      specific emphasis on the operating room, and they report their own institutional
      experience with a debriefing module, from invention to pilot implementation, at
      Vanderbilt University Medical Center. The authors share the challenges and
      lessons learned from their quality improvement project. The field of neurosurgery
      would undoubtedly benefit from embracing debriefing, as its potential has been
      established in other medical specialties and can serve as a valuable role in
      immediately learning from mistakes. The authors hope that their colleagues can
      learn from this experience and improve their own.

PMID- 23116100
TI  - University of California, Los Angeles, surgical time-out process: evolution,
      challenges, and future perspective.
AB  - Since the development of the WHO Safe Surgery Saves Lives initiative and Surgical
      Safety Checklist, numerous hospitals across the globe have adopted the use of a
      surgical checklist. The UCLA Health System developed its first extended Surgical
      Safety Checklist in 2008. Authors of the present paper describe how the time-out
      checklist used before skin incision was implemented and how it progressed to its
      current form. Compliance with the most recent version of the checklist has been
      closely monitored via documentation and observance audits. In addition, the
      surgical team's appreciation of the current time-out has been assessed. Cultural,
      practice, and human resource challenges are discussed, as are potential future
      avenues for innovations in the emerging field of the surgical checklist in
      neurosurgery.

PMID- 23116101
TI  - "Team time-out" and surgical safety-experiences in 12,390 neurosurgical patients.
AB  - OBJECT: Quality and safety are basic concerns in any medical practice. Especially
      in daily surgical practice, with increasing turnover and shortened procedure
      times, attention to these topics needs to be assured. Starting in 2007, the
      authors used a perioperative checklist in all elective procedures and extended
      the checklist in January 2011 according to the so-called team time-out
      principles, with additional assessment of patient identity and the planned
      surgical procedure performed immediately before skin incision, including the
      emergency cases. METHODS: The advanced perioperative checklist includes parts for
      patient identification, preoperative assessments, team time-out, postoperative
      treatment, and imaging controls. All parts are signed by the responsible
      physician except for the team time-out, which is performed and signed by the
      theater nurse on behalf of the surgeon immediately before skin incision. RESULTS:
      Between January 2007 and December 2010, 1 wrong-sided bur hole in an emergency
      case and 1 wrong-sided lumbar approach in an elective case (of 8795 surgical
      procedures) occurred in the authors' department. Using the advanced perioperative
      checklist including the team time-out principles, no error occurred in 3595
      surgical procedures (January 2011-June 2012). In the authors' department all team
      members appreciate the chance to focus on the patient, the surgical procedure,
      and expected difficulties. The number of incomplete checklists and of patients
      not being transferred into the operating room was lowered significantly (p =
      0.002) after implementing the advanced perioperative checklist. CONCLUSIONS: In
      the authors' daily experience, the advanced perioperative checklist developed
      according to the team time-out principles improves preoperative workup and the
      focus of the entire team. The focus is drawn to the procedure, expected
      difficulties of the surgery, and special needs in the treatment of the particular
      patient. Especially in emergency situations, the team time-out synchronizes the
      involved team members and helps to improve patient safety.

PMID- 23116102
TI  - Application of an aviation model of incident reporting and investigation to the
      neurosurgical scenario: method and preliminary data.
AB  - OBJECT: Incident reporting systems are universally recognized as important tools
      for quality improvement in all complex adaptive systems, including the operating
      room. Nevertheless, introducing a safety culture among neurosurgeons is a slow
      process, and few studies are available in the literature regarding the
      implementation of an incident reporting system within a neurosurgical department.
      The authors describe the institution of an aviation model of incident reporting
      and investigation in neurosurgery, focusing on the method they have used and
      presenting some preliminary results. METHODS: In 2010, the Inpatient Safety On
      Board project was developed through cooperation between a team of human factor
      and safety specialists with aviation backgrounds (DgSky team) and the general
      manager of the Fondazione Istituto Neurologico Carlo Besta. In 2011, after
      specific training in safety culture, the authors implemented an aviation-derived
      prototype of incident reporting within the Department of Neurosurgery. They then
      developed an experimental protocol to track, analyze, and categorize any near
      misses that happened in the operating room. This project officially started in
      January 2012, when a dedicated team of assessors was established. All members of
      the neurosurgical department were asked to report near misses on a voluntary,
      confidential, and protected form (Patient Incident Reporting System form, Besta
      Safety Management Programme). Reports were entered into an online database and
      analyzed by a dedicated team of assessors with the help of a facilitator, and an
      aviation-derived root cause analysis was performed. RESULTS: Since January 2012,
      14 near misses were analyzed and classified. The near-miss contributing factors
      were mainly related to human factors (9 of 14 cases), technology (1 of 14 cases),
      organizational factors (3 of 14 cases), or procedural factors (1 of 14 cases).
      CONCLUSIONS: Implementing an incident reporting system is quite demanding; the
      process should involve all of the people who work within the environment under
      study. Persistence and strong commitment are required to enact the culture change
      essential in shifting from a paradigm of infallible operators to the philosophy
      of errare humanum est. For this paradigm shift to be successful, contributions
      from aviation and human factor experts are critical.

PMID- 23116103
TI  - Infection following operations on the central nervous system: deconstructing the
      myth of the sterile field.
AB  - Neurosurgical patients are at a high risk for infectious sequelae following
      operations. For neurosurgery in particular, the risk of surgical site infection
      has a unique implication given the proximity of the CSF and the CNS. Patient
      factors contribute to some degree; for example, cancer and trauma are often
      associated with impaired nutritional status, known risk factors for infection.
      Additionally, care-based factors for infection must also be considered, such as
      the length of surgery, the administration of steroids, and tissue
      devascularization (such as a craniotomy bone flap). When postoperative infection
      does occur, attention is commonly focused on potential lapses in surgical
      "sterility." Evidence suggests that the surgical field is not free of
      microorganisms. The authors propose a paradigm shift in the nomenclature of the
      surgical field from "sterile" to "clean." Continued efforts aimed at optimizing
      immune capacity and host defenses to combat potential infection are warranted.

PMID- 23116104
TI  - On the value of routine prothrombin time screening in elective neurosurgical
      procedures.
AB  - OBJECT: The authors performed a study to evaluate whether preoperative assessment
      of prothrombin time (PT) is mandatory in patients undergoing routinely planned
      neurosurgical procedures. METHODS: The charts of all patients admitted to general
      wards of the authors' department for routinely planned surgery (excluding trauma
      and ICU patients) between 2006 and 2010 were retrospectively reviewed. The
      authors assessed preoperative PT and the clinical courses of all patients, with
      special consideration for patients receiving coagulation factor substitution. All
      cases involving hemorrhagic complications were analyzed in detail with regard to
      pre- and postoperative PT abnormalities. Prothrombin time was expressed as the
      international normalized ratio, and values greater than 1.28 were regarded as
      elevated. RESULTS: Clinical courses and PT values of 4310 patients were reviewed.
      Of these, 33 patients (0.7%) suffered hemorrhagic complications requiring repeat
      surgery. Thirty-one patients (94%) had a normal PT before the initial operation,
      while 2 patients had slightly elevated PT values of 1.33 and 1.65, which were
      anticipated based on the patient's history. In the latter 2 cases, surgery was
      performed without prior correction of PT. Preoperatively, PT was elevated in 78
      patients (1.8%). In 73 (93.6%) of the 78 patients, the PT elevation was expected
      and explained by each patient's medical history. In only 5 (0.1%) of 4310
      patients did we find an unexpected PT elevation (mean 1.53, range 1.37-1.74). All
      5 patients underwent surgery without complications, while 2 had received
      coagulation factor substitution preoperatively, as requested by the surgeon,
      because of an estimated risk of bleeding complications. None of the 5 patients
      received coagulation factor substitution postoperatively, and later detailed
      laboratory studies ruled out single coagulation factor deficiencies. There was no
      statistically significant association between preoperatively elevated PT levels
      and the occurrence of hemorrhagic complications (p = 0.12). Before the second
      procedure but not before the initial operation, 4 (12%) of the 33 patients had
      elevated PT. CONCLUSIONS: The findings suggest that the value of preoperative PT
      testing is limited in patients in whom a normal history can be ascertained. Close
      postoperative PT control is necessary in every neurosurgical patient, and better
      tests need to be developed to identify patients who are prone to hemorrhagic
      complications.

PMID- 23116105
TI  - Introduction: quality process improvement and the neurosurgeon.

PMID- 23116106
TI  - Recent valves used for transluminal implantation in patients with aortic valve
      stenosis.
AB  - Aortic valve stenosis is becoming a burden to society due to the constantly aging
      population. After the onset of the first symptoms it usually follows an ominous
      route with high mortality levels even at two years without any medical
      intervention. The gold standard for treating aortic valve stenosis is surgical
      replacement; nonetheless, 30% of patients are left untreated due to increased
      risk of surgery. A less invasive method has been developed in the past decade,
      transcatheter aortic valve implantation (TAVI), which allows implantation of
      prosthesis in the native stenosed aortic valve position, using a catheter that
      enters the body in a transvascular way or through a minimal surgical cut down. In
      this review, we briefly discuss where the TAVI field begun, focus on the recent
      valves that are being used and finally look at what lies ahead. The review of the
      patents will assist in the understanding of how this field evolved, how it became
      established and what is to be expected in the future.

PMID- 23116108
TI  - Engineered inorganic nanoparticles for drug delivery applications.
AB  - Inorganic nanoparticles (NPs) currently have immense potential as drug delivery
      vectors due to their unique physicochemical properties such as high surface area
      per unit volume, their optical and magnetic uniqueness and the ability to be
      functionalized with a large number of ligands to enhance their affinity towards
      target molecules. These features, together with the therapeutic activity of some
      drugs, render the combination of these two entities (NP-drug) as an attractive
      alternative in the area of drug delivery. One of the major advantages of these
      conjugates is the possibility to have a local delivery of the drug, thus reducing
      systemic side effects and enabling a higher efficiency of the therapeutic
      molecule. This review highlights the direct implications of nanoscale particles
      in the development of drug delivery systems. In more detail, it is also remarked
      the extensive use of inorganic NPs for targeted cancer therapies. As the range of
      nanoparticles and their applications continues to increase, human safety concerns
      are gaining importance, which makes it necessary to better understand the
      potential toxicity hazards of these materials.

PMID- 23116109
TI  - An overview of ABC and SLC drug transporter gene regulation.
AB  - Membrane transporters play a significant role in drug absorption, distribution
      and excretion, and they consequently affect the pharmacokinetics, efficacy and
      safety of a drug. Under certain circumstances, such as pathological processes or
      exposure to certain substances, the expression of drug transporters is modified
      in cells. Change in transporter expression and function may affect cellular drug
      disposition resulting in different drug responses. This raises a number of
      questions such as which drugs are likely to modulate the expression of drug
      transporters, what factors support this process, and which transporters are
      influenced in a particular situation. In this paper, we summarize recent findings
      to find an answer to these questions. Particularly, we present an overview of the
      transcription factors involved in the regulation of a given drug transporter, the
      signaling transduction pathways that contribute to drug transporter gene
      expression, and xenobiotics and endobiotics that initiate the processes.

PMID- 23116110
TI  - Electroporation in DNA vaccination protocols against cancer.
AB  - Since conventional therapeutic approaches in cancer are highly invasive they
      hardly prolong patient survival for more than few months. Having the ability to
      stimulate both cellular and humoural immune responses, immunisation with naked
      plasmid DNA encoding tumour-associated antigens or tumour-specific antigens has
      recently reported a plethora of advantages, and the improvement of vaccine
      efficacy has emerged as a goal in the development of DNA vaccination as anti
      tumour therapy. Nevertheless, because of their poor immunogenicity when
      administered as unformulated intramuscular injections, plasmid DNA vaccines need
      to be improved. Recent data suggest that the DNA vaccine efficacy may
      significantly be increased by electroporation. This review highlights the recent
      literature that supports electroporation as an effective strategy to improve DNA
      based vaccination protocols, investigating the most relevant studies, recently
      developed for the applications of DNA vaccine electrotransfer against tumours in
      pre-clinical and clinical studies.

PMID- 23116111
TI  - Advances in photodynamic therapy assisted by electroporation.
AB  - Low invasive therapies of cancer are directed toward the methods that target
      selectively on carcinoma cells. Photodynamic therapy (PDT) is a therapeutic
      modality in which combination of a photosensitizer, light, and oxygen renders
      reactive oxygen species (ROS) which cause damage to a tumor tissue. Each of these
      factors is not toxic in itself and the effect of therapy results from high uptake
      of a photosensitizer by carcinoma cells and directed tumor irradiation by light.
      Realization of the therapy depends on efficient transport of the photosensitizer
      across the membrane and intracellular accumulation of the drug. Depending on the
      treatment conditions and the uptake mechanism, sensitizers can potentially reach
      different intracellular concentrations and different cellular effects can be
      triggered. Transport efficacy can be significantly augmented by applying electric
      pulses to plasma membrane, which opens transient non-selective hydrophilic
      nanopores as additional pathways across lipid membranes. Electroporation (EP) has
      been utilized to facilitate drug uptake in electrochemotherapy (ECT) and has been
      tested in combination with PDT. In the review, we described effects of PDT and
      electrophotodynamic therapy (EPDT) on carcinoma and healthy cells, studied in
      vitro and vivo. The comparison of different drugs has been applied to tests
      considering the enhancement of their cytotoxicity, selectivity, and additional
      effects caused by electroporation.

PMID- 23116112
TI  - Stem cell lineage commitment by electrical fields and the potential application
      in drug discovery.
AB  - Stem cells may be applied to improve the efficiency of drug discovery, but more
      effective protocols are first required to control the differentiation. Recent
      researches have revealed that physical stimulation is an important avenue for
      stem cell lineage commitment, such as electrical field stimulation. Here, we
      review literatures about stem cell differentiation by electrical field
      stimulation. Various forms of electrical fields with soluble induction factors
      have shown to produce a synergistic effect in order to enhance the osteogenic
      commitment. Moreover, electrical field stimulation alone shows marked effects of
      pre-commitment to cardiomyocyte and neuron. However, the related precise
      molecular regulatory mechanism is unclear. As cardiomyocyte and neuron are
      crucial factors in drug development process, electrical field stimulation may be
      proposed as an effect important for stem cell differentiation, exhibiting a
      potential application in drug discovery.

PMID- 23116113
TI  - In vivo DNA electrotransfer for immunotherapy of cancer and neurodegenerative
      diseases.
AB  - Electroporation is the process commonly referred to the transient increase in the
      permeability of cell membranes on submission to electric field pulses.
      Electroporation has become an increasingly extensive method to enhance in vivo
      DNA delivery for both gene therapy applications as well as for delivery of DNA
      vaccines, mostly against cancer. In vivo gene electrotransfer is of special
      interest since it is the most efficient non-viral strategy for gene delivery and
      it is worthy of low manufacturing costs, ease of realization and favorable safety
      profile. No adverse findings observed in toxicology and
      biodistribution/integration studies have been warranted for the evaluation of
      this approach in humans. Therefore, gene delivery followed by electroporation is
      currently being investigated in several clinical trials. The positive outcomes of
      early studies suggest that the efficacy of gene delivery and immunogenicity has
      greatly improved by electroporation. This review briefly summarizes salient
      features and recent findings that have contributed to the rapid progress of
      electroimmunotherapy as well as an overview of advanced clinical studies in
      oncology. Translation of in vivo DNA electrovaccination for neurodegenerative
      diseases as well as future expectations are also discussed.

PMID- 23116114
TI  - Nucleic acids electro-transfer: from bench to bedside.
AB  - There are a number of stigmas attached to the development of antitumor drugs such
      as their safe and efficient delivery into target cells or tissues. The one such
      case is that of macromolecules, such as nucleic acids where it poses severe
      limits. From this point of view, electro-pulsation proves to be a promising
      method for cancer-associated gene therapy. It involves the direct application of
      electric pulses on cells or tissues which leads to a transient permeabilization
      of their plasma membrane allowing efficient in vitro and in vivo delivery of
      exogenous molecules. The present review probes the electrotransfer of nucleic
      acids, the nature of nucleic acids (plasmid DNA, mRNA, siRNA, LNA...) which can
      be electrotransferred and the mechanism of their electrotransfer.

PMID- 23116115
TI  - Gene transfer and drug delivery with electric pulse generators.
AB  - Electroporation is a process that involves a series of intense electric pulses
      used to overcome the barrier of the cell membrane. The application of an external
      electric field may result in reversible breakdown of cell membrane. This
      transient state helps to introduce cells with a variety of different molecules,
      such as DNA and drug molecules, and is known as the fundamental mechanisms of
      gene transfer and drug delivery with electric pulses. This paper reviews (1) the
      utility of electric pulse generators in gene transfer and drug delivery, (2)
      development of electric pulse generators for utilizing them in gene transfer and
      drug delivery, (3) study of parameters of electric pulses used in gene transfer
      and drug delivery, (4) study of electrode configurations used in gene transfer
      and drug delivery.

PMID- 23116116
TI  - Electroporation for drug and gene delivery in cancer therapy.

PMID- 23116117
TI  - Structural parameters governing the dynamic combinatorial synthesis of catenanes
      in water.
AB  - We report the first dynamic combinatorial synthesis in water of an all-acceptor
      [2]catenane and of different types of donor-acceptor [2] and [3]catenanes.
      Linking two electron-deficient motifs within one building block using a series of
      homologous alkyl chains provides efficient and selective access to a variety of
      catenanes and offers an unprecedented opportunity to explore the parameters that
      govern their synthesis in water. In this series, catenane assembly is controlled
      by a fine balance between kinetics and thermodynamics and subtle variations in
      the building block structure, such as the linker length and building block
      chirality. A remarkable and unexpected odd-even effect with respect to the number
      of atoms in the alkyl linker is reported.

PMID- 23116118
TI  - Development of a Gd(III)-based receptor-induced magnetization enhancement (RIME)
      contrast agent for beta-glucuronidase activity profiling.
AB  - beta-Glucuronidase is a key lysosomal enzyme and is often overexpressed in
      necrotic tumor masses. We report here the synthesis of a pro receptor-induced
      magnetization enhancement (pro-RIME) magnetic resonance imaging (MRI) contrast
      agent ([Gd(DOTA-FPbetaGu)]) for molecular imaging of beta-glucuronidase activity
      in tumor tissues. The contrast agent consists of two parts, a gadolinium complex
      and a beta-glucuronidase substrate (beta-d-glucopyranuronic acid). The binding
      association constant (KA) of [Gd(DOTA-FPbetaGu)] is 7.42 * 10(2), which is
      significantly lower than that of a commercially available MS-325 (KA = 3.0 *
      10(4)) RIME contrast agent. The low KA value of [Gd(DOTA-FPbetaGu)] is due to the
      pendant beta-d-glucopyranuronic acid moiety. Therefore, [Gd(DOTA-FPbetaGu)] can
      be used for detection of beta-glucuronidase through RIME modulation. The detail
      mechanism of enzymatic activation of [Gd(DOTA-FPbetaGu)] was elucidated by LC-MS.
      The kinetics of beta-glucuronidase catalyzed hydrolysis of [Eu(DOTA-FPbetaGu)] at
      pH 7.4 best fit the Miechalis-Menten kinetic mode with Km = 1.38 mM, kcat = 3.76
      * 10(3), and kcat/Km = 2.72 * 10(3) M(-1) s(-1). The low Km value indicates high
      affinity of beta-glucuronidase for [Gd(DOTA-FPbetaGu)] at physiological pH.
      Relaxometric studies revealed that T1 relaxivity of [Gd(DOTA-FPbetaGu)] changes
      in response to the concentration of beta-glucuronidase. Consistent with the
      relaxometric studies, [Gd(DOTA-FPbetaGu)] showed significant change in MR image
      signal in the presence of beta-glucuronidase and HSA. In vitro and in vivo MR
      images demonstrated appreciable differences in signal enhancement in the cell
      lines and tumor xenografts in accordance to their expression levels of beta
      glucuronidase. 

PMID- 23116120
TI  - Poly(N-vinylpyrrolidone)-block-poly(vinyl acetate) as a drug delivery vehicle for
      hydrophobic drugs.
AB  - Poly((N-vinylpyrrolidone)-block-poly(vinyl acetate)) (PVP-b-PVAc) block
      copolymers of varying molecular weight and hydrophobic block lengths were
      synthesized via controlled radical polymerization and investigated as carriers
      for the solubilization of highly hydrophobic riminophenazine compounds. These
      compounds have recently been shown to exhibit a strong activity against a variety
      of cancer types. PVP-b-PVAc self-assembles into polymer vesicles in aqueous
      media, and the dialysis method was used to load the water-insoluble drug
      (clofazimine) into these polymer vesicles. The polymer vesicles were
      characterized by 1H NMR spectroscopy to confirm vesicle formation and the
      incorporation of the anticancer drugs into the polymer vesicles. Dynamic light
      scattering was used to determine the particle size and particle size distribution
      of the drug-loaded vesicles as well as the stability of the vesicles under
      physiological conditions. The size of the polymer vesicles did not increase upon
      loading with clofazimine, and the particle size of 180-200 nm and the narrow
      particle size distribution were maintained. The morphology of the vesicles was
      examined by transmission electron microscopy. The polymer vesicles had a
      relatively high drug loading capacity of 20 wt %. In vitro cytotoxicity studies
      of PVP-b-PVAc and drug-loaded PVP-b-PVAc were performed against MDA-MB-231
      multidrug-resistant breast epithelial cancer cells and MCF12A nontumorigenic
      breast epithelial cells. In vitro experiments demonstrated that the PVP-b-PVAc
      drug carrier showed no cytotoxicity, which confirms the biocompatibility of the
      PVP-b-PVAc drug carrier. The results indicate that the present PVP-b-PVAc block
      copolymer could be a potential candidate as a drug carrier for hydrophobic drugs.

PMID- 23116119
TI  - Serine phosphorylation is critical for the activation of ubiquitin-specific
      protease 1 and its interaction with WD40-repeat protein UAF1.
AB  - Deubiquitinating enzymes (DUBs) are important for the normal function of a number
      of cellular processes, including transcriptional regulation, cell cycle control,
      and DNA damage response. The enzymatic activity of DUB is regulated by different
      mechanisms. DUBs in several different families are post-translationally modified
      by phosphorylation. Large-scale phosphoproteomic studies of human DUBs revealed
      that a majority of ubiquitin-specific proteases (USPs) are phosphorylated. USP1
      is a prototypical DUB that requires a specific interaction with a WD40-repeat
      protein, UAF1, for its catalytic activity. In this study, we show that Ser313
      phosphorylation in USP1 is required for its interaction with UAF1 and for the
      stimulation of USP1's activity. In contrast, two other known USP1 serine
      phosphorylations (Ser42 and Ser67) are dispensable with respect to the activity
      of the USP1/UAF1 complex. An S313D phosphomimetic mutation in USP1 can substitute
      for Ser313 phosphorylation in promoting the formation of the USP1/UAF1 complex.
      We further demonstrated that CDK1 is responsible for Ser313 phosphorylation, and
      protein phosphatase treatment of USP1 can lead to inactivation of USP1/UAF1. An
      inserted domain in USP1 (amino acids 235-408) was found to interact with UAF1,
      and this interaction is mediated by Ser313 phosphorylation. Our findings revealed
      an intriguing mechanism of regulating USP1 activity that combines phosphorylation
      of a key serine residue in USP1 and the specific interaction of USP1 with a WD40
      repeat protein UAF1. The pSer313-dependent formation of the USP1/UAF1 complex
      points to a new approach for inhibiting USP1 activity by disrupting the
      interaction between the UAF1's WD40-repeat domain and the Ser313-containing
      phosphopeptide in USP1.

PMID- 23116121
TI  - Size effects of pore density and solute size on water osmosis through nanoporous
      membrane.
AB  - Understanding the behavior of osmotic transport across nanoporous membranes at
      molecular level is critical to their design and applications, and it is also
      beneficial to the comprehension of the mechanism of biological transmembrane
      transport processes. Pore density is an important parameter for nanoporous
      membranes. To better understand the influence of pore density on osmotic
      transport, we have performed systematic molecular dynamics simulations on water
      osmosis across nanoporous membranes with different pore densities (i.e., number
      of pores per unit area of membrane). The simulation results reveal that
      significant size effects occur when the pore density is so high that the center
      to-center distance between neighboring nanopores is comparable to the solute
      size. The size effects are independent of the pore diameter and solute
      concentration. A simple quantitative correlation between pore density, solute
      size, and osmotic flux has been established. The results are excellently
      consistent with the theoretical predictions. It is also shown that solute
      hydration plays an important role in real osmotic processes. Solute hydration
      strengthens the size effects of pore density on osmotic processes due to the
      enlarged effective solute size induced by hydration. The influence of pore
      density, solute size, and solute hydration on water osmosis through nanoporous
      membranes can be introduced to eliminate the deviations of real osmotic processes
      from ideal behavior.

PMID- 23116123
TI  - Understanding the linkages between informal and formal care for people living
      with HIV in sub-Saharan Africa.
AB  - In response to the human resource challenges facing African health systems, there
      is increasing involvement of informal care providers in HIV care. Through social
      and institutional interactions that occur in the delivery of HIV care, linkages
      between formal and informal systems of care often emerge. Based on a review of
      studies documenting the relationships between formal and informal HIV care in sub
      Saharan Africa, we suggest that linkages can be conceptualised as either 'actor
      oriented' or 'systems-oriented'. Studies adopting an actor-oriented focus examine
      hierarchical working relationships and communication practices among health
      systems actors, while studies focusing on systems-oriented linkages document the
      presence, absence or impact of formal inter-institutional partnership agreements.
      For linkages to be effective, the institutional frameworks within which linkages
      are formalised, as well as the ground-level interactions of those engaged in
      care, ought to be considered. However, to date, both actor- and system-oriented
      linkages appear to be poorly utilised by policy makers to improve HIV care. We
      suggest that linkages between formal and informal systems of care be considered
      across health systems, including governance, human resources, health information
      and service delivery in order to improve access to HIV services, enable knowledge
      transfer and strengthen health systems.

PMID- 23116125
TI  - Reoperation and patient satisfaction after the Mobility total ankle arthroplasty.
AB  - BACKGROUND: The purpose of the present study was to report on the frequency of
      reoperation, failure and patient satisfaction after the Mobility total ankle
      arthroplasty. METHODS: Sixty-two consecutive primary total ankle arthroplasties
      in 60 patients were performed with the use of the DePuy Mobility total ankle
      system between February 2006 and January 2009. Fifty-eight ankles in 56 patients
      were followed up between 14 and 49 months (mean: 32 months). RESULTS: Eighteen
      ankles (31%) underwent an initial reoperation at a mean time of 14 months after
      primary total ankle arthroplasty. Only three ankles (17%) had improved symptoms
      after initial reoperation. Eight of these 18 ankles (44%) underwent a second
      reoperation. A total of seven ankles (12%) had been revised. Overall, 67% were
      satisfied, and 79% stated that they would undergo the same operation again.
      DISCUSSION: This study on a third-generation total ankle arthroplasty reported a
      relatively high rate of reoperation. There was a significant increase in the
      reported failure when using re-operation rather than component revision as the
      end point. This may be one of the inherent limitations in Joint Registry data
      that only include component revision.

PMID- 23116124
TI  - Design, synthesis, and biological evaluation of 17-cyclopropylmethyl-3,14beta
      dihydroxy-4,5alpha-epoxy-6beta-[(4'-pyridyl)carboxamido]morphinan derivatives as
      peripheral selective MU opioid receptor Agents.
AB  - Peripheral selective MU opioid receptor (MOR) antagonists could alleviate the
      symptoms of opioid-induced constipation (OIC) without compromising the analgesic
      effect of opioids. However, a variety of adverse effects were associated with
      them, partially due to their relatively low MOR selectivity. NAP, a 6beta-N-4'
      pyridyl substituted naltrexamine derivative, was identified previously as a
      potent and highly selective MOR antagonist mainly acting within the peripheral
      nervous system. The noticeable diarrhea associated with it prompted the design
      and synthesis of its analogues in order to study its structure-activity
      relationship. Among them, compound 8 showed improved pharmacological profiles
      compared to the original lead, acting mainly at peripheral while increasing the
      intestinal motility in morphine-pelleted mice (ED(50) = 0.03 mg/kg). The slight
      decrease of the ED(50) compared to the original lead was well compensated by the
      unobserved adverse effect. Hence, this compound seems to be a more promising lead
      to develop novel therapeutic agents toward OIC.

PMID- 23116126
TI  - Comparing the accuracy of brief versus long depression screening instruments
      which have been validated in low and middle income countries: a systematic
      review.
AB  - BACKGROUND: Given the high prevalence of depression in primary health care (PHC),
      the use of screening instruments has been recommended. Both brief and long
      depression screening instruments have been validated in low and middle income
      countries (LMIC), including within HIV care settings. However, it remains unknown
      whether the brief instruments validated in LMIC are as accurate as the long ones.
      METHODS: We conducted a search of PUBMED, the COCHRANE library, AIDSLINE, and
      PSYCH-Info from their inception up to July 2011, for studies that validated
      depression screening instruments in LMIC. Data were extracted into tables and
      analyzed using RevMan 5.0 and STATA 11.2 for the presence of heterogeneity.
      RESULTS: Nineteen studies met our inclusion criteria. The reported prevalence of
      depression in LMIC ranged from 11.1 to 53%. The area under curve (AUC) scores of
      the validated instruments ranged from 0.69-0.99. Brief as well as long screening
      instruments showed acceptable accuracy (AUC>=0.7). Five of the 19 instruments
      were validated within HIV settings. There was statistically significant
      heterogeneity between the studies, and hence a meta-analysis could not be
      conducted to completion. Heterogeneity chi-squared = 189.23 (d.f. = 18) p<.001.
      CONCLUSION: Brief depression screening instruments in both general and HIV-PHC
      are as accurate as the long ones. Brief scales may have an edge over the longer
      instruments since they can be administered in a much shorter time. However,
      because the ultra brief scales do not include the whole spectrum of depression
      symptoms including suicide, their use should be followed by a detailed diagnostic
      interview.

PMID- 23116127
TI  - Complement activation in thrombotic microangiopathies.

PMID- 23116128
TI  - Nexa: a scalable neural simulator with integrated analysis.
AB  - Large-scale neural simulations encompass challenges in simulator design, data
      handling and understanding of simulation output. As the computational power of
      supercomputers and the size of network models increase, these challenges become
      even more pronounced. Here we introduce the experimental scalable neural
      simulator Nexa, for parallel simulation of large-scale neural network models at a
      high level of biological abstraction and for exploration of the simulation
      methods involved. It includes firing-rate models and capabilities to build
      networks using machine learning inspired methods for e.g. self-organization of
      network architecture and for structural plasticity. We show scalability up to the
      size of the largest machines currently available for a number of model scenarios.
      We further demonstrate simulator integration with online analysis and real-time
      visualization as scalable solutions for the data handling challenges.

PMID- 23116129
TI  - Dissemination of panton-valentine leukocidin-positive methicillin-resistant
      Staphylococcus aureus in Okinawa, Japan.
AB  - Panton-Valentine leukocidin (PVL) is a pore-forming cytotoxin that is produced by
      Staphylococcus aureus closely associated with skin and soft-tissue infections
      (SSTI). PVL-positive S. aureus strains have been identified worldwide, including
      in the USA; however, few studies have reported the presence of these strains in
      Japan. In this study, we prospectively investigated the prevalence of PVL in S.
      aureus strains from outpatients presenting with SSTI in Okinawa and characterized
      the PVL-positive S. aureus strains by polymerase chain reaction (PCR) and
      multilocus sequence typing (MLST). From 2008-2010, 499 clinical samples were
      obtained from 497 people. S. aureus was identified in 274 samples, and 36% (99 of
      274) were methicillin-resistant S. aureus (MRSA). Seventeen (6.2%) PVL-positive
      S. aureus strains were detected by PCR, and 12 of the 17 PVL-positive strains
      were MRSA. Most PVL-positive S. aureus caused furuncles or carbuncles. Nine of
      the 17 PVL-positive isolates had an ST8 MRSA genotype and most harbored SCCmec
      type IVa and the arcA gene of the arginine catabolic mobile element, which is
      identical to the USA300 clone prevalent in the USA. PVL-positive S. aureus
      strains were more likely to be resistant to erythromycin (65%) and levofloxacin
      (53%). PVL-positive S. aureus strains have emerged and are spreading as a
      causative pathogen for SSTI in Okinawa.

PMID- 23116130
TI  - Quality of life profile and psychometric properties of the EQ-5D-5L in HIV/AIDS
      patients.
AB  - OBJECTIVES: We assessed health-related quality of life (HRQOL), its associated
      factors, and examined measurement properties of the EuroQol - 5 Dimensions - 5
      Levels (EQ-5D-5L) in HIV/AIDS patients. METHODS: A cross-sectional multi-site
      survey was conducted in 1016 patients (age: 35.4 +/- 7.0 years; 63.8% male) in
      three epicenters of Vietnam. Internal consistency reliability, convergent
      validity, and discriminative validity of the EQ-5D-5L and a visual analogue scale
      (VAS) were evaluated. Tobit censored regression models were used to identify
      predictors of HRQOL in HIV/AIDS patients. RESULTS: The mean EQ-5D-5L single index
      and VAS were 0.65 (95% Confidence Interval (CI) = 0.63; 0.67) and 70.3 (95% CI =
      69.2; 71.5). Cronbach's alpha of five dimensions was 0.85. EQ-5D-5L has a good
      convergent validity with VAS (0.73). It discriminated patients at different
      HIV/AIDS stages, duration of ART, and CD4 cell count. Predictors of poorer HRQOL
      included being female, lower education level, unemployment, alcohol and drug use,
      CD4<200 cells/mL, and advanced HIV/AIDS stages. CONCLUSION: The EQ-5D-5L has good
      measurement properties in HIV/AIDS patients and holds potentials for monitoring
      ART outcomes. Integration of HRQOL measurement using EQ-5D-5L in HIV/AIDS
      clinical practice could be helpful for economic evaluation of HIV/AIDS
      interventions.

PMID- 23116131
TI  - Combining proteomics and transcriptome sequencing to identify active plant-cell
      wall-degrading enzymes in a leaf beetle.
AB  - BACKGROUND: The primary plant cell wall is a complex mixture of polysaccharides
      and proteins encasing living plant cells. Among these polysaccharides, cellulose
      is the most abundant and useful biopolymer present on earth. These
      polysaccharides also represent a rich source of energy for organisms which have
      evolved the ability to degrade them. A growing body of evidence suggests that
      phytophagous beetles, mainly species from the superfamilies Chrysomeloidea and
      Curculionoidea, possess endogenous genes encoding complex and diverse families of
      so-called plant cell wall degrading enzymes (PCWDEs). The presence of these genes
      in phytophagous beetles may have been a key element in their success as
      herbivores. Here, we combined a proteomics approach and transcriptome sequencing
      to identify PCWDEs present in larval gut contents of the mustard leaf beetle,
      Phaedon cochleariae. RESULTS: Using a two-dimensional proteomics approach, we
      recovered 11 protein bands, isolated using activity assays targeting cellulose-,
      pectin- and xylan-degrading enzymes. After mass spectrometry analyses, a total of
      13 proteins putatively responsible for degrading plant cell wall polysaccharides
      were identified; these proteins belong to three glycoside hydrolase (GH)
      families: GH11 (xylanases), GH28 (polygalacturonases or pectinases), and GH45
      (beta-1,4-glucanases or cellulases). Additionally, highly stable and proteolysis
      resistant host plant-derived proteins from various pathogenesis-related protein
      (PRs) families as well as polygalacturonase-inhibiting proteins (PGIPs) were also
      identified from the gut contents proteome. In parallel, transcriptome sequencing
      revealed the presence of at least 19 putative PCWDE transcripts encoded by the P.
      cochleariae genome. All of these were specifically expressed in the insect gut
      rather than the rest of the body, and in adults as well as larvae. The
      discrepancy observed in the number of putative PCWDEs between transcriptome and
      proteome analyses could be partially explained by differences in transcriptional
      level. CONCLUSIONS: Combining proteome and transcriptome sequencing analyses
      proved to be a powerful tool for the discovery of active PCWDEs in a non-model
      species. Our data represent the starting point of an in-depth functional and
      evolutionary characterization of PCWDE gene families in phytophagous beetles and
      their contribution to the adaptation of these highly successful herbivores to
      their host plants.

PMID- 23116132
TI  - Glucose induces autophagy under starvation conditions by a p38 MAPK-dependent
      pathway.
AB  - Autophagy is a natural process of 'self-eating' that occurs within cells and can
      be either pro-survival or can cause cell death. As a pro-survival mechanism,
      autophagy obtains energy by recycling cellular components such as macromolecules
      or organelles. In response to nutrient deprivation, e.g. depletion of amino acids
      or serum, autophagy is induced and most of these signals converge on the kinase
      mTOR (mammalian target of rapamycin). It is commonly accepted that glucose
      inhibits autophagy, since its deprivation from cells cultured in full medium
      induces autophagy by a mechanism involving AMPK (AMP-activated protein kinase),
      mTOR and Ulk1. However, we show in the present study that under starvation
      conditions addition of glucose produces the opposite effect. Specifically, the
      results of the present study demonstrate that the presence of glucose induces an
      increase in the levels of LC3 (microtubule-associated protein 1 light chain)-II,
      in the number and volume density of autophagic vacuoles and in protein
      degradation by autophagy. Addition of glucose also increases intracellular ATP,
      which is in turn necessary for the induction of autophagy because the glycolysis
      inhibitor oxamate inhibits it, and there is also a good correlation between LC3
      II and ATP levels. Moreover, we also show that, surprisingly, the induction of
      autophagy by glucose is independent of AMPK and mTOR and mainly relies on p38
      MAPK (mitogen-activated protein kinase).

PMID- 23116133
TI  - Synthesis of monolysyl advanced glycation endproducts and their incorporation
      into collagen model peptides.
AB  - The synthesis of advanced glycation endproducts (AGEs), CML, CEL, and pyrraline
      and their incorporation into collagen model peptides is reported. AGEs are
      modified amino acids that form on proteins such as collagen and are thought to
      play a significant role in the pathogenesis of many diseases, particularly
      diabetes. The synthesis and incorporation of these compounds into synthetic
      peptides is a key step in developing model systems with which to investigate AGE
      modified proteins.

PMID- 23116134
TI  - Narboh D, a respiratory burst oxidase homolog in Nicotiana attenuata, is required
      for late defense responses after herbivore attack.
AB  - The superoxide (O2-)-generating NADPH oxidases are crucial for the defense of
      plants against attack from pathogens; however, it remains unknown whether they
      also mediate responses against chewing insect herbivores. The transcripts of the
      respiratory burst NADPH oxidase homolog Narboh D in Nicotiana attenuate are
      rapidly and transiently elicited by wounding, and are amplified when Manduca
      sexta oral secretions (OS) are added to the wounds. The fatty-acid-amino-acid
      conjugates (FACs), demonstrably the major elicitors in M. sexta OS, are
      responsible for the increase in Narboh D transcripts. Silencing Narboh D
      significantly reduced reactive oxygen species (ROS) levels after OS elicitation,
      but neither OS-elicited jasmonic acid (JA) or JA-isoleucine (JA-Ile) bursts,
      pivotal hormones that regulates plant resistance to herbivores, nor early
      transcripts of herbivore defense-related genes (NaJAR4 and NaPAL1), were
      influenced. However, late OS-elicited increases in trypsin proteinase inhibitors
      (TPIs), as well as the transcript levels of defense genes such as polyphenol
      oxidase, TPI and Thionin were significantly reduced. In addition, Narboh D
      silenced plants were more vulnerable to insect herbivores, especially the larvae
      of the generalist Spodoptera littoralis. We thus conclude that Narboh D-based
      defenses play an important role in late herbivore-elicited responses.

PMID- 23116135
TI  - General report & recommendations in predictive, preventive and personalised
      medicine 2012: white paper of the European Association for Predictive, Preventive
      and Personalised Medicine.
AB  - This report is the collective product of word-leading experts working in the
      branches of integrative medicine by predictive, preventive and personalised
      medicine (PPPM) under the coordination of the European Association for
      Predictive, Preventive and Personalised Medicine. The general report has been
      prepared as the consortium document proposed at the EPMA World Congress 2011
      which took place in Bonn, Germany. This forum analyzed the overall deficits and
      trends relevant for the top-science and daily practice in PPPM focused on the
      patient. Follow-up consultations resulted in a package of recommendations for
      consideration by research units, educators, healthcare industry, policy-makers,
      and funding bodies to cover the current knowledge deficit in the field and to
      introduce integrative approaches for advanced diagnostics, targeted prevention,
      treatments tailored to the person and cost-effective healthcare.

PMID- 23116136
TI  - Total synthesis of aeruginosin 98B.
AB  - The first total synthesis of aeruginosin 98B was accomplished. The key step is a
      highly diastereoselective Pd-catalyzed intramolecular asymmetric allylic
      alkylation reaction of a diastereomeric mixture of allylic carbonates that is
      enabled by the use of racemic phosphine ligand L1.

PMID- 23116137
TI  - Bisulfite-driven autocatalysis in the bromate-thiosulfate reaction in a slightly
      acidic medium.
AB  - The thiosulfate-bromate reaction has been studied by high-performance liquid
      chromatography, monitoring the concentrations of thiosulfate and tetrathionate
      simultaneously. It is found that concentration-time curves of both species
      display a sigmoidal shape in a slightly acidic, well-buffered medium. Unlike the
      previously reported complex reaction systems involving bromate, this nonlinear
      dynamical behavior originates from neither proton nor bromine(III) autocatalysis
      under our experimental conditions. We demonstrated that sulfur(IV) species
      significantly accelerates the reaction; therefore, it acts as an autocatalyst. To
      the best of our knowledge, no reaction system has yet been reported among the pH
      driven oxysulfur-oxyhalogen systems, where sulfur(IV) has such a remarkable role.
      On the basis of the simultaneous evaluation of [S2O3(2-)] and [S4O6(2-)] time
      series, an eight-step kinetic model is proposed to account for the experimental
      observations. The model employed here may serve as a solid starting point to
      extend it for other oxysulfur-oxyhalogen systems where such a seemingly general
      phenomenon may become observable. 

PMID- 23116138
TI  - Diffusion, molecular separation, and drug delivery from lipid mesophases with
      tunable water channels.
AB  - Lyotropic liquid crystals characterized by a bicontinuous cubic phase (BCP) have
      a structure characterized by interpenetrated water channels following triply
      periodic minimal surfaces, which can be stable in excess water conditions and
      thus suitable in a multitude of applications. The control of the water channels
      size in these systems has a direct impact on their use for drug delivery,
      crystallization, and membrane separation processes. In this work we carry out
      systematic diffusion studies to show how the control on the water channel
      dimensions directly correlates with the release and separation performance of
      bicontinuous cubic phases. Specifically, we tune the water channels diameter of
      the monolinolein/water system by adding different amounts of sucrose stearate,
      which, having hydration-enhancing properties, can shift the boundaries of the
      phase diagram. We then design a model bicontinuous cubic phase lipidic membrane
      of the Im3m space group, having a sugar ester to monolinolein ratio of 20%, and
      we follow the diffusion within its water channels, by using molecules that differ
      systematically in size and molecular conformation, and we demonstrate, for each
      class of molecules, a diffusion-enhanced process upon increase of the water
      channel diameter. Finally, we also show the ability of the bicontinuous cubic
      phase to efficiently and selectively separate nanoparticles of a target size, by
      choosing an amount of sucrose stearate for which the water channel diameter and
      the nanoparticle dimensions match, demonstrating the possible use of these
      systems as filtering membranes of tunable molecular cutoff.

PMID- 23116139
TI  - Electronic and magnetic properties of manganese and iron atoms decorated with BO2
      superhalogens.
AB  - Using density functional theory based calculations, we have systematically
      studied the equilibrium geometries, relative stabilities, and electronic and
      magnetic properties of Fe and Mn atoms interacting with a varying number of BO(2)
      moieties. These clusters are found to exhibit hyperhalogen behavior with electron
      affinities as high as 6.9 eV once the number of BO(2) moieties exceed the nominal
      valences of these transition metals toms, namely 2 for both Fe and Mn. In all
      cases the transition metal atoms retain a sizable spin magnetic moment, even
      exceeding their free atom values at certain compositions. We also note that when
      more than two BO(2) moieties are bound to neutral Fe and Mn atoms, they tend to
      dimerize. In the case of negative ions, this process occurs at n >= 3, thus
      leading to different neutral and anionic ground state geometries. The effect of
      these structural changes in the interpretation of photoelectron spectroscopy
      experiments is discussed.

PMID- 23116140
TI  - Chitosan microneedle patches for sustained transdermal delivery of
      macromolecules.
AB  - This paper introduces a chitosan microneedle patch for efficient and sustained
      transdermal delivery of hydrophilic macromolecules. Chitosan microneedles have
      sufficient mechanical strength to be inserted in vitro into porcine skin at
      approximately 250 MUm in depth and in vivo into rat skin at approximately 200 MUm
      in depth. Bovine serum albumin (BSA, MW=66.5 kDa) was used as a model protein to
      explore the potential use of chitosan microneedles as a transdermal delivery
      device for protein drugs. In vitro drug release showed that chitosan microneedles
      can provide a sustained release of BSA for at least 8 days (approximately 95% of
      drugs released in 8 days). When the Alexa Fluor 488-labeled BSA (Alexa 488-BSA)
      loaded microneedles were applied to the rat skin in vivo, confocal microscopic
      images showed that BSA can gradually diffuse from the puncture sites to the
      dermal layer and the fluorescence of Alexa 488-BSA can be observed at the depth
      of 300 MUm. In addition, encapsulation of BSA within the microneedle matrix did
      not alter the secondary structure of BSA, indicating that the gentle nature of
      the fabrication process allowed for encapsulation of fragile biomolecules. These
      results suggested that the developed chitosan microneedles may serve as a
      promising device for transdermal delivery of macromolecules in a sustained
      manner.

PMID- 23116142
TI  - Characterization of apigenin and luteolin derivatives from oil palm (Elaeis
      guineensis Jacq.) leaf using LC-ESI-MS/MS.
AB  - The palm oil industry generates several byproducts, and more than half of the dry
      weight of the waste is of oil palm leaf whereby the tissue is underutilized.
      Recently, several research studies found promising potential of oil palm fronds
      as a source of nutraceutical due to its bioactive properties. However, the
      chemical composition of the tissue is still not deciphered. Using reversed-phase
      liquid chromatography (LC) electrospray mass spectrometry (ESI-MS), glycosylated
      apigenin and luteolin were separated and identified from oil palm (Elaeis
      guineensis Jacq.) leaf and structures of the constituents were elucidated by
      collision-induced dissociation (CID) tandem MS. From 28 derivatives of the
      flavones, 9 compounds were conjugated with hydroxymethylglutaric (HMG) acid.
      Improved knowledge on oil palm especially on bioactive component of the leaf
      tissue will allow correlation of its beneficial effects and further promotes
      efficient utilization of this agriculture byproduct.

PMID- 23116141
TI  - Side-chain dynamics reveals transient association of Abeta(1-40) monomers with
      amyloid fibers.
AB  - Low-lying excited states that correspond to rare conformations or transiently
      bound species have been hypothesized to play an important role for amyloid
      nucleation. Despite their hypothesized importance in amyloid formation,
      transiently occupied states have proved difficult to detect directly. To
      experimentally characterize these invisible states, we performed a series of Carr
      Purcell-Meiboom-Gill (CPMG)-based relaxation dispersion NMR experiments for the
      amyloidogenic Abeta(1-40) peptide implicated in Alzheimer's disease. Significant
      relaxation dispersion of the resonances corresponding to the side-chain amides of
      Q15 and N27 was detected before the onset of aggregation. The resonances
      corresponding to the peptide backbone did not show detectable relaxation
      dispersion, suggesting an exchange rate that is not within the practical limit of
      detection. This finding is consistent with the proposed "dock and lock" mechanism
      based on molecular dynamics simulations in which the Abeta(1-40) monomer
      transiently binds to the Abeta(1-40) oligomer by non-native contacts with the
      side chains before being incorporated into the fiber through native contacts with
      the peptide backbone.

PMID- 23116143
TI  - Recent advances in the rationale design of GPER ligands.
AB  - G-Protein Coupled Receptor (GPCR) superfamily, which comprises approximately 900
      members, is the largest family of protein targets with proven therapeutic value.
      Although at least 500 GPCRs have been identified as therapeutically relevant,
      only thirteen GPCRs have been structurally characterized in apo-form or in
      complex with ligands. GPCRs share relatively low sequence similarity making hard
      the process of homology modelling, nevertheless some successful hits have been
      determined. Recently, the G-protein-coupled estrogen receptor 1 (GPER, formerly
      known as GPR30) has attracted increasing interest due to its ability in mediating
      estrogen signaling in different normal and cancer tissues. In this regard, the
      identification of selective GPER ligands has provided valuable tools in order to
      differentiate the specific functions elicited by this novel estrogen receptor
      respect to those exerted by the classical estrogen receptors (ERs). In this
      review, we focus on GPER examining "in silico" docking simulations and evaluating
      the different binding modes of diverse natural and synthetic ligands.

PMID- 23116144
TI  - Multivalent agents: a novel concept and preliminary practice in Anti-HIV drug
      discovery.
AB  - The term multivalency (polyvalency) in the biological science is defined as the
      simultaneous binding of multiple ligands to one receptor (or multiple receptors
      to one ligand). The possibility of gaining potency and selectivity was
      significantly increased through the use of multivalent ligand as a homo- or
      hetero-dimer, thus multivalent ligands provided a more attractive strategy to
      design novel anti-HIV agents with therapeutic applications. Moreover, similar to
      phenomenon of multivalency, an alternative strategy is called the "mixed sites
      inhibitor", viz. a single molecule that possesses enough chemical space to
      maximize interactions with its complementary binding pocket, or to bind
      simultaneously in more than one regions in a target. Actually, the addition of a
      third heterocyclic nucleus to the parent compound resulted in "mixed sites" anti
      HIV agents with broad spectrum of activities against the mutant HIV-1 strains.
      Based on current representative examples, the present article provided a brief
      review on the rationale for the design of different classes of multivalency anti
      HIV agents and also discussed the advantages over their monomeric counterparts,
      providing a novel paradigm to facilitate the development of anti-HIV/AIDS
      therapeutic agents in treatment of HIV infected community.

PMID- 23116145
TI  - A cyclometallated iridium(III) complex as a c-myc G-quadruplex stabilizer and
      down-regulator of c-myc oncogene expression.
AB  - A new cyclometallated iridium(III) complex with the 2,2'-biquinoline N-donor
      ligand has been synthesized and characterized. The interaction and affinity of
      the complex towards c-myc G-quadruplex and duplex DNA have been investigated
      using UV/Vis spectroscopy and gel mobility shift assay. These studies revealed
      that complex 1 binds to c-myc G-quadruplexes (Pu22 and Pu27) with high affinity
      but does not interact with duplex DNA either by intercalation or groove binding.
      The ability of 1 to stabilize c-myc G-quadruplex DNA in vitro has also been
      examined through a PCR stop assay and a cell-based luciferase reporter assay.
      Complex 1 displays promising cytotoxic activity against the HeLa cell line with
      sub-micromolar potency.

PMID- 23116146
TI  - Vancomycin-resistant enterococci in rooks (Corvus frugilegus) wintering
      throughout Europe.
AB  - This study's aims were to assess the prevalence of, and to characterize,
      vancomycin-resistant enterococci (VRE) from rooks (Corvus frugilegus) wintering
      in Europe during 2010/2011. Faeces samples were cultivated selectively for VRE
      and characterized. Pulsed-field gel electrophoresis and multilocus sequence
      typing (MLST) were used to examine epidemiologic relationships of vanA-containing
      VRE. The vanA-carrying VRE were tested in vitro for mobility of vancomycin
      resistance traits. VRE were found in 62 (6%) of 1073 rook samples. Enterococcal
      species diversity comprised Enterococcus gallinarum (48 isolates), followed by E.
      faecium (9) and E. faecalis (5). Eight VRE harboured the vanA and ermB genes.
      Seven vanA-carrying VRE originated from the Czech Republic and one from Germany.
      All vanA-carrying VRE were identified as E. faecium. Based on MLST analysis, six
      vanA-positive isolates were grouped as ST92 type, one isolate belonged to ST121,
      and the remaining one was described as a novel type ST671. Seven out of eight
      isolates were able to transfer the vancomycin resistance trait via filter mating
      with a transfer rate of 8.95 +/- 3.25 * 10(-7)  transconjugants per donor. In
      conclusion, wintering rooks in some European countries may disseminate clinically
      important enterococci and pose a risk for environmental contamination.

PMID- 23116147
TI  - Rapid discovery of highly potent and selective inhibitors of histone deacetylase
      8 using click chemistry to generate candidate libraries.
AB  - To find HDAC8-selective inhibitors, we designed a library of HDAC inhibitor
      candidates, each containing a zinc-binding group that coordinates with the active
      site zinc ion, linked via a triazole moiety to a capping structure that interacts
      with residues on the rim of the active site. These compounds were synthesized by
      using click chemistry. Screening identified HDAC8-selective inhibitors including
      C149 (IC(50) = 0.070 MUM), which was more potent than PCI-34058 (6) (IC(50) =
      0.31 MUM), a known HDAC8 inhibitor. Molecular modeling suggested that the
      phenylthiomethyl group of C149 binds to a unique hydrophobic pocket of HDAC8, and
      the orientation of the phenylthiomethyl and hydroxamate moieties (fixed by the
      triazole moiety) is important for the potency and selectivity. The inhibitors
      caused selective acetylation of cohesin in cells and exerted growth-inhibitory
      effects on T-cell lymphoma and neuroblastoma cells (GI(50) = 3-80 MUM). These
      findings suggest that HDAC8-selective inhibitors have potential as anticancer
      agents.

PMID- 23116148
TI  - Irrational use of antimalarial drugs in rural areas of eastern Pakistan: a random
      field study.
AB  - BACKGROUND: Prescription of antimalarial drugs in the absence of malarial disease
      is a common practice in countries where malaria is endemic. However, unwarranted
      use of such drugs can cause side effects in some people and is a financial drain
      on local economies. In this study, we surveyed the prevalence of malaria
      parasites in humans, and the prevalence of the malaria transmitting mosquito
      vectors in the study area. We also investigated the use of antimalarial drugs in
      the local people. We focused on randomly selected rural areas of eastern Pakistan
      where no malaria cases had been reported since May 2004. METHODS: Mass blood
      surveys, active case detection, passive case detection, and vector density
      surveys were carried out in selected areas of Sargodha district from September
      2008 to August 2009. Data pertaining to the quantities and types of antimalarial
      drugs used in these areas were collected from health centers, pharmacies, and the
      district CDC program of the Health Department of the Government of the Punjab.
      RESULTS: Seven hundred and forty four blood samples were examined, resulting in a
      Blood Examination Rate (BER) of 3.18; microscopic analysis of blood smears showed
      that none of the samples were positive for malaria parasites. Investigation of
      the mosquito vector density in 43 living rooms (bedrooms or rooms used for
      sleeping), 23 stores, and 32 animal sheds, revealed no vectors capable of
      transmitting malaria in these locations. In contrast, the density of Culex
      mosquitoes was high. Substantial consumption of a variety of antimalarial
      tablets, syrups, capsules and injections costing around 1000 US$, was documented
      for the region. CONCLUSION: Use of antimalarial drugs in the absence of malarial
      infection or the vectors that transmit the disease was common in the study area.
      Continuous use of such drugs, not only in Pakistan, but in other parts of the
      world, may lead to drug-induced side effects amongst users. Better training of
      health care professionals is needed to ensure accurate diagnoses of malaria and
      appropriate prescription of antimalarial drugs delivered to communities.

PMID- 23116149
TI  - Identification of autoantibodies expressed in acquired aplastic anaemia.
AB  - Acquired aplastic anaemia (aAA) is recognized as an autoimmune disorder; however,
      the autoantigens and target cells involved remain elusive. Expression of
      autoantibodies and their target cells were examined using the haematopoietic cell
      line K562 and bone marrow stromal cell line hTS-5; 43.5% and 21.7% of aAA
      expressed autoantibody against K562 and hTS-5 cells, respectively. The
      autoantigens were identified by serological identification of antigens through
      recombinant cDNA expression cloning. This study indicates that haematopoietic
      cells are the targets of immune abnormality in aAA. These autoantibodies may be
      utilized to distinguish patients associated with immune abnormality from bone
      marrow failure syndrome.

PMID- 23116151
TI  - Somatic mutation of H3F3A, a chromatin remodeling gene, is rare in acute
      leukemias and non-Hodgkin lymphoma.

PMID- 23116150
TI  - Effect of aqueous extract and fractions of Zhi-Zi-Hou-Pu decoction against
      depression in inescapable stressed mice: Restoration of monoamine
      neurotransmitters in discrete brain regions.
AB  - CONTEXT: Zhi-Zi-Hou-Pu decoction (ZZHPD) is a traditional prescription which has
      been used to treat "Yu-syndrome" (depression and melancholia) in Chinese herbal
      medication. OBJECTIVE: To evaluate antidepressant activities of ZZHPD, its
      fractions and possible mechanism(s) of action. MATERIALS AND METHODS: ZZHPD
      (1241, 2482 and 4964 mg/kg), n-butanol fraction (ZH-BA, 1454 mg/kg), cyclohexane
      fraction (ZH-CH, 17 mg/kg) and aqueous fraction (ZH-AQ, 3493 mg/kg) were
      administered orally to different groups of mice for seven consecutive days.
      Forced Swimming Test (FST) and Tail Suspension Test (TST) were conducted 60 min
      after the last administration to evaluate the antidepressant effect.
      Norepinephrine, dopamine and 5-hydroxytryptamine levels in discrete brain parts
      were determined by HPLC-FD immediately after behavioral tests. RESULTS: ZZHPD at
      2482, 4964 mg/kg, ZH-BA (1454 mg/kg), ZH-CH (17 mg/kg) or clomipramine
      hydrochloride (20 mg/kg) significantly (p < 0.05) reduced the duration of
      immobility in FST and TST without affecting locomotor activities in the open
      field test. Observed from score plot of principle component analysis of monoamine
      levels in different groups, the monoamine profile of ZZHPD-treated mice were
      similar to that of the normal control mice. HPLC-UV analysis indicated that
      iridoid glycosides, flavones and neolignans might be the active chemicals.
      DISCUSSION AND CONCLUSION: The results demonstrated significant antidepressant
      like effect of ZZHPD in mice which was related to monoaminergic system, ZH-BA and
      ZH-CH could be the active fractions responsible for the antidepressant effect of
      ZZHPD.

PMID- 23116152
TI  - Evaluation of the metastatic status of lymph nodes identified using axillary
      reverse mapping in breast cancer patients.
AB  - BACKGROUND: Axillary reverse mapping (ARM) is a new technique to preserve upper
      extremity lymphatic pathways during axillary lymph node dissection (ALND),
      thereby preventing lymphedema patients with breast cancer. However, the oncologic
      safety of sparing the nodes identified by ARM (ARM nodes), some of which are
      positive, has not been verified. We evaluated the metastatic status of ARM nodes
      and the efficacy of fine needle aspiration cytology (FNAC) in assessing ARM node
      metastasis. METHODS: Sixty patients with breast cancer who underwent ARM during
      ALND between January 2010 and July 2012 were included in this study. Twenty-five
      patients were clinically node-positive and underwent ALND without sentinel lymph
      node biopsy (SLNB). Thirty-five patients were clinically node-negative but
      sentinel node-positive on the SLND. The lymphatic pathway was visualized using
      fluorescence imaging with indocyanine green. ARM nodes in ALND field, whose
      status was diagnosed using FNAC, were removed and processed for histology. We
      evaluated the correlation between the cytological findings of FNAC and the
      histological analysis of excised ARM nodes. RESULTS: The mean number of ARM nodes
      identified per patient was 1.6 +/-0.9 in both groups. In most patients without
      (88%) and with (79%) SLNB, the ARM nodes were located between the axillary vein
      and the second intercostobrachial nerve. FNAC was performed for 45 ARM nodes, 10
      of which could not be diagnosed. Six of the patients without SLNB (24%) and
      onewith SLNB (3%) had positive ARM nodes. Of these sevenpatients, four had >3
      positive ARM nodes. There was no discordance between the cytological and
      histological diagnosis of ARM nodes status. CONCLUSIONS: Positive ARM nodes were
      observed in the patients not only with extensive nodal metastasis but also in
      those with a few positive nodes. FNAC for ARM nodes was helpful in assessing ARM
      nodes metastasis, which can be beneficial in sparing nodes essential for
      lymphatic drainage, thereby potentially reducing the incidence of lymphedema.
      However, the success of sampling rates needs to be improved.

PMID- 23116153
TI  - Toward understanding the genetic basis of adaptation to high-elevation life in
      poikilothermic species: a comparative transcriptomic analysis of two ranid frogs,
      Rana chensinensis and R. kukunoris.
AB  - BACKGROUND: Understanding how organisms adapt to high-elevation environments at a
      genome scale provides novel insights into the process of adaptive evolution.
      Previous studies have mainly focused on endothermic organisms, while
      poikilothermic species may have evolved different mechanisms to cope with high
      elevation environments. In this context, we sequenced transcriptomes of a pair of
      closely related anuran species, Rana chensinensis and R. kukunoris, which inhabit
      respective low- and high-elevation habitats. By comparing the two transcriptomes,
      we identified candidate genes that may be involved in high-elevation adaption in
      poikilothermic species. RESULTS: Over 66 million sequence reads from each
      transcriptome were generated. A total of 41,858 and 39,293 transcripts for each
      species were obtained by de novo assembly. By comparing the orthologous
      transcripts, we identified 125 protein-coding genes that have likely experienced
      strong positive selection (Ka/Ks>1). In addition, 335 genes that may bear a
      signature of positive selection (1>=Ka/Ks>0.5) were also recognized. By
      considering their functions, fourteen candidate genes were determined to be
      likely involved in high-elevation adaptation, including two CYP genes, USP-1, and
      several others. CONCLUSIONS: We identified a set of candidate genes that may have
      promoted adaptation of R. kukunoris to its high-elevation environment. These
      include several genes that have previously been associated with oxygen binding,
      response to UV radiation, and repair of free radical injury. Detailed molecular,
      physiological, and phenotypic studies are required to better understand the roles
      of these genes in improving the performance of R. kukunoris in a high-elevation
      environment. We have evidence for both convergent and divergent evolution between
      endothermic and poikilothemic species, but additional research across a wide
      range of organisms will be necessary to comprehend the complexity of high
      elevation adaptation.

PMID- 23116154
TI  - Identification and characterization of the Populus AREB/ABF subfamily.
AB  - Abscisic acid (ABA) is a major plant hormone that plays an important role in
      responses to abiotic stresses. The ABA-responsive element binding protein/ABRE
      binding factor (AREB/ABF) gene subfamily contains crucial transcription factors
      in the ABA-mediated signaling pathway. In this study, a total of 14 putative
      AREB/ABF members were identified in the Populus trichocarpa Torr. & Gray. genome
      using five AREB/ABF amino acid sequences from Arabidopsis thaliana L. as probes.
      The 14 putative Populus subfamily members showed high protein similarities,
      especially in the basic leucine zipper (bZIP) domain region. A neighbor-joining
      analysis combined with gene structure data revealed homology among the 14 genes.
      The expression patterns of the Populus AREB/ABF subfamily suggested that the most
      abundant transcripts of 11 genes occurred in leaf tissues, while two genes were
      most transcribed in root tissues. Significantly, eight Populus AREB/ABF gene
      members were upregulated after treatment with 100 MUM exogenous ABA, while the
      other six members were downregulated. We identified the expression profiles of
      the subfamily members in Populus tissues and elucidated different response
      patterns of Populus AREB/ABF members to ABA stress. This study provided insight
      into the roles of Populus AREB/ABF homologues in plant response to abiotic
      stresses.

PMID- 23116155
TI  - Noninnocent role of N-methyl pyrrolidinone in thiazolidinethione-promoted
      asymmetric aldol reactions.
AB  - The origin of stereoselectivity in the reaction between alpha-azido titanium
      enolate derived from chiral auxiliary N-acyl thiazolidinethione and benzaldehyde
      is established using the DFT(B3LYP) method. A nonchelated transition state with N
      methyl-2-pyrrolidinone (NMP) bound to a TiCl(3) enolate is found to be
      energetically the most preferred model responsible for the formation of an Evans
      syn aldol product. The TS model devoid of NMP, although of higher energy, is
      found to be successful in predicting the right stereochemical outcome.

PMID- 23116156
TI  - Endoscopic management of anastomotic leakage after gastrectomy for gastric
      cancer: how efficacious is it?
AB  - BACKGROUND: Anastomotic leak is a dreadful complication with a high mortality
      rate. The authors aimed to evaluate the efficacy of endoscopic closure of
      anastomotic dehiscence after gastrectomy in patients with gastric cancer.
      METHODS: The authors retrospectively reviewed 33 patients with anastomotic
      leakage who had underdone endoscopic treatment among 5249 patients with gastric
      cancer who underwent radical total or subtotal gastrectomy. Methods of endoscopic
      closure included clipping with or without detachable snare, fibrosealant,
      Histoacryl(r) or stent insertion. Results of endoscopic treatment were
      categorized as complete, partial closure and failure. RESULTS: The size of the
      tissue defect was the only factor that had statistically significant differences
      among the cases with complete closure, partial closure and failure (p = 0.005).
      For tissue defects smaller than 2 cm in size, complete closure was achieved in 19
      (73.1%), partial closure in 5 patients (19.2%) and 2 failed (7.6%). For those
      larger than 2 cm in size, one (14.3%) was completely closed, four (57.1%) were
      partially closed and two (28.6%) failed. CONCLUSIONS: Endoscopic treatment for
      anastomotic dehiscence smaller than 2 cm in size had excellent success rate in
      this study.

PMID- 23116157
TI  - Post-translational modification in the archaea: structural characterization of
      multi-enzyme complex lipoylation.
AB  - Lipoylation, the covalent attachment of lipoic acid to 2-oxoacid dehydrogenase
      multi-enzyme complexes, is essential for metabolism in aerobic bacteria and
      eukarya. In Escherichia coli, lipoylation is catalysed by LplA (lipoate protein
      ligase) or by LipA (lipoic acid synthetase) and LipB [lipoyl(octanoyl)
      transferase] combined. Whereas bacterial and eukaryotic LplAs comprise a single
      two-domain protein, archaeal LplA function typically involves two proteins, LplA
      N and LplA-C. In the thermophilic archaeon Thermoplasma acidophilum, LplA-N and
      LplA-C are encoded by overlapping genes in inverted orientation (lpla-c is
      upstream of lpla-n). The T. acidophilum LplA-N structure is known, but the LplA-C
      structure is unknown and LplA-C's role in lipoylation is unclear. In the present
      study, we have determined the structures of the substrate-free LplA-N-LplA-C
      complex and E2lipD (dihydrolipoyl acyltransferase lipoyl domain) that is
      lipoylated by LplA-N-LplA-C, and carried out biochemical analyses of this
      archaeal lipoylation system. Our data reveal the following: (i) LplA-C is
      disordered but folds upon association with LplA-N; (ii) LplA-C induces a
      conformational change in LplA-N involving substantial shortening of a loop that
      could repress catalytic activity of isolated LplA-N; (iii) the adenylate-binding
      region of LplA-N-LplA-C includes two helices rather than the purely loop
      structure of varying order observed in other LplA structures; (iv) LplAN-LplA-C
      and E2lipD do not interact in the absence of substrate; (v) LplA-N-LplA-C
      undergoes a conformational change (the details of which are currently
      undetermined) during lipoylation; and (vi) LplA-N-LplA-C can utilize octanoic
      acid as well as lipoic acid as substrate. The elucidated functional inter
      dependence of LplA-N and LplA-C is consistent with their evolutionary co
      retention in archaeal genomes.

PMID- 23116160
TI  - Molecular redox: revisiting the electronic structures of the group 9
      metallocorroles.
AB  - The electronic structures of monocationic tris[(5,10,15-pentafluorophenyl)
      corrolato]iridium compounds, [Ir(tpfc)L2](+), where L = 4-cyanopyridine [1](+),
      pyridine [2](+), 4-methoxypyridine [3](+), or 4-(N,N'-dimethylamino)pyridine
      [4](+), have been probed by electron paramagnetic resonance (EPR) spectroscopy,
      Ir L3,2-edge X-ray absorption spectroscopy (XAS), UV/visible (UV-vis)
      spectroelectrochemistry, and density functional theoretical (DFT) calculations.
      The data demonstrate that these complexes, which have been previously formulated
      as either of the limiting cases [Ir(III)(tpfc(*))L2](+) or [Ir(IV)(tpfc)L2](+),
      are best described as possessing a singly occupied molecular orbital (SOMO)
      dominated by tpfc with small but significant Ir admixture. EPR g-values and
      electronic absorption spectra are reproduced well using a simple DFT approach.
      These quantities depend profoundly upon Ir orbital contribution to the SOMO. To
      wit, the calculated Ir spin population ranges from 10.6% for [1](+) to 16.3% for
      [4](+), reflecting increased Ir d mixing into the SOMO with increasingly electron
      rich axial ligation. This gives rise to experimentally measured gz values ranging
      from 2.335 to 2.533, metal-to-ligand charge transfer (MLCT) bands ranging from
      14730 and 14330 cm(-1), and [Ir(tpfc)L2](+/0) reduction potentials ranging from
      0.305 to 0.035 V vs Fc(+/0). In addition, the calculated Ir character in the SOMO
      tracks with estimated Ir L3,2 XAS branching ratios (EBR), reflecting the
      increasing degree of Ir d orbital character upon proceeding from [1](+) to
      [4](+). 

PMID- 23116158
TI  - Brain region-specific altered expression and association of mitochondria-related
      genes in autism.
AB  - BACKGROUND: Mitochondrial dysfunction (MtD) has been observed in approximately
      five percent of children with autism spectrum disorders (ASD). MtD could impair
      highly energy-dependent processes such as neurodevelopment, thereby contributing
      to autism. Most of the previous studies of MtD in autism have been restricted to
      the biomarkers of energy metabolism, while most of the genetic studies have been
      based on mutations in the mitochondrial DNA (mtDNA). Despite the mtDNA, most of
      the proteins essential for mitochondrial replication and function are encoded by
      the genomic DNA; so far, there have been very few studies of those genes.
      Therefore, we carried out a detailed study involving gene expression and genetic
      association studies of genes related to diverse mitochondrial functions. METHODS:
      For gene expression analysis, postmortem brain tissues (anterior cingulate gyrus
      (ACG), motor cortex (MC) and thalamus (THL)) from autism patients (n=8) and
      controls (n=10) were obtained from the Autism Tissue Program (Princeton, NJ,
      USA). Quantitative real-time PCR arrays were used to quantify the expression of
      84 genes related to diverse functions of mitochondria, including biogenesis,
      transport, translocation and apoptosis. We used the delta delta Ct (??Ct) method
      for quantification of gene expression. DNA samples from 841 Caucasian and 188
      Japanese families were used in the association study of genes selected from the
      gene expression analysis. FBAT was used to examine genetic association with
      autism. RESULTS: Several genes showed brain region-specific expression
      alterations in autism patients compared to controls. Metaxin 2 (MTX2),
      neurofilament, light polypeptide (NEFL) and solute carrier family 25, member 27
      (SLC25A27) showed consistently reduced expression in the ACG, MC and THL of
      autism patients. NEFL (P = 0.038; Z-score 2.066) and SLC25A27 (P = 0.046; Z-score
      1.990) showed genetic association with autism in Caucasian and Japanese samples,
      respectively. The expression of DNAJC19, DNM1L, LRPPRC, SLC25A12, SLC25A14,
      SLC25A24 and TOMM20 were reduced in at least two of the brain regions of autism
      patients. CONCLUSIONS: Our study, though preliminary, brings to light some new
      genes associated with MtD in autism. If MtD is detected in early stages,
      treatment strategies aimed at reducing its impact may be adopted.

PMID- 23116159
TI  - Ligand-enabled methylene C(sp3)-H bond activation with a Pd(II) catalyst.
AB  - Pd(II) insertion into beta-methylene C(sp(3))-H bonds was enabled by a mutually
      repulsive and electron-rich quinoline ligand. Ligand tuning led to the
      development of a method that allows for installation of an aryl group on a range
      of acyclic and cyclic amides containing beta-methylene C(sp(3))-H bonds.

PMID- 23116161
TI  - Functional foods and the biomedicalisation of everyday life: a case of germinated
      brown rice.
AB  - Germinated brown rice (GBR) is a functional food, whose benefits for chronic
      diseases have been demonstrated by scientific research on a single constituent of
      GBR, gamma aminobutyric acid. This article examines the processes through which
      the emphasis on biomedical rationality made during the production and consumption
      of functional foods is embedded in the complicated social contexts of the post
      1990s. In the case of GBR, the Korean government, food scientists, mass media and
      consumers have added cultural accounts to the biomedical understanding of foods.
      In particular, consumers have transformed their households and online communities
      into a place for surveillance medicine. Functional foods are embedded in multiple
      actors' perspectives on what healthy foods mean and how and where the risks of
      chronic diseases should be managed. 

PMID- 23116163
TI  - Nanoparticle assembly on topographical polymer templates: effects of spin rate,
      nanoparticle size, ligand, and concentration.
AB  - The ability to assemble nanoparticles (NPs) into desired patterns in a controlled
      fashion is crucial for the study of collective properties and for the fabrication
      of a variety of NP-based devices. Drying-mediated assembly directed by a template
      provides a facile route for organizing NPs in predefined patterns. We utilize the
      branched topographical landscapes displayed by partially crystallized
      poly(ethylene glycol) (PEG) films as a generic template for studying the drying
      mediated organization of dodecanethiol- and polystyrene thiol-protected gold NPs
      (Au-DT and Au-PS), and explore the combined effects of NP size and ligand,
      concentration, and spin rate on the distribution of NPs inside the channels. We
      show how NP concentration and the spin rate applied during NP deposition can be
      used to influence the tendency of NPs either to fill the channel uniformly or to
      localize near the channel edges, explain the important role of the enhanced
      aggregation tendency of larger NPs on the resulting morphologies, and demonstrate
      how this tendency can be tuned by the proper choice of ligands. The different
      effects are explained in the context of possible scenarios of drying-mediated
      assembly by analyzing the relevant interactions and forces acting on the NPs
      during solvent evaporation.

PMID- 23116162
TI  - Platelet-derived growth factor induced alpha-smooth muscle actin expression by
      human retinal pigment epithelium cell.
AB  - PURPOSES: (1) To evaluate the association between expression of alpha-smooth
      muscle actin (alpha-SMA) in proliferative vitreoretinopathy (PVR) and the
      pathological grading of PVR, and the effect of platelet-derived growth factor
      (PDGF) on the expression of alpha-SMA by human retinal pigment epithelial (RPE)
      cells. (2) To investigate the potential induction of PDGF on the proliferation
      and migration of human RPE cells as well as the signaling pathways responsible.
      METHODS: We immunohistochemically investigated the expression of alpha-SMA in
      PVR. To further investigate the effect of PDGF and the downstream signaling,
      exogenous PDGF-BB and signaling inhibitors were added to cultured human RPE
      cells. The MTT method was performed to detected cell proliferation, while cell
      migration was also measured. RESULTS: alpha-SMA expression was positively
      correlated with the pathological grading of PVR. PDGF-BB could stimulate the
      proliferation and migration of cultured RPE cells through the participation of
      mitogen-activated protein kinase. In addition, PDGF induced alpha-SMA expression.
      The promotion of proliferate/migration and alpha-SMA expression by PDGF-BB was
      enhanced by the presence of serum. CONCLUSIONS: PDGF and alpha-SMA are 2
      potential therapeutic targets for the treatment of PVR.

PMID- 23116164
TI  - The bifunctional role of aconitase in Streptomyces viridochromogenes Tu494.
AB  - In many organisms, aconitases have dual functions; they serve as enzymes in the
      tricarboxylic acid cycle and as regulators of iron metabolism. In this study we
      defined the role of the aconitase AcnA in Streptomyces viridochromogenes Tu494,
      the producer of the herbicide phosphinothricyl-alanyl-alanine, also known as
      phosphinothricin tripeptide or bialaphos. A mutant in which the aconitase gene
      acnA was disrupted showed severe defects in morphology and physiology, as it was
      unable to form any aerial mycelium, spores nor phosphinothricin tripeptide. AcnA
      belongs to the iron regulatory proteins (IRPs). In addition to its catalytic
      function, AcnA plays a regulatory role by binding to iron responsive elements
      (IREs) located on the untranslated region of certain mRNAs. A mutation preventing
      the formation of the [4Fe-4S] cluster of AcnA eliminated its catalytic activity,
      but did not inhibit RNA-binding ability. In silico analysis of the S.
      viridochromogenes genome revealed several IRE-like structures. One structure is
      located upstream of recA, which is involved in the bacterial SOS response, and
      another one was identified upstream of ftsZ, which is required for the onset of
      sporulation in streptomycetes. The functionality of different IRE structures was
      proven with gel shift assays and specific IRE consensus sequences were defined.
      Furthermore, RecA was shown to be upregulated on post-transcriptional level under
      oxidative stress conditions in the wild-type strain but not in the acnA mutant,
      suggesting a regulatory role of AcnA in oxidative stress response.

PMID- 23116165
TI  - In situ molecular-level insights into the interfacial structure changes of
      membrane-associated prion protein fragment [118-135] investigated by sum
      frequency generation vibrational spectroscopy.
AB  - Protein aggregation is associated with many "protein deposition diseases". A
      precise molecular detail of the conformational transitions of such a membrane
      associated protein structure is critical to understand the disease mechanism and
      develop effective treatments. One potential model peptide for studying the
      mechanism of protein deposition diseases is prion protein fragment [118-135]
      (PrP118-135), which shares homology with the C-terminal domain of the Alzheimer's
      beta-amyloid peptide. In this study, sum frequency generation vibrational
      spectroscopy (SFG-VS) has been applied to characterize interactions between
      PrP118-135 and 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (POPG)
      lipid bilayer in situ. The conformation change and orientation of PrP118-135 in
      lipid bilayers have been determined using SFG spectra with different polarization
      combinations. It is found that low-concentration PrP118-135 predominantly adopts
      alpha-helical structure but with tiny beta-sheet structure. With the PrP118-135
      concentration increasing, the molecular number ratio of parallel beta-sheet
      structure increases and reaches about 44% at a concentration of 0.10 mg/mL,
      indicating the formation of abnormally folded scrapie isoforms. The alpha-helical
      structure inserts into the lipid bilayer with a tilt angle of ~32 degrees  versus
      the surface normal, while the beta-sheet structure lies down on the lipid bilayer
      with the tilt and twist angle both of 90 degrees . The 3300 cm(-1) N-H stretching
      signal in psp spectra arises from alpha-helical structure at low PrP
      concentration and from the beta-sheet structure at high PrP concentration.
      Results from this study will provide an in-depth insight into the early events in
      the aggregation of PrP in cell membrane.

PMID- 23116166
TI  - Cortisol regulation in 12-month-old human infants: associations with the infants'
      early history of breastfeeding and co-sleeping.
AB  - Experiences during early life are suggested to affect the physiological systems
      underlying stress responses, including the hypothalamic-pituitary-adrenal axis
      (HPA axis). While stressful early experiences have been associated with
      dysregulated HPA-axis functioning, positive early experiences, i.e. high maternal
      caregiving quality, contribute to more optimal HPA-axis functioning. Influences
      of other early caregiving factors, however, are less well documented. The goal of
      this study was to examine whether breastfeeding and co-sleeping during the first
      6 months of life were associated with infant cortisol regulation, i.e. cortisol
      reactivity and recovery, to a stressor at 12 months of age. Participants were 193
      infants and their mothers. Information on breastfeeding and co-sleeping was
      collected using weekly and daily sleep diaries, respectively, for the first 6
      months of life. Co-sleeping was defined as sleeping in the parents' bed or
      sleeping in the parents' room. At 12 months of age, infants were subjected to a
      psychological stressor [Strange Situation Procedure (SSP); Ainsworth et al.
      1978]. Salivary cortisol was measured prestressor and at 25, 40, and 60 min
      poststressor to measure reactivity and recovery. Regression analyses showed that
      after controlling for maternal sensitivity, infant attachment status, feeding,
      and sleeping arrangements at 12 months of age and other confounders, more weeks
      of co-sleeping predicted lower infant cortisol reactivity to the SSP. Also, more
      weeks of breastfeeding predicted quicker cortisol recovery. These results
      indicate that an early history of co-sleeping and breastfeeding contributes
      positively to cortisol regulation in 12-month-olds.

PMID- 23116167
TI  - Barbers' knowledge and practice about occupational biological hazards was low in
      Gondar town, North West Ethiopia.
AB  - BACKGROUND: Several health hazards including communicable diseases and skin
      conditions are associated with Barbers' profession to which their visitors are
      exposed. Thus, knowledge and practice of Barbers would play a vital part in
      prevention and control of these health hazards. So, the aim of this study is to
      assess knowledge and practice, and associated factors among barbers about
      biological hazards associated with their profession in Gondar town, North West
      Ethiopia. METHODS: To assess knowledge and practice, and associated factors among
      barbers about biological hazards associated with their profession in Gondar town,
      North West Ethiopia, A work place based cross-sectional study was conducted from
      March 28 to April 6, 2012. The total numbers of Barbers in the town were 960 of
      which 400 Barbers were participated in the study. Sample size was determined
      using the formula for single population proportion by considering, 51%
      proportion, knowledgeable Barbers from Jimma, Ethiopia, 95% level of confidence,
      5% margin of error and 15% none response rate. The numbers of barbers included in
      the study were selected by using systematic random sampling. Data was collected
      by face to face interview using a structured and pre-tested questionnaire. Binary
      and multivariate logistic regression analyses were conducted to identify factors
      associated with knowledge and practice of barbers. RESULTS: Of 400 barbers, only
      72 (18%) had good knowledge about biological hazards associated to their
      profession, While only 61 (15.3%) were practicing safely during barbering.
      Knowledge of the barbers was associated significantly with educational level,
      owner of the business, working hour and work experience, while practice was
      associated only with availability of UV sterilizers in the room and working hour.
      CONCLUSION: Barbers' practice and knowledge to prevent biological hazards
      associated with their profession is very poor. Thus, giving training for the
      Barbers is required toward prevention of biological hazards associated to their
      profession.

PMID- 23116168
TI  - Structural optimization and structure-activity relationships of N2-(4-(4
      Methylpiperazin-1-yl)phenyl)-N8-phenyl-9H-purine-2,8-diamine derivatives, a new
      class of reversible kinase inhibitors targeting both EGFR-activating and
      resistance mutations.
AB  - This paper describe the structural optimization of a hit compound, N2-(4-(4
      methylpiperazin-1-yl)phenyl)-N8-phenyl-9H-purine-2,8-diamine (1), which is a
      reversible kinase inhibitor targeting both EGFR-activating and drug-resistance
      (T790M) mutations but has poor binding affinity. Structure-activity relationship
      studies led to the identification of 9-cyclopentyl-N2-(4-(4-methylpiperazin-1
      yl)phenyl)-N8-phenyl-9H-purine-2,8-diamine (9e) that exhibits significant in
      vitro antitumor potency against the non-small-cell lung cancer (NSCLC) cell lines
      HCC827 and H1975, which harbor EGFR-activating and drug-resistance mutations,
      respectively. Compound 9e was further assessed for potency and selectivity in
      enzymatic assays and in vivo anti-NSCLC studies. The results indicated that
      compound 9e is a highly potent kinase inhibitor against both EGFR-activating and
      resistance mutations and has good kinase spectrum selectivity across the kinome.
      In vivo, oral administration of compound 9e at a dose of 5 mg/kg caused rapid and
      complete tumor regression in a HCC827 xenograft model, and an oral dose of 50
      mg/kg initiated a considerable antitumor effect in an H1975 xenograft model.

PMID- 23116169
TI  - A neuroimaging pattern-recognition approach in pediatric intracranial
      calcifications.

PMID- 23116170
TI  - The multilevel diagram.

PMID- 23116171
TI  - Synthesis of dispersible ferromagnetic graphene nanoribbon stacks with enhanced
      electrical percolation properties in a magnetic field.
AB  - Iron-intercalated and tetradecyl-edge-functionalized graphene nanoribbon stacks
      (Fe@TD-GNRs) can be made from commercially available carbon nanotubes by a facile
      synthesis. The physical properties of the Fe@TD-GNRs were analyzed by
      transmission electron microscopy, thermogravimetric analysis, X-ray photoelectron
      spectroscopy, evolved gas analysis, Raman spectroscopy, and scanning electron
      microscopy. By the intercalation of iron, the alignment of the Fe@TD-GNRs in a
      magnetic field was enabled. The aligned structures enhanced electrical
      percolation at given concentrations in previously nonconductive solvents.

PMID- 23116173
TI  - Sustainable inhibition efficacy of liposome-encapsulated nisin on insoluble
      glucan-biofilm synthesis by Streptococcus mutans.
AB  - CONTEXT: Dental caries are an infectious oral bacterial disease caused by
      cariogenic streptococci. These streptococci inhabit dental biofilms which
      comprise insoluble glucans. OBJECTIVE: To prevent dental caries, nisin, a
      suitable agent active against Gram-positive bacteria, was examined in vitro for
      its ability to suppress insoluble glucan-biofilm synthesis by cariogenic
      streptococci. MATERIALS AND METHODS: To investigate glucan-biofilm synthesis by a
      typical cariogenic streptococcus, Streptococcus mutans 10449, the naked form of
      nisin was loaded onto a 96-well microplate in vitro model. To prolong the
      efficacy of nisin as a preventive agent, liposome-encapsulated nisin (nisin
      liposome) was examined for its ability to inhibit the synthesis of glucan
      biofilms on microplates. RESULTS: Naked nisin (100 pmol) completely suppressed
      insoluble glucan-biofilm synthesis by S. mutans 10449 following 1 h cultivation
      in 96-well microplates. The concentration of nisin-liposome required for the
      efficacious inhibition of glucan-biofilm synthesis was four times lower than that
      of naked nisin following 2 h cultivation. In particular, nisin-liposome (30 pmol
      nisin equivalent) prolonged the inhibitory activity of nisin against glucan
      biofilm synthesis by S. mutans 10449 for up to 6 h, while naked nisin (30 pmol)
      gradually lost this inhibitory activity over the same period. In vitro release
      assay of nisin from the liposome showed that 76% nisin was released within 6 h.
      DISCUSSION AND CONCLUSION: The findings indicate the usefulness of nisin-liposome
      for the sustained release of nisin. Thus, nisin-liposome could play a potential
      role in preventive medicine as an inhibitor of the glucan-biofilm synthesis.

PMID- 23116172
TI  - DNA methylation profile of Aire-deficient mouse medullary thymic epithelial
      cells.
AB  - BACKGROUND: Medullary thymic epithelial cells (mTECs) are characterized by
      ectopic expression of self-antigens during the establishment of central
      tolerance. The autoimmune regulator (Aire), which is specifically expressed in
      mTECs, is responsible for the expression of a large repertoire of tissue
      restricted antigens (TRAs) and plays a role in the development of mTECs. However,
      Aire-deficient mTECs still express TRAs. Moreover, a subset of mTECs, which are
      considered to be at a stage of terminal differentiation, exists in the Aire
      deficient thymus. The phenotype of a specific cell type in a multicellular
      organism is governed by the epigenetic regulation system. DNA methylation
      modification is an important component of this system. Every cell or tissue type
      displays a DNA methylation profile, consisting of tissue-dependent and
      differentially methylated regions (T-DMRs), and this profile is involved in cell
      type-specific genome usage. The aim of this study was to examine the DNA
      methylation profile of mTECs by using Aire-deficient mTECs as a model. RESULTS:
      We identified the T-DMRs of mTECs (mTEC-T-DMRs) via genome-wide DNA methylation
      analysis of Aire(-/-) mTECs by comparison with the liver, brain, thymus, and
      embryonic stem cells. The hypomethylated mTEC-T-DMRs in Aire(-/-) mTECs were
      associated with mTEC-specific genes, including Aire, CD80, and Trp63, as well as
      other genes involved in the RANK signaling pathway. While these mTEC-T-DMRs were
      also hypomethylated in Aire(+/+) mTECs, they were hypermethylated in control
      thymic stromal cells. We compared the pattern of DNA methylation levels at a
      total of 55 mTEC-T-DMRs and adjacent regions and found that the DNA methylation
      status was similar for Aire(+/+) and Aire(-/-) mTECs but distinct from that of
      athymic cells and tissues. CONCLUSIONS: These results indicate a unique DNA
      methylation profile that is independent of Aire in mTECs. This profile is
      distinct from other cell types in the thymic microenvironment and is indicated to
      be involved in the differentiation of the mTEC lineage.

PMID- 23116174
TI  - Isokinetic rotator muscles fatigue in glenohumeral joint instability before and
      after Latarjet surgery: a pilot prospective study.
AB  - We aimed to analyze the changes in isokinetic internal (IR) and external (ER)
      rotator muscles fatigue (a) in patients with non-operated recurrent anterior
      instability, and (b) before and after shoulder surgical stabilization with the
      Bristow-Latarjet procedure. Thirty-seven patients with non-operated unilateral
      recurrent anterior post-traumatic instability (NG) were compared with 12 healthy
      subjects [control group (CG)]. Twenty patients with operated recurrent anterior
      instability group (OG) underwent isokinetic evaluation before and 3, 6, and 21
      months after Bristow-Latarjet surgery. IR and ER muscles strength was evaluated
      with Con-Trex(r) dynamometer, with subjects seated and at a 45 degrees  shoulder
      abduction angle in scapular plane. IR and ER muscle fatigue was determined after
      10 concentric repetitions at 180 degrees  . s(-1) through the fatigue index, the
      percent decrease in performance (DP), and the slope of peak torque decrease.
      There were no differences in rotator muscles fatigue between NG and CG. In OG, 3
      months post-surgery, IR DP of operated shoulder was significantly (P < 0.001)
      higher than presurgery and 6 and 21 months post-surgery. Rotator muscles
      fatigability was not associated with recurrent anterior instability. After
      surgical stabilization, there was a significantly higher IR fatigability in the
      operated shoulder 3 months post-surgery, followed by recovery evidenced 6 months
      post-surgery and long-term maintenance over 21 months.

PMID- 23116175
TI  - No association between COMT Val158Met polymorphism and prostate cancer risk: a
      meta-analysis.
AB  - OBJECTIVE: Results from published studies on the association between the catechol
      O-methyltransferase (COMT) Val158Met polymorphism and prostate cancer (PCa) risk
      are inconsistent. To derive a more precise estimate, we performed a meta
      analysis. METHODS: We searched in the PubMed and Elsevier Science Direct database
      for studies on the association between the COMT Val158Met polymorphism and PCa.
      We used the odds ratio with 95% confidence interval for PCa risk, detected
      potential sources of heterogeneity with the Chi-square-based Q-test, performed
      sensitivity analysis of studies adapted to the Hardy-Weinberg equilibrium.
      RESULTS: We found seven case-control studies included 2292 patients and 2158
      controls. Fix-effects meta-analysis failed to explore any significant association
      of PCa with the genetic model and the allelic model of COMT Val158Met. We also
      did not detect any association in the subgroup analysis by ethnicity in all
      genetic models. The gene-based analysis suggested that the genetic polymorphism
      in COMT is not associated with PCa. CONCLUSIONS: There is no association between
      the COMT Val158Met polymorphism and PCa.

PMID- 23116176
TI  - Human cytomegalovirus infection inhibits CXCL12- mediated migration and invasion
      of human extravillous cytotrophoblasts.
AB  - BACKGROUND: During the first trimester of pregnancy, a series of tightly
      regulated interactions govern the formation of a highly invasive population of
      fetal-derived extravillous cytotrophoblasts (EVT). Successful pregnancy is
      dependent on efficient invasion of the uterine wall and maternal spiral arteries
      by EVT. Dysregulated trophoblast invasion is associated with intrauterine growth
      restriction, birth defects, spontaneous abortion and preeclampsia. A number of
      soluble growth factors, cytokines, and chemokines modulate this process, fine
      tuning the temporal and spatial aspects of cytotrophoblast invasion. In
      particular, the CXCL12/CXCR4 axis has been shown to specifically modulate
      cytotrophoblast differentiation, invasion, and survival throughout early
      pregnancy. Infection with human cytomegalovirus (HCMV) has been associated with
      impaired differentiation of cytotrophoblasts down the invasive pathway,
      specifically dysregulating the response to mitogens including epidermal growth
      factor (EGF) and hepatocyte growth factor (HGF). In this study, the effect of
      HCMV infection on the CXCL12-mediated migration and invasion of the EVT cell line
      SGHPL-4 was investigated. RESULTS: Infection with HCMV significantly decreased
      secretion of CXCL12 by SGHPL-4 cells, and induced a striking perinuclear
      accumulation of the chemokine. HCMV infection significantly increased mRNA and
      total cell surface expression of the two known receptors for CXCL12: CXCR4 and
      CXCR7. Functionally, HCMV-infected SGHPL-4 cells were unable to migrate or invade
      in response to a gradient of soluble CXCL12 in transwell assays. CONCLUSIONS:
      Collectively, these studies demonstrate that HCMV impairs EVT migration and
      invasion induced by CXCL12. As HCMV has the ability to inhibit EVT migration and
      invasion through dysregulation of other relevant signaling pathways, it is likely
      that the virus affects multiple signaling pathways to impair placentation and
      contribute to some of the placental defects seen in HCMV-positive pregnancies.

PMID- 23116177
TI  - Molecular genetic characterization of a cluster in A. terreus for biosynthesis of
      the meroterpenoid terretonin.
AB  - Meroterpenoids are natural products produced from polyketide and terpenoid
      precursors. A gene targeting system for A. terreus NIH2624 was developed, and a
      gene cluster for terretonin biosynthesis was characterized. The intermediates and
      shunt products were isolated from the mutant strains, and a pathway for
      terretonin biosynthesis is proposed. Analysis of two meroterpenoid pathways
      corresponding to terretonin in A. terreus and austinol in A. nidulans reveals
      that they are closely related evolutionarily.

PMID- 23116178
TI  - An image skeletonization-based tool for pollen tube morphology analysis and
      phenotyping.
AB  - The mechanism underlying pollen tube growth involves diverse genes and molecular
      pathways. Alterations in the regulatory genes or pathways cause phenotypic
      changes reflected by cellular morphology, which can be captured using
      fluorescence microscopy. Determining and classifying pollen tube morphological
      phenotypes in such microscopic images is key to our understanding the involvement
      of genes and pathways. In this context, we propose a computational method to
      extract quantitative morphological features, and demonstrate that these features
      reflect morphological differences relevant to distinguish different defects of
      pollen tube growth. The corresponding software tool furthermore includes a novel
      semi-automated image segmentation approach, allowing to highly accurately
      identify the boundary of a pollen tube in a microscopic image.

PMID- 23116179
TI  - The double-corolla phenotype in the Hawaiian lobelioid genus Clermontia involves
      ectopic expression of PISTILLATA B-function MADS box gene homologs.
AB  - BACKGROUND: The Hawaiian endemic genus Clermontia (Campanulaceae) includes 22
      species, 15 of which, the double-corolla species, are characterized by an extra
      whorl of organs that appear to be true petals occupying what is normally the
      sepal whorl. Previous research has shown that the presence of homeotic petaloid
      organs in some other plant groups correlates with ectopic expression of B
      function MADS box genes, but similar core eudicot examples of apparent groundplan
      divergence remain unstudied. B-function genes, which are not normally expressed
      in the sepal whorl, are required for determination and maintenance of petal
      identity. Here, we investigate the potential role of altered B-function gene
      expression contributing to the morphological diversity of this island genus.
      RESULTS: We examined the morphology and developmental genetics of two different
      species of Clermontia, one of which, C. arborescens, has normal sepals while the
      other, C. parviflora, has two whorls of petal-like organs. Scanning electron
      microscopy of cell surface morphologies of first and second whorl organs in the
      double-corolla species C. parviflora revealed conical epidermal cells on the
      adaxial surfaces of both first and second whorl petaloid organs, strongly
      suggesting a homeotic conversion in the former. Phylogenetic analysis of
      Clermontia species based on 5S ribosomal DNA non-transcribed spacer sequences
      indicated a probable single and geologically recent origin of the double-corolla
      trait within the genus, with numerous potential reversals to the standard sepal
      petal format. Quantitative polymerase chain reaction analysis of homologs of the
      B-function genes PISTILLATA (PI), APETALA3 and TOMATO MADS 6 indicated ectopic
      expression of two PI paralogs in the first whorl of C. parviflora; no such
      homeotic expression was observed for the other two genes, nor for several other
      MADS box genes involved in various floral and non-floral functions. In the
      standard sepal-petal species C. arborescens, ectopic expression of PI homologs
      was not observed. In C. parviflora, the upregulation of PI homologs was precisely
      restricted to the perianth and stamen whorls, excluding a simple overexpression
      phenotype. In situ hybridization analysis of C. parviflora material similarly
      showed first and second whorl PI homolog expression in developing flower buds.
      CONCLUSIONS: Our morphological and gene expression data strongly suggest that a
      drastic and heritable phenotypic change, at the level of floral groundplan, can
      originate from a homeotic mutation that is likely regulatory, being under precise
      spatiotemporal control as opposed to having pleiotropic characteristics. The
      uniqueness of this trait among core eudicots could be linked to increased
      ecological viability in an unstable island environment, a chance event which need
      not have posed any immediate adaptive benefit. We argue that the evolutionarily
      young morphological radiation of Clermontia may form a model system for general
      understanding of mechanisms of larger-scale angiosperm diversification in past,
      similarly unstable environments, in which small regulatory changes may have been
      responsible for modern-day groundplan differences. TRIAL REGISTRATION: Clinical
      Trials.gov- NCT01710735 SIGNIFICANCE AND INNOVATIONS: The present investigation
      is one of the first to examine the hypothesis of gross muscle contractile
      inhibition due to the presence of diagnostically relevant MFTrPs. Individuals
      suffering from clinically relevant levels of self-reported pain are able to
      tolerate maximum voluntary contraction testing, but delayed onset muscle soreness
      (DOMS) is a likely side-effect irrespective of symptom status. As a consequence,
      its confounding effect during subsequent testing must be taken into account.

PMID- 23116180
TI  - ADP-ribose polymer depletion leads to nuclear Ctcf re-localization and chromatin
      rearrangement(1).
AB  - Ctcf (CCCTC-binding factor) directly induces Parp [poly(ADP-ribose) polymerase] 1
      activity and its PARylation [poly(ADPribosyl)ation] in the absence of DNA damage.
      Ctcf, in turn, is a substrate for this post-synthetic modification and as such it
      is covalently and non-covalently modified by PARs (ADP-ribose polymers).
      Moreover, PARylation is able to protect certain DNA regions bound by Ctcf from
      DNA methylation. We recently reported that de novo methylation of Ctcf target
      sequences due to overexpression of Parg [poly(ADP-ribose)glycohydrolase] induces
      loss of Ctcf binding. Considering this, we investigate to what extent PARP
      activity is able to affect nuclear distribution of Ctcf in the present study.
      Notably, Ctcf lost its diffuse nuclear localization following PAR (ADP-ribose
      polymer) depletion and accumulated at the periphery of the nucleus where it was
      linked with nuclear pore complex proteins remaining external to the perinuclear
      Lamin B1 ring. We demonstrated that PAR depletion-dependent perinuclear
      localization of Ctcf was due to its blockage from entering the nucleus. Besides
      Ctcf nuclear delocalization, the outcome of PAR depletion led to changes in
      chromatin architecture. Immunofluorescence analyses indicated DNA redistribution,
      a generalized genomic hypermethylation and an increase of inactive compared with
      active chromatin marks in Parg-overexpressing or Ctcf-silenced cells. Together
      these results underline the importance of the cross-talk between Parp1 and Ctcf
      in the maintenance of nuclear organization.

PMID- 23116181
TI  - Fucosterol is a selective liver X receptor modulator that regulates the
      expression of key genes in cholesterol homeostasis in macrophages, hepatocytes,
      and intestinal cells.
AB  - Fucosterol, a sterol that is abundant in marine algae, has hypocholesterolemic
      activity, but the mechanism underlying its effect is not clearly understood.
      Because data suggest that fucosterol can increase plasma high-density lipoprotein
      concentrations, we investigated whether it could activate liver X receptors
      (LXRs), critical transcription factors in reverse cholesterol transport.
      Fucosterol dose-dependently stimulated the transcriptional activity of both LXR
      alpha and -beta in a reporter gene assay, responses that were attenuated by the
      LXR antagonist As(2)O(3). Fucosterol also activated co-activator recruitment in
      cell-free time-resolved fluorescence resonance energy transfer analysis. In THP-1
      derived macrophages, it induced the transcriptional activation of ABCA1, ABCG1,
      and ApoE, key genes in reverse cholesterol transport, and thereby significantly
      increased the efflux of cholesterol. Fucosterol also regulated intestinal NPC1L1
      and ABCA1 in Caco-2 cells. Notably, fucosterol did not induce cellular
      triglyceride accumulation in HepG2 cells, primarily because of its upregulation
      of Insig-2a, which delays nuclear translocation of SREBP-1c, a key hepatic
      lipogenic transcription factor. These results suggest that fucosterol is a dual
      LXR agonist that regulates the expression of key genes in cholesterol homeostasis
      in multiple cell lines without inducing hepatic triglyceride accumulation.

PMID- 23116182
TI  - Dryland biological soil crust cyanobacteria show unexpected decreases in
      abundance under long-term elevated CO2.
AB  - Biological soil crusts (biocrusts) cover soil surfaces in many drylands globally.
      The impacts of 10 years of elevated atmospheric CO2 on the cyanobacteria in
      biocrusts of an arid shrubland were examined at a large manipulated experiment in
      Nevada, USA. Cyanobacteria-specific quantitative PCR surveys of cyanobacteria
      small-subunit (SSU) rRNA genes suggested a reduction in biocrust cyanobacterial
      biomass in the elevated CO2 treatment relative to the ambient controls.
      Additionally, SSU rRNA gene libraries and shotgun metagenomes showed reduced
      representation of cyanobacteria in the total microbial community. Taxonomic
      composition of the cyanobacteria was similar under ambient and elevated CO2
      conditions, indicating the decline was manifest across multiple cyanobacterial
      lineages. Recruitment of cyanobacteria sequences from replicate shotgun
      metagenomes to cyanobacterial genomes representing major biocrust orders also
      suggested decreased abundance of cyanobacteria sequences across the majority of
      genomes tested. Functional assignment of cyanobacteria-related shotgun metagenome
      sequences indicated that four subsystem categories, three related to oxidative
      stress, were differentially abundant in relation to the elevated CO2 treatment.
      Taken together, these results suggest that elevated CO2 affected a generalized
      decrease in cyanobacteria in the biocrusts and may have favoured cyanobacteria
      with altered gene inventories for coping with oxidative stress.

PMID- 23116184
TI  - Models for mirror symmetry breaking via beta-sheet-controlled copolymerization:
      (i) mass balance and (ii) probabilistic treatment.
AB  - Experimental mechanisms that yield the growth of homochiral copolymers over their
      heterochiral counterparts have been advocated by Lahav and co-workers. These
      chiral amplification mechanisms proceed through racemic beta-sheet-controlled
      polymerization operative in both surface crystallites as well as in solution. We
      develop two complementary theoretical models for these template-induced
      desymmetrization processes leading to multicomponent homochiral copolymers.
      First, assuming reversible beta-sheet formation, the equilibrium between the free
      monomer pool and the polymer strand within the template is assumed. This yields
      coupled nonlinear mass balance equations whose solutions are used to calculate
      enantiomeric excesses and average lengths of the homochiral chains formed. The
      second approach is a probabilistic treatment based on random polymerization. The
      occlusion probabilities depend on the polymerization activation energies for each
      monomer species and are proportional to the concentrations of the monomers in
      solution in the constant pool approximation. The monomer occlusion probabilities
      are represented geometrically in terms of unit simplexes from which conditions
      for maximizing or minimizing the likelihood for mirror symmetry breaking can be
      determined.

PMID- 23116183
TI  - Interaction of bovine serum albumin and lysozyme with stainless steel studied by
      time-of-flight secondary ion mass spectrometry and X-ray photoelectron
      spectroscopy.
AB  - An in-depth mechanistic understanding of the interaction between stainless steel
      surfaces and proteins is essential from a corrosion and protein-induced metal
      release perspective when stainless steel is used in surgical implants and in food
      applications. The interaction between lysozyme (LSZ) from chicken egg white and
      bovine serum albumin (BSA) and AISI 316L stainless steel surfaces was studied ex
      situ by means of X-ray photoelectron spectroscopy (XPS) and time-of-flight
      secondary ion mass spectrometry (ToF-SIMS) after different adsorption time
      periods (0.5, 24, and 168 h). The effect of XPS measurements, storage (aging),
      sodium dodecyl sulfate (SDS), and elevated temperature (up to 200  degrees C) on
      the protein layers, as well as changes in surface oxide composition, were
      investigated. Both BSA and LSZ adsorption induced an enrichment of chromium in
      the oxide layer. BSA induced significant changes to the entire oxide, while LSZ
      only induced a depletion of iron at the utmost layer. SDS was not able to remove
      preadsorbed proteins completely, despite its high concentration and relatively
      long treatment time (up to 36.5 h), but induced partial denaturation of the
      protein coatings. High-temperature treatment (200  degrees C) and XPS exposure (X
      ray irradiation and/or photoelectron emission) induced significant denaturation
      of both proteins. The heating treatment up to 200  degrees C removed some
      proteins, far from all. Amino acid fragment intensities determined from ToF-SIMS
      are discussed in terms of significant differences with adsorption time, between
      the proteins, and between freshly adsorbed and aged samples. Stainless steel
      protein interactions were shown to be strong and protein-dependent. The findings
      assist in the understanding of previous studies of metal release and surface
      changes upon exposure to similar protein solutions.

PMID- 23116185
TI  - Use of systemic glucocorticoids and the risk of colorectal cancer.
AB  - BACKGROUND: Systemic glucocorticoids are potent immunosuppressants, potentially
      facilitating carcinogenesis. Studies examining glucocorticoids and colorectal
      cancer risk are few. AIM: To investigate the association between use of systemic
      glucocorticoids and colorectal cancer risk, both overall and by cancer stage
      (localised versus metastatic). METHODS: We conducted a nested population-based
      case-control study in Northern Denmark (1.8 million people) using medical
      registries. The study included 14,158 patients with a first-time diagnosis of
      colorectal cancer from 1991 through 2010. Using risk set sampling, we identified
      141,580 population controls, matched on age and gender. Logistic regression
      models were used to compute odds ratios (ORs) and 95% confidence intervals (CIs),
      adjusting for covariates. RESULTS: Frequent use of systemic glucocorticoids
      (defined as >2 prescriptions) was not associated with overall colorectal cancer
      risk [adjusted OR (aOR) = 0.93 (95% CI: 0.85-1.00)], compared with never/rare use
      (<=2 prescriptions). Associations according to duration of use and doses
      (quartiles of cumulative prednisolone equivalents) were also near the null.
      Examining colorectal cancer by stage, no substantial associations were found
      between long-term use (>5 years) of high-dose (>5500 mg) systemic glucocorticoids
      and localised [aOR = 1.12 (95% CI: 0.81-1.55)] or metastatic [aOR = 0.82 (95% CI:
      0.59-1.14)] cancer. CONCLUSION: Despite immunological and metabolic effects of
      frequent use of systemic glucocorticoids, which would be expected to increase
      colorectal cancer risk, we found no substantial association between the two.

PMID- 23116186
TI  - Design and optimization of pyrazinecarboxamide-based inhibitors of diacylglycerol
      acyltransferase 1 (DGAT1) leading to a clinical candidate
      dimethylpyrazinecarboxamide phenylcyclohexylacetic acid (AZD7687).
AB  - A new series of pyrazinecarboxamide DGAT1 inhibitors was designed to address the
      need for a candidate drug with good potency, selectivity, and physical and DMPK
      properties combined with a low predicted dose in man. Rational design and
      optimization of this series led to the discovery of compound 30 (AZD7687), which
      met the project objectives for potency, selectivity, in particular over ACAT1,
      solubility, and preclinical PK profiles. This compound showed the anticipated
      excellent pharmacokinetic properties in human volunteers.

PMID- 23116187
TI  - Dynamic quantum molecular sieving separation of D2 from H2-D2 mixture with
      nanoporous materials.
AB  - Quantum molecular sieving separability of D(2) from an H(2)-D(2) mixture was
      measured at 77 K for activated carbon fiber, carbon molecular sieve, zeolite and
      single wall carbon nanotube using a flow method. The amount of adsorbed D(2) was
      evidently larger than H(2) for all samples. The maximum adsorption ratio
      difference between D(2) and H(2) was 40% for zeolite (MS13X), yielding a
      selectivity for D(2) with respect to H(2) of 3.05.

PMID- 23116188
TI  - Defining, measuring, and improving surgical quality: beyond teamwork and
      checklists to systems redesign and transformation.
AB  - BACKGROUND: Surgical complications are multifactorial but often are attributable
      to deficiencies in the quality of care. This review examines how quality is
      defined in surgery, the modalities employed to measure quality, and the
      approaches to improving the quality of surgical care. Beyond developing a
      hospital environment supportive of organizational learning, the next generation
      of surgical performance improvement will include broader, more innovative
      approaches. These ideas will create partnerships among patients, clinicians,
      industry, the arts, hospital leaders, and other sectors to look for ways to
      reinvent the system rather than simply to make a better hospital. METHODS: Review
      of pertinent English-language literature on surgical quality, definitions of
      quality, quality measures, performance improvement, and organizational learning
      in health care. RESULTS: Medical care should be safe, effective, patient
      centered, timely, efficient, and equitable, as defined by the Institute of
      Medicine core values for health care quality. There is substantive lack of
      agreement as to how to measure the quality of care. Although the goal of each
      measurement system is to give patients the ability to compare hospitals
      nationally, most of the methodologies measure widely different aspects of
      hospital care, resulting in conflicting illustrations of institutional
      performance and confounded decision making for patients and for purchasers of
      healthcare services and insurance. CONCLUSIONS: The best pathway for surgical
      quality and performance improvement includes the application of systems
      engineering and innovation to determine ways to do better what we do currently,
      and to improve the present system while developing ideas for better delivery of
      high-quality care in the future.

PMID- 23116190
TI  - Psychometric properties of the Cook Medley hostility scale and its association
      with inflammatory markers in African Americans.
AB  - Dispositional hostility as measured by the Cook Medley Hostility (Ho) Scale has
      been associated with inflammation and cardiovascular disease (CVD) risk. There is
      evidence that suggests that factors of hostility are more useful in predicting
      poor cardiovascular health outcomes than a single hostility construct. The
      purpose of this study was to investigate the latent factors of hostility and
      their association with inflammatory markers interleukin-6 (IL-6) and C-reactive
      protein (CRP) in an African-American community sample. This racial/ethnic group
      has been largely excluded from this line of research despite their
      disproportionate burden of CVD and its risk factors. Blood samples for plasma IL
      6 and CRP were collected on the same day the Ho Scale was administered. Plasma IL
      6 and CRP levels were determined using enzymatic-linked immunosorbent assay.
      Confirmatory factor analysis revealed three latent main factors of hostility:
      Neuroticism, Manichaeism and Moral Primitiveness, and seven intermediary
      subfactors. Of the subfactors, hostile affect was significantly associated with
      greater CRP levels and predatory self interest was significantly associated with
      greater IL-6 levels. Findings suggest that African Americans have a unique
      pattern of hostility and two latent subfactors are associated with a marker of
      CVD. Based on the findings, future studies should aim to further delineate how
      hostility influences health outcomes in African Americans. 

PMID- 23116191
TI  - Electron transfer at oxide surfaces. The MgO paradigm: from defects to ultrathin
      films.

PMID- 23116189
TI  - Minimizing risks and monitoring safety of an antenatal care intervention to
      mitigate domestic violence among young Indian women: The Dil Mil trial.
AB  - BACKGROUND: Domestic violence - physical, psychological, or sexual abuse
      perpetrated against women by one or more family members - is highly prevalent in
      India. However, relatively little research has been conducted on interventions
      with the potential to mitigate domestic violence and its adverse health
      consequences, and few resources exist to guide safety planning and monitoring in
      the context of intervention research. Dil Mil is a promising women's empowerment
      based intervention developed in India that engages with young women (daughters-in
      law) and their mothers-in-law to mitigate domestic violence and related adverse
      health outcomes. This paper describes the design of a randomized controlled trial
      of Dil Mil in Bengaluru, India, with a focus on strategies used to minimize study
      related risks and monitor safety. METHODS/DESIGN: A phase 2 randomized controlled
      trial using a parallel comparison of the Dil Mil intervention versus standard
      care will be implemented in three public primary health centers in Bengaluru.
      Young pregnant women in the first or second trimester of pregnancy will be
      recruited from antenatal services at study health centers and through community
      outreach. If eligible and willing, their mother-in-law will also be recruited.
      Once enrolled, dyads will participate in a baseline interview and then randomized
      either to the control arm and receive standard care or to the intervention arm
      and receive standard care plus the Dil Mil intervention. Additional evaluations
      will be conducted at 3 months and 6 months postpartum. Data will be analyzed to
      examine the feasibility and safety of the intervention and the effect of the
      intervention on intermediary outcomes (the empowerment of daughters-in-law and
      mothers-in-law), incidence of domestic violence among daughters-in-law, and
      health outcomes including perceived quality of life, psychosocial status and
      maternal and infant health outcomes. DISCUSSION: This study offers approaches
      that may help guide safety planning and monitoring in other domestic violence
      intervention trials in similar settings. Moreover, given the staggeringly high
      prevalence of domestic violence against young women in India (and indeed
      globally) and the dearth of data on effective interventions, this study is poised
      to make an important contribution to the evidence-base for domestic violence
      prevention. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01337778.

PMID- 23116192
TI  - Capturing the elasticity and morphology of live fibroblast cell cultures during
      degradation with atomic force microscopy.
AB  - Atomic force microscopy, in a liquid environment, was used to capture in vitro
      the morphological and mechanical changes that cultured fibroblasts undergo as
      time elapses from the completion of the cell culture. Topography images
      illustrated that initially, the nucleus had a height of 1.18 +/- 0.2 MUm, and
      after 48 h it had decreased to 550 +/- 60 nm; similarly, the cell membrane
      exhibited significant shrinkage from 34 +/- 4 to 23 +/- 2 MUm. After each image
      scan, atomic force microscopy indentation was performed on the centre of the
      nucleus, to measure the changes in the cell elasticity. Examination of the force
      distance curves indicated that the membrane elastic modulus at the nucleus
      remained the same within the time frame of 48 h, even though the cell morphology
      had significantly changed.

PMID- 23116193
TI  - Anti-Candida albicans effectiveness of citral and investigation of mode of
      action.
AB  - CONTEXT: Candidiasis is a mycosis caused by Candida species, which is of clinical
      importance due to the increase in resistant yeasts. Candida infection has been a
      serious health problem due to the inappropriate use of antibiotics. Therefore, it
      is necessary to study molecules with an antifungal action. Citral is a
      monoterpene with known pharmacological properties, including antimicrobial
      action. OBJECTIVE: The aim of this work was to determine the minimum inhibitory
      concentration (MIC) and minimum fungicidal concentration (MFC) of citral and the
      probable mode of action. MATERIALS AND METHODS: The MIC of citral was determined
      by the broth microdilution method using Sabouraud dextrose medium. Additionally,
      the interference of citral in cell wall (sorbitol assay) and the binding of
      citral to ergosterol and cholesterol were studied, carried out by broth
      microdilution method. RESULTS: The MIC and MFC of citral were 512 and 1024 ug/mL,
      respectively. The MIC of amphotericin B was 1 ug/mL. The mechanism of action did
      not involve either the cell wall or ergosterol. However, the presence of
      cholesterol increased the MIC of citral to 1024 ug/mL, indicating there is some
      interaction between citral and cholesterol. Amphotericin B was used as the
      positive control, and it showed a high MIC in the presence of ergosterol (32
      ug/mL), while in the presence of cholesterol MIC increased to 4 ug/mL.
      CONCLUSION: Citral inhibits the growth of C. albicans. The probable mechanism of
      action did not involve the cell wall or ergosterol. Citral is able to interact
      with cholesterol. More studies are necessary to describe their effects
      completely.

PMID- 23116194
TI  - Size-controlled anatase titania single crystals with octahedron-like morphology
      for dye-sensitized solar cells.
AB  - A simple hydrothermal method with titanium tetraisopropoxide (TTIP) as a
      precursor and triethanolamine (TEOA) as a chelating agent enabled growth in the
      presence of a base (diethylamine, DEA) of anatase titania nanocrystals (HD1-HD5)
      of controlled size. DEA played a key role to expedite this growth, for which a
      biphasic crystal growth mechanism is proposed. The produced single crystals of
      titania show octahedron-like morphology with sizes in a broad range of 30-400 nm;
      a typical, extra large, octahedral single crystal (HD5) of length 410 nm and
      width 260 nm was obtained after repeating a sequential hydrothermal treatment
      using HD3 and then HD4 as a seed crystal. The nanocrystals of size ~30 nm (HD1)
      and ~300 nm (HD5) served as active layer and scattering layer, respectively, to
      fabricate N719-sensitized solar cells. These HD devices showed greater V(OC) than
      devices of conventional nanoparticle (NP) type; the overall device performance of
      HD attained an efficiency of 10.2% power conversion at a total film thickness of
      28 MUm, which is superior to that of a NP-based reference device (eta = 9.6%)
      optimized at a total film thickness of 18-20 MUm. According to results obtained
      from transient photoelectric and charge extraction measurements, this superior
      performance of HD devices relative to their NP counterparts is due to the more
      rapid electron transport and greater TiO(2) potential.

PMID- 23116195
TI  - Lateral gene transfer of an ABC transporter complex between major constituents of
      the human gut microbiome.
AB  - BACKGROUND: Several links have been established between the human gut microbiome
      and conditions such as obesity and inflammatory bowel syndrome. This highlights
      the importance of understanding what properties of the gut microbiome can affect
      the health of the human host. Studies have been undertaken to determine the
      species composition of this microbiome and infer functional profiles associated
      with such host properties. However, lateral gene transfer (LGT) between community
      members may result in misleading taxonomic attributions for the recipient
      organisms, thus making species-function links difficult to establish. RESULTS: We
      identified a peptides/nickel transport complex whose components differed in
      abundance based upon levels of host obesity, and assigned the encoded proteins to
      members of the microbial community. Each protein was assigned to several distinct
      taxonomic groups, with moderate levels of agreement observed among different
      proteins in the complex. Phylogenetic trees of these proteins produced clusters
      that differed greatly from taxonomic attributions and indicated that habitat
      directed LGT of this complex is likely to have occurred, though not always
      between the same partners. CONCLUSIONS: These findings demonstrate that certain
      membrane transport systems may be an important factor within an obese-associated
      gut microbiome and that such complexes may be acquired several times by different
      strains of the same species. Additionally, an example of individual proteins from
      different organisms being transferred into one operon was observed, potentially
      demonstrating a functional complex despite the donors of the subunits being
      taxonomically disparate. Our results also highlight the potential impact of
      habitat-directed LGT on the resident microbiota.

PMID- 23116196
TI  - Is the polycystic ovary syndrome the causative of the increase in inflammatory
      markers and metabolic risk?
AB  - AIMS: To investigate the relationship between the levels of C-reactive protein
      (CRP), interleukin-6 (IL-6) and IL-1beta and the hormonal and metabolic
      alterations in women with polycystic ovary syndrome (PCO). MATERIALS AND METHODS:
      Case-control study. CRP, IL-6 and IL-1beta were evaluated in combination with
      obesity, insulin resistance (IR) and hyperandrogenism parameters in 20 patients
      with PCO. Twenty healthy women were used as the control. RESULTS: The average CRP
      values was 5.1 in the cases vs. 0.8 mg/L in the control group (p < 0.0001). The
      IL-6 average values were 2.77 in the cases vs. 2.70 pg/ml in the control group (p
      = 0.254). IL-1beta levels were found to be within the normal range in all
      individuals. A positive correlation was found between the CRP values and the IR
      (p < 0.0001) as well as with the presence of obesity (p < 0.02). No correlation
      was found between PCR and hyperandrogenemia (p = 0.4) nor between IL-6 values and
      IR (p = 0.3), or between the levels of this cytokine and the presence of
      hyperandrogenemia (p = 0.2). A significant correlation was found between IL-6
      levels and obesity (p < 0.0001). CONCLUSIONS: The present study demonstrates the
      presence of a chronic inflammation status in young women with PCO. These
      parameters are mainly related to obesity and, to a lesser extent, to IR.

PMID- 23116198
TI  - Reading impairment in an adolescent with temporo-occipital epilepsy. Pre- and
      post-surgical evaluation.
AB  - We present a 16 year-old right-handed case who underwent a left temporo-occipital
      resection to treat intractable epilepsy. Pre- and post-surgical evaluations
      showed an average intellectual quotient, preserved abilities in language and
      visuo-spatial functions and increased reading and spelling deficits (difficulties
      with irregular words, homophones and phonologically valid spelling errors of
      irregularly spelled words, associated with preserved performances in non-words).
      This pattern of characteristic lexical route deficits highlights the major role
      of the temporo-occipital areas in reading acquisition. We discussed the
      consequences of temporo-occipital dysfunction on reading. 

PMID- 23116197
TI  - Proteomics-based analysis of invasion-related proteins in malignant gliomas.
AB  - One of the insidious biological features of gliomas is their potential to
      extensively invade normal brain tissue, yet molecular mechanisms that dictate
      this locally invasive behavior remain poorly understood. To investigate the
      molecular basis of invasion by malignant gliomas, proteomic analysis was
      performed using a pair of canine glioma subclones - J3T-1 and J3T-2 - that show
      different invasion phenotypes in rat brains but have similar genetic backgrounds.
      Two-dimensional protein electrophoresis of whole-cell lysates of J3T-1
      (angiogenesis-dependent invasion phenotype) and J3T-2 (angiogenesis-independent
      invasion phenotype) was performed. Twenty-two distinct spots were recognized when
      significant alteration was defined as more than 1.5-fold change in spot intensity
      between J3T-1 and J3T-2. Four proteins that demonstrated increased expression in
      J3T-1, and 14 proteins that demonstrated increased expression in J3T-2 were
      identified using liquid chromatography-mass spectrometry analysis. One of the
      proteins identified was annexin A2, which was expressed at higher levels in J3T-1
      than in J3T-2. The higher expression of annexin A2 in J3T-1 was corroborated by
      quantitative RT-PCR of the cultured cells and immunohistochemical staining of the
      rat brain tumors. Moreover, immunohistochemical analysis of human glioblastoma
      specimens showed that annexin A2 was expressed at high levels in the tumor cells
      that formed clusters around dilated vessels. These results reveal differences in
      the proteomic profiles between these two cell lines that might correlate with
      their different invasion profiles. Thus, annexin A2 may be related to
      angiogenesis-dependent invasion.

PMID- 23116199
TI  - Analysis of protein expression profiles in the thymus of chickens infected with
      Marek's disease virus.
AB  - BACKGROUND: Marek's disease virus (MDV) is a highly cell-associated oncogenic
      alpha-herpesvirus that causes a disease characterised by T-cell lymphomas. The
      pathogenesis, or the nature of the interaction of the virus and the host, in the
      thymus are still unclear. RESULTS: In this study, we identified 119
      differentially expressed proteins using two-dimensional electrophoresis and mass
      spectrometry from the thymuses of chickens infected with the RB1B strain of MDV.
      These differentially expressed proteins were found mainly at 21, 28 and 35 days
      post-infection. More than 20 of the differentially expressed proteins were
      directly associated with immunity, apoptosis, tumour development and viral
      infection and replication. Five of these proteins, ANXA1, MIF, NPM1, OP18 and
      VIM, were further confirmed using real-time PCR. The functional associations and
      roles in oncogenesis of these proteins are discussed. CONCLUSIONS: This work
      provides a proteomic profiling of host responses to MDV in the thymus of chickens
      and further characterises proteins related to the mechanisms of MDV oncogenesis
      and pathogenesis.

PMID- 23116201
TI  - Peach fruit: metabolic comparative analysis of two varieties with different
      resistances to insect attacks by NMR spectroscopy.
AB  - The metabolite profile of aqueous extracts of two peach varieties, Percoca
      Romagnola 7 and Flaminia, with different susceptibilities to  Ceratitis capitata 
      attack was investigated by means of 1D and 2D high-field NMR spectroscopy. Water
      soluble metabolites belonging to different classes such as organic acids (citric,
      fumaric, malic, quinic, shikimic, and succinic acids), sugars (fucose, fructose,
      fructose-6-phosphate, glucose, glucose-6-phosphate, rhamnose, sucrose, and
      xylose), amino acids (alanine, asparagine, isoleucine, threonine, and valine) and
      other metabolites such as myo-inositol, choline, trigonelline, catechin,
      chlorogenic and neochlorogenic acids, orthophosphate, and alpha-l
      glycerophosphorylcholine were identified. The metabolite profile together with a
      suitable statistical analysis was used to make a comparison between the two
      varieties. The levels of glucose, xylose, myo-inositol, choline, isoleucine, and
      valine were found to be higher in Flaminia than in Percoca Romagnola 7 samples,
      whereas the levels of fumaric acid, alanine, quinic acid, sucrose, fucose, and
      chlorogenic and neochlorogenic acid were found to be higher in Percoca Romagnola
      7 than in Flaminia samples.

PMID- 23116200
TI  - New insight into the functions of the interleukin-17 receptor adaptor protein
      Act1 in psoriatic arthritis.
AB  - Recent genome-wide association studies have implicated the tumor necrosis factor
      receptor-associated factor 3-interacting protein 2 (TRAF3IP2) gene and its
      product, nuclear factor-kappa-B activator 1 (Act1), in the development of
      psoriatic arthritis (PsA). The high level of sequence homology of the TRAF3IP2
      (Act1) gene across the animal kingdom and the presence of the Act1 protein in
      multiple cell types strongly suggest that the protein is of importance in normal
      cellular function. Act1 is an adaptor protein for the interleukin-17 (IL-17)
      receptor, and recent observations have highlighted the significance of IL-17
      signaling and localized inflammation in autoimmune diseases. This review
      summarizes data from recent genome-wide association studies as well as
      immunological and molecular investigations of Act1. Together, these studies
      provide new insight into the role of IL-17 signaling in PsA. It is well
      established that IL-17 activation of tumor necrosis factor receptor-associated
      factor 6 (TRAF6) signaling pathways normally leads to nuclear factor-kappa-B
      mediated inflammation. However, the dominant PsA-associated TRAF3IP2 (Act1) gene
      single-nucleotide polymorphism (rs33980500) results in decreased binding of Act1
      to TRAF6. This key mutation in Act1 could lead to a greater association of the IL
      17 receptor with TRAF2/TRAF5 and this in turn suggests an alternative function
      for IL-17 in PsA. The recent observations described and discussed in this review
      raise the clinically significant possibility of redefining the immunological role
      of IL-17 in PsA and provide a basis for defining future studies to elucidate the
      molecular and cellular functions of Act1. 

PMID- 23116202
TI  - nde1 deletion improves mitochondrial DNA maintenance in Saccharomyces cerevisiae
      coenzyme Q mutants.
AB  - Saccharomyces cerevisiae has three distinct inner mitochondrial membrane NADH
      dehydrogenases mediating the transfer of electrons from NADH to CoQ (coenzyme Q):
      Nde1p, Nde2p and Ndi1p. The active site of Ndi1p faces the matrix side, whereas
      the enzymatic activities of Nde1p and Nde2p are restricted to the intermembrane
      space side, where they are responsible for cytosolic NADH oxidation. In the
      present study we genetically manipulated yeast strains in order to alter the
      redox state of CoQ and NADH dehydrogenases to evaluate the consequences on mtDNA
      (mitochondrial DNA) maintenance. Interestingly, nde1 deletion was protective for
      mtDNA in strains defective in CoQ function. Additionally, the absence of
      functional Nde1p promoted a decrease in the rate of H2O2 release in isolated
      mitochondria from different yeast strains. On the other hand, overexpression of
      the predominant NADH dehydrogenase NDE1 elevated the rate of mtDNA loss and was
      toxic to coq10 and coq4 mutants. Increased CoQ synthesis through COQ8
      overexpression also demonstrated that there is a correlation between CoQ
      respiratory function and mtDNA loss: supraphysiological CoQ levels were
      protective against mtDNA loss in the presence of oxidative imbalance generated by
      Nde1p excess or exogenous H2O2. Altogether, our results indicate that impairment
      in the oxidation of cytosolic NADH by Nde1p is deleterious towards mitochondrial
      biogenesis due to an increase in reactive oxygen species release.

PMID- 23116203
TI  - Nanoparticles with a bicontinuous cubic internal structure formed by cationic and
      non-ionic surfactants and an anionic polyelectrolyte.
AB  - Nanoparticles with an internal structure have been prepared by dispersing under
      dilute conditions poly(acrylic acid) with a polymerization degree n = 6000
      (PAA6000) together with a cationic surfactant hexadecyltrimethylammonium
      hydroxide (C16TAOH) and the non-ionic surfactant penta(ethylene glycol)
      monododecyl ether (C12E5) in water. The nanoparticles are formed at different
      mixing ratios in the corresponding two-phase regions (liquid crystalline
      phase/dilute isotropic phase) of the C16TAPA6000 complex salt/C12E5/water ternary
      phase diagram. The particles consist of polyacrylate PA6000- polyions, C16TA+
      surfactant ions, and C12E5. Their internal ordering was identified by small-angle
      X-ray scattering (SAXS) to be either bicontinuous cubic with the Ia3d
      crystallographic space group or normal hexagonal depending upon the amount of
      C12E5. The bicontinuous cubic phase, to our knowledge never observed before in
      polyelectrolyte-surfactant particle systems, was inferred by SAXS experiments.
      The data also showed that this structure is thermoresponsive in a reversible
      manner. The bicontinuous cubic space group transforms from Ia3d to Im3m as the
      temperature decreases from 25 to 15  degrees C. According to dynamic light
      scattering and electrophoretic mobility measurements, the particles have a well
      defined size (apparent hydrodynamic radii RH in the range of 88-140 nm) and carry
      a positive net charge. The size of the nanoparticles is stable up to 1 month. The
      faceted nanoparticles are visualized by cryogenic transmission electron
      microscopy that also reveals their coexistence with thread-like C12E5 micelles.

PMID- 23116204
TI  - Are depression and anxiety determinants or indicators of quality of life in
      breast cancer patients?
AB  - Depression and anxiety are associated with a decline of health-related quality of
      life (QoL) in breast cancer patients, and the present study aims to investigate
      the longitudinal relationship of depression and anxiety with QoL in breast cancer
      patients. Depression and anxiety (HADS) as well as QoL (EORTC QLQ-C30) were
      assessed at baseline and six-month follow-up in 118 breast cancer patients and
      analysed using cross-lagged partial correlation analysis (CLPC). There were
      significant partial correlations between depression and anxiety at baseline and
      physical functioning, emotional functioning and "global health and QoL" at six
      month follow-up (range of pr = -0.197 and -0.392; p < 0.05). "Global health and
      QoL" at baseline was significantly correlated with depression and anxiety at
      follow-up (pr = -0.207 and -0.327; p < 0.05). Cognitive functioning at baseline
      was significantly associated with anxiety at follow-up (pr = -0.248; p < 0.01).
      CLPC analysis of two models (depression and anxiety determining QoL vs. QoL
      determining depression and anxiety) did not show significant results. Hence, in
      breast cancer patients, depression and anxiety are closely related to QoL and the
      observed correlations suggest a complex interrelation in which depression and
      anxiety have to be regarded as indicators of QoL rather than determinants. 

PMID- 23116205
TI  - Competition reactions of H2O*+ radical in concentrated Cl- aqueous solutions:
      picosecond pulse radiolysis study.
AB  - Picosecond pulse-probe radiolysis measurements of highly concentrated Cl(-)
      aqueous solutions are used to probe the oxidation mechanism of the Cl(-). The
      transient absorption spectra are measured from 340 to 710 nm in the picosecond
      range for the ultrafast electron pulse radiolysis of halide solutions at
      different concentrations up to 8 M. The amount of Cl(2)(*-) formation within the
      electron pulse increases notably with increasing Cl(-) concentration. Kinetic
      measurements reveal that the direct ionization of Cl(-) cannot solely explain the
      significant amount of fast Cl(2)(*-) formation within the electron pulse. The
      results suggest that Cl(-) reacts with the precursor of the OH(*) radical, i.e.,
      H(2)O(*+) radical, to form Cl(*) atom within the electron pulse and the Cl(*)
      atom reacts subsequently with Cl(-) to form Cl(2)(*-) on very short time scales.
      The proton transfer reaction between H(2)O(*+) and the water molecule competes
      with the electron transfer reaction between Cl(-) and H(2)O(*+). Molecular
      dynamics simulations show that number of water molecules in close proximity
      decreases with increasing concentration of the salt (NaCl), confirming that for
      highly concentrated solutions the proton transfer reaction between H(2)O(*+) and
      a water molecule becomes less efficient. Diffusion-kinetic simulations of spur
      reactions including the direct ionization of Cl(-) and hole scavenging by Cl(-)
      show that up to 30% of the H(2)O(*+) produced by the irradiation could be
      scavenged for solutions containing 5.5 M Cl(-). This process decreases the yield
      of OH(*) radical in solution on the picosecond time scale. The experimental
      results for the same concentration of Cl(-) at a given absorbed dose show that
      the radiation energy absorbed by counterions is transferred to Cl(-) or water
      molecules and the effect of the countercation such as Li(+), K(+), Na(+), and
      Mg(2+) on the oxidation yield of Cl(-) is negligible.

PMID- 23116206
TI  - Absolute configuration of isosilybin A by X-ray crystallography of the heavy atom
      analogue 7-(4-Bromobenzoyl)isosilybin A.
AB  - Isosilybin A (1) is one of the major flavonolignans that constitute silymarin, an
      extract of the fruits (achenes) of milk thistle (Silybum marianum). The chemistry
      of the Silybum flavonolignans has been studied for over four decades, and the
      absolute configuration of 1 has been determined previously by electronic circular
      dichroism and X-ray crystallography via correlating the relative configuration of
      the phenylpropanoid moiety to the established absolute configuration of the 3
      hydroxyflavanone portion of the molecule. Herein we report the X-ray
      crystallographic structure of the product of the reaction of 1 with 4
      bromobenzoyl chloride, and, thus, the absolute configuration of 1 was established
      as (2R, 3R, 7"R, 8"R) directly via X-ray crystallography of an analogue that
      incorporated a heavy atom. The results were consistent with previously reported
      assignments and verified the absolute configuration of the diastereoisomer of 1,
      isosilybin B, and the related diastereoisomeric regioisomers, silybin A and
      silybin B. 

PMID- 23116207
TI  - Chiral surfactant-type catalyst for asymmetric reduction of aliphatic ketones in
      water.
AB  - A novel chiral surfactant-type catalyst is developed. Micelles formed in water by
      association of the catalysts themselves, and this was confirmed by TEM analyses.
      Asymmetric transfer hydrogenation of aliphatic ketones catalyzed by the chiral
      metallomicellar catalyst gave good to excellent conversions and remarkable
      stereoselectivities (up to 95% ee). Synergistic effects between the metal
      catalyzed center and the hydrophobic microenvironment of the core in the
      metallomicelle led to high enantioselectivities.

PMID- 23116208
TI  - Randomised clinical trials: linaclotide phase 3 studies in IBS-C - a prespecified
      further analysis based on European Medicines Agency-specified endpoints.
AB  - BACKGROUND: Treatment options that improve overall symptoms of irritable bowel
      syndrome with constipation (IBS-C) are lacking. AIM: A prespecified further
      analysis to evaluate the efficacy and safety of linaclotide, a guanylate cyclase
      C agonist, in patients with IBS-C, based on efficacy parameters prespecified for
      European Medicines Agency (EMA) submission. METHODS: Two randomised, double
      blind, multicentre Phase 3 trials investigated once-daily linaclotide (290 MUg)
      for 12 weeks (Trial 31) or 26 weeks (Trial 302) in patients with IBS-C.
      Prespecified primary endpoints were the EMA-recommended co-primary endpoints: (i)
      12-week abdominal pain/discomfort responders [>=30% reduction in mean abdominal
      pain and/or discomfort score (11-point scales), with neither worsening from
      baseline, for >=6 weeks] and (ii) 12-week IBS degree-of-relief responders
      (symptoms 'considerably' or 'completely' relieved for >=6 weeks). RESULTS:
      Overall, 803 (Trial 31) and 805 patients (Trial 302) were randomised. A
      significantly greater proportion of linaclotide-treated vs. placebo-treated
      patients were 12-week abdominal pain/discomfort responders (Trial 31: 54.8% vs.
      41.8%; Trial 302: 54.1% vs. 38.5%; P < 0.001) and IBS degree-of-relief responders
      (Trial 31: 37.0% vs. 18.5%; Trial 302: 39.4% vs. 16.6%; P < 0.0001). Similarly,
      significantly more linaclotide- vs. placebo-treated patients were responders for
      >=13 weeks in Trial 302 (abdominal pain/discomfort: 53.6% vs. 36.0%; IBS degree
      of-relief: 37.2% vs. 16.9%; P < 0.0001). The proportion of sustained responders
      (co-primary endpoint responders plus responders for >=2 of the last 4 weeks of
      treatment) was also significantly greater with linaclotide vs. placebo in both
      trials (P < 0.001). CONCLUSION: Linaclotide treatment significantly improved
      abdominal pain/discomfort and degree-of-relief of IBS-C symptoms compared with
      placebo over 12 and 26 weeks. TRIAL REGISTRATION: ClinicalTrials.gov
      (identifiers: NCT00948818 and NCT00938717).

PMID- 23116209
TI  - 'Candidatus Ancillula trichonymphae', a novel lineage of endosymbiotic
      Actinobacteria in termite gut flagellates of the genus Trichonympha.
AB  - Termite gut flagellates are colonized by host-specific lineages of ectosymbiotic
      and endosymbiotic bacteria. Previous studies have shown that flagellates of the
      genus Trichonympha may harbour more than one type of symbiont. Using a
      comprehensive approach that combined cloning of SSU rRNA genes with fluorescence
      in situ hybridization and electron microscopy, we investigated the phylogeny and
      subcellular locations of the symbionts in a variety of Trichonympha species from
      different termites. The flagellates in Trichonympha Cluster I were the only
      species associated with 'Endomicrobia', which were located in the posterior part
      of the cell, confirming previous results. Trichonympha species of Cluster II from
      the termite genus Incisitermes (family Kalotermitidae) lacked 'Endomicrobia' and
      were associated with endosymbiotic Actinobacteria, which is highly unusual. The
      endosymbionts, for which we suggest the name 'Candidatus Ancillula
      trichonymphae', represent a novel, deep-branching lineage in the Micrococcineae
      that consists exclusively of clones from termite guts. They preferentially
      colonized the anterior part of the flagellate host and were highly abundant in
      all species of Trichonympha Cluster II except Trichonympha globulosa. Here, they
      were outnumbered by a Desulfovibrio species associated with the cytoplasmic
      lamellae at the anterior cell pole. Such symbionts are present in both
      Trichonympha clusters, but not in all species. Unlike the intracellular location
      reported for the Desulfovibrio symbionts of Trichonympha agilis (Cluster I), the
      Desulfovibrio symbionts of T. globulosa (Cluster II) were situated in deep
      invaginations of the plasma membrane that were clearly connected to the exterior
      of the host cell.

PMID- 23116211
TI  - Highly stable porous silicon-carbon composites as label-free optical biosensors.
AB  - A stable, label-free optical biosensor based on a porous silicon-carbon (pSi-C)
      composite is demonstrated. The material is prepared by electrochemical
      anodization of crystalline Si in an HF-containing electrolyte to generate a
      porous Si template, followed by infiltration of poly(furfuryl) alcohol (PFA) and
      subsequent carbonization to generate the pSi-C composite as an optically smooth
      thin film. The pSi-C sensor is significantly more stable toward aqueous buffer
      solutions (pH 7.4 or 12) compared to thermally oxidized (in air, 800  degrees C),
      hydrosilylated (with undecylenic acid), or hydrocarbonized (with acetylene, 700 
      degrees C) porous Si samples prepared and tested under similar conditions.
      Aqueous stability of the pSi-C sensor is comparable to related optical biosensors
      based on porous TiO(2) or porous Al(2)O(3). Label-free optical interferometric
      biosensing with the pSi-C composite is demonstrated by detection of rabbit IgG on
      a protein-A-modified chip and confirmed with control experiments using chicken
      IgG (which shows no affinity for protein A). The pSi-C sensor binds significantly
      more of the protein A capture probe than porous TiO(2) or porous Al(2)O(3), and
      the sensitivity of the protein-A-modified pSi-C sensor to rabbit IgG is found to
      be ~2* greater than label-free optical biosensors constructed from these other
      two materials.

PMID- 23116210
TI  - Kalrn plays key roles within and outside of the nervous system.
AB  - BACKGROUND: The human KALRN gene, which encodes a complex, multifunctional Rho
      GDP/GTP exchange factor, has been linked to cardiovascular disease, psychiatric
      disorders and neurodegeneration. Examination of existing Kalrn knockout mouse
      models has focused only on neuronal phenotypes. However, Kalirin was first
      identified through its interaction with an enzyme involved in the synthesis and
      secretion of multiple bioactive peptides, and studies in C.elegans revealed roles
      for its orthologue in neurosecretion. RESULTS: We used a broad array of tests to
      evaluate the effects of ablating a single exon in the spectrin repeat region of
      Kalrn (KalSR(KO/KO)); transcripts encoding Kalrn isoforms containing only the
      second GEF domain can still be produced from the single remaining functional
      Kalrn promoter. As expected, KalSR(KO/KO) mice showed a decrease in anxiety-like
      behavior and a passive avoidance deficit. No changes were observed in prepulse
      inhibition of acoustic startle or tests of depression-like behavior. Growth rate,
      parturition and pituitary secretion of growth hormone and prolactin were
      deficient in the KalSR(KO/KO) mice. Based on the fact that a subset of Kalrn
      isoforms is expressed in mouse skeletal muscle and the observation that muscle
      function in C.elegans requires its Kalrn orthologue, KalSR(KO/KO) mice were
      evaluated in the rotarod and wire hang tests. KalSR(KO/KO) mice showed a profound
      decrease in neuromuscular function, with deficits apparent in KalSR(+/KO) mice;
      these deficits were not as marked when loss of Kalrn expression was restricted to
      the nervous system. Pre- and postsynaptic deficits in the neuromuscular junction
      were observed, along with alterations in sarcomere length. CONCLUSIONS: Many of
      the widespread and diverse deficits observed both within and outside of the
      nervous system when expression of Kalrn is eliminated may reflect its role in
      secretory granule function and its expression outside of the nervous system.

PMID- 23116212
TI  - The Push-Turn-Taptap task outperforms measures of executive functioning in
      predicting declines in functionality: evidence-based approach to test validation.
AB  - Performance on the Push-Turn-Taptap (PTT) task has been shown to be a strong
      predictor of concurrent everyday functioning. This study utilized a prospective,
      longitudinal design to evaluate the PTT task for predicting future performance on
      a behavioral assessment of everyday functioning. The PTT task was compared to
      other measures of executive functioning as well as general cognition in terms of
      administration time and ability to identify participants who evidenced functional
      decline. A total of 50 community-dwelling older adults (ages 58-87) completed the
      PTT task, Mattis Dementia Rating Scale, Geriatric Depression Scale, Behavioral
      Dyscontrol Scale, Delis-Kaplan Executive Function System, and Timed Instrumental
      Activities of Daily Living. Baseline PTT performance (a) was highly correlated
      with an objective measure of everyday functioning after approximately one year (r
      = -.497, p < .001), (b) was associated with changes in follow-up functioning,
      F(3, 46) = 3.15, p = .03, (c) was a better predictor of future functional status
      than a longer battery of EF, and (d) reliably identified individuals with the
      greatest magnitude of functional decline. The PTT tasks may provide a
      particularly advantageous method of predicting future changes in everyday
      functioning in older adults.

PMID- 23116213
TI  - NHS health checks through general practice: randomised trial of population
      cardiovascular risk reduction.
AB  - BACKGROUND: The global burden of the major vascular diseases is projected to rise
      and to remain the dominant non-communicable disease cluster well into the twenty
      first century. The Department of Health in England has developed the NHS Health
      Check service as a policy initiative to reduce population vascular disease risk.
      The aims of this study were to monitor population changes in cardiovascular
      disease (CVD) risk factors over the first year of the new service and to assess
      the value of tailored lifestyle support, including motivational interview with
      ongoing support and referral to other services. METHODS: Randomised trial
      comparing NHS Health Check service only with NHS Health Check service plus
      additional lifestyle support in Stoke on Trent, England. Thirty eight general
      practices and 601 (365 usual care, 236 additional lifestyle support) patients
      were recruited and randomised independently between September 2009 and February
      2010. Changes in population CVD risk between baseline and one year follow-up were
      compared, using intention-to-treat analysis. The primary outcome was the
      Framingham 10 year CVD risk score. Secondary outcomes included individual
      modifiable risk measures and prevalence of individual risk categories. Additional
      lifestyle support included referral to a lifestyle coach and free sessions as
      needed for: weight management, physical activity, cook and eat and positive
      thinking. RESULTS: Average population CVD risk decreased from 32.9% to 29.4% (p
      <0.001) in the NHS Health Check only group and from 31.9% to 29.2% (p <0.001) in
      the NHS Health Check plus additional lifestyle support group. There was no
      significant difference between the two groups at either measurement point.
      Prevalence of high blood pressure, high cholesterol and smoking were reduced
      significantly (p <0.01) in both groups. Prevalence of central obesity was reduced
      significantly (p <0.01) in the group receiving additional lifestyle support but
      not in the NHS Health Check only group. CONCLUSIONS: The NHS Health Check service
      in Stoke on Trent resulted in significant reduction in estimated population CVD
      risk. There was no evidence of further benefit of the additional lifestyle
      support services in terms of absolute CVD risk reduction.

PMID- 23116214
TI  - Management of non-healing leg ulcers in Unani system of medicine.
AB  - Non-healing leg ulcers are becoming a major public health problem. The high
      prevalence of leg ulcer directly affects patients' quality of life because it
      produces psychological (anxiety, depression), social and physical (amputation)
      handicap. Most leg ulcers become unsightly and they hardly if ever, yield to
      conventional treatment. Healing of an amputated part may pose a problem, hence
      amputation cannot be recommended without extensive pre-operative investigations.
      Prevalence is high among the poor, for whom expenses of surgery are not
      affordable. Few surgeons try skin graft but unfavourable local condition of the
      ulcer leads to rejection and all efforts prove futile. Keeping all these factors
      in mind, we have tested a Unani formulation for its ulcer healing properties;
      early results were surprising and in some cases unbelievable.

PMID- 23116215
TI  - Antithrombotic activities of aqueous extract from Gardenia jasminoides and its
      main constituent.
AB  - CONTEXT: Gardenia jasminoides J. Ellis (Rubiaceae) is a shrub tree species
      distributed all over the world. Now its pharmacological activities such as anti
      atherosclerosis have been extensively studied. OBJECTIVE: To offer
      pharmacological proof for its further clinical application in cardiovascular
      diseases, the antithrombotic activities of the aqueous extract of G. jasminoides
      (GJ-ext) were studied in mouse and rat models. MATERIALS AND METHODS: GJ-ext was
      administrated orally to detect the effects on the models of carrageenan-induced
      tail thrombosis and arteriovenous shunt thrombosis. The effects of GJ-ext and
      geniposide (p.o.) on antiplatelet aggregation were examined. Geniposide and
      genipin were studied on venous thrombosis by oral administration. RESULTS: GJ-ext
      (67, 133 and 266 mg/kg) and aspirin (50 mg/kg), respectively, decreased the
      length of tail thrombus with average thrombus inhibition rate of 21.9, 55.7, 65.8
      and 57.6% at 48 h and 19.0, 54.5, 69.3 and 56.9% at 72 h after carrageenan
      injection and, meanwhile, improved thrombosis induced by arteriovenous shunt
      (silk thread) with 36.3, 45.5, 86.4 and 63.7% inhibition rate of thrombus
      respectively, and the ED(50) of GJ-ext was 160.8 mg/kg. Furthermore, GJ-ext (67
      mg/kg) and geniposide (20 mg/kg) significantly inhibited platelet aggregation
      induced by thrombin/collagen with 45.1%/19.3% and 52.8%/26.2% aggregation rate.
      Geniposide (10-40 mg/kg) and genipin (5-20 mg/kg) inhibited venous thrombosis
      induced by tight ligation of the inferior vena cava, their ED(50) values were
      18.4 and 8.6 mg/kg, respectively. DISCUSSION AND CONCLUSION: This study indicated
      that GJ-ext and geniposide demonstrated remarkable antithrombotic activities and
      supported their therapeutic uses for thrombotic diseases.

PMID- 23116216
TI  - High genetic diversity and predominance of Rhinovirus A and C from Panamanian
      hospitalized children under five years with respiratory infections.
AB  - BACKGROUND: Human Rhinoviruses (HRVs) have high genetic diversity and three
      species have been described: HRV-A, HRV-B, and the recently recognized HRV-C,
      which has been rapidly identified worldwide. FINDINGS: In the present study, we
      report the frequency and diversity of Human Rhinovirus (HRV) strains circulating
      in Panama from children hospitalized with respiratory infections. CONCLUSIONS:
      HRVs of species A, B and C have been identified with a predominance of HRV-A and
      HRV-C over HRV-B, and marked genetic diversity within each species.

PMID- 23116217
TI  - Membrane-receptor initiated proliferative effects of dienogest in human breast
      cancer cells.
AB  - OBJECTIVES: Dienogest (DNG) is already used in hormone therapy, since recently
      being also the progestogenic component of the first estradiol based contraceptive
      pill. Data on breast cancer risk are currently not available. Progesterone
      receptor membrane component 1 (PGRMC1) is highly expressed in tissues of breast
      cancer patients and has already been proposed as a predictor for breast cancer
      risk. METHODS: MCF-7 cells overexpressing PGRMC1 were stimulated with DNG,
      medroxyprogesterone acetate (MPA), norethisterone (NET) and progesterone (P) as
      well as sequentially and continuously combined with estradiol (E2). RESULTS: DNG
      and MPA alone elicited a significant proliferation at 10-6 and 10-5 M. NET
      increased cell proliferation at all concentrations tested whereas P showed no
      effect. E2 alone elicited a significant increase at 10-10 M, no effect was seen
      at 10-12 M. Addition of the progestins (10-6 M) to E2 at 10-10 M had, compared to
      E2 only, no additional proliferating effect. However, at the low E2
      concentration, DNG, MPA and NET significantly increased the E2-stimulated cell
      proliferation. CONCLUSION: DNG increased proliferation alone and in combination
      with low E2 concentrations. Thus a progestogen-derived breast cancer risk in the
      presence of low E2 concentrations cannot be excluded at least in women
      overexpressing PGRMC1.

PMID- 23116219
TI  - AAP president's address.

PMID- 23116218
TI  - Deletion of interferon-gamma delays onset and severity of dacryoadenitis in
      CD25KO mice.
AB  - INTRODUCTION: To investigate the role of interferon-gamma (IFN-gamma) in the
      onset and severity of dacryoadenitis in the CD25 knockout (KO) mouse model of
      Sjogren Syndrome. METHODS: CD25/IFN-gamma double KO (gammaDKO) mice were created
      by crossbreeding CD25KO and IFN-gammaKO mice. Mice were used at 8, 12, and 16
      weeks. Lacrimal gland (LG) infiltrating lymphocytes were characterized with flow
      cytometry. Tear epidermal growth factor (EGF) concentration was measured with
      enzyme-linked immunosorbent assay (ELISA). Quantitative polymerase chain reaction
      (PCR) evaluated T-cell-related cytokines in LGs. Serum autoantibodies against M3R
      in LG lysates were detected with Western blot. RESULTS: gammaDKO LG showed lower
      lymphocytic infiltration at 8 weeks than in the CD25KO parental strain (~20%
      versus ~60%, respectively), which increased to CD25KO levels at 16 weeks. Flow
      cytometry analysis showed an increase in CD4+ and CD8+ T cells with aging in
      gammaDKO LG, similar to that in CD25KO. gammaDKO had lower levels of interleukin
      (IL)-17A, transforming growth-factor (TGF)-beta1, IL-21, and CCL20, and higher IL
      1beta and IL-13 mRNA transcripts in the LG than in the parental CD25KO strain.
      Autoantibodies to M3R were observed in both strains and significantly increased
      with aging in both strains. CD25KO mice had very low tear EGF concentrations at
      all ages, whereas the ear EGF concentration in gammaDKO mice significantly
      decreased with aging and inversely correlated with the presence of M3R
      autoantibodies and the degree of LG CD4 and CD8+ T-cell infiltration.
      CONCLUSIONS: The deletion of IFN-gamma in the CD25KO mice strain delays glandular
      destruction and preserves glandular function. M3R autoantibodies increased with
      aging in both the gammaDKO and the CD25KO strains. The decrease in LG function in
      gammaDKO correlated with the degree of T-cell infiltration and the presence of
      M3R autoantibodies.

PMID- 23116221
TI  - Variable nornicotine enantiomeric composition caused by nicotine demethylase
      CYP82E4 in tobacco leaf.
AB  - Nornicotine is the demethylation product of nicotine and the precursor of tobacco
      specific nitrosamine N'-nitrosonornicotine (NNN) in tobacco (Nicotiana tabacum
      L.). There is an inconsistent enantiomer fraction (EF) of nornicotine reported in
      the literature. The objective of this study was to explore possible mechanisms to
      account for the variable EF(nnic) in tobacco. A survey of tobacco with different
      demethylating capabilities confirmed that there was variable EF(nnic).
      Experiments of induction and inhibition of the major nicotine demethylase CYP82E4
      activity in tobacco demonstrated that CYP82E4 selectively demethylated (S)
      nicotine and resulted in different EF(nnic) in tobacco leaves. Results from
      plants with silenced demethylases by RNAi suggested that other demethylases
      selectively used (R)-nicotine and resulted in high EF(nnic). In summary,
      enantioselective demethylation likely plays an important role in contributing to
      a large and variable EF(nnic) observed in tobacco.

PMID- 23116220
TI  - Direct renin inhibition prevents cardiac dysfunction in a diabetic mouse model:
      comparison with an angiotensin receptor antagonist and angiotensin-converting
      enzyme inhibitor.
AB  - Hyperglycaemia up-regulates intracellular AngII (angiotensin II) production in
      cardiac myocytes, effects of which are blocked more effectively by renin
      inhibition than ARBs (angiotensin receptor blockers) or ACEis (angiotensin
      converting enzyme inhibitors). In the present study, we determined whether renin
      inhibition is more effective at preventing diabetic cardiomyopathy than an ARB or
      ACEi. Diabetes was induced in adult mice for 10 weeks by STZ (streptozotocin).
      Diabetic mice were treated with insulin, aliskiren (a renin inhibitor),
      benazeprilat (an ACEi) or valsartan (an ARB) via subcutaneous mini-pumps.
      Significant impairment in diastolic and systolic cardiac functions was observed
      in diabetic mice, which was completely prevented by all three RAS (renin
      angiotensin system) inhibitors. Hyperglycaemia significantly increased cardiac
      oxidative stress and circulating inflammatory cytokines, which were blocked by
      aliskiren and benazeprilat, whereas valsartan was partially effective. Diabetes
      increased cardiac PRR (prorenin receptor) expression and nuclear translocation of
      PLZF (promyelocytic zinc finger protein), which was completely prevented by
      aliskiren and valsartan, and partially by benazeprilat. Renin inhibition provided
      similar protection of cardiac function to ARBs and ACEis. Activation of PLZF by
      PRR represented a novel mechanism in diabetic cardiomyopathy. Differential
      effects of the three agents on oxidative stress, cytokines and PRR expression
      suggested subtle differences in their mechanisms of action.

PMID- 23116222
TI  - Stabilization of colloidal suspensions: competing effects of nanoparticle halos
      and depletion mechanism.
AB  - Bimodal colloidal mixtures of nanoparticles and microparticles may show different
      phase behaviors depending upon the interparticle interaction of both species. In
      the present work, we examined the stabilization of spherical microparticles using
      highly charged, spherical nanoparticles. Total internal reflection microscopy
      (TIRM) was used to measure the interaction forces between a charged microparticle
      and flat glass substrate in aqueous solutions at varying volume fractions of
      nanoparticles of the same sign. We found that, in the system containing of highly
      charged nanoparticles, microparticle, and glass substrate, non-adsorbing charged
      nanoparticles in solution did not lead to depletion attraction. Instead, the
      addition of nanoparticles was to consistently create a repulsive force between
      the microparticle and glass substrate even at a very low nanoparticle volume
      fraction. This result might attributed to the formation of thin shells (halos)
      with a high local nanoparticle volume fraction to the region near the glass
      surface, resulting in electrostatic repulsion between the decorated surfaces.
      This study demonstrates that nanoparticle halos can also arise in binary systems
      of mutually but highly repulsive microparticle/nanoparticle dispersions.

PMID- 23116223
TI  - Can stress reduction interventions improve psoriasis? A review.
AB  - Psoriasis remains incurable and many sufferers experience related psychological
      distress and a lower quality of life comparable with other chronic diseases. A
      subpopulation of people with psoriasis believes their condition is exacerbated by
      psychological stress. This review analyses whether stress-reduction interventions
      can reduce: the physical severity of psoriasis and related psychological
      distress. A systematic search across EMBASE, MEDLINE, The Cochrane Library SIGLE
      and PsychInfo, identified 730 trials and 10 were included. Three trials found a
      significant difference in psoriasis outcomes between groups post-intervention, (p
      < 0.05). Seven studies included a psychological outcome and three found a
      significant difference (p < 0.05). Three trials included a quality of life
      measurement and one of these reported a significant improvement (p < 0.001). Due
      to low quality evidence it is currently insufficient to judge stress reduction
      interventions as either effective or ineffective. We make nine recommendations
      for future research in this multidisciplinary field. 

PMID- 23116224
TI  - The effects of temperature and relative humidity on ochratoxin A formation in
      fresh liquorice root.
AB  - In this study, the effects of temperature and relative humidity (RH) on
      ochratoxin A (OTA) formation during liquorice root storage were investigated. For
      this purpose, a real storage procedure in which fresh root was dried in the open
      air was simulated. Four RH-temperature combinations corresponding to average
      climate conditions (RH-temperature) of each season in an important liquorice
      growing and processing region were simulated as follows: A, autumn (T = 15
      degrees C, RH = 49%); B, winter (T = 9 degrees C, RH = 51%); C, spring (T = 22
      degrees C, RH = 35%); and D, summer (T = 29 degrees C, RH = 27%). The crushed
      fresh roots were incubated for 60 days, and the OTA content of the roots was
      determined at 20-day intervals by using inverse ion mobility spectrometry. The
      results showed that the maximum levels of OTA occurred after 40 days and were 4.3
      +/- 1.1, 0.9 +/- 0.2, 7.3 +/- 0.0 and 24.2 +/- 2.5 ngg(-1) in roots stored under
      simulated conditions A, B, C and D, respectively. After 40 days, the amount of
      OTA started to decline in all samples but at different rates. The results seem to
      indicate that temperature plays a more significant role than RH in producing OTA
      by moulds in liquorice root. It appears that 22 degrees C could be considered as
      the critical temperature for OTA formation in liquorice root stored under
      experimental conditions. It could be concluded that liquorice-processing plants
      should obtain, dry and store fresh moist root when the temperature is below the
      critical point. Moreover, the roots stored in the open shade condition should not
      be covered by plastic films even when it is raining as this increases the root
      temperature.

PMID- 23116225
TI  - Olmesartan medoxomil-based antihypertensive therapy evaluated by ambulatory blood
      pressure monitoring: efficacy in high-risk patient subgroups.
AB  - Hypertension affects approximately 26% of the world's adult population and is a
      recognized major risk factor for morbidity and mortality associated with
      cardiovascular, cerebrovascular, and renal diseases. However, despite the
      availability of a range of effective antihypertensive agents and a growing
      awareness of the consequences of high blood pressure (BP), the treatment and
      control of hypertension remains suboptimal. A number of patient subgroups are
      categorized as 'high risk' and may have hypertension that is more difficult to
      treat, including obese individuals, patients with stage 2 hypertension, those
      with type 2 diabetes mellitus (T2DM), patients with coronary artery disease or a
      history of stroke, and Black patients. As the benefits of lowering BP in patients
      with hypertension are unequivocal, particularly in high-risk patients, treating
      high-risk patients with hypertension to BP goals and maintaining 24-hour BP
      control is important to help reduce cardiovascular risk and improve outcomes.
      Although the BP goals recommended in current consensus guidelines for the
      management of patients with hypertension are based on cuff BP measurements,
      ambulatory BP monitoring (ABPM) provides a valuable diagnostic tool and allows a
      more accurate assessment of BP levels throughout the 24-hour dosing period. ABPM
      is a better predictor of prognosis than office BP measurement and is also useful
      for assessing whether antihypertensive therapy remains effective in the critical
      last few hours of the dosing period, which usually coincides with the morning BP
      surge associated with arousal and arising. ABPM has been adopted by new evidence
      based guidelines in the United Kingdom to confirm a suspected diagnosis of
      hypertension, which is an indication of the growing importance of ABPM in the
      management of hypertension. This review provides an overview of the efficacy and
      safety of antihypertensive therapy based on olmesartan medoxomil +/-
      hydrochlorothiazide and amlodipine/olmesartan medoxomil in high-risk patient
      populations enrolled in studies that reported ambulatory BP endpoints. The
      studies identified in this review showed that a titrate-to-BP goal strategy using
      olmesartan medoxomil- or amlodipine/olmesartan medoxomil-based antihypertensive
      therapy was an effective and well-tolerated approach for maintaining BP control
      throughout the full 24-hour dosing period in high-risk patients with difficult-to
      treat hypertension.

PMID- 23116226
TI  - Mechanism of thiolate-disulfide exchange: addition-elimination or effectively
      S(N)2? Effect of a shallow intermediate in gas-phase direct dynamics simulations.
AB  - Direct dynamics trajectory simulations were performed for two examples of the
      thiolate-disulfide exchange reaction, that is, HS(-) + HSSH and CH(3)S(-) +
      CH(3)SSCH(3). The trajectories were computed for the PBE0/6-31+G(d) potential
      energy surface using both classical microcanonical sampling at the ion-dipole
      complex and quasi-classical Boltzmann sampling (T = 300 K) at the central
      transition state. The potential energy surface for these reactions involves a
      hypercoordinate sulfur intermediate. Despite the fact that the intermediate
      resides in a shallow well (less than 5 kcal/mol), very few trajectories follow a
      direct substitution path (the S(N)2 pathway). Rather, the mechanism is addition
      elimination, with several trajectories sampling the intermediate for long times,
      up to 15 ps or longer.

PMID- 23116227
TI  - Synthesis of a targeted biarsenical Cy3-Cy5 affinity probe for super-resolution
      fluorescence imaging.
AB  - Photoswitchable fluorescent probes capable of the targeted labeling of tagged
      proteins are of significant interest due to their ability to enable in situ
      imaging of protein complexes within native biomolecular assemblies. Here we
      describe the synthesis of a fluorescent probe (AsCy3Cy5) and demonstrate the
      targeted labeling and super-resolution imaging of a tagged protein within a
      supramolecular protein complex.

PMID- 23116228
TI  - Gut microbial activity, implications for health and disease: the potential role
      of metabolite analysis.
AB  - Microbial metabolism of proteins and amino acids by human gut bacteria generates
      a variety of compounds including phenol, indole, and sulfur compounds and
      branched chain fatty acids, many of which have been shown to elicit a toxic
      effect on the lumen. Bacterial fermentation of amino acids and proteins occurs
      mainly in the distal colon, a site that is often fraught with symptoms from
      disorders including ulcerative colitis (UC) and colorectal cancer (CRC). In
      contrast to carbohydrate metabolism by the gut microbiota, proteolysis is less
      extensively researched. Many metabolites are low molecular weight, volatile
      compounds. This review will summarize the use of analytical methods to detect and
      identify compounds in order to elucidate the relationship between specific
      dietary proteinaceous substrates, their corresponding metabolites, and
      implications for gastrointestinal health.

PMID- 23116229
TI  - In vitro study of intestinal transport of inorganic and methylated arsenic
      species by Caco-2/HT29-MTX cocultures.
AB  - This study characterizes intestinal absorption of arsenic species using in vitro
      system Caco-2/HT29-MTX cocultures in various proportions (100/0 to 30/70). The
      species assayed were As(V), As(III), monomethylarsonic acid [MMA(V)],
      monomethylarsonous acid [MMA(III)], dimethylarsinic acid [DMA(V)], and
      dimethylarsinous acid [DMA(III)]. The results show that the apparent permeability
      (P(app)) values of pentavalent species increase significantly in the Caco-2/HT29
      MTX cocultures in comparison with the Caco-2 monoculture, probably because of
      enhancement of paracellular transport. For MMA(III) and DMA(III), P(app)
      decreases in the Caco-2/HT29-MTX cell model, and for As(III), there is no change
      in P(app) between the two culture models. Transport studies of arsenic
      solubilized from cooked foods (rice, garlic, and seaweed) after applying an in
      vitro gastrointestinal digestion showed that arsenic absorption also varies with
      the model used, increasing with the incorporation of HT29-MTX in the culture.
      These results show the importance of choosing a suitable in vitro model when
      evaluating intestinal arsenic absorption processes.

PMID- 23116230
TI  - Seminal vesicles of infertile patients with male accessory gland infection:
      ultrasound evaluation after prolonged treatment with tadalafil, a selective
      phosphodiesterase-5 inhibitor.
AB  - The aim of this study was to investigate possible ultrasound seminal vesicle (SV)
      changes in infertile patients with 'hypertrophic-congestive' (HCUF) or 'fibro
      sclerotic' (FSUF) ultrasound form of male accessory gland infection (MAGI) after
      prolonged administration of tadalafil (TAD), a selective phosphodiesterase-5
      inhibitor. Forty infertile patients with HCUF and 40 patients with FSUF and
      erectile dysfunction were selected and arbitrarily divided into two groups, who
      were prescribed TAD 5 mg daily for 3 months, the first 20 consecutive patients
      with HCUF (group A1) or FSUF (group A2) or placebo, the second 20 consecutive
      patients with HCUF (group B1) or FSUF (group B2). All patients underwent scrotal
      and prostate-vesicular transrectal ultrasound evaluation and semen analysis (WHO,
      2010) before and after treatment. Group A1 patients showed a significant
      reduction in fundus/body ratio and higher pre- and post-ejaculatory body SV
      antero-posterior diameter difference compared with the other three groups. These
      patients showed also a significant increase in SV ejection fraction and a
      significant improvement in the total sperm count, progressive motility, seminal
      levels of fructose and ejaculate volume. These results suggest that infertile
      patients with HCUF had an improvement in SV ultrasound features suggestive of
      chronic inflammation after daily treatment with low doses of TAD. 

PMID- 23116231
TI  - Active sulfur cycling by diverse mesophilic and thermophilic microorganisms in
      terrestrial mud volcanoes of Azerbaijan.
AB  - Terrestrial mud volcanoes (TMVs) represent geochemically diverse habitats with
      varying sulfur sources and yet sulfur cycling in these environments remains
      largely unexplored. Here we characterized the sulfur-metabolizing microorganisms
      and activity in four TMVs in Azerbaijan. A combination of geochemical analyses,
      biological rate measurements and molecular diversity surveys (targeting metabolic
      genes aprA and dsrA and SSU ribosomal RNA) supported the presence of active
      sulfur-oxidizing and sulfate-reducing guilds in all four TMVs across a range of
      physiochemical conditions, with diversity of these guilds being unique to each
      TMV. The TMVs varied in potential sulfate reduction rates (SRR) by up to four
      orders of magnitude with highest SRR observed in sediments where in situ sulfate
      concentrations were highest. Maximum temperatures at which SRR were measured was
      60 degrees C in two TMVs. Corresponding with these trends in SRR, members of the
      potentially thermophilic, spore-forming, Desulfotomaculum were detected in these
      TMVs by targeted 16S rRNA analysis. Additional sulfate-reducing bacterial
      lineages included members of the Desulfobacteraceae and Desulfobulbaceae detected
      by aprA and dsrA analyses and likely contributing to the mesophilic SRR measured.
      Phylotypes affiliated with sulfide-oxidizing Gamma- and Betaproteobacteria were
      abundant in aprA libraries from low sulfate TMVs, while the highest sulfate TMV
      harboured 16S rRNA phylotypes associated with sulfur-oxidizing
      Epsilonproteobacteria. Altogether, the biogeochemical and microbiological data
      indicate these unique terrestrial habitats support diverse active sulfur-cycling
      microorganisms reflecting the in situ geochemical environment.

PMID- 23116232
TI  - Defect-engineered three-dimensional graphene-nanotube-palladium nanostructures
      with ultrahigh capacitance.
AB  - The development of three-dimensional carbon-based nanostructures is the next step
      forward for boosting industrial applications of carbon nanomaterials such as
      graphenes and carbon nanotubes. Some defects, which have been considered as
      detrimental factors for maintaining exceptional materials properties of two
      dimensional graphene, can be actively used to synthesize three-dimensional
      graphene-based carbon nanostructures. Here we describe a fast and heretofore
      unreported defect-engineered method to synthesize three-dimensional carbon
      nanohybrid structures with strong bonding between graphene nanoplatelets and
      carbon nanotubes using simple microwave irradiation and an ionic liquid. Our one
      pot method utilizes defect-engineered sequential processes: microwave-based
      defect generation on graphene nanoplatelets, anchoring of palladium nanoparticles
      on these defects, and subsequent growth of carbon nanotubes by use of an ionic
      liquid. The unique three-dimensional nanostructures showed an ultrahigh redox
      capacitance due to high porosity, a high surface-to-volume ratio from the spacer
      role of vertically standing one-dimensional carbon nanotubes on graphene sheets,
      and capacitance-like redox response of the palladium nanoparticles. The proposed
      defect-engineered method could lead to novel routes to synthesizing three
      dimensional graphene-based nanostructures with exceptionally high performance in
      energy storage systems.

PMID- 23116233
TI  - Reply to comment on Fisichella et al. (2012), "Intestinal toxicity evaluation of
      TiO2 degraded surface-treated nanoparticles: a combined physico-chemical and
      toxicogenomics approach in Caco-2 cells" by Faust et al.
AB  - In this response, we discuss the major differences that clearly distinguish our
      results from those mentioned by Faust et al. In particular, the experiments have
      been conducted on nanoparticles of different nature, what mainly explains the
      observed discrepancies.

PMID- 23116234
TI  - A novel rodent model of spinal metastasis and spinal cord compression.
AB  - BACKGROUND: Spinal cord metastatic lesions affect a high number of cancer
      patients usually resulting in spinal cord compression syndrome. A major obstacle
      in the research of spinal metastatic disease is the lack of a simple reproducible
      animal model that mimics the natural course of the disease. In this study, we
      present a highly reproducible rodent model that can be used for different types
      of cancers while mimicking the natural course of human metastatic spinal cord
      compression syndrome. RESULTS: All sixteen Fisher 344 rats survived the dorsal
      approach intraosseous implantation of CRL-1666 adenocarcinoma cells and both rats
      survived the sham control surgery. By Day 13 functional analysis via the modified
      Basso-Beattie-Bresnahan (BBB) locomotor rating scale showed significant decrease
      in motor function; median functional score was 3 for the tumor group (p =
      0.0011). Median time to paresis was 8.7 days post-operatively. MR imaging
      illustrated repeated and consistent tumor formation, furthermore, onset of
      neurological sequale was the result of tumor formation and cord compression as
      confirmed by histological examination. CONCLUSIONS: Analysis of these findings
      demonstrates a repeatable and consistent tumor growth model for cancer spinal
      metastases in rats. This novel rat model requires a less intricate surgical
      procedure, and as a result minimizes procedure time while subsequently increasing
      consistency. Therefore, this model allows for the preclinical evaluation of
      therapeutics for spinal metastases that more closely replicates physiological
      findings.

PMID- 23116235
TI  - How patients with multiple sclerosis perceive cognitive slowing.
AB  - Slowed processing speed is the primary cognitive deficit in multiple sclerosis
      (MS). However, no studies have examined how patients perceive this deficit. The
      purpose of this paper is to examine perceived processing speed difficulties in
      clinical and community samples of MS patients. As expected, MS patients reported
      more processing speed difficulties than controls. Perceived processing speed
      difficulties were significantly associated with impulsivity, slowed motor speed,
      greater anxiety, and increased introversion. In contrast, perceived processing
      speed did not correlate well with objective measures of processing speed.
      Findings showed that MS patients perceive their thinking to be significantly
      slowed. Perceived cognitive slowing was most related to performance on motor
      tasks and elevated anxiety. Evaluation of anxiety and patient education about
      objective measures versus subjective perceptions of slowed processing speed may
      be helpful to MS patients who report significant cognitive slowing.

PMID- 23116236
TI  - Salt-induced control of supramolecular order in biocatalytic hydrogelation.
AB  - Biocatalytic action and specific ion effects are both known to have dramatic
      effects on molecular self-assembly and hydrogelation. In this paper, we
      demonstrate that these effects are highly cooperative. Biocatalytic hydrogelation
      of Fmoc peptides in the presence of salts combines kinetic (through enzymatic
      catalysis) and thermodynamic (specific ion and protein templating) contributions
      when applied in combination. Spectroscopic data (obtained by fluorescence
      spectroscopy and circular dichroism) revealed that hydrophobic interactions are
      greatly affected, giving rise to differential chiral organization and
      supramolecular structure formation. The kinetic effects of catalytic action could
      be removed from the system by applying a heat/cool cycle, giving insight into the
      thermodynamic influence of both protein and salt on these systems and showing
      that the effects of catalysis, templating, and salts are cooperative. The
      variable molecular interactions are expressed as variable material properties,
      such as thermal stability and mechanical strength of the final gel-phase
      material. To gain more insight into the role of the enzyme, beyond catalysis, in
      the underlying mechanism, static light scattering is performed, which indicates
      the different mode of aggregation of the enzyme molecules in the presence of
      different salts in aqueous solution that may play a role to direct the assembly
      via templating. Overall, the results show that the combination of specific salts
      and enzymatic hydrogelation can give rise to complex self-assembly behaviors that
      may be exploited to tune hydrogel properties.

PMID- 23116237
TI  - Coagulation and fibrynolitic parameters in women and the effects of hormone
      therapy; comparison of transdermal and oral administration.
AB  - It is established that hormone therapy (HT) is related with significant increased
      prothrombotic risk factor. The aim of our study was to assess the effects of oral
      hormone therapy (o-HT) and transdermal hormone therapy (t-HT) on hemostasis
      parameters: fibrinogen (Fg) concentration, the maximum velocity of polymerization
      of clot formation, fibrin half-time lysis, plasma level of thrombin inhibitor of
      fibrinolysis (TAFI) and activity of generated thrombin and plasmin amidolytic
      activity. We observed that values of initial velocity of polymerization in o-HT
      group were increased (94.64 mOD/min vs. 131.50 mOD/min, p < 0.001) compared to
      control group. Fibrin lysis half-time increased in both groups with HT (controls 
      18.26 min vs. 32.43 min (o-HT); 23.34 min transdermal hormone therapy (t-HT) p <
      0.001) compared to controls. The activity of thrombin was statistically higher in
      plasma of women after o-HT (72.6 +/- 8.5 mOD/min) than in patients with t-HT
      (53.7 +/- 10.1 mOD/min) and controls (51.2 +/- 10 mOD/min. Plasmin activity was
      the highest in controls (84.5 +/- 10.2 mOD/min). The highest level of TAFI we
      observed in patients after oral hormones (80.38 +/- 8.23%); women on transdermal
      HT had 61.58 +/- 9.81% and the lowest concentration of TAFI we noted in controls
      44.70 +/- 10.16). The results of our study show that HT may partly explain the
      increase in venous thrombosis (VTE) and cardiovascular events reported after the
      use of it, especially the oral form of treatment.

PMID- 23116238
TI  - Men's and women's exposure and perpetration of partner violence: an
      epidemiological study from Sweden.
AB  - BACKGROUND: Over the past 30 years, intimate partner violence (IPV) against women
      and its health consequences has become a well established research area and is
      recognized worldwide as a significant public health issue. Studies on IPV
      directed at men are less explored, however recently women's use of IPV and men's
      victimization is gaining growing attention. Earlier population-based studies
      performed in Sweden have primarily investigated men's violence against women,
      while women's use of violence and men's exposure as well as the existence of
      controlling behaviours have been neglected research areas This explorative study
      investigated the exposure to and perpetration of intimate partner violence, the
      use of control behaviours and the associated risk factors among a sample of
      Swedish men and women. METHODS: This cross-sectional population-based study
      included 173 men and 251 women of age 18-65 randomly selected among the Swedish
      population. A questionnaire based on the revised Conflicts Tactics Scale (CTS2)
      and the subscale 'isolating control' from the Controlling Behaviour Scale (CBS)
      was used to collect data on violence exposure and perpetration. Regression
      analyses were used for risk factor assessment. RESULTS: More men (11%) than women
      (8%) reported exposure to physical assault in the past year, while more women
      reported exposure to sexual coercion. Duration of present relationship <= 3 years
      was identified as a significant risk factor for men's exposure. Young age, lack
      of social support and being single, constituted risk factors for women's
      exposure. Surprisingly many men (37%) and women (41%) also reported exposure to
      controlling behaviours. CONCLUSIONS: In partner violence research, both men's and
      women's exposure should be explored however findings need to be interpreted with
      caution. This first study in a Swedish sample establishes the basis for future
      investigations on partner violence and coercive control tactics.

PMID- 23116239
TI  - Ovine forestomach matrix biomaterial is a broad spectrum inhibitor of matrix
      metalloproteinases and neutrophil elastase.
AB  - Proteases play a critical role in the ordered remodelling of extracellular matrix
      (ECM) components during wound healing and tissue regeneration. However, the
      usually ordered proteolysis is compromised in chronic wounds due to over
      expression and high concentrations of matrix metalloproteinase's (MMPs) and
      neutrophil elastase (NE). Ovine forestomach matrix (OFM) is a decellularised
      extracellular matrix-based biomaterial developed for tissue regeneration
      applications, including the treatment of chronic wounds, and is a heterogeneous
      mixture of ECM proteins and proteoglycans that retains the native structural and
      functional characteristics of tissue ECM. Given the diverse molecular species
      present in OFM, we hypothesised that OFM may contain components or fragments that
      inhibit MMP and NE activity. An extract of OFM was shown to be a potent inhibitor
      of a range of tissue MMPs (IC50 s = 23 +/- 5 to 115 +/- 14 ug/ml) and NE (IC50 =
      157 +/- 37 ug/ml), and was more potent than extracts prepared from a known
      protease modulating wound dressing. The broad spectrum activity of OFM against
      different classes of MMPs (i.e. collagenases, gelatinases and stromelysins) may
      provide a clinical advantage by more effectively addressing the protease
      imbalance seen in chronic wounds.

PMID- 23116240
TI  - Differences on adolescent life goal profile scale between a clinical and non
      clinical adolescent sample.
AB  - OBJECTIVE: This study aimed to determine similarities and differences on
      perceived importance and perceived attainability of life goals between a clinical
      and non-clinical adolescent sample. METHOD: 244 students and 54 adolescent
      patients completed the Adolescent Life Goal Profile Scale (ALGPS). The ALGPS
      measures perceived importance and perceived attainability of four main life goal
      categories: Relations, Generativity, Religion, and Achievements. As a control, we
      used five measures of mental health, quality of life, and personality. RESULTS:
      There were no differences on perceived importance on the Generativity, Religion,
      and Achievement life goal factor, but patients perceived relation-oriented goals
      less important than non-patients. Perceived attainability of life goals factors
      was lower for patients on all life goals except for Generativity. Compared to non
      patients, patients were less happy and satisfied and had lower sense of coherence
      and self-efficacy. Patients were also less emotionally stable, had lower
      conscientiousness, but higher intellect. CONCLUSIONS: Though patients appear less
      content with life in general than non-patients, chances are that they uphold
      their concern and care for others, remain devoted in their religious stand, and
      stay committed to their achievement-related goals. The lower perceived importance
      of relations within the patient group should be awarded clinical attention.

PMID- 23116241
TI  - The relationship between obesity and health-related quality of life in Chinese
      patients with schizophrenia.
AB  - OBJECTIVE: Studies have reported that up to 60% of individuals with schizophrenia
      are overweight or obese. This study explored the relationship between obesity and
      health-related quality of life (HRQoL) in Chinese patients with schizophrenia.
      METHODS: A total of 1,108 patients with schizophrenia aged 18-50 years were
      recruited from 10 different sites in China. Demographic and medical information
      were collected; the Mandarin version of Short Form 36 Health Survey questionnaire
      (SF-36) was used to assess HRQoL; in addition,height and weight were measured to
      calculate body mass index (BMI). BMI was categorized into underweight, normal
      weight, overweight and obese using cutoffs for Asian populations recommended by
      the World Health Organization. RESULTS: Fifty-six percent of participants with
      schizophrenia were overweight or obese. A higher BMI was associated with
      significantly lower scores in physical functioning, role-physical, and physical
      component summary (p's <= 0.010). Obese patients with schizophrenia had
      significantly lower scores in 3 domains and physical component summary of the SF
      36 compared with normal weight patients (p's <= 0.007). CONCLUSION: Obesity is
      associated with decreased HRQoL in Chinese patients with schizophrenia. Our
      findings suggest that the prevention and management of weight gain and obesity is
      important in improving HRQoL in patients who suffer from this devastating mental
      illness.

PMID- 23116242
TI  - Deep brain stimulation - effects on swallowing function in Parkinson's disease.
AB  - OBJECTIVE: In patients with Parkinson's disease (PD), deep brain stimulation of
      the subthalamic nucleus (STN DBS) is well recognized in improving limb function,
      but the outcome on swallowing function has rarely been studied. The aim of this
      work was to evaluate the effect of STN DBS on pharyngeal swallowing function in
      patients with PD using self-estimation and fiberoptic endoscopic evaluation of
      swallowing. METHODS: Eleven patients (aged 41-72, median 61 years) were evaluated
      preoperatively and at 6 and 12 months after STN DBS surgery. All patients were
      evaluated with self-estimation on a visual analogue scale, and eight of them with
      a fiberoptic endoscopic examination with a predefined swallowing protocol
      including Rosenbek's Penetration-Aspiration Scale, Secretion Severity Scale,
      preswallow spillage, pharyngeal residue, and pharyngeal clearance. RESULTS: The
      self-assessments of swallowing function revealed a subjective improvement with
      STN DBS stimulation, whereas the data from the swallowing protocol did not show
      any significant effect of the STN DBS treatment itself. The prevalence of
      aspiration was not affected by the surgery. CONCLUSIONS: The results show that
      swallowing function was not negatively affected by STN DBS and the risk of
      aspiration did not increase. Self-estimation of swallowing function showed a
      subjective improvement due to stimulation.

PMID- 23116243
TI  - River islands, refugia and genetic structuring in the endemic brown frog Rana
      kukunoris (Anura, Ranidae) of the Qinghai-Tibetan Plateau.
AB  - Frequently, Pleistocene climatic cycling has been found to be the diver of
      genetic structuring in populations, even in areas that did not have continental
      ice sheets, such as on the Qinghai-Tibetan Plateau (QTP). Typically, species
      distributed on the plateau have been hypothesized to re-treat to south-eastern
      refugia, especially during the Last Glacial Maximum (LGM). We evaluated sequence
      variation in the mitochondrial DNA gene Cytb and the nuclear DNA gene RAG-1 in
      Rana kukunoris, a species endemic to the QTP. Two major lineages, N and S, were
      identified, and lineage N was further subdivided into N1 and N2. The geographical
      distribution and genealogical divergences supported the hypothesis of multiple
      refugia. However, major lineages and sublineages diverged prior to the LGM.
      Demographical expansion was detected only in lineage S and sublineage N2.
      Sublineage N1 might have survived several glacial cycles in situ and did not
      expand after the LGM because of the absence of suitable habitat; it survived in
      river islands. Genetic analysis and environment modelling suggested that the
      north-eastern edge of QTP contained a major refugium for R. kukunoris. From here,
      lineage S dispersed southwards after the LGM. Two microrefugia in northern Qilian
      Mountains greatly contributed to current level of intraspecific genetic
      diversity. These results were found to have important implications for the
      habitat conservation in Northwest China.

PMID- 23116244
TI  - Effect of curcumin on dexamethasone-induced testicular toxicity in mice.
AB  - CONTEXT: Curcumin is a yellow-orange polyphenol derived from turmeric [Curcuma
      longa L. (Zingiberaceaerhizomes)]. Turmeric is a main ingredient of Indian,
      Persian, and Thai dishes. Extensive studies within the last half a century have
      demonstrated the protective action of curcumin in many disorders of the body.
      OBJECTIVE: This study evaluated the protective effect of curcumin on
      dexamethasone-induced spermatogenesis defects in mice. MATERIALS AND METHODS:
      Thirty-two NMRI mice were randomly divided into 4 groups. The first (control)
      group received 1 mL/day of distilled water by intraperitoneal (i.p.) injection
      for 7 days. The second group received 200 mg/kg/day of curcumin (Cur) for 10
      days. Third group received 7 mg/kg/day of dexamethasone (Dex) for 7 days. Forth
      group received 200 mg/kg of curcumin for 10 days after dexamethasone treatment.
      Testicular histopathology, morphometric analysis, head sperm counting, and
      immunohistochemistry assessments were performed for evaluation of the
      dexamethasone and curcumin effects. RESULTS: Expression of Bcl-2 was
      significantly increased in the curcumin + dexamethasone group compared with
      dexamethasone-treated animals (p < 0.05). Dexamethasone induced spermatogenesis
      defects including epithelial vacuolizations, sloughing of germ cells, reduction
      of seminiferous tubule diameter, reduction in the number of sperm heads and
      significant maturation arrest (p < 0.001). Curcumin + dexamethasone treatment
      significantly prevented these changes (p < 0.05). DISCUSSION AND CONCLUSION: The
      results of this study demonstrate that curcumin increases the expression of Bcl-2
      protein, an important anti-apoptotic factor, and improves the spermatogenesis
      defects in dexamethasone treated mice. Curcumin has a potent protective effect
      against the testicular toxicity and might be clinically useful.

PMID- 23116245
TI  - The first line of defense against cardiac hypertrophy.
AB  - The embryonic phenotype transformation of cardiomyocytes is an important
      characteristic of pathological cardiac hypertrophy. It includes transcriptional
      reprogramming of gene expression, a switch from lipid metabolism to carbohydrate
      metabolism, and a shift from alpha-myosin heavy chain (MHC) to fetal beta-MHC
      expression. The embryonic and adult cardiacmyocytes have distinct gene expression
      profiles. A series of genes that are expressed in embryos are later shut down
      after birth through the inhibition of endogenous constitutively activated
      molecules. These genes can be reactivated if these inhibitors are inactivated or
      down regulated, as occurs under certain pathological conditions. This promotes
      pathological cardiac hypertrophy. In this review, we list a class of endogenous
      molecules whose expression is inactivated during cardiac hypertrophy. They play a
      positive role in inhibition of the occurrence and development of cardiac
      hypertrophy and constitute the first natural line of defense against pathological
      cardiac hypertrophy.

PMID- 23116246
TI  - Development of aptamer-based nanomaterials for biological analysis.
AB  - Aptamers selected from a large random sequence pool are oligonucleic acid or
      peptide molecules that bind to a specific target molecule with high affinity and
      sensitivity. Targets range from small molecules to proteins and peptides, even
      tissue or cells. As such, aptamers have captured the attention of scientists
      actively developing technologies for diverse biomedical applications.
      Particularly, when functionalized with nanomaterials, aptamers offer properties
      for both biomedical and bioanalytical applications. In this review, these
      features and properties are discussed with particular emphasis on the use of
      aptamer-based biosensor/detection platforms.

PMID- 23116247
TI  - Simultaneous determination of masked deoxynivalenol and some important type B
      trichothecenes in Chinese corn kernels and corn-based products by ultra
      performance liquid chromatography-tandem mass spectrometry.
AB  - A total of 969 corn kernels and corn-based products collected from 24 provinces
      in China between 2008 and 2011 were analyzed for deoxynivalenol, deoxynivalenol 3
      glucoside, 3-acetyl-deoxynivalenol, and 15-acetyl-deoxynivalenol by
      ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).
      Deoxynivalenol was the predominant mycotoxin detected. A total of 29 out of 969
      samples (corn kernels: 9/289, mean = 1884 MUg/kg; corn-based products: 20/680,
      mean = 1580 MUg/kg) contain deoxynivalenol at the levels exceeding the Chinese
      regulatory limit of 1000 MUg/kg for deoxynivalenol in corn. The average relative
      concentration ratios (%) for deoxynivalenol 3-glucoside/deoxynivalenol for all
      four years were 25% +/- 5% in corn kernels and 34% +/- 4% in corn-based products.
      The results of this study indicate that it is necessary to include deoxynivalenol
      3-glucoside in both risk assessment of deoxynivalenol and its derivatives and
      development of the tolerance limit for deoxynivalenol in Chinese corn kernels and
      corn-based products.

PMID- 23116248
TI  - Y27, a novel derivative of 4-hydroxyquinoline-3-formamide, prevents the
      development of murine systemic lupus erythematosus-like diseases in MRL/lpr
      autoimmune mice and BDF1 hybrid mice.
AB  - INTRODUCTION: Naturally occurring CD4+CD25+ regulatory T (Treg) cells are central
      to the maintenance of peripheral tolerance. Impaired activity and/or a lower
      frequency of these cells lead to systemic lupus erythematosus (SLE). Manipulating
      the number or activity of Treg cells is to be a promising strategy in treating it
      and other autoimmune diseases. We have examined the effects of Y27, a novel
      derivative of 4-hydroxyquinoline-3-formamide, on SLE-like symptoms in MRL/lpr
      autoimmune mice and BDF1 hybrid mice. Whether the beneficial effect of Y27
      involves modulation of CD4+CD25+ Treg cells has also been investigated. METHODS:
      Female MRL/lpr mice that spontaneously develop lupus were treated orally by
      gavage with Y27 for 10 weeks, starting at 10 weeks of age. BDF1 mice developed a
      chronic graft-versus-host disease (GVHD) by two weekly intravenous injections of
      parental female DBA/2 splenic lymphocytes, characterized by immunocomplex
      mediated glomerulonephritis resembling SLE. Y27 was administered to chronic GVHD
      mice for 12 weeks. Nephritic symptoms were monitored and the percentage of
      CD4+CD25+FoxP3+ Treg peripheral blood leukocyte was detected with mouse
      regulatory T cell staining kit by flowcytometry. Purified CD4+CD25+ Tregs were
      assessed for immune suppressive activity using the mixed lymphocyte reaction.
      RESULTS: The life-span of MRL/lpr mice treated with Y27 for 10 weeks was
      significantly prolonged, proteinuria and renal lesion severity were ameliorated,
      and blood urea nitrogen, triglyceride and serum anti-double-stranded DNA
      antibodies were decreased. Similar results were found in chronic GVHD mice.
      Administration of Y27 had little impact on percentage of the peripheral blood
      lymphocyte CD4+CD25+Foxp3+ Treg cells in both groups of mice. In contrast, the
      suppressive capacity of CD4+CD25+ Treg cells in splenocytes was markedly
      augmented in Y27-treated mice ex vivo. CONCLUSIONS: Experimental evidence of the
      protect effects of Y27 against autoimmune nephritis has been shown. The mechanism
      may involve enhancement of the suppressive capacity of CD4+CD25+ Treg cells.

PMID- 23116249
TI  - The importance of being aromatic: pi interactions in sodium symporters.
AB  - In the LeuT family of sodium solute symporters, 13-17% of the residues in
      transmembrane domains are aromatic. The unique properties of aromatic amino acids
      allow them to play specialized roles in proteins, but their function in membrane
      transporters is underappreciated. Here we analyze the pi bonding pattern in the
      LeuT (5TMIR) family and then describe the role of a triad of aromatic residues in
      sodium-dependent sugar cotransporters (SGLTs). In SLC5 symporters, three aromatic
      residues in TM6 (SGLT1 W289, Y290, and W291) are conserved in only those
      transporting sugars and inositols. We used biophysical analysis of mutants to
      discover their functional roles, which we have interpreted in terms of CH-pi, pi
      pi, and cation-pi bonding. We discovered that (1) glucose binding involves CH-pi
      stacking with Y290, (2) pi T-stacking interactions between Y290 and W291 and H
      bonding between Y290 and N78 (TM1) are essential to form the sodium and sugar
      binding sites, (3) the Na(+):sugar stoichiometry is determined by these residues,
      and (4) W289 may be important in stabilizing the structure through H-bonding to
      TM3. We also find that the WYW triad plays a role in Na(+) coordination at the
      Na1 site, possibly through cation-pi interactions. Surprisingly, this Na(+) is
      not necessarily coupled to glucose translocation. Our analysis of pi interactions
      in other LeuT proteins suggests that they also contribute to the structure and
      function in this whole family of transporters.

PMID- 23116250
TI  - Vemurafenib: targeted inhibition of mutated BRAF for treatment of advanced
      melanoma and its potential in other malignancies.
AB  - Vemurafenib is the first molecularly targeted therapy to be licensed in the US
      and Europe for treatment of advanced melanoma. Its mechanism of action involves
      selective inhibition of the mutated BRAF V600E kinase that leads to reduced
      signalling through the aberrant mitogen-activated protein kinase (MAPK) pathway.
      Its efficacy is restricted to melanomas carrying the BRAF V600E mutation, which
      is seen in approximately 50% of all melanomas. In a randomized phase III trial,
      it was superior to dacarbazine in first-line treatment of advanced melanoma, with
      an overall response rate (ORR) of 48% (95% CI 42, 45), an estimated 6-month
      progression-free survival (PFS) of 5.3 versus 1.6 months (hazard ratio [HR] 0.26;
      95% CI 0.20, 0.33; p < 0.001) and a statistically superior 12-month overall
      survival (OS) rate of 55% versus 43% (HR 0.62 [95% CI 0.49, 0.77]). Vemurafenib
      is generally well tolerated, but its use can be associated with development of
      cutaneous neoplasms such as squamous cell carcinoma (SCC) and keratoacanthoma
      (KA). These lesions can be excised safely without the need for withholding the
      drug or reducing its dose. Mechanisms of resistance to vemurafenib do not involve
      development of secondary mutations in the BRAF kinase domain, but may be related
      to BRAF V600E over-amplification, bypassing mechanisms via upregulation and
      overexpression of other components in the MAPK signalling cascade or activation
      of alternative pathways with potential to enhance cell growth, proliferation and
      survival. Clinical trials to test the efficacy of vemurafenib in combination with
      immunomodulatory agents, such as ipilimumab, and MAPK kinase (MEK) inhibitors,
      such as GDC-0973, in the treatment of advanced melanoma are currently underway.
      Also under investigation is the use of vemurafenib in other solid tumours with
      BRAF mutations, such as papillary thyroid cancer.

PMID- 23116252
TI  - US Food and Drug Administration's Risk Evaluation and Mitigation Strategy for
      extended-release and long-acting opioids: pros and cons, and a European
      perspective.
AB  - Prescriptions for opioid analgesics to manage moderate-to-severe chronic non
      cancer pain have increased markedly over the last decade. An unintentional
      consequence of greater prescription opioid utilization has been the parallel
      increase in misuse, abuse and overdose, which are serious risks associated with
      all opioid analgesics. In response to disturbing rises in prescription opioid
      abuse, the US Food and Drug Administration (FDA) has proposed the implementation
      of aggressive Risk Evaluation and Mitigation Strategies (REMS). While REMS could
      dramatically change the development, release, marketing and prescription of
      extended-release opioids, questions remain on how these programmes may influence
      prescribing practices, patient safety and ultimately patient access to these
      agents. The extent of the availability and misuse of prescription opioids in
      Europe is difficult to assess from the data currently available, due in large
      part to the considerable differences in prescribing patterns and regulations
      between countries. Balancing the availability of prescription opioids for those
      patients who have pain, while discouraging illicit use, is a complex challenge
      and requires effective efforts on many levels, particularly in Europe where
      policies are quite different between countries.

PMID- 23116254
TI  - Nuclear magnetic shielding for hydrogen in selected isolated molecules.
AB  - We present the results of gas-phase NMR measurements designed to yield a new
      experimental value for the absolute (1)H magnetic shielding for an isolated
      hydrogen molecule and its deuterium isotopomers. The results are based on the
      original method of direct shielding measurements (Jackowski et al., 2010) and the
      density dependence of (1)H, (2)H, and (3)He NMR frequencies for molecular
      hydrogen and atomic helium-3. The absolute isotropic magnetic shielding measured
      for molecular hydrogen, sigma(0)(H(2)), is 26.293(5) ppm at 300 K, within
      experimental error of previous measurements based on spin-rotation data and
      quantum chemistry computations, 26.289(2) ppm (Sundholm and Gauss, 1997), and
      recent ab initio calculations. We also report isotope effects in shielding for
      H(2), HD, and D(2) molecules that are consistent with theoretical predictions. In
      addition, gas-phase (1)H chemical shifts extrapolated to zero density have been
      measured for numerous small molecules. Our results yield precise absolute
      shielding data that will be useful in establishing benchmark computational
      chemistry methods for calculating rovibrational averaged magnetic shielding.

PMID- 23116253
TI  - Pregnancy outcomes and factors associated with voluntary pregnancy termination in
      women who had been treated for acne with isotretinoin.
AB  - OBJECTIVE: We aimed to study the pregnancy outcomes of women exposed to
      isotretinoin and to identify the factors influencing their decision to request an
      abortion. METHODS: The study prospectively identified 79 women who had been
      treated for acne with isotretinoin during the periconceptional period, and who
      were followed up until completion of their pregnancy. Characteristics of exposure
      and doses were self-reported by participants. RESULTS: Of the 56 participants who
      decided to continue their pregnancy, there were 11 spontaneous abortions and 44
      women who delivered healthy full-term babies of which 19 had been exposed to
      isotretinoin <1 month before conception or during pregnancy. In a nominal
      logistic regression analysis including 68 patients who provided adequate
      information for analysis, exposure to isotretinoin >2 weeks post-conception and
      pregnancy termination recommended by the first-contact physician were found to be
      significantly associated with patients' decision to undergo elective abortion:
      adjusted OR = 9.87 (95% CI 1.18-82.34) and 12.51 (95% CI 2.36-66.29),
      respectively. CONCLUSIONS: Our study reports an elevated rate of babies born
      without evidence of gross malformation or neurofunctional abnormality even tough
      exposure occurred during the teratogenic risk period. However, caution is
      recommended since a substantial risk of congenital malformations has been
      reported with low doses of isotretinoin and at exposures limited to early
      pregnancy. We also found that primary-care physicians may influence patients'
      decision to request pregnancy termination independently of their timing of
      exposure to isotretinoin.

PMID- 23116251
TI  - Advances in drug development for acute migraine.
AB  - Triptans revolutionized medical recognition and the acute treatment of migraine.
      Yet, throughout a lifetime, millions of patients who live with migraine endure
      hundreds of days of disability due to their disease. Most migraine attacks
      respond to migraine-specific interventions, but attack response does not predict
      patient response. Generally, migraine patients respond to acute treatment for
      some, but not necessarily all, attacks of migraine. Consequently, there remains a
      substantial unmet clinical need for better acute treatment of migraine. Numerous
      avenues of research and clinical observation provide insight into potential
      advances in acute treatment of migraine. These include better delivery systems
      for existing drugs, as well as the development of potential new therapeutic
      agents. In addition, new changes in migraine taxonomy and clinical observations
      of migraine suggest additional important therapeutic opportunities. Based on
      clinical observations, this article explores future acute treatment needs, drugs
      in development for acute migraine, and new products that deliver established
      drugs to improve treatment response.

PMID- 23116255
TI  - Storage conditions for stability of offline measurement of fractional exhaled
      nitric oxide after collection for epidemiologic research.
AB  - BACKGROUND: The measurement of fractional concentration of nitric oxide in
      exhaled air (FeNO) is valuable for the assessment of airway inflammation. Offline
      measurement of FeNO has been used in some epidemiologic studies. However, the
      time course of the changes in FeNO after collection has not been fully clarified.
      In this study, the effects of storage conditions on the stability of FeNO
      measurement in exhaled air after collection for epidemiologic research were
      examined. METHODS: Exhaled air samples were collected from 48 healthy adults
      (mean age 43.4 +/- 12.1 years) in Mylar bags. FeNO levels in the bags were
      measured immediately after collection. The bags were then stored at 4 degrees C
      or room temperature to measure FeNO levels repeatedly for up to 168 hours.
      RESULTS: In the bags stored at room temperature after collection, FeNO levels
      were stable for 9 hours, but increased starting at 24 hours. FeNO levels remained
      stable for a long time at 4 degrees C, and they were 99.7% +/- 7.7% and 101.3% +/
      15.0% relative to the baseline values at 24 and 96 hours, respectively. When the
      samples were stored at 4 degrees C, FeNO levels gradually decreased with time
      among the subjects with FeNO >= 51 ppb immediately after collection, although
      there were almost no changes among the other subjects. FeNO levels among current
      smokers increased even at 4 degrees C, although the values among ex-smokers
      decreased gradually, and those among nonsmokers remained stable. The rate of
      increase was significantly higher among current smokers than among nonsmokers and
      ex-smokers from 9 hours after collection onwards. CONCLUSIONS: Storage at 4
      degrees C could prolong the stability of FeNO levels after collection. This
      result suggests that valid measurements can be performed within several days if
      the samples are stored at 4 degrees C. However, the time course of the changes in
      FeNO levels differed in relation to initial FeNO values and cigarette smoking.

PMID- 23116256
TI  - Cutaneous nociceptors lack sensitisation, but reveal MU-opioid receptor-mediated
      reduction in excitability to mechanical stimulation in neuropathy.
AB  - BACKGROUND: Peripheral nerve injuries often trigger a hypersensitivity to tactile
      stimulation. Behavioural studies demonstrated efficient and side effect-free
      analgesia mediated by opioid receptors on peripheral sensory neurons. However,
      mechanistic approaches addressing such opioid properties in painful neuropathies
      are lacking. Here we investigated whether opioids can directly inhibit primary
      afferent neuron transmission of mechanical stimuli in neuropathy. We analysed the
      mechanical thresholds, the firing rates and response latencies of sensory fibres
      to mechanical stimulation of their cutaneous receptive fields. RESULTS: Two weeks
      following a chronic constriction injury of the saphenous nerve, mice developed a
      profound mechanical hypersensitivity in the paw innervated by the damaged nerve.
      Using an in vitro skin-nerve preparation we found no changes in the mechanical
      thresholds and latencies of sensory fibres from injured nerves. The firing rates
      to mechanical stimulation were unchanged or reduced following injury.
      Importantly, MU-opioid receptor agonist [D-Ala2,N-Me-Phe4,Gly5]-ol-enkephalin
      (DAMGO) significantly elevated the mechanical thresholds of nociceptive Adelta
      and C fibres. Furthermore, DAMGO substantially diminished the mechanically evoked
      discharges of C nociceptors in injured nerves. These effects were blocked by
      DAMGO washout and pre-treatment with the selective MU-opioid receptor antagonist
      Cys2-Tyr3-Orn5-Pen7-amide. DAMGO did not alter the responses of sensory fibres in
      uninjured nerves. CONCLUSIONS: Our findings suggest that behaviourally manifested
      neuropathy-induced mechanosensitivity does not require a sensitised state of
      cutaneous nociceptors in damaged nerves. Yet, nerve injury renders nociceptors
      sensitive to opioids. Prevention of action potential generation or propagation in
      nociceptors might represent a cellular mechanism underlying peripheral opioid
      mediated alleviation of mechanical hypersensitivity in neuropathy.

PMID- 23116257
TI  - Performance evaluation of algorithms for the classification of metabolic 1H NMR
      fingerprints.
AB  - Nontargeted metabolite fingerprinting is increasingly applied to biomedical
      classification. The choice of classification algorithm may have a considerable
      impact on outcome. In this study, employing nested cross-validation for assessing
      predictive performance, six binary classification algorithms in combination with
      different strategies for data-driven feature selection were systematically
      compared on five data sets of urine, serum, plasma, and milk one-dimensional
      fingerprints obtained by proton nuclear magnetic resonance (NMR) spectroscopy.
      Support Vector Machines and Random Forests combined with t-score-based feature
      filtering performed well on most data sets, whereas the performance of the other
      tested methods varied between data sets.

PMID- 23116258
TI  - Two pyrenylalanines in dihydrofolate reductase form an excimer enabling the study
      of protein dynamics.
AB  - Because of the lack of sensitivity to small changes in distance by available FRET
      pairs (a constraint imposed by the dimensions of the enzyme), a DHFR containing
      two pyrene moieties was prepared to enable the observation of excimer formation.
      Pyren-1-ylalanine was introduced into DHFR positions 16 and 49 using an in vitro
      expression system in the presence of pyren-1-ylalanyl-tRNA(CUA). Excimer
      formation (lambda(ex) 342 nm; lambda(em) 481 nm) was observed in the modified
      DHFR, which retained its catalytic competence and was studied under multiple and
      single turnover conditions. The excimer appeared to follow a protein
      conformational change after the H transfer involving the relative position and
      orientation of the pyrene moieties and is likely associated with product
      dissociation.

PMID- 23116259
TI  - Cellular uptake and toxic effects of fine and ultrafine metal-sulfate particles
      in human A549 lung epithelial cells.
AB  - Ambient airborne particulate matter is known to cause various adverse health
      effects in humans. In a recent study on the environmental impacts of coal and
      tire combustion in a thermal power station, fine crystals of PbSO(4) (anglesite),
      ZnSO(4).H(2)O (gunningite), and CaSO(4) (anhydrite) were identified in the stack
      emissions. Here, we have studied the toxic potential of these sulfate phases as
      particulates and their uptake in human alveolar epithelial cells (A549). Both
      PbSO(4) and CaSO(4) yielded no loss of cell viability, as determined by the WST-1
      and NR assays. In contrast, a concentration-dependent increase in cytotoxicity
      was observed for Zn sulfate. For all analyzed sulfates, an increase in the
      production of reactive oxygen species (ROS), assessed by the DCFH-DA assay and
      EPR, was observed, although to a varying extent. Again, Zn sulfate was the most
      active compound. Genotoxicity assays revealed concentration-dependent DNA damage
      and induction of micronuclei for Zn sulfate and, to a lower extent, for CaSO(4),
      whereas only slight effects could be found for PbSO(4). Moreover, changes of the
      cell cycle were observed for Zn sulfate and PbSO(4). It could be shown further
      that Zn sulfate increased the nuclear factor kappa-B (NF-kappaB) DNA binding
      activity and activated JNK. During our TEM investigations, no effect on the
      appearance of the A549 cells exposed to CaSO(4) compared to the nonexposed cells
      was observed, and in our experiments, only one CaSO(4) particle was detected in
      the cytoplasm. In the case of exposure to Zn sulfate, no particles were found in
      the cytoplasm of A549 cells, but we observed a concentration-dependent increase
      in the number and size of dark vesicles (presumably zincosomes). After exposure
      to PbSO(4), the A549 cells contained isolated particles as well as agglomerates
      both in vesicles and in the cytoplasm. Since these metal-sulfate particles are
      emitted into the atmosphere via the flue gas of coal-fired power stations, they
      may be globally abundant. Therefore, our study is of direct relevance to
      populations living near such power plants.

PMID- 23116260
TI  - Ag@BSA core/shell microspheres as an electrochemical interface for sensitive
      detection of urinary retinal-binding protein.
AB  - The level of urinary retinol-binding protein (RBP) can be estimated as a
      significant index of renal tubular injury. In this work, we used Ag@BSA
      microspheres as a sensing interface to cross-link RBP monoclonal antibody (RBP
      mAb) via glutaraldehyde for sensitive detection of RBP. The Ag@BSA microspheres
      covered on a Au electrode could provide a larger surface area and multifunctional
      substrate for the effective immobilization of RBP mAb, and the outside BSA layer
      acted as a biocompatible support to maintain the bioactivity and stability of
      immobilized immunogen. Electrochemical measurements containing electrochemical
      impedance spectroscopy (EIS) and differential pulse voltammetry (DPV) were
      employed to evaluate the analytical performance of the fabricated immunosensor
      and a higher detection sensitivity was obtained by DPV attributed to the
      excellent electrical conductivity of Ag@BSA which could enhance the peak current
      response. This immunosensor had a best detection limit (DL) of 18 ng mL(-1) and a
      linear response range between 50 and 4500 ng mL(-1). The proposed approach showed
      high specificity for RBP detection, acceptable reproducibility with an RSD of
      5.6%, and good precision with the RSD of 4.5% and 6.3% at the RBP concentrations
      of 500 and 1500 ng mL(-1). Compared with the ELISA method by analyzing real urine
      samples from a patient, this immunosensor revealed acceptable accuracy with a
      relative deviation lower than 6.5%, indicating a potential alternative method for
      RBP detection in clinical diagnosis.

PMID- 23116261
TI  - Simultaneous analysis of 17 diuretics in dietary supplements by HPLC and LC
      MS/MS.
AB  - In order to test health foods for illegally added diuretics for weight loss, we
      developed simple, rapid, selective, and sensitive methods using HPLC and LC-MS/MS
      for the simultaneous analysis of 17 diuretics in dietary supplements. HPLC
      conditions were set with a Capcell-pak C18, using a mobile phase consisting of
      gradient conditions, UV detection at 254 nm and validated for linearity (r(2)>
      0.999), precision (CV <= 3%), recoveries (90.4-102.8%) and reproducibility.
      Identification and quantification of 17 diuretics were accomplished by ion-spray
      LC-MS/MS using multiple reaction monitoring (MRM). The chromatographic separation
      was carried out under the reversed-phase mechanism on an HSS-T3 column. The LC
      MS/MS method was validated for linearity (r(2)> 0.99) and precision (CV < 13%).
      Sixteen dietary supplements were tested with the developed methods. Diuretics
      were not detected in all samples. Extraction recovery was also investigated and
      the extraction recoveries in different formulations were from 88% to 110% and
      from 81% to 116% using HPLC and LC-MS/MS, respectively. There was no significant
      difference in recoveries in the type of dietary supplements. Based on this
      result, the developed methods to monitor illegal drug adulterations in dietary
      supplements using HPLC and LC-MS/MS are simple, fast and reliable. Therefore, it
      is applicable to routine drug-adulteration screening.

PMID- 23116262
TI  - In vitro effect of gold and silver nanoparticles on human spermatozoa.
AB  - The cytotoxicity of Au/Ag nanoparticles (NPs) on human spermatozoa was
      investigated in vitro. Semen from donors were incubated (37  degrees C, 60'-120')
      with 30, 60, 125, 250 and 500 MUM Au/Ag-NPs. Sperm motility was evaluated
      following WHO guidelines; sperm viability was assessed with eosin Y test. Au-NPs
      were characterised and localised with field emission gun-based scanning
      transmission electron microscope/energy dispersive spectroscopy and transmission
      electron microscopy. Both tested NPs exerted a significant dose-dependent effect
      on motility and viability of human spermatozoa (P < 0.001). Ag-NPs seem to show a
      slightly elevated toxicity although not significant (P > 0.05). Au-NPs were
      localised in spermatozoa, whereas Ag-NPs were undetectable. In conclusion, Au-NPs
      and Ag-NPs do not appear to be harmful for human spermatozoa up to high
      concentrations (250-500 MUM) that are probably difficult to reach in vivo. It is
      mandatory to explore the genotoxic effect of NPs in germ cells. 

PMID- 23116263
TI  - The aryl hydrocarbon receptor nuclear translocator (ARNT) family of proteins:
      transcriptional modifiers with multi-functional protein interfaces.
AB  - The basic Helix-Loop-Helix/PER-ARNT-SIM (bHLH-PAS) domain family of transcription
      factors mediates cellular responses to a variety of internal and external
      stimuli. As functional transcription factors, these proteins act as bHLH-PAS
      heterodimers and can be further sub-classified into sensory/activated subunits
      and regulatory or ARNT-like proteins. This class of proteins act as master
      regulators of the bHLH-PAS superfamily of transcription factors that mediate
      circadian rhythm gene programs, innate and adaptive immune responses, oxygen
      sensing mechanisms and compensate for deleterious environmental exposures. Some
      contribute to the etiology of human pathologies including cancer because of their
      effects on cell growth and metabolism. We will review the canonical roles of ARNT
      and ARNT-like proteins with an emphasis on coactivator selectivity and
      recruitment. We will also discuss recent advances in our understanding of
      noncanonical DNA-binding independent or off-target roles of ARNT that are
      uncoupled from its classic heterodimeric bHLH-PAS binding partners. Understanding
      the DNA binding-independent functions of ARNT may identify novel therapeutic
      options for the treatment of a large spectrum of disease states. 

PMID- 23116264
TI  - Nuclear hormone receptors and female reproduction.
AB  - BACKGROUND: Nuclear Hormone Receptors (NHR) are, as the name implies, receptors
      located in the cell nucleus that have transcription modulating characteristics.
      Activated non-steroidal lipophilic ligands bind these receptors resulting in
      dimerisation of the ligands, DNA-binding and transcriptional regulation of target
      proteins that influence especially cell differentiation, metabolic homeostasis
      and embryogenesis. METHODS: This review is based on publications derived from
      PubMed based pursuit of scientific literature in conjunction with the authors'
      experience. RESULTS: Here, a summary of NHR family members (RXR, PPAR, VDR, TR)
      first in respect to known general aspects such as ligands, binding domains,
      signalling mechanism and second focussing especially their influence on female
      reproduction is offered. Furthermore, crosstalk with other prominent signalling
      proteins important to trophoblast function [signal transducer and activator of
      transcription (STAT), mitogen-activated protein kinase (MAPK), nuclear factor
      'kappa-light-chain-enhancer' of activated B-cells (NFkappaB), Akt/ phosphaidyl-3
      kinase (PI3K), and Wnt, are described. CONCLUSION: Considering their attributes,
      it is not surprising that NHR family members play a central role in female
      reproduction by targeting cell differentiation, metabolic homeostasis and
      embryogenesis. However, it seems that crosstalk depends on stage of trophoblast
      differentiation.

PMID- 23116265
TI  - C-Jun terminal kinases play an important role in regulating embryonic survival
      and eye development in vertebrates.
AB  - The c-Jun N-terminal kinases (JNKs) constitute one of the three major types of
      mitogen-activated protein kinases. Previous studies showed that JNK mediates
      multiple signaling transduction pathways implicated in cell proliferation,
      differentiation, inflammation, stress response and apoptosis in mammals. In the
      present study, we use goldfish as a model system and demonstrate that JNK kinases
      are necessary to promote embryonic survival and regulate eye development in
      vertebrates. During goldfish development, JNK1 and JNK2 are expressed at every
      stage from cleavage to hatching larvae. JNK3 is turned on at the gastrulation
      stage and then expressed at similar level to that of JNK2. JNK1 activity remains
      slightly fluctuated during different developmental stages. Inhibition of JNK
      activity caused massive apoptosis of blastula cells and significant death of
      goldfish embryos, which are associated with altered expression of the anti
      apoptotic regulator, Mcl-1 and the proapoptotic regulator, Bak. These results
      provide novel information regarding the mechanisms by which JNKs promote
      embryonic survival. In addition, the embryos that survived inhibition of JNK
      activity displayed severe phenotype in the eye with clear microphthalmia and lens
      coloboma. To confirm that the observed phenotype is derived from JNK activity
      deficiency, we expressed JNK dominant negative mutant (DNM-JNK) in goldfish.
      Expression of DNM-JNK also caused similar phenotypes with altered expression of
      pax-6, Sox-2 and beta-crystallin. Together, our results demonstrate that JNKs
      play important roles in promoting survival of vertebrate embryos and regulating
      development of vertebrate eye.

PMID- 23116266
TI  - EGFR and the complexity of receptor crosstalk in the cardiovascular system.
AB  - Signaling pathways play a critical role in the maintenance of cellular structure
      and function. These pathways can act together with synergistic or antagonistic
      outcome. Cooperative and integrative cellular communication networks, otherwise
      known as crosstalk can amplify signaling cascades. Here, we focus on receptor
      crosstalk in the context of cardiovascular pathologies, mainly involving the
      epidermal growth factor receptor (EGFR), a critical mediator of multiple receptor
      pathways in normal physiological and pathophysiological processes. Considerable
      experimental evidence suggests that the uncontrolled expression of EGFR
      contributes to tumorigenesis through inhibition of apoptosis, angiogenesis,
      anchorage-independent growth and tumor-associated inflammation. Abnormal
      activation of the intrinsic tyrosine kinase of EGFR through mutation or
      overexpression is observed in various human cancer types. On the other hand, the
      role of EGFR in vascular biology is not well understood. In cardiovascular
      pathologies, such as atherosclerosis and restenosis, vascular smooth muscle cells
      (SMCs) migrate and proliferate, contributing to neointima formation, whilst
      apoptosis may cause plaque instability. EGFR can be transactivated by numerous
      pathologic stimuli that regulate SMC behaviour. This review describes our current
      understanding of the role of EGFR in SMC biology and pathology.

PMID- 23116269
TI  - Please, let us in.

PMID- 23116267
TI  - The weal and woe of costimulation in the adoptive therapy of cancer with chimeric
      antigen receptor (CAR)-redirected T cells.
AB  - Adoptive cell therapy has shown impressive efficacy to combat cancer in early
      phase clinical trials, in particular when T cells engineered to specifically
      target tumor cells were applied. The patient's T cells are genetically equipped
      with a chimeric antigen receptor (CAR) which allows them to be redirected in a
      predefined manner towards virtually any target; by using an antibody-derived
      domain for binding, CAR T cells can be redirected in a major histocompatibility
      complex (MHC) dependent and independent fashion. The CAR also provides the
      stimuli required to induce and maintain T cell activation. Recent clinical data
      sustain the notion that strong costimulation in conjunction with the primary
      activation signal is crucial for lasting therapeutic efficacy of CAR T cells.
      However, costimulation is a double-edged sword and the impact of the individual
      costimuli to optimize T cell activation is still under debate; some general rules
      are emerging. The review summarizes how costimulation modulates, improves and
      prolongs the redirected anti-tumor T cell response and how the same costimulatory
      signals may contribute to unintended side effects including "cytokine storm" and
      T cell repression. Upcoming strategies to break the activation/repression circle
      by using CAR's with modified costimulatory signals are also discussed. 

PMID- 23116270
TI  - Palliation in adolescent and young adult HIV medicine--an emerging need.

PMID- 23116271
TI  - Tips for palliative care professionals treating mesothelioma patients.

PMID- 23116272
TI  - Laughing at the dark: tactical humor for autonomous decision making in serious
      illness.

PMID- 23116273
TI  - Withdrawal of dialysis: decision making #207.

PMID- 23116274
TI  - Clinical care following withdrawal of dialysis #208.

PMID- 23116275
TI  - One last dose.

PMID- 23116276
TI  - My son's second birthday.

PMID- 23116277
TI  - Dispatches from palliative care rounds.

PMID- 23116278
TI  - Just my luck.

PMID- 23116281
TI  - Self-assembling modified beta-cyclodextrin nanoparticles as neuronal siRNA
      delivery vectors: focus on Huntington's disease.
AB  - Huntington's disease (HD) is a rare autosomal dominant neurodegenerative disease
      caused by the expression of a toxic Huntingtin (HTT) protein. The use of short
      interfering RNAs (siRNAs) to silence the mutant protein is one of the most
      promising therapeutic strategies under investigation. The biggest caveat to siRNA
      based approaches is the lack of efficient and nontoxic delivery vectors for siRNA
      delivery to the central nervous system. In this study, we investigated the
      potential of modified amphiphilic beta-cyclodextrins (CDs), oligosaccharide-based
      molecules, as novel siRNA neuronal carriers. We show that CDs formed nanosize
      particles which were stable in artificial cerebrospinal fluid. Moreover, these
      complexes were able to reduce the expression of the HTT gene in rat striatal
      cells (ST14A-HTT120Q) and in human HD primary fibroblasts. Only limited toxicity
      was observed with CD.siRNA nanoparticles in any of the in vitro models used.
      Sustained knockdown effects were observed in the striatum of the R6/2 mouse model
      of HD after single direct injections of CD.siRNA nanoparticles. Repeated brain
      injections of CD.siRNA complexes resulted in selective alleviation of motor
      deficits in this mouse model. Together these data support the utility of modified
      beta-CDs as efficient and safe siRNA delivery vectors for RNAi-based therapies
      for neuropsychiatric and neurodegenerative disorders.

PMID- 23116282
TI  - smRNAome profiling to identify conserved and novel microRNAs in Stevia rebaudiana
      Bertoni.
AB  - BACKGROUND: MicroRNAs (miRNAs) constitute a family of small RNA (sRNA) population
      that regulates the gene expression and plays an important role in plant
      development, metabolism, signal transduction and stress response. Extensive
      studies on miRNAs have been performed in different plants such as Arabidopsis
      thaliana, Oryza sativa etc. and volume of the miRNA database, mirBASE, has been
      increasing on day to day basis. Stevia rebaudiana Bertoni is an important
      perennial herb which accumulates high concentrations of diterpene steviol
      glycosides which contributes to its high indexed sweetening property with no
      calorific value. Several studies have been carried out for understanding
      molecular mechanism involved in biosynthesis of these glycosides, however,
      information about miRNAs has been lacking in S. rebaudiana. Deep sequencing of
      small RNAs combined with transcriptomic data is a powerful tool for identifying
      conserved and novel miRNAs irrespective of availability of genome sequence data.
      RESULTS: To identify miRNAs in S. rebaudiana, sRNA library was constructed and
      sequenced using Illumina genome analyzer II. A total of 30,472,534 reads
      representing 2,509,190 distinct sequences were obtained from sRNA library. Based
      on sequence similarity, we identified 100 miRNAs belonging to 34 highly conserved
      families. Also, we identified 12 novel miRNAs whose precursors were potentially
      generated from stevia EST and nucleotide sequences. All novel sequences have not
      been earlier described in other plant species. Putative target genes were
      predicted for most conserved and novel miRNAs. The predicted targets are mainly
      mRNA encoding enzymes regulating essential plant metabolic and signaling
      pathways. CONCLUSIONS: This study led to the identification of 34 highly
      conserved miRNA families and 12 novel potential miRNAs indicating that specific
      miRNAs exist in stevia species. Our results provided information on stevia miRNAs
      and their targets building a foundation for future studies to understand their
      roles in key stevia traits.

PMID- 23116283
TI  - Preparation of Coenzyme Q10 nanostructured lipid carriers for epidermal targeting
      with high-pressure microfluidics technique.
AB  - OBJECTIVE: The objective of this work was to prepare coenzyme Q10 loaded
      nanostructured lipid carriers (Q10-NLC) and evaluate its epidermal targeting
      effect. METHODS: Q10-NLC was prepared by high-pressure microfluidics technique.
      Formulations and preparation parameters were optimized with response surface
      design. Q10-NLC was characterized by PCS, TEM, DSC and PXRD. The penetration of
      Q10 from the Q10-NLC formulations through skins and into skins were evaluated in
      vitro using Franz diffusion cells fitted with SD rat skins. In vitro release,
      long-term stability and light stability were also evaluated. RESULTS: The results
      showed that the concentration of solid lipid and emulsifier in formulation had a
      significant influence on particle size. The optimized preparation parameters were
      magnetic stirring for 20 min, high stirring at 8000 rpm for 1 min and high
      pressure microfluidics at 1200 bar for three cycles. The size of Q10-NLC prepared
      by optimized formulation and parameters was (151.7 +/- 2.31) nm, polydispersity
      (PDI) 0.144, zeta potential was (-44.1 +/- 1.68) mV, drug loading 2.51%,
      encapsulation efficiency 100%. In vitro release study, Q10-NLC showed fast
      release during the first 3 hours and prolonged release afterwards. In vitro skin
      permeation study, the accumulative uptake of Q10 in epidermal of Q10-NLC was
      10.11 times over Q10 emulsion. After exposure to day light for 24 hours, the
      amount of Q10 in Q10-NLC decreased only 5.59%, while in Q10 emulsion decreased
      24.61% and Q10-ethanol solution 49.74%. CONCLUSION: Q10-NLC exhibited a
      significant epidermal targeting effect, which was proved to be a promising
      carrier for topical delivery of Q10.

PMID- 23116284
TI  - Estrogen receptor alpha gene (ESR1) polymorphisms associated with idiopathic
      premature ovarian failure in Chinese women.
AB  - OBJECTIVE: To evaluate the relationship between Estrogen receptor alpha gene
      (ESR1) polymorphisms and idiopathic premature ovarian failure (POF) in Chinese
      women. METHODS: 155 idiopathic POF and 150 healthy controls were recruited in
      this study. All subjects were analyzed at the PvuII and XbaI loci of the ESR1
      gene using polymerase chain reaction (PCR)-restriction fragment length
      polymorphism (RFLP). RESULTS: The frequency of the P allele of the PvuII
      polymorphisms was 38.1% in POF women, which was significantly higher than
      controls (28.0%) (p = 0.008). And for the XbaI polymorphisms, the X allele was
      21.0% in POF patients, compared to 13.3% in control women (p = 0.013). Carriers
      of the PP genotype had higher increased risk of POF than those of the pp
      genotypes (p = 0.011), whereas in three genotypes of the XbaI polymorphisms, no
      difference was found in the prediction value of POF. In addiction, the P-X
      haplotype was associated with a significantly increased risk for idiopathic POF.
      CONCLUSION: These data suggest that the PvuII and XbaI polymorphisms of ESR1 gene
      are associated with POF, which may be a potential genetic risk factor of
      idiopathic POF. More researches are needed to determine whether the findings are
      generalizable to other populations.

PMID- 23116285
TI  - Controlled release of doxorubicin loaded within magnetic thermo-responsive
      nanocarriers under magnetic and thermal actuation in a microfluidic channel.
AB  - We report a procedure to grow thermo-responsive polymer shells at the surface of
      magnetic nanocarriers made of multiple iron oxide superparamagnetic nanoparticles
      embedded in poly(maleic anhydride-alt-1-ocatadecene) polymer nanobeads. Depending
      on the comonomers and on their relative composition, tunable phase transition
      temperatures in the range between 26 and 47  degrees C under physiological
      conditions could be achieved. Using a suitable microfluidic platform combining
      magnetic nanostructures and channels mimicking capillaries of the circulatory
      system, we demonstrate that thermo-responsive nanobeads are suitable for
      localized drug delivery with combined thermal and magnetic activation. Below the
      critical temperature nanobeads are stable in suspension, retain their cargo, and
      cannot be easily trapped by magnetic fields. Increasing the temperature above the
      critical temperature causes the aggregation of nanobeads, forming clusters with a
      magnetic moment high enough to permit their capture by suitable magnetic
      gradients in close proximity to the targeted zone. At the same time the polymer
      swelling activates drug release, with characteristic times on the order of one
      hour for flow rates of the same order as those of blood in capillaries.

PMID- 23116286
TI  - Autumn advances towards 2013.

PMID- 23116287
TI  - Functional modular dissection of DEBS1-TE changes triketide lactone ratios and
      provides insight into Acyl group loading, hydrolysis, and ACP transfer.
AB  - The DEBS1-TE fusion protein is comprised of the loading module, the first two
      extension modules, and the terminal TE domain of the Saccharopolyspora erythraea
      6-deoxyerythronolide B synthase. DEBS1-TE produces triketide lactones that differ
      on the basis of the starter unit selected by the loading module. Typical
      fermentations with plasmid-based expression of DEBS1-TE produce a 6:1 ratio of
      propionate to isobutyrate-derived triketide lactones. Functional dissection of
      the loading module from the remainder of DEBS1-TE results in 50% lower titers of
      triketide lactone and a dramatic shift in the production to a 1:4 ratio of
      propionate to isobutyrate-derived products. A series of radiolabeling studies of
      the loading module has shown that transfer from the AT to the ACP occurs much
      faster for propionate than for isobutyrate. However, the equilibrium occupancy of
      the AT favors isobutyrate such that propionate is outcompeted for ACP occupancy.
      Thus, propionyl-ACP is the kinetic product, while isobutyryl-ACP is the
      thermodynamic product. A slowed transfer from the loading domain ACP to first
      extension module KS due to functional dissection of DEBS1-TE allows this
      isobutyryl-ACP-favored equilibrium to be realized and likely accounts for the
      observed shift in triketide lactone products.

PMID- 23116288
TI  - Potential of oncostatin M to accelerate diabetic wound healing.
AB  - Oncostatin M (OSM) is a multifunctional cytokine found in a variety of pathologic
      conditions, which leads to excessive collagen deposition. Current studies
      demonstrate that OSM is also a mitogen for fibroblasts and has an anti
      inflammatory action. It was therefore hypothesised that OSM may play an important
      role in healing of chronic wounds that usually involve decreased fibroblast
      function and persist in the inflammatory stage for a long time. In a previous in
      vitro study, the authors showed that OSM increased wound healing activities of
      diabetic dermal fibroblasts. However, wound healing in vivo is a complex process
      involving multiple factors. Thus, the purpose of this study was to evaluate the
      effect of OSM on diabetic wound healing in vivo. Five diabetic mice were used in
      this study. Four full-thickness round wounds were created on the back of each
      mouse (total 20 wounds). OSM was applied on the two left-side wounds (n = 10) and
      phosphate-buffered saline was applied on the two right-side wounds (n = 10).
      After 10 days, unhealed wound areas of the OSM and control groups were compared
      using the stereoimage optical topometer system. Also, epithelialisation, wound
      contraction and reduction in wound volume in each group were compared. The OSM
      treated group showed superior results in all of the tested parameters. In
      particular, the unhealed wound area and the reduction in wound volume
      demonstrated statistically significant differences (P < 0.05). The results of
      this study indicate that topical application of OSM may have the potential to
      accelerate healing of diabetic wounds.

PMID- 23116289
TI  - Continuous time simulation and discretized models for cost-effectiveness
      analysis.
AB  - The design of decision-analytic models for cost-effectiveness analysis has been
      the subject of discussion. The current work addresses this issue by noting that,
      when time is to be explicitly modelled, we need to represent phenomena occurring
      in continuous time. Models evaluated in continuous time may not have closed-form
      solutions, and in this case, two approximations can be used: simulation models in
      continuous time and discretized models at the aggregate level. Stylized examples
      were set up where both approximations could be implemented. These aimed to
      illustrate determinants of the use of the two approximations: cycle length and
      precision, the use of continuity corrections in discretized models and the
      discretization of rates into probabilities. The examples were also used to
      explore the impact of the approximations not only in terms of absolute survival
      but also cost effectiveness and incremental comparisons. Discretized models
      better approximate continuous time results if lower cycle lengths are used.
      Continuous time simulation models are inherently stochastic, and the precision of
      the results is determined by the simulation sample size. The use of continuity
      corrections in discretized models allows the use of greater cycle lengths,
      producing no significant bias from the discretization. How the process is
      discretized (the conversion of rates into probabilities) is key. Results show
      that appropriate discretization coupled with the use of a continuity correction
      produces results unbiased for higher cycle lengths. Alternative methods of
      discretization are less efficient, i.e. lower cycle lengths are needed to obtain
      unbiased results. The developed work showed the importance of acknowledging bias
      in estimating cost effectiveness. When the alternative approximations can be
      applied, we argue that it is preferable to implement a cohort discretized model
      rather than a simulation model in continuous time. In practice, however, it may
      not be possible to represent the decision problem by any conventionally defined
      discretized model, in which case other model designs need to be applied, e.g. a
      simulation model.

PMID- 23116290
TI  - Impact of transformation of negative values and regression models on differences
      between the UK and US EQ-5D time trade-off value sets.
AB  - BACKGROUND: National EQ-5D value sets are developed because preferences for
      health may vary in different populations. UK values are lower than US values for
      most of the 243 possible EQ-5D health states. Although similar protocols were
      used for data collection, analytic choices regarding how to model values from the
      collected data may also influence national value sets. Participants in the UK and
      US studies assessed the same subset of 42 EQ-5D health states using the time
      trade-off (TTO) method. However, different methods were used to transform
      negative values to a range bounded by 0 and -1, and values for all 243 health
      states were estimated using two different regression models. The transformation
      of negative values is inconsistent with expected utility theory, and the choice
      of which transformation method to use lacks a theoretical foundation. OBJECTIVES:
      Our objectives were to assess how much of the observed difference between the UK
      and US EQ-5D value sets may be explained by the choice of transformation method
      for negative values relative to the choice of regression model and the
      differences between elicited TTO values in the respective national studies
      (datasets). METHODS: We applied both transformation methods and both regression
      models to each of the two datasets, resulting in eight comparable value sets. We
      arranged these value sets in pairs in which one source of difference
      (transformation method, regression model or dataset) was varied. For each of
      these paired value sets, we calculated the mean difference between the two
      matching values for each of the 243 health states. Finally, we calculated the
      mean utility gain for all possible transitions between pairs of EQ-5D health
      states within each value set and used the difference in transition scores as a
      measure of impact from changing transformation method, regression model or
      dataset. RESULTS: The mean absolute difference in values was 1.5 times larger
      when changing the transformation method than when using different datasets. The
      choice of transformation method had a 3.2 times larger effect on the mean health
      gain (transition score) than the choice of dataset. The mean health gain in the
      UK value set was 0.09 higher than in the US value set. Using the UK
      transformation method on the US dataset reduced this absolute difference to 0.02.
      The choice of regression model had little overall impact on the differences
      between the value sets. CONCLUSIONS: Most of the observed differences between the
      UK and US value sets were caused by the use of different transformation methods
      for negative values, rather than differences between the two study populations as
      reflected in the datasets. Changing the regression model had little impact on the
      differences between the value sets.

PMID- 23116291
TI  - Different thresholds of tissue-specific dose-responses to growth hormone in short
      prepubertal children.
AB  - BACKGROUND: In addition to stimulating linear growth in children, growth hormone
      (GH) influences metabolism and body composition. These effects should be
      considered when individualizing GH treatment as dose-dependent changes in
      metabolic markers have been reported. HYPOTHESIS: There are different dose
      dependent thresholds for metabolic effects in response to GH treatment. METHOD: A
      randomized, prospective, multicentre trial TRN 98-0198-003 was performed for a 2
      year catch-up growth period, with two treatment regimens (a) individualized GH
      dose including six different dose groups ranging from 17-100 MUg/kg/day (n=87)
      and (b) fixed GH dose of 43 MUg/kg/day (n=41). The individualized GH dose group
      was used for finding dose-response effects, where the effective GH dose (ED 50%)
      required to achieve 50% Delta effect was calculated with piecewise linear
      regressions. RESULTS: Different thresholds for the GH dose were found for the
      metabolic effects. The GH dose to achieve half of a given effect (ED 50%, with
      90% confidence interval) was calculated as 33(+/-24.4) MUg/kg/day for Delta left
      ventricular diastolic diameter (cm), 39(+/-24.5) MUg/kg/day for Delta alkaline
      phosphatase (MUkat/L), 47(+/-43.5) MUg/kg/day for Delta lean soft tissue (SDS),
      48(+/-35.7) MUg/kg/day for Delta insulin (mU/L), 51(+/-47.6) MUg/kg/day for Delta
      height (SDS), and 57(+/-52.7) MUg/kg/day for Delta insulin-like growth factor I
      (IGF-I) SDS. Even though lipolysis was seen in all subjects, there was no  dose
      response effect for Delta fat mass (SDS) or Delta leptin ng/ml in the dose range
      studied. None of the metabolic effects presented here were related to the dose
      selection procedure in the trial. CONCLUSIONS: Dose-dependent thresholds were
      observed for different GH effects, with cardiac tissue being the most responsive
      and level of IGF-I the least responsive. The level of insulin was more responsive
      than that of IGF-I, with the threshold effect for height in the interval between.

PMID- 23116292
TI  - An endohedral metallofullerene as a pure electron donor: intramolecular electron
      transfer in donor-acceptor conjugates of La2@C80 and 11,11,12,12-tetracyano-9,10
      anthra-p-quinodimethane (TCAQ).
AB  - An endohedral metallofullerene, La(2)@C(80), is covalently linked to the strong
      electron acceptor 11,11,12,12-tetracyano-9,10-anthra-p-quinodimethane (TCAQ) by
      means of the Prato reaction, affording two different [5,6]
      metallofulleropyrrolidines, namely 1a and 2a. 1a and 2a were isolated and fully
      characterized by means of MALDI-TOF mass, UV-vis-NIR absorption, and NMR
      spectroscopies. In addition, cyclic voltammetry (CV) and differential pulse
      voltammetry (DPV) corroborated the unique redox character of 2a, that is, the
      presence of the electron-donating La(2)@C(80) and the electron-accepting TCAQ.
      Although a weak electronic coupling dictates the interactions between La(2)@C(80)
      and TCAQ in the ground state, time-resolved transient absorption experiments
      reveal that in the excited state (i.e., pi-pi* centered at La(2)@C(80)) the
      unprecedented formation of the (La(2)@C(80))(*+)-(TCAQ)(*-) radical ion pair
      state evolves in nonpolar and polar media with a quantum efficiency of 33%.

PMID- 23116293
TI  - Nucleus-independent chemical shifts and aromaticity in hexanuclear cluster
      complexes [Mo6X8]n- (X = S, Se, and Te; n = 0 and 4) of Chevrel phases.
AB  - Molecular diamagnetism and multicentered X-Mo-Mo and Mo-Mo-Mo interactions in
      hexanuclear cluster complexes [Mo(6)X(8)](n-) (X = S, Se, and Te; n = 0 and 4)
      are studied using calculations of nuclear independent chemical shifts (NICS) and
      the methods "atoms in molecules" and electron localization function. It is shown
      that [Mo(6)X(8)](4-) complexes are characterized by large negative NICSs related
      to the aromaticity of Mo-Mo bondings and to diatropic currents in Mo(6) metallic
      core of the cuboctahedral clusters. The calculated  currents can participate in
      the mechanism of  nucleation of the vortex lattice of macroscopic Abrikosov's
      electronic whirls responsible for the magnetic high-field stability of the
      superconducting currents in type II superconductors.

PMID- 23116294
TI  - Developing a Danish version of the "Impact on Participation and Autonomy
      Questionnaire".
AB  - OBJECTIVE: To translate the "Impact on Participation and Autonomy Questionnaire"
      into Danish (IPAQ-DK), and estimate its internal consistency and test-retest
      reliability in order to promote participation-based interventions and research.
      DESIGN: Translation and two successive reliability assessments through test
      retest. SUBJECTS: 137 adults with varying degrees of impairment; of these, 67
      participated in the final reliability assessment. METHODS: The translation
      followed guidelines set forth by the "European Group for Quality of Life
      Assessment and Health Measurement". Internal consistency for subscales was
      estimated by Chronbach's alpha. Weighted kappa coefficients and intraclass
      correlation coefficients were calculated to assess the test-retest reliability at
      item and subscale level, respectively. RESULTS: A preliminary reliability
      assessment revealed residual issues regarding the translation and cultural
      adaptation of the instrument. The revised version (IPAQ-DK) was subsequently
      subjected to a similar assessment demonstrating Chronbach's alpha values from
      0.698 to 0.817. Weighted kappa ranged from 0.370 to 0.880; 78% of these values
      were higher than 0.600. The intraclass correlation coefficient covered values
      from 0.701 to 0.818. CONCLUSION: IPAQ-DK is a useful instrument for identifying
      person-perceived participation restrictions and satisfaction with participation.
      Further studies of IPAQ-DK's floor/ceiling effects and responsiveness to change
      are recommended, and whether there is a need for further linguistic improvement
      of certain items.

PMID- 23116295
TI  - Design strategies for development of SCR catalyst: improvement of alkali
      poisoning resistance and novel regeneration method.
AB  - Based on the ideas of the additives modification and regeneration method update,
      two different strategies were designed to deal with the traditional SCR catalyst
      poisoned by alkali metals. First, ceria doping on the V(2)O(5)-WO(3)/TiO(2)
      catalyst could promote the SCR performance even reducing the V loading, which
      resulted in the enhancement of the catalyst's alkali poisoning resistance. Then,
      a novel method, electrophoresis treatment, was employed to regenerate the alkali
      poisoned V(2)O(5)-WO(3)/TiO(2) catalyst. This novel technique could dramatically
      enhance the SCR activities of the alkali poisoned catalysts by removing
      approximately 95% K or Na ions from the catalyst and showed less hazardous to the
      environment. Finally, the deactivation mechanisms by the alkali metals were
      extensively studied by employing both the experimental and DFT theoretical
      approaches. Alkali atom mainly influences the active site V species rather than W
      oxides. The decrease of catalyst surface acidity might directly reduce the
      catalytic activity, while the reducibility of catalysts could be another
      important factor.

PMID- 23116296
TI  - Discovery of SLC3A2 cell membrane protein as a potential gastric cancer
      biomarker: implications in molecular imaging.
AB  - Despite decreasing incidence and mortality, gastric cancer remains the second
      leading cause of cancer-related deaths in the world. Successful management of
      gastric cancer is hampered by lack of highly sensitive and specific biomarkers
      especially for early cancer detection. Cell surface proteins that are aberrantly
      expressed between normal and cancer cells are potentially useful for cancer
      imaging and therapy due to easy accessibility of these targets. Combining two
      phase partition and isobaric tags for relative and absolute quantification
      methods, we compared the relative expression levels of membrane proteins between
      noncancer and gastric cancer cells. About 33% of the data set was found to be
      plasma membrane and associated proteins using this approach (compared to only 11%
      in whole cell analysis), several of which have never been previously implicated
      in gastric cancer. Upregulation of SLC3A2 in gastric cancer cells was validated
      by immunoblotting of a panel of 13 gastric cancer cell lines and
      immunohistochemistry on tissue microarrays comprising 85 matched pairs of normal
      and tumor tissues. Immunofluorescence and immunohistochemistry both confirmed the
      plasma membrane localization of SLC3A2 in gastric cancer cells. The data
      supported the notion that SLC3A2 is a potential biomarker that could be exploited
      for molecular imaging-based detection of gastric cancer.

PMID- 23116297
TI  - Direct measurement of oleocanthal and oleacein levels in olive oil by
      quantitative (1)H NMR. Establishment of a new index for the characterization of
      extra virgin olive oils.
AB  - A new method for direct measurement of the oleocanthal and oleacein levels in
      olive oil by quantitative (1)H NMR was developed. The method was applied to the
      study of 175 monovarietal commercial Greek and California olive oil samples. The
      main findings were as follows: (1) There was a significant variation concerning
      the concentrations of oleocanthal and oleacein among the studied samples. Their
      concentrations ranged from nondetectable to 355 mg/kg and their sum (index D1)
      from 0 to 501 mg/kg. (2) There are olive varieties that independent of geographic
      origin and harvest time produce oil that contains both compounds in low levels.
      (3) There is a positive correlation of a high level of oleocanthal and oleacein
      in olive oils with the early time of harvest. Although there is a need for more
      extensive study, a new index for the characterization of extra virgin olive oils,
      which is a combination of D1 = oleocanthal + oleacein level and D2 =
      oleocanthal/oleacein ratio, seems to be very useful.

PMID- 23116298
TI  - Exploring the mechanisms of alcohol-related damage in oral mucosa - is oxidative
      stress associated with the increase in cell proliferation in rat tongue
      epithelium?
AB  - CONTEXT: Alcohol consumption has been related to a cell proliferation increase in
      oral epithelium but its mechanism remains unclear. OBJECTIVE: The aim of this
      study was to investigate whether oxidative stress parameters are implicated in
      the induction of cell proliferation in rat tongue epithelium after different
      times of chronic alcohol consumption. MATERIALS AND METHODS: Cell proliferation
      was assessed in tongue epithelium using AgNOR (argyrophilic proteins related to
      active nucleolar organizer regions) quantification. Oxidative stress parameters
      [lipid peroxidation, protein carbonyls, superoxide dismutase activity and
      catalase (CAT) activity and immunocontent] and Nrf2 immunocontent were quantified
      in tongue homogenates. RESULTS AND DISCUSSION: Mean AgNOR numbers (mAgNOR) per
      nucleus was 2.22 +/- 0.30 in ventral tongue epithelium after 120 days of alcohol
      consumption (vs. 1.87 +/- 0.18 for control animals and 1.91 +/- 0.23 for animals
      treated with alcohol for 60 days) indicating cell proliferation increase (p <
      0.05, ANOVA followed by Tukey post hoc). Interestingly, 60 days of alcohol
      consumption induced changes in oxidative stress parameters, but no alteration in
      cell proliferation. Vitamin E co-treatment was conduced in order to evaluate its
      possible protective effects. The 120 day Tween + vitamin E + alcohol treatment
      induced an increase in mAgNORs when compared to the Tween + vitamin E treated
      group (respectively 2.10 +/- 0.30 vs. 1.77 +/- 0.11, p < 0.05, ANOVA followed by
      Tukey post hoc), showing that vitamin E co-treatment had no protective effects.
      In addition, an inverse association was observed between CAT activity and AgNORs
      quantity (R = -0.32; p < 0.05, Person's correlation) as well as the possible
      involvement of Nrf2 in alcohol-related damage. CONCLUSIONS: Our findings suggest
      that the increase in cell proliferation associated with alcohol-related damage
      has no direct relation with an imbalance in oxidative parameters. In contrast,
      our results indicate that hydrogen peroxide may be implicated in cellular
      signaling during proliferation in the oral mucosa.

PMID- 23116299
TI  - Cross-fostering eggs reveals that female collared flycatchers adjust clutch sex
      ratios according to parental ability to invest in offspring.
AB  - Across animal taxa, reproductive success is generally more variable and more
      strongly dependent upon body condition for males than for females; in such cases,
      parents able to produce offspring in above-average condition are predicted to
      produce sons, whereas parents unable to produce offspring in good condition
      should produce daughters. We tested this hypothesis in the collared flycatcher
      (Ficedula albicollis) by cross-fostering eggs among nests and using the condition
      of foster young that parents raised to fledging as a functional measure of their
      ability to produce fit offspring. As predicted, females raising heavier-than
      average foster fledglings with their social mate initially produced male-biased
      primary sex ratios, whereas those raising lighter-than-average foster fledglings
      produced female-biased primary sex ratios. Females also produced male-biased
      clutches when mated to males with large secondary sexual characters (wing
      patches), and tended to produce male-biased clutches earlier within breeding
      seasons relative to females breeding later. However, females did not adjust the
      sex of individuals within their clutches; sex was distributed randomly with
      respect to egg size, laying order and paternity. Future research investigating
      the proximate mechanisms linking ecological contexts and the quality of offspring
      parents are able to produce with primary sex-ratio variation could provide
      fundamental insight into the evolution of context-dependent sex-ratio adjustment.

PMID- 23116300
TI  - A robust GC-MS/MS method for the determination of chlorothalonil in fruits and
      vegetables.
AB  - Chlorothalonil is a non-systemic fungicide that is easily degraded in contact
      with plants and soil or even by the effect of light and pH. A method for the
      determination of chlorothalonil in courgettes, strawberries, oranges, leeks and
      tomato by solvent extraction followed by GC-MS/MS with a triple quadrupole
      analyser was developed. The causes of chlorothalonil degradation during sample
      treatment were studied and minimised. The final method was based on extraction
      with acetone in the presence of 0.1 M EDTA sodium salt solution, and clean-up by
      SPE using OASIS HLB cartridges. Isotope-labelled hexachlorobenzene (HCB-(13)C(6))
      was added as an internal standard to the SPE extracts before analysis by GC-MS/MS
      (EI) (QqQ) analysis in order to correct for instrumental deviations.
      Quantification was performed by matrix-matched standard calibration using
      relative responses to the internal standard. Two MS/MS transitions were used for
      mass spectrometric determination of chlorothalonil to ensure reliable
      quantification and confirmation. The method was validated using blank samples
      (for all matrices) spiked at two levels. Recoveries between 77% and 110% and an
      RSD below 20% were obtained for 0.1 and 0.01 mg kg(-1) spiking levels (n = 5).
      The validated method was applied to treated and untreated samples collected from
      an experimental field where a chlorothalonil formulated was applied.

PMID- 23116301
TI  - Hedgehog pathway inhibitors - current status and future prospects.
AB  - The Hedgehog (Hh) proteins comprise a group of secreted proteins that regulate
      cell growth, differentiation and survival. Inappropriate activation of the Hh
      signaling pathway has been implicated in the development of a variety of cancers.
      Hedgehog pathway inhibitors are a relatively new class of therapeutic agents that
      act by targeting the proteins involved in the regulation of Hh pathway (PTCH, SMO
      and Gli). Together, they serve as exciting new prospects, with a bright future,
      both alone or as an adjuvant to the more traditional anti-cancer drugs.

PMID- 23116302
TI  - Noninvasive optical characterization of muscle blood flow, oxygenation, and
      metabolism in women with fibromyalgia.
AB  - INTRODUCTION: Women with fibromyalgia (FM) have symptoms of increased muscular
      fatigue and reduced exercise tolerance, which may be associated with alterations
      in muscle microcirculation and oxygen metabolism. This study used near-infrared
      diffuse optical spectroscopies to noninvasively evaluate muscle blood flow, blood
      oxygenation and oxygen metabolism during leg fatiguing exercise and during arm
      arterial cuff occlusion in post-menopausal women with and without FM. METHODS:
      Fourteen women with FM and twenty-three well-matched healthy controls
      participated in this study. For the fatiguing exercise protocol, the subject was
      instructed to perform 6 sets of 12 isometric contractions of knee extensor
      muscles with intensity steadily increasing from 20 to 70% maximal voluntary
      isometric contraction (MVIC). For the cuff occlusion protocol, forearm arterial
      blood flow was occluded via a tourniquet on the upper arm for 3 minutes. Leg or
      arm muscle hemodynamics, including relative blood flow (rBF), oxy- and deoxy
      hemoglobin concentration ([HbO2] and [Hb]), total hemoglobin concentration (THC)
      and blood oxygen saturation (StO2), were continuously monitored throughout
      protocols using a custom-built hybrid diffuse optical instrument that combined a
      commercial near-infrared oximeter for tissue oxygenation measurements and a
      custom-designed diffuse correlation spectroscopy (DCS) flowmeter for tissue blood
      flow measurements. Relative oxygen extraction fraction (rOEF) and oxygen
      consumption rate (rVO2) were calculated from the measured blood flow and
      oxygenation data. Post-manipulation (fatiguing exercise or cuff occlusion)
      recovery in muscle hemodynamics was characterized by the recovery half-time, a
      time interval from the end of manipulation to the time that tissue hemodynamics
      reached a half-maximal value. RESULTS: Subjects with FM had similar hemodynamic
      and metabolic response/recovery patterns as healthy controls during exercise and
      during arterial occlusion. However, tissue rOEF during exercise in subjects with
      FM was significantly lower than in healthy controls, and the half-times of
      oxygenation recovery (Delta[HbO2] and Delta[Hb]) were significantly longer
      following fatiguing exercise and cuff occlusion. CONCLUSIONS: Our results suggest
      an alteration of muscle oxygen utilization in the FM population. This study
      demonstrates the potential of using combined diffuse optical spectroscopies
      (i.e., NIRS/DCS) to comprehensively evaluate tissue oxygen and flow kinetics in
      skeletal muscle.

PMID- 23116304
TI  - Paper-based enzyme immobilization for flow injection electrochemical biosensor
      integrated with reagent-loaded cartridge toward portable modular device.
AB  - Paper-based enzyme immobilization for a flow injection electrochemical biosensor
      integrated with a reagent-loaded cartridge toward a portable device was
      developed. A paper disk was immobilized with enzyme, then it was integrated in a
      flow cell as an electrochemical biosensor. A silicon tube reagent-loaded
      cartridge was integrated into the system, a complicated procedure was simplified
      as a one-click operation toward development for point-of-care applications. In
      this research, glucose oxidase (GOx) was employed as a model enzyme, silver ion
      as an inhibition reagent for GOx, and EDTA as a regeneration reagent. When GOx
      was inhibited by silver ions, glucose was introduced for electrochemical
      measurements before and after inhibited enzyme regeneration and the difference
      was caused by silver inhibition. The modular device has great potential for other
      applications, e.g., detection of enzyme activity and substrate. The platform
      based on double-test mode provided accurate results due to elimination of an
      average or control value in comparison with classical routine approaches.

PMID- 23116305
TI  - Diagnostic utility of direct immunofluorescence findings around hair follicles
      and sweat glands in immunobullous disease.
AB  - BACKGROUND: Inherent to some immunobullous disorders is potential for
      intraepidermal or dermal-epidermal junction fragility, a phenomenon that may
      compromise biopsy specimen integrity and direct immunofluorescence (DIF)
      interpretation. In these situations, cutaneous adnexal structures (e.g. hair
      follicles, sweat apparatus) usually remain intact. Whether periadnexal DIF
      findings are reliable in diagnosing immunobullous conditions is unknown. METHODS:
      We evaluated 56 cutaneous specimens with diagnostic immunoglobulin (Ig)
      deposition patterns that contained adnexal structures. In a corollary study, we
      examined 145 hematoxylin-eosin-stained frozen specimens to determine biopsy
      factors associated with the presence of adnexal structures. RESULTS: Periadnexal
      DIF findings offered diagnostic sensitivity in conditions with linear or cell
      surface Ig deposition or lupus band. Periadnexal DIF findings were unreliable in
      dermatitis herpetiformis. Biopsy specimens from scalp and genitalia were most
      likely to contain folliculosebaceous units and sweat duct apparatus,
      respectively. Relative depth of biopsy correlated directly with the likelihood of
      identifying sweat duct apparatus but not folliculosebaceous units. CONCLUSIONS:
      Periadnexal DIF findings may add diagnostic sensitivity in DIF evaluation of
      pemphigoid, pemphigus and lupus erythematosus. Pathologists can guide clinicians
      to biopsy certain anatomic sites and to obtain sufficient biopsy depth to
      increase the probability of capturing adnexal structures and, therefore,
      diagnostic yield from DIF specimens.

PMID- 23116303
TI  - Beneficial 'unintended effects' of a cereal cystatin in transgenic lines of
      potato, Solanum tuberosum.
AB  - BACKGROUND: Studies reported unintended pleiotropic effects for a number of
      pesticidal proteins ectopically expressed in transgenic crops, but the nature and
      significance of such effects in planta remain poorly understood. Here we assessed
      the effects of corn cystatin II (CCII), a potent inhibitor of C1A cysteine (Cys)
      proteases considered for insect and pathogen control, on the leaf proteome and
      pathogen resistance status of potato lines constitutively expressing this
      protein. RESULTS: The leaf proteome of lines accumulating CCII at different
      levels was resolved by 2-dimensional gel electrophoresis and compared with the
      leaf proteome of a control (parental) line. Out of ca. 700 proteins monitored on
      2-D gels, 23 were significantly up- or downregulated in CCII-expressing leaves,
      including 14 proteins detected de novo or up-regulated by more than five-fold
      compared to the control. Most up-regulated proteins were abiotic or biotic stress
      responsive proteins, including different secretory peroxidases, wound inducible
      protease inhibitors and pathogenesis-related proteins. Accordingly, infection of
      leaf tissues by the fungal necrotroph Botryris cinerea was prevented in CCII
      expressing plants, despite a null impact of CCII on growth of this pathogen and
      the absence of extracellular Cys protease targets for the inhibitor. CONCLUSIONS:
      These data point to the onset of pleiotropic effects altering the leaf proteome
      in transgenic plants expressing recombinant protease inhibitors. They also show
      the potential of these proteins as ectopic modulators of stress responses in
      planta, useful to engineer biotic or abiotic stress tolerance in crop plants of
      economic significance.

PMID- 23116306
TI  - Antimycobacterial activity of quaternary pyridinium salts and pyridinium N-oxides
      -review.
AB  - The treatment of tuberculosis and other mycobacterioses is still a major world
      health problem and new antimycobacterial compounds unrelated to approved drugs
      are in demand. Quaternary ammonium salts have revealed many usable properties
      especially as antimicrobials; they are widely used as disinfection and antiseptic
      agents. Some of these compounds, including pyridinium salts, have revealed
      substantial antimycobacterial action, although the presence of the cationic
      nitrogen itself is not sufficient for activity. A long Nalkyl chain is also not
      necessary for antimycobacterial activity, although it is associated with improved
      activity. Compounds that have shown significant in vitro activity, e.g.,
      cetylpyridinium, N-(substituted alkyl)pyridinium salts, 3-[(5-
      cyclopentylpentyl)(substituted phenyl)amino]-1-methylpyridinium iodides or
      pyridinium alkyl ethers of steroids (good activity with minimum inhibitory
      concentrations - MIC from 0.4 MUg/mL). However, most pyridinium salts have mild
      or moderate activity against fastand/ or slow-growing mycobacteria, including N
      methylated isoniazids or pyridinium-based oximes. Moreover, a pyridinium ring is
      present in some cefalosporines (e.g., cefaloridine, ceftazidime and cefsulodine)
      with antimycobacterial properties. The N-oxidation of pyridine mostly resulted in
      retained or increased minimum inhibitory concentrations. Additionally, the action
      of pyridinium N-oxides against mycobacteria is not especially robust. The
      mechanism of action of pyridinium compounds remains elusive, but the inhibition
      of some mycobacterial enzymes has been described for a few derivatives.

PMID- 23116307
TI  - Advances in clinical study of curcumin.
AB  - Curcumin has been estimated as a potential agent for many diseases and attracted
      great attention owing to its various pharmacological activities, including anti
      cancer, and anti-inflammatory. Now curcumin is being applied to a number of
      patients with breast cancer, rheumatoid arthritis, Alzheimer's disease,
      colorectal cancer, psoriatic, etc. Several clinical trials have stated that
      curcumin is safe enough and effective. The objective of this article was to
      summarize the clinical studies of curcumin, and give a reference for future
      studies.

PMID- 23116308
TI  - Recent progress in studying curcumin and its nano-preparations for cancer
      therapy.
AB  - A hydrophobic polyphenol compound extracted from turmeric, curcumin has been
      widely utilized as traditional medicines for centuries in China and India. Over
      the last decades, because of its low toxicity, extensive studies have been
      focused on its physicochemical properties and pharmacological activities on
      various diseases, such as cancer, cardio-vascular disease, inflammatory bowel,
      wound healing, Alzheimer's disease, rheumatoid arthritis, and diabetes. In
      particular, bioactivities of curcumin as an effective chemopreventive agent,
      chemo-/radio-sensitizer for tumor cells, and chemo-/radio-protector for normal
      organs, are of extraordinary research interests in the literature. Despite these
      advantages, applications of curcumin are limited in clinical trials because of
      its poor water solubility and low oral bioavailability. Nano-preparations as an
      emerging platform for the efficient delivery of anti-cancer drugs should overcome
      these problems. In this review, we at first briefly revisit important properties
      of curcumin as well as its uses in cancer treatments, and then overview various
      nano-preparations of curcumin for cancer therapy, including nanoparticles,
      liposomes, micelles, nanoemulsions, cyclodextrin complexes, nanodisks,
      nanofibres, solid lipid nanoparticles, and curcumin conjugates.

PMID- 23116310
TI  - The clinical applications of curcumin: current state and the future.
AB  - Curcumin is a natural polyphenol product derived from the rhizome of the Curcuma
      longa. In vivo and in vitro studies have uncovered many important bioactivities
      of curcumin, such as antioxidant activity, inducing cell apoptosis, inhibiting
      cell proliferation, anti-cell adhesion and motility, anti-angiogenesis and anti
      microbe properties. Based on these functions, curcumin has been used in clinical
      trials on various inflammatory diseases and cancers. In the future, it will be
      necessary to focus attention partly on the clinical application of curcumin in
      neurodegenerative diseases, cardiovascular diseases and diabetes, because many
      experiments have clarified the potential value of curcumin in these areas. As a
      diet-derived agent, curcumin has no severe toxicity except for minor
      gastrointestinal side effects even up to the dosage of 8 grams for 3 months.
      However, curcumin has a low systemic bioavailability, so it is imperative to
      improve the bioavailability of curcumin in its clinical application. Many
      methods, such as adjuvant drug delivery system and structural modification have
      been demonstrated to have a potential effect.

PMID- 23116311
TI  - A review of therapeutic effects of curcumin.
AB  - There is a growing interest in herbal medicine. Scientific studies have
      demonstrated the beneficial pharmacological effects of curcumin. Curcumin is a
      bright yellow spice, derived from the rhizome of Curcuma longa Linn. It has been
      proven that curcumin is a highly pleiotropic molecule which can be a modulator of
      intracellular signaling pathways that control cell growth, inflammation, and
      apoptosis. Curcumin might be a potential candidate for the prevention and/or
      treatment of some diseases due to its anti-oxidant, antiinflammatory activities
      and an excellent safety profile. We present an updated concise review of
      currently available animal and clinical studies demonstrating the therapeutic
      effect of curcumin.

PMID- 23116309
TI  - Curcumin nanomedicine: a road to cancer therapeutics.
AB  - Cancer is the second leading cause of death in the United States. Conventional
      therapies cause widespread systemic toxicity and lead to serious side effects
      which prohibit their long term use. Additionally, in many circumstances tumor
      resistance and recurrence is commonly observed. Therefore, there is an urgent
      need to identify suitable anticancer therapies that are highly precise with
      minimal side effects. Curcumin is a natural polyphenol molecule derived from the
      Curcuma longa plant which exhibits anticancer, chemopreventive, chemo- and radio
      sensitization properties. Curcumin's widespread availability, safety, low cost
      and multiple cancer fighting functions justify its development as a drug for
      cancer treatment. However, various basic and clinical studies elucidate
      curcumin's limited efficacy due to its low solubility, high rate of metabolism,
      poor bioavailability and pharmacokinetics. A growing list of nanomedicine(s)
      using first line therapeutic drugs have been approved or are under consideration
      by the Food and Drug Administration (FDA) to improve human health. These
      nanotechnology strategies may help to overcome challenges and ease the
      translation of curcumin from bench to clinical application. Prominent research is
      reviewed which shows that advanced drug delivery of curcumin (curcumin
      nanoformulations or curcumin nanomedicine) is able to leverage therapeutic
      benefits by improving bioavailability and pharmacokinetics which in turn improves
      binding, internalization and targeting of tumor(s). Outcomes using these novel
      drug delivery systems have been discussed in detail. This review also describes
      the tumor-specific drug delivery system(s) that can be highly effective in
      destroying tumors. Such new approaches are expected to lead to clinical trials
      and to improve cancer therapeutics.

PMID- 23116314
TI  - Curcumin: from chemistry to chemistry-based functions.
AB  - Curcumin is a yellow pigment found in the spice turmeric and a main functional
      constituent of the rhizomes of Curcuma longa. The multi-functionality of curcumin
      has recently attracted much attention in various fields, including food,
      medicinal, and clinical industries. Three major curcuminoids, curcumin,
      demethoxycurcumin, and bis-demethoxycurcumin, are distributed in not only
      Curcuma, but also the Zingiber species; however, distribution of other
      curcuminoids is very limited in nature. The radical scavenging ability of
      curcumin, which is the basis of medicinal functionality, is its most important
      property. Herein, the structures of several rare curcuminoids that have been
      identified during the past four decades are summarized. Mechanistic studies of
      the radical trapping stage of curcumin are also comprehensively reviewed, and the
      studies on antioxidant effects derived from this radical trapping ability of
      curcuminoids are discussed. Various chemical reactions of curcumin, such as photo
      oxidation, enzymatic oxidation, etc. are also summarized. In particular,
      antioxidation of curcumin in lipid media is introduced as a reaction unique to
      curcumin.

PMID- 23116313
TI  - Delivery of curcumin and medicinal effects of the copper(II)-curcumin complexes.
AB  - Curcumin, a yellow pigment extracted from the rhizome of Curcuma longa, commonly
      known as turmeric, is the most active agent of this herbal medicine. The
      therapeutic activities of curcumin are exemplified not only by its enhancement in
      wound healing but also in the treatment of inflammation, cystic fibrosis,
      Alzheimer's disease and cancer. There are two critical issues involving low
      aqueous stability and solubility that limit the bioavailability and application
      of curcumin as a therapeutic agent. To address these issues, delivery systems of
      curcumin including surfactant micelles, liposomes, polymer nanoparticles, casein
      micelles, plasma proteins and cyclodextrins have been developed and
      characterized. From a biochemical perspective, the medicinal activities of
      curcumin are proposed to be related to an elevated level of transition metals
      including copper, zinc and iron in many disease sites, especially those in cancer
      and Alzheimer's disease. Previous studies have demonstrated the importance of
      copper(II)-curcumin complexes in DNA damage owing to the strong interaction
      between curcumin and copper(II). Curcumin, as an anti-oxidant, possesses the
      abilities to scavenge radicals and maintain the levels of anti-oxidant enzymes in
      the presence of copper. On the other hand, copper(II)-curcumin complexes show pro
      oxidant effects by generating reactive oxygen species at a high free copper level
      in a reducing environment. This condition results in DNA damage and inhibition of
      vital signaling pathways in cancer cells, leading to apoptosis. In short,
      curcumin has dual roles as an anti-oxidant and a prooxidant in the presence of
      copper and these fascinating phenomena contribute greatly to its multiple
      medicinal effects.

PMID- 23116315
TI  - Chemical and structural features influencing the biological activity of curcumin.
AB  - Curcumin, a polyphenolic natural product, exhibits therapeutic activity against a
      number of diseases, attributed mainly to its chemical structure and unique
      physical, chemical, and biological properties. It is a diferuloyl methane
      molecule [1,7-bis (4-hydroxy-3- methoxyphenyl)-1,6-heptadiene-3,5-dione)]
      containing two ferulic acid residues joined by a methylene bridge. It has three
      important functionalities: an aromatic o-methoxy phenolic group, alpha, beta
      unsaturated beta-diketo moiety and a seven carbon linker. Extensive research in
      the last two decades has provided evidence for the role of these different
      functional groups in its crucial biological activities. A few highlights of
      chemical structural features associated with the biological activity of curcumin
      are: The o-methoxyphenol group and methylenic hydrogen are responsible for the
      antioxidant activity of curcumin, and curcumin donates an electron/ hydrogen atom
      to reactive oxygen species. Curcumin interacts with a number of biomolecules
      through non-covalent and covalent binding. The hydrogen bonding and
      hydrophobicity of curcumin, arising from the aromatic and tautomeric structures
      along with the flexibility of the linker group are responsible for the non
      covalent interactions. The alpha, beta-unsaturated beta-diketone moiety
      covalently interacts with protein thiols, through Michael reaction. The beta
      diketo group forms chelates with transition metals, there by reducing the metal
      induced toxicity and some of the metal complexes exhibit improved antioxidant
      activity as enzyme mimics. New analogues with improved activity are being
      developed with modifications on specific functional groups of curcumin. The
      physico-chemical and structural features associated with some of the biological
      activities of curcumin and important analogues are summarized in this article.

PMID- 23116312
TI  - Perspectives on new synthetic curcumin analogs and their potential anticancer
      properties.
AB  - Curcumin is the active component of dried rhizome of Curcuma longa, a perennial
      herb belonging to ginger family, cultivated extensively in south and southeastern
      tropical Asia. It is widely consumed in the Indian subcontinent, south Asia and
      Japan in traditional food recipes. Extensive research over last few decades has
      shown that curcumin is a potent anti-inflammatory agent with powerful therapeutic
      potential against a variety of cancers. It suppresses proliferation and
      metastasis of human tumors through regulation of various transcription factors,
      growth factors, inflammatory cytokines, protein kinases and other enzymes. It
      induces apoptotic cell death and also inhibits proliferation of cancer cells by
      cell cycle arrest. Pharmacokinetic data has shown that curcumin undergoes rapid
      metabolism leading to glucuronidation and sulfation in the liver and excretion in
      the feces, which accounts for its poor systemic bioavailability. The compound
      has, therefore, been formulated and administered using different drug delivery
      systems such as liposomes, micelles, polysaccharides, phospholipid complexes and
      nanoparticles that can overcome the limitation of bioavailability to some extent.
      Attempts to avoid rapid metabolism of curcumin until now have been met with
      limited success. This has prompted researchers to look for new synthetic curcumin
      analogs in order to overcome the drawbacks of limited bioavailability and rapid
      metabolism, and gain efficacy with reduced toxicity. In this review we provide a
      summarized account of novel synthetic curcumin formulations and analogs, and the
      recent progress in the field of cancer prevention and treatment.

PMID- 23116316
TI  - Antioxidant and antiinflammatory activities of curcumin on diabetes mellitus and
      its complications.
AB  - Diabetes mellitus (DM) has reached pandemic status and shows no signs of
      abatement. It can severely impair people's quality of life and affects patients
      all over the world. Since it is a serious, chronic metabolic disease, it can
      bring about many kinds of complications, which can in turn increase mortality. In
      recent decades, more and more studies have shown that oxidative stress and
      inflammatory reactions play critical roles in the pathogenesis of DM. There is an
      increasing demand for natural antidiabetic medicines that do not have the same
      side effects as modern drugs. Curcumin, a phytochemical found in the spice
      turmeric, has been used in India for centuries, and it has no known side effects.
      It has been shown to have some beneficial effects against various chronic
      illnesses. Many of these therapeutic actions can be attributed to its potent anti
      oxidant and anti-inflammatory activities. In view of the oxidative stress and
      inflammatory mechanisms of DM, curcumin can be considered suitable for the
      prevention and amelioration of diabetes. In this review, we summarize the
      nosogenesis of DM, giving primary focus to oxidative stress and inflammation. We
      discuss the anti-oxidant and anti-inflammatory activities of curcumin in DM and
      its ability to mitigate the effects on DM and its associated complications in
      detail.

PMID- 23116317
TI  - Promising curcumin-based drug design: mono-carbonyl analogues of curcumin (MACs).
AB  - Curcumin exhibits a surprisingly wide range of chemo-preventive and chemo
      therapeutic activities. Curcumin has undergone more than 40 clinical trials for
      the treatment of inflammatory diseases and various human cancers. However, phase
      I/II clinical trials have shown that curcumin exhibit poor bioavailability in
      humans. Major reasons resulting in the low plasma and tissue levels of curcumin
      appear to be its poor absorption, fast metabolism, and rapid systemic
      elimination. It is suggested that the beta-diketone moiety is responsible for the
      instability and weak pharmacokinetic profiles of curcumin. To attenuate the fast
      metabolism of curcumin, numerous approaches have been considered, including the
      adjuvant, the liposomal curcumin, curcumin nanoparticles and phospholipid
      complex, and structural modification to prepare the analogues without the beta
      diketone moiety. Particularly, the latter called mono-carbonyl analogs of
      curcumin (MACs) has been reported to has an enhanced stability in vitro and an
      improved pharmacokinetic profile in vivo. Thus, MACs have attracted a high
      attention for development of new curcumin-based agents with both enhanced
      bioactivities and pharmacokinetic profiles. A number of MACs have shown potential
      anticancer and anti-inflammatory activity in various models. Several of them have
      been studied intensively in order to develop novel agents. This review covers 607
      MACs as well as their biological activities reported in the past two decades.

PMID- 23116318
TI  - Recent progress and novel insights in curcumin research "from chemistry to
      clinical use".

PMID- 23116319
TI  - Molecular dynamics simulation of amorphous indomethacin.
AB  - Molecular dynamics (MD) simulations have been conducted using an assembly
      consisting of 105 indomethacin (IMC) molecules and 12 water molecules to
      investigate the underlying dynamic (e.g., rotational and translational
      diffusivities and conformation relaxation rates) and structural properties (e.g.,
      conformation, hydrogen-bonding distributions, and interactions of water with IMC)
      of amorphous IMC. These properties may be important in predicting physical
      stability of this metastable material. The IMC model was constructed using X-ray
      diffraction data with the force-field parameters mostly assigned by analogy with
      similar groups in Amber-ff03 and atomic charges calculated with the
      B3LYP/ccpVTZ30, IEFPCM, and RESP models. The assemblies were initially
      equilibrated in their molten state and cooled through the glass transition
      temperature to form amorphous solids. Constant temperature dynamic runs were then
      carried out above and below the T(g) (i.e., at 600 K (10 ns), 400 K (350 ns), and
      298 K (240 ns)). The density (1.312 +/- 0.003 g/cm(3)) of the simulated amorphous
      solid at 298 K was close to the experimental value (1.32 g/cm(3)) while the
      estimated T(g) (384 K) was ~64 degrees higher than the experimental value (320 K)
      due to the faster cooling rate. Due to the hindered rotation of its amide bond,
      IMC can exist in different diastereomeric states. Different IMC conformations
      were sufficiently sampled in the IMC melt or vapor, but transitions occurred
      rarely in the glass. The hydrogen-bonding patterns in amorphous IMC are more
      complex in the amorphous state than in the crystalline polymorphs. Carboxylic
      dimers that are dominant in alpha- and gamma-crystals were found to occur at a
      much lower probability in the simulated IMC glasses while hydrogen-bonded IMC
      chains were more easily identified patterns in the simulated amorphous solids. To
      determine molecular diffusivity, a novel analytical method is proposed to deal
      with the non-Einsteinian behavior, in which the temporal evolution of the
      apparent diffusivity D(t) is described by a relaxation model such as the KWW
      function and extrapolated to infinite time. The diffusion coefficient found for
      water diffusing in amorphous indomethacin at 298 K (2.7 * 10(-9) cm(2)/s)
      compares favorably to results obtained in experimental IMC glasses (0.9-2.0 * 10(
      9) cm(2)/s) and is mechanistically associated with beta-relaxation processes that
      are dominant in sub-T(g) glasses.

PMID- 23116320
TI  - Identifying the evidence-base for art-based practices and their potential benefit
      for mental health recovery: a critical review.
AB  - PURPOSE: Art-based practices show promise as a beneficial solution for mental
      health services because they are in line with the whole person recovery framework
      currently being adopted, and have high acceptability with consumers.
      Nevertheless, incorporation of art-based approaches into mental health services
      has been impeded by claims of an insufficient evidence-base and ongoing debates
      about the most suitable research practices. This article addresses this gap in
      the literature by critically reviewing current research on the benefits of art
      based practices in mental health rehabilitation settings. METHOD: A critical
      review of previous research was conducted identifying all quantitative,
      qualitative and mixed method studies that addressed art making and adult mental
      illness. Then a deductive/theoretical thematic analysis was conducted using Lal's
      framework for conceptualising mental health recovery. RESULTS: The identified
      areas where art-based practices were of key benefit included psychological and
      social recovery, particularly in the areas of self-discovery, self-expression,
      relationships and social identity. These findings in conjunction with the
      identified benefits to clinical, occupational and contextual recovery indicate
      that art-based practices play a substantial role in mental health recovery. To
      add weight to these claims, future research endeavours need to integrate the
      suggested recommendations detailed in this review. CONCLUSION: Recommendations
      are made to improve the quality of future research, including the need for well
      designed mixed-method studies that integrate qualitative and quantitative
      research, whilst keeping in mind the values of mental heath recovery, would
      further validate this current evidence-base.

PMID- 23116321
TI  - Key roles of the downstream mobile jaw of Escherichia coli RNA polymerase in
      transcription initiation.
AB  - Differences in kinetics of transcription initiation by RNA polymerase (RNAP) at
      different promoters tailor the pattern of gene expression to cellular needs.
      After initial binding, large conformational changes occur in promoter DNA and
      RNAP to form initiation-capable complexes. To understand the mechanism and
      regulation of transcription initiation, the nature and sequence of these
      conformational changes must be determined. Escherichia coli RNAP uses binding
      free energy to unwind and separate 13 base pairs of lambdaP(R) promoter DNA to
      form the unstable open intermediate I(2), which rapidly converts to much more
      stable open complexes (I(3), RP(o)). Conversion of I(2) to RP(o) involves
      folding/assembly of several mobile RNAP domains on downstream duplex DNA. Here,
      we investigate effects of a 42-residue deletion in the mobile beta' jaw
      (DeltaJAW) and truncation of promoter DNA beyond +12 (DT+12) on the steps of
      initiation. We find that in stable DeltaJAW open complexes the downstream
      boundary of hydroxyl radical protection shortens by 5-10 base pairs, as compared
      to wild-type (WT) complexes. Dissociation kinetics of open complexes formed with
      DeltaJAW RNAP and/or DT+12 DNA resemble those deduced for the structurally
      uncharacterized intermediate I(3). Overall rate constants (k(a)) for promoter
      binding and DNA opening by DeltaJAW RNAP are much smaller than for WT RNAP.
      Values of k(a) for WT RNAP with DT+12 and full-length lambdaP(R) are similar,
      though contributions of binding and isomerization steps differ. Hence, the jaw
      plays major roles both early and late in RP(o) formation, while downstream DNA
      functions primarily as the assembly platform after DNA opening.

PMID- 23116322
TI  - Rapid T-cell chimerism switch and memory T-cell expansion are associated with pre
      engraftment immune reaction early after cord blood transplantation.

PMID- 23116323
TI  - Long-term treatment acceptance: what is it, and how can it be assessed?
AB  - BACKGROUND: Understanding the link between patients' beliefs and behavior may
      help explain their attitude to their treatment. How patients' personal experience
      of their treatment results in their decision to accept taking it or not and to
      persist in taking it remains to be explored more thoroughly. Acceptance is
      hypothesized to be the balance patients establish between their medication's
      advantages and its disadvantages, based on their personal experience with the
      medication. Measuring patients' acceptance of their medication is likely to
      predict their behavior (adherence and persistence) towards their treatment.
      OBJECTIVE: Our objective was to develop a generic medication acceptance measure
      assessing how patients weigh advantages and disadvantages of long-term
      medications. METHODS: A literature review was conducted using keywords related to
      acceptance, perceptions, motivations, and barriers linked to treatment.
      Exploratory interviews were performed with five pharmacists and 19 patients.
      Interviews were systematically analyzed in order to complete the initial
      conceptual model. Questionnaire items were generated for each concept identified,
      using patients' words. The resulting test version was tested for relevance and
      comprehension with six patients and revised accordingly; the new version was
      tested on a second set of five patients and revised to create the pilot version
      of the questionnaire. RESULTS: Items generated for each concept identified were
      organized into six domains: drug characteristics, duration, constraints, side
      effects, efficacy, and global acceptance of treatment. Except for a few items
      that were modified or deleted following patients' suggestions and some minor
      modifications in the answer choices, the questionnaire was globally well
      accepted, easy to complete, and considered relevant and appropriate by patients.
      The pilot version of the ACCEPT(c) questionnaire contains 32 questions divided
      into the same six domains as the test version. CONCLUSIONS: The existence of the
      hypothesized concept of medication acceptance was confirmed. The ACCEPT(c)
      questionnaire will allow assessment of the acceptance of a wide range of long
      term medications based on patient experience. Further study will examine how well
      this measure predicts and explains adherence to these medications.

PMID- 23116324
TI  - Evaluating the use of fluorescent imaging for the quantification of dental
      fluorosis.
AB  - BACKGROUND: The quantification of fluorosis using fluorescence imaging (QLF)
      hardware and stain analysis software has been demonstrated in selected
      populations with good correlation between fluorescent image metrics and TF Index
      scores from photographs. The aim of this study was to evaluate the ability of QLF
      to quantify fluorosis in a population of subjects (aged 11-13) participating in
      an epidemiological caries and fluorosis survey in fluoridated and non-fluoridated
      communities in Northern England. METHODS: Fluorescent images of the maxillary
      incisors were captured together with standardized photographs were scored blind
      for fluorosis using the TF Index. Subjects were excluded from the analysis if
      there were restorations or caries on the maxillary central incisors. RESULTS:
      Data were available for 1774 subjects (n=905 Newcastle, n=869 Manchester). The
      data from the fluorescence method demonstrated a significant correlation with TF
      Index scores from photographs (Kendall's tau = 0.332 p<0.0001). However, a number
      of additional confounding factors such as the presence of extrinsic stain or
      increased enamel translucency on some subjects without fluorosis or at low levels
      of fluorosis severity had an adverse impact on tooth fluorescence and hence the
      outcome variable. This in conjunction with an uneven distribution of subjects
      across the range of fluorosis presentations may have resulted in the lower than
      anticipated correlations between the fluorescent imaging metrics and the
      photographic fluorosis scores. Nevertheless, the fluorescence imaging technique
      was able to discriminate between a fluoridated and non-fluoridated population
      (p<0.001). CONCLUSIONS: Despite confounding factors the fluorescence imaging
      system may provide a useful objective, blinded system for the assessment of
      enamel fluorosis when used adjunctively with photographic scoring.

PMID- 23116325
TI  - Randomized controlled trial comparing highly purified (HP-hCG) and recombinant
      hCG (r-hCG) for triggering ovulation in ART.
AB  - BACKGROUND: A randomized controlled trial (RCT) comparing highly purified human
      Choriogonadotrophin (HP-hCG) and recombinant hCG (r-hCG) both administered
      subcutaneously for triggering ovulation in controlled ovarian stimulation (COS)
      for Assisted Reproductive Technology (ART). METHODS: Multi-centre (n = 4),
      prospective, controlled, randomized, non-inferiority, parallel group,
      investigator blind design, including 147 patients. The trial was registered with
      www.clinicaltrials.gov, using the identifier: NCT00335569. The primary endpoint
      is the number of oocytes retrieved, while the secondary endpoints include embryo
      implantation, pregnancy and delivery rates as well as safety parameters. RESULTS:
      The number of retrieved oocytes was not inferior when HP-hCG was used as compared
      to r-hCG: the mean number was 13.3 (6.8) in HP-hCG and 12.5 (5.8) in the r-hCG
      group (p = 0.49) with a 95% CI (-1.34, 2.77). Regarding the secondary outcomes,
      there were also no differences in fertilization rate at 57.3% (467/815) vs. 61.3%
      (482/787) (p = 0.11), the number of embryos available for transfer and
      cryopreservation (2PN stage) and implantation, pregnancy and delivery rates.
      Furthermore, there were no differences in the number and type of adverse events
      reported. HP-hCG was therefore not inferior to r-hCG. CONCLUSIONS: HP-hCG and r
      hCG are equally efficient and safe for triggering ovulation in ART and, both
      being administered subcutaneously, equally practical and well tolerated by
      patients.

PMID- 23116326
TI  - Clinicopathological features and malignant transformation of oral lichen planus:
      a 12-years retrospective study.
AB  - OBJECTIVE: Oral lichen planus (OLP) is known to be associated with the risk of
      developing oral squamous cell carcinoma (OSCC). The objective of this study was
      to investigate the clinicopathological features of OLP and the prevalence of
      malignant transformation in this setting. MATERIALS AND METHODS: This
      retrospective study was carried out on 204 medical records of patients with
      histologically proven OLP who received long-term follow-up (range 6 months-12
      years). Data were entered in an informatic database. The statistical analysis,
      when needed, was performed with the chi-squared test for significance (p < 0.05).
      RESULTS: At the moment of the diagnosis, out of 204 patients (163 female and 41
      male; mean age 54.5 years), 107 patients (52.45%) suffered from systemic chronic
      diseases, in particular 46 (22.5%) from hepatitis C. Clinically, the reticular
      form of OLP was the predominant one and most patients had multiple oral sites of
      involvement. Fourteen patients showed extra-oral lesions. A percentage of
      malignant transformation less than 1% was found. In fact, two patients (0.98%)
      underwent a malignant transformation at a site previously diagnosed as OLP.
      CONCLUSIONS: At present, OLP is accepted as being a potential malignant disorder,
      therefore lifelong follow-up is recommended.

PMID- 23116327
TI  - Chlorodifluoroacetyl isocyanate, ClF2CC(O)NCO: preparation and structural and
      spectroscopic studies.
AB  - Chlorodifluoroacetyl isocyanate, ClF2CC(O)NCO, was prepared by the reaction of
      ClF2CC(O)Cl with excess of AgNCO. The colorless compound melts at -83  degrees C
      and the vapor pressure follows the equation ln p = -3868.3 (1/T) + 10.89 (p
      [Atm], T [K]) in the range -38 to +22  degrees C, extrapolated bp ca. 82  degrees
      C. It has been characterized by IR (gas phase, Ar matrix), liquid Raman, 19F and
      13C NMR, gas UV-vis spectrum, photoelectron spectroscopy (PES), photoionization
      mass spectrometry (PIMS), and gas electron diffraction (GED). The matrix
      photochemistry has been studied and the conformational properties of ClF2CC(O)NCO
      have been analyzed by joint application of vibrational spectroscopy, GED, and
      quantum chemical calculations. Two conformers were detected in gaseous and liquid
      phases, in which the C-Cl bond adopts a gauche orientation with respect to the
      C?O group, whereas this group can be in syn or anti orientation with respect to
      the N?C bond of the NCO group. An enthalpy difference DeltaH(exp) degrees  = 1.3
      +/- 0.2 kcal mol(-1) between the most stable syn-gauche and the less stable anti
      gauche form was derived using the van't Hoff equation, which is in reasonable
      agreement with the computed difference of DeltaH degrees  = 0.8 kcal mol(-1)
      (B3LYP/6-311+G(3df) approximation). The most significant gas phase structural
      parameters for gauche-syn ClF2CC(O)NCO are r(e)(NC?O) = 1.157(1) A, r(e)(N?CO) =
      1.218(1) A, r(e)(N-C) = 1.378(9) A, r(e)(C?O) = 1.195(1) A, angle(e)(CNC) =
      128.6(19) degrees . Photolysis of ClF2CC(O)NCO using an ArF excimer laser (193
      nm) mainly yield ClF2CNCO along with some ClF2CC(O)N nitrene. The valence
      electronic properties of the title compound were studied using the PES and PIMS.
      The experimental first vertical ionization energy of 11.54 eV corresponds to the
      ejection of a carbonylic oxygen lone pair electron.

PMID- 23116328
TI  - Using administrative health data to identify individuals with intellectual and
      developmental disabilities: a comparison of algorithms.
AB  - BACKGROUND: Individuals with intellectual and developmental disabilities (IDD)
      experience high rates of physical and mental health problems; yet their health
      care is often inadequate. Information about their characteristics and health
      services needs is critical for planning efficient and equitable services. A
      logical source of such information is administrative health data; however, it can
      be difficult to identify cases with IDD in these data. The purpose of this study
      is to evaluate three algorithms for case finding of IDD in health administrative
      data. METHODS: The three algorithms were created following existing approaches in
      the literature which ranged between maximising sensitivity versus balancing
      sensitivity and specificity. The broad algorithm required only one IDD service
      contact across all available data and time periods, the intermediate algorithm
      added the restriction of a minimum of two physician visits while the narrow
      algorithm added a further restriction that the time period be limited to 2006
      onward. The resulting three cohorts were compared according to socio-demographic
      and clinical characteristics. Comparisons on different subgroups for a
      hypothetical population of 50,000 individuals with IDD were also carried out:
      this information may be relevant for planning specialised treatment or support
      programmes. RESULTS: The prevalence rates of IDD per 100 were 0.80, 0.52 and 0.18
      for the broad, intermediate and narrow algorithms, respectively. Except for
      'percentage with psychiatric co-morbidity', the three cohorts had similar
      characteristics (standardised differences < 0.1). More stringent thresholds
      increased the percentage of psychiatric co-morbidity and decreased the
      percentages of women and urban residents in the identified cohorts (standardised
      differences = 0.12 to 0.46). More concretely, using the narrow algorithm to
      indirectly estimate the number of individuals with IDD, a practice not uncommon
      in planning and policy development, classified nearly 7000 more individuals with
      psychiatric co-morbidities than using the intermediate algorithm. CONCLUSIONS:
      The prevalence rate produced by the intermediate algorithm most closely
      approximated the reported literature rate suggesting the value of imposing a two
      physician visit minimum but not restricting the time period covered. While the
      statistical differences among the algorithms were generally minor, differences in
      the numbers of individuals in specific population subgroups may be important
      particularly if they have specific service needs. Health administrative data can
      be useful for broad-based service planning for individuals with IDD and for
      population level comparisons around their access and quality of care.

PMID- 23116329
TI  - Comparative analysis of collagen type II-specific immune responses during
      development of collagen-induced arthritis in two B10 mouse strains.
AB  - INTRODUCTION: Immune responses against collagen type II (CII) are crucial for the
      development of collagen-induced arthritis (CIA). The aim of the present study was
      to evaluate and compare the CII-directed T cell and antibody specificity at
      different time points in the course of CIA using two mouse strains on the B10
      genetic background - B10.Q, expressing Aq MHC class II molecules, and
      B10.DR4.Ncf1*/*, expressing human rheumatoid arthritis-associated MHC II DR4
      molecules (DRA*0101/DRB*0401). METHODS: B10.Q and B10.DR4.Ncf1*/* mice were
      immunized with CII emulsified in adjuvant and development of CIA was assessed. T
      cells from draining lymph nodes were restimulated in vitro with CII peptides and
      interferon-gamma (IFN-gamma) levels in culture supernatants were evaluated by
      ELISA. CII-specific antibody levels in serum samples were measured by ELISA.
      RESULTS: At four different CIA time points we analyzed T cell specificity to the
      immunodominant CII epitope 259-273 (CII259-273) and several posttranslationally
      modified forms of CII259-273 as well as antibody responses to three B cell
      immunodominant epitopes on CII (C1, U1, J1). Our data show that CII-specific T
      and B cell responses increase dramatically after disease onset in both strains
      and are sustained during the disease course. Concerning anti-CII antibody fine
      specificity, during all investigated stages of CIA the B10.Q mice responded
      predominantly to the C1 epitope, whereas the B10.DR4.Ncf1*/* mice also recognized
      the U1 epitope. In the established disease phase, T cell reactivity toward the
      galactosylated CII259-273 peptide was similar between the DR4- and the Aq
      expressing strains whereas the response to the non-modified CII peptide was
      dramatically enhanced in the DR4 mice compared with the B10.Q. In addition, we
      show that the difference in the transgenic DR4-restricted T cell specificity to
      CII259-273 is not dependent on the degree of glycosylation of the collagen used
      for immunization. CONCLUSIONS: The present study provides important evaluation of
      CII-specific immune responses at different phases during CIA development as well
      as a comparative analysis between two CIA mouse models. We indicate significant
      differences in CII T cell and antibody specificities between the two strains and
      highlight a need for improved humanized B10.DR4 mouse model for rheumatoid
      arthritis.

PMID- 23116330
TI  - "Nonparametric Local Smoothing" is not image registration.
AB  - BACKGROUND: Image registration is one of the most important and universally
      useful computational tasks in biomedical image analysis. A recent article by Xing
      & Qiu (IEEE Transactions on Pattern Analysis and Machine Intelligence,
      33(10):2081-2092, 2011) is based on an inappropriately narrow conceptualization
      of the image registration problem as the task of making two images look alike,
      which disregards whether the established spatial correspondence is plausible. The
      authors propose a new algorithm, Nonparametric Local Smoothing (NLS) for image
      registration, but use image similarities alone as a measure of registration
      performance, although these measures do not relate reliably to the realism of the
      correspondence map. RESULTS: Using data obtained from its authors, we show
      experimentally that the method proposed by Xing & Qiu is not an effective
      registration algorithm. While it optimizes image similarity, it does not compute
      accurate, interpretable transformations. Even judged by image similarity alone,
      the proposed method is consistently outperformed by a simple pixel permutation
      algorithm, which is known by design not to compute valid registrations.
      CONCLUSIONS: This study has demonstrated that the NLS algorithm proposed recently
      for image registration, and published in one of the most respected journals in
      computer science, is not, in fact, an effective registration method at all. Our
      results also emphasize the general need to apply registration evaluation criteria
      that are sensitive to whether correspondences are accurate and mappings between
      images are physically interpretable. These goals cannot be achieved by simply
      reporting image similarities.

PMID- 23116331
TI  - School-based counseling using systematic feedback: a cohort study evaluating
      outcomes and predictors of change.
AB  - The outcomes of school-based counseling incorporating the Partners for Change
      Outcome Monitoring System (PCOMS) were evaluated using a cohort design, with
      multilevel modeling to identify predictors of change. Participants were 288 7-11
      year olds experiencing social, emotional or behavioral difficulties. The
      intervention was associated with significant reductions in psychological
      distress, with a pre-post effect size (d) of 1.49 on the primary outcome measure
      and 88.7% clinical improvement. Greater improvements were found for disabled
      children, older children, and where CBT methods were used. The findings provide
      support for the use of systematic feedback in therapy with children.

PMID- 23116332
TI  - Professor Isaac Kaplan: a tribute.

PMID- 23116334
TI  - Development and characterization of a field-deployable ion-trap mass spectrometer
      with an atmospheric pressure interface.
AB  - A field-deployable quadrupole ion-trap mass spectrometer with an atmospheric
      pressure interface is designed, built, and characterized. The instrument
      enclosure (48 cm * 43 cm * 42 cm) includes a roughing pump and a helium lecture
      bottle; the total weight of the instrument is 68 kg. Peak power consumption
      during the instrument operation is ~500 W. The instrument has a mass range of m/z
      30-2500, across which it provides better than unit mass resolution. The typical
      peak width at half height is 0.3 Th for a scan speed of 4000 Th/s. Operation of
      the instrument with electrospray and atmospheric-pressure matrix-assisted laser
      desorption ionization (AP-MALDI) ion sources is demonstrated. AP-MALDI analysis
      of low femtomole amounts of peptides reveals that the sensitivity of the
      instrument is on par with modern commercially available quadrupole ion-trap mass
      spectrometers. Tandem mass spectrometry capabilities of the instrument include
      simultaneous isolation and fragmentation of several different compounds. Two ways
      to reduce the size, weight, and power consumption of the portable instrument were
      explored, and results of these initial studies are presented. One of the ways
      includes utilization of hydrogen as a buffer gas for operation of the ion-trap
      mass analyzer in combination with a metal hydride method for storage of hydrogen
      in a compact rechargeable cartridge. Furthermore, careful selection of the inlet
      capillary dimensions allowed to eliminate the first "1 Torr" stage of the
      differential pumping without any significant loss of the instrument sensitivity.
      The elimination of this first pumping stage removed two turbo drag pumps, which
      substantially decreased the instrument's maximum power consumption (to ~300 W in
      peak use, and ~150 W during standby), as well as its size (to 30 cm * 43 cm * 50
      cm) and weight (to 35 kg).

PMID- 23116335
TI  - Cutaneous aspergillosis masquerading as Sweet's syndrome in a patient with acute
      myelogenous leukemia.

PMID- 23116333
TI  - The BLADE-ON-PETIOLE genes of Arabidopsis are essential for resistance induced by
      methyl jasmonate.
AB  - BACKGROUND: NPR1 is a gene of Arabidopsis thaliana required for the perception of
      salicylic acid. This perception triggers a defense response and negatively
      regulates the perception of jasmonates. Surprisingly, the application of methyl
      jasmonate also induces resistance, and NPR1 is also suspected to be relevant.
      Since an allelic series of npr1 was recently described, the behavior of these
      alleles was tested in response to methyl jasmonate. RESULTS: The response to
      methyl jasmonate of different npr1s alleles and NPR1 paralogs null mutants was
      measured by the growth of a pathogen. We have also tested the subcellular
      localization of some npr1s, along with the protein-protein interactions that can
      be measured in yeast. The localization of the protein in npr1 alleles does not
      affect the response to methyl jasmonate. In fact, NPR1 is not required. The genes
      that are required in a redundant fashion are the BOPs. The BOPs are paralogs of
      NPR1, and they physically interact with the TGA family of transcription factors.
      CONCLUSIONS: Some npr1 alleles have a phenotype in this response likely because
      they are affecting the interaction between BOPs and TGAs, and these two families
      of proteins are responsible for the resistance induced by methyl jasmonate in
      wild type plants.

PMID- 23116336
TI  - Validation of Terahertz coating thickness measurements using X-ray
      microtomography.
AB  - Terahertz pulsed imaging (TPI) is a recently developed nondestructive and
      noncontact method to measure the coating thickness of coated pharmaceutical
      tablets. The method requires no calibration in order to resolve the coating
      structure of tablets. The relative coating thickness over a tablet surface or
      between different tablets of the same batch can be determined with high
      precision. However, in order to determine the absolute coating thickness
      accurately the refractive index, n, of the coating layer needs to be known. For
      all published studies to date the value of n was based on estimates or bulk
      measurements, which were based on the assumption that n is constant for a given
      coating formulation. We have developed a measurement technique using X-ray
      microtomography to independently quantify the coating thickness. These data were
      then used to validate the terahertz imaging results, and we found that the
      intertablet variation of n for coating layers of 25-270 MUm thickness is less
      than 4% and that there is less than 3% intratablet variation in n. Based on our
      results we estimate that, depending on the pigment content, the absolute value of
      n in a typical pharmaceutical coating formulation will be in the range of 1.45 <
      n < 2.01. We conclude that TPI is a robust technique and that, due to its very
      simple measurement principle, it is an ideal measurement technique to quantify
      the coating thickness in process control and quality monitoring applications. 

PMID- 23116337
TI  - Intranasal drug delivery to the central nervous system: present status and future
      outlook.
AB  - Pharmacological treatment of disorders affecting the central nervous system (CNS)
      is a complex task. Different parameters may negatively influence effective
      targeting of the CNS and drug compliance, for example, poor brain-blood barrier
      (BBB) permeability, patient forgetfulness or neglect, and lack of collaboration
      between caregivers and patients. Pharmaceutical science is constantly looking for
      new administration strategies for efficient drug delivery to the CNS that could
      obviate these problems. Drugs can reach the brain through the skin, nasal cavity
      and oral cavity, and while effective transport of drugs from skin and nasal
      cavity to the CNS has been documented, these studies did not stimulate the
      introduction of a substantial number of new drug formulations to treat CNS
      disorders. Nasal drug delivery, generally used to administer locally acting
      molecules, is not common for systemic administration, although the possibility
      and importance of such systemic administration is suggested by several studies.
      This paper reviewed different anatomical and pharmaceutical factors related to
      drug administration through the nasal route, and explored whether nasal delivery
      of selected CNS drugs could improve their pharmacokinetics and patient
      compliance. This route offers attractive advantages, and pharmaceutical
      scientists and anatomists should collaborate to improve CNS drug compliance and
      to increase the number of compounds that can be administered intranasally.

PMID- 23116338
TI  - Antioxidant potential of all-trans retinoic acid (ATRA) and enhanced activity of
      liposome encapsulated ATRA against inflammation and tumor-directed angiogenesis.
AB  - The purpose of this study was to investigate whether all-trans retinoic acid
      (ATRA) has antioxidant property. The study was also focused on its inhibitory
      effect on the acute and chronic inflammation and tumor-associated capillary
      formation in terms of angiogenesis in C57BL/6 mice after incorporated in liposome
      composed of distearoylphosphatidylcholine (DSPC/cholesterol). ATRA possesses a
      number of important biologic activities including oncostatic, antioxidant and
      immunostimulatory actions. Our study was designed to evaluate the antioxidant
      activity of free ATRA by nitric oxide scavenging, superoxide radical scavenging,
      hydroxyl radical scavenging and lipid peroxide scavenging assays. The ATRA showed
      significant scavenging activities in all these antioxidant assays comparable to
      the standard antioxidant. We have also evaluated the activity of encapsulated
      ATRA against anti-inflammatory activity in C57BL/6 mice. The paw oedema
      inhibition was found in carrageenan model as 55.56% and 66.67% for free ATRA and
      encapsulated ATRA treatment respectively and for formaldehyde model it was found
      to be 60.87% and 69.57% respectively compared with saline treated control mice.
      Encapsulated ATRA inhibited the tumor-associated capillary formation in mice
      induced by highly metastatic B16F10 melanoma cells significantly than the free
      ATRA did. In this study the inhibition of tumor-directed capillary formation was
      found to be 56.25% and 62.50% for free ATRA and encapsulated ATRA treatment
      respectively. In conclusion, ATRA showed a significant antioxidant property in
      vitro. Free ATRA has anti-inflammatory activity as proved by us in animal model
      of acute and chronic inflammation and antiangiogenesis activity. Furthermore, its
      activity was boosted by encapsulation in liposome.

PMID- 23116339
TI  - Modeling the closed and open state conformations of the GABA(A) ion channel-
      plausible structural insights for channel gating.
AB  - Recent disclosure of high resolution crystal structures of Gloeobacter violaceus
      (GLIC) in open state and Erwinia chrysanthemii (ELIC) in closed state provides
      newer avenues to advance our knowledge and understanding of the physiologically
      and pharmacologically important ionotropic GABA(A) ion channel. The present
      modeling study envisions understanding the complex molecular transitions involved
      in ionic conductance, which were not evident in earlier disclosed homology
      models. In particular, emphasis was put on understanding the structural basis of
      gating, gating transition from the closed to the open state on an atomic scale.
      Homology modeling of two different physiological states of GABA(A) was carried
      out using their respective templates. The ability of induced fit docking in
      breaking the critical inter residue salt bridge (Glu155beta(2) and Arg207beta(2))
      upon endogenous GABA docking reflects the perceived side chain rearrangements
      that occur at the orthosteric site and consolidate the quality of the model.
      Biophysical calculations like electrostatic mapping, pore radius calculation, ion
      solvation profile, and normal-mode analysis (NMA) were undertaken to address
      pertinent questions like the following: How the change in state of the ion
      channel alters the electrostatic environment across the lumen; How accessible is
      the Cl(-) ion in the open state and closed state; What structural changes
      regulate channel gating. A "Twist to Turn" global motion evinced at the
      quaternary level accompanied by tilting and rotation of the M2 helices along the
      membrane normal rationalizes the structural transition involved in gating. This
      perceived global motion hints toward a conserved gating mechanism among pLGIC. To
      paraphrase, this modeling study proves to be a reliable framework for
      understanding the structure function relationship of the hitherto unresolved
      GABA(A) ion channel. The modeled structures presented herein not only reveal the
      structurally distinct conformational states of the GABA(A) ion channel but also
      explain the biophysical difference between the respective states.

PMID- 23116340
TI  - Shoulder function and active motion deficit in patients with rheumatoid
      arthritis.
AB  - PURPOSE: To discover whether there are differences between patients with RA with
      and without active motion deficit in the shoulder (passive ROM greater than
      active ROM) concerning disease characteristics and shoulder function, and examine
      the role of active motion deficit in explaining limitations of shoulder function
      in daily life. METHODS: This cross-sectional study included 123 patients with RA
      having shoulder pain. Disease activity and duration of shoulder pain and disease
      were registered, active and passive shoulder ROM, pain and muscle strength were
      measured. Shoulder function in daily life was assessed by Disability of the Arm,
      Shoulder and Hand (DASH). RESULTS: Patients with active motion deficit (36%) had
      statistical significant worse scores on disease activity, shoulder pain, muscle
      strength, and DASH function than those without active motion deficit (p <= 0.05).
      No differences between the groups were found for duration of shoulder pain or
      disease (p > 0.05). Active motion deficit, passive ROM, muscle strength and pain
      explained 33.7% of the variation in the DASH function score. CONCLUSION: Active
      motion deficit in the shoulder seems frequent in patients with RA. Together with
      passive ROM, muscle strength and pain, active motion deficit explained about one
      third of the limitations in shoulder function in daily life.

PMID- 23116341
TI  - Remodeling of the folding free energy landscape of staphylococcal nuclease by
      cavity-creating mutations.
AB  - The folding of staphylococcal nuclease (SNase) is known to proceed via a major
      intermediate in which the central OB subdomain is folded and the C-terminal
      helical subdomain is disordered. To identify the structural and energetic
      determinants of this folding free energy landscape, we have examined in detail,
      using high-pressure NMR, the consequences of cavity creating mutations in each of
      the two subdomains of an ultrastable SNase, Delta+PHS. The stabilizing mutations
      of Delta+PHS enhanced the population of the major folding intermediate. Cavity
      creation in two different regions of the Delta+PHS reference protein, despite
      equivalent effects on global stability, had very distinct consequences on the
      complexity of the folding free energy landscape. The L125A substitution in the C
      terminal helix of Delta+PHS slightly suppressed the major intermediate and
      promoted an additional excited state involving disorder in the N-terminus, but
      otherwise decreased landscape heterogeneity with respect to the Delta+PHS
      background protein. The I92A substitution, located in the hydrophobic OB-fold
      core, had a much more profound effect, resulting in a significant increase in the
      number of intermediate states and implicating the entire protein structure.
      Denaturant (GuHCl) had very subtle and specific effects on the landscape,
      suppressing some states and favoring others, depending upon the mutational
      context. These results demonstrate that disrupting interactions in a region of
      the protein with highly cooperative, unfrustrated folding has very profound
      effects on the roughness of the folding landscape, whereas the effects are less
      pronounced for an energetically equivalent substitution in an already frustrated
      region.

PMID- 23116342
TI  - [Extracellular chromosome 21--derived microRNAs in maternal circulation:
      evaluation of their diagnostic potential for screening of Down syndrome].
AB  - OBJECTIVE: Initially, we focused on the detection of extracellular microRNAs in
      maternal circulation, whose genes are located on human chromosome 21 (miR-99a,
      let-7c, miR-125b-2, miR-155 and miR-802). Subsequently, we studied if plasmatic
      concentrations and/or expression profile of extracellular chromosome 21-derived
      microRNAs would distinguish between pregnancies bearing euploid foetuses and
      those affected with Down syndrome. DESIGN: Pilot study. SETTING: Division of
      Molecular Biology and Cell Pathology, Department of Gynaecology and Obstetrics,
      Third Faculty of Medicine, Charles University, Prague. METHODS: 12 women with
      normal course of gestation (mean 16.4 weeks, median 16.0 weeks), 12 pregnancies
      bearing Down syndrome foetus (mean 18.2 weeks, median 18.5 weeks) and 6 non
      pregnant individuals were involved in the retrospective study. RNA enriched for
      small RNAs (including microRNAs) was isolated from 1ml of plasma sample.
      Consequently relevant microRNA was transcribed into cDNA using specific stem-loop
      primer and detected by specific real-time PCR assay. RESULTS: Commercial systems
      enabled reliable detection of 4 out of 5 extracellular chromosome 21-derived
      microRNAs (miR-99a, let-7c, miR-125b-2 and miR-155). Expression profile of
      extracellular miR-99a, miR-125b-2 and miR-155 was significantly higher in the
      cohort of pregnant women than in non-pregnant individuals. Also plasmatic levels
      of miR-99a and miR-125b-2 were significantly increased in pregnant women.
      Unfortunately, the concentrations and gene expression of extracellular chromosome
      21-derived microRNAs (miR-99a, let-7c, miR-125b-2 and miR-155) did not differ
      between the cohorts of pregnancies bearing euploid foetuses and those affected
      with Down syndrome. CONCLUSION: Analysis of extracellular chromosome 21-derived
      microRNAs does not distinguish between pregnancies with euploid and aneuploid
      foetuses and has no benefit for screening programmes.

PMID- 23116343
TI  - [A comparison of different types of suburethral slings in the treatment of
      urinary incontinence in geriatric patients].
AB  - OBJECTIVE: Comparison of different types of tension free tapes in the treatment
      of urinary incontinence in institutionalized elderly patients. DESIGN:
      Prospective randomized study. SETTING: Charles University in Prague, 1st Medical
      Faculty and Hospital Bulovka, Department of Obstetrics and Gynaecology, Prague.
      METHODS: 43 patients of several gerontologic centres with prevailing stress
      urinary incontinence were included based on urinary dysfunction specific
      questionnaire (ICIQ) and cognitive functions objective estimation (MMSE). Three
      types of tapes, TVT-O, MiniArc and Ajust were used and patients were randomized
      into the groups and after an urogynaecologic examination, incl. ultrasound the
      operation was performed. RESULTS: The groups were - except of the age of the
      patients of group MiniArc - well outweighted concerning demographic parameters.
      High success rate of all techniques used evaluated by the QoL questionnaires was
      in all the groups comparable. No case of bleeding, bladder injury or
      postoperative pain was found. Higher frequency of OAB de novo and worsening of
      preexisting symptomatics could be explained by general very high prevalence of
      OAB in the elderly even without the operation. In whole our cohort only 1 case of
      failure to treat and of tape exposure was found. Our results confirming high
      success rate of all the types also in elderly and institutionalized patients are
      in consent with sporadic published data. CONCLUSION: Surgical treatment of cases
      of stress and mixed urinary incontinence is also in cases of elderly polymorbid
      nurcing facilities clients with regard to the high success rate. Secondary
      outcome of our report when accepting the conclusion is drop of the costs of
      antiincontinence pads thus having a significant economic effect.

PMID- 23116344
TI  - [Outcomes of anterior vaginal wall repair using polypropylene mesh].
AB  - INTRODUCTION: Pelvic organ prolapse (POP) is a major health concern especially in
      the elderly women. Anterior vaginal wall prolapse (AWP) represents the most
      common form of POP with reoperation rate 30-40% when primary treated by anterior
      colporrhaphy. Modern surgical techniques of POP repair uses polypropylene (PP)
      mesh implants to better support pelvic structures and lower the risk of
      recurrence. Aim of our study was to assess the safety and efficacy of anterior
      vaginal wall prolapse repair using PP mesh system NAZCA TC (Promedon). The kit
      consists of preformed PP mesh anchored to pelvic structures by two needle
      inserters via pre-pubic and trans-obturator route. METHODS: From January 2010 to
      February 2011, 21 patients with stage III/IV AWP underwent transvaginal repair
      with implantation of PP mesh. The stage of POP measured according to POP-Q
      system, surgery length, blood loss and complications has been evaluated six month
      after the surgery. Surgery has been assessed as successful when POP stage 0/I o
      has been reached. In 42.9% of patients AWP repair was combined with other
      procedures: vaginal hysterectomy or posterior vaginal repair. (Statistical
      evaluation was done by Wilcoxon test.). RESULTS: The average age of operated
      women was 62.4+/-9.4 years, average body mass index was 27.5+/-4.1 kg/m2, with
      overall parity of 2.2+/-1.4 children. The surgery time was 64.0+/-26.0 minutes
      with average blood loss of 185.0+/-17,0 ml. No serious per-operating complication
      has been recorded. The objective cure rate at 6 months was 90.5%. Statistically
      significant difference in the position of points Aa, Ba and C (p<0,05) has been
      observed. Difference in the position of other POP-Q points has not been
      statistically significant. Post operatively one case of small mesh erosion
      managed by observation only has been documented. CONCLUSION: Transvaginal repair
      of AWP with polypropylene mesh is an effective and safe technique in the hands of
      surgeon experienced in classical POP reconstruction techniques. For the
      assessment of long term efficacy the further follow-up of patients is necessary.

PMID- 23116345
TI  - [Intrauterine system (Mirena) and ectopic pregnancy--case report].
AB  - An ectopic pregnancy are most common gynaecological emergencies. The large
      majority (95%) of ectopic pregnancies occur in Fallopian tube. Although pregnancy
      is rare in women who use intrauterine system Mirena, women who do become pregnant
      while using Mirena have a high risk of ectopic pregnancy. These pregnancies can
      be watchful for any signs of an ectopic pregnancy, such a severe abdominal pain
      accompanied by unusual vaginal bleeding.

PMID- 23116346
TI  - [Vascular endothelial growth factor in ovarian cancer patients].
AB  - OBJECTIVE: To compare plasma VEGF (vascular endothelial growth factor) levels in
      ovarian cancer patients, in patients with benign ovarian tumors and healthy
      women. DESIGN: Prospective study. SETTING: Department of Gynecology and
      Obstetrics, Medical Faculty Charles University, Prague and University Hospital,
      Hradec Kralove. Department of Immunology and Alergology, Medical Faculty Charles
      University, Prague and University Hospital, Hradec Kralove. METHODS: VEGF was
      estimated by ELISA (R&D Systems). RESULTS: We found that plasma VEGF levels were
      associated with the International Federation of Gynecology and Obstetrics (FIGO)
      stage (FIGO I+II, n=8) Med = 425,53 pg/ml (range 142,30-982,40 pg/ml), (FIGO
      III+IV, n=29) Med = 941,48 pg/ml (range202,10-2857,80 pg/ml) (p=0,03). Patients
      with primary ovarian cancer (n=37) had a significantly higher plasma VEGF level
      Med = 829,93 pg/ml (range142,30-2857,80 pg/ml), compared with patients with
      benign ovarian tumors (n=15) Med = 426,28 pg/ml (range 32,00-922,20 pg/ml) and
      healthy women (n=21) Med = 283,13 pg/ml (range 80,50-735,20 pg/ml) (p=0,0003).
      VEGF levels were lower in plasma (n=79) Med = 575,49 pg/ml (range 55,80-2185,00
      pg/ml) compared with VEGF levels in ascitic fluid (n=37) Med = 745,74 pg/ml
      (range 142,30-2185,00 pg/ml) (p=0,04) in ovarian cancer patients. CONCLUSION:
      Plasma VEGF assay before primary treatment and the changes during the other
      treatment should contribute to better understanding of angiogenesis in ovarian
      cancer patients. Plasma VEGF correlates with the stage of primary ovarian cancer.

PMID- 23116347
TI  - [Gitelman syndrome in pregnancy--a severe hypokalemia with favorable perinatal
      prognosis].
AB  - Gitelman syndrom is a rare congenital tubulopathy characterized by hypokalemia,
      hypomagnesemia, metabolic alkalosis and hypocalciuria. We report a case of a 32
      year-old patient admitted for asymptomatic hypokalemia and hypomagnesemia in the
      30th week of gestation. A diagnosis of Gitelman syndrom was made and intravenous
      administration of potassium chloride in high doses combined with spironolactone
      was started. Despite intensive potassium supplementation (8 g/day), the serum
      potassium levels remained at the lower limit of normality throughout the
      pregnancy. The patient delivered a healthy female 2670 g/48 cm after labor
      induction in the 39th week of gestation. A summary of 22 so far published cases
      of Gitelman syndrome in pregnancy is presented. The analysis of published case
      studies suggests a need for ion supplementation, reduction of urinary potassium
      wasting, monitoring of fetal well-being and amniotic fluid levels. Pregnancy has
      a very favorable perinatal prognosis despite critical serum levels of potassium
      and magnesium throughout the pregnancy.

PMID- 23116348
TI  - [Course of congenital malformation incidences and their changes over time in
      children born in the Czech Republic].
AB  - AIM OF STUDY: An analysis of incidences of selected birth defects in the Czech
      Republic in 2000 - 2008 period. TYPE OF STUDY: Retrospective epidemiological
      analysis of birth defects incidences in births and total birth defects incidences
      (including prenatally diagnosed cases) from the Czech National Birth Defects
      Register database. MATERIAL AND METHODS: Data from the National Birth Defects
      Register (Institute for Health Information and Statistics) in the Czech Republic
      in the 2000 - 2008 period were used along with data on prenatally diagnosed
      defects from particular departments of medical genetics. Sixteen selected defects
      (anencephaly, spina bifida, encephalocele, congenital hydrocephalus, coarctation
      of aorta, transposition of great vessels, hypoplastic left heart syndrome, Fallot
      tetralogy, omphalocele, gastroschisis, diaphragmatic hernia, oesophageal atresia
      and stenosis, anorectal malformations, Down syndrome, Edwards syndrome and Patau
      syndrome) were analyzed in detail. RESULTS: There were 119 570 live births (61
      326 boys and 58 244 girls) in 2008. In the same period, 4664 live births with a
      birth defect (under the age of one year) were reported, out of which 2754 boys
      and 1910 girls. Mean incidence was 390.06 (449.08 in boys and 327.93 in girls)
      per 10 000 live births. In 1994 - 2006, totally 1 238 398 children were born, out
      of which more than 42 000 with a birth defect. In the 2000 - 2006 period,
      absolute numbers of diagnosed live births with birth defect varied between 3600 -
      3800 cases per year while in 2007 and 2008 years absolute numbers raised over
      4600 cases per year. During 2000 - 2008 period following mean incidences (per 10
      000 live births) of selected defects were ascertained (total incidences including
      prenatal diagnostics in brackets): anencephaly 0 - 0.3 (1.9 - 3.7), spina bifida
      0.7 - 2.3 (3.2 - 5.2), encephalocele 0.1 - 0.4 (0.9 - 2.4), congenital
      hydrocephalus 1.6 - 3.5 (5.3 - 7.0), coarctation of aorta 3.9 - 5.2 (4.8 - 6.1),
      transposition of great vessels 2.9 - 4.5 (3.2 - 5.0), hypoplastic left heart
      syndrome 0.7 - 2.3 (2.2 - 4.3), Fallot tetralogy 2.6 - 4.0 (3.2 - 4.4),
      omphalocele 1.0 - 1.7 (1.8 - 3.8), gastroschisis 0.2 - 1.2 (2.4 - 3.4),
      diaphragmatic hernia 1.3 - 2.9 (1.5 - 3.9), Down syndrome 3.3 - 6.5 (15.8 -
      22.2), Edwards syndrome 0.2 - 1.0 (3.5 - 5.8) and Patau syndrome 0.2 - 1.0 (1.2 -
      2.6). CONCLUSIONS: There has been no major change in birth defect incidences in
      live births in the Czech Republic in last years. Number of non-viable defects has
      decreased in stillbirths and in perinatal mortality in the Czech Republic. An
      incidence of some defects has decreased mostly due to a nation-wide system of
      prenatal diagnostics; some incidences remain stable in live-birth population in
      others incidences have increased. A total incidence has mostly increased
      (anencephaly being an exception) mostly due to an earlier prenatal diagnostics.
      In chromosomal syndromes, an increasing maternal age as well as a growing number
      of mothers of 35 years of age and over has contributed to the increased
      incidences.

PMID- 23116349
TI  - [Prenatal diagnostics of birth defects in the Czech Republic--a fifteen-year
      period].
AB  - AIM OF STUDY: An analysis of prenatal and postnatal incidences of selected birth
      defects and secondary prevention efficiency in the Czech Republic in 1994 - 2008
      period. TYPE OF STUDY: Retrospective epidemiological analysis of birth defects
      data from particular centers of clinical genetics and prenatal diagnostics
      (prenatal data) and from the Czech National Birth Defects Register database
      (birth data). MATERIAL AND METHODS: Data from the National Birth Defects Register
      (Institute for Health Information and Statistics of the Czech Republic) were used
      along with data from particular centers of clinical genetics and prenatal
      diagnostics covering the whole area of the Czech and the 1994 - 2008 period.
      Total prenatal diagnostics efficiency and an efficiency of prenatal diagnostics
      of 5 selected defects (anencephaly, spina bifida, omphalocele, gastroschisis and
      Down syndrome) were studied. RESULTS: In the period under study the number of
      prenatally diagnosed birth defects has increased. In 1994, the incidence of
      prenatally diagnosed (and selectively terminated) birth defects was 27.40 per 10
      000 live births while in 2008 it was 73.26 per 10 000. In prenatally diagnosed
      but not terminated defects the corresponding numbers were 8.91 in 1994 and 32.87
      in 2008. In last years, a quality change in prenatal birth defects screening has
      taken place in the Czech Republic. A first trimester screening with an increased
      efficiency not only for Down syndrome (DS) has been used more often implicating a
      wider application of chorionic villi sampling (CVS). An increased screening
      efficiency also made possible a relative decrease of invasive prenatal
      diagnostics procedures necessary to diagnose a single case of Down syndrome. When
      comparing CVS and amniocentesis from this particular point of view a higher CVS
      efficiency (about 12 CVS versus some 120 amniocenteses per 1 case of DS).
      Prenatal diagnostics efficiency has increased in all defects under study over the
      1994 - 2008 period, being about 80% in DS almost 10% in anencephaly, 65 - 68% in
      omphalocele and gastroschisis and 80% in spina bifida in last years. CONCLUSIONS:
      Chromosomal aberration (DS especially) are among the most frequent prenatally
      diagnosed birth defects, further being heart defects, neural tube defects
      (anencephaly, encephalocele, spina bifida), hydrocephalus, congenital skeletal
      system defects, abdominal wall defects (omphalocele, gastroschisis) and renal
      defects. In some defects, prenatal diagnostics has also significantly influenced
      their incidence in births (anencephaly, gastroschisis and DS e.g.).

PMID- 23116350
TI  - [HE4 a biomarker of ovarian cancer].
AB  - OBJECTIVE: Verification of the importance of determination of HE4 and calculation
      of ROMA index for increasing the efficiency of diagnosis of ovarian cancer in a
      population of Czech women. DESIGN: Prospective study. SETTING: Department of
      Gynaecology and Obstetrics, Faculty Hospital in Pilsen. METHODS: In the period
      from 06/24/2010 to 12/01/2011 was at the Department of Gynaecology and
      Obstetrics, University Hospital Pilsen examined 552 patients with abnormalities
      in the pelvis. Patients were divided into two groups. There were 30 women with
      histologically confirmed malignant ovarian tumors. Another 522 women had benign
      findings. According to the levels of FSH were women in both groups divided into
      premenopausal and postmenopausal. At all women were measured CA 125, HE4 and FSH.
      HE4 and CA125 were determined using the chemiluminescent device Architect 1000
      (Abbott, USA), FSH chemiluminescent method on the device DXI 800 (Beckman
      Coulter, USA). At all premenopausal women was calculated ROMA1 index and at all
      postmenopausal women ROMA2 index. SAS statistical software 9.2 were used for all
      statistical calculations. RESULTS: The highest diagnostic efficiency was achieved
      by a combination of HE4 and CA125 markers with the calculation ROMA2 index for
      postmenopausal women. In determining of menopausal status according to the values
      of FSH cut-off for menopause 40 IU/L and cut-off at 26.4% for ROMA2 reaches ROMA2
      sensitivity of 92.3%, specificity of 88.5% and PV- of 99.3%. If we reduce the cut
      off for laboratory diagnosis of menopause using FSH at 22 IU/L, and cut-off for
      ROMA2 was 26.3% reaches ROMA2 sensitivity of 95.2%, specificity of 87.8% and PV-
      of 99.5%. CONCLUSION: HE4 in combination with CA125 and current ROMA index
      calculation is a suitable methodology to improve the detection of ovarian cancer.

PMID- 23116351
TI  - [Obesity and male infertility].
AB  - The authors present a review on the effects of obesity on male fertility. Current
      scientific findings suggest an elevated risk of infertility among couples in
      which the male partner is obese. In obese men can be found reduced serum levels
      of androgens and SHBG and increased estrogen levels without compensatory increase
      in FSH. Among other impacts of male obesity that may contribute to increased risk
      of infertility are altered retention and metabolism of environmental toxins,
      lifestyle, sexual dysfunction, genetic factors, excessive secretion of hormones
      derived from adipose tissue, oxidative stress, sperm specific proteomic changes
      or elevated levels of cytokines. The increasing prevalence of obesity calls for
      greater clinical awareness of its impact on male fertility.

PMID- 23116352
TI  - [Pregnant women and mothers using alcohol, tobacco and illegal drugs].
AB  - This analysis is focused on use of addictive substances among women hospitalised
      during delivery or puerperium. Analysed data come from National Registry of
      Mothers at Childbirth and from National Registry of Newborns, which are managed
      by the Institute of Health Information and Statistics. GOAL: To describe the
      prevalence of addictive substances use among women during gestation and to study
      its relation to health complications during pregnancy, delivery or puerperium and
      to health status of foetus and newborns. METHODS AND MATERIALS: The reporting to
      registries is provided in the Report on mother at childbirth and in the Report on
      newborn. Both registers provide basic socio-demographic information about mother,
      information about previous pregnancies and abortions, about current pregnancy,
      course of delivery, birth and neonatal treatment and health of newborn during
      hospitalization of mother during delivery or puerperium. Use of addictive
      substances is monitored in the National Registry of Mothers at Childbirth since
      2000. Addictive substances are divided to tobacco, alcohol and drugs. Descriptive
      analysis of data was performed and binary logistic regression was used to test
      association of substance use with education and marital status (adjusted for
      age), analysis of variance was used to test association of substance use with
      selected health complications of pregnancy, delivery or puerperium and with
      health status of foetus/newborns (adjusted for age, education, marital status and
      interaction between addictive substances). RESULTS: In 2000-2009, 1,008,821
      mothers were reported of whom 60,502 women were registered as cigarette smokers,
      1,528 used alcohol and 1,836 used other (illegal) drugs. Total of 1,027,200
      newborns were reported. The average age of mothers using addictive substances
      were about 0.5-3 years lower in comparison with nonusers, in average mothers
      using illegal drugs were the youngest. Mothers using addictive substances were
      more often unmarried and had lower education than nonusers - almost 2/3 of
      mothers using addictive substances were unmarried or didn't live in permanent
      partnership and more than 82% of mothers-users have lower education (primary or
      secondary school without a diploma). The association between substance use and
      induced and spontaneous abortions was observed only in smokers. Serious
      complications of pregnancy were associated with all monitored addictive
      substances - in mothers-smokers, a probability of serious complications were
      about 40 %, in users of illicit drugs about 13 % and in alcohol users about 5 %
      higher as compared to nonusers. Substance use showed almost no association with
      problems during childbirth. Alcohol and illegal drugs use increased probability
      of complications in puerperium. Health status of foetus/newborn was negatively
      significantly altered mainly in those born to mothers-smokers in almost all
      observed characteristics. Mothers alcohol use during pregnancy was associated
      primarily with the overall health status of foetus immediately after delivery,
      congenital anomalies, stillbirth or need for treatment of newborn in the theatre.
      Infants of mothers using addictive substances had higher probability of
      consequent hospitalization after discharge from the neonatal department, transfer
      to infant home and death of infant. CONCLUSION: Association between complications
      during pregnancy, delivery and puerperium and health status of newborns and
      substance use of mothers during pregnancy was found mainly in cigarette smoking.
      Alcohol use was found significant in some (but serious) health problems of
      mothers and newborns. The association between illegal drugs and monitored
      indicators wasn't found. Following the results of this work, criteria for
      reporting of illegal drug use in mothers during pregnancy should be improved.

PMID- 23116353
TI  - [A new opportunity in ovarian cancer treatment].
AB  - OBJECTIVE: Targeted treatment in ovarian cancer patients. DESIGN: Practical
      paper. SETTING: Department of Gynecology and Obstetrics, Medical Faculty Charles
      University, Prague and University Hospital, Hradec Kralove. CONCLUSION: Targeted
      treatment is possible based on particular characteristics of single tumors in
      ovarian cancer patients. Better understanding of tumor biology should contribute
      to predict certain patients would benefit most from use of targeted treatment.

PMID- 23116354
TI  - [Comparison of prolactin, free T3 and free T4 levels in the follicular fluid of
      infertile women and healthy fertile oocyte donors].
AB  - OBJECTIVE: Follicular fluid (FF) provides an important microenvironment for the
      development of oocytes. The biochemical composition of the FF plays critical role
      in the oocyte competence. The aim of our study was to compare the levels of
      selected hormones in FF of infertile women and healthy fertile oocyte donors.
      DESIGN: Retrospective comparative study. SETTING: Department of Histology and
      Embryology, Faculty of Medicine in Pilsen, Charles University in Prague;
      Department of Gynecology and Obstetrics, Charles University and University
      Hospital in Pilsen; Institute of Reproductive Medicine and Endocrinology, IVF
      Centers Prof. Zech, Plzen. METHODS: Levels of prolactin, free T3 and free T4
      hormones in the FF of 146 women were analyzed. We have analysed FF of 74
      infertile patients (mean age 31 years, SD = 4.65) and 72 healthy fertile oocyte
      donors (mean age 26 years, SD = 4.44). Only blood free samples were studied after
      pooling of all FF samples each patient. Levels of hormones were determined using
      ECLIA method (Electro-Chemi-Luminiscent Immunoassay) on the Cobas e411. RESULTS:
      RESULTS showed statistically significantly higher levels of prolactin (p=0.0006)
      and free T4 hormone (p=0.0246) in FF of infertile women in comparison to the
      group of healthy fertile oocyte donors. CONCLUSION: Our study confirms the
      presence of prolactin and thyroid hormones in FF and it can be suggested that
      they play a key role in the regulation of reproductive processes. The study of FF
      from donors and their detailed comparison with infertile patients with various
      gynaecological causes of infertility has great value for better understanding of
      regulatory mechanisms of fertility.

PMID- 23116355
TI  - [Prevalence of Chlamydia trachomatis infection in patients treated for
      infertility].
AB  - AIM OF THE STUDY: To determine the prevalence of Chlamydia trachomatis infection
      in patients treated for infertility. STUDY TYPE: A retrospective analysis.
      SETTING: Fertimed, infertility treatment center, Olomouc. METHOD: At Fertimed, we
      used DNA detection of Chlamydia trachomatis by the PCR method of the company
      GeneProof to examine, between 2009-2011, 785 women undergoing one of the
      infertility treatment methods and their 113 partners. In the second group, we
      examined 121 oocyte donors and 30 men before sperm donation. We appraised the
      frequency of Chlamydia trachomatis detection in the specific groups and the
      clinical impact of the infection on the female reproductive organs. RESULTS: In
      the group of women treated for infertility, we detected 20 (2.5%) women with an
      active infection. After treatment, 9 of them underwent an examination of
      Fallopian tube patency using the UTHL (ultrasonographically guided transvaginal
      hydrolaparoscopy) method. In 7 cases, we indicated a bilateral salpingectomy due
      to a sactosalpinx and in one case severe pelvic adhesions were found (88.9%), and
      in one patient, the result was normal. In the control group of 43 PCR-negative
      women who were examined for Fallopian tube patency, 9.3% rate of tubal pathology
      was found (p<0.001). In the oocyte donor group, we detected the presence of
      Chlamydia trachomatis in 12 (9.9%) women, and in the sperm donor group, in 7.6%
      men. Treatment with 500 mg of Sumamed (azithromycin), given in 3 doses, was
      successful in all of the positive patients. CONCLUSION: We found that Chlamydia
      trachomatis detection was lower in the women treated for infertility than in the
      female donor group. Women with a confirmed infection had a high prevalence of
      inflammatory changes in the Fallopian tubes compared with women devoid of a
      confirmed infection. The treatment with azithromycin is effective.

PMID- 23116357
TI  - Differential effects of LPS from Escherichia coli and Porphyromonas gingivalis on
      IL-6 production in human periodontal ligament cells.
AB  - OBJECTIVE: Periodontal ligament (PDL) cells produce IL-6 upon stimulation with
      inflammation promoters, but the signaling pathways involved have not been
      characterized. This study investigates underlying mechanisms behind regulation of
      PDL cell IL-6 production by E. coli and P. gingivalis LPS. MATERIALS AND METHODS:
      Human PDL cells, endothelial cells and monocytes were stimulated with E. coli or
      P. gingivalis LPS in the presence or absence of pharmacological agents in order
      to disclose pathways involved in LPS signaling. Gene expression and cellular
      protein levels were assessed by quantitative real-time PCR and ELISA,
      respectively. RESULTS: Stimulation with LPS from E. coli (1 ug/ml) for 24 h
      enhanced PDL cell IL-6 expression several fold, demonstrated both on transcript
      and protein levels, but P. gingivalis LPS (1-5 ug/ml) had no effect. TLR2 mRNA
      was more highly expressed than TLR4 transcript in PDL cells. Treatment with the
      non-selective nitric oxide synthase inhibitor L-NAME (100 uM) reduced E. coli LPS
      induced PDL cell IL-6 by 30%, while neither aminoguanidine (10 uM), an inhibitor
      of inducible nitric oxide synthase, nor estrogen (17beta-estradiol, 100 nM)
      influenced IL-6. Treatment with the glucocorticoid dexamethasone (1 uM) totally
      prevented the E. coli LPS-induced PDL cell IL-6. In endothelial cells, neither E.
      coli LPS nor P. gingivalis LPS promoted IL-6 production. In monocytes, serving as
      positive control, both E. coli and P. gingivalis LPS stimulated IL-6.
      CONCLUSIONS: E. coli LPS but not P. gingivalis LPS stimulates PDL cell IL-6
      production through a glucocorticoid-sensitive mechanism involving nitric oxide
      formation, probably via endothelial nitric oxide synthase.

PMID- 23116356
TI  - Protective effects of rutin against potassium bromate induced nephrotoxicity in
      rats.
AB  - BACKGROUND: Rutin, a polyphenolic flavonoid, was investigated for its protective
      effects against the KBrO(3) induced renal injuries in rat. METHODS: Group I was
      control (untreated), group II was given saline 0.5 ml/kg bw (0.9% NaCl), group
      III was administered KBrO(3) (20 mg/kg bw) intragastric twice a week for four
      weeks. Rutin was administered to group VI (50 mg/kg bw) and Group V (70 mg/kg bw)
      along with KBrO(3) (20 mg/kg bw) while group VI was given rutin (70 mg/kg bw)
      alone twice a week for four weeks. Protective effects of rutin on KBrO(3)-induced
      nephrotoxicity in rats were determined for biochemical parameter of urine, and
      serum, various antioxidant enzymes, DNA and histopathological damages in kidneys.
      RESULTS: The level of urinary red blood cells, leucocytes count, specific
      gravity, urea, creatinine and urobilinogen was increased (P<0.01) whereas
      creatinine clearance was reduced. Serum level of protein, albumin, globulin,
      nitrite, creatinine and blood urea nitrogen (BUN) was significantly increased
      (P<0.01) by KBrO(3). Marked histopathological lesions, elevated DNA fragmentation
      and AgNORs count in renal tissues was determined. Activity of antioxidant
      enzymes; catalase, superoxide dismutase, glutathione peroxidase, glutathione-S
      transferase, glutathione reductase, and reduced glutathione contents were
      decreased (P<0.01) while thiobarbituric acid reactive substances were increased
      (P<0.01) with KBrO(3) treatment in kidneys. DNA ladder assay was intimately
      related with the DNA fragmentation assay. Telomerase activity was found positive
      in the KBrO(3) treated kidneys. Treatment with rutin effectively ameliorated the
      alterations in the studied parameters of rat. Rutin administration alone to rats
      did not exhibit any significant change in any of the parameters studied.
      CONCLUSION: These results suggest that rutin works as an antioxidant in vivo by
      scavenging reactive oxygen species and this serves to prevent oxidative renal
      damage in rat treated with KBrO(3).

PMID- 23116358
TI  - Diagnostic value of JAK2 V617F somatic mutation for myeloproliferative cancer in
      49 488 individuals from the general population.
AB  - The JAK2 V617F somatic mutation is present in the majority of patients with
      myeloproliferative cancer (polycythaemia vera, essential thrombocytosis, and
      primary myelofibrosis). However, the diagnostic value of the JAK2 V617F somatic
      mutation for myeloproliferative cancer in the general population is unknown. We
      examined this question in 49 488 individuals from the Copenhagen General
      Population Study. We also examined the association between JAK2 V617F somatic
      mutation, rs10974944 germline genotype, haematological phenotype, any cancer,
      haematological cancer, myeloproliferative cancer, ischaemic heart disease, and
      venous thromboembolism. The JAK2 V617F somatic mutation was present in 0.1% (n =
      68), increasing across rs10974944 germline genotypes (P-trend = 0.001). JAK2
      V617F somatic mutation positives versus negatives had higher erythrocyte (P = 2 *
      10(-5) ), thrombocyte (P = 2 * 10(-16) ), and leucocyte (P = 4 * 10(-9) ) counts,
      and had 2.7-/2.5-fold risk of cancer (prevalent/incident), 44-/28-fold risk of
      haematological cancer, 221-/97-fold risk of myeloproliferative cancer, 2.2-/1.2
      fold risk of ischaemic heart disease, and 3.1-/1.0-fold risk of venous
      thromboembolism. By combining conventional haematological parameters with a test
      for the JAK2 V617F somatic mutation, myelo;?>proliferative cancer could be
      identified or ruled out with a sensitivity of 47-100% and a specificity of 98
      100%. In conclusion, in the general population the JAK2 V617F somatic mutation
      has a high diagnostic value for myeloproliferative cancer when combined with
      conventional haematological parameters.

PMID- 23116359
TI  - Tailored nanoporous coatings fabricated on conformable polymer substrates.
AB  - Nanoporous coatings have become the subject of intense investigation, in part
      because they have been shown to have unique and tailorable physical properties
      that can depart greatly from their dense or macroscopic counterparts. Nanoporous
      coatings are frequently fabricated utilizing oblique-angle or glancing-angle
      physical vapor-phase deposition techniques. However, a significant limitation for
      such coatings exists; they are almost always deposited on smooth and rigid planar
      substrates, such as silicon and glass. This limitation greatly constrains the
      applicability, tailorability, functionality and even the economic viability, of
      such nanoporous coatings. Here, we report our findings on nanoporous/polymer
      composite systems (NPCS) fabricated by utilizing oblique-angle electron-beam
      methodology. These unique composite systems exhibit several favorable
      characteristics, namely, (i) fine-tuned control over coating nanoporosity and
      thickness, (ii) excellent adhesion between the nanoporous coating and polymer
      substrate, (iii) the ability to withstand significant and repeated bending, and
      (iv) the ability to be molded conformably on two and three-dimensional surfaces
      while closely retaining the composite system's designed nanoporous film structure
      and, hence, properties.

PMID- 23116360
TI  - Systems analysis of primary Sjogren's syndrome pathogenesis in salivary glands
      identifies shared pathways in human and a mouse model.
AB  - INTRODUCTION: Primary Sjogren's syndrome (pSS) is a chronic autoimmune disease
      with complex etiopathogenesis. Despite extensive studies to understand the
      disease process utilizing human and mouse models, the intersection between these
      species remains elusive. To address this gap, we utilized a novel systems biology
      approach to identify disease-related gene modules and signaling pathways that
      overlap between humans and mice. METHODS: Parotid gland tissues were harvested
      from 24 pSS and 16 non-pSS sicca patients and 25 controls. For mouse studies,
      salivary glands were harvested from C57BL/6.NOD-Aec1Aec2 mice at various times
      during development of pSS-like disease. RNA was analyzed with Affymetrix HG
      U133+2.0 arrays for human samples and with MOE430+2.0 arrays for mouse samples.
      The images were processed with Affymetrix software. Weighted-gene co-expression
      network analysis was used to identify disease-related and functional pathways.
      RESULTS: Nineteen co-expression modules were identified in human parotid tissue,
      of which four were significantly upregulated and three were downregulated in pSS
      patients compared with non-pSS sicca patients and controls. Notably, one of the
      human disease-related modules was highly preserved in the mouse model, and was
      enriched with genes involved in immune and inflammatory responses. Further
      comparison between these two species led to the identification of genes
      associated with leukocyte recruitment and germinal center formation. CONCLUSION:
      Our systems biology analysis of genome-wide expression data from salivary gland
      tissue of pSS patients and from a pSS mouse model identified common dysregulated
      biological pathways and molecular targets underlying critical molecular
      alterations in pSS pathogenesis.

PMID- 23116361
TI  - The Prostate Cancer Registry: monitoring patterns and quality of care for men
      diagnosed with prostate cancer.
AB  - OBJECTIVE: To establish a pilot population-based clinical registry with the aim
      of monitoring the quality of care provided to men diagnosed with prostate cancer.
      PATIENTS AND METHODS: All men aged >18 years from the contributing hospitals in
      Victoria, Australia, who have a diagnosis of prostate cancer confirmed by
      histopathology report notified to the Victorian Cancer Registry are eligible for
      inclusion in the Prostate Cancer Registry (PCR). A literature review was
      undertaken aiming to identify existing quality indicators and source evidence
      based guidelines from both Australia and internationally. RESULTS: A Steering
      Committee was established to determine the minimum dataset, select quality
      indicators to be reported back to clinicians, identify the most effective
      recruitment strategy, and provide a governance structure for data requests;
      collection, analysis and reporting of data; and managing outliers. A minimum
      dataset comprising 72 data items is collected by the PCR, enabling ten quality
      indicators to be collected and reported. Outcome measures are risk adjusted
      according to the established National Comprehensive Cancer Network and Cancer of
      the Prostate Risk Assessment Score (surgery only) risk stratification model.
      Recruitment to the PCR occurs concurrently with mandatory notification to the
      state-based Cancer Registry. The PCR adopts an opt-out consent process to
      maximize recruitment. The data collection approach is standardized, using a
      hybrid of data linkage and manual collection, and data collection forms are
      electronically scanned into the PCR. A data access policy and escalation policy
      for mortality outliers has been developed. CONCLUSIONS: The PCR provides
      potential for high-quality population-based data to be collected and managed
      within a clinician-led governance framework. This approach satisfies the
      requirement for health services to establish quality assessment, at the same time
      as providing clinically credible data to clinicians to drive practice
      improvement.

PMID- 23116362
TI  - The role of genetic structure in the adaptive divergence of populations
      experiencing saltwater intrusion due to relative sea-level rise.
AB  - Saltwater intrusion into estuaries creates stressful conditions for nektonic
      species. Previous studies have shown that Gambusia affinis populations with
      exposure to saline environments develop genetic adaptations for increased
      survival during salinity stress. Here, we evaluate the genetic structure of G.
      affinis populations, previously shown to have adaptations for increased salinity
      tolerance, and determine the impact of selection and gene flow on structure of
      these populations. We found that gene flow was higher between populations
      experiencing different salinity regimes within an estuary than between similar
      marsh types in different estuaries, suggesting the development of saline-tolerant
      phenotypes due to local adaptation. There was limited evidence of genetic
      structure along a salinity gradient, and only some of the genetic variation among
      sites was correlated with salinity. Our results suggest limited structure,
      combined with selection to saltwater intrusion, results in phenotypic divergence
      in spite of a lack of physical barriers to gene flow.

PMID- 23116364
TI  - The therapist's attachment representation and the patient's attachment to the
      therapist.
AB  - This study examines the relationship between the therapist's own attachment
      representation (Adult Attachment Interview, AAI) and the patient's attachment
      relationship to the therapist (client's attachment to the therapist, CATS). The
      attachment representations of n=22 psychotherapists who treated n=429 patients
      were assessed. A general effect of the secure/insecure therapist attachment
      status on the attachment of the patient to the therapist was not found whereas
      the more specific effects expected could be confirmed: The more preoccupied the
      therapist's attachment status was, the more the patient experienced a preoccupied
      merger attachment to the therapist. The more dismissing the therapist's
      attachment status was, the more the patient experienced an avoidant-fearful
      attachment to the therapist. In summary, not the general security/insecurity of
      the therapist's attachment representation but rather the type of the insecurity
      is associated with the subjective patient's attachment-related experience of the
      therapeutic dyad.

PMID- 23116365
TI  - Direct lipid profiling of single cells from inkjet printed microarrays.
AB  - The on-demand printing of living cells using inkjet technologies has recently
      been demonstrated and allows for the controlled deposition of cells in
      microarrays. Here, we show that such arrays can be interrogated directly by robot
      controlled liquid microextraction coupled with chip-based nanoelectospray mass
      spectrometry. Such automated analyses generate a profile of abundant membrane
      lipids that are characteristic of cell type. Significantly, the spatial control
      in both deposition and extraction steps combined with the sensitivity of the mass
      spectrometric detection allows for robust molecular profiling of individual
      cells.

PMID- 23116363
TI  - Early stage development of the glycine-1 re-uptake inhibitor SCH 900435: central
      nervous system effects compared with placebo in healthy men.
AB  - AIMS: To report the first three studies with SCH 900435, a selective glycine-1 re
      uptake inhibitor in development for treating schizophrenia, using systematic
      evaluations of pharmacodynamics to understand the observed effects. METHODS:
      Three double-blind, placebo-controlled studies (single, visual effect and
      multiple dose) were performed. In the single and multiple dose study SCH 900435
      (0.5-30 mg) was given to healthy males and frequent pharmacokinetic and
      pharmacodynamic measurements were performed. The visual effects study
      incorporated visual electrophysiological measures of macular, retinal and
      intracranial visual pathway function. RESULTS: In the single dose study (highest
      difference, 95% CI, P) increases in smooth pursuit eye movements (8, 12 mg (
      6.09, 10.14, -2.04, 0.013), 30 mg), pupil : iris ratio (20 and 30 mg (-0.065,
      0.09, -0.04, <0.0001)), VAS colour perception (30 mg (-9.48, 13.05, -5.91,
      <0.0001)) and changes in spontaneous reports of visual disturbance were found,
      while FSH (8 mg (0.42, 0.18, 0.66, 0.0015), 12, 20 mg), LH (8-30 mg (1.35, 0.65,
      2.05, 0.0003)) and EEG alpha2 activity decreased (12, 20, 30 mg (0.27, 0.14,
      0.41, 0.0002)). A subsequent dedicated visual effects study demonstrated that
      visual effects were transient without underlying electrophysiological changes.
      This provided enough safety information for starting a multiple ascending dose
      study, showing less visual symptoms after twice daily dosing and titration,
      possibly due to tolerance. CONCLUSIONS: Several central nervous system (CNS)
      effects and gonadotropic changes resulted from administration of 8 mg and higher,
      providing evidence for CNS penetration and pharmacological activity of SCH
      900435. Antipsychotic activity in patients, specificity of the reported effects
      for this drug class and possible tolerance to visual symptoms remain to be
      established.

PMID- 23116366
TI  - Tandem hydroformylation/hydrogenation of alkenes to normal alcohols using Rh/Ru
      dual catalyst or Ru single component catalyst.
AB  - The catalyst system for tandem hydroformylation/hydrogenation of terminal alkenes
      to the corresponding homologated normal alcohol was developed. The reaction
      mechanism for the Rh/Ru dual catalyst was investigated by real-time IR monitoring
      experiments and (31)P NMR spectroscopy, which proved the mutual orthogonality of
      Rh-catalyzed hydroformylation and Ru-catalyzed hydrogenation. Detailed
      investigation about Ru-catalyzed hydrogenation of undecanal under H(2)/CO
      pressure clarified different kinetics from the hydrogenation under H(2) and gave
      a clue to design more active hydrogenation catalysts under H(2)/CO atmosphere.
      The solely Ru-catalyzed normal selective hydroformylation/hydrogenation is also
      reported.

PMID- 23116367
TI  - Heart failure among Indigenous Australians: a systematic review.
AB  - BACKGROUND: Cardiovascular diseases contribute substantially to the poor health
      and reduced life expectancy of Indigenous Australians. Heart failure is a common,
      disabling, progressive and costly complication of these disorders. The
      epidemiology of heart failure and the adequacy of relevant health service
      provision in Indigenous Australians are not well delineated. METHODS: A
      systematic search of the electronic databases PubMed, Embase, Web of Science,
      Cinahl Plus, Informit and Google Scholar was undertaken in April 2012 for peer
      reviewed journal articles relevant to the topic of heart failure in Indigenous
      Australians. Additionally, a website search was done to identify other pertinent
      publications, particularly government reports. RESULTS: There was a paucity of
      relevant peer-reviewed research, and government reports dominated the results.
      Ten journal articles, 1 published conference abstract and 10 reports were
      eligible for inclusion. Indigenous Australians reportedly have higher morbidity
      and mortality from heart failure than their non-Indigenous counterparts (age
      standardised prevalence ratio 1.7; age-standardised hospital separation ratio
      >=3; crude per capita hospital expenditure ratio 1.58; age-adjusted mortality
      ratio >2). Despite the evident disproportionate burden of heart failure in
      Indigenous Australians, the accuracy of estimation from administrative data is
      limited by poor indigenous identification, inadequate case ascertainment and
      exclusion of younger subjects from mortality statistics. A recent journal article
      specifically documented a high prevalence of heart failure in Central Australian
      Aboriginal adults (5.3%), noting frequent undiagnosed disease. One study examined
      barriers to health service provision for Indigenous Australians in the context of
      heart failure. CONCLUSIONS: Despite the shortcomings of available published data,
      it is clear that Indigenous Australians have an excess burden of heart failure.
      Emerging data suggest that undiagnosed cases may be common in this population. In
      order to optimise management and to inform policy, high quality research on heart
      failure in Indigenous Australians is required to delineate accurate
      epidemiological indicators and to appraise health service provision.

PMID- 23116368
TI  - Identifying patients suitable for palliative care--a descriptive analysis of
      enquiries using a Case Management Process Model approach.
AB  - BACKGROUND: In Germany, case management in a palliative care unit was first
      implemented in 2005 at the Department of Palliative Medicine at the University
      Hospital Cologne. One of the purposes of this case management is to deal with
      enquiries from patients and their relatives as well as medical professionals.
      Using the Case Management Process Model of the Case Management Society of America
      as a reference, this study analysed (a) how this case management was used by
      different enquiring groups and (b) how patients were identified for case
      management and for palliative care services. The first thousand enquiries were
      analysed considering patient variables, properties of the enquiring persons and
      the content of the consultations. RESULTS: Most enquiries to the case management
      were made by telephone. The majority of requests regarded patients with
      oncological disease (84.3 %). The largest enquiring group was composed of
      patients and relatives (40.8 %), followed by internal professionals of the
      hospital (36.1 %). Most of the enquiring persons asked for a patient's admission
      to the palliative care ward (46.4 %). The second most frequent request was for
      consultation and advice (30.9 %), followed by requests for the palliative home
      care service (13.3 %). Frequent reasons for actual admissions were the need for
      the treatment of pain, the presence of symptoms and the need for nursing care.
      More than half of the enquiries concerning admission to the palliative care ward
      were followed by an admission. CONCLUSIONS: Case management has been made public
      among the relevant target groups. Case management as described by the Case
      Management Process Model helps to identify patients likely to benefit from case
      management and palliative care services. In addition, with the help of case
      management palliative patients may be allocated to particular health care
      services.

PMID- 23116369
TI  - Rule-breaking in an anonymous situation: when people decide to deviate from
      existing rules.
AB  - The present study examined how soon people would make a decision to break
      existing rules in an anonymous situation, with particular attention paid to the
      degree of anonymity. A total of 100 participants were randomly assigned to either
      a self-reward condition or an other-reward condition, in both of which they were
      asked to flip a coin twice in each of the four coin-flip trials to win the
      assigned reward. As predicted, the results showed that only participants in the
      self-reward condition broke the assignment rules for obtaining the reward, and
      they only did so in the very last coin-flip trial. In sum, the present findings
      suggest that people do not break existing rules for material gain as soon as they
      become anonymized, but some may do so at the very last moment. 

PMID- 23116370
TI  - A lifetime of professional singing: Voice parameters and age in the Netherlands
      Radio Choir.
AB  - In professional choirs one would like to identify the incidence and severity of
      vocal problems due to ageing, and know how to influence them. The aim of the
      current study was to investigate to what extent easily obtainable voice
      parameters were age-related. From 47 singers of the Netherlands Radio Choir the
      Voice Range Profile parameters and the vibrato characteristics were measured.
      Dysphonia Severity Index (DSI) was calculated. We found that the age of male and
      female singers correlated negatively to the highest fundamental frequency and the
      Dysphonia Severity Index. No signs of slower and wider vibrato were found. These
      findings can lead to identifying adequate parameters e.g. for the ageing voice,
      useful in larger groups of professional singers.

PMID- 23116371
TI  - West Nile virus diagnosis and vaccination: using unique viral peptide sequences
      to evoke specific immune responses.
AB  - West Nile virus (WNV) infection may be associated with fever, neurologic
      disorders, and acute flaccid paralysis as a final clinical outcome. In spite of
      the numerous WNV infection outbreaks in Africa, Eurasia, Australia, and North
      America and notwithstanding an intense research effort for developing effective
      anti-WNV vaccines, currently no immunopreventive or therapeutic approaches are
      available. Moreover, antigenic cross-reactivity among flaviviruses can make
      difficult WNV serodiagnosis. Here we analyze the primary sequence of WNV
      polyprotein searching for peptide modules that might be utilized to design
      targeted diagnostic tools and anti-WNV vaccines for use in humans. To this aim,
      we applied the low-similarity hypothesis, according to which rare peptide
      sequences are more likely immunogenic than frequent peptide sequences. We report
      on a set of peptide sequences unique to the WNV, the immunogenic potential of
      which appears to be confirmed by immunological data cataloged at the Immune
      Epitope Data Base resource.

PMID- 23116372
TI  - Idealized models of protofilaments of human islet amyloid polypeptide.
AB  - Fibrils formed by assembly of human islet amyloid polypeptide (hIAPP) are found
      in most patients with type II diabetes. Structurally, these fibrils are composed
      of multiple protofilaments and are characterized by extended beta sheets,
      variable helical twists, and different morphologies. We have previously derived
      models for the hIAPP protofilament using simulations constrained by data from EPR
      spectroscopy. In the current work, these models were used as a basis for
      generating idealized hIAPP protofilaments with symmetrical geometrical properties
      using a new algorithm, MFIBRIL. We show good agreement of the idealized
      protofilaments with experimental data for amino acid side chain orientations and
      geometrical features including the inter-beta sheet distance and the
      protofilament radius. These idealized protofilaments can be used in MFIBRIL to
      generate fibril models that may be experimentally testable at the molecular
      level. MFIBRIL can also be used for building structures of any repetitive
      molecular assembly starting with a single building block obtained from any
      source.

PMID- 23116375
TI  - "Nothing endures but change".

PMID- 23116373
TI  - The native GCN4 leucine-zipper domain does not uniquely specify a dimeric
      oligomerization state.
AB  - The dimerization domain of the yeast transcription factor GCN4, one of the first
      coiled-coil proteins to be structurally characterized at high resolution, has
      served as the basis for numerous fundamental studies on alpha-helical folding.
      Mutations in the GCN4 leucine zipper are known to change its preferred
      oligomerization state from dimeric to trimeric or tetrameric; however, the wild
      type sequence has been assumed to encode a two-chain assembly exclusively. Here
      we demonstrate that the GCN4 coiled-coil domain can populate either a dimer or
      trimer fold, depending on environment. We report high-resolution crystal
      structures of the wild-type sequence in dimeric and trimeric assemblies.
      Biophysical measurements suggest populations of both oligomerization states under
      certain experimental conditions in solution. We use parallel tempering molecular
      dynamics simulations on the microsecond time scale to compare the stability of
      the dimer and trimer folded states in isolation. In total, our results suggest
      that the folding behavior of the well-studied GCN4 leucine-zipper domain is more
      complex than was previously appreciated. Our results have implications in ongoing
      efforts to establish predictive algorithms for coiled-coil folds and the
      selection of coiled-coil model systems for design and mutational studies where
      oligomerization state specificity is an important consideration.

PMID- 23116374
TI  - CAM practitioners in the Australian health workforce: an underutilized resource.
AB  - BACKGROUND: CAM practitioners are a valuable but underutilizes resource in
      Australian health care. Despite increasing public support for complementary and
      alternative medicine (CAM) little is known about the CAM workforce. Apart from
      the registered professions of chiropractic, osteopathy and Chinese medicine,
      accurate information about the number of CAM practitioners in the workforce has
      been difficult to obtain. It appears that many non-registered CAM practitioners,
      although highly qualified, are not working to their full capacity. DISCUSSION:
      Increasing public endorsement of CAM stands in contrast to the negative attitude
      toward the CAM workforce by some members of the medical and other health
      professions and by government policy makers. The marginalisation of the CAM
      workforce is evident in prejudicial attitudes held by some members of the medical
      and other health professions and its exclusion from government policy making.
      Inconsistent educational standards has meant that non-registered CAM
      practitioners, including highly qualified and competent ones, are frequently
      overlooked. Legitimising their contribution to the health workforce could
      alleviate workforce shortages and provide opportunities for redesigned job roles
      and new multidisciplinary teams. Priorities for better utilisation of the CAM
      workforce include establishing a guaranteed minimum education standard for more
      CAM occupation groups through national registration, providing interprofessional
      education that includes CAM practitioners, developing courses to upgrade CAM
      practitioners' professional skills in areas of indentified need, and increasing
      support for CAM research. SUMMARY: Marginalisation of the CAM workforce has
      disadvantaged those qualified and competent CAM practitioners who practise
      evidence-informed medicine on the basis of many years of university training.
      Legitimising and expanding the important contribution of CAM practitioners could
      alleviate projected health workforce shortages, particularly for the prevention
      and management of chronic health conditions and for health promotion.

PMID- 23116376
TI  - Engaging youths with serious mental illnesses in treatment: STARS study consumer
      recommendations.
AB  - OBJECTIVE: The purpose of this study was to identify better methods of engaging
      youths in mental health services by asking experienced mental health consumers
      for suggestions for clinicians. METHODS: 177 members of an integrated health
      plan, ranging in age from 16-84 years and diagnosed with schizophrenia,
      schizoaffective disorder, bipolar disorder, or affective psychosis, completed
      four in-depth semistructured interviews over 24 months as part of a study of
      recovery from serious mental illness. We transcribed and coded interviews,
      extracted a set of common themes addressing consumer recommendations to
      clinicians, and compared these themes across age groups. RESULTS: Five primary
      themes emerged in participants' recommendations: (1) use an age-appropriate
      approach that reflects youth culture and lifestyles; (2) foster development of
      autonomy; (3) take a personal, rather than diagnostic, approach; (4) be
      empathetic and authentic; and (5) create a safe and supportive environment.
      Consumers age 30 and older described three additional areas in which clinicians
      could contribute to youths' well being: (1) help find the right diagnosis and the
      right medication, (2) counsel youths to avoid using alcohol and drugs, and (3)
      take steps to help prevent social isolation. CONCLUSIONS: Study findings suggest
      that many strategies recommended for working with adults may benefit young
      people, but that developmentally appropriate modifications to these approaches
      are needed to foster treatment engagement among youths.

PMID- 23116378
TI  - Toward understanding the impact of occupational characteristics on the recovery
      and growth processes of peer providers.
AB  - OBJECTIVE: Peer providers experience unique recovery and growth processes. This
      study examines the relationship of these processes with multiple occupational
      characteristics related to peer work. Outcomes are examined using positive
      psychology concepts: psychological well-being, posttraumatic growth, and
      generativity, as well as established recovery and empowerment measures. METHOD:
      Thirty peer providers employed in a variety of mental-health agencies
      participated in the study and completed standardized measures of recovery and
      growth processes. Multiple past and present occupational characteristics were
      identified and coded based on a semistructured interview and a background
      questionnaire. RESULTS: Multivariate analyses revealed a significant association
      between participants' generativity and past participation in peer-support/self
      help groups, as well as past work in a helping profession. No associations were
      found between the characteristics of participants' present peer jobs and the
      examined recovery and growth processes. CONCLUSIONS AND IMPLICATIONS FOR
      PRACTICE: The present findings have implications for the expansion of the peer
      provider workforce. They suggest that encouraging and enabling peer-support
      groups and peer-run organizations may have positive impact on the generativity of
      peer providers, and may draw generative individuals to this emerging occupational
      modality of mental-health recovery oriented service. Study findings underscore
      the need for future research on recovery processes from the perspective of
      positive psychology and highlight the value of peer exposure as a catalyst of
      recovery and growth.

PMID- 23116377
TI  - Reliability and validity of a treatment adherence measure for child psychiatric
      rehabilitation.
AB  - OBJECTIVE: Treatment adherence, defined as the degree to which practitioners
      implemented prescribed program principles and activities and avoided proscribed
      activities, has been an area of growing interest in mental health services for
      children with severe emotional and behavioral disorders. This study evaluated the
      reliability and validity of a treatment adherence measure for child psychiatric
      rehabilitation (CPSR). METHODS: Parents of children receiving CPSR (n = 79) or
      psychotherapy (n = 27) completed the Children's Psychosocial Rehabilitation
      Treatment Adherence Measure (CTAM) and a measure of 2-week session impact.
      Psychiatric rehabilitation (PSR) supervisors identified PSR practitioners with
      reputations for high or low adherence to the model. The CTAM's discriminant
      validity was assessed by using known-groups procedures and predictive validity by
      examining its relationship to 2-week session impact. RESULTS: The CTAM
      demonstrated excellent internal consistency (alpha = .92), discriminant validity
      (p = .002, d = .72; p = .021, d = .59), and predictive validity (B = 2.24, SE =
      .31, p < .001), accounting for 28% of the child-level variance in 2-week session
      impact. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Findings suggest the CTAM is a
      reliable and valid measure of treatment adherence for CPSR programs with a skill
      teaching focus. Providers and agencies should take steps to enhance treatment
      adherence because it may be an important predictor of children's short-term
      response to CPSR.

PMID- 23116379
TI  - How does stigma affect work in people with serious mental illnesses?
AB  - OBJECTIVES: How does stigma influence whether people with serious mental illness
      work? We examine the relationship of public stigma (the effects that occur when
      people with mental illness endorse the common prejudice of mental illness) and
      self-stigma (the results of people with psychiatric disorders internalizing
      prejudice) on current and lifetime histories of work. METHODS: Eighty-five
      persons with serious mental illness reported current work history (i.e., in the
      past 3 months and in the past year) and lifetime work history (i.e., "have you
      ever worked?"). They also completed measures of self- and public stigma, focusing
      on the stereotypes of responsibility and dangerousness. RESULTS: Endorsement of
      public stigma was shown to be significantly associated with lifetime history of
      work and self-stigma with current history. The dangerousness cluster of public
      stigma was specifically associated with lifetime work. We also tested a
      hierarchical model of self-stigma: that people need to first be aware of the
      prejudice, then agree to it, next apply it to themselves, and finally experience
      some harm to self-esteem. Only the latter stages of self-stigma-apply and harm
      were correlated with current work. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE:
      Implications of these findings for meaningfully impacting stigma change are
      considered. In particular, we discuss ways to change public and self-stigma in
      order to enhance work.

PMID- 23116380
TI  - Employer attitudes about criminal histories.
AB  - OBJECTIVE: Although the individual placement and support (IPS) approach has
      demonstrated superior competitive employment outcomes for people with severe
      mental illness, practitioners report that job obtainment for people with criminal
      convictions is particularly challenging. The current study examined employer
      hiring decisions and attitudes regarding job applicants with felonies. The main
      purpose of the study was to identify the percentage of employers who had
      knowingly hired applicants with felonies, and if the hiring patterns differed by
      employer type. METHOD: Twelve employment specialists from nine states interviewed
      128 employers about their past hiring practices. Two IPS trainers coordinated the
      project with the specialists. RESULTS: Survey findings did not support common
      assumptions held by employment specialists about employer attitudes. Sixty-three
      percent of employers surveyed said that they had knowingly hired at least one
      person with a felony conviction. Further, few businesses had written policies
      that would prohibit the hiring of people with felony convictions. CONCLUSIONS AND
      IMPLICATIONS FOR PRACTICE: Employers' reported reasons for having hired
      individuals with felony convictions provide a framework to help jobseekers
      improve their prospects for favorable hiring decisions. Employers suggested that
      relationships with employment specialists can also facilitate the hiring of
      applicants with felonies.

PMID- 23116381
TI  - Work-ordered day as a catalyst of competitive employment success.
AB  - OBJECTIVE: This purpose of this study was to determine whether participation in
      the Work-Ordered Day program of the Clubhouse model has a positive effect on
      vocational outcomes. METHOD: The longitudinal study followed a group of
      individuals with severe mental illness who were randomly assigned either to a
      Clubhouse program or a Program of Assertive Community Treatment team. Study
      participants were tracked for 135 weeks. These analyses evaluated the
      relationship between Work-Ordered Day participation and employment duration for
      the 43 study participants enrolled in the Clubhouse program who were active
      throughout the study and competitively employed during the study. RESULTS:
      Participation in the Work-Ordered Day program had a significant positive impact
      on average duration of employment. On average, a 1-hr increase in participation
      prior to employment led to an increase of 2.3 weeks in competitive employment.
      CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Participants with more Work-Ordered
      Day program participation prior to employment had significantly longer average
      competitive employment duration even when controlling for prior work history.
      Participation in the Work-Ordered Day program is likely to improve work
      readiness. Further research is warranted to study which elements of the program
      may foment employment success. This could lead to increased implementation of the
      Work-Ordered Day program and its elements as precursors to employment for adults
      with severe mental illness.

PMID- 23116382
TI  - Lifestyle coaching's effect on 6-month follow-up in recently homeless substance
      dependent veterans: a randomized study.
AB  - OBJECTIVE: Behaviors and activities consistent with "healthy" lifestyles (i.e.,
      leisure and recreational activities, social and family interactions, coping
      behaviors) have been shown to be related to prolonged substance dependence
      recovery. However, there has been little focus on systematically capitalizing on
      this association in treatment to improve relapse rates. The goal of this study
      was to determine if the inclusion of healthy lifestyle coaching, that is the
      encouragement of specific behaviors in a therapeutic setting, could impact time
      to relapse. METHODS: Fifty-six veterans who were recently discharged from a
      Veterans Administration (VA) homeless Domiciliary Residential Rehabilitation and
      Treatment Program and were substance dependent were evaluated over a 6-month
      follow-up period. Using a partially randomized design, three groups were
      evaluated: 1) those followed by a therapist and coached to increase healthy
      behaviors, 2) those followed by a therapist and receiving only emotional support,
      and 3) those not followed by a therapist. Survival analyses and nonparametric
      evaluations were performed. RESULTS: Coached consumers had longer latency to
      relapse than noncoached and relapsed at a lower rate than those not followed by a
      therapist. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Therapeutic interventions
      which focus on increasing healthy behaviors chosen by the consumer can be an
      important component of sustained recovery from substance dependence.

PMID- 23116383
TI  - Wellness Recovery Action Planning (WRAP) in self-help and mutual support groups.
AB  - OBJECTIVE: The aim of this research was to assess the relevance and impact of
      Wellness Recovery Action Planning (WRAP) in group settings, as a tool for self
      management and wellness planning by individuals with mental-health problems. This
      paper reports on the impact on participants who trained as facilitators and
      delivered WRAP training to others within the organizations studied. METHOD: Eight
      WRAP facilitators took part in interviews and focus groups. RESULTS: The WRAP
      facilitators reported a positive impact on their well-being, from learning more
      about recovery, developing improved self-awareness, to integrating a WRAP
      approach into daily life. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Delivering
      WRAP training to groups can make a positive contribution to the well-being of
      facilitators themselves. Involving people with lived experience in the delivery
      of WRAP groups in this setting further promoted the recovery journey of
      facilitators.

PMID- 23116384
TI  - Peer employees' and clinicians' perceptions of public mental illness stigma and
      discrimination.
AB  - OBJECTIVE: Stigma and discrimination against people with mental illnesses are
      serious problems that can lead to many negative effects. This study examined
      providers' awareness of consumers' daily lived experience of discrimination.
      METHOD: We surveyed 51 peer employees and 52 licensed clinicians to learn how
      they viewed the extent of public stigma and discrimination. RESULTS: Clinicians,
      women, and those who had observed a friend with a mental illness treated unfairly
      perceived significantly higher levels of public discrimination than did their
      counterparts (adjusted R2 = .399, p < .001). Men's perceptions of public
      discrimination were more strongly affected by personal contact. CONCLUSIONS AND
      IMPLICATIONS FOR PRACTICE: Mental health providers are uniquely situated to help
      consumers deal with the effects of discrimination and should incorporate this
      issue into their clinical practice. Further research should examine the reasons
      for differences in perception and how these differences relate to provider
      behavior and consumer outcomes.

PMID- 23116385
TI  - Integration of a peer provider in a mental health clinic: perspectives from a
      peer provider and a clinic director.

PMID- 23116386
TI  - Getting the message right.

PMID- 23116390
TI  - Amelogenesis imperfecta: a conservative and progressive adhesive treatment
      concept.
AB  - OBJECTIVE: The aim of this study was to present a case report of a patient
      affected by amelogenesis imperfecta showing a possible minimal and conservative
      adhesive treatment approach. CLINICAL PROCEDURE: A treatment philosophy of
      amelogenesis imperfecta is illustrated by means of a case report of a 14-year-old
      boy who consulted us for a full mouth rehabilitation. DISCUSSION: This clinical
      report describes step by step how to manage a case of amelogenesis imperfecta
      from childhood over time. SIGNIFICANCE: This kind of minimally invasive,
      progressive approach allows the conservation of maximum tooth substance together
      with an acceptable esthetic outcome.

PMID- 23116391
TI  - D-amino acid oxidase inhibitors as a novel class of drugs for schizophrenia
      therapy.
AB  - Over the years, accumulating evidence has indicated that D-serine represents the
      endogenous ligand for the glycine modulatory binding site on the NR1 subunit of N
      methyl-D-aspartate receptors in various brain areas. Cellular concentrations of D
      serine are regulated by synthesis due to the enzyme serine racemase
      (isomerization reaction) and by degradation due to the same enzyme(elimination
      reaction) as well as by the FAD-containing flavoenzyme D-amino acid oxidase
      (DAAO, oxidative deamination reaction).Several findings have linked low levels of
      D-serine to schizophrenia: D-serine concentrations in serum and cerebrospinal
      fluid have been reported to be decreased in schizophrenia patients while human
      DAAO activity and expression are increased; oral administration of D-serine
      improved positive, negative, and cognitive symptoms of schizophrenia as add-on
      therapy to typical and atypical antipsychotics.This evidence indicates that
      increasing NMDA receptor function, perhaps by inhibiting DAAO-induced degradation
      of D-serine may alleviate symptoms in schizophrenic patients. Furthermore, it has
      been suggested that co-administration of D-serine with a human DAAO inhibitor may
      be a more effective means of increasing D-serine levels in the brain. Here, we
      present an overview of the current knowledge of the structure-function
      relationships in human DAAO and of the compounds recently developed to inhibit
      its activity (specifically the ones recently exploited for schizophrenia
      treatment).

PMID- 23116392
TI  - Inhibitor design for monoamine oxidases.
AB  - Flavin-containing monoamine oxidases (MAO A and MAO B) located on the outer
      membrane of mitochondria oxidise amines and generate hydrogen peroxide.
      Inhibitors alleviate depression by increasing neurotransmitter levels in the
      brain. Elevation of neurotransmitters,although an established outcome, is a
      delicate balance because complete lack of MAO A is associated with aggression and
      combination of monoamine oxidase inhibitors with reuptake inhibitors can result
      in serotonin toxicity. MAO in the periphery is essential for protection against
      biogenic amines, so inhibition there is an undesirable side effect both of
      antidepressants and drugs for other targets.MAO also metabolizes many amine
      drugs, an important factor in pharmacokinetics. This review summarises the
      structure, assay and regulation of MAO. The importance of reliable inhibition
      data properly analysed for these flavoenzymes is emphasised. It describes some
      current drugs and how new compounds that inhibit MAO are emerging from structure
      based drug design.

PMID- 23116394
TI  - Riboflavin analogs as antiinfectives: occurrence, mode of action, metabolism and
      resistance.
AB  - Antimetabolites are molecules, which are structurally similar to molecules needed
      to carry out primary metabolic reactions.The inhibitory activity of an
      antimetabolite depends on its successful competition with the natural substrate,
      ligand, modulator or cofactor of a given biomolecule. Antimetabolites are
      indispensable as molecular tools in order to understand biological processes.
      Beyond that,antimetabolites have a large variety of applications in the
      pharmaceutical and food industries. The identification of the structural
      riboflavin(vitamin B2) analog roseoflavin in Streptomyces davawensis demonstrates
      that anti-vitamins/cofactor analogs may serve as lead structures for the
      development of novel antibiotics. The latter is supported by the recent finding
      that roseoflavin had a profound inhibiting effect on the growth and infectivity
      of the human bacterial pathogen Listeria monocytogenes at very low
      concentrations. Roseoflavin is studied in our laboratory as a model compound. We
      investigate the biosynthesis, the possible large-scale production, the
      metabolization,the mechanism of action and the resistance mechanism of the
      producer organism in order to pave the way for the structured analysis of other
      vitamin analogs yet to be discovered. These compounds hopefully will help to
      replenish the arsenal of antimicrobials urgently needed to fight multiresistant
      bacterial pathogens.

PMID- 23116393
TI  - Is renalase a novel player in catecholaminergic signaling? The mystery of the
      catalytic activity of an intriguing new flavoenzyme.
AB  - Renalase is a flavoprotein recently discovered in humans, preferentially
      expressed in the proximal tubules of the kidney and secreted in blood and urine.
      It is highly conserved in vertebrates, with homologs identified in eukaryotic and
      prokaryotic organisms. Several genetic, epidemiological, clinical and
      experimental studies show that renalase plays a role in the modulation of the
      functions of the cardiovascular system, being particularly active in decreasing
      the catecholaminergic tone, in lowering blood pressure and in exerting a
      protective action against myocardial ischemic damage. Deficient renalase
      synthesis might be the cause of the high occurrence of hypertension and adverse
      cardiac events in kidney disease patients. Very recently, recombinant human
      renalase has been structurally and functionally characterized in vitro. Results
      show that it belongs to the p-hydroxybenzoate hydroxylase structural family of
      flavoenzymes, contains non-covalently bound FAD with redox features suggestive of
      a dehydrogenase activity, and is not a catecholamine-degrading enzyme,either
      through oxidase or NAD(P)H-dependent monooxygenase reactions. The biochemical
      data now available will hopefully provide the basis for a systematic and rational
      quest toward the identification of the reaction catalyzed by renalase and of the
      molecular mechanism of its physiological action, which in turn are expected to
      favor the development of novel therapeutic tools for the treatment of kidney and
      cardiovascular diseases.

PMID- 23116396
TI  - Methylenetetrahydrofolate reductase: biochemical characterization and medical
      significance.
AB  - Methylenetetrahydrofolate reductase (MTHFR) catalyzes the reduction of 5,10
      methylenetetrahydofolate (CH2-H4folate) to 5-methyltetrahydrofolate (CH3
      H4folate). The enzyme employs a noncovalently-bound flavin adenine dinucleotide
      (FAD), which accepts reducing equivalents from NAD(P)H and transfers them to CH2
      H4folate. The reaction provides the sole source of CH3-H4folate, which is
      utilized by methionine synthase in the synthesis of methionine from homocysteine.
      MTHFR plays a key role in folate metabolism and in the homeostasis of
      homocysteine; mutations in the enzyme lead to hyperhomocyst(e)inemia. A common
      C677T polymorphism in MTHFR has been associated with an increased risk for the
      development of cardiovascular disease, Alzheimer's disease, and depression in
      adults, and of neural tube defects in the fetus. The mutation also confers
      protection for certain types of cancers. This review presents the current
      knowledge of the enzyme, its biochemical characterization, and medical
      significance.

PMID- 23116397
TI  - Redox proteins as targets for drugs development against pathogens.
AB  - Antimicrobial drug resistance in pathogens is an increasing human health problem.
      The rapid loss of effectiveness in antibiotics treatments and the accumulation of
      multi-resistant microbial strains are increasing worldwide threats. Moreover,
      several infectious diseases have been neglected for years and new antimicrobial
      treatments are lacking. In other cases, complexity of infectious organisms has
      exceeded the efforts to find new drugs to control them. Thus, strategies for the
      proper development of specific drugs are critically needed. Redox metabolism has
      already been proved to be a useful target for drug development. During the last
      years a significant number of electron carriers, enzymes, proteins and protein
      complexes have been studied and some of them were found to be essential for
      survival of several microbial pathogens. This review will focus on three major
      redox metabolic pathways which may provide promising strategies to fight against
      pathogens: the non-mevalonate pathway for isoprenoids biosynthesis, the iron
      metabolism and the iron-sulfur proteins.The common attractive link of all these
      processes is the plant-type ferredoxin-NADP+ reductase, an enzyme that
      participates in numerous electron transfer reactions and has no homologous enzyme
      in humans. Research in these redox pathways will open new perspectives for the
      rational design of drugs against infectious diseases.

PMID- 23116395
TI  - Targeting UDP-galactopyranose mutases from eukaryotic human pathogens.
AB  - UDP-Galactopyranose mutase (UGM) is a unique flavin-dependent enzyme that
      catalyzes the conversion of UDP-galactopyranose(UDP-Galp) to UDP-galactofuranose
      (UDP-Galf). The product of this reaction is the precursor to Galf, a major
      component of the cell wall and of cell surface glycoproteins and glycolipids in
      many eukaryotic and prokaryotic human pathogens. The function of UGM is important
      in the virulence of fungi, parasites, and bacteria. Its role in virulence and its
      absence in humans suggest that UGM is an ideal drug target. Significant
      structural and mechanistic information has been accumulated on the prokaryotic
      UGMs; however, in the past few years the research interest has shifted to UGMs
      from eukaryotic human pathogens such as fungi and protozoan parasites. It has
      become clear that UGMs from prokaryotic and eukaryotic organisms have different
      structural and mechanistic features. The amino acid sequence identity between
      these two classes of enzymes is low, resulting in differences in oligomeric
      states, substrate binding, active site flexibility, and interaction with redox
      partners. However, the unique role of the flavin cofactor in catalysis is
      conserved among this enzyme family. In this review, recent findings on eukaryotic
      UGMs are discussed and presented in comparison with prokaryotic UGMs.

PMID- 23116399
TI  - Target sites for the design of anti-trypanosomatid drugs based on the structure
      of dihydroorotate dehydrogenase.
AB  - Trypanosomatids consist of a large group of flagellated parasitic protozoa,
      including parasites from the genera Leishmania and Trypanosoma, responsible for
      causing infections in millions of humans worldwide and for which currently no
      appropriate therapy is available. The significance of pyrimidines in cellular
      metabolism makes their de novo and salvage pathways ideal druggable targets for
      pharmacological intervention and open an opportunity for pharmaceutical
      innovation. In the current review, we discuss the merits in targeting the enzyme
      dihydroorotate dehydrogenase (DHODH), a flavin-dependent enzyme that catalyzes
      the fourth and only redox step in pyrimidine de novo biosynthesis, as a strategy
      for the development of efficient therapeutic strategies for trypanosomatid
      related diseases.We also describe the advances and perspectives from the
      structural biology point of view in order to unravel the structure-function
      relationship of trypanosomatid DHODHs, and to identify and validate target sites
      for drug development.

PMID- 23116398
TI  - Chemical nature and reaction mechanisms of the molybdenum cofactor of xanthine
      oxidoreductase.
AB  - Xanthine oxidoreductase (XOR), a complex flavoprotein, catalyzes the metabolic
      reactions leading from hypoxanthine to xanthine and from xanthine to urate, and
      both reactions take place at the molybdenum cofactor. The enzyme is a target of
      drugs for therapy of gout or hyperuricemia. We review the chemical nature and
      reaction mechanisms of the molybdenum cofactor of XOR, focusing on molybdenum
      dependent reactions of actual or potential medical importance, including nitric
      oxide (NO) synthesis. It is now generally accepted that XOR transfers the water
      exchangeable -OH ligand of the molybdenum atom to the substrate. The hydroxyl
      group at OH-Mo(IV) can be replaced by urate, oxipurinol and FYX-051 derivatives
      and the structures of these complexes have been determined by xray
      crystallography under anaerobic conditions. Although formation of NO from nitrite
      or formation of xanthine from urate by XOR ischemically feasible, it is not yet
      clear whether these reactions have any physiological significance since the
      reactions are catalyzed at a slow rate even under anaerobic conditions.

PMID- 23116400
TI  - The oxido-reductase activity of the apoptosis inducing factor: a promising
      pharmacological tool?
AB  - The apoptosis inducing factor (AIF) was first discovered as a caspase-independent
      apoptosis effector that promoted cell death upon release from the mitochondria
      (triggered by pro-apoptotic stimuli) and relocalization into the nucleus, where
      it promotes chromatin condensation and DNA fragmentation. AIF is a mammalian
      mitochondrial FAD-dependent flavoenzyme, ubiquitous in vertebrate cells,and with
      orthologs in all eukaryotes. Beyond its role in apoptosis AIF has additional
      functions in mitochondria, mainly related with the redox function of its flavin
      adenine dinucleotide cofactor (FAD), which despite being poorly understood are
      vital. Thus, defects in AIF trigger major dysfunctions in oxidative
      phosphorylation, and cause severe illnesses related with neurodegeneration as a
      consequence of mitochondriopathies. AIF folds in three modules: a FAD-binding, a
      nicotine adenine dinucleotide (NADH)-binding and a C-terminal modules. Upon
      reduction of the flavin cofactor by NADH, conformational changes leading to AIF
      dimerization are proposed as a key early event in the mitochondrial
      sensing/signaling functions of AIF. The recent interest in the design of new
      therapies to modulate caspase-independent apoptosis pathways also makes AIF a
      potential pharmacological target to treat pathological disorders related with AIF
      dependent mitochondriopathies. Therefore, the first step in this direction must
      be to understand the molecular basis of the AIF redox reactions and their
      relationship with the apoptotic function. Here, we examine recent research
      towards the molecular mechanisms linked to the AIF oxido-reduction properties.

PMID- 23116401
TI  - The prokaryotic FAD synthetase family: a potential drug target.
AB  - Disruption of cellular production of the flavin cofactors, flavin adenine
      mononucleotide (FMN) and flavin adenine dinucleotide(FAD) will prevent the
      assembly of a large number of flavoproteins and flavoenzymes involved in key
      metabolic processes in all types of organisms. The enzymes responsible for FMN
      and FAD production in prokaryotes and eukaryotes exhibit various structural
      characteristics to catalyze the same chemistry, a fact that converts the
      prokaryotic FAD synthetase (FADS) in a potential drug target for the development
      of inhibitors endowed with anti-pathogenic activity. The first step before
      searching for selective inhibitors of FADS is to understand the structural and
      functional mechanisms for the riboflavin kinase and FMN adenylyltransferase
      activities of the prokaryotic enzyme, and particularly to identify their
      differential functional characteristics with regard to the enzymes performing
      similar functions in other organisms, particularly humans. In this paper, an
      overview of the current knowledge of the structure-function relationships in
      prokaryotic FADS has been presented, as well as of the state of the art in the
      use of these enzymes as drug targets.

PMID- 23116402
TI  - Biosynthesis of flavin cofactors in man: implications in health and disease.
AB  - The primary role of the water-soluble vitamin B2, i.e. riboflavin, in cell
      biology is connected with its conversion into FMN and FAD, the cofactors of a
      large number of dehydrogenases, reductases and oxidases involved in energetic
      metabolism, redox homeostasis and protein folding as well as in diverse
      regulatory events. Deficiency of riboflavin in men and experimental animal models
      has been linked to several diseases, including neuromuscular and neurological
      disorders and cancer. Riboflavin at pharmacological doses has been shown to play
      unexpected and incompletely understood regulatory roles. Besides a summary on
      riboflavin uptake and a survey on riboflavin-related diseases, the main focus of
      this review is on discovery and characterization of FAD synthase (EC 2.7.7.2) and
      other components of the cellular networks that ensure flavin cofactor
      homeostasis.Special attention is devoted to the problem of sub-cellular
      compartmentalization of cofactor synthesis in eukaryotes, made possible by the
      existence of different FAD synthase isoforms and specific molecular components
      involved in flavin trafficking across sub-cellular membranes.Another point
      addressed in this review is the mechanism of cofactor delivery to nascent apo
      proteins, especially those localized into mitochondria, where they integrate FAD
      in a process that involves additional mitochondrial protein(s) still to be
      identified. Further efforts are necessary to elucidate the role of riboflavin/FAD
      network in human pathologies and to exploit the structural differences between
      human and microbial/fungal FAD synthase as the rational basis for developing
      novel antibiotic/antimycotic drugs.

PMID- 23116404
TI  - Flavoproteins and flavoenzymes with biomedical and therapeutic impact.

PMID- 23116405
TI  - Combined blood transfusion and hydroxycarbamide in children with sickle cell
      anaemia.

PMID- 23116403
TI  - 1,4-naphthoquinones and other NADPH-dependent glutathione reductase-catalyzed
      redox cyclers as antimalarial agents.
AB  - The homodimeric flavoenzyme glutathione reductase catalyzes NADPH-dependent
      glutathione disulfide reduction. This reaction is important for keeping the redox
      homeostasis in human cells and in the human pathogen Plasmodium falciparum.
      Different types of NADPH-dependent disulfide reductase inhibitors were designed
      in various chemical series to evaluate the impact of each inhibition mode on the
      propagation of the parasites. Against malaria parasites in cultures the most
      potent and specific effects were observed for redox-active agents acting as
      subversive substrates for both glutathione reductases of the Plasmodium-infected
      red blood cells. In their oxidized form, these redox-active compounds are reduced
      by NADPH-dependent flavoenzyme-catalyzed reactions in the cytosol of infected
      erythrocytes. In their reduced forms, these compounds can reduce molecular oxygen
      to reactive oxygen species, or reduce oxidants like methemoglobin, the major
      nutrient of the parasite, to indigestible hemoglobin. Furthermore, studies on a
      fluorinated suicide-substrate of the human glutathione reductase indicate that
      the glutathione reductase-catalyzed bioactivation of 3-benzylnaphthoquinones to
      the corresponding reduced 3-benzoyl metabolites is essential for the observed
      antimalarial activity. In conclusion, the antimalarial lead naphthoquinones are
      suggested to perturb the major redox equilibria of the targeted cells. These
      effects result in developmental arrest of the parasite and contribute to the
      removal of the parasitized erythrocytes by macrophages.

PMID- 23116406
TI  - Triple-negative breast cancer and PTEN (phosphatase and tensin homologue) loss
      are predictors of BRCA1 germline mutations in women with early-onset and familial
      breast cancer, but not in women with isolated late-onset breast cancer.
AB  - INTRODUCTION: Given that breast cancers in germline BRCA1 carriers are
      predominantly estrogen-negative and triple-negative, it has been suggested that
      women diagnosed with triple-negative breast cancer (TNBC) younger than 50 years
      should be offered BRCA1 testing, regardless of family cancer characteristics.
      However, the predictive value of triple-negative breast cancer, when taken in the
      context of personal and family cancer characteristics, is unknown. The aim of
      this study was to determine whether TNBC is a predictor of germline BRCA1
      mutations, in the context of multiple predictive factors. METHODS: Germline
      mutations in BRCA1 and BRCA2 were analyzed by Sanger sequencing and multiple
      ligation-dependent probe amplification (MLPA) analysis in 431 women from the
      Malaysian Breast Cancer Genetic Study, including 110 women with TNBC. Logistic
      regression was used to identify and to estimate the predictive strength of major
      determinants. Estrogen receptor (ER) and phosphatase and tensin homologue (PTEN)
      status were assessed and included in a modified Manchester scoring method.
      RESULTS: Our study in an Asian series of TNBC patients demonstrated that 27
      (24.5%) of 110 patients have germline mutations in BRCA1 (23 of 110) and BRCA2
      (four of 110). We found that among women diagnosed with breast cancer aged 36 to
      50 years but with no family history of breast or ovarian cancer, the prevalence
      of BRCA1 and BRCA2 mutations was similar in TNBC (8.5%) and non-TNBC patients
      (6.7%). By contrast, in women diagnosed with breast cancer, younger than 35
      years, with no family history of these cancers, and in women with a family
      history of breast cancer, the prevalence of mutations was higher in TNBC compared
      with non-TNBC (28.0% and 9.9%; P = 0.045; and 42.1% and 14.2%; P < 0.0001,
      respectively]. Finally, we found that incorporation of estrogen-receptor and TNBC
      status improves the sensitivity of the Manchester Scoring method (42.9% to
      64.3%), and furthermore, incorporation of PTEN status further improves
      sensitivity (42.9% to 85.7%). CONCLUSIONS: We found that TNBC is an important
      criterion for highlighting women who may benefit from genetic testing, but that
      this may be most useful for women with early-onset breast cancer (35 years or
      younger) or with a family history of cancers. Furthermore, addition of TNBC and
      PTEN status improves the sensitivity of the Manchester scoring method and may be
      particularly important in the Asian context, where risk-assessment models
      underestimate the number of mutation carriers.

PMID- 23116407
TI  - Temperature dependence of evolutionary diversification: differences between two
      contrasting model taxa support the metabolic theory of ecology.
AB  - Biodiversity patterns are largely determined by variation of diversification
      rates across clades and geographic regions. Although there are multiple reasons
      for this variation, it has been hypothesized that metabolic rate is the crucial
      driver of diversification of evolutionary lineages. According to the metabolic
      theory of ecology (MTE), metabolic rate - and consequently speciation - is driven
      mainly by body size and environmental temperature. As environmental temperature
      affects metabolic rate in ecto- and endotherms differently, its impact on
      diversification rate should also differ between the two types of organisms.
      Employing two independent approaches, we analysed correlates of speciation rates
      and, ultimately, net diversification rates for two contrasting taxa: plethodontid
      salamanders and carnivoran mammals. Whereas in the ectothermic plethodontids
      speciation rates positively correlated with environmental temperature, in the
      endothermic carnivorans a reverse, negative correlation was detected. These
      findings comply with predictions of the MTE and suggest that similar geographic
      patterns of biodiversity across taxa (e.g. ecto- and endotherms) might have been
      generated by different ecological and evolutionary processes.

PMID- 23116408
TI  - Histological chronic prostatitis and high-grade prostate intra-epithelial
      neoplasia do not influence urinary prostate cancer gene 3 score.
AB  - What's known on the subject? and What does the study add? While the relationship
      between PCA3 score and clinical or histological prostatitis was quite proven even
      in small patient groups, conversely the relationship between PCA3 score and HG
      PIN is still under debate. We demonstrated in a large series (432 patients) that
      histologically documented chronic prostatitis and HG-PIN have similar PCA3 scores
      to patients with BPH and/or normal parenchyma at biopsy. OBJECTIVE: To determine
      whether histological chronic prostatitis and high-grade prostate intra-epithelial
      neoplasia (HG-PIN) influence the prostate cancer gene 3 (PCA3) score in Italian
      patients with an elevated prostate-specific antigen (PSA) level and a negative
      digital rectal examination (DRE) who were undergoing a first or repeat prostate
      biopsy. PATIENTS AND METHODS: A urinary PCA3 test was prospectively performed in
      432 consecutive patients who were admitted to Gradenigo Hospital (Turin, Italy)
      between January and December 2011 and scheduled for first or repeat prostate
      biopsy as a result of an elevated PSA level and negative DRE. A comparison of the
      PCA3 score and patients with a negative biopsy (normal parenchyma, benign
      prostatic hyperplasia, chronic prostatitis, HG-PIN) or positive biopsy was
      performed. RESULTS: PCA3 median (range) scores varied significantly (P < 0.001)
      in men with a negative vs positive biopsy: 33 (2-212) and 66 (5-324),
      respectively. By contrast, men with chronic prostatitis and HG-PIN showed no
      significant difference with respect to PCA3 score compared to other negative
      biopsy patients. No correlation was found between the number of positive cores
      for chronic prostatitis, HG-PIN and PCA3 score. Of all patients with a positive
      biopsy, 23 (20%) of 114 men had a PCA3 score <= 35. In total, 79 (40%) of 197 men
      with a negative biopsy (normal parenchyma and benign prostatic hyperplasia), 24
      (37.5%) of 64 men with chronic prostatitis and 19 (39.6%) of 48 men with HG-PIN
      had a PCA3 score >35. CONCLUSION: At this early stage of clinical evaluation,
      cancer specificity of the urinary PCA3 test appears to be maintained in the face
      of chronic prostatitis and HG-PIN.

PMID- 23116409
TI  - A comparison of 4beta-hydroxycholesterol : cholesterol and 6beta-hydroxycortisol
      : cortisol as markers of CYP3A4 induction.
AB  - AIM: To compare plasma 4beta-hydroxycholesterol : cholesterol with urinary 6beta
      hydroxycortisol : cortisol as markers of cytochrome P4503A4 activity before and
      after treatment with rifampicin for 2 weeks. METHOD: 6beta-hydroxycortisol and
      cortisol were determined by liquid chromatography tandem mass spectrometry and
      4beta-hydroxycholesterol was determined by gas chromatography-mass spectrometry
      in three groups of healthy volunteers. RESULTS: Induction ratios for 6beta
      hydroxycortisol : cortisol were 1.8, 3.9 and 4.5 for 20 mg day(-1) , 100 mg day(
      1) or 500 mg day(-1) of rifampicin, respectively. The corresponding ratios for
      4beta-hydroxycholesterol : cholesterol were 1.5, 2.4 and 3.8. CONCLUSIONS: Plasma
      4beta-hydroxycholesterol : cholesterol gave similar induction ratios to urinary
      6beta-hydroxycortisol : cortisol.

PMID- 23116411
TI  - Methicillin-resistant Staphylococcus aureus nasal carriage among patients
      receiving hemodialysis in Taiwan: prevalence rate, molecular characterization and
      de-colonization.
AB  - BACKGROUND: Staphylococcus aureus, particularly methicillin resistant (MRSA), is
      a common pathogen among patients receiving hemodialysis. To evaluate nasal
      carriage, molecular characterization and effectiveness of decolonization of MRSA
      among patients receiving hemodialysis in Taiwan, we conducted this study.
      METHODS: From January to June 2011, two nasal samplings with a 3-month interval
      were obtained from patients undergoing hemodialysis in a medical center (CGMH),
      and in a local hospital (YMH) and sent for detection of MRSA. For MRSA carriers,
      decolonization procedures were administered. All patients in CGMH were observed
      if MRSA infections occurred during the study period. RESULTS: A total of 529
      nasal specimens (265 from CGMH and 264 from YMH) were collected from 296 patients
      (161 from CGMH and 135 from YMH). 233 patients participated in both surveys.
      Average one-time point MRSA carriage rate was 3.8%, and the rate was up to 6.9%
      for those with two-time point surveys. No additional significant factor for MRSA
      carriage was identified. Seventy percent of the 20 colonizing MRSA isolates,
      though categorized as healthcare-associated strains epidemiologically, shared
      common molecular characteristics of the local community-associated strains. Only
      one of the 20 MRSA-colonized patients failed decolonization and had persistent
      colonization, while without any intervention, 17 (61%) of 28 patients with
      methicillin-sensitive S. aureus colonization in the first survey had persistent
      colonization of a genetically indistinguishable strain. Within the study period,
      two patients (1.24%) in CGMH, one with MRSA colonization (9.1%), developed MRSA
      infection. CONCLUSION: A substantial proportion of patients receiving
      hemodialysis in Taiwan had MRSA colonization, mostly genetically community
      strains. Decolonization procedures may effectively eliminate MRSA colonization
      and might reduce subsequent MRSA infection in these patients.

PMID- 23116412
TI  - An automated plasma protein fractionation design: high-throughput perspectives
      for proteomic analysis.
AB  - BACKGROUND: Human plasma, representing the most complete record of the individual
      phenotype, is an appealing sample for proteomics analysis in clinical
      applications. Up to today, the major obstacle in a proteomics study of plasma is
      the large dynamic range of protein concentration and the efforts of many
      researchers focused on the resolution of this important drawback. FINDINGS: In
      this study, proteins from pooled plasma samples were fractionated according to
      their chemical characteristics on a home-designed SPE automated platform. The
      resulting fractions were digested and further resolved by reversed-phase liquid
      chromatography coupled with MALDI TOF/TOF mass spectrometry. A total of 712
      proteins were successfully identified until a concentration level of ng/mL.
      Pearson correlation coefficient was used to test reproducibility. CONCLUSIONS:
      Our multidimensional fractionation approach reduced the analysis time (2 days are
      enough to process 16 plasma samples filling a 96-well plate) over the
      conventional gel-electrophoresis or multi-LC column based methods. The robotic
      processing, avoiding contaminants or lack of sample handling skill, promises
      highly reproducible specimen analyses (more than 85% Pearson correlation). The
      automated platform here presented is flexible and easily modulated changing
      fractioning elements or detectors.

PMID- 23116413
TI  - Working memory for pitch, timbre, and words.
AB  - Aiming to further our understanding of fundamental mechanisms of auditory working
      memory (WM), the present study compared performance for three auditory materials
      (words, tones, timbres). In a forward recognition task (Experiment 1)
      participants indicated whether the order of the items in the second sequence was
      the same as in the first sequence. In a backward recognition task (Experiment 2)
      participants indicated whether the items of the second sequence were played in
      the correct backward order. In Experiment 3 participants performed an
      articulatory suppression task during the retention delay of the backward task. To
      investigate potential length effects the number of items per sequence was
      manipulated. Overall findings underline the benefit of a cross-material
      experimental approach and suggest that human auditory WM is not a unitary system.
      Whereas WM processes for timbres differed from those for tones and words,
      similarities and differences were observed for words and tones: Both types of
      stimuli appear to rely on rehearsal mechanisms, but might differ in the involved
      sensorimotor codes.

PMID- 23116414
TI  - The interaction between frontal functioning and encoding processes in reducing
      false memories.
AB  - Studies suggest that age differences in false memories may be related to deficits
      in frontal lobe functioning (FLF; Butler, McDaniel, Dornburg, Price, & Roediger,
      2004, Psychonomic Bulletin & Review, 11, 921). In addition, research has
      demonstrated that item-specific encoding can reduce false memories in younger
      adults ( Arndt & Reder, 2003, Journal of Experimental Psychology: Learning,
      Memory, and Cognition, 28, 830). In the present study we examined whether younger
      and older adults who perform poorly on tests designed to assess frontal function
      would be less likely to benefit from item-specific encoding in a false memory
      paradigm. In three experiments, participants studied categorized word or picture
      lists. Encoding manipulations were designed to emphasize either item-specific or
      relational processing. Younger adults and high FLF older adults showed a
      reduction in false memories when item-specific processing was implemented.
      However, low FLF older adults showed a reduction in false memories only when
      relational processing was impoverished. Results suggest that frontal function
      directly influences the engagement in distinctive encoding processes. 

PMID- 23116415
TI  - Looking at allergens increases symptom report in patients with allergic asthma.
AB  - OBJECTIVE: Accurate symptom perception is highly important for self-management
      and clinical treatment of asthma. Recent findings suggest that psychological
      factors can greatly impact asthma symptom perception. This study examined whether
      looking at allergens would lead to changes in perceived asthma symptoms. METHODS:
      Allergic asthma patients and healthy controls viewed picture series containing
      either allergens or neutral material. Symptom reports and respiratory parameters
      were measured. RESULTS: The present results demonstrate that looking at pictures
      with allergens increases subjective symptom reports in patients with allergic
      asthma in the absence of changes in objective respiratory parameters, but not in
      healthy controls. CONCLUSIONS: The results are suggestive of preceding learning
      processes during which patients have learned the association between visual
      representations of allergens and symptom-inducing effects of real contact with
      these allergens. This impacts asthma symptom perception without changes in
      respiratory status and might influence treatment decisions.

PMID- 23116417
TI  - Silyl-based alkyne-modifying linker for the preparation of C-terminal acetylene
      derivatized protected peptides.
AB  - A novel linker for the synthesis of C-terminal acetylene-functionalized protected
      peptides is described. This SAM1 linker is applied in the manual Fmoc-based solid
      phase peptide synthesis of Leu-enkephalin and in microwave-assisted automated
      synthesis of Maculatin 2.1, an antibacterial peptide that contains 18 amino acid
      residues. For the cleavage, treatment with tetramethylammonium fluoride results
      in protected acetylene-derivatized peptides. Alternatively, a one-pot cleavage
      click procedure affords the protected 1,2,3-triazole conjugate in high yields
      after purification.

PMID- 23116418
TI  - Gastrointestinal stromal tumors (GISTs) express somatostatin receptors and bind
      radiolabeled somatostatin analogs.
AB  - BACKGROUND: Gastrointestinal stromal tumors (GISTs) can be effectively treated
      with tyrosine kinase inhibitors (TKIs). However, some patients with GIST develop
      drug resistance, and alternative treatment strategies are therefore needed. The
      aim of this study was to analyze the expression of somatostatin receptors (SSTR)
      in GIST as a target for peptide receptor-mediated radiotherapy (PRRT). MATERIAL
      AND METHODS: Expression profiling of SSTR1-5 was performed on biopsies from 34
      GISTs (16 gastric tumors, 15 small intestinal tumors, and three rectal tumors).
      SSTR scintigraphy ((111)In-octreotide) and measurement of (111)In activity in
      tumor specimens was performed in seven patients. Uptake and internalization of
      (177)Lu- octreotate was studied in primary cell cultures from two patients.
      RESULTS: Quantitative PCR analysis showed expression of SSTR1 and SSTR2 in the
      majority of tumors, while SSTR3-5 were expressed at low levels.
      Immunohistochemical analysis confirmed the presence of SSTR1 and SSTR2 proteins
      in all GISTs, and SSTR3-5 in a subset of tumors. Diagnostic imaging by SSTR
      scintigraphy, using (111)In-octreotide, demonstrated tumor uptake of (111)In in
      three of six GIST patients. Measurement of (111)In activity in excised tumor
      specimens from five patients gave tumor-to-blood (T/B) activity ratios of between
      eight and 96. Tumor cells in primary culture (gastric and small intestinal GIST)
      specifically bound and internalized (177)Lu when incubated with the therapeutic
      compound (177)Lu-octreotate for 4-48 hours (p < 0.05). CONCLUSION: Peptide
      receptor-mediated radiotherapy via SSTR may provide a novel treatment strategy in
      carefully selected GIST patients with TKI-resistant tumors.

PMID- 23116416
TI  - Function of members of the neuropilin family as essential pleiotropic cell
      surface receptors.
AB  - The neuropilin (Nrp) family consists of essential multifunctional vertebrate cell
      surface receptors. Nrps were initially characterized as receptors for class III
      Semaphorin (Sema3) family members, functioning in axon guidance. Nrps have also
      been shown to be critical for vascular endothelial growth factor-dependent
      angiogenesis. Intriguingly, recent data show that Nrp function in these seemingly
      divergent pathways is critically determined by ligand-mediated cross-talk, which
      underlies Nrp function in both physiological and pathological processes. In
      addition to functioning in these two pathways, Nrps have been shown to
      specifically function in a number of other fundamental signaling pathways as
      well. Multiple general mechanisms have been found to directly contribute to the
      pleiotropic function of Nrp. Here we review critical general features of Nrps
      that function as essential receptors integrating multiple molecular cues into
      diverse cellular signaling.

PMID- 23116420
TI  - Synthesis of soluble graphite and graphene.
AB  - Because of graphene's anticipated applications in electronics and its thermal,
      mechanical, and optical properties, many scientists and engineers are interested
      in this material. Graphene is an isolated layer of the pi-stacked hexagonal
      allotrope of carbon known as graphite. The interlayer cohesive energy of
      graphite, or exfoliation energy, that results from van der Waals attractions over
      the interlayer spacing distance of 3.34 A (61 meV/C atom) is many times weaker
      than the intralayer covalent bonding. Since graphene itself does not occur
      naturally, scientists and engineers are still learning how to isolate and
      manipulate individual layers of graphene. Some researchers have relied on the
      physical separation of the sheets, a process that can sometimes be as simple as
      peeling of sheets from crystalline graphite using Scotch tape. Other researchers
      have taken an ensemble approach, where they exploit the chemical conversion of
      graphite to the individual layers. The typical intermediary state is graphite
      oxide, which is often produced using strong oxidants under acidic conditions.
      Structurally, researchers hypothesize that acidic functional groups functionalize
      the oxidized material at the edges and a network of epoxy groups cover the sp(2)
      bonded carbon network. The exfoliated material formed under these conditions can
      be used to form dispersions that are usually unstable. However, more importantly,
      irreversible defects form in the basal plane during oxidation and remain even
      after reduction of graphite oxide back to graphene-like material.  As part of our
      interest in the dissolution of carbon nanomaterials, we have explored the
      derivatization of graphite following the same procedures that preserve the sp(2)
      bonding and the associated unique physical and electronic properties in the
      chemical processing of single-walled carbon nanotubes. In this Account, we
      describe efficient routes to exfoliate graphite either into graphitic
      nanoparticles or into graphene without resorting to oxidation. Our exfoliation
      process involves the intercalation of lithium into bulk graphite to yield
      graphene sheets reduced by the lithium. We can alkylate the resulting graphite
      salt reductively using solubilizing dodecyl groups. By probe microscopy, we show
      that these groups are attached covalently only at the graphitic edges.

PMID- 23116421
TI  - By-product information can stabilize the reliability of communication.
AB  - Although communication underpins many biological processes, its function and
      basic definition remain contentious. In particular, researchers have debated
      whether information should be an integral part of a definition of communication
      and how it remains reliable. So far the handicap principle, assuming signal costs
      to stabilize reliable communication, has been the predominant paradigm in the
      study of animal communication. The role of by-product information produced by
      mechanisms other than the communicative interaction has been neglected in the
      debate on signal reliability. We argue that by-product information is common and
      that it provides the starting point for ritualization as the process of the
      evolution of communication. Second, by-product information remains unchanged
      during ritualization and enforces reliable communication by restricting the
      options for manipulation and cheating. Third, this perspective changes the focus
      of research on communication from studying signal costs to studying the costs of
      cheating. It can thus explain the reliability of signalling in many communication
      systems that do not rely on handicaps. We emphasize that communication can often
      be informative but that the evolution of communication does not cause the
      evolution of information because by-product information often predates and
      stimulates the evolution of communication. Communication is thus a consequence
      but not a cause of reliability. Communication is the interplay of inadvertent,
      informative traits and evolved traits that increase the stimulation and
      perception of perceivers. Viewing communication as a complex of inadvertent and
      derived traits facilitates understanding of the selective pressures shaping
      communication and those shaping information and its reliability. This viewpoint
      further contributes to resolving the current controversy on the role of
      information in communication.

PMID- 23116422
TI  - Use of routine hospital morbidity data together with weight and height of
      patients to predict  in-hospital complications following total joint replacement.
AB  - BACKGROUND: Routinely collected data such as hospital morbidity data (HMD) are
      increasingly used in studying clinical outcomes among patients undergoing total
      joint replacement (TJR). These data are readily available and cover large
      populations. However, since these data were not originally collected for the
      purpose of health research, a rigorous assessment of their quality is required.
      We assessed the accuracy of the diagnosis of obesity in HMD and evaluated whether
      the augmentation of HMD with actual weight and height of patients could improve
      their ability to predict major in-hospital complications following total joint
      replacement in men. METHODS: The electronic records of 857 participants in the
      Health In Men Study (HIMS) who had had TJR were linked with Western Australia
      HMD. HMD-recorded diagnosis of obesity was validated using the actual weight and
      height obtained from HIMS. In-hospital major complications were modelled using
      multivariable logistic regressions that either included the actual weight and
      height or HMD-recorded obesity. Model discrimination was calculated using area
      under ROC curve. RESULTS: The HMD failed to detect 70% of the obese patients.
      Only 64 patients (7.5%) were recorded in HMD as obese although 216 (25%) were
      obese [BMI: >=30kg/m2] (sensitivity: 0.2, positive predictive value: 0.7).
      Overall, 174 patients (20%) developed an in-hospital major complication which was
      significantly higher in the overweight and obese comparing with patients with
      normal weight. HMD-recorded obesity was not independently associated with major
      complications, whereas a dose-response relationship between weight and these
      complications was observed (P=0.004). Using the actual weight and height of the
      participants instead of HMD-recorded diagnosis of obesity improved model
      discrimination by 9%, with areas under ROC curve of: 0.69, 95% CI: 0.64-0.73 for
      the model with HMD-recorded obesity compared with 0.75, 95% CI: 0.70-0.79 for the
      model with actual weight and height, P<0.001. CONCLUSION: Body weight is an
      important risk factor for in-hospital complications in patients undergoing TJR.
      HMD systems do not include weight and height as variables whose recording is
      mandatory. Augmenting HMD with patients' weight and height may improve prediction
      of major complications following TJR. Our study suggests making these variables
      mandatory in any hospital morbidity data system.

PMID- 23116423
TI  - The devil is in the detail: children's recollection of details about their prior
      experiences.
AB  - Adults sometimes report highly specific details of childhood events, including
      the weather, what they or others were wearing, as well as information about what
      they or others said or were thinking at the time. When these details are reported
      in the course of research they shape our theories of memory development; when
      they are reported in a criminal trial they influence jurors' evaluation of guilt
      or innocence. The key question is whether these details were encoded at the time
      the event took place or have been added after the fact. We addressed this
      question prospectively by examining the memory accounts of children. In
      Experiment 1 we coded the reports of 5- to 6-year-olds and 9- to 10-year-olds who
      had experienced a unique event. We found that spontaneous mentions of these
      specific details were exceedingly rare. In Experiment 2 we questioned additional
      children about a similar event using specific questions to extract those details.
      We found that 9- to 10-year-olds were able to accurately answer, while 5- to 6
      year-olds had considerable difficulty. Moreover, when the younger children did
      respond they provided generic, forensically inadequate, information. These data
      have important implications for the courtroom and for current theories of memory
      development and childhood amnesia.

PMID- 23116424
TI  - Examination of the reactivity of benzoxaboroles and related compounds with a cis
      diol.
AB  - Benzoxaboroles have been emerging as an interesting and useful scaffold in drug
      discovery due to their apparently unique reactivity toward diols under
      physiological conditions. In this work, the reaction of benzoxaborole with the
      diol-containing, fluorescent dye Alizarin Red S is probed. Steady-state and
      presteady-state experiments have been conducted for the characterization of the
      reactions over a wide range of pH. Results indicate that Alizarin Red S reacts
      with both the boronic (neutral, trigonal) form as well as the boronate (anionic,
      tetrahedral) form of benzoxaborole in a reaction largely analogous to that
      previously determined for the simple phenylboronic acid. However, in certain key
      aspects, the reactivity of the benzoxaborole was found to differ from that of
      simple phenylboronic acid. The structural origin of these differences has been
      explored by examination of compounds related to both benzoxaborole and
      phenylboronic acid. These results may be applied to rational drug discovery
      efforts aimed at expanding the use of benzoxaboroles in medicine.

PMID- 23116425
TI  - Guideline on the management of bleeding in patients on antithrombotic agents.

PMID- 23116426
TI  - Continuing education--"the action level"(r).

PMID- 23116427
TI  - Clinical evaluation of the feasibility of minimally invasive surgery in
      esophageal cancer.
AB  - INTRODUCTION: Open thoracotomy laparotomy with extended dissection for esophageal
      cancer is associated with problems such as delayed postoperative recovery and
      decreased quality of life. In contrast, in minimally invasive surgery, these
      problems can be improved. In the present study, we investigated the feasibility
      of minimally invasive surgery in esophageal cancer. METHODS: In this
      retrospective study, we evaluated esophagectomy performed by the same surgeon in
      98 patients with thoracic esophageal cancer. Open surgery was performed in 30
      patients (open group), and minimally invasive surgery was performed in 68
      patients (MIS group). We compared the invasiveness and radical cure of cancer by
      minimally invasive surgery with that of open surgery. RESULTS: Comparison between
      the open and MIS groups showed that intraoperative blood loss, intraoperative and
      postoperative transfused blood volume, and surgical site infection rates were
      significantly lower in the MIS group. The duration of postoperative endotracheal
      intubation and hospital stay were significantly shorter in the MIS group. The
      histopathologic type was squamous cell carcinoma in 93.3% in the open group and
      92.6% in the MIS group. The respective 3-year survival rates were 36.7% and
      71.5%, and the respective 5-year survival rates were 26.7% and 61.5%. CONCLUSION:
      Based on a historical control study at a single institution, we are unable to
      conclude that minimally invasive surgery is superior to open surgery. However,
      our results indicate that minimally invasive surgery is feasible as a surgical
      procedure in esophageal cancer.

PMID- 23116428
TI  - Within-session practice eliminates age differences in cognitive control.
AB  - ABSTRACT Previous research employing short-term practice and long-term training
      have been successful in reducing cognitive control deficits in the elderly. The
      goal of this study was to examine the effect of practice within session on a
      demanding cognitive control task. Nineteen older adults and 16 young adults
      performed 720 trials of a cued version of the Stroop task, in which an
      instructional cue is presented before each individually presented Stroop
      stimulus. Statistical analyses focused on the most difficult color-naming
      condition in task-switching blocks. Overall, participants showed faster reaction
      times and decreased errors with practice, particularly on incongruent trials.
      Older adults showed a greater reduction in errors with practice than young
      adults. Moreover, older adults, but not young adults, showed a reduction in
      errors and reaction times with practice on incongruent trials. Findings further
      suggest that practice reduces age-related differences in cognitive control.
      Improvements in cognitive control functioning has implications for treating
      functional deficits in older adults. 

PMID- 23116429
TI  - Clinical pathways can improve the quality of pain management in home palliative
      care in remote locations: retrospective study on Kozu Island, Japan.
AB  - INTRODUCTION: Recent studies show that a clinical pathway (CP) optimizes pain
      management in palliative care; however, studies on CPs in home palliative care,
      especially in remote locations, are scarce. Physicians performing palliative care
      in remote areas frequently face characteristic difficulties. The CP is an
      effective tool to overcome these difficulties. This study evaluates the
      effectiveness of the CP in home palliative care on a remote island. METHODS: This
      study reviewed 24 patients (17 in a pre-CP group and seven in a post-CP group)
      who received home palliative care on Kozu Island in south-eastern Japan from
      April 2006 to December 2011. To evaluate CP effectiveness, the authors compared
      patients in whom a rescue opioid was set, and nonsteroidal anti- inflammatory
      drugs (NSAIDs), antiemetics, and laxatives drug were used with opioids in the
      post-CP group compared with those in the pre-CP group. To assess pain management
      quality, authors compared Pain Management Index (PMI) scores on day 1 (baseline);
      day 8 following CP initiation; and within 3 days before death. RESULTS: The
      proportion of patients in whom a rescue dose was set was 100% in the post-CP
      group versus 46% in the pre-CP group (<em>p</em>=0.04). The proportion of
      patients in whom NSAIDs were used with opioids was 100% in the post-CP group
      versus 18% in the pre-CP group (<em>p</em>=0.002). The proportion of patients in
      whom antiemetics and laxatives were used with opioids was 100% in the post-CP
      group versus 27% in the pre-CP group (<em>p</em>=0.009). Baseline PMI scores were
      not significantly different between groups (-1 in post-CP group versus 0 in pre
      CP group, <em>p</em>=0.1); however, PMI scores at day 8 and within 3 days before
      death were significantly higher in the post-CP group (1.9 and 2.9) than in the
      pre-CP group (0.2 and -0.4) (<em>p</em>=0.007 and <em>p</em>=0.0005,
      respectively). CONCLUSION: Implementation of a CP for pain management in home
      palliative care in remote locations could improve compliance with the WHO pain
      management guidelines and the quality of pain management.

PMID- 23116430
TI  - Clopidogrel variability: role of plasma protein binding alterations.
AB  - AIM: The large inter-individual variability in clopidogrel response is attributed
      to pharmacokinetics. Although, it has been used since the late 1990s the
      pharmacokinetic fate of clopidogrel and its metabolites are poorly explained. The
      variable response to clopidogrel is believed to be multi-factorial, caused both
      by genetic and non-genetic factors. In this study, we examined whether the
      inactive metabolite can alter the plasma protein binding of the active
      metabolite, thus explaining the large inter-individual variability associated
      with clopidogrel response. METHODS: Female subjects (n = 28) with stable coronary
      disease who were not taking clopidogrel were recruited. Serial blood samples were
      collected following 300 mg oral dose of clopidogrel, plasma was isolated and
      quantified for total and free concentrations of active and inactive metabolites.
      Inhibition of platelet aggregation was measured using the phosphorylated
      vasodilator stimulated phosphoprotein (VASP) assay. RESULTS: A significant
      correlation was observed between VASP and both free (r = 0.49, P < 0.05) and
      total (r = 0.49, P < 0.05) concentrations of the active metabolite. Surprisingly,
      we observed a significant correlation with both free (r = 0.42, P < 0.05) and
      total (r = 0.67, P < 0.001) concentrations of the inactive metabolite as well.
      Free fractions of the active metabolite rose with increasing protein binding of
      the inactive metabolite (P < 0.05). CONCLUSIONS: The above in vivo data suggest
      that the inactive metabolite displaces the active metabolite from binding sites.
      Thus, the inactive metabolite might increase the free concentration of the active
      metabolite leading to enhanced inhibition of platelet aggregation. The plasma
      protein binding mechanism would offer an additional therapeutic strategy to
      optimize clopidogrel pharmacotherapy.

PMID- 23116432
TI  - Structural and functional studies on a 3'-epimerase involved in the biosynthesis
      of dTDP-6-deoxy-D-allose.
AB  - Unusual deoxy sugars are often attached to natural products such as antibiotics,
      antifungals, and chemotherapeutic agents. One such sugar is mycinose, which has
      been found on the antibiotics chalcomycin and tylosin. An intermediate in the
      biosynthesis of mycinose is dTDP-6-deoxy-D-allose. Four enzymes are required for
      the production of dTDP-6-deoxy-D-allose in Streptomyces bikiniensis, a soil
      dwelling microbe first isolated from the Bikini and Rongelap atolls. Here we
      describe a combined structural and functional study of the enzyme ChmJ, which
      reportedly catalyzes the third step in the pathway leading to dTDP-6-deoxy-D
      allose formation. Specifically, it has been proposed that ChmJ is a 3'-epimerase
      that converts dTDP-4-keto-6-deoxyglucose to dTDP-4-keto-6-deoxyallose. This
      activity, however, has never been verified in vitro. As reported here, we
      demonstrate using (1)H nuclear magnetic resonance that ChmJ, indeed, functions as
      a 3'-epimerase. In addition, we determined the structure of ChmJ complexed with
      dTDP-quinovose to 2.0 A resolution. The structure of ChmJ shows that it belongs
      to the well-characterized "cupin" superfamily. Two active site residues, His 60
      and Tyr 130, were subsequently targeted for study via site-directed mutagenesis
      and kinetic analyses, and the three-dimensional architecture of the H60N/Y130F
      mutant protein was determined to 1.6 A resolution. Finally, the structure of the
      apoenzyme was determined to 2.2 A resolution. It has been previously suggested
      that the position of a conserved tyrosine, Tyr 130 in the case of ChmJ,
      determines whether an enzyme in this superfamily functions as a mono- or
      diepimerase. Our results indicate that the orientation of the tyrosine residue in
      ChmJ is a function of the ligand occupying the active site cleft.

PMID- 23116431
TI  - Intravaginal practices and microbicide acceptability in Papua New Guinea:
      implications for HIV prevention in a moderate-prevalence setting.
AB  - BACKGROUND: The acceptability of female-controlled biomedical prevention
      technologies has not been established in Papua New Guinea, the only country in
      the Pacific region experiencing a generalised, moderate-prevalence HIV epidemic.
      Socio-cultural factors likely to impact on future product uptake and
      effectiveness, such as women's ability to negotiate safer sexual choices, and
      intravaginal hygiene and menstrual practices (IVP), remain unclear in this
      setting. METHODS: A mixed-method qualitative study was conducted among women and
      men attending a sexual health clinic in Port Moresby. During in-depth interviews,
      participants used copies of a hand-drawn template to indicate how they wash/clean
      the vulva and/or vagina. Interviewers pre-filled commercially available vaginal
      applicators with 2-3mL KY Jelly(r) to create a surrogate vaginal microbicide
      product, which was demonstrated to study participants. RESULTS: A total of 28
      IDIs were conducted (women=16; men=12). A diverse range of IVP were reported. The
      majority of women described washing the vulva only with soap and water as part of
      their daily routine; in preparation for sex; and following sexual intercourse.
      Several women described cleaning inside the vagina using fingers and soap at
      these same times. Others reported cleaning inside the vagina using a hose
      connected to a tap; using vaginal inserts, such as crushed garlic; customary
      menstrual 'steaming' practices; and the use of material fragments, cloth and
      newspaper to absorb menstrual blood. Unprotected sex during menstruation was
      common. The majority of both women and men said that they would use a vaginal
      microbicide gel for HIV/STI protection, should a safe and effective product
      become available. Microbicide use was considered most appropriate in 'high-risk'
      situations, such as sex with non-regular, transactional or commercial partners.
      Most women felt confident that they would be able to negotiate vaginal
      microbicide use with male sexual partners but if necessary would be prepared to
      use product covertly. CONCLUSIONS: Notional acceptability of a vaginal
      microbicide gel for HIV/STI prevention was high among both women and men. IVP
      were diverse in nature, socio-cultural dimensions and motivators. These factors
      are likely to impact on the future acceptability and uptake of vaginal
      microbicides and other biomedical HIV prevention technologies in this setting.

PMID- 23116433
TI  - MAOA promoter methylation and susceptibility to carotid atherosclerosis: role of
      familial factors in a monozygotic twin sample.
AB  - BACKGROUND: Atherosclerosis is a complex process involving both genetic and
      epigenetic factors. The monoamine oxidase A (MAOA) gene regulates the metabolism
      of key neurotransmitters and has been associated with cardiovascular risk
      factors. This study investigates whether MAOA promoter methylation is associated
      with atherosclerosis, and whether this association is confounded by familial
      factors in a monozygotic (MZ) twin sample. METHODS: We studied 84 monozygotic
      (MZ) twin pairs drawn from the Vietnam Era Twin Registry. Carotid intima-media
      thickness (IMT) was measured by ultrasound. DNA methylation in the MAOA promoter
      region was quantified by bisulfite pyrosequencing using genomic DNA isolated from
      peripheral blood leukocytes. The association between DNA methylation and IMT was
      first examined by generalized estimating equation, followed by matched pair
      analyses to determine whether the association was confounded by familial factors.
      RESULTS: When twins were analyzed as individuals, increased methylation level was
      associated with decreased IMT at four of the seven studied CpG sites. However,
      this association substantially reduced in the matched pair analyses. Further
      adjustment for MAOA genotype also considerably attenuated this association.
      CONCLUSIONS: The association between MAOA promoter methylation and carotid IMT is
      largely explained by familial factors shared by the twins. Because twins reared
      together share early life experience, which may leave a long-lasting epigenetic
      mark, aberrant MAOA methylation may represent an early biomarker for unhealthy
      familial environment. Clarification of familial factors associated with DNA
      methylation and early atherosclerosis will provide important information to
      uncover clinical correlates of disease.

PMID- 23116435
TI  - New allelic variants found in key rice salt-tolerance genes: an association
      study.
AB  - Salt stress is a complex physiological trait affecting plants by limiting growth
      and productivity. Rice, one of the most important food crops, is rated as salt
      sensitive. High-throughput screening methods are required to exploit novel
      sources of genetic variation in rice and further improve salinity tolerance in
      breeding programmes. To search for genotypic differences related to salt stress,
      we genotyped 392 rice accessions by EcoTILLING. We targeted five key salt-related
      genes involved in mechanisms such as Na(+) /K(+)  ratio equilibrium, signalling
      cascade and stress protection, and we found 40 new allelic variants in coding
      sequences. By performing association analyses using both general and mixed linear
      models, we identified 11 significant SNPs related to salinity. We further
      evaluated the putative consequences of these SNPs at the protein level using
      bioinformatic tools. Amongst the five nonsynonymous SNPs significantly associated
      with salt-stress traits, we found a T67K mutation that may cause the
      destabilization of one transmembrane domain in OsHKT1;5, and a P140A alteration
      that significantly increases the probability of OsHKT1;5 phosphorylation. The
      K24E mutation can putatively affect SalT interaction with other proteins thus
      impacting its function. Our results have uncovered allelic variants affecting
      salinity tolerance that may be important in breeding.

PMID- 23116436
TI  - Intraoperative findings and procedures in culturally and geographically different
      patient and surgeon populations: an anterior cruciate ligament reconstruction
      registry comparison between Norway and the USA.
AB  - BACKGROUND AND PURPOSE: Patient and implant registries are important clinical
      tools in monitoring and benchmarking quality of care. For comparisons amongst
      registries to be valid, a common data set with comparable definitions is
      necessary. In this study we compared the patients in the Norwegian Knee Ligament
      Registry (NKLR) and the Kaiser Permanente Anterior Cruciate Ligament
      Reconstruction Registry (KP ACLRR) with regard to intraarticular findings,
      procedures, and graft fixation characteristics reported by the operating surgeon
      for both primary and revision anterior cruciate ligament reconstructions (ACLRs).
      METHODS: We performed a cross-sectional comparison of the NKLR and KP ACLRR
      cohorts registered between 2005 and 2010. Aggregate-level data including patient
      characteristics (age, sex, and laterality), meniscal and cartilage injury
      patterns and corresponding treatment procedures, choice of graft, and fixation
      characteristics (type and component material) were shared between registries.
      Descriptive analyses were then conducted. RESULTS: During the study period,
      11,217 ACLRs were registered in the NKLR and 11,050 were registered in the KP
      ACLRR. In the NKLR, hamstring autograft was used more (68% vs. 30%) for primary
      ACLRs and allograft was used less (0.2% vs. 41%) than in the KP ACLRR. The KP
      ACLRR reports more meniscal tears among both primary and revision ACLRs (63% and
      50% vs. 49% and 36%). The NKLR reports less use of biodegradable fixation
      devices. CONCLUSIONS: Baseline findings between the NKLR and the KP ACLRR were
      congruent regarding patient characteristics and most injury patterns, adding to
      the evidence that comparisons and collaborations between these registries will
      provide generalizable information to the international orthopedic community. The
      variation in the treatment, including graft and implant selection and meniscus
      procedures, between the 2 registries provides opportunities to explore the impact
      of treatment choices on the outcomes of ACLRs.

PMID- 23116437
TI  - Reverse hybrid and cemented hip replacement compared using radiostereometry and
      dual-energy X-ray absorptiometry: 43 hips followed for 2 years in a prospective
      trial.
AB  - BACKGROUND AND PURPOSE: Total hip replacement (THR) with a reverse hybrid (RH), a
      combination of a cemented polyethylene cup and a cementless femoral stem, has
      been increasingly used in Scandinavia. In a randomized trial, we compared an RH
      THR with a proximal hydroxyapatite- (HA-) coated stem to a conventional cemented
      THR. Both groups received the same polyethylene cup. PATIENTS AND METHODS: 51
      patients (52 hips) were included. Radiostereometry (RSA) and dual-energy X-ray
      absorptiometry (DEXA) were performed postoperatively and after 6, 12, and 24
      months. 42 patients (43 hips) were followed for 2 years. RESULTS: Mean cup
      rotation around the x-axis was 0.13 degrees  for the cemented group and -0.24
      degrees  for the RH group (p = 0.03). Cup migration in the other axes, and stem
      migration and wear were similar between the 2 study groups. Bone remodeling
      around the cup was also similar between the groups. Bone loss in Gruen zone 1 was
      18% for the cementless stems, as compared to an increase of 1.4% for the cemented
      ones (p < 0.001). Bone loss was similar in the other Gruen zones. Harris hip
      score and Oxford hip score were similar pre- and postoperatively in the 2 groups.
      INTERPRETATION: In the present study, RH THR with a cementless hydroxyapatite
      coated stem and conventional cemented THR did not show any major differences
      regarding stem migration and bone loss after 2 years of follow-up.

PMID- 23116438
TI  - 10-year results of a new low-monomer cement: follow-up of a randomized RSA study.
AB  - BACKGROUND AND PURPOSE: The properties and performance of a new low-monomer
      cement were examined in this prospective randomized, controlled RSA study. 5-year
      data have already been published, showing no statistically significant
      differences compared to controls. In the present paper we present the 10-year
      results. METHODS: 44 patients were originally randomized to receive total hip
      replacement with a Lubinus SPII titanium-aluminum-vanadium stem cemented either
      with the new Cemex Rx bone cement or with control bone cement, Palacos R.
      Patients were examined using RSA, Harris hip score, and conventional radiographs.
      RESULTS: At 10 years, 33 hips could be evaluated clinically and 30 hips could be
      evaluated with RSA (16 Cemex and 14 Palacos). 9 patients had died and 4 patients
      were too old or infirm to be investigated. Except for 1 hip that was revised for
      infection after less than 5 years, no further hips were revised before the 10
      year follow-up. There were no statistically significant clinical differences
      between the groups. The Cemex cement had magnitudes of migration similar to or
      sometimes lower than those of Palacos cement. In both groups, most hips showed
      extensive radiolucent lines, probably due to the use of titanium alloy stems.
      INTERPRETATION: At 10 years, the Cemex bone cement tested performed just as well
      as the control (Palacos bone cement).

PMID- 23116439
TI  - Dual-mobility cups for revision due to instability are associated with a low rate
      of re-revisions due to dislocation: 228 patients from the Swedish Hip
      Arthroplasty Register.
AB  - BACKGROUND AND PURPOSE: Revision total hip arthroplasty (THA) due to recurrent
      dislocations is associated with a high risk of persistent instability. We
      hypothesized that the use of dual-mobility cups would reduce the risk of re
      revision due to dislocation after revision THA. PATIENTS AND METHODS: 228 THA cup
      revisions (in 228 patients) performed due to recurrent dislocations and employing
      a specific dual-mobility cup (Avantage) were identified in the Swedish Hip
      Arthroplasty Register. Kaplan-Meier survival analysis was performed with re
      revision due to dislocation as the primary endpoint and re-revision for any
      reason as the secondary endpoint. Cox regression models were fitted in order to
      calculate the influence of various covariates on the risk of re-revision.
      RESULTS: 58 patients (25%) had been revised at least once prior to the index cup
      revision. The surgical approach at the index cup revision was lateral in 99 cases
      (44%) and posterior in 124 cases (56%). Median follow-up was 2 (0-6) years after
      the index cup revision, and by then 18 patients (8%) had been re-revised for any
      reason. Of these, 4 patients (2%) had been re-revised due to dislocation.
      Survival after 2 years with the endpoint revision of any component due to
      dislocation was 99% (95% CI: 97-100), and it was 93% (CI: 90-97) with the
      endpoint revision of any component for any reason. Risk factors for subsequent re
      revision for any reason were age between 50-59 years at the time of the index cup
      revision (risk ratio (RR) = 5 when compared with age > 75, CI: 1-23) and previous
      revision surgery to the relevant joint (RR = 1.7 per previous revision, CI: 1-3).
      INTERPRETATION: The risk of re-revision due to dislocation after insertion of
      dual-mobility cups during revision THA performed for recurrent dislocations
      appears to be low in the short term. Since most dislocations occur early after
      revision THA, we believe that this device adequately addresses the problem of
      recurrent instability. Younger age and prior hip revision surgery are risk
      factors for further revision surgery. However, problems such as potentially
      increased liner wear and subsequent aseptic loosening may be associated with the
      use of such devices in the long term.

PMID- 23116440
TI  - The type of surgical approach influences the risk of revision in total hip
      arthroplasty: a study from the Swedish Hip Arthroplasty Register of 90,662 total
      hipreplacements with 3 different cemented prostheses.
AB  - BACKGROUND AND PURPOSE: The most common surgical approaches in total hip
      arthroplasty in Sweden are the posterior and the anterolateral transgluteal
      approach. Currently, however, there is insufficient evidence to prefer one over
      the other regarding risk of subsequent surgery. PATIENTS AND METHODS: We searched
      the Swedish Hip Arthroplasty Register between the years 1992 and 2009 to compare
      the posterior and anterolateral transgluteal approach regarding risk of revision
      in the 3 most common all-cemented hip prosthesis designs in Sweden. 90,662 total
      hip replacements met the inclusion criteria. We used Cox regression analysis for
      estimation of prosthesis survival and relative risk of revision due to
      dislocation, infection, or aseptic loosening. RESULTS: Our results show that for
      the Lubinus SPII prosthesis and the Spectron EF Primary prosthesis, the
      anterolateral transgluteal approach gave an increased risk of revision due to
      aseptic loosening (relative risk (RR) = 1.3, 95% CI: 1.0-1.6 and RR = 1.6, CI:
      1.0-2.5) but a reduced risk of revision due to dislocation (RR = 0.7, CI: 0.5-0.8
      and RR = 0.3, CI: 0.1-0.4). For the Exeter Polished prosthesis, the surgical
      approach did not affect the outcome for dislocation or aseptic loosening. The
      surgical approach had no influence on the risk of revision due to infection in
      any of these designs. INTERPRETATION: This observational study shows that the
      surgical approach affected the risk of revision due to aseptic loosening and
      dislocation for 2 of the most commonly used cemented implants in Sweden. Further
      studies are needed to determine whether these results are generalizable to other
      implants and to uncemented fixation.

PMID- 23116441
TI  - The polymorphic nature of membrane-active peptides from biophysical and
      structural investigations.
AB  - Membrane-active peptides exhibit a wide variety of biological functions including
      pore formation, signaling and antimicrobial activities. They are also capable of
      transporting large cargo such as proteins or nucleic acids across cell membranes.
      This review summarizes biophysical and structural investigations on hydrophobic,
      amphipathic and heavily charged peptides that reveal a very dynamic view on their
      membrane interactions. Individual peptides are able to adopt a variety of
      different conformations and topology and at the same time exhibit multimodal
      functionalities. Examples discussed in this paper include peptaibols, magainins,
      cell penetrating peptides and designed histidine-rich sequences with potent
      antimicrobial and nucleic acid transfection activities.

PMID- 23116442
TI  - Antimicrobial peptide rBPI21: a translational overview from bench to clinical
      studies.
AB  - Gram-negative bacteria infection is sometimes followed by septic shock. This
      serious health condition is caused by the segregation of the lipopolysaccharide
      (LPS) from bacterial membrane into the bloodstream. Due to bacterial resistance,
      new antibiotics are needed. Most of the active antibiotics possess bactericidal
      effect, but lack LPS neutralization properties to prevent or neutralize septic
      shock. Antimicrobial peptides are a new class of antibiotics not prone to
      bacterial resistance, because their main target is the membrane. It is difficult
      for bacteria to critically change their membrane composition without affecting
      its molecular processes. rBPI21 is a recombinant antimicrobial peptide developed
      from an antimicrobial protein produced in neutrophils, the
      bactericidal/permeability-increasing protein (BPI) that ended phase III clinical
      trials against meningitis with success, reducing serious complications, such as
      amputations. It interacts preferentially with LPS with high affinity and at the
      same time has bactericidal effect. Here, we gather evidence that the interaction
      of the rBPI21 with LPS is mainly electrostatic, first, followed by massive LPS
      aggregation, which is correlated with its clearance from the bloodstream. The
      molecular mechanism at membrane level includes the peptide interactions with
      negatively charged phospholipids that promote outer and inner membrane
      hemi(fusion). This perturbation is followed by membrane permeabilization.

PMID- 23116443
TI  - Membrane interacting peptides: from killers to helpers.
AB  - Membrane interacting peptides are reviewed in terms of structure and mode of
      action on lipid membranes. Helical, beta-stranded, peptides containing both
      helices and strands, cyclic, lipopeptides and short linear peptides are seen to
      considerably modulate membrane function. Among peptides that lead to membrane
      alteration or permeation, antimicrobial peptides play an important role and some
      of them may be foreseen as potential new antibiotics. Alternatively, peptides
      that do not destroy the membrane are also very important in modulating the
      structure and dynamics of the lipid bilayer and play important roles in membrane
      protein functions. Peptide lipid complexes are shown to be very variable in
      structure and dynamics: "carpet", "barrel stave", toroid and disordered pores,
      electrostatic wedge and molecular electroporation models are discussed. Their
      assembly is reviewed in terms of electric, amphipathic and dynamic properties of
      both lipids and peptides.

PMID- 23116444
TI  - Zinc-induced cardiomyocyte relaxation in a rat model of hyperglycemia is
      independent of myosin isoform.
AB  - It has been reported previously that diabetic cardiomyopathy can be inhibited or
      reverted with chronic zinc supplementation. In the current study, we hypothesized
      that total cardiac calcium and zinc content is altered in early onset diabetes
      mellitus characterized in part as hyperglycemia (HG) and that exposure of zinc
      ion (Zn2+) to isolated cardiomyocytes would enhance contraction-relaxation
      function in HG more so than in nonHG controls. To better control for differential
      cardiac myosin isoform expression as occurs in rodents after beta-islet cell
      necrosis, hypothyroidism was induced in 16 rats resulting in 100% beta-myosin
      heavy chain expression in the heart. beta-Islet cell necrosis was induced in half
      of the rats by streptozocin administration. After 6 wks of HG, both HG and nonHG
      controls rats demonstrated similar myofilament performance measured as thin
      filament calcium sensitivity, native thin filament velocity in the myosin
      motility assay and contractile velocity and power. Extracellular Zn2+ reduced
      cardiomyocyte contractile function in both groups, but enhanced relaxation
      function significantly in the HG group compared to controls. Most notably, a
      reduction in diastolic sarcomere length with increasing pacing frequencies, i.e.,
      incomplete relaxation, was more pronounced in the HG compared to controls, but
      was normalized with extracellular Zn2+ application. This is a novel finding
      implicating that the detrimental effect of HG on cardiomyocyte Ca2+ regulation
      can be amelioration by Zn2+. Among the many post-translational modifications
      examined, only phosphorylation of ryanodine receptor (RyR) at S-2808 was
      significantly higher in HG compared to nonHG. We did not find in our hypothyroid
      rats any differentiating effects of HG on myofibrillar protein phosphorylation,
      lysine acetylation, O-linked N-acetylglucosamine and advanced glycated end
      products, which are often implicated as complicating factors in cardiac
      performance due to HG. Our results suggest that the relaxing effects of Zn2+ on
      cardiomyocyte function are more pronounced in the HG state due an insulin
      dependent effect of enhancing removal of cytosolic Ca2+ via SERCA2a or NCX or by
      reducing Ca2+ influx via L-type channel or Ca2+ leak through the RyR.
      Investigations into the effects of Zn2+ on these mechanisms are now underway.

PMID- 23116445
TI  - Stability of cyclic imine toxins: interconversion of pinnatoxin amino ketone and
      pinnatoxin A in aqueous media.
AB  - Pinnatoxins belong to the cyclic imine (CI) group of marine toxins with a unique
      toxicological profile. The need for structural integrity of the aliphatic 7
      membered cyclic imine for the potent bioactivity of pinnatoxins has been
      experimentally demonstrated. In this study, we probe interconversion of the
      natural cyclic imine and its open form, pinnatoxin A amino ketone (PnTX AK),
      under physiologically relevant aqueous conditions. Our studies demonstrate the
      high stability of PnTX A. The unusual stability of the imine ring in PnTX A has
      implications for its oral toxicity and detoxification. These studies, as well the
      access to PnTX amino ketone, were enabled by the total synthesis of (+)
      pinnatoxin A completed previously in our laboratory.

PMID- 23116446
TI  - Cleavage of IgG1 in gingival crevicular fluid is associated with the presence of
      Porphyromonas gingivalis.
AB  - BACKGROUND AND OBJECTIVES: Immunoglobulin (Ig) G1 plays an important role in the
      adaptive immune response. Kgp, a lysine-specific cysteine protease from
      Porphyromonas gingivalis, specifically hydrolyses IgG1 heavy chains. The purpose
      of this study was to examine whether cleavage of IgG1 occurs in gingival
      crevicular fluid (GCF) in vivo, and whether there is any association with the
      presence of Porphyromonas gingivalis and other periodontopathogens. MATERIAL AND
      METHODS: GCF was obtained from nine patients with aggressive periodontitis, nine
      with chronic periodontitis and five periodontally healthy individuals. The
      bacterial loads of Porphyromonas gingivalis, Aggregatibacter
      actinomycetemcomitans, Treponema denticola, Prevotella intermedia and Tannerella
      forsythia were analysed by real-time polymerase chain reaction, and the presence
      and cleavage of IgG1 and IgG2 were determined using Western blotting. Kgp levels
      were measured by ELISA. RESULTS: Cleaved IgG1 was identified in the GCF from 67%
      of patients with aggressive periodontitis and in 44% of patients with chronic
      periodontitis. By contrast, no cleaved IgG1 was detectable in healthy controls.
      No degradation of IgG2 was detected in any of the samples, regardless of health
      status. Porphyromonas gingivalis was found in high numbers in all samples in
      which cleavage of IgG1 was detected (P < 0.001 compared with samples with no IgG
      cleavage). Furthermore, high numbers of Tannerella forsythia and Prevotella
      intermedia were also present in these samples. The level of Kgp in the GCF
      correlated with the load of Porphyromonas gingivalis (r = 0.425, P < 0.01). The
      presence of Kgp (range 0.07-10.98 ng/mL) was associated with proteolytic
      fragments of IgG1 (P < 0.001). However, cleaved IgG1 was also detected in samples
      with no detectable Kgp. CONCLUSION: In patients with periodontitis, cleavage of
      IgG1 occurs in vivo and may suppress antibody-dependent antibacterial activity in
      subgingival biofilms especially those colonized by Porphyromonas gingivalis.

PMID- 23116447
TI  - Retrieval-induced forgetting of words with negative emotionality.
AB  - Retrieval of a memory can cause forgetting of other related memories. This
      phenomenon is known as retrieval-induced forgetting (RIF). Previous studies have
      shown the results with respect to RIF of negative words were mixed, suggesting
      that it should be reconsidered. We used a stem-cued recall test to re-examine
      whether RIF occurs for negative words. A total of 30 undergraduate university
      students (11 male, 19 female) aged 19-22 years (M = 19.83, SD = 0.75) learned
      target words with neutral and negative emotionality. They then engaged in
      retrieval practice for half of the neutral and half of the negative targets by
      completing a word-fragment recall test. Finally a stem-cued recall test
      encompassing all studied targets was administered. The results of this test
      revealed that retrieval practice of neutral words caused forgetting of
      unpractised neutral words, but retrieval practice of negative words did not
      induce forgetting of unpractised negative words. We attribute the absence of RIF
      for negative words to baseline deflation or to integration, which were both
      generated by the inter-relationships between negative words. Further study is
      needed to clarify which factor, baseline deflation or integration, mainly
      influences the lack of RIF of negative words.

PMID- 23116448
TI  - Covalent functionalization of graphene with reactive intermediates.
AB  - Graphene, a material made exclusively of sp(2) carbon atoms with its pi electrons
      delocalized over the entire 2D network, is somewhat chemically inert. Covalent
      functionalization can enhance graphene's properties including opening its band
      gap, tuning conductivity, and improving solubility and stability. Covalent
      functionalization of pristine graphene typically requires reactive species that
      can form covalent adducts with the sp(2) carbon structures in graphene. In this
      Account, we describe graphene functionalization reactions using reactive
      intermediates of radicals, nitrenes, carbenes, and arynes. These reactive species
      covalently modify graphene through free radical addition, CH insertion, or
      cycloaddition reactions. Free radical additions are among the most common
      reaction, and these radicals can be generated from diazonium salts and benzoyl
      peroxide. Electron transfer from graphene to aryl diazonium ion or
      photoactivation of benzoyl peroxide yields aryl radicals that subsequently add to
      graphene to form covalent adducts. Nitrenes, electron-deficient species generated
      by thermal or photochemical activation of organic azides, can functionalize
      graphene very efficiently. Because perfluorophenyl nitrenes show enhanced
      bimolecular reactions compared with alkyl or phenyl nitrenes, perfluorophenyl
      azides are especially effective. Carbenes are used less frequently than nitrenes,
      but they undergo CH insertion and C?C cycloaddition reactions with graphene. In
      addition, arynes can serve as a dienophile in a Diels-Alder type reaction with
      graphene. Further study is needed to understand and exploit the chemistry of
      graphene. The generation of highly reactive intermediates in these reactions
      leads to side products that complicate the product composition and analysis.
      Fundamental questions remain about the reactivity and regioselectivity of
      graphene. The differences in the basal plane and the undercoordinated edges of
      graphene and the zigzag versus arm-chair configurations warrant comprehensive
      studies. The availability of well-defined pristine graphene starting materials in
      large quantities remains a key obstacle to the advancement of synthetic graphene
      chemistry.

PMID- 23116449
TI  - Local regulation of L-type Ca2+ channel sparklets in arterial smooth muscle.
AB  - This review addresses the latest advances in our understanding of the regulation
      of a novel Ca2+ signal called L-type Ca2+ channel sparklets in arterial smooth
      muscle. L-type Ca2+ channel sparklets are elementary Ca2+ influx events produced
      by the opening of a single or a small cluster of L-type Ca2+ channels. These Ca2+
      signals were first visualized in the vasculature in arterial smooth muscle cells.
      In these cells, L-type Ca2+ channel sparklets display two functionally distinct
      gating modalities that regulate local and global [Ca2+](i). The activity of L
      type Ca2+ channel sparklets varies regionally within a cell depending on the
      dynamic activity of a cohort of protein kinases and phosphatases recruited to L
      type Ca2+ channels in the arterial smooth muscle sarcolemma in a complex
      coordinated by the scaffolding molecule AKAP150. We also described a mechanism
      whereby clusters of L-type Ca2+ channels gate cooperatively to amplify
      intracellular Ca2+ signals with likely pathological consequences.

PMID- 23116450
TI  - Estrogen mimetic 4-tert-octylphenol enhances IgE-mediated degranulation of RBL
      2H3 mast cells.
AB  - Allergic diseases such as asthma have been on the rise in recent decades.
      Environmental or occupational exposure to estrogenic synthetic chemicals is
      suspected to be a contributing factor, and previous experimental studies
      indicated that estradiol and some xenoestrogens increase allergic signaling
      responses, such as degranulation, in immune cells. In the current study, data
      showed that the estrogen mimetic 4-tert-octylphenol (4tOP) enhances
      immunoglobulin (Ig) E-mediated degranulation of mammalian mast cell line RBL-2H3
      (RBL). At the noncytotoxic concentrations 10-20 MUM, 4tOP significantly increased
      degranulation in antigen (Ag)-activated RBLs but exerted no marked effect on
      spontaneous levels. Our data suggest that the industrial chemical 4tOP has the
      potential to enhance allergic disease in individuals who are exposed.

PMID- 23116451
TI  - Chronic obstructive pulmonary disease patients have greater systemic
      responsiveness to ex vivo stimulation with swine dust extract and its components
      versus healthy volunteers.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by an airway and
      systemic inflammatory response. Bioaerosols/organic dusts are important
      agricultural pollutants that may lead to COPD. These environments are complex,
      containing a rich source of various microbial components. The objective of this
      study was to determine whether individuals with COPD have enhanced systemic
      responsiveness to settled swine facility organic dust extract (ODE) or its main
      pathogenic components (peptidoglycan [PGN], lipopolysaccharide [LPS]) versus
      healthy volunteers. A modified whole blood assay (WBA) that included occupational
      levels of ODE and concentrations of LPS and PGN found in ODE was used to
      determine systemic responsiveness (mediator release), and sputum inflammatory
      markers were measured to explore for systemic and airway associations. Sputum
      samples were evaluated for cell counts, and tumor necrosis factor (TNF)-alpha,
      interleukin (IL)-8/CXCL8, IL-6, and IL-10. Ex vivo whole blood stimulation with
      ODE, LPS, and PGN each resulted in significant mediator release in all subjects,
      with the highest occurring with ODE; PGN resulted in significantly enhanced TNF
      alpha and IL-8 as compared to LPS. COPD subjects demonstrated greater systemic
      responsiveness using the modified WBA versus healthy controls. Within COPD
      subjects, blood baseline TNF-alpha, IL-8, and IL-10 and ODE-, PGN-, and LPS
      stimulated IL-8 levels significantly correlated with lung function. In
      conclusion, dust-induced mediator release was robust, and PGN, in part, resembled
      dust-induced mediator release. Subjects with COPD demonstrated increased mediator
      release following ex vivo whole blood stimulation with bioaerosol components,
      suggesting that circulating blood cells in COPD subjects may be primed to respond
      greater to microbial/inflammatory insult.

PMID- 23116452
TI  - The impact of intratracheally instilled carbon black on the cardiovascular system
      of rats: elevation of blood homocysteine and hyperactivity of platelets.
AB  - Carbon black (CB) is an industrial chemical with high potential for human
      exposure. Although the relationship between exposure to particulate matter (PM)
      and cardiovascular disease is well documented, the risk of adverse cardiovascular
      effects attributed to CB particles has not been clearly characterized. This study
      was performed to (1) investigate the effects of CB on cardiovascular system and
      (2) identify the target tissue or potential biomarkers. Carbon black with a
      distinct particle size, N330 (ultrafine particle) and N990 (fine particle), was
      intratracheally instilled into rats at a doses of 1, 3, or 10 mg/kg. Measurements
      of thrombotic activity and determination of plasma homocysteine levels, cardiac
      functionality, and inflammatory responses were conducted at 24-h and 1-wk time
      points. Exposure to N330 accelerated platelet-dependent blood clotting at 10
      mg/kg, the highest exposure tested. Unexpectedly, both N330 and N990 led to
      prolongation of activated partial thromboplastin time (aPTT), whereas these CB
      particles failed to affect prothrombin time (PT). N990 produced a significant
      elevation in the level of plasma homocysteine, a well-established etiological
      factor in cardiovascular diseases. Both N330 and N990 induced apparent
      inflammation in the lungs; however, both particles failed to initiate systemic
      inflammation. Neither CB particle produced observable cardiac symptoms as
      detected by electrocardiography. Taken together, data show CB exposure enhanced
      the cardiovascular risk by inducing hyperhomocysteinemia and platelet
      hyperactivity, although these effects may be variable depending on particle size
      and exposure duration. Homocysteine may be a potential biomarker for
      cardiovascular toxicity following CB exposure.

PMID- 23116453
TI  - Age-specific absolute and relative organ weight distributions for Fischer 344
      rats.
AB  - The Fischer 344 (F344) rat has been the standard rat strain used in toxicology
      studies conducted by the National Cancer Institute (NCI) and the National
      Toxicology Program (NTP). However, the numerous reports published to date on
      growth, survival, and tumor incidence have not included an overall compilation of
      organ weight data. Notably, dose-related organ weight effects are endpoints used
      by regulatory agencies to develop toxicity reference values (TRVs) for use in
      human health risk assessments. In addition, physiologically-based pharmacokinetic
      (PBPK) models, which utilize relative organ weights, are increasingly being used
      to develop TRVs. Because a compilation of organ weights for F344 rats could prove
      beneficial for TRV development and PBPK modeling, all available absolute and
      relative organ weight data for untreated control F344 rats were collected from
      NCI/NTP feed, drinking-water, and inhalation studies in order to develop age
      specific distributions. Results showed that organ weights were collected more
      frequently at 2-wk (59 studies), 3-mo (148 studies), and 15-mo (38 studies)
      intervals than at other intervals and more frequently from feeding and inhalation
      than from drinking-water studies. Liver, right kidney, lung, heart, thymus, and
      brain weights were most frequently collected. From the collected data, the mean
      and standard deviation for absolute and relative organ weights were calculated.
      Findings showed age-related increases in absolute weights and decreases in
      relative weights for brain, liver, right kidney, lung, heart, thyroid, and right
      testis. The results suggest a general variability trend in absolute organ weights
      of brain < right testis < heart < right kidney < liver < lung < thymus < thyroid.

PMID- 23116455
TI  - All-optical logic gates based on nanoscale plasmonic slot waveguides.
AB  - We report realizations of nanoscale integrated all-optical XNOR, XOR, NOT, and OR
      logic gates using plasmonic slot waveguides based on linear interference between
      surface plasmon polariton modes. The miniature device size with lateral
      dimensions smaller than 5 MUm, precisely controlled optical phase difference, and
      quasi-monochromatic surface plasmon polariton modes excited by a continuous wave
      830 nm laser beam ensure a high intensity contrast ratio of 24 dB between the
      output logic states "1" and "0". Compared with previous reported results, the
      intensity contrast ratio is enhanced 4-fold, whereas the lateral dimension is
      reduced 4-fold. These compact logic devices are stable, robust, free from
      environmental impact, and much suitable for practical on-chip applications. These
      also provide a means to construct all-optical logic devices and nanophotonic
      processors.

PMID- 23116454
TI  - Expression of CD25 independently predicts early treatment failure of acute
      myeloid leukaemia (AML).

PMID- 23116456
TI  - The influence of aging on attentional refreshing and articulatory rehearsal
      during working memory on later episodic memory performance.
AB  - We investigated age-related changes in two proposed mechanisms of maintenance in
      working memory, articulatory rehearsal, and attentional refreshing, by examining
      the consequences of manipulating the opportunity for each on delayed recall. Both
      experiments utilized modified operation span tasks to vary the opportunity for
      articulatory rehearsal (Experiment 1) and attentional refreshing opportunities
      (Experiment 2). In both experiments, episodic memory was tested for items that
      had been initially studied during the respective operation span task. Older
      adults' episodic memory benefited less from opportunities for refreshing than
      younger adults. In contrast, articulatory rehearsal opportunities did not
      influence episodic memory for either age group. The results suggest that
      attentional refreshing, and not articulatory rehearsal, is important during
      working memory in order to bind more accessible traces at later tests, which
      appears to be more deficient in older adults than younger adults. 

PMID- 23116457
TI  - The interpretation of disease phenotypes to identify TSE strains following murine
      bioassay: characterisation of classical scrapie.
AB  - Mouse bioassay can be readily employed for strain typing of naturally occurring
      transmissible spongiform encephalopathy cases. Classical scrapie strains have
      been characterised historically based on the established methodology of assessing
      incubation period of disease and the distribution of disease-specific vacuolation
      across the brain following strain stabilisation in a given mouse line. More
      recent research has shown that additional methods could be used to characterise
      strains and thereby expand the definition of strain "phenotype". Here we present
      the phenotypic characteristics of classical scrapie strains isolated from 24 UK
      ovine field cases through the wild-type mouse bioassay. PrPSc
      immunohistochemistry (IHC), paraffin embedded tissue blots (PET-blot) and Western
      blotting approaches were used to determine the neuroanatomical distribution and
      molecular profile of PrPSc associated with each strain, in conjunction with
      traditional methodologies. Results revealed three strains isolated through each
      mouse line, including a previously unidentified strain. Moreover IHC and PET-blot
      methodologies were effective in characterising the strain-associated types and
      neuroanatomical locations of PrPSc. The use of Western blotting as a parameter to
      define classical scrapie strains was limited. These data provide a comprehensive
      description of classical scrapie strain phenotypes on isolation through the mouse
      bioassay that can provide a reference for further scrapie strain identification.

PMID- 23116458
TI  - A randomized phase I study of methanesulfonyl fluoride, an irreversible
      cholinesterase inhibitor, for the treatment of Alzheimer's disease.
AB  - AIMS: To ascertain the tolerability profile of single and repeated oral doses of
      methanesulfonyl fluoride (MSF, SNX-001) in healthy aged subjects, and to
      determine the degree of erythrocyte acetylcholinesterase (AChE) inhibition
      induced by MSF after single and repeated oral doses. METHODS: To calculate
      properly the kinetics and the duration of AChE inhibition, the effects of MSF
      were also studied in rodents. These experiments suggested that MSF administered
      three times per week should provide safe and efficacious AChE inhibition. In a
      randomized placebo-controlled phase I study, 3.6 mg, 7.2 mg or 10.8 mg MSF were
      then orally administered to 27 consenting healthy volunteers (aged 50 to 72
      years). After a single dose phase and a 1 week wash-out period, the subjects
      received the same doses three times per week for 2 weeks. RESULTS: Twenty-two out
      of the 27 subjects completed the study. Four patients withdrew due to adverse
      events (AEs) and one for non-compliance. Erythrocyte AChE was inhibited by a
      total of 33%, 46%, and 62% after 2 weeks of 3.6 mg, 7.2 mg and 10.8 mg MSF,
      respectively. No serious AEs occurred. The most frequent AEs were headache (27%),
      nausea (11%) and diarrhoea (8%). CONCLUSIONS: MSF proved to be well tolerated
      even with repeated oral dosing. It is estimated that MSF provided a degree of
      AChE inhibition that should effectively enhance memory. This molecule deserves to
      be tested for efficacy in a pilot randomized controlled study in patients with
      Alzheimer's disease.

PMID- 23116459
TI  - Evaluation of a high-throughput screening method for the detection of the
      excipient-mediated precipitation inhibition of poorly soluble drugs.
AB  - The objective of the present study was to develop and evaluate a high-throughput
      (HT) precipitation inhibitor screening method that can be used for the
      identification of the excipient-mediated precipitation inhibition of poorly
      soluble drugs. The impact of incubation temperature, shaking intensity, phase
      separation, inter- and intraday variability, cosolvent, and plate selection on
      the HT screening method performance was investigated. Additionally, the pipetting
      quality of the automated workstation, the correlation with the classical
      laboratory approach, and the practical implementation of the developed HT
      screening method using two model compounds are disclosed. Investigation of the HT
      method resulted in optimized experimental conditions, which showed low inter- and
      intraday variability (relative standard deviation [RSD]<5.88%). Higher shaking
      intensity (7 Hz) and incubation temperature (37 degrees C) resulted in a lower
      likelihood of obtaining false-negative results. The acceptable dimethyl sulfoxide
      concentration in the precipitation inhibitor screening assay was set to <=1%
      (v/v). All liquid dispensing steps resulted in an RSD of <3.4%, and an excellent
      correlation (R(2)=0.96, P<0.01) with the classical laboratory method was
      obtained. The practical implementation of the developed HT method was
      demonstrated by investigating the impact of 23 diverse excipients on the
      precipitation inhibition of two poorly soluble drugs (fenofibrate and
      carbamazepine). The screen resulted in the identification of hit excipients,
      which were not identical for fenofibrate and carbamazepine. This outcome
      emphasized that the HT screening approach is a reasonable starting point for
      searching for effective precipitation inhibitors, especially because the
      excipient-mediated precipitation inhibition effect is case specific and cannot be
      predicted in a straightforward manner.

PMID- 23116460
TI  - Prevalence of body-focused repetitive behaviors in three large medical colleges
      of Karachi: a cross-sectional study.
AB  - BACKGROUND: Body-focused repetitive behaviors (BFRBs) that include skin picking
      (dermatillomania), hair pulling (trichotillomania) and nail biting
      (onychophagia), lead to harmful physical and psychological sequelae.The objective
      was to determine the prevalence of BFRBs among students attending three large
      medical colleges of Karachi. It is imperative to come up with frequency to design
      strategies to decrease the burden and adverse effects associated with BFRBs among
      medical students. METHODS: A cross-sectional study was conducted among 210
      students attending Aga Khan University, Dow Medical College and Sind Medical
      College, Karachi, in equal proportion. Data were collected using a pre tested
      tool, "Habit Questionnaire". Diagnoses were made on the criteria that a student
      must be involved in an activity 5 times or more per day for 4 weeks or more.
      Convenience sampling was done to recruit the participants aged 18 years and above
      after getting written informed consent. RESULTS: The overall prevalence of BFRBs
      was found to be 46 (22%). For those positive for BFRBs, gender distribution was
      as follows: females 29 (13.9%) and males 17 (8.1%). Among these students, 19
      (9.0%) were engaged in dermatillomania, 28 (13.3%) in trichotillomania and 13
      (6.2%) in onychophagia. CONCLUSIONS: High proportions of BFRBs are reported among
      medical students of Karachi. Key health messages and interventions to reduce
      stress and anxiety among students may help in curtailing the burden of this
      disease which has serious adverse consequences.

PMID- 23116462
TI  - Pesticide photolysis in prairie potholes: probing photosensitized processes.
AB  - Prairie pothole lakes (PPLs) are glacially derived, ecologically important water
      bodies found in central North America and represent a unique setting in which
      extensive agriculture occurs within wetland ecosystems. In the Prairie Pothole
      Region (PPR), elevated pesticide use and increasing hydrologic connectivity have
      raised concerns about the impact of nonpoint source agricultural pollution on the
      water quality of PPLs and downstream aquatic systems. Despite containing high
      dissolved organic matter (DOM) levels, the photoreactivity of the PPL water and
      the photochemical fate of pesticides entering PPLs are largely unknown. In this
      study, the photodegradation of sixteen pesticides was investigated in PPL waters
      sampled from North Dakota, under simulated and natural sunlight. Enhanced
      pesticide removal rates in the irradiated PPL water relative to the control
      buffer pointed to the importance of indirect photolysis pathways involving
      photochemically produced reactive intermediates (PPRIs). The steady-state
      concentrations of carbonate radical, hydroxyl radical, singlet oxygen, and
      triplet-excited state DOM were measured and second-order rate constants for
      reactions of pesticides with these PPRIs were calculated. Results from this study
      underscore the role of DOM as photosensitizer in limiting the persistence of
      pesticides in prairie wetlands through photochemical reactions. 

PMID- 23116461
TI  - Synthesis and characterization of a melanoma-targeted fluorescence imaging probe
      by conjugation of a melanocortin 1 receptor (MC1R) specific ligand.
AB  - The incidence of malignant melanoma is rising more rapidly than that of any other
      cancer in the United States. The melanocortin 1 receptor (MC1R) is overexpressed
      in most human melanoma metastases, thus making it a promising target for imaging
      and therapy of melanomas. We have previously reported the development of a
      peptidomimetic ligand with high specificity and affinity for MC1R. Here, we have
      conjugated near-infrared fluorescent dyes to the C-terminus of this ligand via
      lysine-mercaptopropionic acid linkers to generate MC1R specific optical probes
      (MC1RL-800, 0.4 nM K(i); and MC1RL-Cy5, 0.3 nM K(i)). Internalization of the
      imaging probe was studied in vitro by fluorescence microscopy using engineered
      A375/MC1R cells and B16F10 cells with endogenous MC1R expression. The in vivo
      tumor targeting of MC1RL-800 was evaluated by intravenous injection of probe into
      nude mice bearing bilateral subcutaneous A375 xenograft tumors with low MC1R
      expression and engineered A375/MC1R tumors with high receptor expression.
      Melanotic B16F10 xenografts were also studied. Fluorescence imaging showed that
      the agent has higher uptake values in tumors with high expression compared to low
      (p < 0.05), demonstrating the effect of expression levels on image contrast-to
      noise. In addition, tumor uptake was significantly blocked by coinjection of
      excess NDP-alpha-MSH peptide (p < 0.05). In conclusion, the MC1R-specific imaging
      probe developed in this study displays excellent potential for the intraoperative
      detection of regional node involvement and for margin detection during melanoma
      metastasis resection.

PMID- 23116463
TI  - Co-occurrence of Haematoloechus complexus and Rhabdias joaquinensis in the plains
      leopard frog from Nebraska.
AB  - Species of Haematoloechus and Rhabdias both are ubiquitous lung parasites of
      frogs, yet surprisingly little research has been conducted on the interactions
      between these worms. In a small Nebraska stream, 256 Rhabdias joaquinensis and
      225 Haematoloechus complexus were found in the lungs of Lithobates (=Rana)
      blairi. Thirty-six of the 44 (82%) frogs were co-infected with H. complexus and
      R. joaquinensis whereas 5 (11%) frogs were infected with only 1 species and 3
      (7%) frogs were uninfected. Tests for association between H. complexus and R.
      joaquinensis found a significant positive relationship between the 2 parasites.
      Significant positive relationships in intensity of infection were found when both
      lungs were combined but not when lungs were considered individually. Tests for
      association between H. complexus and R. joaquinensis found no relationship
      between the worms in the anterior and posterior portions of the lungs. These data
      suggest that H. complexus and R. joaquinensis do not competitively exclude each
      other from the lungs of L. blairi in southeastern Nebraska.

PMID- 23116464
TI  - Beckwith Wiedemann imprinting defect found in leucocyte but not buccal DNA in a
      child born small for gestational age.
AB  - BACKGROUND: Loss of methylation (LOM) at imprinting control region (ICR) 1 or LOM
      at ICR 2 on chromosome 11p15 in leucocyte DNA is commonly used to diagnose the
      imprinting disorders Silver Russell syndrome (SRS) characterized by growth
      restriction or Beckwith Wiedemann syndrome (BWS) characterized by overgrowth,
      respectively. CASE PRESENTATION: A child was normally conceived and born by
      caesarian section to a healthy 19 year old smoking mother (G2P1) at 38 weeks
      gestation, with SGA (birthweight SDS -2.44), placenta weight 250g (normal
      histology), with an umbilical hernia and transient neonatal hypoglycemia but no
      other features of BWS.The methylation status at 11p15 region was initially
      investigated by multiplex ligation dependent probe amplification (MLPA).
      Subsequently, methylation-specific (ms) PCR was performed to screen for this and
      other imprinted loci abnormalities at PLAG1 (6q24), IGF2R (6q27), GRB10 (7p12),
      PEG1/MEST (7q32), DLK1 (14q32), SNRPN (15q11); PEG3 (19q32), NESPAS/GNAS
      (20q13).Leucocyte DNA methylation was normal at ICR1 but markedly reduced at ICR2
      using both MLPA and ms-PCR, and no other anomalies of imprinting were detected.
      Buccal DNA methylation was normal at all imprinted sites tested. CONCLUSION: This
      is the first report of an isolated LOM at ICR2 in leucocyte but not buccal DNA in
      a normally conceived singleton SGA child without overt SRS or BWS.

PMID- 23116465
TI  - Editorial: computational chemogenomics in drug design and discovery.

PMID- 23116467
TI  - Drug repurposing in chemical genomics: can we learn from the past to improve the
      future?
AB  - More needs to be done by the private sector to optimize the drug discovery and
      development pipeline. In addition, significant efforts should also be focused on
      the understanding of mechanism of diseases, on the characterization of unexplored
      biochemical pathways and on the validation of new protein targets. Chemical
      genomics, which uses chemical probes to help understand the complexity of
      biological systems at the gene and protein levels, has proven in recent years to
      be an important tool. Experimental and computational chemical genomic screenings
      have been used by the private sector and recently also by academia and non-profit
      institutions for drug repurposing or repositioning to find new indications for
      known drugs. A detailed overview of the current initiatives in drug repurposing,
      initiated by the major governmental funding agencies around the world is
      reported. The push towards greater efficiency is encouraging drug repurposing and
      other techniques in chemical genomics. Finding the best ways to improve
      translational research and accelerate the regulation of clinical phases means
      being able to launch safer drugs into the market faster.

PMID- 23116466
TI  - Compound activity prediction using models of binding pockets or ligand properties
      in 3D.
AB  - Transient interactions of endogenous and exogenous small molecules with flexible
      binding sites in proteins or macromolecular assemblies play a critical role in
      all biological processes. Current advances in high-resolution protein structure
      determination, database development, and docking methodology make it possible to
      design three-dimensional models for prediction of such interactions with
      increasing accuracy and specificity. Using the data collected in the Pocketome
      encyclopedia, we here provide an overview of two types of the three-dimensional
      ligand activity models, pocketbased and ligand property-based, for two important
      classes of proteins, nuclear and G-protein coupled receptors. For half the
      targets, the pocket models discriminate actives from property matched decoys with
      acceptable accuracy (the area under ROC curve, AUC, exceeding 84%) and for about
      one fifth of the targets with high accuracy (AUC > 95%). The 3D ligand property
      field models performed better than 95% in half of the cases. The high performance
      models can already become a basis of activity predictions for new chemicals.
      Family-wide benchmarking of the models highlights strengths of both approaches
      and helps identify their inherent bottlenecks and challenges.

PMID- 23116468
TI  - New insights in protein kinase conformational dynamics.
AB  - A significant portion of recent drug development efforts has been focused on
      protein kinases. More than a hundred different compounds are currently under
      clinical trials and nearly 30% of all the scientific articles in drug discovery
      are on protein kinase inhibitors. Protein kinases are very flexible targets and
      undergo significant conformational changes upon activation and during the
      catalytic cycle. This flexibility can be exploited in drug discovery. Some of the
      inactive states that emerge during the conformational changes are targeted by
      various inhibitors with a significant gain in selectivity. Here, we review the
      recent advances being made in understanding the details and the mechanism of
      these conformational changes thanks to the progress in molecular dynamics and
      free energy algorithms as well as to the availability of specialized computer
      hardware.

PMID- 23116469
TI  - QSARs, data and error in the modern age of drug discovery.
AB  - The legacy of the advances made in high-throughput screening (HTS) in the 1990's
      is a large source of public data from which models can be derived using QSAR
      methods. This paper will examine the integrity of these public data sources and
      the implications for model building.

PMID- 23116470
TI  - Target prediction of small molecules with information of key molecular
      interactions.
AB  - The knowledge about to which biomolecules a small molecule binds is highly
      valuable in the drug development process. Although analytical methods to dissect
      ligand-binding proteome have made substantial progress in the past decades, it is
      generally too costly, if not infeasible, to know where a small molecule binds at
      very high resolution. Computational prediction of binding partners of small
      chemical molecules has become a useful approach to evaluate their potential
      therapeutic applications or adverse effects. In this article two computational
      approaches that were adopted to perform target identification, namely, molecular
      docking and pharmacophore fitting, are reviewed. Both approaches enable the
      identification of key interactions between the biomolecules and the small
      molecules. Databases that can be used to further improve the implementation and
      the computational methods and to benchmark their performances are also included.

PMID- 23116472
TI  - New insights in atom-atom interactions for future drug design.
AB  - In silico medicinal chemistry investigates molecular systems that are too large
      to be tackled by medium to high level ab initio quantum chemistry. Only atomistic
      force fields can deliver rapid computation of energy required in sampling the
      many conformational and orientational degrees of freedom of a ligand within a
      protein pocket. However, the predictive reliability of a force field critically
      depends on the quality and realism of its energy function. Particularly, the
      electrostatic component of this energy needs to be as accurate as possible
      because druglike ligands and proteins are polar molecules, whose interaction does
      not just depend on shape. Surprisingly, the challenging problem of energy
      accuracy receives much less attention than it deserves. Docking results in the
      literature are still dependent on atomic point charges, which are inherently
      inaccurate at short and medium range. This has been known for decades but
      improved and more accurate methods have not (yet) found their way in mainstream
      in silico medicinal chemistry. Moreover, often the "details" of the electrostatic
      energy are poorly and not at all reported, as if they do not matter. This article
      attempts to inspire future docking algorithms with ideas from an approach called
      Quantum Chemical Topology (QCT). The way this method partitions energy and treats
      the electrostatic interaction should inject more realism into the current
      paradigm. The gap between the medicinal chemistry "world view" and that of
      physical and computational chemistry needs to narrow en route to reach the
      currently elusive goal to make docking work for the right reasons. We discuss in
      detail a path to make electrostatics drastically more realistic, based on novel
      ideas, some partially implemented.

PMID- 23116471
TI  - Enzyme informatics.
AB  - Over the last 50 years, sequencing, structural biology and bioinformatics have
      completely revolutionised biomolecular science, with millions of sequences and
      tens of thousands of three dimensional structures becoming available. The
      bioinformatics of enzymes is well served by, mostly free, online databases.
      BRENDA describes the chemistry, substrate specificity, kinetics, preparation and
      biological sources of enzymes, while KEGG is valuable for understanding enzymes
      and metabolic pathways. EzCatDB, SFLD and MACiE are key repositories for data on
      the chemical mechanisms by which enzymes operate. At the current rate of genome
      sequencing and manual annotation, human curation will never finish the functional
      annotation of the ever-expanding list of known enzymes. Hence there is an
      increasing need for automated annotation, though it is not yet widespread for
      enzyme data. In contrast, functional ontologies such as the Gene Ontology already
      profit from automation. Despite our growing understanding of enzyme structure and
      dynamics, we are only beginning to be able to design novel enzymes. One can now
      begin to trace the functional evolution of enzymes using phylogenetics. The
      ability of enzymes to perform secondary functions, albeit relatively
      inefficiently, gives clues as to how enzyme function evolves. Substrate
      promiscuity in enzymes is one example of imperfect specificity in protein-ligand
      interactions. Similarly, most drugs bind to more than one protein target. This
      may sometimes result in helpful polypharmacology as a drug modulates plural
      targets, but also often leads to adverse side-effects. Many chemoinformatics
      approaches can be used to model the interactions between druglike molecules and
      proteins in silico. We can even use quantum chemical techniques like DFT and
      QM/MM to compute the structural and energetic course of enzyme catalysed chemical
      reaction mechanisms, including a full description of bond making and breaking.

PMID- 23116473
TI  - Computational tools for in silico fragment-based drug design.
AB  - Fragment-based strategy in drug design involves the initial discovery of low
      molecular mass molecules. Owing to their small-size, fragments are molecular
      tools to probe specific sub-pockets within a protein active site. Once their
      interaction within the enzyme cavity is clearly understood and experimentally
      validated, they represent a unique opportunity to design potent and efficient
      larger compounds. Computer-aided methods can essentially support the
      identification of suitable fragments. In this review, available tools for
      computational drug design are discussed in the frame of fragmentbased approaches.
      We analyze and review (i) available commercial fragment libraries with respect to
      their properties and size, (ii) computational methods for the construction of
      such a library, (iii) the different strategies and software packages for the
      selection of the fragments with predicted affinity to a given target, and (iv)
      tools for the in silico linkage of fragments into an actual high-affinity lead
      structure candidate.

PMID- 23116474
TI  - Critically examining diversity in end-of-life family caregiving: implications for
      equitable caregiver support and Canada's Compassionate Care Benefit.
AB  - INTRODUCTION: Family (i.e., unpaid) caregiving has long been thought of as a
      'woman's issue', which ultimately results not only in gendered, but also
      financial and health inequities. Because of this, gender-based analyses have been
      prioritized in caregiving research. However, trends in current feminist
      scholarship demonstrate that gender intersects with other axes of difference,
      such as culture, socio-economic status, and geography to create diverse
      experiences. In this analysis we examine how formal front-line palliative care
      providers understand the role of such diversities in shaping Canadian family
      caregivers' experiences of end-of-life care. In doing so we consider the
      implications of these findings for a social benefit program aimed at supporting
      family caregivers, namely the Compassionate Care Benefit (CCB). METHODS: This
      analysis contributes to a utilization-focused evaluation of Canada's CCB, a
      social program that provides job security and limited income assistance to
      Canadian family caregivers who take a temporary leave from employment to provide
      care for a dying family member at end-of-life. Fifty semi-structured phone
      interviews with front-line palliative care providers from across Canada were
      conducted and thematic diversity analysis of the transcripts ensued. RESULTS:
      Findings reveal that experiences of caregiving are not homogenous and access to
      services and supports are not universal across Canada. Five axes of difference
      were commonly raised by front-line palliative care providers when discussing
      important differences in family caregivers' experiences: culture, gender,
      geography, lifecourse stage, and material resources. Our findings reveal
      inequities with regard to accessing needed caregiver services and resources,
      including the CCB, based on these axes of difference. CONCLUSIONS: We contend
      that without considering diversity, patterns in vulnerability and inequity are
      overlooked, and thus continually reinforced in health policy. Based on our
      findings, we demonstrate that re-framing categorizations of caregivers can expose
      specific vulnerabilities and inequities while identifying implications for the
      CCB program as it is currently administered. From a policy perspective, this
      analysis demonstrates why diversity needs to be acknowledged in policy circles,
      including in relation to the CCB, and seeks to counteract single dimensional
      approaches for understanding caregiver needs at end-of-life. Such findings
      illustrate how diversity analysis can dramatically enhance evaluative health
      policy research.

PMID- 23116475
TI  - Effect of covalent chemistry on the electronic structure and properties of carbon
      nanotubes and graphene.
AB  - In this Account, we discuss the chemistry of graphitic materials with particular
      reference to three reactions studied by our research group: (1) aryl radical
      addition, from diazonium precursors, (2) Diels-Alder pericyclic reactions, and
      (3) organometallic complexation with transition metals. We provide a unified
      treatment of these reactions in terms of the degenerate valence and conduction
      bands of graphene at the Dirac point and the relationship of their orbital
      coefficients to the HOMO and LUMO of benzene and to the Clar structures of
      graphene.  In the case of the aryl radical addition and the Diels-Alder
      reactions, there is full rehybridization of the derivatized carbon atoms in
      graphene from sp(2) to sp(3), which removes these carbon atoms from conjugation
      and from the electronic band structure of graphene (referred to as destructive
      rehybridization). The radical addition process requires an electron transfer step
      followed by the formation of a sigma-bond and the creation of a pi-radical in the
      graphene lattice, and thus, there is the potential for unequal degrees of
      functionalization in the A and B sublattices and the possibility of
      ferromagnetism and superparamagnetism in the reaction products.  With regard to
      metal functionalization, we distinguish four limiting cases: (a) weak
      physisorption, (b) ionic chemisorption, in which there is charge transfer to the
      graphitic structure and preservation of the conjugation and band structure, (c)
      covalent chemisorption, in which there is strong rehybridization of the graphitic
      band structure, and (d) covalent chemisorption with formation of an
      organometallic hexahapto-metal bond that largely preserves the graphitic band
      structure (constructive rehybridization). The constructive rehybridization that
      accompanies the formation of bis-hexahapto-metal bonds, such as those in (eta(6)
      SWNT)Cr(eta(6)-SWNT), interconnects adjacent graphitic surfaces and significantly
      reduces the internanotube junction resistance in single-walled carbon nanotube
      (SWNT) networks. The conversion of sp(2) hybridized carbon atoms to sp(3) can
      introduce a band gap into graphene, influence the electronic scattering, and
      create dielectric regions in a graphene wafer. However, the organometallic
      hexahapto (eta(6)) functionalization of the two-dimensional (2D) graphene pi
      surface with transition metals provides a new way to modify graphitic structures
      that does not saturate the functionalized carbon atoms and, by preserving their
      structural integrity, maintains the delocalization in these extended periodic pi
      electron systems and offers the possibility of three-dimensional (3D)
      interconnections between adjacent graphene sheets. These structures may find
      applications in interconnects, 3D-electronics, organometallic catalysis, atomic
      spintronics and in the fabrication of new electronic materials.

PMID- 23116476
TI  - Prayer at midlife is associated with reduced risk of cognitive decline in Arabic
      women.
AB  - Midlife habits may be important for the later development of Alzheimer's disease
      (AD). We estimated the contribution of midlife prayer to the development of
      cognitive decline. In a door-to-door survey, residents aged >=65 years were
      systematically evaluated in Arabic including medical history, neurological,
      cognitive examination, and a midlife leisure-activities questionnaire. Praying
      was assessed by the number of monthly praying hours at midlife. Stepwise logistic
      regression models were used to evaluate the effect of prayer on the odds of mild
      cognitive impairment (MCI) and AD versus cognitively normal individuals. Of 935
      individuals that were approached, 778 [normal controls (n=448), AD (n=92) and MCI
      (n=238)] were evaluated. A higher proportion of cognitively normal individuals
      engaged in prayer at midlife [(87%) versus MCI (71%) or AD (69%) (p<0.0001)].
      Since 94% of males engaged in prayer, the effect on cognitive decline could not
      be assessed in men. Among women, stepwise logistic regression adjusted for age
      and education, showed that prayer was significantly associated with reduced risk
      of MCI (p=0.027, OR=0.55, 95% CI 0.33-0.94), but not AD. Among individuals
      endorsing prayer activity, the amount of prayer was not associated with MCI or AD
      in either gender. Praying at midlife is associated with lower risk of mild
      cognitive impairment in women.

PMID- 23116478
TI  - Improved outcome of adults with aplastic anaemia treated with arsenic trioxide
      plus ciclosporin.

PMID- 23116477
TI  - Regulation of cerebral artery smooth muscle membrane potential by Ca2+-activated
      cation channels.
AB  - Arterial tone is dependent on the depolarizing and hyperpolarizing currents
      regulating membrane potential and governing the influx of Ca2+ needed for smooth
      muscle contraction. Several ion channels have been proposed to contribute to
      membrane depolarization, but the underlying molecular mechanisms are not fully
      understood. In this review, we will discuss the historical and physiological
      significance of the Ca2+-activated cation channel, TRPM4, in regulating membrane
      potential of cerebral artery smooth muscle cells. As a member of the recently
      described transient receptor potential super family of ion channels, TRPM4
      possesses the biophysical properties and upstream cellular signaling and
      regulatory pathways that establish it as a major physiological player in smooth
      muscle membrane depolarization.

PMID- 23116479
TI  - Gene expression studies of host response to Salmonid alphavirus subtype 3
      experimental infections in Atlantic salmon.
AB  - Salmonid alphavirus subtype-3 (SAV-3) infection in Atlantic salmon is exclusively
      found in Norway. The salmonid alphaviruses have been well characterized at the
      genome level but there is limited information about the host-pathogen interaction
      phenomena. This study was undertaken to characterize the replication and spread
      of SAV-3 in internal organs of experimentally infected Atlantic salmon and the
      subsequent innate and adaptive immune responses. In addition, suitability of a
      cohabitation challenge model for this virus was also examined. Groups of fish
      were infected by intramuscular injection (IM), cohabited (CO) or kept uninfected
      in a separate tank. Samples of pancreas, kidney, spleen, heart and skeletal
      muscles were collected at 2, 4 and 8 weeks post infection (wpi). Pathological
      changes were assessed by histology concurrently with viral loads and mRNA
      expression of immune genes by real time RT-PCR. Pathological changes were only
      observed in the pancreas and heart (target organs) of both IM and CO groups, with
      changes appearing first in the pancreas (2 wpi) in the former. Lesions with
      increasing severity over time coincided with high viral loads despite significant
      induction of IFN-alpha, Mx and ISG15. IFN-gamma and MHC-I were expressed in all
      tissues examined and their induction appeared in parallel with that of IL-10.
      Inflammatory genes TNF-alpha, IL-12 and IL-8 were only induced in the heart
      during pathology while T cell-related genes CD3epsilon, CD4, CD8, TCR-alpha and
      MHC-II were expressed in target organs at 8 wpi. These findings suggest that the
      onset of innate responses came too late to limit virus replication. Furthermore,
      SAV-3 infections in Atlantic salmon induce Th1/cytotoxic responses in common with
      other alphaviruses infecting higher vertebrates. Our findings demonstrate that
      SAV-3 can be transmitted via the water making it suitable for a cohabitation
      challenge model.

PMID- 23116480
TI  - Predictors of orthostatic hypotension in patients attending a transient ischaemic
      attack clinic: database study.
AB  - BACKGROUND: Orthostatic hypotension (OH) is common amongst the older population
      and is associated with morbidity and mortality. We sought to investigate
      predictors of OH to assist the clinician in identifying patients at risk. METHODS
      AND RESULTS: Database of 2696 patients attending a transient ischaemic attack
      (TIA) clinic between January 2006 and May 2009 was examined. Logistic regression
      models were constructed to determine clinical associates of OH. Demographics, co
      morbidities, cardiovascular risk factors and medications were included in the
      multivariate models. Simple data mining models in the form of rule sets were
      developed for each component and they were assessed for predictive accuracy. The
      best models were validated on a smaller sample. Prevalence of OH was 22.3% in the
      TIA clinic population (50.6% men, mean 72 years; 49.4% women, mean 75 years). A
      significant postural drop in systolic blood pressure (BP) (>= 20 mmHg) was more
      prevalent than a significant diastolic BP drop (>= 10 mmHg). Isolated systolic
      hypertension was common (52.4%). Common factors predicting a significant systolic
      and diastolic BP fall were older age, previous TIA, being a current smoker,
      having diabetes and the use of beta-blockers. Both mean arterial and pulse
      pressure (MAP and PP) derived from supine BP were significantly associated with
      OH. CONCLUSIONS: OH should be assessed routinely in TIA clinics. MAP and PP may
      provide information on the predictability of OH.

PMID- 23116481
TI  - Elemental concentrations of ambient particles and cause specific mortality in
      Santiago, Chile: a time series study.
AB  - BACKGROUND: The health effects of particulate air pollution are widely recognized
      and there is some evidence that the magnitude of these effects vary by particle
      component. We studied the effects of ambient fine particles (aerodynamic diameter
      < 2.5 MUm, PM(2.5)) and their components on cause-specific mortality in Santiago,
      Chile, where particulate pollution is a major public health concern. METHODS: Air
      pollution was collected in a residential area in the center of Santiago. Daily
      mortality counts were obtained from the National Institute of Statistic. The
      associations between PM(2.5) and cause-specific mortality were studied by time
      series analysis controlling for time trends, day of the week, temperature and
      relative humidity. We then included an interaction term between PM(2.5) and the
      monthly averages of the mean ratios of individual elements to PM2.5 mass.
      RESULTS: We found significant effects of PM(2.5) on all the causes analyzed, with
      a 1.33% increase (95% CI: 0.87-1.78) in cardiovascular mortality per 10 MUg/m(3)
      increase in the two days average of PM(2.5). We found that zinc was associated
      with higher cardiovascular mortality. Particles with high content of chromium,
      copper and sulfur showed stronger associations with respiratory and COPD
      mortality, while high zinc and sodium content of PM(2.5) amplified the
      association with cerebrovascular disease. CONCLUSIONS: Our findings suggest that
      PM(2.5) with high zinc, chromium, copper, sodium, and sulfur content have
      stronger associations with mortality than PM(2.5) mass alone in Santiago, Chile.
      The sources of particles containing these elements need to be determined to
      better control their emissions.

PMID- 23116482
TI  - CooVar: co-occurring variant analyzer.
AB  - BACKGROUND: Evaluating the impact of genomic variations (GV) on protein-coding
      transcripts is an important step in identifying variants of functional
      significance. Currently available programs for variant annotation depend on
      external databases or annotate multiple variants affecting the same transcript
      independently, which limits program use to organisms available in these databases
      or results in potentially incorrect or incomplete annotations. FINDINGS: We have
      developed CooVar (Co-occurring Variant Analyzer), a database-independent program
      for assessing the impact of GVs on protein-coding transcripts. CooVar takes GVs,
      reference genome sequence, and protein-coding exons as input and provides
      annotated GVs and transcripts as output. Other than similar programs, CooVar
      considers the combined impact of all GVs affecting the same transcript,
      generating biologically more accurate annotations. CooVar is operated from the
      command-line and supports standard file formats VCF, GFF/GTF, and GVF, which
      makes it easy to integrate into existing computational pipelines. We have
      extensively tested CooVar on worm and human data sets and demonstrate that it
      generates correct annotations in only a short amount of time. CONCLUSIONS: CooVar
      is an easy-to-use and lightweight variant annotation tool that considers the
      combined impact of GVs on protein-coding transcripts. CooVar is freely available
      at http://genome.sfu.ca/projects/coovar/.

PMID- 23116483
TI  - Site-specific PEGylated Exendin-4 modified with a high molecular weight trimeric
      PEG reduces steric hindrance and increases type 2 antidiabetic therapeutic
      effects.
AB  - The purpose of this study was to optimize an Exendin-4 (Ex4-Cys) site-specific
      PEGylation method with a high-molecular-weight trimeric PEG. Here, we describe
      the preparation of C-terminal specific PEGylated Ex4-Cys (C40-tPEG-Ex4-Cys),
      which was performed using cysteine and amine residue specific coupling reactions
      between Ex4-Cys and activated trimeric PEG. The C40-PEG-Ex4-Cys was obtained at
      high yields (~83%) and characterized by MALDI-TOF mass spectrometry. The receptor
      binding affinity of C40-PEG(5K)-Ex4-Cys was 3.5-fold higher than that of N
      terminal PEGylated Ex4-Cys (N(ter)-PEG(5K)-Ex4-Cys), and receptor binding by the
      trimeric PEG (tPEG; 23, 50 kDa) adduct was much higher than that of branched PEG
      (20 kDa). Furthermore, C40-tPEG(50K)-Ex4-Cys was found to have greater blood
      circulating t(1/2) and AUC(inf) values than native Ex4-Cys by 7.53- and 45.61
      fold, respectively. Accordingly, its hypoglycemic duration was much greater at
      59.2 h than that of native Ex4-Cys at 7.3 h, with a dose of 25 nM/kg. The results
      of this study show that C-terminal specific PEGylation using trimeric PEG is
      effective when applied to Ex4-Cys and suggest that C40-tPEG(50K)-Ex4-Cys has
      considerable potential as a type 2 antidiabetic agent.

PMID- 23116484
TI  - Oral immunogenicity of porcine reproductive and respiratory syndrome virus
      antigen expressed in transgenic banana.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) is a persistent
      threat of economically significant influence to the swine industry worldwide.
      Recombinant DNA technology coupled with tissue culture technology is a viable
      alternative for the inexpensive production of heterologous proteins in planta.
      Embryogenic cells of banana cv. 'Pei chiao' (AAA) have been transformed with the
      ORF5 gene of PRRSV envelope glycoprotein (GP5) using Agrobacterium-mediated
      transformation and have been confirmed. Recombinant GP5 protein levels in the
      transgenic banana leaves were detected and ranged from 0.021%-0.037% of total
      soluble protein. Pigs were immunized with recombinant GP5 protein by orally
      feeding transgenic banana leaves for three consecutive doses at a 2-week interval
      and challenged with PRRSV at 7 weeks postinitial immunization. A vaccination
      dependent gradational increase in the elicitation of serum and saliva anti-PRRSV
      IgG and IgA was observed. Furthermore, significantly lower viraemia and tissue
      viral load were recorded when compared with the pigs fed with untransformed
      banana leaves. The results suggest that transgenic banana leaves expressing
      recombinant GP5 protein can be an effective strategy for oral delivery of
      recombinant subunit vaccines in pigs and can open new avenues for the production
      of vaccines against PRRSV.

PMID- 23116485
TI  - The effect of ketoconazole on the pharmacokinetics and pharmacodynamics of
      inhaled fluticasone furoate and vilanterol trifenatate in healthy subjects.
AB  - AIM: To investigate the effects of the cytochrome P450 3A4 (CYP3A4) inhibitor
      ketoconazole on the pharmacokinetics (PK) and pharmacodynamics of fluticasone
      furoate (FF) and vilanterol trifenatate (VI). METHODS: Two double-blind,
      randomized, placebo-controlled, two-way crossover studies in healthy subjects. In
      study 1, subjects received single doses of ketoconazole (400 mg) or placebo on
      days 1-6, with a single dose of inhaled VI (25 MUg) on day 5. Pharmacodynamic and
      PK data were obtained up to 48 h following the VI dose. In study 2, subjects
      received once daily ketoconazole (400 mg) or placebo for 11 days, with FF/VI
      (200/25 MUg) for the final 7 days. Pharmacodynamic and PK data were obtained up
      to 48 h following the day 11 dose. RESULTS: In study 1, there was no effect of co
      administration of ketoconazole and VI on pharmacodynamic or PK parameters. In
      study 2, co-administration of ketoconazole and FF/VI had no effect on 0-4 h
      maximal heart rate or minimal blood potassium {treatment difference [90%
      confidence interval (CI)] -0.6 beats min(-1) (-5.8, 4.5) and 0.04 mmol l(-1) (
      0.03, 0.11), respectively}, whilst there was a 27% decrease in 24 h weighted mean
      serum cortisol [treatment ratio (90% CI) 0.73 (0.62, 0.86)]. Co-administration of
      ketoconazole increased [percentage change (90% CI)] FF area under the curve (0
      24) and maximal plasma concentration by 36% (16, 59) and 33% (12, 58),
      respectively, and VI area under the curve (0-t') and maximal plasma concentration
      by 65% (38, 97) and 22% (8, 38), respectively. CONCLUSION: Co-administration of
      FF/VI or VI with ketoconazole resulted in a less than twofold increase in
      systemic exposure to FF and VI. There was no increase in beta-agonist systemic
      pharmacodynamic effects, while serum cortisol was decreased by 27%. Co
      administration of FF/VI with strong CYP3A4 inhibitors has the potential to
      increase systemic exposure to both fluticasone furoate and vilanterol, which
      could lead to an increase in the potential for adverse reactions.

PMID- 23116486
TI  - Ligand binding studied by 2D IR spectroscopy using the azidohomoalanine label.
AB  - We explore the capability of the azidohomoalanine (Aha) as a vibrational label
      for 2D IR spectroscopy to study the binding of the target peptide to the PDZ2
      domain. The Aha label responds sensitively to its local environment and its peak
      extinction coefficient of 350-400 M(-1) cm(-1) is high enough to routinely
      measure it in the low millimolar concentration regime. The central frequency,
      inhomogeneous width and spectral diffusion times deduced from the 2D IR line
      shapes of the Aha label at various positions in the peptide sequence is discussed
      in relationship to the known X-ray structure of the peptide bound to the PDZ2
      domain. The results suggest that the Aha label introduces only a small
      perturbation to the overall structure of the peptide in the binding pocket.
      Finally, Aha is a methionine analog that can be incorporated also into larger
      proteins at essentially any position using protein expression. Altogether, Aha
      thus fulfills the requirements a versatile label should have for studies of
      protein structure and dynamics by 2D IR spectroscopy.

PMID- 23116487
TI  - Reversible rearrangements of Cu(II) cage complexes: solvent and anion influences.
AB  - The macrobicyclic mixed donor cage ligand AMME-N3S3sar (1-methyl-8-amino-3,13,16
      trithia-6,10,19-triazabicyclo[6.6.6]eicosane) is capable of binding to Cu(II) as
      either a hexadentate (N3S3) or tetradentate (N2S2) ligand. The "Cu-in"
      (hexadentate)/"Cu-out" (tetradendate) equilibrium for the {Cu(AMME-N3S3sar)}(2+)
      units is strongly influenced by both solvent (DMSO, MeCN, and water) and halide
      ions (Br(-) and Cl(-)). We have established a crucial role of the solvent in
      these processes through the formation of intermediate solvato complexes, which
      are substituted by incoming halide ions triggering a final isomerization
      reaction. Surprisingly, for reactions carried out in the usually strongly
      coordinating solvent water, the completely encapsulated N3S3-bound "Cu-in" form
      is dominant. Furthermore, the small amounts of the "Cu-out" form present in
      equilibrated DMSO or MeCN solutions revert entirely to the "Cu-in" form in
      aqueous media, thus preventing reaction with halide anions which otherwise lead
      to partial or even complete decomposition of the complex. From the kinetic,
      electrochemical, and EPR results, the existence of an outer-sphere H-bonded
      network of water molecules interacting with the complex inhibits egress of the
      Cu(II) ion from the cage ligand. This is extremely relevant in view of outer
      sphere interactions present in strongly hydrogen bonding solvents and their
      effects on Cu(II) complexation. 

PMID- 23116488
TI  - Efficient synthesis of alpha,beta-unsaturated alkylimines performed with allyl
      cations and azides: application to the synthesis of an ant venom alkaloid.
AB  - An efficient synthesis of alpha,beta-unsaturated alkylimines at low temperature
      using azides has been developed. Carbocations generated from allyl alcohols
      helped achieve a rapid conversion under mild conditions with azides to afford
      reactive alpha,beta-unsaturated imines. Hydroxy or alkoxy groups are essential
      for these transformations, and utilizing readily accessible allyl alcohols gave a
      wide extension of substrates. The efficiency of this novel method is demonstrated
      in the total synthesis of an iminium ant venom alkaloid.

PMID- 23116489
TI  - Centrocestus formosanus (Heterophyidae): human infections and the infection
      source in Lao PDR.
AB  - In Lao People's Democratic Republic (PDR), we detected 7 patients infected with
      Centrocestus formosanus (1-122 adult specimens) after praziquantel treatment and
      purgation, together with several other trematode species including Opisthorchis
      viverrini and Haplorchis taichui. The patients were all men, 23-42 yr-of-age.
      Three subjects were from Vientiane Municipality and 1 each were from Khammouane,
      Saravane, Champassak, and Xiengkhouang Province. The patients had frequently
      eaten raw freshwater fish and were experiencing variable degrees of epigastric
      pain and indigestion accompanied by occasional diarrhea, although the
      relationship of these symptoms with C. formosanus infection was unclear.
      Centrocestus formosanus specimens were ovoid, 0.46 mm (0.41-0.52 mm) long, and
      0.18 mm (0.16-0.20 mm) wide (n = 10) and were equipped with 32 circumoral spines
      on the oral sucker. The uterine eggs were 33.2 MUm long (31.8-34.9 MUm) and 18.5
      MUm wide (17.4-19.8 MUm) (n = 20). Analysis of the nucleotide sequence of the 18S
      ribosomal RNA gene of our specimens (Laotian isolate) revealed 100% homology with
      that of an isolate from the United States reported in GenBank. Several species of
      freshwater fish collected from Xiengkhouang Province revealed a 17.0% prevalence
      (9 of 53 fish examined) for C. formosanus metacercariae. The results suggest that
      human C. formosanus infections have been masked by other trematode infections.

PMID- 23116490
TI  - Daytime sleepiness in Japanese patients with multiple system atrophy: prevalence
      and determinants.
AB  - BACKGROUND: The recent SLEEMSA study that evaluated excessive daytime sleepiness
      (EDS) in Caucasian patients with multiple system atrophy (MSA) demonstrated that
      EDS was more frequent in patients (28%) than in healthy subjects (2%). However,
      the prevalence and determinants of EDS in other ethnic populations have not been
      reported to date. METHODS: We performed a single-hospital prospective study on
      patients with probable MSA. To ascertain the prevalence and determinants of EDS
      in Japanese MSA patients, we assessed the patients' degree of daytime sleepiness
      by using the Japanese version of the Epworth Sleepiness Scale (ESS). In addition,
      we investigated the effects of sleep-disordered breathing (SDB) and abnormal
      periodic leg movements in sleep (PLMS), which were measured by polysomnography,
      on the patients' ESS scores. RESULTS: A total of 25 patients with probable MSA
      (21 patients with cerebellar MSA and 4 patients with parkinsonian MSA) were
      included in this study. All patients underwent standard polysomnography. The mean
      ESS score was 6.2 +/- 0.9, and EDS was identified in 24% of the patients. SDB and
      abnormal PLMS were identified in 24 (96%) and 11 (44%) patients, respectively.
      The prevalences of EDS in patients with SDB and abnormal PLMS were 25% and 18%,
      respectively. No correlations were observed between ESS scores and the parameters
      of SDB or abnormal PLMS. CONCLUSIONS: The frequency of EDS in Japanese patients
      with MSA was similar to that in Caucasian MSA patients. SDB and abnormal PLMS
      were frequently observed in MSA patients, although the severities of these
      factors were not correlated with EDS. Further investigations using objective
      sleep tests need to be performed.

PMID- 23116491
TI  - Maternal mental health in the first 3-week postpartum: the impact of caregiver
      support and the subjective experience of childbirth - a longitudinal path model.
AB  - OBJECTIVE: Acute stress reactions (ASR) and postpartum depressive symptoms (PDS)
      are frequent after childbirth. The present study addresses the change and overlap
      of ASR and PDS from the 1- to 3-week postpartum and examines the interplay of
      caregiver support and subjective birth experience with regard to the development
      of ASR/PDS within a longitudinal path model. METHOD: A total of 219 mothers
      completed questionnaires about caregiver support and subjective birth experience
      (Salmon's Item List) at 48-6-h postpartum. ASR and PDS were measured for 1- and 3
      week postpartum. The Impact of Event Scale (IES) was used to assess ASR, and the
      Edinburgh Postnatal Depression Scale (EPDS) was used to assess PDS. RESULTS: ASR
      was frequent 1-week postpartum (44.7%) and declined till week 3 (24.8%, p <.001),
      while the prevalence of PDS was continuous (14.2% week 1; 12.6% week 3; p =
      .380). Favorable reports of caregiver support were related to better subjective
      childbirth experience, which was related to lower ASR and PDS (controlled for
      age, mode of delivery, parity, EDA and duration of childbirth). CONCLUSION: High
      quality of intrapartum care and positive birth experiences facilitate
      psychological adjustment in the first 3-week postpartum.

PMID- 23116492
TI  - Changes in regional brain monoaminergic activity and temporary down-regulation in
      stress response from dietary supplementation with l-tryptophan in Atlantic cod
      (Gadus morhua).
AB  - The brain monoamines serotonin (5-hydroxytryptamine; 5-HT) and dopamine (DA) both
      play an integrative role in behavioural and neuroendocrine responses to
      challenges, and comparative models suggest common mechanisms for dietary
      modulation of transmission by these signal substances in vertebrates. Previous
      studies in teleosts demonstrate that 7 d of dietary administration with L
      tryptophan (Trp), the direct precursor of 5-HT, suppresses the endocrine stress
      response. The present study investigated how long the suppressive effects of a
      Trp-enriched feed regimen, at doses corresponding to two, three or four times the
      Trp levels in commercial feed, last in juvenile Atlantic cod (Gadus morhua) when
      the fish are reintroduced to a diet with standard amino acid composition. We also
      wanted to determine whether Trp supplementation induced changes in brain
      monoaminergic neurochemistry in those forebrain structures innervated by DA and 5
      HTergic neurons, by measuring regional activity of DA and 5-HT in the lateral
      pallial regions (Dl) of the telencephalon and nucleus lateralis tuberis (NLT) of
      the hypothalamus. Dietary Trp resulted in a dose-dependent suppression in plasma
      cortisol among fish exposed to confinement stress on the first day following
      experimental diet; however, such an effect was not observed at 2 or 6 d after Trp
      treatment. Feeding the fish with moderate Trp doses also evoked a general
      increase in DA and 5-HT-ergic activity, suggesting that these neural circuits
      within the NLT and Dl may be indirectly involved in regulating the acute stress
      response.

PMID- 23116493
TI  - Serum thymidine kinase 1 levels correlates with FDG uptake and prognosis in
      patients with non small cell lung cancer.
AB  - CONTEXT: TK1 found to be elevated biomarker in many solid cancers. OBJECTIVES:
      The study aimed to assess the prognostic significance of a serum TK1 in patients
      with metastatic NSCLC. METHODS: The study included 48 consecutive patients, newly
      diagnosed with metastatic NSCLC, and 10 healthy volunteers. Serum TK1 activity
      determined by ELISA method. RESULTS: Patients with a bTK1 level >156 Du L(-1) had
      significantly shorter survival. TK1 level showed a strong correlation with
      primary tumor SUV(max). DISCUSSION AND CONCLUSION: The magnitude of maximum
      fluorodeoxyglucose uptake in primary tumors and the serum TK1 level in patients
      with metastatic NSCLC were found to be independent prognostic predictors of
      overall survival.

PMID- 23116494
TI  - The Bundaberg emergency response team.
AB  - A major crisis affected Bundaberg Hospital in 2005 following the exposure of the
      concerns about Dr Jayant Patel and the subsequent sudden exit of the Hospital
      Executive. The Bundaberg Emergency Response Team (BERT) was created as an
      emergency intervention whose brief was, over a 6-week period, to maintain the
      function of the hospital in the face of the community's loss of confidence in the
      service; to find out what had happened to Dr Patel's patients and to organise
      appropriate care and treatment for them. The authors acted as the senior members
      of BERT. Serious events such as these are rare and there was no framework to
      guide the team. BERT quickly established processes to assess the extent of harm
      to patients and to mobilise large scale clinical and counselling assistance for
      patients and staff. The team also managed the local health service, engagement
      with the community and assistance with the various investigations being conducted
      into Dr Patel. BERT was considered by the community and the former patients of Dr
      Patel to be an appropriate and professional response to the situation. The
      experience provides a framework for responses to these types of situations and
      herein we discuss key points for successful implementation.

PMID- 23116495
TI  - Toll-like receptor ligands induce the expression of interferon-gamma and
      interleukin-17 in chicken CD4+ T cells.
AB  - BACKGROUND: Toll-like receptors (TLRs) are evolutionarily conserved pattern
      recognition receptors that mediate host responses to pathogens. To date, at least
      10 different TLRs have been identified in chickens including TLR2, which binds
      lipopeptides and other similar ligands such as Pam3CSK4, TLR3, which binds double
      stranded RNA as well as synthetic molecules such as poly I:C, TLR4, which binds
      lipopolysaccharide (LPS), and TLR21, which binds CpG DNA motifs. In mammals, TLRs
      have been detected on CD4+ T cells where they mediate cellular survival,
      proliferation and the production of cytokines. However, the TLR-mediated
      responses in chicken CD4+ T cells remain to be determined. As such, the objective
      of the present study was to elucidate the kinetics of cytokine response to
      several different TLR ligands in chicken CD4+ T cells. RESULTS: The results
      suggest that these cells express TLRs 2, 3, 4 and 21 at the transcript level, and
      treatment with ligands for these TLRs significantly influenced the expression of
      the cytokines interferon (IFN)-gamma and interleukin (IL)-17, but not IL-4, IL-10
      and IL-13. Specifically, treatment with Pam3CSK4, poly I:C and LPS up-regulated
      IFN-gamma transcripts, while CpG ODN significantly down-regulated them. In
      contrast, at least one dose of each of the TLR ligands, except for Pam3CSK4,
      significantly down-regulated IL-17 transcripts. CONCLUSION: Chicken CD4+ T cells
      respond to ligands for TLRs 2, 3, 4 and 21 by up-regulating or down-regulating
      cytokine transcripts. Future studies may consider exploring how these TLR ligands
      may modulate other effector functions in chicken CD4+ T cells, as well as in
      other T cell subsets such as CD8+ T cells.

PMID- 23116496
TI  - Identifying structural domains of proteins using clustering.
AB  - BACKGROUND: Protein structures are comprised of modular elements known as
      domains. These units are used and re-used over and over in nature, and usually
      serve some particular function in the structure. Thus it is useful to be able to
      break up a protein of interest into its component domains, prior to similarity
      searching for example. Numerous computational methods exist for doing so, but
      most operate only on a single protein chain and many are limited to making a
      series of cuts to the sequence, while domains can and do span multiple chains.
      RESULTS: This study presents a novel clustering-based approach to domain
      identification, which works equally well on individual chains or entire
      complexes. The method is simple and fast, taking only a few milliseconds to run,
      and works by clustering either vectors representing secondary structure elements,
      or buried alpha-carbon positions, using average-linkage clustering. Each
      resulting cluster corresponds to a domain of the structure. The method is
      competitive with others, achieving 70% agreement with SCOP on a large non
      redundant data set, and 80% on a set more heavily weighted in multi-domain
      proteins on which both SCOP and CATH agree. CONCLUSIONS: It is encouraging that a
      basic method such as this performs nearly as well or better than some far more
      complex approaches. This suggests that protein domains are indeed for the most
      part simply compact regions of structure with a higher density of buried contacts
      within themselves than between each other. By representing the structure as a set
      of points or vectors in space, it allows us to break free of any artificial
      limitations that other approaches may depend upon.

PMID- 23116497
TI  - Is your life in balance?

PMID- 23116498
TI  - The power of the podium.

PMID- 23116500
TI  - Failure rates and associated risk factors of orthodontic miniscrew implants: a
      meta-analysis.
AB  - INTRODUCTION: Risk factors concerning orthodontic miniscrew implants have not
      been adequately assessed. In this systematic review, we summarize the knowledge
      from published clinical trials regarding the failure rates of miniscrew implants
      used for orthodontic anchorage purposes and identify the factors that possibly
      affect them. METHODS: Nineteen electronic databases and reference lists of
      included studies were searched up to February 2011, with no restrictions. Only
      randomized controlled trials, prospective controlled trials, and prospective
      cohort studies were included. Study selection and data extraction were performed
      twice. Failure event rates, relative risks, and the corresponding 95% confidence
      intervals were calculated. The random-effects model was used to assess each
      factor's impact. Subgroup and meta-regression analyses were also implemented.
      RESULTS: Fifty-two studies were included for the overall miniscrew implant
      failure rate and 30 studies for the investigation of risk factors. From the 4987
      miniscrew implants used in 2281 patients, the overall failure rate was 13.5% (95%
      confidence interval, 11.5-15.8). Failures of miniscrew implants were not
      associated with patient sex or age and miniscrew implant insertion side, whereas
      they were significantly associated with jaw of insertion. Certain trends were
      identified through exploratory analysis; however, because of the small number of
      original studies, no definite conclusions could be drawn. CONCLUSIONS:
      Orthodontic miniscrew implants have a modest small mean failure rate, indicating
      their usefulness in clinical practice. Although many factors seem to affect their
      failure rates, the majority of them still need additional evidence to support any
      possible associations.

PMID- 23116501
TI  - Insertion torque and success of orthodontic mini-implants: a systematic review.
AB  - INTRODUCTION: In this systematic review, we analyzed whether recommended maximum
      insertion torque values of 5 to 10 Ncm were associated with higher success rates
      of orthodontic mini-implants compared with mini-implants inserted with maximum
      insertion torque values beyond this range. Objective assessments of stability,
      variables that influence maximum insertion torque values, and adverse effect of
      interventions were also assessed in the studies selected for our PICO (patient
      problem or population, intervention, comparison, and outcomes) question. METHODS:
      Computerized and manual searches of the literature were conducted up to February
      24, 2012, for human studies that assessed these objectives. Our eligibility
      criteria selected studies that (1) used sample sizes of 10 or more, (2) recorded
      maximum insertion torque during the insertion of orthodontic mini-implants, (3)
      inserted implants with a diameter smaller than 2.5 mm, and (4) applied
      orthodontic forces for a minimum duration of 4 months. Confounding was assessed
      through the analysis of risk of bias, and the validity of outcomes was rated
      according to the GRADE approach. The Cochrane Handbook for Systematic Reviews of
      Interventions was our main guideline for the methodology. RESULTS: Seven
      nonrandomized studies met the eligibility criteria. All associations between
      specific maximum insertion torque values and success were based on literature
      rated as having low quality. The reasons for these judgments included subjective
      definitions of success, poor-quality torque sensors, and high risks for
      selection, performance, detection, and reporting biases. A risk of multiple
      publication bias was also suspected. All associations between maximum insertion
      torque and factors related to implant, patient, location, and surgery were
      rejected; few studies reported on adverse effects. CONCLUSIONS: Currently, no
      evidence indicates that specific maximum insertion torque levels are associated
      with higher success rates for orthodontic mini-implants. Additional research on
      this topic is therefore necessary. The following guidelines for future studies
      are suggested: (1) systematically review the animal and laboratory literature,
      (2) perform maximum insertion torque tests on artificial bone, (3) test
      associations in animal studies before conducting clinical trials, (4) test
      associations between maximum insertion torque and the stability of orthodontic
      mini-implants with objective quantitative recordings rather than subjective
      qualitative measures, (5) measure maximum insertion torque with digital sensors
      rather than with mechanical devices, (6) assess the stability of orthodontic mini
      implants at preestablished times, (7) consult our risk-of-bias analysis, and (8)
      analyze the adverse effects of interventions.

PMID- 23116502
TI  - Effect of soft laser in bone repair after expansion of the midpalatal suture in
      dogs.
AB  - INTRODUCTION: The purpose of this research was to study the influence of soft
      laser treatment on the process of bone repair after expansion of the midpalatal
      suture. METHODS: The sample for this case-control experimental study was 11 dogs.
      They were randomly divided into 2 groups, both of which underwent rapid maxillary
      expansion with a hyrax appliance. The animals in group 1 were also treated with
      laser therapy. They were killed, and histologic specimens of the palatal suture
      were prepared. The Student t test was applied for independent data, and the Mann
      Whitney test was used for nonparametric data. RESULTS: A significant difference
      was observed in the quality of the palatal sutures between the animals in groups
      1 and 2. The connective tissues of the sutures in the group 1 animals were
      similar to the original configurations, with more advanced osteogenesis and
      fibrogenesis, compared with those of group 2. CONCLUSIONS: Soft laser appears to
      influence the behavior of the repair process, contributing to suture
      reorganization and palatal bone osteogenesis during and after expansion.

PMID- 23116503
TI  - Bisphosphonates as a risk factor for adverse orthodontic outcomes: a
      retrospective cohort study.
AB  - INTRODUCTION: Bisphosphonates are a class of drugs commonly prescribed to treat
      osteoporosis. They act by decreasing the resorption of bone. Since tooth movement
      depends on bone remodeling, these drugs can impact orthodontic treatment. The
      purpose of this study was to evaluate the extent to which bisphosphonate therapy
      is a risk factor for poor orthodontic outcomes. METHODS: Orthodontists were
      invited to participate in the study by performing case reviews of women over age
      50 who were treated from 2002 through 2008. Women who used bisphosphonates were
      compared with women who did not have a history of bisphosphonate use. Outcomes
      assessed included treatment time, osteonecrosis of the jaws, incisor alignment,
      incomplete space closure, and root parallelism. RESULTS: The records for 20
      subjects with bisphosphonate exposure were collected, as well as records for 93
      subjects without bisphosphonate exposure. In patients undergoing extractions,
      treatment times were significantly longer if they had a history of bisphosphonate
      use. No occurrences of osteonecrosis of the jaws were reported, nor did patients
      end treatment with incisor alignment discrepancies greater than 1 mm, regardless
      of bisphosphonate exposure. Among patients with extractions or initial spacing,
      there were higher odds of incomplete space closure (odds ratio, 13) and poor root
      parallelism (odds ratio, 26) at the end of treatment for patients using
      bisphosphonates. CONCLUSIONS: Bisphosphonate use is associated with longer
      treatment times among extraction patients, increased odds of poor space closure,
      and increased odds of poor root parallelism.

PMID- 23116505
TI  - Mandibular anterior bony support and incisor crowding: Is there a relationship?
AB  - INTRODUCTION: The aim of this study was to test the null hypothesis that
      increased irregularity of the mandibular incisors is associated with a reduction
      in the alveolar support on cone-beam computed tomographic sections. METHODS: From
      a sample of 1100 digital volumetric tomographs, 125 tomographs of subjects with
      Class I malocclusion (mean age, 21.6 +/- 4.8 years) were selected for this study.
      An irregularity index was used to categorize these tomographs as having mild,
      moderate, or severe crowding. All tomographs were taken by using an iCAT (Imaging
      Sciences International, Hatfield, Pa) imaging device. The following parameters
      were measured on the sections corresponding to the 4 mandibular incisors with the
      iCAT software: height, thickness, and area of the entire symphysis; height,
      thickness, and area of the cancellous bone of the symphysis; and distance between
      the vestibular and lingual cortices. For the statistical evaluation, independent
      samples t test, analysis of variance, and the Tukey HSD test were used at an
      alpha level 0.05. The Pearson correlation coefficient and a simple linear
      regression were calculated to determine the relationship between mandibular
      anterior bony support and incisor crowding. RESULTS: Almost all mandibular
      anterior bone measurements were greater in the male subjects than in the female
      subjects (height of the mandibular symphysis, P <0.001; cancellous bone height, P
      <0.001). Female subjects with mild crowding had higher values for cancellous bone
      height (P = 0.025) and vestibular cancellous bone thickness (P = 0.004) than did
      those with severe crowding. However, no differences were detected in the male
      subjects. Additionally, significant correlations were determined between incisor
      crowding and thickness of the mandibular symphysis, cancellous bone thickness,
      and the vestibular part of cancellous bone thickness in female subjects.
      CONCLUSIONS: Significant relationships were found between the measures of
      mandibular incisor crowding and basal bone dimensions in female subjects. Except
      for the vestibular part of cancellous bone thickness, all mandibular incisor bone
      measurements were greater in the male subjects than in the female subjects.

PMID- 23116504
TI  - Dental arch dimensions of adolescent Kuwaitis with untreated ideal occlusion:
      variation and validity of proposed expansion indexes.
AB  - INTRODUCTION: The purposes of this study were to analyze the variations in dental
      arch dimensions of a large representative sample of adolescent Kuwaitis with
      untreated almost ideal occlusion and to test the validity of proposed expansion
      indexes and multivariate linear regression with inclusion of lateral and
      posteroanterior cephalometric parameters for estimation of dental arch width.
      METHODS: Study models and both lateral and posteroanterior cephalograms of 143
      Kuwaitis, aged 13 to 14 years, clinically diagnosed with untreated almost ideal
      occlusion during screening of a population-based sample, were examined. Maxillary
      and mandibular arch dimensions were measured by using a digital caliper accurate
      to 0.01 mm, and cephalometric parameters were measured electronically. RESULTS:
      All dimensions were greater in boys than in girls (P <0.001) and demonstrated
      wide individual variations. Maxillary arch-width estimates according to 3
      proposed expansion indexes differed from the actual dimensions (P <0.001), with
      more than 60% of the dimensions having discrepancies greater than 1.0 mm and
      explained variances from 0.12 to 0.20. Multivariate linear regression with
      inclusion of cephalometric parameters provided better estimates, with explained
      variances from 0.29 to 0.44. CONCLUSIONS: The tested expansion indexes provide
      poor estimates of maxillary arch widths, with low explained variances.
      Multivariate linear regression provides better estimates, with moderate explained
      variances.

PMID- 23116506
TI  - Insulin-like growth factor I: a biologic maturation indicator.
AB  - INTRODUCTION: Determination of the maturation level and the subsequent evaluation
      of growth potential during preadolescence and adolescence are important for
      optimal orthodontic treatment planning and timing. This study was undertaken to
      evaluate the applicability of insulin-like growth factor I (IGF-I) blood level as
      a maturation indicator by correlating it to the cervical vertebral maturation
      index. METHODS: The study was conducted with 120 subjects, equally divided into
      60 males (ages, 10-18 years) and 60 females (ages, 8-16 years). A lateral
      cephalometric radiograph and a blood sample were taken from each subject. For
      each subject, cervical vertebral maturation and IGF-I serum level were assessed.
      Mean values of IGF-I in each stage of cervical vertebral maturation were
      calculated, and the means in each stage were statistically compared with those of
      the other stages. RESULTS: The IGF-I mean value at each cervical vertebral
      maturation stage was statistically different from the mean values at the other
      stages. The highest mean values were observed in stage 4, followed by stage 5 in
      males and stage 3 in females. CONCLUSIONS: IGF-I serum level is a reliable
      maturation indicator that could be applied in orthodontic diagnosis.

PMID- 23116508
TI  - Cephalometric evaluation of adenoids: an analysis of current methods and a
      proposal of a new assessment tool.
AB  - INTRODUCTION: Although the scientific literature recognizes that lateral
      cephalometric radiographs might be clinically useful, there is no consensus in
      relation to the best parameter available. Therefore, this research was aimed at
      evaluating current radiographic assessment methods designed to investigate
      adenoid hypertrophy and nasopharyngeal obstruction. METHODS: Children from 4 to
      14 years old with nasal obstruction or oral breathing complaints, suspected to be
      caused by adenoid hypertrophy, received cephalometric examinations. One hundred
      twenty radiographic records were evaluated according to several current methods,
      and data were compared with respective gold-standard videonasopharyngoscopic
      examinations, in relation to the percentage of choanal obstruction. RESULTS:
      Groups derived from a grading system had significantly different percentages of
      choanal obstruction. However, this parameter showed low sensitivity. Significant
      but moderate correlations were observed between most of the quantitative
      radiographic parameters and the percentage of choanal obstruction. Alternatively,
      a regression model was introduced; it demonstrated satisfactory ability to
      predict choanal obstruction percentage. Despite limitations, this model could
      also distinguish patients who might benefit from referral to otolaryngologic
      care. CONCLUSIONS: Current adenoid assessment methods have significant
      limitations. A novel assessment method introduced here might be clinically
      useful.

PMID- 23116507
TI  - Association between CYP19A1 genotype and pubertal sagittal jaw growth.
AB  - INTRODUCTION: Sagittal jaw growth is influenced during puberty by a ratio of
      androgens and estrogens. The CYP19A1 (formerly CYP19) gene encodes the cytochrome
      P450 enzyme aromatase (estrogen synthetase), which converts testosterone to
      estrogen. Genetic variations including single nucleotide polymorphisms might
      regulate CYP19A1 gene expression or the function of the aromatase protein and
      thus influence sagittal jaw growth. METHODS: The annual sagittal jaw growth in 92
      pubertal orthodontic patients was determined by using pretreatment and
      posttreatment cephalometric radiographs. Single nucleotide polymorphisms
      rs2470144 and rs2445761 were genotyped and haplotypes constructed. Associations
      between genotypes or haplotypes and the annual sagittal growth were estimated by
      using JMP (version 9.0; SAS Institute, Cary, NC). RESULTS: Two single nucleotide
      polymorphisms were significantly associated with average differences in annual
      sagittal jaw growth in boys. Haplotype analysis demonstrated that haplotypes
      T(rs2470144)T(rs2445761) and C(rs2470144)T(rs2445761) had significant effects on
      annual sagittal maxillary growth and on mandibular growth in boys. No association
      was found in girls. CONCLUSIONS: A quantitative trait locus that influences male
      pubertal sagittal jaw growth might exist in the CYP19A1 gene, and single
      nucleotide polymorphisms rs2470144 and rs2445761 might be inside this
      quantitative trait locus or be linked to it.

PMID- 23116509
TI  - Do Class III patients have a different growth spurt than the general population?
AB  - INTRODUCTION: Understanding the timing and length of the growth spurt of Class
      III prognathic patients is fundamental to the strategy of interceptive orthopedic
      orthodontics as well as to the timing of orthognathic surgery. Consequently, this
      study was undertaken to determine whether there are any significant differences
      in the stature growth pattern of Class III subjects compared with non-Class III
      subjects and the general population. METHODS: Twelve-year longitudinal stature
      growth data were collected for 402 randomly selected adolescents in the general
      population, 55 Class III mandibular prognathic patients, and 37 non-Class III
      patients. The growth data were analyzed by using the traditional linear
      interpolation method and nonlinear growth functions. The 6 stature growth
      parameters were measured: age at takeoff, stature at takeoff, velocity at
      takeoff, age at peak height velocity, stature at peak height velocity, and
      velocity at peak height velocity. Comparisons in the stature growth parameters
      and 15 cephalometric variables among the general population, Class III subjects,
      and non-Class III subjects were made with multivariate analysis. RESULTS:
      Patients with Class III prognathism did not have different growth parameters
      compared with Class II subjects or the general population. CONCLUSIONS: This
      study does not allow meaningful conclusions with regard to the relationship of
      mandibular size and stature growth pattern. The application of nonlinear growth
      curves vs the traditional linear interpolation method was also discussed.

PMID- 23116510
TI  - Unusual orthodontic approach to a maxillary canine-premolar transposition and a
      missing lateral incisor with long-term follow-up.
AB  - In this case report, we present an unusual approach that was used to treat a 14
      year-old patient with a bilateral canine-premolar transposition and a missing
      maxillary lateral incisor. The orthodontic treatment involved maintaining the
      transposition and creating a space for lateral incisor replacement. Toward the
      end of the treatment, accentuated buccal root torque was performed, and lateral
      group function was established to improve the treatment outcome. Finally, an
      ideal esthetic and functional occlusion was achieved. The 8-year posttreatment
      follow-up records show the stability of this treatment.

PMID- 23116511
TI  - Segmental distraction osteogenesis with modified LeFort II osteotomy for a
      patient with craniosynostosis.
AB  - In this article, we report successful orthodontic treatment combined with
      segmental distraction osteogenesis after a modified LeFort II osteotomy in a
      patient with craniosynostosis. An 8-year-old boy diagnosed with craniosynostosis
      had a dished-in face, an anterior crossbite, and a skeletal Class III jaw
      relationship because of midfacial hypoplasia. At the age of 13 years 6 months,
      the maxillary second and mandibular first premolars were extracted, and leveling
      and alignment of both arches was started with preadjusted edgewise appliances. At
      age 14 years 11 months, the patient had a modified LeFort II osteotomy, and the
      maxillary segment was advanced 7 mm and fixed to the zygomatic bone. At the same
      time, segmental distraction osteogenesis was started with a rigid external
      distraction system, and the nasal segment was advanced for 20 days at a rate of
      1.0 mm per day. The total active treatment period was 40 months. As a result of
      the modified segmental distraction osteogenesis, significant improvement of his
      severe midfacial hypoplasia was achieved without excessive advancement of the
      maxillary dentition. Both the facial profile and the occlusion were stable after
      1 year of retention. However, the nasal segment relapsed 1.4 mm during the 1.5
      years after the segmental distraction osteogenesis. Evaluation of the stability
      and retention suggests that some overcorrection in midfacial advancement is
      recommended.

PMID- 23116512
TI  - Regional odontodysplasia: orthodontic treatment and transplantation of premolars.
AB  - Regional odontodysplasia is a rare and unique dental anomaly involving both
      dentitions, but mostly the teeth of 1 quadrant. This report describes the
      combined surgical and orthodontic treatment of a boy with regional
      odontodysplasia. The mandibular right central and lateral incisors and the canine
      (as well as the deciduous predecessors) were affected. In a 2-step procedure, the
      maxillary right and left second premolars were autotransplanted to the affected
      area. The extraction sites in the maxilla were closed, and a good functional
      occlusion was established.

PMID- 23116513
TI  - Three-dimensional retraction of anterior teeth with orthodontic miniplates in
      patients with temporomandibular disorder.
AB  - Vertical dimension control is critical for adults with Class II high-angle
      malocclusions. If the patient has a temporomandibular disorder, this requirement
      is exacerbated. When extraction is planned, the treatment challenge is further
      increased. This article reports on a new biomechanical design (C-therapy)
      appropriate for anterior segment retraction with excellent control of the
      vertical dimension, even in a Class II high-angle patient with a
      temporomandibular disorder. Maximum retraction of the maxillary anterior segment
      can be achieved with a lingual retractor and a palatal miniplate without
      appliances on the maxillary posterior segments. Mandibular anterior vertical
      height was well controlled by a second miniplate in the mental region. This
      device also contributed to mandibular anchorage reinforcement. A patient with
      temporomandibular disorder symptoms treated with this approach is shown.

PMID- 23116514
TI  - CAD/CAM/AM applications in the manufacture of dental appliances.
AB  - The purposes of this study were to apply the latest developments in additive
      manufacturing (AM) construction and to evaluate the effectiveness of these
      computer-aided design and computer-aided manufacturing (CAD/CAM) techniques in
      the production of dental appliances. In addition, a new method of incorporating
      wire into a single build was developed. A scanner was used to capture 3
      dimensional images of Class II Division 1 dental models that were translated onto
      a 2-dimensional computer screen. Andresen and sleep-apnea devices were designed
      in 3 dimensions by using FreeForm software (version 11; Geo Magics SensAble
      Group, Wilmington, Mass) and a phantom arm. The design was then exported and
      transferred to an AM machine for building.

PMID- 23116516
TI  - The effect size.

PMID- 23116515
TI  - Litigation and legislation: problems of our own making: a view from both sides of
      the coin.

PMID- 23116518
TI  - Antidepressant use and gestational hypertension: does evidence support causality?
      Reply letter.

PMID- 23116517
TI  - Optimization of multivalent bispecific antibodies and immunocytokines with
      improved in vivo properties.
AB  - Multifunctional antibody-based biologics, such as bispecific antibodies and
      immunocytokines, can be difficult to produce with sufficient yield and stability,
      and often exhibit inferior pharmacokinetics. Dock-and-Lock (DNL) is a modular
      method that combines recombinant engineering with site-specific conjugation,
      allowing the construction of various complex, yet defined, biostructures with
      multivalency and multispecificity. The technology platform exploits the natural
      interaction between two interactive human protein binding domains that are
      modified to provide covalent fusion. We explored the potential application of a
      new class of IgG-based DNL modules with an anchor domain fused at the C-terminal
      end of the kappa light chain (C(k)), instead of the C-terminal end of the Fc. Two
      C(k)-derived prototypes, an anti-CD22/CD20 bispecific hexavalent antibody,
      comprising epratuzumab (anti-CD22) and four Fabs of veltuzumab (anti-CD20), and a
      CD20-targeting immunocytokine, comprising veltuzumab and four molecules of
      interferon-alpha2b, were compared to their Fc-derived counterparts. The Ck-based
      conjugates exhibited superior Fc-effector functions in vitro, as well as improved
      pharmacokinetics, stability, and anti-lymphoma activity in vivo. These results
      favor the selection of DNL conjugates with the C(k)-design for future clinical
      development.

PMID- 23116519
TI  - Maternal hypertension induced by NO blockade does not program adult metabolic
      diseases in growth-restricted rat fetuses.
AB  - OBJECTIVE: Preeclampsia is a frequent and potentially lethal placental
      insufficiency pathology causing maternal hypertension and proteinuria, as well as
      a high rate of intrauterine growth retardation (IUGR) in offspring. Reduced
      nitric oxide (NO) production may play a role in the mechanisms of this disease.
      As exposure to adverse early life environment and IUGR has been proposed to
      increase cardiometabolic diseases risk, we investigated in rats the effects of
      maternal NO blockade on growth and metabolic phenotype of offspring. MATERIAL AND
      METHODS: Osmotic pumps were implanted in pregnant rats at E17 and diffused saline
      or L-NAME (50mg/day), a nitric oxide synthesis inhibitor. At birth, IUGR male
      newborns without limb defects were selected. Body growth, feeding behavior and
      glucose tolerance were evaluated in offspring. Organs weights, plasma level of
      several metabolic hormones and genes expressions were determined in fasted 9month
      old rats. RESULTS: L-NAME mothers had elevated blood pressure at E20. Male
      offspring from L-NAME mothers had a markedly reduced birth weight and developed
      postnatal catch-up growth during lactation. Some L-NAME newborns presented some
      limb defects but were not selected in this study (1/3 of all pups). Improved
      glucose tolerance and hyperphagia after fasting were found in 3-month-old L-NAME
      rat but not thereafter. In 9-month-old L-NAME rats, a moderate increase of food
      intake during the light phase and, after fasting, an augmentation of plasma
      insulin and a reduction of brown adipose tissue (BAT) deposit were found
      associated with an increased expression of UCP-1 mRNA in this tissue.
      CONCLUSIONS: Despite IUGR and postnatal catch up growth, male rats exposed to L
      NAME did not develop metabolic diseases when limb defects were not induced by L
      NAME. We postulate that maternal hypertension during late gestation is not a
      major 'programming' metabolic factor for offspring.

PMID- 23116521
TI  - The heart of health care: parents' perspectives on patient safety.
AB  - Behind the wall of silence in health care are the unanswered questions of parents
      whose children experienced harm at the hands of their caregivers. In an industry
      where information and communication are crucial to quality, parents' voices often
      go unheard. Although that has begun slowly to change, providers could benefit
      from following the HEART model of service recovery, which includes hearing the
      concerns of patients and their families, empathizing with them, apologizing when
      care goes wrong, responding to parents' concerns with openness, and thanking the
      patient and family.

PMID- 23116520
TI  - More effective dithiocarbamate derivatives inhibiting carbonic anhydrases,
      generated by QSAR and computational design.
AB  - Dithiocarbamates (DTC) are promising compounds with potential applications in
      antitumoral and glaucoma therapy. Our aim is to understand molecular features
      affecting DTC interaction with carbonic anhydrases (CAs), zinc-containing enzymes
      maintaining acid-base balance in blood and other tissues. To this end, we
      generate QSAR models based on a compound series containing 25 DTC, inhibitors of
      four human (h) CAs isoforms: hCA I, II, IX and XII. We establish that critical
      physicochemical parameters for DTC inhibitory activity are: hydrophobic,
      electronic, steric, topological and shape. The predictive power of our QSAR
      models is indicated by significant values of statistical coefficients: cross
      validated correlation q(2) (0.55-0.73), fitted correlation r(2) (0.75-0.84) and
      standard error of prediction (0.47-0.23). Based on the established QSAR
      equations, we analyse 22 new DTC derivatives and identify DTC dicarboxilic acids
      derivatives and their esters as potentially improved inhibitors of CA I, II, IX
      and XII.

PMID- 23116522
TI  - Computerized provider order entry and patient safety.
AB  - Medication errors can lead to significant morbidity and mortality for patients.
      Children are particularly vulnerable to medication errors. A strategy for
      reducing medication errors and the harm resulting from these errors is use of
      computerized provider order entry (CPOE). This article examines the frequency and
      nature of prescribing errors for pediatric patients. Also discussed are the
      proposed benefits from CPOE use, including elimination of eligibility errors,
      ensuring completeness in prescribing fields, reduction in transcription errors,
      and improved prescribing practices through the use of clinical decision support.
      The literature on the effect of CPOE in actual use is explored, as are policy
      implications and directions for future research.

PMID- 23116523
TI  - The role of "smart" infusion pumps in patient safety.
AB  - "Smart" infusion pumps are medication delivery devices that use a combination of
      computer technology and drug libraries to limit the potential for dosing errors.
      The evidence for their impact is limited: they have been shown to prevent some
      errors but there are minimal data linking the devices to reducing harm. Reasons
      for the limited impact include poor design leading to usability issues including
      programming errors, varying degrees of end-user acceptance, and their contingent
      nature. Iterative user-centered design, coupled with network and real-time
      monitoring of alerts may enhance the impact of these devices.

PMID- 23116524
TI  - Automated detection of adverse events in children.
AB  - Voluntary reporting has been the standard method for identifying adverse events
      in hospitals, yet its effectiveness at identifying a comprehensive array of
      adverse events has always been in question. The electronic health record (EHR)
      contains clinical data that can be systematically reviewed to identify adverse
      events and improve adverse event detection. Active use of an automated trigger
      tool that is embedded in an EHR can identify systematic issues with delivery of
      high-risk medications and is cost-effective and efficient. Further development of
      an automated adverse event detection protocol for pediatrics is needed to apply
      this approach systematically across pediatric institutions.

PMID- 23116526
TI  - Reducing mortality related to adverse events in children.
AB  - Since the launch of the 100,000 Lives Campaign by the Institute for Healthcare
      Improvement (IHI), preventing medical adverse events to reduce avoidable
      mortality has emerged as a central focus for health care providers, institutions,
      regulators, insurance companies, and patients. Evidence-based interventions
      targeting the 6 interventions in the campaign have been associated with a
      reduction in preventable hospital deaths in the United States. The
      generalizability of the IHI's campaign to the pediatric population is only partly
      applicable. Pediatric experiences with rapid response teams and preventing
      central-line infections parallel the published experience of adults, with promise
      to significantly reduce preventable pediatric mortality.

PMID- 23116525
TI  - Is preventable harm the right patient safety metric?
AB  - Despite increasing attention and discussion, patient harm remains an important
      issue in health care. Defining and identifying harm remains challenging, and
      little standardization in approach exists. This summary describes an approach to
      identifying hospital-wide preventable harm with focused safety efforts using the
      Preventable Harm Index as a measure of progress and as a metric to motivate
      improvement. Our hospital's significant decrease in serious safety events,
      mortality, and preventable harm is outlined.

PMID- 23116527
TI  - Standardization of case reviews (morbidity and mortality rounds) promotes patient
      safety.
AB  - The morbidity and mortality conference (M&M) is a long-standing practice in
      medicine. Originally created to identify errors and improve care, the primary
      focus of M&M has moved toward an emphasis on education of trainees. A structured
      format for the M&M conference can help the interdisciplinary team address causes
      of adverse patient outcomes and identify opportunities for systems improvement.

PMID- 23116528
TI  - Sleep science, schedules, and safety in hospitals: challenges and solutions for
      pediatric providers.
AB  - Sleep deprivation is common among resident physicians and clinical fellows.
      Current evidence about sleep science, performance, shift work, and medical errors
      consistently demonstrates positive impact from reduction of excessive duty hours,
      particularly when shift length is shortened. This article provides an overview of
      this literature, highlighting research on diminished physician cognitive
      performance due to sleep deprivation and the increase in the number of medical
      errors that is seen under these conditions. Accreditation Council on Graduate
      Medical Education trainee duty hour guidelines are reviewed. Practical approaches
      to evidence-based scheduling of shift-work are also discussed, with attention to
      improving patient safety.

PMID- 23116530
TI  - Patient safety in ambulatory care.
AB  - Understanding of the types and frequency of errors among children in the
      outpatient setting is paramount. The most commonly described errors involve
      medical treatment, communication failures, patient identification, laboratory,
      and diagnostic errors. Research suggests that adverse events and near misses are
      frequent occurrences in ambulatory pediatrics, but relatively little is known
      about the types of errors, risk factors, or effective interventions in this
      setting. This article will review current information on the descriptive
      epidemiology of pediatric outpatient medical errors, established risk factors for
      these errors, effective interventions to enhance reporting and improve safety,
      and future research needs in this area.

PMID- 23116529
TI  - The emerging role of simulation education to achieve patient safety: translating
      deliberate practice and debriefing to save lives.
AB  - Simulation-based educational processes are emerging as key tools for assessing
      and improving patient safety. Multidisciplinary or interprofessional simulation
      training can be used to optimize crew resource management and safe communication
      principles. There is good evidence that simulation training improves self
      confidence, knowledge, and individual and team performance on manikins. Emerging
      evidence supports that procedural simulation, deliberate practice, and debriefing
      can also improve operational performance in clinical settings and can result in
      safer patient and population/system outcomes in selected settings. This article
      highlights emerging evidence that shows how simulation-based interventions and
      education contribute to safer, more efficient systems of care that save lives.

PMID- 23116531
TI  - FDA working to ensure the safety of medical devices used in the pediatric
      population.
AB  - Special initiatives exist in FDA's Center for Devices and Radiological Health
      (CDRH), the Center for Drug Evaluation and Research, and the Center for Biologics
      Evaluation and Research to ensure the safety and effectiveness of medical
      products used in the vulnerable pediatric population. This article focuses on the
      special programs, projects, and special studies implemented by CDRH to ensure
      this safety and effectiveness in devices used in pediatric patients throughout
      the devices' total product life-cycles. Pediatricians play a major role in
      keeping medical devices safe for use in children by reporting device problems to
      FDA.

PMID- 23116532
TI  - Safe Kids Worldwide: preventing unintentional childhood injuries across the
      globe.
AB  - Unintentional injuries are predictable and preventable. Yet every hour, a child
      in the United States dies from an unintentional injury. Globally, the number is
      even more staggering, with nearly 1 million children dying from unintentional
      injuries each year. Motor vehicle-related injuries, burns, drowning, falls,
      suffocation or choking, and poisoning are just a few of the unintentional injury
      risks threatening children. Patient safety requires a three-pronged strategy of
      behavior change, use of safety devices, and improvement of laws and regulations
      to ensure that all children lead healthy and productive lives.

PMID- 23116533
TI  - Safe pediatric care delivery.

PMID- 23116534
TI  - Insulin requirements in late pregnancy in women with type 1 diabetes mellitus: a
      retrospective review.
AB  - Pregnancy in women with type 1 diabetes mellitus (T1DM) is generally associated
      with increased insulin requirements. AIMS: To determine the frequency and
      significance of declining insulin requirements in late gestation in women with
      T1DM. METHODS: We conducted a retrospective review of 54 women seen at our
      institution from 2006 to 2010 with a diagnosis of T1DM pre-pregnancy and
      presentation for antenatal care prior to 28 weeks. Information was collected
      regarding patient demographics, insulin dose and pregnancy outcome. A 15%
      difference in weight-adjusted basal insulin from 30 weeks gestation to delivery
      was considered significant. RESULTS: Five women (9.3%) had a fall of 15% or more
      and 23 (42.5%) had a rise of 15% or more rise in insulin requirements. There were
      fewer neonatal intensive care admissions but more infants with an APGAR <8 at 5
      min in women with a fall in insulin requirements. These differences were not
      evident when the data were re-analysed by quartiles of change. CONCLUSIONS: In
      most women with T1DM, insulin requirements show little change from 30 weeks
      gestation until delivery. Almost 10% of women had a significant fall in insulin
      requirements which did not correlate with adverse neonatal outcome. These results
      require validation in a larger, prospective trial.

PMID- 23116535
TI  - Effects of supervised exercise on lipid profiles and blood pressure control in
      people with type 2 diabetes mellitus: a meta-analysis of randomized controlled
      trials.
AB  - AIMS: Our study's purpose was to perform a systematic review to assess the effect
      of supervised exercise interventions on lipid profiles and blood pressure
      control. METHODS: We searched electronic databases and selected studies that
      evaluated the effect of supervised exercise intervention on cardiovascular risk
      factors in adult people with type 2 diabetes. We used random effect models to
      derive weighted mean differences of exercise on lipid profiles and blood pressure
      control. RESULTS: Forty-two RCTs (2808 subjects) met inclusion criteria and are
      included in our meta-analysis. Structured exercise was associated with a change
      in systolic blood pressure (SBP) of -2.42 mmHg (95% CI, -4.39 to -0.45 mmHg),
      diastolic blood pressure (DBP) of -2.23 mmHg (95% CI, -3.21 to -1.25 mmHg), high
      density lipoprotein cholesterol (HDL-C) of 0.04 mmol/L (95% CI, 0.02-0.07
      mmol/L), and low-density lipoprotein cholesterol (LDL-C) of -0.16 mmol/L (95% CI,
      -0.30 to -0.01 mmol/L). Heterogeneity was partially explained by age, dietary co
      intervention and the duration and intensity of the exercise. CONCLUSIONS:
      Supervised exercise is effective in improving blood pressure control, lowering
      LDL-C, and elevating HDL-C levels in people with diabetes. Physicians should
      recommend exercise for their adult patients with diabetes who can safely do so.

PMID- 23116536
TI  - The impact of the Yom Kippur fast on emergency room visits among people with
      diabetes.
AB  - This retrospective review of an Israeli computerized medical data base assessed
      visits to emergency departments in the 48h following the commencement of the
      Jewish Yom Kippur fast in the years 1999-2009, and showed that fasting does not
      seem to be associated with an increased rate of visits.

PMID- 23116537
TI  - Organic vapor sorption in a high surface area dysprosium(III)-phosphine oxide
      coordination material.
AB  - PCM-16 is a phosphine coordination material comprised of Dy(III) and
      triphenylphosphine oxide, which displays the highest reported CO2 BET surface
      area for a Ln(III) coordination polymer of 1511 m(2) g(-1). PCM-16 also adsorbs
      2.7 wt % H2 and 65.1 wt % O2 at 77 K and 0.97 bar. The adsorption-desorption
      behavior of a series of organic vapors has been studied in PCM-16 to probe the
      nature of certain host-guest interactions in the pores. Aromatic and polar guest
      species showed high uptakes and marked adsorption/desorption hysteresis, while
      aliphatic vapors were less easily adsorbed. The surface area of PCM-16 could be
      increased significantly (to 1814 m(2) g(-1)) via exchange of Me2NH2(+) cations in
      the pores with smaller NH4(+) groups. 

PMID- 23116539
TI  - Understanding of the size control of biocompatible gold nanoparticles in
      millifluidic channels.
AB  - The size control of gold nanoparticles synthesized in surfactant free water with
      a continuous flow mode was elucidated and used to produce higher concentration (3
      mM) of stabilized gold nanoparticles. The originality of the synthesis was to
      finely modulate the initial pH of the reducing agent instead of the gold
      precursor to modify the kinetic of the reaction. The acceleration of the kinetic
      (~1 s) prevents the modification of the gold precursors ensuring the control of
      the final size (from 3 to 25 nm) of the nanoparticles with a low polydispersity
      for aqueous surfactant free solution. The accurate measure of the size
      distribution by small angle X-ray scattering was combined to the use of a model
      based on the coupling of nucleation and growth equations together with a
      progressive injection of monomers. The results on the final state show that the
      size of the nanoparticles is indeed controlled by the kinetic of reduction of
      gold atoms. A millifluidic setup equipped with a homemade mixer offers a robust
      way of rapid mixing to obtain a reproducible production of large amounts of
      nanoparticles.

PMID- 23116540
TI  - Multifaces of neuropeptide Y in the brain--neuroprotection, neurogenesis and
      neuroinflammation.
AB  - Neuropeptide Y (NPY) has been implicated in the modulation of important features
      of neuronal physiology, including calcium homeostasis, neurotransmitter release
      and excitability. Moreover, NPY has been involved as an important modulator of
      hippocampal and thalamic circuits, receiving particular attention as an
      endogenous antiepileptic peptide and as a potential master regulator of feeding
      behavior. NPY not only inhibits excessive glutamate release (decreasing circuitry
      hyperexcitability) but also protects neurons from excitotoxic cell death.
      Furthermore, NPY has been involved in the modulation of the dynamics of dentate
      gyrus and subventricular zone neural stem cell niches. In both regions, NPY is
      part of the chemical resource of the neurogenic niche and acts through NPY Y1
      receptors to promote neuronal differentiation. Interestingly, NPY is also
      considered a neuroimmune messenger. In this review, we highlight recent evidences
      concerning paracrine/autocrine actions of NPY involved in neuroprotection,
      neurogenesis and neuroinflammation. In summary, the three faces of NPY, discussed
      in the present review, may contribute to better understand the dynamics and cell
      fate decision in the brain parenchyma and in restricted areas of neurogenic
      niches, in health and disease.

PMID- 23116538
TI  - Treatment of multiple system atrophy using intravenous immunoglobulin.
AB  - BACKGROUND: Multiple system atrophy (MSA) is a progressive neurodegenerative
      disorder of unknown etiology, manifesting as combination of parkinsonism,
      cerebellar syndrome and dysautonomia. Disease-modifying therapies are
      unavailable. Activation of microglia and production of toxic cytokines suggest a
      role of neuroinflammation in MSA pathogenesis. This pilot clinical trial
      evaluated safety and tolerability of intravenous immunoglobulin (IVIG) in MSA.
      METHODS: This was a single-arm interventional, single-center, open-label pilot
      study. Interventions included monthly infusions of the IVIG preparation
      Privigen(r), dose 0.4 gram/kg, for 6 months. Primary outcome measures evaluated
      safety and secondary outcome measures evaluated preliminary efficacy of IVIG.
      Unified MSA Rating Scale (UMSARS) was measured monthly. Quantitative brain
      imaging using 3T MRI was performed before and after treatment. RESULTS: Nine
      subjects were enrolled, and seven (2 women and 5 men, age range 55-64 years)
      completed the protocol. There were no serious adverse events. Systolic blood
      pressure increased during IVIG infusions (p<0.05). Two participants dropped out
      from the study because of a non-threatening skin rash. The UMSARS-I (activities
      of daily living) and USMARS-II (motor functions) improved significantly post
      treatment. UMSARS-I improved in all subjects (pre-treatment 23.9 +/- 6.0 vs. post
      treatment 19.0+/-5.9 (p=0.01). UMSARS-II improved in 5 subjects, was unchanged in
      1 and worsened in 1 (pre-treatment 26.1+/-7.5 vs. post-treatment 23.3+/-7.3
      (p=0.025). The MR imaging results were not different comparing pre- to post
      treatment. CONCLUSIONS: Treatment with IVIG appears to be safe, feasible and well
      tolerated and may improve functionality in MSA. A larger, placebo-controlled
      study is needed.

PMID- 23116542
TI  - Increased power density from a spiral wound microbial fuel cell.
AB  - Using Microbial fuel cell (MFC) to convert organic and inorganic matter into
      electricity is of great interest for powering portable devices, which is now
      still limited by the output of MFC. In this study, a spiral wound MFC (SWMFC)
      with relatively large volume normalized surface area of separator (4.2 cm(2)/ml)
      was fabricated to enhance power generation. Compared with double-membrane MFC
      (DMMFC) and conventional double chamber MFC (DCMFC), the power density of SWMFC
      increased by 42% and 99% resulted from its lower internal resistance. Besides
      larger separator area, the better performance of SWMFC benefited from its
      structure sandwiching the cathodes between two separators. This point was proved
      again by a comparison of another DCMFC and a triple chamber MFC (TCMFC) as well
      as a simulation using finite element method. Moreover, the feature of SWMFC was
      more convenient and compact to scale up. Therefore, SWMFC provides a promising
      configuration for high power output as a portable power source.

PMID- 23116541
TI  - Cementless modular total hip arthroplasty in patients younger than fifty with
      femoral head osteonecrosis: minimum fifteen-year follow-up.
AB  - This study aimed to report the outcome of total hip arthroplasty (THA) with a
      modular femoral component in patients younger than fifty years with osteonecrosis
      of femoral head. Sixty-four osteonecrotic hips in fifty-five patients were
      available for clinical and radiographic analyses at minimum follow-up of fifteen
      years. The mean Harris hip score improved from 36 points preoperatively to 92.7
      points at final follow-up. Sixty-two (95.3%) hips demonstrated stable bone
      ingrowth. No hips showed loosening or required revision for aseptic loosening.
      Survivorship with an end point of stem revision for any reason was 93.8% and for
      aseptic loosening was 100% at 16.8years. We believe that cementless THA with a
      modular stem is a promising procedure for young and active patients with
      osteonecrosis of the femoral head.

PMID- 23116543
TI  - Layer-by-layer assembly of graphene, Au and poly(toluidine blue O) films sensor
      for evaluation of oxidative stress of tumor cells elicited by hydrogen peroxide.
AB  - High level of oxidative stress is involved in formation of incipient tumor and
      carcinomatous cells. Here in this contribution we have explored a facile strategy
      to assess the oxidative stress elicited by hydrogen peroxide (H(2)O(2)) in cells
      with amperometric current-time technique in vitro. An electrochemical biosensor
      exhibiting high sensitivity and selectivity to H(2)O(2) is fabricated by
      integration of graphene with gold nanoparticles and poly(toluidine blue O) films.
      The efflux of H(2)O(2) from several representative tumor cells and normal cells
      on exposure to ascorbic acid could be detected by using the graphene-based
      nanocomposite films. The results indicate that tumor cells release much more
      H(2)O(2) than do the normal cells. The novel sensor raises the possibility for
      clinical diagnostic application to evaluate the higher level of intracellular
      oxidative stress of tumor cells in comparison with normal cells.

PMID- 23116544
TI  - Improved DNA detection by utilizing electrically neutral DNA probe in field
      effect transistor measurements as evidenced by surface plasmon resonance imaging.
AB  - Intensive efforts have been focused on the development of ultrasensitive DNA
      biosensors capable of quantitative gene expression analysis. Various neutralized
      nucleic acids have been demonstrated as alternative and attractive probe for the
      design of a DNA chip. However, the mechanism of the improvements has not been
      clearly revealed. In this investigation, we used a newly developed neutral
      ethylated DNA (E-DNA), a DNA analog with the "RO-P-O" backbone (wherein R could
      be methyl, ethyl, aryl, or alkyl group) obtained from synthetic procedures, and a
      silicon nanowire (SiNW) field-effect transistor (FET) to evaluate the difference
      in DNA detection performance while using E-DNA and DNA as probes. It is
      demonstrated that using the E-DNA probe in the FET measurement could have a
      significantly enhanced effect upon the detection sensitivity. Surface plasmon
      resonance imaging (SPRi) was used to evidence the mechanism of the improved
      detection sensitivity. SPRi analysis showed the amounts of probe immobilization
      on the sensor surface and the hybridization efficiency were both enhanced with
      the use of E-DNA. Consequently, neutral ethylated DNA probe hold a great promise
      for DNA sensing, especially in the electrical-based sensor.

PMID- 23116545
TI  - Evaluating the performance of fibronectin 1 (FN1), integrin alpha4beta1 (ITGA4),
      syndecan-2 (SDC2), and glycoprotein CD44 as the potential biomarkers of oral
      squamous cell carcinoma (OSCC).
AB  - OBJECTIVES: Some extracellular matrix genes as prognostic biomarkers for oral
      squamous cell carcinoma (OSCC) were evaluated. METHODS: We investigated gene
      expression of fibronectin 1 (FN1), integrin alpha4beta1 (ITGA4), syndecan-2
      (SDC2), and glycoprotein CD44 in matched OSCC/margin tissues. RESULTS: Areas
      under receiver-operating characteristic curves (AUCs) of relative mRNA expression
      of FN1, ITGA4, SDC2, and CD44 were 0.700, 0.677, 0.513, and 0.549, respectively.
      For tongue/mouth floor and edentulous ridge, AUC for FN1 and ITGA4 were 0.827 and
      0.725 and sensitivities/specificities were 80%/84% and 88%/52%, respectively.
      CONCLUSION: FN1 and ITGA4 are potential OSCC biomarkers for tongue/mouth floor
      and edentulous ridge.

PMID- 23116546
TI  - Demographic indicators of trust in federal, state and local government:
      implications for Australian health policy makers.
AB  - OBJECTIVE: To provide baseline findings regarding Australians' trust in federal,
      state and local government. METHODS: A computer-assisted telephone interviewing
      (CATI) survey was administrated during October to December 2009 to a random
      sample (n=1109) across Australia (response rate 41.2%). Binary logistic
      regression analyses were carried out by means of SPSS. RESULTS: Age, household
      size, household income, IRSD and ARIA were found to be significant indicators for
      trust in federal, state and local government. Trust in state government is lower
      for older respondents and respondents living in inner and outer regional areas.
      Trust in local council is lower in respondents living in inner regional areas,
      respondents living in disadvantaged areas, and respondents in the income bracket
      of $60001 to $100000. Trust in federal government is lower for older respondents
      and respondents living in disadvantaged areas. Of note is diminished trust in
      government among older, regional and lower income ($30001-$60000) respondents.
      CONCLUSIONS: Trust in all levels of government was found to be the lowest in
      population groups that are identified by empirical research and media to have the
      poorest access to government services. As a consequence, improved access to
      services for these populations may increase trust in health policy. Increased
      trust in health governance may in turn, ensure effective dissemination and
      implementation of health policies and that existing inequities are not
      perpetuated through distrust of health information and policy initiatives.

PMID- 23116547
TI  - Communication skills training in dementia care: a systematic review of
      effectiveness, training content, and didactic methods in different care settings.
AB  - BACKGROUND: Caring for and caring about people with dementia require specific
      communication skills. Healthcare professionals and family caregivers usually
      receive little training to enable them to meet the communicative needs of people
      with dementia. This review identifies existent interventions to enhance
      communication in dementia care in various care settings. METHODS: We searched
      MEDLINE, AMED, EMBASE, PsychINFO, CINAHL, The Cochrane Library, Gerolit, and Web
      of Science for scientific articles reporting interventions in both English and
      German. An intervention was defined as communication skills training by means of
      face-to-face interaction with the aim of improving basic communicative skills.
      Both professional and family caregivers were included. The effectiveness of such
      training was analyzed. Different types of training were defined. Didactic
      methods, training content, and additional organizational features were
      qualitatively examined. RESULTS: This review included 12 trials totaling 831
      persons with dementia, 519 professional caregivers, and 162 family caregivers.
      Most studies were carried out in the USA, the UK, and Germany. Eight studies took
      place in nursing homes; four studies were located in a home-care setting. No
      studies could be found in an acute-care setting. We provide a list of basic
      communicative principles for good communication in dementia care. Didactic
      methods included lectures, hands-on training, group discussions, and role-play.
      CONCLUSION: This review shows that communication skills training in dementia care
      significantly improves the quality of life and wellbeing of people with dementia
      and increases positive interactions in various care settings. Communication
      skills training shows significant impact on professional and family caregivers'
      communication skills, competencies, and knowledge. Additional organizational
      features improve the sustainability of communication interventions.

PMID- 23116548
TI  - High-mobility group box family of proteins: ligand and sensor for innate
      immunity.
AB  - Recent discoveries in signal-transducing innate receptors have illustrated the
      close link between innate and adaptive immunity. These advances revisit a
      fundamental issue of immunology, the recognition of self and non-self molecules
      by the immune system. Indeed, mounting evidence has been provided that the
      sensing of self-derived molecules by the immune system is important for health
      and disease. The high-mobility group box (HMGB) proteins, particularly HMGB1, are
      self-derived immune activators that have multiple functions in the regulation of
      immunity and inflammation. In this review, we summarize current knowledge of the
      function of HMGB proteins, as a ligand that can evoke inflammatory responses, and
      as a sensor for nucleic-acid-mediated immune responses.

PMID- 23116549
TI  - Communication between pathogenic T cells and myeloid cells in neuroinflammatory
      disease.
AB  - Clinical and experimental data suggest that T helper (TH) cells are involved in
      the pathogenicity of experimental autoimmune encephalomyelitis (EAE) and multiple
      sclerosis (MS), but it is unlikely that they are directly responsible for the
      observed demyelination and axonal loss. Instead, the cell population that targets
      the destruction of oligodendrocytes and axons, and the mechanism exploited by
      central nervous system (CNS)-invading encephalitogenic TH cells to instruct these
      cells to mediate tissue damage, are still under debate. Mature myeloid cells form
      a prominent component of the neuroinflammatory infiltrates and are the suspected
      culprits behind the CNS injury due to their arsenal of toxic factors. Here, we
      describe the process of encephalitogenic TH cell activation followed by their
      entry into the CNS and discuss how pathogenic TH cells influence the myeloid
      compartment.

PMID- 23116550
TI  - Drug targets in the cytokine universe for autoimmune disease.
AB  - In autoimmune disease, a network of diverse cytokines is produced in association
      with disease susceptibility to constitute the 'cytokine milieu' that drives
      chronic inflammation. It remains elusive how cytokines interact in such a complex
      network to sustain inflammation in autoimmune disease. This has presented huge
      challenges for successful drug discovery because it has been difficult to predict
      how individual cytokine-targeted therapy would work. Here, we combine the
      principles of Chinese Taoism philosophy and modern bioinformatics tools to
      dissect multiple layers of arbitrary cytokine interactions into discernible
      interfaces and connectivity maps to predict movements in the cytokine network.
      The key principles presented here have important implications in our
      understanding of cytokine interactions and development of effective cytokine
      targeted therapies for autoimmune disorders.

PMID- 23116551
TI  - Options to meet the future global demand of radionuclides for radionuclide
      therapy.
AB  - Nuclear medicine continues to represent one of the important modalities for
      cancer management. While diagnostic nuclear medicine for cancer management is
      fairly well established, therapeutic strategies using radionuclides are yet to be
      utilized to their full potential. Even if 1% of the patients undergoing
      diagnostic nuclear medicine procedures can benefit from subsequent nuclear
      therapeutic intervention, the radionuclide requirement for nuclear therapeutics
      would be expected to be in the multi-million Curie levels. Meeting the demand for
      such high levels of therapeutic radionuclides at an affordable price is an
      important task for the success of radionuclide therapy. Although different types
      of particle emitters (beta, alpha, Auger electron etc.) have been evaluated for
      treating a wide variety of diseases, the use of beta- emitting radionuclides is
      most feasible owing to their ease of production and availability. Several beta-
      emitting radionuclides have been successfully used to treat different kind of
      diseases. However, many of these radionuclides are not suitable to meet the
      projected demand owing to the non-availability with sufficiently high specific
      activity and adequate quantity because of high production costs, relatively short
      half-lives etc. This article describes the advantages and disadvantages for
      broader uses of some of the well known therapeutic radionuclides. In addition,
      radioisotopes which are expected to have the potential to meet the growing demand
      of therapeutic radionuclides are also discussed.

PMID- 23116552
TI  - Comparison between two treatment planning systems for volumetric modulated arc
      therapy optimization for prostate cancer.
AB  - PURPOSE: To investigate the performances of two commercial treatment planning
      systems (TPS) for Volumetric Modulated Arc Therapy (VMAT) optimization regarding
      prostate cancer. The TPS were compared in terms of dose distributions, treatment
      delivery parameters and quality control results. MATERIALS AND METHODS: For ten
      patients, two VMAT plans were generated: one with Monaco TPS (Elekta) and one
      with Pinnacle TPS (Philips Medical Systems). The total prescribed dose was 78 Gy
      delivered in one 360 degrees  arc with a Synergy((r)) linear accelerator equipped
      with a MLCi2((r)). RESULTS: VMAT with Monaco provided better homogeneity and
      conformity indexes but lower mean dose to PTVs than Pinnacle. For the bladder
      wall (p = 0.019), the femoral heads (p = 0.017), and healthy tissues (p = 0.005),
      significantly lower mean doses were found using Monaco. For the rectal wall, VMAT
      with Pinnacle provided a significantly (p = 0.047) lower mean dose, and lower
      dose into 50% of the volume (p = 0.047) compared to Monaco. Despite a greater
      number of monitor units (factor 1.5) for Monaco TPS, the total treatment time was
      equivalent to that of Pinnacle. The treatment delivery parameter analysis showed
      larger mean MLC area for Pinnacle and lower mean dose rate compared to Monaco.
      The quality control results gave a high passing rate (>97.4%) for the gamma index
      for both TPS but Monaco provided slightly better results. CONCLUSION: For
      prostate cancer patients, VMAT treatment plans obtained with Monaco and Pinnacle
      offered clinically acceptable dose distributions. Further investigations are in
      progress to confirm the performances of the two TPS for irradiating more complex
      volumes.

PMID- 23116554
TI  - [A rare cause of haemoptysis in adolescence].

PMID- 23116553
TI  - Correlation of aldo-ketoreductase (AKR) 1C3 genetic variant with doxorubicin
      pharmacodynamics in Asian breast cancer patients.
AB  - AIMS: Aldo-ketoreductases have been implicated in the metabolism of doxorubicin.
      We sought to assess the influence of AKR1C3 genetic variants on doxorubicin
      metabolism. METHODS: We sequenced AKR1C3 exon 5 and genotyped seven functional
      single nucleotide polymorphisms in CBR3, ABCB1 and SLC22A16 involved in
      doxorubicin pharmacology in 151 Asian breast cancer patients treated with
      doxorubicin-containing chemotherapy, and correlated these genotypes with
      doxorubicin pharmacokinetics and pharmacodynamics. RESULTS: Two previously
      reported AKR1C3 intronic variants, IVS4-212 C>G and IVS4+218 G>A, were detected.
      The AKR1C3 IVS4-212 GG genotype was associated with significantly lower cycle 1
      day 15 leucocyte (mean leucocytes 2.49 +/- 1.57 * 10(9) vs. 3.85 +/- 3.42 * 10(9)
      l(-1) , P = 0.007) and neutrophil counts (mean neutrophils 0.70 +/- 1.01 * 10(9)
      vs. 1.56 +/- 2.80 * 10(9) l(-1) , P = 0.008) and significant improvement of
      progression-free survival [PFS, mean PFS 49.0 (95% confidence interval 42.2-55.8)
      vs. 31.0 (95% confidence interval 20.7-41.2) months, P = 0.017] and overall
      survival [OS; mean OS 64.4 (95% confidence interval 58.3-70.5) vs. 46.3 (95%
      confidence interval 35.1-57.5) months, P = 0.006] compared with those carrying at
      least one C allele. There was no significant association between AKR1C3 IVS4-212
      C>G and doxorubicin pharmacokinetics. Of the other seven single nucleotide
      polymorphisms genotyped, CBR3 G11A correlated with doxorubicinol area under the
      concentration-time curve and OS, ABCB1 G2677T/A correlated with doxorubicin
      clearance and platelet toxicity, while ABCB1 IVS26+59 T>G correlated with OS. The
      AKR1C3 IVS4-212 C<G genotype remained significantly correlated with both PFS and
      OS on multivariate analysis with clinical prognosticators. CONCLUSIONS: The
      AKR1C3 IVS4-212 GG genotype was associated with greater haematological toxicity
      and longer progression-free survival and overall survival after doxorubicin-based
      therapy, suggesting potential interaction of this variant with doxorubicin
      metabolism.

PMID- 23116555
TI  - [Intra-abdominal focal fat necrosis].

PMID- 23116556
TI  - In vitro antibacterial, antifungal and cytotoxic activities of some triazole
      Schiff bases and their oxovanadium(IV) complexes.
AB  - The condensation reaction of 3,5-diamino-1,2,4-triazole with methoxy-, chloro-,
      bromo-, iodo- and nitro-substituted 2-hydroxybenzaldehydes formed triazole Schiff
      bases (L(1))-(L(6)). The synthesized ligands have been characterized through
      physical, spectral and analytical data. Furthermore, the reaction of synthesized
      Schiff bases with the oxovanadium(IV) sulphate in (1:2) (metal:ligand) molar
      ratio afforded the oxovanadium(IV) complexes (1)-(6). All the complexes were non
      electrolytic and showed a square-pyramidal geometry. The synthesized compounds
      have been screened for in-vitro antibacterial, antifungal and brine shrimp
      bioassay. The bioactivity data showed the complexes to be more active than the
      original Schiff bases. 

PMID- 23116557
TI  - Structural analysis of ATP analogues compatible with kinase-catalyzed labeling.
AB  - Kinase-catalyzed protein phosphorylation is an important biochemical process
      involved in cellular functions. We recently discovered that kinases promiscuously
      accept gamma-modified ATP analogues as cosubstrates and used several ATP
      analogues as tools for studying protein phosphorylation. Herein, we explore the
      structural requirements of gamma-modified ATP analogues for kinase compatibility.
      To understand the influence of linker length and composition, a series of ATP
      analogues was synthesized, and the efficiency of kinase-catalyzed labeling was
      determined by quantitative mass spectrometry. This study on factors influencing
      kinase cosubstrate promiscuity will enable design of ATP analogues for a variety
      of kinase-catalyzed labeling reactions.

PMID- 23116558
TI  - Constructing a framework for quality activity in primary care.
AB  - INTRODUCTION: In 2009, the Royal New Zealand College of General Practitioners
      commissioned the development of a framework to facilitate quality-improvement
      activity in primary care settings. This paper outlines the development of the
      framework, which integrates concepts of quality with the reality of practice
      based clinical care, and discusses its value for primary care quality
      improvement. METHOD: Framework development involved: (1) literature review of
      theoretical approaches to healthcare quality; (2) field work utilising a mixed
      methods approach to obtain empirical data; and (3) model design. RESULTS: Primary
      care practitioners are juggling competing priorities. Models and tools that
      promote quality-related activity at practice level need to take into account, and
      incorporate by design, day-to-day clinical and practice functions. CONCLUSIONS:
      The quality framework identifies the components of primary care practice and
      locates this model within the concepts and activities necessary for quality
      improvement. It may be used by primary care organisations and practices to
      facilitate focussed quality-improvement activity and self-directed process
      review. The framework was developed for, and within a New Zealand primary care
      setting, and is applicable internationally and within other healthcare settings.

PMID- 23116559
TI  - Anesthesia and Alzheimer's disease: time to wake up!

PMID- 23116560
TI  - Combination of glibenclamide-metformin HCl for the treatment of type 2 diabetes
      mellitus.
AB  - INTRODUCTION: Combination of glibenclamide (glyburide in the U.S.) and metformin
      hydrochloride simultaneously addresses two different but complimentary mechanisms
      to improve glycemic control in type 2 diabetes. AREAS COVERED: The
      pharmacokinetics, efficacy, and side effect profile of the oral combination of
      glibenclamide-metformin are reviewed. EXPERT OPINION: Those patients,
      uncontrolled with single oral agent sulfonylurea or metformin alone, benefit from
      combination glibenclamide-metformin. There is improvement in fasting plasma
      glucose, HbA(1C), and post-prandial glucose control, and patients are more likely
      to achieve a HbA(1C) < 7%. Initiation should be started at the lowest doses and
      titrated to get the desired effect. Combination therapy allows for reduced pill
      burden while treating a multifactorial disease by two different mechanisms.
      Practitioners should be cognizant of risks of hypoglycemia and the theoretical
      potential for lactic acidosis in the elderly and those with renal impairment. We
      caution the use of glibenclamide-metformin in patients at risk for cardiovascular
      disease. Therapy should be individualized, but overall, combination of
      glibenclamide-metformin should be considered in patients, without renal or
      cardiovascular impairment, who are not controlled on monotherapy alone.
      Alternatively, practitioners may want to weigh the efficacy and safety of
      available dipeptidyl-peptidase-4 inhibitor-metformin combinations to those of
      glibenclamide-metformin when considering combination therapy.

PMID- 23116561
TI  - Investigating obstructive sleep apnoea: will the health system have the capacity
      to cope? A population study.
AB  - OBJECTIVE: To obtain prevalence estimates of clinical features of obstructive
      sleep apnoea (OSA) and identify the dimensions of the public health problem
      requiring further investigation for an Australian population. METHODS: The South
      Australian Health Omnibus Survey is an annual representative population survey of
      South Australians aged>=15 years, conducted via interviewer-administered
      questionnaire. In 2009, 3007 participants were asked the STOP-BANG instrument
      measure of obstructive sleep apnoea risk, which includes symptoms of loud
      snoring, frequent tiredness during daytime, observed apnoea, and high blood
      pressure (STOP), and measured body mass index, age, neck circumference and gender
      (BANG). Three or more positive response categorises a person at high risk for
      OSA. RESULTS: Snoring was reported by 49.7% of adults. Tiredness after sleep more
      than 3 - 4 times per week was reported by 24.8%, and during wake-time by 27.7% of
      adults, with 8.8% reporting having fallen asleep while driving. Over half of the
      surveyed men (57.1%, n=566) and 19.3% (n=269) of the women were classified at
      high-risk of OSA with the STOP-BANG measure. In multivariable models, high risk
      was associated with less education, lower income, and residence in a regional
      rather than metropolitan area. CONCLUSION: The high prevalence of adults at risk
      for OSA suggests that the capacity currently available within the healthcare
      system to investigate and diagnose OSA is likely to be inadequate, particularly
      outside urban areas. This highlights an important public health problem that
      requires further detailed study and trials of new models of care.

PMID- 23116564
TI  - Characterization of a spontaneously immortalized bovine trabecular meshwork cell
      line.
AB  - Trabecular meshwork (TM) cells have widely been used as an in vitro model for
      glaucoma research. However, primary TM cells suffer the disadvantages of limited
      cell numbers and slow rates of proliferation. We discovered a spontaneously
      transformed bovine TM (BTM) cell line, BTM-28T. This cell line proliferated
      rapidly in low-glucose culture medium but also demonstrated contact inhibition in
      high-glucose culture medium. BTM-28T cells expressed key TM cell markers
      including alpha-smooth muscle actin (alpha-SMA), laminin and collagen IV (col
      IV). Also, 100 nM dexamethasone (DEX) enhanced the formation of cross-linked
      actin networks (CLANs) in confluent BTM-28T cell cultures. Transforming growth
      factor beta 2 (TGFbeta2) induced the expression of fibronectin (FN), plasminogen
      activator inhibitor-1 (PAI-1), and connective tissue growth factor (CTGF) in our
      cell cultures. This cell line will be helpful to better understand the aqueous
      humor outflow pathway as related to the pathophysiology of glaucoma.

PMID- 23116563
TI  - An MIP/AQP0 mutation with impaired trafficking and function underlies an
      autosomal dominant congenital lamellar cataract.
AB  - Autosomal dominant congenital cataracts have been associated with mutations of
      genes encoding several soluble and membrane proteins. By candidate gene
      screening, we identified a novel mutation in MIP (c.494 G > A) that segregates
      with a congenital lamellar cataract within a south Indian family and causes the
      replacement of a highly conserved glycine by aspartate (G165D) within aquaporin0
      (AQP0). Unlike wild type AQP0, expression of AQP0-G165D in Xenopus oocytes did
      not facilitate swelling in hypotonic medium. In transfected HeLa cells, wild type
      AQP0 localized at the plasma membrane while AQP0-G165D was retained within the
      secretory pathway, and localized mainly within the endoplasmic reticulum. These
      results suggest that mutation of this conserved glycine residue leads to improper
      trafficking of AQP0-G165D and loss of water channel function. They emphasize the
      importance of AQP0 for maintenance of lens transparency and identify a critical
      residue that is conserved among aquaporins, but has not previously been
      associated with disease-associated replacement.

PMID- 23116562
TI  - Mitochondrial localization of P-glycoprotein and peptide transporters in corneal
      epithelial cells--novel strategies for intracellular drug targeting.
AB  - This study was designed to investigate functional localization of both efflux (P
      glycoprotein, P-gp) and influx (peptide) transporters in the mitochondrial
      membrane of cultured rabbit primary corneal epithelial cells (rPCECs). Isolation
      and purification of mitochondria was performed by optimized cell fractionation
      method. Mitochondrial integrity was measured by JC-1 uptake experiment. The
      efflux activity of P-gp was assessed by performing in vitro uptake studies on
      isolated mitochondria with Rhodamine 123 (Rho-123) alone and in the presence of P
      gp inhibitors (quinidine and cyclosporine A) using fluorimetry and flow cytometry
      analysis. Functional activity of peptide transporter was assessed by performing
      in vitro uptake studies of [3H] Gly-sar on isolated mitochondria in the presence
      or absence of peptide transporter substrate (Val-Val). Molecular characterization
      of P-gp and peptide transporter was assessed by western blot and confocal
      analysis. Enhanced JC-1 accumulation in the isolated fraction confirmed
      mitochondrial membrane integrity. Significantly higher uptake of Rho-123 on
      isolated mitochondria was observed in the presence of quinidine (75 and 100 MUM)
      and cyclosporine A (10 MUM). Significantly lower uptake of [3H] Gly-sar was
      observed in the presence of val-val due to competitive inhibition of peptide
      transporter on isolated mitochondria. Western blot and confocal analysis further
      confirmed the presence of P-gp and peptide transporter on the mitochondrial
      membrane of rPCECs. The present study demonstrates the functional and molecular
      characterization of P-gp and peptide transporters in the mitochondrial membranes
      of rPCECs. This knowledge of mitochondrial existence of P-gp and peptide
      transporter will aid in the development of subcellular ocular drug delivery
      strategies.

PMID- 23116565
TI  - Self-practice and self-reflection in cognitive behaviour therapy training: what
      factors influence trainees' engagement and experience of benefit?
AB  - BACKGROUND: Previous studies of self-practice/self-reflection (SP/SR) CBT
      training have found that trainees report significant benefits from practising CBT
      techniques on themselves (self-practice) and reflecting on their experience (self
      reflection) as a formal part of their CBT training. However, not all trainees
      experience the same level of benefit from SP/SR and not all types of training
      course produce benefits to the same extent. AIMS: This paper examines the
      question: What factors influence trainees' reported benefit from SP/SR? The aim
      was to develop a model to maximize the value of SP/SR training. METHOD: The
      authors used a grounded theory analysis of four SP/SR training courses, varying
      along several dimensions, to derive a model that could account for the data.
      RESULTS: A model was derived comprising of seven elements: Two outcomes -
      "Experience of Benefit" and "Engagement with the Process" - that mutually
      influence one another; and five other influencing factors - "Course Structure and
      Requirements", "Expectation of Benefit", "Feeling of Safety with the Process",
      "Group Process", and "Available Personal Resources" - that mediate the impact on
      Engagement with the Process and Experience of Benefit from SP/SR. CONCLUSIONS: A
      model that provides guidance about the best ways to set up and develop SP/SR
      programs has been developed. This model may now be subject to empirical testing
      by trainers and researchers. Implications and recommendations for the design and
      development of future SP/SR programs are discussed.

PMID- 23116566
TI  - Resource barriers to the facilitation of organ and tissue donation reported by
      Australian emergency clinicians.
AB  - OBJECTIVE: To explore emergency department clinicians' perceived resource
      barriers to facilitating organ and tissue donation (OTD). METHODS: A cross
      sectional national online survey of Australian emergency department (ED)
      clinicians. RESULTS: ED clinicians reported a range of resource barriers that
      hinder the facilitation of OTD, most notably a lack of time to discuss OTD with a
      patient's family (74.6%). Those reporting more resource barriers had been less
      involved in OTD-related tasks. For example, those reporting a lack of time to
      assess a patient's suitability to be a potential donor had less experience with
      OTD-related tasks in the last calendar year than did those who reported that they
      often or always have enough time for this (P<0.01). In addition, ED clinicians
      working in DonateLife network hospitals were more involved in OTD-related tasks
      (P<0.01) and reported fewer resource shortages in the ED and the hospital
      overall. CONCLUSIONS: Resource shortages hinder the facilitation of OTD in the ED
      and are related to decreased involvement in OTD-related tasks. In addition, ED
      clinicians working in DonateLife hospitals are more involved in OTD-related tasks
      and report fewer resource shortages overall. Addressing resource shortages and
      extending the DonateLife network could benefit OTD rates initiated from the ED.

PMID- 23116567
TI  - Enhanced MK-801-induced locomotion in Kir6.2 knockout mice.
AB  - ATP-sensitive K(+) (K-ATP) channels provide a unique link between cellular
      energetics and electrical excitability, and also act as a unifying molecular
      coordinator of the body's response to stress. Although the body's response to
      stress is implicated in the worsening or relapse of psychotic symptoms in
      schizophrenia, the role of K-ATP channels remains unclear. Therefore, the aim of
      the current study was to investigated the effect of K-ATP channels on
      schizophrenia-like symptoms induced by MK-801 using Kir6.2 (one pore-forming
      subunit of K-ATP) knockout mice. We demonstrated that Kir6.2 knockout enhanced
      locomotor activity significantly compared to the wild-type mice after MK-801
      administration. Moreover, we found that depletion of Kir6.2 significantly
      increased the numbers of Arc-positive cells in cortex, hippocampus and striatum
      in basal state. MK-801 augmented the Arc expression in wild-type mice.
      Collectively, our findings in this study indicate that K-ATP channels are
      involved in the regulation of MK-801-induced acute symptoms of schizophrenia,
      which is associated with the neural excitability. In addition, our results may
      provide valuable information for the development of new treatments for
      schizophrenia.

PMID- 23116568
TI  - Iontophoretic application of an A-type potassium channel blocker to the
      trigeminal ganglion neurons enhances the excitability of Adelta- and C-neurons
      innervating the temporomandibular joint in rats.
AB  - The present study tested the hypothesis that under in vivo conditions the
      iontophoretic application of a I(A) channel blocker, 4-aminopyridine (4-AP), to
      the TRG neurons changes the properties of Adelta-/C-TRG neurons that innervate
      the temporomandibular joint (TMJ) region, using extracellular
      electrophysiological recording with multi-barrel electrodes in pentobarbital
      anesthetized rats. A total of twenty-one neurons (Adelta-: 76%; C-: 24%)
      responded to electrical stimulation of the TMJ region in pentobarbital
      anesthetized rats. TMJ electrical stimulation-induced discharges of Adelta/C
      neurons were significantly potentiated in current dependent manner (30-70 nA) by
      iontophoretic application of 4-AP into the TRGs. The spontaneous firing rates of
      Adelta- and C-neurons were also increased by 4-AP in a current-dependent manner
      (30-70 nA). The mean threshold current that evoked spontaneous discharges of C
      neurons was significantly lower than that of Adelta-neurons. Moreover, the mean
      relative threshold current for electrical stimulation of TMJ-induced response of
      C-TRG neurons was significantly lower than that of Adelta-neuron. The relative
      firing rate of C-neurons induced by 4-AP-treatment (70 nA) was significantly
      higher than for Adelta-neurons. These results suggest that the application of 4
      AP enhanced Adelta/C-TRG neuronal activities innervating the TMJ in vivo and C
      neurons had significantly higher sensitivity for 4-AP than Adelta-neurons.

PMID- 23116569
TI  - Lesion of the cerebellar paravermis increases dopamine D1 receptor levels in the
      contralateral striatum.
AB  - Anatomical and biochemical findings have long suggested that a projection from
      the cerebellum to the basal ganglia exists, and recent findings proposed that the
      cerebellum influences glutamatergic striatal activity. We have previously shown
      that a complete, genetic, lack of Purkinje cells induces an upregulation of
      dopamine D1 receptors (DRD1) in the output of the basal ganglia, the substantia
      nigra pars reticulata. In this study, we produced a focal unilateral lesion in
      the cerebellar paravermal cortex and we studied the levels and distribution of
      dopamine receptors and transporters, with the use of in vitro receptor
      autoradiography. The lesion produced a statistically significant increase in DRD1
      specific binding in the contralateral medial striatum and a bilateral decrease in
      dopamine transporter (DAT) levels in the dorsolateral striatum. Our finding of a
      DRD1 increase after disruption of the cerebellar corticonuclear projection
      suggests that the cerebellar output modulates the basal ganglia DRD1-mediated
      pathway.

PMID- 23116571
TI  - Women's experience of domiciliary postnatal care in Victoria and South Australia:
      a population-based survey.
AB  - OBJECTIVE: Despite the expansion of postnatal domiciliary services, we know
      little about the women receiving visits and how they regard their care. The aim
      of this study is to examine the provision of postnatal domiciliary care from a
      consumer perspective. METHODS: All women who gave birth in September-October 2007
      in South Australia and Victoria were mailed questionnaires 6 months after the
      birth. Women were asked if they had received a midwifery home visit, and to rate
      the care they received. RESULTS: More women in South Australia reported receiving
      a domiciliary visit than in Victoria (88.0% v. 76.0%) and they were more likely
      to rate their care as 'very good' (69.1% v. 63.4%). Younger women, women on a
      lower income, who were holding a healthcare concession card or who had not
      completed secondary education were less likely to receive a visit. CONCLUSION:
      Although the majority of women in public maternity care in Victoria and South
      Australia receive domiciliary care and rate it positively, there are significant
      state-based differences. Those more likely to benefit from domiciliary care are
      less likely to receive a visit. There is a need to further explore the purpose,
      aims and content of domiciliary care at individual and state-wide levels.

PMID- 23116574
TI  - New insights into the pathogenesis, diagnosis, and management of mastocytosis.
AB  - This review describes developments in understanding normal mast cell function and
      genetic changes that predispose to malignant transformation to mastocytosis. Most
      mastocytosis cases are associated with somatically acquired activating mutations
      in the KIT receptor. The role these mutations play in the development of
      mastocytosis is discussed. Mastocytosis is classified into cutaneous mastocytosis
      and systemic mastocytosis. The classification of mastocytosis and clinical
      presentation of each variant is detailed in this report. Progress has been made
      in developing drugs that target the wild-type and mutated KIT receptor, and these
      and other new therapeutic strategies for the treatment of mastocytosis are
      reviewed.

PMID- 23116570
TI  - An investigation of executive functioning, attention and working memory in
      compulsive hoarding.
AB  - BACKGROUND: Compulsive Hoarding involves the acquisition of, and failure to
      discard, a large number of possessions that appear to be useless or of limited
      value, cluttered living spaces and significant distress or impairment in
      functioning (Frost and Hartl, 1996). The problem is multifaceted and appears best
      explained by a cognitive-behavioural framework. AIMS: This study set out to test
      one aspect of Frost and Hartl's (1996) cognitive-behavioural model of compulsive
      hoarding by investigating theorized cognitive deficits in executive functioning,
      such as working memory and attention. METHOD: 24 participants with compulsive
      hoarding were tested on the Digit Span, Spatial Span and the Wisconsin Card
      Sorting Tests (WCST). RESULTS: On theWCST, the hoarding group had a significantly
      higher number of perseveration errors (t=1.67, p=.005) and significantly lower
      numbers of categories completed (t=-2.47, p=.001) than test norms. Only "failure
      to maintain set" was significantly correlated with hoarding severity (r=.435,
      p<.05). CONCLUSIONS: These findings lend support to the theory that people who
      compulsively hoard have executive dysfunction, which impacts on their ability to
      process information. Deficits relate to difficulties in forming effective
      strategies, inadequate feedback response, problems in concept formation, and
      impulsivity. Difficulties in sustained attention also appeared to be a factor in
      hoarding severity. These findings are important in directing more targeted
      clinical interventions.

PMID- 23116575
TI  - Epidemiology and management of uveal melanoma.
AB  - Uveal melanoma is the most common primary intraocular malignancy in adults. The
      disease overwhelmingly affects white populations. Other risk factors include fair
      skin, light iris color, ancestry from northern latitudes, and ocular/oculodermal
      melanocytosis. Historically, enucleation was the definitive treatment of uveal
      melanoma, but brachytherapy and proton beam irradiation are now the most commonly
      used treatment methods. However, there are still no effective therapies against
      metastatic uveal melanoma, which is almost always fatal. Continued advances in
      understanding of the molecular mechanisms of uveal melanoma will facilitate the
      identification of prognostic markers and therapeutic targets.

PMID- 23116573
TI  - What is a Rare Cancer?
AB  - Many rare cancers are essentially an enigma, with little to no information in the
      medical literature. Defining a rare cancer is not as easy as it might seem. As a
      guide, generally an incidence of fewer than 6/100,000 is considered rare. Much of
      the research regarding rare diseases is in its infancy.

PMID- 23116572
TI  - [Laryngeal leishmaniasis. A case report].

PMID- 23116576
TI  - Esthesioneuroblastoma: a contemporary review of diagnosis and management.
AB  - Esthesioneuroblastoma (ENB) is a rare malignancy, representing only 3% to 6% of
      all sinonasal malignancies. A wide array of treatment options for ENB have been
      described in the literature, but prospective clinical trials are absent given the
      tumor's rarity and natural history. Delay in diagnosis leading to an initial
      advanced stage of presentation is common secondary to the clinically hidden
      primary site at the anterior skull base. This article presents data from the
      current body of literature and reviews the advocated roles for surgery, radiation
      therapy and chemotherapy.

PMID- 23116578
TI  - Parathyroid carcinoma: challenges in diagnosis and treatment.
AB  - Parathyroid carcinoma is a malignant neoplasm affecting 0.5% to 5.0% of all
      patients with primary hyperparathyroidism. Since it was first described by De
      Quervain in 1904 to this day, it continues to defy diagnosis and treatment
      because of its rarity, overlapping features with benign parathyroid disease, and
      lack of distinct characteristics. En bloc surgical extirpation of the tumor with
      clear margins remains the best curative treatment. Although prolonged survival is
      possible with recurrent or metastatic disease, cure is rarely achievable.
      Efficacy of adjuvant therapies, such as radiotherapy and chemotherapy, in
      management of persistent, recurrent, or metastatic disease has been
      disappointing.

PMID- 23116577
TI  - Synovial cell sarcoma of the larynx.
AB  - Synovial cell sarcoma represents a rare group of cancers, particularly in the
      head and neck region, that typically affects young individuals and has a male
      preponderance. Prognosis varies with patient age, site and size of the
      malignancy, degree of necrosis, high level of mitotic activity, and neurovascular
      invasion. Complete surgical resection of the tumor via partial or total
      laryngectomy is the first-line treatment in locally invasive disease. CO(2)
      lasers have been shown to be useful in controlling localized disease. There is
      also a role for adjuvant radiotherapy. Ifosfamide-based chemotherapy is most
      useful for malignant disease.

PMID- 23116580
TI  - Neoplasms of the appendix: current treatment guidelines.
AB  - The purpose of this article is to update the medical community on the current
      management of patients with appendiceal neoplasms. The authors discuss clinical
      evidence of medical and surgical treatment with emphasis on presentation,
      diagnosis, pathology, and surgical technique. Current available clinical evidence
      on the use of systemic chemotherapy is included. The authors describe in detail
      management of peritoneal carcinomatosis arising from tumors of the appendix with
      cytoreductive surgery and hyperthermic intraperitoneal therapy as standard of
      care.

PMID- 23116579
TI  - Gastrointestinal stromal tumor--background, pathology, treatment.
AB  - Gastrointestinal stromal tumor (GIST) represents the most common mesechymal tumor
      of the gastrointestinal tract. Discovery of the relationship between unregulated
      KIT kinase and GIST transformation has led to diagnostic and therapeutic
      targeting. Imatinib is the recommended first-line treatment of metastatic GIST.
      In addition, the combination of surgery and imatinib for primary GIST is
      indicated in the adjuvant setting of high-risk patients and there may be benefit
      for this combination in the neoadjuvant setting. The success of molecular
      targeted therapy in GIST represents an important and exciting advance in solid
      tumor oncology.

PMID- 23116584
TI  - Hematology/Oncology Clinics of North America. Rare cancers. Preface.

PMID- 23116581
TI  - Urethral cancer.
AB  - Urethral carcinoma is a rare tumor with predominantly poor survival. Both the
      disease and its treatment can affect both sexual and urinary function. The
      natural history of urethral carcinoma varies, therefore the appropriate
      application of surgery, radiation, and chemotherapy remain unknown. Management of
      this disease remains driven by individual clinician experience and data derived
      from small case series. This article discusses the histology and anatomy of the
      male and female urethra, as well as their natural history. In addition, the
      epidemiology, clinical presentation, diagnosis, staging, treatment, and future
      directions of management of cancer arising in the urethra are addressed.

PMID- 23116583
TI  - Merkel cell carcinoma.
AB  - Merkel cell carcinoma (MCC) is a rare but aggressive carcinoma of the skin,
      arising most commonly in sun-exposed sites of elderly patients. The diagnosis is
      based on characteristic histopathologic features. In 2008, the discovery of the
      Merkel cell polyomavirus led to intensified research into the viral
      pathogenesisis of MCC. MCC staging guidelines were established in 2010, and it
      demonstrated the importance of distinguishing clinical vs. pathologic evaluation
      of lymph nodes in MCC. Surgery and/or radiation is of the mainstay of therapy for
      early disease, while chemotherapy is reserved for more advanced disease.
      Treatments based on immunologic mechanisms are currently in development.

PMID- 23116582
TI  - Current treatment of anal squamous cell carcinoma.
AB  - The primary aim of anal cancer treatment is loco-regional control with
      preservation of anal function. Phase III trials consistently demonstrate
      radiotherapy with concurrent 5FU and mitomycin (MMC) chemoradiation is the
      standard of care for anal cancer. Salvage surgery is associated with considerable
      morbidity and requires specialised input. With current sophisticated radiological
      staging and the ability to spare critical normal tissues with intensity-modulated
      radiotherapy, a "one-size-fits-all" approach is probably inappropriate.
      Radiotherapy dose-escalation and intensification of the concurrent chemotherapy
      might improve local control, but may also adversely affect colostomy-free
      survival. Integration of biologic therapy with conventional chemotherapies looks
      hopeful in the future.

PMID- 23116586
TI  - The expression of a putative exotoxin and an ABC transporter during bovine
      intramammary infection contributes to the virulence of Staphylococcus aureus.
AB  - Staphylococcus aureus is a leading cause of intramammary infections (IMI) and
      bovine mastitis is an important disease for the dairy industry. As this bacterium
      probably expresses specific genes for establishment of IMI, we studied the
      transcriptional profile of four S. aureus strains recovered from experimentally
      infected cows. Microbial RNA was extracted from bacteria isolated from milk,
      reverse-transcribed and labeled for hybridization to sub-genomic microarrays to
      detect candidate genes for further investigations. Several S. aureus genes were
      expressed during IMI; some were detected in samples from more than one strain,
      more than one cow and at more than one time point during infection. A selection
      of four genes showing strong expression and with putative functions in
      pathogenesis was further studied by qPCR. By comparing the expression in
      different media in vitro, we found that gene SACOL2171 was induced by iron
      restriction whereas the expression of the transcriptional regulator SACOL2325 and
      the ABC transporter SACOL0718-720 (vraFG) were induced by milk. In addition, the
      putative exotoxin SACOL0442 seemed to require the intramammary environment for
      expression. Gene-disrupted mutants for SACOL0720 and SACOL0442 showed no growth
      defect in vitro but were attenuated during bovine IMI, causing infections with
      significant reductions in bacterial and somatic cell counts. The milk from the
      mammary quarters infected with these mutants also showed better appearance and
      composition than milk from quarters infected with the wild type. In conclusion,
      we have identified genes that are most likely important for S. aureus IMI. These
      represent novel candidates to include in a vaccine.

PMID- 23116585
TI  - AR-A014418 as a glycogen synthase kinase-3 inhibitor: anti-apoptotic and
      therapeutic potential in experimental spinal cord injury.
AB  - OBJECTIVES: We aimed to investigate the effects of AR-A014418, a strong inhibitor
      specific to GSK-3beta, on neuronal apoptosis and neuroprotection in the traumatic
      SCI model. MATERIALS AND METHODS: In this study, three groups were generated from
      36 Wistar rats; (1) control, (2) spinal cord trauma group created by clip
      compression technique after laminectomy, and (3) AR-A014418 (4mg/kg, i.p., DMSO)
      treatment group after laminectomy and spinal cord trauma. The TUNEL assay for
      apoptosis detection, immunohistochemical staining for bax and TGF-beta were
      applied in spinal cord tissues. For light microscopic examination, necrotic, and
      apoptotic cells were counted, and PMNL counting was applied to detect
      inflammation. Functional recovery was tested by field locomotor test in the 3rd
      and 7th days following surgery. RESULTS: In the trauma group, diffuse hemorrhage,
      cavitation, necrosis and edematous regions, degeneration in motor neurons and
      leukocyte infiltration were observed in gray matter. In the AR-A014418-treated
      groups, healthy cells were observed in more places compared to the trauma groups,
      however, cavitation, hemorrhagic, and edematous areas were seen in gray matter.
      In the AR-A014418-treatment groups, the number of apoptotic cells in the 3rd and
      7th days (respectively; p<0.05, p<0.01), were significantly decreased compared to
      the trauma groups, as were the levels of bax (p<0.01) and TGF-beta 1
      immunoreactivity. Results of the locomotor test were significantly increased in
      the treatment group (p<0.001) as compared to the trauma group. CONCLUSIONS: In
      this experimental spinal cord trauma model study neural apoptosis was
      significantly triggered in secondary damage developed after trauma, however,
      neurological healing was expedited by preventing mitochondrial apoptosis and
      reducing the inflammation by the potent inhibitor AR-A014418, which is GSK-3beta
      selective.

PMID- 23116587
TI  - Investigation of the persistence and transmission of MRSA CC 5 in pigs following
      intra-nasal inoculation.
AB  - MRSA CC5 spa type t002 appears to have a broad host range, has been isolated from
      animals and in-contact humans in Ireland and could potentially become established
      in pigs in Ireland. The aims of this study were to determine if MRSA CC5 spa type
      t002 could persist in the tissues of the porcine upper respiratory tract
      following intra-nasal inoculation; to determine the relative importance of
      environmental and animal sources of the bacterium in the transmission cycle and
      to determine the importance of the pharynx as a carriage site of Staphylococcus
      aureus and MRSA. Twelve pigs were inoculated intra-nasally with MRSA CC5 t002.
      After 1 or 6 days, the inoculated pigs were removed from the contaminated
      environment, were washed in an antiseptic solution and placed in a clean house
      with a group of naive pigs (in-contact group). Another group of naive pigs was
      placed in the contaminated environment to assess transmission from the
      environment (environmental group). Nasal swabs, environmental swabs and tissue
      samples from the upper respiratory tract were taken for MRSA culture. Infection
      rates were calculated for each group of exposed pigs. MRSA persisted in the
      pharyngeal tissues of 6 inoculated pigs for at least 30 days and higher counts of
      S. aureus were found in pharyngeal tissues than in other sites. In this study we
      were able to demonstrate the establishment of colonisation by MRSA CC5 spa type
      t002 in commercially sourced pigs already colonised by S. aureus; however,
      colonisation was sporadic despite the inoculation of large doses. Onward
      transmission via pig-to-pig contact or environmental contamination was possible
      and a significant difference was found between the proportion of pigs infected in
      the environmental group and the proportion infected in the in-contact group
      during the first 5 days. However, no significant difference was detected in
      overall infection rates between the 2 groups. The tissues of the pharynx were
      found to carry greater numbers of S. aureus than other tissues of the upper
      respiratory tract; therefore, pharyngeal carriage of MRSA and S. aureus in pigs
      may be more significant than previously thought.

PMID- 23116588
TI  - Characteristics and virulence factors of livestock associated ST9 methicillin
      resistant Staphylococcus aureus with a novel recombinant staphylocoagulase type.
AB  - Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA)
      sequence type 9 (ST9) is a potential source of zoonotic infection for humans. In
      this study, we investigated and compared the virulence profiles of MRSA ST9
      isolates from healthy swine and human clinical origins. A total of 152 MRSA ST9
      isolates, including 147 LA-MRSA isolates and 5 human clinical isolates, were
      studied for the accessory gene regulator (agr) and 20 enterotoxin genes (se),
      exfoliatoxin gene, and tst gene. The evolutionary history of staphylocoagulase
      (SC) in Taiwan MRSA ST9 was reconstructed based on phylogenetic and population
      genetics. The predominant type of LA-MRSA ST9 isolates (78.9%) was agr-II that
      differed from the predominant agr-I human clinical MRSA strains in Taiwan and the
      LA-MRSA ST398 lineage from Europe. Forty-nine percent of the LA-MRSA ST9 isolates
      carried a combination of enterotoxin gene cluster-2 (egc-2, seg, sei, sem, sen,
      seo, and seu) and tst. In addition, the Taiwan LA-MRSA ST9 and the human clinical
      ST9-MRSA contained a novel SC XIc subtype and had a unique history of evolution
      indicating a recent common ancestor. These findings suggest a cross-species
      transmission of this emerging ST9-SC XIc MRSA between swine and human.

PMID- 23116589
TI  - Root causes of intraoperative hypoglycemia: a case series.
AB  - STUDY OBJECTIVE: To describe the root causes of intraoperative hypoglycemic
      events. DESIGN: Retrospective analysis. SETTING: Large academic teaching
      hospital. MEASUREMENTS: Data from 80,379 ASA physical status 1, 2, 3, 4, and 5
      surgical patients were reviewed. Blood glucose values, insulin, oral hypoglycemic
      medication doses, and doses of glucose or other medications for hypoglycemia
      treatment were recorded. MAIN RESULTS: Hypoglycemia in many patients had multiple
      etiologies, with many cases (8 of 17) involving preventable errors. The most
      common root causes of hypoglycemia were ineffective communication, circulatory
      shock, failure to monitor, and excessive insulin administration. CONCLUSION:
      Intraoperative hypoglycemia was rare, but often preventable. Better communication
      among providers and between providers and patients may reduce the number of
      intraoperative hypoglycemic events. Many transient episodes of hypoglycemia did
      not result in any apparent complications, rendering their clinical importance
      uncertain. Critically ill patients in circulatory shock represent a group that
      may require close glucose monitoring.

PMID- 23116592
TI  - Genetic diversity and population structure of Sugarcane mosaic virus.
AB  - Sugarcane mosaic virus (SCMV) is one of the causal pathogens of mosaic diseases
      on sugarcane, maize, sorghum and some other graminaceous species with worldwide
      distribution. The global genetic diversity and molecular evolution of SCMV capsid
      protein (CP) gene were investigated with the nucleotide sequences available in
      the GenBank database. Phylogenetic analyses revealed that SCMV isolates clustered
      in relation to their original hosts, and geographically distinct isolates from
      maize or sugarcane clustered differently. The populations between maize and
      sugarcane showed frequent gene flows; but within maize or sugarcane geography
      distinct isolates had infrequent gene flow. Recombination existed in the region
      of CP cistron and 3'-untranslated region (UTR). Most of the codons in the CP gene
      were under negative selection or neutral evolution except for codons 27 and 48,
      which were under positive selection. This study provided systematic analyses of
      the evolutionary processes contributing to the observed diversification of SCMV
      populations.

PMID- 23116593
TI  - Discovery of a novel mastrevirus and alphasatellite-like circular DNA in
      dragonflies (Epiprocta) from Puerto Rico.
AB  - Geminiviruses have emerged as serious agricultural pathogens. Despite all the
      species that have been already catalogued, new molecular techniques continue to
      expand the diversity and geographical ranges of these single-stranded DNA viruses
      and their associated satellite molecules. Since all geminiviruses are insect
      transmitted, examination of insect vector populations through vector-enabled
      metagenomics (VEM) has been recently used to investigate the diversity of
      geminiviruses transmitted by a specific vector in a given region. Here we used a
      more comprehensive adaptation of the VEM approach by surveying small circular DNA
      viruses found within top insect predators, specifically dragonflies (Epiprocta).
      This 'predator-enabled' approach is not limited to viral groups transmitted by
      specific vectors since dragonflies can accumulate the wide range of viruses
      transmitted by their diverse insect prey. Analysis of six dragonflies collected
      from an agricultural field in Puerto Rico culminated in the discovery of the
      first mastrevirus (Dragonfly-associated mastrevirus; DfasMV) and alphasatellite
      molecule (Dragonfly-associated alphasatellite; Dfas-alphasatellite) from the
      Caribbean. Since DfasMV and Dfas-alphasatellite are divergent from the limited
      number of sequences that have been reported from the Americas, this study
      unequivocally demonstrates that there have been at least two independent past
      introductions of both mastreviruses and alphasatellites to the New World.
      Overall, the use of predacious insects as sampling tools can profoundly alter our
      views of natural plant virus diversity and biogeography by allowing the discovery
      of novel geminiviruses and associated satellite molecules without a priori
      knowledge of the types of viruses or insect vectors in a given area.

PMID- 23116590
TI  - Restless legs syndrome as a cause of sleep disturbances in cancer patients
      receiving chemotherapy.
AB  - CONTEXT: Sleep disturbances are frequent in cancer patients during chemotherapy;
      the contributory role of restless legs syndrome (RLS) in this setting has never
      been assessed. OBJECTIVES: This study investigated the role of RLS in causing
      sleep disturbances and altering the quality of life in cancer patients during
      chemotherapy. METHODS: Evaluation tools included the Pittsburgh Sleep Quality
      Index (PSQI), the RLS questionnaires, the Functional Assessment of Cancer Therapy
      General, and the Hospital Anxiety and Depression Scale for quality of life and
      anxiety/depression assessment. The study population was 173 cancer patients. The
      questionnaires were administered during the third chemotherapy cycle. Patients
      positive for RLS were reassessed six months after the end of chemotherapy.
      RESULTS: In all, 58.8% of patients reported experiencing sleep disturbances
      (PSQI>=5) and 20% screened positive for RLS. Neither sleep disturbances nor RLS
      was associated with anemia, neurotoxic cytotoxic drugs, or benzamide treatment. A
      direct relationship was found between the PSQI and RLS (P=0.007); both PSQI and
      RLS scores were significantly associated with poor quality of life (P=0.008 and
      0.01, respectively) and anxiety (P=0.0001 and 0.01, respectively). PSQI score
      also was associated with depression (P=0.0001). RLS persisted in four of the 25
      RLS-positive patients reassessed at six months after chemotherapy. RLS recovery
      was associated with a significant reduction in sleep disturbances and improvement
      in quality of life. CONCLUSION: RLS can be a contributory factor in sleep
      disturbances in cancer patients undergoing chemotherapy. Screening for RLS could
      aid in tailoring a potentially more efficacious treatment of such disturbances.

PMID- 23116594
TI  - An infectious full-length cDNA clone of duck Tembusu virus, a newly emerging
      flavivirus causing duck egg drop syndrome in China.
AB  - Duck Tembusu virus (TMUV) is a recently identified pathogenic flavivirus that
      causes severe egg drop and encephalitis in Chinese ducks and geese. It has been
      found to be most closely related to the mosquito-origin Tembusu virus and chicken
      Sitiawan virus reported in Malaysia. However, the ecological characteristics and
      the pathogenesis of duck TMUV are largely unknown. We report the construction of
      full-length cDNA clone of duck TMUV strain JXSP. The virus genome was reverse
      transcribed, amplified as seven overlapping fragments and successively ligated
      into the low copy number vector pWSK29 under the control of a T7 promoter.
      Transfection of BHK-21 cells with the transcribed RNA from the full-length cDNA
      clone resulted in production of highly infectious progeny virus. In vitro growth
      characteristics in BHK-21 cells and virulence in ducklings and BALB/c mice were
      similar for the rescued and parental viruses. This stable infectious cDNA clone
      will be a valuable tool for studying the genetic determinants of duck TMUV.

PMID- 23116596
TI  - Comparison of serum and urinary nephrin levels between normal pregnancies and
      severe preeclampsia.
AB  - OBJECTIVE: To compare the levels of urinary excretion of nephrin in women
      experiencing either normotensive or severe preeclamptic pregnancies, and to
      examine the relationship between urinary nephrin levels and clinical parameters
      of preeclampsia. STUDY DESIGN: In a case control study we collected serum and
      urine specimens from women with normal pregnancy (n=30) and from women with
      severe preeclampsia (n=43). Serum nephrin levels and urinary nephrin
      concentrations were measured in all patients. RESULTS: Both serum and urine
      concentrations of nephrin were significantly higher in the severe preeclamptic
      group than in the normal pregnancy group. In addition, we identified a
      significant relationship between urinary nephrin levels and urine protein
      concentrations in the severe preeclamptic group. Urine nephrin concentrations
      were also correlated with serum creatinine levels and with diastolic blood
      pressure in the severe preeclamptic group. CONCLUSION: The positive correlations
      observed in this study suggest that urinary nephrin excretion might play an
      important role in the pathogenesis of proteinuria during preeclampsia and could
      be a good indicator of renal damage.

PMID- 23116595
TI  - Possible contribution of fetal size and gestational age to myocardial tissue
      Doppler velocities in preterm fetuses.

PMID- 23116597
TI  - A randomized controlled trial of the effectiveness of brief-CBT for patients with
      symptoms of posttraumatic stress following a motor vehicle crash.
AB  - BACKGROUND: Motor vehicle crashes (MVCs) are leading contributors to the global
      burden of disease. Patients attending accident and emergency (A&E) after an MVC
      may develop symptoms of posttraumatic stress disorder (PTSD). There is evidence
      that brief cognitive behavioural therapy (B-CBT) can be effective in treating
      PTSD; however, there are few studies of the use of B-CBT to treat PTSD in MVC
      survivors. AIMS: This study examined the effects of B-CBT and a self-help program
      on the severity of psychological symptoms in MVC survivors at risk of developing
      PTSD. METHOD: Sixty participants who attended A&E after a MVC were screened for
      PTSD symptoms and randomized to a 4-weekly session B-CBT or a 4-week self-help
      program (SHP) booklet treatment conditions. Psychological assessments were
      completed at baseline (1-month post-MVC) and posttreatment (3- and 6-month follow
      ups) by utilizing Impact of Event Scale-Revised (IES-R) and Hospital Anxiety and
      Depression Scale (HADS). RESULTS: There were significant improvements in the
      measures of anxiety, depression, and PTSD symptoms over time. Participants
      treated with B-CBT showed greater reductions in anxiety at 3-month and 6-month
      follow-ups, and in depression at 6-month follow-up. A comparison of effect size
      favoured B-CBT for the reduction of anxiety and depression symptoms measured by
      HADS. A high level of pretreatment anxiety and depression were predictive of
      negative outcome at 6-month follow-up in the SHP condition. There was no
      differential effect on PTSD symptoms measured by IES-R. CONCLUSIONS: This trial
      supports the efficacy of providing B-CBT as a preventive strategy to improve
      psychological symptoms after an MVC.

PMID- 23116598
TI  - Phospholipase C gamma and ERK1/2 mitogen activated kinase pathways are
      differentially modulated by Trypanosoma cruzi during tissue invasion in human
      placenta.
AB  - Chagas' disease is caused by the haemophlagelated protozoan Trypanosoma cruzi (T.
      cruzi). During congenital transmission the parasite breaks down the placental
      barrier, however studies about the physiopathology of this process are scarce.
      Different signal transduction pathways are involved during cell invasion of the
      parasite. However, the possible role of those processes during tissue infection
      has not been studied. In the present study we analyzed the modulation of two
      signal transduction pathways, PLC-gamma and ERK1/2 MAPK, during ex vivo infection
      of human placental chorionic villi explants. Chorionic villi from healthy woman
      placentas were incubated in the presence or absence of 10(5) or 10(6)T. cruzi
      trypomastigotes (DM28c strain) with or without specific inhibitors for each
      pathway. Effective infection was tested determining parasite DNA by PCR. The
      activation of PLC-gamma and ERK1/2 MAPK signaling pathways was determined by
      western blotting and immunofluorescence. The low concentration of T. cruzi
      trypomastigotes activates both signaling pathways; however, the high
      concentration of parasite induces a modest activation of the PLC-gamma pathway
      and impairs the ERK1/2 MAPK pathway activation. Interestingly, inhibition of any
      of those signaling pathways did not prevent parasite infection, as it was
      previously shown in cell cultures. We conclude that both signal transduction
      pathways are modulated during ex vivo T. cruzi infection of human placental
      chorionic villi explants.

PMID- 23116599
TI  - DNA of Dientamoeba fragilis detected within surface-sterilized eggs of Enterobius
      vermicularis.
AB  - With no evidence of a cyst stage, the mode of transmission of Dientamoeba
      fragilis, an intestinal protozoon of common occurrence and suggested
      pathogenicity, is incompletely known. Numerous studies have suggested that eggs
      of intestinal nematodes, primarily Enterobius vermicularis (pinworm), can serve
      as vectors for D. fragilis, although attempts to culture D. fragilis from pinworm
      eggs have been unsuccessful and data from epidemiological studies on D.
      fragilis/pinworm co-infection have been conflicting. The aim of this study was to
      investigate whether we could detect D. fragilis DNA from pinworm eggs collected
      from routine diagnostic samples (cellophane tape) and surface-sterilised by
      hypochlorite. DNA was extracted from individual eggs and tested by PCR using D.
      fragilis- and E. vermicularis-specific primers; amplicons were sequenced for
      confirmation. In cellophane tape samples from 64 patients with unknown D.
      fragilis status we detected D. fragilis DNA in 12/238 (5%) eggs, and in a patient
      known to harbour D. fragilis we detected D. fragilis DNA in 39/99 (39%) eggs. The
      finding of D. fragilis DNA within eggs of E. vermicularis strongly supports the
      hypothesis of D. fragilis-transmission by pinworm and has implications for
      antimicrobial intervention as well as control and public health measures.

PMID- 23116601
TI  - Could circulating miRNAs contribute to cancer therapy?
AB  - The roles of circulating miRNAs in disease therapy remain largely unclear, but
      recent data suggests a role for these molecules in cancer. In patients with
      cancer, the levels of circulating miRNAs with tumor-suppressing capabilities
      increase and those with oncogenic activity decrease. In addition, the population
      of circulating miRNAs correlates highly with immune response, suggesting that
      circulating miRNAs could be driving anticancer effects through active immune
      defense and might be a novel strategy for cancer therapy.

PMID- 23116600
TI  - Optimized protocols for improving the likelihood of cloning recombinant progeny
      from Plasmodium yoelii genetic crosses.
AB  - Genetic cross is a powerful tool for studying malaria genes contributing to drug
      resistance, parasite development, and pathogenesis. Cloning and identification of
      recombinant progeny (RP) is laborious and expensive, especially when a large
      proportion of progeny derived from self-fertilization are present in the uncloned
      progeny of a genetic cross. Since the frequency of cross-fertilization affects
      the number of recombinant progeny in a genetic cross, it is important to optimize
      the procedure of a genetic cross to maximize the cross-fertilization. Here we
      investigated the factors that might influence the chances of obtaining RP from a
      genetic cross and showed that different Plasmodium yoelii
      strains/subspecies/clones had unique abilities in producing oocysts in a mosquito
      midgut. When a genetic cross is performed between two parents producing different
      numbers of functional gametocytes, the ratio of parental parasites must be
      adjusted to improve the chance of obtaining RP. An optimized parental ratio could
      be established based on oocyst counts from single infection of each parent before
      crossing experiments, which may reflect the efficiency of gametocyte production
      and/or fertilization. The timing of progeny cloning is also important; cloning of
      genetic cross progeny from mice directly infected with sporozoites (vs. frozen
      blood after needle passage) at a time when parasitemia is low (usually <1%) could
      improve the chance of obtaining RP. This study provides an optimized protocol for
      efficiently cloning RPs from a genetic cross of malaria parasites.

PMID- 23116602
TI  - Health-related quality of life in chronic myeloid leukemia.
AB  - The increased survival associated with treatments for CML emphasize the
      importance of understanding the HRQOL of newly diagnosed and previously treated
      CML patients with all phases of disease. Functional Assessment of Cancer Therapy
      Leukemia results from a phase 3 and a phase 2 trial are reported for over 900
      1st, 2nd, 3rd line CP, AP, and BP patients. Physical Well-being and Leukemia
      symptoms were worse for patients in later lines of therapy. Individuals with AP
      and BP CML had poorer HRQOL than individuals with CP CML. HRQOL of CML patients
      was predominantly consistent with the longitudinal clinical trajectory of the
      disease.

PMID- 23116603
TI  - Identification of indole-3-carboxylic acid as mediator of priming against
      Plectosphaerella cucumerina.
AB  - Plant resistance against the necrotrophic pathogen Plectosphaerella cucumerina is
      mediated by a combination of several hormonal-controlled signalling pathways. The
      priming agent beta-aminobutyric acid (BABA) is able to induce effective
      resistance against this pathogen by stimulating callose-rich cell wall
      depositions. In the present research it is demonstrated that BABA-Induced
      Resistance (BABA-IR) against P. cucumerina in Arabidopsis has additional
      components such as the induction of defences mediated by indolic derivatives.
      Chromatographic approach for the detection and characterization of metabolites
      enhanced by BABA compared with water-treated plants only when the challenge is
      present has been developed. The metabolites matching this criteria are considered
      to be primed by BABA. The analytic procedure is based on the combination of
      liquid chromatography (LC) with a triple quadrupole (TQD) detector in a precursor
      ion scanning mode. Using this analytical system a signal in negative electro
      spray mode of 160 m/z is primed by BABA in infected plants. A subsequent exact
      mass analysis in a quadrupole time-of-flight mass spectrometer demonstrated that
      this ion was the indole-derivative metabolite indole-3-carboxylic acid (I3CA).
      The identity of indole-3-carboxilic acid was definitively confirmed by comparing
      its retention time and fragmentation spectra with a commercial standard.
      Quantification of I3CA in primed plants showed that this indolic metabolite is
      specifically primed by BABA upon P. cucumerina infection, while other indolic
      compounds such as IAA and camalexin are not. Taking together these observations
      with the known role of callose in priming against this pathogen, suggests that
      priming is not a single mechanism but rather a multicomponent defence.

PMID- 23116604
TI  - Biodegradation of gasoline ether oxygenates.
AB  - Ether oxygenates such as methyl tertiary butyl ether (MTBE) are added to gasoline
      to improve fuel combustion and decrease exhaust emissions. Ether oxygenates and
      their tertiary alcohol metabolites are now an important group of groundwater
      pollutants. This review highlights recent advances in our understanding of the
      microorganisms, enzymes and pathways involved in both the aerobic and anaerobic
      biodegradation of these compounds. This review also aims to illustrate how these
      microbiological and biochemical studies have guided, and have helped refine,
      molecular and stable isotope-based analytical approaches that are increasingly
      being used to detect and quantify biodegradation of these compounds in
      contaminated environments.

PMID- 23116606
TI  - What is the value of hospital mortality indicators, and are there ways to do
      better?
AB  - Monitoring hospital performance using patient safety indicators is one of the key
      components of healthcare reform in Australia. Mortality indicators, including the
      hospital standardised mortality ratio and deaths in low mortality diagnosis
      reference groups have been included in the core national hospital-based outcome
      indicator set recommended for local generation and review and public reporting.
      Although the face validity of mortality indicators such as these is high, an
      increasing number of studies have demonstrated that there are concerns regarding
      their internal, construct and criterion validity. Use of indicators with poor
      validity has the consequence of potentially incorrectly classifying hospitals as
      performance outliers and expenditure of limited hospital staff time on activities
      which may provide no gain to hospital quality and safety and may in fact cause
      damage to morale. This paper reviews the limitations of current approaches to
      monitoring hospital quality and safety performance using mortality indicators. It
      is argued that there are better approaches to improving performance than
      monitoring with mortality indicators generated from hospital administrative data.
      These approaches include use of epidemiologically sound, clinically relevant data
      from clinical-quality registries, better systems of audit, evidence-based
      bundles, checklists, simulators and application of the science of complex
      systems.

PMID- 23116607
TI  - Diagnostic accuracy of buffy coat culture compared to total blood culture in late
      onset sepsis of the newborn.
AB  - OBJECTIVES: To study the potential of buffy coat culture as a diagnostic tool for
      neonatal late-onset sepsis. METHODS: This was a study of diagnostic accuracy in
      newborn infants born at 28-41 weeks of gestation, weighing >800g, with >=8 points
      on the NOSEP-1 scale. Paired samples for total blood culture (TBC) and buffy coat
      culture were drawn. We established the positivity rate, sensitivity, specificity,
      predictive values, and likelihood ratios, and compared time to positivity and
      contamination rates. RESULTS: Fifty-two newborns were included in the study.
      Twenty-one TBC and 22 buffy coat cultures were positive. The positivity rate for
      TBC was 40.4% and for buffy coat culture was 42.3% (p=not significant). Three TBC
      were positive with negative buffy coat culture. Four buffy coat cultures were
      positive with negative TBC; Kappa agreement was 0.723, p <0.001. Buffy coat
      culture sensitivity was 86% (95% confidence interval (CI) 68.5-95.4%),
      specificity 87% (75.4-93.7%), positive predictive value 82% (65.4-91.1%),
      negative predictive value 90% (77.9-96.8%), positive likelihood ratio 6.64 (2.79
      15.05), and negative likelihood ratio 0.16 (0.05-0.42). We found no difference in
      time to positivity in hours; Wilcoxon Z=1224, p=0.22. The contamination rate was
      1.9% for both methods. CONCLUSIONS: Buffy coat culture is as good as TBC for the
      microbiological diagnosis of late-onset sepsis of the newborn. Buffy coat culture
      allows the use of remaining plasma for further analysis.

PMID- 23116605
TI  - Obesity increases cerebrocortical reactive oxygen species and impairs brain
      function.
AB  - Nearly two-thirds of the population in the United States is overweight or obese,
      and this unprecedented level of obesity will undoubtedly have a profound impact
      on overall health, although little is currently known about the effects of
      obesity on the brain. The objective of this study was to investigate cerebral
      oxidative stress and cognitive decline in the context of diet-induced obesity
      (DIO). We demonstrate for the first time that DIO induces higher levels of
      reactive oxygen species (ROS) in the brain and promotes cognitive impairment.
      Importantly, we also demonstrate for the first time in these studies that both
      body weight and adiposity are tightly correlated with the level of ROS.
      Interestingly, ROS were not correlated with cognitive decline in this model.
      Alterations in the antioxidant/detoxification Nrf2 pathway, superoxide dismutase,
      and catalase activity levels were not significantly altered in response to DIO.
      However, a significant impairment in glutathione peroxidase was observed in
      response to DIO. Taken together, these data demonstrate for the first time that
      DIO increases the levels of total and individual ROS in the brain and highlight a
      direct relationship between the amount of adiposity and the level of oxidative
      stress within the brain. These data have important implications for understanding
      the negative effects of obesity on the brain and are vital to understanding the
      role of oxidative stress in mediating the effects of obesity on the brain.

PMID- 23116608
TI  - Epidemiology of urban dog-related injuries requiring rabies post-exposure
      prophylaxis in Marseille, France.
AB  - BACKGROUND: Dog bites are a serious public health concern. Besides injuries and
      the adverse psychological impacts, dog bites can be complicated by infections
      including rabies, which has the highest case-fatality rate of all infectious
      diseases. METHODS: Dog-associated injuries occurring in the city of Marseille,
      France were investigated in 245 individuals among patients presenting to the
      rabies treatment center over a 4-year period. RESULTS: Male patients were more
      likely to report dog bites compared to female patients (66.5% vs. 33.5%; odds
      ratio 2.25, 95% confidence interval 1.72-2.93). The mean age of injured patients
      was 32 years (range 1-85 years). Children and young adults under 30 years of age
      were more than four times more likely to report dog bites compared to others.
      Most cases occurred outdoors (73.0%) - in public areas (38.0%) - and involved
      animals of unknown owners in 56.3% of the cases. Only 28.2% of dogs were
      available for observation. Most patients (63.7%) received complete rabies post
      exposure prophylaxis. The distribution of dog bites in the city was not
      homogeneous and the incidence of bites was significantly higher in some areas.
      Eleven percent of patients declared having been bitten by dogs whose owner was a
      street beggar, and a clustered distribution was evidenced for these cases in one
      area of the city. CONCLUSIONS: Programs offering low-cost rabies vaccination and
      veterinary care to pets belonging to the group of street beggars should be
      considered. Such programs may be implemented in other large cities in France and
      Europe where street beggars are frequently seen.

PMID- 23116609
TI  - A study of adherence to antibiotic treatment in ambulatory respiratory
      infections.
AB  - OBJECTIVES: To assess the different types of antibiotic-taking behavior and to
      compare self-reported with objectively measured adherence to antibiotic regimens
      in respiratory infections. METHODS: This was a prospective study of patients with
      suspected bacterial pharyngitis and lower respiratory tract infections recruited
      from five primary care clinics in Catalonia. Adherence to various antibiotic
      regimens was assessed by the Medication Event Monitoring System (MEMS), which
      recorded every opening of the patient's bottle of tablets, and a self-reported
      adherence question. The outcome variables were antibiotic-taking adherence,
      correct dosing, and timing adherence. RESULTS: A total of 428 patients were
      included in the analysis. Five types of antibiotic use behavior were observed:
      excellent adherence (130 patients, 30.4%), acceptable adherence over time (53;
      12.4%), declining adherence over time (123; 28.7%), non-adherence to correct
      dosing (108; 25.2%), and unacceptable adherence (14; 3.3%). Excellent adherence
      was significantly associated with the number of daily doses of antibiotic and
      antibiotic duration. A total of 254 patients reported never forgetting to take
      the antibiotic (59.3%), achieving a negative predictive value of 100% and a
      positive predictive value of 51.2%. CONCLUSIONS: Outpatients with respiratory
      infections treated with antibiotics showed poor adherence outcomes. Self-reported
      adherence was remarkably higher than that observed with the use of MEMS and
      failed to predict true patient adherence.

PMID- 23116610
TI  - Malaria in Laconia, Greece, then and now: a 2500-year-old pattern.
AB  - BACKGROUND: Malaria is still an active threat in many areas of the world. In
      Greece, in an area of the Laconia region, malaria epidemics have been recorded
      since as early as the 5(th) century BC. A local outbreak of malaria was reported
      in the summer/autumn of 2011. METHOD: A comparative research study of historical
      and modern sources was carried out in order to explore the malaria outbreaks
      occurring in the area of Laconia, Greece. RESULTS: The study revealed that the
      central area (Elos and Skala), the peak season (early autumn), the Plasmodium
      species (P. vivax), the mosquito vector (Anopheles sacharovi), and the risk
      factors (wetlands and population movements) have, more or less, remained
      unchanged throughout the 2500-year span in Laconia. CONCLUSIONS: Unique regional
      features preserve a seemingly recurring pattern of malaria outbreaks in this area
      of Greece. This study, based on low-cost effective research, offers a clear
      public health message. The Greek authorities responsible for health policy could
      build upon these findings in order to achieve the desired eradication.

PMID- 23116611
TI  - Therapeutic hypothermia in term infants after perinatal encephalopathy: the last
      5 years in Switzerland.
AB  - BACKGROUND: Therapeutic hypothermia (TH) following perinatal asphyxial
      encephalopathy in term infants improves mortality and neurodevelopmental outcome.
      In Europe, most neonatal units perform active cooling whereas in Switzerland
      passive cooling is predominantly used. AIMS: (i) To determine how many infants
      were cooled within the last 5years in Switzerland, (ii) to assess the cooling
      methods, (iii) to evaluate the variation of temperature of different cooling
      methods, and (iv) to evaluate the use of neuromonitoring. STUDY DESIGN:
      Retrospective cohort study. PATIENTS: Notes of all cooled term infants between
      March 2005 and December 2010 in 9 perinatal and two paediatric intensive care
      centres were retrospectively reviewed. Active cooling was compared to passive
      cooling alone and to passive cooling in combination with gel packs. RESULTS: 150
      infants were cooled. Twenty-seven (18.2%) were cooled actively, 34 (23%)
      passively and 87 (58.8%) passively in combination with gel packs. Variation of
      temperature was significantly different between the three methods. Passive
      cooling had a significant higher variation of temperature (SD of 0.89) than both
      passive cooling in combination with gel packs (SD of 0.79) and active cooling (SD
      of 0.76). aEEG before TH was obtained in 35.8% of the infants and 86.5% had full
      EEG. One cUS was performed in 95.3% and MRI in 62.2% of the infants. CONCLUSION:
      Target temperature can be achieved with all three cooling methods. Passive
      cooling has the highest variation of temperature. Neuromonitoring should be
      improved in Swiss neonatal and paediatric intensive care units. Our results
      stress the importance of national registries.

PMID- 23116612
TI  - Presentation and prognosis of cardiac involvement in hepatitis C virus-related
      vasculitis.
AB  - Cardiac manifestation in primary systemic vasculitides is associated with poor
      outcomes, leading to the use of immunosuppressive therapy. In contrast, the
      spectrum and the outcome of cardiac involvement in the setting of mixed
      cryoglobulinemia vasculitis (CryoVas) have never been evaluated. To describe the
      clinical presentation and to evaluate clinical outcomes of cardiac manifestations
      during hepatitis C virus (HCV)-related mixed CryoVas, the clinical records of 165
      consecutive patients with HCV-related mixed CryoVas followed from January 1,
      1993, to January 1, 2010, were reviewed. Of the 165 patients with HCV-related
      mixed CryoVas, 7 (4%) had cardiac manifestations. Thoracic pain and congestive
      heart failure manifestations were the main clinical manifestations (n = 4 [57%]
      each). Cardiac imaging showed dilated cardiomyopathy in 5 patients and
      hypertrophic cardiomyopathy in 1. In multivariate analysis, patients with cardiac
      manifestations had more frequent B-cell lymphoma (odds ratio 18.1, 95% confidence
      interval 2.8 to 116.7, p = 0.0023) and gastrointestinal involvement (odds ratio
      14.6, 95% confidence interval 2.0 to 104.9, p = 0.0078). All cardiac
      manifestations were reversible early after the initiation of corticosteroids and
      aggressive immunosuppressive therapy. However, after a median follow-up period of
      19 months, 3 patients (43%) had died. Respective 6-month, 1-year, and 2-year
      survival rates in patients with and without cardiac involvement were 86% and 99%,
      71% and 96%, and 48% and 90% (hazard ratio 5.01, p = 0.003). In conclusion,
      cardiac damage is a rare manifestation of HCV-related mixed cryoglobulinemia
      vasculitis. Cardiac involvement is associated with B-cell lymphoma and life
      threatening manifestations. Despite favorable early outcomes, patients with
      cardiac damage had poorer survival than those without.

PMID- 23116613
TI  - The human glucagon-like peptide-1 analogue liraglutide regulates pancreatic beta
      cell proliferation and apoptosis via an AMPK/mTOR/P70S6K signaling pathway.
AB  - Glucagon-like peptide-1 (GLP-1), an effective therapeutic agent for the treatment
      of diabetes, has been proven to protect pancreatic beta cells through many
      pathways. Recent evidence demonstrates that AMP-activated protein kinase (AMPK),
      as a metabolic regulator, coordinates beta-cell protein synthesis through
      regulation of the mammalian target of rapamycin (mTOR) signaling pathway. The
      purpose of the present study was to explore whether liraglutide, a human GLP-1
      analogue, protects beta cells via AMPK/mTOR signaling. We evaluated INS-1 beta
      cell line proliferation using the Cell Counting Kit-8, and examined the effect of
      GLP-1 on cellular ATP levels using an ATP assay kit. mTOR pathway protein
      expression levels were tested by Western blotting and glucolipotoxicity-induced
      cell apoptosis was evaluated by flow cytometry. Liraglutide increased beta-cell
      viability at an optimum concentration of 100 nmol/L in the presence of 11.1 or 30
      mmol/L glucose. Liraglutide (100 nmol/L) activated mTOR and its downstream
      effectors, 70-kDa ribosomal protein S6 kinase and eIF4E-binding protein-1, in INS
      1 cells. This effect was abated by pathway blockers: the AMPK activator AICAR and
      the mTOR inhibitor rapamycin. Furthermore, the effect of liraglutide on beta-cell
      proliferation was inhibited by AICAR and rapamycin. Liraglutide increased
      cellular ATP levels. In addition, liraglutide protected beta cells from
      glucolipotoxicity-induced apoptosis. This response was also prevented by
      rapamycin treatment. These results suggest that the enhancement of beta-cell
      proliferation by that GLP-1 receptor agonist liraglutide is mediated, at least in
      part, by AMPK/mTOR signaling. Liraglutide also prevents beta-cell
      glucolipotoxicity by activating mTOR.

PMID- 23116615
TI  - Influence of dyeing auxiliaries on AB74 dye degradation by UV/H2O2 process.
AB  - The effect of dyeing auxiliaries on UV/H(2)O(2) removal of an indigoid dye, Acid
      Blue 74 (AB74) from the solution was investigated. The inhibition effect of
      anions including carbonate, bicarbonate and chloride on the process efficiency
      was evaluated in terms of color removal and total organic carbon (TOC) abatement.
      The presence of carbonate, bicarbonate and chloride anions had no considerable
      effect on the total decolorization time. However, the degradation efficiency of
      the process was enhanced by bicarbonate anion during the first 80 min of the
      process. During this period, the formation of active oxygen species such as
      CO(3)(-),HCO(4)(-)a nd O(2)(-) that participate in the degradation process of
      AB74 increases the degradation rate, in spite of the consumption of hydroxyl
      radicals by these anions. After this period, the overall efficiency was
      considerably decreased. Adding the chloride had less decreasing effect compared
      to the bicarbonate. The order of anions as AB74 degradation inhibitor in this
      study could be concluded as: [Formula: see text] .

PMID- 23116614
TI  - Effects of electroacupuncture Zusanli (ST36) on food intake and expression of
      POMC and TRPV1 through afferents-medulla pathway in obese prone rats.
AB  - OBJECTIVE: The purpose of this study was to determine the effects of
      electroacupuncture (EA) ST36 on food intake and body weight in obese prone (OP)
      rats compared to obese resistant (OR) strain on a high fat diet. The influences
      of EA on mRNA levels of pro-opiomelanocortin (POMC), transient receptor potential
      vanilloid type-1 (TRPV1), and neuronal nitric oxide synthase (nNOS) were also
      examined in the medulla regions and ST36 skin tissue. METHODS: Advanced EA ST36
      was conducted in two sessions of 20 min separated by an 80 min interval for 7
      days. Food intake and body weight were recorded in conscious rats every day. Real
      time PCR was conducted in the micropunches of the medulla regions and skin
      tissues at the end of the treatment. RESULTS: Food intake and body weight were
      significantly reduced by advanced EA ST36 in OP rats, but slightly decreased in
      OR strain and sham-EA rats. Advanced EA ST36 produced a marked increase in POMC
      mRNA level in the nucleus tractus solitarius (NTS) and hypoglossal nucleus (HN)
      regions. TRPV1 and nNOS mRNAs were simultaneously increased in the NTS/gracile
      nucleus regions and in the ST36 skin regions by the EA treatment in OP rats.
      CONCLUSIONS: We conclude that advanced EA ST36 produces an up-regulation of
      anorexigenic factor POMC production in the NTS/HN, which inhibits food intake and
      reduces body weight. EA-induced expression of TRPV1-nNOS in the ST36 and the
      NTS/gracile nucleus is involved in the signal transduction of EA stimuli via
      somatosensory afferents-medulla pathways.

PMID- 23116616
TI  - A novel plant based model for developing microsurgical anastomotic skills.

PMID- 23116617
TI  - School food, politics and child health.
AB  - OBJECTIVE: An analysis undertaken jointly in 2009 by the UN World Food Programme,
      The Partnership for Child Development and the World Bank was published as
      Rethinking School Feeding to provide guidance on how to develop and implement
      effective school feeding programmes as a productive safety net and as part of the
      efforts to achieve Education for All. The present paper reflects on how
      understanding of school feeding has changed since that analysis. DESIGN: Data on
      school feeding programme outcomes were collected through a literature review.
      Regression models were used to analyse relationships between school feeding costs
      (from data that were collected), the per capita costs of primary education and
      Gross Domestic Product per capita. Data on the transition to national ownership,
      supply chains and country examples were collected through country case studies.
      RESULTS: School feeding programmes increase school attendance, cognition and
      educational achievement, as well as provide a transfer of resources to households
      with possible benefits to local agricultural production and local market
      development. Low-income countries exhibit large variations in school feeding
      costs, with concomitant opportunities for cost containment. Countries are
      increasingly looking to transition from externally supported projects to national
      programmes. CONCLUSIONS: School feeding is now clearly evident as a major social
      programme in most countries with a global turnover in excess of $US 100 billion.
      This argues for a continuing focus on the evidence base with a view to helping
      countries ensure that their programmes are as cost-effective as possible. Clear
      policy advice has never been more important.

PMID- 23116618
TI  - Glucose-dependent regulation of AMP-activated protein kinase in MIN6 beta cells
      is not affected by the protein kinase A pathway.
AB  - AMP-activated protein kinase (AMPK) is a sensor of cellular energy status. In
      pancreatic beta cells, glucose induces the dephosphorylation of Thr172 within the
      catalytic subunit and the inactivation of the AMPK complex. Here we demonstrate
      that glucose also activates protein kinase A (PKA), leading to the
      phosphorylation of AMPKalpha at Ser485 and Ser497. However, these modifications
      do not impair the phosphorylation of Thr172 by upstream kinases, and
      phosphorylation of Thr172 does not affect the phosphorylation of AMPKalpha by PKA
      either. Thus, although phosphorylation of Thr172 and Ser485/Ser497 are inversely
      correlated in response to glucose, they follow an independent regulation.

PMID- 23116619
TI  - Does reflective web-based discussion strengthen nursing students' learning
      experiences during clinical training?
AB  - The aim of this research was to study how a web-based discussion forum can be
      used as a supervision tool during nursing students' clinical training. The study
      emphasises peer support and its importance for the students. The empirical
      research was carried out at a Finnish university of applied sciences. 25 nursing
      students took part in web-based discussion during their eight-week clinical
      training period. All in all, 395 comments were submitted. The material was
      analysed by using categorisation and a thematic analysis process. Finally, the
      results were reported using a modified Salmon's (2002) 5-stage model of Teaching
      and Learning On-line and Mezirow's (1981) levels of reflection. The students
      motivated each other by sharing their feelings and experiences. They noticed the
      value of peer support and started to learn from each other as well. By reflecting
      on their experiences, the students progressed in their learning process and at
      the same time advanced their reflective thinking process. This combination of
      theoretical knowledge and practice, based on the students' needs and interests,
      could lead to a deeper understanding which could also result in better clinical
      skills. This method offers the lecturers the possibility to support and follow
      the professional growth process in a new evidence-based manner. 

PMID- 23116620
TI  - Genotoxic and morphological damage in Hippocampus reidi exposed to crude oil.
AB  - The present article investigates the responses of Hippocampus reidi exposed to
      crude oil (10mL/L) for time periods that are characteristic of acute (12, 24, 48
      and 96h) and subchronic (168 and 336h) and its recovery at 168h, such as to
      assess H. reidi as a good sentinel species. These responses were examined by
      genotoxic and morphologic analyses. There was a control group (n=8) for each
      group exposed to crude oil (n=8). The results revealed the occurrence of
      genotoxic damage in erythrocytes of all specimens exposed to crude oil. The
      damage index (DI) observed for all exposure times were significantly higher
      compared to those of the respective control groups; the highest DI was observed
      in specimens exposed to crude oil for 168h. The group exposed to crude oil for
      96h had the highest values of micronuclei than all other exposure times.
      Microscopic inspection of the H. reidi gills revealed the presence of several
      histopathological changes, all of which were minor severity (structural normal
      gills). The recovery experiment revealed a significant reduction in genotoxic
      damages, however the period of 168h was not sufficient to recuperate the
      histopathology damages. The Seahorse has presented significant genotoxic
      responses after exposure to crude oil. Furthermore, it is a sedentary fish and is
      widely distributed; in conclusion this specie can be considered an excellent
      sentinel organism.

PMID- 23116621
TI  - Evaluation of in vitro and in vivo toxic effects of newly synthesized
      benzimidazole-based organophosphorus compounds.
AB  - This paper reports the toxic properties of eight newly synthesized benzimidazole
      based organophosphorus (OP) compounds in Xenopus laevis in both in vivo and in
      vitro conditions. For both experiments, a commercial solution of azinphos methyl
      (AzM, Gusathion M WP25) was used as a reference compound. The 24-h median lethal
      concentrations (LC50) of all tested compounds were determined for 46th stage
      tadpoles in the range of 9.54-140.0 MUM. For evaluation of the lethality of the
      compounds, the activity of the enzyme biomarkers acetylcholinesterase (AChE),
      carboxylesterase, glutathione S-transferase (GST), glutathione peroxidase,
      glutathione reductase, lactate dehydrogenase, aspartate aminotransferase, and
      alanine aminotransferase were determined in vivo in X. laevis tadpoles exposed to
      three concentrations (LC50, LC50/2, and LC50/4) of tested compounds. All exposure
      concentrations of AzM and seven of eight tested compounds caused CaE inhibition
      in in vivo conditions. Furthermore, the AChE inhibition capacity of tested
      compounds in commercial electric eel AChE and in X. laevis homogenates and also
      CaE inhibition capacity in only X. laevis homogenates were assayed for a 30-min
      in vitro exposure period. Eight OP compounds did not inhibit AChE activity more
      than 23 percent, but AzM exposure inhibited AChE activity by 26 percent for X.
      laevis homogenates and 97 percent for electric fish AChE in in vitro conditions.
      Also, CaE inhibition levels in X. laevis tadpole homogenates were 46 percent for
      AzM and between 8 percent and 33 percent for other compounds in in vitro
      conditions.

PMID- 23116622
TI  - Heavy metals assessment in urban soil around industrial clusters in Ghaziabad,
      India: probabilistic health risk approach.
AB  - Metal contamination in the urban soil in the industrial city of Ghaziabad
      district was investigated. Spatial distribution of Cu, Cr, Pb, Cd, Zn, Mn, Fe and
      Ni in the urban soil was produced. The mean Cu, Cr, Pb, Cd, Zn, Mn, Fe and Ni
      contents in the urban topsoil samples (122, 288, 147, 0.4, 187, 386, 21,433 and
      147mg/kg, respectively) were compared with the mean concentrations for other
      cities around the world. Cu, Cr, Pb, Zn and Ni concentrations appears to be
      higher than many other cities in the world. Non-cancer risk (Hazard Index) and
      cancer risk of children and adults due to exposure to the urban soil were
      estimated using 95th percentile values of total metal concentrations. Cluster
      analysis classified the sampling sites into three groups. Group 1 sites near
      commercial, industrial or dumpsite showed relatively higher concentrations of
      metals as compared to group 2 and 3 that were basically commercial or residential
      sites. It clearly indicates significant effects of rapid urbanization and
      industrialization in the last few decades in Ghaziabad. Correlation analysis and
      principal component analysis indicated common industrial source for Cu, Pb and Zn
      for group 1 sites. Cr may have point anthropogenic source. Except for Zn and Ni
      in group 2 sites, other metals may have come from natural sources while in group
      3, all metals may have lithogenic source. Combined (ingestion, dermal and
      inhalation) hazard index (HI) values for children exceeded the safe level (HI=1)
      for Cr (2.21) and Pb (0.67) close to 1. Cancer risk due to Cr, Pb, Cd and Ni were
      within acceptable range (1E-06 to 1E-04).

PMID- 23116624
TI  - Cellular responses and bioremoval of nonylphenol and octylphenol in the
      freshwater green microalga Scenedesmus obliquus.
AB  - The removal of nonylphenol (NP) and octylphenol (OP) by the freshwater green
      microalga Scenedesmus obliquus was studied in cultures exposed to different
      concentrations of NP and OP for 5 days. In most cases, low NP and OP
      concentrations (<1 mg/L) did not affect the growth, fluorescence transient
      (F(v)/F(m)), photosynthetic pigments and cell ultrastructure of S. obliquus,
      whereas high NP and OP concentrations (>1 mg/L) suppressed algal growth,
      decreased F(v)/F(m) and photosynthetic pigments, and destroyed algal
      ultrastructure. S. obliquus had a rapid and high ability to remove NP and OP.
      After 5 days of culturing, >89 percent NP and >58 percent OP were removed by this
      alga, with the highest removal efficiency being near 100 percent. The removal of
      NP and OP was mainly caused by algal degradation. Extracellular NP contents of S.
      obliquus were lower than intracellular NP contents, with the ratios changing from
      0 to 0.74. However, most of extracellular OP contents of S. obliquus were higher
      than intracellular OP contents, with the ratios changing from 0.74 to 2.15. The
      two alkylphenols exhibited a high bioconcentration potential, with one-day
      bioconcentration factors (BCF) of NP and OP varying between 3393 to 13262 and 949
      to 3227, respectively. After 5 days of culturing, high BCF values were still
      recorded when NP and OP initial concentrations were higher than 0.5 mg/L. These
      results demonstrated potential application of this algal species in the removal
      of organic contaminants including alkylphenols in addition to nutrients and
      metals.

PMID- 23116623
TI  - In situ biomonitoring of the genotoxic effects of vehicular pollution in
      Uberlandia, Brazil, using a Tradescantia micronucleus assay.
AB  - The growing number of cars in large cities is directly linked to changes in the
      chemical composition of urban air, which has increasingly high concentrations of
      potentially genotoxic chemicals. Therefore, discovering and monitoring the risks
      associated with exposure to atmospheric pollutants is indispensible for
      preventing environmental and health problems. Because of the lack of reliable
      data regarding the air quality in the city of Uberlandia, the present study
      sought to test whether the genotoxic risks in areas with different levels of
      vehicular traffic can be measured using the Tradescantia micronucleus assay (Trad
      MN). Therefore, more than twenty inflorescences were exposed to locations with
      different amounts of vehicular traffic twice per year from the winter of 2006 to
      the summer of 2011. The inflorescences were then analysed to determine the
      micronucleus (MN) frequency. In addition, we sought to determine the influence of
      factors linked to city climate on the MN frequencies obtained at each monitored
      location. Our results show that, although low relative humidity positively
      influenced MN formation in Tradescantia pallida tetrads, the major determining
      factor for clastogenic events was the level of vehicular traffic at the locations
      monitored over the five-year study.

PMID- 23116625
TI  - Optimizing taxane use in MBC in the emerging era of targeted chemotherapy.
AB  - The first-generation taxanes, conventional paclitaxel and docetaxel, are
      established treatment options for adjuvant and metastatic breast cancer (MBC).
      However, these agents have limitations, including primary/secondary resistance
      and harsh toxicities. The introduction of paclitaxel albumin represents a
      significant advance in taxane therapy as the first of a new generation of
      taxanes. This agent utilizes albumin pathways to achieve enhanced and targeted
      drug delivery to the tumour. The lack of solvent also means that it is well
      tolerated, despite the lack of premedications. Paclitaxel albumin is licensed in
      the United States and Europe as >=2nd-line therapy in MBC (260mg/m(2) once every
      three weeks), but emerging evidence suggests it has activity in various settings
      as weekly therapy and in combination with other agents. Additional strategies to
      optimize taxane-based therapy are also being evaluated, including the possibility
      of tailoring treatment according to patient/disease characteristics, identifying
      predictive biomarkers and evaluating other novel taxanes.

PMID- 23116626
TI  - Extended adjuvant endocrine therapy in hormone dependent breast cancer: the
      paradigm of the NCIC-CTG MA.17/BIG 1-97 trial.
AB  - Early hormone-receptor-positive breast cancer is a chronic relapsing disease that
      can remain clinically silent for many years. The NCIC-CTG MA.17/BIG 1-97 trial
      randomized disease-free early breast cancer patients who had received five years
      of adjuvant tamoxifen to either letrozole or placebo and was the first to
      demonstrate a benefit with extended endocrine therapy. MA.17/BIG 1-97 was stopped
      at the first interim analysis because disease free survival was strongly
      prolonged in the letrozole arm. Subsequent subset analyses and longer follow up
      have shown that this therapy improved survival across all groups, particularly
      among women with node-positive disease and those that were pre-menopausal at time
      of study enrolment. The MA.17/BIG 1-97 study should be considered a paradigm for
      extended adjuvant endocrine therapy in hormone-receptor-positive early breast
      cancer.

PMID- 23116627
TI  - Pili of gram-positive bacteria: roles in host colonization.
AB  - In the last decade, pili, which are encoded within pathogenicity islands, have
      been found in many Gram-positive bacteria, including the major streptococcal and
      enterococcal pathogens. These long proteinaceous polymers extending from the
      bacterial surface are constituted of covalently linked pilin subunits, which play
      major roles in adhesion and host colonization. They are also involved in biofilm
      formation, a characteristic life-style of the bacteria constituting the oral
      flora. Pili are highly immunogenic structures that are under the selective
      pressure of host immune responses. Indeed, pilus expression was found to be
      heterogeneous in several bacteria with the co-existence of two subpopulations
      expressing various levels of pili. The molecular mechanisms underlying this
      complex regulation are poorly characterized except for Streptococcus pneumoniae.
      In this review, we will discuss the roles of Gram-positive bacteria pili in
      adhesion to host extracellular matrix proteins, tissue tropism, biofilm
      formation, modulation of innate immune responses and their contribution to
      virulence, and in a second part the regulation of their expression. This overview
      should help to understand the rise of pili as an intensive field of investigation
      and pinpoints the areas that need further study.

PMID- 23116628
TI  - Intracellular trehalase activity is required for development, germination and
      heat-stress resistance of Aspergillus niger conidia.
AB  - The disaccharide trehalose is known as a stress protectant in several kinds of
      organisms, including fungi, where it is a major carbohydrate in resting
      structures, e.g. asexual conidia. The gene encoding the enzyme responsible for
      degradation of intracellular trehalose, treB, was deleted and the phenotype was
      analyzed in terms of morphology, trehalose content during conidial outgrowth and
      stress tolerance. The mutant conidiophores produced fewer and less viable spores,
      and during early stages of germination the internal levels of trehalose were
      higher compared to the wild type. When subjecting the mutant to various stresses
      (weak acid and salt), no increased sensitivity could be observed, but in line
      with previous observations, e.g. in Aspergillus nidulans, Aspergillus niger
      DeltatreB spores in a very early stage of germination were less sensitive to heat
      stress. In contrast, when subjecting resting spores to 55  degrees C, an intact
      treB gene was essential for survival. This finding suggests that trehalose
      mobilization is required to facilitate cell recovery after heat-induced damage.

PMID- 23116629
TI  - International medical graduates mandated to practise in rural Australia are
      highly unsatisfied: results from a national survey of doctors.
AB  - OBJECTIVES: Rural communities worldwide are increasingly reliant on international
      medical graduates (IMGs) to provide health care access, with many countries
      utilising health policies which mandate IMGs to practise only in rural designated
      areas of (medical) workforce shortage for many years. The objective of this study
      is to analyse the satisfaction of IMGs in their current work location,
      particularly in relation to the effect of mandating IMGs to small rural
      communities. METHODS: We used data of 3502 general practitioners (GPs) from Wave
      2 of the Medicine in Australia: Balancing Employment and Life (MABEL)
      longitudinal study of Australian doctors. The main outcome measures were the
      level of professional and non-professional satisfaction expressed by GPs with
      respect to various job and social aspects. RESULTS: We found that non
      professional satisfaction of mandated IMGs was significantly lower across all
      social aspects, whilst professional satisfaction was also significantly lower for
      most job aspects relating to their professional autonomy. In contrast, non
      mandated IMGs were similarly satisfied compared to Australian trained GPs.
      CONCLUSIONS: Mandated IMGs are currently filling a critical shortage in rural
      areas of Australia. However, long-term success of this policy is problematic
      unless outstanding issues affecting their significantly reduced professional and
      non-professional satisfaction can be addressed.

PMID- 23116630
TI  - Use of national clinical databases for informing and for evaluating health care
      policies.
AB  - Policy-makers and analysts could make use of national clinical databases either
      to inform or to evaluate meso-level (organisation and delivery of health care)
      and macro-level (national) policies. Reviewing the use of 15 of the best
      established databases in England, we identify and describe four published
      examples of each use. These show that policy-makers can either make use of the
      data itself or of research based on the database. For evaluating policies, the
      major advantages are the huge sample sizes available, the generalisability of the
      data, its immediate availability and historic information. The principal
      methodological challenges involve the need for risk adjustment and time-series
      analysis. Given their usefulness in the policy arena, there are several reasons
      why national clinical databases have not been used more, some due to a lack of
      'push' by their custodians and some to the lack of 'pull' by policy-makers.
      Greater exploitation of these valuable resources would be facilitated by policy
      makers' and custodians' increased awareness, minimisation of legal restrictions
      on data use, improvements in the quality of databases and a library of examples
      of applications to policy.

PMID- 23116631
TI  - Pathways towards chronic care-focused healthcare systems: evidence from Spain.
AB  - Increasing healthcare expenditure is a matter of concern in many countries,
      particularly in relation to the underlying drivers of such escalation that
      include ageing, medical innovation, and changes in the burden of disease, such as
      the growing prevalence of chronic diseases. Most healthcare systems in developed
      countries have been designed to 'cure' acute episodes, rather than to 'manage'
      chronic conditions, and therefore they are not suitably or efficiently organized
      to respond to the changing needs and preferences of users. New models of chronic
      care provision have been developed to respond to the changing burden of disease
      and there is already considerable practical experience in several different
      countries showing their advantages but also the difficulties associated with
      their implementation. In this paper, we focus on the Spanish experience in terms
      of policy changes and pilot studies focused on testing the feasibility of moving
      towards chronic care models. In particular, we discuss a framework that
      identifies and analyses ten key prerequisites to achieving high performing
      chronic care-based healthcare systems and apply it to the current Spanish
      National Health System (NHS). We find that the design of the Spanish NHS already
      meets some of these pre-requisites. However, other features are still in their
      early stages of development or are being applied only in limited geographical and
      clinical contexts. We outline the policies that are being implemented and the
      pathway that the Spanish NHS is taking to address the crucial challenge of the
      transition towards an optimal health system focused on chronic care. Given the
      current evidence and trends, we expect that the pathway for developing a
      chronicity strategy being followed by the Spanish NHS will significantly
      transform its current healthcare delivery model in the next few years.

PMID- 23116633
TI  - Cutaneous drug reactions.

PMID- 23116634
TI  - An unusual clandestine laboratory synthesis of 3,4-methylenedioxyamphetamine
      (MDA).
AB  - An unknown compound from a putative clandestine laboratory was analyzed by GC-MS,
      GC-IRD, IR (ATR), and NMR and found to be alpha-methyl-3,4
      methylenedioxyphenylpropionamide (MMDPPA), an unusual precursor for the synthesis
      of 3,4-methylenedioxyamphetamine (MDA), a Schedule I controlled substance. A
      portion of this precursor was subjected to the Hofmann Degradation (i.e., Hofmann
      Rearrangement) reaction using a sodium hypochlorite solution (bleach) to produce
      the expected compound, MDA. When excess hypochlorite was used in the reaction, a
      second, unexpected, compound was formed. Use of the listed instrumentation
      identified the new material as 2-chloro-4,5-methylenedioxyamphetamine, a compound
      not previously identified in the forensic literature.

PMID- 23116635
TI  - Methamphetamine and amphetamine concentrations in survivors of body-packer
      syndrome in Japan.
AB  - There are few reports from Japan on the analysis of fluids in survivors of body
      packer syndrome. We analyzed the concentrations of stimulants in the serum,
      plasma and urine collected from three patients suspected of being body packers at
      immigration that were referred to hospitals between 2010 and 2011. The drugs were
      extracted with solid-phase columns and analyzed by gas chromatography-mass
      spectrometry (GC-MS). In all cases, wrapped, cylindrical packets of foreign
      bodies were detected in the intestinal tract on plain X-ray (X-P) and computed
      tomography (CT), and they were eventually removed surgically. In case 1, the
      patient presented with convulsions and tachycardia at admission to the hospital
      and one of the packets was found to have ruptured. In case 2, although the
      subject appeared to have an intestinal obstruction caused by the packets on the
      third day, he exhibited no symptoms on arrival and the packets did not appear to
      have ruptured. In case 3, the patient exhibited restlessness on the first day and
      one of the removed packets had ruptured. In all cases, methamphetamine (MA) and
      amphetamine (AP) were detected in serum, plasma and urine. In this study, we
      report the variation in MA and AP concentrations in survivors of body-packer
      syndrome. The serum and plasma concentrations of MA were high in subjects that
      exhibited symptoms of MA intoxication. MA and AP were also detected in the case
      in which the patient exhibited no symptoms of intoxication and the packets had
      not ruptured. These results suggest either that the stimulants may have seeped
      through the wrap of the packets, or that the subject had been abusing the drugs.

PMID- 23116636
TI  - Comparative analysis of ORF5 nucleotide sequences and amino acid sequences of the
      GP5 protein of equine arteritis virus (EAV) detected in the semen of stallions
      from Eastern Poland.
AB  - The purpose of this study was to conduct a comparative analysis of the ORF5 gene
      fragment nucleotide sequences and the GP5 protein amino acid sequences formed on
      this matrix, for the equine arteritis virus (EAV) strains isolated from the semen
      of infected stallions from Eastern Poland. The study covered 41 stallions whose
      blood serum tested positive for antigens specific to the EAV. The presence of EAV
      genetic material was shown in material from 5 horses, in one of which permanent
      presence of viral RNA was detected over the entire 4-year study period (the
      material was sampled four times at yearly intervals). The mutual similarity among
      the ORF5 nucleotide sequences of EAV obtained in our own studies was 90.7-99%,
      whereas their similarity to a sequence of an isolate of the PL1 virus, determined
      in Polish horses previously, was 76.6-83%. A comparison of the primary structure
      of capsid glycoprotein encoded by the analysed section of ORF5 showed that amino
      acid substitution happens most frequently in region V1 of GP5, between positions
      61 and 121. A phylogenetic analysis of our own isolates with sequences of viruses
      isolated from horses from the USA, Europe and New Zealand (available in the gene
      bank), made it possible to determine that the majority of the detected strains of
      the pathogen can be classified into the European group, with the Austrian strain
      of EAV as its protoplast.

PMID- 23116637
TI  - Baicalin attenuates proinflammatory cytokine production in oxygen-glucose
      deprived challenged rat microglial cells by inhibiting TLR4 signaling pathway.
AB  - Baicalin, a flavonoid compound isolated from Scutellariae radix, has been shown
      to possess a number of pharmacological effects. The aim of the present study was
      to observe the inhibitory effects of baicalin on the activation of microglial
      cells induced by oxygen-glucose deprivation (OGD) and the specific mechanisms by
      which these effects are mediated. Cultured rat primary microglial cells were
      exposed to baicalin at final concentrations of 10 MUg/ml, 20 MUg/ml and 40 MUg/ml
      during 4h of OGD. The effects of baicalin on (i) cell viability; (ii) secretion
      of proinflammatory cytokines; (iii) Tlr4 mRNA expression; (iv) p-c-jun, p-ERK1/2,
      p-JNK, p-p38, TRAF6 and p-IkappaB-alpha levels; and (v) co-localization of TLR4
      and MyD88 were evaluated using the Cell Counting Kit-8 (CCK-8), enzyme-linked
      immunosorbent assays (ELISA), reverse transcription-polymerase chain reaction (RT
      PCR), western blot and double-labeled immunofluorescence staining, respectively.
      OGD increased cell viability and release of TNF-alpha, IL-1beta, IL-6 and IL-8,
      these effects were suppressed by baicalin. Baicalin also attenuated the OGD
      induced increases in Tlr4 mRNA expression. In addition, high dose of baicalin
      reduced TRAF6 levels remarkably. Furthermore, baicalin also downregulated
      phosphorylation of IkappaB-alpha, c-jun, ERK1/2, JNK, p38 and inhibited the OGD
      induced transfer of MyD88 from cytoplasm to membrane in microglial cells. The
      results show that baicalin can inhibit OGD-induced production of inflammatory
      factors in microglial cells by attenuating inflammatory factors and regulating
      the TLR4 signaling pathways.

PMID- 23116638
TI  - Protective effect of low molecular fraction of MGN-3, a modified arabinoxylan
      from rice bran, on acute liver injury by inhibition of NF-kappaB and JNK/MAPK
      expression.
AB  - D-Galactosamine (GalN) induces acute hepatitis in experimental animals; this
      hepatitis has been shown to be suppressed by oral or intraperitoneal
      administration of modified arabinoxylan from rice bran (MGN-3), and active low
      molecular fraction isolated from MGN-3 (LMW). We previously reported that this
      protective mechanism is mediated in part by downregulation of interleukin-18 (IL
      18). The present study shows for the first time that nuclear factor-kappaB (NF
      kappaB), mitogen-activated protein kinase (MAPK) and CD14 are involved in the
      suppressive action of LMW on GalN-induced hepatitis. Wistar rats (aged 4 weeks,
      SLC) were intraperitoneally treated with either MGN-3 or LMW. Then, rats were
      given GalN at 400mg/kg at 1h after the initial treatment. The serum activity of
      transaminases (ALT and AST) was significantly higher after GalN treatment; these
      changes were attenuated by MGN-3 and LMW. Furthermore, LMW abrogated inhibitor of
      kappaB kinase (IkappaB) degradation induced by GalN, and this was associated with
      the inhibition of NF-kappaB activation. Moreover, phosphorylated stress-activated
      protein kinase/c-Jun N-terminal kinase (JNK) protein expression in the liver
      after GalN treatment was significantly higher, and LMW reduced this increase. We
      also found that GalN treatment induced TLR4 and CD14 mRNA expression, and LMW
      significantly inhibited CD14 mRNA expression. These results suggest that the
      suppressive effects of LMW on GalN-induced hepatitis are possibly related to
      inhibition of NF-kappaB, JNK phosphorylation and CD14 expression.

PMID- 23116639
TI  - Inflammation-based prognostic system predicts survival after surgery for stage IV
      colorectal cancer.
AB  - BACKGROUND: The aim of this study was to estimate whether the Glasgow prognostic
      score (GPS) is useful for predicting the survival of patients after surgery for
      stage IV colorectal cancer (CRC). METHODS: The GPS was calculated on the basis of
      admission data as follows: patients with both an increased C-reactive protein
      (CRP) level (>1.0 mg/dL) and hypoalbuminemia (<3.5 g/dL) were allocated a score
      of 2, and patients showing one or none of these abnormalities were allocated a
      score of 1 or 0, respectively. RESULTS: A total of 108 patients with stage IV CRC
      were enrolled. Although multivariate analyses showed that tumor pathology,
      subclass of stage IV CRC, and the GPS were associated with overall survival, the
      GPS could divide the patients into 3 independent groups showing significant
      differences in postoperative survival (P = .018). CONCLUSIONS: The GPS is not
      only one of the most significant clinical characteristics associated with the
      overall survival of patients with stage IV CRC, but also a useful indicator that
      is capable of dividing such patients into 3 independent groups before surgery.

PMID- 23116640
TI  - Outcomes and complications after splenectomy for hematologic disorders.
AB  - BACKGROUND: Splenectomy is generally a second-line therapy in patients with
      immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AHA)
      refractory to medical therapy. Our objective was to evaluate outcomes after
      splenectomy for these disorders. METHODS: A retrospective review of the medical
      records of patients who underwent splenectomy for ITP or AHA from January 1,
      1996, to December 31, 2010 was completed. RESULTS: Sixty patients met the study
      criteria: 45 with ITP and 15 with AHA. The mean age was 49.4 +/- 21.7 years; 63%
      were women. Initially, 91% and 93% of ITP and AHA patients experienced a complete
      response (P = .999); however, 17% of ITP and 29% of AHA patients relapsed (P =
      .443). Sixty-four percent of patients responded after relapse for a complete
      response rate of 85% (82% in ITP and 93% in AHA, P = .427). Thirty-day and long
      term complication rates were 10% and 5%, respectively. There were no splenectomy
      related 30-day mortalities. CONCLUSIONS: Splenectomy for ITP and AHA resulted in
      favorable response rates with low morbidity and is an effective adjunct in the
      management course of patients failing to achieve or sustain responses with
      medical therapy.

PMID- 23116641
TI  - Arginine vasopressin significantly increases the rate of successful organ
      procurement in potential donors.
AB  - BACKGROUND: Hormone replacement therapy increases the number and quality of
      grafts recovered from brain-dead organ donors. Arginine vasopressin (AVP) has
      also been shown to have beneficial effects. The aim of this study was to
      determine the effect of AVP on recovery rates. METHODS: The Organ Procurement and
      Transplantation Network database was used. Donors treated with hormone
      replacement therapy and vasopressor agents who were successfully procured between
      January 1, 2009, and June 30, 2011, were studied. AVP-positive and AVP-negative
      donors were compared. The primary study end point was the rate of high-yield
      procurement (>=4 organs). RESULTS: A total of 10,431 donors were included. AVP
      was infused in 7,873 (75.5%) and was associated with an increased rate of high
      yield procurement (50.5% vs 35.6%, P < .001). There was less overall graft
      refusal due to poor function (38.9% vs 45.6%, P < .001). AVP independently
      predicted high yield procurement. CONCLUSIONS: The use of AVP with hormone
      replacement therapy is independently associated with an increased rate of organ
      recovery. This strategy should be universally adopted in the management of donors
      progressing to neurologic death.

PMID- 23116642
TI  - Platycodin D attenuates bile duct ligation-induced hepatic injury and fibrosis in
      mice.
AB  - Platycodin D (PD) is the major triterpene saponin in the root of Platycodon
      grandiflorum. The aim of the present study was to evaluate the protective effects
      of PD on bile duct ligation (BDL)-induced cholestasis in mice. Mice were
      allocated to five groups: sham, BDL alone, and BDL with PD treatment at 1, 2, and
      4mg/kg. PD was administered to the mice for 28 consecutive days after the BDL
      operation. PD treatment of BDL-operated mice decreased serum alanine
      aminotransferase, serum aspartate aminotransferase, and total bilirubin levels by
      up to 37%, 31%, and 41%, respectively, in comparison with the levels in mice that
      underwent BDL alone. PD treatment attenuated oxidative stress, as evidenced by an
      increase in anti-oxidative enzyme levels glutathione and superoxide dismutase
      together with a decrease in lipid peroxidation and oxidative stress indices
      levels of malondialdehyde and nitric oxide. Histopathological studies further
      confirmed the protective effects of PD on cholestasis-induced hepatic injury and
      liver fibrosis in mice. In addition, nuclear factor-kappa B and inducible nitric
      oxide synthase levels significantly decreased after PD treatment, as did the
      levels of hepatocyte apoptosis. Taken together, these results suggest that PD
      treatment might be beneficial in cholestasis-induced hepatotoxicity.

PMID- 23116643
TI  - Rosmarinic acid ameliorates acute liver damage and fibrogenesis in carbon
      tetrachloride-intoxicated mice.
AB  - The aim of this study was to investigate the therapeutic potential of rosmarinic
      acid (RA), a natural phenolic, in the treatment of acute liver toxicity. RA at
      10, 25 and 50mg/kg was administered by gavage once daily for 2 consecutive days,
      6h after CCl(4) intoxication. CCl(4) intoxication caused hepatic necrosis and
      increased serum ALT activity. In the livers, oxidative/nitrosative stress was
      evidenced by increased 3-nitrotyrosine (3-NT) and thiobarbituric acid reactive
      substances (TBARS) formation and a significant decrease in Cu/Zn superoxide
      dismutase (SOD) activity. CCl(4) administration triggered inflammatory response
      in mice livers by activating nuclear factor-kappaB (NF-kappaB), which coincided
      with the induction of tumor necrosis factor-alpha (TNF-alpha) and cyclooxygenase
      2 (COX-2). RA improved histological and serum markers of liver damage and
      significantly ameliorated oxidative/nitrosative stress and inflammatory response
      in liver tissue. Additionally, RA prevented transforming growth factor-beta1 (TGF
      beta1) and alpha-smooth muscle actin (alpha-SMA) expression, suggesting
      suppression of profibrotic response. Furthermore, RA significantly inhibited the
      CCl(4)-induced apoptosis, which was evident from decreased cleavage of caspase-3.
      The hepatoprotective activity of RA coincided with enhanced NF-E2-related factor
      2 (Nrf2) and heme oxygenase-1 (HO-1) expression. The results of this study
      indicates that RA possesses antioxidant, anti-inflammatory, antiapoptotic and
      antifibrotic activity against acute liver toxicity.

PMID- 23116644
TI  - A proposed method of goniometric measurement of the dart-throwers motion.
AB  - In recent years, the dart-throwing motion (DTM) has been described in the
      literature as the movement pattern in the wrist where many functional activities
      occur. As therapists, we are trained in measuring wrist flexion, extension,
      radial deviation, and ulnar deviation, but measuring the DTM has not been
      described. This author describes a method for measuring the DTM in the clinic. 
      Victoria Priganc, PhD, OTR, CHT, CLT, Practice Forum Editor.

PMID- 23116645
TI  - The effectiveness of early mobilization after tendon transfers in the hand: a
      systematic review.
AB  - STUDY DESIGN: Systematic review. INTRODUCTION: Over the past decade, early
      mobilization (initiated within a week) has become an increasing trend in
      postoperative rehabilitation after tendon transfer surgery in the hand. However,
      there are no published reviews summarizing the effectiveness of early
      mobilization protocols in comparison with conventional immobilization in tendon
      transfer rehabilitation. PURPOSE: To systematically review available evidence on
      the effectiveness of early mobilization protocols to conventional immobilization
      protocol after tendon transfers in the hand. METHODS: A literature search of the
      Cochrane Library, PubMed, PEDro, EMBASE, and CINAHL databases was conducted (1980
      to date). Randomized controlled trials (RCTs), case-control, and other study
      designs were included. Six articles were eligible for inclusion in the analysis
      (five RCTs and one retrospective study) and 260 articles that did not meet
      inclusion criteria were excluded. Level of evidence (Center for Evidence-based
      Medicine) and methodological quality (Structured Effectiveness Quality Evaluation
      Scale [SEQES] score) of each study were assessed by two independent reviewers.
      RESULTS: This review found three high quality trials (SEQES score: 35-43 of 48),
      with level 1b and 2b evidence, supporting early mobilization of tendon transfers.
      The literature reports reduced total cost, total rehabilitation time, and
      demonstrates that early mobilization is a safe approach with no incidence of
      tendon ruptures or insertion pull out. In the initial phase of rehabilitation,
      outcomes like range of motion, grip strength, pinch strength, total active motion
      of digits, deformity correction, and tendon transfer integration were
      significantly superior with early mobilization compared with immobilization.
      However, in the long term, these outcomes were similar in both the groups,
      suggesting that early mobilization protocol improves hand function in the initial
      phase of rehabilitation (four weeks) and the long-term results (two months to one
      year) are equivalent to immobilization. CONCLUSIONS: Based on a limited number of
      small studies, there is evidence of short-term benefit for early mobilization,
      but inconclusive findings for longer-term outcomes. Until the body of evidence
      increases, clinicians should consider the clinical context, their experience in
      optimizing patient outcomes after surgery, and the patient's preferences when
      selecting between early and late mobilization after tendon transfer. LEVEL OF
      EVIDENCE: 2a.

PMID- 23116646
TI  - Comparison of stepwise addition of prandial insulin to a basal-bolus regimen when
      basal insulin is insufficient for glycaemic control in type 2 diabetes: results
      of the OSIRIS study.
AB  - AIM: The metabolic efficacy of adding prandial insulin in a stepwise manner to a
      straightforward basal-bolus regimen was compared in patients with type 2 diabetes
      mellitus (T2DM), suboptimally controlled by oral antidiabetic drugs (OADs) and
      once-daily basal insulin. METHODS: In this international randomized, parallel
      group, non-inferiority study, 811 patients with poorly controlled type 2 diabetes
      using basal insulin were switched to insulin glargine (GLAR) for 6 months while
      continuing OADs. Patients with HbA(1c) > 7% and FPG < 120 mg/dL (n=476) were then
      randomized to either group 1, GLAR+metformin (MET)+3*insulin glulisine (GLU),
      group 2, GLAR+MET+1-3*GLU, or group 3, GLAR+MET+insulin secretagogue (IS)+1
      3*GLU, for 12 months. Objectives were to show the non-inferiority of efficacy of
      group 2 vs group 1 and vs group 3. Non-inferiority of group 2 vs group 1 was
      concluded if the upper limit of the 95% confidence interval (CI) for the HbA(1c)
      difference was <= to 0.4%. RESULTS: The adjusted HbA(1c) difference of group 2 vs
      1 for the per-protocol population crossed the non-inferiority margin (0.228, 95%
      CI: -0.018-0.473). There was significantly less weight gain in group 2 compared
      with group 1, but adverse events were otherwise similar between the two groups.
      In patients with HbA(1c) < 8% at baseline, non-inferiority was achieved in group
      2 vs group 1. CONCLUSION: Although non-inferiority was not achieved, stepwise
      intensification of GLU added to GLAR showed efficacy close to that of the basal
      bolus approach and with significantly less weight gain.

PMID- 23116647
TI  - Determination of the appropriate catheter length and place for needle
      thoracostomy by using computed tomography scans of pneumothorax patients.
AB  - INTRODUCTION: The primary goal of this study was to compare the chest wall
      thicknesses (CWT) at the 2nd intercostal space (ICS) at the mid-clavicular line
      (MCL) and 5th ICS at the mid-axillary line (MAL) in a population of patients with
      a CT confirmed pneumothorax (PTX). This result will help physicians to determine
      the optimum needle thoracostomy (NT) puncture site in patients with a PTX.
      MATERIALS AND METHODS: All trauma patients who presented consecutively to A&E
      over a 12-month period were included. Among all the trauma patients with a chest
      CT (4204 patients), 160 were included in the final analysis. CWTs were measured
      at both sides and were compared in all subgroup of patients. RESULTS: The average
      CWT for men on the 2nd ICS-MCL was 38mm and for women was 52mm; on the other
      hand, on the 5th ICS-MAL was 33mm for men and 38mm for women. On the 2nd ICS-MCL
      17% of men and 48% of women; on the 5th ICS-MAL 13% of men and 33% of women would
      be inaccessible with a routine 5-cm catheter. Patients with trauma, subcutaneous
      emphysema and multiple rib fractures would have thicker CWT on the 2nd ICS-MCL.
      Patients with trauma, lung contusion, sternum fracture, subcutaneous emphysema
      and multiple rib fractures would have thicker CWT on the 5th ICS-MAL.
      CONCLUSIONS: This study confirms that a 5.0-cm catheter would be unlikely to
      access the pleural space in at least 1/3 of female and 1/10 of male Turkish
      trauma patients, regardless of the puncture site. If NT is needed, the 5th ICS
      MAL is a better option for a puncture site with thinner CWT.

PMID- 23116648
TI  - Percutaneous plating for comminuted midshaft fractures of the clavicle: a
      surgical technique to aid the reduction with nail assistance.
AB  - INTRODUCTION: Due to the complex anatomy of the clavicle, percutaneous plating
      with indirect reduction for comminuted midshaft fracture of the clavicle is
      challenging. The aim of this series was to report on a novel technique of nail
      assisted percutaneous plating and to evaluate the radiographic and clinical
      outcomes in comminuted midshaft fractures of the clavicle. MATERIALS AND METHODS:
      Between 2009 and 2010, with nail assistance for the reduction and its
      maintenance, percutaneous plating was performed in 14 patients with comminuted
      midshaft fracture of the clavicle. The mean follow-up period was 17.6 months
      (range, 15-31 months). A retrospective review of the clinical and radiologic
      results for these patients was conducted. RESULTS: All fractures healed within a
      mean period of 15.6 weeks (range, 11-18 weeks) without loss of reduction.
      Regarding complications, there was no occurrence of implant failure or infection.
      All patients showed excellent shoulder function, with a mean Constant shoulder
      score of 99, and a mean Disabilities of the Arm, Shoulder and Hand (DASH) score
      of 4.2 (range, 0-22) at the latest follow-up. No significant difference in mean
      proportional length was observed between injured and uninjured clavicles, with a
      mean of 0.4% (range, -1.5% to 2.4%). CONCLUSIONS: Minimally invasive percutaneous
      plating for comminuted midshaft fractures of the clavicle, combining the
      advantages of elastic intramedullary nailing and percutaneous plating, may be a
      good option.

PMID- 23116649
TI  - The Australian Twin Registry as a resource for genetic studies into ophthalmic
      traits.
AB  - The Australian Twin Registry (ATR) is a not-for-profit organization that
      coordinates research involving Australian twins and researchers. The ATR is one
      of the largest volunteer registries of its kind and contains over 33,000 twin
      pairs. The purpose of this review is to provide a broad overview of recent
      ophthalmic studies that have utilized the ATR for recruitment purposes. Such
      studies include the Australian Twin Eye Study (ATES) and the Genes in Myopia
      (GEM) study. The ATES and GEM studies have undertaken studies into the genetic
      influences on a number of ophthalmic traits through the use of heritability
      studies, linkage studies, genome-wide association studies, and candidate gene
      based studies. An overview of these studies is provided in this review, as well
      as a description of the recruitment methodologies for both the ATES and GEM
      studies.

PMID- 23116650
TI  - Pharmacokinetics of oral pimobendan in healthy cats.
AB  - OBJECTIVE: To describe the pharmacokinetics of oral pimobendan in healthy cats.
      ANIMALS: 18 purpose-bred cats. METHODS: In 10 cats, blood samples were collected
      before, and at multiple time points after, a single oral dose of pimobendan (0.28
      +/- 0.04 mg/kg). In 8 cats, blood samples were collected at 3 various time points
      on the first and third days of twice daily oral dosing of pimobendan for a total
      of 7 doses (0.31 +/- 0.04 mg/kg). Plasma concentrations of pimobendan were
      quantified by high pressure liquid chromatography coupled to tandem mass
      spectrometry. RESULTS: A 1-compartment open model with first order absorption in
      and elimination from the central compartment with a lag time best describes the
      disposition of pimobendan. Two cats were removed from final pharmacokinetic
      descriptive analysis due to delayed minimal absorption from gastrointestinal
      adverse effects. After a lag time (0.3 +/- 0.06 h), pimobendan was rapidly
      absorbed (absorption half-life = 0.2 +/- 0.08 h) and eliminated (elimination half
      life = 1.3 +/- 0.2 h). Maximum plasma concentrations (34.50 +/- 6.59 ng/mL) were
      high and were predicted 0.9 h after drug administration. Apparent volume of
      distribution at steady state (per bioavailability) was large (8.2 +/- 2.5 L/kg).
      The multi-dose study showed the pharmacokinetic model to be robust. CONCLUSION:
      When administered a similar dose on a per weight basis, pimobendan has a
      substantially longer elimination half-life and maximal drug plasma concentration
      in cats as compared to those previously reported in dogs.

PMID- 23116651
TI  - Complete atrioventricular block secondary to cardiac lymphoma in a dog.
AB  - Third degree atrioventricular (AV) block was observed in a patient with a roughly
      spherical mass measuring approximately 1 * 1 * 1 cm, visible in the basilar
      portion of the interventricular septum on 2-dimensional transthoracic
      echocardiographic examination. The patient had a brief history of lethargy and
      episodic collapse, and the owner elected to euthanize the dog after the mass
      lesion was discovered. Necropsy revealed multiple masses within the
      interventricular septum, ventricular free walls and atrial myocardium. The final
      diagnosis was large cell (T-cell) lymphosarcoma.

PMID- 23116652
TI  - 2-Hydroxyestradiol enhances binge onset in female rats and reduces prefrontal
      cortical dopamine in male rats.
AB  - Women are more likely to suffer from a bingeing-related eating disorder, which is
      surprising, since estradiol reduces meal size and is associated with reduced
      binge frequency. This apparent contradiction may involve the estradiol
      metabolite, 2-hydroxyestradiol. We previously reported that female rats had
      faster escalations in shortening intake during the development of bingeing than
      did males, but acute administration of 2-hydroxyestradiol increased the intake of
      vegetable shortening to a greater extent in male rats once bingeing was
      established. Here, we report two separate studies that follow up these previous
      findings. In the first, we hypothesized that chronic exposure to 2
      hydroxyestradiol would promote escalation of bingeing during binge development in
      ovariectomized female rats. In the second, we hypothesized that acute exposure to
      2-hydroxyestradiol would enhance dopamine signaling in the prefrontal cortex
      after bingeing was established in male rats. In study 1, non-food-deprived female
      rats were separated into 3 groups: ovariectomized (OVX) with chronic 2
      hydroxyestradiol supplementation (E), OVX with vehicle supplementation (O), and
      intact with vehicle (I). Each group was given access to an optional source of
      dietary fat (shortening) on Mon, Wed, and Fri for 4 weeks. 2-hydroxyestradiol
      supplementation prevented OVX-induced weight gain and enhanced escalation of
      shortening intake over the four-week period (ps<0.05). Additionally, in week 4,
      rats in the E group ate significantly more shortening than I controls, less chow
      than either the O or I group, and had a higher shortening to chow ratio than O or
      I (ps<0.05). Study 2 indicated that acute injection of 2-hydroxyestradiol
      abolished shortening-evoked dopamine efflux in the prefrontal cortex of bingeing
      male rats (p<0.05). Together, these studies indicate that 2-hydroxyestradiol can
      exacerbate bingeing as it develops and can suppress dopamine signaling in the
      prefrontal cortex once bingeing is established.

PMID- 23116653
TI  - Tuberculin skin test conversion among health sciences students: a retrospective
      cohort study.
AB  - Previous studies have reported that health sciences students are at greater risk
      for tuberculosis infection, especially in developing countries. The objective of
      this study was to estimate the prevalence, incidence, and factors associated with
      latent tuberculosis infection among Health Sciences students in Peru. Students
      enrolled at private university (in Lima-Peru) are tested annually for
      tuberculosis infection by tuberculin skin test. Data on tuberculin skin test
      results between 2002 and 2009 was used in this retrospective cohort study, a
      total of 4842 students were included. Tuberculin skin test conversion was defined
      as the change of tuberculin skin test from negative (<10 mm) to positive (>=10
      mm) after 48-72 h of inoculation. Baseline tuberculin skin test positivity was
      1.0% (95%CI: 0.6%-1.3%), whereas tuberculin skin test conversion incidence was
      12.4 per 100 person-years (95%CI: 11.8-13.0). This study showed that students
      from clinical careers in close contact with patients had an increased risk of
      tuberculosis infection in the internship, especially Medicine, Dentistry, Medical
      Technology and Nursing. Administrative, environmental and personal protection
      measures should be implemented and evaluated periodically in order to reduce the
      risk of exposure.

PMID- 23116654
TI  - The feasibility of a telephone coaching program on heart failure home management
      for family caregivers.
AB  - OBJECTIVES: To test the feasibility of delivery and evaluate the helpfulness of a
      coaching heart failure (HF) home management program for family caregivers.
      BACKGROUND: The few available studies on providing instruction for family
      caregivers are limited in content for managing HF home care and guidance for
      program implementation. METHOD: This pilot study employed a mixed methods design.
      The measures of caregiver burden, confidence, and preparedness were compared at
      baseline and 3 months post-intervention. Descriptive statistics were used to
      summarize program costs and demographic data. Content analysis research methods
      were used to evaluate program feasibility and helpfulness. RESULTS: Caregiver (n
      = 10) burden scores were significantly reduced and raw scores of confidence and
      preparedness for HF home management improved 3 months after the intervention.
      Content analyses of nurse and caregiver post-intervention data found caregivers
      rated the program as helpful and described how they initiated HF management
      skills based on the program. CONCLUSIONS: The program was feasible to implement.
      These results suggest the coaching program should be further tested with a larger
      sample size to evaluate its efficacy.

PMID- 23116655
TI  - Application of a vasculature model and standardization of the renal hilar
      approach in laparoscopic partial nephrectomy for precise segmental artery
      clamping.
AB  - BACKGROUND: Clamping the segmental renal artery instead of the main renal artery
      during nephron-sparing surgery is a promising technique to decrease warm ischemia
      injury. Understanding vasculature characteristics and adopting an appropriate
      hilar approach to segmental arteries are essential to the technique. OBJECTIVE:
      To study the role of the vasculature model and to standardize the renal hilar
      approach in segmental renal artery dissection during laparoscopic partial
      nephrectomy (LPN). DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of
      a consecutive series of 82 patients who underwent LPN with a precise clamping
      technique from December 2009 to June 2011 with a mean follow-up of 20 mo.
      SURGICAL PROCEDURE: Three-dimensional dynamic renal vascular models were
      established based on dual-source computed tomographic angiography. Clamping
      number, clamping position, and a different hilar approach accessing target
      segmental arteries were determined preoperatively. Target arteries were dissected
      and clamped based on the model. Tumor excision and renorrhaphy were performed
      under regional parenchymal ischemia. OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: Renal vascular characteristics and surgical outcomes were analyzed. The
      outcomes among different surgical approaches were compared using one-way analysis
      of variance test or Fisher exact test. RESULTS AND LIMITATIONS: All surgeries
      were performed successfully without converting to main renal artery clamping or
      radical nephrectomy. The median operative time was 90 min, and the mean clamping
      time was 24 min. The median estimated blood loss (EBL) was 200 ml, and six
      patients received blood transfusions. Five patients had hematuria without any
      intervention. One patient had a postoperative hemorrhage and received selective
      embolization intervention. Statistical analysis showed that appropriate surgical
      approaches chosen from the models led to comparable operative times, EBL, and
      complication rates. The limitation of the study lies on its retrospective
      feature. CONCLUSIONS: A renal vasculature model provides effective orientation
      for a precise clamping technique. A standardized hilar approach based on the
      model optimizes the surgical procedure and leads to satisfactory surgical
      outcomes.

PMID- 23116656
TI  - Will the future of health care lead to the end of the robotic golden years?

PMID- 23116657
TI  - Occlusion angiography using intraoperative contrast-enhanced ultrasound scan
      (CEUS): a novel technique demonstrating segmental renal blood supply to assist
      zero-ischaemia robot-assisted partial nephrectomy.
AB  - BACKGROUND: Recent innovations in technology and operative techniques have
      enabled safe performance of robot-assisted zero-ischaemia partial nephrectomy
      (PN), thus preventing the deleterious effect of warm ischaemia time. OBJECTIVE:
      To describe a novel technique of occlusion angiography using intraoperative
      contrast-enhanced ultrasound scan (CEUS) for zero-ischaemia robot-assisted PN
      (RAPN). DESIGN, SETTING, AND PARTICIPANTS: We used a prospective cohort
      evaluation of five patients who had imaging suspicious of renal cell carcinoma
      (RCC) treated at a single centre. SURGICAL PROCEDURE: We used computed tomography
      with three-dimensional reconstruction to identify renal arterial anatomy and its
      relationship to the tumour. Then, RAPN was performed with selective clamping and
      demonstration of a nonperfused segment of kidney (occlusion angiography) using
      intraoperative CEUS. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We
      prospectively collected data on baseline, perioperative, and postoperative
      parameters. RESULTS AND LIMITATIONS: We describe the effects seen on ultrasound
      contrast administration. Contrast flare is seen in the segment of the kidney that
      is perfused. When selective clamping is performed, a watershed (line of
      demarcation) between the perfused and nonperfused segments of the kidney is
      clearly seen, allowing excision of the tumour in a relatively avascular plane and
      ensuring an adequate oncologic margin, when feasible. The mean age was 68.2 yr of
      age (range: 36-85), and the mean tumour size was 29.6mm (range: 20-42). The mean
      intraparenchymal extension of the tumour was 22.6mm (range: 12-30). Three tumours
      were located on the right kidney and two on the left. The mean blood loss was
      420ml (range: 200-1000). The histology revealed clear cell RCC in two patients,
      oncocytoma in two patients, and type 1 papillary RCC in one patient. All the
      surgical specimens had negative surgical margins. The mean decrease in glomerular
      filtration rate was 8.4ml (range: 0-24). The mean follow-up was 6.4 mo (range: 5
      8), with no evidence of recurrence in any patient. The only limitation in
      adopting this technique is the need for an intraoperative ultrasound probe with a
      CEUS mode. However, most specialists who perform minimally invasive surgery for
      small renal tumours believe that intraoperative ultrasound scan imaging is
      essential to achieving adequate resection margins. CONCLUSIONS: Intraoperative
      CEUS can be a useful adjunct in determining whether zero-ischaemia RAPN is
      feasible by delineating the area of nonperfusion. This technique has several
      advantages over the currently available techniques, such as indigo carmine green
      and Doppler probes.

PMID- 23116658
TI  - Cabazitaxel plus prednisone for metastatic castration-resistant prostate cancer
      progressing after docetaxel: results from the German compassionate-use programme.
AB  - BACKGROUND: Cabazitaxel (Cbz) is an approved second-line treatment in metastatic
      castration-resistant prostate cancer (mCRPC) following docetaxel therapy with a
      significant survival benefit compared with mitoxantrone. However, grade 3/4
      toxicities were reported in 82% of patients. OBJECTIVE: To report on the safety
      results of mCRPC patients treated within a compassionate-use programme in
      Germany. DESIGN, SETTING, AND PARTICIPANTS: A total of 111 patients with a mean
      age of 67.9 yr (range: 49-81 yr) and progressive mCRPC were included. Patients
      had received a mean number of 12.7 +/- 10.8 cycles (range: 6-69 cycles) of
      docetaxel with a mean cumulative dose of 970.9 mg/m(2); mean time from last
      docetaxel application to progression was 6.95 mo (range: 2-54 mo). Of the
      patients, 31.5% progressed by prostate-specific antigen (PSA) increase only; the
      remainder had a combination of PSA increase and clinical progression.
      INTERVENTION: Cbz at a dosage of 25mg/m(2) intravenously every 3 wk combined with
      5mg of oral prednisone twice a day. OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: Treatment-associated toxicity was the primary study end point;
      progression-free and overall survival were secondary end points. A descriptive
      statistical analysis was performed. RESULTS AND LIMITATIONS: Patients received a
      mean number of 6.5 +/- 2.2 cycles of Cbz and a mean cumulative dose of 160.3 +/-
      51.5mg/m(2). Grade 3 and 4 treatment-emergent adverse events were recorded in 34
      patients (30.6%) and 18 patients (16.2%), respectively. Grade 3/4 anaemia,
      neutropenia, and thrombocytopenia were reported in 4.5%, 7.2%, and 0.9% of the
      patients, respectively. Neutropenic fever was reported in 1.8% of the patients.
      Grade 3/4 gastrointestinal toxicity was identified in 4.5% of the patients. Three
      patients died because of Cbz-related toxicity. Granulocyte colony-stimulating
      growth factors were used in 17.1% of patients. The limitations are due to the
      nonrandomised nature of the trial. CONCLUSIONS: Treatment with Cbz is tolerable
      and is associated with a low incidence of serious adverse events in a real-world
      patient population with CRPC. The outcome of serious adverse events can be
      minimised with proactive treatment management and conscientious monitoring.

PMID- 23116659
TI  - Evaluation of the in vitro release and pharmacokinetics of parenteral injectable
      formulations for steroids.
AB  - The aim of this study was to investigate the pharmacokinetics of injectable
      conventional dosage forms containing steroids. First, the in vitro release of
      drospirenone (DRSP) microcrystal suspensions (MCSs) was studied. Next, the
      pharmacokinetics of selected subcutaneously injected DRSP MCSs was analyzed in
      female Wistar rats and Cynomolgus monkeys. Furthermore, in vivo and in vitro
      results were fitted to mathematical models. Although the in vitro-in vivo
      correlation was partially good, the predictability of the in vitro test was
      assumed to be restricted. Nevertheless, mathematical calculations and in vitro
      results allow the interpretation of in vivo results and the identification of
      parameters influencing the drug release. DRSP microcrystal size had a marginal
      influence on the pharmacokinetics. The drug absorption was slower from aqueous
      MCSs than from peanut oil MCSs. Absorption profiles of aqueous DRSP MCSs
      correlated best with Hixson-Crowell model, whereas absorption profiles of oil
      based DRSP MCSs showed a good fit to the Higuchi model. The established
      assumptions were used to interpret the pharmacokinetics of subcutaneously
      injected oil-based formulations of the steroid ZK28. In summary, low drug
      solubility in the vehicle and a high vehicle viscosity were assumed to result in
      slower and constant drug release. 

PMID- 23116660
TI  - Auditory brainstem implant indications.

PMID- 23116661
TI  - IL-15Ralpha deficiency leads to mitochondrial and myofiber differences in fast
      mouse muscles.
AB  - The purpose of this study was to determine mitochondrial changes in fast muscles
      from interleukin-15 receptor alpha knockout (IL-15RalphaKO) mice. We tested the
      hypothesis that fast muscles from IL-15RalphaKO mice would have a greater
      mitochondrial density and altered internal structure compared to muscles from
      control mice. In fast muscles from IL-15RalphaKO mice, mitochondrial density was
      48% greater with a corresponding increase in mitochondrial DNA content. Although
      there were no differences in the relative size of isolated mitochondria, internal
      complexity was lower in mitochondria from IL-15RalphaKO mice. These data support
      an increase in mitochondrial biogenesis and provide direct evidence for a greater
      density and altered internal structure of mitochondria in EDL muscles deficient
      in IL-15Ralpha.

PMID- 23116662
TI  - TNF-alpha and TGF-beta synergistically stimulate elongation of human endothelial
      cells without transdifferentiation to smooth muscle cell phenotype.
AB  - We earlier reported synergy between tumor necrosis factor-alpha (TNF-alpha) and
      transforming growth factor-beta1 (TGF-beta1) for apoptosis in human umbilical
      vein endothelium (HUVEC). Here, we study morphological change by circularity
      measurement of HUVEC surviving this cytokine induced synergistic apoptosis.
      Contrasting with reports by others studying bovine endothelium, HUVEC did not
      change morphology in response to TGF-beta1. TNF-alpha markedly elongated cells
      (p<0.001) and this further increased with combination of the two cytokines
      (p<0.001), while elongation was accompanied by increased actin stress fibres.
      Transdifferentiation of HUVEC to a smooth muscle cell phenotype as reported
      elsewhere was excluded in the current study.

PMID- 23116663
TI  - Regulation of activin A release from murine bone marrow-derived neutrophil
      precursors by tumour necrosis factor-alpha and insulin.
AB  - Activin A, a transforming growth factor-beta family cytokine, plays a crucial
      role in regulating the onset and severity of many inflammatory conditions, such
      as acute lipopolysaccharide (LPS)-induced inflammation. Activin A is also
      implicated in type 2 diabetes (T2D), a disease characterised by insulin
      resistance, hyperglycaemia and chronic elevation of pro-inflammatory cytokines,
      including tumour necrosis factor (TNF-alpha). In the human, neutrophils contain
      activin A that can be released in response to TNF-alpha. Studies of inflammatory
      disease in vivo, however, generally use the mouse, so it is essential to know if
      murine neutrophils have similar properties. Regulation of activin A was
      investigated in bone marrow-derived neutrophil precursors (BMNPs) from 8 to 10
      weeks old C57BL6/J male mice. The BMNPs contained 7-fold higher concentrations of
      activin A than bone marrow mononuclear cells. Release of activin A from isolated
      BMNPs was stimulated by TNF-alpha, but this was not due to increased activin A
      production. In contrast to TNF-alpha, LPS had no effect on isolated BMNPs, but
      stimulated activin A release and production in total bone marrow cell cultures.
      Moreover, activin A release in response to LPS, was not prevented in TNF-alpha
      null mice. Increased glucose and insulin had no effect on base-line activin A
      secretion by BMNPs in culture, but pre-treatment with insulin blocked the TNF
      alpha induced release of activin A. These results indicate that murine
      neutrophils are a source of stored activin A, the release of which can be
      directly stimulated by TNF-alpha, although TNF-alpha is not the only stimulator
      of activin A release during inflammation. Furthermore, regulation of neutrophil
      activin A release by insulin may also play a role in the inflammation associated
      with T2D.

PMID- 23116665
TI  - Random Forest classification based on star graph topological indices for
      antioxidant proteins.
AB  - Aging and life quality is an important research topic nowadays in areas such as
      life sciences, chemistry, pharmacology, etc. People live longer, and, thus, they
      want to spend that extra time with a better quality of life. At this regard,
      there exists a tiny subset of molecules in nature, named antioxidant proteins
      that may influence the aging process. However, testing every single protein in
      order to identify its properties is quite expensive and inefficient. For this
      reason, this work proposes a model, in which the primary structure of the protein
      is represented using complex network graphs that can be used to reduce the number
      of proteins to be tested for antioxidant biological activity. The graph obtained
      as a representation will help us describe the complex system by using topological
      indices. More specifically, in this work, Randic's Star Networks have been used
      as well as the associated indices, calculated with the S2SNet tool. In order to
      simulate the existing proportion of antioxidant proteins in nature, a dataset
      containing 1999 proteins, of which 324 are antioxidant proteins, was created.
      Using this data as input, Star Graph Topological Indices were calculated with the
      S2SNet tool. These indices were then used as input to several classification
      techniques. Among the techniques utilised, the Random Forest has shown the best
      performance, achieving a score of 94% correctly classified instances. Although
      the target class (antioxidant proteins) represents a tiny subset inside the
      dataset, the proposed model is able to achieve a percentage of 81.8% correctly
      classified instances for this class, with a precision of 81.3%.

PMID- 23116664
TI  - Contribution of membrane permeability and unstirred layer diffusion to nitric
      oxide-red blood cell interaction.
AB  - Nitric oxide (NO) consumption by red blood cell (RBC) hemoglobin (Hb) in
      vasculature is critical in regulating the vascular tone. The paradox of NO
      production at endothelium in close proximity of an effective NO scavenger Hb in
      RBCs is mitigated by lower NO consumption by RBCs compared to that of free Hb due
      to transport resistances including membrane resistance, extra- and intra-cellular
      resistances for NO biotransport to the RBC. Relative contribution of each
      transport resistance on NO-RBC interactions is still not clear. We developed a
      mathematical model of NO transport to a single RBC to quantify the contributions
      from individual transport barriers by analyzing the effect of RBC membrane
      permeability (P(m)), hematocrit (Hct) and NO-Hb reaction rate constants on NO-RBC
      interactions. Our results indicated that intracellular diffusion of NO was not a
      rate limiting step for NO-RBC interactions. The extracellular diffusion
      contributed 70-90% of total transport resistance for P(m)>1 cm s(-1) whereas
      membrane resistance accounts for 50-75% of total transport resistance for
      P(m)<0.1 cm s(-1). We propose a narrow P(m) range of 0.21-0.44 cm s(-1) for 10
      45% Hct, respectively, below which membrane resistance is more significant and
      above which extracellular diffusion is a dominating transport resistance for NO
      RBC interactions.

PMID- 23116666
TI  - Lens culinaris Medik. seed proteome: analysis to identify landrace markers.
AB  - Unlike modern cultivars selected for their growth performances in specific
      environmental conditions, local landraces have a high genetic variability that is
      an important resource for plant breeding. Consequent to their high adaptation to
      different environmental conditions, these landraces may have evolved adaptive
      gene complexes To promote the survival of endangered lentil landraces, we
      previously investigated the genetic relationship between two ancient landraces
      cultivated in the Molise region (Capracotta and Conca Casale, south-central
      Italy) and widely spread commercial varieties using an integrated approach
      consisting of morphological, DNA and protein characterization. In the present
      study, we used a proteomic approach to compare the mature seed proteomes of the
      Capracotta and Conca Casale lentil landraces. Multivariate analysis of 145
      differentially expressed protein spots demonstrated that 52 proteins are required
      to discriminate among the two landraces. Therefore, these 52 proteins can be
      considered "landrace markers". The results of this study show that the
      combination of proteomics and multivariate analysis can be used to identify
      physiological and/or environmental markers, and is thus a powerful tool that
      complements the analysis of biodiversity in plant ecotypes.

PMID- 23116667
TI  - Overexpression of a protein disulfide isomerase-like protein from
      Methanothermobacter thermoautotrophicum enhances mercury tolerance in transgenic
      rice.
AB  - MTH1745, from thermophilic archaea Methanothermobacter thermoautotrophicum, is a
      protein disulfide isomerase-like protein (PDIL) with a chaperone function and
      disulfide isomerase activity. Mercuric cations have a high affinity for
      sulfhydryl groups and consequently inhibit plant growth. Disulfide compounds
      (e.g., copper-zinc superoxide dismutase, Cu/Zn SOD) and sulfhydryl compounds
      (e.g., glutathione, phytochelatins, and metallothioneins) play important roles in
      mercury (Hg) response. To study the relationship between Hg detoxification and
      PDILs, we overexpressed MTH1745 in Oryza sativa L. cv. Nipponbare by
      Agrobacterium-mediated transformation. The transgenic rice seedlings displayed Hg
      tolerance with obvious phenotypes and more effective photosynthesis compared to
      wild-type plants. Furthermore, lower levels of superoxide anion radicals,
      hydrogen peroxide, and malondialdehyde were observed in leaves or roots of
      transgenic plants. Antioxidant enzyme activities of superoxide dismutase and
      peroxidase were notably higher in transgenic seedlings under different
      concentrations of mercuric chloride. Moreover, increased content of non-protein
      thiols, reduced glutathione (GSH), and GSH/GSSG (GSSG, oxidized glutathione)
      ratio were also observed in the detoxification of Hg. These results indicated
      that heterologous expression of a PDIL from extremophiles in rice could protect
      the synthesis, increase stability of proteins, and enhance Hg tolerance in rice.

PMID- 23116670
TI  - Histochemical location of key enzyme activities involved in receptivity and self
      incompatibility in the olive tree (Olea europaea L.).
AB  - Stigma-surface and style enzymes are important for pollen reception, selection
      and germination. This report deals with the histochemical location of the
      activity of four basic types of enzyme involved in these processes in the olive
      (Olea europaea L.). The detection of peroxidase, esterase and acid-phosphatase
      activities at the surface of the stigma provided evidence of early receptivity in
      olive pistils. The stigma maintained its receptivity until the arrival of pollen.
      Acid-phosphatase activity appeared in the style at the moment of anthesis and
      continued until the fertilization of the ovule. RNase activity was detected in
      the extracellular matrix of the styles of flowers just before pollination and
      became especially evident in pistils after self-pollination. This activity
      gradually decreased until it practically disappeared in more advanced stages.
      RNase activity was also detected in pollen tubes growing in pollinated pistils
      and appeared after in vitro germination in the presence of self-incompatible
      pistils. These findings suggest that RNases may well be involved in intraspecific
      pollen rejection in olive flowers. To the best of our knowledge this is the first
      time that evidence of enzyme activity in stigma receptivity and pollen selection
      has been described in this species.

PMID- 23116668
TI  - Technologies for systems-level analysis of specific cell types in plants.
AB  - The study of biological processes at cell type resolution requires the isolation
      of the specific cell types from an organism, but this presents a great technical
      challenge. In recent years a number of methods have been developed that allow
      deep analyses of the epigenome, transcriptome, and ribosome-associated mRNA
      populations in individual cell types. The application of these methods has lead
      to a clearer understanding of important issues in plant biology, including cell
      fate specification and cell type-specific responses to the environment. In this
      review, we discuss current mechanical- and affinity-based technologies available
      for isolation and analysis of individual cell types in a plant. The integration
      of these methods is proposed as a means of achieving a holistic view of cellular
      processes at all levels, from chromatin dynamics to metabolomics. Finally, we
      explore the limitations of current methods and the needs for future technological
      development.

PMID- 23116669
TI  - Defective root growth triggered by oxidative stress is controlled through the
      expression of cell cycle-related genes.
AB  - Reactive oxygen species (ROS) have many functions in aerobic organisms. High
      levels of ROS can have a negative impact on plant cells leading to senescence and
      cell death. ROS accumulates in cells subjected to environmental stress and
      induces a cellular response to this external stimulus. To protect cells from the
      negative impacts of excess ROS, plants also possess a ROS detoxifying system to
      maintain normal ROS levels. The regulation of ROS levels is particularly
      important as ROS also functions as an important signal molecule and can regulate
      plant growth by modulating gene expression. Despite the functional importance of
      ROS signaling, little is known about the molecular mechanisms involved in the
      regulation of gene expression through ROS. Therefore, the present study
      investigated the effect of hydrogen peroxide (H(2)O(2)), a ROS compound, on cell
      cycle-related gene expression. Gene expression analyses coupled with
      microdissected sections of the developmental zone of Arabidopsis root tips
      revealed that H(2)O(2) affects the expression of cell cycle-related genes.
      Additionally, ROS scavenging enzymes were found to play an important role in the
      root growth phenotype induced by H(2)O(2). Specifically, root growth inhibition
      by H(2)O(2) was diminished in transgenic Arabidopis overexpressing peroxidase but
      increased in a catalase2 (cat2) mutant. The strong root growth inhibition
      observed in the cat2 mutant upon H(2)O(2) treatment indicated that CAT2 has an
      essential role in maintaining root meristem activity in the presence of oxidative
      stress. Overall, these results confirm that ROS function not only as stress
      related compounds but that they also function as signaling molecules to regulate
      the progression of the cell cycle in root tips.

PMID- 23116671
TI  - Capsicum annuum WRKY transcription factor d (CaWRKYd) regulates hypersensitive
      response and defense response upon Tobacco mosaic virus infection.
AB  - WRKY transcription factors regulate biotic, abiotic, and developmental processes.
      In terms of plant defense, WRKY factors have important roles as positive and
      negative regulators via transcriptional regulation or protein-protein
      interaction. Here, we report the characterization of the gene encoding Capsicum
      annuum WRKY transcription factor d (CaWRKYd) isolated from microarray analysis in
      the Tobacco mosaic virus (TMV)-P(0)-inoculated hot pepper plants. CaWRKYd belongs
      to the WRKY IIa group, a very small clade in the WRKY subfamily, and WRKY IIa
      group has positive/negative regulatory roles in Arabidopsis and rice. CaWRKYd
      transcripts were induced by various plant defense-related hormone treatments and
      TMV-P(0) inoculation. Silencing of CaWRKYd affected TMV-P(0)-mediated
      hypersensitive response (HR) cell death and accumulation of TMV-P(0) coat protein
      in local and systemic leaves. Furthermore, expression of some pathogenesis
      related (PR) genes and HR-related genes was reduced in the CaWRKYd-silenced
      plants compared with TRV2 vector control plants upon TMV-P(0) inoculation.
      CaWRKYd was confirmed to bind to the W-box. Thus CaWRKYd is a newly identified
      Capsicum annuum WRKY transcription factor that appears to be involved in TMV-P(0)
      mediated HR cell death by regulating downstream gene expression.

PMID- 23116672
TI  - An ornithine delta-aminotransferase gene OsOAT confers drought and oxidative
      stress tolerance in rice.
AB  - Ornithine delta-aminotransferase (delta-OAT) is a pyridoxal-5'-phosphate
      dependent enzyme that has been proposed to be involved in proline (Pro) and
      arginine (Arg) metabolism. However, the actual role of delta-OAT in abiotic
      responses in plants remains to be clarified. Here we characterized an ornithine
      delta-aminotransferase gene OsOAT that confers multi-stress tolerance in rice
      (Oryza sativa). We confirmed that OsOAT is a direct target of the stress
      responsive NAC transcription factor SNAC2. OsOAT is responsive to multiple
      stresses and phytohormone treatments. Both ABA-dependent and ABA-independent
      pathways contributed to the drought-induced expression of OsOAT. Overexpression
      of the OsOAT gene in rice resulted in significantly enhanced drought and osmotic
      stress tolerance. Overexpression of OsOAT caused significantly increased delta
      OAT activity and Pro accumulation under normal growth conditions. In addition,
      OsOAT-overexpressing plants showed significantly increased tolerance to oxidative
      stress. The glutathione (GSH) content and activity of reactive oxygen species
      (ROS)-scavenging enzymes, such as glutathione peroxidase, were also increased in
      OsOAT-overexpressing plants. We conclude that OsOAT is a target gene of SNAC2 and
      confers stress tolerance mainly through enhancing ROS-scavenging capacity and Pro
      pre-accumulation.

PMID- 23116673
TI  - Transcriptional expression of Stilbene synthase genes are regulated
      developmentally and differentially in response to powdery mildew in Norton and
      Cabernet Sauvignon grapevine.
AB  - Stilbenic compounds are natural phytoalexins that have antimicrobial activities
      in plant defense against pathogens. Stilbene synthase (STS) is the key enzyme
      that catalyzes the biosynthesis of stilbenic compounds. Grapevine genome contains
      a family of preliminarily annotated 35 STS genes, the regulation of each STS gene
      needs to be studied to define their roles. In this study, we selected eight STS
      genes, STS8, STS27/31, STS16/22, STS13/17/23, and applied quantitative polymerase
      chain reaction (qPCR) to characterize their transcriptional expression profiles
      in leaf tissues upon infection by the powdery mildew fungus (PM), Erysiphe
      necator (Schw.) Burr. Their transcripts were also compared in young and old
      leaves as well as in the berry skin at five developmental stages in Vitis
      vinifera 'Cabernet Sauvignon' and Vitis aestivalis 'Norton'. The results showed
      that transcripts of selected STS genes increased significantly in Cabernet
      Sauvignon leaves at 24 and 48 h post inoculation with PM spores and remained
      unchanged in Norton leaves in response to the PM infection. Transcripts of STS8,
      STS27/31 and STS13/17/23 were more abundant in the old leaves of Norton than in
      Cabernet Sauvignon. STS genes showed lower expression levels in young leaves than
      in old leaves. Transcript levels of the eight STS genes increased drastically in
      the berry skin of Cabernet Sauvignon and Norton post veraison. In addition, the
      content of trans-resveratrol in the berry skin rapidly increased post veraison
      and reached the highest level at harvest. These assays demonstrated that
      individual STS genes are regulated differentially in response to PM infection and
      during development in the two grape varieties. The present study yields basic
      knowledge for further investigation of the regulation and function of each STS
      gene in grapevine and provides experimental evidences for the functional
      annotation of the STS gene family in the grapevine genome.

PMID- 23116675
TI  - The involvement of PUMP from mitochondria of Araucaria angustifolia embryogenic
      cells in response to cold stress.
AB  - In this study, the responses of plant uncoupling mitochondrial protein (PUMP) and
      alternative oxidase (AOX) in mitochondria from embryogenic cells of A.
      angustifolia subjected to cold stress (4 degrees C for 24 h or 48 h) is reported.
      In the mitochondria of stressed cells, PUMP activity increased by approximately
      45% (at 24h and 48 h), which was determined by measuring the oxygen consumption
      after the addition of linoleic acid and the inhibition by BSA and ATP. PUMP
      activation was confirmed using transmembrane electrical potential (Deltapsi)
      assays. Immunoblot assays showed an increase of PUMP expression by 40% and 150%
      after 24h and 48 h of cold stress, respectively. AOX activity, measured under
      conditions similar to those of the PUMP assays, was only slightly increased in
      the mitochondria from stressed cells (at 24h and 48 h), as demonstrated by oxygen
      consumption experiments. Cell viability was unaffected by cold stress, indicating
      that the effects on PUMP and AOX were not caused by cell death. These results
      show that the main response of this gymnosperm to cold stress is the activation
      of PUMP, which suggests that this protein may be involved in the control of
      reactive oxygen species generation, which has been previously associated with
      this condition.

PMID- 23116674
TI  - Leaf mechanisms for drought resistance in Zizyphus jujuba trees.
AB  - No information exists on the mechanisms developed at the level of leaf water
      relations by pear-jujube trees (Zizyphus jujuba Mill.) to confront drought. For
      this reason, the purpose of the present study was to analyse its leaf water
      relations in order to clarify the resistance mechanisms (avoidance and tolerance)
      developed in response to a water stress and during recovery. Field-grown 7-year
      old pear-jujube trees (cv. Grande de Albatera) were subjected to three irrigation
      treatments. Control (T0) plants were drip irrigated (112% ETo) in order to
      guarantee non-limiting soil water conditions, T1 plants (deficit irrigation, 64%
      ETo) were drip irrigated according to the criteria used by the grower and T2
      plants irrigated as T0 but subjected to water withholding for 36 days and a
      subsequent re-irrigation at the levels used in T0 for 14 days, during the summer
      of 2011. The results indicated that pear-jujube plants confront water stress by
      developing stress avoidance and stress tolerance mechanisms. From the beginning
      of deficit irrigation (T1) and water withholding (T2) to when maximum water
      stress levels were achieved, leaf turgor was maintained allowing substantial gas
      exchange levels and, consequently, good leaf productivity. This leaf turgor
      maintenance was mainly due to two simultaneous and complementary mechanisms. Leaf
      conductance and the duration of maximum stomatal opening in water stressed plants
      decreased in order to control water loss via transpiration, contributing to
      maintain leaf turgor (stress avoidance mechanisms). Also, the gradual recovery of
      g(l) observed after rewatering the plants can be considered as a mechanism for
      promoting leaf rehydration. In addition, from the beginning of the stress period,
      active osmotic adjustment operated, also contributing to the maintenance of leaf
      turgor (stress tolerance mechanism). The high RWC(a) levels and the possibility
      of increasing the accumulation of water in the apoplasm in response to water
      stress, supporting a steeper gradient in water potential between the leaf and the
      soil, which can be considered another drought tolerance characteristic in pear
      jujube.

PMID- 23116676
TI  - Opinion: prospects for improving photosynthesis by altering leaf anatomy.
AB  - Engineering higher photosynthetic efficiency for greater crop yields has gained
      significant attention among plant biologists and breeders. To achieve this goal,
      manipulation of metabolic targets and canopy architectural features has been
      heavily emphasized. Given the substantial variations in leaf anatomical features
      among and within plant species, there is large potential to engineer leaf anatomy
      for improved photosynthetic efficiency. Here we review how different leaf
      anatomical features influence internal light distribution, delivery of CO(2) to
      Rubisco and water relations, and accordingly recommend features to engineer for
      increased leaf photosynthesis under different environments. More research is
      needed on (a) elucidating the genetic mechanisms controlling leaf anatomy, and
      (b) the development of a three dimensional biochemical and biophysical model of
      leaf photosynthesis, which can help pinpoint anatomical features required to gain
      a higher photosynthesis.

PMID- 23116677
TI  - Gene expression analysis in response to low and high temperature and oxidative
      stresses in rice: combination of stresses evokes different transcriptional
      changes as against stresses applied individually.
AB  - Transcript expression profiles of rice seedlings were analyzed in response to (a)
      prior exposure with oxidative stress followed by heat or cold stress and (b)
      simultaneous exposure to oxidative stress along with heat stress or cold stress.
      The numbers of genes differentially regulated during stress combination of cold
      and oxidative stress as well as heat and oxidative stress treatments were higher
      when compared with the number of genes differentially regulated in response to
      individual stress conditions. A large number of transcript changes were noted
      unique to the stress combination mode as compared with when individual stresses
      were applied. Specific differences in the transcript expression profiles of OsHsf
      and OsClp gene family members were noted during combination of stresses as
      against individual stresses. For instance, OsHsf26 induction was specific to
      stress combinations, while OsHsfA2a, OsHsfA2f, and OsHsfA3 transcript levels were
      additively affected during combination of stresses. Unique promoter models and
      transcription factor binding sites (i.e. P$KNOX3_01, P$OSBZ8_Q6) were noted in
      the promoters of differentially regulated genes during combination of stresses.
      It is proposed that stress combinations represent a novel state of abiotic
      stresses for rice seedlings that might involve a different type of molecular
      response.

PMID- 23116678
TI  - A comparison between nuclear dismantling during plant and animal programmed cell
      death.
AB  - Programmed cell death (PCD) is a process of organized destruction of cells,
      essential for the development and maintenance of cellular homeostasis of
      multicellular organisms. Cells undergoing PCD begin a degenerative process in
      response to internal or external signals, whereby the nucleus becomes one of the
      targets. The process of nuclear dismantling includes events affecting the nuclear
      envelope, such as formation of lobes at the nuclear surface, selective
      proteolysis of nucleoporins and nuclear pore complex clustering. In addition,
      chromatin condensation increases in coordination with DNA fragmentation. These
      processes have been largely studied in animals, but remain poorly understood in
      plants. The overall process of cell death has different morphological and
      biochemical features in plants and animals. However, recent advances suggest that
      nuclear dismantling in plant cells progresses with morphological and biochemical
      characteristics similar to those in apoptotic animal cells. In this review, we
      summarize nuclear dismantling in plant PCD, focusing on the similarities and
      differences with their animal counterparts.

PMID- 23116679
TI  - Nucleotide diversity and linkage disequilibrium in antioxidant genes of
      Brachypodium distachyon.
AB  - Brachypodium distachyon (Brachypodium) is a powerful model system for studying
      cereal, bioenergy, forage, and turf grasses. Nucleotide diversity (pi) and
      linkage disequilibrium (LD) in candidate genes involved in the antioxidative
      pathways in this species are not known. The average pi for CAT encoding catalase,
      GPX encoding glutathione peroxidase, DHAR encoding dehydroascorbate reductase,
      MDHAR encoding monodehydroascorbate reductase, and APX ecoding ascorbate
      peroxidase was 0.0027 among 19 accessions contrasting for drought tolerance. The
      highest value of pi was found in APX (0.0046) and the lowest pi was in MDHAR
      (0.0006). The average single nucleotide polymorphism (SNP) frequency across these
      five genes was one SNP per 131 bp between two randomly sampled sequences for the
      five genes in the sequence length ranging from 1,447 bp to 1,701 bp. The LD decay
      was slow and extended to a distance of more than 1.2kb for all genes. The
      neighbor-joining tree analyses of DHAR, MDHAR, and CAT generally separated
      accessions differing in drought tolerance. The results indicate a putative role
      of these candidate genes in increasing general fitness of Brachypodium.

PMID- 23116680
TI  - Feasibility of implementing a practice guideline for fall prevention on geriatric
      wards: a multicentre study.
AB  - BACKGROUND: About 40% of all adverse events in hospital are falls, but only about
      one in three Belgian hospitals have a fall prevention policy in place. The
      implementation of a national practice guideline is urgently needed. OBJECTIVE AND
      DESIGN: This multicentre study aimed to determine the feasibility of a previously
      developed guideline. SETTING, PARTICIPANTS AND METHOD: Seventeen geriatric wards,
      selected at random out of 40 Belgian hospitals who agreed to take part in the
      study, evaluated the fall prevention guideline. After the one-month test period,
      49 healthcare workers completed a questionnaire on the feasibility of the
      guideline. RESULTS: At the end of the study, 512 geriatric patients had been
      assessed using the practice guideline. The average time spent per patient on case
      finding, multifactorial assessment and initiating a treatment plan was 5.1, 76.1
      and 30.6 min, respectively. For most risk assessments and risk modifications,
      several disciplines considered themselves as being responsible and capable. The
      majority (more than 69%) of the respondents judged the practice guideline as
      useful, but only a small majority (62.3%) believed that the guideline could be
      successfully integrated into their daily practice over a longer period of time.
      Barriers for implementation included a large time investment (81.1%), lack of
      communication between the different disciplines (35.8%), lack of motivation of
      the patient (34.0%), lack of multidisciplinary teamwork (28.3%), and lack of
      interest from the hospital management (15.4%). CONCLUSION: Overall, the guideline
      was found useful, and for each risk factor (except for visual impairment), at
      least one discipline felt responsible and capable. Towards future implementation
      of the guideline, following steps should be considered: division of the risk
      factor assessment duties and interventions among different healthcare workers;
      patient education; appointment of a fall prevention coordinator; development of a
      fall prevention policy with support from the management of the hospital.

PMID- 23116681
TI  - The impact of the work environment of nurses on patient safety outcomes: a multi
      level modelling approach.
AB  - BACKGROUND: Patient safety is a priority for health services in all countries.
      The importance of the nurse's role in patient safety has been established.
      Effective nurse staffing levels, nurse education levels, and a positive work
      environment for nurses are factors which are known to impact on patient safety
      outcomes. OBJECTIVES: This study sought to explore the relationship between the
      ward environment in which nurses practice and specific patient safety outcomes,
      using ward level variables as well as nurse level variables. The outcomes were
      nurse-reported patient safety levels in the wards in which they work, and numbers
      of formal adverse events reports submitted by nurses in the last year. DESIGN:
      This cross-sectional quantitative study was carried out within a European FP7
      project: Nurse Forecasting: Human Resources Planning in Nursing (RN4CAST)
      project. SETTINGS: 108 general medical and surgical wards in 30 hospitals
      throughout Ireland. PARTICIPANTS: All nurses in direct patient care in the study
      wards were invited to participate. Data from 1397 of these nurses were used in
      this analysis. METHODS: A nurse survey was carried out using a questionnaire
      incorporating the Practice Environment Scale of the Nursing Work Index (PES-NWI).
      Ethical approval was obtained from the authors' institution and all ethics
      committees representing the 30 study hospitals. Multilevel modelling was carried
      out to examine the impact of ward level factors on patient safety. These included
      proportions of nurses on the ward educated to degree level, and aggregated ward
      level mean for PES-NWI scores. RESULTS: The study results support other research
      findings indicating that a positive practice environment enhances patient safety
      outcomes. Specifically at ward level, factors such as the ward practice
      environment and the proportion of nurses with degrees were found to significantly
      impact safety outcomes. The models developed for this study predicted 76% and 51%
      of the between-ward variance of these outcomes. The results can be used to
      enhance patient safety within hospitals by demonstrating factors at ward-level
      which enable nurses to effectively carry out this aspect of their role.
      CONCLUSIONS: The importance of ward-level nurse factors such as nurse education
      level and the work environment should be recognised and manipulated as important
      influences on patient safety.

PMID- 23116683
TI  - Quality of life analysis in patients with KRAS wild-type metastatic colorectal
      cancer treated first-line with cetuximab plus irinotecan, fluorouracil and
      leucovorin.
AB  - BACKGROUND: In the CRYSTAL study adding cetuximab to first-line FOLFIRI
      significantly improved outcome in patients with KRAS wild-type metastatic
      colorectal cancer. Quality of life (QoL) was assessed, and associations with
      tumour response and survival were investigated. PATIENTS AND METHODS: The
      European Organization for Research and Treatment of Cancer QoL questionnaire-core
      30 was used, focusing on global health status (GHS)/QoL and social functioning
      scales. Radiological response was assessed by an independent review committee.
      RESULTS: QoL was evaluable in 627/666 patients (94%) with KRAS wild-type tumours;
      of these 52% received FOLFIRI, and 48% FOLFIRI plus cetuximab. Pattern mixture
      analysis revealed no significant differences for GHS/QoL (P=0.12) and social
      functioning scores (P=0.43) between the treatment arms. In additional analyses:
      early skin reactions in patients receiving cetuximab did not significantly affect
      these QoL scales, and tumour response was more common (58% versus 40%, P=0.0002)
      and survival longer (Hazard ratio 1.68, P<0.0001) in asymptomatic compared with
      symptomatic patients at baseline. Adding cetuximab to FOLFIRI was associated with
      significantly higher tumour response irrespective of patient baseline symptomatic
      status, and enhanced symptom relief from baseline in those whose tumours had
      responded. CONCLUSION: Adding cetuximab to FOLFIRI improved response rate and
      survival without either improving or negatively impacting on GHS/QoL and social
      functioning.

PMID- 23116682
TI  - The European Society of Breast Cancer Specialists recommendations for the
      management of young women with breast cancer.
AB  - EUSOMA (The European Society of Breast Cancer Specialists) is committed to
      writing recommendations on different topics of breast cancer care which can be
      easily adopted and used by health professionals dedicated to the care of patients
      with breast cancer in their daily practice. In 2011, EUSOMA identified the
      management of young women with breast cancer as one of the hot topics for which a
      consensus among European experts was needed. Therefore, the society recently
      organised a workshop to define such recommendations. Thirteen experts from the
      different disciplines met for two days to discuss the topic. This international
      and multidisciplinary panel thoroughly reviewed the literature in order to
      prepare evidence-based recommendations. During the meeting, two working groups
      were set up to discuss in detail diagnosis and loco-regional and systemic
      treatments, including both group aspects of psychology and sexuality. The
      conclusions reached by the working groups were then discussed in a plenary
      session to reach panel consensus. Whenever possible, a measure of the level of
      evidence (LoE) from 1 (the highest) to 4 (the lowest) degree, based on the
      methodology proposed by the US Agency for Healthcare Research and Quality (AHRQ),
      was assigned to each recommendation. The present manuscript presents the
      recommendations of this consensus group for the management of young women with
      breast cancer in daily clinical practice.

PMID- 23116684
TI  - Validation of the reflux scale in the European Organisation for Research and
      Treatment of Cancer QLQ-OES18.
AB  - BACKGROUND: Gastro-oesophageal reflux disease (GORD) is assessed by two reflux
      symptom items in the oesophageal-specific module (QLQ-OES18) of the health
      related quality of life (HRQL) questionnaire developed by EORTC. This study
      validated such assessment of GORD. METHODS: This validation study included a
      random sample of the Swedish population, aged 40-79years, who completed the QLQ
      OES18 ('test questionnaire') and a more comprehensive reflux questionnaire
      ('standard questionnaire') in 2008. In the 'test questionnaire', GORD was defined
      using two cut-offs for reflux symptoms experienced during the last week.
      'Definition 1' represented responses 'quite a bit' or more reflux symptoms and
      'definition 2' represented 'a little' or more reflux symptoms. The 'standard
      questionnaire' assessed GORD during the last 3months. RESULTS: Among 6969 invited
      individuals, 4910 (70.5%) responded to both questionnaires. There were generally
      good correlations between the responses to the individual reflux items in the
      comparison questionnaires. Compared to the 'standard questionnaire', 'definition
      1' of GORD in the 'test questionnaire' showed high positive predictive value
      (0.81), high negative predictive value (0.93) and high specificity (0.99), but
      low sensitivity (0.32); while 'definition 2' of GORD rendered low positive
      predictive value (0.39), high negative predictive value (0.98), moderate
      specificity (0.85) and moderate sensitivity (0.83). CONCLUSIONS: The assessment
      of GORD in the QLQ-OES18 questionnaire would benefit from adding items and
      assessing a longer period of history of reflux symptoms and its treatment. As it
      stands, the choice of cut-off for the response alternatives strongly influences
      the specificity and sensitivity of the GORD assessment.

PMID- 23116685
TI  - Synthesis, properties, and reactivity of a series of non-heme {FeNO}(7/8)
      complexes: implications for Fe-nitroxyl coordination.
AB  - The biochemical properties of nitroxyl (HNO/NO(-)) are distinct from nitric oxide
      (NO). Metal centers, particularly Fe, appear as suitable sites of HNO activity,
      both for generation and targeting. Furthermore, reduced Fe-NO(-)/Fe-HNO or
      {FeNO}(8) (Enemark-Feltham notation) species offer unique bonding profiles that
      are of fundamental importance. Given the unique chemical properties of {FeNO}(8)
      systems, we describe herein the synthesis and properties of {FeNO}(7) and
      {FeNO}(8) non-heme complexes containing pyrrole donors that display heme-like
      properties, namely [Fe(LN(4)(R))(NO)] (R = C(6)H(4) or Ph for 3; and R = 4,5
      Cl(2)C(6)H(2) or PhCl for 4) and K[Fe(LN(4)(R))(NO)] (R = Ph for 5; R = PhCl for
      6). X-ray crystallography establishes that the Fe-N-O angle is ~155 degrees  for
      3, which is atypical for low-spin square-pyramidal {FeNO}(7) species. Both 3 and
      4 display nu(NO) at ~1700 cm(-1) in the IR and reversible diffusion-controlled
      cyclic voltammograms (CVs) (E(1/2)=~-1.20 V vs. Fc/Fc(+) (ferrocene/ferrocenium
      redox couple) in MeCN) suggesting that the {FeNO}(8) compounds 5 and 6 are stable
      on the CV timescale. Reduction of 3 and 4 with stoichiometric KC(8) provided the
      {FeNO}(8) compounds 5 and 6 in near quantitative yield, which were characterized
      by the shift in nu(NO) to 1667 and ~1580 cm(-1), respectively. While the nu(NO)
      for 6 is consistent with FeNO reduction, the nu(NO) for 5 appears more indicative
      of ligand-based reduction. Additionally, 5 and 6 engage in HNO-like chemistry in
      their reactions with ferric porphyrins [Fe(III)(TPP)X] (TPP =
      tetraphenylporphyrin; X = Cl(-), OTf(-) (trifluoromethanesulfonate anion or
      CF(3)SO(3)(-))) to form [Fe(TPP)NO] in stoichiometric yield via reductive
      nitrosylation.

PMID- 23116686
TI  - Brain lipoma, corpus callosum hypoplasia and polymicrogyria in familial multiple
      lipomatosis.

PMID- 23116687
TI  - L4 to S1 motor neuron degeneration due to T11-T12 disc herniation with normal
      spinal angiography.

PMID- 23116688
TI  - A novel PANK2 gene mutation in a Persian boy: the first report from Iran.

PMID- 23116689
TI  - GRADE guidelines: 13. Preparing summary of findings tables and evidence profiles
      continuous outcomes.
AB  - Presenting continuous outcomes in Summary of Findings tables presents particular
      challenges to interpretation. When each study uses the same outcome measure, and
      the units of that measure are intuitively interpretable (e.g., duration of
      hospitalization, duration of symptoms), presenting differences in means is
      usually desirable. When the natural units of the outcome measure are not easily
      interpretable, choosing a threshold to create a binary outcome and presenting
      relative and absolute effects become a more attractive alternative. When studies
      use different measures of the same construct, calculating summary measures
      requires converting to the same units of measurement for each study. The longest
      standing and most widely used approach is to divide the difference in means in
      each study by its standard deviation and present pooled results in standard
      deviation units (standardized mean difference). Disadvantages of this approach
      include vulnerability to varying degrees of heterogeneity in the underlying
      populations and difficulties in interpretation. Alternatives include presenting
      results in the units of the most popular or interpretable measure, converting to
      dichotomous measures and presenting relative and absolute effects, presenting the
      ratio of the means of intervention and control groups, and presenting the results
      in minimally important difference units. We outline the merits and limitations of
      each alternative and provide guidance for meta-analysts and guideline developers.

PMID- 23116690
TI  - A systematic review finds prediction models for chronic kidney disease were
      poorly reported and often developed using inappropriate methods.
AB  - BACKGROUND: Chronic kidney disease (CKD) is a global health concern that is
      increasing mainly as the result of increasing incidences of diabetes and
      hypertension. Furthermore, if left untreated, individuals with CKD may progress
      to end-stage kidney failure. Identifying individuals with undiagnosed CKD or
      those who are at an increased risk of developing CKD or progressing to end-stage
      kidney disease (ESKD) is therefore an important challenge. We sought to
      systematically review and critically assess the conduct and reporting of methods
      used to develop risk prediction models for predicting the risk of having
      undiagnosed (prevalent) or future risk of developing (incident) CKD or end-stage
      kidney failure in adults. METHODS: We conducted a systematic search of PubMed
      database to identify studies published up until September 2011 that describe the
      development of models combining two or more variables to predict the risk of
      prevalent or incident CKD or ESKD. We extracted key information that describes
      aspects of developing a prediction model, including the study design, data
      quality, sample size and number of events, outcome definition, risk predictor
      selection and coding, missing data, model-building strategies, and aspects of
      performance. RESULTS: Eleven studies describing the development of 14 prediction
      models were included. Eight studies reported the development of 11 models to
      predict incident CKD or ESKD, whereas 3 studies developed models for prevalent
      CKD. A total of 97 candidate risk predictors were considered, and 43 different
      risk predictors featured in the 14 prediction models. A method, not recommended
      to select risk predictors for inclusion in the multivariate model, using
      statistical significance from univariate screening was carried out in six
      studies. Missing data were frequently poorly handled and reported with no mention
      of missing data in four studies; 4 studies explicitly excluded individuals with
      missing data, and only 2 studies used multiple imputation to replace missing
      values. CONCLUSION: We found that prediction models for chronic kidney were often
      developed using inappropriate methods and were generally poorly reported. Using
      poor methods can affect the predictive ability of the models, whereas inadequate
      reporting hinders an objective evaluation of the potential usefulness of the
      model.

PMID- 23116691
TI  - Pesticide induced immunotoxicity in humans: a comprehensive review of the
      existing evidence.
AB  - The immune system can be the target of many chemicals, with potentially severe
      adverse effects on the host's health. In Western countries pesticides, together
      with new and modified patterns of exposure to chemicals, have been implicated in
      the increasing prevalence of diseases associated with alterations of the immune
      response, such as hypersensitivity reactions, certain autoimmune diseases and
      cancers. Xenobiotics may initiate, facilitate or exacerbate pathological immune
      processes, resulting in immunotoxicity by induction of mutations in genes coding
      for immunoregulatory factors, modifying immune tolerance and activation pathways.
      The purpose of this article is to update the evidence of pesticide
      immunotoxicity. Even if experimental data as well as sporadic human studies
      indicate that some pesticides can affect the immune system, overall, existing
      epidemiological studies are inadequate to raise conclusions on the immunotoxic
      risk associated to pesticide exposure. The available studies on the effects of
      pesticides on human immune system have several limitations including poor
      indication on exposure levels, multiple chemical exposures, heterogeneity of the
      approach, and difficulty in giving a prognostic significance to the slight
      changes often observed. Further studies are necessary, and they should be
      preferably carried out through comparison of pre and post-exposure findings in
      the same group of subjects with a matched control group. Attempt should be made
      to define the prognostic significance of slight changes often observed. Animal
      and in vitro studies are also important and necessary to scientifically support
      epidemiological evidences on pesticide-induced immunotoxicity.

PMID- 23116692
TI  - Model based period analysis of absolute and relative survival with R: data
      preparation, model fitting and derivation of survival estimates.
AB  - Period analysis is increasingly employed in analyses of long-term survival of
      patients with chronic diseases such as cancer, as it derives more up-to-date
      survival estimates than traditional cohort based approaches. It has recently been
      extended with regression modelling using generalized linear models, which
      increases the precision of the survival estimates and enables to assess and
      account for effects of additional covariates. This paper provides a detailed
      presentation how model based period analysis may be used to derive population
      based absolute and relative survival estimates using the freely available R
      language and statistical environment and already available R programs for period
      analysis. After an introduction of the underlying regression model and a
      description of the software tools we provide a step-by-step implementation of two
      regression models in R and illustrate how estimates and a test for trend over
      time in relative survival may be derived using data from a population based
      cancer registry.

PMID- 23116693
TI  - Analysis of time-course gene expression profiles of a periodontal ligament tissue
      model under compression.
AB  - OBJECTIVE: We recently reported establishment of a periodontal ligament (PDL)
      tissue model, which may mimic the biological behaviour of human PDL under static
      compression in orthodontic tooth movement (OTM). In the present study, we aimed
      at investigating the time-course gene expression profiles of the PDL tissue model
      under compression. DESIGN: The PDL tissue model was established through 3-D
      culturing human PDL cells (PDLCs) in a thin sheet of porous poly lactic-co
      glycolic acid (PLGA) scaffolds, which was subjected to 25g/cm(2) static
      compression for 6, 24 and 72h respectively. After that, its gene expression
      profiles were investigated using microarray assay, followed by signalling pathway
      and gene ontology (GO) analysis. Real-time RT-PCR verification was done for 15
      identified genes of interest. The cell proliferation alteration was detected
      through EdU labelling. RESULTS: (1) Among the genes identified as differentially
      expressed, there were numerous osteoclastogenesis inducers (including CCL20, COX
      1, COX-2, RANKL, PTHrP, IL-11, IL-8, etc.), osteoclastogenesis inhibitors
      (including IL-1Ra, NOG, OPG, etc.), and other potential bone remodelling
      regulators (including STC1, CYR61, FOS, etc.). (2) According to analysis of the
      microarray data, the most significant pathways included Cytokine-cytokine
      receptor interaction (containing CCL20, RANKL, IL-11, IL-8, etc.), MAPK
      (containing FGF7, FOS, MAP3K8, JUN, etc.) and Cell cycle (containing CDK1, CCNA2,
      etc.); the most significant GOs included Cell-cell signalling (containing CCL20,
      STC1, FGF7, PTHrP, IL-11, IL-8, etc.), Extracellular space (containing CCL20, IL
      1Ra, NOG, PTHrP, IL-11, IL-8, etc.) and Microtubule-based movement (containing
      KIF11, KIF23, etc.). (3) After prolonged compression, cell proliferation was
      significantly inhibited. CONCLUSION: The present findings have expanded our
      understandings to the roles that PDL plays under static compression in OTM.

PMID- 23116694
TI  - Mutations to A/Puerto Rico/8/34 PB1 gene improves seasonal reassortant influenza
      A virus growth kinetics.
AB  - It is desirable for influenza vaccine virus strains to have phenotypes that
      include good growth and hemagglutinin (HA) protein yield. The quality of these
      characteristics varies among the vaccine viruses and is usually due to multigenic
      effects. Many influenza A virus vaccine viruses are made as reassortants of the
      high yield virus A/Puerto Rico/8/34 (PR/8) and a circulating seasonal virus. Co
      infection of eggs with the two viruses, and selection of reassortants with the HA
      and neuraminidase (NA) segments from the seasonal virus, can result in viruses
      that contain a mixture of internal genes derived from both the high yield virus
      and the circulating virus. Segment 2 (PB1), which encodes the RNA-dependent RNA
      polymerase, frequently cosegregates with the seasonal HA and NA segments. We
      asked whether mutations based on the seasonal PB1 genes could improve vaccine
      virus strains. Here we report that mutations to the PR/8 PB1 gene, based on
      differences observed between seasonal and PR/8 PB1 genes, accelerate egg and cell
      culture based replication for a reassortant virus containing HA and NA segments
      from the low yield A/Wyoming/03/2003 (H3N2) vaccine virus.

PMID- 23116695
TI  - Influenza vaccination coverage among patients and healthcare workers in a
      university hospital during the 2006-2007 influenza season.
AB  - Despite years of public health effort to increase vaccine uptake among
      populations recommended for influenza vaccination, immunization rates remain low
      among patients and healthcare workers (HCWs). The objective of this study was to
      report on influenza vaccination coverage of patients and HCWs for the same time
      period in 4 wards of a university hospital. A prospective cross-sectional study
      was conducted among patients and HCWs between December 11, 2006 and April 15,
      2007 and individual factors associated with being vaccinated against influenza
      were assessed. Results indicated that older patients were significantly more
      vaccinated than younger patients. Physicians and residents were more likely to be
      vaccinated that the rest of staff, with possible differences between wards.
      Immunization of HCWs is a major issue in infection control in hospitals and long
      term care facilities. However, the impact of influenza vaccination among HCWs in
      reducing hospital-acquired influenza and patient morbidity needs to be explored
      further.

PMID- 23116696
TI  - Characterisation of antibody responses in pigs induced by recombinant oncosphere
      antigens from Taenia solium.
AB  - Recombinant antigens cloned from the oncosphere life cycle stage of the cestode
      parasite Taenia solium (T. solium) have been proven to be effective as vaccines
      for protecting pigs against infections with T. solium. Previous studies have
      defined three different host protective oncosphere antigens, TSOL18, TSOL16 and
      TSOL45. In this study, we evaluated the potential for combining the antigens
      TSOL16 and TSOL18 as a practical vaccine. Firstly, in a laboratory trial, we
      compared the immunogenicity of the combined antigens (TSOL16/18) versus the
      immunogenicity of the antigens separately. Secondly, in a field trial, we tested
      the ability of the TSOL16/18 vaccine to induce detectable antibody responses in
      animals living under environmental stress and traditionally reared in areas where
      T. solium cysticercosis is endemic; and finally, we characterised the immune
      response of the study population. Pigs of 8-16 weeks of age were vaccinated with
      200 MUg each of TSOL16 and TSOL18, plus 5mg of Quil-A. Specific total IgG, IgG(1)
      and IgG(2) antibody responses induced by TSOL16 and TSOL18 were determined with
      ELISA. The immunogenicity of both antigens was retained in the combined TSOL16/18
      vaccine. The combined vaccine TSOL16/18 induced detectable specific anti-TSOL18
      antibody responses in 100% (113/113) and specific anti-TSOL16 in 99% (112/113) of
      the vaccinated animals measured at 2 weeks following the booster vaccination.
      From the two IgG antibody subtypes analysed we found there was stronger response
      to IgG(2).

PMID- 23116697
TI  - Insect cell-expressed hemagglutinin with CpG oligodeoxynucleotides plus alum as
      an adjuvant is a potential pandemic influenza vaccine candidate.
AB  - Vaccination is the most effective method used to reduce the morbidity and
      mortality of influenza infections. However, as exemplified in the current swine
      origin influenza virus (S-OIV) pandemic, the global manufacturing capacity of
      influenza vaccines is severely limited. In the present proof-of-concept study, we
      combined cell substrate selection and antigen engineering with adjuvant
      development to design a potential pandemic influenza vaccine candidate, in which
      CpG oligodeoxynucleotides (CpG-ODN) plus alum was used as a composite adjuvant to
      enhance the immunogenicity of insect cell-expressed recombinant hemagglutinin
      (rHA). Our candidate vaccine was found to be effective in inducing protective
      humoral as well as cellular immunity in mice and able to protect the immunized
      mice from related influenza virus challenge. If this candidate vaccine is
      validated in humans, vaccine development can be started immediately after the
      release of the first HA sequence of any pandemic influenza virus. Moreover, given
      the potential of large-scale manufacturing capacity of the recombinant antigen,
      in combination with the antigen-sparing effect of the composite adjuvant, this
      technology could be an invaluable asset in the fight against pandemic influenza.

PMID- 23116698
TI  - Synthesis and biological evaluation of novel 6-substituted analogs of 1alpha,25
      dihydroxy-19-norvitamin D3.
AB  - We have recently described the synthesis and biological evaluation of 1alpha,25
      dihydroxy-6-methylvitamin D3 which binds the vitamin D receptor (VDR) very
      effectively. Unfortunately, this compound has a strong tendency to rearrange to
      its previtamin form. Taking this into consideration, we decided to synthesize a
      series of 6-substituted analogs of 1alpha,25-dihydroxy-19-norvitamin D3 which
      lack the exomethylene moiety at C-10 and thus are unable to undergo a conversion
      to their respective previtamin forms. The synthesis of analogs bearing different
      substituents at C-6 was accomplished by Suzuki-Miyaura cross-coupling reaction of
      a bicyclic organoboron derivative (CD-ring fragment) with the respective alkenyl
      halides (A-ring synthons). The biological in vitro studies of the affinity of
      synthesized analogs to the full-length recombinant rat VDR indicate that presence
      of a bulky, polar substituent at C-6 results in decrease in binding ability.
      Moreover, introduction of a 6-methyl substituent into the 1alpha,25-dihydroxy-19
      norvitamin D3 molecule results in the 9 times lower affinity of the homolog to
      the VDR while the same modification of calcitriol has not influenced binding
      activity. This article is part of a Special Issue entitled 'Vitamin D Workshop'.

PMID- 23116699
TI  - [Do anesthetic techniques influence postoperative outcomes? Part I].
AB  - The influence of anesthetic technique on postoperative outcomes has opened a wide
      field of research in recent years. High-risk patients undergoing non-cardiac
      surgery are those who have higher incidence of postoperative complications and
      mortality. A proper definition of this group of patients should focus maximal
      efforts and resources to improve the results. In view of the significant
      reduction in postoperative mortality and morbidity in last 20 years,
      perioperative research should take into account new indicators to investigate the
      role of anesthetic techniques on postoperative outcomes. Studies focused on the
      evaluation of intermediate outcomes would probably discriminate better
      effectiveness differences between anesthetic techniques. We review some of the
      major controversies arising in the literature about the impact of anesthetic
      techniques on postoperative outcomes. We have grouped the impact of these
      techniques into 9 major investigation areas: mortality, cardiovascular
      complications, respiratory complications, postoperative cognitive dysfunction,
      chronic postoperative pain, cancer recurrence, postoperative nausea/vomiting,
      surgical outcomes and resources utilization. In this first part of the review, we
      discuss the basis on postoperative outcomes research, mortality, cardiovascular
      and respiratory complications.

PMID- 23116700
TI  - Congenital megaprepuce: a 12-year experience (52 cases) of this specific form of
      buried penis.
AB  - OBJECTIVE: Congenital megaprepuce is a specific form of buried penis. Children
      affected by this malformation usually suffer from a subjective difficulty in
      voiding which is the main indication for early surgical correction. The aim of
      this study was to report a single center's 12-year experience in the treatment of
      megaprepuce in children, describing the surgical procedure we used to treat it
      and the results. PATIENTS AND METHODS: We retrospectively reviewed the charts of
      all children who underwent congenital megaprepuce repair between January 1999 and
      August 2011 in our institution. Fifty-two children were operated during the study
      period. Our single surgical technique, not an original one, consists of fixing
      the penile shaft at the base of the penis, and widely reducing the inner prepuce.
      RESULTS: Four children (8%) underwent revision surgery but according to our
      criteria a very good result was observed in only 23 patients, and a less good but
      still acceptable result in 25 patients. CONCLUSION: Our 12-year experience in the
      surgical treatment of congenital megaprepuce demonstrated satisfying results from
      a safe and simple surgical technique, but to achieve the optimum result remains
      difficult.

PMID- 23116701
TI  - Two-phase model for prediction of cell-free layer width in blood flow.
AB  - This study aimed to develop a numerical model capable of predicting changes in
      the cell-free layer (CFL) width in narrow tubes with consideration of red blood
      cell aggregation effects. The model development integrates to empirical relations
      for relative viscosity (ratio of apparent viscosity to medium viscosity) and core
      viscosity measured on independent blood samples to create a continuum model that
      includes these two regions. The constitutive relations were derived from in vitro
      experiments performed with three different glass-capillary tubes (inner
      diameter=30, 50 and 100 MUm) over a wide range of pseudoshear rates (5-300 s(
      1)). The aggregation tendency of the blood samples was also varied by adding
      Dextran 500 kDa. Our model predicted that the CFL width was strongly modulated by
      the relative viscosity function. Aggregation increased the width of CFL, and this
      effect became more pronounced at low shear rates. The CFL widths predicted in the
      present study at high shear conditions were in agreement with those reported in
      previous studies. However, unlike previous multi-particle models, our model did
      not require a high computing cost, and it was capable of reproducing results for
      a thicker CFL width at low shear conditions, depending on aggregating tendency of
      the blood.

PMID- 23116702
TI  - Impact of a multidisciplinary staff meeting on the quality of antibiotherapy
      prescription for bone and joint infections in orthopedic surgery.
AB  - INTRODUCTION: We studied the impact of a weekly multidisciplinary staff meeting
      (MSM) on the quality of antibiotherapy for bone and joint infections in
      orthopedic surgery, as part of professional practice assessment. MATERIALS AND
      METHODS: We retrospectively studied the file of patients hospitalized for bone
      and joint infection. We compared antibiotherapy compliance to good use
      (bacteriology, dose, length of treatment, length of adaptation to microbiology),
      and outcome at six months for patients with bone and joint infections, before
      (March 2007 to March 2009) and after (March 2009 to March 2011) implementation of
      the multidisciplinary staff meeting. We identified 28 patient files (32
      infections) before MSM and 26 patient files (28 infections) after MSM. RESULTS:
      Antibiotherapy was adapted in 47% of cases before MSM, versus 96% after
      (P<0.0001). The dose was optimum in 72% of infections before MSM, versus 89%
      after (P=0.11) and the length of antibiotherapy complied with recommendations in
      41% of infections before MSM, versus 86% after (P=0.0005). The average time of
      antibiotic adaptation to the antibiogram changed from 2 days before MSM to 1.7
      days after (P=0.43). Forty seven per cent of patients were cured at six months
      before MSM, versus 57% after (P=0.45); the rate of treatment failure at six
      months decreased from 25% before MSM to 18% after (P=0.75). CONCLUSION: The
      effectiveness of antibiotherapy significantly improved concerning the spectrum
      and treatment duration (P <= 0.0005) after implementing MSMs in orthopedic
      surgery. But the clinical impact at six months was not significant due to the
      small population sample.

PMID- 23116703
TI  - Rhino-orbito-cerebral mucormycosis: five cases.
AB  - INTRODUCTION AND OBJECTIVE: Mucormycosis is an invasive fungal infection usually
      observed in immunocompromised patients. Mucormycosis is rapidly fatal without an
      early diagnosis and treatment. We report five patients of rhino-orbital-cerebral
      mucormycosis and a literature review. DESIGN: The medical records of five
      patients presenting with rhino-orbital-cerebral mucormycosis, admitted between
      January 1995 and December 2007, were analyzed. All patients underwent tissue
      biopsy. The histologic sections revealed the presence of non-septate hyphae of
      the order Mucorales. RESULTS: The five patients, three men and two women, between
      27 and 61 years of age, were all diabetic. The main symptoms were exophthalmia
      (five patients), facial swelling (four patients), periorbital cellulitis (four
      patients), and cranial nerve palsy (four patients). Anterior rhinoscopy revealed
      palatine or nasal necrotic lesions in four patients. All presented with diabetic
      ketoacidosis and CT scan revealed rhino-orbital-cerebral involvement in every
      patient. All patients were given intravenous amphotericin B. Four patients
      underwent surgical debridement of necrotic tissue. Two patients survived.
      CONCLUSIONS: Mucormycosis is usually a fatal infection in diabetic patients.
      Early diagnosis should be based on imaging data and histology. Amphotericin B
      must be rapidly initiated and associated with aggressive surgical debridement to
      reduce mortality.

PMID- 23116704
TI  - Sport and infectious risk: a systematic review of the literature over 20 years.
AB  - The development of sports activities promoted as a health factor should not hide
      the increased risk for diseases, more particularly infections. A review of
      articles made over the last 20 years was made with a descriptive epidemiological
      purpose. The most marked risk is skin infection with methicillin-resistant
      community acquired Staphylococcus aureus (27.4% of the articles), followed by
      Tinea corporis and capitis (13.7%), and leptospirosis (11.7%). The risk of blood
      borne infection seems low, and articles are rare (3.9%). The risk of disease with
      respiratory transmission (measles, meningococcal meningitis) must be taken into
      account. The effect of physical activity on the immune system depends on the type
      and duration of the work out: it seems to be beneficial for a workout of a
      moderate intensity, and deleterious for a sustained acute work out, or a period
      of intensive training. These periods of protection or susceptibility to
      infections are described as "open window" and "J curve". The only recommendations
      for prevention of sport-related infections arise from the frequency of skin
      infections and the severity of blood-borne infections. These recommendations are
      published by American and international sports authorities. The specificity of
      athletes' management is due to imperatives of competitiveness (maintaining
      physical performance) and the necessity of temporary eviction from sports, in
      case of contagiousness. The athletes must make sure their recommended
      vaccinations are up-to-date.

PMID- 23116705
TI  - Predictive value of the eosinophil counts in the biological diagnosis of
      lymphatic filariasis in French Polynesia.
AB  - SETTINGS: Lymphatic filariasis is common in many tropical and subtropical areas
      and is a major public health issue in south Pacific islands. In endemic areas,
      most infected individuals are asymptomatic but may harbor microfilariae or
      filarial antigens in their peripheral blood. Microscopy remains the reference
      diagnostic tool for the identification of microfilariae but is weakly sensitive.
      The diagnosis of Wuchereria bancrofti infection was dramatically altered by the
      development of filarial antigen tests, which are easy to perform but expensive
      for routine use. Lymphatic filariasis is responsible for acquired eosinophilia
      and blood eosinophil count is commonly used as a screening tool in endemic areas.
      METHOD: We retrospectively analyzed all the results of eosinophil counts, antigen
      and microfilariae detection performed in our laboratory over a 24-month period.
      We calculated the prevalence of antigenemia for various eosinophilic cut offs.
      RESULTS: The prevalence of antigenemia was estimated at 25.78% with eosinophilia
      defined as a count eosinophilic PMN above 500 per mm(3). DISCUSSION: Our
      prevention strategy against lymphatic filariasis is based on annual mass drug
      administration, vector control, and systematic treatment of antigenemic and
      microfilaremic patients. Antigenemic and microfilaremic detection cannot be
      routinely performed because of their cost. Current treatments used for lymphatic
      filariasis are safe and cheaper than antigenic detection. A possible additional
      strategy to decrease the prevalence of antigenemia would be the systematic
      treatment of patients with hypereosinophilia.

PMID- 23116706
TI  - 5-Aminoimidazole-4-carboxamide ribonucleoside stabilizes low density lipoprotein
      receptor mRNA in hepatocytes via ERK-dependent HuR binding to an AU-rich element.
AB  - OBJECTIVE: 5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR) has pleiotropic
      and beneficial effects on metabolic disorders. However, the effects of AICAR on
      low density lipoprotein (LDL) metabolism are poorly understood. METHODS AND
      RESULTS: AICAR induces increased LDLR mRNA levels and increased LDLR protein
      production in hepatocytes. The AICAR-dependent LDLR mRNA increase was partially
      mediated by mRNA stabilization in an extracellular signal-regulated kinase1/2
      (ERK1/2)-dependent manner, but not by the AMP-activated protein kinase (AMPK)
      activation. Reporter assays using a variety of constructs harboring the 3'
      untranslated region (UTR) of human LDLR mRNA revealed that the most upstream AU
      rich element (ARE) was critical for these AICAR effects. Using UV cross-linking
      assays, we found increased binding of three cytoplasmic proteins to this ARE
      region in response to AICAR and identified a 35-kDa protein as Human antigen R
      (HuR). Blocking ERK signaling pathway activation resulted in attenuated HuR
      binding. Silencing HuR expression by RNA interference hindered AICAR-induced LDLR
      mRNA stability, whereas its overexpression stabilized this mRNA. CONCLUSIONS:
      AICAR-dependent LDLR mRNA stabilization is mediated, at least in part, by HuR
      binding to the ARE1 region. Given that AICAR enhanced LDL uptake in hepatocytes,
      our findings warrant further studies using animal models to develop a novel LDL
      cholesterol lowering agent as a possible strategy to treat atherosclerosis
      related cardiovascular diseases.

PMID- 23116707
TI  - Analysis of S-nitrosothiols via copper cysteine (2C) and copper cysteine-carbon
      monoxide (3C) methods.
AB  - This chapter summarizes the principles of RSNO measurement in the gas phase,
      utilizing ozone-based chemiluminescence and the copper cysteine (2C)+/-carbon
      monoxide (3C) reagent. Although an indirect method for quantifying RSNOs, this
      assay represents one of the most robust methodologies available. It exploits the
      NO detection sensitivity of ozone based chemiluminescence, which is within the
      range required to detect physiological concentrations of RSNO metabolites.
      Additionally, the specificity of the copper cysteine (2C and 3C) reagent for
      RSNOs negates the need for sample pretreatment, thereby minimizing the likelihood
      of sample contamination (false positive results), or the loss of certain highly
      labile RSNO species. Herein, we outline the principles of this methodology,
      summarizing key issues, potential pitfalls and corresponding solutions.

PMID- 23116708
TI  - Mass spectrometry-based identification of S-nitrosocysteine in vivo using organic
      mercury assisted enrichment.
AB  - Protein S-nitrosylation is considered as one of the molecular mechanisms by which
      nitric oxide regulates signaling events and protein function. The present review
      presents an updated method which allows for the site-specific detection of S
      nitrosylated proteins in vivo. The method is based on enrichment of S
      nitrosylated proteins or peptides using organomercury compounds followed by LC
      MS/MS detection. Technical aspects for determining the reaction and binding
      efficiency of the mercury resin that assists enrichment of S-nitrosylated
      proteins are presented and discussed. In addition, emphasis is given to the
      specificity of the method by providing technical details for the generation of
      four chemically distinct negative controls. Finally it is provided an overview of
      the key steps for generation and evaluation of mass spectrometry derived data. 

PMID- 23116709
TI  - 1,25-Dihydroxyvitamin D3 inhibits directly human osteoclastogenesis by down
      regulation of the c-Fms and RANK expression.
AB  - OBJECTIVE: 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is a key molecule to maintain
      calcium homeostasis and bone metabolism. It was recently reported that
      1,25(OH)2D3 directly inhibited osteoclast differentiation in mouse bone marrow
      cells and human bone marrow-derived colony-forming unit granulocyte macrophage
      (CFU-GM) cells. However, the direct effects of 1,25(OH)2D3 and its affecting
      mechanisms on the osteoclast differentiation of human osteoclast precursors
      remain largely unknown. In this study, we examined the direct effects of
      1,25(OH)2D3 on the osteoclastogenesis of human peripheral blood (PB) osteoclast
      precursors. METHODS: In vitro osteoclastogenesis assays were performed using
      osteoclast precursors from normal PB. The gene expressions were analyzed using
      real-time PCR. The cell surface proteins, including c-Fms and RANK, were measured
      by flow cytometry. RESULTS: 1,25(OH)2D3 strongly inhibited osteoclast
      differentiation and it suppressed the expression of RANK in the human PB
      osteoclast precursors. One mechanism of RANK inhibition by 1,25(OH)2D3 is down
      regulation of the M-CSF receptor c-Fms, which is required for the expression of
      RANK. In contrast to the previous reports on mouse osteoclast precursors,
      1,25(OH)2D3 did not affect the expression of c-Fos. Parallel to the inhibition of
      osteoclastogenesis, 1,25(OH)2D3 increased the expression and phosphorylation of
      CCAAT enhancer-binding protein beta (C/EBPbeta), which is a recently discovered
      inhibitor of osteoclastogenesis. CONCLUSIONS: Our results show that 1,25(OH)2D3
      inhibits human osteoclastogenesis by decreasing the RANK+ osteoclast precursors,
      and we suggest that 1,25(OH)2D3 may be a powerful therapeutic agent for treating
      inflammation-induced bone disease that shows excessive osteoclast activation.

PMID- 23116710
TI  - Mast cells and inflammation.
AB  - The prominent role for mast cells in the inflammatory response has been
      increasingly well documented in recent years. Mast cells not only contribute to
      maintain homeostasis via degranulation and to generate IgE-mediated allergic
      reactions, but also sit at a major crossroads for both innate and adaptive immune
      responses. The part played by mast cells in chronic inflammatory diseases such as
      rheumatoid arthritis and multiple sclerosis identifies mast cells as a valuable
      treatment target in these diseases. Tyrosine-kinase inhibitors targeting the c
      Kit mast cell receptor have been found effective in treating rheumatoid
      arthritis, asthma, and multiple sclerosis. When used in combination with other
      available drugs, tyrosine-kinase inhibitors may improve the therapeutic
      management of these diseases.

PMID- 23116711
TI  - Jacalin domain in wheat jasmonate-regulated protein Ta-JA1 confers agglutinating
      activity and pathogen resistance.
AB  - Ta-JA1 is a jacalin-like lectin from wheat (Triticum aestivum) plants. To date,
      its homologs are only observed in the Gramineae family. Our previous experiments
      have demonstrated that Ta-JA1 contains a modular structure consisting of an N
      terminal dirigent domain and a C-terminal jacalin-related lectin domain (JRL) and
      this protein exhibits a mannose-specific lectin activity. The over-expression of
      Ta-JA1 gene provides transgenic plants a broad-spectrum resistance to diseases.
      Here, we report the differential activities of the dirigent and JRL domains of Ta
      JA1. In vitro assay showed that the recombinant JRL domain could effectively
      agglutinate rabbit erythrocytes and pathogen bacteria Pseudomonas syringe pv
      tabaci. These hemagglutination activities could be inhibited by mannose but not
      by galactose. In contrast, the recombinant dirigent domain did not show
      agglutination activity. Corresponding to these differentiations of activities,
      similar to full-length of Ta-JA1, the over-expression of JRL domain in transgenic
      plants also increased resistance to the infection of P. syringe. Unlike JRL, the
      over-expression of dirigent domain in transgenic plants led to alteration of the
      seedling sensitivity to salts. In addition, a d(N)/d(S) ratio analysis of Ta-JA1
      and its related proteins showed that this protein family functionally limited to
      a few crop plants, such as maize, rice and wheat.

PMID- 23116713
TI  - Novel chondrogenic and chondroprotective effects of the natural compound harmine.
AB  - A significant number of natural compounds have been shown to regulate the
      behavior of the cells, in collaboration with cellular proteins. CCN2/connective
      tissue growth factor (CTGF) has been reported to have essential roles in
      cartilage development, chondrocyte proliferation and differentiation as well as
      regulation of the extracellular matrix metabolism. Previous studies demonstrated
      the capability of CCN2 to regenerate surgical defects in articular cartilage of
      rat knee. Also, transgenic mice over-expressing cartilage-specific CCN2 were
      shown to be more resistant to aging-related cartilage degradation. We
      hypothesized that small molecules that induce CCN2 in chondrocytes could be novel
      candidates to increase the resistance to aging-related cartilage degradation, or
      even to correct cartilage degenerative changes incurred in OA. Therefore, this
      study screened a compound library and identified the beta-carboline alkaloid
      harmine as a novel inducer of CCN2 in human chondrocytic HCS-2/8 cells and
      osteoarthritic articular chondrocytes. Harmine increased the expression of the
      cartilage markers aggrecan and COL2alpha1, as well as that of the master
      regulator of chondrogenesis, SOX-9. Moreover, harmine notably induced
      chondrogenesis of prechondrocytic ATDC5 cells in micromass cultures. The
      chondroprotective effect of harmine was investigated under inflammatory condition
      by stimulation with TNFalpha, and harmine was shown to ameliorate TNFalpha
      induced decrease in expression of CCN2 and cartilage markers. These findings
      uncover novel chondrogenic effects of harmine and indicate harmine as a potential
      drug for prevention and/or repair of cartilage degradation.

PMID- 23116712
TI  - Antibacterial and leishmanicidal activities of temporin-SHd, a 17-residue long
      membrane-damaging peptide.
AB  - Temporins are a family of short antimicrobial peptides (8-17 residues) that
      mostly show potent activity against Gram-positive bacteria. Herein, we
      demonstrate that temporin-SHd, a 17-residue peptide with a net charge of +2
      (FLPAALAGIGGILGKLF(amide)), expressed a broad spectrum of antimicrobial activity.
      This peptide displayed potent antibacterial activities against Gram-negative and
      Gram-positive bacteria, including multi-drug resistant Staphylococcus aureus
      strains, as well as antiparasitic activity against promastigote and the
      intracellular stage (amastigote) of Leishmania infantum, at concentration not
      toxic for the macrophages. Temporin-SHd that is structured in a non-amphipathic
      alpha-helix in anionic membrane-mimetic environments, strongly and selectively
      perturbs anionic bilayer membranes by interacting with the polar head groups and
      acyl region of the phospholipids, with formation of regions of two coexisting
      phases: one phase rich in peptide and the other lipid-rich. The disruption of
      lipid packing within the bilayer may lead to the formation of transient pores and
      membrane permeation/disruption once a threshold peptide accumulation is reached.
      To our knowledge, Temporin-SHd represents the first known 17-residue long
      temporin expressing such broad spectrum of antimicrobial activity including
      members of the trypanosomatidae family. Additionally, since only a few shorter
      members (13 residues) of the temporin family are known to display antileishmanial
      activity (temporins-TA, -TB and -SHa), SHd is an interesting tool to analyze the
      antiparasitic mechanism of action of temporins.

PMID- 23116714
TI  - Shape string: a new feature for prediction of DNA-binding residues.
AB  - Protein-DNA interactions are involved in many biological processes essential for
      gene expression and regulation. To understand the molecular mechanisms of protein
      DNA recognition, it is crucial to analyze and identify DNA-binding residues of
      protein-DNA complexes. Here, we proposed a novel descriptor shape string and
      another two related features shape string PSSM and shape string pair composition
      to characterize DNA-binding residues. We employed the new features and the
      position-specific scoring matrix (PSSM) for modeling and prediction. The results
      of a benchmark dataset showed that our approach significantly improved the
      accuracy of the predictor. The overall accuracy of our approach reached 85.86%
      with 85.02% sensitivity and 86.02% specificity. The results also demonstrated
      that shape string is a powerful descriptor for the prediction of DNA-binding
      residues. The additional two related features enhanced the predictive value.

PMID- 23116715
TI  - Polyomavirus inactivation - a review.
AB  - Polyomavirus inactivation has been studied since the 1950s when it became
      apparent that certain polio vaccines were contaminated with SV40. Relatively high
      temperatures (>=70  degrees C) are required to effect thermal inactivation of the
      polyomaviruses. The chemical inactivants that are effective (beta-propiolactone,
      ethanol, sodium hydroxide, and formaldehyde) are those that have displayed
      efficacy for other small, non-enveloped viruses, such as the circoviruses. Low pH
      inactivation can be effective, especially at pH at or below 3 and at higher
      temperatures. Polyomaviruses are more resistant to UV-C irradiation than are
      other small non-enveloped viruses such as the parvoviruses and caliciviruses. The
      efficacy of photodynamic inactivation of polyomaviruses is very much dye
      dependent, with toluidine blue, acridine orange, and methylene blue dyes being
      effective photosensitizers. Ionizing radiation can be effective, depending on the
      conditions employed and the inactivation matrix. Inactivation of the oncogenic
      properties of the polyomaviruses may require higher doses of inactivant than
      those required to inactivate infectivity. While the polyomaviruses are considered
      to be highly resistant to inactivation, the degree of resistance is dependent
      upon the specific approach under consideration. For certain approaches, such as
      UV-C and gamma-irradiation, the polyomaviruses appear to be more resistant than
      other small non-enveloped viruses.

PMID- 23116716
TI  - Timing of caesarean section according to urgency.
AB  - Fetal distress is an emergency condition requiring rapid caesarean delivery.
      Hence, it has been recommended that the decision-to-delivery interval should be
      within 30 mins. Many previous studies have failed to show any improved outcome
      with short decision-to-delivery interval. The reasons are (1) most of these
      studies were of small scale and retrospective with limitation in design; (2) the
      indications for caesarean deliveries recruited in these studies were not specific
      for life-threatening fetal distress; (3) selection bias as clinicians tended to
      deliver worse cases more quickly than less severe cases; (4) correlation was
      analysed between adverse fetal outcome and decision to delivery interval, but
      ignored the bradycardia-to-delivery interval, which reflected the actual duration
      of fetal hypoxia. Latest studies indeed have shown that bradycardia-to-delivery
      interval correlated significantly with arterial pH and base excess in life
      threatening fetal conditions. The longer the bradycardia-to-delivery, the poorer
      the arterial blood gases parameters and neonatal outcomes. This result supports
      that every obstetric unit should have the capability to accomplish emergency
      caesarean section in 30 mins of decision for fetal safety. The Royal College of
      Obstetrics and Gynaecology has standardised the classification of the urgency of
      caesarean delivery, which helps to identify those life-threatening fetal
      conditions that will be benefited from rapid delivery. Training in teamwork and
      communication, availability of anaesthetists, and operation theatre are the main
      factors to achieve a quick caesarean delivery.

PMID- 23116717
TI  - Caesarean section on maternal request for non-medical reasons: putting the UK
      National Institute of Health and Clinical Excellence guidelines in perspective.
AB  - The past decade has seen an unprecedented rise in the demand for caesarean
      sections on maternal request (CSMR), in the absence of any medical or obstetric
      indication. Much of this rise is the result of the perceived myth of safety of
      caesarean sections and the changing attitudes of society and the medical
      profession to childbirth. The debate on the medical, ethical and cost
      implications of rising rates of caesarean section on maternal request have
      prompted the issuing of numerous guidelines over the past few years, including
      one by the National Institute of Health and Clinical Excellence (NICE) in the UK.
      All these guidelines are uniformly less critical of CSMR than guidelines issued
      even a decade ago, and suggest valid management strategies. In this chapter, I
      explore the reasons behind the increase in CSMR and review the current published
      research, including the risks, benefits, controversies, cost and ethics
      surrounding CSMR. I then discuss various guidelines, putting the NICE guidelines
      in perspective.

PMID- 23116718
TI  - Monitoring of perchlorate in diverse foods and its estimated dietary exposure for
      Korea populations.
AB  - The perchlorate concentrations in various Korean food samples were monitored, and
      663 samples belonging to 39 kinds of food were analyzed. The analysis results
      revealed that dairy products contain the highest average concentration of 6.34
      MUg/kg and high detection frequency of over 85%. Fruit and vegetables showed the
      next highest perchlorate concentration with an average of 6.17 MUg/kg.
      Especially, with its average concentration of 39.9 MUg/kg, spinach showed the
      highest perchlorate level among all target food samples studied. Tomato was
      followed by spinach, which showed a high perchlorate average concentration of
      19.8 MUg/kg, and over 7 MUg/kg was detected in ham and sausage (avg. 7.31 MUg/kg)
      and in instant noodles (avg. 7.58 MUg/kg). Less than 2 MUg/kg was detected in
      fishes, meats and beverages. The exposure dose of perchlorate in Korean by food
      intake was calculated on the basis of the analyzed perchlorate levels in this
      study. The daily perchlorate dose to which Korean adults are exposed is 0.04
      MUg/kg bw/day, which is lower than the RfD (0.7 MUg/kg bw/day) value suggested by
      US NAS. This result indicates that Korean people's current exposure to
      perchlorate from domestic food consumption is evaluated as safe.

PMID- 23116719
TI  - Treatment and electricity harvesting from sulfate/sulfide-containing wastewaters
      using microbial fuel cell with enriched sulfate-reducing mixed culture.
AB  - Anaerobic treatment of sulfate-laden wastewaters can produce excess sulfide,
      which is corrosive to pipelines and is toxic to incorporated microorganisms. This
      work started up microbial fuel cell (MFC) using enriched sulfate-reducing mixed
      culture as anodic biofilms and applied the so yielded MFC for treating sulfate or
      sulfide-laden wastewaters. The sulfate-reducing bacteria in anodic biofilm
      effectively reduced sulfate to sulfide, which was then used by neighboring anode
      respiring bacteria (ARB) as electron donor for electricity production. The
      presence of organic carbons enhanced MFC performance since the biofilm ARB were
      mixotrophs that need organic carbon to grow. The present device introduces a
      route for treating sulfate laden wastewaters with electricity harvesting.

PMID- 23116720
TI  - An isotope dilution-precipitation process for removing radioactive cesium from
      wastewater.
AB  - A novel isotope dilution-precipitation method has been developed to remove cesium
      137 from radioactive wastewater. The process involves adding stable cesium
      chloride to wastewater in order to raise the total cesium concentration, which
      then allows both the stable and radioactive cesium ions to be precipitated
      together using sodium tetraphenylborate. This process was investigated utilizing
      laboratory solutions to determine stable cesium dose rates, mixing times, effects
      of pH, and filtration requirements. Once optimized, the process was then tested
      on synthetic wastewater and aqueous low-level waste. Experiments showed the
      reaction to be very quick and stable in the pH range tested, 2.5-11.5. The
      wastewater may need to be filtered using a 0.45-MUm filter, though ferric sulfate
      has been shown to promote coagulation and settling, thereby eliminating the
      necessity for filtration. This investigation showed that this isotope dilution
      precipitation process can remove Cs-37 levels below the U.S. Department of
      Energy's (DOE) Derived Concentration Standard (DCS) of 3.0 * 10(-6) MUCi/mL using
      a single dosage, potentially allowing the wastewater to be discharged directly to
      sanitary sewers.

PMID- 23116721
TI  - Haplotype diversity of 17 Y-STR loci in a Chinese Han population sample from
      Shanxi Province, Northern China.
AB  - The distribution of 17 Y-chromosome STR loci DYS456, DYS389I, DYS390, DYS389II,
      DYS458, DYS19, DYS385a/b, DYS393, DYS391, DYS439, DYS635, DYS392, Y-GATA-H4,
      DYS437, DYS438, and DYS448 haplotypes was determined in a population sample of
      222 unrelated Chinese Han from Shanxi Province, Northern China. A total of 219
      haplotypes were observed, and of these, 216 were unique, while 3 were found two
      times. The overall haplotype diversity was 0.9999 and the discrimination capacity
      was 0.9865, indicating a high potential for differentiating between male
      individuals in this population. Comparison analysis via Analysis of Molecular
      Variance (AMOVA) and construction of MDS plot revealed that Shanxi Han sample
      clusters with Chinese origin populations and stands far apart of the non-Chinese
      populations, justifying the establishment of local databases in Shanxi Han
      population for any future forensic and genetic epidemiology efforts in this
      region.

PMID- 23116722
TI  - Incidental findings in the use of DNA to identify human remains: an ethical
      assessment.
AB  - DNA analysis is increasingly used to identify the remains of victims of conflicts
      and disasters. This is especially true in cases where remains are badly damaged
      and fragmented, or where antemortem records are unavailable. Incidental findings
      (IFs)-that is, genetics-related information for which investigators were not
      looking-may result from these identification efforts employing DNA analysis.
      Because of the critical role played by family members of the missing in
      identification efforts, as well as the familial nature of DNA, identification
      initiatives employing DNA analysis are particularly prone to reveal IFs about
      familial relationships, such as misattributed paternity or false beliefs about
      sibling relationships. Despite forensic scientists' widespread awareness of the
      possibility of generating IFs, to date there has been relatively little explicit
      guidance about their management. This paper fills that gap. It offers substantive
      guidance about the ethical management of IFs in this context. To ensure that the
      analysis addresses actual needs and practices in the field, one author (JDA)
      conducted semi-structured interviews with key informants from six regionally
      diverse organizations involved in post-conflict or post-disaster identification
      efforts. The paper first describes how methods of DNA analysis give rise to IFs.
      Next, it explains the importance of developing an ethically justified general
      policy for managing IFs and discusses features of DNA identification efforts that
      are relevant to such a policy. Then it presents an argument in support of a
      general policy of nondisclosure-specifically, that considerations of fair access
      to the individual and social benefits of identification efforts, and the concern
      to minimize and fairly distribute the risks of participation, support a policy of
      nondisclosure. It concludes by considering some implications of this argument for
      the choice among scientific practices involved in using DNA analysis to identify
      human remains, as well as for managing non-genetic incidental findings.

PMID- 23116723
TI  - A quantitative assessment of a reliable screening technique for the STR analysis
      of telogen hair roots.
AB  - Human telogen hairs are commonly recovered as trace evidence but currently have
      limited use for forensic DNA analysis. Recent studies have revealed that telogen
      roots may be shed with adhering material that may contain cells, thus providing a
      potential source of nuclear DNA. A simple histological stain can be used to
      screen telogen roots for the presence of nuclei, thus increasing the chance of
      selecting roots that may yield nuclear DNA. Using this method to visualise
      nuclei, we surveyed 998 hairs from 136 individuals, quantified the number of
      nuclei, extracted DNA and evaluated corresponding DNA yield and STR profiling
      success. Of the hairs screened, 35% of telogen roots contained nuclei and in
      total 6% of all roots screened had more than 100 nuclei. The number of nuclei
      associated with telogen roots was independent of the presence or absence of
      visibly adhering material, highlighting the importance of using histological
      staining rather than simple microscopic examination. DNA yield and STR profiling
      were significantly and positively correlated with nuclei number. The methods
      presented here can be incorporated into routine trace and DNA analysis providing
      an efficient and cost effective method to screen telogen hairs, and predict STR
      profiling success prior to destructive DNA analysis. The results of this study
      indicate telogen hairs may provide a reliable source of nuclear DNA for use in
      routine casework.

PMID- 23116724
TI  - CT appearance of the pelvis after Cesarean delivery--what is considered normal?
AB  - OBJECTIVE: To describe the normal computed tomography (CT) appearance of the
      pelvis after uncomplicated Cesarean section (C-section). PATIENTS AND METHODS:
      Pelvic CT examinations of 31 patients after uncomplicated C-section were
      reviewed. RESULTS: Higher postoperative day (POD) correlated well with decreases
      in the uterine long axis and endometrial width but did not correlate to scar
      width. Full thickness defect of the uterine wall was revealed in 48% of patients.
      Small volumes of intrauterine gas presented in half of patients at POD 1-26. Free
      pelvic fluid appeared in 74%. Pelvic collections were rare and small. CONCLUSION:
      There is wide variability in pelvic CT appearance following uncomplicated C
      section.

PMID- 23116725
TI  - Rasmussen's aneurysm with aspergilloma in old, healed pulmonary tuberculosis.
AB  - Rasmussen's aneurysm is rare sequelae of pulmonary tuberculosis. The hemoptysis
      caused by rupturing of it is usually massive and needs early and aggressive
      management. To our knowledge, we are the first to report a case of Rasmussen's
      aneurysm with aspergilloma proved pathologically. The accomplishment of
      aspergilloma changes the first choice of treatment from endovascular embolisation
      to surgery.

PMID- 23116726
TI  - Radiology-Pathology Conference: 18F FDG PET-CT imaging of solitary fibrous tumor
      of the pleura.
AB  - Solitary fibrous tumors of the pleura (SFTPs) are mesenchymal neoplasms that
      arise from the pleura. SFTPs can grow slowly and may become big masses with
      malignant behaviors and metastases. The ratio of benign to malignant is 7:1, and
      pathology is necessary to differentiate between benign and malignant. We present
      a case of a 37-year-old man with a presumptive diagnosis of benign SFTP by 18F
      fluorodeoxyglucose positron emission tomography/computed tomography, which was
      confirmed by pathology.

PMID- 23116727
TI  - Impact of 18F-FDG PET/CT on therapeutic decisions in patients with colorectal
      cancer and liver metastases.
AB  - OBJECTIVES: Surgical resection and radio-frequency ablation (RFA) are standard
      therapeutic procedures for colorectal metastases confined to the liver. The
      presence of extrahepatic disease has a significant effect on the management of
      these patients. The goal of this study is to assess the value of positron
      emission tomography/computed tomography with 18F-fluorodeoxyglucose (18F-FDG
      PET/CT) in the decision making whether to perform RFA or surgical resection of
      liver metastases in patients with metastatic colorectal cancer. MATERIAL AND
      METHODS: Thirty-five consecutive patients (23 men, 12 women; age range: 46-78
      years) with colorectal carcinoma and liver metastases were prospectively
      enrolled. Nineteen of them were considered candidates for surgical resection and
      16 for RFA. All underwent 18F-FDG PET/CT, helical computed tomography of the
      chest and abdomen and, some of them, magnetic resonance imaging of the abdomen.
      The 18F-FDG PET/CT studies were performed within 4 weeks from conventional
      imaging, and additional findings were later confirmed or not, either by histology
      or follow up. RESULTS: In the surgical candidate group, 18F-FDG PET/CT detected
      extrahepatic disease, missed by conventional imaging, in 9/19 patients (47.3%).
      These findings directly altered the management in 7 patients (36.8%). In the
      group of RFA candidates, 18F-FDG PET/CT detected additional extrahepatic disease
      in 4/16 patients (25%) and directly altered management in all of them. Overall,
      in 11/35 patients (31.4%), 18F-FDG PET/CT detected extrahepatic metastatic
      disease. CONCLUSION: In patients with colorectal cancer and liver metastases, 18F
      FDG PET/CT provides relevant additional information that has significant impact
      on management.

PMID- 23116729
TI  - Imaging features of breast malignancy: breast ultrasound and MR imaging
      correlation.
AB  - Recent advances in breast imaging, including volumetric breast ultrasound and
      breast magnetic resonance (MR) imaging, now provide multiplanar capability for
      detailed morphologic assessment of breast malignancies. This article describes
      the imaging findings of common breast cancers, utilizing volumetric breast
      ultrasound with MR imaging correlation. Knowledge of the characteristic
      appearances of breast malignancy can facilitate the diagnosis and management of
      breast masses, particularly when obscured by excessive breast density on
      mammography examinations.

PMID- 23116728
TI  - Improved breast cancer detection in asymptomatic women using 3D-automated breast
      ultrasound in mammographically dense breasts.
AB  - Automated breast ultrasound (ABUS)was performed in 3418 asymptomatic women with
      mammographically dense breasts. The addition of ABUS to mammography in women with
      greater than 50% breast density resulted in the detection of 12.3 per 1,000
      breast cancers, compared to 4.6 per 1,000 by mammography alone. The mean tumor
      size was 14.3 mm and overall attributable risk of breast cancer was 19.92 (95%
      confidence level, 16.75 - 23.61) in our screened population. These preliminary
      results may justify the cost-benefit of implementing the judicious us of ABUS in
      conjunction with mammography in the dense breast screening population.

PMID- 23116730
TI  - Periductal mastitis mimicking breast cancer in a male breast.
AB  - Periductal mastitis in a male patient rarely has been reported in the English
      literature. Herein, we now present a rare case of periductal mastitis mimicking
      breast cancer, both clinically and radiologically, in a 37-year-old man.
      Mammogram and sonogram showed a mass with irregular shape, spiculated margin and
      a nipple retraction, mimicking a male breast cancer. Radiologic and pathologic
      correlation is provided.

PMID- 23116731
TI  - Hydatid cyst: an unusual solid breast mass.
AB  - Breast involvement of the hydatid cyst is very rare, and it accounts for 0.27% of
      all cases. Cases reported in the literature are generally about various cystic
      and calcified forms, but the solid form of hydatid cyst in the breast is quite
      rare. It is difficult to differentiate the breast's malignant and benign lesions
      from this form of hydatid cyst by imaging methods. Therefore, we aimed to present
      the mammographical and sonographic findings of a 50-year-old woman patient
      consulted to our mammography unit of whom we determined a Breast Imaging
      Reporting and Data System class 4 solid lesion in the right breast and come out
      as hydatid cyst pathologically.

PMID- 23116732
TI  - In vivo synergistic cytogenetic effects of aminophylline on lymphocyte cultures
      from patients with lung cancer undergoing chemotherapy.
AB  - BACKGROUND: The anti-cancer and cytogenetic effects of aminophylline (AM) have
      been demonstrated in several clinical trials. The aim of the present study was to
      investigate the in vivo cytogenetic effects of AM in newly diagnosed patients
      with small cell (SCLC) and non-small cell lung cancer (NSCLC), receiving
      chemotherapy for the first time. METHODS: Sister chromatid exchanges (SCEs) and
      proliferation rate index (PRI) were evaluated in peripheral blood lymphocyte
      cultures from six patients with SCLC and six patients with NSCLC after the in
      vitro addition of AM and after the in vivo administration of AM in patients
      receiving chemotherapy. RESULTS: The in vitro addition of AM significantly
      increased SCEs only in SCLC patients (p<0.001). The in vivo administration of AM
      after chemotherapy increased SCEs in both cancer types (SCLC: p<0.001, NSCLC:
      p=0.003) and this increase was synergistic, the rates of SCEs in the presence of
      AM were higher than the expected SCE values if the increases above background for
      chemotherapy and AM were independent and additive (SCLC: p<0.001, NSCLC:
      p=0.008). Although in both groups of patients cell division delays were observed
      after the combined chemotherapy plus in vivo AM treatment, the correlation
      between the magnitude of the SCE response and the PRI depression was not
      statistically significant (p>0.05). CONCLUSIONS: These observations suggest that
      AM enhances the results of concurrently administered chemotherapy by
      synergistically increasing its cytogenetic effects in patients with lung cancer.

PMID- 23116733
TI  - The aging immune system: challenges for the 21st century.

PMID- 23116735
TI  - Models for increasing the health workforce.
AB  - A stable human resource base in the health sector is critical to achieving health
      related Millennium Development Goals. There is a severe quantitative and
      qualitative shortfall of healthcare professionals in South Africa, and the
      existing and future health workforce production is inadequate for our healthcare
      needs. The production model must include all healthcare disciplines because the
      quadruple burden of disease necessitates multi-professional healthcare teams
      working synergistically to improve health outcomes and life expectancy.

PMID- 23116734
TI  - Recommendations to improve the National Development Plan for Health.
AB  - In November 2011, a draft National Development Plan (NDP) was released that
      addresses two of South Africa's major challenges: poverty and inequity. Health
      and economic development are interdependent, presenting an important opportunity
      through the NDP to integrate health within goals of broader socio-economic
      development. Reviewing the NDP identified gaps based on evidence and the
      epidemiological risk profile of South Africa. Recommendations to improve the NDP
      and to deal with poverty and inequity should focus on prevention and addressing
      the social determinants of health, including: (i) a multisectoral approach to
      establish a comprehensive early childhood development programme; (ii) fiscal and
      legislative policies to bolster efforts to reduce the burden of non-communicable
      diseases; (iii) promoting and maintaining a healthy workforce; (iv) and promoting
      a culture of evidence-based priority setting. Achieving the goal of 'a long and
      healthy life for all South Africans' will require healthy public policies, well
      functioning institutional and physical infrastructure, social solidarity, and an
      active and conscientious civil society.

PMID- 23116736
TI  - Will clinical associates be effective for South Africa?
AB  - South Africa has developed an innovative mid-level medical worker model that can
      contribute substantively to the development of quality district level health
      care. These clinical associates entered the South African job market in 2011 and
      have reportedly been received favourably. The first cohorts performed well on
      local and national examinations, with pass rates >95%. They have demonstrated
      confidence and competence in the common procedures and conditions encountered in
      district hospitals; reportedly fitted in well at most of the sites where they
      commenced working; and made a significant contribution to the health team work,
      resulting in a demand for more such health workers. Universities and provinces
      involved in producing clinical associates are enthusiastic and committed.
      However, priorities are to: establish sustainable funding sources for training
      and deployment, provide adequate supervision and support, monitor the initial
      impact of the new cadre on health services, and manage the sensitivities of the
      medical and nursing professions around scopes of practice and post levels. Longer
      term concerns are national leadership and support, scaling up of training, the
      development of career pathways, and the improvement of working conditions at
      district hospitals.

PMID- 23116737
TI  - Emergency medicine in South Africa - time to catch up.

PMID- 23116738
TI  - Improving access and quality of care in a TB control programme.
AB  - OBJECTIVES: To use a quality improvement approach to improve access to and
      quality of tuberculosis (TB) diagnosis and care in Cape Town. METHODS: Five
      HIV/AIDS/sexually transmitted infections/TB (HAST) evaluations were conducted
      from 2008 to 2010, with interviews with 99 facility managers and a folder review
      of over 850 client records per evaluation cycle. The data were used in a local
      quality improvement process: sub-district workshops identified key weaknesses and
      facility managers drew up action plans. Lessons learnt and successful strategies
      were shared at quarterly district-wide HIV/TB meetings. RESULTS: Geographical
      access was good, but there were delays in treatment commencement times. Access
      for high-risk clients improved significantly with intensified TB case finding
      made routine in both the HIV counselling and testing and antiretroviral treatment
      (ART) services (p<0.01 for both). Access for children in contact with an
      infectious case has improved but is still low (42% investigated and treated).
      Quality of care was mostly high at baseline (adherence to treatment protocols
      95%). Measurement of body mass index improved from 20% to 62%. The assessment of
      contraception improved from 27% to 58%. Care for co-infected clients showed
      improved use of customised HIV stationery and increased assessment for ART
      eligibility. CONCLUSIONS: The HAST audit contributed to the improved TB cure
      rates by supplementing routine information and involving sub-district managers,
      facility managers and facility staff in a quality improvement process that
      identified local opportunities for programme strengthening.

PMID- 23116739
TI  - High prevalence of diabetes mellitus and metabolic syndrome in a South African
      coloured population: baseline data of a study in Bellville, Cape Town.
AB  - OBJECTIVE: The coloured population has the second-highest prevalence of diabetes
      in South Africa. However, the data were based on a study conducted almost 20
      years ago in a peri-urban coloured population of the Western Cape. We aimed to
      determine the prevalence of diabetes mellitus and metabolic syndrome in an urban
      coloured population in South Africa. DESIGN: In a cross-sectional survey, 642
      participants aged >=31 years were drawn from an urban community of Bellville
      South, Cape Town, from mid-January 2008 to March 2009. Type 2 diabetes was
      assessed according to the WHO criteria, and metabolic syndrome was based on the
      International Diabetes Federation (IDF), ATP III and 2009 Joint Interim Statement
      (JIS) definition. RESULTS: The crude prevalence of 28.2% (age-adjusted 26.3%, 95%
      confidence interval (CI) 22.0 - 30.3) for type 2 diabetes was: 4.4% (age-adjusted
      3.2%, 95% CI 1.6 - 4.9) for impaired fasting glycaemia, and 15.3% (age-adjusted
      15.0%, 95% CI 11.4 - 18.6) for impaired glucose tolerance. Undiagnosed type 2
      diabetes was present in 18.1% (age-adjusted 16.8%, 95% CI 13.3 - 20.4). The crude
      prevalence of metabolic syndrome was higher with the JIS definition (62.0%) than
      the IDF (60.6%), and the National Cholesterol Education Program (NCEP) ATP III
      (55.4%). There was good overall agreement between the MetS criteria, k=0.89 (95%
      CI 0.85 - 0.92). CONCLUSION: The prevalence of diabetes has increased hugely in
      the coloured community, and the high prevalence of undiagnosed diabetes portends
      that cardiovascular diseases might grow to epidemic proportions in the near
      future in South Africa.

PMID- 23116740
TI  - Demographics and management of dog bite victims at a level two hospital in
      KwaZulu-Natal.
AB  - INTRODUCTION: Dog bites are a significant cause of morbidity and mortality
      worldwide, particularly where rabies is endemic. There is also a significant
      financial burden attached to prophylactic treatment to diminish the risk of
      rabies infection. KwaZulu-Natal (KZN) has a high incidence of human rabies yet
      little is known about the demographics of dog bites in the province. OBJECTIVES:
      To analyse the demographics of dog bites in Northern KZN. METHODS: Records of all
      dog bites presenting to the main referral hospital in Northern KZN between August
      2007 and September 2011 were analysed. RESULTS: We collected data for 821
      instances of dog bite. Male children aged 6 - 10 years are most likely to present
      with dog bites, while women >40 years are more likely to present than men in the
      same age bracket. Whilst initial vaccine administration is high (98%) with all
      grades of bite, only 82% of grade 3 bites receive immunoglobulin. CONCLUSION: Our
      results correlate well with two large studies of the demographics of dog bites,
      but are the first to show a reverse in male preponderance of presentations above
      the age of 40 years. Reasons for low rates of immunoglobulin administration in
      grade 3 bites are discussed. Finally, methods are suggested to improve data
      collection and the care of patients presenting with dog bites.

PMID- 23116741
TI  - Factors influencing the development of early- or late-onset Parkinson's disease
      in a cohort of South African patients.
AB  - BACKGROUND: Neurodegenerative disorders such as Parkinson's disease (PD)
      contribute significantly to global disease burden. PD can be categorised into
      early-onset PD (EOPD) with an age at onset (AAO) of <=50 years and late-onset PD
      (LOPD) with an AAO of 50 years. AIMS: To identify factors influencing EOPD and
      LOPD development in a group of patients in South Africa (SA). METHODS: A total of
      397 unrelated PD patients were recruited from the Movement Disorders Clinic at
      Tygerberg Hospital and via the Parkinson's Association of SA. Patient demographic
      and environmental data were recorded and associations with PD onset (EOPD v.
      LOPD) were analysed with a Pearson's Chi-squared test. The English- and Afrikaans
      speaking (Afrikaner) white patients were analysed separately. RESULTS: Logistic
      regression analysis showed that ethnicity (p<0.001) and family history (p=0.004)
      were independently associated with AAO of PD. Average AAO was younger in black,
      coloured and Afrikaner patients than English-speaking white patients. A positive
      family history of PD, seen in 31.1% of LOPD patients, was associated with a
      younger AAO in the study population. CONCLUSIONS: These associations may be
      attributed to specific genetic and/or environmental risk factors that increase PD
      susceptibility and influence the clinical course of the disorder. More studies on
      PD in the unique SA populations are required to provide novel insights into
      mechanisms underlying this debilitating condition.

PMID- 23116742
TI  - Risk factors for substance use in pregnant women in South Africa.
AB  - OBJECTIVES: To study the prevalence of alcohol and substance use in a South
      African antenatal population and its correlates with socio-demographic factors,
      depression and perceived stress. METHODS: A prospective self-report study on all
      women presenting for their first antenatal visit who consented to the study at a
      midwife obstetric unit (MOU) in the East Metropole district, Cape Town, using the
      Alcohol Use Disorders Identification Test (AUDIT), Drug Use Disorders
      Identification Test (DUDIT), Edinburgh Depression Scale (EDS) and Perceived
      Stress Scale (PSS). Statistical analyses using the chi-square test, separate one
      way analyses of variance (ANOVA) and logistic regression analyses were performed
      as appropriate. Outcome measures were depression, alcohol use and substance use.
      RESULTS: The questionnaire was completed by 323 women. During pregnancy 36.8% of
      women smoked, 20.2% used alcohol and 4% used substances. Using EDS cut-off scores
      of 12 and 15, respectively, 48.9% and 33.6% of the sample had scores consistent
      with major depression. An EDS cut-off score of 12 was significantly associated
      with both alcohol use (25.9% v. 15.2%, p=0.019) and risky drinking (76.9% v.
      36.8%, p=0.04), while an EDS cut-off score of 15 was significantly associated
      with substance use (8.2% v. 1.4%, p=0.004) as well as alcohol dependence (23.1%
      v. 3.1%). CONCLUSIONS: We found high rates of both alcohol abuse and antenatal
      depression, and a significant association between depression, substance use and
      alcohol abuse; EDS scores greater than 12 could be used to identify women at risk
      of alcohol dependence and/or substance abuse.

PMID- 23116744
TI  - Impact factors in biliary atresia.

PMID- 23116743
TI  - Safety of nevirapine in HIV-infected pregnant women initiating antiretroviral
      therapy at higher CD4 counts: a systematic review and meta-analysis.
AB  - BACKGROUND: The package insert for nevirapine (NVP) cautions use in HIV-infected
      women (including pregnant women) with CD4 counts >=250 cells/ul. However, recent
      studies showed that the CD4 count of pregnant women receiving antiretroviral
      therapy (ART) was not predictive of NVP toxicity. OBJECTIVES: To determine
      whether ART-naive pregnant women initiating NVP-based ART at higher CD4 counts
      experience greater toxicity compared with pregnant women at lower CD4 counts.
      METHODS: We reviewed studies comparing serious adverse NVP-related events among
      ART-naive pregnant women who commenced therapy at higher v. lower CD4 counts.
      Relevant studies were extracted from PubMed, SCOPUS and EMBASE, major journals
      and conference proceedings prior to December 2011. Authors were contacted for
      additional data. Data were independently extracted and entered into Review
      Manager. RESULTS: Fourteen studies (2 663 participants) were included for
      analysis. The odds ratio (OR) for overall NVP toxicity among pregnant women with
      CD4 <250 cells/ul was 0.61 (95% confidence interval (CI) 0.43 - 0.85). When
      analysis was restricted to prospective studies only (7 studies, 1 318
      participants), the results were consistent for overall NVP toxicity (OR 0.43; 95%
      CI 0.25 - 0.73) and severe hepatotoxicity (OR 0.45; 95% CI 0.22 - 0.90), but not
      for severe cutaneous reaction (OR 0.53; 95% CI 0.26 - 1.10). CONCLUSION:
      Initiating NVP-based ART during pregnancy at CD4 >=250 cells/ul increases
      toxicity risk and should be avoided, necessitating urgent revision of current
      guidelines supporting this practice.

PMID- 23116745
TI  - Maximizing Kasai portoenterostomy in the treatment of biliary atresia: medical
      and surgical options.
AB  - Biliary atresia (BA) remains one of the most challenging conditions in paediatric
      surgery. It has several possible causes, resulting in a range of different
      clinical scenarios. The current therapeutic approach is almost entirely surgical
      with an initial attempt to restore bile flow and preserve the native liver using
      a Kasai-type portoenterostomy. Liver transplantation (cadaveric or living donor)
      is usually reserved for failure or for infants presenting late with end-stage
      cirrhosis. The role of adjuvant medical therapy is unclear and evidence of
      benefit is lacking. Nonetheless, the use of post-operative steroids, prophylactic
      antibiotics and choleretic agents such as ursodeoxycholic acid is common.
      Ideally, the entire pathway should be complementary and seamless with few infants
      dying of end-stage liver disease or uncorrectable associated congenital
      malformations. Experience from high-volume centres suggests that clearance of
      jaundice can be achieved in 50 - 60% of infants with 10-year native liver and
      real survival rates of 45% and 90%, respectively.

PMID- 23116746
TI  - Medical management of the 'failing' Kasai portoenterostomy.
AB  - The only effective treatment for 'failing' Kasai portoenterostomy is liver
      transplantation (LT). However, to maximise a patient's chances to achieve the
      proclaimed >95% survival with sequential surgical management, medical follow-up
      and treatment must be planned carefully. This includes routine fat-soluble
      vitamin supplementation with choleretics, aggressive nutritional support, regular
      ultrasonography, optimal general paediatric care, and psychological support for
      the family once complications arise. Careful timing of LT is of critical
      importance, although recent trends include earlier consideration of LT in
      children with biliary atresia. This management can only be offered through
      centralised, specialised national services. Due to its ramifications in
      paediatric surgery, dietetics, metabolic, social, adolescent and transplantation
      medicine, paediatric hepatology is a fine example of patient care that is
      genuinely multidisciplinary.

PMID- 23116747
TI  - Solving difficult hepatobiliary problems in children.
AB  - Most difficult hepatobiliary (HPB) problems in infancy and childhood result from
      pathological anatomical/mechanical derangements; therefore, surgery on the liver
      and bile ducts depends on a detailed understanding of liver structure, function
      and repair response to injury or disease. The surgeon must be aware of the very
      diverse range of anatomical variations. Perhaps key to improving the outcome of
      paediatric HPB surgery is centralised management and associating this with a
      paediatric liver transplant programme, which adds expertise and, frequently, the
      added benefit of adult HPB surgical input to paediatric surgical care. In the
      United Kingdom, this has resulted in excellent measurable benefit, particularly
      in the management of biliary atresia, but also of choledochal cysts, portal
      hypertension and liver tumours. These conditions are briefly discussed here, with
      focus on the technical aspects of operative management.

PMID- 23116748
TI  - Selection and work-up for liver transplantation.
AB  - The evaluation of the liver transplantation candidate is intended to confirm the
      indication for transplantation, determine the severity of disease, exclude contra
      indications, optimise pre-transplantation care and candidate condition, and
      educate the patient and family on post-procedure expectations. This article is
      intended as a guide for the appropriate selection and work-up of patients for
      liver transplantation.

PMID- 23116749
TI  - Paediatric living donor liver transplantation.
AB  - Paediatric liver transplantation is a highly effective therapy for children with
      end-stage liver disease; 1-year survival rates currently exceed 90% and long-term
      survivors enjoy an almost-normal quality of life. Key to the success of
      paediatric liver transplantation has been the technical refinement to provide
      children with suitably sized grafts. Adult-to-paediatric living donor liver
      transplantation highlights this success and has been instrumental in decreasing
      waiting list mortality to less than 5%.

PMID- 23116750
TI  - A review of paediatric liver resections in Johannesburg: experiences and
      preferred technique.
AB  - BACKGROUND: Liver resections are widely performed in paediatric surgery. Many
      techniques exist to achieve vascular control, minimise bleeding and complete the
      parenchymal division. METHODS: We retrospectively reviewed all liver resections
      performed in the Department of Paediatric Surgery at our institution between
      January 2005 and June 2012. Data pertaining to basic demographics, indications
      for surgery, parenchymal transection techniques, morbidity, mortality and
      histology were collated. RESULTS: Twenty-one resections were performed in
      children aged 6 weeks - 11 years; 18 for malignant liver disease (including 9
      hepatoblastomas), and 3 for benign disease. We describe 1 peri-operative
      mortality secondary to torsion of the liver remnant, and no surgical morbidity.
      Three cases underwent total hepatic vascular exclusion with sharp parenchymal
      transection. The remaining patients underwent selective vascular inflow and
      outflow control using the Cavitron Ultra Sonic Aspirator and Harmonic Scalpel to
      divide the parenchyma. CONCLUSION: Care for these patients should be
      multidisciplinary. High-volume units and access to liver transplantation offer
      optimal results. No technique is proven superior to the 'clamp crush' technique
      of parenchymal transection. Knowledge of hepatic anatomy is key to minimising
      morbidity, and surgeons should be familiar with and have the flexibility to use
      all techniques of vascular control.

PMID- 23116751
TI  - Endoscopic injection sclerotherapy for bleeding varices in children with
      intrahepatic and extrahepatic portal venous obstruction: benefit of injection
      tract embolisation.
AB  - BACKGROUND: The outcome of sclerotherapy for bleeding oesophageal varices may be
      influenced by injection technique. In a previous study at our institution,
      sclerotherapy was associated with a high re-bleeding rate and oesophageal
      ulceration. Embolisation of the injection tract was introduced in an attempt to
      reduce injection-related complications. METHODS: To determine the outcome and
      effectiveness of injection tract embolisation in reducing injection-related
      complications, we retrospectively reviewed a series of 59 children who underwent
      injection sclerotherapy for oesophageal varices (29 for extrahepatic portal vein
      obstruction (EHPVO) and 30 for intrahepatic disease) in our centre. RESULTS:
      Sclerotherapy resulted in variceal eradication in only 11.8% of the children
      (mean follow-up duration: 38.4 months). Variceal eradication with sclerotherapy
      alone was achieved in 20.7% and 3.3% of EHPVO and intrahepatic disease patients,
      respectively. Injection tract embolisation was successful in reducing the number
      of complications and re-bleeding rates. Complications that arose included:
      transient pyrexia (16.7%); deep oesophageal ulcers (6.7%); stricture formation
      (3.3%); and re-bleeding before variceal sclerosis (23%). CONCLUSION: Injection
      sclerotherapy did not eradicate oesophageal varices in most children. Injection
      tract embolisation by sclerosant was associated with fewer complications and
      reduced re-bleeding rates.

PMID- 23116752
TI  - Lessons from the hepatoblastoma-familial polyposis connection.
AB  - BACKGROUND: Approximately one-third of hepatoblastoma (HB) patients have
      associated congenital abnormalities, but familial recurrence is rare, except in
      association with familial adenomatous polyposis (FAP). This correlation may be
      missed if not actively sought, with implications for long-term outcome and
      management. METHODS: We retrospectively investigated 3 families with an HB
      familial polyposis connection, from a cohort of 113 FAP families (1989 - 2010).
      Data were analysed to assess clinical problem, treatment, complications and
      management. Long-term morbidity and functional outcome were analysed to identify
      management difficulties. RESULTS: Three FAP families (2.65%) had an HB
      association. In one case, undiagnosed FAP at the time of HB diagnosis was only
      detected 5 years later, when the mother presented with advanced colorectal
      carcinoma. A chromosome 5 APC gene mutation (exon 15 codon 793 C->T) was then
      identified. In a second case, a non-related male child presented with a stage 4
      multifocal HB with lung metastases. Genetic studies identified an APC gene
      mutation (exon 6 codon 232 C->T). Further family investigation showed >20 related
      FAP patients. A third HB-FAP association was identified in a known FAP family
      early in the study, prior to the availability of genetic testing. CONCLUSION:
      Although a rare association, a family history of FAP in HB patients is an
      important 'hidden connection'. Germline variation may be outside the usual FAP
      gene site. Identifying families with unknown HB/FAP is important due to long-term
      management implications and follow-up.

PMID- 23116753
TI  - Problems related to CMV infection and biliary atresia.
AB  - BACKGROUND: Human cytomegalovirus (CMV) infection is related to biliary disease,
      being cholestatic in its own right. It has also been associated with intrahepatic
      bile duct destruction and duct paucity, indicating a possible role in
      extrahepatic biliary atresia pathogenesis and progression. When related to
      biliary atresia CMV IGM positive patients appear to have more liver damage thus
      affecting outcome. Methods We carried out a retrospective chart review on 74
      patients diagnosed with hepatobiliary disease (2000-2011). METHODS: included
      clinical and outcome review as well as evaluation of potential risk factors.
      Patients were divided into 2 groups those with biliary atresia and those without
      Biliary atresia (BA). The 2 groups were compared in terms of CMV infection.
      RESULTS: Of the 74 patients with hepatobiliary disease investigated, 39 (52%)
      were shown to have Biliary atresia and 35 other cases. 12 of the BA group and 4
      of the non-BA were excluded due to lack of data Twenty-seven (69%) of the biliary
      atresia group had sufficient available data for review. Of these, 21 (78% of the
      27) had CMV positivity (IgM/IgG) on testing, with 20 of these being IgM positive
      versus 8 in the non-biliary atresia group. (p<0.01) Two (7.5%) of 27 BA infants
      were HIV exposed being born to HIV positive mothers whereas HIV positivity was
      observed in 7 (35%) of the non-biliary atresia group (p<0.01). Both of these
      biliary atresia infants were CMV IgM positive. Long- term outcome of the 21 with
      CMV positivity showed 3 deaths (non-HIV exposed) and a higher rate of severe
      early liver damage suggesting a poorer outcome in CMV affected patients.
      CONCLUSIONS: This study suggests a correlation between CMV exposure, infection
      and surgical hepatobiliary disease including biliary atresia affecting
      outcome.HIV positivity does not preclude Biliary atresia and should be further
      investigated.

PMID- 23116754
TI  - Dynamic expression characteristics of Notch signal in bone marrow-derived
      mesenchymal stem cells during the process of differentiation into hepatocytes.
AB  - Notch signaling is often involved in early development which helps to determine
      the differentiation state and fate of stem cells destined to form different
      tissues in the body. Its role in the differentiation of BM-MSCs (bone marrow
      derived mesenchymal stem cells) is much less clear. As there is great interest in
      the potential of BM-MSCs as a source of cells for treating liver damage, it is
      important to understand if Notch signaling promotes or suppresses BM-MSCs
      differentiation into hepatocytes. In the present study, RT-PCR, Western blot
      results and morphologic changes demonstrated that BM-MSCs could successfully
      differentiate into hepatocytes in our special induction system including the
      tissue extract of damaged liver. On the 21st day when the differentiation
      direction was determined in BM-MSCs, the mRNA level of Jagged2, Delta1, Delta3,
      Notch1, Notch2, Notch3 and Presenilin1, was significantly lower than that on days
      0, 7, and 11. In the further experiments, down-regulation of Notch signaling was
      shown to be critical for BM-MSCs to differentiate into hepatocytes, as increased
      Jagged1 resulted in up-regulated Notch activation leading to higher levels of
      expression of Hes1 and Hey1, which completely blocked Albumin expresion in BM
      MSCs. These results in our study showed that Notch signaling in BM-MSCs was
      necessary to initiate differentiation into hepatocytes, but must be down
      regulated for the differentiation to proceed continuously.

PMID- 23116755
TI  - External gill motility and striated muscle presence in the embryos of anuran
      amphibians.
AB  - Anuran external gills were assessed for motility and striated muscle content in
      16 species from seven families. Motility of three kinds was observed. Pulsatory
      movements related to heart beat rhythm were common. In embryos developing to a
      late stage before hatching, movements of the whole embryo were frequent, with
      gills rearranging as a consequence. The only clearly active movement, presumably
      muscle driven, was 'gill flicking', a posterior movement of the entire gill into
      the body either on one side only, or both together, followed by a return to the
      normal spread-out position. Some species may actively spread their gills when
      hanging from the water surface film, but we did not observe this. In some
      species, active gill movement developed over time, but we were not able to follow
      all species over such a developmental sequence. The relationship between active
      motility and muscle content was good in most cases. Observations on late stage
      embryos of the aromobatid Mannophryne trinitatis are presented for the first
      time. In one species, we noted spread external gills being used to adhere
      hatchlings to a surface.

PMID- 23116756
TI  - IL-23 is pro-proliferative, epigenetically regulated and modulated by
      chemotherapy in non-small cell lung cancer.
AB  - BACKGROUND: IL-23 is a member of the IL-6 super-family and plays key roles in
      cancer. Very little is currently known about the role of IL-23 in non-small cell
      lung cancer (NSCLC). METHODS: RT-PCR and chromatin immunopreciptiation (ChIP)
      were used to examine the levels, epigenetic regulation and effects of various
      drugs (DNA methyltransferase inhibitors, Histone Deacetylase inhibitors and
      Gemcitabine) on IL-23 expression in NSCLC cells and macrophages. The effects of
      recombinant IL-23 protein on cellular proliferation were examined by MTT assay.
      Statistical analysis consisted of Student's t-test or one way analysis of
      variance (ANOVA) where groups in the experiment were three or more. RESULTS: In a
      cohort of primary non-small cell lung cancer (NSCLC) tumours, IL-23A expression
      was significantly elevated in patient tumour samples (p < 0.05). IL-23A
      expression is epigenetically regulated through histone post-translational
      modifications and DNA CpG methylation. Gemcitabine, a chemotherapy drug indicated
      for first-line treatment of NSCLC also induced IL-23A expression. Recombinant IL
      23 significantly increased cellular proliferation in NSCLC cell lines.
      CONCLUSIONS: These results may therefore have important implications for treating
      NSCLC patients with either epigenetic targeted therapies or Gemcitabine.

PMID- 23116758
TI  - Free vaccine programs to cocoon high-risk infants and children against influenza
      and pertussis.
AB  - An adult immunization strategy called "cocooning" is a relatively new concept,
      referring to immunizing close contacts of infants and high-risk children, thereby
      limiting pathogen exposure. This report explores the adoption of free vaccine
      programs in US children's hospitals and shares our own institutions' experiences
      in implementing free vaccine programs for close contacts of our patients.

PMID- 23116759
TI  - Hand hygiene compliance by visitors to hospitals--can we do better?

PMID- 23116761
TI  - Screening for MRSA: reply to Kutlu et al and Gomes et al.

PMID- 23116762
TI  - Institutional MRSA screening practice and policies.

PMID- 23116763
TI  - Control of adipogenesis by ezrin, radixin and moesin-dependent biomechanics
      remodeling.
AB  - We have recently shown that altered stem cell biomechanics can regulate the
      lineage commitment through a family of the membrane-cytoskeleton linker proteins
      (ERM; ezrin, radixin, moesin). The ERM proteins not only modulate the cell
      stiffness and actin cytoskeleton organization, but also rearrange focal adhesions
      and therefore influence the biochemically-directed stem cell differentiation.
      Combining silencing RNA, atomic force microscopy, and fluorescence microscopy,
      the role of the ERM proteins involved in the regulation of stem cell biomechanics
      and adipogenic differentiation was quantitatively determined. Transient ERM
      knockdown by RNAi caused disassembly of actin stress fibers and focal adhesions
      and a decrease in the cell stiffness. The silencing RNA treatment not only
      induced mechanical changes in stem cells but impaired adipogenesis in a time
      dependent manner. While siRNA ERM treatment at day 0 substantially interfered
      with adipogenesis, the same treatment at day 3 of adipogenic differentiation
      significantly facilitated adipogenesis, as assessed by the expression of
      adipocyte-specific markers. The intact biomechanics homeostasis appears to be
      critical for the adipogenic induction. These findings may lead to potential
      biomechanical intervention techniques and methodologies to control the fate and
      extent of adipogenesis that would likely be involved in stem cell-based
      therapeutics for soft tissue repair and regeneration.

PMID- 23116764
TI  - A hip joint kinematics driven model for the generation of realistic thigh soft
      tissue artefacts.
AB  - In human movement analysis, accuracy and robustness of the algorithms used to
      determine the location of centres of rotation from stereophotogrametric data
      depend mainly on their capacity to deal with the artefacts due to soft tissue
      deformation (STA). While evaluating these algorithms using a mathematical
      simulation approach, effectual realizations of STAs are needed. This study aimed
      at accomplishing this objective by modelling STAs, in twelve selected areas of
      the thigh, as a linear function of the hip angles, assuming no knee joint
      movement. The proposed model was calibrated and assessed using ex-vivo
      experiments. This entailed that only the component of the STA due to skin
      stretching was accounted for. Photogrammetric data of markers placed on the skin
      and on hip-bone and femur pins were recorded during passive flexion-extension, ab
      adduction, rotation and circumduction of the hip joint. Artefact skin marker
      displacements were represented in a femur embedded anatomical frame. Model
      parameters were estimated by minimizing the least squares difference between
      measured and modelled STAs. The STA affecting a skin marker placed in a given
      thigh location of a given subject could be modelled with a high accuracy (median
      root mean square difference over 4 subjects*3 trials*12 markers*3 coordinates:
      0.8 mm-inter quartile range 1.0 mm). This was also true for a hip joint movement
      different from the one used to calibrate the model. High inter-subject
      variability of the model parameters confirmed the subject-dependency of the
      phenomenon.

PMID- 23116765
TI  - Comment on "injectable calcium phosphate cement for augmentation around
      cancellous bone screws. In vivo biomechanical studies" [Journal of Biomechanics
      vol. 45 (7) (2012) pp. 1156-1160].

PMID- 23116766
TI  - Estimating optimal shoulder immobilization postures following surgical repair of
      massive rotator cuff tears.
AB  - Although shoulder immobilization is commonly prescribed following surgical repair
      of rotator cuff tears there is no consensus about the best shoulder
      immobilization postures. A musculoskeletal model was used with a minimax
      algorithm to estimate optimal post-operative shoulder immobilization postures for
      massive rotator cuff tears involving the supraspinatus and infraspinatus. An
      optimal posture was defined as one in which the stresses in the repaired tendons
      and the angle of humerus elevation were minimized. The optimal post-operative
      shoulder immobilization postures were with the humerus elevated and externally
      rotated. Elevation increased with the severity of the tear from 21 degrees  to 45
      degrees  while external rotation decreased slightly from 23 degrees  to 18
      degrees . The minimax algorithm effectively balanced the competing criteria,
      resulting in feasible postures that did not overstress the repaired tendons. This
      method could be used to guide prescription of shoulder immobilization postures
      for various injuries.

PMID- 23116767
TI  - Intracorporeal versus extracorporeal anastomosis during laparoscopic right
      hemicolectomy - systematic review and meta-analysis.
AB  - BACKGROUND: Since 2005, after an initial scanty spreading, the vast majority of
      surgeons advice against the intracorporeal ileocolic anastomosis following right
      hemicolectomies. In the subsequent years, greater interest was re-discovered for
      the intracorporeal ileocolic anastomosis formed after video-assisted right
      hemicolectomies OBJECTIVE: The aim of this systematic review is to compare the
      intra-abdominal versus extra-abdominal anastomosis after right laparoscopic
      colectomy. DATA SOURCES: A systematic search was conducted in Medline, Embase,
      Cochrane Central Register of Controlled Trials, CINAHL, BioMed Central and the
      Science Citation Index. STUDY SELECTION: A total of 191 publications were
      identified; seven non-randomized studies published between 2004 and 2012 with a
      total of 945 patients, who underwent laparoscopic right colectomy for malignant
      and benign disease, were included in this systematic review. INTERVENTION: Intra
      abdominal versus extra-abdominal confectioning of ileo-coloc anastomosis after
      right laparoscopic colectomy. MAIN OUTCOME MEASURES: Anastomotic leak, overall
      post-operative morbidity and overall 30-days post-operative mortality. RESULTS:
      Anastomotic leak rate resulted similar in IA (1.13%) and EA (1.84%) group
      (P=0.81, OR of 0.90, 95% CI 0.24-3.10) (Chi(2)=3.90, P=0.42, I(2)=0%). The
      mortality rate was lower in the IA group (0.34% versus 1.32%), although no
      statistically difference was demonstrated between the two groups (P = 0.48, OR of
      0.52 95% CI 0.09-3.10). It was not possible to conduct a meta-analysis of post
      operative morbidity as the data reported in the included studies were too
      heterogeneous. LIMITATIONS: The weakness in our results was due to the lack of
      evidence in current published literature. CONCLUSIONS: The present systematic
      review of literature and meta-analysis failed to solve the controversies between
      intracorporeal and extracorporeal anastomosis after laparoscopic right
      hemicolectomy. Future randomized, controlled trials are needed to further
      evaluate different surgical anastomosis after laparoscopic right hemicolectomy.

PMID- 23116768
TI  - Interventional revisions of malfunctions affecting surgically implanted port
      catheters for hepatic artery infusion.
AB  - PURPOSE: Despite high response rates, feasibility of hepatic artery infusion
      (HAI) is impaired by frequent malfunctions of surgically implanted catheters
      (SIC). The aim of this study is to analyze the incidence and the types of
      malfunctions affecting the SIC and the success rate of interventional revisions
      (IR) in restoring patency to these catheters. METHODS: In a single center, 101
      consecutive patients treated with HAI through SIC over 10 years were
      retrospectively reviewed. The studied group (+IR) was composed of patients
      referred to interventional radiology for repair of catheter malfunctions. The
      overall patency of catheters in the +IR group was compared with the overall
      patency of a control group composed of patients without catheter malfunction (no
      IR). RESULTS: 86 patients were included with no difference in baseline
      characteristics between +IR (n = 40) and no IR (n = 46). There were no
      significant differences in overall patency between both groups (8.4 courses vs.
      8.4 courses, p = 0.99). Furthermore, with an overall success rate of 72.5%, IR
      significantly improved the mean primary patency from 2.4 to 8.4 courses (p <
      0.0001) in the +IR group. CONCLUSION: By restoring a normal patency to SIC
      affected by different types of malfunctions, IR improves feasibility of HAI.

PMID- 23116769
TI  - Description of the human hand grasp using graph theory.
AB  - This paper presents a method to describe and analyze the human hand grasp
      postures so as to indicate which fingers should act during grasping and the
      required movements of those fingers. The method first describes the human hand
      with human hand tree graph and incidence matrix, and then the relationship
      between the human hand and the grasped object is described by grasp contact graph
      and basic cycle matrix that can be divided into an identity matrix and a Bf12
      matrix. The nonzero columns of the Bf12 matrix can be described by a graph called
      VF-tree, which can indicate which fingers are active while grasping and the
      required degree of freedom of each finger. The method is validated by describing
      and analyzing the six basic grasp postures of the human hand.

PMID- 23116770
TI  - Expression and assembly of active human cardiac troponin in Escherichia coli.
AB  - Cardiomyopathy-related mutations in human cardiac troponin subunits, including
      troponin C (hcTnC), troponin I (hcTnI), and troponin T (hcTnT), are well
      documented. Recently, it has been recognised that human cardiac troponin (hcTn)
      is a sophisticated allosteric system. Therefore, the effect of drugs on this
      protein complex should be studied with assembled hcTn rather than a short
      fragment of a subunit or the subunit itself. Here, we describe the expression and
      assembly of active hcTn in Escherichia coli, a novel method that is rapid and
      simple, and produces large amounts of functional hcTn.

PMID- 23116772
TI  - Effects of AMPK activation and combined treatment with AMPK activators and
      somatostatin on hormone secretion and cell growth in cultured GH-secreting
      pituitary tumor cells.
AB  - We investigated the effects of the AMPK activator AICAR as compared to
      somatostatin-14 on cell viability and GH secretion in human GH-secreting
      pituitary adenomas in vitro and in rat GH3 cells. Overnight treatment with AICAR
      increased phospho-(threonine-172) AMPK levels (activated AMPK) in cultured human
      adenomas. As to the effects on cell viability, four adenomas out of 15 were
      responsive to AICAR (0.4mM) and five adenomas were responsive to SS-14 (100 nM).
      One adenoma was responsive to both somatostatin and AICAR. The effects of
      cotreatment with SS-14 and AICAR were investigated in eight adenomas. In two
      adenomas, the effects of AICAR+SS-14 did not exceed the effect of AICAR. In two
      adenomas which were not responsive to either AICAR or SS-14, the cotreatment was
      able to reduce cell viability versus control. Two adenomas were not responsive to
      any treatment. As to the effects on GH secretion, nine adenomas out of 15 were
      responsive to AICAR. Twelve adenomas were responsive to SS-14. Eight adenomas
      were responsive to both AICAR and SS-14. Cotreatment exceeded the effect of
      single treatments in 4 out of 10 adenomas. In GH3 cells, AICAR reduced the
      activity of p70S6 kinase, which plays an important role in cell growth. SS-14 did
      not affect significantly AMPK phosphorylation and p70S6K activity but it was able
      to enhance the inhibitory effect of AICAR on phospho-S6 levels. Moreover, AICAR
      and SS-14 reduced ERK phosphorylation with a different time course. The combined
      treatment reduced phospho-ERK levels at any time point.

PMID- 23116771
TI  - Imaging and genetics of language and cognition in pediatric epilepsy.
AB  - This paper presents translational aspects of imaging and genetic studies of
      language and cognition in children with epilepsy of average intelligence. It also
      discusses current unanswered translational questions in each of these research
      areas. A brief review of multimodal imaging and language study findings shows
      that abnormal structure and function, as well as plasticity and reorganization in
      language-related cortical regions, are found both in children with epilepsy with
      normal language skills and in those with linguistic deficits. The review on
      cognition highlights that multiple domains of impaired cognition and
      abnormalities in brain structure and/or connectivity are evident early on in
      childhood epilepsy and might be specific for epilepsy syndrome. The description
      of state-of-the-art genetic analyses that can be used to explain the convergence
      of language impairment and Rolandic epilepsy includes a discussion of the
      methodological difficulties involved in these analyses. Two junior researchers
      describe how their current and planned studies address some of the unanswered
      translational questions regarding cognition and imaging and the genetic analysis
      of speech sound disorder, reading, and centrotemporal spikes in Rolandic
      epilepsy.

PMID- 23116774
TI  - The automated malnutrition assessment.
AB  - OBJECTIVE: We propose an automated nutritional assessment algorithm that provides
      a method for malnutrition risk prediction with high accuracy and reliability.
      METHODS: The database used for this study was a file of 432 patients, where each
      patient was described by 4 laboratory parameters and 11 clinical parameters. A
      malnutrition risk assessment of low (1), moderate (2), or high (3) was assigned
      by a dietitian for each patient. An algorithm for data organization and
      classification using characteristic metrics for each patient was developed. For
      each patient, the algorithm characterized the patients' unique profile and built
      a characteristic metric to identify similar patients who were mapped into a
      classification. For each patient, the algorithm characterized the patients'
      classification. RESULTS: The algorithm assigned a malnutrition risk level for
      different training sizes that were taken from the data. Our method resulted in
      average errors (distance between the automated score and the real score) of
      0.386, 0.3507, 0.3454, 0.34, and 0.2907 for the 10%, 30%, 50%, 70%, and 90%
      training sizes, respectively. Our method outperformed the compared method even
      when our method used a smaller training set than the compared method. In
      addition, we showed that the laboratory parameters themselves were sufficient for
      the automated risk prediction and organized the patients into clusters that
      corresponded to low-, low-moderate-, moderate-, moderate-high-, and high-risk
      areas. The organization and visualization methods provided a tool for the
      exploration and navigation of the data points. CONCLUSION: The problem of rapidly
      identifying risk and severity of malnutrition is crucial for minimizing medical
      and surgical complications. These are not easily performed or adequately
      expedited. We characterized for each patient a unique profile and mapped similar
      patients into a classification. We also found that the laboratory parameters were
      sufficient for the automated risk prediction.

PMID- 23116773
TI  - Testosterone regulation of Akt/mTORC1/FoxO3a signaling in skeletal muscle.
AB  - Low endogenous testosterone production, known as hypogonadism is commonly
      associated with conditions inducing muscle wasting. Akt signaling can control
      skeletal muscle mass through mTOR regulation of protein synthesis and FoxO
      regulation of protein degradation, and this pathway has been previously
      identified as a target of androgen signaling. However, the testosterone
      sensitivity of Akt/mTOR signaling requires further understanding in order to
      grasp the significance of varied testosterone levels seen with wasting disease on
      muscle protein turnover regulation. Therefore, the purpose of this study is to
      determine the effect of androgen availability on muscle Akt/mTORC1/FoxO3a
      regulation in skeletal muscle and cultured C(2)C(12) myotubes. C57BL/6 mice were
      either castrated for 42 days or castrated and treated with the nandrolone
      decanoate (ND) (6 mg/kg bw/wk). Testosterone loss (TL) significantly decreased
      volitional grip strength, body weight, and gastrocnemius (GAS) muscle mass, and
      ND reversed these changes. Related to muscle mass regulation, TL decreased muscle
      IGF-1 mRNA, the rate of myofibrillar protein synthesis, Akt phosphorylation, and
      the phosphorylation of Akt targets, GSK3beta, PRAS40 and FoxO3a. TL induced
      expression of FoxO transcriptional targets, MuRF1, atrogin1 and REDD1. Muscle
      AMPK and raptor phosphorylation, mTOR inhibitors, were not altered by low
      testosterone. ND restored IGF-1 expression and Akt/mTORC1 signaling while
      repressing expression of FoxO transcriptional targets. Testosterone (T)
      sensitivity of Akt/mTORC1 signaling was examined in C(2)C(12) myotubes, and mTOR
      phosphorylation was induced independent of Akt activation at low T
      concentrations, while a higher T concentration was required to activate Akt
      signaling. Interestingly, low concentration T was sufficient to amplify myotube
      mTOR and Akt signaling after 24 h of T withdrawal, demonstrating the potential in
      cultured myotubes for a T initiated positive feedback mechanism to amplify
      Akt/mTOR signaling. In summary, androgen withdrawal decreases muscle myofibrillar
      protein synthesis through Akt/mTORC1 signaling, which is independent of AMPK
      activation, and readily reversible by anabolic steroid administration. Acute Akt
      activation in C(2)C(12) myotubes is sensitive to a high concentration of
      testosterone, and low concentrations of testosterone can activate mTOR signaling
      independent of Akt.

PMID- 23116775
TI  - Evaluation of lipid peroxidation and antioxidant system in healthy iron-replete
      infants receiving iron prophylaxis.
AB  - OBJECTIVE: Iron supplementation is commonly recommended for infants; however,
      there are some reports that it causes oxidative damage. The aim of this study was
      to investigate the potential effects of iron supplementation at 4 mo of age, for
      a period of 2 mo, on lipid peroxidation and free radical scavenging enzymes.
      METHODS: Twenty-seven healthy 4-mo-old infants chosen randomly and given iron
      supplementation (ferrous sulfate, 10 mg of elemental iron per day) constituted
      the study group and 26 healthy 4-mo-old infants who were chosen randomly and not
      given iron supplementation constituted the control group. Weight, height, head
      circumference, complete blood cell count, serum ferritin level and
      intraerythrocytic zinc, iron, copper, malondialdehyde, catalase, superoxide
      dismutase, and glutathione peroxidase levels were measured in the two groups at 4
      and 6 mo of life. RESULTS: Compared with controls at 6 mo of age, no significant
      differences were observed for intraerythrocytic zinc (0.5 +/- 0.1 versus 0.6 +/-
      0.2 MUg/mL, P > 0.05), copper (0.2 +/- 0.1 versus 0.2 +/- 0.2 MUg/mL, P > 0.05),
      iron (130.8 +/- 10.9 versus 127.4 +/- 11.1 MUg/mL, P > 0.05), malondialdehyde
      (21.4 +/- 3.5 versus 22.4 +/- 2.3 nmol/g of hemoglobin, P > 0.05), catalase
      (135.4 +/- 23.9 versus 135.1 +/- 23.3 MU/g of hemoglobin, P > 0.05), superoxide
      dismutase (1736.4 +/- 141.1 versus 1701.3 +/- 103.9 U/g of hemoglobin, P > 0.05),
      and glutathione peroxidase (8.9 +/- 1.6 versus 8.4 +/- 1.6 U/g of hemoglobin, P >
      0.05) levels. CONCLUSION: Our study indicates that the supplemental use of
      elemental iron 10 mg/d for a period of 2 mo in healthy iron-replete infants did
      not cause lipid peroxidation or an impairment of antioxidant status.

PMID- 23116776
TI  - New clinicians require ongoing training to ensure high inter-rater reliability of
      the Subjective Global Assessment.

PMID- 23116777
TI  - Participation of hippocampal agmatine in spatial learning: an in vivo
      microdialysis study.
AB  - Agmatine, decarboxylated arginine, is widely distributed in mammalian brains and
      is considered as a novel putative neurotransmitter. Recent research demonstrates
      spatial learning-induced increases in agmatine in memory-related structures at
      the tissue and presynaptic terminal levels. By using the in vivo microdialysis
      technique coupled with highly sensitive liquid chromatography/mass spectrometry
      assay, we investigated dynamic changes of extracellular agmatine in the rat
      dorsal hippocampus before, during and after water maze training to find a fixed
      hidden platform on the first and forth day of testing. It was firstly noted that
      the basal level of extracellular agmatine was significantly elevated on day 4.
      While swimming per se had no effect, a rapid rise (2-6 folds) in extracellular
      agmatine was observed during water maze training regardless of testing day. Such
      learning-induced rise was found to successively lessen across the multiple blocks
      of training on day 1. However, this pattern was reversed on day 4 when the
      platform was removed during the final training trial. The present study, for the
      first time, demonstrates water maze training-induced increase of extracellular
      agmatine in the dorsal hippocampus. The results suggest a role of endogenous
      agmatine in the encoding and retrieval of spatial information.

PMID- 23116778
TI  - Effect of quorum quenching on the reactor performance, biofouling and biomass
      characteristics in membrane bioreactors.
AB  - Enzymatic quorum quenching has recently been shown to be a promising approach to
      mitigate biofouling in membrane filtration processes. However, its universal
      effectiveness and mechanisms need further research. In this study, acylase was
      immobilized into sodium alginate capsules for enzymatic quorum quenching in MBRs
      operated at typical sludge concentrations (MLSS ~ 10 g/L) for extended period of
      time. The results showed that quorum quenching influenced sludge characteristics
      and biofouling, while not impacting pollutant degradation. Better sludge
      settleability, smaller sludge particle size, less SMP and EPS production, lower
      apparent viscosity and higher zeta potential of mixed liquor were observed with
      quorum quenching. Quorum quenching also influenced the characteristics, behavior
      and function of SMP and EPS, which weakened biofilm formation ability but
      enhanced membrane filterability.

PMID- 23116779
TI  - A qualitative study of tobacco dependence treatment in 19 US dental hygiene
      programs.
AB  - INTRODUCTION: The US Public Health Service calls for health professionals to
      provide tobacco dependence counseling for patients. The purpose of this study was
      to understand how dental hygiene programs make decisions about and provide
      training for tobacco dependence counseling to help them graduate more fully
      competent hygienists. METHODS: We conducted interviews (N = 32) with mainly
      program and clinic directors from 19 US dental hygiene education programs for
      this qualitative case study. We explored fluoride therapy training and tooth
      whitening training for comparison. Two analysts summarized the transcripts into a
      case study for each program. RESULTS: All programs reported a similar process of
      learning about and choosing a method for teaching the topics explored. The
      programs used a common process, ADPIE (assess, diagnose, plan, implement,
      evaluate), to structure students'clinical encounters. Almost all programs train
      students to ask about tobacco use and to advise quitting, but few programs train
      students to effectively help patients to quit and only 2 programs evaluated the
      competence of all students to provide such training. ADPIE shows promise for
      integrating  tobacco dependence treatment more fully into the clinical training
      of dental hygiene students. Comparison to tooth whitening and fluoride therapy
      training indicated that complexity of the treatment and alignment with dental
      hygiene's mission were themes related to training decisions. CONCLUSION: Full
      implementation of tobacco dependence counseling into dental hygiene education
      requires a commitment by dental hygiene educators to train students and faculty
      in counseling techniques and their evaluation. We identified an existing clinical
      structure as showing promise for facilitating improvement.

PMID- 23116781
TI  - Differentiating programs versus philosophies of care: palliative care and hospice
      are not equal.

PMID- 23116780
TI  - Missed opportunities for providing low-fat dietary advice to people with
      diabetes.
AB  - INTRODUCTION: Because cardiovascular disease is closely linked to diabetes,
      national guidelines recommend low-fat dietary advice for patients who have
      cardiovascular disease or are at risk for diabetes. The prevalence of receiving
      such advice is not known. We assessed the lifetime prevalence rates of receiving
      low-fat dietary advice from a health professional and the relationship between
      having diabetes or risk factors for diabetes and receiving low-fat dietary
      advice. METHODS: From 2002 through 2009, 188,006 adults answered the following
      question in the Medical Expenditure Panel Survey: "Has a doctor or other health
      professional ever advised you to eat fewer high-fat or high-cholesterol foods?"
      We assessed the association between receiving advice and the following
      predictors: a diabetes diagnosis, 7 single risk factors for type 2 diabetes, and
      total number of risk factors. RESULTS: Among respondents without diabetes or risk
      factors for diabetes, 7.4% received low-fat dietary advice; 70.6% of respondents
      with diabetes received advice. Respondents with diabetes were almost twice as
      likely to receive advice as respondents without diabetes or its risk factors. As
      the number of risk factors increased, the likelihood of receiving low-fat dietary
      advice increased. Although unadjusted advice rates increased during the study
      period, the likelihood of receiving advice decreased. CONCLUSION: Although most
      participants with diabetes received low-fat dietary advice, almost one-third did
      not. Low-fat dietary advice was more closely associated with the total number of
      diabetes risk factors than the presence of diabetes. Increasing rates of diabetes
      and diabetes risk factors are outpacing increases in provision of low-fat dietary
      advice.

PMID- 23116782
TI  - Getting around (on four wheels) with a little help from my friends.

PMID- 23116783
TI  - Transitional care for communication impaired older adults: ICU to home.

PMID- 23116784
TI  - Ordering portable x-rays under Medicare: an update and clarification.

PMID- 23116785
TI  - The first influenza pandemic of the 21st century. The REIPI/SEIMC experience.

PMID- 23116786
TI  - Epidemiology of the 2009 influenza pandemic in Spain. The Spanish Influenza
      Surveillance System.
AB  - In accordance with European Centre for Disease Prevention and Control
      recommendations, the Spanish Influenza Surveillance System (SISS) maintained its
      activity during the summer of 2009, and since July 2009 the pandemic virus
      activity was monitored by the SISS. In this paper, we describe the
      epidemiological and virological characteristics of the 2009 pandemic in the Spain
      through the SISS. Spain experienced a transmission of the new A(H1N1)pdm09
      influenza virus during the summer of 2009, which gradually increased, resulting
      in the pandemic wave in early autumn of that year. The reproductive number R0,
      estimated during the growth phase of the pandemic wave (1.32; 95% confidence
      interval [95%CI], 1.29-1.36), showed a transmissibility comparable to preceding
      pandemics. There was an almost complete replacement of the previous seasonal
      A(H1N1) influenza virus by the pandemic virus A(H1N1)pdm09. The pandemic virus
      produced a greater burden of illness than seasonal influenza in children younger
      than 15 years old, while the incidence in those older than 64 years was lower
      compared with previous inter-pandemic seasons. Nevertheless, in Spain the 2009
      pandemic was characterized as mild, considering the duration of the pandemic
      period and the influenza detection rate, both in the range of those observed in
      previous inter-pandemic seasons. Also, the case fatality ratio (CFR) was
      estimated at 0.58 deaths/1,000 confirmed ILI cases (95%CI, 0.52-0.64), in the
      range of the two previous pandemics of 1957 and 1968, with the highest CFR
      observed in the older than 64 years age group. In the 2009 pandemic there was a
      higher percentage of pandemic confirmed deaths in the younger ages, compared to
      seasonal influenza, since only 28% of the reported deaths occurred in persons
      aged 64 years and older.

PMID- 23116787
TI  - Influenza A(H1N1)pdm09 virus: viral characteristics and genetic evolution.
AB  - From April 2009 to the present, the influenza A(H1N1)pdm09 virus has been
      evolving continuously, acquiring new amino acid changes that may alter its
      antigenic characteristics, virulence, and its antiviral drug susceptibility.
      Phylogenetic analysis of the hemagglutinin (HA) gene of A(H1N1)pdm09 viruses
      showed that it clustered into 8 genetic groups relative to A/California/7/2009,
      in addition to others reported by regional influenza surveillance networks.
      However, none were considered antigenically distinct from the vaccine virus
      A/California/7/2009, which was recommended for use during the 2012-2013 influenza
      season in the Northern Hemisphere. Amino acid substitution D222G in the HA1
      subunit of HA was the first potential virulence marker of the influenza
      A(H1N1)pdm09 virus that was associated with severe clinical outcomes. The vast
      majority of influenza A(H1N1)pdm2009 viruses tested by the WHO-GISRS (World
      Health Organization-Global Influenza Surveillance and Response System)
      laboratories were sensitive to neuraminidase inhibitor (NAI) drugs, and during
      the 2011-2012 influenza season the resistance prevalence was low (1%) or
      undetectable in the United States and Europe. Resistance to NAIs was detected
      predominantly in patients with severe conditions, most of whom were
      immunosuppressed. The resistance was usually associated with the H275Y mutation
      in the NA protein sequence, although other amino acid substitutions were also
      reported to confer resistance or decreased susceptibility to 1 or more NAIs.
      Global virological surveillance should be strengthened for new influenza variants
      carrying new mutations or reassorted segments that may affect viral features such
      as virulence, transmission, or antiviral susceptibility.

PMID- 23116788
TI  - Immunopathogenesis of 2009 pandemic influenza.
AB  - Three years after the pandemic, major advances have been made in our
      understanding of the innate and adaptive immune responses to the influenza
      A(H1N1)pdm09 virus and those responses' contribution to the immunopathology
      associated with this infection. Severe disease is characterized by early
      secretion of proinflammatory and immunomodulatory cytokines. This cytokine
      secretion persisted in patients with severe viral pneumonia and was directly
      associated with the degree of viral replication in the respiratory tract.
      Cytokines play important roles in the antiviral defense, but persistent
      hypercytokinemia may cause inflammatory tissue damage and participate in the
      genesis of the respiratory failure observed in these patients. An absence of pre
      existing protective antibodies was the rule for both mild and severe cases. A
      role for pathogenic immunocomplexes has been proposed for this disease. Defective
      T cell responses characterize severe cases of infection caused by the influenza
      A(H1N1)pdm09 virus. Immune alterations associated with accompanying conditions
      such as obesity, pregnancy or chronic obstructive pulmonary disease may interfere
      with the normal development of the specific response to the virus. The role of
      host immunogenetic factors associated with disease severity is also discussed in
      this review. In conclusion, currently available information suggests a complex
      immunological dysfunction/alteration that characterizes the severe cases of 2009
      pandemic influenza. The potential benefits of prophylactic/therapeutic
      interventions aimed at preventing/correcting such dysfunction warrant
      investigation.

PMID- 23116789
TI  - Circulation of other respiratory viruses and viral co-infection during the 2009
      pandemic influenza.
AB  - Coinciding with the pandemic wave of the influenza A(H1N1)pdm09 virus, other
      respiratory viruses have co-circulated in our area and were responsible for many
      acute respiratory infections and influenza-like illness (ILI). Apart from the
      pandemic virus that was responsible for most ILI cases, incidence rates of other
      viruses have varied among geographical areas. In general, human rhinovirus was
      the most frequent among individuals from the community, and respiratory syncytial
      virus among hospitalized patients. Detection rates of other respiratory viruses
      such as human metapneumovirus, adenovirus or parainfluenza viruses have been much
      lower. On the basis of an interference mechanism, human rhinovirus may contribute
      to modulate the pandemic wave, although available data are not conclusive to
      support this hypothesis. In contrast, the epidemic wave of respiratory syncytial
      virus during 2009-2010 was similar to previous seasons. Overall, incidence rates
      of respiratory viruses other than influenza did not change significantly during
      the pandemic season compared to other seasons. No association has been found
      between coinfection of pandemic influenza and other respiratory viruses with the
      prognosis of patients with influenza. The involvement of clinical virology
      laboratories in the etiological diagnosis of ILI cases has improved and has
      optimized diagnostic procedures.

PMID- 23116790
TI  - Pregnancy, obesity and other risk factors for complications in influenza A(H1N1)
      pdm09 infection.
AB  - Although influenza is usually a self-limited disease, patients who develop
      complications are at increased risk of hospitalization, intensive care unit
      admission and death. Since preventive and early therapeutic measures should be
      prioritized in higher risk patients, identification of the risk factors for
      severe infection is important from a public health perspective. Risk factors for
      complications in pandemics may show some differences with regard to seasonal
      influenza. During the influenza A(H1N1)pmd09 pandemic, although many cases
      occurred in younger adults, the risk factors identified for severe infections and
      complications were similar to those for seasonal influenza, including chronic
      respiratory, renal, liver, and heart diseases. Aged patients, although less
      frequently affected, were also at higher risk. Obesity, and particularly morbid
      obesity (>40 body mass index) has been noted as a significant risk factor for
      severe disease in the 2009 influenza pandemic. Some interesting recent studies
      provide insights into the biological reasons behind the poor outcomes in morbidly
      obese patients. In terms of pregnancy, the studies have shown contradictory
      results due to variations in methodology and medical care. However, it seems that
      pregnancy, particularly during the third trimester, increases the risk of
      complications, and that early antiviral treatment is associated with improved
      outcomes.

PMID- 23116791
TI  - The impact of influenza A(H1N1)pdm09 infection on immunosuppressed patients.
AB  - Before the advent of the influenza A(H1N1)pdm virus in 2009, the information
      available about the clinical manifestations and prognosis of influenza in
      immunosuppressed patients was scarce. With the 2009 pandemic, knowledge of the
      behavior, severity and importance of antiviral therapy for influenza A infection
      in immunocompromised hosts has increased considerably. The aim of the present
      manuscript is to review the main challenges of influenza in the most
      representative immunosuppressed populations such as solid organ transplant
      recipients, hematopoietic stem cell transplant recipients, patients with solid
      and hematological cancer and human immunodeficiency virus infected patients.

PMID- 23116792
TI  - Influenza A(H1N1)pdm09-related pneumonia and other complications.
AB  - Influenza A(H1N1)pdm09 virus infection was associated with significant morbidity,
      mainly among children and young adults. The majority of patients had self-limited
      mild-to-moderate uncomplicated disease. However, some patients developed severe
      illness and some died. In addition to respiratory complications, several
      complications due to direct and indirect effects on other body systems were
      associated with influenza A(H1N1)pdm09 virus infection. The main complications
      reported in hospitalized adults with influenza A(H1N1)pdm09 were pneumonia
      (primary influenza pneumonia and concomitant/secondary bacterial pneumonia),
      exacerbations of chronic pulmonary diseases (mainly chronic obstructive pulmonary
      disease and asthma), the need for intensive unit care admission (including
      mechanical ventilation, acute respiratory distress syndrome and septic shock),
      nosocomial infections and acute cardiac events. In experimentally infected
      animals, the level of pulmonary replication of the influenza A(H1N1)pdm09 virus
      was higher than that of seasonal influenza viruses. Pathological studies in
      autopsy specimens indicated that the influenza A(H1N1)pdm09 virus mainly targeted
      the lower respiratory tract, resulting in diffuse alveolar damage (edema, hyaline
      membranes, inflammation, and fibrosis), manifested clinically by severe acute
      respiratory distress syndrome with refractory hypoxemia. Influenza A(H1N1)pdm09
      related pneumonia and other complications were associated with increased
      morbidity and mortality among hospitalized patients.

PMID- 23116793
TI  - Antiviral treatment and vaccination for influenza A(H1N1)pdm09 virus: lessons
      learned from the pandemic.
AB  - The influenza pandemic that was declared by the World Health Organization in June
      2009 created a new scenario for the use of influenza antivirals and vaccination.
      The new strain, influenza A(H1N1)pdm09, was resistant to amantadine and
      rimantadine, and the most frequently used antiviral was oseltamivir. Randomized
      studies were not performed comparing neuraminidase inhibitors with placebo.
      Nevertheless, experience from prospective and retrospective cohorts indicated
      that these drugs were useful for improving the prognosis of patients admitted to
      hospitals, especially for those with more severe disease. Treatment with
      oseltamivir was associated with a reduction in days of fever, length of hospital
      stay, use of mechanical ventilation and mortality. Treatment was more effective
      if it was begun within the first 48 h after the onset of symptoms, but it was
      also useful if begun later. A safe and effective vaccine to prevent disease from
      this new influenza strain was available in developed countries soon after the
      pandemic began; thus, the rate of adverse effects was comparable to that of
      seasonal influenza vaccines. The main barrier to its use was the concern of
      target populations about its necessity and safety. Therefore, the challenges for
      future pandemics will be to increase the population coverage of the vaccine in
      developed countries and to make it affordable for developing countries.

PMID- 23116794
TI  - Influenza A(H1N1)pdm09: beyond the pandemic.
AB  - On August 2010, the World Health Organization declared the end to the 2009
      A(H1N1) pandemic. However, influenza A(H1N1)pdm09 continues to circulate as a
      seasonal virus. Different viruses have predominated in different parts of the
      world. To date, influenza A(H1N1)pdm09 has demonstrated little antigenic drift,
      and its oseltamivir resistance has remained low. In some countries, a higher
      number of severe cases of influenza A(H1N1)pdm09 infection were documented during
      the 2010-2011 season than during the pandemic period. In addition, delays in
      oseltamivir administration, higher ages and comorbidities and low vaccination
      rates in patients with influenza A(H1N1)pdm09 infection were found during the
      first postpandemic season. Therefore, physicians should carefully consider the
      pandemic virus as a possible causative agent in patients with influenza-like
      illnesses admitted to emergency departments. In addition, surveillance systems
      and vaccination campaigns should continue after the pandemic period.

PMID- 23116795
TI  - Slow pace of dietary change in Scotland: 2001-9.
AB  - Monitoring changes in the food and nutrient intake of a nation is important for
      informing the design and evaluation of policy. Surveys of household food
      consumption have been carried out annually in the UK since 1940 and, despite some
      changes over the years 1940-2000, the method used for the Expenditure and Food
      Survey (Living Costs and Food Survey from 2008) has been fundamentally the same
      since 2001. Using these surveys an analytical procedure was devised to compare
      food consumption and nutrient intake in Scotland with the Scottish dietary
      targets, and monitor change. This method takes into account contributions to
      composite foods and losses due to food preparation, as well as inedible and
      edible waste. There were few consistent improvements in consumption of foods or
      nutrients targeted for change over the period 2001-9. A significant but small
      increase was seen in mean fruit and vegetable consumption (259 g/d in 2001, 279
      g/d in 2009, equating to an increase of less than 3 g/person per year). There was
      also a significant decrease in the percentage of food energy from SFA (15.5 % in
      2001, 15.1 % in 2009) and from non-milk extrinsic sugars (15.5 % in 2001, 14.8 %
      in 2009), concurrent with a reduction in whole milk consumption and soft drink
      consumption, respectively. These small changes are encouraging, but highlight the
      time taken for even modest changes in diet to occur. To achieve a significant
      impact on the health of the present Scottish population, the improvements in diet
      will need to be greater and more rapid.

PMID- 23116796
TI  - Application of the van't Hoff dependences in the characterization of molecularly
      imprinted polymers for some phenolic acids.
AB  - Thermodynamic analysis was used to quantify the contribution of entropic and
      enthalpic terms of the binding processes of selected phenolic acids (PAs),
      quercetin and diperodon on series of molecularly imprinted polymers (MIPs). All
      polymers were prepared using acrylamide as functional monomer and acetonitrile as
      a porogen. The following PAs were used as templates - gallic (GA), gentisic
      (GeA), syringic (SyrA), protocatechuic (PCA), 4-hydroxybenzoic (pHBA) and
      vanillic (VA). The assessment was based on quantification by HPLC measurement of
      the analytes tested at temperature range from 20 degrees C to 60 degrees C in two
      mobile phases - methanol and porogen. There were determined van't Hoff curves -
      dependences between logarithms of the retention factors (lnk) and the inverse
      value of the temperature (1/T). All plots fall along straight lines, what
      suggests that there were no changes in the sorption mechanisms over the studied
      temperature range. Determined thermodynamic characteristics helped to specify the
      nature of molecular recognition on the PAs-MIPs. We found that preferred eluent
      for analytes sorption on the PAs-MIPs and the NIP was porogen. When methanol as
      the mobile phase was used there was not documented sorption of the investigated
      compounds on the NIP. Calculated imprinting factors (IFs) in porogen were highest
      in the dominant advantage of template molecules used, what confirmed a good
      molecular imprinting effect. The IF values for PAs studied were as follows:
      GA=21.98+/-2.62, PCA=6.07+/-0.13, pHBA=3.58+/-0.25, SyrA=2.80+/-0.17, GeA=2.37+/
      0.34 and VA=2.07+/-0.10. The results of thermodynamic studies demonstrated that
      enthalpic term was the dominating driving force for the predominant part of
      investigated analytes. The exceptions were: SyrA on the NIP and on the GA-MIP,
      diperodon on the PCA-MIP in acetonitrile and quercetin on the GA-MIP in methanol
      where a favourable driving force was to be found an entropic term. The PAs-MIPs
      and NIP were also characterized by attenuated total reflectance analysis Fourier
      transform infrared spectroscopy (ATR-FTIR) and scanning electron microscopy
      (SEM).

PMID- 23116797
TI  - A comprehensive and suitable method for determining major ions from atmospheric
      particulate matter matrices.
AB  - The present study proposes an analytical methodology that employs ion
      chromatography-conductivity detection for simultaneous quantification of
      inorganic (F(-), Cl(-), NO(3)(-), SO(4)(2-), and PO(3)(-)), monocarboxylate
      (HCOO(-), CH(3)COO(-), propionate, n-butyrate, lactate, and pyruvate),
      dicarboxylate (oxalate and succinate), and tricarboxylate anions (citrate), as
      well as crustal cations (Li(+), Na(+), K(+), NH(4)(+), Ca(2+), Mg(2+)) at low
      pgm(-3) range in airborne particle samples in one single run. The optimized
      conditions for anions were as follows: 0.6 mmol L(-1) KOH for 0-14 min, 0.6-15
      mmol L(-1) KOH 14-20 min, 15-38 mmol L(-1) KOH during 20-32 min and finally
      returned to 0.6 mmol L(-1) for a period of 3 min, thereafter the eluent flow rate
      was 0.38 mL min(-1). Similarly, for cations, isocratic elution was adjusted to
      0.36 mL min(-1) at 17.5 mmol L(-1) H(2)SO(4). LOD ranged 3.0-130 pgm(-3) and LOQ
      was within 10-400 pgm(-3) (Li(+) and PO(4)(3-), respectively) as well as
      recoveries ranged 89% (Ca(2+)) to 120% (Li(+)). Major ions were successfully
      determined in real PM1 and PM2.5 samples. The method used here was found to be a
      comprehensive, simple, cheap and reliable procedure for studying ions in
      particulate matter (PM) samples even those from remote areas or near ecosystem
      natural conditions.

PMID- 23116798
TI  - Analysis of fatty alcohol derivatives with comprehensive two-dimensional liquid
      chromatography coupled with mass spectrometry.
AB  - A simultaneous separation of anionic (fatty alcohol sulfates, fatty alcohol ether
      sulfates), non-ionic (alkyl polyglucosides, fatty alcohol ethoxylates) and
      amphoteric (cocamidopropyl betaines) surfactants was performed by comprehensive
      two-dimensional liquid chromatography (LCxLC) utilizing a ZIC((r))-HILIC column
      in the first dimension, a Reprosphere 100 C8-Aqua column in the second dimension
      and a 10-port two position valve as the interface. The volume of the two sample
      loops were 25 or 50 MUL and allow a one or two minute modulation at a 25 MUL/min
      flow rate. In the first dimension, a gradient of acetonitrile and an ammonium
      acetate buffer was used to separate polyethoxylated surfactants by their degree
      of ethoxylation (EO number) whereas in the second dimension, a separation by
      alkyl chain was performed using a methanol/ammonium acetate buffer gradient. A
      baseline separation of the above mentioned surfactants according to both EO
      number and alkyl chain was achieved. The best performance was used to compare two
      different LCxLC-QTOF MS systems, which demonstrate that a transfer of the method
      from one system to a totally different system is possible. However, because of
      the differences in delay volume and extra-column volume between these systems the
      separation power is changed.

PMID- 23116799
TI  - The mass transfer dynamics of hollow fiber liquid-phase microextraction and its
      application for rapid analysis of biological samples.
AB  - Hollow fiber liquid-phase microextraction (HF-LPME) has been demonstrated to
      potentially become a mainstream sample preparation technique for complex samples.
      Nevertheless, the need for a relatively long extraction time is considered to be
      the major disadvantage of this method. Lengthy extractions may cause the loss of
      the extraction phase and may change the contents of biological samples via the
      action of enzymes. Therefore, control calibrations for particular biological
      systems must be made. In this study, a theoretical model of the mass transfer
      dynamics of two-phase HF-LPME was proposed, and the kinetic calibration (KC) of
      this method for plasma and urine samples was validated. The theoretical results
      were validated by examining the kinetics of the extraction and back-extraction
      processes of HF-LPME. The KC-HF-LPME method was successfully used to correct for
      matrix effects in plasma and urine samples during flunitrazepam analysis. The
      free amount of flunitrazepam was extracted from plasma for 10 min and analyzed by
      gas chromatography/mass spectrometry. The amount of pre-added standard and the
      standard remaining in the extraction phase after extraction were used for the
      quantification of flunitrazepam in plasma and urine samples. The new method not
      only significantly shortens the extraction time but also provides a new
      opportunity to determine the free concentration of analyte in biological systems.

PMID- 23116800
TI  - Rapid metabolite analysis of positron emission tomography radioligands by direct
      plasma injection combining micellar cleanup with high submicellar liquid
      chromatography with radiometric detection.
AB  - A column-switching liquid chromatographic (LC) system was developed for the
      radiometabolite analysis of positron emission tomography (PET) radioligands in
      plasma employing direct injection. This system involves (1) micellar cleanup
      using a short capture column with a micellar mobile phase for submitting plasma
      directly into the system, (2) fast-micellar liquid chromatography utilizing a
      small particle size (2.5 MUm) analysis column under high submicellar condition
      for improving sensitivity, resolution and speed of analysis and (3) highly
      sensitive flow-through beta(+) detection for online measurement of radioligands
      and their radiometabolites. This system enabled highly sensitive radiometric
      analysis at the lowest detection limit of about 1 Becquerel (Bq) for (11)C
      labelled compounds with a high temporal resolution of <4.0 min without any pre
      treatment of plasma. Finally, this novel method could be successfully applied to
      study the radiometabolism for various PET radioligands and provided reliable
      determination in both human and monkey plasma.

PMID- 23116802
TI  - Extension of the carotenoid test to superficially porous C18 bonded phases,
      aromatic ligand types and new classical C18 bonded phases.
AB  - The recent introduction of new stationary phases for liquid chromatography based
      on superficially porous particles, called core-shell or fused-core, dramatically
      improved the separation performances through very high efficiency, due mainly to
      reduced eddy diffusion. However, few studies have evaluated the retention and
      selectivity of C18 phases based on such particles, despite some retention order
      change reported in literature between some of these phases. The carotenoid test
      has been developed a few years ago in the goal to compare the chromatographic
      properties of C18 bonded phases. Based on the analysis of carotenoid pigments by
      using Supercritical Fluid Chromatography (SFC), it allows, with a single
      analysis, to measure three main properties of reversed phase chromatography
      stationary phases: hydrophobicity, polar surface activity and shape selectivity.
      Previous studies showed the effect of the endcapping treatment, the bonding
      density, the pore size, and the type of bonding (monomeric vs. polymeric) on
      these studied properties, and described the classification map used for a direct
      column comparison. It was applied to ten ODS superficially porous stationary
      phases, showing varied chromatographic behaviors amongst these phases. As
      expected, due to the lower specific surface area, these superficially porous
      phases are less hydrophobic than the fully porous one. In regards of the polar
      surface activity (residual silanols) and to the shape selectivity, some of these
      superficially porous phases display close chromatographic properties (Poroshell
      120, Halo C18, Ascentis Express, Accucore C18, Nucleoshell C18 on one side and
      Aeris Wide pore, Aeris peptide and Kinetex XDB on the other side), whereas
      others, Kinetex C18 and Halo peptide ES C18 display more specific ones. Besides,
      they can be compared to classical fully porous phases, in the goal to improve
      method transfer from fully to superficially porous particles. By the way, the
      paper also report the extension of the test to other ligands such as naphtyl,
      cholester, phenyl-hexyl, or to the new ODS bonded phases, such as charge surface
      hybrid phases, High Strength Silica, and Hybrid ones, and also presents results
      for identical brands using different particle size, such as Luna and Synergi
      phases. Phenyl-hexyl and napthyl ligands show rather close properties, low
      hydrophobicity, high polar surface activity and specific shape selectivity,
      whereas, at the opposite, the cholester phase display a polymeric behavior and a
      high hydrophobicity. Finally, additional classical (fully porous particles) C18
      bonded phases are also reported to complete the data set presented in previous
      papers.

PMID- 23116801
TI  - Chromatographic evaluation of a newly designed peptide-silica stationary phase in
      reverse phase liquid chromatography and hydrophilic interaction liquid
      chromatography: mixed mode behavior.
AB  - The short peptide Boc-Phe-Aib-Phe-OH was synthesized and immobilized onto porous
      silica using grafting methodology. The resulting peptide-bonded silica was
      characterized using DRIFT-mode FT-IR, elemental analysis, thermogravimetric
      analysis, solid state C(13) NMR spectroscopy and the successful immobilization of
      the peptide on the silica support was confirmed. This grafted phase was packed
      into a stainless steel column and used for mixed-mode chromatography such as
      reversed-phase high-performance liquid chromatography and hydrophilic interaction
      liquid chromatography for the efficient separation of hydrophobic compounds,
      small polar molecules, and drug molecules. Compared with ODS and phenyl columns,
      this new stationary phase shows considerably higher molecular-planarity
      selectivity towards polyaromatic hydrocarbons and also available for separation
      of nucleo-analytes and sulfa-drug molecules in a hydrophilic interaction liquid
      chromatography mode. The multiple interactions induced by polar carbonyl group
      and hydrophobic phenyl group allow this peptide-modified silica to serve as a
      multi-mode stationary phase in high performance liquid chromatography.

PMID- 23116803
TI  - Micellar electrokinetic chromatography with laser induced detection and liquid
      chromatography tandem mass-spectrometry-based desmosine assays in urine of
      patients with Chronic Obstructive Pulmonary Disease: a comparative analysis.
AB  - Evidences accumulated over the past years that desmosines could be attractive
      indicators of elastic fibre degradation in Chronic Obstructive Pulmonary Disease
      have raised substantial interest with the development of reliable assays to
      measure their concentration in body fluids. It is a firm belief of researchers
      working in this field that accurate assessment of desmosine concentration would
      improve the understanding of elastin metabolism disorders and allow these cross
      links to become a useful tool in the diagnosis and clinical management of these
      diseases. From among the variety of techniques available on the market, HPLC; CE
      and LC-MS have proved to be successful tools for measuring desmosines in
      biological fluids. However, differences in the analytical performance of methods
      may hinder the comparability of data, thus limiting the analytical strength and
      clinical utility of methods themselves. To address the relative contribution of
      different factors to the exact quantification of desmosines, the full potential
      of MEKC-LIF and LC-MS, the two systems that better than others offer more
      selective and sensitive detection for desmosine analysis, was studied on 56 urine
      samples. The results of this systematic comparative study underline the
      significant benefits of LC-MS over MEKC-LIF in terms of precision and
      sensitivity. Nevertheless, MEKC-LIF could be an attractive alternative in routine
      laboratories lacking the LC-MS instrumentation and skills to run these methods.

PMID- 23116804
TI  - Polarity-adjustable reversed phase ultrathin-layer chromatography.
AB  - Reversed phase thin layer chromatography (TLC) or high performance thin layer
      chromatography (HPTLC) plates modified with C18, C8 or C2 to provide the silica
      gel stationary phase with different polarities are available on the market,
      however, reversed phase plates with tunable polarity have not been reported.
      Given the limited variety of reversed phase plates, mobile phase composition
      optimization is necessary to obtain better separation of analytes with similar
      characteristics, which is often a time consuming step. We present polarity
      adjustable reversed phase ultrathin-layer chromatography (UTLC) plates, which
      simplifies the mobile phase screening process and greatly expands the selection
      of reversed phase plates. The plates were fabricated on glass substrates with
      SiO(2) nanopillars deposited using the glancing angle deposition (GLAD)
      technique. SiO(2) nanopillars were functionalized with octadecyltrichlorosilane
      to generate a super hydrophobic stationary phase. Unlike commercial silica-gel
      based stationary phases, the isolated nanopillar architecture presented here
      exposes a high surface area to post-fabrication surface treatments. In our work,
      an O(2) plasma treatment at different powers, pressures and exposure times was
      used to shorten the silane carbon chain and introduce COOH groups to the surface,
      producing plates with finely tunable polarities. Separation of a model dye
      mixture of Sudan blue and Sudan IV confirmed the tuning of surface polarities by
      measurement of retention behavior changes. The dye elution order reversed as a
      result of the change in surface polarity. When the same plasma treatment process
      was tested on commercial reversed phase plates, separation behavior did not
      change because the disordered and tortuous silica gel restricts the accessible
      surface area. Plasma treatment of GLAD structures with highly accessible surfaces
      improved control over interfacial properties, producing better reverse phase
      separations.

PMID- 23116805
TI  - Assessment of impact factors on shear wave based liver stiffness measurement.
AB  - Shear wave based ultrasound elastographies have been implemented as non-invasive
      methods for quantitative assessment of liver stiffness. Nonetheless, there are
      only a few studies that have investigated impact factors on liver stiffness
      measurement (LSM). Moreover, standard examination protocols for LSM are still
      lacking in clinical practice. Our study aimed to assess the impact factors on LSM
      to establish its standard examination protocols in clinical practice. We applied
      shear wave based elastography point quantification (ElastPQ) in 21 healthy
      individuals to determine the impact of liver location (segments I-VIII),
      breathing phase (end-inspiration and end-expiration), probe position (sub-costal
      and inter-costal position) and examiner on LSM. Additional studies in 175 healthy
      individuals were also performed to determine the influence of gender and age on
      liver stiffness. We found significant impact of liver location on LSM, while the
      liver segment V displayed the lowest coefficient of variation (CV 21%). The liver
      stiffness at the end-expiration was significantly higher than that at the end
      inspiration (P=2.1E-05). The liver stiffness was 8% higher in men than in women
      (3.8 +/- 0.7 kPa vs. 3.5 +/- 0.4 kPa, P=0.0168). In contrast, the liver stiffness
      was comparable in the different probe positions, examiners and age groups
      (P>0.05). In conclusion, this study reveals significant impact from liver
      location, breathing phase and gender on LSM, while furthermore strengthening the
      necessity for the development of standard examination protocols on LSM.

PMID- 23116806
TI  - Characterization of hepatic lesions (<= 30 mm) with liver-specific contrast
      agents: a comparison between ultrasound and magnetic resonance imaging.
AB  - PURPOSE: Imaging-based differentiation of hepatic lesions (<= 30 mm) between well
      differentiated hepatocellular carcinomas (w-HCC) and regenerative nodules (RN)
      presents difficulties. The aim was to compare the diagnostic abilities to
      differentiate w-HCC from RN using contrast-enhanced ultrasound and magnetic
      resonance imaging (MRI) both with liver-specific contrast agents. MATERIALS AND
      METHODS: This prospective study included 67 pathologically proven hepatic lesions
      (17.5 +/- 5.4mm, 54 w-HCCs, 13 RNs) in 56 patients with chronic
      hepatitis/cirrhosis (male 40, female 16; 29-79y). Hepatic-arterial/liver-specific
      phase enhancements were assessed quantitatively by ultrasound with perflubutane
      microbubble agent and MRI with gadolinium-ethoxybenzyl-diethylenetriamine with
      respect to the histological findings. RESULTS: Sensitivity, specificity and
      accuracy of hepatic-arterial phase hyper-enhancement for w-HCC were 59.3%, 100%
      and 67.2% by ultrasound and 46.3%, 100% and 56.7% by MRI without significant
      difference. Meanwhile, those of liver-specific-phase hypo-enhancement for w-HCC
      were 44.4%, 100% and 55.2% by ultrasound and 87.0% (p<0.0001), 46.2% (p=0.0052)
      and 79.1% (p=0.0032) by MRI. Diagnostic accuracies for w-HCC by area under the
      receiver operating characteristic curves were higher in the hepatic-arterial
      phase in ultrasound (0.8316) than MRI (0.6659, p=0.0101) and similar in the liver
      specific phase in ultrasound (0.7225) and MRI (0.7347, p=0.8814). CONCLUSIONS:
      Hypervascularity is a significant feature which distinguishes w-HCC from RN, and
      ultrasound exerts a beneficial impact better than MRI for such characterization.
      However, both imaging have comparable abilities in the characterization of non
      hypervascular lesions, compensating mutually for the poor sensitivity of
      ultrasound and the poor specificity of MRI in the liver-specific phase.

PMID- 23116807
TI  - Quantification of coronary artery stenosis with high-resolution CT in comparison
      with histopathology in an ex vivo study.
AB  - PURPOSE: To investigate the ex vivo performance of high-resolution computed
      tomography (CT) for quantitative assessment of percentage diameter stenosis in
      coronary arteries compared to histopathology. MATERIALS AND METHODS: High
      resolution CT was performed in 26 human heart specimens after the injection of
      iodinated contrast media into the coronary arteries. Coronary artery plaques were
      visually identified on CT images and the grade of stenosis for each plaque was
      measured with electronic calipers. All coronary plaques were characterized by
      histopathology according to the Stary classification, and the percentage of
      stenosis was measured. RESULTS: CT depicted 84% (274/326) of all coronary plaques
      identified by histology. Missed plaques by CT were of Stary type I (n=31), type
      II (n=16), and type III (n=5). The stenosis degree significantly correlated
      between CT and histology (r=0.81, p<0.001). CT systematically overestimated the
      stenosis of calcified plaques (mean difference - 11.0 +/- 9.5%, p<0.01) and
      systematically underestimated the stenosis of non-calcified plaques (mean
      difference -6.8 +/- 10.4%, p<0.05), while there was no significant difference for
      mixed-type plaques (mean difference -0.4 +/- 11.7%, p=0.85). There was a
      significant underestimation of stenosis degree as measured by CT for Stary II
      plaques (mean difference -14 +/- 9%, p<0.01) and a significant overestimation for
      Stary VII plaques (mean difference 9 +/- 10%, p<0.05), but there was no
      significant difference in stenosis degree between both modalities for other
      plaque types. CONCLUSIONS: High-resolution CT reliably depicts advanced stage
      coronary plaques with an overall good correlation of stenosis degree compared to
      histology, however, the degree of stenosis is systematically overestimated in
      calcified and underestimated in non-calcified plaques.

PMID- 23116808
TI  - Comment on: a meta-analysis of common risk factors associated with the diagnosis
      of developmental dysplasia of the hip in newborns.

PMID- 23116809
TI  - Imaging techniques in the assessment of sternal fracture patients.

PMID- 23116810
TI  - Abnormal amplitude low-frequency oscillations in medication-naive, first-episode
      patients with major depressive disorder: a resting-state fMRI study.
AB  - BACKGROUND: Recent resting-state fMRI studies on major depressive disorder (MDD)
      have found altered temporal correlation between low-frequency oscillations
      (LFOs). However, changes on the amplitudes of these LFOs remain largely unknown.
      METHODS: Twenty-two medication-naive, first-episode patients with MDD and 19 age
      , sex-, education-matched healthy controls were recruited. Resting-state fMRI was
      obtained by using an echo-planar imaging sequence and the fractional amplitude of
      low-frequency fluctuations (fALFF) was calculated to investigate the amplitude of
      LFOs in the resting state. RESULTS: Compared with control subjects, patients with
      MDD showed significantly decreased fALFF in right cerebellum posterior lobe, left
      parahippocampal gyrus and right middle frontal gyrus and increased fALFF in left
      superior occipital gyrus/cuneus (p<0.05, corrected for multiple comparisons).
      Further receiver operating characteristic curves (ROC) analyses suggested that
      the alterations of fALFF in these regions might be used as markers to classify
      patients with MDD from healthy controls. CONCLUSIONS: These findings indicated
      LFOs abnormalities in MDD and the fALFF analysis might be a potential approach in
      further exploration of this disorder.

PMID- 23116811
TI  - Using the Edinburgh postnatal depression scale to screen for anxiety disorders:
      conceptual and methodological considerations.
AB  - BACKGROUND: Perinatal anxiety symptoms and disorders are prevalent and disabling
      but have not to date been a focus for specific clinical and public health
      attention. The EPDS is widely used to detect probable depression, and many
      studies have also found that three items from this scale load on an anxiety
      factor, in both the antenatal and postnatal periods. In addition, studies have
      found clinically significant correlations between the EPDS and various anxiety
      specific measures in the perinatal period. The aim of this paper is to examine
      studies which address the capacity of the EPDS to detect anxiety disorders, to
      assess whether the EPDS performs differently in women with depressive or anxiety
      disorders and to consider the implications for future research and clinical
      practice. METHODS: The English-language perinatal mental health literature was
      searched. Six studies with data pertaining to the capacity of the EPDS to detect
      perinatal anxiety disorders in women were identified. These studies provide
      information on i) comparison of total EPDS score by diagnoses of anxiety and
      depression and ii) comparison of the anxiety subscale score (EPDS-3A) by
      diagnoses of anxiety and depression. RESULTS: There is evidence from both sets of
      information that the EPDS is useful for screening for anxiety in women and
      emerging evidence that Total EPDS and EPDS-3A can distinguish depression from
      anxiety reliably. LIMITATIONS: The findings are based on a small number of
      studies, conducted in a variety of clinical and community settings in different
      languages and countries, and with variable sample sizes, some of which lack power
      to ensure reliable conclusions. CONCLUSIONS: The EPDS appears to detect perinatal
      anxiety disorders, but further research is required to establish the clinical and
      public health value of the EPDS for this purpose, and whether it has more robust
      psychometric properties or is more feasible and acceptable than existing anxiety
      specific measures.

PMID- 23116812
TI  - Mapping the hand, foot and face representations in the primary motor cortex -
      retest reliability of neuronavigated TMS versus functional MRI.
AB  - INTRODUCTION: Functional magnetic resonance imaging (fMRI) is a frequently used
      non-invasive mapping technique for investigating the human motor system.
      Recently, neuronavigated transcranial magnetic stimulation (nTMS) has been
      established as an alternative approach. We here compared the test-retest
      reliability of both mapping techniques with regard to the cortical
      representations of the hand, leg, face and tongue areas. METHODS: Ten healthy
      subjects were examined three times (intervals: 3-5days/21-35days) with fMRI and
      nTMS. Motor-evoked potentials were recorded from the abductor pollicis brevis,
      plantaris, mentalis and the tongue muscles. The same muscles were activated in an
      fMRI motor task. Euclidean distances (ED) between hotspots and centers of gravity
      (CoG) were computed for the respective somatotopic representations. Furthermore,
      spatial reliability was tested by intersession overlap volumes (OV) and voxel
      wise intraclass correlations (ICC). RESULTS: Feasibility of fMRI was 100% for all
      body parts and sessions. In contrast, nTMS was feasible in all sessions and
      subjects only for the hand area, while mappings of the foot (90%), face (70%) and
      tongue representations (40%) remained incomplete in several subjects due to
      technical constraints and co-stimulation artifacts. On average, the mean ED of
      the hotspots was better for fMRI (6.2+/-1.1mm) compared to nTMS (10.8+/-1.9mm)
      while stability of CoG was similar for both methods. Peak voxel reliability (ICC)
      was high for both methods (>0.8), and there was no influence of inter-session
      intervals. In contrast, the reliability of mapping the spatial extent of the
      hand, foot, lips and tongue representations was poor to moderate for both fMRI
      and nTMS (OVs and ICC<50%). Especially nTMS mappings of the face and tongue areas
      yielded poor reliability estimates. CONCLUSION: Both methods are highly reliable
      when mapping the core region of a given target muscle, especially for the hand
      representation area. In contrast, mapping the spatial extent of a cortical
      representation area was only little reliable for both nTMS and fMRI. In summary,
      fMRI was better suited when mapping motor representations of the head, while nTMS
      showed equal reliability for mapping the hand and foot representation areas.
      Hence, both methods may well complement each other.

PMID- 23116813
TI  - Spatiotemporal multi-resolution approximation of the Amari type neural field
      model.
AB  - Neural fields are spatially continuous state variables described by integro
      differential equations, which are well suited to describe the spatiotemporal
      evolution of cortical activations on multiple scales. Here we develop a multi
      resolution approximation (MRA) framework for the integro-difference equation
      (IDE) neural field model based on semi-orthogonal cardinal B-spline wavelets. In
      this way, a flexible framework is created, whereby both macroscopic and
      microscopic behavior of the system can be represented simultaneously. State and
      parameter estimation is performed using the expectation maximization (EM)
      algorithm. A synthetic example is provided to demonstrate the framework. 

PMID- 23116814
TI  - The time course of shape discrimination in the human brain.
AB  - The lateral occipital cortex (LOC) activates selectively to images of intact
      objects versus scrambled controls, is selective for the figure-ground
      relationship of a scene, and exhibits at least some degree of invariance for size
      and position. Because of these attributes, it is considered to be a crucial part
      of the object recognition pathway. Here we show that human LOC is critically
      involved in perceptual decisions about object shape. High-density EEG was
      recorded while subjects performed a threshold-level shape discrimination task on
      texture-defined figures segmented by either phase or orientation cues. The
      appearance or disappearance of a figure region from a uniform background
      generated robust visual evoked potentials throughout retinotopic cortex as
      determined by inverse modeling of the scalp voltage distribution. Contrasting
      responses from trials containing shape changes that were correctly detected
      (hits) with trials in which no change occurred (correct rejects) revealed
      stimulus-locked, target-selective activity in the occipital visual areas LOC and
      V4 preceding the subject's response. Activity that was locked to the subjects'
      reaction time was present in the LOC. Response-locked activity in the LOC was
      determined to be related to shape discrimination for several reasons: shape
      selective responses were silenced when subjects viewed identical stimuli but
      their attention was directed away from the shapes to a demanding letter
      discrimination task; shape-selectivity was present across four different stimulus
      configurations used to define the figure; LOC responses correlated with
      participants' reaction times. These results indicate that decision-related
      activity is present in the LOC when subjects are engaged in threshold-level shape
      discriminations.

PMID- 23116815
TI  - Processing of speech and non-speech sounds in the supratemporal plane: auditory
      input preference does not predict sensitivity to statistical structure.
AB  - The supratemporal plane contains several functionally heterogeneous subregions
      that respond strongly to speech. Much of the prior work on the issue of speech
      processing in the supratemporal plane has focused on neural responses to single
      speech vs. non-speech sounds rather than focusing on higher-level computations
      that are required to process more complex auditory sequences. Here we examined
      how information is integrated over time for speech and non-speech sounds by
      quantifying the BOLD fMRI response to stochastic (non-deterministic) sequences of
      speech and non-speech naturalistic sounds that varied in their statistical
      structure (from random to highly structured sequences) during passive listening.
      Behaviorally, the participants were accurate in segmenting speech and non-speech
      sequences, though they were more accurate for speech. Several supratemporal
      regions showed increased activation magnitude for speech sequences (preference),
      but, importantly, this did not predict sensitivity to statistical structure: (i)
      several areas showing a speech preference were sensitive to statistical structure
      in both speech and non-speech sequences, and (ii) several regions that responded
      to both speech and non-speech sounds showed distinct responses to statistical
      structure in speech and non-speech sequences. While the behavioral findings
      highlight the tight relation between statistical structure and segmentation
      processes, the neuroimaging results suggest that the supratemporal plane mediates
      complex statistical processing for both speech and non-speech sequences and
      emphasize the importance of studying the neurocomputations associated with
      auditory sequence processing. These findings identify new partitions of
      functionally distinct areas in the supratemporal plane that cannot be evoked by
      single stimuli. The findings demonstrate the importance of going beyond input
      preference to examine the neural computations implemented in the superior
      temporal plane. 

PMID- 23116816
TI  - The structural, connectomic and network covariance of the human brain.
AB  - Though it is widely appreciated that complex structural, functional and
      morphological relationships exist between distinct areas of the human cerebral
      cortex, the extent to which such relationships coincide remains insufficiently
      appreciated. Here we determine the extent to which correlations between brain
      regions are modulated by either structural, connectomic or network-theoretic
      properties using a structural neuroimaging data set of magnetic resonance imaging
      (MRI) and diffusion tensor imaging (DTI) volumes acquired from N=110 healthy
      human adults. To identify the linear relationships between all available pairs of
      regions, we use canonical correlation analysis to test whether a statistically
      significant correlation exists between each pair of cortical parcels as
      quantified via structural, connectomic or network-theoretic measures. In addition
      to this, we investigate (1) how each group of canonical variables (whether
      structural, connectomic or network-theoretic) contributes to the overall
      correlation and, additionally, (2) whether each individual variable makes a
      significant contribution to the test of the omnibus null hypothesis according to
      which no correlation between regions exists across subjects. We find that,
      although region-to-region correlations are extensively modulated by structural
      and connectomic measures, there are appreciable differences in how these two
      groups of measures drive inter-regional correlation patterns. Additionally, our
      results indicate that the network-theoretic properties of the cortex are strong
      modulators of region-to-region covariance. Our findings are useful for
      understanding the structural and connectomic relationship between various parts
      of the brain, and can inform theoretical and computational models of cortical
      information processing. 

PMID- 23116817
TI  - Imaging neural architecture of the brain based on its multipole magnetic
      response.
AB  - Although magnetic fields interact weakly with biological tissues, at high fields,
      this interaction is sufficiently strong to cause measurable shifts in the Larmor
      frequency among various tissue types. While measuring frequency shift and its
      anisotropy has enabled NMR spectroscopy to determine structures of large
      molecules, MRI has not been able to fully utilize the vast information existing
      in the frequency to elucidate tissue microstructure. Using a multipole analysis
      of the complex MRI signal in the Fourier spectral space, we developed a fast and
      high-resolution method that enables the quantification of tissue's magnetic
      response with a set of magnetic susceptibility tensors of various ranks. The
      Fourier spectral space, termed p-space, can be generated by applying field
      gradients or equivalently by shifting the k-space data in various directions.
      Measuring these tensors allows the visualization and quantification of tissue
      architecture. We performed 3D whole-brain multipole susceptibility tensor imaging
      in simulation, on intact mouse brains ex vivo and on human brains in vivo. We
      showed that these multipole susceptibility tensors can be used to image
      orientations of ordered white matter fibers. These experiments demonstrate that
      multipole tensor analysis may enable practical mapping of tissue microstructure
      in vivo without rotating subject or magnetic field.

PMID- 23116818
TI  - Postoperative spinal deformity after treatment of intracanal spine lesions.
AB  - BACKGROUND CONTEXT: Surgical treatment of intracanal (both intramedullary and
      extramedullary) spine lesions requires posterior decompressive techniques in
      nearly all instances. Postoperative spinal deformities, most notably sagittal and
      coronal decompensation, are of significant concern for both the patient and the
      spinal surgeon. PURPOSE: To review and define principles and features of spinal
      deformities after posterior spinal decompression for intracanal spinal lesions,
      and to define patients who may benefit from the concomitant spinal fusion.
      METHODS: A systematic review of MEDLINE was conducted, including articles
      published between 1980 and 2011. Articles related to spinal deformities after
      posterior decompression for the treatment of intracanal spine lesions were
      identified. RESULTS: Ten articles met all inclusion and exclusion criteria. All
      were case series with limited evidence (Level IV). Many risk factors to deformity
      were implied but with limited evidence. Young age was the most commonly
      identified risk in these articles. CONCLUSIONS: Spinal deformity after posterior
      decompression is a common complication, most notably in children and young
      adults, after the removal of intramedullary tumors. Many risk factors have been
      implied to increase the postoperative development of spinal deformity, including
      young age, laminectomy extension, preoperative deformity, and extensive facet
      resection, among others. However, there is a lack of high-quality evidence to
      propose an algorithm for treatment or preventive measures. New studies with
      larger series of patients and standardized clinical outcomes are necessary to
      establish optimal treatment protocols.

PMID- 23116819
TI  - Bioethanol production using carbohydrate-rich microalgae biomass as feedstock.
AB  - This study aimed to evaluate the potential of using a carbohydrate-rich microalga
      Chlorella vulgaris FSP-E as feedstock for bioethanol production via various
      hydrolysis strategies and fermentation processes. Enzymatic hydrolysis of C.
      vulgaris FSP-E biomass (containing 51% carbohydrate per dry weight) gave a
      glucose yield of 90.4% (or 0.461 g (g biomass)(-1)). The SHF and SSF processes
      converted the enzymatic microalgae hydrolysate into ethanol with a 79.9% and
      92.3% theoretical yield, respectively. Dilute acidic hydrolysis with 1% sulfuric
      acid was also very effective in saccharifying C. vulgaris FSP-E biomass,
      achieving a glucose yield of nearly 93.6% from the microalgal carbohydrates at a
      starting biomass concentration of 50 g L(-1). Using the acidic hydrolysate of C.
      vulgaris FSP-E biomass as feedstock, the SHF process produced ethanol at a
      concentration of 11.7 g L(-1) and an 87.6% theoretical yield. These findings
      indicate the feasibility of using carbohydrate-producing microalgae as feedstock
      for fermentative bioethanol production.

PMID- 23116820
TI  - Cultivation of a microalga Chlorella vulgaris using recycled aqueous phase
      nutrients from hydrothermal carbonization process.
AB  - This study investigated the feasibility of using recovered nutrients from
      hydrothermal carbonization (HTC) for cultivation of microalga Chlorella vulgaris.
      Different dilution multiples of 50, 100 and 200 were applied to the recycled
      process water from HTC and algal growth was compared among these media and a
      standard growth medium BG-11. Algae achieved a biomass concentration of 0.79 g/L
      on 50 * process water after 4 days. Algae removed total nitrogen, total
      phosphorus and chemical oxygen demand by 45.5-59.9%, 85.8-94.6% and 50.0-60.9%,
      respectively, on differently diluted process water. The fatty acid methyl ester
      yields for algae grown on the process water were 11.2% (50 *), 11.2% (100 *) and
      9.7% (200 *), which were significantly higher than 4.5% for BG-11. In addition,
      algae cultivated on process water had 18.9% higher carbon and 7.8% lower nitrogen
      contents than those on BG-11, indicating that they are very suitable as biofuel
      feedstocks.

PMID- 23116821
TI  - Cis-9,trans-11-conjugated linoleic acid affects lipid raft composition and
      sensitizes human colorectal adenocarcinoma HT-29 cells to X-radiation.
AB  - BACKGROUND: Investigations concerned the mechanism of HT-29 cells
      radiosensitization by cis-9,trans-11-conjugated linoleic acid (c9,t11-CLA), a
      natural component of human diet with proven antitumor activity. METHODS: The
      cells were incubated for 24h with 70MUM c9,t11-CLA and then X-irradiated. The
      following methods were used: gas chromatography (incorporation of the CLA
      isomer), flow cytometry (cell cycle), cloning (survival), Western blotting
      (protein distribution in membrane fractions), and pulse-field gel electrophoresis
      (rejoining of DNA double-strand breaks). In parallel, DNA-PK activity, gamma-H2AX
      foci numbers and chromatid fragmentation were estimated. Gene expression was
      analysed by RT-PCR and chromosomal aberrations by the mFISH method. Nuclear
      accumulation of the EGF receptor (EGFR) was monitored by ELISA. RESULTS AND
      CONCLUSIONS: C9,t11-CLA sensitized HT-29 cells to X-radiation. This effect was
      not due to changes in cell cycle progression or DNA-repair-related gene
      expression. Post-irradiation DSB rejoining was delayed, corresponding with the
      insufficient DNA-PK activation, although chromosomal aberration frequencies did
      not increase. Distributions of cholesterol and caveolin-1 in cellular membrane
      fractions changed. The nuclear EGFR translocation, necessary to increase the DNA
      PK activity in response to oxidative stress, was blocked. We suppose that c9,t11
      CLA modified the membrane structure, thus disturbing the intracellular EGFR
      transport and the EGFR-dependent pro-survival signalling, both functionally
      associated with lipid raft properties. GENERAL SIGNIFICANCE: The results point to
      the importance of the cell membrane interactions with the nucleus after injury
      inflicted by X -rays. Compounds like c9,t11-CLA, that specifically alter membrane
      properties, could be used to develop new anticancer strategies.

PMID- 23116822
TI  - Evolutionary entropy predicts the outcome of selection: Competition for resources
      that vary in abundance and diversity.
AB  - Competition between individuals for resources which are limited and diverse in
      composition is the ultimate driving force of evolution. Classical studies of this
      event contend that the outcome is a deterministic process predicted by the growth
      rate of the competing types-a tenet called the Malthusian selection principle.
      Recent studies of competition indicate that the dynamics of selection is a
      stochastic process, regulated by the population size, the abundance and diversity
      of the resource, and predicted by evolutionary entropy-a statistical parameter
      which characterizes the rate at which the population returns to the steady state
      condition after a random endogenous or exogenous perturbation. This tenet, which
      we will call the entropic selection principle entails the following relations: 
      This article delineates the analytic, computational and empirical support for
      this tenet. We show moreover that the Malthusian selection principle, a
      cornerstone of classical evolutionary genetics, is the limit, as population size
      and resource abundance tends to infinity of the entropic selection principle. The
      Malthusian tenet is an approximation to the entropic selection principle-an
      approximation whose validity increases with increasing population size and
      increasing resource abundance. Evolutionary entropy is a generic concept that
      characterizes the interaction dynamics of metabolic entities at several levels of
      biological organization: cellular, organismic and ecological. Accordingly, the
      entropic selection principle represents a general rule for explaining the
      processes of adaptation and evolution at each of these levels.

PMID- 23116824
TI  - The effect of threat on attentional interruption by pain.
AB  - Pain is known to interrupt attention. This interruption is highly sensitive to
      the extent of involvement of both attentional control and the level of threat
      associated with the sensation. However, few studies have examined these factors
      together. This study aimed to examine the interruptive effect of pain on higher
      order attentional tasks under conditions of low and high threat. Fifty
      participants completed an n-back task, an attentional switching task, and a
      divided attention task, once in pain and once without pain. Twenty-five
      participants were given standard task instructions (control condition), and the
      remainder were given additional verbal information designed to increase threat
      (threat condition). Pain interrupted participant performance on both the n-back
      and attentional switching task, but not on the divided attention task. The
      addition of the threat manipulation did not seem to significantly alter the
      effect of pain on these attentional tasks. However, independent of pain, threat
      did moderate performance on the divided attention task. These findings support
      the robustness of the effect of pain on performance on higher-order attention
      tasks. Future research is needed to examine what factors alter the cognitive
      interruption caused by pain.

PMID- 23116825
TI  - Assessment of the LuminoTox leachate phase assay as a complement to the LuminoTox
      solid phase assay: effect of fine particles in natural sediments.
AB  - The LuminoTox solid phase assay (Lum-SPA), developed to assess the potential
      ecotoxicity of natural polluted sediments, employs stabilized thylakoids isolated
      from spinach plant extracts. When thylakoids are exposed to polluted samples, the
      action of pollutants can interfere with transmission of chlorophyll fluorescence
      linked to Photosystems I and II, causing a decrease in fluorescence emission. To
      differentiate between bulk and leachate effects, we developed a complementary
      assay of the Lum-SPA named the LuminoTox leachate phase assay (Lum-LPA). Twelve
      natural sediments were selected on the basis of their potential ecotoxicity and
      different quantities of fines. Results showed that in the Lum-LPA, the IC50s were
      always lower than those observed in the Lum-SPA. Significant inverse correlations
      were found between the IC50s obtained with the Lum-SPA and the percentage of
      fines (silt+clay fraction). In order to identify the cause of the higher
      ecotoxicity found in the Lum-LPA, we tested the supernatant of the liquid phase
      recovered after centrifugation (3000 g), and it appeared far less toxic than the
      Lum-LPA filtrates. To confirm the hypothesis that sensitivity in the Lum-LPA
      could be due to the presence of very fine particles, Photosynthetic Enzyme
      Complexes (PECs) were exposed to two kinds of clay materials with and without
      copper (0.6 mg L(-1)). Similar results were obtained in the Lum-LPA for both
      cases, revealing the sensitivity of this test to very fine particles.

PMID- 23116823
TI  - Recreational physical activity and risk of papillary thyroid cancer among women
      in the California Teachers Study.
AB  - PURPOSE: Little is known about the relationship between physical activity and
      thyroid cancer risk, and few cohort data on this association exist. Thus, the
      present study aimed to prospectively examine long-term activity and risk of
      papillary thyroid cancer among women. METHODS: 116,939 women in the California
      Teachers Study, aged 22-79 years with no history of thyroid cancer at cohort
      entry, were followed from 1995-1996 through 2009; 275 were diagnosed with
      invasive papillary thyroid cancer. Cox proportional-hazards regression provided
      relative risk (RR) estimates and 95% confidence intervals (CI) for associations
      between thyroid cancer and combined strenuous and moderate recreational physical
      activity both in the long-term (high school through age 54 years or current age
      if younger than 54 years) and recently (during the three years prior to joining
      the cohort). RESULTS: Overall, women whose long-term recreational physical
      activity averaged at least 5.5 MET-hours/week (i.e. were active) had a non
      significant 23% lower risk of papillary thyroid cancer than inactive women (RR =
      0.77, 95% CI: 0.57, 1.04). RR estimates were stronger among normal weight or
      underweight women (body mass index, BMI<25.0 kg/m(2), trend p = 0.03) than among
      overweight or obese women (trend p = 0.35; homogeneity-of-trends p = 0.03). A
      similar pattern of risk was observed for recent activity (BMI<25 kg/m(2), trend p
      = 0.11; BMI>=25 kg/m(2), trend p = 0.16; homogeneity-of-trends p = 0.04).
      Associations for long-term activity did not appear to be driven by activity in
      any particular life period (e.g. youth, adulthood). CONCLUSIONS: Long-term
      physical activity may reduce papillary thyroid cancer risk among normal weight
      and underweight women.

PMID- 23116826
TI  - Performance evaluation of a bipolar electrolysis/electrocoagulation (EL/EC)
      reactor to enhance the sludge dewaterability.
AB  - The present study aimed to evaluate the performance of a bipolar
      electrolysis/electrocoagulation reactor designed to enhance the sludge
      dewaterability. The reactor was 15 L in volume, with two series of plates used in
      it; Ti/RuO(2) plates for the electrolysis of the sludge, and also aluminum and
      iron plates for electrocoagulation process. The dewaterability of the sludge was
      determined in terms of its capillary suction time (CST) and specific resistance
      to filtration (SRF), while the degree of sludge disintegration was determined
      based on the value of degree of sludge disintegration (DD(SCOD)). The maximum
      reduction in CST and SRF was observed at a detention time of 20 min and a voltage
      of 30 V. However, increasing of both detention time and voltage significantly
      increased the values of CST and SRF even to an extent that they both exceeded
      those of the untreated sludge. The optimal degree of sludge disintegration
      achieved by the present study was 2.5%, which was also achieved at a detention
      time of 20 min and a voltage of 30V. As reported previously, increased DD(SCOD)
      values led to increasing CST and SRF values, due primarily to the disruption of
      the sludge flocs. According to the results from the present study, it can be
      concluded that simultaneous application of electrocoagulation and electrolysis is
      effective in enhancing the sludge dewaterability, because electrocoagulation
      helps to achieve a higher degree of sludge disintegration while maintaining the
      desired sludge dewaterability.

PMID- 23116827
TI  - Evaluation of ion exchange resins for the removal of dissolved organic matter
      from biologically treated paper mill effluent.
AB  - In this study, the efficiency of six ion exchange resins to reduce the dissolved
      organic matter (DOM) from a biologically treated newsprint mill effluent was
      evaluated and the dominant removal mechanism of residual organics was established
      using advanced organic characterisations techniques. Among the resins screened,
      TAN1 possessed favourable Freundlich parameters, high resin capacity and solute
      affinity, closely followed by Marathon MSA and Marathon WBA. The removal
      efficiency of colour and lignin residuals was generally good for the anion
      exchange resins, greater than 50% and 75% respectively. In terms of the DOM
      fractions removal measured through liquid chromatography-organic carbon and
      nitrogen detector (LC-OCND), the resins mainly targeted the removal of humic and
      fulvic acids of molecular weight ranging between 500 and 1000 g mol(-1), the
      portion expected to contribute the most to the aromaticity of the effluent. For
      the anion exchange resins, physical adsorption operated along with ion exchange
      mechanism assisting to remove neutral and transphilic acid fractions of DOM. The
      column studies confirmed TAN1 being the best of those screened, exhibited the
      longest mass transfer zone and maximum treatable volume of effluent. The
      treatable effluent volume with 50% reduction in dissolved organic carbon (DOC)
      was 4.8 L for TAN1 followed by Marathon MSA - 3.6L, Marathon 11 - 2.0 L, 21K-XLT 
      1.5 L and Marathon WBA - 1.2 L. The cation exchange resin G26 was not effective
      in DOM removal as the maximum DOC removal obtained was only 27%. The resin
      capacity could not be completely restored for any of the resins; however, a
      maximum restoration up to 74% and 93% was achieved for TAN1 and Marathon WBA
      resins. While this feasibility study indicates the potential option of using ion
      exchange resins for the reclamation of paper mill effluent, the need for
      improving the regeneration protocols to restore the resin efficiency is also
      identified. Similarly, care should be taken while employing LC-OCND for
      characterising resin-treated effluents, as the resin degradation is expected to
      contribute some organic carbon moieties misleading the actual performance of
      resin.

PMID- 23116828
TI  - Prognostic and predictive factors in colorectal cancer.
AB  - Colorectal cancer (CRC) is an important public health problem; it is a leading
      cause of cancer mortality in the industrialized world, second to lung cancer:
      each year there are nearly one million new cases of CRC diagnosed worldwide and
      half a million deaths (1). This review aims to summarise the most important
      currently available markers for CRC that provide prognostic or predictive
      information. Amongst others, it covers serum markers such as CEA and CA19-9,
      markers expressed by tumour tissues, such as thymidylate synthase, and also the
      expression/loss of expression of certain oncogenes and tumour suppressor genes
      such as K-ras and p53. The prognostic value of genomic instability, angiogenesis
      and proliferative indices, such as the apoptotic index, are discussed. The advent
      of new therapies created the pathway for a personalized approach of the patient.
      This will take into consideration the complex genetic mechanisms involved in
      tumorigenesis, besides the classical clinical and pathological stagings. The
      growing number of therapeutic agents and known molecular targets in oncology lead
      to a compulsory study of the clinical use of biomarkers with role in improving
      response and survival, as well as in reducing toxicity and establishing economic
      stability. The potential predictive and prognostic biomarkers which have arisen
      from the study of the genetic basis of colorectal cancer and their therapeutical
      significance are discussed.

PMID- 23116829
TI  - The advantages of retropancreatic vascular dissection for pancreatic head cancer
      with portal/superior mesenteric vein invasion: posterior approach pancreatico
      duodenectomy technique and the mesopancreas theory.
AB  - BACKROUNDS/AIMS: Surgery remains the single hope for long-term survival long-term
      survival in pancreatic head carcinoma. Portal vein invasion is no longer a
      contraindication for resection but could be technically challenging. The aim of
      the present study is to emphasize the advantages of the posterior approach in
      duodenopancreatectomy with portal vein resection. METHODS: The present series
      includes 16 patients with duodenopancreatectomy and portal/superior mesenteric
      vein resection and reconstruction duodenopancreatectomy invading the venous axis,
      performed from 2004 to 2011, and representing one author's experience. RESULTS: A
      lateral resection with direct suture was performed in 10 patients and the length
      of the resected venous wall was less than 1.2 cm. A segmental resection was
      performed in six patients and the length of resected vein did not exceed 3 cm
      (range, 1.5 - 3 cm). All venous resection extremities were cancer-free at final
      pathological report. Eleven patients were considered as R0 resection while 5
      patients were assessed as R1 at final pathological examination. Postoperative
      morbidity consisted of: 3 patients with postoperative pancreatic fistulae (grade
      A - 2 patients; grade C - 1 patient, requiring second look laparotomy for peri
      pancreatic abscesses) and 5 patients with delayed gastric emptying grade B.
      CONCLUSION: Portal/superior mesenteric vein resection during
      duodenopancreatectomy is safe and it is facilitated by the posterior approach.
      Moreover, the posterior approach facilitates total mesopancreas excision during
      duodenopancreatectomy for pancreatic head cancer, a technical feature that
      appears to be associated with an increased rate of negative resection margins.

PMID- 23116830
TI  - Gallstone disease in young population: incidence, complications, therapeutic
      approach.
AB  - OBJECTIVE: The purpose of this study is to highlight the high incidence of
      gallstones and the etiology in young people, as well as the fact that the onset
      is associated with complications: i.e. acute pancreatitis, jaundice. MATERIAL AND
      METHODS: This retrospective study was conducted between January 2007 and February
      2012 on patients admitted to the two surgical wards of Pitesti District Hospital
      and was based on the analysis of observation charts and theatre records. A total
      of 1905 cholecystectomies were performed, 1023 laparoscopic and 882 classic,
      respectively. RESULTS: A total of 36 patients aged between 16 and 25 years were
      included in the study. Laparoscopic cholecystectomy was performed in 34 patients,
      only two patients being operated by the classical open approach. 6 patients
      developed postoperative jaundice, which resolved under medical treatment in 3
      patients within 3-5 days. The remaining 3 patients underwent endoscopic
      retrograde cholangiopancreatography (ERCP) 4-5 days postoperatively. CONCLUSIONS:
      The most important risk factors for gallstones are: age, female gender, pregnancy
      and obesity. Common complications of gallstones in young people are: duct stones
      and acute pancreatitis.

PMID- 23116831
TI  - Molecular factors and criteria for predicting the response to neoadjuvant
      treatment in patients with esophageal squamous cell carcinoma (ESCC) --
      responder/non-responder.
AB  - Regarding the mortality causes, esophageal squamous cell carcinoma (ESCC) is on
      the 7th place in the US and the 6th place in the world, with 5 year overall
      survival rate of 14%, which is still modest in comparison to other digestive
      neoplasia. Multiples strategies were involved to improve this percentage,
      associating surgical procedures and chemo- and radio- oncologic therapies. The
      distant results showed sensitive improvement, after introduction of multimodality
      neoadjuvant therapies. MATERIAL AND METHOD: Fifty-seven patients diagnosed with
      ESCC were evaluated between 2006 and 2010, male preponderance (77%), average age
      of 55. A multimodality therapeutic protocol was used: first - radio-chemotherapy
      (RCT), second - surgery and/or third - chemo- or radiotherapy. Four weeks post
      RCT all patients were evaluated to determine the response to neoadjuvant
      treatment followed by surgery - esophageal resection. Histopathological (HP) and
      immunohistochemical (IHC) analysis of the pathological specimens were performed
      in order to identify the molecular predictors with responsive or non responsive
      character; the studied markers were p53 (Dako 1:50), Ki-67 (Biogenex, 1:20), c
      erbB-2 (Dako, 1:250). Based on these results, the working model used to determine
      the response to neoadjuvant therapy was tumor regression grade (TRG). RESULTS:
      After HP and IHC examination, the patients were included in two groups:
      responders and non responders (tumor cells > 10%). Complete neoplasia
      sterilization was achieved in 5 of the patients. CONCLUSIONS: We are able to
      state that the identification of potential predictive markers along with HP and
      IHC results represents a great perspective alternative in the ESCC therapy
      outcome. The detection of molecular type aggressiveness of the neoplastic process
      allows therapeutic orientation or guidance to certain therapy sequences or even
      to specific molecular targeted treatments.

PMID- 23116832
TI  - Hepatic trauma management in polytraumatised patients.
AB  - The specialty literature of the last decade presents the nonoperative management
      of the closed abdominal trauma as the treatment of choice. The purpose of this
      study is to highlight the importance of the optimal management of hepatic lesions
      considering the clinical, paraclinical and therapeutic approach. Our study is
      based on the analysis of the clinical and paraclinical data and also on the
      evaluation of the treatment results in 1671 patients with abdominal trauma
      affecting multiple organs who were treated at the Clinic of Surgery, County
      Hospital of Oradea from 2008 to 2011. The non-operative approach of the hepatic
      trauma, applied in 52% of the patients, was indicated in stable hemodynamic
      status, non-bleeding hepatic lesions on the abdominal CT, and the absence of
      other significant abdominal lesions. The remaining 48% were treated surgically.
      The postoperative evolution was free of complications in 72% of the patients
      while the rest of 28% presented one or more postoperative complications.
      ABBREVIATIONS: CT = Computer Tomography; ISS= Injury Severity Score; AIS =
      Abbreviated Index of Severity; AAST = American Association for the Surgery of
      Trauma; ARDS = Adult Respiratory Distress Syndrome.

PMID- 23116833
TI  - Primary anastomosis vs Hartmann procedure in acute complicated diverticulitis.
      Evolution over the last twenty years.
AB  - BACKGROUND/AIMS: Aim of this review is to assess the role and indications for
      primary sigmoidectomy with direct anastomosis for diverticulitis comparing it
      with the Hartmann's procedures. METHODS: A literature search was performed using
      MEDLINE (PubMed), Google Scholar and The Cochrane Library and the articles from
      January 1990 until June 2011 were analyzed. All patients were divided into three
      groups: primary anastomosis (PA), primary anastomosis and stoma protection (SP)
      and Hartmann's procedure (HP). Number of patients, overall mortality and
      morbidity, the rate of fistulization, the rate of reversal after SP (RSP) and
      after HP (RHP) and the Hinchey classification have been considered. RESULTS: The
      mortality was of 38/1010 patients (3.8%) for PA, 11/153 patients (7.2%) for SP
      and 139/800 patients (17.4%) for HP. The morbidity was reported in 103/325
      patients (31.7%) in PA, in 23/97 patients (23.7%) in SP and in 290/586 patients
      (49.5%) in HP. Fistula formation was recorded in 35/625 patients (5.6%) for PA,
      in 10/149 patients (16.4%) for RSP and 11/426 patients (6.4%) for RHP. The
      intestinal continuity was restored in 82/628 patients (56.9%) who underwent SP
      and in 315/581 patients (54.2%) undergoing HP. A total of 790 patients (54.5%)
      were classified in class I-II Hinchey and total of 659 patients (45.5%) was
      classified in class III-IV Hinchey. CONCLUSION: The PA has a lower morbidity and
      mortality in relation to the HP and except some limited indications, should be
      used as treatment of choice in the case of diverticulitis.

PMID- 23116835
TI  - Extraperitoneal mobilization of the omentum--analysis of a personal series of 12
      patients.
AB  - OBJECTIVE: The aim of the paper is to evaluate the results achieved after
      mobilization of the omentum outside the peritoneal cavity. MATERIAL AND METHOD:
      Between 01.01.2006-01.01.2012, the main author has performed an extraperitoneal
      mobilization of the omentum in 12 patients. The indications for the use of this
      flap were: prophylactic filling of the remnant space after the Miles procedure -
      4 cases, solving of some pelvisubperitoneal and perineal complications after
      rectal surgery - 3 cases, covering of vascular prosthesis - 3 cases (2 of them
      with active infection) and closure of a post-pneumonectomy bronchial fistula - 1
      case. The mobilization of the flap was performed by laparotomy - 10 cases, by
      laparoscopy - 1 case and transdiaphragmatic (thoracotomy) - 1 case; all the
      procedures were performed by the same team, with no assistance on behalf of a
      plastic surgeon. RESULTS: We have encountered one immediate postoperative death
      through myocardial infarction on postoperative day 12 (vascular prosthesis
      infection in a 75 years old patient). Based on the clinical and imagistic
      evaluation, we have encountered no necrosis of the omental flap. At late follow
      up (1-5 years) we have encountered no significant complications related to the
      use of this flap. CONCLUSIONS: The omentum is a solution for a great variety of
      defects located outside the peritoneal cavity; it's mobilization is relatively
      simple and does not involve a major morbidity. Knowledge of the omentum's anatomy
      and techniques of mobilization are mandatory in digestive, thoracic and vascular
      surgery.

PMID- 23116834
TI  - Modern therapeutic approach of acute severe forms of pancratitis. A review of the
      literature and experience of Surgical Department No III Cluj.
AB  - The title of "the great abdominal drama" attributed to acute pancreatitis is
      fully justified by the impressive clinical presentation, the deep consumptive
      character of physio-pathological processes taking place, the severity of the
      complications and the complexity of the treatment. MATERIALS AND METHODS: The aim
      of our study was to analyze the results on a number of 81 consecutive patients
      hospitalized in the Surgical Clinic III Cluj during 28 months, all diagnosed with
      severe forms of acute pancreatitis. There were two groups of patients, non
      surgical (43 cases) and surgical cases (38 cases), respectively. The diagnosis
      and forms of the disease took into account the clinical picture, serum amylase,
      CPR and Balthazar procalcitonine,together with the classification of the lesions
      on CT scan. RESULTS: All patients were admitted to the intensive care unit and
      received supportive treatment such as antibiotics, pancreatic exocrine secretion
      inhibitors and proton pump inhibitors. The surgical act in the 38 cases was
      indicated by septic intra-abdominal pressure or high functionality threatening
      vital viscera. Intraoperatively the abscesses were drained, the necrotic areas
      were removed and cholecystectomy was performed in patients with biliary etiology.
      Statistically, we obtained significant differences in the incidence of
      complications between the group of patients operated and those not operated (p =
      0.000048), but not in what concerns the length of hospitalization (p = 0.99999)
      and the number of deaths (p = 0.2102). The overall mortality was 14.41%,
      comparable to that found in the literature. In none of the patients CT guided
      drainage of collections was performed prior to surgery, which was a major
      drawback of the treatment. CONCLUSIONS: Our results support the importance of an
      early diagnosis and medical treatment, the delayed surgery being required in high
      intra-abdominal pressure or SEPS.

PMID- 23116836
TI  - Breast-conserving surgery in breast cancer.
AB  - The breast cancer treatment is based nowadays on new surgical options: breast
      conserving surgery, which applies at least for the first and second stage cancer,
      with radical intention. We have been practicing breast-conserving surgery for the
      last 16 years and we have performed 303 breast conserving operations from a total
      of 673. We recorded 12 local recurrences (3,96%) and 2 deaths due to cancer
      progression. Our protocol includes removal of the primary tumor with enough
      surrounding tissue to ensure negative margins of the resectable specimen,
      associated with axillary lymph-node dissection and postoperative breast
      irradiation. Our oncologist indicated chemotherapy on different postoperative
      conditions: tumor size, axillary lymph node involvement, patient's age, etc. The
      purpose of this paper is to emphasize our modest experience, nevertheless to draw
      the attention on important results, obtained by long-term monitoring of the
      patients who underwent breast-conserving surgery, in a two prospective protocols,
      and demonstrate the importance and applicability of breast conserving therapy.
      The conclusion of this study is that breast-conserving surgery followed by breast
      irradiation is reliable, as the results are similar with radical mastectomies;
      the main objective is to obtain a good cosmetic result, which depends on tumor
      size / breast size.

PMID- 23116837
TI  - Advanced anal squamous cell carcinoma -- radiotherapy or surgery?
AB  - BACKGROUND: Anal and rectal cancers occupy the third position of death causes in
      Poland. Adenocarcinoma is the most frequent among the tumours in this group.
      Squamous cell carcinoma can be relatively less common. This kind of carcinoma may
      rather affect the anus than the rectum. Although the lesion is perceived as not
      very malignant and as such responsive to radiant energy therapy, some cases may
      require surgical treatment. METHODS: Within 1999-2008 (the observation period of
      10 years) there were 18 patients treated for anal squamous cell carcinoma at the
      Department of Thoracic Surgery, General and Oncological Surgery of the Medical
      University of Lodz, at the Surgical Department of the Ministry of Interior and
      Administration Hospital in Lodz and at the Teleradiotherapy Department of Mikolaj
      Kopernik Voivodship Specialist Hospital in Lodz. Each patient underwent
      radiochemotherapy with Mitomycin and 5-Fluorouracil and Lucovorin. The applied
      radiation doses ranged between 45-54 Gy in eighteen 2.0 Gy fractions. The
      abdomino-perineal resection of the rectum (APR) was performed in 3 patients
      (16.5%) who did not show full regression of the carcinoma. In all three cases the
      histopathological diagnosis preceded the surgical procedure. RESULTS: For the
      total number of 18 patients with anal squamous cell carcinoma the mean
      observation period was 5.5 years, in the group of the operated patients the mean
      survival rate was 48 months (the median of 14-74 months) while for the group of
      the patients treated conservatively the mean survival rate amounted to 55 months
      (the median of 17-82 months, p=0.23). The mean 5-year disease-free survival rate
      was rather similar to the same rate of the general group, whereas the post
      operative complications occurred in 66% of surgical procedures and 27% of
      teleradiotherapeutic procedures. CONCLUSIONS: Combined radiotherapy and
      chemotherapy can be the method of choice in treating anal squamous cell
      carcinoma. Surgery should be used in advanced cases, when complete regression on
      radiochemotherapy cannot be observed. The abdomino-perineal resection of the
      rectum is the kind of a procedure that may be accompanied with a vast number of
      complications. Nevertheless, it still remains a necessary therapeutic method in
      the described cases.

PMID- 23116838
TI  - Microsurgery for the aneurysms of the basilar artery apex.
AB  - The aneurysms of the Basilar Artery apex (ABA) are not very common. My personal
      experience derives from having performed surgery on a number of 3340 patients
      with cerebral aneurysms at the Department of Vascular Neurosurgery II in
      Bucharest between 1979 and 2010. In 234 (7%) of the aneurysms they were located
      in the posterior vasculature. In 146 patients, representing 4.37% of the total
      number of patients with cerebral aneurysms and 62.39% of those with aneurysms of
      posterior vasculature, the location was in the basilar artery apex. The mean age
      of the 146 patients with aneurysms of the basilar artery apex (ABA) was 45.2
      years, varying between 34 and 71 years old. Most cases (69 -47.26%) were in the
      41-50 years age group. Aneurysms were found in 68 males (46.57%) and 78 females
      (53.42%) suggesting a slight predominance in female patients. The main reason for
      hospitalization was subarachnoid haemorrhage. There were four reports of patients
      having three episodes of subarachnoid bleeding in the three months preceding the
      surgery. The mean time between the last subarachnoid bleeding and the hospital
      admission was 26 days, ranging between 1 and 62 days. On admission three patients
      were in a severe general and neurological state (Hunt IV and V, respectively).
      The diagnostic assessment for those patients started with computer tomography
      (CT) followed by brain angiogram for the four main vessels. The main challenges
      for the surgical treatment of such lesions are due to the complex vascular
      anatomy of the basilar artery apex, to the direct vicinity of these aneurysms
      with the base of the skull and with vital neural structures in the
      interpeduncular fossa as well as due to difficulties in gaining proximal control
      over them. The post-surgical evolution was excellent and good in 131 (89.72%) of
      patients, unsatisfactory in 8 patients (5.48%), while 8 patients (5.48%) died.
      Three of the 8 patients marked by an unsatisfactory evolution presented with
      right-side hemiballismus and paresis of the 3rd cranial nerve, while other three
      remained in a vegetative state. Post-operative hydrocephaly was reported in 10
      patients (6.8%).

PMID- 23116839
TI  - Nasopharyngeal carcinoma -- analysis of risk factors and immunological markers.
AB  - PURPOSE: To analyze the risk factors associated with Nasopharyngeal Carcinoma
      (NPC)in patients admitted to the ENT Department at Coltea Clinical Hospital in
      order to assess the similarities and differences as compared to the
      epidemiological data internationally reported. PATIENTS AND METHODS: This is a
      retrospective study on 178 cases that met the inclusion criteria from 2003 to
      2011. RESULTS AND DISCUSSIONS: There are a number of specific characteristics
      noticed in our study group: a larger number of cases aged over 60 than younger
      patients; a linear fall in number of the cases aged between 30-39 years;
      approximately one third of the cases did not have any of the traditional risk
      factors; more than 10% of the cases were associated with lymphoma, etc.
      CONCLUSIONS: The immunologic pattern of our patients presenting undifferentiated
      NPC is the following: MNF116, CK19, S100, CD34betaE12, Ki67, EBV positive. The
      rest of the markers were negative (CerB2, EGFR, COX2, p53, CK7, CD117, VGFR,
      PCNA, L26/CD20, UHCL1, CD15, CD30, VIM, TTF1, CLA, CK17, CEA, LMP, CD79a, EMA).

PMID- 23116841
TI  - Jejunal diverticula causing massive intestinal bleeding.
AB  - Small bowel diverticula are rare formations and some are prone to complications
      such as lower gastrointestinal bleeding. We report the case of a patient with
      hemorrhagic shock following upper gastrointestinal bleeding. A 39-year-old
      patient was admitted to the unit for recurrent bleeding. The patient received
      transfusions and selective arteriography was performed which reported bleeding at
      the level of the ileocolic artery. Laparatomy was performed and blood was found
      at the entire colon and small intestine up to 40 cm of Treitz angle where
      multiple diverticula were visualized. Bowel resection was performed. Although
      duodeno-jejunal diverticula are rare, a special attention should be paid to this
      clinical entity as it can be a cause of recurrent upper gastrointestinal
      bleeding.

PMID- 23116840
TI  - True and false incomplete duplications of the common bile duct and their impact
      on therapy.
AB  - The congenital anomalies of the common bile duct (CBD) represent a real challenge
      for the surgeon, and not recognizing them may have two consequences: either
      generate incomplete or incorrect surgical solutions, or, even worse, lead to
      iatrogenic pathology. The association between the anomalies of the CBD and
      biliary lithiasis, biliary cancer or other hepatobiliopancreatic pathology may
      lead to a pre/perioperative diagnosis; frequently, the incertitude persists. We
      present 2 cases: one with an incomplete duplication of the CBD and the other with
      a false duplication. We wish to underline the sovereign value of cholangio-MRI
      with 3 D reconstructions in the diagnosis and description of the anatomy of the
      biliary ducts, superior, in some cases, to the intraoperative cholangiography or
      ERCP.

PMID- 23116842
TI  - A primary hydatid cyst in the abdominal wall -- case report.
AB  - INTRODUCTION: A solitary primary hydatid cyst in the abdominal wall is an
      exceptional entity, even in countries where the Echinococcus infection has a high
      rate, being considered an endemic disease. CASE PRESENTATION: We report a case of
      a 70-year-old Caucasian man who presented to our clinic with a slow-growing
      painless parietal mass in the abdominal wall, right flank area. The diagnosis of
      cystic mass was established at the ultrasound exam. There were no findings that
      could describe a hydatic cyst. The punction at the surgical intervention revealed
      a "clear, stone liquid like"; due to the high risk of major injury of the
      abdominal wall, we performed partial resection of the outer cystic wall,
      proligerous membrane removal and drainage. The patient had an uneventful post
      operative recovery. The histopathology confirmed the suspected diagnosis.
      CONCLUSION: Hydatid cyst should be considered in the differential diagnosis of
      every abdominal intraparietal cystic mass, especially in regions where the
      disease is endemic. The best treatment is the total excision of the cyst
      preserving an intact wall (complete cystectomy). Otherwise, removing the
      proligerous membrane with partial pericyst's resection (partial pericystectomy)
      and drainage should be considered.

PMID- 23116843
TI  - Rare urogenital malformation associated with complex vascular malformation --
      case report.
AB  - BACKGROUND: Class 3 urogenital malformations are a rarely encountered in the
      clinical setting. The association with complex vascular malformations represent a
      challenge in diagnosis and intraoperative management with an enhanced degree of
      the complexity. CASE PRESENTATION: Young female presented to the emergency
      department with pain in the left lower quadrant and unspecific abdominal symptoms
      that appear regularly one week prior and during her menstruation. Diagnostic
      studies and intraoperative findings lead to the diagnosis of a rare urogenital
      malformation associated with complex vascular malformations. In conclusion the
      most helpful diagnostic study was the abdominal MRI. Regarding the functional
      status of the postoperative urogenital tract no clear assessment can be made yet.

PMID- 23116844
TI  - Arthroplasty risk after kidney or liver transplant.
AB  - In recent years the rate of kidney or liver transplantation has increased
      considerably, with an increasing rate of immunosuppressant medication for
      secondary bone disorders. As the rate of organ transplantation increases, the
      greater predisposition of these patients to hip or knee arthroplasty is noticed.
      Although arthroplasty is safe in the general population, its safety in liver
      transplant recipients is unclear. The purpose of this study is to evaluate safety
      and durability of hip or knee arthroplasties in liver or kidney transplanted
      patients. Our study included 5 hip and knee arthroplasties performed in
      transplanted liver and kidney. All patients underwent immunosuppressive therapy.
      All cases were submitted to postoperative antibiotic therapy and in the case of
      cemented implants, antibiotic impregnated cement was used. There were no major
      short-term or long-term complications. We noticed no case of postoperative
      sepsis, and implant durability has not been affected by the directly transplant
      related causes. In conclusion arthroplasty for patients with kidney or liver
      transplant has a positive impact on their quality of life, being a safe and
      successful procedure with minimum perioperative safeguards.

PMID- 23116845
TI  - Splenic sarcoidosis -- a case report.
AB  - Patient aged 66 years, was admitted for splenomegaly grade III/IV, haematological
      hypersplenism and medium / large secondary anemia, diagnosed in the hematology
      clinic, where a myeloproliferative syndrome was denied. Was performed
      splenectomy, splenic lodge toilet and drainage. Histopathology was established
      the diagnosis of splenic sarcoidosis. Good postoperative evolution. Main issues
      discussed are etiopathogeny, diagnostic and therapeutic, that this rare disease
      of unknown etiology is giving.

PMID- 23116846
TI  - Prehospital trauma care: a clinical review.
AB  - INTRODUCTION: There are many controversies related to the trauma patient care
      during the pre-hospital period nowadays. Due to the heterogeneity of the rescue
      personnel and variability of protocols used in various countries, the benefit of
      the prehospital advanced life support on morbidity and mortality has been not
      established. METHOD: Systematic review of the literature using computer search of
      the Library of Medicine and the National Institutes of Health International
      PubMed Medline database using Entre interface.We reviewed the literature in what
      concerns the basic and advanced life support given to the trauma patients during
      the prehospital period. RESULTS: Although the organization of the medical
      emergency system varies from a country to another, the level of patient'scare can
      be classified into two main categories: Basic Life Support (BLS) and Advanced
      Life Support (ALS).There are many studies addressing what to be done at the
      scene.The prehospital care can be divided into two extremes: stay and play/treat
      then transfer or scoop and run/load and go. CONCLUSIONS: A balance between "scoop
      and run" and "stay and play" is probably the best approach for trauma patients.
      The chosen approach should be made according to the mechanism of injury (blunt
      versus penetrating trauma), distance to the trauma center (urban versus rural)
      and the available resources.

PMID- 23116848
TI  - 7 T versus 3T contrast-enhanced breast magnetic resonance imaging of invasive
      ductulolobular carcinoma: first clinical experience.
AB  - PURPOSE: Here we describe our first experience with contrast-enhanced (CE) MRI of
      breast cancer at 7 tesla (T), compared to 3T and histopathology. MATERIALS AND
      METHODS: A 52 year old female patient with a mammographically suspicious breast
      mass (BI-RADS V) underwent 7 T CE-MRI. Results were described according to the BI
      RADS-MRI criteria and compared to 3T and histopathology. RESULTS: After contrast
      administration, a homogeneously enhancing, irregular spiculated mass was depicted
      at both 3T and 7 T; sizes were identical. The most malignant kinetic curve was
      characterized by a rapid initial rise followed by a wash-out pattern in the
      delayed phase, i.e. a type 3 curve, at both field strengths. Even though T1
      effects of contrast agents are suggested to be reduced at higher fields,
      quantification of contrast enhancement-to-noise ratio showed a ratio of 4.6 at 7
      T and 2.8 at 3T when comparing contrast-to-noise of the mass before and after
      contrast administration. Both examinations, using a single dose of gadolinium
      based contrast agent, achieved good image quality. Final histopathological
      evaluation showed an invasive ductulolobular carcinoma with an intraductal
      component. CONCLUSION: This initial experience suggests that clinical contrast
      enhanced 7 T MRI of the breast is technically feasible and may allow BI-RADS
      conform analysis.

PMID- 23116847
TI  - Beneficial effect of genistein on lowering blood pressure and kidney toxicity in
      fructose-fed hypertensive rats.
AB  - The study evaluates the effects of genistein on blood pressure (BP) and
      ultrastructural changes in kidney of fructose-fed hypertensive rats. Male Wistar
      rats were fed a diet containing 60 % starch or 60 % fructose as the source of
      carbohydrate. After 15 d, rats in each dietary group were divided into two groups
      and were treated with either genistein (1 mg/kg per d) in dimethylsulfoxide
      (DMSO) or 30 % DMSO alone. BP, pressor mechanisms, protein kinase C-betaII (PKC
      betaII) expression, endothelial NO synthase (eNOS) expression and renal
      ultrastructural changes were evaluated after 60 d. Fructose-fed rats displayed
      significant elevation in BP and heart rate. Significant increase in plasma
      angiotensin-converting enzyme (ACE) activity, alterations in renal lipid profile,
      nitrite and kallikrein activity, enhanced expression of membrane-associated PKC
      betaII and decreased expression of eNOS were observed in them. Histology and
      electron microscopic studies showed structural changes in the kidney. Genistein
      administration lowered BP, restored ACE, PKC-betaII and eNOS expression and
      preserved renal ultrastructural integrity. These findings demonstrate that
      genistein has effects on eNOS activity in renal cells, leading to eNOS activation
      and NO synthesis. These effects could have been mediated by activation of PKC
      betaII. The observed benefits of genistein make it a promising candidate for
      therapy of diabetic kidney disease.

PMID- 23116849
TI  - Thermal stability of superhydrophobic, nanostructured surfaces.
AB  - The thermal stability of superhydrophobic, nanostructured surfaces after thermal
      annealing was explored. Flat surfaces coated with hydrophobic diamond-like carbon
      (DLC) via plasma polymerization of hexamethyldisiloxane (HMDSO) showed a gradual
      decrease in the water contact angle from 90(o) to 60(o) while nanostructured
      surfaces maintained superhydrophobicity with more than 150 degrees  for annealing
      temperatures between 25 and 300 degrees C. It was also found that surfaces with
      nanostructures having an aspect ratio of more than 5.2 may maintain
      superhydrophobicity for annealing temperatures as high as 350 degrees C; above
      this temperature, however, the hydrophobicity on surfaces with lower aspect ratio
      nanostructures gradually degraded. It was observed that regardless of the aspect
      ratios of the nanostructure, all superhydrophobic surfaces became
      superhydrophilic after annealing at temperatures higher than 500 degrees C.

PMID- 23116850
TI  - Effect of surface site interactions on potentiometric titration of hematite
      (alpha-Fe2O3) crystal faces.
AB  - Time dependent potentiometric pH titrations were used to study the effect of
      atomic scale surface structure on the protonation behavior of the structurally
      well-defined hematite/electrolyte interfaces. Our recently proposed thermodynamic
      model [1,25] was applied to measured acidimetric and alkalimetric titration
      hysteresis loops, collected from highly organized (001), (012), and (113) crystal
      face terminations using pH equilibration times ranging from 15 to 30 min.
      Hysteresis loop areas indicate that (001) faces equilibrate faster than the (012)
      and (113) faces, consistent with the different expected ensembles of singly-,
      doubly-, and triply-coordinated surface sites on each face. Strongly non-linear
      hysteretic pH-potential relationships were found, with slopes exceeding
      Nernstian, collectively indicating that protonation and deprotonation is much
      more complex than embodied in present day surface complexation models. The
      asymmetrical shape of the acidimetric and alkalimetric titration branches were
      used to illustrate a proposed steric "leaky screen" repulsion/trapping
      interaction mechanism that stems from high affinity singly-coordinated sites
      electrostatically and sterically screening lower affinity doubly- and triply
      coordinated sites. Our data indicate that site interaction is the dominant
      phenomenon defining surface potential accumulation behavior on single crystal
      faces of metal oxide minerals.

PMID- 23116851
TI  - Nanoparticle-stabilized carbon dioxide-in-water foams with fine texture.
AB  - The concept of hydrophilic/CO(2)-philic balance (HCB) was extended to describe
      stabilization of carbon dioxide-in-water (C/W) foams (also called emulsions) with
      silica nanoparticles adsorbed at the CO(2)-water interface. Opaque, white C/W
      foams (bubble diameter <100 MUm) were generated with either PEG-coated silica or
      methylsilyl modified silica nanoparticles in a beadpack with CO(2) densities
      between 0.2 and 0.9 g mL(-1). For methylsilyl modified silica nanoparticles, 50%
      SiOH modification provided an optimal HCB for generation and stabilization of
      viscous C/W foams with high stability. The apparent viscosity measured with a
      capillary tube viscometer reached 120-fold that of a CO(2)-water mixture without
      nanoparticles, a consequence of the small bubble size and the energy required to
      deform a high density of aqueous lamellae between CO(2) bubbles. Air-in-water
      (A/W) foams stabilized with nanoparticles were used to gain insight into the
      relationship between nanoparticle surface properties and adsorption of the
      nanoparticles at various types of interfaces. With suitable nanoparticles, A/W
      foams were stable for at least 7 days and C/W foams were stable for at least 23
      h. The ability to achieve long term stability for nanoparticle stabilized C/W
      foams could offer an alternative to conventional surfactants, which are known to
      have much lower adsorption energies.

PMID- 23116852
TI  - Tuning thermoresponsive behavior of diblock copolymers and their gold core
      hybrids: part 1. Importance of placement of amphiphilic end groups on the diblock
      copolymers.
AB  - We report the effects of use and placement of amphiphilic end groups as a
      valuable tool to achieve significant changes in the thermoresponsive properties
      of diblock copolymers without the need to resort to compositional changes. We
      prepared diblock copolymers of di(ethylene glycol) methyl ether methacrylate and
      oligo(ethylene glycol) methyl ether acrylate with phenyl dithioester and
      carboxylic acid chain ends and compared the effects of placement of these
      amphiphilic chain ends on the cloud points of the copolymers. All the copolymers
      were high molecular weight (greater than 20 kDa) with a polydispersity between
      1.1 and 1.2, and the cloud points were measured by UV-vis spectrophotometry and
      reported as the temperature at 50% normalized transmission. The thermoresponse
      showed a significant dependency on end group placement, reaching as much as a 28
      degrees C difference in measured cloud point simply by exchanging end group
      placement rather than compositional changes. The effect is attributed to changes
      in the solvation and mobility from chain end placement affecting the degree of
      association of the chains. The underlying effect is due to the
      hydrophilic/hydrophobic balance in combination with the use of amphiphilic chain
      end placement that can be applied to copolymers with different blocks at the
      chain ends. This work shows that substantial changes in thermo-response
      properties can be achieved by re-arranging monomer components rather than
      changing monomer composition. This may have value in biomedical materials where
      the range of acceptable monomers is limited.

PMID- 23116853
TI  - Steric hindrance colloidal microsphere approach to fabricate ordered and
      interconnected Pt or Pt/Ag hollow hemispheres.
AB  - A steric hindrance colloidal microspheres approach (SHCMA) has been developed for
      the fabrication of ordered Pt or Pt/Ag nanoparticles composite interconnected
      hollow hemispheres via colloidal lithography and physical vapor deposition.
      Monolayer ordered silica or silica/Ag nanoparticles composite microspheres partly
      embedded into the polydimethylsiloxane (PDMS) were used as template, and Pt was
      sputtered on it. Due to the PDMS stamp functionalized as a steric hindrance
      substrate, which guaranteed that the ordered silica or silica/Ag nanoparticles
      composite microspheres were only coated with Pt film on the sides that exposed in
      air. After removing the template particles, large area ordered interconnected Pt
      or Pt/Ag nanoparticles composite hollow hemispheres were generated. The
      fabricated Pt hollow hemispheres have flat bottoms and are flexible and robust
      enough to be easily folded. In addition to successfully solving the challenge
      about ordered structure construction of the hollow Pt or Pt/Ag nanoparticles
      composite hemispheres here, we also could finely control the wall thickness of
      these hemispheres easily by changing the sputtering time or current.

PMID- 23116854
TI  - Effect of surface properties on the electrorheological response of
      hematite/silicone oil dispersions.
AB  - In this work we present an investigation of the influence of particle surface
      characteristics on the electrorheological (ER) behavior of suspensions of either
      pure or modified hematite (alpha-Fe(2)O(3)) particles dispersed in silicone oil.
      The modification consisted of either dehydration or hydrophobization of the
      particles before preparing the suspensions. A comparison was performed between
      the electrorheological responses of suspensions with the same volume fraction of
      hematite particles having different surface properties. The effects of applied
      electric field strength on the viscosity, yield stress and dynamic moduli of
      these suspensions were examined. It was found that the usual positive ER
      response, that is, enhanced values of the yield stress and elastic modulus
      induced by the electric field were obtained for hematite and, to a lesser extent,
      for dried hematite suspensions. In contrast, a "negative ER effect", i.e., the
      reduction of yield stress and elastic modulus upon application of electric field
      was observed for hydrophobically modified (oleic acid coated) hematite. This
      means that the field produces destruction of structures rather than their build
      up, above a threshold electric field strength.

PMID- 23116855
TI  - Electrolyte-induced precipitation of graphene oxide in its aqueous solution.
AB  - Graphene oxide (GO) can easily dissolve in water to form a stable homogeneous
      solution due to its hydrophilic property and ionization of functional groups.
      However, in this paper, it is reported that a strong electrolyte (HCl, LiOH,
      LiCl, LiBr, KCl, or KBr) can destabilize the GO solution, causing GO
      precipitation. This indicates that the electrostatic repulsion plays a critical
      role in stabilizing aqueous GO solution. The electrolyte-induced precipitates
      were characterized by transmission electron microscopy (TEM), Raman spectroscopy,
      and Fourier transform infrared spectroscopy (FTIR). The oxygen-containing
      functional groups of GO sheets, which are carboxyl, epoxy, and hydroxyl groups,
      remained unchanged during acid (HCl)- and salt (LiCl)-induced precipitations. In
      contrast, during the GO precipitation induced by a base (LiOH), the carboxyl
      group of GO sheets disappeared with a remarkable increase in hydroxyl group and
      aromatic C=C bonds. This indicates that the LiOH-induced GO precipitation
      resulted in the partial reduction of GO sheets. Furthermore, it was demonstrated
      that the HCl-induced GO precipitation is a feasible approach to deposit GO on a
      substrate as a Pt-free counter electrode for a dye-sensitized solar cell (DSSC),
      which exhibited 1.65% power conversion efficiency.

PMID- 23116856
TI  - Egon Matijevic, his personality and achievements.
AB  - This year's celebrity Egon Matijevic was born ninety years ago in the Croatian
      town of Otocac. He was educated in Croatia, where he started his extraordinary
      scientific career. After postdoctoral studies in England, Matijevic moved to the
      USA, where he joined Clarkson College of Technology (presently Clarkson
      University) in Potsdam, N.Y. Egon has stayed with Clarkson contributing
      significantly to the University, especially within the Department of Chemistry
      both in teaching and in research in the field of colloid chemistry. As a colloid
      chemist Egon was involved in examining physicochemical properties of colloids and
      interfaces, in several aspects of application and especially in the development
      of new methods for the preparation of well defined uniform particles. At present,
      his main focus lies in the application of colloidal systems in medicine. Egon
      Matijevic is a prominent scientist and his achievements have been recognized by
      the scientific community worldwide, being the recipient of numerous prestigious
      awards. The enthusiasm and spirit of Egon Matijevic is exceptional and we wish
      him to continue enjoying science and the art of living for many years to come.

PMID- 23116858
TI  - Preconcentration and determination of metal ions from fuel ethanol with a new
      2,2'-dipyridylamine bonded silica.
AB  - A silica surface chemically modified with [3-(2,2'-dipyridylamine) propyl] groups
      was prepared, characterized, and evaluated for its metal ion preconcentration in
      fuel ethanol. To our knowledge, we are the first authors who have reported the
      present modification on silica gel surface. The material was characterized using
      infrared spectra, scanning electronic microscopy, and (13)C and (29)Si solid
      state NMR spectra. Batch and column experiments were conducted to investigate for
      metal ion removal from fuel ethanol. The results showed that the Langmuir model
      describes the sorption equilibrium data of the metal ions in a satisfactory way.
      From the Langmuir isotherms, the following maximum adsorption capacities (in mmol
      g(-1)) were determined: 1.81 for Fe(III), 1.75 for Cr(III), 1.30 for Cu(II), 1.25
      for Co(II), 1.15 for Pb(II), 0.95 for Ni(II), and 0.87 for Zn(II). Thermodynamic
      functions, the change of free energy (DeltaG), enthalpy (DeltaH), and entropy
      (DeltaS) showed that the adsorption of metal ions onto Si-Pr-DPA was feasible,
      spontaneous, and endothermic. The sorption-desorption of the metal ions made
      possible the development of a preconcentration and quantification method of metal
      ions in fuel ethanol.

PMID- 23116857
TI  - A direct surface modification of iron oxide nanoparticles with various poly(amino
      acid)s for use as magnetic resonance probes.
AB  - Water soluble and biocompatible iron oxide nanoparticles coated with
      poly(aspartic acid) (PAsp), poly(asparagines) (PAsn), poly(2-hydroxy-ethyl L
      aspartamide) (PHEA), and poly-alpha,beta-(N-2-dimethylaminoethyl L-aspartamide)
      (PDMAEA) were prepared by hydrophobic interaction between hydrophobic iron oxide
      nanoparticles and each amphiphilic poly(amino acid)s graft polymer. The octadecyl
      side chain grafted poly(succinimide)(PSI-g-C(18)), used as a precursor polymer,
      was easily aminolyzed with nucleophilic compounds to form various poly(amino
      acid)s graft polymer (PAsp-g-C(18), PAsn-g-C(18), PHEA-g-C(18), PDMAEA-g-C(18),)
      and simultaneously stabilize the dispersion of iron oxide nanoparticles in
      aqueous solution. The diameters of the poly(amino acid)s coated iron oxide
      nanoparticles (PAIONs) were smaller than 30 nm in aqueous solution, extremely
      stable in aqueous solutions with a wide range of pH and salt concentrations.
      Further, all the PAIONs showed excellent MR signal intensities (high r(2) values)
      and the cellular uptake property of the PAIONs was also evaluated.

PMID- 23116859
TI  - Golf ball-like particles fabricated by nonsolvent/solvent-induced phase
      separation method.
AB  - Monodisperse poly(styrene-co-acrylic acid) (P(S-co-AA)) particles having a "golf
      ball-like" shape were prepared by nonsolvent/solvent-induced phase separation
      process. The method is simple and easy operation. The nonsolvent/solvent phase
      was mixture of butanol, n-heptane and toluene. The dimpled surface comes from the
      aggregation of oil droplets on the surface of polymer spheres. The dimple's
      morphology can be controlled by the polymer templates, dispersion medium,
      reaction time, and temperature. Reverse Pickering emulsion model was suggested
      for the formation of golf ball-like particles.

PMID- 23116860
TI  - Use of TX100-dangled epoxy as a reactive noncovalent dispersant of vapor-grown
      carbon nanofibers in an aqueous solution.
AB  - The dispersion of carbon nanotubes (CNTs) into individual particles or small
      bundles has remained a vexing problem that limits the use of the excellent
      properties of CNTs in composite applications. Noncovalent functionalization is an
      attractive option for changing the interfacial properties of nanotubes because it
      does not destroy the nanotube grapheme structure. In this study, a new reactive
      copolymer, epoxy-toluene diisocyanate-Triton X-100 (EP-TDI-TX100) was
      successfully synthesized, which is shown to be highly effective in dispersing
      vapor-grown carbon nanofibers (VGCNFs) into individual or small bundles, as
      evidenced by transmission electron microscopy (TEM) and UV-vis absorption
      spectra. The strong pi-pi interaction between VGCNFs and EP-TDI-TX100 was
      revealed by Raman spectra and the covalent reaction between curing agent was
      confirmed via Fourier transform infrared spectroscopy. For an effective
      dispersion, the optimum weight ratio of EP-TDI-TX100 to VGCNFs is 2:1. The
      maximum VGCNF concentration that can be homogeneously dispersed in an aqueous
      solution is approximately 0.64 mg/mL. The EP-TDI-TX100 molecules are adsorbed on
      the VGCNF surface and prevent reaggregation of VGCNFs, so that a colloidal
      stability of VGCNF dispersion can be maintained for 6 months.

PMID- 23116861
TI  - Charging and aggregation of negatively charged colloidal latex particles in the
      presence of multivalent oligoamine cations.
AB  - Charging and aggregation of negatively charged carboxyl latex particles in the
      presence of positively charged linear oligoamines containing 1-6 amine groups
      were investigated by electrophoretic mobility and dynamic light scattering. The
      oligoamines of low valence resemble simple inert salts and destabilize the
      suspensions by screening their charge. The oligoamines of higher valence induce
      overcharging at low concentrations, whereby destabilization is triggered by
      charge neutralization. At higher concentrations, destabilization is also induced
      by screening. The onset of first fast aggregation regime scales with the inverse
      six power of the valence in agreement with the Schulze-Hardy rule. The
      aggregation rates can be relatively well described by the DLVO theory which
      indicates that the interactions are governed by van der Waals and electrostatic
      double layer forces.

PMID- 23116862
TI  - Fabrication of vitamin E-enriched nanoemulsions: factors affecting particle size
      using spontaneous emulsification.
AB  - Oil-in-water nanoemulsions are finding increasing use as delivery systems to
      encapsulate lipophilic bioactive components in functional food, personal care,
      and pharmaceutical products. We have investigated the influence of system
      composition and preparation conditions on the particle size of vitamin E acetate
      (VE)-loaded nanoemulsions prepared by spontaneous emulsification. This method
      relies on the formation of very fine oil droplets when an oil/surfactant mixture
      is added to water. The oil-to-emulsion ratio content was kept constant (10 wt.%)
      while the surfactant-to-emulsion ratio (%SER) was varied (from 2.5 to 10 wt.%).
      Oil phase composition (vitamin E to medium chain triglyceride ratio) had a major
      effect on particle size, with the smallest droplets being formed at 8 wt.% VE and
      2 wt.% MCT. Surfactant type also had an appreciable impact on particle size, with
      TWEEN(r) 80 giving the smallest droplets from a group of food-grade non-ionic
      surfactants (TWEEN(r) 20, 40, 60, 80, and 85). Surfactant-to-emulsion ratio also
      had to be optimized to produce fine droplets, with the smallest droplets being
      formed at SER=10 wt.%. Particle size could also be reduced by increasing the
      temperature and stirring speed used when the oil/surfactant mixture was added to
      water. By optimizing system composition and homogenization conditions we were
      able to form VE-loaded nanoemulsions with small mean droplet diameters (d<50 nm)
      and low polydispersity indexes (PDI<0.13). The spontaneous emulsification method
      therefore has great potential for forming nanoemulsion-based delivery systems for
      food, personal care, and pharmaceutical applications.

PMID- 23116863
TI  - Letter to the editors.

PMID- 23116865
TI  - Unplanned kangaroo transport of a preterm infant.

PMID- 23116866
TI  - Sometimes a cigar is just a cigar.

PMID- 23116868
TI  - 2012 critical care transport workplace and salary survey.
AB  - Critical care transport (CCT) is provided in a unique and challenging out-of
      hospital environment. The workplace and salaries for CCT staff are similarly
      unique and distinct within the health care industry. An industry-specific
      workplace and salary survey was conducted under Federal Safe Harbor guidelines to
      update information for 2012. As safety is a key concern for CCT workers and
      organizations, the survey elicited industry best practices under safety
      management system (SMS) categories.

PMID- 23116869
TI  - Helicopter cabin design for emergency medical services and interhospital
      transfer.

PMID- 23116870
TI  - Large civilian air medical jets: implications for Australian disaster health.
AB  - Disasters involving multiple foreign nationals overseas will invariably
      necessitate an air medical response to repatriate the casualties to their
      respective home countries. Depending on the location of the incident and the
      number of casualties, foreign governments may need to perform a large-scale air
      medical response. This may involve using large civilian jet aircraft (LCJ) as an
      air medical platform. This paper provides a review of the current understanding
      when converting LCJs for air medical capability. This review concludes that LCJ
      configured for air medical capability can be used successfully in disasters. The
      findings indicate that standard civilian jets can be reconfigured for
      transporting multiple casualties. The use of these aircraft can be considered in
      disaster planning to complement existing military arrangements or as an
      alternative option. This strategy can be an inexpensive and effective option and
      should be considered by Australian disaster health agencies.

PMID- 23116871
TI  - Hemodynamics during an ambulance flight.
AB  - Transportation of patients may present challenges, especially if they need
      intensive care, require mechanical ventilation, or are hemodynamically unstable.
      In the reported case study, Picco-based measurements were used to track
      hemodynamic changes in a patient throughout the duration of a transfer, which
      included an air ambulance transport. If air medical transport is indicated,
      several additional physical and chemical considerations require awareness during
      the trip, planning, and pretransport patient preparation: first, that decreasing
      atmospheric pressure leads to reduced blood oxygenation, and second, that
      intracorporeal volume shifts may occur during takeoff and landing. To our
      knowledge, our findings represent the first measurements with a Picco system
      during interhospital patient transport that included an air medical flight.

PMID- 23116872
TI  - Helicopter emergency medical service inTehran, Iran: a descriptive study.
AB  - OBJECTIVE: The study provides descriptive information regarding missions
      performed by Tehran helicopter emergency medical services (HEMS) during a 1-year
      period. METHODS: All patients transferred by Tehran HEMS between March 2006 and
      March 2007 were enrolled in this descriptive study. Based on HEMS records,
      information was gathered on flight time, the number of patients transferred in
      each flight, and mission outcomes. RESULTS: During the 1-year study, a total of
      353 patients were transported via 138 helicopter flights to 4 medical care
      centers in Tehran. The mean flight time, the time from the initial call until the
      patient was delivered to a medical facility, was 36.56 +/- 18.44 minutes.
      CONCLUSION: Tehran HEMS is still far from attaining optimal values, particularly
      regarding flight time. More efforts are needed to improve the timing as a
      component of care and the quality of care provided by this system.

PMID- 23116873
TI  - HEMS in Slovenia: one country, four models, different quality outcomes.
AB  - OBJECTIVE: The objective of this study was to determine the quality of patient
      care using quality indicators in 4 different Slovenian helicopter emergency
      medical service (HEMS) models. METHODS: This was a cross-sectional study of all 4
      HEMS in Slovenia. We collected data on quality for the period from July 2003 to
      August 2008, in a sample of all eligible patients that were managed by HEMS
      during the study period (N = 833). We obtained the following data on emergency
      operations: the time and organizational features of the operation; the
      description of the patients' condition; and the on-site diagnostic and treatment
      procedures. We used the following as quality indicators: the number of
      resuscitated patients that were intubated; the number of patients with a Glasgow
      Coma Scale (GCS) score of # 8 that were intubated; the number of patients with
      acute coronary syndrome that received treatment with morphine, oxygen,
      nitroglycerine, and aspirin (MONA); the number of patients with a National
      Advisory Committee on Aeronautics (NACA) scale score of $ 4 with an intravenous
      line; the number of patients with a NACA score of $ 5 that were given oxygen; and
      the number of patients with a NACA score of $ 4 that were given appropriate
      analgesic treatment. RESULTS: Across all HEMS bases, 36 (87.8%) resuscitated
      patients were intubated; 122 (81.9%) patients with GCS # 8 were intubated; 149
      (89.2%) patients with ACS were given MONA treatment; 52 (92.9%) patients with a
      NACA score of $ 4 were given an intravenous line; 254 (92.7%) patients with a
      NACA score of $ 5 were given oxygen; and 18 (32.7%) trauma patients with a NACA
      score of $ 4 were given intravenous analgesics. The quality of patient management
      in HEMS in Slovenia is affected by the callout procedure, the presence or absence
      of a fixed rope, the type of helicopter operator, and the provider of the doctor
      in the helicopter team. CONCLUSIONS: The data from our study indicates that the
      quality of patient management in HEMS in Slovenia is high. It also seems that
      organizational factors play a role in the quality management of patients in HEMS
      as well, but their effect remains unclear and needs further evaluation.

PMID- 23116874
TI  - Latent epilepsy in pilots: two case reports.
AB  - Although epilepsy is rare in aviation personnel, 2 long-term duty pilots were
      discovered to have latent epilepsy. The first case presented is that of a 36-year
      old male pilot, with 16 years' flight time, and the second case describes a 30
      year-old male Black Hawk pilot with 11 years' duty time. Both reportedly
      experienced a sudden onset of tonic and clonic convulsions after they had been
      exposed to stressful conditions. Both of their clinical presentations were
      consistent with grand mal epilepsy, and their electroencephalogram (EEG) findings
      were consistent with epilepsy. Both were subsequently suspended from flying
      duties. An EEG has since been added as part of the pilot selection medical
      examination in the Royal Jordanian Air Force Medical Services.

PMID- 23116876
TI  - An exploratory study on STX6, MOBP, MAPT, and EIF2AK3 and late-onset Alzheimer's
      disease.
AB  - Both Alzheimer's disease (AD) and progressive supranuclear palsy (PSP) are a
      class of neurodegenerative diseases associated with the pathologic aggregation of
      tau protein in the human brain. They share some clinical and pathologic
      characteristics. A recent genome-wide association study reported several single
      nucleotide polymorphisms at the STX6, MOBP, MAPT, and EIF2AK3 in association with
      PSP. To explore whether these single-nucleotide polymorphisms are associated with
      AD risk, we conducted a case-control study to investigate the PSP-associated loci
      in 1592 Han Chinese subjects. Rs242557 at the MAPT locus was associated with late
      onset AD (LOAD) (odds ratio [OR], 1.175; p = 0.026), which appeared to be
      stronger for LOAD patients with apolipoprotein E (APOE) epsilon4 allele (OR,
      1.510), and this positive association was not changed after adjusting for age,
      sex, and the APOE epsilon4-carrier status (additive model: OR, 1.163; p = 0.036;
      dominant model: OR, 1.315; p = 0.010). Rs1768208 in MOBP and rs7571971 in EIF2AK3
      showed association only in the APOE epsilon4 positive subjects, and these did not
      appear to be independent of APOE. As for rs1411478 in STX6, we did not explore
      any association with LOAD. Our exploratory analysis mainly suggests an
      association of MAPT with LOAD, especially in APOE epsilon4 carriers. Genotypes at
      MOBP and EIF2AK3 confer risk predominantly in APOE epsilon4-positive subjects,
      with indications of an interaction between APOE and MOBP or EIF2AK3 on AD risk.

PMID- 23116877
TI  - In vivo glutamate measured with magnetic resonance spectroscopy: behavioral
      correlates in aging.
AB  - Altered availability of the brain biochemical glutamate might contribute to the
      neural mechanisms underlying age-related changes in cognitive and motor
      functions. To investigate the contribution of regional glutamate levels to
      behavior in the aging brain, we used an in vivo magnetic resonance spectroscopy
      protocol optimized for glutamate detection in 3 brain regions targeted by
      cortical glutamatergic efferents-striatum, cerebellum, and pons. Data from 61
      healthy men and women ranging in age from 20 to 86 years were used. Older age was
      associated with lower glutamate levels in the striatum, but not cerebellum or
      pons. Older age was also predictive of poorer performance on tests of visuomotor
      skills and balance. Low striatal glutamate levels were associated with high
      systolic blood pressure and worse performance on a complex visuomotor task, the
      Grooved Pegboard. These findings suggest that low brain glutamate levels are
      related to high blood pressure and that changes in brain glutamate levels might
      mediate the behavioral changes noted in normal aging.

PMID- 23116878
TI  - Parkinson disease is not associated with C9ORF72 repeat expansions.
AB  - Hexanucleotide expansions in the C9ORF72 gene are frequently found in patients
      with amyotrophic lateral sclerosis, frontotemporal dementia or both, some of whom
      exhibit concurrent extrapyramidal symptoms. To determine if repeat expansions are
      a cause of Parkinson's disease (PD), we used repeat-primed polymerase chain
      reaction to investigate the frequency of C9ORF72 repeat expansions in a cohort of
      478 patients with PD and 662 control subjects. Three control subjects were found
      to be expansion carriers, and no expansions were found among patients, suggesting
      that C9ORF72 expansions are not a common cause of PD.

PMID- 23116879
TI  - Preliminary study on the association of AQP4 promoter polymorphism with anti
      aquaporin-4 antibody positivity in southern Han Chinese patients with idiopathic
      demyelinating disorders of central nervous system.
AB  - OBJECTIVES: To identify the association of aquaporin-4 (AQP4) promoter
      polymorphism with the presence of anti-aquaporin-4 antibody (AQP4-Ab) in Southern
      Han Chinese patients with idiopathic demyelinating disorders of central nervous
      system. METHODS: Eighteen neuromyelitis optica (NMO), thirty-eight conventional
      MS (CMS), thirteen recurrent myelitis (RM), six recurrent optic neuritis (RON)
      patients and thirty-nine matched controls were enrolled. Polymorphisms of AQP4
      promoters 0 and 1 were determined by sequencing-based typing. RESULTS: Fourteen
      polymorphism loci were observed in AQP4-promoter 0, while the six ones were
      observed in AQP4-promoter 1. Among them, the frequency of polymorphism at
      position -1003bp (A-G) of AQP4-promoter 0 in AQP4-Ab-positive patients was
      significantly higher than that in AQP4-Ab-negative patients and controls (former:
      13/18 vs 20/45, P=0.046; latter: 13/18 vs 10/39, P=.001). The frequency of
      polymorphism at position between -401bp and -400bp (C inserted) of AQP4-promoter
      1 in AQP4-Ab-positive and -negative patients was significantly higher than that
      in controls (former: 5/16 vs 0/28, P=0.008; latter: 8/38 vs 0/28, P=0.027).
      CONCLUSIONS: Polymorphism at position -1003bp (A-G) of AQP4-promoter 0 is
      associated with the presence of anti-AQP4 antibody. Genetic variation in AQP4 may
      account for the susceptibility to AQP4-Ab-positive NMO and NMO spectrum disorders
      in Southern Han Chinese population.

PMID- 23116880
TI  - Resection of the epileptogenic lesion abolishes seizures and reduces inflammatory
      cytokines of patients with temporal lobe epilepsy.
AB  - Persistent neuroinflammation is implicated in the pathogenesis of seizures and
      neuronal degeneration of temporal lobe epilepsy (TLE). Circulating level of
      inflammatory cytokines was determined during inter-ictal period of 25 non
      operated and 10 patients (OP) submitted to anterior temporal lobectomy. OP
      patients showed marked reduction of IL-1beta, TNFalpha, MIP-1alpha, but not IL-6
      and TGF-beta1. Paired analysis done before and after lobectomy showed reduction
      of inflammatory cytokines but increased TGF-beta1 levels, and lack of seizures
      for more than 6 months. Maintenance of high TGF-beta1 and IL-6 cytokines in both
      groups suggests a role in down-regulation of neuroinflammation and promotion of
      brain tissue remodeling for neuronal reorganization.

PMID- 23116882
TI  - Community-acquired Clostridium difficile NAP1/027-associated diarrhea in an
      eighteen month old child.
AB  - Clostridium difficile infection (CDI), characterized by symptoms varying from
      diarrhea to life-threatening colitis, is a major complication of antibiotic
      therapy. Studies suggested that CDI is emerging as an important cause of
      childhood diarrhea in community and hospital settings. This work is the first
      report of a documented case of community-acquired CDI by a NAP1 hypervirulent
      strain in an eighteen month old child from Latin America.

PMID- 23116881
TI  - Efficacy and safety of sitagliptin added to ongoing metformin and pioglitazone
      combination therapy in a randomized, placebo-controlled, 26-week trial in
      patients with type 2 diabetes.
AB  - AIMS: To assess efficacy and safety of sitagliptin, a dipeptidyl peptidase-4
      inhibitor, in combination therapy with metformin (>=1500 mg/day) and pioglitazone
      (>=30 mg/day) in patients with type 2 diabetes (T2DM) with inadequate glycemic
      control (hemoglobin A1c [HbA1c] >=7.5% and <=11%). METHODS: This placebo
      controlled, double-blind study included 313 patients, mean baseline HbA1c=8.7%,
      who were randomized to receive sitagliptin 100 mg/day or placebo for 26 weeks.
      RESULTS: The addition of sitagliptin led to significant (P<.001) mean changes
      from baseline relative to placebo in HbA1c (-0.7%), fasting plasma glucose (-1.0
      mmol/L), and 2-h post-meal glucose (-2.2 mmol/L). In patients with baseline HbA1c
      >=9.0%, mean changes from baseline in HbA1c were -1.6% and -0.8% for the
      sitagliptin and placebo groups, respectively (between-group difference -0.8%;
      P<.001). The incidences of reported adverse events were generally similar between
      the treatment groups. Incidences of symptomatic hypoglycemia were 7/157 [4.5%]
      and 6/156 [3.8%] in the sitagliptin and placebo groups, respectively (P=.786).
      Two patients, both in the placebo group, experienced an episode of hypoglycemia
      that required non-medical assistance. CONCLUSIONS: In this 26-week study,
      addition of sitagliptin to combination therapy with metformin and pioglitazone
      improved glycemic control and was generally well tolerated.

PMID- 23116883
TI  - A 5-year follow-up study of brain cortical and subcortical abnormalities in a
      schizophrenia cohort.
AB  - BACKGROUND: Magnetic resonance imaging studies have demonstrated that patients
      with schizophrenia have thinner cortex in prefrontal and temporal brain regions,
      and enlarged lateral ventricles, compared to healthy subjects. Longitudinal
      studies have shown progressive brain tissue loss and ventricular dilatation among
      patients, predominantly in the early phase of the illness. Evidence for
      progression in more chronic phases of schizophrenia is less established. METHODS:
      Measurements of cortical thickness, cortical volume and subcortical volumes were
      obtained from 52 patients with long-term treated schizophrenia and 63 healthy
      subjects who were scanned twice over five years. Differences in brain
      measurements across time and group were investigated using general linear models.
      RESULTS: Compared to controls, patients had similar patterns of thinner cortex
      and smaller cortical volumes in prefrontal and temporal regions at both time
      points. In the follow-up interval regional cortical volumes decreased and lateral
      ventricle volumes increased in both groups. There was a trend level interaction
      effect of group and time for the right lateral ventricle, but not for cortical
      measurements. This effect was related to higher degree of negative symptoms at
      follow-up. CONCLUSIONS: Regional differences in cortical thickness and volume
      between long-term treated patients with schizophrenia and healthy subjects are
      stable across five years, while right lateral ventricle volumes tend to increase
      more in the patients. The findings indicate that brain structure abnormalities
      found in schizophrenia are not progressive in the chronic stage of the disease,
      but that some progression in subcortical structures may be present in patients
      with poor outcome.

PMID- 23116884
TI  - How specific are emotional deficits? A comparison of empathic abilities in
      schizophrenia, bipolar and depressed patients.
AB  - Empathy is a rather elaborated human ability and several recent studies highlight
      significant impairments in patients suffering from psychiatric disorders, such as
      schizophrenia, bipolar disorder or major depression. Therefore, the present study
      aimed at comparing behavioral empathy performance in schizophrenia, bipolar and
      depressed patients with healthy controls. All subjects performed three tasks
      tapping the core components of empathy: emotion recognition, emotional
      perspective taking and affective responsiveness. Groups were matched for age,
      gender, and verbal intelligence. Data analysis revealed three main findings:
      First, schizophrenia patients showed the strongest impairment in empathic
      performance followed by bipolar patients while depressed patients performed
      similar to controls in most tasks, except for affective responsiveness. Second, a
      significant association between clinical characteristics and empathy performance
      was only apparent in depression, indicating worse affective responsiveness with
      stronger symptom severity and longer duration of illness. Third, self-report data
      indicate that particularly bipolar patients describe themselves as less empathic,
      reporting less empathic concern and less perspective taking. Taken together, this
      study constitutes the first approach to directly compare specificity of empathic
      deficits in severe psychiatric disorders. Our results suggest disorder-specific
      impairments in emotional competencies that enable better characterization of the
      patient groups investigated and indicate different psychotherapeutic
      interventions.

PMID- 23116886
TI  - Synthesis, antioxidant and antimicrobial activity of novel vanillin derived
      piperidin-4-one oxime esters: preponderant role of the phenyl ester substituents
      on the piperidin-4-one oxime core.
AB  - The study has been achieved the efficient synthesis of vanillin derived piperidin
      4-one oxime esters (5a-m) via four step reaction involved Mannich reaction of
      vanillin, acetone and ammonium acetate to obtain 2,6-bis(4-hydroxy-3
      methoxyphenyl)-piperidin-4-one 2 followed by N-methylation and oximation.
      Further, to enhance the biological activity of vanillin derived piperidin-4-one
      oxime core, esterification of 4 with substituted benzoyl chlorides in the
      presence of strong organic base t-BuOK accomplished a series of vanillin derived
      piperidin-4-one oxime esters (5a-m). The synthesized analogues are screened for
      their antioxidant and antimicrobial studies and the preponderant effect of the
      phenyl ester substituents on the biological activity of piperidin-4-one oxime
      core was demonstrated. Among the tested compounds, 5i and 5j are emerged as
      outperformed antioxidants than standard Butylated hydroxy anisole (BHA) whereas,
      compounds 5b and 5d manifested potent antibacterial and antifungal activity than
      standard streptomycin and fluconazole respectively.

PMID- 23116887
TI  - Synthesis and antimycobacterial activity of calpinactam derivatives.
AB  - Synthesis of calpinactam 1, a fungal antimycobacterial metabolite, utilizing
      solid-phase peptide synthesis is described. To explore the structure-activity
      relationships of 1, its derivatives with different amino acids were also
      synthesized on the basis of the same synthetic strategy. These derivatives were
      examined for antimycobacterial activity against Mycobacterium smegmatis. Among
      them, only peptide 6d having d-Ala in place of d-Glu showed moderate activity.

PMID- 23116885
TI  - The presentation of dermatoglyphic abnormalities in schizophrenia: a meta
      analytic review.
AB  - Within a neurodevelopmental model of schizophrenia, prenatal developmental
      deviations are implicated as early signs of increased risk for future illness.
      External markers of central nervous system maldevelopment may provide information
      regarding the nature and timing of prenatal disruptions among individuals with
      schizophrenia. One such marker is dermatoglyphic abnormalities (DAs) or unusual
      epidermal ridge patterns. Studies targeting DAs as a potential sign of early
      developmental disruption have yielded mixed results with regard to the strength
      of the association between DAs and schizophrenia. The current study aimed to
      resolve these inconsistencies by conducting a meta-analysis examining the six
      most commonly cited dermatoglyphic features among individuals with diagnoses of
      schizophrenia. Twenty-two studies published between 1968 and 2012 were included.
      Results indicated significant but small effects for total finger ridge count and
      total A-B ridge count, with lower counts among individuals with schizophrenia
      relative to controls. Other DAs examined in the current meta-analysis did not
      yield significant effects. Total finger ridge count and total A-B ridge count
      appear to yield the most reliable dermatoglyphic differences between individuals
      with and without schizophrenia.

PMID- 23116888
TI  - Design and synthesis of 2-aminothiazole based antimicrobials targeting MRSA.
AB  - Privileged structure-based libraries have been shown to provide high affinity
      lead compounds for a variety of important biological targets. The present study
      describes the synthesis and screening of a 2-aminothiazole based compound library
      to determine their utility as antimicrobials, focusing on MRSA. Several of the
      compounds in this series demonstrated improved antimicrobial activity as compared
      to ceftriaxone (CTX), a beta-lactam antibiotic. The most potent compound (21) had
      MICs in the range of 2-4 MUg/ml across a panel of Staphylococcus aureus strains.
      In addition, trifluoromethoxy substituted aminothiazoles and aminobenzothiazoles
      were found to be potent antimicrobials with MICs of 2-16 MUg/ml.

PMID- 23116889
TI  - Discovery and evolution of phenoxypiperidine hydroxyamide dual CCR3/H1
      antagonists. Part II: optimising in vivo clearance.
AB  - The second part of this communication focuses on the resolution of issues
      surrounding the series of hydroxyamide phenoxypiperidine CCR3/H(1) dual
      antagonists described in Part I. This involved further structural exploration
      directed at reducing metabolism and leading to the identification of compound 60
      with a greatly improved in vivo pharmacokinetic profile.

PMID- 23116890
TI  - Synthesis and evaluation of 3-123I-iodo-5-[2-(S)-3-pyrrolinylmethoxy]-pyridine
      (niodene) as a potential nicotinic alpha4beta2 receptor imaging agent.
AB  - Nicotinic acetylcholine receptors (nAChRs) are downregulated in disease
      conditions such as Alzheimer's and substance abuse. Presently, (123)I-5-IA-85380
      is used in human studies and requires over 6h of scanning time, thus increases
      patient discomfort. We have designed and synthesized 3-iodo-5-[2-(S)-3
      pyrrolinylmethoxy]pyridine (niodene) with the aim to have faster binding kinetics
      compared to (123)I-5-IA-85380, which may reduce scanning time and help in imaging
      studies. Binding affinity K(i) of niodene for rat brain alpha4beta2 receptors in
      brain homogenate assays using (3)H-cytisine was 0.27 nM. Niodene, 10nM displaced
      >95% of (18)F-nifene bound to alpha4beta2 receptors in rat brain slices. By using
      the iododestannylation method, (123)I-niodene was obtained in high radiochemical
      purity (>95%) but with low radiochemical yield (<5%) and low specific activity
      (~100 Ci/mmol). Autoradiograms show (123)I-niodene localized in the thalamus and
      cortex, which was displaced by nicotine (thalamus to cerebellum ratio=4; cortex
      to cerebellum ratio=1.6). Methods of radioiodination need to be further evaluated
      in order to obtain (123)I-niodene in higher radiochemical yields and higher
      specific activity of this potentially useful new SPECT imaging agent.

PMID- 23116891
TI  - Synthesis of new opioid derivatives with a propellane skeleton and their
      pharmacologies: part 3, novel propellane derivatives with pentacyclic skeletons.
AB  - Previously reported propellane derivative KNT-42 preferred the kappa receptor and
      functioned as a message part in the message-address concept, but its affinity for
      the kappa receptor was not high. To improve affinity, we synthesized five
      pentacyclic propellane derivatives designed for the purpose of fixing the
      conformation of KNT-42. The etheno- and ethano-bridged derivatives SYK-347 and
      SYK-393 exhibited high affinity and selectivity for the kappa receptor, whereas
      the other derivatives did not. These results would be due to the different ranges
      of movement of the basic nitrogens and less basicity of the nitrogens due to the
      electron withdrawing effect of the introduced hydroxy or keto group. SYK-347 and
      SYK-393 preferring the kappa receptor were expected to be useful for designing
      selective ligands for opioid receptor types, especially the kappa receptor.

PMID- 23116892
TI  - Structural modifications of a 3-methoxy-2-aminopyridine compound to reduce
      potential for mutagenicity and time-dependent drug-drug interaction.
AB  - (S)-1-((4-(3-(6-Amino-5-methoxypyridin-3-yl)-1-isopropyl-1H-pyrazol-4
      yl)pyrimidin-2-yl)amino)propan-2-ol, 1, was recently identified as a potent
      inhibitor of the oncogenic kinase bRAF. Compounds containing 3-methoxy-2
      aminopyridine, as in 1, comprised a promising lead series because of their high
      ligand efficiency and excellent ADME profile. However, following metabolic
      oxidation, compounds in this series also demonstrated two significant safety
      risks: mutagenic potential and time-dependent drug-drug interaction (TDI).
      Metabolite identification studies revealed formation of a reactive metabolite. We
      hypothesized that minimizing or blocking the formation of such a metabolite would
      mitigate the safety liabilities. Our investigation demonstrated that structural
      modifications which either reduced the electron density of the 3-methoxy-2
      aminopyridine ring or blocked the reactive site following metabolic oxidation
      were successful in reducing TDI and AMES mutagenicity.

PMID- 23116893
TI  - Matrix metalloproteinase-1 mitral expression and -1607 1G/2G gene promoter
      polymorphism in mitral chordae tendinae rupture.
AB  - Understanding the pathogenesis of mitral chordae tendinae rupture (MCTR) is
      essential for identification of risk factors. Mitral matrix metalloproteinase
      (MMP) triggers the signal cascade that instigates cardiac fibrosis, which may be
      a predisposing factor in MCTR. We investigated associations among MMP1
      expression, MMP1 -1607 1G/2G polymorphism and mitral chordae tendinae rupture
      (MCTR). This study enrolled 185 patients (group A) receiving mitral valve
      replacement. Group A included 65 patients with MCTR and 120 controls without
      MCTR. MMP1 was assessed on a semiquantitative scale (0-3) by immunohistochemical
      staining. For genetic association study, another 227 subjects were recruited for
      group B, including 75 with MCTR and 152 controls. The gene polymorphisms were
      analyzed by polymerase chain reaction. In group A, MCTR patients had a higher
      MMP1 expression compared to controls (P < 0.001). Binary regression analysis
      showed the variation in the MCTR patients was independently explained by MMP1 (P
      = 0.027). Hypertension and MMP1 staining had a synergistic effect on the MCTR
      occurrence (P < 0.001). In group B, MMP1 -1607 1G allele was increased in
      patients with MCTR compared to controls (P = 0.014). The odds ratio for the 1G/1G
      genotype to the 2G/2G genotype was 3.22 (P = 0.009). Univariate and logistic
      regression analysis showed an independent association between MCTR and MMP1 -1607
      1G/2G polymorphism (P = 0.028 and 0.032, respectively). Since MMP1 mitral
      expression and -1607 1G/2G polymorphism were associated with MCTR independently
      of other baseline characteristics, MMP1 may play a role in the individual
      susceptibility to MCTR.

PMID- 23116894
TI  - Involvement of caspase-12-dependent apoptotic pathway in ionic radiocontrast
      urografin-induced renal tubular cell injury.
AB  - Contrast medium (CM) induces a direct toxic effect on renal tubular cells. This
      toxic effect subjects in the disorder of CM-induced nephropathy. Our previous
      work has demonstrated that CM shows to activate the endoplasmic reticulum (ER)
      related adaptive unfolding protein response (UPR) activators. Glucose-regulated
      protein 78 (GRP78)/eukaryotic initiation factor 2alpha (eIF2alpha)-related
      pathways play a protective role during the urografin (an ionic CM)-induced renal
      tubular injury. However, the involvement of ER stress-related apoptotic signals
      in the urografin-induced renal tubular cell injury remains unclear. Here, we
      examined by the in vivo and in vitro experiments to explore whether ER stress
      regulated pro-apoptotic activators participate in urografin-induced renal injury.
      Urografin induced renal tubular dilation, tubular cells detachment, and necrosis
      in the kidneys of rats. The tubular apoptosis, ER stress-related pro-apoptotic
      transcriptional factors, and kidney injury marker-1 (kim-1) were also
      conspicuously up-regulated in urografin-treated rats. Furthermore, treatment of
      normal rat kidney (NRK)-52E tubular cells with urografin augmented the
      expressions of activating transcription factor-6 (ATF-6), C/EBP homologous
      protein (CHOP), Bax, caspase-12, JNK, and inositol-requiring enzyme (IRE) 1
      signals. Urografin-induced renal tubular cell apoptosis was not reversed by the
      inhibitors of ATF-6, JNK signals or CHOP siRNA transfection, but it could be
      partially reversed by the inhibitor of caspase-12. Taken together, the present
      results and our previous findings suggest that exposure of CM/urografin activates
      the ER stress-regulated survival- and apoptosis-related signaling pathways in
      renal tubular cells. Caspase-12-dependent apoptotic pathway may be partially
      involved in the urografin-induced nephropathy.

PMID- 23116895
TI  - The superior mesenteric artery syndrome: a rare etiology for proximal obstructive
      syndrome.

PMID- 23116896
TI  - (1)H NMR spectroscopy for the in vitro understanding of the glycaemic index.
AB  - The glycaemic index (GI) characterises foods by using the incremental area under
      the glycaemic response curve relative to the same amount of oral glucose. Its
      ability to differentiate between curves of different shapes, the peak response
      and other aspects of the glycaemic response is contentious. The present pilot
      study aimed to explore the possibility of using 1H NMR spectroscopy to better
      understand in vivo digestion characteristics as reflected in the glycaemic
      response of carbohydrate-rich foods; such an approach might be an adjunct to the
      in vivo GI test. The glycaemic response of two types of raw wheat flour (2005
      from Griffith NSW, Chara, Row 10, Plot 6:181 and store-bought Colese Plain Flour)
      and a cooked store-bought flour was tested and compared with results recorded
      during the in vitro enzymatic digestion of the wheat flour samples by
      glucoamylase from Aspergillus niger (EC 3.2.1.3) as monitored by 1H NMR
      spectroscopy. Comparing the digestion time courses of raw and cooked wheat starch
      recorded in vitro strongly suggests that the initial rate of glucose release in
      vitro correlates with the glycaemic spike in vivo. During the in vitro time
      courses, approximately four times as much glucose was released from cooked starch
      samples than from raw starch samples in 90 min. Monitoring enzymatic digestion of
      heterogeneous mixtures (food) by 1H NMR spectroscopy showcases the effectiveness
      of the technique in measuring glucose release and its potential use as the basis
      of an in vitro method for a better understanding of the GI.

PMID- 23116897
TI  - An immunostimulating water insoluble beta-glucan of an edible hybrid mushroom:
      isolation and characterization.
AB  - An immunostimulating water-insoluble beta-glucan isolated from hot alkaline
      extract of the fruiting bodies of an edible somatic hybrid mushroom of Pleurotus
      florida and Calocybe indica var. APK2 showed significant macrophage, splenocyte,
      and thymocyte activations. On the basis of total hydrolysis, methylation
      analysis, and NMR experiments ((1)H, (13)C, DQF-COSY, TOCSY, NOESY, DEPT-135, and
      HSQC), the repeating unit of the polysaccharide is established.

PMID- 23116898
TI  - Serum proteinogram, acute phase proteins and immunoglobulins in dogs
      experimentally infected with Rangelia vitalii.
AB  - The present study aimed to evaluate the serum proteinogram, acute phase proteins
      (APPs) and immunoglobulins (Igs) of dogs experimentally infected by Rangelia
      vitalii in the acute phases of the disease. Banked serum samples collected on
      days 0, 10 and 20 during a previously reported R. vitalii experimental infection
      were used to analyze the serum proteinogram, APPs (C-reactive protein - CRP and
      alpha-1-acid glycoprotein - AGP) and Igs (IgM, IgG, IgA and IgE) in the current
      study. Total protein and albumin level were significantly (P<0.05) decreased at
      day 10 PI and 20 PI in infected sera compared to the control sera. Alpha-1
      globulin (day 10 PI) and gamma globulin (day 20 PI) were increased (P<0.01) in
      infected sera. Alpha-2 globulin (days 10 and 20 PI) and beta-2 globulin (day 10
      PI) were decreased (P<0.05) in infected sera compared to control sera. Beta-1
      globulin fraction did not differ statistically between sera. Serum CRP and AGP
      concentrations were significantly increased (P<0.05) at days 10 and 20 PI in
      infected sera. IgG was increased at days 10 (P<0.05) and 20 PI (P<0.01) in
      infected sera. Furthermore, it was also observed an increase (P<0.01) in the
      levels of IgM, IgA, and IgE in infected sera than control sera. We conclude that
      R. vitalii infection causes alterations in the proteinogram, and increases in the
      levels of APPs and Igs. Further studies are essentials to define the causes of
      these pathological changes in this disease.

PMID- 23116899
TI  - PCR-RFLP genotyping of Toxoplasma gondii from chickens from Espirito Santo state,
      Southeast region, Brazil: new genotypes and a new SAG3 marker allele.
AB  - Brazil is one of the regions with the highest prevalences of Toxoplasma gondii in
      humans and animals. Because free-range chickens become infected by feeding from
      ground contaminated with oocysts, the prevalence of T. gondii in this host has
      been widely used as an indicator of the strains prevalent in the environment. The
      genetic variability among T. gondii isolates from different healthy and sick
      hosts all over the world has been recently studied. Three clonal genetic lineages
      (Types I, II and III) were initially recognised as predominant in Western Europe
      and the United States. T. gondii strains are genetically diverse in South
      America. In Brazil, recombination plays an important role in strain
      diversification. The objective of this study was to genetically characterise T.
      gondii isolates from free-range chickens from Espirito Santo state, Southeast
      region, Brazil, using polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP). A total of 44 isolates among 47 previously described
      isolates (TgCkBr234-281) from free-range chickens were included in this study.
      Strain typing was performed using 12 PCR-RFLP markers: SAG1, SAG2, alt. SAG2,
      SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, Apico and CS3. Eleven genotypes were
      identified. Ten isolates (23%) were grouped into four novel genotypes. Four
      isolates, distributed in four counties, corresponded to the Type BrI lineage, the
      genotype found most frequently in Brazil. No clonal Types I, II or III lineages
      were found. Two novel genotypes were represented by single isolates. Unique
      alleles were identified for the markers SAG1, c22-8 and CS3, and for the first
      time, a unique allele was found for the marker SAG3. Although a large number of
      T. gondii genotypes have already been identified from a variety of animal hosts
      in Brazil, new genotypes are continuously identified from different animal
      species. This study confirmed the diversity of T. gondii in Brazil and
      demonstrates clonal Type I, II and III lineages are rare in this country.

PMID- 23116900
TI  - [Update on idiopathic pulmonary fibrosis. Introduction].

PMID- 23116901
TI  - [Alveolar epithelial cell injury as an etiopathogenic factor in pulmonary
      fibrosis].
AB  - Idiopathic pulmonary fibrosis (IPF) is characterized by a progressive
      accumulation of extracellular matrix and an imbalance between profibrotic and
      antifibrotic mediators. In the last few years, understanding of the mechanisms of
      the biology of IPF has increased. One of the most significant discoveries is the
      finding that alveolar epithelial cell injury plays an important role in the
      pathogenesis of this disease. In this review, we describe some of the mechanisms
      involved in alveolar cell injury and their contribution to the development of
      IPF.

PMID- 23116903
TI  - [Future prospects in the treatment of idiopathic pulmonary fibrosis].
AB  - After the three revisions done by Cochrane for the last ten years, it has been
      demonstrated that most of the clinical assays performed with corticosteroids,
      immunomodulators and antifibrotic drugs have shown inconclusive results for the
      treatment of idiopathic pulmonary fibrosis. To date, only pirfenidone has proved
      to have significant efficacy in controlled clinical trials in the treatment of
      this disease. At present, a large number of new drugs are being tested, which
      offers a new perspective in some ways optimistic concerning the future treatment
      of this disease.

PMID- 23116902
TI  - [From exclusion to uncertainty: the route to diagnosing idiopathic pulmonary
      fibrosis].
AB  - Idiopathic pulmonary fibrosis (IPF) is a differentiated disease within the
      idiophatic interstitial pneumonias. IPF is progressive and fibrosing and is
      limited to the lungs. This entity generally affects persons older than 50 years
      old and is associated with the radiological and/or histological pattern of usual
      interstitial pneumonia (UIP). Clinically, IPF causes progressive exertional
      dyspnea and nonproductive cough. In most patients, physical examination reveals
      fine bibasilar inspiratory crackles and 50% of patients have digital clubbing.
      There are no specific laboratory alterations. Bronchoalveolar lavage and
      transbronchial biopsy will not establish the diagnosis of IPF but are useful to
      exclude other entities. Definitive diagnosis requires: a) exclusion of other,
      defined clinical entities or diffuse pulmonary diseases of known cause, and b)
      the presence of a histological pattern of UIP on analysis of pulmonary tissue
      from surgical biopsy, radiological evidence of the defined pattern of UIP on high
      resolution computed tomography, or both.

PMID- 23116904
TI  - Impact of susceptibility profiles of Gram-negative bacteria before and after the
      introduction of ertapenem at a medical center in northern Taiwan from 2004 to
      2010.
AB  - This retrospective observational study evaluated the impact of antimicrobial
      consumption on antimicrobial susceptibility among aerobic Gram-negative bacteria
      after introducing ertapenem to the formulary of a teaching hospital (1130 beds)
      in northern Taiwan. Data on consumption of various antimicrobial agents,
      expressed as defined daily dose/1000 patient-days (DDD/1000 PD), were collected
      retrospectively from hospital pharmacy records 2 years before and 5 years after
      the introduction of ertapenem (October 2005). During the study period, the
      consumption of ampicillin and aminoglycosides decreased significantly. In
      contrast, the consumption of cefoxitin, ceftazidime, cefpirome, piperacillin
      tazobactam, carbapenems (ertapenem, imipenem, and meropenem), and
      fluoroquinolones (ciprofloxacin, levofloxacin, and moxifloxacin) increased
      significantly over time. There was a significant increase in the rate of
      susceptibility of Escherichia coli to ampicillin, cefotaxime, ceftazidime,
      piperacillin-tazobactam, cefpirome, amikacin, and levofloxacin; an increase in
      the rate of susceptibility of Klebsiella pneumoniae to ceftazidime, cefepime,
      cefpirome, piperacillin-tazobactam, meropenem, levofloxacin, and amikacin; a
      significant decrease in the rate of susceptibility of Pseudomonas aeruginosa to
      meropenem; and a significant decrease in the rate of susceptibility of
      Acinetobacter baumannii to ceftazidime, carbapenems, ciprofloxacin, and
      levofloxacin. The rate of antibiotic susceptibility to ertapenem of extended
      spectrum beta-lactamase producers, including E. coli and K. pneumoniae, remained
      stable. Usage of ertapenem was found to be negatively and significantly
      associated with the susceptibility rates of P. aeruginosa to meropenem and
      gentamicin. Significantly negative correlations were noted between the use of
      ertapenem and the rates of susceptibility of A. baumannii to ceftazidime,
      piperacillin-tazobactam, carbapenems (imipenem and meropenem), ciprofloxacin, and
      levofloxacin.

PMID- 23116905
TI  - Chirp-evoked otoacoustic emissions in children.
AB  - OBJECTIVE: The purpose of the study was to investigate the properties of
      otoacoustic emissions (OAEs) evoked by chirp stimuli and compare them with
      standard click-evoked OAEs. Differences between evoked OAEs in children with and
      without spontaneous otoacoustic emissions (SOAEs) were also assessed. METHODS:
      OAEs were first recorded from 54 children (age 4-10 years) in a screening setup.
      In each ear five OAE measurements were made using two types of chirps (7.5 ms and
      10.5 ms) at around 70 dB pSPL; clicks at 70 and 80 dB pSPL; and a standard
      synchronized SOAE stimulation protocol. Tympanometry was also conducted.
      Pass/refer criteria based on signal to noise ratios (SNRs) were applied to all
      OAEs. Pass/refer rates from all methods (OAEs evoked by chirps and clicks, and
      tympanometry) were compared. Additionally, half-octave-band values of OAE SNRs
      and response levels were used to assess statistical differences. RESULTS: Chirp
      evoked OAEs generated a similar number of passes to click-evoked OAEs when the
      same level of stimulus was used. When using lower stimulus levels, both chirp-
      and click-evoked OAEs diagnosed nearly all ears that failed tympanometry. The
      response levels and SNRs of OAEs evoked by clicks and chirps were very similar.
      The highest response levels were in the 1.4 kHz half-octave band. The SNRs for
      ears with SOAEs were highest at 1.4 kHz, whereas they were at 4 kHz for ears
      without SOAEs. Both response levels and SNRs were higher by about 5 dB for ears
      with SOAEs than ears without SOAEs. Also all ears with SOAEs generated a pass
      result in screening, while ears without SOAEs gave a pass less frequently (at
      least 30% fewer cases). CONCLUSIONS: The results suggest that performance of
      chirp-evoked OAEs for screening purposes is similar to click-evoked OAEs when the
      same stimulus level is applied. OAEs evoked with lower stimulus levels (70 vs. 80
      dB pSPL) are more sensitive to middle ear pathology. The presence of SOAEs
      significantly influences the pass rates of OAEs evoked by chirps and clicks.

PMID- 23116906
TI  - Speech outcome after early repair of cleft soft palate using Furlow technique.
AB  - OBJECTIVE: The earlier closure of palatal cleft is the better the speech outcome
      and the less compensatory articulation errors, however dissection on the hard
      palate may interfere with facial growth. In Furlow palatoplasty, dissection on
      the hard palate is not needed and surgery is usually limited to the soft palate,
      so the technique has no deleterious effect on the facial growth. The aim of this
      study was to assess the efficacy of Furlow palatoplasty technique on the speech
      of young infants with cleft soft palate. METHODS: Twenty-one infants with cleft
      soft palate were included in this study, their ages ranged from 3 to 6 months.
      Their clefts were repaired using Furlow technique. The patients were followed up
      for at least 4 years; at the end of the follow up period they were subjected to
      flexible nasopharyngoscopy to assess the velopharyngeal closure and speech
      analysis using auditory perceptual assessment. RESULTS: Eighteen cases (85.7%)
      showed complete velopharyngeal closure, 1 case (4.8%) showed borderline
      competence, and 2 cases (9.5%) showed borderline incompetence. Normal resonance
      has been attained in 18 patients (85.7%), and mild hypernasality in 3 patients
      (14.3%), no patients demonstrated nasal emission of air. Speech therapy was
      beneficial for cases with residual hypernasality; no cases needed secondary
      corrective surgery. CONCLUSION: Furlow palatoplasty at a younger age has
      favorable speech outcome with no detectable morbidity.

PMID- 23116907
TI  - [Upper gastrointestinal bleeding as the first manifestation of lung cancer].

PMID- 23116908
TI  - Vaccination: a victim of its own success.

PMID- 23116909
TI  - The HPV vaccine and parental consent.

PMID- 23116910
TI  - Writing an excuse or educating the patient.

PMID- 23116911
TI  - Treating children whose parents refuse to have them vaccinated.

PMID- 23116912
TI  - Residents' role in immunizing adults: rationale, opportunity, obstacles, and
      strategies.

PMID- 23116914
TI  - The National Childhood Vaccine Injury Act and the supreme court's interpretation.

PMID- 23116915
TI  - Should participation in vaccine clinical trials be mandated?

PMID- 23116916
TI  - The HPV vaccine controversy.

PMID- 23116917
TI  - New media, old messages: themes in the history of vaccine hesitancy and refusal.

PMID- 23116918
TI  - Closing immunization gaps in the U.S: how a little collusion could go a long way.

PMID- 23116919
TI  - An ethical take on the "stress vaccine".

PMID- 23116921
TI  - Assessing patient satisfaction with community pharmacy in the UAE using a newly
      validated tool.
AB  - BACKGROUND: Patient satisfaction has become an integral component of the quality
      of healthcare services. It has been used for the purpose of performance
      assessment, reimbursement, and quality management of health service delivery. It
      has been suggested that patient satisfaction could be a predictor of health
      related behavior. OBJECTIVES: To develop and validate a tool for use within the
      Arabic context to assess patient satisfaction. To assess patient satisfaction
      with current community pharmacy services in the UAE using the validated tool.
      METHODS: A systematic process was used to develop an assessment tool that could
      be used within the Arabic context and establish its validity and reliability.
      Survey participants assessed their satisfaction with the services based on a 5
      point Likert-type scale: Poor = 1, Fair = 2, Good = 3, Very good = 4, Excellent =
      5. The anonymous questionnaire was distributed over a 5-month period to eligible
      participants in public places such as malls and shopping markets, in various
      emirates across the UAE. Those who were 21 years or older, taking at least one
      scheduled (regular) medication and having adequate Arabic or English language
      proficiency were included. RESULTS: The instrument comprised four dimensions:
      Information, Relationship, Accessibility and Availability. Participants required
      more information about medications and self-management (Mean = 2.49 +/- 1.19).
      Measures of competence, i.e., care, interest, time, confidence and trust, could
      also be improved (Mean = 3.05 +/- 1.07). Accessibility scores measuring physical,
      geographical and financial items were lowest (Mean = 2.80 +/- 1.33). Overall
      scores on availability of medications indicated relative satisfaction with this
      dimension (Mean = 3.51 +/- 0.7). CONCLUSIONS: This study is the first to use a
      patient satisfaction tool specifically developed for the Arabic context. Patient
      satisfaction scores in all dimensions were significantly lower than published
      data, suggesting patients have unmet expectations of community pharmacy services
      in the UAE. Stakeholders could utilize this information to help in the design and
      delivery of improved services that could lead to increased demand.

PMID- 23116922
TI  - On the staining of human tissue-cultured (Chang) conjunctival cells with rose
      bengal and lissamine green.
AB  - PURPOSE: To assess the staining of Chang conjunctival epithelial cells with rose
      bengal and lissamine green. METHODS: A human (Chang) conjunctival epithelial cell
      line was grown on plastic plates in 10% foetal calf serum-supplemented medium in
      5% carbon dioxide-air at 37 degrees C. Cells were examined daily between days 2
      and 10 of culture, reaching confluence after 7 days, for overall appearance
      before and after exposure for 3 min at 37 degrees C to solutions of either rose
      bengal or lissamine green (dissolved in saline, PBS or balanced salts solution).
      Measurements of nucleus and cell size were made on some confluent cultures.
      RESULTS: Chang cells, regardless of the growth state or the vehicle used, stain
      very intensely with rose bengal, with the nucleus of the cells showing the most
      notable dye uptake. Cultures showing such intensive staining with rose bengal
      were consistently non-staining with lissamine green. Nucleus size, based on
      measurements of the long dimension (NUCLONG) were the same for rose bengal or
      lissamine green exposed cells (averaging 19.5+/-2.4 MUm and 18.8+/-2.9 MUm,
      respectively). Cell size at confluence, based on measurements of the long
      dimension of lissamine green-exposed cells (LONG), averaged 40.5+/-7.2 MUm. The
      cytoplasm-to-nucleus ratio (based on LONG-NUCLONG/NUCLONG) averaged 1.177+/-0.406
      (i.e. approximately a 1:1 ratio). CONCLUSIONS: Cultured Chang conjunctival cells
      stain intensely with rose bengal, but the same is not seen with lissamine green.
      The cell morphology is indicative of flattened epithelial cells.

PMID- 23116923
TI  - Daily disposable lenses: the better alternative.
AB  - As the literature has described the increasing penetration of DDSL into the
      contact lens market worldwide, this review aimed to describe the development of
      this modality as a solution to the problems experienced with other types of
      contact lenses. The advantages of DDSL in comparison to reusable lenses are
      discussed. The important role of the practitioner in prescribing for and managing
      patients using this lens type are also examined, in particular with respect to
      non-compliance. Problems with the use of this lens type and possible solutions
      are explored and new applications and future development in this field are
      described.

PMID- 23116925
TI  - Info/information theory: speakers choose shorter words in predictive contexts.
AB  - A major open question in natural language research is the role of communicative
      efficiency in the origin and on-line processing of language structures. Here, we
      use word pairs like chimp/chimpanzee, which differ in length but have nearly
      identical meanings, to investigate the communicative properties of lexical
      systems and the communicative pressures on language users.If language is designed
      to be information-theoretically optimal, then shorter words should convey less
      information than their longer counterparts, when controlling for meaning.
      Consistent with this prediction, a corpus analysis revealed that the short form
      of our meaning-matched pairs occurs in more predictive contexts than the longer
      form. Second, a behavioral study showed that language users choose the short form
      more often in predictive contexts, suggesting that tendencies to be information
      theoretically efficient manifest in explicit behavioral choices. Our findings,
      which demonstrate the prominent role of communicative efficiency in the structure
      of the lexicon, complement and extend the results of Piantadosi, Tily, and Gibson
      (2011), who showed that word length is better correlated with Shannon information
      content than with frequency. Crucially, we show that this effect arises at least
      in part from active speaker choice.

PMID- 23116926
TI  - Polymerization efficiency through translucent and opaque fiber posts and bonding
      to root dentin.
AB  - PURPOSE: To investigate the polymerization efficiency through translucent and
      opaque glass fiber posts and the bond strength of a self-adhesive resin to root
      dentin. METHODS: Translucent and opaque silanated conical posts, identical in
      length, diameter and shape (n=8), were cemented to incisor bovine roots using
      RelyX Unicem Clicker. Photoactivation was performed only through the posts. The
      roots were transversally sectioned (cervical, middle and apical thirds) and the
      push-out test was carried out. Data were analyzed using two-way ANOVA and
      Fisher's LSD method (5%). Failure modes were classified under magnification. An
      elastomer mold of a bovine incisor root was filled with flowable composite and
      the posts inserted into the mold. After photoactivation through the post and
      removal of unpolymerized material, the polymerization efficiency was estimated by
      percentage of mass gain (n=5). Data were analyzed using t-test (5%). RESULTS: The
      bond strength of the translucent post was higher than the opaque post for all
      root thirds. For both posts the bond strength at the cervical third was higher
      than at the middle and apical thirds. A predominance of adhesive failures was
      detected for all conditions. Mixed failures were more frequently observed for the
      opaque post. Almost all the composite polymerized and bonded to the extension of
      the translucent post, whereas polymerization of the composite was restricted to
      the cervical area of the opaque post. CONCLUSIONS: The use of translucent post
      may positively influence the polymerization efficiency and bond strength of resin
      cement to intraradicular dentin.

PMID- 23116924
TI  - Surfing the big WAVE: Insights into the role of WAVE3 as a driving force in
      cancer progression and metastasis.
AB  - WAVE3 belongs to the WASP/WAVE family of actin cytoskeleton remodeling proteins.
      These proteins are known to be involved in several biological functions ranging
      from controlling cell shape and movement, to being closely associated with
      pathological conditions such as cancer progression and metastasis. Last decade
      has seen an explosion in the literature reporting significant scientific advances
      on the molecular mechanisms whereby the WASP/WAVE proteins are regulated both in
      normal physiological as well as pathological conditions. The purpose of this
      review is to present the major findings pertaining to how WAVE3 has become a
      critical player in the regulation of signaling pathways involved in cancer
      progression and metastasis. The review will conclude with suggesting options for
      the potential use of WAVE3 as a therapeutic target to prevent the progression of
      cancer to the lethal stage that is the metastatic disease.

PMID- 23116927
TI  - Aseptic glenoid loosening or failure in total shoulder arthroplasty: revision
      with glenoid reimplantation.
AB  - HYPOTHESIS AND BACKGROUND: Reimplantation of a new glenoid component for
      symptomatic glenoid failure after total shoulder arthroplasty (TSA) is a well
      established surgical strategy. In case of aseptic glenoid loosening or failure,
      revision of TSA by reimplantation of a cemented glenoid implant would be a
      reliable therapeutic option. MATERIALS AND METHODS: This retrospective
      multicenter study included 42 TSAs with symptomatic failed glenoids revised by
      reimplantation of an all-polyethylene (PE), cemented glenoid component. All
      patients were reviewed clinically and radiologically, with a mean follow-up of 74
      months. RESULTS: The failed initial glenoid component was metal backed in 32
      cases and PE cemented in 10. The main cause of glenoid failure was component
      loosening in 19 cases (46%) and PE wear or dissociation in 23 (54%). Associated
      complications were very frequent, including rotator cuff tears, subscapularis
      insufficiency, and prosthesis instability. At last follow-up, 7 patients (17%)
      had already been re-revised because of symptomatic recurrent glenoid loosening.
      The overall rate of recurrent glenoid loosening (re-revision plus radiologic
      loosening) was 67%. Soft-tissue problems and prosthetic instability were
      significantly associated with recurrent loosening. Of the 10 associated bone
      grafts performed during the revision procedure, all were partially or totally
      lysed. At follow-up, the mean Constant score was 57 points (gain of 16 points)
      and the mean active anterior elevation was 125 degrees  (gain of 19 degrees ).
      CONCLUSION: This study suggests that revision of a TSA with reimplantation of an
      all-PE cemented glenoid component does not solve the problem of glenoid
      loosening. Soft-tissue failure and prosthetic instability are underestimated
      preoperatively and may explain, in part, the high rate of recurrent glenoid
      loosening.

PMID- 23116928
TI  - Nursing students' perspectives and suggestions on patient safety--implications
      for developing the nursing education curriculum in Iran.
AB  - BACKGROUND: Nursing students' close involvement in knowledge development about
      patient safety will enhance the integrity of the current content of nursing
      education and pave the way towards developing a nursing curriculum that
      facilitates achieving a safer health-care system. OBJECTIVES: This study explores
      nursing students' perspectives and suggestions on developing patient safety
      aspects of the nursing curriculum in the context of Iranian culture. DESIGN: A
      qualitative methodology involving three focus groups with a purposive sample of
      18 nursing students from a large Iranian nursing school, utilising directed semi
      structured interviews generated data, which was analysed using the content
      analysis process. RESULTS: Two main themes emerged from content analysis: (1)
      "involving students fully in patient care" with subthemes 'building a trusting
      relationship between education and practice', and 'promoting inter-dependence
      between health-care providers', and (2) "structuring patient safety education"
      with subthemes 'transforming nursing routines to evidence-based care', and
      'connecting care to patient safety issues'. CONCLUSIONS: The extent of students'
      involvement in clinical practice and clinical nurses' roles in student education
      in practice requires clarification. The curriculum needs to incorporate patient
      safety aspects throughout, and include interdisciplinary education to ensure
      compliance with patient safety policies. Moreover, successful implementation of
      such a curriculum necessitates cooperation from nursing practice and instructors
      to meet nursing students' expectations.

PMID- 23116929
TI  - Gastric incarceration after chest stab injury.

PMID- 23116930
TI  - Emergency Medicine resident anesthesia training in a private vs. academic
      setting.
AB  - BACKGROUND: Airway management is an essential part of any Emergency Medicine (EM)
      training program. Academic centers typically provide training to many learners at
      various training levels in a number of medical specialties during anesthesiology
      rotations. This potentially creates competition for intubation procedures that
      may negatively impact individual experiences. OBJECTIVES: We hypothesized that
      residents would report higher numbers of intubations and improved educational
      value in a private practice, rather than an academic, anesthesiology rotation.
      METHODS: EM residents' anesthesiology training was evaluated pre and post a
      change in training setting from an academic institution to a private practice
      institution. Outcome measures included the number of self-reported intubations,
      resident ratings of the rotation, and the number of positive comments. Residents'
      evaluation was measured with: a 14-item evaluation; subjective comments, which
      two blinded reviewers rated as positive, negative, or neutral; and transcripts
      from structured interviews to identify themes related to training settings.
      RESULTS: The number of intubations increased significantly in the private
      practice setting (4.6 intubations/day vs. 1.5 intubations/day, p < 0.001).
      Resident evaluations improved significantly with the private practice experience
      (mean scores of 3.83 vs. 2.23, p-values <0.05). Residents' impressions were also
      significantly higher for the private practice setting with respect to increased
      educational value, greater use of adjunct airway devices, and directed teaching.
      CONCLUSIONS: Number of intubations performed and residents' rating of the
      educational value were more favorable for a private practice anesthesiology
      rotation. Alternative settings may provide benefit for training in areas that
      have competition among trainees.

PMID- 23116931
TI  - Acute pulmonary and ischemic lower limb thromboembolism: a case of a paradoxical
      embolism.

PMID- 23116932
TI  - SOSMAT: single-operator scapular manipulation and traction-countertraction for
      reduction of anterior shoulder dislocation.

PMID- 23116933
TI  - Acute calcific tendinitis of the wrist.
AB  - BACKGROUND: Acute calcific tendinitis, a benign and self-limiting inflammatory
      condition commonly seen in the shoulder, is also described in many other tendons,
      including those in the hand and wrist. When involving the wrist, acute calcific
      tendinitis is often misdiagnosed and mistaken for infection. OBJECTIVE: We
      present this case to increase familiarity with this condition to avoid errors in
      diagnosis resulting in inappropriate treatment with antibiotics or even surgery.
      CASE REPORT: A 27-year-old man presented to the Emergency Department with a 2
      week history of volar wrist pain, with sudden increase in pain associated with
      chills and new onset swelling and redness of the wrist. Plain radiographs showed
      characteristic soft-tissue calcification overlying the insertion of the flexor
      carpi ulnaris tendon into the wrist. Treatment with ibuprofen and splinting
      resulted in complete symptom resolution. CONCLUSION: Acute calcific tendinitis is
      an important consideration in the differential diagnosis of acute wrist pain.
      Radiographs are helpful in confirming the diagnosis when symptoms and examination
      findings are characteristic.

PMID- 23116934
TI  - Development of a national public safety broadband network.

PMID- 23116935
TI  - The medical genetics of dystrophinopathies: molecular genetic diagnosis and its
      impact on clinical practice.
AB  - A large variety of mutations in the dystrophin gene cause Duchenne and Becker
      muscular dystrophies, diseases affecting predominantly the striated muscles
      (skeletal and cardiac). Rare mutations also account for the allelic disorder
      isolated X-linked dilated cardiomyopathy. Dystrophin protein is encoded by a huge
      gene located on the X chromosome and the understanding of its complex genomic
      architecture has unraveled general key functions in gene expression regulation.
      Dystrophin also exists as a number of other tissue specific isoforms, some
      exclusively or predominantly expressed in the brain and/or in other tissues.
      Genotype definition of the dystrophin gene in patients with dystrophinopathies
      has taught us much about functionally important domains of the protein itself and
      has also provided insights regarding several regulatory mechanisms governing the
      gene expression profile. This review focuses on the current understanding of the
      dystrophin mutations heterogeneity, genotype-phenotype correlations, as well as
      interpretation of the functional significance of mutations that often require non
      routine genetic studies. It also explores the impact of genetic diagnosis on
      clinical definition and on the discovery of biomarkers and personalized
      therapies. Our aim is to offer an overview of the medical genetic approach on the
      dystrophin gene and dystrophinopathies with implications for clinical practice
      and therapeutic perspectives.

PMID- 23116936
TI  - Predictors of absence of cervical intraepithelial neoplasia in the conization
      specimen.
AB  - OBJECTIVE: Over 10% of women who undergo conization for cervical intraepithelial
      neoplasia (CIN) show no lesion in the surgical specimen. We aimed to determine
      whether these patients can be identified before conization using clinical,
      virological and/or cyto-histological characteristics, to avoid unnecessary
      treatment. METHODS: Of 687 women with CIN treated by conization in the Hospital
      Clinic of Barcelona between 2008 and 2011, all patients (n=110, 16%) showing no
      lesion in the surgical specimen were included as the study group. The control
      group included a series of randomly selected women with CIN in the cone specimen
      (n=220). Pre-conization clinical characteristics as well as high-risk human
      papillomavirus (hr-HPV) status determined by Hybrid Capture 2 were analyzed as
      possible predictors of absence of lesion. RESULTS: A negative pre-conization hr
      HPV test or a low viral load (<10 relative light units) significantly increased
      the probability of absence of CIN in the conization specimen (75.0%, and 52%
      respectively) compared with patients with a high viral load (26.7%, p<0.001).
      This association was confirmed in the multivariate analysis (p<0.001). The risk
      of developing persistent/recurrent disease after treatment was significantly
      lower in patients with negative hr-HPV test or a low viral load (16.1% CIN1, 0%
      CIN2-3), than in patients with a high viral load (27.6% CIN1, 4.1% CIN2-3,
      p=0.031). CONCLUSION: Women with negative pre-conization hr-HPV test results or a
      low viral load have a high probability of having no lesion in the conization
      specimen. These patients should be excluded from immediate surgical excision and
      considered for follow-up.

PMID- 23116937
TI  - In vitro fertilization, endometriosis, nulliparity and ovarian cancer risk.
AB  - OBJECTIVES: To examine the risk of invasive epithelial ovarian cancer in a cohort
      of women seeking treatment for infertility. METHODS: Using whole-population
      linked hospital and registry data, we conducted a cohort study of 21,646 women
      commencing hospital investigation and treatment for infertility in Western
      Australia in the years 1982-2002. We examined the effects of IVF treatment,
      endometriosis and parity on risk of ovarian cancer and explored potential
      confounding by tubal ligation, hysterectomy and unilateral oophorectomy/salpingo
      oophorectomy (USO). RESULTS: Parous women undergoing IVF had no observable
      increase in the rate of ovarian cancer (hazard ratio [HR] 1.01; 95% confidence
      interval [CI] 0.35-2.90); the HR in women who had IVF and remained nulliparous
      was 1.76 (95% CI 0.74-4.16). Women diagnosed with endometriosis who remained
      nulliparous had a three-fold increase in the rate of ovarian cancer (HR 3.11; 95%
      CI 1.13-8.57); the HR in parous women was 1.52 (95% CI 0.34-6.75). In separate
      analyses, women who had a USO without hysterectomy had a four-fold increase in
      the rate of ovarian cancer (HR 4.23; 95% CI 1.30-13.77). Hysterectomy with or
      without USO appeared protective. CONCLUSIONS: There is no evidence of an
      increased risk of ovarian cancer following IVF in women who give birth. There is
      some uncertainty regarding the effect of IVF in women who remain nulliparous.
      Parous women diagnosed with endometriosis may have a slightly increased risk of
      ovarian cancer; nulliparous women have a marked increase in risk.

PMID- 23116938
TI  - Endocrine disruptive potential of endosulfan on the reproductive axis of
      Cichlasoma dimerus (Perciformes, Cichlidae).
AB  - Endosulfan (ES), a persistent organochlorine pesticide, is widely used despite
      its toxicity to non-target animals. Upon reaching water bodies, ES can cause
      negative effects on aquatic animals, including disruption of hormonal systems.
      However, the action of ES on fish reproductive axis has been hardly studied thus
      far. The aim of the present work was to assess the endocrine disruptive potential
      of endosulfan on the pituitary gonadotropins levels and on the testes function
      due to ES in the South American freshwater fish Cichlasoma dimerus, using in
      vitro and in vivo approaches. In vitro experiments showed that ES inhibited the
      LH-stimulated steroidogenesis in gonads; no change was observed in gonadotropins
      release from pituitaries in culture. Laboratory waterborne ES (0.1, 0.3 and 1
      MUg/L) exposure for two months caused decrease in betaFSH pituitary content and
      gammaGT activity in the testes (Sertoli cell function marker). Testicular
      histology revealed pathologies such as scarce intermediate stages of
      spermatogenesis, release of immature germ cells into the lobular lumen, presence
      of foam cells and interstitial fibrosis. As FSH and FSH-mediated steroidogenesis
      regulate spermatogenesis and Sertoli cell function, the effect of ES on FSH could
      be responsible for the morphological alterations observed in testes. In vitro, ES
      disrupted steroidogenesis in gonads, therefore similar effects in vivo cannot be
      ruled out. Based on this evidence, ES exhibits an endocrine disruptive action on
      the reproductive axis of C. dimerus, causing disruption at the pituitary and/or
      at the gonad level. These effects could acquire ecological significance under
      prolonged exposure to the pesticide in nature.

PMID- 23116939
TI  - In vitro fermentation of commercial alpha-gluco-oligosaccharide by faecal
      microbiota from lean and obese human subjects.
AB  - The fermentation selectivity of a commercial source of a-gluco-oligosaccharides
      (BioEcolians; Solabia) was investigated in vitro. Fermentation by faecal bacteria
      from four lean and four obese healthy adults was determined in anaerobic, pH
      controlled faecal batch cultures. Inulin was used as a positive prebiotic
      control. Samples were obtained at 0, 10, 24 and 36 h for bacterial enumeration by
      fluorescent in situ hybridisation and SCFA analyses. Gas production during
      fermentation was investigated in non-pH-controlled batch cultures. a-Gluco
      oligosaccharides significantly increased the Bifidobacterium sp. population
      compared with the control. Other bacterial groups enumerated were unaffected with
      the exception of an increase in the Bacteroides-Prevotella group and a decrease
      in Faecalibacterium prausnitzii on both a-gluco-oligosaccharides and inulin
      compared with baseline. An increase in acetate and propionate was seen on both
      substrates. The fermentation of a-gluco-oligosaccharides produced less total gas
      at a more gradual rate of production than inulin. Generally, substrates fermented
      with the obese microbiota produced similar results to the lean fermentation
      regarding bacteriology and metabolic activity. No significant difference at
      baseline (0 h) was detected between the lean and obese individuals in any of the
      faecal bacterial groups studied.

PMID- 23116940
TI  - The telocentric tandem repeat at the p-arm is not conserved in Mus musculus
      subspecies.
AB  - Mouse chromosomes, with the exception of the Y chromosome, are telocentric. The
      telomere at the p-arm is separated from the centromere by the tL1 sequence and
      TLC tandem repeats. A previous report showed that the TLC array was also
      conserved in other strains of the subgenus Mus. These results suggest that the
      TLC arrays promote the stable evolutionary maintenance of a telocentric karyotype
      in the subgenus Mus. In this study, we investigated the degree of conservation of
      TLC arrays among a variety of wild-derived inbred strains, all of which are
      descendants of wild mice captured in several areas of the world. Genomic PCR
      analysis indicates that the sequential order of telomere-tL1 is highly conserved
      in all strains, whereas tL1-TLC is not. Next, Southern blot analysis of DNAs
      isolated from a panel of mouse subspecies showed both Mus musculus domesticus and
      Mus musculus castaneus subspecies possess TLC arrays. Unexpectedly, this repeat
      appears to be lost in almost all Mus musculus musculus and Mus musculus
      molossinus subspecies, which show a clear geographic divide. These results
      indicate that either other unknown sequences were replaced by the TLC repeat or
      almost all M. m. musculus and M. m. molossinus subspecies do not have any
      sequence between the telomere and minor satellites. Our observation suggests that
      the TLC array might be evolutionarily unstable and not essential for murine
      chromosomal conformation. This is the first example of the subspecies-specific
      large genome alterations in mice.

PMID- 23116941
TI  - Cloning of galactinol synthase gene from Ammopiptanthus mongolicus and its
      expression in transgenic Photinia serrulata plants.
AB  - A cold induced galactinol synthase gene (AmGS) and its promoter sequence were
      identified and cloned from the cold-tolerant tree Ammopiptanthus mongolicus by
      using cDNA-AFLP, RACE-PCR and TAIL-PCR strategies combined with its expression
      pattern analysis after cold inducing treatment. Accession number of the AmGS gene
      in GenBank is DQ519361. The open reading frame (ORF) region of the AmGS gene is
      987 nucleotides encoding for 328 amino acid residues and a stop codon. The
      genomic DNA sequence of AmGS gene contains 3 exons and 2 introns. Moreover, a
      variety of temporal gene expression patterns of AmGS was detected, which revealed
      the up-regulation of AmGS gene in stresses of cold, ABA and others. Then the AmGS
      gene was transformed into Photinia serrulata tree by Agrobacterium-mediated
      transformation, and the transgenic plants exhibited higher cold-tolerance
      comparing with non-transformed plants.

PMID- 23116942
TI  - Sequence variation in the Mc1r gene for a group of polymorphic snakes.
AB  - Studying the genetic factors underlying phenotypic traits can provide insight
      into dynamics of selection and molecular basis of adaptation, but this goal can
      be difficult for non-model organisms without extensive genomic resources.
      However, sequencing candidate genes for the trait of interest can facilitate the
      study of evolutionary genetics in natural populations. We sequenced the
      melanocortin-1 receptor (Mc1r) to study the genetic basis of color polymorphism
      in a group of snake species with variable black banding, the genera Sonora,
      Chilomeniscus, and Chionactis. Mc1r is an important gene in the melanin synthesis
      pathway and is associated with ecologically important variation in color pattern
      in birds, mammals, and other squamate reptiles. We found that Mc1r nucleotide
      sequence was variable and that within our focal Sonora species, there are both
      fixed and heterozygous nucleotide substitutions that result in an amino acid
      change and selection analyses indicated that Mc1r sequence was likely under
      purifying selection. However, we did not detect any statistical association with
      the presence or absence of black bands. Our results agree with other studies that
      have found no role for sequence variation in Mc1r and highlight the importance of
      comparative data for studying the phenotypic associations of candidate genes.

PMID- 23116943
TI  - Genetic analysis of the TBX3 gene promoter in ventricular septal defects.
AB  - Congenital heart disease (CHD) is the most common birth defect in humans. Genetic
      causes and underlying molecular mechanisms for CHD remain largely unknown. T-box
      transcription factor 3 (TBX3) plays a critical role in the developing heart in a
      dose-dependent manner. TBX3 represses chamber myocardial gene expression.
      Mutations in TBX3 gene have been associated to ulnar-mammary syndrome with
      multiple developmental defects, including cardiac defects. We hypothesized that
      the sequence variants within TBX3 gene promoter that change TBX3 levels may
      mediate CHD development. In this study, TBX3 gene promoter was genetically
      analyzed in large cohorts of patients with ventricular septal defect (VSD)
      (n=325) and ethnic-matched healthy controls (n=359). Seven sequence variants,
      including two single-nucleotide polymorphisms (g.3863 C>T and g.4095G>T), three
      novel deletions (g.4433_4435del, g.4672_4675del and g.4820_4821del) and two novel
      insertions (g.3913_3914ins and g.4735_4736ins), were identified. Five of the
      seven variants were identified in VSD patients and controls with similar
      frequencies. Two other variants were found only in controls. These variants,
      which were observed in high frequencies, did not modify or interrupt the critical
      binding site for basic transcription factors. Taken together, these results
      suggested that the sequence variants within the TBX3 gene promoter did not
      contribute to VSD etiology.

PMID- 23116945
TI  - Adipose tissue inflammation in diabetes and heart failure.
AB  - Adipose tissue inflammation induces systemic insulin resistance in persons with
      obesity and heart failure, and has a crucial role in the progression of these
      diseases. Chronic inflammatory processes share a common mechanism in which
      increased production of reactive oxygen species activates p53 and NF-kappaB
      signaling, leading to up-regulation of pro-inflammatory cytokine expression and
      impairment of glucose metabolism. Since inhibition of these processes could slow
      the progression of various diseases, targeting adipose inflammation has the
      potential to become a new therapeutic approach for diabetes and heart failure.

PMID- 23116944
TI  - A unique host defense pathway: TRIF mediates both antiviral and antibacterial
      immune responses.
AB  - Both anti-viral and anti-bacterial host defense mechanisms involve TRIF
      signaling. TRIF provides early clearance of pathogens and coordination of a local
      inflammatory ensemble through an interferon cascade, while it may trigger organ
      damage. The multipotentiality of TRIF-mediated immune machinery may direct the
      fate of our continuous battle with microbes.

PMID- 23116946
TI  - Mesenchymal stem cells protect from sub-chronic phencyclidine insult in vivo and
      counteract changes in astrocyte gene expression in vitro.
AB  - Mesenchymal stem cells (MSCs) are an attractive cell source for regenerative
      medicine strategies in brain diseases. Experimental studies have shown that
      repeated administration of phencyclidine (PCP) leads to schizophrenia-like
      behavioral changes in mice. The aim of the present study was to explore the
      effectiveness of MSC transplantation into the hippocampus in attenuating PCP
      induced social behavior deficits. PCP was administered subcutaneously to C57bl
      mice (10mg/kg daily) for 2 weeks. On the first day of PCP administration, adult
      human MSCs were transplanted into the hippocampus. A week after the last PCP
      dose, the mice underwent social preference testing. MSC transplantation was
      associated with a significant reduction in the adverse social behavior induced by
      PCP. Immunohistochemical analysis revealed that the stem cells survived in the
      mouse brain, and hippocampal Western blot analysis revealed a statistical trend
      towards a decrease in cleaved caspase 3 protein levels in the stem cell treated
      group. Upon in vitro co-culture of astrocytes and MSCs, the MSCs, in the presence
      of PCP, positively regulated astrocyte expression of genes involved in glutamate
      metabolism and antioxidant defenses. These findings suggest that MSC
      transplantation into the hippocampus may serve as a novel neuroprotective tool
      for the treatment of the PCP-induced schizophrenia-like social endophenotype. The
      mechanism underlying the beneficial behavioral effect may involve modulation of
      host astrocyte functioning, including glutamate processing and antioxidant
      capacity.

PMID- 23116947
TI  - Technology, policy, and personal decision making.

PMID- 23116948
TI  - Directive counseling about becoming pregnant.

PMID- 23116949
TI  - Protecting the confidentiality of sexually active adolescents.

PMID- 23116950
TI  - Sex selection for nonhealth-related reasons.

PMID- 23116951
TI  - Funding for abortion training in OB/GYN residency.

PMID- 23116952
TI  - The American Medical Association Code of Medical Ethics' opinions on confidential
      care for sexually active minors and physicians' exercise of conscience in refusal
      of services.

PMID- 23116953
TI  - Barriers and biases: ethical considerations for providing emergency contraception
      to adolescents in the emergency department.

PMID- 23116955
TI  - Legislative restrictions on abortion.

PMID- 23116954
TI  - Male hormonal contraception.

PMID- 23116956
TI  - The religious exemption to mandated insurance coverage of contraception.

PMID- 23116957
TI  - Contraceptive justice: why we need a male pill.

PMID- 23116958
TI  - Federal sterilization policy: unintended consequences.

PMID- 23116959
TI  - Selecting the traits of children prior to birth.

PMID- 23116961
TI  - Nutraceuticals as new treatment approaches for oral cancer--I: Curcumin.
AB  - Oral squamous cell carcinoma (OSCC) is a growing global public health problem for
      which standard therapeutic strategies have failed to contribute significantly to
      improve the survival rates that have remained around 50% over the past three
      decades. Therefore, there is a pressing need for new therapeutic strategies.
      Curcumin is a natural dietary compound with known anti-neoplastic activities,
      hence its classification as a nutraceutical agent. This review presents the
      current in vitro and in vivo studies in which curcumin has been examined for its
      anti-cancer potential in treating OSCC. Its mechanisms of action are also
      beginning to become unveiled. The available studies have been focusing on the
      impact of curcumin on epithelial malignant cells, but overlooking the components
      of the tumor microenvironment. Curcumin has been emerging as a promising
      therapeutic agent in oral cancer, either alone or in combination with standard
      therapeutic agents, and will probably become of practical use once its route of
      administration has overcome its poor bioavailability.

PMID- 23116962
TI  - Nodal recurrence of sinonasal cancer: does the risk of cervical relapse justify a
      prophylactic neck treatment?
AB  - BACKGROUND: Sinonasal cancers are rare and no high-level evidence exists to
      determine their optimal management. Prophylactic neck treatment issue remains
      controversial. The aim of this study was to analyze the pattern of neck failure
      and to identify any prognostic factors that may influence neck control. METHODS:
      A retrospective review of 155 consecutive patients treated for sinonasal
      malignancy, without prophylactic neck treatment, between 1995 and 2005 at
      tertiary cancer center was performed. Demographic, clinical, morphological and
      pathological parameters were correlated with oncologic outcomes. RESULTS: Eight
      out of 155 patients (5%) presented initially with neck node metastasis. Complete
      remission was obtained for 133 patients after treatment completion. During follow
      up, 16 out of 133 patients (12%) were affected with regional recurrence. Neck
      failure occurred in 8 out of 51 patients with local failure and in 8 out of 82
      patients locally controlled. Isolated nodal failure was observed in 5 patients
      initially cN0 out of 133 (3.8%) representing 7.3% of all recurrences and 3 of
      them underwent successful salvage therapy. None of the tested factors were
      significantly associated with neck control (p>0.05). Lymph node at diagnosis time
      was significantly and independently associated with poor survival (p=0.0012).
      CONCLUSION: Isolated neck relapse, when local control is achieved, is rare and
      salvage treatment is effective. Routine prophylactic neck treatment has little
      interest. However, this approach could be profitable to few selected patients,
      who remain to be defined. Further investigations are needed.

PMID- 23116963
TI  - Treatment of acute mania with methylphenidate: therapeutic approach based on a
      new pathophysiological model.

PMID- 23116964
TI  - Molecular cloning and characterization of sea bass (Dicentrarchus labrax, L.) MHC
      class I heavy chain and beta2-microglobulin.
AB  - In this work, the gene and cDNA of sea bass (Dicentrarchus labrax) beta2
      microglobulin (Dila-beta2m) and several cDNAs of MHC class I heavy chain (Dila
      UA) were characterized. While Dila-beta2m is single-copy, numerous Dila-UA
      transcripts were identified per individual with variability at the peptide
      binding domain (PBD), but also with unexpected diversity from the connective
      peptide (CP) through the 3' untranslated region (UTR). Phylogenetic analysis
      segregates Dila-beta2m and Dila-UA into each subfamily cluster, placing them in
      the fish class and branching Dila-MHC-I with lineage U. The alpha1 domains
      resemble those of the recently proposed L1 trans-species lineage. Although no
      Dila-specific alpha1, alpha2 or alpha3 sub-lineages could be observed, two highly
      distinct sub-lineages were identified at the CP/TM/CYT regions. The three
      dimensional homology model of sea bass MHC-I complex is consistent with other
      characterized vertebrate structures. Furthermore, basal tissue-specific
      expression profiles were determined for both molecules, and expression of beta2m
      was evaluated after poly I:C stimulus. Results suggest these molecules are
      orthologues of other beta2m and teleost classical MHC-I and their basic structure
      is evolutionarily conserved, providing relevant information for further studies
      on antigen presentation in this fish species.

PMID- 23116965
TI  - Antiarrhythmic effects of (-)-epicatechin-3-gallate, a novel sodium channel
      agonist in cultured neonatal rat ventricular myocytes.
AB  - (-)-Epicatechin-3-gallate (ECG), a polyphenol extracted from green tea, has been
      proposed as an effective compound for improving cardiac contractility. However,
      the therapeutic potential of ECG on the treatment of arrhythmia remains unknown.
      We investigated the direct actions of ECG on the modulation of ion currents and
      cardiac cell excitability in the primary culture of neonatal rat ventricular
      myocyte (NRVM), which is considered a hypertrophic model for analysis of
      myocardial arrhythmias. By using the whole-cell patch-clamp configurations, we
      found ECG enhanced the slowly inactivating component of voltage-gated Na(+)
      currents (I(Na)) in a concentration-dependent manner (0.1-100 MUM) with an EC(50)
      value of 3.8 MUM. ECG not only shifted the current-voltage relationship of peak
      I(Na) to the hyperpolarizing direction but also accelerated I(Na) recovery
      kinetics. Working at a concentration level of I(Na) enhancement, ECG has no
      notable effect on voltage-gated K(+) currents and L-type Ca(2+) currents. With
      culture time increment, the firing rate of spontaneous action potential (sAP) in
      NRVMs was gradually decreased until spontaneous early after-depolarization (EAD)
      was observed after about one week culture. ECG increased the firing rate of
      normal sAP about two-fold without waveform alteration. Interestingly, the
      bradycardia-dependent EAD could be significantly restored by ECG in fast firing
      rate to normal sAP waveform. The expression of dominant cardiac sodium channel
      subunit, Nav1.5, was consistently detected throughout the culture periods. Our
      results reveal how ECG, the novel I(Na) agonist, may act as a promising candidate
      in clinical applications on cardiac arrhythmias.

PMID- 23116966
TI  - Growth hormone level at admission and its evolution during refeeding are
      predictive of short-term outcome in restrictive anorexia nervosa.
AB  - The growth hormone (GH)-insulin-like growth factor-1 (IGF-1) axis is dramatically
      altered in patients with anorexia nervosa (AN). The aim of the present study was
      to investigate whether GH and IGF-1 could be predictors of outcome in patients
      with a restrictive form of AN. Blood levels of GH, IGF-1, adipocytokines,
      ghrelin, insulin, glucose, and sex and thyroid hormones were measured in eleven
      women inpatients with AN and in ten healthy women controls. Three stages were
      compared during refeeding: admission (T0), when BMI reached 16 kg/m2 (T1) and at
      discharge when BMI reached 17.5 kg/m2 (T2). Clinical status was assessed 6 months
      after discharge from hospital (T3), and remission was defined by the maintenance
      of a BMI > or = 17.5 kg/m2. AN patients in remission (AN-R; n 6) had
      significantly higher GH levels at admission than those who relapsed (AN-NR; n 5)
      (P < 0.05). During refeeding (delta = T2 - T0), the AN-R group differed from the
      AN-NR group only by both GH level decrease (P < 0.05) and BMI increase (P <
      0.05). In multiple regression analysis, delta GH was associated negatively and
      significantly and delta leptin and delta body fat mass levels were associated
      positively and significantly with BMI at T3 and explained 88% of its variability
      (r2 0.88, P < 0.05). The present study suggests that a low GH level at admission
      and the absence of its decrease after weight recovery could predict short-term
      relapse in women suffering from a restrictive form of AN.

PMID- 23116967
TI  - The relationship between sexual functioning among couples undergoing infertility
      treatment: a pair of perfect gloves.
AB  - OBJECTIVE: The study aimed to measure the relationship of sexual functioning
      between male and female partners, who sought infertility treatment in a
      university hospital setting in Malaysia. METHODS: This cross-sectional study was
      conducted on couples with infertility problems attending the Medically Assisted
      Conception Center (MACC). The female and male sexual functioning was measured
      using the Malay Version of Female Sexual Function Index (MVFSFI) and Malay
      Version of International Index of Erectile Function (IIEF), respectively. The
      relationship between the female and male sexual functioning was measured using
      correlation statistical analyses. A total of 269 subjects (150 females and 119
      males) who met the requirement of the study, were recruited. RESULTS: The female
      and male sexual functioning was moderately correlated (r=0.574). Female sexual
      arousal and sexual satisfaction domains scores had the largest correlation
      (r=0.522 and r=0.507 respectively) to IIEF total score. On the other hand, male
      intercourse satisfaction (IS) domain score had the highest correlation (r=0.574)
      to FSFI total score. A strong correlation between male and female sexual function
      was observed. CONCLUSION: It is speculated that possible interaction of male and
      female sexual functioning may be multifactorial and complex.

PMID- 23116968
TI  - Chemical Safety for Sustainability (CSS): human in vivo biomonitoring data for
      complementing results from in vitro toxicology--a commentary.
AB  - The U.S. Environmental Protection Agency (EPA) has instituted the Chemical Safety
      for Sustainability (CSS) research program for assessing the health and
      environmental impact of manufactured chemicals. This is a broad program wherein
      one of the tasks is to develop high throughput screening (HTS) methods and follow
      up confirmation for toxicity at realistic environmental exposure levels. The main
      tools under this task are in vitro toxicity testing, in silico molecular
      modeling, and in vivo (systemic) measurements documentation. The in vivo research
      component is intended to support and corroborate in vitro chemical toxicity
      prioritization with observations of systemic perturbations and statistical
      parameters derived from intact (living) organisms. Based on EPA's Biomonitoring
      Framework for human health research, such observations are intended to link
      environmental exposures to a cascade of biomarker chemicals to help identify and
      clarify adverse outcome pathways within the context of systems biology. This
      commentary discusses the issues regarding interpretation of in vitro changes from
      HTS as an adverse result, an adaptive (non-adverse) response, or a
      random/irrelevant occurrence. A second goal is to inform in vitro strategies as
      to relevant dosing (potency) levels at the cellular level that reflect realistic
      systemic exposures. Although we recognize the high value of in vivo animal
      toxicity testing, herein we focus on observational (minimally invasive) human
      biomonitoring methods and propose complementary in vivo testing that could help
      guide the design of high-throughput analyses and the ultimate interpretation of
      their outcomes.

PMID- 23116969
TI  - Communication guidelines as a learning tool: an exploration of user preferences
      in general practice.
AB  - OBJECTIVE: To explore characteristics of written communication guidelines that
      enhance the success of training aimed at the application of the recommendations
      in the guidelines. METHODS: Seven mixed focus groups were held consisting of
      communication skill teachers and communication skill learners and three groups
      with only learners. Analysis was done in line with principles of grounded theory.
      RESULTS: Five key attributes of guidelines for communication skill training were
      identified: complexity, level of detail, format and organization, type of
      information, and trustworthiness/validity. The desired use of these attributes is
      related to specific educational purposes and learners' expertise. The low
      complexity of current communication guidelines is appreciated, but seems ad odds
      with the wish for more valid communication guidelines. CONCLUSIONS: Which
      guideline characteristics are preferred by users depends on the expertise of the
      learners and the educational purpose of the guideline. PRACTICE IMPLICATIONS:
      Communication guidelines can be improved by modifying the key attributes in line
      with specific educational functions and learner expertise. For example: the
      communication guidelines used in GP training in the Netherlands, seem to offer an
      oversimplified model of doctor patient communication. This model may be suited
      for undergraduate learning, but does not meet the validity demands of physicians
      in training.

PMID- 23116971
TI  - Contradictory results of a more extensive search on cruciferous vegetables and
      breast cancer.

PMID- 23116972
TI  - Fire-related injuries with inpatient care in Finland: a 10-year nationwide study.
AB  - The aim of this study was to examine fire-related injuries leading to inpatient
      care in Finland. The Finnish National Hospital Discharge Register (2000-2009) and
      a sample of 222 patients from the Helsinki Burn Centre who sustained flame burns
      was used. During the 10-years study period, the incidence of fire-related
      injuries with inpatient care was approximately 5.6 per 100000 persons-years
      (n=295; males 74%, females 26%). Approximately three quarters involved burns and
      the remaining cases were mostly combustion gas poisonings. Burns declined from
      5.4 in 2000 to 4.0 per 100000 person-years in 2009. The decline was accounted for
      by young people primarily. Socio-economic features and smoking habits differ
      between the injured and general population. House fire victims were mainly middle
      aged and older, while injures involving flammable substances, campfires, etc.,
      were mostly associated with young people. House fires caused the worst damage in
      terms of Total Body Surface Area burned and inhalation burns. Significantly more
      people die on the scene of the incident than during the hospital care. Targeting
      preventive measures in particular at older people and those with a tendency for
      alcohol abuse and smoking could potentially reduce the burden of the most severe
      flame burns.

PMID- 23116970
TI  - Multidisciplinary approach to breast cancer diagnosed during pregnancy: maternal
      and neonatal outcomes.
AB  - AIM: We assessed maternal and neonatal outcome in women diagnosed with breast
      cancer during pregnancy. PATIENTS AND METHODS: Retrospective single-centre cohort
      study of 25 consecutive pregnant women (mean age 36 years) diagnosed and treated
      for breast cancer between 2000 and 2011. Management was individualized according
      to type of tumor and time of gestation at diagnosis. RESULTS: Twelve patients
      were diagnosed during the second trimester. BI-RADS category <3 mammographic
      lesions were diagnosed in 7 patients. A suspicious area was detected by
      ultrasound in 20 of 21 women who underwent ultrasound studies. Nineteen patients
      had positive hormone receptors and 7 sobreexpressed HER2. One patient was in
      stage 0, 8 in stage I, 8 in stage II, 3 in stage III and 5 in stage IV. Four
      patients decided voluntarily to legally terminate their pregnancies, one had a
      spontaneous miscarriage and in three patients, pregnancy was interrupted at the
      end of the third trimester before oncological treatment. Eleven patients were
      treated with chemotherapy during pregnancy after the second trimester using
      anthracycline-based regimens. In five patients the pregnancy was ended before 34
      weeks of gestation. Nine patients had gestation-related complications, including
      preterm labor, pneumonia, increase in velocity of the middle cerebral artery,
      oligohydramnios, preeclampsia, extreme prematurity, intrauterine growth
      restriction, dyspnea, spontaneous miscarriage and chemotherapy-related
      granulocytopenia. Betamethasone to stimulate fetal lung maturation was used in 6
      patients. CONCLUSION: Breast cancer women diagnosed during pregnancy presented a
      high number of complications unrelated to antineoplastic treatment. A
      multidisciplinary team approach is necessary for satisfactory neonatal results.

PMID- 23116973
TI  - EZH2 is regulated by ERK/AKT and targets integrin alpha2 gene to control
      Epithelial-Mesenchymal Transition and anoikis in colon cancer cells.
AB  - Epithelial-Mesenchymal Transition is a good example of cell plasticity. In
      tumorigenesis, this process has been associated with metastasis. Overexpression
      of EZH2 has been detected in most malignant human tumors, including colorectal
      carcinomas. Herein, we provide evidence supporting the idea that oncogenic
      Epithelial-Mesenchymal Transition in colon cancer cell models is partially
      controlled by epigenetic factors such as the transcription regulator EZH2.
      Evaluation of EZH2 mRNA and protein levels revealed overexpression in cell lines
      with metastatic traits. Analysis of EZH2 mRNA expression was expanded in clinical
      samples of colon cancer, and high level of EZH2 correlates with appearance of
      metastasis. Furthermore, inhibition of ERK and AKT pathways in metastatic colon
      cancer cell lines attenuates EZH2 overexpression. EZH2 promoter analysis
      illustrates presence of putative AP-1 binding sites and occupancy of
      transcription factors such as FRA-1 and C-JUN is demonstrated here on EZH2
      promoter. Abrogation of EZH2 expression impairs the ability of colon cancer cells
      to move associated with anoikis in three-dimensional environment. Integrin alpha2
      was identified to be a novel EZH2 target by chromatin immunoprecipitation and
      short hairpin RNA analysis. This study proposes that activation of ERK/AKT
      pathways and FRA1/C-JUN induce EZH2 overexpression, which results in Integrin
      alpha2 silencing. Our results show how deregulation of epigenetic factors and
      mechanisms can affect cancer cell aggressiveness and propose EZH2 as a potential
      metastasis marker and/or therapeutic target for colorectal cancer treatment.

PMID- 23116974
TI  - Uterine epithelial cells: Serving two masters.
AB  - Uterine epithelial cells are unique cells in that they are both epithelial in the
      typical barrier sense but in many mammalian species, they characteristically
      allow the blastocyst to penetrate them from the apical surface. Here we examine
      how these cells subserve both functions and in particular we synthesize recent
      evidence on focal adhesions and how these membrane structures contribute to
      uterine receptivity for blastocyst implantation. Focal adhesions emerge as a
      dynamic new player in the 'plasma membrane transformation' of early pregnancy and
      uterine receptivity in that they disassemble at the time of implantation in
      common with many other structures on the basolateral plasma membrane of these
      cells.

PMID- 23116975
TI  - Grip strength in a cohort of older medical inpatients in Malaysia: a pilot study
      to describe the range, determinants and association with length of hospital stay.
AB  - Grip strength is a marker of sarcopenia, the age-related decline in muscle mass
      and function, and has been little researched in Asian populations. We aimed to
      describe the feasibility and acceptability of measuring grip strength in
      hospitalized, older people in Malaysia and to explore its range, determinants and
      association with length of stay. Patients admitted acutely to the geriatrics ward
      of a teaching hospital were consecutively recruited. Inability to consent or use
      the dynamometer led to exclusion. Maximum grip strength, anthropometric data,
      length of hospital stay, discharge destination, 3-point Barthel score, mini
      mental state examination, falls history and number of co-morbidities and
      medications on admission were recorded. 80/153 (52%) eligible patients were
      recruited (52 women; age range 64-100 years). 9/153 (6%) refused to participate
      and 64/153 (42%) were excluded (34 too unwell, 24 unable to consent, 4 unable to
      use the dynamometer, 2 other reasons). 76/80 patients (95%) reported that they
      would undergo grip strength measurement again. Determinants were similar to those
      of Caucasian populations but grip strength values were lower. After adjustment
      for sex, age and height, stronger grip strength was associated with shorter
      length of stay [hazard ratio 1.05 (95% CI 1.00, 1.09; P=0.03)]. This is the first
      report of grip strength measurement in hospitalized older people in Malaysia. It
      was feasible, acceptable to participants and associated with length of stay.
      Further research is warranted to elucidate the normative range in different
      ethnic groups and explore its potential use in clinical practice in Malaysia.

PMID- 23116976
TI  - History of depression prior to Alzheimer's disease and vascular dementia verified
      post-mortem.
AB  - The aim of this study was to analyze the medical history, with regards to
      previous remote depression, in patients with neuropathologically verified
      Alzheimer's disease (AD), vascular dementia (VaD) and mixed AD/VaD. The 201
      patients included (115 AD, 44 VaD and 42 mixed AD/VaD) had been referred to the
      Psychogeriatric/Psychiatric Department, Lund University Hospital, for
      psychogeriatric investigation and were followed-up with clinical records and
      detailed information on psychiatric history prior to the onset of dementia.
      Depression was considered to exist when the patient had consulted a psychiatrist
      or physician and had been diagnosed with a "depressive episode" or "depression"
      and when anti-depressants and/or other specific treatments had been prescribed.
      Twenty patients (10%) had suffered from depression earlier in life well before
      the onset of dementia. Eight of the 9 AD patients with a previous diagnosis of
      depression had suffered from only one depressive episode and all had responded
      well to treatment, with complete recovery. In the VaD group, 8 out of 9 patients
      suffered two or more depressive episodes and only two recovered completely.
      Events with a possible significant relationship to depression were seen in 8 of
      the 9 AD patients but in only 1 of the 9 VaD patients. Psychotic symptoms were
      more common in VaD than in the AD group. The treatment modality of depression was
      similar in the groups. In conclusion, a history of depression prior to dementia
      is more common and more therapy-resistant in VaD than in AD.

PMID- 23116977
TI  - Homebound status increases death risk within two years in the elderly: results
      from a national longitudinal survey.
AB  - Homebound status is associated with poorer physical and mental health, as well as
      disability in the elderly. We aimed to examine the prevalence and the role of
      homebound status on mortality in a representative sample of the French non
      institutionalized population. This study included 7497 people aged 65 and over
      who were interviewed in 1999 and 2001 about the consequences of health problems
      on activities of daily living. Homebound status was defined as staying
      permanently inside the home, excluding an accident or a temporary illness. The
      influence of the homebound status on two-year mortality was assessed in a
      logistic regression model adjusted for the main confounders (age, sex, living as
      a couple, physical and mental impairments). The prevalence of homebound status
      was 4.7% (95% CI: 3.9-5.4) in this study. The number of homebound elderly was
      estimated at 421000 in France. The prevalence of homebound status increases with
      age and reaches 33.9% in people aged 95-99 years (95% CI: 13.1-54.6). Compared to
      non-homebound subjects, homebound elderly were more likely to be female, widower,
      to live alone and to have had a former low level job. Homebound status was
      associated with a number of physical and mental impairments. It increased the
      risk of dying within two years with an adjusted OR 3.45 (95% CI: 2.66-4.46).
      Homebound status should be considered as an indicator of frailty and used in the
      identification of old people likely to benefit from preventive interventions.

PMID- 23116978
TI  - Development and validation of a Chinese version of the Falls Efficacy Scale
      International.
AB  - The FES-I is an instrument developed to assess concern about falls. The aim of
      this study was to develop a Chinese version of the 16-item Falls Efficacy Scale
      International (FES-I(Ch)) and evaluate its structure, measurement properties and
      convergent and predictive validity. The FES-I(Ch) was developed following the
      recommended 10-step protocol. The FES-I(Ch) was then administered to 399
      community-dwelling Chinese older people (61-93 years) in conjunction with a range
      of other socio-demographic, physical, medical and functional measures. Falls were
      prospectively monitored over 12 months. Sub-samples were reassessed for
      determination of the FES-I(Ch)'s test-retest and inter-rater reliability. The
      overall structure and measurement properties of the FES-I(Ch), as evaluated with
      factor analysis and item-total correlations, was good. Internal consistency was
      excellent (Cronbach's alpha=0.94), as was test-retest and inter-rater reliability
      (ICC(3,1)=0.89 and ICC(2,1)=0.95 respectively). FES-I(Ch) scores were
      significantly higher in participants with poor physical performance, depression,
      medical conditions associated with falls and disability indicating acceptable
      congruent validity. FES-I(Ch) scores did not differ between those who did and did
      not fall in the 12-month follow-up period. We found that the FES-I(Ch) is a valid
      and reliable measure of concern about falls in Chinese older people. The
      relatively high level on concern (high FES-I(Ch) scores) as well as relatively
      few prospective falls may explain the lack of association between FES-I(Ch)
      scores and falls in this population. Future studies should explore the FES
      I(Ch)'s responsiveness to change over time and during intervention studies.

PMID- 23116979
TI  - Quality allied health clinical supervision policy in Australia: a literature
      review.
AB  - Clinical supervision is presented as a complex set of skills that may broadly
      apply to any and all allied health professions. However, it is also noted that a
      clear understanding of clinical supervision and how to implement it in allied
      health is currently lacking. It is argued that there is a need to reflect upon
      current approaches to clinical supervision amongst allied health professionals
      and to gain a shared understanding about what supervision involves, what
      effective supervision is, and what effective implementation of clinical
      supervision might look like. By gaining an understanding of what high quality
      clinical supervision is and how it is best put into practice, it is anticipated
      that this will form the first step in developing an understandable and useful
      universal supervision policy for all allied health professionals.

PMID- 23116980
TI  - Posttranslational modifications and assembly of septin heteropolymers and higher
      order structures.
AB  - Septins are cytoskeletal elements that contain a highly conserved canonical G
      domain flanked by more divergent N- and C-termini. Septin monomers form
      heteropolymers that in turn associate into a variety of higher-order structures.
      SUMOylation, acetylation and phosphorylation of septins have all been reported;
      however, there are no examples of residues that are universally modified
      suggesting that posttranslational modifications of septins evolved relatively
      recently. Within the conserved G domain, posttranslational modifications cluster
      in regions near the G interface, consistent with roles in modulating
      heteropolymer assembly. Within the highly diverged N- and C-termini,
      posttranslational modifications are scattered randomly, consistent with roles in
      modulating assembly of higher-order structures that are unique to individual
      organisms.

PMID- 23116981
TI  - [Use of ketamine sedation during painful treatment in children].

PMID- 23116982
TI  - [Esophageal strictures in children with epidermolysis bullosa].
AB  - Esophageal stricture is a rare but often severe complication of recessive
      dystrophic epidermolysis bullosa in children. The purpose of the study was to
      review this digestive complication with emphasis on diagnostic modalities and
      therapeutic management. PATIENTS AND METHODS: This was a retrospective study of
      two pediatric cases of esophageal stenosis that occurred during generalized
      recessive dystrophic epidermolysis bullosa of the Hallopeau-Siemens type.
      RESULTS: The 2 patients were aged 8 years 8 months and 11 years 5 months,
      respectively. Dysphagia was of early onset, before the age of 10 years in both
      cases. Esophageal opacification led to the diagnosis of esophageal stenosis
      located in the upper 1/3 of the esophagus in 1 case and at the junction between
      the middle and the lower 1/3 of the esophagus in the other case. None of the 2
      patients received medical treatment, and pneumatic dilation was the treatment
      method that was advocated. Esophageal endoscopy showed the stenosis and helped
      guide the positioning of the balloon catheter. These patients underwent 2 and 3
      sessions of dilation, respectively, at intervals of 2 months and 1 year. Balloon
      dilation has allowed the patients to have a more comfortable life with decreased
      dysphagia and a substantial improvement in nutritional status. However, this
      improvement was transient (1 patient had symptomatic recurrence of stenosis after
      3 years), which shows that monitoring of the patients and the resumption of
      dilatation sessions may be necessary. CONCLUSION: Esophageal strictures in
      dystrophic epidermolysis bullosa of the Hallopeau-Simens type are severe and
      difficult to support. Pneumatic dilatation is the treatment of choice for the
      fragile esophagus. It gives satisfactory results and can be repeated without
      significant risk.

PMID- 23116983
TI  - [Should a lumbar puncture be performed in any child with acute peripheral facial
      palsy and clinical suspicion of Lyme borreliosis?].
AB  - Lyme borreliosis should be considered in any child affected with acute peripheral
      facial palsy without obvious cause in endemic areas, especially if it happens
      from May to November, with a history of erythema migrans, tick bite, or possible
      exposure during the previous weeks. The clinical appearance of Lyme borreliosis
      differs between adults and children and according to the geographical origin of
      the infection: therefore it is difficult to interpret and follow the
      recommendations for the management and treatment of this disease.
      Neuroborreliosis is more frequent in Europe than in the United States, and
      meningitis associated to facial palsy occurs earlier and is more frequent among
      the European pediatric population, too. When peripheral facial palsy occurs and
      there is suspicion of Lyme borreliosis, it seems necessary to perform a lumbar
      puncture in order to support the diagnosis with detection of intrathecal
      synthesis of specific antibodies, sometimes more abundant than in the serum, and
      thus to adapt the antibiotic therapy modalities. Parenteral antibiotherapy is
      recommended if any involvement is detected in the cerebrospinal fluid, while oral
      antibiotherapy should be prescribed for isolated facial palsies. Follow-up should
      be made according to clinical symptoms with a close collaboration between
      pediatricians, infection disease specialists, and ENT specialists.

PMID- 23116984
TI  - [Intrathoracic acute appendicitis. A case report].
AB  - Intrathoracic appendicitis is an uncommon diagnosis. We report the case of a 6
      year-old boy with elevated CRP and no fever, who complained of nonspecific
      abdominal pain. A diaphragmatic hernia was suspected on a chest X-ray and
      confirmed by an ultrasound examination. A multidetector CT scan revealed
      intrathoracic acute appendicitis associated with a right posterolateral Bochdalek
      hernia. Abdominal diseases associated with late-presenting congenital
      diaphragmatic hernia are often manifested by an atypical clinical presentation,
      which can be a source of delay or error in diagnosis. We recommend radiological
      exploration in the case of diaphragmatic hernia, even with subtle clinical
      findings in the search of associated gastrointestinal complications.

PMID- 23116985
TI  - Reply to 'Comment on effects of statin therapy on abdominal aortic aneurysm
      growth: a meta-analysis and meta-regression of observational comparative
      studies'.

PMID- 23116987
TI  - Response to letter to the editor: 'Factors influencing wound healing of critical
      ischaemic foot after bypass surgery: is the angiosome important in selecting
      bypass target artery?'.

PMID- 23116988
TI  - Commentary on 'Autonomy following revascularization in 80-year-old patients with
      critical limb ischaemia'.

PMID- 23116989
TI  - Comment on: 'Factors influencing wound healing of critical ischaemic foot after
      bypass surgery: is the angiosome important in selecting bypass target artery?'.

PMID- 23116990
TI  - Midterm outcomes of embolisation of internal iliac artery aneurysms.
AB  - OBJECTIVES: There is no standardised technique for internal iliac artery aneurysm
      (IIAA) embolisation and results of long-term prevention of rupture are unknown.
      DESIGN: We retrospectively evaluated technical aspects and results of IIAA
      embolisation in a multicentre study. METHODS: Aneurysm morphology and
      embolisation techniques were reviewed. Aneurysm-related death, rupture, diameter
      increase, endoleak, secondary procedure and complication related to the IIA
      occlusion were recorded. RESULTS: Between 2001 and 2011, 53 patients with 57 IIAA
      were treated. Mean diameter of IIAA was 41 mm (range: 25-88 mm). Embolisation
      techniques were distal and proximal occlusion (n = 24), proximal occlusion (n =
      18) and sac packing (n = 15). Cumulative overall survival rate was 92% at 1 year,
      83% at 3 years and 59% at 5 years. No cause of deaths was related to aneurysm.
      Aneurysm diameter increased in five patients and endoleak was observed in 11
      patients. One secondary open conversion and five secondary endovascular
      procedures were performed for increase of diameter or proximal endoleak. Two
      patients experienced a disabling buttock claudication. CONCLUSIONS: Embolisation
      of IIAA is safe in the short- and midterm. However, endoleak and aneurysm
      diameter increases are not rare. Yearly post-procedure computed tomography
      angiography seems appropriate.

PMID- 23116991
TI  - Measuring neurophysiological signals in aircraft pilots and car drivers for the
      assessment of mental workload, fatigue and drowsiness.
AB  - This paper reviews published papers related to neurophysiological measurements
      (electroencephalography: EEG, electrooculography EOG; heart rate: HR) in
      pilots/drivers during their driving tasks. The aim is to summarise the main
      neurophysiological findings related to the measurements of pilot/driver's brain
      activity during drive performance and how particular aspects of this brain
      activity could be connected with the important concepts of "mental workload",
      "mental fatigue" or "situational awareness". Review of the literature suggests
      that exists a coherent sequence of changes for EEG, EOG and HR variables during
      the transition from normal drive, high mental workload and eventually mental
      fatigue and drowsiness. In particular, increased EEG power in theta band and a
      decrease in alpha band occurred in high mental workload. Successively, increased
      EEG power in theta as well as delta and alpha bands characterise the transition
      between mental workload and mental fatigue. Drowsiness is also characterised by
      increased blink rate and decreased HR values. The detection of such mental states
      is actually performed "offline" with accuracy around 90% but not online. A
      discussion on the possible future applications of findings provided by these
      neurophysiological measurements in order to improve the safety of the vehicles
      will be also presented. 

PMID- 23116992
TI  - Coordinating the UN System: lessons from UNAIDS: a commentary on Mackey.

PMID- 23116986
TI  - Cost-effectiveness at two years in the VA Open Versus Endovascular Repair Trial.
AB  - BACKGROUND: Long-term clinical outcomes have been similar for endovascular and
      open repair of abdominal aortic aneurysm (AAA), increasing the importance of
      comparing cost-effectiveness. METHODS: We compared data to two years from a
      multicenter randomized trial of 881 patients. Quality-adjusted life years (QALYs)
      were calculated from EQ-5D questionnaires. Healthcare utilization data were
      obtained from patients and from national VA and Medicare sources. VA costs were
      obtained using methods previously developed by the VA Health Economics Resource
      Center. Costs for non-VA care were determined from Medicare or billing data.
      RESULTS: Mean life-years were 1.78 in the endovascular and 1.74 in the open
      repair group (P = 0.29), and mean QALYs were 1.462 in the endovascular and 1.461
      in the open group (P = 0.78). Although graft costs were higher in the
      endovascular group ($14,052 vs. $1363; P < 0.001), length of stay was shorter
      (5.0 vs. 10.5 days; P < 0.001), resulting in lower cost of AAA repair
      hospitalization in the endovascular group ($37,068 vs. $42,970; P = 0.04). Costs
      remained lower after 2 years in the endovascular group but the difference was no
      longer significant (-$5019; 95% CI: -$16,720 to $4928; P = 0.35). The probability
      that endovascular repair was both more effective and less costly was 70.9% for
      life-years and 51.4% for QALYs. INTERPRETATION: Endovascular repair is a cost
      effective alternative to open repair in the US VA healthcare system for at least
      the first two years.

PMID- 23116993
TI  - A United Nations Global Health Panel for Global Health Governance: a commentary
      on Mackey.

PMID- 23116994
TI  - Carcinogenicity assessments: WHO decides?

PMID- 23116995
TI  - The limitations of imaging response criteria.

PMID- 23116996
TI  - Improving outcomes for elderly patients with AML.

PMID- 23116997
TI  - Treatment of breast cancer during pregnancy.

PMID- 23116998
TI  - Treatment options in elderly patients with glioblastoma.

PMID- 23117000
TI  - HIPEC: standard of care or an experimental approach?

PMID- 23117001
TI  - Conditional survival of patients with metastatic renal-cell carcinoma.

PMID- 23117002
TI  - Management of colon cancer: resource-stratified guidelines from the Asian
      Oncology Summit 2012.
AB  - Colon cancer is seen with increasing frequency in the Asia-Pacific region, and it
      is one of the most important causes of cancer mortality worldwide. This article
      reviews the available evidence for optimum management of colon cancer-in
      particular, with respect to screening and early detection of colon cancer,
      laparoscopic surgical treatment, adjuvant treatment of individuals with high-risk
      stage II and stage III cancer, palliative treatment of patients with metastatic
      disease, and management of resectable and potentially resectable metastases-and
      how these strategies can be applied in Asian countries with different levels of
      health-care resources and economic development, stratified by basic, limited,
      enhanced, and maximum resource levels.

PMID- 23117003
TI  - Management of kidney cancer in Asia: resource-stratified guidelines from the
      Asian Oncology Summit 2012.
AB  - Treatment of renal-cell carcinoma has progressed over the past decade, in terms
      of surgical and systemic therapy. Current treatment guidelines are based on
      clinical evidence, but do not take into account resource limitations among
      different countries. These limitations, which include financial and logistical
      challenges and lack of skilled health-care professionals, have the greatest
      effect in low-income countries. This consolidated statement gives treatment
      recommendations for renal-cell carcinoma that are based on clinical evidence and
      stratified according to extent of resource availability. The statement was
      formulated by a panel of urologists, medical oncologists, and clinical
      oncologists from Asian countries, at a consensus session on kidney cancer that
      was held as part of the 2012 Asian Oncology Summit in Singapore. Resource levels
      are defined according to a four-tier system (basic, limited, enhanced, and
      maximum), and treatment recommendations are specified based on availability of
      financial, skill, and logistical resources.

PMID- 23117004
TI  - Supportive, palliative, and end-of-life care for patients with cancer in Asia:
      resource-stratified guidelines from the Asian Oncology Summit 2012.
AB  - The burden of cancer in Asia is high; 6.1 million new cases were diagnosed in the
      continent in 2008, which accounted for 48% of new cases worldwide. Deaths from
      cancer are expected to continue to rise because of ageing populations and
      modifiable risk factors such as tobacco and alcohol use, diet, and obesity. Most
      patients who are diagnosed with cancer in Asia have advanced disease that is not
      amenable to curative treatment, which means that they are likely to have pain and
      other symptoms and psychosocial concerns. These burdens vary with the economic
      and political situation of the different countries and are affected by such
      factors as an absence of screening programmes, insufficient cancer diagnostic and
      treatment services (especially in sparsely populated and rural areas), legal
      restrictions on access to drugs to relieve pain, and a medical culture in which
      quality-of-life considerations are undervalued in relation to imperatives to
      treat. These issues could be ameliorated by increased investment in cancer
      screening, removal of restrictions on prescription of opioids, and improvements
      in medical education to increase recognition of treatment futility. Supportive,
      palliative, and end-of-life care offer the potential to enhance quality of life,
      improve pain control, and reduce suffering for patients with cancer and their
      families, and to give patients a dignified death. All patients should have access
      to such care-in resource-rich regions these services should be integrated into
      oncology services, whereas in resource-poor regions they should be the main focus
      of treatment. The form of care should depend on the economic circumstances within
      and across countries, and recommendations are made across four resource
      classifications (basic to maximal) to take account of the diversity of settings
      in Asia.

PMID- 23117005
TI  - Do low-grade and low-volume prostate cancers bear the hallmarks of malignancy?
AB  - Prostate cancer is generally multifocal and consists of a dominant focus-measured
      by tumour volume and deemed the index lesion-and one or more separate, secondary
      tumour foci of smaller volume. Much laboratory and clinical evidence has shown
      that we need to rethink how we regard low-grade and low-volume prostate lesions.
      In this Personal View, we discuss why small, low-grade Gleason pattern prostate
      lesions, which are currently designated as prostate cancer, could be regarded as
      non-malignant. These lesions either do not meet the criteria of the hallmarks of
      cancer or robust evidence that they do so is absent, by contrast with large
      lesions with a high Gleason grade, which seem to cause most metastatic disease.

PMID- 23117006
TI  - Acetylcholinesterase and agrin: different functions, similar expression patterns,
      multiple roles.
AB  - Acetylcholinesterase (AChE) and agrin play unique functional roles in the
      neuromuscular junction (NMJ). AChE is a cholinergic and agrin a synaptogenetic
      component. In spite of their different functions, they share several common
      features: their targeting is determined by alternative splicing; unlike most
      other NMJ components they are expressed in both, muscle and motor neuron and both
      reside on the synaptic basal lamina of the NMJ. Also, both were reported to play
      various nonjunctional roles. However, while the origin of basal lamina bound
      agrin is undoubtedly neural, the neural origin of AChE, which is anchored to the
      basal lamina with collagenic tail ColQ, is elusive. Hypothesizing that motor
      neuron proteins targeted to the NMJ basal lamina share common temporal pattern of
      expression, which is coordinated with the formation of basal lamina, we compared
      expression of agrin isoforms with the expression of AChE-T and ColQ in the
      developing rat spinal cord at the stages before and after the formation of NMJ
      basal lamina. Cellular origin of AChE-T and agrin was determined by in situ
      hybridization and their quantitative levels by RT PCR. We found parallel increase
      in expression of the synaptogenetic (agrin 8) isoform of agrin and ColQ after the
      formation of basal lamina supporting the view that ColQ bound AChE and agrin 8
      isoform are destined to the basal lamina. Catalytic AChE-T subunit and agrin
      isoforms 19 and 0 followed different expression patterns. In accordance with the
      reports of other authors, our investigations also revealed various alternative
      functions for AChE and agrin. We have already demonstrated participation of AChE
      in myoblast apoptosis; here we present the evidence that agrin promotes the
      maturation of heavy myosin chains and the excitation-contraction coupling. These
      results show that common features of AChE and agrin extend to their capacity to
      play multiple roles in muscle development.

PMID- 23117007
TI  - Curative surgery for locally advanced retroperitoneal mature teratoma in an
      adult. Case report.
AB  - INTRODUCTION: Primary teratomas of retroperitoneum are not usual in the adult
      population. These tumors most commonly seen at the gonadal and sacrococcygeal
      regions. Herein we describe a case of an 18-year-old female who had a benign
      cystic teratoma at the retroperitoneum. PRESENTATION OF CASE: The patient
      underwent an operation at another hospital following a misdiagnosis of hydatid
      cyst. The patient was referred to our hospital because of the detection of an
      unresectable tumor during her operation. A computerized tomography (CT)
      angiography revealed a cystic mass, with a diameter of 14cm which was invaded
      into the retrohepatic suprarenal inferior vena cava and also extended to the
      posterior aspect of the liver. Additionally the mass invaded the posterior wall
      of the inferior vena cava and the right renal vein. The tumor was completely
      resected with a vascular resection. The inferior vena cava was reconstructed with
      a 12cm Dacron((r)) graft and the renal vein was implanted. The patient's
      postoperative period was uneventful. DISCUSSION: Germ cell tumors of
      retroperitoneum are usually seen in children, but there are also some reports of
      adult cases in the literature. Adult cases are especially seen in females.
      Imaging studies are paramount for diagnosis, preoperative strategy and safe
      surgical excision. CT scans and MRIs can identify various components of these
      tumors. CONCLUSION: Even though primary retroperitoneal teratomas are quite rare
      in adults. Preoperative radiology imaging and strategy is critical for performing
      a safe surgery. The gold standard treatment strategy for this neoplasm is the
      surgical resection.

PMID- 23117008
TI  - The value of a rate change in determining the tachycardia mechanism: which
      circuits are involved?

PMID- 23117010
TI  - Expanding medicinal chemistry space.
AB  - Clinically useful drugs target a relatively small number of proteins that lie
      within a clearly defined and chemically accessible space. However, many high
      value biological targets lie outside this chemical space, and an ability to
      access such 'intractable' targets not amenable to traditional small molecule
      intervention would expand treatment options and be a major boost for patients and
      the pharmaceutical industry. To date, success has been limited but new
      technologies and approaches are beginning to emerge that could provide novel lead
      generation capabilities that enable access to new drug target classes. We review
      these new approaches and their ability to provide the novel leads needed to
      tackle a new generation of biological targets.

PMID- 23117009
TI  - Current status of renal denervation in resistant hypertension.
AB  - Resistant hypertension is a frequent form of arterial hypertension that, with the
      exception of malignant hypertension, constitutes the most dangerous stage of
      arterial hypertension. Recently we have improved the detection, diagnosis, and
      therapy of resistant hypertensives. The technique of renal denervation with a
      catheter has improved the control of blood pressure in such patients. The
      technique is simple, safe, and available data indicates that it is effective.
      More data and longer follow-up of patients are required to promote wide
      acceptance of this new technique.

PMID- 23117011
TI  - Reconstituted high-density lipoprotein attenuates atherogenesis partly by
      regulating HSP27 in hyperlipidemic apoE-/- mice.

PMID- 23117012
TI  - Identifying patients for early discharge: performance of decision rules among
      patients with acute chest pain.
AB  - BACKGROUND: The HEART score and North American Chest Pain Rule (NACPR) are
      decision rules designed to identify acute chest pain patients for early discharge
      without stress testing or cardiac imaging. This study compares the clinical
      utility of these decision rules combined with serial troponin determinations.
      METHODS AND RESULTS: A secondary analysis was conducted of 1005 participants in
      the Myeloperoxidase In the Diagnosis of Acute coronary syndromes Study (MIDAS).
      MIDAS is a prospective observational cohort of Emergency Department (ED) patients
      enrolled from 18 US sites with symptoms suggestive of acute coronary syndrome
      (ACS). The ability to identify participants for early discharge and the
      sensitivity for ACS at 30 days were compared among an unstructured assessment,
      NACPR, and HEART score, each combined with troponin measures at 0 and 3h. ACS,
      defined as cardiac death, acute myocardial infarction, or unstable angina,
      occurred in 22% of the cohort. The unstructured assessment identified 13.5% (95%
      CI 11.5-16%) of participants for early discharge with 98% (95% CI 95-99%)
      sensitivity for ACS. The NACPR identified 4.4% (95% CI 3-6%) for early discharge
      with 100% (95% CI 98-100%) sensitivity for ACS. The HEART score identified 20%
      (95% CI 18-23%) for early discharge with 99% (95% CI 97-100%) sensitivity for
      ACS. The HEART score had a net reclassification improvement of 10% (95% CI 8-12%)
      versus unstructured assessment and 19% (95% CI 17-21%) versus NACPR. CONCLUSIONS:
      The HEART score with 0 and 3 hour serial troponin measures identifies a
      substantial number of patients for early discharge while maintaining high
      sensitivity for ACS.

PMID- 23117014
TI  - Patients are not consumers and doctors are not providers.

PMID- 23117013
TI  - Ongoing treatment with non-steroidal anti-inflammatory drugs at time of admission
      is associated with poorer prognosis in patients with first-time acute myocardial
      infarction.
AB  - BACKGROUND: Use of non-steroidal anti-inflammatory drugs (NSAIDs) has been
      associated with increased cardiovascular morbidity and mortality. The purpose of
      this study was to examine the effect of ongoing NSAID treatment at time of
      admission for myocardial infarction (MI) on prognosis. METHODS: All patients
      admitted with first-time MI in 1997-2006 were included by use of individual-level
      linkage of nationwide registries. By claimed prescription of NSAIDs, availability
      of tablets was estimated within 14 days prior to inclusion and defined ongoing
      use. Risk of death within 30 days and risk of death or MI within 1 year was
      analyzed by logistic regression and Cox proportional-hazard models, respectively.
      RESULTS: A total of 97,458 patients were included (mean age 69.9 [SD 13.2] years
      and 62% males); the 30 day and 1 year mortality rates were 18.1% and 27.7%,
      respectively. Ongoing NSAID treatment was identified in 12,156 (12.5%) patients
      and 30-day mortality was significantly increased in patients receiving rofecoxib
      (odds ratio [OR] 1.43; 95% confidence interval [CI] 1.22-1.68) and celecoxib (OR
      1.23; CI 1.03-1.47) relative to no use of NSAIDs. Correspondingly, the 1-year
      rate of death or recurrent MI was significantly increased in patients receiving
      rofecoxib (hazard ratio [HR] 1.15; CI 1.04-1.27), celecoxib (HR 1.13; CI 1.01
      1.26), diclofenac (HR 1.12; CI 1.04-1.20) or any NSAID use (HR 1.05; CI 1.02
      1.09). No association was found for naproxen or ibuprofen. CONCLUSION: Ongoing
      treatment with NSAIDs and in particular the cyclooxygenase-2-selective inhibitors
      rofecoxib, celecoxib, and diclofenac is associated with worsened prognosis in
      patients admitted with first-time MI.

PMID- 23117015
TI  - Comparison of two treadmill training programs on walking ability and endothelial
      function in intermittent claudication.
AB  - BACKGROUND: In this randomized trial we compared two treadmill trainings, based
      on exercises performed to moderate claudication pain vs pain-free training, with
      respect to their effects on walking ability and endothelial function. METHODS: A
      total of sixty patients with stable intermittent claudication were randomized to
      the pain-free treadmill training (repetitive intervals to onset of claudication
      pain) or moderate treadmill training (repetitive intervals to moderate
      claudication pain). In both groups exercises were performed 3 times a week for 3
      months. Changes in flow mediated dilatation (FMD) and treadmill walking
      performance as well as plasma levels of C-reactive protein (hs-CRP) and
      fibrinogen were assessed before and after the program. RESULTS: Fifty-two
      patients completed the training program. Post-training maximal walking time was
      prolonged by 100% (p<0.001) vs 98% (p<0.001), and pain-free walking time by 120%
      (p<0.001) vs 93% (p<0.001) in the moderate training group as compared to the pain
      free training group, respectively. FMD increased by 56% (p<0.001) in the moderate
      training group and by 36% (p<0.01) in the pain-free training group. No
      significant changes in the levels of hs-CRP and fibrinogen were seen after
      treadmill program in either group. CONCLUSIONS: Both pain-free treadmill training
      and the moderate treadmill training have similar efficacy on walking ability in
      patients with claudication. The improvement of post-training FMD indicates
      systemic effect of both treadmill programs on endothelial function. Both programs
      appear to be safe therapeutic modes, since none of them escalates the
      inflammation. Pain-free treadmill training seems useful and effective therapeutic
      option for patients with claudication.

PMID- 23117016
TI  - Troponin T is a strong marker of mortality in hospitalized patients.
AB  - BACKGROUND: Cardiac troponins are diagnostic markers in acute coronary syndrome
      and prognostic markers in stable coronary disease. Small increases are
      occasionally observed in patients with non-cardiac disease, but the prevalence
      and prognostic value of increased troponin in the general hospitalized population
      are unknown. METHODS: Consecutive patients aged >40 years admitted to a district
      hospital between 1 April 1998 and 31 March 1999 were included. A comprehensive
      medical interview and clinical examination were performed including
      echocardiography and measurement of natriuretic peptides and troponin T with a
      high-sensitivity assay (hs-TnT). RESULTS: Serum for analyses of hs-TnT was
      available from 1176 patients. Patients were 73.7 years old on average
      (interquartile range, 64.5-80.0 years), 59.2% were women and median follow-up was
      11.4 years. The prevalence of elevated hs-TnT (> 99(th) percentile) was 57.1% of
      the entire cohort and 52.3% of patients with non-cardiac diagnoses. hs-TnT above
      the median (17 ng/L) was associated in univariate analysis with a 3-fold higher
      mortality in the entire population (multivariate hazard rate (HR) from 1.3 to 1.8
      for 1 and 11 year mortality, respectively). In patients without past or present
      ischemic heart disease hs-TnT in the upper quartile (above 34.8 ng/L) was
      associated in univariate analysis with a 5-fold higher mortality risk
      (multivariable HR 1.8 to 2.2 for 1 and 11 year mortality, respectively).
      CONCLUSION: More than half of the hospitalized patients had hs-TnT levels above
      the 99(th) percentile. Elevated hs-TnT is a strong mortality risk marker in
      general hospitalized older patients.

PMID- 23117017
TI  - Cardiac auscultation: preliminary findings of a pilot study using continuous Wave
      Doppler and comparison with classic auscultation.

PMID- 23117018
TI  - Complications of lymphadenectomy for gynecologic cancer.
AB  - INTRODUCTION: Symptomatic postoperative lymphocysts (SPOLs) and lower-limb
      lymphedema (LLL) are probably underestimated complications of lymphadenectomy for
      gynecologic malignancies. Here, our objective was to evaluate the incidence and
      risk factors of SPOLs and LLL after pelvic and/or aortocaval lymphadenectomy for
      gynecologic malignancies. METHODS: Single-center retrospective study of
      consecutive patients who underwent pelvic and/or aortocaval lymphadenectomy for
      ovarian cancer, endometrial cancer, or cervical cancer between January 2007 and
      November 2008. The incidences of SPOL and LLL were computed with their 95%
      confidence intervals (95%CIs). Multivariate logistic regression was performed to
      identify independent risk factors for SPOL and LLL. RESULTS: We identified 88
      patients including 36 with ovarian cancer, 35 with endometrial cancer, and 17
      with cervical cancer. The overall incidence of SPOL was 34.5% (95%CI, 25-45) and
      that of LLL was 11.4% (95% confidence interval [95%CI], 5-18). Endometrial cancer
      was independently associated with a lower risk of SPOL (adjusted odds ratio
      [aOR], 0.09; 95%CI, 0.02-0.44) and one or more positive pelvic nodes with a
      higher risk of SPOL (aOR, 4.4; 95%CI, 1.2-16.3). Multivariate logistic regression
      failed to identify factors significantly associated with LLL. CONCLUSION:
      Complications of lymphadenectomy for gynecologic malignancies are common. This
      finding supports a more restrictive use of lymphadenectomy or the use of less
      invasive techniques such as sentinel node biopsy.

PMID- 23117019
TI  - A ROS rheostat for cell fate regulation.
AB  - Cellular reactive oxygen species (ROS) are tightly regulated to prevent tissue
      damage. ROS also help to monitor different cell fates, suggesting that a 'ROS
      rheostat' exists in cells. It is well established that ROS are crucial for stem
      cell biology; in this review, we discuss how mitochondrial ROS influence
      hematopoietic cell fates. We also examine the importance in this process of BID
      and other BCL-2 family members, many of which have been implicated in regulating
      cell fates by modulating mitochondrial integrity/activity and cell cycle
      progression in the hematopoietic lineage. Based on this knowledge, we propose
      that selected BCL-2 proteins coordinate mitochondria and nuclear activities via
      ROS to enable 'synchronized' cell fate decisions.

PMID- 23117020
TI  - Discrimination of squamous cell carcinoma in situ from seborrheic keratosis by
      color analysis techniques requires information from scale, scale-crust and
      surrounding areas in dermoscopy images.
AB  - Scale-crust, also termed "keratin crust", appears as yellowish-to-tan scale on
      the skin's surface. It is caused by hyperkeratosis and parakeratosis in inflamed
      areas of squamous cell carcinoma in situ (SCCIS, Bowen's disease) and is a
      critical dermoscopy feature for detecting this skin cancer. In contrast, scale
      appears as a white-to-ivory detaching layer of the skin, without crust, and is
      most commonly seen in benign lesions such as seborrheic keratoses (SK).
      Distinguishing scale-crust from ordinary scale in digital dermoscopy images holds
      promise for early SCCIS detection and differentiation from SK. Reported here are
      image analysis techniques that best characterize scale-crust in SCCIS and scale
      in SK, thereby allowing accurate separation of these two dermoscopic features.
      Classification using a logistic regression operating on color features extracted
      from these digital dermoscopy structures can reliably separate SCCIS from SK.

PMID- 23117021
TI  - Quillaja saponaria extract as mucosal adjuvant with chitosan functionalized gold
      nanoparticles for mucosal vaccine delivery: stability and immunoefficiency
      studies.
AB  - Carrier mediated delivery of vaccines along with adjuvants can possibly address
      the issue related to oral vaccines like inadequate immune potentiation. In this
      study, chitosan functionalized gold nanoparticles (CsAuNPs) were used as a
      carrier for the model antigen tetanus toxoid (TT) along with immunostimulant
      Quillaja saponaria extract (QS). Physicochemical properties (size, zeta
      potential, pH value) of formulation were investigated as stability indicating
      parameters. The synthesized CsAuNPs were spherical in shape, around 40 nm in
      size, positively charged (around +35 mV) and had TT and QS payload of 65% and
      0.01%, respectively. Formulation parameters did not alter the secondary structure
      of TT, as determined by FTIR, fluorescence and CD spectroscopy. Antigen
      specificity, determined by an ELISA, was also not compromised. The CsAuNPs
      conferred protection to TT against gastric hydrolysis as studied in vitro. TT-QS
      CsAuNPs induced up to 28-fold immune responses compared to control formulations
      (TT, TT-QS) after oral administration of formulations in BALB/c mice. The immune
      responses were quantified by measuring the TT-specific IgG and IgA titers using
      ELISA. Findings herein demonstrate that co-delivery of TT and QS with
      functionalized CsAuNPs promotes better systemic and local immune responses and
      hence can be considered as a sound approach for oral vaccine delivery.

PMID- 23117023
TI  - Development of a percutaneous penetration predictive model by SR-FTIR.
AB  - This work focused on developing a new evaluation criterion of percutaneous
      penetration, in complement to Log Pow and MW and based on high spatial resolution
      Fourier transformed infrared (FTIR) microspectroscopy with a synchrotron source
      (SR-FTIR). Classic Franz cell experiments were run and after 22 h molecule
      distribution in skin was determined either by HPLC or by SR-FTIR. HPLC data
      served as reference. HPLC and SR-FTIR results were compared and a new predictive
      criterion based from SR-FTIR results, named S(index), was determined using a
      multi-block data analysis technique (ComDim). A predictive cartography of the
      distribution of molecules in the skin was built and compared to OECD predictive
      cartography. This new criterion S(index) and the cartography using SR-FTIR/HPLC
      results provides relevant information for risk analysis regarding prediction of
      percutaneous penetration and could be used to build a new mathematical model.

PMID- 23117024
TI  - Glycyrrhetinic acid-graft-hyaluronic acid conjugate as a carrier for synergistic
      targeted delivery of antitumor drugs.
AB  - Glycyrrhetinic acid-graft-hyaluronic acid (HGA) conjugate was synthesized as a
      carrier for intravenous administration of paclitaxel (PTX), which combined
      hyaluronic acid (HA) and glycyrrhetinic acid (GA) as the active targeting ligands
      to liver tumor. In the present study, physicochemical characteristics, cellular
      uptake efficiency, and in vivo fates of HGA conjugates were investigated. HGA
      nanoparticles could readily load PTX with high efficiency up to 31.16 wt.% and
      entrapment efficiency to 92.02%. Moreover, PTX-loaded HGA nanoparticles exhibited
      more significant cytotoxicity to HepG2 cells than B16F10 cells due to
      simultaneously over-expressing HA and GA receptors. Meanwhile, the cellular
      uptake of nanoparticles was clearly enhanced in HepG2 and B16F10 cells compared
      to a normal fibroblast cell (HELF cells). In particular, more HGA nanoparticles
      were taken up by HepG2 cells than by B16F10 cells, which might be attributed to
      the affinity of multiple ligands of HA and GA to HepG2 cells. Furthermore, liver
      and tumor targeting activity of HGA nanoparticles was also confirmed by in vivo
      imaging analysis. The fluorescence signals of DiR-labeled HGA nanoparticles in
      tumor and liver were 2.88 and 1.83 folds stronger than that of the control,
      respectively. These results indicate HGA nanoparticles can be a potential drug
      carrier with "double target sites" for liver cancer therapy.

PMID- 23117022
TI  - Recent advances in drug eluting stents.
AB  - One of the most common medical interventions to reopen an occluded vessel is the
      implantation of a coronary stent. While this method of treatment is effective
      initially, restenosis, or the re-narrowing of the artery frequently occurs
      largely due to neointimal hyperplasia of smooth muscle cells. Drug eluting stents
      were developed in order to provide local, site-specific, controlled release of
      drugs that can inhibit neointima formation. By implementing a controlled release
      delivery system it may be possible to control the time release of the
      pharmacological factors and thus be able to bypass some of the critical events
      associated with stent hyperplasia and prevent the need for subsequent
      intervention. However, since the advent of first-generation drug eluting stents,
      long-term adverse effects have raised concerns regarding their safety. These
      limitations in safety and efficacy have triggered considerable research in
      developing biodegradable stents and more potent drug delivery systems. In this
      review, we shed light on the current state-of-the-art in drug eluting stents,
      problems related to them and highlight some of the ongoing research in this area.

PMID- 23117025
TI  - In line monitoring of the preparation of water-in-oil-in-water (W/O/W) type
      multiple emulsions via dielectric spectroscopy.
AB  - Multiple emulsions offer various applications in a wide range of fields such as
      pharmaceutical, cosmetics and food technology. Two features are known to yield a
      great influence on multiple emulsion quality and utility as encapsulation
      efficiency and prolonged stability. To achieve a prolonged stability, the
      production of the emulsions has to be observed and controlled, preferably in
      line. In line measurements provide available parameters in a short time frame
      without the need for the sample to be removed from the process stream, thereby
      enabling continuous process control. In this study, information about the
      physical state of multiple emulsions obtained from dielectric spectroscopy (DS)
      is evaluated for this purpose. Results from dielectric measurements performed in
      line during the production cycle are compared to theoretically expected results
      and to well established off line measurements. Thus, a first step to include the
      production of multiple emulsions into the process analytical technology (PAT)
      guidelines of the Food and Drug Administration (FDA) is achieved. DS proved to be
      beneficial in determining the crucial stopping criterion, which is essential in
      the production of multiple emulsions. The stopping of the process at a less-than
      ideal point can severely lower the encapsulation efficiency and the stability,
      thereby lowering the quality of the emulsion. DS is also expected to provide
      further information about the multiple emulsion like encapsulation efficiency.

PMID- 23117026
TI  - Oxytocin differentially modulates eye gaze to naturalistic social signals of
      happiness and anger.
AB  - A number of previous studies has shown that oxytocin (OT) promotes facial emotion
      recognition and enhances eye gaze to facial stimuli in humans. Other studies
      report valence-specific effects of OT, supporting the proposed prosocial role of
      OT in social interactions. In the present study, we tested the hypothesis whether
      OT might selectively enhance eye gaze to positive, approach-related, but not to
      negative, threat-related social cues. In a placebo-controlled, double-blind,
      between-subject design, we assessed the effects of intranasal OT administration
      (24 IU) in 62 healthy male volunteers on eye gaze toward the eyes of neutral,
      positive (happy) and negative (angry) facial expressions compared with placebo.
      In order to capture the dynamics of facial expressions, we used video sequences
      showing neutral faces gradually displaying a specific emotion. In line with
      previous studies, OT increased eye gaze toward neutral facial expressions.
      Moreover, under OT treatment, eye gaze remained increased when the face showed a
      happy facial expression, but in contrast decreased when the face displayed an
      angry expression. These results support the notion that OT differentially
      modulates visual attention toward social signals of positive approach and threat
      and thereby contributes to the modulation of non-verbal interpersonal
      communication.

PMID- 23117027
TI  - Science, truth, and forensic cultures: the exceptional legal status of DNA
      evidence.
AB  - Many epistemological terms, such as investigation, inquiry, argument, evidence,
      and fact were established in law well before being associated with science.
      However, while legal proof remained qualified by standards of 'moral certainty',
      scientific proof attained a reputation for objectivity. Although most forms of
      legal evidence (including expert evidence) continue to be treated as fallible
      'opinions' rather than objective 'facts', forensic DNA evidence increasingly is
      being granted an exceptional factual status. It did not always enjoy such status.
      Two decades ago, the scientific status of forensic DNA evidence was challenged in
      the scientific literature and in courts of law, but by the late 1990s it was
      being granted exceptional legal status. This paper reviews the ascendancy of DNA
      profiling, and argues that its widely-heralded objective status is bound up with
      systems of administrative accountability. The 'administrative objectivity' of DNA
      evidence rests upon observable and reportable bureaucratic rules, records,
      recording devices, protocols, and architectural arrangements. By highlighting
      administrative sources of objectivity, this paper suggests that DNA evidence
      remains bound within the context of ordinary organisational and practical
      routines, and is not a transcendent source of 'truth' in the criminal justice
      system.

PMID- 23117028
TI  - Quorum-sensing signal disperses bacteria from biofilms.

PMID- 23117029
TI  - Expression of sfrp1 and activation of the Wnt pathway in the adrenal glands of
      healthy ferrets and neutered ferrets with hyperadrenocorticism.
AB  - Gonadectomy induces the pathogenesis of luteinising hormone receptor positive,
      androgen and oestrogen producing tumours in the adrenal cortex of ferrets. In
      mice, the castration-dependent appearance of adrenocortical tumours has been
      attributed to loss of expression of the tumour suppressor gene Secreted Frizzled
      Related Protein 1 (sfrp1), a dominant inhibitor of the Wnt pathway, which
      controls cell proliferation and 'cell faith' decisions. This study investigated
      whether sfrp1 and the Wnt pathway play a similar role in the pathogenesis of
      hyperadrenocorticism in ferrets. The expression of sfrp1 and three target genes
      of the Wnt pathway (c-myc, axin2 and cyclinD1) in seven adrenal glands from
      healthy ferrets and in 13 adrenocortical tumours were studied by quantitative
      real-time PCR. Nuclear beta-catenin staining was assessed by
      immunohistochemistry. Sfrp1 mRNA expression was up-regulated and axin2 and
      cyclinD1 were down-regulated in the tumour group in comparison with the control
      group. Decreased nuclear beta-catenin staining supported the decrease in active
      Wnt signalling in adrenocortical tumours in ferrets. Therefore, it is unlikely
      that the involvement of sfrp1 and the Wnt pathway in the pathogenesis of
      adrenocortical tumours in ferrets is similar to that described in mice.

PMID- 23117030
TI  - Weight loss resistance: a further consideration for the nutritional management of
      obese Equidae.
AB  - Evidence-based, weight loss management advice is required to address equine
      obesity. Changes in body mass (BM), body condition score (BCS), heart (HG) and
      belly circumference (BG), direct (ultrasonographic) and indirect (D(2)O dilution,
      bioelectrical impedance analysis [BIA]) measures of body fat as well as indices
      of insulin resistance (IR) were monitored in 12 overweight (BCS >= 7/9) horses
      and ponies of mixed breed and gender for 16 weeks. Animals were randomly assigned
      to two groups (Group 1, n=6, BCS 7.6/9 +/- 0.6, 489 +/- 184.6 kg; Group 2, n=6,
      BCS 8.1/9 +/- 0.6, 479 +/- 191.5 kg). Daily dry matter intake (DMI) was
      restricted to 1.25% BM as one of two, near-isocaloric (DE ~0.115 MJ/kg BM/day),
      forage-based diets (Group 1, 0.8% BM chaff-based feed: 0.45% BM hay; Group 2,
      1.15% BM hay: 0.1% BM nutrient-balancer). Statistical modelling revealed
      considerable between-animal heterogeneity in proportional weight losses (0.16
      0.55% of Week 1 BM weekly). The magnitude of weight loss resistance (WLR) or
      sensitivity to dietary restriction was independent of diet or any measured outset
      variable and was largely (65%) attributed to animal identity. Predicted rates of
      weight loss decreased over time. BCS and BIA were poor estimates of D(2)O-derived
      body fat%. Reciprocal changes in depths of retroperitoneal and subcutaneous
      adipose tissues were evident. Changes in BG were associated with losses in
      retroperitoneal fat and BM (r(2), 0.67 and 0.79). Indices of IR improved for 9/12
      animals by Week 16. For obese animals, weight loss should be initiated by
      restricting forage DMI to 1.25% BM. Subsequent restriction to 1% BM may be
      warranted for WLR animals.

PMID- 23117031
TI  - Histological behaviour of zirconia implants: an experiment in rats.
AB  - New biomaterials including surface modifications should undergo in vitro and in
      vivo evaluation before clinical trials. The objective of our in vivo study was to
      evaluate the biocompatibility of one of the newly fabricated zirconia implant
      surfaces, called "mds". For this purpose, the osseointegration of these implants
      was analyzed after implantation in surgically created defects in the cranium of
      adult male rats. After a healing period of 28 and 56 days, respectively, bone
      tissue specimens containing the implants were processed and histologically
      analyzed. For this purpose, sections were stained with haematoxylin/eosin and
      Masson Goldner trichrome. No signs of cellular inflammatory infiltrate were found
      in any of the animals. After 28 days, slices showed pronounced development of
      blood vessels and bone regeneration. After 56 days of healing, direct bridging of
      the bone defects was detectable with distinctly visible kit lines. There were
      cell rich areas of connective tissue/bone marrow between zirconia discs and
      bearing bone. Histomorphometric analysis presented a regenerated bone mean value
      of 36.3% after 28 days of healing. After 56 days of healing, a 1.6 fold increased
      bone mean value was observed (58.2%). Using the same analysis, 1% and 39.9% of
      bone-implant-contact was visible after both healing periods, respectively. On
      average, connective tissue/marrow spaces occupied 99% of implant-contact-area
      after 28 days of healing. This area was reduced to 60.1% after 56 days. Within
      the limits of the animal investigation presented, it was concluded that the
      tested surface modification of zirconia implants were biocompatible and
      osseoconductive.

PMID- 23117032
TI  - Identification of hemoglobin variants in samples received for glycated hemoglobin
      testing.
AB  - BACKGROUND: In 2010 Singapore's National Health Survey reported 11.3% of the
      population between 18-69 years of age with diabetes, compared to 8.2% in 2006.
      This increasing trend reinforces the dependence on HbA(1c) for management of
      glycemic control. METHODS: To determine the incidence of hemoglobin variants
      received from our diabetic population who are attending the National University
      Hospital for testing of their HbA(1c) and determine whether the hemoglobin
      variant caused an interpretation issue, we reviewed all chromatograms from
      patients sending a sample for HbA(1c) analysis for a three-month period. Analysis
      was performed on the Variant II using the HbA(2)/HbA(1c) Dual program. RESULTS:
      Our sub-analysis identified 2 cases of alpha thalassemia, 2 cases of beta
      thalassemia; 5 cases of hemoglobin E variant homozygous, 1 case of hemoglobin J
      variant, 110 cases of hemoglobin E, 7 cases of hemoglobin S, 1 case of hemoglobin
      C and 1 case of hemoglobin D, all heterozygous. HbA(1c) results could be
      confidently reported in all cases except the homozygote variant and the
      hemoglobin J variant. CONCLUSIONS: Overall we obtained a prevalence of 2.3% of
      hemoglobin variants in our diabetic population being screened by HbA(1c) using
      Variant II.

PMID- 23117033
TI  - Significantly increased concentration of soluble urokinase-type plasminogen
      activator receptor in the blood of patients with pelvic inflammatory disease.
AB  - BACKGROUND: To determine expression levels of urokinase-type plasminogen
      activator (uPA), soluble urokinase-type plasminogen activator receptor (suPAR),
      plasminogen activator inhibitor-1 (PAI-1) in plasma and to identify gene
      polymorphisms specific to patients with pelvic inflammatory disease (PID) and
      healthy controls. METHODS: Enzyme-linked immunosorbent assay and polymerase chain
      reaction-restriction fragment length polymorphism were used to measure plasma
      levels and polymorphisms in uPA, suPAR, and PAI-1 among seventy healthy controls
      and 64 PID patients before and after they received routine treatment protocols.
      RESULTS: The levels of plasma uPA (ng/ml) and soluble suPAR (pg/ml) were
      significantly increased in PID patients (uPA: 0.57+/-0.03; suPAR: 1372.04+/
      68.20) when compared to that in normal controls (uPA: 0.55+/-0.06, p=0.002;
      suPAR: 1192.46+/-51.98, p=0.04); moreover, suPAR decreased significantly after
      treatment when compared to levels noted in the same patients (1220.06+/-58.14;
      p=0.003) after they received treatment. The increased expression of suPAR was
      significantly correlated with WBC counts (r=0.382, p=0.002, n=64) in blood as
      well as the plasma levels of CRP (r=0.441, p<0.0001, n=64) and uPA (r=0.426,
      p<0.0001, n=64) of PID patients prior to receiving treatment. CONCLUSIONS:
      Increased plasma suPAR could be a biological marker for the diagnosis of PID and
      may reflect a new focus in targeted therapy for pelvic inflammatory disease.

PMID- 23117034
TI  - Article downloads and citations: is there any relationship?

PMID- 23117035
TI  - Random variation and systematic error caused by various preanalytical variables,
      estimated by linear mixed-effects models.
AB  - BACKGROUND: We wanted to determine whether specific, preanalytical sample
      handling increases preanalytical variation and bias test results compared with
      optimal handling. METHODS: Blood was collected into 4 serum-separation tubes from
      each arm of 60 outpatients. In 30 of the patients, half of the tubes were
      transported in the pneumatic tube system, while the other half were manually
      delivered. In the remaining patients, the blood samples were collected using 21
      gauge straight needles (green needles) and 23-gauge butterfly needles. Half of
      the tubes were mixed by inverting 5-6 times, and the other half by one inversion.
      Linear mixed-effects models were used as statistical method. RESULTS:
      Transporting samples in the pneumatic tube system caused a significant bias to
      the results for LD (4.5 U/L, p<0.001) and magnesium (0.0021 mmol/L, p=0.003). For
      CK and glucose, the preanalytical variation was significantly higher for samples
      transported in the pneumatic tube system vs manual delivery. Using butterfly
      needles resulted in lower values (p<0.05) for calcium (-0.0072 mmol/L), CK (-0.75
      U/L) and LD (-1.6 U/L) compared with 21-gauge needles. The preanalytical
      variation for ALP was significantly higher with butterfly needles. CONCLUSIONS:
      The specific sample handling had significant but small random and systematic
      effects on results for some analytes.

PMID- 23117036
TI  - Membrane-perturbing effect of fatty acids and lysolipids.
AB  - Due to their amphipathicity fatty acids and lysolipids incorporate into lipid
      membranes and may hence exert an effect on membrane permeability, morphology, and
      stability. Several studies have shown that fatty acids and lysolipids can reduce
      the permeability barrier of model membranes. The origin of this phenomenon may be
      related to changes in the curvature stress of the membrane caused by the
      effective non-cylindrical geometry of fatty acids and lysolipids. Therefore, it
      has been proposed that the same effects may carry over to apply to the
      permeability barrier of cell membranes, in which case the effect could possibly
      be exploited to enhance intracellular drug uptake. However, fatty acids and
      lysolipids are in themselves cytotoxic in micromolar concentrations. Experiments
      with living cells have shown that fatty acids and lysolipids at concentrations
      below their cytotoxicity limit cannot render cell membranes more permeable by
      perturbing the lipid bilayer component of the membrane. We summarize the limited,
      though, conclusive, available literature on this topic. The picture that emerges
      from this discussion illustrates the importance of a lipidology-based view for
      the rational development of liposomal drug-delivery systems. It is also an
      example of possible limitations in translating knowledge from simple lipid
      bilayers to real biological membranes.

PMID- 23117037
TI  - [The use of sugammadex in end-stage renal failure with renal replacement
      therapy].

PMID- 23117038
TI  - [Magnesium sulfate in the prophylaxis of eclampsia: a retrospective study].
AB  - INTRODUCTION: The use of magnesium sulfate (MgSO(4)) has been advocated since
      2000 in France in the management of eclampsia. The aim of this study was to
      determine the frequency of use of this treatment for eclampsia in a French
      department. PATIENTS AND METHODS: All patients obstetrical patients admitted to
      Critical Care Units of Seine-Maritime for eclampsia over a period of 7 years
      (2002-2008) were included. Obstetric data, the treatment used for eclampsia and
      pre-eclampsia and maternofetal complications were collected. The primary outcome
      parameter was the use of MgSO(4) in the secondary prevention of eclampsia.
      RESULTS: Thirty-nine patients were included. Nineteen patients (48%) had
      eclampsia in prepartum, three (8%) in per-partum and 17 (44%) in post-partum
      periods. The use of MgSO(4) in the secondary prevention of eclampsia was observed
      in 92% of cases (36/39). Primary prevention was seen in 8% of cases. The duration
      of treatment was 2 days (1-7 days). The maternal and perinatal mortality was
      respectively 2.5 and 11%. CONCLUSION: In this study, the use of MgSO(4) in the
      secondary prevention is frequent. This result emphasizes the importance of the
      recommendations of learned societies in the homogenization of the management of
      rare but serious conditions such as eclampsia.

PMID- 23117039
TI  - [Postoperative pain trajectories to identify risk of chronic postsurgical pain in
      living donors for liver transplantation].
AB  - OBJECTIVES: To assess pain trajectories in predicting risk of chronic
      postoperative pain (CPP) after liver resection for living donor transplantation.
      STUDY DESIGN: Retrospective analysis of patients undergoing liver resection for
      living donor transplantation during 3years. PATIENTS AND METHODS: After recording
      perioperative data, patients presenting CPP at 3months were separated from
      patients without postsurgical pain problem in order to build a pain trajectory
      for liver donor patients without CPP. Postoperative course of liver donors with
      CPP was then compared to that standard pain trajectory. RESULTS: Sixty-five
      patients (30 females, 35 males) were included. Epidural analgesia was used in
      66%; others received autocontrolled analgesia by morphine. Severe acute pain was
      expressed by 11% and 37% at rest and movement respectively on the first day.
      Chronic pain involved six patients without any link with gender or type of
      analgesia. Analysis of pain trajectories shown that these patients presented
      either higher initial pain at day 1 or positive slopes with worsening of pain.
      CONCLUSION: Acute postoperative pain is a risk factor of developing CPP.
      Identification of those people by pain trajectories can be useful to treat them
      early.

PMID- 23117040
TI  - [Cerebral hemorrhage in a mechanically ventilated asthmatic child: multifactorial
      mechanisms].
AB  - We report the case of a 7-year-old boy with acute status asthmaticus requiring
      mechanic ventilation in the pediatric intensive care unit. He developed a brain
      hemorrhage during the course of his illness. We discuss the mechanisms that may
      have precipitated this neurological complication.

PMID- 23117041
TI  - Temporal trends in bulk milk antibodies to Salmonella, Neospora caninum, and
      Leptospira interrogans serovar hardjo in Irish dairy herds.
AB  - Bulk milk samples were collected from 309 Irish dairy herds at four time points
      during 2009 and tested for antibodies to Salmonella spp., N. caninum, and L.
      hardjo, three abortifacient agents in Irish dairy herds. Of the 312 study herds,
      49% vaccinated against Salmonella and 76% vaccinated against L. hardjo. In
      unvaccinated herds, the overall prevalence of antibody positive herds was 49% for
      Salmonella, 19% for N. caninum and 86% for L. hardjo. There was no association
      between both testing positive for and incidence of Salmonella or L. hardjo on
      sample date and calving season. A significant association was found between
      sample date and both testing positive for [p=<0.0001 OR=2.41 (95% CI 1.54-3.80)]
      and incidence [p=0.001 OR=3.10 (95% CI 1.72-5.57)] of N. caninum. No association
      with region of Ireland was found for either testing positive for or incidence of
      N. caninum, or L. hardjo. There was however a tendency towards a higher incidence
      of Salmonella in regions of Ireland with higher cattle densities.

PMID- 23117042
TI  - From particle to platelet: optimization of a stable, high brightness fluorescent
      nanoparticle based cell detection platform.
AB  - Nanoparticles are increasingly used as diagnostic tools due to the ease with
      which their surface chemistry, optical and physical properties can be controlled.
      Molecules, drugs, enzymes and fluorophores can be protected within the particle
      core or conjugated externally conferring nanoparticle biocompatibility, target
      specificity or environmental sensitivity. This study details the development and
      characterisation of stable, bright, dye-doped silica nanoparticles which are
      surface functionalised with PAMAM dendrimers to enable efficient conjugation to
      platelet activation-specific antibodies. We present the physical and optical
      properties and demonstrate colloidal stability. We also provide the first
      evidence of how NPs can be employed to specifically label human platelets
      immobilised on a lab-on-a-chip platform. Using a single step protocol, we
      demonstrate highly specific platelet labelling with the distribution of antibody
      conjugated NPs matching that expected for the platelet GPIIb/IIIa receptor. The
      work highlights the potential of functionalized fluorescent NPs as diagnostic
      tools for cardiovascular disease. FROM THE CLINICAL EDITOR: This study details
      the development and characterization of PAMAM dendrimer functionalized, stable,
      and bright dye-doped silica nanoparticles that enable efficient conjugation to
      platelet activation-specific antibodies. These fluorescent NPs may specifically
      label human platelets that can be used as diagnostic tools for cardiovascular
      disease.

PMID- 23117044
TI  - Altered sensitivity to nitric oxide donors, induced by intravascular infusion of
      quantum dots, in murine mesenteric arteries.
AB  - Quantum dots (QDs) are utilised in imaging diagnostics, tissue engineering and
      medical therapeutics, however, their influence on vascular function is not
      ascertained. Here, we examined small mesenteric arterial responses after acute
      intravascular exposure to QDs. Incubation in mercaptoundecanoic acid (MUA)-coated
      QDs (at 15 MUg/mL) had no influence on endothelial-dependent dilator responses
      (Acetylcholine; Ach) but led to an attenuated relaxation to the nitric oxide
      donor, sodium nitroprusside (SNP). Conversely, incubation in POSS-PCU coated QDs
      (at 15 MUg/mL) led to attenuated Ach responses (10(-11)-10(-3)M; n=5, P<0.05),
      but had no influence on SNP-induced relaxation. At lower concentrations of POSS
      PCU coated QDs (5 MUg/mL), Ach responses were preserved. We demonstrate that
      acute exposure to QDs, can attenuate vasodilation but not vasoconstriction, and
      is dependent on their surface coatings. Our findings have implications in QD use
      for imaging diagnostics in disease states, where SNP based drugs are used in
      therapeutic intervention. FROM THE CLINICAL EDITOR: In this paper, the influence
      of quantum dots on vascular function is investigated---an important aspect to
      consider with the growing utility of quantum dots in imaging diagnostics, tissue
      engineering and medical therapeutics.

PMID- 23117043
TI  - Photoinduced electron-transfer mechanisms for radical-enhanced photodynamic
      therapy mediated by water-soluble decacationic C70 and C84O2 Fullerene
      Derivatives.
AB  - Fullerenes are promising candidates for photodynamic therapy (PDT). Thus, C70 and
      novel C84O2 fullerenes were functionalized with and without an additional deca
      tertiary ethyleneamino-chain as an electron source, giving rise to two distinct
      pairs of photosensitizers, the monoadducts LC-17, LC-19 and the bisadducts LC18
      and LC-20 to perform PDT in HeLa cells with UVA, blue, green, white and red
      light. Shorter wavelengths gave more phototoxicity with LC-20 while LC-19 was
      better at longer wavelengths; the ratio between killing obtained with LC-19 and
      LC-20 showed an almost perfect linear correlation (R = 0.975) with wavelength.
      The incorporation of a deca-tertiary amine chain in the C84O2 fullerene gave more
      PDT killing when excited with shorter wavelengths or in the presence of low
      ascorbate concentration through higher generation of hydroxyl radicals.
      Photoactivated C84O2 fullerenes induced apoptosis of HeLa cancer cells, together
      with mitochondrial and lysosomal damage demonstrated by acridine orange and
      rhodamine 123 fluorescent probes. FROM THE CLINICAL EDITOR: Photoactivated C70
      and C84O2 fullerenes were demonstrated to induce apoptosis of HeLa cancer cells,
      together with mitochondrial and lysosomal damage, as a function of wavelength.
      The study is paving the way to future clinical uses of these agents in
      photodynamic therapy.

PMID- 23117045
TI  - Poly (ethylene)-glycol conjugated solid lipid nanoparticles of noscapine improve
      biological half-life, brain delivery and efficacy in glioblastoma cells.
AB  - Noscapine crosses blood-brain-barrier and inhibits proliferation of glioblastoma
      cells. However, short plasma half-life and rapid elimination necessitate the
      administration of multiple injections for successive chemotherapy. Noscapine
      bearing solid lipid nanoparticles, Nos-SLN and poly (ethylene)-glycol conjugated
      solid lipid nanoparticles of noscapine, Nos-PEG-SLN of 61.3 +/- 9.3-nm and 80.5
      +/- 8.9-nm containing 80.4 +/- 3.2% and 83.6 +/- 1.2% of Nos, were constructed.
      First order kinetic and Higuchi equation were followed to release the Nos at
      intracellular pH~4.5. Further, a decrease in IC50 (Nos; 40.5 MUM>Nos-SLN; 27.2
      MUM>20.8 MUM) and enhanced subG1 population were observed in U87cells. Plasma
      half-life was enhanced up to ~11-fold and ~5-fold by Nos-PEG-SLN and Nos-SLN
      which significantly (P<0.05) deposits 400.7 MUg/g and 313.1 MUg/g of Nos in
      comparison to 233.2 MUg/g by drug solution. This is first report demonstrating a
      workable approach to regulate the administration of multiple injections of Nos,
      warranting further in vivo tumor regression study for superior management of
      brain cancer. FROM THE CLINICAL EDITOR: This report describes a possible approach
      to regulate the administration of multiple injections of Noscapine using solid
      lipid nanoparticles. The data warrant further in vivo tumor regression studies
      for optimal management of glioblastoma, a generally very poorly treatable brain
      cancer.

PMID- 23117047
TI  - Development and optimization of thiolated dendrimer as a viable mucoadhesive
      excipient for the controlled drug delivery: an acyclovir model formulation.
AB  - In the present study we report the development of novel thiolated dendrimers for
      mucoadhesive drug delivery. The thiolated dendrimers were synthesized by
      conjugating PAMAM dendrimer (G3.5)with cysteamine at two different molar ratios,
      i.e. 1:30 (DCys1) and 1:60 (DCys2). The thiolated dendrimers were further
      encapsulated with acyclovir (DCys1Ac and DCys2Ac) and the conjugates were
      characterized for thiol content, drug loading, drug release, and mucoadhesive
      behavior. The thiolated dendrimer conjugates showed thiol content of 10.56 +/-
      0.34 and 68.21 +/- 1.84 MUM/mg of the conjugate for DCys1 and DCys2,
      respectively. The acyclovir loading was observed to be highest in dendrimer drug
      conjugate (DAc) compared to other DCys1Ac and DCys2Ac conjugates. The thiolated
      dendrimers showed sustained release of acyclovir and showed higher mucoadhesion.
      The in vitro mucoadhesive activity of DCys2Ac was 1.53 and 2.89 fold higher
      mucoadhesion compared to DCys1Ac and DAc, respectively. These results
      demonstrated the usefulness of thiolated dendrimers as a mucoadhesive carrier and
      represent a novel platform for drug delivery. FROM THE CLINICAL EDITOR: This
      study demonstrates the utility of thiolated dendrimers as mucoadhesive carriers
      as reported in an acyclovir delivery model system.

PMID- 23117046
TI  - Comparative cellular pharmacokinetics and pharmacodynamics of siRNA delivery by
      SPANosomes and by cationic liposomes.
AB  - Mechanistic understanding of intracellular trafficking is important for the
      development of small interfering RNA (siRNA) delivery vehicles. Here, we describe
      a novel methodology to quantitatively analyze nanocarrier-mediated disposition of
      siRNA. Cellular uptake and cytoplasmic release of siRNA over time were quantified
      by measuring the fluorescence intensities of fluorescently-labeled siRNAs and
      molecular beacons using flow cytometry. This method was used to investigate the
      cellular pharmacokinetics (PK) of siRNA delivery by SPANosomes (SP) and by
      cationic liposomes (CL). The results showed that the superior pharmacodynamic
      (PD) response of SP was because it enhanced transport of siRNA into the cytoplasm
      compared to the CL. The divergent cellular pharmacokinetic profiles of the two
      formulations were associated with different cellular entry pathways. These
      findings can facilitate the rational design of more efficient siRNA delivery
      vehicles in the future. FROM THE CLINICAL EDITOR: In this paper the authors
      describe a novel methodology to quantitatively analyze nanocarrier-mediated
      disposition of small interfering RNA, comparing SPANosomes with cationic
      liposomes as delivery systems with different entry pathways.

PMID- 23117048
TI  - Characterization of carbon nanotube protein corona by using quantitative
      proteomics.
AB  - The protein corona of a nanomaterial is a complex layer of proteins spontaneously
      and stably formed when the material is exposed to body fluids or intracellular
      environments. In this study, we utilised stable isotope labeling by amino acids
      in cell culture (SILAC)-based quantitative proteomics to characterise the binding
      of human cellular proteins to two forms of carbon nanoparticles: namely multi
      walled carbon nanotubes (MWCNTs) and carbon black (CB). The relative binding
      efficiency of over 750 proteins to these materials is measured. The data indicate
      that MWCNTs and CB bind to vastly different sets of proteins. The molecular basis
      of selectivity in protein binding is investigated. This study is the first large
      scale characterisation of protein corona on CNT, providing the biochemical basis
      for the assessment of the suitability of CNTs as biomedical tools, and as an
      emerging pollutant. FROM THE CLINICAL EDITOR: This team of investigators
      performed the first large-scale characterization of protein corona on carbon
      nanotubes, studying 750 proteins and assessing the suitability of CNTs as
      biomedical tools and as an emerging pollutant.

PMID- 23117050
TI  - Effects of psychological nursing intervention on personality characteristics and
      quality of life of patients with esophageal cancer.
AB  - OBJECTIVE: This study examined the effects of a psychological nursing
      intervention on personality characteristics and quality of life of esophageal
      cancer patients. METHODOLOGY: Esophageal cancer patients (n=86) were randomized
      into either an intervention group (n=45) or a control group (n=41). Patients in
      the control group were given routine nursing care, and those in the intervention
      group were provided with psychological nursing interventions in addition to
      routine nursing care. Personality characteristics, assessed through Eysenck
      Personality Questionnaire, and quality of life, assessed through EORTC QLQ-C30,
      were compared between the two groups. RESULTS: The results showed that
      personality characteristics were closely related to quality of life. After the
      psychological nursing intervention, the main factors were neurosis, psychosis or
      mood instability, and personality stability. However, introverted and extroverted
      personality characteristics were not associated with quality of life. The
      psychological nursing intervention was associated with decreased P-scale and E
      scale scores of personality characteristics and improved quality of life in each
      dimension scored. CONCLUSIONS: A psychological nursing intervention can affect
      the personality characteristics of esophageal cancer patients and improve their
      quality of life; this approach is worthy of further study and clinical
      application.

PMID- 23117051
TI  - The human operational sex ratio: effects of marriage, concealed ovulation, and
      menopause on mate competition.
AB  - Among mammals, male-male competition for sexual access to females frequently
      involves fighting. Larger body size gives males an advantage in fighting, which
      explains why males tend to be larger than females in many species, including
      anthropoid primates. Mitani et al. derived a formula to measure the operational
      sex ratio (OSR) to reflect the degree of male-male competition using the number
      of reproductively available males to females who are cycling and capable of
      conceiving. The OSR should predict the degree of sexual dimorphism in body mass
      at least if male-male competition involves much fighting or threatening. Here, we
      use hunter-gatherer demographic data and the Mitani et al. formula to calculate
      the human OSR. We show that humans have a much lower degree of body mass sexual
      dimorphism than is predicted by our OSR. We suggest this is because human
      competition rarely involves fighting. In human hunter-gatherer societies,
      differences in the ages of marriage have an impact on competition in that the age
      of males at first marriage is younger when there is a lower percentage of married
      men with two or more wives, and older when there is a higher percentage of
      married men with two or more wives. We discuss the implications of this for
      females, along with the effects of two key life history traits that influence the
      OSR, concealed ovulation and menopause. While menopause decreases the number of
      reproductively available females to males and thus increases male-male
      competition, concealed ovulation decreases male-male competition. Finally, we
      discuss the importance of mostly monogamous mate bonds in human evolution.

PMID- 23117049
TI  - The role of base excision repair genes OGG1, APN1 and APN2 in benzo[a]pyrene-7,8
      dione induced p53 mutagenesis.
AB  - Lung cancer is primarily caused by exposure to tobacco smoke. Tobacco smoke
      contains numerous carcinogens, including polycyclic aromatic hydrocarbons (PAH).
      The most common PAH studied is benzo[a]pyrene (B[a]P). B[a]P is metabolically
      activated through multiple routes, one of which is catalyzed by aldo-keto
      reductase (AKR) to B[a]P-7,8-dione (BPQ). BPQ undergoes a futile redox cycle in
      the presence of NADPH to generate reactive oxygen species (ROS). ROS, in turn,
      damages DNA. Studies with a yeast p53 mutagenesis system found that the
      generation of ROS by PAH o-quinones may contribute to lung carcinogenesis because
      of similarities between the patterns (types of mutations) and spectra (location
      of mutations) and those seen in lung cancer. The patterns were dominated by G to
      T transversions, and the spectra in the experimental system have mutations at
      lung cancer hotspots. To address repair mechanisms that are responsible for BPQ
      induced damage we observed the effect of mutating two DNA repair genes OGG1 and
      APE1 (APN1 in yeast) and tested them in a yeast reporter system for p53
      mutagenesis. There was an increase in both the mutant frequency and the number of
      G:C/T:A transversions in p53 treated with BPQ in ogg1 yeast but not in apn1
      yeast. Knocking out APN2 increased mutagenesis in the apn1 cells. In addition, we
      did not find a strand bias on p53 treated with BPQ in ogg1 yeast. These studies
      suggest that Ogg1 is involved in repairing the oxidative damage caused by BPQ,
      Apn1 and Apn2 have redundant functions and that the stand bias seen in lung
      cancer may not be due to impaired repair of oxidative lesions.

PMID- 23117052
TI  - Infradiagnosed complications of chronic diabetes mellitus: the value of
      systematic review in a single visit.
AB  - INTRODUCTION: Early diagnosis of diabetes mellitus complications reduces their
      progression and therefore improves quality of life and decreases cardiovascular
      mortality. OBJECTIVES: To evaluate the efficiency of a unit for detection of
      chronic complications of diabetes, and to analyze the incidence and prevalence of
      complications in a sample of patients from our area of interest and concern.
      METHODS: A cross-sectional study performing routine screening of all diabetes
      complications in patients aged 18-80 years diagnosed with type 1 or type 2
      diabetes mellitus at least 6 months before. Anthropometric variables were
      measured and data on drug treatment and the most recent lipid profile were
      collected. RESULTS: 460 patients were included in the study. The prevalence and
      incidence rates of chronic complications of diabetes were 57% and 35.4%
      respectively. Glycosylated hemoglobin values <= 7% were found in 42% of patients,
      blood pressure levels below 130/80 mmHg in 20% of patients, and LDL cholesterol
      levels less than 2.59 mmol/L in 46% of patients. Patients with new complications
      were older and had higher BMI and hip circumference values, as well as higher
      systolic blood pressure levels and greater use of antihypertensive drugs.
      CONCLUSION: A unit for routine screening of chronic complications of diabetes
      would allow for detection of macroangiopathy and microangiopathy in a single
      annual visit, increasing visit compliance, and for implementation of measures to
      prevent its progression.

PMID- 23117053
TI  - [Epicardial adipose tissue: more than a simple fat deposit?].
AB  - Obesity increases the risk of development of atherosclerosis. However, this risk
      significantly depends on adipose tissue distribution in the body and ectopic
      accumulation of visceral adipose tissue (VAT). Recent evidence suggests that each
      visceral fat deposit is anatomically and functionally different. Due to proximity
      to the organ, each visceral fat deposit exerts a local modulation rather than a
      systemic effect. Because of its unique location and biomolecular properties, a
      "non-traditional" fat depot - the epicardial adipose tissue - has been considered
      to play a causative role in atherosclerosis. Epicardial adipose tissue may be
      measured with imaging techniques and is clinically related to left ventricular
      mass, coronary artery disease, and metabolic syndrome. Therefore, epicardial fat
      measurement may play a role in stratification of cardiometabolic risk and may
      serve as a therapeutic target. 

PMID- 23117054
TI  - The boundaries of epilepsy: where is the limit? A reply to Labate and
      Gambardella.

PMID- 23117055
TI  - Anosognosia, autobiographical memory and self knowledge in Alzheimer's disease.
AB  - This article explores the relationship between lack of awareness of
      neuropsychological deficit, also termed anosognosia, and loss of self knowledge
      in Alzheimer's disease (AD). Specifically, it considers the hypothesis that
      anosognosia in AD can in part be explained by a loss of mnemonic ability in which
      knowledge about self-ability is degraded. To ground this hypothesis, we review
      evidence suggesting failure to update personal knowledge concerning task
      efficacy, loss of recollection with relative amplification of semanticization
      processes and loss of an updated representation of the self. We present a
      theoretical formulation as to how the features of memory impairment in AD may
      contribute to anosognosia, incorporating these notions in a reformulation of the
      Cognitive Awareness Model.

PMID- 23117056
TI  - A closer look at GE corn findings.

PMID- 23117057
TI  - Effects of masker envelope irregularities on tone detection in narrowband and
      broadband noise maskers.
AB  - Introducing coherent masker envelope modulation to frequency regions neighboring
      the signal frequency can reduce detection thresholds for a pure-tone signal.
      Verhey and Ernst (2009) reported that irregular masker modulation conferred
      greater benefit than regular modulation when the masker was broadband, but that
      there was no difference when the masker was narrowband. The present study
      evaluated two possible explanations for this result: one based on modulation
      adaptation and the other based on the introduction of relatively long-duration
      modulation minima in the irregular masker modulation condition. The first
      experiment replicated the results of Verhey and Ernst (2009), but also included
      conditions in which a 12.5-ms signal was presented in a 12.5-ms modulation
      minimum, which was exempted from envelope jitter. The second experiment used a
      continuous masker and suspended jitter during epochs associated with either a
      12.5- or 87.5-ms signal. No benefit of masker envelope irregularity before or
      after the signal was observed in either experiment. These findings are
      inconsistent with an explanation based on modulation adaptation, implicating
      instead the introduction of relatively long-duration modulation minima in the
      large masking release obtained for a long-duration signal in an irregularly
      modulated masker.

PMID- 23117058
TI  - One-on-one education and client reminders increase uptake of colorectal, breast
      and cervical cancer screening.
AB  - Implications for practice and research: Client reminders and one-on-one education
      are effective community-based interventions for improving screening rates for
      colorectal cancer (CRC), breast and cervical cancers. Group education is now
      shown to be an effective approach for improving breast cancer screening rates.
      Needs particular to the target population should be considered in conjunction
      with published recommendations when choosing interventions to improve screening
      rates. Studies which address interventions for increasing CRC screening other
      than with faecal occult blood test are needed. An important area to address in
      future research is the effectiveness of electronic communications in improving
      screening rates.

PMID- 23117059
TI  - Risk of cervical cancer after completed post-treatment follow-up of cervical
      intraepithelial neoplasia: population based cohort study.
AB  - OBJECTIVE: To compare the risk of cervical cancer in women with histologically
      confirmed cervical intraepithelial neoplasia who returned to routine screening
      after having completed post-treatment follow-up with consecutive normal smear
      test results with women with a normal primary smear test result. DESIGN:
      Population based cohort study using data from a nationwide pathology register.
      SETTING: The Netherlands, 1994 to 2006. POPULATION: 38,956 women with
      histologically confirmed intraepithelial neoplasia grades 1 to 3 with completed
      follow-up after treatment. INTERVENTION: Routine post-treatment follow-up of
      cervical intraepithelial neoplasia, recommending smear tests at six, 12, and 24
      months. MAIN OUTCOME MEASURE: Incidence of cervical cancer in the period from
      completed follow-up with negative test results after cervical intraepithelial
      neoplasia to the next primary test. 10-year hazard ratios were compared with
      periods after normal results for the primary smear test, adjusted for year in
      follow-up. RESULTS: 20 cervical cancers were diagnosed during 56,956 woman years
      after completed follow-up of cervical intraepithelial neoplasia, whereas 1613
      cervical cancers were diagnosed during 25,020,697 woman years after a normal
      primary smear test result. The incidence of 35.1 (95% confidence interval 21.4 to
      54.2) per 100,000 woman years and 6.4 (6.1 to 6.8) per 100,000 woman years,
      respectively, led to an adjusted hazard ratio of 4.2 (95% confidence interval 2.7
      to 6.5) for periods after completed follow-up compared with periods after normal
      primary smear test results. This hazard ratio was increased for all ages. No
      significant difference in risk of cervical cancer was observed by grade of
      cervical intraepithelial neoplasia. CONCLUSIONS: An excess risk of cervical
      cancer previously observed for women treated for cervical intraepithelial
      neoplasia was also observed in the subgroup of women who completed their post
      treatment follow-up with three consecutive normal smear test results. The overall
      corrected risk of cervical cancer in these women was increased fourfold 35 cases
      per 100,000 woman years) compared with women with normal primary smear test
      results (6 per 100,000 woman years).

PMID- 23117061
TI  - Follow-up after treatment for cervical intraepithelial neoplasia.

PMID- 23117060
TI  - Cost effectiveness of human papillomavirus test of cure after treatment for
      cervical intraepithelial neoplasia in England: economic analysis from NHS
      Sentinel Sites Study.
AB  - OBJECTIVES: To evaluate the cost effectiveness of human papillomavirus testing
      after treatment for cervical intraepithelial neoplasia (CIN). DESIGN: Economic
      analysis using a Markov modelling approach to combine cost and epidemiological
      data from the NHS Sentinel Sites Study with data from previous studies of post
      treatment recurrence rates. SETTING: English NHS Cervical Cancer Screening
      Programme. INTERVENTIONS: Management guidelines after treatment of CIN involving
      annual cytology follow-up for 10 years, compared with alternative protocols using
      the human papillomavirus test to reduce the amount of post-treatment
      surveillance. MAIN OUTCOME MEASURES: Cases of underlying CIN3+ averted at 10
      years and costs per 1000 women treated. RESULTS: Model predictions indicated
      that, at observed levels of compliance with post-treatment recommendations,
      management with only cytological follow-up would result in 29 residual cases of
      recurrent CIN3+ by 10 years and would cost L358,222 (?440,426; $574,910)
      (discounted) per 1000 women treated. Implementation of human papillomavirus test
      of cure in cytologically negative women according to the sentinel sites protocol
      would avert an additional 8.4 cases of CIN 3+ and reduce costs by L9388 per 1000
      women treated. CONCLUSIONS: Human papillomavirus test of cure would be more
      effective and would be cost saving compared with cytology only follow-up. The
      results of this evaluation support the full scale implementation of human
      papillomavirus test of cure after treatment of CIN within the NHS Cervical
      Screening Programme.

PMID- 23117062
TI  - Otx2 selectively controls the neurogenesis of specific neuronal subtypes of the
      ventral tegmental area and compensates En1-dependent neuronal loss and MPTP
      vulnerability.
AB  - Understanding the molecular basis underlying the neurogenesis of mesencephalic
      diencephalic Dopaminergic (mdDA) neurons is a major task fueled by their
      relevance in controlling locomotor activity and emotion and their involvement in
      neurodegenerative and psychiatric diseases. Increasing evidence suggests that
      mdDA neurons of the substantia nigra pars compacta (SNpc) and ventral tegmental
      area (VTA) represent two main distinct neuronal populations, which, in turn,
      include specific neuronal subsets. Relevant studies provided important results on
      mdDA neurogenesis, but, nevertheless, have not yet clarified how the identity of
      mdDA neuronal subtypes is established and, in particular, whether neurogenic
      factors may direct progenitors towards the differentiation of specific mdDA
      neuronal subclasses. The transcription factor Otx2 is required for the
      neurogenesis of mesencephalic DA (mesDA) neurons and to control neuron subtype
      identity and sensitivity to the MPTP neurotoxin in the adult VTA. Here we studied
      whether Otx2 is required in mdDA progenitors for the generation of specific mdDA
      neuronal subtypes. We found that although expressed in virtually all mdDA
      progenitors, Otx2 is required selectively for the differentiation of VTA neuronal
      subtypes expressing Ahd2 and/or Calb but not for those co-expressing Girk2 and
      glyco-Dat. Moreover, mild over-expression of Otx2 in SNpc progenitors and neurons
      is sufficient to rescue En1 haploinsufficiency-dependent defects, such as
      progressive loss and increased MPTP sensitivity of SNpc neurons. Collectively,
      these data suggest that mdDA progenitors exhibit differential sensitivity to
      Otx2, which selectively influences the generation of a large and specific subset
      of VTA neurons. In addition, these data suggest that Otx2 and En1 may share
      similar properties and control survival and vulnerability to MPTP neurotoxin
      respectively in VTA and SNpc.

PMID- 23117063
TI  - Clatter on the electrocardiogram.
AB  - An ECG recorded from a patient with an implanted cardiac pacemaker showed a
      striking high frequency pulsing on the ST-T segments linked with each QRS
      complex. In this report we present an approach to the clatter on the ECG and
      discuss various potential diagnoses that can have closely similar pattern.

PMID- 23117064
TI  - Radiation dose-rate and DNA damage.

PMID- 23117065
TI  - Mycoplasma removal: simple curative methods for viral supernatants.
AB  - As a partner of the European Virus Archive (EVA) FP7 infrastructure, our research
      group is maintaining and developing a large virus collection. To meet the
      standards of the quality management system adopted by all European Virus Archive
      partners, the detection and eradication of mycoplasma in cell culture
      supernatants (stored at -80 degrees C or freeze-dried) has to be improved.
      Although the methods for mycoplasma elimination from infected cell lines were
      largely described, the decontamination procedures of precious cell culture
      supernatants was poorly documented. In this study, a large panel of mycoplasma
      contaminated virus stocks (enveloped and non enveloped, RNA and DNA viruses) was
      tested successfully for mycoplasma removal using two simple optimized methods.
      These easy-to-perform protocols, using respectively PlasmocinTM (InvivoGen,
      Cayla, France) and chloroform, were shown to remove mycoplasma completely from
      cell supernatant without incidence in viral infectivity.

PMID- 23117066
TI  - Dihydroxy-isosteviol-methyl-ester, an active biological component of Pulsatilla
      nigricans, reduces arsenic induced cellular dysfunction in testis of male mice.
AB  - Arsenic contamination has become a menacing health concern, warranting search for
      new drugs capable of ameliorating its toxicity. Extract of Pulsatilla nigricans
      is occasionally used as traditional medicine including homeopathy to
      combat/alleviate toxicity-related symptoms of known or unknown cause. Mice were
      intoxicated with a sub-lethal dose of sodium arsenite (20mg/kg b.w./day,
      determined through a range-finding trial) and the effect on testicular toxicity
      after 30, 60, and 90 days was examined. We observed an increased level of
      reactive oxygen species, cellular damage in testes of SA-intoxicated mice and
      further analysed expressions of apoptotic signal proteins and mRNA like Bax, Bcl2
      and caspase3. Treatment with EEPN showed significant inhibition/reversal of the
      arsenic-induced toxic effect in testis and reduced oxidative stress through
      modulating expressions of signal proteins, thereby inhibiting the progression of
      events of apoptosis in testis cells and sperm. Therefore, EEPN has potentials for
      therapeutic use in arsenic- induced reproductive toxicity.

PMID- 23117067
TI  - Interaction of triphenyltin and an agonist of retinoid X receptor (LGD1069) in
      embryos of Xenopus tropicalis.
AB  - Xenopus tropicalis embryos were exposed for 48 h to mixtures of triphenyltin and
      LGD1069 (an agonist of the retinoid X receptor). The index of fin deficiency
      (IFD) of the embryos increased in the triphenyltin-treated groups, and the index
      of axis deficiency (IAD) increased in LGD1069-treated groups in a concentration
      dependent manner. When embryos were exposed to mixtures of 5MUgSn/L triphenyltin
      and 1-30 MUg/L LGD1069, IFD decreased from 2.9 to 0.6 and IAD increased from 0.1
      to 2.4 with increasing LGD1069 concentrations. Conversely, when embryos were
      exposed to mixtures of 15 MUg/L LGD1069 and 1-10 MUg Sn/L triphenyltin, IFD
      increased from 0.1 to 3.0 with increasing triphenyltin concentrations. Co
      exposure induced some new phenotypes, such as posteriorized anus. These results
      suggest that LGD1069 suppressed the teratogenicity of triphenyltin and that the
      retinoid X receptor was involved in triphenyltin-induced teratogenicity.
      Histological observations indicate that co-exposure inhibited the invagination of
      the yolk plug.

PMID- 23117068
TI  - Effects of isoflurane inhalation on the male reproductive system in rats.
AB  - The 15-day intact adult male assay was used to evaluate effects of isoflurane on
      the testes and sexual hormones. Forty adult male Sprague-Dawley rats were divided
      into five groups exposed to air containing 0, 50, 300, 1800 or 10,800 ppm
      isoflurane. After the treatments, serum was collected for the hormones assay. The
      right testis was to be used for daily sperm production. The left testis was
      processed for histopathology and electron microscopy observation. Daily sperm
      productions were significantly decreased at doses of 300, 1800 and 10,800 ppm.
      Impaired seminiferous tubules were noted at doses of 300, 1800 and 10,800 ppm.
      Ultrastructural changes included nucleus agglutination of spermatocytes, big
      lipid drops and autophagosome in cytoplasm. The serum follicle-stimulating
      hormone and testosterone concentrations reduced significantly at doses of 1800
      and 10,800 ppm. Isoflurane induced impairments of seminiferous tubules and
      spermatogenesis. The testicular damages caused by isoflurane can be related to
      the imbalances in the sexual hormones.

PMID- 23117070
TI  - New insights into the chemical and isotopic composition of human-body
      biominerals. I: Cholesterol gallstones from England and Greece.
AB  - We have analyzed gallstones from four patients of Europe and particularly from
      England (including samples from a mother and a daughter) and Greece. According to
      the XRD, FTIR, NMR and laser micro-Raman results the studied materials correspond
      to typical cholesterol monohydrate (ChM). The micro-morphology of cholesterol
      microcrystals was investigated by means of SEM-EDS. The XRF results revealed that
      Ca is the dominant non-organic metal in all gallstones (up to ~1.95wt.%) together
      with Fe, Cu, Pb and Ni (up to ~19ppm for each metal). Gallstones from England
      contain additional Mn (up to ~87ppm) and Zn (up to ~6ppm) while the sample of the
      mother contains negligible Zn and Mn, compared to that of her daughter, but
      significant As (~4.5ppm). All cholesterol gallstones examined are well enriched
      in potentially toxic metals (Pb, as well as Ni in one case) and metalloids (As
      also in one case) as compared to the global average. The position of Zn, which is
      a characteristic biometal, in the structure of cholesterol, was investigated by
      molecular simulation using the Accelrys Materials Studio((r)) software. On the
      basis of IRMS results, all gallstones examined exhibit a very light delta(13)C
      signature (average delta(13)C ~-240/00 PDB). Gamma-ray spectrometry measurements
      indicate the presence of (214)Pb and (214)Bi natural radionuclides due to the
      (238)U series as well as an additional amount of (40)K.

PMID- 23117069
TI  - Methyl methanesulfonate induces apoptosis in p53-deficient H1299 and Hep3B cells
      through a caspase 2- and mitochondria-associated pathway.
AB  - Methyl methanesulfonate (MMS) has been shown to induce apoptosis in various cell
      types through p53-dependent pathways. Nevertheless, pharmacological and genetic
      blockade of p53 functions results in similar or delayed sensitivity to MMS
      treatment, suggesting the presence of p53-independent apoptotic mechanisms. To
      understand the p53-independent mechanisms that are engaged during MMS-induced
      apoptosis, we established MMS-induced apoptotic cell models using p53-deficient
      H1299 and Hep3B cells. Our results demonstrated that MMS at concentrations of 50,
      100, 200, 400 and 800 MUM induced the formation of gammaH2AX foci, and that at
      higher concentrations, 400 and 800 MUM, MMS treatment led to apoptosis in the two
      cell lines. This apoptotic cell death was concurrent with the loss of
      mitochondrial membrane potential, nuclear-cytosolic translocation of active
      caspase 2, release of cytochrome c from mitochondria, and the cleavage of caspase
      9, caspase 3 and PARP. However, MMS-induced DNA damage failed to stabilize the
      p53 family members TAp73 and DNp73. These results demonstrated a p53- and p73
      independent mechanism for MMS-induced apoptosis that involves the nuclear
      cytosolic translocation of active caspase 2 as well as the mitochondria-mediated
      pathway.

PMID- 23117071
TI  - Growth modulation index as metric of clinical benefit assessment among advanced
      soft tissue sarcoma patients receiving trabectedin as a salvage therapy.
AB  - BACKGROUND: The growth modulation index (GMI) is the ratio of time to progression
      with the nth line (TTP(n)) of therapy to the TTP(n)(-1) with the n-1th line. GMI
      >1.33 is considered as a sign of activity in phase II trials. PATIENTS AND
      METHODS: This retrospective analysis evaluated the concordance between the GMI
      and the efficacy outcomes in 279 patients with advanced soft tissue sarcoma
      (ASTS) treated with trabectedin 1.5 mg/m2 (24-h infusion every 3 weeks) in four
      phase II trials. RESULTS: One hundred and forty-two (51%) patients received one
      prior line and 137 >= 2 lines. The median TTP(n) was 2.8 months (range 0.2-26.8),
      whereas the median TTP(n)(-1) was 4.0 months (0.3-79.5). The median GMI was 0.6
      (0.0-14.4). Overall, 177 patients (63%) had a GMI <1; 21 (8%) a GMI equal to 1
      1.33 and 81 (29%) a GMI >1.33, which correlated with the median overall survival
      in those patients (9.1, 13.9 and 23.8 months, respectively, P = 0.0005). A high
      concordance rate between the GMI and response rate (P < 0.0001) and progression
      free survival (PFS, P < 0.0001) was observed. Good performance status (PS) was
      the only factor associated with GMI >1.33 (PS = 0; P < 0.04). CONCLUSIONS: A high
      GMI was associated with favorable efficacy outcomes in patients treated with
      trabectedin. Further research is needed to assess GMI as an indicator in this
      setting.

PMID- 23117072
TI  - Influence of enzyme and transporter polymorphisms on trough imatinib
      concentration and clinical response in chronic myeloid leukemia patients.
AB  - BACKGROUND: This study explored the impact of genetic polymorphisms in cytochrome
      P450 (CYP) enzymes and transporters on the plasma trough concentration of
      imatinib mesylate (IM) and clinical response in chronic myeloid leukemia (CML).
      PATIENTS AND METHODS: In total, 82 patients with CML who had been administered
      400 mg IM daily for over 6 months were genotyped for 11 single-nucleotide
      polymorphisms in nine genes (CYP3A4, CYP3A5, CYP2C9, CYP2C19, CYP2D6, ABCB1,
      SLC22A1, SLC22A2 and ABCG2) using blood samples. The trough imatinib
      concentration and clinical responses were assessed 6 months after the initiation
      of IM therapy. RESULTS: The CC, CA and AA genotypes in ABCG2 421C>A gave
      significantly different frequencies for the major molecular response (MMR) (P =
      0.02). However, no significant differences were found between the genotypes of
      the CYP enzymes and transporters identified in this study and the imatinib plasma
      trough concentrations and clinical response frequencies, except for the
      correlation of ABCG2 with MMR. CONCLUSIONS: The results of the present study may
      indicate that the ABCG 421C>A genetic polymorphism influences the MMR of imatinib
      in patients with CML.

PMID- 23117073
TI  - Efficacy and safety of single-dose fosaprepitant in the prevention of
      chemotherapy-induced nausea and vomiting in patients receiving high-dose
      cisplatin: a multicentre, randomised, double-blind, placebo-controlled phase 3
      trial.
AB  - BACKGROUND: We evaluated the efficacy and safety of single-dose fosaprepitant in
      combination with intravenous granisetron and dexamethasone. PATIENTS AND METHODS:
      Patients receiving chemotherapy including cisplatin (>=70 mg/m(2)) were eligible.
      A total of 347 patients (21% had received cisplatin with vomiting) were enrolled
      in this trial to receive the fosaprepitant regimen (fosaprepitant 150 mg,
      intravenous, on day 1 in combination with granisetron, 40 MUg/kg, intravenous, on
      day 1 and dexamethasone, intravenous, on days 1-3) or the control regimen
      (placebo plus intravenous granisetron and dexamethasone). The primary end point
      was the percentage of patients who had a complete response (no emesis and no
      rescue therapy) over the entire treatment course (0-120 h). RESULTS: The
      percentage of patients with a complete response was significantly higher in the
      fosaprepitant group than in the control group (64% versus 47%, P = 0.0015). The
      fosaprepitant regimen was more effective than the control regimen in both the
      acute (0-24 h postchemotherapy) phase (94% versus 81%, P = 0.0006) and the
      delayed (24-120 h postchemotherapy) phase (65% versus 49%, P = 0.0025).
      CONCLUSIONS: Single-dose fosaprepitant used in combination with granisetron and
      dexamethasone was well-tolerated and effective in preventing chemotherapy-induced
      nausea and vomiting in patients receiving highly emetogenic cancer chemotherapy,
      including high-dose cisplatin.

PMID- 23117074
TI  - Comparison of the prognostic value of genomic grade index, Ki67 expression and
      mitotic activity index in early node-positive breast cancer patients.
AB  - Background The genomic grade index (GGI) completes the prognostic value of
      histological grade (HG). Other proliferation markers include the mitotic activity
      index (MAI) and the Ki67 immunohistochemistry (IHC) status. We compared the
      prognostic value of GGI, HG, MAI, Ki67 IHC and messenger RNA (mRNA) status in
      node-positive breast cancer (BC) patients treated with adjuvant anthracycline
      based chemotherapy in the prospective PACS01 trial.  Patients and methods The
      five proliferation-related parameters (GGI, Ki67 mRNA expression and centrally
      determined HG, MAI, and Ki67 IHC status) of tumours were available for 204 cases
      and analysed as continuous values. We compared the correlations of each one with
      the other proliferation-related parameters and with histoclinical variables
      including the disease-free survival (DFS).  Results Expected correlations were
      observed between the five parameters and for each parameter with biological
      features (hormone-receptor and HER2 status, molecular subtypes), but the GGI
      displayed the strongest correlations. The GGI outperformed the prognostic
      performance of the four other proliferation-related parameters for the DFS in all
      204 patients and in the 95 HG2 patients. In multivariate analysis including the
      classical prognostic factors, only GGI remained significant. Finally, the GGI
      outperformed the prognostic performance of MKI67 mRNA expression in a series of
      1599 samples and 656 HG2 cases.  Conclusions In this small pilot biomarker study
      ancillary to the PACS01 trial, the GGI outperforms the prognostic performance of
      centrally determined HG, MAI, Ki67 IHC status and mRNA expression. Further
      validation is warranted in larger series.

PMID- 23117075
TI  - Renal cell carcinoma and a constitutional t(11;22)(q23;q11.2): case report and
      review of the potential link between the constitutional t(11;22) and cancer.
AB  - We observed a t(11;22)(q23-24;q11.2-12) and monosomy 3 in renal tumor cells from
      a 72-year-old man. The hypothesis of a primitive peripheral neuroectodermal tumor
      (PPNET) located in the kidney was promptly excluded: Histologically, the tumor
      was a clear cell renal cell carcinoma (RCC) and we did not observe an EWSR1 gene
      rearrangement. The constitutional origin of this alteration was established. We
      report on the second case of RCC in a patient with a constitutional t(11;22). The
      t(11;22)(q23;q11.2) is the main recurrent germline translocation in humans.
      Unbalanced translocation can be transmitted to the progeny and can cause Emanuel
      syndrome. Our observation alerts cancer cytogeneticists to the fortuitous
      discovery of the constitutional t(11;22) in tumor cells. This translocation
      appears grossly similar to the t(11;22)(q24;q12) of PPNET and should be evoked if
      present in all cells of a tumor other than PPNET. This is important when
      providing appropriate genetic counseling. Moreover, the potential oncogenic role
      of the t(11;22) and its predisposing risk of cancer are under debate. The family
      history of the patient revealed a disabled brother who died at an early age from
      colon cancer and a sister with breast cancer. This observation reopens the issue
      of a link between the constitutional t(11;22) and cancer, and the utility of
      cancer prevention workups for t(11;22) carriers.

PMID- 23117076
TI  - The Melbourne Infant Feeding, Activity and Nutrition Trial (InFANT) Program
      follow-up.
AB  - BACKGROUND: The Melbourne Infant Feeding, Activity and Nutrition Trial (InFANT)
      Program, is a community-based, cluster-randomised controlled trial of an obesity
      prevention intervention delivered to first-time parents of infants from age 4-20
      months. Conducted from 2008 to 2010, the program had high uptake and retention
      and showed positive impacts on some dietary outcomes and television viewing.
      Funding was secured for a follow-up study of participants two and 3.5 years post
      intervention (at child ages ~3.5 and 5 years). The follow-up study aims to assess
      intervention effects, mediators and moderators of effects, and program cost
      effectiveness over the longer term. METHODS/DESIGN: The 492 families still
      enrolled in the Melbourne InFANT Program at intervention conclusion will be
      recontacted and renewed consent sought to participate in this follow-up study. No
      further intervention will occur. Home visit data collections will occur
      approximately two and 3.5 years post intervention. Main outcomes to be assessed
      include child body mass index, waist circumference, diet (3 * 24-hour recalls;
      food frequency questionnaire), physical activity (8 days ActiGraph accelerometer
      data; parent reported active play) and sedentary time (8days ActiGraph
      accelerometer and ActivPAL inclinometer data; parent reported screen time).
      DISCUSSION: Follow-up of participants of the Melbourne InFANT Program at two and
      3.5 years post intervention will allow assessment of longer term intervention
      effects, investigation of potential mediators and moderators of such effects, and
      economic evaluation of the longer term outcomes. This information will be
      valuable to researchers and policy makers in progressing the field of early
      childhood obesity prevention.

PMID- 23117077
TI  - The need for expanded monitoring of adverse events in behavioral health clinical
      trials.
AB  - Monitoring for possible adverse events is ethically required by Institutional
      Review Boards and Good Clinical Practice guidelines for all human research
      involving the delivery of treatment interventions in a clinical trial. The
      monitoring of adverse events is a well-established and routine practice for
      contemporary clinical trials involving medications and medical devices. However,
      these same guidelines have not been fully integrated into clinical trials
      involving the use of behavioral health interventions and psychotherapy. Most
      behavioral health clinical trials limit adverse event monitoring to serious
      adverse events such as suicide attempts, completed suicides, and psychiatric
      hospitalizations. Other possible "side effects" of psychotherapy, such as
      temporary increases in anxiety, are often considered a normal part of therapy and
      are therefore not documented as possible adverse events. This manuscript reviews
      a variety of reasons for the limited adverse event monitoring in behavioral
      health clinical trials and highlights the importance of incorporating expanded
      adverse event monitoring into future behavioral health clinical trials. Without
      understanding the nature and prevalence of adverse events, patients cannot be
      informed adequately of the possible risks and benefits of behavioral
      interventions prior to engaging in treatment.

PMID- 23117078
TI  - Breakthroughs in genomics data integration for predicting clinical outcome.

PMID- 23117081
TI  - Newly discovered atmospheric oxidant contributes to climate change, sulfuric acid
      production.

PMID- 23117083
TI  - [Hyperkalemia linked to intense physical activity: a rare complication in
      anorexia nervosa].

PMID- 23117082
TI  - Measurement of tissue acyl-CoAs using flow-injection tandem mass spectrometry:
      acyl-CoA profiles in short-chain fatty acid oxidation defects.
AB  - The primary accumulating metabolites in fatty acid oxidation defects are
      intramitochondrial acyl-CoAs. Typically, secondary metabolites such as
      acylcarnitines, acylglycines and dicarboxylic acids are measured to study these
      disorders. Methods have not been adapted for tissue acyl-CoA measurement in
      defects with primarily acyl-CoA accumulation. Our objective was to develop a
      method to measure fatty acyl-CoA species that are present in tissues of mice with
      fatty acid oxidation defects using flow-injection tandem mass spectrometry.
      Following the addition of internal standards of [(13)C(2)] acetyl-CoA, [(13)C(8)]
      octanoyl-CoA, and [C(17)] heptadecanoic CoA, acyl-CoA's are extracted from tissue
      samples and are injected directly into the mass spectrometer. Data is acquired
      using a 506.9 neutral loss scan and multiple reaction-monitoring (MRM). This
      method can identify all long, medium and short-chain acyl-CoA species in wild
      type mouse liver including predicted 3-hydroxyacyl-CoA species. We validated the
      method using liver of the short-chain-acyl-CoA dehydrogenase (SCAD) knock-out
      mice. As expected, there is a significant increase in [C(4)] butyryl-CoA species
      in the SCAD -/- mouse liver compared to wild type. We then tested the assay in
      liver from the short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD) deficient mice
      to determine the profile of acyl-CoA accumulation in this less predictable model.
      There was more modest accumulation of medium chain species including 3
      hydroxyacyl-CoA's consistent with the known chain-length specificity of the SCHAD
      enzyme.

PMID- 23117084
TI  - [Jogger's nipples].

PMID- 23117086
TI  - Evaluation of the effect of losartan and methotrexate combined therapy in
      adjuvant-induced arthritis in rats.
AB  - There is increasing body of evidence documenting the involvement of angiotensin
      II in inflammatory diseases. Moreover the up-regulation of angiotensin II AT(1)
      receptors in the synovium of rheumatoid arthritis patients has been previously
      described. This study aimed at investigating the anti-inflammatory effect of
      losartan, the selective angiotensin II AT(1) receptor blocker, and comparing the
      efficacy of methotrexate alone and in combination with losartan in adjuvant
      arthritis in rats. Twelve days post adjuvant injection, Sprague-Dawley rats were
      treated with methotrexate (1mg/kg/week), losartan (20mg/kg/day) and their
      combination for 15 days. Severity of arthritis was assessed by hind paw swelling,
      arthrogram scores. Serum was analyzed for measurement of albumin, C-reactive
      protein (CRP), nitrite/nitrate concentrations, interleukin 1beta (IL-1beta),
      tumor necrosis factor-alpha (TNF-alpha), vascular endothelial growth factor
      (VEGF), aspartate transaminase (AST) and alanine transaminase (ALT).
      Histopathological examination was done for hind paws and livers. Methotrexate and
      losartan monotherapies significantly reduced all parameters of inflammation and
      arthritis with better results in the methotrexate group except for the
      transaminases where losartan caused more significant reduction in their serum
      levels. The combined therapy showed better results than methotrexate and losartan
      alone. Hind paws showed better improvement of inflammatory cell infiltration and
      bone resorption in the combined therapy group. Disturbances in liver architecture
      and fibrosis caused by adjuvant arthritis were reverted to normal status in the
      combined therapy group in contrast to losartan and methotrexate monotherapies. In
      conclusion, methotrexate and losartan combined therapy provided more effective
      anti-inflammatory and hepatoprotective effects than either drug alone.

PMID- 23117087
TI  - Cycloart-23-ene-3beta, 25-diol stimulates GLP-1 (7-36) amide secretion in
      streptozotocin-nicotinamide induced diabetic Sprague Dawley rats: a mechanistic
      approach.
AB  - In previous study, we have reported cycloart-23-ene-3beta, 25-diol is an active
      antidiabetic constituent isolated from stem bark of Pongamia pinnata (Linn.)
      Pierre. The objective of the present investigation was to evaluate cycloart-23
      ene-3beta, 25-diol stimulates glucagon like peptide-1 (GLP-1) (7-36) amide
      secretion in streptozotocin-nicotinamide induced diabetic Sprague Dawley rats.
      Molecular docking studies were performed to elucidate the molecular basis for GLP
      1 receptor agonistic activity. Type 2 diabetes was induced in overnight fasted
      Sprague Dawley rats pre-treated with nicotinamide (100mg/kg, i.p.) followed by
      administration of streptozotocin (55 mg/kg, i.p.) 20 min after. The rats were
      divided into following groups; I- non-diabetic, II- diabetic control, III-
      sitagliptin (5mg/kg, p.o.), IV- cycloart-23-ene-3beta, 25-diol (1mg/kg, p.o.).
      The cycloart-23-ene-3beta, 25-diol and sitagliptin treatment was 8 week. Plasma
      glucose was estimated every week (week 0 to week 8). Body weight, food and water
      intake were recorded daily. Glycosylated haemoglobin, lipid profile, plasma and
      colonic active (GLP-1) (7-36) amide, mRNA expression of proglucagnon GLP-1,
      plasma and pancreatic insulin, histology of pancreata as well as biomarkers of
      oxidative stress (superoxidase dismutase, reduced glutathione, malondialdehyde,
      glutathione peroxidase, glutathione S transferase) were measured after 8th week
      treatment. In acute study, active GLP-1 (7-36) amide release, plasma glucose and
      insulin were measured during oral glucose tolerance test. The docking data
      clearly indicated cycloart-23-ene-3beta, 25-diol bind to the GLP-1 receptor. It
      decreased plasma glucose level, increased plasma and pancreatic insulin level as
      well as increased plasma and colonic active GLP-1 (7-36) amide secretion in
      streptozotocin-nicotinamide induced diabetic Sprague Dawley rats.

PMID- 23117088
TI  - Late onset vascular dysfunction in the R6/1 model of Huntington's disease.
AB  - Huntington's disease is a neurodegenerative disorder that also gives raise to
      widespread changes in peripheral organs and tissues. We tested the hypothesis
      that vascular dysfunction may occur in Huntington's disease by studying R6/1 mice
      which express exon 1 of the mutant huntingtin gene. We assessed arterial function
      in R6/1 and wild type (WT) mice using myography. Arterial contractility was
      largely unaltered in R6/1 arteries at 15 and 32 weeks of age. By 40 weeks,
      contractility was impaired irrespective of which vasoconstrictor we tested.
      Endothelium-dependent relaxation was not affected, and we observed no changes in
      arterial geometry or expression of contractile proteins, such as myosin
      regulatory light chains or smooth muscle alpha-actin. The frequency of calcium
      oscillations in R6/1 arterial smooth muscle cells was higher than in WT control
      tissue, whereas myosin phosphorylation was unaltered. Impairment of force by the
      mitochondrial inhibitors cyanide and rotenone was less pronounced in R6/1 than in
      WT arteries and mitochondria were enlarged, in keeping with an effect related to
      altered mitochondrial function. Our results reveal that arteries in the R6/1
      model of Huntington's disease exhibit an age-dependent impairment of
      contractility and that they depend less on mitochondrial function when they
      contract.

PMID- 23117089
TI  - The hypotensive activity and alpha1-adrenoceptor antagonistic properties of some
      aroxyalkyl derivatives of 2-methoxyphenylpiperazine.
AB  - In the search for new hypotesive agents a series of aroxyalkyl derivatives of 2
      methoxyphenylpiperazine was obtained. The aim of the present study was to examine
      their hypotensive properties and to evaluate their mechanism of action. In the
      study their hypotensive activity after i.v. and p.o. administration, influence on
      the pressor responses to adrenaline, noradrenaline and methoxamine, direct
      spasmolytic and vasorelaxant effects were assessed. In the next step two
      compounds which were the most active and selective for alpha(1)-adrenoceptors
      were evaluated for their alpha(1)-adrenoreceptor subtypes selectivity in
      functional bioassays. The data from our experiments indicate that the hypotensive
      activity of tested aroxyalkyl derivatives of 2-methoxyphenylpiperazine is mainly
      a result of their alpha(1)- or alpha(1)/alpha(2)-adrenoceptor blocking
      properties. The two most active compounds showed to be the competitive
      antagonists of alpha(1)-adrenoceptors with stronger activity at alpha(1D)-,
      alpha(1A)- and alpha(1L)- and weaker at alpha(1B)-subtype.

PMID- 23117090
TI  - Anti-tumor effect of germacrone on human hepatoma cell lines through inducing
      G2/M cell cycle arrest and promoting apoptosis.
AB  - Germacrone is one of the main bioactive components in the traditional Chinese
      medicine Rhizoma curcuma. In this study, the anti-proliferative effect of
      germacrone on the human hepatoma cell lines and the molecular mechanism
      underlying the cytotoxicity of germacrone were investigated. Treatment of human
      hepatoma cell lines HepG2 and Bel7402 with germacrone resulted in cell cycle
      arrest and apoptosis in a dose-dependent manner as measured by MTT assay, flow
      cytometric and fluorescent microscopy analysis, while much lower effect on normal
      human liver cell L02 was observed. Flow cytometric analysis revealed that
      germacrone induced G2/M arrest in the cell cycle progression that was associated
      with an obvious decrease in the protein expression of cyclin B1 and its
      activating partner CDK1 with concomitant inductions of p21. Hoechst 33258 and
      Annexin V/PI staining results showed that the total cell number in apoptosis
      associated with a dose-dependent up-regulation of Bax and down-regulation of Bcl
      2/Bcl-xl was increased. In the meantime, the up-regulation of p53 and reactive
      oxygen species increase were observed, which suggested that germacrone might be a
      new potent chemopreventive drug candidate for liver cancer via regulating the
      expression of proteins related to G2/M cell cycle and apoptosis, and p53 and
      oxidative damage may play important roles in the inhibition of human hepatoma
      cells growth by germacrone.

PMID- 23117091
TI  - Evaluation of anti-nociceptive, anti-inflammatory and antipyretic activities of
      Artemisia scoparia hydromethanolic extract.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia scoparia (redstem wormwood) locally
      known as jhahoo or jaukay, is traditionally used in pain, inflammation and
      febrile conditions. So far, little or no scientific work has been reported to
      validate its folk uses in the alleviation of pain, fever and inflammation. The
      present study was designed to explore the analgesic, anti-inflammatory and
      antipyretic effects of the Artemisia scoparia hydromethanolic extract (ASHME),
      and to validate its traditional use in Asia. MATERIALS AND METHODS: This study
      made use of thermal (hot plate induced) and chemical (acetic acid induced)
      nociception models in mice. In addition, the mechanism of antinociception in hot
      plate test was further evaluated in the presence of caffeine (10mg/kg), naloxone
      (2mg/kg) and monosodium glutamate (1g/kg). While carrageenan induced rat paw
      edema and yeast induced mouse pyrexia models were used to test the anti
      inflammatory and antipyretic activities. RESULTS: Administration of single
      intraperitoneal doses (400mg/kg and 800 mg/kg) of ASHME significantly reduced the
      carrageenan induced paw edema in rats (P<0.05, P<0.001) by 54% and 74%, increased
      the thermal nociception time in the hot plate test up to 2- and 2.5-fold (P<0.01,
      P<0.001), inhibited the acetic acid induced writhings in mice by 41.12% and
      61.53% (P<0.001), and attenuated the yeast induced pyrexia in mice by nearly 74%
      and 90% respectively (P<0.01, P<0.001). Caffeine (10mg/kg), naloxone (2mg/kg) and
      monosodium glutamate (1g/kg) significantly (P<0.001) abolished the anti
      nociceptive response of ASHME (400mg/kg). CONCLUSION: These findings suggest that
      the Artemisia scoparia hydromethanolic extract of ASHME possesses anti
      nociceptive, anti-inflammatory and antipyretic potentials, which support its use,
      for the said conditions, in traditional medicine and should be further exploited
      for its use in clinical medicine.

PMID- 23117093
TI  - Appetitive and consummative responding for liquid sucrose in the spontaneously
      hypertensive rat model of attention deficit hyperactivity disorder.
AB  - The spontaneously hypertensive rat (SHR) is one proposed animal model of
      attention deficit hyperactivity disorder (ADHD) argued to show strong face
      validity on the basis of behavioural characteristics. However, SHR may have
      fundamental alterations to the sensitivity of fluid reward due to altered renal
      function that has the potential to affect performance in complex reinforced
      behavioural tests. This could particularly confound determination of operant
      motivational alterations in the SHR. We assessed baseline bodyweight, home cage
      lab chow and water intake in the SHR and their typical control strains: Wistar
      and Wistar Kyoto. We also assessed sucrose preference, and appetitive and
      consummative positive and negative contrast for sucrose (4% versus 20%) on a
      motivational runway. As expected, SHR showed enhanced water intake compared to
      Wistar and Wistar Kyotos but comparable lab chow intake at baseline. SHR
      exhibited sucrose preference for 4% and 20%, as did both control strains, but the
      preference for 4% was enhanced in the SHR. SHR showed significant negative and
      positive contrast in sucrose consumption on the runway, as did Wistar Kyotos.
      Wistars exhibited neither. Appetitive contrast was not measurable in the SHR due
      to a robust locomotor velocity increase at the age of testing. The enhanced fluid
      intake found in the SHR argues against using fluid reinforcers in behavioural
      tests. We suggest the presence of both forms of contrast in the SHR is unusual
      for rats tested in ad lib. food conditions while the contrast pattern in Wistars
      indicate abnormalities in reward sensitivity in this control strain.

PMID- 23117092
TI  - Verbascum xanthophoeniceum-derived phenylethanoid glycosides are potent
      inhibitors of inflammatory chemokines in dormant and interferon-gamma-stimulated
      human keratinocytes.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Verbascum xanthophoeniceum is a representative of
      mullein species with a strong tradition of use in folk medicine as a remedy in
      inflammatory and infectious contexts. This plant accumulates phenylethanoid and
      iridoid metabolites with a partially characterized bioactivity. MATERIALS AND
      METHODS: Here, we compared anti-inflammatory effects of Verbascum
      xanthophoeniceum crude extract, its fractions, isolated iridoid glycosides,
      including aucubin, ajugol, harpagide, harpagoside, nigroside III and nigroside
      VI, and phenylethanoid glycosides verbascoside and forsythoside B in primary
      cultures of normal human keratinocytes (NHK). The gene expression, synthesis, and
      release of soluble pro-inflammatory chemokines, such as IL-8, MCP-1 and IP-10, in
      dormant and IFN-gamma-activated NHK were investigated, and IC(50) for each
      extract/individual substance was determined. RESULTS: We found that the
      phenylethanoid glycosides verbascoside and forsythoside B were effective, dose
      dependent inhibitors of gene expression and de novo synthesis of all the
      chemokines, whereas the iridoid glycosides and phenylpropanoid aglycone
      rosmarinic acid displayed a poor and selective inhibition. Accordingly, the
      fraction of the crude extract containing verbascoside effectively impaired both
      spontaneous and induced chemokine expression in NHK. CONCLUSION: This is the
      first report on the identification of active constituents of Verbascum
      xanthophoeniceum possessing anti-inflammatory properties towards human
      keratinocytes. Phenylethanoid glycosides exerted exquisite corticosteroid-like
      inhibition of pro-inflammatory chemokines at transcriptional and translational
      levels.

PMID- 23117095
TI  - Analysis of the 3'-variable region of the cagA gene from Helicobacter pylori
      strains infecting patients at New York City hospitals.
AB  - Helicobacter pylori infects the gastric mucosa in humans and is a causative agent
      for peptic ulcer disease (PUD) and gastric cancer (GC). CagA is produced by H.
      pylori and is associated with more severe outcomes. cagA genes vary at the 3'
      region with respect to phosphorylation motifs (EPIYA-A, -B, -C, or -D) and CagA
      multimerization motifs (CM). This variability may be associated with the clinical
      outcomes. We examined the variable region of cagA genes expressed in H. pylori
      infected patients treated at three NYC Hospitals. DNA was isolated from gastric
      biopsies of patients undergoing upper endoscopy. Most H. pylori-infected patients
      were Black or Hispanic. The cagA 3'-region of CagA-positive samples was amplified
      by PCR, purified and sequenced. The patterns of EPIYA and CM motifs were examined
      and related to clinical outcomes. We obtained 42 CagA sequences from our sample
      collection. The EPIYA phosphorylation motif pattern was ABC in 81.0% of our
      samples. Western (W) and Eastern (E) CM motifs have also been defined. CagA
      proteins lacking an Eastern CM motif and possessing one or two Western CM motifs
      were observed more frequently in patients with PUD and GC when compared with non
      ulcer gastritis (50.0% vs 11.8%, respectively), suggesting that these CM motif
      patterns are more virulent than those containing at least one Eastern CM motif.
      We conclude that In H. pylori-infected patients treated at NYC Hospitals, CM
      motif patterns in the CagA 30-variable region may be more significant than EPIYA
      motif patterns with respect to clinical outcomes.

PMID- 23117096
TI  - Forefoot angle determines duration and amplitude of pronation during walking.
AB  - The biomechanical mechanisms that link foot structure to injuries of the
      musculoskeletal system during gait are not well understood. This study had two
      parts. The purpose of part one was to determine the relation between clinical
      rearfoot and forefoot angles and foot angles as they make contact with the
      ground. The purpose of part two was to determine the effects of large vs.
      moderate values of both forefoot and rearfoot inversion angles at foot contact on
      foot kinematics. Clinical foot angle, the relationship between the foot and an
      axis extrinsically defined relative to the ground, was calculated from digital
      photographs taken in a prone position. During three speeds of over-ground
      walking, we measured frontal plane rearfoot and forefoot angle relative to the
      ground at foot contact, and the following stance phase kinematic measures:
      amplitude of rearfoot and forefoot eversion, duration of rearfoot and forefoot
      eversion, and duration between heel-off and onset of rearfoot and forefoot
      inversion. We found that the clinical forefoot angle predicted the forefoot angle
      at foot contact. Individuals with a large inversion forefoot angle at contact
      also had greater amplitude of forefoot eversion and everted longer during stance.
      We discuss the possible mechanisms for the increased risk of injury to the hip
      reported for individuals that have a large clinical forefoot angle in non-weight
      bearing. Equally important is the finding that rearfoot angle at contact did not
      predict the motions of the rearfoot or forefoot during stance.

PMID- 23117097
TI  - Does skin stimulation compensate impairments in postural control after ankle
      plantar flexors fatigue?
AB  - It has been suggested that skin stimulation using tape glued to the skin over the
      Achilles tendon helps to improve postural control. It was recently shown that
      these effects might emerge only after muscle fatigue and not during non-fatigue
      standing. Here we tested the influence of skin stimulation on postural control
      before and after fatigue of ankle plantar flexors. Eighteen subjects stood
      quietly on a force plate while the center of pressure was monitored before and
      after fatigue of ankle plantar flexors muscles, with and without medical tape
      glued to the skin over the Achilles tendon. Our results suggested main effects of
      tape stimulation before fatigue (P<.05) and significant effect of tape
      stimulation after fatigue only for amplitude of center of pressure in the
      anteroposterior direction. The novelty of our study is that most of the center of
      pressure variables are improved by skin stimulation when the ankle plantar
      flexors are not fatigued. Therefore the benefits of tape stimulation during
      fatigue condition are questionable.

PMID- 23117098
TI  - [Unusual clinical presentation of a cancer vulva].

PMID- 23117099
TI  - Chemokine profiles in blood associated with delayed asthmatic response to
      allergen challenge.
AB  - BACKGROUND: Patients with bronchial asthma having been challenged with allergen
      develop various types of asthmatic response, such as immediate (IAR), late (LAR)
      or delayed (DYAR) response, due to different immunologic mechanisms. The DYAR,
      beginning 26-32 h, reaching maximum between 32 and 48 h and resolving within 56 h
      after the challenge, differs from IAR and LAR in clinical and immunologic
      features. OBJECTIVES: To investigate the changes in the serum concentrations of
      chemokines associated with the isolated form of DYAR. METHODS: In 22 patients the
      repeated DYAR (p < 0.001) was supplemented with recording of blood cell counts
      and serum concentrations of chemokines before, and up to 72 h after the bronchial
      challenge by means of enzyme-linked immunoassay, (ELISA). RESULTS: The DYAR was
      associated with (a) significantly increased serum concentrations (p < 0.05) of
      CCL 2, CCL 3, CCL 4, CCL 7, CCL 20, CXCL 1, CXCL 8, CXCL 9, CXCL 10 and CXCL 11,
      and (b) significantly decreased serum concentrations, (p < 0.05) of CCL 5, CCL
      11, CCL 17, CCL 22, CCL 24 and CCL 26, as compared with their pre-challenge as
      well as the PBS control values. No significant chemokine changes were recorded
      during the PBS controls (p > 0.1). CONCLUSIONS: These results, together with
      changes in the blood cell counts, provide evidence for an involvement of
      activated Th(1), cells and NK cells (CCL-2, -3, -4, -20, CXCL-9,-10,-11),
      neutrophils (CCL-20, CXCL-1,-8) and monocytes (CCL-2,-3,-4, -7, CXCL-10), upon co
      operation of other cell types, such as epithelial, endothelial and dendritic
      cells, in the immunologic mechanism(s) underlying the DYAR.

PMID- 23117100
TI  - Tailored DVDs: a novel strategy for educating racially and ethnically diverse
      older adults about their medicines.
AB  - INTRODUCTION: The availability of comprehensive and accurate medication history
      information in electronic medical records and through electronic prescribing
      provides the opportunity to create tailored interventions based on individuals'
      particular medication information needs. To meet the challenges of providing
      medication information to low-literate English and Spanish speaking older adults,
      we sought to create individualized, culturally and linguistically inclusive
      medication education materials for older adults from diverse backgrounds.
      METHODS: We used a mixed-method design including a systematic review, analysis of
      existing data, a telephone survey (n=326), and exploratory focus groups
      stratified by race/ethnicity and language spoken (11 focus groups; n=106) to
      identify what information about medications older adults need, want to learn, and
      in what format. We evaluated reactions to three DVDs at low-income senior
      community centers (2 focus groups; n=16). RESULTS: Exploratory focus groups
      provided insights on areas for improvement in patient-provider communication, and
      suggested use of vignettes and testimonials. Upon viewing, participants could
      relate to the testimonials in which actors portrayed people who have problems
      with their medications and were interested in the medication advice presented,
      especially when it was presented by a healthcare professional. DISCUSSION:
      Tailored medication education materials in English and Spanish DVD and print
      material format are suitable for low-literate audiences, acceptable to older
      adults, and feasible to implement using health IT. Virtually all households in
      the United States have a television, with most having a DVD player. DVD segments
      can be used in Internet links, physician office-based television, and consumer
      health IT applications.

PMID- 23117101
TI  - From clinical practice guidelines, to clinical guidance in practice - impacts for
      computerization.
AB  - This paper presents a case study of clinical guidance within oncology clinics.
      Close to all patients treated within the observed clinics were treated according
      to clinical practice guidelines in the form of either a research or a standard
      treatment protocol. The clinical practice guideline artifacts were however rarely
      applied in clinical practice. It was first when the guidelines were translated
      and transformed into second order guiding artifacts (SOGAs) they were applied.
      The SOGAs applied in clinical practice were activity specific holding space for
      relevant documentation. The transformation from clinical practice guideline to
      SOGA was executed according to a standard operating procedure. A wide number of
      physical features were applied to support quick overview and application in
      clinical practice. The clinicians were actively participating in the translation
      and transformation process obtaining ownership to the resulting artifacts. The
      implications for computerization of clinical practice guidelines are discussed. 

PMID- 23117102
TI  - Evidence for building a smarter health and wellness future--key messages and
      collected visions from a joint OECD and NSF workshop.

PMID- 23117103
TI  - A rare case of huge cardiomegaly.

PMID- 23117104
TI  - President's page: the ACC: taking on congenital heart disease and winning!

PMID- 23117105
TI  - Extensive left ventricular hemangioma.

PMID- 23117107
TI  - Yoga for chronic neck pain: a pilot randomized controlled clinical trial.
AB  - Yoga has been found effective in the treatment of chronic low back pain. We aimed
      to evaluate the effectiveness of Iyengar yoga in chronic neck pain by means of a
      randomized clinical trial. Seventy-seven patients (aged 47.9 +/- 7.9, 67 female)
      with chronic neck pain who scored >40 mm on a 100-mm visual analog scale (VAS)
      were randomized to a 9-week Iyengar yoga program with weekly 90-minute classes (n
      = 38) or to a self-care/exercise program (n = 38). Patients were examined at
      baseline and after 4 and 10 weeks. The primary outcome measure was change of mean
      pain at rest (VAS) from baseline to week 10. Secondary outcomes included pain at
      motion, functional disability, quality of life (QOL), and psychological outcomes.
      Twelve patients in the yoga group and 11 patients in the self-care/exercise group
      were lost to follow-up, with higher study nonadherence in the self-care group (5
      versus 10 patients). Mean pain at rest was reduced from 44.3 +/- 20.1 to 13.0 +/-
      11.6 at week 10 by yoga and from 41.9 +/- 21.9 to 34.4 +/- 21.1 by self
      care/exercise (group difference: -20.1, 95% confidence interval: -30.0, -10.1; P
      < .001). Pain at motion was reduced from 53.4 +/- 18.5 to 22.4 +/- 18.7 at week
      10 by yoga and from 49.4 +/- 22.8 to 39.9 +/- 21.5 by self-care/exercise (group
      difference: -18.7, 95% confidence interval: -29.3, -8.1; P < .001). Significant
      treatment effects of yoga were also found for pain-related apprehension,
      disability, QOL, and psychological outcomes. Sensitivity analyses suggested
      minimal influence of dropout rates. Both programs were well tolerated. In this
      preliminary trial, yoga appears to be an effective treatment in chronic neck pain
      with possible additional effects on psychological well-being and QOL. The
      effectiveness of yoga in chronic neck pain should be further tested by
      comparative effectiveness studies with longer observation periods. PERSPECTIVE:
      This article presents the results of a randomized controlled trial on the
      clinical effects of a 9-week yoga program or self-care exercise in patients with
      chronic neck pain. Yoga led to superior pain relief and functional improvements
      and might be a useful treatment option for chronic neck pain.

PMID- 23117106
TI  - Respiratory mechanics measured by forced oscillation technique in combined
      pulmonary fibrosis and emphysema.
AB  - The coexistence of emphysema and pulmonary fibrosis is known as combined
      pulmonary fibrosis and emphysema (CPFE). The aim of this study was to compare the
      lung mechanics measured by multi-frequency forced oscillation technique (FOT)
      among patients with CPFE, interstitial pneumonia (IP), and chronic obstructive
      pulmonary disease (COPD). FOT and pulmonary function tests were performed in 41
      patients with CPFE, 47 with IP, and 86 with COPD. Whole-breath resistance at 20
      Hz was significantly lower in patients with CPFE than in those with IP or COPD,
      irrespective of the severity of airflow limitation. Within-breath analyses of
      resistance revealed no difference among the 3 groups; however, the difference
      between inspiratory and expiratory phases of reactance at 5 Hz, which reflects
      expiratory flow limitation, in patients with CPFE was significantly higher than
      in those with IP and lower than in those with COPD. In conclusion, both emphysema
      and fibrosis affect lung mechanics in CPFE, leading to different findings from IP
      or COPD alone.

PMID- 23117108
TI  - Correlates of higher-dose opioid medication use for low back pain in primary
      care.
AB  - Factors associated with high-dose opioid therapy for noncancer pain are poorly
      understood. We documented the prevalence of high-dose opioid use as well as
      associated demographic, clinical, and health service utilization correlates among
      low back pain patients. Patients prescribed higher doses of opioids (>=100 mg/day
      morphine equivalent at last dispensing; n = 453) and receiving opioids for 90+
      consecutive days were compared to 2 groups: lower-dose opioid group (1-99 mg/day;
      n = 4,815) or no-opioid group (n = 10,184). Higher-dose opioid use occurred in
      2.9% of patients who received any opioids and in 8.6% of patients who received
      opioids long-term. The median dose in the higher-dose group was 180.0 mg/day.
      Compared to the no-opioid group, higher-dose users reported poorer health.
      Compared to either comparison group, patients in the higher-dose group had higher
      rates of mental health and substance use disorders, concurrent sedative-hypnotic
      use (60.5%; n = 274), and health service utilization. After adjusting for select
      covariates, male gender (odds ratio [OR] = 1.68, 95% confidence interval [CI] =
      1.37-2.06), higher comorbidity, Medicare coverage (OR = 1.65, 95% CI = 1.22
      2.23), any mental health or substance use diagnosis (OR = 1.58, 95% CI = 1.28
      1.95), co-prescriptions of sedative-hypnotics (OR = 1.75, 95% CI = 1.42-2.16),
      and more emergency department and specialty pain clinic visits were associated
      with higher likelihood of high-dose prescriptions. PERSPECTIVE: Higher-dose
      opioid therapy is being prescribed to 8.6% of back pain patients who receive long
      term opioids. These patients had higher mental health and medical comorbidities
      and co-prescriptions of sedative-hypnotics, raising potential safety concerns.

PMID- 23117110
TI  - Duodenal carcinoma in a 37-year-old man with Cowden/Bannayan syndrome.
AB  - A 37-year-old man was hospitalised because of anaemia and fatigue due to an
      infiltrating adenocarcinoma of the Treitz angle (duodenum), together with
      gastric, duodenal and colorectal polyps. After the operation, removal of
      colorectal lesions revealed the presence of ganglioneuromatosis of the large
      bowel. Further investigations showed lack of MLH1 protein expression and
      microsatellite instability in the duodenal neoplasm, while the gene was normally
      expressed in the polyps. MLH1 sequence and Multiple Ligation-dependent Probes
      Amplification analysis (from constitutional DNA) were normal. Analysis of the
      PTEN gene revealed the presence of a constitutional mutation (c.510 T>A;
      p.Ser170Arg) which had been associated with the Cowden phenotype. Further
      detailed clinical investigations revealed macrocephaly (63 cm), melanotic spots
      of the penis, small angiomas, millimetric trichilemmomas in the nose and multiple
      lipomas, which led to the diagnosis of Cowden/Bannayan disease. The unusual
      appearance of a duodenal carcinoma as the first symptom rendered the
      identification of the syndrome extremely difficult.

PMID- 23117109
TI  - Signal transduction and modulating pathways in tryptamine-evoked vasopressor
      responses of the rat isolated perfused mesenteric bed.
AB  - Tryptamine is an endogenous and dietary indoleamine-based trace amine implicated
      in cardiovascular pathologies, including hypertension, migraine and myocardial
      infarction. This study aimed at identifying the signalling pathways for the
      vasoconstrictor response to tryptamine in rat isolated perfused mesenteric
      arterial beds and co-released vasodilator modulators of tryptamine-mediated
      vasoconstriction. Tryptamine caused concentration-dependent vasoconstriction of
      the mesenteric bed, measured as increases in perfusion pressure. These were
      inhibited by the 5-HT(2A) receptor antagonist, ritanserin, indicating mediation
      via 5-HT(2A) receptors. The response was inhibited by the phospholipase C (PLC)
      and phospholipase A(2) (iPLA(2)) inhibitors, U-73122 and PACOCF(3), suggesting
      involvement of phospholipase pathways. Activation of these pathways by tryptamine
      releases cyclooxygenase (COX) products since indomethacin (non-selective
      inhibitor of COX-1/2) and nimesulide (selective COX-2 inhibitor) reduced the
      vasoconstriction. The most likely COX vasoconstrictor product was prostaglandin
      PGE(2) since the responses to tryptamine were reduced by AH-6809, a non-selective
      EP(1) receptor antagonist. Involvement of the Rho-kinase pathway in the
      tryptamine-evoked vasoconstriction was also indicated by its reduction by the Rho
      kinase inhibitors, Y-27,632 and fasudil. The tryptamine vasoconstriction is
      modulated by the co-released endothelial vasodilator, nitric oxide. Thus,
      circulating tryptamine can regulate mesenteric blood flow through a cascade of
      signalling pathways secondary to stimulation of 5-HT(2A) receptors.

PMID- 23117113
TI  - [Imaging of hydatid cyst of the lung].
AB  - The pulmonary hydatid cyst is frequent in Mediterranean countries such as
      Morocco. Our analytic study concerned 70 cases of lung hydatid cysts collected
      from 2007 to 2010. Mean age was 35years and we noted a male predominance (53%).
      Forty-seven percent of patients belong to rural environment where 64% of them
      were in contact with dogs. The respiratory symptomatology was made mostly by
      cough (86%) and chest pain (70%). Diagnosis was based on radioclinical arguments
      with positive hydatic serology in some cases. The cyst was single in 84% of the
      cases, safe in 55% of the cases. The location in the right lung was dominant with
      a major affection of the right lower lobe. Conventional surgery was indicated in
      67 cases. The liver hydatid cyst was discovered in 20% of cases and treated at
      the same time phases in 71% of cases. The evolution was good in 73% of the cases
      and marked by a recurrence in three of the operated cases.

PMID- 23117114
TI  - Stimulus level effects on speech-evoked obligatory cortical auditory evoked
      potentials in infants with normal hearing.
AB  - OBJECTIVE: To determine stimulus level effects on speech-evoked cortical auditory
      evoked potentials (CAEPs) in infants for a low (/m/) and high (/t/) frequency
      speech sound. METHODS: CAEPs were recorded for two natural speech tokens, /m/ and
      /t/. Participants were 16 infants aged 3-8months with no risk factors for hearing
      impairment, no parental concern regarding hearing or development, and normal
      tympanograms and otoacoustic emissions. Infants were either tested at levels of
      30, 50, and 70dB SPL or at 40, 60, and 80dB SPL, in counterbalanced order.
      RESULTS: Input-output functions show different effects of increasing sound level
      between stimuli. There were minimal changes in latency with increase in level for
      /t/. For /m/, there were approximately 50-60ms latency increases at soft compared
      to loud levels. Amplitudes saturated at moderate-high levels (60-80dB SPL) for
      both stimuli. CONCLUSIONS: Infants' CAEP input-output functions differ for /t/
      versus /m/ and differ from those previously reported for adults for other
      stimuli. Effects of stimulus and level on CAEPs should be considered when using
      CAEPs for hearing aid or cochlear implant evaluation in infants. SIGNIFICANCE:
      Speech-evoked CAEPs provide an objective measure of central auditory processing.
      Possible differences in CAEP growth between infants and adults suggest
      developmental effects on intensity coding by the auditory cortex.

PMID- 23117111
TI  - Fibroblast cluster formation on 3D collagen matrices requires cell contraction
      dependent fibronectin matrix organization.
AB  - Fibroblasts incubated on 3D collagen matrices in serum or lysophosphatidic acid
      (LPA)-containing medium self-organize into clusters through a mechanism that
      requires cell contraction. However, in platelet-derived growth factor (PDGF)
      containing medium, cells migrate as individuals and do not form clusters even
      though they constantly encounter each other. Here, we present evidence that a
      required function of cell contraction in clustering is formation of fibronectin
      (FN) fibrillar matrix. We found that in serum or LPA but not in PDGF or basal
      medium, cells organized FN (both serum and cellular) into a fibrillar, detergent
      insoluble matrix. Cell clusters developed concomitant with FN matrix formation.
      FN fibrils accumulated beneath cells and along the borders of cell clusters in
      regions of cell-matrix tension. Blocking Rho kinase or myosin II activity
      prevented FN matrix assembly and cell clustering. Using siRNA silencing and
      function-blocking antibodies and peptides, we found that cell clustering and FN
      matrix assembly required alpha5beta1 integrins and fibronectin. Cells were still
      able to exert contractile force and compact the collagen matrix under the latter
      conditions, which showed that contraction was not sufficient for cell clustering
      to occur. Our findings provide new insights into how procontractile (serum/LPA)
      and promigratory (PDGF) growth factor environments can differentially regulate FN
      matrix assembly by fibroblasts interacting with collagen matrices and thereby
      influence mesenchymal cell morphogenetic behavior under physiologic circumstances
      such as wound repair, morphogenesis and malignancy.

PMID- 23117115
TI  - Not just faces... also bodies are "special" but in a different way.

PMID- 23117116
TI  - Reference values in concentric needle electrode studies.

PMID- 23117117
TI  - Depression and recovery of reflex amplitude during electrical stimulation after
      spinal cord injury.
AB  - OBJECTIVE: The aim of this study was to quantify, for the first time, H-reflexes
      evoked during prolonged trains of wide-pulse neuromuscular electrical stimulation
      (WP-NMES) in individuals with chronic spinal cord injury (SCI). We hypothesised
      that after the first H-reflex, reflex amplitudes would be depressed (due to post
      activation depression), but would recover and this recovery would be enhanced
      after a "burst" of 100 Hz WP-NMES. METHODS: Soleus M-waves and H-reflexes evoked
      during WP-NMES (1 ms pulse width) of the tibial nerve were quantified in nine
      individuals with SCI. WP-NMES was delivered in two patterns: "constant-frequency"
      (15 or 20 Hz for 12 s) and "burst-like" (15-100-15 Hz or 20-100-20 Hz; 4 s each
      phase) at an intensity that evoked an M-wave between 10% and 15% of the maximal M
      wave (M(max)). RESULTS: During constant frequency stimulation, after the initial
      depression from the first to the second H-reflex (1st: 57% M(max); 2nd: 25%
      M(max)), H-reflexes did not recover significantly and were 37% M(max) at the end
      of the stimulus train. During the burst-like pattern, after the initial
      depression (1st: 62% M(max); 2nd: 30%), reflexes recovered completely by the end
      of the stimulation (to 55% M(max)) as they were not significantly different from
      the first H-reflex. M-waves were initially depressed (1st: 12% M(max); 2nd: 7%
      M(max)) then did not change throughout the stimulation and were not significantly
      different between stimulation patterns. An analysis of covariance indicated that
      the depression in M-wave amplitude did not account for the depression in H-reflex
      amplitude. CONCLUSIONS: Relatively large H-reflexes were recorded during both
      patterns of NMES. The brief burst of 100 Hz stimulation restored H-reflexes to
      their initial amplitudes, effectively reversing the effects of post-activation
      depression. SIGNIFICANCE: For individuals with chronic SCI, generating
      contractions through central pathways may help reduce muscle atrophy and produce
      contractions that are more fatigue-resistant for rehabilitation, exercise
      programs, or to perform activities of daily living.

PMID- 23117118
TI  - Effective inhibition of metastases and primary tumor growth with CTCE-9908 in
      esophageal cancer.
AB  - BACKGROUND: In spite of multimodular treatment, the therapeutic options for
      esophageal carcinoma are limited, and metastases remain the leading cause of
      tumor-related mortality. Expression of the chemokine receptor CXCR4 significantly
      correlates with poor survival rates in patients with esophageal carcinoma and is
      associated with lymph node and bone marrow metastases. The aim of this study was
      to evaluate the effect of the CXCR4 antagonist CTCE-9908 on metastatic homing and
      primary tumor growth in vitro and in vivo in an orthotopic xenograft model of
      esophageal cancer. MATERIALS AND METHODS: OE19 cells were examined for stromal
      cell-derived factor 1 alpha-mediated migration under CTCE-9908 treatment. The
      CTCE-9908 treatment was further evaluated in an in vitro proliferation assay and
      orthotopic esophageal model, accompanied by magnetic resonance imaging. Tumor and
      metastases were immunohistochemically examined for CXCR4 expression. RESULTS:
      CTCE-9908 has an inhibitory effect on stromal cell-derived factor 1 alpha
      mediated migration and proliferation of OE19 cells. Treatment with CTCE-9908 in
      the orthotopic esophageal model leads to a reduction of metastatic spread and
      primary tumor growth. This was confirmed by magnetic resonsance imaging.
      Treatment with CTCE-9908 results in altered CXCR4 expression pattern exhibiting a
      high degree of variability. CONCLUSION: CTCE-9908 effectively inhibits OE19 cell
      migration and proliferation in vitro, reduces metastases to lung, liver, and
      lymph nodes in vivo, and moreover leads to tumor growth reduction in an
      orthotopic model of esophageal carcinoma.

PMID- 23117119
TI  - Radiographic characterization of prevertebral soft tissue shadow in the
      cervicothoracic region of normal adults.
AB  - BACKGROUND: Many studies have found measurement of prevertebral soft tissue
      shadow (PVSTS) on a lateral cervical radiograph to be a useful indicator of
      cervical spine injury. The purpose of this study is to define, measure, and
      establish a normative set of values for radiographic width of the PVSTS in the
      cervicothoracic region of the spine (C7-T4), using swimmer's view in subjects
      with no trauma to the region. MATERIALS AND METHODS: Radiographic PVSTS widths
      were measured at each vertebral level from C7 to T4 on 131 patients who had
      "normal" radiographic examination (mean age 31.5 y, range 18-58 y). Intra
      observer repeatability was assessed on a random subset of 24 subjects. The range,
      mean, and standard error of these measurements were calculated and documented.
      Stepwise forward regression analysis was conducted on PVSTS data and those
      normalized with respect to the C7 vertebral body width (rPVSTS) to study the
      influences of age, sex, disk level, and tracheal curve shape. RESULTS: Regression
      analysis showed that, in order of influence, the vertebral level, sex, and age
      were three significant factors that affected PVSTS, whereas tracheal curve shape
      was not significant. Similar results were obtained using normalized rPVSTS data,
      with the exception that the influence of sex was not significant in this
      instance. CONCLUSIONS: This study provides a reliable normative database of PVSTS
      in the North American population, and shows that measurement of prevertebral soft
      tissue shadow on a swimmer's view radiograph can be used as a valuable screening
      tool in the evaluation of cervicothoracic spine injury.

PMID- 23117120
TI  - Pneumonia after trauma: a "never event"?

PMID- 23117121
TI  - Commentary on "The pig as a preclinical model for intestinal ischemia-reperfusion
      and transplantation studies".

PMID- 23117122
TI  - The protective effect of adipose-derived stem cells against liver injury by
      trophic molecules.
AB  - BACKGROUND: In this study we investigated whether adipose-derived stem cells
      (ADSCs) had any beneficial protective effects on liver injury and regeneration in
      vivo. Moreover, we examined whether ADSCs protect hepatocytes via trophic
      molecules. MATERIALS AND METHODS: We transplanted ADSCs into mice after 70%
      hepatectomy and ischemia-reperfusion, and observed liver injury and regeneration
      after reperfusion. We co-cultured hepatocytes with ADSCs using a Transwell system
      for 7 d and evaluated the viabilities of hepatocytes and the cytokine levels in
      the culture medium. Bevacizumab was used to confirm the effect of vascular
      endothelial growth factor (VEGF) on hepatocytes. RESULTS: ADSCs improved serum
      liver function at 6 h after reperfusion in a nonlethal model and stimulated liver
      regeneration at 24 h after reperfusion in a lethal model. VEGF levels in the
      culture medium were increased by co-culture ADSCs with hepatocytes. ADSCs
      improved the viabilities of hepatocytes. The inhibited production of VEGF by
      bevacizumab did not affect the viability of hepatocytes. CONCLUSIONS: ADSCs were
      able to ameliorate liver injury and stimulate liver regeneration in subsequent
      hepatectomy and ischemia-reperfusion-injured model mice. Furthermore, hepatocytes
      were protected by the trophic molecules of the ADSCs. However, such protective
      effects might be provided by mechanisms other than VEGF signaling.

PMID- 23117124
TI  - The role of appendectomy for mucinous ovarian neoplasms.
AB  - OBJECTIVE: To determine how frequently the appendix harbors pathology in women
      having surgery for mucinous neoplasms of the ovary and assess the associated
      morbidity. STUDY DESIGN: A retrospective chart review of patients operated on at
      our institution with the diagnosis of a mucinous neoplasm of the ovary or
      appendix. RESULTS: A total of 327 cases were identified. Of the 309 women with
      mucinous ovarian neoplasms, 197 (64%) were benign, 68 (22%) low malignancy
      potential, and 44 (14%) were invasive. Of 155 appendectomies performed, only 1
      metastatic low grade mucinous appendiceal tumor was found, but this appendix was
      grossly abnormal. There was no association between wound complications and
      appendectomy. CONCLUSION: When a grossly normal appendix is removed during
      surgery for a mucinous ovarian neoplasm without evidence of pseudomyxoma
      peritonei, no primary or metastatic mucinous appendiceal tumors are found.

PMID- 23117125
TI  - Defining "phthalates".

PMID- 23117123
TI  - Synthase-dependent exopolysaccharide secretion in Gram-negative bacteria.
AB  - The biosynthesis and export of bacterial cell-surface polysaccharides is known to
      occur through several distinct mechanisms. Recent advances in the biochemistry
      and structural biology of several proteins in synthase-dependent polysaccharide
      secretion systems have identified key conserved components of this pathway in
      Gram-negative bacteria. These components include an inner-membrane-embedded
      polysaccharide synthase, a periplasmic tetratricopeptide repeat (TPR)-containing
      scaffold protein, and an outer-membrane beta-barrel porin. There is also
      increasing evidence that many synthase-dependent systems are post-translationally
      regulated by the bacterial second messenger bis-(3'-5')-cyclic dimeric guanosine
      monophosphate (c-di-GMP). Here, we compare these core proteins in the context of
      the alginate, cellulose, and poly-beta-D-N-acetylglucosamine (PNAG) secretion
      systems.

PMID- 23117127
TI  - Biological insights from hydrogen exchange mass spectrometry.
AB  - Over the past two decades, hydrogen exchange mass spectrometry (HXMS) has
      achieved the status of a widespread and routine approach in the structural
      biology toolbox. The ability of hydrogen exchange to detect a range of protein
      dynamics coupled with the accessibility of mass spectrometry to mixtures and
      large complexes at low concentrations result in an unmatched tool for
      investigating proteins challenging to many other structural techniques. Recent
      advances in methodology and data analysis are helping HXMS deliver on its
      potential to uncover the connection between conformation, dynamics and the
      biological function of proteins and complexes. This review provides a brief
      overview of the HXMS method and focuses on four recent reports to highlight
      applications that monitor structure and dynamics of proteins and complexes, track
      protein folding, and map the thermodynamics and kinetics of protein unfolding at
      equilibrium. These case studies illustrate typical data, analysis and results for
      each application and demonstrate a range of biological systems for which the
      interpretation of HXMS in terms of structure and conformational parameters
      provides unique insights into function. This article is part of a Special Issue
      entitled: Mass spectrometry in structural biology.

PMID- 23117126
TI  - Nicotine related brain activity: the influence of smoking history and blood
      nicotine levels, an exploratory study.
AB  - OBJECTIVE: In this study, we sought to explore brain activity in nicotine
      dependent men in response to acute intravenous nicotine using pharmacological
      magnetic resonance imaging (phMRI). METHODS: phMRI was used to evaluate brain
      activity in response to 1.5 mg/70 kg intravenous nicotine or saline. The nicotine
      and saline were administered on different visits. The time courses of individual
      subjects' nicotine levels were used as regressors to assess neural activity
      relating to the infusions. The influence of smoking history and physiological
      measures on the response to nicotine were also investigated. RESULTS: Greater
      lifetime exposure to cigarette smoking was significantly correlated with higher
      peak serum nicotine levels. PhMRI analysis of the differential response of
      nicotine compared to the saline condition showed distinctive activation patterns
      when analyzed with the (a) nicotine time course, (b) nicotine time course
      controlling for smoking history (pack years), and (c) pack years controlling for
      nicotine. CONCLUSIONS: These results suggest that smoking exposure history
      influences serum nicotine levels and the brain's response to nicotine.
      Alterations in brain activity may be a result of vascular and neuro-adaptations
      involved in drug exposure and addiction.

PMID- 23117129
TI  - The risks of selective serotonin reuptake inhibitor use in infertile women: a
      review of the impact on fertility, pregnancy, neonatal health and beyond.
AB  - STUDY QUESTION: What is the current literature on the safety and efficacy of
      selective serotonin reuptake inhibitor (SSRI) use in infertile women? SUMMARY
      ANSWER: There is little evidence that infertile women benefit from taking an
      SSRI, therefore they should be counseled appropriately about the risks and be
      advised to consider alternate safer treatments to treat depressive symptoms. WHAT
      IS KNOWN ALREADY: SSRI use is associated with possible reduced infertility
      treatment efficacy as well as higher rates of pregnancy loss, preterm birth,
      pregnancy complications, neonatal issues and long-term neurobehavioral
      abnormalities in offspring. STUDY DESIGN, SIZE, DURATION: Review of existing
      literature. PARTICIPANTS/MATERIALS, SETTING, METHODS: We conducted a review of
      all published studies that evaluate females with depressive symptoms who are
      taking antidepressant medications and who are experiencing infertility. MAIN
      RESULTS AND THE ROLE OF CHANCE: Antidepressant use during pregnancy is associated
      with increased risks of miscarriage, birth defects, preterm birth, newborn
      behavioral syndrome, persistent pulmonary hypertension of the newborn and
      possible longer term neurobehavioral effects. There is no evidence of improved
      pregnancy outcomes with antidepressant use. There is some evidence that
      psychotherapy, including cognitive-behavioral therapy as well as physical
      exercise, is associated with significant decreases in depressive symptoms in the
      general population; research indicates that some forms of counseling are
      effective in treating depressive symptoms in infertile women. LIMITATIONS,
      REASONS FOR CAUTION: Our findings are limited by the availability of published
      studies in the field, which are often retrospective and of small size. WIDER
      IMPLICATIONS OF THE FINDINGS: Practitioners who care for infertility patients
      should have a thorough understanding of the published literature so that they can
      adequately counsel their patients. STUDY FUNDING/COMPETING INTEREST(S): None.

PMID- 23117130
TI  - Difficult catheter access to the occluded vessel during endovascular treatment of
      acute ischemic stroke is associated with worse clinical outcome.
AB  - BACKGROUND AND AIM: During endovascular procedures for acute ischemic stroke,
      catheter access to the occluded vessel may be technically difficult or
      impossible. The aim of this study was to access the impact of difficult catheter
      access to target the carotid artery on clinical outcome. METHODS: Anterior
      circulation stroke patients undergoing transfemoral endovascular procedures where
      studied. Patients were divided into four groups according to time from groin
      puncture to target carotid catheterization quartiles. Patients in quartile 4 (Q4)
      were considered difficult carotid access. We defined several outcome measures:
      recanalisation (final Thrombolysis in Cerebral Infarction score >= 2a), time from
      groin puncture to recanalisation and favorable long term outcome (modified Rankin
      Scale score <3 at 3 months). RESULTS: Of 130 patients studied, carotid
      catheterization was impossible in seven patients (5.1%). These patients had
      significantly lower rates of recanalization (14.3% vs 80.5%; p<0.01) and
      favorable outcome (0% vs 36%; p=0.038). Among patients with an accessible carotid
      artery(n=123), median time from groin puncture to carotid catheterization was 20
      min (IQR 10). A negative correlation between time to carotid access and
      recanalization was observed (r=-0.31; p<0.01). Patients in Q4 (>30 min) had lower
      rates of recanalization (60.7% vs 82.4%; p=0.02) and a lower favorable outcome
      (13.6% vs 41.3%; p=0.04). A logistic regression adjusted by age showed that
      baseline National Institutes of Health Stroke Scale score (OR 0.8; 95% CI: 0.72
      to 0.92 p<0.01) and having difficult access (OR 1.3; 95% CI 1.3 to 20.1 p=0.018)
      independently predicted worse long term outcome. CONCLUSIONS: Difficult catheter
      access to target the carotid is common during acute endovascular treatment of
      stroke patients and is associated with a worse clinical outcome. If transfemoral
      access appears difficult, alternative access such as direct carotid puncture
      could be explored.

PMID- 23117128
TI  - Inhibition of sperm capacitation and fertilizing capacity by adjudin is mediated
      by chloride and its channels in humans.
AB  - STUDY QUESTION: Does adjudin disrupt chloride ion (Cl-) ion transport function in
      human sperm and impede sperm capacitation and fertilizing ability in vitro?
      SUMMARY ANSWER: In this study the results indicate that adjudin is a potent
      blocker of Cl- channels: disrupting Cl- ion transport function results in a
      decline in sperm capacitation and fertilizing ability in humans in vitro. WHAT IS
      KNOWN ALREADY: Although our previous studies have demonstrated that adjudin
      exerts its effect by disrupting sertoli-germ cell adhesion junctions, most
      notably apical ectoplasmic specialization by targeting testin and actin filament
      bundles that disrupts the actin-based cytoskeleton in sertoli cells, it remains
      unclear whether adjudin impedes Cl- ion transport function in the human sperm.
      STUDY DESIGN, SIZE AND DURATION: Semen samples were obtained from 45 fertile men
      (aged 25-32). Spermatozoa were isolated from the semen in the human tube fluid
      (HTF) medium by centrifugation through a discontinuous Percoll gradient, and
      incubated with adjudin at 10 nM-10 uM and/or other reagents under capacitating
      conditions for 0-5 h. PARTICIPANTS/MATERIALS, SETTING, METHODS: We evaluated the
      effect of adjudin and different reagents on sperm functions with which they were
      incubated at 37  degrees C. Sperm motility and hyperactivation were analyzed by a
      computer-assisted sperm analysis (CASA) system. Sperm capacitation and the
      acrosome reaction were assessed by chlortetracycline fluorescence staining. Sperm
      fertilizing ability was evaluated by sperm penetration of zona-free hamster egg
      assay, and cellular cAMP levels in spermatozoa were quantified by the EIA kit.
      The proteins tyrosine, serine and threonine phosphorylation in the presence or
      absence of adjudin were analyzed by means of a immunodetection of spermatozoa,
      especially, compared the effect of adjudin on sperm hyperactivation and
      capacitation in the complete HTF medium with the Cl--deficient HTF medium as well
      as the various Cl- channel blockers. MAIN RESULTS AND THE ROLE OF CHANCE: Adjudin
      significantly inhibited sperm hyperactivation but not sperm motility. Adjudin
      induced inhibition of sperm capacitation was reversible, and it was found to
      block the rhuZP3beta- and progesterone-induced acrosome reaction in a dose
      dependent manner. Adjudin also blocked sperm penetration of zona-free hamster
      eggs, and significantly inhibited both forskolin-activated transmembrane adenylyl
      cyclase and soluble adenylyl cyclase activities leading to a significant decline
      in the cellular cAMP levels in human spermatozoa. Adjudin failed to reduce sperm
      protein tyrosine phosphorylation but it did prevent sperm serine and threonine
      protein phosphorylation. Interestingly, adjudin was found to exert its inhibitory
      effects on sperm capacitation and capacitation-associated events only in the
      complete Cl--HTF medium but not Cl--deficient medium, illustrating the likely
      involvement of Cl-. Adjudin inhibits the fertility capacity of human sperm is
      mediated by disrupting chloride ion and its transport function. LIMITATIONS,
      REASONS FOR CAUTION: This study has examined the effect of adjudin only on human
      sperm capacitation and fertilizing ability in vitro and thus has some
      limitations. Further investigations in vivo are needed to confirm adjudin is a
      potent male contraceptive. WIDER IMPLICATIONS OF THE FINDINGS: Our studies
      demonstrated that adjudin inhibition of capacitation is reversible and its
      toxicity is low, opening the door for the examination of adjudin as a mediator of
      male fertility control. Adjudin may be a safe, efficient and reversible male
      antifertility agent and applicable to initial clinical trials of adjudin as a
      male antifertility agent in humans. STUDING FUNDING/COMPETING INTEREST(S): This
      work was supported by the National Basic Research Program of China
      (2006CB504002), the Nature Science Foundation of China (Nos. 81000244 and
      81170554), Zhejiang Project of Science and Technology (2011C23046), the Nature
      Science Fund of Zhejiang province (Nos.Y2100058 and Y2090236), the key Science
      and Technology Innovation Team of Zhejiang Province (No.2012R10048-07) and the
      National Institutes of Health (NICHD U54 HD029990 project 5), USA. The authors
      declare no conflict of interest.

PMID- 23117131
TI  - International multicenter tool to predict the risk of nonsentinel node metastases
      in breast cancer.
AB  - BACKGROUND: Axillary treatment of breast cancer patients is undergoing a paradigm
      shift, as completion axillary lymph node dissections (ALNDs) are being questioned
      in the treatment of patients with tumor-positive sentinel nodes. This study aims
      to develop a novel multi-institutional predictive tool to calculate patient
      specific risk of residual axillary disease after tumor-positive sentinel node
      biopsy. METHODS: Breast cancer patients with a tumor-positive sentinel node and a
      completion ALND from five European centers formed the original patient series (N
      = 1000). Statistically significant variables predicting nonsentinel node
      involvement were identified in logistic regression analysis. A multivariable
      predictive model was developed and validated by area under the receiver operating
      characteristics curve (AUC), first internally in 500 additional patients and then
      externally in 1068 patients from other centers. All statistical tests were two
      sided. RESULTS: Nine tumor- and sentinel node-specific variables were identified
      as statistically significant factors predicting nonsentinel node involvement in
      logistic regression analysis. A resulting predictive model applied to the
      internal validation series resulted in an AUC of 0.714 (95% confidence interval
      [CI] = 0.665 to 0.763). For the external validation series, the AUC was 0.719
      (95% CI = 0.689 to 0.750). The model was well calibrated in the external
      validation series. CONCLUSIONS: We present a novel, international, multicenter,
      predictive tool to assess the risk of additional axillary metastases after tumor
      positive sentinel node biopsy in breast cancer. The predictive model performed
      well in internal and external validation but needs to be further studied in each
      center before application to clinical use.

PMID- 23117133
TI  - The expression of ERalpha, OTR, cPLA(2), COX-2, and PPARgamma in the cervix of
      the ewe during the estrous cycle.
AB  - The ovine cervix relaxes at estrus allowing easier entry of spermatozoa into the
      uterus. The mechanism responsible for this relaxation is not fully elucidated and
      we hypothesized that cervical relaxation at estrus is induced by ovarian and
      pituitary hormones stimulating the local production of prostaglandin E(2) via a
      biosynthetic pathway involving a number of mediators including oxytocin,
      phospholipase A(2) (cPLA(2)), cyclooxygenase-2 (COX-2), and peroxisome
      proliferator-activated receptor gamma (PPARgamma). The aim of this study was to
      investigate the cervical expression of estradiol receptor alpha (ERalpha),
      oxytocin receptor (OTR), cPLA(2), COX-2, and PPARgamma at three stages of the
      estrous cycle (the luteal phase and two times during the follicular phase, just
      before and just after the LH surge). An experiment was conducted during the
      breeding season, in 25 ewes to test this hypothesis. Samples of cervical tissue
      were collected from groups of ewes at three stages of the estrous cycle: the
      luteal (N = 8), "pre-LH surge" (N = 8), and "post-LH surge" (N = 9) stages.
      Cervical tissue from uterine, mid, and vaginal regions of the cervix were
      analyzed by Western immunoblot analysis for ERalpha, OTR, cPLA(2,) COX-2, and
      PPARgamma. The results showed that the levels of all five proteins were lowest
      during the luteal phase of the estrous cycle in all regions of the cervix. The
      levels of all except cPLA(2), increased significantly during the "pre-LH surge"
      stage. The levels of cPLA(2) and ERalpha increased in the "post-LH surge" stage
      and those for OTR and PPARgamma were unchanged and those for COX-2 were lower.
      These data show that the cervical levels of all five of the intermediates in the
      synthesis of prostaglandin E(2) that were examined in this study were higher in
      the "pre-" and "post-LH surge" stages compared with the luteal phase of the
      estrous cycle and these findings are consistent with our hypothesis.

PMID- 23117134
TI  - Effects of caffeine on sperm characteristics after thawing and inflammatory
      response in the uterus after artificial insemination with frozen-thawed boar
      semen.
AB  - We previously reported that AI with frozen-thawed boar semen supplemented with
      caffeine increased the number of uterine sperm by inhibiting migration of
      polymorphonuclear leukocytes (PMNs) into the uterine lumen, and also improved
      fertility of gilts and sows. The objective of the present study was to determine
      the effects of the addition of caffeine to a thawing solution on postthaw sperm
      quality and uterine inflammatory response after AI with frozen-thawed boar semen.
      Incubation of frozen-thawed sperm in Modena solution supplemented with 10 mM
      caffeine for 90 minutes improved (P < 0.05) percentages of progressive motility,
      straightness, and linearity of sperm movement compared with no caffeine, without
      causing damage to plasma or acrosomal membranes. Gilts inseminated once with 2 *
      10(9) frozen-thawed sperm suspended in Modena solution with or without caffeine,
      and gilts that did not receive AI, were slaughtered 4 hours later. Uteri were
      recovered for analysis of number of uterine PMNs and mRNA expression
      (quantitative reverse transcription polymerase chain reaction) of tumor necrosis
      factor-alpha, interleukin (IL)-1beta, IL-6, IL-8, monocyte chemoattractant
      protein-1, and cyclooxygenase 2 in the endometrium. Caffeine decreased (P < 0.05)
      both the number of total uterine PMNs and expression of IL-8 mRNA in the
      endometrium after AI. The amount of IL-8 and cyclooxygenase 2 mRNA after AI in
      the absence of caffeine were higher than samples from gilts that did not receive
      AI (P < 0.05), whereas there were no significant differences between treatments
      in expression levels of tumor necrosis factor-alpha, IL-1beta, IL-6, or monocyte
      chemoattractant protein-1 mRNA. Pregnancy rate in sows inseminated with sperm
      supplemented with caffeine (16 of 23; 70%) tended (P < 0.1) to exceed that
      without caffeine (12 of 26; 46%), but litter size was not affected. In
      conclusion, the addition of caffeine to the thawing solution inhibited migration
      of uterine PMNs, probably by downregulating IL-8 mRNA expression in the
      endometrium.

PMID- 23117132
TI  - Placental development during early pregnancy in sheep: effects of embryo origin
      on fetal and placental growth and global methylation.
AB  - The origin of embryos including those created through assisted reproductive
      technologies might have profound effects on placental and fetal development,
      possibly leading to compromised pregnancies associated with poor placental
      development. To determine the effects of embryo origin on fetal size, and
      maternal and fetal placental cellular proliferation and global methylation,
      pregnancies were achieved through natural mating (NAT), or transfer of embryos
      generated through in vivo (NAT-ET), IVF, or in vitro activation (IVA). On Day 22
      of pregnancy, fetuses were measured and placental tissues were collected to
      immunologically detect Ki67 (a marker of proliferating cells) and 5-methyl
      cytosine followed by image analysis, and determine mRNA expression for three DNA
      methyltransferases. Fetal length and labeling index (proportion of proliferating
      cells) in maternal caruncles (maternal placenta) and fetal membranes (fetal
      placenta) were less (P < 0.001) in NAT-ET, IVF, and IVA than in NAT. In fetal
      membranes, expression of 5-methyl cytosine was greater (P < 0.02) in IVF and IVA
      than in NAT. In maternal caruncles, mRNA expression for DNMT1 was greater (P <
      0.01) in IVA compared with the other groups, but DNMT3A expression was less (P <
      0.04) in NAT-ET and IVA than in NAT. In fetal membranes, expression of mRNA for
      DNMT3A was greater (P < 0.01) in IVA compared with the other groups, and was
      similar in NAT, NAT-ET, and IVF groups. Thus, embryo origin might have specific
      effects on growth and function of ovine uteroplacental and fetal tissues through
      regulation of tissue growth, DNA methylation, and likely other mechanisms. These
      data provide a foundation for determining expression of specific factors
      regulating placental and fetal tissue growth and function in normal and
      compromised pregnancies, including those achieved with assisted reproductive
      technologies.

PMID- 23117135
TI  - A strategy for improvement of postthaw quality of bison sperm.
AB  - The objective was to improve the postthaw quality of bison semen using zwitterion
      (ZI)-based extenders, glycerol addition at a lower temperature (4  degrees C),
      adding reduced glutathione (GSH) in extender, or treating bison sperm with
      cholesterol-loaded cyclodextrin (CLC) before freezing. Postthaw sperm motility
      and structural characteristics were analyzed using a computer-assisted sperm
      analyzer and flow cytometer respectively, at 0 and 3 hours postthaw incubation at
      37  degrees C. In experiment 1, each ejaculate (N = 11) was diluted in Triladyl
      extender (control) or in ZI extenders (Tes-Tris or HEPES-Tris). In addition,
      glycerol in semen was added either at 37  degrees C or 4  degrees C before
      cryopreservation. Extenders had no significant effect on postthaw sperm
      motilities at 0 hour. However, sperm velocity parameters were higher (P < 0.05)
      in ZI extenders than in Triladyl. Sperm population with intact plasma membrane
      (IPM) and acrosomes (IACR) were higher in Triladyl than in ZI extenders (P <
      0.05). Postthaw sperm total and progressive motilities, average path velocity,
      straight-line velocity, IPM, and IPM-IACR did not improve with the addition of
      glycerol at 4  degrees C. In experiment 2, semen was diluted (50 * 10(6) sperm
      per mL) in Triladyl extender containing 0 (control), 0.5, 1.0, or 2.0 mM GSH (an
      antioxidant) at 37  degrees C. Postthaw sperm motility and structural
      characteristics at 0 hour and percentage declined after 3 hour incubation, but
      did not differ because of GSH in the extender (P > 0.05). In experiment 3, fresh
      bison sperm (100 * 10(6) sperm in 1 mL) were pretreated with 0, 1, 2, or 3 mg/mL
      of CLC at 22  degrees C for 15 minutes and diluted to 50 * 10(6) sperm per mL in
      Tris-citric acid-egg yolk-glycerol extender before cryopreservation. The CLC
      pretreated sperm had higher (P < 0.05) postthaw total and progressive motilities,
      IPM, and IACR at 0 hour and less percentage of decline in these characteristics
      after 3 hour postthaw incubation. In conclusion, zwitterion extenders (Tes-Tris
      and HEPES-Tris), temperatures of glycerol addition, and GSH in extender did not
      significantly improve postthaw quality of bison sperm. However, pretreatment with
      CLC significantly improved postthaw quality of bison sperm, which should enhance
      its use in assisted reproductive technologies.

PMID- 23117136
TI  - Influence of assumptions about household waste composition in waste management
      LCAs.
AB  - This article takes a detailed look at an uncertainty factor in waste management
      LCA that has not been widely discussed previously, namely the uncertainty in
      waste composition. Waste composition is influenced by many factors; it can vary
      from year to year, seasonally, and with location, for example. The data publicly
      available at a municipal level can be highly aggregated and sometimes incomplete,
      and performing composition analysis is technically challenging. Uncertainty is
      therefore always present in waste composition. This article performs uncertainty
      analysis on a systematically modified waste composition using a constructed waste
      management system. In addition the environmental impacts of several waste
      management strategies are compared when applied to five different cities. We thus
      discuss the effect of uncertainty in both accounting LCA and comparative LCA. We
      found the waste composition to be important for the total environmental impact of
      the system, especially for the global warming, nutrient enrichment and human
      toxicity via water impact categories.

PMID- 23117137
TI  - Mesocorticolimbic hyperactivity of deprived smokers and brain imaging.
AB  - We determined the association of neuronal circuitry with the desire to smoke by
      acquiring and analyzing functional MRI data. The data were acquired in both
      abstained and subsequently satiated (by 'natural' cigarette smoking) heavy
      smokers and also in demographically and intellectually matched nonsmokers. During
      the acquisition, participants were viewing alternating smoking and nonsmoking
      images that were interleaved by fixation images. From the results, the activities
      in the mesocorticolimbic pathway including the orbitofrontal cortex,
      parahippocampus, hippocampus, and midbrain were significantly negatively
      correlated with carbon monoxide (CO) levels. In contrast, the activities in the
      motor area and the posterior cingulate cortex plus precuneus were significantly
      positively correlated with the CO levels. This is the first study to show that
      mesocorticolimbic and midbrain activities are strongly associated with CO levels,
      and therefore, possibly with smoking desire levels because of the strong
      correlation between CO levels and blood nicotine levels.

PMID- 23117138
TI  - Quicksilver & gold: mercury pollution from artisanal and small-scale gold mining.

PMID- 23117139
TI  - Clinical features and management of intracranial subependymomas in children.
AB  - Subependymoma is a rare low-grade glioma of the central nervous system that
      occurs most commonly in middle-aged and elderly men and rarely in children. Only
      a few paediatric patients with subependymomas have been reported. The authors
      retrospectively analysed five paediatric patients (4 males and 1 female; mean age
      8.6 years; age range 5-13 years) at a single institute from July 1998 to April
      2009 and summarised the clinical characteristics and management of paediatric
      intracranial subependymoma. The most common symptom in these five paediatric
      patients with subependymoma was intracranial hypertension. The tumours were
      located in the fourth ventricle in two patients, in the fourth ventricle with
      extension to the cerebellopontine angle (CPA) in one patient; in the right CPA
      exclusively in one patient, and intraparenchymally in the left parietal lobe in
      one patient, the latter two of which are rare locations for subependymoma.
      Surgery was performed on all five patients. The surgical approach was selected as
      appropriate for the tumor location. Total resection was achieved in three
      patients, and subtotal resection in two. All five patients had good outcomes
      without recurrence. We conclude that surgery is the optimal therapy for
      paediatric patients with intracranial subependymoma.

PMID- 23117140
TI  - Modified C1 lateral mass screw insertion using a high entry point to avoid
      postoperative occipital neuralgia.
AB  - For the past decade, a screw-rod construct has been used commonly to stabilize
      the atlantoaxial joint, but the insertion of the screw through the C1 lateral
      mass (LM) can cause several complications. We evaluated whether using a higher
      screw entry point for C1 lateral mass (LM) fixation than in the standard
      procedure could prevent screw-induced occipital neuralgia. We enrolled 12
      consecutive patients who underwent bilateral C1 LM fixation, with the modified
      screw insertion point at the junction of the C1 posterior arch and the midpoint
      of the posterior inferior portion of the C1 LM. We measured postoperative
      clinical and radiological parameters and recorded intraoperative complications,
      postoperative neurological deficits and the occurrence of occipital neuralgia.
      Postoperative plain radiographs were used to check for malpositioning of the
      screw or failure of the construct. Four patients underwent atlantoaxial
      stabilization for a transverse ligament injury or a C1 or C2 fracture, six
      patients for os odontoideum, and two patients for C2 metastasis. No patient
      experienced vertebral artery injury or cerebrospinal fluid leak, and all had
      minimal blood loss. No patient suffered significant occipital neuralgia, although
      one patient developed mild, transient unilateral neuralgia. There was also no
      radiographic evidence of construct failure. Twenty screws were positioned
      correctly through the intended entry points, but three screws were placed
      inferiorly (that is, below the arch), and one screw was inserted too medially.
      When performing C1-C2 fixation using the standard (Harms) construct, surgeons
      should be aware of the possible development of occipital neuralgia. A higher
      entry point may prevent this complication; therefore, we recommend that the screw
      should be inserted into the arch of C1 if it can be accommodated.

PMID- 23117141
TI  - Craniopharyngioma cell growth is promoted by growth hormone (GH) and is inhibited
      by tamoxifen: involvement of growth hormone receptor (GHR) and IGF-1 receptor
      (IGF-1R).
AB  - Hormone receptors are related to the biological behavior and recurrence of
      craniopharyngioma (CP). The effect of therapeutic growth hormone (GH) replacement
      on CP growth remains largely unclear. We intended to study expression patterns of
      GH-related receptors in CP, and to study the effect of GH and its mediator,
      insulin-like growth factor-1 (IGF-1), as well as tamoxifen, on primary CP cell
      cultures. Primary cell cultures were established from fresh tumor specimens. The
      expression of GH receptor (GHR) and IGF-1 receptor (IGF-1R) in tumor specimens
      was studied using immunohistochemistry. Cell cultures were treated with various
      concentrations of recombinant GH, IGF-1 and tamoxifen. Cell growth promotion or
      inhibition was assayed using the Trypan blue dye exclusion test of cell
      viability. Expression of GHR, IGF-1R, phosphorylated-Akt and Akt after treatment
      was studied using Western blot assay. Twenty-nine primary cultures from 36
      patients were established. GHR and IGF-1R were expressed in tumor tissue. The
      promotion of cell growth by GH compared to control was most prominent at 100
      ng/mL, while inhibition by tamoxifen was concentration dependent. IGF-1 was more
      effective in promoting growth in CP cell cultures with high IGF-1R expression,
      and it increased phosphorylation of Akt protein. Primary cell cultures can be
      established in more than 80% of fresh CP specimens. GH and its endogenous
      mediator, IGF-1, promotes CP cell growth in vitro, while tamoxifen inhibits
      growth.

PMID- 23117142
TI  - A cohort study of patients with anemia on admission and fatality after acute
      ischemic stroke.
AB  - Reduced blood hemoglobin levels may impair oxygen delivery to the brain and
      hinder neurological improvement. We prospectively registered consecutively
      hospitalized Chinese patients with acute ischemic stroke within 24 hours of
      symptom onset to investigate whether anemia on admission influences case fatality
      and functional outcome of acute ischemic stroke at 12 months. Anemia was defined
      as a blood hemoglobin level of < 120 g/L for women, and < 130 g/L for men. We
      also performed a meta-analysis of the current cohort and previously published
      studies. We included 1176 patients, of whom 351 patients (29.8%) had anemia. Age
      (odds ratio [OR]=1.02, 95% confidence interval [CI]: 1.01-1.03), history of
      hemorrhagic stroke (OR=3.34, 95% CI: 1.17-9.56), alcohol consumption (OR=0.59,
      95% CI: 0.38-0.92), and estimated glomerular filtration rate < 60 mL/minute per
      1.73 m(2) (OR=1.34, 95% CI: 1.00-1.80) were the independent predictors of anemia.
      After adjustment for potential confounders, anemia on admission was shown to be
      an independent predictor of death at discharge and at 12 months (OR=1.66, 95% CI,
      1.08-2.56; OR=1.56, 95% CI, 1.05-2.31). A meta-analysis of six included studies
      involving 3810 participants confirmed that anemia on admission was an independent
      predictor of death at the end of follow-up (OR=1.67, 95% CI, 1.25-2.08). Further
      studies are required to confirm these findings.

PMID- 23117144
TI  - The calculations of excited-state properties with Time-Dependent Density
      Functional Theory.
AB  - In this tutorial review, we show how Time-Dependent Density Functional Theory (TD
      DFT) has become a popular tool for computing the signatures of electronically
      excited states, and more specifically, the properties directly related to the
      optical (absorption and emission) spectra of molecules. We discuss the properties
      that can be obtained with widely available programs as well as how to account for
      the environmental effects (solvent and surfaces) and present recent applications
      in these fields. We next expose the transformation of the TD-DFT results into
      chemically intuitive parameters (colours as well as charge-transfer distances).
      Eventually, the non-specialised reader will find a series of advices and warnings
      necessary to perform her/his first TD-DFT calculations.

PMID- 23117143
TI  - The current status and recent advances in high-resolution imaging of spinal
      vascular malformations.
AB  - The management of spinal vascular malformations (SVM) has improved over the last
      four decades with the evolution of imaging, anesthesia, microsurgery, and
      endovascular techniques. Commonly used high-resolution imaging techniques include
      CT angiography, magnetic resonance angiography, and digital subtraction
      angiography. We review the advances that have been made in these imaging
      modalities and discuss their present role for imaging SVM, with the goal of
      assisting neurosurgeons in making judicious use of current imaging techniques to
      develop the most effective management strategies for these complex lesions.

PMID- 23117145
TI  - Endothelialization of chitosan porous conduits via immobilization of a
      recombinant fibronectin fragment (rhFNIII7-10).
AB  - The present study aimed to develop a pre-endothelialized chitosan (CH) porous
      hollowed scaffold for application in spinal cord regenerative therapies. CH
      conduits with different degrees of acetylation (DA; 4% and 15%) were prepared,
      characterized (microstructure, porosity and water uptake) and functionalized with
      a recombinant fragment of human fibronectin (rhFNIII(7-10)). Immobilized
      rhFNIII(7-10) was characterized in terms of amount ((125)I-radiolabelling),
      exposure of cell-binding domains (immunofluorescence) and ability to mediate
      endothelial cell (EC) adhesion and cytoskeletal rearrangement. Functionalized
      conduits revealed a linear increase in immobilized rhFNIII(7-10) with rhFNIII(7
      10) concentration, and, for the same concentration, higher amounts of rhFNIII(7
      10) on DA 4% compared with DA 15%. Moreover, rhFNIII(7-10) concentrations as low
      as 5 and 20MUg ml(-1) in the coupling reaction were shown to provide DA 4% and
      15% scaffolds, respectively, with levels of exposed cell-binding domains
      exceeding those observed on the control (DA 4% scaffolds incubated in a 20MUg ml(
      1) human fibronectin solution). These grafting conditions proved to be effective
      in mediating EC adhesion/cytoskeletal organization on CH with DA 4% and 15%,
      without affecting the endothelial angiogenic potential. rhFNIII(7-10) grafting to
      CH could be a strategy of particular interest in tissue engineering applications
      requiring the use of endothelialized porous matrices with tunable degradation
      rates.

PMID- 23117146
TI  - Electrochemical functionalization of gold and silicon surfaces by a maleimide
      group as a biosensor for immunological application.
AB  - In the present study we investigated the preparation of biofunctionalized
      surfaces using the direct electrochemical grafting of maleimidophenyl molecules
      with subsequent covalent immobilization of specific peptide to detect target
      antibody, thereby extending the application of the biosensing systems towards
      immunodiagnostics. Para-maleimidophenyl (p-MP) functional groups were
      electrochemically grafted on gold and silicon surfaces from solutions of the
      corresponding diazonium salt. A specially synthesized peptide modified with
      cysteine (Cys-peptide) was then immobilized on the p-MP grafted substrates by
      cross-linking between the maleimide groups and the sulfhydryl group of the
      cysteine residues. Accordingly, the Cys-peptide worked as an antigen that was
      able to bind specifically the target antibody (anti-GST antibody), while it was
      non-sensitive to a negative contrast antibody (i.e. anti-Flag beta). The
      immobilization of both specific and non-specific antibodies on the Cys-peptide
      modified surfaces was monitored by infrared spectroscopic ellipsometry, a quartz
      crystal microbalance integrated in flow injection analysis system and
      potentiometric response. The results obtained clearly demonstrated that the
      direct modification of a surface with maleimidophenyl provides a very simple and
      reliable way of preparing biofunctionalized surfaces suitable for the
      construction of immunological biosensors.

PMID- 23117148
TI  - Dose-response analysis of testosterone replacement therapy in patients with
      female to male gender identity disorder.
AB  - Gender identity disorder (GID) is a conflict between a person's actual physical
      gender and the one they identify him or herself with. Testosterone is the key
      agent in the medical treatment of female to male GID patients. We conducted a
      dose-response analysis of testosterone replacement therapy (TRT) in 138 patients
      to determine the onset of the therapeutic effects. The TRT consisted of
      intramuscular injection of testosterone enanthate and patients were divided into
      three groups; 250 mg every two weeks, 250 mg every three weeks and 125 mg every
      two weeks. The onset of deepening of voice, increase in facial hair and cessation
      of menses was evaluated in each group. At one month after the start of TRT, the
      onset of these physical changes was more prevalent in the group receiving the
      higher dose of testosterone, and there were dose-dependent effects observed
      between the three treatment groups. On the other hand, at six months after the
      start of TRT, most of the patients had achieved treatment responses and there
      were no dose-dependent effects with regard to the percentage of patients with
      therapeutic effects. No significant side effects were observed in any of the
      treatment groups. We demonstrated that the early onset of the treatment effects
      of TRT is dose-dependent, but within six months of starting TRT, all three doses
      were highly effective. Current study provides useful information to determine the
      initial dose of TRT and to suggest possible changes that should be made in the
      continuous dosage for long term TRT.

PMID- 23117149
TI  - The relationship between bone marrow characteristics and the clinical prognosis
      of antithyroid drug-induced agranulocytosis.
AB  - This study is aimed to explore the relationship between bone marrow
      characteristics and clinical prognosis of antithyroid drug (ATD) induced
      agranulocytosis. A retrospective study was conducted in the first affiliated
      hospital of the University of South China. A total of 33 hospitalized patients
      diagnosed with ATD-induced agranulocytosis were analyzed. The bone marrow
      characteristics were classified into two types. Type I was characterized by
      reduction or absence of granulocytic precursors and type II was recognized as
      hypercellular bone marrow with dysmaturity of granulocytic cells. Bone marrow of
      20 cases (61%) were characterized with type I whereas 13 cases (39%) with type
      II. The median duration of neutrophil recovery and high-grade fever were 4.7 +/-
      1.0 days and 3.6 +/- 2.5 days respectively for type II, compared to 8.0 +/- 2.8
      days and 8.6 +/- 3.1 days for type I (p < 0.01 in both compared groups). However,
      there was no significant difference between the two types in terms of age, median
      duration of drug administration before the diagnosis of agranulocytosis, the
      amount of neutrophil count on admission and the total administration dose of
      granulocyte-colony stimulating factor (G-CSF) before bone marrow examination. Two
      cases of type I died of complications from infection. This study showed that the
      bone marrow characteristics of ATD-induced agranulocytosis could be classifed
      into two types. Also, the clinical prognosis was closely related to the bone
      marrow features. Type I is the dominant type which is usually associated with
      worse clinical prognosis compared to type II.

PMID- 23117150
TI  - Taming of Ga droplets on DLC layers--size tuning and local arrangement with
      nanometer accuracy.
AB  - A new method for the fabrication of spherical gallium nanoparticles (Ga-NPs) on
      diamond-like carbon (DLC) layers with high precision in their desired diameter
      and positioning is presented. The basic principle is the pre-patterning of a DLC
      film by focused Ga(+) ion beam irradiation and subsequent annealing. During
      thermal treatment the evolution of single Ga-NPs with spherical shape on
      irradiated areas is driven by phase separation and surface segregation of Ga from
      the supersaturated DLC layer. The shape and size of the implanted areas as well
      as the ion fluence serve as a Ga reservoir for the nanoparticle (NP) evolution
      which is strongly correlated with the NP diameter. For the formation of
      segregation seeds to avoid random segregation of the NPs small spots are
      additionally implanted with Ga within the irradiated areas. The NP evolution is
      then assessed with respect to the seed position and the material for the Ga-NP
      growth is gathered from the surrounding reservoir. Using this technique Ga-NPs
      were fabricated with a diameter ranging from 40 nm up to several hundred nm.
      Prospective applications, i.e. in the field of plasmonics, arise from the
      arrangement in chains as well as in periodical two-dimensional arrays with
      defined NP size and interparticle distance.

PMID- 23117151
TI  - Androgen receptor CAG repeat length modifies the effect of 2,3,7,8
      tetrachlorodibenzo-p-dioxin on receptor activity in human prostate cells.
AB  - Increased incidence of prostate cancer has been reported in men exposed to
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD acts through the aryl
      hydrocarbon receptor (AhR), which interacts with the androgen receptor (AR). The
      AR gene contains a polymorphic CAG repeat that influences its transcriptional
      activity. We investigated the influence of TCDD on prostate cancer cells (PC-3)
      and non-tumor prostate cells (PNT1A) on 5alpha-dihydrotestosterone-activated ARs
      containing CAG repeats within normal length range (16, 22, and 28). The AhR
      target gene CYP1A1 mRNA expression was induced by TCDD, but was not affected by
      the AR CAG length. TCDD had no effect on AR activity in PC-3 cells, whereas the
      shortest AR variant was induced by TCDD in PNT1A cells. In conclusion, the CAG
      length dependent effect of TCDD on AR activity in PNT1A, but not in PC-3 cells,
      indicates as a cell-specific effect of TCDD on AR activity.

PMID- 23117152
TI  - Creative innovation with temporal lobe epilepsy and lobectomy.
AB  - OBJECTIVES: Some patients with left temporal degeneration develop visual artistic
      abilities. These new artistic abilities may be due to disinhibition of the visuo
      spatially dominant right hemisphere. Many famous artists have had epilepsy and it
      is possible that some may have had left temporal seizures (LTS) and this left
      temporal dysfunction disinhibited their right hemisphere. Alternatively,
      unilateral epilepsy may alter intrahemispheric connectivity and right anterior
      temporal lobe seizures (RTS) may have increased these artists' right hemisphere
      mediated visual artistic creativity. METHODS: To test the disinhibition versus
      enhanced connectivity hypotheses we studied 9 participants with RTS and 9 with
      left anterior temporal seizures (LTS) who underwent unilateral lobectomy for the
      treatment of medically refractory epilepsy. Creativity was tested using the
      Torrance Test of Creative Thinking (TTCT). RESULTS AND CONCLUSIONS: There were no
      between group differences in either the verbal or figural scores of the TTCT,
      suggesting that unilateral anterior temporal ablation did not enhance visual
      artistic ability; however, for the RTS participants' figural creativity scores
      were significantly higher than verbal scores. Whereas these results fail to
      support the left temporal lobe disinhibition postulate of enhanced figural
      creativity, the finding that the patients with RTS had better figural than verbal
      creativity suggests that their recurrent right hemispheric seizures lead to
      changes in their right hemispheric networks that facilitated visual creativity.
      To obtain converging evidence, studies on RTS participants who have not undergone
      lobectomy will need to be performed.

PMID- 23117153
TI  - An investigation on the cytotoxicity and caspase-mediated apoptotic effect of
      biologically synthesized silver nanoparticles using Podophyllum hexandrum on
      human cervical carcinoma cells.
AB  - Now-a-days synthesis and characterization of silver nanoparticles (AgNPs) through
      biological entity is quite interesting to employ AgNPs for various biomedical
      applications in general and treatment of cancer in particular. This paper
      presents the green synthesis of AgNPs using leaf extract of Podophyllum hexandrum
      Royle and optimized with various parameters such as pH, temperature, reaction
      time, volume of extract and metal ion concentration for synthesis of AgNPs. TEM,
      XRD and FTIR were adopted for characterization. The synthesized nanoparticles
      were found to be spherical shaped with average size of 14 nm. Effects of AgNPs
      were analyzed against human cervical carcinoma cells by MTT Assay, quantification
      of ROS, RT-PCR and western blotting techniques. The overall result indicates that
      AgNPs can selectively inhibit the cellular mechanism of HeLa by DNA damage and
      caspase mediated cell death. This biological procedure for synthesis of AgNPs and
      selective inhibition of cancerous cells gives an alternative avenue to treat
      human cancer effectively.

PMID- 23117154
TI  - Decomposition of proteins by photocatalytic Ti(IV)-doped calcium hydroxyapatite
      particles.
AB  - The decomposition of protein molecules on the surface of Ti(IV)-doped calcium
      hydroxyapatite (TiHap) particles with a Ti/(Ca+Ti) atomic ratio among 0-0.20
      under UV irradiation of 365 nm in wavelength was disclosed. The acidic bovine
      serum albumin (BSA), neutral myoglobin (MGB) and basic lysozyme (LSZ) were
      employed as a model of pathogenic proteins. The photocatalytic activities of
      TiHap particles were estimated from the decomposition of each protein under 1
      mW/cm(2) UV irradiation dispersed in 10 mL quartz tube. The concentrations of
      each protein in the supernatant after centrifugation during the UV irradiation
      were determined both by a HPLC and a SDS-Polyacrylamide Gel Electrophoresis (SDS
      PAGE) analysis methods. No change in BSA concentration ([BSA]) by UV irradiation
      was observed for all the unheated original TiHap particles with low
      photocatalytic activity. The similar results were observed for the systems
      employed heat treated particles endowed a high photocatalytic activity by heat
      treatment at 650 degrees C for 1h. These results indicated that the decomposition
      of BSA molecules is hard to take place. The heme structured MGB molecules are
      decomposed by UV irradiation irrespective of the presence of TiHap particles. In
      the case of heat treated particles, MGB molecules were further decomposed by the
      UV irradiation. The strongest photocatalytic activity was observed for the
      decomposition systems of LSZ by using heat treated particles. In this system, all
      the TiHap particles completely decomposed LSZ molecules after started the UV
      irradiation. It was concluded that the ability of decomposition of proteins is
      strongly related to the molecular weight and rigidity of proteins molecules. The
      LSZ molecule with low molecular weight and rigid structure was easily decomposed
      on the surface of heat treated TiHap particles under UV irradiation.

PMID- 23117156
TI  - Amusics can imitate what they cannot discriminate.
AB  - A longstanding issue in psychology is the relationship between how we perceive
      the world and how we act upon it. Pitch deafness provides an interesting
      opportunity to test for the independence of perception and production abilities
      in the speech domain. We tested eight amusics and eight matched controls for
      their ability to perceive pitch shifts in sentences and to imitate those same
      sentences. Congenital amusics were impaired in their ability to discriminate, but
      not to imitate different intonations in speech. These findings support the idea
      that, when we hear a vocally-imitatable sound, our brains encode it in two
      distinct ways- an abstract code, which allows us to identify it and compare it to
      other sounds, and a vocal-motor code, which allows us to imitate it.

PMID- 23117157
TI  - Probabilistic orthographic cues to grammatical category in the brain.
AB  - What helps us determine whether a word is a noun or a verb, without conscious
      awareness? We report on cues in the way individual English words are spelled,
      and, for the first time, identify their neural correlates via functional magnetic
      resonance imaging (fMRI). We used a lexical decision task with trisyllabic nouns
      and verbs containing orthographic cues that are either consistent or inconsistent
      with the spelling patterns of words from that grammatical category. Significant
      linear increases in response times and error rates were observed as orthography
      became less consistent, paralleled by significant linear decreases in blood
      oxygen level dependent (BOLD) signal in the left supramarginal gyrus of the left
      inferior parietal lobule, a brain region implicated in visual word recognition. A
      similar pattern was observed in the left superior parietal lobule. These findings
      align with an emergentist view of grammatical category processing which results
      from sensitivity to multiple probabilistic cues.

PMID- 23117155
TI  - Sex, race, and the development of acute lung injury.
AB  - BACKGROUND: Prior studies suggest that mortality differs by sex and race in
      patients who develop acute lung injury (ALI). Whether differences in presentation
      account for these disparities remains unclear. We sought to determine whether
      sexual and racial differences exist in the rate of ALI development and ALI
      related mortality after accounting for differences in clinical presentations.
      METHODS: This was a multicenter, observational cohort study of 5,201 patients at
      risk for ALI. Multivariable logistic regression with adjustment for center-level
      effects was used to adjust for potential covariates. RESULTS: The incidence of
      ALI development was 5.9%; in-hospital mortality was 5.0% for the entire cohort,
      and 24.4% for those patients who developed ALI. Men were more likely to develop
      ALI compared to women (6.9% vs 4.7%, P , .001) and had a nonsignificant increase
      in mortality when ALI developed (27.6% vs 18.5%, P 5 .08). However, after
      adjustment for baseline imbalances between sexes these differences were no longer
      significant. Black patients, compared to white patients, presented more
      frequently with pneumonia, sepsis, or shock and had higher severity of illness.
      Black patients were less likely to develop ALI than whites (4.5% vs. 6.5%, P 5
      .014), and this association remained statistically significant after adjusting
      for differences in presentation (OR, 0.66; 95 % CI, 0.45-0.96). CONCLUSIONS: Sex
      and race differences exist in the clinical presentation of patients at risk of
      developing ALI. After accounting for differences in presentation, there was no
      sex difference in ALI development and outcome. Black patients were less likely to
      develop ALI despite increased severity of illness on presentation.

PMID- 23117158
TI  - Analysis of SNARE-mediated membrane fusion using an enzymatic cell fusion assay.
AB  - The interactions of SNARE (soluble N-ethylmaleimide-sensitive factor attachment
      protein receptor) proteins on vesicles (v-SNAREs) and on target membranes (t
      SNAREs) catalyze intracellular vesicle fusion(1-4). Reconstitution assays are
      essential for dissecting the mechanism and regulation of SNARE-mediated membrane
      fusion(5). In a cell fusion assay(6,7), SNARE proteins are expressed ectopically
      at the cell surface. These "flipped" SNARE proteins drive cell-cell fusion,
      demonstrating that SNAREs are sufficient to fuse cellular membranes. Because the
      cell fusion assay is based on microscopic analysis, it is less efficient when
      used to analyze multiple v- and t-SNARE interactions quantitatively. Here we
      describe a new assay(8) that quantifies SNARE-mediated cell fusion events by
      activated expression of beta-galactosidase. Two components of the Tet-Off gene
      expression system(9) are used as a readout system: the tetracycline-controlled
      transactivator (tTA) and a reporter plasmid that encodes the LacZ gene under
      control of the tetracycline-response element (TRE-LacZ). We transfect tTA into
      COS-7 cells that express flipped v-SNARE proteins at the cell surface (v-cells)
      and transfect TRE-LacZ into COS-7 cells that express flipped t-SNARE proteins at
      the cell surface (t-cells). SNARE-dependent fusion of the v- and t-cells results
      in the binding of tTA to TRE, the transcriptional activation of LacZ and
      expression of beta-galactosidase. The activity of beta-galactosidase is
      quantified using a colorimetric method by absorbance at 420 nm. The vesicle
      associated membrane proteins (VAMPs) are v-SNAREs that reside in various post
      Golgi vesicular compartments(10-15). By expressing VAMPs 1, 3, 4, 5, 7 and 8 at
      the same level, we compare their membrane fusion activities using the enzymatic
      cell fusion assay. Based on spectrometric measurement, this assay offers a
      quantitative approach for analyzing SNARE-mediated membrane fusion and for high
      throughput studies.

PMID- 23117159
TI  - Evaluation of a 125I-labelled benzazepinone derived voltage-gated sodium channel
      blocker for imaging with SPECT.
AB  - Voltage-gated sodium channels (VGSCs) are a family of transmembrane proteins that
      mediate fast neurotransmission, and are integral to sustain physiological
      conditions and higher cognitive functions. Imaging of VGSCs in vivo holds promise
      as a tool to elucidate operational functions in the brain and to aid the
      treatment of a wide range of neurological diseases. To assess the suitability of
      1-benzazepin-2-one derived VGSC blockers for imaging, we have prepared a (125)I
      labelled analogue of BNZA and evaluated the tracer in vivo. In an automated patch
      clamp assay, a diastereomeric mixture of the non-radioactive compound blocked the
      Na(v)1.2 and Na(v)1.7 VGSC isoforms with IC(50) values of 4.1 +/- 1.5 MUM and
      0.25 +/- 0.07 MUM, respectively. [(3)H]BTX displacement studies revealed a three
      fold difference in affinity between the two diastereomers. Iodo-destannylation of
      a tin precursor with iodine-125 afforded the two diastereomerically pure tracers,
      which were used to assess binding to VGSCs in vivo by comparing their tissue
      distributions in mice. Whilst the results point to a lack of VGSC binding in
      vivo, SPECT imaging revealed highly localized uptake in the interscapular region,
      an area typically associated with brown adipose tissue, which in addition to high
      metabolic stability of the iodinated tracer, demonstrate the potential of 1
      benzazepin-2-ones for in vivo imaging.

PMID- 23117160
TI  - Hirsutine, an indole alkaloid of Uncaria rhynchophylla, inhibits inflammation
      mediated neurotoxicity and microglial activation.
AB  - Chronic microglial activation endangers neuronal survival through the release of
      various pro-inflammatory and neurotoxic factors. As such, negative regulators of
      microglial activation have been considered as potential therapeutic candidates to
      reduce the risk of neurodegeneration associated with inflammation. Uncaria
      rhynchophylla (U. rhynchophylla) is a traditional oriental herb that has been
      used for treatment of disorders of the cardiovascular and central nervous
      systems. Hirsutine (HS), one of the major indole alkaloids of U. rhynchophylla,
      has demonstrated neuroprotective potential. The aim of the present study was to
      examine the efficacy of HS in the repression of inflammation-induced
      neurotoxicity and microglial cell activation. In organotypic hippocampal slice
      cultures, HS blocked lipopolysaccharide (LPS)-related hippocampal cell death and
      production of nitric oxide (NO), prostaglandin (PG) E2 and interleukin-1beta. HS
      was demonstrated to effectively inhibit LPS-induced NO release from cultured rat
      brain microglia. The compound reduced the LPS-stimulated production of PGE2 and
      intracellular reactive oxygen species. HS significantly decreased LPS-induced
      phosphorylation of the mitogen-activated protein kinases and Akt signaling
      proteins. In conclusion, HS reduces the production of various neurotoxic factors
      in activated microglial cells and possesses neuroprotective activity in a model
      of inflammation-induced neurotoxicity. 

PMID- 23117161
TI  - QRS duration and QRS fractionation on surface electrocardiogram are markers of
      right ventricular dysfunction and atrialization in patients with Ebstein anomaly.
AB  - BACKGROUND: Ebstein anomaly is a rare and heterogeneous congenital heart defect
      affecting the tricuspid valve and right ventricular (RV) myocardium. Few studies
      have analysed the electrocardiographic features of Ebstein anomaly and none has
      addressed correlations with disease severity. METHODS: Patients with Ebstein
      anomaly who had undergone electrocardiography and cardiac magnetic resonance
      (CMR) within 6 weeks between 2001 and 2009 were included. Exclusion criteria
      were: associated congenital cardiac defect, previous RV myoplasty and/or
      reduction surgery, class I anti-arrhythmic drug therapy, and paced/pre-excited
      QRS. Standard electrocardiogram (ECG) findings were correlated with CMR-based RV
      measures and clinical profile. RESULTS: The mean age of the 63 study patients was
      22 +/- 13 years. An RV conduction delay (rsR' pattern in right precordial leads)
      was present in 45 patients (71%). The QRS duration correlated with anatomic RV
      diastolic volume (r = +0.56, P < 0.0001) and inversely with RV ejection fraction
      (EF; r = -0.62, P < 0.0001). The presence of QRS fractionation predicted greater
      atrialized RV volume (80 +/- 31 vs. 45 +/- 37 mL/m(2), P < 0.001). Normal QRS
      duration was associated with smaller anatomic RV diastolic volume (150 +/- 57 vs.
      256 +/- 100 mL/m(2); P < 0.0001), higher RV EF (48 +/- 6 vs. 34 +/- 14%; P <
      0.0001), higher oxygen consumption (VO(2)) at cardiopulmonary exercise (25.8 vs.
      21.8 mL/kg/min, P = 0.05) and lower incidence of oxygen desaturation with
      exercise (25 vs. 65%, P = 0.02). CONCLUSION: Delayed and prolonged depolarization
      of the RV is common in patients with Ebstein anomaly. The QRS duration is a
      marker of RV enlargement and dysfunction. QRS fractionation is associated with a
      greater atrialized RV volume. A preserved surface ECG identifies a subset of
      patients with Ebstein anomaly with mild morphological and functional
      abnormalities and better clinical profile.

PMID- 23117162
TI  - Review of surgical prosthetic paravalvular leaks: diagnosis and catheter-based
      closure.
AB  - Paravalvular leak (PVL) is an uncommon yet serious complication associated with
      surgical prosthetic valve implantation. Paravalvular leak can have significant
      clinical consequence such as congestive heart failure, haemolytic anaemia, and
      infective endocarditis. Recently, transcatheter therapy has been applied to the
      treatment of this disorder with reasonable procedural and clinical success. This
      review discusses the current state of PVLs, the utilization of multi-modality
      imaging in their diagnosis and treatment, and the available therapeutic options.
      Further aim of this review is to examine transcatheter therapy of PVLs including
      the principles, outcomes, and procedural-related complications.

PMID- 23117163
TI  - CCTA to guide revascularization for high-risk CAD: a 'cliff hanger'.

PMID- 23117165
TI  - A cadaveric model for ligamentum teres function: a pilot study.
AB  - PURPOSE: Despite the prevalence and clinical consequences of ligamentum teres
      pathology, its function is poorly understood. The purpose of this study was to
      help define the role the ligamentum teres may have in hip joint stabilization and
      determine whether a ball and string model could be used to describe the function
      of the ligamentum teres. METHODS: Eight embalmed cadavers were dissected to
      remove all soft tissue from around the hip, leaving only the ligamentum teres
      intact. Available hip abduction, adduction, medial rotation, and lateral rotation
      range of motion were measured for three repeated trials. The position of the
      ligamentum teres in relation to the femoral head was recorded at the endpoint
      position of these movements. RESULTS: An endpoint position as limited by the
      ligamentum teres for abduction, medial rotation, and lateral rotation was
      identified at a mean of 73 degrees (SD 11 degrees ), 64 degrees (SD 11 degrees ),
      and 58 degrees (SD 10 degrees ), respectively. Hip adduction was limited by bony
      contact and therefore was not measured. The ligamentum teres wrapped around the
      femoral head to prevent inferior, posterior, and anterior subluxation with
      abduction, medial rotation, and lateral rotation, respectively. Repeated measures
      ANOVA indicated no significant difference in endpoint position based on trial
      number for the three movements (n.s.). CONCLUSION: The ligamentum teres
      consistently tightened to limit hip abduction, medial rotation, and lateral
      rotation. These results support a ball and string model for the femoral head and
      ligamentum teres. This information could be important for those with hip
      instability and ligamentum teres pathology.

PMID- 23117166
TI  - Posterior cruciate-retaining versus posterior stabilized total knee arthroplasty:
      a meta-analysis of randomized controlled trials.
AB  - PURPOSE: To compare the outcomes between posterior cruciate-retaining and
      posterior stabilized total knee arthroplasty (TKA) in order to evaluate which
      approach is superior. METHODS: Randomized controlled trials (RCTs) comparing
      posterior cruciate-retaining with posterior stabilized TKA were reviewed which
      were published up to August 2011. Methodological quality of each included RCT was
      assessed using the Physiotherapy Evidence Database (PEDro) scale. The relevant
      data were analysed using Review Manager 5.1. The Grading of Recommendations
      Assessment, Development and Evaluation (GRADE) approach was used to determine the
      quality of the evidence. RESULTS: Eight RCTs involving 888 patients with 963 knee
      joints met predetermined inclusion criteria. The postoperative range of motion
      (ROM) and flexion angle were 11.07 degrees  and 2.88 degrees  higher for patients
      with a posterior stabilized TKA than those with a posterior cruciate-retaining
      TKA, respectively [weighted mean difference (WMD), -11.07; 95% confidence
      interval (CI), -18.06 to -4.08; p < 0.01 and WMD, -2.88; 95% CI, -5.63 to -0.12;
      p = 0.04]. No statistical differences were observed between the two designs for
      knee society pain score, extension angle, 2- and 5-year knee society score, 2-
      and 5-year knee society function score and complications after primary TKA.
      CONCLUSION: Posterior cruciate-retaining and posterior stabilized TKA have
      similar clinical outcomes with regard to knee function, postoperative knee pain
      and the other complications. Prosthesis survivorship for both posterior cruciate
      retaining and posterior stabilized TKA is satisfactory, and there are no
      differences between them at short- and middle-term follow-up. LEVEL OF EVIDENCE:
      II.

PMID- 23117167
TI  - The treatment of acquired patella baja with proximalize the tibial tuberosity.
AB  - PURPOSE: Acquired patella baja may result in decreased range of motion of the
      knee, extensor lag, and anterior knee pain. The aim of the study was to evaluate
      the efficacy of tibial tubercle osteotomy with proximal displacement. METHODS:
      Between 1998 and 2011, a proximalization of the tibial tuberosity was performed
      in 15 patients (15 knees) with patella baja diagnosed using the Blackburne-Peel
      ratio. Clinical outcomes included the Tegner Lysholm knee scoring scales, the
      WOMAC questionnaire, the short form-12 (SF-12), and a visual analogue score (VAS)
      pain scale. RESULTS: Fifteen proximalizations of the tibial tuberosity were
      performed, with a mean follow-up period of 64 months (5-160). The mean patient
      age was 59 years (41-86 years). The mean preoperative Blackburne-Peel ratio of
      0.4 (0.1-0.6) was improved to a mean of 1.0 (0.8-1.2) post-operatively, which was
      associated with significant improvements in the Lysholm knee scoring scale from
      13.3 +/- 13.0 to 86.7 +/- 10.4 points (p < 0.0001). Quality of life, as measured
      using the SF-12 outcome, also improved significantly (p < 0.0001), as did all
      WOMAC questionnaire score subscales (p < 0.0001). The VAS preoperative status for
      pain improved from 8.3 +/- 2.0 to 1.5 +/- 1.8. No patient had delayed or non
      union of the osteotomy site. CONCLUSIONS: A series of patients with patella baja,
      treated with proximalization of the tibial tuberosity, achieved satisfactory
      outcomes in terms of pain relief and improved function, without major
      complication.

PMID- 23117168
TI  - Is there a role for adult non-cultivated bone marrow stem cells in ACL
      reconstruction?
AB  - PURPOSE: To assess by magnetic resonance imaging (MRI) if adult non-cultivated
      bone marrow stem cells accelerate tendon-to-bone healing in the femoral tunnel,
      after hamstring anterior cruciate ligament (ACL) reconstruction. METHODS: Forty
      three patients underwent ACL reconstruction and were prospectively randomized
      into two groups: 20 patients in the experimental group (group A) with adult non
      cultivated bone marrow stem cells and 23 patients in the control group (group B)
      without adult non-cultivated bone marrow stem cells. All patients underwent MRI
      of the knee at three months after surgery to evaluate the signal-to-noise ratio
      of the interzone. RESULTS: There was no difference in the signal-to-noise ratio
      of the interzone on MRI between the experimental and the control group.
      CONCLUSIONS: Adult non-cultivated bone marrow stem cells do not seem to
      accelerate graft-to-bone healing in ACL reconstruction. The clinical relevance of
      this finding is that adult non-cultivated bone marrow stem cells apparently have
      a limited role in ACL reconstruction.

PMID- 23117169
TI  - Changes in nurses' decision making during a 12-h day shift.
AB  - BACKGROUND: Although shift work is necessary in many health-care settings,
      research suggests that it can have detrimental effects on performance in health
      care providers. AIMS: To determine if a change in decision-making occurred across
      a 12-h day shift in a sample of registered nurses. METHODS: The participants were
      nurses working a 12-h day shift (7 a.m.-7 p.m.) at a large hospital in the south
      eastern USA. Participants completed a policy-capturing questionnaire, examining
      their likelihood of calling a physician in response to specific patient symptoms,
      at the beginning and end of the shift. They also completed self-report surveys on
      alertness, stress and sleepiness. RESULTS: Sixty-five nurses completed the study,
      an overall response rate of 41%. Participants significantly changed their
      decision-making policies from the beginning to the end of the work shift and also
      became significantly less alert and more stressed. However, there was no
      correlation between decision-making and reported alertness and stress.
      CONCLUSIONS: These results suggest that medical judgment in registered nurses
      changed from the beginning to the end of a 12-h day shift. One possible
      underlying mechanism responsible for the changes seen across the shift could be
      the ability to maintain attention, as suggested by the Controlled Attention
      Model. The current results expand upon previous research, indicating there are a
      variety of negative outcomes associated with shift work.

PMID- 23117170
TI  - Synthesis and antimalarial evaluation of a screening library based on a
      tetrahydroanthraquinone natural product scaffold.
AB  - As part of a research program aimed at discovering new antimalarial leads from
      Australian macrofungi a unique fungi-derived prefractionated library was screened
      against a chloroquine-sensitive Plasmodium falciparum line (3D7) using a
      radiometric growth inhibition assay. A library fraction derived from a
      Cortinarius species displayed promising antimalarial activity. UV-guided
      fractionation on the CH(2)Cl(2)/MeOH extract from this fungus resulted in the
      isolation of four known compounds: (1S,3R)-austrocortirubin (1), (1S,3S)
      austrocortirubin (2), 1-deoxyaustrocortirubin (3), and austrocortinin (4).
      Compound 2 was used as a natural product scaffold in the parallel solution-phase
      synthesis of a small library of N-substituted tetrahydroanthraquinones (5-15).
      All compounds (1-15) were tested in vitro against P. falciparum 3D7 parasites and
      (1S,3S)-austrocortirubin (2), the major fungal constituent, was shown to be the
      most active compound with an IC(50) of 1.9 MUM. This compound displayed moderate
      cytotoxicity against neonatal foreskin fibroblast (NFF) cells with an IC(50) of
      15.6 MUM.

PMID- 23117172
TI  - Synthesis and SAR study of 4,5-diaryl-1H-imidazole-2(3H)-thione derivatives, as
      potent 15-lipoxygenase inhibitors.
AB  - A series of 4,5-diaryl-1H-imidazole-2(3H)-thione was synthesized and their
      inhibitory potency against soybean 15-lipoxygenase and free radical scavenging
      activities were determined. Compound 11 showed the best IC(50) for 15-LOX
      inhibition (IC(50) = 4.7 MUM) and free radical scavenging activity (IC(50) = 14
      MUM). Methylation of SH at C(2) position of imidazole has dramatically decreased
      the 15-LOX inhibition and radical scavenging activity as it can be observed in
      the inactive compound 14 (IC(50) >250 MUM). Structure activity similarity (SAS)
      showed that the most important chemical modification in this series was
      methylation of SH group and Docking studies revealed a proper orientation for SH
      group towards Fe core of the 15-LOX active site. Therefore it was concluded that
      iron chelating could be a possible mechanism for enzyme inhibition in this series
      of compounds.

PMID- 23117171
TI  - Synthesis and biological evaluation of 2-substituted-4-(3',4',5'
      trimethoxyphenyl)-5-aryl thiazoles as anticancer agents.
AB  - Antitumor agents that bind to tubulin and disrupt microtubule dynamics have
      attracted considerable attention in the last few years. To extend our knowledge
      of the thiazole ring as a suitable mimic for the cis-olefin present in
      combretastatin A-4, we fixed the 3,4,5-trimethoxyphenyl at the C4-position of the
      thiazole core. We found that the substituents at the C2- and C5-positions had a
      profound effect on antiproliferative activity. Comparing compounds with the same
      substituents at the C5-position of the thiazole ring, the moiety at the C2
      position influenced antiproliferative activities, with the order of potency being
      NHCH(3) > Me >> N(CH(3))(2). The N-methylamino substituent significantly improved
      antiproliferative activity on MCF-7 cells with respect to C2-amino counterparts.
      Increasing steric bulk at the C2-position from N-methylamino to N,N-dimethylamino
      caused a 1-2 log decrease in activity. The 2-N-methylamino thiazole derivatives
      3b, 3d and 3e were the most active compounds as antiproliferative agents, with
      IC(50) values from low micromolar to single digit nanomolar, and, in addition,
      they are also active on multidrug-resistant cell lines over-expressing P
      glycoprotein. Antiproliferative activity was probably caused by the compounds
      binding to the colchicines site of tubulin polymerization and disrupting
      microtubule dynamics. Moreover, the most active compound 3e induced apoptosis
      through the activation of caspase-2, -3 and -8, but 3e did not cause
      mitochondrial depolarization.

PMID- 23117173
TI  - Microwave assisted synthesis and anti-influenza virus activity of 1-adamantyl
      substituted N-(1-thia-4-azaspiro[4.5]decan-4-yl)carboxamide derivatives.
AB  - A microwave-assisted three-component one-pot cyclocondensation method was applied
      for the synthesis of novel N-(1-thia-4-azaspiro[4.5]decan-4-yl)carboxamide
      compounds carrying an adamantyl moiety. The structures of the compounds were
      confirmed by spectral and elemental analysis. All compounds were evaluated for
      antiviral activity against influenza A (H1N1 and H3N2) and influenza B virus in
      MDCK cell cultures. The compounds displayed a confined structure-activity
      relationship. The N-(2,8-dimethyl-3-oxo-1-thia-4-azaspiro[4.5]dec-4-yl)adamantane
      1-carboxamide 3b was the most potent inhibitor [antiviral EC(50): 1.4 MUM against
      influenza A/H3N2 virus]. Its strong inhibitory effect in a virus hemolysis assay
      supports that 3b acts as an influenza virus fusion inhibitor by preventing the
      conformational change of the influenza virus hemagglutinin at low pH.

PMID- 23117174
TI  - 5-(1,3-Benzothiazol-6-yl)-4-(4-methyl-1,3-thiazol-2-yl)-1H-imidazole derivatives
      as potent and selective transforming growth factor-beta type I receptor
      inhibitors.
AB  - A series of 5-(1,3-benzothiazol-6-yl)-4-(4-methyl-1,3-thiazol-2-yl)-1H-imidazole
      derivatives was synthesized as transforming growth factor-beta (TGF-beta) type I
      receptor (also known as activin-like kinase 5 or ALK5) inhibitors. These
      compounds were evaluated for their ALK5 inhibitory activity in an enzyme assay
      and for their TGF-beta-induced Smad2/3 phosphorylation inhibitory activity in a
      cell-based assay. As a representative compound, 16i was a potent and selective
      ALK5 inhibitor, exhibiting a good enzyme inhibitory activity (IC(50) = 5.5 nM) as
      well as inhibitory activity against TGF-beta-induced Smad2/3 phosphorylation at a
      cellular level (IC(50) = 36 nM). Furthermore, the topical application of 3% 16i
      lotion significantly inhibited Smad2 phosphorylation in Mouse skin (90%
      inhibition compared with vehicle-treated animals).

PMID- 23117175
TI  - Microwave assisted solid phase synthesis of highly functionalized N-alkylated
      oligobenzamide alpha-helix mimetics.
AB  - Protein-protein interactions (PPIs) mediate cellular pathways and are implicated
      in numerous aberrant conditions. alpha-Helix mimetics-small molecules that
      reproduce the spatial projection of key residues from an alpha-helix involved in
      a PPI-are attractive generic templates for development of screening libraries,
      however library syntheses of alpha-helix mimetics with diverse functionality are
      less established. This manuscript describes the automated, microwave assisted
      solid phase synthesis based on one such scaffold; an N-alkylated oligobenzamide.

PMID- 23117176
TI  - Cochrane systematic reviews for the mental health field: is the gold standard
      tarnished?
AB  - OBJECTIVE: This study assessed the appropriateness of the Cochrane review system
      for providing guidance to the mental health field regarding evidence-based
      practice. METHODS: Excluding entries for substance misuse and dementia, all
      entries from the three mental health review groups in the 2005-March 2012
      Cochrane database were included (N=552). Entries were coded for review group,
      type (protocol versus review), design (randomized controlled trials or not),
      datedness, percentage of studies excluded, eventual withdrawal, and nature of the
      review's conclusions. RESULTS: A majority (N=322, 58%) of entries focused on
      psychotic, mood, and anxiety disorders. The average Cochrane review was last
      considered up to date in 2006. The reviews excluded over twice as many studies as
      they included, and inclusion of "gray literature" was infrequent. A total of 159
      (44%) reviews reported that there was insufficient evidence to form a conclusion.
      A finding of insufficient evidence to form a conclusion was not related to the
      entry's design but was related to the ratio of excluded to total studies and to
      the use of the Grading of Recommendations Assessment, Development, and Evaluation
      system of evaluating the quality of evidence. CONCLUSIONS: The Cochrane
      Collaboration, an established review system respected globally for its
      methodological rigor, is poised to enlarge its role in guiding the evidence-based
      mental health field. However, addressing issues regarding datedness, diagnostic
      breadth, limited types of evidence, and amount of guidance provided in the
      conclusions would help maximize its contribution to the mental health field.

PMID- 23117177
TI  - The effectiveness of prophylactic ankle braces in reducing the incidence of acute
      ankle injuries in adolescent athletes: a critically appraised topic.
AB  - CLINICAL SCENARIO: Ankle injuries constitute a large number of injuries sustained
      by adolescent athletes participating in high school athletics. Prophylactic ankle
      bracing may be an effective and efficient method to reduce the incidence of ankle
      injuries in adolescent athletes in the secondary-school setting. CLINICAL
      QUESTION: Do prophylactic ankle braces reduce the incidence of acute ankle
      injuries in adolescent athletes? SUMMARY OF KEY FINDINGS: Two of the three
      included studies reported that prophylactic ankle braces reduced the incidence of
      ankle injuries compared with no ankle bracing. CLINICAL BOTTOM LINE: There is
      moderate evidence to support the use of prophylactic ankle braces in adolescent
      athletes, particularly those who participate in football and basketball, to
      reduce the incidence of acute ankle injuries. STRENGTH OF RECOMMENDATION: Grade B
      evidence exists that prophylactic ankle braces reduce the incidence of acute
      ankle injuries in adolescent athletes.

PMID- 23117179
TI  - The breast cancer screening debate: closing a chapter?

PMID- 23117180
TI  - Teenage kicks: cannabis and the adolescent brain.

PMID- 23117178
TI  - The benefits and harms of breast cancer screening: an independent review.
AB  - Whether breast cancer screening does more harm than good has been debated
      extensively. The main questions are how large the benefit of screening is in
      terms of reduced breast cancer mortality and how substantial the harm is in terms
      of overdiagnosis, which is defined as cancers detected at screening that would
      not have otherwise become clinically apparent in the woman's lifetime. An
      independent Panel was convened to reach conclusions about the benefits and harms
      of breast screening on the basis of a review of published work and oral and
      written evidence presented by experts in the subject. To provide estimates of the
      level of benefits and harms, the Panel relied mainly on findings from randomised
      trials of breast cancer screening that compared women invited to screening with
      controls not invited, but also reviewed evidence from observational studies. The
      Panel focused on the UK setting, where women aged 50-70 years are invited to
      screening every 3 years. In this Review, we provide a summary of the full report
      on the Panel's findings and conclusions. In a meta-analysis of 11 randomised
      trials, the relative risk of breast cancer mortality for women invited to
      screening compared with controls was 0.80 (95% CI 0.73-0.89), which is a relative
      risk reduction of 20%. The Panel considered the internal biases in the trials and
      whether these trials, which were done a long time ago, were still relevant; they
      concluded that 20% was still a reasonable estimate of the relative risk
      reduction. The more reliable and recent observational studies generally produced
      larger estimates of benefit, but these studies might be biased. The best
      estimates of overdiagnosis are from three trials in which women in the control
      group were not invited to be screened at the end of the active trial period. In a
      meta-analysis, estimates of the excess incidence were 11% (95% CI 9-12) when
      expressed as a proportion of cancers diagnosed in the invited group in the long
      term, and 19% (15-23) when expressed as a proportion of the cancers diagnosed
      during the active screening period. Results from observational studies support
      the occurrence of overdiagnosis, but estimates of its magnitude are unreliable.
      The Panel concludes that screening reduces breast cancer mortality but that some
      overdiagnosis occurs. Since the estimates provided are from studies with many
      limitations and whose relevance to present-day screening programmes can be
      questioned, they have substantial uncertainty and should be regarded only as an
      approximate guide. If these figures are used directly, for every 10,000 UK women
      aged 50 years invited to screening for the next 20 years, 43 deaths from breast
      cancer would be prevented and 129 cases of breast cancer, invasive and non
      invasive, would be overdiagnosed; that is one breast cancer death prevented for
      about every three overdiagnosed cases identified and treated. Of the roughly
      307,000 women aged 50-52 years who are invited to begin screening every year,
      just over 1% would have an overdiagnosed cancer in the next 20 years. Evidence
      from a focus group organised by Cancer Research UK and attended by some members
      of the Panel showed that many women feel that accepting the offer of breast
      screening is worthwhile, which agrees with the results of previous similar
      studies. Information should be made available in a transparent and objective way
      to women invited to screening so that they can make informed decisions.

PMID- 23117181
TI  - Purification and Identification of antihypertensive peptides in Spanish dry-cured
      ham.
AB  - Novel sequences exhibiting in vitro ACE inhibitory activity as well as in vivo
      antihypertensive activity were identified from Spanish dry-cured ham. Water
      soluble peptide extracts from dry-cured ham were purified by size-exclusion
      chromatography and reversed-phase high performance liquid chromatography and
      then, further identification of sequences was carried out by nano-liquid
      chromatography coupled to tandem mass spectrometry. A total of 73 peptide
      sequences were identified from active fractions presenting 100% homology with
      different Sus scrofa skeletal muscle proteins. All identified peptides showed Mr
      between 374 and 1610 and amino acid sequences between 5 and 14 amino acids in
      length. Considering the low molecular mass and structural requirements for ACE
      inhibition some of the identified peptides were synthesised and their IC(50)
      calculated. The most potent peptide was found to be AAATP (IC(50) value of 100
      MUM). This peptide also showed good in vivo activity because it decreased
      systolic blood pressure by -25.62 +/- 4.5 mmHg (p<0.05) in spontaneous
      hypertensive rats after 8 h administration. Other sequences yielded a moderate
      ACE inhibition. Results from this study show that Spanish dry-cured ham may
      represent a source of natural peptides with potential benefit for human health.

PMID- 23117182
TI  - Hypoxia-induced changes in the zebrafish (Danio rerio) skeletal muscle proteome.
AB  - In this study, patterns of protein expression in zebrafish (Danio rerio) white
      skeletal muscle after 48 h exposure to hypoxia (P(O2)=1.9 kPa) or normoxia
      (P(O2)=18.6 kPa) were evaluated using two-dimensional fluorescence difference gel
      electrophoresis (2D-DIGE). Proteins were separated over two pH ranges in the
      first dimension (pH 4-7 and pH 7-11) prior to separation in the second dimension,
      resolving a total of 821 protein spots. Of these, 77 spots (9.4%) differed
      between hypoxia and normoxia (p <= 0.01), with approximately twice as many
      proteins being higher during hypoxia (56) compared to the number found to be
      higher in normoxic fish (26). Thirty-one protein spots were identified by MALDI
      TOF/TOF mass spectrometry. The expression of several glycolytic enzymes was
      greater in hypoxia than in normoxia, whereas enzymes associated with
      mitochondrial ATP synthesis were lower during hypoxia. Among the more highly up
      regulated proteins during hypoxia were two variants of hemoglobin alpha subunit.
      These patterns of protein expression are consistent with a hypoxic response that
      enhances anaerobic metabolism and O(2) transport to tissues, with a concomitant
      suppression of mitochondrial metabolism. These proteomic changes may contribute
      to the acclimation of zebrafish to hypoxia, thereby increasing their tolerance of
      low oxygen concentrations.

PMID- 23117183
TI  - [Mixed lung tumors: pathological update].
AB  - The pathological diagnosis of lung cancer is based on the WHO classification
      2004. Tumors containing several tumoral contingents are rare but put at the same
      time problems of diagnosis and therapeutic coverage. On biopsy, the diagnosis can
      be refined by using immuno-histochemistry and the recent multidisciplinary
      classification IALSC/ARS/ETS. Some of these tumors can present molecular
      anomalies and therefore are accessible to targeted therapies: the precision of
      the pathological diagnosis is thus essential.

PMID- 23117184
TI  - Photodynamic therapy: an innovative approach to the treatment of keloid disease
      evaluated using subjective and objective non-invasive tools.
AB  - Optimal management for keloid disease (KD) is ill defined, with surgical excision
      resulting in recurrence rates over 50 %. Photodynamic therapy (PDT) uses light to
      activate a photosensitiser localised in diseased tissues. Two recent case studies
      and in vitro studies on keloid-derived fibroblasts indicate potential use of PDT
      in treating KD. Therefore, we hypothesized that there may be a role for PDT in
      the treatment of KD. Twenty KD patients were divided into three groups; existing
      keloid scar, post-surgical debulking and post-total surgical excision. Patients
      underwent three treatments of PDT at weekly intervals. Methyl aminolevulinate
      photosensitiser applied 3 h prior to PDT, administered at 37 J/cm(2). Non
      invasive measures provided quantitative data for pliability, haemoglobin,
      melanin, collagen and flux. Pain and pruritus scores were measured and patients'
      were monitored for KD recurrence. All patients had reduced pain and pruritus
      scores. Haemoglobin flux (p = 0.032), collagen (p = 0.066) and haemoglobin levels
      (p = 0.060) decreased from week 1 to 3 in all except one patient where
      measurements were taken and pliability increased significantly (p = 0.001).
      Increases in pliability were significantly related to decreases in flux (p =
      0.001). Only one patient with a keloid in a stress-prone anatomical location
      experienced recurrence of KD. All other patients had no recurrence at 9-month
      follow-up. Minimal side effects were reported. In conclusion, PDT reduces scar
      formation in KD evidenced by decreased blood flow, increased pliability,
      decreased collagen and haemoglobin levels. These findings indicate potential
      utility of PDT in the treatment of KD.

PMID- 23117186
TI  - Comparison of algae cultivation methods for bioenergy production using a combined
      life cycle assessment and life cycle costing approach.
AB  - Algae are an attractive energy source, but important questions still exist about
      the sustainability of this technology on a large scale. Two particularly
      important questions concern the method of cultivation and the type of algae to be
      used. This present study combines elements of life cycle analysis (LCA) and life
      cycle costing (LCC) to evaluate open pond (OP) systems and horizontal tubular
      photobioreactors (PBRs) for the cultivation of freshwater (FW) or brackish-to
      saline water (BSW) algae. Based on the LCA, OPs have lower energy consumption and
      greenhouse gas emissions than PBRs; e.g., 32% less energy use for construction
      and operation. According to the LCC, all four systems are currently financially
      unattractive investments, though OPs are less so than PBRs. BSW species deliver
      better energy and GHG performance and higher profitability than FW species in
      both OPs and PBRs. Sensitivity analyses suggest that improvements in critical
      cultivation parameters (e.g., CO(2) utilization efficiency or algae lipid
      content), conversion parameters (e.g., anaerobic digestion efficiency), and
      market factors (e.g., costs of CO(2) and electricity, or sale prices for algae
      biodiesel) could alter these results.

PMID- 23117187
TI  - Optimal extraction and hydrolysis of Chlorella pyrenoidosa proteins.
AB  - In this study, for the first time, the applications of two new methods, ionic
      liquid and low-temperature high-pressure cell breakage methods, to the extraction
      of whole proteins in Chlorella pyrenoidosa cells were explored. Meanwhile, the
      comparison with three traditional methods was also made. The results indicated
      that the extraction rate for ionic liquid is only at moderate level, but the new
      low-temperature high-pressure cell breakage method can obviously increase the
      protein extraction rate up to 2- to 15-fold. Subsequently, the hydrolysis of the
      extracted proteins was conducted with three enzymes (papain, trypsin and
      alcalase). The data presented that the degree of hydrolysis for each enzyme under
      the optimal conditions is in the order of: alcalase (18.31%)>papain
      (14.33%)>trypsin (8.47%), demonstrating the potential of C. pyrenoidosa protein
      hydrolysates obtained here in nutritional supplement and medical foods.

PMID- 23117189
TI  - Hierarchical LiFePO4/C microspheres with high tap density assembled by nanosheets
      as cathode materials for high-performance Li-ion batteries.
AB  - In this paper, LiFePO(4)/C microspheres consisting of closely packed nanosheets
      have been synthesized via a simple solvothermal method and a subsequent carbon
      coating procedure. In order to clarify the microstructure of the product, the as
      prepared composite has been characterized by various techniques, such as powder x
      ray diffraction, scanning electron microscopy, energy dispersive spectrum, Raman
      spectroscopy and high-resolution transmission microscopy. Results show that the
      LiFePO(4)/C microspheres are uniform with a particle size of 8-10 MUm. The
      microspheres are composed of densely compacted nanosheets with a thickness of 20
      30 nm. The gaps between the nanosheets are estimated to be 10-50 nm; a carbon
      layer with a thickness of ~4 nm is coated on the surface of the LiFePO(4)
      spheres. The tap density of the LiFePO(4)/C composite reaches up to 1.5 g cm(-3).
      As cathode material for Li-ion batteries, the composite exhibits a high capacity:
      155 mAh g(-1), 144 mAh g(-1), 129 mAh g(-1), and 104 mAh g(-1) at 0.1 C, 1 C, 5 C
      and 10 C, respectively. Furthermore, the material also shows good cycling
      stability at both low and high current rates. The unique nanostructure of the
      material promises its excellent electrochemical properties as a cathode material
      for lithium batteries.

PMID- 23117188
TI  - Efficacy of roflumilast in the COPD frequent exacerbator phenotype.
AB  - BACKGROUND: COPD exacerbations are associated with increased morbidity and
      mortality and can accelerate disease progression. The best predictor of future
      exacerbations is a history of previous exacerbations, which helps identify a
      frequent exacerbator phenotype. This post hoc analysis evaluated the effect of
      roflumilast, a drug known to reduce the COPD exacerbation rate, on exacerbation
      status. METHODS: Pooled data from two 1-year, placebo-controlled, roflumilast
      (500 MUg once daily) studies in patients with symptomatic COPD and severe airflow
      obstruction were evaluated (studies M2-124 and M2-125, ClinicalTrials.gov
      identifiers NCT00297102 and NCT00297115). A total of 3,091 patients were included
      in this analysis (62.5% with GOLD [Global Initiative for Chronic Obstructive Lung
      Disease] III COPD and 29.2% with GOLD 4 COPD). Based on their exacerbation
      frequency status in the previous year, patients were classified as frequent (two
      or more events) or infrequent (fewer than two events) exacerbators. Exacerbation
      frequency was analyzed at baseline and at year 1. RESULTS: Among frequent
      exacerbators treated with roflumilast, 32.0% still had frequent exacerbations at
      year 1 compared with 40.8% of placebo-treated patients (risk ratio, 0.799; P =
      .0148). Among infrequent exacerbators, 17.5% of roflumilast-treated patients
      became frequent exacerbators at year 1 compared with 22.9% of those taking
      placebo (risk ratio, 0.768; P = .0018). The reduction in severe exacerbations
      leading to hospitalization/death was similar between subgroups and occurred
      independently of concomitant long-acting beta2-agonists or previous inhaled
      corticosteroid treatment. When analyzed by severity of airflow limitation, 26.4%
      of roflumilast-treated frequent exacerbators with GOLD III COPD remained frequent
      exacerbators at year 1 compared with 38.9% of those taking placebo (P = .0042).
      CONCLUSIONS: Treatment with roflumilast shifts patients from the frequent to the
      more stable infrequent exacerbator state. TRIAL REGISTRY: ClinicalTrials.gov;
      No.: NCT00297102 and NCT00297115; URL: www.clinicaltrials.gov.

PMID- 23117191
TI  - Lessons of the Elwha River: managing health hazards during dam removal.

PMID- 23117190
TI  - Peptide:MHC tetramer-based enrichment of epitope-specific T cells.
AB  - A basic necessity for researchers studying adaptive immunity with in vivo
      experimental models is an ability to identify T cells based on their T cell
      antigen receptor (TCR) specificity. Many indirect methods are available in which
      a bulk population of T cells is stimulated in vitro with a specific antigen and
      epitope-specific T cells are identified through the measurement of a functional
      response such as proliferation, cytokine production, or expression of activation
      markers(1). However, these methods only identify epitope-specific T cells
      exhibiting one of many possible functions, and they are not sensitive enough to
      detect epitope-specific T cells at naive precursor frequencies. A popular
      alternative is the TCR transgenic adoptive transfer model, in which monoclonal T
      cells from a TCR transgenic mouse are seeded into histocompatible hosts to create
      a large precursor population of epitope-specific T cells that can be easily
      tracked with the use of a congenic marker antibody(2,3). While powerful, this
      method suffers from experimental artifacts associated with the unphysiological
      frequency of T cells with specificity for a single epitope(4,5). Moreover, this
      system cannot be used to investigate the functional heterogeneity of epitope
      specific T cell clones within a polyclonal population. The ideal way to study
      adaptive immunity should involve the direct detection of epitope-specific T cells
      from the endogenous T cell repertoire using a method that distinguishes TCR
      specificity solely by its binding to cognate peptide:MHC (pMHC) complexes. The
      use of pMHC tetramers and flow cytometry accomplishes this(6), but is limited to
      the detection of high frequency populations of epitope-specific T cells only
      found following antigen-induced clonal expansion. In this protocol, we describe a
      method that coordinates the use of pMHC tetramers and magnetic cell enrichment
      technology to enable detection of extremely low frequency epitope-specific T
      cells from mouse lymphoid tissues(3,7). With this technique, one can
      comprehensively track entire epitope-specific populations of endogenous T cells
      in mice at all stages of the immune response.

PMID- 23117192
TI  - Wildlife: the need to better understand the linkages.
AB  - Wildlife are frequently a neglected component of One Health; however, the
      linkages between the health of wildlife and human, domestic animal, and
      environmental health are clear. The majority of emerging zoonotic diseases are
      linked to wildlife, primarily driven by anthropogenic land changes. Despite this
      risk, wildlife have important links to people as environmental indicators, food
      security and safety, and through human livelihoods. This chapter will describe
      these linkages and demonstrate the need to understand these linkages through
      targeted surveillance and understanding the ecology of wildlife diseases. While
      the management of wildlife diseases presents a significant challenge, such
      practices will greatly improve the health of people, domestic animals, wildlife
      and the environment. 

PMID- 23117193
TI  - Synthesis of allenamides by Pd-catalyzed coupling of 3-alkoxycarbonyloxy ynamides
      or 1-alkoxycarbonyloxy allenamides with arylboronic acids.
AB  - An efficient palladium-catalyzed method is reported for the synthesis of multi
      substituted allenamides by Suzuki-Miyaura cross-coupling reaction between easily
      prepared 3-alkoxycarbonyloxy ynamides or 1-alkoxycarbonyloxy allenamides and
      arylboronic acids.

PMID- 23117194
TI  - Incorporating different secondary building units of {Bi2}, {Bi8} and {Bi10} to
      construct diversity of luminescent bismuth-organic frameworks.
AB  - Three new bismuth-organic compounds, namely, Bi(OH)(2,6-pdc).H(2)O (1),
      Bi(4)(OH)(4)(2,6-pdc)(4)(H(2)O)(3).H(2)O (2) and Bi(5)(OH)(5)(2,6
      pdc)(5)(H(2)O)(4).H(2)O (3) (2,6-H(2)pdc = pyridine-2,6-dicarboxylate) have been
      obtained by incorporating different Bi subunits as building blocks under
      hydrothermal conditions. Compound 1 contains dimeric {Bi(2)} units and these are
      further linked by 2,6-pdc(2-) ligands into a 2D net with 3(6) topology. Compounds
      2-3 display 4(4) net topology by using linear {Bi(8)} and {Bi(10)} as secondary
      building units (SBUs), respectively. Compounds 1-3 display yellow and blue
      luminescence, respectively. Furthermore, the PXRD, TGA, UV-visible and IR spectra
      of 1-3 were also studied.

PMID- 23117195
TI  - Detection of IL-6 by magnetic nanoparticles grown with the assistance of mid
      infrared lighting.
AB  - Nanomedical systems have attracted considerable attention primarily due to
      suitability in applications for specific cell selection through biomolecular
      targeting and rare cell detection enhancement in a diverse, multicellular
      population. In the present study, magnetic nanoparticles were prepared for use in
      high accuracy cell sensing. Magnetic nanoparticle growth was assisted by mid
      infrared lighting. By this mechanism, a narrow window, estimated to be 2%, was
      achieved for the dimension distribution of grown nanoparticles. Combined with
      silicon nanowire (SiNW) transistors, a sensor with ultra high sensitivity for the
      detection of specific potential low abundance biomarkers has been achieved, which
      has been specifically used to detect interleukin-6 (IL-6) at extremely low
      concentrations. A novel biosensor with high sensitivity has been fabricated and
      utilized in the detection of IL-6 at 75 fM to 50 pM. The system consists of an
      SiNW transistor and magnetic nanoparticles with even dimension distribution. The
      novel sensor system is suitable for quantifying IL-6 at low concentrations in
      protein samples. 

PMID- 23117196
TI  - Application of dynamic susceptibility contrast-enhanced perfusion in temporal
      lobe epilepsy.
AB  - BACKGROUND: Accurately locating the epileptogenic focus in temporal lobe epilepsy
      (TLE) is important in clinical practice. Single-photon emission computed
      tomography (SPECT) and positron-emission tomography (PET) have been widely used
      in the lateralization of TLE, but both have limitations. Magnetic resonance
      perfusion imaging can accurately and reliably reflect differences in cerebral
      blood flow and volume. PURPOSE: To investigate the diagnostic value of dynamic
      susceptibility contrast-enhanced (DSC) perfusion magnetic resonance imaging (MRI)
      in the lateralization of the epileptogenic focus in TLE. MATERIAL AND METHODS:
      Conventional MRI and DSC-MRI scanning was performed in 20 interictal cases of TLE
      and 20 healthy volunteers. The relative cerebral blood volume (rCBV) and relative
      cerebral blood flow (rCBF) of the bilateral mesial temporal lobes of the TLE
      cases and healthy control groups were calculated. The differences in the
      perfusion asymmetry indices (AIs), derived from the rCBV and rCBF of the
      bilateral mesial temporal lobes, were compared between the two groups. RESULTS:
      In the control group, there were no statistically significant differences between
      the left and right sides in terms of rCBV (left 1.55 +/- 0.32, right 1.57 +/-
      0.28) or rCBF (left 99.00 +/- 24.61, right 100.38 +/- 23.46) of the bilateral
      mesial temporal lobes. However, in the case group the ipsilateral rCBV and rCBF
      values (1.75 +/- 0.64 and 96.35 +/- 22.63, respectively) were markedly lower than
      those of the contralateral side (2.01 +/- 0.79 and 108.56 +/- 26.92; P < 0.05).
      Both the AI of the rCBV (AI(rCBV); 13.03 +/- 10.33) and the AI of the rCBF
      (AI(rCBF); 11.24 +/- 8.70) of the case group were significantly higher than that
      of the control group (AI(rCBV) 5.55 +/- 3.74, AI(rCBF) 5.12 +/- 3.48; P < 0.05).
      The epileptogenic foci of nine patients were correctly lateralized using the 95th
      percentile of the AI(rCBV) and AI(rCBF) of the control group as the normal upper
      limits. CONCLUSION: In patients with TLE interictal, both rCBV and rCBF of the
      ipsilateral mesial temporal lobe were markedly lower than that of healthy control
      subjects. DSC-MRI can provide lateralization for TLE.

PMID- 23117197
TI  - Evaluation of left renal vein entrapment using multidetector computed tomography.
AB  - BACKGROUND: Nutcracker syndrome, also called left renal vein entrapment syndrome,
      is a cause of non-glomerular hematuria with difficulties in diagnosis.
      Multidetector computed tomography (MDCT) is a powerful tool to prevent
      unnecessary diagnostic procedures. PURPOSE: To retrospectively determine the
      prevalence of nutcracker phenomenon and nutcracker syndrome seen in MDCT in
      consecutive patients. MATERIAL AND METHODS: The institutional review board
      approved the study and waived the requirement for informed consent. Abdominal
      contrast-enhanced MDCT scans were reviewed from 1000 consecutive patients. MDCT
      scan assessment included renal vein diameter measurements and evaluation for the
      presence of anterior or posterior left renal vein entrapment. Electronic medical
      records and urine analysis reports of patients with left renal vein entrapment
      were reviewed. Student's t test was used to assess differences in renal vein
      diameter in patients with left renal vein entrapment. RESULTS: Left renal vein
      entrapment was observed in 10.9% (109), retro-aortic left renal vein in 6.5%
      (65), entrapment of left renal vein between superior mesenteric artery and aorta
      in 4.1% (41), and circumaortic left renal vein in 0.3% (3) of patients. Mean
      diameters of right (8.8 +/- 1.9 mm) and unentrapped left (8.9 +/- 1.8 mm) renal
      veins were not significantly different (P = 0.1). The mean diameter of anterior
      entrapped left renal veins (10.3 +/- 2 mm) was significantly greater (P = 0.04)
      than contralateral renal veins (8.6 +/- 2.1 mm) in their widest portion. In 8.8%
      of patients with the left renal vein entrapment, urine analysis showed isomorphic
      hematuria or proteinuria with no other known cause. Varicocele and pelvic
      congestion were seen in 5.5% of patients with the left renal vein entrapment.
      CONCLUSION: Left renal vein entrapment is not a rare entity and renal nutcracker
      phenomenon might be underdiagnosed.

PMID- 23117198
TI  - Postoperative appearances of esophageal atresia repair: retrospective study of
      210 patients with review of literature - what the radiologist should know.
AB  - BACKGROUND: Primary surgical repair forms the definitive treatment of esophageal
      atresia. Long-term survival rates and patient morbidity after repair still
      remains a problem especially in developing countries. Postoperative morbidity
      depends on the incidence of anastomotic leak, gastroesophageal reflux,
      strictures, and recurrent fistula formation. PURPOSE: To describe the frequency
      of different findings at fluoroscopic evaluation of postoperative esophagus in
      children following repair for esophageal atresia with or without tracheo
      esophageal fistula. MATERIAL AND METHODS: Hospital records and upper
      gastrointestinal contrast studies of 210 patients following repair for esophageal
      atresia with or without a tracheo-esophageal fistula were reviewed by two
      pediatric radiologists. All children underwent surgery in the first few days of
      life (days 1-6). Fluoroscopic contrast study was performed at various intervals
      after surgery in children with suspected complications or feeding difficulties.
      RESULTS: Images from upper gastrointestinal contrast studies of 210 patients (126
      boys, 84 girls) were evaluated and recorded. Findings were recorded as normal
      postoperative appearances (37.1%) and complications/sequelae, which included
      strictures (33.8%), minor and major leaks (11.9%), reflux (13.8%), motility
      problems (7.1%), persistent fistula (3.8%), diverticulae formation (4.7%), and
      hiatus hernia (2.1%). CONCLUSION: Strictures, leaks, and reflux are the most
      common complications of esophageal atresia repair. Knowledge of various
      postoperative appearances would be useful for planning an appropriate management
      strategy in these children.

PMID- 23117199
TI  - Therapeutic Window for Striatal Dopamine D2/3 Receptor Occupancy in Older
      Patients With Schizophrenia:  A Pilot PET Study.
AB  - OBJECTIVE:: In younger patients with schizophrenia, positron emission tomography
      (PET) studies have identified a therapeutic window of striatal dopamine D2/3
      receptor occupancy of 65%-80%. This type of empirical information is not
      available in late life. Our primary aim was to assess the effect of changes in
      D2/3 relative receptor occupancy (RRO) on clinical outcomes in this population.
      DESIGN:: Open-label intervention. SETTING:: Centre for Addiction and Mental
      Health, Toronto. PARTICIPANTS:: Subjects with schizophrenia age 50 years or more
      who were clinically stable and previously maintained on oral risperidone for more
      than 6 months. INTERVENTION:: A dose reduction of risperidone of up to 40%,
      followed by a 3-month follow-up. MEASUREMENTS:: Dopamine D2/3 RRO in dorsal
      putamen was assessed, using the region of interest analysis of [C]raclopride PET
      scans, before and after the dose reduction. Clinical assessments included the
      Positive and Negative Syndrome Scale and the Simpson-Angus Scale. RESULTS:: Nine
      subjects (mean +/- SD age: 58 +/- 7 years; mean +/- SD baseline risperidone dose:
      3.4 +/- 1.6 mg/day) participated in the study. Extrapyramidal symptoms (EPS) were
      present in six subjects and were associated with 70% or more D2/3 RRO in the
      putamen (range: 70%-87%). Following the dose reduction, EPS resolved in five
      subjects. Two subjects experienced a clinical worsening at 52% and at less than
      50% D2/3 RRO. CONCLUSION:: EPS diminished less than 70% D2/3 RRO, which suggests
      a lower therapeutic window for older patients with schizophrenia than that for
      younger patients. Although these findings have to be replicated in a larger
      sample, they have important implications for future drug development and clinical
      guidelines in late-life schizophrenia.

PMID- 23117200
TI  - Relative survivability of human osteoblasts is enhanced by 39  degrees C and
      ascorbic acid after exposure to photopolymerization ingredients.
AB  - Photopolymerizable hydrogels offer great potential in cartilage tissue
      engineering due to their ability to conform to irregular defect shapes and be
      applied in a potentially minimally invasive manner. An important process
      requirement in the use of photopolymerizable hydrogels is the ability of the
      suspended cells to withstand low intensity ultraviolet light (UV) exposure (4-5
      mW/cm(2)) and photoinitiator concentrations. For cartilage integration with
      underlying subchondral bone tissue, robust localized osteoblast activity is
      necessary. Yet, while it is known that osteoblasts do not respond well to UV
      light, limited work has been conducted to improve their survivability. In this
      study, we evaluated the cellular cytotoxicity of five different human cell
      sources at different UV exposure times, with and without a commercially used
      photoinitiator. We were able to confirm that human osteoblasts were the least
      tolerant to varying UV exposure times in comparison to bone marrow stem cell,
      periodontal ligament cell, smooth muscle and endothelial cell lineages. Moreover
      osteoblasts cultured at 39  degrees C did not deteriorate in terms of alkaline
      phosphatase expression or calcium deposition within the extracellular matrix
      (ECM), but did reduce cell proliferation. We believe however that the lower
      proliferation diminished osteoblast sensitivity to UV and the photoinitiator. In
      fact, the relative survivability of osteoblasts was found to be augmented by the
      combination of a biochemical factor and an elevated incubation temperature;
      specifically, the use of 50 mg/l of the anti-oxidant, ascorbic acid significantly
      (P < 0.05) increased the survivability of osteoblasts when cultured at 39 
      degrees C. We conclude that ascorbic acid at an incubation temperature of 39 
      degrees C can be included in in vitro protocols used to assess cartilage
      integration with bone ECM. Such inclusion will enhance conditions of the
      engineered tissue model system in recapitulating in vivo osteoblast activity. 

PMID- 23117201
TI  - Entanglement of grey seals Halichoerus grypus at a haul out site in Cornwall, UK.
AB  - Entanglement in marine debris has been internationally recognised as a potential
      threat to marine species. Sightings records and a photo identification catalogue
      from a haul out site in southwest England were used to establish entanglement
      records for grey seals Halichoerus grypus. Between 2004 and 2008 the annual mean
      entanglement rates varied from 3.6% to 5%. The maximum recapture period for
      entangled seals compared to paired control seals was significantly less (p=0.045)
      suggesting an increased mortality rate for affected seals. Of the 58 entangled
      cases in the catalogue, 64% had injuries that were deemed serious. Of the 15
      cases where the entangling debris was visible, 14 were entangled in fisheries
      materials. The entanglement reported at this site could indicate a high rate of
      mortality and should be monitored carefully. On a more immediate level,
      entanglement represents a welfare issue for the affected animals.

PMID- 23117202
TI  - Using EUNIS habitat classification for benthic mapping in European seas: present
      concerns and future needs.
AB  - The EUNIS (European Union Nature Information System) habitat classification
      system aims to provide a common European reference set of habitat types within a
      hierarchical classification, and to cover all terrestrial, freshwater and marine
      habitats of Europe. The classification facilitates reporting of habitat data in a
      comparable manner, for use in nature conservation (e.g. inventories, monitoring
      and assessments), habitat mapping and environmental management. For the marine
      environment the importance of a univocal habitat classification system is
      confirmed by the fact that many European initiatives, aimed at marine mapping,
      assessment and reporting, are increasingly using EUNIS habitat categories and
      respective codes. For this reason substantial efforts have been made to include
      information on marine benthic habitats from different regions, aiming to provide
      a comprehensive geographical coverage of European seas. However, there still
      remain many concerns on its applicability as only a small fraction of Europe's
      seas are fully mapped and increasing knowledge and application raise further
      issues to be resolved. This paper presents an overview of the main discussion and
      conclusions of a workshop, organised by the MeshAtlantic project, focusing upon
      the experience in using the EUNIS habitats classification across different
      countries and seas, together with case studies. The aims of the meeting were to:
      (i) bring together scientists with experience in the use of the EUNIS marine
      classification and representatives from the European Environment Agency (EEA);
      (ii) agree on enhancements to EUNIS that ensure an improved representation of the
      European marine habitats; and (iii) establish practices that make marine habitat
      maps produced by scientists more consistent with the needs of managers and
      decision-makers. During the workshop challenges for the future development of
      EUNIS were identified, which have been classified into five categories: (1)
      structure and hierarchy; (2) biology; (3) terminology; (4) mapping; and (5)
      future development. The workshop ended with a declaration from the attendees,
      with recommendations to the EEA and European Topic Centre on Biological
      Diversity, to take into account the outputs of the workshop, which identify
      weaknesses in the current classification and include proposals for its
      modification, and to devise a process to further develop the marine component of
      the EUNIS habitat classification.

PMID- 23117203
TI  - An evaluation of the toxicity and bioaccumulation of thallium in the coastal
      marine environment using the macroalga, Ulva lactuca.
AB  - Thallium(I) has been added to cultures of the marine macroalga, Ulva lactuca, for
      a period of 48 h and the accumulation of the metal and its effects on the
      photochemical efficiency of photosystem II (PS II) measured. Thallium elicited a
      measurable toxic response above concentrations of 10 MUg L-1 in both coastal
      seawater (salinity 33) and estuarine water (salinity 20). The accumulation of Tl
      was defined by a linear relationship with aqueous Tl and accumulation factors of
      about 900 mL g-1 in both media. Thallium accumulated by U. lactuca that was
      resistant to an EDTA extraction and, by operational definition, internalised,
      exceeded 90% in both cases. Accumulation and toxicity of Tl in the presence of a
      ~105-fold excess of its biogeochemical analogue, potassium, suggests that Tl has
      a high intrinsic phytotoxicity and that its mode of action involves permeation of
      the cell membrane as Tl+ through NaCl-KCl co-transporter sites rather than (or in
      addition to) transport through K+ ion channels.

PMID- 23117205
TI  - Differential impact of supported housing on selected subgroups of homeless
      veterans with substance abuse histories.
AB  - OBJECTIVE: Studies have demonstrated that supported housing is an effective
      intervention for individuals who are homeless and have a mental illness or
      substance use disorder. This study examined data from an experimental trial of
      the U.S. Department of Housing and Urban Development-Veterans Affairs Supported
      Housing (HUD-VASH) program to identify differences in the program's impact on
      subgroups defined by sociodemographic or clinical characteristics. METHODS: Data
      were analyzed from 259 male homeless veterans with substance abuse problems who
      were randomly assigned to HUD-VASH (intensive case management [ICM] plus rent
      subsidy vouchers), ICM only, or treatment as usual between June 1992 and December
      1995. Four subgroups were defined: African American versus Caucasian, younger
      versus older than 42.3 years, co-occurring diagnoses of mental illness versus
      diagnosis of a substance use disorder only, and active versus less active
      substance use upon program entry. Mixed models were used to identify significant
      interactions between HUD-VASH assignment and each subgroup. RESULTS: Compared
      with ICM alone, HUD-VASH was associated with more positive housing outcomes for
      Caucasians, veterans with co-occurring mental disorders, and veterans who were
      active substance users. HUD-VASH was associated with more positive socioclinical
      outcomes for African Americans. No differences were observed in housing or
      socioclinical outcomes as a function of age. CONCLUSIONS: Among homeless veterans
      with a substance use disorder, Caucasians and those with active substance use
      showed greater housing benefits than other veterans from HUD-VASH than from ICM
      alone. African Americans showed greater socioclinical benefit than Caucasians
      from HUD-VASH versus ICM. Interaction analysis deserves further study.

PMID- 23117206
TI  - Severe osteoporosis and mutation in NOTCH2 gene in a woman with Hajdu-Cheney
      syndrome.
AB  - Hajdu-Cheney syndrome (HCS) is a rare genetic disorder characterised by acro
      osteolysis, skull deformation and generalised osteoporosis. Recently, truncating
      mutations in the last exon of NOTCH2, a protein-coding gene, were found to be
      responsible. We present the case of a young woman with HCS in whom clinical and
      radiologic diagnosis was confirmed with DNA tests.

PMID- 23117207
TI  - The S349T mutation of SQSTM1 links Keap1/Nrf2 signalling to Paget's disease of
      bone.
AB  - Mutations affecting the Sequestosome 1 (SQSTM1) gene commonly occur in patients
      with the skeletal disorder Paget's disease of bone (PDB), a condition
      characterised by defective osteoclast differentiation and function. Whilst most
      mutations cluster within the ubiquitin-associated (UBA) domain of the SQSTM1
      protein, and are associated with dysregulated NFkappaB signalling, several non
      UBA domain mutations have also been identified. Keap1 is a SQSTM1-interacting
      protein that regulates the levels and activity of the Nrf2 transcription factor.
      This in turn controls the expression of numerous cytoprotective genes that
      contribute to the cell's capacity to defend itself against chemical and oxidative
      stress, through binding to the antioxidant response element (ARE). The PDB
      associated S349T mutation maps to the Keap1-interacting region (KIR) of SQSTM1,
      however the effects of PDB mutant SQSTM1 on Keap1 function have not been
      investigated. Here we show that unlike other SQSTM1 mutations, the S349T mutation
      results in neither impaired ubiquitin-binding function in pull-down assays, nor
      dysregulated NFkappaB signalling in luciferase reporter assays. Keap1 is
      expressed in differentiating osteoclast-like cells and the S349T mutation
      selectively impairs the SQSTM1-Keap1 interaction in co-immunoprecipitations,
      which molecular modelling indicates results from effects on critical hydrogen
      bonds required to stabilise the KIR-Keap1 complex. Further, S349T mutant SQSTM1,
      but not other PDB-associated mutants, showed reduced ability to activate Nrf2
      signalling as assessed by ARE-luciferase reporter assays. Thus, SQSTM1-mediated
      dysregulation of the Keap1-Nrf2 axis, which could potentially lead to aberrant
      production of oxidative response genes, may contribute to disease aetiology in a
      subset of PDB patients.

PMID- 23117209
TI  - High consumption of smokeless tobacco ("snus") predicts increased risk of type 2
      diabetes in a 10-year prospective study of middle-aged Swedish men.
AB  - AIMS: Cigarette smoking increases the risk of type 2 diabetes (T2D). In Sweden
      and the US, people shift from smoking cigarettes to smokeless tobacco, i.e. oral
      moist snuff, "snus", to attain harm-reduction. There are limited and conflicting
      data as to whether snus increases the risk of T2D. The present study investigated
      if snus use predicts the risk of T2D incidence. METHODS: This is a prospective
      population-based study where middle-aged Swedish men (n=2,383), without
      previously diagnosed T2D, were investigated with oral glucose tolerance test
      (OGTT) at baseline in 1992-94 and at follow-up 10 years later. Odds ratios (ORs)
      for newly diagnosed T2D at follow-up were assessed among those using snus, or
      cigarettes, at both baseline and follow-up, adjusted for major confounders.
      RESULTS: The OR for T2D was not significantly increased in the whole group of
      snus users. However, the risk of diabetes increased with increasing weekly snus
      consumption; ORs (CIs) for >four boxes of snus/week were 2.1 (CI 0.9-4.9), and
      for >five boxes/week 3.3 (CI 1.4-8.1). For comparison, men smoking at baseline
      and still smoking at follow-up had an increased risk of diabetes compared with
      never smokers, OR 1.5 (CI 0.8-3.0), most evident for those smoking >15 cigarettes
      per day, OR 2.4 (CI 1.0-5.8). Tobacco use was associated with estimations of low
      insulin response (OGTT), but not low insulin sensitivity (HOMA). CONCLUSIONS:
      High consumption of snus, like smoking, predicts risk of developing T2D. This
      should be considered when seeking harm-reduction by changing from use of
      cigarettes to snus. T2D risk from tobacco use may be mediated by effects on beta
      cell function.

PMID- 23117208
TI  - Impact of Charcot neuroarthropathy on metatarsal bone mineral density and
      geometric strength indices.
AB  - Charcot neuroarthropathy (CN), an inflammatory condition characterized by rapid
      and progressive destruction of pedal bones and joints, often leads to deformity
      and ulceration in individuals with diabetes mellitus (DM) and peripheral
      neuropathy (PN). Repetitive, unperceived joint trauma may trigger initial CN
      damage, causing a proinflammatory cascade that can result in osteolysis and
      contribute to subsequent neuropathic fracture. We aimed to characterize
      osteolytic changes related to development and progression of CN by measuring bone
      mineral density (BMD) and geometric strength indices using volumetric
      quantitative computed tomography. Twenty individuals with DM+PN were compared to
      twenty age-, sex-, and race-matched individuals with DM+PN and acute CN. We
      hypothesized that individuals with acute CN would have decreased BMD and
      decreased total area, cortical area, minimum section modulus, and cortical
      thickness in the diaphysis of the second and fifth metatarsals. Results showed
      BMD was lower in both involved and uninvolved feet of CN participants compared to
      DM+PN participants, with greater reductions in involved CN feet compared to
      uninvolved CN feet. There was a non-significant increase in total area and
      cortical area in the CN metatarsals, which helps explain the finding of similar
      minimum section modulus in DM+PN and CN subjects despite the CN group's
      significantly lower BMD. Larger cortical area and section modulus are typically
      considered signs of greater bone strength due to higher resistance to compressive
      and bending loads, respectively. In CN metatarsals, however, these findings may
      reflect periosteal woven bone apposition, i.e., a hypertrophic response to injury
      rather than increased fracture resistance. Future research using these techniques
      will aid further understanding of the inflammation-mediated bony changes
      associated with development and progression of CN and other diseases.

PMID- 23117210
TI  - Adaptation and validation of the Cambridge pulmonary hypertension outcome review
      for Sweden.
AB  - BACKGROUND: The Cambridge pulmonary hypertension outcome review (CAMPHOR) is the
      first pulmonary hypertension-specific instrument for the assessment of the
      patient's perceived symptoms, activity limitations and quality of life (QoL).
      PURPOSE: To produce and validate a Swedish language version of the CAMPHOR.
      METHODS: Bilingual (n = 5) and lay panels (n = 5) were conducted to translate the
      CAMPHOR into Swedish. This new questionnaire was then field-tested with 14
      patients and finally, it underwent psychometric evaluation by means of a postal
      validation study involving 38 patients with pulmonary hypertension (PH). RESULTS:
      Few problems were experienced in translating the CAMPHOR into Swedish. The field
      test participants found the scales relevant, comprehensible and easy to complete.
      Psychometric analyses showed that the Swedish adaptation was successful. The
      Swedish CAMPHOR scales had good internal consistency. Cronbach's alpha
      coefficients were 0.92 for the symptoms scale, 0.92 for activity limitations and
      0.95 for the quality of life. Predicted correlations with the Nottingham Health
      Profile provided evidence of the construct validity of the scales. The Swedish
      scales also indicated known groups validity. CONCLUSIONS: The Swedish version of
      the CAMPHOR is a reliable and valid measure of the impact of pulmonary
      hypertension on the lives of affected patients. It is recommended for use in
      clinical studies and routine practice in pulmonary hypertension patients.

PMID- 23117211
TI  - DodaLab: an urban health and demographic surveillance site, the first three years
      in Hanoi, Vietnam.
AB  - RATIONALE: Health and demographic surveillance sites (HDSSs) are important
      sources for health planning and policy in many low and middle income countries.
      Almost all HDSSs are in rural settings. The article aims to present the
      experiences and some concrete results for the first three years of operation of
      an urban HDSS in Hanoi, Vietnam, and discuss advantages and disadvantages of
      conducting health studies in HDSSs. DESIGN, POPULATION AND SAMPLE SIZE: The
      DodaLab urban HDSS was established in 2007 in three communes at different
      economic levels in Dong Da district, Hanoi, Vietnam. Demographic, social and
      economic information about 10,000 households and their 37,000 persons was
      obtained through household interviews. Quarterly follow-up was initiated to
      provide information about vital events, birth, death and migration. A new
      household survey was undertaken in 2009. The existing rural HDSS FilaBavi,
      started in 1999, with 12,000 households and 52,000 persons, was used as the
      blueprint. CONCLUSIONS: It was possible to establish and run an urban HDSS with
      experiences from the rural site. The urban and rural contexts are different and
      demographically, economically and socially complex, but the use of HDSSs can
      facilitate research beyond very simplified models for comparisons. General
      statements about external validity of results from the HDSS cannot be made. This
      issue has to be considered specifically in every situation as an integral part of
      the research so that the results can be made useful outside the researched HDSS
      and in performing relevant comparisons.

PMID- 23117213
TI  - Network formation through active migration of human vascular endothelial cells in
      a multilayered skeletal myoblast sheet.
AB  - Autologous transplantation of myoblast sheet has attracted attention as a new
      technique for curing myocardial infarction. Myoblast sheet has the ability to
      secret cytokines that improve heart function via the facilitation of angiogenesis
      on affected part. To mimic the in vivo angiogenesis in the myoblast sheet after
      transplantation, a five-layered cell sheet of human skeletal muscle myoblasts
      (HSMMs) was overlaid on human umbilical vein endothelial cells (HUVECs) which
      enables evaluation of dynamic HUVEC behavior. HUVECs existing initially at the
      bottom of the sheet changed to be a stretched shape and migrated upward compared
      with the surrounding HSMMs in the sheet. Prolonged incubation resulted in network
      formation of HUVECs in the middle of the sheet, although non-networked HUVECs
      continued to migrate to the top of the sheet, which meant the spatial habitation
      of HUVECs in the cell sheet. Image processing was performed to determine the
      variation in the extent of network formation at different HUVEC densities. It was
      found that the extent of formed network depended on the frequency of encounters
      among HUVECs in the middle of the sheet. The present system, which can evaluate
      network formation, is considered to be a promising in vitro angiogenesis model.

PMID- 23117212
TI  - A comparison of blood factor XII autoactivation in buffer, protein cocktail,
      serum, and plasma solutions.
AB  - Activation of blood plasma coagulation in vitro by contact with material surfaces
      is demonstrably dependent on plasma-volume-to-activator-surface-area ratio. The
      only plausible explanation consistent with current understanding of coagulation
      cascade biochemistry is that procoagulant stimulus arising from the activation
      complex of the intrinsic pathway is dependent on activator surface area. And yet,
      it is herein shown that activation of the blood zymogen factor XII (Hageman
      factor, FXII) dissolved in buffer, protein cocktail, heat-denatured serum, and
      FXI deficient plasma does not exhibit activator surface-area dependence. Instead,
      a highly-variable burst of procoagulant-enzyme yield is measured that exhibits no
      measurable kinetics, sensitivity to mixing, or solution-temperature dependence.
      Thus, FXII activation in both buffer and protein-containing solutions does not
      exhibit characteristics of a biochemical reaction but rather appears to be a
      "mechanochemical" reaction induced by FXII molecule interactions with hydrophilic
      activator particles that do not formally adsorb blood proteins from solution.
      Results of this study strongly suggest that activator surface-area dependence
      observed in contact activation of plasma coagulation does not solely arise at the
      FXII activation step of the intrinsic pathway.

PMID- 23117215
TI  - Incorporation of stromal cell-derived factor-1alpha in PCL/gelatin electrospun
      membranes for guided bone regeneration.
AB  - The goal of this work was to evaluate the effect of membrane functionalization
      with a chemotactic factor on cell recruitment and bone formation in order to
      develop a bioactive membrane for guided bone regeneration (GBR) applications. To
      this end, GBR membranes were prepared by electrospinning using poly(epsilon
      caprolactone) (PCL) blended with type B-gelatin, and functionalized with stromal
      cell derived factor-1alpha (SDF-1alpha) via physical adsorption. Firstly, the
      obtained membranes were evaluated in vitro for SDF-1alpha release and chemotactic
      effect on bone marrow stromal cells (BMSCs). Subsequently, in vivo BMSCs
      recruitment and bone regeneration in response to SDF-1alpha loaded PCL/gelatin
      electrospun membranes were assessed in rat cranial defects. The results showed
      that PCL/gelatin electrospun membranes provided a diffusion-controlled SDF-1alpha
      release profile. Furthermore, the membranes loaded with different amounts of SDF
      1alpha (50-400 ng) significantly induced stimulated chemotactic migration of
      BMSCs in vitro without dose-dependent effects. Eight weeks after implantation in
      rat cranial defects, SDF-1alpha loaded membranes yielded a 6-fold increase in the
      amount of bone formation compared to the bare membranes, albeit that contribution
      of in vivo BMSCs recruitment to the bone regeneration could not be ascertained.
      In conclusion, the results of current study indicate the potential for using SDF
      1alpha loaded PCL/gelatin electrospun membrane as a bioactive membrane, which is
      beneficial for optimizing clinical application of GBR strategies.

PMID- 23117214
TI  - Activation of an immune-regulatory macrophage response and inhibition of lung
      inflammation in a mouse model of COPD using heat-shock protein alpha B-crystallin
      loaded PLGA microparticles.
AB  - As an extracellular protein, the small heat-shock protein alpha B-crystallin
      (HSPB5) has anti-inflammatory effects in several mouse models of inflammation.
      Here, we show that these effects are associated with the ability of HSPB5 to
      activate an immune-regulatory response in macrophages via endosomal/phagosomal
      CD14 and Toll-like receptors 1 and 2. Humans, however, possess natural antibodies
      against HSPB5 that block receptor binding. To protect it from these antibodies,
      we encapsulated HSPB5 in porous PLGA microparticles. We document here size,
      morphology, protein loading and release characteristics of such microparticles.
      Apart from effectively protecting HSPB5 from neutralization, PLGA microparticles
      also strongly promoted macrophage targeting of HSPB via phagocytosis. As a
      result, HSPB5 in porous PLGA microparticles was more than 100-fold more effective
      in activating macrophages than free soluble protein. Yet, the immune-regulatory
      nature of the macrophage response, as documented here by microarray transcript
      profiling, remained the same. In mice developing cigarette smoke-induced COPD,
      HSPB5-loaded PLGA microparticles were selectively taken up by alveolar
      macrophages upon intratracheal administration, and significantly suppressed lung
      infiltration by lymphocytes and neutrophils. In contrast, 30-fold higher doses of
      free soluble HSPB5 remained ineffective. Our data indicate that porous HSPB5-PLGA
      microparticles hold considerable promise as an anti-inflammatory biomaterial for
      humans.

PMID- 23117216
TI  - Hydrothermal synthesis of NaLuF4:153Sm,Yb,Tm nanoparticles and their application
      in dual-modality upconversion luminescence and SPECT bioimaging.
AB  - Upconversion luminescence (UCL) properties and radioactivity have been integrated
      into NaLuF(4):(153)Sm,Yb,Tm nanoparticles by a facile one-step hydrothermal
      method, making these nanoparticles potential candidates for UCL and single-photon
      emission computed tomography (SPECT) dual-modal bioimaging in vivo. The
      introduction of small amount of radioactive (153)Sm(3+) can hardly vary the
      upconversion luminescence properties of the nanoparticles. The as-designed
      nanoparticles showed very low cytotoxicity, no obvious tissue damage in 7 days,
      and excellent in vitro and in vivo performances in dual-modal bioimaging. By
      means of a combination of UCL and SPECT imaging in vivo, the distribution of the
      nanoparticles in living animals has been studied, and the results indicated that
      these particles were mainly accumulated in the liver and spleen. Therefore, the
      concept of (153)Sm(3+)/Yb(3+)/Tm(3+) co-doped NaLuF(4) nanoparticles for UCL and
      SPECT dual-modality imaging in vivo of whole-body animals may serve as a platform
      for next-generation probes for ultra-sensitive molecular imaging from the
      cellular scale to whole-body evaluation. It also introduces an easy methodology
      to quantify in vivo biodistribution of nanomaterials which still needs further
      understanding as a community.

PMID- 23117217
TI  - A specific peptide ligand-modified lipid nanoparticle carrier for the inhibition
      of tumor metastasis growth.
AB  - Tumor metastasis accounts for 90% of cancer-associated deaths and is almost
      inaccessible by chemotherapy, surgical operation or radiotherapy. Here, a tumor
      metastasis-specific nanocarrier system has been constructed by modification of
      stealth lipid nanoparticles with a specific peptide ligand. Highly metastatic
      breast cancer MDA-MB-231 that stably expressed luciferase (MDA-MB-231/Luc) was
      used as tumor cell model. The nanocarrier was very specific for highly metastatic
      cancer cells in vitro and could specifically target to cancer metastases foci
      following systemic administration in vivo by both fluorescence imaging and
      bioluminescence imaging compared to a passive-targeted system. It greatly
      facilitated the efficacy of doxorubicin loaded in inhibiting tumor metastasis
      growth and prolonging the survival time of mice. Importantly, this system was
      also found to prevent the initiation and progression of tumor metastasis. The
      tumor metastasis-targeted nanocarriers hold great potential in the treatment of
      cancer metastasis foci and even for the prevention of tumor metastasis. This
      study may also provide new strategy in the development of nanomedicine for
      diagnosis and therapy of tumor metastasis.

PMID- 23117218
TI  - Adjuvant occupational therapy improves long-term depression recovery and return
      to-work in good health in sick-listed employees with major depression: results of
      a randomised controlled trial.
AB  - OBJECTIVES: To evaluate whether adjuvant occupational therapy (OT) can improve
      the effectiveness of treatment-as-usual (TAU) in sick-listed employees with major
      depression. METHODS: In total, 117 employees sick-listed for a median duration of
      4.8 months (IQR=2.6 to 10.1 months) because of major depression were randomised
      to TAU (n=39) or adjuvant OT (TAU+OT; n=78). OT (18 sessions) focussed on a fast
      return to work (RTW) and improving work-related coping and self-efficacy. The
      primary outcome was work participation (hours of absenteeism+duration until
      partial/full RTW). Secondary outcomes were depression, at-work functioning, and
      health-related functioning. Intermediate outcomes were work-related, coping and
      self-efficacy. Blinded assessments occurred at baseline and 6, 12 and 18 months
      follow-up. RESULTS: The groups did not significantly differ in their overall work
      participation (adjusted group difference=-1.9, 95% CI -19.9 to +16.2). However,
      those in TAU+OT did show greater improvement in depression symptoms (-2.8, -5.5
      to -0.2), an increased probability of long-term symptom remission (+18%, +7% to
      +30%), and increased probability of long-term RTW in good health (GH) (+24%, 12%
      to 36%). There were no significant group differences in the remaining
      secondary/intermediate outcomes. CONCLUSIONS: In a highly impaired population, we
      could not demonstrate significant benefit of adjuvant OT for improving overall
      work participation. However, adjuvant OT did increase long-term depression
      recovery and long-term RTW in GH (ie, full RTW while being remitted, and with
      better work and role functioning). TRIAL REGISTRATION DUTCH TRIAL REGISTER:
      NTR2057.

PMID- 23117219
TI  - Lymphoma risk and occupational exposure to pesticides: results of the Epilymph
      study.
AB  - OBJECTIVES: We investigated the role of occupational exposure to specific groups
      of agrochemicals in the aetiology of lymphoma overall, B cell lymphoma and its
      most prevalent subtypes. METHODS: In 1998-2003, 2348 incident lymphoma cases and
      2462 controls were recruited to the EPILYMPH case-control study in six European
      countries. A detailed occupational history was collected in cases and controls.
      Job modules were applied for farm work including specific questions on type of
      crop, farm size, pests being treated, type and schedule of pesticide use. In each
      study centre, industrial hygienists and occupational experts assessed exposure to
      specific groups of pesticides and individual compounds with the aid of
      agronomists. We calculated the OR and its 95% CI associated with lymphoma and the
      most prevalent lymphoma subtypes with unconditional logistic regression,
      adjusting for age, gender, education and centre. RESULTS: Risk of lymphoma
      overall, and B cell lymphoma was not elevated, and risk of chronic lymphocytic
      leukaemia (CLL) was elevated amongst those ever exposed to inorganic (OR=1.6, 95%
      CI 1.0 to 2.5) and organic pesticides (OR=1.5, 95% CI 1.0 to 2.1). CLL risk was
      highest amongst those ever exposed to organophosphates (OR=2.7, 95% CI 1.2 to
      6.0). Restricting the analysis to subjects most likely exposed, no association
      was observed between pesticide use and risk of B cell lymphoma. CONCLUSIONS: Our
      results provide limited support to the hypothesis of an increase in risk of
      specific lymphoma subtypes associated with exposure to pesticides.

PMID- 23117220
TI  - Look into my eyes and I will see you: unconscious processing of human gaze.
AB  - This study examines whether human gaze lacking the confounding factor of eye
      whites can be processed unconsciously and explores the critical aspects for such
      process. Utilizing the continuous flash suppression paradigm, a schematic face-
      with direct or averted gaze, and with neutral, fearful or happy expressions--was
      presented to one eye while dynamic masks rendered it invisible to the other eye.
      Schematic faces were used to avoid unwanted influence from salient eye whites.
      Participants' detection time of anything other than the masks was used as an
      index of unconscious processing time. Faster detection was found for faces with
      direct gaze than those with averted gaze. However, there was no difference
      between detection times for different facial expressions (Experiment 1) and
      upright-face, inverted-face, and eyes-only conditions (Experiment 2). These
      results confirm that, with schematic faces, gaze can be processed unconsciously
      regardless of facial expression, and eyes alone are sufficient for such process.

PMID- 23117221
TI  - The Hatoyama Cohort Study: design and profile of participants at baseline.
AB  - BACKGROUND: Investigation of frailty among elderly adults and development of
      prevention strategies to address this are critical in delaying progression of
      functional decline and thus extending healthy life expectancy. However, there has
      been no Japanese epidemiologic cohort study of frailty. The Hatoyama Cohort Study
      was launched in 2010 to identify factors that predict functional decline and to
      establish strategies to prevent frailty among community-dwelling elderly
      Japanese. This report describes the study design and the profile of the
      participants at baseline. METHODS: The Hatoyama Cohort Study is a prospective
      study of community-dwelling individuals aged 65 years or older living in the town
      of Hatoyama in Saitama Prefecture, Japan. Comprehensive information, including
      socioeconomic status, physiological indicators, physical, psychological, and
      cognitive function, social capital, neighborhood environment, and frailty, was
      collected in a baseline survey using face-to-face interviews in September 2010.
      Survival time, long-term care insurance certification, and medical and long-term
      care costs after the baseline survey will be followed. In addition, a follow-up
      survey will be conducted in the same manner as the baseline survey every 2 years.
      RESULTS: A total of 742 people participated in the baseline survey (mean age:
      71.9 +/- 5.2 years, men: 57.7%, living alone: 7.7%). Almost all participants were
      independent in their daily lives, and approximately 10% were categorized as frail
      on the kaigo-yobo (care prevention) checklist. CONCLUSIONS: The Hatoyama Cohort
      Study is expected to contribute to the development of strategies that prevent
      frailty in later life and extend healthy life expectancy in Japan's rapidly aging
      society.

PMID- 23117222
TI  - Positive and negative effects of finance-based social capital on incident
      functional disability and mortality: an 8-year prospective study of elderly
      Japanese.
AB  - BACKGROUND: Rotating savings and credit associations (ROSCAs) involve group
      financial self-help activities. These voluntary financial cooperative
      associations-mujin in Japanese-are found in some rural areas of Japan. Cross
      sectional evidence suggests that active participation in mujin correlates with
      rich social capital and better functional capacities among older adults. However,
      the effect of mujin on subsequent health outcomes is unknown. METHODS: In 2003,
      we conducted a baseline interview survey of 583 functionally independent adults
      randomly selected from Yamanashi Prefecture residents aged 65 years or older.
      They were followed up until 2011. We used proportional hazards models, and factor
      analysis of 8 mujin-related questions identified 2 components: the "intensity and
      attitude" and "financing" aspects of mujin. RESULTS: The hazard ratios (HRs) for
      incident functional disability-identified by using the public long-term care
      insurance database-per 1-SD increase in factor scores were 0.82 (95% CI: 0.68
      0.99) for the intensity and attitude score and 1.21 (1.07-1.38) for financing
      score. Adjustments for age, sex, marital status, household composition, physical
      health, education, income, and other factor scores only slightly attenuated these
      HRs. The results for mortality models were very similar to those for incident
      functional disability. CONCLUSIONS: ROSCA-type activities in Japan could have
      beneficial effects on the health of older adults if used primarily for the
      purpose of friendship. Mujin for aggressively financial purposes might be
      somewhat harmful, as such activities might reflect the "dark side" of social
      capital, ie, overly demanding expectations of group conformity.

PMID- 23117223
TI  - Revised system to evaluate measurement of blood chemistry data from the Japanese
      National Health and Nutrition Survey and Prefectural Health and Nutrition
      Surveys.
AB  - BACKGROUND: We developed a monitoring system that uses total errors (TEs) to
      evaluate measurement of blood chemistry data from the National Health and
      Nutrition Survey (NHNS) and Prefectural Health and Nutrition Surveys (PHNS).
      METHODS: Blood chemistry data from the NHNS and PHNS were analyzed by SRL, Inc.,
      a commercial laboratory in Tokyo, Japan. Using accuracy and precision from
      external and internal quality controls, TEs were calculated for 14 blood
      chemistry items during the period 1999-2010. The acceptable range was defined as
      less than the upper 80% confidence limit for the median, the unacceptable range
      as more than twice the cut-off value of the acceptable range, and the borderline
      range as the interval between the acceptable and unacceptable ranges. RESULTS:
      The TE upper limit for the acceptable and borderline ranges was 5.7% for total
      cholesterol (mg/dL), 9.9% for high-density lipoprotein cholesterol (mg/dL), 10.0%
      for low-density lipoprotein cholesterol (mg/dL), 10.4% for triglycerides (mg/dL),
      6.6% for total protein (g/dL), 7.6% for albumin (g/dL), 10.8% for creatinine
      (mg/dL), 6.5% for glucose (mg/dL), 9.7% for gamma-glutamyl transpeptidase (U/L),
      7.7% for uric acid (mg/dL), 8.7% for urea nitrogen (mg/dL), 9.2% for aspartate
      aminotransferase (U/L), 9.5% for alanine aminotransferase (U/L), and 6.5% for
      hemoglobin A1c (%). CONCLUSIONS: This monitoring system was established to assist
      health professionals in evaluating the continuity and comparability of NHNS and
      PHNS blood chemistry data among survey years and areas and to prevent biased or
      incorrect conclusions.

PMID- 23117225
TI  - Enhancing the mass sensitivity of graphene nanoresonators via nonlinear
      oscillations: the effective strain mechanism.
AB  - We perform classical molecular dynamics simulations to investigate the
      enhancement of the mass sensitivity and resonant frequency of graphene
      nanomechanical resonators that is achieved by driving them into the nonlinear
      oscillation regime. The mass sensitivity as measured by the resonant frequency
      shift is found to triple if the actuation energy is about 2.5 times the initial
      kinetic energy of the nanoresonator. The mechanism underlying the enhanced mass
      sensitivity is found to be the effective strain that is induced in the
      nanoresonator due to the nonlinear oscillations, where we obtain an analytic
      relationship between the induced effective strain and the actuation energy that
      is applied to the graphene nanoresonator. An important implication of this work
      is that there is no need for experimentalists to apply tensile strain to the
      resonators before actuation in order to enhance the mass sensitivity. Instead,
      enhanced mass sensitivity can be obtained by the far simpler technique of
      actuating nonlinear oscillations of an existing graphene nanoresonator.

PMID- 23117224
TI  - Riluzole and prognostic factors in amyotrophic lateral sclerosis long-term and
      short-term survival: a population-based study of 1149 cases in Taiwan.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a rare disease in Taiwan;
      thus, estimation of ALS mortality is difficult. We evaluated factors associated
      with ALS survival in Taiwan. METHODS: The study enrolled 1149 Taiwanese with a
      primary diagnosis of ALS during 1999-2008. Follow-up information was available
      for all patients; mean (SD) duration of follow-up was 2.91 (2.62) years. Medical
      interventions, including noninvasive positive pressure ventilation (NIPPV),
      tracheotomy, gastrostomy, and riluzole, were included in time-dependent survival
      analysis. RESULTS: Of the 1149 ALS patients, 438 (38.12%) died during follow-up.
      Mortality in the first year was 16%, which was 13 times (95% CI 11.1-15.2) the
      age- and sex-standardized rate of the general population in Taiwan. The average
      annual crude mortality rate was 13.1% (person-years). Factors significantly
      associated with increased mortality were male sex, advanced age, rural residence,
      lower economic status, no tracheotomy, and no riluzole treatment. Significant
      predictors of long-term versus average survival were younger age at diagnosis,
      being a dependent or receiving social welfare, and NIPPV support. Significant
      predictors of short-term versus average survival were older age, being employed,
      no tracheotomy, and no riluzole use. CONCLUSIONS: The results support the use of
      riluzole to improve ALS survival. Patients who received riluzole and underwent
      tracheotomy had the best survival.

PMID- 23117226
TI  - Analytical expressions for the steady-state concentrations of glucose, oxygen and
      gluconic acid in a composite membrane for closed-loop insulin delivery.
AB  - The mathematical model of Abdekhodaie and Wu (J Membr Sci 335:21-31, 2009) of
      glucose-responsive composite membranes for closed-loop insulin delivery is
      discussed. The glucose composite membrane contains nanoparticles of an anionic
      polymer, glucose oxidase and catalase embedded in a hydrophobic polymer. The
      model involves the system of nonlinear steady-state reaction-diffusion equations.
      Analytical expressions for the concentration of glucose, oxygen and gluconic acid
      are derived from these equations using the Adomian decomposition method. A
      comparison of the analytical approximation and numerical simulation is also
      presented. An agreement between analytical expressions and numerical results is
      observed.

PMID- 23117229
TI  - Lateralized suckling in domestic horses (Equus caballus).
AB  - Brain lateralization enables preferential processing of certain stimuli and more
      effective utilization of these stimuli in either the left or the right cerebral
      hemisphere. Horses show both motor and sensory lateralization patterns. Our aim
      was to determine whether a lateralized response could be detected in foals during
      the naturally side-biased behaviour, suckling. The foals' preferred suckling side
      could be the effect of either visual or motor lateralization. In the case of a
      visual lateralized response, foals are expected to suck more often from the
      mother's right side, so potential danger can be detected by the better adapted
      right hemisphere (i.e. left eye). Motor lateralization can be identified when a
      foal will suck predominantly from one side, either left or right. We found no
      population trend in the preferred suckling side, but we detected significant
      differences amongst individual foals. One-third (35.4 %) of 79 foals showed a
      strong, either right or left side preference which increased with age. The
      mothers did not influence the foals' suckling side preferences either by side
      biased rejection or termination of suckling. According to our findings, a general
      pattern of sucking with the left eye open for better danger detection and
      recognition is unlikely in foals up to 7 months old. Foals of this age are
      probably young or fully focused on suckling and rely on their mothers' vigilance.
      Individual side preferences amongst foals are suggested to be based on motor
      lateralization.

PMID- 23117227
TI  - Catabolism of amino acids in livers from cafeteria-fed rats.
AB  - Most studies using a hypercaloric diet to induce obesity have focused on the
      metabolism of fat and carbohydrates. Less concern has been given to the
      metabolism of amino acids, despite evidence of modifications in nitrogen
      metabolism during obesity. The aim of this study was to evaluate amino acid
      metabolism in livers from cafeteria diet-induced obese rats. Blood parameters
      were analysed, and histological sections of livers were stained with Sudan III.
      The enzymatic activities of some enzymes were determined in liver homogenates.
      Gluconeogenesis, ureagenesis, and oxygen consumption were evaluated in rat livers
      perfused with glutamine, alanine, or ammonium chloride. Compared to control rats,
      cafeteria-fed rats demonstrated higher levels of triacylglycerol and glucose in
      the blood and greater accumulation of fat in livers. Gluconeogenesis and urea
      production in livers perfused with glutamine and alanine at higher concentrations
      showed a substantial reduction in cafeteria-fed rats. However, no significant
      difference was observed among groups perfused with ammonium chloride. The
      activities of the enzymes alanine aminotransferase, glutaminase, and aspartate
      aminotransferase in the livers were reduced in cafeteria-fed rats. Taken
      together, these data are consistent with the hypothesis that livers from
      cafeteria diet-induced obese rats exhibit a limitation in their maximal capacity
      to metabolise glutamine and alanine to glucose, ammonia, and urea, not because of
      an impairment in gluconeogenesis and/or ureagenesis, but rather due to a
      depression in the activities of enzymes that catalyse the initial steps of amino
      acid metabolism.

PMID- 23117228
TI  - Catechin induced modulation in the activities of thyroid hormone synthesizing
      enzymes leading to hypothyroidism.
AB  - Catechins, the flavonoids found in abundance in green tea, have many beneficial
      health effects such as antioxidative, anticarcinogenic, anti-inflammatory,
      antiallergic, and hypotensive properties. However, flavonoids have
      antithyroid/goitrogenic effect, although less information is available about the
      effect of pure catechin on thyroid physiology. The present investigation has been
      undertaken to explore the effect of catechin administration on thyroid physiology
      in rat model. For the in vivo experiment catechin was injected intraperitoneally
      (i.p.) at doses of 10, 20 and 30 mg/kg body to male albino rats for 15 and 30
      days, respectively, and thyroid activities were evaluated with respect to
      determination of serum levels of thyroid hormones, thyroid peroxidase, 5'
      deiodinase I (5'-DI), and Na(+), K(+)-ATPase activities that are involved in the
      synthesis of thyroid hormone. Catechin decreased the activities of thyroid
      peroxidase and thyroidal 5'-deiodinase I, while Na(+), K(+)-ATPase activity
      significantly increased in dose-dependent manner; substantial decrease in serum
      T3 and T4 levels coupled with significant elevation of serum TSH were also noted.
      Histological examinations of the thyroid gland revealed marked hypertrophy and/or
      hyperplasia of the thyroid follicles with depleted colloid content. In in vitro
      study, short-term exposure of rat thyroid tissue to catechin at the
      concentrations of 0.10, 0.20, and 0.30 mg/ml leads to decrease in the activities
      of thyroid peroxidase and 5'-deiodinase I, while the activity of thyroidal Na(+),
      K(+)-ATPase remains unaltered even at high concentration of catechin treatment.
      The present study reinforces the concept that catechin, tea flavonoids possess
      potent antithyroid activity as evidenced from in vivo and in vitro studies.

PMID- 23117230
TI  - Cyclopeptoids: a novel class of phase-transfer catalysts.
AB  - The synthesis, complexation properties and catalytic activities under phase
      transfer (PT) conditions of differently substituted cyclohexapeptoids are
      reported. Association constants, for small cationic alkali, and catalytic
      performances, in a model nucleophilic substitution, are comparable to those of
      representative crown ethers. Noteworthy, the N-[2-(2-methoxyethoxy)ethyl] side
      chain derivative presents a catalytic efficiency comparable to that of crypt-222,
      and higher than some commonly used quaternary ammonium salts and crown ethers.
      Moreover its association constant for Na(+) complexation proved to be higher when
      compared with dicyclohexyl-18-crown-6. The synthesized cyclohexapeptoids
      represent the first example of these peptidomimetics in PT catalysis,
      anticipating interesting applications in biphasic PT methodology.

PMID- 23117231
TI  - Videothoracoscopic repair of diaphragm and pleurectomy/abrasion in patients with
      catamenial pneumothorax: a 9-year experience.
AB  - BACKGROUND: Catamenial pneumothorax (CP) is a cause of recurrent pneumothorax in
      women of child-bearing age. Surgical treatment has been associated with high
      recurrence rates. We report our experience with a totally videothoracoscopic
      approach involving diaphragmatic repair, pleurectomy/abrasion, and hormonal
      treatment in patients with proven CP. METHODS: This was a retrospective study of
      all patients with proven CP operated on by a single surgeon using a
      videothoracoscopic approach, diaphragmatic repair, and pleurectomy/pleural
      abrasion. A polytetrafluoroethylene mesh was used to cover the diaphragm in
      patients with pores or fenestrations. All patients received hormone therapy for 6
      to 12 months postoperatively and were followed up to assess complications and
      recurrence. RESULTS: Twelve patients were identified as having CP. All patients
      except one had suffered right sided pneumothorax only. One patient also had a
      history of left-sided pneumothorax managed conservatively at another institution.
      All cases except one underwent a primary operation. One patient had previously
      had videothoracoscopic pleurodesis without diaphragm repair at another center. In
      all cases, findings typical of CP were identified within the pleural cavity,
      mainly on the diaphragm. In three patients, no diaphragmatic pores or
      fenestrations were noted. There were no postoperative complications and no
      mortality. Median follow-up was 45.8 28.6 months. One patient suffered a single
      episode of recurrence before starting hormonal therapy, treated conservatively.
      CONCLUSIONS: A totally videothoracoscopic approach to CP including diaphragmatic
      cover with a mesh and pleurectomy/pleural abrasion is feasible, safe, and highly
      effective. Routine hormonal treatment (gonadotropin-releasing hormone analog) may
      also help reduce recurrences.

PMID- 23117232
TI  - Expression of GALNT2 in human extravillous trophoblasts and its suppressive role
      in trophoblast invasion.
AB  - Extravillus trophoblast (EVT) invasion plays a critical role in placental
      development. Integrins bind to extracellular matrix (ECM) proteins to mediate EVT
      cell adhesion, migration, and invasion. Changes in O-glycans on beta1-integrin
      have been found to regulate cancer cell behavior. We hypothesize that O
      glycosyltransferases can regulate EVT invasion through modulating the
      glycosylation and function of beta1-integrin. Here, we found that the GALNT1 and
      GALNT2 mRNA were highly expressed in HTR8/SVneo and first trimester EVT cells.
      Immunohistochemstry and immunofluorescence staining showed that GALNT2 was
      expressed in subpopulations of EVT cells in deciduas, but not in
      syncytiotrophoblasts and cytotrophoblasts of placental villi. The percentage of
      GALNT2-positive EVT cells increased with gestational ages. Overexpression of
      GALNT2 in HTR8/SVneo cells significantly enhanced cell-collagen IV adhesion, but
      suppressed cell migration and invasion. Notably, we found that GALNT2 increased
      the expression of Tn antigen (GalNAc-Ser/Thr) on beta1-integrin as revealed by
      Vicia Villosa agglutinin (VVA) binding. Furthermore, GALNT2 suppressed the
      phosphorylation of focal adhesion kinase (FAK), a crucial downstream signaling
      molecule of beta1-integrin. Our findings suggest that GALNT2 is a critical
      initiating enzyme of O-glycosylation for regulating EVT invasion.

PMID- 23117233
TI  - Three-step management of pneumothorax: time for a re-think on initial management.
AB  - Pneumothorax is a common disease worldwide, but surprisingly, its initial
      management remains controversial. There are some published guidelines for the
      management of spontaneous pneumothorax. However, they differ in some respects,
      particularly in initial management. In published trials, the objective of
      treatment has not been clarified and it is not possible to compare the treatment
      strategies between different trials because of inappropriate evaluations of the
      air leak. Therefore, there is a need to outline the optimal management strategy
      for pneumothorax. In this report, we systematically review published randomized
      controlled trials of the different treatments of primary spontaneous
      pneumothorax, point out controversial issues and finally propose a three-step
      strategy for the management of pneumothorax. There are three important
      characteristics of pneumothorax: potentially lethal respiratory dysfunction; air
      leak, which is the obvious cause of the disease; frequent recurrence. These three
      characteristics correspond to the three steps. The central idea of the strategy
      is that the lung should not be expanded rapidly, unless absolutely necessary. The
      primary objective of both simple aspiration and chest drainage should be the
      recovery of acute respiratory dysfunction or the avoidance of respiratory
      dysfunction and subsequent complications. We believe that this management
      strategy is simple and clinically relevant and not dependent on the
      classification of pneumothorax.

PMID- 23117234
TI  - Comparison of radial deformability of stent posts of different aortic
      bioprostheses.
AB  - OBJECTIVES: Little is known about the stent deformability required for optimal
      stented heart valve bioprosthesis design. Therefore, two bioprosthetic valves
      with known good long-term clinical results were tested. The strain in the radial
      direction of the stent posts of these valves was compared with contemporary
      bioprosthetic valves and a native porcine aortic root. METHODS: Medtronic Intact
      and Carpentier-Edwards Standard (CES), and four contemporary bioprostheses,
      including one self-expanding prosthesis, were tested with three sonomicrometry
      probes per valve fixed at commissure attachment points. The mean values from 2400
      data points from three measurements of the interprobe distances were used to
      calculate the radius of the circle circumscribed around the three probes. Changes
      in the radius of the aortic root at pressures 70-90 and 120-140 mmHg (pressure
      during diastole and systole) and that of the stent posts at 70-90 and 0-10 mmHg
      (transvalvular pressure gradient during diastole and systole) were compared.
      RESULTS: An increase in radius by 7.3 +/- 2.6, 8.7 +/- 0.0 and 3.9 +/- 0.0% for
      the porcine aortic root, CES and Intact valves, respectively, was observed during
      transition from diastolic to systolic pressure and less for contemporary
      bioprostheses-mean 2.5 +/- 0.9%, lowest 1.2 +/- 0.0. CONCLUSIONS: The results
      indicate that the radial deformability of bioprosthetic valve stent posts can be
      as low as 1.2% for xenoaortic and 3.0% for xenopericardial prostheses with no
      compromise of valve durability. Although these results suggest that valve stent
      post-deformability might not be of critical importance, a concrete answer to the
      question of the significance of stent deformability for valve durability can be
      obtained only by acquiring long-term follow-up results for valve prostheses with
      rigid stents.

PMID- 23117236
TI  - Wavering calcified amorphous tumour of the heart in a haemodialysis patient.
AB  - Calcified amorphous tumour is a rare, non-neoplastic, endocardially based,
      intracavitary cardiac mass. This report describes a 59-year old man in whom a
      mobile mass was found incidentally in the heart by routine echocardiography after
      he had been on haemodialysis for 3 years. Transoesophageal echocardiography
      revealed a high-echoic swinging tumour that originated from the annulus of the
      anterior commissure of the mitral valve. Surgical resection was performed to
      prevent embolization, and his clinical course was excellent.

PMID- 23117235
TI  - Morbidity, mortality and survival after 110 consecutive bilobectomies over 12
      years.
AB  - OBJECTIVES: To analyse statistical aspects of mortality, morbidity and survival
      after bilobectomy (BT), an operation rarely studied in the literature. METHODS:
      One hundred and ten cases were studied, comprising 58 upper-middle bilobectomies
      and 52 lower-middle bilobectomies performed between 1999 and 2010. Indications
      were of 9 benign diseases, 12 carcinoid tumours, 5 metastases and 84 non-small
      cell lung cancers (2 stage 0; 34 stage I; 22 stage II; 25 stage III and 1 stage
      IV). RESULTS: Mortality was nil. Twenty-six percent of patients experienced
      significant morbidity, influenced in multivariate analysis by the presence of
      three or more comorbidities (P = 0.03) and by a forced expiratory volume in 1 s
      of <60% (P = 0.01). Lower-middle BT was associated with more postoperative
      complications than upper-middle BT (P = 0.012). The 5-year survival rate of
      patients with non-small cell lung carcinoma was 82% in stage I, 59% in stage II
      and 20% in stage IIIA. Survival was significantly influenced by stage (P =
      0.0018) and tobacco weaning (P = 0.0012). CONCLUSIONS: BT can be achieved with
      low mortality, and survival results that are comparable with those unregistered
      after standard lobectomy. However, almost one quarter of patients experienced
      significant postoperative complications. Surgical techniques aiming to reduce
      residual pleural space should be especially considered after lower-middle BT, due
      to the highest morbidity being associated with this procedure.

PMID- 23117237
TI  - Screening children for autism in an urban clinic using an electronic M-CHAT.
AB  - BACKGROUND: The Modified Checklist for Autism in Toddlers (M-CHAT) is a screening
      tool for autism spectrum disorders in the clinic. However, the follow-up
      questions in the M-CHAT are difficult to implement on a paper format. OBJECTIVE:
      To compare the effectiveness of the M-CHAT on an electronic format versus paper
      format in an outpatient clinic setting. Methods. A prospective study used
      electronic M-CHAT on the iPad. A retrospective review of paper M-CHATs 6 months
      prior to implementation was used as the comparison group. RESULTS: A total of 176
      participants completed the electronic M-CHAT format and 197 paper M-CHATs were
      retrospectively reviewed. The electronic format (3%) resulted in a significant
      difference in the frequency of children found to be at risk for autism compared
      with the paper version (11%); 99% of parents rated the experience as "good" or
      "excellent." CONCLUSION: The electronic format lowered both false at-risk screens
      and false not-at-risk screens and had higher parental satisfaction.

PMID- 23117238
TI  - Ten-week-old girl with lethargy, weakness, and poor feeding.

PMID- 23117239
TI  - Toilet training method is not related to dysfunctional voiding.
AB  - BACKGROUND: Toilet training is an important marker of physical and psychosocial
      development, but the best strategy for implementing training is still unknown.
      The purpose of this study is to compare dysfunctional voiding outcomes for 2
      common toilet training strategies: parent-oriented training and child-oriented
      training. MATERIALS AND METHODS: This study was completed using a case-control
      design, with participants between the ages of 4 and 12 years. All participants
      were asked to complete questionnaires related to demographics and toilet training
      method. Results were then analyzed between cases and controls. RESULTS: In all,
      215 patients with a mean age 7.76 years participated in this study. Cases and
      controls showed no significant difference for demographic measures and
      socioeconomic status. Furthermore, there was no significant difference in
      dysfunctional voiding between toilet training methods. CONCLUSION: Toilet
      training method does not seem to have any long-term effect on dysfunctional
      voiding. As such, clinicians should advise parents that both methods are
      acceptable.

PMID- 23117240
TI  - Fever of unknown origin in a child.

PMID- 23117241
TI  - Autophagy contributes to inflammation in patients with TNFR-associated periodic
      syndrome (TRAPS).
AB  - OBJECTIVES: Tumour necrosis factor (TNF) receptor-associated periodic syndrome
      (TRAPS) is caused by TNFRSF1A mutations, known to induce intracellular retention
      of the TNFalpha receptor 1 (TNFR1) protein, defective TNFalpha-induced apoptosis,
      and production of reactive oxygen species. As downregulation of autophagy, the
      main cellular pathway involved in insoluble aggregate elimination, has been
      observed to increase the inflammatory response, we investigated whether it plays
      a role in TRAPS pathogenesis. METHODS: The possible link between TNFRSF1A
      mutations and inflammation in TRAPS was studied in HEK-293T cells, transfected
      with expression constructs for wild-type and mutant TNFR1 proteins, and in
      monocytes derived from patients with TRAPS, by investigating autophagy function,
      NF-kappaB activation and interleukin (IL)-1beta secretion. RESULTS: We found that
      autophagy is responsible for clearance of wild-type TNFR1, but when TNFR1 is
      mutated, the autophagy process is defective, probably accounting for mutant TNFR1
      accumulation as well as TRAPS-associated induction of NF-kappaB activity and
      excessive IL-1beta secretion, leading to chronic inflammation. Autophagy
      inhibition due to TNFR1 mutant proteins can be reversed, as demonstrated by the
      effects of the antibiotic geldanamycin, which was found to rescue the membrane
      localisation of mutant TNFR1 proteins, reduce their accumulation and counteract
      the increased inflammation by decreasing IL-1beta secretion. CONCLUSIONS:
      Autophagy appears to be an important mechanism in the pathogenesis of TRAPS, an
      observation that provides a rationale for the most effective therapy in this
      autoinflammatory disorder. Our findings also suggest that autophagy could be
      proposed as a novel therapeutic target for TRAPS and possibly other similar
      diseases.

PMID- 23117242
TI  - IFNalpha and its response proteins, IP-10 and SIGLEC-1, are biomarkers of disease
      activity in systemic lupus erythematosus.
AB  - OBJECTIVES: To evaluate and compare the clinical efficacy of three biomarkers for
      interferon (IFN) activity (measured directly and indirectly) and six traditional
      biomarkers in indicating current and prospective disease activity (DA) in
      systemic lupus erythematosus (SLE). METHODS: IFNalpha (dissociation-enhanced
      lanthanide fluorescent immunoassay), IFNgamma-inducible protein 10 (IP-10)
      (ELISA) and sialic acid-binding Ig-like lectin 1 (SIGLEC-1) (flow cytometry) were
      measured in 79 accurately characterised patients with lupus and compared with
      serum titres of Anti-dsDNA (ELISA and radioimmunoassay), Anti-dsDNA-NcX ELISA,
      Anti-Nuc ELISA, and complement C3 and C4. DA was evaluated using the British
      Isles Lupus Assessment Group 2004 Index (BILAG-2004) and a modified SLE Disease
      Activity Index-2000 (mSLEDAI-2K). In addition, 31 clinically quiescent patients
      were monitored for flares over the course of 180 days. RESULTS: Increased levels
      of IFNalpha, IP-10 and SIGLEC-1 were found in 32%, 50% and 86%, respectively, of
      66 patients with active SLE. IFNalpha (r=0.45; p<0.0001) and SIGLEC-1 (r=0.54;
      p<0.0001) correlated better with BILAG-2004 than did IP-10 (r=0.38; p=0.0002),
      Farr assay (r=0.40; p=0.0001), Anti-dsDNA-NcX ELISA (r=0.28; p=0.0061), Anti
      dsDNA ELISA (r=0.31; p=0.0025), Anti-Nuc ELISA (r=0.25; p=0.0121), C3 (r=-0.43;
      p<0.0001) and C4 (r=-0.33; p=0.0013). Predictors of SLE flares were disease
      duration <=92 months, mild clinical activity (in contrast with no activity),
      complement C3<=89 mg/dl and IFNalpha>=20 pg/ml, while only lymphocyte count and
      age were independent predictors in multivariate analysis. CONCLUSIONS: IFNalpha,
      IP-10 and SIGLEC-1 emerged as beneficial biomarkers of DA in patients with SLE.
      Therefore the implementation of IFN biomarkers in standard lupus diagnostics
      should be reappraised, especially in view of emerging anti-IFN-directed
      therapies.

PMID- 23117243
TI  - Response to glucocorticoids at 2 weeks predicts the effectiveness of DMARD
      induction therapy at 3 months: post hoc analyses from the tREACH study.
AB  - OBJECTIVE: To investigate if a glucocorticoid (GC) response at 2 weeks, defined
      by EULAR response criteria, can predict active disease (Disease Activity Score
      (DAS)>2.4) at 3 months. METHODS: For this study, data of the Treatment in the
      Rotterdam Early Arthritis Cohort study (tREACH), an ongoing clinical trial that
      evaluates different induction therapies in early rheumatoid arthritis, were used.
      We selected patients who had a high probability of progressing to persistent
      arthritis (>70% based on the prediction model of Visser). All patients within the
      high-probability stratum, who had a baseline DAS>2.2 and a DAS assessment at 2
      weeks after randomisation, were included (n=120). Besides GC response at 2 weeks,
      we investigated which other factors were associated with active disease (DAS>2.4)
      after 3 months of disease-modifying antirheumatic drug (DMARD) treatment. All
      variables with a p<=0.25 were assessed in our logistic regression model with
      backward selection. Variables were eliminated until all remaining variables had a
      significant association (p<0.05). RESULTS: Patients who did not respond to GC
      bridging therapy at 2 weeks had an overall OR of having active disease at 3
      months of 10.29 (95% CI 3.34 to 31.64; p<0.001) in comparison with responders.
      The corrected OR was 14.00 (95% CI 3.31 to 59.21; p<0.001). Our final model
      predicting response at 3 months included the following variables: gender, GC
      response, induction therapy arms and baseline DAS, which had an explained
      variance of 39%. CONCLUSIONS: GC response at 2 weeks is a useful tool for
      recognising those patients who will probably have active disease (DAS>2.4) after
      3 months of DMARD treatment.

PMID- 23117244
TI  - Healthcare service utilisation costs are reduced when rheumatoid arthritis
      patients achieve sustained remission.
AB  - OBJECTIVE: Determine healthcare service utilisation costs among patients using
      biological therapies for rheumatoid arthritis (RA), considering the magnitude and
      duration of patient response achieved. METHODS: Clinical data from the Alberta
      Biologics Pharmacosurveillance Program (ABioPharm) was linked with provincial
      physician billing claims, outpatient visits and hospitalisations. The annual mean
      healthcare service utilisation costs (total, RA-attributable, non-RA
      attributable) were estimated for patients during the best disease activity level
      reached during treatment. RESULTS: Of 1086 patients: 16% achieved DAS28 remission
      >1 year, 37% had a DAS28 remission period <1 year, 13% had a low disease activity
      (LDA) period <1 year and 31% had persistent moderate or high disease activity.
      Mean annual healthcare service utilisation cost savings for those in sustained
      remission was $2391 (95% CI 1437 to 3909, p<0.001) and $2104 (95% CI 838 to 3512,
      p<0.001) for those with non-sustained LDA, relative to the persistent disease
      activity group. Savings were also observed for those in sustained remission
      compared to non-sustained remission (annual savings $1422, 95% CI 564 to 2796,
      p<0.001). RA-related costs were consistent across disease activity and cost
      categories; the majority of costs were attributable to non-RA related
      hospitalisations. CONCLUSIONS: We provide evidence of economic benefits to the
      healthcare system when RA patients achieve persistent good disease control.
      Benefits from brief periods of remission and LDA are also observed. Coupled with
      an expected increase in productivity from improved disease control, there is
      societal benefit to the utilisation of biologics in RA management to achieve
      treatment goals.

PMID- 23117246
TI  - The nuclear factor-kappaB correlates with increased expression of interleukin-6
      and promotes progression of gastric carcinoma.
AB  - The interleukin-6 (IL-6) pathway is one of the mechanisms that link inflammation
      and angiogenesis with malignancy. Since nuclear factor-kappaB (NF-kappaB) is a
      potential sign for inflammation, NF-kappaB has been associated with the
      progression of disease in various types of cancer. In the present study, we
      investigated the effect of NF-kappaB on the IL-6 pathway in gastric carcinoma and
      their correlation with disease status and prognosis. The mRNA and protein levels
      of NF-kappaB, IL-6 and vascular endothelial growth factor (VEGF) were detected by
      western blotting and reverse transcription (RT) quantitative PCR (RT-qPCR). Using
      immunohistochemistry, we examined the expression of these proteins in normal and
      human gastric cancer tissue samples. The concentrations of IL-6 and TNF-alpha in
      collected blood samples were measured according to the enzyme-linked
      immunosorbent assay (ELISA). IL-6 and TNF-alpha were found to be expressed at
      high levels in human gastric cancer samples. A positive correlation was found
      between the expression of IL-6 and NF-kappaB by immunohistochemical and further
      correlation analysis. IL-6, NF-kappaB and VEGF protein and mRNA levels increased
      significantly in gastric cancer tissue compared with those in adjacent normal
      mucosa tissue samples. In conclusion, our findings demonstrate that NF-kappaB, IL
      6 and VEGF mRNA and protein levels increase significantly in gastric cancer
      tissues. In addition, the expression of NF-kappaB was positively correlated with
      the expression of IL-6 according to immunohistochemical and further correlation
      analysis, which suggests that the suppression of NF-kappaB or IL-6 may be a
      potential target for clinical therapy of gastric cancer in the future.

PMID- 23117245
TI  - Efficacy and safety of strontium ranelate in the treatment of knee
      osteoarthritis: results of a double-blind, randomised placebo-controlled trial.
AB  - BACKGROUND: Strontium ranelate is currently used for osteoporosis. The
      international, double-blind, randomised, placebo-controlled Strontium ranelate
      Efficacy in Knee OsteoarthrItis triAl evaluated its effect on radiological
      progression of knee osteoarthritis. METHODS: Patients with knee osteoarthritis
      (Kellgren and Lawrence grade 2 or 3, and joint space width (JSW) 2.5-5 mm) were
      randomly allocated to strontium ranelate 1 g/day (n=558), 2 g/day (n=566) or
      placebo (n=559). The primary endpoint was radiographical change in JSW (medial
      tibiofemoral compartment) over 3 years versus placebo. Secondary endpoints
      included radiological progression, Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC) score, and knee pain. The trial is registered
      (ISRCTN41323372). RESULTS: The intention-to-treat population included 1371
      patients. Treatment with strontium ranelate was associated with smaller
      degradations in JSW than placebo (1 g/day: -0.23 (SD 0.56) mm; 2 g/day: -0.27 (SD
      0.63) mm; placebo: -0.37 (SD 0.59) mm); treatment-placebo differences were 0.14
      (SE 0.04), 95% CI 0.05 to 0.23, p<0.001 for 1 g/day and 0.10 (SE 0.04), 95% CI
      0.02 to 0.19, p=0.018 for 2 g/day. Fewer radiological progressors were observed
      with strontium ranelate (p<0.001 and p=0.012 for 1 and 2 g/day). There were
      greater reductions in total WOMAC score (p=0.045), pain subscore (p=0.028),
      physical function subscore (p=0.099) and knee pain (p=0.065) with strontium
      ranelate 2 g/day. Strontium ranelate was well tolerated. CONCLUSIONS: Treatment
      with strontium ranelate 1 and 2 g/day is associated with a significant effect on
      structure in patients with knee osteoarthritis, and a beneficial effect on
      symptoms for strontium ranelate 2 g/day.

PMID- 23117248
TI  - Medical treatment of idiopathic heavy menstrual bleeding. What is new? An
      evidence based approach.
AB  - BACKGROUND: Heavy menstrual bleeding (HMB) is an important health problem
      affecting up to 30 % of reproductive age women, interfering with their quality of
      life. Medical therapy, with the avoidance of unnecessary surgery, is an
      attractive option. PURPOSE: To provide a comprehensive review of the current
      medical treatments available for idiopathic HMB and to focus on the newly
      introduced modalities. Furthermore, to provide a practical algorithm based on the
      best available evidence. METHODS: A PubMed search was conducted looking for the
      different trials, reviews and various guidelines relating to medical treatment of
      idiopathic HMB. RESULTS: The most effective medical treatment for idiopathic HMB
      is the levonorgestrel-releasing intrauterine system. It provides a reliable long
      term effect. Importantly, there is a growing scientific evidence for new
      modalities entailing; modified-release formulation of tranexamic acid, the new
      four-phasic estradiol valerate/dienogest contraceptive pills and combined
      contraceptive vaginal ring. Also, vaginal danazol has been tried. CONCLUSION:
      Maintenance of status quo, i.e., keeping first-line treatment of idiopathic HMB
      as medical treatment is an essential issue. Modified-release formulation of
      tranexamic acid, the new four-phasic contraceptive pills and contraceptive
      vaginal ring are recently added to the medical armamentarium for treatment of
      idiopathic HMB increasing its efficacy.

PMID- 23117247
TI  - A low cost setup for behavioral audiometry in rodents.
AB  - In auditory animal research it is crucial to have precise information about basic
      hearing parameters of the animal subjects that are involved in the experiments.
      Such parameters may be physiological response characteristics of the auditory
      pathway, e.g. via brainstem audiometry (BERA). But these methods allow only
      indirect and uncertain extrapolations about the auditory percept that corresponds
      to these physiological parameters. To assess the perceptual level of hearing,
      behavioral methods have to be used. A potential problem with the use of
      behavioral methods for the description of perception in animal models is the fact
      that most of these methods involve some kind of learning paradigm before the
      subjects can be behaviorally tested, e.g. animals may have to learn to press a
      lever in response to a sound. As these learning paradigms change perception
      itself (1,2) they consequently will influence any result about perception
      obtained with these methods and therefore have to be interpreted with caution.
      Exceptions are paradigms that make use of reflex responses, because here no
      learning paradigms have to be carried out prior to perceptual testing. One such
      reflex response is the acoustic startle response (ASR) that can highly
      reproducibly be elicited with unexpected loud sounds in naive animals. This ASR
      in turn can be influenced by preceding sounds depending on the perceptibility of
      this preceding stimulus: Sounds well above hearing threshold will completely
      inhibit the amplitude of the ASR; sounds close to threshold will only slightly
      inhibit the ASR. This phenomenon is called pre-pulse inhibition (PPI) (3,4), and
      the amount of PPI on the ASR gradually depends on the perceptibility of the pre
      pulse. PPI of the ASR is therefore well suited to determine behavioral audiograms
      in naive, non-trained animals, to determine hearing impairments or even to detect
      possible subjective tinnitus percepts in these animals. In this paper we
      demonstrate the use of this method in a rodent model (cf. also ref. (5)), the
      Mongolian gerbil (Meriones unguiculatus), which is a well know model species for
      startle response research within the normal human hearing range (e.g. (6)).

PMID- 23117249
TI  - Clinical significance of ptyalism gravidarum.
AB  - OBJECTIVE: The aim of this study was to identify the clinical significance
      associated with ptyalism gravidarum in Japanese singleton pregnancies. METHODS:
      Data were collected from 22 patients complicated by ptyalism gravidarum whose
      symptoms continued until delivery and from 7,743 unaffected controls. RESULTS:
      The incidence of ptyalism gravidarum in the Japanese pregnant women was about 0.3
      %. Using multiple logistic regressions, ptyalism gravidarum was associated with
      history of hyperemesis gravidarum (p < 0.01), neonatal male sex (p = 0.02) and
      small for gestational age infants (p = 0.04). CONCLUSIONS: Ptyalism gravidarum
      may be a distinctive condition leading to adverse perinatal outcomes.

PMID- 23117251
TI  - Familial effects on survival after myocardial infarction: a registry-based sib
      pair study.
AB  - The chance of surviving an acute myocardial infarction (MI) has increased greatly
      but many persons still die as a consequence of MI. We assessed the familiality of
      suffering fatal MI using Swedish registry data. All 4,239 sib-pairs (n = 8,478)
      where both siblings had suffered an MI and who were born 1932 or later were
      identified by matching the Swedish National Patient-, Cause of Death and Multi
      Generation registries. The Cox proportional hazards model was used to estimate
      the association between survival times between sibling who had, or not had, a
      sibling who died within 28 days of their first MI. The risk estimate was adjusted
      for year of infarction, age at infarction, sex and county for both siblings. The
      mortality rate was increased the first 28 days after infarction amongst patients
      who had a sibling who also died within 28 days of infarction (adjusted Hazard
      ratio (HR) [95 % confidence interval [95 % CI]: 1.44 [1.18-1.75]). These patients
      also have a worse long-term survival (adjusted HR [95 % CI]: 1.65 [1.24-2.21]).
      There appears to be familial effects that influence MI survival. This may have
      important implications for MI prevention strategies but further studies are
      required to determine if these effects are due to genetic or environmental
      factors.

PMID- 23117252
TI  - Discriminating of ATP competitive Src kinase inhibitors and decoys using self
      organizing map and support vector machine.
AB  - A data set containing 686 Src kinase inhibitors and 1,941 Src kinase non-binding
      decoys was collected and used to build two classification models to distinguish
      inhibitors from decoys. The data set was randomly split into a training set (458
      inhibitors and 972 decoys) and a test set (228 inhibitors and 969 decoys). Each
      molecule was represented by five global molecular descriptors and 18 2D property
      autocorrelation descriptors calculated using the program ADRIANA.Code. Two
      machine learning methods, a Kohonen's self-organizing map (SOM) and a support
      vector machine (SVM), were utilized for the training and classification. For the
      test set, classification accuracy (ACC) of 99.92% and Matthews correlation
      coefficient (MCC) of 0.98 were achieved for the SOM model; ACC of 99.33% and MCC
      of 0.98 were obtained for the SVM model. Some molecular properties, such as
      molecular weight, number of atoms in a molecule, hydrogen bond properties,
      polarizabilities, electronegativities, and hydrophobicities, were found to be
      important for the inhibition of Src kinase.

PMID- 23117253
TI  - The LORS-enabled dialogue: a collaborative intervention to promote recovery from
      psychotic disorders.
AB  - OBJECTIVE: This study examined the effectiveness of the LORS-Enabled Dialogue
      (LED) in reducing the discrepancy between clinicians' and patients' ratings of
      the severity of symptoms of psychotic disorders, improving adherence to
      medication, and improving functioning. METHODS: The LED intervention addresses
      the discrepancy between a clinician's severity rating of 13 symptoms measured by
      the Levels of Recovery From Psychotic Disorders Scale (LORS-clinician) and a
      patient's severity rating (LORS-patient). A discrepancy in ratings (LORS
      discrepancy), which is conceptualized as a patient's lack of awareness of his or
      her symptoms, is used by the clinician as the focus of a brief motivational
      interviewing technique, the LED, to enhance recovery. Ninety adult inpatients or
      outpatients with psychotic disorders were randomly assigned to the LED
      intervention (N=50) or a control group (N=40). They were assessed on measures of
      symptom awareness (LORS-discrepancy), psychopathology (LORS-clinician, LORS
      patient, and the Positive and Negative Syndrome Scale [PANSS]), adherence to
      medication (Kemp Compliance Tool), and functioning at baseline and at four
      postbaseline monthly assessments. The LED intervention was provided weekly for
      inpatients and monthly for outpatients. RESULTS: Among LED intervention
      participants, a decrease in psychopathology, as measured by the PANSS and LORS
      clinician scores, and an improvement in functioning were noted, along with a
      decrease in LORS-discrepancy scores. CONCLUSIONS: The LED intervention appears to
      be an efficient and effective treatment to reduce the severity of psychotic
      symptoms and improve functioning among persons with psychotic disorders. Further
      study of this intervention in various populations and clinical settings is
      needed.

PMID- 23117254
TI  - Nanostructure characterization by a combined x-ray absorption/scanning force
      microscopy system.
AB  - A combined x-ray transmission and scanning force microscope setup (NanoXAS)
      recently installed at a dedicated beamline of the Swiss Light Source combines
      complementary experimental techniques to access chemical and physical sample
      properties with nanometer scale resolution. While scanning force microscopy
      probes physical properties such as sample topography, local mechanical
      properties, adhesion, electric and magnetic properties on lateral scales even
      down to atomic resolution, scanning transmission x-ray microscopy offers direct
      access to the local chemical composition, electronic structure and magnetization.
      Here we present three studies which underline the advantages of complementary
      access to nanoscale properties in prototype thin film samples.

PMID- 23117255
TI  - Peri-stent aneurysm formation following a stent implant for stenotic intracranial
      vertebral artery dissection: a technical report of two cases successfully treated
      with coil embolization.
AB  - INTRODUCTION: Although stenting for stenotic vertebral artery dissection (VAD)
      improves compromised blood flow, subsequent peri-stent aneurysm (PSA) formation
      is not well-known. We report two cases with PSA successfully treated with coil
      embolization. METHODS: Three patients with stenotic intracranial VAD underwent
      endovascular angioplasty at our institution because they had acute infarction in
      posterior circulation territory and clinical evidence of hemodynamic
      insufficiency. In two of three patients balloon angioplasty at first session
      failed to relieve the stenosis, and a coronary stent was implanted. Angiography
      immediately after stenting showed no abnormality in case 1 and minimal slit-like
      projection at proximal portion of the stent in case 2. RESULTS: Angiography
      obtained 16 months after the stenting revealed PSA in case 1. In case 2,
      angiography performed 3 months later showed that the projection at proximal
      portion enlarged and formed an aneurysm outside the stent. Because follow-up
      angiographies showed growth of the aneurysm in both cases, endovascular
      aneurysmal embolization was performed. We advanced a microcatheter into the
      aneurysm through the strut of existing stent and delivered detachable coils into
      the aneurysm lumen successfully in both cases. The post-procedural course was
      uneventful, and complete obliteration of aneurysm was confirmed on angiography in
      both cases. CONCLUSION: Stenting for stenotic intracranial VAD may result in
      delayed PSA; therefore, follow-up angiographies would be necessary after stenting
      for stenotic intracranial arterial dissection. Coil embolization through the
      stent strut would be a solution for enlarging PSA.

PMID- 23117256
TI  - Primary cough headache, primary exertional headache, and primary headache
      associated with sexual activity: a clinical and radiological study.
AB  - INTRODUCTION: The purposes of this study are to describe clinical features of
      primary cough headache, primary exertional headache, and primary headache
      associated with sexual activity and to evaluate potential association with
      abnormalities in the cerebral or cervical venous circulation. METHODS: This
      multicentre, observational, non-interventional consecutive cohort study included
      patients fulfilling ICHD-II criteria for primary cough headache (N = 10), primary
      exertional headache (N = 11), or primary headache associated with sexual activity
      (N = 20), as well as 16 headache-free controls. Each patient was evaluated
      clinically and underwent craniocervical MRV of the cranial circulation. All scans
      were interpreted centrally by blinded raters, using the Farb criteria proposed
      for idiopathic intracranial hypertension. Stenosis was defined as a Farb score <3
      in left or right transverse sinuses or jugular veins. RESULTS: In all primary
      headache groups, headaches were most frequently diffuse, severe, or very severe.
      Headache duration was significantly shorter in patients with cough headache
      (median 6.5 versus 20 and 60 min). An exploitable magnetic resonance venogram was
      obtained for 36 patients. Stenosis was detected in none of the control group, but
      in 5/7 patients with primary cough headache group, 2/10 patients with primary
      exertion headache, and 12/19 patients with primary headache associated with
      sexual activity. The frequency of stenosis was significantly different from the
      control group in the primary cough headache and primary headache associated with
      sexual activity groups. CONCLUSIONS: Headaches provoked by cough and sexual
      activity are possibly associated with venous abnormalities in a significant
      subgroup of affected patients. As the literature shows conflicting results, this
      venous stenosis can be considered as a promoting factor.

PMID- 23117258
TI  - Effect of balance training on postural stability in subjects with chronic ankle
      instability.
AB  - The lateral ligament complex of the ankle is a frequently injured structure in
      sports and recreational activities, which often results in chronic ankle
      instability (CAI). Balance exercise training has become a common component of
      clinical rehabilitation for CAI to address postural deficits. To determine the
      effect of balance training on postural stability, this critically appraised topic
      presents a summary and analysis of 4 relevant studies that address the
      effectiveness of balance training in subjects with CAI. Information about the
      methods and sources used in the article is provided. The findings imply that
      there is moderate evidence that 4-6 wk of balance training can enhance static and
      dynamic postural stability in subjects with CAI.

PMID- 23117257
TI  - Relationship between vertebral artery hypoplasia and posterior circulation stroke
      in Chinese patients.
AB  - INTRODUCTION: Vertebral artery hypoplasia (VAH), which has been found in about 10
      % of normal individuals, does not produce symptoms but may be associated with an
      increased risk of cerebral posterior circulation ischemic (PCI) stroke. The aims
      of this study were to determine the prevalence of VAH in Chinese patients with
      cerebral infarction and investigate whether VAH is an independent risk factor for
      PCI stroke. METHODS: The medical records of 841 Chinese stroke patients were
      reviewed retrospectively. All patients underwent either cervical contrast
      enhanced magnetic resonance angiography (CE-MRA) or cervical computed tomography
      angiography (CTA). There is no standard definition of VAH; we defined it as a
      vertebral artery < 2 mm in diameter and the whole artery was slim or absent on CE
      MRA or CTA. Univariate and multivariate logistic regression analyses were
      performed to identify significant independent risk factors for PCI stroke.
      RESULTS: There were 230 patients (27.3 %) diagnosed with PCI stroke and 91
      patients diagnosed with VAH (10.8 %). Multivariate logistic regression analysis
      showed that VAH, male gender, and stenosis of the posterior circulation were
      independent risk factors for PCI stroke. CONCLUSIONS: Our results show that VAH
      is not rare in Chinese patients with stroke and that its presence increases the
      risk of PCI stroke.

PMID- 23117259
TI  - Expanding the range of possibility: exploring the uncertainty in projecting ozone
      related health effects of climate change.

PMID- 23117260
TI  - Magnetic susceptibility based magnetic resonance estimation of micro-bubble size
      for the vertically upward bubbly flow.
AB  - The approach originally developed for the Nuclear Magnetic Resonance analysis of
      stable micro-bubbles is applied to studies of vertical bubbly flows. A very fast
      dispersion (diffusion) of water in bubbly flows extends the fast diffusion limit
      down to short (2-10 ms) measurement times, permitting the use of the simplified
      analytical expression to extract the micro-bubble size information both in bulk
      and spatially resolved. The observed strong bubble-induced reduction in T(2)(*)
      necessitates the use of very short encoding times and pure phase encoding methods
      to accurately measure the void fraction. There was an expected underestimation of
      bubble sizes at faster flow rates due to the limitations of the theory derived
      for small bubble sizes and non-interacting spherical bubbles (low void fractions
      and slow flow rates). This approach lends itself to studies of bubbly flows and
      cavitating media characterized by small bubble sizes and low void fractions.

PMID- 23117261
TI  - Crystal structure of [Eu(CyMe4-BTBP)2kappa2O,O'-(NO3)](NO3)2.n-C8H17OH and its
      structure in 1-octanol solution.
AB  - The structure of the [Eu(CyMe(4)-BTBP)(2)(NO(3))(n)]((3-n)+) complex in 1-octanol
      solution and solid state has been determined by EXAFS and X-ray crystallography.
      The crystal structure shows that 1-octanol binds only to the europium(III)
      coordinated BTBP molecules through weak van der Waals forces, making it the first
      indication of the role of the extraction solvent.

PMID- 23117262
TI  - Emerging roles of cadmium and heme oxygenase in type-2 diabetes and cancer
      susceptibility.
AB  - Many decades after an outbreak of severe cadmium poisoning, known as Itai-itai
      disease, cadmium continues to pose a significant threat to human health
      worldwide. This review provides an update on the effects of this environmental
      toxicant cadmium, observed in numerous populations despite modest exposure
      levels. In addition, it describes the current knowledge on the link between heme
      catabolism and glycolysis. It examines novel functions of heme oxygenase-2 (HO-2)
      that protect against type 2-diabetes and obesity, which have emerged from
      diabetic/obese phenotypes of the HO-2 knockout mouse model. Increased cancer
      susceptibility in type-2 diabetes has been noted in several large cohorts. This
      is a cause for concern, given the high prevalence of type-2 diabetes worldwide. A
      lifetime exposure to cadmium is associated with pre-diabetes, diabetes, and
      overall cancer mortality with sex-related differences in specific types of
      cancer. Liver and kidney are target organs for the toxic effects of cadmium.
      These two organs are central to the maintenance of blood glucose levels. Further,
      inhibition of gluconeogenesis is a known effect of heme, while cadmium has the
      propensity to alter heme catabolism. This raises the possibility that cadmium may
      mimic certain HO-2 deficiency conditions, resulting in diabetic symptoms.
      Intriguingly, evidence has emerged from a recent study to suggest the potential
      interaction and co-regulation of HO-2 with the key regulator of glycolysis: 6
      phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4). HO-2 could thus be
      critical to a metabolic switch to cancer-prone cells because the enzyme PFKFB and
      glycolysis are metabolic requirements for cell proliferation and resistance to
      apoptosis.

PMID- 23117263
TI  - Serum pepsinogens, gastrin-17 and Helicobacter pylori antibody in the residents
      of two cities in china with distinct mortality rates of gastric cancer.
AB  - Gastric cancer is one of the most common malignant tumors causing death in Fujian
      Province, China. However, the mortality of gastric cancer is greatly varied in
      different areas in Fujian; for example, the mortality in Changle City is 7.4
      times higher than that in Fuan City. In this study, we compared the differences
      in serological parameters, pepsinogen (PG) I, PG II, gastrin-17 (G-17), and
      Helicobacter pylori (H. pylori) antibody, between the two cities. It has been
      reported that low serum PG I is correlated with atrophic gastritis, a high-risk
      condition for developing gastric cancer, while high serum G-17 has been used for
      serological detection of atrophic corpus gastritis. We recruited 224 healthy
      subjects in Changle and 229 healthy subjects in Fuan, matched in age and sex. The
      serum levels of PG II and G-17 were significantly higher in Changle than those in
      Fuan. Importantly, the frequency of the subjects with low serum PG I (< 25 MUg/L)
      was significantly higher in Changle than in Fuan, although the serum PG I levels
      were similar between the two cities. Moreover, the percentage of the subjects
      with high serum G-17 (>= 2 pmol/L) and the positive rate of serum IgG antibody
      against H. pylori were significantly higher in Changle than those in Fuan. The
      detected differences in these serological parameters are consistent with the
      notion that the prevalence of atrophic gastritis may be higher in Changle than in
      Fuan, which results in a higher risk condition for developing gastric cancer in
      Changle.

PMID- 23117264
TI  - Splenic irradiation as a component of a reduced-intensity conditioning regimen
      for hematopoietic stem cell transplantation in myelofibrosis with massive
      splenomegaly.
AB  - Primary myelofibrosis is a hematologic neoplasm characterized by bone marrow
      fibrosis and extramedullary hematopoiesis. A similar clinical condition can occur
      at late stage of myeloproliferative neoplasms such as polycythemia vera and
      essential thrombocythemia. Although allogeneic hematopoietic stem cell
      transplantation (HSCT) is currently the only curative strategy for both
      conditions, massive splenomegaly frequently observed in patients with
      myelofibrosis is considered to be a risk factor for graft failure or engraftment
      delay after transplantation. A proportion of patients can benefit from
      splenectomy before transplantation but such procedures have been associated with
      substantial surgical morbidity. Here, we report two elderly patients with
      myelofibrosis who received scheduled splenic irradiation for massive splenomegaly
      immediately prior to allogeneic HSCT instead of undergoing splenectomy. The first
      patient was a 60-year-old woman who received peripheral blood stem cell
      transplantation for post-essential thrombocythemia myelofibrosis from an HLA
      identical sibling; the second patient was a 60-year-old man who received
      unrelated bone marrow transplantation for primary myelofibrosis. After receiving
      fractionated splenic irradiation and fludarabine-based reduced-intensity
      conditioning regimens, these patients showed remarkable reduction of their
      splenomegaly at the time of transplantation. They attained successful donor cell
      engraftment without severe complications related to splenic irradiation, while
      improvement in splenomegaly was durable. Our experience suggests that splenic
      irradiation before allogeneic HSCT might be a safe and effective alternative to
      splenectomy for myelofibrosis patients with massive splenomegaly in terms of
      reducing the risk of surgical morbidity.

PMID- 23117266
TI  - Early sonographic diagnosis and successful management of the sesamoid bone
      locking in the thumb.

PMID- 23117265
TI  - The emergence and dissemination of CTX-M-producing Escherichia coli sequence type
      131 causing community-onset bacteremia in Israel.
AB  - Community-onset bloodstream infections caused by extended-spectrum beta-lactamase
      producing Escherichia coli (ESBL-EC-COBSIs) were investigated over a 7-year
      period (2003-2009) in our institution. ESBL-EC-COBSI inclusion criteria were
      cefotaxime/ceftazidime non-susceptible blood isolates recovered during 48 h upon
      hospital admission. Forty-one isolates were molecularly characterized.
      Susceptibilities were determined (Vitek-2) and genotyping was performed
      [multilocus sequence typing (MLST)]. CTX-M genes were determined [polymerase
      chain reaction (PCR) and sequencing] and bla CTX-M-encoding plasmids (n = 10)
      were analyzed and compared. Phylogrouping and virulence genes were identified
      (PCR). The incidence rate of ESBL-EC-COBSIs has increased from 2.94 to 7.87
      cases/10,000 admissions. All isolates were multidrug-resistant (MDR), displaying
      co-resistance to ciprofloxacin (93 %), trimethoprim-sulfamethoxazole (85 %), and
      gentamicin (51 %). MLST identified ten sequence types (STs), of which five were
      novel. ST131 accounted for 66 % of the cases (27/41), and dominated over the
      years (prevalence of 25 % in 2003 and 85 % in 2009). All isolates carried CTX-M
      genes with the following prevalence: bla CTX-M-2 (6/8; 75 %) in 2003; bla CTX-M
      15 (9/13, 69 % in 2007); and bla CTX-M-15 (11/20, 55 %) and bla CTX-M-14 (7/20,
      35 %) in 2009. bla CTX-M-15- and bla CTX-M-14-encoding plasmids harbored by ST131
      differed. Of all isolates, 98 % belonged to virulent phylogroups B2 (28/41, 68 %)
      and D (12/41, 29 %), though ST131 isolates carried a higher number of virulence
      genes compared to other lineages (p < 0.05). The incidence of ESBL-EC-COBSIs
      increased 2.7-fold during the period 2003-2009. This increase appears to be
      related to the emergence and clonal expansion of bla CTX-M-15- or bla CTX-M-14
      carrying ST131. The superiority of this virulent lineage should be further
      explored.

PMID- 23117267
TI  - Frequency and reasons for return to acute care in patients with leukemia
      undergoing inpatient rehabilitation: a preliminary report.
AB  - OBJECTIVE: The aim of this study was to assess the frequency and reasons for
      return to the primary acute care service among patients with leukemia undergoing
      inpatient rehabilitation. DESIGN: This is a retrospective study of all patients
      with leukemia, myelodysplastic syndrome, aplastic anemia, or myelofibrosis
      admitted to inpatient rehabilitation at a tertiary referral-based cancer center
      between January 1, 2005, and April 10, 2012. Items analyzed from patient records
      included return to the primary acute care service with demographic information,
      leukemia characteristics, medications, hospital admission characteristics, and
      laboratory values. RESULTS: Two hundred twenty-five patients were admitted a
      total of 255 times. Ninety-three (37%) of the 255 leukemia inpatient
      rehabilitation admissions returned to the primary acute care service. Eighteen
      (19%) and 42 (45%) of the 93 patients died in the hospital and were discharged
      home, respectively. Statistically significant factors (P < 0.05) associated with
      return to the primary acute care service include peripheral blast percentage and
      the presence of an antifungal agent on the day of the inpatient rehabilitation
      transfer. Using additional two factors (platelet count and the presence of an
      antiviral agent, both P < 0.11), the Return to Primary-Leukemia Index was
      formulated. CONCLUSIONS: Patients with leukemia with the presence of circulating
      peripheral blasts and/or an antifungal agent may be at increased risk for return
      to the primary acute care service. The Return to Primary-Leukemia Index should be
      tested in prospective studies to determine its usefulness.

PMID- 23117269
TI  - Effectiveness of acute inpatient rehabilitation after left ventricular assist
      device placement.
AB  - Left ventricular assist device (LVAD) placement is becoming more common as a
      treatment of end-stage heart failure. People who have undergone placement of an
      LVAD typically have deficits with their activities of daily living as well as
      decreased strength from prolonged immobility. Patients often benefit from
      admission to acute inpatient rehabilitation before being discharged home. Few
      studies have examined the effectiveness of acute inpatient rehabilitation for
      people who have undergone placement of an LVAD. This study examines the admission
      and discharge functional independence measure scores of 20 people admitted to
      acute inpatient rehabilitation at an academic center after placement of an LVAD.
      Most patients had improved function after acute inpatient rehabilitation. The
      mean change in functional independence measure score was 22.05, and the mean
      length of stay was 11.6 days. This study shows that people who have undergone
      placement of an LVAD have improved function and ability to perform activities of
      daily living after admission to inpatient rehabilitation.

PMID- 23117268
TI  - The Uniform Data System for Medical Rehabilitation: report of patients with
      debility discharged from inpatient rehabilitation programs in 2000-2010.
AB  - OBJECTIVE: Benchmark data are provided for a national sample of patients who
      received inpatient rehabilitation for debility. DESIGN: Patients with debility
      from 830 inpatient rehabilitation facilities in the United States contributing to
      the Uniform Data System for Medical Rehabilitation from 2000 to 2010 were
      examined. Demographic information (age, marital status, sex, race/ethnicity,
      prehospital living setting, and discharge setting), hospital information (length
      of stay, program interruptions, payer, and codes for admitting diagnosis), and
      functional status (Functional Independence Measure [FIM] instrument ratings at
      admission and discharge, FIM change, and FIM efficiency) were analyzed. RESULTS:
      Data from 2000 to 2010 (N = 260,373) revealed a decrease in mean (SD) FIM total
      admission ratings from 73.9 (16.2) to 62.5 (15.8). The FIM total discharge
      ratings decreased from 95.0 (19.7) to 88.2 (19.8). Mean (SD) length of stay
      decreased from 14.3 (9.1) to 12.1 (6.2) days. The FIM efficiency (change/day)
      increased from 1.9 (1.7) to 2.4 (1.9). Discharge to community decreased from 80%
      to 75%. Acute care discharges accounted for 12% of the cases. Policy changes
      affecting classification, reimbursement, and/or documentation processes may have
      influenced the results. CONCLUSIONS: National data indicate that the number of
      debility cases is increasing with diverse composition of etiologic diagnoses. A
      high proportion of these patients is discharged to acute care compared with other
      impairment groups.

PMID- 23117270
TI  - Pregnancy leads to lasting changes in foot structure.
AB  - OBJECTIVE: Women are disproportionately affected by musculoskeletal disorders.
      Parous women seem to be at a particularly elevated risk for structural and
      functional changes in the lower limbs. The combination of increased weight on the
      joints with potentially greater laxity during pregnancy could lead to permanent
      structural changes in the feet. Although arches may become lax during pregnancy,
      it is unknown whether the changes persist. The objective of this study was to
      determine whether arch height loss persists postpartum. DESIGN: Forty-nine women
      completed this longitudinal study. Static and dynamic arch measurements were
      collected in the first trimester and at 19 wks postpartum. Linear mixed models
      were used to determine whether outcome measures significantly changed overall or
      by parity. RESULTS: Arch height and rigidity indices significantly decreased,
      with concomitant increases in foot length and arch drop. The first pregnancy
      accounted for the reduction in arch rigidity and the increases in foot length and
      arch drop. No changes were detected in the center of pressure excursion index.
      CONCLUSIONS: Pregnancy seems to be associated with a permanent loss of arch
      height, and the first pregnancy may be the most significant. These changes in the
      feet could contribute to the increased risk for musculoskeletal disorders in
      women. Further research should assess the efficacy of rehabilitative
      interventions for prevention of pregnancy-related arch drop.

PMID- 23117272
TI  - Autonomic dysreflexia and posterior reversible encephalopathy syndrome.
AB  - Autonomic dysreflexia is a syndrome of massive imbalanced reflex sympathetic
      discharge in patients who had a spinal cord injury above the splanchnic
      sympathetic outflow resulting in a sudden increase in blood pressure. Posterior
      reversible encephalopathy syndrome (PRES) refers to a clinicoradiologic entity
      characterized by headache, consciousness impairment, visual disturbances,
      seizures, and posterior transient changes on neuroimaging (cerebral vasogenic
      edema). Hypertension is a common cause of PRES. The authors describe two case
      reports of patients with tetraplegia who developed PRES after an autonomic
      dysreflexia episode. One of them had recurrence of PRES in a similar clinical
      context. The authors discuss further aspects of PRES and its recurrence, which
      seems to be unusual particularly after autonomic dysreflexia.

PMID- 23117271
TI  - Factors associated with total inpatient costs and length of stay during surgical
      hospitalization among veterans who underwent lower extremity amputation.
AB  - OBJECTIVE: The aim of this study was to identify patient- and facility-level
      factors associated with total inpatient costs and length of stay (LOS) among
      veterans who underwent lower extremity amputation. DESIGN: Patient data for 1536
      veterans were compiled from nine databases from the Veterans Health
      Administration between October 1, 2002, and September 30, 2003. Linear mixed
      models were used to identify the factors associated with the natural logarithm of
      total inpatient costs and LOS. RESULTS: Statistically significant factors
      associated with both higher total inpatient costs and longer LOS included
      admission by transfer from another hospital, systemic sepsis, arrhythmias,
      chronic blood loss anemia, fluid and electrolyte disorders, weight loss,
      specialized inpatient rehabilitation, and higher hospital bed counts. Device
      infection, coagulopathy, solid tumor without metastasis, Commission on
      Accreditation of Rehabilitation Facilities accreditation, and the Medicare Wage
      Index were associated with only higher total inpatient costs. The factors
      associated with only longer LOS included older age, not being married, previous
      amputation complication, congestive heart failure, deficiency anemias, and
      paralysis. CONCLUSIONS: Most drivers of total inpatient costs were similar to
      those that increased LOS, with a few exceptions. These findings may have
      implications for projecting future healthcare costs and thus could be important
      in efforts to reducing costs, understanding LOS, and refining payment and
      budgeting policies.

PMID- 23117273
TI  - Gastrocnemius muscle contracture after spinal cord injury: a longitudinal study.
AB  - OBJECTIVE: The aim of this study was to examine changes in passive length and
      stiffness of the gastrocnemius muscle-tendon unit in people after spinal cord
      injury. DESIGN: In a prospective longitudinal study, eight wheelchair-dependent
      participants with severe paralysis were assessed 3 and 12 mos after spinal cord
      injury. Passive torque-angle data were obtained as the ankle was slowly rotated
      through range at six knee angles. Differences in passive ankle torque-angle data
      recorded at different knee angles were used to derive passive length-tension
      curves of the gastrocnemius muscle-tendon unit. Ultrasound imaging was used to
      determine fascicle and tendon contributions to the muscle-tendon unit length
      tension curves. RESULTS: The participants had ankle contractures (mean [SD]
      maximum passive ankle dorsiflexion angle, 88 [9] degrees) 3 mos after spinal cord
      injury. Ankle range did not worsen significantly during the subsequent 9 mos
      (mean change, -5 degrees; 95% confidence interval, -16 to 6 degrees). There were
      no changes in the mean slack length or the stiffness of the gastrocnemius muscle
      tendon unit or in the slack lengths of the fascicles or the tendon between 3 and
      12 mos after spinal cord injury. There were no consistent patterns of the change
      in slack length or stiffness with the changes in ankle range in the data from the
      individual participants. CONCLUSIONS: This study, the first longitudinal study of
      muscle length and stiffness after spinal cord injury, showed that the length and
      the stiffness of the gastrocnemius did not change substantially between 3 and 12
      mos after injury.

PMID- 23117274
TI  - Indomethacin prevents post-ERCP pancreatitis in selected high-risk patients.

PMID- 23117275
TI  - Plasma and tissue proteomic prognostic factors of response in primary breast
      cancer patients receiving neoadjuvant chemotherapy.
AB  - A pathological complete response (pCR) after neoadjuvant chemotherapy is observed
      in approximately 20% of breast cancer patients. A proteomic analysis was
      performed on plasma and tumor tissue before treatment to evaluate its potential
      impact on the prediction of response. One hundred and forty-nine breast cancer
      patients eligible for neoadjuvant chemotherapy were included in the study between
      February 2004 and January 2009 at three centers. The proteomic analysis was
      performed using SELDI Technology (ProteinChip CM10 pH4, IMAC-Cu and H50). Three
      acquisition protocols were used according to the mass range. Plasma and tumor
      proteomic signatures were generated using generalized ROC criteria and cross
      validation. Twenty-eight (18.8%) patients out of 149 experienced a pCR according
      to Sataloff criteria. In the cytosol analysis, respectively 4, 2 and 8 proteins
      had significantly different levels of expression in the responders and non
      responders using IMAC-Cu, H50 and CM10 pH4. Among the 8 proteins of interest on
      CM10 pH4, 2 (C1 and C7) were selected and were validated in 95.0 and 85.6% of the
      models. In the plasma analysis, respectively 12, 6 and 2 proteins had different
      levels of expression using the same proteinchips. Among the 12 plasma proteins of
      interest on IMAC-Cu, 2 (P1 and P7) were selected and were validated in 94.8 and
      97.6% of the models. A combined proteomic signature was generated, which remained
      statistically significant when adjusted for hormone receptor status and Ki-67.
      Our results show that proteomic analysis can differentiate complete pathological
      responders in breast cancer patients after neoadjuvant chemotherapy.

PMID- 23117276
TI  - Comparison of recruitment manoeuvres in ventilated sheep with acute respiratory
      distress syndrome.
AB  - BACKGROUND: Recruitment manoeuvres are widely used in clinical practice to open
      the lung and prevent lung injury by derecruitment, although the evidence is still
      discussed. In this study two different recruitment manoeuvres were compared to no
      recruitment manoeuvres (control) in ventilated sheep with acute respiratory
      distress syndrome (ARDS), induced by lung lavage. METHODS: We performed a
      prospective, randomised study in 26 ventilated sheep with ARDS, to evaluate the
      effect of two different recruitment manoeuvres on gas exchange, blood pressure
      and lung injury. The two different recruitment manoeuvres, the high pressure
      recruitment manoeuvre (HPRM), with high peak pressure, and the smooth and
      moderate recruitment manoeuvre (SMRM), with lower peak pressure, were compared to
      controls (no recruitment) after disconnection. Oxygenation index and ventilation
      efficacy index were calculated to evaluate gas exchange. Lung injury was assessed
      by inflammatory response in broncho-alveolar lavage fluid (BALF) and blood and
      histology of the lung. RESULTS: Oxygenation index improved significantly after
      both recruitment manoeuvres compared with controls, but no significant difference
      was found between the recruitment manoeuvres. Blood pressure decreased after HPRM
      but not after SMRM. HPRM induced a higher number of total cells and more
      neutrophils in the BALF. In the histology of the lung, mean alveolar size was
      increased in the dorsocranial region of the lung of SMRM compared to controls.
      CONCLUSION: Recruitment manoeuvres improved oxygenation, but SMRM was superior,
      with respect to hemodynamics and pulmonary inflammation, in ventilated sheep
      suffering from ARDS induced by lung lavage.

PMID- 23117277
TI  - A modern series of percutaneous intracavitary instillation of amphotericin B for
      the treatment of severe hemoptysis from pulmonary aspergilloma.
AB  - BACKGROUND: Pulmonary aspergillomas may cause life-threatening hemoptysis. The
      treatment of this condition is problematic because poor pulmonary function often
      precludes definitive surgical resection. METHODS: We retrospectively reviewed all
      patients hospitalized at our institution for hemoptysis associated with an
      aspergilloma over an 8-year period and who underwent percutaneous intracavitary
      instillation of amphotericin B (ICAB). ICAB consisted of catheter placement into
      the aspergilloma cavity with subsequent instillation of 50 mg amphotericin B in
      20 mL 5% dextrose solution daily for 10 days. RESULTS: ICAB was attempted for 23
      distinct episodes of severe hemoptysis in 20 individual patients. Catheter
      placement was successful in 21 of the 23 episodes (91%), and of these, ICAB
      instillation was successfully completed in 20 episodes (95%). In these 20
      episodes, hemoptysis ceased by hospital discharge in 17 of 20 patients (85%) and
      in all 18 who survived until a follow-up visit 1-month after treatment.
      Pneumothorax occurred in six of 23 (26%) catheter placement attempts without long
      term complications. Recurrence of serious hemoptysis occurred after six of 18
      episodes for which follow-up was available. Potential risk factors associated
      with severe, recurrent hemoptysis were a size increase or reappearance of the
      aspergilloma on a chest CT scan (P = .001), bleeding diathesis (P = .08), and
      lack of bronchial artery embolization during index hospitalization (P = .07).
      CONCLUSIONS: Our data suggest that ICAB is an effective short-term treatment to
      control severe hemoptysis caused by pulmonary aspergilloma. The long-term benefit
      of this procedure is unknown. We identified several potential risk factors for
      recurrent hemoptysis after ICAB that could be examined prospectively in future
      trials.

PMID- 23117278
TI  - Construction of triazolyl bidentate glycoligands (TBGs) by grafting of 3
      azidocoumarin to epimeric pyranoglycosides via a fluorogenic dual click reaction.
AB  - Glycoligands, which feature a glycoside as the central template incorporating
      Lewis bases as metal chelation sites and various fluorophores as the chemical
      reporter, represent a range of interesting scaffolds for development of
      chemosensors. Here, new types of triazolyl bidentate glycoligands (TBGs) based on
      the grafting of 3-azidocoumarin to the C2,3- or C4,6-positions of three epimeric
      pyranoglycosides including a glucoside, a galactoside, and a mannoside were
      efficiently synthesized via a fluorogenic dual click reaction assisted by
      microwave irradiation. The desired TBGs were afforded in high conversion rates
      (>90%) and reasonable yields (~70%). Moreover, a preliminary optical study of two
      hydroxyl-free glucoside-based TBGs indicates that these compounds are strongly
      fluorescent in pure water, implying their potential for ion detections in aqueous
      media.

PMID- 23117280
TI  - Photochemically induced radical alkynylation of C(sp3)-H bonds.
AB  - A general strategy for photochemical alkynylation of unreactive C(sp(3))-H bonds
      has been developed. After C-H abstraction by the photo-excited benzophenone, a
      two-carbon unit was efficiently transferred to the generated radical from 1-tosyl
      2-(trimethylsilyl)acetylene to afford the alkynylated product. The present
      reaction enables construction of various tri- and tetra-substituted carbons from
      heteroatom-substituted methylenes, methines and alkanes in a highly
      chemoselective fashion, and would serve as a new synthetic strategy for rapid
      construction of complex structures.

PMID- 23117279
TI  - Preparation of cell-lines for conditional knockdown of gene expression and
      measurement of the knockdown effects on E4orf4-induced cell death.
AB  - Functional inactivation of gene expression in mammalian cells is crucial for the
      study of the contribution of a protein of interest to various pathways(1,2).
      However, conditional knockdown of gene expression is required in cases when
      constitutive knockdown is not tolerated by cells for a long period of time(3-5).
      Here we describe a protocol for preparation of cell lines allowing conditional
      knockdown of subunits of the ACF chromatin remodeling factor. These cell lines
      facilitate the determination of the contribution of ACF to induction of cell
      death by the adenovirus E4orf4 protein(6). Sequences encoding short hairpin RNAs
      for the Acf1 and SNF2h subunits of the ACF chromatin remodeling factor were
      cloned next to a doxycycline-inducible promoter in a plasmid also containing a
      gene for the neomycin resistance gene. Neomycin-resistant cell clones were
      selected in the presence of G418 and isolated. The resulting cell lines were
      induced by doxycycline treatment, and once Acf1 or SNF2h expression levels were
      reduced, the cells were transfected with a plasmid encoding E4orf4 or an empty
      vector. To confirm the specific effect of the shRNA constructs, Acf1 or SNF2h
      protein levels were restored to WT levels by cotransfection with a plasmid
      expressing Acf1 or SNF2h which were rendered resistant to the shRNA by
      introduction of silent mutations. The ability of E4orf4 to induce cell death in
      the various samples was determined by a DAPI assay, in which the frequency of
      appearance of nuclei with apoptotic morphologies in the transfected cell
      population was measured(7-9). The protocol described here can be utilized for
      determination of the functional contribution of various proteins to induction of
      cell death by their protein partners in cases when constitutive knockdown may be
      cell lethal.

PMID- 23117281
TI  - Pars plana vitrectomy with medium-term postoperative perfluoro-N-octane for
      recurrent inferior retinal detachment complicated by advanced proliferative
      vitreoretinopathy.
AB  - PURPOSE: To describe a series of patients with recurrent inferior retinal
      detachment complicated by proliferative vitreoretinopathy (PVR) treated with pars
      plana vitrectomy and postoperative perfluoro-n-octane (PFO). METHODS: Consecutive
      patients with recurrent inferior retinal detachment and Grade C PVR were
      prospectively treated with 25-gauge pars plana vitrectomy and postoperative
      "medium-term" PFO for 2- to 3-week duration. All patients had subsequent PFO
      removal in a planned staged procedure. RESULTS: Forty-four eyes of 44 patients
      were included. Mean follow-up time was 30.71 +/- 12.92 months. Successful
      reattachment was achieved in 86% of eyes (38/44). Reattachment rates were
      statistically equivalent between eyes with and without previous scleral buckle.
      Reasons for redetachment were recurrent inferior PVR (four of six) and new
      superior break without PVR (two of six). Additional complications observed were
      cataract progression requiring surgery (42%), persistent intraocular pressure
      elevation (36%), and transient inflammation (32%). Macula-off status (P = 0.02)
      and persistent intraocular pressure elevation (P = 0.02) were factors associated
      with worse visual outcome. CONCLUSION: Medium-term PFO was found to be an
      efficacious technique for operative management of recurrent inferior retinal
      detachments complicated by Grade C PVR. The method of primary repair (scleral
      buckle vs. pars plana vitrectomy) did not affect reattachment rates. Transient
      inflammation and intraocular pressure elevation are potential complications
      associated with this technique. Persistent intraocular pressure elevation was
      associated with worse visual outcome.

PMID- 23117282
TI  - Engorgement of vortex vein and polypoidal choroidal vasculopathy.
AB  - PURPOSE: The purpose of this study was to identify a correlation between
      engorgement of the vortex vein and the development of polypoidal choroidal
      vasculopathy (PCV). METHODS: Engorgement of the vortex vein was evaluated by
      masked observers using a montage of indocyanine green angiography images. Sixty
      three eyes with PCV, 27 uninvolved fellow eyes with PCV, and 30 eyes of age
      matched control subjects were included. The incidence and distribution pattern of
      engorgement were evaluated. RESULTS: Thirty-three eyes (52.4%) of PCV evidenced
      engorgement of the vortex vein, whereas such engorgement was detected in only 7
      of the 30 eyes (30.4%) of the control subjects (P = 0.016). Among 27 fellow eyes
      with PCV, it was detected in 11 (40.7%) (P = 0.706 vs. control eyes). In all
      groups, it was most frequently detected at the inferior temporal quadrant. In
      eyes with PCV, mean (+/-standard deviation) choroidal thickness of the eyes
      evidencing vortex vein engorgement was 338.1 +/- 131.3 MUm and the thickness of
      those not evidencing vortex vein engorgement was 275.1 +/- 107.7 MUm. When the
      choroidal thickness increased to 10 MUm in the eyes with PCV, the odds of
      detecting the engorgement was multiplied by a factor of 1.05 (P = 0.042). The
      incidence of the engorgement of vortex vein was correlated with the presence of
      choroidal vascular hyperpermeability (P = 0.009). CONCLUSION: This study
      demonstrates that engorgement of the vortex vein was observed more frequently in
      the eyes with PCV. Such a finding was associated with choroidal thickening and
      choroidal vascular hyperpermeability. These indicate that the engorgement of the
      vortex vein might be involved in the pathogenic mechanisms of PCV.

PMID- 23117283
TI  - Suppression of IGHG1 gene expression by siRNA leads to growth inhibition and
      apoptosis induction in human prostate cancer cell.
AB  - To investigate the immunoglobulin G (IgG) expression in prostate cancer cell
      lines and explore the effects of IGHG1 gene knockdown on PC3 cell growth and
      apoptosis. Flow cytometry, qPCR and western blot were used to demonstrate IgG
      expression in prostate cancer cell lines. PC3 cells were transfected with
      designed siRNA, the expression of IgG was determined by qPCR and western blot,
      the proliferation and apoptosis were detected by 3-(4,5-dimethylthiazol-2-yl)-5
      (3-carboxymethoxy-phenyl)-2-(4-sulfophenil)-2H-tetrazolium, inner salt (MTS) and
      flow cytometry. The percentages of IgG in LNCaP cell membrane and cytoplasm were
      2.96 and 89.22 % by flow cytometer, those of PC3 cell were 86.73 and 90.99 %
      respectively. The average level of IgG1 mRNA expression in PC3 cell line was
      significantly higher than that in LNCaP cell line (3.08 +/- 0.15 vs 1.00 +/-
      0.37, P = 0.001). The protein level of IgG expression of PC3 cell line was 1.92
      +/- 0.15, compared with LNCaP cell line (1.05 +/- 0.86). The expression of IgG1
      mRNA and protein level in transfected PC3 cells decreased, with significant
      statistical differences from the blank control group (P < 0.01). The PC3 cell
      growth inhibition rates were 31.3 and 43.3 % in 48 and 72 h respectively. The
      rate of apoptotic PC3 cells were 5.29 +/- 0.41 % in experimental group higher
      than that in control group (1.49 +/- 0.29 %) (P < 0.01). IgG was identified in
      prostate cancer cells, and the siRNA targeted silencing of IGHG1 can inhibit cell
      viability and promote apoptosis, which might therefore act as a potential target
      in prostate cancer gene therapy.

PMID- 23117284
TI  - DNA polymerase beta promoter mutations affect gene transcription, translation and
      the sensitivity of esophageal cancer cells to cisplatin treatment.
AB  - The ability of a promoter to initiate transcription is important for the control
      of gene expression. Mutations in the DNA polymerase beta (po1beta) promoter may
      affect the transcription of this gene; however, the relationship between these
      mutations and the upregulation of the expression of po1beta remains unclear.
      Therefore, in the present study, three po1beta promoter mutants (M1, -37 C->A;
      M2, -114 G->A, -37 C->A; M3, -194 T->C) were generated to examine the effect of
      promoter mutations on polbeta gene expression and sensitivity to cisplatin. We
      found that the M1 and M2 mutant polbeta promoter constructs showed higher RLA
      than the wild-type polbeta promoter (P < 0.01), whereas the activity of the M3
      polbeta promoter did not differ significantly from that of the wild-type polbeta
      promoter (P > 0.05). The expression levels of polbeta mRNA and protein were
      significantly higher (P < 0.01) and the sensitivity to cisplatin was
      significantly lower (P < 0.05) in Eca9706(-/-)-M1 and Eca9706(-/-)-M2 cells than
      in Eca9706(-/-)-W. The expression levels of polbeta mRNA and protein and the
      sensitivity to cisplatin were not significantly different between Eca9706(-/-)-M3
      and Eca9706(-/-)-W cells (P > 0.05).These results revealed that specific
      mutations of the polymerase beta gene promoter significantly enhanced the gene's
      transcriptional activity. These mutations correspondingly increased the gene's
      mRNA and protein product, at the same time reduced the esophageal cancer cells'
      sensitivity to cisplatin.

PMID- 23117285
TI  - Monitoring veterans for metabolic side effects when prescribing antipsychotics.
AB  - OBJECTIVE: This study examined practices for monitoring metabolic side effects of
      antipsychotics at 32 Veterans Affairs (VA) facilities. METHODS: This
      retrospective cohort analysis included outpatients receiving a new antipsychotic
      prescription from April 2008 through March 2009 in Veterans Integrated Service
      Networks 18-22 (N=12,009). Data from national and regional VA data sources were
      used to examine the extent to which weight, glucose (or hemoglobin A1c), and low
      density lipoprotein (LDL) cholesterol were monitored within 30 days of the new
      prescription (baseline) and 60-120 days thereafter, consistent with American
      Diabetes and American Psychiatric Association consensus recommendations. Repeated
      measures analysis using the generalized estimating equation for binary variables
      examined the association of patient characteristics with likelihood of
      monitoring. RESULTS: Monitoring of the three metabolic parameters was
      significantly greater at baseline than at follow-up (p<.001). Weight was the most
      frequently monitored parameter. Having a diagnosis of diabetes or dyslipidemia
      was significantly associated with greater monitoring rates. Although monitoring
      rates did not vary significantly by psychiatric diagnosis, patients without a
      psychiatric diagnosis were less likely to be monitored than those with
      schizophrenia. Compared with patients taking antipsychotics with the lowest
      metabolic risk, those taking high-risk antipsychotics were more likely to have
      weight monitored at baseline (adjusted odds ratio [AOR]=1.20), whereas patients
      prescribed medium-risk antipsychotics were more likely to be monitored at
      baseline for glucose (AOR=1.12) and LDL (AOR=1.11). CONCLUSIONS: Efforts to
      improve monitoring of antipsychotics' metabolic side effects are needed and
      should be applied for all patients regardless of diagnosis.

PMID- 23117286
TI  - Incidence of decreased hip range of motion in youth soccer players and response
      to a stretching program: a randomized clinical trial.
AB  - CONTEXT: After years of focusing on the management of anterior cruciate ligament
      (ACL) injuries, the most common soccer-related injuries, the orthopedic community
      has concluded that soccer players have a wide range of variation in joint
      biomechanics and has thus started to focus research efforts on the morphological
      factors that might contribute to ACL trauma. One such factor is decreased hip
      rotation range of motion (ROM), which may be due to compensatory musculoskeletal
      changes occurring in response to longstanding soccer practice since childhood.
      OBJECTIVE: This study sought to assess decreased hip rotation and the influence
      of stretching exercises on the behavior of the hip joint in players of the youth
      soccer categories of a Brazilian soccer team. DESIGN: Randomized clinical trial.
      SETTING: University hospital. PATIENTS: 262 male soccer players. INTERVENTIONS:
      Subjects were randomly allocated into 2 groups-control or a stretching program.
      MAIN OUTCOME MEASURES: Subjects were reassessed after 12 wk. RESULTS: The
      findings suggest that hip-rotation ROM decreases over the years in soccer
      players. In the study sample, adherence to a stretching program improved only
      external hip-rotation ROM in the nondominant limb. CONCLUSION: Playing soccer can
      restrict rotation ROM of the hip, and adherence to stretching exercises may
      decrease the harmful effects on the hip joints.

PMID- 23117288
TI  - Proximity plus pollution: understanding factors in asthma among children living
      near major roadways.

PMID- 23117287
TI  - Surgical repair of left ventricular noncompaction in a patient with a novel
      mutation of the myosin heavy chain 7 gene.
AB  - Left ventricular noncompaction (LVNC) represents arrest of the normal myocardial
      compaction process and results in the persistence of multiple prominent
      ventricular trabeculations and deep intertrabecular recesses. LVNC can be
      classified into 2 forms: isolated LVNC in the absence of other cardiac anomalies
      and non-isolated LVNC associated with congenital heart disease. The clinical
      presentation and the natural history of LVNC are highly variable, ranging from no
      symptoms to congestive heart failure, arrhythmias, and systemic thromboemboli.
      LVNC is genetically heterogeneous and can be inherited as an autosomal dominant
      or X-linked recessive disorder. It is also linked to mutations in several genes,
      encoding the sarcomeric proteins, such as myosin heavy chain 7 (MYH7). MYH7
      encodes the beta-myosin heavy chain, expressed in the cardiac muscle. The
      operative indication for patients with non-isolated LVNC is unclear. Here, we
      report the first successful case of surgical repair of a ventricular septal
      defect (VSD) in an infant with non-isolated LVNC associated with a novel MYH7
      mutation. This mutation leads to the substitution of 7 amino acid residues (671
      677) in the actin-binding region of the protein. After the VSD operation, the
      patient's congestive heart failure and pulmonary hypertension improved. His
      condition has remained stable for 18 months with pharmacotherapy comprising
      diuretics, an angiotensin converting enzyme inhibitor, and a beta-blocker.
      Although the postsurgical observational period was short, the findings indicate
      that LVNC mutation analyses may facilitate surgical decisions and help predict
      clinical courses.

PMID- 23117289
TI  - A general synthesis of phosphaalkenes at zirconium with liberation of
      phosphaformamides.
AB  - A general, atom-economical method for the synthesis of phosphaalkenes is reported
      via the net coupling of primary alkyl or aryl phosphines with aryl or alkyl
      isocyanides at zirconium. The phosphorus-containing ligand can be liberated as
      the phosphaformamide from zirconium by reaction with an organic electrophile.

PMID- 23117290
TI  - Triangulated manifold meshing method preserving molecular surface topology.
AB  - Generation of manifold mesh is an urgent issue in mathematical simulations of
      biomolecule using boundary element methods (BEM) or finite element method (FEM).
      Defects, such as not closed mesh, intersection of elements and missing of small
      structures, exist in surface meshes generated by most of the current meshing
      method. Usually the molecular surface meshes produced by existing methods need to
      be revised carefully by third party software to ensure the surface represents a
      continuous manifold before being used in a BEM and FEM calculations. Based on the
      trace technique proposed in our previous work, in this paper, we present an
      improved meshing method to avoid intersections and preserve the topology of the
      molecular Gaussian surface. The new method divides the whole Gaussian surface
      into single valued pieces along each of x, y, z directions by tracing the extreme
      points along the fold curves on the surface. Numerical test results show that the
      surface meshes produced by the new method are manifolds and preserve surface
      topologies. The result surface mesh can also be directly used in surface
      conforming volume mesh generation for FEM type simulation.

PMID- 23117291
TI  - Electronic structures and optical properties of organic dye sensitizer NKX
      derivatives for solar cells: a theoretical approach.
AB  - The photon to current conversion efficiency of dye-sensitized solar cells (DSCs)
      can be significantly affected by dye sensitizers. The design of novel dye
      sensitizers with good performance in DSCs depend on the dye's information about
      electronic structures and optical properties. Here, the geometries, electronic
      structures, as well as the dipole moments and polarizabilities of organic dye
      sensitizers C343 and 20 kinds of NKX derivatives were calculated using density
      functional theory (DFT), and the computations of the time dependent DFT with
      different functionals were performed to explore the electronic absorption
      properties. Based upon the calculated results and the reported experimental work,
      we analyzed the role of different conjugate bridges, chromophores, and electron
      acceptor groups in tuning the geometries, electronic structures, optical
      properties of dye sensitizers, and the effects on the parameters of DSCs were
      also investigated.

PMID- 23117292
TI  - Origin of visible photoluminescence from arrays of vertically arranged Si
      nanopillars decorated with Si-nanocrystals.
AB  - Arrays of vertically aligned Si-nanopillars, with average diameters of 100 nm and
      5 MUm length, have been prepared by wet chemical etching of crystalline silicon
      in a special manner. Samples with smooth- and porous-walled nanopillars have been
      studied. In the case of the latter, Si-nanocrystals, passivated with SiO(x),
      decorating the surface of the nanopillars are identified by the means of TEM and
      FTIR. When excited by UV-blue light, the porous-walled Si-nanopillars are found
      to have a strong broad visible emission band around 1.8 eV with a nearly perfect
      Gaussian shape, MUs luminescence lifetimes, minor emission polarization and a non
      monotonic temperature dependence of luminescence. The Si-nanocrystal surface is
      found to be responsible for the luminescence. The red-shift of the emission
      maximum and the luminescence quenching induced by oxidation in UV-ozone confirm
      this assumption. A model of luminescence involving UV photon absorption by Si
      nanocrystals with subsequent exciton radiative recombination on defect sites in
      SiO(x) covering Si-nanocrystals has been proposed. Possible applications of the
      nanopillar arrays are discussed.

PMID- 23117293
TI  - Curcumin enhances the response of non-Hodgkin's lymphoma cells to ionizing
      radiation through further induction of cell cycle arrest at the G2/M phase and
      inhibition of mTOR phosphorylation.
AB  - It is crucial to enhance tumor radiosensitivity for the purpose of both lowering
      the dose of ionizing radiation (IR) and achieving higher antitumor efficacy. We
      identified curcumin as a radiosensitizer to enhance non-Hodgkin's lymphoma (NHL)
      cell response to IR in vitro and further investigated the mechanism mediating
      this effect. We treated Namalwa, Ramos and Raji cell lines with vehicle,
      curcumin, IR and curcumin-IR. Cell viability and cell cycle distribution were
      determined to ascertain the radiosensitization effect of curcumin. DNA damage
      related proteins, cell cycle regulatory proteins, phosphorylation of mammalian
      target of rapamycin (mTOR) and the nuclear translocation of the downstream
      nuclear factor-kappaB (NF-kappaB) target were examined by western blotting.
      Treatment with curcumin led to decreased viability of all three types of NHL
      cells and had a profound radiosensitization effect. Pre-treatment with curcumin
      at a low concentration of 2 umol/l increased IR-induced G2/M arrest in the cell
      cycle and increased the expression of cyclin-dependent kinase inhibitors, p21cip1
      and p53. However, this effect was blocked when NHL cells were pre-treated with 10
      umol/l of KU55933, a specific inhibitor of ataxia-telangiectasia-mutated (ATM).
      Pre-treatment with curcumin inhibited the phosphorylation of mTOR and the nuclear
      translocation of the downstream NF-kappaB target induced by IR. Curcumin enhanced
      the cell response to IR in NHL mediated through the induction of G2/M phase
      arrest and the inhibition of both a constitutive and IR-induced activation of the
      mTOR-NF-kappaB pathway. This offers great potential for curcumin to be used in
      conjunction with radiotherapy for NHL in order to increase the efficiency of the
      treatment.

PMID- 23117294
TI  - Immune responses against human papillomavirus (HPV) infection and evasion of host
      defense in cervical cancer.
AB  - Human papillomavirus (HPV) is the most important etiological factor for cervical
      cancer. A recent study demonstrated that more than 20 HPV types were thought to
      be oncogenic for uterine cervical cancer. Notably, more than one-half of women
      show cervical HPV infections soon after their sexual debut, and about 90 % of
      such infections are cleared within 3 years. Immunity against HPV might be
      important for elimination of the virus. The innate immune responses involving
      macrophages, natural killer cells, and natural killer T cells may play a role in
      the first line of defense against HPV infection. In the second line of defense,
      adaptive immunity via cytotoxic T lymphocytes (CTLs) targeting HPV16 E2 and E6
      proteins appears to eliminate cells infected with HPV16. However, HPV can evade
      host immune responses. First, HPV does not kill host cells during viral
      replication and therefore neither presents viral antigen nor induces
      inflammation. HPV16 E6 and E7 proteins downregulate the expression of type-1
      interferons (IFNs) in host cells. The lack of co-stimulatory signals by
      inflammatory cytokines including IFNs during antigen recognition may induce
      immune tolerance rather than the appropriate responses. Moreover, HPV16 E5
      protein downregulates the expression of HLA-class 1, and it facilitates evasion
      of CTL attack. These mechanisms of immune evasion may eventually support the
      establishment of persistent HPV infection, leading to the induction of cervical
      cancer. Considering such immunological events, prophylactic HPV16 and 18 vaccine
      appears to be the best way to prevent cervical cancer in women who are immunized
      in adolescence.

PMID- 23117295
TI  - Anti-voltage-gated potassium channel antibody is associated with chronic
      autonomic and sensory neuropathy.

PMID- 23117297
TI  - Bibliography-Editors' selection of current world literature.

PMID- 23117296
TI  - Regulation of GluA1 AMPA receptor through PKC phosphorylation induced by free
      fatty acid derivative HUHS2002.
AB  - The present study investigated the effect of 4-[4-(Z)-hept-1-enyl-phenoxy]
      butyric acid (HUHS2002), a newly synthesized free fatty acid derivative, on alpha
      amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor responses.
      HUHS2002 potentiated currents through GluA1 AMPA receptors expressed in Xenopus
      oocytes in a bell-shaped concentration (1 nM-1 MUM)-dependent manner, the maximum
      reaching nearly 140 % of original amplitude at 100 nM. The potentiation was
      significantly inhibited by GF109203X, an inhibitor of protein kinase C (PKC), but
      not KN-93, an inhibitor of Ca(2+)/calmodulin-dependent protein kinase II
      (CaMKII). HUHS2002 had no potentiating effect on currents through mutant GluA1
      AMPA receptors with replacement of Ser831, a PKC/CaMKII phosphorylation site, by
      Ala. In the in situ PKC assay using rat PC-12 cells, HUHS2002 significantly
      enhanced PKC activity, that is suppressed by GF109203X. Overall, the results of
      the present study show that HUHS2002 potentiates GluA1 AMPA receptor responses by
      activating PKC and phosphorylating the receptors at Ser831, regardless of CaMKII
      activation and phosphorylation.

PMID- 23117298
TI  - Skin tattooing as a novel approach for DNA vaccine delivery.
AB  - Nucleic acid-based vaccination is a topic of growing interest, especially plasmid
      DNA (pDNA) encoding immunologically important antigens. After the engineered pDNA
      is administered to the vaccines, it is transcribed and translated into immunogen
      proteins that can elicit responses from the immune system. Many ways of
      delivering DNA vaccines have been investigated; however each delivery route has
      its own advantages and pitfalls. Skin tattooing is a novel technique that is
      safe, cost-effective, and convenient. In addition, the punctures inflicted by the
      needle could also serve as a potent adjuvant. Here, we a) demonstrate the
      intradermal delivery of plasmid DNA encoding enhanced green fluorescent protein
      (pCX-EGFP) in a mouse model using a tattooing device and b) confirm the effective
      expression of EGFP in the skin cells using confocal microscopy.

PMID- 23117299
TI  - N-heterocyclic carbene-catalyzed [4 + 2] cycloaddition of ketenes and 3
      aroylcoumarins: highly enantioselective synthesis of dihydrocoumarin-fused
      dihydropyranones.
AB  - The N-heterocyclic carbene-catalyzed [4 + 2] cyclization of ketenes and 3
      aroylcoumarins has been developed to give the corresponding dihydrocoumarin-fused
      multisubstituted dihydropyranones in high yield with good diastereoselectivity
      and high enantioselectivity.

PMID- 23117301
TI  - Cone-beam computed tomography images of phantoms with simulating trabecular bone
      structure fabricated using micro-stereolithography.
AB  - OBJECTIVE: Phantoms with simulating mandibular trabecular bone structure
      fabricated using micro-stereolithography were applied for a quantitative
      evaluation of cone-beam computed tomography (CT) images. MATERIALS AND METHODS:
      Phantoms with a three-dimensional lattice, in which a square pillar was set at
      0.10, 0.20, 0.30 and 0.40 mm at the edge, spaced at 0.60 mm, were made of an
      acrylic resin using micro-stereolithography. Cone-beam CT with a 0.1 mm-cubic
      voxel was then performed, and a plot profile of voxel values was analyzed.
      RESULTS: The plot profiles of seven peaks corresponding to pillars in phantoms
      with 0.20, 0.30 and 0.40 mm-pillars were visually observed in cone-beam CT
      images. However, peaks of corresponding pillars in the 0.10 mm-pillar phantom
      could not be distinguished. The differences between average measured and designed
      distance were very small. CONCLUSION: Cone-beam CT images of phantoms with 0.20,
      0.30 and 0.40 mm-pillars fabricated using microstereolithography were obtained.

PMID- 23117300
TI  - The deletion of exons 3-5 of BRCA1 is the first founder rearrangement identified
      in breast and/or ovarian cancer Spanish families.
AB  - We recently described a novel g.8097_22733del14637 deletion encompassing exons 3
      5 in BRCA1 gene. This rearrangement was detected in 3 of 15 (20 %) breast and/or
      ovarian cancer families of Eastern Spain. This finding made us suspect that the
      newly identified deletion could be a founder mutation. To confirm this hypothesis
      we studied 18 subjects belonging to the three families under study, 11 deletion
      carriers and 7 non-carriers. We performed a haplotype analysis using two BRCA1
      intragenic microsatellite markers and two markers surrounding the BRCA1 locus.
      The segregation analysis showed one common particular haplotype established by
      D17S1325, D17S1323, D17S855 and D17S1320 markers detected in the deletion
      carriers but absent in the non-carriers. Our study sustain that the deletion of
      exons 3-5 of BRCA1, g.8097_22733del14637, identified in families of southeastern
      of the Valencian Community is the first founder rearrangement until now reported
      in Spanish population, confirming the hypothesis that this mutation could have
      Iberian ancestry.

PMID- 23117302
TI  - Effects of androgens on cultured cells derived from canine anterior cruciate
      ligament.
AB  - Anterior cruciate ligament (ACL) fibroblasts obtained from beagle dogs were
      cultured in basal medium containing different concentrations of 1 to 10(-3) uM
      5alpha-dihydrotestosterone (DHT) and in basal medium itself as a control. It was
      demonstrated that DHT promoted cell proliferation activity, expression of
      androgen receptor, and collagen synthesis in ACL fibroblasts as compared with
      control. These results suggest that sex hormones are involved in the sex
      difference seen in ACL rupture of dogs.

PMID- 23117303
TI  - Distribution of myofiber types in the crural musculature of sheep.
AB  - In domestic animals, the legs function in both postural maintenance and
      propulsion. The crural muscles participate in actions of the tarsal and toe
      joints. Mammalian skeletal muscles consist of myofibers, which are
      histochemically classified into three myofiber types, slow-twitch/oxidative (SO)
      or type I, fast-twitch/oxidative/glycolytic (FOG) or type IIA, and fast
      twitch/glycolytic (FG) or type IIB myofibers. The histochemical characteristics
      of myofiber types reflect an aspect of function that myofibers possess. In the
      present study, we investigated the composition and average diameter of myofiber
      types of each muscle in crus of sheep and determined their roles in the movement
      of tarsal and toe joints. The tibialis cranialis muscle was a flat unipennate
      muscle and not capable to generate a large tension; however, it could function
      primarily in posture maintenance and play a cooperative role in adjusting
      standing posture. The flexor hallucis longus and flexor digitorum superficialis
      muscles were the major muscles that contributed to posture maintenance in leg
      musculature. These muscles were capable to generate a large tension and
      participate primarily in standing posture maintenance. The composition and
      diameter of myofiber types in ovine crural musculature reflected the role of each
      muscle in posture maintenance and locomotion.

PMID- 23117304
TI  - Innervation of TRPV1-, PGP-, and CGRP-immunoreactive nerve fibers in the
      subepithelial layer of a whole mount preparation of the rat cornea.
AB  - The pattern of innervation of capsaicin receptor, TRPV1-(transient receptor
      protein vanilloid 1), PGP 9.5-(protein gene product, a marker of peripheral nerve
      fibers)-, and CGRP (calcitonin gene-related peptide)-immunoreactive (IR) nerve
      fibers was examined by immunohistological staining of whole mount preparations of
      the adult rat cornea. The outer corneoscleral limbus toward the central cornea in
      the subepithelial (stromal) layer was richly innervated by a meshwork of PGP- and
      CGRP-IR nerve fibers. Sparse innervation was observed in the central cornea,
      presumably owing to insufficient staining. Dense innervation of TRPV1-IR nerve
      fibers were demonstrated in addition to innervation of PGP- and CGRP-IR nerve
      fibers, running from the corneoscleral margin to the central cornea. Although the
      density of TRPV1-IR nerve fibers appeared to gradually diminish, immunostaining
      of TRPV1-IR nerve fibers was not as clear as that of PGP- and CGRP-IR nerve
      fibers. The TRPV1-IR nerve fibers appeared to be thinner than the PGP- and CGRP
      IR nerve fibers. The TRPV1-IR leash fibers were observed in the basal epithelial
      layer, presumably ensuring effective corneal reflex, response to noxious stimuli,
      and repair of cornea injury.

PMID- 23117305
TI  - Morpho-functional relationship between muscular architecture and proportion of
      myofiber types in ovine antebrachial musculature.
AB  - The antebrachium of domestic animals supports the trunk against gravity and
      generates propulsive force. The antigravity action of antebrachium is attributed
      to the contraction of flexor muscles of the carpal and digital joints. Mammalian
      skeletal muscles consist of myofibers, which are histochemically classified into
      type I, type IIA, and type IIB myofibers, of which composition reflects the
      proportional involvement of the muscle in varying function, such as posture
      maintenance and locomotion. The physiological cross-sectional area (PCSA), which
      are calculated from muscle volume, myofiber length, and pennation angle, reflects
      the maximum force of muscle. In the present study, we evaluated the PCSA of
      myofiber types in the antebrachial musculature and determined the magnitude of
      contribution from individual muscles toward varying actions of carpal and digital
      joints. The extensor carpi ulnaris and flexor digitorum superficialis muscles
      possessed a large proportional PCSA of type I myofibers, indicating the role for
      these muscles in maintaining a standing posture. The additional force required
      for walking/running was primarily provided by the flexor digitorum profundus
      caput humerale and extensor carpi radialis muscles. The proportional PCSA of
      myofiber types reflected the force generated for varying muscular function and
      provided insights into the dynamics of carpal and digital joints.

PMID- 23117306
TI  - Practice on an augmented reality/haptic simulator and library of virtual brains
      improves residents' ability to perform a ventriculostomy.
AB  - INTRODUCTION: Ventriculostomy is a neurosurgical procedure for providing
      therapeutic cerebrospinal fluid drainage. Complications may arise during repeated
      attempts at placing the catheter in the ventricle. We studied the impact of
      simulation-based practice with a library of virtual brains on neurosurgery
      residents' performance in simulated and live surgical ventriculostomies. METHODS:
      Using computed tomographic scans of actual patients, we developed a library of 15
      virtual brains for the ImmersiveTouch system, a head- and hand-tracked augmented
      reality and haptic simulator. The virtual brains represent a range of anatomies
      including normal, shifted, and compressed ventricles. Neurosurgery residents
      participated in individual simulator practice on the library of brains including
      visualizing the 3-dimensional location of the catheter within the brain
      immediately after each insertion. Performance of participants on novel brains in
      the simulator and during actual surgery before and after intervention was
      analyzed using generalized linear mixed models. RESULTS: Simulator cannulation
      success rates increased after intervention, and live procedure outcomes showed
      improvement in the rate of successful cannulation on the first pass. However, the
      incidence of deeper, contralateral (simulator) and third-ventricle (live)
      placements increased after intervention. Residents reported that simulations were
      realistic and helpful in improving procedural skills such as aiming the probe,
      sensing the pressure change when entering the ventricle, and estimating how far
      the catheter should be advanced within the ventricle. CONCLUSIONS: Simulator
      practice with a library of virtual brains representing a range of anatomies and
      difficulty levels may improve performance, potentially decreasing complications
      due to inexpert technique.

PMID- 23117308
TI  - Sequential use of bare-metal stents and drug-coated balloons to treat coronary
      artery stenosis.
AB  - INTRODUCTION: Drug-coated balloons (DCBs) are increasingly used in percutaneous
      coronary intervention (PCI). The sequential use of DCB and bare-metal stent (BMS)
      represents a novel approach and results of pilot studies have been encouraging.
      The aim of this study was to assess long-term outcomes of patients who received
      treatment with DCB and BMS and additionally study whether the order (BMS or DCB
      first) affected outcomes. METHODS: This is a single-center, non-randomized,
      prospective study of patients who underwent PCI between July 2009 and July 2011.
      Two groups were defined: DCB followed by BMS (DCB->BMS) or BMS followed by DCB
      (BMS->DCB). Our primary outcome was target lesion revascularization (TLR) at 7
      months. RESULTS: A total of 128 patients (173 lesions) with a mean age of 67
      years were included. The BMS->DCB group consisted of 53 patients (78 lesions) and
      the DCB->BMS group consisted of 75 patients (95 lesions). The mean follow-up was
      7.4 months. The TLR rate was 4/76 (5%) in the BMS->DCB group and 3/90 (3%) in the
      DCB->BMS group (P=.83). CONCLUSION: Our study demonstrates good results of
      sequential BMS and DCB use in an all-comers population. If confirmed by larger
      studies, this could be a valuable approach in patients with contraindications to
      drug-eluting stent implantation.

PMID- 23117307
TI  - Response of chronic cough to acid-suppressive therapy in patients with
      gastroesophageal reflux disease.
AB  - BACKGROUND: Epidemiologic and physiologic studies suggest an association between
      gastroesophageal reflux disease (GERD) and chronic cough. However, the benefit of
      antireflux therapy for chronic cough remains unclear, with most relevant trials
      reporting negative findings. This systematic review aimed to reevaluate the
      response of chronic cough to antireflux therapy in trials that allowed us to
      distinguish patients with or without objective evidence of GERD. METHODS: PubMed
      and Embase systematic searches identified clinical trials reporting cough
      response to antireflux therapy. Datasets were derived from trials that used pH
      metry to characterize patients with chronic cough. RESULTS: Nine randomized
      controlled trials of varied design that treated patients with acid suppression
      were identified (eight used proton pump inhibitors [PPIs], one used ranitidine).
      Datasets from two crossover studies showed that PPIs significantly improved cough
      relative to placebo, albeit only in the arm receiving placebo fi rst. Therapeutic
      gain in seven datasets was greater in patients with pathologic esophageal acid
      exposure (range, 12.5%-35.8%) than in those without (range, 0.0%-8.6%), with no
      overlap between groups. CONCLUSIONS: A therapeutic benefit for acid-suppressive
      therapy in patients with chronic cough cannot be dismissed. However, evidence
      suggests that rigorous patient selection is necessary to identify patient
      populations likely to be responsive, using physiologically timed cough events
      during reflux testing, minimal patient exclusion because of presumptive
      alternative diagnoses, and appropriate power to detect a modest therapeutic gain.
      Only then can we hope to resolve this vexing clinical management problem.

PMID- 23117309
TI  - Serial Evaluation of Vascular Response After Implantation of a New Sirolimus
      Eluting Stent With Bioabsorbable Polymer (MISTENT): an optical coherence
      tomography and histopathological study.
AB  - BACKGROUND: Novel vascular scaffolds aim at equipoise between safety and
      efficacy. Intravascular optical coherence tomography (OCT) allows in-vivo serial
      assessment of stent-vessel interactions with high resolution and frequent
      sampling and may complement histology assessment. We investigated the vascular
      response to a novel absorbable coating sirolimus-eluting stent (AC-SES) by means
      of serial OCT and histology evaluation in a porcine model. METHODS: One AC-SES
      and one bare-metal stent (BMS) were implanted in separate coronary arteries of
      three Yucatan mini-swine. Serial OCT was performed post procedure and at 3-, 28-,
      90-, and 180-day follow-up. Normalized optical density (NOD) was used for the
      assessment of tissue response over time. Histological evaluation was performed at
      day 180. RESULTS: A total of 6408 stent struts were analyzed. OCT revealed 100%
      of struts covered at 28 days, and a significant difference in NOD from 3 to 28
      days (0.64 +/- 0.07 vs 0.71 +/- 0.05, respectively; P<.001) in the AC-SES group.
      Neointimal thickness was 0.14 +/- 0.08 mm, 0.17 +/- 0.11 mm, and 0.16 +/- 0.09 mm
      in the AC-SES group and 0.18 +/- 0.10 mm, 0.14 +/- 0.09 mm, and 0.10 +/- 0.08 mm
      in the BMS group, while rates of uncovered struts were 0%, 0%, and 3.1% and 1.4%,
      7.8%, and 21.5%, respectively, at 28, 90, and 180 days. Minimal inflammation and
      a mature endothelialization were demonstrated in both groups by histology.
      CONCLUSION: OCT serial assessment of vascular response suggested NIH maturation
      28 days following AC-SES implantation in pigs. These findings, coupled with
      histological demonstration of low inflammation scores and complete endothelial
      coverage as measured at 180 days, suggest a satisfactory healing response to AC
      SES.

PMID- 23117311
TI  - Repeat drug-eluting stent implantation for in-stent restenosis: first- or second
      generation stent.
AB  - OBJECTIVE: To investigate the efficacy and safety of a second-generation drug
      eluting stent (DES) for in-stent restenosis (ISR) after first-generation DES
      implantation. BACKGROUND: The everolimus-eluting stent is a second-generation DES
      that is very effective for de novo coronary lesions. METHODS: The subjects were
      145 consecutive patients who underwent re-stenting, including 93 given a first
      generation DES and 52 given a second-generation DES. The two groups were followed
      up for 37.8 +/- 16.7 months and 13.8 +/- 2.1 months, respectively. The primary
      endpoint was in-stent late luminal loss at 8-month angiographic follow-up.
      RESULTS: Baseline clinical and angiographic parameters were similar in the 2
      groups. Follow-up angiography showed that late luminal loss (0.26 +/- 0.31 mm vs
      0.58 +/- 0.67 mm; P=.01), the binary restenosis rate (2.6% vs 16.7%; P=.03), and
      the target lesion revascularization (TLR) rate (1.9% vs 11.8%; log-rank = 0.04)
      were smaller in the second-generation group than in the first-generation group.
      There was no definite stent thrombosis in either group. During follow-up, there
      were no significant between-group differences of major adverse cardiac events
      without TLR, myocardial infarction, death, and death + myocardial infarction.
      Multivariate analysis demonstrated that using a first-generation DES was the only
      independent predictor of TLR after 1 year (odds ratio, 2.78; 95% confidence
      interval, 1.22-5.43; P=.03). CONCLUSION: When ISR occurs after DES implantation,
      treatment with a second-generation DES reduces late luminal loss, binary
      restenosis, and TLR after 1 year compared with a first-generation DES.

PMID- 23117310
TI  - Serial optical coherence tomography-based observation of strut coverage on drug
      eluting stent crossing side-branch vessels.
AB  - BACKGROUND: Serial changes in strut coverage of drug-eluting stents (DESs), which
      are placed across side-branch vessels, remain unclear. METHODS: The changes in
      strut coverage of DESs crossing side-branch vessels (size >=2.0 mm) were serially
      evaluated by optical coherence tomography (OCT) in 30 patients at 9 months and 2
      years after the index DES implantation. DESs were paclitaxel-eluting stents
      (PESs), sirolimus-eluting stents (SESs), and zotarolimus-eluting stents (ZESs),
      each in 10 patients. Measured neointimal hyperplasia (NIH) thickness of 0 MUm on
      OCT was defined as an uncovered strut. RESULTS: The percentage of uncovered side
      branch struts significantly decreased from 55.7 +/- 39.9% to 36.6 +/- 32.0%
      (P<.0001) on serial follow-up: PES, 93.4 +/- 10.5% to 67.6 +/- 24.2%, P=.018;
      SES, 47.5 +/- 34.4% to 29.6 +/- 24.1%, P=.036; and ZES, 26.2 +/- 34.8% to 12.4 +/
      19.0%, P=.028. Among covered side-branch struts, the overall percentage of
      struts with NIH thickness more than 30 MUm significantly increased from 36.3 +/-
      37.4% to 51.0 +/- 36.0% (P<.0001). However, compared to other DES types, a
      significant increase in relatively thin NIH (0 to 30 MUm) was observed in PESs
      (1.6 +/- 3.4% to 17.4 +/- 16.0%; P=.018). CONCLUSION: Serial follow-up OCT
      examination showed a significant decrease in the percentage of uncovered side
      branch struts, and the coverage pattern differed with DES type.

PMID- 23117312
TI  - Percutaneous closure of medium and large PDAs using amplatzer duct occluder (ADO)
      I and II in infants: safety and efficacy.
AB  - BACKGROUND: The use of the Amplatzer duct occluder (ADO; AGA Medical Corporation)
      is well established and reported in children and adults, but there are only
      occasional reports on use in symptomatic infants. METHODS AND RESULTS: Between
      March 2009 and January 2011, a group of 47 infants less than 2 years of age with
      symptomatic patent ductus arteriosus (PDA) was treated using ADO I and II
      devices. Patients were divided into infants less than 1 year old (group A; n =
      28/47; 59.6%) and children between 1 and 2 years old (group B; n = 19/47; 40.4%).
      Physical examinations and echocardiograms were performed before the procedure and
      at follow-up (3, 6, and 12 months). Mean age was 5.3 +/- 2.3 months for group A
      and 12.6 +/- 1.7 months for group B. Mean weight at closure was 4.8 +/- 1.9 kg
      for group A and 7.3 +/- 2.1 kg for group B. ADO I was deployed in 19/28 of group
      A (67.9%) and 16/19 of group B (84.2%). ADO II was used in 9/28 of group A
      (32.1%) and 3/19 of group B (15.8%). No residual shunt at the end of the
      procedure was detected by angiography in any of the cases closed with ADO I and
      only 3/12 (25%) closed with ADO II showed a minimal residual flow. No mortality
      or major complications occurred. Six months after closure, weight gain, control
      of respiratory infections, and regression of left ventricular dilatation with
      improved systolic function were observed. CONCLUSIONS: Percutaneous closure of
      moderate to large PDAs using ADO I and II devices in infants and children younger
      than 2 years of age is safe and effective.

PMID- 23117313
TI  - Intra-aortic counterpulsation for hemodynamic support in patients with acute
      ischemic versus non-ischemic heart failure.
AB  - BACKGROUND: Intra-aortic counterpulsation (IABP) is frequently applied to provide
      hemodynamic support in patients with refractory cardiogenic shock (CS) of
      ischemic and non-ischemic cause. However, clinical data comparing outcomes are
      lacking for both indications. The purpose of this analysis was to evaluate
      outcome and safety of IABP support in patients with ischemic and non-ischemic CS
      and to identify predictors of early mortality in this severely ill patient
      population. METHODS AND RESULTS: For the period between 1998 to 2010, data from
      489 consecutive patients (age, 67.2 +/- 12.2 years; 65.9% male) who had received
      IABP support for CS at the University Heart Center Jena were retrospectively
      analyzed. The primary endpoint was overall mortality at 7 and 30 days. Secondary
      endpoints included the incidence of vascular and neurologic complications as well
      as long-term survival. Follow-up data on current health status of the patients
      were acquired either from health insurance records or based on patient and
      physician interviews. After data compilation, patients were assigned to one of
      the following subgroups: ST-elevation myocardial infarction (STEMI; n = 368;
      75.3%), non-STEMI (n = 75; 15.3%) and congestive heart failure (CHF; n = 46;
      9.4%). Of the 489 patients enrolled, 422 (86.4%) were successfully weaned from
      IABP support. However, a significantly lower proportion of patients were weaned
      successfully in the STEMI group (n = 310; 84.1%) compared to the other two groups
      (non-STEMI: n = 70, 92.4%; CHF: n = 45, 97.8%; P=.041). Overall mortality at 30
      days was 36.4% (n = 178) and was not significantly different between the
      subgroups. Significant predictors of 30-day mortality included age >70 years
      (odds ratio [OR], 16.81; confidence interval [CI], 1.241-227.54), ejection
      fraction <40% (OR, 36.33; CI, 2.93-451.05) and mechanical ventilation (OR, 12.42;
      CI, 1.21-127.17). Long-term follow-up was 803 +/- 1061 days (range, 0-1380 days),
      with a long-term survival rate of 38.3%. CONCLUSION: IABP represents a safe
      technology for hemodynamic support and is associated with low complication rates.
      Parameters relating to early mortality include age >70 years, respiratory failure
      requiring mechanical ventilation, and left ventricular function <40%, which
      represent an additional risk of death. However, the etiology of CS had no effect
      on mortality in this analysis. This observation should encourage physicians to
      apply IABP for hemodynamic support in patients with nonischemic left ventricular
      failure.

PMID- 23117314
TI  - Comparison of surgical pericardial drainage with percutaneous catheter drainage
      for pericardial effusion.
AB  - OBJECTIVE: We sought to investigate the outcomes for different treatments of
      pericardial effusions. BACKGROUND: The optimal initial management for symptomatic
      pericardial effusions remains controversial. METHODS: We performed a 3-year
      retrospective, single-institution study comparing open surgical drainage to
      percutaneous pericardiocentesis for symptomatic pericardial effusions. RESULTS:
      Between 2007 and 2009, a total of 193 patients underwent an initial drainage
      procedure for a pericardial effusion (n = 121 [62.7%] pericardiocentesis; n = 72
      [37.3%] open surgical drainage). Compared to those treated with
      pericardiocentesis, treatment with open surgical drainage was associated with a
      higher complication rate (4.9% vs 26.4%; P<.0001; odds ratio [OR], 6.9; 95%
      confidence interval [CI], 2.6-18.2). Treatment with pericardiocentesis was
      associated with a higher rate of repeat procedures to drain a recurrent effusion
      compared to open surgical drainage (28.9% vs 2.8%; P<.0001; OR, 14.2; 95% CI, 3.3
      61.3). Thirty-day mortality (19.8% surgical group vs 18.1% pericardiocentesis
      group; P=.8) and long-term survival (P=.4) did not differ between the groups.
      CONCLUSION: There is no significant difference in overall mortality between open
      surgical drainage and percutaneous pericardiocentesis for symptomatic pericardial
      effusions. There may be more procedural complications following surgical drainage
      of a pericardial effusion, and a greater need for repeat procedures if the
      effusion is drained using pericardiocentesis.

PMID- 23117315
TI  - The accuracy of three-dimensional echocardiography with multiplanar reformatting
      in the assessment of the aortic valve annulus prior to percutaneous balloon
      aortic valvuloplasty in congenital heart disease.
AB  - OBJECTIVE: To review the use of three-dimensional echocardiography (3DE) with
      multiplanar reformatting (MPR) in children with congenital aortic stensosis
      undergoing percutaneous balloon aortic valvuloplasty to assess its accuracy in
      measuring the aortic valve annulus and any influence it may have on balloon
      sizing. METHODS: All percutaneous aortic balloon valvuloplasties performed from
      01/01/2009 to 01/09/2011 were included in the study. All imaging performed for
      the procedure to determine the size of the aortic valve annulus and aid in
      balloon sizing was reviewed. The maximum diameter of the aortic valve annulus
      using two-dimensional echocardiography (2DE), 3DE with MPR, and angiography was
      recorded. The balloon size used in the procedure was recorded and the balloon to
      annulus ratio was calculated. RESULTS: A total of 27 procedures were included in
      the study. Age varied from 1 day to 156 months (mean age, 53 months) and weight
      from 2.8-58 kg (mean weight, 18.6 kg). Fourteen patients had 3DE with MPR
      available for analysis. The 3DE with MPR measurement (13.36 +/- 5.4 mm) was not
      different from angiography (13.54 +/- 6.4 mm; P=.803).The 2DE measurement was
      significantly different from angiography (11.72 +/- 5 mm; P<.005). The balloon to
      annulus ratio based on angiographic measurements did not differ significantly
      between the patients with 3DE MPR and those without (0.94 +/- 0.095 vs 0.91 +/-
      0.1; P=.468). CONCLUSION: 3DE with MPR allows a more accurate assessment of the
      aortic valve annulus compared to 2DE, which may reduce the tendency to undersize
      balloon choice. 3DE with MPR did not significantly affect our balloon choice,
      which was largely based on angiographic measurements.

PMID- 23117316
TI  - Learning curve in transradial cardiac catheterization: procedure-related
      parameters stratified by operators' transradial volume.
AB  - OBJECTIVE: To determine whether radial artery access is associated with a
      reduction in fluoroscopy time, procedure time, and other procedural variables
      over a 27-month period during which the radial artery approach was incorporated
      in a single academic Medical Center. BACKGROUND: Although previous studies have
      demonstrated a relationship between increased volume and decreased procedural
      time, no studies have looked at the integration of radial access over time.
      METHODS: Data were collected from consecutive patients who presented to the
      Vanderbilt University Medical Center cardiac catheterization laboratory from
      January 1, 2009 to April 1, 2011. Patients who underwent radial access diagnostic
      catheterization with and without percutaneous coronary intervention were included
      in this study. A total of 1112 diagnostic cardiac catheterizations through the
      radial access site were analyzed. High-volume, intermediate-volume, and low
      volume operators were grouped based on the percentage of procedures performed
      through a radial approach. RESULTS: From 2009 to 2011, there was a significant
      decrease in fluoroscopy time in all operator groups for diagnostic
      catheterization (P=.035). The high-volume operator group had 1.88 and 3.66 minute
      reductions in fluoroscopy time compared to the intermediate- and low-volume
      operator groups, respectively (both P<.001). Likewise, the intermediate-volume
      operator group had a 1.77 minute improvement compared to the low-volume operator
      group, but this did not reach statistical significance (P=.102). The improvement
      in fluoroscopy time and other procedure-related parameters was seen after
      approximately 25 cases with further improvement after 75 cases. CONCLUSIONS: The
      incorporation of the radial access approach in the cardiac catheterization
      laboratory led to a decrease in fluoroscopy time for each operator and operator
      group over the last 3 years. Our data demonstrated that higher-volume radial
      operators have better procedure, room, and fluoroscopy times when compared to
      intermediate- and low-volume operators. However, lower-volume operators have a
      reduction in procedure-related parameters with increased radial cases. Number of
      procedures needed to become sufficient was demonstrated in the current study.

PMID- 23117317
TI  - Prone position coronary angiography due to intractable back pain: another merit
      of transradial approach compared to transfemoral approach.
AB  - We report a case of prone position coronary angiography due to intractable back
      pain via left transradial approach. When a patient cannot lie down in a supine
      position, prone position coronary angiography can be performed alternatively.
      This may be another merit of transradial approach compared to transfemoral
      approach on the evaluation of patients with suspected coronary artery disease.

PMID- 23117318
TI  - Off-label closure during CLOSURE study.
AB  - BACKGROUND: The role of percutaneous closure of patent foramen ovale (PFO) in
      patients with cryptogenic stroke or transient ischemic attack remains
      controversial. Registry data have suggested considerable benefit of closure over
      medical therapy, but the prospective, randomized CLOSURE I trial found no benefit
      for device closure. METHODS: We compared patients enrolled into CLOSURE I to off
      label closures performed during the study recruitment period at a single large
      institution and prospectively enrolled into an institutional registry of PFO
      closure. We also compared CLOSURE I patients at our institution to the reported
      characteristics of the entire study to ensure generalizability. RESULTS: Between
      11/3/2003 and 4/16/2007, there were 100 off-label closures and 33 patients
      randomized into CLOSURE I. Compared with off-label closure, patients in CLOSURE I
      were younger (41.6 +/- 10.1 years vs 50.0 +/- 14.0 years; P<.001) and had fewer
      cardiovascular risks including hypertension (12% vs 36%; P=.009), hyperlipidemia
      (24% vs 53%; P=.008), and coronary disease (3% vs 44%; P<.001). Degree of right
      to-left shunting was considerably higher in off-label closures (28%, 14%, and 58%
      vs 45%, 30%, and 25% for mild, moderate, and severe, respectively; P=.026).
      CONCLUSION: Off-label closures outnumbered patient recruitment into CLOSURE 3:1
      at our institution during study recruitment. Certain demographic differences were
      expected (age over 60 was an exclusion for CLOSURE I), but vascular risks were
      considerably greater in the off-label group and may be important mechanistically.
      Large shunts were considerably more common in off-label patients, suggesting that
      higher-risk patients may have been preferentially closed off-label. These results
      suggest that the results of CLOSURE I may not apply to all patients with initial
      cryptogenic stroke.

PMID- 23117319
TI  - Intervention in the occluded vein graft: with high risk can come great reward:
      review of techniques with case examples.
AB  - Total occlusion of a saphenous vein graft (SVG) can present as abrupt thrombotic
      occlusion in an atherosclerotic graft with resultant acute cardiac events or
      chronic total occlusion (CTO) with resultant angina symptoms. The risks of
      percutaneous coronary intervention (PCI) within an occluded graft include not
      only periprocedural myocardial infarction (MI), but also the risks that come part
      and parcel with any CTO intervention which include an increased probability of
      procedural failure, vessel perforation, dissection, high radiation, and contrast
      exposure, and the potential for worse outcomes. PCI of a chronically occluded
      graft remains a class III indication in current PCI guidelines because of the
      increased procedural risk and modest clinical data supporting improved outcomes.
      Acute-type occlusions, with bulky and thrombotic obstruction, while not
      specifically addressed in the guidelines, are also fraught with somewhat similar
      risks. In this review, we describe four case scenarios with occluded SVG and
      discuss challenges and techniques and available evidence that support these
      interventions.

PMID- 23117320
TI  - Thrombus aspiration with microcatheter for distal embolization during primary
      angioplasty for acute myocardial infarction: technical notes.
AB  - We describe a new technique for removing distal emboli that became visible on
      angiography during percutaneous coronary intervention for acute myocardial
      infarction. Three patients presented with distal embolization as a filling defect
      with an abrupt cut-off in 1 of the peripheral coronary vessels of the infarct
      related coronary artery. After a failed attempt to retrieve the thrombus with a
      conventional aspiration catheter, the thrombus was trapped at the tip of a
      microcatheter by aspiration and was successfully retrieved. This procedure can
      achieve prompt restoration of distal coronary flow.

PMID- 23117321
TI  - Anomalous origin of the right coronary artery with intramural aortic course
      causing exercise-induced cardiac arrest.

PMID- 23117322
TI  - Direct aspiration of large thrombi in acute myocardial infarction using a
      standard 6 Fr guide catheter via the transradial approach.
AB  - A large thrombus load on the culprit coronary artery of patients with acute
      myocardial infarction (MI) is associated with increased procedural complications
      and adverse coronary events following angioplasty. This case series describes
      effective removal of large, occlusive thrombi in acute MI via direct aspiration
      using a standard 6 Fr guide catheter, following failed conventional catheter
      aspiration. This procedure is a simple and rapid alternative for challenging
      thrombi-containing coronary lesions when current thrombectomy catheters fail.

PMID- 23117323
TI  - Percutaneous catheter-based left atrial appendage ligation and management of
      periprocedural left atrial appendage perforation with the LARIAT suture delivery
      system.
AB  - We report an 88-year-old male with coronary artery disease, previously placed
      left main coronary artery drug-eluting stent, and atrial fibrillation unable to
      tolerate anticoagulation with warfarin in addition to dual antiplatelet therapy
      who underwent percutaneous catheter-based ligation of the left atrial appendage.
      During the procedure, left atrial appendage perforation occurred with resultant
      pericardial effusion. The novel LARIAT suture delivery system (SentreHEART)
      allowed immediate and definitive management of this complication and effective
      ligation of the left atrial appendage. Prospective studies are needed to
      determine whether this is a safe and effective method for thromboembolism
      prophylaxis in patients with atrial fibrillation, but its novel design
      incorporates an immediate resolution to the most-feared complication of catheter
      based left atrial appendage manipulation while effectively excluding the left
      atrial appendage via suture ligation.

PMID- 23117324
TI  - Intracardiac aspiration for life-threatening air embolism during cardiac
      catheterization in tetralogy of Fallot: an aborted sudden death.
AB  - Accidental introduction of air into veins can occur during a variety of surgical
      operations or diagnostic procedures. High mortality rate results without early
      diagnosis and appropriate treatment. This is due to "air lock" at the right
      ventricular outflow tract, compromising the left ventricular filling. We describe
      a 2-year-old male with Tetralogy of Fallot who developed air embolism due to
      unexpected rupture of Swan-Gang catheter during a cardiac catheterization study,
      which was managed successfully by intracardiac aspiration.

PMID- 23117325
TI  - Dislocation of an infected and abandoned pacemaker lead.
AB  - We present a case of pacemaker lead dislodgment in an 83-year-old patient with a
      pacemaker infection. Initially, the generator and the proximal part of the leads
      were removed, and the remaining leads were severed and abandoned. Twenty-five
      days later, dislodgment of both abandoned leads and systemic infection were
      documented. The leads were then surgically removed without further complications.

PMID- 23117326
TI  - Relationship between myocardial bridges and arrhythmic complications.
AB  - Myocardial bridge (MB) is defined as compression of coronary artery during
      systole while it is normal in diastole. In angiographic series, the prevalence of
      this anomaly was reported between 0.5% and 2.5%. It is occasionally seen in the
      middle segment of the left anterior descending coronary artery. Although MB is
      considered to be a benign anomaly, the association of MB with ischemia, systolic
      dysfunction, conduction abnormality, arrhythmias, and sudden cardiac death were
      reported. Herein, we report 3 cases of MB that were diagnosed with coronary
      angiography and were associated with arrhythmic complications. In 2 patients,
      complete atrioventricular block was present, and another patient was diagnosed
      with sick sinus syndrome with the help of an electrophysiological study. All
      patients underwent permanent cardiac pacemaker implantation.

PMID- 23117327
TI  - Coronary to bronchial artery fistula: are we treating it right?
AB  - Fistulas between coronary artery and bronchial artery may be present from birth,
      with few hemodynamic consequences, and may remain closed due to similarity of the
      filling pressures at these 2 sites. They can also be secondary to pulmonary
      artery occlusive disease or chronic pulmonary inflammation. These pulmonary
      changes may cause a dilation of the fistula and make it functional, causing
      angina pectoris by coronary steal syndrome, which is the most common symptom. The
      presentation may also be composed of episodes of hemoptysis, heart failure, and
      infective endocarditis. However, most patients remain asymptomatic. The ones that
      need treatment may not have a good response to the medical management, requiring
      an intervention. This can be done using embolization coils, stents grafts, and
      performing surgical ligation of the fistulas.

PMID- 23117328
TI  - Catheter-induced bilateral coronary ostium dissection in a patient with long-term
      steroid therapy.
AB  - Catheter-induced coronary dissection is a very rare and serious complication. We
      report a case of a 44-year-old man with catheter-induced bilateral coronary
      dissection that occurred during diagnostic coronary angiography for angina. The
      coronary dissection was successfully treated by stenting at the left main trunk,
      the left anterior descending artery, and the right coronary ostium. The patient
      had been maintained on long-term steroid therapy for nephrotic syndrome. The
      effect of long-term steroid therapy on bilateral coronary dissection is worthy of
      discussion.

PMID- 23117329
TI  - Bright-light effects on cognitive performance in elderly persons working
      simulated night shifts: psychological well-being as a mediator?
AB  - PURPOSE: The present study examined whether the relationship between light
      exposure and cognitive functioning is mediated by psychological well-being in
      elderly persons working night shifts. The role of psychological well-being has
      been neglected so far in the relationship between bright light and cognitive
      performance. Sleepiness and mood were applied as indicators of psychological well
      being. Cognitive functioning was examined in terms of concentration, working
      memory, and divided attention. METHODS: A total of thirty-two test persons worked
      in three consecutive simulated night shifts, 16 under bright light (3,000 lux)
      and 16 under room light (300 lux). Concentration, working memory, and divided
      attention were measured by computerised tasks. The hypothesised mediators were
      recorded by questionnaires. RESULTS: Mediation analyses were conducted for
      estimating direct, total, and indirect effects in simple mediation models.
      Results indicate that sleepiness and mood did not function as mediators in the
      prediction of concentration, working memory, and/or divided attention by light
      exposure. CONCLUSIONS: Sleepiness led to an underestimation of the positive
      bright-light effect on concentration performance. Mood showed only a random
      effect due to the positive bright-light effect on working memory. Sleepiness and
      mood could completely be excluded as mediators in the relationship between light
      exposure and cognitive functioning. This study underlines that psychological well
      being of elderly persons is not a critical component in the treatment of bright
      light on cognitive performance in the night shift workplace. In summary, it
      becomes evident that bright light has a strong direct and independent effect on
      cognitive performance, particularly on working memory and concentration.

PMID- 23117331
TI  - Dextro-transposition of the great arteries in a neonate with ventricular septal
      defect and pulmonary stenosis complicated by premature closure of the ductus
      arteriosus and possible pathophysiology of both defects.
AB  - Premature closure of the ductus arteriosus (PCDA) and transposition of the great
      arteries (TGA) cause persistent pulmonary hypertension of the newborn (PPHN). We
      present a case of a newborn who demonstrated d-TGA with ventricular septal defect
      (VSD) and pulmonary stenosis (PS) complicated by PCDA. The neonate showed severe
      cyanosis resistant to resuscitation soon after birth, and was diagnosed with d
      TGA with VSD by echocardiography. PPHN was also suspected based on physical
      symptoms and results of echocardiography. The neonate was given inhaled nitric
      oxide, prostaglandin E1, and catecholamines under sedation, and underwent a
      balloon atrial septostomy (BAS). His condition gradually improved, and he was
      extubated on day 7, but his pulmonary subvalvular stenosis gradually worsened and
      pulmonary blood flow was markedly decreased. A second BAS was performed on day 27
      and he showed no improvement. Blalock-Taussig shunt surgery was performed on day
      34, which markedly improved his condition. The co-existence of d-TGA and PCDA is
      generally a lethal state. In our patient, an increase in pulmonary blood flow
      during the fetal period was restricted because of PS and outlet flow from the
      left ventricle to the right ventricle via the VSD. This restricted blood flow
      through the ductus arteriosus, which led to narrowing of the DA. At the same
      time, damage to and constrictive changes of the pulmonary vessels were prevented.
      The ductus arteriosus should be carefully evaluated to exclude PCDA in cases of d
      TGA. The presence of both VSD and PS may be a prognostic factor in such cases. 

PMID- 23117330
TI  - Improved prenatal detection of congenital heart disease in an integrated health
      care system.
AB  - The reported prenatal detection rates (PDRs) for significant congenital heart
      disease (sCHD) have been suboptimal, even in the current era. Changes in prenatal
      ultrasound policy and training may lead to improved prenatal detection of sCHD.
      This study analyzed the results of a policy to assess fetal cardiac outflow
      tracts shown by screening prenatal ultrasound using the electronic medical record
      (EMR). During a 6-year period, fetuses and patients younger than 1 year with sCHD
      were identified. The EMR was used to gather detection and outcome data. As an
      internal control within the same health care system, the PDR of only the surgical
      cases was compared with that of a similar group in which documentation of the
      fetal cardiac outflow tracts was not standard policy. Among 25,666 births, sCHD
      was identified in 93 fetuses or patients, yielding an incidence of 3.6 per 1,000
      births. The PDR was 74.1%. Detection after birth but before discharge was 20.4%,
      and detection after discharge was 5.4%. A significant improvement in the PDR of
      sCHD was found when a concerted effort was made to obtain fetal cardiac outflow
      tract views during pregnancy screening (59.3 vs. 28%). Within an integrated
      health care system and with the use of an EMR, a PDR of 74% can be obtained, and
      94% of sCHD can be detected before discharge. A concerted program that includes
      documentation of fetal cardiac outflow tracts in the pregnancy screening can
      result in improved PDR of sCHD.

PMID- 23117332
TI  - Compositional properties characterizing commonly transported oils and controlling
      their fate in the marine environment.
AB  - Oil spills relating to shipping incidents remain of substantial concern with
      respect to marine pollution. Whilst most frequently a reactive approach is
      adopted in post-incident monitoring (for the specific product involved), this
      paper reports important physical and compositional characteristics of commonly
      transported oils and oil products to afford pro-active assessments. These
      properties include specific gravity, viscosity, elemental composition and, of
      particular relevance, the relative class compositions between aliphatics,
      aromatics, resins and asphaltenes. The latter were determined experimentally
      using thin layer chromatography with flame ionization detection. Diagnostic
      ratios of specific compounds are reported, statistically analysed, and their
      significance in identification of different oil types and the weathering
      processes is discussed. The influence of the properties on fates under different
      environmental conditions (selected to represent contrasting European regional
      seas) are examined using the NOAA Automated Data Inquiry for Oil Spills (ADIOS2)
      model. Relative contributions of the different environmental conditions and
      properties to the fate of the oil at sea are discussed.

PMID- 23117334
TI  - Superbug hideout: finding MRSA in U.S.wastewater treatment plants.

PMID- 23117333
TI  - Kalopanaxsaponin B inhibits LPS-induced inflammation by inhibiting IRAK1 Kinase.
AB  - The stem bark of Kalopanax pictus Nakai (KP, family Araliaceae), of which main
      constituent is kalopanaxsaponin B, has been used for inflammation in Chinese
      traditional medicine. We isolated kalopanaxsaponin B from KP and investigated its
      anti-inflammatory effect in lipopolysaccharide (LPS)-stimulated peritoneal
      macrophages and on LPS-stimulated systemic inflammation in male ICR mice.
      Kalopanaxsaponin B inhibited the expression of TNF-alpha, IL-1beta, iNOS and COX
      2 in LPS-stimulated peritoneal macrophages. Kalopanaxsaponin B also inhibited the
      activation of IRAK1, IKK-beta, NF-kappaB and MAP kinases (ERK, JNK, p-38).
      Treatment with LPS in the presence of kalopanaxsaponin B inhibited LPS-induced
      IRAK1 degradation and phosphorylation. Kalopanaxsaponin B inhibited IRAK1 kinase
      binding activity. However, kalopanaxsaponin B did not inhibit the NF-kappaB
      activation in active IKK-beta-transfected macrophages. Kalopanaxsaponin B did not
      inhibit the binding of LPS on toll-like receptor-4 of the macrophages.
      Kalopanaxsaponin B inhibited LPS-induced systemic inflammation in mice. Based on
      these findings, kalopanaxsaponin B ameliorates LPS-induced systemic inflammation
      by inhibiting IRAK1 kinase.

PMID- 23117335
TI  - Effect of tumor gangliosides on tyrosine phosphorylation of p125FAK in platelet
      adhesion to collagen.
AB  - The exact mechanisms as to how platelets influence blood-borne metastasis remain
      poorly understood. Gangliosides, sialic acid-containing glycosphingolipids, are
      associated with tumor progression and metastasis in humans. Gangliosides isolated
      from tumor cells promote collagen-stimulated platelet aggregation and ATP
      secretion and enhance platelet adhesion to immobilized collagen. Gangliosides
      interact with a number of cell surface receptors including integrin receptors. In
      this study, we examined the effects of alpha2beta1 integrin-mediated platelet
      adhesion to collagen and phosphotyrosine signaling of focal adhesion kinase,
      p125FAK (FAK). platelets pre-incubated with neuroblastoma tumor gangliosides
      (NBTGs) or their major component GD2 (disialoganglioside) were more adherent to
      immobilized collagen (OD570 0.43+/-0.12, 0.39+/-0.13) compared to platelets pre
      incubated with MTB (0.14+/-0.06, p<0.001); the effect of NBTGs was blocked by F
      17 anti-alpha2 antibody. Pre-incubation of platelets with NBTGs resulted in a
      marked increase in the phosphotyrosine content of p125FAK in the adherent
      platelets compared to the MTB-pre-incubated adherent platelets. F-17 anti-alpha2
      antibody decreased protein tyrosine phosphorylation of NBTG-incubated platelets
      adherent to collagen. These results indicate that the tumor gangliosides enhance
      platelet adhesion to extracellular matrix collagen by upregulating integrin
      alpha2beta1-mediated tyrosine phosphorylation of p125FAK, thereby providing
      insight into how this interaction may be involved in neuroblastoma metastasis.

PMID- 23117336
TI  - Benign metastasizing leiomyoma of the lung: report of a case.
AB  - A 35-year-old female presented with multiple bilateral pulmonary nodules on a
      chest X-ray during a regular health checkup. Chest computed tomography revealed
      multiple well-defined nodular shadows in the lung. She had undergone a myomectomy
      7 years previously for leiomyoma of the uterus. Thoracoscopic resection of one of
      the nodules was performed to establish a pathological diagnosis. Pathological
      findings were consistent with benign metastasizing leiomyoma. Estrogen and
      progesterone receptors showed strong positives by immunohistostaining of the
      tumor. The patient is currently receiving outpatient treatment for a benign
      metastasizing leiomyoma by administration of a GnRH analog drug. 

PMID- 23117337
TI  - Thermal stability of electrodeposited platinum nanowires and morphological
      transformations at elevated temperatures.
AB  - Pt nanowires were prepared by template electrodeposition using ion track etched
      polymer membranes and analysed with respect to their thermal stability. Driven by
      Rayleigh instability, the polycrystalline Pt nanostructures experienced
      structural transformations and finally fragmented into linear chains of
      nanospheres at temperatures much below the melting point of bulk Pt.
      Morphological changes were systematically studied by electron microscopy and
      compared with previously reported results on other metal nanowires and
      theoretical predictions. In addition, nanowires could readily be interconnected
      to two-dimensional assemblies by taking advantage of the rapid diffusion
      processes. This study will help to predict the durability of integrated nanowires
      and contributes to the understanding of thermal-induced transformations for
      polycrystalline nanowires.

PMID- 23117338
TI  - Housework Will Not Prevent Death in Middle Age but Sports and DIY Might.

PMID- 23117339
TI  - Do the short-term benefits of physical training for sport-related groin injuries
      persist?

PMID- 23117340
TI  - Does accelerated rehabilitation affect knee joint laxity after ACL
      reconstruction?

PMID- 23117341
TI  - Prevalence of osteoarthritis and arthroplasty in the hip and knee of former elite
      athletes.

PMID- 23117342
TI  - ECG-triggered non-enhanced MR angiography of peripheral arteries in comparison to
      DSA in patients with peripheral artery occlusive disease.
AB  - OBJECT: The purpose of this study was to evaluate peripheral non-enhanced-MRA (NE
      MRA) acquired with a 3D Turbo Spin Echo sequence with electrocardiographt (ECG)
      triggering in comparison to Digital Subtraction Angiography (DSA) as the gold
      standard in symptomatic peripheral artery occlusive disease (PAOD) patients.
      MATERIALS AND METHODS: This IRB approved prospective study included 23 PAOD
      patients from whom three patients had to be excluded. The remaining 20 subjects
      were included in the analysis (15 male; mean age 62.4 +/- 15.3 years). The
      patients first underwent DSA followed by NE-MRA on a 1.5-T whole body scanner
      within 24 h after the DSA study. A NATIVE (Non-contrast Angiography of the
      Arteries and Veins) SPACE (Sampling Perfection with Application Optimized
      Contrast by using different flip angle Evolution) sequence at four levels
      (pelvis, upper leg, knee region and lower leg) was acquired. For evaluation
      purposes, subtracted standardized MIP (maximum intensity projection) images were
      generated from the NE-MRA data sets. Qualitative assessment of NE-MRA images in
      reference to the corresponding DSA images, as well as blinded stenosis grading of
      preselected segments in NE-MRA images were performed by two experienced readers.
      Image quality in 95 corresponding arterial segments was rated from 1 (good) to 4
      (inadequate) directly comparing the NE-MRA with the corresponding DSA segment as
      the gold standard. Blinded stenosis grading consisted of 66 preselected stenoses
      rated from 1 (<10 %) to 4 (>90 %) in NE-MRA which were compared to the grade in
      the corresponding DSA. RESULTS: The mean image quality of NE-MRA in comparison to
      DSA was 2.7 +/- 1.1 (reader 1) and 3.0 +/- 1.0 (reader 2). The kappa value
      indicating interobserver agreement was 0.34; readers 1 and 2 rated the image
      quality as good in 21 % and 3 %, sufficient in 19 % and 41 %, limited in 29 % and
      14 % and inadequate in 31 % and 42 %, respectively. Stenosis graduation revealed
      significantly higher grades in NE-MRA (reader 1: 3.0 +/- 0.7, p < 0.001 and
      reader 2: 3.1 + 0.8, p < 0.001) compared to DSA (mean value DSA 2.7 +/- 0.8). The
      kappa value indicating interobserver agreement concerning stenosis grading was
      0.59. CONCLUSION: NE-MRA revealed a relatively high number of inadequate quality
      segments. This is in line with recently published comparable studies of the
      similar SPACE NE-MRA techniques. Further advance of NE-MRA techniques remains
      desirable for patients with PAOD.

PMID- 23117344
TI  - Social costs of expanding access to evidence-based supported employment: concepts
      and interpretive review of evidence.
AB  - A recent policy analysis argued that expanding access to evidence-based supported
      employment can provide savings in major components of social costs. This article
      extends the scope of this policy analysis by placing the argument within a
      recently developed economic framework for social cost-effectiveness analysis that
      defines a program's social cost impact as its effect on net consumption of all
      goods and services. A total of 27 studies over the past two decades are reviewed
      to synthesize evidence of the social cost impacts of expanding access to the
      individual placement and support model of supported employment (IPS-SE). Most
      studies have focused primarily on agency costs of providing IPS-SE services, cost
      offsets when clients shift from "traditional" rehabilitation to IPS-SE, and
      impacts on clients' earnings. Because costs and cost offsets are similar in
      magnitude, incremental costs of expanding services to persons who would otherwise
      receive traditional services are probably small or even negative. The population
      served by an expansion could be sizable, but the feasibility of a policy
      targeting IPS-SE expansion in this way has yet to be demonstrated. IPS-SE has
      positive impacts on competitive job earnings, but these may not fully translate
      into social cost offsets. Additional empirical support is needed for the argument
      that large-scale expansion would yield substantial mental health treatment cost
      offsets. Other gaps in evidence of policy impacts include take-up rate estimates,
      cost impact estimates from longer-term studies (exceeding two years), and longer
      term studies of whether IPS-SE prevents younger clients from becoming recipients
      of Supplemental Security Income or Social Security Disability Insurance

PMID- 23117345
TI  - Evaluation of acupuncture for cancer symptoms in a cancer institute in Brazil.
AB  - INTRODUCTION: Acupuncture has been progressively included in the practice of
      mainstream medicine in recent decades. The State of Sao Paulo Cancer Institute is
      a public hospital established in 2008 and its acupuncture service follows the
      experience and model of several oncology centres in the USA, aiming to optimise
      the treatment of symptoms such as postoperative pain, oncological pain,
      neuropathic pain, nausea, vomiting, xerostomia and fatigue induced by
      chemotherapy. This paper describes the population given acupuncture treatment and
      the effects of the intervention on symptom management. METHODS: One hundred and
      eighty-three patients from our service were enrolled in the study. Baseline and
      final symptom intensity was recorded using a visual analogue score (VAS) ranging
      from 0 to 10 cm, with a higher score meaning higher symptom intensity. RESULTS:
      Fifty-four (29.50%) were receiving active treatment with chemotherapy and/or
      radiotherapy, 29 (15.85%) were receiving hormone therapy and 100 (54.65%) were
      considered to be in remission. The main symptoms were: oncological pain in 44
      (24.04%), chemotoxicity in 34 (18.6%), lumbar pain in 53 (28.96%) and chronic
      postoperative pain in 54 (28.4%). The mean (SD) initial symptom score was 7.04
      (1.8), which was reduced to 2.56 (2.75) after treatment (p<0.001), an improvement
      of 63.6% in control of the symptoms. Further analysis of the data showed that the
      effect was similar in different indications for acupuncture treatment.
      CONCLUSIONS: Use of acupuncture may have improved symptom control in patients
      enrolled in this study.

PMID- 23117343
TI  - Delayed hepatic signal recovery on ferucarbotran-enhanced magnetic resonance
      images: an experimental study in rat livers with gadolinium chloride-induced
      Kupffer cell damage.
AB  - OBJECTIVE: Hepatic signal recovery, rather than reduction, in ferucarbotran
      enhanced magnetic resonance imaging (MRI) is a potential diagnostic marker of
      liver damage. We investigated hepatic signal recovery in rats with gadolinium
      chloride (GdCl3)-induced Kupffer cell (KC) damage. MATERIALS AND METHODS: Twelve
      rats received 8 MUmol iron/kg of ferucarbotran 1 day after 0-7.5 mg/kg GdCl3
      injection (experiment A). Another 12 rats received ferucarbotran followed by
      GdCl3 injection 6 h later (experiment B). In each experiment, three rats without
      GdCl3 ("no injury group") served as control. Another six rats received GdCl3
      alone without ferucarbotran. Hepatic signals were assessed on T 2 (*) -weighted
      images for up to 29 days. Iron deposits were histologically examined on day 29.
      RESULTS: Hepatic signal recovery was delayed in a GdCl3 dose-dependent manner in
      experiment A. Gadolinium chloride alone reduced hepatic signal 15 % during this
      experiment. Hepatic signal recovery was delayed only in rats that received 7.5
      mg/kg GdCl3 in experiment B. Hepatic signals negatively correlated with iron
      deposits in KCs and hepatocytes. CONCLUSION: Hepatic signal recovery on
      ferucarbotran-enhanced MRI was delayed in the context of GdCl3-induced KC damage
      due to increased hepatic iron deposits. Hepatic signal recovery may be used as a
      clinical marker of KC damage in liver disorders, including radiation-induced
      hepatitis.

PMID- 23117346
TI  - Collecting and measuring wound exudate biochemical mediators in surgical wounds.
AB  - We describe a methodology by which we are able to collect and measure biochemical
      inflammatory and nociceptive mediators at the surgical wound site. Collecting
      site-specific biochemical markers is important to understand the relationship
      between levels in serum and surgical wound, determine any associations between
      mediator release, pain, analgesic use and other outcomes of interest, and
      evaluate the effect of systemic and peripheral drug administration on surgical
      wound biochemistry. This methodology has been applied to healthy women undergoing
      elective cesarean delivery with spinal anesthesia. We have measured wound exudate
      and serum mediators at the same time intervals as patient's pain scores and
      analgesics consumption for up to 48 hours post-cesarean delivery. Using this
      methodology we have been able to detect various biochemical mediators including
      nerve growth factor (NGF), prostaglandin E2 (PG-E2) substance P, IL-1beta, IL-2,
      IL-4, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, TNFalpha, INFgamma, G-CSF, GM
      CSF, MCP-1 and MIP-1beta. Studies applying this human surgical wound bioassay
      have found no correlations between wound and serum cytokine concentrations or
      their time-release profile (J Pain. 2008; 9(7):650-7).(1) We also documented the
      utility of the technique to identify drug-mediated changes in wound cytokine
      content.

PMID- 23117347
TI  - The Osler Student Societies of the University of Texas medical branch: a medical
      professionalism translational tool.
AB  - This essay reviews some of the issues associated with the challenge of
      integrating the concepts of medical professionalism into the socialization and
      identity formation of the undergraduate medical student. A narrative-based
      approach to the integration of professionalism in medical education proposed by
      Coulehan (Acad Med 80(10):892-898, 2005) offers an appealing method to accomplish
      the task in a less didactic format and in a way that promotes more personal
      growth. In this essay, I review how the Osler Student Societies of the University
      of Texas Medical Branch developed and how they offer a convenient vehicle to
      carry out this narrative-based approach to professionalism. Through mentor
      modeled professional behavior, opportunities for student self-reflection, the
      development of narrative skills through reflection on great literature, and
      opportunities for community service, the Osler Student Societies provide a ready
      made narrative-based approach to medical professionalism education.

PMID- 23117348
TI  - Institutional contexts contribute to the low priority given to developing self
      care independence in a rehabilitation ward: a qualitative study.
AB  - OBJECTIVES: To examine the institutional contexts that contribute to the low
      priority given to the development of self-care independence in a rehabilitation
      ward. DESIGN: Research was guided by ethnographic principles of Martyn Hammersley
      and Paul Atkinson (2007). Individual in-depth interviews were completed.
      Participant observation was done daily during the rehabilitation stay of the
      patients. PATIENTS: Six men and three women with neurological impairments and
      their caregivers. RESULTS: Patients' daily routines on a rehabilitation ward in
      Taiwan are described. Four prominent themes emerged from the data: (1) the
      attitudes of patients, caregivers, and staff facilitated extended rehabilitation
      stays within the first year after disability, (2) attending therapy sessions was
      the most important activity, (3) pragmatic considerations, such as 'faster and
      easier', outweighed the value of developing self-care independence, and (4)
      strategic organization of daily routines to keep therapy the priority was
      critical for daily activity. CONCLUSION: Multiple institutional factors
      jeopardize the development of self-care independence in a rehabilitation ward.
      The factors include the primacy of biomedical-oriented rehabilitation ideology,
      insurance reimbursement policies, and cultural values associated with family
      caregiving. They legitimize the low priority given to developing self-care
      independence. Therapists need to include a critical review of daily routines
      (what and how activities are carried out inside and outside of therapy clinics)
      as part of therapy regime to identify opportunities and institutional constraints
      to the development of self-care independence.

PMID- 23117349
TI  - Feasibility, safety and preliminary evidence of the effectiveness of a home-based
      exercise programme for older people with Alzheimer's disease: a pilot randomized
      controlled trial.
AB  - OBJECTIVE: To evaluate the feasibility and safety of a home-based exercise
      programme for people with Alzheimer's disease, and to provide preliminary
      evidence of programme effectiveness in improving balance and mobility and
      reducing falls risk. DESIGN: A randomized controlled trial. SETTING: Community.
      PARTICIPANTS: Forty people with mild to moderate Alzheimer's disease (mean age
      81.9, SD 5.72; 62.5% female). INTERVENTIONS: Participants were randomized to a
      six-month home-based individually tailored balance, strengthening and walking
      exercise programme (physiotherapist) or a six-month home-based education
      programme (control) (occupational therapist). Both programmes provided six home
      visits and five follow-up phone calls. MAIN MEASURES: Balance, mobility, falls
      and falls risk were measured at baseline and programme completion. Intention-to
      treat analysis using a generalized linear model with group allocation as a
      predictor variable was performed to evaluate programme effectiveness. Feasibility
      and adverse events were systematically recorded at each contact. RESULTS: Fifty
      eight per cent of the exercise group finished the programme, completing an
      average of 83% of prescribed sessions, with no adverse events reported.
      Functional Reach improved significantly (P = 0.002) in the exercise group (mean
      (SD), 2.28 (4.36)) compared to the control group (-2.99 (4.87)). Significant
      improvement was also observed for the Falls Risk for Older People - Community
      score (P = 0.008) and trends for improvement on several other balance, mobility,
      falls and falls risk measures for the exercise group compared to the control
      group. CONCLUSIONS: The exercise programme was feasible and safe and may help
      improve balance and mobility performance and reduce falls risk in people with
      Alzheimer's disease.

PMID- 23117351
TI  - [Intraoperative thracoscopic needle biopsy for the diagnosis of indeterminate
      pulmonary tumor].
AB  - To define the usefulness of intraoperative thracoscopic needle biopsy( ITNB), we
      compared the background and operative outcomes of the patients underwent ITNB
      with those of the patients underwent partial lung resection(PLR)using auto-suture
      devices. Between 2002 and 2009, 78 patients were diagnosed as lung carcinoma by
      intraoperative pathological examination (IPE) and subsequently performed curative
      surgery. In these 78 patients, 31 underwent ITNB (NB group)first and 47 underwent
      PLR (PR group) first. The tumor size, distance between tumor and pleura, number
      of required auto-suture devices and duration time of surgery in NB group were
      34.5+/-15.6 mm, 9.2+/-8.6 mm, 4.2+/-1.5 and 276+/-47 minutes, respectively. Those
      in PR group were 27.8+/-14.2 mm, 7.1+/-6.8 mm, 5.5+/-2.0 and 286+/-61 min utes,
      respectively. The number of required auto-suture devices in NB group was
      significantly fewer than that in PR group (p<0.01).The accuracy of IPE was 93.5%
      and local recurrences weren't observed in NB group. ITNB prior to PLR for the
      patients with indeterminate lung tumor economizes the auto-suture devices and
      time required for PLR, so this method might contribute to save the operative cost
      and duration.

PMID- 23117350
TI  - Does social support impact depression in caregivers of adults ageing with spinal
      cord injuries?
AB  - OBJECTIVE: The objective of this study was to examine the role of social support
      in predicting depression in caregivers of adults aging with spinal cord injuries.
      DESIGN: Cross-sectional secondary data analyses were conducted for this study.
      SETTING: Participants were recruited from multiple community locations in
      Pittsburgh, PA and Miami, FL. SUBJECTS: Community-dwelling caregivers of aging
      adults with spinal cord injuries (N = 173) were interviewed as part of a
      multisite randomized controlled trial. MAIN MEASURES: The Center for
      Epidemiological Studies Depression Scale measured caregiver depression symptom
      levels. A hierarchical multiple regression analysis examined the effect of social
      support (social integration, received social support, and negative social
      interactions) on depressive symptom levels for the caregivers of adults aging
      with spinal cord injuries, controlling for demographic characteristics, and
      caregiving characteristics. RESULTS: Caregivers were, on average, 53 years old
      (SD = 15) and care-recipients were 55 years old (SD = 13). Average Center for
      Epidemiological Studies Depression Scale scores indicated that 69 (40%) of
      caregivers had significant depressive symptoms (mean 8.69, SD = 5.5). Negative
      social interactions (beta = 0.27, P< 0.01) and social integration ( beta = -0.25,
      P< 0.01) were significant independent predictors of depressive symptom levels in
      caregivers of adults aging with spinal cord injuries. CONCLUSIONS: Findings
      demonstrate that negative social interactions and social integration are
      associated with the burden in caregivers of adults aging with spinal cord
      injuries. Negative social interactions and social integration should be
      investigated in assessments and interventions intended to target caregiver
      depressive symptom levels.

PMID- 23117352
TI  - [Efforts to achieve anastomosis forms in coronary artery bypass grafting; cuff
      like and skirt-like anastomoses].
AB  - As the type of anastomotic site is considered to be one of the decisive factors
      for graft-patency in coronary artery bypass grafting(CABG),our aim is to achieve
      anastomosis forms that potentially promote long-term graft-patency rates. When an
      arterial graft is used, side-to-side anastomosis is performed, with its incision
      length being longer than that of the coronary artery, to achieve a cuff-like
      anastomosis form. When a vein graft is used, on the other hand, it is incised
      shorter than the coronary artery to achieve a skirt-like anastomosis form instead
      of a purse-like one. It is thus expected that reliable anastomosis forms can be
      observed in postoperative angiography.

PMID- 23117353
TI  - [Operative invasiveness of off-pump coronary artery bypass grafting].
AB  - OBJECTIVE: In our institution, steroid is administrated intravenously during the
      anesthesia induction for conventional coronary artery bypass grafting( CABG) to
      prevent the inflammatory response due to cardiopulmonary bypass and reperfusion
      injury, however, steroid is not used for off-pump CABG (OPCAB) with expectation
      of less invasiveness of the procedure. We evaluated the early outcomes and
      postoperative inflammatory response of conventional CABG with preoperative
      steroid use and OPCAB. METHODS: From May 2004 to April 2010, 120 patients
      underwent elective CABG requiring the ventricle elevation to expose the target
      vessels. Twenty eight patients(group C)treated with conventional CABG and 92
      patients (group O) with OPCAB. Perioperative course was analyzed and compared
      between the 2 groups. RESULTS: OPCAB had several advantages such as shorter
      operative duration, decreased requirement of blood transfusion and myocardial
      protection compared with conventional CABG. However, frequency of postoperative
      paroxysmal atrial fibrillation was similar between these techniques and early
      postoperative C-reactive protein levels were shown to be significantly higher in
      OPCAB. CONCLUSIONS: OPCAB has advantage over conventional CABG in blood loss
      during surgery and myocardial protection. However the inflammatory response was
      significantly severe in OPCAB. OPCAB might become less invasive with the anti
      inflammatory medication.

PMID- 23117354
TI  - [Capillary hemangiomas of the lung presenting as ground glass opacities by high
      resolution computed tomography].
AB  - Capillary hemangiomas are often seen on the skin, mucosa, liver and other organs,
      but they are very rare in the lung. We report 3 cases of capillary hemangioma of
      the lung that presented as ground glass opacities(GGO) by computed tomography(
      CT). Mixed GGO was observed in 2 cases that increased in size after the follow-up
      period. The remaining case involved a pure GGO that was stable in size. They were
      suspected to be bronchioloalveolar carcinoma( BAC) based on the CT findings, and
      video assisted thoracoscopic surgery was performed in all 3 cases. It is
      difficult to distinguish capillary hemangioma from other malignant diseases such
      as BAC based on CT findings. As high resolution CT becomes more widely used, GGOs
      are becoming more frequently detected. When GGOs are detected by CT, capillary
      hemangiomas should be included in the differential diagnosis. Intraoperatively,
      an important surgical finding for capillary hemangiomas is that they became
      impalpable after repeated palpation. This surgical finding can be useful when
      identifying the region for biopsy and resection.

PMID- 23117355
TI  - [Micronodular thymoma with lymphoid stroma(MNT)].
AB  - We report a surgical case of MNT, which is a rare type of thymoma. A 56-year-old
      man was referred to our hospital for examination of a mass in the anterior
      mediastinum. The computed tomography (CT) scan showed a lobulated mass with
      relatively smooth margins. Also, contrast study indicated homogeneous
      enhancement. Since these findings suggested the possibility of thymoma, the
      patient underwent thymothymomectomy. Histological findings showed short
      spindleshaped tumor cells forming nests of various sizes, and lymphoid stroma
      with lymphoid follicles. The pathological diagnosis was MNT. The long-term
      outcome after resection of MNT currently remains unclear, and accumulation of
      further cases is required.

PMID- 23117356
TI  - [Mycotic aneurysm of the descending thoracic aorta].
AB  - A 55-year-old man was admitted with severe back pain and saccular aneurysm of the
      descending aorta on computed tomography. Laboratory examinations showed elevated
      serum C-reactive protein of 16.98 mg/dl. Graft replacement of the descending
      thoracic aorta was performed on an emergency basis, and a latissimus dorsi muscle
      flap was wrapped around the implanted graft. Because Streptococcus pneumoniae was
      detected in the resected tissue, proper antibiotic therapy was administrated. The
      patient recovered uneventfully, without any sign of infection.

PMID- 23117357
TI  - [Stanford type a acute aortic dissection with pectus excavatum].
AB  - Pectus excavatum is generally an isolated abnormality of the chest wall. However,
      some patients have a concomitant pectus deformity and cardiac & aortic disease.
      Decisions must be made regarding the operative approach and whether the pectus
      excavatum should be corrected during the same session. We report 2 patients with
      acute Stanford type A aortic dissection and pectus excavatum who underwent
      emergency operation. In case 1, median sternotomy is an unsuitable approach for
      open heart surgery, since the heart and great vessels are displace into the left
      hemithorax. But combined sternotomy and left anterior thoracotomy provided
      excellent surgical exposure. In case 2, we proceeded with a leftsided costotomy
      of four ribs and place a normal chest retractor providing as excellent exposure
      as combined sternotomy and left anterior thoracotomy. A left-sided costotomy of
      four ribs can be performed safely, eliminating the risks of median sternotomy in
      acute stanford type A aortic dissection with pectus excavatum.

PMID- 23117358
TI  - [Primary cardiac leiomyosarcoma originating from the left atrium].
AB  - Primary malignant cardiac tumors occur extremely rarely. Among these,
      leiomyosarcomas are exceptionally rare. We described a case of left atrial
      leiomyosarcoma in which surgical intervention was followed by adjuvant radiation
      therapy. A 74-year-old male was admitted for dyspnea. Chest X-ray showed severe
      pulmonary congestion. Echocardiography revealed large tumor in the left atrium.
      Emergency operation was performed. The tumor invaded the left atrial wall and the
      mitral valve, and the lesion was resected as extensively as possible.
      Postoperative pathologic examination confirmed leiomyosarcoma. He underwent
      adjuvant radiotherapy postoperatively. However, early local recurrence was
      recognized. He died due to sudden circulatory collapse in 8th postoperative
      month. As cardiac leiomyosarcomas have extremely poor prognosis, complete
      resection and effective postoperative adjuvant therapy are necessary.

PMID- 23117359
TI  - [Minute pulmonary meningothelial-like nodules (MPMNs) incidentally detected at
      surgical biopsy for ground-glass opacity( GGO)].
AB  - A 75-year-old woman was followed up at the urology department of our hospital
      after left nephrectomy for renal cell carcinoma. Chest computed tomography (CT)
      showed ground-glass opacity in the right lower lobe( S6), 6 mm in size, in
      December 2010. 3 months later, the tumor was enlarged and she was introduced to
      our department. Wedge resection was performed to establish giagnosis.
      Pathological diagnosis was atypical adenomatous hyperplasia( AAH) and many small
      spindle-shaped cell nests were found at the same tissue. Immunohistochemically,
      this nest was shown to be minute pulmonary meningothelial-like nodules(MPMNs).
      MPMNs are asymptomatic small pulmonary nodules incidentally found during
      pathologic evaluation of pulmonary specimens. Combinations of MPMNs with
      adenocarcinoma or AAH have been reported, and the genetic relation of MPMNs and
      AAH is suggested.

PMID- 23117360
TI  - [Benign pulmonary mass suspected of primary lung cancer for the high level of Pro
      gastrin-releasing peptide(ProGRP)].
AB  - A 71-year-old male consulted a physician for a chest abnormal shadow detected by
      mass screening. As computed tomography (CT) revealed a nodular shadow in the left
      upper lobe, he was referred to our hospital. Positron emission tomography (PET)
      showed high-level accumulation of fluorodeoxy glucose (FDG) at the same site, and
      the level of Pro gastrin-releasing peptide(ProGRP) as a tumor marker was
      high(59.5 pg/ml). The level of ProGRP increased to 83.0 pg/ml 2 months later and
      the surgery was performed to make a diagnosis, however, historological
      examination during surgery by both needle biopsy and partial resection showed no
      malignancy. A final diagnosis of fibrosis associated with anthracosis was made,
      and neither active inflammation nor neoplastic lesion was not demonstrated. At 2
      years and 2 months postoperatively, the level of ProGRP was still high(58.5
      pg/ml). Although the high level of ProGRP is well known as a useful marker for
      the diagnosis of lung small cell carcinoma, some patients with renal dysfunction,
      pneumonia, interstitial pneumonia, pleurisy, or lung carcinoma that is not small
      cell carcinoma are also positive for ProGRP. Since the present case showed a mild
      impairment of renal function, it was suggested that the cause of the high level
      of ProGRP was other than lung cancer.

PMID- 23117361
TI  - [Modified Aubert procedure for transposition of the great artery with Planche
      type ii coronary anatomy;report of a case].
AB  - Unusual coronary patterns such as single, intramural, and interarterial
      coronaries are the major risk factors for the arterial switch operation. Of the
      many approaches described, modified Aubert technique for coronary reconstruction
      is one of the flexible and safer procedure in complex coronary configulations. We
      report a successful modified Aubert operation for transposition of the great
      artery associated with Planche type II coronary anatomy characterized by" single"
      and" interarterial" coronary arising from a posterior sinus. It is technically
      important to keep the sewing line of the coronary pouch away from the left margin
      of the coronary orifice. Since the interarterial coronary anatomy is a risk
      factor of future coronary events even after a successful Aubert procedure, a long
      term follow up is important.

PMID- 23117362
TI  - [Thoracoabdominal aortic thrombi as a source of peripheral embolization; report
      of a case].
AB  - We reported a case of peripheral embolization arising from diffuse 
      thoracoabdominal aortic thrombi with minimal evidence for atherosclerosis or
      other aortic pathology. After the patient was treated with anticoagulation
      therapy, surgical removal of peripheral embolus was performed.

PMID- 23117363
TI  - [Recurrence of cardiac myxoma in the left atrial after 28 years; report of a
      case].
AB  - We presented a rare surgical case of recurrent multiple left atrial myxomas, who
      had a history of surgery for multiple left ventricular myxomas 28 years ago. The
      case was a 42-year-old female. She developed dyspnea, cough, and palpitation due
      to functional mitral valve obstruction by myxoma. There were a 30 mm large
      pedunculated tumor on the left atrial septum and 2 small tumors near the orifice
      of the right upper pulmonary vein. These tumors were excised with the left atrial
      endothelium and the defect was reconstructed with a bovine pericardium.

PMID- 23117364
TI  - [A suspicious case of metastasis to the stomach from primary lung cancer; report
      of a case].
AB  - A 82-year-old man consulted for therapy for lung cancer in March 2010. Chest
      computed tomography (CT) showed a mass in right lower lobe of the lung.
      Fluorodeoxyglucose-positron emission tomography (FDG-PET) showed the accumulation
      in the mass. Lung cancer was strongly suspected and anticancer chemotherapy was
      started. The patient complained of difficulty in swallowing in August 2011.
      Gastroendoscopy revealed a submucosal mass in the gastric corpus. The specimen
      from the mass showed gastric metastasis from lung cancer on pathological study.
      The case of gastric metastasis from lung cancer is rare. When we concern the
      patient of lung cancer, it should be considered gastric metastasis.

PMID- 23117365
TI  - [Sarcoidosis with right middle lobe atelectasis initially suspected of malignant
      lymphoma; report of a case].
AB  - 60-year-old woman was admitted with an abnormal shadow on the chest
      roentgenogram. Computed tomography showed atelectasis of the right middle lobe
      and hilar and mediastinal lymphadenopathy. Bronchoscopic examination revealed an
      obstruction at the orifice of the right middle lobe bronchus and biopsy was
      performed. The biopsy suggested malignant lymphoma. A diagnosis of methotrexate
      associated lymphoproliferative disorders was suspected because the patient was
      administered methotrexate to treat the rheumatoid arthritis. The video-assisted
      thoracoscopic surgery was performed. Histological examination showed no
      malignancy and sarcoidosis in the peribronchial lymph nodes. The compressed
      middle lobe bronchus by enlarged lymph nodes was consider to be the cause of the
      middle lobe atelectasis.

PMID- 23117367
TI  - A hypervalent iodine-mediated spirocyclization of 2-(4-hydroxybenzamido)acrylates
      -unexpected formation of delta-spirolactones.
AB  - On the way towards a new total synthesis of (S)-arogenate, a novel aryl-lambda(3)
      iodane-mediated oxidative spirocyclization of para-substituted phenol derivatives
      has been discovered. Starting from easy accessible 2-(4
      hydroxybenzamido)acrylates we could construct spirocyclic lactams in up to 52%
      yield. Under alternative reaction conditions the same precursors underwent an
      unexpected oxidative spirocyclization yielding a novel delta-spirolactone in up
      to 70% yield.

PMID- 23117366
TI  - Airway pepsin levels in otherwise healthy surgical patients receiving general
      anesthesia with endotracheal intubation.
AB  - BACKGROUND: Airway pepsin has been increasingly used as a potentially sensitive
      and quantifiable biomarker for gastric-to-pulmonary aspiration, despite lack of
      validation in normal control subjects. This study attempts to define normal
      levels of airway pepsin in adults and distinguish between pepsin A (exclusive to
      stomach) and pepsin C (which can be expressed by pneumocytes). METHODS: We
      performed a prospective study of 51 otherwise healthy adult patients undergoing
      elective extremity orthopedic surgery at a single tertiary-care academic medical
      center. Lower airway samples were obtained immediately following endotracheal
      intubation and just prior to extubation. Total pepsin and pepsin A concentrations
      were directly measured by an enzymatic activity assay, and pepsin C was
      subsequently derived. Pepsinogen/pepsin C was confirmed by Western blot analyses.
      Baseline characteristics were secondarily compared. RESULTS: In all, 11 (22%; 95%
      CI = 9.9%-33%) had detectable airway pepsin concentrations. All 11 positive
      specimens had pepsin C, without any detectable pepsin A. Pepsinogen/pepsin C was
      confirmed by Western blot analyses. In a multivariate logistic regression, men
      were more likely to have airway pepsin (OR, 12.71, P = .029). CONCLUSIONS:
      Enzymatically active pepsin C, but not the gastric-specific pepsin A, is
      frequently detected in the lower airways of patients who otherwise have no risk
      for aspiration. This suggests that nonspecific pepsin assays should be used and
      interpreted with caution as a biomarker of gastropulmonary aspiration, as
      pepsinogen C potentially expressed from pneumocytes may be detected in airway
      samples.

PMID- 23117368
TI  - Timing of definitive treatment of femoral shaft fractures in patients with
      multiple injuries: a systematic review of randomized and nonrandomized trials.
AB  - BACKGROUND: Optimal timing of definitive treatment of femoral shaft fractures in
      patients with multiple injuries remains controversial. This study aimed to
      determine the impact of timing of definitive treatment (early, delayed, or damage
      control orthopedics [DCO]) of femoral shaft fractures on the incidence of adult
      respiratory distress syndrome (ARDS), mortality rate, and hospital length of stay
      (LOS) in patients with multiple injuries. METHODS: A systematic review of
      published English-language reports using MEDLINE (1946-2011), Embase (1947-2011),
      and Cochrane Library. Search terms included femoral fractures, multiple trauma,
      fracture fixation, and time factors. This study reviewed randomized and
      nonrandomized studies that (1) compared early and delayed treatment or early
      treatment and DCO and (2) reported the incidence of ARDS, mortality rate, or LOS.
      Extraction of articles was performed by one of the authors using predefined data
      fields. RESULTS: Thirty-eight studies met our inclusion criteria. Studies were
      grouped into heterogeneous injuries with early versus delayed treatment (17
      studies), heterogeneous injuries with early versus DCO (8 studies), head injury
      (13 studies), and chest injury (7 studies). Most of the studies (>= 50%)
      reporting ARDS and mortality rate showed no difference in each of these groups.
      However, 6 of 7 and 2 of 3 studies reporting LOS in the heterogeneous injuries
      with early versus delayed and heterogeneous injuries with early versus DCO,
      respectively, showed shorter stay for early treatment. Pooled analyses were not
      conducted owing to changes in critical care delivery during the study period and
      variations in definitions of early treatment, ARDS, and multiple injuries. Thirty
      five reports were based on nonrandomized trials and were subject to biases
      inherent in retrospective studies. The review process was limited by language and
      publication status. CONCLUSION: The literature suggests that early definitive
      treatment may be used safely for most patients with multiple injuries. However, a
      subgroup of patients with multiple injuries may benefit from DCO [corrected].
      LEVEL OF EVIDENCE: Systematic review, level III.

PMID- 23117369
TI  - Management of dabigatran-induced anticoagulation in trauma and acute care surgery
      patients.

PMID- 23117370
TI  - Editorial critique.

PMID- 23117371
TI  - Emergency department thoracotomies: is it time we took them to the field?

PMID- 23117372
TI  - Editorial critique.

PMID- 23117373
TI  - Damage control resuscitation: early decision strategies in abdominal gunshot
      wounds using an easy "ABCD" mnemonic.
AB  - BACKGROUND: Early damage-control resuscitation (DCR) indicators have not been
      clearly discerned in patients with penetrating abdominal trauma. Our objective
      was to identify these clinical indicators that could standardize a DCR initiation
      policy in this subset of patients. METHODS: Prospective data collection from
      January 2003 to October 2010 at a Level I trauma center in Cali, Colombia. All
      adult (>15 years) patients with abdominal gunshot wounds (GSWs) were included.
      They were divided into two groups: those who underwent DCR and those who did not.
      Both groups were compared by demographics, clinical variables, severity scores,
      and overall mortality. Other scores were compared with our newly devised model
      using the area under the receiver operating characteristic curve (AUROC).
      RESULTS: There was a total of 331 abdominal GSWs. Of these, a total of 162 (49%)
      underwent DCR. The overall mortality was 11.2%. Multivariate analysis identified
      (A) acidosis (base deficit >= 8); (B) blood loss (hemoperitoneum > 1,500 mL); (C)
      cold (temperature < 35  degrees C); (D) damage (New Injury Severity Score > 35)
      as significant clinical indicators that aided in the decision process of early
      implementation of DCR. The Trauma-Associated Severe Hemorrhage (AUROC, 0.8333),
      McLaughlin (AUROC, 0.8148), ABC (AUROC, 0.7372) scores and our ABCD mnemonic
      (AUROC, 0.8745) were all good predictors of DCR, and the difference between them
      was statistically significant (p < 0.001). CONCLUSION: We have identified (A)
      acidosis (base deficit >= 8); (B) blood loss (hemoperitoneum > 1,500 mL); (C)
      cold (temperature < 35  degrees C); (D) damage (New Injury Severity Score > 35)
      as significant clinical indicators that aided in the decision process of early
      implementation of DCR for patients with abdominal GSWs. LEVEL OF EVIDENCE:
      Prognostic/epidemiologic study, level III.

PMID- 23117374
TI  - Infections after trauma are associated with subsequent cardiac injury.
AB  - BACKGROUND: Trauma produces profound inflammatory and immune responses. A second
      hit such as an infection further disrupts the inflammatory cascade. Inflammatory
      responses, following traumatic injuries, infections, or both, are emerging as
      biologic mediators of cardiac disease including myocardial ischemia and
      infarction. Inflammation-induced and stress-related cardiac damage are
      increasingly recognized in patients with critical illness. It is believed that
      cardiac dysfunction is the result of alterations in the inflammatory and immune
      cascades. Urinary tract infections (UTIs) and ventilator-associated pneumonia
      (VAP) are associated with increased mortality in trauma patients. UTIs and VAPs
      induced inflammatory responses. We postulate that increased mortality seen in
      trauma patients with infections is caused by increased rates of cardiac injury.
      METHODS: This is a retrospective review of prospectively collected data. All
      trauma patients admitted to the intensive care unit at our Level I trauma center
      during 5 years were included in the analysis. Proportional hazard regression
      analysis was performed to predict suspicion of cardiac injury (troponin ordered),
      any cardiac injury (troponin > 0.15 ng/mL), or severe cardiac injury (troponin >
      1 ng/mL) using age, sex, Injury Severity Score (ISS), pulmonary disease (chronic
      obstructive pulmonary disease), heart failure, hypertension, diabetes, and the
      presence of a UTI or VAP. A similar proportion hazard regression was performed to
      predict mortality. RESULTS: In the model to predict any cardiac injury, chronic
      obstructive pulmonary disease (hazards ratio [HR], 1.9; p = 0.02), ISS (HR, 1.01;
      p = 0.04), VAP (HR, 5.6; p < 0.01), and UTI (HR, 2.4; p = 0.03) were significant.
      Neither VAP nor UTI predicted severe cardiac injury. In the model to predict
      death, any cardiac injury was not associated with mortality, but severe cardiac
      injury and UTI were associated with mortality as age increased. CONCLUSION:
      Infectious complications have been associated with increased mortality in trauma
      patients. Our data demonstrate that development of VAP or UTI is associated with
      an increased risk of developing cardiac injury in trauma patients, which may
      contribute to subsequent increased mortality. LEVEL OF EVIDENCE:
      Prognostic/epidemiologic study, level III.

PMID- 23117375
TI  - The effect of dead-on-arrival and emergency department death classification on
      risk-adjusted performance in the American College of Surgeons Trauma Quality
      Improvement Program.
AB  - BACKGROUND: The American College of Surgeons' Trauma Quality Improvement Program
      is focused on identifying variations in outcomes across trauma centers for the
      purposes of performance improvement. In previous analyses, patients who died in
      the emergency department were excluded. We investigated the effect of inclusion
      and exclusion of emergency department (ED) deaths (dead on arrival [DOA] and died
      in ED [DIE]) on analyses of overall risk-adjusted trauma center performance.
      METHODS: Data for patients admitted to 65 Trauma Quality Improvement Program
      hospitals during the 2009 calendar year was used. A logistic regression model was
      developed to estimate risk-adjusted mortality. Trauma centers were then ranked
      based on their observed-to-expected (O/E) mortality ratio with 90% confidence
      intervals (CIs) and classified by outlier status: low outliers/high performers
      had a 90% CI for O/E mortality ratio of less than 1, and high outliers/low
      performers had a 90% CI for O/E mortality ratio of greater than 1. Changes in
      outlier status, rank, and quartile were examined with and without DOA and DIE
      patients included in the analyses to discern the impact of such exclusions on
      overall risk-adjusted center-specific performance. RESULTS: Thirty-one trauma
      centers (48%) reported no DOA patients in 2009, while 6 centers (9%) reported
      more than 10. Of 224 patients, 14 (6.2%) had a documented time of death of more
      than 30 minutes after ED arrival despite being recorded as DOA. Forty-one trauma
      centers (63%) changed rank by three positions or less. Ten trauma centers changed
      their quartile ranking by a single quartile, but no centers were found to change
      quartile rank more than one quartile. Changes in outlier status occurred for 6
      trauma centers (9%). CONCLUSION: The relative frequency of patients classified as
      DOA varies greatly between trauma centers. Misclassification of patients as DOA
      occurs. Inclusion of ED deaths in risk-adjusted analysis of mortality results in
      a small but insignificant change in predicting the outcome results of a trauma
      center. This change is less than the rate of finding a center to be a high or low
      outlier by chance alone using the 90% CI. Inclusion of DOA and DIE patients in
      risk-adjusted analysis of mortality is appropriate and eliminates the bias
      introduced by exclusion of ED deaths owing to misuse of the DOA classification.
      LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III.

PMID- 23117376
TI  - Undiagnosed medical comorbidities in the uninsured: a significant predictor of
      mortality following trauma.
AB  - BACKGROUND: Lack of health care insurance has been correlated with increased
      mortality after trauma. Medical comorbidities significantly affect trauma
      outcomes. Access to health care and thereby being diagnosed with a pretrauma
      comorbidity is highly dependent on insurance status. The objective of this study
      was to determine whether rates of diagnosed or undiagnosed preexisting
      comorbidities significantly contribute to disparities in mortality rates observed
      between insured and uninsured trauma patients. METHODS: Review of trauma patients
      admitted to a Level I trauma center during a 5-year period. Data extracted from
      the registry included age, sex, Injury Severity Score (ISS), comorbidities,
      mortality, and insurance status. Multivariate logistic regression analysis was
      performed using age, sex, and insurance status to predict comorbidities and age,
      sex, ISS, and insurance status to predict mortality. RESULTS: Insured patients
      were older (54 years vs. 38, p < 0.001) and more likely female (41.3% vs. 22.5%,
      p < 0.001). When adjusting for age and sex, insured patients were more likely to
      have a pretrauma diagnosis of coronary artery disease (odds ratio [OR], 2.09; 95%
      confidence interval [CI], 1.54-2.83), diabetes mellitus (OR, 2.09; 95% CI, 1.61
      2.72), hypertension (OR, 1.97; 95% CI, 1.65-2.35), asthma/emphysema (OR, 1.64;
      95% CI, 1.32-2.04), neurologic problems (OR, 1.79; 95% CI, 1.31-2.44), and
      gastroesophageal reflux disease (OR, 2.03; 95% CI, 1.33-3.11), compared with
      patients without insurance. In the analysis to predict mortality, having
      insurance was protective (OR, 0.57; 95% CI, 0.45-0.71). Among patients with no
      diagnosed comorbidities, insured patients had the lowest mortality risk (OR, 0.5;
      95% CI, 0.38-0.67). When analyzing only patients with diagnosed comorbidities,
      insurance status had no impact on mortality risk (OR, 0.81; 95% CI, 0.53-1.22).
      CONCLUSION: Undiagnosed preexisting comorbidities play a crucial role in
      determining outcomes following trauma. Diagnosis of medical comorbidities may be
      a marker of access to health care and may be associated with treatment, which may
      explain the gap in mortality rates between insured and uninsured trauma patients.
      LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III.

PMID- 23117377
TI  - Suppression of the p66shc adapter protein by protocatechuic acid prevents the
      development of lung injury induced by intestinal ischemia reperfusion in mice.
AB  - BACKGROUND: Intestinal ischemia/reperfusion (I/R) causes severe histological
      injury, reactive oxygen species activation, and cell apoptosis in the lung. In
      this study, we investigated, using a murine intestinal I/R model, the effect of a
      polyphenolic compound, protocatechuic acid (PCA), in modulation of ShcA and in
      protection of the lung from I/R-induced injury. METHODS: Fifty ICR mice were
      randomly divided into five groups, including a control group, intestinal I/R
      group, control + PCA group, I/R + PCA low-dose group, and I/R + PCA high-dose
      group. The I/R and I/R + PCA groups were subjected to mesenteric arterial
      ischemia for 45 minutes and reperfusion for 90 minutes. The control and control +
      PCA groups underwent a surgical procedure that included isolation of the superior
      mesenteric artery without occlusion. In all PCA-pretreated groups, the mice
      received intraperitoneal PCA administration for three consecutive days. Serum
      specimens were collected for measuring tumor necrosis factor-alpha and
      interleukin 6, while lung tissues were harvested for histopathologic assessment
      including glutathione (GSH) and GSH peroxidase assay. Lung expression of p66shc,
      phosphorylated p66shc, manganese superoxide dismutase, caspace-3, and Bcl-xL were
      determined by Western blotting for protein level and semiquantitative reverse
      transcription-polymerase chain reaction analysis for mRNA level. RESULTS: PCA
      pretreatment markedly reduced I/R-induced lung injury as indicated by
      histological alterations; the decreases in tumor necrosis factor-alpha,
      interleukin 6, and caspase-3 expression levels; and the increases in GSH, GSH
      peroxidase, manganese superoxide dismutase, and Bcl-xL levels in the lung.
      Moreover, PCA treatment down-regulated p66shc expression and phosphorylation.
      CONCLUSION: PCA has a significant protective effect in lung injury induced by
      intestinal I/R. The protective effect of PCA may be attributed to the suppression
      of p66shc and the modulation of downstream antioxidative/antiapoptotic factors.

PMID- 23117378
TI  - Rho-kinase-dependent F-actin rearrangement is involved in the release of
      endothelial microparticles during IFN-alpha-induced endothelial cell apoptosis.
AB  - BACKGROUND: Activation of cytoskeleton regulator Rho-kinase during inflammatory
      stimulations plays a major role in cellular dysfunction and apoptosis. Because
      endothelial dysfunction may be influenced by increased circulating membrane
      microparticles (MPs), we hypothesized that inhibition of Rho-kinase can prevent
      interferon-alpha (IFN-alpha)-induced endothelial cell (EC) apoptosis and that
      protective effects of Rho-kinase inhibition are facilitated by prevention of F
      actin rearrangement. METHODS: In this study, Lewis rats were subjected to an
      intraperitoneal injection of IFN-alpha or IFN-alpha + Y-27632. FCM was performed
      to analyze circulating endothelial MPs (EMPs) from the blood samples of these
      animals by detecting the expression of CD144, CD62E, CD31, CD51, and CD54 on
      EMPs. IFN-alpha-induced pulmonary injury was assessed by measurement of lung wet
      to-dry weight ratios and measurement of alveolar wall thickness. Human pulmonary
      microvascular ECs (HPMECs) were cultured with IFN-alpha or EMPs to elucidate the
      probable mechanisms of the release of EMPs. RESULTS: Injection of IFN-alpha
      resulted in much higher levels of CD144 EMPs, CD62E EMPs, CD31 EMPs, CD51 EMPs,
      and CD54 EMPs. Pulmonary injury was also observed after injection of IFN-alpha.
      Furthermore, IFN-alpha induced F-actin rearrangement and apoptosis of HPMECs in
      vitro, and the Toll-like receptor 4/MyD88 and nuclear factor-kappaB pathways and
      EMPs per se played important roles in this process. CONCLUSION: The results
      demonstrate that increased Rho-kinase activity causes the release of EMPs and
      cellular apoptosis. Moreover, HPMEC apoptosis that resulted from EMP stimulation
      indicates that EMPs can be considered as a potential target to regulate the
      rearrangement of cytoskeleton during endothelial cell apoptosis.

PMID- 23117379
TI  - Negative-pressure wound therapy: a hemostatic adjunct for control of
      coagulopathic hemorrhage in large soft tissue wounds.
AB  - BACKGROUND: Negative-pressure wound therapy has been commonly used for treating
      chronic wounds and recently applied for treatment of traumatic wounds. We
      investigated the potential hemostatic benefit of negative-pressure wound therapy
      for control of refractory hemorrhage in a soft tissue wound model in swine.
      METHODS: Coagulopathy was induced in pigs (n = 38, 36 kg) by hemodilution and
      hypothermia. Next, a large soft tissue wound (diameter, approximately 20 cm) was
      created by slicing the gluteus maximus muscle. Free bleeding was allowed for 1
      minute, and wounds were then randomly dressed with either laparotomy gauze (G)
      alone or TraumaPad (TP, a kaolin-coated dressing) alone or in combination with
      negative pressure (NP, approximately -500 mm Hg). All wounds were sealed with
      adhesive drapes. Fluid resuscitation was administered and targeted to mean
      arterial pressure of 60 mm Hg. Pigs were observed for 150 minutes or until death
      after which tissues were sampled for histologic examination. RESULTS: Induced
      coagulopathy as measured by increases in prothrombin time (12%) and activated
      partial thromboplastin time (22%) and decreases in fibrinogen (48%) were similar
      in all groups. There were no differences in initial bleeding rates (4.5
      mL/kg/min). Dressing the wounds with G or TP produced hemostasis only in one pig
      (1 of 18 pigs). Addition of NP to these dressings secured hemostasis in 70% (G)
      and 90% (TP) of animals with average hemostasis time of 34 minutes and 25
      minutes, respectively. Blood losses and fluid resuscitation requirements were
      significantly less, and survival times were significantly longer in NP adjunct
      groups than in the other groups. Survival rates were 80% (G+NP) and 90% (TP+NP)
      versus 0% (G) and 10% (TP) in the respective groups. Histologic examination
      showed similar superficial myofibril damages in all groups. CONCLUSION: To our
      knowledge, the present data provide the first evidence that NP serves as an
      effective hemostatic adjunct and when combined with standard hemostatic dressing
      it is able to stop lethal coagulopathic bleeding in large soft tissue wounds.

PMID- 23117380
TI  - Impact of prehospital hypothermia on transfusion requirements and outcomes.
AB  - BACKGROUND: Prehospital hypothermia (PH) is known to increase mortality following
      traumatic injury. PH relationship with transfusion requirements has not been
      documented. The purpose of this investigation was to analyze the impact of PH on
      blood product requirements and subsequent outcomes. METHODS: The Los Angeles
      County Trauma System Database was queried for all patients admitted between 2005
      and 2009. Demographics, physiologic parameters, and transfusion requirements were
      obtained and dichotomized by admission temperatures with a core temperature of
      less than 36.5  degrees C considered hypothermic. Multivariate analysis was
      performed to determine factors contributing to transfusion requirements and to
      derive adjusted odds ratios (AORs) for mortality and rates of adult respiratory
      distress syndrome and pneumonia. RESULTS: A total of 21,023 patients were
      analyzed in our study with 44.6% presenting with PH. Hypothermic patients
      required 26% more fluid resuscitation (p < 0.001) in the emergency department and
      17% more total blood products (p < 0.001) than those who were admitted with a
      normal temperature. There was a trend toward an increase in emergency department
      transfusion (8%, p = 0.06). PH was independently associated with the need for a
      transfusion (AOR, 1.1; p = 0.047), increased mortality (AOR, 2.0; p < 0.01), as
      well as incidence of adult respiratory distress syndrome (AOR, 1.8; p < 0.05) and
      pneumonia (AOR, 2.6; p < 0.01). CONCLUSION: PH is associated with increased
      transfusion and fluid requirements and subsequently worse outcomes. Interventions
      that correct hypothermia may decrease transfusion requirements and improve
      outcomes. Prospective studies investigating correction of hypothermia in trauma
      patients are warranted. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level
      III.

PMID- 23117381
TI  - Nasal cannula end-tidal CO2 correlates with serum lactate levels and odds of
      operative intervention in penetrating trauma patients: a prospective cohort
      study.
AB  - BACKGROUND: Penetrating trauma patients in shock often require urgent operative
      intervention. Studies have demonstrated that variables obtained in the emergency
      department, such as lactate levels, can help the physician determine the presence
      of hemorrhagic shock, leading to more rapid intervention and improve prognosis in
      trauma patients. The purpose of the study is to determine if end-tidal (ET) CO2
      correlates with serum lactate levels, a measure of tissue hypoxia and
      subsequently shock, in penetrating trauma patients. Secondarily, we sought to
      determine whether ET CO2 could be used to determine the patient's odds of
      requiring operative intervention. METHODS: A prospective observational cohort
      study was undertaken at an urban Level 1 trauma center. Baseline ET CO2 from
      nasal cannula and serum lactate level were recorded in all patients in whom the
      trauma team was activated. Outcomes defined were whether operative intervention
      was needed. Pearson correlation (R), correlation coefficient (r(2)), and odds
      ratio were calculated. RESULTS: One hundred five patients were enrolled. Pearson
      correlations and coefficients calculated for serum lactate level to ET CO2 were R
      = -0.86 (r(2) = 0.74, p < 0.0001). Of patients requiring operative intervention,
      81.97% had abnormally low ET CO2 and 54.1% had abnormally high serum lactate
      levels. Odds ratios of patients needing an emergent operation with abnormally low
      ET CO2 was 20.4 (95% confidence interval, 7.47-55.96) and with abnormally high
      serum lactate levels was 4 (95% confidence interval, 1.68-5.93). CONCLUSION: ET
      CO2 has a strong inverse correlation to serum lactate levels. Abnormally low ET
      CO2 values were associated with greater increased odds compared with serum
      lactate levels of penetrating trauma patients requiring operative intervention.
      LEVEL OF EVIDENCE: Prognostic/diagnostic study, level I.

PMID- 23117382
TI  - The splenic artery stump pressure is affected by arterial anatomy after proximal
      embolotherapy in blunt splenic injury.
AB  - BACKGROUND: Proximal splenic artery embolotherapy can be used as an adjunct to
      nonoperative management of blunt splenic injury (BSI); however, the hemodynamic
      changes in the distal splenic artery after proximal splenic artery occlusion are
      unknown. METHODS: A retrospective review of 48 patients who underwent transient
      occlusion of the proximal splenic artery with distal splenic artery pressure
      measurements was performed. Patients were grouped into those with celiac artery
      stenosis and those with normal celiac anatomy as determined by contrast-enhanced
      computed tomography. RESULTS: Celiac stenosis was identified in 12 (25.0%) of the
      48 patients. The celiac stenosis and normal anatomy groups were not statistically
      different in their systolic pressure, diastolic pressure, mean arterial pressure,
      age, sex, and splenic injury grade. Transient occlusion of the proximal splenic
      artery resulted in a decreased distal splenic artery systolic pressure, diastolic
      pressure, and mean arterial pressure and a decreased systolic and mean perfusion
      gradient in all patients (42.6 +/- 20.8 mm Hg, 39.7 +/- 17.8 mm Hg, 40.9 +/- 18.9
      mm Hg, 67.4 +/- 14.5%, and 55.4 +/- 17.9%, respectively). The distal splenic
      artery stump pressure values in the celiac stenosis and normal anatomy patients
      differed significantly (72.7 +/- 32.0 mm Hg vs. 36.7 +/- 11.2 mm Hg, 66.6 +/-
      26.5 mm Hg vs. 34.4 +/- 9.3 mm Hg, 69.0 +/- 27.9 mm Hg vs. 35.5 +/- 10.2 mm Hg,
      46.1 +/- 19.7% vs. 71.6 +/- 8.9%, 28.8 +/- 21.6% vs. 60.6 +/- 11.7%, for systolic
      pressure, diastolic pressure, mean arterial pressure, systolic gradient, and mean
      gradient in celiac stenosis and normal anatomy BSI patients, respectively; all
      values of p < 0.0001). CONCLUSION: In hemodynamically stable BSI patients, the
      systolic pressure in the distal splenic artery is decreased by an average of 67%
      after proximal splenic artery embolotherapy; however, the pressure reduction in
      those patients with celiac stenosis is significantly less. This finding may
      explain some postembolotherapy delayed splenic hemorrhage events. LEVEL OF
      EVIDENCE: Prognostic/epidemiologic study, level III; therapeutic study, level IV.

PMID- 23117383
TI  - Assessment of workload during pediatric trauma resuscitation.
AB  - BACKGROUND: Trauma resuscitations are high-pressure, time-critical events during
      which health care providers form ad hoc teams to rapidly assess and treat injured
      patients. Trauma team members experience varying levels of workload during
      resuscitations resulting from the objective demands of their role-specific tasks,
      the circumstances surrounding the event, and their individual previous
      experiences. The goal of this study was to determine factors influencing workload
      experienced by trauma team members during pediatric trauma resuscitations.
      METHODS: Workload was measured using the National Aeronautics and Space
      Administration Task Load Index (TLX). TLX surveys were administered to four
      trauma team roles: charge nurse, senior surgical resident (surgical coordinator),
      emergency medicine physician, and junior surgical resident or nurse practitioner
      (bedside clinician). A total of 217 surveys were completed. Univariate and
      multivariate statistical techniques were used to examine the relationship between
      workload and patient and clinical factors. RESULTS: Bedside clinicians reported
      the highest total workload score (208.7), followed by emergency medicine
      physicians (156.3), surgical coordinators (144.1), and charge nurses (129.1).
      Workload was higher during higher-level activations (235.3), for events involving
      intubated patients (249.0), and for patients with an Injury Severity Score
      greater than 15 (230.4) (p, 0.001 for all). When controlling for potential
      confounders using multiple linear regression, workload was increased during
      higher level activations (79.0 points higher, p = 0.01) and events without
      previous notification (38.9 points higher, p = 0.03). Workload also remained
      significantly higher for the bedside clinician compared with the other three
      roles (p <= 0.005 for all). CONCLUSION: Workload during pediatric trauma
      resuscitations differed by team role and was increased for higher-level
      activations and events without previous notification. This study demonstrates the
      validity of the TLX as a tool to measure workload in trauma resuscitation. LEVEL
      OF EVIDENCE: Prognostic study, level II.

PMID- 23117384
TI  - Blast injury in children: an analysis from Afghanistan and Iraq, 2002-2010.
AB  - BACKGROUND: Throughout history, children have been victims of armed conflict,
      including the blast injury complex, however, the pattern of injury, physiologic
      impact, and treatment needs of children with this injury are not well documented.
      METHODS: The Joint Theatre Trauma Registry provides data on all civilians
      admitted to US military treatment facilities from 2002 to 2010 with injuries from
      an explosive device. The data were stratified by age and analyzed for differences
      in anatomic injury patterns, Injury Severity Score (ISS), Revised Trauma Score
      (RTS), mortality, intensive care unit days, and length of hospitalization.
      Multivariate logistic regression was done to determine independent predictors of
      mortality. All operative procedures with a specified site were tabulated and
      categorized by body region and age. RESULTS: A total of 4,983 civilian patients
      were admitted, 25% of whom were younger than 15 years. Pediatric patients aged 8
      to 14 years had a higher ISS and hospital stay than other age groups, and
      children younger than 15 years had a longer intensive care unit stay. Injuries in
      children were more likely to occur in the head and neck and less likely in the
      bony pelvis and extremities. Children had a lower RTS than the other age groups.
      Mortality correlated highly with burns, head injury, transfusion, and RTS.
      Adolescent patients had a lower mortality rate than the other age groups.
      Improvised explosive devices were the most common cause of injury in all age
      groups. CONCLUSION: Children experiencing blast injury complex have an anatomic
      pattern that is unique and an RTS that reflects more severe physiologic
      derangement. Injuries requiring transfusion or involving the head and neck and
      burns were predictive of mortality, and this persisted across all age groups. The
      mortality rate of children with blast injury is significant (7%), and treatment
      is resource intensive, requiring many surgical subspecialties. LEVEL OF EVIDENCE:
      Epidemiologic study, level III.

PMID- 23117385
TI  - Early albumin use improves mortality in difficult to resuscitate burn patients.
AB  - BACKGROUND: The optimal resuscitation algorithm remains elusive for patients with
      a large burn injury. Recent reports from the military support that larger burns
      that do not respond well to ongoing lactated Ringer's solution resuscitation may
      improve with the use of 5% albumin and vasopressors. We hypothesized that the use
      of 5% albumin and vasopressors, as needed, would decrease complications of fluid
      resuscitation and burn mortality. METHODS: Fluid needs during the first 24 hours
      after burn injury, complications, and demographics were collected from all
      patients 12 years and older with burn size 20% or more of total body surface area
      admitted from 2003 to 2010. In March 2007, we changed our resuscitation to
      include the use of 5% albumin in the first 24 hours if the estimated fluid needs
      at 12 hours after burn would lead to a fluid volume of 6 mL/kg per percent burn
      at 24 hours. The patients treated before this change (Preprotocol) were compared
      with those treated after the guideline change (Postprotocol). RESULTS: The two
      groups were well matched for age, burn size, and inhalation injury. Ventilator
      days and mortality were decreased in the Postprotocol group. There was a trend
      toward less intravenous fluid use in the Postprotocol group where the use of
      albumin was higher. There was significantly less vasopressor infusion in the
      Postprotocol group. There was no statistical difference in the number of
      escharotomies performed or overall incidence of abdominal compartment syndrome,
      but no patient required open laparotomy in the Postprotocol group. CONCLUSION: An
      algorithm incorporating albumin use in the first 24 hours after burn injury was
      associated with the use of less vasopressor agents and lower mortality. Early
      albumin use was also associated with a shorter duration of mechanical ventilation
      in burn patients sustaining burns 20% or more total body surface area. LEVEL OF
      EVIDENCE: Therapeutic study, level IV.

PMID- 23117386
TI  - Change of serum phosphate level and clinical outcome of hypophosphatemia in
      massive burn patient.
AB  - BACKGROUND: Hypophosphatemia is relatively common phenomenon in patients with
      massive burn injury. Therefore, we check serum phosphate level routinely and try
      to supply phosphate in a timely manner. The purpose of this study was to
      investigate the change of the serum phosphate level of early postburn period and
      the impact of hypophosphatemia on the prognosis of patients. METHODS: A total of
      227 patients with burn injury were reviewed retrospectively. We performed
      analysis of serum phosphate level within 20 days from burn injury. RESULTS:
      Patients' mean (SD) age was 47.0 (14.1) years, and mean (SD) percentage of total
      body surface area burned were 47.7 (21.9). Severe hypophosphatemia (phosphate <
      1.0 mg/dL) was observed in 35 patients (15.8%), and moderate hypophosphatemia
      (1.0 <= phosphate < 2.0 mg/dL) was found in 115 patients (50.6%). Therefore,
      overall incidence of hypophosphatemia was 66.4%. There was no significant
      difference in serum phosphate level with survival, total body surface area
      burned, and mechanical ventilation. Age (odds ratio [OR], 3.180; 95% confidence
      interval [CI], 1.025-9.871; p = 0.045), total body surface area burned (OR,
      20.934; 95% CI, 6.845-64.024; p = 0.000), and mechanical ventilation (OR, 5.581;
      95% CI, 2.380-13.085; p = 0.002) were independently associated with mortality.
      However, serum phosphate level (OR, 0.828; 95% CI, 0.275-2.495; p = 0.737) does
      not have a statistical significance. CONCLUSION: Although multiple studies have
      evaluated the efficacy and safety of phosphate repletion regimens, the effect on
      mortality and morbidity is not well reported. However, our results show that
      patients with massive burn injury have high incidence of hypophosphatemia, and
      hypophosphatemia can result in many complications. Therefore, routine check and
      supply of phosphate can be suggested in patients with massive burn injury. LEVEL
      OF EVIDENCE: Prognostic study, level II.

PMID- 23117387
TI  - Editorial critique.

PMID- 23117388
TI  - Socioeconomic deprivation and associated risk factors of traumatic brain injury
      in children.
AB  - BACKGROUND: This study aimed to investigate the relative risks of low income
      (family socioeconomic deprivation) and associated factors for traumatic brain
      injury (TBI) in children. METHODS: Using Taiwan National Health Insurance
      Research Database and adjusting the covariates, we conducted a population-based
      case-control study analyzing 8,291 pediatric patients, aged 0 year to 17 years,
      diagnosed with TBI, and 33,164 sex- and age-matched controls to study the
      association of low income and TBI. The relative risks of TBI for
      socioeconomically deprived children with various coexisted medical conditions
      were evaluated. RESULTS: After adjustment, pediatric population with low income
      were at increased risk of TBI (odds ratio [OR], 1.71; 95% confidence interval
      [CI], 1.52-1.92). Among the coexisting medical conditions, low-income pediatric
      population with mental disorders had significantly increased TBI risk when
      compared with matched controls (adjusted OR, 1.99; 95% CI, 1.51-2.63). Increased
      risk of TBI was also found in low-income children with epilepsy when compared
      with children of regular family income (adjusted OR, 3.11; 95% CI, 1.65-5.86).
      The adjusted OR of TBI for low-income children with mental disorders and epilepsy
      was as high as 4.45 (95% CI, 1.96-10.1). Among TBI patients, low-income children
      who had epilepsy were at significantly higher risk of post-TBI intracranial
      hemorrhage when compared with controls (OR, 10.6; 95% CI, 3.30-33.9). CONCLUSION:
      We found a significantly increased risk of TBI in socioeconomically deprived
      children, particularly among children with mental disorders, epilepsy, or both.
      Low-income children should be considered for special attention to reduce TBI risk
      and post-TBI morbidities. LEVEL OF EVIDENCE: Prognostic study, level III.

PMID- 23117389
TI  - An evidence-based review: efficacy of safety helmets in the reduction of head
      injuries in recreational skiers and snowboarders.
AB  - BACKGROUND: Approximately 600,000 ski- and snowboarding-related injuries occur in
      North America each year, with head injuries accounting for up to 20% of all
      injuries. Currently, there are no major institutional recommendations regarding
      helmet use for skiers and snowboaders in the United States, in part owing to
      previous conflicting evidence regarding their efficacy. The objective of this
      review was to evaluate existing evidence on the efficacy of safety helmets during
      skiing and snowboarding, particularly in regard to head injuries, neck and
      cervical spine injuries, and risk compensation behaviors. These data will then be
      used for potential recommendations regarding helmet use during alpine winter
      sports. METHODS: The PubMed, Cochrane Library, and EMBASE databases were searched
      using the search string helmet OR head protective devices AND (skiing OR
      snowboarding OR skier OR snowboarder) for articles on human participants of all
      ages published between January 1980 and April 2011. The search yielded 83, 0, and
      96 results in PubMed, Cochrane Library, and EMBASE, respectively. Studies
      published in English describing the analysis of original data on helmet use in
      relation to outcomes of interest, including death, head injury, severity of head
      injury, neck or cervical spine injury, and risk compensation behavior, were
      selected. Sixteen published studies met a priori inclusion criteria and were
      reviewed in detail by authors. RESULTS: Level I recommendation is that all
      recreational skiers and snowboarders should wear safety helmets to reduce the
      incidence and severity of head injury during these sports. Level II
      recommendation/observation is that helmets do not seem to increase risk
      compensation behavior, neck injuries, or cervical spine injuries among skiers and
      snowboarders. Policies and interventions to increase helmet use should be
      promoted to reduce mortality and head injury among skiers and snowboarders.
      CONCLUSION: Safety helmets clearly decrease the risk and severity of head
      injuries in skiing and snowboarding and do not seem to increase the risk of neck
      injury, cervical spine injury, or risk compensation behavior. Helmets are
      strongly recommended during recreational skiing and snowboarding.

PMID- 23117390
TI  - Acute traumatic subdural hematoma: current mortality and functional outcomes in
      adult patients at a Level I trauma center.
AB  - BACKGROUND: Existing data on outcomes following subdural hematoma have provided
      limited information on medical complications and functional outcomes. Mortality
      rates previously reported range from 22% to 66%. METHODS: This is a retrospective
      cohort study of prospectively collected data from a trauma registry in Washington
      State from 2005 through 2008. Patients were categorized by surgical evacuation
      status with the hypothesis that those undergoing evacuation represented a more
      severe injury. RESULTS: The 1,427 patients included in the study had a mean age
      of 58 years, and most of them were male (63%). Glasgow Coma Scale (GCS) score on
      presentation was greater than 12 in 58%; the average Injury Severity Score (ISS)
      was 27.5. Mean length of stay was 9.6 days (range, 1-110), with 40% spending 2 or
      more days in the intensive care unit. Twenty-eight percent experienced medical
      complications. At discharge, 94% had GCS score of 13 or greater. Independence
      with expression, feeding, and locomotion at discharge was noted for 92%, 81%, and
      43%, respectively. Inpatient mortality was 16% and did not differ significantly
      between the evacuated group (15%) and the nonevacuated group (17%). CONCLUSION:
      This large cohort of patients with acute traumatic subdural hematoma demonstrated
      a lower mortality rate than those of previous reports, including among patients
      requiring surgical evacuation (J Trauma Acute Care Surg. 2012;73:1348-1352).
      LEVEL OF EVIDENCE: Epidemiologic study, level III.

PMID- 23117391
TI  - An EST dataset for Metasequoia glyptostroboides buds: the first EST resource for
      molecular genomics studies in Metasequoia.
AB  - The "living fossil" Metasequoia glyptostroboides Hu et Cheng, commonly known as
      dawn redwood or Chinese redwood, is the only living species in the genus and is
      valued for its essential oil and crude extracts that have great potential for
      anti-fungal activity. Despite its paleontological significance and economical
      value as a rare relict species, genomic resources of Metasequoia are very
      limited. In order to gain insight into the molecular mechanisms behind the
      formation of reproductive buds and the transition from vegetative phase to
      reproductive phase in Metasequoia, we performed sequencing of expressed sequence
      tags from Metasequoia vegetative buds and female buds. By using the 454
      pyrosequencing technology, a total of 1,571,764 high-quality reads were
      generated, among which 733,128 were from vegetative buds and 775,636 were from
      female buds. These EST reads were clustered and assembled into 114,124 putative
      unique transcripts (PUTs) with an average length of 536 bp. The 97,565 PUTs that
      were at least 100 bp in length were functionally annotated by a similarity search
      against public databases and assigned with Gene Ontology (GO) terms. A total of
      59 known floral gene families and 190 isotigs involved in hormone regulation were
      captured in the dataset. Furthermore, a set of PUTs differentially expressed in
      vegetative and reproductive buds, as well as SSR motifs and high confidence SNPs,
      were identified. This is the first large-scale expressed sequence tags ever
      generated in Metasequoia and the first evidence for floral genes in this
      critically endangered deciduous conifer species.

PMID- 23117392
TI  - Arabinose-rich polymers as an evolutionary strategy to plasticize resurrection
      plant cell walls against desiccation.
AB  - A variety of Southern African resurrection plants were surveyed using high
      throughput cell wall profiling tools. Species evaluated were the dicotyledons,
      Myrothamnus flabellifolia and Craterostigma plantagineum; the monocotyledons,
      Xerophyta viscosa, Xerophyta schlecterii, Xerophyta humilis and the resurrection
      grass Eragrostis nindensis, as well as a pteridophyte, the resurrection fern,
      Mohria caffrorum. Comparisons were made between hydrated and desiccated leaf and
      frond material, with respect to cell wall composition and polymer abundance,
      using monosaccharide composition analysis, FT-IR spectroscopy and comprehensive
      microarray polymer profiling in combination with multivariate data analysis. The
      data obtained suggest that three main functional strategies appear to have
      evolved to prepare plant cell walls for desiccation. Arabinan-rich pectin and
      arabinogalactan proteins are found in the resurrection fern M. caffrorum and the
      basal angiosperm M. flabellifolia where they appear to act as 'pectic
      plasticizers'. Dicotyledons with pectin-rich walls, such as C. plantagineum, seem
      to use inducible mechanisms which consist of up-regulating wall proteins and
      osmoprotectants. The hemicellulose-rich walls of the grass-like Xerophyta spp.
      and the resurrection grass E. nindensis were found to contain highly
      arabinosylated xylans and arabinogalactan proteins. These data support a general
      mechanism of 'plasticising' the cell walls of resurrection plants to desiccation
      and implicate arabinose-rich polymers (pectin-arabinans, arabinogalactan proteins
      and arabinoxylans) as the major contributors in ensuring flexibility is
      maintained and rehydration is facilitated in these plants.

PMID- 23117393
TI  - Inoculation of Astragalus racemosus and Astragalus convallarius with selenium
      hyperaccumulator rhizosphere fungi affects growth and selenium accumulation.
AB  - Little is known about how fungi affect plant selenium (Se) accumulation. Here we
      investigate the effects of two fungi on Se accumulation, translocation, and
      chemical speciation in the hyperaccumulator Astragalus racemosus and the non
      accumulator Astragalus convallarius. The fungi, Alternaria astragali (A3) and
      Fusarium acuminatum (F30), were previously isolated from Astragalus
      hyperaccumulator rhizosphere. A3-inoculation enhanced growth of A. racemosus yet
      inhibited growth of A. convallarius. Selenium treatment negated these effects.
      F30 reduced shoot-to-root Se translocation in A. racemosus. X-ray microprobe
      analysis showed no differences in Se speciation between inoculation groups. The
      Astragalus species differed in Se localization and speciation. A. racemosus root
      Se was distributed throughout the taproot and lateral root and was 90 % organic
      in the lateral root. The related element sulfur (S) was present as a mixture of
      organic and inorganic forms in the hyperaccumulator. Astragalus convallarius root
      Se was concentrated in the extreme periphery of the taproot. In the lateral root,
      Se was exclusively in the vascular core and was only 49 % organic. These findings
      indicate differences in Se assimilation between the two species and differences
      between Se and S speciation in the hyperaccumulator. The finding that fungi can
      affect translocation may have applications in phytoremediation and
      biofortification.

PMID- 23117394
TI  - The CER22 gene required for the synthesis of cuticular wax alkanes in Arabidopsis
      thaliana is allelic to CER1.
AB  - Cuticular waxes coat the primary aerial tissues of land plants and serve as a
      protective barrier against non-stomatal water loss and various environmental
      stresses. Alkanes are the most prominent cuticular wax components and are thought
      to have an important role in controlling permeability of the cuticle. However,
      alkane biosynthesis in plants is not well understood. Arabidopsis eceriferum1
      (cer1) and cer22 mutants show dramatic reductions in alkane, secondary alcohol,
      and ketone content, and concomitant increases in aldehyde content, suggesting
      that one or both of these genes encode an alkane-forming enzyme. To determine the
      biochemical identity of CER22, and to investigate the relationship between CER1
      and CER22 in alkane formation, we mapped the cer22 mutation as a first step to
      positional cloning. Unexpectedly, mapping revealed linkage of cer22 to markers on
      chromosome 1 in the vicinity of CER1, and not to markers on chromosome 3 as
      previously reported. Failure of the cer1-1 and cer22 mutants to complement each
      other, and the presence of an allele specific mutation in the CER1 gene amplified
      from cer22 genomic DNA demonstrated that CER22 is identical to CER1. The cer22
      mutant was therefore renamed cer1-6. Analyses of CER1 transcript levels, and stem
      cuticular wax load and composition in the cer1-6 (cer22) line indicated that cer1
      6 is a weak mutant allele of CER1. This represents an important step forward in
      our understanding of alkane synthesis in plants, and will direct future research
      in the field to focus on the role of CER1 in this process.

PMID- 23117396
TI  - Autoantibody stabilization of the classical pathway C3 convertase leading to C3
      deficiency and Neisserial sepsis: C4 nephritic factor revisited.
AB  - C3 deficiency is a rare disorder that leads to recurrent pyogenic infections.
      Here we describe a previously healthy 18 y/o Caucasian male with severe
      meningococcal disease. Total hemolytic activity was zero secondary to an
      undetectable C3. The C3 gene was normal by sequencing. Mixing the patient's serum
      with normal human serum led to C3 consumption. An IgG autoantibody in the
      patient's serum was identified that stabilized the classical pathway C3 and C5
      convertases, thus preventing decay of these enzyme complexes. This autoantibody
      is an example of a C4 nephritic factor, with an additional feature of stabilizing
      the C5 convertase. Previous patients with C4 nephritic factor had
      membranoproliferative glomerulonephritis. Two years after presentation, this
      patient's C3 remains undetectable with no evidence of renal disease. We revisit
      the role of autoantibodies to classical pathway convertases in disease, review
      the literature on C4-NeF and comment on its detection in the clinical laboratory.

PMID- 23117395
TI  - Dysregulated Tim-3 expression and its correlation with imbalanced CD4 helper T
      cell function in ulcerative colitis.
AB  - The pathogenesis of ulcerative colitis (UC) remains largely unclear. Here we
      found that T-cell Ig mucin-3 (Tim-3) and its ligand, galectin 9 (Gal-9), were
      significantly decreased in UC patients and in mice with dextran sodium sulfate
      (DSS)-induced colitis compared to controls. In addition to an enhanced Th17
      response and attenuated regulatory T (Treg) cell response, there was also a
      significantly decreased Th1 response in UC. Levels of the Th1 cell chemokines
      CXCL9 and CXCL10 were significantly decreased in UC mice, partially explaining
      the decreased Th1 cell function in UC. Finally, administration of a putative
      antagonistic anti-Tim-3 antibody or of recombinant Gal-9 significantly
      exacerbated or attenuated DSS-induced colitis by altering the balance between
      different Th cell subsets. Our data suggest that a dysregulated Tim-3/Gal-9
      pathway may contribute to the pathogenesis of UC. A better understanding of this
      pathway may shed new light on the pathogenesis of this disease.

PMID- 23117397
TI  - Groundwater vulnerability assessment using fuzzy logic: a case study in the
      Zayandehrood aquifers, Iran.
AB  - Groundwater is an important source of water, especially in arid and semi-arid
      regions where surface water is scarce. Groundwater pollution in these regions is
      consequently a major concern, especially as pollution control and removal in
      these resources are not only expensive but at times impossible. It is, therefore,
      essential to prevent their contamination in the first place by properly
      identifying vulnerable zones. One method most commonly used for evaluating
      groundwater pollution is the DRASTIC method, in which the Boolean logic is used
      to rank and classify the parameters involved. Problems arise, however, in the
      application of the Boolean logic. In this paper, the fuzzy logic has been used to
      avoid the problems. For this purpose, three critical cases of minimum, maximum,
      and mean values have been considered for the net recharge parameter. The process
      has been performed on the Zayandehrood river basin aquifers. The fuzzy-DRASTIC
      vulnerability map thus obtained indicates that the western areas of the basin
      generally have the maximum pollution potential followed by the areas located in
      the east. The central parts of the study area are found to have a low pollution
      potential. Finally, two sensitivity analyses are performed to show the
      significance of each value of the net recharge parameter in the calculation of
      vulnerability index.

PMID- 23117398
TI  - Non-motorized winter recreation impacts to snowmelt erosion, Tronsen Basin,
      Eastern Cascades, Washington.
AB  - Many recreation impact studies have focused on summer activities, but the
      environmental impact of winter recreation is poorly characterized. This study
      characterizes the impact of snowshoe/cross-country ski compaction and snowmelt
      erosion on trails. Trail cross-sectional profiles were measured before and after
      the winter season to map changes in erosion due to winter recreation. Compacted
      snow on the trail was 30 % more dense than snowpack off the trail before spring
      melt out. Snow stayed on the trail 7 days longer. Soil and organic material was
      transported after spring snowmelt with -9.5 +/- 2.4 cm(2) total erosion occurring
      on the trail transects and -3.8 +/- 2.4 cm(2) total erosion occurring on the
      control transect (P = 0.046). More material was transported on the trail than on
      the control, 12.9+/- 2.4 versus 6.0 +/- 2.4 cm(2) (P = 0.055), however,
      deposition levels remained similar on the trail and on the control. Snow
      compaction from snowshoers and cross-country skiers intensified erosion. Trail
      gradient was found to be significantly correlated to net changes in material on
      the trail (R (2) = 0.89, rho = -0.98, P = 0.005). This study provides a baseline,
      showing that non-motorized winter recreation does impact soil erosion rates but
      more studies are needed. Trail managers should consider mitigation such as water
      bars, culverts and avoiding building trails with steep gradients, in order to
      reduce loss of soils on trails and subsequent sedimentation of streams.

PMID- 23117399
TI  - Evaluating water conservation and reuse policies using a dynamic water balance
      model.
AB  - A dynamic water balance model is created to examine the effects of different
      water conservation policies and recycled water use on water demand and supply in
      a region faced with water shortages and significant population growth, the Las
      Vegas Valley (LVV). The model, developed using system dynamics approach, includes
      an unusual component of the water system, return flow credits, where credits are
      accrued for returning treated wastewater to the water supply source. In LVV, Lake
      Mead serves as, both the drinking water source and the receiving body for treated
      wastewater. LVV has a consumptive use allocation from Lake Mead but return flow
      credits allow the water agency to pull out additional water equal to the amount
      returned as treated wastewater. This backdrop results in a scenario in which
      conservation may cause a decline in the available water supply. Current water use
      in LVV is 945 lpcd (250 gpcd), which the water agency aims to reduce to 752 lpcd
      (199 gpcd) by 2035, mainly through water conservation. Different conservation
      policies focused on indoor and outdoor water use, along with different population
      growth scenarios, are modeled for their effects on the water demand and supply.
      Major contribution of this study is in highlighting the importance of outdoor
      water conservation and the effectiveness of reducing population growth rate in
      addressing the future water shortages. The water agency target to decrease
      consumption, if met completely through outdoor conservation, coupled with lower
      population growth rate, can potentially satisfy the Valley's water demands
      through 2035.

PMID- 23117400
TI  - How to further develop the evidence base for transfusion medicine.

PMID- 23117401
TI  - Detection of West Nile virus RNA (lineages 1 and 2) in an external quality
      assessment programme for laboratories screening blood and blood components for
      West Nile virus by nucleic acid amplification testing.
AB  - BACKGROUND: A second Italian external quality assessment programme was run in
      2011 to assess the performance of blood transfusion centres in detecting West
      Nile virus RNA in plasma. MATERIALS AND METHODS: Each participant received two
      panels containing negative samples and samples positive for West Nile virus
      lineages 1 and 2, some of which with a viral concentration close to or below the
      95% limit of detection of the respective commercial nucleic acid amplification
      test assay: the PROCLEIX WNV assay or the Cobas TaqScreen West Nile virus test.
      RESULTS: Eleven laboratories took part in the external quality assessment
      programme. All of them correctly identified the positive samples with a viral
      concentration above the 95% limit of detection. No false positive results or pre
      /post-analytical errors were observed. DISCUSSION: The External quality
      assessment programme run in 2011 allowed participants to assess the performance
      of the nucleic acid amplification test methods applied in their seasonal routine
      screening of blood donations. The results confirm the 95% limit of detection
      reported by the test kits' manufacturers for both West Nile virus lineages.

PMID- 23117402
TI  - Successful outcome of therapeutic plasma exchange in post-partum haemolytic
      uraemic syndrome: a case report.

PMID- 23117403
TI  - Images in paediatrics: Linear scleroderma en coup de sabre and frontal lobe
      epilepsy.

PMID- 23117404
TI  - Hepatic abscess: presentation in a previously healthy teenager.

PMID- 23117405
TI  - Managing difficult issues: does training have any impact?

PMID- 23117406
TI  - Statistical analysis of life history calendar data.
AB  - The life history calendar is a data-collection tool for obtaining reliable
      retrospective data about life events. To illustrate the analysis of such data, we
      compare the model-based probabilistic event history analysis and the model-free
      data mining method, sequence analysis. In event history analysis, we estimate
      instead of transition hazards the cumulative prediction probabilities of life
      events in the entire trajectory. In sequence analysis, we compare several
      dissimilarity metrics and contrast data-driven and user-defined substitution
      costs. As an example, we study young adults' transition to adulthood as a
      sequence of events in three life domains. The events define the multistate event
      history model and the parallel life domains in multidimensional sequence
      analysis. The relationship between life trajectories and excess depressive
      symptoms in middle age is further studied by their joint prediction in the
      multistate model and by regressing the symptom scores on individual-specific
      cluster indices. The two approaches complement each other in life course
      analysis; sequence analysis can effectively find typical and atypical life
      patterns while event history analysis is needed for causal inquiries.

PMID- 23117407
TI  - A Bayesian normal mixture accelerated failure time spatial model and its
      application to prostate cancer.
AB  - In the United States, prostate cancer is the third most common cause of death
      from cancer in males of all ages, and the most common cause of death from cancer
      in males over age 75. It has been recognized that the incidence of the prostate
      cancer is high in African Americans, and its occurrence and progression may be
      impacted by geographical factors. In order to investigate the spatial effects and
      racial disparities for prostate cancer in Louisiana, in this article we propose a
      normal mixture accelerated failure time spatial model, which does not require the
      proportional hazards assumption and allows the multi-model distribution to be
      modeled. The proposed model is estimated with a Bayesian approach and it can be
      easily implemented in WinBUGS. Extensive simulations show that the proposed model
      provides decent flexibility for a variety of parametric error distributions. The
      proposed method is applied to 2000-2007 Louisiana prostate cancer data set from
      the Surveillance, Epidemiology and End Results Program. The results reveal the
      possible spatial pattern and racial disparities for prostate cancer in Louisiana.

PMID- 23117408
TI  - A Phase I/II trial design when response is unobserved in subjects with dose
      limiting toxicity.
AB  - We propose a Phase I/II trial design in which subjects with dose-limiting
      toxicity are not followed for response, leading to three possible outcomes for
      each subject: dose-limiting toxicity, absence of therapeutic response without
      dose-limiting toxicity, and presence of therapeutic response without dose
      limiting toxicity. We define the latter outcome as a 'success,' and the goal of
      the trial is to identify the dose with the largest probability of success. This
      dose is commonly referred to as the most successful dose. We propose a design
      that accumulates information on subjects with regard to both dose-limiting
      toxicity and response conditional on no dose-limiting toxicity. Bayesian methods
      are used to update the estimates of dose-limiting toxicity and response
      probabilities when each subject is enrolled, and we use these methods to
      determine the dose level assigned to each subject. Due to the need to explore
      doses more fully, each subject is not necessarily assigned the current estimate
      of the most successful dose; our algorithm may instead assign a dose that is in a
      neighborhood of the current most successful dose. We examine the ability of our
      design to correctly identify the most successful dose in a variety of settings
      via simulation and compare the performance of our design to that of competing
      approaches.

PMID- 23117409
TI  - A literature-based approach to evaluate the predictive capacity of a marker using
      time-dependent summary receiver operating characteristics.
AB  - Meta-analyses are popular tools to summarize the results of publications.
      Prognostic performances of a marker are usually summarized by meta-analyses of
      survival curves or hazard ratios. These approaches may detect a difference in
      survival according to the marker but do not allow evaluation of its prognostic
      capacity. Time-dependent receiver operating characteristic curves evaluate the
      ability of a marker to predict time-to-event. In this article, we describe an
      adaptation of time-dependent summary receiver operating characteristic curves
      from published survival curves. To achieve this goal, we modeled the marker and
      the time-to-event distributions using non-linear mixed models. First, we applied
      this methodology to individual data in kidney transplantation presented as
      aggregated data, in order to validate the method. Second, we re-analyzed a
      published meta-analysis, which focused on the capacity of KI-67 to predict the
      overall survival of patients with breast cancer.

PMID- 23117410
TI  - Cystathionine beta synthase modulates senescence of human endothelial cells.
AB  - Availability of methionine is known to modulate the rate of aging in model
      organisms, best illustrated by the observation that dietary methionine
      restriction extends the lifespan of rodents. However, the underlying mechanisms
      are incompletely understood. In eukaryotic cells, methionine can be converted to
      cysteine through the reverse transsulfuration pathway thereby modulating
      intracellular methionine availability. Whereas previous results obtained in yeast
      and fruit flies suggest that alterations in the reverse transsulfuration pathway
      modulate the rate of aging, it is not known whether this function is conserved in
      evolution. Here we show that depletion of cystathionine beta synthase (CBS), a
      rate limiting enzyme in the reverse transsulfuration pathway, induces premature
      senescence in human endothelial cells. We found that CBS depletion induces mild
      mitochondrial dysfunction and increases the sensitivity of endothelial cells to
      homocysteine, a known inducer of endothelial cell senescence and an established
      risk factor for vascular disease. Our finding that CBS deficiency induces
      endothelial cell senescencein vitro, involving both mitochondrial dysfunction and
      increased susceptibility of the cells to homocysteine, suggests a new mechanism
      linking CBS deficiency to vascular aging and disease.

PMID- 23117411
TI  - Optimum interpolation analysis of basin-scale 137Cs transport in surface seawater
      in the North Pacific Ocean.
AB  - 137Cs is one of the conservative tracers applied to the study of oceanic
      circulation processes on decadal time scales. To investigate the spatial
      distribution and the temporal variation of 137Cs concentrations in surface
      seawater in the North Pacific Ocean after 1957, a technique for optimum
      interpolation (OI) was applied to understand the behaviour of 137Cs that revealed
      the basin-scale circulation of Cs 137Cs in surface seawater in the North Pacific
      Ocean: 137Cs deposited in the western North Pacific Ocean from global fallout
      (late 1950s and early 1960s) and from local fallout (transported from the Bikini
      and Enewetak Atolls during the late 1950s) was further transported eastward with
      the Kuroshio and North Pacific Currents within several years of deposition and
      was accumulated in the eastern North Pacific Ocean until 1967. Subsequently,
      137Cs concentrations in the eastern North Pacific Ocean decreased due to
      southward transport. Less radioactively contaminated seawater was also
      transported northward, upstream of the North Equatorial Current in the western
      North Pacific Ocean in the 1970s, indicating seawater re-circulation in the North
      Pacific Gyre.

PMID- 23117412
TI  - Induction of apoptosis by D-limonene is mediated by inactivation of Akt in LS174T
      human colon cancer cells.
AB  - D-limonene is recognized as a potential chemotherapeutic agent, however, the
      details of this mechanism remain unclear. In this study, we investigated the
      effects of d-limonene on colon cancer cell viability and its potential mechanism
      of action in vitro. After 48 h of treatment, d-limonene suppressed the viability
      of LS174T cells in a dose-dependent manner and caused a dose-dependent apoptotic
      cell death. D-limonene activated caspase-3 and -9 and PARP cleavage in a dose
      dependent manner. Moreover, an increase in Bax protein and cytosol cytochrome c
      from mitochondria and a decrease in bcl-2 protein were observed following
      treatment with d-limonene. In addition, d-limonene decreased the levels of p-Akt
      (Ser473), p-Akt (Thr308) and p-GSK-3beta (Ser9), suggesting that d-limonene
      induced apoptosis via the mitochondrial death pathway and the suppression of the
      PI3K/Akt pathway.

PMID- 23117413
TI  - Here today, here tomorrow? Urinary concentrations of parabens over time.

PMID- 23117414
TI  - Photocatalytic activity of TiO2 nanoparticles: effect of thermal annealing under
      various gaseous atmospheres.
AB  - The structure, composition and photocatalytic activity of TiO(2) nanoparticles 
      annealed in various gas atmospheres (N(2), NH(3) and H(2)) were studied in this
      work. The effect of treatment on crystal structure, particle size, chemical
      composition and optical absorbance were assessed by means of x-ray diffraction,
      transmission electron microscopy, x-ray photoelectron spectroscopy and diffuse
      optical reflectance/transmittance measurements, respectively. Photocatalytic
      properties of the materials were evaluated by three different methods:
      degradation of methyl orange in water, killing of Staphylococcus aureus bacteria
      and photogeneration of radicals in the presence of 3-carboxy-2,2,5,5-tetramethyl
      pyrrolidine-1-oxyl (PCA) marker molecules. The results indicate that the
      correlation between pretreatment and the photocatalytic performance depends on
      the photocatalytic processes and cannot be generalized.

PMID- 23117415
TI  - Sizing up microbes.
AB  - The size range of life forms is dictated by basic principles of physics. Large
      microorganisms, with sizes approaching a millimeter, have compensating features
      that address the immutable laws of physics. For pathogens, size may impact a
      range of functions, such as adherence and immune evasion. We review several
      recent studies on factors impacting, and impacted by, the size of microorganisms.

PMID- 23117416
TI  - A physiologically regulated multidomain cystatin of wheat shows stage-dependent
      immunity against Karnal Bunt (Tilletia indica).
AB  - To identify novel components of basal resistance against the Tellitia indica of
      wheat, breeding for disease resistance was carried out on resistant and
      susceptible genotype of Karnal Bunt. The different members of wheat cystatin gene
      families were cloned, and their role in triggering differential resistance
      through co-expression was analyzed in our lab. The multidomain wheat cystatin
      (WCM) is a proteinase inhibitor characterized by cloning the gene from
      susceptible (WH542) and resistant genotype (HD 29). A WCM cDNA was isolated from
      both genotypes and sequenced. The WCM had a highly conserved N-terminal cystatin
      domain and a long C-terminal extension containing a second region, which
      exhibited similarity to the cystatin domain. The expression level was
      significantly (P > 0.001) higher in resistant compared to susceptible genotype at
      all the physiological stages of wheat spikes. In order to characterize the
      biochemical properties of WCM, the coding sequence was expressed in Escherichia
      coli using pET expression vector. The recombinant WCM was purified from soluble
      fraction of the cell extract by using affinity chromatography. WCM, with 23 KDa
      molecular mass, showed cysteine proteinase inhibitory activity against papain (Ki
      3.039 * 10(-7) M) as determined by using BAPNA as substrate. Furthermore, it was
      able to arrest the fungal mycelial growth of T. indica. Hyphae growth was
      inhibited, and morphological changes such as swelling and fragmentation of the
      fungus were observed. Overall, these observations suggest an endogenous high
      expression of cystatin, possibly associated with the resistance of wheat against
      Karnal bunt.

PMID- 23117417
TI  - Cloning, expression, and characterization of a recombinant esterase from cold
      adapted Pseudomonas mandelii.
AB  - A gene coding for the extracellular esterase (EstK) was cloned from the
      psychrotrophic bacterium Pseudomonas mandelii based on its partial amino acid
      sequence as determined by mass spectrometry. The entire open reading frame
      consisting of 1,011 bp was expressed in Escherichia coli as a soluble protein and
      purified by nickel-chelated affinity chromatography and Capto Q column
      chromatography. Here, we show that the 33-kDa recombinant EstK protein (rEstKsp)
      had a substrate preference for esters of short-chain fatty acids, especially, p
      nitrophenyl acetate. Optimum activity of rEstKsp was at pH 8.5 and 40  degrees C.
      The esterase activity remained similar from a range of 4~20  degrees C, but the
      maximum activity varied depending upon pH. With p-nitrophenyl acetate as the
      substrate, K (M) was 210 MUM and k (cat) was 3.4 s(-1). Circular dichroism and
      fluorescence spectroscopy results revealed that rEstKsp had a predominantly alpha
      helical structure and maintained its folded state at 4~40  degrees C.
      Interestingly, the tertiary structure of rEstKsp was predicted based on the
      structures of other hyperthermophilic esterases. Our results demonstrated that
      both native and rEstKsp are active at low temperatures and have a unique
      substrate preference for p-nitrophenyl acetate.

PMID- 23117418
TI  - Isolation and biochemical characterization of two novel metagenome-derived
      esterases.
AB  - Environmental DNA from soil and water samples was extracted to construct a
      plasmid library and a fosmid library containing 19,500 and 20,400 clones,
      respectively. Two esterases (EstP2K and EstF4K) were finally isolated from each
      library based on activity screening, and both of them were characterized in this
      study. The esterase EstF4K consists of 396 amino acids with an SMTK motif which
      belongs to family VIII esterase/lipase. The amino acid sequence of EstF4K showed
      83 % identity with that of EstA3, a reported esterase isolated from uncultured
      organisms of soil. EstP2K is composed of 224 amino acids in size and shows only
      37 % identity with a putative lipase of Neisseria elongata subsp. The purified
      EstF4K was optimally active at pH 8.0 and 50  degrees C. It was remarkably active
      and very stable in the presence of 30 % dimethyl sulfoxide. Activity fingerprint
      of EstF4K displayed a higher level of activity toward short-chain fatty acid p
      nitrophenyl (pNP) esters, while EstP2K preferred bias for pNP caprylate ester.
      The optimum reaction temperature and pH for EstP2K are 45  degrees C and 7.5,
      respectively, and the enzyme exhibited strong tolerance in the presence of 30 %
      methanol. EstF4K and EstP2K showed opposite enantioselectivity for methyl 3
      phenylglycidate, a chiral synthon for the synthesis of Taxol(r) side chain.

PMID- 23117419
TI  - Acute retinal necrosis: factors associated with anatomic and visual outcomes.
AB  - PURPOSE: To examine the factors associated with anatomic and visual outcomes in
      Japanese patients with acute retinal necrosis (ARN). METHODS: One hundred four
      patients with ARN who were followed for more than 1 year at nine referral centers
      were reviewed. Retinal involvement at initial presentation was classified into
      four groups: zone 1 (posterior pole, n = 22), zone 2 (midperiphery, n = 54), zone
      3 (periphery, n = 25), and unknown (n = 3). Forty-eight eyes underwent
      prophylactic vitrectomy before development of retinal detachment (vitrectomy
      group); 56 eyes were treated conventionally without prophylactic vitrectomy
      (observation group). RESULTS: The retina was attached in 28 of 48 eyes (58.3 %)
      in the vitrectomy group and 42 of 56 eyes (75.0 %) in the observation group at
      the final visit (P = 0.071). At 1 year, 56 eyes (53.8 %) had a best-corrected
      visual acuity (BCVA) of 20/200 or worse. Multivariate logistic regression
      analyses identified zone 1 disease (odds ratio = 4.983) and optic nerve
      involvement (odds ratio = 5.084) as significantly associated with BCVA of 20/200
      or worse. Among the zone 3 eyes, significantly (P = 0.012) more eyes in the
      observation group than in the vitrectomy group had an attached retina.
      CONCLUSIONS: Prophylactic vitrectomy did not improve the final BCVA in any eyes.
      Zone 3 eyes had better outcomes without prophylactic vitrectomy.

PMID- 23117420
TI  - Morbidity and mortality conferences in emergency departments: the French National
      Survey.
AB  - In France, emergency departments (EDs) are not yet required to implement
      Morbidity and Mortality Conferences (M&MCs), but it is likely that they will soon
      be a requirement. We conducted a national survey through e-mail to evaluate
      current M&MC practices in EDs in France. Of the 232 questionnaires sent out, 149
      responses were analyzed (64%). In total, 73 departments claimed that they carried
      out M&MCs, 36 (81.1%) at a University hospital (UH) compared with 37 departments
      (35%) at a non-UH (P < 0.001). In 29% of departments, M&MCs are held once a month
      (n = 21), in 34% every 2 months, and in 37% of departments they are held at
      longer intervals. Specialists are invited in 80% of departments (n = 58). All
      departments carrying out M&MCs finish with corrective action. The frequency with
      which M&MCs are conducted in EDs in France is low but is increasing. Currently,
      M&MCs are mainly conducted at UHs; this practice should develop in general
      hospitals as well.

PMID- 23117421
TI  - Prehospital anaesthesia by a physician and paramedic critical care team in
      Southwest England.
AB  - OBJECTIVES: Prehospital anaesthesia using rapid sequence induction (RSI) is
      carried out internationally and in the UK despite equivocal evidence of clinical
      benefit. It is a core skill of the prehospital critical care service established
      by the Great Western Ambulance Service NHS Trust (GWAS) in 2008. This
      retrospective analysis of the service's first 150 prehospital RSIs describes
      intubation success rates and complications, thereby contributing towards the
      ongoing debate on its role and safety. METHODS: Within the GWAS critical care
      team, RSI is only carried out in the presence of a qualified physician and
      critical care paramedic (CCP). The role of the intubating practitioner is
      interchangeable between physician and CCP. Data were collected retrospectively
      from RSI audit forms and electronic patient monitor printouts. RESULTS: GWAS
      physician and CCP teams undertook 150 prehospital RSIs between June 2008 and
      August 2011. The intubation success rate was 82, 91 and 97% for the first, second
      and third attempts, respectively. Successful intubation on the first attempt was
      achieved in 58 (85%) and 64 (78%) patients for physicians and CCPs, respectively.
      RSI complications included hypoxaemia (10.2%), hypotension (9.7%) and bradycardia
      (1.3%). CONCLUSION: Prehospital RSI can be carried out safely, with intubation
      success rates and complications comparable with RSI in the emergency department.
      The variation in the intubation success rates between individual practitioners
      highlights the importance of ongoing performance monitoring, coupled with high
      standards of clinical governance and training.

PMID- 23117422
TI  - Therapeutic effects of rapamycin on MPTP-induced Parkinsonism in mice.
AB  - In neurodegenerative disorders such as Parkinson's disease (PD), autophagy is
      implicated in the process of dopaminergic neuron cell death. The alpha-synuclein
      protein is a major component of Lewy bodies and Lewy neurites, and mutations in
      alpha-synuclein have been implicated in the etiology of familial PD. The current
      work investigates the mechanisms underlying the therapeutic effects of the
      autophagy-stimulating antibiotic rapamycin in the 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) mouse model of PD. Male C57BL/6 mice were treated with
      intravenous rapamycin or saline control for 7 days following MPTP administration.
      Immunohistochemistry and western blotting were used to detect alterations in the
      expression of PD biomarkers, including tyrosine hydroxylase (TH), and the level
      of autophagy was evaluated by the detection of both microtubule-associated
      protein light chain 3 (LC3) and alpha-Synuclein cleavage. In addition, levels of
      monoamine neurotransmitters were measured in the striatum using high performance
      liquid chromatography (HPLC). Immunohistochemistry using antibodies against TH
      indicated that the number of dopaminergic neurons in the substantia nigra
      following MPTP treatment was significantly higher in rapamycin-treated mice
      compared with saline-treated controls (p < 0.01). Levels of TH expression in the
      striatum were similar between the groups. alpha-synuclein Immunoreactivity was
      significantly decreased in rapamycin-treated mice compared with controls (p <
      0.01). Immunoreactivity for LC3, however, was significantly higher in the
      rapamycin-treated animals than controls (p < 0.01). The concentrations of both
      striatal dopamine, and the dopamine metabolite DOPAC, were significantly
      decreased in both MPTP-treated groups compared with untreated controls. The loss
      of DOPAC was less severe in rapamycin-treated mice compared with saline-treated
      mice (p < 0.01) following MPTP treatment. These results demonstrate that
      treatment with rapamycin is able to prevent the loss of TH-positive neurons and
      to ameliorate the loss of DOPAC following MPTP treatment, likely via activation
      of autophagy/lysosome pathways. Thus, further investigation into the
      effectiveness of rapamycin administration in the treatment of PD is warranted.

PMID- 23117423
TI  - Brief report: CANTAB performance and brain structure in pediatric patients with
      Asperger syndrome.
AB  - By merging neuropsychological (CANTAB/cambridge neuropsychological test automated
      battery) and structural brain imaging data (voxel-based-morphometry) the present
      study sought to identify the neurocognitive correlates of executive functions in
      individuals with Asperger syndrome (AS) compared to healthy controls. Results
      disclosed subtle group differences regarding response speed on only one CANTAB
      subtest that is thought to tap fronto-executive network functions (SWM/spatial
      working memory). Across all participants, SWM performance was significantly
      associated with two brain regions (precentral gyrus white matter, precuneus grey
      matter), thus suggesting a close link between fronto-executive functions (SWM)
      and circumscribed fronto-parietal brain structures. Finally, symptom severity
      (ADOS total score) was best predicted by response speed on a set-shifting task
      (IES) thought to tap fronto-striatal functions (corrected R2 56%).

PMID- 23117424
TI  - The broader autism phenotype in simplex and multiplex families.
AB  - Mothers, fathers, and siblings from 87 multiplex (M-mothers, M-fathers, and M
      siblings) and 41 simplex (S-mothers, S-fathers, and S-siblings) Autism spectrum
      disorder families were assessed using the Broader Phenotype Autism Symptom Scale.
      S-mothers, S-fathers, and S-siblings showed more social interest and were more
      expressive in their use of nonverbal communication compared to M-mothers, M
      fathers, and M-siblings. Conversational skills were also improved in S-fathers
      and S-siblings compared to M-fathers and M-siblings. S-siblings showed
      significantly lower rigidity and intense interests compared to M-siblings. The
      decreased number and intensity of broader autism phenotype traits observed in
      parents and siblings within simplex families provide behavioral evidence
      consistent with findings of increased de novo genetic events in simplex families.

PMID- 23117425
TI  - The Kabachnik-Fields reaction: mechanism and synthetic use.
AB  - The Kabachnik-Fields (phospha-Mannich) reaction involving the condensation of
      primary or secondary amines, oxo compounds (aldehydes and ketones) and >P(O)H
      species, especially dialkyl phosphites, represents a good choice for the
      synthesis of  alpha-aminophosphonates that are of significant importance due to
      their biological activity.  In general, these three-component reactions may take
      place via an imine or an  alpha-hydroxy-phosphonate intermediate. The monitoring
      of a few Kabachnik-Fields reactions by in situ Fourier transform IR spectroscopy
      has indicated the involvement of the imine intermediate that was also justified
      by theoretical calculations. The Kabachnik-Fields reaction was extended to >P(O)H
      species, comprising cyclic phosphites, acyclic and cyclic  H-phosphinates, as
      well as secondary phosphine oxides. On the other hand, heterocyclic amines were
      also used to prepare new alpha-amino phosphonic, phosphinic and phosphine oxide
      derivatives. In most cases, the synthesis under solvent-free microwave (MW)
      conditions is the method of choice. It was proved that, in the cases studied by
      us, there  was no need for the use of any catalyst. Moreover, it can be said that
      sophisticated  and environmentally unfriendly catalysts suggested are completely
      unnecessary under  MW conditions. Finally, the double Kabachnik-Fields reaction
      has made available bis(phosphonomethyl)amines, bis(phosphinoxidomethyl)amines and
      related species. The bis(phosphinoxidomethyl)amines serve as precursors for
      bisphosphines that furnish ring platinum complexes on reaction with
      dichlorodibenzonitriloplatinum.

PMID- 23117426
TI  - Purification and identification of antioxidant peptides from enzymatic
      hydrolysates of Tilapia (Oreochromis niloticus) frame protein.
AB  - Tilapia frame protein was hydrolyzed by different proteases, including properase
      E, pepsin, trypsin, flavourzyme, neutrase, gc106 and papain, to obtain
      antioxidant peptides. The tilapia frame protein hydrolysate (TFPH) obtained by
      trypsin exhibited the highest degree of hydrolysis and antioxidant activity.
      Three series of peptides (TFPH1, TFPH 2 and TFPH 3) were obtained by
      ultrafiltration of TFPH through molecular weight  cut-off membranes of 5, 3 and 1
      kDa, respectively, and their IC(50) values on scavenging 1,1-diphenyl-2
      picrylhydrazyl (DPPH) radical, superoxide anion radical (&#8226;O(2)), hydrogen
      peroxides (H(2)O(2)) and hydroxyl radical (&#8226;OH) activities were determined
      and compared with glutathione (GSH). The results showed that TFPH1 had the
      highest antioxidant activity. TFPH1 was further purified using ion exchange
      chromatography, gel filtration chromatography, and reversed phase high
      performance liquid chromatography (RP-HPLC). Finally, two antioxidant peptides
      were identified and the amino acid sequences were identified as Asp-Cys-Gly-Tyr
      (456.12 Da) and Asn-Tyr-Asp-Glu-Tyr (702.26 Da), respectively. The IC(50) values
      of two peptides on hydroxyl radical scavenging activity were 27.6 and 38.4
      &#956;g/mL, respectively.

PMID- 23117427
TI  - In vitro antioxidant effects of Aloe barbadensis Miller extracts and the
      potential role of these extracts as antidiabetic and antilipidemic agents on
      streptozotocin-induced type 2 diabetic model rats.
AB  - In this study, the total phenolic and flavonoid contents, the 2,2-diphenyl-1
      picryl hydrazyl (DPPH) radical scavenging ability and the ferric reducing power
      (FRAP) of  Aloe vera were measured to determine the antioxidant activity of this
      species. The in vivo antidiabetic effects of the plant were also investigated
      using streptozotocin-induced type 2 diabetic model rats that were divided into
      five groups based on the treatment received:  (1) water (WC); (2) glibenclamide;
      (3) concentrated gel extract (Gel-C); (4) ethanol (80%) gel extract (Gel-Et); and
      (5) ethanol (80%) skin extract of Aloe vera (Skin-Et). Skin-Et, which contained
      the highest level of total phenolics (62.37 &#177; 1.34 mg(gallic acid)/kg) and
      flavonoids (20.83 &#177; 0.77 mg/kg), exhibited the highest scavenging activity
      (85.01 &#177; 0.52%) and the greatest reducing power (185.98 &#177; 0.41
      &#181;M), indicating that the skin contained the highest level of antioxidants.
      The oral consumption of Gel-Et for 4 weeks a caused significant reduction in the
      fasting serum glucose levels of the rats. The rats in the Gel-C-, Gel-Et- and
      Skin-Et-treated groups experienced a reduction in their total cholesterol levels
      by 11%, 17% and 25%, respectively and a reduction in their LDL cholesterol levels
      by 45%, 3% and 69%, respectively. The in vivo experimental antioxidant parameter
      MDA is strongly correlated with the in vitro antioxidant parameters of flavonoids
      and polyphenols, namely the DPPH and FRAP values (r = 0.94, 0.92, 0.93, 0.90),
      thus confirming the antioxidant potential of the Aloe vera extracts.

PMID- 23117428
TI  - Hesperidin prevents retinal and plasma abnormalities in streptozotocin-induced
      diabetic rats.
AB  - Diabetic retinopathy is a complex disease that potentially involves increased
      production of advanced glycosylation end products (AGEs) and elevated aldose
      reductase (AR) activity, which are related with oxidative stress and
      inflammation. The aim of this study was to investigate the effects of hesperidin
      on retinal and plasma abnormalities in streptozotocin-induced diabetic rats.
      Hesperidin (100, 200 mg/kg daily) was given to diabetic rats for 12 weeks. The
      blood-retina breakdown (BRB) was determined after  2 weeks of treatment followed
      by the measurement of related physiological parameters with ELISA kits and
      immunohistochemistry staining at the end of the study. Elevated AR activity and
      blood glucose, increased retinal levels of vascular endothelial growth factor
      (VEGF), ICAM-1, TNF-&#945;, IL-1&#946; and AGEs as well as reduced retina
      thickness were observed in diabetic rats. Hesperidin treatment
      signi&#64257;cantly suppressed BRB breakdown and increased retina thickness,
      reduced blood glucose, AR activity and retinal TNF-&#945;, ICAM-1, VEGF, IL
      1&#946; and AGEs levels. Furthermore, treatment with hesperidin
      signi&#64257;cantly reduced plasma malondialdehyde (MDA) levels and increased SOD
      activity in diabetic rats. These data demonstrated that hesperidin attenuates
      retina and plasma abnormalities via anti-angiogenic, anti-inflammatory and
      antioxidative effects, as well as the inhibitory effect on polyol pathway and
      AGEs accumulation.

PMID- 23117429
TI  - Solvent-free synthesis, DNA-topoisomerase II activity and molecular docking study
      of new asymmetrically N,N'-substituted ureas.
AB  - A new series of asymmetrically N,N'-substituted ureas 20&#8211;25 was prepared
      using solvent free conditions, which is an eco-friendly methodology, starting
      with Schiff bases derived from cinnamaldehyde and p-substituted anilines, which
      are subsequently submitted to reduction reactions that afford the corresponding
      asymmetric secondary amines. All of the intermediates were prepared using solvent
      free reactions, which were compared to traditional methodologies. All of the
      reactions required a remarkably short amount of time and provided good yields
      when solvent free conditions were employed compared to other methodologies. The
      DNA-topoisomerase II-&#945; (topo II-&#945;) activity was evaluated in relaxation
      assays, which showed that all of the compounds inhibited the enzyme activity at
      10 &#956;M, except for urea 24. Furthermore, a molecular docking study indicated
      that the compounds 20&#8211;25 binding to the topo II-&#945; are able to interact
      with the same binding site as the anticancer drug etoposide, suggesting that the
      ureas could inhibit the enzyme by the same mechanism of action observed for
      etoposide, which prevents  re-ligation of the DNA strands.

PMID- 23117430
TI  - Secondary metabolites from two species of Tolpis and their biological activities.
AB  - Phytochemical research of two Tolpis species, T. proustii and T. lagopoda, led to
      the isolation of three new compounds: 30-chloro-3&#946;-acetoxy-22&#945;-hydroxyl
      20(21)-taraxastene (1), 3&#946;,22&#945;-diacetoxy-30-ethoxy-20(21)-taraxastene
      (2) and 3&#946;,28-dihydroxy-11&#945;-hydroperoxy-12-ursene (3). The structures
      of the new compounds were elucidated by means of extensive IR, NMR, and MS data
      and by comparison of data reported in the literature. The in vitro antioxidant
      activities of the extracts were assessed by the DPPH and ABTS scavenging methods.
      The cytotoxicity of several known compounds and its derivatives was also assessed
      against human myeloid leukemia K-562 and K-562/ADR  cell lines.

PMID- 23117431
TI  - Quantitative studies on structure-DPPH* scavenging activity relationships of food
      phenolic acids.
AB  - Phenolic acids are potent antioxidants, yet the quantitative structure-activity
      relationships of phenolic acids remain unclear. The purpose of this study was to
      establish 3D-QSAR models able to predict phenolic acids with high DPPH*
      scavenging activity and understand their structure-activity relationships. The
      model has been established by using a training set of compounds with cross
      validated q2 = 0.638/0.855, non-cross-validated  r2 = 0.984/0.986, standard error
      of estimate = 0.236/0.216, and F = 139.126/208.320 for the best CoMFA/CoMSIA
      models. The predictive ability of the models was validated with the correlation
      coefficient r2(pred) = 0.971/0.996 (>0.6) for each model. Additionally, the
      contour map results suggested that structural characteristics of phenolics acids
      favorable for the high DPPH* scavenging activity might include: (1) bulky and/or
      electron-donating substituent groups on the phenol ring; (2) electron-donating
      groups at the meta-position and/or hydrophobic groups at the meta-/ortho
      position; (3) hydrogen-bond donor/electron-donating groups at the ortho-position.
      The results have been confirmed based on structural analyses of phenolic acids
      and their DPPH* scavenging data from eight recent publications. The findings may
      provide deeper insight into the antioxidant mechanisms and provide useful
      information for selecting phenolic acids for free radical scavenging properties.

PMID- 23117432
TI  - Comparative analysis of the main bioactive components of San-ao decoction and its
      series of formulations.
AB  - A high performance liquid chromatographic (HPLC) method with diode array
      detection (DAD) was established for simultaneous determination of seven main
      bioactive components in San-ao decoction and its series of formulae (San-ao
      decoction, Wu-ao decoction, Qi-ao decoction and Jia-wei San-ao decoction). Seven
      compounds were analyzed simultaneously with a XTerra C(18) column (4.6 mm &#215;
      250 mm, 5 &#181;m) using a linear gradient elution of a mobile phase containing
      acetonitrile (A) and a buffer solution (0.02 mol/L potassium dihydrogen phosphate
      and adjusted to pH 3 using phosphoric acid) (B); the flow rate was 1.0 mL/min.
      The sample was detected with DAD at 210, 254 and 360 nm and the column was
      maintained at 30 &#176;C. All the compounds showed good linearity (r2 > 0.9984)
      in the tested concentration range. The precisions were evaluated by intra-day and
      inter-day tests, and relative standard deviation (R.S.D.) values within the range
      of 0.83%&#8211;2.53% and 0.64%&#8211;2.77% were reported, respectively. The
      recoveries of the quantified compounds were observed to cover a range from 95.34%
      and 104.82% with R.S.D. values less than 2.72%. The validated method was
      successfully applied for the simultaneous determination of seven main bioactive
      components including ephedrine (1), amygdalin (2), liquiritin (3), benzoic acid
      (4), isoliquiritin (5), formononetin (6) and glycyrrhizic acid (7) in San-ao
      decoction and its series of formulae. The results also showed a wide variation in
      the content of the identified active compounds in these samples, which could also
      be helpful to illustrate the drug interactions after some herbs combined in
      different formulations.

PMID- 23117433
TI  - The effects of Davallic acid from Davallia divaricata Blume on apoptosis
      induction in A549 lung cancer cells.
AB  - Traditional or folk medicinal herbs continue to be prescribed in the treatment of
      various diseases and conditions in many cultures. Recent scientific efforts have
      focused on the potential roles of extracts of traditional herbs as alternative
      and complementary medications for cancer treatment. In Taiwan, Davallia
      divaricata Blume has been traditionally employed in folk medicine for therapy of
      lung cancer, davallic acid being the major active compound of D. divaricata
      Blume. In this study, we investigated the inhibitory activity of davallic acid on
      the proliferation of A549 lung cancer cells. Davallic acid was extracted from D.
      divaricata Blume, and its effects on cell viability, cell cycle distribution, ROS
      level, and apoptotic protein expression in A549 cells were determined. Davallic
      acid significantly induced reactive oxygen species (ROS) generation as well as
      caspase-3, -8, and -9 activation, thereby repressing A549 cell growth and
      elevating apoptotic activity. Since lung cancer has a high incidence of
      recurrence, these results indicate that davallic acid may have the potential to
      be a natural anti-lung cancer compound, and may provide a basis for further study
      of its use in combating cancer.

PMID- 23117434
TI  - Antibacterial, antifungal and cytotoxic isoquinoline alkaloids from Litsea
      cubeba.
AB  - Five novel isoquinoline alkaloids (+)-N-(methoxylcarbonyl)-N-nordicentrin (1),
      (+)-N-(methoxylcarbonyl)-N-norpredicentrine (2), (+)-N-(methoxylcarbonyl)-N
      norbulbodione (3), and (+)-N-(methoxylcarbonyl)-N-norisocorydione (4), and (+)-8
      methoxyisolaurenine-N- oxide (5) were isolated, together with one known compound,
      (+)-N-(methoxylcarbonyl)- N-norglaucine (6), from a 70% EtOH extract of the barks
      of Litsea cubeba. Structural elucidation of all the compounds were performed by
      spectral methods such as 1D- and 2D-NMR, IR, UV, and HRESIMS. Alkaloids 1, 2 and
      6 showed antimicrobial activity against the bacterium S. aureus and two fungi (A.
      alternata and C. nicotianae). Compounds 3,4 exhibited significant cytotoxicity
      against all of six tested tumor cell lines.

PMID- 23117435
TI  - 4-(1H-Pyrazol-1-yl) benzenesulfonamide derivatives: identifying new active
      antileishmanial structures for use against a neglected disease.
AB  - Leishmaniasis is a neglected disease responsible for about 56,000 deaths every
      year. Despite its importance, there are no effective, safe and proper treatments
      for leishmaniasis due to strain resistance and/or drug side-effects. In this work
      we report the synthesis, molecular modeling, cytotoxicity and the antileishmanial
      profile of a series of  4-(1H-pyrazol-1-yl)benzenesulfonamides. Our experimental
      data showed an active profile for some compounds against Leishmania infantum and
      Leishmania amazonensis. The profile of two compounds against L. infantum was
      similar to that of pentamidine, but with lower cytotoxicity. Molecular modeling
      evaluation indicated that changes in electronic regions, orientation as well as
      lipophilicity of the derivatives were areas to improve the interaction with the
      parasitic target. Overall the compounds represent feasible prototypes for
      designing new molecules against L. infantum and L. amazonensis.

PMID- 23117436
TI  - Evaluation of deoxyribonucleic acid toxicity induced by the radiopharmaceutical
      99mTechnetium-Methylenediphosphonic acid and by stannous chloride in Wistar rats.
AB  - Radiopharmaceuticals are employed in patient diagnostics and disease treatments.
      Concerning the diagnosis aspect, technetium-99m (99mTc) is utilized to label
      radiopharmaceuticals for single photon computed emission tomography (SPECT) due
      to its physical and chemical characteristics. 99mTc fixation on pharmaceuticals
      depends on a reducing agent, stannous chloride (SnCl(2)) being the most widely
      utilized. The genotoxic, clastogenic and anegenic properties of the 99mTc
      MDP(methylene diphosphonate used for bone SPECT) and SnCl(2) were evaluated in
      Wistar rat blood cells using the Comet assay and micronucleus test. The
      experimental approach was to endovenously administer NaCl 0.9% (negative
      control), cyclophosphamide 50 mg/kg b.w. (positive control), SnCl(2) 500
      &#956;g/mL or 99mTc-MDP to animals and blood samples taken immediately before the
      injection, 3, and 24 h after (in the Comet assay) and 36 h after, for
      micronucleus test. The data showed that both SnCl(2) and 99mTc-MDP-induced
      deoxyribonucleic acid (DNA) strand breaks in rat  total blood cells, suggesting
      genotoxic potential. The 99mTc-MDP was not able to  induce a significant DNA
      strand breaks increase in in vivo assays. Taken together, the  data presented
      here points to the formation of a complex between SnCl(2) in the
      radiopharmaceutical 99mTc-MDP, responsible for the decrease in cell damage,
      compared to both isolated chemical agents. These findings are important for the
      practice of  nuclear medicine.

PMID- 23117437
TI  - Enhancement of epimedium fried with suet oil based on in vivo formation of self
      assembled flavonoid compound nanomicelles.
AB  - The purpose of this work was to research the enhancement of Epimedium fried with
      suet oil based on the in vivo formation self-assembled flavonoid nanomicelles.
      Taking icariin as the representative, under the action of suet oil, self
      assembled nanomicelles were prepared under simulated gastrointestinal tract
      conditions and were characterized by dynamic light scattering and transmission
      electron microscopy (TEM). The experiments with icariin self-assembled
      nanomicelles without suet oil were done according to the above. The influence of
      suet oil on the transportation of icariin across Caco-2 cell monolayers and the
      absorption in rat intestine of self-assembled nanomicelles were evaluated. The
      particle size of icariin self-assembled nanomicelles with suet oil was smaller
      than without suet oil. The nanomicelles seemed to be monodisperse spherical
      particle with smooth surfaces. The icariin entrapment efficiency of self
      assembled nanomicelles with suet oil was increased from 43.1% to 89.7%. In Caco-2
      cell monolayers, the absorptive permeability, secretory permeability and efflux
      ratio of icariin self-assembled nanomicelles with suet oil was  1.26 &#215;
      10&#8722;6 cm/s, 5.91 &#215; 10&#8722;6 cm/s and 4.69, respectively, while that
      of icariin self-assembled nanomicelles without suet oil was 0.62 &#215;
      10&#8722;6 cm/s, 3.00 &#215; 10&#8722;6 cm/s, and 4.84, respectively. In rat
      intestinal perfusion experiments, the permeability coefficient of icariin self
      assembled nanomicelles with suet oil in duodenum was higher than the value of
      icariin self-assembled nanomicelles without suet oil (p < 0.05). With the action
      of suet oil, icariin self-assembled nanomicelles were more stable and the
      entrapment efficiency was higher than that without suet oil, which could increase
      the solubility of icariin and improve its intestinal absorption. Therefore, suet
      oil plays a role in its enhancement.

PMID- 23117438
TI  - Quercetin improves baroreflex sensitivity in spontaneously hypertensive rats.
AB  - Quercetin is a well-known antioxidant. Here, we investigated the effects of
      treatment with quercetin on mean arterial pressure (MAP), heart rate (HR) and
      baroreflex sensitivity (BRS) in spontaneously hypertensive rats (SHR). SHR and
      their controls (WKY) were orally treated with quercetin (2, 10 or 25 mg/kg/day)
      or saline for seven days. On the 8th day, MAP and HR were recorded. BRS was
      tested using phenylephrine (8 mg/kg, i.v.) and sodium nitroprusside (25 mg/kg,
      i.v.). Oxidative stress was measured by tiobarbituric acid reactive species
      assay. The doses of 10 (n = 8) and 25 mg/kg (n = 8) were able to decrease the MAP
      in SHR (n = 9) (163 &#177; 4 and 156 &#177; 5 vs. 173 &#177; 6, respectively, p <
      0.05) but not in WKY (117 &#177; 1 and 118 &#177; 2 vs. 113 &#177; 1,
      respectively, p < 0.05). The dose of 25 mg/kg/day increased the sensitivity of
      parasympathetic component of the baroreflex (&#8722;2.47 &#177; 0.31 vs.
      &#8722;1.25 &#177; 0.8 bpm/mmHg) and decreased serum oxidative stress in SHR
      (2.04 &#177; 0.17 vs. 3.22 &#177; 0.37 nmol/mL, n = 6). Our data suggest that
      treatment with quercetin reduces hypertension and improves BRS in SHR via
      reduction in oxidative stress.

PMID- 23117439
TI  - Action of natural products on p2 receptors:  a reinvented era for drug discovery.
AB  - Natural products contribute significantly to available drug therapies and have
      been a rich source for scientific investigation. In general, due to their low
      cost and traditional use in some cultures, they are an object of growing interest
      as alternatives to synthetic drugs. With several diseases such as cancer, and
      inflammatory and neuropathic diseases having been linked to the participation of
      purinergic (P2) receptors, there has been a flurry of investigations on ligands
      within natural products. Thirty-four different sources of these compounds have
      been found so far, that have shown either agonistic or antagonistic effects on P2
      receptors. Of those, nine different plant sources demonstrated effects on P2X2,
      P2X3, P2X7, and possibly P2Y12 receptor subtypes. Microorganisms, which represent
      the largest group, with 26 different sources, showed effects on both receptor
      subtypes, ranging from P2X1 to P2X4 and P2X7, and P2Y1, P2Y2, P2Y4, and P2Y6. In
      addition, there were seventeen animal sources that affected P2X7 and P2Y1 and
      P2Y12 receptors. Natural products have provided some fascinating new mechanisms
      and sources to better understand the P2 receptor antagonism. Moreover, current
      investigations should clarify further pharmacological mechanisms in order to
      consider these products as potential new medicines.

PMID- 23117440
TI  - Limonoids and their anti-proliferative and anti-aromatase properties in human
      breast cancer cells.
AB  - Lemons are a widely used citrus crop and have shown several potential health
      benefits. In the present study, the mechanism and effectiveness of the anti
      cancer and anti-aromatase properties of limonoids were investigated for the first
      time. Defatted lemon (Citrus lemon L. Burm) seed powder was extracted with ethyl
      acetate (EtOAc) and methanol (MeOH) for 16 h each, successively. These extracts
      were fractionated using 1D (silica) and 2D (ion exchange and SP-70 columns)
      column chromatography to obtain nine limonoids. The compounds were identified by
      TLC, HPLC, and LC-MS techniques. A panel of 9 purified limonoids, including
      limonin, nomilin, obacunone, limonexic acid (LNA), isolimonexic acid (ILNA),
      nomilinic acid glucoside (NAG), deacetyl nomilinic acid glucoside (DNAG), limonin
      glucoside (LG) and obacunone glucoside (OG) as well as 4 modified compounds such
      as limonin methoxime (LM), limonin oxime (LO), defuran limonin (DL), and defuran
      nomilin (DN), were screened for their cytotoxicity on estrogen receptor (ER)
      positive (MCF-7) or ER-negative (MDA-MB-231) human breast cancer cells. We
      further tested the mechanism of the anti-proliferative activity of limonoids
      using an in vitro aromatase enzyme assay and western blot with anti-caspase-7.
      Among the tested limonoids, 11 limonoids exhibited cytotoxicity on MCF-7 whereas
      8 limonoids showed cytotoxicity against the MDA-MB-231 cell lines. Although most
      of the limonoids showed anti-aromatase activity, the inhibition of proliferation
      was not related to the anti-aromatase activity. On the other hand, the anti
      proliferative activity was significantly correlated with caspase-7 activation by
      limonoids. Our findings indicated that the citrus limonoids may have potential
      for the prevention of estrogen-responsive breast cancer (MCF-7) via caspase-7
      dependent pathways.

PMID- 23117441
TI  - Synthesis of pyrazolo[5,1-a]isoquinolines via silver(I)-rhodium(I) cooperative
      catalysis in the reaction of N'-(2-alkynylbenzylidene)hydrazide with cycloprop-2
      ene-1,1-dicarboxylate.
AB  - A tandem reaction between N'-(2-alkynylbenzylidene)hydrazide and cycloprop-2-ene
      1,1-dicarboxylate co-catalyzed by silver triflate and
      tris(triphenylphosphine)rhodium chloride is reported. The reaction proceeds
      through 6-endo-cyclization, [3 + 2] cycloaddition, cyclopropane opening, and
      aromatization, leading to pyrazolo[5,1-a]isoquinolines in moderate to good
      yields.

PMID- 23117442
TI  - Incidence of severe asthmatic reactions after challenge exposure to occupational
      agents.
AB  - BACKGROUND: Specific inhalation challenges (SICs) with occupational agents are
      used to establish the diagnosis and etiology of occupational asthma. The aim of
      this study was to assess the frequency and determinants of severe asthmatic
      reactions induced by various occupational agents during SICs performed using
      realistic methods of exposure. METHODS: The SIC records of 335 consecutive
      subjects with a positive SIC (ie, >= 20% fall in FEV1) due to various
      occupational agents were reviewed. Asthmatic reactions were graded as moderate
      when requiring repeated administration of an inhaled short-acting beta2-agonist
      (SABA) and severe when requiring repeated SABA and systemic corticosteroids.
      RESULTS: Overall, 68 of the 335 subjects (20%) required an inhaled SABA during
      the SICs. The multivariate logistic regression analysis showed that the need for
      an inhaled SABA increased when the SIC involved a low-molecular-weight agent
      (LMW) (OR, 2.47; 95% CI, 1.43-4.28) and marginally so when the subjects required
      regular treatment with an inhaled corticosteroid (OR, 1.62; 95% CI, 0.93-2.80).
      The severity of asthmatic reactions was graded as moderate in 12% and severe in
      3% of the subjects. Of the 10 severe reactions, five developed after exposures <=
      5 min. Multivariate logistic regression analysis showed that challenging subjects
      with a LMW agent was the only significant determinant for the development of
      moderate/severe reactions (OR, 3.05; 95% CI, 1.62-5.73). CONCLUSIONS: Challenges
      with LMW agents are associated with a higher risk of an asthmatic reaction
      requiring pharmacologic treatment. This study may provide useful guidelines for
      further improving the safety of SICs.

PMID- 23117443
TI  - Telephone monitoring and support after discharge from residential PTSD treatment:
      a randomized controlled trial.
AB  - OBJECTIVE: This study assessed whether adding a telephone care management
      protocol to usual aftercare improved the outcomes of veterans in the year after
      they were discharged from residential treatment for posttraumatic stress disorder
      (PTSD). METHODS: In a multisite randomized controlled trial, 837 veterans
      entering residential PTSD treatment were assigned to receive either standard
      outpatient aftercare (N=425) or standard aftercare plus biweekly telephone
      monitoring and support (N=412) for three months after discharge. Symptoms of PTSD
      and depression, violence, substance use, and quality of life were assessed by
      self-report questionnaires at intake, discharge, and four and 12 months
      postdischarge. Treatment utilization was determined from the Department of
      Veterans Affairs administrative data. RESULTS: Telephone case monitors reached
      355 participants (86%) by phone at least once and provided an average of 4.5 of
      the six calls planned. Participants in the telephone care and treatment-as-usual
      groups showed similar outcomes on all clinical measures. Time to
      rehospitalization did not differ by condition. In contrast with prior studies
      reporting poor treatment attendance among veterans, participants in both
      telephone monitoring and treatment as usual completed a mental health visit an
      average of once every ten days in the year after discharge. Many participants had
      continuing problems despite high utilization of outpatient care. CONCLUSIONS:
      Telephone care management had little incremental value for patients who were
      already high utilizers of mental health services. Telephone care management could
      potentially be beneficial in settings where patients experience greater barriers
      to engaging with outpatient mental health care after discharge from inpatient
      treatment.

PMID- 23117444
TI  - Effects of elevated perfusion pressure and pulsatile flow on human saphenous
      veins isolated from diabetic and non-diabetic patients.
AB  - OBJECTIVE: This study was carried out to determine high pressure and pulsatile
      flow perfusion effects on human saphenous vein (HSV) segments obtained from
      diabetic and non-diabetic patients. METHODS: The veins were perfused with
      oxygenated Krebs solution for 3 h, with a pulsatile flow rate of 100 mL/min and
      pressures of 250 * 200 or 300 * 250 mmHg. After perfusion, veins were studied by
      light microscopy; nitric oxide synthase (NOS) isoforms, CD34 and nitrotyrosine
      immunohistochemistry and tissue nitrite/nitrate (NO(x)) and malondialdehyde (MDA)
      quantification. RESULTS: Light microscopy revealed endothelial denuding areas in
      all HSV segments subjected to 300 * 250 mmHg perfusion pressure, but the luminal
      area was similar. The percentage of luminal perimeter covered by endothelium
      decreased as perfusion pressures increased, and significant differences were
      observed between groups. The endothelial nitric oxide synthase (eNOS) isoform
      immunostaining decreased significantly in diabetic patients' veins independent of
      the perfusion pressure levels. The inducible NOS (iNOS), neuronal NOS (nNOS) and
      nitrotyrosine immunostaining were similar. Significant CD34 differences were
      observed between the diabetic 300 * 250 mmHg perfusion pressure group and the non
      diabetic control group. Tissue nitrite/nitrate and MDA were not different among
      groups. CONCLUSIONS: Pulsatile flow and elevated pressures for 3 h caused
      morphological changes and decreased the eNOS expression in the diabetic patients'
      veins.

PMID- 23117445
TI  - Indirubin-3'-oxime induces mitochondrial dysfunction and triggers growth
      inhibition and cell cycle arrest in human neuroblastoma cells.
AB  - Neuroblastoma is the most common extracranial solid tumor found in infancy and
      childhood. Current multimodal therapies such as surgery, chemotherapy,
      radiotherapy and stem cell transplantation often cause inevitable severe side
      effects, therefore, it is necessary to develop novel drugs with higher efficacy
      on neuroblastoma cells and minimal side-effects on normal cells. Indirubin-3'
      oxime (I3M), an indigo alkaloid, was found to exhibit potent antitumor activities
      on various types of cancer cells. However, its modulatory effects on human
      neuroblastoma and the underlying mechanisms remain poorly understood. As
      mitochondrial biogenesis and function play critical roles in cell growth and
      survival, in the present study the effects of I3M on mitochondrial functions and
      their correlation to the anticancer effect of I3M on human neuroblastoma cells
      were investigated. I3M was found to inhibit the growth of the human neuroblastoma
      LA-N-1, SH-SY5Y and SK-N-DZ cells in a dose- and time-dependent manner, but
      exhibited little, if any, direct cytotoxicity on normal cells. Mechanistic
      studies showed that I3M specifically decreased the expression of the
      mitochondrial regulators ERRgamma and PGC-1beta and resulted in decreased
      mitochondrial mass and altered mitochondrial function characterized by a
      reduction in mitochondrial membrane potential and elevation of reactive oxygen
      species levels in LA-N-1 cells. I3M also increased the level of CDK inhibitor
      p27Kip1 and reduced the levels of CDK2 and cyclin E in LA-N-1 cells, leading to
      cell cycle arrest at the G0/G1 phase. Collectively, these results suggest that
      mitochondrial dysfunction might be an important mechanism underlying the I3M
      induced cell cycle arrest.

PMID- 23117446
TI  - Salinicola zeshunii sp. nov., a moderately halophilic bacterium isolated from
      soil of a chicken farm.
AB  - The taxonomic status of a moderately halophilic bacterium, strain N4(T), isolated
      from soil of a chicken farm in China was determined. It was Gram-negative, non
      spore-forming, motile, and rod-shaped. Phylogenetic analysis based on 16S rRNA
      gene sequence indicated that this strain belonged to the genus Salinicola, as it
      showed the highest sequence similarities to Salinicola salaries M27(T) (98.3 %),
      Salinicola socius SMB35(T) (98.1 %), and Salinicola halophilus CG4.1(T) (98.1 %).
      The major cellular fatty acids were C(16:0) (25.6 %), C(18:1)omega7c (35.0 %),
      and C(19:0) cyclo omega8c (11.9 %), which are properties shared by members of the
      genus Salinicola. The DNA G+C content of strain N4(T) was 69.1 mol %. The level
      of DNA-DNA relatedness between strain N4(T) and the other three type strains of
      the genus of Salinicola salaries M27(T), Salinicola socius SMB35(T), and
      Salinicola halophilus CG4.1(T) were 34.3, 28.7, and 26.9 %, respectively. Based
      on the results of phenotypic, chemotaxonomic, DNA-DNA relatedness, and
      phylogenetic analysis, strain N4(T) should be classified as a novel species of
      the genus Salinicola, for which the name Salinicola zeshunii sp. nov. is
      proposed, with strain N4(T) (=KACC 16602(T) = CCTCC AB 2012912(T)) as the type
      strain.

PMID- 23117447
TI  - Surgical telementoring in knowledge translation--clinical outcomes and
      educational benefits: a comprehensive review.
AB  - BACKGROUND: Surgical telementoring has been reported for decades. However, there
      exists limited evidence of clinical outcome and educational benefits. OBJECTIVE:
      To perform a comprehensive review of surgical telementoring surveys published in
      the past 2 decades. RESULTS: Of 624 primary identified articles, 34 articles were
      reviewed. A total of 433 surgical procedures were performed by 180 surgeons. Most
      common telementored procedures were laparoscopic cholecystectomy (57 cases, 13%),
      endovascular treatment of aortic aneurysm (48 cases, 11%), laparoscopic colectomy
      (32 cases, 7%), and nefrectomies (41 cases, 9%). In all, 167 (38%) cases had a
      laparoscopic approach, and 8 cases (5%) were converted to open surgery. Overall,
      20 complications (5%) were reported (liver bleeding, trocar port bleeding, bile
      collection, postoperative ileus, wound infection, serosa tears, iliac artery
      rupture, conversion open surgery). Eight surveys (23%) have structured assessment
      of educational outcomes. Telementoring was combined with simulators (n = 2) and
      robotics (n = 3). Twelve surveys (35%) were intercontinental. Technology
      satisfaction was high among 83% of surgeons. CONCLUSION: Few surveys have a
      structured assessment of educational outcome. Telementoring has improved impact
      on surgical education. Reported complication rate was 5%.

PMID- 23117448
TI  - [Construction of TDRG1 shRNA expression vector and interfering effect of TDRG1
      shRNA expression vector on NTERA-2 cells].
AB  - OBJECTIVE: To construct short hairpin RNA interfering expression vector of
      TDRG1,and detect the specific interfering effect of TDRG1-shRNA expression vector
      on NTERA-2 cells. METHODS: Oligos for short hairpin RNA targefing for TDRG1 were
      designed and connected to the expression vector pGPU6/GFP/Neo to construct the
      TDRG1 shRNA expression vector. The recombinant plasmid TDRG1-shRNA486, TDRG1
      shRNA738, TDRG1-shRNA921 and lipofectamine TM2000 were used to generate and
      transfect shRNA into NTERA-2 cells. Expression of TDRG1 mRNA was assayed by RT
      PCR. RESULTS: TDRG1-shRNA expression vector was successfully constructed. TDRG1
      shRNA486 was more effective in the suppression of TDRG1 with significant
      reduction of TDRG1 mRNA. CONCLUSION: TDRG1-shRNA can interfere the expression of
      TDRG1 in NTERA-2 cells.

PMID- 23117449
TI  - [Clinical application of the 3-dimensional speckle tracking imaging in coronary
      artery disease].
AB  - OBJECTIVE: To observe the 3-dimensional speckle tracking imaging (3D-STI) in
      clinical diagnosis of coronary artery disease by quantitatively evaluating left
      ventricular segmental and global systolic function. METHODS: According to the
      selective coronary artery angiography, 150 inpatients suspected of coronary
      artery disease were divided into 5 groups according to the distribution of the
      affected coronary arteries: a left anterior descending coronary artery group
      (LAD, n=46), a left circumflex coronary artery group (LCX, n=25), a right
      coronary artery group (RCA, n=23), a multivessel group (n=26), and a normal group
      (n=30). Gensini score was calculated according to coronary artery angiography.
      Conventional echocardiography was applied in each patient and wall motion score
      index (WMSI) was calculated. 3D-STI was applied in each patient to evaluate the
      segmental and global systolic function in the left ventricle. RESULTS: Compared
      with the normal group, ejection fraction was decreased in the multi-vessel group
      alone (P<0.05). Peak systolic 3D strains in all segments were decreased in the
      multi-vessel group (P<0.01), while peak systolic 3D strains in the main blood
      supply segments were decreased significantly in the rest of the groups (P<0.05).
      Global 3-dimensional strain (G3DS) was negatively correlated with Gensini score
      in patients with coronary artery disease (r= -0.76, P<0.01). Receiver operating
      characteristic curve analysis demonstrated that G3DS was more sensitive and
      accurate in clinical diagnosis of coronary artery disease. CONCLUSION: 3D-STI can
      quantitatively evaluate the segmental and global systolic function of the left
      ventricle, and reflect the extent of coronary artery stenosis in patients with
      coronary artery disease.

PMID- 23117450
TI  - [Detection of chromosomal aberrations in multiple myeloma with fluorescence in
      situ hybridization].
AB  - OBJECTIVE: To detect of chromosomal abnormalities in multiple myeloma (MM)
      patients with fluorescence in situ hybridization (FISH). METHODS: FISH was
      performed in 20 MM patients using 5 specific DNA probes. The difference in
      chromosomal abnormalities was compared by FISH and other routine cytogenetic
      tests. RESULTS: Eighteen of the 20 patients showed chromosomal abnormalities
      (90%). The positive rates of t(14q32), del(13q14), dup(1q21), and p53 gene were
      65% (13 in 20), 55% (11 in 20), 25% (5 in 20), and 15%(3 in 20), respectively.
      The abnormal rate of the conventional chromosome examination was 15% only.
      CONCLUSION: FISH is more sensitive than traditional chromosomal tests and can be
      used as an index in prognostic evaluation for MM. Del(13q14) and t(14q32) are the
      most common chromosomal abnormalities in MM patients.

PMID- 23117451
TI  - [Clinical features of 50 cases of primary gastric lymphoma].
AB  - OBJECTIVE: To analyze the clinical characteristics of primary gastric lymphoma
      (PGL) and to improve its diagnosis and treatment. METHODS: The clinical
      manifestations, diagnosis, treatments and history of 50 PGL patients, who were
      hospitalized from September 2005 to September 2009, were reviewed and analyzed.
      RESULTS: The main manifestation of PGL was epigastric pain with infrequent
      systemic symptoms, such as stomach ache, abdominal discomfort, vomit, black
      stool, loss of appetite, fever, feeble, and skinny. Pathological examination
      indicated that only 1 patient had T cell lymphoma while the rest 49 had B cell
      lymphoma. Fourteen had mucosa-associated lymphoid tissue lymphoma (MALT), 35 had
      diffuse large B cell lymphoma (DLBCL), and 2 had both DLBCL and MALT (DLBCML).
      All the 50 patients received chemotherapy, and 12 underwent surgical treatment
      besides chemotherapy. Fourteen out of the 49 patients with B cell lymphoma
      received rituximab together with chemotherapy, and 35 received chemotherapy
      alone. The 2-year survival rate in the patients receiving rituximab together with
      chemotherapy was higher than that in the patients receiving chemotherapy alone
      (85.7% vs 77.1%, P< 0.05). The 2-year survival rate in patients of clinical stage
      I-II was higher than that in patients of clinical stage III-IV (90.9% vs 71.4%,
      P< 0.05). CONCLUSION: The main clinical manifestation of PGL patients is non
      specific gastrointestinal symptoms, among which abdominal pain is most common.
      The clinical examination mainly relies on pathological examinations, and the most
      common pathological type of primary gastric lymphoma is DLBCL. The main treatment
      is chemotherapy, and the prognosis is related to the clinical stage and the use
      of rituximab. After the treatment, the 2-year survival rate in the 50 patients
      reaches 80.0%.

PMID- 23117452
TI  - [Effect of calcium ionophore A23187 plus IFN-gamma on dendritic cells derived
      from peripheral blood mononuclear cells].
AB  - OBJECTIVE: To explore the effect of calcium ionophore (CI) A23187 plus IFN-gamma
      on dendritic cells (DC) from healthy human peripheral blood mononuclear cells
      (PBMNC). METHODS: PBMNC from healthy donors were treated with GM-CSF plus IL-4,
      A23187, and A23187 plus IFN-gamma, respectively. After culture for 72 h, the
      change of cellular morphology was observed under light microscope and electron
      microscope. Surface markers on DC were analyzed by flow cytometry. MTT
      colorimetry was used to detect the proliferation of allogeneic T cells. Plasma
      concentrations of IL-12 and IFN-gamma were measured by ELISA. RESULTS: PBMNC
      treated with A23187 plus IFN-gamma for 72 h presented DC with typical morphology
      effectively. The surface markers CD40, CD83, and CD86 were obviously increased in
      group A23187 plus IFN-gamma (P<0.01), but decreased in CD1a (P<0.01). In
      addition, it evidently stimulated the proliferation of allogeneic T cells. The
      levels of IL-12 and IFN-gamma were significantly increased compared with other
      groups (P<0.01). CONCLUSION: A23187 plus IFN-gamma can effectively enhance marked
      transformation of PBMNC into DC.

PMID- 23117453
TI  - [Dynamic expression of E2F1 in lung of premature rats with hyperoxia-induced
      chronic lung disease and its significance].
AB  - OBJECTIVE: To determine the dynamic expression of E2F1 in lung of premature rats
      with hyperoxia-induced chronic lung disease and the relation between E2F1 and
      pulmonary fibrosis. METHODS: Premature Wistar rats at 21 days gestation were
      randomly and equally divided into a hyperoxia group and a room air group. The
      hyperoxia group was continuously exposed to hyperoxia (90%) while the air group
      in room air. Lung tissues in the 2 groups were obtained at 3, 7 and 14 days after
      exposing to either room air or hyperoxia. The changes of pulmonary histopathology
      at different time points were observed by hematoxylin and eosin staining; the
      severity of pulmonary fibrosis was evaluated; and the expression of E2F1 in lung
      tissue was detected by immunohistochemistry and Western blot. RESULTS: After 3
      days of hyperoxia, no significant interstitial fibrosis was observed; while after
      7 days in the hyperoxia group, interstitial fibrosis was observed. These changes
      became more obvious after 14 days of prolonged hyperoxia exposure. No significant
      difference in the expressions of E2F1 protein was found between the hyperoxia
      group and the room air group 3 days postnatally (P>0.05). The expression of E2F1
      in the hyperoxia group significantly increased 7 days and 14 days postnatally
      (P<0.05, P<0.01). CONCLUSION: Abnormality of E2F1 expression is involved in the
      pathological process of the proliferation of lung fibroblasts in hyperoxia
      induced chronic lung disease neonatal rats, and it plays an important role in
      lung fibrosis.

PMID- 23117454
TI  - [Changes of TGF-beta1 and CTGF in rats with increased blood flow-induced
      pulmonary artery hypertension].
AB  - OBJECTIVE: To evaluate the role of transforming growth factor-beta1 (TGF-beta1)
      and connective tissue growth factor (CTGF) in the pathogenesis of pulmonary
      artery hypertension, we observed the dynamic expression of TGF-beta1 and CTGF in
      rats with high blood flow. METHODS: Fifty adult male SD rats were randomly
      divided into 5 groups: a sham group (group S) and groups with right pneumonectomy
      for 1, 2, 4 and 6 weeks (PE1, PE2, PE4 and PE6 group), 10 rats per group. The
      mean pulmonary arterial pressure (mPAP), vessel morphometry and right ventricle
      hypertrophy index (RVHI) were measured. TGF-beta1 and CTGF protein expression in
      the lung tissues were determined with immunohistochemistry and Western blot. The
      expression of TGF-beta1 mRNA and CTGF mRNA in the lung tissues was evaluated by
      RT-PCR. RESULTS: Compared with group S, the mPAP and RVHI in the rats were
      significantly increased in group PE1, PE2, PE4, and PE6 (P<0.05); the indicators
      of vascular remodeling [(MA+PMA)%, RMT, and RMA] were markedly elevated in group
      PE4 and PE6 (P<0.05), but not in group PE1 and PE2. Immunohistochemical staining
      of TGF-beta1 and CTGF were more prominent in all of the right pneumonectomy
      groups than in the sham group. Western blot showed that the level of TGF-beta1
      protein was significantly increased in all of the right pneumonectomy groups
      (P<0.01), and the peak was observed in group PE2, whereas the level of CTGF
      protein was markedly elevated in group PE4 and PE6 (P<0.05), but no change was
      noticed in group PE1 and PE2. Compare to group S, the mRNA level of TGF-beta1 was
      dramatically increased in all right pneumonectomy groups (P<0.01), peaked at
      group PE2, and remained high in group PE4 and PE6. In contrast, the elevation of
      mRNA level of CTGF was not significant in group PE1, but group PE2, PE4 and PE6
      demonstrated significant mRNA level of CTGF (P<0.01). Correlation analysis showed
      that the protein and mRNA levels of CTGF were positively correlated with RMT and
      RMA ( r=0.743, r=0.906; P<0.05), while no correlation between the protein and
      mRNA level of TGF-beta1 with RMT or RMA. There was no correlation between the
      mRNA level of TGF-beta1 and CTGF. CONCLUSION: TGF-beta1 and CTGF play a role in
      the pathogenesis of increased pulmonary blood flow-induced pulmonary
      hypertension.

PMID- 23117455
TI  - [Respective analysis of dead patients with cirrhosis by Child-Pugh score and
      model of end-stage liver disease score].
AB  - OBJECTIVE: To understand the value of Child-Pugh (CP) classification and model of
      end-stage liver disease (MELD) score for patients with cirrhosis and their
      prognosis by retrospectively analyzing the two methods in hemorrhage death and
      non-hemorrhage death in patients with liver cirrhosis. METHODS: A total of 72
      patients who died of cirrhosis (the death group) were analyzed retrospectively,
      and the initial data in the hospital before death were collected. The initial
      information of the control group (88 patients) at the same time was also
      obtained. The death group was divided into two subgroups: esophagus varicosity
      burst massive hemorrhage death group and non-hemorrhage death group. RESULTS:
      MELD score and CP score of the death group (22.230+/-13.451, 10.264+/-2.028) were
      significantly higher than those of the control group (15.370+/-6.201, 9.318+/
      1.644; P<0.05). The MELD score and CP score for the massive bleeding death group
      were close to those of the control group. There was significant difference
      between the non-hemorrhage death group and the control group. The ratio of
      patients with CP grade A and MELD scores<20 died for massive bleeding in the
      death group was more than 70%, and that of CP grade C and MELD scores >= 30 in
      the death group was higher. ROC surve analysis found the accuracy of short-term
      predication of survival by MELD score and CP classification was improved after
      eliminating the risk factors of hemorrage. CONCLUSION: MELD and CP play a role in
      evaluating the state and prognosis of patients with cirrhosis. MELD score and CP
      classification predict the short-term survival efficiently on the premise of
      excluding the risk factors of esophagus and/or stomach bottom varicosity burst
      massive bleeding. CP and MELD scores are deficiencies, especially for low MELD
      score (<20) and CP level A patients. The prognostic accuracy may be improved when
      combining esophageal gastric fundal varices.

PMID- 23117456
TI  - [Expression of ADAMTS-2 and TGF-beta1 in cirrhotic liver].
AB  - OBJECTIVE: To explore the expression and distribution of a disintegrin and
      metalloprotease with thrombospondin motif (ADAMTS)-2 and transforming growth
      factor (TGF) -beta1 in patients with or without cirrhosis, and to determine their
      relation. METHODS: The liver tissues from 16 patients with cirrhotic portal
      hypertensive and 8 patients with liver injury were collected in Wuhan General
      Hospital from March to June, 2010. Immunohistochemistry and Western blot were
      applied to detect the protein expression of ADAMTS-2 and TGF-beta1. RESULTS:
      Immunohistochemistry showed that the expression of ADAMTS-2 and TGF-beta1 was
      significantly higher in the cirrhotic tissues than that in normal tissues
      (P<0.05). Western blot also showed the expression of ADAMTS-2 and TGF-beta1 in
      the cirrhosis tissues was significantly higher than that in normal tissues
      (P<0.05). There was a positive correlation between ADAMTS-2 and TGF-beta1
      (r=0.862, P<0.01). CONCLUSION: ADAMTS-2 and TGF-beta1 may have a synergistic
      reaction in promoting liver cirrhosis.

PMID- 23117457
TI  - [Factors and revision strategy for failure of thoracolumbar spine internal
      fixation after burst fracture].
AB  - OBJECTIVE: To analyze the reasons for the failure of thoracolumbar spine internal
      fixation after burst fracture, and to discuss the strategy for revision surgery.
      METHODS: From January 2005 to September 2010, 21 patients with thoracolumbar
      burst fracture received revision surgery after the failure of internal fixation.
      The etiology included loose of the fixation after anterior surgery in 4 patients,
      involving malunion with severe kyphosis in 1 patient, pedicle screw malposition
      in 3, fracture of adjacent segment vertebra in 2, broken of the fixation as non
      union of the fracture vertebra in 10 comprising obvious kyphotic deformity in 5,
      and 2 had developing kyphosis for over distraction of the vertebra followed by
      pseudarthrosis after removing the internal fixation. After the first operation,
      symptoms remained in 6 patients, deteriorated in 7, light to moderate improved in
      8. Surgical procedures such as anterior corpectomy and reconstruction,
      replacement of the internal fixation and canal decompression, vertebroplasty, and
      posterior pedicle subtraction osteotomy were directed based on individual
      situation. RESULTS: Patients were followed-up for 6-68 (27.0+/-13.2) months, and
      demonstrated solid fusion 6 to 12 months postoperatively. No failure of the
      internal fixation reccurred. No major complications or deterioration of
      neurologic status were noted. At the last follow-up, the improvement of Frankel
      grade was 0-2 (1.3+/-0.7). The mean visual analog scale (VAS) dropped down from
      7.6 to 2.1, and the mean oswestry disability index (ODI) decreased from 48.7 to
      10.3. Preoperative angle of 7 kyphotic deformity patients was 10 degree-75 degree
      (42.5 degree+/-15.3 degree), and was improved to -3 degree-10 degree (2.3
      degree+/-3.7 degree). At the last follow-up, the loss of correction was 0 degree
      1.3 degree (0.7 degree+/-0.3 degree), with the correction rate of 92.3%.
      CONCLUSION: Solid reconstruction of the anterior and middle column of the spine
      is the imperative procedure to prevent failure of internal fixation in
      thoracolumbar burst fractures. Revision surgery with reasonable strategy is
      beneficial and rewarding with few complications.

PMID- 23117458
TI  - [Delayed graft function after DCD kidney transplantation: risk factors for and
      impact on transplantation].
AB  - OBJECTIVE: To evaluate the risk factors of delayed graft function (DGF) and its
      impact on renal transplantation from donation after cardiac death (DCD). METHODS:
      We conducted a retrospective study consisting of 48 subjects who underwent a DCD
      kidney transplantation from February 2010 to March 2012. We classified the
      recipients into two groups: an IGF (immediate graft function) group (n=30) and a
      DGF group (n=18), and analyzed the risk factors of DGF and its impact on
      transplantation. RESULTS: DGF occurred in 18 of the 48 (37.5%) kidneys from DCD
      donors, and the occurrence of DGF did not adversely influence the survival of
      patients (P=0.098) and graft (P=0.447). In the univariate analysis, the
      preoperative dialysis time of recipients (P<0.001), HLA mismatch site (P<0.001),
      the cause of brain death (P=0.011), BMI (P<0.001), preoperative serum creatinine
      of donors (P=0.0001), norepinephrine used in donors (P<0.001), warm ischema time
      (WIT) (P<0.001), cold ischema time (CIT) (P<0.001) showed significant
      differences. In the multivariate analysis, cerebral hemorrhage as the cause of
      brain death (P=0.022, OR=39.652), preoperative serum creatinine of donors>=177
      MUmol/L (P=0.008, OR=57.148) and the preoperative dialysis time of recipients>=12
      months (P=0.060, OR=15.060) were independent risk factors for DGF development.
      CONCLUSION: The independent risk factors for DGF are the cause of brain death,
      the terminal creatinine level, and the preoperative dialysis time.

PMID- 23117459
TI  - [Risk factors for septic shock in patients with solid organ transplantation and
      complication of bacteremias].
AB  - OBJECTIVE: To explore the risk factors for septic shock in patients with solid
      organ transplantation and complication of bacteremias. METHODS: Clinical data of
      98 solid organ transplant cases with complication of bacteremias were
      retrospectively studied. All episodes of bacteremias met the CDC criteria. Six
      possible risk factors contributing to septic shock were evaluated by univariate
      analysis and multivariate logistic regression analysis. RESULTS: Among the 98
      patients, 133 times of bacteremias have been reported and 39 patients developed
      septic shock. Among the 39 patients with septic shock, 43.5%, 38.5%, 15.4% and
      2.6% of bacteremias were induced by multiple bacteria, gram-negative bacteria,
      gram-positive bacteria and fungi, respectively. The lung was the main source of
      bacteremias (41.8%), followed by intraabdominal/ biliary focus (24.5%). Risk
      factors for developing septic shock included the bacteremias happened in the 2nd
      to 8th week post transplant (P=0.014), polymicrobial etiology (P=0.001), intra
      abdominal/ biliary focus (P=0.011), and liver transplant (P=0.002). Only
      bacteremias occurred in the 2nd to 8th week post transplant and polymicrobial
      etiology were significant risk factors by multivariate analysis. CONCLUSION: Risk
      factors for developing septic shock in bacteremias after SOT are early-onset (the
      2nd-8th week post transplant) and polymicrobial etiology.

PMID- 23117460
TI  - [Association of MTHFR C677T and MS A2756G polymorphism with semen quality].
AB  - OBJECTIVE: To investigate the association of MTHFR C677T and MS A2756G
      polymorphism with semen quality in China. METHODS: The experimental group
      included 75 males with oligospermia, asthenospermia or teratospermia. The control
      group included 72 fertile males with normal fertility and sperm quality. The
      differences in the frequency of genetic polymorphism of MTHFR C677T and MS A2756G
      in the 2 groups were analyzed, and the plasma homocysteine (Hcy) level in both
      groups was detected. RESULTS: The frequency of MTHFR C677T genotypes (CT, TT and
      CT+TT) in the abnormal sperm group was higher than that in the control group
      (P<0.05), and it was the same case for T allele between the 2 groups (P<0.05).
      There was no difference in the frequency of MS A2756G genotypes between the two
      groups (P>0.05). The Hcy level in abnormal sperm group was higher than that in
      the control group. In all subjects, the Hcy level of the MTHFR genotypes (CT, TT
      and CT+TT) was higher than that of the CC genotype, with no difference among the
      three MS A2756G genotypes. CONCLUSION: CT and TT genotypes of MTHFR C677T are
      associated with abnormal sperm, which might be part of the pathogenesis of
      abnormal sperms. T allele may be the risk factor in China. The one mechanism of
      the association between MTHFR C677T polymorphism and semen quality could be
      higher Hcy level. MS A2756G polymorphism may not associate with semen quality in
      China.

PMID- 23117461
TI  - [Rapid detection of microalbuminuria with high-performance liquid
      chromatography].
AB  - OBJECTIVE: To develop a rapid detection method for microalbuminuria with size
      exclusion high performance liquid chromatography. METHODS: With a new mobile
      phase, samples were injected onto an Agilent Zorbax GF-250 size exclusion
      chromatographic column. The method was evaluated and urine albumin of 56 diabetic
      patients was analyzed. RESULTS: The mobile phase containing 0.1% formic acid and
      acetonitrile, with 20 MUL sample size, 1 mL/min flow rate, 205 nm detection
      wavelength. The retention time of albumin both in human serum and urine was 1.7
      min. The linear range was 5-2000 mg/L. The lower limit of measurement was 2 mg/L.
      The intra-assay coefficient of variation and the inter-assay coefficient of
      variation were 3.98% and 4.05% (20 mg/L), 3.55% and 3.60% (200 mg/L), 4.65% and
      4.74% (2000 mg/L), respectively. Recovery rates were 95.3%, 98.1%, and 97.2%.
      Microalbuminuria was detected in 30 samples by high performance liquid
      chromatography and 15 samples by immunoturbidimetry from 56 patients with
      diabetic mellitus. CONCLUSION: A fast and high sensitivity method, namely size
      exclusion high performance liquid chromatography, with mobile phase containing
      0.1% formic acid and acetonitrile has been established to analyze
      microalbuminuria, which can detect more microalbuminuria than other methods and
      is suitable for clinical routine measurement.

PMID- 23117462
TI  - [Novel dynamic TOPSIS method in evaluation for quality of medical care].
AB  - The quality of medical care shows characteristics of dynamic state with changes
      in time. However, many of appraisal and evaluation projects usually keep on the
      status of "past" or "present". Most of these models are static evaluation
      approach. In this study, besides the "past" and "present" status, we took one
      step further to unveil the future development trends of the medical therapeutical
      effects. Based on the index value and index increment, a dynamic TOPSIS method is
      presented. This method pays attention to both transverse and lengthwise
      information and can not only perform the evaluation on each time section but also
      can make the final dynamic evaluation. We applied this new method to the
      evaluation of quality of medical care, which was proved to be effective.

PMID- 23117463
TI  - [Large-capacity whole-lung lavage in 1 patient with pulmonary alveolar
      proteinosis and severe hypoxemia and literature review].
AB  - To improve the diagnosis and treatment of pulmonary alveolar proteinosis,
      clinical data for the first successfully treated case of pulmonary alveolar
      proteinosis with severe hypoxemia by large-capacity whole lung lavage in our
      hospital were analyzed, and relevant literatures were reviewed. A 35-year-old Han
      male initially presented two years ago with increasing cough and dyspnea was
      admitted to our hospital. Admission examination revealed severe hypoxemia,
      interstitial lung disease, and heavy protein deposition in the alveoli by lung
      biopsy. The patient received large-capacity whole-lung lavage in the operation
      room under general anesthesia and treatment of granulocyte-macrophage colony
      stimulating factor (GM-CSF). The patient's symptoms of dyspnea were alleviated
      markedly, and radiological findings improved and A-aDO2 decreased.

PMID- 23117464
TI  - [Effect of calcitonin gene-related peptide on the maturation of oocyte in vitro].
AB  - OBJECTIVE: To explore the effect of calcitonin gene-related peptide (CGRP) on
      murine oocyte maturation. METHODS: After injection of pregnant mare serum
      gonadotropin (PMSG, 10 U, i.p.) for 48 h, 6-week old female Kunming mice were
      killed, and the cumulus oocyte complexes (COCs) were collected from ovaries and
      inoculated in the culture plate by 30-40/hole. The COCs were treated with 4
      concentrations of CGRP (0, 10(-10), 10(-9), and 10(-8) mol/L), and the germinal
      vesicle breakdown (GVBD) and polar body I (PBI) were examined. Human granulosa
      cells were also cultured with CGRP (0, 10(-10), 10(-9), 10(-8) mol/L) and levels
      of intracellular cyclic adenosine monophosphate (cAMP) were measured. RESULTS:
      Exogenous CGRP caused a decrease in GVBD and PBI in COCs, and an increase in cAMP
      levels in human granulosa cells in a concentration-dependent manner. CONCLUSION:
      CGRP can inhibit the oocyte maturation, which may be related to the increased
      content of cAMP in granulosa cells.

PMID- 23117465
TI  - [Effect of CDK2-AP1 gene over-expression on proliferation and cell cycle
      regulation of breast cancer cell line MCF-7].
AB  - OBJECTIVE: To over-express cyclin-dependent kinase 2-associated protein 1 (CDK2
      AP1) gene, and investigate its effect on the proliferation and cell cycle
      regulation in breast cancer cell line MCF-7. METHODS: CDK2-AP1 gene coding region
      was cloned into lentivirus vector. Lentivirus particles were infected into MCF-7
      cells to upregulate the expression of CDK2-AP1 gene. The expression level of CDK2
      AP1 was detected at both mRNA and protein levels by real-time PCR and Western
      blot. MTT assay, colony formatting assay, and flow cytometry were performed to
      detect the change of proliferation and cell cycle in MCF-7 cells. We examined the
      expression of cell cycle associated genes (CDK2, CDK4, P16Ink4A, and
      P21Cip1/Waf1) followed by CDK2-AP1 over-expression by Western blot. RESULTS: CDK2
      AP1 gene was up-regulated significantly at both mRNA (6.94 folds) and protein
      level. MTT based growth curve, colony formatting assay and flow cytometry showed
      that CDK2-AP1 over-expression lentivirus inhibited the proliferation of MCF-7
      cells with statistical difference (P<0.05). In addition, with CDK2-AP1 over
      expression, MCF-7 cells were arrested in G1 phase accompanied by apoptosis.
      Western blot showed that the expression level of P21Cip1/Waf1 and P16 Ink4A was
      upregulated, while the expression level of CDK2 and CDK4, members of the CDK
      family, was downregulated. CONCLUSION: CDK2-AP1 gene plays a cancer suppressor
      role in breast cancer. Its function includes inhibiting the proliferation of MCF
      7 cells and arresting the cell cycle in G1 phase.

PMID- 23117466
TI  - [Effect of tetramethylpyrazine on the expression of macrophage migration
      inhibitory factor in acute spinal cord injury in rats].
AB  - OBJECTIVE: To determine the effect of tetramethylpyrazine (TMP) on the expression
      of migration inhibitory factor (MIF) in acute spinal cord injury (ASCI) in rats.
      METHODS: Allen's weight-drop method was used to establish a rat model of ASCI at
      T10. A total of 110 adult SD rats were divided into a sham operation group (group
      S, n=10), a control group (group C, n=50), and a TMP group (group T, n=50).
      Spinal cord functionality was measured by a modified Rivilin loxotic plate
      degree, BBB score, and combined behavioral score (CBS) at 1, 3, 5, 7, 14 and 21 d
      postoperatively. The injured spinal cord tissue samples were harvested at 1, 3,
      6, 12 h and 1, 3, 5, 7, 14, 21 d postoperatively (n=5 at each time point) and
      used to prepare continuous histological sections, in which the expression of MIF
      was analyzed by immunohistochemistry. RESULTS: The degree in group T measured by
      modified Rivlin loxotic plate test after the ASCI was significantly higher than
      that in group C at 7, 14, and 21 d (P<0.05). BBB score in group T was
      significantly higher than that in group C at 5, 7, 14, and 21 d after the ASCI
      (P<0.05). CBS score in group C was significantly higher than that in group T at
      5, 7, 14, and 21 d after the ASCI (P<0.05). The significantly low number of MIF
      positive cells was shown in group T when compared with that in group C at 12 h
      and 1, 3, 5, 7 d after the ASCI (P<0.05). As time passed, there was negative
      correlation between modified Rivlin loxotic plate degree and MIF expression and
      also between BBB score and MIF, and there was positive correlation between CBB
      score and MIF expression. CONCLUSION: TMP has protective effect after the ASCI,
      and may promote the repair of injured spinal cord tissues. TMP may decrease the
      MIF expression in cells after the ASCI.

PMID- 23117468
TI  - Trajectories of social engagement and depressive symptoms among long-term care
      facility residents in Hong Kong.
AB  - BACKGROUND: although social engagement and depressive symptoms are important
      concerns for long-term care facility residents, the dynamic relationship between
      them has not been adequately studied. OBJECTIVE: this study examines the
      relationship between social engagement and depressive symptoms and changes in
      social engagement and depressive symptoms among Chinese residents of long-term
      care facilities over 6 years. DESIGN AND METHODS: a latent growth model was used
      to analyse six waves of data collected using the Resident Assessment Instrument
      Minimum Data Set 2.0 in the Hong Kong Longitudinal Study on Long-Term Care
      Facility Residents. Ten residential facilities with a total of 1,184 eligible
      older adults at baseline were included in the study. RESULTS: after controlling
      for demographic variables at baseline, a higher level of social engagement was
      associated with fewer depressive symptoms. Trajectories of social engagement were
      significantly related to trajectories of depressive symptoms. Participants who
      recorded positive social engagement growth reported reduction in depressive
      symptoms. CONCLUSION: the findings of our study extend previous research by
      showing that increased social engagement is associated with decreased depressive
      symptoms over time. In long-term residential care settings, it is important for
      services to engage residents in meaningful social activities in order to reduce
      depressive symptoms.

PMID- 23117467
TI  - Objective measurements of daily physical activity patterns and sedentary
      behaviour in older adults: Age, Gene/Environment Susceptibility-Reykjavik Study.
AB  - BACKGROUND: objectively measured population physical activity (PA) data from
      older persons is lacking. The aim of this study was to describe free-living PA
      patterns and sedentary behaviours in Icelandic older men and women using
      accelerometer. METHODS: from April 2009 to June 2010, 579 AGESII-study
      participants aged 73-98 years wore an accelerometer (Actigraph GT3X) at the right
      hip for one complete week in the free-living settings. RESULTS: in all subjects,
      sedentary time was the largest component of the total wear time, 75%, followed by
      low-light PA, 21%. Moderate-vigorous PA (MVPA) was <1%. Men had slightly higher
      average total PA (counts * day(-1)) than women. The women spent more time in low
      light PA but less time in sedentary PA and MVPA compared with men (P < 0.001). In
      persons <75 years of age, 60% of men and 34% of women had at least one bout >=10
      min of MVPA, which decreased with age, with only 25% of men and 9% of women 85
      years and older reaching this. CONCLUSION: sedentary time is high in this
      Icelandic cohort, which has high life-expectancy and is living north of 60
      degrees  northern latitude.

PMID- 23117469
TI  - Safety and efficacy of a newly developed baby-sphincterotome for cannulation and
      precut in cases of failed selective wire-guided bile duct access:  a prospective
      8-year clinical evaluation.
AB  - BACKGROUND: Precut sphincterotomy (PCS) is a well-established alternative after
      repeated unsuccessful attempts of common bile duct (CBD) cannulation using
      standard catheters and/or guide-wire. Commonly used instruments for precutting
      are the needle-knife and a modified traction-type sphincterotome. In 1996, a so
      called 'baby-sphincterotome' with a preshaped, small-caliber 3 Fr tip was
      developed, which enables cannulation and precutting in one step. OBJECTIVE: A
      clinical evaluation was carried out and the complication rates were determined at
      a tertiary referral hospital. DESIGN: Prospective clinical evaluation.
      INTERVENTIONS: During an 8-year period, a total of 5389 endoscopic retrograde
      cholangiopancreatographies were performed at our hospital. In total, 1886
      patients fulfilled the inclusion criteria for this prospective study. The baby
      sphincterotome was used in 345 of 1886 patients (mean age 63.4 +/- 16.4 years,
      203 women) after five unsuccessful attempts of CBD cannulation using a
      hydrophilic guide-wire. After two more failed CBD cannulations with the baby
      sphincterotome, PCS was performed using the same device. MAIN OUTCOME
      MEASUREMENTS: The success rates of biliary access, postendoscopic retrograde
      cholangiopancreatography pancreatitis, and bleeding were assessed. RESULTS:
      Initially, the success rate of CBD cannulation on using the baby-sphincterotome
      was 28% (96/345 patients). Postinterventional pancreatitis occurred in two of 96
      patients (2%) and minor bleeding occurred during traction-type sphincterotomy in
      four of 93 patients (4%). In the remaining 249 patients precut with a baby
      sphincterotome, CBD cannulation was achieved in 219 cases (88%), although with
      pancreatitis and severe bleeding in 4% each. In 30 of 249 patients (12%), a
      second or a third (n=5) intervention was necessary, with a success rate of 73%
      (22/30 cases) after PCS. LIMITATIONS: This was a single-centre, uncontrolled
      study. CONCLUSION: The newly developed baby-sphincterotome enables bile duct
      access in a single session in 91% of the patients when guide-wire cannulation has
      failed. Direct cannulation was possible in about one-quarter of the patients,
      whereas PCS with the new device showed a high efficacy and a low complication
      rate.

PMID- 23117470
TI  - Treatment with a potassium-iron-phosphate-citrate complex improves PSE scores and
      quality of life in patients with minimal hepatic encephalopathy:  a multicenter,
      randomized, placebo-controlled, double-blind clinical trial.
AB  - OBJECTIVE: Minimal hepatic encephalopathy (MHE) is one of the possible
      complications of liver cirrhosis. In this study, a potassium-iron-phosphate
      citrate complex was analyzed for its efficacy and safety in the treatment of MHE,
      as this complex is supposed to bind to the major pathogenic factor of MHE:
      intestinal ammonia. MATERIALS AND METHODS: In this placebo-controlled, double
      blind clinical trial, 51 patients with MHE were randomized into two groups at a
      ratio of 1 : 1 and treated for 4 weeks either with a potassium-iron-phosphate
      citrate complex or a placebo. The efficacy of treatment was assessed according to
      changes in the portosystemic encephalopathy (PSE) score. Further assessments
      included alterations in quality of life and safety evaluations. RESULTS:
      Significantly more patients showed improvements in the PSE syndrome test from
      pathological to nonpathological PSE scores in the potassium-iron-phosphate
      citrate-treated group (72.0%) than in the placebo group (26.9%; P=0.0014).
      Furthermore, quality of life improved at a higher grade in the verum group (by
      0.7 +/- 0.6 U) compared with the placebo group (by 0.2 +/- 0.6 U; P=0.0036).
      Adverse events occurring in 28.0% of potassium-iron-phosphate-citrate-treated
      patients were generally mild or moderate and affected mainly the gastrointestinal
      tract. CONCLUSION: Treatment with potassium-iron-phosphate-citrate significantly
      improved PSE scores and quality of life in patients with MHE. The potassium-iron
      phosphate-citrate complex is a well-tolerated treatment option in MHE.

PMID- 23117471
TI  - Faecal microbiota transplantation for severe Clostridium difficile infection in
      the intensive care unit.
AB  - We describe a case of faecal microbiota transplantation (FMT) used for severe
      binary toxin-positive Clostridium difficile infection in an intensive care
      setting. The patient was admitted to the ICU of a tertiary hospital and failed
      traditional maximal pharmacological management. Adjunctive therapy with FMT given
      through gastroscopy resulted in resolution of the C. difficile-related symptoms.
      Although there is a growing experience with FMT for recurrent C. difficile
      infection, published evidence in severe disease is very limited. In a landscape
      of increasingly severe C. difficile infection, adjunctive FMT may be considered a
      useful early treatment option.

PMID- 23117472
TI  - Hair tourniquet syndrome.
AB  - A 6-year-old girl presented with necrosis of the left labium minus. An encircled
      hair at the base of the lesion was seen, and the diagnosis genital hair
      tourniquet syndrome was made. Genital hair tourniquet syndrome in children is a
      rare but potentially severe syndrome that requires immediate medical attention to
      prevent resulting necrosis.

PMID- 23117473
TI  - Complementary and alternative medicine in children.

PMID- 23117474
TI  - The impact of preoperative lymph node size on long-term outcome following
      curative gastrectomy for gastric cancer.
AB  - BACKGROUND: Multidetector-row computed tomography (MDCT) is widely used to
      predict pathological nodal status. However, an appropriate nodal size cutoff
      value to predict pathological nodal status has not been determined, and the
      impact of preoperative lymph node size on long-term outcomes is unclear. METHODS:
      This study included 137 gastric cancer patients with nodal involvement who
      underwent R0 gastrectomy between September 2002 and December 2006. Lymph nodes
      with a short-axis diameter of 10 mm or more as measured by MDCT were regarded as
      metastasized. An appropriate cutoff value with a high positive predictive value
      (PPV) and high specificity also was identified, and the subsequent
      clinicopathological characteristics and long-term outcomes were investigated.
      RESULTS: A cutoff value of 15 mm was found to be appropriate for grouping
      patients into large (>=15 mm) and small (<15 mm) lymph node metastasis (LLNM and
      SLNM) groups, with a high PPV (98.6 %) and specificity (99.8 %). There were no
      differences in clinicopathological characteristics between the groups except for
      pathological nodal status. In the LLNM group, the 5-year survival rate was 55 %,
      which was significantly lower than in the SLNM group (73.2 %; P = 0.008). After
      stratification by tumor depth, the same trend was observed in patients with pT3
      disease (46.8 % vs. 72.7 %; P = 0.015) and those with pT4 disease (14.3 % vs.
      64.8 %; P = 0.035). CONCLUSIONS: Gastric cancer patients with lymph nodes
      measuring 15 mm or more preoperatively have worse long-term outcomes. These
      patients would therefore be suitable candidates for future clinical trials
      investigating the efficacy of neoadjuvant chemotherapies.

PMID- 23117475
TI  - Physiology, not chronology, dictates outcomes after esophagectomy for esophageal
      cancer: outcomes in patients 80 years and older.
AB  - PURPOSE: To assess short and long-term outcomes for patients aged >=80 years
      undergoing esophagectomy for malignancy. METHODS: All patients undergoing
      esophagectomy for cancer between 1991 and 2011 had information prospectively
      entered into a database; patients were divided into elderly (>=80 years) and
      younger (<80 years) groups. RESULTS: Of the 500 patients included, 32 (6.4%) were
      >=80 years of age. Octogenarians had increased Charlson comorbidity index and
      were less likely to receive neoadjuvant chemoradiotherapy (6.3 vs. 39.7%).
      Analysis of operative time, estimated blood loss, and length of intensive care
      unit and hospital stay revealed no significant differences between the groups.
      Patients >=80 years old had increased total postoperative morbidity (68.8 vs.
      44.9%), specifically arrhythmia (31.3 vs. 16.7%) and pneumonia (18.8 vs. 8.3%).
      There were no in-hospital mortalities in patients >=80 years (0 vs. 0.4%), and
      there was no significant difference in overall survival between the groups (53.2
      +/- 9.1 vs. 77.6 +/- 4.8 months; P = 0.58). Subset analysis demonstrated similar
      morbidity and length of hospital stay for patients between 70 and 79 years (n =
      132) and those >=80 years. CONCLUSIONS: Elderly patients undergoing esophagectomy
      are at greater risk of postoperative complications. However, there were no
      significant differences in other major parameters, including length of hospital
      stay, mortality, and survival, indicating that selected patients >=80 years old
      can and should be assessed by an experienced surgeon.

PMID- 23117476
TI  - Frequent alterations of MCPH1 and ATM are associated with primary breast
      carcinoma: clinical and prognostic implications.
AB  - BACKGROUND: MCPH1 is a proximal regulator of DNA damage response pathway that is
      involved in recruitment of phosphorylated ATM to double-stranded DNA breaks.
      METHODS: To understand the importance of MCPH1 and ATM in deregulation of DNA
      damage response pathway in breast carcinoma, we studied m-RNA expression and
      genetic/epigenetic alterations of these genes in primary breast carcinoma
      samples. RESULTS: Our study revealed reduced expression (mRNA/protein) and high
      alterations (deletion/methylation) (96 %, 121 of 126) of MCPH1 and ATM. Mutation
      was, however, rare in inactivation of MCPH1. In immunohistochemical analysis,
      reduced protein expression of MCPH1, ATM and p-ATM were concordant with their
      molecular alterations (P = 0.03-0.01). Alterations of MCPH1 and deletion of ATM
      were significantly high in estrogen/progesterone receptor-negative than
      estrogen/progesterone receptor-positive breast carcinoma samples compared to
      early or late age of onset tumors, indicating differences in pathogenesis of the
      molecular subtypes (P = 0.004-0.01). These genes also showed differential
      association with tumor stage, grade and lymph node status in different subtypes
      of breast carcinoma (P = 0.00001-0.01). Their coalterations showed significant
      association with tumor progression and prognosis (P = 0.003-0.05). Interestingly,
      patients with alterations of these genes or MCPH1 alone had poor outcome after
      treatment with DNA-interacting drugs and/or radiation (P = 0.01-0.05).
      CONCLUSIONS: Inactivation of MCPH1-ATM-associated DNA damage response pathway
      might have an important role in the development of breast carcinoma with
      diagnostic, prognostic and therapeutic implications.

PMID- 23117477
TI  - Correlation between three assay systems for anti-Mullerian hormone (AMH)
      determination.
AB  - PURPOSE: Analysis of anti-Mullerian hormone (AMH) is becoming of recognized
      importance in reproductive medicine, but assays are not standardized. We have
      evaluated the correlation between the new Gen II ELISA kit (Beckman-Coutler) and
      the older ELISA kits by Immunotech (IOT) and Diagnostic Systems Laboratories
      (DSL). METHODS: A total of 56 archived serum samples from patients with
      subfertility or reproductive endocrine disorders were retrieved and assayed in
      duplicate using the three AMH ELISA kits . The samples covered a wide range of
      AMH concentrations (1.9 to 142.5 pmol/L). RESULTS: We observed good correlations
      between the new (AMH Gen II) and old AMH assay kits by IOT and DSL (R(2) = 0.971
      and 0.930 respectively). The regression equations were AMH (Gen II) = 1.353 * AMH
      (IOT) + 0.051 and AMH (Gen II) = 1.223 * AMH (DSL) - 1.270 respectively.
      CONCLUSIONS: AMH concentrations using the Gen II kit are slightly higher than
      those from the IOT and DSL kits. Standardization of assay results worldwide is
      urgently required but this analysis facilitates the interpretation of values
      obtained historically and in future studies using any of the 3 assays available.
      Meanwhile, adapting clinical cut-offs from previously published work by direct
      conversion is not recommended.

PMID- 23117478
TI  - Bevacizumab-containing chemotherapy for non-small cell lung cancer patients: a
      population-based observational study by the Ibaraki thoracic integrative
      (POSITIVE) research group.
AB  - To evaluate the efficacy and safety of bevacizumab-containing chemotherapy for
      non-small cell lung cancer (NSCLC), we performed a population-based observational
      study. The efficacy and safety of bevacizumab-containing chemotherapy for NSCLC
      patients were evaluated at 14 sites (17 hospital departments) in a prefecture of
      Japan between December 2009 and August 2011. Complete data sets were obtained
      from 159 patients with NSCLC. The median age was 66 years, and 34.0 % of the
      patients were 70 years or older. The overall response rate to bevacizumab therapy
      was 41.6 %, and the disease control rate was 78.5 %. In 88 patients who received
      bevacizumab-containing chemotherapy as first-line therapy, the response and
      disease control rates were 55.0 and 78.9 %, respectively. The incidence of
      clinically significant (grade 3 or more) adverse events was generally low:
      proteinuria occurred in 2 (1.3 %) patients, hypertension in 2 (1.3 %), hemoptysis
      in 1 (0.6 %), and interstitial pneumonia in 1 (0.6 %). The time to treatment
      failure (TTF) in the 159 patients was 169 days, and the median overall survival
      (OS) was 580 days. In patients who received bevacizumab-containing chemotherapy
      as first-line therapy, the TTF and OS were 152 and 520 days, respectively. The
      difference in TTF between patients who received bevacizumab-containing
      chemotherapy as first-line therapy and those who received it as second-line or
      later-line therapy was not significant (p = 0.4971). With regard to first-line
      therapy, the difference in TTF between patients treated with carboplatin +
      pemetrexed + bevacizumab and those treated with carboplatin + paclitaxel +
      bevacizumab was not significant (p = 0.9435). We deduced that bevacizumab
      containing chemotherapy is effective against NSCLC and also tolerable in clinical
      practice.

PMID- 23117479
TI  - A novel carboxymethylcellulose-gelatin-titanium dioxide-superoxide dismutase
      biosensor; electrochemical properties of carboxymethylcellulose-gelatin-titanium
      dioxide-superoxide dismutase.
AB  - A novel highly sensitive electrochemical carboxymethylcellulose-gelatin-TiO(2)
      superoxide dismutase biosensor for the determination of O(2)(*-) was developed.
      The biosensor exhibits high analytical performance with a wide linear range (1.5
      nM to 2 mM), low detection limit (1.5 nM), high sensitivity and low response time
      (1.8s). The electron transfer of superoxide dismutase was first accomplished at
      the carboxymethylcellulose-gelatin-Pt and carboxymethylcellulose-gelatin-TiO(2)
      Pt surface. The electron transfer between superoxide dismutase and the
      carboxymethylcellulose-gelatin-Pt wihout Fe(CN)(6)(4-/3-) and
      carboxymethylcellulose-gelatin-Pt, carboxymethylcellulose-gelatin-TiO(2)-Pt with
      Fe(CN)(6)(4-/3-) is quasireversible with a formal potential of 200 mV, 207 mV,
      and 200 mV vs Ag|AgCl respectively. The anodic (ks(a)) and cathodic (ks(c))
      electron transfer rate constants and the anodic (alpha(a)) and cathodic
      (alpha(c)) transfer coefficients were evaluated: ks(a)=6.15 s(-1), alpha(a)=0.79,
      and ks(c)=1.48 s(-1) alpha(c)=0.19 for carboxymethylcellulose-superoxide
      dismutase without Fe(CN)(6)(4-/3-), ks(a)=6.77 s(-1), alpha(a)=0.87, and ks(c)=1
      s(-1) alpha(c)=0.13 for carboxymethylcellulose-superoxide dismutase with
      Fe(CN)(6)(4-/3-), ks(a)=6.85 s(-1), alpha(a)=0.88, and ks(c)=0.76 s(-1)
      alpha(c)=0.1 carboxymethylcellulose-gelatin-TiO(2)-superoxide dismutase. The
      electron transfer rate between superoxide dismutase and the Pt electrode is
      remarkably enhanced due to immobilizing superoxide dismutase in
      carboxymethylcellulose-gelatin and TiO(2) nanoparticles tend to act like
      nanoscale electrodes.

PMID- 23117480
TI  - Correlation of rutin accumulation with 3-O-glucosyl transferase and phenylalanine
      ammonia-lyase activities during the ripening of tomato fruit.
AB  - In tomato, the predominant flavonoid is quercetin-3-rutinoside (rutin). In this
      study, we aim to investigate the phenylalanine ammonia-lyase (PAL) and the
      quercetin-3-O-glucosyl transferase (3-GT) reactions in the formation of rutin
      during tomato fruit ripening. Tomatoes of the Moneymaker variety at different
      development stages (green, breaker, turning, pink, red, and deep red) were
      divided into flesh and peel fractions. In each sample, both the content of rutin
      and the enzymatic activities for PAL and 3-GT were recorded. The highest
      activities of PAL were recorded in the peel of turning fruit (3,000 MUkat/mg
      fresh weight). In fruit flesh, maximal activity was observed in red fruit (917.3
      MUkat/mg). For both tissues, PAL activity strongly decreased at the final (deep
      red) fruit stage. The activity of 3-GT in peel peaked in the turning fruit stage
      (50.7 pkat/mg), while in flesh maximal activity (33.4 pkat/mg) was observed in
      green fruit, which rapidly declined at the turning stage. Higher levels of rutin
      were detected in the tomato peel compared to the flesh part with the highest
      level being found at the green stage. The relation of PAL and 3-GT activities to
      rutin content is also evaluated.

PMID- 23117481
TI  - Effects of sample delivery on analyte capture in porous bead sensors.
AB  - Sample delivery is a crucial aspect of point-of-care applications where sample
      volumes need to be low and assay times short, while providing high analytical and
      clinical sensitivity. In this paper, we explore the influence of the factors
      surrounding sample delivery on analyte capture in an immunoassay-based sensor
      array manifold of porous beads resting in individual wells. We model using
      computational fluid dynamics and a flow-through device containing beads
      sensitized specifically to C-reactive protein (CRP) to explore the effects of
      volume of sample, rate of sample delivery, and use of recirculation vs.
      unilateral delivery on the effectiveness of the capture of CRP on and within the
      porous bead sensor. Rate of sample delivery lends to the development of a time
      dependent, shrinking depletion region around the bead exterior. Our findings
      reveal that at significantly high rates of delivery, unique to porous bead
      substrates, capture at the rim of the bead is reaction-limited, while capture in
      the interior of the bead is transport-limited. While the fluorescence signal
      results from the aggregate of captured material throughout the bead, multiple
      kinetic regimes exist within the bead. Further, under constant pressure
      conditions dictated by the array architecture, we reveal the existence of an
      optimal flow rate that generates the highest signal, under point-of-care
      constraints of limited-volume and limited-time. When high sensitivity is needed,
      recirculation can be implemented to overcome the analyte capture limitations due
      to volume and time constraints. Computational simulations agree with experimental
      results performed under similar conditions.

PMID- 23117482
TI  - Genetic study of axon regeneration with cultured adult dorsal root ganglion
      neurons.
AB  - It is well known that mature neurons in the central nervous system (CNS) cannot
      regenerate their axons after injuries due to diminished intrinsic ability to
      support axon growth and a hostile environment in the mature CNS(1,2). In
      contrast, mature neurons in the peripheral nervous system (PNS) regenerate
      readily after injuries(3). Adult dorsal root ganglion (DRG) neurons are well
      known to regenerate robustly after peripheral nerve injuries. Each DRG neuron
      grows one axon from the cell soma, which branches into two axonal branches: a
      peripheral branch innervating peripheral targets and a central branch extending
      into the spinal cord. Injury of the DRG peripheral axons results in substantial
      axon regeneration, whereas central axons in the spinal cord regenerate poorly
      after the injury. However, if the peripheral axonal injury occurs prior to the
      spinal cord injury (a process called the conditioning lesion), regeneration of
      central axons is greatly improved(4). Moreover, the central axons of DRG neurons
      share the same hostile environment as descending corticospinal axons in the
      spinal cord. Together, it is hypothesized that the molecular mechanisms
      controlling axon regeneration of adult DRG neurons can be harnessed to enhance
      CNS axon regeneration. As a result, adult DRG neurons are now widely used as a
      model system to study regenerative axon growth(5-7). Here we describe a method of
      adult DRG neuron culture that can be used for genetic study of axon regeneration
      in vitro. In this model adult DRG neurons are genetically manipulated via
      electroporation-mediated gene transfection(6,8). By transfecting neurons with DNA
      plasmid or si/shRNA, this approach enables both gain- and loss-of-function
      experiments to investigate the role of any gene-of-interest in axon growth from
      adult DRG neurons. When neurons are transfected with si/shRNA, the targeted
      endogenous protein is usually depleted after 3-4 days in culture, during which
      time robust axon growth has already occurred, making the loss-of-function studies
      less effective. To solve this problem, the method described here includes a re
      suspension and re-plating step after transfection, which allows axons to re-grow
      from neurons in the absence of the targeted protein. Finally, we provide an
      example of using this in vitro model to study the role of an axon regeneration
      associated gene, c-Jun, in mediating axon growth from adult DRG neurons(9).

PMID- 23117483
TI  - Facile synthesis of spiro[indoline-3,3'-pyrrolo[1,2-a]quinolines] and
      spiro[indoline-3,1'-pyrrolo[2,1-a]isoquinolines] via 1,3-dipolar cycloaddition
      reactions of heteroaromatic ammonium salts with 3-phenacylideneoxindoles.
AB  - A series of complex spiro[indoline-3,3'-pyrrolo[1,2-a]quinolines] were
      efficiently synthesized by 1,3-dipolar cycloaddition reactions of N
      phenacylquinolinium bromides with 3-phenacylideneoxindoles in ethanol with
      triethylamine as base. Under similar conditions the 1,3-cycloadditions of N
      phenacylisoquinolinium and N-phenacyl-1,10-phenanthrolinium bromides with 3
      phenacylideneoxindoles resulted in the corresponding spiro[indoline-3,1'
      pyrrolo[2,1-a]isoquinoline] and spiro[benzo[h]pyrrolo[1,2-a]quinoline-3,3'
      indoline] derivatives in good yields. The characterization data of spiro
      compounds and single crystal determination indicated that this 1,3-cycloaddition
      reaction is a regioselective and diastereoselective reaction and all prepared
      spiro compounds exist in the thermodynamically stable trans isomer.

PMID- 23117484
TI  - In vivo electromechanical reshaping of ear cartilage in a rabbit model: a
      minimally invasive approach for otoplasty.
AB  - OBJECTIVE: To report the first successful study to date of in vivo
      electromechanical reshaping of ear cartilage in a rabbit model. METHODS: Ears of
      New Zealand white rabbits were reshaped using percutaneous needle electrode
      electromechanical reshaping (5 V for 4 minutes) and were then bolstered for 4
      weeks. Ten ears were treated, with 2 undergoing sham procedures and serving as
      controls. The treatment was performed using a platinum array of electrodes
      consisting of 4 parallel rows of needles inserted across the region of flexures
      in the ear. After 4 weeks, the animals were killed, and the ears were
      photographed and sectioned for conventional light microscopy and confocal
      microscopy (live-dead fluorescent assays). RESULTS: Significant shape change was
      noted in all the treated ears (mean, 102.4 degrees ; range, 87 degrees -122
      degrees ). Control ears showed minimal shape retention (mean, 14.5 degrees ;
      range, 4 degrees -25 degrees ). Epidermis and adnexal structures were preserved
      in reshaped ears, and neochondrogenesis was noted in all the specimens. Confocal
      microscopy demonstrated a localized zone of nonviable chondrocytes (<2.0 mm in
      diameter) surrounding needle sites in all the treated ears. CONCLUSIONS:
      Electromechanical reshaping can alter the shape of the rabbit auricle, providing
      good creation and retention of shape, with limited skin and cartilage injury.
      Needle electrode electromechanical reshaping is a viable technique for minimally
      invasive tissue reshaping, with potential applications in otoplasty, septoplasty,
      and rhinoplasty. Further studies to refine dosimetry parameters will be required
      before clinical trials.

PMID- 23117485
TI  - miR-27a regulates the self renewal of the H446 small cell lung cancer cell line
      in vitro.
AB  - Cancer growth is driven by cancer stem-like cells within a tumor, called cancer
      stem cells (CSCs). Since miRNAs can regulate cell-fate decisions, we compared
      miRNA expression in stem-like cells and differentiated cells from small cell lung
      cancer (SCLC) cell lines to develop further understanding of the molecular
      mechanisms involved in the pathogenesis of SCLC. First, SCLC stem-like cells were
      enriched by isolating sphere-forming cells using a defined serum-free medium.
      Further, microRNA microarrays were used to measure the expression of 1212 miRNAs
      in sphere-forming cells and parental cells. We found 86 miRNAs that were
      differentially expressed, including 48 upregulated miRNAs and 38 downregulated
      miRNAs between sphere-forming cells and parental cells. Among them, five
      downregulated miRNAs (let-7, miR-20, 21, 27a and 30b) and one upregulated miRNA
      (miR-149*) were selected for validation in 3 sets of SCLC cell lines by qRT-RCR.
      The qRT-PCR analysis confirmed that all six miRNAs were indeed differentially
      expressed. However, only miR-27a was consistently downregulated in sphere-forming
      cells of all 3 cell lines. Antagonizing miR-27a by inhibitor in parental cells
      enhanced proliferation, self renewal, and the proportion of undifferentiated
      cells in vitro. The candidate miRNA and some miRNAs with same seed sequence are
      predicted to have several target genes related to apoptosis, cell proliferation
      and cell cycle. Our results suggest that downregulation of miR-27a enhanced the
      stem-like properties of SCLC cells in vitro and may be critical to maintaining a
      stem cell function in SCLC.

PMID- 23117486
TI  - Constructing "behavioral" comparison groups: A difference-in-difference analysis
      of the effect of copayment based on the patient's price elasticity.
AB  - It is well known that the differences-in-differences (DD) estimator is based on
      the assumption that in the absence of treatment, the average outcomes for the
      treated group and the control group will follow a common trend over time. That
      can be problematic, especially when the selection for the treatment is influenced
      by the individual's unobserved behavior correlating with the medical utilization.
      The aim of this study was to develop an index for controlling a patient's
      unobserved heterogeneous response to reform, in order to improve the
      comparability of treatment assignment. This study showed that a DD estimator of
      the reform effects can be decomposed into effects induced by moral hazard and by
      changes in health risk within the same treated/untreated group. This article also
      presented evidence that the constructed index of the price elasticity of the
      adjusted clinical group has good statistical properties for identifying the
      impact of reform.

PMID- 23117487
TI  - Isolated theory of mind deficits and risk for frontotemporal dementia: a
      longitudinal pilot study.
AB  - OBJECTIVE: Recent data suggest that theory of mind (ToM) deficits represent an
      early symptom of the behavioural variant of frontotemporal dementia (bvFTD).
      However, longitudinal data on the natural history of subjects presenting with
      isolated ToM deficits are lacking. The aim of the study was to verify if isolated
      ToM deficits represent an at-risk state for prefrontal dysfunction and bvFTD.
      METHODS: A population of healthy subjects (n=4150, age range: 50-60 years)
      completed a clinical and neuropsychological evaluation including the Reading the
      Mind in the Eyes Test (RMET), a widely used ToM task. From this group, we
      recruited a low-RMET group (n=83) including subjects with RMET scores lower than
      2 SDs but an otherwise normal neuropsychological evaluation and a control group.
      All subjects underwent evaluation at baseline and after 2 years. RESULTS:
      Subjects in the low-RMET group showed decline in prefrontal functions at follow
      up. Moreover, at follow-up 12 subjects in the low-RMET group presented with
      findings suggestive of bvFTD. Neuropsychological performance was stable in the
      control group. CONCLUSIONS: Our data suggest that isolated ToM deficits could
      represent an at-risk situation for the development of future prefrontal
      dysfunction and bvFTD. ToM evaluation should be included in neuropsychological
      protocols aimed to evaluate the early phases of dementia.

PMID- 23117488
TI  - Effect of the neutral CLOTS 1 trial on the use of graduated compression stockings
      in the Efficacy of Nitric Oxide Stroke (ENOS) trial.
AB  - BACKGROUND AND PURPOSE: Current evidence suggests that the time lag from the
      publication of randomised clinical trial results to changes in prescribing
      behaviour for drugs is gradually reducing. However, the effect of results of
      clinical trials of devices and non-pharmacological interventions on clinical
      practice is less clear. METHODS: Prospective data from the ongoing international
      'Efficacy of Nitric Oxide Stroke' (ENOS) trial were analysed to assess the use of
      graduated compression stockings (GCS) for deep vein thrombus (DVT) prophylaxis in
      acute stroke patients before and after publication of the large 'Clots in Legs Or
      sTockings after Stroke' (CLOTS-1) trial. RESULTS: Data on GCS use were available
      for 1971 patients with acute stroke enrolled into ENOS from February 2003 to
      April 2011; of these, 498 (25.3%) wore GCS. Prior to publication of CLOTS-1, GCS
      use was common (>50%) in the UK, Australasia and Canada but infrequent in Asia
      and the rest of Europe. After publication of CLOTS-1, use of GCS in the UK
      declined from 398/656 (61%) to 20/567 (4%) (p<0.001) but not elsewhere (eg, in
      Australasia (57% before publication vs 70% after publication, p=0.24, but based
      on small numbers). Practice change was apparent within 3 months of the study
      publication and was sustained thereafter. There was no change in DVT rates before
      and after CLOTS-1 (0.8% vs 1.0%). CONCLUSIONS: GCS use declined dramatically
      following the reporting of the CLOTS-1 trial. The results support the notion that
      a neutral trial of a device can influence clinical practice rapidly, which is
      important with a widely used and moderately expensive (time and finance)
      intervention.

PMID- 23117489
TI  - Phosphorylated neurofilament heavy subunit (pNF-H) in peripheral blood and CSF as
      a potential prognostic biomarker in amyotrophic lateral sclerosis.
AB  - BACKGROUND: The phosphorylated neurofilament heavy subunit (pNF-H), a major
      structural component of motor axons, is a promising putative biomarker in
      amyotrophic lateral sclerosis (ALS) but has been studied mainly in CSF. We
      examined pNF-H concentrations in plasma, serum and CSF as a potential biomarker
      for disease progression and survival in ALS. METHODOLOGY: We measured pNF-H
      concentration by monoclonal sandwich ELISA in plasma (n=43), serum and CSF (n=20)
      in ALS patients collected at the Mayo Clinic Florida and Emory University. We
      included plasma from an ALS cohort (n=20) from an earlier pilot study in order to
      evaluate baseline pNF-H levels in relation to disease progression using the
      Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), survival and
      anatomical region of ALS onset. RESULTS: Higher pNF-H levels in plasma, serum and
      CSF showed evidence of association with faster decline in ALSFRS-R. There was
      evidence for a relationship of higher serum and plasma pNF-H levels with shorter
      survival, although evidence was weaker for CSF. pNF-H concentration in plasma
      (n=62) may be higher in patients with bulbar onset than in patients with spinal
      onset. CONCLUSIONS: In ALS, increased pNF-H concentration in plasma, serum and
      CSF appears to be associated with faster disease progression. Factors affecting
      pNF-H levels or their detection in serum and plasma in relation to disease course
      may differ from those in CSF. Data raising the possibility that site of ALS onset
      (bulbar vs spinal) may influence pNF-H levels in peripheral blood seems
      noteworthy but requires confirmation. These data support further study of pNF-H
      in CSF, serum and plasma as a potential ALS biomarker.

PMID- 23117490
TI  - Progressive changes in a recognition memory network in Parkinson's disease.
AB  - BACKGROUND: In a previous functional MRI (fMRI) study, we found that patients
      with Parkinson's disease (PD) presented with dysfunctions in the recruitment of
      recognition memory networks. We aimed to investigate the changes in these
      networks over time. METHODS: We studied 17 PD patients and 13 age and sex matched
      healthy subjects. In both groups fMRI (recognition memory paradigm) and
      neuropsychological assessments were obtained at baseline and at follow-up. To
      analyse changes over time in functional networks, model free (independent
      component analysis) analyses of the fMRI data were carried out. Then, a cross
      correlation approach was used to assess the changes in the strength of functional
      connectivity. RESULTS: At follow-up, patients showed reduced recruitment of one
      network, including decreased activation in the orbitofrontal cortices, middle
      frontal gyri, frontal poles, anterior paracingulate cortex, superior parietal
      lobes and left middle temporal gyrus, as well as decreased deactivation in the
      anterior paracingulate gyrus and precuneus. Cross correlation analyses over time
      showed a decrease in the strength of functional connectivity between the middle
      frontal gyrus and the superior parietal lobe in PD patients. CONCLUSIONS: Model
      free fMRI and cross correlation connectivity analyses were able to detect
      progressive changes in functional networks involved in recognition memory in PD
      patients at early disease stages and without overt clinical deterioration.
      Functional connectivity analyses could be useful to monitor changes in brain
      networks underlying neuropsychological deficits in PD.

PMID- 23117492
TI  - Risk of epilepsy after traumatic brain injury: a retrospective population-based
      cohort study.
AB  - OBJECTIVE: To investigate the associated risk of epilepsy after traumatic brain
      injury (TBI) in a population-based retrospective cohort study. METHODS: Using
      Taiwan's National Health Insurance Research Database of reimbursement claims, we
      conducted a retrospective cohort study of 19 336 TBI patients and 540 322 non-TBI
      participants aged >=15 years as reference group. Data on newly developed epilepsy
      after TBI with 5-8 years' follow-up during 2000 to 2008 were collected. HRs and
      95% CIs for the risk of epilepsy associated with TBI were analysed with
      multivariate Cox proportional hazards regressions. RESULTS: Compared with the non
      TBI cohort, the adjusted HRs of developing epilepsy among TBI patients with skull
      fracture, severe or mild brain injury were 10.6 (95% CI 7.14 to 15.8), 5.05 (95%
      CI 4.40 to 5.79) and 3.02 (95% CI 2.42 to 3.77), respectively. During follow-up,
      men exhibited higher risks of post-TBI epilepsy. Patients who had mixed types of
      cerebral haemorrhage were at the highest risk of epilepsy compared with the non
      TBI cohort (HR 7.83, 95% CI 4.69 to 13.0). The risk of post-TBI epilepsy was
      highest within the first year after TBI (HR 38.2, 95% CI 21.7 to 67.0).
      CONCLUSIONS: The risk of epilepsy after TBI varied by patient gender, age, latent
      interval and complexity of TBI. Integrated care for early identification and
      treatment of post-trauma epilepsy were crucial for TBI patients.

PMID- 23117493
TI  - Executive dysfunction in ALS is not the whole story.

PMID- 23117491
TI  - Cognitive decline and reduced survival in C9orf72 expansion frontotemporal
      degeneration and amyotrophic lateral sclerosis.
AB  - BACKGROUND: Significant heterogeneity in clinical features of frontotemporal
      lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) cases with the
      pathogenic C9orf72 expansion (C9P) have been described. To clarify this issue, we
      compared a large C9P cohort with carefully matched non-expansion (C9N) cases with
      a known or highly-suspected underlying TAR DNA-binding protein 43 (TDP-43)
      proteinopathy. METHODS: A retrospective case-control study was carried out using
      available cross-sectional and longitudinal clinical and neuropsychological data,
      MRI voxel-based morphometry (VBM) and neuropathological assessment from 64 C9P
      cases (ALS=31, FTLD=33) and 79 C9N cases (ALS=36, FTLD=43). RESULTS: C9P cases
      had an earlier age of onset (p=0.047) and, in the subset of patients who were
      deceased, an earlier age of death (p=0.014) than C9N. C9P had more rapid
      progression than C9N: C9P ALS cases had a shortened survival (2.6 +/- 0.3 years)
      compared to C9N ALS (3.8 +/- 0.4 years; log-rank lambda2=4.183, p=0.041), and C9P
      FTLD showed a significantly greater annualised rate of decline in letter fluency
      (4.5 +/- 1.3 words/year) than C9N FTLD (1.4 +/- 0.8 words/year, p=0.023). VBM
      revealed greater atrophy in the right frontoinsular, thalamus, cerebellum and
      bilateral parietal regions for C9P FTLD relative to C9N FTLD, and regression
      analysis related verbal fluency scores to atrophy in frontal and parietal
      regions. Neuropathological analysis found greater neuronal loss in the mid
      frontal cortex in C9P FTLD, and mid-frontal cortex TDP-43 inclusion severity
      correlated with poor letter fluency performance. CONCLUSIONS: C9P cases may have
      a shorter survival in ALS and more rapid rate of cognitive decline related to
      frontal and parietal disease in FTLD. C9orf72 genotyping may provide useful
      prognostic and diagnostic clinical information for patients with ALS and FTLD.

PMID- 23117494
TI  - Long-term prognosis of aphasia after stroke.
AB  - BACKGROUND: The long-term functional outcome of aphasia after stroke is
      uncertain, even though this information is needed as early as possible for
      adequate patient care and support. This observational prospective study was aimed
      at predicting functional outcome at 1 year after stroke. METHODS: We examined
      linguistic components (ScreeLing) and functional verbal communication (Aphasia
      Severity Rating Scale, ASRS) in 147 aphasic patients. The ScreeLing was
      administered at 1, 2 and 6 weeks after stroke; the ASRS at 1 week and 1 year. The
      relationships between linguistic, demographic and stroke characteristics, and
      good functional outcome at 1 year (ASRS 4 or 5) were examined with logistic
      regression analyses. RESULTS: The baseline linguistic components (ie, semantics,
      phonology and syntax) were significant predictors (p<0.001) for 1-year outcome in
      univariable analyses. In multivariable analysis, these variables explained 46.5%
      of the variance, with phonology being the only significant predictor (p=0.003).
      Age, Barthel Index score, educational level and haemorrhagic stroke were
      identified as other significant predictors of outcome. A prognostic model of
      these five baseline predictors explained 55.7% of the variance. The internally
      validated area under the receiver operating characteristic curve (AUC) was 0.89,
      indicating good predictive performance. Adding the degree of phonological
      recovery between 1 and 6 weeks after stroke to this model increased the explained
      variance to 65% and the AUC to 0.91. CONCLUSIONS: The outcome of aphasia at 1
      year after stroke can be predicted in the first week by the phonology score, the
      Barthel Index score, age, educational level and stroke subtype, with phonology
      being the strongest predictor.

PMID- 23117495
TI  - Prognosis of acute subdural haematoma from intracranial aneurysm rupture.
AB  - BACKGROUND: Acute subdural haematoma (aSDH) is a rare complication of aneurysmal
      subarachnoid haemorrhage (SAH) and is associated with poor clinical condition on
      admission and poor outcome. OBJECTIVE: The aim of this study was to assess
      whether aneurysmal aSDH is an independent risk factor for poor outcome. METHODS:
      In a series of 1632 patients retrieved from our prospectively collected single
      centre SAH database and fulfilling prespecified inclusion criteria, we found 53
      patients with aSDH on the initial CT scan. From the same series, we collected 660
      patients in whom aSDH was ruled out by reviewing the initial CT scan. We compared
      the risk of poor outcome at discharge and at 3 months between patients with and
      without aSDH by calculating crude risk ratios (RRs) with corresponding 95% CIs,
      and adjusting for age, sex, location and treatment modality of the aneurysm that
      bled, clinical condition on admission, intracerebral haemorrhage,
      intraventricular haemorrhage and hydrocephalus, with Poisson regression. RESULTS:
      Patients with aSDH had a higher risk of poor outcome at discharge (crude RR 1.59;
      95% CI 1.35 to 1.86) and at 3 months (crude RR: 2.17, 95% CI 1.79 to 2.62) than
      patients without aSDH. After simultaneous adjustment for five characteristics
      that affected the crude RR, the RR for poor outcome for patients with aSDH at
      discharge was 1.15 (95% CI 0.97 to 1.37) and at 3 months 1.30 (95% CI 1.04 to
      1.62). CONCLUSIONS: The presence of aSDH in patients with aneurysmal SAH is an
      independent risk factor for poor outcome at 3 months.

PMID- 23117496
TI  - Cerebrospinal fluid amyloid-beta and phenotypic heterogeneity in de novo
      Parkinson's disease.
AB  - BACKGROUND: In Parkinson's disease (PD), the motor presentation characterised by
      postural instability/gait difficulties (PIGD) heralds accelerated motor,
      functional and cognitive decline, as compared with the more benign tremor
      dominant (TD) variant. This makes the PIGD complex an attractive target for the
      discovery of prognostic biomarkers in PD. OBJECTIVE: To explore in vivo whether
      variability in brain amyloid-beta (Abeta) metabolism affects the initial motor
      presentation in PD. METHODS: We quantified cerebrospinal fluid (CSF)
      concentrations and ratios of Abeta42, Abeta40 and Abeta38 using a triplex
      immunoassay in 99 patients with de novo PD with the PIGD phenotype (n=39) or the
      TD phenotype (n=60). All patients underwent standardised assessments of motor and
      neuropsychological function and cerebral MRI. 46 age-matched normal controls
      served as external reference. RESULTS: Patients with PD with the PIGD phenotype
      had significantly reduced CSF Abeta42, Abeta38, Abeta42/40 and Abeta38/40 levels
      compared with patients with the TD phenotype and controls. CSF marker levels in
      patients with PD-TD did not differ from those in controls. Multivariate
      regression models demonstrated significant associations of CSF Abeta markers with
      severity of PIGD and lower limb bradykinesia in patients with PD, independently
      from age, MRI white matter hyperintensities and cognition. No associations were
      found between CSF markers and other motor features. CONCLUSIONS: Motor
      heterogeneity in de novo PD independently relates to CSF Abeta markers, with low
      levels found in patients with the PIGD presentation. This suggests that disturbed
      Abeta metabolism has an effect on PD beyond cognition and may contribute to the
      variable rate of motor and functional decline in PD.

PMID- 23117497
TI  - Isolated myositis of the superior oblique muscle.

PMID- 23117498
TI  - Predicting independent survival after stroke: a European study for the
      development and validation of standardised stroke scales and prediction models of
      outcome.
AB  - BACKGROUND: Accurate prediction of stroke outcome is desirable for clinical
      management and provision of appropriate care, and potentially for stratification
      of patients into studies. OBJECTIVES: To investigate the predictive properties of
      validated scales and severity measures, and their constituent variables, and to
      compare their prediction in six European populations. METHODS: We studied 2033
      first-ever stroke patients in population-based stroke registers in France, Italy,
      Lithuania, the UK, Spain and Poland. Logistic models were used to predict
      independent survival at 3 and 12 months after stroke using a range of measures
      including the Six Simple Variable (SSV), Barthel index (BI) and the National
      Institute of Heath Stroke Scale (NIHSS). Predictions were compared within and
      between populations using receiver operating characteristic curves. A five
      variable scale was developed and validated. RESULTS: Comparisons of BI with
      BI+age, and NIHSS with NIHSS+age, across populations showed that inclusion of age
      significantly improved prediction. Fairly equal predictions were obtained by
      three models: five variables, BI+age, and NIHSS+age. Better agreement between
      predicted and actual outcomes, and more precise estimates were obtained by the
      five variables model (age, verbal component of the Glasgow Coma Scale, arm power,
      ability to walk, and pre-stroke dependency). CONCLUSIONS: Living alone before the
      stroke was not significantly associated with independent survival after the
      stroke. Five variables (excluding living alone, from the SSV) provided good
      prediction for all populations and subgroups. Further external validation for our
      estimates is recommended before utilisation of the model in practice and
      research.

PMID- 23117499
TI  - Exact formulas for the variance of several balance indices under the Yule model.
AB  - One of the main applications of balance indices is in tests of nullmodels of
      evolutionary processes. The knowledge of an exact formula for a statistic of a
      balance index, holding for any number n of leaves, is necessary in order to use
      this statistic in tests of this kind involving trees of any size. In this paper
      we obtain exact formulas for the variance under the Yule model of the Sackin, the
      Colless and the total cophenetic indices of binary rooted phylogenetic trees with
      n leaves.

PMID- 23117501
TI  - Transmission of risk-group specific HIV-1 strains among Dutch drug users for more
      than 20 years and their replacement by nonspecific strains after switching to low
      harm drug practices.
AB  - OBJECTIVES: To characterize HIV-1 epidemiological networks of men having sex with
      men (MSM) and drug users (DUs) in the Netherlands for >30 years. DESIGN AND
      METHODS: Previously, we demonstrated different origin of the HIV-1 epidemics in
      Dutch MSM and DUs. To achieve the study objectives, risk group-specific genetic
      markers in the pol gene were examined in 315 participants of the Amsterdam Cohort
      Studies on HIV/AIDS who were registered as HIV-1 infected in 1981-2011. RESULTS:
      Phylogenetic analysis demonstrated circulation of distinct virus strains in the 2
      networks, with 98% of viruses of MSM clustering together and apart from strains
      of 73% DUs. Nine genetic markers that significantly distinguished virus strains
      specific for DUs were identified, of which 3 were >=90% conserved. Over the total
      observation period, only 6% of viruses (4 of MSM and 14 of DUs) clustered with
      those of the other risk group. Among these sequences, the 3 most conserved
      genetic markers of that other risk group were 87% conserved.All 4 cases of DU
      specific viruses among MSM occurred in 1980s-early 1990s. Viruses nonspecific for
      DUs were causing new infections among DUs at the rate of 20% till 2002 and
      replaced DU-specific strains among new infections thereafter, coinciding with
      switching of DUs to low-harm drug practices. CONCLUSIONS: Dutch MSM and DUs have
      remained separate epidemiological networks for decades, despite their
      geographical and behavioral overlap. Switching to low-harm drug practices among
      DUs resulted in new infections caused by HIV-1 strains originating from other
      risk groups.

PMID- 23117500
TI  - HIV testing and counseling leads to immediate consistent condom use among South
      African stable HIV-discordant couples.
AB  - OBJECTIVE: Effective behavioral HIV prevention is needed for stable HIV
      discordant couples at risk for HIV, especially those without access to biomedical
      prevention. This analysis addressed whether HIV testing and counseling with
      ongoing counseling and condom distribution lead to reduced unprotected sex in HIV
      discordant couples. METHODS: Partners in Prevention HSV/HIV Transmission Study
      was a randomized trial conducted from 2004 to 2008 assessing whether acyclovir
      reduced HIV transmission from HSV-2/HIV-1-coinfected persons to HIV-uninfected
      sex partners. This analysis relied on self-reported behavioral data from 508 HIV
      infected South African participants. The exposure was timing of first HIV testing
      and counseling: 0-7, 8-14, 15-30, or >30 days before baseline. In each exposure
      group, predicted probabilities of unprotected sex in the last month were
      calculated at baseline, month 1, and month 12 using generalized estimating
      equations with a logit link and exchangeable correlation matrix. RESULTS: At
      baseline, participants who knew their HIV status for less time experienced higher
      predicted probabilities of unprotected sex in the last month: 0-7 days, 0.71; 8
      14 days, 0.52; 15-30 days, 0.49; >30 days, 0.26. At month 1, once all
      participants had been aware of being in HIV-discordant relationships for >=1
      month, predicted probabilities declined: 0-7 days, 0.08; 8-14 days, 0.08; 15-30
      days, 0.15; >30 days, 0.14. Lower predicted probabilities were sustained through
      month 12: 0-7 days, 0.08; 8-14 days, 0.11; 15-30 days, 0.05; >30 days, 0.19.
      CONCLUSIONS: Unprotected sex declined after HIV-positive diagnosis and declined
      further after awareness of HIV discordance. Identifying HIV-discordant couples
      for behavioral prevention is important for reducing HIV transmission risk.

PMID- 23117502
TI  - Poor diet quality is associated with low CD4 count and anemia and predicts
      mortality among antiretroviral therapy-naive HIV-positive adults in Uganda.
AB  - BACKGROUND: We assessed the association between dietary diversity and CD4 count,
      moderate anemia, and mortality among 876 antiretroviral therapy-naive people
      living with HIV/AIDS infection (PLHIV) in Uganda. METHODS: Participants were
      interviewed and followed for an average of 21.6 months. Dietary diversity was
      measured using the Individual Dietary Diversity Score (IDDS) (range, 0-12) and
      summarized into an overall measure and disaggregated into nutrient-rich food
      groups (range, 0-7), cereals, roots, and tubers (range, 0?x{2013} 2); and oils,
      fats, sugars, and condiments (range, 0?x{2013} 3). We determined the cross
      sectional associations between dietary diversity and (1) immunosuppression (CD4
      count <= 350 cells/MUL) and (2) moderate anemia (hemoglobin < 10 g/dL) at
      baseline with logistic regression. We assessed the association between IDDS and
      mortality using Cox proportional hazards regression. RESULTS: The mean IDDS score
      was 6.3 (SD 1.7) food groups per day, with a mean of 2.7 (SD 1.1) nutrient-rich
      food groups per day. Each additional nutrient-rich food group consumed was
      associated with a 16% reduction in the likelihood of having a CD4 count <=350
      cells/MUL [adjusted odds ratio, 0.84; 95% confidence interval (CI): 0.72 to 0.97]
      at baseline. Among those with >350 CD4 cells per microliter, but not those with
      CD4 count <=350 cells per microliter, consumption of nutrient-rich food groups
      was associated with a lower odds of moderate anemia (adjusted odds ratio, 0.57;
      95% CI: 0.34 to 0.96). During follow-up, 48 participants (5.6%) died (mortality
      rate of 3.1 per 100 person-years). IDDS was inversely associated with mortality
      [adjusted hazard ratio, 0.76; 95% CI: 0.63 to 0.91]. CONCLUSION: These results
      suggest that diet quality is an important determinant of HIV disease severity and
      mortality in antiretroviral therapy-naive PLHIV.

PMID- 23117506
TI  - E-health and the transformation of mental health care.

PMID- 23117503
TI  - Leveraging a rapid, round-the-clock HIV testing system to screen for acute HIV
      infection in a large urban public medical center.
AB  - OBJECTIVE: To describe the prevalence and location of new and acute HIV diagnoses
      in a large urban medical center. Secondary objectives were to evaluate rapid HIV
      test performance, the added yield of acute HIV screening, and linkage-to-care
      outcomes. DESIGN: Cross-sectional study from November 1, 2008, to April 30, 2009.
      METHODS: The hospital laboratory performed round-the-clock rapid HIV antibody
      testing on venipuncture specimens from patients undergoing HIV testing in
      hospital and community clinics, inpatient settings, and the emergency department
      (ED). For patients with negative results, a public health laboratory conducted
      pooled HIV RNA testing for acute HIV infection. The laboratories communicated
      positive results from the hospital campus to a linkage team. Linkage was defined
      as 1 outpatient HIV-related visit. RESULTS: Among 7927 patients, 8550 rapid tests
      resulted in 137 cases of HIV infection [1.7%, 95% confidence interval (CI): 1.5%
      to 2.0%], of whom 46 were new HIV diagnoses (0.58%, 95% CI: 0.43% to 0.77%).
      Pooled HIV RNA testing of 6704 specimens (78.4%) resulted in 3 cases of acute HIV
      infection (0.05%, 95% CI: 0.01% to 0.14%) and increased HIV case detection by
      3.5%. Half of new HIV diagnoses and two thirds of acute infections were detected
      in the ED and urgent care clinic. Rapid test sensitivity was 98.9% (95% CI: 93.8%
      to 99.8%) and the specificity 99.9% (95% CI: 99.7% to 99.9%). More than 95% of
      newly diagnosed and out-of-care HIV-infected patients were linked to care.
      CONCLUSIONS: Patients undergoing HIV testing in EDs and urgent care clinics may
      benefit from being simultaneously screened for acute HIV infection.

PMID- 23117504
TI  - Risk of virological failure and drug resistance during first and second-line
      antiretroviral therapy in a 10-year cohort in Senegal: results from the ANRS 1215
      cohort.
AB  - BACKGROUND: In 1998, Senegal launched one of Africa's first antiretroviral
      therapy (ART) programs. Since then, the number of treated patients in Africa has
      substantially increased thanks to simplification in treatment management.
      Although good outcomes over the first years of ART have been observed in sub
      Saharan Africa, little is known about the long-term (>5 years) risks of
      virological failure and drug resistance and about second-line treatment response.
      METHODS: Patients from the ANRS-1215 cohort in Senegal, started with either one
      nonnucleoside reverse transcriptase inhibitor or indinavir, a first-generation
      nonboosted protease inhibitor, followed for >6 months and having >1 viral load
      (VL) measurement were included. Virological failure was defined as 2 consecutive
      VL measurements >1000 copies/mL. RESULTS: Of the 366 patients included, 89%
      achieved a VL <500 copies/mL. The risk of virological failure at 12, 24, and 60
      months was 5%, 16%, and 25%, being higher in younger patients (P = 0.05), those
      receiving a protease inhibitor-containing regimen (P = 0.05), and those with
      lower adherence (P = 0.03). The risk of resistance to any drug at 12, 24, and 60
      months was 3%, 11%, and 18%. After virological failure, 60% of the patients were
      switched to second-line treatments. Although 81% of the patients achieved
      virological success, the risk of virological failure was 27% at 24 months, mostly
      in patients with multiple resistances. CONCLUSIONS: In this cohort, virological
      outcomes for first-line treatments were good compared with those from high
      resource settings. However, the rate of virological failure for second-line
      treatment was high, probably because of accumulation of resistances.

PMID- 23117509
TI  - Identifying priorities for patient-centered outcomes research for serious mental
      illness.
AB  - OBJECTIVE: The purpose of this project was to engage a diverse group of
      stakeholders (N=38) to help establish priorities to guide patient-centered
      outcomes research (PCOR) in serious mental illness. METHODS: Three meetings, two
      Web-based and one on site, were held to generate and prioritize an initial list
      of topics. Topics were then sorted and organized into common themes. RESULTS:
      About 140 topics were identified and sorted into 21 main themes, ranked by
      priority. Three of the top four themes focused on how research was conducted,
      particularly the need to develop consensus measurement and outcomes definitions;
      improving infrastructure for research, longitudinal studies, and new data sets
      and investigators; and developing PCOR methodology. Stakeholders also identified
      a need to focus on service delivery, treatment settings, and structure of the
      delivery of care. CONCLUSIONS: Engagement by a broad group of stakeholders in a
      transparent process resulted in the identification of priority areas for PCOR.
      Stakeholders clearly indicated a need to fundamentally change how research on
      serious mental illness is conducted and a critical need for the development of
      methodology and infrastructure. Most current PCOR has been focused on relatively
      short-term outcomes, but real world, long-term studies providing guidance for
      treatment over the lifetime of a serious mental illness are needed.

PMID- 23117510
TI  - A description of telemental health services provided by the Veterans Health
      Administration in 2006-2010.
AB  - OBJECTIVE: This is the first large-scale study to describe the types of
      telemental health services provided by the Veterans Health Administration (VHA).
      METHODS: The authors compiled national-level VHA administrative data for fiscal
      years 2006-2010 (October 1, 2005, to September 30, 2010). Telemental health
      encounters were identified by VHA and U.S. Department of Veterans Affairs stop
      codes and categorized as medication management, individual psychotherapy with or
      without medication management, group psychotherapy, and diagnostic assessment.
      RESULTS: A total of 342,288 telemental health encounters were identified, and
      each type increased substantially across the five years. Telepsychotherapy with
      medication management was the fastest growing type of telemental health service.
      CONCLUSIONS: The use of videoconferencing technology has expanded beyond
      medication management alone to include telepsychotherapy services, including both
      individual and group psychotherapy, and diagnostic assessments. The increase in
      telemental health services is encouraging, given the large number of returning
      veterans living in rural areas.

PMID- 23117511
TI  - Complementary and alternative medicine in VA specialized PTSD treatment programs.
AB  - OBJECTIVE: This survey documented the provision of complementary and alternative
      medicine (CAM) treatments in U.S. Department of Veterans Affairs (VA) specialized
      posttraumatic stress disorder (PTSD) treatment programs. METHODS: Program
      coordinators or designated staff from 125 of 170 VA specialized PTSD treatment
      programs completed and returned surveys between September 2010 and March 2011,
      indicating which of 32 CAM treatments were offered in that program. RESULTS:
      Ninety-six percent of programs reported use of at least one CAM treatment. Eighty
      eight percent offered CAMs other than those that are commonly part of
      conventional PTSD treatments (guided imagery, progressive muscle relaxation, and
      stress management-relaxation therapies). CONCLUSIONS: The widespread use of CAM
      treatments in VA PTSD programs presents an opportunity for researchers to assess
      the effect of CAM on mental health service use and PTSD symptoms among veterans.
      Future research should assess the effectiveness of CAM treatments and develop
      methods to tailor these treatments to veterans with PTSD.

PMID- 23117512
TI  - VA primary care-mental health integration: patient characteristics and receipt of
      mental health services, 2008-2010.
AB  - OBJECTIVE: In 2007, the U.S. Department of Veterans Affairs (VA) health system
      began nationwide implementation of primary care-mental health integration (PC
      MHI) programs to enhance mental health access and promote treatment of common
      mental health conditions for patients in primary care settings. This report
      describes patients initiating PC-MHI services in fiscal years (FYs) 2008-2010,
      including those who received prior mental health services. METHODS: Using VA
      administrative records, the investigators examined characteristics and services
      utilization of individuals who initiated PC-MHI services in FY 2008 (N=76,985),
      FY 2009 (N=107,417), or FY 2010 (N=149,938). RESULTS: PC-MHI service initiation
      increased by 95%, from 76,985 to 149,938 veterans. Over time, new user cohorts
      were increasingly younger, newer to VA services, and less likely to have received
      VA mental health treatment in the prior year. CONCLUSIONS: This study documents
      substantial expansion in VA PC-MHI program activity. PC-MHI program expansion may
      increase access to mental health services in primary care settings.

PMID- 23117513
TI  - Integrated care, recovery-consistent care features, and quality of life for
      patients with serious mental illness.
AB  - OBJECTIVE: The goal of this study was to evaluate relationships between recovery
      supportive and integrated care features with health-related quality of life for
      veterans with serious mental illness. METHODS: Data were utilized from several
      national Veterans Affairs (VA) databases for 2,394 patients with serious mental
      illness from 107 VA sites. Regressions evaluated relationships between health
      related quality of life and care features. RESULTS: Higher quality of life in
      regard to general health was associated with sites that offered peer support
      (beta=1.79, p<.01) and with patients' increased understanding of their treatment
      (beta=.80, p<.01), whereas lower quality of life was associated with sites with
      colocated general medical and mental health care providers (beta=-1.37, p<.05)
      and family psychoeducation (beta=-1.41, p<.05). Care at sites with vocational
      rehabilitation (beta=1.38, p<.05), peer support (beta=1.85, p<.05), and colocated
      providers (beta=1.60, p<.05) and patients' increased understanding of care
      (beta=.82, p<.01) were all associated with increased mental health quality of
      life, whereas reduced mental health quality of life was associated with care at
      sites with social skills training (beta=-1.48, p<.05) or increased levels of care
      collaboration between primary care and mental health providers (beta=-.27,
      p<.01). CONCLUSIONS: Recovery-oriented care might be associated with increased
      health-related quality of life among patients with serious mental illness.

PMID- 23117514
TI  - Factors associated with initiation on clozapine and on other antipsychotics among
      Medicaid enrollees.
AB  - OBJECTIVE: Demographic and clinical factors associated with starting clozapine
      and other antipsychotics were examined. METHODS: New York State Medicaid claims
      from 2008 to 2009 identified individuals with a schizophrenia spectrum disorder,
      continuous Medicaid eligibility during the study, and at least one clinic service
      and antipsychotic fill. The sample included individuals who initiated an
      antipsychotic without any fills for the same medication in the prior 90 days
      (N=7,035). RESULTS: Only 144 patients (2%) started on clozapine. They were more
      likely to be younger, white males who had received services in a state-operated
      facility, with more hospital admissions and higher total psychiatric costs.
      African Americans and Hispanics were less likely than whites to start on
      clozapine. Individuals with substance use disorders were less likely than those
      without them to start on clozapine. CONCLUSIONS: Clozapine was rarely prescribed,
      and problematic disparities were found. Quality improvement efforts are needed to
      ensure that patients are offered this effective treatment when appropriate.

PMID- 23117515
TI  - Relationship between ambient temperature and humidity and visits to mental health
      emergency departments in Quebec.
AB  - OBJECTIVE: This study examined whether the number of emergency department visits
      for "mental and psychosocial problems" varies with temperature or humidity.
      METHODS: The number of visits in three geographic areas of Quebec were examined
      as a function of temperature and humidity by using routinely collected May
      September data for 1995-2007 (N=347,552 visits). Data for two age groups (under
      age 65 and age 65 and older) were examined. Incidence rate ratios for mean
      temperature and humidity were estimated by using Poisson regression and
      generalized additive models. RESULTS: The number of visits tended to increase
      with increasing mean temperature. At 22.5  degrees C (72.5  degrees F) and 25 
      degrees C (77.0  degrees F), the number was usually significantly higher than
      average. Visits increased with humidity in the younger age group. CONCLUSIONS:
      Results suggest increased use of emergency departments for mental and
      psychosocial problems with higher mean temperature and humidity, especially in
      metropolitan areas and in southern Quebec. Climate change may make this effect
      increasingly important.

PMID- 23117516
TI  - Adventure camps for young adults and adults with mental illness.

PMID- 23117517
TI  - Report on parents with disabilities highlights pervasive prejudices.

PMID- 23117519
TI  - Integrative medicine improves mood in an inpatient setting.

PMID- 23117520
TI  - IOM report highlights health system inefficiencies.

PMID- 23117522
TI  - Continuous fill intermittent decant type sequencing batch reactor application to
      upgrade the UASB treated sewage.
AB  - The performance of continuous flow intermittent decant type sequencing batch
      (CFID) reactor treating the effluent of an UASB reactor treating domestic
      wastewater and operated at 8 h hydraulic retention time (HRT) was investigated.
      The CFID was operated at three different HRTs (22, 8 and 6 h) and three different
      dissolved oxygen (DO) patterns (<0.5, 2.5-3.5 and 3.5-4.5 mg/L). The highest
      effluent quality was observed at the 8 h HRT and 2.5-3.5 mg/L DO concentration.
      At this operational condition, the average BOD, TSS, ammonia nitrogen and fecal
      coliform removal efficiencies were 83, 90, 74 and 99 %, respectively. The CFID is
      a promising post-treatment option for existing UASB systems, with a final
      effluent quality that comply with receiving water and effluent reuse criteria.

PMID- 23117521
TI  - PET/SPECT imaging of hindlimb ischemia: focusing on angiogenesis and blood flow.
AB  - Peripheral artery disease (PAD) is a result of the atherosclerotic narrowing of
      blood vessels to the extremities, and the subsequent tissue ischemia can lead to
      the up-regulation of angiogenic growth factors and formation of new vessels as a
      recovery mechanism. Such formation of new vessels can be evaluated with various
      non-invasive molecular imaging techniques, where serial images from the same
      subjects can be obtained to allow the documentation of disease progression and
      therapeutic response. The most commonly used animal model for preclinical studies
      of PAD is the murine hindlimb ischemia model, and a number of radiotracers have
      been investigated for positron emission tomography (PET) and single photon
      emission computed tomography (SPECT) imaging of PAD. In this review article, we
      summarize the PET/SPECT tracers that have been tested in the murine hindlimb
      ischemia model as well as those used clinically to assess the extremity blood
      flow.

PMID- 23117533
TI  - A chitosan based, laser activated thin film surgical adhesive, 'SurgiLux':
      preparation and demonstration.
AB  - Sutures are a 4,000 year old technology that remain the 'gold-standard' for wound
      closure by virtue of their repair strength (~100 KPa). However, sutures can act
      as a nidus for infection and in many procedures are unable to effect wound repair
      or interfere with functional tissue regeneration.(1) Surgical glues and
      adhesives, such as those based on fibrin and cyanoacrylates, have been developed
      as alternatives to sutures for the repair of such wounds. However, current
      commercial adhesives also have significant disadvantages, ranging from viral and
      prion transfer and a lack of repair strength as with the fibrin glues, to tissue
      toxicity and a lack of biocompatibility for the cyanoacrylate based adhesives.
      Furthermore, currently available surgical adhesives tend to be gel-based and can
      have extended curing times which limit their application.(2) Similarly, the use
      of UV lasers to facilitate cross-linking mechanisms in protein-based or albumin
      'solders' can lead to DNA damage while laser tissue welding (LTW) predisposes
      thermal damage to tissues.(3) Despite their disadvantages, adhesives and LTW have
      captured approximately 30% of the wound closure market reported to be in excess
      of US $5 billion per annum, a significant testament to the need for sutureless
      technology.(4) In the pursuit of sutureless technology we have utilized chitosan
      as a biomaterial for the development of a flexible, thin film, laser-activated
      surgical adhesive termed 'SurgiLux'. This novel bioadhesive uses a unique
      combination of biomaterials and photonics that are FDA approved and successfully
      used in a variety of biomedical applications and products. SurgiLux overcomes all
      the disadvantages associated with sutures and current surgical adhesives (see
      Table 1). In this presentation we report the relatively simple protocol for the
      fabrication of SurgiLux and demonstrate its laser activation and tissue weld
      strength. SurgiLux films adhere to collagenous tissue without chemical
      modification such as cross-linking and through irradiation using a comparatively
      low-powered (120 mW) infrared laser instead of UV light. Chitosan films have a
      natural but weak adhesive attraction to collagen (~3 KPa), laser activation of
      the chitosan based SurgiLux films emphasizes the strength of this adhesion
      through polymer chain interactions as a consequence of transient thermal
      expansion.(5) Without this 'activation' process, SurgiLux films are readily
      removed.(6-9) SurgiLux has been tested both in vitro and in vivo on a variety of
      tissues including nerve, intestine, dura mater and cornea. In all cases it
      demonstrated good biocompatibility and negligible thermal damage as a consequence
      of irradiation.(6-10).

PMID- 23117534
TI  - Surface tension confined (STC) tracks for capillary-driven transport of low
      surface tension liquids.
AB  - Surface tension confined (STC) open tracks for pumpless transport of low-surface
      tension liquids (e.g., acetone, ethanol, hexadecane) on microfluidic chips are
      fabricated using a large-area, wet-processing technique. Wettable, paraffin-wax,
      submillimeter-wide tracks are applied by a fountain-pen procedure on
      superoleophobic, fluoroacrylic-carbon nanofiber (CNF) composite coatings. The
      fabricated anisotropic wetting patterns confine the low-surface-tension liquids
      onto the flow tracks, driving them with meniscus velocities up to 3.1 cm s(-1).
      Scaling arguments and Washburn's equation provide estimates of the liquid
      velocities measured in the STC tracks. These tracks are also shown to act as
      rails for directional sliding control of mm-sized water droplets. The present
      facile top-down patterned wettability approach can be extended to deposit
      micrometer-wide tracks, which bear promise for pumpless handling of low-surface
      tension liquids (e.g., aqueous solutions containing alcohols or surfactants) in
      lab-on-a-chip type applications or in low power, high-throughput bio
      microfluidics for health care applications.

PMID- 23117535
TI  - Noise sensitivity and multiple chemical sensitivity scales: properties in a
      population based epidemiological study.
AB  - Noise sensitivity is considered to be a self-perceived indicator of vulnerability
      to stressors in general and not noise alone. Multiple chemical sensitivity (MCS)
      has to some extent been accompanied by noise sensitivity, indicating a moderate
      correspondence between them. The aim of this study is to investigate if the
      Weinstein's Noise Sensitivity Scale and Quick Environmental Exposure and
      Sensitivity Inventory's (QEESI) Chemical Intolerance Subscale can differentiate
      noise sensitivity and MCS as different entities, and if there are overlaps in the
      characteristics of noise sensitivity and MCS. In 2002, 327 individuals (166 men,
      161 women; age range 45 - 66 years) from the Finnish Twin Cohort answered a
      questionnaire on noise-related and MCS items. Somatic, psychological, and
      lifestyle factors were obtained through earlier questionnaires for the same
      individuals. Both confirmatory and exploratory factor analyses (CFA and EFA) of
      the questionnaire items on the Weinstein's Noise Sensitivity Scale and QEESI's
      Chemical Intolerance Subscale indicated the presence of three factors - Noise
      Sensitivity, Chemical Sensitivity, and Ability to Concentrate factors - arising
      from the forming of two factors from the items of the Weinstein's scale. In the
      regression analyses, among all subjects, the Noise Sensitivity Factor was
      associated with neuroticism and smoking, and the Chemical Sensitivity Factor was
      associated with allergies and alcohol use. The study indicates that the
      Weinstein's Noise Sensitivity Scale and QEESI's Chemical Intolerance Subscale
      differentiate noise sensitivity and MCS as different entities.

PMID- 23117536
TI  - Noise impacts from professional dog grooming forced-air dryers.
AB  - This study was designed to measure the sound output of four commonly used brands
      of forced-air dryers used by dog groomers in the United States. Many dog groomers
      have questions about the effect of this exposure on their hearing, as well as on
      the hearing of the dogs that are being groomed. Readings taken from each dryer at
      1 meter (the likely distance of the dryer from the groomer and the dog) showed
      average levels ranging from 105.5 to 108.3 dB SPL or 94.8 to 108.0 dBA. Using the
      90 dBA criterion required by the US Occupational Safety and Health
      Administration, dog groomers/bathers are at risk if exposure to the lowest
      intensity dryer (94.8 dBA) exceeds 4 hours per day. If the more stringent 85 dBA
      criterion and 3 dB tradeoff is applied, less than one hour of exposure is
      permissible in an 8 hour day. Cautions are recommended for any persons exposed to
      noise from forced-air dryers.

PMID- 23117537
TI  - Exposure to industrial wideband noise increases connective tissue in the rat
      liver.
AB  - Rats were daily exposed (eight hours/day) for a period of four weeks to the same
      high-intensity wideband noise that was recorded before in a large textile plant.
      Histologic observation of liver sections of the rats was used to perform
      quantitative comparison of hepatic connective tissue (dyed by Masson trichromic
      staining) between the noise-exposed and control animals. For that, we have
      photographed at random centrolobular areas of stained rat liver sections. We
      found that noise exposure resulted in significant enhancement in the area of
      collagen-rich connective tissue present in the centrolobular domain of the rat
      liver. Our data strengthen previous evidence showing that fibrotic transformation
      is a systemic effect of chronic exposure of rodents and humans to industrial
      wideband noise.

PMID- 23117538
TI  - The acoustic environment of intensive care wards based on long period nocturnal
      measurements.
AB  - The patients in the Intensive Care Units are often exposed to excessive levels of
      noise and activities. They can suffer from sleep disturbance, especially at
      night, but they are often too ill to cope with the poor environment. This article
      investigates the acoustic environment of typical intensive care wards in the UK,
      based on long period nocturnal measurements, and examines the differences between
      singlebed and multibed wards, using statistical analysis. It has been shown that
      the acoustic environment differs significantly every night. There are also
      significant differences between the noise levels in the singlebed and multibed
      wards, where acoustic ceilings are present. Despite the similar background noises
      in both ward types, more intrusive noises tend to originate from the multibed
      wards, while more extreme sounds are likely to occur in the single wards. The
      sound levels in the measured wards for each night are in excess of the World
      Health Organization's (WHO) guide levels by at least 20 dBA, dominantly at the
      middle frequencies. Although the sound level at night varies less than that in
      the daytime, the nocturnal acoustic environment is not dependant on any specific
      time, thus neither the noisiest nor quietest period can be determined. It is
      expected that the statistical analysis of the collected data will provide
      essential information for the development of relevant guidelines and noise
      reduction strategies.

PMID- 23117539
TI  - Effects of industrial wind turbine noise on sleep and health.
AB  - Industrial wind turbines (IWTs) are a new source of noise in previously quiet
      rural environments. Environmental noise is a public health concern, of which
      sleep disruption is a major factor. To compare sleep and general health outcomes
      between participants living close to IWTs and those living further away from
      them, participants living between 375 and 1400 m (n = 38) and 3.3 and 6.6 km (n =
      41) from IWTs were enrolled in a stratified cross-sectional study involving two
      rural sites. Validated questionnaires were used to collect information on sleep
      quality (Pittsburgh Sleep Quality Index - PSQI), daytime sleepiness (Epworth
      Sleepiness Score - ESS), and general health (SF36v2), together with psychiatric
      disorders, attitude, and demographics. Descriptive and multivariate analyses were
      performed to investigate the effect of the main exposure variable of interest
      (distance to the nearest IWT) on various health outcome measures. Participants
      living within 1.4 km of an IWT had worse sleep, were sleepier during the day, and
      had worse SF36 Mental Component Scores compared to those living further than 1.4
      km away. Significant dose-response relationships between PSQI, ESS, SF36 Mental
      Component Score, and log-distance to the nearest IWT were identified after
      controlling for gender, age, and household clustering. The adverse event reports
      of sleep disturbance and ill health by those living close to IWTs are supported.

PMID- 23117540
TI  - The impact of aircraft noise exposure on South African children's reading
      comprehension: the moderating effect of home language.
AB  - Given the limited studies conducted within the African continent, the purpose of
      this study was to investigate the impact of chronic aircraft noise exposure and
      the moderating effect of home language on the learners' reading comprehension.
      The sample comprised 437 (52%) senior primary learners exposed to high levels of
      aircraft noise (Experimental group) and 337 (48%) learners residing in a quieter
      area (Control group). Of these, 151 learners in the Experimental group spoke
      English as a first language (EFL) and 162 spoke English as a second language
      (ESL). In the Control group, the numbers were similarly divided (EFL n = 191; ESL
      n = 156). A univariate General Linear Model was used to investigate the effects
      of aircraft noise exposure and language on reading comprehension, while observing
      for the possible impact of intellectual ability, gender, and socioeconomic status
      on the results. A significant difference was observed between ESL and EFL
      learners in favor of the latter (F 1,419 = 21.95, P =.000). In addition a
      substantial and significant interaction effect was found between the experimental
      and control groups for the two language groups. For the EFL speakers there was a
      strong reduction in reading comprehension in the aircraft noise group. By
      contrast this difference was not significant for the ESL speakers. Implications
      of the findings and suggestions for further research are made in the article.

PMID- 23117541
TI  - EchoScan: a new system to objectively assess peripheral hearing disorders.
AB  - Pure-tone air-conduction audiometry (PTA) is the reference clinical test used in
      Europe and the United States to measure the extent of hearing loss. It is a
      subjective, behavioral test, which measures thresholds of hearing sensations and
      perceptions based on patient responses to frequency-specific pure-tone stimuli.
      PTA can detect hearing problems due to cochlear or retro-cochlear impairment,
      without identifying the source of the problem. In contrast, cubic distortion
      product otoacoustic emissions (DPOAEs) detect inner-ear dysfunctions,
      particularly those involving the outer hair cells sensitive to noise and
      ototoxicants. Recently, ototoxicants were shown to have an action on the central
      nuclei driving the middle-ear acoustic reflex. Therefore, a new device, called
      EchoScan, was conceived to collect and measure performance both in the middle-
      and inner-ear. Its originality: the use of a battery of DPOAE measurements
      associated with contra-lateral acoustic stimulation. Changes in DPOAE amplitude
      due to ageing and gender were incidentally detected and EchoScan was more
      sensitive than impedancemetry to detect the stapedial reflex. EchoScan can be
      used both in clinical investigations and in occupational medicine, especially for
      the auditory follow-up of people exposed to noise or ototoxic agents. EchoScan
      could be promising to assess early detection in programs to prevent hearing loss.

PMID- 23117542
TI  - Performance, fatigue and stress in open-plan offices: the effects of noise and
      restoration on hearing impaired and normal hearing individuals.
AB  - Hearing impaired and normal hearing individuals were compared in two within
      participant office noise conditions (high noise: 60 L Aeq and low noise: 30 L Aeq
      ). Performance, subjective fatigue, and physiological stress were tested during
      working on a simulated open-plan office. We also tested two between-participants
      restoration conditions following the work period with high noise (nature movie or
      continued office noise). Participants with a hearing impairment (N = 20) were
      matched with normal hearing participants (N = 18) and undertook one practice
      session and two counterbalanced experimental sessions. In each experimental
      session they worked for two hours with basic memory and attention tasks. We also
      measured physiological stress indicators (cortisol and catecholamines) and self
      reports of mood and fatigue. The hearing impaired participants were more affected
      by high noise than the normal hearing participants, as shown by impaired
      performance for tasks that involve recall of semantic information. The hearing
      impaired participants were also more fatigued by high noise exposure than
      participants with normal hearing, and they tended to have higher stress hormone
      levels during the high noise compared to the low noise condition. Restoration
      with a movie increased performance and motivation for the normal hearing
      participants, while rest with continued noise did not. For the hearing impaired
      participants, continued noise during rest increased motivation and performance,
      while the movie did not. In summary, the impact of noise and restorative
      conditions varied with the hearing characteristics of the participants. The small
      sample size does however encourage caution when interpreting the results.

PMID- 23117543
TI  - Comparative assessment of 5' A/T-rich overhang sequences with optimal and sub
      optimal primers to increase PCR yields and sensitivity.
AB  - Efficient PCR amplifications require precisely designed and optimized
      oligonucleotide primers, components, and cycling conditions. Despite recent
      software development and reaction improvement, primer design can still be
      enhanced. The aims of this research are to understand (1) the effect on PCR
      efficiency and DNA yields of primer thermodynamics parameters, and (2) the
      incorporation of 5' A/T-rich overhanging sequences (flaps) during primer design.
      Two primer sets, one optimal (DeltaG = 0) and one sub-optimal (DeltaG = 0.9),
      were designed using web interface software Primer3, BLASTn, and mFold to target a
      movement protein gene of Tobacco mosaic virus. The optimal primer set amplifies a
      product of 195 bp and supports higher PCR sensitivity and yields compared to the
      sub-optimal primer set, which amplifies a product of 192 bp. Greater fluorescence
      was obtained using optimal primers compared to that with sub-optimal primers.
      Primers designed with sub-optimal thermodynamics can be substantially improved by
      adding 5' flaps. Results indicate that even if the performance of some primers
      can be improved substantially by 5' flap addition, not all primers will be
      similarly improved. Optimal 5' flap sequences are dependent on the primer
      sequences, and alter the primer's T m value. The manipulation of this feature may
      enhance primer's efficiency to increase the PCR sensitivity and DNA yield. 

PMID- 23117545
TI  - Electromerism and linkage isomerism in biologically-relevant Fe-SO complexes.
AB  - Sulfur monoxide, SO, is a relatively unstable molecule whose metal-coordinating
      properties have received little attention in bioinorganic chemistry. Reported
      here is a density functional theory (DFT) examination of the four possible
      oxidation states for a heme-SO/OS adduct previously proposed to be a part of the
      catalytic cycle of sulfite reductases. The FeOS and FeSO isomers are found to be
      degenerate in energy in most cases, suggesting that they both may be observable;
      the FeSO isomers would be the ones more likely to occur during the catalytic
      cycle of sulfite reductases - a cycle which indeed is initiated with the sulfite
      bound to iron via the sulfur, not via the oxygen. More importantly, higher spin
      states tend to be favored especially in the more oxidized models - which are the
      states occurring earlier in the proposed catalytic cycle. This implies weaker
      iron-ligand bonds - and, in fact, in several cases, essentially broken bonds. The
      sulfite reductase active site features an iron-sulfur cluster sharing one of its
      sulfur thiolates with the heme as the axial ligand. This uncommon proximity has
      as unavoidable effect an increase in the efficiency of delivery of electrons to
      the heme once SO has been generated at the active site. This would then allow the
      catalytic cycle to proceed to the next step - exothermic protonation of the SO.

PMID- 23117544
TI  - Cerato-populin and cerato-platanin, two non-catalytic proteins from
      phytopathogenic fungi, interact with hydrophobic inanimate surfaces and leaves.
AB  - Based on sequence homology, several fungal Cys-rich secreted proteins have been
      grouped in the cerato-platanin (CP) family, which comprises at least 40 proteins
      involved mainly in eliciting defense-related responses. The core member of this
      family is cerato-platanin, a moderately hydrophobic protein with a double psi
      beta barrel fold. CP and the recently identified orthologous cerato-populin
      (Pop1) are involved in host-fungus interaction, and can be considered non
      catalytic fungal PAMPs. CP is more active in inducing defense when in an
      aggregated conformation than in its native form, but little is known about other
      CP-orthologous proteins. Here, we cloned, expressed, and purified recombinant
      Pop1, which was used to characterize the protein aggregates. Our results suggest
      that the unfolded, self-assembled Pop1 is more active in inducing defense, and
      that the unfolding process can be induced by interaction with hydrophobic
      inanimate surfaces such as Teflon, treated mica, and gold sheets. In vivo, we
      found that both CP and Pop1 interact with the hydrophobic cuticle of leaves.
      Therefore, we propose that the interaction of these proteins with host cuticle
      waxes could induce unfolding and consequently trigger their PAMP-like activity. 

PMID- 23117546
TI  - Rare double heterozygous mutations in antithrombin underlie hereditary
      thrombophilia in a Chinese family.
AB  - VTE is a complex disorder with two main manifestations: DVT and PE. Deficiency of
      natural anticoagulants plays an important role in the pathogenesis of VTE.
      Antithrombin (AT) deficiency is one of the most common hereditary thrombophilia
      in Asia. Subjects with AT deficiency have two mutations in the same allele of the
      SERPINC1 gene: p.Arg45Gln and p.Ser114Arg (Arg13Gln and Ser82Arg, according to
      the antithrombin mutation database). DNA sequencing, ELISA (enzyme-linked immuno
      sorbent assay), plasmid transfection, and homology modeling were performed to
      study the molecular pathophysiological mechanism of the deficiency. Recombinant
      expression of these mutations demonstrated a relevant functional effect on the
      p.Ser114Arg mutation, since it almost abolished the secretion of AT to the
      conditioned medium and increased intracellular retention, while the p.Arg45Gln
      mutation had negligible effects. Homology modeling showed that some atoms from
      Arg114 interfered with the atoms of the beta-strand, the abstract power between
      Arg45 and S2 was larger than that between Gln45 and S2, and the electrostatic
      energy (-617.281 to -452.079 K) was the primary contributor to this difference.
      The functional mutation responsible for the deficiency of this potent
      anticoagulant p.Ser114Arg probably has conformational consequences on the folding
      of the protein leading to its intracellular accumulation and impaired secretion. 

PMID- 23117547
TI  - Ang II induce kidney damage by recruiting inflammatory cells and up regulates
      PPAR gamma and Renin 1 gene: effect of beta carotene on chronic renal damage.
AB  - Antioxidants are widely used for prevention of diseases associated with oxidative
      stress and ischemic disorder. We investigated the hypothesis of antioxidants
      (alpha-tocopherol and beta-carotene) can suppress the renal disorder in apo E-/
      mice. Renal damage induced by chronic infusion of Angiotensin II (Ang II) into 4
      month old male apo E-/-mice. After that the mice were treated with diet enriched
      alpha tocopherol and beta carotene (800 mg/kg) for 150 days. Ang II treated
      kidney showed polycystic appearance with accumulation of clear fluid and
      constriction of renal artery and renal vein was noticed. Vacuolar/cystic
      degeneration as well as inflammatory reactions was noticed in the
      tubules/glomerulus of Ang II treated mice. beta carotene treated mice showed
      enormous numbers of regenerated tubules in the kidney and over expression of ICAM
      proteins in the regenerated tubules. CD 45.2, MAC 3 proteins were over expressed
      in the inflammatory cells infiltrated into the tubular region of Ang II treated
      kidney. Gene expression studies revealed up regulation of Renin 1 (Ren 1) and
      PPARgamma genes in the kidney of Ang II treated animals, but the beta carotene
      treatment controlled the expression of these genes in the regenerated kidneys.
      beta carotene may have protective effective on chronic renal disorder. It may
      repress the inflammatory genes (Ren 1, PPARgamma) to achieve the protective
      effect on Ang II induced renal damage. 

PMID- 23117548
TI  - WT1, WTX and CTNNB1 mutation analysis in 43 patients with sporadic Wilms' tumor.
AB  - Wilms' tumor (WT) is a heterogeneous neoplasia characterized by a number of
      genetic abnormalities, involving tumor suppressor genes, oncogenes and genes
      related to the Wnt signaling pathway. Somatic biallelic inactivation of WT1 is
      observed in 5-10% of sporadic WT. Somatic mutations in exon 3 of CTNNB1, which
      encodes beta-catenin, were initially observed in 15% of WT. WTX encodes a protein
      that negatively regulates the Wnt/beta-catenin signaling pathway and mediates the
      binding of WT1. In this study, we screened germline and somatic mutations in
      selected regions of WT1, WTX and CTNNB1 in 43 WT patients. Mutation analysis of
      WT1 identified two single-nucleotide polymorphisms, one recurrent nonsense
      mutation (p.R458X) in a patient with proteinuria but without genitourinary
      findings of Denys-Drash syndrome (DDS) and one novel missense mutation, p.C428Y,
      in a patient with Denys-Drash syndrome phenotype. WT1 SNP rs16754A>G (R369R) was
      observed in 17/43 patients, and was not associated with significant difference in
      age at diagnosis distribution, or with 60-month overall survival rate. WTX
      mutation analysis identified five sequence variations, two synonymous
      substitutions (p.Q1019Q and p.D379D), a non-synonymous mutation (p.F159L), one
      frameshift mutation (p.157X) and a novel missense mutation, p.R560W. Two sequence
      variations in CTNNB1 were identified, p.T41A and p.S45C. Overall survival of
      bilateral cases was significantly lower (p=0.005). No difference was observed
      when survival was analyzed among patients with WT1 or with WTX mutations. On the
      other hand, the survival of two patients with the CTNNB1 p.T41A mutation was
      significantly lower (p=0.000517) than the average.

PMID- 23117549
TI  - Virtual and experimental high-throughput screening (HTS) in search of novel
      inosine 5'-monophosphate dehydrogenase II (IMPDH II) inhibitors.
AB  - IMPDH (Inosine 5'-monophosphate dehydrogenase) catalyzes a rate-limiting step in
      the de novo biosynthesis of guanine nucleotides. IMPDH inhibition in sensitive
      cell types (e.g., lymphocytes) blocks proliferation (by blocking RNA and DNA
      synthesis as a result of decreased cellular levels of guanine nucleotides). This
      makes it an interesting target for cancer and autoimmune disorders. Currently
      available IMPDH inhibitors such as mycophenolic acid (MPA, uncompetitive
      inhibitor) and nucleoside analogs (e.g., ribavirin, competitive inhibitor after
      intracellular activation by phosphorylation) have unfavorable tolerability
      profiles which limit their use. Hence, the quest for novel IMPDH inhibitors
      continues. In the present study, a ligand-based virtual screening using IMPDH
      inhibitor pharmacophore models was performed on in-house compound collection. A
      total of 50,000 virtual hits were selected for primary screen using in vitro
      IMPDH II inhibition up to 10 MUM. The list of 2,500 hits (with >70 % inhibition)
      was further subjected to hit confirmation for the determination of IC(50) values.
      The hits obtained were further clustered using maximum common substructure based
      formalism resulting in 90 classes and 7 singletons. A thorough inspection of
      these yielded 7 interesting classes in terms of mini-SAR with IC(50) values
      ranging from 0.163 MUM to little over 25 MUM. The average ligand efficiency was
      found to be 0.3 for the best class. The classes thus discovered represent
      structurally novel chemotypes which can be taken up for further development.

PMID- 23117551
TI  - Attitudes supportive of sexual offending predict recidivism: a meta-analysis.
AB  - Attitudes supportive of sexual offending figure prominently in theories of sexual
      offending, as well as in contemporary assessment and treatment practices with sex
      offenders. Based on 46 samples (n = 13,782), this meta-analysis found that
      attitudes supportive of sexual offending had a small, yet reasonably consistent,
      relationship with sexual recidivism (Cohen's d = .22). To the extent that
      differences were observed, attitudes predicted recidivism better for child
      molesters than for rapists. There was no difference in the predictive accuracy of
      attitudes assessed at pretreatment or at posttreatment. The current study
      indicates that attitudes supportive of sexual offending is a psychologically
      meaningful risk factor for sex offenders. However, given that many different
      constructs have been designated as sex offender attitudes, further research and
      theory is needed to understand how these various constructs contribute to
      recidivism.

PMID- 23117552
TI  - Impact of basic research on advances in cardiology.

PMID- 23117550
TI  - Comparison of allogeneic vs autologous bone marrow-derived mesenchymal stem cells
      delivered by transendocardial injection in patients with ischemic cardiomyopathy:
      the POSEIDON randomized trial.
AB  - CONTEXT: Mesenchymal stem cells (MSCs) are under evaluation as a therapy for
      ischemic cardiomyopathy (ICM). Both autologous and allogeneic MSC therapies are
      possible; however, their safety and efficacy have not been compared. OBJECTIVE:
      To test whether allogeneic MSCs are as safe and effective as autologous MSCs in
      patients with left ventricular (LV) dysfunction due to ICM. DESIGN, SETTING, AND
      PATIENTS: A phase 1/2 randomized comparison (POSEIDON study) in a US tertiary
      care referral hospital of allogeneic and autologous MSCs in 30 patients with LV
      dysfunction due to ICM between April 2, 2010, and September 14, 2011, with 13
      month follow-up. INTERVENTION: Twenty million, 100 million, or 200 million cells
      (5 patients in each cell type per dose level) were delivered by transendocardial
      stem cell injection into 10 LV sites. MAIN OUTCOME MEASURES: Thirty-day
      postcatheterization incidence of predefined treatment-emergent serious adverse
      events (SAEs). Efficacy assessments included 6-minute walk test, exercise peak
      VO2, Minnesota Living with Heart Failure Questionnaire (MLHFQ), New York Heart
      Association class, LV volumes, ejection fraction (EF), early enhancement defect
      (EED; infarct size), and sphericity index. RESULTS: Within 30 days, 1 patient in
      each group (treatment-emergent SAE rate, 6.7%) was hospitalized for heart
      failure, less than the prespecified stopping event rate of 25%. The 1-year
      incidence of SAEs was 33.3% (n = 5) in the allogeneic group and 53.3% (n = 8) in
      the autologous group (P = .46). At 1 year, there were no ventricular arrhythmia
      SAEs observed among allogeneic recipients compared with 4 patients (26.7%) in the
      autologous group (P = .10). Relative to baseline, autologous but not allogeneic
      MSC therapy was associated with an improvement in the 6-minute walk test and the
      MLHFQ score, but neither improved exercise VO2 max. Allogeneic and autologous
      MSCs reduced mean EED by -33.21% (95% CI, -43.61% to -22.81%; P < .001) and
      sphericity index but did not increase EF. Allogeneic MSCs reduced LV end
      diastolic volumes. Low-dose concentration MSCs (20 million cells) produced
      greatest reductions in LV volumes and increased EF. Allogeneic MSCs did not
      stimulate significant donor-specific alloimmune reactions. CONCLUSIONS: In this
      early-stage study of patients with ICM, transendocardial injection of allogeneic
      and autologous MSCs without a placebo control were both associated with low rates
      of treatment-emergent SAEs, including immunologic reactions. In aggregate, MSC
      injection favorably affected patient functional capacity, quality of life, and
      ventricular remodeling. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT01087996.

PMID- 23117553
TI  - Inadequate request of transthoracic echocardiography according to the guidelines
      of the Brazilian Society of Cardiology.
AB  - BACKGROUND: Guidelines from medical societies suggest recommendations for the
      appropriate request of tests. In 2009, the Brazilian Society of Cardiology (BSC)
      published new guidelines for transthoracic echocardiography (TTE) request.
      OBJECTIVE: To evaluate the prevalence of Class III requests for TTE, as defined
      by the BSC Guidelines and analyze these requests profile comparing a public
      university hospital (PUH) with a private cardiology hospital (PCH). METHODS: We
      prospectively evaluated 779 consecutive outpatient TTE requests: 391 from the PCH
      and 388 from the PUH between December 2009 and May 2010. The indications studied
      were classified accordingly to the BSC guidelines. Request distribution was
      compared by Chi-square test. Statistical significance was set at p < 0.05.
      RESULTS: Of the 779 requests, 61 (7.8%) were considered Class III. Of these 14
      were from the public and 47 from the private hospital. The distribution of
      requests was statistically different between institutions (p < 0.001). Check-up
      in asymptomatic patients was the main inadequate indication, with 37 cases (33 in
      the private institution- 89.18%), followed by evaluation after angioplasty in 9
      cases (8 in the private institution - 88.88%); ventricular function monitoring in
      patients with stable heart failure in 6 cases (4 in the public institution -
      66.66%), post-bypass surgery in 5 cases (4 in the private institution- 80%), and
      evaluation of nonspecific electrocardiographic abnormalities in 4 cases (4 in the
      public institution - 100%). CONCLUSION: Asymptomatic patients' assessment was the
      main cause of inadequate TTE requests, which differs between institutions:
      routine check-up in the private and heart failure in the public hospital.

PMID- 23117556
TI  - Case 04/12: a 44-year-old male with rheumatic valvular heart disease with
      multiple previous surgeries of aortic valve replacement admitted for treatment of
      congestive heart failure.

PMID- 23117557
TI  - Prenatal management and outcome of junctional ectopic tachycardia and hydrops.

PMID- 23117558
TI  - Variant technique of extra-anatomic aortic bypass in aortic recoarctation.

PMID- 23117559
TI  - Incorporating social network effects into cost-effectiveness analysis: a
      methodological contribution with application to obesity prevention.
AB  - OBJECTIVES: To develop a methodology for integrating social networks into
      traditional cost-effectiveness analysis (CEA) studies. This will facilitate the
      economic evaluation of treatment policies in settings where health outcomes are
      subject to social influence. DESIGN: This is a simulation study based on a Markov
      model. The lifetime health histories of a cohort are simulated, and health
      outcomes compared, under alternative treatment policies. Transition probabilities
      depend on the health of others with whom there are shared social ties. SETTING:
      The methodology developed is shown to be applicable in any healthcare setting
      where social ties affect health outcomes. The example of obesity prevention is
      used for illustration under the assumption that weight changes are subject to
      social influence. MAIN OUTCOME MEASURES: Incremental cost-effectiveness ratio
      (ICER). RESULTS: When social influence increases, treatment policies become more
      cost effective (have lower ICERs). The policy of only treating individuals who
      span multiple networks can be more cost effective than the policy of treating
      everyone. This occurs when the network is more fragmented. CONCLUSIONS: (1) When
      network effects are accounted for, they result in very different values of
      incremental cost-effectiveness ratios (ICERs). (2) Treatment policies can be
      devised to take network structure into account. The integration makes it feasible
      to conduct a cost-benefit evaluation of such policies.

PMID- 23117560
TI  - Bicycling to school improves the cardiometabolic risk factor profile: a
      randomised controlled trial.
AB  - OBJECTIVES: To investigate whether bicycling to school improves cardiometabolic
      risk factor profile and cardiorespiratory fitness among children. DESIGN:
      Prospective, blinded, randomised controlled trial. SETTING: Single centre study
      in Odense, Denmark PARTICIPANTS: 43 children previously not bicycling to school
      were randomly allocated to control group (n=20) (ie, no change in lifestyle) or
      intervention group (ie, bicycling to school) (n=23). PRIMARY AND SECONDARY
      OUTCOME MEASURES: Change in cardiometabolic risk factor score and change in
      cardiorespiratory fitness. RESULTS: All participants measured at baseline
      returned at follow-up. Based upon intention-to-treat (ITT) analyses, clustering
      of cardiometabolic risk factors was lowered by 0.58 SD (95% CI -1.03 to -0.14,
      p=0.012) in the bicycling group compared to the control group. Cardiorespiratory
      fitness (l O(2)/min) per se did not increase significantly more in the
      intervention than in the control group (beta=0.0337, 95% CI -0.06 to 0.12,
      p=0.458). CONCLUSIONS: Bicycling to school counteracted a clustering of
      cardiometabolic risk factors and should thus be recognised as potential
      prevention of type 2 diabetes mellitus and cardiovascular disease (CVD). The
      intervention did, however, not elicit a larger increase in cardiorespiratory
      fitness in the intervention group as compared with the control group. TRIAL
      REGISTRATION: Registered at http://www.clinicaltrials.gov (NCT01236222).

PMID- 23117561
TI  - A population-based study of nearly 15 000 observations among Swedish women and
      men during 1973-2003.
AB  - OBJECTIVES: Global self-rated health (SRH) has become extensively used as an
      outcome measure in population health surveillance. The aim of this study was to
      analyse the effects of age and secular trend (year of investigation) on SRH.
      DESIGN: Prospective cohort study, using population-based data from eight ongoing
      cohort studies, with sampling performed between 1973 and 2003. SETTING: Sweden.
      PARTICIPANTS: 11 880 women and men, aged 25-99 years, providing 14 470
      observations. PRIMARY OUTCOME MEASURE: Global SRH. RESULTS: In multiple ordinal
      logistic regression analyses, adjusted for the effects of covariates, there were
      independent effects of age (p<0.0001) and of year of investigation (p<0.0001) on
      SRH. In women the association was linear, showing lower levels of SRH with
      increased age, and more recent year of investigation. In men the association was
      curvilinear, and thus more complex. The final model explained 76.2% of the SRH
      variance in women and 74.5% of the variance in men. CONCLUSIONS: SRH was strongly
      and inversely associated with age in both sexes, after adjustment for other
      outcome-affecting variables. There was a strongly significant effect of year of
      investigation indicating a change in SRH, in women towards lower levels over
      calendar time, in men with fluctuations across time.

PMID- 23117562
TI  - Cardiovascular risk factor management of myocardial infarction patients with and
      without diabetes in the Netherlands between 2002 and 2006: a cross-sectional
      analysis of baseline data.
AB  - OBJECTIVE: We examined levels and trends in cardiovascular risk factors and drug
      treatment in myocardial infarction (MI) patients with and without diabetes.
      DESIGN: Cross-sectional analysis of baseline Alpha Omega Trial data, a randomised
      controlled trial. SETTING: 32 hospitals in the Netherlands. PARTICIPANTS: In
      total, we had 1014 MI patients with diabetes (74% men) and 3823 without diabetes
      (79% men) aged 60-80 years, analysed over the period 2002-2006. RESULTS: Between
      2002 and 2006, a significantly decreasing trend in the prevalence of obesity (
      5%, p(trend)=0.02) and in systolic blood pressure (BP) levels (-5 mm Hg,
      p(trend)<0.0001) was demonstrated in non-diabetic patients, but not in diabetic
      patients. In 2006, obesity, mean systolic BP and serum triglyceride levels were
      significantly higher, whereas high-density lipoprotein cholesterol levels were
      lower in diabetic patients compared to those without. Prescription of
      antihypertensive drug (diabetic vs non-diabetic patients respectively, 95% vs
      93%, p=0.08) and statin treatment were high (86% and 90%, p=0.11). CONCLUSIONS: A
      high proportion of MI patients with and without diabetes was similarly treated
      with cardiovascular drugs. In spite of high drug treatment levels, more adverse
      risk factors were found in patients with diabetes.

PMID- 23117563
TI  - Using simple telehealth in primary care to reduce blood pressure: a service
      evaluation.
AB  - OBJECTIVES: This service evaluation examines how efficiently an innovative,
      simple and interactive blood pressure (BP) management intervention improves BP
      control in general practice. DESIGN: Prospective service evaluation. SETTING: Ten
      volunteer general practitioner (GP) practices in Stoke on Trent, UK.
      PARTICIPANTS: Practice staff identified 124 intervention patients and invited
      them to participate based on two inclusion criteria: (1) patient has chronic
      kidney disease (CKD) stages 3 or 4 with BP persistently >130/85 mm Hg or (2)
      patient is >50 years-old (without CKD stages 3-5) with BP persistently >140/90 mm
      Hg despite prescribed antihypertensive medication. Three selected hypertensive
      control patients per intervention patient underwent usual clinical care (n=364).
      INTERVENTIONS: Intervention patients used 'Florence', a simple, interactive
      mobile phone texting service with BP management intervention for 3 months, or for
      less time if their BP became controlled. Patients measured their BP, text their
      readings to Florence, received an immediate automatic response and had results
      reviewed by their GP/practice nurse at least weekly. MAIN OUTCOME MEASURES:
      Baseline data including recent BP readings and medications were collected;
      similar information was obtained for 6 months for both control and intervention
      patients. Average BP readings and medication usage were determined. RESULTS: At
      final data collection, five intervention patients had not yet completed the full
      programme. Control and intervention patients were well matched except that
      intervention patients had significantly greater baseline BP. Greatest BP
      reductions were among hypertensive intervention patients without CKD stages 3-5.
      Intervention patients had significantly more BP readings and more changes in
      medication over the 3-month data collection period. CONCLUSIONS: Simple
      telehealth is acceptable and effective in reducing patients' BP. In future,
      poorly controlled patients could be targeted to maximise BP reductions or broader
      use could improve diagnostic accuracy and accessibility for patients who struggle
      to regularly attend their GP surgery.

PMID- 23117564
TI  - Antenatal iron/folic acid supplements, but not postnatal care, prevents neonatal
      deaths in Indonesia: analysis of Indonesia Demographic and Health Surveys
      2002/2003-2007 (a retrospective cohort study).
AB  - OBJECTIVE: This study aimed to assess the contribution of postnatal services to
      the risk of neonatal mortality, and the relative contributions of antenatal
      iron/folic acid supplements and postnatal care in preventing neonatal mortality
      in Indonesia. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Data
      used in this study were the 2002-2007 Indonesia Demographic and Health Surveys,
      nationally representative surveys. The pooled data provided survival information
      of 26 591 most recent live-born infants within the 5-years prior to each
      interview. PRIMARY OUTCOMES: Primary outcomes were early neonatal mortality, that
      is, deaths in the first week, and all neonatal mortality, that is, deaths in the
      first month of life. Exposures were antenatal iron/folic acid supplementation and
      postnatal care from days 1 to 7. Potential confounders were community, socio
      economic status and birthing characteristics and perinatal healthcare. Cox
      regression was used to assess the association between study factors and neonatal
      mortality. RESULTS: Postnatal care services were not associated with newborn
      survival. Postnatal care on days 1-7 after birth did not reduce neonatal death
      (HR=1.00, 95% CI 0.55 to 1.83, p=1.00) and early postnatal care on day 1 was
      associated with an increased risk of early neonatal death (HR=1.27, 95% CI 0.69
      to 2.32, p=0.44) possibly reflecting referral of ill newborns. Early postnatal
      care on day 1 was not protective for neonatal deaths on days 2-7 whether provided
      by doctors (HR 3.61, 95% CI 1.54 to 8.45, p<0.01), or by midwives or nurses (HR
      1.38, 95% CI 0.53 to 3.57, p=0.512). In mothers who took iron/folic acid
      supplements during pregnancy, the risk of early neonatal death was reduced by 51%
      (HR=0.49, 95% CI 0.30 to 0.79, p<0.01). CONCLUSIONS: We found no protective
      effect of postnatal care against neonatal deaths in Indonesia. However, important
      reductions in the risk of neonatal death were found for women who reported use of
      antenatal iron/folic acid supplements during pregnancy.

PMID- 23117565
TI  - Gene expression profiles of alveolar type II cells of chronic obstructive
      pulmonary disease: a case-control study.
AB  - OBJECTIVES: The aim of this study was to identify the gene expression pattern
      specific in alveolar epithelial type II cells (ATII cells) isolated from patients
      with chronic obstructive pulmonary disease (COPD). DESIGN: Case control. SETTING:
      Two hospitals in Japan. PARTICIPANTS: Three patients without COPD and three
      patients with COPD in microarray analyses. Five smokers without COPD and nine
      smokers with COPD in the following analyses.   PRIMARY AND SECONDARY OUTCOME
      MEASURED:  Primary outcome included identification of differentially expressed
      genes and activated or inhibited pathways in ATII cells of the patients with
      COPD, compared to those of the patients without COPD, using Affymetrix gene
      expression arrays. Secondary outcome included validation of the results of
      microarray analyses by quantitative reverse transcription-PCR. RESULTS: We
      isolated ATII cells from COPD and non-COPD lungs using fluorescence-activated
      cell sorting. We performed Affymetrix gene expression arrays on both types of
      ATII cells. Gene set enrichment analyses revealed that two major gene sets were
      enriched in ATII cells from COPD lungs: interferon-responsive gene sets and gene
      sets associated with cell cycle progression. Gene ontology term enrichment
      analyses indicated that among the interferon-stimulated genes, ATII cells in COPD
      expressed genes such as PSMB8, PSMB9, TAP1 and TAP2 associated with the antigen
      processing and presentation pathway. We validated the results of the microarray
      analyses using quantitative reverse transcriptase-PCR. In addition, FACS analysis
      indicated that the percentage of ATII cells to CD45-negative lung cells isolated
      from COPD lungs were significantly increased more than that from non-COPD lungs.
      CONCLUSIONS: Our study demonstrated that interferon-stimulated genes involved in
      the antigen processing and presentation pathway and genes involved in cell cycle
      progression were enriched in ATII cells of the patients with COPD. These pathways
      might alter phenotypes of ATII cells in COPD lungs.

PMID- 23117566
TI  - Access to facility delivery and caesarean section in north-central Liberia: a
      cross-sectional community-based study.
AB  - OBJECTIVE: Rural north-central Liberia has one of the world's highest maternal
      mortality ratios. We studied health facility birthing service utilisation and the
      motives of women seeking or not seeking facility-based care in north-central
      Liberia. DESIGN: Cross-sectional community-based structured interviews and health
      facility medical record review. SETTING: A regional hospital and the surrounding
      communities in rural north-central Liberia. PARTICIPANTS: A convenience sample of
      307 women between 15 and 49 years participated in structured interviews. 1031
      deliveries performed in the regional hospital were included in the record review.
      PRIMARY OUTCOMES: Delivery within a health facility and caesarean delivery rates
      were used as indicators of direct utilisation of care and as markers of
      availability of maternal health services. RESULTS: Of 280 interview respondents
      with a prior childbirth, only 47 (16.8%) delivered their last child in a health
      facility. Women who did not use formal services cited cost, sudden labour and
      family tradition or religion as their principal reasons for home delivery. At the
      regional hospital, the caesarean delivery rate was 35.5%. CONCLUSIONS: There is
      an enormous unmet need for maternal health services in north-central Liberia.
      Greater outreach and referral services as well as community-based education among
      women, family members and traditional midwives are vital to improve the timely
      utilisation of care.

PMID- 23117567
TI  - A pragmatic method for electronic medical record-based observational studies:
      developing an electronic medical records retrieval system for clinical research.
AB  - OBJECTIVE: The use of electronic medical record (EMR) data is necessary to
      improve clinical research efficiency. However, it is not easy to identify
      patients who meet research eligibility criteria and collect the necessary
      information from EMRs because the data collection process must integrate various
      techniques, including the development of a data warehouse and translation of
      eligibility criteria into computable criteria. This research aimed to demonstrate
      an electronic medical records retrieval system (ERS) and an example of a hospital
      based cohort study that identified both patients and exposure with an ERS. We
      also evaluated the feasibility and usefulness of the method. DESIGN: The system
      was developed and evaluated. PARTICIPANTS: In total, 800 000 cases of clinical
      information stored in EMRs at our hospital were used. PRIMARY AND SECONDARY
      OUTCOME MEASURES: The feasibility and usefulness of the ERS, the method to
      convert text from eligible criteria to computable criteria, and a confirmation
      method to increase research data accuracy. RESULTS: To comprehensively and
      efficiently collect information from patients participating in clinical research,
      we developed an ERS. To create the ERS database, we designed a multidimensional
      data model optimised for patient identification. We also devised practical
      methods to translate narrative eligibility criteria into computable parameters.
      We applied the system to an actual hospital-based cohort study performed at our
      hospital and converted the test results into computable criteria. Based on this
      information, we identified eligible patients and extracted data necessary for
      confirmation by our investigators and for statistical analyses with our ERS.
      CONCLUSIONS: We propose a pragmatic methodology to identify patients from EMRs
      who meet clinical research eligibility criteria. Our ERS allowed for the
      efficient collection of information on the eligibility of a given patient,
      reduced the labour required from the investigators and improved the reliability
      of the results.

PMID- 23117568
TI  - Discharge disposition disagreements and re-admission risk among older adults: a
      retrospective cohort study.
AB  - OBJECTIVES: Re-admissions after hospitalisation are a burden for patients and
      costly. Our objective was to examine whether re-admissions were increased among
      older patients when they or their surrogates disagreed with the discharge
      disposition recommended by the clinical team at hospital discharge. DESIGN:
      Retrospective cohort study. SETTING: Large academic medical centre in New York,
      NY. PARTICIPANTS: 514 hospital discharges of older patients admitted to a
      geriatric inpatient service between 1 July 2007 and 30 June 2008.   PRIMARY
      OUTCOME MEASURE AND MAIN INDEPENDENT VARIABLE:  Re-admissions for any reason to
      any hospital within 30 days after discharge were identified. Agreement or
      disagreement with the discharge disposition recommended by the clinical team at
      hospital discharge was assessed. RESULTS: Among 514 hospital discharges of older
      patients, the mean age was 83.1 years (SD=8.3), 75.7% were women, and
      approximately 90% were living at home prior to hospitalisation, despite 47.1%
      having some degree of cognitive impairment and 56.4% requiring assistance for
      activities of daily living or independent activities of daily living. There were
      42 (8.2%) disposition disagreements; the majority (n=25; 59.5%) were discharged
      home despite the clinical team's recommendation for discharge to an acute or
      subacute facility. Overall, 158 (30.7%) were re-admitted within 30 days. There
      was no difference in re-admission rates between discharges with and without
      disposition disagreements (33.3% (144 of 472) vs 30.5% (14 of 42), respectively;
      OR=1.14, 95% CI 0.57 to 2.19; p=0.71). Adjusted analyses were consistent with
      these findings. CONCLUSIONS: Discharge disposition disagreements occurred
      relatively infrequently after hospitalisation among a group of older patients
      managed by a geriatrics inpatient service. In addition, we found no differences
      in re-admission when comparing patients who agreed or disagreed with the clinical
      team's recommended discharge disposition.

PMID- 23117569
TI  - Self-reported treatment, workplace-oriented rehabilitation, change of occupation
      and subsequent sickness absence and disability pension among employees long-term
      sick-listed for psychiatric disorders: a prospective cohort study.
AB  - AIM: To examine whether self-reported treatments, workplace-oriented
      rehabilitation and change of occupation were associated with subsequent sickness
      absence and disability pension among long-term sick-listed for psychiatric
      disorders. DESIGN: A prospective cohort study. SETTING AND PARTICIPANTS: 5200
      employees (80% from the Swedish municipalities and county councils and 20% manual
      workers from the Swedish industry) were randomly selected who in 1999 in the
      register of AFA Insurance had a new spell of long-term sickness absence due to a
      psychiatric disorder. Of these, 99 were excluded (duplicates and deaths, persons
      living abroad, with protected personal information), and 5101 received a
      questionnaire in 2001. 3053 individuals responded (60%). After the exclusion of
      employees with no sick leave in 1999 according to the Swedish social insurance
      agency, aged 62 years and older, with disability pension 1999-2001, no self
      reported treatment, and with missing information on the covariates, our final
      study group was 2324 individuals. Logistic regression analyses were performed.
      OUTCOME MEASURES: Sickness absence (>90 days) and disability pension (>0 day).
      RESULTS: 45% had sickness absence and 18% a new disability pension in 2002. Drug
      treatment and physiotherapy, respectively, were associated with increased odds of
      sickness absence (OR 1.56, 95% CI 1.28 to 1.90; OR 1.43, 95% CI 1.21 to 1.69),
      and disability pension (OR 1.79, 95% CI 1.34 to 2.41; OR 1.75, 95% CI 1.40 to
      2.18). Workplace-oriented rehabilitation and change of occupation, respectively,
      reduced the odds of sickness absence (OR 0.70, 95% CI 0.59 to 0.83; OR 0.35, 95%
      CI 0.27 to 0.45). CONCLUSIONS: We found a pattern of poorer outcome of drug
      treatment and physiotherapy compared with other treatments (psychotherapy,
      workplace-oriented rehabilitation and complementary or alternative medicine) in
      terms of increased odds of sickness absence and disability pension. Workplace
      oriented rehabilitation and/or change of occupation were associated with reduced
      odds of sick leave. Studies with a randomised controlled trial design are needed
      to examine the effect on sick leave of a workplace-oriented intervention.

PMID- 23117570
TI  - Can manual ability be measured with a generic ABILHAND scale? A cross-sectional
      study conducted on six diagnostic groups.
AB  - OBJECTIVES: Several ABILHAND Rasch-built manual ability scales were previously
      developed for chronic stroke (CS), cerebral palsy (CP), rheumatoid arthritis
      (RA), systemic sclerosis (SSc) and neuromuscular disorders (NMD). The present
      study aimed to explore the applicability of a generic manual ability scale
      unbiased by diagnosis and to study the nature of manual ability across diagnoses.
      DESIGN: Cross-sectional study. SETTING: Outpatient clinic homes (CS, CP, RA),
      specialised centres (CP), reference centres (CP, NMD) and university hospitals
      (SSc). PARTICIPANTS: 762 patients from six diagnostic groups: 103 CS adults, 113
      CP children, 112 RA adults, 156 SSc adults, 124 NMD children and 124 NMD adults.
      PRIMARY AND SECONDARY OUTCOME MEASURES: Manual ability as measured by the
      ABILHAND disease-specific questionnaires, diagnosis and nature (ie, uni-manual or
      bi-manual involvement and proximal or distal joints involvement) of the ABILHAND
      manual activities. RESULTS: The difficulties of most manual activities were
      diagnosis dependent. A principal component analysis highlighted that 57% of the
      variance in the item difficulty between diagnoses was explained by the symmetric
      or asymmetric nature of the disorders. A generic scale was constructed, from a
      metric point of view, with 11 items sharing a common difficulty among diagnoses
      and 41 items displaying a category-specific location (asymmetric: CS, CP; and
      symmetric: RA, SSc, NMD). This generic scale showed that CP and NMD children had
      significantly less manual ability than RA patients, who had significantly less
      manual ability than CS, SSc and NMD adults. However, the generic scale was less
      discriminative and responsive to small deficits than disease-specific
      instruments. CONCLUSIONS: Our finding that most of the manual item difficulties
      were disease-dependent emphasises the danger of using generic scales without
      prior investigation of item invariance across diagnostic groups. Nevertheless, a
      generic manual ability scale could be developed by adjusting and accounting for
      activities perceived differently in various disorders.

PMID- 23117572
TI  - Sodium/iodide symporter is expressed in the majority of seminomas and embryonal
      testicular carcinomas.
AB  - Testicular cancer is the most frequent cancer in young men. The large majority of
      patients have a good prognosis, but in a small group of tumors, the current
      treatments are not effective. Radioiodine is routinely used in the treatment of
      thyroid cancer and is currently investigated as a potential therapeutic tool even
      for extra-thyroid tumors able to concentrate this radioisotope. Expression of
      Na(+)/I(-) symporter (NIS (SLC5A5)), the glycoprotein responsible for iodide
      transport, has been demonstrated in normal testicular tissue. In this study, we
      analyzed NIS expression in a large series of testicular carcinomas. Our
      retrospective series included 107 patients operated for testicular tumors: 98
      typical seminomas, six embryonal carcinomas, one mixed embryonal choriocarcinoma,
      and two Leydig cells tumors. Expression and regulation of NIS mRNA and protein
      levels were also investigated in human embryonal testicular carcinoma cells
      (NTERA) by real-time RT-PCR and western blotting respectively.
      Immunohistochemical analysis showed the presence of NIS in the large majority of
      seminomas (90/98) and embryonal carcinomas (5/7) of the testis but not in Leydig
      cell carcinomas. Expression of NIS protein was significantly associated with
      lymphovascular invasion. In NTERA cells treated with the histone deacetylase
      inhibitors SAHA and valproic acid, a significant increase in NIS mRNA (about 60-
      and 30-fold vs control, P<0.001 and P<0.01 respectively) and protein levels,
      resulting in enhanced ability to uptake radioiodine, was observed. Finally, NIS
      expression in testicular tumors with the more aggressive behavior is of interest
      for the potential use of targeting NIS to deliver radioiodine in malignant cells.

PMID- 23117571
TI  - Observational Research in Childhood Infectious Diseases (ORChID): a dynamic birth
      cohort study.
AB  - INTRODUCTION: Even in developed economies infectious diseases remain the most
      common cause of illness in early childhood. Our current understanding of the
      epidemiology of these infections is limited by reliance on data from decades ago
      performed using low-sensitivity laboratory methods, and recent studies reporting
      severe, hospital-managed disease. METHODS AND ANALYSIS: The Observational
      Research in Childhood Infectious Diseases (ORChID) study is an ongoing study
      enrolling a dynamic birth cohort to document the community-based epidemiology of
      viral respiratory and gastrointestinal infections in early childhood. Women are
      recruited antenatally, and their healthy newborn is followed for the first 2
      years of life. Parents keep a daily symptom diary for the study child, collect a
      weekly anterior nose swab and dirty nappy swab and complete a burden diary when a
      child meets pre-defined illness criteria. Specimens will be tested for a wide
      range of viruses by real-time PCR assays. Primary analyses involves calculating
      incidence rates for acute respiratory illness (ARI) and acute gastroenteritis
      (AGE) for the cohort by age and seasonality. Control material from children when
      they are without symptoms will allow us to determine what proportion of ARIs and
      AGE can be attributed to specific pathogens. Secondary analyses will assess the
      incidence and shedding duration of specific respiratory and gastrointestinal
      pathogens. ETHICS AND DISSEMINATION: This study is approved by The Human Research
      Ethics Committees of the Children's Health Queensland Hospital and Health
      Service, the Royal Brisbane and Women's Hospital and The University of
      Queensland. TRIAL REGISTRATION: clinicaltrials.gov NCT01304914.

PMID- 23117573
TI  - Familial influences on conduct disorder reflect 2 genetic factors and 1 shared
      environmental factor.
AB  - CONTEXT: Prior studies suggest that antisocial behavior in childhood and
      adolescence reflects multiple symptomatic dimensions. However, to our knowledge,
      no prior study has evaluated the underlying nature of the etiologic influences
      contributing to conduct disorder (CD) symptoms as defined in the DSM. OBJECTIVE:
      To determine the structure of genetic and environmental risk factors for CD.
      DESIGN: Population-based twin registry. SETTING: Virginia. PARTICIPANTS: Two
      thousand seven hundred sixty-nine members of male-male twin pairs from the
      Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. MAIN
      OUTCOME MEASURE: Retrospective self-reported symptoms of CD. RESULTS: The best
      fitting multivariate twin model included 2 genetic factors, 1 shared
      environmental common factor, and 1 nonshared environmental common factor, along
      with criterion-specific genetic and nonshared environmental effects. The CD
      criteria with the strongest loadings on the 2 genetic factors were, respectively,
      those reflecting rule breaking (eg, playing hooky) and overt aggressive acts (eg,
      hurting people). The shared environmental common factor had salient loadings on a
      distinct set of criteria reflecting covert delinquent acts (eg, stealing and
      hurting animals). Loadings on the single nonshared environmental common factor
      were more uniform and less selective. Scores on the 3 familial CD factors were
      differentially associated with a range of personality, psychopathology, and
      demographic factors. CONCLUSIONS: From a genetic perspective, the DSM criteria
      for CD do not reflect a single dimension of liability. The familial risk to CD is
      composed of 2 discrete dimensions of genetic risk, reflecting rule breaking and
      overt aggression, and 1 dimension of shared environmental risk, reflecting covert
      delinquency. These 3 familial factors differ meaningfully in their association
      with a range of relevant validators.

PMID- 23117574
TI  - HIV test avoidance among people who inject drugs in Thailand.
AB  - Case identification is a key component of HIV prevention efforts; yet rates of
      HIV testing remain low in some settings. We explored factors associated with HIV
      test avoidance among people who inject drugs (IDU) in Thailand. Between July and
      October 2011, 350 Thai IDU participated in the study. In bivariate analyses, male
      gender, high intensity drug use, syringe sharing, increased police presence, and
      being refused healthcare services were positively associated with HIV test
      avoidance, while ever receiving a hepatitis C test was negatively associated. Our
      findings highlight the need for interventions to reduce stigma in this setting. 

PMID- 23117575
TI  - There is always hope after PCI and stenting.
AB  - Nowadays the introduction of intracoronary stents into clinical practice has
      totally changed the approach to the treatment of diffuse and obstructive coronary
      artery disease. Although optimal antiaggregant therapy has ensured a low
      incidence of subacute stent thrombosis, recurrent restenosis remains the major
      limitation of these intracoronary devices. In such circumstances, surgery may
      represent the only choice for definitive treatment of recurrent ischemic heart
      disease. We report an uncommon and challenging way to achieve a complete off-pump
      coronary revascularization of a seriously diseased, 'full metal jacket' left
      anterior descending artery (LAD), combining three different techniques at the
      same time: stent removal, endarterectomy and coronary artery bypass graft (CABG).

PMID- 23117576
TI  - Flow focusing geometry generates droplets through a plug and squeeze mechanism.
AB  - Microdroplets are typically generated by one of two microfluidic geometries, the
      T-junction and flow focusing. These two geometries are often thought to form
      drops through different mechanisms. Here, by directly measuring the pressures in
      the drop maker, we show that flow focus devices exhibit pressure fluctuations
      that are essentially identical to those found in T-junctions, suggesting that, in
      these devices and low-to-moderate capillary number, the drop formation process is
      also dominated by interfacial stresses and proceeds through a plugging-squeezing
      process.

PMID- 23117577
TI  - Combination therapy with VEGFR2 and EGFR siRNA enhances the antitumor effect of
      cisplatin in non-small cell lung cancer xenografts.
AB  - RNA targeting the murine vascular endothelial growth factor receptor 2 (VEGFR2)
      gene was designed and validated for efficient and robust silencing in vitro and
      was delivered by polyethylenimines (PEI) in vivo to investigate the antitumor
      effect on non-small cell lung cancer (NSCLC) xenografts. The following dosage
      regimens were tested for their tumor inhibitory effect in vivo: VEGFR2 siRNA,
      epidermal growth factor receptor (EGFR) siRNA, VEGFR2 siRNA+EGFR siRNA, cisplatin
      alone and VEGFR2 siRNA+ EGFR siRNA+cisplatin. Targeted silencing of both VEGFR2
      and EGFR expression by siRNA, combined with low-dose cisplatin, was found to
      effectively inhibit tumor growth and extend the survival time of mice bearing the
      NSCLC xenografts. These results suggest that combination therapy using siRNAs and
      chemotherapy agents might offer a novel strategy for cancer treatment in the
      future.

PMID- 23117578
TI  - The p38 MAPK PMK-1 shows heat-induced nuclear translocation, supports chaperone
      expression, and affects the heat tolerance of Caenorhabditis elegans.
AB  - The p38 mitogen-activated protein kinase PMK-1 of Caenorhabditis elegans has been
      associated with heavy metal, oxidative and pathogen stress. Pmk-1 is part of an
      operon comprising three p38 homologues, with pmk-1 expression suggested to be
      regulated by the operon promoter. There are contradictory reports about the
      cellular localization of PMK-1. We were interested to study principles of pmk-1
      expression and to analyze the role of PMK-1 under heat stress. Using a
      translational GFP reporter, we found pmk-1 expression to be driven by a promoter
      in front of pmk-1. PMK-1 was detected in intestinal cells and neurons, with a
      cytoplasmic localization at moderate temperature. Increasing temperature above 32
      degrees C, however, induced a nuclear translocation of PMK-1 as well as PMK-1
      accumulation near to apical membranes. Testing survival rates revealed 34-35 
      degrees C as critical temperature range, where short-term survival severely
      decreased. Mutants of the PMK-1 pathway (pmk-1Delta, sek-1Delta, mek-1Delta) as
      well as a mutant of JNK pathway (jnk-1Delta) showed significantly lower survival
      rates than wild-type or mutants of other pathways (kgb-1Delta, daf-2Delta).
      Rescue and overexpression experiments verified the negative effects of pmk-1Delta
      on heat tolerance. Studying gene expression by RNA-seq and semi-quantitative
      reverse transcriptase polymerase chain reaction revealed positive effects of the
      PMK-1 pathway on the expression of genes for chaperones, protein biosynthesis,
      protein degradation, and other functional categories. Thus, the PMK-1 pathway is
      involved in the heat stress responses of C. elegans, possibly by a PMK-1-mediated
      activation of the transcription factor SKN-1 and/or an indirect or direct PMK-1
      dependent activation (hyperphosphorylation) of heat-shock factor 1.

PMID- 23117579
TI  - Synthesis and pharmacological activity of alkaloids from embryo of lotus, Nelumbo
      nucifera.
AB  - Bisbenzylisoquinoline alkaloid, nelumboferine which was recently isolated from
      the embryo of Nelumbo nucifera, and stereoisomers of neferine, which is a major
      alkaloid of the embryo of N. nucifera, were stereoselectively synthesized.
      Pharmacological activity of nelumboferine, stereoisomers of neferine, liensinine,
      isoliensinine, and O-methylneferine were evaluated.

PMID- 23117580
TI  - Modifying metabolically sensitive histone marks by inhibiting glutamine
      metabolism affects gene expression and alters cancer cell phenotype.
AB  - The interplay of metabolism and epigenetic regulatory mechanisms has become a
      focal point for a better understanding of cancer development and progression. In
      this study, we have acquired data supporting previous observations that
      demonstrate glutamine metabolism affects histone modifications in human breast
      cancer cell lines. Treatment of non-invasive epithelial (T-47D and MDA-MB-361)
      and invasive mesenchymal (MDA-MB-231 and Hs-578T) breast cancer cell lines with
      the glutaminase inhibitor, Compound 968, resulted in cytotoxicity in all cell
      lines, with the greatest effect being observed in MDA-MB-231 breast cancer cells.
      Compound 968-treatment induced significant downregulation of 20 critical cancer
      related genes, the majority of which are anti-apoptotic and/or promote
      metastasis, including AKT, BCL2, BCL2L1, CCND1, CDKN3, ERBB2, ETS1, E2F1, JUN,
      KITLG, MYB, and MYC. Histone H3K4me3, a mark of transcriptional activation, was
      reduced at the promoters of all but one of these critical cancer genes. The
      decrease in histone H3K4me3 at global and gene-specific levels correlated with
      reduced expression of SETD1 and ASH2L, genes encoding the histone H3K4
      methyltransferase complex. Further, the expression of other epigenetic regulatory
      genes, known to be downregulated during apoptosis (e.g., DNMT1, DNMT3B, SETD1 and
      SIRT1), was also downregulated by Compound 968. These changes in gene expression
      and histone modifications were accompanied by the activation of apoptosis, and
      decreased invasiveness and resistance of MDA-MB-231 cells to chemotherapeutic
      drug doxorubicin. The results of this study provide evidence to a link between
      cytotoxicity caused by inhibiting glutamine metabolism with alterations of the
      epigenome of breast cancer cells and suggest that modification of intracellular
      metabolism may enhance the efficiency of epigenetic therapy.

PMID- 23117581
TI  - Hyperlipidemia, oxidative stress, and intima media thickness in children with
      chronic kidney disease.
AB  - BACKGROUND: The roles of dyslipidemia and oxidative stress in the early phases of
      atherosclerosis were tested in children with chronic kidney disease (CKD). Intima
      media thickness of common carotid arteries (cIMT) is used as a measure of early
      atherosclerosis. METHODS: Fifty-two pediatric CKD patients were enrolled in the
      study (10 with chronic renal failure [CRF], 22 with a renal transplant [RT], 20
      with chronic hemodialysis (cHD) patients, and 36 healthy children (control group,
      CG). Lipid status, oxidative stress, and paraoxonase 1 (PON1) status were
      assessed. cIMT was measured by ultrasound, adjusted for age and sex, and
      presented as standard deviation scores (SDS). RESULTS: Children with CKD had
      disturbed lipid content, which was most pronounced in cHD children, with higher
      free cholesterol and triglycerides compared with healthy children. Oxidative
      stress was markedly increased (malodialdehyde [MDA, MUmol/L]: CRF 1.50 +/- 0.26,
      RT 1.55 +/- 0.40, cHD 1.77 +/- 0.34, CG 0.97 +/- 0.33, p < 0.001) and
      antioxidative defense was compromised (superoxide dismutase [SOD, U/L]: CG 120 +/
      21, CRF 84 +/- 25, RT 93 +/- 12, cHD 119 +/- 37, p < 0.001). Multiple linear
      regression analysis showed that a model that included disease duration, blood
      pressure, urea, lipid, and oxidative status parameters accounted for more than
      90% of the variability of cIMT-SDS. CONCLUSIONS: Early atherosclerosis in CKD
      children is caused, at least in part, by dyslipidemia and oxidative stress.
      Monitoring of vessel wall changes, along with assessment of oxidative stress
      status and high density lipoprotein (HDL) functionality is necessary to ensure
      better therapeutic strategies for delaying atherosclerotic changes in their
      asymptomatic phase.

PMID- 23117582
TI  - Beyond mineral metabolism, is there an interplay between FGF23 and vitamin D in
      innate immunity?
AB  - Fibroblast growth factor 23 (FGF23) is an "endocrine" FGF acting in the kidney as
      a phosphaturic hormone and a suppressor of active vitamin D, through an
      inhibition of the 1alpha hydroxylase and a stimulation of the 24 hydroxylase.
      Beyond its well-known effects on the bone/kidney/parathyroid axis and its
      deregulation during chronic kidney disease (CKD), recent evidence has revealed
      its direct systemic effects on cardiovascular health. In the meantime, studies
      have highlighted the health implications for vitamin D inside and outside CKD
      that also extend beyond its classical actions on mineral homeostasis and bone
      metabolism: vitamin D has indeed been shown to exert pluripotent non-classical
      effects as a modulator of immune function in monocytes, mainly through the
      stimulation of the antimicrobial cathelicidin. The aim of this review is to
      provide new insights on the interplay between FGF23 and vitamin D in innate
      immunity in the context of CKD.

PMID- 23117583
TI  - Bioluminescence imaging of NADPH oxidase activity in different animal models.
AB  - NADPH oxidase is a critical enzyme that mediates antibacterial and antifungal
      host defense. In addition to its role in antimicrobial host defense, NADPH
      oxidase has critical signaling functions that modulate the inflammatory response
      (1). Thus, the development of a method to measure in "real-time" the kinetics of
      NADPH oxidase-derived ROS generation is expected to be a valuable research tool
      to understand mechanisms relevant to host defense, inflammation, and injury.
      Chronic granulomatous disease (CGD) is an inherited disorder of the NADPH oxidase
      characterized by severe infections and excessive inflammation. Activation of the
      phagocyte NADPH oxidase requires translocation of its cytosolic subunits
      (p47(phox), p67(phox), and p40(phox)) and Rac to a membrane-bound flavocytochrome
      (composed of a gp91(phox) and p22(phox) heterodimer). Loss of function mutations
      in any of these NADPH oxidase components result in CGD. Similar to patients with
      CGD, gp91(phox) -deficient mice and p47(phox)-deficient mice have defective
      phagocyte NADPH oxidase activity and impaired host defense (2, 13). In addition
      to phagocytes, which contain the NADPH oxidase components described above, a
      variety of other cell types express different isoforms of NADPH oxidase. Here, we
      describe a method to quantify ROS production in living mice and to delineate the
      contribution of NADPH oxidase to ROS generation in models of inflammation and
      injury. This method is based on ROS reacting with L-012 (an analogue of luminol)
      to emit luminescence that is recorded by a charge-coupled device (CCD). In the
      original description of the L-012 probe, L-012-dependent chemiluminescence was
      completely abolished by superoxide dismutase, indicating that the main ROS
      detected in this reaction was superoxide anion (14). Subsequent studies have
      shown that L-012 can detect other free radicals, including reactive nitrogen
      species (15, 16). Kielland et al. (16) showed that topical application of phorbol
      myristate acetate, a potent activator of NADPH oxidase, led to NADPH oxidase
      dependent ROS generation that could be detected in mice using the luminescent
      probe L-012. In this model, they showed that L-012-dependent luminescence was
      abolished in p47(phox)-deficient mice. We compared ROS generation in wildtype
      mice and NADPH oxidase-deficient p47(phox-/-) mice (2) in the following three
      models: 1) intratracheal administration of zymosan, a pro-inflammatory fungal
      cell wall-derived product that can activate NADPH oxidase; 2) cecal ligation and
      puncture (CLP), a model of intra-abdominal sepsis with secondary acute lung
      inflammation and injury; and 3) oral carbon tetrachloride (CCl4), a model of ROS
      dependent hepatic injury. These models were specifically selected to evaluate
      NADPH oxidase-dependent ROS generation in the context of non-infectious
      inflammation, polymicrobial sepsis, and toxin-induced organ injury, respectively.
      Comparing bioluminescence in wildtype mice to p47(phox-/-) mice enables us to
      delineate the specific contribution of ROS generated by p47(phox)-containing
      NADPH oxidase to the bioluminescent signal in these models. Bioluminescence
      imaging results that demonstrated increased ROS levels in wildtype mice compared
      to p47(phox-/-) mice indicated that NADPH oxidase is the major source of ROS
      generation in response to inflammatory stimuli. This method provides a minimally
      invasive approach for "real-time" monitoring of ROS generation during
      inflammation in vivo.

PMID- 23117584
TI  - Mixed results for bone marrow-derived cell therapy for ischemic heart disease.

PMID- 23117585
TI  - StemCellDB: the human pluripotent stem cell database at the National Institutes
      of Health.
AB  - Much of the excitement generated by induced pluripotent stem cell technology is
      concerned with the possibility of disease modeling as well as the potential for
      personalized cell therapy. However, to pursue this it is important to understand
      the 'normal' pluripotent state including its inherent variability. We have
      performed various molecular profiling assays for 21 hESC lines and 8 hiPSC lines
      to generate a comprehensive snapshot of the undifferentiated state of pluripotent
      stem cells. Analysis of the gene expression data revealed no iPSC-specific gene
      expression pattern in accordance with previous reports. We further compared
      cells, differentiated as embryoid bodies in 2 media proposed to initiate
      differentiation towards separate cell fates, as well as 20 adult tissues. From
      this analysis we have generated a gene list which defines pluripotency and
      establishes a baseline for the pluripotent state. Finally, we provide lists of
      genes enriched under both differentiation conditions which show the proposed bias
      toward independent cell fates.

PMID- 23117586
TI  - Respiratory change in ECG-wave amplitude is a reliable parameter to estimate
      intravascular volume status.
AB  - Electrocardiogram (ECG) is a standard type of monitoring in intensive care
      medicine. Several studies suggest that changes in ECG morphology may reflect
      changes in volume status. The "Brody effect", a theoretical analysis of left
      ventricular (LV) chamber size influence on QRS-wave amplitude, is the key element
      of this phenomenon. It is characterised by an increase in QRS-wave amplitude that
      is induced by an increase in ventricular preload. This study investigated the
      influence of changes in intravascular volume status on respiratory variations of
      QRS-wave amplitudes (DeltaECG) compared with respiratory pulse pressure
      variations (DeltaPP), considered as a reference standard. In 17 pigs, ECG and
      arterial pressure were recorded. QRS-wave amplitude was measured from the Biopac
      recording to ensure that in all animals ECG electrodes were always at the same
      location. Maximal QRS amplitude (ECGmax) and minimal QRS amplitude (ECGmin) were
      determined over one respiratory cycle. DeltaECG was calculated as 100 * [(ECGmax 
      ECGmin)/(ECGmax + ECGmin)/2]. DeltaECG and DeltaPP were simultaneously recorded.
      Measurements were performed at different time points: during normovolemic
      conditions, after haemorrhage (25 mL/kg), and following re-transfusion (25 mL/kg)
      with constant tidal volume (10 mL/kg) and respiration rate (15 breath/min). At
      baseline, DeltaPP and DeltaECG were both <12 %. DeltaPP were significantly
      correlated with DeltaECG (r(2) = 0.89, p < 0.001). Volume loss induced by
      haemorrhage increased significantly DeltaPP and DeltaECG. Moreover, during this
      state, DeltaPP were significantly correlated with DeltaECG (r(2) = 0.86, p <
      0.001). Re-transfusion significantly decreased DeltaPP and DeltaECG, and DeltaPP
      were significantly correlated with DeltaECG (r(2) = 0.90, p < 0.001). The
      observed correlations between DeltaPP and DeltaECG at each time point of the
      study suggest that DeltaECG is a reliable parameter to estimate the changes in
      intravascular volume status and provide experimental confirmation of the "Brody
      effect."

PMID- 23117588
TI  - UC Davis transgenic animal research conference VIII.

PMID- 23117587
TI  - Generation and characterization of Tbx1-AmCyan1 transgenic reporter mouse line
      that selectively labels developing thymus primordium.
AB  - Thymus development is a complicated process that includes highly dynamic
      morphological changes and reciprocal tissue interactions between endoderm-derived
      epithelial cells of the anterior foregut and neural crest-derived mesenchymal
      cells. We generated and characterized a Tbx1-AmCyan1 reporter transgenic mouse to
      visualize thymus precursor cells during early embryonic development. In
      transgenic embryos, AmCyan1 fluorescence was specifically detected in the
      endoderm of the developing 3rd and 4th pharyngeal pouches and later in thymus
      epithelium until E14.5. Cells expressing AmCyan1 that were isolated based on
      AmCyan1 fluorescence expressed endodermal, thymic, and parathyroid markers, but
      they did not express neural crest or endothelial markers; these findings
      indicated that this transgenic mouse strain could be used to collect thymic or
      parathyroid precursor cells or both. We also showed that in nude mice, which
      exhibit defects in thymus development, the thymus precursors were clearly labeled
      with AmCyan1. In summary, these AmCyan1-fluorescent transgenic mice are useful
      for investigating early thymus development.

PMID- 23117590
TI  - Interrogating discourse: the application of Foucault's methodological discussion
      to specific inquiry.
AB  - Discourse analysis following the work of Michel Foucault has become a valuable
      methodology in the critical analysis of a broad range of topics relating to
      health. However, it can be a daunting task, in that there seems to be both a huge
      number of possible approaches to carrying out this type of project, and an
      abundance of different, often conflicting, opinions about what counts as
      'Foucauldian'. This article takes the position that methodological design should
      be informed by ongoing discussion and applied as appropriate to a particular area
      of inquiry. The discussion given offers an interpretation and application of
      Foucault's methodological principles, integrating a reading of Foucault with
      applications of his work by other authors, showing how this is then applied to
      interrogate the practice of vocational rehabilitation. It is intended as a
      contribution to methodological discussion in this area, offering an
      interpretation of various methodological elements described by Foucault,
      alongside specific application of these aspects. 

PMID- 23117589
TI  - Exploring the PDE5 H-pocket by ensemble docking and structure-based design and
      synthesis of novel beta-carboline derivatives.
AB  - By studying the co-crystal information of interactions between PDE5 and its
      inhibitors, forty new tetrahydro-beta-carbolines based-analogues were
      synthesized, and tested for their PDE5 inhibition. Some compounds were as active
      as tadalafil in inhibiting PDE5 and of better selectivity profile particularly
      versus PDE11A, the nature of the terminal ring and its nitrogen substituent are
      the main determinants of selectivity. Ensemble docking confirmed the role of H
      loop closed conformer in activity versus its occluded and open forms.
      Conformational studies showed the effect of bulkiness of the terminal ring N
      alkyl substituent on the formation of stable enzyme ligands conformers. The
      difference in potencies of hydantoin and piperazinedione analogues, together with
      the necessity of C-5/C-6 R-absolute configuration has been revealed through
      molecular docking.

PMID- 23117591
TI  - Understanding context for quality improvement: artefacts, affordances and socio
      material infrastructure.
AB  - Against a backdrop of growing concern for patient safety and service quality,
      modern health-care systems are witnessing a proliferation of improvement
      initiatives. The impact is often variable, however, and a key theme to emerge
      from evaluations of these efforts is a recognition of the effects of local
      context on the success or otherwise of an intervention. However, the 'context'
      tends to be understood in terms of higher order issues such as structure, culture
      and leadership. This article explores a dimension of context not typically taken
      into account in the health-care improvement literature: the infrastructural
      context. Many quality improvement interventions hinge on the introduction of
      artefacts to support behavioural change in the workplace. Despite calls from
      scholars of technology in practice for a greater acknowledgement of the role of
      such mundane artefacts in supporting the organisation of health-care work, they
      are rarely considered in these terms in evaluations of improvement efforts. In
      this article, I argue that understanding the potential generative effects of
      artefacts for quality improvement purposes requires an understanding of their
      'affordances' and how these relate to the socio-material infrastructure into
      which they are to be introduced, and/or the technologies they are designed to
      replace. Integrated care pathway implementation is examined to illustrate this
      position. Drawing on qualitative case studies of integrated care pathway
      development processes undertaken in the UK National Health Service and
      ethnographic research on the international care pathway community, I consider the
      infrastructural reasons behind the challenges of making pathways work in
      organising health care, and why, contrary to the aspirations of their proponents,
      they often appear to increase rather than decrease paperwork. 

PMID- 23117592
TI  - Heteronormativity hurts everyone: experiences of young men and clinicians with
      sexually transmitted infection/HIV testing in British Columbia, Canada.
AB  - Heteronormative assumptions can negatively influence the lives of young gay and
      bisexual men, and recent sociological analyses have identified the negative
      impacts of heteronormativity on heterosexual men (e.g. 'fag discourse' targeted
      at heterosexual adolescents). However, insights into how heteronormative
      discourses may be (re)produced in clinical settings and how they contribute to
      health outcomes for gay, bisexual and heterosexual men are poorly understood.
      This analysis draws on in-depth interviews with 45 men (15-25 years old) and 25
      clinicians in British Columbia, Canada, to examine how heteronormative discourses
      affect sexually transmitted infection testing. The sexually transmitted
      infection/HIV testing experience emerged as a unique situation, whereby men's
      (hetero)sexuality was explicitly 'interrogated'. Risk assessments discursively
      linked sexual identity to risk in ways that reinforced gay men as the risky
      'other' and heterosexual men as the (hetero)normal and, therefore, relatively low
      risk patient. This, in turn, alleviated concern for sexually transmitted
      infection/HIV exposure in heterosexual men by virtue of their sexual identity
      (rather than their sexual practices), which muted discussions around their sexual
      health. The clinicians also positioned sexual identities and practices as
      important 'clues' for determining their patients' social contexts and supports
      while concurrently informing particular tailored clinical communication
      strategies. These findings highlight how men's experiences with sexually
      transmitted infection/HIV testing can (re)produce heteronormative assumptions and
      expectations or create opportunities for more equitable gendered relations and
      discourses. 

PMID- 23117593
TI  - New nanoformulation of rapamycin Rapatar extends lifespan in homozygous p53-/-
      mice by delaying carcinogenesis.
AB  - The nutrient-sensing mTOR (mammalian Target of Rapamycin) pathway regulates
      cellular metabolism, growth functions, and proliferation and is involved in age
      related diseases including cancer, type 2 diabetes, neurodegeneration and
      cardiovascular disease. The inhibition of mTOR by rapamycin, or calorie
      restriction, has been shown to extend lifespan and delays tumorigenesis in
      several experimental models suggesting that rapamycin may be used for cancer
      prevention. This requires continuous long-term treatment making oral formulations
      the preferred choice of administration route. However, rapamycin by itself has
      very poor water solubility and low absorption rate. Here we describe
      pharmacokinetic and biological properties of novel nanoformulated micelles of
      rapamycin, Rapatar. Micelles of Rapatar were rationally designed to increase
      water solubility of rapamycin to facilitate oral administration and to enhance
      its absorption. As a result, bioavailability of Rapatar was significantly
      increased (up to 12%) compared to unformulated rapamycin, which concentration in
      the blood following oral administration remained below level of detection. We
      also demonstrated that the new formulation does not induce toxicity during
      lifetime administration. Most importantly, Rapatar extended the mean lifespan by
      30% and delayed tumor development in highly tumor-prone p53-/- mice. Our data
      demonstrate that water soluble Rapatar micelles represent safe, convenient and
      efficient form of rapamycin suitable for a long-term treatment and that Rapatar
      may be considered for tumor prevention.

PMID- 23117595
TI  - Health and economic consequences of fragile X syndrome for caregivers.
AB  - OBJECTIVE: To describe the health and economic burden experienced by caregivers
      of individuals with fragile X syndrome (FXS) and test the assumption that burden
      is associated with specific dimensions of problem behavior. METHODS: Three
      hundred fifty caregivers rated their son or daughter's problem behavior and
      reported the use of medical services, caregiving time, impact on employment,
      financial burden, caregiver injuries, caregiver mental health, and prescription
      drug use. RESULTS: The son's FXS posed a significant burden for caregivers in a
      number of areas. Visits to medical specialists were common for both males (5.4
      per year) and females (5.1 per year). Caregivers reported 9.2 hours per day of
      family caregiving for males with FXS and an additional 5.5 hours of paid help.
      Most families reported that FXS had at least some financial impact on the family,
      and caregivers had to take an average of 19.4 hours from work each month to care
      for their child's needs. Almost one third of the caregivers had been injured by
      their child at least once in the past year; when injuries occurred, the frequency
      was high (14.7 per year), of which 2.7 required medical care. Approximately one
      third of the caregivers had seen a professional for anxiety, stress, or
      depression during the past year, and one fourth were taking medication to help
      with these symptoms. Caregiver burden was highly associated with problem
      behavior, most commonly irritability. CONCLUSION: Problem behavior is a strong
      contributor to burden experienced by caregivers of children and adults with FXS.
      Clinicians should be aware of the role problem behavior plays in family
      adaptation and help families access appropriate medical and social support
      services.

PMID- 23117596
TI  - An examination of the relationship of anxiety and intelligence to adaptive
      functioning in children with chromosome 22q11.2 deletion syndrome.
AB  - OBJECTIVE: This study investigates the relationship between anxiety symptoms and
      adaptive function in children with chromosome 22q11.2 deletion syndrome
      (22q11.2DS). METHODS: Seventy-eight children between 7 and 14 years of age with
      22q11.2DS and 36 typically developing (TD) children without known genetic
      syndromes participated in a larger study of neurocognition. Parents completed
      questionnaires about their child's anxiety symptoms (Behavior Assessment System
      for Children, 2nd edition [BASC-2] and Spence Children's Anxiety Scale [SCAS])
      and adaptive functioning (BASC-2 and Adaptive Behavior Assessment System, 2nd
      edition). Within the 22q11.2DS group, different DSM-IV anxiety domains were also
      analyzed using SCAS subscales. RESULTS: Based on parent report, 19% of children
      with 22q11.2DS had a prior diagnosis of an anxiety disorder versus 58% with at
      least 1 elevated anxiety score (BASC-2 or SCAS). Mean BASC-2 anxiety scores were
      significantly higher in 22q11.2DS (55.6 +/- 12.5) than in TD children (48.3 +/-
      10; p = .003), and a greater percentage of children with 22q11.2DS (37%) had an
      elevated BASC-2 anxiety scores compared with TD children (14%; p = .01). Higher
      anxiety scores were related to lower adaptive function (r = -.27; p = .015), but
      there was no relationship between Wechsler Intelligence Scale for Children, 4th
      edition Full Scale Intelligence Quotient and BASC-2 adaptive skills (r = -.06; p
      = .6) in the 22q11.2DS group. For the individual SCAS anxiety subscales, panic
      agoraphobia (r = -.38; p = .03), physical injury (r = -.34; p = .05), and
      obsessive-compulsive disorder (r = -.47; p = .005) were significantly negatively
      related to adaptive function in 22q11.2DS. CONCLUSION: Despite the known risk,
      anxiety is underidentified in children with 22q11.2DS. The presence of anxiety
      symptoms, but not intelligence levels, in children with 22q11.2DS negatively
      correlated with adaptive function and impacts everyday living skills.

PMID- 23117598
TI  - Truancy is associated with sexual risk among early adolescents.
AB  - OBJECTIVE: While previous studies have identified relationships between school
      truancy and adolescent substance use risk, sexual risk remains unaddressed.
      METHODS: Urban early adolescents (mean age, 13.14 years) with mental health
      symptoms completed audio computer-assisted self-interviews regarding risk
      behaviors. RESULTS: Teens who reported a history of skipping school (n = 25),
      compared with those who did not (n = 113), indicated greater frequency of having
      ever engaged in oral, vaginal, and anal sex, as well as nonintercourse sexual
      behaviors. They also reported less value in remaining abstinent but did not
      demonstrate differences in HIV knowledge or school connectedness. CONCLUSION:
      Truancy may serve as an important marker for the early identification of youth at
      risk for unintended pregnancy or sexually transmitted diseases.

PMID- 23117599
TI  - Developmental coordination disorder plus:  a diagnosis by exclusion?
AB  - CASE: Cayden is a 6.3-year-old boy who you have been following in our practice
      since birth. He was born at 35.5 weeks at 6 pounds 4 ounces following a fraternal
      twin gestation. Both children were "on target" with their milestones, but Cayden
      did not seem to progress as quickly as his sister. He did not initiate play with
      his sister when they were toddlers and Cayden was the "shy" one.

PMID- 23117597
TI  - Associations between temperament at age 1.5 years and obesogenic diet at ages 3
      and 7 years.
AB  - OBJECTIVE: To investigate whether temperament in 1.5 year olds predicts their
      consumption of potentially obesogenic foods and drinks at 3 and 7 years of age.
      METHODS: Participants were 6997 mothers and infants from the Norwegian Mother and
      Child Cohort Study. Questionnaires were collected during pregnancy, at birth, and
      at 6 months and 1.5, 3, and 7 years of age. Predictor variables included
      children's temperament at 1.5 years of age (internalizing, externalizing,
      surgent) and mothers' negative affectivity. Outcome variables included children's
      consumption of sweet foods, sweet drinks, and fruits/vegetables at 3 and 7 years
      of age (dichotomized at the 85th percentile). RESULTS: Controlling for
      covariates, internalizing 1.5 year olds (anxious, dependent) were 77% and 63%
      more likely to consume sweet drinks daily at 3 and 7 years of age, respectively;
      they were 55% and 43% more likely to consume sweet foods daily at 3 and 7 years,
      respectively. Externalizing 1.5 year olds (hyperactive, aggressive) were 34% more
      likely to consume sweet drinks daily at 7 years of age; they were 39% and 44%
      more likely to consume sweet foods daily at 3 and 7 years, respectively, and they
      were 47% and 33% less likely to consume fruits/vegetables daily at 3 and 7 years
      of age, respectively. Surgent 1.5 year olds (active, sociable) were 197% and 78%
      more likely to consume 2 portions of fruits/vegetables daily at 3 and 7 years,
      respectively. The association of maternal negative affectivity was limited to the
      child's consumption of sweet foods at 3 and 7 years. CONCLUSION: Early child
      temperament is a risk factor for obesogenic diet in later childhood. Mechanisms
      explaining this association need to be explored.

PMID- 23117600
TI  - A microfluidic-based bubble generation platform enables analysis of physical
      property change in phospholipid surfactant layers by interfacial ozone reaction.
AB  - The air-liquid interface filled with pulmonary surfactant is a unique feature of
      our lung alveoli. The mechanical properties of this interface play an important
      role in breathing and its malfunction induced by an environmental hazard, such as
      ozone, relates to various lung diseases. In order to understand the interfacial
      physics of the pulmonary surfactant system, we employed a microfluidic bubble
      generation platform with a model pulmonary surfactant composed of two major
      phospholipids: DPPC (1,2-dipalmitoyl-sn-phosphatidylcholine) and POPG (1
      palmitoyl-2-oleoyl-sn-phosphatidylglycerol). With fluorescence imaging, we
      observed the ozone-induced chemical modification of the unsaturated lipid
      component of the lipid mixture, POPG. This chemical change due to the oxidative
      stress was further utilized to study the physical characteristics of the
      interface through the bubble formation process. The physical property change was
      evaluated through the oscillatory behaviour of the monolayer, as well as the
      bubble size and formation time. The results presented demonstrate the potential
      of this platform to study interfacial physics of lung surfactant system under
      various environmental challenges, both qualitatively and quantitatively.

PMID- 23117601
TI  - Microtubule dynamics alter the interphase nucleus.
AB  - Microtubules are known to drive chromosome movements and to induce nuclear
      envelope breakdown during mitosis and meiosis. Here we show that microtubules can
      enforce nuclear envelope folding and alter the levels of nuclear envelope
      associated heterochromatin during interphase, when the nuclear envelope is
      intact. Microtubule reassembly, after chemically induced depolymerization led to
      folding of the nuclear envelope and to a transient accumulation of condensed
      chromatin at the site nearest the microtubule organizing center (MTOC). This
      microtubule-dependent chromatin accumulation next to the MTOC is dependent on the
      composition of the nuclear lamina and the activity of the dynein motor protein.
      We suggest that forces originating from simultaneous polymerization of
      microtubule fibers deform the nuclear membrane and the underlying lamina. Whereas
      dynein motor complexes localized to the nuclear envelope that slide along the
      microtubules transfer forces and/or signals into the nucleus to induce chromatin
      reorganization and accumulation at the nuclear membrane folds. Thus, our study
      identified a molecular mechanism by which mechanical forces generated in the
      cytoplasm reshape the nuclear envelope, alter the intranuclear organization of
      chromatin, and affect the architecture of the interphase nucleus.

PMID- 23117603
TI  - Marinobacter nanhaiticus sp. nov., polycyclic aromatic hydrocarbon-degrading
      bacterium isolated from the sediment of the South China Sea.
AB  - A Gram-negative, rod-shaped, slightly halophilic and facultatively anaerobic
      bacterium, designated strain D15-8W(T), was isolated from the sediment of the
      South China Sea. Growth was found to occur optimally at 25  degrees C, between pH
      7.0 and 8.0 and with 1-5 % (w/v) NaCl. The strain was observed to utilize a
      variety of organic substrates and polycyclic aromatic hydrocarbons as sole carbon
      sources. The G+C content of the genomic DNA was determined to be 58.7 %. The
      predominant respiratory quinone was found to be Q-9. The significant fatty acids
      were determined to be C(16:0), C(16:1) omega9c, C(18:1) omega9c, C(12:0) and
      C(14:0) 3OH. Analysis of 16S rRNA gene sequences showed that strain D15-8W(T)
      fits within the phylogenetic cluster of the genus Marinobacter and is most
      closely related to Marinobacter segnicrescens CGMCC 1.6489(T), Marinobacter
      bryozoorum DSM 15401(T), Marinobacter lacisalsi CECT 7297(T) and Marinobacter
      daqiaonensis CGMCC1.9167(T). The DNA-DNA hybridization values between strain D15
      8W(T) and the type strains of the most closely related species were 42.3 % (CGMCC
      1.6489(T)), 39.8 % (DSM 15401(T)), 37.3 % (CECT 7297(T)) and 35.2 %
      (CGMCC1.9167(T)). The results of this polyphasic study indicate that strain D15
      8W(T) represents a novel species of the genus Marinobacter, for which the name
      Marinobacter nanhaiticus sp. nov. is proposed. The type strain is D15-8W(T)
      (=CGMCC 1.11019(T)=KCTC 23749(T)).

PMID- 23117602
TI  - Short-term use of adaptive servo ventilation improves renal function in heart
      failure patients with sleep-disordered breathing.
AB  - Sleep-disordered breathing (SDB) deteriorates the prognosis of patients with
      chronic heart failure (CHF). Adaptive servo ventilation (ASV) is a new
      therapeutic modality to treat SDB including Cheyne-Stokes respiration associated
      with central sleep apnea. Renal function plays critical roles in the progression
      of CHF and is a strong predictor of clinical outcomes. Cystatin C is a marker of
      renal function, and more sensitive than serum creatinine. The purpose of the
      present study was to examine whether ASV is effective for cardiac overload and
      renal dysfunction in CHF patients with SDB. Fifty patients with CHF and SDB (mean
      left ventricular ejection fraction 34.0 %, estimated glomerular filtration rate
      (eGFR) 62.8 ml/min/1.73 cm(2)) were examined. We performed polysomnography for
      two consecutive days (baseline and on ASV), and measured levels of serum N
      terminal-pro B-type natriuretic peptide (NT-pro BNP), cystatin C, and estimated
      glomerular filtration rate based on cystatin C (eGFR Cyst C). ASV significantly
      improved the apnea hypopnea index, central apnea index, obstructive apnea index,
      arousal index, mean SPO2, and lowest SPO2 compared to baseline. ASV decreased NT
      pro BNP (1,109.0 (2,173.2) to 912.8 (1,576.7) pg/ml, p < 0.05), cystatin C (1.391
      +/- 0.550-1.348 +/- 0.489 mg/l, p < 0.05), and increased eGFR Cyst C (61.9 +/-
      30.8-65.7 +/- 33.8 ml/min/1.73 cm(2), p < 0.01). ASV improved SDB, reduced
      cardiac overload, and ameliorated renal function in CHF patients with SDB. ASV
      has short-term beneficial effects on not only SDB but also cardio-renal function.
      ASV might be a promising useful tool for CHF as an important non-pharmacotherapy
      with cardio-renal protection. 

PMID- 23117604
TI  - Quantitative histological analysis of the mandibular branch of the facial nerve
      in rats.
AB  - PURPOSE: To establish a model to quantitative histological analysis of the
      mandibular branch of the facial nerve in rats. METHODS: Eleven Wistar rats had
      their right and left mandibular branches of the facial nerve surgically removed
      and were sacrificed afterwards. Quantitative histological analysis was performed
      with: a) partial number of axons; b) partial area of the transversal cut of the
      nerve (9000 MUm(2)); c) partial density. The averages of partial density were
      obtained. The statistical study was established by Wilcoxon test (p=0.05).
      RESULTS: In relation to density of axons, comparison between sides shows no
      statistically significant difference (p=0.248; p=0.533). Mean partial density of
      distal and proximal samples was, respectively, 0.18 +/- 0.02 and 0.19 +/- 0.02
      axons/MUm(2). Comparison between proximal and distal samples shows no
      statistically significant difference (p=0.859; p=0.182). CONCLUSION: This study
      has successfully established a model to histological quantitative analysis of the
      mandibular branch of the facial nerve in rats.

PMID- 23117605
TI  - Is there a relationship between lipids metabolism and splenic surgeries?
AB  - PURPOSE: To assess the influence of spleen surgeries (splenectomy, presence of
      spleen and after conservative surgeries) on lipids metabolism. METHODS: Fifty
      female Wistar rats of similar weight and age were divided into five groups
      submitted to the following procedures: Group 1 - control, with an intact spleen;
      Group 2 - sham operation, Group 3 - total splenectomy; Group 4 - subtotal
      splenectomy, and Group 5 - total splenectomy complemented with autogenous spleen
      tissue implants. Four months after the interventions, serum triglycerides, total
      cholesterol and fractions (VLDL-cholesterol, LDL-cholesterol, HDL-cholesterol)
      were determined. The results for the four groups were compared by analysis of
      variance followed by the Tukey-Kramer test, with the level of significance set at
      p<0.05. RESULTS: There were no differences between groups 1, 2, 4 and 5. In the
      animals submitted to total splenectomy, total cholesterol (p=0.0151) and LDL
      cholesterol fraction concentrations (p<0.0001) were higher, whereas HDL
      cholesterol fraction concentrations were lower (p=0.0026) than those detected in
      the other groups. There was no difference in triglycerides (p=0.1571) or VLDL
      cholesterol (p=0.2527) between groups. CONCLUSION: Splenectomy is related to
      changes in the lipid metabolism that are reverted by autogenous spleen tissue
      implants.

PMID- 23117606
TI  - Is a 5 mm rat calvarium defect really critical?
AB  - PURPOSE: To evaluate bone regeneration in critical defects in the rats'
      calvarium. METHODS: Eighteen rats Wistar were divided into three groups of six
      animals each according to the time of evaluation (15, 30 and 60 days). One
      calvarium defect of 5 mm was made in the parietal bone of each animal under
      general anesthesia. After the time of evaluation, the animals were killed, when
      the bone was histological studied and classified according to the type of tissue
      found: fibrosis or bone. RESULTS: The results showed that in the group of 15
      days, in five animals there was only fibrosis. In the group of 30 days, the
      process of regeneration was growing and in four animals was found bone, in three
      with partial filling and in the other one with complete filling of the defect. In
      the group of 60 days, out of the three animals with bone, two had a complete
      filling of the defect. CONCLUSIONS: There was no bone regeneration in critical
      defects in 15 days. There was regeneration in the most part of the animals in 30
      and 60 days.

PMID- 23117607
TI  - Wound healing using ionic silver dressing and nanocrystalline silver dressing in
      rats.
AB  - PURPOSE: To investigate the results of the healing process on surgical wounds in
      the back of Wistar rats using nanocristaline and ionic silver dressing. METHODS:
      Sixty rats Wistar were submitted to surgical wounds with punch of 8 mm in
      diameter. In 30 animals (groups PN - nanocristaline and AD - control) two
      surgical wounds were done diametrically opposite on the upper back side. On the
      right side was used nanocristaline (PN) silver dressing and on the left side,
      distilled water dressing (AD). On the other group of 30 rats, only one wound was
      made with the punch, on the right side, and was used ionic silver dressing. So,
      the groups were divided into three subgroups, according to the day of death
      (7(th), 14(th) and 21(st) day). In each of these days the wounds diameter were
      measured to evaluate the wound contraction. Microscopic data were analyzed using
      the H&E staining to verify the inflammatory process and neovascularization. The
      Masson trichrome staining was used to verify the fibrosis. RESULTS:
      Macroscopically only the subgroup of 21(st) day showed statistical significance;
      between the groups AD and PI inflammatory process appeared in the 7(th) day
      subgroup in 90% of the cases. In neovascularization there was statistical
      significance between the groups PN and AD in the subgroup of 7(th) day. Fibrosis
      did not show statistical significance in the studied groups. CONCLUSIONS: In
      relation to wound contraction, PN and PI groups showed better results than the AD
      group. In regard to histological analysis, H&E staining showed that there was
      presence of inflammation in all groups, and at the end, the control group (AD) on
      7(th) day, was superior to PN and PI groups. In relationship to fibrosis, no
      differences were obtained among groups.

PMID- 23117608
TI  - 0.1T magnetic resonance image in the study of experimental hydrocephalus in rats.
      Accuracy of the method in the measurements of the ventricular size.
AB  - PURPOSE: To investigate the accuracy of 1.0T Magnetic Resonance Imaging (MRI) to
      measure the ventricular size in experimental hydrocephalus in pup rats. METHODS:
      Wistar rats were subjected to hydrocephalus by intracisternal injection of 20%
      kaolin (n=13). Ten rats remained uninjected to be used as controls. At the
      endpoint of experiment animals were submitted to MRI of brain and killed. The
      ventricular size was assessed using three measures: ventricular ratio (VR), the
      cortical thickness (Cx) and the ventricles area (VA), performed on photographs of
      anatomical sections and MRI. RESULTS: The images obtained through MR present
      enough quality to show the lateral ventricular cavities but not to demonstrate
      the difference between the cortex and the white matter, as well as the details of
      the deep structures of the brain. There were no statistically differences between
      the measures on anatomical sections and MRI of VR and Cx (p=0.9946 and p=0.5992,
      respectively). There was difference between VA measured on anatomical sections
      and MRI (p<0.0001). CONCLUSION: The parameters obtained through 1.0T MRI were
      sufficient in quality to individualize the ventricular cavities and the cerebral
      cortex, and to calculate the ventricular ratio in hydrocephalus rats when
      compared to their respective anatomic slice.

PMID- 23117609
TI  - Oxidative stress gene expression profile in inbred mouse after
      ischemia/reperfusion small bowel injury.
AB  - PURPOSE: To determine the profile of gene expressions associated with oxidative
      stress and thereby contribute to establish parameters about the role of enzyme
      clusters related to the ischemia/reperfusion intestinal injury. METHODS: Twelve
      male inbred mice (C57BL/6) were randomly assigned: Control Group (CG) submitted
      to anesthesia, laparotomy and observed by 120 min; Ischemia/reperfusion Group
      (IRG) submitted to anesthesia, laparotomy, 60 min of small bowel ischemia and 60
      min of reperfusion. A pool of six samples was submitted to the qPCR-RT protocol
      (six clusters) for mouse oxidative stress and antioxidant defense pathways.
      RESULTS: On the 84 genes investigated, 64 (76.2%) had statistic significant
      expression and 20 (23.8%) showed no statistical difference to the control group.
      From these 64 significantly expressed genes, 60 (93.7%) were up-regulated and 04
      (6.3%) were down-regulated. From the group with no statistical significantly
      expression, 12 genes were up-regulated and 8 genes were down-regulated.
      Surprisingly, 37 (44.04%) showed a higher than threefold up-regulation and then
      arbitrarily the values was considered as a very significant. Thus, 37 genes
      (44.04%) were expressed very significantly up-regulated. The remained 47 (55.9%)
      genes were up-regulated less than three folds (35 genes - 41.6%) or down
      regulated less than three folds (12 genes - 14.3%). CONCLUSION: The intestinal
      ischemia and reperfusion promote a global hyper-expression profile of six
      different clusters genes related to antioxidant defense and oxidative stress.

PMID- 23117610
TI  - Effects of cilostazol in kidney and skeletal striated muscle of Wistar rats
      submitted to acute ischemia and reperfusion of hind limbs.
AB  - PURPOSE: To investigate the effect of cilostazol, in kidney and skeletal muscle
      of rats submitted to acute ischemia and reperfusion. METHODS: Fourty three
      animals were randomized and divided into two groups. Group I received a solution
      of cilostazol (10 mg/Kg) and group II received saline solution 0.9% (SS) by
      orogastric tube after ligature of the abdominal aorta. After four hours of
      ischemia the animals were divided into four subgroups: group IA (Cilostazol): two
      hours of reperfusion. Group IIA (SS): two hours of reperfusion. Group IB
      (Cilostazol): six hours of reperfusion. Group IIB (SS) six hours of reperfusion.
      After reperfusion, a left nephrectomy was performed and removal of the muscles of
      the hind limb. The histological parameters were studied. In kidney cylinders of
      myoglobin, vacuolar degeneration and acute tubular necrosis. In muscle
      interstitial edema, inflammatory infiltrate, hypereosinophilia fiber,
      cariopicnose and necrosis. Apoptosis was assessed by immunohistochemistry for
      cleaved caspase-3 and TUNEL. RESULTS: There was no statistically significant
      difference between groups. CONCLUSION: Cilostazol had no protective effect on the
      kidney and the skeletal striated muscle in rats submitted to acute ischemia and
      reperfusion in this model.

PMID- 23117611
TI  - Comparative study between fibrin glue and platelet rich plasma in dogs skin
      grafts.
AB  - PURPOSE: Compare fibrin glue (Tissucol((r))) and platelet-rich plasma in full
      thickness mesh skin grafts in dogs. METHODS: Eighteen dogs were used, divided
      into two groups: fibrin glue (FG) and platelet-rich plasma (PRP). In all the
      animals, a full-thickness 3x3 cm mesh skin graft was implanted. In the left limb,
      the biomaterial was place between the graft and the receptor bed, according to
      the group, while the right limb served as the control group. All the animals were
      evaluated clinically every 48 hours until the 14th day, using the variables of
      exudation, coloration, edema and cosmetic appearance. Three animals were
      evaluated histologically, on the third, seventh and tenth postoperative days,
      using the variables of fibroblasts, collagen, granulation tissue, microscopic
      integration-adherence and acute inflammation. RESULTS: Clinical evaluations
      showed that the group CF showed better scores for all variables compared to PRP
      group. On the histological evaluations PRP group had a higher presence of
      fibroblasts in the seventh and fourteenth days. CONCLUSION: The fibrin glue group
      was clinically superior to the platelet-rich group when used on full-thickness
      skin grafts in dogs.

PMID- 23117612
TI  - Effects of aspirin on mesenteric lymph nodes of rabbits as basis for its use on
      lymph nodes metastases.
AB  - PURPOSE: To evaluate the effects of aspirin 10% and 20% on mesenteric lymph nodes
      of rabbits as basis for its use on lymph nodes metastases. METHODS: A total of 20
      lymph nodes from 20 rabbits (randomized in four groups) were evaluated. Aspirin
      solutions 10% (groups A and C) and 20% (groups B and D) were injected into
      mesenteric lymph nodes of healthy rabbits and had its gross and histological
      effects evaluated at 24 hours (groups A and B) and at seven days (groups C and
      D). RESULTS: In the groups A and B evaluated at 24 hours it was observed
      extensive necrosis and hemorrhage, a significant increase in apoptosis throughout
      the lymph node with medullary sinuses enlargement and an increase in germinal
      centers. In the groups C and D evaluated at seven days of solution injection
      there was also an increase in apoptosis with higher elevation of histiocytes and
      a significant decrease of necrosis and an increase of giant cells was noticed
      causing a foreign body chronic inflammation. In all comparisons, there were no
      differences between the concentrations used (10 and 20%). CONCLUSIONS: The
      injection of aspirin on lymph nodes caused necrosis and an increase of apoptosis
      after 24 hours and after seven days of treatment there was regeneration of the
      lymph nodes, with intense decrease of necrosis and a great elevation of
      apoptosis. These experimental results support future clinical studies on
      application of aspirin in the treatment of lymphatic metastases, since the
      increase of apoptosis is one of the pillars of cancer therapy.

PMID- 23117613
TI  - Postoperative kidney injury does not decrease survival after liver
      transplantation.
AB  - PURPOSE: To explore the effect of acute kidney injury (AKI) on long-term survival
      after conventional orthotopic liver transplantation (OLT) without venovenous
      bypass (VVB). METHODS: A retrospective cohort study was carried out on 153
      patients with end-stage liver diseases transplanted by the Department of General
      Surgery and Liver Transplantation of the University of Pernambuco, from August,
      1999 to December, 2009. The Kaplan-Meier survival estimates and log-rank test
      were applied to explore the association between AKI and long-term patient
      survival, and multivariate analyses were applied to control the effect of other
      variables. RESULTS: Over the 12.8-year follow-up, 58.8% patients were alive with
      a median follow-up of 4.5-year. Patient 1-, 2-, 3- and 5-year survival were
      74.5%, 70.6%, 67.9% and 60.1%; respectively. Early postoperative mortality was
      poorer amongst patients who developed AKI (5.4% vs. 20%, p=0.010), but long-term
      5-year survival did not significantly differed between groups (51.4% vs. 65.3%;
      p=0.077). After multivariate analyses, AKI was not significantly related to long
      term survival and only the intraoperative transfusion of red blood cells was
      significantly related to this outcome (non-adjusted Exp[b]=1.072; p=0.045).
      CONCLUSION: The occurrence of postoperative acute kidney injury did not
      independently decrease patient survival after orthotopic liver transplantation
      without venovenous bypass in this data from northeast Brazil.

PMID- 23117614
TI  - Portland cement with additives in the repair of furcation perforations in dogs.
AB  - PURPOSE: To evaluate the use of Portland cements with additives as furcation
      perforation repair materials and assess their biocompatibility. METHODS: The four
      maxillary and mandibular premolars of ten male mongrel dogs (1-1.5 years old,
      weighing 10-15 kg) received endodontic treatment (n=80 teeth). The furcations
      were perforated with a round diamond bur (1016 HL). The perforations involved the
      dentin, cementum, periodontal ligament, and alveolar bone. A calcium sulfate
      barrier was placed into the perforated bone to prevent extrusion of obturation
      material into the periradicular space. The obturation materials MTA (control),
      white, Type II, and Type V Portland cements were randomly allocated to the teeth.
      Treated teeth were restored with composite resin. After 120 days, the animals
      were sacrificed and samples containing the teeth were collected and prepared for
      histological analysis. RESULTS: There were no significant differences in the
      amount of newly formed bone between teeth treated with the different obturation
      materials (p=0.879). CONCLUSION: Biomineralization occurred for all obturation
      materials tested, suggesting that these materials have similar biocompatibility.

PMID- 23117615
TI  - Effect of renal denervation procedure on left ventricular hypertrophy of
      hypertensive rats and its mechanisms.
AB  - PURPOSE: To investigate the effect of renal denervation (RDN) on the blood
      pressure, left ventricular hypertrophy and myocardial expression of TLR4/NF
      kappaB in spontaneously hypertensive rats (SHR). METHODS: A total of 36 SHR were
      randomly assigned into control group (D0), RDN group (D) and sham group (S). 12
      WKY rats of same age served as controls (WKY group). Rats in the D0 and WKY
      groups were sacrificed, but rats in the D and S group were sacrificed at one week
      and six weeks after surgery. The heart was collected and the left ventricle
      weighted followed by calculation of left ventricular mass index (LVMI). RESULTS:
      In the D0 group, the blood pressure, LVMI and protein expression of TLR4, NF
      kappaB, TNF-alpha and IL-6 in the myocardium were markedly higher than that in
      the WKY group (p<0.05). In the D1 and D2 group, the LVMI, NE and protein
      expression of TLR4, NF-kappaB, TNF-alpha and IL-6 in the myocardium were
      significantly reduced (p<0.05). CONCLUSION: Renal denervation can significantly
      delay the progression of left ventricular hypertrophy in spontaneously
      hypertensive rats, which may be attributed to the not only the suppression of
      sympathetic activity and attenuation of pressure load but the improvement of
      myocardial immuno-inflammation.

PMID- 23117616
TI  - Laryngeal and voice disorders in patients with gastroesophageal symptoms.
      Correlation with pH-monitoring.
AB  - PURPOSE: To investigate laryngeal and voice disorders in patients with
      gastroesophageal symptoms and their correlation with pH-monitoring. METHODS: A
      prospective study was carried out in patients attended at the Voice Disorder
      Outpatient Clinics of Botucatu Medical School in a five-year period and had vocal
      and gastroesophagic symptoms. Patients underwent videolaryngoscopy, auditory
      perceptual vocal analyses, computerized acoustic vocal analysis and dual probe pH
      monitoring for 24 hours. RESULTS: Fifty-seven patients were included (aged
      between 21 and 65 years; 45 women and 12 men), 18 had normal (31.6%) and 39 had
      abnormal pH-monitoring results (68.4%). Videolaryngoscopy recorded several
      laryngeal lesions for both patients with normal and abnormal pH-monitoring, but
      mostly for the latter group, highlighting posterior pachyderma. Auditory
      perceptual vocal assessments identified vocal changes of several intensities for
      both groups but especially for patients with abnormal pH-monitoring results. All
      acoustic parameters, except f0, were abnormal for both groups, compared to the
      control population. CONCLUSION: Acoustic and perceptual vocal changes and
      laryngeal lesions were recorded for both patients with normal pH-monitoring
      results and patients with abnormal pH-monitoring results, evidencing the
      importance of clinical history and videolaryngoscopic findings for diagnosing
      acid laryngitis.

PMID- 23117617
TI  - Chromosomally-retained RNA mediates homologous pairing.
AB  - Pairing and recombination of homologous chromosomes are essential for ensuring
      correct segregation of chromosomes in meiosis. In S. pombe, chromosomes are first
      bundled at the telomeres (forming a telomere bouquet) and then aligned by
      oscillatory movement of the elongated "horsetail" nucleus. Telomere clustering
      and subsequent chromosome alignment promote pairing of homologous chromosomes.
      However, this telomere-bundled alignment of chromosomes cannot be responsible for
      the specificity of chromosome pairing. Thus, there must be some mechanism to
      facilitate recognition of homologous partners after telomere clustering. Recent
      studies in S. pombe have shown that RNA transcripts retained on the chromosome,
      or RNA bodies, may play a role in recognition of homologous chromosomes for
      pairing. Acting as fiducial markers of homologous loci they would abrogate the
      need for direct DNA sequence homology searching.

PMID- 23117619
TI  - Phase II study of neoadjuvant anastrozole and concurrent radiotherapy for
      postmenopausal breast cancer patients.
AB  - BACKGROUNDS: The aim of this study was to assess the efficacy and safety of
      neoadjuvant anastrozole and radiation in postmenopausal breast cancer patients
      with hormone-receptor-positive tumors. In addition, we assessed the predictive
      factors for clinical and pathological response for concurrent anastrozole and
      radiotherapy. METHODS: Patients with tumors 3 cm or larger were treated with
      neoadjuvant anastrozole for 24 weeks, and concurrent radiation was administered
      from 12 weeks after the start of anastrozole. Core biopsies were obtained at
      baseline and 12 weeks after the start of anastrozole. After completing
      neoadjuvant treatment, patients underwent definitive surgery. The primary
      endpoint was the overall objective response. In addition, we assessed the
      predictive factors for clinical and pathological response for concurrent
      anastrozole and radiotherapy. This trial is registered with the UMIN Clinical
      Trials Registry, no. UMIN000002266. RESULTS: The overall objective response rate
      was 92 %. Toxicity during neoadjuvant therapy was acceptable, with no grade 3
      toxicities. After surgery, grade 3 toxicities occurred in 2 of 25 patients (8 %).
      CONCLUSIONS: Our preliminary data suggest that neoadjuvant anastrozole and
      radiation therapy in postmenopausal breast cancer patients with hormone-receptor
      positive tumors has a high potential for clinical response.

PMID- 23117620
TI  - Ferulic acid induces mammalian target of rapamycin inactivation in cultured
      mammalian cells.
AB  - Ferulic acid (FA), a naturally occurring polyphenol abundant in vegetables and
      rice bran, is known to possess a potent antioxidant activity, thereby protecting
      cells from oxidative stress. In the present study, we show that in addition to
      its known anti-oxidant activity, ferulic acid exerts substantial inhibitory
      activity on cellular mammalian target of rapamycin (mTor)-signaling pathways. In
      HeLa cells and mouse primary hepatocytes cultured with conventional nutrient-rich
      media, ferulic acid (1 mM) elicited dephosphorylation of S6 kinase and its
      substrate ribosomal S6. The dephosphorylating activity of ferulic acid was almost
      comparable to that of rapamycin, an established mTor inhibitor (TORC1). We next
      investigated the effect of ferulic acid on autophagy, a major cellular
      degradative process, which significantly contributes to the maintenance of cell
      homeostasis. Using a conventional green fluorescent protein-microtubule
      associated protein IA/IB light chain 3 (GFP-LC3) dot assay to evaluate autophagy
      flux, we showed that ferulic acid caused a significant increase in GFP-LC3 dots
      under serum-rich conditions in HeLa cells. The enhancement of autophagic flux by
      ferulic acid was almost equivalent to that of rapamycin. Furthermore, ferulic
      acid significantly enhanced autophagic degradation of (14)C-leucine-labeled long
      lived proteins of cultured mouse hepatocytes under nutrient-rich conditions, but
      not nutrient-deprived conditions. These results indicate that ferulic acid is
      almost the equivalent of rapamycin in the ability to inhibit mTor (TORC1), which
      makes it a potent activator of basal autophagy.

PMID- 23117622
TI  - Effect of micronutrient supplementation around calving on the plasma cortisol
      levels of Murrah buffaloes and Sahiwal and Karan Fries cows.
AB  - Micronutrients when fed around peripartum may reduce the stress induced by
      cortisol. With this objective, 24 Sahiwal (SW) and 24 Karan Fries (KF) cows and
      24 Murrah (Mu) buffaloes were taken and divided into four groups of six each.
      Vitamin E (VE), zinc (Zn) and copper were supplemented from 30 days pre- to 30
      days postcalving in groups 1, 2 and 3. Animals without supplementation served as
      control. Blood sampling was done on days 30, 15, 7 and 3 precalving; at calving;
      and on days 3, 7, 15 and 30 postcalving. Plasma cortisol levels were measured by
      ELISA. Supplementation of VE and Zn significantly (P<0.05) reduced plasma
      cortisol levels at calving and at 30 days postcalving. KF cows exhibited best
      results with VE, whereas SW cows and Mu buffaloes responded best to Zn. Copper
      increased the peripartum cortisol levels. Reduction in cortisol levels may help
      in keeping the animal healthy and stronger to fight immuno-suppression generally
      observed around the period of peripartum.

PMID- 23117621
TI  - Risk factor analysis for antibodies to Brucella, Leptospira and C. burnetii among
      cattle in the Adamawa Region of Cameroon: a cross-sectional study.
AB  - Brucellosis, leptospirosis and Q fever are important livestock diseases, commonly
      responsible for significant production losses, yet their epidemiology in sub
      Saharan Africa is largely unknown. Animal reservoirs pose the main risk of
      transmission to humans, where serious disease can occur. In the developing world
      setting, the flu-like symptoms of the acute stages of these diseases can be
      misdiagnosed as malaria, which can result in the administration of the wrong
      treatment, prolonged disease and increase in antibiotic resistance. Multivariable
      mixed-effects logistic regression models in this study revealed potential risk
      factors associated with the aforementioned pathogens in cattle in the Adamawa
      Region of Cameroon, with wildlife, namely, buffaloes, playing a major role in
      both Brucella and Coxiella burnetii seropositivity. Cattle mixing with other
      herds at night and cattle grazing in an area on a route taken by herds on
      transhumance appear to be positively associated with Leptospira seropositivity,
      while female cows and whether buffaloes are seen during grazing or transhumance
      are positively associated with C. burnetii seropositivity. On the other hand,
      animals that have been on transhumance in the past year and animals belonging to
      herdsmen of the Fulbe ethnic group appear to be protected against Leptospira and
      C. burnetii, respectively. Cattle of more than 2 years old appear to have
      increased odds of being seropositive to either pathogen. Further research is
      needed to confirm these findings and improve the knowledge of the epidemiology of
      these three pathogens in Africa, taking particular consideration of the wildlife
      involvement in the disease transmission.

PMID- 23117623
TI  - Pollen factors controlling self-incompatibility strength in Japanese pear.
AB  - Japanese pear has a genetically controlled self-incompatibility system, but both
      the pollen-tube growth in a semi in vivo assay and fruit set after self
      pollination differ considerably among cultivars. The percentage of styles in
      which pollen tubes have reached the base ranges from 0 to 36 %, a value
      determined by culture of styles in vitro, and fruit set ranges from 0.6 to 15.2
      %. Based on these data, we have assigned a value for the self-incompatibility
      weakness to each cultivar. Here, we showed that pollen factors control the degree
      of self-incompatibility. When the pollen-tube growth of 13 cultivars was compared
      in a completely compatible 'Hougetsu' (S (1) S (7)) style, it differed a fair
      amount among cultivars and showed a significantly positive relation to self
      incompatibility weakness (r = 0.707). The degree of self-incompatibility of pear
      is, therefore, determined by pollen factor(s) unrelated to the S-locus. Although
      the fruit set and fruit growth of 'Hougetsu' were not affected by the pollen
      donor, a positive relationship was also observed between seed number and self
      incompatibility weakness (r = 0.972). However, in a style with no S-RNase
      production (genotype: S (4) (sm) S (4) (sm) ), the relationship disappeared (r =
      0.341) and pollen-tube growth was promoted by 12-36 % except in one cultivar.
      These results suggest that S-RNase functions as a cytotoxin on compatible pollen
      in a cultivar-dependent manner, and that the degree of inhibition is determined
      by pollen factor(s) unrelated to the S-locus. The pollen factor also functions on
      S-RNase in incompatible styles, resulting in a different degree of self
      incompatibility.

PMID- 23117624
TI  - Exploring spectroscopic and physicochemical properties of new fluorescent ionic
      liquids.
AB  - In the current study, spectroscopic and physicochemical properties of newly
      prepared ionic liquids were investigated. Ionic liquids were synthesized via a
      simple and straightforward route using a metathesis reaction of either N,N
      diethyl-p-phenylenediamine monohydrochloride or N-phenacylpyridinium bromide with
      bis(trifluoromethane)sulfonimide lithium in water. High yield and purity were
      obtained for the resultant ionic liquids. Data acquired by use of (1)H NMR and FT
      IR measurements were consistent with the chemical structures of newly prepared
      ionic liquids. Results of thermal gravimetric analysis also implied that these
      ionic liquids have good thermal stability. In addition, UV-vis and fluorescence
      spectroscopy measurements provided that new ionic liquids are good absorbent and
      fluorescent. Time-based fluorescence steady-state measurements showed that ionic
      liquids have high photostability against photobleaching. For a deeper mechanistic
      understanding of the analytical potential of newly synthesized ionic liquids,
      spectroscopic and physicochemical parameters, including singlet absorption,
      extinction coefficient, fluorescence quantum yield, Stokes shift, oscillator
      strength and dipole moment, were also investigated.

PMID- 23117625
TI  - Mononuclear Co(III) and Ni(II) complexes with polypyridyl ligands,
      [Co(phen)2(taptp)]3+ and [Ni(phen) 2(taptp)]2+: synthesis, photocleavage and DNA
      binding.
AB  - Two novel, mixed ligand complexes of cobalt(III) and nickel(II),
      [Co(phen)2(taptp)](3+) (1) and [Ni(phen)2(taptp)](2+) (2) (phen = 1,10
      phenanthroline and taptp = 4,5,9,18-tetraazaphenanthreno [9,10-b]triphenylene),
      were synthesized and characterized by elemental analyses, UV-visible and NMR
      spectroscopies. The binding interactions of the two complexes with DNA have been
      investigated using absorption and emission spectroscopy methods and
      electrophoresis measurement mode. The intrinsic binding constants for these
      complexes to DNA are in the order of 10(5). In Tris buffer, the Co(III) complex
      shows a moderate luminescence which was enhanced after binding to DNA. However
      for complex Ni(II), no emission was observed in Tris buffer. The
      [Co(phen)2(taptp)](3+) and [Ni(phen)2(taptp)](2+) can cause the photocleavage of
      DNA supercoiled pBR322 upon irradiation by 360 nm light. Based on the data, an
      intercalative mode of DNA binding is suggested for the two complexes.

PMID- 23117627
TI  - A ciliary body tumor preventing angle closure.
AB  - We present a case report of a 60-year-old white woman, found to have advanced
      angle closure glaucoma in the right eye and appositional closure for about half
      of the left eye and no glaucoma. The remaining angle of the left eye was open
      with localized heavy pigmentation of the ciliary body band and trabecular
      meshwork. Ultrasound biomicroscopy showed a ciliary body tumor displacing the
      iris root centripetally preventing angle closure. 

PMID- 23117626
TI  - NF90 coordinately represses the senescence-associated secretory phenotype.
AB  - A hallmark trait of cellular senescence is the acquisition of a senescence
      associated secretory phenotype (SASP). SASP factors include cytokines and their
      receptors (IL-6, IL-8, osteoprotegerin, GM-CSF), chemokines and their ligands
      (MCP-1, HCC4), and oncogenes (Gro1 and Gro2), many of them encoded by mRNAs whose
      stability and translation are tightly regulated. Using two models of human
      fibroblast senescence (WI-38 and IDH4 cells), we report the identification of RNA
      binding protein NF90 as a post-transcriptional repressor of several SASP factors.
      In 'young', proliferating fibroblasts, NF90 was highly abundant, associated with
      numerous SASP mRNAs, and inhibited their expression. By contrast, senescent cells
      expressed low levels of NF90, thus allowing SASP factor expression to increase.
      NF90 elicited these effects mainly by repressing the translation of target SASP
      mRNAs, since silencing NF90 did not increase the steady-state levels of SASP
      mRNAs but elevated key SASP factors including MCP-1, GROa, IL-6, and IL-8. Our
      findings indicate that NF90 contributes to maintaining low levels of SASP factors
      in non-senescent cells, while NF90 reduction in senescent cells allows SASP
      factor expression to rise.

PMID- 23117628
TI  - Long-term results of laparoscopy-assisted radical right hemicolectomy with D3
      lymphadenectomy: clinical analysis with 177 cases.
AB  - PURPOSES: To study the feasibility, safety, and short-/long-term outcomes of
      laparoscopy-assisted right hemicolectomy with D3 lymphadenectomy for colon
      cancer. METHODS: The clinical data of 177 cases that underwent laparoscopy
      assisted radical right hemicolectomy with D3 lymphadenectomy for colon cancer
      between Jun 2003 and Sep 2010 was collected; the safety of operation, status of
      recovery, complication, oncological outcomes, and results of short-/long-term
      follow-up were analyzed. RESULTS: No case died in this study; five cases (2.82 %)
      were converted to open surgery. Four cases (2.26 %) underwent hand-assisted
      laparoscopic right hemicolectomy. The average operation time was 133 +/- 36 min,
      and the blood loss was 94 +/- 34 ml. The average time for passage of flatus,
      liquid food eating, and hospitalization were 2.1 +/- 0.7, 3.2 +/- 0.5, and 10.4
      +/- 2.7 day, respectively. The total number of lymph nodes removed was 15.2 +/-
      10.1. Postoperative complications were observed in 23 of 177 patients (12.99 %).
      The median follow-up period was 54 months; port-site recurrence was observed in
      one patient; local recurrence was found in five cases (2.82 %); distant
      metastasis was found in 21 cases (11.86 %). The cumulative overall survival of
      all stages at 12, 36, 60, and 72 months was 97.18 %, 83.73 %, 70.37 %, and 68.99
      %, respectively. The cancer-specific survival was 98.73 % (12 months), 87.81 %
      (36 months), and 80.17 % (60 months). CONCLUSIONS: Laparoscopy-assisted right
      hemicolectomy with D3 lymphadenectomy can be successfully performed for right
      colon cancer with the advantages of minimally invasive surgery. Moreover, the
      results implied appropriate short- and long-term outcomes.

PMID- 23117629
TI  - Fabrication and application of rose bengal-chitosan films in laser tissue repair.
AB  - Photochemical tissue bonding (PTB) is a sutureless technique for tissue repair,
      which is achieved by applying a solution of rose bengal (RB) between two tissue
      edges(1,2). These are then irradiated by a laser that is selectively absorbed by
      the RB. The resulting photochemical reactions supposedly crosslink the collagen
      fibers in the tissue with minimal heat production(3). In this report, RB has been
      incorporated in thin chitosan films to fabricate a novel tissue adhesive that is
      laser-activated. Adhesive films, based on chitosan and containing ~0.1 wt% RB,
      are fabricated and bonded to calf intestine and rat tibial nerves by a solid
      state laser (lambda=532 nm, Fluence~110 J/cm(2), spot size~0.5 cm). A single
      column tensiometer, interfaced with a personal computer, is used to test the
      bonding strength. The RB-chitosan adhesive bonds firmly to the intestine with a
      strength of 15 +/- 6 kPa, (n=30). The adhesion strength drops to 2 +/- 2 kPa
      (n=30) when the laser is not applied to the adhesive. The anastomosis of tibial
      nerves can be also completed without the use of sutures. A novel chitosan
      adhesive has been fabricated that bonds photochemically to tissue and does not
      require sutures.

PMID- 23117630
TI  - CardioPulse. A focused update to the ESC guidelines for the management of
      patients with atrial fibrillation.

PMID- 23117633
TI  - An office or your life.

PMID- 23117634
TI  - Development of a computerized adaptive test for depression.
AB  - CONTEXT Unlike other areas of medicine, psychiatry is almost entirely dependent
      on patient report to assess the presence and severity of disease; therefore, it
      is particularly crucial that we find both more accurate and efficient means of
      obtaining that report. OBJECTIVE To develop a computerized adaptive test (CAT)
      for depression, called the Computerized Adaptive Test-Depression Inventory (CAT
      DI), that decreases patient and clinician burden and increases measurement
      precision. DESIGN Case-control study. SETTING A psychiatric clinic and community
      mental health center. PARTICIPANTS A total of 1614 individuals with and without
      minor and major depression were recruited for study. MAIN OUTCOME MEASURES The
      focus of this study was the development of the CAT-DI. The 24-item Hamilton
      Rating Scale for Depression, Patient Health Questionnaire 9, and the Center for
      Epidemiologic Studies Depression Scale were used to study the convergent validity
      of the new measure, and the Structured Clinical Interview for DSM-IV was used to
      obtain diagnostic classifications of minor and major depressive disorder. RESULTS
      A mean of 12 items per study participant was required to achieve a 0.3 SE in the
      depression severity estimate and maintain a correlation of r = 0.95 with the
      total 389-item test score. Using empirically derived thresholds based on a
      mixture of normal distributions, we found a sensitivity of 0.92 and a specificity
      of 0.88 for the classification of major depressive disorder in a sample
      consisting of depressed patients and healthy controls. Correlations on the order
      of r = 0.8 were found with the other clinician and self-rating scale scores. The
      CAT-DI provided excellent discrimination throughout the entire depressive
      severity continuum (minor and major depression), whereas the traditional scales
      did so primarily at the extremes (eg, major depression). CONCLUSIONS Traditional
      measurement fixes the number of items administered and allows measurement
      uncertainty to vary. In contrast, a CAT fixes measurement uncertainty and allows
      the number of items to vary. The result is a significant reduction in the number
      of items needed to measure depression and increased precision of measurement.

PMID- 23117635
TI  - Familial confounding of the association between maternal smoking during pregnancy
      and offspring substance use and problems.
AB  - CONTEXT: Previous epidemiological, animal, and human cognitive neuroscience
      research suggests that maternal smoking during pregnancy (SDP) causes increased
      risk of substance use/problems in offspring. OBJECTIVE: To determine the extent
      to which the association between SDP and offspring substance use/problems depends
      on confounded familial background factors by using a quasi-experimental design.
      DESIGN: We used 2 separate samples from the United States and Sweden. The
      analyses prospectively predicted multiple indices of substance use and problems
      while controlling for statistical covariates and comparing differentially exposed
      siblings to minimize confounding. SETTING: Offspring of a representative sample
      of women in the United States (sample 1) and the total Swedish population born
      during the period from January 1, 1983, to December 31, 1995 (sample 2). PATIENTS
      OR OTHER PARTICIPANTS: Adolescent offspring of the women in the National
      Longitudinal Survey of Youth 1979 (n = 6904) and all offspring born in Sweden
      during the 13-year period (n = 1,187,360). MAIN OUTCOME MEASURES: Self-reported
      adolescent alcohol, cigarette, and marijuana use and early onset (before 14 years
      of age) of each substance (sample 1) and substance-related convictions and
      hospitalizations for an alcohol- or other drug-related problem (sample 2).
      RESULTS: The same pattern emerged for each index of substance use/problems across
      the 2 samples. At the population level, maternal SDP predicted every measure of
      offspring substance use/problems in both samples, ranging from adolescent alcohol
      use (hazard ratio [HR](moderate), 1.32 [95% CI, 1.22-1.43]; HR(high), 1.33 [1.17
      1.53]) to a narcotics-related conviction (HR(moderate), 2.23 [2.14-2.31];
      HR(high), 2.97 [2.86-3.09]). When comparing differentially exposed siblings to
      minimize genetic and environmental confounds, however, the association between
      SDP and each measure of substance use/problems was minimal and not statistically
      significant. CONCLUSIONS: The association between maternal SDP and offspring
      substance use/problems is likely due to familial background factors, not a causal
      influence, because siblings have similar rates of substance use and problems
      regardless of their specific exposure to SDP.

PMID- 23117637
TI  - Emotional reactivity to a single inhalation of 35% carbon dioxide and its
      association with later symptoms of posttraumatic stress disorder and anxiety in
      soldiers deployed to Iraq.
AB  - CONTEXT: The identification of modifiable predeployment vulnerability factors
      that increase the risk of combat stress reactions among soldiers once deployed to
      a war zone offers significant potential for the prevention of posttraumatic
      stress disorder (PTSD) and other combat-related stress disorders. Adults with
      anxiety disorders display heightened emotional reactivity to a single inhalation
      of 35% carbon dioxide (CO(2)); however, data investigating prospective linkages
      between emotional reactivity to CO(2) and susceptibility to war-zone stress
      reactions are lacking. OBJECTIVE: To investigate the association of soldiers'
      predeployment emotional reactivity to 35% CO(2) challenge with several indices of
      subsequent war-zone stress symptoms assessed monthly while deployed in Iraq.
      DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 158 soldiers with
      no history of deployment to a war zone were recruited from the Texas Combat
      Stress Risk Study between April 2, 2007, and August 28, 2009. MAIN OUTCOME
      MEASURES: Multilevel regression models were used to investigate the association
      between emotional reactivity to 35% CO(2) challenge (assessed before deployment)
      and soldiers' reported symptoms of general anxiety/stress, PTSD, and depression
      while deployed to Iraq. RESULTS: Growth curves of PTSD, depression, and general
      anxiety/stress symptoms showed a significant curvilinear relationship during the
      16-month deployment period. War-zone stressors reported in theater were
      associated with symptoms of general anxiety/stress, PTSD, and depression.
      Consistent with the prediction, soldiers' emotional reactivity to a single
      inhalation of 35% CO(2)-enriched air before deployment significantly potentiated
      the effects of war-zone stressors on the subsequent development of PTSD symptoms
      and general anxiety/stress symptoms but not on the development of depression,
      even after accounting for the effects of trait anxiety and the presence of past
      or current Axis I mental disorders. CONCLUSION: Soldiers' emotional reactivity to
      a 35% CO(2) challenge may serve as a vulnerability factor for increasing
      soldiers' risk for PTSD and general anxiety/stress symptoms in response to war
      zone stressors.

PMID- 23117636
TI  - Childhood adversities and first onset of psychiatric disorders in a national
      sample of US adolescents.
AB  - CONTEXT: Although childhood adversities (CAs) are known to be highly co
      occurring, most research examines their associations with psychiatric disorders
      one at a time. However, recent evidence from adult studies suggests that the
      associations of multiple CAs with psychiatric disorders are nonadditive, arguing
      for the importance of multivariate analysis of multiple CAs. To our knowledge, no
      attempt has been made to perform a similar kind of analysis among children or
      adolescents. OBJECTIVE: To examine the multivariate associations of 12 CAs with
      first onset of psychiatric disorders in a national sample of US adolescents.
      DESIGN: A US national survey of adolescents (age range, 13-17 years) assessing
      DSM-IV anxiety, mood, behavior, and substance use disorders and CAs. The CAs
      include parental loss (death, divorce, and other separations), maltreatment
      (neglect and physical, sexual, and emotional abuse), and parental maladjustment
      (violence, criminality, substance abuse, and psychopathology), as well as
      economic adversity. SETTING: Dual-frame household-school samples. PARTICIPANTS:
      In total, 6483 adolescent-parent pairs. MAIN OUTCOME MEASURES: Lifetime DSM-IV
      disorders assessed using the World Health Organization Composite International
      Diagnostic Interview. RESULTS: Overall, exposure to at least 1 CA was reported by
      58.3% of adolescents, among whom 59.7% reported multiple CAs. The CAs reflecting
      maladaptive family functioning were more strongly associated than other CAs with
      the onset of psychiatric disorders. The best-fitting model included terms for the
      type and number of CAs and distinguished between maladaptive family functioning
      and other CAs. The CAs predicted behavior disorders most strongly and fear
      disorders least strongly. The joint associations of multiple CAs were
      subadditive. The population-attributable risk proportions across DSM-IV disorder
      classes ranged from 15.7% for fear disorders to 40.7% for behavior disorders. The
      CAs were associated with 28.2% of all onsets of psychiatric disorders.
      CONCLUSIONS: Childhood adversities are common, highly co-occurring, and strongly
      associated with the onset of psychiatric disorders among US adolescents. The
      subadditive multivariate associations of CAs with the onset of psychiatric
      disorders have implications for targeting interventions to reduce exposure to CAs
      and to mitigate the harmful effects of CAs to improve population mental health.

PMID- 23117639
TI  - Epidemiologic evidence concerning the bereavement exclusion in major depression.

PMID- 23117641
TI  - Conflicts of interest.

PMID- 23117643
TI  - Does the adult stroma contain stem cells?
AB  - It is well accepted that adult mesenchymal stromal cells (MSCs) comprise
      subpopulations of cells sharing common phenotypical and functional properties.
      However, there is emerging evidence that MSC subpopulations may also feature
      distinct characteristics. This chapter focuses on MSC subpopulations reflecting
      their possible stem cell properties relative to defined pluripotent stem cells
      (PSCs) such as embryonic stem cells (ESCs) or induced pluripotent stem cells
      (iPSCs). This attempt at an ontogenetic reflection on MSCs can be useful for both
      basic and translational research in the field.

PMID- 23117638
TI  - Amygdala volume changes in posttraumatic stress disorder in a large case
      controlled veterans group.
AB  - CONTEXT: Smaller hippocampal volumes are well established in posttraumatic stress
      disorder (PTSD), but the relatively few studies of amygdala volume in PTSD have
      produced equivocal results. OBJECTIVE: To assess a large cohort of recent
      military veterans with PTSD and trauma-exposed control subjects, with sufficient
      power to perform a definitive assessment of the effect of PTSD on volumetric
      changes in the amygdala and hippocampus and of the contribution of illness
      duration, trauma load, and depressive symptoms. DESIGN: Case-controlled design
      with structural magnetic resonance imaging and clinical diagnostic assessments.
      We controlled statistically for the important potential confounds of alcohol use,
      depression, and medication use. SETTING: Durham Veterans Affairs Medical Center,
      which is located in proximity to major military bases. PATIENTS: Ambulatory
      patients (n = 200) recruited from a registry of military service members and
      veterans serving after September 11, 2001, including a group with current PTSD (n
      = 99) and a trauma-exposed comparison group without PTSD (n = 101). MAIN OUTCOME
      MEASURE: Amygdala and hippocampal volumes computed from automated segmentation of
      high-resolution structural 3-T magnetic resonance imaging. RESULTS: Smaller
      volume was demonstrated in the PTSD group compared with the non-PTSD group for
      the left amygdala (P = .002), right amygdala (P = .01), and left hippocampus (P =
      .02) but not for the right hippocampus (P = .25). Amygdala volumes were not
      associated with PTSD chronicity, trauma load, or severity of depressive symptoms.
      CONCLUSIONS: These results provide clear evidence of an association between a
      smaller amygdala volume and PTSD. The lack of correlation between trauma load or
      illness chronicity and amygdala volume suggests that a smaller amygdala
      represents a vulnerability to developing PTSD or the lack of a dose-response
      relationship with amygdala volume. Our results may trigger a renewed impetus for
      investigating structural differences in the amygdala, its genetic determinants,
      its environmental modulators, and the possibility that it reflects an intrinsic
      vulnerability to PTSD.

PMID- 23117644
TI  - Sources of mesenchymal stem cells: current and future clinical use.
AB  - : 

PMID- 23117645
TI  - [Introduction].

PMID- 23117646
TI  - [New advances in anticoagulation: is it time to forget about heparin and vitamin
      K antagonists? Yes].
AB  - For the last 60 years, heparin and vitamin K antagonists have been the
      cornerstone of anticoagulation. Nowadays, the new anticoagulants, such as
      dabigatran, rivaroxaban and apixaban, show potential advantages over classical
      treatments. These agents inhibit specific coagulation factors and are
      administered orally at fixed doses. Furthermore, heparin and vitamin K
      antagonists have a fast onset of action, short-duration and predictable
      therapeutic effects. No interactions with foods have been described, although
      some drug-drug interactions have been reported. At the moment, no antidotes are
      available. However, due to the short half-life of these agents, antidotes are
      less essential. The new anticoagulants are at least as effective and safe as
      traditional treatments in the prevention of venous thromboembolism after
      orthopedic surgery, as well as in the prevention of stroke and systemic embolism
      in non-valvular atrial fibrillation. Dabigatran and rivaroxaban have also been
      shown to be effective in the treatment of acute venous thromboembolism. Due to
      their properties, these drugs could gradually replace heparin and especially
      vitamin K antagonists. Hopefully, many of our patients will be able to
      discontinue classical anticoagulant treatment and others will never begin it.

PMID- 23117647
TI  - [New advances in anticoagulation: is it time to forget about heparin and vitamin
      K antagonists? No].
AB  - The boost given to the new anticoagulants by the results of clinical trials is
      beginning to jeopardize the hegemony of coumadin and heparin therapy, the
      cornerstone of anticoagulation in the last 50 years. The safety and effectiveness
      of this new drug family with respect to warfarin and low-molecular weight heparin
      in the different facets of anticoagulation has been demonstrated, both in
      prophylaxis (total hip and knee replacement) and in treatment (atrial
      fibrillation and venous thromboembolic disease). These agents seem to offer
      superior convenience compared with their predecessors, although it is not clear
      whether this translates into greater treatment adherence when the data are
      analyzed in depth. Another drawback of these agents is their price, a
      consideration of major importance in the last few years, and which would only be
      offset by savings in the cost of the routine blood monitoring required for
      coumadin agents, available in hospitals. Finally, the populations excluded from
      the clinical trials should not be forgotten, as they are the last obstacle to be
      overcome and the basis for justifying the maintenance of heparin or coumadin
      therapy, depending on the case. The present article provides a more detailed
      analysis of these arguments, which serve as the basis for a reflection on the
      early retirement of classical anticoagulants.

PMID- 23117648
TI  - Assessment of proprioceptive exercises in the treatment of rotator cuff disorders
      in nursing professionals: a randomized controlled clinical trial.
AB  - BACKGROUND: Shoulder pain in nursing professionals may lead to limitations in
      occupational and daily activities and consequently interfere with quality of
      life. OBJECTIVE: To compare the effects of two physical therapy programs which
      differed in the proprioceptive exercises used on the nursing professionals with
      rotator cuff disorder, according to quality of life, work satisfaction
      indicators, and pain intensity. METHOD: This study was an experimental,
      randomized, prospective, comparative trial with quantitative data analysis. The
      data sampling was carried out between the months of June 2010 and July 2011 by
      means of a questionnaire containing socio-demographic and professional
      information, the Western Ontario Rotator Cuff Index (WORC), the Occupational
      Stress Indicator (OSI), and the Visual Numeric Scale (VNS). Based on
      randomization, subjects were divided into two groups. Group 1 (control) was
      submitted to stretching and strengthening exercises and cryotherapy. Group 2
      (experimental) was treated with the same protocol as the control group, with the
      addition of proprioception exercises. The data was analyzed by means of the
      Statistical Package for the Social Science version 16.0 for Windows. RESULTS:
      After physical therapy intervention, significant reduction in pain levels
      occurred in both groups, with a significant improvement in quality of life for
      Group 2. No changes were observed in the work satisfaction indicators after the
      two types of physical therapy interventions. CONCLUSIONS: The proprioceptive
      exercises were important in the treatment of musculoskeletal disorders, however
      the results did not allow us to determine which treatment was the most effective
      as there was no significant difference between groups.

PMID- 23117649
TI  - Intra and inter-rater reliability of infrared image analysis of masticatory and
      upper trapezius muscles in women with and without temporomandibular disorder.
AB  - BACKGROUND: Infrared thermography is an aid tool that can be used to evaluate
      several pathologies given its efficiency in analyzing the distribution of skin
      surface temperature. OBJECTIVES: To propose two forms of infrared image analysis
      of the masticatory and upper trapezius muscles, and to determine the intra and
      inter-rater reliability of both forms of analysis. METHOD: Infrared images of
      masticatory and upper trapezius muscles of 64 female volunteers with and without
      temporomandibular disorder (TMD) were collected. Two raters performed the
      infrared image analysis, which occurred in two ways: temperature measurement of
      the muscle length and in central portion of the muscle. The Intraclass
      Correlation Coefficient (ICC) was used to determine the intra and inter-rater
      reliability. RESULTS: The ICC showed excellent intra and inter-rater values for
      both measurements: temperature measurement of the muscle length (TMD group, intra
      rater, ICC ranged from 0.996 to 0.999, inter-rater, ICC ranged from 0.992 to
      0.999; control group, intra-rater, ICC ranged from 0.993 to 0.998, inter-rater,
      ICC ranged from 0.990 to 0.998), and temperature measurement of the central
      portion of the muscle (TMD group, intra-rater, ICC ranged from 0.981 to 0.998,
      inter-rater, ICC ranged from 0.971 to 0.998; control group, intra-rater, ICC
      ranged from 0.887 to 0.996, inter-rater, ICC ranged from 0.852 to 0.996).
      CONCLUSION: The results indicated that temperature measurements of the
      masticatory and upper trapezius muscles carried out by the analysis of the muscle
      length and central portion yielded excellent intra and inter-rater reliability.

PMID- 23117650
TI  - Slower heart rate and oxygen consumption kinetic responses in the on- and off
      transient during a discontinuous incremental exercise: effects of aging.
AB  - BACKGROUND: The analysis of the kinetic responses of heart rate (HR) and oxygen
      consumption (VO(2)) are an important tool for the evaluation of exercise
      performance and health status. OBJECTIVES: The purpose of this study was to
      investigate the effects of aging on the HR and VO(2) kinetics during the rest
      exercise transition (on-transient) and the exercise-recovery transition (off
      transient), in addition to investigating the influence of exercise intensity
      (mild and moderate) on these variables. METHOD: A total of 14 young (23+/-3
      years) and 14 elderly (70+/-4 years) healthy men performed an incremental
      exercise testing (ramp protocol) on a cycle-ergometer to determine the maximal
      power (MP). Discontinuous exercise testing was initiated at 10% of the MP with
      subsequent increases of 10% until exhaustion. The measurement of HR, ventilatory
      and metabolic variables and blood lactate were obtained at rest and during the
      discontinuous exercise. RESULTS: The lactate threshold was determined in each
      subject and was similar between the groups (30+/-7% of MP in the young group and
      29+/-5% of MP in the elderly group, p>0.05). The HR and VO(2) kinetics (on- and
      off-transient) were slower in the elderly group compared to the young group
      (p<0.05). Additionally, in the young group, the values of HR and VO(2) kinetics
      were higher in the moderate compared to the mild exercise intensity. CONCLUSION:
      We concluded that the elderly group presented with slower HR and VO(2) kinetics
      in relation to the young group for both on- and off-transients of the dynamic
      exercise. Moreover, in the young group, the kinetic responses were slower in the
      moderate intensity in relation to the mild intensity.

PMID- 23117651
TI  - Physical activity in daily life in physically independent elderly participating
      in community-based exercise program.
AB  - BACKGROUND: It is unclear whether participation in exercise programs specifically
      developed for elderly translates into a more active lifestyle. OBJECTIVES: To
      compare the objectively measured level of physical activity in daily life (PADL)
      between physically independent elderly who participate or do not participate in
      community-based exercise programs; and to evaluate which factors are associated
      with the higher level of PADL in these subjects. METHOD: 134 elderly participants
      in community-based exercise programs (PG) and 104 non-participants (NPG) had
      their level of PADL measured using pedometers during 7 days. OTHER MEASUREMENTS:
      6-minute walking test (6MWT), incremental shuttle walking test (ISWT), muscle
      strength, flexibility and balance. RESULTS: The PG had higher 1-week mean daily
      step count than NPG (8314 [IQR 5971-10060] vs. 6250 [IQR 4346-8207] steps/day,
      p<0.0001), as well as higher step count in any day of the week. There was a
      higher proportion of physically active subjects (>8000 steps/day) in PG than in
      NPG (37% vs. 16%, respectively; p<0.001), as well as the proportion of sedentary
      subjects (<5000 steps/day) (14% vs. 33%, respectively; p<0.001). Participation in
      exercise programs, 6MWT and ISWT explained a higher daily steps count (model
      r(2)=0.56, p<0.0001). CONCLUSIONS: In physically independent elderly, a higher
      level of physical activity in daily life occurs in those who participate in
      community-based exercise programs, regardless of the weekday and including non
      program days. Participation of elderly in community-based exercise programs
      should be more systematically available and encouraged due to its close link to
      higher activity levels and better exercise capacity.

PMID- 23117652
TI  - Do women with migraine have higher prevalence of temporomandibular disorders?
AB  - OBJECTIVES: The aim of this study was to assess the prevalence of
      Temporomandibular Disorders (TMD), using the Research Diagnostic Criteria for TMD
      (RDC/TMD) in women with episodic and chronic migraine (M and CM), as well as in
      asymptomatic women. METHOD: Sample consisted of 61 women, being 38 with M and 23
      with CM, identified from a headache outpatient center; we also investigated 30
      women without headaches for at least 3 months (women without headache group -
      WHG). Assessment of TMD was conducted by a physical therapist who was blind to
      the headache status. RESULTS: The prevalence of TMD, assessed through the RDC,
      was 33.3% in the WHG, 86.8% in the M group and 91.3% of the CM group. Differences
      were significant when comparing M and CM groups with WHG (p<0.001), but not when
      comparing M and CM (p>0.05) as well as higher risk for TMD [odds ratio (OR)=3.15,
      95% confidence interval (CI) 1.73-5.71 and OR=3.97, 95%CI 1.76-8.94]. CONCLUSION:
      Women with migraine are more likely to have muscular and articular TMD,
      suggesting that both disorders might be clinically associated, which demonstrate
      the importance of physical therapy assessment in the multidisciplinary team.

PMID- 23117653
TI  - Prediction of active sites of enzymes by maximum relevance minimum redundancy
      (mRMR) feature selection.
AB  - Identification of catalytic residues plays a key role in understanding how
      enzymes work. Although numerous computational methods have been developed to
      predict catalytic residues and active sites, the prediction accuracy remains
      relatively low with high false positives. In this work, we developed a novel
      predictor based on the Random Forest algorithm (RF) aided by the maximum
      relevance minimum redundancy (mRMR) method and incremental feature selection
      (IFS). We incorporated features of physicochemical/biochemical properties,
      sequence conservation, residual disorder, secondary structure and solvent
      accessibility to predict active sites of enzymes and achieved an overall accuracy
      of 0.885687 and MCC of 0.689226 on an independent test dataset. Feature analysis
      showed that every category of the features except disorder contributed to the
      identification of active sites. It was also shown via the site-specific feature
      analysis that the features derived from the active site itself contributed most
      to the active site determination. Our prediction method may become a useful tool
      for identifying the active sites and the key features identified by the paper may
      provide valuable insights into the mechanism of catalysis.

PMID- 23117654
TI  - Comparison of 3 kidney injury multiplex panels in rats.
AB  - Kidney injury biomarkers have been utilized by pharmaceutical companies as a
      means to assess the potential of candidate drugs to induce nephrotoxicity.
      Multiple platforms and assay methods exist, but the comparison of these methods
      has not been described. Millipore's Kidney Toxicity panel, EMD/Novagen's
      Widescreen Kidney Toxicity panel, and Meso Scales Kidney Injury panel were
      selected based on published information. Kidney injury molecule 1, cystatin C,
      clusterin, and osteopontin were the 4 biomarkers common among all kits tested and
      the focus of this study. Rats were treated with a low and high dose of para
      aminophenol, a known nephrotoxicant, and urine samples were collected and
      analyzed on the Bio-Plex 200 or MSD's Sector Imager 6000, according to
      manufacturers specifications. Comparatively, of the 3 kits, Millipore was the
      most consistent in detecting elevations of 3 out of the 4 biomarkers at both dose
      levels and indicated time points.

PMID- 23117656
TI  - Galectin-3 mediates aldosterone-induced vascular fibrosis.
AB  - OBJECTIVE: Aldosterone (Aldo) is involved in arterial stiffness and heart
      failure, but the mechanisms have remained unclear. Galectin-3 (Gal-3), a beta
      galactoside-binding lectin, plays an important role in inflammation, fibrosis,
      and heart failure. We investigated here whether Gal-3 is involved in Aldo-induced
      vascular fibrosis. METHODS AND RESULTS: In rat vascular smooth muscle cells Gal-3
      overexpression enhanced specifically collagen type I synthesis. Moreover Gal-3
      inhibition by modified citrus pectin or small interfering RNA blocked Aldo
      induced collagen type I synthesis. Rats were treated with Aldo-salt combined with
      spironolactone or modified citrus pectin for 3 weeks. Hypertensive Aldo-treated
      rats presented vascular hypertrophy, inflammation, fibrosis, and increased aortic
      Gal-3 expression. Spironolactone or modified citrus pectin treatment reversed all
      the above effects. Wild-type and Gal-3 knock-out mice were treated with Aldo for
      6 hours or 3 weeks. Aldo increased aortic Gal-3 expression, inflammation, and
      collagen type I in wild-type mice at both the short- and the long-term, whereas
      no changes occurred in Gal-3 knock-out mice. CONCLUSIONS: Our data indicate that
      Gal-3 is required for inflammatory and fibrotic responses to Aldo in vascular
      smooth muscle cells in vitro and in vivo, suggesting a key role for Gal-3 in
      vascular fibrosis.

PMID- 23117655
TI  - Molecular mechanisms responsible for the reduced expression of cholesterol
      transporters from macrophages by low-dose endotoxin.
AB  - OBJECTIVE: Atherosclerosis is characterized as a chronic inflammatory condition
      that involves cholesterol deposition in arteries. Together with scavenger
      receptor B1 (SR-B1), the ATP-binding cassette transporters ABCA1 and ABCG1 are
      the major components of macrophage cholesterol efflux. Recent studies have shown
      that low-grade inflammation plays a distinct regulatory role in the expression of
      SR-B1 and ABCA1/ABCG1. However, the mechanisms linking low-grade inflammation and
      cholesterol accumulation are poorly understood. METHODS AND RESULTS: Using
      primary bone-marrow-derived macrophages, we demonstrate that subclinical low-dose
      lipopolysaccharide potently reduces the expression of SR-B1 and ABCA1/ABCG1, as
      well as cholesterol efflux from macrophages through interleukin-1 receptor
      associated kinase 1 and Toll-interacting-protein. Low-dose lipopolysaccharide
      downregulates the nuclear levels of retinoic acid receptor-alpha, leading to
      their reduced binding to the promoters of SR-B1 and ABCA1/ABCG1. We observe that
      glycogen synthase kinase 3beta activation by low-dose lipopolysaccharide through
      interleukin-1 receptor-associated kinase 1 and Toll-interacting-protein is
      responsible for reduced levels of retinoic acid receptor-alpha, and reduced
      expression of SR-B1 and ABCA1/ABCG1. Interleukin-1 receptor-associated kinase M,
      however, counteracts the function of interleukin-1 receptor associated kinase 1.
      CONCLUSIONS: Collectively, our data reveal a novel intracellular network
      regulated by low-dose endotoxemia that disrupts cholesterol efflux from
      macrophages and leads to the pathogenesis of atherosclerosis.

PMID- 23117657
TI  - Arterial and venous endothelia display differential functional fractalkine
      (CX3CL1) expression by angiotensin-II.
AB  - OBJECTIVE: Angiotensin-II (Ang-II) promotes the interaction of mononuclear cells
      with arterioles and neutrophils with postcapillary venules. To investigate the
      mechanisms underlying this dissimilar response, the involvement of fractalkine
      (CX(3)CL1) was explored. METHODS AND RESULTS: Enhanced CX(3)CL1 expression was
      detected in both cremasteric arterioles and postcapillary venules 24 hours after
      Ang-II intrascrotal injection. Arteriolar leukocyte adhesion was the unique
      parameter significantly reduced (83%) in animals lacking CX(3)CL1 receptor
      (CX(3)CR1). Human umbilical arterial and venous endothelial cell stimulation with
      1 MUmol/L Ang-II increased CX(3)CL1 expression, yet neutralization of CX(3)CL1
      activity only significantly inhibited Ang-II-induced mononuclear cell-human
      umbilical arterial endothelial cell interactions (73%) but not with human
      umbilical venous endothelial cells. The use of small interfering RNA revealed the
      involvement of tumor necrosis factor-alpha in Ang-II-induced CX(3)CL1
      upregulation and mononuclear cell arrest. Nox5 knockdown with small interfering
      RNA or pharmacological inhibition of extracellular signal-regulated kinases1/2,
      p38 mitogen-activated protein kinase, and nuclear factor-kappaB also abolished
      these responses. Finally, when human umbilical arterial endothelial cells were
      costimulated with Ang-II, tumor necrosis factor-alpha, and interferon-gamma,
      CX(3)CL1 expression and mononuclear cell adhesiveness were more pronounced than
      when each stimulus was provided alone. CONCLUSIONS: These results suggest that
      Ang-II induces functional CX(3)CL1 expression in arterial but not in venous
      endothelia. Thus, targeting endothelial CX(3)CL1-mononuclear leukocyte CX(3)CR1
      interactions may constitute a new therapeutic strategy in the treatment of Ang-II
      associated cardiovascular diseases.

PMID- 23117658
TI  - Transglutaminase inhibitors attenuate vascular calcification in a preclinical
      model.
AB  - OBJECTIVE: In vitro, transglutaminase-2 (TG2)-mediated activation of the beta
      catenin signaling pathway is central in warfarin-induced calcification,
      warranting inquiry into the importance of this signaling axis as a target for
      preventive therapy of vascular calcification in vivo. METHODS AND RESULTS: The
      adverse effects of warfarin-induced elastocalcinosis in a rat model include
      calcification of the aortic media, loss of the cellular component in the vessel
      wall, and isolated systolic hypertension, associated with accumulation and
      activation of TG2 and activation of beta-catenin signaling. These effects of
      warfarin can be completely reversed by intraperitoneal administration of the TG2
      specific inhibitor KCC-009 or dietary supplementation with the bioflavonoid
      quercetin, known to inhibit beta-catenin signaling. Our study also uncovers a
      previously uncharacterized ability of quercetin to inhibit TG2. Quercetin
      reversed the warfarin-induced increase in systolic pressure, underlying the
      functional consequence of this treatment. Molecular analysis shows that quercetin
      diet stabilizes the phenotype of smooth muscle and prevents its transformation
      into osteoblastic cells. CONCLUSIONS: Inhibition of the TG2/beta-catenin
      signaling axis seems to prevent warfarin-induced elastocalcinosis and to control
      isolated systolic hypertension.

PMID- 23117659
TI  - Heritability of venous biomechanics.
AB  - OBJECTIVE: Altered venous biomechanics may contribute to the pathogenesis of
      venous diseases, and their heritability is less known. METHODS AND RESULTS:
      Seventy-eight monozygotic twin pairs (aged 42.4 +/- 16.8 years) and 24 same-sex
      dizygotic twin pairs (aged 50.5 +/- 16.1 years) were examined. Anteroposterior
      and mediolateral diameters of the common femoral vein were measured by
      ultrasonography. Measurements were made both in supine and in standing body
      positions, with or without controlled forced expiration (Valsalva test). High
      correlation of diameter, capacity, and distensibility values was found between
      twin pairs. The univariate heritability (A), shared (C), and unshared (E)
      environmental effects model has shown 39.3% genetic component of the variance of
      low pressure, 37.9% of high-pressure venous capacity, and 36.4% of maximal
      capacity changes, even after elimination of sex, age, and body weight effects.
      Bivariate Cholesky analysis revealed substantial covariance of inherited body
      weight and venous capacity components (57.0%-81.4%). CONCLUSIONS: Femoral vein
      capacity and elasticity depend ~30% to 40% on genetic factors, and this value in
      the standing body position can reach 50%. A relatively high genetic covariance
      was found between weight and femoral vein capacity and elasticity. Our work might
      yield some new insights into the inheritance of venous diseases that are
      associated with altered venous biomechanics and help elucidate the involved
      genes.

PMID- 23117660
TI  - Transcriptome analysis for Notch3 target genes identifies Grip2 as a novel
      regulator of myogenic response in the cerebrovasculature.
AB  - OBJECTIVE: Notch3 is critically important for the structure and myogenic response
      of distal arteries, particularly of cerebral arteries. However, signaling
      pathways acting downstream of Notch3 remain largely unknown. METHODS AND RESULTS:
      Transcriptome analysis using tail arteries of Notch3-null mice identified a core
      set of 17 novel Notch3-regulated genes confirmed in tail or brain arteries.
      Postnatal deletion of RBP-Jkappa in smooth muscle cells recapitulated the
      structural, functional, and molecular defects of brain arteries induced by Notch3
      deficiency. Transient in vivo blockade of the Notch pathway with gamma-secretase
      inhibitors uncovered, in addition to Notch3, 6 immediate responders, including
      the voltage-gated potassium channel Kv1.5, which opposes to myogenic constriction
      of brain arteries, and the glutamate receptor-interacting protein 2 (Grip2) with
      no previously established role in the cerebrovasculature. We identified a
      vascular smooth muscle cell isoform of Grip2. We showed that Notch3-RBP-Jkappa
      specifically regulates this isoform. Finally, we found that cerebral arteries of
      Grip2 mutant mice, which express an N-terminally truncated Grip2 protein,
      exhibited selective attenuation of pressure-induced contraction. CONCLUSIONS: Our
      data provide insight into how Notch3 signals in the brain arteries, establishing
      the postnatal requirement of smooth muscle RBP-Jkappa in this context. Notch3
      regulated transcriptome provides potential for modulating myogenic response in
      the cerebrovasculature.

PMID- 23117663
TI  - [Concepts in anticoagulant therapy - past, present, and future].
AB  - The understanding of the clotting system emerged in parallel to the development
      of anticoagulants. In contrast to vitamin K-antagonists and heparins that where
      discovered by chance, new anticoagulants have been systematically designed to
      specifically inhibit single clotting factors. Both clotting factors Xa (FXa) and
      thrombin play a crucial role within the new cell-based model of hemostasis. Thus
      it is obvious that FXa and thrombin turned out to be ideal targets for
      anticoagulation. The proof of the concept of selective inhibition of thrombin and
      FXa has been provided by hirudin and fondaparinux, respectively. By now, a whole
      group of new oral anticoagulants has been licensed: the direct FXa-inhibitors
      rivaroxaban, apixaban, and edoxaban as well as the direct thrombin dabigatran
      etexilate. Furthermore, a bundle of FXa- and thrombin-inhibitors that differ from
      the so far licensed products mainly in pharmacokinetics are in an advanced phase
      of development. A further innovative concept of anticoagulation that entered its
      clinical phase of development is the inhibition of factor VIII. Other new
      concepts such as inhibition of initiation of coagulation by blocking factor VIIa,
      inhibition of contact factor XII, or inhibition of factor IX are in an early
      phase of development.

PMID- 23117662
TI  - Heterogeneity of platelet functional alterations in patients with filamin A
      mutations.
AB  - OBJECTIVE: We examined platelet functions in 4 unrelated patients with
      filaminopathy A caused by dominant mutations of the X-linked filamin A (FLNA)
      gene. METHODS AND RESULTS: Patients P1, P2, and P4 exhibited periventricular
      nodular heterotopia, heterozygozity for truncating FLNA mutations, and
      thrombocytopenia (except P2). P3 exhibited isolated thrombocytopenia and
      heterozygozity for a p.Glu1803Lys FLNA mutation. Truncated FLNA was undetectable
      by Western blotting of P1, P2, and P4 platelets, but full-length FLNA was
      detected at 37%, 82%, and 57% of control, respectively. P3 FLNA (p.Glu1803Lys and
      full-length) was assessed at 79%. All patients exhibited a platelet subpopulation
      negative for FLNA. Platelet aggregation, secretion, glycoprotein VI signaling,
      and thrombus growth on collagen were decreased for P1, P3, and P4, but normal for
      P2. For the 2 patients analyzed (P1 and P4), spreading was enhanced and, more
      markedly, in FLNA-negative platelets, suggesting that FLNA negatively regulates
      cytoskeleton reorganization. Platelet adhesion to von Willebrand factor under
      flow correlated with platelet full-length FLNA content: markedly reduced for P1
      and P4 and unchanged for P2. Interestingly, von Willebrand factor flow adhesion
      was increased for P3, consistent with a gain-of-function effect enhancing
      glycoprotein Ib-IX-V/von Willebrand factor interaction. These results are
      consistent with a positive role for FLNA in platelet adhesion under high shear.
      CONCLUSIONS: FLNA mutation heterogeneity correlates with different platelet
      functional impacts and points to opposite regulatory roles of FLNA in spreading
      and flow adhesion under shear.

PMID- 23117661
TI  - Donor and recipient cell surface colony stimulating factor-1 promote neointimal
      formation in transplant-associated arteriosclerosis.
AB  - OBJECTIVE: Transplant-associated arteriosclerosis manifests as progressive
      vascular neointimal expansion throughout the arterial system of allografted solid
      organs, and eventually compromises graft perfusion and function. Allografts
      placed in colony stimulating factor (CSF)-1-deficient osteopetrotic
      (Csf1(op)/Csf1(op)) mice develop very little neointima, a finding attributed to
      impaired recipient macrophage function. We examined how CSF-1 affects neointima
      derived vascular smooth muscle cells, tested the significance of CSF-1 expressed
      in donor tissue, and evaluated the contribution of secreted versus cell surface
      CSF-1 isoforms in transplant-associated arteriosclerosis. METHODS AND RESULTS:
      CSF-1 activated specific signaling pathways to promote migration, survival, and
      proliferation of cultured vascular smooth muscle cells. Tumor necrosis factor
      alpha addition increased CSF-1 and CSF-1 receptor expression, and tumor necrosis
      factor-alpha-driven proliferation was blocked by anti-CSF-1 antibody. In a mouse
      vascular allograft model, lack of recipient or donor CSF-1 impaired neointima
      formation; the latter suggests local CSF-1 function within the allograft.
      Moreover, reconstitution of donor or recipient cell surface CSF-1, without
      secreted CSF-1, restored neointimal formation. CONCLUSIONS: Vascular smooth
      muscle cells activation, including that mediated by tumor necrosis factor-alpha,
      can be driven in an autocrine/juxtacrine manner by CSF-1. These studies provide
      evidence for local function of CSF-1 in neointimal expansion, and identify CSF-1
      signaling in vascular smooth muscle cells, particularly cell surface CSF-1
      signaling, as a target for therapeutic strategies in transplant-associated
      arteriosclerosis.

PMID- 23117664
TI  - [Platelet inhibitors in clinical practice].
AB  - Despite improvements in the treatment of acute coronary syndromes, cardiovascular
      disease remains the leading cause of death in Europe and the United States.
      Antiplatelet agents, such as aspirin and clopidogrel, play an important role in
      the treatment of those patients. Several new alternatives have been tested in
      clinical trails and some of them have been approved for routine treatment of
      patients with ACS in Switzerland and the European Union. The latter include
      Prasugrel (Efient(r)) and Ticagrelor (Brilique(r)). Those substances provide more
      rapid and consistent platelet inhibition but increase the risk of bleeding in
      some patient subgroups. Thus, the main challenge is to tailor treatment for each
      patient by taking into consideration patient characteristics, comorbidities,
      underlying short- and long-term risk factors, ischemic and bleeding risks, and
      expected individual responses to different medications. This ambitious new
      approach will be a challenge for in daily clinical work and may ultimately
      require prioritization among several treatment alternatives. In this article, we
      review the new antiplatelet agents being developed as well as their
      pharmacological characteristics, key interactions and side effects and potential
      clinical indications in subpopulations.

PMID- 23117665
TI  - [Platelet inhibition in clinical practice].
AB  - Evidence for a beneficial effect of antiaggregatory treatment is strong for many
      clinical entities. However, there are controversial situations challenging us in
      daily practice, such as failure of antiaggregatory therapy (case 1), inconclusive
      evidence for the benefit of certain antiaggregatory medications (case 2) or
      increased risk of bleeding in aorto-coronary bypass surgery after irreversible
      antiaggregation (case 3). The phenomenon of aspirin or clopidogrel resistance
      means the occurrence of ischemic complications despite adequate antiaggregation.
      It may be caused by malcompliance, variable bioavailability, drug interactions or
      genetic polymorphisms. For peripheral arterial occlusive disease, a beneficial
      effect of aspirin is questioned by recent studies in contrast to the
      recommendations given in international guidelines. Finally, irreversible
      inhibition of platelet aggregation by GPIIb/IIIa inhibitors given during
      percutaneous coronary intervention can be overcome by transfusion of functional
      platelets to reduce bleeding during subsequent bypass surgery. Further studies
      will help to improve the management of antiaggregatory therapy in such
      challenging clinical situations.

PMID- 23117666
TI  - [New anticoagulants - direct factor Xa-inhibitors].
AB  - The direct oral factor Xa-inhibitors are at present in clinical use as
      antithrombotics, after their efficiency and safety have been proved in clinical
      studies. Three products are actually in the market, rivaroxaban (Xarelto(r))
      apixaban (Eliquis(r)) and edoxaban (Lixiana(r)). Efficacy and safety have been
      tested for rivaroxaban and apixaban in large study programmes with more than
      60'000 patients each. For edoxaban large phase III studies are under way. Based
      on these data rivaroxaban was registered in the EU and CH for primary prophylaxis
      against thrombosis after major orthopaedic surgery, such as hip- and knee-joint
      protheses, for treatment and prophylaxis of deep vein thrombosis and pulmonary
      embolism and for prophylaxis against thromboembolic stroke in patients with
      atrial fibrillation. Apixaban is presently registered in the EU and CH for
      prophylaxis against thrombosis after major orthopaedic surgery, Edoxaban is
      registered only in Japan for the same indication. These products have been shown
      to be non-inferior or superior compared with vitamin K antagonists or low
      molecular weight heparins, they are administered once or twice a day, they do not
      need laboratory monitoring. But they have disadvantages also, they depend on
      renal clearance, they can interact with other medicaments and they lack a
      specific antidote. In total, though, they are considered as a progress for the
      appropriate patients in terms of quality of treatment.

PMID- 23117667
TI  - [New anticoagulants - direct thrombin inhibitors].
AB  - Direct thrombin-inhibitors inactivate not only free but also fibrin-bound
      thrombin. The group of parenteral direct thrombin-inhibitors includes the
      recombinant hirudins lepirudin and desirudin, the synthetic hirudin bivalirudin,
      and the small molecule argatroban. All these compounds do not interact with
      PF4/heparin-antibodies. Therefore, argatroban as well as bivalirudin are
      currently used to treat heparin-induced thrombocytopenia (HIT). The oral direct
      thrombin-inhibitor dabigatran etexilate is already licensed in many countries for
      the treatment of non-valvular atrial fibrillation. Dabigatran etexilate reveals a
      stable and predictable effect that allows a medication without dose adjustment or
      monitoring. The substance shows only few interactions with other drugs but strong
      inhibitors of p-glycoprotein can increase plasma levels of dabigatran
      substantially. After oral intake, the prodrug dabigatran etexilate is cleaved by
      esterase-mediated hydrolyses to the active compound dabigatran. Elimination of
      dabigatran is predominantly renal. Safety and efficacy of dabigatran etexilate
      were tested in an extensive clinical study program. Non-inferiority compared to
      current standard treatments was shown for prophylaxis of venous thromboembolic
      events after total knee and hip replacement, for stroke prevention in atrial
      fibrillation, and for treatment of acute venous thromboembolism. In daily
      practice, Dabigatran etexilate competes against the new direct factor Xa
      inhibitors. In the absence of direct comparative clinical trials, it is not yet
      clear if one class of substances has distinct advantages over the other.

PMID- 23117668
TI  - [Laboratory diagnostic with regard to new anticoagulants - monitoring and
      influence on coagulation tests].
AB  - New oral anticoagulants promise to overcome essential drawbacks of traditional
      substances. They have a predictable therapeutic effect, a wide therapeutic
      window, only limited interaction with food and drugs and can be administered p.o.
      with a fixed dose. On the other hand, knowledge on the laboratory management of
      new anticoagulants is limited. In the present article we discuss possible
      indications and available assays for monitoring of Rivaroxaban, Apixaban and
      Dabigatran. Furthermore, we discuss interpretation of routine coagulation tests
      during therapy with these new drugs.

PMID- 23117669
TI  - [Clinical pharmacological aspects of new oral anticoagulants].
AB  - New oral anticoagulants such as the factor Xa inhibitors rivaroxaban and apixaban
      or the thrombin inhibitor dabigatran lack some of the limitations of the well
      known vitamin K-antagonists. Although routine monitoring is not required, large
      variations in overall exposure can be seen under certain circumstances.
      Dabigatran is primarily eliminated in unchanged form in the urine and dose has to
      be adapted according to renal function. The factor Xa inhibitors are CYP3A4
      substrates and combination with potent CYP3A4-inhibitors is not allowed. In cases
      of bleeding or thromboembolic events under treatment, targeted monitoring of drug
      concentration or anti-FXa- or anti-FIIa-activity may be helpful to identify the
      underlying cause. In contrast to vitamin K antagonists or heparin, no antidotes
      are available for the new anticoagulants and the optimal procedure in cases of
      life-threatening bleeding has not yet been defined. For certain indications such
      as prophylaxis of venous thromboembolism in acutely ill medical patients study
      data are (not yet) available. Concerning localization of bleeding sites the new
      compounds may display a different profile compared to vitamin K-antagonists (less
      intracranial bleedings). Experience with long-term use (> 5 years) is limited.
      Therefore careful clinical monitoring of patients considering co-medication and
      co-morbidity is necessary to allow safe therapy with the new oral anticoagulants.

PMID- 23117670
TI  - Interactions between visual and motor areas during the recognition of plausible
      actions as revealed by magnetoencephalography.
AB  - Several studies have shown activation of the mirror neuron system (MNS),
      comprising the temporal, posterior parietal, and sensorimotor areas when
      observing plausible actions, but far less is known on how these cortical areas
      interact during the recognition of a plausible action. Here, we recorded neural
      activity with magnetoencephalography while subjects viewed point-light displays
      of biologically plausible and scrambled versions of actions. We were interested
      in modulations of oscillatory activity and, specifically, in coupling of
      oscillatory activity between visual and motor areas. Both plausible and scrambled
      actions elicited modulations of theta (5-7 Hz), alpha (7-13 Hz), beta (13-35 Hz),
      and gamma (55-100 Hz) power within visual and motor areas. When comparing between
      the two actions, we observed sequential and spatially distinct increases of gamma
      (~65 Hz), beta (~25 Hz), and alpha (~11 Hz) power between 0.5 and 1.3 s in
      parieto-occipital, sensorimotor, and left temporal areas. In addition,
      significant clusters of gamma (~65 Hz) and alpha/beta (~15 Hz) power decrease
      were observed in right temporal and parieto-occipital areas between 1.3 and 2.0
      s. We found beta-power in sensorimotor areas to be positively correlated on a
      trial-by-trial basis with parieto-occipital gamma and left temporal alpha-power
      for the plausible but not for the scrambled condition. These results provide new
      insights in the neuronal oscillatory activity of the areas involved in the
      recognition of plausible action movements and their interaction. The power
      correlations between specific areas underscore the importance of interactions
      between visual and motor areas of the MNS during the recognition of a plausible
      action.

PMID- 23117671
TI  - Flashed stimulation produces strong simultaneous brightness and color contrast.
AB  - Simultaneous brightness contrast and simultaneous color contrast are classical
      illusions that demonstrate how our perception can be altered by spatial context;
      a central gray region appears to have brightness and color that are complementary
      to those of a surrounding region. Previous studies have suggested the involvement
      of a sluggish process in these illusions. On the other hand, a different, fast
      mechanism has recently been postulated to operate in simultaneous contrast when
      the stimulus is presented only briefly. Here, we show that in briefly flashed
      stimuli, not only the simultaneous brightness contrast but also the simultaneous
      color contrast is perceived with greatly enhanced illusion strength. In
      simultaneous brightness contrast, inserting a spatial gap between the center and
      surround weakened the illusion only when the stimulus was flashed. In
      simultaneous color contrast, the gap weakened the illusion irrespective of
      stimulus duration. Both brightness contrast and color contrast effects steeply
      decayed with duration. The present study suggests the existence of a fast
      responding process for estimating brightness/color primarily based on local
      difference in luminance/color along the edge between the center and surround. We
      argue that the sluggishness of simultaneous contrast demonstrated by previous
      studies originated from a sluggish process after local and fast spatial
      interactions.

PMID- 23117672
TI  - da Vinci decoded: does da Vinci stereopsis rely on disparity?
AB  - In conventional stereopsis, the depth between two objects is computed based on
      the retinal disparity in the position of matching points in the two eyes. When an
      object is occluded by another object in the scene, so that it is visible only in
      one eye, its retinal disparity cannot be computed. Nakayama and Shimojo (1990)
      found that a precept of quantitative depth between the two objects could still be
      established for such stimuli and proposed that this precept is based on the
      constraints imposed by occlusion geometry. They named this and other occlusion
      based depth phenomena "da Vinci stereopsis." Subsequent research found
      quantitative depth based on occlusion geometry in several other classes of
      stimuli grouped under the term da Vinci stereopsis. However, Nakayama and
      Shimojo's findings were later brought into question by Gillam, Cook, and
      Blackburn (2003), who suggested that quantitative depth in their stimuli was
      perceived based on conventional disparity. In order to understand whether da
      Vinci stereopsis relies on one type of mechanism or whether its function is
      stimulus dependent we examine the nature and source of depth in the class of
      stimuli used by Nakayama and Shimojo (1990). We use three different
      psychophysical and computational methods to show that the most likely source for
      depth in these stimuli is occlusion geometry. Based on these experiments and
      previous data we discuss the potential mechanisms responsible for processing
      depth from monocular features in da Vinci stereopsis.

PMID- 23117673
TI  - Molecular and biochemical characterization of a new alkaline active multidomain
      xylanase from alkaline wastewater sludge.
AB  - A xylanase gene, xyn-b39, coding for a multidomain glycoside hydrolase (GH)
      family 10 protein was cloned from the genomic DNA of the alkaline wastewater
      sludge of a paper mill. Its deduced amino acid sequence of 1,481 residues
      included two carbohydrate-binding modules (CBM) of family CBM_4_9, one catalytic
      domain of GH 10, one family 9 CBM and three S-layer homology (SLH) domains. xyn
      b39 was expressed heterologously in Escherichia coli, and the recombinant enzyme
      was purified and characterized. Xyn-b39 exhibited maximum activity at pH 7.0 and
      60  degrees C, and remained highly active under alkaline conditions (more than 80
      % activity at pH 9.0 and 40 % activity at pH 10.0). The enzyme was thermostable
      at 55  degrees C, retaining more than 90 % of the initial activity after 2 h pre
      incubation. Xyn-b39 had wide substrate specificity and hydrolyzed soluble
      substrates (birchwood xylan, beechwood xylan, oat spelt xylan, wheat
      arabinoxylan) and insoluble substrates (oat spelt xylan and wheat arabinoxylan).
      Hydrolysis product analysis indicated that Xyn-b39 was an endo-type xylanase. The
      K (m) and V (max) values of Xyn-b39 for birchwood xylan were 1.01 mg/mL and 73.53
      U/min/mg, respectively. At the charge of 10 U/g reed pulp for 1 h, Xyn-b39
      significantly reduced the Kappa number (P < 0.05) with low consumption of
      chlorine dioxide alone.

PMID- 23117674
TI  - Control of postharvest soft rot caused by Erwinia carotovora of vegetables by a
      strain of Bacillus amyloliquefaciens and its potential modes of action.
AB  - Erwinia carotovora subsp. carotovora (Ecc), the causal agent of bacterial soft
      rot, is one of the destructive pathogens of postharvest vegetables. In this
      study, a bacterial isolate (BGP20) from the vegetable farm soil showed strong
      antagonistic activity against Ecc in vitro, and its twofold cell-free culture
      filtrate showed excellent biocontrol effect in controlling the postharvest
      bacterial soft rot of potatoes at 25  degrees C. The anti-Ecc metabolites
      produced by the isolate BGP20 had a high resistance to high temperature, UV-light
      and protease K. Based on the colonial morphology, cellular morphology,
      sporulation, and partial nucleotide sequences of 16S rRNA and gyrB gene, the
      isolate BGP20 was identified as Bacillus amyloliquefaciens subsp. plantarum.
      Further in vivo assays showed that the BGP20 cell culture was more effective in
      controlling the postharvest bacterial soft rot of green peppers and Chinese
      cabbages than its twofold cell-free culture filtrate. In contrast, the biocontrol
      effect and safety of the BGP20 cell culture were very poor on potatoes. In the
      wounds of potatoes treated with both the antagonist BGP20 and the pathogen Ecc,
      the viable count of Ecc was 31,746 times that of BGP20 at 48 h of incubation at
      25  degrees C. But in the wounds of green peppers, the viable count of BGP20
      increased 182.3 times within 48 h, and that of Ecc increased only 51.3 %. In
      addition, the treatment with both BGP20 and Ecc induced higher activity of
      phenylalanine ammonia-lyase (PAL) than others in potatoes. But the same treatment
      did not induce an increase of PAL activity in green peppers. In conclusion, the
      present study demonstrated that the isolate BGP20 is a promising candidate in
      biological control of postharvest bacterial soft rot of vegetables, but its main
      mode of action is different among various vegetables.

PMID- 23117675
TI  - Ethanol production by Saccharomyces cerevisiae using lignocellulosic hydrolysate
      from Chrysanthemum waste degradation.
AB  - Ethanol production derived from Saccharomyces cerevisiae fermentation of a
      hydrolysate from floriculture waste degradation was studied. The hydrolysate was
      produced from Chrysanthemum (Dendranthema grandiflora) waste degradation by
      Pleurotus ostreatus and characterized to determine the presence of compounds that
      may inhibit fermentation. The products of hydrolysis confirmed by HPLC were
      cellobiose, glucose, xylose and mannose. The hydrolysate was fermented by S.
      cerevisiae, and concentrations of biomass, ethanol, and glucose were determined
      as a function of time. Results were compared to YGC modified medium (yeast
      extract, glucose and chloramphenicol) fermentation. Ethanol yield was 0.45 g g(
      1), 88 % of the maximal theoretical value. Crysanthemum waste hydrolysate was
      suitable for ethanol production, containing glucose and mannose with adequate
      nutrients for S. cerevisiae fermentation and low fermentation inhibitor levels.

PMID- 23117676
TI  - Biodegradation of the herbicide propanil, and its 3,4-dichloroaniline by-product
      in a continuously operated biofilm reactor.
AB  - The persistence of propanil in soil and aquatic environments along with the
      possible accumulation of toxic degradation products, such as chloroanilines, is
      of environmental concern. In this work, a continuous small-scale bioprocess to
      degrade the herbicide propanil, its main catabolic by-product, 3,4
      dichloroaniline (3,4-DCA), and the herbicide adjuvants is carried out. A
      microbial consortium, constituted by nine bacterial genera, was selected. The
      isolated strains, identified by amplification and sequencing of their 16S rDNA,
      were: Acidovorax sp., Luteibacter (rhizovicinus), Xanthomonas sp., Flavobacterium
      sp., Variovorax sp., Acinetobacter (calcoaceticus), Pseudomonas sp., Rhodococcus
      sp., and Kocuria sp. The ability of the microbial consortium to degrade the
      herbicide was evaluated in a biofilm reactor at propanil loading rates ranging
      from 1.9 to 36.8 mg L(-1) h(-1). Complete removal of propanil, 3,4-DCA, chemical
      oxygen demand and total organic carbon was obtained at propanil loading rates up
      to 24.9 mg L(-1) h(-1). At higher loading rates, the removal efficiencies
      decayed. Four of the identified strains could grow individually in propanil, and
      3,4-DCA: Pseudomonas sp., Acinetobacter calcoaceticus, Rhodococcus sp., and
      Xanthomonas sp. The Kokuria strain grew on 3,4-DCA, but not on propanil. The
      first three bacteria have been related to biodegradation of phenyl urea
      herbicides or chlorinated anilines. Although some strains of the genera
      Xanthomonas and Kocuria have a role in the biodegradation of several xenobiotic
      compounds, as far as we know, there are no reports about degradation of propanil
      by Xanthomonas or 3,4-DCA by Kocuria species.

PMID- 23117678
TI  - Right ventricular failure: a continuing problem in the new era of left
      ventricular assist device therapy.

PMID- 23117677
TI  - Evaluation of probiotic properties of Lactobacillus plantarum strains isolated
      from Chinese sauerkraut.
AB  - Lactobacillus plantarum strains isolated and identified from naturally-fermented
      Chinese sauerkraut were examined in vitro for potential probiotic properties and
      in vivo for cholesterol-lowering effect in mice. Among 7 isolated L. plantarum
      strains, strains S2-5 and S4-1 were found to possess desirable probiotic
      properties including ability to survive at pH 2.0 for 60 min, tolerate pancreatin
      and bile salts, adhere to Caco-2 cells, produce high beta-galactosidase activity
      and antimicrobial activity against Escherichia coli O157 and Shigella flexneri
      CMCC(B). In addition, strains S2-5 and S4-1 were susceptible to several
      antibiotics, and capable of reducing cholesterol level in MRS medium by
      assimilation of cholesterol at 20.39 and 22.28 MUg ml(-1), respectively. The in
      vivo study with L. plantarum S4-1 showed that feeding with fermented milk
      containing this strain was able to effectively reduce serum cholesterol level in
      mice, demonstrating its potential as an excellent probiotic candidate for
      applications in functional products.

PMID- 23117679
TI  - Coronary arterial remodeling and out-stent plaque change after drug-eluting stent
      implantation--comparison between zotarolimus-eluting stents and paclitaxel
      eluting stents.
AB  - BACKGROUND: Out-stent plaque characteristics and eosinophilic inflammatory
      response, which correlates with positive remodeling after first-generation drug
      eluting stent implantation, may be associated with late restenosis and very late
      stent thrombosis. The differences of out-stent plaque characteristics were
      compared between paclitaxel-eluting stents (PES) and zotarolimus-eluting stents
      (ZES), using integrated backscatter-intravascular ultrasound (IB-IVUS). METHODS
      AND RESULTS: Of 78 patients enrolled, 25 receiving PES and 25 receiving ZES had
      adequate IVUS assessment. Volumetric IVUS analysis was performed after stenting
      and at 8-month follow-up. Out-stent plaque change in the stented segment was
      compared on IB-IVUS. The relationship between systemic inflammatory response and
      out-stent plaque change was evaluated. In PES, vessel volume significantly
      increased (365-389 mm(3), P<0.0001), whereas it did not change in ZES (315-314
      mm(3), P=0.81). In culprit lesions at baseline in PES, fibrous plaque tended to
      increase (3.1-3.6mm(2), P=0.051) and lipid plaque significantly increased (4.3
      5.1mm(2), P=0.02), whereas in ZES the fibrous plaque significantly increased (2.9
      4.0mm(2), P<0.0001) but lipid plaque significantly decreased (5.1-3.6mm(2),
      P<0.0001). Systemic eosinophil increase was significantly correlated with
      positive remodeling and out-stent lipid plaque increase. CONCLUSIONS: Chronic out
      stent plaque change in ZES consisted of less positive remodeling and more
      favorable effects on out-stent plaque characteristics than PES. Systemic
      eosinophil change might be a marker of out-stent lipid plaque change.

PMID- 23117680
TI  - Perineal radical prostatectomy in the minimally invasive era.
AB  - Radical prostatectomy is currently the standard of care for localized prostate
      cancer. In the last decade, the minimally invasive surgery, especially the
      robotic surgery has  been growing and open techniques are less frequent
      performed. A non-systematic review of the literature is performed, highlighting
      the current situation of the perineal radical prostatectomy in the minimally
      invasive era, its  indications, and functional and oncological outcomes. Radical
      perineal prostatectomy, when compared with other surgical approaches, still
      experience favorable outcomes. Urologist might be abandoning an underused
      surgical  approach.

PMID- 23117681
TI  - Implementing an action protocol on prostatic disease in primary care and impact
      on referrals to urology.
AB  - OBJECTIVES: To determine the impact of implementing a joint action protocol on
      prostatic disease on the referrals to Urology from Primary Care in a health care
      area. METHODS: We drafted a protocol for managing patients consulting for
      clinical signs and symptoms associated to benign prostatic hyperplasia (BPH) and
      to test PSA in asymptomatic males. At the same time, three e-mail addresses were
      opened for consultations  generated from Primary  Care, and joint sessions were
      carried out in the primary health care centers. We measured the impact of the
      protocol by assessing the adequacy of prostatic disease referrals to Urology, as
      well as by determining the course of the total number of referrals in three
      peripheral specialized health care centers (PSHCC). RESULTS: From January 2011, a
      better compliance to the referrals to Urology protocol for prostatic disease has
      been produced, going from 47% (assessment prior to  implementing the protocol) to
      64%. These results are especially good when we consider referrals associated to
      PSA, which went from a compliance of 33% to 84%. Regarding the course of the
      referrals to Urology, the referral rate (referrals per 1000 inhabitants) has
      decreased by 15% (from 13,8 to 11,7). CONCLUSIONS: The collaboration between
      Urology and Primary health care, by means of implementing joint protocols, and
      also by establishing new communication channels  (e-mail, joint sessions),
      achieves a better adequacy of patients referred for prostatic disease, as well as
      a reduction in the total number of referrals.

PMID- 23117682
TI  - Transdermal iontophoresis with verapamil and dexamethasone in the acute phase of
      peyronie's disease. Our experience.
AB  - OBJECTIVES: To evaluate the treatment of Peyronie's disease (PD) with verapamil
      and dexamethasone iontophoresis. METHODS: Twenty nine patients with PD were
      treated by means of a Miniphysionize" dispositive 3 sessions a week during 4
      consecutive weeks.  5mL of a combination of  verapamil(10mg.) and dexamethasone
      (4mg.) were transdermally administered with a 2.5 mA current during 20 min. The
      aim  is to evaluate treatment  efficacy in  correcting penile curvature (Kelami
      test), plaque size (penis ultrasound (US)) improvement of pain and,  other
      parameters like erectile function (EF), intercourse capacity or adverse effects
      of the treatment, which were evaluated with  questionnaires. RESULTS: All
      patients completed the treatment protocol (12 sessions) and a total number of 348
      sessions of iontophoresis were performed.  After treatment,  3 patients (10.7%)
      continued with pain, but it disappeared in 25 of them (89.3%). A decrease of the
      size of the  plaque was observed in 13  patients (44.8%),  even disappearance in
      4 patients (13.8%). No patient had curvature decrease after treatment. However,
      EF (IIEF score)  and ability for intercourse  improved in 3 (10.3%)  and 4
      patients (13.8%) respectively. CONCLUSION: Verapamil and dexamethasone
      iontophoresis is a safe and reliable treatment resolving painful erections in the
      acute phase of PD. However its efficacy in solving  penile curvature and erectile
      dysfunction (ED) is more limited.

PMID- 23117683
TI  - Use of a barbed suture for the urethro-vesical anastomosis during the learning
      curve of the endoscopic extraperitoneal radical prostatectomy.
AB  - OBJECTIVES: The performance of the urethrovesical anastomosis is one of the most
      difficult steps in urologic laparoscopy. Many different techniques have been
      developed  to improve this step and, recently, new sutures such as the V-loc (R)
      barbed system have been created. In the present study we analyze the usefulness
      of  this suture for  diminishing the time employed for the anastomosis suture
      during the learning curve of laparoscopic radical prostatectomy. METHOD: We
      performed a prospective comparative study between two groups. The first group
      included the first 50 cases of a novel surgeon using this barbed suture, and we
      compared these procedures with 50 consecutives cases of an experienced surgeon.
      We compared  preoperative parameters, surgical and suturing times, as well as
      drain and catheter duration, and hospital stay. RESULTS: We did not find
      statistically significant differences in any pre or postoperative parameters
      between both groups. Although surgical time was lower in the control  group this
      difference was not statistically significant. The time used to perform the suture
      was lower in the study group, and we found significant differences between both 
      groups. Neither drain nor bladder catheter times were different between groups.
      CONCLUSIONS: In the absence of prospective randomized trials comparing barbed or
      not barbed running sutures, our study shows that the use of the V-loc(r) system 
      improves the times needed for the urethrovesical anastomosis during the learning
      curve of laparoscopic radical prostatectomy.

PMID- 23117684
TI  - Ureteral inverted papilloma: laparoscopic distal ureterectomy and boari flap.
AB  - OBJECTIVE: To report a case of ureteral inverted papilloma (IP) with laparoscopic
      resolution. METHODS: We report the case of a 30-year-old male patient who
      consulted for asymptomatic hematuria with the radiological finding of a  filling
      defect at the distal right ureter. Ureteroscopy biopsy was not diagnostic, so
      laparoscopic ureterectomy with a Boari flap technique was performed.  The
      pathology report showed a ureteral inverted papilloma. CONCLUSION: Laparoscopic
      ureteral replacement by Boari flap is a safe surgical alternative for defects in
      the distal ureter with the advantages of  a minimally invasive procedure.

PMID- 23117685
TI  - Discontinuous intrabdominal splenogonadal fusion with germ cell tumor. Excision
      with robotic assistence. Adult case report.
AB  - OBJECTIVE: Present the case of a patient with a discontinuous intrabdominal
      splenogonadal fusion with an associated germ cell tumor. METHODS: A case of a man
      of 29 years with bilateral cryptorchidism and left intra-abdominal discontinuous
      splenogonadal fusion associated with seminoma as an accidental  finding in the
      context of a robotic pyeloplasty due to ipsilateral ureteropelvic junction
      stenosis. RESULTS: The total operative time was 80 minutes (atrophic gonad
      removal and pyeloplasty by the Anderson-Hynes technique) with an estimated blood
      loss less  than 100 cc. The hospitalization time was less than 36 hrs. The
      pathology and immunohistochemical report was compatible with intratubular germ
      cell neoplasia (seminoma). CONCLUSION: The splenogonadal fusion is an uncommon
      pathology. While a high clinical suspicion may avoid unnecessary orchiectomy in
      young patients, its association with  disorders such as cryptorchidism should
      make us suspect the possible presence of a concomitant germ cell neoplasia.

PMID- 23117686
TI  - Calyceal fistula: a problematic, but treatable, complication of renal
      transplantation.
AB  - OBJECTIVE: Calyceal fistula is a rare complication of renal transplantation that
      may lead to graft loss. This article reports a case of functional recuperation of
      a  graft that seemed condemned to failure. METHODS: 31 year old male patient,
      submitted to living donor renal transplant, in which was necessary to ligate a
      superior polar artery found during donor nephrectomy,  due to its short length.
      This resulted in development of a calyceal fistula, unsolved with conservative
      treatment by percutaneous drainage. A new surgical intervention revealed a large
      upper pole area of necrotic tissue, corresponding to the obliterated artery
      irrigation zone. RESULTS: Debridement and calyceal suture were performed and a
      posterior pyelography confirmed fistula closure. Presently, he is asymptomatic,
      with stabilized graft function. CONCLUSION: Calyceal fistulas are complications
      of difficult resolution. However, the present case demonstrates that with an
      appropriate treatment it is possible to  save a graft with no apparent solution
      at the first place.

PMID- 23117687
TI  - Right renal infarction: a new case report.
AB  - OBJECTIVE: To present a new case of renal infarction. METHODS: We report the case
      of an 84-year-old woman presenting with right flank colic pain of 24 hours of
      evolution and past history of acute myocardial  infarction four months before.
      CONCLUSION: Renal infarction is a rare condition; in most of the cases it does
      not show specific symptoms and usually overlap with other more common urologic
      procedures, which results in a delay in diagnosis and treatment. The most
      conclusive imaging tests are  i.v contrast CT scan or Doppler ultrasound but
      definitive diagnosis is achieved by angiography or CT angiography. Treatment is
      conservative, with parenteral  and oral anticoagulation; invasive management is
      rare.

PMID- 23117688
TI  - Adrenal ganglioneuroma.
AB  - OBJECTIVE: To present one case of adrenal ganglioneuroma incidentally diagnosed
      in an adult. METHODS/RESULTS: 44-year-old woman with a 2.3 cm incidentaloma in
      the left adrenal gland diagnosed by CT scan. At 6 months, MRI was performed and a
      left adrenal nodule 3.7 cm  was shown. Due to the progressive growth of the
      mass, surgery was indicated and left laparoscopic adrenalectomy was carried out.
      The final pathologic diagnosis was adrenal ganglioneuroma. CONCLUSIONS: The
      ganglioneuroma is a tumor composed of Schwann cells and ganglion cells. Its
      location in the adrenal gland is unusual, most frequently affecting other 
      regions. Being asymptomatic lesions, they are often detected incidentally when
      performing imaging tests. There are radiological features that differentiate them
      from other  adrenal masses. The treatment of choice is surgery, with
      adrenalectomy.

PMID- 23117689
TI  - Intraurethral foreign body.

PMID- 23117690
TI  - Giant urethral diverticulum.

PMID- 23117692
TI  - Single-port laparoscopic cholecystectomy versus standard multiport laparoscopic
      cholecystectomy: a case-control study comparing the long-term quality of life and
      body image.
AB  - PURPOSE: To study the postoperative quality of life and body image of patients
      who underwent either single-port cholecystectomy (SPC) or standard multiport
      laparoscopic cholecystectomy (SMLC) in a long-term assessment. METHODS: Fifty
      patients who underwent SPC using the reusable X-ConeTM Laparoscopic Device were
      compared with a matched group (age, sex, body mass index) of 50 patients after
      SMLC. The health-related quality of life (HRQOL) and body image at 17 months
      postoperatively (median, range 9-23) was analysed by means of the Short-Form 12
      Health Survey and the Body Image Questionnaire, respectively. RESULTS: Both
      patient groups had comparable baseline characteristics, clinical courses, and
      postoperative complication rates. SPC patients were significantly more satisfied
      with the cosmetic result of their scar at 17 months postoperatively, in
      comparison to SMLC patients (cosmetic scale: 22.6 +/- 2.8 vs. 19.5 +/- 3.7, p <
      0.001). However, the HRQOL did not differ between the SPC and SMLC patients
      (physical component scale: 50.0 +/- 8.9 vs. 48.8 +/- 9.4, p = 0.48; mental
      component scale: 53.8 +/- 6.5 vs. 51.3 +/- 8.5, p = 0.10). CONCLUSION: Although
      the overall postoperative HRQOL was comparable, this study suggests that the
      cosmetic result of SPC after complete wound healing is superior to the standard
      multiport laparoscopic procedure.

PMID- 23117693
TI  - Evaluation of Amigas Latinas Motivando el Alma (ALMA): a pilot promotora
      intervention focused on stress and coping among immigrant Latinas.
AB  - Recent immigrant Latinas are at increased risk of poor mental health due to
      stressors associated with adapting to life in the United States. This study
      evaluated Amigas Latinas Motivando el Alma, a promotora intervention to reduce
      stress and promote health and coping among recent immigrant Latinas. Using a pre-
      and post-test design, we evaluated mental health outcomes, specifically, in
      promotoras. Promotoras' knowledge levels related to role of promotora and stress
      management increased, depressive symptoms and stress levels decreased, and coping
      responses and perceived social support increased as well. Results suggest that
      promotora programs may be an effective way to improve mental health in recent
      immigrant Latinas. 

PMID- 23117694
TI  - What we know and don't know about mental health problems among immigrants in
      Norway.
AB  - Mental health problems have been regarded as one of the main public health
      challenges of immigrants in several countries. Understanding and generating
      research-based knowledge on immigrant health problems is highly relevant for
      planning preventive interventions, as well as guiding social and policy actions.
      This review aims to map the available knowledge on immigrants' mental health
      status and its associated risk factors in Norway. The reviewed literature about
      mental health problems among immigrant populations in Norway was found through
      databases, such as PUBMED, EMBASE, PsychINFO and MEDLINE. About 41 peer-reviewed
      original articles published since 1990s were included. In the majority of the
      studies, the immigrant populations, specifically adult immigrants from low and
      middle income countries, have been found with a higher degree of mental health
      problems compared to Norwegians and the general population. Increased risk for
      mental illness is primarily linked to a higher risk for acculturative stress,
      poor social support, deprived socioeconomic conditions, multiple negative life
      events, experiences of discrimination and traumatic pre-migration experiences.
      However, research in this field has been confronted by a number of gaps and
      methodological challenges. The available knowledge indicates a need for
      preventive interventions. Correspondingly, it strongly recommends a comprehensive
      research program that addresses gaps and methodological challenges. 

PMID- 23117695
TI  - Viral tracing of genetically defined neural circuitry.
AB  - Classical methods for studying neuronal circuits are fairly low throughput.
      Transsynaptic viruses, particularly the pseudorabies (PRV) and rabies virus
      (RABV), and more recently vesicular stomatitis virus (VSV), for studying
      circuitry, is becoming increasingly popular. These higher throughput methods use
      viruses that transmit between neurons in either the anterograde or retrograde
      direction. Recently, a modified RABV for monosynaptic retrograde tracing was
      developed. (Figure 1A). In this method, the glycoprotein (G) gene is deleted from
      the viral genome, and resupplied only in targeted neurons. Infection specificity
      is achieved by substituting a chimeric G, composed of the extracellular domain of
      the ASLV-A glycoprotein and the cytoplasmic domain of the RABV-G (A/RG), for the
      normal RABV-G(1). This chimeric G specifically infects cells expressing the TVA
      receptor(1). The gene encoding TVA can been delivered by various methods(2-8).
      Following RABV-G infection of a TVA-expressing neuron, the RABV can transmit to
      other, synaptically connected neurons in a retrograde direction by nature of its
      own G which was co-delivered with the TVA receptor. This technique labels a
      relatively large number of inputs (5-10%)(2) onto a defined cell type, providing
      a sampling of all of the inputs onto a defined starter cell type. We recently
      modified this technique to use VSV as a transsynaptic tracer(9). VSV has several
      advantages, including the rapidity of gene expression. Here we detail a new viral
      tracing system using VSV useful for probing microcircuitry with increased
      resolution. While the original published strategies by Wickersham et al.(4) and
      Beier et al.(9) permit labeling of any neurons that project onto initially
      infected TVA-expressing-cells, here VSV was engineered to transmit only to TVA
      expressing cells (Figure 1B). The virus is first pseudotyped with RABV-G to
      permit infection of neurons downstream of TVA-expressing neurons. After infecting
      this first population of cells, the virus released can only infect TVA-expressing
      cells. Because the transsynaptic viral spread is limited to TVA-expressing cells,
      presence of absence of connectivity from defined cell types can be explored with
      high resolution. An experimental flow chart of these experiments is shown in
      Figure 2. Here we show a model circuit, that of direction-selectivity in the
      mouse retina. We examine the connectivity of starburst amacrine cells (SACs) to
      retinal ganglion cells (RGCs).

PMID- 23117696
TI  - The value of osteopontin in the assessment of bone mineral density status in
      postmenopausal women.
AB  - BACKGROUND: Osteopontin (OPN) has been implicated in bone remodeling by
      activating the resorption process. We aimed to study the relationship between
      OPN, bone mineral density (BMD), bone turnover markers, vitamin D, and
      osteoporotic vertebral fractures in postmenopausal women. MATERIALS AND METHODS:
      Serum levels of OPN, osteocalcin, collagen type 1 cross-linked C-telopeptide
      (CTX), bone alkaline phosphatase, and vitamin D were assessed in 214
      postmenopausal women. Bone mineral density was assessed by dual-energy x-ray
      absorptiometry in lumbar spine and femoral neck, and osteoporotic vertebral
      fractures by radiographs. RESULTS: Osteopontin levels were significantly higher
      in osteoporosis group versus osteopenic and normal group (all P < 0.05). The
      cutoff values of OPN for osteoporosis diagnosis were of 9.47 MUg/L at the lumbar
      spine (area under the curve, 0.67; 95% confidence interval, 0.58-0.75; P < 0.001)
      and 10.15 MUg/L at the femoral neck (area under the curve, 0.69; 95% confidence
      interval, 0.624-0.77; P = 0.0001), respectively. Postmenopausal women with
      osteoporosis-related vertebral fractures had significantly higher levels of OPN
      than those without vertebral fractures (15.69 +/- 13.26 vs 12.63 +/- 12.46 MUg/L;
      P = 0.02). Significant negative correlations were found between OPN and BMD,
      which persisted after the adjustment for age at the lumbar spine. Osteopontin
      levels were directly correlated with bone turnover markers (osteocalcin, bone
      alkaline phosphatase, and CTX). No significant correlation was found between OPN
      and vitamin D. Multiple regression analysis showed that age, waist circumference,
      and CTX were independent predictors of serum OPN levels. CONCLUSIONS: High levels
      of OPN in postmenopausal women are associated with low BMD, increased levels of
      bone turnover markers, and osteoporotic vertebral fractures. These findings
      suggest that OPN might play some role in the pathophysiology of postmenopausal
      osteoporosis and warrant further clinical investigations.

PMID- 23117697
TI  - Acute and chronic effects of exercise on circulating endothelial progenitor cells
      in healthy and diseased patients.
AB  - Exercise is known to improve endothelial function in healthy subjects as well as
      patients with cardiovascular disease and this might be partially related to a
      regeneration of diseased endothelium by circulating progenitor cells (EPCs). EPCs
      are a subgroup of peripheral blood monocytes that contribute to re
      endothelialization of injured endothelium as well as neovascularization of
      ischemic lesions. Cross-sectional studies have indicated that chronic, regular
      physical activity has a positive effect on the levels of circulating EPCs. This
      is associated with an improvement of endothelial dysfunction that is induced by
      apoptosis due to the underlying aging process or accelerated by cardiovascular
      risk factors. Furthermore, it is well established that chronic exercise training
      has the potency to mobilize EPCs from the bone marrow. For patients with cardiac
      disease this is of clinical importance since EPCs have been implicated in
      vascular repair and revascularization. Studies are needed to refine the best mode
      of exercise training that will upregulate circulating EPCs as well as to clarify
      the kinetics of EPCs after the termination of different exercise sessions in
      different diseases and medication. Whether there is a direct link between
      enhanced mobilization of EPCs via exercise and improvement of disease and
      prognosis remains a hypothesis which needs to be further evaluated.

PMID- 23117699
TI  - Phylogenetic comparison of opine dehydrogenase sequences from marine
      invertebrates.
AB  - Three cDNA sequences encoding putative opine dehydrogenase (OpDH) enzymes from
      the mussel Mytilus galloprovincialis were obtained. The deduced amino acid
      sequences were clearly distinguishable from each other, showing that several OpDH
      transcripts could occur in the mussel tissues (p distance 0.46-0.55). When these
      sequences were aligned and compared with published databank proteins, the range
      of identity among the M. galloprovincialis OpDH and the strombine dehydrogenase
      from Ostrea edulis was 51-59 %, the best hit in the three comparisons, followed
      by OpDH enzymes from other marine invertebrates. Sequence alignment revealed
      structural motifs possibly related to the binding sites of the substrates. A
      phylogenetic analysis compared M. galloprovincialis OpDH and annotated sequences
      belonging to five phyla and seven taxonomic classes, including 19 species,
      representing the five OpDH protein family members. The phylogenetic tree
      clustered the OpDH enzymes according to the evolutionary relationships of the
      species and not to the biochemical reaction catalyzed.

PMID- 23117698
TI  - Prevalence of cardiovascular diseases in HIV-infected outpatients: results from a
      prospective, multicenter cohort study.
AB  - BACKGROUND: Recent studies suggest a rising rate of cardiovascular disease (CVD)
      in HIV-infected subjects. Although most countries have an aging HIV-infected
      population, there remains a lack of knowledge about associated cardiovascular
      diseases. METHODS: This ongoing prospective multicentre observational cohort
      study aims to elucidate CVD prevalence in HIV-infected outpatients by
      standardized non-invasive cardiovascular screening. Cardiovascular and coronary
      risk was calculated using Framingham risk scores. RESULTS: 803 HIV-infected
      subjects (mean age 44.2 years, female 16.6 %) were included. The prevalence of
      CVD in HIV-infected subjects was 10.1 % (95 % CI 8.0-12.2 %). Aging HIV-infected
      patients (>=45 years, N = 348) exhibited significantly increased rates of CVD,
      including an elevated frequency of coronary artery disease (7.5 vs. 1.8 %, p <
      0.001), myocardial infarction (6.0 vs. 1.8 %, p = 0.002) and peripheral arterial
      diseases (4.6 vs. 1.5 %, p < 0.017). Furthermore, aging patients exhibited a
      higher rate of chronic heart failure (5.2 vs. 1.5 %, p < 0.001), predominantly of
      ischemic etiology. In multivariate analyses, age (OR 2.05 per decade, 95 % CI
      1.64-2.56), smoking (OR 5.96 per decade, 95 % CI 2.31-15.38) and advanced
      symptomatic HIV infection (OR 2.60 per decade, 95 % CI 1.31-5.15), were
      significantly associated with the prevalence of CVD. Based on the 10-year
      cardiovascular risk estimation, a disproportionate increase in cardiac events has
      to be expected in aging HIV-infected subjects in the next decades (>=45 years/<45
      years 16.4 vs. 4.2 %, p < 0.001). CONCLUSION: CVD in aging HIV-infected
      population is an increasing medical challenge. In the era of antiretroviral
      therapy, prevention and diagnostic strategies are essential to reduce the
      prevalence of CVD in HIV-infected patients.

PMID- 23117700
TI  - PEG-capped, lanthanide doped GdF3 nanoparticles: luminescent and T2 contrast
      agents for optical and MRI multimodal imaging.
AB  - A facile method for the synthesis of water dispersible Er(3+)/Yb(3+) and
      Tm(3+)/Yb(3+) doped upconverting GdF(3) nanoparticles is reported. Strong
      upconversion emissions are observed in the red (for Er/Yb doped) and near
      infrared (for Tm/Yb doped) regions upon laser excitation at 980 nm. The PEG
      coating ensures a good dispersion of the system in water and reduces the
      radiationless de-excitation of the excited states of the Er(3+) and Tm(3+) ions
      by water molecules. The r(2) relaxivity values are quite high with respect to the
      common T(2)-relaxing agents (22.6 +/- 3.4 mM(-1) s(-1) and 15.8 +/- 3.4 mM(-1) s(
      1) for the Tm/Yb and Er/Yb doped samples, respectively), suggesting that the
      present NPs can be interesting as T(2) weighted contrast agents for proton MRI
      purpose. Preliminary experiments conducted in vitro, in stem cell cultures, and
      in vivo, after subcutaneous injection of the lanthanide-doped GdF(3) NPs,
      indicate scarce toxic effects. After an intravenous injection in mice, the GdF(3)
      NPs localize mainly in the liver. The present results indicate that the present
      Er(3+)/Yb(3+) and Tm(3+)/Yb(3+) doped GdF(3) NPs are suitable candidates to be
      efficiently used as bimodal probes for both in vitro and in vivo optical and
      magnetic resonance imaging.

PMID- 23117715
TI  - [Dabigatran: beyond the RE-LY study].

PMID- 23117716
TI  - [Scope of the latest RE-LY substudies: clinical implications].
AB  - The approval of the use of dabiatran in stroke prevention in patients with
      nonvalvular atrial fibrilation (NVAF) is based on the results of the RE-LY
      (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial, one of the
      largest studies to date in this entity. In this trial, dabigatran showed similar
      safety and efficacy to warfarin in primary and secondary prevention of stroke in
      patients with AF. At a dose of 150 mg twice daily, dabigatran was superior to
      warfarin in the prevention of stroke or systemic embolism and the 110 mg dose
      twice daily showed similar efficacy and greater safety, given the lower incidence
      of hemorrhage. These results were consistently found in the various subanalyses,
      with some slight differences of interest for clinical practice. The ideal
      candidates for dabiatran are patients with NVAF suitable for cardioversion, who
      require short periods of anticoagulation, patients in remote geographical areas
      with difficulty in achieving good anticoagulation control or good control with
      anti-vitamin K treatment due to IRN fluctuations, and patients with a low risk of
      hemorrhage and a CHADS score >= 3 and/or with prior stroke, whenever there are no
      contraindications. The choice of dabigatran dose should be evaluated according to
      the patient's individual characteristics (caution must be exercised when
      prescribing this drug in the elderly and in renal insufficiency) and embolic
      and/or hemorrhagic risk. Studies of the long-term safety of this drug,
      pharmacoeconomic analyses in Spain and post-commercialization pharmacovigilance
      data are required before the definitive uses of this drug can be established.

PMID- 23117714
TI  - Reported medication events in a paediatric emergency research network: sharing to
      improve patient safety.
AB  - OBJECTIVE: Medication errors are an important cause of preventable morbidity,
      especially in children in emergency department (ED) settings. Internal use of
      voluntary incident reporting (IR) is common within hospitals, with little
      external reporting or sharing of this information across institutions. We
      describe the analysis of paediatric medication events (ME) reported in 18 EDs in
      a paediatric research network in 2007-2008. METHODS: Confidential, deidentified
      incident reports (IRs) were collected, and MEs were independently categorised by
      two investigators. Discordant responses were resolved by consensus. RESULTS: MEs
      (597) accounted for 19% of all IRs, with reporting rates varying 25-fold across
      sites. Anti-infective agents were the most commonly reported, followed by
      analgesics, intravenous fluids and respiratory medicines. Of the 597 MEs, 94%
      were medication errors and 6% adverse reactions; further analyses are reported
      for medication errors. Incorrect medication doses were related to incorrect
      weight (20%), duplicate doses (21%), and miscalculation (22%). Look-alike/sound
      alike MEs were 36% of incorrect medications. Human factors contributed in 85% of
      reports: failure to follow established procedures (41%), calculation (13%) or
      judgment (12%) errors, and communication failures (20%). Outcomes were: no deaths
      or permanent disability, 13% patient harm, 47% reached patient (no harm), 30%
      near miss or unsafe conditions, and 9% unknown. CONCLUSIONS: ME reporting by the
      system revealed valuable data across sites on medication categories and potential
      human factors. Harm was infrequently reported. Our analyses identify trends and
      latent systems issues, suggesting areas for future interventions to reduce
      paediatric ED medication errors.

PMID- 23117717
TI  - [Dabigatran: transforming the management of oral anticoagulation].
AB  - The utility of oral anticoagulation with warfarin in thromboembolic disease has
      been demonstrated for several decades, although these drugs have significant
      problems in terms of adequate control, interactions and risk of bleeding. In the
      last decade, new anticoagulants have emerged. The first was dabigatran with a
      demonstrated anticoagulant effect approaching the ideal anticoagulant profile.
      The view that dabigatran transforms oral anticoagulation therapy has arisen from
      the RE-VOLUTION program, with more than 34000 patients analyzed. This program has
      confirmed the value of oral anticoagulation with dabigatran compared with other
      anticoagulants; this drug eliminates all the drawbacks of warfarin, benefitting
      both patients and the healthcare system. The growth of the aging population has
      increased the number of risk situations in which anticoagulation is used. There
      is now a drug that meets the criteria for the ideal anticoagulant, transforming
      the management of oral anticoagulation. The findings demonstrated with dabigatran
      in prior studies are progressively being transferred to clinical practice.
      Following the usual development of new drugs, and according to the latest
      Laurence Desmond stages, results in agreement with those of previous studies are
      expected, namely, indisputable improvements in oral anticoagulation for patients
      and the health system.

PMID- 23117718
TI  - Fine genetic mapping of RXopJ4, a bacterial spot disease resistance locus from
      Solanum pennellii LA716.
AB  - The RXopJ4 resistance locus from the wild accession Solanum pennellii (Sp) LA716
      confers resistance to bacterial spot disease of tomato (S. lycopersicum, Sl)
      caused by Xanthomonas perforans (Xp). RXopJ4 resistance depends on recognition of
      the pathogen type III effector protein XopJ4. We used a collection of Sp
      introgression lines (ILs) to narrow the RXopJ4 locus to a 4.2-Mb segment on the
      long arm of chromosome 6, encompassed by the ILs 6-2 and 6-2-2. We then adapted
      or developed a collection of 14 molecular markers to map on a segregating F(2)
      population from a cross between the susceptible parent Sl FL8000 and the
      resistant parent RXopJ4 8000 OC(7). In the F(2) population, a 190-kb segment
      between the markers J350 and J352 cosegregated with resistance. This fine mapping
      will enable both the identification of candidate genes and the detection of
      resistant plants using cosegregating markers. The RXopJ4 resistance gene(s), in
      combination with other recently characterized genes and a quantitative trait
      locus (QTL) for bacterial spot disease resistance, will likely be an effective
      tool for the development of durable resistance in cultivated tomato.

PMID- 23117719
TI  - QUES, a new Phaseolus vulgaris genotype resistant to common bean weevils,
      contains the Arcelin-8 allele coding for new lectin-related variants.
AB  - In common bean (Phaseolus vulgaris L.), the most abundant seed proteins are the
      storage protein phaseolin and the family of closely related APA proteins
      (arcelin, phytohemagglutinin and alpha-amylase inhibitor). High variation in APA
      protein composition has been described and the presence of arcelin (Arc) has been
      associated with bean resistance against two bruchid beetles, the bean weevil
      (Acanthoscelides obtectus Say) and the Mexican bean weevil (Zabrotes subfasciatus
      Bohemian). So far, seven Arc variants have been identified, all in wild
      accessions, however, only those containing Arc-4 were reported to be resistant to
      both species. Although many efforts have been made, a successful breeding of this
      genetic trait into cultivated genotypes has not yet been achieved. Here, we
      describe a newly collected wild accession (named QUES) and demonstrate its
      resistance to both A. obtectus and Z. subfasciatus. Immunological and proteomic
      analyses of QUES seed protein composition indicated the presence of new Arc and
      arcelin-like (ARL) polypeptides of about 30 and 27 kDa, respectively. Sequencing
      of cDNAs coding for QUES APA proteins confirmed that this accession contains new
      APA variants, here referred to as Arc-8 and ARL-8. Moreover, bioinformatic
      analysis showed the two proteins are closely related to APA components present in
      the G12949 wild bean accession, which contains the Arc-4 variant. The presence of
      these new APA components, combined with the observations that they are poorly
      digested and remain very abundant in A. obtectus feces, so-called frass, suggest
      that the QUES APA locus is involved in the bruchid resistance. Moreover,
      molecular analysis indicated a lower complexity of the locus compared to that of
      G12949, suggesting that QUES should be considered a valuable source of resistance
      for further breeding purposes.

PMID- 23117720
TI  - Recent emergence of the wheat Lr34 multi-pathogen resistance: insights from
      haplotype analysis in wheat, rice, sorghum and Aegilops tauschii.
AB  - Spontaneous sequence changes and the selection of beneficial mutations are
      driving forces of gene diversification and key factors of evolution. In highly
      dynamic co-evolutionary processes such as plant-pathogen interactions, the
      plant's ability to rapidly adapt to newly emerging pathogens is paramount. The
      hexaploid wheat gene Lr34, which encodes an ATP-binding cassette (ABC)
      transporter, confers durable field resistance against four fungal diseases.
      Despite its extensive use in breeding and agriculture, no increase in virulence
      towards Lr34 has been described over the last century. The wheat genepool
      contains two predominant Lr34 alleles of which only one confers disease
      resistance. The two alleles, located on chromosome 7DS, differ by only two exon
      polymorphisms. Putatively functional homoeologs and orthologs of Lr34 are found
      on the B-genome of wheat and in rice and sorghum, but not in maize, barley and
      Brachypodium. In this study we present a detailed haplotype analysis of
      homoeologous and orthologous Lr34 genes in genetically and geographically diverse
      selections of wheat, rice and sorghum accessions. We found that the resistant
      Lr34 haplotype is unique to the wheat D-genome and is not found in the B-genome
      of wheat or in rice and sorghum. Furthermore, we only found the susceptible Lr34
      allele in a set of 252 Ae. tauschii genotypes, the progenitor of the wheat D
      genome. These data provide compelling evidence that the Lr34 multi-pathogen
      resistance is the result of recent gene diversification occurring after the
      formation of hexaploid wheat about 8,000 years ago.

PMID- 23117721
TI  - Physical activity prevents progression for cognitive impairment and vascular
      dementia: results from the LADIS (Leukoaraiosis and Disability) study.
AB  - BACKGROUND AND PURPOSE: We aimed to study if physical activity could interfere
      with progression for cognitive impairment and dementia in older people with white
      matter changes living independently. METHODS: The LADIS (Leukoaraiosis and
      Disability) prospective multinational European study evaluates the impact of
      white matter changes on the transition of independent elderly subjects into
      disability. Subjects were evaluated yearly during 3 years with a comprehensive
      clinical protocol and cognitive assessment with classification of cognitive
      impairment and dementia according to usual clinical criteria. Physical activity
      was recorded during the clinical interview. MRI was performed at entry and at the
      end of the study. RESULTS: Six hundred thirty-nine subjects were included (74.1+/
      5 years old, 55% women, 9.6+/-3.8 years of schooling, 64% physically active). At
      the end of follow-up, 90 patients had dementia (vascular dementia, 54; Alzheimer
      disease with vascular component, 34; frontotemporal dementia, 2), and 147 had
      cognitive impairment not dementia. Using Cox regression analysis, physical
      activity reduced the risk of cognitive impairment (dementia and not dementia:
      beta=-0.45, P=0.002; hazard ratio, 0.64; 95% CI, 0.48-0.85), dementia (beta=
      0.49, P=0.043; hazard ratio, 0.61; 95% CI, 0.38-0.98), and vascular dementia
      (beta=-0.86, P=0.008; hazard ratio, 0.42; 95% CI, 0.22-0.80), independent of age,
      education, white matter change severity, medial temporal atrophy, previous and
      incident stroke, and diabetes. CONCLUSIONS: Physical activity reduces the risk of
      cognitive impairment, mainly vascular dementia, in older people living
      independently.

PMID- 23117722
TI  - Early insulin glycemic control combined with tPA thrombolysis reduces acute brain
      tissue damages in a focal embolic stroke model of diabetic rats.
AB  - BACKGROUND AND PURPOSE: Therapeutic effects of early insulin glycemic control for
      poststroke hyperglycemia in combination with tissue-type plasminogen activator
      (tPA) thrombolytic therapy have not yet been studied but are of great clinical
      interest. In this study, we tested the effects of insulin plus tPA combination in
      a model of focal embolic stroke in Type I diabetic rats. METHODS: Streptozotocin
      was used to produce Type I diabetes in male Wistar rats for 6 weeks and then
      embolic focal strokes were induced. All rats were treated with insulin or saline
      at 1 hour followed by tPA or saline at 1.5 hour after stroke. Mortality,
      infarction, hemispheric swelling, hemorrhagic transformation, and perfusion
      defects were examined at 24 hours after stroke. Total plasma plasminogen
      activator inhibitor-1 antigen and activity levels were measured before stroke and
      1.5, 3, and 6 hours after stroke by ELISA. RESULTS: Early insulin glycemic
      control alone or tPA thrombolysis alone had no significant effects on ischemic
      infarction. However, early insulin glycemic control combined with tPA
      significantly reduced brain infarction and swelling, ameliorated tPA-associated
      hemorrhagic transformation, and improved plasma perfusion at 24 hours after
      stroke. We also found that the combination significantly decreased plasma
      plasminogen activator inhibitor-1 antigen level at 6 hours and plasminogen
      activator inhibitor-1 activity at 1.5 and 6 hours after stroke. CONCLUSIONS:
      Early insulin glycemic control may be beneficial in combination with tPA
      thrombolysis for ischemic stroke with diabetes mellitus or poststroke
      hyperglycemia.

PMID- 23117723
TI  - Venous thromboembolism risk in ischemic stroke patients receiving extended
      duration enoxaparin prophylaxis: results from the EXCLAIM study.
AB  - BACKGROUND AND PURPOSE: The optimal duration of venous thromboembolism
      prophylaxis in acute stroke patients is unknown. This subanalysis of the Extended
      Prophylaxis for Venous ThromboEmbolism in Acutely Ill Medical Patients With
      Prolonged Immobilization (EXCLAIM) study investigated extended-duration
      thromboprophylaxis with enoxaparin, compared with placebo following standard
      duration enoxaparin, in ischemic stroke patients. METHODS: Acutely ill medical
      patients with recently reduced mobility received open-label enoxaparin 40 mg for
      10+/-4 days, and they were then randomized to double-blind enoxaparin 40 mg daily
      or placebo for further 28+/-4 days. Venous thromboembolism incidence
      (symptomatic/asymptomatic deep-vein thrombosis, symptomatic/fatal pulmonary
      embolism) up to day 28 after randomization and major bleeding rates up to 48 h
      after the last dose of study treatment were reported. RESULTS: In total, 389 of
      5963 (6.5%) randomized patients had ischemic stroke: 198 received extended
      duration prophylaxis and 191 placebo. Extended-duration prophylaxis reduced
      venous thromboembolism incidence versus placebo (2.4% versus 8.0%; absolute risk
      difference, -5.6%; 95% CI, -10.5% to -0.7%), but it was associated with an
      increase in major bleeding (1.5% versus 0% in enoxaparin and placebo groups;
      absolute risk difference, +1.5%; 95% CI, -0.2% to 3.2%). CONCLUSIONS: Extended
      duration thromboprophylaxis with enoxaparin was associated with reduced venous
      thromboembolism risk and increased major bleeding in the subgroup of patients
      with ischemic stroke in the EXCLAIM study.

PMID- 23117724
TI  - Randomized controlled trial of symptomatic middle cerebral artery stenosis:
      endovascular versus medical therapy in a Chinese population.
AB  - BACKGROUND AND PURPOSE: To investigate the efficacy and safety of percutaneous
      transluminal angioplasty and stenting (PTAS) for symptomatic middle cerebral
      artery stenosis compared with standard medical treatment in a low-risk Chinese
      population. METHODS: A prospective, randomized, controlled, single-center
      clinical trial was conducted comparing PTAS with medical treatment for
      symptomatic middle cerebral artery stenosis (>=70%). Patients were enrolled
      according to 1:1 enroll ratio (PTAS: medical). The PTAS group received stenting
      or balloon angioplasty, whereas the medical treatment group received standard
      medical treatment (aspirin 100mg plus clopidogrel 75 mg/d), and all the patients
      were under strict control of the risk factors. The end point events were any kind
      of ipsilateral stroke or transient ischemic attack, or death from any origin
      during 1-year follow-up. RESULTS: The enrollment was stopped after 70 patients
      were enrolled from August 2007 to December 2010, with a 30-day rate of end point
      events of 8.3% versus 5.9% (P=0.69) for PTAS and medical group, respectively, and
      1-year rate of end point events of 19.4% versus 17.6% (P=0.85), respectively.
      There was no significant difference in baseline characteristics between the 2
      groups. The mean follow-up time, which was ongoing, was 9.9+/-3.9 and 9.7+/-4.4
      months, respectively. Among the risk factors, hypertension was the independent
      related to the outcome (P=0.015). CONCLUSIONS: This study showed that
      endovascular treatment is as safe but not better than medical treatment for
      symptomatic middle cerebral artery stenosis in a low-risk Chinese population.
      History of hypertension increases the risk of recurrent ischemic events.

PMID- 23117726
TI  - [Programs, objectives and hopes for the next biennium].

PMID- 23117725
TI  - Secondary intracerebral hemorrhage due to early initiation of oral
      anticoagulation after ischemic stroke: an experimental study in mice.
AB  - BACKGROUND AND PURPOSE: The uncertain risk of secondary intracerebral hemorrhage
      (sICH) frequently keeps clinicians from initiating oral anticoagulation (OAC)
      early after ischemic cardioembolic stroke. The goal of this experimental study
      was to determine the risk of sICH depending on the timing of OAC initiation
      relative to stroke onset and to address the role of hematogenous macrophages for
      repair processes preventing OAC-associated sICH. METHODS: C57BL/6 mice were
      subjected to transient middle cerebral artery occlusion. Subgroups were treated
      with either the vitamin K antagonist (VKA) phenprocoumon or the direct thrombin
      inhibitor dabigatran etexilate. Hematogenous macrophages were depleted using
      intraperitoneal injections of clodronate-filled liposomes. RESULTS: Time to
      therapeutic OAC was 48 hours with VKA and 0.5 hours with dabigatran etexilate
      treatment. In VKA-treated mice, the risk of sICH was high if effective OAC was
      already present at stroke onset or achieved within 48 hours after ischemia. With
      more delayed OAC, the risk of sICH rapidly decreased. Compared with VKA
      treatment, effective anticoagulation with dabigatran etexilate was associated
      with a significantly reduced extent of sICH, either if present at stroke onset or
      if achieved 48 hours later. Partial depletion of macrophages greatly increased
      the extent of OAC-associated sICH in the subacute stage of 3 to 4 days after
      ischemia. CONCLUSIONS: Our findings suggest that repair mechanisms involving
      hematogenous macrophages rapidly decrease the risk of OAC-associated sICH in the
      first days after ischemic stroke. The lower risk of sICH under dabigatran
      etexilate compared with VKA treatment may facilitate early initiation of OAC
      after cardioembolic stroke.

PMID- 23117727
TI  - [Tubular progenitor cells: new protagonists of tubular regeneration].

PMID- 23117728
TI  - [Hyperphosphatemia in moderate CKD: a paradox of modern nephrology].

PMID- 23117729
TI  - [Acute tubular necrosis: a matter of image!].

PMID- 23117730
TI  - [Relationship between creatinine standardization and glomerular filtration rate
      estimation].

PMID- 23117731
TI  - [Early management of CKD-MBD: from theory to practice].

PMID- 23117732
TI  - [Children of a lesser God or miracles? Reflections on children born to mothers on
      dialysis].

PMID- 23117733
TI  - [A tale of two cells].

PMID- 23117734
TI  - [Pre-emptive renal transplantation from deceased donor].
AB  - Preemptive transplantation from deceased donors is an important issue due to its
      ethical and clinical implications. In this paper, two nephrologists discuss the
      problem from different angles, expressing their opinion on specific points and
      highlighting the limitations and advantages. The first point discussed relates to
      the advantages of preemptive renal transplant from a deceased donor versus
      dialysis. The second point considers the possibility that the former could reduce
      the already limited resources for patients on the transplant waiting list. The
      third point discusses whether preemptive transplant should be reserved for
      patients with particular background diseases. The last discussion point relates
      to the possibility that a preemptive program from deceased donors could hamper an
      already limited living donor program. The ethical aspects are examined separately
      by a bioethicist who critically evaluates all discussion points and lists some
      principles that should guide clinicians, before or after starting dialysis, in
      the proper use of renal transplant, an efficacious but scarce resource.

PMID- 23117735
TI  - [New mechanisms and recent insights in the pathogenesis of acute kidney injury
      (AKI)].
AB  - Acute kidney injury (AKI) is a frequent complication in hospitalized patients
      often associated with multiple organ failure, increased mortality and progression
      toward chronic kidney disease. The identification of new cellular and molecular
      targets involved in AKI may lead to an improvement of diagnostic and therapeutic
      approaches. In recent years, the pathogenetic mechanisms of AKI have been fully
      elucidated: tubular epithelial cells and endothelial cells present in the
      microvasculature have been identified as the main targets of ischemia and of
      nephrotoxic drugs. Indeed, endothelial cell injury is associated with an
      extension phase of AKI, whereas tubular cells are subjected to an alteration of
      cell polarity, mislocalization of tight junction proteins and membrane
      transporters, and finally to the development of necrosis or apotosis. Apoptosis,
      or programmed cell death, is also a key component of sepsis-associated AKI in
      which the mechanisms of tissue damage are associated not only with hypoperfusion
      but also with a direct detrimental effect of bacterial products and inflammatory
      mediators on resident kidney cells. Endothelial and tubular epithelial cells also
      represent the main targets in the immunological mechanisms of AKI in kidney
      transplantation during cell-mediated and antibody-mediated rejection. Recent
      studies evidenced new molecules as early biomarkers of AKI. Among these
      molecules, NGAL and KIM-1 play a possible role in the progression toward chronic
      kidney disease. Lastly, the new frontier of AKI therapy is represented by the use
      of bone marrow-derived mesenchymal stem cells able to induce a regenerative
      program in the damaged kidney.

PMID- 23117736
TI  - [Ultrafiltration in heart failure].
AB  - In patients with heart failure fluid overload is clinically evident as systemic
      and/or pulmonary congestion, and represents a key issue in the therapeutic
      approach to the syndrome. Ultrafiltration, obtained by dedicated machines or
      standard dialysis machines (isolated ultrafiltration), or by the use of the
      peritoneal membrane (peritoneal ultrafiltration), has been recently proposed for
      fluid overload correction. This review is aimed at illustrating the operative
      background, safety, efficacy and cost issues of the different ultrafiltration
      modalities in heart failure. We retrieved all full-text non-duplicated articles
      documenting clinical studies on ultrafiltration in heart failure and describing
      patient characteristics, ultrafiltration procedures, renal outcome and adverse
      effects, by searching MEDLINE, EMBASE and the Cochrane Central Register of
      Controlled Trials up to December 31, 2011, with the terms ''heart failure'' and
      ''ultrafiltration OR hemofiltration'' and ''heart failure'' and "peritoneal
      dialysis". Isolated ultrafiltration can be considered potentially safe for the
      heart and the kidney in heart failure, and is efficacious for fluid overload
      removal. However, the available evidence does not support its widespread use as a
      substitute for conventional diuretic therapy. Isolated ultrafiltration should be
      employed neither as a quicker way to achieve mechanical diuresis nor as a remedy
      for an apparently inadequate response to conventional diuretic therapy.
      Peritoneal ultrafiltration is a promising ultrafiltration procedure that can be
      safely and successfully performed in heart failure; however, also in this case
      larger-scale randomized controlled trials are needed. The available evidence
      supports the concept of reserving ultrafiltration modalities for selected
      patients with advanced heart failure and true diuretic resistance, as part of a
      more integrated strategy aimed at fluid overload control.

PMID- 23117737
TI  - [Hepatorenal syndrome].
AB  - Hepatorenal syndrome (HRS) is defined by progressive changes in the splanchnic
      and systemic circulation of cirrhosis patients. It is usually secondary to
      triggering events, inducing a complex multiorgan dysfunction syndrome, also
      including renal failure with a reduction in urinary output. The progression rate
      of the renal dysfunction discriminates between HRS type 1, where the worsening is
      more rapid, i.e. 1-2 weeks, and type 2, where instead it has a slower
      progression. The sympathetic nervous system, the renin-angiotensin system,
      antidiuretic hormone, cytokines and endothelial factors are all involved at the
      same time and are mutually interactive. Sodium and water retention, with ascites,
      edema and dilutional hyponatremia on the one hand and glomerular filtration
      inhibition due to intrarenal vasoconstriction on the other, are the main clinical
      manifestations. In the past, HRS resolution was dependent on the possibility of a
      liver transplant, which is usually followed by the restoration of normal renal
      function. Nowadays, pharmacological therapy based on the use of vasoconstrictors
      adds new steps to HRS treatment. Terlipressin, an analogue of vasopressin, in
      combination with albumin may lead to renal recovery in 40-60% of patients.
      Moreover, in the bridge phase to transplantation, the new systems for the
      extracoporeal depuration of the renal failure solutes and protein-bound solutes
      typical of liver failure could increase the short-term patient survival. HRS
      alone should not be considered an indication for combined kidney-liver
      transplant. In patients with advanced cirrhosis, the prevention of complications
      possibly triggering HRS is based on prophylactic antibiotics in order to avoid
      contamination of the ascitic fluid and albumin to increase the plasma volume.

PMID- 23117738
TI  - [Immunosuppressive treatment after kidney transplant: the frontier of chronic
      antibody-mediated rejection].
AB  - The recognition of antibody-mediated rejection as an important factor in the
      reduction of long-term renal graft survival represents a new challenge to the
      immunosuppressive strategies of recent years, which have been quite successful in
      reducing the acute rejection rates as well as the side effects of pharmacological
      immunosuppression. The search for an effective treatment of chronic anti-donor
      antibody disease has been pursued mostly through limited single-center
      experiences and therefore in a dispersed fashion, without leading to the
      definition of a consolidated approach. The most frequently used pharmacological
      approaches stem from the experience of antibody-mediated acute rejection. In this
      review we will critically analyze the results reported so far of various
      intervention strategies and we will discuss future pharmacological novelties
      targeting the humoral immune response.

PMID- 23117739
TI  - [Guiding the patient with end-stage renal disease in the choice of replacement
      therapy: role of the predialysis outpatient department].
AB  - The predialysis outpatient department has three main objectives: ensuring
      patients' conscious and informed choice of dialysis treatment; clinical followup
      of patients with stage IV-V kidney disease; supporting patients and their
      families in their treatment choice. The aim of this work is to evaluate a) the
      effectiveness of the predialysis outpatient department in informing patients
      about the problems inherent in their disease; b) the differences in the choice of
      dialysis treatment between patients who benefited from the predialysis program
      and those who did not have that opportunity. Ninety-six patients were included in
      the study: 77 started renal replacement therapy after following a program at the
      predialysis outpatient department, while the remaining 19 patients started
      dialysis in an unplanned way. The patients monitored during predialysis were
      given a questionnaire to evaluate the usefulness of the followed program. The 77
      patients who attended the predialysis outpatient department proved to be equally
      divided between hemodialysis and peritoneal dialysis: 43% vs 57%; the other 19
      patients were directed mainly towards hemodialysis: 86% vs 14%, respectively.
      Analysis of the questionnaires showed that patients expressed a good degree of
      satisfaction. The results pointed to the usefulness of creating a predialysis
      outpatient department that should be able to a) optimize the predialytic
      treatments; b) plan the preparation of vascular or peritoneal access; c)
      guarantee patients a conscious choice of their replacement therapy.

PMID- 23117740
TI  - [Ultrasound and color Doppler in nephrology. Acute kidney injury].
AB  - At present, ultrasonography (US) is not able to define the type of renal damage
      and therefore cannot replace percutaneous renal biopsy in the diagnosis of acute
      kidney disease. It is, however, the most immediate and safest imaging technique
      for the evaluation of patients with acute kidney injury (AKI) in order to exclude
      urinary tract obstruction or chronic kidney disease and guide clinical decision
      making. In prerenal AKI caused by cardiorenal syndrome type 1, US does not show
      specific signs. However, in these patients, pleuropulmonary US is the first
      choice imaging technique to evaluate the congestion of subpleural interlobular
      septa and to identify and count lung comet tails. In cardiorenal syndrome type 2,
      US visualizes signs of systemic overload (right pleural effusion, liver stasis,
      overdistention and rigidity of the inferior vena cava and suprahepatic veins). In
      acute tubular necrosis (ATN), the most common type of AKI, gray-scale US is
      nonspecific and shows enlarged kidneys with hypoechoic pyramids due to medullary
      edema. The resistance index (RI) is a very useful marker to establish the
      severity of ATN and the required follow-up, and to evaluate functional recovery,
      since its reduction precedes the normalization of serum creatinine. US is the
      technique of choice in the diagnosis of obstructive nephropathy, where it is
      highly sensitive (>95%) but less specific (<70%). The primary objective of this
      review is to analyze the applications of US in the diagnosis of prerenal, renal
      and postrenal AKI.

PMID- 23117741
TI  - [A case of intrarenal hematoma: role of ultrasonography in the early diagnosis of
      a possible complication of anticoagulant therapy].
AB  - Uremia associated with anticoagulant therapy is a high risk factor for bleeding
      complications in patients undergoing hemodialysis. We report a case of intrarenal
      hematoma arising in a uremic patient treated with warfarin. The hematoma was
      rapidly diagnosed by ultrasonography of the abdomen and treated with
      embolization. Our experience confirms that the availability of an ultrasound
      facility within the renal unit allows better assessment of our patients, also in
      the management of the most fearsome and rare complications. Moreover, it
      strengthens the evidence that uremic patients are at high risk of bleeding
      complications when treated with oral anticoagulants.

PMID- 23117742
TI  - [Renal biopsy practice in Piedmont and Valle d'Aosta].
AB  - In 2010 a questionnaire was administered to the renal units of Piedmont and Valle
      d'Aosta to analyze their procedures for renal biopsy (RB). Seventy-eight percent
      of units performed RBs, 57% for more than 20 years, but only 43% performed at
      least 20 BRs per year. 20/21 units performed RB in an inpatient setting and 1/21
      in day hospital with the patient remaining under observation the night after.
      Thirty-two percent did not consider a single kidney as a contraindication to RB,
      59% considered it a relative contraindication and 9% considered it an absolute
      contraindication. In 90.5% of units there was a specific protocol for patient
      preparation for RB and 86% used a specific informed consent form. Ninety-five
      percent of units performed ultrasound-guided RB, 60% of them using needle guides
      attached to the probe. In 81% of units the left side was preferred; 71% put a
      pillow under the patient's abdomen. All units used disposable, automated or semi
      automated needles. Needle size was 16G in 29%, 18G in 58%, and both 16G and 18G
      in 14% of units; 1 to 3 samples were drawn. One third of units had a microscope
      available for immediate evaluation of specimen adequacy. After RB, 86% of units
      kept patients in the prone position for 2-6 hours and all prescribed a period of
      bed rest (at least 24 hours in 90.5%). 90.5% of units followed a specific
      postbiopsy observation protocol consisting of blood pressure, heart rate and red
      blood cell measurements at different times, and urine monitoring and ultrasound
      control within 12-24 hours (only half of them also employing color Doppler). One
      third of all units discharged patients after 1 day and two thirds after 2-3 days;
      all prescribed abstention from effort and from antiplatelet drugs for 7-15 days.
      In 9 units both RB and tissue processing and examination were done in the same
      hospital, while 12 units sent the samples elsewhere. 76% obtained results in 2-4
      days, 19% in 6-7 days, and 5% in 10-15 days. Less than 20% of the interviewed
      operators were fully familiar with the clauses of hospital insurance securing
      their activity. Use of RB is widespread in Piedmont and Valle d'Aosta but its
      practice shows variation between centers.

PMID- 23117743
TI  - [Interview with Prof. Giuseppe Bianchi, nephrologist with a passion for
      hypertension. Interview by Mario Timio].

PMID- 23117744
TI  - Who benefits from statins? Patient or focal plaque?

PMID- 23117745
TI  - Balanced mineralization in the arterial system: possible role of
      osteoclastogenesis/osteoblastogenesis in abdominal aortic aneurysm and stenotic
      disease.
AB  - Arterial calcification is the result of the same highly organized processes as
      seen in bone, which rely on a delicate balance between osteoblasts and
      osteoclasts. Although previously understood as passive precipitation, evidence
      has accumulated to suggest that arterial calcification is the result of
      organized, regulated processes bearing many similarities to osteogenesis in bone,
      including the presence of subpopulations of arterial wall cells that retain
      osteoblastic lineage potential. These cells have the potential to form
      mineralized nodules and express osteoblast markers, including bone morphogenetic
      protein-2, osteocalcin, osteopontin, and alkaline phosphatase. By contrast,
      osteoclast-like cells mediate the catabolic process of mineral resorption. Recent
      data shows that cells positive for tartrate-resistant acid phosphatase, a major
      marker for osteoclasts, have been histologically identified in atherosclerotic
      lesions and are referred to as osteoclast-like cells. Evidence has accumulated to
      suggest that initial arterial calcification through passive precipitation of
      calcium phosphate initiates balanced mineralization regulated by osteoclast-like
      and osteoblast-like cells. Subsequently, various pathogenic conditions may
      trigger an imbalance between osteoblastogenesis and osteoclastogenesis, leading
      to either calcification in stenotic/occlusive disease or destruction of the
      extracellular matrix in aneurysmal disease. Further elucidation of these newly
      emerging concepts could lead to a novel therapeutic approach to arterial
      stenotic/occlusive disease and/or abdominal aortic aneurysm.

PMID- 23117747
TI  - Patch clamp recordings in inner ear hair cells isolated from zebrafish.
AB  - Patch clamp analyses of the voltage-gated channels in sensory hair cells isolated
      from a variety of species have been described previously(1-4) but this video
      represents the first application of those techniques to hair cells from
      zebrafish. Here we demonstrate a method to isolate healthy, intact hair cells
      from all of the inner ear end-organs: saccule, lagena, utricle and semicircular
      canals. Further, we demonstrate the diversity in hair cell size and morphology
      and give an example of the kinds of patch clamp recordings that can be obtained.
      The advantage of the use of this zebrafish model system over others stems from
      the availability of zebrafish mutants that affect both hearing and balance. In
      combination with the use of transgenic lines and other techniques that utilize
      genetic analysis and manipulation, the cell isolation and electrophysiological
      methods introduced here should facilitate greater insight into the roles hair
      cells play in mediating these sensory modalities.

PMID- 23117746
TI  - Tryptase-positive mast cells and angiogenesis in keloids: a new possible post
      surgical target for prevention.
AB  - Literature data indicate that mast cells (MCs) are involved in angiogenesis
      through the release of several pro-angiogenetic factors among which tryptase, a
      serine protease stored in MC granules, is one of the most active. However, no
      data are available concerning the role of MCs during keloids' angiogenesis. In
      this study, we evaluated the correlations of the number of MCs positive to
      tryptase (MCDPT) and microvascular density (MVD) within a series of 15 keloids
      and 10 normotrophic scars, by means of immunohistochemistry and image analysis
      methods. Data demonstrated a significant difference of MVD and MCDPT between
      keloids and normotrophic scars and a significant correlation between MVD and
      MCDPT in keloids. Our results suggest that tryptase-positive MCs might play a key
      role in keloids' angiogenesis. In this context, several tryptase inhibitors might
      be clinically evaluated as a possible new anti-angiogenetic approach to prevent
      keloid formation after surgery.

PMID- 23117748
TI  - Formation of model hepatocellular aggregates in a hydrogel scaffold using
      degradable genipin crosslinked gelatin microspheres as cell carriers.
AB  - Primary hepatocyte is probably the preferred cell for cell therapy in liver
      regeneration. However, its non-ideal proliferation capacity and rapid loss of
      phenotype during 2D culture compromises the quality and quantity of the
      transplanted hepatocytes, resulting in variable success rates of this treatment.
      Many studies have shown that the formation of 3D hepatocellular spheroids aids in
      the maintenance of liver-specific functions in hepatocytes. However, many of the
      methodologies employed require a sophisticated set-up or specialized equipment
      which makes it uneconomical to scale up for clinical applications. In this study,
      we have developed dual-functioning genipin crosslinked gelatin microspheres that
      serve as cell carriers as well as porogens for delivering the model cells and
      also for creating cavities. The cells were first seeded onto genipin crosslinked
      gelatin microspheres for attachment, followed by encapsulation in alginate
      hydrogel. Collagenase, MMP-9, was introduced either in the culture media or mixed
      with alginate precursor solution to allow microsphere degradation for creating
      cavities within the gel bulk. Accordingly, the cells proliferate within the
      cavities, forming hepatocellular aggregates while the alginate hydrogel serves as
      a confinement, restricting the size and the shape of the aggregates to the size
      of the cavities. In addition, the final hepatocellular aggregates could be
      harvested from the system by removing the alginate hydrogel via citrate
      treatment. Therefore, this versatile platform not only has the advantage of
      injectability and simplicity, the cellular aggregates generated are in a
      controlled size and shape and can be extracted from the system.

PMID- 23117755
TI  - New basic care goals seek to rein in global rise in cardiovascular disease.

PMID- 23117752
TI  - The cover: Ritratto del Cuore (portrait of the heart).

PMID- 23117756
TI  - MRSA may move from livestock to humans.

PMID- 23117749
TI  - Auricular transcutaneous electrical nerve stimulation in depressed patients: a
      randomized controlled pilot study.
AB  - Invasive vagus nerve stimulation has been demonstrated to be an effective
      treatment in major depressive episodes. Recently, a novel non-invasive method of
      stimulating the vagus nerve on the outer canal of the ear has been proposed. In
      healthy subjects, a prominent fMRI BOLD signal deactivation in the limbic system
      was found. The present pilot study investigates the effects of this novel
      technique of auricular transcutaneous electric nerve stimulation in depressed
      patients for the first time. A total of 37 patients suffering from major
      depression were included in two randomized sham controlled add-on studies.
      Patients were stimulated five times a week on a daily basis for the duration of 2
      weeks. On days 0 and 14, the Hamilton Depression Rating Scale (HAMD) and the Beck
      Depression Inventory (BDI) were assessed. In contrast to sham-treated patients,
      electrically stimulated persons showed a significantly better outcome in the BDI.
      Mean decrease in the active treatment group was 12.6 (SD 6.0) points compared to
      4.4 (SD 9.9) points in the sham group. HAMD score did not change significantly in
      the two groups. An antidepressant effect of a new transcutaneous auricular nerve
      stimulation technique has been shown for the first time in this controlled pilot
      study. Regarding the limitations of psychometric testing, the risk of unblinding
      for technical reasons, and the small sample size, further studies are necessary
      to confirm the present results and verify the practicability of tVNS in clinical
      fields.

PMID- 23117757
TI  - New anticoagulants offer options beyond warfarin to reduce stroke risk.

PMID- 23117765
TI  - Physical activity to combat depression in chronic heart failure.

PMID- 23117767
TI  - Vein-graft harvesting technique in coronary artery bypass graft surgery.

PMID- 23117769
TI  - Inclusion of comparative effectiveness data in high-risk cardiovascular device
      studies at the time of premarket approval.

PMID- 23117771
TI  - Transforming clinical trials in cardiovascular disease: mission critical for
      health and economic well-being.

PMID- 23117772
TI  - Preventing and controlling hypertension in the era of genomic innovation and
      environmental transformation.

PMID- 23117773
TI  - The future of cardiovascular clinical research: informatics, clinical
      investigators, and community engagement.

PMID- 23117774
TI  - A piece of my mind. On caring for those who will remain.

PMID- 23117775
TI  - Multivitamins in the prevention of cardiovascular disease in men: the Physicians'
      Health Study II randomized controlled trial.
AB  - CONTEXT: Although multivitamins are used to prevent vitamin and mineral
      deficiency, there is a perception that multivitamins may prevent cardiovascular
      disease (CVD). Observational studies have shown inconsistent associations between
      regular multivitamin use and CVD, with no long-term clinical trials of
      multivitamin use. OBJECTIVE: To determine whether long-term multivitamin
      supplementation decreases the risk of major cardiovascular events among men.
      DESIGN, SETTING, AND PARTICIPANTS: The Physicians' Health Study II, a randomized,
      double-blind, placebo-controlled trial of a common daily multivitamin, began in
      1997 with continued treatment and follow-up through June 1, 2011. A total of
      14,641 male US physicians initially aged 50 years or older (mean, 64.3 [SD, 9.2]
      years), including 754 men with a history of CVD at randomization, were enrolled.
      INTERVENTION: Daily multivitamin or placebo. MAIN OUTCOME MEASURES: Composite end
      point of major cardiovascular events, including nonfatal myocardial infarction
      (MI), nonfatal stroke, and CVD mortality. Secondary outcomes included MI and
      stroke individually. RESULTS: During a median follow-up of 11.2 (interquartile
      range, 10.7-13.3) years, there were 1732 confirmed major cardiovascular events.
      Compared with placebo, there was no significant effect of a daily multivitamin on
      major cardiovascular events (11.0 and 10.8 events per 1000 person-years for
      multivitamin vs placebo, respectively; hazard ratio [HR], 1.01; 95% CI, 0.91
      1.10; P = .91). Further, a daily multivitamin had no effect on total MI (3.9 and
      4.2 events per 1000 person-years; HR, 0.93; 95% CI, 0.80-1.09; P = .39), total
      stroke (4.1 and 3.9 events per 1000 person-years; HR, 1.06; 95% CI, 0.91-1.23; P
      = .48), or CVD mortality (5.0 and 5.1 events per 1000 person-years; HR, 0.95; 95%
      CI, 0.83-1.09; P = .47). A daily multivitamin was also not significantly
      associated with total mortality (HR, 0.94; 95% CI, 0.88-1.02; P = .13). The
      effect of a daily multivitamin on major cardiovascular events did not differ
      between men with or without a baseline history of CVD (P = .62 for interaction).
      CONCLUSION: Among this population of US male physicians, taking a daily
      multivitamin did not reduce major cardiovascular events, MI, stroke, and CVD
      mortality after more than a decade of treatment and follow-up. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00270647.

PMID- 23117776
TI  - Intraoperative high-dose dexamethasone for cardiac surgery: a randomized
      controlled trial.
AB  - CONTEXT: Prophylactic corticosteroids are often administered during cardiac
      surgery to attenuate the inflammatory response to cardiopulmonary bypass and
      surgical trauma; however, evidence that routine corticosteroid use can prevent
      major adverse events is lacking. OBJECTIVE: To quantify the effect of
      intraoperative high-dose dexamethasone on the incidence of major adverse events
      in patients undergoing cardiac surgery. DESIGN, SETTING, AND PARTICIPANTS: A
      multicenter, randomized, double-blind, placebo-controlled trial of 4494 patients
      aged 18 years or older undergoing cardiac surgery with cardiopulmonary bypass at
      8 cardiac surgical centers in The Netherlands enrolled between April 13, 2006,
      and November 23, 2011. INTERVENTION: Patients were randomly assigned to receive a
      single intraoperative dose of 1 mg/kg dexamethasone (n = 2239) or placebo (n =
      2255). MAIN OUTCOME MEASURES: A composite of death, myocardial infarction,
      stroke, renal failure, or respiratory failure, within 30 days of randomization.
      RESULTS: Of the 4494 patients who underwent randomization, 4482 (99.7%) could be
      evaluated for the primary outcome. A total of 157 patients (7.0%) in the
      dexamethasone group and 191 patients (8.5%) in the placebo group reached the
      primary study end point (relative risk, 0.83; 95% CI, 0.67-1.01; absolute risk
      reduction, -1.5%; 95% CI, -3.0% to 0.1%; P = .07). Dexamethasone was associated
      with reductions in postoperative infection, duration of postoperative mechanical
      ventilation, and lengths of intensive care unit and hospital stays. In contrast,
      dexamethasone was associated with higher postoperative glucose levels.
      CONCLUSION: In our trial of adults undergoing cardiac surgery, the use of
      intraoperative dexamethasone did not reduce the 30-day incidence of major adverse
      events compared with placebo. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT00293592.

PMID- 23117777
TI  - Association of race and sex with risk of incident acute coronary heart disease
      events.
AB  - CONTEXT: It is unknown whether long-standing disparities in incidence of coronary
      heart disease (CHD) among US blacks and whites persist. OBJECTIVE: To examine
      incident CHD by black and white race and by sex. DESIGN, SETTING, AND
      PARTICIPANTS: Prospective cohort study of 24,443 participants without CHD at
      baseline from the Reasons for Geographic and Racial Differences in Stroke
      (REGARDS) cohort, who resided in the continental United States and were enrolled
      between 2003 and 2007 with follow-up through December 31, 2009. MAIN OUTCOME
      MEASURE: Expert-adjudicated total (fatal and nonfatal) CHD, fatal CHD, and
      nonfatal CHD (definite or probable myocardial infarction [MI]; very small non-ST
      elevation MI [NSTEMI] had peak troponin level <0.5 MUg/L). RESULTS: Over a mean
      (SD) of 4.2 (1.5) years of follow-up, 659 incident CHD events occurred (153 in
      black men, 138 in black women, 254 in white men, and 114 in white women). Among
      men, the age-standardized incidence rate per 1000 person-years for total CHD was
      9.0 (95% CI, 7.5-10.8) for blacks vs 8.1 (95% CI, 6.9-9.4) for whites; fatal CHD:
      4.0 (95% CI, 2.9-5.3) vs 1.9 (95% CI, 1.4-2.6), respectively; and nonfatal CHD:
      4.9 (95% CI, 3.8-6.2) vs 6.2 (95% CI, 5.2-7.4). Among women, the age-standardized
      incidence rate per 1000 person-years for total CHD was 5.0 (95% CI, 4.2-6.1) for
      blacks vs 3.4 (95% CI, 2.8-4.2) for whites; fatal CHD: 2.0 (95% CI, 1.5-2.7) vs
      1.0 (95% CI, 0.7-1.5), respectively; and nonfatal CHD: 2.8 (95% CI, 2.2-3.7) vs
      2.2 (95% CI, 1.7-2.9). Age- and region-adjusted hazard ratios for fatal CHD among
      blacks vs whites was near 2.0 for both men and women and became statistically
      nonsignificant after multivariable adjustment. The multivariable-adjusted hazard
      ratio for incident nonfatal CHD for blacks vs whites was 0.68 (95% CI, 0.51-0.91)
      for men and 0.81 (95% CI, 0.58-1.15) for women. Of the 444 nonfatal CHD events,
      139 participants (31.3%) had very small NSTEMIs. CONCLUSIONS: The higher risk of
      fatal CHD among blacks compared with whites was associated with cardiovascular
      disease risk factor burden. These relationships may differ by sex.

PMID- 23117779
TI  - Platelet function during extended prasugrel and clopidogrel therapy for patients
      with ACS treated without revascularization: the TRILOGY ACS platelet function
      substudy.
AB  - CONTEXT: The relationship of platelet function testing measurements with outcomes
      in patients with acute coronary syndromes (ACS) initially managed medically
      without revascularization is unknown. OBJECTIVE: To characterize the differences
      and evaluate clinical outcomes associated with platelet reactivity among patients
      with ACS treated with clopidogrel or prasugrel. DESIGN, SETTING, AND PATIENTS:
      Patients with medically managed unstable angina or non-ST-segment elevation
      myocardial infarction were enrolled in the TRILOGY ACS trial (2008 to 2011)
      comparing clopidogrel vs prasugrel. Of 9326 participants, 27.5% were included in
      a platelet function substudy: 1286 treated with prasugrel and 1278 treated with
      clopidogrel. INTERVENTIONS: Aspirin with either prasugrel (10 or 5 mg/d) or
      clopidogrel (75 mg/d); those 75 years or older and younger than 75 years but who
      weighed less than 60 kg received a 5-mg prasugrel maintenance dose. MAIN OUTCOME
      MEASURES: Platelet reactivity, measured in P2Y12 reaction units (PRUs), was
      performed at baseline, at 2 hours, and at 1, 3, 6, 12, 18, 24, and 30 months
      after randomization. The primary efficacy end point was a composite of
      cardiovascular death, myocardial infarction, or stroke through 30 months.
      RESULTS: Among participants younger than 75 years and weighing 60 kg or more, the
      median PRU values at 30 days were 64 (interquartile range [IQR], 33-128) in the
      prasugrel group vs 200 (IQR, 141-260) in the clopidogrel group (P < .001), a
      difference that persisted through all subsequent time points. For participants
      younger than 75 years and weighing less than 60 kg, the median 30-day PRU values
      were 139 (IQR, 86-203) for the prasugrel group vs 209 (IQR, 148-283) for the
      clopidogrel group (P < .001), and for participants 75 years or older, the median
      PRU values were 164 (IQR, 105-216) for the prasugrel group vs 222 (IQR, 148-268)
      for the clopidogrel group (P < .001). At 30 months the rate of the primary
      efficacy end point was 17.2% (160 events) in the prasugrel group vs 18.9% (180
      events) in the clopidogrel group (P = .29). There were no significant differences
      in the continuous distributions of 30-day PRU values for participants with a
      primary efficacy end point event after 30 days (n = 214) compared with
      participants without an event (n = 1794; P = .07) and no significant relationship
      between the occurence of the primary efficacy end point and continuous PRU values
      (adjusted hazard ratio [HR] for increase of 60 PRUs, 1.03; 95% CI, 0.96-1.11; P =
      .44). Similar findings were observed with 30-day PRU cut points used to define
      high on-treatment platelet reactivity-PRU more than 208 (adjusted HR, 1.16; 95%
      CI, 0.89-1.52, P = .28) and PRU more than 230 (adjusted HR, 1.20; 95% CI, 0.90
      1.61; P = .21). CONCLUSIONS: Among patients with ACS without ST-segment elevation
      and initially managed without revascularization, prasugrel was associated with
      lower platelet reactivity than clopidogrel, irrespective of age, weight, and
      dose. Among those in the platelet substudy, no significant differences existed
      between prasugrel vs clopidogrel in the occurence of the primary efficacy end
      point through 30 months and no significant association existed between platelet
      reactivity and occurrence of ischemic outcomes. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00699998.

PMID- 23117778
TI  - Prevalence of major cardiovascular risk factors and cardiovascular diseases among
      Hispanic/Latino individuals of diverse backgrounds in the United States.
AB  - CONTEXT: Major cardiovascular diseases (CVDs) are leading causes of mortality
      among US Hispanic and Latino individuals. Comprehensive data are limited
      regarding the prevalence of CVD risk factors in this population and relations of
      these traits to socioeconomic status (SES) and acculturation. OBJECTIVES: To
      describe prevalence of major CVD risk factors and CVD (coronary heart disease
      [CHD] and stroke) among US Hispanic/Latino individuals of different backgrounds,
      examine relationships of SES and acculturation with CVD risk profiles and CVD,
      and assess cross-sectional associations of CVD risk factors with CVD. DESIGN,
      SETTING, AND PARTICIPANTS: Multicenter, prospective, population-based Hispanic
      Community Health Study/Study of Latinos including individuals of Cuban (n =
      2201), Dominican (n = 1400), Mexican (n = 6232), Puerto Rican (n = 2590), Central
      American (n = 1634), and South American backgrounds (n = 1022) aged 18 to 74
      years. Analyses involved 15,079 participants with complete data enrolled between
      March 2008 and June 2011. MAIN OUTCOME MEASURES: Adverse CVD risk factors defined
      using national guidelines for hypercholesterolemia, hypertension, obesity,
      diabetes, and smoking. Prevalence of CHD and stroke were ascertained from self
      reported data. RESULTS: Age-standardized prevalence of CVD risk factors varied by
      Hispanic/Latino background; obesity and current smoking rates were highest among
      Puerto Rican participants (for men, 40.9% and 34.7%; for women, 51.4% and 31.7%,
      respectively); hypercholesterolemia prevalence was highest among Central American
      men (54.9%) and Puerto Rican women (41.0%). Large proportions of participants
      (80% of men, 71% of women) had at least 1 risk factor. Age- and sex-adjusted
      prevalence of 3 or more risk factors was highest in Puerto Rican participants
      (25.0%) and significantly higher (P < .001) among participants with less
      education (16.1%), those who were US-born (18.5%), those who had lived in the
      United States 10 years or longer (15.7%), and those who preferred English
      (17.9%). Overall, self-reported CHD and stroke prevalence were low (4.2% and 2.0%
      in men; 2.4% and 1.2% in women, respectively). In multivariate-adjusted models,
      hypertension and smoking were directly associated with CHD in both sexes as were
      hypercholesterolemia and obesity in women and diabetes in men (odds ratios [ORs],
      1.5-2.2). For stroke, associations were positive with hypertension in both sexes,
      diabetes in men, and smoking in women (ORs, 1.7-2.6). CONCLUSION: Among US
      Hispanic/Latino adults of diverse backgrounds, a sizeable proportion of men and
      women had adverse major risk factors; prevalence of adverse CVD risk profiles was
      higher among participants with Puerto Rican background, lower SES, and higher
      levels of acculturation.

PMID- 23117781
TI  - Multivitamins in prevention of cardiovascular disease.

PMID- 23117780
TI  - Lifetime risk and years lived free of total cardiovascular disease.
AB  - CONTEXT: Estimates of lifetime risk for total cardiovascular disease (CVD) may
      provide projections of the future population burden of CVD and may assist in
      clinician-patient risk communication. To date, no lifetime risk estimates of
      total CVD have been reported. OBJECTIVES: To calculate lifetime risk estimates of
      total CVD by index age (45, 55, 65, 75 years) and risk factor strata and to
      estimate years lived free of CVD across risk factor strata. DESIGN, SETTING, AND
      PARTICIPANTS: Pooled survival analysis of as many as 905,115 person-years of data
      from 1964 through 2008 from 5 National Heart, Lung, and Blood Institute-funded
      community-based cohorts: Framingham Heart Study, Framingham Offspring Study,
      Atherosclerosis Risk in Communities Study, Chicago Heart Association Detection
      Project in Industry Study, and Cardiovascular Health Study. All participants were
      free of CVD at baseline with risk factor data (blood pressure [BP], total
      cholesterol [TC], diabetes, and smoking status) and total CVD outcome data. MAIN
      OUTCOME MEASURES: Any total CVD event (including fatal and nonfatal coronary
      heart disease, all forms of stroke, congestive heart failure, and other CVD
      deaths). RESULTS: At an index age of 45 years, overall lifetime risk for total
      CVD was 60.3% (95% CI, 59.3%-61.2%) for men and 55.6% (95% CI, 54.5%-56.7%) for
      women. Men had higher lifetime risk estimates than women across all index ages.
      At index ages 55 and 65 years, men and women with at least 1 elevated risk factor
      (BP, 140-149/90-99 mm Hg; or TC, 200-239 mg/dL; but no diabetes or smoking), 1
      major risk factor, or at least 2 major risk factors (BP, >=160/100 mm Hg or
      receiving treatment; TC, >=240 mg/dL or receiving treatment; diabetes mellitus;
      or current smoking) had lifetime risk estimates to age 95 years that exceeded
      50%. Despite an optimal risk factor profile (BP, <120/80 mm Hg; TC, <180 mg/dL;
      and no smoking or diabetes), men and women at the index age of 55 years had
      lifetime risks (through 85 years of age) for total CVD of greater than 40% and
      30%, respectively. Compared with participants with at least 2 major risk factors,
      those with an optimal risk factor profile lived up to 14 years longer free of
      total CVD. CONCLUSIONS: Lifetime risk estimates for total CVD were high (>30%)
      for all individuals, even those with optimal risk factors in middle age. However,
      maintenance of optimal risk factor levels in middle age was associated with
      substantially longer morbidity-free survival.

PMID- 23117782
TI  - Time for a creative transformation of epidemiology in the United States.

PMID- 23117783
TI  - Measured drug effect and cardiovascular outcomes in patients receiving platelet
      P2Y12 receptor antagonists: clarifying the time and place for intensive
      inhibition.

PMID- 23117784
TI  - Viewing cardiovascular research through the eyes of past, present, and future
      generations.

PMID- 23117789
TI  - JAMA patient page: Stents to treat coronary artery blockages.

PMID- 23117790
TI  - Orexin-A suppresses postischemic glucose intolerance and neuronal damage through
      hypothalamic brain-derived neurotrophic factor.
AB  - Orexin-A (a glucose-sensing neuropeptide in the hypothalamus) and brain-derived
      neurotrophic factor (BDNF; a member of the neurotrophin family) play roles in
      many physiologic functions, including regulation of glucose metabolism. We
      previously showed that the development of postischemic glucose intolerance is one
      of the triggers of ischemic neuronal damage. The aim of this study was to
      determine whether there was an interaction between orexin-A and BDNF functions in
      the hypothalamus after cerebral ischemic stress. Male ddY mice were subjected to
      2 hours of middle cerebral artery occlusion (MCAO). Neuronal damage was estimated
      by histologic and behavioral analyses. Expression of protein levels was analyzed
      by Western blot. Small interfering RNA directed BDNF, orexin-A, and SB334867 [N
      (2-methyl-6-benzoxazolyl)-N'-1,5-naphthyridin-4-yl urea; a specific orexin-1
      receptor antagonist] were administered directly into the hypothalamus. The level
      of hypothalamic orexin-A, detected by immunohistochemistry, was decreased on day
      1 after MCAO. Intrahypothalamic administration of orexin-A (1 or 5 pmol/mouse)
      significantly and dose-dependently suppressed the development of postischemic
      glucose intolerance on day 1 and development of neuronal damage on day 3. The
      MCAO-induced decrease in insulin receptor levels in the liver and skeletal muscle
      on day 1 was recovered to control levels by orexin-A, and this effect of orexin-A
      was reversed by the administration of SB334867 as well as by hypothalamic BDNF
      knockdown. These results suggest that suppression of postischemic glucose
      intolerance by orexin-A assists in the prevention of cerebral ischemic neuronal
      damage. In addition, hypothalamic BDNF may play an important role in this effect
      of orexin-A.

PMID- 23117791
TI  - LAS: a software platform to support oncological data management.
AB  - The rapid technological evolution in the biomedical and molecular oncology fields
      is providing research laboratories with huge amounts of complex and heterogeneous
      data. Automated systems are needed to manage and analyze this knowledge, allowing
      the discovery of new information related to tumors and the improvement of medical
      treatments. This paper presents the Laboratory Assistant Suite (LAS), a software
      platform with a modular architecture designed to assist researchers throughout
      diverse laboratory activities. The LAS supports the management and the
      integration of heterogeneous biomedical data, and provides graphical tools to
      build complex analyses on integrated data. Furthermore, the LAS interfaces are
      designed to ease data collection and management even in hostile environments
      (e.g., in sterile conditions), so as to improve data quality.

PMID- 23117792
TI  - Automatic and adaptive classification of electroencephalographic signals for
      brain computer interfaces.
AB  - Extracting knowledge from electroencephalographic (EEG) signals has become an
      increasingly important research area in biomedical engineering. In addition to
      its clinical diagnostic purposes, in recent years there have been many efforts to
      develop brain computer interface (BCI) systems, which allow users to control
      external devices only by using their brain activity. Once the EEG signals have
      been acquired, it is necessary to use appropriate feature extraction and
      classification methods adapted to the user in order to improve the performance of
      the BCI system and, also, to make its design stage easier. This work introduces a
      novel fast adaptive BCI system for automatic feature extraction and
      classification of EEG signals. The proposed system efficiently combines several
      well-known feature extraction procedures and automatically chooses the most
      useful features for performing the classification task. Three different feature
      extraction techniques are applied: power spectral density, Hjorth parameters and
      autoregressive modelling. The most relevant features for linear discrimination
      are selected using a fast and robust wrapper methodology. The proposed method is
      evaluated using EEG signals from nine subjects during motor imagery tasks.
      Obtained experimental results show its advantages over the state-of-the-art
      methods, especially in terms of classification accuracy and computational cost.

PMID- 23117793
TI  - Implementation of the Josie King Care Journal in a pediatric intensive care unit:
      a quality improvement project.
AB  - The Care Journal is a tool developed by the Josie King Foundation to promote
      interactive exchange among providers and patients/families. The Care Journal was
      implemented in a pediatric intensive care unit, and surveys were administered to
      assess perceptions about use. Parents who used the Care Journal and nursing staff
      found it to be a useful tool that improved communication, made parents feel more
      knowledgeable and empowered, and improved parents' overall perception of the
      hospital stay.

PMID- 23117794
TI  - Frequently observed risk factors for fall-related injuries and effective
      preventive interventions: a multihospital survey of nurses' perceptions.
AB  - There is an urgent need to prioritize the risk factors for injurious falls and
      effective interventions in nursing practice. Registered nurses perceived that the
      most frequently observed risk factors were confusion, gait problems, Alzheimer
      disease, disorientation, and inability to follow safety instructions. The most
      effective interventions were keeping hospital bed brakes locked, keeping floor
      surfaces clean/dry, using appropriate footwear for patients, maintaining a call
      light within reach, and reducing tripping hazards.

PMID- 23117795
TI  - Reversible electroswitchable luminescence in thin films of organic-inorganic
      hybrid assemblies.
AB  - In this study, reversible electroswitched luminescence is realized in a novel
      hybrid composite of organic-inorganic polymers and Pyronin Y-doped silica
      nanoparticles (PYDS) in aqueous solutions for the first time. The electrochromic
      material, poly (3,4-ethylenedioxythiophene) (PEDOT), is electrodeposited on the
      electrode in the presence of phosphododecamolybdic acid (PMo(12)). The
      luminescence of PYDS can be effectively switched between "on" and "off" states by
      applying oxidation and reduction potentials of PEDOT via the corresponding
      luminescence quenching effect. The electrochromic devices (ECDs) we report here
      exhibit lots of advantages, such as easy fabrication, high contrast of
      fluorescence response, good reversibility, and long-time stability. The creative
      application of PEDOT in ECDs in aqueous solutions is anticipated to offer
      important hints and a basis for other organic materials in the field of
      photoelectric devices.

PMID- 23117796
TI  - Complementary fluorescence-polarization microscopy using division-of-focal-plane
      polarization imaging sensor.
AB  - Fluorescence microscopy offers high sensitivity for disease diagnosis. However,
      little structural information is revealed by this method, requiring another
      technique to localize the source of fluorescence. We developed a complementary
      fluorescence-polarization microscope. We used a division-of-focal-plane charge
      coupled device polarization sensor to enable real-time video rate polarization
      imaging without any moving parts. The polarization information provided by the
      microscope enabled detection of structural element and complements the
      fluorescence information. Application of this multimodal system for cancer
      imaging using a tumor selective molecular probe revealed the association of
      diminished structural integrity of tumor tissue with high fluorescence of the
      imaging agent compared to surrounding normal tissue. This study demonstrates a
      new paradigm to improve cancer detection and diagnosis.

PMID- 23117797
TI  - Single-dose safety and pharmacokinetic evaluation of fluorocoxib A: pilot study
      of novel cyclooxygenase-2-targeted optical imaging agent in a canine model.
AB  - We evaluated preclinical single-dose safety, pharmacokinetic properties, and
      specific uptake of the new optical imaging agent fluorocoxib A in dogs.
      Fluorocoxib A, N-[(5-carboxy-X-rhodaminyl)but-4-yl]-2-[1-(4-chlorobenzoyl)-5
      methoxy-2-methyl-1H-indol-3-yl]acetamide, selectively binds and inhibits the
      cyclooxygenase-2 (COX-2) enzyme, which is overexpressed in many cancers. Safety
      pilot studies were performed in research dogs following intravenous (i.v.)
      administration of 0.1 and 1  mg/kg fluorocoxib A. Blood and urine samples
      collected three days after administration of each dose of fluorocoxib A revealed
      no evidence of toxicity, and no clinically relevant adverse events were noted on
      physical examination of exposed dogs over that time period. Pharmacokinetic
      parameters were assessed in additional research dogs from plasma collected at
      several time points after i.v. administration of fluorocoxib A using high
      performance liquid chromatography analysis. The pharmacokinetic studies using 1 
      mg/kg showed a peak of fluorocoxib A (92+/-28  ng/ml) in plasma collected at 0.5
      h. Tumor specific uptake of fluorocoxib A was demonstrated using a dog diagnosed
      with colorectal cancer expressing COX-2. Our data support the safe single-dose
      administration and in vivo efficacy of fluorocoxib A, suggesting a high potential
      for successful translation to clinical use as an imaging agent for improved tumor
      detection in humans.

PMID- 23117798
TI  - In vivo validation of a bimodal technique combining time-resolved fluorescence
      spectroscopy and ultrasonic backscatter microscopy for diagnosis of oral
      carcinoma.
AB  - Tissue diagnostic features generated by a bimodal technique integrating scanning
      time-resolved fluorescence spectroscopy (TRFS) and ultrasonic backscatter
      microscopy (UBM) are investigated in an in vivo hamster oral carcinoma model.
      Tissue fluorescence is excited by a pulsed nitrogen laser and spectrally and
      temporally resolved using a set of filters/dichroic mirrors and a fast digitizer,
      respectively. A 41-MHz focused transducer (37-MUm axial, 65-MUm lateral
      resolution) is used for UBM scanning. Representative lesions of the different
      stages of carcinogenesis show that fluorescence characteristics complement
      ultrasonic features, and both correlate with histological findings. These results
      demonstrate that TRFS-UBM provide a wealth of co-registered, complementary data
      concerning tissue composition and structure as it relates to disease status. The
      direct co-registration of the TRFS data (sensitive to surface molecular changes)
      with the UBM data (sensitive to cross-sectional structural changes and depth of
      tumor invasion) is expected to play an important role in pre-operative diagnosis
      and intra-operative determination of tumor margins.

PMID- 23117800
TI  - Spectral imaging technique for retinal perfusion detection using confocal
      scanning laser ophthalmoscopy.
AB  - To evaluate retinal perfusion in the human eye, a dual-wavelength confocal
      scanning laser ophthalmoscope (cSLO) was developed that provides spectral imaging
      of the fundus using a combination of red (670 nm) and near-infrared (810 nm)
      wavelengths. The image of the ocular fundus was analyzed to find out if
      quantitative measurements of the reflectivity of tissue permit assessment of the
      oxygen perfusion of tissue. We explored problems that affect the reproducibility
      of patient measurements such as non-uniformity errors on the image. For the first
      time, an image processing technique was designed and used to minimize the errors
      of oxygen saturation measurements by illumination correction in retina wide field
      by increasing SNR. Retinal images were taken from healthy and diabetic
      retinopathy eyes using the cSLO with a confocal aperture of 100 MUm. The ratio
      image (RI) of red/IR, as oxygen saturation (SO2) index, was calculated for normal
      eyes. The image correction technique improved the reproducibility of the
      measurements. Average RI intensity variation of healthy retina tissue was
      determined within a range of about 5.5%. The capability of the new technique to
      discriminate oxygenation levels of retinal artery and vein was successfully
      demonstrated and showed good promise in the diagnosis of the perfused retina.

PMID- 23117799
TI  - Automated segmentation algorithm for detection of changes in vaginal epithelial
      morphology using optical coherence tomography.
AB  - We have explored the use of optical coherence tomography (OCT) as a noninvasive
      tool for assessing the toxicity of topical microbicides, products used to prevent
      HIV, by monitoring the integrity of the vaginal epithelium. A novel feature-based
      segmentation algorithm using a nearest-neighbor classifier was developed to
      monitor changes in the morphology of vaginal epithelium. The two-step automated
      algorithm yielded OCT images with a clearly defined epithelial layer, enabling
      differentiation of normal and damaged tissue. The algorithm was robust in that it
      was able to discriminate the epithelial layer from underlying stroma as well as
      residual microbicide product on the surface. This segmentation technique for OCT
      images has the potential to be readily adaptable to the clinical setting for
      noninvasively defining the boundaries of the epithelium, enabling quantifiable
      assessment of microbicide-induced damage in vaginal tissue.

PMID- 23117801
TI  - Assessment of the effects of ultrasound-mediated glucose on permeability of
      normal, benign, and cancerous human lung tissues with the Fourier-domain optical
      coherence tomography.
AB  - The objective of this study was to evaluate the effects of ultrasound-mediated
      analyte diffusion on permeability of normal, benign, and cancerous human lung
      tissue in vitro and to find more effective sonophoretic (SP) delivery in
      combination with the optical clearing agents (OCAs) method to distinguish normal
      and diseased lung tissues. The permeability coefficients of SP in combination
      with OCAs diffusion in lung tissue were measured with Fourier-domain optical
      coherence tomography (FD-OCT). 30% glucose and SP with a frequency of 1 MHz and
      an intensity of 0.80  W/cm2 over a 3 cm probe was simultaneously applied for 15
      min. Experimental results show that the mean permeability coefficients of 30%
      glucose/SP were found to be (2.01+/-0.21)*10(-5)  cm/s from normal lung (NL)
      tissue, (2.75+/-0.28)*10(-5)  cm/s from lung benign granulomatosis (LBG) tissue,
      (4.53+/-0.49)*10(-5)  cm/s from lung adenocarcinoma tumor (LAT) tissue, and
      (5.81+/-0.62)*10(-5)  cm/s from lung squamous cell carcinoma (LSCC) tissue,
      respectively. The permeability coefficients of 30% glucose/SP increase
      approximately 36.8%, 125.4%, and 189.1% for the LBG, LAT, and LSCC tissue
      compared with that for the NL tissue, respectively. There were statistically
      significant differences in permeability coefficients of 30% glucose/SP between
      LBG and NL tissue (p<0.05), between LAT and NL tissue (p<0.05), and between LSCC
      and NL tissue (p<0.05). The results suggest that the OCT functional imaging
      technique to combine an ultrasound-OCAs combination method could become a
      powerful tool in early diagnosis and monitoring of changed microstructure of
      pathologic human lung tissue.

PMID- 23117802
TI  - Evaluation of the role of CD207 on Langerhans cells in a murine model of atopic
      dermatitis by in situ imaging using Cr:forsterite laser-based multimodality
      nonlinear microscopy.
AB  - Atopic dermatitis (AD) is an allergic inflammatory disease of skin. It remains
      unclear that CD207 of Langerhans cells (LCs) plays a central role in the
      development of allergic sensitization. There is little data on LCs within the
      microenviroment in vivo. We used a murine model of epicutaneous (EC) ovalbumin
      (OVA) sensitization inducing an inflammatory skin resembling AD to explore the
      role of CD207 in the pathogenesis of AD. Cr:forsterite laser-based multimodality
      nonlinear microscopy was applied for in situ imaging. Peritoneal injections of
      Alexa Fluor 647-rat anti-mouse CD207 into mice were performed to specifically
      trace the LCs. Peritoneal injections of OVA-Alexa Fluor 647 conjugate into mice
      were performed to specifically trace the OVA. We found that combining Alexa Fluor
      fluorescent probes with multimodality nonlinear microscopy permitted the
      unequivocal in situ imaging of CD207-expressing LCs. The relevant time-course,
      expressional, and functional studies reveal that CD207 of LCs plays an essential
      role during the induction of EC sensitization. We establish and validate that
      Cr:forsterite laser-based multimodality nonlinear microscopy is applicable for
      the specific detection of labeled mAb-bound LCs and labeled antigen. We suggest
      that CD207-expressing LCs initiate the allergic response through the CD207
      mediated epicutaneous sensitization associated with the development of AD.

PMID- 23117803
TI  - Comparison of Schlemm's canal's biological parameters in primary open-angle
      glaucoma and normal human eyes with swept source optical.
AB  - ABSTRACT. Thirty-seven normal and primary open angle glaucoma (POAG) subjects
      were noninvasively imaged by a tailor-made real-time anterior segment swept
      source optical coherence tomography (SS-OCT) to demonstrate the differences of
      the Schlemm's canal (SC) between POAG and normal eyes. After the cross-section
      images of the anterior chamber angle were acquired by SS-OCT, SC was confirmed by
      two independent masked observers and the average area, long diameter, and
      perimeter of the SC were measured. In normal subjects the circumference, area,
      and long diameter is 580.34+/-87.81  MUm, 8023.89+/-1486.10  MUm2, and 272.83+/
      49.39  MUm, respectively, and these parameters were 393.25+/-98.04  MUm,
      3941.50+/-1210.69  MUm2, and 190.91+/-46.47  MUm in the POAG subjects. The area
      of SC in the normal ones was significantly larger than that in POAG eyes
      (p<0.001), so as the long diameter and the perimeter (p<0.001; p<0.001).

PMID- 23117804
TI  - Retinal optical coherence tomography image enhancement via shrinkage denoising
      using double-density dual-tree complex wavelet transform.
AB  - ABSTRACT. Image enhancement of retinal structures, in optical coherence
      tomography (OCT) scans through denoising, has the potential to aid in the
      diagnosis of several eye diseases. In this paper, a locally adaptive denoising
      algorithm using double-density dual-tree complex wavelet transform, a combination
      of the double-density wavelet transform and the dual-tree complex wavelet
      transform, is applied to reduce speckle noise in OCT images of the retina. The
      algorithm overcomes the limitations of commonly used multiple frame averaging
      technique, namely the limited number of frames that can be recorded due to eye
      movements, by providing a comparable image quality in significantly less
      acquisition time equal to an order of magnitude less time compared to the
      averaging method. In addition, improvements of image quality metrics and 5 dB
      increase in the signal-to-noise ratio are attained.

PMID- 23117805
TI  - Epithelium and Bowman's layer thickness and light scatter in keratoconic cornea
      evaluated using ultrahigh resolution optical coherence tomography.
AB  - A custom-developed ultrahigh resolution optical coherence tomography with an
      axial resolution of 1.1 MUm in corneal tissue was used to characterize thickness
      and light scatter of the epithelium and Bowman's layer in keratoconic (KC) cornea
      noninvasively. A 4-mm wide vertical corneal section around the apex in nine KC
      and eight normal eyes was imaged in vivo. The epithelium and Bowman's layer were
      visualized and their thickness profiles were quantified. Scatter was quantified
      based on the sensitivity normalized mean signal intensity distribution. Average
      mean thickness of the epithelium and Bowman's layer in KC eyes was significantly
      smaller (p<0.05) than the normal eyes. The epithelium thickness variation across
      a central 3-mm cornea was significantly larger in KC eyes than in normal eyes.
      The scatter in KC eyes was significantly increased only for Bowman's layer. The
      changes observed in this study could improve our understanding of the underlying
      disease mechanism of KC and can provide new indications for early disease
      diagnosis.

PMID- 23117806
TI  - Label-free assessment of adipose-derived stem cell differentiation using coherent
      anti-Stokes Raman scattering and multiphoton microscopy.
AB  - Adult stem cells (SCs) hold great potential as likely candidates for disease
      therapy but also as sources of differentiated human cells in vitro models of
      disease. In both cases, the label-free assessment of SC differentiation state is
      highly desirable, either as a quality-control technology ensuring cells to be
      used clinically are of the desired lineage or to facilitate in vitro time-course
      studies of cell differentiation. We investigate the potential of nonlinear
      optical microscopy as a minimally invasive technology to monitor the
      differentiation of adipose-derived stem cells (ADSCs) into adipocytes and
      osteoblasts. The induction of ADSCs toward these two different cell lineages was
      monitored simultaneously using coherent anti-Stokes Raman scattering, two photon
      excitation fluorescence (TPEF), and second harmonic generation at different time
      points. Changes in the cell's morphology, together with the appearance of
      biochemical markers of cell maturity were observed, such as lipid droplet
      accumulation for adipo-induced cells and the formation of extra-cellular matrix
      for osteo-induced cells. In addition, TPEF of flavoproteins was identified as a
      proxy for changes in cell metabolism that occurred throughout ADSC
      differentiation toward both osteoblasts and adipocytes. These results indicate
      that multimodal microscopy has significant potential as an enabling technology
      for the label-free investigation of SC differentiation.

PMID- 23117807
TI  - Recognizing different tissues in human fetal femur cartilage by label-free Raman
      microspectroscopy.
AB  - Traditionally, the composition of bone and cartilage is determined by standard
      histological methods. We used Raman microscopy, which provides a molecular
      "fingerprint" of the investigated sample, to detect differences between the zones
      in human fetal femur cartilage without the need for additional staining or
      labeling. Raman area scans were made from the (pre)articular cartilage, resting,
      proliferative, and hypertrophic zones of growth plate and endochondral bone
      within human fetal femora. Multivariate data analysis was performed on Raman
      spectral datasets to construct cluster images with corresponding cluster
      averages. Cluster analysis resulted in detection of individual chondrocyte
      spectra that could be separated from cartilage extracellular matrix (ECM) spectra
      and was verified by comparing cluster images with intensity-based Raman images
      for the deoxyribonucleic acid/ribonucleic acid (DNA/RNA) band. Specific
      dendrograms were created using Ward's clustering method, and principal component
      analysis (PCA) was performed with the separated and averaged Raman spectra of
      cells and ECM of all measured zones. Overall (dis)similarities between measured
      zones were effectively visualized on the dendrograms and main spectral
      differences were revealed by PCA allowing for label-free detection of individual
      cartilaginous zones and for label-free evaluation of proper cartilaginous matrix
      formation for future tissue engineering and clinical purposes.

PMID- 23117808
TI  - Infrared spectral imaging as a novel approach for histopathological recognition
      in colon cancer diagnosis.
AB  - Innovative diagnostic methods are the need of the hour that could complement
      conventional histopathology for cancer diagnosis. In this perspective, we propose
      a new concept based on spectral histopathology, using IR spectral micro-imaging,
      directly applied to paraffinized colon tissue array stabilized in an agarose
      matrix without any chemical pre-treatment. In order to correct spectral
      interferences from paraffin and agarose, a mathematical procedure is implemented.
      The corrected spectral images are then processed by a multivariate clustering
      method to automatically recover, on the basis of their intrinsic molecular
      composition, the main histological classes of the normal and the tumoral colon
      tissue. The spectral signatures from different histological classes of the
      colonic tissues are analyzed using statistical methods (Kruskal-Wallis test and
      principal component analysis) to identify the most discriminant IR features.
      These features allow characterizing some of the biomolecular alterations
      associated with malignancy. Thus, via a single analysis, in a label-free and
      nondestructive manner, main changes associated with nucleotide, carbohydrates,
      and collagen features can be identified simultaneously between the compared
      normal and the cancerous tissues. The present study demonstrates the potential of
      IR spectral imaging as a complementary modern tool, to conventional
      histopathology, for an objective cancer diagnosis directly from paraffin-embedded
      tissue arrays.

PMID- 23117809
TI  - In vivo optical imaging of human vaginal gel thickness distributions with a probe
      based, dual-modality instrument.
AB  - ABSTRACT. We used a probe-based dual-modality optical imaging instrument to
      measure in vivo coating thickness distributions of a gel distributed along the
      vaginal lumen, in a clinical study. The gel was a surrogate for one delivering an
      anti-HIV topical microbicide. Imaging data from Fourier-domain multiplexed low
      coherence interferometry (mLCI) and fluorimetric measurements were compared to
      assess the feasibility and accuracy of mLCI in measuring in vivo gel coating
      thickness distributions. In each study session, 3.5 mL of Replens gel was
      inserted to the vaginal fornix while the participant was supine. The participant
      either: 1. remained supine (10 or 60 min); or 2. sat up (1 min), stood up (1
      min), sat down (1 min) and returned to the supine position; net elapsed time was
      10 or 60 min after which the gel distribution was imaged. Local coating thickness
      distributions were qualitatively and quantitatively similar. Here mLCI did not
      accurately measure thicker gel coatings (>0.8  mm), a limitation not seen with
      fluorimetry. However, mLCI is capable of measuring in vivo microbicide gel
      distributions with resolution on the order of 10 MUm, without the need for
      exogenous contrast agents, and can accurately capture relevant summary coating
      measures in good agreement with fluorimetry.

PMID- 23117810
TI  - Ex vivo optical metabolic measurements from cultured tissue reflect in vivo
      tissue status.
AB  - Optical measurements of metabolism are ideally acquired in vivo; however,
      intravital measurements are often impractical. Accurate ex vivo assessments would
      greatly broaden the applicability of optical measurements of metabolism. We
      investigate the use of live tissue culture experiments to serve as a surrogate
      for in vivo metabolic measurements. To validate this approach, NADH and FAD
      fluorescence intensity and lifetime images were acquired with a two-photon
      microscope from hamster cheek pouch epithelia in vivo, from biopsies maintained
      in live tissue culture up to 48 h, and from flash-frozen and thawed biopsies. We
      found that the optical redox ratio (fluorescence intensity of NADH/FAD) of the
      cultured biopsy was statistically identical to the in vivo measurement until 24
      h, while the redox ratio of the frozen-thawed samples decreased by 15% (p<0.01).
      The NADH mean fluorescence lifetime (taum) remained unchanged (p>0.05) during the
      first 8 h of tissue culture, while the NADH taum of frozen-thawed samples
      increased by 13% (p<0.001). Cellular morphology did not significantly change
      between in vivo, cultured, and frozen-thawed tissues (p>0.05). All results were
      consistent across multiple depth layers in this stratified squamous epithelial
      tissue. Histological markers for proliferation and apoptosis also confirm the
      viability of tissues maintained in culture. This study suggests that short-term
      ex vivo tissue culture may be more appropriate than frozen-thawed tissue for
      optical metabolic and morphologic measurements that approximate in vivo status.

PMID- 23117812
TI  - Respiratory function monitoring using a real-time three-dimensional fiber-optic
      shaping sensing scheme based upon fiber Bragg gratings.
AB  - An array of in-line curvature sensors on a garment is used to monitor the
      thoracic and abdominal movements of a human during respiration. The results are
      used to obtain volumetric changes of the human torso in agreement with a
      spirometer used simultaneously at the mouth. The array of 40 in-line fiber Bragg
      gratings is used to produce 20 curvature sensors at different locations, each
      sensor consisting of two fiber Bragg gratings. The 20 curvature sensors and
      adjoining fiber are encapsulated into a low-temperature-cured synthetic silicone.
      The sensors are wavelength interrogated by a commercially available system from
      Moog Insensys, and the wavelength changes are calibrated to recover curvature. A
      three-dimensional algorithm is used to generate shape changes during respiration
      that allow the measurement of absolute volume changes at various sections of the
      torso. It is shown that the sensing scheme yields a volumetric error of 6%.
      Comparing the volume data obtained from the spirometer with the volume estimated
      with the synchronous data from the shape-sensing array yielded a correlation
      value 0.86 with a Pearson's correlation coefficient p<0.01.

PMID- 23117811
TI  - Collagen I fiber density increases in lymph node positive breast cancers: pilot
      study.
AB  - Collagen I (Col1) fibers are a major structural component in the extracellular
      matrix of human breast cancers. In a preliminary pilot study, we explored the
      link between Col1 fiber density in primary human breast cancers and the
      occurrence of lymph node metastasis. Col1 fibers were detected by second harmonic
      generation (SHG) microscopy in primary human breast cancers from patients
      presenting with lymph node metastasis (LN+) versus those without lymph node
      metastasis (LN-). Col1 fiber density, which was quantified using our in-house SHG
      image analysis software, was significantly higher in the primary human breast
      cancers of LN+ (fiber volume=29.22%+/-4.72%, inter-fiber distance=2.25+/-0.45 
      MUm) versus LN- (fiber volume=20.33%+/-5.56%, inter-fiber distance=2.88+/-1.07 
      MUm) patients. Texture analysis by evaluating the co-occurrence matrix and the
      Fourier transform of the Col1 fibers proved to be significantly different for the
      parameters of co-relation and energy, as well as aspect ratio and eccentricity,
      for LN+ versus LN- cases. We also demonstrated that tissue fixation and paraffin
      embedding had negligible effect on SHG Col1 fiber detection and quantification.
      High Col1 fiber density in primary breast tumors is associated with breast cancer
      metastasis and may serve as an imaging biomarker of metastasis.

PMID- 23117813
TI  - Temporal and spatial temperature distribution in the glabrous skin of rats
      induced by short-pulse CO2 laser.
AB  - Pain is a natural alarm that aids the body in avoiding potential danger and can
      also present as an important indicator in clinics. Infrared laser-evoked
      potentials can be used as an objective index to evaluate nociception. In animal
      studies, a short-pulse laser is crucial because it completes the stimulation
      before escape behavior. The objective of the present study was to obtain the
      temporal and spatial temperature distributions in the skin caused by the
      irradiation of a short-pulse laser. A fast speed infrared camera was used to
      measure the surface temperature caused by a CO2 laser of different durations (25
      and 35 ms) and power. The measured results were subsequently implemented with a
      three-layer finite element model to predict the subsurface temperature. We found
      that stratum corneum was crucial in the modeling of fast temperature response,
      and escape behaviors correlated with predictions of temperature at subsurface.
      Results indicated that the onset latency and duration of activated nociceptors
      must be carefully considered when interpreting physiological responses evoked by
      infrared irradiation.

PMID- 23117814
TI  - Detection of cerebral autoregulation by near-infrared spectroscopy in neonates:
      performance analysis of measurement methods.
AB  - Cerebral Autoregulation, in clinical practice, is assessed by means of
      correlation or coherence analysis between mean arterial blood pressure (MABP) and
      cerebral blood flow (CBF). However, even though there is evidence linking
      cerebral autoregulation assessment with clinical outcome in preterm infants,
      available methods lack precision for clinical use. Classical methods, used for
      cerebral autoregulation, are influenced by the choice of parameters such as the
      length of the epoch under analysis and the choice of suitable frequency bands.
      The influence of these parameters, in the derived measurements for cerebral
      autoregulation, has not yet been evaluated. In this study, cerebral
      autoregulation was assessed using correlation, coherence, a modified version of
      coherence and transfer function gain, and phase. The influence of the extra
      parameters on the final scores was evaluated by means of sensitivity analysis.
      The methods were applied to a database of 18 neonates with measurements of MABP
      and tissue oxygenation index (TOI). TOI reflects changes in CBF and was measured
      by means of near-infrared spectroscopy.

PMID- 23117815
TI  - An atherogenic diet decreases liver FXR gene expression and causes severe hepatic
      steatosis and hepatic cholesterol accumulation: effect of endurance training.
AB  - PURPOSE: The aim of this study was to determine the effects of an atherogenic
      diet (AD; 40 % lipid, 1.25 % cholesterol, kcal) on triglyceride (TAG) and
      cholesterol accumulation in liver and on gene expression of liver X receptor
      (LXR) and farnesoid X receptor (FXR) and their target genes and to observe if
      these responses are affected by endurance training. METHODS: Sprague-Dawley rats
      (n = 32) were divided into two groups and randomly assigned to an AD or a
      standard diet (SD) for 7 weeks. Half of the rats in each group were assigned to
      an exercise training program for 5 days/week. RESULTS: The AD resulted in a large
      (P < 0.01) accumulation in liver TAG (4*) along with elevated liver and plasma
      cholesterol without any gain in peripheral fat mass. The liver TAG and
      cholesterol accumulations were associated with an important reduction (P < 0.01;
      60 %) in FXR, but no change in LXR transcripts. Accompanying the reduction in FXR
      gene expression, we found an increase (P < 0.001) in SREBP-1c and a decrease (P <
      0.01) in MTP mRNAs suggesting an increased lipogenesis and a reduced VLDL
      production, respectively. The AD was also associated with lower HMG-CoA-r,
      squalene synthase, and ABCG8 transcripts (P < 0.001). In the intestine, exercise
      training resulted in higher NPC1L1, ABCG5, and ABCG8 in SD-fed animals, while all
      these increases were suppressed under the AD feeding. CONCLUSIONS: It is
      concluded that dietary cholesterol favors liver TAG and cholesterol accumulations
      associated with an important reduction in FXR transcripts.

PMID- 23117817
TI  - What do people in forensic secure and community settings think of their
      personality disorder diagnosis? A qualitative study.
AB  - PURPOSE: The aim of this study was to explore the experience of having a
      personality disorder diagnosis within the context of forensic secure and
      community services. METHODS: We used an interpretative phenomenological analysis
      to analyse interviews with 10 service users purposively recruited from services
      in South London. RESULTS: Participants described two facets of their lived
      experience: (1) the way they see themselves now, in light of their offending and
      social background and (2) the pejorative nature of the personality disorder
      label, its relationship to mental illness and their need to distance themselves
      from it. CONCLUSIONS: Having a forensic identity affects participants'
      perceptions of their diagnosis and its treatment as well as their views about
      themselves.

PMID- 23117816
TI  - Differences in views of schizophrenia during medical education: a comparative
      study of 1st versus 5th-6th year Italian medical students.
AB  - PURPOSE: This study explored medical students' causal explanations and views of
      schizophrenia, and whether they changed during medical education. METHOD: The
      survey was carried out on medical students of the Second University of Naples,
      Italy, who attended their first-year and their fifth- or sixth-year of lessons.
      The 381 who accepted were asked to read a case-vignette describing a person who
      met the ICD-10 criteria for schizophrenia and then fill in the Opinions on mental
      illness Questionnaire. RESULTS: The most frequently cited causes were
      psychological traumas (60%) and stress (56%), followed by misuse of street drugs
      (47%), and heredity (42%). 28% of students stated that persons with the disorder
      could be well again, and 28% that they were unpredictable. Labeling the case as
      "schizophrenia" and naming heredity among the causes were associated with
      pessimism about recovery and higher perception of social distance. First-year
      students more frequently reported psychological traumas among the causes (76 vs.
      45%), and less frequently heredity (35 vs. 81%) and stress (42 vs. 69%), and they
      perceived less social distance from the "schizophrenics" than fifth/sixth-year
      students. In particular, 18% percent of first-year versus 38% of fifth/sixth-year
      students believed that these persons were kept at a distance by the other, and 45
      versus 57% felt frightened by persons with the condition. CONCLUSIONS: These
      results indicate a need to include education on stigma and recovery in
      schizophrenia in the training of medical students.

PMID- 23117818
TI  - Ets1 and Elk1 transcription factors regulate cancerous inhibitor of protein
      phosphatase 2A expression in cervical and endometrial carcinoma cells.
AB  - Cancerous inhibitor of protein phosphatase 2A (CIP2A) has been identified as a
      proto-oncogene that is overexpressed in various types of human cancers. CIP2A
      acts by inhibiting protein phosphatase 2A-dependent destabilization of c-Myc,
      resulting in increased cell proliferation. Here, we have characterized the
      proximal promoter region of the human CIP2A gene in cervical, endometrial and
      liver carcinoma cells. The 5' flanking minimal proximal promoter of the CIP2A
      gene consists of putative binding sites for Ets1 and Elk1 in forward and reverse
      orientations. Here, we show that Ets1 and Elk1 binding is essential for CIP2A
      basal expression in several urogenital cancer cell lines. Interestingly, both
      Ets1 and Elk1 are required together for CIP2A expression, as siRNA knockdown of
      Ets1 and Elk1 together decreased CIP2A gene transcription, whereas knockdown of
      Ets1 or Elk1 alone had no effect. Moreover, ectopic expression of Ets1 and Elk1
      together increased CIP2A expression. To gain physiological significance of the
      Ets1 and Elk1 regulation we observed, a panel of matched human cervical carcinoma
      samples was analyzed for the expression of CIP2A and Ets1 and/or Elk1. We found a
      direct correlation between the levels of CIP2A and the levels of Ets1 and Elk1.
      Our results suggest that the binding of Ets1 and Elk1 together to the proximal
      CIP2A promoter is absolutely required for CIP2A expression in cervical,
      endometrial and liver carcinoma cell lines. Thus, different factors regulate
      CIP2A expression in a cell-type specific manner. As previous work has shown a
      requirement for only Ets1 in prostate and gastric carcinomas, our results now
      indicate that CIP2A regulation is more complex than previously determined.

PMID- 23117819
TI  - A sticky situation: untangling the transcriptional network controlling biofilm
      development in Candida albicans.
AB  - Candida albicans is a commensal microorganism of the human microbiome; it is also
      the most prevalent fungal pathogen of humans. Many infections caused by C.
      albicans are a direct consequence of its proclivity to form biofilms--resilient,
      surface-associated communities of cells where individual cells acquire
      specialized properties that are distinct from those observed in suspension
      cultures. We recently identified the transcriptional network that orchestrates
      the formation of biofilms in C. albicans. These results set the stage for
      understanding how biofilms are formed and, once formed, how the specialized
      properties of biofilms are elaborated. This information will provide new insight
      for understanding biofilms in more detail and may lead to improvements in
      preventing and treating biofilm-based infections in the future.

PMID- 23117820
TI  - Histone H3 lysine 4 methylation revisited.
AB  - Since its discovery more than a decade ago, H3K4 methylation has become
      synonymous with transcription. We only now have begun to realize that the
      distinct states of H3K4 methylation have unique distributions and specialized
      roles in other chromatin-related processes. Here, I discuss recent findings
      addressing their regulation and functions.

PMID- 23117821
TI  - Akt1, EMSY, BRCA2 and type I IFN signaling: a novel arm of the IFN response.
AB  - Interferon-stimulated transcription is thought to occur mainly through the action
      of the JAK/STAT pathway. However, recent findings revealed an additional PI3K/Akt
      dependent pathway, which contributes to the induction of a set of interferon
      stimulated genes (ISGs) through the regulation of the transcriptional repressor
      EMSY.

PMID- 23117822
TI  - A new way to start: nanoRNA-mediated priming of transcription initiation.
AB  - A recent study provides evidence that RNA polymerase uses 2- to ~4-nt RNAs,
      species termed "nanoRNAs," to prime transcription initiation in Escherichia coli.
      Priming of transcription initiation with nanoRNAs represents a previously
      undocumented component of transcription start site selection and gene expression.

PMID- 23117823
TI  - Core promoter-selective coregulators of transcription by RNA polymerase II.
AB  - The core promoter of eukaryotic genes is structurally and functionally diverse
      and contributes to the combinatorial control of gene-specific transcription.
      Recent findings identifying specific coactivators and architectural proteins as
      core promoter-specific basal cofactors for RNA polymerase II suggest possible
      mechanisms for the core promoter selectivity of certain regulators and enhancers.

PMID- 23117824
TI  - Tendency towards stigmatization of families of a person with autistic spectrum
      disorders.
AB  - BACKGROUND: Family members experience stigma via their connection with the
      affected member. Family stigma contains stereotypes of blame, shame and
      contamination. AIM: To establish the tendency towards stigmatization of family
      members of a person with autistic spectrum disorders (ASD) by a sample of the
      general public of Belgrade. METHODS: The sample encompassed 181 participants, of
      various ages and levels of education, and of different, self-assessed levels of
      knowledge about autism. The structure of stigmatization of family members of a
      person with ASD was explored applying the Family Stigma Questionnaire (FSQ) and
      the Level of Familiarity Questionnaire (LFQ). RESULTS: Analysis of the obtained
      results established that scores indicating the tendency towards stigmatization
      were most pronounced for variables connected to blame for deterioration of the
      condition of the person with autism, contamination of the individual family
      members by the condition, and to feeling pity for family members of a person with
      ASD. Statistically significant differences were established when the FSQ scores
      stigmatizing parents and siblings were compared. Significant differences in
      stigmatizing stereotypes were established according to gender and level of
      education, and according to the self-assessment of knowledge about autism and the
      level of previous contact to persons with mental disorders. CONCLUSION: Anti
      stigma programmes are important especially bearing in mind that participants who
      self-evaluated as having the least knowledge about ASD demonstrated the highest
      tendency towards stigmatizing the parents of a person suffering from ASD, and
      those of lower education demonstrated the highest tendency towards stigmatizing
      the family members.

PMID- 23117825
TI  - Social characteristics of psychological distress in disadvantaged areas of
      Berlin.
AB  - PURPOSE: Living in disadvantaged urban areas is associated with poor mental
      health. The purpose of this study was to assess which social characteristics were
      associated with psychological distress within a disadvantaged, multi-ethnic
      neighbourhood of Berlin. METHODS: The study was conducted in an area of Berlin
      with the highest rates of unemployment and highest density of migrants. A total
      of 143 participants aged 18-57 years were included from a random sample. The
      social characteristics educational level, employment status, marital status,
      living alone, per-capita income and background of migration were collected.
      Psychological distress was assessed using the General Health Questionnaire GHQ
      28; scores >= 5 indicated psychological distress corresponding to psychiatric
      caseness. RESULTS: Psychological distress was found in 40.6% (n = 58) of the
      sample. Psychological distress was associated with younger age (OR = 0.95, 95% CI
      = 0.92-0.98, p = .004), female gender (OR = 3.51, 95% CI = 1.55-7.92, p = .003)
      and living alone (OR = 3.88, 95% CI = 1.58-9.52, p = .003), but not with
      background of migration, low educational level or with unemployment. CONCLUSIONS:
      Young age and female gender may predispose for psychological distress in
      disadvantaged areas. Living alone could be a social indicator of poor mental
      health within disadvantaged urban areas. The directionality of the association is
      unclear. BACKGROUND: of migration, low income and educational level do not seem
      to be associated with poor mental health within those areas.

PMID- 23117826
TI  - Morphological and molecular characterization of Explanatum explanatum from cattle
      and buffaloes in Myanmar.
AB  - A robust molecular marker is needed for discrimination of amphistome species,
      because identification based on morphology alone requires specialized knowledge
      and techniques. In this study, we performed morphological and molecular
      characterization of Explanatum explanatum, a species that causes severe liver
      damage in definitive host species. Fifty-five adult amphistomes were collected
      from cattle and water buffaloes in Myanmar. Eighteen of the amphistomes,
      arbitrarily chosen, were morphologically identified as E. explanatum using
      sagittal sections. All of the 55 amphistome isolates had identical second
      internal transcribed spacer (ITS2) of ribosomal DNA sequences; these sequences
      differed at 7 nucleotide sites from those of the closest species, Paramphistomum
      leydeni. Our data indicate that the ITS2 sequence could be a useful molecular
      marker for epidemiological studies on E. explanatum.

PMID- 23117827
TI  - Canonical Wnt signaling pathway plays an essential role in N-methyl-N-nitrosurea
      induced gastric tumorigenesis of mice.
AB  - Deregulated Wnt signaling pathway is implicated in many hereditary diseases and
      tumorigenesis including colorectal cancer, hepatocellular carcinoma and gastric
      cancer. In this study, to assess the relationship between chemically induced
      gastric tumor and canonical Wnt signaling pathway in genetically intact mice,
      histopathological and quantitative mRNA analyses were performed in C57BL/6J mice
      given drinking water containing N-methyl- N-nitrosurea (MNU). 60.5% of gastric
      adenoma and 27.9% of adenocarcinoma were observed 48 weeks after first
      administration. Also, in immunohistochemical analysis, aberrant expressions of
      phospho-GSK-3beta, beta-catenin, cyclin D1, c-Myc, osteopontin and COX-2 were
      found. In double immunofluorescent-antibody stains, beta-catenin accumulation was
      colocalized with other proteins. mRNA levels of cyclin D1, c-myc and COX-2 were
      relatively higher in adenocarcinoma. Altogether, canonical Wnt pathway was highly
      involved in MNU induced gastric neoplasia of C57BL/6J mice, and it could be a
      considerably suitable system for the study to examine the linkage between gastric
      tumorigenesis and the canonical Wnt pathway.

PMID- 23117828
TI  - Increased von Willebrand Factor to ADAMTS13 ratio as a predictor of thrombotic
      complications following a major hepatectomy.
AB  - OBJECTIVE: To investigate the association between changes in
      procoagulant/fibrinolytic factors and thrombotic complications following a major
      hepatectomy. Little information is available regarding the changes in
      procoagulant/fibrinolytic factors (such as the von Willebrand factor [vWF] and a
      disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13
      [ADAMTS13]), following a major hepatectomy. DESIGN: Patients who underwent a
      major hepatectomy from 2010 to 2011 were enrolled. Patients who underwent a
      pancreatoduodenectomy (PD) during the same period were also observed as controls,
      for whom operation time and amount of intraoperative blood loss were comparable
      to those of the patients who underwent a major hepatectomy. Blood samples were
      prospectively collected to measure various procoagulant/fibrinolytic factors,
      including vWF and ADAMTS13. SETTING: Nagoya University Hospital, Japan. PATIENTS:
      A total of 50 patients who underwent a major hepatectomy and a total of 23
      patients who underwent a PD. RESULTS: The levels of vWF in the patients who
      underwent a major hepatectomy increased from before the operation to the seventh
      postoperative day and were significantly higher than those observed in the
      patients who underwent a PD. The ADAMTS13 activity in the patients who underwent
      a major hepatectomy gradually decreased throughout the first 14 postoperative
      days. In contrast, ADAMTS13 activity in the patients who underwent a PD returned
      to nearly normal levels within 2 weeks. Three patients who underwent a major
      hepatectomy had clinically significant thrombotic complications within the first
      2 weeks after surgery; however, none of the patients who underwent a PD had
      thrombotic complications. The vWF to ADAMTS13 ratios of the 3 patients who
      experienced thrombotic complications were extremely high even before the
      occurrence of complications. No other procoagulant/fibrinolytic factors showed a
      marked association with thrombotic events. The vWF to ADAMTS13 ratio was
      significantly correlated with the estimated liver remnant volume (P < .001) but
      not with other preoperative or intraoperative factors. CONCLUSIONS: The vWF to
      ADAMTS13 ratio may be a potentially useful marker in predicting thrombotic
      complications following a major hepatectomy.

PMID- 23117829
TI  - ADAMTS13: The surgeon's friend or foe.

PMID- 23117830
TI  - Initial experience with hyperthermic intraperitoneal chemotherapy.
AB  - BACKGROUND: Until 2004, we treated peritoneal carcinomatosis with cytoreductive
      surgery accompanied by perioperative systemic chemotherapy. From October 2004, we
      decided to initiate a hyperthermic intraperitoneal chemotherapy (HIPEC) program
      for this condition. OBJECTIVE: To determine the effect of HIPEC on postoperative
      outcomes at a single institution performing a high volume of cancer operations.
      METHOD: Sixty consecutive patients underwent cytoreductive surgery plus HIPEC
      (oxaliplatin; 460 mg/m2 in 2 L/m2) from October 1, 2004, through December 31,
      2010. Usual perioperative factors were studied for 3 groups of patients who
      underwent HIPEC: 0 to 20 HIPEC procedures (period 1), 21 to 40 HIPEC procedures
      (period 2), and 41 to 60 HIPEC procedures (period 3). RESULTS: The mean
      peritoneal carcinomatosis index was 9.6, the mean duration of surgery was 410.7
      minutes, and the mean blood loss was 450.2 mL/L. Mortality and morbidity were 0%
      and 33%, respectively. Grade III/IV morbidity (P = .02), transfusion (P < .01),
      and reintervention rate (P = .04) significantly decreased during the 3 periods.
      No difference was seen between the 3 periods with regard to mean peritoneal
      carcinomatosis index, operative duration, blood loss, mortality, overall
      morbidity, length of hospital stay, and readmission. The overall 1-, 3-, and 5
      year survival rates of 26 patients with peritoneal carcinomatosis originating
      from colorectal cancer were 100%, 51%, and 37%, respectively. The overall median
      survival was 39 months. CONCLUSIONS: We observed a significant reduction of grade
      III/IV morbidity, perioperative transfusion, and reintervention rate after 20
      procedures. The introduction of the HIPEC program was successful because of the
      surgical team's prior experience in cytoreductive and cancer operations.

PMID- 23117831
TI  - The heat of the matter.

PMID- 23117833
TI  - Work-home conflicts have a substantial impact on career decisions that affect the
      adequacy of the surgical workforce.
AB  - OBJECTIVE: To evaluate factors associated with work-home conflicts (W-HCs) of US
      surgeons and their potential personal and professional consequences. DESIGN:
      Cross-sectional study. PARTICIPANTS: Members of the American College of Surgeons.
      MAIN OUTCOME MEASURES: Burnout, depression, quality of life, alcohol use, career
      satisfaction, and career decisions (ie, reduce work hours or leave current
      practice). RESULTS: Of 7197 participating surgeons, 3754 (52.5%) had experienced
      a W-HC in the previous 3 weeks. On multivariate analysis, hours worked per week,
      having children, sex, and work location (Veterans Administration or academic
      center) were independently associated with an increased risk for W-HC (all P <
      .01), while some factors (increased age and subspecialty field) reduced the risk.
      Surgeons with a recent W-HC were more likely to have symptoms of burnout (36.9%
      vs 17.1%; P < .001), depression (50.9% vs 28.1%; P < .001), alcohol
      abuse/dependency (17.2% vs 14.4%; P = .003), and were less likely to recommend
      surgery as a career option to their children (46.0% vs 54.4%; P < .001). Work
      home conflicts were also independently associated with surgeons reporting a
      moderate or higher likelihood of planning to reduce clinical work hours (odds
      ratio, 1.769) and leave their current practice in the next 24 months for a reason
      other than retirement (odds ratio, 1.706) after controlling for other personal
      and professional factors. CONCLUSIONS: Integrating personal and professional
      lives is a substantial challenge for US surgeons. Conflict in this balance
      appears to be a major factor in their decision to reduce work hours and/or move
      to a new practice, with potential substantive manpower implications for the
      surgical workforce.

PMID- 23117834
TI  - Training future surgeons for management roles: the resident-surgeon-manager
      conference.
AB  - OBJECTIVE To demonstrate that senior surgical residents would benefit from
      focused training by professionals with management expertise. Although managerial
      skills are recognized as necessary for the successful establishment of a surgical
      practice, they are not often emphasized in traditional surgical residency
      curricula. DESIGN Senior residents from all surgical subspecialties at McGill
      University were invited to participate in a 1-day management seminar. Precourse
      questionnaires aimed at evaluating the residents' perceptions of their own
      managerial knowledge and preparedness were circulated. The seminar was then given
      in the form of interactive lectures and case-based discussions. The
      questionnaires were readministered at the end of the course, along with an
      evaluation form. Precourse and postcourse data were compared using the Freeman
      Halton extension of the Fisher exact test to determine statistical significance
      (P < .05). SETTING  McGill University Health Centre in Montreal, Quebec, Canada.
      PARTICIPANTS A total of 43 senior residents. RESULTS Before the course, the
      majority of residents (27 of 43 [63%]) thought that management instruction only
      happened "from time to time" in their respective programs. After the course, 15
      residents (35%) felt that management topics were "well addressed," and 19 (44%)
      felt that management topics have been "very well addressed" (P < .01). Residents
      noted a significant improvement in their ability to perform the following skills
      after the course: giving feedback, delegating duties, coping with stress,
      effective learning, and effective teaching. On the ensemble of all managerial
      skills combined, 26 residents (60%) rated their performance as "good" or
      "excellent" after the course vs only 21 (49%) before the course (P = .02).
      Residents also noted a statistically significant improvement in their ability to
      perform the managerial duties necessary for the establishment of a surgical
      practice. CONCLUSIONS Surgical residency programs have the responsibility of
      preparing their residents for leadership and managerial roles in their future
      careers. An annual seminar serves as a starting point that could be built on for
      incorporating formal management training in surgical residency curricula.

PMID- 23117835
TI  - Developing leaders in surgery.

PMID- 23117832
TI  - Clinical outcome in relation to timing of surgery in chronic pancreatitis: a
      nomogram to predict pain relief.
AB  - OBJECTIVE: To evaluate the effect of timing of surgery on the long-term clinical
      outcome of surgery in chronic pancreatitis (CP). DESIGN: Cohort study with long
      term follow-up. SETTING: Five specialized academic centers. PATIENTS: Patients
      with CP treated surgically for pain. INTERVENTIONS: Pancreatic resection and
      drainage procedures for pain relief. MAIN OUTCOME MEASURES: Pain relief (pain
      visual analogue score <=4), pancreatic function, and quality of life. RESULTS: We
      included 266 patients with median follow-up of 62 months (interquartile range, 31
      112). Results were presented as odds ratios (ORs)with 95% confidence intervals
      after correction for bias using bootstrap-corrected analysis. Pain relief was
      achieved in 149 patients (58%). Surgery within 3 years of symptoms was
      independently associated with more pain relief (OR, 1.8; 95% CI, 1.0-3.4; P =
      .03) and less endocrine pancreatic insufficiency (OR, 0.57; 95% CI, 0.33-0.96; P
      = .04). More pain relief was also observed in patients not taking opioids
      preoperatively (OR, 2.1; 95% CI, 1.2-4.0; P = .006) and who had 5 or fewer
      endoscopic treatments prior to surgery (OR, 2.5; 95% CI, 1.1-6.3; P = .04). The
      probability of achieving pain relief varied between 23% and 75%, depending on
      these risk factors. CONCLUSIONS: The timing of surgery is an important risk
      factor for clinical outcome in CP. Surgery may need to be considered at an
      earlier phase than it is now, preferably within 3 years of symptomatic CP.
      Likelihood of postoperative pain relief can be calculated on an individual basis
      using the presented nomogram.

PMID- 23117836
TI  - Dietary supplementation with monosodium glutamate is safe and improves growth
      performance in postweaning pigs.
AB  - Dietary intake of glutamate by postweaning pigs is markedly reduced due to low
      feed consumption. This study was conducted to determine the safety and efficacy
      of dietary supplementation with monosodium glutamate (MSG) in postweaning pigs.
      Piglets were weaned at 21 days of age to a corn and soybean meal-based diet
      supplemented with 0, 0.5, 1, 2, and 4 % MSG (n = 25/group). MSG was added to the
      basal diet at the expense of cornstarch. At 42 days of age (21 days after
      weaning), blood samples (10 mL) were obtained from the jugular vein of 25
      pigs/group at 1 and 4 h after feeding for hematological and clinical chemistry
      tests; thereafter, pigs (n = 6/group) were euthanized to obtain tissues for
      histopathological examinations. Feed intake was not affected by dietary
      supplementation with 0-2 % MSG and was 15 % lower in pigs supplemented with 4 %
      MSG compared with the 0 % MSG group. Compared with the control, dietary
      supplementation with 1, 2 and 4 % MSG dose-dependently increased plasma
      concentrations of glutamate, glutamine, and other amino acids (including lysine,
      methionine, phenylalanine and leucine), daily weight gain, and feed efficiency in
      postweaning pigs. At day 7 postweaning, dietary supplementation with 1-4 % MSG
      also increased jejunal villus height, DNA content, and antioxidative capacity.
      The MSG supplementation dose-dependently reduced the incidence of diarrhea during
      the first week after weaning. All variables in standard hematology and clinical
      chemistry tests, as well as gross and microscopic structures, did not differ
      among the five groups of pigs. These results indicate that dietary
      supplementation with up to 4 % MSG is safe and improves growth performance in
      postweaning pigs.

PMID- 23117837
TI  - Selective PDE5A inhibition with sildenafil rescues left ventricular dysfunction,
      inflammatory immune response and cardiac remodeling in angiotensin II-induced
      heart failure in vivo.
AB  - Sildenafil inhibits cyclic GMP-specific phosphodiesterase type-5A (PDE5A) and can
      prevent cardiac hypertrophy and left ventricular (LV) dysfunction in mice
      subjected to severe pressure-overload. The pathophysiological role of sildenafil
      in adverse remodeling in the hypertensive heart after chronic renin-angiotensin
      aldosterone system stimulation is unknown. Therefore, we studied the efficacy of
      the PDE5A inhibitor sildenafil for treating advanced cardiac hypertrophy and LV
      remodeling due to angiotensin (Ang)II-induced heart failure (HF) in vivo.
      C57BL6/J mice were subjected to AngII-induced cardiac hypertrophy for 3 weeks and
      cardiac dysfunction, cardiac inflammatory stress response, adverse remodeling as
      well as apoptosis were documented. Mice were subsequently treated with sildenafil
      (100 mg/kg/day) or placebo with delay of 5 days for treating AngII infusion
      induced adverse events. Compared to controls, AngII infusion resulted in impaired
      systolic (dP/dt (max) -46 %, SV -16 %, SW -43 %, E (a) +51 %, EF -37 %, CO -36 %;
      p < 0.05) and diastolic (dP/dt (min) -36 %, LV end diastolic pressure +73 %, Tau
      +21 %, stiffness constant beta +74 %; p < 0.05) LV function. This was associated
      with a significant increase in cardiac hypertrophy and fibrosis. Increased
      inflammatory response was also indicated by an increase in immune cell
      infiltration and apoptosis. Treatment with sildenafil led to a significant
      improvement in systolic and diastolic LV performance. This effect was associated
      with less LV hypertrophy, remodeling, cardiac inflammation and apoptosis. PDE5A
      inhibition with sildenafil may provide a new treatment strategy for cardiac
      hypertrophy and adverse remodeling in the hypertensive heart.

PMID- 23117838
TI  - Visualizing bacteria in nematodes using fluorescent microscopy.
AB  - Symbioses, the living together of two or more organisms, are widespread
      throughout all kingdoms of life. As two of the most ubiquitous organisms on
      earth, nematodes and bacteria form a wide array of symbiotic associations that
      range from beneficial to pathogenic (1-3). One such association is the mutually
      beneficial relationship between Xenorhabdus bacteria and Steinernema nematodes,
      which has emerged as a model system of symbiosis (4). Steinernema nematodes are
      entomopathogenic, using their bacterial symbiont to kill insects (5). For
      transmission between insect hosts, the bacteria colonize the intestine of the
      nematode's infective juvenile stage (6-8). Recently, several other nematode
      species have been shown to utilize bacteria to kill insects (9-13), and
      investigations have begun examining the interactions between the nematodes and
      bacteria in these systems (9). We describe a method for visualization of a
      bacterial symbiont within or on a nematode host, taking advantage of the optical
      transparency of nematodes when viewed by microscopy. The bacteria are engineered
      to express a fluorescent protein, allowing their visualization by fluorescence
      microscopy. Many plasmids are available that carry genes encoding proteins that
      fluoresce at different wavelengths (i.e. green or red), and conjugation of
      plasmids from a donor Escherichia coli strain into a recipient bacterial symbiont
      is successful for a broad range of bacteria. The methods described were developed
      to investigate the association between Steinernema carpocapsae and Xenorhabdus
      nematophila (14). Similar methods have been used to investigate other nematode
      bacterium associations (9)   (,)   (15-18)and the approach therefore is generally
      applicable. The method allows characterization of bacterial presence and
      localization within nematodes at different stages of development, providing
      insights into the nature of the association and the process of colonization (14) 
      (,)   (16)   (,)   (19). Microscopic analysis reveals both colonization
      frequency within a population and localization of bacteria to host tissues (14)  
      (,)   (16)   (,)   (19-21). This is an advantage over other methods of monitoring
      bacteria within nematode populations, such as sonication (22)or grinding (23),
      which can provide average levels of colonization, but may not, for example,
      discriminate populations with a high frequency of low symbiont loads from
      populations with a low frequency of high symbiont loads. Discriminating the
      frequency and load of colonizing bacteria can be especially important when
      screening or characterizing bacterial mutants for colonization phenotypes (21)  
      (,)   (24). Indeed, fluorescence microscopy has been used in high throughput
      screening of bacterial mutants for defects in colonization (17)   (,)   (18), and
      is less laborious than other methods, including sonication (22)   (,)   (25
      27)and individual nematode dissection (28)   (,)   (29).

PMID- 23117839
TI  - Detection limits of DNA copy number alterations in heterogeneous cell
      populations.
AB  - BACKGROUND: Array Comparative Genomic Hybridization (aCGH) is a widely used
      technique to assess chromosomal copy number alterations. Chromosomal content,
      however, is often not uniform throughout cell populations. Here we evaluated to
      what extent aCGH can detect DNA copy number alterations in heterogeneous cell
      populations. A systematic evaluation is currently lacking, despite its importance
      in diagnostics and research. The detection limits reported are a compound of
      analytical software and laboratory techniques and do not account for the number
      of probes in relation to sample homogeneity. METHODS: Detection limits were
      explored with DNA isolated from a patient with intellectual disability (ID) and
      from tumor cell line BT474. Both were diluted with increasing amounts of normal
      DNA to simulate different levels of cellularity. Samples were hybridized on
      microarrays containing 180,880 oligonucleotides evenly distributed over the
      genome (spacing ~17 kb). RESULTS: Single copy number alterations, represented by
      down to 249 probes (4 Mb) and present in 10 % of a cell population, could be
      detected. Alterations encompassing as few as 14 probes (~238 Kb) could also be
      detected, but for this a 35 % mosaic level was required. CONCLUSIONS: DNA copy
      number alterations can be detected in cell populations containing 10 % abnormal
      cells. Detection of sub-megabase alterations requires a higher percentage of
      abnormal cells or microarrays with a higher probe density.

PMID- 23117840
TI  - Simultaneous determination of serum galectin-3 and -4 levels detects metastases
      in colorectal cancer patients.
AB  - BACKGROUND: Development of effective ways to detect metastases is highly
      desirable for improving the therapeutic strategies and survival of cancer
      patients. Serum levels of galectin-3 and -4, two members of the galactoside
      binding galectin family, have recently been reported to be markedly increased up
      to 31-fold in the bloodstream of colorectal cancer patients and in particular
      those with metastases. RESULTS: We found that simultaneous determination of serum
      galectin-3 and -4 levels in a single assay provides a high specificity and
      sensitivity in distinguishing colorectal cancer patients without metastases from
      those with liver metastases. This result was partly attributed by a reciprocal
      relationship of serum galectin-3 and -4 levels in patients with metastases.
      Higher serum galectin-3/-4 levels at the time of primary tumour removal in
      patients who did not exhibit clinically detectable metastases were associated
      with a trend of a poorer patients' survival in the next 10 years. CONCLUSION:
      Simultaneous determination of serum galectin-3 and -4 levels can potentially be
      used alone or in combination with other assessments to detect colorectal cancer
      metastases.

PMID- 23117841
TI  - The benefits of exercise in Parkinson disease.

PMID- 23117842
TI  - The Lalli and Weber effects and the incidence of acute non-renal adverse
      reactions to contrast media.

PMID- 23117845
TI  - Simultaneous PET/MR imaging of the brain: feasibility of cerebral blood flow
      measurements with FAIR-TrueFISP arterial spin labeling MRI.
AB  - BACKGROUND: Hybrid positron emission tomography/magnetic resonance imaging
      (PET/MRI) with simultaneous data acquisition promises a comprehensive evaluation
      of cerebral pathophysiology on a molecular, anatomical, and functional level.
      Considering the necessary changes to the MR scanner design the feasibility of
      arterial spin labeling (ASL) is unclear. PURPOSE: To evaluate whether cerebral
      blood flow imaging with ASL is feasible using a prototype PET/MRI device.
      MATERIAL AND METHODS: ASL imaging of the brain with Flow-sensitive Alternating
      Inversion Recovery (FAIR) spin preparation and true fast imaging in steady
      precession (TrueFISP) data readout was performed in eight healthy volunteers
      sequentially on a prototype PET/MRI and a stand-alone MR scanner with 128 * 128
      and 192 * 192 matrix sizes. Cerebral blood flow values for gray matter, signal-to
      noise and contrast-to-noise ratios, and relative signal change were compared.
      Additionally, the feasibility of ASL as part of a clinical hybrid PET/MRI
      protocol was demonstrated in five patients with intracerebral tumors. RESULTS:
      Blood flow maps showed good delineation of gray and white matter with no
      discernible artifacts. The mean blood flow values of the eight volunteers on the
      PET/MR system were 51 +/- 9 and 51 +/- 7 mL/100 g/min for the 128 * 128 and 192 *
      192 matrices (stand-alone MR, 57 +/- 2 and 55 +/- 5, not significant). The value
      for signal-to-noise (SNR) was significantly higher for the PET/MRI system using
      the 192 * 192 matrix size (P < 0.01), the relative signal change (deltaS) was
      significantly lower for the 192 * 192 matrix size (P = 0.02). ASL imaging as part
      of a clinical hybrid PET/MRI protocol could successfully be accomplished in all
      patients in diagnostic image quality. CONCLUSION: ASL brain imaging is feasible
      with a prototype hybrid PET/MRI scanner, thus adding to the value of this novel
      imaging technique.

PMID- 23117848
TI  - Central nervous system aspergillosis: a series of 14 cases from a general
      hospital and review of 123 cases from the literature.
AB  - Central nervous system (CNS) aspergillosis is a highly fatal infection. We review
      the clinical presentation, diagnosis, and outcome of this infection and present a
      case series of 14 consecutive patients with CNS aspergillosis admitted to
      Massachusetts General Hospital (MGH) from 2000 to 2011. We also review 123 cases
      reported in the literature during that time. We included only proven CNS
      aspergillosis cases conforming to the European Organization for Research and
      Treatment of Cancer/Mycoses Study Group (EORTC/MSG) definitions of invasive
      fungal infections. In the MGH case series, neutropenia, hematologic malignancies,
      autoimmune diseases requiring steroid treatment, and solid organ transplantation
      were the predominant comorbid conditions. Notably, all MGH patients were
      immunosuppressed, and more than half (n = 8) had a history of previous brain
      injury, unrelated to their index hospitalization. For most MGH patients (11 of
      14), the lung was the primary focus of aspergillosis, while 2 had paranasal sinus
      involvement, and 1 had primary Aspergillus discitis. Among reported cases,
      paranasal sinuses (27.6%) and the lung (26.8%) were the primary foci of
      infection, whereas 22% of those cases had no obvious primary organ involvement.
      Although a selection bias should be considered, especially among published cases,
      our findings suggest that patients who underwent neurosurgery had improved
      survival, with MGH and literature patients having 25% and 28.6% mortality,
      respectively, compared to 100% and 60.4%, respectively, among patients who
      received only medical treatment. Although this was not the case among MGH
      patients, CNS aspergillosis can affect patients without significant immune
      suppression, as indicated by the high number of reported immunocompetent cases.
      In conclusion, mortality among CNS aspergillosis patients remains high, and the
      infection may be more common among patients with previous brain pathology. When
      indicated, neurosurgical procedures may improve prognosis.

PMID- 23117847
TI  - Confirmatory factor analysis of the Work Limitations Questionnaire (WLQ-25) in
      Workers' Compensation Claimants with chronic upper-limb disorders.
AB  - PURPOSE: To examine the factorial validity of the Work Limitations Questionnaire
      (WLQ-25) among workers' compensation claimants with chronic upper-limb disorders.
      METHODS: Attendees of the WSIB Shoulder and Elbow Specialty clinic in Toronto,
      Ontario, Canada, completed a survey that includes the WLQ-25 [4 subscales: time
      management (TM), physical demands (PD), mental-interpersonal (MI), and output
      demands (OD)]. Confirmatory factor analyses (n = 2262) were conducted to evaluate
      and compare alternative 4- and 5-factor WLQ-25 structures [MI subscale intact vs.
      separated into mental demands (MD) and interpersonal demands (IP) subscales].
      Model fit indices, saliency of factor loadings, and convergent/divergent validity
      of latent factors (r = 0.4 - 0.85 expected) were concurrently assessed. RESULTS:
      The 4-factor WLQ-25 showed acceptable model fit after allowing the residuals of a
      pair of PD items to correlate (CFI = 0.924, TLI = 0.915, RMSEA = 0.057, SRMR =
      0.054); however, significantly lower-than-expected correlations between the PD
      factor and all other factors (r = -0.11 - -0.03) were also observed. Model fit
      for the 5-factor WLQ-25 was even more optimal (CFI = 0.934, TLI = 0.925, RMSEA =
      0.053, SRMR = 0.051), with MD and IP factors correlating at r = 0.83.
      CONCLUSIONS: Evidence of factorial validity was demonstrated by the WLQ-25;
      however, users should be attentive of an instrumentation issue that could be
      directly related to the psychometric performance of its PD subscale.

PMID- 23117849
TI  - Clinical outcome after a totally implantable venous access port-related infection
      in cancer patients: a prospective study and review of the literature.
AB  - Morbidity and mortality after a totally implantable venous access port (TIVAP)
      related infection in oncology patients have rarely been studied. We conducted
      this study to assess the incidence and factors associated with the following
      outcome endpoints: severe sepsis or septic shock at presentation, cancellation of
      antineoplastic chemotherapy, and mortality at week 12. We conducted a prospective
      single-center observational study including all adult patients with solid cancer
      who experienced a TIVAP-related infection between February 1, 2009, and October
      31, 2010. Patients were prospectively followed for 12 weeks. Among 1728 patients
      receiving antineoplastic chemotherapy during the inclusion time, 72 had an
      episode of TIVAP-related infection (4.2%) and were included in the study (median
      age, 60 yr; range, 28-85 yr). The incidence of complications was 18% for severe
      sepsis or septic shock (13/72 patients), 30% for definitive cancellation of
      antineoplastic chemotherapy (14/46 patients who still had active treatment), and
      46% for death at week 12 (33/72 patients). Factors associated with severe sepsis
      or septic shock were an elevated C-reactive protein (CRP) level and an infection
      caused by Candida species; 4 of the 13 severe episodes (31%) were due to
      coagulase-negative staphylococci (CoNS). Factors associated with death at week 12
      were a low median Karnofsky score, an elevated Charlson comorbidity index, the
      metastatic evolution of cancer, palliative care, and an elevated CRP level at
      presentation. Hematogenous complications (that is, infective endocarditis, septic
      thrombophlebitis, septic pulmonary emboli, spondylodiscitis, septic arthritis, or
      organ abscesses) were found in 8 patients (11%). In conclusion, patients' overall
      condition (comorbidities and autonomy) and elevated CRP level were associated
      with an unfavorable clinical outcome after a TIVAP-related infection. Candida
      species and CoNS were responsible for severe sepsis or septic shock.

PMID- 23117850
TI  - Natural history of adults with congenitally malformed aortic valves (unicuspid or
      bicuspid).
AB  - Appreciation of the frequency of the congenitally malformed aortic valve has come
      about during the last 50 years, a period during which aortic valve replacement
      became a predictably successful operation. Study of patients at necropsy with
      either a congenitally unicuspid (1 true commissure) or bicuspid (2 true
      commissures) valve in whom no aortic valve operation has been performed has not
      been conducted during these 50 years, to our knowledge. We studied 218 patients
      at necropsy with congenitally malformed aortic valves: 28 (13%) had a unicuspid
      valve and 190 (87%), a bicuspid valve. Their ages at death ranged from 21 to 89
      years (mean, 55 yr), and 80% were men. Of the 218 adults, the aortic valve
      functioned normally during life in 54 (25%) and abnormally in 164 (75%): aortic
      stenosis in 142 (65%), pure aortic regurgitation without superimposed infective
      endocarditis (IE) in 2 (1%), and IE superimposed on a previously normally
      functioning aortic valve in 20 (9%). IE occurred in a total of 31 (14%) of the
      218 patients: involving a previously normally functioning valve in 20 (65%) and a
      previously stenotic valve in 11 (35%). Of the 218 patients, at least 141 (65%)
      died as a consequence of aortic valve disease (124 patients) or ascending aortic
      tears with or without dissection (17 patients). An estimated 1% of the
      population, maybe higher in men, has a congenitally malformed aortic valve. Data
      from this study suggest that about 75% of them will develop a major complication.
      Conversely, and encouragingly, about 25% will go through life without a
      complication.

PMID- 23117851
TI  - Nonalcoholic fatty liver disease in lean individuals in the United States.
AB  - The presence of hepatic steatosis in individuals without a known cause of chronic
      liver disease, including excessive alcohol consumption, is the hallmark of
      nonalcoholic fatty liver disease (NAFLD). Although NAFLD is usually associated
      with obesity, nonobese patients can also present with NAFLD ("lean NAFLD"). Our
      objective was to determine factors independently associated with lean NAFLD in
      the United States population. For this purpose, we used data from National Health
      and Nutrition Examination Survey III (NHANES III) conducted between 1988 and 1994
      with available hepatic ultrasound, clinico-demographic, and laboratory data.
      NAFLD was defined as the presence of moderate-severe hepatic steatosis (by
      ultrasound), the absence of excessive alcohol use (>20 g/d in men and 10 g/d in
      women), hepatitis B surface antigen(-), and hepatitis C antibody(-). Nonalcoholic
      steatohepatitis (NASH) was defined as having moderate-severe steatosis and
      elevated aminotransferases in the presence of type 2 diabetes or insulin
      resistance (IR). Logistic regression was used to identify independent predictors
      of lean NAFLD. As a result, of the 11,613 participants included in the study,
      2185 (18.77% +/- 0.76%) had NAFLD; of these, 307 (11.78% +/- 1.03%) had NASH.
      Multivariate analysis showed that lean NAFLD was independently associated with
      younger age, female sex, and a decreased likelihood of having IR and
      hypercholesterolemia (p values < 0.05). Additionally, multivariate analysis
      showed that NASH was independently associated with being Hispanic, having a
      younger age, and having components of metabolic syndrome such as hypertension (p
      values < 0.05). Therefore, we conclude that lean individuals with NAFLD have a
      different clinical profile than overweight-obese individuals with NAFLD.
      Furthermore, patients with NASH are commonly Hispanic and have components of
      metabolic syndrome.

PMID- 23117852
TI  - Evaluation of IGF1R and phosphorylated IGF1R as targets in HER2-positive breast
      cancer cell lines and tumours.
AB  - Insulin-like growth factor-1 receptor (IGF1R) signalling is implicated in
      resistance to trastuzumab. However, the benefit of co-targeting HER2 and IGF1R
      has not been extensively studied, and the relationship between activated IGF1R
      and clinical response to trastuzumab has not been reported. This study aimed to
      evaluate the combination of trastuzumab with IGF1R tyrosine kinase inhibitors
      (TKIs) in a panel of HER2-positive breast cancer cell lines, and to examine the
      relationship between IGF1R expression and activation and response to trastuzumab
      in HER2-positive breast cancer patients. The anti-proliferative effects of
      trastuzumab combined with IGF1R TKIs BMS-536924 or NVP-AEW541 were measured in
      nine HER2-positive cell lines. IGF1R and phosphorylated IGF1R/insulin receptor
      (pIGF1R/IR) were measured by immunohistochemistry in 160 tumour samples from
      trastuzumab-treated patients (ICORG 06-22). The HER2-positive cell lines
      displayed varying sensitivity to IGF1R TKIs alone (IC(50)s: 0.7 to >10 MUM).
      However, when combined with trastuzumab, a significantly enhanced effect was
      observed in five cell lines treated with BMS-536924, and three with NVP-AEW541.
      While IGF1R levels correlated with reduced response to NVP-AEW541 alone, neither
      IGF1R nor pIGF1R were predictive of response to BMS-536924 or NVP-AEW541 in
      combination with trastuzumab. Low HER2 levels correlated with response to BMS
      536924 in combination with trastuzumab. Akt levels correlated with improved
      response to trastuzumab and NVP-AEW541 (P = 0.039). Cytoplasmic IGF1R staining
      was observed in all tumours, membrane IGF1R was detected in 13.8 %, and pIGF1R/IR
      was detected in 48.8 %. Although membrane IGF1R staining was associated with
      larger tumour size (P = 0.041), and lower tumour grade (P = 0.024), no
      association between IGF1R or pIGF1R/IR and patient survival was observed. In
      conclusion, while neither IGF1R expression nor activation was predictive of
      response to trastuzumab, these pre-clinical data provide evidence that co
      targeting HER2 and IGF1R may be beneficial in some HER2-amplified breast cancers.

PMID- 23117853
TI  - Alcohol consumption suppresses mammary tumor metastasis in a syngeneic tumor
      transplantation model.
AB  - Epidemiological studies indicate a positive correlation between alcohol
      consumption and the risk of developing breast cancer. However, little is known
      about whether alcohol consumption affects breast cancer metastasis. Considering
      that the primary cause of death in breast cancer patients is due to metastasis,
      further insight into whether alcohol consumption influences disease progression
      and survival is needed. We tested the effect of alcohol consumption on breast
      cancer metastasis using the 4T1.2 syngeneic mammary tumor model in Balb/c mice.
      The treatment groups included a High-consuming group (18 % w/v alcohol in
      drinking water), a Moderate-consuming group (5 % w/v), a Low-consuming group (1 %
      w/v), and a Water-drinking control group. 4T1.2 mammary tumor cells were injected
      orthotopically into the mammary fat pad. Metastases were enumerated in lungs and
      in distant mammary glands 4 weeks after injection. Consumption of High alcohol
      protected against metastasis, as High-consuming mice typically had 65-75 % fewer
      metastases compared to Water-drinking controls. A suggestive reduction in tumor
      spread was observed in the Moderate-drinking group, although the effects did not
      reach statistical significance. Consumption of the Low alcohol dose did not
      affect metastasis. CXCR4 expression in the primary tumors was significantly
      reduced by High alcohol consumption; however, expression of this chemokine
      receptor in the primary tumor did not correlate with metastatic potential.
      Additional studies were conducted to test for possible direct effects of 0.3 %
      w/v ethanol on tumor cell proliferation, migration, invasion, and colony
      formation of 4T1.2 cells in vitro. Our results indicate that, for this murine
      model, alcohol consumption does not exacerbate tumor metastasis, and that High
      alcohol consumption reduces tumor spread.

PMID- 23117854
TI  - Pattern of follow-up care and early relapse detection in breast cancer patients.
AB  - Routine breast cancer follow-up aims at detecting second primary breast cancers
      and loco regional recurrences preclinically. We studied breast cancer follow-up
      practice and mode of relapse detection during the first 5 years of follow-up to
      determine the efficiency of the follow-up schedule. The Netherlands Cancer
      Registry provided data of 6,509 women, operated for invasive non-metastatic
      breast cancer in 2003-2004. In a random sample including 144 patients, adherence
      to follow-up guideline recommendations was studied. Mode of relapse detection was
      studied in 124 patients with a second primary breast cancer and 160 patients with
      a loco regional recurrence. On average 13 visits were performed during the first
      5 years of the follow-up, whereas nine were recommended. With one, two and three
      medical disciplines involved, the number of visits was 9, 14 and 18,
      respectively. Seventy-five percent (93/124) of patients with a second primary
      breast cancer, 42 % (31/74) of patients with a loco regional recurrence after
      breast conserving surgery and 28 % (24/86) of patients with a loco regional
      recurrence after mastectomy had no symptoms at detection. To detect one loco
      regional recurrence or second primary breast cancer preclinically, 1,349 physical
      examinations versus 262 mammography and/or MRI tests were performed. Follow-up
      provided by only one discipline may decrease the number of unnecessary follow-up
      visits. Breast imaging plays a major and physical examination a minor role in the
      early detection of second primary breast cancers and loco regional recurrences.
      The yield of physical examination to detect relapses early is low and should
      therefore be minimised.

PMID- 23117855
TI  - The SLC4A7 variant rs4973768 is associated with breast cancer risk: evidence from
      a case-control study and a meta-analysis.
AB  - Recent genome-wide association study has identified a genetic variant rs4973768,
      located in 3'-UTR of solute carrier family 4, sodium bicarbonate cotransporter,
      member 7 (SLC4A7), was associated with increased risk of breast cancer (BC).
      However, several following replication studies cannot yield consistent results.
      We thus conducted a hospital-based case-control study including 485 patients and
      514 controls, combined a meta-analysis including 108,632 cases and 135,818
      controls to explore the relationship between this variant and BC risk. Our case
      control study showed that rs4973768 was significantly associated with increased
      BC risk with the odds ratio (OR) of 1.29 (95 % confidence interval [CI]: 1.04
      1.60) under the allelic model. In addition, the meta-analysis also indicated that
      the variant slightly increased the risk of BC with the pooled OR of the per
      allele effect being 1.08 (95 % CI: 1.04-1.11) although with significant
      heterogeneity between studies. Stratified analyses showed that ethnicity, sample
      size, and study design may explain part of the heterogeneity. Moreover, the
      bioinformatics analysis suggested that this variant may influence the
      transcriptional capacity of SLC4A7. In summary, our results showed that the
      SLC4A7 variant, rs4973768, is associated with risk of BC although the underlying
      biologic mechanism warrants further studies.

PMID- 23117856
TI  - Erythropoietin receptor expression and its relationship with trastuzumab response
      and resistance in HER2-positive breast cancer cells.
AB  - Resistance to trastuzumab is a major issue in the treatment of human epidermal
      growth factor receptor 2 (HER2)-positive breast cancer. Several potential
      resistance mechanisms have been investigated, but the results are controversial
      and no conclusion has been reached. Erythropoietin receptor (EPOR) may function
      in cell growth, and expressed in various cancer cells. Because the downstream
      signaling pathways for EPOR and HER2 partially overlapped, we hypothesized that
      EPOR may play a role in the inhibition effect of trastuzumab and resistance to
      trastuzumab. Here, we detected the expression of EPOR mRNA and protein in HER2
      positive breast cancer cell lines and tissues. EPOR expressed in SKBR3, MDA-MB
      453, and UACC-812 cell lines, but not in BT474. Of the 55 HER2-positive cancer
      tissues, EPOR was positive in 42 samples and highly expressed (H-score >= 25) in
      24 by immunohistochemistry. The difference between EPOR expression and Ki67 index
      was significant (P = 0.033), and EPOR expression also positively correlated with
      higher pathological stage (Spearman correlation coefficient = 0.359; P = 0.007).
      Exogenous EPO antagonized trastuzumab-induced inhibition of cell proliferation in
      HER2/EPOR dual-positive breast cancer cells. We then exposed SKBR3 cells to
      trastuzumab for 4 months to obtain trastuzumab-resistant SKBR3 cell line, which
      demonstrated higher phosphorylated EPOR level, higher EPO expression and more
      extracellular secretion than non-resistant parental SKBR3 cells. Downregulation
      EPOR expression using short hairpin RNA resensitized trastuzumab-resistant cells
      to this drug, and SKBR3 cells with EPOR downregulation demonstrated attenuated
      trastuzumab resistance after the same resistance induction. EPOR downregulation
      plus trastuzumab produced a synergetic action in the inhibition of cell
      proliferation and invasion in SKBR3 and MDA-MB-453 cell lines. Therefore, EPOR
      expression may be involved in tumor progression and proliferation in HER2
      positive breast cancer. EPO/EPOR contributes to the mechanism of trastuzumab
      resistance in SKBR3 cell lines, and EPOR downregulation can reverse the
      resistance to trastuzumab and increase the inhibition effect of this drug.

PMID- 23117857
TI  - Germline mutations in RAD51C in Jewish high cancer risk families.
AB  - Germline mutations in BRCA1 and BRCA2 account for ~30 % of inherited breast
      cancer. RAD51C was reported as an additional breast/ovarian cancer susceptibility
      gene in some populations. There is a paucity of data on the putative contribution
      of this gene to inherited breast/ovarian cancer in Jewish high risk families.
      High risk Jewish women, none of whom was a carrier of the predominant Jewish
      mutations in BRCA1 or BRCA2, were screened for RAD51C germline mutations by
      direct sequencing of exons and flanking intronic sequences. Overall, 206 high
      risk women, 79 (38.3 %) of Ashkenazi origin, were genotyped for RAD51C mutations:
      190 (92.3 %) with uni- or bilateral breast cancer (mean age at diagnosis 51.3 +/-
      11.1 years), 14 with ovarian cancer (mean age at diagnosis 55.6 +/- 8.7 years),
      and two with both breast and ovarian cancer. No truncating mutations were noted,
      and two previously described missense mutations were detected: p.Ile144Thr and
      p.Thr287Ala in Iraqi and mixed ethnicity Balkan-North African participants,
      respectively. These missense mutations were evolutionarily conserved, possibly
      pathogenic, based on some prediction algorithms, and were not detected in any of
      healthy Iraqi (n = 60) and mixed ethnicity (n = 140), cancer free controls,
      respectively. Germline mutations in RAD51C contribute marginally to breast and
      ovarian cancer susceptibility in ethnically diverse, Jewish high risk families.
      The p.Thr287Ala missense mutation may be a recurring, pathogenic RAD51C mutation
      in ethnically diverse populations.

PMID- 23117858
TI  - The role of chemoprevention in modifying the risk of breast cancer in women with
      atypical breast lesions.
AB  - Women with atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH),
      lobular carcinoma in situ (LCIS), and severe ADH are at increased risk of breast
      cancer, but a systematic quantification of this risk and the efficacy of
      chemoprevention in the clinical setting is still lacking. The objective of this
      study is to evaluate a woman's risk of breast cancer based on atypia type and to
      determine the effect of chemoprevention in decreasing this risk. Review of 76,333
      breast pathology reports from three institutions within Partners Healthcare
      System, Boston, from 1987 to 2010 using natural language processing was carried
      out. This approach identified 2,938 women diagnosed with atypical breast lesions.
      The main outcome of this study is breast cancer occurrence. Of the 2,938 patients
      with atypical breast lesions, 1,658 were documented to have received no
      chemoprevention, and 184/1,658 (11.1 %) developed breast cancer at a mean follow
      up of 68 months. Estimated 10-year cancer risks were 17.3 % with ADH, 20.7 % with
      ALH, 23.7 % with LCIS, and 26.0 % with severe ADH. In a subset of patients
      treated from 1999 on (the chemoprevention era), those who received no
      chemoprevention had an estimated 10-year breast cancer risk of 21.3 %, whereas
      those treated with chemoprevention had a 10-year risk of 7.5 % (p < 0.001).
      Chemoprevention use significantly reduced breast cancer risk for all atypia types
      (p < 0.05). The risk of breast cancer with atypical breast lesions is
      substantial. Physicians should counsel patients with ADH, ALH, LCIS, and severe
      ADH about the benefit of chemoprevention in decreasing their breast cancer risk.

PMID- 23117859
TI  - Pd-catalyzed coupling reaction of fluorinated propargyl amidines with aryl
      iodides.
AB  - Catalyzed by ligand free Pd(OAc)(2), 2,5-disubstituted imidazole was prepared in
      good yield by the reaction of fluorinated propargyl amidines with iodoarene.
      Mechanistic studies indicated that this transformation occurs through a
      nitropalladation-reductive elimination pathway.

PMID- 23117860
TI  - Disinhibition mediates the relationship between ADHD and problematic alcohol use
      in college students.
AB  - OBJECTIVE: High-risk alcohol use among college students has received substantial
      attention in recent years, and intervention and prevention efforts have increased
      dramatically. The current study examined ADHD as a risk factor for problematic
      drinking among college students. Trait disinhibition and difficulty stopping a
      drinking session were examined as potential mechanisms through which ADHD is
      associated with alcohol-related problems. METHOD: Participants included 100 full
      time undergraduate students with (n = 48) and without (n = 52) Diagnostic and
      Statistical Manual of Mental Disorders (4th ed.) ADHD. RESULTS: Students with
      ADHD had higher rates of alcohol-related problems and alcohol-use disorders
      across multiple measures. Both disinhibition and difficulty stopping a drinking
      session independently mediated the relationship between ADHD and negative
      consequences of alcohol use. CONCLUSION: These findings indicate that college
      students with ADHD are at increased risk for alcohol-related problems. Trait
      disinhibition and difficulty stopping a drinking session represent mechanisms of
      high-risk alcohol use among college students with ADHD.

PMID- 23117861
TI  - Tidal cycles of total particulate mercury in the Jade Bay, lower Saxonian Wadden
      Sea, southern North Sea.
AB  - In this study, we evaluate the nature of the relationship between particulate
      matter and total mercury concentrations. For this purpose, we estimate both of
      the two values in water column over 12-h tidal cycles of the Jade Bay, southern
      North Sea. Total particulate mercury in 250 mL water samples was determined by
      oxygen combustion-gold amalgamation. Mercury contents varied from 63 to 259 ng/g
      suspended particulate matter (SPM) or 3.5-52.8 ng/L in surface waters. Total
      particulate mercury content (THg(p)) was positively correlated with (SPM),
      indicating that mercury in tidal waters is mostly associated with (SPM), and that
      tidal variations of total particulate mercury are mainly due to changes in (SPM)
      content throughout the tidal cycle. Maximum values for THg(p) were observed
      during mid-flood and mid-ebb, while the lowest values were determined at low tide
      and high tide. These data suggest that there are no mercury point sources in the
      Jade Bay. Moreover, the THg(p) content at low tide and high tide were
      significantly lower than the values recorded in the bottom sediment of the
      sampling site (>200 ng/g DW), while THg(p) content during the mid-flood and mid
      ebb were comparable to the THg content in the surface bottom sediments.
      Therefore, changes in THg(p) content in the water column due to tidal forcing may
      have resulted from re-suspension of underlying surface sediments with relatively
      high mercury content.

PMID- 23117863
TI  - Spectral algorithms for heterogeneous biological networks.
AB  - Spectral methods, which use information relating to eigenvectors, singular
      vectors and generalized singular vectors, help us to visualize and summarize sets
      of pairwise interactions. In this work, we motivate and discuss the use of
      spectral methods by taking a matrix computation view and applying concepts from
      applied linear algebra. We show that this unified approach is sufficiently
      flexible to allow multiple sources of network information to be combined. We
      illustrate the methods on microarray data arising from a large population-based
      study in human adipose tissue, combined with related information concerning
      metabolic pathways.

PMID- 23117862
TI  - Restoring totipotency through epigenetic reprogramming.
AB  - Epigenetic modifications are implicated in the maintenance and regulation of
      transcriptional memory by marking genes that were previously transcribed to
      facilitate transmission of these expression patterns through cell division.
      During germline specification and maintenance, extensive epigenetic modifications
      are acquired. Yet somehow at fertilization, the fusion of the highly
      differentiated sperm and egg results in formation of the totipotent zygote. This
      massive change in cell fate implies that the selective erasure and maintenance of
      epigenetic modifications at fertilization may be critical for the re
      establishment of totipotency. In this review, we discuss recent studies that
      provide insight into the extensive epigenetic reprogramming that occurs around
      fertilization and the mechanisms that may be involved in the re-establishment of
      totipotency in the embryo.

PMID- 23117864
TI  - Capturing the regulatory interactions of eukaryote genomes.
AB  - A key finding from early genomics research is the remarkable consistency in the
      number of protein-coding regions across diverse species. This has led many
      researchers to look to the cis-regulatory elements of genes as the fundamental
      influence behind evolving gene function and subsequent species diversification.
      Historically, since these elements are often located in vast intergenic and
      intronic regions of the genome, their identification has been recalcitrant. Now,
      with the deluge of whole-genome data from representatives of numerous eukaryotic
      lineages, various approaches have enabled us to begin to recognize features that
      characterize regulatory regions of the genome. Here we endeavour to collate these
      approaches in order to give an overview of the complexities involved in
      extrapolating regulatory signatures. The resource provided by the escalating
      richness of whole-genome datasets enables more sophisticated modelling of these
      regulatory signatures yet at the same time introduces increasing potential for
      noise. While we are only at the advent of making these discoveries, the next
      decade promises to be a very exciting and rewarding time for genome researchers.

PMID- 23117865
TI  - Localized photo-induced voltage with controlled polarity in single K enriched
      MoO3 nanobundle.
AB  - The photo-induced voltage in an individual K enriched MoO(3) nanobundle was
      studied with localized focused laser beam irradiation. Without an external bias
      voltage, a significant photo-induced voltage (36.5 mV) was produced in a single
      nanobundle under low laser power (2.2 mW). Remarkably, the amplitude and polarity
      of the voltage could be controlled by the location of the focused laser spot.
      Unlike the common photo-response that comes from metal-semiconductor junction or
      PN junction in hybrid nanomaterial, the observed photo-induced effect is from the
      nanobundle itself, attributed to the small band gap of the material.

PMID- 23117866
TI  - The T-type Ca2+ channel inhibitor mibefradil inhibits voltage-dependent K+
      channels in rabbit coronary arterial smooth muscle cells.
AB  - We examined the effects of mibefradil, a T-type Ca2+ channel inhibitor, on
      voltage-dependent K+ (Kv) channels in rabbit coronary arterial smooth muscle
      cells using the whole-cell patch clamp technique. Mibefradil reduced the Kv
      current amplitude in a dose-dependent manner, with an apparent K(d) value of 1.08
      MUM. Kv current inhibition by mibefradil was highly voltage-dependent over the
      full activation voltage range (-30 to +10 mV). The decay rate of Kv channel
      inactivation was accelerated by mibefradil without altering the kinetics of
      current activation. The rate constants of association and dissociation were 2.23
      +/- 0.07 MUM-1.s-1 and 2.40 +/- 0.42 s-1, respectively. Mibefradil had no
      significant effect on the steady-state activation or inactivation curves. In the
      presence of mibefradil, the recovery time constant from inactivation was
      decreased, and the application of train pulses (1 or 2 Hz) increased mibefradil
      induced Kv channel inhibition, suggesting that the inhibitory effects of
      mibefradil were use-dependent. The inhibitory effect of mibefradil on Kv channels
      was unaffected by extracellular Ca2+-free conditions. Moreover, the absence of
      ATP inside the pipette did not alter the blocking effect of mibefradil.
      Therefore, we suggest that mibefradil directly inhibited the Kv current,
      independently of Ca2+ channel inhibition.

PMID- 23117867
TI  - A novel Ad5/11 chimeric oncolytic adenovirus for improved glioma therapy.
AB  - Effective therapies are needed for malignant glioma patients because of the poor
      prognosis. Gene therapy combined with virotherapy could be the strategy of
      choice. In this study, we constructed a modified conditionally replicating
      adenoviral vector CRAd5/11-Sp-eGFP. The novel vector has the following features:
      i) the transduction efficiency of CRAd5 was increased using a chimeric fiber 5/11
      consisting of an Ad5 tail and an Ad11 shaft and knob; ii) the tumor-specific
      replication of the vector was improved by utilizing the human survivin promoter
      to control E1 expression and a poly-A signal inserted right after the inverted
      terminal repeat (ITR) to stop the non-specific transcriptional activity of the
      ITR; iii) an expression cassette was inserted into the region between the fiber
      and E4 region for expressing eGFP. In vitro assays demonstrated that the novel
      vector could efficiently replicate and kill human glioma cells. Furthermore,
      CRAd5/11-Sp-eGFP exhibited significantly increased antitumor effects compared
      with the control adenoviruses in a xenograft model of glioma. Our results
      indicate that CRAd5/11-Sp-eGFP represents a promising candidate drug in the
      treatment of malignant gliomas.

PMID- 23117869
TI  - A histomorphometric study of cellular layers after hemiepiphyseal stapling on the
      physeal plate in rabbits.
AB  - BACKGROUND: Epiphyseal stapling has been widely used to correct angular
      deformity. The mechanism, however, has not been well determined. To determine the
      effect of temporary hemiepiphyseal stapling on the cellular layers of the physis,
      a histomorphometric study was performed using immature rabbits. METHODS: Distal
      lateral epiphyseal stapling of the right femur was performed on 6-week-old New
      Zealand white rabbits. Thirty rabbits were randomly assigned to five groups, and
      six rabbits in each group were analyzed weekly for up to 5 weeks. RESULTS: The
      distal femur was deformed into the valgus, and the anatomical lateral distal
      femoral angle decreased with the passage of time. In the sequential
      histomorphometry of the operated physeal plate, the area ratio of each layer,
      compared to the control side, decreased every week. The total area of the physeal
      plate had decreased up to 60 % at the 5th week compared to the area of the 1st
      week, and the area of the proliferative layer decreased by the greatest amount
      among the three layers. CONCLUSIONS: Our findings suggest that the proliferation
      of chondrocytes seemed to be more suppressed by the compression of the stapling,
      thereby slowing the growth rate, although hypertrophy of the chondrocytes was
      also suppressed.

PMID- 23117870
TI  - Fabricating metamaterials using the fiber drawing method.
AB  - Metamaterials are man-made composite materials, fabricated by assembling
      components much smaller than the wavelength at which they operate (1). They owe
      their electromagnetic properties to the structure of their constituents, instead
      of the atoms that compose them. For example, sub-wavelength metal wires can be
      arranged to possess an effective electric permittivity that is either positive or
      negative at a given frequency, in contrast to the metals themselves (2). This
      unprecedented control over the behaviour of light can potentially lead to a
      number of novel devices, such as invisibility cloaks (3), negative refractive
      index materials (4), and lenses that resolve objects below the diffraction limit
      (5). However, metamaterials operating at optical, mid-infrared and terahertz
      frequencies are conventionally made using nano- and micro-fabrication techniques
      that are expensive and produce samples that are at most a few centimetres in size
      (6-7). Here we present a fabrication method to produce hundreds of meters of
      metal wire metamaterials in fiber form, which exhibit a terahertz plasmonic
      response (8). We combine the stack-and-draw technique used to produce
      microstructured polymer optical fiber (9) with the Taylor-wire process (10),
      using indium wires inside polymethylmethacrylate (PMMA) tubes. PMMA is chosen
      because it is an easy to handle, drawable dielectric with suitable optical
      properties in the terahertz region; indium because it has a melting temperature
      of 156.6  degrees C which is appropriate for codrawing with PMMA. We include an
      indium wire of 1 mm diameter and 99.99% purity in a PMMA tube with 1 mm inner
      diameter (ID) and 12 mm outside diameter (OD) which is sealed at one end. The
      tube is evacuated and drawn down to an outer diameter of 1.2 mm. The resulting
      fiber is then cut into smaller pieces, and stacked into a larger PMMA tube. This
      stack is sealed at one end and fed into a furnace while being rapidly drawn,
      reducing the diameter of the structure by a factor of 10, and increasing the
      length by a factor of 100. Such fibers possess features on the micro- and nano-
      scale, are inherently flexible, mass-producible, and can be woven to exhibit
      electromagnetic properties that are not found in nature. They represent a
      promising platform for a number of novel devices from terahertz to optical
      frequencies, such as invisible fibers, woven negative refractive index cloths,
      and super-resolving lenses.

PMID- 23117871
TI  - Candidates with a cure.
AB  - Texas Medical Association physicians and alliance members are poised to fill as
      many as eight seats in the Texas House and Senate and one in the U.S. Congress in
      the Nov. 6 election. It's an example of how TEXPAC and the TMA Alliance are
      working to make sure lawmakers hear the voices of physicians and their patients.

PMID- 23117868
TI  - Imaging multiple sclerosis and other neurodegenerative diseases.
AB  - Although the prevalence of neurodegenerative diseases is increasing as a
      consequence of the growing aging population, the exact pathophysiological
      mechanisms leading to these diseases remains obscure. Multiple sclerosis (MS), an
      autoimmune disease of the central nervous system and the most frequent cause of
      disability among young people after traumatic brain injury, is characterized by
      inflammatory/demyelinating and neurodegenerative processes that occurr earlier in
      life. The ability to make an early diagnosis of MS with the support of
      conventional MRI techniques, provides the opportunity to study neurodegeneration
      and the underlying pathophysiological processes in earlier stages than in
      classical neurodegenerative diseases. This review summarizes mechanisms of
      neurodegeneration common to MS and to Alzheimer disease, Parkinson disease, and
      amiotrophic lateral sclerosis, and provides a brief overview of the neuroimaging
      studies employing MRI and PET techniques to investigate and monitor
      neurodegeneration in both MS and classical neurodegenerative diseases.

PMID- 23117872
TI  - Cost control.

PMID- 23117873
TI  - Medical crisis response.

PMID- 23117874
TI  - Specifics, please.

PMID- 23117875
TI  - An apt app.

PMID- 23117876
TI  - Health insurance coverage in the Houston-Galveston area under the patient
      protection and affordable care act.
AB  - This study projects the number of nonelderly people who could gain coverage under
      the Patient Protection and Affordable Care Act (PPACA) for the period from 2014
      through 2020 in the 13-county Houston-Galveston area region. The major PPACA
      provisions aimed at expanding coverage as well as the populations targeted by
      those provisions are described. Projections of the impact of PPACA on coverage in
      the area are based on estimates of growth in the size of targeted populations in
      each county and the anticipated responses of those populations to the major
      provisions of PPACA. The projections indicate that, if fully implemented, PPACA
      could cut the uninsurance rate in the region by half, from 26% in 2010 to 13% in
      2020. This change translates into health insurance coverage for approximately 2
      million additional people, from the current 4.2 million to a projected 5.9
      million. The number of Medicaid enrollees could increase by an estimated 600,000
      (a 79% increase), although private insurance coverage, which could increase by as
      much as 1 million enrollees (a 30% increase), will remain the primary source of
      coverage for most people. Coverage gains from PPACA will vary considerably by
      county, depending on the age-income-citizenship characteristics of the
      population, current uninsurance rates, and the rate of population growth.

PMID- 23117877
TI  - Enzymatic assay for quantitative analysis of (D)-2-hydroxyglutarate.
AB  - Levels of (D)-2-hydroxyglutarate [D2HG, (R)-2-hydroxyglutarate] are increased in
      some metabolic diseases and in neoplasms with mutations in the isocitrate
      dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) genes. Determination
      of D2HG is of relevance to diagnosis and monitoring of disease. Standard
      detection methods of D2HG levels are liquid-chromatography-mass spectrometry or
      gas-chromatography-mass spectrometry. Here we present a rapid, inexpensive and
      sensitive enzymatic assay for the detection of D2HG levels. The assay is based on
      the conversion of D2HG to alpha-ketoglutarate (alphaKG) in the presence of the
      enzyme (D)-2-hydroxyglutarate dehydrogenase (HGDH) and nicotinamide adenine
      dinucleotide (NAD(+)). Determination of D2HG concentration is based on the
      detection of stoichiometrically generated NADH. The quantification limit of the
      enzymatic assay for D2HG in tumor tissue is 0.44 MUM and in serum 2.77 MUM. These
      limits enable detection of basal D2HG levels in human tumor tissues and serum
      without IDH mutations. Levels of D2HG in frozen and paraffin-embedded tumor
      tissues containing IDH mutations or in serum from acute myeloid leukemia patients
      with IDH mutations are significantly higher and can be easily identified with
      this assay. In conclusion, the assay presented is useful for differentiating
      basal from elevated D2HG levels in tumor tissue, serum, urine, cultured cells and
      culture supernatants.

PMID- 23117879
TI  - Biting deterrence and insecticidal activity of hydrazide-hydrazones and their
      corresponding 3-acetyl-2,5-disubstituted-2,3-dihydro-1,3,4-oxadiazoles against
      Aedes aegypti.
AB  - BACKGROUND: Taking into account the improvement in insecticidal activity by the
      inclusion of fluorine in the hydrazone moiety, the authors synthesized new 4
      fluorobenzoic acid hydrazides and 3-acetyl-2,5-disubstituted-2,3-dihydro-1,3,4
      oxadiazoles, substituting a phenyl group or a heteroaryl ring carrying one or two
      atoms of F, Cl and Br, and investigated their biting deterrent and larvicidal
      activities against Aedes aegypti for the first time. RESULTS: The compound 3
      acetyl-5-(4-fluorophenyl)-2-[4-(dimethylamino)phenyl]-2,3-dihydro-1,3,4
      oxadiazole (17) produced the highest biting deterrent activity (BDI = 1.025)
      against Ae. Aegypti, followed by 4-fluorobenzoic acid [(phenyl)methylene]
      hydrazide (1). These activity results were similar to those of N,N-diethyl-meta
      toluamide (DEET), which showed a proportion not biting of 0.8-0.92. When
      compounds 1 and 17 were tested on cloth worn on human volunteers, compound 1 was
      not repellent for some volunteers until present in excess of 500 nmol cm(-2) ,
      while compound 17 was not repellent at the highest concentration tested (1685
      nmol cm(-2) ). In the larvicidal screening bioassays, only compounds 10, 11, 12
      and 17 showed 100% mortality at the highest screening dose of 100 ppm against Ae.
      aegypti larvae. Compounds 11 and 12 with LD50 values of 24.1 and 30.9 ppm showed
      significantly higher mortality than 10 (80.3 ppm) and 17 (58.7 ppm) at 24-h post
      treatment. CONCLUSION: The insecticidal and biting deterrent activities were
      correlated with the presence of a halogen atom on the phenyl or heteroaryl
      substituent of the hydrazone moiety.

PMID- 23117878
TI  - Complications, consequences, and practice patterns of endobronchial ultrasound
      guided transbronchial needle aspiration: Results of the AQuIRE registry.
AB  - BACKGROUND: Few studies of endobronchial ultrasound-guided transbronchial needle
      aspiration(EBUS-TBNA) have been large enough to identify risk factors for
      complications. The primary objective of this study was to quantify the incidence
      of and risk factors for complications in patients undergoing EBUS-TBNA. METHODS:
      Data on prospectively enrolled patients undergoing EBUS-TBNA in the American
      College of Chest Physicians Quality Improvement Registry, Evaluation, and
      Education (AQuIRE)database were extracted and analyzed for the incidence,
      consequences, and predictors of complications. RESULTS: We enrolled 1,317
      patients at six hospitals. Complications occurred in 19 patients (1.44%;95% CI,
      0.87%-2.24%). Transbronchial lung biopsy (TBBx) was the only risk factor for
      complications,which occurred in 3.21% of patients who underwent the procedure and
      in 1.15% of those who did not (OR, 2.85; 95% CI, 1.07-7.59; P 5 .04).
      Pneumothorax occurred in seven patients(0.53%; 95% CI, 0.21%-1.09%). Escalations
      in level of care occurred in 14 patients (1.06%;95% CI, 0.58%-1.78%); its risk
      factors were age . 70 years (OR, 4.06; 95% CI, 1.36-12.12; P 5 .012),inpatient
      status (OR, 4.93; 95% CI, 1.30-18.74; P 5 .019), and undergoing deep sedation or
      general anesthesia (OR, 4.68; 95% CI, 1.02-21.61; P 5 .048). TBBx was performed
      in only 12.6% of patients when rapid on site cytologic evaluation (ROSE ) was
      used and in 19.1% when it was not used ( P 5 .006).Interhospital variation in
      TBBx use when ROSE was used was significant ( P , .001). CONCLUSIONS: TBBx was
      the only risk factor for complications during EBUS-TBNA procedures.ROSE
      significantly reduced the use of TBBx.

PMID- 23117880
TI  - Asymptomatic brain metastases in patients with cutaneous metastatic malignant
      melanoma.
AB  - The aim of the study was to identify the frequency of asymptomatic brain
      metastases detected by computed tomography (CT) scans in patients with metastatic
      cutaneous melanoma referred to first-line systemic treatment. Between 1995 and
      2009, 697 Danish patients were screened with a contrast-enhanced CT scan of the
      brain before the start of interleukin-2 (IL-2)-based immunotherapy. Among the 697
      patients, 80 had asymptomatic brain metastases (12%). Patients' characteristics
      did not differ significantly between groups with and without brain metastases.
      Patients received systemic treatment (IL-2-based or cytotoxic chemotherapy),
      local treatment (stereotactic radiotherapy, whole-brain radiotherapy or surgery),
      or best supportive care only. The survival was significantly shorter for patients
      with asymptomatic brain metastases compared with patients without brain
      metastases (P<0.0001). The median survival was 4.5 versus 9.2 months; 1-year
      survival was 12.5 versus 38.4% for patients with or without asymptomatic brain
      metastases, respectively. We conclude that 12% of patients with metastatic
      cutaneous melanoma who qualified clinically for IL-2 treatment had asymptomatic
      brain metastases, detected by CT scans with contrast. Proper staging of
      metastatic cutaneous melanoma including contrast-enhanced CT of neck, thorax, and
      abdomen and contrast-enhanced MRI of the brain is mandatory, as systemic
      treatment options with comparable safety and efficacy in patients with and
      without brain metastases have emerged.

PMID- 23117881
TI  - Identification of an Aurora kinase inhibitor specific for the Aurora B isoform.
AB  - Aurora kinases play an important role in chromosome alignment, segregation, and
      cytokinesis during mitosis. In the present study, we used a ligand docking method
      to explore the novel scaffold of potential Aurora B inhibitors. One thousand
      compounds from our in-house compound library were screened against the Aurora B
      structure and one compound, (E)-3-((E)-4-(benzo[d][1,3]dioxol-5-yl)-2-oxobut-3-en
      1-ylidene)indolin-2-one (designated herein as HOI-07) was selected for further
      study. HOI-07 potently inhibited in vitro Aurora B kinase activity in a dose
      dependent manner, without obvious inhibition of another 49 kinases, including
      Aurora A. This compound suppressed Aurora B kinase activity in lung cancer cells,
      evidenced by the inhibition of the phosphorylation of histone H3 on Ser10 in a
      dose- and time-dependent manner. This inhibition resulted in apoptosis induction,
      G(2)-M arrest, polyploidy cells, and attenuation of cancer cell anchorage
      independent growth. Moreover, knocking down the expression of Aurora B
      effectively reduced the sensitivity of cancer cells to HOI-07. Results of an in
      vivo xenograft mouse study showed that HOI-07 treatment effectively suppressed
      the growth of A549 xenografts, without affecting the body weight of mice. The
      expression of phospho-histone H3, phospho-Aurora B, and Ki-67 was also suppressed
      in the HOI-07 treatment group. Taken together, we identified HOI-07 as a specific
      Aurora B inhibitor, which deserves further investigation.

PMID- 23117883
TI  - CD40-mediated activation of chronic lymphocytic leukemia cells promotes their
      CD44-dependent adhesion to hyaluronan and restricts CCL21-induced motility.
AB  - Microenvironmental interactions are crucial for the survival and proliferation of
      chronic lymphocytic leukemia (CLL) cells. CD4+ T cells that express CD40 ligand
      (CD40L), along with other accessory immune and stromal cells within CLL lymph
      nodes, provide signals needed for activation and outgrowth of the tumor clone.
      Furthermore, correct positioning of CLL cells within lymphoid subcompartments is
      essential for the transmission of these supportive signals. Thereby, interstitial
      cell migration and adhesion events, influenced by activational stimuli, determine
      CLL cell localization. CD44 has been implicated in cell activation, migration,
      and tissue retention via binding to its extracellular matrix ligand hyaluronan
      (HA). In this study, we investigated the role of CD44-HA interactions for CLL
      positioning and interaction with supportive microenvironments in peripheral lymph
      nodes, focusing on its regulation via CD40L-dependent, T-cell-mediated activation
      of CLL cells. We found that hyaluronan triggered a robust CCL21-induced motility
      of resting CLL cells. However, CD40L stimulation promoted the firm, CD44-mediated
      adhesion of CLL cells to hyaluronan, antagonizing their motile behavior. N-linked
      glycosylations of CD44, particularly associated with the variant isoform CD44v6
      after CD40L activation, seemed to facilitate hyaluronan recognition by CD44. We
      propose that the CD40L-CD40 signaling axis provides a stop signal to motile CLL
      cells within lymph node compartments by inducing high avidity CD44-HA adhesion.
      This might retain CLL cells close to T-cell stimuli and facilitate essential
      interactions with hyaluronan-bearing stromal cells, collectively promoting CLL
      cell proliferation and survival.

PMID- 23117882
TI  - ABL regulation by AXL promotes cisplatin resistance in esophageal cancer.
AB  - Esophageal adenocarcinoma (EAC) is characterized by resistance to chemotherapy
      and poor outcome. Although cisplatin (CDDP) has been used as a first-line therapy
      in patients with EAC, resistance remains a major clinical problem. The AXL
      receptor tyrosine kinase, originally isolated as a transforming gene from
      leukemia, is overexpressed in several solid tumors. Herein, we assessed AXL
      protein expression in human EACs and examined its role in CDDP resistance in
      human EAC cells. AXL overexpression was detected in more than 50% of tumors
      examined. Elevating AXL in nonoverexpressing cells doubled the CDDP IC(50) and
      increased cell survival three-fold, while attenuating AXL in overexpressing cells
      reduced survival two-fold. The effects of AXL modulation on cell survival were
      associated with changes in cellular and molecular markers of apoptosis.
      Mechanistic investigations revealed that AXL blocked CDDP-induced activation of
      endogenous p73beta (TP73), reducing its protein half-life, and inhibited CDDP
      induced levels of p-c-ABL(Y412) and p-p73beta(Y99). These changes were associated
      with a disruption of c-ABL/p73beta protein interactions due to association with c
      ABL in the cytoplasm, thereby blocking nuclear accumulation of c-ABL and
      phosphorylation of p73beta in response to DNA damage. Together, our results
      establish that AXL promotes CDDP resistance in esophageal adenocarcinoma and
      argue that therapeutic targeting of AXL may sensitize these cancers to DNA
      damaging drugs.

PMID- 23117884
TI  - Production of gastrointestinal tumors in mice by modulating latent TGF-beta1
      activation.
AB  - TGF-beta and its signaling pathways are important mediators in the suppression of
      cancers of the gastrointestinal tract. TGF-beta is released from cells in a
      latent complex consisting of TGF-beta, the TGF-beta propeptide [latency
      associated protein (LAP)], and a latent TGF-beta binding protein (LTBP). We
      previously generated mice in which the LTBP-binding cysteine residues in LAP TGF
      beta1 were mutated to serine precluding covalent interactions with LTBP. These
      Tgfb1(C33S/C33S) mice develop multiorgan inflammation and tumors consistent with
      reduced TGF-beta1 activity. To test whether further reduction in active TGF-beta
      levels would yield additional tumors and a phenotype more similar to Tgfb1(-/-)
      mice, we generated mice that express TGF-beta1(C33S) and are deficient in either
      integrin beta8 or TSP-1, known activators of latent TGF-beta1. In addition, we
      generated mice that have one mutant allele and one null allele at the Tgfb1
      locus, reasoning that these mice should synthesize half the total amount of TGF
      beta1 as Tgfb1(C33S/C33S) mice, and the amount of active TGF-beta1 would be
      correspondingly decreased compared with Tgfb1(C33S/C33S) mice. These compound
      mutant mice displayed more severe inflammation and higher tumor numbers than the
      parental Tgfb1(C33S/C33S) animals. The level of active TGF-beta1 in compound
      mutant mice seemed to be decreased compared with Tgfb1(C33S/C33S) mice as
      determined from analyses of surrogate markers of active TGF-beta, such as P
      Smad2, C-Myc, KI-67, and markers of cell-cycle traverse. We conclude that these
      mutant mice provide a useful system for modulating TGF-beta levels in a manner
      that determines tumor number and inflammation within the gastrointestinal tract.

PMID- 23117885
TI  - Androgen receptor splice variants mediate enzalutamide resistance in castration
      resistant prostate cancer cell lines.
AB  - Persistent androgen receptor (AR) transcriptional activity underlies resistance
      to AR-targeted therapy and progression to lethal castration-resistant prostate
      cancer (CRPC). Recent success in retargeting persistent AR activity with next
      generation androgen/AR axis inhibitors such as enzalutamide (MDV3100) has
      validated AR as a master regulator during all stages of disease progression.
      However, resistance to next generation AR inhibitors limits therapeutic efficacy
      for many patients. One emerging mechanism of CRPC progression is AR gene
      rearrangement, promoting synthesis of constitutively active truncated AR splice
      variants (AR-V) that lack the AR ligand-binding domain. In this study, we show
      that cells with AR gene rearrangements expressing both full-length and AR-Vs are
      androgen independent and enzalutamide resistant. However, selective knock-down of
      AR-V expression inhibited androgen-independent growth and restored responsiveness
      to androgens and antiandrogens. In heterogeneous cell populations, AR gene
      rearrangements marked individual AR-V-dependent cells that were resistant to
      enzalutamide. Gene expression profiling following knock-down of full-length AR or
      AR-Vs showed that AR-Vs drive resistance to AR-targeted therapy by functioning as
      constitutive and independent effectors of the androgen/AR transcriptional
      program. Further, mitotic genes deemed previously to be unique AR-V targets were
      found to be biphasic targets associated with a proliferative level of signaling
      output from either AR-Vs or androgen-stimulated AR. Overall, these studies
      highlight AR-Vs as key mediators of persistent AR signaling and resistance to the
      current arsenal of conventional and next generation AR-directed therapies,
      advancing the concept of AR-Vs as therapeutic targets in advanced disease.

PMID- 23117886
TI  - SpliceArray profiling of breast cancer reveals a novel variant of NCOR2/SMRT that
      is associated with tamoxifen resistance and control of ERalpha transcriptional
      activity.
AB  - Gene expression profiling aimed at classifying and prognosing breast cancer has
      yielded signatures with little, if any, concordance. However, expression arrays
      used in these studies do not discriminate alternate RNA splice isoforms that vary
      widely in cancer and may resolve this problem. In this study, we profiled splice
      isoforms in a panel of tamoxifen-sensitive and -resistant cell lines, defining a
      novel variant (BQ323636.1) of the nuclear receptor corepressor 2 (NCOR2) that was
      associated with tamoxifen resistance. Overexpression of this variant in a
      tamoxifen-sensitive cell line induced its resistance to tamoxifen. We confirmed
      our initial findings from cell lines in 77 breast tumors from a Chinese cohort,
      where BQ323636.1 expression was higher in tamoxifen-resistant patients than
      tamoxifen-sensitive patients. For patients who were estrogen receptor (ER)
      positive and had received tamoxifen treatment, higher BQ323636.1 expression level
      correlated with distant metastasis. High expression level of BQ323636.1 was found
      to be associated with poorer overall and disease-free survival for patients who
      had received tamoxifen treatment. Notably, higher BQ323636.1 versus NCOR2 wild
      type ratio was also associated with negative ER and progesterone receptor (PR)
      status, and triple-negative status (ER-/PR-/HER2- receptor status). Mechanistic
      investigations showed that under conditions of tamoxifen exposure, BQ323636.1
      suppressed the transcriptional activity of ERalpha, exhibiting promoter
      regulating functions. Our findings highlight a novel splice variant of the
      ERalpha corepressor NCOR2 as a candidate biomarker in breast cancer that not only
      predicts tamoxifen response but may be targeted to overcome tamoxifen resistance.

PMID- 23117887
TI  - PNUTS functions as a proto-oncogene by sequestering PTEN.
AB  - PTEN is a well-defined tumor suppressor gene that antagonizes the PI3K/Akt
      pathway to regulate a multitude of cellular processes, such as survival, growth,
      motility, invasiveness, and angiogenesis. While the functions of PTEN have been
      studied extensively, the regulation of its activity during normal and disease
      conditions still remains incompletely understood. In this study, we identified
      the protein phosphatase-1 nuclear targeting subunit PNUTS (PPP1R10) as a PTEN
      associated protein. PNUTS directly interacted with the lipid-binding domain (C2
      domain) of PTEN and sequestered it in the nucleus. Depletion of PNUTS leads to
      increased apoptosis and reduced cellular proliferation in a PTEN-dependent
      manner. PNUTS expression was elevated in certain cancers compared with matched
      normal tissues. Collectively, our studies reveal PNUTS as a novel PTEN regulator
      and a likely oncogene.

PMID- 23117888
TI  - Acute vasoreactivity testing with nicardipine in patients with pulmonary arterial
      hypertension.
AB  - Acute vasoreactivity testing for patients with pulmonary arterial hypertension
      (PAH) has been reported to be useful to identify patients with sustained
      beneficial response to oral calcium-channel blockers (CCBs), but there is a risk
      of exacerbation during the testing with oral CCBs. Therefore, we developed a
      testing method utilizing intravenous nicardipine, a short-acting CCB, and
      examined the safety and usefulness of acute vasoreactivity testing with
      nicardipine in PAH patients. Acute vasoreactivity testing with nicardipine was
      performed in 65 PAH patients. Nicardipine was administered by short-time
      continuous infusion (1 MUg.kg-1.min-1 for 5 min and 2 MUg.kg-1.min-1 for 5 min)
      followed by bolus injection (5 MUg/kg). Hemodynamic responses were continuously
      measured using a right heart catheter. Acute responders were defined as patients
      who showed a decrease in mean pulmonary artery pressure of at least 10 mmHg to an
      absolute level below 40 mmHg with preserved or increased cardiac output. Two
      acute responders and sixty-three non-acute responders were identified. There was
      no hemodynamic instability requiring additional inotropic agents or death during
      the testing. Acute responders had good responses to long-term oral CCBs. The
      acute vasoreactivity testing with nicardipine might be safe and useful for
      identifying CCB responders in PAH patients.

PMID- 23117890
TI  - Colloidal domain lithography in multilayers with perpendicular anisotropy: an
      experimental study and micromagnetic simulations.
AB  - Currently, much attention is being paid to patterned multilayer systems in which
      there exists a perpendicular magnetic anisotropy, because of their potential
      applications in spintronics devices and in a new generation of magnetic storage
      media. To further improve their performance, different patterning techniques can
      be used, which render them suitable also for other applications. Here we show
      that He(+) 10 keV and Ar(+) 100 keV ion bombardment of (Ni(80)Fe(20)-2 nm/Au-2
      nm/Co-0.6 nm/Au-2 nm)(10) multilayers through colloidal mask enables magnetic
      patterning of regularly arranged cylindrical magnetic domains, with perpendicular
      anisotropy, embedded in a non-ferromagnetic matrix or in a ferromagnetic matrix
      with magnetization oriented along the normal. These domains form an almost
      perfect two-dimensional hexagonal lattice with a submicron period and a large
      correlation length in a continuous and flat multilayer system. The magnetic
      anisotropy of these artificial domains remains unaffected by the magnetic
      patterning process, however the magnetization configuration of such a system
      depends on the magnetic properties of the matrix. The micromagnetic simulations
      were used to explain some of the features of the investigated patterned
      structures.

PMID- 23117889
TI  - Isolation, characterization and antifungal activity of proteinase inhibitors from
      Capsicum chinense Jacq. Seeds.
AB  - Capsicum species belong to the Solanaceae family and have great social, economic
      and agronomical significance. The present research presents data on the isolation
      and characterization of Capsicum chinense Jacq. peptides which were scrutinized
      in relation to their toxicity towards a diverse set of yeast species. The protein
      extract was separated with C18 reverse-phase chromatography in high performance
      liquid chromatography, resulting in three different peptide enriched fractions
      (PEFs) termed PEF1, PEF2 and PEF3. Tricine-SDS-PAGE of the PEF2 revealed peptides
      with molecular masses of approximately 5.0 and 8.5 kDa. These PEFs also exhibited
      strong antifungal activity against different yeasts. In the presence of the PEF2,
      Candida tropicalis exhibited morphological changes, including cellular
      agglomeration and formation of pseudohyphae. Determined N-terminal sequences of
      PEF2 and PEF3 were proven to be highly homologous to serine proteinase
      inhibitors, when analysed by comparative database sequence tools. For this reason
      were performed protease inhibitory activity assay. The PEFs displayed high
      inhibitory activity against trypsin and low inhibitory activity against
      chymotrypsin. PEF2 and PEF3 were considerably unsusceptible to a broad interval
      of pH and temperatures. Due to the myriad of application of Proteinase inhibitors
      (PIs) in fields ranging from plant protection against pathogens and pests to
      medicine such as in cancer and virus replication inhibition, the discovery of new
      PIs with new properties are of great interest.

PMID- 23117892
TI  - Application of pediatric balance scales in children with cerebral palsy.

PMID- 23117891
TI  - Purification and biochemical characterisation of a glucose-6-phosphate
      dehydrogenase from the psychrophilic green alga Koliella antarctica.
AB  - Psychrophilic organisms have evolved a number of modifications of cellular
      structures to survive in the cold environment; among them it is worth noting an
      increased efficiency of enzymes at lower temperatures. Glucose-6-phosphate
      dehydrogenase (G6PDH; EC 1.1.1.49) was purified and characterised from the
      psychrophilic green alga Koliella antarctica (Trebouxiophyceae, Chlorophyta) from
      the Ross Sea (Antarctica). It was possible to isolate a single G6PDH using
      biochemical strategies; its maximum activity was measured at 35  degrees C, and
      the enzyme showed an E (a) of 39.6 kJ mol(-1). This protein reacted with
      antibodies raised against higher plants plastidic isoforms. KaG6PDH showed
      peculiar kinetic properties, with a K (iNADPH) value lower than [Formula: see
      text]. Notably, catalytic activity was inactivated in vitro by DTT and
      chloroplastic thioredoxin f. These biochemical properties of G6PDH are discussed
      with respect to higher plant G6PDHs and the adaptation of K. antarctica to polar
      low-temperature environment.

PMID- 23117893
TI  - Paroxysmal periodic dystonic postures in an infant with 18q23 deletion syndrome.
AB  - The 18q23 deletion syndrome is characterized by diverse neurological and
      psychiatric features, including developmental delays, epilepsy, and autism. We
      report on a female infant with an 18q23 deletion who displayed atypical periodic
      dystonic postures. Video-electroencephalography recordings were used to evaluate
      the involuntary nonepileptic movements in the infant. Although nonepileptic
      involuntary movements have been rarely reported in adult patients, there are no
      reports of paroxysmal periodic dystonia in infants with 18q23 deletion. This
      study suggests that clustered periodic dystonia should be clinically recognized
      as a phenotypic feature in some patients with 18q23 deletion syndrome.

PMID- 23117894
TI  - Reliable detection of epigenetic histone marks and nuclear proteins in tissue
      cryosections.
AB  - Nuclear processes in real tissues often are significantly different from those in
      cultured cells. However, immunostaining on tissue sections needs long fixation
      which masks antigens and, respectively, antigen retrieval which restores antigen
      accessibility. These treatments affect the immunostaining results and complicate
      their interpretation. The problem is especially significant for nuclear antigens
      which often are very sensitive to both fixation and antigen retrieval. We
      targeted this problem by a study of several histone modifications and nuclear
      proteins in tissue sections of mouse retina which contains cells with both
      conventional and unique inverted nuclei. In the latter, the main chromatin
      classes form separate concentric shells which simplifies evaluation of the signal
      distribution. We show that as a rule, longer fixation demands longer antigen
      retrieval time. Nevertheless, antigens are remarkably diverse in this respect and
      need individual adjustment. We suggest a robust procedure for immunostaining on
      sections, that is, a method that allows controlling the differences in
      immunostaining caused by differences in fixation time and antigen retrieval
      duration, so that immunostaining protocol can be quickly optimized.

PMID- 23117895
TI  - The use of a novel method of endovenous steam ablation in treatment of great
      saphenous vein insufficiency: own experiences.
AB  - OBJECTIVE: Endovascular procedures are gaining more and more popularity as
      treatment of great saphenous vein (GSV) incompetence. The purpose of the present
      study was to assess the efficacy of steam GSV ablation. METHODS: Steam ablation
      using the steam vein sclerosis system (CERMA, France) was performed in 20
      patients with GSV incompetence. The efficacy of the procedure was evaluated using
      ultrasound and the following parameters were assessed: changes in lumen diameter,
      GSV wall thickness, reflux and presence/absence of blood flow. RESULTS: The GSV
      steam ablation resulted in the obliteration of the vein lumen in all patients -
      reflux or blood flow were not observed in any subject. A significant decrease of
      GSV lumen diameter and an increase of GSV wall thickness were also observed in
      all subjects following the procedure. No postoperative complications were noted.
      The steam ablation technique was also positively assessed by the patients.
      CONCLUSIONS: Steam ablation is an endovascular surgical technique, which can
      become popular and widely used due to its efficacy and safety. It is also easy to
      use and patient-friendly. The research on its use should be continued.

PMID- 23117896
TI  - Starburst dendrimers consisting of triphenylamine core and 9-phenylcarbazole
      based dendrons: synthesis and properties.
AB  - Novel dendrimers consisting of a triphenylamine core and 1st to 3rd generations
      of 9-phenylcarbazole-based dendrons were synthesized by Suzuki coupling reaction
      through convergent approach. Their structures were confirmed by two-dimensional
      correlated H-H COSY and C-H HSQC NMR spectra, MALDI-TOF MS and elemental
      analysis. The dendrimers exhibit excellent thermal stability with 5% weight loss
      temperatures over 540  degrees C. The computer modeling reveals that the dendrons
      in dendrimers greatly twisted with the generation, leading to the dendrimers
      decreased crystalline ability. Of interest is the observation that, for an
      identical dendrimer, the solid film displays the similar UV absorption and
      luminescence emission profiles to the solution sample, indicating that, after
      evaporation of solvent, the rigid dendrimer can well maintain its conformational
      morphology and the aggregation or stacking of the chromophoric groups is
      significantly inhibited. All the dendrimers can emit intense fluorescence with
      narrow full width at half maximum (FWHM) around 46-50 nm. Moreover, with the
      incremental generation, the quantum efficiencies remarkably increase from 64 to
      95%, suggesting that the highly contorted and bulky dendrons effectively decrease
      energy wastage and non-radiative decay. The synergistic effect of electron
      donating triphenylamine core and 9-phenylcarbazole-based dendrons results in the
      HOMO energy level of -5.36 eV for the 3rd-generation dendrimer, very close to the
      work function of the ITO/PEDOT electrode (-5.2 eV), which characteristic is very
      advantageous for the hole injection and transport materials.

PMID- 23117898
TI  - Intraoperative soft tissue tension and postoperative range of motion in posterior
      stabilized total knee arthroplasty.
AB  - BACKGROUND: Intraoperative soft tissue tension can significantly impact the range
      of motion following total knee arthroplasty (TKA). However, the level of impact
      remains unclear. The purpose of this study was to investigate the relationship
      between intraoperative soft tissue tension and postoperative range of motion.
      METHODS: This retrospective study included 504 patients operated with posterior
      stabilized TKA. During surgery, we adjusted the soft tissue tension from 80 to
      160 N for both flexion and extension with the tensor/balancer device and torque
      driver. Patients were grouped into three categories based on intraoperative soft
      tissue tension and analyzed with the 1-year postoperative range of motion using
      one-way analysis of variance (ANOVA). In addition, Pearson's correlation
      coefficients were determined to assess the association between intraoperative
      soft tissue tension and postoperative range of motion. RESULTS: The absolute
      tension value at 90 degrees  flexion did not affect the postoperative flexion
      angle (p = 0.61). The absolute tension value at 0 degrees  extension did not
      affect the postoperative extension angle (p = 0.91). Likewise, the difference of
      tension between flexion and extension did not affect the postoperative flexion
      angle (p = 0.86). All comparisons did not have the differences in sex, height,
      weight, body mass index, diagnosis and preoperative range of motion between three
      groups. No significant correlation was found in each comparison (r = 0.078, r =
      0.031, r = -0.052, respectively). CONCLUSIONS: We did not observe a correlation
      between intraoperative soft tissue tension adjusted from 80 to 160 N and 1-year
      postoperative range of motion in posterior stabilized TKA.

PMID- 23117897
TI  - Analysis of cardiopulmonary coupling to assess adaptive servo-ventilation success
      in complex sleep apnea management.
AB  - BACKGROUND: Adaptive servo-ventilation (ASV) is used to treat complex sleep apnea
      syndrome (CompSAS), but with variable success. Factors influencing success are
      poorly understood. ASV devices determine their output based upon characteristics
      of a given breath and on proprietary algorithms that assume a periodic breathing
      pattern. Periodic breathing patterns produce elevated narrow band low-frequency
      cardiopulmonary coupling (eNB-LFC). Therefore, we hypothesized that ASV success
      would correlate with elevated proportions of periodic breathing as marked by eNB
      LFC on cardiopulmonary coupling (CPC) analysis. METHODS: This was a retrospective
      study of 106 consecutive patients presenting to an academic tertiary care sleep
      center with CompSAS between July 2008 and July 2009 who underwent ASV titration
      with polysomnographic signals amenable to CPC analysis. RESULTS: The study
      included 89 males (84 %) and 17 females (16 %), with mean age of 63.3 years.
      Median diagnostic apnea-hypopnea index (AHI) was 38 (21, 56)/h, and on continuous
      positive airway pressure (CPAP), the median residual AHI (CompSAS) was 36.5 (23,
      58)/h, with central apneas occurring on average 22.5 (13, 39)/h. ASV brought AHI
      to 11.0 +/- 13.0, with success in 81.1 % of patients, as defined by an AHI of
      <10/h. NB-LFC was elevated (>0) in 45.3 %; however, the percentage of eNB-LFC did
      not correlate with ASV treatment success (p = 0.518). No clinical factors were
      found to be associated with ASV success. CONCLUSION: ASV was successful in 81 %
      of patients with CompSAS. However, eNB-LFC calculated from CPC, a marker for
      periodic breathing, did not correlate with ASV success and therefore may not be a
      useful tool to predict ASV success.

PMID- 23117899
TI  - The aetiology of total knee arthroplasty failure influences the improvement in
      knee function.
AB  - BACKGROUND: Some indications for revision total knee arthroplasty (TKA), e.g.
      arthrofibrosis, have been identified to yield inferior results. The aim of this
      study was to analyse the results of revision TKA according to aetiology of TKA
      failure. PATIENTS AND METHODS: The results of 97 consecutive revision TKA in 97
      patients stratified according to the aetiology of primary TKA failure
      (periprosthetic infection, aseptic loosening, instability and arthrofibrosis),
      were compared using the Knee Society Score (KSS). The effect of patient age,
      gender, BMI, American Society of Anesthesiologists (ASA) classification, interval
      to revision and the occurrence of complications on the outcome were also
      analysed. RESULTS: After a mean follow-up of 29 months, the KSS had significantly
      improved in all patient groups (p < 0.001). The analysis of variance among
      patient groups depicted no significant differences between preoperative KSS (p =
      0.618) and postoperative KSS (p = 0.915), while the magnitude of pre- to
      postoperative improvement showed significant differences between the groups (p =
      0.006). The aetiology of primary TKA failure had an independent influence on pre-
      to postoperative improvement (p = 0.014). Of the other factors analysed, only the
      ASA classification had an independent impact on postoperative KSS (p = 0.045).
      CONCLUSION: The aetiology of TKA failure has an effect on the improvement in knee
      function from revision TKA. As no difference was observed between patient groups
      postoperatively, similar clinical results can be expected independent of the
      aetiology of primary TKA failure.

PMID- 23117900
TI  - Awakening (mis)conceptions about brain death.

PMID- 23117902
TI  - Psychological symptoms of family members of high-risk intensive care unit
      patients.
AB  - BACKGROUND: Family members of patients in intensive care are at increased risk
      for psychological symptoms. OBJECTIVES: To compare levels of posttraumatic stress
      disorder, anxiety, and depression during and 3 months after the intensive care
      experience in family members of patients at high risk for dying and to determine
      if differences were related to the patient's final disposition. METHODS:
      Longitudinal descriptive study of 41 family members in 3 tertiary care intensive
      care units. RESULTS: By repeated-measures analysis of variance, family members'
      levels of posttraumatic stress disorder were significantly lower (P = .01) at 3
      months after (mean score, 1.27; SD, 0.86) than during (mean, 1.61; SD, 0.81) the
      experience. Mean anxiety and depression scores were significantly lower (P <
      .001) after (anxiety: 7.35; SD, 3.91; depression: 5.63; SD, 4.58) than during
      (anxiety: 11.5; SD, 4.88; depression: 9.51; SD, 4.31) the experience. Scores for
      posttraumatic stress disorder, anxiety, and depression did not differ
      significantly between family members of patients who died and family members of
      patients who survived. Yet, all 13 family members of deceased patients and 42% of
      the total sample of 41 had traumatic stress scores of 1.5 or greater. Among the
      total sample, 44% had significant anxiety, and 27% were depressed. CONCLUSION:
      Family members' symptoms of posttraumatic stress disorder, anxiety, and
      depression significantly decreased 3 months after the intensive care experience
      and did not differ according to the patients' final disposition. However, many
      family members still had significant risk for posttraumatic stress disorder and
      borderline anxiety and depression at 3 months.

PMID- 23117903
TI  - Nurse-led intervention to improve surrogate decision making for patients with
      advanced critical illness.
AB  - BACKGROUND: Problems persist with surrogate decision making in intensive care
      units, leading to distress for surrogates and treatment that may not reflect
      patients' values. OBJECTIVES: To assess the feasibility, acceptability, and
      perceived effectiveness of a multifaceted, nurse-led intervention to improve
      surrogate decision making in intensive care units. STUDY DESIGN: A single-center,
      single-arm, interventional study in which 35 surrogates and 15 physicians
      received the Four Supports Intervention, which involved incorporating a family
      support specialist into the intensive care team. That specialist maintained a
      longitudinal relationship with surrogates and provided emotional support,
      communication support, decision support, and anticipatory grief support. A mixed
      methods approach was used to evaluate the intervention. RESULTS: The intervention
      was implemented successfully in all 15 patients, with a high level of completion
      of each component of the intervention. The family support specialist devoted a
      mean of 48 (SD 36) minutes per day to each clinician-patient-family triad. All
      participants reported that they would recommend the intervention to others. At
      least 90% of physicians and surrogates reported that the intervention (1)
      improved the quality and timeliness of communication, (2) facilitated discussion
      of the patient's values and treatment preferences, and (3) improved the patient
      centeredness of care. CONCLUSIONS: The Four Supports Intervention is feasible,
      acceptable, and was perceived by physicians and surrogates to improve the quality
      of decision making and the patient-centeredness of care. A randomized trial is
      warranted to determine whether the intervention improves patient, family, and
      health system outcomes.

PMID- 23117905
TI  - Building a nursing productivity measure based on the synergy model: first steps.
AB  - BACKGROUND: The Synergy Model describes nurses' work on the basis of the
      individual needs of patients and their families. OBJECTIVE: To generate data
      necessary to develop a nursing productivity system by using the Synergy Model as
      a conceptual framework. METHODS: Nurses from 3 different intensive care units
      participated. In phase 1, charge nurses in focus groups described patient and
      family indicators considered when making nurse-patient assignments. In phase 2,
      charge nurse data were used to construct a survey for experienced staff nurses,
      asking them to link the indicators to 3 levels of nursing workload. RESULTS:
      Thirty charge nurses considered all 8 patient dimensions of the Synergy Model
      when making nurse-patient assignments. Thirty-two experienced staff nurses
      completed 79 surveys ranking patients' stability as the most important dimension
      in patient care followed by complexity and predictability. Respondents linked a
      common set of unique indicators to each of the patient dimensions of the Synergy
      Model: fluctuation in vital signs was linked to stability; number and severity of
      diagnoses, to complexity; trajectory of illness, to predictability; lack of
      reserve, to resiliency; invasiveness of procedures, to vulnerability; family
      educational level and participation style, to family participation in decision
      making/care; and home environment, to resources. Sets of indicators were common
      across units and clustered around level of workload. CONCLUSION: The Synergy
      Model shows promise as a conceptual framework for a nursing productivity system.
      Using a model that centers nursing work on patients' needs may better capture
      what nurses do and enhance our capacity to quantify nursing resource allocation.

PMID- 23117904
TI  - Communication by nurses in the intensive care unit: qualitative analysis of
      domains of patient-centered care.
AB  - BACKGROUND: High-quality communication is a key determinant and facilitator of
      patient-centered care. Nurses engage in most of the communication with patients
      and patients' families in the intensive care unit. OBJECTIVE: To perform a
      qualitative analysis of nurses' communications. METHODS: Ethnographic
      observations of 315 hours of interactions and 53 semistructured interviews with
      33 nurses were conducted in a 26-bed cardiac-medical intensive care unit in an
      academic hospital and a 26-bed general intensive care unit in a Veterans Affairs
      hospital in Portland, Oregon. Communication interactions were categorized into 5
      domains of patient-centered care. Interviews were analyzed to identify major
      themes in nurses' roles and preferences for communicating with patients and
      patients' families within the domains. RESULTS: Most communication occurred in
      the domains of biopsychosocial information exchange, patient as person, and
      clinician as person. Nurses endorsed the importance of the domains of shared
      power and responsibility and therapeutic alliance but had relatively few
      communication interactions in these areas. Communication behaviors were strongly
      influenced by the nurses' roles as translators of information between physicians
      and patients and the patients' families and what the nurses were and were not
      willing to communicate to patients and patients' families. CONCLUSIONS: Critical
      care, including communication, is a collaborative effort. Understanding how
      nurses engage in patient-centered communication in the intensive care unit can
      guide future interventions to improve patient-centered care.

PMID- 23117906
TI  - Cardiac tamponade after removal of temporary pacer wires.
AB  - BACKGROUND: After removal of temporary pacemaker wires, nurses measure vital
      signs frequently to assess for cardiac tamponade; however, evidence for this
      procedure is limited. OBJECTIVES: To determine risk factors for cardiac tamponade
      after temporary pacemaker wire removal. METHODS: Retrospective review of data for
      coronary artery bypass graft and valve surgery (N = 23 717) performed from
      January 1999 to December 2008. Patients were categorized by reason for
      reoperation: bleeding less than 3 days after initial surgery (n = 812, group 1),
      bleeding 3 days or more after index surgery but not for cardiac tamponade (n =
      171, group 2), bleeding 3 days or more after index surgery for cardiac tamponade
      after temporary pacemaker wire removal (n = 23, group 3), and no reoperation (n =
      22 711, group 4). RESULTS: Less than 1% (9.7 cases/10 000) of patients required
      reoperation for cardiac tamponade after removal of temporary pacer wires. Of
      patient-related factors studied, only smoking history differed for group 3 vs
      group 1 (P = .03) and group 2 (P = .01). Of vital sign changes, 1 patient (4%)
      had tachycardia and 3 patients had cardiac arrest, but only 1 of the 3 had
      hypotension before the arrest. In total, 12 patients (52%) had hypotension;
      however, it was mild or intermittent in 5 cases, and did not occur within the 4
      hours after wire removal in 3 cases. After removal of temporary pacing wires,
      common early signs/symptoms were bleeding (26%) and dyspnea (26%). Other
      documented changes were pressure in the chest, diaphoresis, cold and clammy skin,
      dizziness, and mental status changes. CONCLUSIONS: Tamponade related to pacer
      wire removal was rare and not consistently associated with changes in vital
      signs. Dyspnea, bleeding, and other factors may indicate early onset of cardiac
      tamponade after removal of temporary pacer wires.

PMID- 23117908
TI  - Trendelenburg position: "put to bed" or angled toward use in your unit?

PMID- 23117907
TI  - Slim stroke scales for assessing patients with acute stroke: ease of use or loss
      of valuable assessment data?
AB  - BACKGROUND: Scientific guidelines recommend the National Institutes of Health
      Stroke Scale for ischemic stroke assessment. However, many nurses find "slim"
      National Institutes of Health Stroke Scale versions or the Glasgow Coma Scale
      easier to use. OBJECTIVE: To compare 3 "slim" versions of the National Institutes
      of Health Stroke Scale and the Glasgow Coma Scale with the full National
      Institutes of Health Stroke Scale. METHODS: Components of the full National
      Institutes of Health Stroke Scale and Glasgow Coma Scale were abstracted from
      records of consecutive stroke patients. Items were subtracted from the full
      National Institutes of Health Stroke Scale, with items contained in "slim"
      versions retained. False-negative rates for neurological disability were
      calculated for the "slim" versions and the Glasgow Coma Scale. RESULTS: Data were
      collected from 172 acute stroke patients (median [interquartile range] 6 [3-12]
      for National Institutes of Health Stroke Scale, 15 [12-15] for Glasgow Coma
      Scale): 143 (83%) were ischemic stroke patients (27% posterior circulation
      strokes) and 29 (17%) were intracerebral hemorrhage patients. The value of "slim"
      scales and the Glasgow Coma Scale declined in a stepwise manner as the full
      National Institutes of Health Stroke Scale decreased because of false-negative
      results despite the presence of a measurable disabling deficit. False-negative
      rates were 5% to 19% on "slim" versions and 56% with the Glasgow Coma Scale.
      CONCLUSIONS: Use of "slim" scales, and in particular the Glasgow Coma Scale,
      substantially decreases the value of a structured neurological assessment,
      particularly in patients with low National Institutes of Health Stroke Scale
      scores.

PMID- 23117909
TI  - Sudden shortness of breath and anxiety.

PMID- 23117910
TI  - Dexmedetomidine to treat lisdexamfetamine overdose and serotonin toxidrome in a 6
      year-old girl.
AB  - A 6-year-old girl displayed symptoms of serotonin syndrome after accidental
      ingestion of Vyvanse (lisdexamfetamine dimesylate). Dexmedetomidine was
      administered because of persistent neuromuscular hyperactivity and severe
      agitation despite initial therapy with benzodiazepines. Some children show a
      paradoxical reaction to benzodiazepines, and dexmedetomidine has a possible role
      in the treatment of serotonin syndrome.

PMID- 23117911
TI  - Diagnosing ventilator-associated pneumonia in critically ill patients with
      sepsis.
AB  - BACKGROUND: Timely diagnosis and prognostic assessment of ventilator-associated
      pneumonia remain major challenges in critical care. OBJECTIVE: To explore the
      value of soluble triggering receptor expressed on myeloid cells 1, procalcitonin,
      and the Clinical Pulmonary Infection Score in the diagnosis and prognostic
      assessment of ventilator-associated pneumonia. METHODS: For 92 patients,
      bronchoalveolar lavage fluid was cultured for detection of microorganisms, serum
      levels of the receptor and procalcitonin and levels of the receptor in exhaled
      ventilator condensate were measured, and the Clinical Pulmonary Infection Score
      was calculated. RESULTS: On the day of diagnosis, patients who had pneumonia had
      higher serum levels of the receptor, procalcitonin, and C-reactive protein;
      higher white blood cell counts; and higher pulmonary infection and Sequential
      Organ Failure Assessment scores than did patients without pneumonia. White blood
      cell count (odds ratio, 1.118; 95% CI, 1.139-1.204) and serum levels of the
      receptor (odds ratio, 1.002; 95% CI, 1.000-1.005) may be risk factors for VAP.
      Serum levels of the receptor plus the pulmonary infection score were the most
      reliable for diagnosis; the area under the receiver operating characteristic
      curve was 0.972 (95% CI, 0.945-0.999), sensitivity was 0.875, and specificity was
      0.95. For 28-day survival, procalcitonin level combined with pulmonary infection
      score was the most reliable for prognostic assessment (area under the curve,
      0.848; 95% CI, 0.672-1.025). CONCLUSIONS: In patients with ventilator-associated
      pneumonia, serum levels of the receptor plus the pulmonary infection score are
      useful for diagnosis, and procalcitonin levels plus the pulmonary infection score
      are useful for prognostic assessment.

PMID- 23117912
TI  - Patients' characteristics associated with readmission to a surgical intensive
      care unit.
AB  - BACKGROUND: Readmission within 48 hours is a leading performance indicator of the
      quality of care in an intensive care unit. OBJECTIVE: To investigate variables
      that might be associated with readmission to a surgical intensive care unit.
      METHODS: Demographic characteristics, severity-of-illness scores, and survival
      rates were collected for all patients admitted to a surgical intensive care unit
      between 1995 and 2000. Long-term survival and quality of life were determined for
      patients who were readmitted within 30 days after discharge from the unit.
      Quality of life was measured with the EuroQol-6D questionnaire. Multivariate
      logistic analysis was used to calculate the independent association of expected
      covariates. RESULTS: Mean follow-up time was 8 years. Of the 1682 patients alive
      at discharge, 141 (8%) were readmitted. The main causes of readmission were
      respiratory decompensation (48%) and cardiac conditions (16%). Compared with the
      total sample, patients readmitted were older, mostly had vascular (39%) or
      gastrointestinal (26%) disease, and had significantly higher initial severity of
      illness (P = .003, .007) and significantly more comorbid conditions (P = .005).
      For all surgical classifications except general surgery, readmission was
      independently associated with type of admission and need for mechanical
      ventilation. Long-term mortality was higher among patients who were readmitted
      than among the total sample. Nevertheless, quality-of-life scores were the same
      for patients who were readmitted and patients who were not. CONCLUSION: The
      adverse effect of readmission to the intensive care unit on survival appears to
      be long-lasting, and predictors of readmission are scarce.

PMID- 23117913
TI  - Investigation of the correlation between norepinephrine transporter gene
      polymorphisms and essential hypertension.
AB  - Essential hypertension (EH) is an etiological risk factor that poses a serious
      threat to human health. The aim of this study therefore was to investigate the
      correlation between the two SNPs (rs1805067 and rs2397771) of the norepinephrine
      (NE) transporter gene in the sympathetic nervous system and essential
      hypertension (EH). A total of 96 hypertensive patients (EH group) and 96 normal
      subjects (control group) were selected by epidemiological investigation and the
      sequences at rs1805067 and rs2397771 in the two groups were investigated using
      polymerase chain reaction (PCR) and Sanger sequencing. In the EH group, systolic
      and diastolic blood pressure, body mass index (BMI), levels of creatinine, low
      density lipoprotein cholesterol (LDL-C), triglycerides (TG), and the percentage
      of drinkers were found to be higher compared with those of the control group
      (P<0.05). The results of the analysis of the allele frequencies of rs1805067
      (A/G) revealed that there was no difference between the two groups (P>0.05). The
      analysis results of the allele frequencies of rs2397771 (C/G) in the EH group
      revealed that G accounted for 48.96% and C for 51.04% of the patients, while in
      the control group, these values were 64.58 and 35.42%, respectively. These
      results indicated a significant difference between the two groups (P<0.05). In
      the population studied, the onset of EH may be correlated with BMI, TG, LDL-C and
      high-density lipoprotein cholesterol (HDL-C). EH may be related to the rs2397771
      (C/G) C allele polymorphism of the NE transporter gene but not to rs1805067
      (A/G). 

PMID- 23117920
TI  - Prognostic factors of acute partial transverse myelitis.

PMID- 23117914
TI  - Expanding the yeast prion world: Active prion conversion of non
      glutamine/asparagine-rich Mod5 for cell survival.
AB  - Mammalian and fungal prion proteins form self-perpetuating beta-sheet-rich
      fibrillar aggregates called amyloid. Prion inheritance is based on propagation of
      the regularly oriented amyloid structures of the prion proteins. All yeast prion
      proteins identified thus far contain aggregation-prone glutamine/asparagine
      (Gln/Asn)-rich domains, although the mammalian prion protein and fungal prion
      protein HET-s do not contain such sequences. In order to fill this gap, we
      searched for novel yeast prion proteins lacking Gln/Asn-rich domains via a genome
      wide screen based on cross-seeding between two heterologous proteins and
      identified Mod5, a yeast tRNA isopentenyltransferase, as a novel non-Gln/Asn-rich
      yeast prion protein. Mod5 formed self-propagating amyloid fibers in vitro and the
      introduction of Mod5 amyloids into non-prion yeast induced dominantly and
      cytoplasmically heritable prion state [MOD (+) ], which harbors aggregates of
      endogenous Mod5. [MOD (+) ] yeast showed an increased level of membrane lipid
      ergosterol and acquired resistance to antifungal agents. Importantly, enhanced de
      novo formation of [MOD (+) ] was observed when non-prion yeast was grown under
      selective pressures from antifungal drugs. Our findings expand the family of
      yeast prions to non-Gln/Asn-rich proteins and reveal the acquisition of a fitness
      advantage for cell survival through active prion conversion.

PMID- 23117922
TI  - Spinocerebellar ataxia types 2 and 10: more than a coincidental association?

PMID- 23117924
TI  - Plasma anti-amyloid-beta autoantibodies in all Alzheimer disease types.

PMID- 23117926
TI  - The evolution of neurology.

PMID- 23117927
TI  - Prayer beliefs and change in life satisfaction over time.
AB  - A considerable number of studies have focused on the relationship between prayer,
      health, and well-being. But the influence of some types of prayer (e.g.,
      petitionary prayer) has received more attention than others. The purpose of this
      study is to examine an overlooked aspect of prayer: trust-based prayer beliefs.
      People with this orientation believe that God knows that best way to answer a
      prayer and He selects the best time to provide an answer. Three main findings
      emerge from data that were provided by a nationwide longitudinal survey of older
      people reveals. First, the results reveal that Conservative Protestants are more
      likely to endorse trust-based prayer beliefs. Second, the findings suggest that
      these prayer beliefs tend to be reinforced through prayer groups and informal
      support from fellow church members. Third, the data indicate that stronger trust
      based prayer beliefs are associated with a greater sense of life satisfaction
      over time.

PMID- 23117928
TI  - Polydopamine spheres as active templates for convenient synthesis of various
      nanostructures.
AB  - In this work, monodisperse polydopamine (PDA) spheres with tunable diameters have
      been synthesized through a facile and low cost method using a deionized water and
      alcohol mixed solvent. The PDA spheres possess surface functional groups (-OH, 
      NH(2)), exhibiting an extraordinary versatile active nature. It is demonstrated
      that the PDA spheres could serve as an active template for the convenient
      synthesis of various nanostructures, e.g., MnO(2) hollow spheres or PDA/Fe(3)O(4)
      and PDA/Ag core/shell nanostructures. No surface modification or special
      treatment is required for the synthesis of these nanostructures, which makes the
      fabrication process simple and very convenient. The novel application of
      PDA/Fe(3)O(4) spheres as fillers in nanocomposites for high-performance
      capacitors is demonstrated, indicating a promising practicality. The PDA spheres
      provide a new general platform not only for the facile assembly of nanostructures
      but also a green synthetic template for practical applications.

PMID- 23117929
TI  - Autophagy activity is up-regulated in adipose tissue of obese individuals and
      modulates proinflammatory cytokine expression.
AB  - Autophagy, an evolutionary conserved process aimed at recycling damaged
      organelles and protein aggregates in the cell, also modulates proinflammatory
      cytokine production in peripheral blood mononuclear cells. Because adipose tissue
      inflammation accompanied by elevated levels of proinflammatory cytokines is
      characteristic for the development of obesity, we hypothesized that modulation of
      autophagy alters adipose tissue inflammatory gene expression and secretion. We
      tested our hypothesis using ex vivo and in vivo studies of human and mouse
      adipose tissue. Levels of the autophagy marker LC3 were elevated in sc adipose
      tissue of obese vs. lean human subjects and positively correlated to both
      systemic insulin resistance and morphological characteristics of adipose tissue
      inflammation. Similarly, autophagic activity levels were increased in adipose
      tissue of obese and insulin resistant animals as compared with lean mice.
      Inhibition of autophagy by 3-methylalanine in human and mouse adipose tissue
      explants led to a significant increase in IL-1beta, IL-6, and IL-8 mRNA
      expression and protein secretion. Noticeably, the enhancement in IL-1beta, IL-6,
      and keratinocyte-derived chemoattractant (KC) by inhibition of autophagy was more
      robust in the presence of obesity. Similar results were obtained by blocking
      autophagy using small interfering RNA targeted to ATG7 in human Simpson-Golabi
      Behmel syndrome adipocytes. Our results demonstrate that autophagy activity is up
      regulated in the adipose tissue of obese individuals and inhibition of autophagy
      enhances proinflammatory gene expression both in adipocytes and adipose tissue
      explants. Autophagy may function to dampen inflammatory gene expression and
      thereby limit excessive inflammation in adipose tissue during obesity.

PMID- 23117930
TI  - Short-term pharmacological suppression of the hyperprolactinemia of infertile hCG
      overproducing female mice persistently restores their fertility.
AB  - Female infertility is often associated with deregulation of hormonal networks,
      and hyperprolactinemia is one of the most common endocrine disorders of the
      hypothalamic-pituitary axis affecting the reproductive functions. We have shown
      previously that transgenic female mice overexpressing human chorionic
      gonadotropin beta-subunit (hCGbeta+ mice), and producing elevated levels of
      bioactive LH/hCG, exhibit increased production of testosterone and progesterone,
      are overweight and infertile, and develop hyperprolactinemia associated with
      pituitary lactotrope adenomas in adult age. In the present study, we analyzed the
      influence of the hyperprolactinemia of hCGbeta+ females on their reproductive
      phenotype by treating them with the dopamine agonists, bromocriptine and
      cabergoline. Long-term bromocriptine treatment of adult mice was effective in the
      control of obesity, pituitary growth, and disturbances in the hormone profile,
      demonstrating that hyperprolactinemia was the main cause of the hCGbeta+ female
      phenotype. Interestingly, short-term treatment (1 wk) with cabergoline applied on
      5-wk-old mice corrected hyperprolactinemia, hyperandrogenism, and
      hyperprogesteronemia, prevented pituitary overgrowth, normalized gonadal
      function, and recovered fertility of adult hCGbeta+ females after hormone-induced
      and natural ovulation. The same cabergoline treatment in the short term applied
      on 3-month-old hCGbeta+ females failed to recover their reproductive function.
      Hence, we demonstrated that the short-term cabergoline treatment applied at a
      critical early stage of the phenotype progression effectively prevented the
      hyperprolactinemia-associated reproductive dysfunction of hCG-overproducing
      females.

PMID- 23117932
TI  - Corticotropin-releasing factor receptor binding in the amygdala changes across
      puberty in a sex-specific manner.
AB  - Corticotropin-releasing factor receptors type 1 (CRF(1)) and type 2 (CRF(2)) have
      complementary roles in controlling the hypothalamic-pituitary-adrenal (HPA) axis.
      Because CRF receptors are expressed in sex steroid-sensitive areas of the
      forebrain, they may contribute to sex-specific patterns of stress sensitivity and
      susceptibility to stress-related mood disorders, which are more frequent in
      women. To determine whether CRF receptors vary as a function of age and/or sex,
      we measured receptor binding in the amygdala of male and female, prepubertal and
      adult rats. Both receptor subtypes demonstrated age- and sex-specific binding
      patterns. In the basolateral amygdala and posteroventral medial amygdala, CRF(1)
      binding decreased in males and increased in females after puberty, there, CRF(2)
      binding increased in males and was unchanged in females. In the posterodorsal
      medial amygdala, CRF(1) binding was unchanged across puberty, whereas CRF(2)
      binding increased across puberty far more in males than in females. Binding was
      lowest overall in the central amygdala; there, CRF(1) was unchanged while CRF(2)
      binding increased across puberty only in males. Thus, in all four examined areas
      across prepuberty to adulthood, CRF(2) binding increased far more in males than
      in females and resulted in significantly more binding in adult males than in
      adult females. These sex-specific developmental patterns are consistent with sex
      differences in hypothalamic-pituitary-adrenal responsiveness and may thus
      contribute to sex differences in mood disorder susceptibility.

PMID- 23117931
TI  - The androgen metabolite, 5alpha-androstane-3beta,17beta-diol, decreases cytokine
      induced cyclooxygenase-2, vascular cell adhesion molecule-1 expression, and P
      glycoprotein expression in male human brain microvascular endothelial cells.
AB  - P-glycoprotein (Pgp), a multiple drug resistance transporter expressed by
      vascular endothelial cells, is a key component of the blood-brain barrier and has
      been shown to increase after inflammation. The nonaromatizable androgen,
      dihydrotestosterone (DHT), decreases inflammatory markers in vascular smooth
      muscle cells, independent of androgen receptor (AR) stimulation. The principal
      metabolite of DHT, 5alpha-androstane-3beta,17beta-diol (3beta-diol), activates
      estrogen receptor (ER)beta and similarly decreases inflammatory markers in
      vascular cells. Therefore, we tested the hypothesis that either DHT or 3beta-diol
      decrease cytokine-induced proinflammatory mediators, vascular cell adhesion
      molecule-1 (VCAM-1) and cyclooxygenase-2 (COX-2), to regulate Pgp expression in
      male primary human brain microvascular endothelial cells (HBMECs). Using RT-qPCR,
      the mRNAs for AR, ERalpha, and ERbeta and steroid metabolizing enzymes necessary
      for DHT conversion to 3beta-diol were detected in male HBMECs demonstrating that
      the enzymes and receptors for production of and responsiveness to 3beta-diol are
      present. Western analysis showed that 3beta-diol reduced COX-2 and Pgp
      expression; the effect on Pgp was inhibited by the ER antagonist, ICI-182,780. IL
      1beta-caused an increase in COX-2 and VCAM-1 that was reduced by either DHT or
      3beta-diol. 3beta-diol also decreased cytokine-induced Pgp expression. ICI
      182,780 blocked the effect of 3beta-diol on COX-2 and VCAM-1, but not Pgp
      expression. Therefore, in cytokine-stimulated male HBMECs, the effect of 3beta
      diol on proinflammatory mediator expression is ER dependent, whereas its effect
      on Pgp expression is ER independent. These studies suggest a novel role of 3beta
      diol in regulating blood-brain barrier function and support the concept that
      3beta-diol can be protective against proinflammatory mediator stimulation.

PMID- 23117933
TI  - Activin signaling regulates Sertoli cell differentiation and function.
AB  - Throughout development, activin A signaling stimulates proliferation and inhibits
      differentiation of testicular Sertoli cells. A decline in activin levels at
      puberty corresponds with the differentiation of Sertoli cells that is required to
      sustain spermatogenesis. In this study, we consider whether terminally
      differentiated Sertoli cells can revert to a functionally immature phenotype in
      response to activin A. To increase systemic activin levels, the right tibialis
      anterior muscle of 7-wk-old C57BL/6J mice was transduced with an adeno-associated
      virus (rAAV6) expressing activin A. We show that chronic activin signaling
      reduces testis mass by 23.5% compared with control animals and induces a
      hypospermatogenic phenotype, consistent with a failure of Sertoli cells to
      support spermatogenesis. We use permeability tracers and transepithelial
      electrical resistance measurements to demonstrate that activin potently disrupts
      blood-testis-barrier function in adult mice and ablates tight junction formation
      in differentiated primary Sertoli cells, respectively. Furthermore, increased
      activin signaling reinitiates a program of cellular proliferation in primary
      Sertoli cells as determined by 5-ethynyl-2'-deoxyuridine incorporation.
      Proliferative cells reexpress juvenile markers, including cytokeratin-18, and
      suppress mature markers, including claudin-11. Thus, activin A is the first
      identified factor capable of reprogramming Sertoli cells to an immature,
      dedifferentiated phenotype. This study indicates that activin signaling must be
      strictly controlled in the adult in order to maintain Sertoli cell function in
      spermatogenesis.

PMID- 23117934
TI  - Phloroglucinol protects small intestines of mice from ionizing radiation by
      regulating apoptosis-related molecules: a comparative immunohistochemical study.
AB  - Phloroglucinol (PG) is a phenolic compound isolated from Ecklonia cava, a brown
      algae abundant on Jeju island, Korea. Previous reports have suggested that PG
      exerts antioxidative and cytoprotective effects against oxidative stress. In this
      study, we confirmed that PG protected against small intestinal damage caused by
      ionizing radiation, and we investigated its protective mechanism in detail.
      Regeneration of intestinal crypts in the PG-treated irradiated group was
      significantly promoted compared with that in irradiated controls. The expression
      level of proapoptotic molecules such as p53, Bax, and Bak in the small intestine
      was downregulated and that of antiapoptotic molecules such as Bcl-2 and Bcl
      X(S/L) was augmented in the PG-treated group. On histological observation of the
      small intestine, PG inhibited the immunoreactivity of p53, Bax, and Bak and
      increased that of Bcl-2 and Bcl-X(S/L). These results demonstrate the protective
      mechanisms of PG in mice against intestinal damage from ionizing radiation,
      providing the benefit of raising the apoptosis threshold of jejunal crypt cells.

PMID- 23117935
TI  - Relation between ultrastructural localization, changes in caveolin-1, and
      capillarization of liver sinusoidal endothelial cells in human hepatitis C
      related cirrhotic liver.
AB  - Most vascular endothelial cells are continuously exposed to shear stress in vivo.
      Caveolae are omega-shaped membrane invaginations in endothelial cells (ECs) and
      are enriched in cholesterol, caveolins, and signaling molecules. This study was
      designed to elucidate the ultrastructural localization and change in caveolin-1
      expression within human liver sinusoidal endothelial cells (LSECs) during the
      progression of cirrhosis caused by hepatitis C, using tissue sections prepared
      via perfusion-fixation. Normal control liver specimens and hepatitis C-related
      Child-Pugh A and C cirrhotic liver specimens were studied. Caveolin-1 in the
      liver sinusoids was examined via immunohistochemistry, Western blotting, and
      immunoelectron microscopy. In control liver tissue, caveolin-1 was localized on
      caveolae mainly in arterial and portal endothelial cells of the portal tract and
      was also found on vesicles and some fenestrae in LSECs around the central vein.
      In cirrhotic liver tissue, aberrant caveolin-1 expression was observed on
      caveolae-like structures in LSECs. Caveolin-1 was especially overexpressed in
      late-stage cirrhosis. This study demonstrates that caveolin-1 is strongly
      expressed within caveolae-like structures and associated vesicles within LSECs of
      the hepatitis C-related cirrhotic liver. These findings suggest a direct
      association of caveolin-1 in the process of differentiation of LSECs in cirrhosis
      mediated capillarization.

PMID- 23117936
TI  - Obstructive sleep apnea in patients with typical atrial flutter: prevalence and
      impact on arrhythmia control outcome.
AB  - BACKGROUND: The clinical yield of cavotricuspid isthmus (CTI) radiofrequency
      ablation of atrial flutter (AF) is limited by a high incidence of atrial
      fibrillation (AFib) in the long term. Among other acknowledged variables, the
      association of obstructive sleep apnea (OSA) could favor incomplete arrhythmia
      control in this setting. We assessed the impact of CPAP in reducing the
      occurrence of AFib after CTI ablation. METHODS: Consecutive patients with AF who
      were undergoing CTI ablation were screened for OSA. Relationship of the following
      variables with the occurrence of AFib during follow-up (12 months) was
      investigated: CPAP initiation, hypertension, BMI, underlying structural heart
      disease, left atrial diameter, and AFib documentation prior to ablation. RESULTS:
      We prospectively included 56 patients (mean age: 66 (+/- 11) years; 12 female
      patients), of whom 46 (82%) had OSA and 25 (45%) had severe OSA. Twenty-one
      patients (38%) had AFib during follow-up after CTI ablation. Both freedom from
      AFib prior to ablation and CPAP initiation in those patients without previously
      documented AFib at inclusion were associated with a reduction of AFib episodes
      during follow-up (P = .019 and P = .025, respectively). Inversely, CPAP was not
      protective from AFib recurrence when this arrhythmia was documented prior to
      ablation (P = .25). CONCLUSIONS: OSA is a prevalent condition in patients with
      AF. Treatment with CPAP is associated with a lower incidence of newly diagnosed
      AFib after CTI ablation. Screening for OSA in patients with AF appears to be a
      reasonable clinical strategy.

PMID- 23117937
TI  - Challenges experienced by paid peer providers in mental health recovery: a
      qualitative study.
AB  - Peer providers are increasingly employed in mental health services. We explored
      challenges experienced by 31 peer providers in diverse settings and roles using
      in-depth interviews, as part of a larger study focusing on their recovery (Moran
      et al. in Qual Health Res, 2012). A grounded theory approach revealed three
      challenge domains: work environment, occupational path, and personal mental
      health. Challenges in the work environment differed between conventional mental
      health settings and consumer-run agencies. Occupational domain challenges
      included lack of clear job descriptions, lack of skills for using one's life
      story and lived experience, lack of helping skills, and negative aspects of
      carrying a peer provider label. Personal mental health challenges included
      overwork and symptom recurrence. Implications for all domains are discussed, with
      focus on training and skill development. 

PMID- 23117938
TI  - Computational model for estimating the short- and long-term cardiac response to
      arteriovenous fistula creation for hemodialysis.
AB  - Creation of an arteriovenous fistula (AVF) for hemodialysis may result in cardiac
      failure due to dramatic increases in cardiac output. To investigate the
      quantitative relations between AVF flow, changes in cardiac output, myocardial
      stress and strain and resulting left ventricular adaptation, a computational
      model is developed. The model combines a one-dimensional pulse wave propagation
      model of the arterial network with a zero-dimensional one-fiber model of cardiac
      mechanics and includes adaptation rules to capture the effect of the baro-reflex
      and long-term structural remodelling of the left ventricle. Using generic
      vascular and cardiac parameters based on literature, simulations are done that
      illustrate the model's ability to quantitatively reproduce the clinically
      observed increase in brachial flow and cardiac output as well as occurence of
      eccentric hypertrophy. Patient-specific clinical data is needed to investigate
      the value of the computational model for personalized predictions.

PMID- 23117940
TI  - Neuromuscular therapy from bench to bedside.

PMID- 23117941
TI  - Amyotrophic lateral sclerosis: drug therapy from the bench to the bedside.
AB  - Amyotrophic lateral sclerosis (ALS) is an unrelenting progressive
      neurodegenerative disease causing progressive weakness, ultimately leading to
      death. Despite aggressive research, the pathways leading to neuronal death are
      incompletely understood. Riluzole is the only drug clinically proven to enhance
      survival of ALS patients, but its mechanism of action is not clearly understood.
      In this article, the proposed pathophysiology of ALS is reviewed including
      glutamate excitotoxicity, oxidative stress, mitochondrial dysfunction, autoimmune
      mechanisms, protein aggregation, SOD1 accumulation, and neuronal death. Based on
      these mechanisms, past major ALS drug studies will be reviewed as well as
      promising current ALS drug studies, focusing on the advancement of these studies
      from the bench to the patient's bedside.

PMID- 23117942
TI  - Guillain-Barre syndrome.
AB  - Guillain-Barre syndrome (GBS) is an acute inflammatory polyradiculoneuropathy,
      which has various clinical presentations and both axonal and demyelinating forms.
      The original description of "ascending paralysis" encompasses the most common
      varieties: the primary demyelinating form, acute inflammatory demyelinating
      polyneuropathy (AIDP), and some of the axonal forms, acute motor axonal
      neuropathy (AMAN) and acute motor and sensory axonal neuropathy (AMSAN). However,
      there are now well-documented acute "monophasic" polyneuropathies that have a
      different clinical phenomenology than that described originally by Guillain,
      Barre, and Strohl: Miller Fisher syndrome, pure sensory neuropathy/neuronopathy,
      pandysautonomia, and oropharyngeal variant. Here the authors review both typical
      GBS (AIDP, AMAN, and AMSAN), and variant syndromes with a focus on clinical and
      diagnostic features, pathologic findings, pathogenesis, and treatment.

PMID- 23117944
TI  - The diabetic neuropathies: practical and rational therapy.
AB  - Diabetes is associated with a variety of chronic and acute neuropathies. In this
      article, the authors summarize the clinical features of the most common diabetic
      neuropathies, focusing on those for which therapy is available or under active
      investigation. Distal symmetric polyneuropathy (DSP) is the most common form.
      Potential treatments for DSP are discussed in four broad themes: (1) medication
      and lifestyle therapy to improve hyperglycemia, insulin resistance, and attendant
      features of metabolic syndrome, including obesity and dyslipidemia; (2)
      pharmacologic therapy to alter neuropathy natural history aimed at rational
      targets from known pathophysiology; (3) symptomatic relief of neuropathic pain;
      and (4) treatment to prevent complications of neuropathy, including stasis ulcers
      and falls. The approach to the most common acute diabetic neuropathies is also
      reviewed.

PMID- 23117943
TI  - Chronic inflammatory demyelinating polyradiculoneuropathy: from bench to bedside.
AB  - Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is the most
      common treatable chronic autoimmune neuropathy. Multiple diagnostic criteria have
      been established, with the primary goal of identifying neurophysiologic hallmarks
      of acquired demyelination. Treatment modalities have expanded to include numerous
      immunomodulatory therapies, although the best evidence continues to be for
      corticosteroids, plasma exchange, and intravenous immunoglobulin (IVIg). This
      review describes the pathology, epidemiology, pathogenesis, diagnosis, and
      treatment of CIDP.

PMID- 23117945
TI  - Inherited neuropathies.
AB  - With a prevalence of 1 in 2500 people, inherited peripheral nerve diseases,
      collectively called Charcot-Marie-Tooth disease (CMT), are among the most common
      inherited neurologic disorders. Patients with CMT typically present with chronic
      muscle weakness and atrophy in limbs, sensory loss in the feet and hands, and
      foot deformities. Clinical similarities between patients often require genetic
      testing to achieve a precise diagnosis. In this article, the author reviews the
      clinical and pathologic features of CMT, and demonstrates how electrodiagnostic
      and genetic tools are used to assist in the diagnosis and symptomatic management
      of the diseases. Several cases are presented to illustrate the diagnostic
      processes.

PMID- 23117946
TI  - Myasthenia gravis.
AB  - Myasthenia gravis (MG) is the most common disorder of the neuromuscular junction
      (NMJ), with an estimated prevalence between 25 and 142 per million. It
      characteristically presents with fatigable weakness, often initially involving
      the ocular muscles and manifesting as intermittent ptosis and diplopia.
      Ultimately, the disease generalizes in two-thirds of patients, leading to
      weakness of bulbar, neck, limb, and respiratory muscles. The majority of patients
      with generalized MG, and roughly half of patients with purely ocular disease,
      harbor antibodies to skeletal muscle nicotinic acetylcholine receptors. A subset
      of patients with generalized disease have antibodies to muscle-specific receptor
      tyrosine kinase (MuSK). Acetylcholinesterase inhibitors are often the first
      modality of therapy for MG. As an immune-mediated disorder, MG can respond to
      several immunosuppressive agents, such as corticosteroids, azathioprine,
      mycophenolate mofetil, and cyclosporin. Thymectomy is a key component of
      management in appropriately chosen MG patients and those with thymoma. Newer or
      alternative immunotherapies including tacrolimus, rituximab, methotrexate, and
      complement inhibiting agents are an area of active investigation.

PMID- 23117949
TI  - Myotonic dystrophy: from bench to bedside.
AB  - Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are autosomal dominant disorders
      classically characterized by muscle weakness, myotonia, and early-onset
      cataracts. Patients may also experience dysfunction of the heart, brain,
      gastrointestinal, endocrine, skin, and respiratory systems. The pathogenesis of
      myotonic dystrophy is related to trinucleotide (DM1) and tetranucleotide (DM2)
      repeat expansions that produce toxic mutant mRNA with subsequent interference of
      RNA-splicing mechanisms. Optimal disease management includes symptomatic care,
      screens for asymptomatic disease, counseling, and a multidisciplinary approach.
      The authors review the pathogenesis, clinical features, diagnostic tests, and
      standard management of DM1 and DM2 and outline promising clinical research for
      patients with these disorders.

PMID- 23117948
TI  - Inclusion body myositis.
AB  - The idiopathic inflammatory myopathies are a group of rare disorders that share
      many similarities. These include dermatomyositis (DM), polymyositis (PM),
      necrotizing myopathy (NM), and sporadic inclusion body myositis (IBM). Inclusion
      body myositis is the most common idiopathic inflammatory myopathy after age 50
      and it presents with chronic proximal leg and distal arm asymmetric mucle
      weakness. Despite similarities with PM, it is likely that IBM is primarily a
      degenerative disorder rather than an inflammatory muscle disease. Inclusion body
      myositis is associated with a modest degree of creatine kinase (CK) elevation and
      an abnormal electromyogram demonstrating an irritative myopathy with some
      chronicity. The muscle histopathology demonstrates inflammatory exudates
      surrounding and invading nonnecrotic muscle fibers often times accompanied by
      rimmed vacuoles. In this chapter, we review sporadic IBM. We also examine past,
      essentially negative, clinical trials in IBM and review ongoing clinical trials.
      For further details on DM, PM, and NM, the reader is referred to the idiopathic
      inflammatory myopathies chapter.

PMID- 23117947
TI  - Idiopathic inflammatory myopathies.
AB  - The idiopathic inflammatory myopathies are a group of rare disorders including
      polymyositis (PM), dermatomyositis (DM), and autoimmune necrotizing myopathies
      (NMs). The idiopathic inflammatory myopathies share many similarities. They
      present acutely, subacutely, or chronically with marked proximal and symmetric
      muscle weakness, except for associated distal and asymmetric weakness in
      inclusion body myositis. The idiopathic inflammatory myopathies also share a
      variable degree of creatine kinase (CK) elevation and a nonspecifically abnormal
      electromyogram demonstrating an irritative myopathy. The muscle pathology
      demonstrates inflammatory exudates of variable distribution within the muscle
      fascicle. Despite these similarities, the idiopathic inflammatory myopathies are
      a heterogeneous group. The overlap syndrome (OS) refers to the association of PM,
      DM, or NM with connective tissue disease, such as scleroderma or systemic lupus
      erythematosus. In addition to elevated antinuclear antibodies (ANA), patients
      with OS may be weaker in the proximal arms than the legs mimicking the pattern
      seen in some muscular dystrophies. In this review, we focus on DM, PM, and NM and
      examine current and promising therapies.

PMID- 23117950
TI  - The muscular dystrophies.
AB  - The muscular dystrophies are disorders of progressive muscular degeneration and
      weakness. As a group they display clinical heterogeneity that reflects the
      heterogeneity of molecular mechanisms responsible for them, and range from
      congenital to adulthood onset. Recent advances in the field include improved
      methods of diagnosis, continued identification of disease genes, and the
      development of a unified model of pathogenesis in facioscapulohumeral dystrophy.
      These advances are reflected in the development of new therapeutic approaches,
      some of which have already led to clinical trials in the dystrophinopathies and
      limb-girdle dystrophies.

PMID- 23117951
TI  - Neuropathic pain therapy: from bench to bedside.
AB  - Neuropathic pain is a result of complex interactions between peripheral and
      central mechanisms with multiple potential therapeutic targets. However, the
      complexity of these mechanisms and relative youth of translational pain research,
      which is in its infancy, have prevented translation of successful basic bench
      research to human therapy. Most of the clinically available neuropathic pain
      treatments are borrowed from other therapeutic areas, such as antidepressants and
      antiepileptics, or involve application of older therapy, such as opioids.
      Exceptions are ziconotide, tapentadol, and the high-concentration capsaicin
      patch. Similar to all other analgesic agents, these provide only partial pain
      relief in subsets of patients. The standard of care for patients with chronic
      neuropathic pain is multimodal and multidisciplinary. For most patients to
      achieve and maintain satisfactory pain relief a combination of therapeutic agents
      is necessary, providing the empiric basis for rational polypharmacy, which has
      become a standard approach as well.

PMID- 23117952
TI  - Maternal protein restriction in rats leads to reduced PGC-1alpha expression via
      altered DNA methylation in skeletal muscle.
AB  - Intrauterine growth retardation (IUGR) is thought to program insulin resistance,
      type 2 diabetes and other metabolic diseases in later life. Skeletal muscle is an
      important tissue involved in regulating the metabolism. We therefore hypothesized
      that the regulation of glucose- and lipid-related genes in skeletal muscle may
      contribute to metabolic changes in rats with IUGR. In this study, IUGR rats were
      bred from pregnant rats fed a protein-restricted (PR) diet. Insulin resistance
      (IR)-related metabolic parameters and the expression of key regulatory IR genes
      such as peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator
      1alpha (PGC-1alpha) and glucose transporter 4 (GLUT4) were measured in skeletal
      muscle from 18-month-old female IUGR rats. The methylation status of promoters of
      PGC-1alpha and GLUT4 were assessed in the same tissues. During the aging process,
      IUGR rats exhibited catch-up growth and obesity. In old age, they showed impaired
      glucose tolerance demonstrated by high glucose and insulin AUC (area under the
      curve) values. The expression of glucose transporter 4 (GLUT4) and PGC-1alpha in
      skeletal muscle was significantly reduced in IUGR rats. Mean CpG island
      methylation in the PGC-1alpha promoter sequence was significantly increased.
      These results suggest that a PR diet during gestation may induce epigenetic
      changes, such as DNA methylation, in the promoters of specific genes. The changes
      may affect gene expression and account for the metabolic alterations in female
      rats with IUGR. 

PMID- 23117953
TI  - Strategies to address weight-based victimization: youths' preferred support
      interventions from classmates, teachers, and parents.
AB  - Weight-Based Victimization is a frequent experience for adolescents who are
      overweight or obese, and is associated with numerous psychosocial and physical
      consequences for those who are targets of victimization. Assessing targets'
      preferences for different types of support and intervention has been absent in
      the context of weight-based victimization, but is needed to help inform potential
      interventions, motivate action, and identify strategies to help adolescents cope
      with experiences of weight-related teasing or bullying. Adolescents (14-18 years,
      N = 361, 40 % female, 71 % Caucasian) enrolled in national weight-loss camps
      completed an on-line survey. Participants who reported previous experiences of
      weight-based victimization were surveyed about their preferred interventions from
      peers, friends, teachers, Physical Education (PE) teachers/coaches, and parents.
      Participants indicated their preferences for specific strategies pertaining to
      target support, bullying intervention and prevention (e.g., inclusion in peer
      activities, confronting the bully, telling an adult, and improving anti-bullying
      policies). Friends (66 %) and peers (58 %) were the most highly preferred
      intervention agents followed by teachers (55 %), PE teachers/coaches (44 %), and
      parents (43 %). Participants who experienced more weight-based victimization
      expressed increased desire for intervention. The frequency of victimization,
      social support from friends and family, and perceived likelihood and helpfulness
      of intervention significantly influenced participant preferences for certain
      types of intervention, although preferences were generally consistent across
      participants' characteristics. The current study is the first to document youth's
      preferences for interventions in response to weight-based victimization. The
      findings have important implications for encouraging appropriate intervention and
      informing bystanders, which may help to reduce the prevalence, recurrence, and
      consequences for youth who are targets of weight-based teasing or bullying.

PMID- 23117954
TI  - Water-dispersible fullerene aggregates as a targeted anticancer prodrug with both
      chemo- and photodynamic therapeutic actions.
AB  - Prodrug therapy is one strategy to deliver anticancer drugs in a less reactive
      manner to reduce nonspecific cytotoxicity. A new multifunctional anticancer
      prodrug system based on water-dispersible fullerene (C60) aggregates is
      introduced; this prodrug system demonstrates active targeting, pH-responsive
      chemotherapy, and photodynamic therapeutic (PDT) properties. Incorporating (via a
      cleavable bond) an anticancer drug, which is doxorubicin (DOX) in this study, and
      a targeting ligand (folic acid) onto fullerene while maintaining an overall size
      of approximately 135 nm produces a more specific anticancer prodrug. This prodrug
      can enter folate receptor (FR)-positive cancer cells and kill the cells via
      intracellular release of the active drug form. Moreover, the fullerene aggregate
      carrier exhibits PDT action; the cytotoxicity of the system towards FR-positive
      cancer cells is increased in response to light irradiation. As the DOX drug
      molecules are conjugated onto fullerene, the DOX fluorescence is significantly
      quenched by the strong electron-accepting capability of fullerene. The
      fluorescence restores upon release from fullerene, so this fluorescence quenching
      restoring feature can be used to track intracellular DOX release. The combined
      effect of chemotherapy and PDT increases the therapeutic efficacy of the DOX
      fullerene aggregate prodrug. This study provides useful insights into designing
      and improving the applicability of fullerene for other targeted cancer prodrug
      systems.

PMID- 23117956
TI  - Acute febrile illness in cirrhosis - thinking beyond spontaneous bacterial
      peritonitis!
AB  - The aim of this study was to look at the aetiological factors presenting as acute
      febrile illness in cirrhotic patients. The study group included all cirrhotic
      patients admitted as inpatients between January and December 2011 with a history
      of fever of less than seven days duration. Detailed history, clinical examination
      and investigations, as required, were noted. The data collected were analysed. A
      total of 42 patients formed the study group. The male-to-female ratio was 9.5:1.
      The mean age at presentation was 45.09 years (24-77 years). The aetiological
      factors for fever were: spontaneous bacterial peritonitis (20), lower respiratory
      tract infection (8), urinary tract infection (6), lower limb cellulitis (4),
      acute cholecystitis (2) and malaria (2). The mean MELD (model for end-stage liver
      disease) score at presentation was 20.4. Three patients with spontaneous
      bacterial peritonitis (SBP) and a mean MELD score of 31 died during the hospital
      admission. Febrile illness in cirrhosis is attributable to multiple causes.
      Outcome is dependent on the severity of underlying liver disease.

PMID- 23117955
TI  - Use of an electronic health record clinical decision support tool to improve
      antibiotic prescribing for acute respiratory infections: the ABX-TRIP study.
AB  - BACKGROUND: Antibiotics are often inappropriately prescribed for acute
      respiratory infections (ARIs). OBJECTIVE: To assess the impact of a clinical
      decision support system (CDSS) on antibiotic prescribing for ARIs. DESIGN: A two
      phase, 27-month demonstration project. SETTING: Nine primary care practices in
      PPRNet, a practice-based research network whose members use a common electronic
      health record (EHR). PARTICIPANTS: Thirty-nine providers were included in the
      project. INTERVENTION: A CDSS was designed as an EHR progress note template. To
      facilitate CDSS implementation, each practice participated in two to three site
      visits, sent representatives to two project meetings, and received quarterly
      performance reports on antibiotic prescribing for ARIs. MAIN OUTCOME MEASURES: 1)
      Use of antibiotics for inappropriate indications. 2) Use of broad spectrum
      antibiotics when inappropriate. 3) Use of antibiotics for sinusitis and
      bronchitis. KEY RESULTS: The CDSS was used 38,592 times during the 27-month
      intervention; its use was sustained for the study duration. Use of antibiotics
      for encounters at which diagnoses for which antibiotics are rarely appropriate
      did not significantly change through the course of the study (estimated 27-month
      change, 1.57% [95% CI, -5.35%, 8.49%] in adults and -1.89% [95% CI, -9.03%,
      5.26%] in children). However, use of broad spectrum antibiotics for ARI
      encounters improved significantly (estimated 27 month change, -16.30%, [95% CI, 
      24.81%, -7.79%] in adults and -16.30 [95%CI, -23.29%, -9.31%] in children).
      Prescribing for bronchitis did not change significantly, but use of broad
      spectrum antibiotics for sinusitis declined. CONCLUSIONS: This multi-method
      intervention appears to have had a sustained impact on reducing the use of broad
      spectrum antibiotics for ARIs. This intervention shows promise for promoting
      judicious antibiotic use in primary care.

PMID- 23117957
TI  - Improving case fatality rate of adult tetanus in urban Nigeria: focus on better
      facilities of care.
AB  - Tetanus is a life threatening preventable infection with a high mortality. Our
      aim was to determine the current case fatality rate at our centre in a
      retrospective case review of patients aged > 10 years who had been hospitalized
      with tetanus between August 2006 and July 2011. We show the intrahospital case
      fatality rate. Data are based on 176 cases for which we had sufficient
      information. There was a preponderance of males (3.09:1); 167 (95%) had
      generalized tetanus and nine (5%) had localized tetanus. The overall case
      fatality rate was 56.2% and was higher in males (64.4%) than females (27.9%; P =
      0.0001). In a multivariate analysis, older age (P = 0.000), male gender (P =
      0.005) and a longer duration of admission (P = 0.004) were significant
      determinants of outcome. The case fatality rate of tetanus has declined at our
      centre from 70% between January 2004 and March 2006 to 56.2% currently. Improved
      facilities are required in order to significantly reduce adverse outcome from
      tetanus.

PMID- 23117958
TI  - [Early cutaneous carcinogenesis in organ transplant patients].

PMID- 23117960
TI  - [What is your diagnosis? Hydrocarbon pneumonitis with right pneumothorax after
      petroleum aspiration (fire eater's lung)].

PMID- 23117961
TI  - [Prevalence and symptoms of vitamin D deficiency in general practices].
AB  - In 776 primary care patients serum vitamin D level was measured in month of
      september showing deficiency (<50 nmol/l) in 45,1%, severe deficiency (<30
      nmol/l) in 9,8% and serum levels below the recommended target level of 75 nmol/l
      in 88,9% of cases. Three possible symptoms of vitamin D deficiency were assessed
      by a visual analogue scale (0-10): fatigue, muscle weakness, and muscle and joint
      pain. A significant correlation between muscle weakness and degree of vitamin D
      deficiency was shown (p=0,04), whereas there was no correlation in the two other
      symptoms. However, patients with vitamin D deficiency more frequently reported
      fatigue (p=0,02) and muscle weakness (p=0,009) than patients without deficiency
      did, and no difference was seen concerning muscle and joint pain.

PMID- 23117962
TI  - [Treatment of metastatic melanoma: are we entering the era of targeted
      treatment?].
AB  - The treatment of metastatic melanoma has progressed greatly during the last two
      years. Nowadays melanomas can be divided into molecular subgroups, this being
      therapeutically relevant. Around 60% of  melanomas show a BRAF mutation and can
      be treated with selected tyrokinase inhibitors. In addition a CTLA-4-antibody was
      developed which shuts off the natural immune breaking system resulting in a
      continuous anti-tumor reaction. Angiogenesis inhibitors have shown there
      importance in different phase II trials. We hope that this represents only the
      first step of an individualized treatment for metastatic melanoma.

PMID- 23117963
TI  - [The infected diabetic foot].
AB  - Disorders of local immunity associated with diabetes, neuropathy, vascular
      disease and pressure lesions all contribute to the pathogenesis of diabetic foot
      lesions. Diabetic foot infections are frequently encountered, comprising
      multifactorial pathology and high morbidity and mortality rates. Microbiological
      sampling is indicated only when infection is suspected clinically, that is, when
      a lesion presents a minimum of two of the following six signs: erythema, heat,
      pain, tumefaction, induration or purulent discharge.

PMID- 23117964
TI  - [Herpes simplex encephalitis].

PMID- 23117965
TI  - [A 58-year-old soldier with a history of weight loss and exercise intolerance.
      Giant cell arteritis].
AB  - We report the case of a 58-years-old soldier with a history of movement related
      neck pain, weight loss and exercise intolerance. Blood tests presented signs of
      an inflammatory syndrome. The CT-scan showed extended thickening of the aortic
      wall characteristic for aortitis. The diagnosis of giant cell arteritis could be
      histologically confirmed by biopsy of the temporal arteries. Our case report
      emphasizes the importance of the various imaging modalities. We discuss the
      different forms of disease evolution and the treatment regimen.

PMID- 23117966
TI  - [Youth does not protect against stroke: what hormonal contraception contributes
      to risk].

PMID- 23117967
TI  - [Additional benefits of inhalation therapy with two bronchodilators with
      different mechanisms of action].

PMID- 23117971
TI  - Observational prospective cohort study of patients with newly-diagnosed ocular
      sebaceous carcinoma.
AB  - PURPOSE: To investigate the epidemiology and clinicopathological management for
      ocular sebaceous carcinoma (OSC) in the UK. METHODS: Observational prospective
      cohort study of patients with newly-diagnosed OSC. The British Ophthalmological
      Surveillance Unit captured incident cases of OSC between 2008 and 2010. Incident
      and 6-month follow-up questionnaires from reporting ophthalmologists captured OSC
      demographic and clinical data. RESULTS: Data were available on 51 patients with
      unilateral OSC (response rate 85%). The UK estimated annual incidence was 0.41
      cases per million population (95% CI 0.31 to 0.54). Median age was 70 years (SD
      14, range 28-98) with 57% women. OSC location was upper lid (54%), lower lid
      (20%), multicentric (14%) and caruncle (12%). Most common misdiagnoses included
      chalazion (42%), basal cell carcinoma (30%) and blepharoconjunctivitis (16%),
      with median delay in diagnosis of 10 months (SD 9, range 0.5-36). Specialist
      ophthalmic pathologists performed diagnostics in 62%, with
      pagetoid/intraepithelial spread present in 39%. Misdiagnosis of chalazion
      (p=0.019) and pagetoid tumour spread (p=0.016) was associated with a significant
      diagnostic delay (one-way ANOVA/R(2)). Primary surgical management involved
      excision with reconstruction (49%), primary exenteration (10%) and Mohs surgery
      (8%). There were three deaths (out of 51) during the study period; one patient
      died of OSC-related disease and the other two due to other causes. CONCLUSIONS:
      This population-based prospective study confirms OSC as a rare cancer in the UK.
      Masquerade syndromes result in significant diagnostic delays and increase the
      risk of pagetoid tumour spread. There is considerable UK variation in
      pathological and surgical management, and ocular reconstruction and radical
      surgery is often required for OSC due to delayed presentation.

PMID- 23117972
TI  - MRI findings at baseline and after neoadjuvant chemotherapy in orbital
      retinoblastoma (IRSS stage III).
AB  - BACKGROUND: Published findings on MRI results in retinoblastoma patients treated
      with neoadjuvant chemotherapy (NACT) are lacking. The present study evaluates the
      role of MRI in International Retinoblastoma Staging System (IRSS) stage III
      retinoblastoma treated with NACT. METHODS: 28 consecutive IRSS stage III
      retinoblastoma patients underwent MRI at baseline and after three cycles of NACT
      prior to enucleation. MRI films were reviewed retrospectively by an ophthalmic
      radiologist who was masked to patient outcome. Optic nerves were staged based on
      their thickness, contrast enhancement and length of involvement on MRI. Response
      evaluation criteria were based on optic nerve staging and changes in the size of
      the orbital mass on MRI after NACT. RESULTS: The proposed staging at baseline and
      after NACT was able to predict event-free-survival (EFS) (p=0.005 and p <0.001,
      respectively) and overall survival (OS) (p=0.002 and p=0.001, respectively) using
      the log-rank test for trends. Patients with complete or partial response
      according to the proposed response evaluation criteria had significantly better
      EFS (p<0.001) and OS (p=0.024) than those who had stable or progressive disease.
      CONCLUSIONS: The proposed MRI based optic nerve staging system and response
      evaluation criteria were able to predict EFS and OS at baseline and after NACT.

PMID- 23117973
TI  - Letter to "Mapping of ghrelin gene expression and cell distribution in the
      stomach of morbidly obese patients--a possible guide for efficient sleeve
      gastrectomy construction" Obesity Surgery (2012) 22:617-622. doi:10.1007/s11695
      011-0585-9.

PMID- 23117974
TI  - A repeated halving approach to fabricate ultrathin single-walled carbon nanotube
      films for transparent supercapacitors.
AB  - Ultrathin SWCNT transparent and conductive films on flexible and transparent
      substrates are prepared via repeatedly halving the directly grown SWCNT films and
      flexible and transparent supercapacitors with excellent performance were
      fabricated.

PMID- 23117975
TI  - Is Cheyne-Stokes respiration friend or foe of heart failure?

PMID- 23117977
TI  - The COPD control panel: towards personalised medicine in COPD.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous
      disease whose assessment and management have traditionally been based on the
      severity of airflow limitation (forced expiratory volume in 1 s (FEV1)). Yet, it
      is now clear that FEV1 alone cannot describe the complexity of the disease. In
      fact, the recently released Global Initiative for Chronic Obstructive Lung
      Disease (GOLD), 2011 revision has proposed a new combined assessment method using
      three variables (symptoms, airflow limitation and exacerbations). METHODS: Here,
      we go one step further and propose that in the near future physicians will need a
      'control panel' for the assessment and optimal management of individual patients
      with complex diseases, including COPD, that provides a path towards personalised
      medicine. RESULTS: We propose that such a 'COPD control panel' should include at
      least three different domains of the disease: severity, activity and impact. Each
      of these domains presents information on different 'elements' of the disease with
      potential prognostic value and/or with specific therapeutic requirements. All
      this information can be easily incorporated into an 'app' for daily use in
      clinical practice. CONCLUSION: We recognise that this preliminary proposal needs
      debate, validation and evolution (eg, including 'omics' and molecular imaging
      information in the future), but we hope that it may stimulate debate and research
      in the field.

PMID- 23117979
TI  - Multiple-breath washout measurements can be significantly shortened in children.
AB  - Multiple-breath washout (MBW)-derived lung clearance index (LCI) is a sensitive
      measure of ventilation inhomogeneity in patients with cystic fibrosis (CF), but
      LCI measurement is time consuming. We systematically assessed ways to shorten LCI
      measurements. In 68 school-aged children (44 with mild CF lung disease) three
      standard nitrogen (N2) MBWs were applied. We assessed repeatability and
      diagnostic performance of (1) LCI measured earlier from three MBW runs and (2)
      LCI measured at complete MBW (1/40th of starting N2 concentration) from two runs
      only. Compared with the standard LCI from three complete MBW runs, the new LCI
      based on three N2MBW runs until 1/20th, or two complete runs until 1/40th,
      provided similar or better repeatability as well as sensitivity and specificity
      for CF lung disease. Alternative ways to measure LCI reduced test duration in
      children with CF by 30% and 41%, respectively. LCI measurements can be reliably
      shortened in children. These new MBW protocols may advance the transition of LCI
      from research into clinical settings.

PMID- 23117982
TI  - Focal pulmonary oedema: an unusual presentation of acute mitral regurgitation.

PMID- 23117984
TI  - Comparison of stem morphology and anatomy of two alfalfa clonal lines exhibiting
      divergent cell wall composition.
AB  - BACKGROUND: In previous research, two alfalfa clonal lines (252 and 1283) were
      identified that exhibited environmentally stable differences in stem cell walls.
      Compared with stems of 1283, stems of 252 have a higher cell wall concentration
      and greater amounts of lignin and cellulose but reduced levels of pectic sugar
      residues. These results suggest greater deposition of secondary xylem and a
      reduction in pith in stems of 252 compared with 1283. RESULTS: The stem
      morphology and anatomy of first-cut and second-cut harvests of field-grown 1283
      and 252 were examined. For both harvests, stems of 1283 were thicker and had a
      higher leaf/stem ratio compared with stems of 252. Stem cross-sections of both
      genotypes were stained for lignin, and the proportions of stem area that were
      pith and secondary xylem were measured using ImageJ. Stems of 252 exhibited
      greater deposition of secondary xylem and a reduction in pith proportion compared
      with stems of 1283 for the first-cut harvest, but this difference was not
      statistically significant for the second-cut harvest. CONCLUSION: The results
      indicate that the proportions of secondary xylem and pith are not environmentally
      stable in these two genotypes and hence cannot be the sole basis for the
      differences in cell wall concentration/composition.

PMID- 23117985
TI  - Neurotropic infectious agents and cognitive impairment in schizophrenia.
AB  - The links between infectious agents and risk for schizophrenia have been widely
      debated, but few investigations have focused on "epidiagnostic" effects, eg,
      whether exposures to infectious agents alter key clinical aspects of the
      disorder, such as cognitive impairment. The present theme issue evaluates
      epidiagnostic cognitive effects of two common infectious agents, namely Herpes
      Simplex Virus, type 1 and Toxoplasma gondii.

PMID- 23117986
TI  - Teach them to be self-aware.

PMID- 23117980
TI  - Risk of tuberculosis following HIV seroconversion in high-income countries.
AB  - BACKGROUND: Few data exist on tuberculosis (TB) incidence according to time from
      HIV seroconversion in high-income countries and whether rates following
      initiation of a combination of antiretroviral treatments (cARTs) differ from
      those soon after seroconversion. METHODS: Data on individuals with well estimated
      dates of HIV seroconversion were used to analyse post-seroconversion TB rates,
      ending at the earliest of 1 January 1997, death or last clinic visit. TB rates
      were also estimated following cART initiation, ending at the earliest of death or
      last clinic visit. Poisson models were used to examine the effect of current and
      past level of immunosuppression on TB risk after cART initiation. RESULTS: Of 19
      815 individuals at risk during 1982-1996, TB incidence increased from 5.89/1000
      person-years (PY) (95% CI 3.77 to 8.76) in the first year after seroconversion to
      10.56 (4.83 to 20.04, p=0.01) at 10 years. Among 11 178 TB-free individuals
      initiating cART, the TB rate in the first year after cART initiation was
      4.23/1000 PY (3.07 to 5.71) and dropped thereafter, remaining constant from year
      2 onwards averaging at 1.64/1000 PY (1.29 to 2.05). Current CD4 count was
      inversely associated with TB rates, while nadir CD4 count was not associated with
      TB rates after adjustment for current CD4 count, HIV-RNA at cART initiation.
      CONCLUSIONS: TB risk increases with duration of HIV infection in the absence of
      cART. Following cART initiation, TB incidence rates were lower than levels
      immediately following seroconversion. Implementation of current recommendations
      to prevent TB in early HIV infection could be beneficial.

PMID- 23117987
TI  - Expression and function of ferroportin 1 in O-2A progenitor cells.
AB  - Iron plays a crucial role in the survival, differentiation, and myelin formation
      of oligodendrocyte lineages. However, the regulation mechanism of iron
      homeostasis in oligodendrocytes remains unclear. Recently, much research has
      focused on Ferroportin 1 (FPN1), an iron exporter protein. First, about 95% pure
      primary rat O-2A progenitor cells were obtained by shaking methods in our
      laboratory. The expression of FPN1 mRNA and protein in O-2A progenitor cells were
      determined by reverse transcription-PCR and western blot. In addition, the
      localization of FPN1 at the cell membrane, in the cytoplasm and in processes was
      assayed by double-labeling immunofluorescence. A time-dependent increase of iron
      efflux from O-2A progenitor cells was confirmed by the calcein-indicated iron
      efflux assay. However, the same cells treated with FPN1 antibody showed no
      obvious change in iron release. For further confirmation, overexpression of FPN1
      in O-2A progenitor cells was transduced with lentivirus. The release of iron in O
      2A progenitor cells was dramatically increased by the overexpressed FPN1 when
      compared with that of the control group. Both ferritin (Ft) and transferrin
      receptor (TfR) are routinely used as indicators of labile iron pool. Cells
      pretreated with FPN1 antibody upregulated Ft and downregulated TfR protein level,
      while the opposite results occurred in the FPN1 overexpressing cells.
      Determination of Ft and TfR indirectly indicated that FPN1 might contribute to
      iron release from O-2A progenitor cells. We suggested that expression of FPN1 in
      O-2A progenitor cells might play a critical role in iron efflux from these cells.

PMID- 23117988
TI  - [First cases of besnoitiosis in cattle in Switzerland].
AB  - Bovine besnoitiosis has been diagnosed in neighboring countries but not in
      Switzerland so far. This disease occurs endemically in France and focal outbreaks
      have been reported in Germany and Italy. To determine if Besnoitia besnoiti is
      introduced into Switzerland through the import of breeding cattle from France, a
      systematic serological survey was performed. A total of 412 breeding cattle (from
      114 farms) imported from France into Switzerland between 2005 and 2011, were
      serologically examined for antibodies against B. besnoiti using a commercial
      ELISA kit (PrioCHECK(c) Besnoitia Ab 2.0, Prionics AG, Zurich, Switzerland).
      Sixty-four (15.5 %) animals reacted positive in ELISA. The serologic diagnosis
      was confirmed by an indirect immunfluorescence test (IFAT) and a Western blot
      (WB) in only 2 Limousin cows imported from France on a farm in Eastern
      Switzerland. Subsequently, this whole herd (n = 16) was examined clinically and
      serologically and 2 additional Limousin cows imported from Germany also reacted
      positive in the three serological tests. One of these cows presented B. besnoiti
      tissue cysts in the scleral conjunctiva and typical skin lesions in the head
      region. The infection was further confirmed cytologically, histopathologically
      and by PCR. It can be concluded that the parasite is most likely being introduced
      into Switzerland through the import of infected animals.

PMID- 23117989
TI  - Discovery of extended-spectrum beta-lactamase producing Escherichia coli among
      hunted deer, chamois and ibex.
AB  - The aim of the present study was to assess for the first time the dissemination
      of extended-spectrum beta-lactamase (ESBL) producing Escherichia coli in the wild
      animal ecosystem in Switzerland. Fecal samples of 84 red deer, 64 roe deer, 64
      chamois, and 27 ibex were investigated. One sample from a roe deer tested
      positive for ESBL-producing E. coli. The isolate harboured blaCTX-M-1 and tested
      negative for both blaTEM and blaSHV. Based on these results low occurrence of
      ESBL-producing Enterobacteriaceae in the wild animal ecosystem in Switzerland
      must currently be postulated. Further studies are necessary to assess future
      trends.

PMID- 23117990
TI  - [Evaluation of serum cobalamin concentration in cats with clinical signs of
      gastrointestinal disease].
AB  - Medical records of 261 cats presenting with gastrointestinal disease that had a
      serum cobalamin concentration measured were reviewed. In addition, a reference
      range for cobalamin (305 - 1.967ng/L) was established using 22 healthy adult cats
      with undetectable levels of urinary methylmalonic acid. A total of 108 of 261
      cats (41.4 %) had hypocobalaminemia; 69 cats (26.4 %) had cobalamin
      concentrations below the detection limit of the assay (< 150ng/L, group A) and 39
      (15 %) had concentrations between 150 - 304ng/L (group B). The remaining 153
      (58.6 %) cats had normal cobalamin concentrations (group C). Diarrhea was the
      most common clinical sign in hypocobalaminemic cats and vomiting or anorexia was
      the most common sign in normocobalaminemic cats. Only cats with both, vomiting
      and diarrhea were more likely to have hypocobalaminemia than cats with other
      clinical signs (odds ratio, 2.879; 95 % CI, 1.313 - 6.310). Serum cobalamin
      concentration was negatively correlated with age of the patient and positively
      correlated with body condition score. Cats of group A had a significantly higher
      neutrophil count (p = 0.0009) and higher MCV (p = 0.0064) and significantly lower
      hematocrit (p = 0.0018) and albumin concentration (p = 0.0037) than cats in other
      groups. There was no difference between cats of groups B and C with respect to
      complete blood cell counts and metabolic profiles. Among the diagnoses made in
      125 cats (A 69.6 %, B 59 %, C 35.3 %), lymphoma and inflammatory enteropathy were
      most common. Lymphoma was diagnosed in 31.2 % (A 53.8 %, B 15.4 %, C 30.8 %) and
      inflammatory enteropathy in 22.4 % (A 35.7 %, B 7.1 %, C 57.2 %) of cats.
      Hypocobalaminemia is a frequent problem in cats with gastrointestinal disease.
      Presenting clinical signs as well as laboratory results may already indicate its
      probability and severity. However, only values below the detection limit of the
      assay seem to affect routine bloodwork results. Cobalamin should be routinely
      measured in feline gastrointestinal disease, as its serum concentration may
      influence the choice of further diagnostics.

PMID- 23117991
TI  - The use of a slow release GnRH-agonist implant in female ferrets in season for
      oestrus suppression.
AB  - The jill is a long-day breeder with a constant oestrus without mating. Persistent
      oestrogen production results in clinical signs of hyperoestrogenism including
      pancytopenia and death if untreated. As spaying is thought to be related to the
      development of hyperadrenocorticism, a non-invasive, safe and effective long-term
      treatment is needed for oestrus suppression in jills. Seven jills in oestrus were
      treated with a 4.7mg deslorelin implant. Blood samples for estradiol-17beta (E2)
      and progesterone (P4) determination were obtained before as well as 4 and 8 weeks
      after treatment; data are given as geometric mean (deviation factor, DF). Mean E2
      was 280.2 pmol/L (1.7) before, 36.4 pmol/L (1.4) 4 and 21.6 pmol/L (1.1) 8 weeks
      after treatment (p < 0.0001). P4 before treatment was 1.4 nmol/L (2.6), 57.8
      nmol/L (1.9) on week 4 and 3.8 nmol/L (2.6) on week 8 (p < 0.0001) indicating
      ovulation had occurred after implant insertion. Oestrous signs within the
      observation period of up to 32 months remained suppressed.

PMID- 23117992
TI  - [National control of animal epidemics: current status and use of bulk tank milk
      diagnostics].

PMID- 23117996
TI  - Fragmentation of poly(lactic acid) nanosheets and patchwork treatment for burn
      wounds.
AB  - Freestanding poly(L-lactic acid) (PLLA) nanosheets are mass-produced by a simple
      combination of a spin-coating-assisted multi-layering process and a peeling
      technique. The resulting PLLA nanosheets are fragmented by homogenization and
      then reconstructed into a "patchwork" sheet on various surfaces without any
      adhesive reagents. The patchwork is shown to offer excellent protection against
      burn wound infection with Pseudomonas aeruginosa, and may therefore be an
      alternative to conventional burn therapy for prevention of infection.

PMID- 23117997
TI  - Morphological variation of primary reproductive structures in males of five
      families of neotropical bats.
AB  - Bats present unique features among mammals with respect to reproduction, and
      although neotropical bats do not have a hibernation period, many of their
      reproductive characteristics vary seasonally and interspecifically. Thus, this
      work aimed to examine the reproductive structures of 18 species belonging to five
      families of Brazilian bats. The gross anatomy of the testes varied little;
      however, the epididymis of Emballonuridae and Vespertilionidae showed exceptional
      structures with a large elongation of the caudal region. We observed a wide
      variation in the positioning of the testes: Phyllostomidae and Noctilionidae
      presented external testes; Emballonuridae and Molossidae presented migratory
      testes that may be in intra-abdominal or external positions; and Vespertilionidae
      displayed scrotal testes. In the histological evaluation, we observed a different
      pattern in vespertilionid species, with testicular regression and sperm
      retention/storage in the cauda epididymis in the five species analyzed. Similar
      testicular regression was observed in Molossops temminckii; however, sperm
      retention/storage was not observed in this species. These data suggest that
      although the species analyzed are tropical species that do not present a
      prolonged period of torpor (hibernation), they still maintain a period of
      seminiferous tubule regression and sperm storage very similar to that observed in
      hibernating bats.

PMID- 23117998
TI  - Phase separation and bulk p-n transition in single crystals of Bi2Te2Se
      topological insulator.

PMID- 23118000
TI  - Sub-5 nm Ln3+-doped BaLuF5 nanocrystals: a platform to realize upconversion via
      interparticle energy transfer (IPET).

PMID- 23117999
TI  - Examining market trends in the United States smokeless tobacco use: 2005-2011.
AB  - BACKGROUND: While cigarette consumption in the USA continues to decline,
      promotion for and consumption of smokeless tobacco (SLT) is growing. However,
      little research has explored what product features are driving SLT growth,
      despite awareness that product-level factors may be important in SLT use. This
      study analyses national sales data to better understand the impact of product
      features on SLT sales. METHODS: Data on sales of SLT in US convenience stores
      from 2005 to 2011 were obtained from Nielsen Research Company. Each listed
      product was coded for attributes such as type, brand, flavouring and form to
      calculate their respective total sales, market share and contribution to overall
      SLT growth. RESULTS: Sales of moist snuff products (including snus) increased by
      65.6% between 2005 and 2011. Sales of pouched and flavoured forms of moist snuff
      increased by 333.8% and 72.1%, respectively, and contributed to 28% and 59.4% of
      the total growth in the moist snuff category, respectively. Value/discount brands
      accounted for 42% of moist snuff sales in 2011 among the top 10 selling brands,
      largely driven by Grizzly. After 2 years on the national market, Camel Snus was
      also one of the top 10 selling moist snuff brands. CONCLUSIONS: Sales of moist
      snuff, both overall and for particular styles, are increasing. Growing pouch use
      may be attributed to new SLT users, which may include cigarette smokers using
      them as starter SLT products. Increased sales of flavoured and discounted snuff
      raise concerns about use and appeal to youth. Continued surveillance of SLT sales
      trends is warranted.

PMID- 23118001
TI  - Implantable cardioverter defibrillator outcome: beyond ejection fraction?

PMID- 23118002
TI  - Modern-day patient challenge: manage cardiac disease, accept devices, and
      minimize distress.

PMID- 23118003
TI  - Ivabradine for the prevention of inappropriate shocks due to sinus tachycardia in
      patients with an implanted cardioverter defibrillator.
AB  - AIMS: Ivabradine is a specific blocker of the pacemaker current (I(f)) used to
      decrease the sinus rate. Several clinical trials have shown that it is
      beneficial, with or without concomitant beta-blocker therapy, in patients with
      stable angina or heart failure. We sought to take advantage of ivabradine's
      ability to decrease the maximal obtainable sinus rate in order to prevent
      inappropriate shocks due to sinus tachycardia in patients with an implanted
      cardioverter defibrillator (ICD). METHODS AND RESULTS: Prospective open-label
      series including all our patients with an implanted ICD who, during the course of
      2010-2011, received ivabradine with the only purpose of preventing inappropriate
      ICD shocks for sinus tachycardia. These are patients who received one or more
      inappropriate shocks for sinus tachycardia or were conceived to be at very high
      risk for developing such complication. Our series includes five patients who
      received ivabradine (5-10 mg/day) in addition to their usual beta-blocker
      therapy. During a follow-up of 14 months no inappropriate shocks due to sinus
      tachycardia were recorded. CONCLUSION: It is sensible to recommend ivabradine for
      the prevention of inappropriate ICD shocks due to sinus tachycardia in carefully
      selected patients.

PMID- 23118004
TI  - Detection of high incidence of Riata lead breaches by systematic postero-anterior
      and lateral chest X-ray in a large cohort.
AB  - AIMS: Insulation breaches with externalization of conductor cables have been
      described for St-Jude Medical RiataTM defibrillation leads. Published data on the
      incidence of Riata lead abnormalities are quite heterogeneous. The objective of
      this study was to estimate systematically the prevalence of lead abnormalities
      using a postero-anterior (PA) and lateral chest X-ray (CXR). METHODS AND RESULTS:
      From 2002 to 2008, 552 Riata defibrillation leads were implanted at our centre.
      We evaluated patients for potential insulation breaches. A PA and lateral CXR was
      obtained. Chest X-rays were reviewed by two electrophysiologists using a zooming
      function with magnification up to factor 7.5 and were classified as normal or
      abnormal for the presence of conductor externalization. A total of 284 patients
      were included. Riata lead models were 1570, 1580, 1582, 1590, 1592, 7000, 7002,
      and 7022. The total frequency of radiological lead defects was 24.3%. Insulation
      breaches occurred at zones of major lead curvature. Mean maximal spacing between
      extruding lead components was 3.6 +/- 1.9 mm (range 2.0-12.4). Abnormal CXRs were
      more frequent in 8F leads (31.4% vs. 6.3%; P < 0.001). Most defects occurred with
      lead models 1582 (41.2%) and 1580 (31.4%). Mean time since implantation was
      longer in abnormal leads (6.7 vs. 5.9 years; P < 0.001). Abnormal leads had
      higher pacing thresholds (1.1 +/- 0.8 V vs. 0.9 +/- 0.4 V; P = 0.02). CONCLUSION:
      The incidence of insulation breach in Riata leads is much higher than quoted by
      the manufacturer or reported by most of the literature. A PA and lateral CXR with
      zooming appears adequate to identify lead breaches when reviewed by an
      electrophysiologist. Riata lead breaches without electrical abnormalities present
      a management dilemma and will require further studies.

PMID- 23118005
TI  - Remote follow-up of pacemakers in a selected population of debilitated elderly
      patients.
AB  - AIMS: The majority of patients with pacemakers are very elderly, many being >85
      years old. They often suffer from serious illnesses and have great difficulty in
      walking. The aim of our study was to compare remote pacemaker monitoring with in
      home checks of pacemakers, in terms of applicability, efficacy, and cost in a
      selected population of debilitated elderly patients. METHODS AND RESULTS: We
      selected 72 subjects (mean age 87 +/- 8 years) among elderly debilitated patients
      with Medtronic pacemakers, compatible with the Carelink((r)) remote monitoring
      system (13 patients with DDD pacemaker; 59 patients with single-lead VDD
      pacemaker). Remote follow-up was compared with in-home checks performed by nurses
      in 326 patients in similar clinical conditions. A total of 190 transmissions were
      received by remote monitoring (mean transmissions per month: 7.0; mean per
      patient: 2.6; range 1-6) during 27 months of follow-up. In this period, seven
      pacemakers were replaced owing to battery exhaustion, after a mean of 6.7 years
      from implantation. The occurrence of atrial or ventricular high-rate episodes was
      reported in 98 transmissions (53%). Nineteen patients died (annual mortality:
      11.7%). On comparing the costs borne by the hospital for in-home checks, both for
      medical personnel and transportation, the estimated average saving was ?32 per
      year per patient. CONCLUSION: Our study shows that the remote follow-up of
      pacemakers is a reliable, effective, and cost-saving procedure in elderly,
      debilitated patients. Moreover, remote controls provided an accurate and early
      diagnosis of arrhythmia occurrence.

PMID- 23118006
TI  - Facilitating assessment of QT interval duration during ventricular pacing.
AB  - AIMS: We aimed to facilitate the assessment of the QT interval duration during
      conventional right ventricular pacing (VP) by uncovering relationships with the
      underlying QT interval during intrinsic atrioventricular conduction (IC). METHODS
      AND RESULTS: The study patients (n = 122, age 68 +/- 11 years) were dual-chamber
      device recipients with preserved IC and narrow QRS complexes. Patients were
      classified into either 'normal-QT' (n = 70) or 'prolonged-QT' (n = 52) group.
      Incremental atrial pacing rates were exercised to record serial QT/JT intervals
      over 5 min periods in IC mode and then in VP mode. Six different QT correction
      methods for heart rate were applied to assess the effect (i) of pacing mode (IC
      vs. VP) and (ii) of heart rate on the derived QT(c)/JT(c) intervals by mixed
      effects linear models. Following VP, the uncorrected QT/JT intervals as well as
      the JTc intervals shortened (P < 0.001), whereas the QTc intervals prolonged (P <
      0.001). In both patient groups, the Framingham and Nomogram methods demonstrated
      the optimal balance to assess QTc, with low heart rate dependence during VP and
      minimal interaction between pacing mode and heart rate. The Rautaharju formula
      provided excellent correction for the QT changes induced by VP, but the QTc
      interval responded differently to rate changes in IC vs. VP mode. Bazett's
      formula exaggerated QTc/JTc rate dependency during VP. CONCLUSION: The Framingham
      and Nomogram correction methods perform most reliably in assessing the underlying
      QT interval during IC from the ventricular paced QT interval.

PMID- 23118008
TI  - Prior aspirin therapy and cardiovascular implantable electronic device
      infections.

PMID- 23118007
TI  - Standard 12-lead electrocardiography measures predictive of increased appropriate
      therapy in implantable cardioverter defibrillator recipients.
AB  - AIMS: Identification of patients most likely to benefit from implantable
      cardioverter defibrillator (ICD) implant remains a complex challenge. This study
      aimed to investigate the utility of measures derived from standard 10 s 12-lead
      electrocardiogrphy (ECG) without complex signal processing in predicting
      appropriate therapy in an ICD population. METHODS AND RESULTS: We examined 108
      ICD patients for primary (n = 32) and secondary prevention (n = 76). Baseline
      clinical data and characteristics of QRS complex, T-wave, and heart rate from
      standard 12-lead ECG were examined and related to the occurrence of subsequent
      appropriate therapy. Over a mean follow-up of 29 +/- 11 months, 44% of patients
      received appropriate therapy. Patients with depressed heart rate variability
      (HRV) (<=6.5%) were 2.68 [95% confidence interval (CI) 1.21-5.90, P = 0.015]
      times more likely to receive appropriate therapy than patients with HRV >6.5%. In
      patients with bundle branch block (BBB), large QRS dispersion of >39 ms was
      associated with 2.88 times risk (95% CI 1.24-6.71, P = 0.014) of experiencing
      appropriate therapy than those with QRS dispersion <39 ms. In patients without
      BBB, reduced maximum T-wave amplitude (<0.4 mV) were 3.82 times (95% CI 1.63
      8.93, P = 0.002) more likely to receive appropriate therapy compared with those
      with maximum T-wave amplitude >0.4 mV. History of atrial arrhythmia [hazard ratio
      (HR) = 2.30, 95% CI 1.29-4.12, P = 0.005] and secondary prevention (HR = 2.55,
      95% CI 1.14-5.71, P = 0.022) were also predictive of device therapy. CONCLUSION:
      Measurements from standard 12-lead ECG were predictive of appropriate therapy in
      a heterogeneous ICD population. Incorporation of 12-lead ECG parameters such as
      these into risk stratification models may improve our ability to select patients
      for ICD implantation.

PMID- 23118009
TI  - Electric-field screening in atomically thin layers of MoS2: the role of
      interlayer coupling.

PMID- 23118010
TI  - Para-aminosalicylic acid acts as an alternative substrate of folate metabolism in
      Mycobacterium tuberculosis.
AB  - Folate biosynthesis is an established anti-infective target, and the antifolate
      para-aminosalicylic acid (PAS) was one of the first anti-infectives introduced
      into clinical practice on the basis of target-based drug discovery. Fifty years
      later, PAS continues to be used to treat tuberculosis. PAS is assumed to inhibit
      dihydropteroate synthase (DHPS) in Mycobacterium tuberculosis by mimicking the
      substrate p-aminobenzoate (PABA). However, we found that sulfonamide inhibitors
      of DHPS inhibited growth of M. tuberculosis only weakly because of their
      intracellular metabolism. In contrast, PAS served as a replacement substrate for
      DHPS. Products of PAS metabolism at this and subsequent steps in folate
      metabolism inhibited those enzymes, competing with their substrates. PAS is thus
      a prodrug that blocks growth of M. tuberculosis when its active forms are
      generated by enzymes in the pathway they poison.

PMID- 23118011
TI  - Mice lacking a Myc enhancer that includes human SNP rs6983267 are resistant to
      intestinal tumors.
AB  - Multiple cancer-associated single-nucleotide polymorphisms (SNPs) have been
      mapped to conserved sequences within a 500-kilobase region upstream of the MYC
      oncogene on human chromosome 8q24. These SNPs may affect cancer development
      through altered regulation of MYC expression, but this hypothesis has been
      difficult to confirm. We generated mice deficient in Myc-335, a putative MYC
      regulatory element that contains rs6983267, a SNP accounting for more human
      cancer-related morbidity than any other genetic variant or mutation. In Myc-335
      null mice, Myc transcripts were expressed in the intestinal crypts in a pattern
      similar to that in wild-type mice but at modestly reduced levels. The mutant mice
      displayed no overt phenotype but were markedly resistant to intestinal
      tumorigenesis induced by the APCmin mutation. These results establish that a
      cancer-associated SNP identified in human genome-wide association studies has a
      functional effect in vivo.

PMID- 23118012
TI  - Influence of threonine metabolism on S-adenosylmethionine and histone
      methylation.
AB  - Threonine is the only amino acid critically required for the pluripotency of
      mouse embryonic stem cells (mESCs), but the detailed mechanism remains unclear.
      We found that threonine and S-adenosylmethionine (SAM) metabolism are coupled in
      pluripotent stem cells, resulting in regulation of histone methylation. Isotope
      labeling of mESCs revealed that threonine provides a substantial fraction of both
      the cellular glycine and the acetyl-coenzyme A (CoA) needed for SAM synthesis.
      Depletion of threonine from the culture medium or threonine dehydrogenase (Tdh)
      from mESCs decreased accumulation of SAM and decreased trimethylation of histone
      H3 lysine 4 (H3K4me3), leading to slowed growth and increased differentiation.
      Thus, abundance of SAM appears to influence H3K4me3, providing a possible
      mechanism by which modulation of a metabolic pathway might influence stem cell
      fate.

PMID- 23118013
TI  - The imprint of the extragalactic background light in the gamma-ray spectra of
      blazars.
AB  - The light emitted by stars and accreting compact objects through the history of
      the universe is encoded in the intensity of the extragalactic background light
      (EBL). Knowledge of the EBL is important to understand the nature of star
      formation and galaxy evolution, but direct measurements of the EBL are limited by
      galactic and other foreground emissions. Here, we report an absorption feature
      seen in the combined spectra of a sample of gamma-ray blazars out to a redshift
      of z ~ 1.6. This feature is caused by attenuation of gamma rays by the EBL at
      optical to ultraviolet frequencies and allowed us to measure the EBL flux density
      in this frequency band.

PMID- 23118014
TI  - Content-specific fronto-parietal synchronization during visual working memory.
AB  - Lateral prefrontal and posterior parietal cortical areas exhibit task-dependent
      activation during working memory tasks in humans and monkeys. Neurons in these
      regions become synchronized during attention-demanding tasks, but the
      contribution of these interactions to working memory is largely unknown. Using
      simultaneous recordings of neural activity from multiple areas in both regions,
      we find widespread, task-dependent, and content-specific synchronization of
      activity across the fronto-parietal network during visual working memory. The
      patterns of synchronization are prevalent among stimulus-selective neurons and
      are governed by influences arising in parietal cortex. These results indicate
      that short-term memories are represented by large-scale patterns of synchronized
      activity across the fronto-parietal network.

PMID- 23118016
TI  - High-resolution positron emission tomography/computed tomography imaging of the
      mouse heart.
AB  - Different animal models have been used to reproduce coronary heart disease, but
      in recent years mice have become the animals of choice, because of their short
      life cycle and the possibility of genetic manipulation. Various techniques are
      currently used for cardiovascular imaging in mice, including high-resolution
      ultrasound, X-ray computed tomography (CT), magnetic resonance imaging and
      nuclear medicine procedures. In particular, molecular imaging with cardiac
      positron emission tomography (PET) allows non-invasive evaluation of changes in
      myocardial perfusion, metabolism, apoptosis, inflammation and gene expression or
      measurement of changes in left ventricular functional parameters. With
      technological advances, dedicated small laboratory PET/CT imaging has emerged in
      cardiovascular research, providing in vivo a non-invasive, serial and
      quantitative assessment of left ventricular function, myocardial perfusion and
      metabolism at a molecular level. This non-invasive methodology might be useful in
      longitudinal studies to monitor cardiac biochemical parameters and might
      facilitate studies to assess the effect of different interventions after acute
      myocardial ischaemia.

PMID- 23118015
TI  - Disruption of functional organization within the primary motor cortex in children
      with autism.
AB  - Accumulating evidence suggests that motor impairments are prevalent in autism
      spectrum disorder (ASD), relate to the social and communicative deficits at the
      core of the diagnosis and may reflect abnormal connectivity within brain networks
      underlying motor control and learning. Parcellation of resting-state functional
      connectivity data using spectral clustering approaches has been shown to be an
      effective means of visualizing functional organization within the brain but has
      most commonly been applied to explorations of normal brain function. This article
      presents a parcellation of a key area of the motor network, the primary motor
      cortex (M1), a key area of the motor control network, in adults, typically
      developing (TD) children and children with ASD and introduces methods for
      selecting the number of parcels, matching parcels across groups and testing group
      differences. The parcellation is based solely on patterns of connectivity between
      individual M1 voxels and all voxels outside of M1, and within all groups, a gross
      dorsomedial to ventrolateral organization emerged within M1 which was left-right
      symmetric. Although this gross organizational scheme was present in both groups
      of children, statistically significant group differences in the size and
      segregation of M1 parcels within regions of the motor homunculus corresponding to
      the upper and lower limbs were observed. Qualitative comparison of the M1
      parcellation for children with ASD with that of younger and older TD children
      suggests that these organizational differences, with a lack of differentiation
      between lower limb/trunk regions and upper limb/hand regions, may be due, at
      least in part, to a delay in functional specialization within the motor cortex.

PMID- 23118017
TI  - High-resolution echocardiography in the assessment of cardiac physiology and
      disease in preclinical models.
AB  - The high temporal and spatial resolution of echocardiography makes it a powerful
      and reliable tool for the non-invasive study of cardiac phenotype and disease in
      both adult and embryonic preclinical models. This overview of the use of high
      resolution ultrasound for echocardiography highlights the present and potential
      applications of the technique.

PMID- 23118018
TI  - Role of 5-hydroxytryptamine 1B (5-HT1B) receptors in the regulation of ethanol
      intake in rodents.
AB  - Evidence indicates that the serotonergic system is important in mediating
      dependence on and craving for alcohol. Among serotonin receptors, 5
      hydroxytryptamine 1B (5-HT1B) receptors have been associated with drug abuse
      including alcohol. In this review, the neurocircuitry involving 5-HT1B receptors
      in central reward brain regions related to alcohol intake are discussed in
      detail. Emphasis has been placed on the pharmacological manipulations of 5-HT1B
      receptor-mediated alcohol intake. Furthermore, 5-HT1B auto- and hetero-receptors
      regulate alcohol intake through the regulatory mechanism involving release of 5
      HT, gamma-aminobutyric acid (GABA), dopamine, and glutamate is evaluated. Thus,
      interactions between 5-HT1B receptors and these neurotransmitter systems are
      suggested to modulate alcohol-drinking behavior. This review on the role of 5
      HT1B receptors in neurotransmitter release and consequent alcohol intake provides
      important information about the potential therapeutic role of 5-HT1B receptors
      for the treatment of alcohol dependence.

PMID- 23118019
TI  - In vivo and in vitro characterization of naltrindole-derived ligands at the kappa
      opioid receptor.
AB  - Accumulating evidence supports a role for kappa-opioid receptor antagonists in
      the treatment of mood disorders. Standard kappa-antagonists have an unusual
      pharmacodynamic action, with a single injection blocking receptor signaling for
      several weeks. Here, we have characterized the kappa-selective properties of two
      ligands, 5'-(2-aminomethyl) naltrindole (5'-AMN) and N-((Naltrindol-5-yl) methyl)
      pentanimidamide (5'-MABN), to identify whether modifications of the naltrindole
      side chain produces short-acting kappa-antagonists. Opioid receptor binding
      affinity and activity were assessed using [(3)H]-diprenorphine binding, guanosine
      5'-O-(3-[35S]-thio) triphosphate ([(35)S]-GTPgammaS) binding and isolated guinea
      pig ileum. Pharmacodynamic profiles of 5'-AMN and 5'-MABN (1-10 mg/kg) were
      investigated using the tail-withdrawal assay and diuresis. Efficacy was also
      determined in depression- and anxiety-related behavioral paradigms in CD-1 mice.
      Both 5'-AMN and 5'-MABN had high affinity for kappa-receptors (K (i) 1.36 +/-
      0.98 and 0.27 +/- 0.08, respectively) and were revealed as potent kappa
      antagonists (pA(2) 7.43 and 8.18, respectively) and MU-receptor antagonists
      (pA(2) 7.62 and 7.85, respectively) in the ileum. Contrary to our hypothesis, in
      vivo, 5'-AMN and 5'-MABN displayed long-lasting antagonist effects in mice,
      reducing the antinociceptive actions of U50,488 (10 mg/kg) at 28 and 21 days post
      injection, respectively. Interestingly, while 5'-AMN and 5'-MABN were not kappa
      selective, both compounds did show significant antidepressant- and anxiolytic
      like effects at 7-14 days post-injection in mice.

PMID- 23118020
TI  - DRD2/ANKK1 Taq1A (rs 1800497 C>T) genotypes are associated with susceptibility to
      second generation antipsychotic-induced akathisia.
AB  - Although the advent of atypical, second-generation antipsychotics (SGAs) has
      resulted in reduced likelihood of akathisia, this adverse effect remains a
      problem. It is known that extrapyramidal adverse effects are associated with
      increased drug occupancy of the dopamine 2 receptors (DRD2). The A1 allele of the
      DRD2/ANKK1, rs1800497, is associated with decreased striatal DRD2 density. The
      aim of this study was to identify whether the A1(T) allele of DRD2/ANKK1 was
      associated with akathisia (as measured by Barnes Akathisia Rating Scale) in a
      clinical sample of 234 patients who were treated with antipsychotic drugs.
      Definite akathisia (a score >= 2 in the global clinical assessment of akathisia)
      was significantly less common in subjects who were prescribed SGAs (16.8%) than
      those prescribed FGAs (47.6%), p < 0.0001. Overall, 24.1% of A1+ patients
      (A1A2/A1A1) who were treated with SGAs had akathisia, compared to 10.8% of A1-
      (thus, A2A2) patients. A1+ patients who were administered SGAs also had higher
      global clinical assessment of akathisia scores than the A1- subjects (p = 0.01).
      SGAs maintained their advantage over FGAs regarding akathisia, even in A1+
      patients who were treated with SGAs. These results strongly suggested that A1+
      variants of the DRD2/ANKK1 Taq1A allele do confer an associated risk for
      akathisia in patients who were treated with SGAs, and these variants may explain
      inconsistencies found across prior studies, when comparing FGAs and SGAs.

PMID- 23118021
TI  - A randomized, controlled pilot study of MDMA (+/- 3,4
      Methylenedioxymethamphetamine)-assisted psychotherapy for treatment of resistant,
      chronic Post-Traumatic Stress Disorder (PTSD).
AB  - Psychiatrists and psychotherapists in the US (1970s to 1985) and Switzerland
      (1988-1993) used MDMA legally as a prescription drug, to enhance the
      effectiveness of psychotherapy. Early reports suggest that it is useful in
      treating trauma-related disorders. Recently, the first completed pilot study of
      MDMA-assisted psychotherapy for PTSD yielded encouraging results. Designed to
      test the safety and efficacy of MDMA-assisted psychotherapy in patients with
      treatment-resistant PTSD; our randomized, double-blind, active-placebo controlled
      trial enrolled 12 patients for treatment with either low-dose (25 mg, plus 12.5
      mg supplemental dose) or full-dose MDMA (125 mg, plus 62.5 mg supplemental dose).
      MDMA was administered during three experimental sessions, interspersed with
      weekly non-drug-based psychotherapy sessions. Outcome measures used were the
      Clinician-Administered PTSD Scale (CAPS) and the Posttraumatic Diagnostic Scale
      (PDS). Patients were assessed at baseline, three weeks after the second and third
      MDMA session (end of treatment), and at the 2-month and 1-year follow-ups. We
      found that MDMA-assisted psychotherapy can be safely administered in a clinical
      setting. No drug-related serious adverse events occurred. We did not see
      statistically significant reductions in CAPS scores (p = 0.066), although there
      was clinically and statistically significant self-reported (PDS) improvement (p =
      0.014). CAPS scores improved further at the 1-year follow-up. In addition, three
      MDMA sessions were more effective than two (p = 0.016).

PMID- 23118022
TI  - Effects of antipsychotic treatment on cognition in healthy subjects.
AB  - Cognitive impairments can be observed in the majority of diseases with disturbed
      dopamine transmission. They are considered as core symptoms of schizophrenia, a
      disorder in which they appear to be particularly pronounced. Their
      neurobiological background is not yet sufficiently investigated, but dopaminergic
      systems are believed to play a crucial role. The aim of this single-blind,
      randomised, placebo-controlled study was to examine the effects of subchronic
      antidopaminergic treatment on cognitive functions in healthy subjects. In total,
      72 healthy volunteers, randomised into four groups, received one antidopaminergic
      substance (aripiprazole, haloperidol or reserpine) or placebo, respectively, for
      7 days. A comprehensive neurocognitive assessment was conducted at baseline, 24 h
      after the last medication intake and 7 days later. In the Digit Symbol
      Substitution Test a distinct, statistically significant improvement was measured
      in the second session in the placebo but not in the medication group. A
      significant group*time interaction for reaction times in three subtests of the
      Test battery for Attentional Performance (TAP) was also found. Our findings
      indicate that modulation of dopaminergic systems affects primarily speed of
      information processing, attention and learning. Absence of effects on other
      functions, differing from previous reports, may be an expression of a sufficient
      counter-regulation.

PMID- 23118023
TI  - A self-care retreat for pediatric hematology oncology nurses.
AB  - Pediatric hematology oncology nurses face a variety of stressors while working in
      this specialty field. Through hematology oncology staff group discussions, nurses
      identified a myriad physical and emotional stressors they experienced, and
      expressed concern regarding possible burnout. They described facing stressors
      related to experiencing loss, grief, moral and ethical dilemmas, and
      administering complex treatment regimens. To address these concerns, a hematology
      oncology nursing supportive care committee envisioned and implemented 3 off-site
      self-care retreats. The committee's primary purpose was to create a therapeutic
      and supportive environment for all participants, while allowing time for
      relaxation, reflection, and serenity. The primary goals for the retreats were to
      heal nurses from their reported past trauma and stress and to provide them
      effective coping strategies for the ongoing stressors they will inevitably face.
      In a collaborative effort, the committee members developed an agenda including
      presentations, group discussions, and relaxation activities. Written evaluations
      were completed by each participant to assess the benefit of the retreat. Overall
      feedback was extremely positive, with the majority of the participants finding
      great value in this experience.

PMID- 23118024
TI  - Arrested cell proliferation through cysteine protease activity of eukaryotic
      ribosomal protein S4.
AB  - S4 is an integral protein of the smaller subunit of cytosolic ribosome. In
      prokaryotes, it regulates the synthesis of ribosomal proteins by feedback
      inhibition of the alpha-operon gene expression, and it facilitates ribosomal RNA
      synthesis by direct binding to RNA polymerase. However, functional roles of S4 in
      eukaryotes are poorly understood, although its deficiency in humans is thought to
      produce Turner syndrome. We report here that wheat S4 is a cysteine protease
      capable of abrogating total protein synthesis in an actively translating cell
      free system of rabbit reticulocytes. The translation-blocked medium, imaged by
      atomic force microscopy, scanning electron microscopy, and transmission electron
      microscopy, shows dispersed polysomes, and the disbanded polyribosome elements
      aggregate to form larger bodies. We also show that human embryonic kidney cells
      transfected with recombinant wheat S4 are unable to grow and proliferate. The
      mutant S4 protein, where the putative active site residue Cys 41 is replaced by a
      phenylalanine, can neither suppress protein synthesis nor arrest cell
      proliferation, suggesting that the observed phenomenon arises from the cysteine
      protease attribute of S4. The results also inspire many questions concerning in
      vivo significance of extraribosomal roles of eukaryotic S4 performed through its
      protease activity.

PMID- 23118025
TI  - Primocolonization is associated with colonic epithelial maturation during
      conventionalization.
AB  - Interaction between the gut microbiota and the host starts immediately after
      birth with the progressive colonization of the sterile intestine. Our aim was to
      investigate the interactions taking place in the colonic epithelium after the
      first exposure to gut microbiota. Germ-free (GF) rats were inoculated with two
      different microbiotas: the first, obtained from suckling rats, was rich in
      primocolonizing bacteria and the second, obtained from adult rats, was
      representative of a mature microbiota. Once transferred into GF rats, these two
      microbiotas evolved such that they converged, and recapitulated the
      primocolonization pattern, mimicking the chronological scheme of implantation
      following birth. The two microbiotas induced common responses in the colonic
      epithelium: a transitory proliferative phase followed by a compensatory phase
      characterized by increases in the abundance of p21(Cip1) and p27(Kip1) and in the
      number of goblet cells. The effects of the two microbiotas diverged only through
      their effects on colonic transporters. Analyses of solute carriers and aquaporins
      revealed that functional maturation was more pronounced following exposure to
      adult microbiota than suckling microbiota. The colon matured in parallel with the
      evolution of the microbiota composition, and we therefore suggest a link between
      intestinal events regulating homeostasis of the colon and modulation of microbial
      composition.

PMID- 23118026
TI  - Phosphatase and tensin homolog regulates stability and activity of EphB1
      receptor.
AB  - Deregulation of receptor tyrosine kinases (RTKs) is linked to a broad range of
      cancers, stressing the necessity of studying their regulatory pathways. We and
      others demonstrated previously that c-Cbl is necessary for the lysosomal
      degradation of erythropoietin-producing hepatocellular B1 (EphB1) carcinoma and
      epidermal growth factor receptor (EGFR) RTKs. Moreover, the tumor suppressor
      phosphatase and tensin homolog (PTEN) was shown to modulate c-Cbl-dependent EGFR
      degradation. We therefore investigated the involvement of PTEN in EphB1 signaling
      and degradation. We used PTEN mutants, PTEN, and NHERF1 small interfering RNA in
      CHO-EphB1 and SW480 cells endogenously expressing EphB1 to delineate EphB1-PTEN
      interactions. PTEN was constitutively associated with c-Cbl, protecting it from
      degradation. EphB1 stimulation triggered ~50% serine-threonine PTEN
      dephosphorylation and PTEN-Cbl complex disruption, a process requiring PTEN
      protein phosphatase activity. Both proteins independently translocated to EphB1,
      with PTEN in association with the scaffold protein NHERF1. Biologically, PTEN
      lipid phosphatase activity impairs EphB1-dependent cell adhesion and chemotaxis.
      This study demonstrates for the first time in mammalian cells that the Eph
      receptor and PTEN associate and influence their signaling. Moreover, it
      contributes to the emerging concept that PTEN regulates expression of RTKs
      through modulation of their degradation. Finally, it reveals a new role for PTEN
      protein phosphatase activity involved in this process.

PMID- 23118027
TI  - The immunoglobulin domain of the sodium channel beta3 subunit contains a surface
      localized disulfide bond that is required for homophilic binding.
AB  - The beta subunits of voltage-gated sodium (Na(v)) channels possess an
      extracellular immunoglobulin (Ig) domain that is related to the L1 family of cell
      adhesion molecules (CAMs). Here we show that in HEK293 cells, secretion of the
      free Ig domain of the beta3 subunit is reduced significantly when it is
      coexpressed with the full-length beta3 and beta1 subunits but not with the beta2
      subunit. Using immunoprecipitation, we show that the beta3 subunit can mediate
      trans homophilic-binding via its Ig domain and that the beta3-Ig domain can
      associate heterophilically with the beta1 subunit. Evolutionary tracing analysis
      and structural modeling identified a cluster of surface-localized amino acids
      fully conserved between the Ig domains of all known beta3 and beta1 sequences. A
      notable feature of this conserved surface cluster is the presence of two adjacent
      cysteine residues that previously we have suggested may form a disulfide bond. We
      now confirm the presence of the disulfide bond in beta3 using mass spectrometry,
      and we show that its integrity is essential for the association of the full
      length, membrane-anchored beta3 subunit with itself. However, selective reduction
      of this surface disulfide bond did not inhibit homophilic binding of the purified
      beta3-Ig domain in free solution. Hence, the disulfide bond itself is unlikely to
      be part of the homophilic binding site. Rather, we suggest that its integrity
      ensures the Ig domain of the membrane-tethered beta3 subunit adopts the correct
      orientation for productive association to occur in vivo.

PMID- 23118028
TI  - Adaptive radiation-induced epigenetic alterations mitigated by antioxidants.
AB  - Humans are exposed to low-dose ionizing radiation (LDIR) from a number of
      environmental and medical sources. In addition to inducing genetic mutations,
      there is concern that LDIR may also alter the epigenome. Such heritable effects
      early in life can either be positively adaptive or result in the enhanced
      formation of diseases, including cancer, diabetes, and obesity. Herein, we show
      that LDIR significantly increased DNA methylation at the viable yellow agouti
      (A(vy)) locus in a sex-specific manner (P=0.004). Average DNA methylation was
      significantly increased in male offspring exposed to doses between 0.7 and 7.6
      cGy, with maximum effects at 1.4 and 3.0 cGy (P<0.01). Offspring coat color was
      concomitantly shifted toward pseudoagouti (P<0.01). Maternal dietary antioxidant
      supplementation mitigated both the DNA methylation changes and coat color shift
      in the irradiated offspring. Thus, LDIR exposure during gestation elicits
      epigenetic alterations that lead to positive adaptive phenotypic changes that are
      negated with antioxidants, indicating they are mediated in part by oxidative
      stress. These findings provide evidence that in the isogenic A(vy) mouse model,
      epigenetic alterations resulting from LDIR play a role in radiation hormesis,
      bringing into question the assumption that every dose of radiation is harmful.

PMID- 23118029
TI  - C5aR and C3aR antagonists each inhibit diet-induced obesity, metabolic
      dysfunction, and adipocyte and macrophage signaling.
AB  - Mammalian survival depends on metabolizing nutrients, storing energy, and
      combating infection. Complement activation in blood triggers energy-depleting
      immune responses to fight infections. Here we identify surprising energy
      conserving roles for complement proteins C5a and C3a and their receptors, C5aR
      and C3aR, roles that are contraindicated in complement biology. Rats fed a high
      carbohydrate high-fat diet developed obesity, visceral adiposity, adipose
      inflammation, glucose/insulin intolerance, and cardiovascular dysfunction that
      correlated with increased plasma C3a, adipose C5aR, and C3aR. These in vivo
      changes were dramatically attenuated by receptor-selective antagonists of either
      C5aR (5 mg/kg/d p.o.) or C3aR (30 mg/kg/d p.o.), which both reduced
      proinflammatory adipokines and altered expression of inflammatory genes in
      adipose tissue. In vitro C5a and C3a (100 nM) exhibited novel insulin-like
      effects on 3T3-L1 adipocytes, promoting energy conservation by increasing glucose
      and fatty acid uptake while inhibiting cAMP signaling and lipolysis, and induced
      PGE(2) release from macrophages, effects all blocked by each respective
      antagonist (10 MUM). These studies reveal important new links between complement
      signaling and metabolism, highlight new complement functions on adipocytes and in
      adipose tissue, demonstrate how aberrant immune responses may exacerbate obesity
      and metabolic dysfunction, and show that targeting C3aR or C5aR with antagonists
      is a new strategy for treating metabolic dysfunction.

PMID- 23118030
TI  - Mathematical models as an aid for improving the validity of descriptive
      psychiatry.
AB  - Despite available therapies, mental disorders are the predominant chronic
      diseases of young people. Increasing the validity of descriptive psychiatry is
      now essential. Mathematical approaches can help characterise clinical phenotypes
      and aid both causal research and therapeutics in the community and the clinic.

PMID- 23118031
TI  - Depression and cardiovascular disease: the end of simple models.
AB  - In this editorial, we propose that the association between depression and
      cardiovascular disease may be conceptualised as a continuous, bidirectional
      process that originates in youth. The paper byAberg and colleagues in this issue
      adds to this literature showing that low cardiovascular fitness at adolescence
      increases the risk of future depression.

PMID- 23118032
TI  - Preventive strategies in depression: gathering evidence for risk factors and
      potential interventions.
AB  - This editorial critiques the recent literature concerning both vitamin D
      deficiency in major depression and supplementation as a treatment strategy, and
      contextualises it within a broader approach to the prevention of depression,
      based on the recent evidence for lifestyle as a risk factor for depression and
      anxiety.

PMID- 23118033
TI  - The new generation of psychosocial interventions for dementia care.
AB  - The new generation of psychosocial interventions for dementia has been
      characterised by great improvements in methodology and high-quality randomised
      controlled trials, including cost-effectiveness analyses. There are a growing
      number of interventions with established effectiveness but despite this there can
      be difficulties with implementation in practice.

PMID- 23118034
TI  - Improving quality of life for people with dementia in care homes: making
      psychosocial interventions work.
AB  - BACKGROUND: Psychosocial interventions can improve behaviour and mood in people
      with dementia, but it is unclear how to maximise their effectiveness or
      acceptability in residential settings. AIMS: To understand what underlies the
      successful implementation of psychosocial interventions in care homes. METHOD:
      Systematic review and meta-synthesis of qualitative research. RESULTS: The
      synthesis of 39 qualitative papers revealed that beneficial psychosocial
      interventions met the needs of people with dementia to connect with others, make
      a meaningful contribution and reminisce. Successful implementation rested on the
      active engagement of staff and family and the continuing provision of tailored
      interventions and support. This necessitated staff time, and raised issues around
      priorities and risk, but ultimately helped redefine staff attitudes towards
      residents and the caregiving role. CONCLUSIONS: The findings from the meta
      synthesis can help to inform the development and evaluation of psychosocial
      interventions in care homes and support their widespread implementation in
      clinical settings.

PMID- 23118035
TI  - High-risk strategies v. universal precautions against suicide.

PMID- 23118036
TI  - Child conduct problems and social skills in a middle-income country.

PMID- 23118037
TI  - Assessing the role of cerebrovascular disease in the incidence of geriatric
      depression.

PMID- 23118038
TI  - Aliskiren, at low doses, reduces the electrical remodeling in the heart of the
      TGR(mRen2)27 rat independently of blood pressure.
AB  - METHODS: The influence of chronic administration of low doses of aliskiren (5
      mg/kg/day, i.p.) for a period of eight weeks on cardiac electrophysiological and
      structural remodeling was investigated in transgenic (TGR)(mRen-2)27 rats.
      Cardiac and plasma angiotensin II (Ang II) levels were determined by ELISA before
      and after administration of the drug. Moreover, histological,
      electrophysiological and echocardiographic studies were performed in controls and
      at the end of eight weeks of aliskiren administration. RESULTS: 1) The cardiac
      Ang II levels were significantly reduced while the plasma Ang II levels were not
      significantly decreased in rats treated with low doses of aliskiren; 2)
      echocardographic studies showed a decrease of left ventricle diameter (LVD), left
      ventricle posterior wall thickness (LVPW), left ventricle end diastolic volume
      (LVEDV) and increased ejection fraction (EF); 3) aliskiren improved the impulse
      propagation, increased the cardiac refractoriness and reduced the incidence of
      triggered activity; 4) perivascular and interstitial fibrosis were greatly
      reduced, which explains the increase in conduction velocity. All these effects of
      aliskiren were found independently of blood pressure, suggesting that the
      beneficial effect of aliskiren was related to an inhibition of the local cardiac
      renin angiotensin system; and 5) the effect of mechanical stretch on action
      potential duration, conduction velocity and spontaneous rhythmicity was changed
      by aliskiren, supporting the hypothesis presented here that the beneficial effect
      of the drug on cardiac remodeling is related to a decreased sensitivity of
      cardiac muscle to mechanical stress.

PMID- 23118039
TI  - Screening for primary aldosteronism in a primary care unit.
AB  - OBJECTIVE: Primary aldosteronism (PA) is a common cause of secondary hypertension
      but the reported prevalence varies. Few studies have been carried out in primary
      care. We investigated the prevalence of PA by screening with the aldosterone to
      renin ratio (ARR). DESIGN AND METHODS: Patients with hypertension were recruited
      from a primary care unit and investigated in a university hospital setting. Of
      235 patients asked to participate 77% accepted. Antihypertensive medication apart
      from amiloride and spironolactone was maintained. The cut-off level for a
      positive ARR was lower than in clinical practice (> 50 pmol/ng with aldosterone >
      350 pmol/l) to adjust for any suppressive effects of medication. A positive ARR
      was followed by a confirmatory evaluation. RESULTS: The frequency of confirmed PA
      was 1.6% and including cases with a positive ARR who refused further
      investigation it would be 3.3% at most. In primary hypertension angiotensin
      receptor blockers, angiotensin-converting enzyme inhibitors and thiazide
      diuretics markedly suppressed the ARR by increasing renin levels. CONCLUSION: The
      detection rate of PA in our study is in the lower part of the wide range shown in
      previous studies. Larger population studies are needed to establish the true
      prevalence in primary care. Future studies may clarify if the present cut-off
      levels allow detection of very mild PA.

PMID- 23118040
TI  - Views of professionalism: a veterinary institutional perspective.
AB  - In many western countries, there has been a marked change in the demographic
      profile of those entering the veterinary profession, with a shift from a
      predominantly male to a predominantly female intake. There have been parallel
      changes in society, with greater emphasis on human rights and work-life balance.
      It is, therefore, timely to consider what constitutes correct professional
      conduct for the profession, as there is the potential for problems to arise over
      the interpretation of 'professionalism' due to cultural and generational
      differences. A cross-section of staff and students within one veterinary
      institution were invited to take part in a survey exploring their prioritisation
      of 10 aspects of the professional role. A cluster analysis was performed, and
      four distinctly different profiles were established according to the views held
      by the cluster members. Cluster membership was found to significantly correlate
      to career stage, with altruism and social justice progressively giving way to
      professional autonomy and dominance. All four clusters in this educational
      environment prioritised technical and interpersonal competences above all other
      aspects of the professional role.

PMID- 23118041
TI  - Epidemiological investigation of selected pigeon viral infections in Poland.
AB  - Due to a lack of data in regard to the spread of viral infections in Polish
      pigeon populations, studies were undertaken to assess the frequency of adeno-,
      circo- and herpesvirus infections in flocks of pigeons across the entire country.
      In total, 107 flocks were examined, of which 61 per cent consisted of racing and
      39 per cent of fancy pigeons. The flocks were divided into groups according to
      breed (racing and fancy pigeons) as well as physical condition (healthy and
      sick). In the studied pigeon flocks, the pigeon circovirus (PiCV) genetic
      material was the most frequently detected (44.5-100 per cent depending on the
      group), pigeon herpesvirus genetic material was second in frequency (0-30 per
      cent depending on the group), while genetic material of pigeon adenovirus was
      found only in two flocks of young birds with clinical symptoms of Young Pigeon
      Disease Syndrome (YPDS). The presence of fowl adenovirus (FAdV) genetic material
      was not detected in any of the studied flocks. Results obtained demonstrate a
      wide spread of circovirus in pigeon flocks in Poland, and substantiate earlier
      theories proposed by other authors, that immunosuppression evoked by PiCV
      infection is one of the main causative agents of YPDS.

PMID- 23118042
TI  - Fluoroscopic evaluation of gastrointestinal transit time in African Grey parrots.

PMID- 23118043
TI  - Guttural pouch mycosis in horses: a retrospective study of 28 cases.
AB  - The medical records of 28 horses with guttural pouch mycosis were reviewed. The
      most commonly observed clinical signs were nasal discharge, epistaxis, dysphagia
      and/or cough. All 28 horses had the disease unilaterally, however, in five of
      them, it had spread into the contralateral pouch via the mesial septum. Three
      horses were treated medically, 11 horses underwent surgery and seven horses were
      treated both medically and surgically. Fifty percent of horses (14/28) were
      euthanased or died, fifty percent of horses (14/28) survived. There was no
      significant correlation between treatment method (medical, surgical, combination)
      and survival rate. The most common reason for euthanasia was dysphagia due to
      pharyngeal dysfunction. There was a highly significant correlation between the
      presence of dysphagia and non-survival (p=0.008).

PMID- 23118044
TI  - A predictive model for reproductive performance following abortion in
      Thoroughbred mares.
AB  - Pregnancy losses include early embryonic death (EED) and later (postimplantation)
      abortion. Abortions, particularly Equid herpesvirus (EHV-1) abortion epizootics,
      cause severe economic and production losses. The long-term effects of EHV-1 and
      other abortions on subsequent reproductive performance in broodmare populations,
      however, remain undefined. This study described the relationships of EED and
      abortion with the following reproductive outcomes in Thoroughbred systems:
      breeding efficiency, month of last breeding, subsequent pregnancy and live foal
      rates. A prospective cohort study in broodmare populations following EHV-1
      epizootics on two South African farms was used to develop predictive models of
      the relative influences and interactions of reproductive variables associated
      with EHV-1 and other abortion causes on reproductive performance. EED predicted
      all the reproductive outcomes. Abortion predicted increased effort and month of
      breeding to establish pregnancy, but not becoming pregnant or foaling. Increasing
      age predicted decreased reproductive efficiency, and pregnancy and foaling
      probabilities. Mare reproductive status predicted breeding efficiency and the
      last month of breeding, but not establishing pregnancy. The last month of
      breeding predicted efficiency, pregnancy and foaling. Interestingly, breeding in
      the first month of the season was associated with an improved probability of
      pregnancy among barren mares.

PMID- 23118045
TI  - Measurement of the radioactivity in the excreta of cats treated with iodine-131
      for hyperthyroidism.
AB  - When hyperthyroidism is treated with radioiodine, up to 75 per cent of the
      injected dose is excreted in the faeces and urine, which poses hazards to
      handlers. Three groups of hyperthyroid cats were treated with 120, 150 and 200
      megabecquerel (MBq) of radioiodine, and samples of faeces and urine-soaked litter
      (USL) were collected over a 24-hour period, once a week, for four weeks. The
      amount of radioactivity in each homogenised sample was then measured using a
      sodium iodide detector. Radioactivity significantly decreased in both the faecal
      and USL samples over the first three weeks. Regardless of dose, there was no
      significant difference in faecal and USL samples between weeks 3 and 4. Faecal
      radioactivity was generally higher than the USL, but both were variable between
      cats at each time point. There were some significant differences in radioactivity
      between doses at various time points, but these were very small compared with the
      differences between time points. From the results, the maximum likely exposure to
      a worker or owner handling the waste was calculated. For cats treated with up to
      200 MBq, radioactivity levels after two weeks were such that the waste could be
      designated as 'very low level waste' (a UK statutory definition) for disposal
      purposes.

PMID- 23118046
TI  - Effects of levamisole and ranitidine on antibody-forming responses induced by
      killed Mycoplasma vaccine antigens in Saanen goats.

PMID- 23118047
TI  - Epidemiological survey of the hoof wall cavity ('Gidoh' in Japanese) in
      racehorses.
AB  - In October 2001, a survey was conducted about cavities formed within the hoof
      wall (called GIDOH in Japanese) of racehorses at the Ritto and Miho Training
      Centres, which are managed by the Japan Racing Association (JRA). Gidoh is
      defined as a progressive cavity within the deep layers between the stratum medium
      and stratum internum. A total of 148 out of 5386 surveyed horses (2.75 per cent)
      were affected. Out of 244 affected feet, fore hooves (84.02 per cent) were more
      susceptible than hind hooves, and the site most affected was midline dead centre
      of the toe (59.62 per cent) which tends to place extra stress at the break-over
      point in a straight-line exercise. Logistic regression analysis revealed that
      prevalence was significantly related with horse affiliation (OR 0.65, 95 per cent
      CI 0.46 to 0.91) and age (OR 1.43 per one year, 95 per cent CI 1.27 to 1.61). We
      hypothesised that the primary cause of Gidoh development in JRA stables was
      mechanical deformation of the hoof wall during exercise, and secondary exciting
      causes can subsequently lead to the spread of the lesion over the entire hoof
      wall.

PMID- 23118049
TI  - Association of breeding conditions with prevalence of osteochondrosis in foals.
AB  - Osteochondrosis (OC) is the most common developmental orthopaedic disease in
      horses and represents a major problem to the horse industry. The complete
      mechanism of this multifactorial disease is not yet elucidated, but it is
      accepted that OC lesions are the result of intrinsic genetic and external
      factors. The aim of the present work was to evaluate the relationship between
      breeding management and OC. Breeding conditions were recorded, and a radiological
      examination was performed in 223 foals. Feeding practice and housing management
      were analysed in a multivariate model to determine risk factors for OC in three
      periods: gestation, birth to weaning and weaning to one-year-old. The major
      breakthrough of this study is the significant relationship between OC development
      and (1) the maternal nutrition during gestation and (2) the type of housing of
      the foals during their first year. It appears that mares fed with concentrates
      during gestation are more likely to produce foals that are subsequently affected
      by OC compared with other mares (P<0.05). Foals housed exclusively at pasture
      until one year of age are significantly less affected than foals exclusively
      housed in box or, alternatively, in box and at pasture (P<0.05). These results
      underline the role of the energy metabolism and the level of exercise in the
      aetiologic process of the disease, and help to develop preventive strategies
      during the crucial period of gestation to one year of age of the foal.

PMID- 23118050
TI  - QX-like infectious bronchitis virus isolated from cases of proventriculitis in
      commercial broilers in England.

PMID- 23118051
TI  - Pelvic differences between brachycephalic and mesaticephalic cats and indirect
      pelvimetry assessment.
AB  - Pelvic measurements were carried out in cats with various cranial conformations
      to (1) determine pelvic morphometry, (2) compare any pelvic differences with
      cranial conformation and gender and (3) determine whether body biometrics can be
      used to predict pelvic measurements. Thirteen brachycephalic and 14
      mesaticephalic female cats and 17 brachycephalic and nine mesaticephalic male
      cats were used. Body and external pelvic measurements, as well as pelvic
      radiographs, were performed. Brachycephalic females all had external pelvic and
      radiographic measurements that were significantly smaller than those of the
      mesaticephalic females, including smaller pelvic inlet and outlet areas and a
      smaller pelvic canal shape. Brachycephalic females had wider and flatter heads
      than do mesaticephalic females. Similarly, brachycephalic males all have
      radiographic pelvic measurements that are smaller than those of mesaticephalic
      males. Males had larger pelvis measurements than did their female counterparts
      for both cranial types, and indirect pelvimetry did not demonstrate good
      predictive value in determining the internal pelvic measurements. Thus, we
      conclude that pelvic differences exist between genders and between brachycephalic
      and mesaticephalic cats. Furthermore, body biometric measurements do not have
      good predictive value for determining internal pelvic measurements.

PMID- 23118052
TI  - Effects of ovariohysterectomy on intra-abdominal pressure and abdominal perfusion
      pressure in cats.
AB  - Intra-abdominal pressure (IAP) and abdominal perfusion pressure (APP) have shown
      clinical relevance in monitoring critically ill human beings submitted to
      abdominal surgery. Only a few studies have been performed in veterinary medicine.
      The aim of this study was to assess how pregnancy and abdominal surgery may
      affect IAP and APP in healthy cats. For this purpose, pregnant (n=10) and non
      pregnant (n=11) queens undergoing elective spaying, and tomcats (n=20, used as
      controls) presented for neutering by scrotal orchidectomy were included in the
      study. IAP, mean arterial blood pressure (MAP), APP, heart rate and rectal
      temperature (RT) were determined before, immediately after, and four hours after
      surgery. IAP increased significantly immediately after abdominal surgery in both
      female groups when compared with baseline (P<0.05) and male (P<0.05) values, and
      returned to initial perioperative readings four hours after surgery. Tomcats and
      pregnant females (P<0.05) showed an increase in MAP and APP immediately after
      surgery decreasing back to initial perioperative values four hours later. A
      significant decrease in RT was appreciated immediately after laparotomy in both
      pregnant and non-pregnant queens. IAP was affected by abdominal surgery in this
      study, due likely to factors, such as postoperative pain and hypothermia.
      Pregnancy did not seem to affect IAP in this population of cats, possibly due to
      subjects being in early stages of pregnancy.

PMID- 23118053
TI  - An outbreak of tuberculosis in Lleyn sheep in the UK associated with clinical
      signs.
AB  - This case report describes an outbreak of Mycobacterium bovis infection a Lleyn
      sheep flock associated with clinical signs of illthrift. There was no known
      direct contact with tuberculous cattle although bovine tuberculosis (bTB) is
      endemic in the area. The spoligotype isolated from the diseased sheep was the
      local spoligotype. The repeated use of the comparative intradermal tuberculin
      test, and the subsequent removal of reactor animals, resulted in apparent
      elimination of bTB from the flock. Lesions caused by M bovis in sheep may contain
      very few acid-fast bacilli, and gross lesions may resemble those found in cases
      of Caseous Lymphadenitis. Routine meat inspection may, therefore, not always
      easily detect this notifiable disease.

PMID- 23118056
TI  - Increased hemoglobin mass and VO2max with 10 h nightly simulated altitude at 3000
      m.
AB  - PURPOSE: To quantify the changes of hemoglobin mass (Hbmass) and maximum oxygen
      consumption (VO2max) after 22 days training at 1300-1800 m combined with nightly
      exposure to 3000-m simulated altitude. We hypothesized that with simulated 3000-m
      altitude, an adequate beneficial dose could be as little as 10 h/24 h. METHODS:
      Fourteen male collegiate runners were equally divided into 2 groups: altitude
      (ALT) and control (CON). Both groups spent 22 days at 1300-1800 m. ALT spent 10
      h/night for 21 nights in simulated altitude (3000 m), and CON stayed at 1300 m.
      VO2max and Hbmass were measured twice before and once after the intervention.
      Blood was collected for assessment of percent reticulocytes (%retics), serum
      erythropoietin (EPO), ferritin, and soluble transferrin receptor (sTfR)
      concentrations. RESULTS: Compared with CON there was an almost certain increase
      in absolute VO2max (8.6%, 90% confidence interval 4.8-12.6%) and a likely
      increase in absolute Hbmass (3.5%; 0.9-6.2%) at postintervention. The %retics
      were at least very likely higher in ALT than in CON throughout the 21 nights, and
      sTfR was also very likely higher in the ALT group until day 17. EPO of ALT was
      likely higher than that of CON on days 1 and 5 at altitude, whereas serum
      ferritin was likely lower in ALT than CON for most of the intervention.
      CONCLUSIONS: Together the combination of the natural and simulated altitude was a
      sufficient total dose of hypoxia to increase both Hbmass and VO2max.

PMID- 23118055
TI  - Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors.
AB  - Small-molecule inhibitors of PARP are thought to mediate their antitumor effects
      as catalytic inhibitors that block repair of DNA single-strand breaks (SSB).
      However, the mechanism of action of PARP inhibitors with regard to their effects
      in cancer cells is not fully understood. In this study, we show that PARP
      inhibitors trap the PARP1 and PARP2 enzymes at damaged DNA. Trapped PARP-DNA
      complexes were more cytotoxic than unrepaired SSBs caused by PARP inactivation,
      arguing that PARP inhibitors act in part as poisons that trap PARP enzyme on DNA.
      Moreover, the potency in trapping PARP differed markedly among inhibitors with
      niraparib (MK-4827) > olaparib (AZD-2281) >> veliparib (ABT-888), a pattern not
      correlated with the catalytic inhibitory properties for each drug. We also
      analyzed repair pathways for PARP-DNA complexes using 30 genetically altered
      avian DT40 cell lines with preestablished deletions in specific DNA repair genes.
      This analysis revealed that, in addition to homologous recombination,
      postreplication repair, the Fanconi anemia pathway, polymerase beta, and FEN1 are
      critical for repairing trapped PARP-DNA complexes. In summary, our study provides
      a new mechanistic foundation for the rational application of PARP inhibitors in
      cancer therapy.

PMID- 23118061
TI  - Not different is not the same as the same: how can we tell?

PMID- 23118062
TI  - In search of a vasodilator: is ATP the answer?

PMID- 23118063
TI  - Airway epithelial cells: 'Bicarbonate in' ? 'Bicarbonate out'.

PMID- 23118064
TI  - Ageing, exercise and cardiovascular health: good and bad news.

PMID- 23118065
TI  - Maternal high fat diet programming of the endocrine system.

PMID- 23118066
TI  - Sodium loading and cutaneous microvascular function: more than skin deep.

PMID- 23118067
TI  - Blood flow-restricted resistance exercise: rapidly affecting the myofibre and the
      myonuclei.

PMID- 23118069
TI  - Definition of moderate ischemic mitral regurgitation: it's time to speak the same
      language.

PMID- 23118068
TI  - Rotation thromboelastography for the detection and characterization of
      lipoteichoid acid-induced activation of haemostasis in an in vitro sepsis model.
AB  - OBJECTIVES: In gram-positive sepsis, lipoteichoic acid (LTA) can induce
      alterations of haemostasis, potentially leading to disseminated intravascular
      coagulation. PATIENTS AND METHODS: Here, we demonstrate the effects of LTA on
      haemostasis in an in vitro model of gram-positive sepsis based on rotation
      thromboelastrography (ROTEM). RESULTS: In this model, LTA leads to time- and dose
      dependent shortening of the clotting time (CT), whereas other ROTEM parameters
      are unaffected. Following heat shock simulation, the LTA effect was blunted with
      equal CTs in the presence and in the absence of LTA. In addition, the shortening
      of CT by LTA was inhibited by addition of the protein synthesis inhibitor.
      CONCLUSION: Our work demonstrates that the ROTEM system is capable of detecting
      the LTA effect on haemostasis and provides a sensitive in vitro tool for research
      into the links between gram-positive sepsis and coagulation.

PMID- 23118070
TI  - Maximal aerobic power characteristics of male professional soccer players, 1989
      2012.
AB  - PURPOSE: The purpose of this investigation was to quantify maximal aerobic power
      (VO2max) in soccer as a function of performance level, position, age, and time of
      season. In addition, the authors examined the evolution of VO2max among
      professional players over a 23-y period. METHODS: 1545 male soccer players (22 +/
      4 y, 76 +/- 8 kg, 181 +/- 6 cm) were tested for VO2max at the Norwegian Olympic
      Training Center between 1989 and 2012. RESULTS: No differences in VO2max were
      observed among national-team players, 1st- and 2nd-division players, and juniors.
      Midfielders had higher VO2max than defenders, forwards, and goalkeepers (P <
      .05). Players <18 y of age had ~3% higher VO2max than 23- to 26-y-old players (P
      = .016). The players had 1.6% and 2.1% lower VO2max during off-season than
      preseason (P = .046) and in season (P = .021), respectively. Relative to body
      mass, VO2max among the professional players in this study has not improved over
      time. Professional players tested during 2006-2012 actually had 3.2% lower VO2max
      than those tested from 2000 to 2006 (P = .001). CONCLUSIONS: This study provides
      effect-magnitude estimates for the influence of performance level, player
      position, age, and season time on VO2max in men's elite soccer. The findings from
      a robust data set indicate that VO2max values ~62-64 mL . kg-1 . min-1 fulfill
      the demands for aerobic capacity in men's professional soccer and that VO2max is
      not a clearly distinguishing variable separating players of different standards.

PMID- 23118071
TI  - Alterations in peak ground-reaction force during 60-cm drop landings caused by a
      single session of repeated Wingate anaerobic tests.
AB  - CONTEXT: Lower extremity injury is prevalent among individuals participating in
      sports. Numerous variables have been reported as predisposing risk factors to
      injury; however, the effects of muscle fatigue on landing kinetics are unclear.
      OBJECTIVES: To investigate the effects of a single session of repeated muscle
      fatigue on peak vertical ground-reaction force (GRF) during drop landings.
      DESIGN: Mixed factorial with repeated measures. SETTING: Controlled laboratory.
      PARTICIPANTS: 10 female and 10 male healthy recreational athletes. INTERVENTION:
      Subjects performed 3 fatigued drop landings (60 cm) after four 20-s Wingate
      anaerobic tests (WATs) with 5 min of active recovery between fatigued conditions.
      MAIN OUTCOME MEASURES: Kinetic data of peak forefoot (F1) force, peak rear-foot
      (F2) force, and anteroposterior (AP) and mediolateral (ML) forces at both F1 and
      F2. RESULTS: A significant main effect was observed in the nonfatigued and
      fatigued drop landings in respect to peak F2 force. The greatest significant
      difference was shown between the first fatigued drop-landing condition and the
      last fatigued drop-landing condition. No significant difference was observed
      between genders for all GRF variables across fatigue conditions. CONCLUSION: A
      single session of repeated conditions of anaerobic muscle fatigue induced by WATs
      caused an initial reduction in peak F2 force followed by an increase in peak F2
      force across conditions. Muscle fatigue consequently alters landing kinetics,
      potentially increasing the risk of injury.

PMID- 23118072
TI  - Effects of a 4-week dynamic-balance-training program supplemented with Graston
      instrument-assisted soft-tissue mobilization for chronic ankle instability.
AB  - CONTEXT: A dynamic-balance-training (DBT) program supplemented with the Graston
      instrument-assisted soft-tissue mobilization (GISTM) technique has not been
      evaluated collectively as a treatment in subjects with chronic ankle instability
      (CAI). OBJECTIVE: To examine the effects of GISTM in conjunction with a DBT
      program on outcomes associated with CAI, including pain and disability, range of
      motion (ROM), and dynamic postural control. DESIGN: Pretest/posttest, repeated
      measures. SETTING: High school and a Division I mid-Atlantic university.
      PARTICIPANTS: Thirty-six healthy, physically active individuals (5 female, 31
      male; age 17.7 +/- 1.9 y; height 175.3 +/- 14.6 cm) with a history of CAI as
      determined by an ankle-instability questionnaire volunteered to be in this study.
      INTERVENTIONS: Subjects were randomly assigned to 1 of 3 intervention groups:
      both treatments (DBT/GISTM, n = 13), DBT and a sham GISTM treatment (DBT/GISTM-S,
      n = 12), or DBT and control-no GISTM (DBT/C, n = 11). All groups participated in
      a 4-wk DBT program consisting of low-impact and dynamic activities that was
      progressed from week to week. The DBT/GISTM and DBT/GISTM-S groups received the
      GISTM treatment or sham treatment twice a week for 8 min before performing the
      DBT program. Pretest and posttest measurements included the Foot and Ankle
      Ability Measure (FAAM), FAAM Sport, the visual analog scale (VAS), ankle ROM in 4
      directions, and the Star Excursion Balance Test (SEBT) in 3 directions. MAIN
      OUTCOME MEASURES: FAAM and FAAM-Sport scores, VAS, goniometric ROM (plantar
      flexion, dorsiflexion, inversion, eversion), and SEBT (anterior, posteromedial,
      posterolateral). RESULTS: Subjects in all groups posttest demonstrated an
      increase in FAAM, FAAM Sport, ROM, and SEBT in all directions but not in VAS,
      which decreased. No other results were significant. CONCLUSION: For subjects with
      CAI, dynamic postural control, ROM, pain and disability improved pretest to
      posttest regardless of group membership, with the largest effects found in most
      measures in the DBT/GISTM group.

PMID- 23118077
TI  - From cookstoves to oxygen concentrators: a few important tools can help tackle
      global respiratory disparities.

PMID- 23118078
TI  - Induced sputum biomarkers for monitoring cystic fibrosis lung disease.

PMID- 23118079
TI  - The fibrotic matrix in control: does the extracellular matrix drive progression
      of idiopathic pulmonary fibrosis?

PMID- 23118080
TI  - Genetic susceptibility to sarcoidosis, a chronic inflammatory disorder.

PMID- 23118081
TI  - Rhinovirus genetics and virulence: looking for needles in a haystack.

PMID- 23118082
TI  - Waiting in anticipation: the genetics of pulmonary arterial hypertension.

PMID- 23118083
TI  - Treatment of Mycobacterium abscessus: all macrolides are equal, but perhaps some
      are more equal than others.

PMID- 23118084
TI  - Making light of an interstitial process.

PMID- 23118085
TI  - Adenotonsillectomy outcomes in treatment of obstructive sleep apnea in children:
      a multicenter retrospective study.

PMID- 23118086
TI  - A 56-year-old man with an apparently normal oxygen saturation and a dead canary.

PMID- 23118087
TI  - Diagnosis of influenza in intensive care units: lower respiratory tract samples
      are better than nose-throat swabs.

PMID- 23118088
TI  - Cladribine is effective against cystic pulmonary Langerhans cell histiocytosis.

PMID- 23118089
TI  - Bronchial sleeve resection for a mucoepidermoid carcinoma, mimicking asthma in a
      27-year-old female.

PMID- 23118090
TI  - Safety 2012: Wellington shines!

PMID- 23118091
TI  - Living in the grey area: a case for data sharing in observational epidemiology.

PMID- 23118092
TI  - Polyphosphoinositide metabolism and Golgi complex morphology in hippocampal
      neurons in primary culture is altered by chronic ethanol exposure.
AB  - AIMS: Ethanol affects not only the cytoskeletal organization and activity, but
      also intracellular trafficking in neurons in the primary culture.
      Polyphosphoinositide (PPIn) are essential regulators of many important cell
      functions, including those mentioned, cytoskeleton integrity and intracellular
      vesicle trafficking. Since information about the effect of chronic ethanol
      exposure on PPIn metabolism in neurons is scarce, this study analysed the effect
      of this treatment on three of these phospholipids. METHODS: Phosphatidylinositol
      (PtdIns) levels as well as the activity and/or levels of enzymes involved in
      their metabolism were analysed in neurons chronically exposed to ethanol. The
      levels of phospholipases C and D, and phosphatidylethanol formation were also
      assessed. The consequence of the possible alterations in the levels of PtdIns on
      the Golgi complex (GC) was also analysed. RESULTS: We show that
      phosphatidylinositol (4,5)-bisphosphate and phosphatidylinositol (3,4,5)
      trisphosphate levels, both involved in the control of intracellular trafficking
      and cytoskeleton organization, decrease in ethanol-exposed hippocampal neurons.
      In contrast, several kinases that participate in the metabolism of these
      phospholipids, and the level and/or activity of phospholipases C and D, increase
      in cells after ethanol exposure. Ethanol also promotes phosphatidylethanol
      formation in neurons, which can result in the suppression of phosphatidic acid
      synthesis and, therefore, in PPIn biosynthesis. This treatment also lowers the
      phosphatidylinositol 4-phosphate levels, the main PPIn in the GC, with
      alterations in their morphology and in the levels of some of the proteins
      involved in structure maintenance. CONCLUSIONS: The deregulation of the
      metabolism of PtdIns may underlie the ethanol-induced alterations on different
      neuronal processes, including intracellular trafficking and cytoskeletal
      integrity.

PMID- 23118093
TI  - Combing signals from spontaneous reports and electronic health records for
      detection of adverse drug reactions.
AB  - OBJECTIVE: Data-mining algorithms that can produce accurate signals of
      potentially novel adverse drug reactions (ADRs) are a central component of
      pharmacovigilance. We propose a signal-detection strategy that combines the
      adverse event reporting system (AERS) of the Food and Drug Administration and
      electronic health records (EHRs) by requiring signaling in both sources. We claim
      that this approach leads to improved accuracy of signal detection when the goal
      is to produce a highly selective ranked set of candidate ADRs. MATERIALS AND
      METHODS: Our investigation was based on over 4 million AERS reports and
      information extracted from 1.2 million EHR narratives. Well-established
      methodologies were used to generate signals from each source. The study focused
      on ADRs related to three high-profile serious adverse reactions. A reference
      standard of over 600 established and plausible ADRs was created and used to
      evaluate the proposed approach against a comparator. RESULTS: The combined
      signaling system achieved a statistically significant large improvement over AERS
      (baseline) in the precision of top ranked signals. The average improvement ranged
      from 31% to almost threefold for different evaluation categories. Using this
      system, we identified a new association between the agent, rasburicase, and the
      adverse event, acute pancreatitis, which was supported by clinical review.
      CONCLUSIONS: The results provide promising initial evidence that combining AERS
      with EHRs via the framework of replicated signaling can improve the accuracy of
      signal detection for certain operating scenarios. The use of additional EHR data
      is required to further evaluate the capacity and limits of this system and to
      extend the generalizability of these results.

PMID- 23118094
TI  - Clinical audit of diabetes management can improve the quality of care in a
      resource-limited primary care setting.
AB  - OBJECTIVE: To determine whether clinical audit improved the performance of
      diabetic clinical processes in the health district in which it was implemented.
      DESIGN: Patient folders were systematically sampled annually for review. SETTING:
      Primary health-care facilities in the Metro health district of the Western Cape
      Province in South Africa. PARTICIPANTS: Health-care workers involved in diabetes
      management. INTERVENTION: Clinical audit and feedback. MAIN OUTCOME MEASURE: The
      Skillings-Mack test was applied to median values of pooled audit results for nine
      diabetic clinical processes to measure whether there were statistically
      significant differences between annual audits performed in 2005, 2007, 2008 and
      2009. Descriptive statistics were used to illustrate the order of values per
      process. RESULTS: A total of 40 community health centres participated in the
      baseline audit of 2005 that decreased to 30 in 2009. Except for two routine
      processes, baseline medians for six out of nine processes were below 50%. Pooled
      audit results showed statistically significant improvements in seven out of nine
      clinical processes. CONCLUSIONS: The findings indicate an association between the
      application of clinical audit and quality improvement in resource-limited
      settings. Co-interventions introduced after the baseline audit are likely to have
      contributed to improved outcomes. In addition, support from the relevant
      government health programmes and commitment of managers and frontline staff
      contributed to the audit's success.

PMID- 23118095
TI  - Comparison of health service accreditation programs in low- and middle-income
      countries with those in higher income countries: a cross-sectional study.
AB  - OBJECTIVE: The study aim was twofold: to investigate and describe the
      organizational attributes of accreditation programmes in low- and middle-income
      countries (LMICs) to determine how or to what extent these differ from those in
      higher-income countries (HICs) and to identify contextual factors that sustain or
      are barriers to their survival. DESIGN: Web-based questionnaire survey.
      PARTICIPANTS: National healthcare accreditation providers and those offering
      international services. In total, 44 accreditation agencies completed the survey.
      MAIN OUTCOME MEASURE(S): Income distinctions, accreditation programme features,
      organizational attributes and cross-national divergence. RESULTS: Accreditation
      programmes of LMICs exhibit similar characteristics to those of HICs. The
      consistent model of accreditation worldwide, centres on promoting improvements,
      applying standards and providing feedback. Where they do differ, the divergence
      is over specialized features rather than the general logic. LMICs were less
      likely than HICs to include an evaluation component to programmes, more likely to
      have certification processes for trainee surveyors and more likely to make
      decisions on the accreditation status based on a formulaic, mathematically
      oriented approach. Accreditation programme sustainability, irrespective of
      country characteristics, is influenced by ongoing policy support from government,
      a sufficient large healthcare market size, stable programme funding, diverse
      incentives to encourage participation in accreditation by Health Care
      Organizations as well as the continual refinement and improvement in
      accreditation agency operations and programme delivery. CONCLUSIONS:
      Understanding the similarities, differences and factors that sustain
      accreditation programmes in LMICs, and HICs, can be applied to benefit programmes
      around the world. A flourishing accreditation programme is one element of the
      institutional basis for high-quality health care.

PMID- 23118096
TI  - Quality of care in low- and middle-income settings: what next?

PMID- 23118097
TI  - A nationwide quality improvement project to accelerate Ghana's progress toward
      Millennium Development Goal Four: design and implementation progress.
AB  - QUALITY PROBLEM: The gap between evidence-based guidelines and practice of care
      is reflected, in low- and middle-income countries, by high rates of maternal and
      child mortality and limited effectiveness of large-scale programing to decrease
      those rates. CHOICE OF SOLUTION: We designed a phased, rapid, national scale-up
      quality improvement (QI) intervention to accelerate the achievement of Millennium
      Development Goal Four in Ghana. Our intervention promoted systems thinking,
      active participation of managers and frontline providers, generation and testing
      of local change ideas using iterative learning from transparent district and
      local data, local ownership and sustainability. IMPLEMENTATION: After 50 months
      of implementation, we have completed two prototype learning phases and have begun
      regional spread phases to all health facilities in all 38 districts of the three
      northernmost regions and all 29 Catholic hospitals in the remaining regions of
      the country. To accelerate the spread of improvement, we developed 'change
      packages' of rigorously tested process changes along the continuum of care from
      pregnancy to age 5 in both inpatient and outpatient settings. LESSONS LEARNED:
      The primary successes for the project so far include broad and deep adoption of
      QI by local stakeholders for improving system performance, widespread
      capacitation of leaders, managers and frontline providers in QI methods,
      incorporation of local ideas into change packages and successful scale-up to
      approximately 25% of the country's districts in 3 years. Implementation
      challenges include variable leadership uptake and commitment at the district
      level, delays due to recruiting and scheduling barriers, weak data systems and
      repeated QI training due to high staff turnover.

PMID- 23118098
TI  - Male urogenital disorders.

PMID- 23118099
TI  - High dose rate prostate brachytherapy: an overview of the rationale, experience
      and emerging applications in the treatment of prostate cancer.
AB  - The technological advances in real-time ultrasound image guidance for high dose
      rate (HDR) prostate brachytherapy places this treatment modality at the forefront
      of innovation in radiotherapy. This review article will explore the rationale for
      HDR brachytherapy as a highly conformal method of dose delivery and safe dose
      escalation to the prostate, in addition to the particular radiobiological
      advantages it has over low dose rate and external beam radiotherapy. The
      encouraging outcome data and favourable toxicity profile will be discussed before
      looking at emerging applications for the future and how this procedure will
      feature alongside stereotactic radiosurgery.

PMID- 23118101
TI  - Investigation of erectile dysfunction.
AB  - Erectile dysfunction (ED) represents a common and debilitating condition with a
      wide range of organic and non-organic causes. Physical aetiologies can be divided
      into disorders affecting arterial inflow, the venous occlusion mechanism or the
      penile structure itself. Various imaging modalities can be utilised to
      investigate the physical causes of ED, but penile Doppler sonography (PDS) is the
      most informative technique, indicated in those patients with ED who do not
      respond to oral pharmacological agents (e.g. phosphodiesterase type 5
      inhibitors). This review will examine the anatomical and physiological basis of
      penile erection, the method for performing PDS and features of specific causes of
      ED, and will also consider the alternative imaging modalities available.

PMID- 23118100
TI  - Current management of prostate cancer: dilemmas and trials.
AB  - The past decade has witnessed significant advances in our understanding of the
      biology of prostate cancer. Androgen ablation/androgen receptor inhibition
      remains as the mainstay of treatment for advanced prostate cancer. Our
      understanding of the biology of prostate cancer has increased exponentially owing
      to advances in molecular biology. With this knowledge many intriguing issues have
      come to light, which clinicians and scientists alike strive to answer. These
      include why prostate cancer is so common, what drives the development of prostate
      cancer at a molecular level, why prostate cancer appears refractory to many
      families of cytotoxic chemotherapeutics, and why prostate cancer preferentially
      metastasizes to bone. Two clinical forms of prostate cancer have been identified:
      indolent organ confined disease, which elderly men often die of, and aggressive
      metastatic disease. A method of distinguishing between these two forms of the
      disease at an organ-confined stage remains elusive. Understanding the mechanisms
      of castrate resistance is a further issue of clinical importance. New trials of
      treatments, including molecular agents that target prostate cancer from a range
      of angles, have been instituted over the past 10-15 years. We can look at these
      trials not only as a chance to investigate the effectiveness of new treatments
      but also as an opportunity to further understand the complex biology of this
      disease.

PMID- 23118102
TI  - MRI of the penis.
AB  - MRI of the penis is an expensive test that is not always superior to clinical
      examination or ultrasound. However, it shows many of the important structures,
      and in particular the combination of tumescence from intracavernosal alprostadil,
      and high-resolution T(2) sequences show the glans, corpora and the tunica
      albuginea well. In this paper we summarise the radiological anatomy and discuss
      the indications for MRI. For penile cancer, it may be useful in cases where the
      local stage is not apparent clinically. In priapism, it is an emerging technique
      for assessing corporal viability, and in fracture it can in most cases make the
      diagnosis and locate the injury. In some cases of penile fibrosis and Peyronie's
      disease, it may aid surgical planning, and in complex pelvic fracture may replace
      or augment conventional urethrography. It is an excellent investigation for the
      malfunctioning penile prosthesis.

PMID- 23118103
TI  - Underestimating the safety benefits of a new vaccine: the impact of acellular
      pertussis vaccine versus whole-cell pertussis vaccine on health services
      utilization.
AB  - The population-level safety benefits of the acellular pertussis vaccine may have
      been underestimated because only specific adverse events were considered, not
      overall impact on health services utilization. Using the Vaccine and Immunization
      Surveillance in Ontario (VISION) system, the authors analyzed data on 567,378
      children born between April 1994 and March 1996 (before introduction of acellular
      pertussis vaccine) and between April 1998 and March 2000 (after introduction of
      acellular pertussis vaccine) in Ontario, Canada. Using the self-controlled case
      series study design, they examined emergency room visits and hospital admissions
      occurring after routine pediatric vaccinations. The authors determined the
      relative incidence of events taking place before introduction of the acellular
      vaccine versus after introduction by calculating relative incidence ratios
      (RIRs). The observed RIRs demonstrated a highly statistically significant
      reduction in relative incidence after introduction of the acellular vaccine. RIRs
      for vaccine administered at ages 2, 4, 6, and 18 months were 1.82 (95% confidence
      interval (CI): 1.64, 2.01), 1.91 (95% CI: 1.71, 2.13), 1.54 (95% CI: 1.38, 1.72),
      and 1.51 (95% CI: 1.34, 1.69), respectively, comparing event rates before the
      introduction of acellular vaccine with those after introduction. The authors
      estimated that approximately 90 emergency room visits and 9 admissions per month
      were avoided by switching to the acellular vaccine, which is a 38-fold higher
      impact than when they considered only admissions for febrile and afebrile
      convulsions. Future analyses comparing vaccines for safety should examine
      specific endpoints and general health services utilization.

PMID- 23118104
TI  - 25-hydroxyvitamin D status and change in physical performance and strength in
      older adults: the Health, Aging, and Body Composition Study.
AB  - Low 25-hydroxyvitamin D (25(OH)D) concentrations are common among older adults
      and are associated with poorer physical performance and strength, but results
      from longitudinal studies have been inconsistent. The 25(OH)D threshold for
      physical performance and strength was determined, and both cross-sectional and
      longitudinal associations between 25(OH)D and physical performance and strength
      were examined, in men and women aged 71-80 years from the Health, Aging, and Body
      Composition Study (n = 2,641). Baseline serum 25(OH)D was measured in 1998-1999,
      and physical performance and strength were measured at baseline and at 2- and 4
      year follow-up. Piecewise regression models were used to determine 25(OH)D
      thresholds. Linear regression and mixed models were used to examine cross
      sectional and longitudinal associations. The 25(OH)D thresholds were 70-80 nmol/L
      for physical performance and 55-70 nmol/L for strength. Participants with 25(OH)D
      <50 nmol/L had poorer physical performance at baseline and at 2- and 4-year
      follow-up than participants with 25(OH)D >=75 nmol/L (P < 0.01). Although
      physical performance and strength declined over 4 years of follow-up (P <
      0.0001), in general, the rate of decline was not associated with baseline
      25(OH)D. Older adults with low 25(OH)D concentrations had poorer physical
      performance over 4 years of follow-up, but low 25(OH)D concentrations were not
      associated with a faster rate of decline in physical performance or strength.

PMID- 23118105
TI  - Likelihood ratio test for detecting gene (G)-environment (E) interactions under
      an additive risk model exploiting G-E independence for case-control data.
AB  - There has been a long-standing controversy in epidemiology with regard to an
      appropriate risk scale for testing interactions between genes (G) and
      environmental exposure (E ). Although interaction tests based on the logistic
      model-which approximates the multiplicative risk for rare diseases-have been more
      widely applied because of its convenience in statistical modeling, interactions
      under additive risk models have been regarded as closer to true biologic
      interactions and more useful in intervention-related decision-making processes in
      public health. It has been well known that exploiting a natural assumption of G-E
      independence for the underlying population can dramatically increase statistical
      power for detecting multiplicative interactions in case-control studies. However,
      the implication of the independence assumption for tests for additive interaction
      has not been previously investigated. In this article, the authors develop a
      likelihood ratio test for detecting additive interactions for case-control
      studies that incorporates the G-E independence assumption. Numerical
      investigation of power suggests that incorporation of the independence assumption
      can enhance the efficiency of the test for additive interaction by 2- to 2.5
      fold. The authors illustrate their method by applying it to data from a bladder
      cancer study.

PMID- 23118106
TI  - Splice isoforms as therapeutic targets for colorectal cancer.
AB  - Alternative pre-mRNA splicing allows exons of pre-mRNA to be spliced in different
      arrangements to produce functionally distinct mRNAs. More than 95% of human genes
      encode splice isoforms, some of which exert antagonistic functions. Recent
      studies revealed that alterations of the splicing machinery can cause the
      development of neoplasms, and understanding the splicing machinery is crucial for
      developing novel therapeutic strategies for malignancies. Colorectal cancer
      patients need novel strategies not only to enhance the efficacy of the currently
      available agents but also to utilize newly identified therapeutic targets. This
      review summarizes the current knowledge about the splice isoforms of VEGFA,
      UGT1A, PXR, cyclin D1, BIRC5 (survivin), DPD, K-RAS, SOX9, SLC39A14 and other
      genes, which may be possible therapeutic targets for colorectal cancer. Among
      them, the VEGFA splice isoforms are classified into VEGFAxxx and VEGFAxxxb, which
      have proangiogenic and antiangiogenic properties, respectively; UGT1A is
      alternatively spliced into UGT1A1 and other isoforms, which are regulated by
      pregnane X receptor isoforms and undergo further splicing modifications.
      Recently, the splicing machinery has been extensively investigated and novel
      discoveries in this research field are being reported at a rapid pace. The
      information contained in this review also provides suggestions for how
      therapeutic strategies targeting alternative splicing can be further developed.

PMID- 23118107
TI  - Is vasculopathy associated with systemic sclerosis more severe in men?
AB  - OBJECTIVE: To identify possible differences in morbidity and mortality between
      men and women with systemic sclerosis (SSc) by examining a homogeneous cohort at
      a single academic center. METHODS: Demographic, clinical, and outcome data for
      all 231 patients of Greek origin with SSc who were examined between 1995 and 2011
      in our department (200 women) were recorded in consecutive 3-year intervals from
      disease onset; data were analyzed retrospectively. RESULTS: Factors comparable
      between sexes were age (yrs +/- SD) at disease onset (46 +/- 15 vs 46 +/- 15),
      diffuse skin involvement (61.3% of men vs 46.4% of women), and anti-Scl-70
      antibody positivity (66.6% of men vs 59.2% of women). Also comparable were
      prevalence of interstitial lung disease, upper or lower gastrointestinal (GI)
      tract involvement, and echocardiographic findings during the first, second, and
      third 3-year intervals from disease onset (2904 patient-yrs). In contrast,
      vasculopathy occurred earlier in men. During the first 3 years digital ulcers
      developed in 54% of men versus 31% of women (p = 0.036) and renal crisis
      developed in 17% of men versus 3% of women (p = 0.006). No significant
      differences regarding social history, smoking, medical history, or disease
      management were identified. After excluding non-SSc-related deaths, survival was
      worse in men (p = 0.005, Kaplan-Meier analysis) with significantly lower 6- and
      12-year cumulative rates (77.2% and 53.8%, respectively, in men vs 97.3% and
      89.2% in women). CONCLUSION: Results derived from an unselected SSc population
      indicate that the disease is more severely expressed in men than in women, a
      finding that could be related to more rapid development of vasculopathy in men.
      Studies are warranted in other single-center cohorts to confirm these findings.

PMID- 23118108
TI  - Development and assessment of users' satisfaction with the systemic lupus
      erythematosus disease activity index 2000 responder index-50 website.
AB  - OBJECTIVE: To describe the development of the Systemic Lupus Erythematosus
      Disease Activity Index 2000 Responder Index-50 (S2K RI-50) Website (www.s2k-ri
      50.com) and to assess satisfaction with its training and examination modules
      among rheumatologists and rheumatology fellows. METHODS: The development of the
      Website occurred in 3 phases. The first was a deployment phase that consisted of
      preparing the site map along with its content. The content included the S2K RI-50
      training manual, the tests and corresponding question bank, and the online
      adaptive training module, along with the extensive site testing. The second phase
      included the participation of rheumatologists and trainees who completed the
      Website modules. The third was a quality assurance phase in which an online
      survey was developed to determine the satisfaction level of its users. Further
      modifications were implemented per participants' recommendations. RESULTS: The
      site has been online since it was registered in September 2010. Fourteen
      rheumatologists and rheumatology trainees from different centers reviewed and
      completed the material contained in the Website. The survey revealed acceptance
      among rheumatologists for the Website's content, design, and presentation. The
      Website was rated as user-friendly and useful in familiarizing investigators with
      the S2K RI-50. After completion of the training and examination modules,
      participants reported a suitable level of preparation to implement the S2K RI-50
      in clinical trials and research settings in a timely manner. CONCLUSION: The
      Website includes training and examination modules that familiarize
      rheumatologists with the S2K RI-50 and assesses their competence to use the
      index. This prepares them for the use of the S2K RI-50 in clinical trials and
      research settings.

PMID- 23118109
TI  - Consensus statements for the use of administrative health data in rheumatic
      disease research and surveillance.
AB  - OBJECTIVE: Administrative data are increasingly being used for research and
      surveillance about rheumatic diseases. However, literature reviews have revealed
      a lack of consistency in methods for conducting observational rheumatic disease
      studies, a situation that can lead to findings that cannot be compared. Our
      purpose was to develop best-practice consensus statements about the use of
      administrative data for rheumatic disease research and surveillance in Canada.
      METHODS: We convened 52 decision makers, epidemiologists, clinicians, and
      researchers to a 2-day workshop. Prior to this, participants formed working
      groups to examine 3 best-practice categories: case definitions, epidemiology
      methods, and comorbidity and outcomes measurement. The groups conducted
      systematic or scoping reviews on key topics. At the workshop, evidence from the
      reviews was presented and consensus-building techniques were used to develop the
      best-practice statements. The statements were presented, discussed, revised (as
      needed), and then subjected to voting. RESULTS: Thirteen best-practice consensus
      statements were developed and endorsed by consensus. For the first category,
      these consensus statements addressed validation techniques for rheumatic disease
      case definitions and case ascertainment bias. The consensus statements for
      epidemiology methods focused on confounding and drug exposure measurement. For
      comorbidity and outcomes measurement, consensus statements were developed for
      multiple conditions, including osteoporosis and fragility fractures, cancer,
      infections, cardiovascular disease, and renal disease. Strengths and limitations
      of administrative data were identified in relation to each topic. CONCLUSION: Our
      best-practice consensus statements are consistent with other recent guidelines,
      including those for rheumatic disease biologics registries, but address
      additional issues specific to administrative data. Continuing work focuses on
      disseminating these consensus statements to multiple audiences.

PMID- 23118110
TI  - Safety and efficacy of infliximab and adalimumab for refractory uveitis in
      juvenile idiopathic arthritis: 1-year followup data from the Italian Registry.
AB  - OBJECTIVE: To evaluate safety and efficacy of adalimumab (ADA) and infliximab
      (IFX) for the treatment of juvenile idiopathic arthritis-related anterior uveitis
      (JIA-AU). METHODS: Starting January 2007, patients with JIA-AU treated with IFX
      and ADA were managed by a standard protocol and data were entered into the
      National Italian Registry (NIR). At baseline, all patients were refractory to
      standard immunosuppressive treatment and/or were corticosteroid-dependent. Data
      recorded every 3 months included uveitis course, number/type of ocular
      complications, drug-related adverse events (AE), treatment change or withdrawal,
      and laboratory measures. Data of patients treated for at least 1 year were
      retrieved from the NIR and analyzed using descriptive statistics. Treatment
      efficacy was based on change in uveitis course and in number of ocular
      complications. RESULTS: Up to December 2009, data for 108 patients with JIA-AU
      treated with anti-tumor necrosis factor-alpha agents were recorded in the NIR and
      data from 91, with at least 12 months' followup, were included in the study.
      Forty-eight patients were treated with IFX, 43 with ADA. Forty-seven patients
      (55.3%) achieved remission of AU, 28 (32.9%) had recurrent AU, and 10 (11.8%)
      maintained a chronic course. A higher remission rate was observed with ADA (67.4%
      vs 42.8% with IFX; p = 0.025). Ocular complications decreased from 0.47 to 0.32
      per subject. Five patients experienced resolution of structural complications. No
      patient reported serious AE; 8 (8.8%) experienced 11 minor AE (9 with IFX, 2 with
      ADA). CONCLUSION: IFX and ADA appear to be effective and safe for treatment of
      refractory JIA-related uveitis, with a better performance of ADA in the medium
      term period.

PMID- 23118111
TI  - Reliability and longitudinal validity of computer-assisted methods for measuring
      joint damage progression in subjects with rheumatoid arthritis.
AB  - OBJECTIVE: To compare the metric properties of a computer-assisted erosion
      segmentation volume measurement with scoring using the Rheumatoid Arthritis
      Magnetic Resonance Imaging Score (RAMRIS) in a longitudinal cohort of patients
      with rheumatoid arthritis (RA). METHODS: Thirty-two sets of baseline and 2-year
      followup magnetic resonance imaging (MRI) of metacarpal phalangeal 2-5 joints of
      patients with RA were scored using RAMRIS and segmented using OSIRIS software.
      The smallest detectable difference (SDD), standardized response mean (SRM), and
      paired t-test were used to evaluate the sensitivity to change. Eleven of the 32
      patients' MRI were segmented by both readers to evaluate interreader agreement.
      The 28-joint Disease Activity Score (DAS28) and Sharp erosion scores further
      evaluated construct and longitudinal validity. RESULTS: Reliability of erosion
      progression by computer-assisted volume measurement was superior to RAMRIS
      [intrareader interclass correlation coefficient (ICC) 0.97 (0.94-0.99) vs 0.52
      (0.22-0.73)] and interreader ICC of volume measurement was 0.85 (0.53-0.96).
      Computer-assisted volume measurements identified 10 of 32 patients who progressed
      more than the SDD progression, whereas RAMRIS identified only 4 of 32 patients (p
      = 0.0013). By a paired t-test, however, all MRI measures progressed significantly
      over 2 years (irrespective of treatment arm) and there was little difference by
      SRM. Construct correlational validity of the MRI methods was 0.47-0.90 for status
      scores and 0.33-0.81 for progression. There was no relationship between the
      average DAS28 and erosion progression by any imaging method. CONCLUSION: Computer
      assisted measurement of erosion volume has good performance metrics. It had
      excellent intrareader and interreader reliability and was more sensitive to
      change than RAMRIS in this group of patients. www.ClinicalTrials.gov,
      NCT00451971.

PMID- 23118112
TI  - Fascin-expressing dendritic cells dominate in polymyositis and dermatomyositis.
AB  - OBJECTIVE: Dendritic cells (DC) have been reported among inflammatory
      infiltrating cells in muscle tissue in idiopathic inflammatory myopathies (IIM),
      but to our knowledge no studies concerning the expression of langerin (CD207) or
      fascin (markers of immature and mature DC, respectively) in IIM have been
      published. METHODS: Immunohistochemical analyses of langerin and fascin
      expression were performed on specimens from normal muscles, as well as those
      affected by polymyositis (PM) and dermatomyositis (DM). The results were analyzed
      by Mann-Whitney U test. RESULTS: In PM and DM, fascin-positive cells were
      numerous in the majority of the studied samples in perimysial, endomysial, and
      perivascular cellular infiltrates. Sporadic langerin-positive cells were
      detected. CONCLUSION: Fascin-positive DC predominance in inflammatory infiltrates
      in myositic muscles confirms the prevalence of mature forms and indicates that
      there are conditions stimulating DC maturation in both PM and DM. The induction
      of immunological tolerance by inhibiting DC maturation may be a promising
      direction for studies of myositis treatment.

PMID- 23118113
TI  - Quantitative radiographic features of early knee osteoarthritis: development over
      5 years and relationship with symptoms in the CHECK cohort.
AB  - OBJECTIVE: To evaluate whether computer-assisted, interactive digital analysis of
      knee radiographs enables identification of different quantitative features of
      joint damage, and to evaluate the relationship of such features with each other
      and with clinical characteristics during 5-year followup in early osteoarthritis
      (OA). METHODS: Knee radiographs from the Cohort Hip and Cohort Knee (CHECK)
      study, including 1002 individuals with early OA complaints, were evaluated for
      different measures with knee images digital analysis (KIDA). To aid definition of
      different radiographic features of OA, principal component analysis of KIDA was
      used. Features were correlated (Pearson) to each other, evaluated for changes
      over time, and related to clinical outcome (Western Ontario and McMaster
      Universities Osteoarthritis Index for pain and function) using baseline, 2-year,
      and 5-year followup data. RESULTS: The identified radiographic features were
      joint space width (JSW: minimum, medial, lateral), varus angle, osteophyte area,
      eminence height, and bone density. The features progressed in severity at
      different times during followup: early (medial JSW, osteophyte area), late
      (minimum and lateral JSW, eminence height), and both early and late (varus angle,
      bone density). Correlations between different radiographic features varied
      between timepoints. The JSW features were most strongly related to each other
      (largest r = 0.82), but also, e.g., osteophytes and bone density were correlated
      (largest r = 0.33). The relationships with clinical outcome varied over time, but
      were most commonly found for osteophyte area and JSW. CONCLUSION: In this early
      OA cohort, different radiographic features were identified that progressed at
      different rates between timepoints. The relations between radiographic features
      and with clinical outcome varied over time. This implies that longitudinal
      evaluation of different features can improve insight into progression of OA.

PMID- 23118114
TI  - Longterm effects of endothelin receptor antagonism on microvascular damage
      evaluated by nailfold capillaroscopic analysis in systemic sclerosis.
AB  - OBJECTIVE: Systemic sclerosis (SSc) is characterized by microvascular injury,
      fibrosis, and hypoxia of involved tissues. The vasoactive peptide endothelin-1
      (ET-1) seems to be implicated in these events. Using nailfold videocapillaroscopy
      (NVC), we evaluated longterm effects of ET-1 antagonist treatment on nailfold
      microvascular damage in patients with SSc, over a 3-year followup period.
      METHODS: Thirty patients with SSc (mean age 64 +/- 5 yrs, mean disease duration 8
      +/- 1 yrs) were recruited during their programmed standard treatment protocols.
      At baseline (T0), 15 patients with SSc (mean age 63 +/- 15 yrs, mean disease
      duration 7 +/- 3 yrs), already receiving cyclic intravenous infusion of iloprost
      (5 continuous days, average 80 MUg/day, every 3 mo), continued the treatment for
      a further 3 years (ILO group). The remaining 15 patients with SSc (mean age 68 +/
      13 yrs, mean disease duration 8 +/- 4 yrs), although they continued the same
      cyclic intravenous iloprost treatment as the previous group, also received
      bosentan 125 mg twice a day for 3 years (ILO+BOS group). Qualitative analysis
      (scleroderma patterns) and semiquantitative scoring of the microvascular damage
      were performed by validated routine NVC methods. RESULTS: During followup, a
      statistically significant increase of capillary number was observed in the
      ILO+BOS group (p < 0.02), with a significant and progressive increase of
      angiogenesis (p < 0.01). In contrast, the ILO group showed a statistically
      significant decrease of capillary number (p < 0.05). After 3 years the number of
      capillaries was significantly higher in the ILO+BOS group than in the ILO group
      (p < 0.05). The score for giant capillaries decreased significantly in both
      groups of patients with SSc (p < 0.05). CONCLUSION: In this open study, longterm
      treatment with ET-1 receptor antagonist in combination with iloprost was found to
      interfere with progression of nailfold microvascular damage in patients with SSc,
      as assessed by NVC over a 3-year followup period.

PMID- 23118115
TI  - Methotrexate and injectable tumor necrosis factor-alpha inhibitor adherence and
      persistence in children with rheumatic diseases.
AB  - OBJECTIVE: To measure adherence and persistence with methotrexate (MTX) and
      injectable tumor necrosis factor-alpha (iTNF-alpha) inhibitors (etanercept,
      adalimumab) among children prescribed these medications by a rheumatologist.
      METHODS: Data were obtained from a US pharmacy benefits management firm. Children
      were included if they were < 18 years of age, had >= 1 prescription claim between
      January 2009 and December 2010 for MTX or an iTNF-alpha inhibitor that was
      prescribed by an adult or pediatric rheumatologist. The medication possession
      ratio (MPR) was calculated for each medication, with MPR >= 80% indicating good
      adherence. MPR were compared by route of administration, age, and by new users
      versus continuing users. Persistence was measured for new users of each
      medication from initiation until discontinuation, or for a maximum of 1 year.
      RESULTS: A total of 1964 children were included. The majority of children had MPR
      < 80%. Children taking subcutaneous MTX had the lowest mean MPR [46.9%; median
      44.9%; interquartile range (IQR) 23%-69.6%] and the lowest persistence, with 26%
      of children continuing the medication at 1 year. Mean MPR was highest for iTNF
      alpha (65.7%; median 70.1%; IQR 46%-89.3%), as was persistence, with 52% of
      children continuing the medication at 1 year. Children age < 13 years tended to
      have higher MPR, but this was statistically significant only for oral MTX (61.1%
      vs 54.9% in children age >= 13 yrs; p = 0.02). CONCLUSION: Adherence and
      persistence in this cohort varied by medication and route of administration. Both
      outcomes are important considerations for physicians prescribing these
      medications in routine clinical care and for the assessment of treatment
      effectiveness in the research setting.

PMID- 23118116
TI  - Two-year results of an open pilot study of a 2-treatment course with rituximab in
      patients with early systemic sclerosis with diffuse skin involvement.
AB  - OBJECTIVE: To study safety and potential efficacy of a 2-treatment course (month
      0/6) with rituximab (RTX) in early diffuse systemic sclerosis (dcSSc). METHODS:
      Two years' followup (open-label study) was done of 8 patients with early dcSSc.
      Patients received an infusion of 1000 mg RTX 2 times at months 0 and 6, with 100
      mg methylprednisolone. Clinical measurements, Disease Activity Score, functional
      status, and CD19+ peripheral blood count were performed at months 0, 3, 6, 12,
      15, 18, and 24 and histopathological evaluation of the skin at months 0, 3, 12,
      and 24. RESULTS: There was a clinically significant change in skin score, with a
      mean Modified Rodnan skin score of 24.8 at baseline (SD 3.4) and 13.6 at Month 24
      [SD 5.6; mixed models analyses (MMA) p < 0.0001] and a significant decrease in
      Disease Activity Score (DAS), with a median of 4.5 at baseline (range 1.5-7.5)
      and 0.5 at Month 24 (range 0.0-5.5; MMA p < 0.0001). Indices of internal organ
      involvement remained stable throughout the study. RTX induced effective B cell
      depletion at baseline and Month 6 (< 5 CD19+ cells/MUl blood). The blindly
      assessed hyalinized collagen score changed significantly over time (MMA p =
      0.009), with a mean of 69.3 at baseline (SD 22.8) and 33.1 at 24 months (SD
      27.0). Five serious adverse events were considered unrelated to the RTX
      treatment. CONCLUSION: A 2-treatment course (months 0/6) with RTX appears to be
      well tolerated and may have potential efficacy for skin disease and stabilization
      of internal organ status in early dcSSc. Clinical Trials Registration
      NCT00379431.

PMID- 23118117
TI  - Do structural changes (eg, collagen/matrix) explain the response to therapeutic
      exercises in tendinopathy: a systematic review.
AB  - BACKGROUND: Previous reviews have highlighted the benefit of loaded therapeutic
      exercise in the treatment of tendinopathy. Changes in observable structural
      outcomes have been suggested as a possible explanation for this response to
      therapeutic exercise. However, the mechanism for the efficacy of therapeutic
      exercise remains unclear. OBJECTIVE: To systematically review the relationship
      between the observable structural change and clinical outcomes following
      therapeutic exercise. DATA SOURCES: An electronic search of AMED, CiNAHL,
      Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PEDro and
      SPORTDiscus was undertaken from their inception to June 2012. STUDY ELIGIBILITY
      CRITERIA: Any study design that incorporated observable structural outcomes and
      clinical outcomes when assessing the effect of therapeutic exercise on
      participants with tendinopathy. STUDY APPRAISAL AND SYNTHESIS METHODS: Included
      studies were appraised for risk of bias using the tool developed by the Cochrane
      Back Review Group. Due to heterogeneity of studies, a qualitative synthesis was
      undertaken. RESULTS: Twenty articles describing 625 patients were included.
      Overall, there is a strong evidence to refute any observable structural change as
      an explanation for the response to therapeutic exercise when treated by eccentric
      exercise training. Moderate evidence does exist to support the response of heavy
      slow resistance training (HSR). CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: The
      available literature does not support observable structural change as an
      explanation for the response of therapeutic exercise except for some support from
      HSR. Future research should focus on indentifying other explanations including
      neural, biochemical and myogenic changes. REGISTRATION NUMBER: Registered with
      PROSPERO, registration number CRD42011001638.

PMID- 23118118
TI  - Sudden cardiac death screening in adolescent athletes: an evaluation of
      compliance with national guidelines.
AB  - OBJECTIVE: In the USA, the preparticipation physical evaluation (PPE) is the
      standard of care for screening eight million high-school athletes for their risk
      of sudden cardiac death (SCD). Our aim was to evaluate both physician and school
      compliance with national guidelines for SCD screening. METHODS: We conducted a
      confidential survey of the Washington Chapter of the American Academy of
      Pediatrics (AAP), the Washington Academy of Family Physicians (WAFP) and
      Washington State high-school athletic directors. Responses were evaluated for
      compliance with the American Heart Association (AHA) guidelines for SCD
      screening. RESULTS: We received a response rate of 72% (559/776) from the AAP,
      56% (554/990) from the WAFP and 78% (317/409) from the athletic directors. Only
      6% of all providers and 0% of schools were in compliance with AHA guidelines. In
      addition, 47% of the physicians and 6% of athletic directors reported awareness
      of the guidelines. There was no difference in compliance between physician
      specialties (p=0.20). Physician location, years of experience and exposure to SCD
      were not significantly associated with compliance. Provider knowledge of the
      guidelines, number of PPE/month and frequency of referrals to cardiology were all
      positively associated with improved overall compliance (p<0.05). CONCLUSIONS:
      Despite the unaltered presence of the AHA SCD screening guidelines for the past
      15 years, compliance with the recommendations is poor. Lack of compliance does
      not reflect clinical experience, but rather lack of knowledge of the guidelines
      themselves. New directions for provider education and policy requirements are
      needed to improve this implementation gap.

PMID- 23118119
TI  - Medical services at the first Winter Youth Olympic Games 2012 in
      Innsbruck/Austria.
AB  - BACKGROUND: The Youth Olympic Games (YOG) are a new format designed by the
      International Olympic Committee. So far no reference data are available regarding
      the organisation or implementation of the medical services that were needed for
      the Winter Youth Olympic Games that took place for the first time in Innsbruck 9
      24 January 2012. OBJECTIVES: (1) To provide insight into what is needed to
      prepare for such a complex high level sporting event from a medical perspective,
      (2) to provide data on medical services for future organising committees and (3)
      to provide information on different National Olympic Committee (NOC) delegation
      structures and the consequences of registering a National Olympic Committee Team
      Physician. METHODS: A medical information system in the form of a patient data
      management system was developed with all involved parties to standardise data
      collection. All medical encounters occurring at any IYOGOC medical service centre
      (including physiotherapy and psychology facilities) were tracked and collected in
      daily reports. Data evaluation was prepared based on different interest groups
      (Athletes, National Olympic Committees, Workforce, International Olympic
      Committee and Media) and analysed. RESULTS: 327 medical encounters (42.8%
      athletes; out of these, 57.9% were accounted to athletes with own NOC team
      physician) were seen during the YOG 2012. The total number of hospital transports
      was 27.3%, of which 8.9% were hospitalised with an average length of 1.9 nights.
      Physiotherapy usage was low with only 19 medical encounters resulting in a
      referral to physiotherapy accounting for 67 treatments during the entire YOG.
      Psychological care service was not used at all. The main reason for illnesses was
      disorders of the respiratory system (28.8%), injuries mostly affected upper
      extremities (49.6%) and were mostly diagnosed with lacerations and contusions
      (26.2%). Injury (70.7%) and illness (29.3%) incidences in athletes were slightly
      lower than previous studies showed. 40.0% of NOC delegations registered their own
      team physicians, which led to a significant difference in usage frequency of
      medical service (-3%, p=0.012). CONCLUSIONS: Medical service coverage at the
      first Winter Youth Olympic Games seemed to be appropriate. No disaster or
      epidemic disease challenged the medical service plan. Future organising
      committees could use the provided data as a reference for their planning efforts.

PMID- 23118120
TI  - Return to sports activity after tibial plateau fractures: 89 cases with minimum
      24-month follow-up.
AB  - BACKGROUND: Tibial plateau fractures requiring surgery are severe injuries. For
      professionals, amateurs, and recreational athletes, tibial plateau fractures
      might affect leisure and professional life. HYPOTHESIS: Athletic patients will be
      affected in their sporting activity after a tibial plateau fracture. Despite a
      long rehabilitation time and program, physical activity will change to low-impact
      sports. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 89
      consecutive patients (age range, 14-76 years) were included in the study and were
      surveyed by a questionnaire. Inclusion criteria were surgical treatment of tibial
      plateau fractures between 2003 and 2009 with a minimum follow-up of 24 months.
      The sporting activity was determined at the time of injury, 1 year
      postoperatively, and at the time of the survey at an average of 52.8 months
      postoperatively. The clinical evaluation included the Lysholm score, the Tegner
      activity scale, the activity rating scale (ARS), and a visual analog scale (VAS)
      for pain perception. Fractures were classified and analyzed using both the
      Arbeitsgemeinschaft fur Osteosynthesefragen (AO) and the Schatzker
      classifications. RESULTS: At the time of injury, 88.8% of all patients were
      engaged in sports compared with 62.9% 1 year postoperatively and 73.0% at the
      time of the survey. Of the professional or competitive athletes (n = 11 at the
      time of injury), only 2 returned to competition at the time of the survey. The
      number of different sporting activities declined from 4.9 at the time of injury
      to 3.6 at the time of the survey (P < .001). The sports frequency and the
      activity duration per week, being 2.8 sessions and 4.5 hours at the time of
      injury, respectively, declined to 2.4 sessions and 3.8 hours (P < .001 and P =
      .007, respectively) at the time of the survey, respectively. The Lysholm score
      (98.7 points before accident) and the VAS for pain perception (0.2 before
      accident) illustrated significant declines to 76.6 points for the Lysholm score
      and 2.6 for the VAS (P < .001 and P < .001, respectively) at the time of the
      survey. The high-energy traumas, Schatzker IV to VI, had significant worse
      results in the clinical scores compared with the low-energy traumas (Lysholm, P <
      .001; Tegner, P = .027). CONCLUSION: The majority of patients could not return to
      their previous level of activity, and for patients playing competitive sports,
      this injury can be a career ender. Overall, we noticed a postinjury shift toward
      activities with less impact. However, at the time of the survey, 73% of all
      patients were engaged in sports.

PMID- 23118121
TI  - Two-year follow-up study on clinical and radiological outcomes of polyurethane
      meniscal scaffolds.
AB  - BACKGROUND: Little is known about radial displacement (RD) of polyurethane (PU)
      scaffolds, intended for partial meniscus defect substitution; no data are
      available on whether rim thickness influences RD and whether RD correlates with
      clinical outcome scores. HYPOTHESES: The meniscus is not extruded preoperatively,
      but RD occurs after scaffold implantation. A thicker rim will limit RD, and there
      is no correlation between RD and clinical outcome. STUDY DESIGN: Case series;
      Level of evidence, 4. METHODS: Twenty-six patients were implanted with a PU
      scaffold (8 lateral, 18 medial). Radial displacement (mm) was evaluated on
      magnetic resonance images preoperatively and at 3 months, 1 year, and 2 years
      postoperatively. At each time point, it was determined whether a correlation
      existed between the rim and RD. Clinical outcome was determined using a visual
      analog scale (VAS) for pain as well as the Lysholm knee scoring scale, Knee
      Injury and Osteoarthritis Outcome Score (KOOS), and International Knee
      Documentation Committee (IKDC) score. RESULTS: Radial displacement of lateral
      scaffolds was not significantly different (P = .178) either preoperatively (mean
      +/- SD, 3.42 +/- 0.99 mm) or at 3 months (4.82 +/- 0.59 mm), 1 year (4.55 +/-
      0.87 mm), or 2 years postoperatively (4.10 +/- 0.93 mm). No correlation was
      observed between the rim and lateral RD at all time points. Medial scaffold RD
      increased significantly (P < .001) from preoperative values (2.17 +/- 0.84 mm) to
      those at 3 months (4.25 +/- 0.89 mm), 1 year (4.43 +/- 1.01 mm), and 2 years
      postoperatively (4.41 +/- 0.96 mm). A strong negative correlation between medial
      RD and the rim was observed at all time points. There was no significant
      correlation between clinical outcome scores and RD, either preoperatively or
      postoperatively. CONCLUSION: This study demonstrated that limited medial meniscal
      RD was present preoperatively but increased by 2 mm after scaffold implantation.
      Lateral RD was also present preoperatively but did not increase after scaffold
      implantation. Importantly, a strong negative correlation was found between the
      rim and postoperative medial RD; a thicker rim limited RD. However, in the
      lateral compartment, rim thickness did not correlate with RD because RD was
      already strongly present preoperatively. Finally, no correlations were observed
      between scaffold RD and clinical outcome scores, either preoperatively or
      postoperatively.

PMID- 23118122
TI  - Aluminium tolerance in rice is antagonistic with nitrate preference and
      synergistic with ammonium preference.
AB  - BACKGROUND AND AIMS: Acidic soils are dominated chemically by more ammonium and
      more available, so more potentially toxic, aluminium compared with neutral to
      calcareous soils, which are characterized by more nitrate and less available, so
      less toxic, aluminium. However, it is not known whether aluminium tolerance and
      nitrogen source preference are linked in plants. METHODS: This question was
      investigated by comparing the responses of 30 rice (Oryza sativa) varieties (15
      subsp. japonica cultivars and 15 subsp. indica cultivars) to aluminium, various
      ammonium/nitrate ratios and their combinations under acidic solution conditions.
      KEY RESULTS: indica rice plants were generally found to be aluminium-sensitive
      and nitrate-preferring, while japonica cultivars were aluminium-tolerant and
      relatively ammonium-preferring. Aluminium tolerance of different rice varieties
      was significantly negatively correlated with their nitrate preference.
      Furthermore, aluminium enhanced ammonium-fed rice growth but inhibited nitrate
      fed rice growth. CONCLUSIONS: The results suggest that aluminium tolerance in
      rice is antagonistic with nitrate preference and synergistic with ammonium
      preference under acidic solution conditions. A schematic diagram summarizing the
      interactions of aluminium and nitrogen in soil-plant ecosystems is presented and
      provides a new basis for the integrated management of acidic soils.

PMID- 23118124
TI  - Wisdom is knowing you know nothing.

PMID- 23118123
TI  - A paradigm shift towards low-nitrifying production systems: the role of
      biological nitrification inhibition (BNI).
AB  - BACKGROUND: Agriculture is the single largest geo-engineering initiative that
      humans have initiated on planet Earth, largely through the introduction of
      unprecedented amounts of reactive nitrogen (N) into ecosystems. A major portion
      of this reactive N applied as fertilizer leaks into the environment in massive
      amounts, with cascading negative effects on ecosystem health and function.
      Natural ecosystems utilize many of the multiple pathways in the N cycle to
      regulate N flow. In contrast, the massive amounts of N currently applied to
      agricultural systems cycle primarily through the nitrification pathway, a single
      inefficient route that channels much of this reactive N into the environment.
      This is largely due to the rapid nitrifying soil environment of present-day
      agricultural systems. SCOPE: In this Viewpoint paper, the importance of
      regulating nitrification as a strategy to minimize N leakage and to improve N-use
      efficiency (NUE) in agricultural systems is highlighted. The ability to suppress
      soil nitrification by the release of nitrification inhibitors from plant roots is
      termed 'biological nitrification inhibition' (BNI), an active plant-mediated
      natural function that can limit the amount of N cycling via the nitrification
      pathway. The development of a bioassay using luminescent Nitrosomonas to quantify
      nitrification inhibitory activity from roots has facilitated the characterization
      of BNI function. Release of BNIs from roots is a tightly regulated physiological
      process, with extensive genetic variability found in selected crops and pasture
      grasses. Here, the current status of understanding of the BNI function is
      reviewed using Brachiaria forage grasses, wheat and sorghum to illustrate how BNI
      function can be utilized for achieving low-nitrifying agricultural systems. A
      fundamental shift towards ammonium (NH4(+))-dominated agricultural systems could
      be achieved by using crops and pastures with high BNI capacities. When viewed
      from an agricultural and environmental perspective, the BNI function in plants
      could potentially have a large influence on biogeochemical cycling and closure of
      the N loop in crop-livestock systems.

PMID- 23118125
TI  - Commentary on: cardiac power index: staging heart failure for mechanical
      circulatory support.

PMID- 23118126
TI  - Commentary on: clinical and biochemical outcomes for additional mesenteric and
      lower body perfusion during hypothermic arrest for complex total aortic arch
      replacement surgery.

PMID- 23118127
TI  - Commentary on: intimal hyperplasia: slow but deadly.

PMID- 23118128
TI  - Decreased expression of gamma-carboxylase in diabetes-associated arterial
      stiffness: impact on matrix Gla protein.
AB  - AIMS: Arterial stiffness is accelerated in type 1 diabetic patients. Medial
      artery calcification (MAC) contributes to the development of arterial stiffness.
      Vitamin K oxidoreductase (VKOR) reduces the vitamin K required by gamma
      carboxylase to activate matrix gamma-carboxyglutamic acid (Gla) protein (MGP), an
      inhibitor of vascular calcification. This study aimed to evaluate the hypothesis
      that diabetes reduces the gamma-carboxylation of MGP in the aortic wall, leading
      to increased vascular calcification, and the role of gamma-carboxylase and VKOR
      in this gamma-carboxylation deficit. METHODS AND RESULTS: Type 1 diabetes was
      induced in male Wistar rats with a single ip injection of streptozotocin.
      Augmentation of arterial stiffness in diabetic rats was shown by a 44% increase
      in aortic pulse wave velocity. Aortic and femoral calcification were increased by
      26 and 56%, respectively. gamma-Carboxylated MGP (cMGP, active) was reduced by
      36% and the aortic expression of gamma-carboxylase was reduced by 58%. Expression
      of gamma-carboxylase correlated with cMGP (r= 0.59) and aortic calcification (r =
      -0.57). VKOR aortic expression and activity were not modified by diabetes.
      Vitamin K plasma concentrations were increased by 191% in diabetic rats. In ex
      vivo experiments with aortic rings, vitamin K supplementation prevented the
      glucose-induced decrease in gamma-carboxylase expression. CONCLUSION: Our results
      suggest that reduced cMGP, through an impaired expression of gamma-carboxylase,
      is involved in the early development of MAC in diabetes, and therefore, in the
      acceleration of arterial stiffness. A defect in vitamin K uptake by target cells
      could also be involved.

PMID- 23118129
TI  - SKA-31, a novel activator of SK(Ca) and IK(Ca) channels, increases coronary flow
      in male and female rat hearts.
AB  - AIMS: Endothelial SK(Ca) and IK(Ca) channels play an important role in the
      regulation of vascular function and systemic blood pressure. Based on our
      previous findings that small molecule activators of SK(Ca) and IK(Ca) channels
      (i.e. NS309 and SKA-31) can inhibit myogenic tone in isolated resistance
      arteries, we hypothesized that this class of compounds may induce effective
      vasodilation in an intact vascular bed, such as the coronary circulation. METHODS
      AND RESULTS: In a Langendorff-perfused, beating rat heart preparation, acute
      bolus administrations of SKA-31 (0.01-5 ug) dose-dependently increased total
      coronary flow (25-30%) in both male and female hearts; these responses were
      associated with modest, secondary increases in left ventricular (LV) systolic
      pressure and heart rate. SKA-31 evoked responses in coronary flow, LV pressure,
      and heart rate were qualitatively comparable to acute responses evoked by
      bradykinin (1 ug) and adenosine (10 ug). In the presence of apamin and TRAM-34,
      selective blockers of SK(Ca) and IK(Ca) channels, respectively, SKA-31 and
      bradykinin-induced responses were largely inhibited, whereas the adenosine
      induced changes were blocked by ~40%; TRAM-34 alone produced less inhibition.
      Sodium nitroprusside (SNP, 0.2 MUg bolus dose) evoked changes in coronary flow,
      LV pressure, and heart rate were similar to those induced by SKA-31, but were
      unaffected by apamin + TRAM-34. The NOS inhibitor L-NNA reduced bradykinin- and
      adenosine-evoked changes, but did not affect responses to either SKA-31 or SNP.
      CONCLUSION: Our study demonstrates that SKA-31 can rapidly and reversibly induce
      dilation of the coronary circulation in intact functioning hearts under basal
      flow and contractility conditions.

PMID- 23118130
TI  - CTLA4-IgG ameliorates homocysteine-accelerated atherosclerosis by inhibiting T
      cell overactivation in apoE(-/-) mice.
AB  - AIMS: Cytotoxic T lymphocyte antigen 4 (CTLA4) exerts inhibitory effects on T
      cell activation by competition with CD28. In this study, we investigated the
      effect of CTLA4-IgG on homocysteine (Hcy)-induced T-cell activation and potential
      signal pathways involved in atherosclerotic formation. METHODS AND RESULTS: The
      CD28 signal was significantly amplified by Hcy treatment in splenic T cells and
      hyperhomocysteinaemia (HHcy)-accelerated plaques in apolipoprotein E-deficient
      (apoE(-/-)) mice. As a major competitor of CD28, CTLA4-IgG (abatacept)
      pretreatment, 100 MUg/week, in apoE(-/-) mice could reverse 2- and 4-week HHcy
      accelerated atherosclerosis. Furthermore, the membrane level of CTLA4 was
      decreased and the endocytosis level was increased by HHcy. Endocytosed CTLA4
      molecules by Hcy were in large vesicles, colocalized with lysosomes and
      endosomes. Hcy-increased CTLA4 endocytosis and secretion of inflammatory
      cytokines in T cells were blocked by CTLA4-IgG and the PI3K inhibitor LY294002.
      Blocking the CD28 signal pathway in T cells significantly decreased Hcy-promoted
      macrophage migration. CONCLUSION: These results illustrate a novel mechanism of
      CD28-dependent T-cell costimulation involved in HHcy-accelerated atherosclerosis,
      which extends the pharmacological application of CTLA4-IgG for atherosclerosis.

PMID- 23118131
TI  - Myosin filament assembly onto myofibrils in live neonatal cardiomyocytes observed
      by TPEF-SHG microscopy.
AB  - AIMS: Understanding myofibrillogenesis is essential for elucidating heart muscle
      formation, development, and remodelling in response to physiological stimulation.
      Here, we report the dynamic assembly process of contractile myosin filaments onto
      myofibrils in a live cardiomyocyte culture during myofibrillogenesis. METHODS AND
      RESULTS: Utilizing a custom-built, two-photon excitation fluorescence and second
      harmonic generation imaging system equipped with an on-stage incubator, we
      observed new sarcomere additions in rat neonatal cardiomyocytes during 10 h of on
      stage incubation. The new sarcomere additions occurred at the side of existing
      myofibrils, where we observed mature myofibrils acting as templates, or at the
      interstice of several separated myofibrils. CONCLUSIONS: During sarcomeric
      addition, myosin filaments are assembled onto the premyofibril laterally. This
      lateral addition, which proceeds stepwise along the axial direction, plays an
      important role in the accumulation of Z-bodies to form mature Z-disks and in the
      regulation of sarcomeric alignment during maturation.

PMID- 23118132
TI  - Systems-level approaches reveal conservation of trans-regulated genes in the rat
      and genetic determinants of blood pressure in humans.
AB  - AIMS: Human genome-wide association studies (GWAS) of hypertension identified
      only few susceptibility loci with large effect that were replicated across
      populations. The vast majority of genes detected by GWAS has small effect and the
      regulatory mechanisms through which these genetic variants cause disease remain
      mostly unclear. Here, we used comparative genomics between human and an
      established rat model of hypertension to explore the transcriptional mechanisms
      mediating the effect of genes identified in 15 hypertension GWAS. METHODS AND
      RESULTS: Time series analysis of radiotelemetric blood pressure (BP) was
      performed to assess 11 parameters of BP variation in recombinant inbred strains
      derived from the spontaneously hypertensive rat. BP data were integrated with ~27
      000 expression quantative trait loci (eQTLs) mapped across seven tissues,
      detecting >8000 significant associations between eQTL genes and BP variation in
      the rat. We then compiled a large catalogue of human genes from GWAS of
      hypertension and identified a subset of 2292 rat-human orthologous genes.
      Expression levels for 795 (34%) of these genes correlated with BP variation
      across rat tissues: 51 genes were cis-regulated, whereas 459 were trans-regulated
      and enriched for 'calcium signalling pathway' (P = 9.6 * 10(-6)) and 'ion
      channel' genes (P = 3.5 * 10(-7)), which are important determinants of
      hypertension. We identified 158 clusters of trans-eQTLs, annotated the underlying
      'master regulator' genes and found significant over-representation in the human
      hypertension gene set (enrichment P = 5 * 10(-4)). CONCLUSION: We showed
      extensive conservation of trans-regulated genes and their master regulators
      between rat and human hypertension. These findings reveal that small-effect genes
      associated with hypertension by human GWAS are likely to exert their action
      through coordinate regulation of pathogenic pathways.

PMID- 23118133
TI  - Management of extra-articular fractures of the distal tibia: intramedullary
      nailing versus plate fixation.
AB  - Intramedullary nailing and plate fixation represent two viable approaches to
      internal fixation of extra-articular fractures of the distal tibia. Although both
      techniques have demonstrated success in maintaining reduction and promoting
      stable union, they possess distinct advantages and disadvantages that require
      careful consideration during surgical planning. Differences in soft-tissue health
      and construct stability must be considered when choosing between intramedullary
      nailing and plating of the distal tibia. Recent advances in intramedullary nail
      design and plate-and-screw fixation systems have further increased the options
      for management of these fractures. Current evidence supports careful
      consideration of the risk of soft-tissue complications, residual knee pain, and
      fracture malalignment in the context of patient and injury characteristics in the
      selection of the optimal method of fixation.

PMID- 23118134
TI  - Foot and ankle infections: diagnosis and management.
AB  - Infections of the foot are a common source of morbidity, disability, and
      potential limb loss. A large proportion of lower extremity infections occurs in
      the setting of diabetic neuropathy, with or without circulatory compromise, and
      are potentially preventable with regular surveillance. Adequate diagnosis and
      treatment of foot infections can be challenging. Successful treatment is
      dependent on factors such as etiology; vascular, neurologic, and immune status;
      and the identity of the offending organism.

PMID- 23118135
TI  - Radiologic assessment of spinal fusion.
AB  - Since surgical fusion of the spine was first described in 1911, multiple methods
      have been used to assess it. Although open surgical exploration remains the
      standard of care for determination of fusion, it is impractical in most clinical
      situations. Static radiographs have long been used as a practical method of
      fusion assessment, but they tend to significantly overestimate the presence of a
      solid fusion. Dynamic radiographs improve accuracy but limitations include
      measurement reliability, disagreement on allowable motion, and the two
      dimensional nature of radiographs. Ultimately, lack of movement at a fused
      segment does not confirm fusion. Radiostereometric analysis further improves
      accuracy; however, methodological demands make it largely impractical for routine
      use. CT is now widely accepted as the standard for noninvasive assessment of
      spinal fusion. Fine-cut imaging, multiplanar reconstruction, and metal artifact
      reduction have increased the ability to assess fusion on CT. However, significant
      concerns remain regarding the effects of high radiation exposure. Although MRI is
      appealing, its utility in assessing fusion remains unproven. Understanding the
      limitations of each technique allows judicious use of radiology in the assessment
      of spinal fusion.

PMID- 23118136
TI  - Posttraumatic elbow arthritis in the young adult: evaluation and management.
AB  - Degenerative joint disease following trauma to the elbow is difficult to manage
      in any patient. However, this condition becomes substantially more challenging in
      the young, active population. Increased activity demands and limited functional
      capacity of total elbow arthroplasty mean that joint arthroplasty should be
      regarded as a salvage procedure. The primary goal of treatment is to restore a
      pain-free or minimally painful functional joint while preserving future surgical
      options. This requires accurate assessment of the primary patient complaint, be
      it terminal pain and stiffness or pain along the entire arc of motion. Patients
      who report stiffness and pain at terminal motion may benefit from arthroscopic or
      open osteocapsular debridement. Those with advanced degenerative changes and pain
      throughout the entire arc of motion may require joint resurfacing with
      interposition arthroplasty, partial joint arthroplasty, or total joint
      arthroplasty.

PMID- 23118137
TI  - Benign tumors of the spine.
AB  - Benign tumors in the spine include osteoid osteoma, osteoblastoma, aneurysmal
      bone cyst, osteochondroma, neurofibroma, giant cell tumor of bone, eosinophilic
      granuloma, and hemangioma. Although some are incidental findings, some cause
      local pain, radicular symptoms, neurologic compromise, spinal instability, and
      deformity. The evaluation of spinal tumors includes a thorough history and
      physical examination, imaging, sometimes laboratory evaluation, and biopsy when
      indicated. Appropriate treatment may be observational (eg, eosinophilic
      granuloma) or ablative (eg, osteoid osteoma, neurofibroma, hemangioma), but
      generally is surgical, depending on the level of pain, instability, neurologic
      compromise, and natural history of the lesion. Knowledge of the epidemiology,
      common presentation, imaging, and treatment of benign bone tumors is essential
      for successful management of these lesions.

PMID- 23118138
TI  - Advances in wrist arthroscopy.
AB  - Since its introduction more than three decades ago, wrist arthroscopy has
      continually evolved. The procedure has a wide list of indications, including
      diagnostic and management applications. The scope of practice for the wrist
      arthroscopic surgeon includes management of triangulofibrocartilage complex
      pathology, evaluation and management of carpal instability, assistance in
      fracture reduction of the radius and scaphoid, treatment of trapeziometacarpal
      synovitis and arthritis, distal ulnar and carpal bone excisions, and salvage
      procedures. In addition, innovations such as new portals and smaller arthroscopes
      have expanded the applications of wrist arthroscopy.

PMID- 23118140
TI  - Neurodevelopment in children born to HIV-infected mothers by infection and
      treatment status.
AB  - BACKGROUND: We reviewed the impact of HIV, HIV exposure, and antiretroviral
      therapy/prophylaxis on neurodevelopmental outcomes of HIV-infected and HIV
      exposed-uninfected infants and children. METHODS: A literature search of Medline,
      Embase, PsychINFO, Web of Science, PubMed, and conference Web sites (1990-March
      2011) using the search terms, infant, child, HIV, neurodevelopment, cognition,
      language, and antiretroviral therapy, identified 31 studies of HIV/antiretroviral
      exposure using standardized tools to evaluate infant/child development as the
      main outcome. Articles were included if results were reported in children <16
      years of age who were exposed to HIV and antiretrovirals in fetal/early life, and
      excluded if children did not acquire HIV from their mothers or were not exposed
      to antiretrovirals in fetal/early life. RESULTS: Infants who acquired HIV during
      fetal and early life tended to display poorer mean developmental scores than HIV
      unexposed children. Mean motor and cognitive scores were consistently 1 to 2 SDs
      below the population mean. Mean scores improved if the infant received treatment
      before 12 weeks and/or a more complex antiretroviral regimen. Older HIV-infected
      children treated with highly active antiretroviral therapy demonstrated near
      normal global mean neurocognitive scores; subtle differences in language, memory,
      and behavior remained. HIV-exposed-uninfected children treated with
      antiretrovirals demonstrated subtle speech and language delay, although not
      universally. CONCLUSIONS: In comparison with resource-rich settings, HIV-infected
      and HIV-exposed-uninfected infants/children in resource-poor settings
      demonstrated greater neurodevelopmental delay compared with HIV-unexposed
      infants. The effects on neurodevelopment in older HIV-infected children commenced
      on antiretroviral therapy from an early age and HIV-exposed-uninfected children
      particularly in resource-poor settings remain unclear.

PMID- 23118141
TI  - Prone sleeping is a risk for SIDS, not for suffocation.

PMID- 23118142
TI  - The epidemiology of herpes zoster in patients with newly diagnosed cancer.
AB  - BACKGROUND: Given the limited literature, we conducted a study to examine the
      epidemiology of herpes zoster (HZ) among newly diagnosed cancer patients.
      METHODS: We identified adult health plan members of Kaiser Permanente Northern
      California diagnosed with invasive cancer from 2001 to 2005. Electronic health
      records with inpatient and outpatient diagnoses, laboratory tests, and antiviral
      medications were used to identify HZ diagnoses from 2001 to 2006. HZ diagnoses
      and associated complications were confirmed by medical chart review. Treatment
      with chemotherapy and corticosteroids was used to classify patients by
      immunosuppression level. RESULTS: Among 14,670 cancer patients, 424 were
      diagnosed with HZ during follow-up (median 22 months). The incidence of HZ was
      31/1,000 person-year (PY) in patients with hematologic malignancies and 12/1,000
      PY in patients with solid tumors. The corresponding 2-year cumulative incidence
      of HZ was approximately 6% and 2%, respectively. Compared with incidence rates of
      HZ reported in a general US population, the age- and sex-standardized rates of HZ
      were 4.8 times higher [95% confidence interval (CI), 4.0-5.6] in patients with
      hematologic malignancies and 1.9 times higher (95% CI, 1.7-2.1) in those with
      solid tumors. HZ risk increased with increasing level of immunosuppression. Among
      HZ cases, 19% with hematologic malignancies and 14% with solid tumors had HZ
      associated pain for at least 30 days. The corresponding numbers for nonpain
      related complications were 30% and 18%, respectively. CONCLUSIONS: Cancer
      patients are at substantially increased risk of HZ and among those with HZ,
      complications are relatively common. IMPACT: Better HZ prevention and treatment
      options for cancer patients are needed.

PMID- 23118143
TI  - A randomized controlled trial of a tailored navigation and a standard
      intervention in colorectal cancer screening.
AB  - BACKGROUND: This randomized, controlled trial assessed the impact of a tailored
      navigation intervention versus a standard mailed intervention on colorectal
      cancer screening adherence and screening decision stage (SDS). METHODS: Primary
      care patients (n = 945) were surveyed and randomized to a Tailored Navigation
      Intervention (TNI) Group (n = 312), Standard Intervention (SI) Group (n = 316),
      or usual care CONTROL GROUP (n = 317). TNI Group participants were sent
      colonoscopy instructions and/or stool blood tests according to reported test
      preference, and received a navigation call. The SI Group was sent both
      colonoscopy instructions and stool blood tests. Multivariable analyses assessed
      intervention impact on adherence and change in SDS at 6 months. RESULTS: The
      primary outcome, screening adherence (TNI Group: 38%, SI Group: 33%, CONTROL
      GROUP: 12%), was higher for intervention recipients than controls (P = 0.001 and
      P = 0.001, respectively), but the two intervention groups did not differ
      significantly (P = 0.201). Positive SDS change (TNI Group: +45%, SI Group: +37%,
      and CONTROL GROUP: +23%) was significantly greater among intervention recipients
      than controls (P = 0.001 and P = 0.001, respectively), and the intervention group
      difference approached significance (P = 0.053). Secondary analyses indicate that
      tailored navigation boosted preferred test use, and suggest that intervention
      impact on adherence and SDS was attenuated by limited access to screening
      options. CONCLUSIONS: Both interventions had significant, positive effects on
      outcomes compared with usual care. TNI versus SI impact had a modest positive
      impact on adherence and a pronounced effect on SDS. IMPACT: Mailed screening
      tests can boost adherence. Research is needed to determine how preference,
      access, and navigation affect screening outcomes.

PMID- 23118145
TI  - False positives in cancer epidemiology.
AB  - BACKGROUND: A recent attempt to estimate the false-positive rate for cancer
      epidemiology studies is based on agents in International Agency for Research on
      Cancer (IARC) category 3 (agent not classifiable as to its carcinogenicity to
      humans) in the IARC Monographs Program. METHODS: The estimation method is
      critiqued regarding biases caused by its reliance on the IARC classification
      criteria for assessing carcinogenic potential. RESULTS: The privileged position
      given to epidemiologic studies by the IARC criteria ensures that the percentage
      of positive epidemiologic studies for an agent will depend strongly on the IARC
      category to which the agent is assigned. Because IARC category 3 is composed of
      agents with the lowest-assessed carcinogenic potential to which the estimation
      approach in question could be applied, a spuriously low estimated false-positive
      rate was necessarily the outcome of this approach. CONCLUSIONS: Tendentious
      estimation approaches like that employed will by necessity produce spuriously low
      and misleading false positive rates. IMPACT: The recently reported estimates of
      the false-positive rate in cancer epidemiology are seriously biased and
      contribute nothing substantive to the literature on the very real problems
      related to false-positive findings in epidemiology.

PMID- 23118144
TI  - An analysis of the association between cancer-related information seeking and
      adherence to breast cancer surveillance procedures.
AB  - BACKGROUND: Breast cancer surveillance is important for women with a known
      history of breast cancer. However, relatively little is known about the
      prevalence and determinants of adherence to surveillance procedures, including
      associations with seeking of cancer-related information from medical and
      nonmedical sources. METHODS: We conducted a longitudinal cohort study of breast
      cancer patients diagnosed in Pennsylvania in 2005. Our main analyses included 352
      women who were eligible for surveillance and participated in both baseline (~1
      year after cancer diagnosis) and follow-up surveys. Outcomes were self-reported
      doctor visits and physical examination, mammography, and breast self-examination
      (BSE) at 1-year follow-up. RESULTS: Most women underwent two or more physical
      examinations according to recommended guidelines (85%). For mammography, 56% of
      women were adherent (one mammogram in a year) while 39% reported possible overuse
      (two or more mammograms). Approximately 60% of respondents reported regular BSE
      (>= 5 times in a year). Controlling for potential confounders, higher levels of
      cancer-related information seeking from nonmedical sources at baseline was
      associated with regular BSE (OR, 1.52; 95% CI, 1.01-2.29; P, 0.046). There was no
      significant association between information-seeking behaviors from medical or
      nonmedical sources and surveillance with physical examination or mammography.
      CONCLUSIONS: Seeking cancer-related information from nonmedical sources is
      associated with regular BSE, a surveillance behavior that is not consistently
      recommended by professional organizations. IMPACT: Findings from this study will
      inform clinicians on the contribution of active information seeking toward breast
      cancer survivors' adherence to different surveillance behaviors.

PMID- 23118147
TI  - Mycobacterium marinum infection in Drosophila melanogaster for antimycobacterial
      activity assessment.
AB  - OBJECTIVES: The major advantages of Drosophila melanogaster are a well
      characterized immune system and high degree of susceptibility to tuberculosis
      caused by Mycobacterium marinum. The D. melanogaster-M. marinum infection model
      is gaining momentum as a screening tool because it is genetically amenable, low
      priced, rapid, technically convenient and ethically acceptable. In this context,
      the aim of this study was to develop a new, effective D. melanogaster-M. marinum
      in vivo efficacy model for antimycobacterial drug discovery. METHODS: D.
      melanogaster were challenged with intra-abdominal injections of M. marinum and
      infected flies were fed with a fly medium containing isoniazid, rifampicin,
      ethambutol, pyrazinamide, amikacin, dinitrobenzamide or ampicillin dissolved in
      DMSO at different concentrations (0, 100 and 500 mg/L). Bacterial dissemination
      in flies was monitored by fluorescence microscopy/cfu counts and a fly survival
      curve was plotted. RESULTS: The D. melanogaster-M. marinum model allowed
      assessment of the effectiveness of antibiotic treatment not only with
      conventional drugs, but also with newly discovered antimycobacterial agents.
      Rifampicin, dinitrobenzamide, amikacin and isoniazid effectively extended the
      life span of infected flies and ethambutol showed slightly improved survival.
      However, M. marinum infection was not cured by ampicillin or pyrazinamide.
      CONCLUSIONS: This D. melanogaster-M. marinum infection/curing methodology may be
      valuable in the rapid evaluation of the activity of new antimycobacterial agents
      in drug discovery.

PMID- 23118146
TI  - Assessment of the effects of severe obesity and lifestyle risk factors on stage
      of endometrial cancer.
AB  - BACKGROUND: Lifestyle risk factors, including obesity, have been associated with
      increased risk of endometrial cancer (EC). Women with higher obesity levels tend
      to have less aggressive EC disease stage and histology. This study further
      investigated associations between nonmodifiable risk factors, such as age, race,
      and grade, and modifiable lifestyle factors, such as diet and physical activity
      expenditure, in relation to severe obesity and late versus early EC stage at
      diagnosis. METHODS: Demographic, anthropometric, and lifestyle surveys were
      administered to 177 women with histologically confirmed EC. Logistic regression
      analyses assessed the relationship between obesity and other risk factors on EC
      stage at diagnosis. RESULTS: In multivariate models, body mass index (BMI) < 35
      was not significantly associated with late EC stage at diagnosis (OR = 1.67, P =
      0.219) when adjusting for grade and age. Grade was significantly associated with
      EC stage when controlling for BMI and age (OR = 8.48, P = .000). Women more than
      the age of 60 had a fourfold increased risk of diagnosis at late versus early EC
      stage when adjusting for other risk factors. Age had a confounding effect on the
      obesity-EC stage association. CONCLUSIONS: Our results corroborate those of past
      studies showing that BMI is not an independent risk factor for EC stage and that
      age may have confounded the obesity-EC stage association. Because of mixed
      results and implications for treatment outcomes, however, further research
      examining these variables is warranted. IMPACT: Our results provide further
      insight into the obesity EC-stage association, especially the confounding effect
      of age. Future studies should examine modifiable lifestyle factors in larger and
      more diverse populations.

PMID- 23118148
TI  - Sialolithiasis in an HIV-1-infected patient treated with atazanavir/ritonavir
      monotherapy.

PMID- 23118150
TI  - Intestinal microbiota determine severity of myocardial infarction in rats.

PMID- 23118152
TI  - The scientist as world citizen.

PMID- 23118149
TI  - Validation of LC-TOF-MS screening for drugs, metabolites, and collateral
      compounds in forensic toxicology specimens.
AB  - Liquid chromatography time-of-flight mass spectrometry (LC-TOF-MS) analysis
      provides an expansive technique for identifying many known and unknown analytes.
      This study developed a screening method that utilizes automated solid-phase
      extraction to purify a wide array of analytes involving stimulants,
      benzodiazepines, opiates, muscle relaxants, hypnotics, antihistamines,
      antidepressants and newer synthetic "Spice/K2" cannabinoids and cathinone "bath
      salt" designer drugs. The extract was applied to LC-TOF-MS analysis, implementing
      a 13 min chromatography gradient with mobile phases of ammonium formate and
      methanol using positive mode electrospray. Several common drugs and metabolites
      can share the same mass and chemical formula among unrelated compounds, but they
      are structurally different. In this method, the LC-TOF-MS was able to resolve
      many isobaric compounds by accurate mass correlation within 15 ppm mass units and
      a narrow retention time interval of less than 10 s of separation. Drug recovery
      yields varied among spiked compounds, but resulted in overall robust area counts
      to deliver an average match score of 86 when compared to the retention time and
      mass of authentic standards. In summary, this method represents a rapid, enhanced
      screen for blood and urine specimens in postmortem, driving under the influence,
      and drug facilitated sexual assault forensic toxicology casework.

PMID- 23118157
TI  - Science and the law. Convictions leave Italy's civil protection in chaos.

PMID- 23118158
TI  - Stem cells. Immune reactions help reprogram cells.

PMID- 23118159
TI  - Paleontology. Flying dinos and baby birds offer new clues about how avians took
      wing.

PMID- 23118160
TI  - Education. Indonesia to drop science for youngest students.

PMID- 23118161
TI  - Genetics. Cancer gene data casts doubt on popular research method.

PMID- 23118162
TI  - Scientific meetings. U.S. agencies feel the pinch of travel cutbacks.

PMID- 23118163
TI  - Global research universities. Excellence, ja, elitism, non.

PMID- 23118164
TI  - Marine biology. Putting rockfish back where they belong.

PMID- 23118165
TI  - Antarctic Treaty System ready for a challenge.

PMID- 23118166
TI  - China's wastewater treatment goals.

PMID- 23118168
TI  - Comment on "Multiyear prediction of monthly mean Atlantic Meridional Overturning
      Circulation at 26.5 degrees N".
AB  - Matei et al. (Reports, 6 January 2012, p. 76) claim to show skillful multiyear
      predictions of the Atlantic Meridional Overturning Circulation (AMOC). However,
      these claims are not justified, primarily because the predictions of AMOC
      transport do not outperform simple reference forecasts based on climatological
      annual cycles. Accordingly, there is no justification for the "confident"
      prediction of a stable AMOC through 2014.

PMID- 23118170
TI  - Denuclearization's indirect consequences.

PMID- 23118171
TI  - Science and government. Obama and the promotion of international science.

PMID- 23118172
TI  - Public health. Optimizing investments in malaria treatment and diagnosis.

PMID- 23118173
TI  - Public health. From financing to fevers: lessons of an antimalarial subsidy
      program.

PMID- 23118174
TI  - Economics. Implications of scarcity.

PMID- 23118175
TI  - Evolution. Getting to the root of aging.

PMID- 23118176
TI  - Evolution. How cichlids diversify.

PMID- 23118177
TI  - Physics. Quantum procrastination.

PMID- 23118178
TI  - Plant science. Chloroplast delivery by UPS.

PMID- 23118179
TI  - Molecular biology. A new direction for gene loops.

PMID- 23118180
TI  - Materials science. Getting Moore from solar cells.

PMID- 23118181
TI  - Biochemistry. Templating a molecular tug-of-war.

PMID- 23118182
TI  - Marine microbes see a sea of gradients.
AB  - Marine bacteria influence Earth's environmental dynamics in fundamental ways by
      controlling the biogeochemistry and productivity of the oceans. These large-scale
      consequences result from the combined effect of countless interactions occurring
      at the level of the individual cells. At these small scales, the ocean is
      surprisingly heterogeneous, and microbes experience an environment of pervasive
      and dynamic chemical and physical gradients. Many species actively exploit this
      heterogeneity, while others rely on gradient-independent adaptations. This is an
      exciting time to explore this frontier of oceanography, but understanding
      microbial behavior and competition in the context of the water column's
      microarchitecture calls for new ecological frameworks, such as a microbial
      optimal foraging theory, to determine the relevant trade-offs and global
      consequences of microbial life in a sea of gradients.

PMID- 23118183
TI  - A quantum delayed-choice experiment.
AB  - Quantum systems exhibit particle- or wavelike behavior depending on the
      experimental apparatus they are confronted by. This wave-particle duality is at
      the heart of quantum mechanics. Its paradoxical nature is best captured in the
      delayed-choice thought experiment, in which a photon is forced to choose a
      behavior before the observer decides what to measure. Here, we report on a
      quantum delayed-choice experiment in which both particle and wave behaviors are
      investigated simultaneously. The genuinely quantum nature of the photon's
      behavior is certified via nonlocality, which here replaces the delayed choice of
      the observer in the original experiment. We observed strong nonlocal
      correlations, which show that the photon must simultaneously behave both as a
      particle and as a wave.

PMID- 23118184
TI  - Entanglement-enabled delayed-choice experiment.
AB  - Wave-particle complementarity is one of the most intriguing features of quantum
      physics. To emphasize this measurement apparatus-dependent nature, experiments
      have been performed in which the output beam splitter of a Mach-Zehnder
      interferometer is inserted or removed after a photon has already entered the
      device. A recent extension suggested using a quantum beam splitter at the
      interferometer's output; we achieve this using pairs of polarization-entangled
      photons. One photon is tested in the interferometer and is detected, whereas the
      other allows us to determine whether wave, particle, or intermediate behaviors
      have been observed. Furthermore, this experiment allows us to continuously morph
      the tested photon's behavior from wavelike to particle-like, which illustrates
      the inadequacy of a naive wave or particle description of light.

PMID- 23118185
TI  - Quantum entanglement of high angular momenta.
AB  - Single photons with helical phase structures may carry a quantized amount of
      orbital angular momentum (OAM), and their entanglement is important for quantum
      information science and fundamental tests of quantum theory. Because there is no
      theoretical upper limit on how many quanta of OAM a single photon can carry, it
      is possible to create entanglement between two particles with an arbitrarily high
      difference in quantum number. By transferring polarization entanglement to OAM
      with an interferometric scheme, we generate and verify entanglement between two
      photons differing by 600 in quantum number. The only restrictive factors toward
      higher numbers are current technical limitations. We also experimentally
      demonstrate that the entanglement of very high OAM can improve the sensitivity of
      angular resolution in remote sensing.

PMID- 23118186
TI  - Photoinduced Ullmann C-N coupling: demonstrating the viability of a radical
      pathway.
AB  - Carbon-nitrogen (C-N) bond-forming reactions of amines with aryl halides to
      generate arylamines (anilines), mediated by a stoichiometric copper reagent at
      elevated temperature (>180 degrees C), were first described by Ullmann in 1903.
      In the intervening century, this and related C-N bond-forming processes have
      emerged as powerful tools for organic synthesis. Here, we report that Ullmann C-N
      coupling can be photoinduced by using a stoichiometric or a catalytic amount of
      copper, which enables the reaction to proceed under unusually mild conditions
      (room temperature or even -40 degrees C). An array of data are consistent with a
      single-electron transfer mechanism, representing the most substantial
      experimental support to date for the viability of this pathway for Ullmann C-N
      couplings.

PMID- 23118187
TI  - The absolute chronology and thermal processing of solids in the solar
      protoplanetary disk.
AB  - Transient heating events that formed calcium-aluminum-rich inclusions (CAIs) and
      chondrules are fundamental processes in the evolution of the solar protoplanetary
      disk, but their chronology is not understood. Using U-corrected Pb-Pb dating, we
      determined absolute ages of individual CAIs and chondrules from primitive
      meteorites. CAIs define a brief formation interval corresponding to an age of
      4567.30 +/- 0.16 million years (My), whereas chondrule ages range from 4567.32 +/
      0.42 to 4564.71 +/- 0.30 My. These data refute the long-held view of an age gap
      between CAIs and chondrules and, instead, indicate that chondrule formation
      started contemporaneously with CAIs and lasted ~3 My. This time scale is similar
      to disk lifetimes inferred from astronomical observations, suggesting that the
      formation of CAIs and chondrules reflects a process intrinsically linked to the
      secular evolution of accretionary disks.

PMID- 23118188
TI  - Chloroplast biogenesis is regulated by direct action of the ubiquitin-proteasome
      system.
AB  - Development of chloroplasts and other plastids depends on the import of thousands
      of nucleus-encoded proteins from the cytosol. Import is initiated by TOC
      (translocon at the outer envelope of chloroplasts) complexes in the plastid outer
      membrane that incorporate multiple, client-specific receptors. Modulation of
      import is thought to control the plastid's proteome, developmental fate, and
      functions. Using forward genetics, we identified Arabidopsis SP1, which encodes a
      RING-type ubiquitin E3 ligase of the chloroplast outer membrane. The SP1 protein
      associated with TOC complexes and mediated ubiquitination of TOC components,
      promoting their degradation. Mutant sp1 plants performed developmental
      transitions that involve plastid proteome changes inefficiently, indicating a
      requirement for reorganization of the TOC machinery. Thus, the ubiquitin
      proteasome system acts on plastids to control their development.

PMID- 23118189
TI  - Synchronizing nuclear import of ribosomal proteins with ribosome assembly.
AB  - Ribosomal proteins are synthesized in the cytoplasm, before nuclear import and
      assembly with ribosomal RNA (rRNA). Little is known about coordination of
      nucleocytoplasmic transport with ribosome assembly. Here, we identify a transport
      adaptor, symportin 1 (Syo1), that facilitates synchronized coimport of the two 5S
      rRNA binding proteins Rpl5 and Rpl11. In vitro studies revealed that Syo1
      concomitantly binds Rpl5-Rpl11 and furthermore recruits the import receptor
      Kap104. The Syo1-Rpl5-Rpl11 import complex is released from Kap104 by RanGTP and
      can be directly transferred onto the 5S rRNA. Syo1 can shuttle back to the
      cytoplasm by interaction with phenylalanine-glycine nucleoporins. X-ray
      crystallography uncovered how the alpha-solenoid symportin accommodates the Rpl5
      amino terminus, normally bound to 5S rRNA, in an extended groove. Symportin
      mediated coimport of Rpl5-Rpl11 could ensure coordinated and stoichiometric
      incorporation of these proteins into pre-60S ribosomes.

PMID- 23118190
TI  - Trade-offs of chemotactic foraging in turbulent water.
AB  - Bacteria play an indispensable role in marine biogeochemistry by recycling
      dissolved organic matter. Motile species can exploit small, ephemeral solute
      patches through chemotaxis and thereby gain a fitness advantage over nonmotile
      competitors. This competition occurs in a turbulent environment, yet turbulence
      is generally considered inconsequential for bacterial uptake. In contrast, we
      show that turbulence affects uptake by stirring nutrient patches into networks of
      thin filaments that motile bacteria can readily exploit. We find that chemotactic
      motility is subject to a trade-off between the uptake benefit due to chemotaxis
      and the cost of locomotion, resulting in an optimal swimming speed. A second
      trade-off results from the competing effects of stirring and mixing and leads to
      the prediction that chemotaxis is optimally favored at intermediate turbulence
      intensities.

PMID- 23118192
TI  - Some consequences of having too little.
AB  - Poor individuals often engage in behaviors, such as excessive borrowing, that
      reinforce the conditions of poverty. Some explanations for these behaviors focus
      on personality traits of the poor. Others emphasize environmental factors such as
      housing or financial access. We instead consider how certain behaviors stem
      simply from having less. We suggest that scarcity changes how people allocate
      attention: It leads them to engage more deeply in some problems while neglecting
      others. Across several experiments, we show that scarcity leads to attentional
      shifts that can help to explain behaviors such as overborrowing. We discuss how
      this mechanism might also explain other puzzles of poverty.

PMID- 23118191
TI  - Asymmetric division of Drosophila male germline stem cell shows asymmetric
      histone distribution.
AB  - Stem cells can self-renew and generate differentiating daughter cells. It is not
      known whether these cells maintain their epigenetic information during asymmetric
      division. Using a dual-color method to differentially label "old" versus "new"
      histones in Drosophila male germline stem cells (GSCs), we show that preexisting
      canonical H3, but not variant H3.3, histones are selectively segregated to the
      GSC, whereas newly synthesized histones incorporated during DNA replication are
      enriched in the differentiating daughter cell. The asymmetric histone
      distribution occurs in GSCs but not in symmetrically dividing progenitor cells.
      Furthermore, if GSCs are genetically manipulated to divide symmetrically, this
      asymmetric mode is lost. This work suggests that stem cells retain preexisting
      canonical histones during asymmetric cell divisions, probably as a mechanism to
      maintain their unique molecular properties.

PMID- 23118193
TI  - Oxytocin's fingerprint in personality traits and regional brain volume.
AB  - Oxytocin has a fundamental role in social behavior. In humans, supporting
      evidence shows that oxytocin enhances people's ability to trust or affiliate with
      others. A key question is whether differences in plasma oxytocin concentration in
      humans are related to people's differences in their social traits of personality
      and if such differences are reflected in the structural organization of brain
      areas responsive to the action of this hormone. We examined the correlation
      between oxytocin plasma levels and personality traits in 30 healthy subjects,
      tested with the Inventory revised neuroticism-extroversion-openness personality
      inventory (NEO-PI-R). By using the voxel-based morphometry technique, we also
      investigated changes in gray matter volume as a function of the plasma oxytocin
      level and NEO-PI-R scores. A positive correlation was found between plasma
      oxytocin and extraversion scores, a dimension that captures social affiliative
      tendencies. Moreover, we found an inverse correlation between plasma oxytocin and
      the volume of the right amygdala and the right hippocampus, 2 brain areas
      implicated in fear and anxiety. Finally, we showed that the amygdala-hippocampal
      complex correlate negatively with extraversion scores. Our findings provide
      evidence for a neural mechanism linking physiological oxytocin's variability and
      structural variation of brain regions relevant for emotion regulation to
      individual differences in affiliative personality traits.

PMID- 23118194
TI  - Cross-modal plasticity preserves functional specialization in posterior parietal
      cortex.
AB  - In congenitally blind individuals, many regions of the brain that are typically
      heavily involved in visual processing are recruited for a variety of nonvisual
      sensory and cognitive tasks (Rauschecker 1995; Pascual-Leone et al. 2005). This
      phenomenon-cross-modal plasticity-has been widely documented, but the principles
      that determine where and how cross-modal changes occur remain poorly understood
      (Bavelier and Neville 2002). Here, we evaluate the hypothesis that cross-modal
      plasticity respects the type of computations performed by a region, even as it
      changes the modality of the inputs over which they are carried out (Pascual-Leone
      and Hamilton 2001). We compared the fMRI signal in sighted and congenitally blind
      participants during proprioceptively guided reaching. We show that
      parietooccipital reach-related regions retain their functional role-encoding of
      the spatial position of the reach target-even as the dominant modality in this
      region changes from visual to nonvisual inputs. This suggests that the
      computational role of a region, independently of the processing modality,
      codetermines its potential cross-modal recruitment. Our findings demonstrate that
      preservation of functional properties can serve as a guiding principle for cross
      modal plasticity even in visuomotor cortical regions, i.e. beyond the early
      visual cortex and other traditional visual areas.

PMID- 23118195
TI  - Fate mapping by piggyBac transposase reveals that neocortical GLAST+ progenitors
      generate more astrocytes than Nestin+ progenitors in rat neocortex.
AB  - Progenitors within the neocortical ventricular zone (VZ) first generate pyramidal
      neurons and then astrocytes. We applied novel piggyBac transposase lineage
      tracking methods to fate-map progenitor populations positive for Nestin or
      glutamate and aspartate transpoter (GLAST) promoter activities in the rat
      neocortex. GLAST+ and Nestin+ progenitors at embryonic day 13 (E13) produce
      lineages containing similar rations of neurons and astrocytes. By E15, the GLAST+
      progenitor population diverges significantly to produce lineages with 5-10-fold
      more astrocytes relative to neurons than generated by the Nestin+ population. To
      determine when birth-dated progeny within GLAST+ and Nestin+ populations diverge,
      we used a Cre/loxP fate-mapping system in which plasmids are lost after a cell
      division. By E18, birth-dated progeny of GLAST+ progenitors give rise to 2-3-fold
      more neocortical astrocytes than do Nestin+ progenitors. Finally, we used a
      multicolor clonal labeling method to show that the GLAST+ population labeled at
      E15 generates astrocyte progenitors that produce larger, spatially restricted,
      clonal clusters than the Nestin+ population. This study provides in vivo evidence
      that by mid-corticogenesis (E15), VZ progenitor populations have significantly
      diversified in terms of their potential to generate astrocytes and neurons.

PMID- 23118196
TI  - Pansynaptic enlargement at adult cortical connections strengthened by experience.
AB  - Behavioral experience alters the strength of neuronal connections in adult
      neocortex. These changes in synaptic strength are thought to be central to
      experience-dependent plasticity, learning, and memory. However, it is not known
      how changes in synaptic transmission between neurons become persistent, thereby
      enabling the storage of previous experience. A long-standing hypothesis is that
      altered synaptic strength is maintained by structural modifications to synapses.
      However, the extent of synaptic modifications and the changes in
      neurotransmission that the modifications support remain unclear. To address these
      questions, we recorded from pairs of synaptically connected layer 2/3 pyramidal
      neurons in the barrel cortex and imaged their contacts with high-resolution
      confocal microscopy after altering sensory experience by whisker trimming.
      Excitatory connections strengthened by experience exhibited larger axonal
      varicosities, dendritic spines, and interposed contact zones. Electron microscopy
      showed that contact zone size was strongly correlated with postsynaptic density
      area. Therefore, our findings indicate that whole synapses are larger at
      strengthened connections. Synaptic transmission was both stronger and more
      reliable following experience-dependent synapse enlargement. Hence, sensory
      experience modified both presynaptic and postsynaptic function. Our findings
      suggest that the enlargement of synaptic contacts is an integral part of long
      lasting strengthening of cortical connections and, hence, of information storage
      in the neocortex.

PMID- 23118197
TI  - Dissociated alpha-band modulations in the dorsal and ventral visual pathways in
      visuospatial attention and perception.
AB  - Modulations of occipito-parietal alpha-band (8-14 Hz) power that are opposite in
      direction (alpha-enhancement vs. alpha-suppression) and origin of generation
      (ipsilateral vs. contralateral to the locus of attention) are a robust correlate
      of anticipatory visuospatial attention. Yet, the neural generators of these alpha
      band modulations, their interdependence across homotopic areas, and their
      respective contribution to subsequent perception remain unclear. To shed light on
      these questions, we employed magnetoencephalography, while human volunteers
      performed a spatially cued detection task. Replicating previous findings, we
      found alpha-power enhancement ipsilateral to the attended hemifield and
      contralateral alpha-suppression over occipito-parietal sensors. Source
      localization (beamforming) analysis showed that alpha-enhancement and suppression
      were generated in 2 distinct brain regions, located in the dorsal and ventral
      visual streams, respectively. Moreover, alpha-enhancement and suppression showed
      different dynamics and contribution to perception. In contrast to the initial and
      transient dorsal alpha-enhancement, alpha-suppression in ventro-lateral occipital
      cortex was sustained and influenced subsequent target detection. This
      anticipatory biasing of ventro-lateral extrastriate alpha-activity probably
      reflects increased receptivity in the brain region specialized in processing
      upcoming target features. Our results add to current models on the role of alpha
      oscillations in attention orienting by showing that alpha-enhancement and
      suppression can be dissociated in time, space, and perceptual relevance.

PMID- 23118199
TI  - Multisensory parietal cortex contributes to visual enhancement of touch in
      humans: A single-pulse TMS study.
AB  - We used transcranial magnetic stimulation (TMS) to investigate how the visual
      context provided by viewing one's own body influences somatosensory processing.
      In the visual enhancement of touch (VET) effect, viewing the body enhances
      tactile acuity relative to viewing a nonbody object. Single-pulse TMS was
      delivered over anterior intraparietal sulcus (aIPS), which is crucial for
      integrating visual and somatosensory information related to the body, during the
      interval between a brief glimpse of the arm, or an object, and tactile
      stimulation. TMS to aIPS just after visual stimulation abolished VET, while TMS
      at the time of touch itself did not. Disrupting nearby areas just anterior or
      posterior to aIPS left the VET effect intact. Viewing the arm may activate
      multisensory areas in aIPS, which may then rapidly modulate somatosensory
      circuits. We suggest that this enhancement of touch by vision involves feedback
      signals from aIPS to unimodal somatosensory cortex. Our study provides causal
      evidence of a specific multisensory mechanism that modulates tactile processing
      in the human brain.

PMID- 23118200
TI  - Is labetalol really a culprit in neonatal hypoglycaemia?

PMID- 23118198
TI  - Anatomic and molecular development of corticostriatal projection neurons in mice.
AB  - Corticostriatal projection neurons (CStrPN) project from the neocortex to
      ipsilateral and contralateral striata to control and coordinate motor programs
      and movement. They are clinically important as the predominant cortical
      population that degenerates in Huntington's disease and corticobasal ganglionic
      degeneration, and their injury contributes to multiple forms of cerebral palsy.
      Together with their well-studied functions in motor control, these clinical
      connections make them a functionally, behaviorally, and clinically important
      population of neocortical neurons. Little is known about their development.
      "Intratelencephalic" CStrPN (CStrPNi), projecting to the contralateral striatum,
      with their axons fully within the telencephalon (intratelencephalic), are a major
      population of CStrPN. CStrPNi are of particular interest developmentally because
      they share hodological and axon guidance characteristics of both callosal
      projection neurons (CPN) and corticofugal projection neurons (CFuPN); CStrPNi
      send axons contralaterally before descending into the contralateral striatum. The
      relationship of CStrPNi development to that of broader CPN and CFuPN populations
      remains unclear; evidence suggests that CStrPNi might be evolutionary "hybrids"
      between CFuPN and deep layer CPN-in a sense "chimeric" with both callosal and
      corticofugal features. Here, we investigated the development of CStrPNi in mice
      their birth, maturation, projections, and expression of molecular developmental
      controls over projection neuron subtype identity.

PMID- 23118201
TI  - Clock drawing test in elderly individuals with different education levels:
      correlation with clinical dementia rating.
AB  - OBJECTIVE: The aim of this study was to describe the performance in Clock Drawing
      Test (CDT) of the elderly individuals assessed in a geriatric clinic, with at
      least 1 year of schooling, comparing with other groups with higher education and
      with Clinical Dementia Rating (CDR) levels. The study also aims to correlate the
      results of CDT and other used diagnostic tests for dementia by CDR levels,
      providing additional validity evidence to the CDT. METHODS: Cross-sectional study
      with 426 elderly individuals, >60 years old and at least 1 year of education. All
      participants searched for medical assistance at Geriatric and Gerontology
      Ambulatory of Jundiai city, in Brazil. The community-dwelling outpatients
      previously undergone a detailed clinical examination and neuropsychological
      evaluation: Cambrigde Cognitive Examination (CAMCOG), Mini-Mental State
      Examination (MMSE), andCDT. To differentiate data from diagnostic groups based on
      CDR, it Kruskal-Wallis test was used. Pearson statistics were calculated to
      compare data from CDT and CDR. The statistical analyses were 2-tailed and were
      considered significant when P < .05. RESULTS: Regarding CDT, groups with more
      years of schooling showed similar means in CDR = 0 and CDR = 0.5 and in CDR = 1
      and CDR = 2. Shulman and Sunderland scale were high score in groups with more
      years of education and above of cutoff points in all CDT score. On the contrary,
      in Mendez scale we did not observed similar means. Otherwise, in the group with
      less years of schooling greater means differences in the CDT were observed.
      CONCLUSION: The CDT did not show a strong correlation with MMSE and CAMCOG, both
      important instruments in Brazilian population to investigate dementia. For
      elderly individuals with high education levels, the CDT did not seem to be a good
      test to detect cognitive impairment.

PMID- 23118202
TI  - Identifying hospital organizational strategies to reduce readmissions.
AB  - With looming financial penalties for institutions with high readmission rates,
      hospital administrators are under pressure to implement strategies to reduce
      readmissions despite limited evidence of effective strategies. The objectives of
      this study were to understand the process of developing readmission reduction
      strategies and to identify and categorize the range of strategies being
      implemented. The authors designed a qualitative study using semistructured
      interviews with 12 hospital administrators at 6 different hospitals. The
      following 6 categories of strategies were identified: (a) tracking readmissions,
      (b) using prediction tools, (c) implementing disease-specific or generic
      readmission reduction programs, (d) adopting electronic health record-based
      strategies to improve transitions, (e) recruiting frontline staff for program
      leadership, and (f) coordinating with primary care providers. The results
      highlight the myriad approaches to readmission reduction and the complexity of
      developing effective strategies. 

PMID- 23118203
TI  - Smelling shapes: crossmodal correspondences between odors and shapes.
AB  - Crossmodal correspondences between odors and visual stimuli-particularly colors
      are well-established in the literature, but there is a paucity of research
      involving visual shape correspondences. Crossmodal associations between 20 odors
      (a selection of those commonly found in wine) and visual shape stimuli
      ("kiki"/"bouba" forms-Kohler W. 1929. Gestalt psychology. New York: Liveright.)
      were investigated in a sample of 25 participants (mean age of 21 years). The
      odors were rated along a form scale anchored by 2 shapes, as well as several
      descriptive adjective scales. Two of the odors were found to be significantly
      associated with an angular shape (lemon and pepper) and two others with a rounded
      shape (raspberry and vanilla). Principal component analysis indicated that the
      hedonic value and intensity of odors are important in this crossmodal
      association, with more unpleasant and intense smells associated with more angular
      forms. These results are discussed in terms of their practical applications, such
      as in the use of bottle, logo, or label shape by marketers of perfume and wine to
      convey the prominent notes through congruent odor-shape pairing. In conclusion,
      these results support the existence of widespread crossmodal associations (or
      correspondences) between odors and visual shape stimuli.

PMID- 23118204
TI  - Genetic variation in putative salt taste receptors and salt taste perception in
      humans.
AB  - The objective of this study was to determine whether single nucleotide
      polymorphisms (SNPs) in the SCNN1A (3), SCNN1B (12), SCNN1G (6), and TRPV1 (10)
      genes affect salt taste perception. Participants were men (n = 28) and women (n =
      67) from the Toronto Nutrigenomics and Health study aged 21-31 years. Taste
      thresholds were determined using a 3-alternative forced-choice staircase model
      with solutions ranging from 9*10(-6) to 0.5 mol/L. Suprathreshold taste
      sensitivity to 0.01-1.0 mol/L salt solutions was assessed using general labeled
      magnitude scales. None of the SNPs in the SCNN1A and SCNN1G genes were
      significantly associated with either outcome. In the SCNN1B gene, 2 SNPs in
      intronic regions of the gene modified suprathreshold taste sensitivity (mean iAUC
      +/- SE). Those homozygous for the A allele of the rs239345 (A>T) polymorphism and
      the T allele of the rs3785368 (C>T) polymorphism perceived salt solutions less
      intensely than carriers of the T or C alleles, respectively (rs239345: 70.82+/
      12.16 vs. 96.95+/-3.75, P = 0.02; rs3785368: 57.43+/-19.85 vs. 95.57+/-3.66, P =
      0.03) In the TRPV1 gene, the rs8065080 (C>T, Val585Ile) polymorphism modified
      suprathreshold taste sensitivity where carriers of the T allele were
      significantly more sensitive to salt solutions than the CC genotype (98.3+/-3.8
      vs. 74.1+/-8.3, P = 0.008). Our findings show that variation in the TRPV1 and the
      SCNN1B genes may modify salt taste perception in humans.

PMID- 23118205
TI  - Mind over age--stereotype activation and olfactory function.
AB  - Given that context affects olfaction and the elderly exhibit olfactory deficits,
      the current study tested whether a subtle change in internal context, evoked by
      priming the elderly stereotype, would affect performance in a variety of
      olfactory tasks including odor sensitivity, discrimination, and identification
      (Experiment 1), as well as perceived odor intensity, pleasantness and
      familiarity, and an odor reaction time task (Experiment 2). Such internalization
      of the elderly stereotype has been demonstrated with slower walking speeds and
      fewer words recalled in a memory task. In the current study, 76 participants
      first listened to a presentation about age-related declines in olfaction and then
      participated in 3 language tasks which, unbeknownst to them, served as the
      elderly stereotype priming manipulation. This priming manipulation was effective
      at decreasing walking speed and word recall, confirming the findings of previous
      researchers; however, olfaction was not affected. Whether olfaction is resistant
      to stereotype priming is discussed.

PMID- 23118206
TI  - Affinities of recombinant norovirus P dimers for human blood group antigens.
AB  - Noroviruses (NoVs), the major cause of viral acute gastroenteritis, recognize
      histo-blood group antigens (HBGAs) as receptors or attachment factors. To gain a
      deeper understanding of the interplay between NoVs and their hosts, the
      affinities of recombinant P dimers (P2's) of a GII.4 NoV (VA387) to a library of
      41 soluble analogs of HBGAs were measured using the direct electrospray
      ionization mass spectrometry assay. The HBGAs contained the A, B, H and Lewis
      epitopes, with variable sizes (2-6 residues) and different types (1-6). The
      results reveal that the P2's exhibit a broad specificity for the HBGAs and bind
      to all of the oligosaccharides tested. Overall, the affinities are relatively
      low, ranging from 400 to 3000 M-1 and are influenced by the chain type: 3 > 1 ~ 2
      ~ 4 ~ 5 ~ 6 for H antigens; 6 > 1 ~ 3 ~ 4 ~ 5 > 2 for A antigens; 3 > 1 ~ 4 ~ 5 ~
      6 > 2 for B antigens, but not by chain length. The highest-affinity ligands are B
      type 3 (3000 +/- 300 M-1) and A type 6 (2350 +/- 60 M-1). While the higher
      affinity to the type 3 H antigen was previously observed, preferential binding to
      the types 6 and 3 antigens with A and B epitopes, respectively, has not been
      previously reported. A truncated P domain dimer (lacking the C-terminal arginine
      cluster) exhibits similar binding. The central-binding motifs in the HBGAs were
      identified by molecular-docking simulations.

PMID- 23118207
TI  - Structure and biosynthetic locus of the lipopolysaccharide outer core produced by
      Pasteurella multocida serovars 8 and 13 and the identification of a novel phospho
      glycero moiety.
AB  - Pasteurella multocida strains are classified into 16 Heddleston serovars on the
      basis of the lipopolysaccharide (LPS) antigens expressed on the surface of the
      bacteria. The LPS structure and the corresponding LPS outer core biosynthesis
      loci of strains belonging to serovars 1, 2, 3, 5, 9 and 14 have been
      characterized, revealing a clear structural basis for serovar classification.
      However, several of these serovars are genetically related, sharing the same LPS
      outer core biosynthesis locus, but producing different LPS molecules as a result
      of mutations within LPS assembly genes. In this article, we report that the P.
      multocida type strains belonging to serovars 8 and 13 share the same LPS outer
      core biosynthesis locus and produce structurally related LPS molecules.
      Structural analysis of the serovar 8 LPS revealed an inner core that is conserved
      among P. multocida strains and the following outer core structure: X-(1-6)
      (1S)GalaNAC-(1-4-6)-alpha-Gal-(1-3)-beta-Gal(PEtn)-(1-4)-L,D-alpha-Hep-(1-6)
      where X is a unique phospho-glycero moiety, 1-((4-aminobutyl)amino)-3-hydroxy-1
      oxopropan-2-yl hydrogen phosphate, attached to the sixth position of (1S)GalaNAc.
      For serovar 13, the LPS structure is the same except for the absence of the
      terminal phospho-glycero moiety. Analysis of the common outer core biosynthesis
      locus from the serovar 8 and 13 type strains identified three genes that we
      predict are involved in the biosynthesis of this terminal moiety. Furthermore,
      bioinformatic comparisons with the characterized LPS outer core
      glycosyltransferases from Actinobacillus pleuropneumoniae serovar 1, strain 4074,
      allowed us to assign a function for each of the glycosyltransferases encoded
      within the serovar 8/13 LPS outer core biosynthesis locus.

PMID- 23118209
TI  - Determination of nimodipine in the presence of its degradation products and
      overall kinetics through a stability-indicating LC method.
AB  - The determination of nimodipine in the presence of its degradation products,
      formed through photolysis, acidic and alkaline hydrolysis, and the drug
      degradation kinetics under these conditions, was investigated through a validated
      liquid chromatography method. Separation was achieved using a Phenomenex Luna C18
      column (250 * 4.6 mm i.d., 5 um) with a mobile phase consisting of acetonitrile
      methanol-water (55:11:34, v/v/v), at 0.5 mL/min and with ultraviolet detection at
      235 nm. The method was considered to be specific, accurate, precise, robust and
      linear over the concentration range of 5.0 to 35.0 ug/mL. The drug followed a
      first-order reaction for both hydrolysis and photolysis in methanol, and zero
      order for photolysis in acetonitrile and water. The calculated activation
      energies were 10.899 and 23.442 kcal/mol for alkaline and acidic hydrolysis,
      respectively. No degradation was observed under thermal and oxidative stress
      conditions.

PMID- 23118208
TI  - A phenotype survey of 36 mutant mouse strains with gene-targeted defects in
      glycosyltransferases or glycan-binding proteins.
AB  - The consortium for functional glycomics (CFG) was a large research initiative
      providing networking and resources for investigators studying the role of glycans
      and glycan-binding proteins in health and disease. Starting in 2001, six
      scientific cores were established to generate data, materials and new
      technologies. By the end of funding in 2011, the mouse phenotype core (MPC)
      submitted data to a website from the phenotype screen of 36 mutant mouse strains
      deficient in a gene for either a glycan-binding protein (GBP) or
      glycosyltransferase (GT). Each mutant strain was allotted three months for
      analysis and screened by standard phenotype assays used in the fields of
      immunology, histology, hematology, coagulation, serum chemistry, metabolism and
      behavior. Twenty of the deficient mouse strains had been studied in other
      laboratories, and additional tests were performed on these strains to confirm
      previous observations and discover new data. The CFG constructed 16 new
      homozygous mutant mouse strains and completed the initial phenotype screen of the
      majority of these new mutant strains. In total, >300 phenotype changes were
      observed, but considering the over 100 assays performed on each strain, most of
      the phenotypes were unchanged. Phenotype differences include abnormal testis
      morphology in GlcNAcT9- and Siglec-H-deficient mice and lethality in Pomgnt1
      deficient mice. The numerous altered phenotypes discovered, along with the
      consideration of the significant findings of normality, will provide a platform
      for future characterization to understand the important roles of glycans and GBPs
      in the mechanisms of health and disease.

PMID- 23118210
TI  - Study on spectrum-effect relationship of rhizoma Rhei, cortex Magnoliae
      Officinalis, fructus Aurantii Immaturus and their formula.
AB  - Rhizoma Rhei, cortex Magnoliae Officinalis and fructus Aurantii Immaturus compose
      dachengqi tang (DCQT), a classical formula of traditional Chinese medicine (TCM)
      that is used for acute intestinal obstruction and has been proven to be effective
      and economic. However, the ingredients of TCM are complicated, and it is unclear
      which ingredients are the most important for its effects. In this paper, the
      relationship between the spectra and effects is discussed to provide a powerful
      method and some insights into the quality control of the herbs and their formula.
      High-performance liquid chromatographic (HPLC) fingerprint analysis was performed
      to investigate the chemical structures in different batches of rhizoma Rhei,
      cortex Magnoliae Officinalis, fructus Aurantii Immaturus and DCQT. Hierarchical
      clustering analysis was employed to evaluate the similarities between
      fingerprints. Animal model of small intestinal propulsion was established to
      study the purgative functions of the herbs and DCQT. The relationship between the
      chemical ingredients and the effects was explored by regression analysis. HPLC
      fingerprint analysis results demonstrated variations between ingredients in
      different batches of rhizoma Rhei, cortex Magnoliae Officinalis, fructus Aurantii
      Immaturus and DCQT. The origin, collection time and preparation process may have
      contributed to these differences. Small intestinal propulsion results showed
      that, compared with the control group, the positive and therapeutic groups
      including single herbs and formula were significantly effective (P < 0.05).
      Spectrum-effect relationship results indicated that seven peak ingredients,
      hesperidin, aloe-emodin, honokiol, rhein, magnolol, emodin and sennoside A, were
      inducted in the regression equation, among which, the influence of sennoside A
      was the largest and most positively associated with the effects. The data
      analysis results indicated that many ingredients contributed to the purgative
      effects, among which, sennoside A might be the most important effective
      component; therefore, sennoside A should be determined for quality control.
      Furthermore, the spectrum-effect relationship is simple, operative and suitable
      for the quality evaluation of TCM.

PMID- 23118211
TI  - Are 25 antibodies better than 1?

PMID- 23118212
TI  - Gene therapy for ADA-SCID: defining the factors for successful outcome.

PMID- 23118213
TI  - Transcription factor dose links development to disease.

PMID- 23118214
TI  - Helicobacter pylori eradication as exclusive treatment for limited-stage gastric
      diffuse large B-cell lymphoma: results of a multicenter phase 2 trial.

PMID- 23118215
TI  - Screening of novel genetic aberrations in pediatric acute myeloid leukemia: a
      report from the AIEOP AML-2002 study group.

PMID- 23118216
TI  - P-selectin glycoprotein ligand-1 inhibition blocks increased leukocyte
      endothelial interactions associated with sickle cell disease in mice.

PMID- 23118217
TI  - The triumph of good over evil: protection by the sickle gene against malaria.
AB  - The mechanisms underlying Plasmodium falciparum resistance in persons with sickle
      trait have been under active investigation for more than a half century. This
      Perspective reviews progress in solving this challenging problem, including
      recent studies that have exploited the genomics and proteomics of the parasite.
      The formation of Hb S polymer in the parasitized AS RBC leads to impaired
      parasite growth and development along with enhanced clearance from the
      circulation and reduced deposition in deep postcapillary vascular beds. Enhanced
      generation of reactive oxygen species in sickled AS RBCs is a pathogenetic
      feature shared by parasitized thalassemic and G6PD-deficient RBCs, triggering
      abnormal topology of the RBC plasma membrane with decreased and disordered
      display of PfEMP-1, a P falciparum adhesion protein critical for endothelial
      adherence. A mouse model of Hb S confers host tolerance to P berghei, through
      inhibition of pathogenic CD8(+) T cells and induction of heme oxygenase-1. An
      additional and apparently independent mode of protection is provided by the
      selective expression in AS RBCs of 2 species of microRNA that integrate into P
      falciparum mRNAs and inhibit translation and parasite growth.

PMID- 23118218
TI  - Delayed development of chronic lymphocytic leukemia in the absence of macrophage
      migration inhibitory factor.
AB  - Survival of chronic lymphocytic leukemia (CLL) cells depends on stimuli provided
      by a suitable microenvironment. The factors and mechanisms providing this growth
      support for CLL cells are not fully understood. We found that plasma levels of
      macrophage migration inhibitory factor (MIF), a proinflammatory and
      immunoregulatory chemokine, were elevated in CLL patients. Therefore, we
      characterized the functional role of MIF in a CLL mouse model. For this purpose,
      we crossed EMU-TCL1 mice with MIF knockout (MIF-/-) mice. The resulting
      TCL1+/wtMIF/ mice showed a delayed onset of leukemia, reduced splenomegaly and
      hepatomegaly, and a longer survival than TCL1+/wtMIFwt/wt controls.
      Immunohistochemical examination of the lymphoid organs showed that the numbers of
      macrophages were significantly reduced in the spleen and bone marrow of
      TCL1+/wtMIF/ mice compared with TCL1+/wtMIFwt/wt controls. Mechanistic studies in
      vitro revealed that the absence of MIF rendered CLL cells more susceptible to
      apoptosis. Accordingly, incubation with an anti-MIF antibody reduced the survival
      of CLL cells on a macrophage feeder layer. In addition, the migratory activity of
      TCL1+/wtMIF/ macrophages was decreased compared with TCL1+/wtMIFwt/wt
      macrophages. Taken together, our results provide evidence that MIF supports the
      development of CLL by enhancing the interaction of CLL cells with macrophages.
      KEY POINTS: Targeted deletion of the gene for macrophage migration inhibitory
      factor (MIF) delays development of chronic lymphocytic leukemia and prolongs
      survival in mice. MIF recruits leukemia-associated macrophages to spleen or
      liver.

PMID- 23118219
TI  - The high and low molecular weight forms of hyaluronan have distinct effects on
      CD44 clustering.
AB  - CD44 is a major cell surface receptor for the glycosaminoglycan hyaluronan (HA).
      Native high molecular weight hyaluronan (nHA) and oligosaccharides of hyaluronan
      (oHA) provoke distinct biological effects upon binding to CD44. Despite the
      importance of such interactions, however, the feature of binding with CD44 at the
      cell surface and the molecular basis for functional distinction between different
      sizes of HA is still unclear. In this study we investigated the effects of high
      and low molecular weight hyaluronan on CD44 clustering. For the first time, we
      provided direct evidence for a strong relationship between HA size and CD44
      clustering in vivo. In CD44-transfected COS-7 cells, we showed that exogenous nHA
      stimulated CD44 clustering, which was disrupted by oHA. Moreover, naturally
      expressed CD44 was distributed into clusters due to abundantly expressed nHA in
      HK-2 cells (human renal proximal tubule cells) and BT549 cells (human breast
      cancer cell line) without exogenous stimulation. Our results suggest that native
      HA binding to CD44 selectively induces CD44 clustering, which could be inhibited
      by oHA. Finally, we demonstrated that HA regulates cell adhesion in a manner
      specifically dependent on its size. oHA promoted cell adhesion while nHA showed
      no effects. Our results might elucidate a molecular- and/or cellular-based
      mechanism for the diverse biological activities of nHA and oHA.

PMID- 23118220
TI  - RSK2 protein suppresses integrin activation and fibronectin matrix assembly and
      promotes cell migration.
AB  - Modulation of integrin activation is important in many cellular functions
      including adhesion, migration, and assembly of the extracellular matrix. RSK2
      functions downstream of Ras/Raf and promotes tumor cell motility and metastasis.
      We therefore investigated whether RSK2 affects integrin function. We report that
      RSK2 mediates Ras/Raf inactivation of integrins. As a result, we find that RSK2
      impairs cell adhesion and integrin-mediated matrix assembly and promotes cell
      motility. Active RSK2 appears to affect integrins by reducing actin stress fibers
      and disrupting focal adhesions. Moreover, RSK2 co-localizes with the integrin
      activator talin and is present at integrin cytoplasmic tails. It is thereby in a
      position to modulate integrin activation and integrin-mediated migration.
      Activation of RSK2 promotes filamin phosphorylation and binding to integrins. We
      also find that RSK2 is activated in response to integrin ligation to fibronectin.
      Thus, RSK2 could participate in a feedback loop controlling integrin function.
      These results reveal RSK2 as a key regulator of integrin activity and provide a
      novel mechanism by which it may promote cell migration and cancer metastasis.

PMID- 23118221
TI  - Epigenetic regulation of galectin-3 expression by beta1 integrins promotes cell
      adhesion and migration.
AB  - Introduction of the integrin beta1- but not the beta3-subunit in GE11 cells
      induces an epithelial-to-mesenchymal-transition (EMT)-like phenomenon that is
      characterized by the loss of cell-cell contacts, cell scattering, increased cell
      migration and RhoA activity, and fibronectin fibrillogenesis. Because galactose
      binding lectins (galectins) have been implicated in these phenomena, we
      investigated whether galectins are involved in the beta1-induced phenotype. We
      examined 9 galectins and, intriguingly, found that the expression of galectin-3
      (Gal-3) is specifically induced by beta1 but not by beta3. Using beta1-beta3
      chimeric integrins, we show that the induction of Gal-3 expression requires the
      hypervariable region in the extracellular domain of beta1, but not its
      cytoplasmic tail. Furthermore, Gal-3 expression does not depend on RhoA
      signaling, serum factors, or any of the major signal transduction pathways
      involving protein kinase C (PKC), p38 mitogen-activated protein kinase (p38MAPK),
      extracellular signal-regulated kinase-1/-2 (ERK-1/2), phosphatidylinositol-3-OH
      kinase (PI3-K), or Src kinases. Instead, Gal-3 expression is controlled in an
      epigenetic manner. Whereas DNA methylation of the Lgals3 promoter maintains Gal-3
      silencing in GE11 cells, expression of beta1 causes its demethylation, leading to
      transcriptional activation of the Lgals3 gene. In turn, Gal-3 expression enhances
      beta1 integrin-mediated cell adhesion to fibronectin (FN) and laminin (LN), as
      well as cell migration. Gal-3 also promotes beta1-mediated cell adhesion to LN
      and Collagen-1 (Col)-1 in cells that endogenously express Gal-3 and beta1
      integrins. In conclusion, we identify a functional feedback-loop between beta1
      integrins and Gal-3 that involves the epigenetic induction of Gal-3 expression
      during integrin-induced EMT and cell scattering.

PMID- 23118222
TI  - An emerging role of Sonic hedgehog shedding as a modulator of heparan sulfate
      interactions.
AB  - Major developmental morphogens of the Hedgehog (Hh) family act at short range and
      long range to direct cell fate decisions in vertebrate and invertebrate tissues.
      To this end, Hhs are released from local sources and act at a distance on target
      cells that express the Hh receptor Patched. However, morphogen secretion and
      spreading are not passive processes because all Hhs are synthesized as dually (N-
      and C-terminal) lipidated proteins that firmly tether to the surface of producing
      cells. On the cell surface, Hhs associate with each other and with heparan
      sulfate (HS) proteoglycans. This raises the question of how Hh solubilization and
      spreading is achieved. We recently discovered that Sonic hedgehog (Shh) is
      solubilized by proteolytic processing (shedding) of lipidated peptide termini in
      vitro. Because unprocessed N termini block Patched receptor binding sites in the
      cluster, we further suggested that their proteolytic removal is required for
      simultaneous Shh activation. In this work we confirm inactivity of unprocessed
      protein clusters and demonstrate restored biological Shh function upon distortion
      or removal of N-terminal amino acids and peptides. We further show that N
      terminal Shh processing targets and inactivates the HS binding Cardin-Weintraub
      (CW) motif, resulting in soluble Shh clusters with their HS binding capacities
      strongly reduced. This may explain the ability of Shh to diffuse through the HS
      containing extracellular matrix, whereas other HS-binding proteins are quickly
      immobilized. Our in vitro findings are supported by the presence of CW-processed
      Shh in murine brain samples, providing the first in vivo evidence for Shh
      shedding and subsequent solubilization of N-terminal-truncated proteins.

PMID- 23118223
TI  - Dissecting and reconstructing synergism: in situ visualization of cooperativity
      among cellulases.
AB  - Cellulose is the most abundant biopolymer and a major reservoir of fixed carbon
      on earth. Comprehension of the elusive mechanism of its enzymatic degradation
      represents a fundamental problem at the interface of biology, biotechnology, and
      materials science. The interdependence of cellulose disintegration and hydrolysis
      and the synergistic interplay among cellulases is yet poorly understood. Here we
      report evidence from in situ atomic force microscopy (AFM) that delineates
      degradation of a polymorphic cellulose substrate as a dynamic cycle of
      alternating exposure and removal of crystalline fibers. Direct observation shows
      that chain-end-cleaving cellobiohydrolases (CBH I, CBH II) and an internally
      chain-cleaving endoglucanase (EG), the major components of cellulase systems,
      take on distinct roles: EG and CBH II make the cellulose surface accessible for
      CBH I by removing amorphous-unordered substrate areas, thus exposing otherwise
      embedded crystalline-ordered nanofibrils of the cellulose. Subsequently, these
      fibrils are degraded efficiently by CBH I, thereby uncovering new amorphous
      areas. Without prior action of EG and CBH II, CBH I was poorly active on the
      cellulosic substrate. This leads to the conclusion that synergism among
      cellulases is morphology-dependent and governed by the cooperativity between
      enzymes degrading amorphous regions and those targeting primarily crystalline
      regions. The surface-disrupting activity of cellulases therefore strongly depends
      on mesoscopic structural features of the substrate: size and packing of
      crystalline fibers are key determinants of the overall efficiency of cellulose
      degradation.

PMID- 23118224
TI  - Alcohol-induced one-carbon metabolism impairment promotes dysfunction of DNA base
      excision repair in adult brain.
AB  - The brain is one of the major targets of chronic alcohol abuse. Yet the
      fundamental mechanisms underlying alcohol-mediated brain damage remain unclear.
      The products of alcohol metabolism cause DNA damage, which in conditions of DNA
      repair dysfunction leads to genomic instability and neural death. We propose that
      one-carbon metabolism (OCM) impairment associated with long term chronic ethanol
      intake is a key factor in ethanol-induced neurotoxicity, because OCM provides
      cells with DNA precursors for DNA repair and methyl groups for DNA methylation,
      both critical for genomic stability. Using histological (immunohistochemistry and
      stereological counting) and biochemical assays, we show that 3-week chronic
      exposure of adult mice to 5% ethanol (Lieber-Decarli diet) results in increased
      DNA damage, reduced DNA repair, and neuronal death in the brain. These were
      concomitant with compromised OCM, as evidenced by elevated homocysteine, a marker
      of OCM dysfunction. We conclude that OCM dysfunction plays a causal role in
      alcohol-induced genomic instability in the brain because OCM status determines
      the alcohol effect on DNA damage/repair and genomic stability. Short ethanol
      exposure, which did not disturb OCM, also did not affect the response to DNA
      damage, whereas additional OCM disturbance induced by deficiency in a key OCM
      enzyme, methylenetetrahydrofolate reductase (MTHFR) in Mthfr(+/-) mice,
      exaggerated the ethanol effect on DNA repair. Thus, the impact of long term
      ethanol exposure on DNA repair and genomic stability in the brain results from
      OCM dysfunction, and MTHFR mutations such as Mthfr 677C->T, common in human
      population, may exaggerate the adverse effects of ethanol on the brain.

PMID- 23118225
TI  - Novel Clostridium thermocellum type I cohesin-dockerin complexes reveal a single
      binding mode.
AB  - Protein-protein interactions play a pivotal role in a large number of biological
      processes exemplified by the assembly of the cellulosome. Integration of
      cellulosomal components occurs through the binding of type I cohesin modules
      located in a non-catalytic molecular scaffold to type I dockerin modules located
      at the C terminus of cellulosomal enzymes. The majority of type I dockerins
      display internal symmetry reflected by the presence of two essentially identical
      cohesin-binding surfaces. Here we report the crystal structures of two novel
      Clostridium thermocellum type I cohesin-dockerin complexes (CohOlpC-Doc124A and
      CohOlpA-Doc918). The data revealed that the two dockerins, Doc918 and Doc124A,
      are unusual because they lack the structural symmetry required to support a dual
      binding mode. Thus, in both cases, cohesin recognition is dominated by residues
      located at positions 11, 12, and 19 of one of the dockerin binding surfaces. The
      alternative binding mode is not possible (Doc918) or highly limited (Doc124A)
      because residues that assume the critical interacting positions, when dockerins
      are reoriented by 180 degrees , make steric clashes with the cohesin. In common
      with a third dockerin (Doc258) that also presents a single binding mode, Doc124A
      directs the appended cellulase, Cel124A, to the surface of C. thermocellum and
      not to cellulosomes because it binds preferentially to type I cohesins located at
      the cell envelope. Although there are a few exceptions, such as Doc918 described
      here, these data suggest that there is considerable selective pressure for the
      evolution of a dual binding mode in type I dockerins that direct enzymes into
      cellulosomes.

PMID- 23118226
TI  - Apolipoproteins and apolipoprotein mimetic peptides modulate phagocyte
      trafficking through chemotactic activity.
AB  - The plasma lipoprotein-associated apolipoproteins (apo) A-I and apoE have well
      described anti-inflammatory actions in the cardiovascular system, and mimetic
      peptides that retain these properties have been designed as therapeutics. The
      anti-inflammatory mechanisms of apolipoprotein mimetics, however, are
      incompletely defined. Whether circulating apolipoproteins and their mimetics
      regulate innate immune responses at mucosal surfaces, sites where transvascular
      emigration of leukocytes is required during inflammation, remains unclear.
      Herein, we report that Apoai(-/-) and Apoe(-/-) mice display enhanced recruitment
      of neutrophils to the airspace in response to both inhaled lipopolysaccharide and
      direct airway inoculation with CXCL1. Conversely, treatment with apoA-I (L-4F) or
      apoE (COG1410) mimetic peptides reduces airway neutrophilia. We identify
      suppression of CXCR2-directed chemotaxis as a mechanism underlying the
      apolipoprotein effect. Pursuing the possibility that L-4F might suppress
      chemotaxis through heterologous desensitization, we confirmed that L-4F itself
      induces chemotaxis of human PMNs and monocytes. L-4F, however, fails to induce a
      calcium flux. Further exploring structure-function relationships, we studied the
      alternate apoA-I mimetic L-37pA, a bihelical analog of L-4F with two Leu-Phe
      substitutions. We find that L-37pA induces calcium and chemotaxis through formyl
      peptide receptor (FPR)2/ALX, whereas its D-stereoisomer (i.e. D-37pA) blocks L
      37pA signaling and induces chemotaxis but not calcium flux through an
      unidentified receptor. Taken together, apolipoprotein mimetic peptides are novel
      chemotactic agents that possess complex structure-activity relationships to
      multiple receptors, displaying anti-inflammatory efficacy against innate immune
      responses in the airway.

PMID- 23118227
TI  - Characterization of a flavoprotein oxidase from opium poppy catalyzing the final
      steps in sanguinarine and papaverine biosynthesis.
AB  - Benzylisoquinoline alkaloids are a diverse class of plant specialized metabolites
      that includes the analgesic morphine, the antimicrobials sanguinarine and
      berberine, and the vasodilator papaverine. The two-electron oxidation of
      dihydrosanguinarine catalyzed by dihydrobenzophenanthridine oxidase (DBOX) is the
      final step in sanguinarine biosynthesis. The formation of the fully conjugated
      ring system in sanguinarine is similar to the four-electron oxidations of (S)
      canadine to berberine and (S)-tetrahydropapaverine to papaverine. We report the
      isolation and functional characterization of an opium poppy (Papaver somniferum)
      cDNA encoding DBOX, a flavoprotein oxidase with homology to (S)
      tetrahydroprotoberberine oxidase and the berberine bridge enzyme. A query of
      translated opium poppy stem transcriptome databases using berberine bridge enzyme
      yielded several candidate genes, including an (S)-tetrahydroprotoberberine
      oxidase-like sequence selected for heterologous expression in Pichia pastoris.
      The recombinant enzyme preferentially catalyzed the oxidation of
      dihydrosanguinarine to sanguinarine but also converted (RS)-tetrahydropapaverine
      to papaverine and several protoberberine alkaloids to oxidized forms, including
      (RS)-canadine to berberine. The K(m) values of 201 and 146 MUm for
      dihydrosanguinarine and the protoberberine alkaloid (S)-scoulerine, respectively,
      suggested high concentrations of these substrates in the plant. Virus-induced
      gene silencing to reduce DBOX transcript levels resulted in a corresponding
      reduction in sanguinarine, dihydrosanguinarine, and papaverine accumulation in
      opium poppy roots in support of DBOX as a multifunctional oxidative enzyme in BIA
      metabolism.

PMID- 23118228
TI  - LUZ-Y, a novel platform for the mammalian cell production of full-length IgG
      bispecific antibodies.
AB  - The ability of bispecific antibodies to simultaneously bind two unique antigens
      has great clinical potential. However, most approaches utilized to generate
      bispecific antibodies yield antibody-like structures that diverge significantly
      from the structure of archetype human IgG, and those that do approach structural
      similarity to native antibodies are often challenging to engineer and
      manufacture. Here, we present a novel platform for the mammalian cell production
      of bispecific antibodies that differ from their parental mAbs by only a single
      point mutation per heavy chain. Central to this platform is the addition of a
      leucine zipper to the C terminus of the C(H)3 domain of the antibody that is
      sufficient to drive the heterodimeric assembly of antibody heavy chains and can
      be readily removed post-purification. Using this approach, we developed various
      antibody constructs including one-armed Abs, bispecific antibodies that utilize a
      common light chain, and bispecific antibodies that pair light chains to their
      cognate heavy chains via peptide tethers. We have applied this technology to
      various antibody pairings and will demonstrate the engineering, purification, and
      biological activity of these antibodies herein.

PMID- 23118229
TI  - The enzymatic activity of apoptosis-inducing factor supports energy metabolism
      benefiting the growth and invasiveness of advanced prostate cancer cells.
AB  - Apoptosis-inducing factor (AIF) promotes cell death yet also controls
      mitochondrial homeostasis and energy metabolism. It is unclear how these
      activities are coordinated, and the impact of AIF upon human disease, in
      particular cancer, is not well documented. In this study we have explored the
      contribution of AIF to the progression of prostate cancer. Analysis of archival
      gene expression data demonstrated that AIF transcript levels are elevated in
      human prostate cancer, and we found that AIF protein is increased in prostate
      tumors. Suppression of AIF expression in the prostate cancer cell lines LNCaP,
      DU145, and PC3 demonstrated that AIF does not contribute to cell toxicity via a
      variety of chemical death triggers, and growth under nutrient-rich conditions is
      largely unaffected by AIF ablation. However, under growth stress conditions, AIF
      depletion from DU145 and PC3 cell lines led to significant reductions in cell
      survival and growth that were not observed in LNCaP cells. Moreover AIF-deficient
      PC3 cells exhibited substantial reduction of tumorigenic growth in vivo. This
      reduced survival correlated with decreased expression of mitochondrial complex I
      protein subunits and concomitant changes in glucose metabolism. Finally,
      restoration of AIF-deficient PC3 cells with AIF variants demonstrated that the
      enzymatic activity of AIF is required for aggressive growth. Overall these
      studies show that AIF is an important factor for advanced prostate cancer cells
      and that through control of energy metabolism and redox balance, the enzymatic
      activity of AIF is critical for this support.

PMID- 23118230
TI  - TSG-6 protein is crucial for the development of pulmonary hyaluronan deposition,
      eosinophilia, and airway hyperresponsiveness in a murine model of asthma.
AB  - Hyaluronan (HA) deposition is often correlated with mucosal inflammatory
      responses, where HA mediates both protective and pathological responses. By
      modifying the HA matrix, Tnfip6 (TNF-alpha-induced protein-6; also known as TSG-6
      (TNF-stimulated gene-6)) is thought to potentiate anti-inflammatory and anti
      plasmin effects that are inhibitory to leukocyte extravasation. In this study, we
      examined the role of endogenous TSG-6 in the pathophysiological responses
      associated with acute allergic pulmonary inflammation. Compared with wild-type
      littermate controls, TSG-6(-/-) mice exhibited attenuated inflammation marked by
      a significant decrease in pulmonary HA concentrations measured in the
      bronchoalveolar lavage and lung tissue. Interestingly, despite the equivalent
      induction of both humoral and cellular Th2 immunity and the comparable levels of
      cytokines and chemokines typically associated with eosinophilic pulmonary
      inflammation, airway eosinophilia was significantly decreased in TSG-6(-/-) mice.
      Most importantly, contrary to their counterpart wild-type littermates, TSG-6(-/-)
      mice were resistant to the induction of airway hyperresponsiveness and manifested
      improved lung mechanics in response to methacholine challenge. Our study
      demonstrates that endogenous TSG-6 is dispensable for the induction of Th2
      immunity but is essential for the robust increase in pulmonary HA deposition,
      propagation of acute eosinophilic pulmonary inflammation, and development of
      airway hyperresponsiveness. Thus, TSG-6 is implicated in the experimental murine
      model of allergic pulmonary inflammation and is likely to contribute to the
      pathogenesis of asthma.

PMID- 23118231
TI  - Structural characterization of human cytochrome P450 2C19: active site
      differences between P450s 2C8, 2C9, and 2C19.
AB  - To identify the structural features underlying the distinct substrate and
      inhibitor profiles of P450 2C19 relative to the closely related human enzymes,
      P450s 2C8 and 2C9, the atomic structure (Protein Data Bank code 4GQS) of
      cytochrome P450 2C19 complexed with the inhibitor (2-methyl-1-benzofuran-3-yl)-(4
      hydroxy-3,5-dimethylphenyl)methanone (Protein Data Bank chemical component 0XV)
      was determined to 2.87 A resolution by x-ray crystallography. The conformation of
      the peptide backbone of P450 2C19 is most similar to that of P450 2C8, but the
      substrate-binding cavity of P450 2C8 is much larger than that of P450 2C19 due to
      differences in the amino acid residues that form the substrate-binding cavities
      of the two enzymes. In contrast, the substrate-binding cavity of P450 2C19 is
      much more similar in size to that of the structure of the P450 2C9 flurbiprofen
      complex than to that of a modified P450 2C9 or that of P450 2C8. The cavities of
      the P450 2C19 0XV complex and the P450 2C9 flurbiprofen complex differ, however,
      because the helix B-C loops of the two enzymes are dissimilar. These
      conformational differences reflect the effects of adjacent structural elements
      that interact with the B-C loops and that differ between the two enzymes. The
      availability of a structure for 2C19 will facilitate computational approaches for
      predictions of substrate and inhibitor binding to this enzyme.

PMID- 23118232
TI  - Cancer cells induced to express mesenchymal phenotype release exosome-like
      extracellular vesicles carrying tissue factor.
AB  - Aggressive epithelial cancer cells frequently adopt mesenchymal characteristics
      and exhibit aberrant interactions with their surroundings, including the
      vasculature. Whether the release/uptake of extracellular vesicles (EVs) plays a
      role during these processes has not been studied. EVs are heterogeneous membrane
      structures that originate either at the surface (microparticles), or within
      (exosomes) activated or transformed cells, and are involved in intercellular
      trafficking of bioactive molecules. Here, we show that epithelial cancer cells
      (A431, DLD-1) adopt mesenchymal features (epithelial-to-mesenchymal transition
      like state) upon activation of epidermal growth factor receptor (EGFR) coupled
      with blockade of E-cadherin. This treatment leads to a coordinated loss of EGFR
      and tissue factor (TF) from the plasma membrane and coincides with a surge in
      emission of small, exosome-like EVs containing both receptors. TF (but not EGFR)
      is selectively up-regulated in EVs produced by mesenchymal-like cancer cells and
      can be transferred to cultured endothelial cells rendering them highly
      procoagulant. We postulate that epithelial-to-mesenchymal transition-like changes
      may alter cancer cell interactions with the vascular systems through altered
      vesiculation and TF shedding.

PMID- 23118234
TI  - Toward an ethics of desire for psychoanalysis: introduction to Kirshner.

PMID- 23118233
TI  - Three-dimensional localization of the alpha and beta subunits and of the II-III
      loop in the skeletal muscle L-type Ca2+ channel.
AB  - The L-type Ca(2+) channel (dihydropyridine receptor (DHPR) in skeletal muscle
      acts as the voltage sensor for excitation-contraction coupling. To better resolve
      the spatial organization of the DHPR subunits (alpha(1s) or Ca(V)1.1, alpha(2),
      beta(1a), delta1, and gamma), we created transgenic mice expressing a recombinant
      beta(1a) subunit with YFP and a biotin acceptor domain attached to its N- and C-
      termini, respectively. DHPR complexes were purified from skeletal muscle,
      negatively stained, imaged by electron microscopy, and subjected to single
      particle image analysis. The resulting 19.1-A resolution, three-dimensional
      reconstruction shows a main body of 17 * 11 * 8 nm with five corners along its
      perimeter. Two protrusions emerge from either face of the main body: the larger
      one attributed to the alpha(2)-delta1 subunit that forms a flexible hook-shaped
      feature and a smaller protrusion on the opposite side that corresponds to the II
      III loop of Ca(V)1.1 as revealed by antibody labeling. Novel features discernible
      in the electron density accommodate the atomic coordinates of a voltage-gated
      sodium channel and of the beta subunit in a single docking possibility that
      defines the alpha1-beta interaction. The beta subunit appears more closely
      associated to the membrane than expected, which may better account for both its
      role in localizing the alpha(1s) subunit to the membrane and its suggested role
      in excitation-contraction coupling.

PMID- 23118235
TI  - Representing female desire within a labial framework of sexuality.
AB  - Sexual experiences, rather than being neutral, are specifically male or female.
      Yet at present no conceptual framework exists for representing female sexual
      desire. This has resulted in frequent misrepresentations of female sexual
      experience. To correct this, a labial framework is proposed, not to replace or
      oppose a phallic framework, but to exist alongside it. The lips of the mouth and
      those of the genitals provide a felicitous doubling of sexuality and speech to
      represent female desire and sexual pleasure as labial. Phallic and labial rhythms
      are organized differently in sexual arousal and desire, since, as Simone de
      Beauvoir put it, "Man 'gets stiff,' but woman 'gets wet.'" The labial framework
      therefore represents female psychosexuality more in terms of "wetware" than of
      "hardware."

PMID- 23118237
TI  - A holist's anxiety of influence: commentary on Kirshner.

PMID- 23118238
TI  - The flourishing analyst, responsibility, and psychoanalytic ethics: commentary on
      Kirshner.

PMID- 23118239
TI  - Toward an ethics of psychoanalysis: a critical reading of Lacan's ethics.
AB  - Lacan's seminar The Ethics of Psychoanalysis (1959-1960) pursues, from a Freudian
      perspective, a fundamental philosophical question classically addressed by
      Aristotle's Nichomachean Ethics: How is human life best lived and fulfilled? Is
      there is an ethic of this type intrinsic to psychoanalysis? Lacan placed the
      problem of desire at the center of his Ethics. His notorious self-authorized
      freedom from convention and probable crossing of limits (see Roudinesco 1993) may
      have led mainstream analysts to ignore his admonition: "At every moment we need
      to know what our effective relationship is to the desire to do good, to the
      desire to cure" (Lacan 1959-1960, p. 219). This means that the analyst's desire,
      as well as the patient's, is always in play in his attempt to sustain an ethical
      position. An examination of Lacan's seminar highlights this link, but also points
      to a number of unresolved issues. The patient's desire is a complex matter,
      readily entangled in neurotic compromise, defense, and transference, and the
      analyst's commitment to it is also problematic because of the inevitable co
      presence of his own desire. Lacan suggested that more emphasis be placed in
      training on the desire of the analyst, but beyond that a proposal is advanced for
      the institutionalization of a "third" as reviewer and interlocutor in routine
      analytic practice. Analysis may not be a discipline that can be limited to a
      dyadic treatment relationship.

PMID- 23118240
TI  - Siblings, identity development, and clinical process.

PMID- 23118241
TI  - Archimedean desire: commentary on Kirshner.

PMID- 23118242
TI  - A practice pathway for the identification, evaluation, and management of insomnia
      in children and adolescents with autism spectrum disorders.
AB  - OBJECTIVE: This report describes the development of a practice pathway for the
      identification, evaluation, and management of insomnia in children and
      adolescents who have autism spectrum disorders (ASDs). METHODS: The Sleep
      Committee of the Autism Treatment Network (ATN) developed a practice pathway,
      based on expert consensus, to capture best practices for an overarching approach
      to insomnia by a general pediatrician, primary care provider, or autism medical
      specialist, including identification, evaluation, and management. A field test at
      4 ATN sites was used to evaluate the pathway. In addition, a systematic
      literature review and grading of evidence provided data regarding treatments of
      insomnia in children who have neurodevelopmental disabilities. RESULTS: The
      literature review revealed that current treatments for insomnia in children who
      have ASD show promise for behavioral/educational interventions and melatonin
      trials. However, there is a paucity of evidence, supporting the need for
      additional research. Consensus among the ATN sleep medicine committee experts
      included: (1) all children who have ASD should be screened for insomnia; (2)
      screening should be done for potential contributing factors, including other
      medical problems; (3) the need for therapeutic intervention should be determined;
      (4) therapeutic interventions should begin with parent education in the use of
      behavioral approaches as a first-line approach; (5) pharmacologic therapy may be
      indicated in certain situations; and (6) there should be follow-up after any
      intervention to evaluate effectiveness and tolerance of the therapy. Field
      testing of the practice pathway by autism medical specialists allowed for
      refinement of the practice pathway. CONCLUSIONS: The insomnia practice pathway
      may help health care providers to identify and manage insomnia symptoms in
      children and adolescents who have ASD. It may also provide a framework to
      evaluate the impact of contributing factors on insomnia and to test the
      effectiveness of nonpharmacologic and pharmacologic treatment strategies for the
      nighttime symptoms and daytime functioning and quality of life in ASD.

PMID- 23118243
TI  - Clinical practice pathways for evaluation and medication choice for attention
      deficit/hyperactivity disorder symptoms in autism spectrum disorders.
AB  - BACKGROUND AND OBJECTIVE: Hyperactivity, impulsivity, and inattention (referred
      to as "ADHD [attention-deficit/hyperactivity disorder] symptoms") occur in 41% to
      78% of children with autism spectrum disorders (ASDs). These symptoms often
      affect quality of life, interfering with learning or interventions that target
      primary ASD symptoms. This practice pathway describes the guidelines for
      evaluation and treatment of children and adolescents with ASD and comorbid ADHD
      symptoms. METHODS: Current research in this area is limited, and, therefore,
      these recommendations are based on a systematic literature review and expert
      consensus in the Autism Speaks Autism Treatment Network Psychopharmacology
      Committee. RESULTS: The recommended practice pathway includes the Symptom
      Evaluation Pathway for systematic assessment of ADHD symptoms across settings;
      examination for comorbid sleep, medical, or psychiatric comorbidities that may
      contribute to symptoms; and evaluation of behavioral interventions that may
      ameliorate these symptoms. For children for whom medication is being considered
      to target the ADHD symptoms, the medication choice pathway provides guidance on
      the selection of the appropriate agent based on a review of available research,
      assessment of specific advantages and disadvantages of each agent, and dosing
      considerations. CONCLUSIONS: These recommendations provide a framework for
      primary care providers treating children who have ASD and ADHD symptoms. Our
      systematic review of the current evidence indicates the need for more randomized
      controlled trials of the medications for ADHD symptoms in ASD. There will also be
      a need for studies of the effectiveness of these practice pathways in the future.

PMID- 23118244
TI  - Effects of a standardized pamphlet on insomnia in children with autism spectrum
      disorders.
AB  - OBJECTIVE: Sleep difficulties are common reasons why parents seek medical
      intervention in children with autism spectrum disorders (ASDs). We determined
      whether a pamphlet alone could be used by parents to help their child's insomnia.
      METHODS: Thirty-six children with ASD, ages 2 to 10 years, were enrolled. All had
      prolonged sleep latency confirmed by actigraphy showing a mean sleep latency of
      30 minutes or more. Parents were randomly assigned to receive the sleep education
      pamphlet or no intervention. Children wore an actigraphy device to record
      baseline sleep parameters, with the primary outcome variable being change in
      sleep latency. Actigraphy data were collected a second time 2 weeks after the
      parent received the randomization assignment and analyzed by using Student's t
      test. Parents were also asked a series of questions to gather information about
      the pamphlet and its usefulness. RESULTS: Although participants randomized to the
      2 arms did not differ statistically in age, gender, socioeconomic status, total
      Children's Sleep Habits Questionnaire score, or actigraphy parameters, some
      differences may be large enough to affect results. Mean change in sleep-onset
      latency did not differ between the randomized groups (pamphlet versus no
      pamphlet). Parents commented that the pamphlet contained good information, but
      indicated that it would have been more useful to be given specific examples of
      how to take the information and put it into practice. CONCLUSIONS: A sleep
      education pamphlet did not appear to improve sleep latency in children with ASDs.

PMID- 23118245
TI  - Nutrient intake from food in children with autism.
AB  - OBJECTIVE: The impact of abnormal feeding behaviors reported for children with
      autism spectrum disorders (ASDs) on their nutritional status is unknown. We
      compared nutrient intake from food consumed by children with and without ASD and
      examined nutrient deficiency and excess. METHODS: Prospective 3-day food records
      and BMI for children (2-11 years) with ASD participating in the Autism Treatment
      Network (Arkansas, Cincinnati, Colorado, Pittsburgh, and Rochester) were compared
      with both the National Health and Nutrition Examination Survey data and a matched
      subset based on age, gender, family income, and race/ethnicity (N = 252 analyzed
      food records). RESULTS: Children with ASD and matched controls consumed similar
      amounts of nutrients from food. Only children with ASD aged 4 to 8 years consumed
      significantly less energy, vitamins A and C, and the mineral Zn; and those 9 to
      11 years consumed less phosphorous. A greater percentage of children with ASD met
      recommendations for vitamins K and E. Few children in either group met the
      recommended intakes for fiber, choline, calcium, vitamin D, vitamin K, and
      potassium. Specific age groups consumed excessive amounts of sodium, folate,
      manganese, zinc, vitamin A (retinol), selenium, and copper. No differences were
      observed in nutritional sufficiency of children given restricted diets. Children
      aged 2 to 5 years with ASD had more overweight and obesity, and children 5 to 11
      years had more underweight. CONCLUSIONS: Children with ASD, like other children
      in America, consume less than the recommended amounts of certain nutrients from
      food. Primary care for all children should include nutritional surveillance and
      attention to BMI.

PMID- 23118247
TI  - Gastrointestinal conditions in children with autism spectrum disorder: developing
      a research agenda.

PMID- 23118246
TI  - Iron status in children with autism spectrum disorder.
AB  - BACKGROUND AND OBJECTIVES: Children with autism spectrum disorders (ASDs) often
      have food selectivity and restricted diets, putting them at risk for nutritional
      deficiencies. Previous studies have demonstrated a high prevalence of iron
      deficiency (ID) in children with ASDs living in Wales, Canada, and Turkey. The
      objectives of this study were to determine the prevalence of ID and the adequacy
      of iron intake in children with ASD in the United States. METHODS: Participants
      (age 2-11 years recruited from the Autism Treatment Network Diet and Nutrition
      Study) completed a 3-day diet record (n = 368) and had laboratory measures of
      serum ferritin (SF), complete blood count, iron, total iron binding capacity, and
      transferrin saturation (TS) (n = 222). RESULTS: Of the 222 participants with
      laboratory data, 18 (8%) had SF <12 ug/L and 2 (1%) had ID defined by both low SF
      and TS (3 children with low SF had missing TS data). One subject had iron
      deficiency anemia. Fewer than 2% of subjects had iron intake below the estimated
      average requirement. CONCLUSIONS: Although the determination of iron status is
      complex, these data do not support previous reports that children with ASD are at
      greater risk for ID than the general population; however, 8% percent of the
      sample did demonstrate low SF despite <2% of the sample demonstrating iron intake
      below the estimated average requirement. The prevalence of low SF may be an
      underestimate, because SF is an acute phase reactant and the study included no
      measure of inflammation.

PMID- 23118248
TI  - Nonmedical interventions for children with ASD: recommended guidelines and
      further research needs.
AB  - OBJECTIVE: To use the findings of a systematic review of scientific evidence to
      develop consensus guidelines on nonmedical interventions that address cognitive
      function and core deficits in children with autism spectrum disorders (ASDs) and
      to recommend priorities for future research. METHODS: The guidelines were
      developed by a Technical Expert Panel (TEP) consisting of practitioners,
      researchers, and parents. A systematic overview of research findings was
      presented to the TEP; guideline statements were drafted, discussed, debated,
      edited, reassessed, and presented for formal voting. RESULTS: The strength of
      evidence of efficacy varied by intervention type from insufficient to moderate.
      There was some evidence that greater intensity of treatment (hours per week) and
      greater duration (in months) led to better outcomes. The TEP agreed that children
      with ASD should have access to at least 25 hours per week of comprehensive
      intervention to address social communication, language, play skills, and
      maladaptive behavior. They agreed that applied behavioral analysis, integrated
      behavioral/developmental programs, the Picture Exchange Communication System, and
      various social skills interventions have shown efficacy. Based on identified
      gaps, they recommend that future research focus on assessment and monitoring of
      outcomes, addressing the needs of pre/nonverbal children and adolescents, and
      identifying the most effective strategies, dose, and duration to improve specific
      core deficits. CONCLUSIONS: The creation of treatment guidelines and
      recommendations for future research represents an effort by leading experts to
      improve access to services for children with ASDs while acknowledging that the
      research evidence has many gaps.

PMID- 23118249
TI  - Is inclusivity an indicator of quality of care for children with autism in
      special education?
AB  - OBJECTIVE: To determine whether the proportion of time spent in an inclusive
      educational setting, a process indicator of the quality of schooling for children
      with autism, improves key outcomes. METHODS: Patients were 484 children and youth
      educated in special education with a primary diagnosis of autism in the National
      Longitudinal Transition Study-2. These individuals were ages 20 to 23 in 2007. We
      used propensity-score inverse probability of treatment weights to eliminate the
      effect of multiple confounders. A causal interpretation of the effect of
      inclusivity on key educational and functional outcomes still depends on a
      critical assumption, that inclusivity is not confounded by remaining, omitted
      confounders. RESULTS: Compared with children with autism who were not educated in
      an inclusive setting (n = 215), children with autism who spent 75% to 100% of
      their time in a general education classroom (n = 82) were no more likely to
      attend college (P = .40), not drop out of high school (P = .24), or have an
      improved functional cognitive score (P = .99) after controlling for key
      confounders. CONCLUSIONS: We find no systematic indication that the level of
      inclusivity improves key future outcomes. Research on educational and functional
      outcomes for children with autism can benefit from data on large samples of
      children educated in real-world settings, such as the National Longitudinal
      Transition Study-2, but more nuanced indicators should be developed to measure
      the quality of special education for children with autism.

PMID- 23118250
TI  - Long-term outcomes of toddlers with autism spectrum disorders exposed to short
      term intervention.
AB  - OBJECTIVES: To examine long-term outcomes of toddlers with autism spectrum
      disorder (ASD) who received a 6-month early intervention at age 2. METHODS: Forty
      eight toddlers diagnosed with an ASD received a 6-month evidence-based
      intervention. Cognitive (IQ) and communication ability, as well as severity of
      autism symptoms, were assessed by using standardized measures at preintervention
      (Time 1 [T1]; mean [M] age = 27 months), postintervention (T2; M age = 35
      months), short-term follow-up (T3; M age = 41 months), and long-term follow-up
      (T4; M age = 72 months). RESULTS: From pre- to postintervention, significant
      gains in IQ and Vineland Communication domain standard scores as well as a
      reduction in ASD severity were achieved (all P < .01). Between T2 and T3, the 6
      month period immediately after completion of the intervention, IQ and
      Communication scores stabilized and ASD severity increased significantly (P <
      .05). During the long-term follow-up period (T3-T4), IQ and Communication scores
      significantly increased again, but ASD severity increased significantly as well
      (all P < .05). For overall trajectory (T1-T4), robust gains were observed for
      both IQ and communication; ASD severity did not change. CONCLUSIONS: Findings
      highlight the potential for positive long-term outcomes in toddlers with ASD.
      Additional research is needed to understand the relation between early exposure
      to uninterrupted intervention and developmental gains, and whether initial
      reduction in ASD symptom severity can be sustained through targeted intervention.

PMID- 23118251
TI  - Autism spectrum disorders and developmental disabilities in children from
      immigrant families in the United States.
AB  - OBJECTIVES: Recent census data show that nearly one-quarter of US children have
      at least 1 immigrant parent; moreover, there has been a dramatic increase in
      children diagnosed with autism spectrum disorders (ASDs) and select developmental
      disabilities (DDs). However, little is known about access to medical home and
      adequacy of insurance coverage for children with ASDs and select DDs from
      immigrant families. METHODS: By using the 2007 National Survey of Children's
      Health, we compared children with ASDs and select DDs from immigrant (n = 413,
      foreign born or reside with at least 1 immigrant parent) and nonimmigrant (n =
      5411) families on various measures of medical home and insurance coverage. We
      used weighted logistic regression to examine the association between immigrant
      family and selected outcome measures while controlling for confounding factors.
      RESULTS: Compared with nonimmigrant families, children with ASD and select DD
      from immigrant families were more than twice as likely to lack usual source of
      care and report physicians not spending enough time with family. Furthermore,
      multivariable analyses indicate that insurance coverage is an important factor in
      mitigating health care barriers for immigrant families. CONCLUSIONS: The study
      demonstrates important areas of deficits in the health care experiences of
      children with ASD and select DD from immigrant households. Public policy
      implications include increasing access to existing insurance programs, augmenting
      public awareness resources for ASD and select DD, and offering assistance to
      immigrant families that are struggling with the medical needs of their children.

PMID- 23118252
TI  - The Autism Treatment Network and Autism Intervention Research Network on Physical
      Health: future directions.

PMID- 23118253
TI  - Improving health care for children and youth with autism and other
      neurodevelopmental disorders. Editors' note and prologue.

PMID- 23118254
TI  - Autism Intervention Research Programs of the Maternal and Child Health Bureau.

PMID- 23118255
TI  - Leadership in health care, research, and quality improvement for children and
      adolescents with autism spectrum disorders: Autism Treatment Network and Autism
      Intervention Research Network on Physical Health.

PMID- 23118256
TI  - Use of psychotropic medication in children and adolescents with autism spectrum
      disorders.
AB  - OBJECTIVES: The goal of this study was to examine rates of psychotropic
      medication use and identify associated child and family characteristics among
      children and adolescents with autism spectrum disorder (ASD) enrolled in an
      autism registry maintained by the Autism Treatment Network (ATN). METHODS: The
      sample, derived from the ATN registry, consists of 2853 children aged 2 to 17
      years with diagnoses of ASD supported by Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition, and the Autism Diagnostic Observation Schedule
      with available data on medication use. As part of initial enrollment in the
      registry, parents completed questionnaires on current psychotropic medication
      use, psychiatric and medical conditions, and demographics. RESULTS: Of the 2853
      children, 763 (27%) were taking >= 1 psychotropic medication; 15% were prescribed
      1 medication, 7.4% received 2 medications, and 4.5% received >= 3. Among children
      aged 3 to 5 years, 11% were taking >= 1 psychotropic medication; among 6- to 11
      year-old children, 46%; and 66% of adolescents aged 12 to 17 years were taking at
      >= 1 psychotropic medication. A parent report of comorbid diagnosis of attention
      deficit/hyperactivity disorder, bipolar disorder, obsessive-compulsive disorder,
      depression, or anxiety was associated with a high rate of use, with 80% receiving
      >= 1 psychotropic medication. Only 15% of children with no comorbid psychiatric
      disorder were taking psychotropic medication. Psychotropic medication use was
      also related to sleep and gastrointestinal problems. CONCLUSIONS: The
      prescription of psychotropic medications in this registry sample is highly
      related to comorbid psychiatric disorder. Other factors associated with use
      include medical comorbidities, race, ethnicity, and older age.

PMID- 23118257
TI  - Complementary and alternative medicine use in a large pediatric autism sample.
AB  - BACKGROUND AND OBJECTIVE: Children and adolescents with autism spectrum disorder
      (ASD) often use complementary and alternative medicine (CAM), usually along with
      other medical care. This study aimed to determine associations of ASD diagnostic
      category, co-existing conditions, and use of medications with use of CAM.
      METHODS: We used the Autism Speaks Autism Treatment Network patient registry,
      which collects information on CAM use, medical conditions, and psychotropic
      medication at enrollment. CAM was categorized as special diets versus "other"
      CAM; ASD was defined as autism, pervasive developmental disorder (PDD), or
      Asperger's. Gastrointestinal symptoms, seizure disorders, sleep problems, and
      medication use were determined from parent report. Child Behavior Checklist
      (CBCL) scores were used to measure behavioral symptoms. Logistic regression was
      used to determine associations of diagnostic category, other medical conditions,
      and medication use with CAM treatments, controlling for demographic
      characteristics. RESULTS: Of 3413 subjects in the registry as of April 2011, 3173
      had complete data on CAM use: 896 (28%) reported any use; 548 (17%), special
      diets; and 643 (20%), other CAM. Higher rates of CAM use were associated with
      gastrointestinal symptoms (odds ratio [OR] = 1.88), seizures (OR = 1.58), and
      CBCL total score >70 (OR = 1.29). Children with PDD (OR = 0.62), Asperger's (OR =
      0.66), or using medications (0.69) had lower rates. CONCLUSIONS: Children with
      ASD use more CAM when they have co-existing gastrointestinal symptoms, seizure
      disorders, and behavior problems. This study suggests the importance of asking
      about CAM use in children with ASD, especially those with complex symptoms.

PMID- 23118258
TI  - The relationship between sleep problems and daytime behavior in children of
      different ages with autism spectrum disorders.
AB  - BACKGROUND: The purpose of the current study was to evaluate the relationships
      among sleep problems and daytime behaviors in a large, well-defined cohort of
      children with autism spectrum disorder (ASD). METHODS: Out of a registry
      population of 3452 children with ASDs, a subset of 1193 children aged 4 to 10
      years of age from 14 centers across the country was used to evaluate the
      relationship between varying levels of sleep problems and daytime behavior.
      Measures included Children's Sleep Habits Questionnaire, Vineland Adaptive
      Behavior Scales, Survey Interview Form, Second Edition, and Child Behavior
      Checklist. Multiple analysis of covariance was used to assess the association
      between sleep and behavior. RESULTS: Results suggest that sleep problems, as
      identified by parent report by use of the Children's Sleep Habits Questionnaire,
      have a negative relationship with daytime behavior. More specifically, children
      with ASDs and sleep problems had more internalizing and externalizing behavior
      problems, as measured by the Child Behavior Checklist, and poorer adaptive skill
      development, as measured by the Vineland Adaptive Behavior Scales, than children
      with ASDs and no sleep problems. Children with moderate to severe sleep problems
      had greater behavior difficulties, but not necessarily poorer adaptive
      functioning, than children with mild to moderate sleep problems. Both preschool-
      and school-aged children demonstrated a negative relationship between behavior
      and sleep, whereas the relationship between sleep and adaptive functioning was
      much more variable. CONCLUSIONS: These results suggest that, although sleep has a
      negative relationship with internalizing and externalizing behavior, it may have
      a different relationship with the acquisition of adaptive skills.

PMID- 23118259
TI  - Attention-deficit/hyperactivity disorder symptoms, adaptive functioning, and
      quality of life in children with autism spectrum disorder.
AB  - OBJECTIVE: The purpose of the current study was to evaluate the frequency of co
      occurring attention-deficit/hyperactivity disorder (ADHD) symptoms in a well
      defined cohort of children with autism spectrum disorders (ASDs) and to examine
      the relationship between ADHD symptoms and both adaptive functioning and health
      related quality of life as reported by parents or other primary caregivers.
      METHODS: T scores on 2 ADHD-related scales from the Child Behavior Checklist were
      used to indicate the presence of ADHD symptoms. Participants were divided into
      groups based on whether their parents/caregivers rated them as having clinically
      significant T scores on the Attention Problem and Attention Deficit Hyperactivity
      Problem subscales. Standard scores from the Vineland Adaptive Behavior Scales,
      Second Edition and raw scores from the Pediatric Quality of Life Inventory were
      then compared between groups with the use of multivariate analyses. RESULTS:
      Approximately 40% of participants had 1 elevated T score, and 19% had both ADHD
      related T scores elevated on the Child Behavior Checklist. The ASD + ADHD group
      had lower scores on the Vineland Adaptive Behavior Scales, Second Edition and the
      Pediatric Quality of Life Inventory in comparison with the ASD alone group.
      CONCLUSIONS: Results suggest greater impairment in adaptive functioning and a
      poorer health-related quality of life for children with ASDs and clinically
      significant ADHD symptoms in comparison with children with ASDs and fewer ADHD
      symptoms. Physicians are encouraged to evaluate for the presence of ADHD symptoms
      in their patients with ASDs and, if present, include symptom treatment in the
      overall care plan.

PMID- 23118260
TI  - Management of constipation in children and adolescents with autism spectrum
      disorders.
AB  - OBJECTIVES: To develop a practical, readily applied algorithm for primary health
      care providers to identify, evaluate, and manage constipation in children with
      autism spectrum disorders (ASDs). METHODS: The Gastroenterology Committee of the
      Autism Speaks Autism Treatment Network (ATN), a multisite consortium of centers
      dedicated to improving standards of medical care for children with ASDs, guided
      the development of the constipation algorithm through expert opinion and
      literature review. The algorithm was finalized based on results of field testing
      by nongastrointestinal, ATN autism medical specialists at 4 ATN sites. A
      systematic review and grading of the literature pertaining to constipation and
      children with ASDs was also performed. RESULTS: Consensus among the ATN
      Gastroenterology Committee identified that in children with ASDs, (1) subtle or
      atypical symptoms might indicate the presence of constipation; (2) screening,
      identification, and treatment through a deliberate approach for underlying causes
      of constipation is appropriate; (3) diagnostic-therapeutic intervention can be
      provided when constipation is documented; and (4) careful follow-up after any
      intervention be performed to evaluate effectiveness and tolerance of the therapy.
      Literature review revealed limited evidence for the clinical evaluation or
      treatment strategies of children with ASD and constipation. CONCLUSIONS:
      Constipation and its underlying etiology have the potential to be effectively
      identified and managed using a systematic approach. Lack of evidence on this
      topic in the literature emphasizes the need for research.

PMID- 23118261
TI  - Therapeutic application of monoclonal antibodies in cancer: advances and
      challenges.
AB  - INTRODUCTION: Monoclonal antibody (mAb)-based products are highly specific for a
      particular antigen. This characteristic feature of the molecules makes them an
      ideal tool for many applications including cancer diagnosis and therapy. SOURCES
      OF DATA: We performed comprehensive searches of PubMed, Medline and the Food and
      Drug Administration website using keywords such as 'therapeutic antibodies' and
      'anti-cancer antibodies'. AREAS OF AGREEMENT: Treatment of cancer patients with
      antibodies when used alone or in combination with chemotherapy and radiotherapy,
      or conjugated to drugs or radioisotopes, prolongs overall survival in cancer
      patients. Currently, there are 14 mAb-based drugs that have been approved for the
      treatment of cancer patients. AREAS OF CONTROVERSY: The response of cancer
      patients to antibody therapy can be of short duration. Therapeutic antibodies are
      expensive and may have side effects. There are no reliable predictive biomarkers
      for sensitivity or resistance to certain therapeutic antibodies. FUTURE FOCUS:
      There should be additional studies to discover novel therapeutic targets, to
      develop more effective antibody-based drugs with fewer side effects, to identify
      more reliable predictive biomarker(s) for response to therapy with antibody-based
      drugs and to develop alternative strategies (e.g. transgenic plants, transgenic
      farm animals) for production of large quantities and more affordable batches of
      therapeutic antibodies. AREAS TIMELY FOR DEVELOPING RESEARCH: A better
      understanding of cancer biology, the hallmarks of human cancers and the immune
      system would lead to identification of additional cell surface biomarkers. These
      in turn would facilitate the development of novel and biosimilar antibody-based
      drugs and their routine use as 'magic bullets' for the targeted therapy of human
      cancers.

PMID- 23118262
TI  - Renal complications of diabetes.
AB  - INTRODUCTION: Diabetic nephropathy is a leading cause of chronic kidney disease
      (CKD) in the UK. These patients are at significantly increased risk of
      cardiovascular disease and of progression to end-stage renal disease. We review
      the epidemiology, pathogenesis and natural history of diabetic nephropathy and
      evaluate the therapeutic options available. SOURCES OF DATA: We searched Medline
      and PubMed for source articles relevant to diabetic nephropathy and CKD. AREAS OF
      AGREEMENT: Early multifactorial intervention including strict blood pressure
      control, the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin
      two-receptor blockers (A2RB's) and good metabolic control attenuates
      cardiovascular risk and slows the rate of progression of renal disease. AREAS OF
      CONTROVERSY: Current areas of uncertainty include the relative benefits of ACE
      inhibitors and A2RBs in combination, whether direct renin inhibitors are harmful
      in patients with diabetes and also the positioning of hypoglycaemic agents as
      renal function declines. GROWING POINTS: What are the appropriate metabolic and
      blood pressure targets for patients with diabetes? AREAS TIMELY FOR DEVELOPMENT:
      Therapeutic strategies as kidney function declines.

PMID- 23118263
TI  - "Creating Futures" in Papua New Guinea: just the beginning.
AB  - OBJECTIVES: "Creating Futures 2012: PNG" was the largest mental health conference
      to date in Melanesia. This paper describes the history, purpose and content of
      this initiative as a means to facilitate capacity building in Papua New Guinea
      (PNG), increase binational cooperation and develop a regional mental health
      network. CONCLUSIONS: Fifty Australian professionals were recruited to work with
      PNG colleagues to develop a suite of 20 workshops on locally identified themes.
      Over 300 delegates from across PNG and the western Pacific attended the four-day
      meeting, which was framed by Professor Vikram Patel in a series of presentations
      on global health. Feedback from PNG delegates and potential ongoing activities
      are described.

PMID- 23118265
TI  - Does the disorder matter? Investigating a moderating effect on coached
      noncredible overreporting using the MMPI-2 and PAI.
AB  - The use of psychological tests to help identify the noncredible overreporting of
      psychiatric disorders is a long-standing practice that has received considerable
      attention from researchers. The purpose of this study was to experimentally
      determine whether feigning specific psychiatric disorders moderated the influence
      of coaching on the detection of noncredible overreporting using the Minnesota
      Multiphasic Personality Inventory-2 (MMPI-2) and the Personality Assessment
      Inventory (PAI). Using a 2 * 3 experimental analogue design, 265 undergraduates
      were asked to feign schizophrenia, posttraumatic stress disorder, or generalized
      anxiety disorder and were either coached about validity scales and disorders or
      not. The results of this study indicated that the specific psychiatric disorder
      being feigned did moderate the impact coaching had on the detection of
      overreported psychopathology using several scales on the MMPI-2 and PAI. Future
      research examining noncredible overreporting should take into account the impact
      caused by the interaction of psychiatric disorder with coaching on the detection
      of symptom overreporting and also identify other important moderating/mediating
      variables in order to develop more effective means of identifying response bias.

PMID- 23118266
TI  - The effect of client ethnicity on clinical interpretation of the MMPI-2.
AB  - Client ethnicity has been shown to affect clinicians' diagnostic impressions.
      However, it is not known whether interpretation of the Minnesota Multiphasic
      Personality Inventory-2 (MMPI-2) clinical scales is affected by ethnic bias. In
      this study, clinicians (82 males, 60 females) provided severity ratings for six
      symptoms based on three MMPI-2 profiles (representing the 27/72, 49/94, and 68/86
      code-types) with the ethnicity of the client randomly assigned as either African
      American or Caucasian. To determine whether symptom severity ratings based on
      MMPI-2 profiles were affected by ethnicity, a 3 (code-type) * 2 (ethnicity)
      MANOVA was performed. Neither the main effect for ethnicity nor the ethnicity *
      code-type interaction was significant. These results indicated that the symptom
      severity ratings based on the MMPI-2 clinical scales were not affected by the
      client's identification as African American or Caucasian. Future studies are
      needed to explore the interpretation of profiles from clients representing other
      ethnic groups and for female clients.

PMID- 23118267
TI  - Factorial validity and invariance of the GHQ-12 among clinical and nonclinical
      samples.
AB  - The purpose of this study was to examine the internal reliability, factorial
      validity, and measurement invariance of a Brazilian-Portuguese version of the
      General Health Questionnaire-12 (GHQ-12) across clinical and nonclinical groups.
      The clinical sample consisted of 228 chronic hemodialysis patients (41.7%
      female), with a mean age of 48.23 (SD = 16.02) years, whereas the nonclinical
      sample comprised 350 university students (59.1% female), with a mean age of 21.15
      (SD = 2.04) years. Initial model fit comparison of 16 factor structures reported
      in the literature, through confirmatory factor analysis (CFA), provided mixed
      results. Additional revisions based on CFA modification indices demonstrated that
      a reduced (8-item) one-factor model with three error covariances provided the
      best fit to the data in both samples (comparative fit index > .98 and root mean
      square error of approximation < .05) and acceptable internal reliability
      estimates (>.70). Pearson's correlations between the original and the reduced
      scale was .96 for both samples. Multigroup analysis supported partial strong
      measurement equivalence across groups. Latent mean differences showed an expected
      higher factor mean for the clinical sample. Overall results demonstrated that the
      8-item one-factor of the GHQ-12 showed good psychometric properties in both
      samples and provided preliminary support for meaningful comparisons of factor
      means across clinical and nonclinical groups.

PMID- 23118268
TI  - Effects of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein
      D-conjugate vaccine on nasopharyngeal bacterial colonization in young children: a
      randomized controlled trial.
AB  - BACKGROUND: This study evaluated the effects of the 10-valent pneumococcal
      nontypeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) on
      nasopharyngeal bacterial colonization compared with the 7-valent pneumococcal
      conjugate vaccine (7vCRM) in young children. METHODS: A randomized controlled
      trial in the Netherlands, initiated 2 years after 7vCRM introduction, was
      conducted between 1 April 2008 and 1 December 2010. Infants (N = 780) received
      either PHiD-CV or 7vCRM (2:1) at 2, 3, 4, and 11-13 months of age. Nasopharyngeal
      samples taken at 5, 11, 14, 18, and 24 months of age were cultured to detect
      Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and
      Staphylococcus aureus. Polymerase chain reaction assays quantified H. influenzae
      and S. pneumoniae and confirmed H. influenzae as nontypeable (NTHi). Primary
      outcome measure was vaccine efficacy (VE) against NTHi colonization. RESULTS: In
      both groups, NTHi colonization increased with age from 33% in 5-month-olds to 65%
      in 24-month-olds. Three months postbooster, VE against colonization was 0.5% (95%
      confidence interval [CI], -21.8% to 18.4%) and VE against acquisition 10.9% (95%
      CI, -31.3% to 38.9%). At each sampling moment, no differences between groups in
      either NTHi prevalence or H. influenzae density were detected. Streptococcus
      pneumoniae (range, 39%-57%), M. catarrhalis (range, 63%--69%), and S. aureus
      (range, 9%-30%) colonization patterns were similar between groups. CONCLUSIONS:
      PHiD-CV had no differential effect on nasopharyngeal NTHi colonization or H.
      influenzae density in healthy Dutch children up to 2 years of age, implying that
      herd effects for NTHi are not to be expected. Other bacterial colonization
      patterns were also similar.

PMID- 23118269
TI  - Response to therapy following retreatment of serofast early syphilis patients
      with benzathine penicillin.
AB  - Persistent nontreponemal titers after treatment are common among patients with
      early syphilis. We retreated 82 human immunodeficiency virus-negative early
      syphilis participants who were serofast at 6 months using benzathine penicillin.
      Only 27% exhibited serological response after retreatment and after an additional
      6 months of follow-up.

PMID- 23118270
TI  - Infectious disease burden and vaccination needs among asylees versus refugees,
      district of columbia.
AB  - BACKGROUND: Unlike US-bound refugees, asylum seekers (asylees) apply for asylum
      while residing in the United States and are not provided a medical screening.
      Infectious disease burden and vaccination needs have not been described among US
      asylees. METHODS: We conducted a retrospective cohort study of 630 asylees and
      151 refugees referred to the District of Columbia (DC) Department of Health
      screening program for an initial US medical screening during September 2003
      August 2007. We assessed the prevalence of latent tuberculosis infection
      (tuberculin skin test reactivity >=10 mm), human immunodeficiency virus (HIV) and
      hepatitis B seropositivity, intestinal parasite test positivity, need for
      vaccinations, and time from date of US arrival to receipt of screening. RESULTS:
      Asylees in DC had a similar prevalence as refugees of latent tuberculosis
      infection (39% vs 38%, respectively, P = .83), pathogenic intestinal parasites
      (4% vs 2%, P = .36), and need for adult vaccinations (80% vs 80%, P = .95).
      Asylees were screened significantly later after US arrival compared with refugees
      (55 weeks vs 1 week, P < .001). Asylees had higher prevalence of latent
      tuberculosis infection, hepatitis B and HIV seropositivity, and child and adult
      vaccination needs than the US population (P < .001). CONCLUSIONS: This study of
      the infectious disease concerns of a US asylee population suggests that in DC,
      asylees have similar infectious disease burden and prevention needs as refugees
      and should be screened with the same urgency. Because applicants for US asylum
      are not linked to prompt medical screenings, DC asylees are typically screened
      much later, placing them and US communities at risk.

PMID- 23118271
TI  - Forecasting high-priority infectious disease surveillance regions: a
      socioeconomic model.
AB  - BACKGROUND: Few researchers have assessed the relationships between socioeconomic
      inequality and infectious disease outbreaks at the population level globally. We
      use a socioeconomic model to forecast national annual rates of infectious disease
      outbreaks. METHODS: We constructed a multivariate mixed-effects Poisson model of
      the number of times a given country was the origin of an outbreak in a given
      year. The dataset included 389 outbreaks of international concern reported in the
      World Health Organization's Disease Outbreak News from 1996 to 2008. The initial
      full model included 9 socioeconomic variables related to education, poverty,
      population health, urbanization, health infrastructure, gender equality,
      communication, transportation, and democracy, and 1 composite index. Population,
      latitude, and elevation were included as potential confounders. The initial model
      was pared down to a final model by a backwards elimination procedure. The
      dependent and independent variables were lagged by 2 years to allow for
      forecasting future rates. RESULTS: Among the socioeconomic variables tested, the
      final model included child measles immunization rate and telephone line density.
      The Democratic Republic of Congo, China, and Brazil were predicted to be at the
      highest risk for outbreaks in 2010, and Colombia and Indonesia were predicted to
      have the highest percentage of increase in their risk compared to their average
      over 1996-2008. CONCLUSIONS: Understanding socioeconomic factors could help
      improve the understanding of outbreak risk. The inclusion of the measles
      immunization variable suggests that there is a fundamental basis in ensuring
      adequate public health capacity. Increased vigilance and expanding public health
      capacity should be prioritized in the projected high-risk regions.

PMID- 23118272
TI  - Toward improved surveillance: the impact of ventilator-associated complications
      on length of stay and antibiotic use in patients in intensive care units.
AB  - BACKGROUND: Hospitals and quality improvement agencies are vigorously focusing on
      reducing rates of hospital-acquired infection. Ventilator-associated pneumonia
      (VAP) is notoriously difficult to diagnose and surveillance is thwarted by the
      subjectivity of many components of the surveillance definition. Alternative
      surveillance strategies are needed. Ventilator-associated complications (VAC) is
      a simple, objective measure of respiratory deterioration. METHODS: VAC is defined
      by increases in fraction of inspired oxygen (FiO(2)) by >= 15% or positive end
      expiratory pressure (PEEP) by >= 2.5 cm H(2)O lasting >= 2 days after stable or
      decreasing FiO(2) or PEEP lasting >= 2 days. We retrospectively assessed patients
      on mechanical ventilation for >= 48 hours in our study intensive care unit (ICU)
      using electronic medical record data. We analyzed the association between VAC and
      clinical diagnoses, ICU length of stay, duration of mechanical ventilation,
      antibiotic use, and mortality. RESULTS: We assessed 153 patients with VAC and 390
      without VAC. VAC events were associated with significantly increased ICU length
      of stay, duration of mechanical ventilation, and consumption of broad-spectrum
      antibiotics but not with longer hospital stays or ICU mortality. CONCLUSIONS:
      Surveillance for VAP is subjective and labor intensive. VAC is an objective
      measure which can be readily obtained from electronic records. It is associated
      with adverse outcomes and increased broad-spectrum antibiotic usage. VAC may be a
      useful surveillance tool. The utility of VAC prevention bundles merits
      assessment.

PMID- 23118273
TI  - Editorial commentary: forecasting when, where, and possibly why outbreaks are
      likely to occur.

PMID- 23118274
TI  - A preliminary evaluation of repeated exposure for depersonalization and
      derealization.
AB  - Dissociative symptoms including depersonalization and derealization are commonly
      experienced by individuals suffering from panic disorder or posttraumatic stress
      disorder (PTSD). Few studies have been published investigating the specific
      treatment of these symptoms in individuals diagnosed with panic disorder or PTSD,
      despite evidence that the subset of individuals with panic disorder who
      experience depersonalization and derealization report more panic attacks as well
      as greater panic severity and functional impairment. Furthermore, it has been
      shown that these symptoms can impede treatment and recovery in PTSD. Finally,
      recent research has shown that interoceptive exposure generally enhances the
      efficacy of treatment outcome for PTSD and PTSD with comorbid panic. This study
      investigated the use of a novel interoceptive exposure technique for treatment of
      depersonalization and derealization in individuals with high anxiety sensitivity
      and/or symptoms of PTSD. Results indicated significant reductions on six of seven
      items as well as total score on an outcome measure of depersonalization and
      derealization. Thus, this technique appears to hold promise for utilization as a
      form of interoceptive exposure in the treatment of these symptoms.

PMID- 23118275
TI  - Dabigatran and thrombin modulate electrophysiological characteristics of
      pulmonary vein and left atrium.
AB  - BACKGROUND: Dabigatran reduces stroke in atrial fibrillation. Pulmonary veins
      (PVs) and left atrium (LA) play a critical role in the pathophysiology of atrial
      fibrillation. We investigated the effects of thrombin, blood clot solution, and
      dabigatran on PVs and LA. METHODS AND RESULTS: Conventional microelectrodes were
      used to record the action potentials in isolated PV and LA preparations before
      and after the administration of thrombin or blood clot solution in control and
      dabigatran-treated rabbits. Thrombin (0.01, 0.1, and 1 unit/mL), respectively,
      reduced the PV (n=6) spontaneous beating rates from 1.9+/-0.2 to 1.7+/-0.2, 1.6+/
      0.2, and 1.4+/-0.3 Hz (P=0.046). Blood clot solution (0.5% and 5.0%),
      respectively, reduced the PV (n=5) spontaneous beating rates from 2.0+/-0.4 to
      1.8+/-0.4 and 1.3+/-0.3 Hz (P=0.044). Thrombin (0.01, 0.1, and 1 unit/mL) and
      blood clot solution (0.5% and 5.0%) increased LA diastolic tension and the
      resting membrane potential with decreased action potential duration and
      contractility. Thrombin (0.01, 0.1, and 1 unit/mL) and blood clot solution (0.5%
      and 5%) induced delayed after depolarization and burst firing in PVs, but not in
      LA. N(G)-nitro-l-arginine methyl ester (100 MUmol/L) or a protease-activated
      receptor type 1 blocker (BMS 200261, 1 MUmol/L) attenuated the effects of
      thrombin and blood clot solution in PVs and LA. Dabigatran-treated PVs had slower
      spontaneous activity (1.1+/-0.1 Hz; n=10; P=0.0001 versus control). Their
      electrophysiological characteristics were not changed by thrombin (1 unit/mL) and
      blood clot solution (5%). CONCLUSIONS: Thrombin modulates PV and LA electric and
      mechanical characteristics, which were blocked by dabigatran.

PMID- 23118276
TI  - Reflecting on early arthritis.

PMID- 23118277
TI  - Rheumatoid arthritis classification criteria: moving with the times.

PMID- 23118278
TI  - A rheumatologist managing patients with rheumatoid arthritis: an artisan but also
      an artist!

PMID- 23118279
TI  - Osteolytic lesion with thick sclerotic walls and demyelinating polyneuropathy.

PMID- 23118280
TI  - Complete ankylosis in longterm HLA-B27-negative psoriatic arthritis.

PMID- 23118281
TI  - Periostitis in a patient with inflammatory bowel disease.

PMID- 23118282
TI  - Prologue: 2011 Group for Research and Assessment of Psoriasis and Psoriatic
      Arthritis (GRAPPA).
AB  - The 2011 Annual Meeting of the Group for Research and Assessment of Psoriasis and
      Psoriatic Arthritis (GRAPPA) was held in July 2011 in Naples, Italy, and attended
      by rheumatologists, dermatologists, and representatives of biopharmaceutical
      companies and patient groups from around the world. The meeting began with a
      trainee symposium, where 25 rheumatology fellows and dermatology residents
      presented their original research work. Presentations and discussions by GRAPPA
      members during the remaining 2-day meeting included a 2-part discussion of the
      status of psoriatic disease biomarker research, summaries of the GRAPPA Composite
      Exercise and the GRAPPA video projects, a contribution from Italian members on
      their psoriasis and PsA projects, a lengthy discussion of research and
      collaborative initiatives from GRAPPA dermatologists, updates on ultrasound
      imaging in psoriatic disease and on plans to define inflammatory musculoskeletal
      disease, a presentation of the results of a small study of psoriasis and PsA in
      aboriginal people of Peru, and a review of global education and partnering
      opportunities. Introductions to these discussions are included in this prologue.

PMID- 23118283
TI  - GRAPPA Trainees Symposium 2011: a report from the GRAPPA 2011 annual meeting.
AB  - The 2011 annual meeting in Naples, Italy, of the Group for Research and
      Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) began with a Trainees
      Symposium, which has become an important aspect of the meeting. In 2011, 25
      trainees currently involved in research in psoriasis or psoriatic arthritis were
      invited to deliver an oral abstract or poster presentation. We present a brief
      overview of the oral and poster presentations, which show the diversity and focus
      of current research performed by members and trainees of GRAPPA.

PMID- 23118284
TI  - Biomarkers of radiographic progression in psoriatic arthritis: a report from the
      GRAPPA 2011 annual meeting.
AB  - Clinical markers of radiographic progression have been studied in patients with
      psoriatic arthritis (PsA), and results have clearly confirmed the progression of
      radiographic damage over a 2-year period. Biomarkers of radiographic progression
      damage (erosion and new bone formation) have also been identified as a critical
      research issue in these patients. At the 2011 annual meeting of the Group for
      Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), members
      discussed development of a pivotal observational study (PsA Biodam study) to
      determine the validity of several soluble biomarkers in predicting structural
      damage in patients with PsA receiving standard therapies. Specific protocol
      issues discussed were the inclusion criteria, selection of candidate biomarkers,
      timing of sample collection, the primary radiographic outcome measure,
      radiographic scoring methods, possible substudies, and funding strategies.

PMID- 23118285
TI  - Biomarkers for comorbidities in psoriasis: a report from the GRAPPA 2011 annual
      meeting.
AB  - Biomarkers are being recognized that will help identify patients with psoriasis
      who may be destined to develop psoriatic arthritis (PsA). Recent genome-wide
      association studies have identified genes that are common to both psoriasis and
      PsA, as well as differentially expressed in the 2 conditions. Further, biomarkers
      of inflammation and cartilage can differentiate between patients with PsA and
      those with psoriasis without arthritis. An overview of these biomarkers was
      presented at the 2011 annual meeting of the Group for Research and Assessment of
      Psoriasis and Psoriatic Arthritis. Additionally, a report was presented from the
      current database of the International Psoriasis and Psoriatic Arthritis Research
      Team, a group of dermatologists and rheumatologists with the objective to improve
      the lives of patients with psoriasis and PsA.

PMID- 23118286
TI  - GRAPPA Responder Index Project (GRACE): a report from the GRAPPA 2011 annual
      meeting.
AB  - The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis
      (GRAPPA) established the GRAPPA Composite Exercise (GRACE) to compare existing
      and emerging composite disease activity and responder measures. At the GRAPPA
      2010 annual meeting, initial results from this project were presented, and voting
      on available measures took place. At the GRAPPA 2011 meeting, further comparisons
      of new and existing measures were made, along with an outline plan for further
      work.

PMID- 23118287
TI  - Psoriasis and psoriatic arthritis video project: an update from the GRAPPA 2011
      annual meeting.
AB  - Numerous physical examination instruments are used to assess and measure severity
      of psoriasis and psoriatic arthritis (PsA) in practice and in clinical trials.
      The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis
      (GRAPPA) has developed several online training modules used by GRAPPA members and
      investigators participating in psoriasis and PsA research. At the 2011 GRAPPA
      meeting, attendees were updated on the ongoing development of the training
      modules. Several Internet-based multimedia presentations for psoriasis and PsA
      assessments have been completed. Available psoriasis modules include the
      Psoriasis Area and Severity Index (PASI) and Body Surface Area, one 5-point and
      two 6-point Physician Global Assessments, the original and modified Nail
      Psoriasis Severity Index, the Palmar-Plantar Pustular Psoriasis Area and Severity
      Index, the Psoriasis Scalp Severity Index, and the Total Plaque Severity Score.
      Rheumatology modules that demonstrate evaluation of swollen and tender joints,
      enthesitis, and dactylitis are now available, and an axial disease evaluation
      module is near completion. Each video includes the background and rationale for
      each measure, demonstration videos of select examinations, diagrams, and
      photographs to emphasize teaching points, and for most dermatology modules, an
      optional test to assess competence. Preliminary data generated by a pilot study
      of pre- and post-education PASI scoring by experienced and naive physicians and
      patient assessors were presented, revealing improved accuracy of scoring after
      viewing the PASI video. Attendees agreed that additional patient examples with
      more diverse skin types and psoriasis phenotypes, translation to languages other
      than English, and further validation studies are needed.

PMID- 23118288
TI  - Psoriatic arthritis and psoriasis projects in Italy: a report from the GRAPPA
      2011 annual meeting.
AB  - Recent evidence that psoriatic arthritis (PsA) is more frequent and more severe
      than previously thought has led to several studies on genetic susceptibility,
      pathogenesis, clinical spectrum, diagnostic tools, and treatment of PsA.
      Concomitant with these studies has been the development of appropriate
      classification/diagnostic criteria and disease-specific outcome measures for PsA.
      Many Italian rheumatologists have taken part in these efforts by conducting
      collaborative multicenter research projects, which were described at the annual
      meeting of the Group for Research and Assessment of Psoriasis and Psoriatic
      Arthritis (GRAPPA; Naples, Italy, July 2011). Highlights of these Italian
      contributions included performance of CASPAR (ClASsification for Psoriatic
      ARthritis) criteria in early PsA; radiological assessments of axial PsA;
      development and validation of the PASRI (PsA Spondylitis Radiology Index in
      patients with established PsA); and the effect of etanercept on axial
      manifestations of established PsA.

PMID- 23118289
TI  - Exploring priority research areas in psoriasis and psoriatic arthritis from
      dermatologists' perspective: a report from the GRAPPA 2011 annual meeting.
AB  - At the 2011 annual meeting of the Group for Research and Assessment of Psoriasis
      and Psoriatic Arthritis (GRAPPA) in Naples, Italy, the GRAPPA dermatology members
      led discussions on priority research areas in psoriasis and psoriatic arthritis
      (PsA). These discussions centered on 3 primary areas: evaluation of PsA screening
      tools, updates on psoriasis comorbidities, and new developments in genetics and
      comparative effectiveness research. Introductory presentations were followed by
      engaging panel discussions and audience interaction. The members agreed that
      screening tools are highly valuable in early detection of PsA among dermatology
      patients and that efforts are necessary to develop tools suitable for adoption in
      clinical practice. Members also agreed that a collaborative investigation to
      evaluate the effect of psoriasis treatments on cardiovascular comorbidities would
      be highly informative. Finally, the members supported continued efforts to
      explore the genetic basis of psoriasis and more studies focused on comparative
      effectiveness of existing treatments.

PMID- 23118290
TI  - GRAPPA 2011: proceedings from the ultrasound imaging module.
AB  - In a plenary session at the 2011 meeting of the Group for Research and Assessment
      of Psoriasis and Psoriatic Arthritis (GRAPPA) the use of sonography for
      evaluating enthesitis and dactylitis in psoriasis and psoriatic arthritis (PsA)
      was reviewed, and initial proposals were presented to develop ultrasound joint
      indices to assess enthesitis and dactylitis in PsA. Sonography can depict
      ultrastructural morphopathological features of an enthesis and its adjoining
      tissue structures, as well as increased vascularity; candidate entheses were
      proposed for an initial sonographic PsA enthesitis index. Ultrasound also can
      readily demonstrate soft tissue changes, synovitis, erosions, and
      osteoproliferation in dactylitis, and these features were proposed for an initial
      sonographic dactylitis index. A perspective was also presented on a wider
      proposed index including the skin, nail, joint, and enthesis.

PMID- 23118291
TI  - On defining musculoskeletal inflammation: a report from the GRAPPA 2011 annual
      meeting.
AB  - At the 2011 annual meeting of the Group for Research and Assessment of Psoriasis
      and Psoriatic Arthritis (GRAPPA), members discussed the need to develop a
      framework for defining inflammatory arthritis, enthesitis, dactylitis, and
      spondylitis, particularly as they relate to psoriatic arthritis (PsA). GRAPPA
      members first addressed this subject at their 2010 meeting, where the CASPAR
      (ClASsification of Psoriatic ARthritis) criteria were discussed. Although these
      are classification criteria, the CASPAR are also often applied as a diagnostic
      measure by clinicians screening for PsA, particularly its core criterion:
      recognizing the presence of inflammatory musculoskeletal disease. In breakout
      group discussions, GRAPPA members discussed the difficulties in recognizing
      overlapping or mimicking features that may result in underdiagnosing or
      misdiagnosing PsA.

PMID- 23118292
TI  - Psoriasis and psoriatic arthritis in Peruvian aborigines: a report from the
      GRAPPA 2011 annual meeting.
AB  - OBJECTIVE: To determine the presence of psoriasis and psoriatic arthritis (PsA)
      in aboriginal people living in the Andean Mountains of Peru. METHODS: Consecutive
      patients with psoriasis and PsA attending an arthritis clinic in Juliaca, Puno,
      Peru, located 3824 m above sea level were examined. The CASPAR (ClASsification of
      Psoriatic ARthritis) criteria were used for classification of PsA. Diagnosis of
      psoriasis was confirmed by a dermatologist. RESULTS: Seventeen patients [11 (65%)
      men and 6 (35%) women] fulfilled classification criteria for PsA; one patient was
      of European ancestry and is not included in this report. Of the 16 aboriginal
      patients in this report, 5 were natives of Quechua ancestry and one was native
      Aymara. At the time of their first clinic visit, no native patient with PsA had a
      family history of psoriasis or PsA, and all patients exhibited an established
      disease of long duration and severity. Methotrexate was the drug of choice for
      all patients; 2 patients are currently receiving biological therapy. CONCLUSION:
      Contrary to what has been reported in the literature, both psoriasis and PsA are
      present in aboriginal people from the Andean Mountains of Peru. More studies are
      needed to further define the phenotype of these disorders, as well as the
      pathogenetic role of genetic and environmental factors.

PMID- 23118293
TI  - Interleukin 22, a potential therapeutic target for rheumatoid arthritis.

PMID- 23118294
TI  - Differentiation of the clinical features of psoriatic arthritis and fibromyalgia.

PMID- 23118295
TI  - Lower 12-hour trough concentrations of mycophenolic acid in patients with active
      systemic vasculitides taking mycophenolate mofetil.

PMID- 23118296
TI  - Etanercept allergy and anaphylaxis.

PMID- 23118297
TI  - Refractory primary central nervous system vasculitis of childhood: successful
      treatment with infliximab.

PMID- 23118298
TI  - Vasculitis of the female genital tract: not always a localized condition.

PMID- 23118301
TI  - Proteolytic activity by multiple bacterial species isolated from chronic venous
      leg ulcers degrades matrix substrates.
AB  - BACKGROUND: A major feature of chronic wounds is the loss of tissue, with the
      exposure of dermal components preventing primary closure and leading to bacterial
      colonization. Bacterial colonization has been proposed as one of the common
      underlying pathologies present in chronic wounds. The objective of this
      exploratory study was to identify bacteria cultured from chronic venous leg
      ulcers and test for proteolytic activity that degrades matrix substrates. METHOD:
      Bacteria were isolated, cultured, and identified from six subjects (average age =
      62.8 years) over 2-10 months under an approved protocol using swabs and
      microbiological culture media. Proteolytic activity against (a) gelatin, (b) an
      elastin substrate, and (c) a serine/trypsin-sensitive substrate was determined
      using a colorimetric plate assay with an ELISA plate reader and zymography.
      RESULTS: We identified 13 bacteria that expressed proteolytic activity against
      one or more of the tested substrates. Of these, six were Gram-positive
      (Staphylococcus aureus, Enterococcus faecalis, Staphylococcus epidermidis,
      Streptococcus agalactiae, Corynebacterium, and Streptococcus bovis) and seven
      were Gram-negative (Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis,
      Morganella morganii, Klebsiella pneumoniae, Bacteroides fragilis, and Serratia
      marcescens) organisms. Two of these, S. aureus and P. aeruginosa, are recognized
      wound pathogens. CONCLUSIONS: Multiple bacteria species isolated from colonized
      venous leg ulcers have the capacity to secrete proteases capable of degrading
      components of the extracellular matrix important for wound healing. Matrix
      degradation by bacteria may contribute to delays in tissue deposition and repair,
      suggesting that treatment of chronic wounds should include appropriate management
      of colonizing bacteria.

PMID- 23118303
TI  - Content area experts as authors: helpful or harmful for systematic reviews and
      meta-analyses?

PMID- 23118302
TI  - Genome-wide association study evaluating lipoprotein-associated phospholipase A2
      mass and activity at baseline and after rosuvastatin therapy.
AB  - BACKGROUND: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is a
      proinflammatory enzyme bound to low-density lipoprotein cholesterol and other
      circulating lipoproteins. Two measures of Lp-PLA(2), mass and activity, are
      associated with increased cardiovascular risk. Data are sparse regarding genetic
      determinants of Lp-PLA(2) mass and activity, and no prior data are available
      addressing genetic determinants of statin-induced changes for this
      proinflammatory biomarker. METHODS AND RESULTS: We performed a genome-wide
      association study of Lp-PLA(2) mass and activity at baseline and after 12 months
      of rosuvastatin therapy (20 mg/d) among 6851 participants of European ancestry
      from the Justification for Use of Statins in Prevention: an Intervention Trial
      Evaluating Rosuvastatin (JUPITER) and performed replication in a meta-analysis of
      13 664 participants from the Cohorts for Heart and Aging Research in Genomic
      Epidemiology (CHARGE) Consortium. Novel associations were identified and
      replicated at MS4A4E and TMEM49 for baseline Lp-PLA(2) activity with genome-wide
      significant joint P values (P=2.0 * 10(-11) and P=2.9 * 10(-9), respectively). In
      addition, genome-wide associations (P<5 * 10(-8)) were identified and replicated
      for baseline Lp-PLA(2) mass at CETP and for Lp-PLA(2) activity at the APOC1-APOE
      and PLA2G7 loci. Among 2673 statin-allocated participants, both Lp-PLA(2) mass
      and activity were reduced by >30% and low-density lipoprotein cholesterol by 50%
      after 12 months of statin therapy (P<0.001 for both). Variants in ABCG2 and LPA
      were associated with change in statin-induced Lp-PLA(2) activity at genome-wide
      significance but were substantially attenuated after adjustment for statin
      induced changes in lipid levels. CONCLUSIONS: Genome-wide significant
      associations at MS4A4E and TMEM49 may reflect novel influences on circulating
      levels of Lp-PLA(2) activity. In addition, genome-wide significant associations
      with rosuvastatin-induced change in Lp-PLA(2) activity were observed in ABCG2 and
      LPA, likely because of their impact on statin-induced low-density lipoprotein
      cholesterol lowering.

PMID- 23118304
TI  - Rises in healthcare spending: where will it end?

PMID- 23118305
TI  - Use of HbA1c in the diagnosis of diabetes.

PMID- 23118306
TI  - Creating credibility and value in comparative effectiveness research.

PMID- 23118307
TI  - How it feels to withdraw feeding from newborn babies.

PMID- 23118308
TI  - Reforming the regulation of orthopaedic devices in the UK.

PMID- 23118309
TI  - Applying to do research studies in the NHS is to be made easier.

PMID- 23118310
TI  - GMC drops case against man accused of submitting incorrect data about heart
      device to medical journal.

PMID- 23118311
TI  - Local control of nuclear calcium signaling in cardiac myocytes by perinuclear
      microdomains of sarcolemmal insulin-like growth factor 1 receptors.
AB  - RATIONALE: The ability of a cell to independently regulate nuclear and cytosolic
      Ca(2+) signaling is currently attributed to the differential distribution of
      inositol 1,4,5-trisphosphate receptor channel isoforms in the nucleoplasmic
      versus the endoplasmic reticulum. In cardiac myocytes, T-tubules confer the
      necessary compartmentation of Ca(2+) signals, which allows sarcomere contraction
      in response to plasma membrane depolarization, but whether there is a similar
      structure tunneling extracellular stimulation to control nuclear Ca(2+) signals
      locally has not been explored. OBJECTIVE: To study the role of perinuclear
      sarcolemma in selective nuclear Ca(2+) signaling. METHODS AND RESULTS: We report
      here that insulin-like growth factor 1 triggers a fast and independent nuclear
      Ca(2+) signal in neonatal rat cardiac myocytes, human embryonic cardiac myocytes,
      and adult rat cardiac myocytes. This fast and localized response is achieved by
      activation of insulin-like growth factor 1 receptor signaling complexes present
      in perinuclear invaginations of the plasma membrane. The perinuclear insulin-like
      growth factor 1 receptor pool connects extracellular stimulation to local
      activation of nuclear Ca(2+) signaling and transcriptional upregulation through
      the perinuclear hydrolysis of phosphatidylinositol 4,5-biphosphate inositol 1,4,5
      trisphosphate production, nuclear Ca(2+) release, and activation of the
      transcription factor myocyte-enhancing factor 2C. Genetically engineered Ca(2+)
      buffers--parvalbumin--with cytosolic or nuclear localization demonstrated that
      the nuclear Ca(2+) handling system is physically and functionally segregated from
      the cytosolic Ca(2+) signaling machinery. CONCLUSIONS: These data reveal the
      existence of an inositol 1,4,5-trisphosphate-dependent nuclear Ca(2+) toolkit
      located in direct apposition to the cell surface, which allows the local control
      of rapid and independent activation of nuclear Ca(2+) signaling in response to an
      extracellular ligand.

PMID- 23118312
TI  - The trauma still goes on...: the multigenerational legacy of Northern Ireland's
      conflict.
AB  - Numerous studies have been conducted internationally on the subject of
      multigenerational trauma; however, little is currently known about its existence
      in the context of the Northern Ireland conflict. The present study explored the
      outcomes of and mechanisms through which the trauma of one generation impacts on
      subsequent generations in this context. Using an Interpretative Phenomenological
      Approach (IPA), this study examined the subjective experiences, beliefs and
      perceptions of four mothers from Northern Ireland, all of whom had endured trauma
      during their childhoods. Three main master themes emerged: 1. "Attempting to
      cope" addressed how the trauma was dealt with, and how these efforts can be the
      very mechanisms through which multigenerational trauma occurs. Examples include
      hiding the truth, seeing the truth as dangerous, and knowing and not knowing
      about the trauma; 2. "The trauma still goes on" highlighted the negative outcomes
      and consequences of the traumatic experiences within the family such as delayed
      impact, symptoms and anger; and 3. "Strength through adversity" included the more
      positive outcomes of their experiences, such as finding meaning through suffering
      and making efforts to stop the cycle. The results are discussed in terms of the
      existing theories on multigenerational trauma, and implications for practice are
      explored. 

PMID- 23118313
TI  - Adolescent suicide in Australia: rates, risk and resilience.
AB  - Adolescent suicide rates in Australia have fallen significantly during recent
      years. The incidence, however, clearly remains a serious concern for young
      people, parents, professionals and policy makers. Some groups of Australian youth
      appear to be at heightened risk. Adolescents within the welfare system,
      indigenous, rural and refugee youth, along with same sex attracted young people
      often need very careful monitoring and support. Young men continue to take their
      lives more frequently than young women. Prevention programmes in Australia aim to
      develop resilience in young people, families and communities that can serve as
      protection against self harm and suicide. The improvement of mental health
      literacy, a fostering of adolescent self-efficacy and better access to early
      intervention strategies are currently privileged in national and state policies
      related to young people in Australia. More work is needed, however, to achieve a
      well integrated mental health framework capable of effectively addressing
      adolescent suicide prevention into the twenty-first century. 

PMID- 23118314
TI  - Acute gastroenteritis.

PMID- 23118315
TI  - The pediatric role in the care of children in foster and kinship care.

PMID- 23118316
TI  - Chronic recurrent abdominal pain.

PMID- 23118317
TI  - Focus on diagnosis: Dysphagia.

PMID- 23118318
TI  - Research and statistics: qualitative research methods.

PMID- 23118319
TI  - Index of suspicion.

PMID- 23118322
TI  - Hymenoptera stings.

PMID- 23118320
TI  - Aminoglycosides.

PMID- 23118323
TI  - Visual diagnosis: abnormal nails in an infant.

PMID- 23118324
TI  - Hospitalized children's representations of their relationship with nurses and
      doctors.
AB  - This article reports an explorative study which aims to investigate hospitalized
      children's views of their relationships with nurses and doctors. Twenty-seven
      school-aged children and adolescents from 6 to 15 years old in the paediatric
      haematology and oncology ward of an Italian hospital participated in the study.
      Each participant was asked to draw him or herself with a doctor or nurse from the
      ward while they were doing something. The drawings were analysed using Pictorial
      Assessment of Interpersonal Relationships (PAIR) and a qualitative analysis. The
      results showed that the participants viewed their relationships with health
      professionals positively, in particular with the nurses. This relationship was
      perceived as close, intimate, cohesive and without conflict. In some cases it
      became an emotional bond. Finally, this relationship helped the patients to cope
      with painful and uncomfortable medical procedures, which gradually became
      familiar and accepted. The clinical implications of this study are discussed. 

PMID- 23118325
TI  - Post-discharge experiences of children and their families following children's
      surgery.
AB  - Increasing rates of day surgery and decreasing length of hospital stay mean
      children's recovery from surgery extends beyond hospital and into the home. The
      objective of this study is to improve the understanding of experiences of
      children and their families during recovery at home post surgery. This is an
      exploratory, interpretive study using diaries and semi-structured interviews with
      children and parents. Results from this research show that children recovering at
      home after surgery have increased dependency and are likely to become the centre
      of family life; re-establishing independence is a marker of recovery. When
      present, pain dominates the experience. The families that go home ill-prepared
      experience high levels of worry. In conclusion, recovery from surgery is
      influenced by multiple factors; overall, families and children are resilient.
      There is a role for health professionals to tailor and improve information
      provision to parents and children about post-operative recovery, including
      assessment and management of pain. Information should be made available that
      describes the experience of other families who have undergone a similar surgery,
      and families should be made aware of what information they need and how to access
      it before and after discharge.

PMID- 23118326
TI  - Clinical pharmacokinetics, metabolism, and drug-drug interaction of carfilzomib.
AB  - Carfilzomib, an irreversible proteasome inhibitor, has a favorable safety profile
      and significant antitumor activity in patients with relapsed and refractory
      multiple myeloma (MM). Here we summarize the clinical pharmacokinetics (PK),
      metabolism, and drug-drug interaction (DDI) profile of carfilzomib. The PK of
      carfilzomib, infused over 2-10 minutes, was evaluated in patients with solid
      tumors or MM. Metabolites of carfilzomib were characterized in patient plasma and
      urine samples. In vitro drug metabolism and DDI studies were conducted in human
      liver microsomes and hepatocytes. A clinical DDI study was conducted in patients
      with solid tumors to evaluate the effect of carfilzomib on CYP3A activity. Plasma
      concentrations of carfilzomib declined rapidly and in a biphasic manner after
      intravenous administration. The systemic half-life was short and the systemic
      clearance rate was higher than hepatic blood flow. Carfilzomib was cleared
      largely extrahepatically via peptidase cleavage and epoxide hydrolysis.
      Cytochrome P450-mediated metabolism played a minor role, suggesting that
      coadministration of P450 inhibitors or inducers is unlikely to change its PK
      profile. Carfilzomib showed direct and time-dependent inhibition of CYP3A in
      human liver microsome preparations and exposure to carfilzomib resulted in
      reductions in CYP3A and 1A2 gene expression in cultured human hepatocytes.
      However, administration of carfilzomib did not affect the PK of midazolam in
      patients with solid tumors, and there were no safety signals indicative of
      potential drug interactions. We conclude that the rapid systemic clearance and
      short half-life of carfilzomib limit clinically significant DDI.

PMID- 23118327
TI  - Impact of hydrolysis-mediated clearance on the pharmacokinetics of novel
      anaplastic lymphoma kinase inhibitors.
AB  - Compound 1 [(E)-4-fluoro-N-(6-((4-(2-hydroxypropan-2-yl)piperidin-1-yl)methyl)-1
      ((1S,4S)-4-(isopropylcarbamoyl)cyclohexyl)-1H-benzo[d]imidazol-2(3H)
      ylidene)benzamide], a new, potent, selective anaplastic lymphoma kinase (ALK)
      inhibitor with potential application for the treatment of cancer, was selected as
      candidate to advance into efficacy studies in mice. However, the compound
      underwent mouse-specific enzymatic hydrolysis in plasma to a primary amine
      product (M1). Subsequent i.v. pharmacokinetics studies in mice showed that
      compound 1 had high clearance (CL) and a short half-life. Oral dose escalation
      studies in mice indicated that elimination of compound 1 was saturable, with
      higher doses achieving sufficient exposures above in vitro IC(50). Chemistry
      efforts to minimize hydrolysis resulted in the discovery of several analogs that
      were stable in mouse plasma. Three were taken in vivo into mice and showed
      decreased CL corresponding to increased in vitro stability in plasma. However,
      the more stable compounds also showed reduced potency against ALK. Kinetic
      studies in NADPH-fortified and unfortified microsomes and plasma produced
      submicromolar K(m) values and could help explain the saturation of elimination
      observed in vivo. Predictions of CL based on kinetics from hydrolysis and NADPH
      dependent pathways produced predicted hepatic CL values of 3.8, 3.0, 1.6, and 1.2
      l/h?kg for compound 1, compound 2 [(E)-3,5-difluoro-N-(6-((4-(2-hydroxypropan-2
      yl)piperidin-1-yl)methyl)-1-((1s,4s)-4-(isopropylcarbamoyl)cyclohexyl)-1H
      benzo[d]imidazol-2(3H)-ylidene)benzamide], compound 3 [(E)-3-chloro-5-fluoro-N-(6
      ((4-(2-hydroxypropan-2-yl)piperidin-1-yl)methyl)-1-((1s,4s)-4
      (isopropylcarbamoyl)cyclohexyl)-1H-benzo[d]imidazol-2(3H)-ylidene)benzamide], and
      compound 4 [(E)-N-(6-((4-(2-hydroxypropan-2-yl)piperidin-1-yl)methyl)-1-((1s,4s)
      4-(isopropylcarbamoyl)cyclohexyl)-1H-benzo[d]imidazol-2(3H)-ylidene)-3
      (trifluoromethyl)benzamide], respectively. The in vivo observed CLs for compounds
      1, 2, 3, and 4 were 5.52, 3.51, 2.14, and 2.66 l/h?kg, respectively. These
      results indicate that in vitro metabolism kinetic data, incorporating
      contributions from both hydrolysis and NADPH-dependent metabolism, could be used
      to predict the systemic CL of compounds cleared via hydrolytic pathways provided
      that the in vitro assays thoroughly investigate the processes, including the
      contribution of other metabolic pathways and the possibility of saturation
      kinetics.

PMID- 23118328
TI  - Evaluation of the relationship between sex, polymorphisms in CYP2C8 and CYP2C9,
      and pharmacokinetics of angiotensin receptor blockers.
AB  - Angiotensin II receptor blockers (ARBs) are used to treat hypertension. Most ARBs
      are metabolized by CYP2C9. The aim of this study is to evaluate the possible
      association between sex, polymorphisms in the CYP2C8 and CYP2C9 genes, and the
      pharmacokinetics of losartan, valsartan, candesartan, and telmisartan. The study
      population comprised 246 healthy volunteers from seven single-dose clinical
      trials: 64 from two candesartan studies, 43 from a telmisartan study, 36 from a
      losartan study, and 103 from three valsartan studies. DNA was extracted from
      blood samples and single-nucleotide polymorphisms in the CYP2C8 (CYP2C8*2,
      CYP2C8*3, CYP2C8*4, CYP2C8*5) and CYP2C9 (CYP2C9*2, CYP2C9*3) genes were
      evaluated using real-time polymerase chain reaction. Sex only affected
      telmisartan pharmacokinetics, since women showed a higher telmisartan C(max) than
      men (590.5 +/- 75.8 ng/ml versus 282.1 +/- 30.8 ng/ml; P <= 0.01). CYP2C9
      variants were associated only with losartan pharmacokinetics: the half-life of
      losartan was higher in CYP2C9*3 allele carriers (3.1 +/- 0.4 hours) than in
      volunteers with the wild-type genotype (2.3 +/- 0.1 hours) (P <= 0.05). CYP2C8
      polymorphisms were associated only with valsartan pharmacokinetics, since *2
      allele carriers showed faster clearance (1.07 +/- 0.57 l/h.kg) than those with
      the wild-type genotype (0.48 +/- 0.72 l/h.kg; P <= 0.01) and carriers of the *3
      allele (0.35 +/- 0.49 l/h.kg; P <= 0.001). These results suggest that genotypes
      for CYP2C9 and CYP2C8 are relevant to the pharmacokinetics of losartan and
      valsartan, respectively, but not the pharmacokinetics of candesartan or
      telmisartan.

PMID- 23118330
TI  - Death of baby with anencephaly after mother was refused an abortion sparks
      controversy in India.

PMID- 23118331
TI  - Genetics testing firm is accused of "hiding vital breast cancer data".

PMID- 23118332
TI  - GSK backs BMJ's new policy to publish only studies with full access to data.

PMID- 23118333
TI  - Government drops plans to review the way women who are considering abortion are
      counselled.

PMID- 23118334
TI  - Payment by results system has outlived its usefulness, King's Fund report says.

PMID- 23118335
TI  - Exposing a chink in the armor of methicillin-resistant Staphylococcus aureus.

PMID- 23118336
TI  - Turning death into creative force during biofilm engineering.

PMID- 23118338
TI  - How HIV finds the door.

PMID- 23118337
TI  - Impact of pyrethroid resistance on operational malaria control in Malawi.
AB  - The impact of insecticide resistance on insect-borne disease programs is
      difficult to quantify. The possibility of eliminating malaria in high
      transmission settings is heavily dependent on effective vector control reducing
      disease transmission rates. Pyrethroids are the dominant insecticides used for
      malaria control, with few options for their replacement. Their failure will
      adversely affect our ability to control malaria. Pyrethroid resistance has been
      selected in Malawi over the last 3 y in the two major malaria vectors Anopheles
      gambiae and Anopheles funestus, with a higher frequency of resistance in the
      latter. The resistance in An. funestus is metabolically based and involves the up
      regulation of two duplicated P450s. The same genes confer resistance in
      Mozambican An. funestus, although the levels of up-regulation differ. The
      selection of resistance over 3 y has not increased malaria transmission, as
      judged by annual point prevalence surveys in 1- to 4-y-old children. This is true
      in areas with long-lasting insecticide-treated nets (LLINs) alone or LLINs plus
      pyrethroid-based insecticide residual spraying (IRS). However, in districts where
      IRS was scaled up, it did not produce the expected decrease in malaria
      prevalence. As resistance increases in frequency from this low initial level,
      there is the potential for vector population numbers to increase with a
      concomitant negative impact on control efficacy. This should be monitored
      carefully as part of the operational activities in country.

PMID- 23118339
TI  - Protein engineering methods applied to membrane protein targets.
AB  - Genes encoding membrane proteins have been estimated to comprise as much as 30%
      of the human genome. Among these membrane, proteins are a large number of
      signaling receptors, transporters, ion channels and enzymes that are vital to
      cellular regulation, metabolism and homeostasis. While many membrane proteins are
      considered high-priority targets for drug design, there is a dearth of structural
      and biochemical information on them. This lack of information stems from the
      inherent insolubility and instability of transmembrane domains, which prevents
      easy obtainment of high-resolution crystals to specifically study structure
      function relationships. In part, this lack of structures has greatly impeded our
      understanding in the field of membrane proteins. One method that can be used to
      enhance our understanding is directed evolution, a molecular biology method that
      mimics natural selection to engineer proteins that have specific phenotypes. It
      is a powerful technique that has considerable success with globular proteins,
      notably the engineering of protein therapeutics. With respect to transmembrane
      protein targets, this tool may be underutilized. Another powerful tool to
      investigate membrane protein structure-function relationships is computational
      modeling. This review will discuss these protein engineering methods and their
      tremendous potential in the study of membrane proteins.

PMID- 23118340
TI  - Development of an affinity-matured humanized anti-epidermal growth factor
      receptor antibody for cancer immunotherapy.
AB  - We showed previously that humanization of 528, a murine anti-epidermal growth
      factor receptor (EGFR) antibody, causes reduced affinity for its target. Here, to
      improve the affinity of the humanized antibody for use in cancer immunotherapy,
      we constructed phage display libraries focused on the complementarity-determining
      regions (CDRs) of the antibody and carried out affinity selection. Two-step
      selections using libraries constructed in a stepwise manner enabled a 32-fold
      affinity enhancement of humanized 528 (h528). Thermodynamic analysis of the
      interactions between the variable domain fragment of h528 (h528Fv) mutants and
      the soluble extracellular domain of EGFR indicated that the h528Fv mutants
      obtained from the first selection showed a large increase in negative enthalpy
      change due to binding, resulting in affinity enhancement. Furthermore, mutants
      from the second selection showed a decrease in entropy loss, which led to further
      affinity maturation. These results suggest that a single mutation in the heavy
      chain variable domain (i.e. Tyr(52) to Trp) enthalpically contributed for
      overcoming the energetic barrier to the antigen-antibody interaction, which was a
      major hurdle for the in vitro affinity maturation of h528. We reported previously
      that the humanized bispecific diabody hEx3 Db, which targets EGFR and CD3, shows
      strong anti-tumor activity. hEx3 Db mutants, in which the variable domains of
      h528 were replaced with those of the affinity-enhanced mutants, were prepared and
      characterized. In a growth inhibition assay of tumor cells, the hEx3 Db mutants
      showed stronger anti-tumor activity than that of hEx3 Db, suggesting that
      affinity enhancement of h528Fv enhances the anti-tumor activity of the bispecific
      diabody.

PMID- 23118341
TI  - Inhibition of peptidyl-arginine deiminases reverses protein-hypercitrullination
      and disease in mouse models of multiple sclerosis.
AB  - Multiple sclerosis (MS) is the most common CNS-demyelinating disease of humans,
      showing clinical and pathological heterogeneity and a general resistance to
      therapy. We first discovered that abnormal myelin hypercitrullination, even in
      normal-appearing white matter, by peptidylarginine deiminases (PADs) correlates
      strongly with disease severity and might have an important role in MS
      progression. Hypercitrullination is known to promote focal demyelination through
      reduced myelin compaction. Here we report that 2-chloroacetamidine (2CA), a small
      molecule, PAD active-site inhibitor, dramatically attenuates disease at any stage
      in independent neurodegenerative as well as autoimmune MS mouse models. 2CA
      reduced PAD activity and protein citrullination to pre-disease status. In the
      autoimmune models, disease induction uniformly induced spontaneous
      hypercitrullination with citrulline+ epitopes targeted frequently. 2CA rapidly
      suppressed T cell autoreactivity, clearing brain and spinal cord infiltrates,
      through selective removal of newly activated T cells. 2CA essentially prevented
      disease when administered before disease onset or before autoimmune induction,
      making hypercitrullination, and specifically PAD enzymes, a therapeutic target in
      MS models and thus possibly in MS.

PMID- 23118344
TI  - Complexity of molecular forms of B-type natriuretic peptide in heart failure.

PMID- 23118342
TI  - Muscleblind, BSF and TBPH are mislocalized in the muscle sarcomere of a
      Drosophila myotonic dystrophy model.
AB  - Myotonic dystrophy type 1 (DM1) is a genetic disease caused by the pathological
      expansion of a CTG trinucleotide repeat in the 3' UTR of the DMPK gene. In the
      DMPK transcripts, the CUG expansions sequester RNA-binding proteins into nuclear
      foci, including transcription factors and alternative splicing regulators such as
      MBNL1. MBNL1 sequestration has been associated with key features of DM1. However,
      the basis behind a number of molecular and histological alterations in DM1 remain
      unclear. To help identify new pathogenic components of the disease, we carried
      out a genetic screen using a Drosophila model of DM1 that expresses 480
      interrupted CTG repeats, i(CTG)480, and a collection of 1215 transgenic RNA
      interference (RNAi) fly lines. Of the 34 modifiers identified, two RNA-binding
      proteins, TBPH (homolog of human TAR DNA-binding protein 43 or TDP-43) and BSF
      (Bicoid stability factor; homolog of human LRPPRC), were of particular interest.
      These factors modified i(CTG)480 phenotypes in the fly eye and wing, and TBPH
      silencing also suppressed CTG-induced defects in the flight muscles. In
      Drosophila flight muscle, TBPH, BSF and the fly ortholog of MBNL1, Muscleblind
      (Mbl), were detected in sarcomeric bands. Expression of i(CTG)480 resulted in
      changes in the sarcomeric patterns of these proteins, which could be restored by
      coexpression with human MBNL1. Epistasis studies showed that Mbl silencing was
      sufficient to induce a subcellular redistribution of TBPH and BSF proteins in the
      muscle, which mimicked the effect of i(CTG)480 expression. These results provide
      the first description of TBPH and BSF as targets of Mbl-mediated CTG toxicity,
      and they suggest an important role of these proteins in DM1 muscle pathology.

PMID- 23118343
TI  - Endogenous ribosomal protein L29 (RPL29): a newly identified regulator of
      angiogenesis in mice.
AB  - Cellular ribosomal protein L29 (RPL29) is known to be important in protein
      synthesis, but its function during angiogenesis has never been described before.
      We have shown previously that mice lacking beta3-integrins support enhanced
      tumour angiogenesis and, therefore, deletion of endothelial alphavbeta3 can
      provide a method for discovery of novel regulators of tumour angiogenesis. Here,
      we describe significant upregulation of RPL29 in beta3-null endothelial cells at
      both the mRNA and protein level. Ex vivo, we show that VEGF-stimulated
      microvessel sprouting was reduced significantly in Rpl29-heterozygous and Rpl29
      null aortic ring assays compared with wild-type controls. Moreover, we provide in
      vivo evidence that RPL29 can regulate tumour angiogenesis. Tumour blood vessel
      density in subcutaneously grown Lewis lung carcinomas was reduced significantly
      in Rpl29-mutant mice. Additionally, depletion of Rpl29 using RNA interference
      inhibited VEGF-induced aortic ring sprouting, suggesting that anti-RPL29
      strategies might have anti-angiogenic potential. Overall, our results identify
      that loss or depletion of RPL29 can reduce angiogenesis in vivo and ex vivo.

PMID- 23118345
TI  - Prognostic value of cardiac troponin in chronic stable heart failure: a
      systematic review.
AB  - CONTEXT: Cardiac troponins have become the 'gold standard' for diagnosing
      myocardial infarction. Elevation of cardiac troponins is noted in patients with
      chronic stable heart failure, but comparative prognostic value of different assay
      types is not established. OBJECTIVE: To perform a systematic review for
      investigating the prognostic value of the different types of cardiac troponins
      (including low and high sensitivity) in chronic stable heart failure. DATA
      SOURCES: Search of three databases, PubMed, The Cochrane Library and Web of
      Science, was made in April 2012. STUDY SELECTION: All studies which provided
      information on prognosis based upon the baseline cardiac troponin elevation in
      chronic stable heart failure were included. Limits applied were adults, humans
      and English language. DATA EXTRACTION: Two authors individually reviewed all
      studies and extracted data on patient and study characteristics along with
      primary and secondary outcomes. RESULTS: 16 of the 365 papers from three
      databases were finally included for data analysis. Elevated baseline cardiac
      troponin in patients with chronic stable heart failure was associated with a high
      risk of mortality (HR 2.85; 95% CI 2.02 to 4.03) and combined adverse
      cardiovascular outcome (HR 2.38; 95% CI 1.63 to 3.49). Although high-sensitivity
      assay detected cardiac troponin in higher proportion of patients compared with
      low-sensitivity assay, there was no statistically significant difference among
      both groups (p=0.54). CONCLUSIONS: Elevated baseline cardiac troponin level
      identified chronic stable heart failure patients who are at a higher risk of
      mortality and combined adverse cardiovascular outcomes. There was no
      statistically significant difference between high- and low-sensitivity cardiac
      troponins.

PMID- 23118346
TI  - Clinical and intravascular imaging outcomes at 1 and 2 years after implantation
      of absorb everolimus eluting bioresorbable vascular scaffolds in small vessels.
      Late lumen enlargement: does bioresorption matter with small vessel size? Insight
      from the ABSORB cohort B trial.
AB  - BACKGROUND: The long-term results after second generation everolimus eluting
      bioresorbable vascular scaffold (Absorb BVS) placement in small vessels are
      unknown. Therefore, we investigated the impact of vessel size on long-term
      outcomes, after Absorb BVS implantation. METHODS: In ABSORB Cohort B Trial, out
      of the total study population (101 patients), 45 patients were assigned to
      undergo 6-month and 2-year angiographic follow-up (Cohort B1) and 56 patients to
      have angiographic follow-up at 1-year (Cohort B2). The pre-reference vessel
      diameter (RVD) was <2.5 mm (small-vessel group) in 41 patients (41 lesions) and
      >=2.5 mm (large-vessel group) in 60 patients (61 lesions). Outcomes were compared
      according to pre-RVD. RESULTS: At 2-year angiographic follow-up no differences in
      late lumen loss (0.29+/-0.16 mm vs 0.25+/-0.22 mm, p=0.4391), and in-segment
      binary restenosis (5.3% vs 5.3% p=1.0000) were demonstrated between groups. In
      the small-vessel group, intravascular ultrasound analysis showed a significant
      increase in vessel area (12.25+/-3.47 mm(2) vs 13.09+/-3.38 mm(2) p=0.0015),
      scaffold area (5.76+/-0.96 mm(2) vs 6.41+/-1.30 mm(2) p=0.0008) and lumen area
      (5.71+/-0.98 mm(2) vs 6.20+/-1.27 mm(2) p=0.0155) between 6-months and 2-year
      follow-up. No differences in plaque composition were reported between groups at
      either time point. At 2-year clinical follow-up, no differences in ischaemia
      driven major adverse cardiac events (7.3% vs 10.2%, p=0.7335), myocardial
      infarction (4.9% vs 1.7%, p=0.5662) or ischaemia-driven target lesion
      revascularisation (2.4% vs 8.5%, p=0.3962) were reported between small and large
      vessels. No deaths or scaffold thrombosis were observed. CONCLUSIONS: Similar
      clinical and angiographic outcomes at 2-year follow-up were reported in small and
      large vessel groups. A significant late lumen enlargement and positive vessel
      remodelling were observed in small vessels.

PMID- 23118347
TI  - Effect of amlodipine on platelet inhibition by clopidogrel in patients with
      ischaemic heart disease: a randomised, controlled trial.
AB  - BACKGROUND: Amlodipine inhibits cytochrome P450 (CYP) enzyme and has the
      potential to reduce clopidogrel bioactivation in vivo. Reports in previous
      retrospective studies described greater platelet reactivity in patients on
      amlodipine. OBJECTIVE: To evaluate the treatment effect of clopidogrel in
      patients on amlodipine versus not on calcium-channel blockers (CCBs). DESIGN AND
      SETTING: Randomised, controlled, open-label trial conducted in a regional acute
      hospital. PATIENTS AND INTERVENTIONS: 98 patients on clopidogrel for ischaemic
      heart disease were recruited consecutively and randomised to take either
      amlodipine or drugs with inert CYP effects as controls. The P2Y12 reaction unit
      (PRU) was measured using whole blood obtained at baseline and on day 28. MAIN
      OUTCOME MEASURES: The primary analysis involved the PRU values on day 28. The
      secondary analyses were percentage of platelet inhibition and poor response to
      clopidogrel as defined by PRU>235. RESULTS: Both groups experienced comparable
      day 28 PRUs (amlodipine 227+/-84 vs control 214+/-90; mean difference 12.7, 95%
      CI -22 to +47). Percentage of platelet inhibition (amlodipine 33% vs control 38%,
      mean difference -4.5%, 95% CI -14% to +5%) and those with poor response on day 28
      (amlodipine 49% vs control 45%; p=0.76) did not differ significantly.
      CONCLUSIONS: Concomitant amlodipine has no negative impact on clopidogrel
      mediated platelet inhibition in patients with ischaemic heart disease.

PMID- 23118348
TI  - Predictors of outcome in 176 South African patients with peripartum
      cardiomyopathy.
AB  - OBJECTIVE: Identify novel prognostic factors for patients with peripartum
      cardiomyopathy (PPCM). DESIGN AND SETTING: Prospective cohort study conducted in
      a single tertiary care centre in South Africa. PATIENTS: 176 African women with
      newly diagnosed PPCM were studied. INTERVENTIONS: Clinical assessment,
      echocardiography and laboratory results were obtained at baseline and at 6
      months. MAIN OUTCOME MEASURES: Poor outcome was defined as the combined end point
      of death, left ventricular (LV) ejection fraction (LVEF) < 35%, or remaining in
      New York Heart Association (NYHA) functional class III/IV at 6 months. Complete
      LV recovery was defined as LVEF >=55% at 6 months. RESULTS: Forty-five (26%)
      patients had a poor outcome. Multiple logistic regression analysis revealed that,
      after adjustment for age, NYHA functional class, LVEF and systolic blood
      pressure, increased left ventricular end systolic dimension (LVESD), lower body
      mass index (BMI) and lower total cholesterol at baseline were independent
      predictors of poor outcome (adjusted OR 1.09, 95% CI 1.04 to 1.15, p=0.001; OR
      0.89, 95% CI 0.83 to 0.96, p=0.004, and OR 0.50, 95% CI 0.34 to 0.73, p=0.0004,
      respectively). Thirty (21%) of the 141 surviving patients with echocardiographic
      follow-up recovered LV function at 6 months. Multiple logistic regression
      analysis revealed that, after adjustment for NYHA functional class, LVEF and left
      ventricular end diastolic dimension, older age and smaller LVESD at baseline were
      predictors of LV recovery (OR 1.08, 95% CI 1.01 to 1.17, p=0.02 and OR 0.92, 95%
      CI 0.86 to 0.98, p=0.007, respectively). CONCLUSIONS: This study suggests that
      increased LVESD, lower BMI and lower serum cholesterol at baseline may be
      independent predictors of poor outcome in patients with PPCM, while older age and
      smaller LVESD at baseline appear to be independently associated with a higher
      chance of LV recovery.

PMID- 23118349
TI  - Arterial disease in chronic kidney disease.
AB  - End stage renal disease is associated with a very high risk of premature
      cardiovascular death and morbidity. Early stage chronic kidney disease (CKD) is
      also associated with an increased frequency of cardiovascular events and is a
      common but poorly recognised and undertreated risk factor. Cardiovascular disease
      in CKD can be attributed to two distinct but overlapping pathological processes,
      namely atherosclerosis and arteriosclerosis. While the risk of athero-thrombotic
      events such as myocardial infarction is elevated, arteriosclerosis is the
      predominant pathophysiological process involving fibrosis and thickening of the
      medial arterial layer. This results in increased arterial stiffness causing left
      ventricular hypertrophy and fibrosis and the exposure of vulnerable vascular beds
      such as the brain and kidney to high pressure fluctuations causing small vessel
      disease. These pathophysiological features are manifest by a high risk of lethal
      arrhythmia, congestive heart failure, myocardial infarction and stroke. Recent
      work has highlighted the importance of aldosterone and disordered bone mineral
      metabolism.

PMID- 23118350
TI  - Kidins220 accumulates with tau in human Alzheimer's disease and related models:
      modulation of its calpain-processing by GSK3beta/PP1 imbalance.
AB  - Failures in neurotrophic support and signalling play key roles in Alzheimer's
      disease (AD) pathogenesis. We previously demonstrated that downregulation of the
      neurotrophin effector Kinase D interacting substrate (Kidins220) by
      excitotoxicity and cerebral ischaemia contributed to neuronal death. This
      downregulation, triggered through overactivation of N-methyl-D-aspartate
      receptors (NMDARs), involved proteolysis of Kidins220 by calpain and
      transcriptional inhibition. As excitotoxicity is at the basis of AD aetiology, we
      hypothesized that Kidins220 might also be downregulated in this disease.
      Unexpectedly, Kidins220 is augmented in necropsies from AD patients where it
      accumulates with hyperphosphorylated tau. This increase correlates with enhanced
      Kidins220 resistance to calpain processing but no higher gene transcription.
      Using AD brain necropsies, glycogen synthase kinase 3-beta (GSK3beta)-transgenic
      mice and cell models of AD-related neurodegeneration, we show that GSK3beta
      phosphorylation decreases Kidins220 susceptibility to calpain proteolysis, while
      protein phosphatase 1 (PP1) action has the opposite effect. As altered activities
      of GSK3beta and phosphatases are involved in tau aggregation and constitute
      hallmarks in AD, a GSK3beta/PP1 imbalance may also contribute to Kidins220
      decreased clearance, accumulation and hampered neurotrophin signalling from early
      stages of the disease pathogenesis. These results encourage searches for
      mutations in Kidins220 gene and their possible associations to dementias.
      Finally, our data support a model where the effects of excitotoxicity drastically
      differ when occurring in cerebral ischaemia versus progressively sustained
      toxicity along AD progression. The striking differences in Kidins220 stability
      resulting from chronic versus acute brain damage may also have important
      implications for the therapeutic intervention of neurodegenerative disorders.

PMID- 23118351
TI  - Neuronopathic Gaucher's disease: induced pluripotent stem cells for disease
      modelling and testing chaperone activity of small compounds.
AB  - Gaucher's disease (GD) is caused by mutations in the GBA1 gene, which encodes
      acid-beta-glucosidase, an enzyme involved in the degradation of complex
      sphingolipids. While the non-neuronopathic aspects of the disease can be treated
      with enzyme replacement therapy (ERT), the early-onset neuronopathic form
      currently lacks therapeutic options and is lethal. We have developed an induced
      pluripotent stem cell (iPSc) model of neuronopathic GD. Dermal fibroblasts of a
      patient with a P.[LEU444PRO];[GLY202ARG] genotype were transfected with a loxP
      flanked polycistronic reprogramming cassette consisting of Oct4, Sox2, Klf4 and c
      Myc and iPSc lines derived. A non-integrative lentiviral vector expressing Cre
      recombinase was used to eliminate the reprogramming cassette from the
      reprogrammed cells. Our GD iPSc express pluripotent markers, differentiate into
      the three germ layers, form teratomas, have a normal karyotype and show the same
      mutations and low acid-beta-glucosidase activity as the original fibroblasts they
      were derived from. We have differentiated them efficiently into neurons and also
      into macrophages without observing deleterious effects of the mutations on the
      differentiation process. Using our system as a platform to test chemical
      compounds capable of increasing acid-beta-glucosidase activity, we confirm that
      two nojirimycin analogues can rescue protein levels and enzyme activity in the
      cells affected by the disease.

PMID- 23118354
TI  - The best laid plans: analyzing courtship defects in Drosophila.
AB  - Courtship can be defined as behavioral interactions between males and females,
      the evolutionary objective of which is copulation and the ultimate perpetuation
      of the species. This protocol allows determination of two aspects of courtship in
      Drosophila: to assess whether there is a deficiency in mating frequency and, if
      this is the case, to resolve the nature of the specific problem. The first part
      of the approach provides a simple, objective, high-throughput strategy that is
      ideal for determining whether a specific strain has any courtship defect. Any
      strain that mates at a frequency comparable to that of wild-type flies must be
      considered reasonably fit in an evolutionary sense. If a specific strain has an
      abnormal mating frequency, we are then interested in determining whether there is
      a specific courtship defect, as described in the second half of the protocol.
      This requires direct live observation or digital recording of courtship.

PMID- 23118352
TI  - The molecular function and clinical phenotype of partial deletions of the
      IGF2/H19 imprinting control region depends on the spatial arrangement of the
      remaining CTCF-binding sites.
AB  - At chromosome 11p15.5, the imprinting centre 1 (IC1) controls the parent of
      origin-specific expression of the IGF2 and H19 genes. The 5 kb IC1 region
      contains multiple target sites (CTS) for the zinc-finger protein CTCF, whose
      binding on the maternal chromosome prevents the activation of IGF2 and allows
      that of H19 by common enhancers. CTCF binding helps maintaining the maternal IC1
      methylation-free, whereas on the paternal chromosome gamete-inherited DNA
      methylation inhibits CTCF interaction and enhancer-blocking activity resulting in
      IGF2 activation and H19 silencing. Maternally inherited 1.4-2.2 kb deletions are
      associated with methylation of the residual CTSs and Beckwith-Wiedemann syndrome,
      although with different penetrance and expressivity. We explored the relationship
      between IC1 microdeletions and phenotype by analysing a number of previously
      described and novel mutant alleles. We used a highly quantitative assay based on
      next generation sequencing to measure DNA methylation in affected families and
      analysed enhancer-blocking activity and CTCF binding in cultured cells. We
      demonstrate that the microdeletions mostly affect IC1 function and CTCF binding
      by changing CTS spacing. Thus, the extent of IC1 inactivation and the clinical
      phenotype are influenced by the arrangement of the residual CTSs. A CTS spacing
      similar to the wild-type allele results in moderate IC1 inactivation and is
      associated with stochastic DNA methylation of the maternal IC1 and incomplete
      penetrance. Microdeletions with different CTS spacing display severe IC1
      inactivation and are associated with IC1 hypermethylation and complete
      penetrance. Careful characterization of the IC1 microdeletions is therefore
      needed to predict recurrence risks and phenotypical outcomes.

PMID- 23118353
TI  - Protein disulfide isomerase in ALS mouse glia links protein misfolding with NADPH
      oxidase-catalyzed superoxide production.
AB  - Protein disulfide isomerase (PDI) is an oxidoreductase assisting oxidative
      protein folding in the endoplasmic reticulum of all types of cells, including
      neurons and glia. In neurodegenerative disorders, such as amyotrophic lateral
      sclerosis (ALS), up-regulation of PDI is an important part of unfolded protein
      response (UPR) that is thought to represent an adaption reaction and thereby
      protect the neurons. Importantly, studies on animal models of familial ALS with
      mutant Cu/Zn superoxide dismutase 1 (SOD1) have shown that the mutant SOD1 in
      astrocytes or microglia strongly regulates the progression of the disease. Here,
      we found an early up-regulation of PDI in microglia of transgenic (tg) mutant
      SOD1 mice, indicating that in addition to neurons, UPR takes place in glial cells
      in ALS. The observation was supported by the finding that also the expression of
      a UPR marker GADD34 (growth arrest and DNA damage-inducible protein) was induced
      in the spinal cord glia of tg mutant SOD1 mice. Because mutant SOD1 can cause
      sustained activation of NADPH oxidase (NOX), we investigated the role of PDI in
      UPR-induced NOX activation in microglia. In BV-2 microglia, UPR resulted in NOX
      activation with increased production of superoxide and increased release of tumor
      necrosis factor-alpha. The phenomenon was recapitulated in primary rat microglia,
      murine macrophages and human monocytes. Importantly, pharmacological inhibition
      of PDI or its down-regulation by short interfering RNAs prevented NOX activation
      in microglia and subsequent production of superoxide. Thus, results strongly
      demonstrate that UPR, caused by protein misfolding, may lead to PDI-dependent NOX
      activation and contribute to neurotoxicity in neurodegenerative diseases
      including ALS.

PMID- 23118356
TI  - Data analysis considerations for detecting copy number changes in formalin-fixed,
      paraffin-embedded tissues.
AB  - The Whole Genome Sampling Analysis (WGSA) assay in combination with Affymetrix
      GeneChip Mapping Arrays is used for copy number analysis of high-quality DNA
      samples (i.e., samples that have been collected from blood, fresh or frozen
      tissue, or cell lines). Formalin-fixed, paraffin-embedded (FFPE) samples,
      however, represent the most prevalent form of archived clinical samples, but they
      provide additional challenges for molecular assays. FFPE processing usually
      results in the degradation of FFPE DNA and in the contamination and chemical
      modification of these DNA samples. In this article, we describe the steps needed
      to obtain reliable copy number predictions from degraded and contaminated FFPE
      samples.

PMID- 23118355
TI  - Sample processing considerations for detecting copy number changes in formalin
      fixed, paraffin-embedded tissues.
AB  - The Whole Genome Sampling Analysis (WGSA) assay in combination with Affymetrix
      GeneChip Mapping Arrays is used for copy number analysis of high-quality DNA
      samples (i.e., samples that have been collected from blood, fresh or frozen
      tissue, or cell lines). Formalin-fixed, paraffin-embedded (FFPE) samples,
      however, represent the most prevalent form of archived clinical samples, but they
      provide additional challenges for molecular assays. FFPE processing usually
      results in the degradation of FFPE DNA and in the contamination and chemical
      modification of these DNA samples. Because of these issues, FFPE DNA is not
      suitable for all molecular assays designed for high-quality DNA samples.
      Strategies recommended for processing FFPE DNA samples through WGSA and to the
      Mapping arrays are described here.

PMID- 23118357
TI  - Estimating volume in biological structures.
AB  - Estimates of volume can be useful in comparative and experimental studies of
      tissues and organs. In this article, a simple procedure for making unbiased
      estimates of total volume using Cavalieri's principle is described. This is
      followed by a description of how point probes can be used to make unbiased
      estimates of the areas of sectional profiles and how, when combined with
      Cavalieri's principle, point counting can be used to make an unbiased estimate of
      the volume of a structural feature.

PMID- 23118358
TI  - Objective-type total internal reflection microscopy (excitation) for single
      molecule FRET.
AB  - Single-molecule (sm) fluorescence detection is a powerful method for studying
      biological events without time and population averaging. Forster (fluorescence)
      resonance energy transfer (FRET) is a spectroscopic technique in which the
      efficiency of energy transfer from donor to acceptor molecules is used to
      determine distances between molecules in the 30-80 A range. Structural changes in
      biological molecules or relative motion between two interacting molecules can be
      detected by a change in FRET. A variant of smFRET is based on total internal
      reflection (TIR) microscopy, which can be set up in two ways, either using an oil
      immersion (objective-type) or a water-immersion (prism-type) lens. This protocol
      describes objective-type TIR microscopy (excitation), including setup of the
      laser beam and epifluorescence microscopy, and conversion of the latter into TIR.

PMID- 23118359
TI  - Objective-type total internal reflection microscopy (emission) for single
      molecule FRET.
AB  - Single-molecule (sm) fluorescence detection is a powerful method for studying
      biological events without time and population averaging. Forster (fluorescence)
      resonance energy transfer (FRET) is a spectroscopic technique in which the
      efficiency of energy transfer from donor to acceptor molecules is used to
      determine distances between molecules in the 30-80 A range. Structural changes in
      biological molecules or relative motion between two interacting molecules can be
      detected by a change in FRET. A variant of smFRET is based on total internal
      reflection (TIR) microscopy, which can be set up in two ways, either using an oil
      immersion (objective-type) or a water-immersion (prism-type) lens. This protocol
      describes the preparation of a fluorescent bead sample and the setup for
      objective-type TIR microscopy (emission).

PMID- 23118360
TI  - In vitro transcription of labeled RNA: synthesis, capping, and substitution.
AB  - All in vitro RNA transcription reactions involve the use of common components: a
      template, phage RNA polymerase, and ribonucleoside triphosphates (rNTPs). The
      concentration of rNTPs is a crucial variable that is manipulated to determine the
      specific activities of labeled RNAs. This protocol describes methods used to
      synthesize RNAs of low specific activity (trace labeled), medium specific
      activity, and high specific activity. Also described is how the same principles
      that determine the level of incorporation of labeled rNTPs are applicable to the
      synthesis of transcripts containing modified nucleotides, including 5' cap and
      internal (body) modifications such as biotinylated uridine, 4-thiouridine, and
      phosphorothiotated nucleotides. Careful attention to detail in setting up the
      transcription reaction will permit the synthesis of any number of "designer
      RNAs."

PMID- 23118361
TI  - Two-photon sodium imaging in dendritic spines.
AB  - Neuronal activity causes substantial postsynaptic Na(+) transients. However, the
      physiological consequences of such Na(+) transients remain largely unknown. High
      resolution Na(+) imaging is pivotal to study these questions, and, up to now, two
      photon imaging with the fluorescent Na(+) indicator sodium-binding benzofuran
      isophthalate (SBFI) has been the method of choice. When introduced into
      individual neurons in acute tissue slices, SBFI enables measurements of
      [Na(+)](i) transients in dendrites and spines. This technique is also suitable
      for the determination of [Na(+)](i) transients in other cell types, such as glial
      cells, with high spatial resolution, and is likely to be useful for measurement
      of Na(+) signals in vivo. This protocol provides guidelines and tips for
      measuring dynamic Na(+) concentrations within neurons, as well as an in situ
      calibration procedure. Because the basic properties of SBFI inside a cell differ
      significantly from the same properties in vitro, in situ calibrations are
      required to obtain meaningful experimental results.

PMID- 23118362
TI  - In vivo imaging of the developing neuromuscular junction in neonatal mice.
AB  - Although fluorescently labeled structures can be analyzed more easily at high
      resolution in fixed-tissue preparations than in living animals, some biological
      questions can only be answered by time-lapse imaging. Changes in nervous system
      wiring during development cannot be determined reliably by taking tissue from
      different animals at staggered time points. Rather, the same cells and
      connections must be viewed repeatedly. To study developmental synapse
      elimination, we image muscles in transgenic mice that express fluorescent
      proteins in motor neurons and follow the same neuromuscular junctions (NMJs) over
      multiple days. This protocol describes the use of confocal microscopy for in vivo
      imaging of developing NMJs in transgenic neonatal mice expressing cyan
      fluorescent protein (CFP) or yellow fluorescent protein (YFP). The sternomastoid,
      a flat, accessible neck muscle with large junctions, is imaged. A principal
      advantage of confocal microscopy is the ability to acquire multiple fluorescence
      channels simultaneously. If the channels are acquired sequentially, there is
      inevitably misalignment because of movement. Moreover, the total imaging time
      scales linearly with the number of channels. With simultaneous acquisition, only
      a single scan may be required. With perfect alignment between channels,
      irrespective of movement that might occur during a scan, color differences can be
      used to study interactions between axons over time. A limitation of this
      technique is that axons must be brightly labeled and at the muscle surface. NMJs
      that are more than one muscle fiber deep may be difficult to scan because of
      index of refraction changes that cause image blurring.

PMID- 23118363
TI  - Imaging intracellular signaling using two-photon fluorescent lifetime imaging
      microscopy.
AB  - The recent development of Forster resonance energy transfer (FRET) sensors and
      FRET imaging techniques permits visualization of the dynamics of intracellular
      signaling events with high spatiotemporal resolution. In particular, fluorescence
      lifetime imaging in combination with two-photon laser-scanning microscopy (two
      photon fluorescence lifetime imaging microscopy [2pFLIM]) is a powerful tool to
      monitor signaling events in small subcellular compartments in thick tissue. This
      article provides practical guidelines for quantitative imaging of intracellular
      signaling using 2pFLIM.

PMID- 23118364
TI  - Lymphangiography of the mouse tail.
AB  - The lymphatic system is an important route for metastasis of cancer cells.
      Lymphatic microvessels have been studied by adapting lymphangiography to the
      mouse tail. In this technique, a high-molecular-weight fluorescently labeled
      tracer is injected into the interstitial compartment of the tail tissue. The
      tracer migrates to the local lymphatic vessels and fills the network, allowing
      visualization. By implanting a tumor in the tail, the structure and function of
      the lymphatics at the tumor periphery can be monitored. This protocol describes a
      method for injecting tumor cells into a mouse tail and for microlymphangiography.

PMID- 23118365
TI  - Lymphangiography of the mouse ear.
AB  - The lymphatic system is an important route for metastasis of cancer cells.
      Lymphatic microvessels have been studied by adapting lymphangiography to the
      mouse ear. In this technique, a high-molecular-weight fluorescently labeled
      tracer is injected into the interstitial compartment of the ear chamber. The
      tracer migrates to the local lymphatic vessels and fills the network, allowing
      visualization. Lymphangiography with Evan's blue dye or fluorescein
      isothiocyanate (FITC)-dextran reveals a dense auricular network of lymphatic
      capillaries, draining to a larger vessel at the ear base and subsequently to the
      exposed superficial cervical lymph node.

PMID- 23118366
TI  - Removing rRNA from deproteinized, phenol-extracted total RNA by enzymatic
      digestion.
AB  - Ribosomal RNAs (28S, 18S, 5.8S, and 5S rRNAs) comprise the vast majority of total
      cellular RNAs (>95%). When other RNAs are to be analyzed, it is very advantageous
      to remove the rRNA species. The best way to eliminate rRNA "contamination" is to
      pellet subunits before deproteinization. When this is not possible, certain RNAs
      can be separated from bulk rRNA after extraction. This protocol describes
      enzymatic digestion to remove rRNAs from deproteinized, phenol-extracted total
      RNA.

PMID- 23118367
TI  - CLIP (cross-linking and immunoprecipitation) identification of RNAs bound by a
      specific protein.
AB  - Guilt by association remains a powerful argument for assigning function in
      biological processes: Proteins that bind a specific RNA are strongly implicated
      in modulating the fate and action of that RNA. Detecting such associations is a
      major goal in understanding RNA function. The cross-linking and
      immunoprecipitation (CLIP) method described here allows assignments of RNA
      binding proteins to their RNA targets by using ultraviolet (UV) cross-linking to
      covalently capture close (near-covalent bond distances) association of RNA with
      protein, followed by immunopurification of the protein partner with extraction
      and subsequent characterization of the RNA partner sequence(s). Pools of target
      sequences can be captured and their genomic origins are studied so that
      regulatory and other functional relationships between the protein and its RNA
      targets can be inferred. The advantage of this protocol is that it captures only
      intimately associated RNAs and proteins, and so is expected to be highly
      specific. Some investigators report capturing cross-links between rRNA and
      nonribosomal proteins in cases where ribosomes are not efficiently cleared from
      the lysate before immunopurification of the target protein, so the limits of
      specificity for the method are yet to be fully explored. Its main disadvantages
      are its many steps and that it may fail to work for all proteins or capture all
      legitimate targets of any given protein if the necessary chemical groups are not
      optimally arranged for photocross-linking in the complex. However, properly
      performed, this method should provide many useful insights into the nature of the
      RNA ligands for an RNA-binding protein of interest.

PMID- 23118368
TI  - Managing depression in countries with low and middle incomes: an imperative for
      human immunodeficiency virus/acquired immune deficiency syndrome care and
      treatment and general public health.

PMID- 23118369
TI  - Dawn of a new day.

PMID- 23118370
TI  - Current guidelines for total joint VTE prophylaxis: dawn of a new day.
AB  - Venous thromboembolism (VTE) remains an immediate   threat to patients following
      total hip and knee replacement. While   there is a strong consensus that steps
      should be taken to minimise   the risk to patients by utilising some forms of
      prophylaxis for   the vast majority of patients, the methods utilised have been
      extremely   variable. Clinical practice guidelines (CPGs) have been published  
      by various professional organisations for over 25 years to provide
      recommendations   to standardise VTE prophylaxis. Historically, these
      recommendations   have varied widely depending in underlying assumptions, goals,
      and   methodology of the various groups. This effort has previously been  
      exemplified by the American College of Chest Physicians (ACCP) and   the American
      Academy of Orthopaedic Surgeons (AAOS). The former   group of medical specialists
      targeted minimising venographically   proven deep vein thrombosis (DVT) (the vast
      majority of which are   asymptomatic) as their primary goal prior to 2012. The
      latter group of   surgeons targeted minimising symptomatic VTE. As a result prior
      to 2012, the recommendations of the two groups were widely divergent.   In the
      past year, both groups have reassessed the current literature   with the
      principal goals of minimising symptomatic VTE events and   bleeding
      complications. As a result, for the first time the CPGs   of these two major
      subspecialty organisations are in close agreement.

PMID- 23118371
TI  - Minimising blood loss and transfusion in contemporary hip and knee arthroplasty.
AB  - Despite advances in contemporary hip and knee   arthroplasty, blood loss
      continues to be an issue. Though blood transfusion   has long been used to treat
      post-operative anemia, the associated   risks are well established. The objective
      of this article is to   present two practical and effective approaches to
      minimising blood   loss and transfusion rates in hip and knee arthroplasty: the
      use   of antifibrinolytic medications such as tranexamic acid and the   adoption
      of more conservative transfusion indications.

PMID- 23118372
TI  - If hip implant retrievals could speak, what would they tell us?
AB  - Hip implant retrieval analysis is the most important   source of insight into the
      performance of new materials and designs   of hip arthroplasties. Even the most
      rigorous in vitro testing will   not accurately simulate the behavior of implant
      materials and new   designs of prosthetic arthroplasties. Retrieval analysis has
      revealed   such factors as the effects of gamma-in-air sterilisation of
      polyethylene,   fatigue failure mechanisms of polymethylmethacrylate bone cement,
      fretting corrosion of Morse taper junctions, third body wear effects   of both
      hard-on-hard and hard-on-soft bearing couples, and the effects   of impingement
      of components on the full spectrum of bearing surfaces,   none of which was
      predicted by pre-implantation in vitro testing   of these materials and
      combinations. The temporal sequence of the   retrieval process is approximately
      six years from first implantation   through retrieval analysis, laboratory
      investigation, and publication   of results, and thus, in addition to rigorous
      clinical evaluation,   represents the true development and insight cycle for new
      designs   and materials.

PMID- 23118373
TI  - The Hip Society: algorithmic approach to diagnosis and management of metal-on
      metal arthroplasty.
AB  - Since 1996 more than one million metal-on-metal   articulations have been
      implanted worldwide. Adverse reactions to   metal debris are escalating. Here we
      present an algorithmic approach   to patient management. The general approach to
      all arthroplasty   patients returning for follow-up begins with a detailed
      history,   querying for pain, discomfort or compromise of function. Symptomatic  
      patients should be evaluated for intra-articular and extra-articular   causes of
      pain. In large head MoM arthroplasty, aseptic loosening   may be the source of
      pain and is frequently difficult to diagnose.   Sepsis should be ruled out as a
      source of pain. Plain radiographs   are evaluated to rule out loosening and
      osteolysis, and assess component   position. Laboratory evaluation commences with
      erythrocyte sedimentation   rate and C-reactive protein, which may be elevated.
      Serum metal   ions should be assessed by an approved facility. Aspiration, with  
      manual cell count and culture/sensitivity should be performed, with   cloudy to
      creamy fluid with predominance of monocytes often indicative   of failure.
      Imaging should include ultrasound or metal artifact   reduction sequence MRI,
      specifically evaluating for fluid collections   and/or masses about the hip. If
      adverse reaction to metal debris   is suspected then revision to metal or ceramic
      on-polyethylene is indicated   and can be successful. Delay may be associated
      with extensive soft-tissue   damage and hence poor clinical outcome.

PMID- 23118374
TI  - Subcapital fractures: a changing paradigm.
AB  - Options for the treatment of subcapital femoral   neck fractures basically fall
      into two categories: internal fixation   or arthroplasty (either hemiarthroplasty
      or total hip arthroplasty).   Historically, the treatment option has been driven
      by a diagnosis-related approach   (non-displaced neck fractures versus displaced
      neck fractures).   More recently, the traditional paradigm has changed. Instead
      of   a diagnosis-related approach, it has become more of a patient-related  
      approach. Treatment options take in to consideration the patient's age,  
      functional demands, and individual risk profile. A simple algorithm   can be
      helpful in terms of directing the treatment. Non-displaced   fractures,
      regardless of age of the patient, should be treated with   closed reduction and
      internal fixation. For displaced femoral neck fractures,   the treatment differs
      depending on the age of the patient. The younger   patient should be treated with
      urgent ORIF with the goal of an anatomic   reduction. For displaced femoral neck
      fractures in the elderly,   cognitive function should be determined. For those
      who are cognitively   functioning, total hip arthroplasty appears to be the best
      option.   In the cognitively dysfunctional, a bipolar hemiarthroplasty or   a
      total hip arthroplasty with use of larger heads (32 mm or 36 mm)   and/or
      constrained sockets are a viable option.

PMID- 23118375
TI  - Metastatic disease around the hip: maintaining quality of life.
AB  - Many tumors metastasise to bone, therefore, pathologic   fracture and impending
      pathologic fractures are common reasons for   orthopedic consultation. Having
      effective treatment strategies is   important to avoid complications, and relieve
      pain and preserve   function. Thorough pre-operative evaluation is recommended
      for medical   optimization and to ensure that the lesion is in fact a metastasis 
      and not a primary bone malignancy. For impending fractures, various scoring  
      systems have been proposed to determine the risk of fracture, and   therefore the
      need for prophylactic stabilisation. Lower score lesions   can often be treated
      with radiation, while more problematic lesions   may require internal fixation.
      Intramedullary fixation is generally   preferred due to favorable biomechanics.
      Arthroplasty may be required   for lesions with massive bony destruction where
      internal fixation   attempts are likely to fail. Radiation may also be useful
      postoperatively   to minimise construct failure due to tumor progression.

PMID- 23118376
TI  - Intra-operative fractures during THA: see it before it sees us.
AB  - The purpose of this paper is to discuss the risk   factors, prevention
      strategies, classification, and treatment of   intra-operative femur fractures
      sustained during primary and revision   total hip arthroplasty.

PMID- 23118377
TI  - Femoroacetabular impingement: a resurfacing solution.
AB  - Femoroacetabular impingement (FAI) is commonly   associated with early hip
      arthritis. We reviewed our series of 1300   hip resurfacing procedures. More than
      90% of our male patients,   with an average age of 53 years, had cam impingement
      lesions. In   this condition, there are anterior femoral neck osteophytes, and  
      a retroverted femoral head on a normally anteverted neck. It is   postulated that
      FAI results in collision of the anterior neck of   the femur against the rim of
      the acetabulum, causing damage to the   acetabular labrum and articular
      cartilage, resulting in osteoarthritis.   Early treatment of FAI involves
      arthroscopic or open removal of   bone from the anterior femoral neck, as well as
      repair or removal   of labral tears. However, once osteoarthritis has developed,
      hip   replacement or hip resurfacing is indicated. Hip resurfacing can   re
      orient the head and re-shape the neck. This helps to restore   normal
      biomechanics to the hip, eliminate FAI, and improve range   of motion. Since many
      younger men with hip arthritis have FAI, and   are also considered the best
      candidates for hip resurfacing, it   is evident that resurfacing has a role in
      these patients.

PMID- 23118378
TI  - Functional results and complications following conversion of hip fusion to total
      hip replacement.
AB  - Eighteen hip fusions were converted to total   hip replacements. A constrained
      acetabular liner was used in three hips.   Mean follow up was five years (two to
      15). Two (11%) hips failed,   requiring revision surgery and two patients (11%)
      had injury to   the peroneal nerve. Heterotopic ossification developed in seven  
      (39%) hips, in one case resulting in joint ankylosis. No hips dislocated. 
      Conversion of hip fusion to hip replacement carries an increased   risk of
      heterotopic ossification and neurological injury. We advise   prophylaxis against
      heterotropic ossification. When there is concern   about hip stability we suggest
      that the use of a constrained acetabular   liner is considered. Despite the
      potential for complications, this procedure   had a high success rate and was
      effective in restoring hip function.

PMID- 23118379
TI  - Strategies for the prevention of periprosthetic joint infection.
AB  - Periprosthetic joint infection (PJI) is a devastating   complication which can
      follow a total joint arthroplasty (TJA).   Although rare, this ongoing threat
      undermines the success of TJA,   a historically reputable procedure. It has
      haunted the orthopedic   community for decades and several ongoing studies have
      provided   insights and new approaches to effectively battle this multilayered  
      problem.

PMID- 23118380
TI  - Short stems for total hip arthroplasty: initial experience with the Fitmore stem.
AB  - The use of short stems has become more popular   with the increased interest in
      less invasive approaches for total hip   arthroplasty. The curved broaches and
      stem can be inserted along   a curved track to avoid the abductor attachments.
      Short stems have   the potential of being more bone conserving by allowing for
      higher   neck retention, maintenance of the medial greater trochanter, and  
      preferential stress transfer to the proximal femur. An initial experience with
      500 new short stems (Fitmore, Zimmer   Orthopedics) stems used for total hip
      arthroplasty is reported.   No stems have been revised for aseptic loosening.

PMID- 23118381
TI  - Large diameter heads: is bigger always better?
AB  - Large femoral heads have been used with increasing   frequency over the last
      decade. The prime reason is likely the effect   of large heads on stability. The
      larger head neck ratio, combined   with the increased jump distance of larger
      heads result in a greater   arc of impingement free motion, and greater
      resistance to dislocation   in a provocative position. Multiple studies have
      demonstrated clear   clinical efficacy in diminishing dislocation rates with the
      use   of large femoral heads. With crosslinked polyethylene, wear has   been
      shown to be equivalent between larger and smaller heads. However,   the stability
      advantages of increasing diameter beyond 38 mm have   not been clearly
      demonstrated. More importantly, recent data implicates   large heads in the
      increasing prevalence of groin pain and psoas impingement.   There are clear
      benefits with larger femoral head diameters, but   the advantages of diameters
      beyond 38 mm have not yet been demonstrated   clinically.

PMID- 23118382
TI  - The painful hip: diagnosis and deliverance.
AB  - The differential diagnosis of the painful total   hip arthroplasty (resurfacing
      or total hip) includes infection,   failure of fixation (loosening), tendinitis,
      bursitis, synovitis,   adverse local tissue reaction (ALTR) to cobalt-chromium
      alloys,   and non-hip issues, such as spinal disorders, hernia, gynecologic,  
      and other pelvic pain. Assuming that the hip is the source of pain,   the first
      level question is prosthetic or non-prosthetic pain generator?   The second level
      prosthetic question is septic or aseptic? The third   level question (aseptic
      hips) is well-fixed or loose? ALTR is best   diagnosed by cross-sectional
      imaging. Successful treatment is dependent   on correct identification and
      elimination of the pain generator.   Treatment recommendations for ALTR and taper
      corrosion are evolving.

PMID- 23118383
TI  - Role and results of tapered fluted modular titanium stems in revision total hip
      arthroplasty.
AB  - Tapered, fluted, modular, titanium stems have   a long history in Europe and are
      increasing in popularity in North America.   We have reviewed the results at our
      institution looking at stem   survival and clinical outcomes. Radiological
      outcomes and quality   of life assessments have been performed and compared to
      cylindrical   non-modular cobalt chromium stems. Survival at five years was 94%. 
      This fell to 85% at ten years due to stem breakage with older designs.   Review
      of radiology showed maintenance or improvement of bone stock   in 87% of cases.
      Outcome scores were superior in tapered stems despite   worse pre-operative
      femoral deficiency. Tapered stems have proved   to be a useful alternative in
      revision total hip arthroplasty across   the spectrum of femoral bone deficiency.

PMID- 23118384
TI  - Massive bone loss: allograft-prosthetic composites and beyond.
AB  - Revision total hip arthroplasty (THA) is projected   to increase by 137% from the
      years 2005 to 2030. Reconstruction of   the femur with massive bone loss can be a
      formidable undertaking.   The goals of revision surgery are to create a stable
      construct,   preserve bone and soft tissues, augment deficient host bone, improve
      function, provide a foundation for future surgery, and create a  
      biomechanically restored hip. Options for treatment of the compromised femur  
      include: resection arthroplasty, allograft prosthetic composite   (APC), proximal
      femoral replacement, cementless fixation with a   modular tapered fluted stem,
      and impaction grafting. The purpose   of this article is to review the treatment
      options along with their   associated outcomes in the more severe femoral defects
      (Paprosky types   IIIb and IV) in revision THA.

PMID- 23118385
TI  - Osteolysis in the well-fixed socket: cup retention or revision?
AB  - Osteolysis remains a common reason for revision   after total hip arthroplasty
      (THA). For osteolysis associated with loose   cups, revision is indicated. For
      osteolysis around a well-fixed   cup, the decision is more controversial. The
      data available data   support retention of the cupwith lesional treatment,
      working through   screw holes and access channels for debridement and grafting.
      The   choice of graft material to fill defects, if any, remains controversial.
      Several   studies demonstrate good survivorship with cup retention strategies.  
      Complete revision allows more complete debridement of the lesion   and better
      graft fill, and allows implantation of a modern cup,   typically with a full line
      of liners and bearing surfaces available.   Additionally, revision allows fine
      tuning of the orientation of   the cup, which may be advantageous for optimising
      hip stability.   The author prefers to retain a well-fixed cup if it meets the
      following   criteria: it is well-fixed to intra-operative testing, it is well
      positioned,   it is of sufficient size to allow insertion of a new liner with   a
      reasonable head size, new liners are available, and the hip is   stable to intra
      operative trialing after liner insertion.

PMID- 23118386
TI  - What would you do?: challenges in hip surgery.
AB  - A moderator and panel of five experts led an   interactive session in discussing
      five challenging and interesting patient   case presentations involving surgery
      of the hip. The hip pathologies   reviewed included failed open reduction
      internal fixation of subcapital   femoral neck fracture, bilateral hip disease,
      evaluation of pain   after metal-on-metal hip arthroplasty, avascular necrosis,
      aseptic   loosening secondary to osteolysis and polyethylene wear, and management
      of ceramic femoral head fracture.

PMID- 23118387
TI  - Metal-on-metal hip arthroplasty: going, going, gone... - affirms.
AB  - Metal-on-metal hip arthroplasty gained significant   favor in the first decade of
      the millennium. However, the past several   years have seen increasing reports of
      failure, pseudotumor and other   adverse reactions. This study presents the
      results of a single center's   15-year experience with metal-on-metal total hip
      arthroplasty as   strong evidence that metal-on-metal is going, going, gone.

PMID- 23118388
TI  - Metal-on-metal hip arthroplasty: going, going, gone... - opposes.
AB  - In this paper, we will consider the current role   of metal-on-metal bearings by
      looking at three subtypes of MoM hip   arthroplasty separately: Hip resurfacing,
      large head (> 36 mm) MoM   THA and MoM THA with traditional femoral head sizes.

PMID- 23118389
TI  - Cementless fixation in total knee arthroplasty: down the boulevard of broken
      dreams - affirms.
AB  - There has been a recent increase in interest   for non-cemented fixation in total
      knee arthroplasty (TKA), however   the superiority of cement fixation is an
      ongoing debate.  Whereas the results based on Level III and IV evidence show
      similar   survivorship rates between the two types of fixation, Level I and   II
      evidence strongly support cemented fixation. United Kingdom,   Australia, Sweden,
      and New Zealand registry data show lower failure   rates and greater usage of
      cemented than non-cemented fixation.   Case series studies have also indicated
      greater functional outcomes   and lower revision rates among cemented TKAs. Non
      cemented fixation   involves more patellofemoral complications, including
      increased   susceptibility to wear due to a thinner polyethylene bearing on   the
      cementless metal-backed component. The combination of results   from registry
      data, prospective randomised studies, and meta-analyses   support the current
      superiority of cemented fixation in TKAs.

PMID- 23118390
TI  - Cementless fixation in total knee arthroplasty: down the boulevard of broken
      dreams - opposes.
AB  - In this study we present our experience with   four generations of uncemented
      total knee arthroplasty (TKA) from Smith   & Nephew: Tricon M, Tricon LS, Tricon
      II and Profix, focusing   on the failure rates correlating with each design
      change. Beginning   in 1984, 380 Tricon M, 435 Tricon LS, 305 Tricon 2 and 588
      Profix   were implanted by the senior author. The rate of revision for loosening 
      was 1.1% for the Tricon M, 1.1% for the Tricon LS, 0.5% for the   Tricon 2 with
      a HA coated tibial component, and 1.3% for the Profix   TKA. No loosening of the
      femoral component was seen with the Tricon   M, Tricon LS or Tricon 2, with no
      loosening seen of the tibial component   with the Profix TKA. Regarding revision
      for wear, the incidence   was 13.1% for the Tricon M, 6.6% for the Tricon LS,
      2.3% for the   Tricon 2, and 0% for the Profix. These results demonstrate that  
      improvements in the design of uncemented components, including increased  
      polyethylene thickness, improved polyethylene quality, and the introduction   of
      hydroxyapatite coating, has improved the outcomes of uncemented   TKA over time.

PMID- 23118391
TI  - Simultaneous-bilateral TKA: double trouble - affirms.
AB  - In this paper, we will consider the current role   of simultaneous-bilateral TKA.
      Based on available evidence, it is   our opinion that simultaneous bilateral TKA
      carries a higher risk   of morbidity and mortality and should be reserved for
      select few.

PMID- 23118392
TI  - Simultaneous-bilateral TKA: double trouble - opposes.
AB  - In this paper, we will consider the current role   of simultaneous-bilateral TKA.
      Based on available evidence, it is   our opinion that bilateral one stage TKR is
      a safe and efficacious treatment   for patients with severe bilateral arthritic
      knee disease but should   be reserved for selected patients without significant
      medical comorbidities.

PMID- 23118393
TI  - Patient specific cutting blocks are currently of no proven value.
AB  - Patient specific cutting guides generated by   preoperative Magnetic Resonance
      Imaging (MRI) of the patient's extremity   have been proposed as a method of
      improving the consistency of Total   Knee Arthroplasty (TKA) alignment and adding
      efficiency to the operative   procedure. The cost of this option was evaluated by
      quantifying the   savings from decreased operative time and instrument processing
      costs compared to the additional cost of the MRI and the guide.   Coronal plane
      alignment was measured in an unselected consecutive   series of 200 TKAs, 100
      with standard instrumentation and 100 with   custom cutting guides. While the
      cutting guides had significantly lower   total operative time and instrument
      processing time, the estimated   $322 savings was overwhelmed by the $1,500
      additional cost of the   MRI and the cutting guide. All measures of coronal plane
      alignment   were equivalent between the two groups. The data does not currently  
      support the proposition that patient specific guides add value to   TKA.

PMID- 23118394
TI  - The influence of obesity on total joint arthroplasty.
AB  - Obesity is an epidemic across both the developed   and developing nations that is
      possibly the most important current   public health factor affecting the
      morbidity and mortality of the global   population. Obese patients have the
      potential to pose several challenges   for arthroplasty surgeons from the
      standpoint of the influence obesity   has on osteoarthritic symptoms, their peri
      operative medical management,   the increased intra-operative technical demands
      on the surgeon,   the intra- and post-operative complications, the long term
      outcomes   of total hip and knee arthroplasty. Also, there is no consensus   on
      the role the arthroplasty surgeon should have in facilitating   weight loss for
      these patients, nor whether obesity should affect   the access to arthroplasty
      procedures.

PMID- 23118395
TI  - The stiff total knee arthroplasty: causes and cures.
AB  - Seven stiff total knee arthroplasties are presented   to illustrate the roles of:
      1) manipulation under general anesthesia;   2) multiple concurrent diagnoses in
      addition to stiffness; 3) extra-articular   pathology; 4) pain as part of the
      stiffness triad (pain and limits   to flexion or extension); 5) component
      internal rotation; 6) multifactorial   etiology; and 7) surgical exposure in this
      challenging clinical   problem.

PMID- 23118396
TI  - Fixed flexion deformity and total knee arthroplasty.
AB  - Fixed flexion deformities are common in osteoarthritic   knees that are indicated
      for total knee arthroplasty. The lack of   full extension at the knee results in
      a greater force of quadriceps   contracture and energy expenditure. It also
      results in slower walking   velocity and abnormal gait mechanics, overloading the
      contralateral   limb. Residual flexion contractures after TKA have been
      associated   with poorer functional scores and outcomes. Although some flexion
      contractures may resolve with time after   surgery, a substantial percentage will
      become permanent. Therefore,   it is essential to correct fixed flexion
      deformities at the time   of TKA, and be vigilant in the post-operative course to
      maintain   the correction. Surgical techniques to address pre-operative flexion
      contractures   include: adequate bone resection, ligament releases, removal of  
      posterior osteophytes, and posterior capsular releases. Post-operatively,  
      extension can be maintained with focused physiotherapy, a specially   modified
      continuous passive motion machine, a contralateral heel   lift, and splinting.

PMID- 23118397
TI  - Management of extensor mechanism rupture after TKA.
AB  - Disruption of the extensor mechanism in total   knee arthroplasty may occur by
      tubercle avulsion, patellar or quadriceps   tendon rupture, or patella fracture,
      and whether occurring intra-operatively   or post-operatively can be difficult to
      manage and is associated   with a significant rate of failure and associated
      complications.   This surgery is frequently performed in compromised tissues, and
      repairs must frequently be protected with cerclage wiring and/or   augmentation
      with local tendon (semi-tendinosis, gracilis) which   may also be used to treat
      soft-tissue loss in the face of chronic   disruption. Quadriceps rupture may be
      treated with conservative   therapy if the patient retains active extension.
      Component loosening   or loss of active extension of 20 degrees  or greater are
      clear indications   for surgical treatment of patellar fracture. Acute patellar
      tendon   disruption may be treated by primary repair. Chronic extensor failure  
      is often complicated by tissue loss and retraction can be treated   with medial
      gastrocnemius flaps, achilles tendon allografts, and   complete extensor
      mechanism allografts. Attention to fixing the   graft in full extension is
      mandatory to prevent severe extensor   lag as the graft stretches out over time.

PMID- 23118398
TI  - Single stage revision: regaining momentum.
AB  - In this paper we make the case for the use of   single-stage revision for
      infected knee arthroplasty.

PMID- 23118399
TI  - Articulating antibiotic impregnated spacers in two-stage revision of infected
      total knee arthroplasty.
AB  - Antibiotic impregnated articulating spacers are   used in two-stage revision
      total knee arthroplasty to deliver local antibiotic   therapy while preserving
      function. We have observed infection control   in greater than 95% of cases with
      functional outcomes approaching   those seen in revision for aseptic loosening.
      Higher failure has   been observed with methicillin resistant organisms.

PMID- 23118400
TI  - Wound closure: healing the collateral damage.
AB  - In this paper, we consider wound healing after   total knee arthroplasty.

PMID- 23118401
TI  - The evolving incidence and reasons for re-operation after fixed-bearing PCL
      retaining total knee arthroplasty.
AB  - PCL retaining fixed-bearing TKA is a highly successful   operation with the need
      for more surgery occurring at the rate of   approximately 0.4% per year over the
      first 27 years. The most common   cause for revision surgery is related to
      polyethylene insert failure   and accounts for approximately 50% of re
      operations. Late metastatic   infection is the next most frequent cause followed
      by patellar problems,   late instability and component loosening in decreasing
      frequency.   A myriad of rare miscellaneous problems can also occur.

PMID- 23118402
TI  - Alternatives to revision total knee arthroplasty.
AB  - Most problems encountered in complex revision   total knee arthroplasty can be
      managed with the wide range of implant   systems currently available. Modular
      metaphyseal sleeves, metallic   augments and cones provide stability even with
      significant bone   loss. Hinged designs substitute for significant ligamentous
      deficiencies.   Catastrophic failure that precludes successful reconstruction can
      be encountered. The alternatives to arthroplasty in such drastic   situations
      include knee arthrodesis, resection arthroplasty and   amputation. The relative
      indications for the selection of these   alternatives are recurrent deep
      infection, immunocompromised host,   and extensive non-reconstructible bone or
      soft-tissue defects.

PMID- 23118403
TI  - A primer in cartilage repair.
AB  - Hyaline articular cartilage has been known to   be a troublesome tissue to repair
      once damaged. Since the introduction   of autologous chondrocyte implantation
      (ACI) in 1994, a renewed   interest in the field of cartilage repair with new
      repair techniques   and the hope for products that are regenerative have
      blossomed.   This article reviews the basic science structure and function of  
      articular cartilage, and techniques that are presently available   to effect
      repair and their expected outcomes.

PMID- 23118404
TI  - Use of smart trials for soft-tissue balancing in total knee replacement surgery.
AB  - Smart trials are total knee tibial trial liners   with load bearing and alignment
      sensors that will graphically show quantitative   compartment load-bearing forces
      and component track patterns. These   values will demonstrate asymmetrical
      ligament balancing and misalignments   with the medial retinaculum temporarily
      closed. Currently surgeons   use feel and visual estimation of imbalance to
      assess soft-tissue   balancing and tracking with the medial retinaculum open,
      which results   in lower medial compartment loads and a wider anteroposterior
      tibial   tracking pattern. The sensor trial will aid the total knee replacement  
      surgeon in performing soft-tissue balancing by providing quantitative   visual
      feedback of changes in forces while performing the releases   incrementally.
      Initial experience using a smart tibial trial is   presented.

PMID- 23118405
TI  - Hand-held navigation in total knee arthroplasty.

PMID- 23118406
TI  - A prospective, multi-center, randomised trial to evaluate the efficacy of a
      cryopneumatic device on total knee arthroplasty recovery.
AB  - Pain, swelling and inflammation are expected   during the recovery from total
      knee arthroplasty (TKA) surgery.   The severity of these factors and how a
      patient copes with them   may determine the ultimate outcome of a TKA.
      Cryotherapy and compression   are frequently used modalities to mitigate these
      commonly experienced   sequelae. However, their effect on range of motion,
      functional testing,   and narcotic consumption has not been well-studied. A
      prospective, multi-center, randomised trial was conducted to   evaluate the
      effect of a cryopneumatic device on post-operative   TKA recovery. Patients were
      randomised to treatment with a cryopneumatic   device or ice with static
      compression. A total of 280 patients were   enrolled at 11 international sites.
      Both treatments were initiated   within three hours post-operation and used at
      least four times per   day for two weeks. The cryopneumatic device was titrated
      for cooling   and pressure by the patient to their comfort level. Patients were
      evaluated by physical therapists blinded to the   treatment arm. Range of motion
      (ROM), knee girth, six minute walk   test (6MWT) and timed up and go test (TUG)
      were measured pre-operatively,   two- and six-weeks post-operatively. A visual
      analog pain score   and narcotic consumption was also measured post-operatively.
      At two weeks post-operatively, both the treatment and control   groups had
      diminished ROM and function compared to pre-operatively.   Both groups had
      increased knee girth compared to pre- operatively.   There was no significant
      difference in ROM, 6MWT, TUG, or knee girth   between the 2 groups. We did find a
      significantly lower amount of   narcotic consumption (509 mg morphine
      equivalents) in the treatment   group compared with the control group (680 mg
      morphine equivalents)   at up to two weeks postop, when the cryopneumatic device
      was being   used (p < 0.05). Between two and six weeks, there was no difference  
      in the total amount of narcotics consumed between the two groups.   At six weeks,
      there was a trend toward a greater distance walked   in the 6MWT in the treatment
      group (29.4 meters versus 7.9   meters, p = 0.13). There was a significant
      difference in the satisfaction   scores of patients with their cooling regimen,
      with greater satisfaction   in the treatment group (p < 0.0001). There was no
      difference   in ROM, TUG, VAS, or knee girth at six weeks. There was no
      difference   in adverse events or compliance between the two groups. A
      cryopneumatic device used after TKA appeared to decrease the   need for narcotic
      medication from hospital discharge to 2 weeks   post-operatively. There was also
      a trend toward a greater distance   walked in the 6MWT. Patient satisfaction with
      the cryopneumatic   cooling regimen was significantly higher than with the
      control treatment.

PMID- 23118407
TI  - Hip and knee arthroplasty 2011: what's new, what's true, does it matter? Evidence
      based issues.
AB  - This conversation represents an attempt by several   arthroplasty surgeons to
      critique several abstracts presented over   the last year as well as to use them
      as a jumping off point for trying   to figure out where they fit in into our
      current understanding of   multiple issues in modern hip and knee arthroplasty.

PMID- 23118408
TI  - Stakeholder perspectives on handovers between hospital staff and general
      practitioners: an evaluation through the microsystems lens.
AB  - BACKGROUND: Much of the research on improving patient handovers has focused on
      enhancing communication within the hospital system, but there have been
      relatively few efforts aimed at addressing the challenges at the interface
      between the hospital and the primary care setting. METHODS: A qualitative
      thematic analysis using a clinical microsystems lens applied to 28 semi
      structured key stakeholder interviews in the Netherlands. Data were organised
      into seven 'virtual' clinical microsystem datasets composed of patients, hospital
      based physicians, hospital-based nurses and community-based general
      practitioners. RESULTS: Five themes that contributed to effective or ineffective
      handovers emerged from our analysis: (1) lack of adequate information; (2)
      healthcare professionals' availability and opportunity for personal contact; (3)
      feedback, teaching and protocols related to handovers; (4) information technology
      facilitated communication solutions; and (5) the role and responsibility of
      patients. Our analysis suggests that each healthcare professional attempted to
      provide the best care possible, but did this largely in isolation, and without
      the benefit of the knowledge and expertise of the other members of the
      microsystem. CONCLUSIONS: The microsystem approach offers an innovative
      organisational construct and approach to assess the gaps in 'hospital to
      community' patient handovers, by viewing the hospital to the community interface
      as a clinical microsystem continuum. Our application of the microsystem approach
      confirms and extends earlier findings about the impact of barriers on the
      continuity and safety of patient transitions and their impact on the quality of
      patient care.

PMID- 23118409
TI  - Searching for the missing pieces between the hospital and primary care: mapping
      the patient process during care transitions.
AB  - BACKGROUND: Safe patient transitions depend on effective communication and a
      functioning care coordination process. Evidence suggests that primary care
      physicians are not satisfied with communication at transition points between
      inpatient and ambulatory care, and that communication often is not provided in a
      timely manner, omits essential information, or contains ambiguities that put
      patients at risk. OBJECTIVE: Our aim was to demonstrate how process mapping can
      illustrate current handover practices between ambulatory and inpatient care
      settings, identify existing barriers and facilitators to effective transitions of
      care, and highlight potential areas for quality improvement. METHODS: We
      conducted focus group interviews to facilitate a process mapping exercise with
      clinical teams in six academic health centres in the USA, Poland, Sweden, Italy,
      Spain and the Netherlands. FINDINGS: At a high level, the process of patient
      admission to the hospital through the emergency department, inpatient care, and
      discharge back in the community were comparable across sites. In addition, the
      process maps highlighted similar barriers to providing information to primary
      care physicians, inaccurate or incomplete information on referral and discharge,
      a lack of time and priority to collaborate with counterpart colleagues, and a
      lack of feedback to clinicians involved in the handovers. CONCLUSIONS: Process
      mapping is effective in bringing together key stakeholders and makes explicit the
      mental models that frame their understanding of the clinical process. Exploring
      the barriers and facilitators to safe and reliable patient transitions highlights
      opportunities for further improvement work and illustrates ideas for best
      practices that might be transferrable to other settings.

PMID- 23118411
TI  - Hypermobility in dancers.

PMID- 23118410
TI  - Are patients discharged with care? A qualitative study of perceptions and
      experiences of patients, family members and care providers.
AB  - BACKGROUND: Advocates for quality and safety have called for healthcare that is
      patient-centred and decision-making that involves patients. OBJECTIVE: The aim of
      the paper is to explore the barriers and facilitators to patient-centred care in
      the hospital discharge process. METHODS: A qualitative study using purposive
      sampling of 192 individual interviews and 26 focus group interviews was conducted
      in five European Union countries with patients and/or family members, hospital
      physicians and nurses, and community general practitioners and nurses. A modified
      Grounded Theory approach was used to analyse the data. RESULTS: The barriers and
      facilitators were classified into 15 categories from which four themes emerged:
      (1) healthcare providers do not sufficiently prioritise discharge consultations
      with patients and family members due to time restraints and competing care
      obligations; (2) discharge communication varied from instructing patients and
      family members to shared decision-making; (3) patients often feel unprepared for
      discharge, and postdischarge care is not tailored to individual patient needs and
      preferences; and (4) pressure on available hospital beds and community resources
      affect the discharge process. CONCLUSIONS: Our findings suggest that involvement
      of patients and families in the preparations for discharge is determined by the
      extent to which care providers are willing and able to accommodate patients' and
      families' capabilities, needs and preferences. Future interventions should be
      directed at healthcare providers' attitudes and their organisation's leadership,
      with a focus on improving communication among care providers, patients and
      families, and between hospital and community care providers.

PMID- 23118412
TI  - Literacy levels required to complete routinely used patient-reported outcome
      measures in rheumatology.
AB  - OBJECTIVE: To assess the reading levels required to complete patient-reported
      outcome measures (PROs) commonly used in rheumatology clinical and research
      settings. METHODS: Ten PROs written in English were evaluated. Four reviewers
      critiqued each measure blindly using two standardized readability indexes and a
      final readability score for each PRO was agreed. RESULTS: Only six of the PROs
      met the recommended reading level for health education literature. CONCLUSION:
      Many people completing PROs will not be able to understand what they are
      answering and will be unable to give an accurate perspective on their condition.

PMID- 23118413
TI  - Bone marrow oedema of the radius presenting as tennis elbow.

PMID- 23118414
TI  - Remission of juvenile idiopathic arthritis with primary Epstein-Barr virus
      infection.

PMID- 23118415
TI  - Structure and mechanism of the polynucleotide kinase component of the bacterial
      Pnkp-Hen1 RNA repair system.
AB  - Pnkp is the end-healing and end-sealing component of an RNA repair system present
      in diverse bacteria from many phyla. Pnkp is composed of three catalytic modules:
      an N-terminal polynucleotide 5'-kinase, a central 2',3' phosphatase, and a C
      terminal ligase. Here we report the crystal structure of the kinase domain of
      Clostridium thermocellum Pnkp bound to ATP*Mg2+ (substrate complex) and ADP*Mg2+
      (product complex). The protein consists of a core P-loop phosphotransferase fold
      embellished by a distinctive homodimerization module composed of secondary
      structure elements derived from the N and C termini of the kinase domain. ATP is
      bound within a crescent-shaped groove formed by the P-loop (15GSSGSGKST23) and an
      overlying helix-loop-helix "lid." The alpha and beta phosphates are engaged by a
      network of hydrogen bonds from Thr23 and the P-loop main-chain amides; the gamma
      phosphate is anchored by the lid residues Arg120 and Arg123. The P-loop lysine
      (Lys21) and the catalytic Mg2+ bridge the ATP beta and gamma phosphates. The P
      loop serine (Ser22) is the sole enzymic constituent of the octahedral metal
      coordination complex. Structure-guided mutational analysis underscored the
      essential contributions of Lys21 and Ser22 in the ATP donor site and Asp38 and
      Arg41 in the phosphoacceptor site. Our studies suggest a catalytic mechanism
      whereby Asp38 (as general base) activates the polynucleotide 5'-OH for its
      nucleophilic attack on the gamma phosphorus and Lys21 and Mg2+ stabilize the
      transition state.

PMID- 23118417
TI  - E. coli 6S RNA release from RNA polymerase requires sigma70 ejection by
      scrunching and is orchestrated by a conserved RNA hairpin.
AB  - The 6S RNA in Escherichia coli suppresses housekeeping transcription by binding
      to RNA polymerase holoenzyme (core polymerase + sigma70) under low nutrient
      conditions and rescues sigma70-dependent transcription in high nutrient
      conditions by the synthesis of a short product RNA (pRNA) using itself as a
      template. Here we characterize a kinetic intermediate that arises during 6S RNA
      release. This state, consisting of 6S RNA and core polymerase, is related to the
      formation of a top-strand "release" hairpin that is conserved across the gamma
      proteobacteria. Deliberately slowing the intrinsic 6S RNA release rate by
      nucleotide feeding experiments reveals that sigma70 ejection occurs abruptly once
      a pRNA length of 9 nucleotides (nt) is reached. After sigma70 ejection, an
      additional 4 nt of pRNA synthesis is required before the 6S:pRNA complex is
      finally released from core polymerase. Changing the E. coli 6S RNA sequence to
      preclude formation of the release hairpin dramatically slows the speed of 6S RNA
      release but, surprisingly, does not alter the abruptness of sigma70 ejection.
      Rather, the pRNA size required to trigger sigma70 release increases from 9 nt to
      14 nt. That a precise pRNA length is required to trigger sigma70 release either
      with or without a hairpin implicates an intrinsic "scrunching"-type release
      mechanism. We speculate that the release hairpin serves two primary functions in
      the gamma-proteobacteria: First, its formation strips single-stranded "-10" 6S
      RNA interactions away from sigma70. Second, the formation of the hairpin
      accumulates RNA into a region of the polymerase complex previously associated
      with DNA scrunching, further destabilizing the 6S:pRNA:polymerase complex.

PMID- 23118416
TI  - Inhibition of polyadenylation reduces inflammatory gene induction.
AB  - Cordycepin (3' deoxyadenosine) has long been used in the study of in vitro
      assembled polyadenylation complexes, because it terminates the poly(A) tail and
      arrests the cleavage complex. It is derived from caterpillar fungi, which are
      highly prized in Chinese traditional medicine. Here we show that cordycepin
      specifically inhibits the induction of inflammatory mRNAs by cytokines in human
      airway smooth muscle cells without affecting the expression of control mRNAs.
      Cordycepin treatment results in shorter poly(A) tails, and a reduction in the
      efficiency of mRNA cleavage and transcription termination is observed, indicating
      that the effects of cordycepin on 3' processing in cells are similar to those
      described in in vitro reactions. For the CCL2 and CXCL1 mRNAs, the effects of
      cordycepin are post-transcriptional, with the mRNA disappearing during or
      immediately after nuclear export. In contrast, although the recruitment of RNA
      polymerase II to the IL8 promoter is also unaffected, the levels of nascent
      transcript are reduced, indicating a defect in transcription elongation. We show
      that a reporter construct with 3' sequences from a histone gene is unaffected by
      cordycepin, while CXCL1 sequences confer cordycepin sensitivity to the reporter,
      demonstrating that polyadenylation is indeed required for the effect of
      cordycepin on gene expression. In addition, treatment with another polyadenyation
      inhibitor and knockdown of poly(A) polymerase alpha also specifically reduced the
      induction of inflammatory mRNAs. These data demonstrate that there are
      differences in the 3' processing of inflammatory and housekeeping genes and
      identify polyadenylation as a novel target for anti-inflammatory drugs.

PMID- 23118419
TI  - Exposure to light at night, nocturnal urinary melatonin excretion, and
      obesity/dyslipidemia in the elderly: a cross-sectional analysis of the HEIJO-KYO
      study.
AB  - CONTEXT: Obesity and exposure to light at night (LAN) have increased globally.
      Although LAN suppresses melatonin secretion and disturbs body mass regulation in
      experimental settings, its associations with melatonin secretion, obesity, and
      other metabolic consequences in uncontrolled home settings remain unclear.
      OBJECTIVE: The aim of this study was to determine the association of exposure to
      LAN in an uncontrolled home setting with melatonin secretion, obesity,
      dyslipidemia, and diabetes. DESIGN AND PARTICIPANTS: A cross-sectional study was
      performed in 528 elderly individuals (mean age, 72.8 yr). MEASURES: The intensity
      of LAN in the bedroom was measured at 1-min intervals during two consecutive
      nights, along with overnight urinary melatonin excretion and metabolic
      parameters. RESULTS: Compared with the Dim group (average <3 lux; n = 383), the
      LAN group (average >=3 lux; n = 145) showed significantly higher body weight
      (adjusted mean, 58.8 vs. 56.6 kg; P = 0.01), body mass index (23.3 vs. 22.7
      kg/m(2); P = 0.04), waist circumference (84.9 vs. 82.8 cm; P = 0.01),
      triglyceride levels (119.7 vs. 99.5 mg/dl; P < 0.01), and low-density lipoprotein
      cholesterol levels (128.6 vs. 122.2 mg/dl; P = 0.04), and showed significantly
      lower high-density lipoprotein cholesterol levels (57.4 vs. 61.3 mg/dl; P =
      0.02). These associations were independent of numerous potential confounders,
      including urinary melatonin excretion. Furthermore, LAN exposure is associated
      with higher odds ratios (ORs) for obesity (body mass index: OR, 1.89; P = 0.02;
      abdominal: OR, 1.62; P = 0.04) and dyslipidemia (OR, 1.72; P = 0.02) independent
      of demographic and socioeconomic parameters. In contrast, urinary melatonin
      excretion and glucose parameters did not show significant differences between the
      two groups. CONCLUSIONS: Exposure to LAN in an uncontrolled home setting is
      associated with impaired obese and lipid parameters independent of nocturnal
      urinary melatonin excretion in elderly individuals. Moreover, LAN exposure is
      associated with higher ORs for obesity and dyslipidemia independent of
      demographic and socioeconomic parameters.

PMID- 23118418
TI  - A structure-based model of RIG-I activation.
AB  - A series of high-resolution crystal structures of RIG-I and RIG-I:dsRNA
      cocrystals has recently been reported. Comparison of these structures provides
      considerable insight into how this innate immune pattern recognition receptor is
      activated upon detecting and binding a certain class of viral RNAs.

PMID- 23118420
TI  - Immunoreactivity score using an anti-sst2A receptor monoclonal antibody strongly
      predicts the biochemical response to adjuvant treatment with somatostatin analogs
      in acromegaly.
AB  - CONTEXT: Somatostatin receptor subtype 2 (sst2A) protein expression has been
      demonstrated to positively correlate with somatostatin analog treatment outcome
      in GH-secreting adenomas. Recently, a new rabbit monoclonal anti-sst2A antibody
      (clone UMB-1) has been validated as a reliable method to selectively detect sst2A
      protein levels in formalin-fixed tissues. OBJECTIVE: The aim of the study was to
      establish whether the evaluation of sst2A protein levels, assessed with a routine
      reproducible immunohistochemistry protocol using UMB-1 antibody, may predict the
      successful adjuvant therapy with somatostatin analogs in acromegalic patients.
      DESIGN, SETTING, AND PATIENTS: Thirty-six acromegalic patients from our referral
      hospital were evaluated retrospectively. Sst2A expression analysis was performed
      by immunohistochemistry in 25 patients and by quantitative RT-PCR in 26 patients.
      Sst2A immunoreactivity was evaluated using an immunoreactivity score (IRS), which
      takes into account both the percentage of positive cells and staining intensity.
      INTERVENTIONS: Patients with persistent disease after surgery (n = 26) were
      treated with somatostatin analogs for a median duration of 6 months. MAIN OUTCOME
      MEASURE: GH and IGF-I levels were measured before and after postoperative
      treatment. RESULTS: Sst2A IRS showed a significant positive correlation with both
      GH (P = 0.039) and IGF-I (P = 0.001) suppression by octreotide. Sst2A IRS was
      negatively associated with IGF-I levels reached after treatment (P = 0.001), and
      patients that achieved IGF-I normalization showed significantly higher sst2A IRS
      compared to the group that was not normalized (P = 0.002). A sst2A IRS of at
      least 5 showed a sensitivity of 86% and a specificity of 91% in predicting IGF-I
      normalization during adjuvant octreotide treatment. CONCLUSION: Sst2A IRS with
      the anti-sst2A antibody UMB-1 represents a valid tool in the clinical practice to
      identify acromegalic patients likely to be responders to adjuvant therapy with
      the currently available somatostatin analogs.

PMID- 23118421
TI  - Cerebrospinal fluid levels of leptin, proopiomelanocortin, and agouti-related
      protein in human pregnancy: evidence for leptin resistance.
AB  - CONTEXT: Leptin suppresses appetite by modulating the expression of hypothalamic
      neuropeptides including proopiomelanocortin (POMC) and agouti-related peptide
      (AgRP). Yet during pregnancy, caloric consumption increases despite elevated
      plasma leptin levels. DESIGN AND PARTICIPANTS: To investigate this paradox, we
      measured leptin and soluble leptin receptor in plasma and leptin, POMC, and AgRP
      in cerebrospinal fluid (CSF) from 21 fasting pregnant women before delivery by
      cesarean section at a university hospital and from 14 fasting nonpregnant women.
      RESULTS: Prepregnancy body mass index was 24.6 +/- 1.1 (SE) vs. 31.3 +/- 1.3 at
      term vs. 26.5 +/- 1.6 kg/m(2) in controls. Plasma leptin (32.9 +/- 4.6 vs. 16.7
      +/- 3.0 ng/ml) and soluble leptin receptor (30.9 +/- 2.3 vs. 22.1 +/- 1.4 ng/ml)
      levels were significantly higher in pregnant women. However, mean CSF leptin did
      not differ between the two groups (283 +/- 34 vs. 311 +/- 32 pg/ml), consistent
      with a relative decrease in leptin transport into CSF during pregnancy.
      Accordingly, the CSF/plasma leptin percentage was 1.0 +/- 0.01% in pregnant
      subjects vs. 2.1 +/- 0.2% in controls (P < 0.0001). Mean CSF AgRP was
      significantly higher in pregnant subjects (32.3 +/- 2.7 vs. 23.5 +/- 2.5 pg/ml; P
      = 0.03). Mean CSF POMC was not significantly different in pregnant subjects (200
      +/- 13.6 vs. 229 +/- 17.3 fmol/ml; P = 0.190). However, the mean AgRP/POMC ratio
      was significantly higher among pregnant women (P = 0.003), consistent with an
      overall decrease in melanocortin tone favoring increased food intake during
      pregnancy. CONCLUSIONS: These data demonstrate that despite peripheral
      hyperleptinemia, positive energy balance is achieved during pregnancy by a
      relative decrease in central leptin concentrations and resistance to leptin's
      effects on target neuropeptides that regulate energy balance.

PMID- 23118422
TI  - Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study: baseline
      characteristics of enrolled subjects.
AB  - BACKGROUND: The Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study
      is a prospective evaluation of the natural history impaired glucose regulation.
      DESIGN AND METHODS: The eligibility requirements include age 18-65 yr, history of
      type 2 diabetes in one or both parents, normal fasting plasma glucose (FPG) or
      normal glucose tolerance, and African-American or Caucasian status. Participants
      underwent assessments (including dietary and exercise behavior, clinical
      examination, glucose tolerance, insulin sensitivity, beta-cell function, body
      composition, energy expenditure) during 2.25-5.5 yr of quarterly follow-up. The
      primary outcome is the occurrence of prediabetes. Baseline data are presented for
      the 376 enrolled participants. The cohort was also compared with National Health
      and Nutrition Examination Survey 2007/2008 participants meeting the age and
      glycemic criteria for the POP-ABC study. RESULTS: The POP-ABC cohort [mean (+/
      SD) age was 44.2 +/- 10.6 yr] was 57.7% African-Americans, 42.3% Caucasians, and
      70.7% females; 86% had one parent with diabetes and 14% had both parents
      affected. Although greater than 70% of the cohort were employed and 75% had more
      than 13 yr of education, more African-Americans reported incomes less than
      $20,000 and fewer reported incomes more than $75,000 compared with Caucasians.
      Compared with Caucasians, African-Americans had a higher body mass index (31.3 +/
      7.8 vs. 28.8 +/- 7.8 kg/m(2), P = 0.001), a lower FPG (90.0 +/- 7.72 vs. 92.2 +/
      7.60 mg/dl, P = 0.008), higher glycosylated hemoglobin, lower triglycerides, and
      similar blood pressure, and homeostasis model assessment of insulin resistance,
      homeostasis model assessment of beta-cell function, high-density lipoprotein, and
      low-density lipoprotein cholesterol levels. Compared with a cross-section of U.S.
      subjects (National Health and Nutrition Examination Survey 2007/2008) with normal
      FPG and normal glucose tolerance, participants in the POP-ABC study had similar
      lipid profile but were more educated and had higher body mass index, glycosylated
      hemoglobin, and blood pressure. CONCLUSIONS: The POP-ABC study has successfully
      enrolled healthy African-American and Caucasian adults with parental type 2
      diabetes mellitus. The study will generate novel data on incidence rates and
      predictors of prediabetes, and clarify the role of race/ethnicity on early
      dysglycemia.

PMID- 23118424
TI  - Effects of the FSH-beta-subunit promoter polymorphism -211G->T on the
      hypothalamic-pituitary-ovarian axis in normally cycling women indicate a gender
      specific regulation of gonadotropin secretion.
AB  - CONTEXT: A polymorphism in the FSHB promoter (-211G->T, rs10835638) was found to
      be associated with decreased FSH, elevated LH, reduced testosterone, and
      oligozoospermia in males. Although FSH is pivotal for ovarian function, no data
      on consequences of FSHB -211G->T are available in females. OBJECTIVE: We studied
      the effects of FSHB -211G->T on the hypothalamic-pituitary-ovarian axis in women.
      DESIGN AND SETTING: In a university-based in vitro fertilization unit, women
      undergoing standardized diagnostics were genotyped and compared with a fertile
      control group. PATIENTS: The study group consisted of 365 thoroughly
      characterized women with normal menstrual cycle intervals and proven ovulation,
      with predominantly male-factor infertility. The independently recruited control
      group included 438 women with proven fertility and no history of abortions. MAIN
      OUTCOME MEASURES: Distribution of alleles and genotypes were compared between the
      study group and controls. In the study group, associations of endocrine
      parameters with FSHB -211G->T were assessed. RESULTS: Allele and genotype
      frequencies were not significantly different between the study population and
      controls (T-allele: 14.4 vs. 16.6%; TT-homozygotes: 2.5 vs. 3.2%). The FSHB -211G
      >T TT-genotype was strongly associated with elevated FSH (TT-homozygosity effect
      2.05 U/liter, P = 0.003). LH increased with the number of T-alleles (1.30 U/liter
      per T-allele, P < 0.001). Additionally, FSHB -211G->T was associated with reduced
      progesterone (-1.96 ng/ml per T-allele, P = 0.047). CONCLUSIONS: This is a report
      on phenotypic consequences of FSHB -211G->T on the hypothalamic-pituitary-ovarian
      axis in women. The findings, partially contradictory to those in men, point to a
      gender-specific compensatory mechanism of gonadotropin secretion, probably
      involving progesterone.

PMID- 23118423
TI  - Fine mapping of loci linked to autoimmune thyroid disease identifies novel
      susceptibility genes.
AB  - CONTEXT: Genetic factors play a major role in the etiology of autoimmune thyroid
      disease (AITD) including Graves' disease (GD) and Hashimoto's thyroiditis (HT).
      We have previously identified three loci on chromosomes 10q, 12q, and 14q that
      showed strong linkage with AITD, HT, and GD, respectively. OBJECTIVES: The
      objective of the study was to identify the AITD susceptibility genes at the 10q,
      12q, and 14q loci. DESIGN AND PARTICIPANTS: Three hundred forty North American
      Caucasian AITD patients and 183 healthy controls were studied. The 10q, 12q, and
      14q loci were fine mapped by genotyping densely spaced single-nucleotide
      polymorphisms (SNPs) using the Illumina GoldenGate genotyping platform. Case
      control association analyses were performed using the UNPHASED computer package.
      Associated SNPs were reanalyzed in a replication set consisting of 238 AITD
      patients and 276 controls. RESULTS: Fine mapping of the AITD locus, 10q, showed
      replicated association of the AITD phenotype (both GD and HT) with SNP rs6479778.
      This SNP was located within the ARID5B gene recently reported to be associated
      with rheumatoid arthritis and GD in Japanese. Fine mapping of the GD locus, 14q,
      revealed replicated association of the GD phenotype with two markers, rs12147587
      and rs2284720, located within the NRXN3 and TSHR genes, respectively.
      CONCLUSIONS: Fine mapping of three linked loci identified novel susceptibility
      genes for AITD. The discoveries of new AITD susceptibility genes will engender a
      new understanding of AITD etiology.

PMID- 23118425
TI  - Interferon-gamma and tumor necrosis factor-alpha sustain secretion of specific
      CXC chemokines in human thyrocytes: a first step toward a differentiation between
      autoimmune and tumor-related inflammation?
AB  - CONTEXT: Chemokines are chemotactic cytokines responsible for the attraction and
      recruitment of different cell types during leukocyte infiltration, the
      histopathological hallmark of autoimmunity. Previous data demonstrate that
      thyrocytes secrete CXC chemokines, particularly CXCL8 and CXCL10. However, the
      physiopathological significance of such secretion and the effects of a
      combination of proinflammatory stimuli in terms of preferential CXCL8 and CXCL10
      release remain unclear. OBJECTIVE: The aim of this study was to investigate
      whether the secretion of chemokines by human thyrocytes is a generalized
      inflammatory response or whether it is dependent upon specific proinflammatory
      stimuli. METHODS: CXCL8 and CXCL10 were measured in supernatants of human
      thyrocytes in primary cultures basally and after 24 h stimulation with interferon
      gamma (IFNgamma) (1000 U/ml) and TNFalpha (10 ng/ml), alone or in combination.
      RESULTS: CXCL8 but not CXCL10 was detected in basal conditions. The two
      chemokines showed differences in their response to proinflammatory cytokines.
      Indeed, significant secretion of CXCL10 was induced by IFNgamma (P < 0.01) and
      not TNFalpha, whereas CXCL8 was secreted in response to TNFalpha (P < 0.01) being
      inhibited by IFNgamma (P < 0.01). The combination of TNFalpha plus IFNgamma
      synergistically increased the IFNgamma-induced CXCL10 secretion (P < 0.01) and
      reversed the TNFalpha-induced CXCL8 secretion (P < 0.01). CONCLUSIONS: These
      results confirm that human thyrocytes secrete CXC chemokines and demonstrate that
      the secretion of CXCL8 and CXCL10 is sustained by specific proinflammatory
      cytokines or their combination, which ultimately determines the nature of the
      infiltrating lymphocytes in human thyroid diseases. These results indirectly
      support a major role for CXCL10 in thyroid autoimmunity whereas CXCL8 might be
      involved in tumor-related inflammation.

PMID- 23118426
TI  - Evidence for chromosome 2p16.3 polycystic ovary syndrome susceptibility locus in
      affected women of European ancestry.
AB  - CONTEXT: A previous genome-wide association study in Chinese women with
      polycystic ovary syndrome (PCOS) identified a region on chromosome 2p16.3
      encoding the LH/choriogonadotropin receptor (LHCGR) and FSH receptor (FSHR) genes
      as a reproducible PCOS susceptibility locus. OBJECTIVE: The objective of the
      study was to determine the role of the LHCGR and/or FSHR gene in the etiology of
      PCOS in women of European ancestry. DESIGN: This was a genetic association study
      in a European ancestry cohort of women with PCOS. SETTING: The study was
      conducted at an academic medical center. PARTICIPANTS: Participants in the study
      included 905 women with PCOS diagnosed by National Institutes of Health criteria
      and 956 control women. INTERVENTION: We genotyped 94 haplotype-tagging single
      nucleotide polymorphisms and two coding single-nucleotide polymorphisms mapping
      to the coding region of LHCGR and FSHR plus 20 kb upstream and downstream of the
      genes and test for association in the case control cohort and for association
      with nine quantitative traits in the women with PCOS. RESULTS: We found strong
      evidence for an association of PCOS with rs7562215 (P = 0.0037) and rs10495960 (P
      = 0.0046). Although the marker with the strongest association in the Chinese PCOS
      genome-wide association study (rs13405728) was not informative in the European
      populations, we identified and genotyped three markers (rs35960650, rs2956355,
      and rs7562879) within 5 kb of rs13405728. Of these, rs7562879 was nominally
      associated with PCOS (P = 0.020). The strongest evidence for association mapping
      to FSHR was observed with rs1922476 (P = 0.0053). Furthermore, markers with the
      FSHR gene region were associated with FSH levels in women with PCOS. CONCLUSIONS:
      Fine mapping of the chromosome 2p16.3 Chinese PCOS susceptibility locus in a
      European ancestry cohort provides evidence for association with two independent
      loci and PCOS. The gene products LHCGR and FSHR therefore are likely to be
      important in the etiology of PCOS, regardless of ethnicity.

PMID- 23118427
TI  - Circulating microRNAs identified in a genome-wide serum microRNA expression
      analysis as noninvasive biomarkers for endometriosis.
AB  - CONTEXT: There is currently no reliable noninvasive biomarker for the clinical
      diagnosis of endometriosis. Previous analyses have reported that circulating
      microRNAs (miRNAs) can serve as biomarkers for a number of diseases. OBJECTIVE:
      The study aims to detect the serum miRNAs that are differentially expressed
      between endometriosis patients and negative controls to evaluate the potential of
      these miRNAs as diagnostic markers for endometriosis. DESIGN: A total of 765
      serum miRNAs were profiled using a TaqMan microRNA array in a pool of 10
      endometriosis patients and a pool of 10 negative controls, and a set of selected
      miRNAs were further analyzed in a validation cohort consisting of sera from 60
      patients and 25 controls including 10 samples used in array profiling. RESULTS:
      The relative expression levels of miR-199a and miR-122 were found to be up
      regulated in endometriosis patient samples compared with control samples, whereas
      miR-145*, miR-141*, miR-542-3p, and miR-9* were down-regulated in endometriosis
      patients. Importantly, the relative expression of miR-199a (P < 0.05) and miR-122
      can be used to discriminate between severe and mild endometriosis. We also found
      that miR-199a is well correlated with pelvic adhesion and lesion distribution (P
      < 0.05) and associated with hormone-mediated signaling pathways. Furthermore, we
      investigated the diagnostic value of these molecules and confirmed the optimal
      combination of miR-199a, miR-122, miR-145*, and miR-542-3p with area under the
      curve of 0.994 (95% confidence interval = 0.984-1.000, P < 0.001) and a cutoff
      point (0.4950) of 93.22% sensitivity and 96.00% specificity. CONCLUSIONS: Our
      study demonstrated that the circulating miRNAs miR-199a, miR-122, miR-145*, and
      miR-542-3p could potentially serve as noninvasive biomarkers for endometriosis.
      miR-199a may also play an important role in the progression of the disease. This
      is the first report that circulating miRNAs serve as biomarkers of endometriosis.

PMID- 23118429
TI  - Clinical review: Klinefelter syndrome--a clinical update.
AB  - CONTEXT: Recently, new clinically important information regarding Klinefelter
      syndrome (KS) has been published. We review aspects of epidemiology,
      endocrinology, metabolism, body composition, and neuropsychology with reference
      to recent genetic discoveries. EVIDENCE ACQUISITION: PubMed was searched for
      "Klinefelter," "Klinefelter's," and "XXY" in titles and abstracts. Relevant
      papers were obtained and reviewed, as well as other articles selected by the
      authors. EVIDENCE SYNTHESIS: KS is the most common sex chromosome disorder in
      males, affecting one in 660 men. The genetic background is the extra X
      chromosome, which may be inherited from either parent. Most genes from the extra
      X undergo inactivation, but some escape and serve as the putative genetic cause
      of the syndrome. KS is severely underdiagnosed or is diagnosed late in life,
      roughly 25% are diagnosed, and the mean age of diagnosis is in the mid-30s. KS is
      associated with an increased morbidity resulting in loss of approximately 2 yr in
      life span with an increased mortality from many different diseases. The key
      findings in KS are small testes, hypergonadotropic hypogonadism, and cognitive
      impairment. The hypogonadism may lead to changes in body composition and a risk
      of developing metabolic syndrome and type 2 diabetes. The cognitive impairment is
      mainly in the area of language processing. Boys with KS are often in need of
      speech therapy, and many suffer from learning disability and may benefit from
      special education. Medical treatment is mainly testosterone replacement therapy
      to alleviate acute and long-term consequences of hypogonadism as well as treating
      or preventing the frequent comorbidity. CONCLUSIONS: More emphasis should be
      placed on increasing the rate of diagnosis and generating evidence for timing and
      dose of testosterone replacement. Treatment of KS should be a multidisciplinary
      task including pediatricians, speech therapists, general practitioners,
      psychologists, infertility specialists, urologists, and endocrinologists.

PMID- 23118428
TI  - PCOS is associated with increased CD11c expression and crown-like structures in
      adipose tissue and increased central abdominal fat depots independent of obesity.
AB  - CONTEXT: Adipose tissue macrophage (ATM) infiltration is a major pathway for
      obesity-induced insulin resistance but has not been studied as a mechanism for
      insulin resistance in PCOS. OBJECTIVE: We tested whether polycystic ovary
      syndrome (PCOS) is associated with increased ATM infiltration, especially of
      inflammatory subtype identified by the CD11c marker. DESIGN AND SETTING: We
      conducted a case-control study at an academic medical center in the United
      States. PARTICIPANTS AND INTERVENTIONS: Fourteen PCOS and 14 control women of
      similar age and body mass index (BMI) underwent a gluteal fat biopsy. Markers of
      ATM, integrins, TNF-alpha, and adiponectin, were analyzed by quantitative RT-PCR
      using a standard curve method. Crown-like structures (CLS) were identified by
      immunohistochemistry. Abdominal magnetic resonance imaging and frequently sampled
      i.v. glucose tolerance test were performed to assess abdominal fat and insulin
      sensitivity (SI). MAIN OUTCOME: Women with PCOS were compared with control women
      of similar age and BMI for ATM markers, CLS density, adipose tissue expression of
      inflammatory cytokines and adiponectin, SI, and abdominal fat depots. RESULTS:
      Women with PCOS had an increase in CD11c expression (P = 0.03), CLS density (P =
      0.001), alpha5 expression (P = 0.009), borderline increase in TNF-alpha
      expression (P = 0.08), and a decrease in adiponectin expression (P = 0.02) in
      gluteal adipose tissue. Visceral (P = 0.009) and sc abdominal fat (P = 0.005)
      were increased in PCOS. SI was lower in PCOS (P = 0.008). CONCLUSIONS: PCOS is
      associated with an increase in CD11c expression and CLS density and a decrease in
      adiponectin expression in sc adipose tissue. Additionally, PCOS is associated
      with higher central abdominal fat depots independent of BMI. These alterations
      are present among mostly nonobese women and could represent mechanisms for
      insulin resistance.

PMID- 23118430
TI  - The selective phosphodiesterase-5 inhibitor tadalafil induces microvascular and
      metabolic effects in type 2 diabetic postmenopausal females.
AB  - OBJECTIVE: The objective of the study was to explore the acute in vivo effects of
      the selective phosphodiesterase-5 inhibitor tadalafil on local microcirculation
      and regional metabolism in skeletal muscle and adipose tissue (AT). DESIGN,
      SETTING, AND PARTICIPANTS: We studied eight postmenopausal female patients with
      type 2 diabetes (T2D) and eight nondiabetic controls (Ctrl) in the postabsorptive
      state and 180 min after the administration of tadalafil 10 mg. Intramuscular and
      sc microdialysis were combined with measurements of forearm (FBF) and AT blood
      flow as well as with arterial and deep venous blood sampling. Muscle capillary
      recruitment, as ascertained by the permeability surface area product for glucose
      (PS(glu)), forearm glucose uptake (FGU), interstitial lactate, and glycerol
      concentrations, was measured. RESULTS: When compared with Ctrl, T2D patients
      exhibited lower (P = 0.01) PS(glu) but similar FGU and FBF. After tadalafil,
      PS(glu) (P = 0.01) and muscle interstitial-arterial (I-A) lactate concentration
      gradient (P < 0.01) increased significantly in both groups, whereas FBF, FGU, and
      I-A glycerol remained unchanged. In AT, tadalafil did not significantly affect
      local blood flow, whereas the sc interstitial (I) lactate and I-A lactate
      concentrations increased (P < 0.01), and the I-A glycerol decreased in both
      groups. Finally, in multivariate analysis the PS(glu) was a strong and
      independent predictor of muscle glucose disposal (beta: 0.737 and 0.963, P <
      0.05, in Ctrl and T2D, respectively). CONCLUSIONS: Tadalafil emerges as an
      acutely acting modulator of microvascular recruitment and glucose metabolism in
      skeletal muscle and adipose tissue. We suggest that selective phosphodiesterase-5
      blockade may provide a path forward to new therapeutics in the setting of insulin
      resistance.

PMID- 23118431
TI  - As it happens: current directions in experimental evolution.
AB  - Recent decades have seen a significant rise in studies in which evolution is
      observed and analysed directly-as it happens-under replicated, controlled
      conditions. Such 'experimental evolution' approaches offer a degree of resolution
      of evolutionary processes and their underlying genetics that is difficult or even
      impossible to achieve in more traditional comparative and retrospective analyses.
      In principle, experimental populations can be monitored for phenotypic and
      genetic changes with any desired level of replication and measurement precision,
      facilitating progress on fundamental and previously unresolved questions in
      evolutionary biology. Here, we summarize 10 invited papers in which experimental
      evolution is making significant progress on a variety of fundamental questions.
      We conclude by briefly considering future directions in this very active field of
      research, emphasizing the importance of quantitative tests of theories and the
      emerging role of genome-wide re-sequencing.

PMID- 23118432
TI  - Leaf morphology shift: new data and analysis support climate link.

PMID- 23118433
TI  - Leaf morphology shift is not linked to climate change.

PMID- 23118434
TI  - Monsters are people too.
AB  - Animals, including dogs, dolphins, monkeys and man, follow gaze. What mediates
      this bias towards the eyes? One hypothesis is that primates possess a distinct
      neural module that is uniquely tuned for the eyes of others. An alternative
      explanation is that configural face processing drives fixations to the middle of
      peoples' faces, which is where the eyes happen to be located. We distinguish
      between these two accounts. Observers were presented with images of people, non
      human creatures with eyes in the middle of their faces ('humanoids') or creatures
      with eyes positioned elsewhere ('monsters'). There was a profound and significant
      bias towards looking early and often at the eyes of humans and humanoids and
      also, critically, at the eyes of monsters. These findings demonstrate that the
      eyes, and not the middle of the head, are being targeted by the oculomotor
      system.

PMID- 23118435
TI  - Harsh childhood environmental characteristics predict exploitation and
      retaliation in humans.
AB  - Across and within societies, people vary in their propensities towards
      exploitative and retaliatory defection in potentially cooperative interaction. We
      hypothesized that this variation reflects adaptive responses to variation in cues
      during childhood that life will be harsh, unstable and short--cues that
      probabilistically indicate that it is in one's fitness interests to exploit co
      operators and to retaliate quickly against defectors. Here, we show that
      childhood exposure to family neglect, conflict and violence, and to neighbourhood
      crime, were positively associated for men (but not women) with exploitation of an
      interaction partner and retaliatory defection after that partner began to defect.
      The associations between childhood environment and both forms of defection for
      men appeared to be mediated by participants' endorsement of a 'code of honour'.
      These results suggest that individual differences in mutual benefit cooperation
      are not merely due to genetic noise, random developmental variation or the
      operation of domain-general cultural learning mechanisms, but rather, might
      reflect the adaptive calibration of social strategies to local social-ecological
      conditions.

PMID- 23118437
TI  - A new stem-neopterygian fish from the Middle Triassic of China shows the earliest
      over-water gliding strategy of the vertebrates.
AB  - Flying fishes are extraordinary aquatic vertebrates capable of gliding great
      distances over water by exploiting their enlarged pectoral fins and asymmetrical
      caudal fin. Some 50 species of extant flying fishes are classified in the
      Exocoetidae (Neopterygii: Teleostei), which have a fossil record no older than
      the Eocene. The Thoracopteridae is the only pre-Cenozoic group of non-teleosts
      that shows an array of features associated with the capability of over-water
      gliding. Until recently, however, the fossil record of the Thoracopteridae has
      been limited to the Upper Triassic of Austria and Italy. Here, we report the
      discovery of exceptionally well-preserved fossils of a new thoracopterid flying
      fish from the Middle Triassic of China, which represents the earliest evidence of
      an over-water gliding strategy in vertebrates. The results of a phylogenetic
      analysis resolve the Thoracopteridae as a stem-group of the Neopterygii that is
      more crown-ward than the Peltopleuriformes, yet more basal than the
      Luganoiiformes. As the first record of the Thoracopteride in Asia, this new
      discovery extends the geographical distribution of this group from the western to
      eastern rim of the Palaeotethys Ocean, providing new evidence to support the
      Triassic biological exchanges between Europe and southern China. Additionally,
      the Middle Triassic date of the new thoracopterid supports the hypothesis that
      the re-establishment of marine ecosystems after end-Permian mass extinction is
      more rapid than previously thought.

PMID- 23118436
TI  - The paradox of extreme high-altitude migration in bar-headed geese Anser indicus.
AB  - Bar-headed geese are renowned for migratory flights at extremely high altitudes
      over the world's tallest mountains, the Himalayas, where partial pressure of
      oxygen is dramatically reduced while flight costs, in terms of rate of oxygen
      consumption, are greatly increased. Such a mismatch is paradoxical, and it is not
      clear why geese might fly higher than is absolutely necessary. In addition,
      direct empirical measurements of high-altitude flight are lacking. We test
      whether migrating bar-headed geese actually minimize flight altitude and make use
      of favourable winds to reduce flight costs. By tracking 91 geese, we show that
      these birds typically travel through the valleys of the Himalayas and not over
      the summits. We report maximum flight altitudes of 7290 m and 6540 m for
      southbound and northbound geese, respectively, but with 95 per cent of locations
      received from less than 5489 m. Geese travelled along a route that was 112 km
      longer than the great circle (shortest distance) route, with transit ground
      speeds suggesting that they rarely profited from tailwinds. Bar-headed geese from
      these eastern populations generally travel only as high as the terrain beneath
      them dictates and rarely in profitable winds. Nevertheless, their migration
      represents an enormous challenge in conditions where humans and other mammals are
      only able to operate at levels well below their sea-level maxima.

PMID- 23118439
TI  - Microdosimetry of X-ray-irradiated gold nanoparticles.
AB  - The use of contrast agents, particularly those made of high atomic number
      elements like gold nanoparticles, to enhance the X-ray absorption properties of
      tissue has recently gained attention in the context of radiotherapy treatments.
      Because these contrast agents alter the secondary electron field in the
      irradiated medium by adding an Auger electron component, it is necessary to
      determine the change in the microdosimetric spectra brought about by the
      incorporation of such agents. Using Monte Carlo simulation, it is shown that the
      linear energy transfer and the beam quality factor in the vicinity of a gold
      nanoparticle irradiated with kilovoltage X-ray beams increase substantially when
      compared with irradiation without the gold nanoparticles present.

PMID- 23118438
TI  - Increased conspicuousness can explain the match between visual sensitivities and
      blue plumage colours in fairy-wrens.
AB  - Colour signals are expected to match visual sensitivities of intended receivers.
      In birds, evolutionary shifts from violet-sensitive (V-type) to ultraviolet
      sensitive (U-type) vision have been linked to increased prevalence of colours
      rich in shortwave reflectance (ultraviolet/blue), presumably due to better
      perception of such colours by U-type vision. Here we provide the first test of
      this widespread idea using fairy-wrens and allies (Family Maluridae) as a model,
      a family where shifts in visual sensitivities from V- to U-type eyes are
      associated with male nuptial plumage rich in ultraviolet/blue colours. Using
      psychophysical visual models, we compared the performance of both types of visual
      systems at two tasks: (i) detecting contrast between male plumage colours and
      natural backgrounds, and (ii) perceiving intraspecific chromatic variation in
      male plumage. While U-type outperforms V-type vision at both tasks, the crucial
      test here is whether U-type vision performs better at detecting and
      discriminating ultraviolet/blue colours when compared with other colours. This
      was true for detecting contrast between plumage colours and natural backgrounds
      (i), but not for discriminating intraspecific variability (ii). Our data indicate
      that selection to maximize conspicuousness to conspecifics may have led to the
      correlation between ultraviolet/blue colours and U-type vision in this clade of
      birds.

PMID- 23118440
TI  - The effect of dose heterogeneity on radiation risk in medical imaging.
AB  - The current estimations of risk associated with medical imaging procedures rely
      on assessing the organ dose via direct measurements or simulation. The dose to
      each organ is assumed to be homogeneous. To take into account the differences in
      radiation sensitivities, the mean organ doses are weighted by a corresponding
      tissue-weighting coefficients provided by ICRP to calculate the effective dose,
      which has been used as a surrogate of radiation risk. However, those coefficients
      were derived under the assumption of a homogeneous dose distribution within each
      organ. That assumption is significantly violated in most medical-imaging
      procedures. In helical chest CT, for example, superficial organs (e.g. breasts)
      demonstrate a heterogeneous dose distribution, whereas organs on the peripheries
      of the irradiation field (e.g. liver) might possess a discontinuous dose profile.
      Projection radiography and mammography involve an even higher level of organ dose
      heterogeneity spanning up to two orders of magnitude. As such, mean dose or point
      measured dose values do not reflect the maximum energy deposited per unit volume
      of the organ. In this paper, the magnitude of the dose heterogeneity in both CT
      and projection X-ray imaging was reported, using Monte Carlo methods. The lung
      dose demonstrated factors of 1.7 and 2.2 difference between the mean and maximum
      dose for chest CT and radiography, respectively. The corresponding values for the
      liver were 1.9 and 3.5. For mammography and breast tomosynthesis, the difference
      between mean glandular dose and maximum glandular dose was 3.1. Risk models based
      on the mean dose were found to provide a reasonable reflection of cancer risk.
      However, for leukaemia, they were found to significantly under-represent the risk
      when the organ dose distribution is heterogeneous. A systematic study is needed
      to develop a risk model for heterogeneous dose distributions.

PMID- 23118441
TI  - Editorial: Proteostenosis: cancer's Achilles heel?

PMID- 23118442
TI  - Editorial: Once more unto the breach, dear friends: CMV reactivates when the
      walls come down.

PMID- 23118443
TI  - Editorial: A clear vision needs some balance.

PMID- 23118446
TI  - Complete nucleotide sequence of avian paramyxovirus type 6 strain JL isolated
      from mallard ducks in China.
AB  - A new strain of avian paramyxovirus type 6 (APMV-6), JL, has been isolated from
      mallard ducks in China, and its complete genome has been sequenced and analyzed.
      This work is the first announced complete genome sequence of APMV-6 from
      mallards.

PMID- 23118445
TI  - Comprehensive genomic analyses associate UGT8 variants with musical ability in a
      Mongolian population.
AB  - BACKGROUND: Musical abilities such as recognising music and singing performance
      serve as means for communication and are instruments in sexual selection.
      Specific regions of the brain have been found to be activated by musical stimuli,
      but these have rarely been extended to the discovery of genes and molecules
      associated with musical ability. METHODS: A total of 1008 individuals from 73
      families were enrolled and a pitch-production accuracy test was applied to
      determine musical ability. To identify genetic loci and variants that contribute
      to musical ability, we conducted family-based linkage and association analyses,
      and incorporated the results with data from exome sequencing and array
      comparative genomic hybridisation analyses. RESULTS: We found significant
      evidence of linkage at 4q23 with the nearest marker D4S2986 (LOD=3.1), whose
      supporting interval overlaps a previous study in Finnish families, and identified
      an intergenic single nucleotide polymorphism (SNP) (rs1251078, p = 8.4 * 10(-17))
      near UGT8, a gene highly expressed in the central nervous system and known to act
      in brain organisation. In addition, a non-synonymous SNP in UGT8 was revealed to
      be highly associated with musical ability (rs4148254, p = 8.0 * 10(-17)), and a
      6.2 kb copy number loss near UGT8 showed a plausible association with musical
      ability (p = 2.9 * 10(-6)). CONCLUSIONS: This study provides new insight into the
      genetics of musical ability, exemplifying a methodology to assign functional
      significance to synonymous and non-coding alleles by integrating multiple
      experimental methods.

PMID- 23118448
TI  - Complete genome analysis of three live attenuated Rinderpest virus vaccine
      strains derived through serial passages in different culture systems.
AB  - The genomes of three South Korean Rinderpest virus vaccine strains (L72, LA77,
      and LA96) were analyzed in order to investigate their genetic variability. These
      three vaccine strains were all derived from the same virus strain origin (Fusan)
      through repeated passages in different culture systems. The full genome length of
      the three strains was 15,882 nucleotides, and the sequence similarity between the
      three South Korean RPV strains at the nucleotide level was 98.1 to 98.9%. The
      genetic distance between Nakamura III, L72, LA77, LA96, and LATC06 and the Kabete
      strain was greater than that between the Fusan and Kabete strains for the P, V,
      and C genes. The difference in pathogenicity among these strains might be due to
      the V gene, which has a positive (>1) selection ratio based on the analysis of
      synonymous (dS) and nonsynonymous (dN) substitution rates (dN/dS ratio [omega]).

PMID- 23118447
TI  - Complete genome sequence of a velogenic neurotropic avian paramyxovirus 1
      isolated from peacocks (Pavo cristatus) in a wildlife park in Pakistan.
AB  - Avian paramyxovirus serotype 1 (APMV-1) was isolated from an acute and highly
      contagious outbreak in peacocks (Pavo cristatus) in a wildlife park in Pakistan.
      A velogenic neurotropic form of APMV-1 caused a 100% case fatality rate and
      killed 190 peacocks within a week. Biological and serological characterizations
      showed features of a velogenic strain of APMV-1, and these results were further
      confirmed by sequence analysis of the cleavage site in the fusion protein. The
      complete genome of one of the isolates was sequenced, and phylogenetic analysis
      was conducted. The analysis showed that this isolate belonged to genotype VII,
      specifically, to subgenotype VIIa, and clustered closely with isolates
      characterized from Indonesia in the 1990s. Interestingly, the isolate showed
      significant differences from previously characterized APMV-1 isolates from
      commercial and rural chickens in Pakistan. The work presented here is the first
      complete genome sequence of any APMV-1 isolate from wild birds in the region and
      therefore highlights the need for increased awareness and surveillance in such
      bird species.

PMID- 23118449
TI  - Complete genome sequence of the novel Escherichia coli phage phAPEC8.
AB  - Bacteriophage phAPEC8 is an Escherichia coli-infecting myovirus, isolated on an
      avian pathogenic Escherichia coli (APEC) strain. APEC strains cause
      colibacillosis in poultry, resulting in high mortality levels and important
      economic losses. Genomic analysis of the 147,737-bp double-stranded DNA phAPEC8
      genome revealed that 53% of the 269 encoded proteins are unique to this phage.
      Its closest relatives include the Salmonella phage PVP-SE1 and the coliphage rv5,
      with 19% and 18% similar proteins, respectively. As such, phAPEC8 represents a
      novel, phylogenetically distinct clade within the Myoviridae, with molecular
      properties suitable for phage therapy applications.

PMID- 23118444
TI  - AMP-activated protein kinase and ATP-citrate lyase are two distinct molecular
      targets for ETC-1002, a novel small molecule regulator of lipid and carbohydrate
      metabolism.
AB  - ETC-1002 (8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid) is a novel
      investigational drug being developed for the treatment of dyslipidemia and other
      cardio-metabolic risk factors. The hypolipidemic, anti-atherosclerotic, anti
      obesity, and glucose-lowering properties of ETC-1002, characterized in
      preclinical disease models, are believed to be due to dual inhibition of sterol
      and fatty acid synthesis and enhanced mitochondrial long-chain fatty acid beta
      oxidation. However, the molecular mechanism(s) mediating these activities
      remained undefined. Studies described here show that ETC-1002 free acid activates
      AMP-activated protein kinase in a Ca(2+)/calmodulin-dependent kinase beta
      independent and liver kinase beta 1-dependent manner, without detectable changes
      in adenylate energy charge. Furthermore, ETC-1002 is shown to rapidly form a CoA
      thioester in liver, which directly inhibits ATP-citrate lyase. These distinct
      molecular mechanisms are complementary in their beneficial effects on lipid and
      carbohydrate metabolism in vitro and in vivo. Consistent with these mechanisms,
      ETC-1002 treatment reduced circulating proatherogenic lipoproteins, hepatic
      lipids, and body weight in a hamster model of hyperlipidemia, and it reduced body
      weight and improved glycemic control in a mouse model of diet-induced obesity.
      ETC-1002 offers promise as a novel therapeutic approach to improve multiple risk
      factors associated with metabolic syndrome and benefit patients with
      cardiovascular disease.

PMID- 23118450
TI  - Complete genome sequence of duck Tembusu virus, isolated from Muscovy ducks in
      southern China.
AB  - We report here the complete genomic sequence of the duck Tembusu virus (DTMUV) WJ
      1 strain, isolated from Muscovy ducks. This is the first complete genome sequence
      of DTMUV reported in southern China. Compared with the other strains (TA, GH-2,
      YY5, and ZJ-407) that were previously found in eastern China, WJ-1 bears a few
      differences in the nucleotide and amino acid sequences. We found that there are
      47 mutations of amino acids encoded by the whole open reading frame (ORF) among
      these five strains. The whole-genome sequence of DTMUV will help in understanding
      the epidemiology and molecular characteristics of duck Tembusu virus in southern
      China.

PMID- 23118451
TI  - In vitro and in vivo isolation of a novel rearranged porcine circovirus type 2.
AB  - Here, we present the first report of a novel rearranged porcine circovirus type 2
      (PCV2) strain named BIV, isolated from both in vitro and in vivo sources. The
      complete circular genome of BIV is 896 nucleotides in length. The data will help
      us to update current knowledge of the replication of PCV2 viruses in cell culture
      and of their molecular evolution, as well as their diagnosis.

PMID- 23118452
TI  - Complete genome sequence of a novel highly pathogenic porcine reproductive and
      respiratory syndrome virus variant.
AB  - Highly pathogenic porcine reproductive and respiratory syndrome (HP-PRRS) emerged
      in China in 2006, and HP-PRRS virus (HP-PRRSV) has evolved continuously. Here,
      the complete genomic sequence of a novel HP-PRRSV field strain, JX, is reported.
      The present finding will contribute to further studies focusing on the
      evolutionary mechanism of PRRSV.

PMID- 23118453
TI  - Full genome sequence of bluetongue virus serotype 4 from China.
AB  - The complete genomic sequence of a bluetongue virus serotype 4 (BTV-4) strain
      (strain YTS-4), isolated from sentinel cattle in Yunnan Province, China, is
      reported here. This work is the first to document the complete genomic sequence
      of a BTV-4 strain from China. The sequence information will help determine the
      geographic origin of Chinese BTV-4 and provide data to facilitate future analyses
      of the genetic diversity and phylogenetic relationships of BTV strains.

PMID- 23118454
TI  - Complete genome sequence of hepatitis E virus from rabbits in the United States.
AB  - Hepatitis E virus (HEV) is a single-strand positive-sense RNA virus in the family
      Hepeviridae. The disease caused by HEV, hepatitis E, is an important public
      health problem in developing countries of Asia and Africa and is also endemic in
      many industrialized countries, including the United States. HEV has been
      identified from several other animal species in addition to humans, including the
      pig, chicken, mongoose, deer, rabbit, ferret, bat, and fish. Here we report the
      complete genome sequence of the first strain of HEV from rabbits in the United
      States. Sequence and phylogenetic analyses revealed that the U.S. rabbit HEV is a
      distant member of the zoonotic genotype 3 HEV, thus raising a concern for
      potential zoonotic human infection. A unique 90-nucleotide insertion within the X
      domain of the ORF1 was identified in the rabbit HEV, and this insertion may play
      a role in the species tropism of HEV.

PMID- 23118455
TI  - Complete genome sequence of a newly identified porcine astrovirus genotype 3
      strain US-MO123.
AB  - Astrovirus (AstV) infections are among the most common causes of gastroenteritis
      and are also associated with extraintestinal manifestations in humans and many
      animals. Herein, for the first time, the complete genome sequence of newly
      identified porcine astrovirus genotype 3 (PAstV3) strain US-MO123 was determined.
      Sequence comparison and phylogenetic analysis showed that PAstV3 has the closest
      relationship with mink AstV and the human AstV strains VA1, VA2, and SG,
      indicating the same ancestral origin and zoonotic potential of the virus.

PMID- 23118456
TI  - Pseudoplusia includens densovirus genome organization and expression strategy.
AB  - The genome of a densovirus of a major phytophagous pest, Pseudoplusia includens,
      was analyzed. It contained 5,990 nucleotides (nt) and included inverted terminal
      repeats of 540 nt with terminal Y-shaped hairpins of 120 nt. Its DNA sequence and
      ambisense organization with 4 typical open reading frames demonstrated that it
      belonged to the genus Densovirus in the subfamily Densovirinae of the family
      Parvoviridae.

PMID- 23118457
TI  - Complete genome sequence of an enterovirus 80 strain isolated in China.
AB  - Enterovirus 80 (EV80) is a newly identified serotype of the species Human
      enterovirus B. An EV80 strain designated HZ01/SD/CHN/2004 was isolated from an
      acute flaccid paralysis case in Shandong, China, in 2004. Complete genome
      comparison revealed 79.5% similarity with the prototype strain and an insertion
      of 36 nucleotides in the 3' end of the VP1 coding region. Intertypic
      recombination with other serotypes was observed. This is the first report of the
      complete genome of EV80 in China.

PMID- 23118458
TI  - Complete genome sequence of bacteriophage phiAC-1 infecting Acinetobacter soli
      strain KZ-1.
AB  - To date, a number of bacteriophages (phages) infecting Acinetobacter species have
      been reported and characterized. However, Acinetobacter phages which infect A.
      soli have not been investigated yet. Here, we report the complete genome sequence
      of Acinetobacter phage phiAC-1, which belongs to the Myoviridae, infecting
      Acinetobacter soli strain KZ-1.

PMID- 23118459
TI  - Genome sequence of a monoreassortant H1N1 swine influenza virus isolated from a
      pig in Hungary.
AB  - The genome of a porcine H1N1 influenza A strain is reported in this study. The
      strain proved to be a monoreassortant strain with a typical porcine N1 gene on
      the genetic backbone of the pandemic H1N1 influenza A virus strain. Monitoring of
      descendants of the pandemic 2009 H1N1 strain is needed because of concerns that
      more-virulent strains may emerge in forthcoming epidemic seasons.

PMID- 23118460
TI  - Complete genome sequence of a coxsackievirus B3 isolated from a Sichuan snub
      nosed monkey.
AB  - Coxsackievirus B3 (CVB3) is an enterovirus in the family Picornaviridae that is
      significant to human health, being associated with myocarditis, aseptic
      meningitis, and pancreatitis, among other conditions. In addition to humans,
      Sichuan snub-nosed monkeys can be infected and killed by CVB3. Here, we report
      the first complete genome sequence of a novel coxsackievirus B3 strain, SSM-CVB3,
      which was isolated from a deceased Sichuan snub-nosed monkey with severe
      myocarditis. Our findings may aid in understanding the evolutionary
      characteristics and molecular pathogenesis of this virus.

PMID- 23118461
TI  - Complete genome sequence analysis of a duck circovirus from Guangxi pockmark
      ducks.
AB  - We report here the complete genomic sequence of a novel duck circovirus (DuCV)
      strain, GX1104, isolated from Guangxi pockmark ducks in Guangxi, China. The whole
      nucleotide sequence had the highest homology (97.2%) with the sequence of strain
      TC/2002 (GenBank accession number AY394721.1) and had a low homology (76.8% to
      78.6%) with the sequences of other strains isolated from China, Germany, and the
      United States. This report will help to understand the epidemiology and molecular
      characteristics of Guangxi pockmark duck circovirus in southern China.

PMID- 23118462
TI  - Complete genomic sequence of a reovirus isolate from Pekin ducklings in China.
AB  - The complete genomic sequence of a Pekin duck origin reovirus (DRV) from China
      was determined. The genome comprises 23,419 bp, with segments ranging from 1,191
      bp (S4) to 3,959 bp (L1). Pairwise comparisons and phylogenetic analysis indicate
      that the Pekin duck origin reovirus is more closely related to the new type of
      Muscovy duck origin reovirus (N-MDRV) identified recently than to the chicken
      origin avian orthoreovirus (ARV) and the originally described Muscovy duck origin
      reovirus (ARV-Md).

PMID- 23118463
TI  - Complete genome sequence of Vibrio parahaemolyticus bacteriophage vB_VpaM_MAR.
AB  - Vibrio parahaemolyticus is a major pathogen that is mainly associated with
      seafood and is a global food safety issue. Our objective was to isolate and
      completely sequence a specific phage against this bacterium. Phage vB_VpaM_MAR is
      able to lyse 76% of the V. parahaemolyticus strains tested. MAR belongs to the
      Myoviridae family and has a genome comprised of double-stranded DNA with a size
      of 41,351 bp, a G+C content of 51.3%, and 62 open reading frames (ORFs).
      Bioinformatic analysis showed that phage MAR is closely related to Vibrio phages
      VHML, VP58.5, and VP882 and Halomonas aquamarina phage PhiHAP-1.

PMID- 23118464
TI  - Complete genomic sequence of a Muscovy duck-origin reticuloendotheliosis virus
      from China.
AB  - The complete proviral sequence of a Muscovy duck-origin reticuloendotheliosis
      virus (REV) associated with spontaneously occurring neoplastic disease in 2011 in
      Zhejiang province, China, was determined. Comparative sequence analyses indicate
      that the present REV is most closely related to the chicken-origin REV isolate
      HLJR0901 and the goose-origin isolate Goose/3410/06. These findings suggest that
      chickens or geese may transmit the REV to Muscovy ducks.

PMID- 23118465
TI  - Complete genome of a novel endornavirus assembled from next-generation sequence
      data.
AB  - Endornaviruses have large double-stranded RNA (dsRNA) genomes that carry a single
      open reading frame (ORF). Here we report the complete genome of a novel
      endornavirus, assembled from next-generation sequence data generated from Vitis
      vinifera-extracted dsRNA. Two different fungal hosts have been identified for
      this virus, suggesting that horizontal transmission of the virus is possible.

PMID- 23118466
TI  - Proteomic analysis of protease resistant proteins in the diabetic rat kidney.
AB  - Glycation induced protein aggregation has been implicated in the development of
      diabetic complications and neurodegenerative diseases. These aggregates are known
      to be resistant to proteolytic digestion. Here we report the identification of
      protease resistant proteins from the streptozotocin induced diabetic rat kidney,
      which included enzymes in glucose metabolism and stress response proteins. These
      protease resistant proteins were characterized to be advanced glycation end
      products modified and ubiquitinated by immunological and mass spectrometry
      analysis. Further, diabetic rat kidney exhibited significantly impaired
      proteasomal activity. The functional analysis of identified physiologically
      important enzymes showed that their activity was reduced in diabetic condition.
      Loss of functional activity of these proteins was compensated by enhanced gene
      expression. Aggregation prone regions were predicted by in silico analysis and
      compared with advanced glycation end products modification sites. These findings
      suggested that the accumulation of protein aggregates is an inevitable
      consequence of impaired proteasomal activity and protease resistance due to
      advanced glycation end products modification.

PMID- 23118467
TI  - Getting the justification for research ethics review right.
AB  - Dyck and Allen claim that the current model for mandatory ethical review of
      research involving human participants is unethical once the harms that accrue
      from the review process are identified. However, the assumptions upon which the
      authors assert that this model of research ethics governance is justified are
      false. In this commentary, I aim to correct these assumptions, and provide the
      right justificatory account of the requirement for research ethics review. This
      account clarifies why the subsequent arguments that Dyck and Allen make in the
      paper lack force, and why the 'governance problem' in research ethics that they
      allude to ought to be explained differently. 

PMID- 23118468
TI  - Unrealistic optimism and the ethics of phase I cancer research.
AB  - One of the most pressing ethical challenges facing phase I cancer research
      centres is the process of informed consent. Historically, most scholarship has
      been devoted to redressing therapeutic misconception, that is, the conflation of
      the nature and goals of research with those of therapy. While therapeutic
      misconception continues to be a major ethical concern, recent scholarship has
      begun to recognise that the informed consent process is more complex than merely
      a transfer of information and therefore cannot be evaluated only according to how
      well an individual understands such information. Other components of decision
      making operate independently of understanding and yet still may compromise the
      quality of informed consent. Notable among these components is unrealistic
      optimism, an event-specific belief that one has a better chance of receiving
      benefit than others similarly situated. In this article, we consider responses to
      interviews with parents who had recently completed an informed consent conference
      for enrolling their child in a phase I cancer clinical trial to examine how this
      influence manifests and how investigators might address it during informed
      consent.

PMID- 23118469
TI  - Ethics policy review: a case study in quality improvement.
AB  - Policy work is often cited as one of the primary functions of Hospital Ethics
      Committees (HECs), along with consultation and education. Hospital policies can
      have far reaching effects on a wide array of stakeholders including, care
      providers, patients, families, the culture of the organisation and the community
      at large. In comparison with the wealth of information available about the
      emerging practice of ethics consultation, relatively little attention has been
      paid to the policy work of HECs. In this paper, we hope to advance the
      development of best practices in HEC policy work by describing the quality
      improvement process that we undertook at Hamilton Health Sciences, Hamilton,
      Ontario, Canada. In the first section of the paper we describe the context of our
      HEC policy work, and the shortcomings of our historical review process. In
      subsequent sections, we detail the quality improvement project we undertook in
      2010, the results of the project and the specific tools we developed to enhance
      the quality of HEC policy work. Our goal in sharing this organisational case
      study is to prompt other HECs to publish qualitative descriptions of their policy
      work, in order to generate a body of knowledge that can inform the development of
      best practices for ethics policy review.

PMID- 23118470
TI  - Realising social justice in public health law.
AB  - Law has played an important, but largely constitutive, role in the development of
      the public health enterprise. Thus, law has been central to setting up the
      institutions and offices of public health. The moral agenda has, however, been
      shaped to a much greater extent by bioethics. While social justice has been
      placed at the heart of this agenda, we argue that there has been little place
      within dominant conceptions of social justice for gender equity and women's
      interests which we see as crucial to a fully realised vision of social justice.
      We argue that, aside from particular interventions in the field of reproduction,
      public health practice tends to marginalise women-a claim we support by
      critically examining strategies to combat the HIV pandemic in sub-Saharan Africa.
      To counter the marginalisation of women's interests, this article argues that
      Amartya Sen's capabilities approach has much to contribute to the framing of
      public health law and policy. Sen's approach provides an evaluative and normative
      framework which recognises the importance of both gender and health equity to
      achieving social justice. We suggest that domestic law and international human
      rights provisions, in particular the emerging human right to health, offer
      mechanisms to promote capabilities, and foster a robust and inclusive conception
      of social justice.

PMID- 23118471
TI  - Relying on common law defences to legalise assisted dying: problems and
      possibilities.

PMID- 23118472
TI  - 1-alkyl-(N,N-dimethylamino)pyridinium bromides: inhibitory effect on virulence
      factors of Candida albicans and on the growth of bacterial pathogens.
AB  - A homologous series of 1-alkyl-(N,N-dimethylamino)pyridinium bromides, termed
      compounds 1-11, was synthesized and studied for antibacterial and antifungal
      activity. Of these, compound 8, containing a ten-carbon alkyl chain, showed
      maximum inhibition against all the tested bacterial strains. The highest
      antibacterial activity using a disc diffusion method was recorded against
      Mycobacterium smegmatis [zone of inhibition (ZOI): 45.75+/-0.25 mm], followed by
      Escherichia coli, Proteus mirabilis, Vibrio cholerae, Staphylococcus aureus and
      Salmonella typhi. In addition to antibacterial activity, compounds 3-11 displayed
      good inhibitory action against the human opportunistic yeast pathogens
      Cryptococcus neoformans and various Candida spp. The maximum ZOI was observed
      against Cryptococcus neoformans (51.5+/-0.5 mm) using compound 8, with ZOIs of
      23.5+/-0.5, 32.0+/-0.0, 27.75+/-0.25 and 41.5+/-0.5 mm against Candida albicans,
      Candida glabrata, Candida tropicalis and Candida krusei, respectively.
      Furthermore, compound 8 caused inhibition of the candidal yeast-hyphae transition
      at a concentration of 0.29 uM and also inhibited the secretion of extracellular
      hydrolytic enzyme such as secreted aspartyl proteinase at subinhibitory
      concentrations. Compound 8 showed very little haemolytic activity at a
      concentration of 0.58 uM (1.315+/-0.75 %), with its highest haemolytic activity
      (47.806+/-2.32 %) observed at a concentration of 2.9 uM.

PMID- 23118473
TI  - Bartonella henselae infection in a man with hypergammaglobulinaemia, splenomegaly
      and polyclonal plasmacytosis.
AB  - Bartonella henselae is an infrequently reported cause of polyclonal plasmacytosis
      and hypergammaglobulinaemia. We herein document B. henselae infection in a 66
      year-old patient who presented with hypergammaglobulinaemia, splenomegaly with
      polyclonal plasmacytosis, stroke, and suspected prosthetic aortic arch infection.
      Clinicians should remain cognizant of the heterogeneous clinical presentations
      associated with bartonellosis.

PMID- 23118474
TI  - Phenotypic and molecular characterization of Staphylococcus aureus recovered from
      different clinical specimens of inpatients at a teaching hospital in Shanghai
      between 2005 and 2010.
AB  - Staphylococcus aureus, including meticillin-sensitive and -resistant S. aureus
      (MSSA and MRSA, respectively), is associated with severe nosocomial human
      infections. This study aimed to investigate the molecular profile, including the
      dynamic changes and genotype/phenotype correlation, of S. aureus isolates
      recovered from different clinical specimens of inpatients with S. aureus
      infection over a 6-year span at a teaching hospital in Shanghai, China. Between
      2005 and 2010, a random sample of 610 unique S. aureus isolates was collected
      from different clinical samples of inpatients with S. aureus infection for
      molecular and antibiotic susceptibility analysis. The results showed that, among
      the 610 S. aureus isolates, 20 sequence types (STs) determined by multi-locus
      sequence typing (primarily ST239, ST5, ST7, ST188 and ST398) and 52 spa types
      (primarily t002, t037, t030 and t601) were found. In total, 444 isolates (72.8 %)
      were MRSA and 166 (27.2 %) were MSSA. ST239-MRSA-III-spa t037 and ST5-MRSA-II-spa
      t002 were the predominant MRSA clones. From 2005 to 2010, spa t002, spa t037 and
      their corresponding STs (ST5 and ST239) were the most frequent clones among all
      of the S. aureus isolates and showed the most resistant phenotypes to various
      antibiotics. Generally, the different genotypes showed different drug resistance
      rates, but no isolates were resistant to vancomycin, teicoplanin or linezolid.
      The profiles of virulence and resistance genes differed by genetic background,
      with the ST239 and ST5 strains showing higher resistance rates to gentamicin,
      cefoxitin, ampicillin, cefazolin, erythromycin, clindamycin and levofloxacin than
      strains of other types. Moreover, the antiseptic resistance genes qacA/B were
      generally associated with these two types. The prevalence of STs was different
      among different clinical specimens and also changed by year. Recently (2009
      2010), the distribution of predominant MRSA clones decreased, whilst the
      prevalence of non-predominant MSSA clones increased, especially for the isolates
      causing bacteraemia. Continual monitoring of clinical isolates is necessary to
      develop and maintain an effective strategy against S. aureus infection in the
      hospital setting.

PMID- 23118475
TI  - Identification of blaLAP-2 and qnrS1 genes in the internationally successful
      Klebsiella pneumoniae ST147 clone.
AB  - We investigated the presence of beta-lactamase genes (bla) in 26 strains of
      Enterobacteriaceae already found positive for the qnrS1 gene, a plasmid-mediated
      quinolone resistance determinant. Three strains of K. pneumoniae, isolated in the
      period 2008-2009 at the University Hospital in Verona, were positive for LAP-2, a
      narrow-spectrum beta-lactamase. These strains, namely VRB586, VRE185 and VRE196,
      were cultured from urine, bile and peritoneal drainage, respectively, of
      different patients from different units. The bla(LAP-2) and qnrS1 resistance
      determinant genes were separated by ISEcl2 and were located on a 97 kb conjugable
      and untypable plasmid, which could be transferred to a recipient strain, E. coli
      J53. The fluoroquinolone and ceftazidime MICs increased 1-2-fold in the
      transconjugant cells. The three K. pneumoniae strains were found to be clonal by
      PFGE and were identified as belonging to ST147, an internationally successful
      clone, by MLST. The plasmid sequence, including ISEcl2 and qnrS1 genes, of K.
      pneumoniae ST147 was found to be highly similar to previously detected qnrS1
      harbouring plasmids, suggesting the plasmid has a stable genetic structure and
      that these resistance determinants have a common source. To the best of our
      knowledge, this is the first report of the internationally successful K.
      pneumoniae ST147 strain carrying bla(LAP-2) and qnrS1 genes and is the first case
      of LAP beta-lactamase in Italy.

PMID- 23118476
TI  - Swabs (dry or collected in universal transport medium) and semen can be used for
      the detection of Chlamydia trachomatis using the cobas 4800 system.
AB  - In this prospective study, the fully automated cobas 4800 CT/NG and the cobas
      TaqMan CT tests were compared for Chlamydia trachomatis detection in urine and in
      genital specimens collected with Copan flocked swabs in culture media. A protocol
      was also established for the highly sensitive detection of C. trachomatis in
      semen specimens using the cobas 4800 CT/NG test. A total of 708 consecutive
      urogenital samples (293 male urine samples and 356 vaginal, 45 cervical and 14
      urethral swabs) obtained from the Bacteriology Department, as well as 100
      consecutive semen samples collected from patients attending the Reproduction
      Biology Department, Bordeaux University Hospital, France, from July to September
      2010, were analysed. Positive and negative agreements between the cobas 4800
      CT/NG and cobas TaqMan CT tests were 92.7 % [95 % confidence interval (CI), 82.7
      97.1 %] and 99.2 % (95 % CI, 98.2-99.7 %), respectively, with an overall
      agreement of 98.7 % (699/708). The clinical sensitivity of the cobas 4800 CT/NG
      assay for C. trachomatis ranged from 90.9 to 100 % depending on specimen type,
      with an overall prevalence of 7.2 % (51/708). The clinical specificity ranged
      from 99.1 to 100 % depending on specimen type. Dilution of 25 ul semen samples in
      cobas PCR medium proved to be the most sensitive protocol with the lowest
      inhibition rate. In conclusion, the cobas 4800 CT/NG test was found to be an
      effective method for detection of C. trachomatis in semen, male urine and genital
      swab samples collected dry or in universal transport medium.

PMID- 23118477
TI  - Arabidopsis ROP1 and ROP6 influence germination time, root morphology, the
      formation of F-actin bundles, and symbiotic fungal interactions.
AB  - The RHO-related GTPases ROP1 and ROP6 and the ROP1-interacting protein RIC4 in
      Arabidopsis are involved in various processes of F-actin dynamics, cell growth,
      and plant/microbe interactions. The knockout rop1 and rop1 rop6 seeds germinate
      earlier and are impaired in root hair development. Also root hair branching is
      strongly affected by manipulation of the RHO-related GTPase (ROP) levels.
      Furthermore, in the double knockout line rop1 rop6, no actin bundle formation can
      be detected. We demonstrate that these proteins are required for establishing a
      mutualistic interaction between the root-colonizing endophytic fungus
      Piriformospora indica and Arabidopsis. The fungus promotes growth of wild-type
      plants. rop1, rop6, rop1 rop6, ric4, 35S::ROP1, and 35S::ROP6 seedlings are
      impaired in the response to the fungus. Since the different root architectures
      have no effect on root colonization, the impaired response to P. indica should be
      caused by ROP-mediated events in the root cells. In wild-type roots, P. indica
      stimulates the formation of F-actin bundles and this does not occur in the rop1
      rop6 knockout line. Furthermore, the fungus stimulates the expression of the
      calmodulin-binding protein gene Cbp60g, and this response is severely reduced in
      the rop mutants. We propose that ROP1 and ROP6 are required for F-actin bundle
      formation in the roots, which is required for P. indica-mediated growth promotion
      in Arabidopsis.

PMID- 23118478
TI  - An approach to quantify endomembrane dynamics in pollen utilizing bioactive
      chemicals.
AB  - Tip growth of pollen tubes and root hairs occurs via rapid polar growth. These
      rapidly elongating cells require tip-focused endomembrane trafficking for the
      deposition and recycling of proteins, membranes, and cell wall materials. Most of
      the image-based data published to date are subjective and non-quantified.
      Quantitative and comparative descriptors of these highly dynamic processes have
      been a major challenge, but are highly desirable for genetic and chemical
      genomics approaches to dissect this biological network. To address this problem,
      we screened for small molecules that perturbed the localization of a marker for
      the Golgi Ras-like monomeric G-protein RAB2:GFP expressed in transgenic tobacco
      pollen. Semi-automated high-throughput imaging and image analysis resulted in the
      identification of novel compounds that altered pollen tube development and
      endomembrane trafficking. Six compounds that caused mislocalization and varying
      degrees of altered movement of RAB2:GFP-labeled endomembrane bodies were used to
      generate a training set of image data from which to quantify vesicle dynamics.
      The area, velocity, straightness, and intensity of each body were quantified
      using semi-automated image analysis tools revealing quantitative differences in
      the phenotype caused by each compound. A score was then given to each compound
      enabling quantitative comparisons between compounds. Our results demonstrate that
      image analysis can be used to quantitatively evaluate dynamic subcellular
      endomembrane phenotypes induced by bioactive chemicals, mutations, or other
      perturbing agents as part of a strategy to quantitatively dissect the
      endomembrane network. 

PMID- 23118479
TI  - SpliceAid-F: a database of human splicing factors and their RNA-binding sites.
AB  - A comprehensive knowledge of all the factors involved in splicing, both proteins
      and RNAs, and of their interaction network is crucial for reaching a better
      understanding of this process and its functions. A large part of relevant
      information is buried in the literature or collected in various different
      databases. By hand-curated screenings of literature and databases, we retrieved
      experimentally validated data on 71 human RNA-binding splicing regulatory
      proteins and organized them into a database called 'SpliceAid-F'
      (http://www.caspur.it/SpliceAidF/). For each splicing factor (SF), the database
      reports its functional domains, its protein and chemical interactors and its
      expression data. Furthermore, we collected experimentally validated RNA-SF
      interactions, including relevant information on the RNA-binding sites, such as
      the genes where these sites lie, their genomic coordinates, the splicing effects,
      the experimental procedures used, as well as the corresponding bibliographic
      references. We also collected information from experiments showing no RNA-SF
      binding, at least in the assayed conditions. In total, SpliceAid-F contains 4227
      interactions, 2590 RNA-binding sites and 1141 'no-binding' sites, including
      information on cellular contexts and conditions where binding was tested. The
      data collected in SpliceAid-F can provide significant information to explain an
      observed splicing pattern as well as the effect of mutations in functional
      regulatory elements.

PMID- 23118480
TI  - The nuclease domain of the SPP1 packaging motor coordinates DNA cleavage and
      encapsidation.
AB  - The large terminase subunit is a central component of the genome packaging motor
      from tailed bacteriophages and herpes viruses. This two-domain enzyme has an N
      terminal ATPase activity that fuels DNA translocation during packaging and a C
      terminal nuclease activity required for initiation and termination of the
      packaging cycle. Here, we report that bacteriophage SPP1 large terminase (gp2) is
      a metal-dependent nuclease whose stability and activity are strongly and
      preferentially enhanced by Mn(2+) ions. Mutation of conserved residues that
      coordinate Mn(2+) ions in the nuclease catalytic site affect the metal-induced
      gp2 stabilization and impair both gp2-specific cleavage at the packaging
      initiation site pac and unspecific nuclease activity. Several of these mutations
      block also DNA encapsidation without affecting ATP hydrolysis or gp2 C-terminus
      binding to the procapsid portal vertex. The data are consistent with a mechanism
      in which the nuclease domain bound to the portal switches between nuclease
      activity and a coordinated action with the ATPase domain for DNA translocation.
      This switch of activities of the nuclease domain is critical to achieve the viral
      chromosome packaging cycle.

PMID- 23118481
TI  - Silencing of human DNA polymerase lambda causes replication stress and is
      synthetically lethal with an impaired S phase checkpoint.
AB  - Human DNA polymerase (pol) lambda functions in base excision repair and non
      homologous end joining. We have previously shown that DNA pol lambda is involved
      in accurate bypass of the two frequent oxidative lesions, 7,8-dihydro-8
      oxoguanine and 1,2-dihydro-2-oxoadenine during the S phase. However, nothing is
      known so far about the relationship of DNA pol lambda with the S phase DNA damage
      response checkpoint. Here, we show that a knockdown of DNA pol lambda, but not of
      its close homologue DNA pol beta, results in replication fork stress and
      activates the S phase checkpoint, slowing S phase progression in different human
      cancer cell lines. We furthermore show that DNA pol lambda protects cells from
      oxidative DNA damage and also functions in rescuing stalled replication forks.
      Its absence becomes lethal for a cell when a functional checkpoint is missing,
      suggesting a DNA synthesis deficiency. Our results provide the first evidence, to
      our knowledge, that DNA pol lambda is required for cell cycle progression and is
      functionally connected to the S phase DNA damage response machinery in cancer
      cells.

PMID- 23118482
TI  - Mechanism of RNA 2',3'-cyclic phosphate end healing by T4 polynucleotide kinase
      phosphatase.
AB  - T4 polynucleotide kinase-phosphatase (Pnkp) exemplifies a family of enzymes with
      5'-kinase and 3'-phosphatase activities that function in nucleic acid repair. The
      polynucleotide 3'-phosphatase reaction is executed by the Pnkp C-terminal domain,
      which belongs to the DxDxT acylphosphatase superfamily. The 3'-phosphatase
      reaction entails formation and hydrolysis of a covalent enzyme-(Asp165)-phosphate
      intermediate, driven by general acid-base catalyst Asp167. We report that Pnkp
      also has RNA 2'-phosphatase activity that requires Asp165 and Asp167. The
      physiological substrate for Pnkp phosphatase is an RNA 2',3'-cyclic phosphate end
      (RNA > p), but the pathway of cyclic phosphate removal and its enzymic
      requirements are undefined. Here we find that Pnkp reactivity with RNA > p
      requires Asp165, but not Asp167. Whereas wild-type Pnkp transforms RNA > p to
      RNA(OH), mutant D167N converts RNA > p to RNA 3'-phosphate, which it sequesters
      in the phosphatase active site. In support of the intermediacy of an RNA
      phosphomonoester, the reaction of mutant S211A with RNA > p results in transient
      accumulation of RNAp en route to RNA(OH). Our results suggest that healing of
      2',3'-cyclic phosphate ends is a four-step processive reaction: RNA > p + Pnkp ->
      RNA-(3'-phosphoaspartyl)-Pnkp -> RNA(3')p + Pnkp -> RNA(OH) + phosphoaspartyl
      Pnkp -> P(i) + Pnkp.

PMID- 23118485
TI  - MBGD update 2013: the microbial genome database for exploring the diversity of
      microbial world.
AB  - The microbial genome database for comparative analysis (MBGD, available at
      http://mbgd.genome.ad.jp/) is a platform for microbial genome comparison based on
      orthology analysis. As its unique feature, MBGD allows users to conduct orthology
      analysis among any specified set of organisms; this flexibility allows MBGD to
      adapt to a variety of microbial genomic study. Reflecting the huge diversity of
      microbial world, the number of microbial genome projects now becomes several
      thousands. To efficiently explore the diversity of the entire microbial genomic
      data, MBGD now provides summary pages for pre-calculated ortholog tables among
      various taxonomic groups. For some closely related taxa, MBGD also provides the
      conserved synteny information (core genome alignment) pre-calculated using the
      CoreAligner program. In addition, efficient incremental updating procedure can
      create extended ortholog table by adding additional genomes to the default
      ortholog table generated from the representative set of genomes. Combining with
      the functionalities of the dynamic orthology calculation of any specified set of
      organisms, MBGD is an efficient and flexible tool for exploring the microbial
      genome diversity.

PMID- 23118483
TI  - Spliceosome database: a tool for tracking components of the spliceosome.
AB  - The spliceosome is the extremely complex macromolecular machine responsible for
      pre-mRNA splicing. It assembles from five U-rich small nuclear RNAs (snRNAs) and
      over 200 proteins in a highly dynamic fashion. One important challenge to
      studying the spliceosome is simply keeping track of all these proteins, a
      situation further complicated by the variety of names and identifiers that exist
      in the literature for them. To facilitate studies of the spliceosome and its
      components, we created a database of spliceosome-associated proteins and snRNAs,
      which is available at http://spliceosomedb.ucsc.edu and can be queried through a
      simple browser interface. In the database, we cataloged the various names,
      orthologs and gene identifiers of spliceosome proteins to navigate the complex
      nomenclature of spliceosome proteins. We also provide links to gene and protein
      records for the spliceosome components in other databases. To navigate
      spliceosome assembly dynamics, we created tools to compare the association of
      spliceosome proteins with complexes that form at specific stages of spliceosome
      assembly based on a compendium of mass spectrometry experiments that identified
      proteins in purified splicing complexes. Together, the information in the
      database provides an easy reference for spliceosome components and will support
      future modeling of spliceosome structure and dynamics.

PMID- 23118484
TI  - MODOMICS: a database of RNA modification pathways--2013 update.
AB  - MODOMICS is a database of RNA modifications that provides comprehensive
      information concerning the chemical structures of modified ribonucleosides, their
      biosynthetic pathways, RNA-modifying enzymes and location of modified residues in
      RNA sequences. In the current database version, accessible at
      http://modomics.genesilico.pl, we included new features: a census of human and
      yeast snoRNAs involved in RNA-guided RNA modification, a new section covering the
      5'-end capping process, and a catalogue of 'building blocks' for chemical
      synthesis of a large variety of modified nucleosides. The MODOMICS collections of
      RNA modifications, RNA-modifying enzymes and modified RNAs have been also
      updated. A number of newly identified modified ribonucleosides and more than one
      hundred functionally and structurally characterized proteins from various
      organisms have been added. In the RNA sequences section, snRNAs and snoRNAs with
      experimentally mapped modified nucleosides have been added and the current
      collection of rRNA and tRNA sequences has been substantially enlarged. To
      facilitate literature searches, each record in MODOMICS has been cross-referenced
      to other databases and to selected key publications. New options for database
      searching and querying have been implemented, including a BLAST search of protein
      sequences and a PARALIGN search of the collected nucleic acid sequences.

PMID- 23118486
TI  - Structural asymmetry in the Thermus thermophilus RuvC dimer suggests a basis for
      sequential strand cleavages during Holliday junction resolution.
AB  - Holliday junction (HJ) resolvases are structure-specific endonucleases that
      cleave four-way DNA junctions (HJs) generated during DNA recombination and
      repair. Bacterial RuvC, a prototypical HJ resolvase, functions as homodimer and
      nicks DNA strands precisely across the junction point. To gain insights into the
      mechanisms underlying symmetrical strand cleavages by RuvC, we performed
      crystallographic and biochemical analyses of RuvC from Thermus thermophilus
      (T.th. RuvC). The crystal structure of T.th. RuvC shows an overall protein fold
      similar to that of Escherichia coli RuvC, but T.th. RuvC has a more tightly
      associated dimer interface possibly reflecting its thermostability. The binding
      mode of a HJ-DNA substrate can be inferred from the shape/charge complementarity
      between the T.th. RuvC dimer and HJ-DNA, as well as positions of sulfate ions
      bound on the protein surface. Unexpectedly, the structure of T.th. RuvC homodimer
      refined at 1.28 A resolution shows distinct asymmetry near the dimer interface,
      in the region harboring catalytically important aromatic residues. The
      observation suggests that the T.th. RuvC homodimer interconverts between two
      asymmetric conformations, with alternating subunits switched on for DNA strand
      cleavage. This model provides a structural basis for the 'nick-counter-nick'
      mechanism in HJ resolution, a mode of HJ processing shared by prokaryotic and
      eukaryotic HJ resolvases.

PMID- 23118487
TI  - CellLineNavigator: a workbench for cancer cell line analysis.
AB  - The CellLineNavigator database, freely available at
      http://www.medicalgenomics.org/celllinenavigator, is a web-based workbench for
      large scale comparisons of a large collection of diverse cell lines. It aims to
      support experimental design in the fields of genomics, systems biology and
      translational biomedical research. Currently, this compendium holds genome wide
      expression profiles of 317 different cancer cell lines, categorized into 57
      different pathological states and 28 individual tissues. To enlarge the scope of
      CellLineNavigator, the database was furthermore closely linked to commonly used
      bioinformatics databases and knowledge repositories. To ensure easy data access
      and search ability, a simple data and an intuitive querying interface were
      implemented. It allows the user to explore and filter gene expression, focusing
      on pathological or physiological conditions. For a more complex search, the
      advanced query interface may be used to query for (i) differentially expressed
      genes; (ii) pathological or physiological conditions; or (iii) gene names or
      functional attributes, such as Kyoto Encyclopaedia of Genes and Genomes pathway
      maps. These queries may also be combined. Finally, CellLineNavigator allows
      additional advanced analysis of differentially regulated genes by a direct link
      to the Database for Annotation, Visualization and Integrated Discovery (DAVID)
      Bioinformatics Resources.

PMID- 23118488
TI  - HEXEvent: a database of Human EXon splicing Events.
AB  - HEXEvent (http://hexevent.mmg.uci.edu) is a new database that permits the user to
      compile genome-wide exon data sets of human internal exons showing selected
      splicing events. User queries can be customized based on the type and the
      frequency of alternative splicing events. For each splicing version of an exon,
      an ESTs count is given, specifying the frequency of the event. A user-specific
      definition of constitutive exons can be entered to designate an exon exclusion
      level still acceptable for an exon to be considered as constitutive. Similarly,
      the user has the option to define a maximum inclusion level for an exon to be
      called an alternatively spliced exon. Unlike other existing splicing databases,
      HEXEvent permits the user to easily extract alternative splicing information for
      individual, multiple or genome-wide human internal exons. Importantly, the
      generated data sets are downloadable for further analysis.

PMID- 23118490
TI  - Electro-catalytic activity of multiwall carbon nanotube-metal (Pt or Pd)
      nanohybrid materials synthesized using microwave-induced reactions and their
      possible use in fuel cells.
AB  - Microwave induced reactions for immobilizing platinum and palladium nanoparticles
      on multiwall carbon nanotubes are presented. The resulting hybrid materials were
      used as catalysts for direct methanol, ethanol and formic acid oxidation in
      acidic as well as alkaline media. The electrodes are formed by simply mixing the
      hybrids with graphite paste, thus using a relatively small quantity of the
      precious metal. We report Tafel slopes and apparent activation energies at
      different potentials and temperatures. Ethanol electro-oxidation with the
      palladium hybrid showed an activation energy of 7.64 kJmol(-1) which is lower
      than those observed for other systems. This system is economically attractive
      because Pd is significantly less expensive than Pt and ethanol is fast evolving
      as a commercial biofuel.

PMID- 23118489
TI  - Indirect read-out of the promoter DNA by RNA polymerase in the closed complex.
AB  - Transcription is initiated when RNA polymerase recognizes the duplex promoter DNA
      in the closed complex. Due to its transient nature, the closed complex has not
      been well characterized. How the initial promoter recognition occurs may offer
      important clues to regulation of transcription initiation. In this article, we
      have carried out single-base pair substitution experiments on two Escherichia
      coli promoters belonging to two different classes, the -35 and the extended -10,
      under conditions which stabilize the closed complex. Single-base pair
      substitution experiments indicate modest base-specific effects on the stability
      of the closed complex of both promoters. Mutations of base pairs in the -10
      region affect the closed complexes of two promoters differently, suggesting
      different modes of interaction of the RNA polymerase and the promoter in the two
      closed complexes. Two residues on sigma(70) which have been suggested to play
      important role in promoter recognition, Q437 and R436, were mutated and found to
      have different effects on the closed-complex stability. DNA circular dichroism
      (CD) and FRET suggest that the promoter DNA in the closed complex is distorted.
      Modeling suggests two different orientations of the recognition helix of the RNA
      polymerase in the closed complex. We propose that the RNA polymerase recognizes
      the sequence dependent conformation of the promoter DNA in the closed complex.

PMID- 23118491
TI  - First total synthesis of the (+/-)-2-methoxy-6-heptadecynoic acid and related 2
      methoxylated analogs as effective inhibitors of the leishmania topoisomerase IB
      enzyme.
AB  - The fatty acids (+/-)-2-methoxy-6Z-heptadecenoic acid (1), (+/-)-2-methoxy-6
      heptadecynoic acid (2) and (+/-)-2-methoxyheptadecanoic acid (3) were synthesized
      and their inhibitory activity against the Leishmania DNA topoisomerase IB enzyme
      (LdTopIB) determined. Acids 1 and 2 were synthesized from 4-bromo-1-pentanol, the
      former in ten steps and in 7% overall yield, while the latter in seven steps and
      in 14% overall yield. Acid 3 was prepared in six steps and in 42% yield from 1
      hexadecanol. Acids 1-3 inhibited the LdTopIB enzyme following the order 2 > 1 ?
      3, with 2 displaying an EC(50) = 16.6 +/- 1.1 MUM and 3 not inhibiting the
      enzyme. Acid 1 preferentially inhibited the LdTopIB enzyme over the human TopIB
      enzyme. Unsaturation seems to be a prerequisite for effective inhibition,
      rationalized in terms of weak intermolecular interactions between the active site
      of LdTopIB and either the double or triple bonds of the fatty acids. Toxicity
      towards Leishmania donovani promastigotes was also investigated resulting in the
      same order 2 > 1 > 3, with 2 displaying an EC(50) = 74.0 +/- 17.1 MUM. Our
      results indicate that alpha-methoxylation decreases the toxicity of C(17:1) fatty
      acids towards L. donovani promastigotes, but improves their selectivity index.

PMID- 23118493
TI  - Methods for Optimal Intervention in Gene Regulatory Networks.

PMID- 23118492
TI  - High-mobility group box-1 and endothelial cell angiogenic markers in the vitreous
      from patients with proliferative diabetic retinopathy.
AB  - The aim of this study was to measure the levels of high-mobility group box-1
      (HMGB1) in the vitreous fluid from patients with proliferative diabetic
      retinopathy (PDR) and to correlate its levels with clinical disease activity and
      the levels of vascular endothelial growth factor (VEGF), the angiogenic cytokine
      granulocyte-colony-stimulating factor (G-CSF), the endothelial cell angiogenic
      markers soluble vascular endothelial-cadherin (sVE-cadherin), and soluble
      endoglin (sEng). Vitreous samples from 36 PDR and 21 nondiabetic patients were
      studied by enzyme-linked immunosorbent assay. HMGB1, VEGF, sVE-cadherin, and sEng
      levels were significantly higher in PDR patients than in nondiabetics (P = 0.008;
      <0.001; <0.001; 0.003, resp.). G-CSF was detected in only 3 PDR samples. In the
      whole study group, there was significant positive correlation between the levels
      of HMGB1, and sVE-cadherin (r = 0.378, P = 0.007). In PDR patients, there was
      significant negative correlation between the levels of sVE-cadherin and sEng (r =
      -0.517, P = 0.0005). Exploratory regression analysis identified significant
      associations between active PDR and high levels of VEGF (odds ratio = 76.4; 95%
      confidence interval = 6.32-923) and high levels of sEng (odds ratio = 6.01; 95%
      confidence interval = 1.25-29.0). Our findings suggest that HMGB1, VEGF, sVE
      cadherin and sEng regulate the angiogenesis in PDR.

PMID- 23118494
TI  - Epidemiologic features of Vulvovaginal Candidiasis among reproductive-age women
      in India.
AB  - BACKGROUND: Vulvovaginal candidiasis is characterized by curd-like vaginal
      discharge and itching, and is associated with considerable health and economic
      costs. MATERIALS AND METHODS: We examined the incidence, prevalence, and risk
      factors for vulvovaginal candidiasis among a cohort of 898 women in south India.
      Participants completed three study visits over six months, comprised of a
      structured interview and a pelvic examination. RESULTS: The positive predictive
      values for diagnosis of vulvovaginal candidiasis using individual signs or
      symptoms were low (<19%). We did not find strong evidence for associations
      between sociodemographic characteristics and the prevalence of vulvovaginal
      candidiasis. Women clinically diagnosed with bacterial vaginosis had a higher
      prevalence of vulvovaginal candidiasis (Prevalence 12%, 95% CI 8.2, 15.8)
      compared to women assessed to be negative for bacterial vaginosis (Prevalence
      6.5%, 95% 5.3, 7.6); however, differences in the prevalence of vulvovaginal
      candidiasis were not observed by the presence or absence of laboratory-confirmed
      bacterial vaginosis. CONCLUSIONS: For correct diagnosis of vulvovaginal
      candidiasis, laboratory confirmation of infection with Candida is necessary as
      well as assessment of whether the discharge has been caused by bacterial
      vaginosis. Studies are needed of women infected with Candida yeast species to
      determine the risk factors for yeast's overgrowth.

PMID- 23118495
TI  - So many plasminogen receptors: why?
AB  - Plasminogen and plasmin tether to cell surfaces through ubiquitously expressed
      and structurally quite dissimilar family of proteins, as well as some
      nonproteins, that are collectively referred to as plasminogen receptors. Of the
      more than one dozen plasminogen receptors that have been identified, many have
      been shown to facilitate plasminogen activation to plasmin and to protect bound
      plasmin from inactivation by inhibitors. The generation of such localized and
      sustained protease activity is utilized to facilitate numerous cellular
      responses, including responses that depend on cellular migration. However, many
      cells express multiple plasminogen receptors and numerous plasminogen receptors
      are expressed on many different cell types. Furthermore, several different
      plasminogen receptors can be used to support the same cellular response, such as
      inflammatory cell migration. Here, we discuss the perplexing issue: why are there
      so many different Plg-Rs?

PMID- 23118497
TI  - The serine protease plasmin triggers expression of the CC-chemokine ligand 20 in
      dendritic cells via Akt/NF-kappaB-dependent pathways.
AB  - The number of dendritic cells is increased in advanced atherosclerotic lesions.
      In addition, plasmin, which might stimulate dendritic cells, is generated in
      atherosclerotic lesions. Here, we investigated cytokine and chemokine induction
      by plasmin in human dendritic cells. In human atherosclerotic vessel sections,
      plasmin colocalized with dendritic cells and the CC-chemokine ligand 20 (CCL20,
      MIP-3alpha), which is important for homing of lymphocytes and dendritic cells to
      sites of inflammation. Stimulation of human dendritic cells with plasmin, but not
      with catalytically inactivated plasmin, induced transcriptional regulation of
      CCL20. By contrast, proinflammatory cytokines such as TNF-alpha, IL-1alpha, and
      IL-1beta were not induced. The plasmin-mediated CCL20 expression was preceded by
      activation of Akt and MAP kinases followed by activation of the transcription
      factor NF-kappaB as shown by phosphorylation of its inhibitor IkappaBalpha, by
      nuclear localization of p65, its phosphorylation, and binding to NF-kappaB
      consensus sequences. The plasmin-induced CCL20 expression was dependent on Akt-
      and ERK1/2-mediated phosphorylation of IkappaBalpha on Ser32/36 and of p65 on
      Ser276, whereas p38 MAPK appeared to be dispensable. Thus, plasmin triggers
      release of the chemokine CCL20 from dendritic cells, which might facilitate
      accumulation of CCR6(+) immune cells in areas of plasmin generation such as
      inflamed tissues including atherosclerotic lesions.

PMID- 23118498
TI  - Production of ethanol from sugars and lignocellulosic biomass by
      Thermoanaerobacter J1 isolated from a hot spring in Iceland.
AB  - Thermophilic bacteria have gained increased attention as candidates for
      bioethanol production from lignocellulosic biomass. This study investigated
      ethanol production by Thermoanaerobacter strain J1 from hydrolysates made from
      lignocellulosic biomass in batch cultures. The effect of increased initial
      glucose concentration and the partial pressure of hydrogen on end product
      formation were examined. The strain showed a broad substrate spectrum, and high
      ethanol yields were observed on glucose (1.70 mol/mol) and xylose (1.25 mol/mol).
      Ethanol yields were, however, dramatically lowered by adding thiosulfate or by
      cocultivating strain J1 with a hydrogenotrophic methanogen with acetate becoming
      the major end product. Ethanol production from 4.5 g/L of lignocellulosic biomass
      hydrolysates (grass, hemp stem, wheat straw, newspaper, and cellulose) pretreated
      with acid or alkali and the enzymes Celluclast and Novozymes 188 was
      investigated. The highest ethanol yields were obtained on cellulose (7.5 mM.g(
      1)) but the lowest on straw (0.8 mM.g(-1)). Chemical pretreatment increased
      ethanol yields substantially from lignocellulosic biomass but not from cellulose.
      The largest increase was on straw hydrolysates where ethanol production increased
      from 0.8 mM.g(-1) to 3.3 mM.g(-1) using alkali-pretreated biomass. The highest
      ethanol yields on lignocellulosic hydrolysates were observed with hemp
      hydrolysates pretreated with acid, 4.2 mM.g(-1).

PMID- 23118496
TI  - alpha-Enolase, a multifunctional protein: its role on pathophysiological
      situations.
AB  - alpha-Enolase is a key glycolytic enzyme in the cytoplasm of prokaryotic and
      eukaryotic cells and is considered a multifunctional protein. alpha-enolase is
      expressed on the surface of several cell types, where it acts as a plasminogen
      receptor, concentrating proteolytic plasmin activity on the cell surface. In
      addition to glycolytic enzyme and plasminogen receptor functions, alpha-Enolase
      appears to have other cellular functions and subcellular localizations that are
      distinct from its well-established function in glycolysis. Furthermore,
      differential expression of alpha-enolase has been related to several pathologies,
      such as cancer, Alzheimer's disease, and rheumatoid arthritis, among others. We
      have identified alpha-enolase as a plasminogen receptor in several cell types. In
      particular, we have analyzed its role in myogenesis, as an example of
      extracellular remodelling process. We have shown that alpha-enolase is expressed
      on the cell surface of differentiating myocytes, and that inhibitors of alpha
      enolase/plasminogen binding block myogenic fusion in vitro and skeletal muscle
      regeneration in mice. alpha-Enolase could be considered as a marker of
      pathological stress in a high number of diseases, performing several of its
      multiple functions, mainly as plasminogen receptor. This paper is focused on the
      multiple roles of the alpha-enolase/plasminogen axis, related to several
      pathologies.

PMID- 23118499
TI  - Lovastatin production by Aspergillus terreus using agro-biomass as substrate in
      solid state fermentation.
AB  - Ability of two strains of Aspergillus terreus (ATCC 74135 and ATCC 20542) for
      production of lovastatin in solid state fermentation (SSF) using rice straw (RS)
      and oil palm frond (OPF) was investigated. Results showed that RS is a better
      substrate for production of lovastatin in SSF. Maximum production of lovastatin
      has been obtained using A. terreus ATCC 74135 and RS as substrate without
      additional nitrogen source (157.07 mg/kg dry matter (DM)). Although additional
      nitrogen source has no benefit effect on enhancing the lovastatin production
      using RS substrate, it improved the lovastatin production using OPF with maximum
      production of 70.17 and 63.76 mg/kg DM for A. terreus ATCC 20542 and A. terreus
      ATCC 74135, respectively (soybean meal as nitrogen source). Incubation
      temperature, moisture content, and particle size had shown significant effect on
      lovastatin production (P < 0.01) and inoculums size and pH had no significant
      effect on lovastatin production (P > 0.05). Results also have shown that pH 6, 25
      degrees C incubation temperature, 1.4 to 2 mm particle size, 50% initial moisture
      content, and 8 days fermentation time are the best conditions for lovastatin
      production in SSF. Maximum production of lovastatin using optimized condition was
      175.85 and 260.85 mg/kg DM for A. terreus ATCC 20542 and ATCC 74135,
      respectively, using RS as substrate.

PMID- 23118500
TI  - Accelerated fibrinolysis and its propagation on vascular endothelial cells by
      secreted and retained tPA.
AB  - We successfully visualized the secretory dynamics of tissue-type plasminogen
      activator (tPA) tagged by green fluorescent protein (tPA-GFP) from cultured
      vascular endothelial cells (VECs) using total internal reflection fluorescence
      (TIRF) microscopy and demonstrated that tPA-GFP secreted from VECs was retained
      on cell surfaces in a heavy-chain-dependent manner. Progressive binding of
      Alexa568-labeled Glu-plasminogen was also observed on the surface of active tPA
      GFP expressing cells via lysine binding sites (LBS), which was not observed on
      inactive mutant tPA-GFP expressing cells. These results suggest that retained tPA
      on VECs effectively activated plasminogen to plasmin, which then facilitated the
      binding of additional plasminogen on the cell surface by proteolytically cleaving
      surface-associated proteins and exposing their C-terminal lysine residues. Thus
      prolonged retention of tPA appeared to play an important role in initiating and
      amplifying plasmin generation on VECs. LBS-dependent binding of plasminogen was
      also observed as a narrow band at the lytic front of the fibrin mesh formed on
      active tPA-GFP expressing cells, which expanded outward as the lytic area
      increased. This binding was not observed on inactive mutant tPA-GFP expressing
      cells or in the presence of aprotinin. The binding of plasminogen to partially
      digested fibrin appears to be indispensable for spontaneous fibrinolysis.

PMID- 23118501
TI  - CD73 is critical for the resolution of murine colonic inflammation.
AB  - CD73 is a glycosyl-phosphatidylinositol-(GPI-) linked membrane protein that
      catalyzes the extracellular dephosphorylation of adenosine monophosphate (AMP) to
      adenosine. Adenosine is a negative regulator of inflammation and prevents
      excessive cellular damage. We investigated the role of extracellular adenosine in
      the intestinal mucosa during the development of Dextran-Sulfate-Sodium-(DSS-)salt
      induced colitis in mice that lack CD73 (CD73(-/-)) and are unable to synthesize
      extracellular adenosine. We have found that, compared to wild-type (WT) mice,
      CD73(-/-) mice are highly susceptible to DSS-induced colitis. CD73(-/-) mice
      exhibit pronounced weight loss, slower weight recovery, an increase in gut
      permeability, a decrease in expression of tight junctional adhesion molecules, as
      well as unresolved inflammation following the removal of DSS. Moreover, colonic
      epithelia in CD73(-/-) mice exhibited increased TLR9 expression, high levels of
      IL-1beta and TNF-alpha, and constitutive activation of NF-kappaB. We conclude
      that CD73 expression in the colon is critical for regulating the magnitude and
      the resolution of colonic immune responses.

PMID- 23118503
TI  - Enzymatic saccharification and ethanol fermentation of reed pretreated with
      liquid hot water.
AB  - Reed is a widespread-growing, inexpensive, and readily available lignocellulosic
      material source in northeast China. The objective of this study is to evaluate
      the liquid hot water (LHW) pretreatment efficiency of reed based on the enzymatic
      digestibility and ethanol fermentability of water-insoluble solids (WISs) from
      reed after the LHW pretreatment. Several variables in the LHW pretreatment and
      enzymatic hydrolysis process were optimized. The conversion of glucan to glucose
      and glucose concentrations are considered as response variables in different
      conditions. The optimum conditions for the LHW pretreatment of reed area
      temperature of 180 degrees C for 20min and a solid-to-liquid ratio of 1 : 10.
      These optimum conditions for the LHW pretreatment of reed resulted in a cellulose
      conversion rate of 82.59% in the subsequent enzymatic hydrolysis at 50 degrees C
      for 72 h with a cellulase loading of 30 filter paper unit per gram of oven-dried
      WIS. Increasing the pretreatment temperature resulted in a higher enzymatic
      digestibility of the WIS from reed. Separate hydrolysis and fermentation of WIS
      showed that the conversion of glucan to ethanol reached 99.5% of the theoretical
      yield. The LHW pretreatment of reed is a suitable method to acquire a high
      recovery of fermentable sugars and high ethanol conversion yield.

PMID- 23118502
TI  - Bacterial plasminogen receptors: mediators of a multifaceted relationship.
AB  - Multiple species of bacteria are able to sequester the host zymogen plasminogen
      to the cell surface. Once localised to the bacterial surface, plasminogen can act
      as a cofactor in adhesion, or, following activation to plasmin, provide a source
      of potent proteolytic activity. Numerous bacterial plasminogen receptors have
      been identified, and the mechanisms by which they interact with plasminogen are
      diverse. Here we provide an overview of bacterial plasminogen receptors and
      discuss the diverse role bacterial plasminogen acquisition plays in the
      relationship between bacteria and the host.

PMID- 23118504
TI  - The CD39-adenosinergic axis in the pathogenesis of immune and nonimmune diabetes.
AB  - Diabetes mellitus encompasses two distinct disease processes: autoimmune Type 1
      (T1D) and nonimmune Type 2 (T2D) diabetes. Despite the disparate aetiologies, the
      disease phenotype of hyperglycemia and the associated complications are similar.
      In this paper, we discuss the role of the CD39-adenosinergic axis in the
      pathogenesis of both T1D and T2D, with particular emphasis on the role of CD39
      and CD73.

PMID- 23118505
TI  - Changes in the material characteristics of maize straw during the pretreatment
      process of methanation.
AB  - Pretreatment technology is important to the direct methanation of straw. This
      study used fresh water, four bacterium agents (stem rot agent, "result" microbe
      decomposition agent, straw pretreatment composite bacterium agent, and complex
      microorganism agent), biogas slurry, and two chemical reagents (sodium hydroxide
      and urea) as pretreatment promoters. Different treatments were performed, and the
      changes in the straw pH value, temperature, total solid (TS), volatile solid
      (VS), and carbon-nitrogen ratio (C/N ratio) under different pretreatment
      conditions were analyzed. The results showed that chemical promoters were more
      efficient than biological promoters in straw maturity. Pretreatment using sodium
      hydroxide induced the highest degree of straw maturity. However, its C/N ratio
      had to be reduced during fermentation. In contrast, the C/N ratio of the urea
      pretreated straw was low and was easy to regulate when used as anaerobic
      digestion material. The biogas slurry pretreatment was followed by pretreatments
      using four different bacterium agents, among which the effect of the complex
      microorganism agent (BA4) was more efficient than the others. The current study
      is significant to the direct and efficient methanation of straw.

PMID- 23118507
TI  - The role of nephritis-associated plasmin receptor (NAPlr) in glomerulonephritis
      associated with streptococcal infection.
AB  - It is well known that glomerulonephritis can occur after streptococcal infection,
      which is classically referred to as acute poststreptococcal glomerulonephritis
      (APSGN). The pathogenic mechanism of APSGN has been described by so-called immune
      complex theory, which involves glomerular deposition of nephritogenic
      streptococcal antigen and subsequent formation of immune complexes in situ and/or
      the deposition of circulating antigen-antibody complexes. However, the exact
      entity of the causative antigen has remained a matter of debate. We isolated a
      nephritogenic antigen for APSGN from the cytoplasmic fractions of group A
      streptococcus (GAS) depending on the affinity for IgG of APSGN patients. The
      amino acid and the nucleotide sequences of the isolated protein revealed to be
      highly identical to those of reported plasmin(ogen) receptor of GAS. Thus, we
      termed this antigen nephritis-associated plasmin receptor (NAPlr).
      Immunofluorescence staining of the renal biopsy tissues with anti-NAPlr antibody
      revealed glomerular NAPlr deposition in essentially all patients with early-phase
      APSGN. Furthermore, glomerular plasmin activity was detected by in situ
      zymography in the distribution almost identical to NAPlr deposition in renal
      biopsy tissues of APSGN patients. These data suggest that NAPlr has a direct,
      nonimmunologic function as a plasmin receptor and may contribute to the
      pathogenesis of APSGN by maintaining plasmin activity.

PMID- 23118506
TI  - The biochemistry and regulation of S100A10: a multifunctional plasminogen
      receptor involved in oncogenesis.
AB  - The plasminogen receptors mediate the production and localization to the cell
      surface of the broad spectrum proteinase, plasmin. S100A10 is a key regulator of
      cellular plasmin production and may account for as much as 50% of cellular
      plasmin generation. In parallel to plasminogen, the plasminogen-binding site on
      S100A10 is highly conserved from mammals to fish. S100A10 is constitutively
      expressed in many cells and is also induced by many diverse factors and
      physiological stimuli including dexamethasone, epidermal growth factor,
      transforming growth factor-alpha, interferon-gamma, nerve growth factor,
      keratinocyte growth factor, retinoic acid, and thrombin. Therefore, S100A10 is
      utilized by cells to regulate plasmin proteolytic activity in response to a wide
      diversity of physiological stimuli. The expression of the oncogenes, PML-RARalpha
      and KRas, also stimulates the levels of S100A10, suggesting a role for S100A10 in
      pathophysiological processes such as in the oncogenic-mediated increases in
      plasmin production. The S100A10-null mouse model system has established the
      critical role that S100A10 plays as a regulator of fibrinolysis and oncogenesis.
      S100A10 plays two major roles in oncogenesis, first as a regulator of cancer cell
      invasion and metastasis and secondly as a regulator of the recruitment of tumor
      associated cells, such as macrophages, to the tumor site.

PMID- 23118508
TI  - The plasminogen system in regulating stem cell mobilization.
AB  - The treatment of patients with hematopoietic progenitor and stem cells (HPSCs) to
      reconstitute hematopoiesis after myeloablative therapy or to repair ischemia
      after myocardial infarction has significantly improved clinical outcomes.
      Successful blood or bone marrow transplants require a sufficient number of HPSCs
      capable of homing to the injured site to regenerate tissue. Granulocyte-colony
      stimulating factor (G-CSF) is widely used clinically for stem cell mobilization.
      However, in some patients the response is poor, thus a better understanding of
      the mechanisms underlying G-CSF-regulated stem cell mobilization is needed. The
      pasminogen (Plg) system is the primary fibrinolytic pathway responsible for clot
      dissolution after thrombosis. Recent evidence suggests that Plg plays a pivotal
      role in stem cell mobilization from the bone marrow to the peripheral
      circulation, particularly in HPSC mobilization in response to G-CSF. This paper
      will discuss the potential mechanisms by which the Plg system regulates stem cell
      mobilization, focusing on stepwise proteolysis and signal transduction during
      HPSC egress from their bone marrow niche. Clear elucidation of the underlying
      mechanisms may lead to the development of new Plg-based therapeutic strategies to
      improve stem cell mobilization in treating hematological and cardiovascular
      diseases.

PMID- 23118510
TI  - Signal-BNF: a Bayesian network fusing approach to predict signal peptides.
AB  - A signal peptide is a short peptide chain that directs the transport of a protein
      and has become the crucial vehicle in finding new drugs or reprogramming cells
      for gene therapy. As the avalanche of new protein sequences generated in the
      postgenomic era, the challenge of identifying new signal sequences has become
      even more urgent and critical in biomedical engineering. In this paper, we
      propose a novel predictor called Signal-BNF to predict the N-terminal signal
      peptide as well as its cleavage site based on Bayesian reasoning network. Signal
      BNF is formed by fusing the results of different Bayesian classifiers which used
      different feature datasets as its input through weighted voting system.
      Experiment results show that Signal-BNF is superior to the popular online
      predictors such as Signal-3L and PrediSi. Signal-BNF is featured by high
      prediction accuracy that may serve as a useful tool for further investigating
      many unclear details regarding the molecular mechanism of the zip code protein
      sorting system in cells.

PMID- 23118512
TI  - PHA productivity and yield of Ralstonia eutropha when intermittently or
      continuously fed a mixture of short chain fatty acids.
AB  - The research described in this present study was part of a larger effort focused
      on developing a dual substrate, dual fermentation process to produce
      Polyhydroxyalkanoate (PHA). The focus of this study was developing and optimizing
      a strategy for feeding a mixture of SCFAs (simulated ARF) and maximizing PHA
      production in a cost-effective way. Three different feeding strategies were
      examined in this study. The substrate evaluated in this study for the growth
      phase of R. eutropha was condensed corn solubles, a low-value byproduct of the
      dry-mill, corn ethanol industry. The culture was grown to high cell densities in
      nitrogen-supplemented condensed corn solubles media in 5 L bioreactors. The
      overall growth rate of R. eutropha was 0.2 h(-1). The 20 mL ARF feeding every 3 h
      from 48 to 109 h strategy gave the best results in terms of PHA production. PHA
      productivity (0.0697 g L(-1) h(-1)), PHA concentration (8.37 g L(-1)), and PHA
      content (39.52%) were the highest when ARF was fed every 3 h for 61 h. This study
      proved that condensed corn solubles can be potentially used as a growth medium to
      boost PHA production by R. eutropha thus reducing the overall cost of biopolymer
      production.

PMID- 23118511
TI  - Long-term left ventricular remodelling in rat model of nonreperfused myocardial
      infarction: sequential MR imaging using a 3T clinical scanner.
AB  - Purpose. To evaluate whether 3T clinical MRI with a small-animal coil and
      gradient-echo (GE) sequence could be used to characterize long-term left
      ventricular remodelling (LVR) following nonreperfused myocardial infarction (MI)
      using semi-automatic segmentation software (SASS) in a rat model. Materials and
      Methods. 5 healthy rats were used to validate left ventricular mass (LVM)
      measured by MRI with postmortem values. 5 sham and 7 infarcted rats were scanned
      at 2 and 4 weeks after surgery to allow for functional and structural analysis of
      the heart. Measurements included ejection fraction (EF), end-diastolic volume
      (EDV), end-systolic volume (ESV), and LVM. Changes in different regions of the
      heart were quantified using wall thickness analyses. Results. LVM validation in
      healthy rats demonstrated high correlation between MR and postmortem values.
      Functional assessment at 4 weeks after MI revealed considerable reduction in EF,
      increases in ESV, EDV, and LVM, and contractile dysfunction in infarcted and
      noninfarcted regions. Conclusion. Clinical 3T MRI with a small animal coil and GE
      sequence generated images in a rat heart with adequate signal-to-noise ratio
      (SNR) for successful semiautomatic segmentation to accurately and rapidly
      evaluate long-term LVR after MI.

PMID- 23118513
TI  - A novel partially biobased PAN-lignin blend as a potential carbon fiber
      precursor.
AB  - Blends of polyacrylonitrile (PAN) and lignin were prepared with three different
      lignin types by solution blending and solution casting. Among three types of
      lignin, one type was chosen and different blend concentrations were prepared and
      casted. The casted blend films were characterized chemically with fourier
      transform infrared spectroscopy (FTIR), and thermally with thermogravimetric
      analysis (TGA). The mechanical properties of the blends were measured using
      dynamic mechanical analysis (DMA). FTIR analysis shows an excellent interaction
      of PAN and lignin. The interaction of the lignins and PAN was confirmed by TGA
      analysis. The DMA results reveal that the lignin enhance the mechanical
      properties of PAN at room temperature and elevated temperatures. The blend
      structure and morphology were observed using scanning electron microscopy (SEM).
      SEM images show that excellent polymer blends were prepared. The results show
      that it is possible to develop a new precursor material with a blend of lignin
      and PAN. These studies show that the side product of paper and cellulosic
      bioethanol industries, namely, lignin can be used for new application areas.

PMID- 23118509
TI  - Bacterial plasminogen receptors utilize host plasminogen system for effective
      invasion and dissemination.
AB  - In order for invasive pathogens to migrate beyond the site of infection, host
      physiological barriers such as the extracellular matrix, the basement membrane,
      and encapsulating fibrin network must be degraded. To circumvent these
      impediments, proteolytic enzymes facilitate the dissemination of the
      microorganism. Recruitment of host proteases to the bacterial surface represents
      a particularly effective mechanism for enhancing invasiveness. Plasmin is a broad
      spectrum serine protease that degrades fibrin, extracellular matrices, and
      connective tissue. A large number of pathogens express plasminogen receptors
      which immobilize plasmin(ogen) on the bacterial surface. Surface-bound
      plasminogen is then activated by plasminogen activators to plasmin through
      limited proteolysis thus triggering the development of a proteolytic surface on
      the bacteria and eventually assisting the spread of bacteria. The host hemostatic
      system plays an important role in systemic infection. The interplay between
      hemostatic processes such as coagulation and fibrinolysis and the inflammatory
      response constitutes essential components of host defense and bacterial invasion.
      The goal of this paper is to highlight mechanisms whereby pathogenic bacteria, by
      engaging surface receptors, utilize and exploit the host plasminogen and
      fibrinolytic system for the successful dissemination within the host.

PMID- 23118514
TI  - miRNA589 regulates epithelial-mesenchymal transition in human peritoneal
      mesothelial cells.
AB  - Background. microRNA (miRNA, miR) are thought to interact with multiple mRNAs
      which are involved in the EMT process. But the role of miRNAs in peritoneal
      fibrosis has remained unknown. Objective. To determine if miRNA589 regulates the
      EMT induced by TGFbeta1 in human peritoneal mesothelial cell line (HMrSV5 cells).
      Methods. 1. Level of miR589 was detected in both human peritoneal mesothelial
      cells (HPMCs) isolated from continuous ambulatory peritoneal dialysis (CAPD)
      patients' effluent and HMrSV5 cells treated with or without TGFbeta1. 2. HMrSV5
      cells were divided into three groups: control group, TGFbeta1 group, and pre-miR
      589+TGFbeta1 group. The level of miRNA589 was determined by realtime PCR. The
      expressions of ZO-1, vimentin, and E-cadherin in HPMCs were detected,
      respectively. Results. Decreased level of miRNA589 was obtained in either HPMCs
      of long-term CAPD patients or HMrSV5 cells treated with TGFbeta1. In vitro,
      TGFbeta1 led to upregulation of vimentin and downregulation of ZO-1 as well as E
      cadherin in HMrSV5 cells, which suggested EMT, was induced. The changes were
      accompanied with notably decreased level of miRNA589 in HMrSV5 cells treated with
      TGFbeta1. Overexpression of miRNA589 by transfection with pre-miRNA589 partially
      reversed these EMT changes. Conclusion. miRNA589 mediates TGFbeta1 induced EMT in
      human peritoneal mesothelial cells.

PMID- 23118515
TI  - Analysis of casein biopolymers adsorption to lignocellulosic biomass as a
      potential cellulase stabilizer.
AB  - Although lignocellulosic materials have a good potential to substitute current
      feedstocks used for ethanol production, conversion of these materials to
      fermentable sugars is still not economical through enzymatic hydrolysis. High
      cost of cellulase has prompted research to explore techniques that can prevent
      from enzyme deactivation. Colloidal proteins of casein can form monolayers on
      hydrophobic surfaces that alleviate the de-activation of protein of interest.
      Scanning electron microscope (SEM), fourier transform infrared spectroscopy (FT
      IR), capillary electrophoresis (CE), and Kjeldahl and BSA protein assays were
      used to investigate the unknown mechanism of action of induced cellulase activity
      during hydrolysis of casein-treated biomass. Adsorption of casein to biomass was
      observed with all of the analytical techniques used and varied depending on the
      pretreatment techniques of biomass. FT-IR analysis of amides I and II suggested
      that the substructure of protein from casein or skim milk were deformed at the
      time of contact with biomass. With no additive, the majority of one of the
      cellulase mono-component, 97.1 +/- 1.1, was adsorbed to CS within 24 h, this
      adsorption was irreversible and increased by 2% after 72 h. However, biomass
      treatment with skim-milk and casein reduced the adsorption to 32.9% +/- 6.0 and
      82.8% +/- 6.0, respectively.

PMID- 23118516
TI  - Plasminogen binding proteins and plasmin generation on the surface of Leptospira
      spp.: the contribution to the bacteria-host interactions.
AB  - Leptospirosis is considered a neglected infectious disease of human and
      veterinary concern. Although extensive investigations on host-pathogen
      interactions have been pursued by several research groups, mechanisms of
      infection, invasion and persistence of pathogenic Leptospira spp. remain to be
      elucidated. We have reported the ability of leptospires to bind human plasminogen
      (PLG) and to generate enzimatically active plasmin (PLA) on the bacteria surface.
      PLA-coated Leptospira can degrade immobilized ECM molecules, an activity with
      implications in host tissue penetration. Moreover, we have identified and
      characterized several proteins that may act as PLG-binding receptors, each of
      them competent to generate active plasmin. The PLA activity associated to the
      outer surface of Leptospira could hamper the host immune attack by conferring the
      bacteria some benefit during infection. The PLA-coated leptospires obstruct
      complement C3b and IgG depositions on the bacterial surface, most probably
      through degradation. The decrease of leptospiral opsonization might be an
      important aspect of the immune evasion strategy. We believe that the presence of
      PLA on the leptospiral surface may (i) facilitate host tissue penetration, (ii)
      help the bacteria to evade the immune system and, as a consequence, (iii) permit
      Leptospira to reach secondary sites of infection.

PMID- 23118518
TI  - Characterization of plasminogen binding to NB4 promyelocytic cells using
      monoclonal antibodies against receptor-induced binding sites in cell-bound
      plasminogen.
AB  - The NB4 promyelocytic cell line exhibits many of the characteristics of acute
      promyelocytic leukemia blast cells, including the translocation (15 : 17) that
      fuses the PML gene on chromosome 15 to the RARalpha gene on chromosome 17. These
      cells have a very high fibrinolytic capacity. In addition to a high secretion of
      urokinase, NB4 cells exhibit a 10-fold higher plasminogen binding capacity
      compared with other leukemic cell lines. When tissue-type plasminogen activator
      was added to acid-treated cells, plasmin generation was 20-26-fold higher than
      that generated by U937 cells or peripheral blood neutrophils, respectively. We
      found that plasminogen bound to these cells can be detected by fluorescence
      activated cell sorting using an antiplasminogen monoclonal antibody that
      specifically reacts with this antigen when it is bound to cell surfaces. All
      trans retinoid acid treatment of NB4 cells markedly decreased the binding of this
      monoclonal antibody. This cell line constitutes a unique model to explore
      plasminogen binding and activation on cell surfaces that can be modulated by all
      trans retinoid acid treatment.

PMID- 23118517
TI  - Ectonucleotidases in tumor cells and tumor-associated immune cells: an overview.
AB  - Increasing evidence points out that genetic alteration does not guarantee the
      development of a tumor and indicates that complex interactions of tumor cells
      with the microenvironment are fundamental to tumorigenesis. Among the
      pathological alterations that give tumor cells invasive potential, disruption of
      inflammatory response and the purinergic signaling are emerging as an important
      component of cancer progression. Nucleotide/nucleoside receptor-mediated cell
      communication is orchestrated by ectonucleotidases, which efficiently hydrolyze
      ATP, ADP, and AMP to adenosine. ATP can act as danger signaling whereas
      adenosine, acts as a negative feedback mechanism to limit inflammation. Many
      tumors exhibit alterations in ATP-metabolizing enzymes, which may contribute to
      the pathological events observed in solid cancer. In this paper, the main changes
      occurring in the expression and activity of ectonucleotidases in tumor cells as
      well as in tumor-associated immune cells are discussed. Furthermore, we focus on
      the understanding of the purinergic signaling primarily as exemplified by
      research done by the group on gliomas.

PMID- 23118519
TI  - How to promote and preserve eyelid health.
AB  - Disorders of the lacrimal functional unit are common in ophthalmological
      practice, with meibomian gland dysfunction, blepharitis, and dry eye forming a
      significant part of the general ophthalmologist's practice. The eyelid and its
      associated structures form a complex organ designed to protect the fragile
      corneal surface and improve visual acuity. This organ is subject to a number of
      disorders, including meibomian gland dysfunction, dry eye syndrome, anterior
      blepharitis, allergic and dermatological conditions, and disorders associated
      with contact lens use. Although commonly described separately, disorders of the
      lacrimal function unit are better considered as a group of interacting
      pathologies that have inflammatory mediators as a central feature. Eyelid
      hygiene, in the sense of routine cleansing and massage of the eyelids, is well
      accepted in the management of many disorders of the eyelid. However, a broader
      concept of eyelid health may be appropriate, in which eyelid cleansing is but a
      part of a more complete program of care that includes screening and risk
      assessment, patient education, and coaching. The ophthalmologist has an important
      role to play in helping patients persist with routine eyelid care that may be
      long-term or lifelong. A number of preparations exist to make routine eyelid care
      both more effective and more pleasant, and might also improve compliance. Several
      such preparations have been devised, and are being assessed in clinical studies,
      and appear to be effective and preferred by patients over traditional soap and
      water or baby shampoo.

PMID- 23118520
TI  - Current primary open-angle glaucoma treatments and future directions.
AB  - Primary open-angle glaucoma (POAG) is a leading cause of blindness with no known
      cure. Management of the disease focuses on lowering intraocular pressure (IOP)
      with current classes of drugs like prostaglandin analogs, beta-blockers, alpha
      agonists, and carbonic anhydrase inhibitors. These treatments have not helped all
      patients. Some patients continue to experience deterioration in the optic nerve
      even though their IOPs are within the normal range. New views have surfaced about
      other pathophysiological processes (such as oxidative stress, vascular
      dysfunction, and retinal cell apoptosis) being involved in POAG progression, and
      adjunctive treatments with drugs like memantine, bis(7)-tacrine, nimodipine, and
      mirtogenol are advocated. This review examines the current and proposed
      treatments for POAG. Some of the proposed drugs (bis(7)-tacrine, nimodipine,
      vitamin E, and others) have shown good promise, mostly as monotherapy in various
      clinical trials. It is recommended that both the current and proposed drugs be
      put through further robust trials in concurrent administration and evaluated.

PMID- 23118521
TI  - Improvement in ocular cicatricial pemphigoid following treatment for porphyria
      cutanea tarda.
AB  - A 64-year-old Caucasian male complaining of redness and tearing for 3 years in
      both eyes was referred for evaluation of cicatricial conjunctivitis. Ocular
      cicatricial pemphigoid was suspected and this diagnosis was confirmed through
      biopsy. The patient's condition showed moderate improvement following treatment
      with methotrexate and mycophenolate mofetil. The patient was later diagnosed with
      porphyria cutanea tarda and phlebotomy treatments were subsequently initiated.
      The patient's ocular symptoms improved further after he began receiving these
      phlebotomy treatments, and conventional treatment was discontinued. The authors
      hypothesize that circulating porphyrins activated by ultraviolet light could be
      the cause of the ocular cicatricial pemphigoid in this patient.

PMID- 23118522
TI  - Superior segmental optic nerve hypoplasia accompanied by progressive normal
      tension glaucoma.
AB  - This is the first case report of a superior segmental optic hypoplasia (SSOH)
      combined with normal-tension glaucoma accompanied by a progressive glaucomatous
      visual field defect. A 40-year-old man, incidentally diagnosed as having
      bilateral SSOH, had disc hemorrhage associated with expansion of the width of a
      retinal nerve fiber layer defect and deterioration of a visual field defect in
      the right eye during the follow-up period. His left eye showed a stable visual
      field. The diurnal variation in intraocular pressure (IOP) showed a higher mean
      IOP in his right eye compared with his left eye, although both IOPs remained
      under 21 mmHg.

PMID- 23118524
TI  - Anesthetic keratopathy presenting as bilateral Mooren-like ulcers.
AB  - This observational case report describes the development of bilateral Mooren-like
      ulcers in a patient with anesthetic keratopathy. A 42-year-old man with a recent
      history of minor eye trauma and pain self-treated with tetracaine eye drops
      presented with complaints of acutely worsening vision and severe pain
      bilaterally. His visual acuity at presentation was limited to hand motion. Slit
      lamp examination revealed bilateral epithelial defects at the center of the
      cornea, and an area of stromal infiltration and thinning with an undermining
      leading edge resembling a Mooren's ulcer in both eyes. Corneal haze and hypopyon
      were visible. Anesthetic use was halted immediately and the patient was started
      on prednisolone and mycophenolate mofetil (Cellcept((r))), after which visual
      acuity gradually improved and pain decreased. Despite improvement of symptoms,
      residual epithelial defects remained, and the patient was ultimately treated with
      keratoplasty for recovery of vision. We suggest that anesthetic keratopathy
      should be included in the differential diagnosis for any patient presenting with
      ring-shaped stromal infiltrates or nonhealing epithelial defects.

PMID- 23118525
TI  - Treatment of experienced and naive patients with hepatitis C: focus on
      telaprevir.
AB  - Telaprevir (TVR) is an orally available protease inhibitor of the hepatitis C
      virus that in association with pegylated interferon and ribavirin (PR) was shown
      to improve the rates of sustained virological response and potentially reduce
      treatment duration in adult patients with chronic hepatitis C genotype. Despite
      its robust activity in both treatment-naive and experienced patients, the
      addition of TVR to PR is counterbalanced by increased costs and adverse events;
      moreover, there are still areas of uncertainty that regard treatment of patients
      with advanced liver disease, the role of patient stratification by genetic
      predictors, and the use/need for a lead-in phase with PR. Since TVR regimens have
      been associated with the risk of viral mutants that may cause treatment failure
      and jeopardize future therapeutic strategies with direct-acting antiviral agents,
      early stopping rules have been designed to protect patients with a poor
      virological response to TVR regimens against such a risk.

PMID- 23118526
TI  - Clinical use of biologics in vasculitis syndromes.
AB  - Vasculitis syndromes are relative rare conditions but can cause significant
      mortality and morbidity if not treated adequately. Recent advances in
      immunosuppressant therapy have radically changed the course of these diseases.
      However, the standard therapy is not always well tolerated by patients, and some
      cases are refractory to treatment. New therapeutic possibilities have emerged
      with the use of so-called "biologics," a new class of genetically engineered
      drugs used for inflammatory rheumatic diseases, including rheumatoid arthritis,
      ankylosing spondylitis, and psoriatic arthritis. In the present review,
      summarized are the most recent data on the efficacy and safety of biologics in
      the treatment of vasculitis syndromes that cannot be treated with standard
      therapy.

PMID- 23118527
TI  - Therapy effects of gold nanorods on the CNE-1 nasopharyngeal carcinoma cell line.
AB  - The use of nanocarriers to deliver drugs to tumor tissue is one of the most
      important strategies in cancer therapeutics. Recently, gold nanorods (GNRs) have
      begun to be used in cancer therapy because of their unique properties. The
      purpose of this study was to show the potential that GNRs have against human
      nasopharyngeal carcinoma CNE-1 cells, using near-infrared (NIR) laser light.
      Transmission electron microscopic and ultraviolet-visible spectroscopic
      investigations confirmed the efficient uptake of the GNRs by CNE-1 and human
      rhinal epithelia cells. The in vitro NIR photothermal therapy for the CNE-1 and
      rhinal epithelia cells was designed in three groups: (1) control, (2) laser
      alone, and (3) GNRs with laser. Fluorescence microscopy images indicated that, at
      some GNR concentrations and some intensities of NIR laser, GNRs with laser
      therapy could induce cell death for CNE-1 cells while keeping the rhinal
      epithelia cells healthy. Therefore, the results of this study suggest that using
      GNRs with NIR laser therapy can selectively destruct CNE-1 cells while having no
      effect on normal (rhinal epithelia) cells.

PMID- 23118528
TI  - Multicomponent nanoparticles as nonviral vectors for the treatment of Fabry
      disease by gene therapy.
AB  - PURPOSE: Gene-mediated enzyme replacement is a reasonable and highly promising
      approach for the treatment of Fabry disease (FD). The objective of the present
      study was to demonstrate the potential applications of solid lipid nanoparticle
      (SLN)-based nonviral vectors for the treatment of FD. METHODS: SLNs containing
      the pR-M10-alphaGal A plasmid that encodes the alpha-Galactosidase A (alpha-Gal
      A) enzyme were prepared and their in vitro transfection efficacy was studied in
      Hep G2 cells. We also studied the cellular uptake of the vectors and the
      intracellular disposition of the plasmid. RESULTS: The enzymatic activity of the
      cells treated with the vectors increased significantly relative to the untreated
      cells, regardless of the formulation assayed. When the SLNs were prepared with
      protamine or dextran and protamine, the activity of the alpha-Gal A enzyme by the
      transfected Hep G2 cells increased up to 12-fold compared to that of untreated
      cells. CONCLUSION: With this work we have revealed in Hep G2 cells the ability of
      a multicomponent system based on SLNs to act as efficient nonviral vectors to
      potentially correct low alpha-Gal A activity levels in FD with gene therapy.

PMID- 23118529
TI  - Randomized crossover study in patients with neuroendocrine tumors to assess
      patient preference for lanreotide Autogel((r)) given by either self/partner or a
      health care professional.
AB  - BACKGROUND: Lanreotide Autogel((r)) is supplied in prefilled syringes. Therefore,
      it is possible for patients with neuroendocrine tumors to use self-/partner
      administered injections. The primary objective of this study was to assess the
      proportion of patients preferring self/partner injections over injections
      administered by health care professionals, and to describe the impact of
      self/partner administration on efficacy, safety, and costs. METHODS: Of 62
      eligible patients, 26 (42%) patients with neuroendocrine tumors treated with a
      stable dose of lanreotide Autogel 90 mg or 120 mg every 4 weeks agreed to
      participate in this Phase IV, international, open-label, crossover study,
      conducted at hospitals in Sweden, Norway, and Denmark. Patients were randomized
      to two blocks, starting with administration of lanreotide Autogel by either
      self/partner or a health care professional. Preference for injections
      administered by self/partner or health care professionals was measured, as well
      as efficacy, safety, and health care resource utilization (both direct and
      indirect costs). RESULTS: Of 25 evaluable patients, 22 (88%) preferred
      self/partner injections, mainly because they experienced increased independence.
      Based on all patients asked to participate (n = 62), 35% preferred self/partner
      injections on a regular basis. There was no difference in efficacy or safety
      between the two administration blocks. CONCLUSION: Many patients with
      neuroendocrine tumors prefer self/partner injection of lanreotide Autogel, and
      are able to self/partner inject without any impact on efficacy or safety. This
      administration method seems to provide a good alternative for suitable patients
      to increase patient independence and reduce the number of clinic visits.

PMID- 23118530
TI  - The use of capecitabine in daily practice: a study on adherence and patients'
      experiences.
AB  - BACKGROUND: Adherence to pharmacological therapy is a complex and multifactorial
      issue that can substantially alter the outcome of treatment. Especially when
      using long-term medication, cancer patients have adherence rates similar to those
      of patients with other diseases. The consequences of poor adherence are poor
      health outcomes and increased health care costs. Only few studies have focused on
      the use of oral anticancer agents in daily practice. Information about the
      reasons for nonadherence is essential for the development of interventions that
      may improve adherence. This report presents the CAPER-capecitabine protocol,
      which is designed to study the adherence to capecitabine and the influence of
      patient attitudes towards medication and self-reported side effects. Furthermore,
      the relationships between patient characteristics, disease characteristics, side
      effects, quality of life, patient beliefs and attitudes towards disease and
      medication, dose adjustments, reasons for discontinuation, and plasma
      concentration of three of the main metabolites, including the active compound 5
      fluorouracil, will be explored. METHODS: In this multicenter, prospective,
      observational cohort study, 90 patients aged 18 years or older starting treatment
      with capecitabine will be included and followed for a period up to five cycles.
      The main study parameters are adherence, patient attitudes towards medication,
      and the number and grade of patient-reported side effects. At baseline and during
      week 2 of cycles 1, 3 and 5, patients will be asked to donate blood and fill out
      a questionnaire. Blood samples will be analyzed for plasma concentration of the
      metabolites, 5'-deoxy-5-fluorouridine, 5-fluorouracil, and alpha-fluoro-beta
      alanine. The CAPER-capecitabine trial is closely related to the CAPER-erlotinib
      trial. DISCUSSION: The aim of the present study is to get more insight into
      patient experiences with the use of capecitabine in daily practice and the
      various aspects that govern adherence. We hypothesize that patient attitudes
      towards medication and the side effects experienced play an important role in the
      way patients use capecitabine. We expect that our findings will be useful for
      health care professionals in developing interventions to support patients in
      improving adherence and persistence with the use of capecitabine.

PMID- 23118531
TI  - Linking self-determined functional problems of patients with neck pain to the
      International Classification of Functioning, Disability, and Health (ICF).
AB  - OBJECTIVE: To describe commonly reported self-determined functional problems in
      patients with neck pain and to evaluate their fit to the components of the
      International Classification of Functioning, Disability, and Health (ICF).
      METHODS: Overall, 249 patients were included in this cross-sectional study that
      comprised patients with neck pain referred to the outpatient clinic at Oslo
      University Hospital (2007-2009). Patients were asked to report their three most
      significant functional problems on the Patient-Specific Functional Scale, a self
      determined measure of function. The ICF was used as a tool for analysis.
      Meaningful concepts within the functional problems were identified, coded, and
      linked to second-level categories within the components of "body functions," and
      "activities and participation." Two researchers performed coding and linking
      independently. The ICF categories were presented by percentage of the total
      number of functional problems linked to the ICF. RESULTS: Of 628 reported
      functional problems, 13 meaningful ICF domains were identified: four domains
      belonging to the body functions component (b) and nine domains belonging to
      activities and participation components (d). Within the 88 second-level ICF
      classification categories of body functions, the most frequently reported items
      were sleep function (b134; 27%) and mobility of joint functions (b710; 26%).
      Within the 538 second-level categories of activities and participation,
      remunerative employment was reported as the most frequent item (d850; 15%),
      closely followed by doing housework (d640; 14%), and recreation and leisure
      activities (d920; 13%). Only two meaningful concepts, described as "be active"
      and "to function after activities," were not assigned to a specific ICF category.
      CONCLUSION: The majority of the specific functional problems presented by
      patients in this study showed a good fit with the ICF model. The substantial
      number of links to the activities and participation categories, such as mobility,
      domestic life, employment, and social and civic life, suggests that a
      comprehensive approach, as well as the involvement of a multidisciplinary team,
      should be present in the rehabilitation of neck pain-related disability.

PMID- 23118532
TI  - Proposed model of integrated care to improve health outcomes for individuals with
      multimorbidities.
AB  - Multimorbidity is defined as the coexistence of multiple chronic conditions.
      Individuals with multimorbidity typically present with complex needs and show
      significant changes in their functional health and quality of life.
      Multimorbidity in the aging population is well recognized, but there has been
      limited research on ways to manage the problem effectively. More recent studies
      have demonstrated a high prevalence of multimorbidity in the younger demographics
      aged under 65 years. There is a definite need to develop models of care that can
      manage these individuals effectively and mitigate the impact of illness on
      individuals and the financial burden to the health care system. An integrated
      model of care has been developed and implemented in a facility in Nova Scotia
      that routinely treats individuals with multiple chronic conditions. This care
      model is designed to address the specific needs of this complex patient
      population, with integrated and coordinated care modules that meet the needs of
      the person versus the disease. The results of a pilot evaluation of this care
      model are also discussed.

PMID- 23118533
TI  - Extubation process in bed-ridden elderly intensive care patients receiving
      inspiratory muscle training: a randomized clinical trial.
AB  - BACKGROUND: The purpose of this study was to evaluate the extubation process in
      bed-ridden elderly intensive care patients receiving inspiratory muscle training
      (IMT) and identify predictors of successful weaning. METHODS: Twenty-eight
      elderly intubated patients in an intensive care unit were randomly assigned to an
      experimental group (n = 14) that received conventional physiotherapy plus IMT
      with a Threshold IMT((r)) device or to a control group (n = 14) that received
      only conventional physiotherapy. The experimental protocol for muscle training
      consisted of an initial load of 30% maximum inspiratory pressure, which was
      increased by 10% daily. The training was administered for 5 minutes, twice daily,
      7 days a week, with supplemental oxygen from the beginning of weaning until
      extubation. Successful extubation was defined by the ventilation time measurement
      with noninvasive positive pressure. A vacuum manometer was used for measurement
      of maximum inspiratory pressure, and the patients' Tobin index values were
      measured using a ventilometer. RESULTS: The maximum inspiratory pressure
      increased significantly (by 7 cm H(2)O, 95% confidence interval [CI] 4-10), and
      the Tobin index decreased significantly (by 16 breaths/ min/L, 95% CI -26 to 6)
      in the experimental group compared with the control group. The Chi-squared
      distribution did not indicate a significant difference in weaning success between
      the groups (chi(2) = 1.47; P = 0.20). However, a comparison of noninvasive
      positive pressure time dependence indicated a significantly lower value for the
      experimental group (P = 0.0001; 95% CI 13.08-18.06). The receiver-operating
      characteristic curve showed an area beneath the curve of 0.877 +/- 0.06 for the
      Tobin index and 0.845 +/- 0.07 for maximum inspiratory pressure. CONCLUSION: The
      IMT intervention significantly increased maximum inspiratory pressure and
      significantly reduced the Tobin index; both measures are considered to be good
      extubation indices. IMT was associated with a reduction in noninvasive positive
      pressure time in the experimental group.

PMID- 23118534
TI  - Relationship between oxygen consumption kinetics and BODE Index in COPD patients.
AB  - BACKGROUND AND OBJECTIVE: Patients with chronic obstructive pulmonary disease
      (COPD) present with reduced exercise capacity due to impaired oxygen consumption
      (VO(2)), caused primarily by pulmonary dysfunction and deleterious peripheral
      adaptations. Assuming that COPD patients present with slower VO(2) and heart rate
      (HR) on-kinetics, we hypothesized that this finding is related to disease
      severity as measured by the BODE Index. In this context, the present study
      intends to evaluate the relationship between VO(2) uptake on-kinetics during high
      intensity exercise and the BODE Index in patients with COPD. METHODS: Twenty
      males with moderate-to-severe stable COPD and 13 healthy control subjects matched
      by age and sex were evaluated. COPD patients were screened by the BODE Index and
      then underwent an incremental cardiopulmonary exercise test and a constant speed
      treadmill session at 70% of maximal intensity for 6 minutes. The onset of the
      exercise (first 360 seconds) response for O(2) uptake and HR was modeled
      according to a monoexponential fit. RESULTS: Oxygen consumption and HR on
      kinetics were slower in the COPD group compared with controls. Additionally,
      VO(2) on-kinetic parameters revealed a strong positive correlation (r = 0.77, P <
      0.05) with BODE scores and a moderate negative correlation with walking distance
      (r = -0.45, P < 0.05). CONCLUSION: Our data show that moderate-to-severe COPD is
      related to impaired oxygen delivery and utilization during the onset of intense
      exercise.

PMID- 23118535
TI  - Randomized trial of pragmatic education for low-risk COPD patients: impact on
      hospitalizations and emergency department visits.
AB  - BACKGROUND: Most interventions aimed at reducing hospitalizations and emergency
      department (ED) visits in patients with chronic obstructive pulmonary disease
      (COPD) have employed resource-intense programs in high-risk individuals. Although
      COPD is a progressive disease, little is known about the effectiveness of
      proactive interventions aimed at preventing hospitalizations and ED visits in the
      much larger population of low-risk (no known COPD-related hospitalizations or ED
      visits in the prior year) patients, some of whom will eventually become high
      risk. METHODS: We tested the effect of a simple educational and self-efficacy
      intervention (n = 2243) versus usual care (n = 2182) on COPD/breathing-related ED
      visits and hospitalizations in a randomized study of low-risk patients at three
      Veterans Affairs (VA) medical centers in the upper Midwest. Administrative data
      was used to track VA admissions and ED visits. A patient survey was used to
      determine health-related events outside the VA. RESULTS: Rates of COPD-related VA
      hospitalizations in the education and usual care group were not significantly
      different (3.4 versus 3.6 admissions per 100 person-years, respectively; 95% CI
      of difference -1.3 to 1.0, P = 0.77). The much higher patient-reported rates of
      non-VA hospitalizations for breathing-related problems were lower in the
      education group (14.0 versus 19.0 per 100 person-years; 95% CI -8.6 to -1.4, P =
      0.006). Rates of COPD-related VA ED visits were not significantly different (6.8
      versus 5.3; 95% CI -0.1 to 3.0, P = 0.07), nor were non-VA ED visits (32.4 versus
      36.5; 95% CI -9.3 to 1.1, P = 0.12). All-cause VA admission and ED rates did not
      differ. Mortality rates (6.9 versus 8.3 per 100 person-years, respectively; 95%
      CI -3.0 to 0.4, P = 0.13) did not differ. CONCLUSION: An educational intervention
      that is practical for large numbers of low-risk patients with COPD may reduce the
      rate of breathing-related hospitalizations. Further research that more closely
      tracks hospitalizations to non-VA facilities is needed to confirm this finding.

PMID- 23118536
TI  - Profile of glycopyrronium for once-daily treatment of moderate-to-severe COPD.
AB  - Bronchodilators are central in the symptomatic management of chronic obstructive
      pulmonary disease (COPD). Long-acting muscarinic antagonists (LAMAs) and long
      acting beta(2)-agonists (LABAs) are the main classes of long-acting
      bronchodilators. To date, tiotropium is the only once-daily LAMA available for
      the treatment of COPD. Glycopyrronium is a novel LAMA, currently in development
      for COPD. Phase II studies have shown that glycopyrronium 50 MUg once daily
      provides clinically significant 24-hour bronchodilation with a rapid onset of
      action, which is faster than that of tiotropium, and a favorable safety and
      tolerability profile. The Phase III GLycopyrronium bromide in COPD airWays (GLOW)
      program has now confirmed the long-term efficacy and tolerability of
      glycopyrronium 50 MUg once daily. The three studies included in this program have
      further shown that the effect of glycopyrronium versus placebo is similar to that
      of tiotropium in reducing dyspnea and the risk of exacerbations, as well as
      improving lung function, exercise tolerance, and health status in patients with
      COPD. The safety profile of glycopyrronium is also similar to that of tiotropium
      in terms of overall incidence of adverse events and muscarinic side effects.
      Glycopyrronium could be an alternative choice to tiotropium, and like tiotropium,
      has the potential to be used as a monotherapy or combination therapy. Phase II
      studies have shown that a fixed-dose combination of glycopyrronium and the 24
      hour LABA indacaterol, produces rapid and sustained bronchodilation compared with
      indacaterol monotherapy in patients with COPD. Phase III studies are currently
      ongoing to assess the long-term efficacy and safety of this combination.

PMID- 23118537
TI  - Development and characterization of a novel nanoemulsion drug-delivery system for
      potential application in oral delivery of protein drugs.
AB  - BACKGROUND: The stability of protein drugs remains one of the key hurdles to
      their success in the market. The aim of the present study was to design a novel
      nanoemulsion drug-delivery system (NEDDS) that would encapsulate a standard-model
      protein drug--bovine serum albumin (BSA)--to improve drug stability. METHODS: The
      BSA NEDDS was prepared using a phase-inversion method and pseudoternary phase
      diagrams. The following characteristics were studied: morphology, size, zeta
      potential, drug loading, and encapsulation efficiency. We also investigated the
      stability of the BSA NEDDS, bioactivity of BSA encapsulated within the NEDDS, the
      integrity of the primary, secondary, and tertiary structures, and specificity.
      RESULTS: The BSA NEDDS consisted of Cremophor EL-35, propylene glycol, isopropyl
      myristate, and normal saline. The average particle diameter of the BSA NEDDS was
      about 21.8 nm, and the system showed a high encapsulation efficiency (>90%) and
      an adequate drug-loading capacity (45 mg/mL). The thermodynamic stability of the
      system was investigated at different temperatures and pH levels and in room
      temperature conditions for 180 days. BSA NEDDS showed good structural integrity
      and specificity for the primary, secondary, and tertiary structures, and good
      bioactivity of the loaded BSA. CONCLUSIONS: BSA NEDDS showed the properties of a
      good nanoemulsion-delivery system. NEDDS can greatly enhance the stability of the
      protein drug BSA while maintaining high levels of drug bioactivity, good
      specificity, and integrity of the primary, secondary, and tertiary protein
      structures. These findings indicate that the nanoemulsion is a potential
      formulation for oral administration of protein drugs.

PMID- 23118538
TI  - Enhancement of the dissolution rate and bioavailability of fenofibrate by a melt
      adsorption method using supercritical carbon dioxide.
AB  - BACKGROUND: The aim of this study was to enhance the bioavailability of
      fenofibrate, a poorly water-soluble drug, using a melt-adsorption method with
      supercritical CO(2). METHODS: Fenofibrate was loaded onto Neusilin((r)) UFL2 at
      different weight ratios of fenofibrate to Neusilin UFL2 by melt-adsorption using
      supercritical CO(2). For comparison, fenofibrate-loaded Neusilin UFL2 was
      prepared by solvent evaporation and hot melt-adsorption methods. The fenofibrate
      formulations prepared were characterized by differential scanning calorimetry,
      powder x-ray diffractometry, specific surface area, pore size distribution,
      scanning electron microscopy, and energy-dispersive x-ray spectrometry. In vitro
      dissolution and in vivo bioavailability were also investigated. RESULTS:
      Fenofibrate was distributed into the pores of Neusilin UFL2 and showed reduced
      crystal formation following adsorption. Supercritical CO(2) facilitated the
      introduction of fenofibrate into the pores of Neusilin UFL2. Compared with raw
      fenofibrate, fenofibrate from the prepared powders showed a significantly
      increased dissolution rate and better bioavailability. In particular, the area
      under the drug concentration-time curve and maximal serum concentration of the
      powders prepared using supercritical CO(2) were 4.62-fold and 4.52-fold greater
      than the corresponding values for raw fenofibrate. CONCLUSION: The results of
      this study highlight the usefulness of the melt-adsorption method using
      supercritical CO(2) for improving the bioavailability of fenofibrate.

PMID- 23118539
TI  - Biocompatibility of chitosan-coated iron oxide nanoparticles with osteoblast
      cells.
AB  - BACKGROUND: Bone disorders (including osteoporosis, loosening of a prosthesis,
      and bone infections) are of great concern to the medical community and are
      difficult to cure. Therapies are available to treat such diseases, but all have
      drawbacks and are not specifically targeted to the site of disease. Chitosan is
      widely used in the biomedical community, including for orthopedic applications.
      The aim of the present study was to coat chitosan onto iron oxide nanoparticles
      and to determine its effect on the proliferation and differentiation of
      osteoblasts. METHODS: Nanoparticles were characterized using transmission
      electron microscopy, dynamic light scattering, x-ray diffraction, zeta potential,
      and vibrating sample magnetometry. Uptake of nanoparticles by osteoblasts was
      studied by transmission electron microscopy and Prussian blue staining. Viability
      and proliferation of osteoblasts were measured in the presence of uncoated iron
      oxide magnetic nanoparticles or those coated with chitosan. Lactate
      dehydrogenase, alkaline phosphatase, total protein synthesis, and extracellular
      calcium deposition was studied in the presence of the nanoparticles. RESULTS:
      Chitosan-coated iron oxide nanoparticles enhanced osteoblast proliferation,
      decreased cell membrane damage, and promoted cell differentiation, as indicated
      by an increase in alkaline phosphatase and extracellular calcium deposition.
      Chitosan-coated iron oxide nanoparticles showed good compatibility with
      osteoblasts. CONCLUSION: Further research is necessary to optimize magnetic
      nanoparticles for the treatment of bone disease.

PMID- 23118540
TI  - Can a physician predict the clinical response to first-line immunomodulatory
      treatment in relapsing-remitting multiple sclerosis?
AB  - BACKGROUND: Decreased relapse rate and slower disease progression have been
      reported with long-term use of immunomodulatory treatments (IMTs, interferon beta
      or glatiramer acetate) in relapsing-remitting multiple sclerosis. There are,
      however, patients who do not respond to such treatments, and they can be
      potential candidates for alternative therapeutic approaches. OBJECTIVE: To
      identify clinical factors as possible predictors of poor long-term response.
      METHODS: A 9-year prospective, continuous follow-up at a single center in Hungary
      to assess clinical efficacy of IMT. RESULTS: In a patient group of 81 subjects
      with mean IMT duration of 54 +/- 33 months, treatment efficacy expressed as
      annual relapse rate and change in clinical severity from baseline did not depend
      on the specific IMT (any of the interferon betas or glatiramer acetate), and on
      mono- or multifocal features of the initial appearance of the disease. Responders
      had shorter disease duration and milder clinical signs at the initiation of
      treatment. Relapse-rate reduction in the initial 2 years of treatment predicted
      clinical efficacy in subsequent years. CONCLUSION: Based on these observations,
      we suggest that a 2-year trial period is sufficient to decide on the efficacy of
      a specific IMT. For those with insufficient relapse reduction in the first 2
      years of treatment, a different IMT or other therapeutic approaches should be
      recommended.

PMID- 23118541
TI  - Effectiveness of sensory processing strategies on activity level in inclusive
      preschool classrooms.
AB  - BACKGROUND: The purpose of this study was to investigate the effectiveness of
      sensory processing strategies in improving the activity level of children with
      sensory integration dysfunction. METHODS: The study used a matching-only pretest
      posttest control group design, which requires random matching of sensory
      integration dysfunction to the corresponding intervention group (n = 18) and
      control group (n = 18). The intervention group comprised 3-6-year-old children
      who received an 8-week school-day intervention during implementation of the theme
      curriculum. RESULTS: The 8-week treatment significantly reduced the activity
      level and foot-swinging episodes in children with sensory integration
      dysfunction, and obtained a medium-effect size. However, the level of improvement
      in the control group did not show any statistically significant change.
      CONCLUSION: Sensory processing strategies could improve activity levels in
      children with sensory integration dysfunction. However, this study was unable to
      exclude a developmental effect. The social validity results show that sensory
      processing strategies can be integrated into the theme curriculum and improve
      activity levels in children.

PMID- 23118542
TI  - Outcomes analysis of Internet-based CME initiatives for diagnosis and treatment
      of fibromyalgia patients: transition from education to physician behavior to
      patient health.
AB  - A well designed outcomes research study was performed in which 20 primary care
      physicians were selected to participate. Each physician had more than 30
      fibromyalgia patients in their practice. The study design consisted of four
      phases. In phase one, physicians undertook a self-assessment of their practice.
      Phase two of the study involved diagnosis and treatment of a virtual case
      vignette. The third phase consisted of analysis of the data from phase two and
      providing feedback from an expert rheumatologist, and the fourth phase was to
      complete patient report forms for five patients in their practice. The year-long
      study was completed by 12 physicians and resulted in data on 60 patients. The
      results of this study provide an insight into how physicians are diagnosing and
      treating patients with fibromyalgia. In this study, we transition from continuing
      medical education to physician behavior to patient outcomes.

PMID- 23118543
TI  - Effects of repetitive transcranial magnetic stimulation on clinical, social, and
      cognitive performance in postpartum depression.
AB  - BACKGROUND: This randomized, placebo-controlled, double-blind pilot study
      evaluated the impact of repetitive transcranial magnetic stimulation (rTMS) on
      clinical, cognitive, and social performance in women suffering with postpartum
      depression. METHODS: Fourteen patients were randomized to receive 20 sessions of
      sham rTMS or active 5 Hz rTMS over the left dorsolateral prefrontal cortex.
      Psychiatric clinical scales and a neuropsychological battery were applied at
      baseline (pretreatment), week 4 (end of treatment), and week 6 (follow-up,
      posttreatment week 2). RESULTS: The active rTMS group showed significant
      improvement 2 weeks after the end of rTMS treatment (week 6) in Hamilton
      Depression Rating Scale (P = 0.020), Global Assessment Scale (P = 0.037),
      Clinical Global Impression (P = 0.047), and Social Adjustment Scale-Self Report
      Work at Home (P = 0.020). CONCLUSION: This study suggests that rTMS has the
      potential to improve the clinical condition in postpartum depression, while
      producing marginal gains in social and cognitive function.

PMID- 23118545
TI  - Adverse incidents resulting in exposure to body fluids at a UK dental teaching
      hospital over a 6-year period.
AB  - BACKGROUND: The safety and protection of patients and health care workers is of
      paramount importance in dentistry, and this includes students in training who
      provide clinical care. Given the nature of dental care, adverse incidents can and
      do occur, exposing health care workers to body fluids and putting them at risk of
      infection, including contracting a blood-borne virus. The aim of this research
      was to analyze trends in the volume, rate, nature, management, and outcome of
      adverse incidents reported at one dental teaching hospital from 2005 to 2010.
      METHODS: Descriptive analysis of trends in the volume, rate, nature, management,
      and outcome of adverse incidents reported at one dental teaching hospital over a
      six-year period was undertaken in relation to the level of outpatient and day
      surgery activity. RESULTS: In total, 287 incidents were reported over a six-year
      period, which amounted to 0.039% of outpatient or day surgery appointments.
      Nearly three quarters of all the incidents (n = 208, 72%) took place during
      treatment or whilst clearing away after the appointment. The most frequent
      incidents were associated with administration of local anesthetic (n = 63, 22%),
      followed by burs used in dental hand pieces (n = 51, 18%). CONCLUSION: This
      research confirms that adverse incidents are a feature of dental hospitals and
      reports the common sources. The importance of accurate and consistent reporting
      of data to ensure that these issues are monitored to inform action and reduce
      risks to staff, students, and patients are highlighted.

PMID- 23118544
TI  - Current and emerging treatment options for nasopharyngeal carcinoma.
AB  - In this article, we focus on the current and emerging treatments in
      nasopharyngeal cancer (NPC). A detailed evolution of the current standard of
      care, and new techniques and treatment options will be reviewed. Intergroup 0099
      established the role for chemoradiotherapy (chemo-RT) in the treatment of
      nasopharyngeal carcinoma. Multiple randomized Phase III trials have shown the
      benefit of chemo-RT; however, none of these studies utilized modern radiotherapy
      (RT) techniques of intensity-modulated radiation therapy (IMRT). IMRT has the
      ability to deliver high doses of radiation to the target structures while sparing
      adjacent bystander healthy tissues, and has now become the preferred RT treatment
      modality. Chemotherapy also has had a shifting paradigm of induction and/or
      adjuvant chemotherapy combined with RT alone, to the investigation with
      concurrent chemo-RT. New treatment options including targeted monoclonal
      antibodies and small molecule tyrosine kinase inhibitors are being studied in
      NPC. These new biologic therapies have promising in vitro activity for NPC, and
      emerging clinical studies are beginning to define their role. RT continues to
      expand its capabilities, and since IMRT and particle therapy, specifically
      intensity-modulated proton therapy (IMPT), has reports of impressive dosimetric
      efficacy in-silica. Adaptive RT is attempting to reduce toxicity while
      maintaining treatment efficacy, and the clinical results are still in their
      youth. Lastly, Epstein- Barr virus (EBV) DNA has recently been studied for
      prediction of tumor response and its use as a biomarker is increasingly promising
      to aid in early detection as well as supplementing the current staging system. RT
      with or without chemotherapy remains the standard of care for nasopharyngeal
      carcinoma. Advances in RT technique, timing of chemotherapy, biologically
      targeted agents, particle therapy, adaptive RT, and the incorporation of EBV DNA
      as a biomarker may aid in the current and future treatment of nasopharyngeal
      cancer.

PMID- 23118546
TI  - Association of ADIPOQ +45T>G polymorphism with body fat mass and blood levels of
      soluble adiponectin and inflammation markers in a Mexican-Mestizo population.
AB  - PURPOSE: Obesity is a disease with genetic susceptibility characterized by an
      increase in storage and irregular distribution of body fat. In obese patients,
      the decrease in the Adiponectin gene (ADIPOQ) expression has been associated with
      a systemic low-grade inflammatory state. Our aim was to investigate the
      relationship between ADIPOQ +45T>G gene simple nucleotide polymorphism (SNP
      rs2241766) with serum adiponectin (sAdiponectin), distribution of body fat
      storage, and inflammation markers. SUBJECTS AND METHODS: In this cross-sectional
      study, 242 individuals from Western Mexico characterized as Mexican-Mestizo and
      classified by body mass index (BMI), were included. Anthropometrics, body
      composition, body fat distribution, and inflammation markers were measured by
      routine methods. Genotypes were characterized using the polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) technique and sAdiponectin by
      the ELISA method. A P-value <0.05 was considered the statistically significant
      threshold. RESULTS: sAdiponectin is associated with BMI (P < 0.001) and the
      genotypes (P < 0.001 to 0.0046) GG (8169 +/- 1162 ng/mL), TG (5189 +/- 501
      ng/mL), and TT (3741 +/- 323 ng/mL), but the SNP ADIPOQ +45T>G is not associated
      with BMI. However, the detailed analysis showed association of this SNP with a
      pattern of fat distribution and correlations (P < 0.05) with inflammation markers
      and distribution of body fat storage (Pearson's r = -0.169 to -0.465) were found.
      CONCLUSION: In this study, we have suggested that the ADIPOQ +45G allele could be
      associated with distribution of body fat storage in obesity. On the other hand,
      as no association was observed between ADIPOQ +45T>G gene polymorphism and
      obesity, it cannot be concluded that the ADIPOQ +45G allele is responsible for
      the increase of adiponectin levels.

PMID- 23118547
TI  - Alcohol mixed with energy drinks: methodology and design of the Utrecht Student
      Survey.
AB  - This paper describes the methodology of the Utrecht Student Survey. This online
      survey was conducted in June 2011 by 6002 students living in Utrecht, The
      Netherlands. The aim of the survey was to determine the potential impact of
      mixing alcoholic beverages with energy drinks on overall alcohol consumption and
      alcohol-related consequences. In contrast to most previous surveys conducted on
      this topic, the current survey used a more appropriate within-subject design,
      comparing the alcohol consumption of individuals who consume alcohol mixed with
      energy drinks on occasions. Specifically, a comparison was conducted to examine
      the occasions during which these individuals consume this mixture versus
      occasions during which they consume alcohol alone. In addition to energy drinks,
      the consumption of other non-alcoholic mixers was also assessed when combined
      with alcoholic beverages. Furthermore, the reasons for consuming energy drinks
      alone or in combination with alcohol were investigated, and were compared to
      reasons for mixing alcohol with other non-alcoholic beverages. Finally,
      personality characteristics and the level of risk-taking behavior among the
      individuals were also assessed to explore their relationship with alcohol
      consumption. The Utrecht Student Survey will be replicated in the USA, Australia,
      and the UK. Results will be pooled, but also examined for possible cross-cultural
      differences.

PMID- 23118548
TI  - Good clinical practice in dubious head trauma - the problem of retained
      intracranial foreign bodies.
AB  - OBJECTIVE: In young people, traumatic head and brain injuries are the leading
      cause of morbidity and mortality. In some cases, no neurological deficits are
      present, even after penetrating trauma. These patients have a greater risk of
      suffering from secondary injuries due to secondary infections, brain edema, and
      hematomas. We present a case report which illustrates that brain injuries that do
      not induce neurological deficits can still result in a fatal clinical course and
      death, with medicolegal consequences. CLINICAL PRESENTATION: A 19-year-old
      patient was admitted to hospital suffering from a head injury due to an assault.
      He reported that he was attacked from behind. Medical examination showed no
      neurological deficits, and only a small occipital wound. Neuroimaging of the
      cranium revealed that a knife blade was penetrating the cranial bone and touching
      the superior sagittal sinus. INTERVENTION: After removing the foreign body,
      magnetic resonance imaging showed that the superior sagittal sinus remained open.
      CONCLUSION: We want to stress that possible problems can arise due to the
      retention of objects in the cranium, while also highlighting the risk of
      superficial clinical examination.

PMID- 23118549
TI  - Hepatitis C virus infection and autoimmune diseases.
AB  - Hepatitis C virus (HCV) infection is associated with a number of extrahepatic
      disorders. The most studied conditions associated with HCV are type II mixed
      cryoglobulinemia and B cell lymphoma. However, many reports suggest that HCV
      might also be associated with a number of autoimmune disorders, both organ
      specific and not organ-specific. Although concomitant treatment of HCV infection
      is a confounding factor when ascertaining the actual role of HCV in inducing
      autoimmune disease, a considerable amount of experimental data indicates that HCV
      is able to subvert the immune system and consequently induce autoimmunity. In the
      present review, we report a series of observations which associate chronic HCV
      infection with the onset of autoimmune disorders.

PMID- 23118550
TI  - Does going to an amusement park alleviate low back pain? A preliminary study.
AB  - BACKGROUND: Low back pain is often called nonspecific pain. In this type of low
      back pain, various emotions and stress are known to strongly affect pain
      perception. The purpose of this study is to investigate how the degree of low
      back pain changes in people with chronic mild low back pain when they are inside
      and outside of an amusement park where people are supposed to have physical and
      psychological enjoyment. METHODS: The subjects were 23 volunteers (13 males and
      10 females) aged 18 to 46 years old with a mean age of 24.0 years who had chronic
      low back pain. Visual analog scale (VAS) scores of low back pain and salivary
      amylase levels (kIU/L) of all subjects were measured at five time points:
      immediately after getting on the bus heading for the amusement park; 10 minutes,
      1 hour (immediately after boarding the roller coaster), and 3 hours (immediately
      after exiting the haunted house) after arriving at the amusement park; and
      immediately before getting off the bus returning from the park. RESULTS: The
      three VAS values in the amusement park (10 minutes, 1 hour, and 3 hours after
      arriving at the amusement park) measured were significantly lower (P < 0.05) when
      compared with the other two values measured immediately after getting on the bus
      heading for the amusement park and immediately before getting off the return bus.
      In salivary amylase levels, there were no statistically significant differences
      among the values measured at the five time points. CONCLUSION: Low back pain was
      significantly alleviated when the subjects were in the amusement park, which
      demonstrated that enjoyable activities, though temporarily, alleviated their low
      back pain.

PMID- 23118551
TI  - Increase in the proportion of patients hospitalized with acute myocardial
      infarction with do-not-resuscitate orders already in place between 2001 and 2007:
      a nonconcurrent prospective study.
AB  - BACKGROUND AND OBJECTIVE: Shared decision making and advance planning in end-of
      life decisions have become increasingly important aspects of the management of
      seriously ill patients. Here, we describe the use and timing of do-not
      resuscitate (DNR) orders in patients hospitalized with acute myocardial
      infarction (AMI). STUDY DESIGN AND SETTING: The nonconcurrent prospective study
      population consisted of 4182 patients hospitalized with AMI in central
      Massachusetts in four annual periods between 2001 and 2007. RESULTS: One-quarter
      (25%) of patients had a DNR order written either prior to or during
      hospitalization. The frequency of DNR orders remained constant (24% in 2001; 26%
      in 2007). Among patients with DNR orders, there was a significant increase in
      orders written prior to hospitalization (2001: 9%; 2007: 55%). Older patients and
      those with a medical history of heart failure or myocardial infarction were more
      likely to have prior DNR orders than respective comparison groups. Patients with
      prior DNR orders were less likely to die 1 month after hospitalization than
      patients whose DNRs were written during hospitalization. CONCLUSION: Although the
      use of DNR orders in patients hospitalized with AMI was stable during the period
      under study, in more recent years, patients are increasingly being hospitalized
      with DNR orders already in place.

PMID- 23118552
TI  - Effect of intensity of unconditional stimulus on reconsolidation of contextual
      fear memory.
AB  - Memory reconsolidation is ubiquitous across species and various memory tasks. It
      is a dynamic process in which memory is modified and/or updated. In experimental
      conditions, memory reconsolidation is usually characterized by the fact that the
      consolidated memory is disrupted by a combination of memory reactivation and
      inhibition of protein synthesis. However, under some experimental conditions, the
      reactivated memory is not disrupted by inhibition of protein synthesis. This so
      called "boundary condition" of reconsolidation may be related to memory strength.
      In Pavlovian fear conditioning, the intensity of unconditional stimulus (US)
      determines the strength of the fear memory. In this study, we examined the effect
      of the intensity of US on the reconsolidation of contextual fear memory. Strong
      contextual fear memory, which is conditioned with strong US, is not disrupted by
      inhibition of protein synthesis after its reactivation; however, a weak fear
      memory is often disrupted. This suggests that a US of strong intensity can
      inhibit reconsolidation of contextual fear memory.

PMID- 23118553
TI  - High k(+)-induced relaxation by nitric oxide in human gastric fundus.
AB  - This study was designed to elucidate high K(+)-induced relaxation in the human
      gastric fundus. Circular smooth muscle from the human gastric fundus greater
      curvature showed stretch-dependent high K(+) (50 mM)-induced contractions.
      However, longitudinal smooth muscle produced stretch-dependent high K(+)-induced
      relaxation. We investigated several relaxation mechanisms to understand the
      reason for the discrepancy. Protein kinase inhibitors such as KT 5823 (1 uM) and
      KT 5720 (1 uM) which block protein kinases (PKG and PKA) had no effect on high
      K(+)-induced relaxation. K(+) channel blockers except 4-aminopyridine (4-AP), a
      voltage-dependent K(+) channel (K(V)) blocker, did not affect high K(+)-induced
      relaxation. However, N(G)-nitro-L-arginine and 1H-(1,2,4)oxadiazolo (4,3
      A)quinoxalin-1-one, an inhibitors of soluble guanylate cyclase (sGC) and 4-AP
      inhibited relaxation and reversed relaxation to contraction. High K(+)-induced
      relaxation of the human gastric fundus was observed only in the longitudinal
      muscles from the greater curvature. These data suggest that the longitudinal
      muscle of the human gastric fundus greater curvature produced high K(+)-induced
      relaxation that was activated by the nitric oxide/sGC pathway through a K(V)
      channel-dependent mechanism.

PMID- 23118554
TI  - The Protective Effect of Eupatilin against Hydrogen Peroxide-Induced Injury
      Involving 5-Lipoxygenase in Feline Esophageal Epithelial Cells.
AB  - In this study, we focused to identify whether eupatilin (5,7-dihydroxy-3',4',6
      trimethoxyflavone), an extract from Artemisia argyi folium, prevents H(2)O(2)
      induced injury of cultured feline esophageal epithelial cells. Cell viability was
      measured by the conventional MTT reduction assay. Western blot analysis was
      performed to investigate the expression of 5-lipoxygenase by H(2)O(2) treatment
      in the absence and presence of inhibitors. When cells were exposed to 600 uM
      H(2)O(2) for 24 hours, cell viability was decreased to 40%. However, when cells
      were pretreated with 25~150 uM eupatilin for 12 hours, viability was
      significantly restored in a concentration-dependent manner. H(2)O(2)-treated
      cells were shown to express 5-lipoxygenase, whereas the cells pretreated with
      eupatilin exhibited reduction in the expression of 5-lipoxygenase. The H(2)O(2)
      induced increase of 5-lipoxygenase expression was prevented by SB202190,
      SP600125, or NAC. We further demonstrated that the level of leukotriene B(4)
      (LTB(4)) was also reduced by eupatilin, SB202190, SP600125, NAC, or
      nordihydroguaiaretic acid (a lipoxygenase inhibitor) pretreatment. H(2)O(2)
      induced the activation of p38MAPK and JNK, this activation was inhibited by
      eupatilin. These results indicate that eupatilin may reduce H(2)O(2)-induced
      cytotoxicity, and 5-lipoxygenase expression and LTB(4) production by controlling
      the p38 MAPK and JNK signaling pathways through antioxidative action in feline
      esophageal epithelial cells.

PMID- 23118555
TI  - Antiproliferative and cytotoxic effects of resveratrol in mitochondria-mediated
      apoptosis in rat b103 neuroblastoma cells.
AB  - Resveratrol, a natural compound, has been shown to possess anti-cancer, anti
      aging, anti-inflammatory, anti-microbial, and neuroprotective activities. In this
      study, we examined the antiproliferative and cytotoxicity properties of
      resveratrol in Rat B103 neuroblastoma cells; although it's molecular mechanisms
      for the biological effects are not fully defined. Here, we examined the cellular
      cytotoxicity of resveratrol by cell viability assay, antiproliferation by BrdU
      assay, DNA fragmentation by DNA ladder assay, activation of caspases and Bcl-2
      family proteins were detected by western blot analyses. The results of our
      investigation suggest that resveratrol increased cellular cytotoxicity of Rat
      B103 neuroblastoma cells in a dose-and time-dependent manner with IC(50) of 17.86
      uM at 48 h. On the other hand, incubation of neuroblastoma cells with resveratrol
      resulted in S-phase cell cycle arrests which dose-dependently and significantly
      reduced BrdU positive cells through the downregulation of cyclin D1 protein. In
      addition, resveratrol dose-dependently and significantly downregulated the
      expression of anti-apoptotic protein includes Bcl-2, Bcl-xL and Mcl-1 and also
      activates cleavage caspase-9 and-3 via the downregulation of procaspase-9 and -3
      in a dose-dependent manner which indicates that involvement of intrinsic
      mitochondria-mediated apoptotic pathway. In conclusion, resveratrol increases
      cellular cytotoxicity and inhibits the proliferation of B103 neuroblastoma cells
      by inducing mitochondria-mediated intrinsic caspase dependent pathway which
      suggests this natural compound could be used as therapeutic purposes for
      neuroblastoma malignancies.

PMID- 23118556
TI  - Wide spectrum of inhibitory effects of sertraline on cardiac ion channels.
AB  - Sertraline is a commonly used antidepressant of the selective serotonin reuptake
      inhibitors (SSRIs) class. In these experiments, we have used the whole cell patch
      clamp technique to examine the effects of sertraline on the major cardiac ion
      channels expressed in HEK293 cells and the native voltage-gated Ca(2+) channels
      in rat ventricular myocytes. According to the results, sertraline is a potent
      blocker of cardiac K(+) channels, such as hERG, I(Ks) and I(K1). The rank order
      of inhibitory potency was hERG >I(K1)> I(Ks) with IC(50) values of 0.7, 10.5, and
      15.2 uM, respectively. In addition to K(+) channels, sertraline also inhibited
      I(Na) and I(Ca), and the IC(50) values are 6.1 and 2.6 uM, respectively.
      Modification of these ion channels by sertraline could induce changes of the
      cardiac action potential duration and QT interval, and might result in cardiac
      arrhythmia.

PMID- 23118557
TI  - cAMP/PKA Agonist Restores the Fasting-Induced Down-Regulation of nNOS Expression
      in the Paraventricular Nucleus.
AB  - Gene expression of neuronal nitric oxide synthase (nNOS) changes in the
      hypothalamic paraventricular nucleus (PVN) depending on feeding conditions, which
      is decreased during food deprivation and restored by refeeding, and
      phosphorylated cAMP response element binding protein (pCREB) was suggested to
      play a role in its regulation. This study was conducted to examine if the fasting
      induced down-regulation of the PVN-nNOS expression is restored by activation of
      cAMP-dependent protein kinase A (cAMP/PKA) pathway. Freely moving rats received
      intracerebroventricular (icv) injection of cAMP/PKA activator Sp-cAMP (40 nmol)
      or vehicle (sterilized saline) following 48 h of food deprivation. One hour after
      drug injections, rats were transcardially perfused with 4% paraformaldehyde, and
      the PVN tissues were processed for nNOS or pCREB immunohistochemistry. Sp-cAMP
      significantly increased not only nNOS but also pCREB immunoreactivities in the
      PVN of food deprived rats. Fasting-induced down-regulation of the PVN-nNOS was
      restored by 1 h after the icv Sp-cAMP. Results suggest that cAMP/PKA pathway may
      mediate the regulation of the PVN-nNOS expression depending on different feeding
      conditions.

PMID- 23118558
TI  - Genetic Polymorphisms of Cytochrome P450 2C19 in Functional Dyspeptic Patients
      Treated with Cimetidine.
AB  - Inter-individual pharmacokinetic variation of H(2)-receptor antagonist is related
      to genetic polymorphism of CYP2C19. We investigated the frequency of CYP2C19
      genetic polymorphism and the treatment duration of cimetidine by CYP2C19
      genotypes in functional dyspeptic patients without definite causes who were
      treated with cimetidine in Korea. One hundred subjects with functional dyspepsia
      participated in this study from March 1, 2010 to June 30, 2011. They were tested
      by upper gastrointestinal endoscopy and treated for their dyspepsia with
      cimetidine. The single nucleotide polymorphisms (SNPs) of CYP2C19 were genotyped
      using the Seeplex CYP2C19 ACE Genotyping system. There were no significant
      differences in the demographic, clinical, or laboratory findings among the
      CYP2C19 subgroups which are wild type homozygote (W/W), heterozygote (W/V), and
      variant homozygote (V/V). The frequencies of CYP2C19 subgroups were 33 (33%) in
      W/W, 49 (49%) in W/V, and 18 (18%) in V/V, respectively. The mean duration of
      cimetidine treatment (in weeks) was the shortest in the V/V among the CYP2C19
      genotypes (W/W: 5.1+/-1.5, W/V: 4.0+/-1.7, V/V: 2.1+/-0.7; p<0.001). This study
      can also act as a basis for further investigation to identify the underlying
      genetic, epigenetic, or environmental factors in CYP2C19 enzyme activity.

PMID- 23118559
TI  - Sustained K(+) Outward Currents are Sensitive to Intracellular Heteropodatoxin2
      in CA1 Neurons of Organotypic Cultured Hippocampi of Rats.
AB  - Blocking or regulating K(+) channels is important for investigating neuronal
      functions in mammalian brains, because voltage-dependent K(+) channels (Kv
      channels) play roles to regulate membrane excitabilities for synaptic and somatic
      processings in neurons. Although a number of toxins and chemicals are useful to
      change gating properties of Kv channels, specific effects of each toxin on a
      particular Kv subunit have not been sufficiently demonstrated in neurons yet. In
      this study, we tested electrophysiologically if heteropodatoxin2 (HpTX(2)), known
      as one of Kv4-specific toxins, might be effective on various K(+) outward
      currents in CA1 neurons of organotypic hippocampal slices of rats. Using a
      nucleated-patch technique and a pre-pulse protocol in voltage-clamp mode, total
      K(+) outward currents recorded in the soma of CA1 neurons were separated into two
      components, transient and sustained currents. The extracellular application of
      HpTX(2) weakly but significantly reduced transient currents. However, when
      HpTX(2) was added to internal solution, the significant reduction of amplitudes
      were observed in sustained currents but not in transient currents. This indicates
      the non-specificity of HpTX(2) effects on Kv4 family. Compared with the effect of
      cytosolic 4-AP to block transient currents, it is possible that cytosolic HpTX(2)
      is pharmacologically specific to sustained currents in CA1 neurons. These results
      suggest that distinctive actions of HpTX(2) inside and outside of neurons are
      very efficient to selectively reduce specific K(+) outward currents.

PMID- 23118560
TI  - CTLA-4-Tg/CD-28-KO Mice Exhibit Reduced T Cell Proliferation in vivo Compared to
      CD-28-KO Mice in a Graft-versus-host Disease Model.
AB  - Activated T cells express inhibitory receptors such as CTLA-4 that can
      downregulate immune responses. Blockade of or genetic deficiency in CTLA-4 can
      result in autoimmunity. Therefore, strategies to increase the inhibitory function
      of CTLA-4 may be attractive in settings of undesirable T cell responses such as
      autoimmunity or transplant rejection. We have tested the hypothesis that
      transgenic constitutive expression of CTLA-4 can further attenuate immune
      responses when compared with normal inducible expression. Our results indicate
      that transgenic expression of CTLA-4 in mouse T cells (CTLA-4-Tg T cells) results
      in reduced cell cycle progression and increased apoptosis of TCR-stimulated T
      cells. CTLA-4-Tg T cells display reduced T cell proliferation in an in vivo model
      of graft versus host disease (GVHD). These results further our understanding of
      how CTLA-4 can be manipulated to inhibit immune responses and may help
      development of new therapeutic strategies for clinical settings of autoimmunity
      and transplantation.

PMID- 23118561
TI  - Simultaneous Determination of Glutamate, Glycine, and Alanine in Human Plasma
      Using Precolumn Derivatization with 6-Aminoquinolyl-N-hydroxysuccinimidyl
      Carbamate and High-Performance Liquid Chromatography.
AB  - A simple, sensitive and reproducible high-performance liquid chromatography
      (HPLC) method has been validated for determining concentrations of glutamate,
      glycine, and alanine in human plasma. Proteins in plasma were precipitated with
      perchloric acid, followed by derivatization with 6-aminoquinolyl-N
      hydroxysuccinimidyl carbamate (AQC). Simultaneous analysis of glutamate, glycine,
      and alanine is achieved using reversed-phase HPLC conditions and ultraviolet
      detection. Excellent linearity was observed for these three amino acids over
      their concentration ranges with correlation coefficients (r)>0.999. The intra-
      and inter-day precision were below 10%. This method utilizes quality control
      samples and demonstrates excellent plasma recovery and accuracy. The developed
      method has been successfully applied to measure plasma glutamate, glycine, and
      alanine in twenty volunteers.

PMID- 23118562
TI  - Gecko Proteins Exert Anti-Tumor Effect against Cervical Cancer Cells Via PI3
      Kinase/Akt Pathway.
AB  - Anti-tumor activity of the proteins from Gecko (GP) on cervical cancer cells, and
      its signaling mechanisms were assessed by viable cell counting, propidium iodide
      (PI) staining, and Western blot analysis. GP induced the cell death of HeLa cells
      in a dose-dependent manner while it did not affect the viability of normal cells.
      Western blot analysis showed that GP decreased the activation of Akt, and co
      administration of GP and Akt inhibitors synergistically exerted anti-tumor
      activities on HeLa cells, suggesting the involvement of PI3-kinase/Akt pathway in
      GP-induced cell death of the cancer cells. Indeed, the cytotoxic effect of GP
      against HeLa cells was inhibited by overexpression of constituvely active form of
      Akt in HeLa cells. The candidates of the functional proteins in GP were analyzed
      by Mass-spectrum. Taken together, our results suggest that GP elicits anti-tumor
      activity against HeLa cells by inhibition of PI3-kinase/Akt pathway.

PMID- 23118563
TI  - Retraction: A Novel Carbamoyloxy Arylalkanoyl Arylpiperazine Compound (SKL-NP)
      Inhibits Hyperpolarization-Activated Cyclic Nucleotide-Gated (HCN) Channel
      Currents in Rat Dorsal Root Ganglion Neurons.

PMID- 23118564
TI  - Evaluation of anterior ethmoidal artery by 320-slice CT angiography with
      comparison to three-dimensional spin digital subtraction angiography: initial
      experiences.
AB  - OBJECTIVE: To explore the usefulness of 320-slice CT angiography (CTA) for
      evaluating the course of the anterior ethmoidal artery (AEA) and its relationship
      with adjacent structures by using three-dimensional (3D) spin digital subtraction
      angiography (DSA) as standard reference. MATERIALS AND METHODS: From December
      2008 to December 2010, 32 patients with cerebrovascular disease, who underwent
      both cranial 3D spin DSA and 320-slice CTA within a 30 day period from each
      other, were retrospectively reviewed. AEA course in ethmoid was analyzed in DSA
      and CTA. In addition, adjacent bony landmarks (bony notch in medial orbital wall,
      anterior ethmoidal canal, and anterior ethmoidal sulcus) were evaluated with CTA
      using the MPR technique oriented along the axial, coronal and oblique coronal
      planes in all patients. The dose length product (DLP) for CTA and the dose-area
      product (DAP) for 3D spin DSA were recorded. Effective dose (ED) was calculated.
      RESULTS: The entire course of the AEA was seen in all 32 cases (100%) with 3D
      spine DSA and in 29 of 32 cases (90.1%) with 320-slice CTA, with no significant
      difference (p = 0.24). In three cases where AEA was not visualized on 320-slice
      CTA, two were due to the dominant posterior ethmoidal artery, while the remaining
      case was due to diminutive AEA. On MPR images of 320-slice CT, a bony notch in
      the orbital medial walls was detected in all cases (100%, 64 of 64); anterior
      ethmoidal canal was seen in 28 of 64 cases (43.8%), and the anterior ethmoidal
      sulcus was seen in 63 of 64 cases (98.4%). The mean effective dose in CTA was 0.6
      +/- 0.25 mSv, which was significantly lower than for 3D spin DSA (1.3 +/- 0.01
      mSv) (p < 0.001). CONCLUSION: 320-slice CTA has a similar detection rate for AEA
      to that of 3D spin DSA; however, it is noninvasive, and may be preferentially
      used for the evaluation of AEA and its adjacent bony variations and pathologic
      changes in preoperative patients with paranasal sinus diseases.

PMID- 23118565
TI  - Fluid-attenuated inversion recovery hypointensity of the pulvinar nucleus of
      patients with Alzheimer disease: its possible association with iron accumulation
      as evidenced by the t2(*) map.
AB  - OBJECTIVE: We hypothesized that prominent pulvinar hypointensity in brain MRI
      represents the disease process due to iron accumulation in Alzheimer disease
      (AD). We aimed to determine whether or not the pulvinar signal intensity (SI) on
      the fluid-attenuated inversion recovery (FLAIR) sequences at 3.0T MRI differs
      between AD patients and normal subjects, and also whether the pulvinar SI is
      correlated with the T2(*) map, an imaging marker for tissue iron, and a cognitive
      scale. MATERIALS AND METHODS: Twenty one consecutive patients with AD and 21 age
      matched control subjects were prospectively included in this study. The pulvinar
      SI was assessed on the FLAIR image. We measured the relative SI ratio of the
      pulvinar to the corpus callosum. The T2(*) values were calculated from the T2(*)
      relaxometry map. The differences between the two groups were analyzed, by using a
      Student t test. The correlation between the measurements was assessed by the
      Pearson's correlation test. RESULTS: As compared to the normal white matter, the
      FLAIR signal intensity of the pulvinar nucleus was significantly more hypointense
      in the AD patients than in the control subjects (p < 0.01). The pulvinar T2(*)
      was shorter in the AD patients than in the control subjects (51.5 +/- 4.95 ms vs.
      56.5 +/- 5.49 ms, respectively, p = 0.003). The pulvinar SI ratio was strongly
      correlated with the pulvinar T2(*) (r = 0.745, p < 0.001). When controlling for
      age, only the pulvinar-to-CC SI ratio was positively correlated with that of the
      Mini-Mental State Examination (MMSE) score (r = 0.303, p < 0.050). Conversely,
      the pulvinar T2(*) was not correlated with the MMSE score (r = 0.277, p = 0.080).
      CONCLUSION: The FLAIR hypointensity of the pulvinar nucleus represents an
      abnormal iron accumulation in AD and may be used as an adjunctive finding for
      evaluating AD.

PMID- 23118566
TI  - Prospectively electrocardiogram-gated high-pitch spiral acquisition mode dual
      source CT coronary angiography in patients with high heart rates: comparison with
      retrospective electrocardiogram-gated spiral acquisition mode.
AB  - OBJECTIVE: To assess the image quality and effective radiation dose of
      prospectively electrocardiogram (ECG)-gated high-pitch spiral acquisition mode
      (flash mode) of dual-source CT (DSCT) coronary angiography (CTCA) in patients
      with high heart rates (HRs) as compared with retrospectively ECG-gated spiral
      acquisition mode. MATERIALS AND METHODS: Two hundred and sixty-eight consecutive
      patients (132 female, mean age: 55 +/- 11 years) with mean HR > 65 beats per
      minute (bpm) were prospectively included in this study. The patients were divided
      into two groups. Collection was performed in group A CTCA using flash mode
      setting at 20-30% of the R-R interval, and retrospectively ECG-gated spiral
      acquisition mode in group B. The image noise, contrast-to-noise ratio (CNR),
      image quality scores, effective radiation dose and influencing factors on image
      quality between the two groups were assessed. RESULTS: There were no significant
      differences in image quality scores and proportions of non-diagnostic coronary
      artery segments between two groups (image quality scores: 1.064 +/- 0.306 [group
      A] vs. 1.084 +/- 0.327 [group B], p = 0.063; proportion of non-diagnostic
      coronary artery segments: segment-based analysis 1.52% (group A) vs. 1.74% (group
      B), p = 0.345; patient-based analysis 7.5% (group A) vs. 6.7% (group B), p =
      0.812). The estimated radiation dose was 1.0 +/- 0.16 mSv in group A and 7.1 +/-
      1.05 mSv in group B (p = 0.001). CONCLUSION: In conclusion, in patients with HRs
      > 65 bpm without cardiac arrhythmia, the prospectively high-pitch spiral
      acquisition mode with image-acquired timing set at 20-30% of the R-R interval
      provides a similar image quality and low rate of non-diagnostic coronary segments
      to the retrospectively ECG-gated low-pitch spiral acquisition mode, with
      significant reduction of radiation exposure.

PMID- 23118567
TI  - CT-guided percutaneous transthoracic localization of pulmonary nodules prior to
      video-assisted thoracoscopic surgery using barium suspension.
AB  - OBJECTIVE: To describe our initial experience with CT-guided percutaneous barium
      marking for the localization of small pulmonary nodules prior to video-assisted
      thoracoscopic surgery (VATS). MATERIALS AND METHODS: From October 2010 to April
      2011, 10 consecutive patients (4 men and 6 women; mean age, 60 years) underwent
      CT-guided percutaneous barium marking for the localization of 10 small pulmonary
      nodules (mean size, 7.6 mm; range, 3-14 mm): 6 pure ground-glass nodules, 3 part
      solid nodules, and 1 solid nodule. A 140% barium sulfate suspension (mean amount,
      0.2 mL; range, 0.15-0.25 mL) was injected around the nodules with a 21-gauge
      needle. The technical details, surgical findings and pathologic features
      associated with barium localizations were evaluated. RESULTS: All nodules were
      marked within 3 mm (mean distance, 1.1 mm; range, 0-3 mm) from the barium ball
      (mean diameter, 9.6 mm; range, 8-16 mm) formed by the injected barium suspension.
      Pneumothorax occurred in two cases, for which one needed aspiration. However,
      there were no other complications. All barium balls were palpable during VATS and
      visible on intraoperative fluoroscopy, and were completely resected. Both the
      whitish barium balls and target nodules were identifiable in the frozen
      specimens. Pathology revealed one invasive adenocarcinoma, five adenocarcinoma-in
      situ, two atypical adenomatous hyperplasias, and two benign lesions. In all
      cases, there were acute inflammations around the barium balls which did not
      hamper the histological diagnosis of the nodules. CONCLUSION: CT-guided
      percutaneous barium marking can be an effective, convenient and safe pre
      operative localization procedure prior to VATS, enabling accurate resection and
      diagnosis of small or faint pulmonary nodules.

PMID- 23118568
TI  - Dual-energy CT in patients treated with anti-angiogenic agents for non-small cell
      lung cancer: new method of monitoring tumor response?
AB  - OBJECTIVE: To evaluate tumor responses in patients treated with anti-angiogenic
      agents for non-small cell lung cancer (NSCLC) by assessing intratumoral changes
      using a dual-energy CT (DECT) (based on Choi's criteria) and to compare it to
      traditional Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
      MATERIALS AND METHODS: Ten NSCLC patients treated with bevacizumab underwent
      DECT. Tumor responses to anti-angiogenic therapy were assessed and compared with
      the baseline CT results using both RECIST (size changes only) and Choi's criteria
      (reflecting net tumor enhancement). Kappa statistics was used to evaluate
      agreements between tumor responses assessed by RECIST and Choi's criteria.
      RESULTS: The weighted kappa value for the comparison of tumor responses between
      the RECIST and Choi's criteria was 0.72. Of 31 target lesions (21 solid nodules,
      8 lymph nodes, and two ground-glass opacity nodules [GGNs]), five lesions (16%)
      showed discordant responses between RECIST and Choi's criteria. Iodine-enhanced
      images allowed for a distinction between tumor enhancement and hemorrhagic
      response (detected in 14% [4 of 29, excluding GGNs] of target lesions on virtual
      nonenhanced images). CONCLUSION: DECT may serve as a useful tool for response
      evaluation after anti-angiogenic treatment in NSCLC patients by providing
      information on the net enhancement of target lesions without obtaining non
      enhanced images.

PMID- 23118569
TI  - Radiation dose reduction of chest CT with iterative reconstruction in image space
      - Part I: studies on image quality using dual source CT.
AB  - OBJECTIVE: To determine whether the image quality (IQ) is improved with iterative
      reconstruction in image space (IRIS), and whether IRIS can be used for radiation
      reduction in chest CT. MATERIALS AND METHODS: Standard dose chest CT (SDCT) in 50
      patients and low dose chest CT (LDCT) in another 50 patients were performed,
      using a dual-source CT, with 120 kVp and same reference mAs (50 mAs for SDCT and
      25 mAs for LDCT) employed to both tubes by modifying a dual-energy scan mode.
      Full-dose data were obtained by combining the data from both tubes and half-dose
      data were separated from a single tube. These were reconstructed by using a
      filtered back projection (FBP) and IRIS: full-dose FBP (F-FBP); full-dose IRIS (F
      IRIS); half-dose FBP (H-FBP) and half-dose IRIS (H-IRIS). Objective noise was
      measured. The subjective IQ was evaluated by radiologists for the followings:
      noise, contrast and sharpness of mediastinum and lung. RESULTS: Objective noise
      was significantly lower in H-IRIS than in F-FBP (p < 0.01). In both SDCT and
      LDCT, the IQ scores were highest in F-IRIS, followed by F-FBP, H-IRIS and H-FBP,
      except those for sharpness of mediastinum, which tended to be higher in FBP. When
      comparing CT images between the same dose and different reconstruction (F-IRIS/F
      FBP and H-IRIS/H-FBP) algorithms, scores tended to be higher in IRIS than in FBP,
      being more distinct in half-dose images. However, despite the use of IRIS, the
      scores were lower in H-IRIS than in F-FBP. CONCLUSION: IRIS generally helps
      improve the IQ, being more distinct at the reduced radiation. However, reduced
      radiation by half results in IQ decrease even when using IRIS in chest CT.

PMID- 23118570
TI  - Radiation dose reduction of chest CT with iterative reconstruction in image space
      - Part II: assessment of radiologists' preferences using dual source CT.
AB  - OBJECTIVE: To evaluate the impact of radiation dose and reconstruction algorithms
      on radiologists' preferences, and whether an iterative reconstruction in image
      space (IRIS) can be used for dose reduction in chest CT. MATERIALS AND METHODS:
      Standard dose chest CT (SDCT) in 50 patients and low dose chest CT (LDCT) in
      another 50 patients were performed, using a dual-source CT, with 120 kVp and same
      reference mAs (50 mAs for SDCT and 25 mAs for LDCT) employed to both tubes by
      modifying the dual-energy scan mode. Full-dose data were obtained by combining
      the data from both tubes and half-dose data were separated from one tube. These
      were reconstructed by using a filtered back projection (FBP) and IRIS: full-dose
      FBP (F-FBP); full-dose IRIS (F-IRIS); half-dose FBP (H-FBP) and half-dose IRIS (H
      IRIS). Ten H-IRIS/F-IRIS, 10 H-FBP/H-IRIS, 40 F-FBP/F-IRIS and 40 F-FBP/H-IRIS
      pairs of each SDCT and LDCT were randomized. The preference for clinical usage
      was determined by two radiologists with a 5-point-scale system for the
      followings: noise, contrast, and sharpness of mediastinum and lung. RESULTS:
      Radiologists preferred IRIS over FBP images in the same radiation dose for the
      evaluation of the lungs in both SDCT (p = 0.035) and LDCT (p < 0.001). When
      comparing between H-IRIS and F-IRIS, decreased radiation resulted in decreased
      preference. Observers preferred H-IRIS over F-FBP for the lungs in both SDCT and
      LDCT, even with reduced radiation dose by half in IRIS image (p < 0.05).
      CONCLUSION: Radiologists' preference may be influenced by both radiation dose and
      reconstruction algorithm. According to our preliminary results, dose reduction at
      50% with IRIS may be feasible for lung parenchymal evaluation.

PMID- 23118571
TI  - Hepatic cavernous hemangiomas: relationship between speed of intratumoral
      enhancement during dynamic MRI and apparent diffusion coefficient on diffusion
      weighted imaging.
AB  - OBJECTIVE: To investigate the relationships between the apparent diffusion
      coefficients (ADCs) on diffusion-weighted imaging (DWI) and the speed of contrast
      enhancement in hepatic hemangiomas. MATERIALS AND METHODS: Sixty-nine hepatic
      hemangiomas (>= 1 cm) were evaluated with DWI, by using multiple b values (b =
      50, 400, 800 s/mm(2)), followed by a gadolinium-enhanced dynamic MRI. The lesions
      were classified into three groups, according to the speed of contrast-enhancement
      on the portal phase. ADCs were measured on the ADC map automatically, and were
      calculated by using the two different b values (mADC(50-400) with b values = 50
      and 400; mADC(400-800) with b values = 400 and 800 s/mm(2)). RESULTS: The mean
      ADCs (* 10(-3) mm(2)/s) were significantly higher in the rapid group (1.9 +/-
      0.44) than in the intermediate (1.7 +/- 0.35, p = 0.046) or the slow groups (1.4
      +/- 0.34, p = 0.002). There were significant differences between the rapid and
      the slow groups in mADC(50-400) (2.12 vs. 1.48; p = 0.008) and mADC(400-800)
      (1.68 vs. 1.22, p = 0.010), and between the rapid and the intermediate groups in
      mADC(50-400) (2.12 vs. 1.79, p = 0.049). Comparing mADC(50-400) with mADC(400
      800), there was a significant difference only in the rapid group (p = 0.001).
      CONCLUSION: Higher ADCs of rapidly-enhancing hemangiomas may be related to richer
      intralesional vascular perfusion. Also, the restricted diffusion may be
      attributed to the difference of structural characteristics of hemangioma.

PMID- 23118572
TI  - Experimental evaluation of accelerated T1rho relaxation quantification in human
      liver using limited spin-lock times.
AB  - OBJECTIVE: It was reported lately that to obtain consistent liver T1rho
      measurement, at 3T MRI using six spin-lock times (SLTs), is feasible. In this
      study, the feasibility of using three or two SLT points to measure liver T1rho
      relaxation time was explored. MATERIALS AND METHODS: Seventeen healthy volunteers
      underwent 36 examinations. Three representative axial slices were selected to cut
      through the upper, middle, and lower liver. A rotary echo spin-lock pulse was
      implemented in a 2D fast field echo sequence. Spin-lock frequency was 500 Hz and
      the spin-lock times of 1, 10, 20, 30, 40, and 50 milliseconds (ms) were used for
      T1rho mapping. T1rho maps were constructed by using all 6 SLT points, three SLT
      points of 1, 20, and 50 ms, or two SLTs of 1 and 50 ms, respectively. Intra-class
      correlation coefficient (ICC) and Bland and Altman plot were used to assess the
      measurement agreement. RESULTS: Two examinations were excluded, due to motion
      artifact at the SLT of 50 ms. With the remaining 34 examinations, the ICC for 6
      SLT vs. 3-SLT T1rho measurements was 0.922, while the ICC for 6-SLT vs. 2-SLT
      T1rho measurement was 0.756. The Bland and Altman analysis showed a mean
      difference of 0.19 (95% limits of agreement: -1.34, 1.73) for 6-SLT vs. 3-SLT
      T1rho measurement, and the mean difference of 0.89 (95% limits of agreement: 
      1.67, 3.45) for 6-SLT vs. 2-SLT T1rho measurement. The scan re-scan
      reproducibility ICC (n = 11 subjects) was 0.755, 0.727, and 0.528 for 6-SLT
      measurement, 3-SLT measurement, and 2-SLT measurement, respectively. CONCLUSION:
      Adopting 3 SLTs of 1, 20, and 50 ms can be an acceptable alternative for the
      liver T1rho measurement, while 2 SLTs of 1 and 50 ms do not provide reliable
      measurement.

PMID- 23118573
TI  - Preliminary application of high-definition CT Gemstone Spectral Imaging in hand
      and foot tendons.
AB  - OBJECTIVE: To assess the feasibility of visualizing hand and foot tendon anatomy
      and disorders by Gemstone Spectral Imaging (GSI) high-definition CT (HDCT).
      MATERIALS AND METHODS: Thirty-five patients who suffered from hand or foot pain
      were scanned with GSI mode HDCT and MRI. Spectrum analysis was used to select the
      monochromatic images that provide the optimal contrast-to-noise ratio (CNR) for
      tendons. The image quality at the best selected monochromatic level and the
      conventional polychromatic images were compared. Tendon anatomy and disease were
      also analyzed at GSI and MRI. RESULTS: The monochromatic images at about 65 keV
      (mean 65.09 +/- 2.98) provided the optimal CNR for hand and foot tendons. The
      image quality at the optimal selected monochromatic level was superior to
      conventional polychromatic images (p = 0.005, p < 0.05). GSI was useful in
      visualizing hand and foot tendon anatomy and disorders. There were no statistical
      differences between GSI and MRI with regard to tendon thickening (chi(2) = 0, p >
      0.05), compression (chi(2) = 0.5, p > 0.05), absence (chi(2) = 0, p > 0.05) and
      rupture (chi(2) = 0, p > 0.05). GSI was significantly less sensitive than MRI in
      displaying tendon adhesion (chi(2) = 4.17, p < 0.05), degeneration (chi(2) =
      4.17, p < 0.05), and tendinous sheath disease (chi(2) = 10.08, p < 0.05).
      CONCLUSION: GSI with monochromatic images at 65 keV displays clearly the most
      hand and foot tendon anatomy and disorders with image quality improved, as
      compared with conventional polychromatic images. It may be used solely or
      combined with MRI in clinical work, depending on individual patient disease
      condition.

PMID- 23118574
TI  - Prognostic value of volume-based (18)F-fluorodeoxyglucose PET/CT parameters in
      patients with clinically node-negative oral tongue squamous cell carcinoma.
AB  - OBJECTIVE: To evaluate the prognostic value of volume-based metabolic parameters
      measured with (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography
      (PET) in patients with clinically node-negative (cN0) oral tongue squamous cell
      carcinoma (OTSCC) as compared with other prognostic factors. MATERIALS AND
      METHODS: In this study, we included a total of 57 patients who had been diagnosed
      with cN0 tongue cancer by radiologic, (18)F-FDG PET/CT, and physical
      examinations. The maximum standardized uptake value (SUV(max)), average SUV
      (SUV(avg)), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for
      primary tumors were measured with (18)F-FDG PET. The prognostic significances of
      these parameters and other clinical variables were assessed by Cox proportional
      hazards regression analysis. RESULTS: In the univariate analysis, pathological
      node (pN) stage, American Joint Committee on Cancer (AJCC) stage, SUV(max),
      SUV(avg), MTV, and TLG were significant predictors for survival. On a
      multivariate analysis, pN stage (hazard ratio = 10.555, p = 0.049), AJCC stage
      (hazard ratio = 13.220, p = 0.045), and MTV (hazard ratio = 2.698, p = 0.033)
      were significant prognostic factors in cN0 OTSCC patients. The patients with MTV
      >= 7.78 cm(3) showed a worse prognosis than those with MTV < 7.78 cm(3) (p =
      0.037). CONCLUSION: The MTV of primary tumor as a volumetric parameter of (18)F
      FDG PET, in addition to pN stage and AJCC stage, is an independent prognostic
      factor for survival in cN0 OTSCC.

PMID- 23118575
TI  - Opportunities for 2-[(18)F] fluoro-2-deoxy-D-glucose PET/CT in cervical-vaginal
      neuroendocrine carcinoma: case series and literature review.
AB  - OBJECTIVE: Neuroendocrine cervical carcinoma is a rare subtype of cervical
      cancer. These tumors exhibit an aggressive behavior with early regional lymph
      node and distant metastases. The purpose of our study was to describe five cases
      of neuroendocrine cervical-vaginal carcinoma and to discuss the potential of the
      2-[(18)F] fluoro-2-deoxy-D-glucose positron emission tomography/computed
      tomography ((18)F-FDG PET/CT) scan for the detection of this rare malignancy.
      MATERIALS AND METHODS: Five cases of cervical-vaginal neuroendocrine tumor were
      retrospectively collected, during a two year (from September 2009 to August 2011)
      period in our hospital. The clinical staging distributions were International
      Federation of Gynecology and Obstetrics (FIGO) stage IB2 (1 of 5), stage IIA (3
      of 5) and stage IVA (1 of 5). RESULTS: Two cases (cases 1 and 4) were restaged
      after (18)F-FDG PET/CT scan in the initial staging process. Post-treatment (18)F
      FDG PET/CT scans, in three patients, revealed positive findings for tumor
      recurrence or lymph node metastases. Two patients (cases 2 and 3) died of tumor
      within two years. CONCLUSION: (18)F-FDG PET/CT scan is a useful tool in cervical
      vaginal neuroendocrine tumor. In its initial staging, the (18)F-FDG PET/CT scan
      may help assess the possible nodal involvement or early hematogeneous spreading.
      We can also use the (18)F-FDG PET/CT to detect local recurrence and to evaluate
      the treatment response after clinical manipulation.

PMID- 23118576
TI  - Trends of CT use in the pediatric emergency department in a tertiary academic
      hospital of Korea during 2001-2010.
AB  - OBJECTIVE: We wanted to assess the trends of computed tomography (CT)
      examinations in a pediatric emergency department (ED). MATERIALS AND METHODS: We
      searched the medical database to identify the pediatric patients who had visited
      the ED, and the number of CTs conducted from January 2001 to December 2010. We
      analyzed the types of CTs, according to the anatomic region, and the patients who
      underwent CT examinations for multiple regions. Data were stratified, according
      to the patient age (< 13 years and 13 <= ages < 18 years). RESULTS: The number of
      CTs performed per 1000 patients increased by 92% during the 10-year period (per
      1000 patients, increased from 50.1 CTs in 2001 to 156.5 CTs in 2006, and then
      decreased to 96.0 CTs in 2010). Although head CTs were performed most often
      (74.6% of all CTs), facial bone CTs showed the largest rate of increase (3188%)
      per 1000 patients, followed by cervical CTs (642%), abdominal CTs (474%),
      miscellaneous CTs (236%), chest CTs (89%) and head CTs (39%). The number of
      patients who had CT examinations for multiple regions in the same day showed a
      similar pattern of increase, to that of overall CT examinations. Increase of CT
      utilization was more pronounced in adolescents than in pediatric patients younger
      than 13 years (189% vs. 59%). CONCLUSION: The utilization of CTs increases from
      2001 to 2006, and has declined since 2006. The increase of CTs is more pronounced
      in adolescents, and facial bone CTs prevail in increased number of examination
      followed by cervical CTs, abdominal CTs, miscellaneous CTs, chest CTs, and head
      CTs.

PMID- 23118577
TI  - Which phantom is better for assessing the image quality in full-field digital
      mammography?: American College of Radiology Accreditation phantom versus digital
      mammography accreditation phantom.
AB  - OBJECTIVE: To compare between the American College of Radiology (ACR)
      accreditation phantom and digital mammography accreditation phantom in assessing
      the image quality in full-field digital mammography (FFDM). MATERIALS AND
      METHODS: In each week throughout the 42-week study, we obtained phantom images
      using both the ACR accreditation phantom and the digital mammography
      accreditation phantom, and a total of 42 pairs of images were included in this
      study. We assessed the signal-to-noise ratio (SNR) in each phantom image. A
      radiologist drew a square-shaped region of interest on the phantom and then the
      mean value of the SNR and the standard deviation were automatically provided on a
      monitor. SNR was calculated by an equation, measured mean value of SNR-constant
      coefficient of FFDM/standard deviation. Two breast radiologists scored visible
      objects (fibers, specks, and masses) with soft-copy images and calculated the
      visible rate (number of visible objects/total number of objects). We compared SNR
      and the visible rate of objects between the two phantoms and calculated the k
      coefficient for interobserver agreement. RESULTS: The SNR of the ACR
      accreditation phantom ranged from 42.0 to 52.9 (Mean, 47.3 +/- 2.79) and that of
      Digital Phantom ranged from 24.8 to 54.0 (Mean, 44.1 +/- 9.93) (p = 0.028). The
      visible rates of all three types of objects were much higher in the ACR
      accreditation phantom than those in the digital mammography accreditation phantom
      (p < 0.05). Interobserver agreement for visible rates of objects on phantom
      images was fair to moderate agreement (k-coefficients: 0.34-0.57). CONCLUSION:
      The ACR accreditation phantom is superior to the digital mammography
      accreditation phantom in terms of SNR and visibility of phantom objects. Thus,
      ACR accreditation phantom appears to be satisfactory for assessing the image
      quality in FFDM.

PMID- 23118578
TI  - Radiofrequency ablation for viable hepatocellular carcinoma around retained
      iodized oil after transcatheter arterial chemoembolization: usefulness of biplane
      fluoroscopy plus ultrasound guidance.
AB  - OBJECTIVE: To assess the technical feasibility and local efficacy of biplane
      fluoroscopy plus US-guided percutaneous radiofrequency ablation (RFA) for viable
      hepatocellular carcinoma (HCC) around retained iodized oil after transcatheter
      arterial chemoembolization (TACE). MATERIALS AND METHODS: Our prospective study
      was approved by our institutional review board and informed consent was obtained
      from all participating patients. For patients with viable HCC around retained
      iodized oil after TACE, biplane fluoroscopy plus US-guided RFA was performed. We
      evaluated the rate of technical success and major complications on a post-RFA CT
      examination and local tumor progression with a follow-up CT. RESULTS: Among 40
      consecutive patients, 19 were excluded due to one of the following reasons:
      poorly visible HCC on fluoroscopy (n = 13), high risk location (n = 2), RFA
      performed under monoplane fluoroscopy and US guidance (n = 2), and poorly
      identifiable new HCCs on US (n = 2). The remaining 21 patients with 21 viable
      HCCs were included. The size of total tumors ranged from 1.4 to 5.0 cm (mean: 3.2
      cm) in the longest diameter. Technical success was achieved for all 21 HCCs, and
      major complications were observed in none of the patients. During the follow-up
      period (mean, 20.3 months; range, 6.5-29.9 months), local tumor progression was
      found in two patients (2/21, 9.5%). Distant intrahepatic metastasis developed in
      76.2% (16/21) of patients. CONCLUSION: When retained iodized oil around the tumor
      after TACE hampers the targeting of the viable tumor for RFA, biplane fluoroscopy
      plus US-guided RFA may be performed owing to its technical feasibility and
      effective treatment for viable HCCs.

PMID- 23118579
TI  - Percutaneous biliary drainage using open cell stents for malignant biliary hilar
      obstruction.
AB  - OBJECTIVE: To evaluate the feasibility, safety and the effectiveness of the
      complex assembly of open cell nitinol stents for biliary hilar malignancy.
      MATERIALS AND METHODS: During the 10 month period between January and October
      2007, 26 consecutive patients with malignant biliary hilar obstruction underwent
      percutaneous insertion of open cell design nitinol stents. Four types of stent
      placement methods were used according to the patients' ductal anatomy of the
      hilum. We evaluated the technical feasibility of stent placement, complications,
      patient survival, and the duration of stent patency. RESULTS: Bilobar biliary
      stent placement was conducted in 26 patients with malignant biliary obstruction-T
      (n = 9), Y (n = 7), crisscross (n = 6) and multiple intersecting types (n = 4).
      Primary technical success was obtained in 24 of 26 (93%) patients. The crushing
      of the 1st stent during insertion of the 2nd stent occurred in two cases. Major
      complications occurred in 2 of 26 patients (7.7%). One case of active bleeding
      from hepatic segmental artery and one case of sepsis after procedure occurred.
      Clinical success was achieved in 21 of 24 (87.5%) patients, who were followed for
      a mean of 141.5 days (range 25-354 days). The mean primary stent patency period
      was 191.8 days and the mean patient survival period was 299 days. CONCLUSION:
      Applying an open cell stent in the biliary system is feasible, and can be
      effective, especially in multiple intersecting stent insertions in the hepatic
      hilum.

PMID- 23118580
TI  - Immunoglobulin G4-related sclerosing disease involving the urethra: case report.
AB  - Immunoglobulin G4 (IgG4)-related sclerosing disease is a systemic disease
      characterized by extensive IgG4-positive plasma cells and T-lymphocyte
      infiltration in various organs. We described the imaging findings of an IgG4
      related inflammatory pseudotumor in the urethra. The urethral mass showed
      isoattenuation on unenhanced CT images, delayed enhancement on enhanced CT
      images, iso- to slight hyper-intensity on T1 and T2 weighted magnetic resonance
      images, diffusion restriction on diffusion weighted images, and heterogeneously
      low echogeneity on ultrasonography.

PMID- 23118581
TI  - Uremic encephalopathy with atypical magnetic resonance features on diffusion
      weighted images.
AB  - Uremic encephalopathy is a well-known disease with typical MR findings including
      bilateral vasogenic or cytotoxic edema at the cerebral cortex or basal ganglia.
      Involvement of the basal ganglia has been very rarely reported, typically
      occurring in uremic-diabetic patients. We recently treated a patient who had non
      diabetic uremic encephalopathy with an atypical lesion distribution involving the
      supratentorial white matter, without cortical or basal ganglia involvement. To
      the best of our knowledge, this is only the second reported case of non-diabetic
      uremic encephalopathy with atypical MR findings.

PMID- 23118582
TI  - Imaging finding of malignant melanoma of Eustachian tube with extension to middle
      ear cavity: case report.
AB  - We report a case of malignant melanoma of Eustachian tube with extension to the
      middle ear cavity and nasopharynx in a 51-year-old woman who presented with right
      ear fullness. Computed tomography showed a soft tissue mass in the middle ear
      cavity and caused the widening and eroding of the bony eustachian tube. Magnetic
      resonance imaging showed well enhancing mass in eustachian tube extending
      nasopharynx to middle ear cavity. A biopsy of the middle ear cavity mass revealed
      a malignant amelanotic melanoma.

PMID- 23118583
TI  - Hemodynamic change in pulmonary vein stenosis after radiofrequency ablation:
      assessment with magnetic resonance angiography.
AB  - We present a case of pulmonary vein (PV) stenosis after radio-frequency (RF)
      ablation, in which a hemodynamic change in the pulmonary artery was similar to
      that of congenital PV atresia on time-resolved contrast-enhanced magnetic
      resonance angiography (TR-MRA). A 48-year-old man underwent RF ablation due to
      atrial fibrillation. The patient subsequently complained of hemoptysis, dyspnea
      on exertion, and right chest pain. Right PV stenosis after catheter ablation was
      diagnosed through chest computed tomography and lung perfusion scan. Pulmonary TR
      MRA revealed the pulmonary artery via systemic arterial collaterals and draining
      systemic collateral veins. On a velocity-encoded cine image, the flow direction
      of the right pulmonary artery was reversed in the diastolic phase and the left
      pulmonary artery demonstrated continuous forward flow throughout the cardiac
      cycle. These hemodynamic changes were similar to those seen in congenital
      unilateral PV atresia.

PMID- 23118584
TI  - Shear-wave elastography of segmental infarction of the testis.
AB  - Segmental testicular infarction (STI) is a rare cause of acute scrotum. The
      spectrum of findings on gray-scale and color Doppler ultrasonography differ
      depending on the time between the onset of testicular pain and the
      ultrasonography examination. We are not aware of the usefulness of shear-wave
      elastography for the diagnosis of STI. We report the shear-wave elastography
      features in a case of STI and discuss the role of this diagnostic modality in the
      differential diagnosis.

PMID- 23118585
TI  - Primary malignant melanoma of the mediastinum: radiologic and pathologic
      correlation in two case.
AB  - Primary malignant melanoma of the anterior mediastinum is extremely rare,
      accounting for 0.1-0.5% of all primary malignant neoplasms. These tumors may be
      mistakenly diagnosed as lymphomas, thymic carcinomas and malignant germ-cell
      tumors of the mediastinum. We describe two cases of primary malignant melanomas
      of the anterior mediastinum and report their CT and pathology findings.

PMID- 23118586
TI  - Intrahepatic portosystemic venous shunt: successful embolization using the
      Amplatzer Vascular Plug II.
AB  - A 67-year-old woman presented with memory impairment and behavioral changes.
      Brain MRI indicated hepatic encephalopathy. Abdominal CT scans revealed an
      intrahepatic portosystemic venous shunt that consisted of two shunt tracts to the
      aneurysmal sac that communicated directly with the right hepatic vein. The large
      tract was successfully occluded by embolization using the newly available
      AMPLATZERTM Vascular Plug II and the small tract was occluded by using coils. The
      patient's symptoms disappeared after shunt closure and she remained free of
      recurrence at the 3-month follow-up evaluation.

PMID- 23118587
TI  - Toxicity of lead: A review with recent updates.
AB  - Lead poisoning has been recognized as a major public health risk, particularly in
      developing countries. Though various occupational and public health measures have
      been undertaken in order to control lead exposure, cases of lead poisoning are
      still reported. Exposure to lead produces various deleterious effects on the
      hematopoietic, renal, reproductive and central nervous system, mainly through
      increased oxidative stress. These alterations play a prominent role in disease
      manifestations. Modulation of cellular thiols for protection against reactive
      oxygen species (ROS) has been used as a therapeutic strategy against lead
      poisoning. N-acetylcysteine, alpha-lipoic acid, vitamin E, quercetin and a few
      herbal extracts show prophylaxis against the majority of lead mediated injury in
      both in vitro and in vivo studies. This review provides a comprehensive account
      of recent updates describing health effects of lead exposure, relevant biomarkers
      and mechanisms involved in lead toxicity. It also updates the readers about
      recent advances in chelation therapy and newer therapeutic strategies, like
      nanoencapsulation, to treat lead induced toxic manifestations.

PMID- 23118588
TI  - Decreased activity and accelerated apoptosis of neutrophils in the presence of
      natural polyphenols.
AB  - Prolonged or excessive formation and liberation of cytotoxic substances from
      neutrophils intensifies inflammation and the risk of tissue damage. From this
      perspective, administration of substances which are able to reduce activity of
      neutrophils and to enhance apoptosis of these cells may improve the therapy of
      pathological states connected with persistent inflammation. In this short review,
      neutrophil oxidative burst and apoptosis are presented as potential targets for
      pharmacological intervention. Effects of natural polyphenols (resveratrol,
      pterostilbene, pinosylvin, piceatannol, curcumin, N-feruloylserotonin) are
      summarised, considering the ability of these compounds to affect inflammation and
      particularly neutrophil activity. The intended neutrophil inhibition is
      introduced as a part of a new strategy for pharmacological modulation of chronic
      inflammatory processes, focused on supporting innate anti-inflammatory mechanisms
      and enhancing resolution of inflammation.

PMID- 23118589
TI  - Polyphenol derivatives - potential regulators of neutrophil activity.
AB  - The study provides new information on the effect of natural polyphenols
      (derivatives of stilbene - resveratrol, pterostilbene, pinosylvin and piceatannol
      and derivatives of ferulic acid - curcumin, N-feruloylserotonin) on the activity
      of human neutrophils in influencing oxidative burst. All the polyphenols tested
      were found to reduce markedly the production of reactive oxygen species released
      by human neutrophils on extra-and intracellular levels as well as in cell free
      system. Moreover, pinosylvin, curcumin, N-feruloylserotonin and resveratrol
      decreased protein kinase C activity involved in neutrophil signalling and
      reactive oxygen species production. Our results suggest that due to their anti
      neutrophil activity, the polyphenols tested might be attractive candidates in
      therapeutic development.

PMID- 23118590
TI  - Effect of stilbene derivative on superoxide generation and enzyme release from
      human neutrophils in vitro.
AB  - Neutrophils represent the body's primary line of defense against invading
      pathogens. They most rapidly reach the site of injury or infection, liberate
      antimicrobial proteins, proteases and produce reactive oxygen species. Prolonged
      or excessive liberation of these very effective and toxic substances could
      intensify the inflammatory process and enhance tissue damage in many diseases,
      such as allergies, infections and rheumatoid arthritis. Pterostilbene belongs to
      stilbenoids, structural analogues of resveratrol, which act as natural protective
      agents in defending the plant against viral and microbial attack. It possesses
      anticancerous, antidiabetic and anti-inflammatory properties.The study provides
      new information on the effect of pterostilbene [0.01-100 umol/l] on superoxide
      generation in and myeloperoxidase (MPO) release from azurophil granules of
      isolated human neutrophils. PMA [1umol/l], which activates NADPH-oxidase via
      protein kinase C, was used for stimulation of neutrophils Unstimulated cells
      showed neither superoxide generation nor myelopereoxidase release after
      preincubation with the drug studied. Pterostilbene dose dependently decreased
      superoxide generation in and MPO release from stimulated human neutrophils,
      however a significant decrease was recorded only in the concentration 100 umol/l.
      The effect of pterostilbene was more pronounced on superoxide generation in
      comparison to MPO release. Our results suggest that the effect of pterostilbene
      may prove beneficial in controlling inflammation.

PMID- 23118591
TI  - Involvement of caspase-3 in stilbene derivatives induced apoptosis of human
      neutrophils in vitro.
AB  - Chronic inflammatory diseases, e.g. rheumatoid arthritis or cystic fibrosis, are
      characterised by neutrophil infiltration in inflamed tissues. Dysregulated
      neutrophil death may contribute to the pathogenesis of diseases where neutrophils
      play a role. Stilbene derivatives are reported to activate apoptosis in different
      cell lines. Neutrophils from healthy volunteers were incubated in vitro with
      resveratrol, pterostilbene, pinosylvin or piceatannol (1-100 umol/l), and
      cytotoxicity and apoptosis were measured by luminometry and flow cytometry,
      respectively. Enhancement and/or inhibition of human recombinant caspase-3 enzyme
      activity were measured by luminometry. None of the stilbene derivatives tested
      increased ATP liberation from human neutrophils, thus showing no direct
      cytotoxicity effect. Resveratrol and piceatannol (100 umol/l) treated neutrophils
      had a higher rate of apoptosis compared to non-treated cells. Pterostilbene and
      pinosylvin (1 umol/l), yet not resveratrol or piceatannol, increased the activity
      of caspase-3. However in the concentration of 100 umol/l, all stilbene
      derivatives tested inhibited caspase-3 activity. Their effects on human
      neutrophil apoptosis differed according to the structure of the molecule.
      Additional studies are required to get insight into the mechanisms involved in
      the effects of the substances tested on neutrophil viability.

PMID- 23118592
TI  - Quercetin inhibits degranulation and superoxide generation in PMA stimulated
      neutrophils.
AB  - Activated neutrophils represent the main source of myeloperoxidase (MPO),
      superoxide (SO) and subsequently derived oxygen metabolites. They have important
      microbicidal activities, however in inflammatory conditions they may secondarily
      attack surrounding tissues. Overproduction of reactive oxygen species, prolonged
      or excessive liberation of MPO and other effective yet also toxic substances from
      neutrophils may participate in disturbed apoptosis, intensify the inflammatory
      processes and result in serious human diseases. The inhibitory effect of
      quercetin on PMA stimulated SO generation in isolated human neutrophils was found
      to be dose-dependent, without affecting the activity of intact isolated
      neutrophils. At comparable conditions, quercetin was more potent in inhibiting
      MPO release than SO generation. Our results indicate that quercetin could support
      resolution of inflammation through decreased activity of neutrophils, i.e.
      respiratory burst and degranulation.

PMID- 23118593
TI  - Pharmacological influence on processes of adjuvant arthritis: Effect of the
      combination of an antioxidant active substance with methotrexate.
AB  - Oxygen metabolism has an important role in the pathogenesis of rheumatoid
      arthritis. A certain correlation was observed between oxidative stress, arthritis
      and the immune system. Reactive oxygen species produced in the course of cellular
      oxidative phosphorylation and by activated phagocytic cells during oxidative
      burst, exceed the physiological buffering capacity and result in oxidative
      stress. The excessive production of ROS can damage protein, lipids, nucleic
      acids, and matrix components. Patients with rheumatoid arthritis have an altered
      antioxidant defense capacity barrier. In the present study the effect of
      substances with antioxidative properties, i.e. pinosylvin and carnosine, was
      determined in monotherapy for the treatment of adjuvant arthritis (AA). Moreover
      carnosine was evaluated in combination therapy with methotrexate. Rats with AA
      were administered first pinosylvin (30 mg/kg body mass daily per os), second
      carnosine (150 mg/kg body mass daily per os) in monotherapy for a period of 28
      days. Further, rats with AA were administered methotrexate (0.3 mg/kg body mass 2
      times weekly per os), and a combination of methotrexate+carnosine, with the
      carnosine dose being the same as in the previous experiment. Parameters, i.e.
      changes in hind paw volume and arthritic score were determined in rats as
      indicators of destructive arthritis-associated clinical changes. Plasmatic levels
      of TBARS and lag time of Fe(2+)-induced lipid peroxidation (tau-FeLP) in plasma
      and brain were specified as markers of oxidation. Plasmatic level of CRP and
      activity of gamma-glutamyltransferase (GGT) in spleen and joint were used as
      inflammation markers. In comparison to pinosylvin, administration of carnosine
      monotherapy led to a significant decrease in the majority of the parameters
      studied. In the combination treatment with methotrexate+carnosine most parameters
      monitored were improved more remarkably than by methotrexate alone. Carnosine can
      increase the disease-modifying effect of methotrexate treatment in rat AA.

PMID- 23118594
TI  - Effect of prenatal administration of venlafaxine on postnatal development of rat
      offspring.
AB  - About 3% of pregnant women are treated with antidepressant drugs during
      gestation. After delivery the number of treated women increases to 5 to 7%. Most
      prescribed antidepressants in pregnancy are selective serotonin re-uptake
      inhibitors and/or serotonin and noradrenaline re-uptake inhibitors, such as
      fluoxetine, paroxetine, sertraline, citalopram and venlafaxine (VENF). Despite
      the fact that VENF has been assigned to pregnancy category C by the FDA,
      experimental studies with this drug are rare. The aim of this pilot study was to
      investigate the effect of prenatal administration of VENF on early postnatal
      development of rat offspring and selected biochemical variables at weaning of
      pups. Pregnant female Wistar rats were treated with VENF from day 15 to 20 of
      gestation at the doses of 7.5, 37.5 and 70 mg/kg. Females were allowed to
      spontaneously deliver their pups. After delivery the pups were inspected for
      viability, gross malformation and they were weighed on day 0, 4 and 21 post
      partum. On day 21 post partum, the pups were killed, brains were removed from the
      skulls and blood samples were collected for biochemical assay (proteins, glucose
      GOD, glucose-HEX, lactate dehydrogenase, aspartate aminotransferase, alanine
      aminotransferase and total antioxidant status). The study showed that prenatal
      VENF administration resulted in a mild maternal intoxication manifested by
      decreased body weight gain of pregnant females. There was no effect of the drug
      tested on the body and brain weights of offspring. No obvious morphological
      alterations were observed in the delivered pups. Similarly, there were no changes
      in the selected biochemical variables determined.

PMID- 23118595
TI  - Review of skin irritation/corrosion Hazards on the basis of human data: A
      regulatory perspective.
AB  - Regulatory classification of skin irritation has historically been based on
      rabbit data, however current toxicology processes are transitioning to in vitro
      alternatives. The in vitro assays have to provide sufficient level of sensitivity
      as well as specificity to be accepted as replacement methods for the existing in
      vivo assays. This is usually achieved by comparing the in vitro results to
      classifications obtained in animals. Significant drawback of this approach is
      that neither in vivo nor in vitro methods are calibrated against human hazard
      data and results obtained in these assays may not correspond to situation in
      human.The main objective of this review was to establish an extended database of
      substances classified according to their human hazard to serve for further
      development of alternative methods relevant to human health as well as resource
      for improved regulatory classification. The literature has been reviewed to
      assemble all the available information on the testing of substances in the human
      4 h human patch test, which is the only standardized protocol in humans matching
      the exposure conditions of the regulatory accepted in vivo rabbit skin irritation
      test.A total of 81 substances tested according to the defined 4 h human patch
      test protocol were found and collated into a dataset together with their existing
      in vivo classifications published in the literature. While about 50% of the
      substances in the database are classified as irritating based on the rabbit skin
      test, on using the 4 h HPT test, less than 20% were identified as acutely
      irritant to human skin. Based on the presented data, it can be concluded that the
      rabbit skin irritation test largely over-predicts human responses for the
      evaluated chemicals. Correct classification of the acute skin irritation hazard
      will only be possible if newly developed in vitro toxicology methods will be
      calibrated to produce results relevant to man.

PMID- 23118596
TI  - Some linguistic and pragmatic considerations affecting science reporting in
      English by non-native speakers of the language.
AB  - Approximately 50% of publications in English peer reviewed journals are
      contributed by non-native speakers (NNS) of the language. Basic thought processes
      are considered to be universal yet there are differences in thought patterns and
      particularly in discourse management of writers with different linguistic and
      cultural backgrounds. The study highlights some areas of potential
      incompatibility in native and NNS processing of English scientific papers.
      Principles and conventions in generating academic discourse are considered in
      terms of frequently occurring failures of NNS to meet expectations of editors,
      reviewers, and readers. Major problem areas concern organization and flow of
      information, principles of cohesion and clarity, cultural constraints, especially
      those of politeness and negotiability of ideas, and the complicated area of
      English modality pragmatics. The aim of the paper is to sensitize NN authors of
      English academic reports to problem areas of discourse processing which are
      stumbling blocks, often affecting acceptance of manuscripts. The problems
      discussed are essential for acquiring pragmalinguistic and sociocultural
      competence in producing effective communication.

PMID- 23118597
TI  - Learning Through Silence: Amping up Cognition After Neonatal Hypoxic Seizures
      Through AMPA Receptor Inhibition.

PMID- 23118598
TI  - "Please release me, let me go"-changes in presynaptic release following status
      epilepticus.

PMID- 23118599
TI  - A scaffold as a platform for new therapies?

PMID- 23118600
TI  - Tumors generate excitement: the role of glutamate in tumor-related epilepsy.

PMID- 23118601
TI  - Dyeing to be fired: firing order distinguishes two types of bursting activity.

PMID- 23118602
TI  - "Untangling" Alzheimer's disease and epilepsy.
AB  - There is a substantial body of evidence that spontaneous recurrent seizures occur
      in a subset of patients with Alzheimer disease (AD), especially the familial
      forms that have an early onset. In transgenic mice that simulate these genetic
      forms of AD, seizures or reduced seizure threshold have also been reported.
      Mechanisms underlying the seizures or reduced seizure threshold in these mice are
      not yet clear and are likely to be complex, because the synthesis of amyloid beta
      (Abeta) involves many peptides and proteases that influence excitability. Based
      on transgenic mouse models of AD where Abeta and its precursor are elevated, it
      has been suggested that seizures are caused by the downregulation of the Nav1.1
      sodium channel in a subset of GABAergic interneurons, leading to a reduction in
      GABAergic inhibition. Another mechanism of hyperexcitability appears to involve
      tau, because deletion of tau reduces seizures in some of the same transgenic
      mouse models of AD. Therefore, altered excitability may be as much a
      characteristic of AD as plaques and tangles-especially for the familial forms of
      AD.

PMID- 23118603
TI  - Seizures in Alzheimer disease: clinical and epidemiological data.
AB  - Alzheimer disease (AD) and epilepsy are disorders commonly seen in the elderly.
      Many studies have shown that patients with AD are at increased risk for
      developing seizures and epilepsy. Whereas, patients with specific types of
      epilepsy, such as temporal lobe epilepsy (TLE), experience some degree of
      cognitive dysfunction, questions have been raised as to whether these disorders
      share some underlying pathophysiologic mechanisms or whether one is an
      epiphenomenon of the other. In this report, we review some of the available
      clinical and epidemiologic literature on various aspects of the topic of seizures
      in AD, including seizure rates and types, risk factors for seizures,
      electroencephalographic findings, treatment options, limitations, and
      methodological issues. Overall, multiple aspects of the literature on seizures
      and epilepsy in AD, including diagnosis, risk factors, the role of EEG in
      diagnosis, and the response to treatment are not clear and suffer from many
      methodological limitations and gaps.

PMID- 23118604
TI  - Neurostimulation-past, present, and beyond.
AB  - Neurostimulation as a treatment for epilepsy has been around for almost 20 years
      in the form of vagus nerve stimulation. Newer types of neurostimulation are being
      developed and stand on the brink of approval for use. The two newest therapies,
      not yet approved in the United States, are deep brain stimulation and the
      Responsive Neurostimulator System . In fact, in Europe, approval has already been
      given for deep brain stimulation and newer forms of vagus nerve stimulation.
      Efficacy is similar between these therapies, and side effects are moderate, so
      what will be the future? The challenge will be to learn how to use these
      therapies correctly and offer the right treatment for the right patient.

PMID- 23118605
TI  - The relationship between nocturnal discharges and language dysfunction in
      rolandic epilepsy: treat the child, not the adage.

PMID- 23118606
TI  - Epilepsy surgery: a broken bridge between utility and utilization.

PMID- 23118607
TI  - The Kids Aren't All Right.

PMID- 23118608
TI  - Targeting anti-epileptic drug therapy without collateral damage: nanocarrier
      based drug delivery.

PMID- 23118609
TI  - Psychopathology and epilepsy: a two-way relationship.

PMID- 23118610
TI  - Cortico-thalamic connections and temporal lobe epilepsy: an evolving story.

PMID- 23118611
TI  - The evaluation of thyroid diseases in patients with pemphigus vulgaris.
AB  - BACKGROUND: Thyroid disorders may affect all of the organ systems of the body and
      they are also highly associated with a wide variety of skin disorders. The aim of
      this study was to investigate the prevalence of thyroid function abnormalities
      and thyroid autoimmunity in patients with pemphigus vulgaris (PV) and to
      determine the association between thyroid disorders and clinical involvement and
      systemic corticosteroid treatment in patients with PV. METHODS: The study
      consisted of eighty patients with PV and eighty healthy individuals. Thyroid
      functions (fT3, fT4, and TSH) and thyroid autoimmunity (anti-thyroid peroxidase
      (anti-TPO), and anti-thyroglobulin (anti-Tg) antibodies) were investigated in
      both groups. Primary thyroid disease (PTD) was diagnosed with one or more of the
      following diagnostic criteria: (i) positive antithyroid antibodies, (ii) primary
      thyroid function abnormalities. RESULTS: Significant changes in the serum thyroid
      profile were found in 16% (13/80) of the PV group and 5% (4/80) of the control
      group. Positive titers of antithyroid antibodies (anti-TPO and anti-Tg) were
      observed in 7 patients (9%) with PV and one in the control group (1,2%).
      Hashimoto thyroiditis was diagnosed in 9% of PV patients and it was found to be
      more prevalent in the mucosal form of PV. PTD was found in 13 of (%16) PV
      patients which was significantly high compared to controls. PTD was not found to
      be associated with systemic corticosteroid use. Free T3 levels were significantly
      lower in PV group compared to the control group and free T4 levels were
      significantly higher in PV group compared to the controls. CONCLUSIONS: PV may
      exist together with autoimmune thyroid diseases especially Hashimoto thyroiditis
      and primer thyroid diseases. Laboratory work-up for thyroid function tests and
      thyroid autoantibodies should be performed to determine underlying thyroid
      diseases in patients with PV.

PMID- 23118612
TI  - Distributions, sources, and backward trajectories of atmospheric polycyclic
      aromatic hydrocarbons at Lake Small Baiyangdian, Northern China.
AB  - Air samples were collected seasonally at Lake Small Baiyangdian, a shallow lake
      in northern China, between October 2007 and September 2008. Gas phase,
      particulate phase and dust fall concentrations of polycyclic aromatic
      hydrocarbons (PAHs) were measured using a gas chromatograph-mass spectrometer (GC
      MS). The distribution and partitioning of atmospheric PAHs were studied, and the
      major sources were identified; the backward trajectories of air masses starting
      from the center of Lake Small Baiyangdian were calculated for the entire year.
      The following results were obtained: (1) The total concentration of 16 priority
      controlled PAHs (PAH16) in the gas phase was 417.2 +/- 299.8 ng . m(-3), in the
      particulate phase was 150.9 +/- 99.2 ng . m(-3), and in dust fall was 6930.2 +/-
      3206.5 ng . g(-1). (2) Vehicle emission, coal combustion, and biomass combustion
      were the major sources in the Small Baiyangdian atmosphere and accounted for
      28.9%, 45.1% and 26.0% of the total PAHs, respectively. (3) Winter was dominated
      by relatively greater PAHs polluted northwesterly air mass pathways. Summer
      showed a dominant relatively clean southern pathway, whereas the trajectories in
      autumn and spring might be associated with high pollution from Shanxi or Henan
      province.

PMID- 23118613
TI  - Double-grating displacement structure for improving the light extraction
      efficiency of LEDs.
AB  - To improve the light extraction efficiency of light-emitting diodes (LEDs),
      grating patterns were etched on GaN and silver film surfaces. The grating
      patterned surface etching enabled the establishment of an LED model with a double
      grating displacement structure that is based on the surface plasmon resonance
      principle. A numerical simulation was conducted using the finite difference time
      domain method. The influence of different grating periods for GaN surface and
      silver film thickness on light extraction efficiency was analyzed. The light
      extraction efficiency of LEDs was highest when the grating period satisfied
      grating coupling conditions. The wavelength of the highest value was also close
      to the light wavelength of the medium. The plasmon resonance frequencies on both
      sides of the silver film were affected by silver film thickness. With increasing
      film thickness, plasmon resonance frequency tended toward the same value and
      light extraction efficiency reached its maximum. When the grating period for the
      GaN surface was 365 nm and the silver film thickness was 390 nm, light extraction
      efficiency reached a maximum of 55%.

PMID- 23118615
TI  - Parietal cortex signals come unstuck in time.
AB  - Humans and other animals are surprisingly adept at estimating the duration of
      temporal intervals, even without the use of watches and clocks. This ability is
      typically studied in the lab by asking observers to indicate their estimate of
      the time between two external sensory events. The results of such studies confirm
      that humans can accurately estimate durations on a variety of time scales.
      Although many brain areas are thought to contribute to the representation of
      elapsed time, recent neurophysiological studies have linked the parietal cortex
      in particular to the perception of sub-second time intervals. In this Primer, we
      describe previous work on parietal cortex and time perception, and we highlight
      the findings of a study published in this issue of PLOS Biology, in which
      Schneider and Ghose characterize single-neuron responses during performance of a
      novel "Temporal Production" task. During temporal production, the observer must
      track the passage of time without anticipating any external sensory event, and it
      appears that the parietal cortex may use a unique strategy to support this type
      of measurement.

PMID- 23118614
TI  - Temporal production signals in parietal cortex.
AB  - We often perform movements and actions on the basis of internal motivations and
      without any explicit instructions or cues. One common example of such behaviors
      is our ability to initiate movements solely on the basis of an internally
      generated sense of the passage of time. In order to isolate the neuronal signals
      responsible for such timed behaviors, we devised a task that requires nonhuman
      primates to move their eyes consistently at regular time intervals in the absence
      of any external stimulus events and without an immediate expectation of reward.
      Despite the lack of sensory information, we found that animals were remarkably
      precise and consistent in timed behaviors, with standard deviations on the order
      of 100 ms. To examine the potential neural basis of this precision, we recorded
      from single neurons in the lateral intraparietal area (LIP), which has been
      implicated in the planning and execution of eye movements. In contrast to
      previous studies that observed a build-up of activity associated with the passage
      of time, we found that LIP activity decreased at a constant rate between timed
      movements. Moreover, the magnitude of activity was predictive of the timing of
      the impending movement. Interestingly, this relationship depended on eye movement
      direction: activity was negatively correlated with timing when the upcoming
      saccade was toward the neuron's response field and positively correlated when the
      upcoming saccade was directed away from the response field. This suggests that
      LIP activity encodes timed movements in a push-pull manner by signaling for both
      saccade initiation towards one target and prolonged fixation for the other
      target. Thus timed movements in this task appear to reflect the competition
      between local populations of task relevant neurons rather than a global timing
      signal.

PMID- 23118616
TI  - Loss of FGF-dependent mesoderm identity and rise of endogenous retinoid
      signalling determine cessation of body axis elongation.
AB  - The endogenous mechanism that determines vertebrate body length is unknown but
      must involve loss of chordo-neural-hinge (CNH)/axial stem cells and mesoderm
      progenitors in the tailbud. In early embryos, Fibroblast growth factor (FGF)
      maintains a cell pool that progressively generates the body and differentiation
      onset is driven by retinoid repression of FGF signalling. This raises the
      possibility that FGF maintains key tailbud cell populations and that rising
      retinoid activity underlies cessation of body axis elongation. Here we show that
      sudden loss of the mesodermal gene (Brachyury) from CNH and the mesoderm
      progenitor domain correlates with FGF signalling decline in the late chick
      tailbud. This is accompanied by expansion of neural gene expression and a similar
      change in cell fate markers is apparent in the human tailbud. Fate mapping of
      chick tailbud further revealed that spread of neural gene expression results from
      continued ingression of CNH-derived cells into the position of the mesoderm
      progenitor domain. Using gain and loss of function approaches in vitro and in
      vivo, we then show that attenuation of FGF/Erk signalling mediates this loss of
      Brachyury upstream of Wnt signalling, while high-level FGF maintains Brachyury
      and can induce ectopic CNH-like cell foci. We further demonstrate a rise in
      endogenous retinoid signalling in the tailbud and show that here FGF no longer
      opposes retinoid synthesis and activity. Furthermore, reduction of retinoid
      signalling at late stages elevated FGF activity and ectopically maintained
      mesodermal gene expression, implicating endogenous retinoid signalling in loss of
      mesoderm identity. Finally, axis termination is concluded by local cell death,
      which is reduced by blocking retinoid signalling, but involves an FGFR
      independent mechanism. We propose that cessation of body elongation involves loss
      of FGF-dependent mesoderm identity in late stage tailbud and provide evidence
      that rising endogenous retinoid activity mediates this step and ultimately
      promotes cell death in chick tailbud.

PMID- 23118617
TI  - Differential age-dependent import regulation by signal peptides.
AB  - Gene-specific, age-dependent regulations are common at the transcriptional and
      translational levels, while protein transport into organelles is generally
      thought to be constitutive. Here we report a new level of differential age
      dependent regulation and show that chloroplast proteins are divided into three
      age-selective groups: group I proteins have a higher import efficiency into
      younger chloroplasts, import of group II proteins is nearly independent of
      chloroplast age, and group III proteins are preferentially imported into older
      chloroplasts. The age-selective signal is located within the transit peptide of
      each protein. A group III protein with its transit peptide replaced by a group I
      transit peptide failed to complement its own mutation. Two consecutive positive
      charges define the necessary motif in group III signals for older chloroplast
      preference. We further show that different members of a gene family often belong
      to different age-selective groups because of sequence differences in their
      transit peptides. These results indicate that organelle-targeting signal peptides
      are part of cells' differential age-dependent regulation networks. The sequence
      diversity of some organelle-targeting peptides is not a result of the lack of
      selection pressure but has evolved to mediate regulation.

PMID- 23118620
TI  - Kelsey's Story.

PMID- 23118621
TI  - A journey from pediatric pharmacokinetics to pharmacogenomics.

PMID- 23118619
TI  - Donor funding for newborn survival: an analysis of donor-reported data, 2002
      2010.
AB  - BACKGROUND: Neonatal mortality accounts for 43% of global under-five deaths and
      is decreasing more slowly than maternal or child mortality. Donor funding has
      increased for maternal, newborn, and child health (MNCH), but no analysis to date
      has disaggregated aid for newborns. We evaluated if and how aid flows for newborn
      care can be tracked, examined changes in the last decade, and considered
      methodological implications for tracking funding for specific population groups
      or diseases. METHODS AND FINDINGS: We critically reviewed and categorised
      previous analyses of aid to specific populations, diseases, or types of
      activities. We then developed and refined key terms related to newborn survival
      in seven languages and searched titles and descriptions of donor disbursement
      records in the Organisation for Economic Co-operation and Development's Creditor
      Reporting System database, 2002-2010. We compared results with the Countdown to
      2015 database of aid for MNCH (2003-2008) and the search strategy used by the
      Institute for Health Metrics and Evaluation. Prior to 2005, key terms related to
      newborns were rare in disbursement records but their frequency increased markedly
      thereafter. Only two mentions were found of "stillbirth" and only nine references
      were found to "fetus" in any spelling variant or language. The total value of non
      research disbursements mentioning any newborn search terms rose from US$38.4
      million in 2002 to US$717.1 million in 2010 (constant 2010 US$). The value of non
      research projects exclusively benefitting newborns fluctuated somewhat but
      remained low, at US$5.7 million in 2010. The United States and the United Nations
      Children's Fund (UNICEF) provided the largest value of non-research funding
      mentioning and exclusively benefitting newborns, respectively. CONCLUSIONS: Donor
      attention to newborn survival has increased since 2002, but it appears unlikely
      that donor aid is commensurate with the 3.0 million newborn deaths and 2.7
      million stillbirths each year. We recommend that those tracking funding for other
      specific population groups, diseases, or activities consider a key term search
      approach in the Creditor Reporting System along with a detailed review of their
      data, but that they develop their search terms and interpretations carefully,
      taking into account the limitations described. Please see later in the article
      for the Editors' Summary.

PMID- 23118618
TI  - Psychosocial factors that shape patient and carer experiences of dementia
      diagnosis and treatment: a systematic review of qualitative studies.
AB  - BACKGROUND: Early diagnosis and intervention for people with dementia is
      increasingly considered a priority, but practitioners are concerned with the
      effects of earlier diagnosis and interventions on patients and caregivers. This
      systematic review evaluates the qualitative evidence about how people accommodate
      and adapt to the diagnosis of dementia and its immediate consequences, to guide
      practice. METHODS AND FINDINGS: We systematically reviewed qualitative studies
      exploring experiences of community-dwelling individuals with dementia, and their
      carers, around diagnosis and the transition to becoming a person with dementia.
      We searched PubMed, PsychINFO, Embase, CINAHL, and the British Nursing Index (all
      searched in May 2010 with no date restrictions; PubMed search updated in February
      2012), checked reference lists, and undertook citation searches in PubMed and
      Google Scholar (ongoing to September 2011). We used thematic synthesis to
      identify key themes, commonalities, barriers to earlier diagnosis, and support
      identified as helpful. We identified 126 papers reporting 102 studies including a
      total of 3,095 participants. Three overarching themes emerged from our analysis:
      (1) pathways through diagnosis, including its impact on identity, roles, and
      relationships; (2) resolving conflicts to accommodate a diagnosis, including the
      acceptability of support, focusing on the present or the future, and the use or
      avoidance of knowledge; and (3) strategies and support to minimise the impact of
      dementia. Consistent barriers to diagnosis include stigma, normalisation of
      symptoms, and lack of knowledge. Studies report a lack of specialist support
      particularly post-diagnosis. CONCLUSIONS: There is an extensive body of
      qualitative literature on the experiences of community-dwelling individuals with
      dementia on receiving and adapting to a diagnosis of dementia. We present a
      thematic analysis that could be useful to professionals working with people with
      dementia. We suggest that research emphasis should shift towards the development
      and evaluation of interventions, particularly those providing support after
      diagnosis.

PMID- 23118622
TI  - Vancomycin for treating cerebrospinal fluid shunt infections in pediatric
      patients.
AB  - Infection is a major cause of CSF shunt failure that places the patient at risk
      of intellectual impairment, development of loculated CSF compartments, and death.
      The purpose of this article is to review the published literature related to
      vancomycin for treatment of pediatric CSF shunt infections. Fifty percent of
      shunt infections appear within 2 months of shunt placement or revision; 90% occur
      within 6 months. Ninety percent of organisms infecting CSF shunting devices are
      Staphylococcus and Streptococcus species. The emergence of methicillin-resistant
      strains of staphylococci has made vancomycin the antibiotic of choice for these
      infections. The usual intravenous regimen is 60 mg/kg/day divided every 6 hours.
      Intraventricular vancomycin should be considered for most patients, starting with
      10 mg daily. CSF vancomycin concentrations should be monitored and dosing
      adjustments made as needed to maintain CSF trough vancomycin concentrations
      between 5 and 20 mg/L.

PMID- 23118623
TI  - Control of Coagulation during Extracorporeal Membrane Oxygenation.
AB  - The use of extracorporeal membrane oxygenation (ECMO) requires maintaining a
      delicate balance between the prevention of thrombosis and the avoidance of
      hemorrhage. Anticoagulation is necessary to maintain circuit flow. It counteracts
      the activation of clotting mechanisms that occurs as a result of the interaction
      between circulating blood and the foreign surfaces of the ECMO equipment as well
      as endothelial damage within the vasculature. Heparin remains the anticoagulant
      of choice; however, the difficulty in adjusting dosages and the risk of
      developing heparin-induced thrombocytopenia have led to the use of alternative
      therapies such as argatroban and lepirudin. In addition, thrombolysis with
      alteplase is now being used in patients who develop clots despite
      anticoagulation. Aminocaproic acid has been used for more than a decade to manage
      or prevent hemorrhage in patients on ECMO, but a new report suggests that
      activated recombinant factor VII may also be useful as a hemostatic agent. Over
      the next decade, it is likely that the role of these newer agents will grow,
      making them important tools in the management of patients on ECMO.

PMID- 23118624
TI  - The accuracy and precision of measuring Lorazepam from three liquid preparations.
AB  - OBJECTIVES: Commercially available lorazepam solution contains both polyethylene
      glycol (PEG) and propylene glycol. When large doses are administered for deep
      sedation in the pediatric intensive care unit (PICU), PEG may cause diarrhea, and
      the accumulation of propylene glycol may result in toxicity. These adverse
      effects may be avoided by preparing a slurry from crushed lorazepam tablets
      suspended in water immediately prior to administration. This slurry, which is
      extemporaneously prepared at bedside by nurses, lacks a suspending agent, and,
      therefore, the rapid settling of drug particles may produce suspensions that are
      not homogeneous. Thus, there may be significant inaccuracy and imprecision in
      dosage measurement. The objective of this study was to compare the accuracy and
      precision of lorazepam dosage measurement from three liquid preparations: 1)
      tablet slurry prepared at bedside by a nurse; 2) lorazepam suspension
      extemporaneously prepared by a pharmacist; and 3) the commercially available
      lorazepam solution. METHODS: Sixteen PICU nurses measured three doses of
      lorazepam (0.5 mg, 1.5 mg, 3.5 mg) in triplicate from each of the three liquid
      preparations using oral syringes. PICU nurses prepared the slurry by mixing
      crushed lorazepam tablet(s) with water and drawing up the appropriate dose in an
      oral syringe. Additionally, nurses drew up the appropriate dose from a pharmacist
      prepared lorazepam suspension (1 mg/mL) and the commercially available lorazepam
      solution (2 mg/mL). All samples were analyzed by HPLC and the groups were
      compared using two-way ANOVA. RESULTS: Dosage accuracy for the slurry (91.2 +/-
      7.8%) and suspension (109.2 +/- 4.9%) were significantly different from the
      commercially available solution (101.5 +/- 3.1%) (P < .05). Imprecision in dosage
      measurement, as determined by the relative standard deviation, was greatest for
      the slurry (8.6%) as compared to the suspension (4.5%) and commercially available
      solution (3.0%). CONCLUSIONS: Dosage measurement from lorazepam slurry and
      suspension led to significant deviation from the intended dose. Dosage
      measurement using the slurry was the least precise among the three preparations.

PMID- 23118625
TI  - Utility of anti-xa monitoring in children receiving enoxaparin for therapeutic
      anticoagulation.
AB  - Although enoxaparin is used to treat thromboembolism in children, current
      treatment guidelines are largely extrapolated from adults. The objectives of this
      study were to determine: i) correlation between enoxaparin dose and anti-factor
      Xa (anti-Xa) level, ii) intra-patient variability, and iii) whether dose or anti
      Xa level is a predictor of outcomes. A retrospective chart review was conducted
      on all hospitalized patients receiving enoxaparin in a tertiary care pediatric
      institution. Simple linear regression, coefficient of variation (CV), and
      Student's t-test were used to analyze the objectives. Eighty treatment courses
      with interpretable anti-Xa levels were analyzed. Mean patient age was 6.5 years.
      Mean enoxaparin dose was 1.10 mg/kg q12h. Correlation between initial dosing and
      anti-Xa level was poor; R(2) = 0.0307 and 0.0237 for patients > 2 months with and
      without cardiac or renal diseases, respectively. Four out of seven patients <= 2
      months of age compared to 4/32 patients > 2 months had a CV > 40%. Similarly,
      4/12 cardiac patients compared to 4/27 non-cardiac patients had a CV > 40%.
      Neither dose nor anti-Xa level predicted treatment success or adverse reactions
      (P > .05). These results suggest a need to reexamine the use of anti-Xa levels
      for guiding enoxaparin therapy. Further prospective studies are warranted to
      clarify whether routine or selective anti-Xa monitoring should be recommended in
      pediatric patients.

PMID- 23118626
TI  - Depression in Children with HIV Infection: A Case Series.
AB  - About 46,000 individuals younger than 25 years of age currently have a diagnosis
      of human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
      (AIDS). During their lifetime, approximately one-third of patients with HIV may
      develop depression. While antidepressants have been studied in adults with HIV,
      no data exist to support the use of antidepressants in children and adolescents
      with HIV. We report a case series of seven pediatric patients with HIV who were
      prescribed antidepressants. Six of seven patients had mild to moderate
      improvements in depressive symptoms. None of our patients experienced any
      suicidal ideations, and adverse events were minor. No drug-drug interactions were
      reported, and no significant changes in CD4 counts, CD4 percentages, or viral
      loads occurred during antidepressant therapy. Placebo-controlled, randomized
      studies are needed to confirm our results in this patient population.

PMID- 23118627
TI  - Treatment of seizures in newborns: the dilemma of starting the right drug, at the
      right time, in the right doses, and monitoring the right endpoints.

PMID- 23118628
TI  - Postnatal Steroids to Treat Chronic Lung Disease in Preterm Infants: Is it Ever
      Justified?

PMID- 23118629
TI  - A history of neonatal medicine-past accomplishments, lessons learned, and future
      challenges. Part 1-the first century.
AB  - This is the first of two articles that will review the history of neonatal
      medicine. This article will describe the beginnings of the modern era of newborn
      medicine, review pharmacological misadventures, and describe recent advances in
      the fields of neonatal and perinatal medicine.

PMID- 23118630
TI  - Survey of the use of corticosteroids among neonatal intensive care units for the
      prevention or treatment of bronchopulmonary dysplasia.
AB  - OBJECTIVE: To survey neonatal intensive care units (NICUs) at academic medical
      centers to determine the current use of inhaled and systemic corticosteroids for
      the prevention or treatment of bronchopulmonary dysplasia (BPD). METHODS: A
      survey was developed to evaluate aspects of systemic and inhaled corticosteroid
      use in neonates. Eighty academic medical centers with neonatal/perinatal medicine
      fellowship programs were surveyed. Neonatology fellows or NICU clinical
      pharmacists with direct patient care activities responded via telephone, fax or e
      mail. RESULTS: Fifty-three institutions responded to the survey (66.3% response
      rate). Twenty-nine percent of respondents (n = 15) use corticosteroids for
      prevention of BPD. Systemic corticosteroids are used by 6% of respondents (n = 3)
      and inhaled corticosteroids are used by 14% of respondents (n = 7) for
      prevention. Ten percent of respondents (n = 5) use either systemic or inhaled
      corticosteroids for prevention. Eighty-eight percent of respondents (n = 45) use
      corticosteroids for treatment of BPD. Systemic corticosteroids are used by 10% of
      respondents (n = 5) and inhaled corticosteroids are used by 10% of respondents (n
      = 5) for treatment. Sixty-nine percent of respondents (n = 35) use either
      systemic or inhaled corticosteroids for treatment. There was a wide variability
      in drug, dose, titration, taper, administration, and duration of therapy
      reported. CONCLUSIONS: These results indicate that systemic and inhaled
      corticosteroids are commonly used by practitioners for the prevention or
      treatment of BPD despite a recommendation against the routine use of systemic
      corticosteroids by the American Academy of Pediatrics' (AAP) Committee on Fetus
      and Newborn and the Canadian Paediatric Society's Fetus and Newborn Committee
      from February 2002.

PMID- 23118631
TI  - Moderate Dose Inhaled Budesonide Disguising Symptoms of Addison's Disease in An
      Asthmatic Boy with Silent Celiac Disease.
AB  - Inhaled corticosteroids are first-line treatment for asthma. Moderate doses of
      budesonide have been supposed not to affect hypothalamic-pituitary-adrenal axis
      function. We report the case of a boy with asthmatic symptoms and a late
      diagnosis of celiac disease, in whom inhaled budesonide in a dose used in
      conventional asthma therapy seems to have been systemically absorbed in amounts
      large enough to temporarily disguise the symptoms of a developing adrenal
      insufficiency. Inhaled corticosteroids in a dose used in standard asthma therapy
      seem to have the potential of disguising a developing Addison's disease.
      Furthermore, celiac disease, especially if diagnosed in late childhood, may be
      associated with Addison's disease causing a complex symptom pattern.

PMID- 23118632
TI  - The use of systemic fluoroquinolones in pediatrics.

PMID- 23118633
TI  - History of neonatal medicine-limitations in studies, guidelines, and resources
      impact progress.

PMID- 23118634
TI  - A History of Neonatal Medicine-Past Accomplishments, Lessons Learned, and Future
      Challenges: Part II-The 1990s, the New Millennium, Future Challenges.
AB  - This is the second of two articles reviewing the history of newborn medicine.
      This article will discuss recent accomplishments in the field of newborn
      medicine, current health outcome data, and future challenges facing the fields of
      neonatal and perinatal medicine.

PMID- 23118635
TI  - Management of allergic rhinitis.
AB  - Allergic rhinitis is the most common chronic childhood disease. Reduced quality
      of life is frequently caused by this IgE-mediated disease, including sleep
      disturbance with subsequent decreased school performance. Asthma and exercise
      induced bronchospasm are commonly seen concurrently with allergic rhinitis, and
      poorly controlled allergic rhinitis negatively affects asthma outcomes.
      Nonsedating antihistamines or intranasal azelastine are effective agents to
      manage allergic rhinitis, often in combination with oral decongestants. For
      moderate to severe persistent disease, intranasal corticosteroids are the most
      effiective agents. Some patients require concomitant intranasal corticosteroids
      and nonsedating antihistamines for optimal management. Other available agents
      include leukotriene receptor antagonists, intranasal cromolyn, intranasal
      ipratropium, specific immunotherapy, and anti-IgE therapy.

PMID- 23118636
TI  - Nephrotoxicity with combination vancomycin-aminoglycoside therapy.
AB  - OBJECTIVES: The purpose of this paper is to review the medical literature
      regarding vancomycinaminoglycoside induced nephrotoxicity in the pediatric
      population.  METHODS MEDLINE: (1966 through June 2005), EMBASE (1980 through 1st
      quarter 2005), and International Pharmaceutical Abstracts databases were reviewed
      using appropriate search terms for articles related to nephrotoxicity with
      vancomycin and aminoglycoside use. Case reports, letters to editors,
      retrospective and prospective studies evaluating nephrotoxicity with the agents
      in pediatric patients were compiled and summarized. Studies in animals and adults
      were also briefly reviewed. RESULTS: One case report, two letters to editors, one
      retrospective study, and two prospective studies evaluated the nephrotoxicity of
      combination aminoglycoside and vancomycin therapy in pediatric patients. The
      collective number of patients in the reports was 165. Patients ranged in age from
      3 days to 19 years old. Four out of the six reports, including all of the
      prospective studies, concluded that combination therapy does not potentiate
      nephrotoxicity. CONCLUSIONS: Although vancomycin and the aminoglycosides have
      been associated with drug induced nephrotoxicity, reports in the literature do
      not appear to support the idea that the combination of vancomycin and an
      aminoglycoside is more nephrotoxic than either medication alone.

PMID- 23118637
TI  - Protein and nitrogen metabolism changes following closed head injury or
      cardiothoracic surgery in pediatric patients.
AB  - OBJECTIVE: We compared markers of protein metabolism between children who had a
      controlled injury and an acute traumatic event. Significant protein catabolism
      occurs after acute severe injury. During surgery the injury is controlled and the
      degree of subsequent catabolism may be blunted. METHODS: This was a prospective,
      unblinded observational study in 10 children 2 to 12 years old with a closed head
      injury (CHI) and an admission Physiologic Stability Index of >= 10 and in 10
      children who underwent elective cardiothoracic surgery (CTS). Nutrient intake,
      nitrogen balance, serum albumin and prealbumin, urinary 3-methylhistidine
      excretion, and 3-methylhistidine to creatinine ratios were evaluated on days 1,
      2, 3, 4, and 10 after injury. RESULTS: Nutrient intake was similar in both groups
      on study days 1-4 and did not meet estimated needs. By day 10, 7 patients in the
      CTS group and 2 patients in the CHI group had been discharged home. The 3 CTS
      patients were still in the ICU while the 8 hospitalized CHI patients had been
      transferred to the floor. Compared to the CTS group, nitrogen balance in the CHI
      group was lower on day 1. On day 10, nitrogen balance and prealbumin were greater
      in the CHI group than in the CTS group, consistent with recovery and increased
      nutrient intake. CONCLUSIONS: Markers of protein metabolism follow similar
      patterns after CTS or CHI in children. However, markers of protein metabolism
      indicate more severe catabolism soon after injury in CHI.

PMID- 23118638
TI  - Pediatric palliative care.
AB  - Pediatric palliative care provides benefit to children living with life
      threatening or terminal conditions. Palliative care should be available to all
      seriously ill children. Palliative care includes the treatment of symptoms such
      as pain, nausea, dyspnea, constipation, anorexia, and sialorrhea. This care can
      occur in a variety of settings, from home to hospice to hospital, and must
      include bereavement care and follow up after the death of a child. There are many
      challenges in pediatric palliative care, but continued research into this
      important area of pediatrics will lead to improvements in the care of children
      with life-threatening illnesses.

PMID- 23118639
TI  - New Antiretroviral Therapies for Pediatric HIV Infection.
AB  - Human immunodeficiency virus (HIV) infection and acquired immunodeficiency
      syndrome affect millions of children worldwide. The development of antiretroviral
      therapy has significantly improved the morbidity and mortality of pediatric
      patients infected with HIV. Currently, 4 classes of antiretroviral agents exist:
      nucleoside / nucleotide reverse transcriptase inhibitors, non-nucleoside reverse
      transcriptase inhibitors, protease inhibitors, and entry inhibitors. A total of
      21 single-entity antiretroviral agents and 4 co-formulated antiretroviral
      products hold Food and Drug Administration (FDA) approval for treatment of HIV-1
      infection. However, not all of these agents are indicated for use in patients
      less than 18 years of age. Since the year 2000, 7 new antiretroviral agents
      (atazanavir, emtricitabine, enfuvirtide, fosamprenavir, lopinavir/ritonavir,
      tenofovir, and tipranavir) have been approved by the FDA for use in adult
      patients as part of combination therapy for the treatment of HIV-1 infection.
      Although only 3 of these newer agents (emtricitabine, enfuvirtide, and
      lopinavir/ritonavir) are currently FDA approved for use in pediatric patients,
      pediatric clinical studies of the other 4 new agents are currently underway. The
      purpose of this article is to review these 7 new antiretroviral agents and
      describe their roles in the treatment of pediatric HIV infection. For each drug,
      the following information will be addressed: FDA-approved indication and age
      groups, clinical efficacy, pharmacokinetics, adverse drug reactions, clinically
      relevant drug interactions, pediatric and adult dosing, dosage forms,
      administration, and place in the treatment of pediatric HIV infection.

PMID- 23118640
TI  - Oxcarbazepine: a brief review.
AB  - Oxcarbazepine is a new anticonvulsant with an active metabolite. It is approved
      as mono- or adjunctive therapy for partial seizures in adults and children older
      than 4 years of age and as adjunctive therapy in children 2 years and older. Its
      spectrum of anticonvulsant activity is comparable to carbamazepine, but it has an
      improved pharmacokinetic profile, is better tolerated and is associated with few
      clinically significant drug-drug interactions.

PMID- 23118641
TI  - Impact of a pediatric clinic-based multidisciplinary asthma education and
      management program.
AB  - OBJECTIVE: The objective of this study was to determine if a multidisciplinary
      asthma education and management program within a general pediatric clinic impacts
      clinical outcomes of children with asthma. METHODS: An asthma education and
      management clinic was started by a general pediatrician, a pharmacist, and a
      nurse. At a patient's initial clinic visit, data were collected summarizing
      hospitalizations, emergency department visits, and number of systemic
      corticosteroid courses for the previous year. The same data were collected at
      each subsequent visit. A retrospective review of this data was performed for
      patients who enrolled in the clinic between February 1999 and 2002 to compare
      outcomes between the year before enrollment in the clinic and the following year.
      Patients were included if they received follow-up for at least one year. RESULTS:
      Fifty-seven patients with a mean age of 8.5 years qualified for data analysis.
      Forty-eight percent of the study population was classified as having moderate
      persistent asthma, and 11% of patients were severe persistent. Compared to the
      year prior to clinic enrollment, the number of hospitalizations per patient
      decreased by 82% (P < .001). Emergency department visits decreased by 81% (P <
      .001). The number of systemic corticosteroid courses decreased by 72% (P <
      0.001). CONCLUSIONS: Patient enrollment in a general pediatric clinic-based
      multidisciplinary asthma education and management program decreases
      hospitalizations, emergency department visits, and systemic corticosteroid
      exposure.

PMID- 23118642
TI  - A historical perspective on pharmacological studies of gentamicin for therapy of
      neonatal meningitis.

PMID- 23118643
TI  - Ethical considerations in the randomized evaluation of propofol safety.

PMID- 23118644
TI  - Propofol-related infusion syndrome in critically ill pediatric patients:
      coincidence, association, or causation?
AB  - Over the past two decades numerous reports have described the development of a
      propofol-related infusion syndrome (PRIS) in critically ill adult and pediatric
      patients who received continuous infusion propofol for anesthesia or sedation.
      The syndrome is generally characterized by progressive metabolic acidosis,
      hemodynamic instability and bradyarrhythmias that are refractory to aggressive
      pharmacological treatments. PRIS may occur with or without the presence of
      hepatomegaly, rhabdomyolysis or lipemia. To date, the medical literature contains
      accounts of 20 deaths in critically ill pediatric patients who developed features
      consistent with PRIS. These reports have generated considerable discussion and
      debate regarding the relationship, if any, between propofol and a constellation
      of clinical symptoms and features that have been attributed to its use in
      critically ill pediatric patients. This paper reviews the literature concerning
      PRIS, its clinical presentation, proposed mechanisms for the syndrome, and
      potential management should the syndrome occur.

PMID- 23118645
TI  - A comparative pharmacoeconomic assessment of two surfactants for the prevention
      of respiratory distress syndrome.
AB  - OBJECTIVE: The use of exogenous surfactants among preterm infants for the
      prevention and treatment of respiratory distress syndrome (RDS) has led to
      economic and cost-effectiveness evaluations of these products. Lucinactant
      (Surfaxin), a novel, peptide-based, synthetic surfactant, has been shown to
      significantly reduce RDS-related mortality, compared with the most commonly
      prescribed animal-derived surfactant, beractant (Survanta). Infants who survive
      expend significant healthcare resources; therefore, the impact of improved
      survival through 1-year corrected age was evaluated in a prospectively defined
      pharmacoeconomic analysis. The objectives of this study were to estimate the
      healthcare resource utilization, economic impact, and cost-effectiveness of
      lucinactant versus beractant for the prevention of RDS among surviving very low
      birth weight (VLBW) preterm infants weighing 600 to 1250 grams. METHODS: A
      decision-analytic model was developed to compare the healthcare resource
      utilization, economic impact, and cost-effectiveness of lucinactant versus
      beractant. RESULTS: Infants who received lucinactant had fewer neonatal intensive
      care unit (NICU) days and fewer NICU days on mechanical ventilation compared with
      infants who received beractant. Total healthcare costs for the initial stay in
      the NICU were lower by $8,803 among infants who received lucinactant compared
      with infants who received beractant. The incremental cost per life saved was
      $40,309 for lucinactant compared with beractant. CONCLUSIONS: Administration of
      lucinactant to surviving VLBW preterm infants resulted in fewer NICU days and
      fewer NICU days on mechanical ventilation compared with beractant. Fewer NICU
      days translates into lower total costs among infants who received lucinactant.
      This comprehensive pharmacoeconomic analysis indicates that lucinactant is a cost
      effective therapy for the prevention of RDS among preterm infants.

PMID- 23118646
TI  - Antibiotic therapy for infective endocarditis in childhood.
AB  - Infective endocarditis is relatively uncommon in childhood, but its epidemiology
      has changed in the past three to four decades and its incidence has been
      increasing in recent years. With the improved survival rates of children with
      congenital heart diseases and the overall decreased frequency of rheumatic
      valvular heart disease in developed countries, congenital cardiac abnormalities
      now represent the predominant underlying condition for infective endocarditis in
      children over the age of two years in Western Europe and Northern America.
      Moreover, the complex management of neonatal and pediatric intensive care unit
      patients has increased the risk of catheter-related endocarditis. More
      specifically, the surgical correction of congenital heart alterations is
      associated with the risk of postoperative infections. Endocarditis in children
      may be difficult to diagnosis and manage. Emerging resistant bacteria, such as
      methicillin- or vancomycin-resistant staphylococci and vancomycin-resistant
      enterococci, are becoming a new challenge for conventional antibiotic therapy.
      Newer antimicrobial compounds recently introduced in clinical practice, such as
      streptogramins and oxazolidinones, may be effective alternatives in children with
      endocarditis sustained by Gram-positive cocci resistant to glycopeptides. Home
      intravenous therapy has become an acceptable approach for stable patients who are
      at low risk for embolic complications. However, further clinical studies are
      needed in order to assess efficacy and safety of these antimicrobial agents in
      children. This review should help outline the most appropriate antimicrobial
      treatments for infective endocarditis in children.

PMID- 23118647
TI  - An open label comparison of calfactant and poractant alfa administration traits
      and impact on neonatal intensive care unit resources.
AB  - OBJECTIVE: To compare calfactant (CA) and poractant alfa (PA) administration
      traits, short-term clinical responses, and resource use in the neonatal
      respiratory distress syndrome (RDS) setting. METHODS: An open label series of 277
      (213 PA and 64 CA) infants was evaluated for 445 administrations. Registered
      respiratory therapists collected patient, surfactant administration, and
      postadministration clinical data. Economic analysis involved labor costs of
      surfactant administration and usage, wastage, and product average wholesale
      price. Analysis utilized the Mann-Whitney rank sum test for differences in
      administration time and either the chi-square or Fisher's exact test for
      categorical variables. RESULTS: PA had a statistically lower bedside
      administration time than CA (3.8 minutes vs. 5.3 minutes; P = .006) and a higher
      percentage of doses administered in less than five minutes (58.9% vs. 4.3%; P <
      .001). Doses administered per patient were similar (1.67 vs. 1.72). PA and CA
      were similar in time to recovery (81.4% vs. 74.3%), percent desaturation (24.8%
      vs. 26.7%), and bradycardia (3.8% vs. 8.5%). Reflux was significantly higher
      (13.2% vs. 3.5%; P < .001) with CA. Economic analyses found total administration
      costs per dose were $2.21 for PA and $3.08 for CA. Mean wastage costs were
      $141.21 for PA and $337.34 for CA (P < .001). CONCLUSIONS: PA appeared to utilize
      fewer neonatal intensive care unit resources than CA due to reduced
      administration time and less wastage of drug product. Future studies should more
      closely evaluate time, resource, wastage, and post-administrative clinical
      effects to fully assess the impact of surfactant products in this setting.

PMID- 23118648
TI  - Prospective randomized double-blind placebo controlled trial of recombinant human
      erythropoietin administration to reduce blood transfusions in anemic pediatric
      intensive care patients.
AB  - OBJECTIVE: The purpose of this study was to determine if the number of red blood
      cell (RBC) transfusions anemic pediatric intensive care unit patients receive
      could be reduced by the prophylactic administration of recombinant human
      erythropoietin (rHuEPO). METHODS: This was a randomized, double-blind placebo
      controlled trial. Patients were randomized to receive either intravenous rHuEPO
      300 units/kg/day or placebo. Both groups received elemental iron 6 mg/kg/day.
      RESULTS: Twenty-seven patients, ages 1 month to 13 years, were enrolled. Baseline
      hematocrit (Hct), reticulocyte count, and erythropoietin concentration were
      similar between the two groups. Three patients randomized to rHuEPO received 1
      RBC transfusion each, and 4 patients randomized to placebo received 9
      transfusions total (P = .68). The end-of-study Hct was not significantly
      different between the rHuEPO and placebo groups, 30.3 +/- 3.6 and 26.8 +/- 4.8,
      respectively (P = .06). Additionally, neither the % Hct change (baseline to
      final), nor the % reticulocyte change (baseline to final), was statistically
      different between the two groups. CONCLUSION: In this small group of anemic
      pediatric intensive care unit patients, prophylactic rHuEPO administration did
      not reduce the number of patients who received RBC transfusions. Furthermore, it
      did not significantly increase Hct or reticulocyte count when compared to
      placebo.

PMID- 23118649
TI  - Evaluation of conformity of a first prescription of lipid-based formulation of
      amphotericin B in a university-teaching pediatric hospital.
AB  - OBJECTIVE: Invasive fungal infections are an important cause of morbidity and
      mortality in immunodeficient children. Amphotericin B is an important therapeutic
      agent for the treatment of invasive fungal infections but is associated with
      significant toxicities and high acquisition costs. The purpose of this study was
      to evaluate physician adherence to a local guideline for the use of lipid-based
      amphotericin B. METHODS: The study was approved through Pharmacology &
      Therapeutics (P&T) committee activities. A retrospective drug utilization review
      (DUR) was conducted. All orders written between January 1, 2003, and December 31,
      2004, were reviewed. Demographic and descriptive clinical data were collected as
      well as variables related to the drug order process. Conformity rates were
      calculated for the primary objective criteria (authorized prescribers -
      infectious disease members; recommended drug of choice-Abelcet; accepted
      indications; and presence of underlying conditions). RESULTS: A total of 109
      orders for 70 patients were reviewed by a single research assistant for a 2-year
      period. Global conformity rate for all four criteria was calculated at 7.3%. Non
      conformity was mostly associated with the absence of underlying conditions (e.g.,
      prerenal insufficiency or presence of nephrotoxicity due to amphotericin B
      desoxycholate) in 84.5% of the cases. Infusionrelated adverse drug reactions
      partly explained a switch to a non-formulary lipid-based amphotericin B product.
      External factors (newly published results since the adoption of the guideline and
      continuous marketing practices) and internal factors (availability of non
      formulary process, inefficient DUR process) could have contributed to non
      adherence to a local guideline. CONCLUSION: This study shows low adherence to P&T
      committee drug guidelines on lipid-based amphotericin B. Continuous and efficient
      DUR processes should be in place to monitor drug guideline adherence.

PMID- 23118650
TI  - Surfactants in the management of respiratory distress syndrome in extremely
      premature infants.
AB  - Respiratory distress syndrome (RDS) is primarily due to decreased production of
      pulmonary surfactant, and it is associated with significant neonatal morbidity
      and mortality. Exogenous pulmonary surfactant therapy is currently the treatment
      of choice for RDS, as it demonstrates the best clinical and economic outcomes.
      Studies confirm the benefits of surfactant therapy to include reductions in
      mortality, pneumothorax, and pulmonary interstitial emphysema, as well as
      improvements in oxygenation and an increased rate of survival without
      bronchopulmonary dysplasia. Phospholipids (PL) and surfactant-associated proteins
      (SP) play key roles in the physiological activity of surfactant. Different types
      of natural and synthetic surfactant preparations are currently available. To
      date, natural surfactants demonstrate superior outcomes compared to the synthetic
      surfactants, at least during the acute phase of RDS. This disparity is often
      attributed to biochemical differences including the presence of surfactant
      associated proteins in natural products that are not found in the currently
      available synthetic surfactants. Comparative trials of the natural surfactants
      strive to establish the precise differences in clinical outcomes among the
      different preparations. As new surfactants become available, it is important to
      evaluate them relative to the known benefits of the previously existing
      surfactants. In order to elucidate the role of surfactant therapy in the
      management of RDS, it is important to review surfactant biochemistry,
      pharmacology, and outcomes from randomized clinical trials.

PMID- 23118651
TI  - The role of continuous positive airway pressure therapy in the management of
      respiratory distress in extremely premature infants.
AB  - The use of mechanical ventilation for the treatment of respiratory distress
      syndrome (RDS) in low birth weight infants may cause barotrauma, volutrauma, and
      chronic lung disease. Different continuous positive airway pressure (CPAP)
      delivery systems exist, each with its own practical and clinical advantages and
      disadvantages. CPAP can be used as either a primary or an adjunctive respiratory
      support for RDS. Research demonstrates that CPAP decreases the incidence of
      respiratory failure after extubation. Clinical trials indicate that the optimal
      management of neonatal RDS consists of early surfactant treatment followed
      quickly by extubation and stabilization on CPAP. Early surfactant treatment
      combined with CPAP reduces the need for mechanical ventilation, compared to later
      surfactant treatment. Evidence suggests a synergistic effect between early
      surfactant administration and rapid extubation to nasal CPAP.

PMID- 23118652
TI  - Pharmacoeconomics of surfactant therapy.
AB  - Surfactant therapy has become an integral part of the standard of care for
      treating premature infants with respiratory distress syndrome (RDS). Institutions
      that routinely treat this patient population have to select a surfactant based
      upon clinical and pharmacoeconomic considerations. Pharmacoeconomic studies have
      established the cost-effectiveness of individual agents based on a variety of
      factors, including length of hospitalization, mortality odds ratio, and other
      direct medical costs. These studies evaluated infants with weights between 600
      and 2000 grams and survival periods between 28 days and 1 year. With the cost
      effectiveness of surfactants already established as being far superior to no
      treatment, trials have evolved to compare the available surfactants. Two studies
      have supported the cost-effectiveness of beractant compared to colfosceril or
      calfactant. Two others demonstrated lower resource utilization associated with
      poractant alfa as compared to beractant or calfactant. Evolving treatment
      approaches in the management of neonatal RDS, such as recent data suggesting
      continuous positive airway pressure as an alternative to mechanical ventilation
      for respiratory support, have defined the need to further evaluate the impact of
      such strategies upon surfactant and resource utilization.

PMID- 23118653
TI  - Practical considerations in the selection and use of pulmonary surfactant therapy
      for neonatal respiratory distress syndrome in the intensive care setting.
AB  - Pulmonary surfactant is the treatment of choice for neonatal respiratory distress
      syndrome, as it significantly reduces infant morbidity and mortality. Extensive
      clinical trials compare the surfactant products and their optimal usage, but
      often the practical administration issues are less frequently discussed. Herein,
      a panel of respiratory therapists and neonatal nurse practitioners share their
      experience regarding surfactant usage. According to the panelists, the primary
      criteria for surfactant selection are the ability to rapidly decrease ventilatory
      requirements toward extubation, a low incidence of adverse effects, cost
      effectiveness, and ease of use. In most cases, surfactant is most efficacious
      when given as early as possible where indicated. The surfactant products differ
      in their storage, handling, preparation, and administration traits, and this may
      affect rapid dosing of the surfactant during acute treatment. During and after
      administration, optimal response to therapy depends on efficient management of
      ventilator settings, which requires vigilant monitoring of the infant. Common
      adverse effects include endotracheal tube reflux, bradycardia, and desaturation.
      Using a surfactant which requires a small dosing volume may decrease the
      incidence of these adverse effects. An emerging trend in clinical practice is the
      quick extubation of the infant to nasal continuous positive airway pressure after
      surfactant administration. This practice can reduce the need for ventilation and
      reduce the risk of ventilator-related lung damage. Nebulization of surfactant may
      be a future avenue of delivery, but further research is required to determine its
      precise role. The practical considerations summarized in this discussion may be
      useful for other clinicians in their own practice.

PMID- 23118654
TI  - Why is the platelet count low: should I be concerned about heparin-induced
      thrombocytopenia?

PMID- 23118655
TI  - Pharmacogenomics of adverse effects of anti-leukemic agents in children.

PMID- 23118657
TI  - A systematic review of the pharmacokinetics of antiepileptic drugs in neonates
      with refractory seizures.
AB  - BACKGROUND: Neonatal seizures are associated with neurological sequelae and an
      increased risk of epilepsy later in life. Phenobarbital and phenytoin remain the
      antiepileptic drugs (AEDs) most commonly used to treat neonatal seizures, despite
      their suboptimal effectiveness and safety. As a result, other AEDs, such as
      levetiracetam and topiramate, are often used in neonates with refractory
      seizures, despite limited data and off-label use. OBJECTIVES: To systematically
      review published pharmacokinetic data for second-line AEDs used in neonates with
      seizures and to provide dosing recommendations for these agents in the neonatal
      population. METHODS: A literature search was conducted in PubMed (1949-May 2012),
      Medline (1950-May 2012), and Embase (1980-May 2012). Each study was ranked
      according to the quality of evidence it provided, based on the classification
      system developed by the US Preventive Services Task Force. Information extracted
      from each study included study design, number of subjects, gestational and
      postnatal age, AED dosage regimen, pharmacokinetic parameters, pharmacokinetic
      model, AED serum concentrations, and sampling times. RESULTS: Nineteen relevant
      pharmacokinetic studies involving a total of 8 different drugs were identified.
      No prospective, randomized, controlled studies (level I evidence) or
      nonrandomized controlled studies (level II-I evidence) were identified; 2 studies
      were prospective, nonrandomized, uncontrolled (cohort) studies (level II-2
      evidence), 11 studies obtained evidence from multiple time series (level II-3
      evidence), and 6 studies were case reports or descriptive studies (level III
      evidence). CONCLUSIONS: There are limited pharmacokinetic data for the use of
      carbamazepine, levetiracetam, lidocaine, paraldehyde, topiramate, valproic acid,
      and vigabatrin for neonates with seizures refractory to treatment with first-line
      antiepileptic agents. Further research is needed to elucidate target AED serum
      concentrations (if any) required to optimize effectiveness and minimize dose
      related adverse effects in neonates.

PMID- 23118658
TI  - Relationship of caffeine dosing with serum alkaline phosphatase levels in
      extremely low-birth-weight infants.
AB  - OBJECTIVE: To determine whether patients receiving higher doses of caffeine have
      increased alkaline phosphatase (ALP) levels, as a biomarker for osteopenia.
      METHODS: This descriptive, retrospective study included 152 extremely low-birth
      weight infants (ie, <1 kg) admitted from January 1, 2007, to September 30, 2009,
      who received caffeine for >2 weeks. Patients were divided into a low-dose (<7.5
      mg/kg/day) and high-dose (>=7.5 mg/kg/day) group based on maximum caffeine dose
      received. The primary objective was to compare peak ALP levels between groups.
      Secondary objectives included a comparison of caffeine regimens and risk factors
      for osteopenia between groups and identification of factors significantly related
      to increase in ALP. Between-group analysis was performed using the chi-squared or
      Fisher exact test and Wilcoxon Mann-Whitney median test or t-tests where
      appropriate. A linear regression model was used, with peak ALP as the dependent
      variable. RESULTS: A majority of the patients (n=122) were included in the high
      dose caffeine group. No significant difference in maximum ALP level between
      groups (median, 599.5, versus 602.5 units/L, p=0.72). Gestational age and birth
      weight were inversely related to ALP, whereas parenteral nutrition duration was
      directly related. No significant relationship between caffeine dose and ALP was
      identified. CONCLUSIONS: In this preliminary study, using ALP as a biochemical
      marker for bone turnover, there does not appear to be a dose-related effect
      between ALP and caffeine dose.

PMID- 23118656
TI  - Heparin-induced thrombocytopenia in the pediatric population: a review of current
      literature.
AB  - Heparin-induced thrombocytopenia is a rare and serious reaction to unfractionated
      heparin and low-molecular-weight heparins in children. Quick recognition,
      discontinuation of heparin, and subsequent treatment with an alternative
      anticoagulant are essential steps to prevent serious complications such as
      thrombus and limb amputation. The purpose of this review is to describe the
      clinical features of heparin-induced thrombocytopenia in children and to
      summarize the data available for its management. This paper summarizes data and
      relates the use of direct thrombin inhibitors with clinical outcomes. A
      literature search was conducted with Ovid, using the key terms argatroban,
      bivalirudin, hirulog, danaparoid, lepirudin, direct thrombin inhibitor, heparin
      induced thrombocytopenia, thrombosis, warfarin, and fondaparinux. Articles were
      excluded if they were classified as editorials, review articles, or conference
      abstracts or if they involved patients 18 years of age or older or described
      disease states not related to thrombosis. Nineteen articles containing 33 case
      reports were identified and evaluated for this review. Of the 33 cases, 14, 10,
      4, and 2 cases described the use of lepirudin, danaparoid, argatroban, and
      bivalirudin, respectively. Two cases did not report the type of anticoagulant
      used, and 1 case used aspirin. The most commonly reported complication was
      bleeding.

PMID- 23118659
TI  - Evaluation of serum concentrations achieved with an empiric once-daily tobramycin
      dosage regimen in children and adults with cystic fibrosis.
AB  - OBJECTIVES: To assess the ability of an empiric once-daily dosing (ODD)
      tobramycin regimen to achieve desired serum concentrations in patients with
      cystic fibrosis (CF); to determine an optimal dosage regimen, using
      pharmacodynamic parameters; and to evaluate clinical response, adverse effects,
      and patient/parent satisfaction with ODD. METHODS: This was a prospective single
      center trial in patients with CF who are 5 years of age and older requiring
      intravenous antibiotics. Tobramycin, 10 mg/kg every 24 hours, was infused over 60
      minutes, and two serum concentrations were analyzed using 1-compartment
      pharmacokinetic modeling. Simulations were performed to identify dosage regimens
      that maximized desired pharmacodynamic parameters. Other data included
      demographics, symptoms, spirometry, adverse events, and satisfaction with ODD.
      RESULTS: A total of 14 children and 11 adults completed the study. Empiric doses
      resulted in mean peak tobramycin concentrations of 28.7 +/- 5.5 mg/L and
      undetectable trough concentrations. Only 42% of patients achieved desired peak
      serum concentrations (20-30 mg/L) with the empiric regimen. A regimen of 12 mg/kg
      every 24 hours would achieve modified pharmacodynamic goals with an acceptable
      peak range of 20 to 35 mg/L. Forced expiratory volume in 1 second improved in 15
      of 20 (75%) patients with ODD. Two patients experienced reversible vestibular
      adverse effects attributed to tobramycin. All patients were satisfied or very
      satisfied with ODD because of convenience and ease of use. CONCLUSIONS: An
      empiric tobramycin regimen of 10 mg/kg every 24 hours did not achieve desired
      serum concentrations for most patients, although all patients demonstrated
      clinical improvement. Desired tobramycin concentrations with modified
      pharmacodynamic goals could be achieved by using an empiric dosage of 12 mg/kg
      every 24 hours. Prospective evaluation of this regimen with individualized
      patient monitoring is needed to ensure safety and efficacy and to monitor the
      effects on microbial resistance patterns.

PMID- 23118660
TI  - Initial experience with conivaptan use in critically ill infants with cardiac
      disease.
AB  - OBJECTIVE: Arginine vasopressin (AVP) is the primary regulator of free water
      retention through its interactions with the AVP type 2 receptor (V(2)). As
      opposed to the natriuresis and diuresis that occur with loop and thiazide
      diuretics, conivaptan is an AVP V(1A)/V(2) receptor antagonist, which enhances
      free water excretion while minimizing sodium loss. We report our preliminary
      experience with conivaptan to promote diuresis in infants with functional or
      structural cardiac disease. METHODS: A retrospective cohort study was conducted
      of infants who had received conivaptan from August 2007 to January 2008. A
      loading dose of conivaptan (0.3-0.6 mg/kg) was followed by a continuous infusion
      of 0.01-0.02 mg/kg/hr for 24 hours. Sodium, potassium, chloride, blood urea
      nitrogen (BUN), creatinine, bicarbonate, and urine output were measured prior to
      the start of conivaptan and at 24 hours after initiation of the infusion.
      RESULTS: Conivaptan was administered intravenously on 6 occasions to 5 patients
      with hypervolemic hyponatremia. Patients ranged in age from 8 to179 days, and
      body weight ranged from 3 to 4.12 kg. Mean sodium concentration increased from
      130.17 +/- 1.94 mEq/L to 133.67 +/- 3.88 mEq/L (p=0.048), and median urine output
      increased from 4.15 to 5.05 mL/kg/hr (p=0.286). No significant changes were noted
      in serum potassium, bicarbonate, creatinine, or BUN. No adverse effects were
      noted during conivaptan infusion. CONCLUSION: Intravenous conivaptan is effective
      for increasing serum sodium levels and may be a potential adjuvant to enhance
      diuresis in children with cardiac disease. Given the potential benefits of
      conivaptan compared to diuretic therapy, with all their potential complications,
      prospective trials are warranted.

PMID- 23118661
TI  - Decrease in therapeutic errors involving prescription cough and cold medications
      in young children.
AB  - OBJECTIVES: This study sought to determine whether an increase in therapeutic
      errors involving prescription cough and cold medications (CCM) reported to poison
      centers was observed following the October 2007 voluntary withdrawal of over-the
      counter CCM. METHODS: Analysis of therapeutic errors involving prescription CCM
      in children under 2 years of age for the 33 months before and the 27 months after
      the October 2007 withdrawal. RESULTS: Total counts of therapeutic errors
      involving prescription CCM in children under 2 years of age decreased from 452 to
      337 per year. Rates of therapeutic errors decreased from 0.43 cases/100,000
      person-month prewithdrawal to 0.32 postwithdrawal, a 25.6% decrease (p<0.0001).
      CONCLUSIONS: An increase in harm as measured by the number of poison center calls
      for therapeutic errors involving prescription CCM was not observed in the 27
      month time period after the withdrawal. A significant decrease in therapeutic
      errors involving these products is reported.

PMID- 23118662
TI  - Management of patients with cystic fibrosis and allergic bronchopulmonary
      aspergillosis using anti-immunoglobulin e therapy (omalizumab).
AB  - Omalizumab is a recombinant DNA-derived humanized immunoglobulin G (IgG) anti-IgE
      monoclonal antibody approved for use in patients with allergic asthma. However,
      it is not approved for allergic bronchopulmonary aspergillosis (ABPA).
      Conflicting reports exist about the effects of omalizumab on ABPA in patients
      with cystic fibrosis (CF). We report 2 patients with CF treated with omalizumab,
      in whom frequency of ABPA exacerbations was markedly reduced with treatment.
      Additionally, hospitalizations were reduced from 5 per year to once in 18 months
      in the first patient and from twice to once per year in the second patient. Free
      IgE decreased by 87.9% after 6 months of therapy in the first patient and by
      95.6% after 7 months of therapy in the second patient. Neither of the two
      patients had evidence of asthma. Omalizumab may be useful in treating ABPA in
      patients with CF, and including free IgE in monitoring the response to therapy
      will be helpful.

PMID- 23118663
TI  - Probable association of tachyarrhythmia with nebulized albuterol in a child with
      previously subclinical wolff Parkinson white syndrome.
AB  - We present the case of a 2-year-old asthmatic boy with atrioventricular (AV)
      reentry tachycardia following albuterol inhalation, who was later diagnosed with
      Wolff-Parkinson-White (WPW) syndrome. The Naranjo adverse drug reaction
      probability scale score for this adverse event was 7, indicating that the
      association between his AV-reentry tachycardia and inhalation of albuterol is
      probable. To our knowledge, this is the first case report that shows the
      potential arrhythmogenic effects of albuterol in a child with WPW syndrome. We
      urge clinicians to be aware of this potentially life-threatening adverse effect
      and to closely monitor these patients when they need beta-adrenergic drugs in
      case of emergency. Furthermore, this report highlights the dilemma regarding the
      safe treatment of pediatric patients with both asthma and WPW syndrome.

PMID- 23118664
TI  - Injectable ammonium chloride used enterally for the treatment of persistent
      metabolic alkalosis in three pediatric patients.
AB  - Enteral administration of injectable ammonium chloride may offer an effective
      method for the treatment of persistent metabolic alkalosis, without the adverse
      effects associated with the intravenous route. This case series describes 3
      pediatric patients who received ammonium chloride enterally for the treatment of
      persistent metabolic alkalosis. The patients were a 2-month-old female infant, a
      6-week-old male infant, and a 3-year-old male toddler. Four to 18 doses of
      ammonium chloride were administered enterally (range, 3-144 mEq/dose). Two of the
      3 patients achieved resolution of metabolic alkalosis with ammonium chloride,
      while 1 patient's condition was refractory to treatment. Resolution of metabolic
      alkalosis occurred at 4 and 8 days, which required a total weight-based dose of
      10.7 mEq/kg and 18 mEq/kg, respectively. No adverse effects were recorded. The
      use of ammonium chloride injection administered enterally was a safe and
      effective option in 2 of the 3 pediatric patients with persistent metabolic
      alkalosis.

PMID- 23118665
TI  - Pro-con debate: etomidate or ketamine for rapid sequence intubation in pediatric
      patients.
AB  - When caring for critically ill children, airway management remains a primary
      determinant of the eventual outcome. Airway control with endotracheal intubation
      is frequently necessary. Rapid sequence intubation (RSI) is generally used in
      emergency airway management to protect the airway from passive regurgitation of
      gastric contents. Along with a rapid acting neuromuscular blocking agent,
      sedation is an essential element of RSI. A significant safety concern regarding
      sedatives is the risk of hypotension and cardiovascular collapse, especially in
      critically ill patients or those with pre-existing comorbid conditions. Ketamine
      and etomidate, both of which provide effective sedation with limited effects on
      hemodynamic function, have become increasingly popular as induction agents for
      RSI. However, experience and clinical investigations have raised safety concerns
      associated with both etomidate and ketamine. Using a pro-con debate style, the
      following manuscript discusses the use of ketamine versus etomidate in RSI.

PMID- 23118666
TI  - Feasibility of short-term infusion of magnesium sulfate in pediatric patients
      with status asthmaticus.
AB  - OBJECTIVE: This report describes the feasibility of high-dose magnesium sulfate
      infusion in pediatric patients with status asthmaticus. METHODS: Retrospective
      chart review over a 3-year period of all patients younger than 18 years of age
      with status asthmaticus who underwent a high-dose magnesium sulfate infusion for
      4 hours. All patients were breathing spontaneously but were refractory to
      conventional therapy. The magnesium sulfate infusion regimen was 50 mg/kg (for
      patients weighing >30 kg) or 75 mg/kg (for those weighing <=30 kg) over a period
      of 30 to 45 minutes, followed by a continuous infusion of 40 mg/kg/hr for 4
      hours. Information regarding vital and clinical respiratory signs, serum
      magnesium (SrMg), ionized magnesium (iMg), electrocardiograms, and cardiac
      troponin levels were retrieved. We analyzed the relationship between SrMg and iMg
      by using linear regression analysis. RESULTS: Nineteen patients were included. At
      the end of the infusion, SrMg levels were 4.4 +/- 0.8 mg/dL, and iMg levels were
      0.95 +/- 0.2 mmol/L. SrMg levels only moderately predicted iMg (r(2) = 0.541).
      There were no reports of hypotension, respiratory failure, neurological problems,
      or nausea. Discomfort at the site of infusion was reported in three cases.
      Troponin levels (n = 12) and electrocardiograms (n = 12), when available, were
      noted at the end of the infusion and were normal in all patients p=0.01.
      CONCLUSIONS: In this case series, short-term high-dose administration of
      magnesium sulfate in the context of status asthmaticus was feasible, and we did
      not observe clinical complications with its use. Total SrMg was inadequate to
      reflect the active form of magnesium, iMg. The dose used achieved theoretical
      therapeutic levels of iMg.

PMID- 23118667
TI  - The development of evidence-based care recommendations to improve the safe use of
      anticoagulants in children.
AB  - Evidence-based care recommendations and standardized protocols improve outcomes.
      In addition, anticoagulant management has been recognized by The Joint Commission
      (TJC) as an opportunity for improving patient safety. A National Patient Safety
      Goal requiring a standardized process for patients receiving anticoagulants was
      established by TJC. This requirement provided an opportunity to apply evidence
      based care recommendations to the issue of safe anticoagulant use. To meet TJC
      requirement, the following searchable clinical question was drafted: "In children
      receiving anticoagulation therapy, what are the appropriate dosing, laboratory
      monitoring, timing, and dosing adjustments for warfarin, unfractionated heparin,
      and low-molecular-weight heparin to prevent coagulation-related complications?"
      The team used the Appraisal of Guidelines Research and Evaluation Collaboration
      (AGREE) instrument to evaluate the quality and relevance of identified guidelines
      in answering the clinical question. Best Evidence Statements (BESts) were
      developed for each of the medications (warfarin, low-molecular-weight heparin,
      and unfractionated heparin). BESts provide the format for the presentation of
      recommendations, discussion, and methods for point-of-care providers seeking
      synthesized evidence to guide care decisions. The primary goal of developing and
      implementing these statements was to standardize the use of anticoagulants and to
      prevent unsafe practices. A secondary goal was to ensure accessibility of the
      BESts throughout our organization, including the electronic medical record,
      various internal division home pages, and our organization's external website.
      The anticoagulant BESts developed at our organization show how an
      interprofessional approach to patient care results in the development of evidence
      based care recommendations. The BESts were developed to standardize care
      associated with the use of anticoagulants and to provide dosing and monitoring
      parameters to ensure safe care to all patients receiving these medications. The
      development of evidence-based care recommendations can be accomplished with a
      focused interprofessional team dedicated to providing the safest possible care to
      patients.

PMID- 23118668
TI  - Inappropriate vancomycin therapeutic drug monitoring in hospitalized pediatric
      patients increases pediatric trauma and hospital costs.
AB  - OBJECTIVES: The objective of this study was to measure the appropriateness of
      vancomycin monitoring in a pediatric tertiary care center and to evaluate the
      effectiveness of two interventions, autonomous pharmacy therapeutic drug
      monitoring and health care provider education, in reducing avoidable pediatric
      patient trauma and hospital cost. METHODS: A retrospective chart review
      evaluating vancomycin therapeutic drug monitoring (TDM) in pediatric inpatients
      was performed before and after the introduction of an autonomous pharmacy TDM
      program and health care provider (HCP) education. RESULTS: Thirty-five patients
      were included in our study, prior to any intervention. Of these, 9% of patients
      had trough concentrations appropriately deferred. Of the total of 64 trough
      concentrations obtained, 94% were considered to be inappropriate. After the start
      of the autonomous pharmacy TDM program, of the 54 eligible patients (111
      troughs), 9% had trough concentrations appropriately deferred, and 34% were
      inappropriate. In the 3-month period following the introduction of HCP education
      in combination with pharmacy TDM, we identified 27 eligible patients. Among
      those, 15% of the patients had trough concentrations appropriately deferred. Of
      the 43 trough concentrations obtained, only 9% were considered to be
      inappropriate. The combination of pharmacy TDM with HCP education decreased
      annualized hospital cost by 60%, from $13,080 to $5232. CONCLUSIONS:
      Inappropriate vancomycin TDM occurs commonly in our institution, resulting in
      unnecessary hospital cost and patient trauma. The combination of pharmacy TDM and
      HCP education significantly improved clinical practice; however, results were
      short-lived. Further interventions, such as computer based order entry, will
      likely be needed to reinforce and improve long-term TDM practice in pediatric
      patients.

PMID- 23118669
TI  - Implementation of a standardized process for ordering and dispensing of high
      alert emergency medication infusions.
AB  - OBJECTIVES: Pharmacies encounter challenges when ensuring safe, timely medication
      dispensing to patients in the pediatric intensive care unit, when high-alert
      medications are needed in emergent situations. Removal of these medications from
      nursing stock presented challenges to providing timely administration to critical
      patients. The project's purpose was to develop a new method for reducing
      dispensing time while improving patient safety in pediatric intensive care units.
      METHODS: A committee of physicians, nurses, a clinical pharmacist, and pharmacy
      administration collaborated for process development. The process established a
      list of compounded, ready-to-use infusions stored in the pharmacy, immediately
      available for dispensing. The dispensing mechanism includes ordering and
      dispensing processes using an "Urgent Drip Request" form. Most frequently ordered
      infusions (dopamine, epinephrine, norepinephrine) were added to automated
      dispensing cabinets in critical care units in concentrations that could be safely
      infused centrally or peripherally. RESULTS: During the initial 4 months, 71
      "Urgent Drip Request" sheets were processed. Drug utilization evaluation
      demonstrated a dispensing time of less than 1 minute for drip medications leaving
      the pharmacy after the form was received. No sheets processed exceeded the
      institutional 30-minute turnaround time, nor were errors or delays documented.
      Limited turnaround time data existed preimplementation but was not robust enough
      for analysis. It was not ethically feasible to perform a head-to-head comparison
      with the previous method, as it might have resulted in delay of therapy and
      negative patient outcomes. CONCLUSIONS: This program allows high-alert medication
      infusion availability in an expedited manner, removes potential for compounding
      errors at the bedside, and assures clean room preparation. This has improved
      pharmacy efficiency in provision of safe patient care to critically ill pediatric
      patients.

PMID- 23118670
TI  - The pharmacokinetics of oseltamivir and oseltamivir carboxylate in a critically
      ill pediatric patient receiving extracorporeal membrane oxygenation and
      continuous venovenous hemodialysis.
AB  - This report details the pharmacokinetics of oseltamivir and oseltamivir
      carboxylate following administration of high-dose oseltamivir in a critically ill
      child receiving extracorporeal membrane oxygenation (ECMO) and continuous
      venovenous hemodialysis (CVVHD). A 6-year-old critically ill male patient
      suffering from a presumed viral illness was transferred to our institution's
      pediatric intensive care unit from an outside hospital after developing
      respiratory failure and cardiomegaly. ECMO and oseltamivir therapy were initiated
      upon admission, and CVVHD was started on hospital day 3. Pharmacokinetic sampling
      occurred at an oseltamivir dose of approximately 4 mg/kg on hospital day 6. The
      patient's oseltamivir and oseltamivir carboxylate area under the plasma
      concentration time curves for the 12-hour dosing interval (AUC(0-12)) were 30.5
      and 905 ng/mLhr, respectively. Drug clearance by CVVHD was 31.6 mL/min for
      oseltamivir and 26.9 mL/min for oseltamivir carboxylate. Pre- and postoxygenator
      oseltamivir and oseltamivir carboxylate plasma concentrations did not differ
      substantially. The patient's oseltamivir carboxylate plasma concentrations
      remained well above the reported mean 50% inhibitory concentration for 2009
      pandemic H1N1 virus. However, despite receiving twice the standard dose of
      oseltamivir, the oseltamivir carboxylate AUC(0-12) in our patient was less than
      that reported in noncritically ill pediatric subjects. The reduced oseltamivir
      carboxylate AUC(0-12) found in our patient was most likely due to decreased drug
      absorption.

PMID- 23118671
TI  - Acute intoxication caused by a synthetic cannabinoid in two adolescents.
AB  - Illicit drug use continues to be a common problem among pediatric patients. Daily
      marijuana use among high school seniors is currently at a 30-year high. Marijuana
      use in adults has rarely been associated with cardiovascular adverse effects,
      including hypertension, tachycardia, arrhythmia, and myocardial infarction.
      Recently, abuse of synthetic cannabinoids, such as the incense "K2" or "Spice,"
      has been increasingly reported in the lay press and medical literature. Overdose
      and chronic use of these substances may cause adverse effects including altered
      mental status, tachycardia, and loss of consciousness. Overdoses in adult
      patients have been described; however, limited reports in the pediatric
      population have been documented. A recent case series describes myocardial
      infarctions in pediatric patients, associated with synthetic cannabinoid use. In
      this report, we describe two adolescent patients admitted after they inhaled
      "K2," resulting in loss of consciousness, tachycardia, and diffuse pain.

PMID- 23118674
TI  - PPAG 2012 Board Election Results.

PMID- 23118675
TI  - 2012 PPAG Fellows.

PMID- 23118673
TI  - Hepatotoxicity after continuous amiodarone infusion in a postoperative cardiac
      infant.
AB  - A former 34-week-old female infant with Down syndrome underwent surgical
      correction of a congenital heart defect at 5 months of age. Her postoperative
      course was complicated by severe pulmonary hypertension and junctional ectopic
      tachycardia. Following treatment with amiodarone infusion, she developed
      laboratory indices of acute liver injury. At their peak, liver transaminase
      levels were 19 to 35 times greater than the upper limit of normal. Transaminitis
      was accompanied by coagulopathy, hyperammonemia, and high serum lactate and lipid
      levels. Hepatic laboratory abnormalities began to resolve within 48 hr of
      stopping amiodarone infusion. Heart rate control was achieved concurrently with
      discovery of laboratory test result abnormalities, and no further antiarrhythmic
      therapy was required. The intravenous formulation of amiodarone contains the
      diluent polysorbate 80, which may have hepatotoxic effects. Specifically, animal
      studies suggest that polysorbate 80 may destabilize cell membranes and predispose
      to fatty change within liver architecture. Polysorbate was implicated in infant
      fatalities from E-ferol use in the 1980s. This case illustrates a possible
      adverse event by the Naranjo probability scale. Given the extent of clinically
      apparent hepatic injury, this patient was not rechallenged with amiodarone during
      the remainder of her hospitalization. With amiodarone now used as first-line
      pharmacologic therapy for critical tachyarrhythmia in this population, the number
      of children exposed to this drug should be expected to increase. Laboratory
      indices of liver function should be evaluated at initiation of amiodarone
      therapy, as well as frequently throughout duration of therapy. Consideration
      should be given to polysorbate-free formulation of intravenous amiodarone for use
      in the cohort with congenital cardiac disease.

PMID- 23118672
TI  - Chloramphenicol toxicity revisited: a 12-year-old patient with a brain abscess.
AB  - Chloramphenicol, a broad-spectrum antibiotic, is rarely used in the United States
      due to its well-described adverse effects. Because of its limited use, many
      clinicians are unfamiliar with its indications, spectrum of activity, and
      potential adverse drug effects. We describe a 12-year-old patient who presented
      after two craniotomies for a persistent brain abscess complicated by long-term
      chloramphenicol administration. Findings for this patient were consistent with
      many of the adverse drug effects associated with chloramphenicol, including
      elevated chloramphenicol serum concentrations, anemia, thrombocytopenia,
      reticulocytopenia, and severe metabolic acidosis. Rare manifestations of
      chloramphenicol toxicity that developed in this patient included neutropenia,
      visual field changes, and peripheral neuropathy. Chloramphenicol administration
      was discontinued, and hemodialysis was initiated for severe metabolic acidosis.
      The patient recovered with severe visual field deficits. Although chloramphenicol
      is rarely indicated, it remains an effective antibiotic. Healthcare providers
      should become familiar with the pharmacology, toxicology, and monitoring
      parameters for appropriate use of this antibiotic.

PMID- 23118676
TI  - Has the 'therapeutic orphan' finally been adopted?

PMID- 23118677
TI  - Selective serotonin reuptake inhibitors for the treatment of obsessive-compulsive
      disorder in children and adolescents.
AB  - The introduction of the selective serotonin reuptake inhibitors (SSRIs) has been
      a major advance in pediatric psychiatry, while contemporary advances in the
      understanding of obsessive-compulsive disorder (OCD) phenomenon in children have
      facilitated its identification and treatment. Currently, fluvoxamine and
      sertraline are the only SSRIs that have received FDA approval for the treatment
      of childhood OCD. The purpose of this article is to review the safety and
      efficacy of SSRIs in the treatment of obsessive-compulsive disorder (OCD) in
      children and adolescents.

PMID- 23118678
TI  - Measles-mumps-rubella vaccine and the development of autism or inflammatory bowel
      disease: the controversy should end.
AB  - Vaccines have been administered to millions of individuals, usually infants and
      children, with few serious adverse effects. In 1998 a report suggested that there
      may be a link between the measles-mumps-rubella vaccine and the development of
      behavioral abnormalities (i.e., autism) and inflammatory bowel disease in
      children. This report generated considerable media and political attention, which
      many feared would result in a decreased willingness of parents to immunize their
      children against these contagious diseases. Over the past decade, an increasing
      number of healthcare practitioners have been credentialed to administer
      vaccinations. Therefore, it is imperative for all medical professionals to
      understand the controversy surrounding this issue and to be able to appropriately
      educate and advise parents accordingly. This review article evaluated the primary
      and secondary literature pertaining to this topic and concluded that the
      available epidemiological and scientific evidence does not support a causal
      association between the MMR vaccine and autism or inflammatory bowel disease.

PMID- 23118679
TI  - Appropriateness of anticonvulsant concentration monitoring in hospitalized
      pediatric patients.
AB  - OBJECTIVES: We assessed the appropriateness of anticonvulsant concentration
      monitoring in hospitalized pediatric patients admitted to a teaching hospital.
      METHODS: Literature-based criteria for anticonvulsant concentration monitoring
      were approved by the Pharmacokinetic and Neurology Services of Le Bonheur
      Children's Medical Center. A random sample of anticonvulsant concentrations
      ordered over a 6 month period was assessed. Patient demographics, anticonvulsant
      data, the type of professional who recommended the concentration, and sampling
      time were collected concurrent with hospitalization. Concentrations were assessed
      for appropriateness of indication and sampling time. RESULTS: Concentrations
      (n=141) were obtained in 74 patients (mean age = 6.5+5.5 years) admitted to the
      floor (86%) or ICU (14%). Length of stay was 8.3+16.9 days. Monotherapy was used
      in 78.3% of patients. Carbamazepine (28.4%), phenytoin (27.5%), phenobarbital
      (27.6%), valproate (14.8%) or free phenytoin (1.7%) concentrations were
      recommended by a pediatrician (70.5%), neurologist (21.5%), neurosurgeon (2.1%),
      or Pharmacokinetic Services (5.9%). Fifty-three percent of all concentrations met
      appropriateness criteria for indication; however, 8.5% of tests were collected
      incorrectly. About half of the concentrations recommended by pediatricians
      (47.5%), neurologists (43.3%), and neurosurgeons (66.7%) did not meet
      appropriateness criteria for indication. The main reasons for inappropriate
      anticonvulsant concentration monitoring include frequent repetitive sampling (<24
      hours), obtaining an anticonvulsant concentration without an appropriate
      indication, failure to correctly apply the concept of pharmacological steady
      state, incorrect identification of drug-drug interactions, and sampling
      irrespective of dosing schedule. CONCLUSIONS: One-half of all anticonvulsant
      concentrations fulfilled the indication criteria. There was no difference in
      appropriateness of indication based on the service recommending the concentration
      or for each specific anticonvulsant. The appropriateness rates reported are
      comparable to those reported in other studies. Inappropriate anticonvulsant
      concentration monitoring fails to improve patient care and contributes to a
      significant waste of financial resources.

PMID- 23118680
TI  - Self-administration at school of prescribed medications for asthma and
      anaphylaxis.

PMID- 23118681
TI  - Review and update of insulin dependent diabetes mellitus.
AB  - The purpose of this article is to provide the health care practitioner with a
      comprehensive review of the pathophysiology and treatment of Type 1 Diabetes
      Mellitus. Traditionally, insulin has been administered via an insulin syringe. In
      the recent past, diabetes research has focused on developing more convenient
      insulin delivery devices and longer acting insulin's in hopes of increasing
      compliance with insulin therapy and improving the management of Type 1 diabetes
      in both children and adults. Rapidly developing approaches to insulin delivery
      for Type 1 diabetes continue to be developed at a rapid rate, including
      administration via continuous subcutaneous insulin infusion in addition to other
      new approaches. With these advances in therapy, pediatric patients with Type 1
      diabetes have been able to achieve strict glycemic control, although the
      treatment of hypoglycemia remains a burden. The objectives of this article are to
      the following: to review the epidemiology, risk factors, pathophysiology,
      clinical manifestations, and diagnostic criteria of Type 1 diabetes mellitus in
      children,; to discuss the management of these patients, including, insulin
      therapy, monitoring, diet and exercise, carbohydrate counting and treatment of
      hypoglycemia,; and to review insulin administration devices, including insulin
      pens, insulin jet injectors, insulin pumps, and novel insulin delivery systems.

PMID- 23118682
TI  - Systematic steps to diminish multi-fold medication errors in neonates.
AB  - Tenfold and other multiple-of-dose errors are particularly common in the neonatal
      intensive care unit (NICU), where the fragility of the patients increases the
      potential for significant adverse outcomes. Such errors can originate at any of
      the sequential phases of the process, from medication ordering to administration.
      Each step of calculation, prescription writing, transcription, dose preparation,
      and administration is an opportunity for generating and preventing medication
      errors. A few simple principles and practical tips aimed at avoiding decimal and
      other multiple-dosing errors can be systematically implemented through the
      various steps of the process. The authors describe their experience with the
      implementation of techniques for error reduction in a NICU setting. The
      techniques described herein rely on simple, inexpensive technologies for
      information and automation, and on standardization and simplification of
      processes. They can be immediately adapted and applied in virtually any NICU and
      could be integrated into the development of computerized order entry systems
      appropriate to NICU settings. Either way, they should decrease the likelihood of
      undetected human error.

PMID- 23118683
TI  - An Evaluation of Gentamicin, Tobramycin, and Amikacin
      Pharmacokinetic/Pharmacodynamic Parameters in HIV-Infected Children.
AB  - BACKGROUND: The purpose of the study was to calculate gentamicin, tobramycin, and
      amikacin pharmacokinetic parameters in HIV-infected children and compare
      conventional multiple daily aminoglycoside dosing to once-daily aminoglycoside
      (ODA) dosing in attaining peak serum aminoglycoside concentrations (SACs) to
      minimum inhibitory concentration for 90% of isolates (MIC(90)) ratios >=8 against
      selected pathogens. METHODS: Patients (<13yrs) receiving an aminoglycoside (15
      patients/drug) in the treatment of gram-negative infection were studied.
      Intravenous gentamicin/ tobramycin were administered at a dose of 6-7.5 mg/kg/day
      and amikacin at 20-30 mg/kg/d divided every 8 hrs. Peak and trough serum
      concentrations were obtained and pharmacokinetic parameters were calculated
      utilizing a one-compartment steady-state model. SACs for gentamicin/tobramycin
      dosed at 7.5 mg/kg and amikacin at 22.5 mg/kg once daily were simulated using the
      calculated pharmacokinetic parameters. Peak SAC:MIC(90) ratios were calculated
      for each dosing method. RESULTS: Mean pharmacokinetic parameters were within 1
      standard deviation of reported literature values. Mean peak:MIC(90) ratio of >=8
      was attained only for Klebsiella species (MIC90 1 MUg/mL) using conventional
      gentamicin/tobramycin dosing whereas mean amikacin peak:MIC(90) ratios >=8 were
      reached for Klebsiella, Enterobacter, and Citrobacter species (MIC(90) 4 MUg/mL).
      ODA simulations predicted gentamicin/tobramycin peak:MIC(90) ratios >=8 in 100%
      of patients with an organism-MIC(90) of 1 MUcg/mL and in 80% of patients with an
      organism-MIC(90) of 2 MUg/mL. Amikacin peak:MIC(90) ratio >=8 was predicted for
      93% of patients with an organism-MIC(90) of 4 MUg/mL but in only 27% if the
      MIC(90) was 8 MUg / mL. CONCLUSION: Optimal peak SAC:MIC90 ratios using
      conventional aminoglycoside dosing were predicted only for organisms with low
      MIC(90) values. ODA dosing represents an option for improving pharmacodynamic
      outcomes.

PMID- 23118684
TI  - Treatment of acute rheumatic carditis with choline magnesium trisalicylate in a
      patient needing surgery.
AB  - Acute rheumatic fever is a post-infectious illness characterized by diffuse
      inflammation. Typically, high-dose anti-inflammatory agents are used as primary
      therapy for this disorder. In addition to their anti-inflammatory properties,
      these agents, most frequently aspirin, also have anti-platelet properties. We
      describe the case of an 11-year-old patient with rheumatic fever who needed to
      undergo surgery. The use of traditional anti-inflammatory agents would have posed
      a potential problem with post-surgical bleeding, so a lesser-used anti
      inflammatory agent (i.e., choline magnesium trisalicylate) was selected.

PMID- 23118685
TI  - Metabolic acidosis in a pediatric patient receiving topiramate.
AB  - Topiramate is an anticonvulsant that is labeled for the management of several
      seizure types in children >2 years of age. With the exception of cognitive
      dysfunction, nephrolithiasis, weight loss, and paresthesia, adverse effects in
      children are similar to other those noted with other anticonvulsants. We describe
      a 33-month-old child with complex partial seizures and secondary generalization
      who received topiramate 45 mg orally twice daily (6.2 mg/kg/d) for approximately
      4 weeks before admission. He developed asymptomatic metabolic acidosis that was
      evidenced by a decrease in HCO(3) (-), which was unresponsive to treatment with
      sodium bicarbonate. The child was weaned off topiramate and the metabolic
      acidosis resolved 48 hours after its discontinuation.

PMID- 23118686
TI  - Managing asthma: past, present, and future.
AB  - Asthma has been recognized in the medical literature for almost 2000 years.
      Modern pharmaco-therapy for asthma began with the commencement of the 20(th)
      century following the development of epinephrine and the demonstration of its
      effectiveness for acute symptoms of asthma. Progressive development of this class
      of bronchodilator medication has provided greater beta2 specificity and longer
      duration of action. Corticosteroids were introduced about 50 years ago. As a
      systemic medication, they provided anti-inflammatory activity that continues to
      be essential for exacerbations of symptoms that are unresponsive to a
      bronchodilator. Corticosteroids were subsequently developed as inhaled agents for
      long-term maintenance therapy. The availability of corticosteroids with high
      topical effect has permitted the use of smaller doses with minimal systemic
      effect; therefore, the inhaled corticosteroids have become the most effective
      monotherapeutic agents for chronic asthma.Both theophylline and long-acting beta2
      agonists (e.g., salmeterol) provide additive clinical effect to small doses of
      inhaled corticosteroids. This effect is greater than that achieved with larger
      doses of the inhaled steroid used alone. A new approach to managing allergic
      asthma is now available in the form of a monoclonal antibody directed against
      immunoglobulin E (IgE). This agent, omalizumab, binds to circulating IgE, thereby
      preventing IgE from binding to mast cells. This subsequently prevents the release
      of mediators for bronchospasm and inflammation. Under investigation are
      monoclonal antibodies to modify the effects of interleukins involved in the
      inflammatory process of asthma. Phosphodiesterase inhibitors that are more
      specific than theophylline and monoclonal antibodies that prevent the attachment
      of rhinovirus to respiratory mucosa are being studied. Since rhinoviruses are
      major causes of acute exacerbations of asthma, these and other measures to
      prevent or modify the common cold provide great potential for further improvement
      in the outcome of asthma.

PMID- 23118687
TI  - Type 2 diabetes mellitus in children and adolescents: the new challenge.
AB  - The epidemic increase in the incidence of type 2 diabetes mellitus (T2DM) in
      children and adolescents is presenting enormous challenges to the medical
      profession. The combination of factors such as obesity, ethnicity, puberty, and
      genetic predisposition has contributed to the development of T2DM in younger
      ages. These factors affect the regulatory mechanism of insulin secretion, insulin
      action, and hepatic gluconeogenesis. In contrast to adults, children appear to
      have a shorter latency to disease, a more rapid development of symptoms, and an
      increased ketoacidosis. There are limited therapeutic options to prevent or
      manage T2DM in children. Although the role of diet and exercise (lifestyle
      intervention) has not been adequately evaluated in children, they will remain
      important adjuncts in the prevention and treatment of T2DM. Insulin and metformin
      are currently the only approved medications for the treatment of T2DM in
      children. Clinical trials involving other oral agents used in adults are
      currently being conducted to evaluate their safety and efficacy in children.

PMID- 23118688
TI  - The role of pamidronate in pediatric patients with severe osteogenesis
      imperfecta.
AB  - Osteogenesis imperfecta (OI) is a heritable bone disorder with clinical features
      that include bone fragility, blue sclerae, and short stature. There are four main
      subtypes of OI, encompassing a wide range of clinical severity. The majority of
      patients have mutations in either the COL1A1 or COL1A2 gene that ultimately lead
      to an abnormal synthesis of or a decrease in the production of collagen.
      Bisphosphonates have been used effectively in adults and children to treat other
      bone disorders, since they have been proven to increase bone density through
      inhibition of bone resorption. Recent studies have demonstrated the advantages of
      pamidronate therapy in the treatment of children and adolescents with the more
      severe forms of OI. Pamidronate consistently increases bone mass, vertebral
      growth, and quality-of-life while decreasing the number of fractures in children
      with severe OI. Long-term effects are promising, and benefits of pamidronate
      therapy appear to outweigh the possible risks.

PMID- 23118689
TI  - Intraventricular vancomycin in pediatric patients with cerebrospinal fluid shunt
      infections.
AB  - OBJECTIVES: TO DETERMINE: 1) the range and magnitude of vancomycin trough
      cerebrospinal fluid (CSF) concentrations following intraventricular (IVT)
      vancomycin; 2) any correlation between patient demographic and CSF vancomycin
      concentrations; and 3) eradication and complications rates following IVT
      vancomycin. METHODS: Medical records of pediatric patients with shunt infection
      who received IVT vancomycin during a 12 month period were reviewed. Demographic,
      microbiological data, IVT/intravenous (IV) vancomycin dosing, concomitant
      antibiotics, CSF and serum vancomycin concentrations, and CSF drainage output
      were recorded. RESULTS: Seventeen patients ages 4 months to 17 years were
      hospitalized for shunt infection. Staphylococcus epidermidis (n=12) was the
      predominant organism. Sixteen patients received 10 mg, and one patient received 5
      mg of IVT vancomycin for 3-23 days. All but one received concurrent IV
      vancomycin. The mean maximum trough CSF vancomycin concentration noted for 16
      patients who recieved 10 mg of IVT vancomycin was 18.4+/-21.8 MUg/mL (range:
      between 0.4 to 187.3 MUg/mL). All four adolescents >=25 kg had CSF vancomycin
      concentrations <=5 MUg/mL, three of four infants/children between 10.1 and 24.9
      kg had trough CSF vancomycin concentrations between 10-20 MUg/mL, and five of
      nine infants <10 kg had CSF concentrations >20 MUg/mL. All organisms were
      successfully eradicated. One patient developed chronic eosinophilia presumed
      related to elevated CSF vancomycin concentrations (187 MUg/mL).  CONCLUSIONS
      #ENTITYSTARTX02013;: The combination of IVT and IV vancomycin effectively
      eradicated CSF shunt infections. CSF vancomycin concentrations are highly
      variable and poorly correlated with age and CSF output. Following a 10 mg IVT
      vancomycin dose, CSF concentrations appear to be lower in older children and
      elevated in infants/young children. One infant experienced a complication related
      to an elevated CSF vancomycin concentration; hence, therapy must be
      individualized, using CSF trough vancomycin concentrations.

PMID- 23118690
TI  - Plasma Concentrations Following Application of Whole versus Cut Transdermal
      Clonidine Patches To Critically Ill Children.
AB  - Clonidine is used for hypertension and narcotic withdrawal prophylaxis in adults
      and children. This study described plasma absorption of clonidine from whole and
      cut transdermal clonidine patches. This was a retrospective descriptive study in
      an 18 bed multidisciplinary pediatric intensive care unit, evaluating 15
      critically ill children with a median age of 1.1 years (range 0.3-11 years)
      treated with transdermal clonidine for narcotic withdrawal prophylaxis, and who
      had plasma clonidine concentrations measured. An assessment of the relationship
      between clonidine dose and patch integrity (whole vs. cut) with plasma
      concentrations was performed, with further analysis by Spearman Correlation
      Coefficient. Clonidine doses averaged 7.5+/-4.2 MUg/kg/day (range 2.3-20
      MUg/kg/day) for 9.8+/-4.3 days (range 4-20 days). There were 9 cut patches and 6
      whole patches. The average prescribed dose delivered by cut patches was 6.4+/-3
      MUg/kg/day, resulting in a mean plasma concentration of 1+/-1.1 ng/ mL (range
      <0.05-3.3 ng/mL). The average prescribed dose delivered by whole patches was 7+/
      1.7 MUg/kg/day, resulting in a mean plasma concentration of 0.55+/-0.3 ng/mL
      (range 0.13-1.5 ng/mL). The Spearman Correlation Coefficient was calculated to
      evaluate the correlation between dose and concentration. For whole and cut
      patches the correlation coefficient was 0.94 (P=0.005) and 0.72 (P=0.002),
      respectively. Doses ranging from 1.7 to 20 MUg/kg/day using whole patches
      resulted in no plasma concentrations >2 ng/mL. However, a plasma concentration >2
      ng/mL was achieved with a dose of 8.8 MUg/kg/day delivered by a cut patch. In
      addition, the 2 samples that resulted in undetectable concentrations were taken
      from patients who were treated with cut patches. The results from this pilot
      study suggest that critically ill children absorb clonidine from transdermal
      patches, but the rate and extent of absorption appears to be more predictable
      with the use of whole patches compared to patches that have been cut.

PMID- 23118691
TI  - Methemoglobinemia associated with metoclopramide therapy in a neonate.
AB  - With the removal of cisapride from the U.S. market, practitioners have
      increasingly used other medications, such as metoclopramide, to treat
      gastroesophageal reflux in pediatric patients. We describe the case of a neonate
      who developed methemoglobinemia after receiving metoclopramide at doses slightly
      above the recommended age-appropriate dosage. Health care providers should be
      aware of this potentially serious side effect in young infants who receive this
      medication.

PMID- 23118692
TI  - Intraventricular tobramycin in a premature infant with pseudomonas meningitis.
AB  - A 38-week postconceptional age (29-week gestational age) infant required the
      placement of an Ommaya reservoir following a grade IV intraventricular hemorrhage
      and progressive hydrocephalus. At 70 days of age, a cerebrospinal fluid (CSF)
      culture was positive for Pseudomonas aeruginosa and the infant was empirically
      treated with age-appropriate parenteral doses of ceftazidime and gentamicin. This
      antibiotic regimen was changed to meropenem and tobramycin following the results
      of sensitivity reports. The infection failed to respond despite aggressive
      systemic dosing of antibiotics and removal of the Ommaya reservoir.
      Intraventricular injections of tobramycin were added to the systemic antibiotic
      regimen at a dose of 2 mg daily with subsequent doses adjusted to maintain trough
      concentrations in the CSF of 20-30 MUg/mL. The CSF was sterilized after three
      days of intraventricular injections. The infant completed seven days of
      intraventricular tobramycin plus a 24-day regimen of systemic antibiotics. No
      acute complications were noted with the addition of intraventricular injections.

PMID- 23118693
TI  - Clinical and Laboratory Issues in Community-acquired MRSA.
AB  - The prevalence of Methicillin-resistant Staphylococcus aureus (MRSA) has steadily
      increased over the past 40 years. Today, intravenous clindamycin or vancomycin is
      recommended for anti-staphylococcal coverage. Failure to identify resistant
      strains could result in the overuse of vancomycin and subsequent resistance to
      that antibiotic. Concerns over the emergence of this pathogen has caused many
      hospital laboratories to reassess their ability to identify antibiogram patterns
      and epidemiological shifts, determine appropriate laboratory testing, and review
      empiric therapy guidelines. Reliance on automated instrumentation to detect these
      isolates can result in major errors that cause false susceptible interpretations.
      The emergence of methicillin/oxacillin resistant strains has required additional
      laboratory analysis. This paper will review these tests and will focus on the
      role of the "D-test" in directing antibiotic therapy.

PMID- 23118694
TI  - Di(2-ethylhexyl)phthalate (DEHP).
AB  - Di(2-ethylhexyl) phthalate or DEHP is a colorless, oily liquid and notably, with
      respect to clinical concerns, is soluble in blood and body fluids containing
      lipoproteins. Despite being listed as a possible human carcinogen in the 1980's,
      more recent concerns have focused on its potential toxicity as a result of
      leaching from medical devices into patients via intravenous or enteral routes.
      Initial discussion of this problem was reported in the medical literature over 20
      years ago. This article provides an update on the status of DEHP as a potential
      reproductive toxin and the potential implications for high-risk population groups
      (most notably neonates). The use of the precautionary principle for a guidepost
      in relating human exposure effects to chemical agents, including DEHP, has become
      a topic relevant to all health care professionals and is discussed herein.

PMID- 23118695
TI  - Development of gastrointestinal function: risk factors for necrotizing
      enterocolitis.
AB  - The intestinal tract of the fetus matures rapidly in the third trimester of the
      pregnancy. The premature infant has decreased intestinal motility, limited
      digestion, absorption and excretion, and poor intestinal barrier defense. These
      limitations place the infant at high risk for acute intestinal injury,
      necrotizing enterocolitis. This article reviews the development of the
      gastrointestinal tract in the fetus, the barriers to feeding the high risk,
      premature infant, and the most serious intestinal disease, necrotizing
      enterocolitis.

PMID- 23118696
TI  - Influenza vaccination for the pediatric patient: a focus on the new intranasal,
      cold-adapted, live attenuated vaccine.
AB  - FluMist is the first live attenuated, cold-adapted intranasal influenza vaccine
      (LAIV) approved for the prevention of influenza A and B. Clinical trials have
      shown that annual vaccination with LAIV is effective for the prevention of
      influenza. LAIV appears well tolerated in healthy patients 5-49 years of age. The
      most common adverse events are abdominal pain, chills, cough, diarrhea, headache,
      irritability, lethargy, muscle aches, otitis media, rhinitis, sinusitis, sore
      throat, and vomiting. FluMist has a novel intranasal route of administration that
      allows for influenza prevention without a painful intramuscular injection.
      Barriers preventing acceptance of LAIV include defining the appropriate patient
      population, cost, and insurance coverage.

PMID- 23118697
TI  - Dietary supplement use in a pediatric inpatient population.
AB  - OBJECTIVES: Patients are assuming responsibility for their own health by self
      medicating with dietary supplements, often without physician knowledge or
      oversight. The objectives of this study were to determine: 1) pediatric dietary
      supplement use by surveying parents of children who were hospitalized in a
      university institution; 2) if any health care professional inquired about
      supplement use at the time the child was hospitalized; 3) whether the use of a
      supplement was documented in the patient's medical record; and 4) parents'
      attitudes about dietary supplements. STUDY DESIGN: Parents of 100 hospitalized
      pediatric patients (<18 years of age) were randomly selected to complete a survey
      about their child's use of dietary supplements prior to and during
      hospitalization. They were also asked if they intended to use these products
      after hospitalization. The purpose of the study was explained, informed consent
      was obtained, and parents were given ample time to complete the survey. RESULTS:
      Fifty percent of parents reported giving their child a dietary supplement prior
      to hospitalization; 17% reported use of an herbal supplement. Only 24% of parents
      reported being asked about supplement use by a health care professional upon
      admission or during the hospital stay. The response to only five of these queries
      was documented in the child's medical record. CONCLUSIONS: Increasing dietary
      supplement use mandates that all health care professionals elicit this
      information as part of the routine History and Physical Examination at the time a
      child is hospitalized. This information should also be documented in the
      patient's medical record. Likewise, parents should be encouraged to discuss the
      use of these products with their physician and pharmacist.

PMID- 23118698
TI  - A Cost Minimization Comparison of Two Surfactants-Beractant and Poractant alfa
      Based Upon Prospectively Designed, Comparative Clinical Trial Data.
AB  - OBJECTIVES: To compare the pharmacoeconomic profiles of beractant (Survanta((r)),
      Ross Laboratories, Columbus, Ohio) and poractant alfa (Curosurf((r)), DEY LP,
      Napa, CA) via a cost-minimization analysis. METHODS: This analysis was based upon
      clinical data from two previously published studies (Speer C, et al. Arch Dis
      Child 1995;72: F8-13; and Ramanathan R, et al. Am J Perinatol 2004; 21:109-19)
      where investigators found significant differences in the number of doses required
      to achieve a similar clinical response. Our analyses employed several models
      based upon single-use or multiple-use of single-use vial scenarios, average
      wholesale pricing, and costs computed on a per-patient basis. Model 1 involved
      single-dose vials and mean weight of the infants (both trials). Models 2 and 3,
      based on individual patient weights, assessed single-dose and multiple-use of
      single-dose vials cost scenarios, respectively. Individual patient weights
      allowed for statistical evaluation in Models 2 and 3. RESULTS: Model 1 savings
      with poractant alfa treatment was $949.67 (53%) based upon Speer and $617.90
      (46%) based upon Ramanathan. Models 2 and 3 reported savings for poractant alfa
      of $220.50 (20%) (P = 0.11) and $180 (20%) (P = 0.018), respectively over
      beractant. CONCLUSIONS: These analyses would suggest poractant alfa may offer a
      less costly, clinically-equivalent option. Savings may vary with vial usage and
      mix, patient weight distribution, and how surfactants are used in practice.
      Institutions utilizing surfactants may wish to examine usage patterns, dosing
      protocols, and patient mix to determine what potential savings may exist.

PMID- 23118699
TI  - Chemical compatibility of depacon((r)) with medications frequently administered
      by intravenous y-site delivery in patients with epilepsy or head trauma.
AB  - OBJECTIVES: Intravenous Y-site administration of more than one medication through
      the same in-line catheter is a common practice used in the management of acute
      seizures. The objective of this study was to determine the compatibility of
      valproate sodium (Depacon((r)); 2 or 20 mg/mL) with 13 medications that are
      frequently administered to manage seizures or are given to patients with an acute
      head injury who are at risk for developing post-traumatic epilepsy. METHODS: The
      study medications included atracurium, dexamethasone, diazepam, fosphenytoin,
      lorazepam, magnesium sulfate, mannitol, methyl-prednisolone, midazolam,
      pentobarbital, phenytoin, ranitidine, and thiopental. Equal volumes of valproate
      and each of the study drugs were admixed and immediately examined using several
      physiochemical criteria: Tyndall effect, color and pH change, gas evolution, and
      particle formation (HIAC/Royco liquid particle counter). Samples were also
      evaluated using HPLC analysis (C(18) column; methanol/tetrahydrofuran/ phosphate
      buffer; 44/1/55% v/v, at 1.5 mL/min; 50 degrees C) with UV (190-400 nm)
      photodiode detection. The valproate peak (220 nm) was quantified by both peak
      area and height. Samples were analyzed within 5 minutes of admixture and were
      reassessed at 15 and 30 minutes. RESULTS: With the exception of diazepam,
      midazolam, and phenytoin, all of the remaining drugs were chemically compatible
      with valproate, both in 5% Dextrose Injection, USP(D5W) and in 0.9% Sodium
      Chloride Injection, USP (Normal Saline -NS). None of the compatible medications
      produced a significant pH change, discernible gas, particle formation, reduced
      valproate titer by HPLC analysis (coefficient of variability < 1.5%), or the
      temporal formation of unidentified UV absorbing (190-400 nm) peaks. CONCLUSIONS:
      Intravenous valproate is compatible with most agents employed in seizure
      management or used in patients at risk for seizures following head injury and is
      safe for concurrent Y-site drug administration.

PMID- 23118700
TI  - Pediatric news.

PMID- 23118701
TI  - MDI versus Nebulizers for Acute Asthma.
AB  - OBJECTIVE: To evaluate studies comparing metered dose inhalers with holding
      chambers to nebulizers in the emergency department for the treatment of asthma
      exacerbation. DATA SOURCE: Primary articles and systematic review provided by the
      Cochrane Airways Review Group of the Cochrane Library identified by MEDLINE
      search (1966-February 2004) and through secondary sources. DATA SYNTHESIS: The
      Cochrane review included 21 randomized clinical trials conducted in hospital
      emergency departments comparing clinical outcomes following beta(2) agonist
      administration via a nebulizer or a metered dose inhaler with holding chamber.
      Although the relative risk ratio of hospital admission with metered dose inhaler
      and holding chamber did not differ in children or in adults compared to the
      nebulizer delivery, none of the individual studies reviewed were powered to
      detect a difference in the rate of hospital admission. Specific factors in the
      treatment of acute asthma such as assessment of severity, appropriate outcome
      selection, appropriate dose selection, and appropriate delivery systems need to
      be considered to critically evaluate the literature. CONCLUSION: Although
      available randomized clinical trials suggest equivalency of metered dose inhaler
      plus holding chambers and nebulized delivery of inhaled beta(2) agonists, these
      trials are biased to show no difference in response. There is no data to support
      the advantage of one method over the other in mild to moderate asthmatic patients
      either clinically or economically.

PMID- 23118702
TI  - The ABC's of Acid-Base Balance.
AB  - A step-wise systematic approach can be used to determine the etiology and proper
      management of acid-base disorders. The objectives of this article are to: (1)
      discuss the physiologic processes involved in acid-base disturbances, (2)
      identify primary and secondary acid-base disturbances based upon arterial blood
      gas and laboratory measurements, (3) utilize the anion gap for diagnostic
      purposes, and (4) outline a stepwise approach for interpretation and treatment of
      acid-base disorders. Case studies are used to illustrate the application of the
      discussed systematic approach.

PMID- 23118703
TI  - Clinical management of infants and children with gastroesophageal reflux disease.
AB  - Gastroesophageal reflux refers to the passage of gastric contents including food,
      acid, and digestive enzymes up into the esophagus. Reflux is most commonly
      recognized in infants when it is associated with regurgitation, known as
      "spitting up," and it is usually a self-limited, benign process that has little
      or no effect on normal weight gain or development. Adults and adolescents may
      also have reflux, which is usually either asymptomatic or recognized as dyspepsia
      or "heartburn." Gastroesophageal reflux disease (GERD) is defined as symptoms or
      complications that result from reflux. Most evidence suggests the mechanism of
      reflux is due to transient relaxations of the lower esophageal sphincter at
      inappropriate times. The diagnosis of suspected GERD in infants and children
      depends on the age and the presenting symptoms. A thorough history, physical
      examination, and growth charts are sufficient for the evaluation and diagnosis of
      GERD in most infants with recurrent vomiting or children with regurgitation and
      heartburn. Additional evaluation may include an upper gastrointestinal series,
      esophageal pH monitoring, or endoscopy. The goals of GERD management are
      eliminating symptoms, healing esophagitis, preventing complications, promoting
      normal weight gain and growth, and maintaining remission. Therapeutic options
      include lifestyle changes, pharmacologic therapy, and anti-reflux surgery.
      Currently available pharmacologic agents for the treatment of GERD include
      antacids, mucosal protectants, prokinetic agents, and acid suppressants.

PMID- 23118704
TI  - Chemical stability of extemporaneously prepared Lorazepam suspension at two
      temperatures.
AB  - The objective of this study was to determine the chemical stability of
      extemporaneously prepared lorazepam suspension (1 mg/mL) stored at two
      temperatures (4 degrees C and 22 degrees C) for 3 months. Lorazepam tablets
      marketed by two manufacturers (Mylan Pharmaceuticals and Watson Laboratories)
      were used to extemporaneously formulate two independently prepared suspensions.
      Each suspension was prepared using sterile water, Ora-Plus((r)) and Ora
      Sweet((r)) to achieve a final concentration of 1 mg/mL. The two brands of tablets
      required different volumes of vehicles to prepare a pharmaceutically optimal
      suspension. The suspensions were stored in amber glass bottles at 4 degrees C and
      22 degrees C for 91 days. Samples were analyzed by high performance liquid
      chromatography at baseline and on days 2, 3, 7, 14, 21, 28, 42, 63, and 91. The
      suspensions were considered stable if the mean lorazepam concentration remained
      greater than 90% of the initial concentration.The chemical stabilities of these
      two extemporaneously prepared lorazepam suspensions were comparable throughout
      the study. Both lorazepam suspensions were stable for 63 days when stored at 4
      degrees C or 22 degrees C, and both were stable for 91 days when refrigerated at
      4 degrees C. When stored at room temperature, the suspension prepared from the
      Watson tablet retained 88.9 +/- 1.4% of the initial concentration on day 91 and
      was therefore considered unstable, while the suspension prepared from the Mylan
      tablet was stable for the entire 91-day study.

PMID- 23118705
TI  - The Effects of Increasing Doses of Ranitidine on Gastric pH in Children.
AB  - BACKGROUND: Ranitidine is widely used for gastroesophageal reflux disease (GERD)
      in children, but optimal dosing is unclear. We compared effects of weight-based
      doses of oral ranitidine on gastric pH in children with clinical GERD. METHODS:
      Children ages 4-11 years with clinical GERD were enrolled in a multi-center
      prospective randomized study comparing a fixed dose of ranitidine (Zantac 75)
      with placebo after an overnight fast; gastric pH was measured for 6 h after the
      fixed dose (Phase 1). Of the six enrollees from our center, four received active
      drug during Phase 1; 12 h after the fixed dose, these four children received
      ranitidine 5 mg/kg (maximum 150 mg) and gastric pH was measured for another 6-12
      hours (Phase 2). This report details the effects of two dose ranges (Low Dose, <
      3 mg/kg/dose, and High Dose, >= 3 mg/kg/dose) on gastric pH in children. RESULTS:
      The four children were 6.9-11.3 years old and weighed 20.4-49.5 kg. The Low Doses
      were 1.5-2.7 mg/kg; the High Doses were 3-5 mg/kg. Although the mean percentage
      of time with gastric pH > 4 during the entire 6 hours following dosing was
      similar after Low and High Dose (50% vs. 57%, NS), during the last two hours of
      this interval the mean percentage of time with gastric pH > 4 was only 29% for
      Low Dose vs. 89% for High Dose (P = 0.006). Moreover, during those two hours,
      none of the Low Doses kept gastric pH above 4 for > 60% of the time, while all of
      the High Doses kept pH above 4 for > 60% of the time (P = 0.03). In three of four
      patients who underwent extended (9-12 h) gastric pH monitoring after High Dose
      ranitidine, gastric pH was above 4 for more than 40% of total time. CONCLUSIONS:
      Doses of ranitidine >= 3 mg/kg/dose may be required for acid suppression lasting
      beyond 6 hours.

PMID- 23118706
TI  - Fosphenytoin: current place in therapy.
AB  - Fosphenytoin is a parenteral phosphate ester prodrug of phenytoin developed to
      overcome the limitations associated with parenteral administration of phenytoin.
      Despite potential clinical advantages, pharmacoeconomic concerns have prevented
      widespread substitution of parenteral phenytoin with fosphenytoin. The purposes
      of this descriptive review are to (1) highlight recent clinical and
      pharmacoeconomic data regarding the therapeutic decision to use phenytoin or
      fosphenytoin for the parenteral management of acute seizures, and (2) discuss the
      implications of fosphenytoin use in neonatal and pediatric patients. Supporting
      recent, multidisciplinary, consensus guidelines, it is our opinion that each
      patient should be evaluated individually to identify those who will benefit most
      from fosphenytoin. Such patients may include those without intravenous or enteral
      access, those requiring parenteral therapy with tenuous peripheral intravenous
      access, and pediatric and neonatal patients. Additionally, institution-specific
      cost analyses should be done to assure the most appropriate agent is being used,
      while being sensitive to the potential disparate risk profiles between patient
      populations. Until the issues of safety relative to cost are objectively
      ameliorated, individual clinicians will likely use their own experience to
      dictate the place of fosphenytoin in their respective practices.

PMID- 23118707
TI  - Liver disease and parenteral nutrition in an adolescent with cystic fibrosis.

PMID- 23118708
TI  - Pediatric news.

PMID- 23118709
TI  - Polifeprosan 20, 3.85% carmustine slow-release wafer in malignant glioma:
      evidence for role in era of standard adjuvant temozolomide.
AB  - The Polifeprosan 20 with carmustine (BCNU, bis-chloroethylnitrosourea,
      Gliadel((r))) polymer implant wafer is a biodegradable compound containing 3.85%
      carmustine which slowly degrades to release carmustine and protects it from
      exposure to water with resultant hydrolysis until the time of release. The
      carmustine implant wafer was demonstrated to improve survival in blinded placebo
      controlled trials in selected patients with newly diagnosed or recurrent
      malignant glioma, with little increased risk of adverse events. Based on these
      trials and other supporting data, US and European regulatory authorities granted
      approval for its use in recurrent and newly diagnosed malignant glioma, and it
      remains the only approved local treatment. The preclinical and clinical data
      suggest that it is optimally utilized primarily in the proportion of patients who
      may have total or near total removal of gross tumor. The aim of this work was to
      review the evidence for the use of carmustine implants in the management of
      malignant astrocytoma (World Health Organization grades III and IV), including
      newly diagnosed and recurrent disease, especially in the setting of a standard of
      care that has changed since the randomized trials were completed. Therapy has
      evolved such that patients now generally receive temozolomide chemotherapy during
      and after radiotherapy treatment. For patients undergoing repeat resection for
      malignant glioma, a randomized, blinded, placebo-controlled trial demonstrated a
      median survival for 110 patients who received carmustine polymers of 31 weeks
      compared with 23 weeks for 122 patients who only received placebo polymers. The
      benefit achieved statistical significance only on analysis adjusting for
      prognostic factors rather than for the randomized groups as a whole (hazard ratio
      = 0.67, P = 0.006). A blinded, placebo-controlled trial has also been performed
      for carmustine implant placement in newly diagnosed patients prior to standard
      radiotherapy. Median survival was improved from 11.6 to 13.9 months (P = 0.03),
      with a 29% reduction in the risk of death. When patients with glioblastoma
      multiforme alone were analyzed, the median survival improved from 11.4 to 13.5
      months, but this improvement was not statistically significant. When a Cox's
      proportional hazard model was utilized to account for other potential prognostic
      factors, there was a significant 31% reduction in the risk of death (P = 0.04) in
      this subgroup. Data from other small reports support these results and confirm
      that the incidence of adverse events does not appear to be increased
      meaningfully. Given the poor prognosis without possibility of cure, these
      benefits from a treatment with a favorable safety profile were considered
      meaningful. There is randomized evidence to support the use of carmustine wafers
      placed during resection of recurrent disease. Therefore, although there is
      limited specific evidence, this treatment is likely to be efficacious in an
      environment when nearly all patients receive temozolomide as part of initial
      management. Given that half of the patients in the randomized trial assessing the
      value of carmustine implants in recurrent disease had received prior
      chemotherapy, it is likely that this remains a valuable treatment at the time of
      repeat resection, even after temozolomide. There are data from multiple reports
      to support safety. Although there is randomized evidence to support the use of
      this therapy in newly diagnosed patients who will receive radiotherapy alone, it
      is now standard to administer both adjuvant temozolomide and radiotherapy. There
      are survival outcome reports for small cohorts of patients receiving temozolomide
      with radiotherapy, but this information is not sufficient to support firm
      recommendations. Based on the rationale and evidence of safety, this approach
      appears to be a reasonable option as more information is acquired. Available data
      support the safety of using carmustine wafers in this circumstance, although
      special attention to surgical guidelines for implanting the wafers is warranted.

PMID- 23118710
TI  - Repeatability and relative validity of a quantitative food-frequency
      questionnaire among French adults.
AB  - BACKGROUND: A 50-item self-administered food frequency questionnaire (FFQ) was
      developed for French adults, to assess the intake of energy, 10 macronutrients,
      11 vitamins, and 11 minerals, and to be used in the context of a medical
      consultation. OBJECTIVE: To assess the repeatability and relative validity of
      this FFQ compared to a 7-day diet record (7-DR). DESIGN: A total of 54 and 100
      French adults were included in the repeatability and validation studies,
      respectively. Repeatability was assessed using two FFQs, the second carried out 3
      weeks after the first. In the validation study, subjects first completed the FFQ,
      then the 7-DR the following week. Energy and nutrient intakes were compared using
      Pearson correlation. The degree of misclassification by the FFQ, compared to the
      7-DR, was calculated by a contingency table of quintiles. Bland-Altman plots
      assessed the correlation between FFQ and 7-DR across the intake range. RESULTS:
      Repeatability for intake, explored by Pearson correlation, was 0.62-0.90 (median:
      0.81). Relative validity, as determined by Pearson correlation for the nutrient
      intake derived from the FFQ and 7-DR, was 0.36-0.80 (0.64). The FFQ tended to
      report higher fiber and micronutrient intake than 7-DR. Misclassification into
      opposite quintiles ranged 0-6% (1%), whereas classification into same or adjacent
      quintiles ranged 59-83% (74%). Bland-Altman plots showed good agreement for most
      nutrients across the range of intake. CONCLUSION: This new FFQ showed a high
      repeatability and good relative validity, and thanks to its short length, should
      be a useful tool for rapidly evaluating the nutrient intake of French adults.

PMID- 23118712
TI  - Polyunsaturated Fatty acids of marine macroalgae: potential for nutritional and
      pharmaceutical applications.
AB  - As mammals are unable to synthesize essential polyunsaturated fatty acids (PUFA),
      these compounds need to be taken in through diet. Nowadays, obtaining essential
      PUFA in diet is becoming increasingly difficult; therefore this work investigated
      the suitability of using macroalgae as novel dietary sources of PUFA. Hence, 17
      macroalgal species from three different phyla (Chlorophyta, Phaeophyta and
      Rhodophyta) were analyzed and their fatty acid methyl esters (FAME) profile was
      assessed. Each phylum presented a characteristic fatty acid signature as
      evidenced by clustering of PUFA profiles of algae belonging to the same phylum in
      a Principal Components Analysis. The major PUFA detected in all phyla were C(18)
      and C(20), namely linoleic, arachidonic and eicosapentaenoic acids. The obtained
      data showed that rhodophytes and phaeophytes have higher concentrations of PUFA,
      particularly from the n-3 series, thereby being a better source of these
      compounds. Moreover, rhodophytes and phaeophytes presented "healthier" ?n-6/?n-3
      and PUFA/saturated fatty acid ratios than chlorophytes. Ulva was an exception
      within the Chlorophyta, as it presented high concentrations of n-3 PUFA, alpha
      linolenic acid in particular. In conclusion, macroalgae can be considered as a
      potential source for large-scale production of essential PUFA with wide
      applications in the nutraceutical and pharmacological industries.

PMID- 23118711
TI  - Sinularin from indigenous soft coral attenuates nociceptive responses and spinal
      neuroinflammation in carrageenan-induced inflammatory rat model.
AB  - Three decades ago, the marine-derived compound sinularin was shown to have anti
      edematous effects on paw edema induced by carrageenan or adjuvant. To the best of
      our knowledge, no new studies were conducted to explore the bioactivity of
      sinularin until we reported the analgesic properties of sinularin based on in
      vivo experiments. In the present study, we found that sinularin significantly
      inhibits the upregulation of proinflammatory proteins, inducible nitric oxide
      synthase (iNOS), and cyclooxygenase-2 (COX-2) and upregulates the production of
      transforming growth factor-beta (TGF-beta) in lipopolysaccharide (LPS)-stimulated
      murine macrophage RAW 264.7 cells according to western blot analysis. We found
      that subcutaneous (s.c.) administration of sinularin (80 mg/kg) 1 h before
      carrageenan injection significantly inhibited carrageenan-induced nociceptive
      behaviors, including thermal hyperalgesia, mechanical allodynia, cold allodynia,
      and hindpaw weight-bearing deficits. Further, s.c. sinularin (80 mg/kg)
      significantly inhibited carrageenan-induced microglial and astrocyte activation
      as well as upregulation of iNOS in the dorsal horn of the lumbar spinal cord.
      Moreover, s.c. sinularin (80 mg/kg) inhibited carrageenan-induced tissue
      inflammatory responses, redness and edema of the paw, and leukocyte infiltration.
      The results of immunohistochemical studies indicate that s.c. sinularin (80
      mg/kg) could upregulate production of TGF-beta1 in carrageenan-induced inflamed
      paw tissue. The present results demonstrate that systemic sinularin exerts
      analgesic effects at the behavioral and spinal levels, which are associated with
      both inhibition of leukocyte infiltration and upregulation of TGF-beta1.

PMID- 23118713
TI  - Characterization of isoforms of the lectin isolated from the red algae
      Bryothamnion seaforthii and its pro-healing effect.
AB  - Lectins are a structurally heterogeneous group of proteins that have specific
      binding sites for carbohydrates and glycoconjugates. Because of their
      biotechnological potential, lectins are widely used in biomedical research. The
      present study aimed to evaluate the healing potential of the lectin isolated from
      the marine red alga Bryothamnion seaforthii (BSL). The lectin was purified using
      ion exchange chromatography with DEAE cellulose and characterized using tandem
      mass spectrometry. For healing tests, skin wounds were induced in the dorsal
      thoracic region of mice. These animals were randomly divided into three groups
      and subjected to topical treatment for 12 days with BSL, bovine serum albumin and
      150 mM NaCl. To evaluate the potential of each treatment, the animals were
      anesthetized and sacrificed on days 2, 7 and 12, respectively. The parameters
      evaluated included the wound area, the proportion of wound closure and the
      histological diagnosis. The wound closure was more effective with BSL
      (Postoperative Day 7 and 12) than controls. The luminal epithelium was completely
      restructured; the presence of collagen in the dermis and the strongly active
      presence of young skin annexes demonstrate the potential of treatment with BSL
      compared with controls. Our findings suggest that BSL has pro-healing properties
      and can be a potential medical process in the treatment of acute wounds.

PMID- 23118714
TI  - Efficient heterologous transformation of Chlamydomonas reinhardtii npq2 mutant
      with the zeaxanthin epoxidase gene isolated and characterized from Chlorella
      zofingiensis.
AB  - In the violaxanthin cycle, the violaxanthin de-epoxidase and zeaxanthin epoxidase
      catalyze the inter-conversion between violaxanthin and zeaxanthin in both plants
      and green algae. The zeaxanthin epoxidase gene from the green microalga Chlorella
      zofingiensis (Czzep) has been isolated. This gene encodes a polypeptide of 596
      amino acids. A single copy of Czzep has been found in the C. zofingiensis genome
      by Southern blot analysis. qPCR analysis has shown that transcript levels of
      Czzep were increased after zeaxanthin formation under high light conditions. The
      functionality of Czzep gene by heterologous genetic complementation in the
      Chlamydomonas mutant npq2, which lacks zeaxanthin epoxidase (ZEP) activity and
      accumulates zeaxanthin in all conditions, was analyzed. The Czzep gene was
      adequately inserted in the pSI105 vector and expressed in npq2. The positive
      transformants were able to efficiently convert zeaxanthin into violaxanthin, as
      well as to restore their maximum quantum efficiency of the PSII (Fv/Fm). These
      results show that Chlamydomonas can be an efficient tool for heterologous
      expression and metabolic engineering for biotechnological applications.

PMID- 23118716
TI  - Meroterpenes from endophytic fungus A1 of mangrove plant Scyphiphora
      hydrophyllacea.
AB  - Four new meroterpenes, guignardones F-I (1-4), together with two known compounds
      guignardones A (5) and B (6) were isolated from the endophytic fungus A1 of the
      mangrove plant Scyphiphora hydrophyllacea. Their structures and relative
      configurations were elucidated by spectroscopic data and single-crystal X-ray
      crystallography. A possible biogenetic pathway of compounds 1-6 was also
      proposed. All compounds were evaluated for inhibitory activity against
      methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus aureus.

PMID- 23118715
TI  - Antinociceptive and anti-inflammatory activities of crude methanolic extract of
      red alga Bryothamnion triquetrum.
AB  - The marine environment is an extraordinary reservoir of bioactive natural
      products, many of which exhibit chemical and structural features not found in
      terrestrial natural products. In this regard, the aim of this study was to
      investigate the possible antinociceptive and anti-inflammatory activities of a
      crude methanolic extract of the red alga Bryothamnion triquetrum (BT-MeOH) in
      murine models. Groups of Swiss mice of both sexes (25-30 g) were used throughout
      the experiments. The potential antinociceptive of BT-MeOH was evaluated by means
      of the following tests: acetic acid-induced writhing, hot-plate test and
      glutamate- and formalin-induced nociception. The anti-inflammatory activity of BT
      MeOH was investigated using the zymosan A-induced peritonitis test. The tests
      were conducted using 100 mg/kg (p.o.) BT-MeOH, 33.3 mg/kg (p.o.) dipyrone, 35.7
      mg/kg (p.o.) indomethacin and 5.7 mg/kg (s.c.) morphine. The extract and all
      standard drugs were administered 40 min before the nociceptive/inflammatory
      stimulus. In the acetic acid-induced writhing test, BT-MeOH and dipyrone
      inhibited the nociceptive response by 55.9% (22.2 +/- 2.0 writhings; p < 0.01)
      and 80.9% (9.6 +/- 2.1 writhings; p < 0.01). In the hot-plate test, BT-MeOH did
      not increase the latency time of the animals in the time evaluated. In addition,
      BT-MeOH inhibited glutamate-induced nociception by 50.1%. While BT-MeOH did not
      inhibit the neurogenic phase in formalin-induced nociception, the inflammatory
      phase was inhibited by 53.1% (66.8 +/- 14.2 s; p < 0.01). Indomethacin inhibited
      the inflammatory phase by 60.2% (56.8 +/- 8.7 s; p < 0.01). In the zymosan
      induced peritonitis test, BT-MeOH inhibited 55.6% (6.6 +/- 0.2 * 10(6)
      leukocytes/mL; p < 0.01) of leukocyte migration, while indomethacin inhibited
      78.1% (3.2 +/- 0.1 * 10(6) leukocytes/mL; p < 0.01). Based on the results
      obtained in this study, we conclude that BT-MeOH has peripheral antinociceptive
      and anti-inflammatory activities. However, more studies need to be conducted to
      confirm these properties.

PMID- 23118717
TI  - Antiproliferative activity of fucan nanogel.
AB  - Sulfated fucans comprise families of polydisperse natural polysaccharides based
      on sulfated L-fucose. Our aim was to investigate whether fucan nanogel induces
      cell-specific responses. To that end, a non toxic fucan extracted from
      Spatoglossum schroederi was chemically modified by grafting hexadecylamine to the
      polymer hydrophilic backbone. The resulting modified material (SNFuc) formed
      nanosized particles. The degree of substitution with hydrophobic chains was close
      to 100%, as estimated by elemental analysis. SNFfuc in aqueous media had a mean
      diameter of 123 nm and zeta potential of -38.3 +/- 0.74 mV, as measured by
      dynamic light scattering. Nanoparticles conserved their size for up to 70 days.
      SNFuc cytotoxicity was determined using the MTT assay after culturing different
      cell lines for 24 h. Tumor-cell (HepG2, 786, H-S5) proliferation was inhibited by
      2.0%-43.7% at nanogel concentrations of 0.05-0.5 mg/mL and rabbit aorta
      endothelial cells (RAEC) non-tumor cell line proliferation displayed inhibition
      of 8.0%-22.0%. On the other hand, nanogel improved Chinese hamster ovary (CHO)
      and monocyte macrophage cell (RAW) non-tumor cell line proliferation in the same
      concentration range. The antiproliferative effect against tumor cells was also
      confirmed using the BrdU test. Flow cytometric analysis revealed that the fucan
      nanogel inhibited 786 cell proliferation through caspase and caspase-independent
      mechanisms. In addition, SNFuc blocks 786 cell passages in the S and G2-M phases
      of the cell cycle.

PMID- 23118718
TI  - New cembrane diterpenoids from a Hainan soft coral Sinularia sp.
AB  - Five new cembrane diterpenoids, named sinuflexibilins A-E (1-5), along with nine
      other known diterpenoids (6-14), have been isolated from the organic extract of a
      Hainan soft coral Sinularia sp. Their structures were determined on the basis of
      extensive spectroscopic analyses and by comparison of their spectral data with
      those of related metabolites. Compound 13, flexibilide, exhibited significant
      inhibitory activity of NF-kappaB activation using the cell-based HEK293 NF-kappaB
      luciferase reporter gene assay.

PMID- 23118719
TI  - The antiangiogenic compound aeroplysinin-1 induces apoptosis in endothelial cells
      by activating the mitochondrial pathway.
AB  - Aeroplysinin-1 is a brominated metabolite extracted from the marine sponge
      Aplysina aerophoba that has been previously characterized by our group as a
      potent antiangiogenic compound in vitro and in vivo. In this work, we provide
      evidence of a selective induction of apoptosis by aeroplysinin-1 in endothelial
      cells. Studies on the nuclear morphology of treated cells revealed that
      aeroplysinin-1 induces chromatin condensation and nuclear fragmentation, and it
      increases the percentage of cells with sub-diploid DNA content in endothelial,
      but not in HCT-116, human colon carcinoma and HT-1080 human fibrosarcoma cells.
      Treatment of endothelial cells with aeroplysinin-1 induces activation of caspases
      2, -3, -8 and -9, as well as the cleavage of apoptotic substrates, such as poly
      (ADP-ribose) polymerase and lamin-A in a caspase-dependent mechanism. Our data
      indicate a relevant role of the mitochondria in the apoptogenic activity of this
      compound. The observation that aeroplysinin-1 prevents the phosphorylation of Bad
      relates to the mitochondria-mediated induction of apoptosis by this compound.

PMID- 23118720
TI  - Clinical trial: marine lipid suppositories as laxatives.
AB  - Cod-liver oil and other marine products containing polyunsaturated fatty acids
      have anti-inflammatory, anti-bacterial and anti-viral effects and may be useful
      in the treatment of various inflammatory and infectious diseases. We developed
      suppositories and ointment with 30% free fatty acid (FFA) extract from omega-3
      fish oil. Our purpose was to evaluate the safety of marine lipid suppositories
      and ointment in healthy volunteers and to explore the laxative effect of the
      suppositories. Thirty healthy volunteers were randomized either to a study group
      administrating 30% FFA suppositories and applying 30% FFA ointment to the
      perianal region twice per day for two weeks, or to a control group using placebo
      suppositories and ointment in a double blinded manner. RESULTS: No serious toxic
      effects or irritation were observed. In the study group 93% felt the urge to
      defecate after administration of the suppositories as compared to 37% in the
      control group (P = 0.001). Subsequently 90% in the study group defecated,
      compared to 33% in the control group (P = 0.001). CONCLUSION: The marine lipid
      suppositories and ointment were well tolerated with no significant toxic side
      effects observed during the study period. The suppositories have a distinct
      laxative effect and we aim to explore this effect in further clinical trials.

PMID- 23118721
TI  - In vivo induction of apoptosis by fucoxanthin, a marine carotenoid, associated
      with down-regulating STAT3/EGFR signaling in sarcoma 180 (S180) xenografts
      bearing mice.
AB  - Previous in vitro researches have showed that fucoxanthin, a natural carotenoid
      isolated from sargassum, can inhibit proliferation or induce apoptosis in human
      neuroblastoma, hepatoma, leukemia, colon carcinoma, prostate cancer or urinary
      bladder cancer cells. But the precise mechanism by which fucoxanthin exerts
      anticarcinogenic effects is not yet fully understood. In this study, we performed
      an in vivo study to investigate the anti-tumor effect and mechanisms of
      fucoxanthin on xenografted sarcoma 180 (S180) in mice. Results revealed that
      fucoxanthin significantly inhibited the growth of sarcoma at the dose of 50 or
      100 mg/kg. TUNEL analysis showed that the number of positive cells in the
      fucoxanthin-treated group was higher than that in the control group. Western
      blotting analysis also revealed the suppressed expression of bcl-2 and enhanced
      expression of cleaved caspase-3 by fucoxanthin. In addition, immunohistochemistry
      analysis and Western blotting analysis showed that fucoxanthin significantly
      decreased the expressions of survivin and vascular endothelial growth factor
      (VEGF). Most importantly, fucoxanthin inhibited the expressions of the epidermal
      growth factor receptor (EGFR) and STAT3 and phosphorylated STAT3 proteins. These
      results indicated that in vivo induction of apoptosis by fucoxanthin is
      associated with down-regulating STAT3/EGFR signaling in S180 xenografts-bearing
      mice.

PMID- 23118723
TI  - Application of HPLC-NMR in the identification of plocamenone and isoplocamenone
      from the marine red alga Plocamium angustum.
AB  - A combination of on-line HPLC-NMR and off-line chemical investigations has
      resulted in the identification of the previously reported polyhalogenated
      monoterpene plocamenone, together with the new structural analogue isoplocamenone
      from the crude extract of the marine alga Plocamium angustum. On-flow and stop
      flow HPLC-NMR analyses (including the acquisition of WET 2D NMR spectra) rapidly
      assisted in the identification of the major component plocamenone and in the
      partial identification of its unstable double bond isomer isoplocamenone.
      Conventional off-line isolation and structural characterization techniques were
      employed to unequivocally confirm both structures, leading to a structural
      revision for plocamenone, as well as to obtain sufficient quantities for
      biological testing.

PMID- 23118722
TI  - Isolation and characterization of a lycopene epsilon-cyclase gene of Chlorella
      (Chromochloris) zofingiensis. Regulation of the carotenogenic pathway by nitrogen
      and light.
AB  - The isolation and characterization of the lycopene epsilon-cyclase gene from the
      green microalga Chlorella (Chromochloris) zofingiensis (Czlcy-e) was performed.
      This gene is involved in the formation of the carotenoids alpha-carotene and
      lutein. Czlcy-e gene encoded a polypeptide of 654 amino acids. A single copy of
      Czlcy-e was found in C. zofingiensis. Functional analysis by heterologous
      complementation in Escherichia coli showed the ability of this protein to convert
      lycopene to delta-carotene. In addition, the regulation of the carotenogenic
      pathway by light and nitrogen was also studied in C. zofingiensis. High
      irradiance stress did not increase mRNA levels of neither lycopene beta-cyclase
      gene (lcy-b) nor lycopene epsilon-cyclase gene (lcy-e) as compared with low
      irradiance conditions, whereas the transcript levels of psy, pds, chyB and bkt
      genes were enhanced, nevertheless triggering the synthesis of the secondary
      carotenoids astaxanthin, canthaxanthin and zeaxanthin and decreasing the levels
      of the primary carotenoids alpha-carotene, lutein, violaxanthin and beta
      carotene. Nitrogen starvation per se enhanced mRNA levels of all genes
      considered, except lcy-e and pds, but did not trigger the synthesis of
      astaxanthin, canthaxanthin nor zeaxanthin. The combined effect of both high light
      and nitrogen starvation stresses enhanced significantly the accumulation of these
      carotenoids as well as the transcript levels of bkt gene, as compared with the
      effect of only high irradiance stress.

PMID- 23118724
TI  - Briacavatolides D-F, new briaranes from the Taiwanese octocoral Briareum
      excavatum.
AB  - In the continued search for novel bioactive substances from the Taiwanese
      octocoral Briareum excavatum collected at Orchid Island, three new briarane-type
      diterpenoids, briacavatolides D-F (1-3) were isolated from the acetone extract.
      The structures of these compounds were elucidated by extensive NMR spectroscopic
      analysis and physical data. The anti-HCMV (human cytomegalovirus) activity of 1-3
      and their cytotoxicity against selected cancer cell lines were evaluated.

PMID- 23118725
TI  - Dose-response on the chemopreventive effects of sarcophine-diol on UVB-induced
      skin tumor development in SKH-1 hairless mice.
AB  - Sarcophine-diol (SD) is a lactone ring-opened analogue of sarcophine. It has
      shown chemopreventive effects on chemically-induced skin tumor development in
      female CD-1 mice, as well as in a UVB-induced skin tumor development model in
      hairless SKH-1 mice at a dose of 30 MUg SD applied topically and 180 mJ/cm(2)
      UVB. The objective of this study was to determine the dose-response on the
      chemopreventive effects of SD on SKH-1 hairless mice when exposed to a UVB
      radiation dose of 30 mJ/cm(2). This UVB dose better represents chronic human skin
      exposure to sunlight leading to skin cancer than previous studies applying much
      higher UVB doses. Carcinogenesis was initiated and promoted by UVB radiation.
      Female hairless SKH-1 mice were divided into five groups. The control group was
      topically treated with 200 MUL of acetone (vehicle), and the SD treatment groups
      were topically treated with SD (30 MUg, 45 MUg, and 60 MUg dissolved in 200 MUL
      of acetone) 1 h before UVB radiation (30 mJ/cm(2)). The last group of animals
      received 60 MUg SD/200 MUL acetone without UVB exposure. These treatments were
      continued for 27 weeks. Tumor multiplicity and tumor volumes were recorded on a
      weekly basis for 27 weeks. Weight gain and any signs of toxicity were also
      closely monitored. Histological characteristics and the proliferating cell
      nuclear antigen (PCNA) were evaluated in the mice skin collected at the end of
      the experiment. The dose-response study proved a modest increase in
      chemopreventive effects with the increase in SD dose. SD reduced the number of
      cells positively stained with PCNA proliferation marker in mice skin. The study
      also showed that SD application without UVB exposure has no effect on the
      structure of skin. The results from this study suggest that broader range doses
      of SD are necessary to improve the chemopreventive effects.

PMID- 23118726
TI  - Cyclic Bis-1,3-dialkylpyridiniums from the sponge Haliclona sp.
AB  - Eight novel cyclic bis-1,3-dialkylpyridiniums, as well as two known compounds
      from the cyclostellettamine class, were isolated from the sponge Haliclona sp.
      from Korea. Structures of these novel compounds were determined using combined
      NMR and FAB-MS/MS analyses. Several of these compounds exhibited moderate
      cytotoxic and antibacterial activities against A549 cell-line and Gram-positive
      strains, respectively. The structure-activity relationships of
      cyclostellettamines are discussed based on their bioactivities.

PMID- 23118728
TI  - Cell therapy for stroke: use of local astrocytes.
AB  - Stroke refers to a variety of conditions caused by the occlusion or hemorrhage of
      blood vessels supplying the brain, which is one of the main causes of death and
      the leading cause of disability worldwide. In the last years, cell-based
      therapies have been proposed as a new approach to ameliorate post-stroke
      deficits. However, the most appropriate type of cell to be used in such
      therapies, as well as their sources, remains a matter of intense research. A good
      candidate cell should, in principle, display high plasticity to generate diverse
      types of neurons and, at the same type, low risk to cause undesired outcomes,
      such as malignant transformation. Recently, a new approach grounded on the
      reprogramming of endogenous astrocytes toward neuronal fates emerged as an
      alternative to restore neurological functions in several central nervous system
      diseases. In this perspective, we review data about the potential of astrocytes
      to become functional neurons following expression of neurogenic genes and discuss
      the potential benefits and risks of reprogramming astrocytes in the glial scar to
      replace neurons lost after stroke.

PMID- 23118727
TI  - Glycine receptor mutants of the mouse: what are possible routes of inhibitory
      compensation?
AB  - Defects in glycinergic inhibition result in a complex neuromotor disorder in
      humans known as hyperekplexia (OMIM 149400) with similar phenotypes in rodents
      characterized by an exaggerated startle reflex and hypertonia. Analogous to
      genetic defects in humans single point mutations, microdeletions, or insertions
      in the Glra1 gene but also in the Glrb gene underlie the pathology in mice. The
      mutations either localized in the alpha (spasmodic, oscillator, cincinnati,
      Nmf11) or the beta (spastic) subunit of the glycine receptor (GlyR) are much less
      tolerated in mice than in humans, leaving the question for the existence of
      different regulatory elements of the pathomechanisms in humans and rodents. In
      addition to the spontaneous mutations, new insights into understanding of the
      regulatory pathways in hyperekplexia or glycine encephalopathy arose from the
      constantly increasing number of knock-out as well as knock-in mutants of GlyRs.
      Over the last five years, various efforts using in vivo whole cell recordings
      provided a detailed analysis of the kinetic parameters underlying glycinergic
      dysfunction. Presynaptic compensation as well as postsynaptic compensatory
      mechanisms in these mice by other GlyR subunits or GABA(A) receptors, and the
      role of extra-synaptic GlyRs is still a matter of debate. A recent study on the
      mouse mutant oscillator displayed a novel aspect for compensation of
      functionality by complementation of receptor domains that fold independently.
      This review focuses on defects in glycinergic neurotransmission in mice discussed
      with the background of human hyperekplexia en route to strategies of
      compensation.

PMID- 23118729
TI  - Is spike frequency adaptation an artefact? Insight from human studies.

PMID- 23118730
TI  - The spatiotemporal dynamics of longevity-defining cellular processes and its
      modulation by genetic, dietary, and pharmacological anti-aging interventions.

PMID- 23118731
TI  - The Build-up of Auditory Stream Segregation: A Different Perspective.
AB  - The build-up of auditory stream segregation refers to the notion that sequences
      of alternating A and B sounds initially tend to be heard as a single stream, but
      with time appear to split into separate streams. The central assumption in the
      analysis of this phenomenon is that streaming sequences are perceived as one
      stream at the beginning by default. In the present study, we test the validity of
      this assumption and document its impact on the apparent build-up phenomenon.
      Human listeners were presented with ABAB sequences, where A and B were harmonic
      tone complexes of seven different fundamental frequency separations (Deltaf)
      ranging from 2 to 14 semitones. Subjects had to indicate, as promptly as
      possible, their initial percept of the sequences, as either "one stream" or "two
      streams," and any changes thereof during the sequences. We found that subjects
      did not generally indicate a one-stream percept at the beginning of streaming
      sequences. Instead, the first perceptual decision depended on Deltaf, with the
      probability of a one-stream percept decreasing, and that of a two-stream percept
      increasing, with increasing Deltaf. Furthermore, subjects required some time to
      make and report a decision on their perceptual organization. Taking this time
      into account, the resulting time courses of two-stream probabilities differ
      markedly from those suggested by the conventional analysis. A build-up-like
      increase in two-stream probability was found only for the Deltaf of six
      semitones. At the other Deltaf conditions no or only minor increases in two
      stream probability occurred. These results shed new light on the build-up of
      stream segregation and its possible neural correlates.

PMID- 23118732
TI  - Minds without language represent number through space: origins of the mental
      number line.

PMID- 23118734
TI  - Penetrating insights?

PMID- 23118733
TI  - Controlled cortical impact and craniotomy induce strikingly similar profiles of
      inflammatory gene expression, but with distinct kinetics.
AB  - An immediate consequence of traumatic brain injury (TBI) is the induction of an
      inflammatory response. Mounting data suggest that inflammation is a major
      contributor to TBI-induced brain damage. However, much remains unknown regarding
      the induction and regulation of the inflammatory response to TBI. In this study
      we compared the TBI-induced inflammatory response to severe parenchymal injury
      (controlled cortical impact) vs. mild brain injury (craniotomy) over a 21-day
      period. Our data show that both severe and mild brain injury induce a
      qualitatively similar inflammatory response, involving highly overlapping sets of
      effector molecules. However, kinetic analysis revealed that the inflammatory
      response to mild brain injury is of much shorter duration than the response to
      severe TBI. Specifically, the inflammatory response to severe brain injury
      persists for at least 21 days, whereas the response to mild brain injury returns
      to near baseline values within 10 days post-injury. Our data therefore imply that
      the development of accurate diagnostic tests of TBI severity that are based on
      imaging or biomarker analysis of the inflammatory response may require repeated
      measures over at least a 10-day period, post-injury.

PMID- 23118735
TI  - The microbial ferrous wheel: iron cycling in terrestrial, freshwater, and marine
      environments.

PMID- 23118736
TI  - Sulfonamides identified as plant immune-priming compounds in high-throughput
      chemical screening increase disease resistance in Arabidopsis thaliana.
AB  - Plant activators are agrochemicals that protect crops from diseases by activating
      the plant immune system. To isolate lead compounds for use as practical plant
      activators, we screened two different chemical libraries composed of various
      bioactive substances by using an established screening procedure that can
      selectively identify immune-priming compounds. We identified and characterized a
      group of sulfonamide compounds - sulfameter, sulfamethoxypyridazine,
      sulfabenzamide, and sulfachloropyridazine - among the various isolated candidate
      molecules. These sulfonamide compounds enhanced the avirulent Pseudomonas-induced
      cell death of Arabidopsis suspension cell cultures and increased disease
      resistance in Arabidopsis plants against both avirulent and virulent strains of
      the bacterium. These compounds did not prevent the growth of pathogenic bacteria
      in minimal liquid media at 200 MUM. They also did not induce the expression of
      defense-related genes in Arabidopsis seedlings, at least not at 24 and 48 h after
      treatment, suggesting that they do not act as salicylic acid analogs. In
      addition, although sulfonamides are known to be folate biosynthesis inhibitors,
      the application of folate did not restore the potentiation effects of the
      sulfonamides on pathogen-induced cell death. Our data suggest that sulfonamides
      potentiate Arabidopsis disease resistance by their novel chemical properties.

PMID- 23118737
TI  - Epigenetic drugs: a novel anti-aging strategy?

PMID- 23118738
TI  - Current bioinformatic approaches to identify DNase I hypersensitive sites and
      genomic footprints from DNase-seq data.

PMID- 23118740
TI  - Tracking regional tissue volume and function change in lung using image
      registration.
AB  - We have previously demonstrated the 24-hour redistribution and reabsorption of
      bronchoalveolar lavage (BAL) fluid delivered to the lung during a bronchoscopic
      procedure in normal volunteers. In this work we utilize image-matching procedures
      to correlate fluid redistribution and reabsorption to changes in regional lung
      function. Lung CT datasets from six human subjects were used in this study. Each
      subject was scanned at four time points before and after BAL procedure. Image
      registration was performed to align images at different time points and different
      inflation levels. The resulting dense displacement fields were utilized to track
      tissue volume changes and reveal deformation patterns of local parenchymal tissue
      quantitatively. The registration accuracy was assessed by measuring landmark
      matching errors, which were on the order of 1 mm. The results show that
      quantitative-assessed fluid volume agreed well with bronchoscopist-reported
      unretrieved BAL volume in the whole lungs (squared linear correlation coefficient
      was 0.81). The average difference of lung tissue volume at baseline and after 24
      hours was around 2%, which indicates that BAL fluid in the lungs was almost
      absorbed after 24 hours. Regional lung-function changes correlated with the
      presence of BAL fluid, and regional function returned to baseline as the fluid
      was reabsorbed.

PMID- 23118739
TI  - Non-coding RNA and pseudogenes in neurodegenerative diseases: "The (un)Usual
      Suspects".
AB  - Neurodegenerative disorders and cancer are severe diseases threatening human
      health. The glaring differences between neurons and cancer cells mask the
      processes involved in their pathogenesis. Defects in cell cycle, DNA repair, and
      cell differentiation can determine unlimited proliferation in cancer, or
      conversely, compromise neuronal plasticity, leading to cell death and
      neurodegeneration. Alteration in regulatory networks affecting gene expression
      contribute to human diseases onset, including neurodegenerative disorders, and
      deregulation of non-coding RNAs - particularly microRNAs (miRNAs) - is supposed
      to have a significant impact. Recently, competitive endogenous RNAs (ceRNAs) -
      acting as sponges - have been identified in cancer, indicating a new and
      intricate regulatory network. Given that neurodegenerative disorders and cancer
      share altered genes and pathways, and considering the emerging role of miRNAs in
      neurogenesis, we hypothesize ceRNAs may be implicated in neurodegenerative
      diseases. Here we propose, and computationally predict, such regulatory mechanism
      may be shared between the diseases. It is predictable that similar regulation
      occurs in other complex diseases, and further investigation is needed.

PMID- 23118741
TI  - Effect of ezetimibe on insulin secretion in db/db diabetic mice.
AB  - OBJECTIVE: To investigate the effect of ezetimibe on the insulin secretion in
      db/db mice. METHODS: The db/db diabetic mice aged 8 weeks were randomly assigned
      into 2 groups and intragastrically treated with ezetimibe or placebo for 6 weeks.
      The age matched db/m mice served as controls. At the end of experiment, glucose
      tolerance test was performed and then the pancreas was collected for
      immunohistochemistry. In addition, in vitro perfusion of pancreatic islets was
      employed for the detection of insulin secretion in the first phase. RESULTS: In
      the ezetimibe group, the fasting blood glucose was markedly reduced, and the
      total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were
      significantly lowered when compared with those in the control group (P < 0.05).
      At 120 min after glucose tolerance test, the area under curve in the ezetimibe
      group was significantly smaller than that in the control group (P < 0.05), but
      the AUC(INS0-30) was markedly higher. In vitro perfusion of pancreatic islets
      revealed the first phase insulin secretion was improved. In addition, the insulin
      expression in the pancreas in the ezetimibe group was significantly increased as
      compared to the control group. CONCLUSION: Ezetimibe can improve glucose
      tolerance, recover the first phase insulin secretion, and protect the function of
      beta cells in mice.

PMID- 23118742
TI  - Metformin stimulates FGF21 expression in primary hepatocytes.
AB  - Fibroblast growth factor 21 (FGF21) is a novel metabolic regulator of glucose and
      lipid metabolism; however, the exact mechanism of action and regulation of FGF21
      is not fully understood. Metabolic status plays an important role in the
      regulation of FGF21, and we therefore examined whether metformin, an indirect
      AMPK-activator, regulates FGF21 expression in hepatocytes. FGF21 mRNA and protein
      expression were determined after incubation of primary cultured rat and human
      hepatocytes with metformin for 24 hours. To study the role of AMPK in the
      putative regulation of FGF21, hepatocytes were incubated with Compound C (an AMPK
      inhibitor) in the presence of metformin. A strong dose-dependent increase in
      FGF21 expression was observed in both rat and human hepatocytes treated with
      metformin. This effect was blocked by addition of the AMPK-inhibitor Compound C.
      The study shows that metformin is a potent inducer of hepatic FGF21 expression
      and that the effect of metformin seems to be mediated through AMPK activation. As
      FGF21 therapy normalizes blood glucose in animal models of type 2 diabetes, the
      induction of hepatic FGF21 by metformin might play an important role in
      metformin's antidiabetic effect.

PMID- 23118743
TI  - Genetic dissection of complex genetic factor involved in NIDDM of OLETF rat.
AB  - The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model for obese
      type, noninsulin-dependent diabetes mellitus (NIDDM) in humans. NIDDM in this rat
      model was shown to be regulated by multiple genes. We have identified 14
      quantitative trait loci (QTLs) responsible for NIDDM (Nidd1-14/of) on chromosomes
      1, 5, 7, 8, 9, 11, 12, 14, 16, and 17 by a whole genome search in 160 F2
      progenies obtained by mating the OLETF and the F344 rats. Among these loci, two
      QTLs, Nidd1 and 2/of, were declared significant loci at a genome-wide level.
      Nidd3, 8, 9, and 13/of exhibited heterosis: heterozygotes showing significantly
      higher glucose levels than OLETF or F344 homozygotes. We also found evidence for
      interaction (epistasis) between Nidd1/of and Nidd2/of, between Nidd1/of and
      Nidd10/of, between Nidd2/of and Nidd8/of, and between Nidd2/of and Nidd14/of.
      Furthermore, Nidd6 and 11/of showed linkage with body weight, and Nidd1, 2, 8, 9,
      10, and 12/of had an interaction with body weight. These indicated that NIDDM in
      the OLETF would have a higher degree of genetic complexity. We suggest several
      interesting candidate genes located in rat genomic regions for Nidd1-14/of or the
      syntenic regions in human genome.

PMID- 23118744
TI  - Cholangiographic features in opium-addicted patients at a tertiary hospital in
      iran.
AB  - Background/Aims. Destructive and metabolic changes in hepatobiliary system have
      been demonstrated following opium use; however, cholangiographic features of bile
      ducts in opium-addicted patients with sphincter of Oddi dysfunction are not
      clearly determined. We described these differences and assessed the effects of
      opium use on postendoscopic retrograde cholangiopancreatography complications.
      Methodology. One hundred and nineteen patients with the diagnosis of sphinctre of
      Oddi dysfunction according to the Geenen-Hogan classification were studied. Eight
      patients were confirmed opium-addicted and others were nonaddicted. Change of
      serum amylase concentrations after endoscopic retrograde cholangiopancreatography
      and clinical diagnosis of addicted and non-addicted patients were compared.
      Results. Serum concentrations of liver aminotransferases and alkaline phosphatase
      were similar between the two groups. Serum concentration of amylase before
      endoscopic retrograde cholangiopancreatography was similar between them, whereas
      concentration of this enzyme was higher in nonaddicted ones after endoscopic
      retrograde cholangiopancreatography. Regarding pathologic changes in papilla,
      opium addiction group in comparison with control group statistically showed more
      tumoral features (25.0% versus 5.4%) and ulcerated changes (12.5% versus 0.0%).
      Conclusions. Opium use can increase probability of papilla ulcerative and tumoral
      changes in patients with sphinctre of Oddi dysfunction. Postendoscopic retrograde
      cholangiopancreatography serum amylase level may be reduced following opium
      addiction.

PMID- 23118745
TI  - Protective effects of methylsulfonylmethane on hemodynamics and oxidative stress
      in monocrotaline-induced pulmonary hypertensive rats.
AB  - Methylsulfonylmethane (MSM) is naturally occurring organic sulfur that is known
      as a potent antioxidant/anti-inflammatory compound. The aim of this study was to
      investigate the effect of MSM on hemodynamics functions and oxidative stress in
      rats with monocrotaline- (MCT-) induced pulmonary arterial hypertension (PAH).
      Wistar rats were randomly assigned to 38-days treatment. MSM was administered to
      rats at 100, 200, and 400 mg/kg/day doses 10 days before a single dose of 60
      mg/kg, IP, MCT. Hemodynamics of ventricles were determined by Powerlab AD
      instrument. Blood samples were obtained to evaluate changes in the antioxidative
      system including activities of catalase (CAT), superoxide dismutase (SOD),
      glutathione peroxidase (GPx), and the level of reduced glutathione (GSH) and
      malondialdehyde (MDA). Improvements in cardiopulmonary hemodynamics were observed
      in the MSM-treated pulmonary arterial hypertensive rats, with a significant
      reduction in right ventricular systolic pressure (RSVP) and an increase in the
      mean arterial pressure (MAP). The values of CAT, SOD, GSH-px activities, and GSH
      were significantly lower in MCT-induced PAH (P < 0.01), but they were recovered
      to control levels of MSM-treated groups. Our present results suggest that long
      term administration of the MSM attenuates MCT-induced PAH in rats through
      modulation of oxidative stress and antioxidant defense.

PMID- 23118746
TI  - The theory and practice of active aging.
AB  - "Active aging" connotes a radically nontraditional paradigm of aging which posits
      possible improvement in health despite increasing longevity. The new paradigm is
      based upon postponing functional declines more than mortality declines and
      compressing morbidity into a shorter period later in life. This paradigm
      (Compression of Morbidity) contrasts with the old, where increasing longevity
      inevitably leads to increasing morbidity. We have focused our research on
      controlled longitudinal studies of aging. The Runners and Community Controls
      study began at age 58 in 1984 and the Health Risk Cohorts study at age 70 in
      1986. We noted that disability was postponed by 14 to 16 years in vigorous
      exercisers compared with controls and postponed by 10 years in low-risk cohorts
      compared with higher risk. Mortality was also postponed, but too few persons had
      died for valid comparison of mortality and morbidity. With the new data presented
      here, age at death at 30% mortality is postponed by 7 years in Runners and age at
      death at 50% (median) mortality by 3.3 years compared to controls. Postponement
      of disability is more than double that of mortality in both studies. These
      differences increase over time, occur in all subgroups, and persist after
      statistical adjustment.

PMID- 23118747
TI  - Emergence and spread of antimicrobial-resistant pathogens in an era of
      globalization.

PMID- 23118749
TI  - Centering Ability and Influence of Experience When Using WaveOne Single-File
      Technique in Simulated Canals.
AB  - Introduction. WaveOne is a single endodontic instrument that reciprocates with a
      dedicated motor to shape root canal systems. The present study assessed the
      centering ability of this simplified protocol along with the effect of experience
      in simulated plastic canals. Methods. One experienced operator shaped two groups
      of simulated canals. Groups 1 and 3 each comprised 30 blinded L-shaped canals or
      S-shaped canals, respectively. Photographs were taken before and after shaping
      and digitally assessed centering after superimposition of the pictures. Time of
      shaping, number of passes, canal aberrations, and instrument degradation were
      recorded. In group 2 shaping was done on 30 blinded L-shaped canals by 30
      different students with no prior experience with WaveOne. Results. All three
      groups yielded satisfactory, reproducible shaping. Centering ratios were low and
      homogeneous in all groups, with no significant differences between the
      experienced operator and the students. Apical transportation values were very low
      (<=0.138 mm) with no instances of blockage or separation. The average shaping
      time was short (43 to 101,6 sec). Conclusions. Within the limits of the study,
      the WaveOne instrument had excellent centering ability with a low risk of
      fracture or blockage and a short shaping time, regardless of the operator's level
      of experience.

PMID- 23118748
TI  - Developments in diagnosis and antileishmanial drugs.
AB  - Leishmaniasis ranks the third in disease burden in disability-adjusted life years
      caused by neglected tropical diseases and is the second cause of parasite-related
      deaths after malaria; but for a variety of reasons, it is not receiving the
      attention that would be justified seeing its importance. Leishmaniasis is a
      diverse group of clinical syndromes caused by protozoan parasites of the genus
      Leishmania. It is estimated that 350 million people are at risk in 88 countries,
      with a global incidence of 1-1.5 million cases of cutaneous and 500,000 cases of
      visceral leishmaniasis. Improvements in diagnostic methods for early case
      detection and latest combitorial chemotherapeutic methods have given a new hope
      for combating this deadly disease. The cell biology of Leishmania and mammalian
      cells differs considerably and this distinctness extends to the biochemical
      level. This provides the promise that many of the parasite's proteins should be
      sufficiently different from hosts and can be successfully exploited as drug
      targets. This paper gives a brief overview of recent developments in the
      diagnosis and approaches in antileishmanial drug discovery and development.

PMID- 23118750
TI  - The principal of dynamic contrast enhanced MRI, the method of pharmacokinetic
      analysis, and its application in the head and neck region.
AB  - Many researchers have established the utility of the dynamic contrast enhanced
      magnetic resonance imaging (DCE-MRI) in the differential diagnosis in the head
      and neck region, especially in the salivary gland tumors. The subjective
      assessment of the pattern of the time-intensity curve (TIC) or the simple
      quantification of the TIC, such as the time to peak enhancement (T(peak)) and the
      wash-out ratio (WR), is commonly used. Although the semiquantitative evaluations
      described above have been widely applied, they do not provide information on the
      underlying pharmacokinetic analysis in tissue. The quantification of DCE-MRI is
      preferable; therefore, many compartment model analyses have been proposed. The
      Toft and Kermode (TK) model is one of the most popular compartment models, which
      provide information about the influx forward volume transfer constant from plasma
      into the extravascular-extracellular space (EES) and the fractional volume of EES
      per unit volume of tissue is used in many clinical studies. This paper will
      introduce the method of pharmacokinetic analysis and also describe the clinical
      application of this technique in the head and neck region.

PMID- 23118751
TI  - Magnetic resonance angiography using fresh blood imaging in oral and
      maxillofacial regions.
AB  - The present paper provides general dentists with an introduction to the clinical
      applications and significance of magnetic resonance angiography (MRA) in the oral
      and maxillofacial regions. Specifically, the method and characteristics of MRA
      are first explained using the relevant MR sequences. Next, clinical applications
      to the oral and maxillofacial regions, such as identification of hemangiomas and
      surrounding vessels by MRA, are discussed. Moreover, the clinical significance of
      MRA for other regions is presented to elucidate future clinical applications of
      MRA in the oral and maxillofacial regions.

PMID- 23118753
TI  - Use of Self-Organizing Map to Analyze Images of Fungi Colonies Grown from
      Triticum aestivum Seeds Disinfected by Ozone Treatment.
AB  - We submitted to ozone treatment Triticum aestivum (common wheat) seeds severely
      contaminated by fungi. Fungi colonies developed when seeds were placed over malt
      agar medium in Petri dishes; Fusarium sp. and Alternaria sp. were identified.
      However, conventional colonies counting did not allow a clear assessment of the
      effect of ozone disinfection. We thus used self-organizing maps (SOMs) to perform
      an image analysis of colonies surface area that clearly showed a significant
      disinfection effect on Fusarium sp.

PMID- 23118752
TI  - In vitro osteogenic properties of two dental implant surfaces.
AB  - Current dental implant research aims at understanding the biological basis for
      successful implant therapy. The aim of the study was to perform a full
      characterization of the effect of two commercial titanium (Ti) surfaces,
      OsseoSpeed and TiOblast, on the behaviour of mouse preosteoblast MC3T3-E1 cells.
      The effect of these Ti surfaces was compared with tissue culture plastic (TCP).
      In vitro experiments were performed to evaluate cytotoxicity, cell morphology and
      proliferation, alkaline phosphatase activity, gene expression, and release of a
      wide array of osteoblast markers. No differences were observed on cell viability
      and cell proliferation. However, changes were observed in cell shape after 2
      days, with a more branched morphology on OsseoSpeed compared to TiOblast.
      Moreover, OsseoSpeed surface increased BMP-2 secretion after 2 days, and this was
      followed by increased IGF-I, BSP, and osterix gene expression and mineralization
      compared to TiOblast after 14 days. As compared to the gold standard TCP, both Ti
      surfaces induced higher osteocalcin and OPG release than TCP and differential
      temporal gene expression of osteogenic markers. The results demonstrate that the
      gain of using OsseoSpeed surface is an improved osteoblast differentiation and
      mineralization, without additional effects on cell viability or proliferation.

PMID- 23118754
TI  - Role of osteoplastic frontal sinus obliteration in the era of endoscopic sinus
      surgery.
AB  - Objective. Determining the indications for osteoplastic frontal sinus
      obliteration (OFSO) for the treatment of inflammatory frontal sinus disease.
      Study Design. Retrospective case series from a single tertiary care facility.
      Methods. Thirty-four patients who underwent OFSO for chronic frontal sinusitis (n
      = 23) and frontal sinus mucocele (n = 11) comprised our study group. Data
      reviewed included demographics, history of prior frontal sinus operation(s),
      imaging, diagnosis, and operative complications. Results. The age range was 19 to
      76 years. Seventy percent of patients with chronic frontal sinusitis underwent
      OFSO as a salvage surgery after previous frontal sinus surgery failures, while
      30% underwent OFSO as a primary surgery. For those in whom OFSO was a salvage
      procedure, the failed surgeries were endoscopic approaches to the frontal sinus
      (69%), Lynch procedure (12%), and OFSO outside this study period (19%). For
      patients with frontal sinus mucocele, 72% had OFSO as a first-line surgery.
      Within the total study population, 15% of patients presented for OFSO with
      history of prior obliteration, with a range of 3 to 30 years between
      representations. Conclusions. Osteoplastic frontal sinus obliteration remains a
      key surgical treatment for chronic inflammatory frontal sinus disease both as a
      salvage procedure and first-line surgical therapy.

PMID- 23118755
TI  - Multidisciplinary service utilization pattern by advanced head and neck cancer
      patients: a single institution study.
AB  - Purpose. To analyze the patterns and associations of adjunctive service visits by
      head and neck cancer patients receiving primary, concurrent chemoradiation
      therapy. Methods. Retrospective chart review of patients receiving adjunctive
      support during a uniform chemoradiation regimen for stages III-IV head and neck
      squamous cell carcinoma. Univariate and multivariate models for each outcome were
      obtained from simple and multivariate linear regression analyses. Results. Fifty
      two consecutive patients were assessed. Female gender, single marital status, and
      nonprivate insurance were factors associated with an increased number of social
      work visits. In a multivariate analysis, female gender and marital status were
      related to increased social work services. Female gender and stage IV disease
      were significant for increased nursing visits. In a multivariate analysis for
      nursing visits, living greater than 20 miles between home and hospital was a
      negative predictive factor. Conclusion. Treatment of advanced stage head and neck
      cancer with concurrent chemoradiation warrants a multidisciplinary approach.
      Female gender, single marital status, and stage IV disease were correlated with
      increased utilization of social work and nursing services. Distance over 20 miles
      from the center was a negative factor. This information may help guide the
      treatment team to allocate resources for the comprehensive care of patients.

PMID- 23118756
TI  - Slow cortical potentials and amplification-part I: n1-p2 measures.
AB  - Slow cortical potentials (SCPs) are currently of great interest in the hearing
      aid fitting process for infants; however, there is conflicting evidence in the
      literature concerning the use of SCPs for this purpose. The current study
      investigated SCP amplitudes and latencies in young normal-hearing listeners in
      response to a 60 ms duration tonal stimulus (1000 Hz) presented at three
      intensities (30, 50, and 70 dB SPL) in aided and unaided conditions using three
      hearing aids (Analog, DigitalA, and DigitalB) with two gain settings (20 and 40
      dB). Results showed that SCP amplitudes were smaller for the digital hearing aids
      compared with the analog hearing aid, and none of the hearing aids resulted in a
      reliable increase in response amplitude relative to the unaided across
      conditions. SCP latencies in analog conditions were not significantly different
      from latencies in the unaided conditions; however, both digital hearing aids
      resulted in significantly delayed SCP latencies. The results of the current study
      (as well as several previous studies) indicate that the SCP may not accurately
      reflect the amplified stimulus expected from the prescribed hearing aids. Thus,
      "aided-SCP" results must be interpreted with caution, and more research is
      required concerning possible clinical use of this technique.

PMID- 23118757
TI  - Is IgG4-Related Disease a Cause of Xerostomia? A Cohort Study of 60 Patients.
AB  - Objective. Immunoglobulin-G4-(IgG4-) related disease (IgG4 RD) is a fibrosing
      process characterized by a significant infiltration of IgG4-secreting plasma
      cells. IgG4 RD can affect almost all organs including salivary glands. Whether
      IgG4 RD plays a role in the development of sicca syndrome and particularly dry
      mouth syndrome remains to be investigated. Methods. We conducted a monocentric
      cohort study for two years to search for IgG4 RD features in patients with dry
      mouth syndrome using immunostainings of labial salivary gland specimens with anti
      IgG4 antibody. Results. Among 60 patients presenting with dry mouth syndrome who
      underwent labial salivary gland biopsy, 18 showed positive immunostaining with
      the anti-IgG4 antibody including 4 patients with typical systemic IgG4 RD. Five
      also fulfilled criteria for Sjogren's syndrome. Conclusion. These findings
      suggest that clinical forms of IgG4 RD salivary involvement without salivary
      swelling may occur. This salivary involvement is probably overlooked in everyday
      practice and could represent a mild form of IgG4 RD.

PMID- 23118758
TI  - Metastasizing pleomorphic adenoma: a fascinating enigma.
AB  - Among salivary gland neoplasms, metastasizing pleomorphic adenoma (MPA)
      constitutes an extremely rare group of tumors. The present paper reports a case
      of pleomorphic adenoma (PA) in submandibular gland that, after more than 30 years
      of initial treatment, recurred and metastasized to ipsilateral neck lymph nodes
      and parotid gland. In an attempt to elucidate the malignant behavior of
      metastasizing pleomorphic adenoma, we performed Ki-67, p53, p16, and bcl-2
      immunohistochemistry staining of our case sample. Many immunohistochemistry
      staining studies have been done on malignant salivary gland tumors. However, to
      the best of our knowledge no immunohistochemistry staining of the aforementioned
      markers has been previously performed on metastasizing pleomorphic adenoma.

PMID- 23118759
TI  - Hair-thread tourniquet syndrome: a case report and literature review.
AB  - Though widely reported, Hair-thread Tourniquet Syndrome (HTTS) is poorly
      recognized. It refers to external, mechanical, circumferential constriction of an
      appendage, typically with an end-artery such as a digit, resulting in a
      "compartment syndrome-like" situation. HTTS is illustrated using the case of an
      infant. Children presenting with irritability should have their digits examined
      for signs of strangulation, with the awareness that numerous strands may be
      involved, with some buried in the skin. Early surgical-release must be performed
      if unwinding or simple cutting is unsuccessful.

PMID- 23118760
TI  - Lichen Simplex Chronicus That Accompanies Anogenital Warts during the Childhood.
AB  - Anogenital warts and lichen simplex chronicus (LSC) are rarely seen during the
      childhood. A 9-year-old girl has been presented to hospital by her parents with
      itching in the anogenital area. There were anogenital warts and a different
      erythematous lesion in the perianal region. On the pulpa of the right thumb,
      there was a wart extending under the nail. The lesions are surgically removed.
      The results of the histopathological examination were reported as condyloma
      acuminata and LSC. Children with anogenital warts should be examined carefully to
      discover the transmission route and other possible concomitant cutaneous
      diseases.

PMID- 23118761
TI  - Transabdominal migration of retained surgical sponge.
AB  - Retained surgical sponge (RSS) is a rare surgical complication. The RSSs are
      mostly located intra-abdominally but they can also be left in the thorax, spine,
      extremity, cranium, and breast. RSS is often difficult to diagnose because of the
      nonspecific clinical symptoms and radiologic findings. Clinically, RSS may
      present as an exudative reaction in the early postoperative period or may also
      cause an aseptic fibrous tissue response. A foreign body may remain
      asymptomatically silent for a long time, and it may later present with
      obstruction, fistulization, or mass formation. In this report, we present a case
      in which an RSS has migrated through the abdominal wall and caused an anterior
      abdominal wall abscess.

PMID- 23118762
TI  - Atrial fibrillation after inhalational lung injury: a troubling complication of a
      rare problem.
AB  - Atrial fibrillation (AF) has been associated with lung diseases like pneumonia
      and chronic obstructive pulmonary disease but has only infrequently been
      associated with inhalational lung injury. We report two cases of resistant AF,
      which developed in young healthy manual laborers shortly after inhalational lung
      injury due to massive quantity of pesticides and anhydrous ammonia, respectively.
      They had no evidence of valvular or structural heart disease and did not have any
      previous medical problems. The AF was resistant to antiarrhythmic drugs and
      required pulmonary vein isolation in first patient and possibly the second
      patient who is currently being evaluated for this procedure. These arrhythmias
      may reflect direct myocardial injury during and after exposure. Alternatively,
      multiple mechanisms can cause atrial fibrillation in lung diseases, including
      hypoxemia, acidemia, inflammatory mediators, and structural changes in the atria
      and ventricle, and these could lead to AF in inhalational lung injury cases. AF
      needs to be excluded when patients present with palpitations after inhalational
      lung injury, especially since, if unrecognized, AF may lead to complications,
      like thromboembolic phenomenon and tachycardiomyopathy.

PMID- 23118763
TI  - Postthyroidectomy Horner's Syndrome.
AB  - Horner's syndrome (HSd) results from an injury along the cervical sympathetic
      chain, producing ipsilateral miosis, ptosis, enophthalmos, and facial anhydrosis.
      Although more commonly associated to malignant tumors affecting the preganglionar
      segment of the sympathetic chain (especially in the lung apex), HSd has been
      described as a rare complication of thyroid surgery. We herein report a case of
      HSd after completing total thyroidectomy.

PMID- 23118764
TI  - An atypical presentation of brucellosis in a patient with isolated
      thrombocytopenia complicated with upper gastrointestinal tract bleeding.
AB  - A 59-year-old female patient was admitted to the emergency service with
      complaints of hematemesis and melena for the last few days. In laboratory tests,
      the platelet count was found to be 6 * 10(9)/L. Intravenous or oral
      corticosteroid treatment was thought to be given for ITP but disclaimed due to
      upper GIS bleeding. On the 5th day of treatment, Brucella melitensis was isolated
      from blood culture before the results of Wright tube agglutination tests were
      reported positive as 1 : 80. On the second day of the anti-brucellosis treatment,
      the thrombocyte count was raised from 6000/mm(3) to 110000/mm(3), and on the 3rd
      day to 225000/mm(3).

PMID- 23118765
TI  - Hepatitis C virus clearance after discontinuation of pegylated interferon alpha
      2a monotherapy in a child.
AB  - The present patient was a 4-year-old boy. His hepatitis C virus genotype was 2a,
      and his viral load was high (1400,000 U/mL). The pretreatment liver biopsy
      revealed no fibrosis or malignancy and mild chronic hepatitis; his Knodell's
      histological activity (HAI) score was 4. Single nucleotide polymorphism of IL28B
      (rs8099917) was major type. The patient began antiviral treatment with pegylated
      interferon alpha 2a (90 MUg/week). At week 9, serum HCV RNA became undetectable,
      with a sensitivity of 50 copies/mL. Antiviral treatment was discontinued at week
      11 because the ALT level increased to 610 U/L. After discontinuation of therapy,
      the patient's serum HCV RNA status became positive again. The serum viral load
      increased to 100,000 U/mL. During this period, he had been observed without
      medication. Sixteen months after stopping treatment, serum HCV became
      undetectable. Over a 4-year period, HCV RNA became negative and his anti-HCV
      antibody titer gradually decreased. In conclusion, though antiviral therapy
      resulted in failure or incomplete therapy, a reduced viral load resulted in viral
      clearance in the present patient. Interleukin 28B genotype might have association
      with the clearance of hepatitis C virus after discontinuation of antiviral
      therapy.

PMID- 23118766
TI  - Portal hypertensive duodenopathy manifesting as "kissing" duodenal ulcers in a
      nigerian with alcoholic cirrhosis: a case report and brief review of the
      literature.
AB  - Multiple duodenal ulcers are an uncommon finding in portal hypertensive
      duodenopathy (PHD). They represent a potential source of clinically significant
      bleeding from the upper gastrointestinal system in patients with cirrhosis. As
      this particular ulcer entity in relation to PHD has no distinguishing symptoms
      aside from those relating to the consequent bleeding, most of them are found
      either on routine endoscopic screening for cirrhotics or on endoscopic
      examination for cause(s) of bleeding in this patient population. The case
      documented below highlights many of the aspects of pathogenesis, associations,
      and consequences of this unique endoscopic finding in cirrhotic patients.

PMID- 23118767
TI  - Nicorandil-induced hyperkalemia in a uremic patient.
AB  - Nicorandil is an antianginal agent with nitrate-like and ATP-sensitive potassium
      channel activator properties. After activation of potassium channels, potassium
      ions are expelled out of the cells, which lead to membrane hyperpolarization,
      closure of voltage-gated calcium channels, and finally vasodilation. We present a
      uremic case suffering from repeated junctional bradycardia, especially before
      hemodialysis. After detailed evaluation, nicorandil was suspected to be the cause
      of hyperkalemia which induced bradycardia. This case reminds us that physicians
      should be aware of this potential complication in patients receiving ATP
      sensitive potassium channel activator.

PMID- 23118768
TI  - Prenatal diagnosis of 17p13.1p13.3 duplication.
AB  - We present here the first prenatal diagnosis of 17p13.1p13.3 duplication. 17p13.3
      duplication has recently been defined as a new distinctive syndrome with several
      diagnosed patients. In the current case prenatal chromosome analysis (G-banding)
      performed on cultured amniocytes revealed additional material in chromosome 19p.
      This was further defined as a chromosome 17p13.1p13.3 duplication by FISH and
      genomic microarray analysis (GMA). In addition Prenatal BACs-on-Beads (PN_BoBs)
      assay was performed, which detected the duplication clearly. This enables rapid
      prenatal diagnosis of the duplication for this family in the future.

PMID- 23118769
TI  - CD34 Expression in the Stromal Cells of Alveolar Adenoma.
AB  - The alveolar adenoma of the lung is a rare benign tumor characterized by a
      proliferation of both the alveolar epithelial cells and the mesenchymal septal
      cells. Immunohistochemically, the epithelial cells stain for cytokeratin (CK)
      AE1AE3, CK7, thyroid transcription factor 1 (TTF1), and surfactant apoprotein
      confirming the derivation by the type 2 pneumocytes. The stromal cells are
      negative for these markers but they show focally smooth muscle and muscle
      specific actin positivity. We describe two cases that showed
      immunohistochemically a CD34 positivity of the mesenchymal septal cells. This
      aspect has been previously described in a two cases report, but not emphasized by
      the authors as a distinctive feature of the lesion. We consider this CD34
      positivity as a marker of immaturity or stemness of the lesional septal spindle
      cells, that could be responsible of the different phenotypic and morphological
      profile of the interstitial cells, that could be, therefore, considered
      neoplastic and not reactive.

PMID- 23118770
TI  - Long-term remission of primary bone marrow diffuse large B-cell lymphoma treated
      with high-dose chemotherapy rescued by in vivo rituximab-purged autologous stem
      cells.
AB  - Primary bone marrow diffuse large B-cell lymphoma (DLBCL) is a rare type of
      extranodal lymphoma with poor prognosis. Here, we report a case of primary bone
      marrow DLBCL successfully treated with high-dose chemotherapy and rescued by in
      vivo rituximab-purged autologous stem cells. A 39-year-old woman visited our
      hospital because of anemia. Bone marrow examination revealed a large B-cell
      lymphoma invasion. An (18)F-fluorodeoxyglucose positron emission tomography scan
      revealed disseminated bone marrow uptake without evidence of dissemination at
      other sites. These findings led to a diagnosis of primary bone marrow DLBCL. Our
      patient underwent R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine,
      and prednisolone) chemotherapy and achieved complete remission. Subsequently, she
      received high-dose chemotherapy with an in vivo rituximab-purged autologous stem
      cell transplant. Seven years have passed since the transplantation, and she
      remains in remission. This suggests that transplantation of an in vivo rituximab
      purged autograft is a promising strategy for primary bone marrow DLBCL.

PMID- 23118771
TI  - The Effectiveness of School-Based Nutritional Education Program among Obese
      Adolescents: A Randomized Controlled Study.
AB  - The purpose of the study was to determine the change in body weight and body mass
      index (BMI), as well as diet behaviors at 4 months after intervention between
      obese adolescent girls who participated in the school-based nutritional education
      program, addressed by pediatrician, compared to those who attended regular
      nutritional class. Methods. 49 obese girls were recruited from a secondary
      school. Those, were randomized into 2 groups of intervention and control. The
      intensive interactive nutritional program was provided to the intervention group.
      Weight and height, dietary record and % fat consumption, as well as self
      administered questionnaires on healthy diet attitudes were collected at baseline
      and 4-month follow-up, and then compared between two groups. Results. There was a
      statistically significant change of BMI in the intervention group by 0.53 +/-
      1.16 kg/m(2) (P = 0.016) compared to the control group (0.51 +/- 1.57 kg/m(2), P
      = 0.063) but no significant change in calorie and % fat consumption between
      groups. The attitudes on healthy eating behaviors in the intervention group were
      shown improving significantly (P < 0.001). Conclusions. Interactive and intensive
      nutritional education program as shown in the study was one of the most
      successful school-based interventions for obese adolescents.

PMID- 23118772
TI  - Large Scale Solid Phase Synthesis of Peptide Drugs: Use of Commercial Anion
      Exchange Resin as Quenching Agent for Removal of Iodine during Disulphide Bond
      Formation.
AB  - The S-acetamidomethyl (Acm) or trityl (Trt) protecting groups are widely used in
      the chemical synthesis of peptides that contain one or more disulfide bonds.
      Treatment of peptides containing S-Acm protecting group with iodine results in
      simultaneous removal of the sulfhydryl protecting group and disulfide formation.
      However, the excess iodine needs to be quenched or adsorbed as quickly as
      possible after completion of the disulfide bond formation in order to minimize
      side reactions that are often associated with the iodination step. We report here
      a simple method for simultaneous quenching and removal of iodine and isolation of
      disulphide bridge peptides. The use of excess inexpensive anion exchange resin to
      the oxidized peptide from the aqueous acetic acid/methanol solution affords
      quantitative removal of iodine and other color impurities. This improves the
      resin life time of expensive chromatography media that is used in preparative
      HPLC column during the purification of peptide using preparative HPLC. Further,
      it is very useful for the conversion of TFA salt to acetate in situ. It was
      successfully applied commercially, to the large scale synthesis of various
      peptides including Desmopressin, Oxytocin, and Octreotide. This new approach
      offers significant advantages such as more simple utility, minimal side
      reactions, large scale synthesis of peptide drugs, and greater cost
      effectiveness.

PMID- 23118773
TI  - Diet-induced obesity in mice overexpressing neuropeptide y in noradrenergic
      neurons.
AB  - Neuropeptide Y (NPY) is a neurotransmitter associated with feeding and obesity.
      We have constructed an NPY transgenic mouse model (OE-NPY(DBH) mouse), where
      targeted overexpression leads to increased levels of NPY in noradrenergic and
      adrenergic neurons. We previously showed that these mice become obese on a normal
      chow. Now we aimed to study the effect of a Western-type diet in OE-NPY(DBH) and
      wildtype (WT) mice, and to compare the genotype differences in the development of
      obesity, insulin resistance, and diabetes. Weight gain, glucose, and insulin
      tolerance tests, fasted plasma insulin, and cholesterol levels were assayed. We
      found that female OE-NPY(DBH) mice gained significantly more weight without
      hyperphagia or decreased activity, and showed larger white and brown fat depots
      with no difference in UCP-1 levels. They also displayed impaired glucose
      tolerance and decreased insulin sensitivity. OE-NPY(DBH) and WT males gained
      weight robustly, but no difference in the degree of adiposity was observed.
      However, 40% of OE-NPY(DBH) but none of the WT males developed hyperglycaemia
      while on the diet. The present study shows that female OE-NPY(DBH) mice were not
      protected from the obesogenic effect of the diet suggesting that increased NPY
      release may predispose females to a greater risk of weight gain under high
      caloric conditions.

PMID- 23118774
TI  - Airway Smooth Muscle Dynamics and Hyperresponsiveness: In and outside the Clinic.
AB  - The primary functional abnormality in asthma is airway hyperresponsiveness (AHR)
      excessive airway narrowing to bronchoconstrictor stimuli. Our understanding of
      the underlying mechanism(s) producing AHR is incomplete. While structure-function
      relationships have been evoked to explain AHR (e.g., increased airway smooth
      muscle (ASM) mass in asthma) more recently there has been a focus on how the
      dynamic mechanical environment of the lung impacts airway responsiveness in
      health and disease. The effects of breathing movements such as deep inspiration
      reveal innate protective mechanisms in healthy individuals that are likely
      mediated by dynamic ASM stretch but which may be impaired in asthmatic patients
      and thereby facilitate AHR. This perspective considers the evidence for and
      against a role of dynamic ASM stretch in limiting the capacity of airways to
      narrow excessively. We propose that lung function measured after bronchial
      provocation in the laboratory and changes in lung function perceived by the
      patient in everyday life may be quite different in their dependence on dynamic
      ASM stretch.

PMID- 23118775
TI  - Sublingual Immunotherapy Induces Regulatory Function of IL-10-Expressing
      CD4(+)CD25(+)Foxp3(+) T Cells of Cervical Lymph Nodes in Murine Allergic Rhinitis
      Model.
AB  - Sublingual immunotherapy (SLIT) has been considered to be a painless and
      efficacious therapeutic treatment of allergic rhinitis which is known as type I
      allergy of nasal mucosa. Nevertheless, its mechanisms need to be further
      investigated. In this study, we constructed an effective murine model of
      sublingual immunotherapy in allergic rhinitis, in which mice were sublingually
      administered with ovalbumin (OVA) followed by intraperitoneal sensitization and
      nasal challenge of OVA. Sublingually treated mice showed significantly decreased
      specific IgE responses as well as suppressed Th2 immune responses. Sublingual
      administration of OVA did not alter the frequency of CD4(+)CD25(+) regulatory T
      cells (Tregs), but led to upregulation of Foxp3- and IL-10-specific mRNAs in the
      Tregs of cervical lymph nodes (CLN), which strongly suppressed Th2 cytokine
      production from CD4(+)CD25(-) effector T cells in vitro. Furthermore, sublingual
      administration of plasmids encoding the lymphoid chemokines CCL19 and CCL21-Ser
      DNA together with OVA suppressed allergic responses. These results suggest that
      IL-10-expressing CD4(+)CD25(+)Foxp3(+) Tregs in CLN are involved in the
      suppression of allergic responses and that CCL19/CCL21 may contribute to it in
      mice that received SLIT.

PMID- 23118776
TI  - A Brief History of Airway Smooth Muscle's Role in Airway Hyperresponsiveness.
AB  - A link between airway smooth muscle (ASM) and airway hyperresponsiveness (AHR) in
      asthma was first postulated in the midnineteenth century, and the suspected link
      has garnered ever increasing interest over the years. AHR is characterized by
      excessive narrowing of airways in response to nonspecific stimuli, and it is the
      ASM that drives this narrowing. The stimuli that can be used to demonstrate AHR
      vary widely, as do the potential mechanisms by which phenotypic changes in ASM or
      nonmuscle factors can contribute to AHR. In this paper, we review the history of
      research on airway smooth muscle's role in airway hyperresponsiveness. This
      research has ranged from analyzing the quantity of ASM in the airways to testing
      for alterations in the plastic behavior of smooth muscle, which distinguishes it
      from skeletal and cardiac muscles. This long history of research and the
      continued interest in this topic mean that the precise role of ASM in airway
      responsiveness remains elusive, which makes it a pertinent topic for this
      collection of articles.

PMID- 23118777
TI  - Dendritic cells, viruses, and the development of atopic disease.
AB  - Dendritic cells are important residents of the lung environment. They have been
      associated with asthma and other inflammatory diseases of the airways. In
      addition to their antigen-presenting functions, dendritic cells have the ability
      to modulate the lung environment to promote atopic disease. While it has long
      been known that respiratory viral infections associate with the development and
      exacerbation of atopic diseases, the exact mechanisms have been unclear. Recent
      studies have begun to show the critical importance of the dendritic cell in this
      process. This paper focuses on these data demonstrating how different populations
      of dendritic cells are capable of bridging the adaptive and innate immune
      systems, ultimately leading to the translation of viral illness into atopic
      disease.

PMID- 23118778
TI  - Improving the safety of tolerance induction: chimerism and cellular co-treatment
      strategies applied to vascularized composite allografts.
AB  - Although vascularized composite allografts (VCAs) have been performed clinically
      for a variety of indications, potential complications from long-term
      immunosuppression and graft-versus-host disease remain important barriers to
      widespread applications. Recently it has been demonstrated that VCAs
      incorporating a vascularized long bone in a rat model provide concurrent
      vascularized bone marrow transplantation that, itself, functions to establish
      hematopoietic chimerism and donor-specific tolerance following non-myeloablative
      conditioning of recipients. Advances such as this, which aim to improve the
      safety profile of tolerance induction, will help usher in an era of wider
      clinical VCA application for nonlife-saving reconstructions.

PMID- 23118780
TI  - Ileal inflammation may trigger the development of GP2-specific pancreatic
      autoantibodies in patients with Crohn's disease.
AB  - Why zymogen glycoprotein 2 (GP2), the Crohn's disease (CD)-specific pancreatic
      autoantigen, is the major target of humoral autoimmunity in inflammatory bowel
      diseases (IBD) is uknown. Recent evidence demonstrates that GP2 is also present
      on the apical surface of microfold (M) intestinal cells. As the colon lacks GP2
      rich M cells, we assumed that patients with colonic CD are seronegative for anti
      GP2. Anti-GP2 antibodies were tested in 225 CDs, including 45 patients with
      colonic location (L2), 45 with terminal ileum (L1) and 135 with ileocolonic
      involvement; 225 patients with ulcerative colitis (UC) were also tested. Anti-GP2
      reactivity was detected in 59 (26.2%) CDs and 15 (6.7%) UCs (P < 0.001). Only 5
      CDs with L2 had anti-GP2 antibodies, compared to 54/180 (30.0%, P = 0.0128) of
      the CDs with L1 and L3. Anti-GP2 antibody positive CD patients had higher ASCA
      titres compared to seronegative cases. Amongst the 128 CD patients with previous
      surgical intervention, 45 (35.0%) were anti-GP2 antibody positive compared to
      14/97 (14.0%) without surgical (P < 0.001). Our data support the assumption that
      ileal inflammation is required for the development of anti-GP2 antibodies in CD,
      and suggest that the intestine rather than the pancreatic juice is the antigenic
      source required for the initiation of anti-GP2 antibodies.

PMID- 23118779
TI  - Initiation and regulation of complement during hemolytic transfusion reactions.
AB  - Hemolytic transfusion reactions represent one of the most common causes of
      transfusion-related mortality. Although many factors influence hemolytic
      transfusion reactions, complement activation represents one of the most common
      features associated with fatality. In this paper we will focus on the role of
      complement in initiating and regulating hemolytic transfusion reactions and will
      discuss potential strategies aimed at mitigating or favorably modulating
      complement during incompatible red blood cell transfusions.

PMID- 23118781
TI  - Invariant NKT cells as novel targets for immunotherapy in solid tumors.
AB  - Natural killer T (NKT) cells are a small population of lymphocytes that possess
      characteristics of both innate and adaptive immune cells. They are uniquely
      poised to respond rapidly to infection and inflammation and produce cytokines
      that critically shape the ensuing adaptive cellular response. Therefore, they
      represent promising therapeutic targets. In cancer, NKT cells are attributed a
      role in immunosurveillance. NKT cells also act as potent activators of antitumor
      immunity when stimulated with a synthetic agonist in experimental models.
      However, in some settings, NKT cells seem to act as suppressors and regulators of
      antitumor immunity. Here we briefly review current data supporting these
      paradoxical roles of NKT cells and their regulation. Increased understanding of
      the signals that determine the function of NKT cells in cancer will be essential
      to improve current strategies for NKT-cell-based immunotherapeutic approaches.

PMID- 23118783
TI  - Understanding the molecular mechanism of interventions in treating rheumatoid
      arthritis patients with corresponding traditional chinese medicine patterns based
      on bioinformatics approach.
AB  - Better effectiveness would be achieved when interventions are used in treating
      patients with a specific traditional Chinese medicine (TCM) pattern. In this
      paper, the effectiveness in treating rheumatoid arthritis (RA) patients in a
      randomized clinical trial as reanalyzed after the patients were classified into
      different TCM patterns and the underlying mechanism of how the TCM pattern
      influences the clinical effectiveness of interventions (TCM and biomedicine
      therapy) was explored. The pharmacological networks of interventions were builtup
      with protein and protein interaction analyses based on all the related targeted
      proteins obtained from PubChem. The underlying mechanism was explored by merging
      the pharmacological networks with the molecular networks of TCM cold and hot
      patterns in RA. The results show that the TCM therapy is better in treating the
      RA patients with TCM hot pattern, and the biomedical therapy is better in the RA
      patients with cold pattern. The pharmacological network of TCM intervention is
      merged well with the molecular network of TCM hot pattern, and the
      pharmacological network of biomedical therapy is merged well with the network of
      cold pattern. The finding indicates that molecular network analysis could give
      insight into the full understanding of the underlying mechanism of how TCM
      pattern impacts the efficacy.

PMID- 23118782
TI  - Tumor-induced CD8+ T-cell dysfunction in lung cancer patients.
AB  - Lung cancer is the leading cause of cancer deaths worldwide and one of the most
      common types of cancers. The limited success of chemotherapy and radiotherapy
      regimes have highlighted the need to develop new therapies like antitumor
      immunotherapy. CD8+ T-cells represent a major arm of the cell-mediated anti-tumor
      response and a promising target for developing T-cell-based immunotherapies
      against lung cancer. Lung tumors, however, have been considered to possess poor
      immunogenicity; even so, lung tumor-specific CD8+ T-cell clones can be
      established that possess cytotoxicity against autologous tumor cells. This paper
      will focus on the alterations induced in CD8+ T-cells by lung cancer. Although
      memory CD8+ T-cells infiltrate lung tumors, in both tumor-infiltrating
      lymphocytes (TILs) and malignant pleural effusions, these cells are dysfunctional
      and the effector subset is reduced. We propose that chronic presence of lung
      tumors induces dysfunctions in CD8+ T-cells and sensitizes them to activation
      induced cell death, which may be associated with the poor clinical responses
      observed in immunotherapeutic trials. Getting a deeper knowledge of the evasion
      mechanisms lung cancer induce in CD8+ T-cells should lead to further
      understanding of lung cancer biology, overcome tumor evasion mechanisms, and
      design improved immunotherapeutic treatments for lung cancer.

PMID- 23118784
TI  - Effects of Vitamin D Supplementation during the Induction and Progression of
      Osteoarthritis in a Rat Model.
AB  - Epidemiological studies correlate low levels of vitamin D with the osteoarthritis
      (OA) progression. Cytokines and metalloproteases play a major role in OA
      promoting the inflammation and degradation of the cartilage and can be induced
      through the Toll-like receptor (TLR) pathway. The aim of this study was to
      evaluate the protective effect of vitamin D supplementation on the development of
      osteoarthritis (OA) through examining the genetic regulation of TLRs, cytokines,
      and metalloproteases in chondrocytes as well as the wideness of cartilage in rats
      with OA. Our results demonstrate that the signaling through TLR-4 is a
      proinflammatory mechanism in osteoarthritis that drives the upregulation of MMP
      3, IL-1beta, and TNF-alpha gene expression, leading to cartilage degradation and
      inflammation. Vitamin D supplementation had a protective effect during the onset
      but not during the chronic stage of OA in the rat model.

PMID- 23118785
TI  - Two different isomers of vitamin e prevent bone loss in postmenopausal
      osteoporosis rat model.
AB  - Postmenopausal osteoporotic bone loss occurs mainly due to cessation of ovarian
      function, a condition associated with increased free radicals. Vitamin E, a lipid
      soluble vitamin, is a potent antioxidant which can scavenge free radicals in the
      body. In this study, we investigated the effects of alpha-tocopherol and pure
      tocotrienol on bone microarchitecture and cellular parameters in ovariectomized
      rats. Three-month-old female Wistar rats were randomly divided into
      ovariectomized control, sham-operated, and ovariectomized rats treated with
      either alpha-tocopherol or tocotrienol. Their femurs were taken at the end of the
      four-week study period for bone histomorphometric analysis. Ovariectomy causes
      bone loss in the control group as shown by reduction in both trabecular volume
      (BV/TV) and trabecular number (Tb.N) and an increase in trabecular separation
      (Tb.S). The increase in osteoclast surface (Oc.S) and osteoblast surface (Ob.S)
      in ovariectomy indicates an increase in bone turnover rate. Treatment with either
      alpha-tocopherol or tocotrienol prevents the reduction in BV/TV and Tb.N as well
      as the increase in Tb.S, while reducing the Oc.S and increasing the Ob.S. In
      conclusion, the two forms of vitamin E were able to prevent bone loss due to
      ovariectomy. Both tocotrienol and alpha-tocopherol exert similar effects in
      preserving bone microarchitecture in estrogen-deficient rat model.

PMID- 23118786
TI  - Vitamin e and bone structural changes: an evidence-based review.
AB  - Purpose. This paper explores the effects of vitamin E on bone structural changes.
      Methods. A systematic review of the literature was conducted to identify relevant
      studies about vitamin E and osteoporosis/bone structural changes. A comprehensive
      search in Medline and CINAHL for relevant studies published between the years
      1946 and 2012 was conducted. The main inclusion criteria were published in
      English, studies had to report the association or effect of vitamin E and
      osteoporosis-related bone changes, and the osteoporosis-related bone changes
      should be related to lifestyle variables, aging, or experimentally-induced
      conditions. Results. The literature search identified 561 potentially relevant
      articles, whereby 11 studies met the inclusion criteria. There were three human
      epidemiological studies and eight animal experimental studies included in this
      paper. Four animal studies reported positive bone structural changes with vitamin
      E supplementation. The rest of the studies had negative changes or no effect.
      Studies with positive changes reported better effects with tocotrienol vitamin E
      isomer supplementation. Conclusions. This evidence-based review underscores the
      potential of vitamin E being used for osteoporosis. The effect of one of the
      vitamin E isomers, tocotrienols, on bone structural changes warrants further
      exploration. Controlled human observational studies should be conducted to
      provide stronger evidence.

PMID- 23118788
TI  - Therapeutic approaches to neuroprotective activity by complementary and
      alternative medicines.

PMID- 23118787
TI  - Systems biology of meridians, acupoints, and chinese herbs in disease.
AB  - Meridians, acupoints, and Chinese herbs are important components of traditional
      Chinese medicine (TCM). They have been used for disease treatment and prevention
      and as alternative and complementary therapies. Systems biology integrates omics
      data, such as transcriptional, proteomic, and metabolomics data, in order to
      obtain a more global and complete picture of biological activity. To further
      understand the existence and functions of the three components above, we reviewed
      relevant research in the systems biology literature and found many recent studies
      that indicate the value of acupuncture and Chinese herbs. Acupuncture is useful
      in pain moderation and relieves various symptoms arising from acute spinal cord
      injury and acute ischemic stroke. Moreover, Chinese herbal extracts have been
      linked to wound repair, the alleviation of postmenopausal osteoporosis severity,
      and anti-tumor effects, among others. Different acupoints, variations in
      treatment duration, and herbal extracts can be used to alleviate various symptoms
      and conditions and to regulate biological pathways by altering gene and protein
      expression. Our paper demonstrates how systems biology has helped to establish a
      platform for investigating the efficacy of TCM in treating different diseases and
      improving treatment strategies.

PMID- 23118789
TI  - Drug-Drug Interactions Potential of Icariin and Its Intestinal Metabolites via
      Inhibition of Intestinal UDP-Glucuronosyltransferases.
AB  - Icariin is known as an indicative constituent of the Epimedium genus, which has
      been commonly used in Chinese herbal medicine to enhance treat impotence and
      improve sexual function, as well as for several other indications for over 2000
      years. In this study, we aimed to investigate the effects of icariin and its
      intestinal metabolites on the activities of human UDP-glucuronosyltransferase
      (UGT) activities. Using a panel of recombinant human UGT isoforms, we found that
      icariin exhibited potent inhibition against UGT1A3. It is interesting that the
      intestinal metabolites of icariin exhibited a different inhibition profile
      compared with icariin. Different from icariin, icariside II was a potent
      inhibitor of UGT1A4, UGT1A7, UGT1A9, and UGT2B7, and icaritin was a potent
      inhibitor of UGT1A7 and UGT1A9. The potential for drug interactions in vivo was
      also quantitatively predicted and compared. The quantitative prediction of risks
      indicated that in vivo inhibition against intestinal UGT1A3, UGT1A4, and UGT1A7
      would likely occur after oral administration of icariin products.

PMID- 23118790
TI  - Protective effects of the traditional herbal formula oryeongsan water extract on
      ethanol-induced acute gastric mucosal injury in rats.
AB  - This study was performed to evaluate the protective effect and safety of
      Oryeongsan water extract (OSWE) on ethanol-induced acute gastric mucosal injury
      and an acute toxicity study in rats. Acute gastric lesions were induced via
      intragastric oral administration of absolute ethanol at a dose of 5 mL/kg. OSWE
      (100 and 200 mg/kg) was administered to rats 2 h prior to the oral administration
      of absolute ethanol. The stomach of animal models was opened and gastric mucosal
      lesions were examined. Gastric mucosal injuries were evaluated by measuring the
      levels of malondialdehyde (MDA), glutathione (GSH), and the activity of
      antioxidant enzymes. In the acute toxicity study, no adverse effects of OSWE were
      observed at doses up to 2000 mg/kg/day. Administration of OSWE reduced the damage
      by conditioning the gastric mucosa against ethanol-induced acute gastric injury,
      which included hemorrhage, hyperemia, and loss of epithelial cells. The level of
      MDA was reduced in OSWE-treated groups compared with the ethanol-induced group.
      Moreover, the level of GSH and the activity of antioxidant enzymes were
      significantly increased in the OSWE-treated groups. Our findings suggest that
      OSWE has a protective effect on the gastric mucosa against ethanol-induced acute
      gastric injury via the upregulation of antioxidant enzymes.

PMID- 23118791
TI  - NMDA Receptor-Dependent Synaptic Activity in Dorsal Motor Nucleus of Vagus
      Mediates the Enhancement of Gastric Motility by Stimulating ST36.
AB  - Previous studies have demonstrated the efficacy of electroacupuncture at ST36 for
      patients with gastrointestinal motility disorders. While several lines of
      evidence suggest that the effect may involve vagal reflex, the precise molecular
      mechanism underlying this process still remains unclear. Here we report that the
      intragastric pressure increase induced by low frequency electric stimulation at
      ST36 was blocked by AP-5, an antagonist of N-methyl-D-aspartate receptors
      (NMDARs). Indeed, stimulating ST36 enhanced NMDAR-mediated, but not 2-amino-3-(5
      methyl-3-oxo-1,2-oxazol-4-yl)propanoic-acid-(AMPA-) receptor-(AMPAR-) mediated
      synaptic transmission in gastric-projecting neurons of the dorsal motor nucleus
      of the vagus (DMV). We also identified that suppression of presynaptic MU-opioid
      receptors may contribute to upregulation of NMDAR-mediated synaptic transmission
      induced by electroacupuncture at ST36. Furthermore, we determined that the
      glutamate-receptor-2a-(NR2A-) containing NMDARs are essential for NMDAR-mediated
      enhancement of gastric motility caused by stimulating ST36. Taken together, our
      results reveal an important role of NMDA receptors in mediating enhancement of
      gastric motility induced by stimulating ST36.

PMID- 23118792
TI  - Evaluation of the effect of laser acupuncture and cupping with ryodoraku and
      visual analog scale on low back pain.
AB  - The purpose of this study was to evaluate the effect of laser acupuncture (LA)
      and soft cupping on low back pain. In this study, the subjects were randomly
      assigned to two groups: active group (real LA and soft cupping) and placebo group
      (sham laser and soft cupping). Visual analog scale (VAS) and Ryodoraku were used
      to evaluate the effect of treatment on low back pain in this trial. Laser, 40 mW,
      wavelength 808 nm, pulse rate 20 Hz, was used to irradiate Weizhong (BL40) and
      Ashi acupoints for 10 minutes. And the Ryodoraku values were measured 2 times,
      that is, before and 15 minutes after treatment. The results show that there were
      significant difference between the first day baseline and the fifth day treatment
      in VAS in the two groups. Therefore, LA combined with soft cupping or only soft
      cupping was effective on low back pain. However, the Ryodoraku values of Bladder
      Meridian of the placebo group have been decreased apparently, and didn't come
      back to their original values. It means that "cupping" plays the role of "leak or
      purge" in traditional Chinese medicine (TCM). On the other hand, the Ryodoraku
      values of Bladder Meridian of the active group have been turned back to almost
      their original values; "mend or reinforcing" effect is attributed to the laser
      radiation.

PMID- 23118793
TI  - Berberine in the treatment of type 2 diabetes mellitus: a systemic review and
      meta-analysis.
AB  - Objectives. To assess the efficacy and safety of berberine in the treatment of
      type 2 diabetes mellitus (T2DM). Methods. Randomized trials of berberine compared
      with lifestyle modification, placebo, and/or oral hypoglycaemics intervention on
      treating T2DM were included. Study population characteristics and outcome results
      were extracted independently by two reviewers. Meta-analyses were performed for
      data available. Results. Fourteen randomized trials, involving 1068 participants,
      were included in this study. Methodological quality was generally low. Compared
      with lifestyle modification with or without placebo, the cointervention of
      berberine and lifestyle modification showed significantly hypoglycaemic and
      antidyslipidemic response. Compared with oral hypoglycaemics including metformin,
      glipizide, or rosiglitazone, berberine did not demonstrate a significantly better
      glycaemic control but showed a mild antidyslipidemic effect. Compared with oral
      hypoglycaemic drugs, cointerventions with berberine and the same oral
      hypoglycaemics showed a better glycaemic control. No serious adverse effects from
      berberine were reported. Conclusions. Berberine appeared to be efficacious for
      treating hyperglycaemia and dyslipidemia in T2DM. However, the evidence of
      berberine for treating T2DM should be carefully interpreted due to the low
      methodological quality, small sample size, limited number of trials, and
      unidentified risks of bias.

PMID- 23118794
TI  - Use of chinese medicine and subsequent surgery in women with uterine fibroid: a
      retrospective cohort study.
AB  - Background. Chinese medicine (CM) has been used to relieve symptoms relevant to
      uterine fibroids. Objective. This study investigated the association between the
      use of CM and the incidence of uterine surgery in women with uterine fibroids.
      Subjects and Methods. This retrospective cohort study extracted records for
      16,690 subjects diagnosed with a uterine fibroid between 2000 and 2003 from the
      National Health Insurance reimbursement database. The risk factors for surgery
      were examined via Cox proportional hazard analysis, and the difference in
      incidence of surgery between CM users and nonusers was compared using incidence
      rate ratios (IRRs) derived from Poisson's models. Results. After an average
      follow-up period of 4.5 years, the cumulative incidence of uterine surgery was
      significantly lower in CM users than CM nonusers (P < 0.0001). Compared to CM
      nonusers, CM users were more unlikely to undergo uterine surgery (adjusted hazard
      ratio = 0.18, 95% confidence interval (CI) = 0.17, 0.19). The incidence of
      surgery in CM users was dramatically different from that for CM nonusers (IRR =
      0.17, 95% CI = 0.16, 0.18). Conclusion. The risk of uterine surgery among fibroid
      patients who used CM was significantly decreased, implying an effective treatment
      of fibroid-related symptoms provided by CM.

PMID- 23118795
TI  - A herbal composition of semen hoveniae, radix puerariae, and fructus schisandrae
      shows potent protective effects on acute alcoholic intoxication in rodent models.
AB  - This study is designed to evaluate the effects of a herbal composition of Semen
      Hoveniae, Radix Puerariae and Fructus Schisandrae (SRF) against acute alcoholic
      intoxication. The animals were treated with SRF extract (SRFE) for 14 days, and
      ethanol was conducted subsequent to the final treatment. The effects of SRFE on
      righting reflex, inebriety rates, kinetic parameters of blood ethanol and
      acetaldehyde were determined. In addition; levels of alcohol dehydrogenase (ADH)
      and aldehyde dehydrogenase (ALDH), the activities of cytochrome P450 2E1
      (CYP2E1), selected antioxidative enzymes, and the contents of malonaldehyde (MDA)
      were measured. SRFE-pretreated rodents exhibited lower rates of intoxication,
      longer times to loss of righting reflex, and shortened times to recovery of
      righting reflex than in controls. The peak concentrations and area under the time
      concentration curves were lower in the pretreated animals than in controls, which
      corresponded to higher levels of ADH and ALDH in both gastrointestines and livers
      of the SRFE-treated animals. The activities of CYP2E1 were lower in SRFE
      pretreated animals, which also exhibited higher activities of some antioxidant
      enzymes and lower hepatic MDA levels. These findings suggest that the anti
      inebriation effects of SRFE may involve inhibition of ethanol absorption,
      promotion of ethanol metabolism, and enhancing hepatic anti-oxidative functions.

PMID- 23118796
TI  - Shikonin directly targets mitochondria and causes mitochondrial dysfunction in
      cancer cells.
AB  - Chemotherapy is a mainstay of cancer treatment. Due to increased drug resistance
      and the severe side effects of currently used therapeutics, new candidate
      compounds are required for improvement of therapy success. Shikonin, a natural
      naphthoquinone, was used in traditional Chinese medicine for the treatment of
      different inflammatory diseases and recent studies revealed the anticancer
      activities of shikonin. We found that shikonin has strong cytotoxic effects on 15
      cancer cell lines, including multidrug-resistant cell lines. Transcriptome-wide
      mRNA expression studies showed that shikonin induced genetic pathways regulating
      cell cycle, mitochondrial function, levels of reactive oxygen species, and
      cytoskeletal formation. Taking advantage of the inherent fluorescence of
      shikonin, we analyzed its uptake and distribution in live cells with high spatial
      and temporal resolution using flow cytometry and confocal microscopy. Shikonin
      was specifically accumulated in the mitochondria, and this accumulation was
      associated with a shikonin-dependent deregulation of cellular Ca(2+) and ROS
      levels. This deregulation led to a breakdown of the mitochondrial membrane
      potential, dysfunction of microtubules, cell-cycle arrest, and ultimately
      induction of apoptosis. Seeing as both the metabolism and the structure of
      mitochondria show marked differences between cancer cells and normal cells,
      shikonin is a promising candidate for the next generation of chemotherapy.

PMID- 23118797
TI  - Salvianolic Acid B reducing portal hypertension depends on macrophages in
      isolated portal perfused rat livers with chronic hepatitis.
AB  - This study is aimed to investigate the effects of Sal B on portal hypertension
      (PH). PH with chronic hepatitis was induced by carbon tetrachloride (CCl(4)) in
      rats. The model was confirmed with elevated portal pressures and increased serum
      CD163 levels. The inducible nitric oxide synthase (iNOS) or heme oxygenase-1 (HO
      1) in portal triads was assessed. The isolated portal perfused rat liver (IPPRL)
      was performed at d(0), d(28), d(56) , and d(84) in the progression of chronic
      hepatitis. After constricting with phenylephrine, the portal veins were relaxed
      with Sal B. The EC(50) of Sal B for relaxing portal veins was -2.04 * 10(-9),
      7.28 * 10(-11), 1.52 * 10(-11), and 8.44 * 10(-11) mol/L at d(0), d(28), d(56),
      and d(84), respectively. More macrophages infiltrated in portal triads and
      expressed more iNOS or HO-1 as PH advanced. The areas under the curve (AUCs) of
      Sal B for reducing PH were positively correlated with the levels of iNOS or HO-1
      in portal triads, and so did with serum CD163 levels. Sal B reduces PH in IPPRL
      with chronic hepatitis, via promoting portal relaxation due to macrophage
      originated NO or CO in portal triads, partly at least.

PMID- 23118798
TI  - Karyotype and DNA-Methylation Responses in Myelodysplastic Syndromes following
      Treatment with Traditional Chinese Formula Containing Arsenic.
AB  - We have previously shown that arsenic-containing Chinese herbal formula, Qing
      Huang powder capsule (containing tetraarsenic tetrasulfide, As(4)S(4)), is
      effective in the treatment of myelodysplastic syndrome (MDS); yet the underlined
      mechanisms remain unclear. In this study, using standard cytogenetic analysis (G
      banded) and global DNA methylation method (ChIP-on-chip assays), we aimed to
      determine the effect of arsenic-containing Chinese herbal formula on karyotype
      status and the genomic methylation level in primarily diagnosed MDS patients.
      Correlation of aberrant DNA methylation and chromosome aberrations in MDS was
      also investigated. We found that the number of genes with aberrant DNA
      methylation was highest in MDS patients with normal karyotype, followed by
      trisomy 8 karyotype, and relatively low in patients with cytogenetic
      abnormalities other than trisomy 8. Treatment with arsenic-containing Chinese
      herbal formula had no effects on karyotype status, but resulted in a significant
      genome-wide demethylation. Our research uncovered a DNA demethylating activity of
      arsenic-containing Chinese herbal formula in the treatment of MDS.

PMID- 23118799
TI  - Redundancy as a graph-based index of frequency specific MEG functional
      connectivity.
AB  - We used a recently proposed graph index to investigate connectivity redundancy in
      resting state MEG recordings. Usually, brain network analyses consider indexes
      linked to the shortest paths between cerebral regions. However, important
      information might be lost about alternative trails by neglecting longer pathways.
      We measured the redundancy of the connectivity by considering the multiple paths
      at the global level (i.e., scalar redundancy), across different path lengths
      (i.e., vector redundancy), and between node pairs (i.e., matrix redundancy). We
      applied this approach to a robust frequency domain functional connectivity
      measure, the corrected imaginary part of coherence. The redundancy in the MEG
      networks, for each frequency band, was significantly (P < 0.05) higher than in
      the random graphs, thus, confirming a natural tendency of the brain to present
      multiple interaction pathways between different specialized areas. Notably, this
      difference was more evident and localized among the channels covering the
      parietooccipital areas in the alpha range of MEG oscillations (7.5-13 Hz), as
      expected in the resting state conditions. Interestingly enough, the results
      obtained with the redundancy indexes were poorly correlated with those obtained
      using shortest paths only, and more sensitive with respect to those obtained by
      considering walk-based indexes.

PMID- 23118800
TI  - A rate-distortion-based merging algorithm for compressed image segmentation.
AB  - Original images are often compressed for the communication applications. In order
      to avoid the burden of decompressing computations, it is thus desirable to
      segment images in the compressed domain directly. This paper presents a simple
      rate-distortion-based scheme to segment images in the JPEG2000 domain. It is
      based on a binary arithmetic code table used in the JPEG2000 standard, which is
      available at both encoder and decoder; thus, there is no need to transmit the
      segmentation result. Experimental results on the Berkeley image database show
      that the proposed algorithm is preferable in terms of the running time and the
      quantitative measures: probabilistic Rand index (PRI) and boundary displacement
      error (BDE).

PMID- 23118801
TI  - A fully coupled model for electromechanics of the heart.
AB  - We present a fully coupled electromechanical model of the heart. The model
      integrates cardiac electrophysiology and cardiac mechanics through excitation
      induced contraction and deformation-induced current. Numerical schemes based on
      finite element were implemented in a supercomputer. Numerical examples were
      presented using a thin cardiac tissue and a dog ventricle with realistic
      geometry. Performance of the parallel simulation scheme was studied. The model
      provides a useful tool to understand cardiovascular dynamics.

PMID- 23118802
TI  - A study of mechanical optimization strategy for cardiac resynchronization therapy
      based on an electromechanical model.
AB  - An optimal electrode position and interventricular (VV) delay in cardiac
      resynchronization therapy (CRT) improves its success. However, the precise
      quantification of cardiac dyssynchrony and magnitude of resynchronization
      achieved by biventricular (BiV) pacing therapy with mechanical optimization
      strategies based on computational models remain scant. The maximum
      circumferential uniformity ratio estimate (CURE) was used here as mechanical
      optimization index, which was automatically computed for 6 different electrode
      positions based on a three-dimensional electromechanical canine model of heart
      failure (HF) caused by complete left bundle branch block (CLBBB). VV delay timing
      was adjusted accordingly. The heart excitation propagation was simulated with a
      monodomain model. The quantification of mechanical intra- and interventricular
      asynchrony was then investigated with eight-node isoparametric element method.
      The results showed that (i) the optimal pacing location from maximal CURE of
      0.8516 was found at the left ventricle (LV) lateral wall near the equator site
      with a VV delay of 60 ms, in accordance with current clinical studies, (ii)
      compared with electrical optimization strategy of E(RMS), the LV synchronous
      contraction and the hemodynamics improved more with mechanical optimization
      strategy. Therefore, measures of mechanical dyssynchrony improve the sensitivity
      and specificity of predicting responders more. The model was subject to
      validation in future clinical studies.

PMID- 23118803
TI  - Mucus distribution model in a lung with cystic fibrosis.
AB  - Cystic fibrosis (CF) is the most common autosomal recessive disease in Caucasians
      with a reported incidence of 1 in every 3200 live births. Most strikingly, CF is
      associated with early mortality. Host in flammatory responses result in airway
      mucus plugging, airway wall edema, and eventual destruction of airway wall
      support structure. Despite aggressive treatment, the median age of survival is
      approximately 38 years. This work is the first attempt to parameterize the
      distributions of mucus in a CF lung as a function of time. By default, the model
      makes arbitrary choices at each stage of the construction process, whereby the
      simplest choice is made. The model is sophisticated enough to fit the average CF
      patients' spirometric data over time and to identify several interesting
      parameters: probability of colonization, mucus volume growth rate, and scarring
      rate. Extensions of the model appropriate for describing the dynamics of single
      patient MRI data are also discussed.

PMID- 23118804
TI  - A non-interventional study of biosimilar granulocyte colony-stimulating factor as
      prophylaxis for chemotherapy-induced neutropenia in a community oncology centre.
AB  - OBJECTIVES: Prophylaxis with granulocyte colony-stimulating factor (G-CSF)
      reduces the severity of chemotherapy-induced neutropenia. Biosimilar G-CSF is now
      approved for use, based on comparable efficacy, safety and quality with the
      originator product. METHODS: We conducted a retrospective review of patients'
      charts following the switch from originator G-CSF (Neupogen((r))) to biosimilar G
      CSF (Zarzio((r))/Filgrastim Hexal((r))) in a large community oncology practice. A
      total of 77 consecutive patients with cancer who received biosimilar G-CSF were
      reviewed, as were 25 patients who received originator G-CSF at the same centre.
      RESULTS: The median age of patients in the biosimilar G-CSF cohort was 67 years
      (range 20-83). In this cohort 48% had chemotherapy with a febrile neutropenia
      risk of >20%. Biosimilar G-CSF was given as primary prophylaxis in 52% and as
      secondary prophylaxis in 48% of patients. Age and febrile neutropenia in medical
      history or in previous chemotherapy were factors that triggered the use of G-CSF
      in patients with a febrile neutropenia risk of <20%. One patient developed
      febrile neutropenia. Neutropenia led to chemotherapy dose reductions in five
      patients (6.5%) and discontinuation in two patients (2.5%). No unexpected safety
      findings were observed. Patient characteristics were generally similar in the
      originator G-CSF cohort. Only 24% of patients had a febrile neutropenia risk >20%
      and 36% received primary prophylactic G-CSF. One patient developed febrile
      neutropenia. Neutropenia led to chemotherapy dose reductions in two patients (8%)
      and discontinuation in two patients (8%). CONCLUSIONS: Biosimilar G-CSF was
      effective and prevented dose reductions/discontinuation in the majority of
      patients. Biosimilar G-CSF was considered clinically comparable to its reference
      product.

PMID- 23118805
TI  - Unusual suspects: pulmonary opportunistic infections masquerading as tumor
      metastasis in a patient with adrenocorticotropic hormone-producing pancreatic
      neuroendocrine cancer.
AB  - Pancreatic neuroendocrine tumors (p-NETs) are a rare group of neoplasms but with
      increasing incidence. The atypical complications that arise in the setting of
      functional endocrine tumors are underreported and therefore have not received
      sufficient attention and the necessary mention in the oncology literature. The
      clinical implications of these complications pose management challenges starting
      with the difficulty in establishing diagnosis, accurate staging and optimal
      treatment of the primary process. We present the case of a middle-aged woman
      diagnosed with adrenocorticotropic hormone-producing carcinoma arising from the
      pancreas whose case was complicated by excessive uncontrolled hypercortisolism
      and reactivation of pulmonary opportunistic infections that confounded her
      management. We believe that this case illustration will be of value to practicing
      oncologists and other groups of physicians who are called upon to participate in
      the multidisciplinary treatment of these relatively rare but highly challenging
      cases.

PMID- 23118806
TI  - Antiangiogenesis therapy in the treatment of metastatic colorectal cancer.
AB  - The process of new blood vessel formation, or angiogenesis, has become an
      important target for therapeutic intervention in many cancers, including
      metastatic colorectal cancer (mCRC). The growth and metastasis of primary tumors
      is dependent upon their ability to acquire and maintain an adequate blood supply;
      however, angiogenesis in tumors is an irregular process leading to chaotic and
      hyperpermeable vessels that may result in increased intratumoral pressure and
      poor exchange of macromolecules and oxygen. It has been hypothesized that
      inhibition of angiogenesis in tumors can both impair the formation of new tumor
      blood vessels and possibly 'normalize' the existing tumor vasculature, causing a
      more efficient delivery of cytotoxic chemotherapies (CTs). Over the last decade,
      therapies that target vascular endothelial growth factor (VEGF) have become a
      component of treatment for several cancers. In particular, the combination of
      bevacizumab with established chemotherapeutic regimens for mCRC has been shown to
      improve overall and progression-free survival, as well as response rates, over CT
      alone. Agents that target various members of the VEGF family, as well as
      signaling by the VEGF receptors and their tyrosine kinase components, are
      currently under development and evaluation in clinical trials. Integration of
      these new therapies into the treatment of mCRC will ultimately increase the
      available therapeutic options for patients. Still, many challenges remain,
      including identifying and validating relevant biomarkers to guide the optimal use
      of antiangiogenesis agents.

PMID- 23118807
TI  - Older patients with breast cancer: is there bias in the treatment they receive?
AB  - Breast cancer is the most frequent malignant tumor in women worldwide and as
      breast cancer incidence increases with increasing age, over 40% of new cases are
      diagnosed in women older than 65 years of age. However, older patients are not
      treated to the same extent as younger patients and increasing age at diagnosis
      predicts deviation from guidelines for all treatment modalities. Evidence-based
      medicine in older patients is lacking as they are usually excluded from clinical
      trials often because of existing comorbidities and limited life expectancy.
      Accordingly, there is a higher competing risk of death from other causes than
      breast cancer compared with younger patients and this may have led to the false
      interpretation that prognosis of breast cancer in older patients is relatively
      good. However, every treatment modality should be evaluated during treatment
      decision making. Multimodal therapy should not be routinely withheld as data show
      that disease-specific mortality increases with age, probably due to
      undertreatment. Prognostic markers, fitness and comorbidities rather than
      chronological age should determine optimal, individualized therapy. It is
      recommended that treatment decisions should be discussed in a multidisciplinary
      setting, ideally in combination with any form of geriatric assessment, to improve
      breast cancer outcome in the older population.

PMID- 23118809
TI  - Harnessing gemcitabine metabolism: a step towards personalized medicine for
      pancreatic cancer.
AB  - Pancreatic cancer is a lethal malignancy with a 5-year survival rate of only 6%.
      Surgical resection remains the only cure, yet even after resection the 5-year
      survival is only 20% due to a high recurrence rate. Thus, a high proportion of
      patients with this disease will ultimately require systemic chemotherapy for
      advanced pancreatic cancer (APC). While the advent of personalized medicine has
      resulted in significant advances in the management of many cancer types, the
      standard of care for pancreatic cancer remains gemcitabine based, with very few
      exceptions. This article first aims to provide an overview of the benefits and
      limitations of gemcitabine alone, gemcitabine combinations, and different modes
      of administration of gemcitabine in APC. It then discusses research, suggesting
      that pharmacogenomic differences in enzymes that affect gemcitabine transport and
      metabolism can predict benefit from this drug in pancreatic cancer. Finally, the
      article outlines novel therapies and combinations that exploit these
      interindividual variations in gemcitabine metabolism to improve the efficacy of
      this drug in the management of APC.

PMID- 23118808
TI  - Overcoming docetaxel resistance in prostate cancer: a perspective review.
AB  - The treatment of metastatic castrate-resistant prostate cancer has been
      historically challenging, with few therapeutic successes. Docetaxel was the first
      cytotoxic therapy associated with a survival benefit in castrate-resistant
      prostate cancer. Toxicity is typical of other cytotoxic agents, with
      myelosuppression being the dose-limiting toxicity and neurotoxicity also a
      notable side effect for some patients. Unfortunately, a significant proportion of
      men with castrate-resistant prostate cancer will not respond to docetaxel-based
      therapy and all patients will ultimately develop resistance. Because it is an
      effective therapy, docetaxel is likely to remain an important part of the
      treatment arsenal against metastatic prostate cancer for the foreseeable future,
      despite its toxicities and limitations. Overcoming docetaxel resistance has been
      a challenge since docetaxel was first established as front-line therapy for
      metastatic castrate-resistant prostate cancer. Recent studies have shown that
      several new drugs, including cabazitaxel and abiraterone, are effective after
      docetaxel failure, dramatically changing the therapeutic landscape for these
      patients. In addition, a greater understanding of the mechanisms underlying
      docetaxel resistance has led to several new treatment approaches which hold
      promise for the future. This review will discuss recent therapeutic advances in
      metastatic castrate-resistant prostate cancer as well as ongoing clinical trials.

PMID- 23118811
TI  - Sleep complaints and daytime sleepiness among pharmaceutical students in Tripoli.
AB  - BACKGROUND: The effect of sleep difficulties has achieved a great deal of
      attention recently, with university students considered as a homogenized
      population, particularly affected by sleep habits. AIM: The objective of this
      study was to investigate whether Libyan college students experience sleep
      disturbance during their academic programmes. METHODS: A cross-sectional survey
      was conducted in the college of Pharmacy, Tripoli University, during February
      2010. A total of 201 students, including 179 females (89.05%) and 22 males
      (10.95%), were recruited from different academic levels. Data were collected
      using a structured questionnaire and included a number of life-style variables.
      Epworth Sleepiness Scale (ESS) was used for the assessment of daytime sleepiness.
      RESULTS: This study showed that the total sleep time (TST) on a weeknight was
      6.40 h and 67 students reported napping during daytime. The TST plus naps
      totalled 7.39 h. Out of eight possible dozing situations, we found that the mean
      score for ESS was 8.78. In addition, 79 students showed an ESS score of >10.
      Furthermore, our results showed that the majority of students (>92%) reported
      poor sleep satisfaction with quality and duration of sleep hours. Thinking about
      difficulty of study but not increasing education programs or tea/coffee
      consumption is associated with sleep difficulties reported. Moreover, 77.6% of
      students reported an irregular sleep-wake schedule. CONCLUSION: These findings
      indicate that students experienced excessive daytime sleepiness. The TST of
      pharmaceutical students in Libya, as in other developing countries, is less than
      those reported by Western students. Students experienced various environmental
      demands during their college years and, their quality of sleep was negatively
      affected.

PMID- 23118812
TI  - Microscopic colitis - a missed diagnosis in diarrhea-predominant irritable bowel
      syndrome.
AB  - BACKGROUND: Clinical presentation in microscopic colitis (MC) is similar in many
      cases to that of diarrhea-predominent irritable bowel syndrome (IBS-D). The
      proper differential diagnosis requires total colonoscopy with multiple biopsies
      from normal-appearing mucosa and a detailed histopathological exam. Specific
      treatment may improve symptomatology. AIM: To evaluate the prevalence of MC in
      patients with an initial diagnosis of IBS-D, to analyse demographic and clinical
      features of MC patients and to assess the efficacy of specific treatment.
      MATERIAL AND METHODS: Our retrospective study analyzed patients diagnosed with
      microscopic colitis in clinic during a three-year period. Diagnosis was
      established on histological exams of the samples obtained during colonoscopy in
      patients previously thought to have IBS-D. We evaluated clinical manifestations,
      time lapsed from their onset to definitive diagnosis, the association of MC with
      autoimmune diseases or with prior medication and the efficacy of treatment with
      budesonide or mesalazine. RESULTS: From 247 patients considered to have IBS-D, 15
      patients (6.07%) had actually MC (13 lymphocytic colitis and 2 collagenous
      colitis). MC was associated with nonsteroidal antiinflammatory drugs (3
      patients), Lansoprazole (2 patients) and autoimmune diseases (6 patients).
      Watery, non-bloody diarrhea was present in all patients with MC. Other frequent
      complaints were nocturnal diarrhea (11 patients), abdominal pain (8 patients),
      abdominal bloating and flatulence (8 patients) and slight weight loss (6
      patients). The diagnostic samples were obtained from the right colon in 6 cases
      and from rectosigmoid or transverse colon in 9 patients. Treatment was initial
      symptomatic in all patients, but there were 5 patients that required mesalazine
      and/or Budesonide, with favourable outcome. CONCLUSIONS: All the patients thought
      to have diarrhea-irritable bowel syndrome should be evaluated for microscopic
      colitis. Symptomatology is almost superimposable, but a few distinct features can
      be noticed. The proper and early diagnosis and the specific treatment may lead to
      significant clinical improvement in some difficult cases of the so-called
      "irritable bowel syndrome".

PMID- 23118813
TI  - Subtyping of BK Virus in Iranian Turkish Renal Transplant Recipients by RFLP-PCR.
AB  - INTRODUCTION: BK polyomavirus (BKV) as a member of polyomavirus family is
      prevalent in the human population. BKV persists in renal tissue after
      asymptomatic infection in childhood. The reactivation of BKV in renal transplant
      recipients sometimes can lead to BKV associated nephropathy. BKV isolates are
      classified into four serologically distinct subtypes. Present study was carried
      out to investigate the distribution pattern of BKV subtypes in Iranian Turkish
      renal transplant recipients. MATERIALS AND METHODS: Urine samples from 12 kidney
      transplant recipients infected with BKV were analyzed by RFLP-PCR technique for
      classification of subtypes. RESULTS: Our analysis showed that all samples were
      infected with BKV type I. BK virus types II, III, and IV were not detected in our
      patients. CONCLUSIONS: Based on the results of the present study, BKV subtype I
      was the most frequently detected subtype in renal transplant recipients. To our
      knowledge, the present study provides the first data regarding distribution of
      BKV subtypes in Iranian renal transplant recipients.

PMID- 23118814
TI  - The value of reference ranges for middle cerebral artery peak systolic velocity
      in the management of rhesus alloimmunized pregnancies.
AB  - OBJECTIVES: To establish reference ranges for middle cerebral artery peak
      systolic velocity (MCA PSV) and to certify their value in the management of
      Rhesus alloimmunized pregnancies. MATERIAL AND METHODS: A reference range of MCA
      PSV with gestation was constructed by studying 342 pregnancies at 25-40 weeks. A
      comparison was made between the reference ranges produced in our study and those
      already published. Fetal MCA PSV was also measured in 30 fetuses from Rhesus
      alloimmunized pregnancies at 25-39 weeks. Last MCA PSV measurement was made
      within 7 days before measurement of umbilical cord hemoglobin at delivery. MCA
      PSV and hemoglobin were expressed as multiples of median (MoM). OUTCOMES: In the
      normal pregnancies a significant increase in MCA PSV with gestation resulted. The
      reference ranges for MCA PSV in normal pregnancies were similar to those already
      in use up to 34 weeks. From 35 to 40 weeks, our values were lower. In the Rhesus
      alloimmunized pregnancies, MCA PSV was increased. We found a good correlation
      between MoM MCA PSV and MoM hemoglobin. Using a threshold of 1.29 for MoM PSV,
      the sensitivity and specificity of MCA PSV in predicting any degree of anemia (Hb
      <=0.84 MoM) were 88.46% and 98.27%. CONCLUSIONS: Our reference ranges for MCA PSV
      can perform well from 25 until 35 weeks of gestation. Based on this, measurement
      of the MCA PSV in fetuses at risk for anemia provides a reliable, non-invasive
      clinical test for the prediction of fetal anemia.

PMID- 23118815
TI  - Molecular Evaluation of the IFN gamma +874, TNF alpha -308, and IL-1Ra VNTR
      Sequences in Silicosis.
AB  - INTRODUCTION: to assess whether single nucleotide variation within regulatory
      sequences of cytokine or chemokine genes is associated with silicosis, this study
      was conducted for molecular evaluation of the IFN gamma +874, TNF alpha -308, and
      IL-1Ra VNTR sequences in the patients with the silicosis. MATERIALS AND METHODS:
      ASO-PCR technique was carried out for genotyping of IFN gamma +874 and TNF alpha 
      308, and in the case of IL-1Ra VNTR, a PCR reaction was performed. RESULTS: our
      findings implied that: 1) IFN gamma +874 T allele frequency was 0.44 in the cases
      and 0.48 in the controls; 2) IFN gamma +874 A allele frequency was 0.56 in the
      cases and 0.52 in the controls; 3) TNF alpha -308 A allele frequency was 0.34 in
      the cases and 0.29 in the controls; 4) TNF alpha -308 G allele frequency was 0.66
      in the cases and 0.71 in the controls; 5) the observed frequencies (%) of allele
      1, allele 2, allele 3 and allele 4 were 65(72.2), 18(20), 2(2.22), 5(5.56) in the
      cases respectively, and 6) 68(75.6), 17(18.9), 2(2.22), 3(3.33) in the controls
      respectively. Genotypic and allelic frequencies were not significantly different
      between cases and controls (p value > 0.05). CONCLUSIONS: it can be concluded
      that IFN gamma +874, TNF alpha -308 and IL-1Ra VNTR are not associated with
      silicosis.

PMID- 23118816
TI  - Association of pericentric inversion of chromosome 9 and infertility in romanian
      population.
AB  - BACKGROUND: One of the most common structural balanced chromosome rearrangements
      is pericentric inversion of chromosome 9; inv(9)(p11q12), which is consider to be
      the variant of normal karyotype and has been found in normal population. Although
      it seems not to correlate with abnormal phenotypes, there have been many
      controversial reports indicating that it may lead to abnormal clinical conditions
      such as infertility and recurrent abortions. The incidence is found to be about
      1% - 3% in the general population. The aim of this study was to re-evaluate the
      clinical impact of inv(9)(p11q12)/(p11q13) in infertility. MATERIALS AND METHODS:
      We investigated the karyotypes of 900 infertile couples (1800 individuals)
      admitted in our hospital for cytogenetic analysis. The control group consists of
      1116 fetuses investigated by amniocentesis. This group was considered to be a
      sample of the fertile population, as the fetus being karyotyped is the result of
      a spontaneous pregnancy. Fetal karyotyping was made according to the standard
      indications for prenatal diagnosis (abnormal maternal serum screening results).
      Chromosomes from cultured peripheral blood lymphocytes and amniotic fluid were
      analyzed using Giemsa Trypsin-Giemsa (GTG) banding. The results of the two groups
      were compared. RESULTS: 1800 infertile people were submitted for cytogenetic
      investigation. In the control group 97.73% had normal karyotype and 2.27% showed
      inversion of chromosome 9, while in the studied group 96.24% had normal karyotype
      and 3.76% showed inversion of chromosome 9. The incidence of inversion 9 in both
      male and female patients is not significantly higher comparing with normal
      population (p = 0.343, p< 0.05). CONCLUSIONS: Because a considerable proportion
      of patients with reproductive dysfunction had various cytogenetic abnormalities,
      the chromosomal analysis should be considered as a diagnostic tool in the
      evaluation of reproductive dysfunction (infertility in men due to spermatogenic
      disturbances and in recurrent spontaneous abortion in females).

PMID- 23118817
TI  - Prognostic factors in pulmonary hypertension.
AB  - BACKGROUND AND OBJECTIVES: Pulmonary hypertension is a hemodynamic and
      pathophysiological condition defined as an increase in mean pulmonary pressure
      more than or equal to 25 mm Hg. Evaluation of pulmonary hypertension severity and
      prognosis plays a central role in the management of these patients, between
      diagnosis and therapeutic decision making. The aim of our study was to identify
      the adverse prognostic factors in patients with pulmonary hypertension and their
      impact on mortality, quality of life, need for hospitalization and complications
      during hospitalization. MATERIAL AND METHODS: We performed a prospective study
      that included 553 patients diagnosed with pulmonary hypertension in the Institute
      of Cardiovascular Diseases of Iasi between 1st November 2008 and 1st July 2011.
      We analyzed a series of demographic and clinical data, echocardiographic and
      hemodynamic parameters, which correlated with mortality, WHO functional class,
      complications and need for hospitalization. OUTCOMES: We identified as main
      negative prognostic factors: WHO functional class III and IV, the pulmonary
      artery systolic pressure value, right chambers dilation, TAPSE, pericardial
      effusion, cardiac index and right atrial pressure. CONCLUSIONS: Pulmonary
      hypertension, despite the development of treatment methods, remains a serious
      disease, with progressive and inexorable evolution, but the prognosis of patients
      with pulmonary hypertension is very variable, depending on the etiology,
      functional class, clinical, echocardiographic and hemodynamic parameters.

PMID- 23118818
TI  - Toxic Metals and Essential Elements in Hair and Severity of Symptoms among
      Children with Autism.
AB  - OBJECTIVE: The objective of this study was to assess the levels of ten toxic
      metals and essential elements in hair samples of children with autism, and to
      correlate the level of these elements with the severity of autism. METHOD: The
      participants were 44 children, age 3 to 9 years, with Autistic Spectrum Disorder
      (ASD) according to Diagnostic and Statistical Manual of Mental Disorders 4th
      Edition, (DSM-IV). The severity of autistic symptomatology was measured by the
      Childhood Autism Rating Scale (CARS). Hair analysis was performed to evaluate the
      long term metal exposure and mineral level. RESULTS: By comparing hair
      concentration of autistic vs nonautistic children, elevated hair concentrations
      were noted for aluminum, arsenic, cadmium, mercury, antimony, nickel, lead, and
      vanadium. Hair levels of calcium, iron, iodine, magnesium, manganese, molybdenum,
      zinc, and selenium were considered deficient. There was a significant positive
      correlation between lead & verbal communication (p = 0.020) and general
      impression (p = 0.008). In addition, there was a significant negative correlation
      between zinc & fear and nervousness (p = 0.022). CONCLUSION: Our data supports
      the historic evidence that heavy metals play a role in the development of ASD. In
      combination with an inadequate nutritional status the toxic effect of metals
      increase along with the severity of symptoms.

PMID- 23118819
TI  - Woman health; uterus rupture, its complications and management in teaching
      hospital bannu, pakistan.
AB  - OBJECTIVES: To evaluate risk factors, management, maternal and fetal outcomes of
      ruptured uterus at Women and Children Teaching Hospital Bannu, Pakistan. STUDY
      DESIGN: The prospective observational study was designed from January 2009 to
      December 2009. A total 64 patients were found with ruptured uterus evaluated in
      Women and Children Teaching Hospital Bannu, Pakistan. The aim of the study was to
      evaluate risk factors, management, maternal and fetal outcomes. RESULTS:
      Frequency of ruptured uterus in hospital was found in 9/ 1000 deliveries, higher
      than most other studies. Amongst etiological factors the most important were
      great multiparity 27 (42.2%), injudicious use of Oxytocin 33 (51.6%), obstructed
      labour 8 (12.5%) and previous caesarean section 12 (18.8%). Of the total number
      of patients, 49 (76.6%) underwent abdominal hysterectomy (either subtotal or
      total), 3.1% of them needed bladder repair and 15.6% underwent repair of uterus.
      5 (7.8%) died either due to irreversible shock or disseminated intravascular
      coagulation, 4% of patients had incontinence of urine, 53 (82.8%) of cases
      delivered dead babies and 9 (14.1%) had severe birth asphyxia needing neonatal
      intensive care. CONCLUSION: Uterine rupture is amongst the preventable obstetric
      complication that carries severe risks both to the mother as to the baby. Health
      education of people, training and supervision of health personal may reduce
      incidence especially in remote areas.

PMID- 23118820
TI  - An in vitro Study on the Apoptosis Inducing Effects of Ultraviolet B light in
      Staphylococcus aureus.
AB  - OBJECTIVES: Staphylococcus aureus is a gram positive bacterium. In recent years,
      the incidence of Staphylococcus aureus skin and soft tissue infections has been
      steadily increased around the world. Nowaday, the phototherapy is a suitable
      alternative as a cheap and effective treatment and in some cases can be used in
      parallel with chemotherapy. That is why, in this survey, we tried to detect the
      eventual apoptosis feature in UVB-irradiated colonies of Staphylococcus aureus.
      MATERIALS AND METHODS: The bacterial sample was harvested from the microbial
      collection center of Islamic Azad University, Shahr-e-Qods branch, Microbiology
      laboratory. The colonies of Staphylococcus aureus were radiated by UVB beam and
      then, the DNA molecules belonging to control and irradiated colonies were
      extracted by DNP kit. Next after DNA extraction, the DNA molecules mixed in
      loading dye were run in 1% agarose gel electrophoresis. Following the
      electrophoresis, the UV transilluminator was used to observe the orange
      luminescent DNA bands formed in agarose gel. OUTCOMES: As it was indicated by
      experimental practices in the present investigation, no abnormalities, neither
      DNA laddering bands (apoptosis) nor smears (necrosis), were detected.
      CONCLUSIONS: According to the results showing the lack of DNA denaturation after
      UVB light exposure, a hypothesis could be advanced on the role of the Heat shock
      proteins and in particular, HSP70 which would act as an anti-apoptotic mechanism
      inhibiting the induction of apoptosis in UVB light-exposed colonies of
      Staphylococcus aureus.

PMID- 23118821
TI  - Holoprosencephaly: two case reports.
AB  - Holoprosencephaly is a rare malformation encountered in newborns. It refers to
      the absent or incomplete division of the prosencephalon.Case no. 1: a fetus was
      diagnosed by ultrasonogram at 29 weeks of gestation with alobar
      holoprosencephaly, proboscis and cyclopia. The premature infant was delivered by
      cesarean section at 32 weeks of gestation, confirming antenatal diagnosis.Case
      no. 2: a premature newborn at 29 weeks of gestation, who presented posterior pole
      of cranial cavity occupied by a translucent, asymmetrically disposed structure,
      with anatomically normal cerebellum, compressing the posterior horn of the left
      cerebral hemisphere. Lateral ventricles, had also a large communication in their
      middle with incomplete fused thalami. The diagnosis of lobar holoprosencephaly
      with arachnoid cyst was confirmed by the autopsy.

PMID- 23118822
TI  - Sonography in the management of painful shoulder in ambulatory practice - case
      report.
AB  - We present the case of an old patient with a painful shoulder, diagnosed in the
      ambulatory practice with an impingement syndrome and supraspinatus thendinopathy,
      with no response to appropriate therapeutically approach. As the MRI and
      diagnostic arthroscopy were not suitable for this patient, the sonographic
      examination changes the diagnosis to a supraspinatus complete tear with
      glenohumeral reaction and oriented the therapy, which proved to be successful.

PMID- 23118823
TI  - Parathyromatosis or recurrent multiple parathyroid adenomas? A case report.
AB  - We present a case of recurrent parathyromatosis and hyperparathyroidism installed
      14 years after parathyroidectomy that we attribute to spillage of tumor cells
      during previous parathyroidectomy. Due to lack of knowledge about the imaging
      characteristic of this entity, we aim to describe the imaging appearance of
      parathyromatosis and emphasize on the diagnostic utility of ultrasonography in
      preoperative localization and successful surgical resection of parathyromatosis.

PMID- 23118824
TI  - The Role of EGFR and HER2- Activating Mutations in Maxillary Sinus Cancer.
AB  - Head and neck cancers account for less than 5% of all cancers worldwide and for
      less than 1% of all cancer deaths in Romania. Sinonasal squamous cell carcinomas
      are malignant tumors with origin in the respiratory mucosa of the paranasal
      sinuses and the nasal cavity. Because of the proximity to different important
      structures such as the brain, the eye the relevance of a multimodal therapy is
      well known. We take into discussion not only the most recent data from novel
      agents targeting EGF receptor (EGFR), VEGF and p53 pathways for the management of
      sinonasal cancer, but also further development of multimodal approach, and the
      use of biomarkers to appreciate the progression of the disease and the prognostic
      and overall survival rate in clinical practice. EGFR alterations have been
      implicated in the pathogenesis and progression of many malignancies. EGFR
      overexpression has been studied extensively regarding its clinical use but the
      results are yet to be analyzed.

PMID- 23118825
TI  - Genetic technologies in cancer investigation - applications in aggresive lymphoid
      malignancies.

PMID- 23118827
TI  - Update in internal medicine: intensive glucose lowering does not reduce mortality
      in type 2 diabetes mellitus.

PMID- 23118826
TI  - The contribution of exercise testing in the prescription and outcome evaluation
      of exercise training in pulmonary rehabilitation.
AB  - Pulmonary rehabilitation is a comprehensive therapeutic intervention with proven
      efficacy in relieving symptoms and increasing exercise tolerance in patients with
      chronic respiratory diseases.One of the main components of a pulmonary
      rehabilitation program is lower limbs exercise training. There are several ways
      of establishing the optimal intensity of the exercise training, using the target
      heart rate, symptom scores, walking tests and laboratory exercise tests with or
      without ventilation or gas exchange measurements. Each of these methods has
      advantages and disadvantages.The gold standard in exercise capacity evaluation is
      cardiopulmonary exercise testing (CPET) which brings a high level of objectivity
      in exercise tolerance evaluation and provides information on mechanisms
      responsible for its decline; this allows a better training prescription and a
      correct evaluation of rehabilitation outcomes.

PMID- 23118828
TI  - High-concentration capsaicin patch (qutenza) - a new step in treatment of
      neuropathic pain.

PMID- 23118829
TI  - Update in endocrinology - primary hyperaldosteronism - from secondary
      hypertension towards metabolic syndrome and beyond.

PMID- 23118830
TI  - Damage-control surgery.

PMID- 23118831
TI  - Update in pancreatic cancer surgery - focus on total mesopancreas excision.

PMID- 23118832
TI  - Updates in cardiovascular surgery - hybrid procedures in acute debakey type I
      aortic dissection.

PMID- 23118843
TI  - Retraction: Livestock drugs and disease: the fatal combination behind breeding
      failure in endangered bearded vultures.

PMID- 23118833
TI  - Update in plastic surgery: facial transplantation.

PMID- 23118844
TI  - Jack-and-master trait responses to elevated CO2 and N: a comparison of native and
      introduced Phragmites australis.
AB  - Global change is predicted to promote plant invasions world-wide, reducing
      biodiversity and ecosystem function. Phenotypic plasticity may influence the
      ability of introduced plant species to invade and dominate extant communities.
      However, interpreting differences in plasticity can be confounded by phylogenetic
      differences in morphology and physiology. Here we present a novel case
      investigating the role of fitness trait values and phenotypic plasticity to
      global change factors between conspecific lineages of Phragmites australis. We
      hypothesized that due to observed differences in the competitive success of North
      American-native and Eurasian-introduced P. australis genotypes, Eurasian
      introduced P. australis would exhibit greater fitness in response to global
      change factors. Plasticity and plant performance to ambient and predicted levels
      of carbon dioxide and nitrogen pollution were investigated to understand how
      invasion pressure may change in North America under a realistic global change
      scenario. We found that the introduced Eurasian genotype expressed greater mean
      trait values in nearly every ecophysiological trait measured--aboveground and
      belowground--to elevated CO(2) and nitrogen, outperforming the native North
      American conspecific by a factor of two to three under every global change
      scenario. This response is consistent with "jack and master" phenotypic
      plasticity. We suggest that differences in plant nitrogen productivity, specific
      leaf area, belowground biomass allocation, and inherently higher relative growth
      rate are the plant traits that may enhance invasion of Eurasian Phragmites in
      North America. Given the high degree of genotypic variability within this
      species, and our limited number of genotypes, our results must be interpreted
      cautiously. Our study is the first to demonstrate the potential importance of
      jack-and-master phenotypic plasticity in plant invasions when facing imminent
      global change conditions. We suggest that jack-and-master invasive genotypes
      and/or species similar to introduced P. australis will have an increased
      ecological fitness, facilitating their invasion in both stressful and resource
      rich environments.

PMID- 23118845
TI  - A scatter-based prototype framework and multi-class extension of support vector
      machines.
AB  - We provide a novel interpretation of the dual of support vector machines (SVMs)
      in terms of scatter with respect to class prototypes and their mean. As a key
      contribution, we extend this framework to multiple classes, providing a new joint
      Scatter SVM algorithm, at the level of its binary counterpart in the number of
      optimization variables. This enables us to implement computationally efficient
      solvers based on sequential minimal and chunking optimization. As a further
      contribution, the primal problem formulation is developed in terms of regularized
      risk minimization and the hinge loss, revealing the score function to be used in
      the actual classification of test patterns. We investigate Scatter SVM properties
      related to generalization ability, computational efficiency, sparsity and
      sensitivity maps, and report promising results.

PMID- 23118846
TI  - Differential regulation of bone marrow-derived endothelial progenitor cells and
      endothelial outgrowth cells by the Notch signaling pathway.
AB  - Endothelial progenitor cells (EPCs) are heterogeneous populations of cells that
      participate in vasculogenesis and promote tissue regeneration. However the
      different roles of EPC populations in vasculogenesis and tissue regeneration, as
      well as their regulation and mechanisms remain elusive. In the present study, we
      cultured bone marrow (BM)-derived early EPCs (EEPCs) and endothelial outgrowth
      cells (EOCs), and investigated their roles in liver regeneration and their
      regulation by the Notch signaling pathway. We found that Notch signaling
      exhibited different effects on the proliferation and migration of EEPCs and EOCs.
      Our results also showed that while EEPCs failed to form vessel-like structures in
      a three dimensional sprouting model in vitro, EOCs could sprout and form
      endothelial cords, and this was regulated by the Notch signaling. We further
      showed that, by using a conditional knockout model of RBP-J (the critical
      transcription factor mediating Notch signaling), Notch signaling differentially
      regulates EEPCs and EOCs. In a partial hepatectomy (PHx) model, EEPCs Notch
      dependently benefitted liver regeneration with respect to liver function and
      hepatocyte proliferation and apoptosis. In contrast, EOCs appeared not directly
      involved in the recovery of liver function and the increase of hepatocytes. These
      data suggested that the RBP-J-mediated Notch signaling differentially regulated
      the two types of EPCs, which showed different roles in liver regeneration.

PMID- 23118847
TI  - Human initiated cascading failures in societal infrastructures.
AB  - In this paper, we conduct a systematic study of human-initiated cascading
      failures in three critical inter-dependent societal infrastructures due to
      behavioral adaptations in response to a crisis. We focus on three closely coupled
      socio-technical networks here: (i) cellular and mesh networks, (ii)
      transportation networks and (iii) mobile call networks. In crises, changes in
      individual behaviors lead to altered travel, activity and calling patterns, which
      influence the transport network and the loads on wireless networks. The
      interaction between these systems and their co-evolution poses significant
      technical challenges for representing and reasoning about these systems. In
      contrast to system dynamics models for studying these interacting
      infrastructures, we develop interaction-based models in which individuals and
      infrastructure elements are represented in detail and are placed in a common
      geographic coordinate system. Using the detailed representation, we study the
      impact of a chemical plume that has been released in a densely populated urban
      region. Authorities order evacuation of the affected area, and this leads to
      individual behavioral adaptation wherein individuals drop their scheduled
      activities and drive to home or pre-specified evacuation shelters as appropriate.
      They also revise their calling behavior to communicate and coordinate among
      family members. These two behavioral adaptations cause flash-congestion in the
      urban transport network and the wireless network. The problem is exacerbated with
      a few, already occurring, road closures. We analyze how extended periods of
      unanticipated road congestion can result in failure of infrastructures, starting
      with the servicing base stations in the congested area. A sensitivity analysis on
      the compliance rate of evacuees shows non-intuitive effect on the spatial
      distribution of people and on the loading of the base stations. For example, an
      evacuation compliance rate of 70% results in higher number of overloaded base
      stations than the evacuation compliance rate of 90%.

PMID- 23118848
TI  - Skewed production of IL-6 and TGFbeta by cultured salivary gland epithelial cells
      from patients with Sjogren's syndrome.
AB  - OBJECTIVE: To determine the cytokine production profile of cultured salivary
      gland epithelial (SGE) cells obtained from patients with Sjogren's syndrome (SS).
      METHODS: SGE cells obtained from 9 SS patients and 6 normal controls were
      cultured in the presence of exogenous IFNgamma. Cell proliferation and apoptosis
      in response to IFNgamma were determined by WST1 assay and by FACS analysis. The
      concentrations of IL-6 and TGFbeta secreted into culture supernatants were
      analyzed by ELISA. RESULTS: IFNgamma did not significantly affect the
      proliferation or apoptosis of SGE cells. However, IL-6 concentrations were
      higher, and TGFbeta concentrations were lower, in culture supernatants of SGE
      cells from SS patients than from normal controls. CONCLUSION: Cytokine production
      by SGE cells from SS patients showed a skewed balance compared with normal
      controls, with increased IL-6 and decreased TGFbeta secretion. This imbalance may
      be critical in the regulation of Treg/Th17 cells and may foster a pathogenic
      milieu that may be causative and predictive in SS.

PMID- 23118849
TI  - Multi-gene analysis reveals a lack of genetic divergence between Calanus
      agulhensis and C. sinicus (Copepoda; Calanoida).
AB  - The discrimination and taxonomic identification of marine species continues to
      pose a challenge despite the growing number of diagnostic metrics and approaches.
      This study examined the genetic relationship between two sibling species of the
      genus Calanus (Crustacea; Copepoda; Calanidae), C. agulhensis and C. sinicus,
      using a multi-gene analysis. DNA sequences were determined for portions of the
      mitochondrial cytochrome c oxidase I (mtCOI); nuclear citrate synthase (CS), and
      large subunit (28S) rRNA genes for specimens collected from the Sea of Japan and
      North East (NE) Pacific Ocean for C. sinicus and from the Benguela Current and
      Agulhas Bank, off South Africa, for C. agulhensis. For mtCOI, C. sinicus and C.
      agulhensis showed similar levels of haplotype diversity (H(d) = 0.695 and 0.660,
      respectively) and nucleotide diversity (pi = 0.003 and 0.002, respectively).
      Pairwise F(ST) distances for mtCOI were significant only between C. agulhensis
      collected from the Agulhas and two C. sinicus populations: the Sea of Japan
      (F(ST) = 0.152, p<0.01) and NE Pacific (F(ST) = 0.228, p<0.005). Between the
      species, F(ST) distances were low for both mtCOI (F(ST) = 0.083, p = 0.003) and
      CS (F(ST) = 0.050, p = 0.021). Large subunit (28S) rRNA showed no variation
      between the species. Our results provide evidence of the lack of genetic
      distinction of C. sinicus and C. agulhensis, raise questions of whether C.
      agulhensis warrants status as a distinct species, and indicate the clear need for
      more intensive and extensive ecological and genetic analysis.

PMID- 23118850
TI  - Emotional and social mind training: a randomised controlled trial of a new group
      based treatment for bulimia nervosa.
AB  - OBJECTIVE: There is a need to improve treatment for individuals with bulimic
      disorders. It was hypothesised that a focus in treatment on broader emotional and
      social/interpersonal issues underlying eating disorders would increase treatment
      efficacy. This study tested a novel treatment based on the above hypothesis, an
      Emotional and Social Mind Training Group (ESM), against a Cognitive Behavioural
      Therapy Group (CBT) treatment. METHOD: 74 participants were randomised to either
      ESM or CBT Group treatment programmes. All participants were offered 13 group and
      4 individual sessions. The primary outcome measure was the Eating Disorder
      Examination (EDE) Global score. Assessments were carried out at baseline, end of
      treatment (four months) and follow-up (six months). RESULTS: There were no
      differences in outcome between the two treatments. No moderators of treatment
      outcome were identified. Adherence rates were higher for participants in the ESM
      group. DISCUSSION: This suggests that ESM may be a viable alternative to CBT for
      some individuals. Further research will be required to identify and
      preferentially allocate suitable individuals accordingly. TRIAL REGISTRATION:
      ISRCTN61115988.

PMID- 23118851
TI  - Docosahexaenoic acid signaling modulates cell survival in experimental ischemic
      stroke penumbra and initiates long-term repair in young and aged rats.
AB  - BACKGROUND: Docosahexaenoic acid, a major omega-3 essential fatty acid family
      member, improves behavioral deficit and reduces infarct volume and edema after
      experimental focal cerebral ischemia. We hypothesize that DHA elicits
      neuroprotection by inducing AKT/p70S6K phosphorylation, which in turn leads to
      cell survival and protects against ischemic stroke in young and aged rats.
      METHODS AND RESULTS: Rats underwent 2 h of middle cerebral artery occlusion
      (MCAo). DHA, neuroprotectin D1 (NPD1) or vehicle (saline) was administered 3 h
      after onset of stroke. Neurological function was evaluated on days 1, 2, 3, and
      7. DHA treatment improved functional recovery and reduced cortical, subcortical
      and total infarct volumes 7 days after stroke. DHA also reduced microglia
      infiltration and increased the number of astrocytes and neurons when compared to
      vehicle on days 1 and 7. Increases in p473 AKT and p308 AKT
      phosphorylation/activation were observed in animals treated with DHA 4 h after
      MCAo. Activation of other members of the AKT signaling pathway were also observed
      in DHA treated animals including increases in pS6 at 4 h and pGSK at 24 h. DHA or
      NPD1 remarkably reduced total and cortical infarct in aged rats. Moreover, we
      show that in young and aged rats DHA treatment after MCAo potentiates NPD1
      biosynthesis. The phosphorylation of p308 AKT or pGSK was not different between
      groups in aged rats. However, pS6 expression was increased with DHA or NPD1
      treatment when compared to vehicle. CONCLUSIONS: We suggest that DHA induces cell
      survival, modulates the neuroinflammatory response and triggers long term
      restoration of synaptic circuits. Both DHA and NPD1 elicited remarkable
      protection in aged animals. Accordingly, activation of DHA signaling might
      provide benefits in the management of ischemic stroke both acutely as well as
      long term to limit ensuing disabilities.

PMID- 23118852
TI  - Comparison of peripheral and central schizophrenia biomarker profiles.
AB  - We have recently shown that a molecular biomarker signature comprised of
      inflammatory, hormonal and growth factors occurs in the blood serum from first
      onset schizophrenia patients. Here, we use the same platform to investigate post
      mortem brain tissue (Brodmann area 10) from schizophrenia patients who were
      mainly chronically ill and drug treated. Twenty-one analytes are differentially
      expressed in post-mortem brain tissue. Comparison with our previous mRNA
      profiling studies of the same patient samples in another frontal cortical area
      showed that 9 of these molecules were also altered at the transcriptional level.
      Furthermore, 9 of the molecules were also altered in serum from living first
      onset schizophrenia patients compared to controls. We propose a model in which
      the brain and periphery are coordinated through hormones and other regulatory
      molecules released into the blood via the diffuse neuroendocrine system. These
      findings provide further evidence for the systemic nature of schizophrenia and
      give added validity to the concept that schizophrenia can be investigated through
      studies of blood-based biomarkers.

PMID- 23118853
TI  - Risk of maltreatment-related injury: a cross-sectional study of children under
      five years old admitted to hospital with a head or neck injury or fracture.
AB  - OBJECTIVES: To determine the predictive value and sensitivity of demographic
      features and injuries (indicators) for maltreatment-related codes in hospital
      discharge records of children admitted with a head or neck injury or fracture.
      METHODS:  STUDY DESIGN: Population-based, cross sectional study. SETTING: NHS
      hospitals in England. SUBJECTS: Children under five years old admitted acutely to
      hospital with head or neck injury or fracture. DATA SOURCE: Hospital Episodes
      Statistics, 1997 to 2009. MAIN OUTCOME MEASURE: Maltreatment-related injury
      admissions, defined by ICD10 codes, were used to calculate for each indicator
      (demographic feature and/or type of injury): i) the predictive value (proportion
      of injury admissions that were maltreatment-related); ii) sensitivity (proportion
      of all maltreatment-related injury admissions with the indicator). RESULTS: Of
      260,294 childhood admissions for fracture or head or neck injury, 3.2% (8,337)
      were maltreatment-related. With increasing age of the child, the predictive value
      for maltreatment-related injury declined but sensitivity increased. Half of the
      maltreatment-related admissions occurred in children older than one year, and 63%
      occurred in children with head injuries without fractures or intracranial injury.
      CONCLUSIONS: Highly predictive injuries accounted for very few maltreatment
      related admissions. Protocols that focus on high-risk injuries may miss the
      majority of maltreated children.

PMID- 23118854
TI  - A complex set of sex pheromones identified in the cuttlefish Sepia officinalis.
AB  - BACKGROUND: The cephalopod mollusk Sepia officinalis can be considered as a
      relevant model for studying reproduction strategies associated to seasonal
      migrations. Using transcriptomic and peptidomic approaches, we aim to identify
      peptide sex pheromones that are thought to induce the aggregation of mature
      cuttlefish in their egg-laying areas. RESULTS: To facilitate the identification
      of sex pheromones, 576 5'-expressed sequence tags (ESTs) were sequenced from a
      single cDNA library generated from accessory sex glands of female cuttlefish. Our
      analysis yielded 223 unique sequences composed of 186 singletons and 37 contigs.
      Three major redundant ESTs called SPalpha, SPalpha' and SPbeta were identified as
      good candidates for putative sex pheromone transcripts and are part of the 87
      unique sequences classified as unknown. The alignment of translated SPalpha and
      SPalpha' revealed a high level of conservation, with 98.4% identity. Translation
      led to a 248-amino acid precursor containing six peptides with multiple putative
      disulfide bonds. The alignment of SPalpha-alpha' with SPbeta revealed a partial
      structural conservation, with 37.3% identity. Translation of SPbeta led to a 252
      amino acid precursor containing five peptides. The occurrence of a signal peptide
      on SPalpha, SPalpha' and SPbeta showed that the peptides were secreted. RT-PCR
      and mass spectrometry analyses revealed a co-localization of transcripts and
      expression products in the oviduct gland. Preliminary in vitro experiments
      performed on gills and penises revealed target organs involved in mating and
      ventilation. CONCLUSIONS: The analysis of the accessory sex gland transcriptome
      of Sepia officinalis led to the identification of peptidic sex pheromones.
      Although preliminary functional tests suggested the involvement of the alpha3 and
      beta2 peptides in ventilation and mating stimulation, further functional
      investigations will make it possible to identify the complete set of biological
      activities expected from waterborne pheromones.

PMID- 23118855
TI  - A genetic variant in pre-miR-27a is associated with a reduced renal cell cancer
      risk in a Chinese population.
AB  - BACKGROUND: MicroRNAs (miRNAs) are a class of small non-coding RNAs to regulate
      cell differentiation, proliferation, development, and apoptosis. The single
      nucleotide polymorphism (SNP) rs895819 is located at the terminal loop of pre-miR
      27a. Here, we aimed to investigate whether SNP rs895819 was associated with the
      development of renal cell cancer (RCC) in a Chinese population. METHODS: In this
      case-control study, we recruited 594 RCC patients and 600 cancer-free controls
      with frequency matched by age and sex. We genotyped this polymorphism using the
      TaqMan assay and assessed the effect of this polymorphism on RCC survival.
      Logistic regression model was used to assess the genetic effects on the
      development of RCC and interactions between rs895819 polymorphism and risk
      factors. RESULTS: Compared with AA homozygote, individuals carrying AG/GG
      genotypes had a statistically significant reduced susceptibility to RCC (adjusted
      OR = 0.71, 95% CI = 0.56-0.90). Furthermore, AG/GG genotypes were associated with
      reduced RCC susceptibility in localized clinical stage (adjusted OR = 0.71, 95%
      CI = 0.55-0.91), and similar effects were observed in well differentiated and
      poorly differentiated RCC (adjusted OR = 0.71, 95% CI = 0.55-0.93 for well
      differentiated, adjusted OR = 0.51, 95% CI = 0.28-0.93 for poorly
      differentiated). We also observed that rs895819 had multiplicative interactions
      with age and hypertension. However, the polymorphism did not influence the
      survival of RCC. CONCLUSION: Our results suggest that the pre-miR-27a rs895819
      polymorphism can predict RCC risk in a Chinese population. Larger population
      based prospective studies should be used to validate our findings.

PMID- 23118856
TI  - Regulatory T-cells and associated pathways in metastatic renal cell carcinoma
      (mRCC) patients undergoing DC-vaccination and cytokine-therapy.
AB  - PURPOSE: To evaluate CD4(+)CD25(+)FOXP3(+) T regulatory cells (T(REG)) and
      associated immune-regulatory pathways in peripheral blood lymphocytes (PBL) of
      metastatic renal cell carcinoma (mRCC) patients and healthy volunteers. We
      subsequently investigated the effects of immunotherapy on circulating T(REG)
      combining an extensive phenotype examination, DNA methylation analysis and global
      transcriptome analysis. DESIGN: Eighteen patients with mRCC and twelve volunteers
      (controls) were available for analysis. T(REG) phenotype was examined using flow
      cytometry (FCM). T(REG) were also quantified by analyzing the epigenetic status
      of the FOXP3 locus using methylation specific PCR. As a third approach, RNA of
      the PBL was hybridized to Affymetrix GeneChip Human Gene 1.0 ST Arrays and the
      gene signatures were explored using pathway analysis. RESULTS: We observed higher
      numbers of T(REG) in pre-treatment PBL of mRCC patients compared to controls. A
      significant increase in T(REG) was detected in all mRCC patients after the two
      cycles of immunotherapy. The expansion of T(REG) was significantly higher in non
      responders than in responding patients. Methylation specific PCR confirmed the
      FCM data and circumvented the variability and subjectivity of the FCM method.
      Gene Set Enrichment Analysis (GSEA) of the microarray data showed significant
      enrichment of FOXP3 target genes, CTLA-4 and TGF-beta associated pathways in the
      patient cohort. CONCLUSION: Immune monitoring of the peripheral blood and tumor
      tissue is important for a wide range of diseases and treatment strategies.
      Adoption of methodology for quantifying T(REG) with the least variability and
      subjectivity will enhance the ability to compare and interpret findings across
      studies.

PMID- 23118857
TI  - A fish-specific transposable element shapes the repertoire of p53 target genes in
      zebrafish.
AB  - Transposable elements, as major components of most eukaryotic organisms' genomes,
      define their structural organization and plasticity. They supply host genomes
      with functional elements, for example, binding sites of the pleiotropic master
      transcription factor p53 were identified in LINE1, Alu and LTR repeats in the
      human genome. Similarly, in this report we reveal the role of zebrafish (Danio
      rerio) EnSpmN6_DR non-autonomous DNA transposon in shaping the repertoire of the
      p53 target genes. The multiple copies of EnSpmN6_DR and their embedded p53
      responsive elements drive in several instances p53-dependent transcriptional
      modulation of the adjacent gene, whose human orthologs were frequently previously
      annotated as p53 targets. These transposons define predominantly a set of target
      genes whose human orthologs contribute to neuronal morphogenesis, axonogenesis,
      synaptic transmission and the regulation of programmed cell death. Consistent
      with these biological functions the orthologs of the EnSpmN6_DR-colonized loci
      are enriched for genes expressed in the amygdala, the hippocampus and the brain
      cortex. Our data pinpoint a remarkable example of convergent evolution: the
      exaptation of lineage-specific transposons to shape p53-regulated neuronal
      morphogenesis-related pathways in both a hominid and a teleost fish.

PMID- 23118858
TI  - Evaluation of IL-28B polymorphisms and serum IP-10 in hepatitis C infected
      chimpanzees.
AB  - In humans, clearance of hepatitis C virus (HCV) infection is associated with
      genetic variation near the IL-28B gene and the induction of interferon-stimulated
      genes, like IP-10. Also in chimpanzees spontaneous clearance of HCV is observed.
      To study whether similar correlations exist in these animals, a direct comparison
      of IP-10 and IL-28B polymorphism between chimpanzees and patients was performed.
      All chimpanzees studied were monomorphic for the human IL-28B SNPs which are
      associated with spontaneous and treatment induced HCV clearance in humans. As a
      result, these particular SNPs cannot be used for clinical association studies in
      chimpanzees. Although these human SNPs were absent in chimpanzees, gene variation
      in this region was present however, no correlation was observed between different
      SNP-genotypes and HCV outcome. Strikingly, IP-10 levels in chimpanzees correlated
      with HCV-RNA load and gammaGT, while such correlations were not observed in
      humans. The correlation between IP-10, gammaGT and virus load in chimpanzees was
      not found in patients and may be due to the lack of lifestyle-related confounding
      factors in chimpanzees. Direct comparison of IP-10 and IL-28B polymorphism
      between chimpanzees and patients in relation to HCV infection, illustrates that
      the IFN-pathways are important during HCV infection in both species. The Genbank
      EMBL accession numbers assigned to chimpanzees specific sequences near the IL-28B
      gene are HE599784 and HE599785.

PMID- 23118860
TI  - Amino acid substitutions of MagA in Klebsiella pneumoniae affect the biosynthesis
      of the capsular polysaccharide.
AB  - Mucoviscosity-associated gene A (magA) of Klebsiella pneumoniae contributes to K1
      capsular polysaccharide (CPS) biosynthesis. Based on sequence homology and gene
      alignment, the magA gene has been predicted to encode a Wzy-type CPS polymerase.
      Sequence alignment with the Wzy_C and RfaL protein families (which catalyze CPS
      or lipopolysaccharide (LPS) biosynthesis) and topological analysis has suggested
      that eight highly conserved residues, including G308, G310, G334, G337, R290,
      P305, H323, and N324, were located in a hypothetical loop region. Therefore, we
      used site-directed mutagenesis to study the role of these residues in CPS
      production, and to observe the consequent phenotypes such as mucoviscosity, serum
      and phagocytosis resistance, and virulence (as assessed in mice) in pyogenic
      liver abscess strain NTUH-K2044. Alanine substitutions at R290 or H323 abolished
      all of these properties. The G308A mutant was severely impaired for these
      functions. The G334A mutant remained mucoid with decreased CPS production, but
      its virulence was significantly reduced in vivo. No phenotypic change was
      observed for strains harboring magA G310A, G337A, P305A, or N324A mutations.
      Therefore, R290, G308, H323, and G334 are functionally important residues of the
      MagA (Wzy) protein of K. pneumoniae NTUH-K2044, capsular type K1. These amino
      acids are also likely to be important for the function of Wzy in other capsular
      types in K. pneumoniae and other species bearing Wzy_C family proteins.

PMID- 23118859
TI  - Dynamics of membrane potential variation and gene expression induced by
      Spodoptera littoralis, Myzus persicae, and Pseudomonas syringae in Arabidopsis.
AB  - BACKGROUND: Biotic stress induced by various herbivores and pathogens invokes
      plant responses involving different defense mechanisms. However, we do not know
      whether different biotic stresses share a common response or which signaling
      pathways are involved in responses to different biotic stresses. We investigated
      the common and specific responses of Arabidopsis thaliana to three biotic stress
      agents: Spodoptera littoralis, Myzus persicae, and the pathogen Pseudomonas
      syringae. METHODOLOGY/PRINCIPAL FINDINGS: We used electrophysiology to determine
      the plasma membrane potential (V(m)) and we performed a gene microarray
      transcriptome analysis on Arabidopsis upon either herbivory or bacterial
      infection. V(m) depolarization was induced by insect attack; however, the
      response was much more rapid to S. littoralis (30 min -2 h) than to M. persicae
      (4-6 h). M. persicae differentially regulated almost 10-fold more genes than by
      S. littoralis with an opposite regulation. M. persicae modulated genes involved
      in flavonoid, fatty acid, hormone, drug transport and chitin metabolism. S.
      littoralis regulated responses to heat, transcription and ion transport. The
      latest Vm depolarization (16 h) was found for P. syringae. The pathogen regulated
      responses to salicylate, jasmonate and to microorganisms. Despite this late
      response, the number of genes differentially regulated by P. syringae was closer
      to those regulated by S. littoralis than by M. persicae.
      CONCLUSIONS/SIGNIFICANCE: Arabidopsis plasma membranes respond with a V(m)
      depolarization at times depending on the nature of biotic attack which allow
      setting a time point for comparative genome-wide analysis. A clear relationship
      between V(m) depolarization and gene expression was found. At V(m) depolarization
      timing, M. persicae regulates a wider array of Arabidopsis genes with a clear and
      distinct regulation than S. littoralis. An almost completely opposite regulation
      was observed between the aphid and the pathogen, with the former suppressing and
      the latter activating Arabidopsis defense responses.

PMID- 23118861
TI  - A new rhynchocephalian from the late jurassic of Germany with a dentition that is
      unique amongst tetrapods.
AB  - BACKGROUND: Rhynchocephalians, the sister group of squamates (lizards and
      snakes), are only represented by the single genus Sphenodon today. This taxon is
      often considered to represent a very conservative lineage. However,
      rhynchocephalians were common during the late Triassic to latest Jurassic
      periods, but rapidly declined afterwards, which is generally attributed to their
      supposedly adaptive inferiority to squamates and/or Mesozoic mammals, which
      radiated at that time. New finds of Mesozoic rhynchocephalians can thus provide
      important new information on the evolutionary history of the group. PRINCIPLE
      FINDINGS: A new fossil relative of Sphenodon from the latest Jurassic of southern
      Germany, Oenosaurus muehlheimensis gen. et sp. nov., presents a dentition that is
      unique amongst tetrapods. The dentition of this taxon consists of massive,
      continuously growing tooth plates, probably indicating a crushing dentition, thus
      representing a previously unknown trophic adaptation in rhynchocephalians.
      CONCLUSIONS/SIGNIFICANCE: The evolution of the extraordinary dentition of
      Oenosaurus from the already highly specialized Zahnanlage generally present in
      derived rhynchocephalians demonstrates an unexpected evolutionary plasticity of
      these animals. Together with other lines of evidence, this seriously casts doubts
      on the assumption that rhynchocephalians are a conservative and adaptively
      inferior lineage. Furthermore, the new taxon underlines the high morphological
      and ecological diversity of rhynchocephalians in the latest Jurassic of Europe,
      just before the decline of this lineage on this continent. Thus, selection
      pressure by radiating squamates or Mesozoic mammals alone might not be sufficient
      to explain the demise of the clade in the Late Mesozoic, and climate change in
      the course of the fragmentation of the supercontinent of Pangaea might have
      played a major role.

PMID- 23118862
TI  - Matrix stiffness regulates endothelial cell proliferation through septin 9.
AB  - Endothelial proliferation, which is an important process in vascular homeostasis,
      can be regulated by the extracellular microenvironment. In this study we
      demonstrated that proliferation of endothelial cells (ECs) was enhanced on
      hydrogels with high stiffness (HSG, 21.5 kPa) in comparison to those with low
      stiffness (LSG, 1.72 kPa). ECs on HSG showed markedly prominent stress fibers and
      a higher RhoA activity than ECs on LSG. Blockade of RhoA attenuated stress fiber
      formation and proliferation of ECs on HSG, but had little effect on ECs on LSG;
      enhancement of RhoA had opposite effects. The phosphorylations of Src and Vav2,
      which are positive RhoA upstream effectors, were higher in ECs on HSG. The
      inhibition of Src/Vav2 attenuated the HSG-mediated RhoA activation and EC
      proliferation but exhibited nominal effects on ECs on LSG. Septin 9 (SEPT9), the
      negative upstream effector for RhoA, was significantly higher in ECs on LSG. The
      inhibition of SEPT9 increased RhoA activation, Src/Vav2 phosphorylations, and EC
      proliferation on LSG, but showed minor effects on ECs on HSG. We further
      demonstrated that the inactivation of integrin alpha(v)beta(3) caused an increase
      of SEPT9 expression in ECs on HSG to attenuate Src/Vav2 phosphorylations and
      inhibit RhoA-dependent EC proliferation. These results demonstrate that the
      SEPT9/Src/Vav2/RhoA pathway constitutes an important molecular mechanism for the
      mechanical regulation of EC proliferation.

PMID- 23118863
TI  - Non-gaussian distributions affect identification of expression patterns,
      functional annotation, and prospective classification in human cancer genomes.
AB  - INTRODUCTION: Gene expression data is often assumed to be normally-distributed,
      but this assumption has not been tested rigorously. We investigate the
      distribution of expression data in human cancer genomes and study the
      implications of deviations from the normal distribution for translational
      molecular oncology research. METHODS: We conducted a central moments analysis of
      five cancer genomes and performed empiric distribution fitting to examine the
      true distribution of expression data both on the complete-experiment and on the
      individual-gene levels. We used a variety of parametric and nonparametric methods
      to test the effects of deviations from normality on gene calling, functional
      annotation, and prospective molecular classification using a sixth cancer genome.
      RESULTS: Central moments analyses reveal statistically-significant deviations
      from normality in all of the analyzed cancer genomes. We observe as much as 37%
      variability in gene calling, 39% variability in functional annotation, and 30%
      variability in prospective, molecular tumor subclassification associated with
      this effect. CONCLUSIONS: Cancer gene expression profiles are not normally
      distributed, either on the complete-experiment or on the individual-gene level.
      Instead, they exhibit complex, heavy-tailed distributions characterized by
      statistically-significant skewness and kurtosis. The non-Gaussian distribution of
      this data affects identification of differentially-expressed genes, functional
      annotation, and prospective molecular classification. These effects may be
      reduced in some circumstances, although not completely eliminated, by using
      nonparametric analytics. This analysis highlights two unreliable assumptions of
      translational cancer gene expression analysis: that "small" departures from
      normality in the expression data distributions are analytically-insignificant and
      that "robust" gene-calling algorithms can fully compensate for these effects.

PMID- 23118864
TI  - GFP's mechanical intermediate states.
AB  - Green fluorescent protein (GFP) mutants have become the most widely used
      fluorescence markers in the life sciences, and although they are becoming
      increasingly popular as mechanical force or strain probes, there is little direct
      information on how their fluorescence changes when mechanically stretched. Here
      we derive high-resolution structural models of the mechanical intermediate states
      of stretched GFP using steered molecular dynamics (SMD) simulations. These
      structures were used to produce mutants of EGFP and EYFP that mimic GFP's
      different mechanical intermediates. A spectroscopic analysis revealed that a
      population of EGFP molecules with a missing N-terminal alpha-helix was
      significantly dimmed, while the fluorescence lifetime characteristic of the
      anionic chromophore state remained unaffected. This suggests a mechanism how N
      terminal deletions can switch the protonation state of the chromophore, and how
      the fluorescence of GFP molecules in response to mechanical disturbance might be
      turned off.

PMID- 23118865
TI  - The inheritance pattern of 24 nt siRNA clusters in arabidopsis hybrids is
      influenced by proximity to transposable elements.
AB  - Hybrids often display increased size and growth, and thus are widely cultivated
      in agriculture and horticulture. Recent discoveries demonstrating the important
      regulatory roles of small RNAs have greatly improved our understanding of many
      basic biological questions, and could illuminate the molecular basis for the
      enhanced growth and size of hybrid plants. We profiled small RNAs by deep
      sequencing to characterize the inheritance patterns of small RNA levels in
      reciprocal hybrids of two Arabidopsis thaliana accessions, Columbia and Landsberg
      erecta. We find 24-nt siRNAs predominate among those small RNAs that are
      differentially expressed between the parents. Following hybridization, the
      transposable element (TE)-derived siRNAs are often inherited in an additive
      manner, whereas siRNAs associated with protein-coding genes are often down
      regulated in hybrids to the levels observed for the parent with lower relative
      siRNA levels. Among the protein-coding genes that exhibit this pattern, genes
      that function in pathogen defense, abiotic stress tolerance, and secondary
      metabolism are significantly enriched. Small RNA clusters from protein-coding
      genes where a TE is present within one kilobase show a different predominant
      inheritance pattern (additive) from those that do not (low-parent dominance).
      Thus, down-regulation in the form of low-parent dominance is likely the default
      pattern of inheritance for genic siRNA, and a different inheritance mechanism for
      TE siRNA is suggested.

PMID- 23118866
TI  - Distinct distribution of ectopically expressed histone variants H2A.Bbd and
      MacroH2A in open and closed chromatin domains.
AB  - BACKGROUND: It becomes increasingly evident that nuclesomes are far from being
      identical to each other. This nucleosome diversity is due partially to the
      existence of histone variants encoded by separate genes. Among the known histone
      variants the less characterized are H2A.Bbd and different forms of macroH2A. This
      is especially true in the case of H2A.Bbd as there are still no commercially
      available antibodies specific to H2A.Bbd that can be used for chromatin
      immunoprecipitation (ChIP). METHODS: We have generated HeLa S3 cell lines stably
      expressing epitope-tagged versions of macroH2A1.1, H2A.Bbd or canonical H2A and
      analyzed genomic distribution of the tagged histones using ChIP-on-chip
      technique. RESULTS: The presence of histone H2A variants macroH2A1.1 and H2A.Bbd
      has been analyzed in the chromatin of several segments of human chromosomes 11,
      16 and X that have been chosen for their different gene densities and chromatin
      status. Chromatin immunoprecipitation (ChIP) followed by hybridization with
      custom NimbleGene genomic microarrays demonstrated that in open chromatin domains
      containing tissue-specific along with housekeeping genes, the H2A.Bbd variant was
      preferentially associated with the body of a subset of transcribed genes. The
      macroH2A1.1 variant was virtually absent from some genes and underrepresented in
      others. In contrast, in closed chromatin domains which contain only tissue
      specific genes inactive in HeLa S3 cells, both macroH2A1.1 and H2A.Bbd histone
      variants were present and often colocalized. CONCLUSIONS: Genomic distribution of
      macro H2A and H2A.Bbd does not follow any simple rule and is drastically
      different in open and closed genomic domains.

PMID- 23118867
TI  - Mechanisms of xenogeneic baboon platelet aggregation and phagocytosis by porcine
      liver sinusoidal endothelial cells.
AB  - BACKGROUND: Baboons receiving xenogeneic livers from wild type and transgenic
      pigs survive less than 10 days. One of the major issues is the early development
      of profound thrombocytopenia that results in fatal hemorrhage. Histological
      examination of xenotransplanted livers has shown baboon platelet activation,
      phagocytosis and sequestration within the sinusoids. In order to study the
      mechanisms of platelet consumption in liver xenotransplantation, we have
      developed an in vitro system to examine the interaction between pig endothelial
      cells with baboon platelets and to thereby identify molecular mechanisms and
      therapies. METHODS: Fresh pig hepatocytes, liver sinusoidal and aortic
      endothelial cells were isolated by collagenase digestion of livers and processing
      of aortae from GTKO and Gal+ MGH-miniature swine. These primary cell cultures
      were then tested for the differential ability to induce baboon or pig platelet
      aggregation. Phagocytosis was evaluated by direct observation of CFSE labeled
      platelets, which are incubated with endothelial cells under confocal light
      microscopy. Aurintricarboxylic acid (GpIb antagonist blocking interactions with
      von Willebrand factor/vWF), eptifibatide (Gp IIb/IIIa antagonist), and anti-Mac-1
      Ab (anti-alpha(M)beta(2) integrin Ab) were tested for the ability to inhibit
      phagocytosis. RESULTS: None of the pig cells induced aggregation or phagocytosis
      of porcine platelets. However, pig hepatocytes, liver sinusoidal and aortic
      endothelial cells (GTKO and Gal+) all induced moderate aggregation of baboon
      platelets. Importantly, pig liver sinusoidal endothelial cells efficiently
      phagocytosed baboon platelets, while pig aortic endothelial cells and hepatocytes
      had minimal effects on platelet numbers. Anti-MAC-1 Ab, aurintricarboxylic acid
      or eptifibatide, significantly decreased baboon platelet phagocytosis by pig
      liver endothelial cells (P<0.01). CONCLUSIONS: Although pig hepatocytes and
      aortic endothelial cells directly caused aggregation of baboon platelets, only
      pig liver endothelial cells efficiently phagocytosed baboon platelets. Blocking
      vWF and integrin adhesion pathways prevented both aggregation and phagocytosis.

PMID- 23118868
TI  - Emotional speech processing at the intersection of prosody and semantics.
AB  - The ability to accurately perceive emotions is crucial for effective social
      interaction. Many questions remain regarding how different sources of emotional
      cues in speech (e.g., prosody, semantic information) are processed during
      emotional communication. Using a cross-modal emotional priming paradigm (Facial
      affect decision task), we compared the relative contributions of processing
      utterances with single-channel (prosody-only) versus multi-channel (prosody and
      semantic) cues on the perception of happy, sad, and angry emotional expressions.
      Our data show that emotional speech cues produce robust congruency effects on
      decisions about an emotionally related face target, although no processing
      advantage occurred when prime stimuli contained multi-channel as opposed to
      single-channel speech cues. Our data suggest that utterances with prosodic cues
      alone and utterances with combined prosody and semantic cues both activate
      knowledge that leads to emotional congruency (priming) effects, but that the
      convergence of these two information sources does not always heighten access to
      this knowledge during emotional speech processing.

PMID- 23118869
TI  - Lower healthcare costs associated with the use of a single-pill ARV regimen in
      the UK, 2004-2008.
AB  - AIM: Investigate the cost and effects of a single-pill versus two- or three pill
      first-line antiretroviral combinations in reducing viral load, increasing CD4
      counts, and first-line failure rate associated with respective regimens at 6 and
      12 months. METHODS: Patients on first-line TDF+3TC+EFV, TDF+FTC+EFV,
      Truvada(r)+EFV or Atripla(r) between 1996-2008 were identified and viral load and
      CD4 counts measured at baseline, six and twelve months respectively. Factors that
      independently predicted treatment failure at six and twelve months were derived
      using multivariate Cox's proportional hazard regression analyses. Use and cost of
      hospital services were calculated at six and twelve months respectively. RESULTS:
      All regimens reduced viral load to below the limit of detection and CD4 counts
      increased to similar levels at six and twelve months for all treatment regimens.
      No statistically significant differences were observed for rate of treatment
      failure at six and twelve months. People on Atripla(r) generated lower healthcare
      costs for non-AIDS patients at L5,340 (L5,254 to L5,426) per patient-semester and
      L9,821 (L9,719 to L9,924) per patient-year that was L1,344 (95%CI L1,222 to
      L1,465) less per patient-semester and L1,954 (95%CI L1,801 to L2,107) less per
      patient-year compared with Truvada(r)+EFV; healthcare costs for AIDS patients
      were similar across all regimens. CONCLUSION: The single pill regimen is as
      effective as the two- and three-pill regimens of the same drugs, but if started
      as first-line induction therapy there would be a 20% savings on healthcare costs
      at six and 17% of costs at twelve months compared with Truvada(r)+EFV, that
      generated the next lowest costs.

PMID- 23118870
TI  - A role for transcription factor GTF2IRD2 in executive function in Williams-Beuren
      syndrome.
AB  - Executive functions are amongst the most heritable cognitive traits with twin
      studies indicating a strong genetic origin. However genes associated with this
      domain are unknown. Our research into the neurodevelopmental disorder Williams
      Beuren syndrome (WBS) has identified a gene within the causative recurrent
      1.5/1.6 Mb heterozygous microdeletion on chromosome 7q11.23, which may be
      involved in executive functioning. Comparative genome array screening of 55 WBS
      patients revealed a larger ~1.8 Mb microdeletion in 18% of cases, which results
      in the loss of an additional gene, the transcription factor GTF2IRD2. The GTF
      gene family of transcription factors (GTF2I, GTF2IRD1 and GTF2IRD2) are all
      highly expressed in the brain, and GTF2I and GTF2IRD1 are involved in the
      pathogenesis of the cognitive and behavioural phenotypes associated with WBS. A
      multi-level analysis of cognitive, behavioural and psychological functioning in
      WBS patients showed that those with slightly larger deletions encompassing
      GTF2IRD2 were significantly more cognitively impaired in the areas of spatial
      functioning, social reasoning, and cognitive flexibility (a form of executive
      functioning). They also displayed significantly more obsessions and externalizing
      behaviours, a likely manifestation of poor cognitive flexibility and executive
      dysfunction. We provide the first evidence for a role for GTF2IRD2 in higher
      level (executive functioning) abilities and highlight the importance of
      integrating detailed molecular characterisation of patients with comprehensive
      neuropsychological profiling to uncover additional genotype-phenotype
      correlations. The identification of specific genes which contribute to executive
      function has important neuropsychological implications in the treatment of
      patients with conditions like WBS, and will allow further studies into their
      mechanism of action.

PMID- 23118871
TI  - Evaluating operational specifications of point-of-care diagnostic tests: a
      standardized scorecard.
AB  - The expansion of HIV antiretroviral therapy into decentralized rural settings
      will increasingly require simple point-of-care (POC) diagnostic tests that can be
      used without laboratory infrastructure and technical skills. New POC test devices
      are becoming available but decisions around which technologies to deploy may be
      biased without systematic assessment of their suitability for decentralized
      healthcare settings. To address this, we developed a standardized, quantitative
      scorecard tool to objectively evaluate the operational characteristics of POC
      diagnostic devices. The tool scores devices on a scale of 1-5 across 30 weighted
      characteristics such as ease of use, quality control, electrical requirements,
      shelf life, portability, cost and service, and provides a cumulative score that
      ranks products against a set of ideal POC characteristics. The scorecard was
      tested on 19 devices for POC CD4 T-lymphocyte cell counting, clinical chemistry
      or hematology testing. Single and multi-parameter devices were assessed in each
      of test categories. The scores across all devices ranged from 2.78 to 4.40 out of
      5. The tool effectively ranked devices within each category (p<0.01) except the
      CD4 and multi-parameter hematology products. The tool also enabled comparison of
      different characteristics between products. Agreement across the four scorers for
      each product was high (intra-class correlation >0.80; p<0.001). Use of this tool
      enables the systematic evaluation of diagnostic tests to facilitate product
      selection and investment in appropriate technology. It is particularly relevant
      for countries and testing programs considering the adoption of new POC diagnostic
      tests.

PMID- 23118872
TI  - Comparative proteomic profiling of human bile reveals SSP411 as a novel biomarker
      of cholangiocarcinoma.
AB  - BACKGROUND: Cholangiocarcinoma (CC) is an intractable cancer, arising from
      biliary epithelial cells, which has a poor prognosis and is increasing in
      incidence. Early diagnosis of CC is essential as surgical resection remains the
      only effective therapy. The purpose of this study was to identify improved
      biomarkers to facilitate early diagnosis and prognostication in CC. METHODS: A
      comparative expression profile of human bile samples from patients with
      cholangitis and CC was constructed using a classic 2D/MS/MS strategy and the
      expression of selected proteins was confirmed by Western blotting.
      Immunohistochemistry was performed to determine the expression levels of selected
      candidate biomarkers in CC and matched normal tissues. Finally, spermatogenesis
      associated 20 (SSP411; also named SPATA20) was quantified in serum samples using
      an ELISA. RESULTS: We identified 97 differentially expressed protein spots,
      corresponding to 49 different genes, of which 38 were upregulated in bile from CC
      patients. Western blotting confirmed that phosphoglycerate mutase 1 (brain) (PGAM
      1), protein disulfide isomerase family A, member 3 (PDIA3), heat shock 60 kDa
      protein 1 (chaperonin) (HSPD1) and SSP411 were significantly upregulated in
      individual bile samples from CC patients. Immunohistochemistry demonstrated these
      proteins were also overexpressed in CC, relative to normal tissues. SSP411
      displayed value as a potential serum diagnostic biomarker for CC, with a
      sensitivity of 90.0% and specificity of 83.3% at a cutoff value of 0.63.
      CONCLUSIONS: We successfully constructed a proteomic profile of CC bile proteins,
      providing a valuable pool novel of candidate biomarkers. SSP411 has potential as
      a biomarker for the diagnosis of CC.

PMID- 23118874
TI  - The role of the bHLH protein hairy in morphogenetic furrow progression in the
      developing Drosophila eye.
AB  - In Drosophila eye development, a wave of differentiation follows a morphogenetic
      furrow progressing across the eye imaginal disc. This is subject to negative
      regulation attributed to the HLH repressor proteins Hairy and Extramacrochaete.
      Recent studies identify negative feedback on the bHLH gene daughterless as one of
      the main functions of extramacrochaete. Here the role of hairy was assessed in
      relation to daughterless and other HLH genes. Hairy was not found to regulate the
      expression of Daughterless, Extramacrochaete or Atonal, and Hairy expression was
      largely unregulated by these other genes. Null alleles of hairy did not alter the
      rate or pattern of differentiation, either alone or in the absence of
      Extramacrochaete. These findings question whether hairy is an important regulator
      of the progression of retinal differentiation in Drosophila, alone or redundantly
      with extramacrochaete.

PMID- 23118873
TI  - Muscarinic and nicotinic modulation of thalamo-prefrontal cortex synaptic
      plasticity [corrected] in vivo.
AB  - The mediodorsal nucleus of the thalamus (MD) is a rich source of afferents to the
      medial prefrontal cortex (mPFC). Dysfunctions in the thalamo-prefrontal
      connections can impair networks implicated in working memory, some of which are
      affected in Alzheimer disease and schizophrenia. Considering the importance of
      the cholinergic system to cortical functioning, our study aimed to investigate
      the effects of global cholinergic activation of the brain on MD-mPFC synaptic
      plasticity by measuring the dynamics of long-term potentiation (LTP) and
      depression (LTD) in vivo. Therefore, rats received intraventricular injections
      either of the muscarinic agonist pilocarpine (PILO; 40 nmol/uL), the nicotinic
      agonist nicotine (NIC; 320 nmol/uL), or vehicle. The injections were administered
      prior to either thalamic high-frequency (HFS) or low-frequency stimulation (LFS).
      Test pulses were applied to MD for 30 min during baseline and 240 min after HFS
      or LFS, while field postsynaptic potentials were recorded in the mPFC. The
      transient oscillatory effects of PILO and NIC were monitored through recording of
      thalamic and cortical local field potentials. Our results show that HFS did not
      affect mPFC responses in vehicle-injected rats, but induced a delayed-onset LTP
      with distinct effects when applied following PILO or NIC. Conversely, LFS induced
      a stable LTD in control subjects, but was unable to induce LTD when applied after
      PILO or NIC. Taken together, our findings show distinct modulatory effects of
      each cholinergic brain activation on MD-mPFC plasticity following HFS and LFS.
      The LTP-inducing action and long-lasting suppression of cortical LTD induced by
      PILO and NIC might implicate differential modulation of thalamo-prefrontal
      functions under low and high input drive.

PMID- 23118875
TI  - FMRI activity in the macaque cerebellum evoked by intracortical microstimulation
      of the primary somatosensory cortex: evidence for polysynaptic propagation.
AB  - Simultaneous electrical microstimulation (EM) and functional magnetic resonance
      imaging (fMRI) is a useful tool for probing connectivity across brain areas in
      vivo. However, it is not clear whether intracortical EM can evoke blood
      oxygenation-level-dependent (BOLD) signal in areas connected polysynaptically to
      the stimulated site. To test for the presence of the BOLD activity evoked by
      polysynaptic propagation of the EM signal, we conducted simultaneous fMRI and EM
      in the primary somatosensory cortex (S1) of macaque monkeys. We in fact observed
      BOLD activations in the contralateral cerebellum which is connected to the
      stimulation site (i.e. S1) only through polysynaptic pathways. Furthermore, the
      magnitude of cerebellar activations was dependent on the current amplitude of the
      EM, confirming the EM is the cause of the cerebellar activations. These results
      suggest the importance of considering polysynaptic signal propagation,
      particularly via pathways including subcortical structures, for correctly
      interpreting 'functional connectivity' as assessed by simultaneous EM and fMRI.

PMID- 23118876
TI  - Clinical relevance of loss of 11p15 in primary and metastatic breast cancer:
      association with loss of PRKCDBP expression in brain metastases.
AB  - The occurrence of brain metastases among breast cancer patients is currently
      rising with approximately 20-25% incidence rates, underlining the importance of
      the identification of new therapeutic and prognostic markers. We have previously
      screened for new markers for brain metastasis by array CGH. We found that loss of
      11p15 is common among these patients. In this study, we investigated the clinical
      significance of loss of 11p15 in primary breast cancer (BC) and breast cancer
      brain metastases (BCBM). 11p15 aberration patterns were assessed by allelic
      imbalance (AI) analysis in primary BC (n = 78), BCBM (n = 21) and metastases from
      other distant sites (n = 6) using six different markers. AI at 11p15 was
      significantly associated with BCBM (p = 0.002). Interestingly, a subgroup of
      primary BC with a later relapse to the brain had almost equally high AI rates as
      the BCBM cases. In primary BC, AI was statistically significantly associated with
      high grade, negative hormone receptor status, and triple-negative (TNBC) tumors.
      Gene expression profiling identified PRKCDBP in the 11p15 region to be
      significantly downregulated in both BCBM and primary BC with brain relapse
      compared to primary tumors without relapse or bone metastasis (fdr<0.05). qRT-PCR
      confirmed these results and methylation was shown to be a common way to silence
      this gene. In conclusion, we found loss at 11p15 to be a marker for TNBC primary
      tumors and BCBM and PRKCDBP to be a potential target gene in this locus.

PMID- 23118877
TI  - Mortality, severe acute respiratory infection, and influenza-like illness
      associated with influenza A(H1N1)pdm09 in Argentina, 2009.
AB  - INTRODUCTION: While there is much information about the burden of influenza
      A(H1N1)pdm09 in North America, little data exist on its burden in South America.
      METHODS: During April to December 2009, we actively searched for persons with
      severe acute respiratory infection and influenza-like illness (ILI) in three
      sentinel cities. A proportion of case-patients provided swabs for influenza
      testing. We estimated the number of case-patients that would have tested positive
      for influenza by multiplying the number of untested case-patients by the
      proportion who tested positive. We estimated rates by dividing the estimated
      number of case-patients by the census population after adjusting for the
      proportion of case-patients with missing illness onset information and ILI case
      patients who visited physicians multiple times for one illness event. RESULTS: We
      estimated that the influenza A(H1N1)pdm09 mortality rate per 100,000 person-years
      (py) ranged from 1.5 among persons aged 5-44 years to 5.6 among persons aged >=
      65 years. A(H1N1)pdm09 hospitalization rates per 100,000 py ranged between 26.9
      among children aged <5 years to 41.8 among persons aged >= 65 years. Influenza
      A(H1N1)pdm09 ILI rates per 100 py ranged between 1.6 among children aged <5 to
      17.1 among persons aged 45-64 years. While 9 (53%) of 17 influenza A(H1N1)pdm09
      decedents with available data had obesity and 7 (17%) of 40 had diabetes, less
      than 4% of surviving influenza A(H1N1)pdm09 case-patients had these pre-existing
      conditions (p <= 0.001). CONCLUSION: Influenza A(H1N1)pdm09 caused a similar
      burden of disease in Argentina as in other countries. Such disease burden
      suggests the potential value of timely influenza vaccinations.

PMID- 23118878
TI  - Differential impact of IL-10 expression on survival and relapse between HPV16
      positive and -negative oral squamous cell carcinomas.
AB  - Human papillomavirus (HPV) is a risk factor in a subset of oropharyngeal cancer;
      however, the contribution of HPV in the malignancy of oral squamous cell
      carcinomas (OSCC) is not fully understood in Taiwanese. Herein, 61 patients with
      no risk factors and 117 patients with one or more risk factors were enrolled in
      this study. HPV16/18 infection rate in non-smokers, non-drinkers and non-betel
      quid chewers was higher than their counterparts. The development of HPV-infected
      cancer has been shown to be associated with interleukin-10 (IL-10) expression. To
      this end, IL-10 mRNA expression in OSCC tumors was evaluated by real-time RT-PCR.
      Data showed that HPV-positive patients had higher IL-10 mRNA levels than in HPV
      negative patients. Kaplan-Meier and Cox-regression analysis indicated that the
      prognostic significance of IL-10 mRNA on overall survival and relapse free
      survival was only observed in HPV-positive OSCC, but not in HPV-negative OSCC.
      Mechanistically, the elevation of IL-10 by E6 was responsible for increased
      colony formation and migration capability in OSCC cells. Therefore, we suggest
      that IL-10 induced by E6 promotes cell growth and migration capability and
      consequent poor survival and relapse in HPV-positive OSCC.

PMID- 23118879
TI  - Endogenous opioids in wound-site neutrophils of sternotomy patients.
AB  - BACKGROUND: Postoperative pain management is a critical aspect of patient care.
      The inflammatory state of the post-sternotomy surgical wound sensitizes nerve
      endings, causing pain. Unrelieved or improperly managed pain compromises wound
      healing. Peripheral opioid receptors play a major role in analgesia, particularly
      under inflammatory conditions where both opioid receptor expression and efficacy
      are increased. Leukocytic opioid peptides include beta-endorphin (END), met
      enkephalin (ENK), and dynorphin-A (DYN), with END and ENK being predominant.
      METHODOLOGY/PRINCIPAL FINDINGS: This work represents the first study of
      inflammatory cells collected from post-sternotomy wounds of patients undergoing
      cardiac surgery including coronary artery bypass grafting (CABG). Wound fluid
      (WF) and cells were collected from sternal wounds using a JP Blake drain at 24,
      48, and 72 hours post sternum closure. Anti-CD15 staining and flow cytometry
      revealed that polymorphonuclear neutrophils (PMN) are the predominant cells
      present in wound fluid collected post-surgery. Compared to peripheral blood (PB)
      derived PMN, significant increases in CD177+/CD66b+ PMN were observed suggesting
      activation of wound-site PMN. Such activation was associated with higher levels
      of opioid peptide expression in PMN derived from WF. Indeed, increased level of
      opioid peptides in sternal wound environment was noted 72 h post-surgery. We
      demonstrate that WF contains factors that can significantly induce POMC
      transcription in human PMNs. IL-10 and IL-4 were abundant in WF and both
      cytokines significantly induced POMC gene expression suggesting that WF factors
      such as IL-10 and IL-4 contribute towards increased opioid peptide expression in
      wound-site PMN. CONCLUSIONS/SIGNIFICANCE: This approach provided a unique
      opportunity to study the cross-talk between inflammation and opioid peptides in
      PMN at a sternotomy wound-site. Wound-site PMN exhibited induction of END and
      ENK. In addition, sternal wound fluid significantly induced END expression in
      PMN. Taken together, these data constitute first clinical evidence that human
      wound-site PMNs are direct contributors of opioids at the sternal wound-site.

PMID- 23118880
TI  - The balance of apoptotic and necrotic cell death in Mycobacterium tuberculosis
      infected macrophages is not dependent on bacterial virulence.
AB  - BACKGROUND: An important mechanism of Mycobacterium tuberculosis pathogenesis is
      the ability to control cell death pathways in infected macrophages: apoptotic
      cell death is bactericidal, whereas necrotic cell death may facilitate bacterial
      dissemination and transmission. METHODS: We examine M.tuberculosis control of
      spontaneous and chemically induced macrophage cell death using automated confocal
      fluorescence microscopy, image analysis, flow cytometry, plate-reader based
      vitality assays, and M.tuberculosis strains including H37Rv, and isogenic
      virulent and avirulent strains of the Beijing lineage isolate GC1237. RESULTS: We
      show that bacterial virulence influences the dynamics of caspase activation and
      the total level of cytotoxicity. We show that the powerful ability of
      M.tuberculosis to inhibit exogenously stimulated apoptosis is abrogated by loss
      of virulence. However, loss of virulence did not influence the balance of
      macrophage apoptosis and necrosis--both virulent and avirulent isogenic strains
      of GC1237 induced predominantly necrotic cell death compared to H37Rv which
      induced a higher relative level of apoptosis. CONCLUSIONS: This reveals that
      macrophage necrosis and apoptosis are independently regulated during M.
      tuberculosis infection of macrophages. Virulence affects the level of host cell
      death and ability to inhibit apoptosis but other strain-specific characteristics
      influence the ultimate mode of host cell death and alter the balance of apoptosis
      and necrosis.

PMID- 23118881
TI  - Modeling 18F-FDG kinetics during acute lung injury: experimental data and
      estimation errors.
AB  - BACKGROUND: There is increasing interest in Positron Emission Tomography (PET) of
      2-deoxy-2-[18F]flouro-D-glucose ((18)F-FDG) to evaluate pulmonary inflammation
      during acute lung injury (ALI). We assessed the effect of extra-vascular lung
      water on estimates of (18)F-FDG-kinetics parameters in experimental and simulated
      data using the Patlak and Sokoloff methods, and our recently proposed four
      compartment model. METHODOLOGY/PRINCIPAL FINDINGS: Eleven sheep underwent
      unilateral lung lavage and 4 h mechanical ventilation. Five sheep received
      intravenous endotoxin (10 ng/kg/min). Dynamic (18)F-FDG PET was performed at the
      end of the 4 h period. (18)F-FDG net uptake rate (Ki), phosphorylation rate
      (k(3)), and volume of distribution (F(e)) were estimated in three
      isogravitational regions for each method. Simulations of normal and ALI (18)F-FDG
      kinetics were conducted to study the dependence of estimated parameters on the
      transport rate constants to (k(5)) and from (k(6)) the extra-vascular extra
      cellular compartment. The four-compartment model described 85.7% of the studied
      (18)F-FDG-kinetics better than the Sokoloff model. Relative to the four
      compartment model the Sokoloff model exhibited a consistent positive bias in Ki
      (3.32 [1.30-5.65] 10(-4)/min, p<0.001) and showed inaccurate estimates of the
      parameters composing Ki (k(3) and F(e)), even when Ki was similar for those
      methods. In simulations, errors in estimates of Ki due to the extra-vascular
      extra-cellular compartment depended on both k(5) and k(5)/k(6), with errors for
      the Patlak and Sokoloff methods of 0.02 [-0.01-0.18] and 0.40 [0.18-0.60] 10(
      3)/min for normal lungs and of -0.47 [-0.89-0.72] and 2.35 [0.85-3.68] 10(-3)/min
      in ALI. CONCLUSIONS/SIGNIFICANCE: (18)F-FDG accumulation in lung extra-vascular
      fluid, which is commonly increased during lung injury, can result in substantial
      estimation errors using the traditional Patlak and Sokoloff methods. These errors
      depend on the extra-vascular extra-cellular compartment volume and its transport
      rates with other compartments. The four-compartment model provides more accurate
      quantification of (18)F-FDG-kinetics than those methods in the presence of
      increased extra-vascular fluid.

PMID- 23118882
TI  - HIV-1 subtypes and recombinants in Northern Tanzania: distribution of viral
      quasispecies.
AB  - This study analyzed the distribution and prevalence of HIV-1 subtypes,
      multiplicity of HIV-1 infection, and frequency of inter-subtype recombination
      among HIV-1-infected female bar and hotel workers in Moshi, Kilimanjaro Region,
      Tanzania, from 2004 to 2007. The HIV-1 viral sequences spanning the V1-C5 region
      of HIV-1 env gp120 were analyzed from 50 subjects by single genome amplification
      and sequencing (SGA/S) technique. A total of 1740 sequences were amplified and
      sequenced from the HIV-1 proviral DNA template. The median env sequences analyzed
      per subject per two time points was 38 (IQR 28-50) over one year of HIV
      infection. In a subset of 14 subjects, a total of 239 sequences were obtained
      from HIV-1 RNA template at the baseline visit. The most prevalent HIV-1 subtypes
      were A1 (56%) and C (30%), while HIV-1 subtype D and inter-subtype recombinant
      viruses were found in 6% and 8% of subjects respectively. Transmission of
      multiple HIV-1 variants was evident in 27% of the subjects infected with pure HIV
      1 subtypes A1, C, or D. The HIV-1 inter-subtype recombinants were found in 8%
      including HIV-1 C/A, D/A, and complex mosaic recombinants. Multiple viral
      variants were found in two subjects infected with inter-subtype recombinants. One
      subject harbored quasispecies of both pure HIV-1 A1 and C/A recombinant. The
      other subject was infected with two complex mosaic inter-subtype recombinant
      variants belonging to subtype D. HIV-1 multiple infections and ongoing
      recombination contribute significantly to the genetic diversity of circulating
      HIV-1 in Tanzania and have important implications for vaccine design and the
      development of therapeutic strategies.

PMID- 23118883
TI  - Experimental test of spatial updating models for monkey eye-head gaze shifts.
AB  - How the brain maintains an accurate and stable representation of visual target
      locations despite the occurrence of saccadic gaze shifts is a classical problem
      in oculomotor research. Here we test and dissociate the predictions of different
      conceptual models for head-unrestrained gaze-localization behavior of macaque
      monkeys. We adopted the double-step paradigm with rapid eye-head gaze shifts to
      measure localization accuracy in response to flashed visual stimuli in darkness.
      We presented the second target flash either before (static), or during (dynamic)
      the first gaze displacement. In the dynamic case the brief visual flash induced a
      small retinal streak of up to about 20 deg at an unpredictable moment and retinal
      location during the eye-head gaze shift, which provides serious challenges for
      the gaze-control system. However, for both stimulus conditions, monkeys localized
      the flashed targets with accurate gaze shifts, which rules out several models of
      visuomotor control. First, these findings exclude the possibility that gaze-shift
      programming relies on retinal inputs only. Instead, they support the notion that
      accurate eye-head motor feedback updates the gaze-saccade coordinates. Second, in
      dynamic trials the visuomotor system cannot rely on the coordinates of the
      planned first eye-head saccade either, which rules out remapping on the basis of
      a predictive corollary gaze-displacement signal. Finally, because gaze-related
      head movements were also goal-directed, requiring continuous access to eye-in
      head position, we propose that our results best support a dynamic feedback scheme
      for spatial updating in which visuomotor control incorporates accurate signals
      about instantaneous eye- and head positions rather than relative eye- and head
      displacements.

PMID- 23118884
TI  - Apparent defect in yeast bud-site selection due to a specific failure to splice
      the pre-mRNA of a regulator of cell-type-specific transcription.
AB  - The yeast Saccharomyces cerevisiae normally selects bud sites (and hence axes of
      cell polarization) in one of two distinct patterns, the axial pattern of haploid
      cells and the bipolar pattern of diploid cells. Although many of the proteins
      involved in bud-site selection are known, it is likely that others remain to be
      identified. Confirming a previous report (Ni and Snyder, 2001, Mol. Biol. Cell
      12, 2147-2170), we found that diploids homozygous for deletions of IST3/SNU17 or
      BUD13 do not show normal bipolar budding. However, these abnormalities do not
      reflect defects in the apparatus of bipolar budding. Instead, the absence of Ist3
      or Bud13 results in a specific defect in the splicing of the MATa1 pre-mRNA,
      which encodes a repressor that normally blocks expression of haploid-specific
      genes in diploid cells. When Mata1 protein is lacking, Axl1, a haploid-specific
      protein critical for the choice between axial and bipolar budding, is expressed
      ectopically in diploid cells and disrupts bipolar budding. The involvement of
      Ist3 and Bud13 in pre-mRNA splicing is by now well known, but the degree of
      specificity shown here for MATa1 pre-mRNA, which has no obvious basis in the pre
      mRNA structure, is rather surprising in view of current models for the functions
      of these proteins. Moreover, we found that deletion of PML1, whose product is
      thought to function together with Ist3 and Bud13 in a three-protein retention-and
      splicing (RES) complex, had no detectable effect on the splicing in vivo of
      either MATa1 or four other pre-mRNAs.

PMID- 23118885
TI  - Mucosal immunization with live attenuated Francisella novicida U112DeltaiglB
      protects against pulmonary F. tularensis SCHU S4 in the Fischer 344 rat model.
AB  - The need for an efficacious vaccine against Francisella tularensis is a
      consequence of its low infectious dose and high mortality rate if left untreated.
      This study sought to characterize a live attenuated subspecies novicida-based
      vaccine strain (U112DeltaiglB) in an established second rodent model of pulmonary
      tularemia, namely the Fischer 344 rat using two distinct routes of vaccination
      (intratracheal [i.t.] and oral). Attenuation was verified by comparing
      replication of U112DeltaiglB with wild type parental strain U112 in F344 primary
      alveolar macrophages. U112DeltaiglB exhibited an LD(50)>10(7) CFU compared to the
      wild type (LD(50) = 5 * 10(6) CFU i.t.). Immunization with 10(7) CFU
      U112DeltaiglB by i.t. and oral routes induced antigen-specific IFN-gamma and
      potent humoral responses both systemically (IgG2a>IgG1 in serum) and at the site
      of mucosal vaccination (respiratory/intestinal compartment). Importantly,
      vaccination with U112DeltaiglB by either i.t. or oral routes provided equivalent
      levels of protection (50% survival) in F344 rats against a subsequent pulmonary
      challenge with ~25 LD(50) (1.25 * 10(4) CFU) of the highly human virulent strain
      SCHU S4. Collectively, these results provide further evidence on the utility of a
      mucosal vaccination platform with a defined subsp. novicida U112DeltaiglB vaccine
      strain in conferring protective immunity against pulmonary tularemia.

PMID- 23118886
TI  - Sequence evolution of the intrinsically disordered and globular domains of a
      model viral oncoprotein.
AB  - In the present work, we have used the papillomavirus E7 oncoprotein to pursue
      structure-function and evolutionary studies that take into account intrinsic
      disorder and the conformational diversity of globular domains. The intrinsically
      disordered (E7N) and globular (E7C) domains of E7 show similar degrees of
      conservation and co-evolution. We found that E7N can be described in terms of
      conserved and coevolving linear motifs separated by variable linkers, while
      sequence evolution of E7C is compatible with the known homodimeric structure yet
      suggests other activities for the domain. Within E7N, inter-residue relationships
      such as residue co-evolution and restricted intermotif distances map functional
      coupling and co-occurrence of linear motifs that evolve in a coordinate manner.
      Within E7C, additional cysteine residues proximal to the zinc-binding site may
      allow redox regulation of E7 function. Moreover, we describe a conserved binding
      site for disordered domains on the surface of E7C and suggest a putative target
      linear motif. Both homodimerization and peptide binding activities of E7C are
      also present in the distantly related host PHD domains, showing that these two
      proteins share not only structural homology but also functional similarities, and
      strengthening the view that they evolved from a common ancestor. Finally, we
      integrate the multiple activities and conformations of E7 into a hierarchy of
      structure-function relationships.

PMID- 23118887
TI  - Non-specific abdominal pain and air pollution: a novel association.
AB  - BACKGROUND: We studied whether short-term exposure to air pollution was
      associated with non-specific abdominal pain in epidemiologic and animal studies.
      METHODS: Patients visiting the emergency department with non-specific abdominal
      pain were identified in Edmonton (1992 to 2002, n = 95,173) and Montreal (1997 to
      2002, n = 25,852). We calculated the daily concentrations for ozone (O(3)),
      nitrogen dioxide (NO(2)), sulfur dioxide (SO(2)), carbon monoxide (CO), and
      particles <10 (PM(10)) or <2.5 (PM(2.5)) um. A case crossover study design was
      used to estimate the odds ratio (OR) and 95% confidence interval (CI) associated
      with an increase in the interquartile range of the air pollutants. We
      investigated differential effects by age and sex. Mice were gavaged with urban
      particle extracts. In animal models, colonic motility was tested, and visceral
      abdominal pain was measured using a writhing test, and behavioral response to oil
      of mustard and neostigmine. Motility and pain was measured acutely (1.5 hours
      after gavage) and chronically (7-days and 21-days after gavage). RESULTS:
      Emergency department visits for non-specific abdominal pain were primarily by
      women between the ages of 15-24 years. Individuals aged 15 to 24 years were at
      increased risk of non-specific abdominal pain in Edmonton (same day CO: OR =
      1.04, 95% CI = 1.02-1.06; and NO(2): OR = 1.06, 95% CI = 1.03-1.09). The risk of
      air pollution among 15-24 year olds in Montreal was significantly positive (same
      day CO: OR = 1.11, 95% CI = 1.05-1.17; NO(2): OR = 1.09, 95% CI = 1.01-1.16;
      SO(2): OR = 1.17, 95% CI = 1.10-1.25; PM(2.5): OR = 1.09, 95% CI = 1.04-1.15).
      Abdominal pain was increased by an acute gavage of pollution extract but not to
      chronic exposure to pollutants. Colonic transit was delayed following chronic but
      not acute exposure with the pollutants. CONCLUSIONS: Epidemiological and animal
      data suggest that short-term exposure to air pollution may trigger non-specific
      abdominal pain in young individuals.

PMID- 23118888
TI  - Combined mitochondrial and nuclear markers revealed a deep vicariant history for
      Leopoldamys neilli, a cave-dwelling rodent of Thailand.
AB  - BACKGROUND: Historical biogeography and evolutionary processes of cave taxa have
      been widely studied in temperate regions. However, Southeast Asian cave
      ecosystems remain largely unexplored despite their high scientific interest. Here
      we studied the phylogeography of Leopoldamys neilli, a cave-dwelling murine
      rodent living in limestone karsts of Thailand, and compared the molecular
      signature of mitochondrial and nuclear markers. METHODOLOGY/PRINCIPAL FINDINGS:
      We used a large sampling (n = 225) from 28 localities in Thailand and a
      combination of mitochondrial and nuclear markers with various evolutionary rates
      (two intronic regions and 12 microsatellites). The evolutionary history of L.
      neilli and the relative role of vicariance and dispersal were investigated using
      ancestral range reconstruction analysis and Approximate Bayesian computation
      (ABC). Both mitochondrial and nuclear markers support a large-scale population
      structure of four main groups (west, centre, north and northeast) and a strong
      finer structure within each of these groups. A deep genealogical divergence among
      geographically close lineages is observed and denotes a high population
      fragmentation. Our findings suggest that the current phylogeographic pattern of
      this species results from the fragmentation of a widespread ancestral population
      and that vicariance has played a significant role in the evolutionary history of
      L. neilli. These deep vicariant events that occurred during Plio-Pleistocene are
      related to the formation of the Central Plain of Thailand. Consequently, the
      western, central, northern and northeastern groups of populations were
      historically isolated and should be considered as four distinct Evolutionarily
      Significant Units (ESUs). CONCLUSIONS/SIGNIFICANCE: Our study confirms the
      benefit of using several independent genetic markers to obtain a comprehensive
      and reliable picture of L. neilli evolutionary history at different levels of
      resolution. The complex genetic structure of Leopoldamys neilli is supported by
      congruent mitochondrial and nuclear markers and has been influenced by the
      geological history of Thailand during Plio-Pleistocene.

PMID- 23118889
TI  - Rhizobia with 16S rRNA and nifH similar to Mesorhizobium huakuii but Novel recA,
      glnII, nodA and nodC genes are symbionts of New Zealand Carmichaelinae.
AB  - New Zealand became geographically isolated about 80 million years ago and this
      separation gave rise to a unique native flora including four genera of legume,
      Carmichaelia, Clianthus and Montigena in the Carmichaelinae clade, tribe
      Galegeae, and Sophora, tribe Sophoreae, sub-family Papilionoideae. Ten bacterial
      strains isolated from NZ Carmichaelinae growing in natural ecosystems grouped
      close to the Mesorhizobium huakuii type strain in relation to their 16S rRNA and
      nifH gene sequences. However, the ten strains separated into four groups on the
      basis of their recA and glnII sequences: all groups were clearly distinct from
      all Mesorhizobium type strains. The ten strains separated into two groups on the
      basis of their nodA sequences but grouped closely together in relation to nodC
      sequences; all nodA and nodC sequences were novel. Seven strains selected and the
      M. huakuii type strain (isolated from Astragalus sinicus) produced functional
      nodules on Carmichaelia spp., Clianthus puniceus and A. sinicus but did not
      nodulate two Sophora species. We conclude that rhizobia closely related to M.
      huakuii on the basis of 16S rRNA and nifH gene sequences, but with variable recA
      and glnII genes and novel nodA and nodC genes, are common symbionts of NZ
      Carmichaelinae.

PMID- 23118890
TI  - A new family of cumulative indexes for measuring scientific performance.
AB  - In this paper we propose a new family of cumulative indexes for measuring
      scientific performance which can be applied to many metrics, including h index
      and its variants (here we apply it to the h index, h(2) index and Google
      Scholar's i10 index). These indexes follow the general principle of repeating the
      index calculation for the same publication set. Using bibliometric data and
      reviewer scores for accepted and rejected fellowship applicants we examine how
      valid the cumulative variant is compared to the original variant. These analyses
      showed that the cumulative indexes result in higher correlations with the
      reviewer scores than their original variants. Thus, the cumulative indexes better
      reflect the assessments by peers than the original variants and are useful
      extensions of the original indexes. In contrast to many other measures of
      scientific performance proposed up to now, the cumulative indexes seem not only
      to be effective, but they are also easy to understand and calculate.

PMID- 23118891
TI  - Serial non-invasive measurements of dermal carotenoid concentrations in dairy
      cows following recovery from abomasal displacement.
AB  - Maintaining the health of farm animals forms the basis for a sustainable and
      profitable production of food from animal origin. Recently, the effects of
      carotenoids on the oxidative status as well as on reproductive and immune
      functions in cattle have been demonstrated. The present study aimed at
      investigating dermal carotenoid levels in cattle recovering from abomasal
      displacement. For this purpose, serial in vivo measurements were undertaken using
      a miniaturized scanner system that relies on reflection spectroscopy (Opsolution
      GmbH, Kassel, Germany). In a first trial, repeated measurements of dermal
      carotenoid concentrations were performed on the udder skin of healthy non
      lactating cattle (n = 6) for one month in weekly intervals. In a second trial, in
      vivo dermal carotenoid concentrations were determined in intervals in 23 cows
      following surgical treatment of abomasal displacement. The results show that
      dermal carotenoid concentrations, determined on a weekly basis over a period of
      one month, showed variations of up to 18% in the healthy individuals kept under
      constant conditions with respect to housing and nutrition. Repeated measurements
      during the recovery period following surgical treatment of abomasal displacement
      resulted in an increase in dermal carotenoid concentrations in 18 of 20 animals
      with a favourable outcome when compared with results obtained within 12 hours
      following surgery. The mean increase in dermal carotenoid concentrations in
      subsequent measurements was 53 +/- 44%, whereas levels decreased (mean 31 +/-
      27%) in cattle with a fatal outcome.These results indicate potential applications
      for reflection spectroscopy for non-invasive early detection of changes in the
      dermal carotenoid concentrations as a reflection of the antioxidant status in an
      animal.

PMID- 23118892
TI  - Comparative phylogeography in Fijian coral reef fishes: a multi-taxa approach
      towards marine reserve design.
AB  - Delineating barriers to connectivity is important in marine reserve design as
      they describe the strength and number of connections among a reserve's
      constituent parts, and ultimately help characterize the resilience of the system
      to perturbations at each node. Here we demonstrate the utility of multi-taxa
      phylogeography in the design of a system of marine protected areas within Fiji.
      Gathering mtDNA control region data from five species of coral reef fish in five
      genera and two families, we find a range of population structure patterns, from
      those experiencing little (Chrysiptera talboti, Halichoeres hortulanus, and
      Pomacentrus maafu), to moderate (Amphiprion barberi, Phi(st) = 0.14 and
      Amblyglyphidodon orbicularis Phi(st) = 0.05) barriers to dispersal. Furthermore
      estimates of gene flow over ecological time scales suggest species-specific,
      asymmetric migration among the regions within Fiji. The diversity among species
      specific results underscores the limitations of generalizing from single-taxon
      studies, including the inability to differentiate between a species-specific
      result and a replication of concordant phylogeographic patterns, and suggests
      that greater taxonomic coverage results in greater resolution of community
      dynamics within Fiji. Our results indicate that the Fijian reefs should not be
      managed as a single unit, and that closely related species can express
      dramatically different levels of population connectivity.

PMID- 23118893
TI  - Circulating thyroxine, thyroid-stimulating hormone, and hypothyroid status and
      the risk of prostate cancer.
AB  - BACKGROUND: Thyroid hormones may influence risk of cancer through their role in
      cell differentiation, growth, and metabolism. One study of circulating thyroid
      hormones supports this hypothesis with respect to prostate cancer. We undertook a
      prospective analysis of thyroid hormones and prostate cancer risk in the Alpha
      Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. METHODS: Within the
      ATBC Study, a randomized controlled trial of alpha-tocopherol and beta-carotene
      supplements and cancer incidence in male smokers, 402 prostate cancer cases were
      sampled. Controls were matched 2:1 to cases on age and date of blood collection.
      Odds ratios (OR) and 95% confidence intervals (CI) of prostate cancer were
      estimated for quintiles of serum total and free thyroxine (T4), thyroid
      stimulating hormone (TSH), thyroid-binding globulin (TBG), and by categories of
      thyroid status. RESULTS: Men with serum higher TSH had a decreased risk of
      prostate cancer compared to men with lower TSH (Q5 vs. Q1-4: OR = 0.70, 95% CI:
      0.51-0.97, p = 0.03). When the T4 and TSH measurements were combined to define
      men as hypothyroid, euthyroid or hyperthyroid, hypothyroid men had a lower risk
      of prostate cancer compared to euthyroid men (OR = 0.48, 95% CI = 0.28-0.81, p =
      0.006). We observed no association between hyperthyroid status and risk, although
      the number of hyperthyroid men with prostate cancer was small (n = 9).
      CONCLUSIONS: In this prospective study of smokers, men with elevated TSH and
      those classified as being in a hypothyroid state were at decreased risk of
      prostate cancer. Future studies should examine the association in other
      populations, particularly non-smokers and other racial/ethnic groups.

PMID- 23118894
TI  - Human papillomavirus infection in HIV-1 infected women in Catalonia (Spain):
      implications for prevention of cervical cancer.
AB  - BACKGROUND: High-risk human Papillomavirus infection is a necessary factor for
      cervical squamous intraepithelial lesions and invasive cervical cancer. In HIV-1
      infected women, HPV infection is more prevalent and a higher risk of cervical
      cancer has been identified. We aimed to calculate the prevalence of infection by
      HR-HPV, determine the factors associated with this infection and abnormal
      cytology findings and to describe the history of cervical cancer screening in HIV
      1-infected women. METHODS: We enrolled 479 HIV-1-infected women from the PISCIS
      cohort. Each patient underwent a gynecological check-up, PAP smear, HPV AND
      Hybrid capture, HPV genotyping, and colposcopy and biopsy, if necessary. We
      applied questionnaires to obtain information on sociodemographic, behavioral,
      clinical, and cervical screening variables. We present a cross-sectional
      analysis. RESULTS: Median age was 42 years. The prevalence of HR-HPV infection
      was 33.2% and that of high-grade squamous intraepithelial lesions (HSIL) was
      3.8%. The most common genotypes were 16(23%), 53(20.3%), and 52(16.2%). The
      factor associated with HR-HPV infection was age <30 years (odds ratio[OR],2.5;
      95%confidence interval[CI],1.1-5.6). The factors associated with the presence of
      HSIL or low-grade squamous intraepithelial lesions (LSIL) were CD4T-lymphocyte
      count <200 cells/mm(3) versus >500 cells/mm(3) (OR,8.4; 95%CI,3.7-19.2), HIV-1
      viral load >10,000 copies/mL versus <400 copies/mL (OR,2.1; 95%CI,1.0-4.4), and
      use of oral contraceptives (OR,2.0; 95%CI,1.0-3.9). Sixty percent of HIV-1
      infected women had had one Pap smear within the last 2 years. CONCLUSIONS: The
      high prevalence of HPV infection and cervical lesions in the HIV-1-infected
      population in Catalonia, as well as the low coverage and frequency of screening
      in this group, means that better preventive efforts are necessary and should
      include vaccination against HPV, better accessibility to screening programs,
      training of health care professionals, and specific health education for HIV-1
      infected women.

PMID- 23118895
TI  - Are risk factors common to thyroid cancer and nodule? A forty years observational
      time-trend study.
AB  - A progressive increase in the incidence of thyroid cancer (TC) has been reported
      over the last few decades. This either reflects the increased number of newly
      discovered and accurately selected thyroid nodules with more sensitive
      technologies and a relative more potent carcinogenic effect of pathogenetic
      factors in malignant, but not benign nodules. This observational time-trend study
      addresses this issue by analysing the proportion of TC within 8411 consecutive
      thyroid nodule (TN) patients evaluated in Pisa by the same pathology Department
      and individual clinician over a four-decade period. From 1972 to 1979 surgery was
      used to detect TC among the TN patients: 1140 TN patients were operated on and 35
      cancers were detected (3.1% of all the TN patients). Subsequently, needle
      aspiration techniques were used to select TN for surgery. From 1980 to 1992, 5403
      TN patients were examined, 483 were selected for surgery, and 150 cancers were
      found (2.8% of all the TN patients). From 1993 to 2010, 1568 TN patients were
      examined, 143 were selected for surgery, and 46 cancers were found (2.9% of all
      the TN patients). Therefore, in the University Hospital of Pisa, and independent
      of preoperative TN selection protocols, these proportions of TN eventually found
      to harbor TC remained statistically unchanged over 40 years (p = 0.810). This
      finding suggests that pathogenic risk factors and more sensitive diagnostic
      technologies did not differentially affect the incidence of TN and TC.

PMID- 23118897
TI  - Humans as animal sentinels for forecasting asthma events: helping health services
      become more responsive.
AB  - The concept of forecasting asthma using humans as animal sentinels is uncommon.
      This study explores the plausibility of predicting future asthma daily admissions
      using retrospective data in London (2005-2006). Negative binomial regressions
      were used in modeling; allowing the non-contiguous autoregressive components.
      Selected lags were based on partial autocorrelation function (PACF) plot with a
      maximum lag of 7 days. The model was contrasted with naive historical and
      seasonal models. All models were cross validated. Mean daily asthma admission in
      2005 was 27.9 and in 2006 it was 28.9. The lags 1, 2, 3, 6 and 7 were
      independently associated with daily asthma admissions based on their PACF plots.
      The lag model prediction of peak admissions were often slightly out of
      synchronization with the actual data, but the days of greater admissions were
      better matched than the days of lower admissions. A further investigation across
      various populations is necessary.

PMID- 23118896
TI  - RanBPM is an inhibitor of ERK signaling.
AB  - Ran-binding protein M (RanBPM) is a nucleocytoplasmic protein of yet unknown
      function. We have previously shown that RanBPM inhibits expression of the anti
      apoptotic factor Bcl-2 and promotes apoptosis induced by DNA damage. Here we show
      that the effects of RanBPM on Bcl-2 expression occur through a regulation of the
      ERK signaling pathway. Transient and stable down-regulation of RanBPM stimulated
      ERK phosphorylation, leading to Bcl-2 up-regulation, while re-expression of
      RanBPM reversed these effects. RanBPM was found to inhibit MEK and ERK activation
      induced by ectopic expression of active RasV12. Activation of ERK by active c-Raf
      was also prevented by RanBPM. Expression of RanBPM correlated with a marked
      decrease in the protein levels of ectopically expressed active c-Raf and also
      affected the expression of endogenous c-Raf. RanBPM formed a complex with both
      active c-Raf, consisting of the C-terminal kinase domain, and endogenous c-Raf in
      mammalian cells. In addition, RanBPM was found to decrease the binding of Hsp90
      to c-Raf. Finally, we show that loss of RanBPM expression confers increased cell
      proliferation and cell migration properties to HEK293 cells. Altogether, these
      findings establish RanBPM as a novel inhibitor of the ERK pathway through an
      interaction with the c-Raf complex and a regulation of c-Raf stability, and
      provide evidence that RanBPM loss of expression results in constitutive
      activation of the ERK pathway and promotes cellular events leading to cellular
      transformation and tumorigenesis.

PMID- 23118898
TI  - Role of disulfide cross-linking of mutant SOD1 in the formation of inclusion-body
      like structures.
AB  - BACKGROUND: Pathologic aggregates of superoxide dismutase 1 (SOD1) harboring
      mutations linked to familial amyotrophic lateral sclerosis (fALS) have been shown
      to contain aberrant intermolecular disulfide cross-links. In prior studies, we
      observed that intermolecular bonding was not necessary in the formation of
      detergent- insoluble SOD1 complexes by mutant SOD1, but we were unable to assess
      whether this type of bonding may be important for pathologic inclusion formation.
      In the present study, we visually assess the formation of large inclusions by
      fusing mutant SOD1 to yellow fluorescent protein (YFP). METHODOLOGY/PRINCIPAL
      FINDINGS: Experimental constructs possessing mutations at all cysteine residues
      in SOD1 (sites 6, 57, 111, and 146 to F,S,Y,R or G,S,Y,R, respectively) were
      shown to maintain a high propensity of inclusion formation despite the inability
      to form disulfide cross-links. Interestingly, although aggregates form when all
      cysteines were mutated, double mutants of the ALS mutation C6G with an
      experimental mutation C111S exhibited low aggregation propensity.
      CONCLUSIONS/SIGNIFICANCE: Overall, this study is an extension of previous work
      demonstrating that cysteine residues in mutant SOD1 play a role in modulating
      aggregation and that intermolecular disulfide bonds are not required to produce
      large intracellular inclusion-like structures.

PMID- 23118900
TI  - Explaining spatial heterogeneity in population dynamics and genetics from spatial
      variation in resources for a large herbivore.
AB  - Fine-scale spatial variation in genetic relatedness and inbreeding occur across
      continuous distributions of several populations of vertebrates; however, the
      basis of observed variation is often left untested. Here we test the hypothesis
      that prior observations of spatial patterns in genetics for an island population
      of feral horses (Sable Island, Canada) were the result of spatial variation in
      population dynamics, itself based in spatial heterogeneity in underlying habitat
      quality. In order to assess how genetic and population structuring related to
      habitat, we used hierarchical cluster analysis of water sources and an indicator
      analysis of the availability of important forage species to identify a
      longitudinal gradient in habitat quality along the length of Sable Island. We
      quantify a west-east gradient in access to fresh water and availability of two
      important food species to horses: sandwort, Honckenya peploides, and beach pea,
      Lathyrus japonicas. Accordingly, the population clusters into three groups that
      occupy different island segments (west, central, and east) that vary markedly in
      their local dynamics. Density, body condition, and survival and reproduction of
      adult females were highest in the west, followed by central and east areas. These
      results mirror a previous analysis of genetics, which showed that inbreeding
      levels are highest in the west (with outbreeding in the east), and that there are
      significant differences in fixation indices among groups of horses along the
      length of Sable Island. Our results suggest that inbreeding depression is not an
      important limiting factor to the horse population. We conclude that where habitat
      gradients exist, we can anticipate fine-scale heterogeneity in population
      dynamics and hence genetics.

PMID- 23118899
TI  - Natural variation in the VELVET gene bcvel1 affects virulence and light-dependent
      differentiation in Botrytis cinerea.
AB  - Botrytis cinerea is an aggressive plant pathogen causing gray mold disease on
      various plant species. In this study, we identified the genetic origin for
      significantly differing phenotypes of the two sequenced B. cinerea isolates,
      B05.10 and T4, with regard to light-dependent differentiation, oxalic acid (OA)
      formation and virulence. By conducting a map-based cloning approach we identified
      a single nucleotide polymorphism (SNP) in an open reading frame encoding a VELVET
      gene (bcvel1). The SNP in isolate T4 results in a truncated protein that is
      predominantly found in the cytosol in contrast to the full-length protein of
      isolate B05.10 that accumulates in the nuclei. Deletion of the full-length gene
      in B05.10 resulted in the T4 phenotype, namely light-independent conidiation,
      loss of sclerotial development and oxalic acid production, and reduced virulence
      on several host plants. These findings indicate that the identified SNP
      represents a loss-of-function mutation of bcvel1. In accordance, the expression
      of the B05.10 copy in T4 rescued the wild-type/B05.10 phenotype. BcVEL1 is
      crucial for full virulence as deletion mutants are significantly hampered in
      killing and decomposing plant tissues. However, the production of the two best
      known secondary metabolites, the phytotoxins botcinic acid and botrydial, are not
      affected by the deletion of bcvel1 indicating that other factors are responsible
      for reduced virulence. Genome-wide expression analyses of B05.10- and Deltabcvel1
      infected plant material revealed a number of genes differentially expressed in
      the mutant: while several protease- encoding genes are under-expressed in
      Deltabcvel1 compared to the wild type, the group of over-expressed genes is
      enriched for genes encoding sugar, amino acid and ammonium transporters and
      glycoside hydrolases reflecting the response of Deltabcvel1 mutants to nutrient
      starvation conditions.

PMID- 23118902
TI  - Significantly reducing post-tonsillectomy haemorrhage requiring surgery by
      suturing the faucial pillars: a retrospective analysis.
AB  - BACKGROUND: The tonsillectomy is one of the most frequently performed surgical
      procedures. Given the comparatively frequent postsurgical bleeding associated
      with this procedure, particular attention has been paid to reduction of the
      postoperative bleeding rate. In 2006, we introduced routine suturing of the
      faucial pillars at our clinic to reduce postoperative haemorrhage. METHODS: Two
      groups from the years 2003-2005 (n = 1000) and 2007-2009 (n = 1000) have been
      compared. We included all patients who had an elective tonsillectomy due to a
      benign, non-acute inflammatory tonsil illness. In the years 2007-2009, we
      additionally sutured the faucial pillars after completing haemostasis. For
      primary haemostasis we used suture ligation and bipolar diathermy. RESULTS: The
      rate of bleeding requiring second surgery for haemostasis was 3.6% in 2003-2005
      but only 2.0% in 2007-2009 (absolute risk reduction 1.6% (95% CI 0.22%-2.45%, p =
      0.04)). The median surgery time-including adenoidectomy and paracentesis surgery
      increased from 25 to 31 minutes (p<0.01). CONCLUSIONS: We have been able to
      substantiate that suturing of the faucial pillars nearly halves the rate of
      postoperative haemorrhage. Surgery takes 8 minutes longer on average. Bleeding
      occurs later, mostly after 24 h. The limitations of this study relate to its
      retrospective character and all the potential biases related to observational
      studies.

PMID- 23118901
TI  - Mushroom Ganoderma lucidum prevents colitis-associated carcinogenesis in mice.
AB  - BACKGROUND: Epidemiological studies suggest that mushroom intake is inversely
      correlated with gastric, gastrointestinal and breast cancers. We have recently
      demonstrated anticancer and anti-inflammatory activity of triterpene extract
      isolated from mushroom Ganoderma lucidum (GLT). The aim of the present study was
      to evaluate whether GLT prevents colitis-associated carcinogenesis in mice.
      METHODS/PRINCIPAL FINDINGS: Colon carcinogenesis was induced by the food-borne
      carcinogen (2-Amino-1-methyl-6-phenylimidazol[4,5-b]pyridine [PhIP]) and
      inflammation (dextran sodium sulfate [DSS]) in mice. Mice were treated with 0,
      100, 300 and 500 mg GLT/kg of body weight 3 times per week for 4 months. Cell
      proliferation, expression of cyclin D1 and COX-2 and macrophage infiltration was
      assessed by immunohistochemistry. The effect of GLT on XRE/AhR, PXR and rPXR was
      evaluated by the reporter gene assays. Expression of metabolizing enzymes CYP1A2,
      CYP3A1 and CYP3A4 in colon tissue was determined by immunohistochemistry. GLT
      treatment significantly suppressed focal hyperplasia, aberrant crypt foci (ACF)
      formation and tumor formation in mice exposed to PhIP/DSS. The anti-proliferative
      effects of GLT were further confirmed by the decreased staining with Ki-67 in
      colon tissues. PhIP/DSS-induced colon inflammation was demonstrated by the
      significant shortening of the large intestine and macrophage infiltrations,
      whereas GLT treatment prevented the shortening of colon lengths, and reduced
      infiltration of macrophages in colon tissue. GLT treatment also significantly
      down-regulated PhIP/DSS-dependent expression of cyclin D1, COX-2, CYP1A2 and
      CYP3A4 in colon tissue. CONCLUSIONS: Our data suggest that GLT could be
      considered as an alternative dietary approach for the prevention of colitis
      associated cancer.

PMID- 23118903
TI  - Astragalus root and elderberry fruit extracts enhance the IFN-beta stimulatory
      effects of Lactobacillus acidophilus in murine-derived dendritic cells.
AB  - Many foods and food components boost the immune system, but little data are
      available regarding the mechanisms by which they do. Bacterial strains have
      disparate effects in stimulating the immune system. In dendritic cells, the gram
      negative bacteria Escherichia coli upregulates proinflammatory cytokines, whereas
      gram-positive Lactobacillus acidophilus induces a robust interferon (IFN)-beta
      response. The immune-modulating effects of astragalus root and elderberry fruit
      extracts were examined in bone marrow-derived murine dendritic cells that were
      stimulated with L. acidophilus or E. coli. IFN-beta and other cytokines were
      measured by ELISA and RT-PCR. Endocytosis of fluorescence-labeled dextran and L.
      acidophilus in the presence of elderberry fruit or astragalus root extract was
      evaluated in dendritic cells. Our results show that both extracts enhanced L.
      acidophilus-induced IFN-beta production and slightly decreased the
      proinflammatory response to E. coli. The enhanced IFN-beta production was
      associated with upregulation of toll-like receptor 3 and to a varying degree, the
      cytokines IL-12, IL-6, IL-1beta and TNF-alpha. Both extracts increased
      endocytosis in immature dendritic cells, and only slightly influenced the
      viability of the cells. In conclusion, astragalus root and elderberry fruit
      extracts increase the IFN-beta inducing activity of L. acidophilus in dendritic
      cells, suggesting that they may exert antiviral and immune-enhancing activity.

PMID- 23118904
TI  - Urban tree species show the same hydraulic response to vapor pressure deficit
      across varying tree size and environmental conditions.
AB  - BACKGROUND: The functional convergence of tree transpiration has rarely been
      tested for tree species growing under urban conditions even though it is of
      significance to elucidate the relationship between functional convergence and
      species differences of urban trees for establishing sustainable urban forests in
      the context of forest water relations. METHODOLOGY/PRINCIPAL FINDINGS: We
      measured sap flux of four urban tree species including Cedrus deodara, Zelkova
      schneideriana, Euonymus bungeanus and Metasequoia glyptostroboides in an urban
      park by using thermal dissipation probes (TDP). The concurrent microclimate
      conditions and soil moisture content were also measured. Our objectives were to
      examine 1) the influence of tree species and size on transpiration, and 2) the
      hydraulic control of urban trees under different environmental conditions over
      the transpiration in response to VPD as represented by canopy conductance. The
      results showed that the functional convergence between tree diameter at breast
      height (DBH) and tree canopy transpiration amount (E(c)) was not reliable to
      predict stand transpiration and there were species differences within same DBH
      class. Species differed in transpiration patterns to seasonal weather progression
      and soil water stress as a result of varied sensitivity to water availability.
      Species differences were also found in their potential maximum transpiration rate
      and reaction to light. However, a same theoretical hydraulic relationship between
      G(c) at VPD = 1 kPa (G(cref)) and the G(c) sensitivity to VPD (-dG(c)/dlnVPD)
      across studied species as well as under contrasting soil water and R(s)
      conditions in the urban area. CONCLUSIONS/SIGNIFICANCE: We concluded that urban
      trees show the same hydraulic regulation over response to VPD across varying tree
      size and environmental conditions and thus tree transpiration could be predicted
      with appropriate assessment of G(cref).

PMID- 23118905
TI  - Prevalence of overweight, obesity, and abdominal obesity in a representative
      sample of Portuguese adults.
AB  - This study determined the prevalence of overweight, obesity, and abdominal
      obesity in the Portuguese adults and examined the relationship between above
      mentioned prevalences and educational level. Body mass, stature, and waist
      circumference were measured in a representative sample of the Portuguese
      population aged 18-103 years (n = 9,447; 18-64 years: n = 6,908; >= 65 years: n =
      2,539). Overweight and obesity corresponded to a body mass index ranging between
      25-29.9 kg/m(2) and >= 30 kg/m(2), respectively. Abdominal obesity was assessed
      as >102 cm for males and >88 cm for females. After adjusting for educational
      level, the combined prevalences of overweight and obesity were 66.6% in males and
      57.9% in females (18-64 years). Respective values in older adults (>= 65 years)
      were 70.4% for males and 74.7% for females. About 19.3% of adult males and 37.9%
      of adult females presented abdominal obesity. Correspondent values in older
      adults were 32.1%, for males, and 69.7%, for females. In adults, low educational
      level was related to an increased risk for overweight (OR = 2.54; 95% CI: 2.08
      3.09), obesity (OR = 2.76; 95% CI: 2.20-3.45), and abdominal obesity (OR = 5.48;
      95% CI: 4.60-6.52). This reinforces the importance of adjusting public health
      strategies for educational level.

PMID- 23118906
TI  - Does childhood diarrhea influence cognition beyond the diarrhea-stunting pathway?
AB  - BACKGROUND: Diarrhea is a leading cause of morbidity among children under 5 years
      of age in low- and middle-income countries yet the additional effects and
      sequelae, such as cognitive impairment associated with diarrhea, have not been
      quantified. METHODS: We quantified the association between diarrhea prevalence
      and cognitive outcomes while controlling for linear growth in 4 study
      populations. Cognition was assessed using different methods across sites and was
      expressed in standardized units. We built linear regression models for each study
      with standardized cognitive score as the outcome and diarrhea prevalence as the
      main predictor variable. We then conducted meta-analyses of the regression
      coefficients to generate pooled estimates of the association between diarrhea
      prevalence and cognition whilst controlling for anthropometric status and other
      covariates. RESULTS: Diarrhea was not a significant predictor of cognitive score
      in any site in the regression models or in the meta-analyses (Coefficient = 0.07;
      95% CI: -0.1, 0.2). The length for age Z- score was negatively related to
      cognition in all sites (0.18; 95% CI: 0.14, 0.21), with coefficients remarkably
      similar across sites (Coefficient Range: 0.168-0.186). CONCLUSIONS: We did not
      demonstrate an association between diarrhea and cognition with stunting included
      in the model. The links between diarrhea, stunting, and cognition provide
      additional rationale for accelerating interventions to reduce diarrhea.

PMID- 23118907
TI  - Plasmodium falciparum field isolates from South America use an atypical red blood
      cell invasion pathway associated with invasion ligand polymorphisms.
AB  - Studies of Plasmodium falciparum invasion pathways in field isolates have been
      limited. Red blood cell (RBC) invasion is a complex process involving two
      invasion protein families; Erythrocyte Binding-Like (EBL) and the Reticulocyte
      Binding-Like (PfRh) proteins, which are polymorphic and not fully characterized
      in field isolates. To determine the various P. falciparum invasion pathways used
      by parasite isolates from South America, we studied the invasion phenotypes in
      three regions: Colombia, Peru and Brazil. Additionally, polymorphisms in three
      members of the EBL (EBA-181, EBA-175 and EBL-1) and five members of the PfRh
      (PfRh1, PfRh2a, PfRh2b, PfRh4, PfRh5) families were determined. We found that
      most P. falciparum field isolates from Colombia and Peru invade RBCs through an
      atypical invasion pathway phenotypically characterized as resistant to all enzyme
      treatments (NrTrCr). Moreover, the invasion pathways and the ligand polymorphisms
      differed substantially among the Colombian and Brazilian isolates while the
      Peruvian isolates represent an amalgam of those present in the Colombian and
      Brazilian field isolates. The NrTrCr invasion profile was associated with the
      presence of the PfRh2a pepC variant, the PfRh5 variant 1 and EBA-181 RVNKN
      variant. The ebl and Pfrh expression levels in a field isolate displaying the
      NrTrCr profile also pointed to PfRh2a, PfRh5 and EBA-181 as being possibly the
      major players in this invasion pathway. Notably, our studies demonstrate the
      uniqueness of the Peruvian P. falciparum field isolates in terms of their
      invasion profiles and ligand polymorphisms, and present a unique opportunity for
      studying the ability of P. falciparum parasites to expand their invasion
      repertoire after being reintroduced to human populations. The present study is
      directly relevant to asexual blood stage vaccine design focused on invasion
      pathway proteins, suggesting that regional invasion variants and global
      geographical variation are likely to preclude a simple one size fits all type of
      vaccine.

PMID- 23118908
TI  - N300 and social affordances: a study with a real person and a dummy as stimuli.
AB  - Pictures of objects have been shown to automatically activate affordances, that
      is, actions that could be performed with the object. Similarly, pictures of faces
      are likely to activate social affordances, that is, interactions that would be
      possible with the person whose face is being presented. Most interestingly, if it
      is the face of a real person that is shown, one particular type of social
      interactions can even be carried out while event-related potentials (ERPs) are
      recorded. Indeed, subtle eye movements can be made to achieve an eye contact with
      the person with minimal artefacts on the EEG. The present study thus used the
      face of a real person to explore the electrophysiological correlates of
      affordances in a situation where some of them (i.e., eye contacts) are actually
      performed. The ERPs this person elicited were compared to those evoked by another
      3D stimulus: a real dummy, and thus by a stimulus that should also automatically
      activate eye contact affordances but with which such affordances could then be
      inhibited since they cannot be carried out with an object. The photos of the
      person and of the dummy were used as matching stimuli that should not activate
      social affordances as strongly as the two 3D stimuli and for which social
      affordances cannot be carried out. The fronto-central N300s to the real dummy
      were found of greater amplitudes than those to the photos and to the real person.
      We propose that these greater N300s index the greater inhibition needed after the
      stronger activations of affordances induced by this 3D stimulus than by the
      photos. Such an inhibition would not have occurred in the case of the real person
      because eye contacts were carried out.

PMID- 23118909
TI  - Differences between spinocerebellar ataxias and multiple system atrophy
      cerebellar type on proton magnetic resonance spectroscopy.
AB  - PURPOSE: A broad spectrum of diseases can manifest cerebellar ataxia. In this
      study, we investigated whether proton magnetic resonance spectroscopy (MRS) may
      help differentiate spinocerebellar ataxias (SCA) from multiple systemic atrophy-
      cerebellar type (MSA-C). MATERIAL AND METHODS: This prospective study recruited
      156 patients with ataxia, including spinocerebellar ataxia (SCA) types 1, 2, 3, 6
      and 17 (N = 94) and MSA-C (N = 62), and 44 healthy controls. Single voxel proton
      MRS in the cerebellar hemispheres and vermis were measured. The differences were
      evaluated using nonparametric statistic tests. RESULTS: When compared with
      healthy controls, the cerebellar and vermis NAA/Cr and NAA/Cho were lower in all
      patients(p<0.002). The Cho/Cr was lower in SCA2 and MSA-C (p<0.0005). The NAA/Cr
      and Cho/Cr were lower in MSA-C or SCA2 comparing with SCA3 or SCA6. The MRS
      features of SCA1 were in between (p<0.018). The cerebellar NAA/Cho was lower in
      SCA2 than SCA1, SCA3 or SCA6 (p<0.04). The cerebellar NAA/Cho in MSA-C was lower
      than SCA3 (p<0.0005). In the early stages of diseases (SARA score<10),
      significant lower NAA/Cr and NAA/Cho in SCA2, SCA3, SCA6 or MSA-C were observed
      comparing with healthy controls (p<0.017). The Cho/Cr was lower in MSA-C or SCA2
      (p<0.0005). Patients with MSA-C and SCA2 had lower NAA/Cr and Cho/Cr than SCA3 or
      SCA6 (p<0.016). CONCLUSION: By using MRS, significantly lower NAA/Cr, Cho/Cr and
      NAA/Cho in the cerebellar hemispheres and vermis were found in patients with
      ataxia (SCAs and MSA-C). Rapid neuronal degeneration and impairment of membrane
      activities were observed more often in patients with MSA-C than those with SCA,
      even in early stages. MRS could also help distinguish between SCA2 and other
      subtypes of SCAs. MRS ratios may be of use as biomarkers in early stages of
      disease and should be further assessed in a longitudinal study.

PMID- 23118910
TI  - A clinical prediction score in addition to WHO criteria for anti-retroviral
      treatment failure in resource-limited settings--experience from Lesotho.
AB  - OBJECTIVE: To assess the positive predictive value (PPV) of a clinical score for
      viral failure among patients fulfilling the WHO-criteria for anti-retroviral
      treatment (ART) failure in rural Lesotho. METHODS: Patients fulfilling clinical
      and/or immunological WHO failure-criteria were enrolled. The score includes the
      following predictors: Prior ART exposure (1 point), CD4-count below baseline (1),
      25% and 50% drop from peak CD4-count (1 and 2), hemoglobin drop>=1 g/dL (1), CD4
      count<100/ul after 12 months (1), new onset papular pruritic eruption (1), and
      adherence<95% (3). A nurse assessed the score the day blood was drawn for viral
      load (VL). Reported confidence intervals (CI) were calculated using Wilsons
      method. RESULTS: Among 1'131 patients on ART >= 6 months, 134 (11.8%) had
      immunological and/or clinical failure, 104 (78%) had blood drawn (13 died, 10
      lost to follow-up, 7 did not show up). From 92 (88%) a result could be obtained
      (2 samples hemolysed, 10 lost). Out of these 92 patients 47 (51%) had viral
      failure (>= 5000 copies), 27 (29%) viral suppression (<40) and 18 (20%)
      intermediate viremia (40-4999). Overall, 20 (22%) had a score >= 5. A score >= 5
      had a PPV of 100% to detect a VL>40 copies (95%CI: 84-100), and of 90% to detect
      a VL >= 5000 copies (70-97). Within the score, adherence<95%, CD4-count<100/ul
      and papular pruritic eruption were the strongest single predictors. Among 47
      patients failing, 8 (17%) died before or within 4 weeks after being switched.
      Overall mortality was 4 (20%) among those with score >= 5 and 4 (5%) if score<5
      (OR 4.3; 95%CI: 0.96-18.84, p = 0.057). CONCLUSION: A score >= 5 among patients
      fulfilling WHO-criteria had a PPV of 100% for a detectable VL and 90% for viral
      failure. In settings without regular access to VL-testing, this PPV may be
      considered high enough to switch this patient-group to second-line treatment
      without confirmatory VL-test.

PMID- 23118911
TI  - Hemoglobin A1c and arterial and ventricular stiffness in older adults.
AB  - OBJECTIVE: Arterial and ventricular stiffening are characteristics of diabetes
      and aging which confer significant morbidity and mortality; advanced glycation
      endproducts (AGE) are implicated in this stiffening pathophysiology. We examined
      the association between HbA(1c), an AGE, with arterial and ventricular stiffness
      measures in older individuals without diabetes. RESEARCH DESIGN & METHODS:
      Baseline HbA(1c) was measured in 830 participants free of diabetes defined by
      fasting glucose or medication use in the Cardiovascular Health Study, a
      population-based cohort study of adults aged >= 65 years. We performed cross
      sectional analyses using baseline exam data including echocardiography, ankle and
      brachial blood pressure measurement, and carotid ultrasonography. We examined the
      adjusted associations between HbA(1c) and multiple arterial and ventricular
      stiffness measures by linear regression models and compared these results to the
      association of fasting glucose (FG) with like measures. RESULTS: HbA(1c) was
      correlated with fasting and 2-hour postload glucose levels (r = 0.21; p<0.001 for
      both) and positively associated with greater body-mass index and black race. In
      adjusted models, HbA(1c) was not associated with any measure of arterial or
      ventricular stiffness, including pulse pressure (PP), carotid intima-media
      thickness, ankle-brachial index, end-arterial elastance, or left ventricular mass
      (LVM). FG levels were positively associated with systolic, diastolic and PP and
      LVM. CONCLUSIONS: In this sample of older adults without diabetes, HbA(1c) was
      not associated with arterial or ventricular stiffness measures, whereas FG levels
      were. The role of AGE in arterial and ventricular stiffness in older adults may
      be better assessed using alternate AGE markers.

PMID- 23118912
TI  - A robust method of measuring other-race and other-ethnicity effects: the
      Cambridge Face Memory Test format.
AB  - Other-race and other-ethnicity effects on face memory have remained a topic of
      consistent research interest over several decades, across fields including face
      perception, social psychology, and forensic psychology (eyewitness testimony).
      Here we demonstrate that the Cambridge Face Memory Test format provides a robust
      method for measuring these effects. Testing the Cambridge Face Memory Test
      original version (CFMT-original; European-ancestry faces from Boston USA) and a
      new Cambridge Face Memory Test Chinese (CFMT-Chinese), with European and Asian
      observers, we report a race-of-face by race-of-observer interaction that was
      highly significant despite modest sample size and despite observers who had quite
      high exposure to the other race. We attribute this to high statistical power
      arising from the very high internal reliability of the tasks. This power also
      allows us to demonstrate a much smaller within-race other ethnicity effect, based
      on differences in European physiognomy between Boston faces/observers and
      Australian faces/observers (using the CFMT-Australian).

PMID- 23118913
TI  - FREQ-Seq: a rapid, cost-effective, sequencing-based method to determine allele
      frequencies directly from mixed populations.
AB  - Understanding evolutionary dynamics within microbial populations requires the
      ability to accurately follow allele frequencies through time. Here we present a
      rapid, cost-effective method (FREQ-Seq) that leverages Illumina next-generation
      sequencing for localized, quantitative allele frequency detection. Analogous to
      RNA-Seq, FREQ-Seq relies upon counts from the >10(5) reads generated per locus
      per time-point to determine allele frequencies. Loci of interest are directly
      amplified from a mixed population via two rounds of PCR using inexpensive, user
      designed oligonucleotides and a bar-coded bridging primer system that can be
      regenerated in-house. The resulting bar-coded PCR products contain the adapters
      needed for Illumina sequencing, eliminating further library preparation. We
      demonstrate the utility of FREQ-Seq by determining the order and dynamics of
      beneficial alleles that arose as a microbial population, founded with an
      engineered strain of Methylobacterium, evolved to grow on methanol. Quantifying
      allele frequencies with minimal bias down to 1% abundance allowed effective
      analysis of SNPs, small in-dels and insertions of transposable elements. Our data
      reveal large-scale clonal interference during the early stages of adaptation and
      illustrate the utility of FREQ-Seq as a cost-effective tool for tracking allele
      frequencies in populations.

PMID- 23118914
TI  - The response of dark septate endophytes (DSE) to heavy metals in pure culture.
AB  - Dark septate endophytes (DSE) occur widely in association with plants exposed to
      heavy metal stress. However, little is known about the response of DSE exposed to
      heavy metals. In this study, five DSE were isolated from the roots of Astragalus
      adsurgens Pall. seedlings growing on lead-zinc mine tailings in China. Based on
      morphological characteristics and DNA sequence analyses, the isolates were
      identified as Gaeumannomyces cylindrosporus, Paraphoma chrysanthemicola,
      Phialophora mustea, Exophiala salmonis, and Cladosporium cladosporioides. G.
      cylindrosporus was selected to explore responses to Pb stress. Scanning electron
      microscopic observations of G. cylindrosporus grown on solid medium revealed
      curling of hyphae and formation of hyphal coils in response to Pb. In contrast,
      in liquid medium, hyphae became thick and swollen with an increase in Pb (II)
      concentration. We interpret that these changes are related to the variation in
      cell wall components. We also demonstrated that fungal melanin content increased
      with the addition of Pb(II). Melanin, as an important component in the cell wall,
      is known to be an essential antioxidant responsible for decreasing heavy metal
      toxicity. We also measured the total soluble protein content and glutathione
      (GSH) concentrations in G. cylindrosporus and found that they initially increased
      and then decreased with the increase of Pb(II) concentrations. The antioxidant
      enzyme activities were also examined, and the results showed that superoxide
      dismutase (SOD) activity was significantly positively correlated with Pb(II)
      concentrations (r = 0.957, P<0.001). Collectively, our observations indicate that
      the intracellular antioxidant systems, especially fungal melanin, play an
      important role in abating the hazards of heavy metals.

PMID- 23118915
TI  - Stress activated protein kinase pathway modulates homologous recombination in
      fission yeast.
AB  - Rad52 is a key player in homologous recombination (HR), a DNA repair pathway that
      is dedicated to double strand breaks repair and recovery of perturbed replication
      forks. Here we show that fission yeast Rad52 homologue is phosphorylated when S
      phase cells are exposed to ROS inducers such as ultraviolet A radiation or
      hydrogen peroxide, but not to ultraviolet C or camptothecin. Phosphorylation does
      not depend on kinases Chk1, Rad3, Tel1 or Cdc2, but depends on a functional
      stress activated protein kinase (SAPK) pathway and can be partially prevented by
      anti-oxidant treatment. Indeed, cells lacking Sty1, the major fission yeast MAP
      kinase of the SAPK pathway, do not display Rad52 phosphorylation and have UVA
      induced Rad52 foci that persist longer if compared to wild type cells. In
      addition, spontaneous intrachromosomal HR is diminished in cells lacking Sty1
      and, more precisely, gene conversion is affected. Moreover, HR induced by site
      specific arrest of replication forks is twice less efficient in cells that do not
      express Sty1. Importantly, impairing HR by deletion of the gene encoding the
      recombinase Rhp51 leads to Sty1 dependent Rad52 phosphorylation. Thus, SAPK
      pathway impinges on early step of HR through phosphorylation of Rad52 in cells
      challenged by oxidative stress or lacking Rhp51 and is required to promote
      spontaneous gene conversion and recovery from blocked replication forks.

PMID- 23118916
TI  - Genome-wide scan identifies variant in TNFSF13 associated with serum IgM in a
      healthy Chinese male population.
AB  - IgM provides a first line of defense during microbial infections. Serum IgM
      levels are detected routinely in clinical practice. And IgM is a genetically
      complex trait. We conducted a two-stage genome-wide association study (GWAS) to
      identify genetic variants affecting serum IgM levels in a Chinese population of
      3495, including 1999 unrelated subjects in the first stage and 1496 independent
      individuals in the second stage. Our data show that a common single nucleotide
      polymorphism (SNP), rs11552708 located in the TNFSF13 gene was significantly
      associated with IgM levels (p = 5.00*10(-7) in first stage, p = 1.34*10(-3) in
      second stage, and p = 4.22*10(-9) when combined). Besides, smoking was identified
      to be associated with IgM levels in both stages (P<0.05), but there was no
      significant interaction between smoking and the identified SNP (P>0.05). It is
      suggested that TNFSF13 may be a susceptibility gene affecting serum IgM levels in
      Chinese male population.

PMID- 23118917
TI  - Vitamin k intake and plasma desphospho-uncarboxylated matrix Gla-protein levels
      in kidney transplant recipients.
AB  - Vitamin K is essential for activation of gamma-carboxyglutamate (Gla)-proteins
      including the vascular calcification inhibitor matrix Gla-protein (MGP).
      Insufficient vitamin K intake leads to production of uncarboxylated, mostly
      inactive proteins and contributes to an increased cardiovascular risk. In kidney
      transplant recipients, cardiovascular risk is high but vitamin K intake and
      status have not been defined. We investigated dietary vitamin K intake, vascular
      vitamin K status and its determinants in kidney transplant recipients. We
      estimated vitamin K intake in a cohort of kidney transplant recipients (n = 60)
      with stable renal function (creatinine clearance 61 [42-77] (median
      [interquartile range]) ml/min), who were 75 [35-188] months after
      transplantation, using three-day food records and food frequency questionnaires.
      Vascular vitamin K status was assessed by measuring plasma desphospho
      uncarboxylated MGP (dp-ucMGP). Total vitamin K intake was below the recommended
      level in 50% of patients. Lower vitamin K intake was associated with less
      consumption of green vegetables (33 vs 40 g/d, p = 0.06) and increased dp-ucMGP
      levels (621 vs 852 pmol/L, p<0.05). Accordingly, dp-ucMGP levels were elevated
      (>500 pmol/L) in 80% of patients. Multivariate regression identified creatinine
      clearance, coumarin use, body mass index, high sensitivity-CRP and sodium
      excretion as independent determinants of dp-ucMGP levels. In a considerable part
      of the kidney transplant population, vitamin K intake is too low for maximal
      carboxylation of vascular MGP. The high dp-ucMGP levels may result in an
      increased risk for arterial calcification. Whether increasing vitamin K intake
      may have health benefits for kidney transplant recipients should be addressed by
      future studies.

PMID- 23118918
TI  - A new mouse model for the study of human breast cancer metastasis.
AB  - Breast cancer is the most common cancer in women, and this prevalence has a major
      impact on health worldwide. Localized breast cancer has an excellent prognosis,
      with a 5-year relative survival rate of 85%. However, the survival rate drops to
      only 23% for women with distant metastases. To date, the study of breast cancer
      metastasis has been hampered by a lack of reliable metastatic models. Here we
      describe a novel in vivo model using human breast cancer xenografts in NOD scid
      gamma (NSG) mice; in this model human breast cancer cells reliably metastasize to
      distant organs from primary tumors grown within the mammary fat pad. This model
      enables the study of the entire metastatic process from the proper anatomical
      site, providing an important new approach to examine the mechanisms underlying
      breast cancer metastasis. We used this model to identify gene expression changes
      that occur at metastatic sites relative to the primary mammary fat pad tumor. By
      comparing multiple metastatic sites and independent cell lines, we have
      identified several gene expression changes that may be important for tumor growth
      at distant sites.

PMID- 23118919
TI  - A cross-sectional study of individuals seeking information on transient ischemic
      attack and stroke symptoms online: a target for intervention?
AB  - BACKGROUND: Individuals with TIA/stroke symptoms often do not seek urgent medical
      attention. We assessed the feasibility of identifying individuals searching for
      information on TIA/stroke symptoms online as a target for future interventions to
      encourage urgent evaluation and we evaluated the performance of a self-reported
      risk score to identify subjects with true TIA or stroke. METHODOLOGY/PRINCIPAL
      FINDINGS: We placed online advertisements to target English-speaking adults in
      the United States searching for TIA/stroke-related keywords. After completing an
      online questionnaire, participants were telephoned by a vascular neurologist to
      assess the likelihood of TIA/stroke. We used logistic regression and the c
      statistic to assess associations and model discrimination respectively. Over 122
      days, 251 (1%) of 25,292 website visitors completed the online questionnaire and
      175 were reached by telephone (mean age 58.5 years; 63% women) for follow-up. Of
      these participants, 37 (21%) had symptoms within 24 hours, 60 (34%) had not had a
      medical evaluation yet, and 68 (39%) had TIA/stroke. Applying a modified ABCD(2)
      score yielded a c-statistic of 0.66, but 2 of 12 with a zero score had a
      TIA/stroke. Those with new symptoms were more likely to have TIA/stroke (OR 4.90,
      95% CI 2.56-9.09). CONCLUSIONS/SIGNIFICANCE: Individuals with TIA/stroke that are
      seeking real-time information on symptoms online can be readily identified, in
      some cases before they have sought formal medical evaluation. Although a simple
      self-reported risk score was unable to identify a low-risk population in this
      selected group, this population may still present an attractive target for future
      interventions designed to encourage urgent medical evaluation.

PMID- 23118920
TI  - Forkhead box protein A2 (FOXA2) protein stability and activity are regulated by
      sumoylation.
AB  - The forkhead box protein A2 (FOXA2) is an important regulator of glucose and
      lipid metabolism and organismal energy balance. Little is known about how FOXA2
      protein expression and activity are regulated by post-translational
      modifications. We have identified that FOXA2 is post-translationally modified by
      covalent attachment of a small ubiquitin related modifier-1 (SUMO-1) and mapped
      the sumoylation site to the amino acid lysine 6 (K6). Preventing sumoylation by
      mutating the SUMO acceptor K6 to arginine resulted in downregulation of FOXA2
      protein but not RNA expression in INS-1E insulinoma cells. K6R mutation also
      downregulated FOXA2 protein levels in HepG2 hepatocellular carcinoma cells,
      HCT116 colon cancer cells and LNCaP and DU145 prostate cancer cells. Further,
      interfering with FOXA2 sumoylation through siRNA mediated knockdown of UBC9, an
      essential SUMO E2 conjugase, resulted in downregulation of FOXA2 protein levels.
      Stability of sumoylation deficient FOXA2K6R mutant protein was restored when SUMO
      1 was fused in-frame. FOXA2 sumoylation and FOXA2 protein levels were increased
      by PIAS1 SUMO ligase but not a SUMO ligase activity deficient PIAS1 mutant.
      Although expressed at lower levels, sumoylation deficient FOXA2K6R mutant protein
      was detectable in the nucleus indicating that FOXA2 nuclear localization is
      independent of sumoylation. Sumoylation increased the transcriptional activity of
      FOXA2 on Pdx-1 area I enhancer. Together, our results show that sumoylation
      regulates FOXA2 protein expression and activity.

PMID- 23118921
TI  - The guanine nucleotide exchange factor RIC8 regulates conidial germination
      through Galpha proteins in Neurospora crassa.
AB  - Heterotrimeric G protein signaling is essential for normal hyphal growth in the
      filamentous fungus Neurospora crassa. We have previously demonstrated that the
      non-receptor guanine nucleotide exchange factor RIC8 acts upstream of the Galpha
      proteins GNA-1 and GNA-3 to regulate hyphal extension. Here we demonstrate that
      regulation of hyphal extension results at least in part, from an important role
      in control of asexual spore (conidia) germination. Loss of GNA-3 leads to a
      drastic reduction in conidial germination, which is exacerbated in the absence of
      GNA-1. Mutation of RIC8 leads to a reduction in germination similar to that in
      the Deltagna-1, Deltagna-3 double mutant, suggesting that RIC8 regulates conidial
      germination through both GNA-1 and GNA-3. Support for a more significant role for
      GNA-3 is indicated by the observation that expression of a GTPase-deficient,
      constitutively active gna-3 allele in the Deltaric8 mutant leads to a significant
      increase in conidial germination. Localization of the three Galpha proteins
      during conidial germination was probed through analysis of cells expressing
      fluorescently tagged proteins. Functional TagRFP fusions of each of the three
      Galpha subunits were constructed through insertion of TagRFP in a conserved loop
      region of the Galpha subunits. The results demonstrated that GNA-1 localizes to
      the plasma membrane and vacuoles, and also to septa throughout conidial
      germination. GNA-2 and GNA-3 localize to both the plasma membrane and vacuoles
      during early germination, but are then found in intracellular vacuoles later
      during hyphal outgrowth.

PMID- 23118922
TI  - The biological origin of linguistic diversity.
AB  - In contrast with animal communication systems, diversity is characteristic of
      almost every aspect of human language. Languages variously employ tones, clicks,
      or manual signs to signal differences in meaning; some languages lack the noun
      verb distinction (e.g., Straits Salish), whereas others have a proliferation of
      fine-grained syntactic categories (e.g., Tzeltal); and some languages do without
      morphology (e.g., Mandarin), while others pack a whole sentence into a single
      word (e.g., Cayuga). A challenge for evolutionary biology is to reconcile the
      diversity of languages with the high degree of biological uniformity of their
      speakers. Here, we model processes of language change and geographical dispersion
      and find a consistent pressure for flexible learning, irrespective of the
      language being spoken. This pressure arises because flexible learners can best
      cope with the observed high rates of linguistic change associated with divergent
      cultural evolution following human migration. Thus, rather than genetic
      adaptations for specific aspects of language, such as recursion, the coevolution
      of genes and fast-changing linguistic structure provides the biological basis for
      linguistic diversity. Only biological adaptations for flexible learning combined
      with cultural evolution can explain how each child has the potential to learn any
      human language.

PMID- 23118923
TI  - Respiratory syncytial virus inhibits ciliagenesis in differentiated normal human
      bronchial epithelial cells: effectiveness of N-acetylcysteine.
AB  - Persistent respiratory syncytial virus (RSV) infections have been associated with
      the exacerbation of chronic inflammatory diseases, including chronic obstructive
      pulmonary disease (COPD). This virus infects the respiratory epithelium, leading
      to chronic inflammation, and induces the release of mucins and the loss of cilia
      activity, two factors that determine mucus clearance and the increase in sputum
      volume. These alterations involve reactive oxygen species-dependent mechanisms.
      The antioxidant N-acetylcysteine (NAC) has proven useful in the management of
      COPD, reducing symptoms, exacerbations, and accelerated lung function decline.
      NAC inhibits RSV infection and mucin release in human A549 cells. The main
      objective of this study was to analyze the effects of NAC in modulating ciliary
      activity, ciliagenesis, and metaplasia in primary normal human bronchial
      epithelial cell (NHBEC) cultures infected with RSV. Our results indicated that
      RSV induced ultrastructural abnormalities in axonemal basal bodies and decreased
      the expression of beta-tubulin as well as two genes involved in ciliagenesis,
      FOXJ1 and DNAI2. These alterations led to a decrease in ciliary activity.
      Furthermore, RSV induced metaplastic changes to the epithelium and increased the
      number of goblet cells and the expression of MUC5AC and GOB5. NAC restored the
      normal functions of the epithelium, inhibiting ICAM1 expression, subsequent RSV
      infection through mechanisms involving nuclear receptor factor 2, and the
      expression of heme oxygenase 1, which correlated with the restoration of the
      antioxidant capacity, the intracellular H(2)O(2) levels and glutathione content
      of NHBECs. The results presented in this study support the therapeutic use of NAC
      for the management of chronic respiratory diseases, including COPD.

PMID- 23118924
TI  - Fragmentation of SIV-gag vaccine induces broader T cell responses.
AB  - BACKGROUND: High mutation rates of human immunodeficiency virus (HIV) allows
      escape from T cell recognition preventing development of effective T cell
      vaccines. Vaccines that induce diverse T cell immune responses would help
      overcome this problem. Using SIV gag as a model vaccine, we investigated two
      approaches to increase the breadth of the CD8 T cell response. Namely, fusion of
      vaccine genes to ubiquitin to target the proteasome and increase levels of MHC
      class I peptide complexes and gene fragmentation to overcome competition between
      epitopes for presentation and recognition. METHODOLOGY/PRINCIPAL FINDINGS: three
      vaccines were compared: full-length unmodified SIV-mac239 gag, full-length gag
      fused at the N-terminus to ubiquitin and 7 gag fragments of equal size spanning
      the whole of gag with ubiquitin-fused to the N-terminus of each fragment. Genes
      were cloned into a replication defective adenovirus vector and immunogenicity
      assessed in an in vitro human priming system. The breadth of the CD8 T cell
      response, defined by the number of distinct epitopes, was assessed by IFN-gamma
      ELISPOT and memory phenotype and cytokine production evaluated by flow cytometry.
      We observed an increase of two- to six-fold in the number of epitopes recognised
      in the ubiquitin-fused fragments compared to the ubiquitin-fused full-length gag.
      In contrast, although proteasomal targeting was achieved, there was a marked
      reduction in the number of epitopes recognised in the ubiquitin-fused full-length
      gag compared to the full-length unmodified gene, but there were no differences in
      the number of epitope responses induced by non-ubiquitinated full-length gag and
      the ubiquitin-fused mini genes. Fragmentation and ubiquitination did not affect T
      cell memory differentiation and polyfunctionality, though most responses were
      directed against the Ad5 vector. CONCLUSION/SIGNIFICANCE: Fragmentation but not
      fusion with ubiquitin increases the breadth of the CD8 T vaccine response against
      SIV-mac239 gag. Thus gene fragmentation of HIV vaccines may maximise responses.

PMID- 23118925
TI  - DSIR: assessing the design of highly potent siRNA by testing a set of cancer
      relevant target genes.
AB  - Chemically synthesized small interfering RNA (siRNA) is a widespread molecular
      tool used to knock down genes in mammalian cells. However, designing potent siRNA
      remains challenging. Among tools predicting siRNA efficacy, very few have been
      validated on endogenous targets in realistic experimental conditions. We
      previously described a tool to assist efficient siRNA design (DSIR, Designer of
      siRNA), which focuses on intrinsic features of the siRNA sequence. Here, we
      evaluated DSIR's performance by systematically investigating the potency of the
      siRNA it designs to target ten cancer-related genes. mRNA knockdown was measured
      by quantitative RT-PCR in cell-based assays, revealing that over 60% of siRNA
      sequences designed by DSIR silenced their target genes by at least 70%. Silencing
      efficacy was sustained even when low siRNA concentrations were used. This
      systematic analysis revealed in particular that, for a subset of genes, the
      efficiency of siRNA constructs significantly increases when the sequence is
      located closer to the 5'-end of the target gene coding sequence, suggesting the
      distance to the 5'-end as a new feature for siRNA potency prediction. A new
      version of DSIR incorporating these new findings, as well as the list of
      validated siRNA against the tested cancer genes, has been made available on the
      web (http://biodev.extra.cea.fr/DSIR).

PMID- 23118927
TI  - Mental fatigue affects visual selective attention.
AB  - Mental fatigue is a form of fatigue, induced by continuous task performance.
      Mentally fatigued people often report having a hard time keeping their attention
      focussed and being easily distracted. In this study, we examined the relation
      between mental fatigue, as induced by time on task, and attention-related changes
      in event-related potentials (ERPs). EEG, reaction times and response accuracies
      were obtained from 17 healthy volunteers during two hours of task performance on
      an adapted Eriksen flanker task. In this task, the size of targets and flankers
      was manipulated to discern neuronal processes that are related to processing of
      relevant information from processes related to the processing of irrelevant
      information. The ERP data showed that effects induced by target size manipulation
      were not affected by time on task, while an initial effect of flanker size
      manipulation decreased gradually with increasing time on task. We conclude that
      attention was affected by mental fatigue, in the form of a decrease in the
      ability to suppress irrelevant information. In behavioural results, this was
      reflected by a tendency of participants to increasingly base their response
      decision on irrelevant information, resulting in decreased response accuracies.

PMID- 23118926
TI  - Everolimus and sirolimus in combination with cyclosporine have different effects
      on renal metabolism in the rat.
AB  - Enhancement of calcineurin inhibitor nephrotoxicity by sirolimus (SRL) is
      limiting the clinical use of this drug combination. We compared the dose
      dependent effects of the structurally related everolimus (EVL) and sirolimus
      (SRL) alone, and in combination with cyclosporine (CsA), on the rat kidney. Lewis
      rats were treated by oral gavage for 28 days using a checkerboard dosing format
      (0, 3.0, 6.0 and 10.0 CsA and 0, 0.5, 1.5 and 3.0 mg/kg/day SRL or EVL, n =
      4/dose combination). After 28 days, oxidative stress, energy charge, kidney
      histologies, glomerular filtration rates, and concentrations of the
      immunosuppressants were measured along with (1)H-magnetic resonance spectroscopy
      (MRS) and gas chromatography- mass spectrometry profiles of cellular metabolites
      in urine. The combination of CsA with SRL led to higher urinary glucose
      concentrations and decreased levels of urinary Krebs cycle metabolites when
      compared to controls, suggesting that CsA+SRL negatively impacted proximal tubule
      metabolism. Unsupervised principal component analysis of MRS spectra
      distinguished unique urine metabolite patterns of rats treated with CsA+SRL from
      those treated with CsA+EVL and the controls. SRL, but not EVL blood
      concentrations were inversely correlated with urine Krebs cycle metabolite
      concentrations. Interestingly, the higher the EVL concentration, the closer urine
      metabolite patterns resembled those of controls, while in contrast, the
      combination of the highest doses of CsA+SRL showed the most significant
      differences in metabolite patterns. Surprisingly in this rat model, EVL and SRL
      in combination with CsA had different effects on kidney biochemistry, suggesting
      that further exploration of EVL in combination with low dose calcineurin
      inhibitors may be of potential benefit.

PMID- 23118928
TI  - In vivo and in vitro suppression of hepatocellular carcinoma by EF24, a curcumin
      analog.
AB  - The synthetic compound 3,5-bis(2-flurobenzylidene)piperidin-4-one (EF24) is a
      potent analog of curcumin that exhibits enhanced biological activity and
      bioavailability without increasing toxicity. EF24 exerts antitumor activity by
      arresting the cell cycle and inducing apoptosis, suppressing many types of cancer
      cells in vitro. The antiproliferative and antiangiogenic properties of EF24
      provide theoretical support for its development and application to liver cancers.
      We investigated the in vitro and in vivo activities of EF24 on liver cancer to
      better understand its therapeutic effects and mechanisms. EF24 induced
      significant apoptosis and G2/M-phase cell cycle arrest in mouse liver cancer cell
      lines, Hepa1-6 and H22. The expression levels of G2/M cell cycle regulating
      factors, cyclin B1 and Cdc2, were significantly decreased, pp53, p53, and p21
      were significantly increased in EF24-treated cells. In addition, EF24 treatment
      significantly reduced Bcl-2 concomitant with an increase in Bax, enhanced the
      release of cytochrome c from the mitochondria into the cytosol, resulting in an
      upregulation of cleaved-caspase-3, which promoted poly (ADP-ribose) polymerase
      cleavage. EF24-treated cells also displayed decreases in phosphorylated Akt,
      phosphorylated extracellular signal-regulated kinase and vascular endothelial
      growth factor. Our in vitro protein expression data were confirmed in vivo using
      a subcutaneous hepatocellular carcinoma (HCC) tumor model. This mouse HCC model
      confirmed that total body weight was unchanged following EF24 treatment, although
      tumor weight was significantly decreased. Using an orthotopic HCC model, EF24
      significantly reduced the liver/body weight ratio and relative tumor areas
      compared to the control group. In situ detection of apoptotic cells and
      quantification of Ki-67, a biomarker of cell proliferation, all indicated
      significant tumor suppression with EF24 treatment. These results suggest that
      EF24 exhibits anti-tumor activity on liver cancer cells via mitochondria
      dependent apoptosis and inducing cell cycle arrest coupled with antiangiogenesis.
      The demonstrated activities of EF24 support its further evaluation as a treatment
      for human liver cancers.

PMID- 23118929
TI  - When math hurts: math anxiety predicts pain network activation in anticipation of
      doing math.
AB  - Math can be difficult, and for those with high levels of mathematics-anxiety
      (HMAs), math is associated with tension, apprehension, and fear. But what
      underlies the feelings of dread effected by math anxiety? Are HMAs' feelings
      about math merely psychological epiphenomena, or is their anxiety grounded in
      simulation of a concrete, visceral sensation - such as pain - about which they
      have every right to feel anxious? We show that, when anticipating an upcoming
      math-task, the higher one's math anxiety, the more one increases activity in
      regions associated with visceral threat detection, and often the experience of
      pain itself (bilateral dorso-posterior insula). Interestingly, this relation was
      not seen during math performance, suggesting that it is not that math itself
      hurts; rather, the anticipation of math is painful. Our data suggest that pain
      network activation underlies the intuition that simply anticipating a dreaded
      event can feel painful. These results may also provide a potential neural
      mechanism to explain why HMAs tend to avoid math and math-related situations,
      which in turn can bias HMAs away from taking math classes or even entire math
      related career paths.

PMID- 23118930
TI  - The submerged dyslexia iceberg: how many school children are not diagnosed?
      Results from an Italian study.
AB  - BACKGROUND: Although dyslexia is one of the most common neurobehavioral disorders
      affecting children, prevalence is uncertain and available data are scanty and
      dated. The objective of this study is to evaluate the prevalence of dyslexia in
      an unselected school population using clearly defined and rigorous diagnostic
      criteria and methods. METHODS: Cross sectional study. We selected a random
      cluster sample of 94 fourth grade elementary school classes of Friuli Venezia
      Giulia, a Region of North Eastern Italy. We carried out three consecutive levels
      of screening: the first two at school and the last at the Neuropsychiatry Unit of
      a third level Mother and Child Hospital. The main outcome measure was the
      prevalence of dyslexia, defined as the number of children positive to the third
      level of screening divided by the total number of children enrolled. RESULTS: We
      recruited 1774 children aged 8-10 years, of which 1528 received parents' consent
      to participate. After applying exclusion criteria, 1357 pupils constituted the
      final working sample. The prevalence of dyslexia in the enrolled population
      ranged from 3.1% (95% CI 2.2-4.1%) to 3.2% (95% CI 2.4-4.3%) depending on
      different criteria adopted. In two out of three children with dyslexia the
      disorder had not been previously diagnosed. CONCLUSIONS: This study shows that
      dyslexia is largely underestimated in Italy and underlines the need for reliable
      information on prevalence, in order to better allocate resources both to Health
      Services and Schools.

PMID- 23118931
TI  - Psychological stress on female mice diminishes the developmental potential of
      oocytes: a study using the predatory stress model.
AB  - Although the predatory stress experimental protocol is considered more
      psychological than the restraint protocol, it has rarely been used to study the
      effect of psychological stress on reproduction. Few studies exist on the direct
      effect of psychological stress to a female on developmental competence of her
      oocytes, and the direct effect of predatory maternal stress on oocytes has not
      been reported. In this study, a predatory stress system was first established for
      mice with cats as predators. Beginning 24 h after injection of equine chorionic
      gonadotropin, female mice were subjected to predatory stress for 24 h. Evaluation
      of mouse responses showed that the predatory stress system that we established
      increased anxiety-like behaviors and plasma cortisol concentrations significantly
      and continuously while not affecting food and water intake of the mice. In vitro
      experiments showed that whereas oocyte maturation and Sr(2+) activation or
      fertilization were unaffected by maternal predatory stress, rate of blastocyst
      formation and number of cells per blastocyst decreased significantly in stressed
      mice compared to non-stressed controls. In vivo embryo development indicated that
      both the number of blastocysts recovered per donor mouse and the average number
      of young per recipient after embryo transfer of blastocysts with similar cell
      counts were significantly lower in stressed than in unstressed donor mice. It is
      concluded that the predatory stress system we established was both effective and
      durative to induce mouse stress responses. Furthermore, predatory stress applied
      during the oocyte pre-maturation stage significantly impaired oocyte
      developmental potential while exerting no measurable impact on nuclear
      maturation, suggesting that cytoplasmic maturation of mouse oocytes was more
      vulnerable to maternal stress than nuclear maturation.

PMID- 23118932
TI  - Mitigation of oxidative damage by green tea polyphenols and Tai Chi exercise in
      postmenopausal women with osteopenia.
AB  - BACKGROUND: Osteoporosis is a degenerative bone disease predominantly in
      postmenopausal women. Green tea polyphenols (GTP) and Tai Chi (TC) have been
      shown to be beneficial on human bone health. This study examined the efficacy of
      GTP and TC on mitigation of oxidative damage in postmenopausal women with
      osteopenia. METHODS: A 6-month randomized and placebo-controlled clinical trial
      was conducted in 171 postmenopausal women with osteopenia, who were recruited
      from Lubbock County, Texas. These participants were treated with placebo, GTP
      (500 mg daily), placebo + TC (60-minute group exercise, 3 times/week), or GTP
      (500 mg daily) + TC (60-minute group exercise, 3 times/week), respectively. Their
      blood and urine samples were collected at the baseline, 1-, 3- and 6-months
      during intervention for assessing levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG),
      an oxidative DNA damage biomarker, and concentrations of serum and urine GTP
      components. RESULTS: The elevated concentrations of serum and urinary GTP
      components demonstrated a good adherence for the trial. A significant reduction
      of urinary 8-OHdG concentrations was found in all three treated groups during 3
      month (P<0.001) and 6-month (P<0.001) intervention, as compared to the placebo
      group. The significant time- and dose-effects on mitigation of the oxidative
      damage biomarker were also found for GTP, TC, and GTP+TC intervened groups.
      CONCLUSION: Our study demonstrated that GTP and TC interventions were effective
      strategies of reducing the levels of oxidative stress, a putative mechanism for
      osteoporosis in postmenopausal women, and more importantly, working in an
      additive manner, which holds the potential as alternative tools to improve bone
      health in this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT00625391.

PMID- 23118934
TI  - Possible impacts of the invasive plant Rubus niveus on the native vegetation of
      the Scalesia forest in the Galapagos islands.
AB  - Originally from Asia, Rubus niveus has become one of the most widespread invasive
      plant species in the Galapagos Islands. It has invaded open vegetation, shrubland
      and forest alike. It forms dense thickets up to 4 m high, appearing to displace
      native vegetation, and threaten the integrity of several native communities. This
      study used correlation analysis between a R. niveus cover gradient and a number
      of biotic (vascular plant species richness, cover and vegetation structure) and
      abiotic (light and soil properties) parameters to help understand possible
      impacts in one of the last remaining fragments of the Scalesia forest in Santa
      Cruz Island, Galapagos. Higher cover of R. niveus was associated with
      significantly lower native species richness and cover, and a different forest
      structure. Results illustrated that 60% R. niveus cover could be considered a
      threshold for these impacts. We suggest that a maximum of 40% R. niveus cover
      could be a suitable management target.

PMID- 23118933
TI  - PPARG binding landscapes in macrophages suggest a genome-wide contribution of
      PU.1 to divergent PPARG binding in human and mouse.
AB  - BACKGROUND: Genome-wide comparisons of transcription factor binding sites in
      different species can be used to evaluate evolutionary constraints that shape
      gene regulatory circuits and to understand how the interaction between
      transcription factors shapes their binding landscapes over evolution. RESULTS: We
      have compared the PPARG binding landscapes in macrophages to investigate the
      evolutionary impact on PPARG binding diversity in mouse and humans for this
      important nuclear receptor. Of note, only 5% of the PPARG binding sites were
      shared between the two species. In contrast, at the gene level, PPARG target
      genes conserved between both species constitute more than 30% of the target genes
      regulated by PPARG ligand in human macrophages. Moreover, the majority of all
      PPARG binding sites (55-60%) in macrophages show co-occupancy of the lineage
      specification factor PU.1 in both species. Exploring the evolutionary dynamics of
      PPARG binding sites, we observed that PU.1 co-binding to PPARG sites appears to
      be important for possible PPARG ancestral functions such as lipid metabolism.
      Thus we speculate that PU.1 may have guided utilization of these species-specific
      PPARG conserved binding sites in macrophages during evolution. CONCLUSIONS: We
      propose a model in which PU.1 sites may have served as "anchor" loci for the
      formation of new and functionally relevant PPARG binding sites throughout
      evolution. As PU.1 is an essential factor in macrophage biology, such an
      evolutionary mechanism would allow for the establishment of relevant PPARG
      regulatory modules in a PU.1-dependent manner and yet permit for nuanced
      regulatory changes in individual species.

PMID- 23118935
TI  - Modeling and dynamical analysis of virus-triggered innate immune signaling
      pathways.
AB  - The investigation of the dynamics and regulation of virus-triggered innate immune
      signaling pathways at a system level will enable comprehensive analysis of the
      complex interactions that maintain the delicate balance between resistance to
      infection and viral disease. In this study, we developed a delayed mathematical
      model to describe the virus-induced interferon (IFN) signaling process by
      considering several key players in the innate immune response. Using dynamic
      analysis and numerical simulation, we evaluated the following predictions
      regarding the antiviral responses: (1) When the replication ratio of virus is
      less than 1, the infectious virus will be eliminated by the immune system's
      defenses regardless of how the time delays are changed. (2) The IFN positive
      feedback regulation enhances the stability of the innate immune response and
      causes the immune system to present the bistability phenomenon. (3) The
      appropriate duration of viral replication and IFN feedback processes stabilizes
      the innate immune response. The predictions from the model were confirmed by
      monitoring the virus titer and IFN expression in infected cells. The results
      suggest that the balance between viral replication and IFN-induced feedback
      regulation coordinates the dynamical behavior of virus-triggered signaling and
      antiviral responses. This work will help clarify the mechanisms of the virus
      induced innate immune response at a system level and provide instruction for
      further biological experiments.

PMID- 23118936
TI  - Fasudil protects the heart against ischemia-reperfusion injury by attenuating
      endoplasmic reticulum stress and modulating SERCA activity: the differential role
      for PI3K/Akt and JAK2/STAT3 signaling pathways.
AB  - Disordered calcium homeostasis can lead to endoplasmic reticulum (ER) stress. Our
      previous data showed that time course activation of ER stress contributes to time
      related increase in ischemia-reperfusion (I/R) injury. However, it has not been
      tested whether PI3K/Akt and JAK2/STAT3 pathways play differential roles in
      reducing ER stress to protect the heart. In the present study, using fasudil
      which is a specific inhibitor of ROCK, we aimed to investigate whether improved
      SERCA expression and activity accounts for reduced ER stress by ROCK inhibition,
      specifically whether PI3K/Akt and JAK2/STAT3 pathways are differentially involved
      in modulating SERCA activity to reduce ER stress and hence I/R injury. The
      results showed that during the reperfusion period following 45 min of coronary
      ligation the infarct size (IS) increased from 3 h of reperfusion (45.4+/-5.57%)
      to 24 h reperfusion (64.21+/-5.43, P<0.05), which was associated with ER stress
      dependent apoptosis signaling activation including CHOP, Caspase-12 and JNK
      (P<0.05, respectively).The dynamic ER stress activation was also related to
      impaired SERCA activity at 24 h of reperfusion. Administration of fasudil at 10
      mg/Kg significantly attenuated ROCK activation during reperfusion and resulted in
      an improved SERCA activity which was closely associated with decreases in
      temporal activation of ER stress and IS changes. Interestingly, while both
      PI3K/Akt and JAK2/STAT3 signaling pathways played equal role in the protection
      offered by ROCK inhibition at 3 h of reperfusion, the rescued SERCA expression
      and activity at 24 h of reperfusion by fasudil was mainly due to JAK2/STAT3
      activation, in which PI3K/Akt signaling shared much less roles.

PMID- 23118937
TI  - Perinatal exposure to a high-fat diet is associated with reduced hepatic
      sympathetic innervation in one-year old male Japanese macaques.
AB  - Our group recently demonstrated that maternal high-fat diet (HFD) consumption is
      associated with non-alcoholic fatty liver disease, increased apoptosis, and
      changes in gluconeogenic gene expression and chromatin structure in fetal
      nonhuman primate (NHP) liver. However, little is known about the long-term
      effects that a HFD has on hepatic nervous system development in offspring, a
      system that plays an important role in regulating hepatic metabolism. Utilizing
      immunohistochemistry and Real-Time PCR, we quantified sympathetic nerve fiber
      density, apoptosis, inflammation, and other autonomic components in the livers of
      fetal and one-year old Japanese macaques chronically exposed to a HFD. We found
      that HFD exposure in-utero and throughout the postnatal period (HFD/HFD), when
      compared to animals receiving a CTR diet for the same developmental period
      (CTR/CTR), is associated with a 1.7 fold decrease in periportal sympathetic
      innervation, a 5 fold decrease in parenchymal sympathetic innervation, and a 2.5
      fold increase in hepatic apoptosis in the livers of one-year old male animals.
      Additionally, we observed an increase in hepatic inflammation and a decrease in a
      key component of the cholinergic anti-inflammatory pathway in one-year old
      HFD/HFD offspring. Taken together, these findings reinforce the impact that
      continuous exposure to a HFD has in the development of long-term hepatic
      pathologies in offspring and highlights a potential neuroanatomical basis for
      hepatic metabolic dysfunction.

PMID- 23118938
TI  - Functional lung imaging during HFV in preterm rabbits.
AB  - Although high frequency ventilation (HFV) is an effective mode of ventilation,
      there is limited information available in regard to lung dynamics during HFV. To
      improve the knowledge of lung function during HFV we have developed a novel lung
      imaging and analysis technique. The technique can determine complex lung motion
      information in vivo with a temporal resolution capable of observing HFV dynamics.
      Using high-speed synchrotron based phase contrast X-ray imaging and cross
      correlation analysis, this method is capable of recording data in more than 60
      independent regions across a preterm rabbit lung in excess of 300 frames per
      second (fps). This technique is utilised to determine regional intra-breath lung
      mechanics of preterm rabbit pups during HFV. Whilst ventilated at fixed
      pressures, each animal was ventilated at frequencies of 1, 3, 5 and 10 Hz. A 50%
      decrease in delivered tidal volume was measured at 10 Hz compared to 1 Hz, yet at
      the higher frequency a 500% increase in minute activity was measured.
      Additionally, HFV induced greater homogeneity of lung expansion activity
      suggesting this ventilation strategy potentially minimizes tissue damage and
      improves gas mixing. The development of this technique permits greater insight
      and further research into lung mechanics and may have implications for the
      improvement of ventilation strategies used to support severe pulmonary trauma and
      disease.

PMID- 23118939
TI  - Systemic injection of kainic acid differently affects LTP magnitude depending on
      its epileptogenic efficiency.
AB  - Seizures have profound impact on synaptic function and plasticity. While kainic
      acid is a popular method to induce seizures and to potentially affect synaptic
      plasticity, it can also produce physiological-like oscillations and trigger some
      forms of long-term potentiation (LTP). Here, we examine whether induction of LTP
      is altered in hippocampal slices prepared from rats with different sensitivity to
      develop status epilepticus (SE) by systemic injection of kainic acid. Rats were
      treated with multiple low doses of kainic acid (5 mg/kg; i.p.) to develop SE in a
      majority of animals (72-85% rats). A group of rats were resistant to develop SE
      (15-28%) after several accumulated doses. Animals were subsequently tested using
      chronic recordings and object recognition tasks before brain slices were prepared
      for histological studies and to examine basic features of hippocampal synaptic
      function and plasticity, including input/output curves, paired-pulse facilitation
      and theta-burst induced LTP. Consistent with previous reports in kindling and
      pilocapine models, LTP was reduced in rats that developed SE after kainic acid
      injection. These animals exhibited signs of hippocampal sclerosis and developed
      spontaneous seizures. In contrast, resistant rats did not become epileptic and
      had no signs of cell loss and mossy fiber sprouting. In slices from resistant
      rats, theta-burst stimulation induced LTP of higher magnitude when compared with
      control and epileptic rats. Variations on LTP magnitude correlate with animals'
      performance in a hippocampal-dependent spatial memory task. Our results suggest
      dissociable long-term effects of treatment with kainic acid on synaptic function
      and plasticity depending on its epileptogenic efficiency.

PMID- 23118942
TI  - The effects of juvenile stress on anxiety, cognitive bias and decision making in
      adulthood: a rat model.
AB  - Stress experienced in childhood is associated with an increased risk of
      developing psychiatric disorders in adulthood. These disorders are particularly
      characterized by disturbances to emotional and cognitive processes, which are not
      currently fully modeled in animals. Assays of cognitive bias have recently been
      used with animals to give an indication of their emotional/cognitive state. We
      used a cognitive bias test, alongside a traditional measure of anxiety (elevated
      plus maze), to investigate the effects of juvenile stress (JS) on adulthood
      behaviour using a rodent model. During the cognitive bias test, animals were
      trained to discriminate between two reward bowls based on a stimulus
      (rough/smooth sandpaper) encountered before they reached the bowls. One stimulus
      (e.g. rough) was associated with a lower value reward than the other (e.g.
      smooth). Once rats were trained, their cognitive bias was explored through the
      presentation of an ambiguous stimulus (intermediate grade sandpaper): a rat was
      classed as optimistic if it chose the bowl ordinarily associated with the high
      value reward. JS animals were lighter than controls, exhibited increased anxiety
      like behaviour in the elevated plus maze and were more optimistic in the
      cognitive bias test. This increased optimism may represent an optimal foraging
      strategy for these underweight animals. JS animals were also faster than controls
      to make a decision when presented with an ambiguous stimulus, suggesting altered
      decision making. These results demonstrate that stress in the juvenile phase can
      increase anxiety-like behaviour and alter cognitive bias and decision making in
      adulthood in a rat model.

PMID- 23118943
TI  - Gender obesity inequities are huge but differ greatly according to environment
      and socio-economics in a North African setting: a national cross-sectional study
      in Tunisia.
AB  - INTRODUCTION: Southern Mediterranean countries have experienced a marked increase
      in the prevalence of obesity whose consequences for gender related health
      inequities have been little studied. We assessed gender obesity inequalities and
      their environmental and socio-economic modifiers among Tunisian adults. METHODS:
      Cross-sectional survey in 2005; national, 3 level random cluster sample of 35-70
      years Tunisians (women: n = 2964, men: n = 2379). Overall adiposity was assessed
      by BMI = weight(kg)/height(m)(2) and obesity was BMI>=30, WHtR = waist
      circumference to height ratio defined abdominal obesity as WHtR>=0.6. Gender
      obesity inequality measure was women versus men Prevalence Proportion Odds-Ratio
      (OR); models featuring gender x covariate interaction assessed variation of
      gender obesity inequalities with area (urban versus rural), age, marital status
      or socio-economic position (profession, education, household income proxy).
      RESULTS: BMI was much higher among women (28.4(0.2)) versus men (25.3(0.1)),
      P<0.0001) as was obesity (37.0% versus 13.3%, OR = 3.8[3.1-7.4], P<0.0001) and
      abdominal obesity (42.6% versus 15.6%, 4.0[3.3-4.8], P<0.0001). Gender obesity
      inequalities (women versus men adjusted OR) were higher in urban (OR = 3.3[1.3
      8.7]) than rural (OR = 2.0[0.7-5.5]) areas. These gender obesity inequalities
      were lower for subjects with secondary education or more (OR = 3.3[1.3-8.6]),
      than among those with no schooling (OR = 6.9[2.0-23.3]). They were also lower for
      those with upper/intermediate profession (OR = 1.4[0.5-4.3]) or even
      employees/workers OR = 2.3[1.0-5.4] than those not professionaly active at all
      (OR = 3.3[1.3-8.6]). Similar results were observed for addominal obesity.
      CONCLUSION: The huge overall gender obesity inequities (women much more corpulent
      than men) were higher in urban settings, but lower among subjects of higher
      education and professional activity. Reasons for gender inequalities in obesity
      and their variation with socio-economic position should be sought so that
      appropriate policies to reduce these inequalities can be implemented in Tunisia
      and similar settings.

PMID- 23118940
TI  - Functional and transcriptome analysis reveals an acclimatization strategy for
      abiotic stress tolerance mediated by Arabidopsis NF-YA family members.
AB  - Nuclear Factor Y (NF-Y) is a heterotrimeric complex formed by NF-YA/NF-YB/NF-YC
      subunits that binds to the CCAAT-box in eukaryotic promoters. In contrast to
      other organisms, in which a single gene encodes each subunit, in plants gene
      families of over 10 members encode each of the subunits. Here we report that five
      members of the Arabidopsis thaliana NF-YA family are strongly induced by several
      stress conditions via transcriptional and miR169-related post-transcriptional
      mechanisms. Overexpression of NF-YA2, 7 and 10 resulted in dwarf late-senescent
      plants with enhanced tolerance to several types of abiotic stress. These
      phenotypes are related to alterations in sucrose/starch balance and cell
      elongation observed in NF-YA overexpressing plants. The use of transcriptomic
      analysis of transgenic plants that express miR169-resistant versions of NF-YA2,
      3, 7, and 10 under an estradiol inducible system, as well as a dominant-repressor
      version of NF-YA2 revealed a set of genes, whose promoters are enriched in NF-Y
      binding sites (CCAAT-box) and that may be directly regulated by the NF-Y complex.
      This analysis also suggests that NF-YAs could participate in modulating gene
      regulation through positive and negative mechanisms. We propose a model in which
      the increase in NF-YA transcript levels in response to abiotic stress is part of
      an adaptive response to adverse environmental conditions in which a reduction in
      plant growth rate plays a key role.

PMID- 23118941
TI  - Sildenafil enhances neurogenesis and oligodendrogenesis in ischemic brain of
      middle-aged mouse.
AB  - Adult neural stem cells give rise to neurons, oligodendrocytes and astrocytes.
      Aging reduces neural stem cells. Using an inducible nestin-CreER(T2)/R26R-yellow
      fluorescent protein (YFP) mouse, we investigated the effect of Sildenafil, a
      phosphodiesterase type 5 (PDE5) inhibitor, on nestin lineage neural stem cells
      and their progeny in the ischemic brain of the middle-aged mouse. We showed that
      focal cerebral ischemia induced nestin lineage neural stem cells in the
      subventricular zone (SVZ) of the lateral ventricles and nestin expressing NeuN
      positive neurons and adenomatous polyposis coli (APC) positive mature
      oligodendrocytes in the ischemic striatum and corpus callosum in the aged mouse.
      Treatment of the ischemic middle-aged mouse with Sildenafil increased nestin
      expressing neural stem cells, mature neurons, and oligodendrocytes by 33, 75, and
      30%, respectively, in the ischemic brain. These data indicate that Sildenafil
      amplifies nestin expressing neural stem cells and their neuronal and
      oligodendrocyte progeny in the ischemic brain of the middle-aged mouse.

PMID- 23118944
TI  - Evidence that a laminin-like insect protein mediates early events in the
      interaction of a Phytoparasite with its vector's salivary gland.
AB  - Phytomonas species are plant parasites of the family Trypanosomatidae, which are
      transmitted by phytophagous insects. Some Phytomonas species cause major
      agricultural damages. The hemipteran Oncopeltus fasciatus is natural and
      experimental host for several species of trypanosomatids, including Phytomonas
      spp. The invasion of the insect vectors' salivary glands is one of the most
      important events for the life cycle of Phytomonas species. In the present study,
      we show the binding of Phytomonas serpens at the external face of O. fasciatus
      salivary glands by means of scanning electron microscopy and the in vitro
      interaction of living parasites with total proteins from the salivary glands in
      ligand blotting assays. This binding occurs primarily through an interaction with
      a 130 kDa salivary gland protein. The mass spectrometry of the trypsin-digest of
      this protein matched 23% of human laminin-5 beta3 chain precursor sequence by 16
      digested peptides. A protein sequence search through the transcriptome of O.
      fasciatus embryo showed a partial sequence with 51% similarity to human laminin
      beta3 subunit. Anti-human laminin-5 beta3 chain polyclonal antibodies recognized
      the 130 kDa protein by immunoblotting. The association of parasites with the
      salivary glands was strongly inhibited by human laminin-5, by the purified 130
      kDa insect protein, and by polyclonal antibodies raised against the human laminin
      5 beta3 chain. This is the first report demonstrating that a laminin-like
      molecule from the salivary gland of O. fasciatus acts as a receptor for
      Phytomonas binding. The results presented in this investigation are important
      findings that will support further studies that aim at developing new approaches
      to prevent the transmission of Phytomonas species from insects to plants and vice
      versa.

PMID- 23118945
TI  - Lipoprotein-associated phospholipase A2 activity predicts cardiovascular events
      in high risk coronary artery disease patients.
AB  - OBJECTIVE: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is deemed to play a
      role in atherosclerosis and plaque destabilization as demonstrated in animal
      models and in prospective clinical studies. However, most of the literature is
      either focused on high-risk, apparently healthy patients, or is based on cross
      sectional studies. Therefore, we tested the hypothesis that serum Lp-PLA2 mass
      and activity are useful for predicting cardiovascular (CV) events over the
      coronary atherosclerotic burden and conventional risk factors in high-risk
      coronary artery disease patients. METHODS AND RESULTS: In a prospective cohort
      study of 712 Caucasian patients, who underwent coronary angiography and
      measurement of both Lp-PLA2 mass and activity at baseline, we determined incident
      CV events at follow-up after splitting the patients into a high and a low Lp-PLA2
      mass and activity groups based on ROC analysis and Youden index. Kaplan-Meier and
      propensity score matching analysis were used to compare CV event-free survival
      between groups. Follow-up data were obtained in 75% of the cohort after a median
      of 7.2 years (range 1-12.7 years) during which 129 (25.5%) CV events were
      observed. The high Lp-PLA2 activity patients showed worse CV event-free survival
      (66.7% vs. 79.5%, p = 0.023) and acute coronary syndrome-free survival (75.4% vs.
      85.6%, p = 0.04) than those in low Lp-PLA2 group. CONCLUSIONS: A high Lp-PLA2
      activity implies a worse CV prognosis at long term follow up in high-risk
      Caucasian patients referred for coronary angiography.

PMID- 23118946
TI  - Susceptibility of human head and neck cancer cells to combined inhibition of
      glutathione and thioredoxin metabolism.
AB  - Increased glutathione (GSH) and thioredoxin (Trx) metabolism are mechanisms that
      are widely implicated in resistance of cancer cells to chemotherapy. The current
      study determined if simultaneous inhibition of GSH and Trx metabolism enhanced
      cell killing of human head and neck squamous cell carcinoma (HNSCC) cells by a
      mechanism involving oxidative stress. Inhibition of GSH and Trx metabolism with
      buthionine sulfoximine (BSO) and auranofin (AUR), respectively, induced
      significant decreases in clonogenic survival compared to either drug alone in
      FaDu, Cal-27 and SCC-25 HNSCC cells in vitro and in vivo in Cal-27 xenografts.
      BSO+AUR significantly increased glutathione and thioredoxin oxidation and
      suppressed peroxiredoxin activity in vitro. Pre-treatment with N-acetylcysteine
      completely reversed BSO+AUR-induced cell killing in FaDu and Cal-27 cells, while
      catalase and selenium supplementation only inhibited BSO+AUR-induced cell killing
      in FaDu cells. BSO+AUR decreased caspase 3/7 activity in HNSCC cells and
      significantly reduced the viability of both Bax/Bak double knockout (DKO) and DKO
      Bax reconstituted hematopoietic cells suggesting that necrosis was involved.
      BSO+AUR also significantly sensitized FaDu, Cal-27, SCC-25 and SQ20B cells to
      cell killing induced by the EGFR inhibitor Erlotinib in vitro. These results
      support the conclusion that simultaneous inhibition of GSH and Trx metabolism
      pathways induces oxidative stress and clonogenic killing in HNSCCs and this
      strategy may be useful in sensitizing HNSCCs to EGFR inhibitors.

PMID- 23118948
TI  - Risk factors for metastatic castration-resistant prostate cancer (CRPC) predict
      long-term treatment with docetaxel.
AB  - PURPOSE: For patients with metastatic castration-resistant prostatic cancer
      (mCRPC), docetaxel plus prednisone leads to superior survival and a higher
      response rate compared with mitoxantrone plus prednisone. We analyzed the
      efficacy of long-term treatment with >=10 cycles of docetaxel, and validated the
      risk group classification in predicting overall survival (OS) in Japanese
      patients with mCRPC. PATIENTS AND METHODS: Fifty-two patients with mCRPC were
      administered 55 mg/m(2) docetaxel and 8 mg dexamethasone, every 3 or 4 weeks,
      simultaneously with hormonal therapy and daily oral dexamethasone. They were
      divided into two groups, short-term (9 or fewer cycles) and long-term (10 or more
      cycles). Four risk factors including the presence of anemia, bone metastases,
      significant pain and visceral metastases were utilized for the risk group
      classification. RESULTS: Fourteen patients (27%) had an elevation of PSA in spite
      of docetaxel treatment, while 23 patients (44%) had a decline in PSA level,
      including 9 patients (17%) whose PSA level declined by >=50%. The median duration
      of OS after the initiation of this therapy was 11.2 months in the short-term
      group and 28.5 months in the long-term group. The good risk group showed a
      significant difference in OS compared with the intermediate and poor risk groups
      (P<0.001). The median number of cycles of treatment was 14, 4 and 3 for each risk
      group, respectively (p<0.01). CONCLUSIONS: The present study indicated that >=10
      cycles of this docetaxel therapy can significantly prolong survival in Japanese
      men with CRPC. This risk group classification for men with mCRPC at the
      initiation of this chemotherapy is useful.

PMID- 23118947
TI  - Discovery and targeted LC-MS/MS of purified polerovirus reveals differences in
      the virus-host interactome associated with altered aphid transmission.
AB  - Circulative transmission of viruses in the Luteoviridae, such as cereal yellow
      dwarf virus (CYDV), requires a series of precisely orchestrated interactions
      between virus, plant, and aphid proteins. Natural selection has favored these
      viruses to be retained in the phloem to facilitate acquisition and transmission
      by aphids. We show that treatment of infected oat tissue homogenate with sodium
      sulfite reduces transmission of the purified virus by aphids. Transmission
      electron microscopy data indicated no gross change in virion morphology due to
      treatments. However, treated virions were not acquired by aphids through the
      hindgut epithelial cells and were not transmitted when injected directly into the
      hemocoel. Analysis of virus preparations using nanoflow liquid chromatography
      coupled to tandem mass spectrometry revealed a number of host plant proteins co
      purifying with viruses, some of which were lost following sodium sulfite
      treatment. Using targeted mass spectrometry, we show data suggesting that several
      of the virus-associated host plant proteins accumulated to higher levels in
      aphids that were fed on CYDV-infected plants compared to healthy plants. We
      propose two hypotheses to explain these observations, and these are not mutually
      exclusive: (a) that sodium sulfite treatment disrupts critical virion-host
      protein interactions required for aphid transmission, or (b) that host infection
      with CYDV modulates phloem protein expression in a way that is favorable for
      virus uptake by aphids. Importantly, the genes coding for the plant proteins
      associated with virus may be examined as targets in breeding cereal crops for new
      modes of virus resistance that disrupt phloem-virus or aphid-virus interactions.

PMID- 23118949
TI  - Prevalence of seropositivity to pandemic influenza A/H1N1 virus in the United
      States following the 2009 pandemic.
AB  - BACKGROUND: 2009 pandemic influenza A/H1N1 (A(H1N1)pdm09) was first detected in
      the United States in April 2009 and resulted in a global pandemic. We conducted a
      serologic survey to estimate the cumulative incidence of A(H1N1)pdm09 through the
      end of 2009 when pandemic activity had waned in the United States. METHODS: We
      conducted a pair of cross sectional serologic surveys before and after the
      spring/fall waves of the pandemic for evidence of seropositivity (titer >=40)
      using the hemagglutination inhibition (HI) assay. We tested a baseline sample of
      1,142 serum specimens from the 2007-2008 National Health and Nutrition
      Examination Survey (NHANES), and 2,759 serum specimens submitted for routine
      screening to clinical diagnostic laboratories from ten representative sites.
      RESULTS: The age-adjusted prevalence of seropositivity to A(H1N1)pdm09 by year
      end 2009 was 36.9% (95%CI: 31.7-42.2%). After adjusting for baseline cross
      reactive antibody, pandemic vaccination coverage and the sensitivity/specificity
      of the HI assay, we estimate that 20.2% (95%CI: 10.1-28.3%) of the population was
      infected with A(H1N1)pdm09 by December 2009, including 53.3% (95%CI: 39.0-67.1%)
      of children aged 5-17 years. CONCLUSIONS: By December 2009, approximately one
      fifth of the US population, or 61.9 million persons, may have been infected with
      A(H1N1)pdm09, including around half of school-aged children.

PMID- 23118951
TI  - Variation revealed by SNP genotyping and morphology provides insight into the
      origin of the tomato.
AB  - Tomato, Solanum lycopersicum, is divided into two widely distributed varieties:
      the cultivated S. lycopersicum var. lycopersicum, and the weedy S. lycopersicum
      var. cerasiforme. Solanum pimpinellifolium is the most closely related wild
      species of tomato.The roles of S. pimpinellifolium and S. l. cerasiforme during
      the domestication of tomato are still under debate. Some authors consider S. l.
      cerasiforme to be the ancestor, whereas others think that S. l. cerasiforme is an
      admixture of S. pimpinellifolium and the cultivated S. l. lycopersicum. It is
      also not clear whether the domestication occurred in the Andean region or in
      Mesoamerica. We characterized 272 accessions (63 S. pimpinellifolium, 106 S. l.
      cerasiforme, 95 S. l. lycopersicum and 8 derived from hybridization processes)
      were morphologically and genetically using the SolCap platform (7,414 SNPs). The
      two species were distinguished in a PCA analysis and displayed a rich geographic
      structure. Solanum lycopersicum var. cerasiforme and S. l. lycopersicum were also
      differentiated in the PCA and Structure analyses, which supports maintaining them
      as different varieties. Solanum pimpinellifolium and the Andean S. l. cerasiforme
      were more diverse than the non-Andean S. lycopersicum. Solanum lycopersicum var.
      cerasiforme was morphologically and molecularly intermediate between S.
      pimpinellifolium and tomato. Solanum lycopersicum var. cerasiforme, with the
      exception of several Ecuadorian and Mexican accessions, is composed of the
      products of admixture processes according to the Structure analysis. The non
      admixtured S. l. cerasiforme might be similar to the ancestral cultivars from
      which the cultivated tomato originated, and presents remarkable morphological
      diversity, including fruits of up to 6 cm in diameter. The data obtained would
      fit a model in which a pre-domestication took place in the Andean region, with
      the domestication being completed in Mesoamerica. Subsequently, the Spaniards
      took plants from Mesoamerica to Spain and from there they were exported to the
      rest of the world.

PMID- 23118950
TI  - Comparison of suprachoroidal drug delivery with subconjunctival and intravitreal
      routes using noninvasive fluorophotometry.
AB  - PURPOSE: To determine whether exposure of sodium fluorescein (NaF) to the choroid
      retina region in the posterior segment of the eye is greater with suprachoroidal
      injection when compared to intravitreal and transscleral routes. METHODS:
      Suprachoroidal injection, a new approach for drug delivery to the posterior
      segment of the eye was validated using a 34 G needle and Indian ink injections in
      Sprague Dawley rats, followed by histology. Delivery of NaF was compared in
      Sprague Dawley rats after suprachoroidal, posterior subconjunctival, or
      intravitreal injections. NaF levels were monitored noninvasively up to 6 hours
      using Fluorotron MasterTM, an ocular fluorophotometer Pharmacokinetic parameters
      were estimated using WinNonlin. RESULTS: Histological analysis indicated
      localization of India ink to the suprachoroidal space below sclera, following
      injection. NaF delivery to choroid-retina was in the order: suprachoroidal >
      intravitreal >posterior subconjunctival injection. Peak NaF concentration
      (C(max)) in choroid-retina was 36-fold (p = 0.001) and 25-fold (p = 0.001) higher
      after suprachoroidal (2744+/-1111 ng/ml) injection when compared to posterior
      subconjunctival (76+/-6 ng/ml) and intravitreal (108+/-39 ng/ml) injections,
      respectively. NaF exposure (AUC(0-360min)) to choroid-retina after suprachoroidal
      injection was 6-fold (p = 0.001) and 2-fold (p = 0.03) higher than posterior
      subconjunctival and intravitreal injections, respectively. Choroid-retina T(max)
      was observed immediately after dosing with suprachoroidal injections and at 10
      and 27.5 minutes, respectively, with subconjunctival and intravitreal injections.
      CONCLUSIONS: Suprachoroidal injections are feasible in a rat model.
      Suprachoroidal injections resulted in the highest bioavailability, that is, the
      extent and rate of delivery of NaF to choroid-retina, when compared to
      intravitreal and posterior subconjunctival injections. Ocular fluorophotometry is
      useful for noninvasive monitoring of NaF in rats following administration by
      various routes including suprachoroidal route.

PMID- 23118952
TI  - Predicting the location and spatial extent of submerged coral reef habitat in the
      Great Barrier Reef world heritage area, Australia.
AB  - AIM: Coral reef communities occurring in deeper waters have received little
      research effort compared to their shallow-water counterparts, and even such basic
      information as their location and extent are currently unknown throughout most of
      the world. Using the Great Barrier Reef as a case study, habitat suitability
      modelling is used to predict the distribution of deep-water coral reef
      communities on the Great Barrier Reef, Australia. We test the effectiveness of a
      range of geophysical and environmental variables for predicting the location of
      deep-water coral reef communities on the Great Barrier Reef. LOCATION: Great
      Barrier Reef, Australia. METHODS: Maximum entropy modelling is used to identify
      the spatial extent of two broad communities of habitat-forming megabenthos
      phototrophs and heterotrophs. Models were generated using combinations of
      geophysical substrate properties derived from multibeam bathymetry and
      environmental data derived from Bio-ORACLE, combined with georeferenced
      occurrence records of mesophotic coral communities from autonomous underwater
      vehicle, remotely operated vehicle and SCUBA surveys. Model results are used to
      estimate the total amount of mesophotic coral reef habitat on the GBR. RESULTS:
      Our models predict extensive but previously undocumented coral communities
      occurring both along the continental shelf-edge of the Great Barrier Reef and
      also on submerged reefs inside the lagoon. Habitat suitability for phototrophs is
      highest on submerged reefs along the outer-shelf and the deeper flanks of
      emergent reefs inside the GBR lagoon, while suitability for heterotrophs is
      highest in the deep waters along the shelf-edge. Models using only geophysical
      variables consistently outperformed models incorporating environmental data for
      both phototrophs and heterotrophs. MAIN CONCLUSION: Extensive submerged coral
      reef communities that are currently undocumented are likely to occur throughout
      the Great Barrier Reef. High-quality bathymetry data can be used to identify
      these reefs, which may play an important role in resilience of the GBR ecosystem
      to climate change.

PMID- 23118953
TI  - Disease risk in temperate amphibian populations is higher at closed-canopy sites.
AB  - Habitat loss and chytridiomycosis (a disease caused by the chytrid fungus
      Batrachochytrium dendrobatidis - Bd) are major drivers of amphibian declines
      worldwide. Habitat loss regulates host-pathogen interactions by altering biotic
      and abiotic factors directly linked to both host and pathogen fitness. Therefore,
      studies investigating the links between natural vegetation and chytridiomycosis
      require integrative approaches to control for the multitude of possible
      interactions of biological and environmental variables in spatial epidemiology.
      In this study, we quantified Bd infection dynamics across a gradient of natural
      vegetation and microclimates, looking for causal associations between vegetation
      cover, multiple microclimatic variables, and pathogen prevalence and infection
      intensity. To minimize the effects of host diversity in our analyses, we sampled
      amphibian populations in the Adirondack Mountains of New York State, a region
      with relatively high single-host dominance. We sampled permanent ponds for
      anurans, focusing on populations of the habitat generalist frog Lithobates
      clamitans, and recorded various biotic and abiotic factors that potentially
      affect host-pathogen interactions: natural vegetation, canopy density, water
      temperature, and host population and community attributes. We screened for
      important explanatory variables of Bd infections and used path analyses to
      statistically test for the strength of cascading effects linking vegetation
      cover, microclimate, and Bd parameters. We found that canopy density, natural
      vegetation, and daily average water temperature were the best predictors of Bd.
      High canopy density resulted in lower water temperature, which in turn predicted
      higher Bd prevalence and infection intensity. Our results confirm that
      microclimatic shifts arising from changes in natural vegetation play an important
      role in Bd spatial epidemiology, with areas of closed canopy favoring Bd. Given
      increasing rates of anthropogenic habitat modification and the resulting declines
      in temperate and tropical frogs, understanding how vegetation cover and disease
      interact is critical for predicting Bd spread and developing appropriate
      management tools for wild populations.

PMID- 23118954
TI  - Dynamic hubs show competitive and static hubs non-competitive regulation of their
      interaction partners.
AB  - Date hub proteins have 1 or 2 interaction interfaces but many interaction
      partners. This raises the question of whether all partner proteins compete for
      the interaction interface of the hub or if the cell carefully regulates aspects
      of this process? Here, we have used real-time rendering of protein interaction
      networks to analyse the interactions of all the 1 or 2 interface hubs of
      Saccharomyces cerevisiae during the cell cycle. By integrating previously
      determined structural and gene expression data, and visually hiding the nodes
      (proteins) and their edges (interactions) during their troughs of expression, we
      predict when interactions of hubs and their partners are likely to exist. This
      revealed that 20 out of all 36 one- or two- interface hubs in the yeast
      interactome fell within two main groups. The first was dynamic hubs with static
      partners, which can be considered as 'competitive hubs'. Their interaction
      partners will compete for the interaction interface of the hub and the success of
      any interaction will be dictated by the kinetics of interaction (abundance and
      affinity) and subcellular localisation. The second was static hubs with dynamic
      partners, which we term 'non-competitive hubs'. Regulatory mechanisms are finely
      tuned to lessen the presence and/or effects of competition between the
      interaction partners of the hub. It is possible that these regulatory processes
      may also be used by the cell for the regulation of other, non-cell cycle
      processes.

PMID- 23118955
TI  - Ppm1-encoded polyprenyl monophosphomannose synthase activity is essential for
      lipoglycan synthesis and survival in mycobacteria.
AB  - The biosynthesis of mycobacterial mannose-containing lipoglycans, such as
      lipomannan (LM) and the immunomodulator lipoarabinomanan (LAM), is carried out by
      the GT-C superfamily of glycosyltransferases that require polyprenylphosphate
      based mannose (PPM) as a sugar donor. The essentiality of lipoglycan synthesis
      for growth makes the glycosyltransferase that synthesizes PPM, a potential drug
      target in Mycobacterium tuberculosis, the causative agent of tuberculosis. In M.
      tuberculosis, PPM has been shown to be synthesized by Ppm1 in enzymatic assays.
      However, genetic evidence for its essentiality and in vivo role in LM/LAM and PPM
      biosynthesis is lacking. In this study, we demonstrate that MSMEG3859, a
      Mycobacterium smegmatis gene encoding the homologue of the catalytic domain of M.
      tuberculosis Ppm1, is essential for survival. Depletion of MSMEG3859 in a
      conditional mutant of M. smegmatis resulted in the loss of higher order
      phosphatidyl-myo-inositol mannosides (PIMs) and lipomannan. We were also able to
      demonstrate that two other M. tuberculosis genes encoding glycosyltransferases
      that either had been shown to possess PPM synthase activity (Rv3779), or were
      involved in synthesizing similar polyprenol-linked donors (ppgS), were unable to
      compensate for the loss of MSMEG3859 in the conditional mutant.

PMID- 23118956
TI  - Forgetting what was where: the fragility of object-location binding.
AB  - Although we frequently take advantage of memory for objects locations in everyday
      life, understanding how an object's identity is bound correctly to its location
      remains unclear. Here we examine how information about object identity, location
      and crucially object-location associations are differentially susceptible to
      forgetting, over variable retention intervals and memory load. In our task,
      participants relocated objects to their remembered locations using a touchscreen.
      When participants mislocalized objects, their reports were clustered around the
      locations of other objects in the array, rather than occurring randomly. These
      'swap' errors could not be attributed to simple failure to remember either the
      identity or location of the objects, but rather appeared to arise from failure to
      bind object identity and location in memory. Moreover, such binding failures
      significantly contributed to decline in localization performance over retention
      time. We conclude that when objects are forgotten they do not disappear
      completely from memory, but rather it is the links between identity and location
      that are prone to be broken over time.

PMID- 23118957
TI  - Disruption of the human gut microbiota following Norovirus infection.
AB  - The gut microbiota, the collection of all bacterial members in the intestinal
      tract, plays a key role in health. Disruption of the indigenous microbiota by a
      variety of stressors, including antibiotic therapy and intestinal infections, is
      associated with multiple health problems. We sought to determine if infection
      with Norovirus disrupts the gut microbiota. Barcoded pyrosequencing of the 16S
      rRNA-encoding gene was used to characterize the stool microbiota in Norovirus
      infected human patients (n = 38). While the microbiota in most infected patients
      (n = 31) resembled that seen in uninfected healthy controls, a minority of
      patients (n = 7) possessed a significantly altered microbiota characterized by
      reduced relative numbers of Bacteriodetes and a corresponding increase in
      Proteobacteria. In these patients, the increase in Proteobacteria was due to a
      single operational taxonomic unit (OTU) of Escherichia coli. We cultured E. coli
      from Norovirus-infected patients and characterized them using PCR-ribotyping and
      virulence factor analysis. Multiple ribotypes were encountered, but none
      possessed typical virulence factors commonly carried by enteropathogenic E. coli
      strains. Microbiota disruption and elevated Proteobacteria were not significantly
      correlated to patient age, gender, sampling time following illness onset, or
      overall gut inflammation. These results demonstrate that some patients have a
      disrupted microbiota following Norovirus infection, and therefore may be at
      elevated risk for long-term health complications.

PMID- 23118958
TI  - Is buffer a good proxy for a crowded cell-like environment? A comparative NMR
      study of calmodulin side-chain dynamics in buffer and E. coli lysate.
AB  - Biophysical studies of protein structure and dynamics are typically performed in
      a highly controlled manner involving only the protein(s) of interest.
      Comparatively fewer such studies have been carried out in the context of a
      cellular environment that typically involves many biomolecules, ions and
      metabolites. Recently, solution NMR spectroscopy, focusing primarily on backbone
      amide groups as reporters, has emerged as a powerful technique for investigating
      protein structure and dynamics in vivo and in crowded "cell-like" environments.
      Here we extend these studies through a comparative analysis of Ile, Leu, Val and
      Met methyl side-chain motions in apo, Ca(2+)-bound and Ca(2+), peptide-bound
      calmodulin dissolved in aqueous buffer or in E. coli lysate. Deuterium spin
      relaxation experiments, sensitive to pico- to nano-second time-scale processes
      and Carr-Purcell-Meiboom-Gill relaxation dispersion experiments, reporting on
      millisecond dynamics, have been recorded. Both similarities and differences in
      motional properties are noted for calmodulin dissolved in buffer or in lysate.
      These results emphasize that while significant insights can be obtained through
      detailed "test-tube" studies, experiments performed under conditions that are
      "cell-like" are critical for obtaining a comprehensive understanding of protein
      motion in vivo and therefore for elucidating the relation between motion and
      function.

PMID- 23118959
TI  - MicroRNA prediction using a fixed-order Markov model based on the secondary
      structure pattern.
AB  - Predicting miRNAs is an arduous task, due to the diversity of the precursors and
      complexity of enzyme processes. Although several prediction approaches have
      reached impressive performances, few of them could achieve a full-function
      recognition of mature miRNA directly from the candidate hairpins across species.
      Therefore, researchers continue to seek a more powerful model close to biological
      recognition to miRNA structure. In this report, we describe a novel miRNA
      prediction algorithm, known as FOMmiR, using a fixed-order Markov model based on
      the secondary structural pattern. For a training dataset containing 809 human pre
      miRNAs and 6441 human pseudo-miRNA hairpins, the model's parameters were defined
      and evaluated. The results showed that FOMmiR reached 91% accuracy on the human
      dataset through 5-fold cross-validation. Moreover, for the independent test
      datasets, the FOMmiR presented an outstanding prediction in human and other
      species including vertebrates, Drosophila, worms and viruses, even plants, in
      contrast to the well-known algorithms and models. Especially, the FOMmiR was not
      only able to distinguish the miRNA precursors from the hairpins, but also locate
      the position and strand of the mature miRNA. Therefore, this study provides a new
      generation of miRNA prediction algorithm, which successfully realizes a full
      function recognition of the mature miRNAs directly from the hairpin sequences.
      And it presents a new understanding of the biological recognition based on the
      strongest signal's location detected by FOMmiR, which might be closely associated
      with the enzyme cleavage mechanism during the miRNA maturation.

PMID- 23118961
TI  - Topographic variation in aboveground biomass in a subtropical evergreen broad
      leaved forest in China.
AB  - The subtropical forest biome occupies about 25% of China, with species diversity
      only next to tropical forests. Despite the recognized importance of subtropical
      forest in regional carbon storage and cycling, uncertainties remain regarding the
      carbon storage of subtropical forests, and few studies have quantified within
      site variation of biomass, making it difficult to evaluate the role of these
      forests in the global and regional carbon cycles. Using data for a 24-ha census
      plot in east China, we quantify aboveground biomass, characterize its spatial
      variation among different habitats, and analyse species relative contribution to
      the total aboveground biomass of different habitats. The average aboveground
      biomass was 223.0 Mg ha(-1) (bootstrapped 95% confidence intervals [217.6,
      228.5]) and varied substantially among four topographically defined habitats,
      from 180.6 Mg ha(-1) (bootstrapped 95% CI [167.1, 195.0]) in the upper ridge to
      245.9 Mg ha(-1) (bootstrapped 95% CI [238.3, 253.8]) in the lower ridge, with
      upper and lower valley intermediate. In consistent with our expectation,
      individual species contributed differently to the total aboveground biomass of
      different habitats, reflecting significant species habitat associations.
      Different species show differently in habitat preference in terms of biomass
      contribution. These patterns may be the consequences of ecological strategies
      difference among different species. Results from this study enhance our ability
      to evaluate the role of subtropical forests in the regional carbon cycle and
      provide valuable information to guide the protection and management of
      subtropical broad-leaved forest for carbon sequestration and carbon storage.

PMID- 23118960
TI  - The rice B-box zinc finger gene family: genomic identification, characterization,
      expression profiling and diurnal analysis.
AB  - BACKGROUND: The B-box (BBX) -containing proteins are a class of zinc finger
      proteins that contain one or two B-box domains and play important roles in plant
      growth and development. The Arabidopsis BBX gene family has recently been re
      identified and renamed. However, there has not been a genome-wide survey of the
      rice BBX (OsBBX) gene family until now. METHODOLOGY/PRINCIPAL FINDINGS: In this
      study, we identified 30 rice BBX genes through a comprehensive bioinformatics
      analysis. Each gene was assigned a uniform nomenclature. We described the
      chromosome localizations, gene structures, protein domains, phylogenetic
      relationship, whole life-cycle expression profile and diurnal expression patterns
      of the OsBBX family members. Based on the phylogeny and domain constitution, the
      OsBBX gene family was classified into five subfamilies. The gene duplication
      analysis revealed that only chromosomal segmental duplication contributed to the
      expansion of the OsBBX gene family. The expression profile of the OsBBX genes was
      analyzed by Affymetrix GeneChip microarrays throughout the entire life-cycle of
      rice cultivar Zhenshan 97 (ZS97). In addition, microarray analysis was performed
      to obtain the expression patterns of these genes under light/dark conditions and
      after three phytohormone treatments. This analysis revealed that the expression
      patterns of the OsBBX genes could be classified into eight groups. Eight genes
      were regulated under the light/dark treatments, and eleven genes showed
      differential expression under at least one phytohormone treatment. Moreover, we
      verified the diurnal expression of the OsBBX genes using the data obtained from
      the Diurnal Project and qPCR analysis, and the results indicated that many of
      these genes had a diurnal expression pattern. CONCLUSIONS/SIGNIFICANCE: The
      combination of the genome-wide identification and the expression and diurnal
      analysis of the OsBBX gene family should facilitate additional functional studies
      of the OsBBX genes.

PMID- 23118962
TI  - Molecular basis for modulation of the p53 target selectivity by KLF4.
AB  - The tumour suppressor p53 controls transcription of various genes involved in
      apoptosis, cell-cycle arrest, DNA repair and metabolism. However, its DNA
      recognition specificity is not nearly sufficient to explain binding to specific
      locations in vivo. Here, we present evidence that KLF4 increases the DNA-binding
      affinity of p53 through the formation of a loosely arranged ternary complex on
      DNA. This effect depends on the distance between the response elements of KLF4
      and p53. Using nuclear magnetic resonance and fluorescence techniques, we found
      that the amino-terminal domain of p53 interacts with the KLF4 zinc fingers and
      mapped the interaction site. The strength of this interaction was increased by
      phosphorylation of the p53 N-terminus, particularly on residues associated with
      regulation of cell-cycle arrest genes. Taken together, the cooperative binding of
      KLF4 and p53 to DNA exemplifies a regulatory mechanism that contributes to p53
      target selectivity.

PMID- 23118963
TI  - Rickettsia species in African Anopheles mosquitoes.
AB  - BACKGROUND: There is higher rate of R. felis infection among febrile patients
      than in healthy people in Sub-Saharan Africa, predominantly in the rainy season.
      Mosquitoes possess a high vectorial capacity and, because of their abundance and
      aggressiveness, likely play a role in rickettsial epidemiology.
      METHODOLOGY/PRINCIPAL FINDINGS: Quantitative and traditional PCR assays specific
      for Rickettsia genes detected rickettsial DNA in 13 of 848 (1.5%) Anopheles
      mosquitoes collected from Cote d'Ivoire, Gabon, and Senegal. R. felis was
      detected in one An. gambiae molecular form S mosquito collected from Kahin, Cote
      d'Ivoire (1/77, 1.3%). Additionally, a new Rickettsia genotype was detected in
      five An. gambiae molecular form S mosquitoes collected from Cote d'Ivoire (5/77,
      6.5%) and one mosquito from Libreville, Gabon (1/88, 1.1%), as well as six An.
      melas (6/67, 9%) mosquitoes collected from Port Gentil, Gabon. A sequence
      analysis of the gltA, ompB, ompA and sca4 genes indicated that this new
      Rickettsia sp. is closely related to R. felis. No rickettsial DNA was detected
      from An. funestus, An. arabiensis, or An. gambiae molecular form M mosquitoes.
      Additionally, a BLAST analysis of the gltA sequence from the new Rickettsia sp.
      resulted in a 99.71% sequence similarity to a species (JQ674485) previously
      detected in a blood sample of a Senegalese patient with a fever from the
      Bandafassi village, Kedougou region. CONCLUSION: R. felis was detected for the
      first time in An. gambiae molecular form S, which represents the major African
      malaria vector. The discovery of R. felis, as well as a new Rickettsia species,
      in mosquitoes raises new issues with respect to African rickettsial epidemiology
      that need to be investigated, such as bacterial isolation, the degree of the
      vectorial capacity of mosquitoes, the animal reservoirs, and human pathogenicity.

PMID- 23118964
TI  - Trends in prevalence of hypertension in Brazil: a systematic review with meta
      analysis.
AB  - BACKGROUND: The prevalence of hypertension in emerging nations was scarcely
      described to date. In Brazil, many population-based surveys evaluated the
      prevalence in cities throughout the country. However, there is no population
      based nationwide study of prevalence of hypertension. In this study, we estimated
      the prevalence of hypertension for the country and analyzed the trends for the
      last three decades. METHODS: Cross-sectional and cohort studies conducted from
      1980 to 2010 were independently identified by two reviewers, without language
      restriction, in the PubMed, Embase, LILACS, and Scielo electronic databases.
      Unpublished studies were identified in the Brazilian electronic database of
      theses and in annals of Cardiology congresses and meetings. In total, 40 studies
      were selected, comprising 122,018 individuals. RESULTS: Summary estimates of
      prevalence by the former WHO criteria (BP>=160/95 mmHg) in the 1980's and 1990's
      were 23.6% (95% CI 17.3-31.4%) and 19.6% (16.4-23.3%) respectively. The
      prevalence of hypertension by the JNC criteria (BP>=140/90 mmHg) in the 1980's,
      1990's and 2000's were 36.1% (95% CI 28.7-44.2%), 32.9% (29.9-36.0%), and 28.7%
      (26.2-31.4%), respectively (P<0.001). In the 2000's, the pooled prevalence
      estimates of self-reported hypertension on telephone inquiries was 20.6% (19.0
      22.4%), and of self-reported hypertension in home surveys was 25.2% (23.3-27.2%).
      CONCLUSIONS: The prevalence of hypertension in Brazil seems to have diminished 6%
      in the last three decades, but it still is approximately 30%. Nationwide surveys
      by self-reporting by telephone interviews underestimate the real prevalence.
      Rates of blood pressure control decreased in the same period, corresponding
      currently to only one quarter of individuals with hypertension.

PMID- 23118966
TI  - BCL2A1a over-expression in murine hematopoietic stem and progenitor cells
      decreases apoptosis and results in hematopoietic transformation.
AB  - We previously reported the development of a lethal myeloid sarcoma in a non-human
      primate model utilizing retroviral vectors to genetically modify hematopoietic
      stem and progenitor cells. This leukemia was characterized by insertion of the
      vector provirus into the BCL2A1 gene, with resultant BCL2A1 over-expression.
      There is little information on the role of this anti-apoptotic member of the BCL2
      family in hematopoiesis or leukemia induction. Therefore we studied the impact of
      Bcl2a1a lentiviral over-expression on murine hematopoietic stem and progenitor
      cells. We demonstrated the anti-apoptotic function of this protein in
      hematopoietic cells, but did not detect any impact of Bcl2a1a on in vitro cell
      growth or cell cycle kinetics. In vivo, we showed a higher propensity of HSCs
      over-expressing Bcl2a1a to engraft and contribute to hematopoiesis. Mice over
      expressing Bcl2a1a in the hematologic compartment eventually developed an
      aggressive malignant disease characterized as a leukemia/lymphoma of B-cell
      origin. Secondary transplants carried out to investigate the primitive origin of
      the disease revealed the leukemia was transplantable. Thus, Bcl2a1 should be
      considered as a proto-oncogene with a potential role in both lymphoid and myeloid
      leukemogenesis, and a concerning site for insertional activation by integrating
      retroviral vectors utilized in hematopoietic stem cell gene therapy.

PMID- 23118965
TI  - Cellular and molecular effect of MEHP Involving LXRalpha in human fetal testis
      and ovary.
AB  - BACKGROUND: Phthalates have been shown to have reprotoxic effects in rodents and
      human during fetal life. Previous studies indicate that some members of the
      nuclear receptor (NR) superfamilly potentially mediate phthalate effects. This
      study aimed to assess if expression of these nuclear receptors are modulated in
      the response to MEHP exposure on the human fetal gonads in vitro.
      METHODOLOGY/PRINCIPAL FINDINGS: Testes and ovaries from 7 to 12 gestational weeks
      human fetuses were exposed to 10(-4)M MEHP for 72 h in vitro. Transcriptional
      level of NRs and of downstream genes was then investigated using TLDA (TaqMan Low
      Density Array) and qPCR approaches. To determine whether somatic or germ cells of
      the testis are involved in the response to MEHP exposure, we developed a highly
      efficient cytometric germ cell sorting approach. In vitro exposure of fetal
      testes and ovaries to MEHP up-regulated the expression of LXRalpha, SREBP members
      and of downstream genes involved in the lipid and cholesterol synthesis in the
      whole gonad. In sorted testicular cells, this effect is only observable in
      somatic cells but not in the gonocytes. Moreover, the germ cell loss induced by
      MEHP exposure, that we previously described, is restricted to the male gonad as
      oogonia density is not affected in vitro. CONCLUSIONS/SIGNIFICANCE: We evidenced
      for the first time that phthalate increases the levels of mRNA for LXRalpha, and
      SREBP members potentially deregulating lipids/cholesterol synthesis in human
      fetal gonads. Interestingly, this novel effect is observable in both male and
      female whereas the germ cell apoptosis is restricted to the male gonad.
      Furthermore, we presented here a novel and potentially very useful flow
      cytometric cell sorting method to analyse molecular changes in germ cells versus
      somatic cells.

PMID- 23118967
TI  - Phylogeny-based comparative methods question the adaptive nature of sporophytic
      specializations in mosses.
AB  - Adaptive evolution has often been proposed to explain correlations between
      habitats and certain phenotypes. In mosses, a high frequency of species with
      specialized sporophytic traits in exposed or epiphytic habitats was, already 100
      years ago, suggested as due to adaptation. We tested this hypothesis by
      contrasting phylogenetic and morphological data from two moss families,
      Neckeraceae and Lembophyllaceae, both of which show parallel shifts to a
      specialized morphology and to exposed epiphytic or epilithic habitats. Phylogeny
      based tests for correlated evolution revealed that evolution of four sporophytic
      traits is correlated with a habitat shift. For three of them, evolutionary rates
      of dual character-state changes suggest that habitat shifts appear prior to
      changes in morphology. This suggests that they could have evolved as adaptations
      to new habitats. Regarding the fourth correlated trait the specialized morphology
      had already evolved before the habitat shift. In addition, several other
      specialized "epiphytic" traits show no correlation with a habitat shift. Besides
      adaptive diversification, other processes thus also affect the match between
      phenotype and environment. Several potential factors such as complex genetic and
      developmental pathways yielding the same phenotypes, differences in strength of
      selection, or constraints in phenotypic evolution may lead to an inability of
      phylogeny-based comparative methods to detect potential adaptations.

PMID- 23118968
TI  - Sanitary pad interventions for girls' education in Ghana: a pilot study.
AB  - BACKGROUND: Increased education of girls in developing contexts is associated
      with a number of important positive health, social, and economic outcomes for a
      community. The event of menarche tends to coincide with girls' transitions from
      primary to secondary education and may constitute a barrier for continued school
      attendance and performance. Following the MRC Framework for Complex
      Interventions, a pilot controlled study was conducted in Ghana to assess the role
      of sanitary pads in girls' education. METHODS: A sample of 120 schoolgirls
      between the ages of 12 and 18 from four villages in Ghana participated in a non
      randomized trial of sanitary pad provision with education. The trial had three
      levels of treatment: provision of pads with puberty education; puberty education
      alone; or control (no pads or education). The primary outcome was school
      attendance. RESULTS: After 3 months, providing pads with education significantly
      improved attendance among participants, (lambda 0.824, F = 3.760, p<.001). After
      5 months, puberty education alone improved attendance to a similar level (M =
      91.26, SD = 7.82) as sites where pads were provided with puberty education (Rural
      M = 89.74, SD = 9.34; Periurban M = 90.54, SD = 17.37), all of which were higher
      than control (M = 84.48, SD = 12.39). The total improvement through pads with
      education intervention after 5 months was a 9% increase in attendance. After 3
      months, providing pads with education significantly improved attendance among
      participants. The changes in attendance at the end of the trial, after 5 months,
      were found to be significant by site over time. With puberty education alone
      resulting in a similar attendance level. CONCLUSION: This pilot study
      demonstrated promising results of a low-cost, rapid-return intervention for
      girls' education in a developing context. Given the considerable development
      needs of poorer countries and the potential of young women there, these results
      suggest that a large-scale cluster randomized trial is warranted. TRIAL
      REGISTRATION: Pan African Clinical Trials Registry PACTR201202000361337.

PMID- 23118969
TI  - Neuroprotective actions of methylene blue and its derivatives.
AB  - Methylene blue (MB), the first lead chemical structure of phenothiazine and other
      derivatives, is commonly used in diagnostic procedures and as a treatment for
      methemoglobinemia. We have previously demonstrated that MB could function as an
      alternative mitochondrial electron transfer carrier, enhance cellular oxygen
      consumption, and provide protection in vitro and in rodent models of Parkinson's
      disease and stroke. In the present study, we investigated the structure-activity
      relationships of MB in vitro using MB and six structurally related compounds. MB
      reduces mitochondrial superoxide production via alternative electron transfer
      that bypasses mitochondrial complexes I-III. MB mitigates reactive free radical
      production and provides neuroprotection in HT-22 cells against glutamate, IAA and
      rotenone toxicity. Distinctly, MB provides no protection against direct oxidative
      stress induced by glucose oxidase. Substitution of a side chain at MB's 10
      nitrogen rendered a 1000-fold reduction of the protective potency against
      glutamate neurototoxicity. Compounds without side chains at positions 3 and 7,
      chlorophenothiazine and phenothiazine, have distinct redox potentials compared to
      MB and are incapable of enhancing mitochondrial electron transfer, while
      obtaining direct antioxidant actions against glutamate, IAA, and rotenone
      insults. Chlorophenothiazine exhibited direct antioxidant actions in mitochondria
      lysate assay compared to MB, which required reduction by NADH and mitochondria.
      MB increased complex IV expression and activity, while 2-chlorphenothiazine had
      no effect. Our study indicated that MB could attenuate superoxide production by
      functioning as an alternative mitochondrial electron transfer carrier and as a
      regenerable anti-oxidant in mitochondria.

PMID- 23118970
TI  - Reproducibility of Frankfort horizontal plane on 3D multi-planar reconstructed MR
      images.
AB  - OBJECTIVE: The purpose of this study was to determine the accuracy and
      reliability of Frankfort horizontal plane identification using displays of multi
      planar reconstructed MRI images, and propose it as a sufficiently stable and
      standardized reference plane for craniofacial structures. MATERIALS AND METHODS:
      MRI images of 43 subjects were obtained from the longitudinal population based
      cohort study SHIP-2 using a T1-weighted 3D sequence. Five examiners independently
      identified the three landmarks that form FH plane. Intra-examiner reproducibility
      and inter-examiner reliability, correlation coefficients (ICC), coefficient of
      variability and Bland-Altman plots were obtained for all landmarks coordinates to
      assess reproducibility. Intra-examiner reproducibility and inter-examiner
      reliability in terms of location and plane angulation were also assessed.
      RESULTS: Intra- and inter-examiner reliabilities for X, Y and Z coordinates of
      all three landmarks were excellent with ICC values ranging from 0.914 to 0.998.
      Differences among examiners were more in X and Z than in Y dimensions. The Bland
      Altman analysis demonstrated excellent intra- as well as inter-examiner agreement
      between examiners in all coordinates for all landmarks. Intra-examiner
      reproducibility and inter-examiner reliability of the three landmarks in terms of
      distance showed mean differences between 1.3 to 2.9 mm, Mean differences in plane
      angulation were between 1.0 degrees  to 1.5 degrees  among examiners. CONCLUSION:
      This study revealed excellent intra-examiner reproducibility and inter-examiner
      reliability of Frankfort Horizontal plane through 3D landmark identification in
      MRI. Sufficiently stable landmark-based reference plane could be used for
      different treatments and studies.

PMID- 23118971
TI  - Genetic modification of the soybean to enhance the beta-carotene content through
      seed-specific expression.
AB  - The carotenoid biosynthetic pathway was genetically manipulated using the
      recombinant PAC (Phytoene synthase-2A-Carotene desaturase) gene in Korean soybean
      (Glycine max L. cv. Kwangan). The PAC gene was linked to either the beta
      conglycinin (beta) or CaMV-35S (35S) promoter to generate beta-PAC and 35S-PAC
      constructs, respectively. A total of 37 transgenic lines (19 for beta-PAC and 18
      for 35S-PAC) were obtained through Agrobacterium-mediated transformation using
      the modified half-seed method. The multi-copy insertion of the transgene was
      determined by genomic Southern blot analysis. Four lines for beta-PAC were
      selected by visual inspection to confirm an orange endosperm, which was not found
      in the seeds of the 35S-PAC lines. The strong expression of PAC gene was detected
      in the seeds of the beta-PAC lines and in the leaves of the 35S-PAC lines by RT
      PCR and qRT-PCR analyses, suggesting that these two different promoters function
      distinctively. HPLC analysis of the seeds and leaves of the T(2) generation
      plants revealed that the best line among the beta-PAC transgenic seeds
      accumulated 146 ug/g of total carotenoids (approximately 62-fold higher than non
      transgenic seeds), of which 112 ug/g (77%) was beta-carotene. In contrast, the
      level and composition of the leaf carotenoids showed little difference between
      transgenic and non-transgenic soybean plants. We have therefore demonstrated the
      production of a high beta-carotene soybean through the seed-specific
      overexpression of two carotenoid biosynthetic genes, Capsicum phytoene synthase
      and Pantoea carotene desaturase. This nutritional enhancement of soybean seeds
      through the elevation of the provitamin A content to produce biofortified food
      may have practical health benefits in the future in both humans and livestock.

PMID- 23118972
TI  - p-Coumaric acid influenced cucumber rhizosphere soil microbial communities and
      the growth of Fusarium oxysporum f.sp. cucumerinum Owen.
AB  - BACKGROUND: Autotoxicity of cucumber root exudates or decaying residues may be
      the cause of the soil sickness of cucumber. However, how autotoxins affect soil
      microbial communities is not yet fully understood. METHODOLOGY/PRINCIPAL
      FINDINGS: The aims of this study were to study the effects of an artificially
      applied autotoxin of cucumber, p-coumaric acid, on cucumber seedling growth,
      rhizosphere soil microbial communities, and Fusarium oxysporum f.sp. cucumerinum
      Owen (a soil-borne pathogen of cucumber) growth. Abundance, structure and
      composition of rhizosphere bacterial and fungal communities were analyzed with
      real-time PCR, PCR-denaturing gradient gel electrophoresis (DGGE) and clone
      library methods. Soil dehydrogenase activity and microbial biomass C (MBC) were
      determined to indicate the activity and size of the soil microflora. Results
      showed that p-coumaric acid (0.1-1.0 umol/g soil) decreased cucumber leaf area,
      and increased soil dehydrogenase activity, MBC and rhizosphere bacterial and
      fungal community abundances. p-Coumaric acid also changed the structure and
      composition of rhizosphere bacterial and fungal communities, with increases in
      the relative abundances of bacterial taxa Firmicutes, Betaproteobacteria,
      Gammaproteobacteria and fungal taxa Sordariomycete, Zygomycota, and decreases in
      the relative abundances of bacterial taxa Bacteroidetes, Deltaproteobacteria,
      Planctomycetes, Verrucomicrobia and fungal taxon Pezizomycete. In addition, p
      coumaric acid increased Fusarium oxysporum population densities in soil.
      CONCLUSIONS/SIGNIFICANCE: These results indicate that p-coumaric acid may play a
      role in the autotoxicity of cucumber via influencing soil microbial communities.

PMID- 23118973
TI  - The evolution of academic performance in nine subspecialties of internal
      medicine: an analysis of journal citation reports from 1998 to 2010.
AB  - BACKGROUND: Internal medicine includes several subspecialties. This study aimed
      to describe change trend of impact factors in different subspecialties of
      internal medicine during the past 12 years, as well as the developmental
      differences among each subspecialty, and the possible influencing factors behind
      these changes and differences. METHODS: Nine subspecialties of internal medicine
      were chosen for comparison. All data were collected from the Science Citation
      Index Expanded and Journal Citation Reports database. RESULTS: (1) Journal
      numbers in nine subspecialties increased significantly from 1998 to 2010, with an
      average increment of 80.23%, in which cardiac and cardiovascular system diseases
      increased 131.2% rank the first; hematology increased 45% rank the least. (2)
      Impact Factor in subspecialties of infectious disease, cardiac and cardiovascular
      system diseases, gastroenterology and hepatology, hematology, endocrinology and
      metabolism increased significantly (p<0.05), in which gastroenterology and
      hepatology had the largest increase of 65.4%. (3) Journal impact factor of 0-2
      had the largest proportion in all subspecialties. Among the journals with high
      impact factor (IF>6), hematology had the maximum proportion of 10%, nephrology
      and respiratory system disease had the minimum of 4%. Among the journal with low
      impact factor (IF<2), journal in nephrology and allergy had the most (60%), while
      endocrinology and metabolism had the least (40%). There were differences in
      median number of IF among the different subspecialties (p<0.05), in which
      endocrinology and metabolism had the highest, nephrology had the lowest. (4) The
      highest IF had a correlation with journal numbers and total paper numbers in each
      field. CONCLUSION: The IF of internal medicine journals showed an increasingly
      positive trend, in which gastroenterology and hepatology increase the most.
      Hematology had more high IF journals. Endocrinology and metabolism had higher
      average IF. Nephrology remained the lowest position. Numbers of journals and
      total papers were associated with the highest IF.

PMID- 23118976
TI  - Mutation accumulation may only be a minor force in shaping life-history traits,
      even when reproduction is sexual.
AB  - In a previous theoretical study we investigated whether adaptive or non-adaptive
      processes are more important in the evolution of senescence. We built a model
      that combined both processes and found that mutation accumulation is important
      only at those ages where mortality has a negligible impact on fitness. This
      model, however, was limited to haploid organisms. Here we extend our model by
      introducing diploidy and sexual reproduction. We assume that only recessive
      (mutated) homozygotes experience detrimental effects. Our results corroborate our
      previous conclusions, confirming that life histories are largely determined by
      adaptive processes. We also found that the equilibrium frequencies of mutated
      alleles are at higher values than in haploid model, because mutations in
      heterozygotes are hidden for directional selection. Nevertheless, the equilibrium
      frequencies of recessive homozygotes that make mutations visible to selection are
      very similar to the equilibrium frequencies of these alleles in our haploid
      model. Diploidy and sexual reproduction with recombination slows down approaching
      selection-mutation balance.

PMID- 23118974
TI  - Genome-wide association studies of quantitatively measured skin, hair, and eye
      pigmentation in four European populations.
AB  - Pigmentation of the skin, hair, and eyes varies both within and between human
      populations. Identifying the genes and alleles underlying this variation has been
      the goal of many candidate gene and several genome-wide association studies
      (GWAS). Most GWAS for pigmentary traits to date have been based on subjective
      phenotypes using categorical scales. But skin, hair, and eye pigmentation vary
      continuously. Here, we seek to characterize quantitative variation in these
      traits objectively and accurately and to determine their genetic basis. Objective
      and quantitative measures of skin, hair, and eye color were made using
      reflectance or digital spectroscopy in Europeans from Ireland, Poland, Italy, and
      Portugal. A GWAS was conducted for the three quantitative pigmentation phenotypes
      in 176 women across 313,763 SNP loci, and replication of the most significant
      associations was attempted in a sample of 294 European men and women from the
      same countries. We find that the pigmentation phenotypes are highly stratified
      along axes of European genetic differentiation. The country of sampling explains
      approximately 35% of the variation in skin pigmentation, 31% of the variation in
      hair pigmentation, and 40% of the variation in eye pigmentation. All three
      quantitative phenotypes are correlated with each other. In our two-stage
      association study, we reproduce the association of rs1667394 at the OCA2/HERC2
      locus with eye color but we do not identify new genetic determinants of skin and
      hair pigmentation supporting the lack of major genes affecting skin and hair
      color variation within Europe and suggesting that not only careful phenotyping
      but also larger cohorts are required to understand the genetic architecture of
      these complex quantitative traits. Interestingly, we also see that in each of
      these four populations, men are more lightly pigmented in the unexposed skin of
      the inner arm than women, a fact that is underappreciated and may vary across the
      world.

PMID- 23118975
TI  - Crystal structures of lysine-preferred racemases, the non-antibiotic selectable
      markers for transgenic plants.
AB  - Lysine racemase, a pyridoxal 5'-phosphate (PLP)-dependent amino acid racemase
      that catalyzes the interconversion of lysine enantiomers, is valuable to serve as
      a novel non-antibiotic selectable marker in the generation of transgenic plants.
      Here, we have determined the first crystal structure of a lysine racemase (Lyr)
      from Proteus mirabilis BCRC10725, which shows the highest activity toward lysine
      and weaker activity towards arginine. In addition, we establish the first broad
      specificity amino acid racemase (Bar) structure from Pseudomonas putida DSM84,
      which presents not only the highest activity toward lysine but also remarkably
      broad substrate specificity. A complex structure of Bar-lysine is also
      established here. These structures demonstrate the similar fold of alanine
      racemase, which is a head-to-tail homodimer with each protomer containing an N
      terminal (alpha/beta)(8) barrel and a C-terminal beta-stranded domain. The active
      site residues are located at the protomer interface that is a funnel-like cavity
      with two catalytic bases, one from each protomer, and the PLP binding site is at
      the bottom of this cavity. Structural comparisons, site-directed mutagenesis,
      kinetic, and modeling studies identify a conserved arginine and an adjacent
      conserved asparagine that fix the orientation of the PLP O3 atom in both
      structures and assist in the enzyme activity. Furthermore, side chains of two
      residues in alpha-helix 10 have been discovered to point toward the cavity and
      define the substrate specificity. Our results provide a structural foundation for
      the design of racemases with pre-determined substrate specificity and for the
      development of the non-antibiotic selection system in transgenic plants.

PMID- 23118977
TI  - Chronic medical conditions and risk of sepsis.
AB  - BACKGROUND: We sought to determine the associations between baseline chronic
      medical conditions and future risk of sepsis. METHODS: Longitudinal cohort study
      using the 30,239 community-dwelling participants of the REGARDS cohort. We
      determined associations between baseline chronic medical conditions and incident
      sepsis episodes, defined as hospitalization for an infection with the presence of
      infection plus two or more systemic inflammatory response syndrome criteria.
      RESULTS: Over the mean observation time of 4.6 years (February 5, 2003 through
      October 14, 2011), there were 975 incident cases of sepsis. Incident sepsis
      episodes were associated with older age (p<0.001), white race (HR 1.39; 95% CI:
      1.22-1.59), lower education (p<0.001) and income (p<0.001), tobacco use
      (p<0.001), and alcohol use (p = 0.02). Incident sepsis episodes were associated
      with baseline chronic lung disease (adjusted HR 2.43; 95% CI: 2.05-2.86),
      peripheral artery disease (2.16; 1.58-2.95), chronic kidney disease (1.99; 1.73
      2.29), myocardial infarction 1.79 (1.49-2.15), diabetes 1.78 (1.53-2.07), stroke
      1.67 (1.34-2.07), deep vein thrombosis 1.63 (1.29-2.06), coronary artery disease
      1.61 (1.38-1.87), hypertension 1.49 (1.29-1.74), atrial fibrillation 1.48 (1.21
      1.81) and dyslipidemia 1.16 (1.01-1.34). Sepsis risk increased with the number of
      chronic medical conditions (p<0.001). CONCLUSIONS: Individuals with chronic
      medical conditions are at increased risk of future sepsis events.

PMID- 23118978
TI  - Human cord blood derived immature basophils show dual characteristics, expressing
      both basophil and eosinophil associated proteins.
AB  - Basophils are blood cells of low abundance associated with allergy, inflammation
      and parasite infections. To study the transcriptome of mature circulating
      basophils cells were purified from buffy coats by density gradient
      centrifugations and two-step magnetic cell sorting. However, after extensive
      analysis the cells were found to be transcriptionally inactive and almost
      completely lack functional mRNA. In order to obtain transcriptionally active
      immature basophils for analysis of their transcriptome, umbilical cord blood
      cells were therefore cultured in the presence of interleukin (IL)-3 for 9 days
      and basophils were enriched by removing non-basophils using magnetic cell
      sorting. The majority of purified cells demonstrated typical metachromatic
      staining with Alcian blue dye (95%) and expression of surface markers FcepsilonRI
      and CD203c, indicating a pure population of cells with basophil-like phenotype.
      mRNA was extracted from these cells and used to construct a cDNA library with
      approximately 600 000 independent clones. This library served as tool to
      determine the mRNA frequencies for a number of hematopoietic marker proteins. It
      was shown that these cells express basophil/mast cell-specific transcripts, i.e.
      beta-tryptase, serglycin and FcepsilonRI alpha-chain, to a relatively low degree.
      In contrast, the library contained a high number of several eosinophil-associated
      transcripts such as: major basic protein (MBP), charcot leyden crystal (CLC),
      eosinophil cationic protein (ECP), eosinophil derived neurotoxin (EDN) and
      eosinophil peroxidase (EPO). Out of these transcripts, MBP and EPO were the most
      frequently observed, representing 8% and 3.2% of the total mRNA pool,
      respectively. Moreover, in a proteome analysis of cultured basophils we
      identified MBP and EPO as the two most prominent protein bands, suggesting a good
      correlation between protein and mRNA analyses of these cells. The mixed phenotype
      observed for these cells strengthens the conclusion that eosinophils and
      basophils are closely linked during human hematopoietic development. The dual
      phenotype also indicates that other cytokines than IL-3 or cell surface
      interactions are needed to obtain the full basophil specific phenotype in vivo.

PMID- 23118979
TI  - Copeptin, procalcitonin and routine inflammatory markers-predictors of infection
      after stroke.
AB  - BACKGROUND: Early predictors for the development of stroke-associated infection
      may identify patients at high risk and reduce post-stroke infection and
      mortality. METHODS: In 383 prospectively enrolled acute stroke patients we
      assessed time point and type of post-stroke infections (i.e. pneumonia, urinary
      tract infection (UTI) other infection (OI)). Blood samples were collected on
      admission, and days 1, and 3 to assess white blood cells (WBC), monocytes, C
      reactive protein (CRP), procalcitonin (PCT), and copeptin. To determine the
      magnitude of association with the development of infections, odds ratios (OR)
      were calculated for each prognostic blood marker. The discriminatory ability of
      different predictors was assessed, by calculating area under the receiver
      operating characteristic curves (AUC). Prognostic models including the three
      parameters with the best performance were identified. RESULTS: Of 383 patients,
      66 (17.2%) developed an infection after onset of stroke. WBC, CRP, copeptin and
      PCT were all independent predictors of any infection, pneumonia and UTI developed
      at least 24 hours after measurements. The combination of the biomarkers WBC, CRP
      and copeptin (AUC: 0.92) and WBC, CRP and PCT (AUC: 0.90) showed a better
      predictive accuracy concerning the development of pneumonia during
      hospitalization compared to each marker by itself (p-Wald <0.0001). CONCLUSION:
      Among ischemic stroke patients, copeptin, PCT, WBC and CRP measured on admission
      were predictors of infection in general, and specifically for pneumonia and UTI
      within 5 days after stroke. The combination of these biomarkers improved the
      prediction of patients who developed an infection.

PMID- 23118980
TI  - Covalent NEDD8 conjugation increases RCAN1 protein stability and potentiates its
      inhibitory action on calcineurin.
AB  - Similar to ubiquitin, regulatory roles for NEDD8 (neural precursor cell-expressed
      developmentally down-regulated 8) are being clarified during cell growth, signal
      transduction, immune response, and development. However, NEDD8 targets and their
      functional alterations are not well known. Regulator of calcineurin 1
      (RCAN1/DSCR1P1) is located near the Down syndrome critical region on the distal
      part of chromosome 21, and its gene product is an endogenous inhibitor of
      calcineurin signaling. RCAN1 is modified by ubiquitin and consequently undergoes
      proteasomal degradation. Here we report that NEDD8 is conjugated to RCAN1 (RCAN1
      1S) via three lysine residues, K96, K104, and K107. Neddylation enhances RCAN1
      protein stability without affecting its cellular location. In addition, we found
      that neddylation significantly inhibits proteasomal degradation of RCAN1, which
      may underlie the ability of NEDD8 to enhance RCAN1 stability. Furthermore,
      neddylation increases RCAN1 binding to calcineurin, which potentiates its
      inhibitory activity toward downstream NFAT signaling. The present study provides
      a new regulatory mechanism of RCAN1 function and highlights an important role for
      diverse RCAN1-involved cellular physiology.

PMID- 23118981
TI  - DEMO-II trial. Aerobic exercise versus stretching exercise in patients with major
      depression-a randomised clinical trial.
AB  - BACKGROUND: The effect of referring patients from a clinical setting to a
      pragmatic exercise intervention for depressive symptoms, cognitive function, and
      metabolic variables has yet to be determined. METHODS: Outpatients with major
      depression (DSM-IV) were allocated to supervised aerobic or stretching exercise
      groups during a three months period. The primary outcome was the Hamilton
      depression score (HAM-D(17)). Secondary outcomes were cognitive function,
      cardiovascular risk markers, and employment related outcomes. RESULTS: 56
      participants were allocated to the aerobic exercise intervention versus 59
      participants to the stretching exercise group. Post intervention the mean
      difference between groups was -0.78 points on the HAM-D(17) (95% CI -3.2 to 1.6;
      P = .52). At follow-up, the participants in the aerobic exercise group had higher
      maximal oxygen uptake (mean difference 4.4 l/kg/min; 95% CI 1.7 to 7.0; P = .001)
      and visuospatial memory on Rey's Complex Figure Test (mean difference 3.2 points;
      95% CI 0.9 to 5.5; P = .007) and lower blood glucose levels (mean difference 0.2
      mmol/l; 95% CI 0.0 to 0.5; P = .04) and waist circumference (mean difference 2.2
      cm; 95% CI 0.3 to 4.1; P = .02) compared with the stretching exercise group.
      CONCLUSIONS: The results of this trial does not support any antidepressant effect
      of referring patients with major depression to a three months aerobic exercise
      program. Due to lower recruitment than anticipated, the trial was terminated
      prior to reaching the pre-defined sample size of 212 participants; therefore the
      results should be interpreted in that context. However, the DEMO-II trial does
      suggest that an exercise program for patients with depression offer positive
      short-term effects on maximal oxygen uptake, visuospatial memory, fasting glucose
      levels, and waist circumference. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT00695552.

PMID- 23118982
TI  - High resolution size analysis of fetal DNA in the urine of pregnant women by
      paired-end massively parallel sequencing.
AB  - BACKGROUND: Fetal DNA in maternal urine, if present, would be a valuable source
      of fetal genetic material for noninvasive prenatal diagnosis. However, the
      existence of fetal DNA in maternal urine has remained controversial. The issue is
      due to the lack of appropriate technology to robustly detect the potentially
      highly degraded fetal DNA in maternal urine. METHODOLOGY: We have used massively
      parallel paired-end sequencing to investigate cell-free DNA molecules in maternal
      urine. Catheterized urine samples were collected from seven pregnant women during
      the third trimester of pregnancies. We detected fetal DNA by identifying
      sequenced reads that contained fetal-specific alleles of the single nucleotide
      polymorphisms. The sizes of individual urinary DNA fragments were deduced from
      the alignment positions of the paired reads. We measured the fractional fetal DNA
      concentration as well as the size distributions of fetal and maternal DNA in
      maternal urine. PRINCIPAL FINDINGS: Cell-free fetal DNA was detected in five of
      the seven maternal urine samples, with the fractional fetal DNA concentrations
      ranged from 1.92% to 4.73%. Fetal DNA became undetectable in maternal urine after
      delivery. The total urinary cell-free DNA molecules were less intact when
      compared with plasma DNA. Urinary fetal DNA fragments were very short, and the
      most dominant fetal sequences were between 29 bp and 45 bp in length.
      CONCLUSIONS: With the use of massively parallel sequencing, we have confirmed the
      existence of transrenal fetal DNA in maternal urine, and have shown that urinary
      fetal DNA was heavily degraded.

PMID- 23118983
TI  - A delta38 deletion variant of human transketolase as a model of transketolase
      like protein 1 exhibits no enzymatic activity.
AB  - Besides transketolase (TKT), a thiamin-dependent enzyme of the pentose phosphate
      pathway, the human genome encodes for two closely related transketolase-like
      proteins, which share a high sequence identity with TKT. Transketolase-like
      protein 1 (TKTL1) has been implicated in cancerogenesis as its cellular
      expression levels were reported to directly correlate with invasion efficiency of
      cancer cells and patient mortality. It has been proposed that TKTL1 exerts its
      function by catalyzing an unusual enzymatic reaction, a hypothesis that has been
      the subject of recent controversy. The most striking difference between TKTL1 and
      TKT is a deletion of 38 consecutive amino acids in the N-terminal domain of the
      former, which constitute part of the active site in authentic TKT. Our structural
      and sequence analysis suggested that TKTL1 might not possess transketolase
      activity. In order to test this hypothesis in the absence of a recombinant
      expression system for TKTL1 and resilient data on its biochemical properties, we
      have engineered and biochemically characterized a "pseudo-TKTL1" Delta38 deletion
      variant of human TKT (TKTDelta38) as a viable model of TKTL1. Although the
      isolated protein is properly folded under in vitro conditions, both thermal
      stability as well as stability of the TKT-specific homodimeric assembly are
      markedly reduced. Circular dichroism and NMR spectroscopic analysis further
      indicates that TKTDelta38 is unable to bind the thiamin cofactor in a specific
      manner, even at superphysiological concentrations. No transketolase activity of
      TKTDelta38 can be detected for conversion of physiological sugar substrates thus
      arguing against an intrinsically encoded enzymatic function of TKTL1 in tumor
      cell metabolism.

PMID- 23118984
TI  - A T cell-inducing influenza vaccine for the elderly: safety and immunogenicity of
      MVA-NP+M1 in adults aged over 50 years.
AB  - BACKGROUND: Current influenza vaccines have reduced immunogenicity and are of
      uncertain efficacy in older adults. We assessed the safety and immunogenicity of
      MVA-NP+M1, a viral-vectored influenza vaccine designed to boost memory T cell
      responses, in a group of older adults. METHODS: Thirty volunteers (aged 50-85)
      received a single intramuscular injection of MVA-NP+M1 at a dose of 1.5*10(8)
      plaque forming units (pfu). Safety and immunogenicity were assessed over a period
      of one year. The frequency of T cells specific for nucleoprotein (NP) and matrix
      protein 1 (M1) was determined by interferon-gamma (IFN-gamma) ELISpot, and their
      phenotypic and functional properties were characterized by polychromatic flow
      cytometry. In a subset of M1-specific CD8(+) T cells, T cell receptor (TCR) gene
      expression was evaluated using an unbiased molecular approach. RESULTS:
      Vaccination with MVA-NP+M1 was well tolerated. ELISpot responses were boosted
      significantly above baseline following vaccination. Increases were detected in
      both CD4(+) and CD8(+) T cell subsets. Clonality studies indicated that MVA-NP+M1
      expanded pre-existing memory CD8(+) T cells, which displayed a predominant
      CD27(+)CD45RO(+)CD57(-)CCR7(-) phenotype both before and after vaccination.
      CONCLUSIONS: MVA-NP+M1 is safe and immunogenic in older adults. Unlike seasonal
      influenza vaccination, the immune responses generated by MVA-NP+M1 are similar
      between younger and older individuals. A T cell-inducing vaccine such as MVA
      NP+M1 may therefore provide a way to circumvent the immunosenescence that impairs
      routine influenza vaccination. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT00942071.

PMID- 23118985
TI  - The cost of treating advanced non-small cell lung cancer: estimates from the
      chinese experience.
AB  - BACKGROUND: Because of the potentially significant economic burden of healthcare
      costs associated with many diseases, it is critical that regulatory and medical
      insurance organisations collect and utilise data on the cost-effectiveness of
      care provision to make rational policy decisions. However, little is known about
      healthcare costs in China. METHODOLOGY/PRINCIPAL FINDINGS: Based on health
      expenditure data for 253 cases of advanced non-small cell lung cancer (NSCLC)
      registered at the Second Xiangya Hospital of Central South University in China
      between 2006 and 2010, the cost of care provision was analysed. The monthly and
      aggregate annual medical costs were estimated for patients who were in either a
      progression-free state (PFS) or a disease-progression state (DPS). Monthly
      healthcare costs accumulated during the terminal 3 months were collected
      separately. The mean cost of treatment for PFS and DPS patients over one year was
      approximately US$11,566 and $14,519, respectively. The monthly costs for all
      patients were higher initially than in the subsequent months (PFS: $2,490; DPS:
      $2,503). For PFS patients, healthcare expenditures stabilised after the 7th
      month, with a mean monthly medical expenditure of $82.49. For DPS patients,
      expenditures stabilised after the 9th month, and the mean expenditure during the
      9th month was $307.9. Medical care costs in the three successive months prior to
      death were $3,754, $5,829 and $7,372, respectively. CONCLUSIONS/SIGNIFICANCE: The
      economic evaluation of health care technologies is becoming ever more important
      in China, especially in disease areas for which new and expensive therapies are
      being introduced on a regular basis. This is first paper to present empirically
      estimated China-specific costs associated with the treatment of NSCLC. The cost
      estimates are presented in a format that is specifically intended to inform cost
      effectiveness analyses of treatments for NSCLC, and hence, contribute to the more
      efficient allocation of limited healthcare resources in China.

PMID- 23118986
TI  - NOX2beta: A novel splice variant of NOX2 that regulates NADPH oxidase activity in
      macrophages.
AB  - Nox2 oxidase is one isoform in a family of seven NADPH oxidases that generate
      reactive oxygen species (ROS) and thereby contribute to physiological and
      pathological processes including host defense, redox signaling and oxidative
      tissue damage. While alternative mRNA splicing has been shown to influence the
      activity of several Nox-family proteins, functionally relevant splice variants of
      Nox2 have not previously been identified. We immunoscreened several mouse tissues
      and cells for the presence of truncated Nox2 proteins and identified a 30 kDa
      protein in lung, spleen and macrophages. RT-PCR analysis of mRNA from primary and
      immortalised (RAW264.7) mouse macrophages, and from human alveolar macrophages,
      identified a truncated Nox2 transcript which, upon sequence analysis, was found
      to be a product of the 'exon skipping' mode of alternative splicing, lacking
      exons 4-10 of the Nox2 gene. The predicted protein is comparable in size to that
      identified by immunoscreening and contains two transmembrane helices and an
      extended cytosolic C-terminus with binding sites for NADPH and the Nox organiser
      protein p47phox. Importantly, selective siRNA-mediated knockdown of the
      transcript reduced expression of the 30 kDa protein in macrophages, and
      suppressed phorbol ester-stimulated ROS production by 50%. We thus provide the
      first evidence that Nox2 undergoes alternative mRNA splicing to yield a 30 kDa
      protein - herein termed Nox2beta - that regulates NADPH oxidase activity in
      macrophages from mice and humans. The discovery of Nox2beta paves the way for
      future examination of its role in physiological and pathological processes.

PMID- 23118987
TI  - Beaming into the rat world: enabling real-time interaction between rat and human
      each at their own scale.
AB  - Immersive virtual reality (IVR) typically generates the illusion in participants
      that they are in the displayed virtual scene where they can experience and
      interact in events as if they were really happening. Teleoperator (TO) systems
      place people at a remote physical destination embodied as a robotic device, and
      where typically participants have the sensation of being at the destination, with
      the ability to interact with entities there. In this paper, we show how to
      combine IVR and TO to allow a new class of application. The participant in the
      IVR is represented in the destination by a physical robot (TO) and simultaneously
      the remote place and entities within it are represented to the participant in the
      IVR. Hence, the IVR participant has a normal virtual reality experience, but
      where his or her actions and behaviour control the remote robot and can therefore
      have physical consequences. Here, we show how such a system can be deployed to
      allow a human and a rat to operate together, but the human interacting with the
      rat on a human scale, and the rat interacting with the human on the rat scale.
      The human is represented in a rat arena by a small robot that is slaved to the
      human's movements, whereas the tracked rat is represented to the human in the
      virtual reality by a humanoid avatar. We describe the system and also a study
      that was designed to test whether humans can successfully play a game with the
      rat. The results show that the system functioned well and that the humans were
      able to interact with the rat to fulfil the tasks of the game. This system opens
      up the possibility of new applications in the life sciences involving participant
      observation of and interaction with animals but at human scale.

PMID- 23118989
TI  - Insights into the evolutionary features of human neurodegenerative diseases.
AB  - Comparative analyses between human disease and non-disease genes are of great
      interest in understanding human disease gene evolution. However, the progression
      of neurodegenerative diseases (NDD) involving amyloid formation in specific brain
      regions is still unknown. Therefore, in this study, we mainly focused our
      analysis on the evolutionary features of human NDD genes with respect to non
      disease genes. Here, we observed that human NDD genes are evolutionarily
      conserved relative to non-disease genes. To elucidate the conserved nature of NDD
      genes, we incorporated the evolutionary attributes like gene expression level,
      number of regulatory miRNAs, protein connectivity, intrinsic disorder content and
      relative aggregation propensity in our analysis. Our studies demonstrate that NDD
      genes have higher gene expression levels in favor of their lower evolutionary
      rates. Additionally, we observed that NDD genes have higher number of different
      regulatory miRNAs target sites and also have higher interaction partners than the
      non-disease genes. Moreover, miRNA targeted genes are known to have higher
      disorder content. In contrast, our analysis exclusively established that NDD
      genes have lower disorder content. In favor of our analysis, we found that NDD
      gene encoded proteins are enriched with multi interface hubs (party hubs) with
      lower disorder contents. Since, proteins with higher disorder content need to
      adapt special structure to reduce their aggregation propensity, NDD proteins
      found to have elevated relative aggregation propensity (RAP) in support of their
      lower disorder content. Finally, our categorical regression analysis confirmed
      the underlined relative dominance of protein connectivity, 3'UTR length, RAP,
      nature of hubs (singlish/multi interface) and disorder content for such
      evolutionary rates variation between human NDD genes and non-disease genes.

PMID- 23118988
TI  - beta1 integrin-focal adhesion kinase (FAK) signaling modulates retinal ganglion
      cell (RGC) survival.
AB  - Extracellular matrix (ECM) integrity in the central nervous system (CNS) is
      essential for neuronal homeostasis. Signals from the ECM are transmitted to
      neurons through integrins, a family of cell surface receptors that mediate cell
      attachment to ECM. We have previously established a causal link between the
      activation of the matrix metalloproteinase-9 (MMP-9), degradation of laminin in
      the ECM of retinal ganglion cells (RGCs), and RGC death in a mouse model of
      retinal ischemia-reperfusion injury (RIRI). Here we investigated the role of
      laminin-integrin signaling in RGC survival in vitro, and after ischemia in vivo.
      In purified primary rat RGCs, stimulation of the beta1 integrin receptor with
      laminin, or agonist antibodies enhanced RGC survival in correlation with
      activation of beta1 integrin's major downstream regulator, focal adhesion kinase
      (FAK). Furthermore, beta1 integrin binding and FAK activation were required for
      RGCs' survival response to laminin. Finally, in vivo after RIRI, we observed an
      up-regulation of MMP-9, proteolytic degradation of laminin, decreased RGC
      expression of beta1 integrin, FAK and Akt dephosphorylation, and reduced
      expression of the pro-survival molecule bcl-xL in the period preceding RGC
      apoptosis. RGC death was prevented, in the context of laminin degradation, by
      maintaining beta1 integrin activation with agonist antibodies. Thus, disruption
      of homeostatic RGC-laminin interaction and signaling leads to cell death after
      retinal ischemia, and maintaining integrin activation may be a therapeutic
      approach to neuroprotection.

PMID- 23118990
TI  - Effects of an early experience of reward through maternal contact or its denial
      on laterality of protein expression in the developing rat hippocampus.
AB  - Laterality is a basic characteristic of the brain which is detectable early in
      life. Although early experiences affect laterality of the mature brain, there are
      no reports on their immediate neurochemical effects during neonatal life, which
      could provide evidence as to the mechanisms leading to the lateralized brain. In
      order to address this issue, we determined the differential protein expression
      profile of the left and right hippocampus of 13-day-old rat control (CTR) pups,
      as well as following exposure to an early experience involving either receipt
      (RER) or denial (DER) of the expected reward of maternal contact. Proteomic
      analysis was performed by 2-dimensional polyacrylamide gel electrophoresis (PAGE)
      followed by mass spectroscopy. The majority of proteins found to be
      differentially expressed either between the three experimental groups (DER, RER,
      CTR) or between the left and right hemisphere were cytoskeletal (34%), enzymes of
      energy metabolism (32%), and heat shock proteins (17%). In all three groups more
      proteins were up-regulated in the left compared to the right hippocampus.
      Tubulins were found to be most often up-regulated, always in the left
      hippocampus. The differential expression of beta-tubulin, beta-actin,
      dihydropyrimidinase like protein 1, glial fibrillary acidic protein (GFAP) and
      Heat Shock protein 70 revealed by the proteomic analysis was in general confirmed
      by Western blots. Exposure to the early experience affected brain asymmetry: In
      the RER pups the ratio of proteins up-regulated in the left hippocampus to those
      in the right was 1.8, while the respective ratio was 3.6 in the CTR and 3.4 in
      the DER. Our results could contribute to the elucidation of the cellular
      mechanisms mediating the effects of early experiences on the vulnerability for
      psychopathology, since proteins shown in our study to be differentially expressed
      (e.g. tubulins, dihydropyrimidinase like proteins, 14-3-3 protein, GFAP, ATP
      synthase, alpha-internexin) have also been identified in proteomic analyses of
      post-mortem brains from psychiatric patients.

PMID- 23118991
TI  - Association between single nucleotide polymorphisms (SNPs) and toxicity of
      advanced non-small-cell lung cancer patients treated with chemotherapy.
AB  - New therapeutic approaches are being developed based on the findings that several
      genetic abnormalities underlying non-small-cell lung cancer (NSCLC) could
      influence chemosensitivity. In this study, we assessed whether polymorphisms in
      genes of nucleotide excision repair (NER) pathway, including ERCC5, ERCC6,
      MMS19L, CCNH, XPC, RRM1, can affect the tolerability of platinum-based
      chemotherapy in NSCLC patients. We used AllGloTM probe to assess genotyping and
      polymorphisms in 388 stage IIIB and IV NSCLC patients treated with platinum-based
      chemotherapy. MMS19L might be associated with the adverse events of chemotherapy
      in NSCLC, especially for all grade leucopenia (P = 0.020), all grade jaundice (P
      = 0.037) and all grade creatinine increasing (P = 0.013). In terms of grade 3/4
      adverse events, MMS19L was related with total grade 3/4 adverse events (P =
      0.024) and grade 3/4 thrombocytopenia (P = 0.035), while RRM1 was related with
      total grade 3/4 adverse events (P = 0.047) and grade 3/4 vomiting (P = 0.046).
      ERCC5 was related with more infection (P = 0.017). We found that some SNPs in NER
      pathway genes were correlated with toxicity treated with double chemotherapy in
      advanced NSCLC patients, especially for SNPs of MMS19L, RRM1 and ERCC5.

PMID- 23118993
TI  - Associations of different phenotypes of wheezing illness in early childhood with
      environmental variables implicated in the aetiology of asthma.
AB  - RATIONALE: Asthma is a complex heterogeneous disease that has increased in
      prevalence in many industrialised countries. However, the causes of asthma
      inception remain elusive. Consideration of sub-phenotypes of wheezing may reveal
      important clues to aetiological risk factors. METHODS: Longitudinal phenotypes
      capturing population heterogeneity in wheezing reports from birth to 7 years were
      derived using latent class analysis in the Avon Longitudinal Study of Parents and
      Children (ALSPAC). Probability of class membership was used to examine the
      association between five wheezing phenotypes (transient early, prolonged early,
      intermediate-onset, late-onset, persistent) and early life risk factors for
      asthma. RESULTS: Phenotypes had similar patterns and strengths of associations
      with early environmental factors. Comparing transient early with prolonged early
      wheezing showed a similar pattern of association with most exposure variables
      considered in terms of the direction of the effect estimates but with prolonged
      early wheezing tending to have stronger associations than transient early
      wheezing except for parity and day care attendance. CONCLUSIONS: Associations
      with early life risk factors suggested that prolonged early wheeze might be a
      severe form of transient early wheezing. Although differences were found in the
      associations of early life risk factors with individual phenotypes, these did not
      point to novel aetiological pathways. Persistent wheezing phenotype has features
      suggesting overlap of early and late-onset phenotypes.

PMID- 23118992
TI  - Neural correlates of true and false memory in mild cognitive impairment.
AB  - The goal of this research was to investigate the changes in neural processing in
      mild cognitive impairment. We measured phase synchrony, amplitudes, and event
      related potentials in veridical and false memory to determine whether these
      differed in participants with mild cognitive impairment compared with typical,
      age-matched controls. Empirical mode decomposition phase locking analysis was
      used to assess synchrony, which is the first time this analysis technique has
      been applied in a complex cognitive task such as memory processing. The technique
      allowed assessment of changes in frontal and parietal cortex connectivity over
      time during a memory task, without a priori selection of frequency ranges, which
      has been shown previously to influence synchrony detection. Phase synchrony
      differed significantly in its timing and degree between participant groups in the
      theta and alpha frequency ranges. Timing differences suggested greater dependence
      on gist memory in the presence of mild cognitive impairment. The group with mild
      cognitive impairment had significantly more frontal theta phase locking than the
      controls in the absence of a significant behavioural difference in the task,
      providing new evidence for compensatory processing in the former group. Both
      groups showed greater frontal phase locking during false than true memory,
      suggesting increased searching when no actual memory trace was found. Significant
      inter-group differences in frontal alpha phase locking provided support for a
      role for lower and upper alpha oscillations in memory processing. Finally, fronto
      parietal interaction was significantly reduced in the group with mild cognitive
      impairment, supporting the notion that mild cognitive impairment could represent
      an early stage in Alzheimer's disease, which has been described as a
      'disconnection syndrome'.

PMID- 23118994
TI  - The pilin protein FimP from Actinomyces oris: crystal structure and sequence
      analyses.
AB  - The Actinomyces oris type-1 pili are important for the initial formation of
      dental plaque by binding to salivary proteins that adhere to the tooth surface.
      Here we present the X-ray structure of FimP, the protein that is polymerized into
      the type-1 pilus stalk, assisted by a pili-specific sortase. FimP consists of
      three tandem IgG-like domains. The middle and C-terminal domains contain one
      autocatalyzed intramolecular isopeptide bond each, a feature used by Gram
      positive bacteria for stabilization of surface proteins. While the N-terminal
      domain harbours all the residues necessary for forming an isopeptide bond, no
      such bond is observed in the crystal structure of this unpolymerized form of
      FimP. The monomer is further stabilized by one disulfide bond each in the N- and
      C-terminal domains as well as by a metal-coordinated loop protruding from the C
      terminal domain. A lysine, predicted to be crucial for FimP polymerization by
      covalent attachment to a threonine from another subunit, is located at the rim of
      a groove lined with conserved residues. The groove may function as a docking site
      for the sortase-FimP complex. We also present sequence analyses performed on the
      genes encoding FimP as well as the related FimA, obtained from clinical isolates.

PMID- 23118995
TI  - Calcium-activated-calcineurin reduces the In vitro and In vivo sensitivity of
      fluconazole to Candida albicans via Rta2p.
AB  - Due to the emergence of drug-resistance, first-line therapy with fluconazole
      (FLC) increasingly resulted in clinical failure for the treatment of candidemia.
      Our previous studies found that in vitro RTA2 was involved in the calcineurin
      mediated resistance to FLC in C. albicans. In this study, we found that calcium
      activated-calcineurin significantly reduced the in vitro sensitivity of C.
      albicans to FLC by blocking the impairment of FLC to the plasma membrane via
      Rta2p. Furthermore, we found that RTA2 itself was not involved in C. albicans
      virulence, but the disruption of RTA2 dramatically increased the therapeutic
      efficacy of FLC in a murine model of systemic candidiasis. Conversely, both re
      introduction of one RTA2 allele and ectopic expression of RTA2 significantly
      reduced FLC efficacy in a mammalian host. Finally, we found that calcium
      activated-calcineurin, through its target Rta2p, dramatically reduced the
      efficacy of FLC against candidemia. Given the critical roles of Rta2p in
      controlling the efficacy of FLC, Rta2p can be a potential drug target for
      antifungal therapies.

PMID- 23118996
TI  - Contrast-enhanced ultrasound in the diagnosis of gallbladder diseases: a multi
      center experience.
AB  - OBJECTIVE: To assess the usefulness of contrast-enhanced ultrasound (CEUS) in
      differentiating malignant from benign gallbladder (GB) diseases. METHODS: This
      study had institutional review board approval. 192 patients with GB diseases from
      9 university hospitals were studied. After intravenous bonus injection of a
      phospholipid-stabilized shell microbubble contrast agent, lesions were scanned
      with low acoustic power CEUS. A multiple logistic regression analysis was
      performed to identify diagnostic clues from 17 independent variables that enabled
      differentiation between malignant and benign GB diseases. Receiver operating
      characteristic (ROC) curve analysis was performed. RESULTS: Among the 17
      independent variables, multiple logistic regression analysis showed that the
      following 4 independent variables were associated with the benign nature of the
      GB diseases, including the patient age, intralesional blood vessel depicted on
      CEUS, contrast washout time, and wall intactness depicted on CEUS (all P<0.05).
      ROC analysis showed that the patient age, intralesional vessels on CEUS, and the
      intactness of the GB wall depicted on CEUS yielded an area under the ROC curve
      (Az) greater than 0.8 in each and Az for the combination of the 4 significant
      independent variables was 0.915 [95% confidence interval (CI): 0.857-0.974]. The
      corresponding Az, sensitivity, and specificity for the age were 0.805 (95% CI:
      0.746-0.863), 92.2%%, and 59.6%; for the intralesional vessels on CEUS were 0.813
      (95% CI: 0.751-0.875), 59.8%, and 98.0%; and for the GB wall intactness were
      0.857 (95% CI: 0.786-0.928), 78.4%, and 92.9%. The cut-off values for benign GB
      diseases were patient age <53.5 yrs, dotted intralesional vessels on CEUS and
      intact GB wall on CEUS. CONCLUSION: CEUS is valuable in differentiating malignant
      from benign GB diseases. Branched or linear intralesional vessels and destruction
      of GB wall on CEUS are the CEUS features highly suggestive of GB malignancy and
      the patient age >53.5 yrs is also a clue for GB malignancy.

PMID- 23118998
TI  - Brown lemurs (Eulemur fulvus) can master the qualitative version of the reverse
      reward contingency.
AB  - Behavioral flexibility that requires behavioral inhibition has important fitness
      consequences. One task commonly used to assess behavioral inhibition is the
      reverse-reward task in which the subject is rewarded by the non selected items.
      Lemurs were tested for their ability to solve the qualitative version of the
      reverse-reward task with the choice between identical quantities of different
      food items instead of different quantities of the same food. Two of four subjects
      mastered the task without a correction procedure and were able to generalize the
      acquired rule to novel combinations of food. One of the two subjects competent on
      the quality version of the task could transfer this ability to different
      quantities of the same food. Our results are compared to lemurs' performances
      when tested under the quantitative version in a previous study and those of
      capuchin monkeys tested under a similar paradigm. The whole results suggest that
      the qualitative version of the reverse-reward task may be easier to master than
      its quantitative counterpart and that lemurs perform better than capuchin monkeys
      as they were able to later transfer the learning rule to the quantitative version
      of the task.

PMID- 23118997
TI  - Epidemiology of patients hospitalized for ocular trauma in the Chaoshan region of
      China, 2001-2010.
AB  - BACKGROUND: The burden and pattern of ocular trauma in China are poorly known and
      not well studied. We aimed at studying the epidemiological characteristics of
      patients hospitalized for ocular trauma at major ophthalmology departments in the
      largest industrial base of plastic toys in China. METHODS: A retrospective study
      of ocular trauma cases admitted to 3 tertiary hospitals in China from 1st January
      2001 to 31st December 2010 was performed. RESULTS: The study included a total of
      3,644 injured eyes from 3,559 patients over the 10-year period: 2,008 (55.1%)
      open-globe injuries, 1,580 (43.4%) closed-globe injuries, 41 (1.1%) chemical
      injuries, 15 (0.4%) thermal injuries and 678 (18.6%) ocular adnexal injuries. The
      mean age of the patients was 29.0+/-16.8 years with a male-to-female ratio of
      5.2?1 (P = 0.007). The most frequent types of injury were work-related injuries
      (1,656, 46.5%) and home-related injuries (715, 20.1%). The majority of injuries
      in males (56.2%) and females (36.0%) occurred in the 15-44 age group and 0-14 age
      group, respectively. The final visual acuity correlated with the initial visual
      acuity (Spearman's correlation coefficient = 0.659; P<0.001). The Ocular Trauma
      Score also correlated with the final visual acuity (Spearman's correlation
      coefficient = 0.655; P<0.001). CONCLUSIONS: This analysis provides an
      epidemiological study of patients who were hospitalized for ocular trauma.
      Preventive efforts are important for both work-related and home-related eye
      injuries.

PMID- 23118999
TI  - Galectin-9 ameliorates Con A-induced hepatitis by inducing CD4(+)CD25(low/int)
      effector T-Cell apoptosis and increasing regulatory T cell number.
AB  - BACKGROUND: T cell-mediated liver damage is a key event in the pathogenesis of
      many chronic human liver diseases, such as liver transplant rejection, primary
      biliary cirrhosis, and sclerosing cholangitis. We and other groups have
      previously reported that galectin-9, one of the beta-galactoside binding animal
      lectins, might be potentially useful in the treatment of T cell-mediated
      diseases. To evaluate the direct effect of galectin-9 on hepatitis induced by
      concanavalin A (Con A) administration in mice and to clarify the mechanisms
      involved, we administered galectin-9 into mice, and evaluated its therapeutic
      effect on Con A-induced hepatitis. METHODOLOGY/PRINCIPAL FINDINGS: Galectin-9 was
      administrated i.v. to Balb/c mice 30 min before Con A injection. Compared with no
      treatment, galectin-9 pretreatment significantly reduced serum ALT and AST levels
      and improved liver histopathology, suggesting an ameliorated hepatitis. This
      therapeutic effect was not only attributable to a blunted Th1 immune response,
      but also to an increased number in regulatory T cells, as reflected in a
      significantly increased apoptosis of CD4(+)CD25(low/int) effector T cells and in
      reduced proinflammatory cytokine levels. CONCLUSION/SIGNIFICANCE: Our findings
      constitute the first preclinical data indicating that interfering with TIM
      3/galectin-9 signaling in vivo could ameliorate Con A-induced hepatitis. This
      strategy may represent a new therapeutic approach in treating human diseases
      involving T cell activation.

PMID- 23119000
TI  - Noninvasive optical measurement of cerebral blood flow in mice using molecular
      dynamics analysis of indocyanine green.
AB  - In preclinical studies of ischemic brain disorders, it is crucial to measure
      cerebral blood flow (CBF); however, this requires radiological techniques with
      heavy instrumentation or invasive procedures. Here, we propose a noninvasive and
      easy-to-use optical imaging technique for measuring CBF in experimental small
      animals. Mice were injected with indocyanine green (ICG) via tail-vein
      catheterization. Time-series near-infrared fluorescence signals excited by 760 nm
      light-emitting diodes were imaged overhead by a charge-coupled device coupled
      with an 830 nm bandpass-filter. We calculated four CBF parameters including
      arrival time, rising time and mean transit time of a bolus and blood flow index
      based on time and intensity information of ICG fluorescence dynamics. CBF maps
      were generated using the parameters to estimate the status of CBF, and they
      dominantly represented intracerebral blood flows in mice even in the presence of
      an intact skull and scalp. We demonstrated that this noninvasive optical imaging
      technique successfully detected reduced local CBF during middle cerebral artery
      occlusion. We further showed that the proposed method is sufficiently sensitive
      to detect the differences between CBF status in mice anesthetized with either
      isoflurane or ketamine-xylazine, and monitor the dynamic changes in CBF after
      reperfusion during transient middle cerebral artery occlusion. The near-infrared
      optical imaging of ICG fluorescence combined with a time-series analysis of the
      molecular dynamics can be a useful noninvasive tool for preclinical studies of
      brain ischemia.

PMID- 23119001
TI  - Repeated abortion affects subsequent pregnancy outcomes in BALB/c mice.
AB  - AIM: In this study, we aimed to establish a mouse model of repeated medical
      termination of pregnancy in order to determine subsequent outcomes. METHODS: A
      model of mifepristone (RU 486)-induced medical abortion was established in BALB/c
      mice to facilitate the investigation of the impact of medical abortion on
      subsequent pregnancies, including litter sizes and newborn birth weights.
      Pregnant mice were sacrificed to examine midterm pregnancy status, investigate
      the frequency of fetal resorption, and measure placental function gene expression
      by real-time PCR and immunohistochemistry. Offspring liver mRNA was harvested for
      real-time PCR to determine gene expression and assess the effects of abortion on
      offspring development. RESULTS: Mice subjected to 2 previous medical abortions
      experienced spontaneous abortions in subsequent pregnancies. Medical abortion
      caused reduced reproductive capacity and affected placental dysfunction, with
      reduced expression of tissue factor (TF) and genes encoding proteins involved in
      metabolic functions relevant to pregnancy, such as 11beta-hydroxysteroid
      dehydrogenase 1/2 (11beta-HSD1/2) and glucocorticoid receptor (GR). Reduced
      expression was also observed for platelet endothelial cell adhesion molecule-1
      (CD31) and vascular endothelial growth factor (VEGF). In offspring from
      subsequent pregnancies, genes involved in lipid metabolism, which may enhance key
      lipid transcription factors, such as PPARA and PPARG, as well as GR/11beta-HSD1,
      were downregulated in the liver. In addition, the sperm motility of the F1 males
      reduced. CONCLUSION: Repeated medical abortion impaired the reproductive function
      of female mice, significantly affecting the outcomes of subsequent pregnancies.
      The impact of repeated abortions on the offspring of subsequent pregnancies was
      also noteworthy and deserves further exploration. Thus, this model provides a
      useful means to study the mechanisms underlying the above phenomena, which will
      ultimately benefit the health of women and their children.

PMID- 23119002
TI  - Comparison of the kinetics of maturation of phagosomes containing apoptotic cells
      and IgG-opsonized particles.
AB  - Defective clearance of apoptotic cells has emerged as an important contributing
      factor to the pathogenesis of many diseases. Although many efforts have been made
      to understand the machinery involved in the recognition between phagocytes and
      potential targets, little is known about the intracellular transport of
      phagosomes containing apoptotic cells within mammalian cells. We have, therefore,
      performed a detailed study on the maturation of phagosomes containing apoptotic
      cells in a non-professional phagocytic cell line. This process was compared with
      the maturation of IgG-opsonized particles, which are internalized via the Fcgamma
      receptor (Fcgamma-R), one of the best characterized phagocytic receptor, in the
      same cell line stably expressing the Fcgamma-RIIA. By comparing markers from
      different stages of phagosome maturation, we have found that phagosomes carrying
      apoptotic particles reach the lysosomes with a delay compared to those containing
      IgG-opsonized particles. Enrichment of the apoptotic particles in
      phosphatidylserine (PS) neither changed the kinetics of their engulfment nor the
      maturation process of the phagosome.

PMID- 23119003
TI  - Upper and lower urinary tract outcomes in adult myelomeningocele patients: a
      systematic review.
AB  - BACKGROUND: The introduction of sophisticated treatment of bladder dysfunction
      and hydrocephalus allows the majority of SB patients to survive into adulthood.
      However, no systematic review on urological outcome in adult SB patients is
      available and no follow-up schemes exist. OBJECTIVES: To systematically summarize
      the evidence on outcome of urinary tract functioning in adult SB patients.
      METHODS: A literature search in PubMed and Embase databases was done. Only papers
      published in the last 25 years describing patients with open SB with a mean age
      >18 years were included. We focused on finding differences in the treatment
      strategies, e.g., clean intermittent catheterization and antimuscarinic drugs
      versus early urinary diversion, with regard to long-term renal and bladder
      outcomes. RESULTS: A total of 13 articles and 5 meeting abstracts on urinary
      tract status of adult SB patients were found describing a total of 1564 patients
      with a mean age of 26.1 years (range 3-74 years, with a few patients <18 years).
      All were retrospective cohort studies with relatively small and heterogeneous
      samples with inconsistent reporting of outcome; this precluded the pooling of
      data and meta-analysis. Total continence was achieved in 449/1192 (37.7%; range 8
      85%) patients. Neurological level of the lesion and hydrocephalus were associated
      with incontinence. Renal function was studied in 1128 adult patients. In 290/1128
      (25.7%; range 3-81.8%) patients some degree of renal damage was found and end
      stage renal disease was seen in 12/958 (1.3%) patients. Detrusor-sphincter
      dyssynergy and detrusor-overactivity acted as adverse prognostic factors for the
      development of renal damage. CONCLUSIONS: These findings should outline follow-up
      schedules for SB patients, which do not yet exist. Since renal and bladder
      deterioration continues beyond adolescence, follow-up of these individuals is
      needed. We recommend standardization in reporting the outcome of urinary tract
      function in adult SB patients.

PMID- 23119005
TI  - HLA and celiac disease susceptibility: new genetic factors bring open questions
      about the HLA influence and gene-dosage effects.
AB  - Celiac disease (CD) is a chronic inflammatory disorder triggered after gluten
      ingestion in genetically susceptible individuals. The major genetic determinants
      are HLA-DQA1*05 and HLA-DQB1*02, which encode the DQ2 heterodimer. These alleles
      are commonly inherited in cis with DRB1*03?01, which is associated with numerous
      immune-related disorders, in some cases contributing with a different amount of
      risk depending on the haplotype context. We aimed at investigating those possible
      differences involving DRB1*03?01-carrying haplotypes in CD susceptibility. A
      family (274 trios) and a case-control sample (369 CD cases/461 controls) were
      analyzed. DRB1*03?01-carrying individuals were classified according to the
      haplotype present (ancestral haplotype (AH) 8.1, AH 18.2 or non-conserved
      haplotype) after genotyping of HLA-DRB1, -DQA1, -DQB1, -B8, TNF -308, TNF -376
      and the TNFa and TNFb microsatellites. We observe that the AH 8.1 confers higher
      risk than the remaining DRB1*03?01-carrying haplotypes, and this effect only
      involves individuals possessing a single copy of DQB1*02. CD risk for these
      individuals is similar to the one conferred by inherit DQA1*05 and DQB1*02 in
      trans. It seems that an additional CD susceptibility factor is present in the AH
      8.1 but not in other DRB1*03?01-carrying haplotypes. This factor could be shared
      with individuals possessing DQ2.5 trans, according to the similar risk observed
      in those two groups of individuals.

PMID- 23119004
TI  - Targeting 3-phosphoinoside-dependent kinase-1 to inhibit insulin-like growth
      factor-I induced AKT and p70 S6 kinase activation in breast cancer cells.
AB  - Binding of IGF to IGF-IR activates PI3K to generate PIP3 which in turn recruits
      and activates proteins that contain a pleckstrin homology (PH) domain, including
      AKT and PDK1. PDK1 is highly expressed in breast tumor samples and breast cancer
      cell lines. Here we demonstrate that targeting PDK1 with the potent and selective
      PDK1 inhibitor PF-5177624 in the IGF-PI3K pathway blocks breast cancer cell
      proliferation and transformation. Breast cancer cell lines MCF7 and T47D,
      representing the luminal ER positive subtype and harboring PIK3CA mutations, were
      most responsive to IGF-I induction resulting in upregulated AKT and p70S6K
      phosphorylation via PDK1 activation. PF-5177624 downregulated AKT and p70S6K
      phosphorylation, blocked cell cycle progression, and decreased cell proliferation
      and transformation to block IGFR-I induced activation in breast cancer cells.
      These results may provide insight into clinical strategies for developing an IGFR
      I inhibitor and/or a PDK1 inhibitor in luminal breast cancer patients.

PMID- 23119006
TI  - Widespread triploidy in Western North American aspen (Populus tremuloides).
AB  - We document high rates of triploidy in aspen (Populus tremuloides) across the
      western USA (up to 69% of genets), and ask whether the incidence of triploidy
      across the species range corresponds with latitude, glacial history (as has been
      documented in other species), climate, or regional variance in clone size. Using
      a combination of microsatellite genotyping, flow cytometry, and cytology, we
      demonstrate that triploidy is highest in unglaciated, drought-prone regions of
      North America, where the largest clone sizes have been reported for this species.
      While we cannot completely rule out a low incidence of undetected aneuploidy,
      tetraploidy or duplicated loci, our evidence suggests that these phenomena are
      unlikely to be significant contributors to our observed patterns. We suggest that
      the distribution of triploid aspen is due to a positive synergy between triploidy
      and ecological factors driving clonality. Although triploids are expected to have
      low fertility, they are hypothesized to be an evolutionary link to sexual
      tetraploidy. Thus, interactions between clonality and polyploidy may be a broadly
      important component of geographic speciation patterns in perennial plants.
      Further, cytotypes are expected to show physiological and structural differences
      which may influence susceptibility to ecological factors such as drought, and we
      suggest that cytotype may be a significant and previously overlooked factor in
      recent patterns of high aspen mortality in the southwestern portion of the
      species range. Finally, triploidy should be carefully considered as a source of
      variance in genomic and ecological studies of aspen, particularly in western U.S.
      landscapes.

PMID- 23119009
TI  - High bone sialoprotein (BSP) expression correlates with increased tumor grade and
      predicts a poorer prognosis of high-grade glioma patients.
AB  - OBJECTIVES: To investigate the expression and prognostic value of bone
      sialoprotein (BSP) in glioma patients. METHODS: We determined the expression of
      BSP using real-time RT-PCR and immunohistochemistry in tissue microarrays
      containing 15 normal brain and 270 glioma samples. Cumulative survival was
      calculated by the Kaplan-Meier method and analyzed by the log-rank test.
      Univariate and multivariate analyses were performed by the stepwise forward Cox
      regression model. RESULTS: Both BSP mRNA and protein levels were significantly
      elevated in high-grade glioma tissues compared with those of normal brain and low
      grade glioma tissues, and BSP expression positively correlated with tumor grade
      (P<0.001). Univariate and multivariate analysis showed high BSP expression was an
      independent prognostic factor for a shorter progression-free survival (PFS) and
      overall survival (OS) in both grade III and grade IV glioma patients [hazard
      ratio (HR) = 2.549 and 3.154 for grade III glioma, and HR = 1.637 and 1.574 for
      grade IV glioma, respectively]. Patients with low BSP expression had a
      significantly longer median OS and PFS than those with high BSP expression. Small
      extent of resection and lineage of astrocyte served as independent risk factors
      of both shorter PFS and OS in grade III glioma patients; GBM patients without
      O(6)-methylguanine (O(6)-meG) DNA methyltransferase (MGMT) methylation and
      Karnofsky performance score (KPS) less than 70 points were related to poor
      prognosis. Lack of radiotherapy related to shorter OS but not affect PFS in both
      grade III and grade IV glioma patients. CONCLUSION: High BSP expression occurs in
      a significant subset of high-grade glioma patients and predicts a poorer outcome.
      The study identifies a potentially useful molecular marker for the categorization
      and targeted therapy of gliomas.

PMID- 23119008
TI  - Short and long term measures of anxiety exhibit opposite results.
AB  - Animal models of human diseases of the central nervous system, generalized
      anxiety disorder included, are essential for the study of the brain-behavior
      interface and obligatory for drug development; yet, these models fail to yield
      new insights and efficacious drugs. By increasing testing duration hundredfold
      and arena size tenfold, and comparing the behavior of the common animal model to
      that of wild mice, we raise concerns that chronic anxiety might have been
      measured at the wrong time, for the wrong duration, and in the wrong animal.
      Furthermore, the mice start the experimental session with a short period of
      transient adaptation to the novel environment (habituation period) and a long
      period reflecting the respective trait of the mice. Using common measures of
      anxiety reveals that mice exhibit opposite results during these periods
      suggesting that chronic anxiety should be measured during the post-habituation
      period. We recommend tools for measuring the transient period, and provide
      suggestions for characterizing the post habituation period.

PMID- 23119007
TI  - The somatostatin analogue octreotide inhibits growth of small intestine
      neuroendocrine tumour cells.
AB  - Octreotide is a widely used synthetic somatostatin analogue that significantly
      improves the management of neuroendocrine tumours (NETs). Octreotide acts through
      somatostatin receptors (SSTRs). However, the molecular mechanisms leading to
      successful disease control or symptom management, especially when SSTRs levels
      are low, are largely unknown. We provide novel insights into how octreotide
      controls NET cells. CNDT2.5 cells were treated from 1 day up to 16 months with
      octreotide and then were profiled using Affymetrix microarray analysis.
      Quantitative real-time PCR and western blot analyses were used to validate
      microarray profiling in silico data. WST-1 cell proliferation assay was applied
      to evaluate cell growth of CNDT2.5 cells in the presence or absence of 1 uM
      octreotide at different time points. Moreover, laser capture microdissected
      tumour cells and paraffin embedded tissue slides from SI-NETs at different stages
      of disease were used to identify transcriptional and translational expression.
      Microarrays analyses did not reveal relevant changes in SSTR expression levels.
      Unexpectedly, six novel genes were found to be upregulated by octreotide: annexin
      A1 (ANXA1), rho GTPase-activating protein 18 (ARHGAP18), epithelial membrane
      protein 1 (EMP1), growth/differentiation factor 15 (GDF15), TGF-beta type II
      receptor (TGFBR2) and tumour necrosis factor (ligand) superfamily member 15
      (TNFSF15). Furthermore, these novel genes were expressed in tumour tissues at
      transcript and protein levels. We suggest that octreotide may use a potential
      novel framework to exert its beneficial effect as a drug and to convey its action
      on neuroendocrine cells. Thus, six novel genes may regulate cell growth and
      differentiation in normal and tumour neuroendocrine cells and have a role in a
      novel octreotide mechanism system.

PMID- 23119010
TI  - Association of chronic kidney disease and peripheral artery disease with
      inappropriate left ventricular mass.
AB  - Inappropriate left ventricular mass index (LVM) may develop as a response to
      particular hemodynamic and metabolic alterations. Inappropriate LVM and
      peripheral artery disease (PAD) characterized by abnormally low or high ankle
      brachial index (ABI) are common in chronic kidney disease (CKD) patients, in whom
      there may be a close and cause-effect relationship. The aim of this study is to
      assess whether CKD and abnormal ABI has an independent and additive association
      with inappropriate LVM. A total of 1110 patients were included in the study.
      Inappropriate LVM was defined as observed LVM more than 28% of the predicted
      value. The ABI was measured using an ABI-form device. PAD was defined as ABI <0.9
      or >1.3 in either leg. Multivariate analysis showed that patients with estimated
      glomerular filtration rate (eGFR) <45 ml/min/1.73 m(2) (odds ratio [OR], 1.644; P
      = 0.011) and PAD (OR, 2.082; P = 0.002) were independently associated with
      inappropriate LVM. The interaction between eGFR <45 ml/min/1.73 m(2) and PAD on
      inappropriate LVM was statistically significant (P = 0.044). Besides, eGFR<45
      ml/min/1.73 m(2) (change in observed/predicted LVM, 19.949; P<0.001) and PAD
      (change in observed/predicted LVM, 11.818; P = 0.003) were also significantly
      associated with observed/predicted LVM. Our findings show that eGFR <45
      ml/min/1.73 m(2) and PAD are independently and additively associated with
      inappropriate LVM and observed/predicted LVM. Assessments of eGFR and ABI may be
      useful in identifying patients with inappropriate LVM.

PMID- 23119011
TI  - Structure-based engineering increased the catalytic turnover rate of a novel
      phenazine prenyltransferase.
AB  - Prenyltransferases (PTs) catalyze the regioselective transfer of prenyl moieties
      onto aromatic substrates in biosynthetic pathways of microbial secondary
      metabolites. Therefore, these enzymes contribute to the chemical diversity of
      natural products. Prenylation is frequently essential for the pharmacological
      properties of these metabolites, including their antibiotic and antitumor
      activities. Recently, the first phenazine PTs, termed EpzP and PpzP, were
      isolated and biochemically characterized. The two enzymes play a central role in
      the biosynthesis of endophenazines by catalyzing the regiospecific prenylation of
      5,10-dihydrophenazine-1-carboxylic acid (dhPCA) in the secondary metabolism of
      two different Streptomyces strains. Here we report crystal structures of EpzP in
      its unliganded state as well as bound to S-thiolodiphosphate (SPP), thus defining
      the first three-dimensional structures for any phenazine PT. A model of a ternary
      complex resulted from in silico modeling of dhPCA and site-directed mutagenesis.
      The structural analysis provides detailed insight into the likely mechanism of
      phenazine prenylation. The catalytic mechanism suggested by the structure
      identifies amino acids that are required for catalysis. Inspection of the
      structures and the model of the ternary complex furthermore allowed us to
      rationally engineer EpzP variants with up to 14-fold higher catalytic reaction
      rate compared to the wild-type enzyme. This study therefore provides a solid
      foundation for additional enzyme modifications that should result in efficient,
      tailor-made biocatalysts for phenazines production.

PMID- 23119013
TI  - Shift of bacterial community in synanthropic mite Tyrophagus putrescentiae
      induced by Fusarium fungal diet.
AB  - BACKGROUND: Tyrophagus putrescentiae (Acari: Astigmata) and Fusarium sp. co-occur
      in poorly managed grain. In a laboratory experiment, mite grazing resulted in
      significant reduction of fungal mycelium on cultivation plates. The destruction
      of mycelium appeared to be a result of an interaction between the mites, fungi
      and associated bacteria. METHODOLOGY AND PRINCIPAL FINDINGS: A laboratory
      experiment was performed to simulate a situation of grain multiinfested by mites
      and Fusarium fungi. Changes of mite-associated bacterial community in T.
      putrescentiae were described in 3 habitats: (i) T. putrescentiae mites from a
      rearing diet prior to their transfer to fungal diet; (ii) fungal mycelium before
      mite introduction; (iii) mites after 7 day diet of each Fusarium avenaceum, F.
      culmorum, F. poae and F. verticillioides. Bacterial communities were
      characterized by 16 S rRNA gene sequencing. In total, 157 nearly full-length 16 S
      rRNA gene sequences from 9 samples representing selected habitats were analyzed.
      In the mites, the shift from rearing to fungal diet caused changes in mite
      associated bacterial community. A diverse bacterial community was associated with
      mites feeding on F. avenaceum, while feeding on the other three Fusarium spp. led
      to selection of a community dominated by Bacillaceae. CONCLUSIONS/SIGNIFICANCE:
      The work demonstrated changes of bacterial community associated with T.
      putrescentiae after shift to fungal diets suggesting selection for Bacillaceae
      species known as chitinase producers, which might participate in the fungal
      mycelium hydrolysis.

PMID- 23119012
TI  - TNAP and EHD1 are over-expressed in bovine brain capillary endothelial cells
      after the re-induction of blood-brain barrier properties.
AB  - Although the physiological properties of the blood-brain barrier (BBB) are
      relatively well known, the phenotype of the component brain capillary endothelial
      cells (BCECs) has yet to be described in detail. Likewise, the molecular
      mechanisms that govern the establishment and maintenance of the BBB are largely
      unknown. Proteomics can be used to assess quantitative changes in protein levels
      and identify proteins involved in the molecular pathways responsible for cellular
      differentiation. Using the well-established in vitro BBB model developed in our
      laboratory, we performed a differential nano-LC MALDI-TOF/TOF-MS study of Triton
      X-100-soluble protein species from bovine BCECs displaying either limited BBB
      functions or BBB functions re-induced by glial cells. Due to the heterogeneity of
      the crude extract, we increased identification yields by applying a repeatable,
      reproducible fractionation process based on the proteins' relative
      hydrophobicity. We present proteomic and biochemical evidence to show that tissue
      non-specific alkaline phosphatase (TNAP) and Eps15 homology domain-containing
      protein 1(EDH1) are over-expressed by bovine BCECs after the re-induction of BBB
      properties. We discuss the impact of these findings on current knowledge of
      endothelial and BBB permeability.

PMID- 23119014
TI  - Dual-phase PET-CT to differentiate [18F]Fluoromethylcholine uptake in reactive
      and malignant lymph nodes in patients with prostate cancer.
AB  - PURPOSE: To investigate whether time-trends of enhanced
      [(18)F]Fluoromethylcholine ([(18)F]FCH) in lymph nodes (LN) of prostate cancer
      (PCa) patients can help to discriminate reactive from malignant ones, and whether
      single time point standardized uptake value (SUV) measurements also suffice.
      PROCEDURES: 25 PCa patients with inguinal (presumed benign) and enlarged pelvic
      LN (presumed malignant) showing enhanced [(18)F]FCH uptake at dual-phase PET-CT
      were analyzed. Associations between LN status (benign versus malignant) and
      SUV(max) and SUV(meanA50), determined at 2 min (early) and 30 min (late) post
      injection, were assessed. We considered two time-trends of [(18)F]FCH uptake:
      type A (SUV early > SUV late) and type B (SUV late >= SUV early). Histopathology
      and/or follow-up were used to confirm the assumption that LN with type A pattern
      are benign, and LN with type B pattern malignant. RESULTS: Analysis of 54 nodes
      showed that LN status, time-trends, and 'late' (30 min p.i.) SUV(max) and
      SUV(meanA50) parameters were strongly associated (P<0.0001). SUV(max) relative
      difference was the best LN status predictor. All but one inguinal LN showed a
      decreasing [(18)F]FCH uptake over time (pattern A), while 95% of the pelvic nodes
      presented a stable or increasing uptake (pattern B) type. CONCLUSIONS: Time
      trends of enhanced [(18)F]FCH uptake can help to characterize lymph nodes in
      prostate cancer patients. Single time-point SUV measurements, 30 min p.i., may be
      a reasonable alternative for predicting benign versus malignant status of lymph
      nodes, but this remains to be validated in non-enlarged pelvic lymph nodes.

PMID- 23119015
TI  - Five-year olds, but not chimpanzees, attempt to manage their reputations.
AB  - Virtually all theories of the evolution of cooperation require that cooperators
      find ways to interact with one another selectively, to the exclusion of cheaters.
      This means that individuals must make reputational judgments about others as
      cooperators, based on either direct or indirect evidence. Humans, and possibly
      other species, add another component to the process: they know that they are
      being judged by others, and so they adjust their behavior in order to affect
      those judgments - so-called impression management. Here, we show for the first
      time that already preschool children engage in such behavior. In an experimental
      study, 5-year-old human children share more and steal less when they are being
      watched by a peer than when they are alone. In contrast, chimpanzees behave the
      same whether they are being watched by a groupmate or not. This species
      difference suggests that humans' concern for their own self-reputation, and their
      tendency to manage the impression they are making on others, may be unique to
      humans among primates.

PMID- 23119016
TI  - Combined minimally invasive percutaneous nephrolithotomy and retrograde
      intrarenal surgery for staghorn calculi in patients with solitary kidney.
AB  - BACKGROUND: To present our experience with simultaneous combined minimally
      invasive percutaneous nephrolithotomy (MPCNL) and retrograde intrarenal surgery
      (RIRS) to manage patients with staghorn calculi in solitary kidney, and evaluate
      the safety, efficiency and feasibility of this approach. METHODOLOGY/PRINCIPAL
      FINDINGS: The study included 20 patients with staghorn calculi in solitary
      kidney. Demographic characteristics, stone location and surface area were
      recorded. After informed consent, the patients underwent one stage MPCNL firstly.
      Combined second stage MPCNL and RIRS simultaneously were performed at
      postoperative 5-7 days. Operative parameters, stone-free rate (SFR), stone
      analyses and complications were evaluated. Serum creatinine (Scr), glomerular
      filtration rate (GFR) and chronic kidney disease (CKD) were measured
      preoperatively, postoperatively at 1 month, and each follow-up visit. All
      patients had staghorn stones involving multiple calyces. The mean stone burden
      was 1099.9 +/- 843.95 mm(2). All patients had only one percutaneous access tract.
      The mean whole operative duration was 154.37 +/- 32.45 min. The mean blood loss
      was 64 (12-140) ml. The final SFR was 90%. During the 1-month follow-up study
      period, four patients improved in CKD stage. Two patients who had CKD (stage 5)
      still needed dialysis postoperatively. Mean Scr of the rest patients
      preoperatively was 187.16 +/- 94.12 compared to 140.99 +/- 57.92 umol/L by the
      end of 1-month follow-up period (p = 0.019). The same findings were observed in
      GFR in that preoperatively it was 43.80 +/- 24.74 ml/min and by the end of the 1
      month follow-up it was 49.55 +/- 21.18 ml/min (p = 0.05).
      CONCLUSIONS/SIGNIFICANCE: Combined MPCNL and RIRS management effectively decrease
      the number and size of percutaneous access tracts, which is safe, feasible, and
      efficient for managing staghorn calculi in solitary kidney with satisfactory SFR
      and reducing blood loss, potential morbidity associated with multiple tracts. The
      approach did not adversely affect renal function at both short-term and long-term
      follow-up.

PMID- 23119017
TI  - Integrative binding sites within intracellular termini of TRPV1 receptor.
AB  - TRPV1 is a nonselective cation channel that integrates wide range of painful
      stimuli. It has been shown that its activity could be modulated by intracellular
      ligands PIP2 or calmodulin (CaM). The detailed localization and description of
      PIP2 interaction sites remain unclear. Here, we used synthesized peptides and
      purified fusion proteins of intracellular regions of TRPV1 expressed in E.coli in
      combination with fluorescence anisotropy and surface plasmon resonance
      measurements to characterize the PIP2 binding to TRPV1. We characterized one PIP2
      binding site in TRPV1 N-terminal region, residues F189-V221, and two independent
      PIP2 binding sites in C-terminus: residues K688-K718 and L777-S820. Moreover we
      show that two regions, namely F189-V221 and L777-S820, overlap with previously
      localized CaM binding sites. For all the interactions the equilibrium
      dissociation constants were estimated. As the structural data regarding C
      terminus of TRPV1 are lacking, restraint-based molecular modeling combined with
      ligand docking was performed providing us with structural insight to the
      TRPV1/PIP2 binding. Our experimental results are in excellent agreement with our
      in silico predictions.

PMID- 23119018
TI  - Characterization of the Holliday junction resolving enzyme encoded by the
      Bacillus subtilis bacteriophage SPP1.
AB  - Recombination-dependent DNA replication, which is a central component of viral
      replication restart, is poorly understood in Firmicutes bacteriophages. Phage
      SPP1 initiates unidirectional theta DNA replication from a discrete replication
      origin (oriL), and when replication progresses, the fork might stall by the
      binding of the origin binding protein G38P to the late replication origin (oriR).
      Replication restart is dependent on viral recombination proteins to synthesize a
      linear head-to-tail concatemer, which is the substrate for viral DNA packaging.
      To identify new functions involved in this process, uncharacterized genes from
      phage SPP1 were analyzed. Immediately after infection, SPP1 transcribes a number
      of genes involved in recombination and replication from P(E2) and P(E3)
      promoters. Resequencing the region corresponding to the last two hypothetical
      genes transcribed from the P(E2) operon (genes 44 and 45) showed that they are in
      fact a single gene, re-annotated here as gene 44, that encodes a single
      polypeptide, named gene 44 product (G44P, 27.5 kDa). G44P shares a low but
      significant degree of identity in its C-terminal region with virus-encoded RusA
      like resolvases. The data presented here demonstrate that G44P, which is a dimer
      in solution, binds with high affinity but without sequence specificity to several
      double-stranded DNA recombination intermediates. G44P preferentially cleaves
      Holliday junctions, but also, with lower efficiency, replicated D-loops. It also
      partially complemented the loss of RecU resolvase activity in B. subtilis cells.
      These in vitro and in vivo data suggest a role for G44P in replication restart
      during the transition to concatemeric viral replication.

PMID- 23119019
TI  - A rapid MALDI-TOF MS identification database at genospecies level for clinical
      and environmental Aeromonas strains.
AB  - The genus Aeromonas has undergone a number of taxonomic and nomenclature
      revisions over the past 20 years, and new (sub)species and biogroups are
      continuously described. Standard identification methods such as biochemical
      characterization have deficiencies and do not allow clarification of the
      taxonomic position. This report describes the development of a matrix-assisted
      laser desorption/ionisation-time of flight mass spectrometry (MALDI-TOF MS)
      identification database for a rapid identification of clinical and environmental
      Aeromonas isolates.

PMID- 23119020
TI  - PairMotif: A new pattern-driven algorithm for planted (l, d) DNA motif search.
AB  - Motif search is a fundamental problem in bioinformatics with an important
      application in locating transcription factor binding sites (TFBSs) in DNA
      sequences. The exact algorithms can report all (l, d) motifs and find the best
      one under a specific objective function. However, it is still a challenging task
      to identify weak motifs, since either a large amount of memory or execution time
      is required by current exact algorithms. A new exact algorithm, PairMotif, is
      proposed for planted (l, d) motif search (PMS) in this paper. To effectively
      reduce both candidate motifs and scanned l-mers, multiple pairs of l-mers with
      relatively large distances are selected from input sequences to restrict the
      search space. Comparisons with several recently proposed algorithms show that
      PairMotif requires less storage space and runs faster on most PMS instances.
      Particularly, among the algorithms compared, only PairMotif can solve the weak
      instance (27, 9) within 10 hours. Moreover, the performance of PairMotif is
      stable over the sequence length, which allows it to identify motifs in longer
      sequences. For the real biological data, experimental results demonstrate the
      validity of the proposed algorithm.

PMID- 23119021
TI  - Facilitation and competition among invasive plants: a field experiment with
      alligatorweed and water hyacinth.
AB  - Ecosystems that are heavily invaded by an exotic species often contain abundant
      populations of other invasive species. This may reflect shared responses to a
      common factor, but may also reflect positive interactions among these exotic
      species. Armand Bayou (Pasadena, TX) is one such ecosystem where multiple species
      of invasive aquatic plants are common. We used this system to investigate whether
      presence of one exotic species made subsequent invasions by other exotic species
      more likely, less likely, or if it had no effect. We performed an experiment in
      which we selectively removed exotic rooted and/or floating aquatic plant species
      and tracked subsequent colonization and growth of native and invasive species.
      This allowed us to quantify how presence or absence of one plant functional group
      influenced the likelihood of successful invasion by members of the other
      functional group. We found that presence of alligatorweed (rooted plant)
      decreased establishment of new water hyacinth (free-floating plant) patches but
      increased growth of hyacinth in established patches, with an overall net positive
      effect on success of water hyacinth. Water hyacinth presence had no effect on
      establishment of alligatorweed but decreased growth of existing alligatorweed
      patches, with an overall net negative effect on success of alligatorweed.
      Moreover, observational data showed positive correlations between hyacinth and
      alligatorweed with hyacinth, on average, more abundant. The negative effect of
      hyacinth on alligatorweed growth implies competition, not strong mutual
      facilitation (invasional meltdown), is occurring in this system. Removal of
      hyacinth may increase alligatorweed invasion through release from competition.
      However, removal of alligatorweed may have more complex effects on hyacinth patch
      dynamics because there were strong opposing effects on establishment versus
      growth. The mix of positive and negative interactions between floating and rooted
      aquatic plants may influence local population dynamics of each group and thus
      overall invasion pressure in this watershed.

PMID- 23119022
TI  - Regeneration of alveolar type I and II cells from Scgb1a1-expressing cells
      following severe pulmonary damage induced by bleomycin and influenza.
AB  - The lung comprises an extensive surface of epithelia constantly exposed to
      environmental insults. Maintaining the integrity of the alveolar epithelia is
      critical for lung function and gaseous exchange. However, following severe
      pulmonary damage, what progenitor cells give rise to alveolar type I and II cells
      during the regeneration of alveolar epithelia has not been fully determined. In
      this study, we have investigated this issue by using transgenic mice in which
      Scgb1a1-expressing cells and their progeny can be genetically labeled with EGFP.
      We show that following severe alveolar damage induced either by bleomycin or by
      infection with influenza virus, the majority of the newly generated alveolar type
      II cells in the damaged parenchyma were labeled with EGFP. A large proportion of
      EGFP-expressing type I cells were also observed among the type II cells. These
      findings strongly suggest that Scgb1a1-expressing cells, most likely Clara cells,
      are a major cell type that gives rise to alveolar type I and II cells during the
      regeneration of alveolar epithelia in response to severe pulmonary damage in
      mice.

PMID- 23119023
TI  - NT-ProBNP levels in saliva and its clinical relevance to heart failure.
AB  - BACKGROUND: Current blood based diagnostic assays to detect heart failure (HF)
      have large intra-individual and inter-individual variations which have made it
      difficult to determine whether the changes in the analyte levels reflect an
      actual change in disease activity. Human saliva mirrors the body's health and
      well being and ~20% of proteins that are present in blood are also found in
      saliva. Saliva has numerous advantages over blood as a diagnostic fluid which
      allows for a non-invasive, simple, and safe sample collection. The aim of our
      study was to develop an immunoassay to detect NT-proBNP in saliva and to
      determine if there is a correlation with blood levels. METHODS: Saliva samples
      were collected from healthy volunteers (n = 40) who had no underlying heart
      conditions and HF patients (n = 45) at rest. Samples were stored at -80 degrees C
      until analysis. A customised homogeneous sandwich AlphaLISA((R)) immunoassay was
      used to quantify NT-proBNP levels in saliva. RESULTS: Our NT-proBNP immunoassay
      was validated against a commercial Roche assay on plasma samples collected from
      HF patients (n = 37) and the correlation was r(2) = 0.78 (p<0.01, y = 1.705*
      +1910.8). The median salivary NT-proBNP levels in the healthy and HF participants
      were <16 pg/mL and 76.8 pg/mL, respectively. The salivary NT-proBNP immunoassay
      showed a clinical sensitivity of 82.2% and specificity of 100%, positive
      predictive value of 100% and negative predictive value of 83.3%, with an overall
      diagnostic accuracy of 90.6%. CONCLUSION: We have firstly demonstrated that NT
      proBNP can be detected in saliva and that the levels were higher in heart failure
      patients compared with healthy control subjects. Further studies will be needed
      to demonstrate the clinical relevance of salivary NT-proBNP in unselected,
      previously undiagnosed populations.

PMID- 23119024
TI  - Scaffold-based pan-agonist design for the PPARalpha, PPARbeta and PPARgamma
      receptors.
AB  - As important members of nuclear receptor superfamily, Peroxisome proliferator
      activated receptors (PPAR) play essential roles in regulating cellular
      differentiation, development, metabolism, and tumorigenesis of higher organisms.
      The PPAR receptors have 3 identified subtypes: PPARalpha, PPARbeta and PPARgamma,
      all of which have been treated as attractive targets for developing drugs to
      treat type 2 diabetes. Due to the undesirable side-effects, many PPAR agonists
      including PPARalpha/gamma and PPARbeta/gamma dual agonists are stopped by US FDA
      in the clinical trials. An alternative strategy is to design novel pan-agonist
      that can simultaneously activate PPARalpha, PPARbeta and PPARgamma. Under such an
      idea, in the current study we adopted the core hopping algorithm and glide
      docking procedure to generate 7 novel compounds based on a typical PPAR pan
      agonist LY465608. It was observed by the docking procedures and molecular
      dynamics simulations that the compounds generated by the core hopping and glide
      docking not only possessed the similar functions as the original LY465608
      compound to activate PPARalpha, PPARbeta and PPARgamma receptors, but also had
      more favorable conformation for binding to the PPAR receptors. The additional
      absorption, distribution, metabolism and excretion (ADME) predictions showed that
      the 7 compounds (especially Cpd#1) hold high potential to be novel lead compounds
      for the PPAR pan-agonist. Our findings can provide a new strategy or useful
      insights for designing the effective pan-agonists against the type 2 diabetes.

PMID- 23119025
TI  - Real-time sensing of cell morphology by infrared waveguide spectroscopy.
AB  - We demonstrate that a live epithelial cell monolayer can act as a planar
      waveguide. Our infrared reflectivity measurements show that highly differentiated
      simple epithelial cells, which maintain tight intercellular connectivity, support
      efficient waveguiding of the infrared light in the spectral region of 1.4-2.5 um
      and 3.5-4 um. The wavelength and the magnitude of the waveguide mode resonances
      disclose quantitative dynamic information on cell height and cell-cell
      connectivity. To demonstrate this we show two experiments. In the first one we
      trace in real-time the kinetics of the disruption of cell-cell contacts induced
      by calcium depletion. In the second one we show that cell treatment with the PI3
      kinase inhibitor LY294002 results in a progressive decrease in cell height
      without affecting intercellular connectivity. Our data suggest that infrared
      waveguide spectroscopy can be used as a novel bio-sensing approach for studying
      the morphology of epithelial cell sheets in real-time, label-free manner and with
      high spatial-temporal resolution.

PMID- 23119027
TI  - Ivermectin inhibits growth of Chlamydia trachomatis in epithelial cells.
AB  - Ivermectin is currently approved for treatment of both clinical and veterinary
      infections by nematodes, including Onchocerca cervicalis in horses and Onchocerca
      volvulus in humans. However, ivermectin has never been shown to be effective
      against bacterial pathogens. Here we show that ivermectin also inhibits infection
      of epithelial cells by the bacterial pathogen, Chlamydia trachomatis, at doses
      that could be envisioned clinically for sexually-transmitted or ocular infections
      by Chlamydia.

PMID- 23119026
TI  - Identification of new differentially methylated genes that have potential
      functional consequences in prostate cancer.
AB  - Many differentially methylated genes have been identified in prostate cancer
      (PCa), primarily using candidate gene-based assays. Recently, several global DNA
      methylation profiles have been reported in PCa, however, each of these has
      weaknesses in terms of ability to observe global DNA methylation alterations in
      PCa. We hypothesize that there remains unidentified aberrant DNA methylation in
      PCa, which may be identified using higher resolution assay methods. We used the
      newly developed Illumina HumanMethylation450 BeadChip in PCa (n = 19) and
      adjacent normal tissues (n = 4) and combined these with gene expression data for
      identifying new DNA methylation that may have functional consequences in PCa
      development and progression. We also confirmed our methylation results in an
      independent data set. Two aberrant DNA methylation genes were validated among an
      additional 56 PCa samples and 55 adjacent normal tissues. A total 28,735 CpG
      sites showed significant differences in DNA methylation (FDR adjusted P<0.05),
      defined as a mean methylation difference of at least 20% between PCa and normal
      samples. Furthermore, a total of 122 genes had more than one differentially
      methylated CpG site in their promoter region and a gene expression pattern that
      was inverse to the direction of change in DNA methylation (e.g. decreased
      expression with increased methylation, and vice-versa). Aberrant DNA methylation
      of two genes, AOX1 and SPON2, were confirmed via bisulfate sequencing, with most
      of the respective CpG sites showing significant differences between tumor samples
      and normal tissues. The AOX1 promoter region showed hypermethylation in 92.6% of
      54 tested PCa samples in contrast to only three out of 53 tested normal tissues.
      This study used a new BeadChip combined with gene expression data in PCa to
      identify novel differentially methylated CpG sites located within genes. The
      newly identified differentially methylated genes may be used as biomarkers for
      PCa diagnosis.

PMID- 23119028
TI  - Modeling intracerebral hemorrhage growth and response to anticoagulation.
AB  - The mechanism for hemorrhage enlargement in the brain, a key determinant of
      patient outcome following hemorrhagic stroke, is unknown. We performed computer
      based stochastic simulation of one proposed mechanism, in which hemorrhages grow
      in "domino" fashion via secondary shearing of neighboring vessel segments.
      Hemorrhages were simulated by creating an initial site of primary bleeding and an
      associated risk of secondary rupture at adjacent sites that decayed over time.
      Under particular combinations of parameters for likelihood of secondary rupture
      and time-dependent decay, a subset of lesions expanded, creating a bimodal
      distribution of microbleeds and macrobleeds. Systematic variation of the model to
      simulate anticoagulation yielded increases in both macrobleed occurrence (26.9%,
      53.2%, and 70.0% of all hemorrhagic events under conditions simulating no, low
      level, and high-level anticoagulation) and final hemorrhage size (median volumes
      111, 276, and 412 under the same three conditions), consistent with data from
      patients with anticoagulant-related brain hemorrhages. Reversal from simulated
      high-level anticoagulation to normal coagulation was able to reduce final
      hemorrhage size only if applied relatively early in the course of hemorrhage
      expansion. These findings suggest that a model based on a secondary shearing
      mechanism can account for some of the clinically observed properties of
      intracerebral hemorrhage, including the bimodal distribution of volumes and the
      enhanced hemorrhage growth seen with anticoagulation. Future iterations of this
      model may be useful for elucidating the effects of hemorrhage growth of factors
      related to secondary shearing (such as small vessel pathology) or time-dependent
      decay (such as hemostatic agents).

PMID- 23119029
TI  - Src-mediated cross-talk between farnesoid X and epidermal growth factor receptors
      inhibits human intestinal cell proliferation and tumorigenesis.
AB  - Besides its essential role in controlling bile acid and lipid metabolism, the
      farnesoid X receptor (FXR) protects against intestinal tumorigenesis by promoting
      apoptosis and inhibiting cell proliferation. However, the mechanisms underlying
      these anti-proliferative actions of FXR remain to be elucidated. In the present
      study, we examined the effects of FXR activation (FXR overexpression and
      treatment with an FXR agonist GW4064) and inactivation (treatment with FXR siRNA
      and an FXR antagonist guggulsterone) on colon cancer cell proliferation in vitro
      using human colon cancer cell lines (H508, SNU-C4 and HT-29) and in vivo using
      xenografts in nude mice. Blocking FXR activity with guggulsterone stimulated time
      and dose-dependent EGFR (Tyr845) phosphorylation and ERK activation. In
      contrast, FXR overexpression and activation with GW4064 attenuated cell
      proliferation by down-regulating EGFR (Tyr845) phosphorylation and ERK
      activation. Treatment with guggulsterone and GW4064 also caused dose-dependent
      changes in Src (Tyr416) phosphorylation. In stably-transfected human colon cancer
      cells, overexpression of FXR reduced EGFR, ERK, Src phosphorylation and cell
      proliferation, and in nude mice attenuated the growth of human colon cancer
      xenografts (64% reduction in tumor volume; 47% reduction in tumor weight; both
      P<0.01). Moreover, guggulsterone-induced EGFR and ERK phosphorylation and cell
      proliferation were abolished by inhibiting activation of Src, EGFR and MEK.
      Collectively these data support the novel conclusion that in human colon cancer
      cells Src-mediated cross-talk between FXR and EGFR modulates ERK phosphorylation,
      thereby regulating intestinal cell proliferation and tumorigenesis.

PMID- 23119030
TI  - Regional variation in aortic AT1b receptor mRNA abundance is associated with
      contractility but unrelated to atherosclerosis and aortic aneurysms.
AB  - BACKGROUND: Angiotensin II (AngII), the main bioactive peptide of the renin
      angiotensin system, exerts most of its biological actions through stimulation of
      AngII type 1 (AT1) receptors. This receptor is expressed as 2 structurally
      similar subtypes in rodents, termed AT1a and AT1b. Although AT1a receptors have
      been studied comprehensively, roles of AT1b receptors in the aorta have not been
      defined. METHODOLOGY/RESULTS: We initially compared the regional distribution of
      AT1b receptor mRNA with AT1a receptor mRNA in the aorta. mRNA abundance of both
      subtypes increased from the proximal to the distal aorta, with the greatest
      abundance in the infra-renal region. Corresponding to the high mRNA abundance for
      both receptors, only aortic rings from the infra-renal aorta contracted in
      response to AngII stimulation. Despite the presence of both receptor transcripts,
      deletion of AT1b receptors, but not AT1a receptors, diminished AngII-induced
      contractility. To determine whether absence of AT1b receptors influenced aortic
      pathologies, we bred AT1b receptor deficient mice into an LDL receptor deficient
      background. Mice were fed a diet enriched in saturated fat and infused with AngII
      (1,000 ng/kg/min). Parameters that could influence development of aortic
      pathologies, including systolic blood pressure and plasma cholesterol
      concentrations, were not impacted by AT1b receptor deficiency. Absence of AT1b
      receptors also had no effect on size of aortic atherosclerotic lesions and aortic
      aneurysms in both the ascending and abdominal regions. CONCLUSIONS/SIGNIFICANCE:
      Regional abundance of AT1b receptor mRNA coincided with AngII-induced regional
      contractility, but it was not associated with AngII-induced aortic pathologies.

PMID- 23119031
TI  - The expression of superoxide dismutase (SOD) and a putative ABC transporter
      permease is inversely correlated during biofilm formation in Listeria
      monocytogenes 4b G.
AB  - Little is known about the molecular basis of biofilm formation in Listeria
      monocytogenes. The superoxide dismutase (SOD) of the deletion mutant of lm.G_1771
      gene, which encodes for a putative ABC transporter permease, is highly expressed
      in biofilm. In this study, the sod gene deletion mutant Deltasod, and double
      deletion mutant of the sod and lm. G_1771 genes Delta1771Deltasod were used to
      investigate the role of SOD and its relationship to the expression of the
      putative ABC transporter permease in biofilm formation. Our results showed that
      the ability to form a biofilm was significantly reduced in the Deltasod mutant
      and the Delta1771Deltasod double mutant. Both Deltasod and Delta1771Deltasod
      mutants exhibited slow growth phenotypes and produced more reactive oxygen
      species (ROS). The growth was inhibited in the mutants by methyl viologen (MV,
      internal oxygen radical generator) treatment. In addition, the expression of one
      oxidation resistance gene (kat), two stress regulators encoding genes (perR and
      sigB), and one DNA repair gene (recA) were analyzed in both the wild-type L.
      monocytogenes 4b G and the deletion mutants by RT-qPCR. The expression levels of
      the four genes were increased in the deletion mutants when biofilms were formed.
      Taken together, our data indicated that SOD played an important role in biofilm
      formation through coping with the oxidant burden in deficient antioxidant
      defenses.

PMID- 23119032
TI  - A drought resistance-promoting microbiome is selected by root system under desert
      farming.
AB  - BACKGROUND: Traditional agro-systems in arid areas are a bulwark for preserving
      soil stability and fertility, in the sight of "reverse desertification".
      Nevertheless, the impact of desert farming practices on the diversity and
      abundance of the plant associated microbiome is poorly characterized, including
      its functional role in supporting plant development under drought stress.
      METHODOLOGY/PRINCIPAL FINDINGS: We assessed the structure of the microbiome
      associated to the drought-sensitive pepper plant (Capsicum annuum L.) cultivated
      in a traditional Egyptian farm, focusing on microbe contribution to a crucial
      ecosystem service, i.e. plant growth under water deficit. The root system was
      dissected by sampling root/soil with a different degree of association to the
      plant: the endosphere, the rhizosphere and the root surrounding soil that were
      compared to the uncultivated soil. Bacterial community structure and diversity,
      determined by using Denaturing Gradient Gel Electrophoresis, differed according
      to the microhabitat, indicating a selective pressure determined by the plant
      activity. Similarly, culturable bacteria genera showed different distribution in
      the three root system fractions. Bacillus spp. (68% of the isolates) were mainly
      recovered from the endosphere, while rhizosphere and the root surrounding soil
      fractions were dominated by Klebsiella spp. (61% and 44% respectively). Most of
      the isolates (95%) presented in vitro multiple plant growth promoting (PGP)
      activities and stress resistance capabilities, but their distribution was
      different among the root system fractions analyzed, with enhanced abilities for
      Bacillus and the rhizobacteria strains. We show that the C. annuum rhizosphere
      under desert farming enriched populations of PGP bacteria capable of enhancing
      plant photosynthetic activity and biomass synthesis (up to 40%) under drought
      stress. CONCLUSIONS/SIGNIFICANCE: Crop cultivation provides critical ecosystem
      services in arid lands with the plant root system acting as a "resource island"
      able to attract and select microbial communities endowed with multiple PGP traits
      that sustain plant development under water limiting conditions.

PMID- 23119033
TI  - Maternal vitamin C deficiency during pregnancy persistently impairs hippocampal
      neurogenesis in offspring of guinea pigs.
AB  - While having the highest vitamin C (VitC) concentrations in the body, specific
      functions of VitC in the brain have only recently been acknowledged. We have
      shown that postnatal VitC deficiency in guinea pigs causes impairment of
      hippocampal memory function and leads to 30% less neurons. This study
      investigates how prenatal VitC deficiency affects postnatal hippocampal
      development and if any such effect can be reversed by postnatal VitC repletion.
      Eighty pregnant Dunkin Hartley guinea pig dams were randomized into weight
      stratified groups receiving High (900 mg) or Low (100 mg) VitC per kg diet.
      Newborn pups (n = 157) were randomized into a total of four postnatal feeding
      regimens: High/High (Control); High/Low (Depleted), Low/Low (Deficient); and
      Low/High (Repleted). Proliferation and migration of newborn cells in the dentate
      gyrus was assessed by BrdU labeling and hippocampal volumes were determined by
      stereology. Prenatal VitC deficiency resulted in a significant reduction in
      postnatal hippocampal volume (P<0.001) which was not reversed by postnatal
      repletion. There was no difference in postnatal cellular proliferation and
      survival rates in the hippocampus between dietary groups, however, migration of
      newborn cells into the granular layer of the hippocampus dentate gyrus was
      significantly reduced in prenatally deficient animals (P<0.01). We conclude that
      a prenatal VitC deficiency in guinea pigs leads to persistent impairment of
      postnatal hippocampal development which is not alleviated by postnatal repletion.
      Our findings place attention on a yet unrecognized consequence of marginal VitC
      deficiency during pregnancy.

PMID- 23119034
TI  - Impact of age on the cancer-specific survival of patients with localized renal
      cell carcinoma: martingale residual and competing risks analysis.
AB  - BACKGROUND: Age at diagnosis has been shown to be an independent prognostic
      factor of localized renal cell carcinoma (RCC) in several studies. We used
      contemporary statistical methods to reevaluate the effect of age on the cancer
      specific survival (CSS) of localized RCC. METHODS AND FINDINGS: 1,147 patients
      with localized RCC who underwent radical nephrectomy between 1993 and 2009 were
      identified in our four institutions. The association between age and CSS was
      estimated, and the potential threshold was identified by a univariate Cox model
      and by martingale residual analysis. Competing risks regression was used to
      identify the independent impact of age on CSS. The median age was 52 years
      (range, 19-84 years). The median follow-up was 61 months (range, 6-144 months)
      for survivors. A steep increasing smoothed martingale residual plot indicated an
      adverse prognostic effect of age on CSS. The age cut-off of 45 years was most
      predictive of CSS on univariate Cox analysis and martingale residual analysis (p
      = 0.005). Age <=45 years was independently associated with a higher CSS rate in
      the multivariate Cox regression model (HR = 1.59, 95% CI = 1.05-2.40, p = 0.027)
      as well as in competing risks regression (HR = 3.60, 95% CI = 1.93-6.71, p =
      0.001). CONCLUSIONS: Increasing age was associated with a higher incidence of
      cancer-specific mortality of localized RCC. Age dichotomized at 45 years would
      maximize the predictive value of age on CSS, and independently predict the CSS of
      patients with localized RCC.

PMID- 23119035
TI  - Brain processing of biologically relevant odors in the awake rat, as revealed by
      manganese-enhanced MRI.
AB  - BACKGROUND: So far, an overall view of olfactory structures activated by natural
      biologically relevant odors in the awake rat is not available. Manganese-enhanced
      MRI (MEMRI) is appropriate for this purpose. While MEMRI has been used for
      anatomical labeling of olfactory pathways, functional imaging analyses have not
      yet been performed beyond the olfactory bulb. Here, we have used MEMRI for
      functional imaging of rat central olfactory structures and for comparing
      activation maps obtained with odors conveying different biological messages.
      METHODOLOGY/PRINCIPAL FINDINGS: Odors of male fox feces and of chocolate flavored
      cereals were used to stimulate conscious rats previously treated by intranasal
      instillation of manganese (Mn). MEMRI activation maps showed Mn enhancement all
      along the primary olfactory cortex. Mn enhancement elicited by male fox feces
      odor and to a lesser extent that elicited by chocolate odor, differed from that
      elicited by deodorized air. This result was partly confirmed by c-Fos
      immunohistochemistry in the piriform cortex. CONCLUSION/SIGNIFICANCE: By
      providing an overall image of brain structures activated in awake rats by odorous
      stimulation, and by showing that Mn enhancement is differently sensitive to
      different stimulating odors, the present results demonstrate the interest of
      MEMRI for functional studies of olfaction in the primary olfactory cortex of
      laboratory small animals, under conditions close to natural perception. Finally,
      the factors that may cause the variability of the MEMRI signal in response to
      different odor are discussed.

PMID- 23119036
TI  - In vivo micro-CT assessment of airway remodeling in a flexible OVA-sensitized
      murine model of asthma.
AB  - Airway remodeling is a major pathological feature of asthma. Up to now, its
      quantification still requires invasive methods. In this study, we aimed at
      determining whether in vivo micro-computed tomography (micro-CT) is able to
      demonstrate allergen-induced airway remodeling in a flexible mouse model of
      asthma. Sixty Balb/c mice were challenged intranasally with ovalbumin or saline
      at 3 different endpoints (Days 35, 75, and 110). All mice underwent
      plethysmography at baseline and just prior to respiratory-gated micro-CT. Mice
      were then sacrificed to assess bronchoalveolar lavage and lung histology. From
      micro-CT images (voxel size = 46*46*46 um), the numerical values of total lung
      attenuation, peribronchial attenuation (PBA), and PBA normalized by total lung
      attenuation were extracted. Each parameter was compared between OVA and control
      mice and correlation coefficients were calculated between micro-CT and
      histological data. As compared to control animals, ovalbumin-sensitized mice
      exhibited inflammation alone (Day 35), remodeling alone (Day 110) or both
      inflammation and remodeling (Day 75). Normalized PBA was significantly greater in
      mice exhibiting bronchial remodeling either alone or in combination with
      inflammation. Normalized PBA correlated with various remodeling markers such as
      bronchial smooth muscle size or peribronchial fibrosis. These findings suggest
      that micro-CT may help monitor remodeling non-invasively in asthmatic mice when
      testing new drugs targeting airway remodeling in pre-clinical studies.

PMID- 23119039
TI  - Inferring predator behavior from attack rates on prey-replicas that differ in
      conspicuousness.
AB  - Behavioral ecologists and evolutionary biologists have long studied how predators
      respond to prey items novel in color and pattern. Because a predatory response is
      influenced by both the predator's ability to detect the prey and a post-detection
      behavioral response, variation among prey types in conspicuousness may confound
      inference about post-prey-detection predator behavior. That is, a relatively high
      attack rate on a given prey type may result primarily from enhanced
      conspicuousness and not predators' direct preference for that prey. Few studies,
      however, account for such variation in conspicuousness. In a field experiment, we
      measured predation rates on clay replicas of two aposematic forms of the poison
      dart frog Dendrobates pumilio, one novel and one familiar, and two cryptic
      controls. To ask whether predators prefer or avoid a novel aposematic prey form
      independently of conspicuousness differences among replicas, we first modeled the
      visual system of a typical avian predator. Then, we used this model to estimate
      replica contrast against a leaf litter background to test whether variation in
      contrast alone could explain variation in predator attack rate. We found that
      absolute predation rates did not differ among color forms. Predation rates
      relative to conspicuousness did, however, deviate significantly from expectation,
      suggesting that predators do make post-detection decisions to avoid or attack a
      given prey type. The direction of this deviation from expectation, though,
      depended on assumptions we made about how avian predators discriminate objects
      from the visual background. Our results show that it is important to account for
      prey conspicuousness when investigating predator behavior and also that existing
      models of predator visual systems need to be refined.

PMID- 23119038
TI  - Feeling music: integration of auditory and tactile inputs in musical meter
      perception.
AB  - Musicians often say that they not only hear, but also "feel" music. To explore
      the contribution of tactile information in "feeling" musical rhythm, we
      investigated the degree that auditory and tactile inputs are integrated in humans
      performing a musical meter recognition task. Subjects discriminated between two
      types of sequences, 'duple' (march-like rhythms) and 'triple' (waltz-like
      rhythms) presented in three conditions: 1) Unimodal inputs (auditory or tactile
      alone), 2) Various combinations of bimodal inputs, where sequences were
      distributed between the auditory and tactile channels such that a single channel
      did not produce coherent meter percepts, and 3) Simultaneously presented bimodal
      inputs where the two channels contained congruent or incongruent meter cues. We
      first show that meter is perceived similarly well (70%-85%) when tactile or
      auditory cues are presented alone. We next show in the bimodal experiments that
      auditory and tactile cues are integrated to produce coherent meter percepts.
      Performance is high (70%-90%) when all of the metrically important notes are
      assigned to one channel and is reduced to 60% when half of these notes are
      assigned to one channel. When the important notes are presented simultaneously to
      both channels, congruent cues enhance meter recognition (90%). Performance drops
      dramatically when subjects were presented with incongruent auditory cues (10%),
      as opposed to incongruent tactile cues (60%), demonstrating that auditory input
      dominates meter perception. We believe that these results are the first
      demonstration of cross-modal sensory grouping between any two senses.

PMID- 23119037
TI  - Quantitative proteomic analysis of the Hfq-regulon in Sinorhizobium meliloti
      2011.
AB  - Riboregulation stands for RNA-based control of gene expression. In bacteria,
      small non-coding RNAs (sRNAs) are a major class of riboregulatory elements, most
      of which act at the post-transcriptional level by base-pairing target mRNA genes.
      The RNA chaperone Hfq facilitates antisense interactions between target mRNAs and
      regulatory sRNAs, thus influencing mRNA stability and/or translation rate. In the
      alpha-proteobacterium Sinorhizobium meliloti strain 2011, the identification and
      detection of multiple sRNAs genes and the broadly pleitropic phenotype associated
      to the absence of a functional Hfq protein both support the existence of
      riboregulatory circuits controlling gene expression to ensure the fitness of this
      bacterium in both free living and symbiotic conditions. In order to identify
      target mRNAs subject to Hfq-dependent riboregulation, we have compared the
      proteome of an hfq mutant and the wild type S. meliloti by quantitative
      proteomics following protein labelling with (15)N. Among 2139 univocally
      identified proteins, a total of 195 proteins showed a differential abundance
      between the Hfq mutant and the wild type strain; 65 proteins accumulated >=2-fold
      whereas 130 were downregulated (<=0.5-fold) in the absence of Hfq. This profound
      proteomic impact implies a major role for Hfq on regulation of diverse
      physiological processes in S. meliloti, from transport of small molecules to
      homeostasis of iron and nitrogen. Changes in the cellular levels of proteins
      involved in transport of nucleotides, peptides and amino acids, and in iron
      homeostasis, were confirmed with phenotypic assays. These results represent the
      first quantitative proteomic analysis in S. meliloti. The comparative analysis of
      the hfq mutant proteome allowed identification of novel strongly Hfq-regulated
      genes in S. meliloti.

PMID- 23119041
TI  - Heterogeneity of inter-rater reliabilities of grant peer reviews and its
      determinants: a general estimating equations approach.
AB  - BACKGROUND: One of the most important weaknesses of the peer review process is
      that different reviewers' ratings of the same grant proposal typically differ.
      Studies on the inter-rater reliability of peer reviews mostly report only average
      values across all submitted proposals. But inter-rater reliabilities can vary
      depending on the scientific discipline or the requested grant sum, for instance.
      GOAL: Taking the Austrian Science Fund (FWF) as an example, we aimed to
      investigate empirically the heterogeneity of inter-rater reliabilities
      (intraclass correlation) and its determinants. METHODS: The data consisted of N =
      8,329 proposals with N = 23,414 overall ratings by reviewers, which were
      statistically analyzed using the generalized estimating equations approach (GEE).
      RESULTS: We found an overall intraclass correlation (ICC) of reviewer? ratings of
      rho = .259 with a 95% confidence interval of [.249,.279]. In humanities the ICCs
      were statistically significantly higher than in all other research areas except
      technical sciences. The ICC in biosciences deviated statistically significantly
      from the average ICC. Other factors (besides the research areas), such as the
      grant sum requested, had negligible influence on the ICC. CONCLUSIONS: Especially
      in biosciences, the number of reviewers of each proposal should be increased so
      as to increase the ICC.

PMID- 23119040
TI  - Differential Go/NoGo activity in both contingent negative variation and spectral
      power.
AB  - We investigated whether both the contingent negative variation (CNV), an event
      related potential index of preparatory brain activity, and event-related
      oscillatory EEG activity differentiated Go and NoGo trials in a delayed response
      task. CNV and spectral power (4-100 Hz) were calculated from EEG activity in the
      preparatory interval in 16 healthy adult participants. As previously reported,
      CNV amplitudes were higher in Go compared to NoGo trials. In addition, event
      related spectral power of the Go condition was reduced in the theta to low gamma
      range compared to the NoGo condition, confirming that preparing to respond is
      associated with modulation of event-related spectral activity as well as the CNV.
      Altogether, the impact of the experimental manipulation on both slow event
      related potentials and oscillatory EEG activity may reflect coordinated dynamic
      changes in the excitability of distributed neural networks involved in
      preparation.

PMID- 23119042
TI  - Mutation frequency and spectrum of mutations vary at different chromosomal
      positions of Pseudomonas putida.
AB  - It is still an open question whether mutation rate can vary across the bacterial
      chromosome. In this study, the occurrence of mutations within the same mutational
      target sequences at different chromosomal locations of Pseudomonas putida was
      monitored. For that purpose we constructed two mutation detection systems, one
      for monitoring the occurrence of a broad spectrum of mutations and transposition
      of IS element IS1411 inactivating LacI repressor, and another for detecting 1-bp
      deletions. Our results revealed that both the mutation frequency and the spectrum
      of mutations vary at different chromosomal positions. We observed higher mutation
      frequencies when the direction of transcription of the mutational target gene was
      opposite to the direction of replisome movement in the chromosome and vice versa,
      lower mutation frequency was accompanied with co-directional transcription and
      replication. Additionally, asymmetry of frameshift mutagenesis at homopolymeric
      and repetitive sequences during the leading and lagging-strand replication was
      found. The transposition frequency of IS1411 was also affected by the chromosomal
      location of the target site, which implies that regional differences in
      chromosomal topology may influence transposition of this mobile element. The
      occurrence of mutations in the P. putida chromosome was investigated both in
      growing and in stationary-phase bacteria. We found that the appearance of certain
      mutational hot spots is strongly affected by the chromosomal location of the
      mutational target sequence especially in growing bacteria. Also, artificial
      increasing transcription of the mutational target gene elevated the frequency of
      mutations in growing bacteria.

PMID- 23119044
TI  - Clinical presentations, antiplatelet strategies and prognosis of patients with
      stent thrombosis: an observational study of 140 patients.
AB  - BACKGROUND: Until now there has been scarce evidence regarding an optimal
      antiplatelet strategy and clinical outcomes for patients who had suffered from
      stent thrombosis (ST). METHODS AND RESULTS: 140 patients who suffered from stent
      thrombosis were prospectively registered. Patients received dual (aspirin and 150
      mg clopidogrel, N = 66) or triple (additional cilostazol, N = 74) antiplatelet
      therapy at the physician's discretion. Thereafter platelet reactivity and one
      year clinical outcomes were analyzed. The primary outcome included the composite
      of cardiac death, non-fatal myocardial infarction (MI) or stroke at one
      year,which developed in 41 (29.3%) patients, consisting of 31 (22.1%) cardiac
      death, 9 (6.4%) non-fatal MI and 1 (1.4%) stroke. Recurrent definite and probable
      ST according to ARC definition was observed in 8 (5.7%) and 14 (10.0%) patients,
      respectively. Triple therapy was associated with significantly lower platelet
      reactivities (50.2 +/- 17.8, % vs. 59.6 +/- 17.2, %, P = 0.002) compared to high
      dose dual antiplatelet therapy. However, the incidence of primary events (24.3%
      vs. 34.8%, P = 0.172) did not differ between triple and dual antiplatelet
      therapies. High on-treatment platelet reactivity (HR: 8.35, 95% CI: 2.234~30.867,
      P = 0.002) and diabetes (HR: 3.732, 95% CI: 1.353~10.298, P = 0.011) were
      independent predictors of primary events. CONCLUSIONS: Patients who suffered from
      stent thrombosis have a poor prognosis even after revascularization with
      intensive antiplatelet therapy. Triple antiplatelet therapy was more effective in
      reducing on-treatment platelet reactivity, compared to high dose dual
      antiplatelet therapy.

PMID- 23119043
TI  - Intravenous delivery of targeted liposomes to amyloid-beta pathology in APP/PSEN1
      transgenic mice.
AB  - Extracellular amyloid-beta (Abeta) plaques and intracellular neurofibrillary
      tangles constitute the major neuropathological hallmarks of Alzheimer's disease
      (AD). It is now apparent that parenchymal Abeta plaque deposition precedes
      behavioral signs of disease by several years. The development of agents that can
      target these plaques may be useful as diagnostic or therapeutic tools. In this
      study, we synthesized an Abeta-targeted lipid conjugate, incorporated it in
      stealth liposomal nanoparticles and tested their ability to bind amyloid plaque
      deposits in an AD mouse model. The results show that the particles maintain
      binding profiles to synthetic Abeta aggregates comparable to the free ligand, and
      selectively bind Abeta plaque deposits in brain tissue sections of an AD mouse
      model (APP/PSEN1 transgenic mice) with high efficiency. When administered
      intravenously, these long circulating nanoparticles appear to cross the blood
      brain barrier and bind to Abeta plaque deposits, labeling parenchymal amyloid
      deposits and vascular amyloid characteristic of cerebral amyloid angiopathy.

PMID- 23119045
TI  - Diversity and composition of demersal fishes along a depth gradient assessed by
      baited remote underwater stereo-video.
AB  - BACKGROUND: Continental slopes are among the steepest environmental gradients on
      earth. However, they still lack finer quantification and characterisation of
      their faunal diversity patterns for many parts of the world.
      METHODOLOGY/PRINCIPAL FINDINGS: Changes in fish community structure and diversity
      along a depth gradient from 50 to 1200 m were studied from replicated stereo
      baited remote underwater video deployments within each of seven depth zones at
      three locations in north-eastern New Zealand. Strong, but gradual turnover in the
      identities of species and community structure was observed with increasing depth.
      Species richness peaked in shallow depths, followed by a decrease beyond 100 m to
      a stable average value from 700 to 1200 m. Evenness increased to 700 m depth,
      followed by a decrease to 1200 m. Average taxonomic distinctness ?(+) response
      was unimodal with a peak at 300 m. The variation in taxonomic distinctness
      Lambda(+) first decreased sharply from 50 to 300 m, then increased beyond 500 m
      depth, indicating that species from deep samples belonged to more distant
      taxonomic groups than those from shallow samples. Fishes with northern
      distributions progressively decreased in their proportional representation with
      depth whereas those with widespread distributions increased.
      CONCLUSIONS/SIGNIFICANCE: This study provides the first characterization of
      diversity patterns for bait-attracted fish species on continental slopes in New
      Zealand and is an imperative primary step towards development of explanatory and
      predictive ecological models, as well as being fundamental for the implementation
      of efficient management and conservation strategies for fishery resources.

PMID- 23119047
TI  - Waist circumference and abdominal obesity among older adults: patterns,
      prevalence and trends.
AB  - OBJECTIVES: To describe the patterns and trends in waist circumference and
      abdominal obesity for those aged 70-89 contrasting the standard and new age
      related cut-points, and to investigate how they vary with time, age and
      educational level. METHODS: The subjects were 7129 men and 9244 women aged 70-89
      years who participated in the Health Survey for England during 1993-2010. The
      outcome measures were the percentiles of waist circumference and standard and new
      indicators of abdominal obesity based on waist circumference. Binomial and
      quantile regression were used to investigate the relationship with key
      explanatory variables. RESULTS: The distribution of waist circumference among
      community-dwelling older adults in England has shifted upwards since 1993 (an
      increase in median of 4.5 cm in men and 5.1 cm in women). The prevalence of
      abdominal obesity has increased, while those in the low-risk group have
      decreased. Abdominal obesity was higher in those aged 70-79 compared to 80-89,
      and in those who left education earlier. The prevalence of abdominal obesity
      varies considerably with new and standard cut-points, which makes it impractical
      to use the new ones on a population that includes subjects across the adult age
      range. CONCLUSIONS: Obesity is increasing among the elderly, but more work is
      needed on devising age-appropriate indicators of high risk based on waist
      circumference.

PMID- 23119046
TI  - Deletion of the viral anti-apoptotic gene F1L in the HIV/AIDS vaccine candidate
      MVA-C enhances immune responses against HIV-1 antigens.
AB  - Vaccinia virus (VACV) encodes an anti-apoptotic Bcl-2-like protein F1 that acts
      as an inhibitor of caspase-9 and of the Bak/Bax checkpoint but the role of this
      gene in immune responses is not known. Because dendritic cells that have
      phagocytosed apoptotic infected cells cross-present viral antigens to cytotoxic T
      cells inducing an antigen-specific immunity, we hypothesized that deletion of the
      viral anti-apoptotic F1L gene might have a profound effect on the capacity of
      poxvirus vectors to activate specific immune responses to virus-expressed
      recombinant antigens. This has been tested in a mouse model with an F1L deletion
      mutant of the HIV/AIDS vaccine candidate MVA-C that expresses Env and Gag-Pol-Nef
      antigens (MVA-C-DeltaF1L). The viral gene F1L is not required for virus
      replication in cultured cells and its deletion in MVA-C induces extensive
      apoptosis and expression of immunomodulatory genes in infected cells. Analysis of
      the immune responses induced in BALB/c mice after DNA prime/MVA boost revealed
      that, in comparison with parental MVA-C, the mutant MVA-C-DeltaF1L improves the
      magnitude of the HIV-1-specific CD8 T cell adaptive immune responses and impacts
      on the CD8 T cell memory phase by enhancing the magnitude of the response,
      reducing the contraction phase and changing the memory differentiation pattern.
      These findings reveal the immunomodulatory role of F1L and that the loss of this
      gene is a valid strategy for the optimization of MVA as vaccine vector.

PMID- 23119048
TI  - Combination erlotinib-cisplatin and Atg3-mediated autophagy in erlotinib
      resistant lung cancer.
AB  - Tyrosine kinase inhibitors such as erlotinib are commonly used as a therapeutic
      agent against cancer due to its relatively low side-effect profile and, at times,
      greater efficacy. However, erlotinib resistance (ER) in non-small cell lung
      cancer is being recognized as a major problem. Therefore, understanding the
      mechanism behind ER and developing effective regimens are needed. Autophagy's
      role in cancer has been controversial and remains unclear. In this study, we
      examined the effectiveness of low dose erlotinib-cisplatin combination in
      erlotinib resistant lung adenocarcinoma (ERPC9) cells and the role of autophagy
      in ER. ERPC9 cells were established from erlotinib sensitive PC9 cells.
      Appropriate treatments were done over two days and cell survival was quantified
      with Alamar Blue assay. LC3II and regulatory proteins of autophagy were measured
      by western blot. Small interfering RNA (siRNA) was utilized to inhibit
      translation of the protein of interest. In ERPC9 cells, combination treatment
      induced synergistic cell death and a significant decrease in autophagy. At
      baseline, ERPC9 cells had a significantly higher LC3II and lower p-mTOR levels
      compared to PC9 cells. The addition of rapamycin increased resistance and 3
      methyladenine sensitized ERPC9 cells, indicating autophagy may be acting as a
      protective mechanism. Further examination revealed that ERPC9 cells harbored high
      baseline Atg3 levels. The high basal Atg3 was targeted and significantly lowered
      with combination treatment. siRNA transfection of Atg3 resulted in the reversal
      of ER; 42.0% more cells died in erlotinib-alone treatment with transfection
      compared to non-transfected ERPC9 cells. We reveal a novel role for Atg3 in the
      promotion of ER as the inhibition of Atg3 translation was able to result in the
      re-sensitization of ERPC9 cells to erlotinib-alone treatment. Also, we
      demonstrate that combination erlotinib-cisplatin is an effective treatment
      against erlotinib resistant cancer by targeting (down-regulating) Atg3 mediated
      autophagy and induction of apoptotic cell death.

PMID- 23119049
TI  - Modeling the contributions of Ca2+ flows to spontaneous Ca2+ oscillations and
      cortical spreading depression-triggered Ca2+ waves in astrocyte networks.
AB  - Astrocytes participate in brain functions through Ca(2+) signals, including
      Ca(2+) waves and Ca(2+) oscillations. Currently the mechanisms of Ca(2+) signals
      in astrocytes are not fully clear. Here, we present a computational model to
      specify the relative contributions of different Ca(2+) flows between the
      extracellular space, the cytoplasm and the endoplasmic reticulum of astrocytes to
      the generation of spontaneous Ca(2+) oscillations (CASs) and cortical spreading
      depression (CSD)-triggered Ca(2+) waves (CSDCWs) in a one-dimensional astrocyte
      network. This model shows that CASs depend primarily on Ca(2+) released from
      internal stores of astrocytes, and CSDCWs depend mainly on voltage-gated Ca(2+)
      influx. It predicts that voltage-gated Ca(2+) influx is able to generate Ca(2+)
      waves during the process of CSD even after depleting internal Ca(2+) stores.
      Furthermore, the model investigates the interactions between CASs and CSDCWs and
      shows that the pass of CSDCWs suppresses CASs, whereas CASs do not prevent the
      generation of CSDCWs. This work quantitatively analyzes the generation of
      astrocytic Ca(2+) signals and indicates different mechanisms underlying CSDCWs
      and non-CSDCWs. Research on the different types of Ca(2+) signals might help to
      understand the ways by which astrocytes participate in information processing in
      brain functions.

PMID- 23119050
TI  - Induction of CD36 and thrombospondin-1 in macrophages by hypoxia-inducible factor
      1 and its relevance in the inflammatory process.
AB  - Inflammation is part of a complex biological response of vascular tissue to
      pathogens or damaged cells. First inflammatory cells attempt to remove the
      injurious stimuli and this is followed by a healing process mediated principally
      by phagocytosis of senescent cells. Hypoxia and p38-MAPK are associated with
      inflammation, and hypoxia inducible factor 1 (HIF-1) has been detected in
      inflamed tissues. We aimed to analyse the role of p38-MAPK and HIF-1 in the
      transcriptional regulation of CD36, a class B scavenger receptor, and its ligand
      thrombospondin (TSP-1) in macrophages and to evaluate the involvement of this
      pathway in phagocytosis of apoptotic neutrophils. We have also assessed HIF
      1alpha, p38-MAPK and CD36 immunostaining in the mucosa of patients with
      inflammatory bowel disease. Results show that hypoxia increases neutrophil
      phagocytosis by macrophages and induces the expression of CD36 and TSP-1.
      Addition of a p38-MAPK inhibitor significantly reduced the increase in CD36 and
      TSP-1 expression provoked by hypoxia and decreased HIF-1alpha stabilization in
      macrophages. Transient transfection of macrophages with a miHIF-1alpha-targeting
      vector blocked the increase in mRNA expression of CD36 and TSP-1 during hypoxia
      and reduced phagocytosis, thus highlighting a role for the transcriptional
      activity of HIF-1. CD36 and TSP-1 were necessary for the phagocytosis of
      neutrophils induced by hypoxic macrophages, since functional blockade of these
      proteins undermined this process. Immunohistochemical studies revealed CD36, HIF
      1alpha and p38-MAPK expression in the mucosa of patients with inflammatory bowel
      disease. A positive and significant correlation between HIF-1alpha and CD36
      expression and CD36 and p38-MAPK expression was observed in cells of the lamina
      propria of the damaged mucosa. Our results demonstrate a HIF-1-dependent up
      regulation of CD36 and TSP-1 that mediates the increased phagocytosis of
      neutrophils by macrophages during hypoxia. Moreover, they suggest that CD36
      expression in the damaged mucosa of patients with inflammatory bowel disease
      depends on p38-MAPK and HIF-1 activity.

PMID- 23119052
TI  - Maternal effects may act as an adaptation mechanism for copepods facing pH and
      temperature changes.
AB  - Acidification of the seas, caused by increased dissolution of CO(2) into surface
      water, and global warming challenge the adaptation mechanisms of marine
      organisms. In boreal coastal environments, temperature and pH vary greatly
      seasonally, but sometimes also rapidly within hours due to upwelling events. We
      studied if copepod zooplankton living in a fluctuating environment are tolerant
      to climate change effects predicted for 2100, i.e., a temperature increase of 3
      degrees C and a pH decrease of 0.4. Egg production of the copepod Acartia sp. was
      followed over five consecutive days at four temperature and pH conditions (17
      degrees C/ambient pH; 17 degrees C/low pH; 20 degrees C/ambient pH; 20 degrees
      C/low pH). Egg production was higher in treatments with warmer temperature but
      the increase was smaller when copepods were simultaneously exposed to warmer
      temperature and lowered pH. To reveal if maternal effects are important in terms
      of adaptation to a changing environment, we conducted an egg transplantation
      experiment, where the produced eggs were moved to a different environment and egg
      hatching was monitored for three days. When pH changed between the egg production
      and hatching conditions, it resulted in lower hatching success, but the effect
      was diminished over the course of the experiment possibly due to improved
      maternal provisioning. Warmer egg production temperature induced a positive
      maternal effect and increased the egg hatching rate. Warmer hatching temperature
      resulted also in earlier hatching. However, the temperature effects appear to be
      dependent on the ambient sea temperature. Our preliminary results indicate that
      maternal effects are an important mechanism in the face of environmental change.

PMID- 23119051
TI  - A phage display selected 7-mer peptide inhibitor of the Tannerella forsythia
      metalloprotease-like enzyme Karilysin can be truncated to Ser-Trp-Phe-Pro.
AB  - Tannerella forsythia is a gram-negative bacteria, which is strongly associated
      with the development of periodontal disease. Karilysin is a newly identified
      metalloprotease-like enzyme, that is secreted from T. forsythia. Karilysin
      modulates the host immune response and is therefore considered a likely drug
      target. In this study peptides were selected towards the catalytic domain from
      Karilysin (Kly18) by phage display. The peptides were linear with low micromolar
      binding affinities. The two best binders (peptide14 and peptide15), shared the
      consensus sequence XWFPXXXGGG. A peptide15 fusion with Maltose Binding protein
      (MBP) was produced with peptide15 fused to the N-terminus of MBP. The peptide15
      MBP was expressed in E. coli and the purified fusion-protein was used to verify
      Kly18 specific binding. Chemically synthesised peptide15 (SWFPLRSGGG) could
      inhibit the enzymatic activity of both Kly18 and intact Karilysin (Kly48).
      Furthermore, peptide15 could slow down the autoprocessing of intact Kly48 to
      Kly18. The WFP motif was important for inhibition and a truncation study further
      demonstrated that the N-terminal serine was also essential for Kly18 inhibition.
      The SWFP peptide had a Ki value in the low micromolar range, which was similar to
      the intact peptide15. In conclusion SWFP is the first reported inhibitor of
      Karilysin and can be used as a valuable tool in structure-function studies of
      Karilysin.

PMID- 23119053
TI  - Non-silent story on synonymous sites in voltage-gated ion channel genes.
AB  - Synonymous mutations are usually referred to as "silent", but increasing evidence
      shows that they are not neutral in a wide range of organisms. We looked into the
      relationship between synonymous codon usage bias and residue importance of
      voltage-gated ion channel proteins in mice, rats, and humans. We tested whether
      translationally optimal codons are associated with transmembrane or channel
      forming regions, i.e., the sites that are particularly likely to be involved in
      the closing and opening of an ion channel. Our hypothesis is that translationally
      optimal codons are preferred at the sites within transmembrane domains or channel
      forming regions in voltage-gated ion channel genes to avoid mistranslation
      induced protein misfolding or loss-of-function. Using the Mantel-Haenszel
      procedure, which applies to categorical data, we found that translationally
      optimal codons are more likely to be used at transmembrane residues and the
      residues involved in channel-forming. We also found that the conservation level
      at synonymous sites in the transmembrane region is significantly higher than that
      in the non-transmembrane region. This study provides evidence that synonymous
      sites in voltage-gated ion channel genes are not neutral. Silent mutations at
      channel-related sites may lead to dysfunction of the ion channel.

PMID- 23119054
TI  - Zinc chelation reduces hippocampal neurogenesis after pilocarpine-induced
      seizure.
AB  - Several studies have shown that epileptic seizures increase hippocampal
      neurogenesis in the adult. However, the mechanism underlying increased
      neurogenesis after seizures remains largely unknown. Neurogenesis occurs in the
      subgranular zone (SGZ) of the hippocampus in the adult brain, although an
      understanding of why it actively occurs in this region has remained elusive. A
      high level of vesicular zinc is localized in the presynaptic terminals of the
      SGZ. Previously, we demonstrated that a possible correlation may exist between
      synaptic zinc localization and high rates of neurogenesis in this area after
      hypoglycemia. Using a lithium-pilocarpine model, we tested our hypothesis that
      zinc plays a key role in modulating hippocampal neurogenesis after seizure. Then,
      we injected the zinc chelator, clioquinol (CQ, 30 mg/kg), into the
      intraperitoneal space to reduce brain zinc availability. Neuronal death was
      detected with Fluoro Jade-B and NeuN staining to determine whether CQ has
      neuroprotective effects after seizure. The total number of degenerating and live
      neurons was similar in vehicle and in CQ treated rats at 1 week after seizure.
      Neurogenesis was evaluated using BrdU, Ki67 and doublecortin (DCX) immunostaining
      1 week after seizure. The number of BrdU, Ki67 and DCX positive cell was
      increased after seizure. However, the number of BrdU, Ki67 and DCX positive cells
      was significantly decreased by CQ treatment. Intracellular zinc chelator,
      N,N,N0,N-Tetrakis (2-pyridylmethyl) ethylenediamine (TPEN), also reduced seizure
      induced neurogenesis in the hippocampus. The present study shows that zinc
      chelation does not prevent neurodegeneration but does reduce seizure-induced
      progenitor cell proliferation and neurogenesis. Therefore, this study suggests
      that zinc has an essential role for modulating hippocampal neurogenesis after
      seizure.

PMID- 23119055
TI  - Identification of tympanic border cells as slow-cycling cells in the cochlea.
AB  - Mammalian cochlear sensory epithelial cells are believed to possess minimal
      regenerative potential because they halt proliferation during late stage of
      embryogenesis and never regenerate after birth. This means that sensorineural
      hearing loss caused by the death of cochlear sensory epithelial cells is a
      permanent condition. However, stem cells were recently identified in neonatal
      mice following dissociation of their inner ear organs. This suggests that
      regenerative therapy for sensorineural hearing loss may be possible.
      Unfortunately, dissociation distorts the microanatomy of the inner ear, making it
      difficult to determine the precise location of stem cells in unaltered specimens.
      To develop new therapeutic approaches based on sensory epithelial cell
      regeneration, the location of these stem cells must be elucidated. Stem cells
      normally proliferate at a slow rate in adult organs. In fact, so-called label
      retaining cells, or slow-cycling cells, of the brain and skin are recognized as
      stem cells. In this study, using the exogenous proliferation marker, 5'-bromo-2'
      deoxyuridine (BrdU) in combination with the endogenous proliferation marker Ki
      67, we identified tympanic border cells. These cells, which are located beneath
      the basilar membrane in vivo, represent slow-cycling cells of the murine cochlea.
      Immunohistochemically, these cells stained positive for the immature cell marker
      Nestin. But it will be difficult to achieve regeneration of the cochlear function
      because these slow-cycling cells disappear in the mature murine cochlea.

PMID- 23119058
TI  - Ecological succession, hydrology and carbon acquisition of biological soil crusts
      measured at the micro-scale.
AB  - The hydrological characteristics of biological soil crusts (BSCs) are not well
      understood. In particular the relationship between runoff and BSC surfaces at
      relatively large (>1 m(2)) scales is ambiguous. Further, there is a dearth of
      information on small scale (mm to cm) hydrological characterization of crust
      types which severely limits any interpretation of trends at larger scales. Site
      differences and broad classifications of BSCs as one soil surface type rather
      than into functional form exacerbate the problem. This study examines, for the
      first time, some hydrological characteristics and related surface variables of a
      range of crust types at one site and at a small scale (sub mm to mm). X-ray
      tomography and fine scale hydrological measurements were made on intact BSCs,
      followed by C and C isotopic analyses. A 'hump' shaped relationship was found
      between the successional stage/sensitivity to physical disturbance classification
      of BSCs and their hydrophobicity, and a similar but 'inverse hump' relationship
      exists with hydraulic conductivity. Several bivariate relationships were found
      between hydrological variables. Hydraulic conductivity and hydrophobicity of BSCs
      were closely related but this association was confounded by crust type. The
      surface coverage of crust and the microporosity 0.5 mm below the crust surface
      were closely associated irrespective of crust type. The delta (13)C signatures of
      the BSCs were also related to hydraulic conductivity, suggesting that the
      hydrological characteristics of BSCs alter the chemical processes of their
      immediate surroundings via the physiological response (C acquisition) of the
      crust itself. These small scale results illustrate the wide range of hydrological
      properties associated with BSCs, and suggest associations between the ecological
      successional stage/functional form of BSCs and their ecohydrological role that
      needs further examination.

PMID- 23119056
TI  - Developmental expression of Kv potassium channels at the axon initial segment of
      cultured hippocampal neurons.
AB  - Axonal outgrowth and the formation of the axon initial segment (AIS) are early
      events in the acquisition of neuronal polarity. The AIS is characterized by a
      high concentration of voltage-dependent sodium and potassium channels. However,
      the specific ion channel subunits present and their precise localization in this
      axonal subdomain vary both during development and among the types of neurons,
      probably determining their firing characteristics in response to stimulation.
      Here, we characterize the developmental expression of different subfamilies of
      voltage-gated potassium channels in the AISs of cultured mouse hippocampal
      neurons, including subunits Kv1.2, Kv2.2 and Kv7.2. In contrast to the early
      appearance of voltage-gated sodium channels and the Kv7.2 subunit at the AIS,
      Kv1.2 and Kv2.2 subunits were tethered at the AIS only after 10 days in vitro.
      Interestingly, we observed different patterns of Kv1.2 and Kv2.2 subunit
      expression, with each confined to distinct neuronal populations. The accumulation
      of Kv1.2 and Kv2.2 subunits at the AIS was dependent on ankyrin G tethering, it
      was not affected by disruption of the actin cytoskeleton and it was resistant to
      detergent extraction, as described previously for other AIS proteins. This
      distribution of potassium channels in the AIS further emphasizes the
      heterogeneity of this structure in different neuronal populations, as proposed
      previously, and suggests corresponding differences in action potential
      regulation.

PMID- 23119057
TI  - Prostatic acid phosphatase is required for the antinociceptive effects of
      thiamine and benfotiamine.
AB  - Thiamine (Vitamin B1) is an essential vitamin that must be obtained from the diet
      for proper neurological function. At higher doses, thiamine and benfotiamine (S
      benzoylthiamine O-monophosphate, BT)-a phosphorylated derivative of thiamine-have
      antinociceptive effects in animals and humans, although how these compounds
      inhibit pain is unknown. Here, we found that Prostatic acid phosphatase (PAP,
      ACPP) can dephosphorylate BT in vitro, in dorsal root ganglia (DRG) neurons and
      in primary-afferent axon terminals in the dorsal spinal cord. The
      dephosphorylated product S-benzoylthiamine (S-BT) then decomposes to O
      benzoylthiamine (O-BT) and to thiamine in a pH-dependent manner, independent of
      additional enzymes. This unique reaction mechanism reveals that BT only requires
      a phosphatase for conversion to thiamine. However, we found that the
      antinociceptive effects of BT, thiamine monophosphate (TMP) and thiamine-a
      compound that is not phosphorylated-were entirely dependent on PAP at the spinal
      level. Moreover, pharmacokinetic studies with wild-type and Pap(-/-) mice
      revealed that PAP is not required for the conversion of BT to thiamine in vivo.
      Taken together, our study highlights an obligatory role for PAP in the
      antinociceptive effects of thiamine and phosphorylated thiamine analogs, and
      suggests a novel phosphatase-independent function for PAP.

PMID- 23119059
TI  - IFN-beta inhibits the increased expression of IL-9 during experimental autoimmune
      uveoretinitis.
AB  - PURPOSE: It has been shown that IL-9 plays a proinflammatory role in the
      pathogenesis of certain autoimmune diseases. This study was designed to
      investigate the possible role of IL-9 in the development of experimental
      autoimmune uveoretinitis (EAU) and the effect of IFN-beta on its expression.
      METHODS: EAU was induced in B10RIII mice by immunization with interphotoreceptor
      retinoid-binding protein peptide 161-180 (IRBP(161-180)). IFN-beta was
      administered subcutaneously to IRBP(161-180) immunized mice every other day from
      day one before immunization to the end of the study. Splenocytes and draining
      lymph node (DLN) cells from EAU mice or control mice or EAU mice treated with IFN
      beta or PBS were stimulated with anti-CD3/CD28 or IRBP(161-180) for 3 days. Naive
      T cells cultured under Th1 or Th17 polarizing conditions were incubated in the
      presence or absence of IFN-beta for 4 days. Effector/memory T cells were
      activated by anti-CD3/CD28 in the presence or absence of IFN-beta for 3 days. IFN
      beta-treated monocytes were cocultured with naive T cells or effector/memory T
      cells for 3 days. Culture supernatants were collected and IL-9 was detected by
      ELISA. RESULTS: IL-9 expression in splenocytes and DLN cells was increased in EAU
      mice during the inflammatory phase and returned back to lower levels during the
      recovery phase. IFN-beta in vivo treatment significantly inhibited EAU activity
      in association with a down-regulated expression of IL-9. In vitro polarized Th1
      and Th17 cells both secreted IL-9 and the addition of IFN-beta suppressed
      production of IL-9 by both Th subsets. Beside its effect on polarized Th cells,
      IFN-beta also suppressed the secretion of IL-9 by effector/memory T cells.
      However, IFN-beta-treated monocytes had no effect on the production of IL-9 when
      cocultured with naive or effector/memory T cells. CONCLUSION: IL-9 expression is
      increased during EAU which could be suppressed by IFN-beta.

PMID- 23119060
TI  - The surname space of the Czech Republic: examining population structure by
      network analysis of spatial co-occurrence of surnames.
AB  - In the majority of countries, surnames represent a ubiquitous cultural attribute
      inherited from an individual's ancestors and predominantly only altered through
      marriage. This paper utilises an innovative method, taken from economics, to
      offer unprecedented insights into the "surname space" of the Czech Republic. We
      construct this space as a network based on the pairwise probabilities of co
      occurrence of surnames and find that the network representation has clear
      parallels with various ethno-cultural boundaries in the country. Our inductive
      approach therefore formalizes a simple assumption that the more frequently the
      bearers of two surnames concentrate in the same locations the higher the
      probability that these two surnames can be related (considering ethno-cultural
      relatedness, common co-ancestry or genetic relatedness, or some other type of
      relatedness). Using the Czech Republic as a case study this paper offers a fresh
      perspective on surnames as a quantitative data source and provides a methodology
      that can be easily incorporated within wider cultural, ethnic, geographic and
      population genetics studies already utilizing surnames.

PMID- 23119061
TI  - Overexpression of osteopontin, alphavbeta3 and Pim-1 associated with
      prognostically important clinicopathologic variables in non-small cell lung
      cancer.
AB  - In this study, we examined the expression of osteopontin (OPN), alphavbeta3 and
      Pim-1 in non-small cell lung cancer (NSCLC) and investigated the potential
      clinical implications of their expression patterns in NSCLC. Immunohistochemical
      assays were used to examine the protein expression of OPN, alphavbeta3 and Pim-1
      in 208 NSCLC samples and their adjacent normal lung tissue specimens. Statistical
      analyses were performed to evaluate the relationships between OPN, alphavbeta3
      and Pim-1 expression patterns, and their association with the clinical
      pathological parameters of NSCLC patients. In NSCLC tissues, the positive rates
      of OPN, alphavbeta3 and Pim-1 expression were 67.8% (141/208), 76.0% (158/208)
      and 58.7% (122/208), respectively. However, in the adjacent normal lung tissues,
      the positive rates of OPN, alphavbeta3 and Pim-1 were 20.2% (42/208), 24.0%
      (50/208) and 14.9% (31/208), respectively. The differences in the positive
      expression rates of OPN, alphavbeta3 and Pim-1 between NSCLCs and the adjacent
      normal lung tissues were all significant (P<0.01). Additionally, the positive
      expression of OPN, alphavbeta3 and Pim-1 in NSCLCs was associated with an
      increase in pathological grade, lymph node metastasis and advanced clinical stage
      (all P<0.01). Furthermore, associations between the expression of OPN and
      alphavbeta3, OPN and Pim-1, and alphavbeta3 and Pim-1 were also observed in our
      NSCLC cohort (all P<0.01). The OPN, alphavbeta3 and Pim-1 proteins are frequently
      overexpressed in NSCLC and are associated with some clinicopathologic variables
      that are of known prognostic importance in NSCLC, suggesting that they may play
      an important role in the development and/or progression of NSCLC.

PMID- 23119063
TI  - Effects of stochasticity in early life history on steepness and population growth
      rate estimates: an illustration on Atlantic bluefin tuna.
AB  - The intrinsic population growth rate (r) of the surplus production function used
      in the biomass dynamic model and the steepness (h) of the stock-recruitment
      relationship used in age-structured population dynamics models are two key
      parameters in fish stock assessment. There is generally insufficient information
      in the data to estimate these parameters that thus have to be constrained. We
      developed methods to directly estimate the probability distributions of r and h
      for the Atlantic bluefin tuna (Thunnus thynnus, Scombridae), using all available
      biological and ecological information. We examined the existing literature to
      define appropriate probability distributions of key life history parameters
      associated with intrinsic growth rate and steepness, paying particular attention
      to the natural mortality for early life history stages. The estimated probability
      distribution of the population intrinsic growth rate was weakly informative, with
      an estimated mean r = 0.77 (+/-0.53) and an interquartile range of (0.34, 1.12).
      The estimated distribution of h was more informative, but also strongly
      asymmetric with an estimated mean h = 0.89 (+/-0.20) and a median of 0.99. We
      note that these two key demographic parameters strongly depend on the
      distribution of early life history mortality rate (M(0)), which is known to
      exhibit high year-to-year variations. This variability results in a widely spread
      distribution of M(0) that affects the distribution of the intrinsic population
      growth rate and further makes the spawning stock biomass an inadequate proxy to
      predict recruitment levels.

PMID- 23119062
TI  - Pericentromeric regions are refractory to prompt repair after replication stress
      induced breakage in HPV16 E6E7-expressing epithelial cells.
AB  - Chromosomal instability is the major form of genomic instability in cancer cells.
      Amongst various forms of chromosomal instability, pericentromeric or centromeric
      instability remains particularly poorly understood. In the present study, we
      found that pericentromeric instability, evidenced by dynamic formation of
      pericentromeric or centromeric rearrangements, breaks, deletions or iso
      chromosomes, was a general phenomenon in human cells immortalized by expression
      of human papillomavirus type 16 E6 and E7 (HPV16 E6E7). In particular, for the
      first time, we surprisingly found a dramatic increase in the proportion of
      pericentromeric chromosomal aberrations relative to total aberrations in HPV16
      E6E7-expressing cells 72 h after release from aphidicolin (APH)-induced
      replication stress, with pericentromeric chromosomal aberrations becoming the
      predominant type of structural aberrations (~70% of total aberrations). In
      contrast, pericentromeric aberrations accounted for only about 20% of total
      aberrations in cells at the end of APH treatment. This increase in relative
      proportion of pericentromeric aberrations after release from APH treatment
      revealed that pericentromeric breaks induced by replication stress are refractory
      to prompt repair in HPV16 E6E7-expressing epithelial cells. Telomerase
      immortalized epithelial cells without HPV16 E6E7 expression did not exhibit such
      preferential pericentromeric instability after release from APH treatment. Cancer
      development is often associated with replication stress. Since HPV16 E6 and E7
      inactivate p53 and Rb, and p53 and Rb pathway defects are common in cancer, our
      finding that pericentromeric regions are refractory to prompt repair after
      replication stress-induced breakage in HPV16 E6E7-expressing cells may shed light
      on mechanism of general pericentromeric instability in cancer.

PMID- 23119064
TI  - A divalent ion is crucial in the structure and dominant-negative function of ID
      proteins, a class of helix-loop-helix transcription regulators.
AB  - Inhibitors of DNA binding and differentiation (ID) proteins, a dominant-negative
      group of helix-loop-helix (HLH) transcription regulators, are well-characterized
      key players in cellular fate determination during development in mammals as well
      as Drosophila. Although not oncogenes themselves, their upregulation by various
      oncogenic proteins (such as Ras, Myc) and their inhibitory effects on cell cycle
      proteins (such as pRb) hint at their possible roles in tumorigenesis.
      Furthermore, their potency as inhibitors of cellular differentiation, through
      their heterodimerization with subsequent inactivation of the ubiquitous E
      proteins, suggest possible novel roles in engineering induced pluripotent stem
      cells (iPSCs). We present the high-resolution 2.1A crystal structure of ID2 (HLH
      domain), coupled with novel biochemical insights in the presence of a divalent
      ion, possibly calcium (Ca2+), in the loop of ID proteins, which appear to be
      crucial for the structure and activity of ID proteins. These new insights will
      pave the way for new rational drug designs, in addition to current synthetic
      peptide options, against this potent player in tumorigenesis as well as more
      efficient ways for stem cells reprogramming.

PMID- 23119065
TI  - CD69 does not affect the extent of T cell priming.
AB  - CD69 is rapidly upregulated on T cells upon activation. In this work we show that
      this is also the case for CD69 expression on dendritic cells (DC). Thus, the
      expression kinetics of CD69 on both cell types is reminiscent of the one of
      costimulatory molecules. Using mouse models of transgenic T cells, we aimed at
      evaluating the effect of monoclonal antibody (MAb)-based targeting and gene
      deficiency of CD69 expressed by either DC or T cells on the extent of antigen
      (Ag)-specific T cell priming, which could be the result of a putative role in
      costimulation as well as on DC maturation and Ag-processing and presentation.
      CD69 targeting or deficiency of DC did not affect their expression of
      costimulatory molecules nor their capacity to induce Ag-specific T cell
      proliferation in in vitro assays. Also, CD69 targeting or deficiency of
      transgenic T cells did not affect the minimal proliferative dose for different
      peptide agonists in vitro. In in vivo models of transgenic T cell transfer and
      local Ag injection, CD69 deficiency of transferred T cells did not affect the
      extent of the proliferative response in Ag-draining lymph nodes (LN). In
      agreement with these results, CD69 MAb targeting or gene deficiency of Vaccinia
      virus (VACV) infected mice did not affect the endogenous formation of virus
      specific CD8(+) T cell populations at the peak of the primary immune response.
      Altogether our results argue against a possible role in costimulation or an
      effect on Ag processing and presentation for CD69.

PMID- 23119067
TI  - Global civil unrest: contagion, self-organization, and prediction.
AB  - Civil unrest is a powerful form of collective human dynamics, which has led to
      major transitions of societies in modern history. The study of collective human
      dynamics, including collective aggression, has been the focus of much discussion
      in the context of modeling and identification of universal patterns of behavior.
      In contrast, the possibility that civil unrest activities, across countries and
      over long time periods, are governed by universal mechanisms has not been
      explored. Here, records of civil unrest of 170 countries during the period 1919
      2008 are analyzed. It is demonstrated that the distributions of the number of
      unrest events per year are robustly reproduced by a nonlinear, spatially extended
      dynamical model, which reflects the spread of civil disorder between geographic
      regions connected through social and communication networks. The results also
      expose the similarity between global social instability and the dynamics of
      natural hazards and epidemics.

PMID- 23119066
TI  - Functional and structural divergence of an unusual LTR retrotransposon family in
      plants.
AB  - Retrotransposons with long terminal repeats (LTRs) more than 3 kb are not
      frequent in most eukaryotic genomes. Rice LTR retrotransposon, Retrosat2, has
      LTRs greater than 3.2 kb and two open reading frames (ORF): ORF1 encodes enzymes
      for retrotransposition whereas no function can be assigned to ORF0 as it is not
      found in any other organism. A variety of experimental and in silico approaches
      were used to determine the origin of Retrosat2 and putative function of ORF0. Our
      data show that not only is Retrosat2 highly abundant in the Oryza genus, it may
      yet be active in rice. Homologs of Retrosat2 were identified in maize, sorghum,
      Arabidopsis and other plant genomes suggesting that the Retrosat2 family is of
      ancient origin. Several putatively cis-acting elements, some multicopy, that
      regulate retrotransposon replication or responsiveness to environmental factors
      were found in the LTRs of Retrosat2. Unlike the ORF1, the ORF0 sequences from
      Retrosat2 and homologs are divergent at the sequence level, 3D-structures and
      predicted biological functions. In contrast to other retrotransposon families,
      Retrosat2 and its homologs are dispersed throughout genomes and not concentrated
      in the specific chromosomal regions, such as centromeres. The genomic
      distribution of Retrosat2 homologs varies across species which likely reflects
      the differing evolutionary trajectories of this retrotransposon family across
      diverse species.

PMID- 23119068
TI  - Fluorescence correlation spectroscopy measurements of the membrane protein TetA
      in Escherichia coli suggest rapid diffusion at short length scales.
AB  - Structural inhomogeneities in biomembranes can lead to complex diffusive behavior
      of membrane proteins that depend on the length or time scales that are probed.
      This effect is well studied in eukaryotic cells, but has been explored only
      recently in bacteria. Here we used fluorescence recovery after photobleaching
      (FRAP) and fluorescence correlation spectroscopy (FCS) to study diffusion of the
      membrane protein TetA-YFP in E. coli. We find that the diffusion constant
      determined from FRAP is comparable to other reports of inner membrane protein
      diffusion constants in E. coli. However, FCS, which probes diffusion on shorter
      length scales, gives a value that is almost two orders of magnitude higher and is
      comparable to lipid diffusion constants. These results suggest there is a
      population of TetA-YFP molecules in the membrane that move rapidly over short
      length scales (~ 400 nm) but move significantly more slowly over the longer
      length scales probed by FRAP.

PMID- 23119069
TI  - A population-based study of gastroesophageal reflux disease and sleep problems in
      elderly twins.
AB  - BACKGROUND & AIMS: Previous studies indicate an association between sleep
      problems and gastroesophageal reflux disease (GERD). Although both these
      conditions separately have moderate heritabilities, confounding by genetic
      factors has not previously been taken into account. This study aimed to reveal
      the association between sleep problems and GERD, while adjusting for heredity and
      other potential confounding factors. METHODS: This cross-sectional population
      based study included all 8,014 same-sexed twins of at least 65 years of age and
      born in Sweden between 1886 and 1958, who participated in telephone interviews in
      1998-2002. Three logistic regression models were used 1) external control
      analysis, 2) within-pair co-twin analysis with dizygotic (DZ) twin pairs
      discordant for GERD, and 3) within-pair co-twin analysis with monozygotic (MZ)
      twin pairs discordant for GERD. Odds ratios (ORs) with 95% confidence intervals
      (CIs) were calculated and adjusted for established risk factors for GERD, i.e.
      sex, age, body mass index (BMI), tobacco smoking, and educational level. RESULTS:
      A dose-response association was identified between increasing levels of sleep
      problems and GERD in the external control analysis. Individuals who often
      experienced sleep problems had a two-fold increased occurrence of GERD compared
      to those who seldom had sleep problems (OR 2.0, 95% CI 1.8-2.4). The
      corresponding association was of similar strength in the co-twin analysis
      including 356 DZ pairs (OR 2.2, 95% CI 1.6-3.4), and in the co-twin analysis
      including 210 MZ pairs (OR 1.5, 95% CI 0.9-2.7). CONCLUSION: A dose-dependent
      association between sleep problems and GERD remains after taking heredity and
      other known risk factors for GERD into account.

PMID- 23119070
TI  - The repetitive domain of ScARP3d triggers entry of Spiroplasma citri into
      cultured cells of the vector Circulifer haematoceps.
AB  - Spiroplasma citri is a plant pathogenic mollicute transmitted by the leafhopper
      vector Circulifer haematoceps. Successful transmission requires the spiroplasmas
      to cross the intestinal epithelium and salivary gland barriers through
      endocytosis mediated by receptor-ligand interactions. To characterize these
      interactions we studied the adhesion and invasion capabilities of a S. citri
      mutant using the Ciha-1 leafhopper cell line. S. citri GII3 wild-type contains 7
      plasmids, 5 of which (pSci1 to 5) encode 8 related adhesins (ScARPs). As compared
      to the wild-type strain GII3, the S. citri mutant G/6 lacking pSci1 to 5 was
      affected in its ability to adhere and enter into the Ciha-1 cells. Proteolysis
      analyses, Triton X-114 partitioning and agglutination assays showed that the N
      terminal part of ScARP3d, consisting of repeated sequences, was exposed to the
      spiroplasma surface whereas the C-terminal part was anchored into the membrane.
      Latex beads cytadherence assays showed the ScARP3d repeat domain (Rep3d) to be
      involved, and internalization of the Rep3d-coated beads to be actin-dependent.
      These data suggested that ScARP3d, via its Rep3d domain, was implicated in
      adhesion of S. citri GII3 to insect cells. Inhibition tests using anti-Rep3d
      antibodies and competitive assays with recombinant Rep3d both resulted in a
      decrease of insect cells invasion by the spiroplasmas. Unexpectedly, treatment of
      Ciha-1 cells with the actin polymerisation inhibitor cytochalasin D increased
      adhesion and consequently entry of S. citri GII3. For the ScARPs-less mutant G/6,
      only adhesion was enhanced though to a lesser extent following cytochalasin D
      treatment. All together these results strongly suggest a role of ScARPs, and
      particularly ScARP3d, in adhesion and invasion of the leafhopper cells by S.
      citri.

PMID- 23119071
TI  - C. difficile 630Deltaerm Spo0A regulates sporulation, but does not contribute to
      toxin production, by direct high-affinity binding to target DNA.
AB  - Clostridium difficile is a Gram positive, anaerobic bacterium that can form
      highly resistant endospores. The bacterium is the causative agent of C. difficile
      infection (CDI), for which the symptoms can range from a mild diarrhea to
      potentially fatal pseudomembranous colitis and toxic megacolon. Endospore
      formation in Firmicutes, including C. difficile, is governed by the key regulator
      for sporulation, Spo0A. In Bacillus subtilis, this transcription factor is also
      directly or indirectly involved in various other cellular processes. Here, we
      report that C. difficile Spo0A shows a high degree of similarity to the well
      characterized B. subtilis protein and recognizes a similar binding sequence. We
      find that the laboratory strain C. difficile 630Deltaerm contains an 18bp
      duplication near the DNA-binding domain compared to its ancestral strain 630. In
      vitro binding assays using purified C-terminal DNA binding domain of the C.
      difficile Spo0A protein demonstrate direct binding to DNA upstream of spo0A and
      sigH, early sporulation genes and several other putative targets. In vitro
      binding assays suggest that the gene encoding the major clostridial toxin TcdB
      may be a direct target of Spo0A, but supernatant derived from a spo0A negative
      strain was no less toxic towards Vero cells than that obtained from a wild type
      strain, in contrast to previous reports. These results identify for the first
      time direct (putative) targets of the Spo0A protein in C. difficile and make a
      positive effect of Spo0A on production of the large clostridial toxins unlikely.

PMID- 23119074
TI  - Partial complementarity of the mimetic yellow bar phenotype in Heliconius
      butterflies.
AB  - Heliconius butterflies are an excellent system for understanding the genetic
      basis of phenotypic change. Here we document surprising diversity in the genetic
      control of a common phenotype. Two disjunct H. erato populations have each
      recruited the Cr and/or Sd loci that control similar yellow hindwing patterns,
      but the alleles involved partially complement one another indicating either
      multiple origins for the patterning alleles or developmental drift in genetic
      control of similar patterns. We show that in these H. erato populations cr and sd
      are epistatically interacting and that the parental origin of alleles can explain
      phenotypes of backcross individuals. In contrast, mimetic H. melpomene
      populations with identical phenotypes (H. m. rosina and H. m. amaryllis) do not
      show genetic complementation (F(1)s and F(2)s are phenotypically identical to
      parentals). Finally, we report hybrid female inviability in H. m. melpomene * H.
      m. rosina crosses (previously only female infertility had been reported) and
      presence of standing genetic variation for alternative color alleles at the Yb
      locus in true breeding H. melpomene melpomene populations (expressed when in a
      different genomic background) that could be an important source of variation for
      the evolution of novel phenotypes or a result of developmental drift. Although
      recent work has emphasized the simple genetic control of wing pattern in
      Heliconius, we show there is underlying complexity in the allelic variation and
      epistatic interactions between major patterning loci.

PMID- 23119073
TI  - Mental rotation performance in male soccer players.
AB  - It is the main goal of this study to investigate the visual-spatial cognition in
      male soccer players. Forty males (20 soccer players and 20 non-athletes) solved a
      chronometric mental rotation task with both cubed and embodied figures (human
      figures, body postures). The results confirm previous results that all
      participants had a lower mental rotation speed for cube figures compared to
      embodied figures and a higher error rate for cube figures, but only at angular
      disparities greater than 90 degrees . It is a new finding that soccer-players
      showed a faster reaction time for embodied stimuli. Because rotation speed did
      not differ between soccer-players and non-athletes this finding cannot be
      attributed to the mental rotation process itself but instead to differences in
      one of the following processes which are involved in a mental rotation task: the
      encoding process, the maintanence of readiness, or the motor process. The results
      are discussed against the background of the influence on longterm physical
      activity on mental rotation and the context of embodied cognition.

PMID- 23119072
TI  - Serum retinol-binding protein 4 as a marker for cardiovascular disease in women.
AB  - BACKGROUND: Elevated serum level of retinol-binding protein 4 (RBP4) has been
      associated with obesity-related co-morbidities including insulin resistance,
      dyslipidemia and hypertension. OBJECTIVES: The present study examined the
      relationship between serum level of RBP4 and various risk factors related to
      cardiovascular disease (CVD) in men and women. METHODS: 284 subjects (139 males,
      145 females), grouped into healthy (n = 60), obese diabetes (n = 60), non-obese
      diabetes (n = 60), obese non-diabetes (n = 60) and patients with CVD (n = 44),
      were assessed for anthropometric and biochemical parameters related to obesity,
      diabetes and CVD. In addition, serum levels of several adipokines, including
      fatty acid binding protein 4 (FABP4) and lipocalin 2 (LCN2) and RBP4 were
      measured using specific immunoassays. RESULTS: Serum RBP4 level correlated
      significantly with principal component derived from known risk factors of CVD
      (beta = 0.20+/-0.06, P = 0.002). Significance of this correlation was limited to
      women (beta = 0.20+/-0.06, P = 0.002) and it persisted even after adjusting for
      BMI (beta = 0.19+/-0.06, P = 0.002). Overall (n = 284) serum RBP4 values
      significantly correlated with FABP4 (R = 0.19, p = 0.001). Serum FABP4 level of
      CVD subjects was significantly higher than healthy control (P = 0.001) and non
      obese diabetes (P = 0.04) groups, but this difference was attributable to
      differences in BMI. Serum LCN2 level correlated well with RBP4 (R = 0.15, P =
      0.008) and FABP4 (R = 0.36, P<0.001), but did not differ significantly between
      CVD and other groups. CONCLUSIONS: Results of this study indicate a significant
      correlation between serum RBP4 and various established risk factors for CVD and
      suggest RBP4 may serve as an independent predictor of CVD in women.

PMID- 23119076
TI  - Towards improvements in the estimation of the coalescent: implications for the
      most effective use of Y chromosome short tandem repeat mutation rates.
AB  - Over the past two decades, many short tandem repeat (STR) microsatellite loci on
      the human Y chromosome have been identified together with mutation rate estimates
      for the individual loci. These have been used to estimate the coalescent age, or
      the time to the most recent common ancestor (TMRCA) expressed in generations, in
      conjunction with the average square difference measure (ASD), an unbiased point
      estimator of TMRCA based upon the average within-locus allele variance between
      haplotypes. The ASD estimator, in turn, depends on accurate mutation rate
      estimates to be able to produce good approximations of the coalescent age of a
      sample. Here, a comparison is made between three published sets of per locus
      mutation rate estimates as they are applied to the calculation of the coalescent
      age for real and simulated population samples. A novel evaluation method is
      developed for estimating the degree of conformity of any Y chromosome STR locus
      of interest to the strict stepwise mutation model and specific recommendations
      are made regarding the suitability of thirty-two commonly used Y-STR loci for the
      purpose of estimating the coalescent. The use of the geometric mean for averaging
      ASD and u across loci is shown to improve the consistency of the resulting
      estimates, with decreased sensitivity to outliers and to the number of STR loci
      compared or the particular set of mutation rates selected.

PMID- 23119075
TI  - Immobilized metal affinity chromatography co-purifies TGF-beta1 with histidine
      tagged recombinant extracellular proteins.
AB  - Extracellular recombinant proteins are commonly produced using HEK293 cells as
      histidine-tagged proteins facilitating purification by immobilized metal affinity
      chromatography (IMAC). Based on gel analyses, this one-step purification
      typically produces proteins of high purity. Here, we analyzed the presence of TGF
      beta1 in such IMAC purifications using recombinant extracellular fibrillin-1
      fragments as examples. Analysis of various purified recombinant fibrillin-1
      fragments by ELISA consistently revealed the presence of picomolar concentrations
      of active and latent TGF-beta1, but not of BMP-2. These quantities of TGF-beta1
      were not detectable by Western blotting and mass spectrometry. However, the
      amounts of TGF-beta1 were sufficient to consistently trigger Smad2
      phosphorylation in fibroblasts. The purification mechanism was analyzed to
      determine whether the presence of TGF-beta1 in these protein preparations
      represents a specific or non-specific co-purification of TGF-beta1 with fibrillin
      1 fragments. Control purifications using conditioned medium from non-transfected
      293 cells yielded similar amounts of TGF-beta1 after IMAC. IMAC of purified TGF
      beta1 and the latency associated peptide showed that these proteins bound to the
      immobilized nickel ions. These data clearly demonstrate that TGF-beta1 was co
      purified by specific interactions with nickel, and not by specific interactions
      with fibrillin-1 fragments. Among various chromatographic methods tested for
      their ability to eliminate TGF-beta1 from fibrillin-1 preparations, gel
      filtration under high salt conditions was highly effective. As various
      recombinant extracellular proteins purified in this fashion are frequently used
      for experiments that can be influenced by the presence of TGF-beta1, these
      findings have far-reaching implications for the required chromatographic schemes
      and quality controls.

PMID- 23119077
TI  - Clinical preventive services in Guatemala: a cross-sectional survey of internal
      medicine physicians.
AB  - BACKGROUND: Guatemala is currently undergoing an epidemiologic transition.
      Preventive services are key to reducing the burden of non-communicable diseases,
      and smoking counseling and cessation are among the most cost-effective and wide
      reaching strategies. Internal medicine physicians are fundamental to providing
      such services, and their knowledge is a cornerstone of non-communicable disease
      control. METHODS: A national cross-sectional survey was conducted in 2011 to
      evaluate knowledge of clinical preventive services for non-communicable diseases.
      Interns, residents, and attending physicians of the internal medicine departments
      of all teaching hospitals in Guatemala completed a self-administered
      questionnaire. Participants' responses were contrasted with the Guatemalan
      Ministry of Health (MoH) prevention guidelines and the US Preventive Services
      Task Force (USPSTF) recommendations. Analysis compared knowledge of
      recommendations within and between hospitals. RESULTS: In response to simulated
      patient scenarios, all services were recommended by more than half of physicians
      regardless of MoH or USPSTF recommendations. Prioritization was adequate
      according to the MoH guidelines but not including other potentially effective
      services (e.g. colorectal cancer and lipid disorder screenings). With the
      exception of colorectal and prostate cancer screening, less frequently
      recommended by interns, there was no difference in recommendation rates by level.
      CONCLUSION: Guatemalan internal medicine physicians' knowledge on preventive
      services recommendations for non-communicable diseases is limited, and
      prioritization did not reflect cost-effectiveness. Based on these data we
      recommend that preventive medicine training be strengthened and development of
      evidence-based guidelines for low-middle income countries be a priority.

PMID- 23119078
TI  - Alcohol affects the brain's resting-state network in social drinkers.
AB  - Acute alcohol intake is known to enhance inhibition through facilitation of
      GABA(A) receptors, which are present in 40% of the synapses all over the brain.
      Evidence suggests that enhanced GABAergic transmission leads to increased large
      scale brain connectivity. Our hypothesis is that acute alcohol intake would
      increase the functional connectivity of the human brain resting-state network
      (RSN). To test our hypothesis, electroencephalographic (EEG) measurements were
      recorded from healthy social drinkers at rest, during eyes-open and eyes-closed
      sessions, after administering to them an alcoholic beverage or placebo
      respectively. Salivary alcohol and cortisol served to measure the inebriation and
      stress levels. By calculating Magnitude Square Coherence (MSC) on standardized
      Low Resolution Electromagnetic Tomography (sLORETA) solutions, we formed cortical
      networks over several frequency bands, which were then analyzed in the context of
      functional connectivity and graph theory. MSC was increased (p<0.05, corrected
      with False Discovery Rate, FDR corrected) in alpha, beta (eyes-open) and theta
      bands (eyes-closed) following acute alcohol intake. Graph parameters were
      accordingly altered in these bands quantifying the effect of alcohol on the
      structure of brain networks; global efficiency and density were higher and path
      length was lower during alcohol (vs. placebo, p<0.05). Salivary alcohol
      concentration was positively correlated with the density of the network in beta
      band. The degree of specific nodes was elevated following alcohol (vs. placebo).
      Our findings support the hypothesis that short-term inebriation considerably
      increases large-scale connectivity in the RSN. The increased baseline functional
      connectivity can -at least partially- be attributed to the alcohol-induced
      disruption of the delicate balance between inhibitory and excitatory
      neurotransmission in favor of inhibitory influences. Thus, it is suggested that
      short-term inebriation is associated, as expected, to increased GABA transmission
      and functional connectivity, while long-term alcohol consumption may be linked to
      exactly the opposite effect.

PMID- 23119080
TI  - Hyperferritinemia and hyperuricemia may be associated with liver function
      abnormality in obese adolescents.
AB  - BACKGROUND: The iron status in human body and its association with liver function
      in adolescents was rarely studied. The objective was to investigate the
      association among the levels of serum ferritin, uric acid and alanine
      aminotransferase (ALT) in adolescents. METHODS AND RESULTS: A total of 2090
      adolescents negative for hepatitis B surface antigen from one junior high school
      (786, 12-13 years), three senior high schools (973, 15-16 years) and one college
      (331, 18-19 years) participated in this survey. Anthropometric and biochemical
      measurements, including complete blood count, ALT, serum ferritin and uric acid
      were performed. An ALT>42 U/L was defined as elevated, a ferritin level >200 ug/L
      was defined as hyperferritinemia. A uric acid level >460 umol/L in males and >340
      umol/L in females was defined as hyperuricemia. The chi-squared test, linear
      regression and multivariate logistic regression were used for the data analysis.
      Elevated ALT levels were detected in 76 (3.6%) students and were more prevalent
      in males than females (6.4% vs. 2.0%, p<0.001). The univariate analysis found
      gender, age group, body mass index, ferritin level, uric acid level and white
      blood cell count all to be significantly associated with elevated ALT. Linear
      regression showed a positive correlation among log(ferritin), uric acid level and
      ALT level. Elevated ALT occurred more frequently at ferritin level >100 ug/L. The
      logistic regression analysis found that body mass index, hyperferritinemia and
      hyperuricemia were significant factors associated with the ALT elevation, but
      gender, age, and white blood cell count were not. CONCLUSIONS: Hyperferritinemia
      and hyperuricemia are two independently significant factors associated with ALT
      elevation among obese adolescents. More studies are needed to corroborate any
      hypothesis related to these phenomena.

PMID- 23119079
TI  - Adipocyte dysfunction in a mouse model of polycystic ovary syndrome (PCOS):
      evidence of adipocyte hypertrophy and tissue-specific inflammation.
AB  - Clinical research shows an association between polycystic ovary syndrome (PCOS)
      and chronic inflammation, a pathological state thought to contribute to insulin
      resistance. The underlying pathways, however, have not been defined. The purpose
      of this study was to characterize the inflammatory state of a novel mouse model
      of PCOS. Female mice lacking leptin and insulin receptors in pro-opiomelanocortin
      neurons (IR/LepR(POMC) mice) and littermate controls were evaluated for estrous
      cyclicity, ovarian and adipose tissue morphology, and body composition by QMR and
      CT scan. Tissue-specific macrophage infiltration and cytokine mRNA expression
      were measured, as well as circulating cytokine levels. Finally, glucose
      regulation during pregnancy was evaluated as a measure of risk for diabetes
      development. Forty-five percent of IR/LepR(POMC) mice showed reduced or absent
      ovulation. IR/LepR(POMC) mice also had increased fat mass and adipocyte
      hypertrophy. These traits accompanied elevations in macrophage accumulation and
      inflammatory cytokine production in perigonadal adipose tissue, liver, and ovary.
      These mice also exhibited gestational hyperglycemia as predicted. This report is
      the first to show the presence of inflammation in IR/LepR(POMC) mice, which
      develop a PCOS-like phenotype. Thus, IR/LepR(POMC) mice may serve as a new mouse
      model to clarify the involvement of adipose and liver tissue in the pathogenesis
      and etiology of PCOS, allowing more targeted research on the development of PCOS
      and potential therapeutic interventions.

PMID- 23119081
TI  - CYP24A1 exacerbated activity during diabetes contributes to kidney tubular
      apoptosis via caspase-3 increased expression and activation.
AB  - Decreases in circulating 25,hydroxyl-vitamin D3 (25 OH D3) and 1,25,dihydroxyl
      vitamin D3 (1,25 (OH)2 D3) have been extensively documented in patients with type
      2 diabetes. Nevertheless, the molecular reasons behind this drop, and whether it
      is a cause or an effect of disease progression is still poorly understood. With
      the skin and the liver, the kidney is one of the most important sites for vitamin
      D metabolism. Previous studies have also shown that CYP24A1 (an enzyme implicated
      in vitamin D metabolism), might play an important role in furthering the
      progression of kidney lesions during diabetic nephropathy. In this study we show
      a link between CYP24A1 increase and senescence followed by apoptosis induction in
      the renal proximal tubules of diabetic kidneys. We show that CYP24A1 expression
      was increased during diabetic nephropathy progression. This increase derived from
      protein kinase C activation and increased H(2)O(2) cellular production. CYP24A1
      increase had a major impact on cellular phenotype, by pushing cells into
      senescence, and later into apoptosis. Our data suggest that control of CYP24A1
      increase during diabetes has a beneficial effect on senescence induction and
      caspase-3 increased expression. We concluded that diabetes induces an increase in
      CYP24A1 expression, destabilizing vitamin D metabolism in the renal proximal
      tubules, leading to cellular instability and apoptosis, and thereby accelerating
      tubular injury progression during diabetic nephropathy.

PMID- 23119083
TI  - Plasmacytoid dendritic cells play a role for effective innate immune responses
      during Chlamydia pneumoniae infection in mice.
AB  - Plasmacytoid dendritic cells (pDCs) are known for their robust antiviral response
      and their pro-tolerance effects towards allergic diseases and tissue
      engraftments. However, little is known about the role pDCs may play during a
      bacterial infection, including pulmonary Chlamydia pneumoniae (CP). In this
      study, we investigated the role of pDCs during pulmonary CP infection. Our
      results revealed that depletion of pDCs during acute CP infection in mice results
      in delayed and reduced lung inflammation, with an early delay in cellular
      recruitment and significant reduction in early cytokine production in the lungs.
      This was followed by impaired and delayed bacterial clearance from the lungs
      which then resulted in a severe and prolonged chronic inflammation and iBALT like
      structures containing large numbers of B and T cells in these animals. We also
      observed that increasing the pDC numbers in the lung by FLT3L treatment
      experimentally results in greater lung inflammation during acute CP infection. In
      contrast to these results, restimulation of T-cells in the draining lymph nodes
      of pDC-depleted mice induced greater amounts of proinflammatory cytokines than we
      observed in control mice. These results suggest that pDCs in the lung may provide
      critical proinflammatory innate immune responses in response to CP infection, but
      are suppressive towards adaptive immune responses in the lymph node. Thus pDCs in
      the lung and the draining lymph node appear to have different roles and
      phenotypes during acute CP infection and may play a role in host immune
      responses.

PMID- 23119082
TI  - Close interactions between mesenchymal stem cells and neuroblastoma cell lines
      lead to tumor growth inhibition.
AB  - Mesenchymal stem cells (MSCs) have attracted much interest in oncology since they
      exhibit marked tropism for the tumor microenvironment and support or suppress
      malignant cell growth depending on the tumor model tested. The aim of this study
      was to investigate the role of MSCs in the control of the growth of neuroblastoma
      (NB), which is the second most common solid tumor in children. In vivo
      experiments showed that systemically administered MSCs, under our experimental
      conditions, did not home to tumor sites and did not affect tumor growth or
      survival. However, MSCs injected intratumorally in an established subcutaneous NB
      model reduced tumor growth through inhibition of proliferation and induction of
      apoptosis of NB cells and prolonged the survival of hMSC-treated mice. The need
      for contact between MSCs and NB cells was further supported by in vitro
      experiments. In particular, MSCs were found to be attracted by NB cells, and to
      affect NB cell proliferation with different results depending on the cell line
      tested. Moreover, NB cells, after pre-incubation with hMSCs, acquired a more
      invasive behavior towards CXCL12 and the bone marrow, i.e., the primary site of
      NB metastases. In conclusion, this study demonstrates that functional cross-talk
      between MSCs and NB cell lines used in our experiments can occur only within
      short range interaction. Thus, this report does not support the clinical use of
      MSCs as vehicles for selective delivery of antitumor drugs at the NB site unless
      chemotherapy and/or radiotherapy create suitable local conditions for MSCs
      recruitment.

PMID- 23119084
TI  - Amplitude of low-frequency oscillations in first-episode, treatment-naive
      patients with major depressive disorder: a resting-state functional MRI study.
AB  - BACKGROUND: Resting-state fMRI is a novel approach to measure spontaneous brain
      activity in patients with major depressive disorder (MDD). Although most resting
      state fMRI studies have focused on the examination of temporal correlations
      between low-frequency oscillations (LFOs), few studies have explored the
      amplitude of these LFOs in MDD. In this study, we applied the approaches of
      amplitude of low-frequency fluctuation (ALFF) and fractional ALFF to examine the
      amplitude of LFOs in MDD. METHODOLOGY/PRINCIPAL FINDINGS: A total of 36 subjects,
      18 first-episode, treatment-naive patients with MDD matched with 18 healthy
      controls (HCs) completed the fMRI scans. Compared with HCs, MDD patients showed
      increased ALFF in the right fusiform gyrus and the right anterior and posterior
      lobes of the cerebellum but decreased ALFF in the left inferior temporal gyrus,
      bilateral inferior parietal lobule, and right lingual gyrus. The fALFF in
      patients was significantly increased in the right precentral gyrus, right
      inferior temporal gyrus, bilateral fusiform gyrus, and bilateral anterior and
      posterior lobes of the cerebellum but was decreased in the left dorsolateral
      prefrontal cortex, bilateral medial orbitofrontal cortex, bilateral middle
      temporal gyrus, left inferior temporal gyrus, and right inferior parietal lobule.
      After taking gray matter (GM) volume as a covariate, the results still remained.
      CONCLUSIONS/SIGNIFICANCE: These findings indicate that MDD patients have altered
      LFO amplitude in a number of regions distributed over the frontal, temporal,
      parietal, and occipital cortices and the cerebellum. These aberrant regions may
      be related to the disturbances of multiple emotion- and cognition-related
      networks observed in MDD and the apparent heterogeneity in depressive symptom
      domains. Such brain functional alteration of MDD may contribute to further
      understanding of MDD-related network imbalances demonstrated in previous fMRI
      studies.

PMID- 23119085
TI  - Culture conditions affect cardiac differentiation potential of human pluripotent
      stem cells.
AB  - Human pluripotent stem cells (hPSCs), including human embryonic stem cells
      (hESCs) and human induced pluripotent stem cells (hiPSCs), are capable of
      differentiating into any cell type in the human body and thus can be used in
      studies of early human development, as cell models for different diseases and
      eventually also in regenerative medicine applications. Since the first derivation
      of hESCs in 1998, a variety of culture conditions have been described for the
      undifferentiated growth of hPSCs. In this study, we cultured both hESCs and
      hiPSCs in three different culture conditions: on mouse embryonic fibroblast (MEF)
      and SNL feeder cell layers together with conventional stem cell culture medium
      containing knockout serum replacement and basic fibroblast growth factor (bFGF),
      as well as on a Matrigel matrix in mTeSR1 medium. hPSC lines were subjected to
      cardiac differentiation in mouse visceral endodermal-like (END-2) co-cultures and
      the cardiac differentiation efficiency was determined by counting both the
      beating areas and Troponin T positive cells, as well as studying the expression
      of OCT-3/4, mesodermal Brachyury T and NKX2.5 and endodermal SOX-17 at various
      time points during END-2 differentiation by q-RT-PCR analysis. The most efficient
      cardiac differentiation was observed with hPSCs cultured on MEF or SNL feeder
      cell layers in stem cell culture medium and the least efficient cardiac
      differentiation was observed on a Matrigel matrix in mTeSR1 medium. Further,
      hPSCs cultured on a Matrigel matrix in mTeSR1 medium were found to be more
      committed to neural lineage than hPSCs cultured on MEF or SNL feeder cell layers.
      In conclusion, culture conditions have a major impact on the propensity of the
      hPSCs to differentiate into a cardiac lineage.

PMID- 23119086
TI  - Variants identified in a GWAS meta-analysis for blood lipids are associated with
      the lipid response to fenofibrate.
AB  - A recent large-scale meta-analysis of genome-wide studies has identified 95 loci,
      59 of them novel, as statistically significant predictors of blood lipid traits;
      we tested whether the same loci explain the observed heterogeneity in response to
      lipid-lowering therapy with fenofibrate. Using data from the Genetics of Lipid
      Lowering Drugs and Diet Network (GOLDN, n = 861) we fit linear mixed models with
      the genetic markers as predictors and high-density lipoprotein (HDL) cholesterol,
      low-density lipoprotein (LDL) cholesterol, total cholesterol, and triglyceride
      concentrations as outcomes. For all four traits, we analyzed both baseline levels
      and changes in response to treatment with fenofibrate. For the markers that were
      significantly associated with fenofibrate response, we fit additional models
      evaluating potential epistatic interactions. All models were adjusted for age,
      sex, and study center as fixed effects, and pedigree as a random effect.
      Statistically significant associations were observed between the rs964184
      polymorphism near APOA1 (P-value<=0.0001) and fenofibrate response for HDL and
      triglycerides. The association was replicated in the Pharmacogenetics of
      Hypertriglyceridemia in Hispanics study (HyperTG, n = 267). Suggestive
      associations with fenofibrate response were observed for markers in or near
      PDE3A, MOSC1, FLJ36070, CETP, the APOE-APOC1-APOC4-APOC2, and CILP2. Finally, we
      present strong evidence for epistasis (P-value for interaction =  0.0006 in
      GOLDN, 0.05 in HyperTG) between rs10401969 near CILP2 and rs4420638 in the APOE
      APOC1-APOC4-APOC2 cluster with total cholesterol response to fenofibrate. In
      conclusion, we present evidence linking several novel and biologically relevant
      genetic polymorphisms to lipid lowering drug response, as well as suggesting
      novel gene-gene interactions in fenofibrate pharmacogenetics.

PMID- 23119087
TI  - Comprehensive knowledge of HIV among women in rural Mozambique: development and
      validation of the HIV knowledge 27 scale.
AB  - BACKGROUND: The relationship between HIV knowledge and HIV-related behaviors in
      settings like Mozambique has been limited by a lack of rigorously validated
      measures. METHODS: A convenience sample of women seeking prenatal care at two
      clinics were administered an adapted, orally-administered, 27 item HIV-knowledge
      scale, the HK-27. Validation analyses were stratified by survey language
      (Portuguese and Echuabo). Kuder-Richardson (KR-20) coefficients estimated
      internal reliability. Construct validity was assessed with bivariate associations
      between HK-27 scores (% correct) and selected participant characteristics. The
      association between knowledge, self-reported HIV testing, and HIV infection were
      evaluated with multivariable logistic regression. RESULTS: Participants (N = 348)
      had a median age of 24; 188 spoke Portuguese, and 160 spoke Echuabo. Mean HK-27
      scores were higher for Portuguese-speaking participants than Echuabo-speaking
      participants (68% correct vs. 42%, p<0.001). Internal reliability was strong (KR
      20>0.8) for scales in both languages. Higher HK-27 scores were significantly
      (p<=0.05) correlated with more education, more media items in the home, a history
      of HIV testing, and participant work outside of the home for women of both
      languages. HK-27 scores were independently associated with completion of HIV
      testing in multivariable analysis (per 1% correct: aOR:1.02, 95%CI:0.01-0.03, p =
      0.01), but not with HIV infection. CONCLUSIONS: HK-27 is a reliable and valid
      measure of HIV knowledge among Portuguese and Echuabo-speaking Mozambican women.
      The HK-27 demonstrated significant knowledge deficits among women in the study,
      and higher scores were associated with higher HIV testing probability. Future
      studies should evaluate the role of the HK-27 in longitudinal studies and in
      other populations.

PMID- 23119088
TI  - State-related changes in MEG functional connectivity reveal the task-positive
      sensorimotor network.
AB  - Functional connectivity measures applied to magnetoencephalography (MEG) data
      have the capacity to elucidate neuronal networks. However, the task-related
      modulation of these measures is essential to identifying the functional relevance
      of the identified network. In this study, we provide evidence for the efficacy of
      measuring "state-related" (i.e., task vs. rest) changes in MEG functional
      connectivity for revealing a sensorimotor network. We investigate changes in
      functional connectivity, measured as cortico-cortical coherence (CCC), between
      rest blocks and the performance of a visually directed motor task in a healthy
      cohort. Task-positive changes in CCC were interpreted in the context of any
      concomitant modulations in spectral power. Task-related increases in whole-head
      CCC relative to the resting state were identified between areas established as
      part of the sensorimotor network as well as frontal eye fields and prefrontal
      cortices, predominantly in the beta and gamma frequency bands. This study
      provides evidence for the use of MEG to identify task-specific functionally
      connected sensorimotor networks in a non-invasive, patient friendly manner.

PMID- 23119089
TI  - Autoregulation of RNA helicase expression in response to temperature stress in
      Synechocystis sp. PCC 6803.
AB  - RNA helicases are ubiquitous enzymes whose modification of RNA secondary
      structure is known to regulate RNA function. The pathways controlling RNA
      helicase expression, however, have not been well characterized. Expression of the
      cyanobacterial RNA helicase, crhR, is regulated in response to environmental
      signals that alter the redox poise of the electron transport chain, including
      light and temperature. Here we analyze crhR expression in response to alteration
      of abiotic conditions in wild type and a crhR mutant, providing evidence that
      CrhR autoregulates its own expression through a combination of transcriptional
      and post-transcriptional mechanisms. Temperature regulates crhR expression
      through alteration of both transcript and protein half-life which are
      significantly extended at low temperature (20 degrees C). CrhR-dependent
      mechanisms regulate both the transient accumulation of crhR transcript at 20
      degrees C and stability of the CrhR protein at all temperatures. CrhR-independent
      mechanisms regulate temperature sensing and induction of crhR transcript
      accumulation at 20 degrees C and the temperature regulation of crhR transcript
      stability, suggesting CrhR is not directly associated with crhR mRNA turnover.
      Many of the processes are CrhR- and temperature-dependent and occur in the
      absence of a correlation between crhR transcript and protein abundance. The data
      provide important insights into not only how RNA helicase gene expression is
      regulated but also the role that rearrangement of RNA secondary structure
      performs in the molecular response to temperature stress. We propose that the
      crhR-regulatory pathway exhibits characteristics similar to the heat shock
      response rather than a cold stress-specific mechanism.

PMID- 23119090
TI  - Seroprevalence of pertussis in Senegal: a prospective study.
AB  - BACKGROUND: Pertussis, also known as whooping cough, is a vaccine-preventable
      respiratory disease caused by Bordetella pertussis infection, against which
      Senegalese children are immunized with the diphtheria-tetanus-whole cell
      pertussis vaccine (DTwP). Seroepidemiology of pertussis has been widely described
      in industrialized countries, but rare are the studies referring to it in
      developing countries. METHODS: We conducted a longitudinal survey in Northern
      Senegal to investigate the epidemiology of B. pertussis by evaluating the IgG
      antibody (Ab) response against pertussis toxin (PT). A cohort of 410 children
      aged 1 to 9 from five villages in the Middle Senegal River Valley were followed
      up for 18 months. During that period, five visits were made to assess the
      immunological status of the children. PRINCIPAL FINDINGS: PT-specific IgG
      responses were significantly different according to age. Until the age of 3,
      there was a decrease in the Ab response, which then increased in the older
      groups. Assessment of IgG antibodies to PT (IgG-PT) suggested evidence of recent
      exposures to the pathogen. Surprisingly, in one of the five villages the average
      Ab response to PT was very low at all ages during the first 6 months of the
      study. At the third visit, IgG-PT concentrations peaked to very high levels, to
      slightly decline at the end of the survey. This indicates an outbreak of B.
      pertussis, whereas in the other villages a pertussis endemic profile could be
      observed. CONCLUSIONS: Pertussis is endemic in Northern Senegal despite the
      introduction of vaccination. The circulation of the bacteria seems to differ
      between geographic locations and over time. A more complete understanding of the
      epidemiology of pertussis and its environmental determinants could provide
      information to adapt vaccination programs.

PMID- 23119092
TI  - Morph matters: aggression bias in a polymorphic sparrow.
AB  - In species with discrete morphs exhibiting alternative behavioral strategies,
      individuals may vary their aggressive behavior in competitive encounters
      according to the phenotype of their opponent. Such aggression bias has been
      documented in multiple polymorphic species evolving under negative frequency
      dependent selection, but it has not been well-studied under other selection
      regimes. We investigated this phenomenon in white-throated sparrows (Zonotrichia
      albicollis), a passerine with plumage polychromatism maintained by disassortative
      mating. The two distinct color morphs differ with respect to reproductive
      strategy in that white-striped birds invest more in territorial aggression than
      tan-striped birds. Whether territorial aggression in this species is biased
      according to the morph of an intruder is less understood. We found that during
      peak territorial and mating activity, both color morphs and sexes can exhibit
      aggression bias, but whether they do so depends on the strategy (morph) of the
      intruder. During simulated territorial intrusions, resident white-striped males
      and tan-striped females, which represent the opposite ends of a continuum from
      high to low territorial aggression, altered their territorial responses according
      to intruder morph. Tan-striped males and white-striped females, which represent
      the middle of the continuum, did not show a bias. We propose that because of the
      disassortative mating system and morph differences in reproductive strategy, the
      fitness risks of intrusions vary according to the morphs of the resident and the
      intruder, and that aggression bias is an attuned response to varying threats to
      fitness.

PMID- 23119093
TI  - An fMRI study exploring the overlap and differences between neural
      representations of physical and recalled pain.
AB  - Implementing a recall paradigm without hypnosis, we use functional MRI (fMRI) to
      explore and compare nociceptive and centrally-driven pain experiences. We posit
      that a trace of a recent nociceptive event can be used to create sensory-re
      experiencing of pain that can be qualified in terms of intensity and vividness.
      Fifteen healthy volunteers received three levels of thermal stimuli (warm, low
      pain and high pain) and subsequently were asked to recall and then rate this
      experience. Neuroimaging results reveal that recalling a previous sensory
      experience activates an extensive network of classical pain processing structures
      except the contralateral posterior insular cortex. Nociceptive-specific
      activation of this structure and the rated intensity difference between physical
      and recalled pain events allow us to investigate the link between the quality of
      the original nociceptive stimulus and the mental trace, as well as the
      differences between the accompanying neural responses. Additionally, by
      incorporating the behavioural ratings, we explored which brain regions were
      separately responsible for generating either an accurate or vivid recall of the
      physical experience. Together, these observations further our understanding of
      centrally-mediated pain experiences and pain memory as well as the potential
      relevance of these factors in the maintenance of chronic pain.

PMID- 23119094
TI  - Effects of population size on synchronous display of female and male flowers and
      reproductive output in two monoecious Sagittaria species.
AB  - BACKGROUND: Flowering synchrony and floral sex ratio have the potential to
      influence the mating opportunities and reproductive success through female
      function. Here, we examine the variances in synchronous display of female and
      male function, ratio of male to female flowers per day and subsequently
      reproductive output in small populations of two monoecious plants, Sagittaria
      trifolia and Sagittaria graminea. METHODOLOGY/PRINCIPAL FINDING: We created plant
      populations of size 2, 4, 10 and 20 and recorded the daily number of blooming
      male and female flowers per plant to determine daily floral display, flowering
      synchrony index and ratio of male to female flowers per day. We also harvested
      the fruits, counted the seeds and calculated the number of fruits and seeds per
      flower to measure reproductive success through female function. There is less
      overlap in flowering time of female and male function in smaller populations than
      in larger populations. Most importantly, we found that male-biased floral sex
      ratio and imbalanced display period of female and male function for individual
      plant can lead to a population-size-dependent ratio of male to female flowers per
      day. Increasing ratio of male to female flowers per day was generally associated
      with a greater percentage of fruit production. CONCLUSIONS/SIGNIFICANCE: Our
      results highlight the importance of flowering synchrony of female and male
      function and population-size-dependent ratio of male to female flowers per day
      for female reproductive success. This finding improves our understanding of a
      mechanism that reduces reproductive success in small populations.

PMID- 23119096
TI  - Internal habitat quality determines the effects of fragmentation on austral
      forest climbing and epiphytic angiosperms.
AB  - Habitat fragmentation has become one of the major threats to biodiversity
      worldwide, particularly in the case of forests, which have suffered enormous
      losses during the past decades. We analyzed how changes in patch configuration
      and habitat quality derived from the fragmentation of austral temperate
      rainforests affect the distribution of six species of forest-dwelling climbing
      and epiphytic angiosperms. Epiphyte and vine abundance is primarily affected by
      the internal characteristics of patches (such as tree size, the presence of
      logging gaps or the proximity to patch edges) rather than patch and landscape
      features (such as patch size, shape or connectivity). These responses were
      intimately related to species-specific characteristics such as drought- or shade
      tolerance. Our study therefore suggests that plant responses to fragmentation are
      contingent on both the species' ecology and the specific pathways through which
      the study area is being fragmented, (i.e. extensive logging that shaped the
      boundaries of current forest patches plus recent, unregulated logging that
      creates gaps within patches). Management practices in fragmented landscapes
      should therefore consider habitat quality within patches together with other
      spatial attributes at landscape or patch scales.

PMID- 23119091
TI  - MYC gene delivery to adult mouse utricles stimulates proliferation of postmitotic
      supporting cells in vitro.
AB  - The inner ears of adult humans and other mammals possess a limited capacity for
      regenerating sensory hair cells, which can lead to permanent auditory and
      vestibular deficits. During development and regeneration, undifferentiated
      supporting cells within inner ear sensory epithelia can self-renew and give rise
      to new hair cells; however, these otic progenitors become depleted postnatally.
      Therefore, reprogramming differentiated supporting cells into otic progenitors is
      a potential strategy for restoring regenerative potential to the ear. Transient
      expression of the induced pluripotency transcription factors, Oct3/4, Klf4, Sox2,
      and c-Myc reprograms fibroblasts into neural progenitors under neural-promoting
      culture conditions, so as a first step, we explored whether ectopic expression of
      these factors can reverse supporting cell quiescence in whole organ cultures of
      adult mouse utricles. Co-infection of utricles with adenoviral vectors separately
      encoding Oct3/4, Klf4, Sox2, and the degradation-resistant T58A mutant of c-Myc
      (c-MycT58A) triggered significant levels of supporting cell S-phase entry as
      assessed by continuous BrdU labeling. Of the four factors, c-MycT58A alone was
      both necessary and sufficient for the proliferative response. The number of BrdU
      labeled cells plateaued between 5-7 days after infection, and then decreased ~60%
      by 3 weeks, as many cycling cells appeared to enter apoptosis. Switching to
      differentiation-promoting culture medium at 5 days after ectopic expression of c
      MycT58A temporarily attenuated the loss of BrdU-labeled cells and accompanied a
      very modest but significant expansion of the sensory epithelium. A small number
      of the proliferating cells in these cultures labeled for the hair cell marker,
      myosin VIIA, suggesting they had begun differentiating towards a hair cell fate.
      The results indicate that ectopic expression of c-MycT58A in combination with
      methods for promoting cell survival and differentiation may restore regenerative
      potential to supporting cells within the adult mammalian inner ear.

PMID- 23119095
TI  - Deficits in LTP induction by 5-HT2A receptor antagonist in a mouse model for
      fragile X syndrome.
AB  - Fragile X syndrome is a common inherited form of mental retardation caused by the
      lack of fragile X mental retardation protein (FMRP) because of Fmr1 gene
      silencing. Serotonin (5-HT) is significantly increased in the null mutants of
      Drosophila Fmr1, and elevated 5-HT brain levels result in cognitive and
      behavioral deficits in human patients. The serotonin type 2A receptor (5-HT2AR)
      is highly expressed in the cerebral cortex; it acts on pyramidal cells and
      GABAergic interneurons to modulate cortical functions. 5-HT2AR and FMRP both
      regulate synaptic plasticity. Therefore, the lack of FMRP may affect
      serotoninergic activity. In this study, we determined the involvement of FMRP in
      the 5-HT modulation of synaptic potentiation with the use of primary cortical
      neuron culture and brain slice recording. Pharmacological inhibition of 5-HT2AR
      by R-96544 or ketanserin facilitated long-term potentiation (LTP) in the anterior
      cingulate cortex (ACC) of WT mice. The prefrontal LTP induction was dependent on
      the activation of NMDARs and elevation of postsynaptic Ca(2+) concentrations. By
      contrast, inhibition of 5-HT2AR could not restore the induction of LTP in the ACC
      of Fmr1 knock-out mice. Furthermore, 5-HT2AR inhibition induced AMPA receptor
      GluR1 subtype surface insertion in the cultured ACC neurons of Fmr1 WT mice,
      however, GluR1 surface insertion by inhibition of 5-HT2AR was impaired in the
      neurons of Fmr1KO mice. These findings suggested that FMRP was involved in
      serotonin receptor signaling and contributed in GluR1 surface expression induced
      by 5-HT2AR inactivation.

PMID- 23119097
TI  - Reanalysis of RNA-sequencing data reveals several additional fusion genes with
      multiple isoforms.
AB  - RNA-sequencing and tailored bioinformatic methodologies have paved the way for
      identification of expressed fusion genes from the chaotic genomes of solid
      tumors. We have recently successfully exploited RNA-sequencing for the discovery
      of 24 novel fusion genes in breast cancer. Here, we demonstrate the importance of
      continuous optimization of the bioinformatic methodology for this purpose, and
      report the discovery and experimental validation of 13 additional fusion genes
      from the same samples. Integration of copy number profiling with the RNA
      sequencing results revealed that the majority of the gene fusions were promoter
      donating events that occurred at copy number transition points or involved high
      level DNA-amplifications. Sequencing of genomic fusion break points confirmed
      that DNA-level rearrangements underlie selected fusion transcripts. Furthermore,
      a significant portion (>60%) of the fusion genes were alternatively spliced. This
      illustrates the importance of reanalyzing sequencing data as gene definitions
      change and bioinformatic methods improve, and highlights the previously
      unforeseen isoform diversity among fusion transcripts.

PMID- 23119098
TI  - Trait values, not trait plasticity, best explain invasive species' performance in
      a changing environment.
AB  - The question of why some introduced species become invasive and others do not is
      the central puzzle of invasion biology. Two of the principal explanations for
      this phenomenon concern functional traits: invasive species may have higher
      values of competitively advantageous traits than non-invasive species, or they
      may have greater phenotypic plasticity in traits that permits them to survive the
      colonization period and spread to a broad range of environments. Although there
      is a large body of evidence for superiority in particular traits among invasive
      plants, when compared to phylogenetically related non-invasive plants, it is less
      clear if invasive plants are more phenotypically plastic, and whether this
      plasticity confers a fitness advantage. In this study, I used a model group of 10
      closely related Pinus species whose invader or non-invader status has been
      reliably characterized to test the relative contribution of high trait values and
      high trait plasticity to relative growth rate, a performance measure standing in
      as a proxy for fitness. When grown at higher nitrogen supply, invaders had a
      plastic RGR response, increasing their RGR to a much greater extent than non
      invaders. However, invasive species did not exhibit significantly more phenotypic
      plasticity than non-invasive species for any of 17 functional traits, and trait
      plasticity indices were generally weakly correlated with RGR. Conversely,
      invasive species had higher values than non-invaders for 13 of the 17 traits,
      including higher leaf area ratio, photosynthetic capacity, photosynthetic
      nutrient-use efficiency, and nutrient uptake rates, and these traits were also
      strongly correlated with performance. I conclude that, in responding to higher N
      supply, superior trait values coupled with a moderate degree of trait variation
      explain invasive species' superior performance better than plasticity per se.

PMID- 23119099
TI  - Ex vivo evidence for the contribution of hemodynamic shear stress abnormalities
      to the early pathogenesis of calcific bicuspid aortic valve disease.
AB  - The bicuspid aortic valve (BAV) is the most common congenital cardiac anomaly and
      is frequently associated with calcific aortic valve disease (CAVD). The most
      prevalent type-I morphology, which results from left-/right-coronary cusp fusion,
      generates different hemodynamics than a tricuspid aortic valve (TAV). While
      valvular calcification has been linked to genetic and atherogenic
      predispositions, hemodynamic abnormalities are increasingly pointed as potential
      pathogenic contributors. In particular, the wall shear stress (WSS) produced by
      blood flow on the leaflets regulates homeostasis in the TAV. In contrast, WSS
      alterations cause valve dysfunction and disease. While such observations support
      the existence of synergies between valvular hemodynamics and biology, the role
      played by BAV WSS in valvular calcification remains unknown. The objective of
      this study was to isolate the acute effects of native BAV WSS abnormalities on
      CAVD pathogenesis. Porcine aortic valve leaflets were subjected ex vivo to the
      native WSS experienced by TAV and type-I BAV leaflets for 48 hours.
      Immunostaining, immunoblotting and zymography were performed to characterize
      endothelial activation, pro-inflammatory paracrine signaling, extracellular
      matrix remodeling and markers involved in valvular interstitial cell activation
      and osteogenesis. While TAV and non-coronary BAV leaflet WSS essentially
      maintained valvular homeostasis, fused BAV leaflet WSS promoted fibrosa
      endothelial activation, paracrine signaling (2.4-fold and 3.7-fold increase in
      BMP-4 and TGF-beta1, respectively, relative to fresh controls), catabolic enzyme
      secretion (6.3-fold, 16.8-fold, 11.7-fold, 16.7-fold and 5.5-fold increase in MMP
      2, MMP-9, cathepsin L, cathepsin S and TIMP-2, respectively) and activity (1.7
      fold and 2.4-fold increase in MMP-2 and MMP-9 activity, respectively), and bone
      matrix synthesis (5-fold increase in osteocalcin). In contrast, BAV WSS did not
      significantly affect alpha-SMA and Runx2 expressions and TIMP/MMP ratio. This
      study demonstrates the key role played by BAV hemodynamic abnormalities in CAVD
      pathogenesis and suggests the dependence of BAV vulnerability to calcification on
      the local degree of WSS abnormality.

PMID- 23119101
TI  - Implicit learning of arithmetic regularities is facilitated by proximal contrast.
AB  - Natural number arithmetic is a simple, powerful and important symbolic system.
      Despite intense focus on learning in cognitive development and educational
      research many adults have weak knowledge of the system. In current study
      participants learn arithmetic principles via an implicit learning paradigm.
      Participants learn not by solving arithmetic equations, but through viewing and
      evaluating example equations, similar to the implicit learning of artificial
      grammars. We expand this to the symbolic arithmetic system. Specifically we find
      that exposure to principle-inconsistent examples facilitates the acquisition of
      arithmetic principle knowledge if the equations are presented to the learning in
      a temporally proximate fashion. The results expand on research of the implicit
      learning of regularities and suggest that contrasting cases, show to facilitate
      explicit arithmetic learning, is also relevant to implicit learning of
      arithmetic.

PMID- 23119100
TI  - Slit2N/Robo1 inhibit HIV-gp120-induced migration and podosome formation in
      immature dendritic cells by sequestering LSP1 and WASp.
AB  - Cell-mediated transmission and dissemination of sexually-acquired human
      immunodeficiency virus 1 (HIV-1) in the host involves the migration of immature
      dendritic cells (iDCs). iDCs migrate in response to the HIV-1 envelope protein,
      gp120, and inhibiting such migration may limit the mucosal transmission of HIV-1.
      In this study, we elucidated the mechanism of HIV-1-gp120-induced
      transendothelial migration of iDCs. We found that gp120 enhanced the binding of
      Wiskott-Aldrich Syndrome protein (WASp) and the Actin-Related Protein 2/3
      (Arp2/3) complex with beta-actin, an interaction essential for the proper
      formation of podosomes, specialized adhesion structures required for the
      migration of iDCs through different tissues. We further identified Leukocyte
      Specific Protein 1 (LSP1) as a novel component of the WASp-Arp2/3-beta-actin
      complex. Pretreating iDCs with an active fragment of the secretory glycoprotein
      Slit2 (Slit2N) inhibited HIV-1-gp120-mediated migration and podosome formation,
      by inducing the cognate receptor Roundabout 1 (Robo1) to bind to and sequester
      WASp and LSP1 from beta-actin. Slit2N treatment also inhibited Src signaling and
      the activation of several downstream molecules, including Rac1, Pyk2, paxillin,
      and CDC42, a major regulator of podosome formation. Taken together, our results
      support a novel mechanism by which Slit2/Robo1 may inhibit the HIV-1-gp120
      induced migration of iDCs, thereby restricting dissemination of HIV-1 from
      mucosal surfaces in the host.

PMID- 23119102
TI  - Gastrointestinal manifestations of neurofibromatosis type 1 (Recklinghausen's
      disease): clinicopathological spectrum with pathogenetic considerations.
AB  - Neurofibromatosis type 1 (NF-1, Recklinghausen disease) is the most common
      hereditary multitumor syndrome with an incidence at birth of approximately
      1:3000. However, the significant variation in the expression of the disease not
      infrequently precludes early diagnosis. As a consequence of non-familiarity with
      their frequency and wide clinicopathological spectrum, gastrointestinal
      manifestations of NF-1 are seldom thought of in routine clinical practice and
      might thus be significantly under-recognized. Their heterogeneous spectrum ranges
      from localized microscopic proliferative lesions of autonomic nerves and
      interstitial cells of Cajal and diffuse microscopic ganglio/neuro/fibromatosis to
      grossly recognizable mass-forming neurofibromas and gastrointestinal stromal
      tumors (GIST). Furthermore, neuroendocrine neoplasms, particularly of the
      periampullary duodenum seem to be quite characteristic of this disease. Based on
      our own experience and the available literature, this review summarizes and
      discusses the clinicopathological spectrum of gastrointestinal manifestations of
      NF-1 including putative proliferative precursor lesions with emphasis on the
      differential diagnostic aspects of these disorders and their molecular
      pathogenesis. In addition, this review underlines the great value of specific
      gastrointestinal findings in uncovering undiagnosed or missed NF-1 cases.

PMID- 23119104
TI  - GP73 expression and its significance in the diagnosis of hepatocellular
      carcinoma: a review.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, and
      its incidence has been increasing worldwide. Serum alpha-fetoprotein (AFP) levels
      and abdominal ultrasound have been widely used for diagnosis as well as
      surveillance of HCC. However, the sensitivity and specificity of both AFP levels
      and ultrasound for HCC surveillance have some shortcomings, particularly in the
      early stages of the disease. Golgi protein-73 (GP73) is a type II Golgi-localized
      integral membrane protein that is normally expressed in epithelial cells of many
      human tissues. It is essential for human survival, and might have multiple roles
      for GP73 in epithelial cell function such as in the kidney and liver. However,
      details of its biochemical function and regulation of GP73 expression are unknown
      at present. GP73 expression is upregulated in serum samples from patients with
      liver disease, with expression being highest in HCC. Therefore, it may be useful
      as a new serum marker for detection of HCC in at high-risk population. But, this
      hypothesis needs to be proven in large cohorts.

PMID- 23119105
TI  - Accuracy of grading of urothelial carcinoma on urine cytology: an analysis of
      interobserver and intraobserver agreement.
AB  - BACKGROUND: Urine samples of known urothelial carcinoma were independently graded
      by 3 pathologists with (MS, MR) and without (AO) fellowship training in
      cytopathology using a modified version of the 2004 2-tiered World Health
      Organization classification system. By measuring interobserver and intraobserver
      agreement among pathologists, compared with the gold standard of
      biopsy/resection, specimen accuracy and reproducibility of grading in urine was
      determined. METHODS: 44 urine cytology samples were graded as low or high-grade
      by 3 pathologists with a 2-3 week interval between grading. Pathologists were
      blinded to their and others' grades and histologic diagnoses. Coefficient kappa
      was used to measure interobserver and intraobserver agreement among pathologists.
      Accuracy was measured by percentage agreement with the biopsy/resection
      separately for each pathologist, and for all pathologists and occasions combined.
      RESULTS: The overall accuracy was 77% (95% C.I., 72%-82%). Pathologist AO was
      significantly more accurate than MR on occasion 1 (p = 0.006) and 2 (p = 0.039).
      No other significant differences were found among the observers. Interobserver
      agreement using coefficient kappa was unacceptably low, with all but one of the
      kappa value being less than 0.40, the cutoff for a "fair" degree of agreement.
      Intraobserver agreement, as measured by coefficient kappa, was adequate.
      CONCLUSIONS: Our study underscores the lack of precision and subjective nature of
      grading urothelial carcinoma on urine samples. There was poor inter- and
      intraobserver agreement among pathologists despite fellowship training in
      cytopathology. Clinicians and cytopathologists should be mindful of this pitfall
      and avoid grading urothelial carcinoma on urine samples, especially since grading
      may impact patient management.

PMID- 23119103
TI  - Hematopoietic stem cell derived carcinoma-associated fibroblasts: a novel origin.
AB  - Researchers have begun to appreciate the significant role that the
      microenvironment plays in tumorigenesis and are now shedding light on the role of
      the stroma in induction and progression of solid tumors. While the stroma of
      solid tumors is comprised of many cell types, including vascular and immune
      cells, one of the most prominent cell types in the tumor stroma is the
      fibroblast, called the carcinoma-associated fibroblast (CAF) or tumor-associated
      fibroblast (TAF). The interaction between CAFs and tumor cells is quite complex.
      CAFs have been implicated in tumor angiogenesis, immunosuppression, tumor cell
      proliferation and aggressiveness, genetic instability, and metastasis. However,
      their specific roles in each of these processes have only been partially
      elucidated. Determining the role of CAFs has been complicated by the fact that
      researchers have demonstrated heterogeneity in the stromal fibroblast population.
      This heterogeneity has brought about the concept of multiple origins for CAFs.
      While many origins of CAFs have been suggested, in our own laboratory we have
      identified a novel hematopoietic stem cell (HSC) origin of CAFs. Given the
      profound role of CAFs in tumor progression and prognosis, the CAF represents an
      exciting potential therapeutic target. The heterogeneity of the CAF population
      makes research directed at investigating the roles and origins of CAFs critical
      to development of such anti-tumor therapies.

PMID- 23119106
TI  - Optimization of prostate cancer diagnosis by increasing the number of core
      biopsies based on gland volume.
AB  - In this prospective, non-randomized phase-I clinical trial, we comparatively
      studied the performance of six laterally-directed biopsies or the modified fan
      shaped biopsies (MFSB), midline sextant biopsies (MB), and transition zone
      biopsies (TZB) and examine their prostate cancer (PCa) detection rates. A total
      of 114 patients received combinations of MFSB, MB, and TZB based on prostate
      gland volume: those <=15 cc received 8 biopsies; those >15 cc but <= 50 cc
      received 14 biopsies; and those >50 cc received 20 biopsies. The mean prostate
      specific antigen (PSA) level, Gleason score, and prostate volume were 8.0 ng/ml,
      6.4, and 47 cc, respectively. PCa detection rate of the MB was 25% while the MFSB
      was 22%. The overall PCa detection rate was 33.3% with all biopsies. PCa and high
      grade prostatic intraepithelial neoplasia (HG-PIN) detection rates decrease as
      the size of the prostate increases. PCa detection rates were 50.0% for volumes
      <=19.9 cc and volumes of >50 cc had a detection rate of 25.8%. PSA levels of <3.0
      had PCa detection rates of 15% which increased to 58% with PSA levels >9.0. In a
      multivariate analysis, only TZB was significant for PCa diagnosed by PSA
      (beta=7.4, p<0.01). Our study showed that it is important to perform both the
      lateral MFSB and the MB to improve overall PCa detections rates. Thus, we
      recommend performing MB, MFSB, and TZB based on prostate volume, as follows: 8
      biopsies for <=15 cc; 14 for those >15 cc but <=50 cc, and 14-20 for those >50
      cc.

PMID- 23119109
TI  - Endometrioid adenocarcinoma of the ovary arising in atypical endometriosis.
AB  - Ovarian endometriosis can transform into malignant tumors, and ovarian carcinomas
      relatively frequently contain foci of endometriosis. In this study, the author
      reviewed 15 cases of endometrioid adenocarcinoma of the ovary in the last 15
      years of our pathology laboratory in search for the presence of endometriosis
      within the tumor. Six (40%) of the 15 endometrioid adenocarcinoma were found to
      have endometriosis in the tumor. All of the endometriosis were atypical. The age
      of the 6 patients ranged from 44 year to 78 year with a median of 59 years.
      Grossly, the endometrial adenocarcinomas with endometriosis were characterized by
      unilocular cystic tumors in 5 cases and multilocular cystic tumor in one case.
      Histologically, the grade of endometrioid carcinoma was grade I in 3 cases, grade
      II in 2 cases and grade III in 1 case. Endometriosis was mixed with the tumors or
      was present adjacent to the tumor. The endometriosis was composed of a layer of
      atypical epithelium (atypical endometriosis), and gradual merges between
      endometriosis and carcinoma were present in 3 cases. These findings suggest that
      atypical endometriosis can transform into endometrioid carcinoma.

PMID- 23119108
TI  - Effect of recombinant adenovirus coding for endomorphin-2 on neuropathic pain in
      rats.
AB  - OBJECTIVE: To construct a transgene expressing human endomorphin-2 by linking the
      signal peptide of mouse nerve growth factor (PN) to a human endomorphin-2 DNA
      sequence containing a short linker recognized by the protease FURIN and test the
      analgesic effect of endomorphin-2 on neuropathic pain. METHODS: The transgene was
      inserted into the cosmid pAxCAwt to generate PN-EM-2-pAxCAwt. The recombinant
      adenovirus Ad-PNEM2 was packaged and propagated in HEK293 cells. After the Ad
      PNEM2-infected NIH3T3 cells had been cultured, protein expression was examined by
      immunofluorescence and ELISA. A CCI rat model was constructed and the Ad-PNEM2
      was administered intrathecally. The rats' pain thresholds (PWL) were measured and
      the presence of endomorphin-2 in the cerebrospinal fluid was confirmed through
      ELISA. RESULTS: The Ad-PNEM2 expressed endomorphin-2 smoothly and abundantly in
      NIH3T3 cells at a significantly higher rate than the viral control (P<0.01) or
      blank control (P<0.01). The expressed endomorphin-2 was mainly observed in the
      cytoplasm. The concentration of endomorphin-2 in the cerebrospinal fluid
      increased 1 day after injection and peaked between 7 and 14 days after injection.
      After injection, PWL approached normal levels in the operated study group. No
      significant change was observed in the control groups. There was a significant
      correlation between PWL and endomorphin-2 level (r = 0.944, P<0.001). CONCLUSION:
      The constructed human endomorphin-2 transgene was expressed effectively, and
      endomorphin-2 expressed by the recombinant adenovirus altered the threshold to
      thermal stimulus and showed good analgesic effect.

PMID- 23119107
TI  - The protection of acetylcholinesterase inhibitor on beta-amyloid-induced the
      injury of neurite outgrowth via regulating axon guidance related genes expression
      in neuronal cells.
AB  - Cognitive deficits in AD correlate with progressive synaptic dysfunction and
      loss. The Rho family of small GTPases, including Rho, Rac, and Cdc42, has a
      central role in cellular motility and cytokinesis. Acetylcholinesterase inhibitor
      has been found to protect cells against a broad range of reagents-induced
      injuries. Present studies examined if the effect of HupA on neurite outgrowth in
      Abeta-treated neuronal cells executed via regulating Rho-GTPase mediated axon
      guidance relative gene expression. Affymetrix cDNA microarray assay followed by
      real-time RT-PCR and Western Blotting analysis were used to elucidate and analyze
      the signaling pathway involved in Abeta and HupA's effects. The effects of Abeta
      and HupA on the neurite outgrowth were further confirmed via immunofluorescence
      staining. Abeta up-regulated the mRNA expressions of NFAT5, LIMK1, EPHA1, NTN4
      and RAC2 markedly in SH-SY5Y cells. Co-incubation of Abeta and HupA reversed or
      decreased the changes of NFAT5, NTN4, RAC2, CDC42 and SEMA4F. HupA treated alone
      increased NFAT5, LIMK1, NTN4 significantly. Following qRT-PCR validation showed
      that the correlation of the gene expression ratio between microarray and qRT-PCR
      is significant. Western blot result showed that the change of CDC42 protein is
      consistent with the mRNA level while RAC2 is not. The morphological results
      confirmed that HupA improved, or partly reversed, the Abeta-induced damage of
      neurite outgrowth. The protective effect of HupA from Abeta induced morphological
      injury might be correlative to, at least partially, regulating the network of
      neurite outgrowth related genes.

PMID- 23119110
TI  - Primary and metastatic cardiac sarcomas: a 12-year experience at a German heart
      center.
AB  - BACKGROUND: Primary and metastatic cardiac sarcomas represent a heterogeneous
      group of rare neoplasms with varying clinical course and diverse histogenetic
      line of differentiation. To date, there exist no uniform guidelines for their
      surgical and/or oncological treatment. METHODS: We evaluated retrospectively all
      patients undergoing cardiac surgery for primary or secondary cardiac sarcoma in
      the period 1999-2011 at the Erlangen Heart Centre to analyze their
      clinicopathological spectrum, treatment and outcome. RESULTS: Five patients (3
      women & 2 men; mean age: 46 years; range: 28-81 years) had primary cardiac
      sarcomas (6.7% of primary cardiac tumors) and 4 had cardiac metastasis from soft
      tissue sarcoma (1 case each of osteosarcoma, myxoid liposarcoma, alveolar soft
      part sarcoma and pleomorphic spindle cell sarcoma). Primary sarcomas were located
      in the left atrium (n=3), left ventricle (n=1) and right atrium (n=1).
      Histological types were myxosarcoma (3), pleomorphic undifferentiated sarcoma (1)
      and angiosarcoma (1). Four patients died at 2-64 months (mean, 24.5 months).
      Sarcoma metastasis to the heart developed at a mean of 109.5 months from initial
      diagnosis (range, 5-240 months). Three of them died of disease at a mean of 14
      months after cardiac surgery and one is disease free 34 months after heart
      transplantation for metastasis. CONCLUSIONS: Primary and metastatic cardiac
      sarcomas are very heterogeneous in their histological appearance, clinical
      presentation and course of the disease. Radical surgery combined with
      chemoradiation is promising in patients with resectable disease and may
      significantly prolong survival. Cardiac transplantation represents an emerging
      strategy for patients with isolated unresectable cardiac involvement.

PMID- 23119111
TI  - Tumor cell nuclear diameter and CD30 expression as potential prognostic parameter
      in patients with extranodal NK/T-cell lymphoma, nasal type.
AB  - Extranodal natural killer/T-cell lymphoma, nasal type (nasal ENKTL) is a distinct
      clinicopathologic entity of lymphoid tumors with variable size and
      differentiation of tumor cells. Nasal ENKTL is related to infection of the tumor
      cells with Epstein-Barr virus (EBV) and virtually all cases contain monoclonal
      episomal EBV DNA and detectable EBV encoded small nuclear RNAs (EBERs). Several
      clinical factors are known for their relation to the prognosis, but
      histopathologic prognostic factors of nasal ENKTL have not yet been well
      established. We evaluated the prognostic value of the longest nuclear diameter of
      EBER+ tumor cells (NDTC) along with the result of CD30 expression. Twenty two
      patients with newly diagnosed nasal ENKTL were evaluated regarding
      clinicopathologic characteristics. NDTC was measured using a computerized image
      analysis system. The results were expressed as the mean diameter of >= 50 cells
      in a patient. Median of the mean NDTC of the patients was 7.32 MUm (5.15-11.27).
      Patients with larger mean NDTC (>= 7.35 MUm) had a poorer event-free survival
      (EFS) than those with smaller mean NDTC (<7.35 MUm; p = 0.024) and had a tendency
      of inferior overall survival (OS) (p = 0.08). Patients with CD30 expression had a
      inferior EFS (p = 0.018) and OS (p = 0.011) compared those without CD30
      expression. The NDTC of EBV infected tumor cell and CD30 expression had relation
      to survival in the current exploratory analysis.

PMID- 23119112
TI  - Down-regulation of GAP-43 by inhibition of caspases-3 in a rat model of
      neuropathic pain.
AB  - BACKGROUND: Neuropathic pain remains a prevalent and persistent clinical problem
      due to incomplete understanding of its pathogenesis. OBJECTIVE: The present study
      aimed to investigate the role of caspase-3 in the neuropathic pain in rats with
      chronic constriction injury (CCI). METHODS: SD rats were randomly assigned four
      groups (n=18 per group): sham group, normal saline group (NS group), Z-DEVD-FMK
      group (DEVD group) and RNA interference group (siRNA group). Z-DEVD-FMK (1 U/30
      MUl), siRNA targeting caspase-3 (10 MUg/30 MUl) and NS of equal volume were
      intrathecally administered once daily for 5 days starting 1 day before surgery in
      the DEVD, siRNA and NS group, respectively. Thermal hyperalgesia was assessed at
      one day before and 1, 2, 4, 5, 6, 7 and 10 days after surgery. The mRNA and
      protein expressions of caspase-3 were measured by real time PCR and
      immunofluorescence assay. Apoptosis was detected by TUNEL staining. GAP-43
      expression was measured by immunofluorescence and western blot assays. RESULTS:
      The right paw withdrawal latency (PWL) was decreased after CCI (P<0.05). TUNEL
      positive neurons and the mRNA and protein expressions of caspase-3 in the spinal
      cord were increased significantly. After Z-DEVD-FMK or siRNA treatment, TUNEL
      positive neurons were decreased, PWLs increased (P<0.05) and the mRNA and protein
      expressions of caspase-3 decreased. The expression of GAP-43, a sprouting related
      protein, was decreased in the DEVD and siRNA group as compared to NS group
      (P<0.05). Up-regulation of GAP-43 following CCI was decreased following caspase-3
      inhibition. Following sciatic nerve ligation, the gene expression, translation
      and transcription are significantly changed in the neurons which finally results
      in neuron apoptosis. The neuron apoptosis induce the up-regulation of GAP-43
      expression leading to hyperalgesia. CONCLUSION: Caspase-3 mediated neuron
      apoptosis is probably responsible for the neuropathic pain in CCI rats.
      Inhibition of caspase-3 may serve as a treatment of neuropathic pain.

PMID- 23119113
TI  - Normalized autofluorescence imaging diagnostics in upper GI tract: a new method
      to improve specificity in neoplasia detection.
AB  - BACKGROUND & AIMS: This study was performed to improve the autofluorescence
      imaging (AFI) in the upper GI tract by applying a new method of normalized
      autofluorescence (NAFI) obtained via tri-modal imaging. OBJECTIVE: NAFI may
      provide lower false positive rate to achieve ultimately better specificity at
      acceptable sensitivity. PATIENTS AND METHODS: This is a prospective, controlled
      single-centre study. 18 patients with suspected esophagus or stomach cancer
      undergoing esophagogastroduodenoscopy (EGD) were enrolled between February and
      May 2010. After endoscopy each patient was assigned into one of two groups: (1)
      non-cancer, including inflammation; (2) cancer group. EGDs were performed using
      video white light endoscopy, followed by AFI/NAFI. The targeted biopsy samples
      were taken from the abnormal areas as well as from adjacent mucosa. NAFI was
      compared versus AFI for cancer diagnostics in terms of specificity and
      sensitivity. RESULTS: NAFI detected all neoplastic lesions. WLE or NBI detected
      no additional neoplasia. The AFI displayed mucosal inflammation and carcinomas of
      esophagus and stomach as dark red color, the normal mucosa background was
      displayed as light green. The NAFI didn't differentiate inflamed tissue from
      normal in majority of cases, but in tumorous mucosa, the cancer areas were
      detected precisely. AFI shows 100% sensitivity but 50% specificity which
      correlates with previous literature data. On the other hand, NAFI demonstrated
      lower sensitivity (88%) but higher specificity compared to AFI (69%).
      CONCLUSIONS: Measuring the NAFI instead of the AFI was found improving the
      specificity of cancer diagnosis. Use of fiber-optic endoscopes to analyze AFI and
      possible endoscopic and histological sampling error are the main potential
      limitations of this method.

PMID- 23119114
TI  - Clinicopathological significance of PTEN and bcl2 expressions in oral squamous
      cell carcinoma.
AB  - A high frequency of mutations at the PTEN locus has been noticed in carcinoma of
      oral. However, the role of PTEN alternations and its association with outcome
      variables in the genesis of oral carcinoma is not understood fully. The purpose
      of our study was to examine the impact of PTEN and Bcl2 in the genesis of
      squamous cell carcinoma of oral. Total numbers of 60 histopathologically
      confirmed cases of squamous cell carcinoma and 15 cases of inflammatory lesion of
      oral specimens were studied. We assessed PTEN and bcl2 overexpression by the use
      of anti-PTEN and anti-bcl2 antibody through immunohistochemistry as directed by
      the manufacturer. There was progressive loss of PTEN expression from inflammatory
      lesion to OSCC (p<0.05). Significant differences were found for PTEN expression
      between inflammatory lesion and OSCC. The difference in expression pattern of
      PTEN in gender did not reach statistical significance (p>0.05). The expression of
      bcl2 was found to be restricted to tumor cells in well and moderately
      differentiated tumors. The intense expression of bcl2 was observed throughout the
      tumor cell in poorly differentiated tumors. The overexpression of bcl2 and loss
      of PTEN expression were correlated to poor differentiation, lymph node
      involvement and late stages. Thus, alteration of PTEN and bcl2 is likely an
      important molecular event in pathogenesis and carcinogenesis of oral carcinoma.

PMID- 23119115
TI  - Leptomeningeal carcinomatosis as initial presentation in adenocarcinoma of lung
      with signet ring cell features: an autopsy case report.
AB  - Signet ring cell (SRC) features are rare but well-recognized cytological changes
      of pulmonary adenocarcinoma (PA). PA with SRC features (PA-SRC) is frequently
      associated with anaplastic lymphoma kinase (ALK) gene rearrangement, and
      recognition of PA-SRC may be important for the administration of targeted
      treatment. To the authors' knowledge, leptomeningeal carcinomatosis (LMC) as an
      initial presentation of PA-SRC has not yet been reported. We report an autopsy
      case from a 59-year-old female who presented with intractable headache for 6
      weeks and died of LMC as a result of metastatic PA-SRC. Premortem brain MRI
      showed nonspecific leptomeningeal enhancement. At autopsy, a tan rubbery mass was
      found in the hilar area of the right lung, which also surrounded the lower
      trachea and carotid arteries. A right posteromedial middle lobe mass was also
      found. Leptomeninges were slightly thickened, without discrete masses.
      Microscopic examination of the lung mass and leptomeninges showed solid sheets
      and nests of malignant cells with pleomorphic nuclei and frequent SRC features
      which comprised 50% of the mass. Immunohistochemically, the tumor cells
      demonstrated strong diffuse expression of cytokeratin (CK)-7, TTF-1, and napsin
      A. Immunostains for CK-20 and ALK were negative. These features were consistent
      with PA-SRC. It has been reported that approximately 70% of PAs demonstrate ALK
      gene rearrangement when SRCs comprised >10% of the tumor cells. The presence of
      SRCs can be indicative of a lung primary and, because of frequent ALK gene
      rearrangement in PA-SRC, proper recognition of PA-SRC may be important in
      determining whether further testing is advisable (e.g., ALK immunostaining and/or
      ALK gene rearrangement).

PMID- 23119116
TI  - Ectopic immature renal tissue: clues for diagnosis and management.
AB  - Ectopic immature renal tissue has rarely been reported in literature, associated
      or not with teratoma. Its finding could be matter of concern, owing to the
      occasional possibility that Wilms tumor may develop in this setting. We report a
      1-year-old male patient who underwent surgery for a sacral subcutaneous small
      teratoma with a prevalent component of immature renal tissue. The lesion appeared
      completely excised and, in absence of features of malignancy, only follow-up was
      suggested. The patient was alive and well 15 months postoperatively. Whenever
      ectopic immature renal tissue is detected, a proper histological interpretation
      is mandatory, in order to plan a suitable treatment of the patient. From an
      extensive analysis of cases reported in literature we draw some practical
      suggestions for the diagnosis and treatment of this rare condition.

PMID- 23119117
TI  - The histogenic origin of melanoma arising in respiratory epithelium of a
      teratomatous germ cell tumor of the mediastinum: an enigma unraveled from an
      unlikely source.
AB  - Mixed germ cell tumors are rare neoplasms that are known to occur in the anterior
      mediastinum. Characterized by two or more types of germ cell components, these
      tumors comprise upwards of 25% of mediastinal germ cell tumors. Even rarer are
      those harboring somatic-type malignancies such as carcinoma, sarcoma, and
      hematopoietic malignancies. To date, however, there are no known cases of
      melanoma arising in a malignant mixed germ cell tumor of the anterior
      mediastinum. We describe the first case of malignant melanoma with spindle and
      epithelioid components arising from respiratory epithelium in a mediastinal
      malignant mixed germ cell tumor of a 32-year-old male. In addition, we also
      provide evidence supporting the theory of neuroendocrine cells as the origin of
      melanoma arising in the respiratory epithelium. This case emphasizes the need to
      carefully evaluate all germ cell tumors, not only for a myriad of benign
      embryological components, but also for malignancies arising in these components,
      as they might change the prognosis and patient's course of treatment. This
      microscopic approach should bring to light the diversity of mixed germ cell
      tumors in addition to somatic malignancies with corresponding biologic
      potentials.

PMID- 23119118
TI  - The rare mediastinal lipoma: a postmortem case report.
AB  - Mediastinal lipomas are extremely rare, so there are few reported cases. We
      report a postmortem case of this rare intrathoracic lipoma in a 79-year old
      female cadaver. The gross features of the tumor and histopathological findings
      confirmed the diagnosis of a massive simple benign lipoma. To our knowledge, this
      is the first case to be reported at such an advanced age and the second
      postmortem case found during comprehensive review of literature.

PMID- 23119119
TI  - Giant left atrial myxoma causing drop attacks by prolapsing into the mitral
      valve.
AB  - Atrial myxoma is the most common primary cardiac tumor. Its clinical presentation
      varies greatly from asymptomatic incidental mass to serious life-threatening
      cardiovascular complications. We herein describe the clinicopathological and
      imaging features of a huge left atrial myxoma protruding into the left ventricle
      during diastole and obstructing diastolic filling of the left ventricle thus
      causing drop attacks by prolapsing into the mitral valve. The patient (a 56-year
      old female) underwent emergency surgery with complete removal of a 74 g weighing
      myxoma from the left atrium. She recovered without any complications. Awareness
      of this uncommon acute presentation of atrial myxoma is necessary for timely
      diagnosis and prompt surgical intervention to avoid irreversible cardiovascular
      complications.

PMID- 23119120
TI  - Oncocytic lipoadenoma of the parotid gland: a report of a new case and review of
      the literature.
AB  - Oncocytic lipoadenoma is a rare salivary gland tumour composed of adipose tissue
      and oncocytic epithelial cells in varied proportions. This tumour is still not
      included in the current WHO classification of salivary gland neoplasms. We herein
      report a further case of oncocytic lipoadenoma originating in the parotid gland
      of a 55-year-old woman. The tumour presented as a slowly growing asymptomatic
      left-sided parotid gland mass. The resected tumour measured 2.7 cm in maximum
      diameter and was composed of oncocytoma-like epithelial component admixed with
      mature adipocytes that made up 10% of the whole mass. Foci of sebaceous
      differentiation were seen. This rare variant of lipomatous salivary gland tumours
      is in need of more recognition and should be distinguished from other fat
      containing salivary gland lesions, particularly lipomatous pleomorphic adenoma
      and myoepithelioma.

PMID- 23119121
TI  - Metastatic Merkel cell carcinoma in the bone marrow of a patient with plasma cell
      myeloma and therapy-related myelodysplastic syndrome.
AB  - Merkel cell carcinoma is an aggressive neoplasm of the skin that shows frequent
      lymph node metastases, but has only rarely been reported in the bone marrow.
      Herein we report a case of a 64-year-old male with a history of plasma cell
      myeloma and recent skin diagnosis of Merkel cell carcinoma who presented for a
      routine follow-up bone marrow to assess his myeloma. The biopsy showed persistent
      plasma cell myeloma, trilineage dysplasia, and clusters of neuroendocrine cells
      consistent with metastatic Merkel cell carcinoma. Discussion of this case, a
      review of metastatic Merkel cell carcinoma, and identification of clinical
      settings in which staging bone marrow biopsy may be warranted are presented.

PMID- 23119122
TI  - The critical role of redox homeostasis in shikonin-induced HL-60 cell
      differentiation via unique modulation of the Nrf2/ARE pathway.
AB  - Among various cancer cell lines, the leukemia cell line HL-60 was most sensitive
      to Shikonin, with evidence showing both the prooxidative activities and
      proapoptotic effects of micromolar concentrations of Shikonin. However, the
      mechanism involved in the cytotoxicity of Shikonin in the submicromolar range has
      not been fully characterized. Using biochemical and free radical biological
      experiments in vitro, we identified the prodifferentiated profiles of Shikonin
      and evaluated the redox homeostasis during HL-60 differentiation. The data showed
      a strong dose-response relationship between Shikonin exposure and the
      characteristics of HL-60 differentiation in terms of morphology changes,
      nitroblue tetrazolium (NBT) reductive activity, and the expression level of
      surface antigens CD11b/CD14. During drug exposure, intercellular redox
      homeostasis changes towards oxidation are necessary to support Shikonin-induced
      differentiation, which was proven by additional enzymatic and non-enzymatic redox
      modulators. A statistically significant and dose-dependent increase (P < 0.05)
      was recorded with regard to the unique expression levels of the Nrf2/ARE
      downstream target genes in HL-60 cells undergoing late differentiation, which
      were restored with further antioxidants employed with the Shikonin treatment. Our
      research demonstrated that Shikonin is a differentiation-inducing agent, and its
      mechanisms involve the Nrf2/ARE pathway to modulate the intercellular redox
      homeostasis, thus facilitating differentiation.

PMID- 23119123
TI  - The Synthesis and Antimicrobial Activity of Heterocyclic Derivatives of Totarol.
AB  - The synthesis and antimicrobial activity heterocyclic analogs of the diterpenoid
      totarol are described. An advanced synthetic intermediate with a ketone on the A
      ring is used to attach fused heterocycles and a carbon-to-nitrogen atom
      replacement is made on the B-ring by de novo synthesis. A-ring analogs with an
      indole attached exhibit, for the first time, enhanced antimicrobial activity
      relative to the parent natural product. Preliminary experiments demonstrate that
      the indole analogs do not target the bacterial cell division protein FtsZ as had
      been hypothesized for totarol.

PMID- 23119124
TI  - The oral microflora in obesity and type-2 diabetes.
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) is prevalent in people with obesity.
      It has been proposed that these conditions are related to specific features of
      the microflora of the mouth and lower gastrointestinal (GI) tract. Hyperglycemia
      often resolves quickly after Roux-en-Y gastric bypass (RYGB) but the role of the
      GI microflora cannot be examined easily because of reduced intestinal mobility.
      We propose that the study of microorganisms present in the mouth of patients
      undergoing RYGB will contribute to our understanding of the role of bacteria in
      the pathogenesis of T2DM. OBJECTIVE: To conduct a feasibility study to examine
      differences in oral microbes in obese patients with and without T2DM and to
      determine whether it is feasible to measure changes after gastric bypass surgery.
      METHODS: Individuals with morbid obesity (n=29), of whom 13 had T2DM, were
      studied. Oral rinses, stool samples, and blood samples were obtained before RYGB,
      and oral rinses and blood samples were obtained at 2 and 12 weeks postsurgery.
      RESULTS: Prior to surgery, participants with T2DM had slightly higher total
      levels of oral bacteria than those without diabetes. Those with HbA1c > 6.5% had
      rather lower levels of Bifidobacteria in the mouth and stool. At 2 weeks post
      RYGB, patients with T2DM were able to reduce or discontinue their hypoglycemic
      medications. Stool samples could not be obtained but oral rinses were readily
      available. The levels of oral Bifidobacteria had increased tenfold and levels of
      circulating endotoxin and tumor necrosis factor-alpha had decreased. CONCLUSIONS:
      The study of oral bacteria before and after RYGB is feasible and should be tested
      in larger patient populations to increase our understanding of the role of
      microorganisms in the pathogenesis of obesity and T2DM.

PMID- 23119125
TI  - Associated risk factors and management of chronic diabetic foot ulcers exceeding
      6 months' duration.
AB  - BACKGROUND: The management of chronic diabetic foot ulcers (DFU) poses a great
      challenge to the treating physician and surgeon. The aim of this study was to
      identify the risk factors, clinical presentation, and outcomes associated with
      chronic DFU>6 months' duration. METHODS: This prospective study was performed in
      Jabir Abu Eliz Diabetic Centre (JADC), Khartoum, Sudan. A total of 108 patients
      who had DFU for >6 months were included. Recorded data included patient's
      demographics, DFU presentation, associated comorbidities, and outcomes. DFU
      description included size, depth, protective sensation, perfusion, and presence
      of infection. Comorbidities assessed included eye impairment, renal and heart
      disease. All patients received necessary local wound care with sharp debridement
      of any concomitant necrotic and infected tissues and off-loading with appropriate
      shoe gear and therapeutic devices. RESULTS: The mean age of the studied patients
      was 56+SD 9 years with a male to female ratio of 3:3.3. The mean duration of DFU
      was 18+/-SD 17 months (ranging from 6 to 84 months). Ulcer healing was
      significantly associated with off-loading, mainly the use of total contact cast
      (TCC) (p=0.013). Non-healing ulcerations were significantly associated with
      longer duration of the chronic DFU>12 months (p=0.002), smoking (p=0.000), poor
      glycemic control as evidenced by an elevated HbA1c (>7%), large size (mean SD 8+4
      cm), increased depth (p<0.001), presence of skin callus (p<0.000), impaired limb
      perfusion (p=0.001), impaired protective sensation as measured by 10 g
      monofilament (p=0.002), neuroischemia (p=0.002), and Charcot neuroarthropathy
      (p=0.017). DISCUSSION: Risk factors associated with chronic DFU of>6 months'
      duration included the presentation of an ulcer with increased size and depth,
      with associated skin callus and neuroischemia, in a diabetic patient with a
      history of smoking and increased HbA1c >7%. Off-loading mainly with the use of
      TCC is an effective method of managing long-standing DFU.

PMID- 23119126
TI  - Comparison of an imaging software and manual prediction of soft tissue changes
      after orthognathic surgery.
AB  - OBJECTIVE: Accurate prediction of the surgical outcome is important in treating
      dentofacial deformities. Visualized treatment objectives usually involve manual
      surgical simulation based on tracing of cephalometric radiographs. Recent
      technical advancements have led to the use of computer assisted imaging systems
      in treatment planning for orthognathic surgical cases. The purpose of this study
      was to examine and compare the ability and reliability of digitization using
      Dolphin Imaging Software with traditional manual techniques and to compare
      orthognathic prediction with actual outcomes. MATERIALS AND METHODS: Forty
      patients consisting of 35 women and 5 men (32 class III and 8 class II) with no
      previous surgery were evaluated by manual tracing and indirect digitization using
      Dolphin Imaging Software. Reliability of each method was assessed then the two
      techniques were compared using paired t test. RESULT: The nasal tip presented the
      least predicted error and higher reliability. The least accurate regions in
      vertical plane were subnasal and upper lip, and subnasal and pogonion in
      horizontal plane. There were no statistically significant differences between the
      predictions of groups with and without genioplasty. CONCLUSION: Computer
      generated image prediction was suitable for patient education and communication.
      However, efforts are still needed to improve accuracy and reliability of the
      prediction program and to include changes in soft tissue tension and muscle
      strain.

PMID- 23119127
TI  - In vitro evaluation of the effect of core thickness and fabrication stages on the
      marginal accuracy of an all-ceramic system.
AB  - OBJECTIVE: To evaluate the influence of core thickness and fabrication stages on
      the marginal accuracy of IPS e.max Press crowns. MATERIALS AND METHODS: Twenty
      IPS e.max Press crowns, 1.5mm thick, were fabricated on metal dies. The crowns
      had two different core thicknesses, 0.8mm for group A and 1mm for group B, ten
      for each group. Marginal gap was measured after each stage of core fabrication,
      veneering and glaze firing. The specimens were not cemented and the measurements
      were made at four points on metal dies using a stereomicroscope (*120). Data were
      analyzed by SPSS software and independent t-test. RESULTS: Mean marginal gaps
      measured after each stage for group A were 13.5 (+/-1.4) MUm, 33.9 (+/-2.3) MUm
      and 40.5(+/-1.7) MUm, and for group B these figures were 14.9(+/-2.0) MUm,
      35.5(+/-2.2) MUm and 41.3(+/-2.0) MUm. There were no statistically significant
      differences in marginal gap values between the two groups (p>0.1). Significant
      increase in gap was observed after the veneering stage in both groups (p<0.05).
      After glazing, no significant increase in gap was detected. CONCLUSION: IPS e.max
      Press crowns have an acceptable marginal fit. Increasing thickness of core does
      not increase marginal fitness.

PMID- 23119128
TI  - Periodontal disease status in an isolated greek adult population.
AB  - OBJECTIVE: The aim of the present study was to examine the periodontal condition
      of an adult population in three isolated regions in Greece and to determine the
      association of periodontal disease with several demographic, behavioral and
      environmental factors. MATERIALS AND METHODS: The study population consisted of
      640 individuals, aged 20 to 69 years from three isolated regions. The following
      indices were assessed: Pocket Depth (PD), Clinical Attachment Level (CAL), Dental
      Plaque, Calculus and Bleeding on Probing (BOP). Statistical analysis was
      accomplished by multiple linear regression model which was used to assess the
      association between the mean clinical attachment loss and clinical, demographic
      and behavioral parameters. RESULTS: The samples of the study showed high levels
      of dental plaque, dental calculus and BOP. The final multivariate model showed
      that age (p=0.000), gender (p=0.016) and presence of calculus (p=0.000) were
      associated with the mean clinical attachment loss. Age (p=0.000), gender
      (p=0.000) and dental plaque (p=0.027) were associated with gingival recession,
      while age (p=0.018) and gender (p=0.000) were associated with probing depth.
      Bleeding on probing, dental plaque, toothbrush frequency, level of education,
      tobacco consumption and reasons for dental visits were not associated with the
      mean clinical attachment loss. CONCLUSION: Periodontal disease consists of a
      complicated destructive condition of the Periodontal tissue with a. multi
      factorial etiology. Oral hygiene instructions and a regular dental follow-up
      could play a significant role in the prevention of periodontal disease.

PMID- 23119129
TI  - Interdental spacing and dental caries in the primary dentition of 4-6 year old
      children.
AB  - OBJECTIVE: There are various risk factors which play an essential role in the
      multifactorial disease "dental caries." Although absence of interdental spaces in
      the primary dentition may increase the risk of dental caries, not many studies
      have been carried out to assess this correlation. This study was performed to
      assess the relationship between interdental spacing and dental caries in primary
      dentition. MATERIALS AND METHODS: Five hundred 4-6 year-old children were
      enrolled into this study. Dental caries was recorded using the criteria given by
      Warren et al. Following this, impressions were made for the upper and lower
      arches and dental casts were poured. Interdental spaces were measured on the
      dental casts using a digital verniercaliper. The data obtained were subjected to
      statistical analysis. RESULTS: The number of sites with interdental spaces was
      higher in the maxillary arch in comparison to the mandibular arch. The highest
      number of interdental spaces was observed between the maxillary anteriors. The
      number of demineralized, but non-cavitated tooth surfaces (d(1))were higher than
      the number of cavitated tooth surfaces. This difference was significant in the
      mandibular anterior segment. Dental caries showed a negative correlation with
      interdental spacing. A significant correlation was found between dental caries
      and interdental spacing in the posterior segment of the mandibular arch.
      CONCLUSION: This study showed that children with no interdental spacing in the
      primary dentition are at higher risk for dental caries.

PMID- 23119130
TI  - Comparison of Microleakage of Glass Ionomer Restoration in Primary Teeth Prepared
      by Er: YAG Laser and the Conventional Method.
AB  - OBJECTIVE: One of the main criteria in evaluating the restorative materials is
      the degree of microleakage. The aim of this study was to compare the microleakage
      of glass ionomer restored cavities prepared by Er:YAG laser or turbine and bur.
      MATERIALS AND METHODS: Twenty extracted caries-free deciduous posterior teeth
      were selected for this study. The teeth were randomly divided into two groups for
      cavity preparation. Cavities in group one were prepared by high speed turbine and
      bur. In the second group, Er:YAG laser with a 3W output power, 300 mJ energy and
      10 Hz frequency was used. Cavities were restored with GC Fuji II LC. After
      thermocycling, the samples were immersed into 0.5% methylene blue solution. They
      were sectioned for examination under optic microscope. RESULTS: The Wilcoxon
      signed ranks test showed no significant difference between microleakage of the
      laser group and the conventional group (P>0.05). CONCLUSION: Er:YAG laser with
      its advantages in pediatric dentistry may be suggested as an alternative device
      for cavity preparation.

PMID- 23119131
TI  - Effect of high water fluoride concentration on the intellectual development of
      children in makoo/iran.
AB  - OBJECTIVE: Prolonged excessive intake of fluoride during child's growth and
      development stages has been associated with mental and physical problems. The aim
      of this study was to investigate the effect of excessive fluoride intake on the
      intelligence quotient (IQ) of children living in five rural areas in Makoo/Iran.
      MATERIALS AND METHODS: In this cross-sectional study, 293 children aged 6-11
      years were selected from five villages in Makoo with normal fluoride (0.8+/-0.3
      ppm), medium fluoride (3.1+/-0.9 ppm) and high fluoride (5.2+/-1.1 ppm) in their
      water supplies. The IQ of each child was measured by the Raven's test.
      Educational and residential information and the medical history of each child was
      recorded by a questionnaire completed by the parents. Data were analyzed by ANOVA
      test with a significance level of 0.05. RESULTS: The mean IQ scores decreased
      from 97.77+/-18.91 for the normal fluoride group to 89.03+/-12.99 for the medium
      fluoride group and to 88.58+/-16.01 for the high fluoride group (P=0.001).
      CONCLUSION: Children residing in areas with higher than normal water fluoride
      levels demonstrated more impaired development of intelligence. Thus, children's
      intelligence may be affected by high water fluoride levels.

PMID- 23119132
TI  - The effect of ascorbic Acid on the substantivity of tetraclean in sodium
      hypochlorite-treated bovine dentin.
AB  - OBJECTIVE: The purpose of this study was to assess the in vitro effect of
      ascorbic acid on the antibacterial substantivity of Tetraclean in bovine root
      dentin pretreated with sodium hypochlorite (NaOCl). MATERIALS AND METHODS: Eighty
      dentin tubes prepared from bovine incisor teeth were infected with Enterococcus
      faecalis for 14 days. The specimens were divided into five groups as follows:
      Tetraclean; 5.25% NaOCl/Tetraclean; 5.25% NaOCl/ascorbic acid/Tetraclean;
      infected dentin tubes (positive control); and sterile dentin tubes (negative
      control). At experimental times of 0, 7, 14, 21 and 28 days, dentin chips were
      removed from the canals by sequential sterile low-speed round burs with
      increasing diameters of 025, 027, 029, 031 and 033 ISO sizes, respectively. After
      culturing, the number of colony-forming units (CFU) was counted. RESULTS: In all
      experimental groups, the number of CFU was minimum in the first cultures and the
      results obtained were significantly different at any time period (p < 0.05). The
      Tetraclean group showed the most effective antibacterial action at all five
      experimental periods (p < 0.05). NaOCl/Tetraclean group showed the least
      antibacterial activity at all time periods. The NaOCl/ascorbic acid/Tetraclean
      group showed similar antibacterial substantivity to the Tetraclean group at all
      time periods (p> 0.05). CONCLUSION: Ascorbic acid prevents the decrease of
      residual antibacterial activity of Tetraclean in dentin samples pretreated with
      NaOCl.

PMID- 23119133
TI  - Comparison of lateral window and osteotome techniques in sinus augmentation:
      histological and histomorphometric evaluation.
AB  - OBJECTIVE: The aim of this study was to compare the lateral window and osteotome
      techniques for sinus lifting using histological and histomorphometric methods.
      MATERIALS AND METHODS: In this clinical trial 10 patients (a total number of 14
      sinus areas) who needed implant treatment in the atrophic posterior maxilla were
      enrolled. In all the cases the residual bone height between the sinus floor and
      the alveolar crest was less than 5 mm. Sinus augmentation was performed. The
      treatment modality for a given residual bone height was selected randomly and Bio
      Oss was applied in all the cases as the graft material. After a healing period of
      about 10 months, in all the cases, the implants were placed and biopsies of
      alveolar crestal bone were obtained at the same time; biopsy specimens were
      evaluated using histological and histomorphometric methods. Fisher's exact and
      Mann-Whitney U tests were used to compare distribution of variables in the two
      groups. Statistical significance was defined at P<0.05. RESULTS: The new bone was
      located in direct contact with the biomaterial without any gaps. This viable bone
      consisted of lacunae containing osteocytes. Infiltration of inflammatory cells
      did not exhibit any significant differences between the two techniques. Foreign
      body reaction was not observed in any cases. Histomorphometric evaluations
      demonstrated that The mean values of the new bone in the lateral window and
      osteotome techniques were 30+/-6.0 and 25.2+/-5.2, respectively, with no
      significant differences between the two groups.. Moreover, the average quantity
      of residual biomaterial and connective tissue were similar for the two groups.
      CONCLUSION: The nature and the volume of the new bone in lateral window and
      osteotome techniques were the same.

PMID- 23119134
TI  - Orthodontic treatment and the oral health-related quality of life of patients.
AB  - OBJECTIVE: Malocclusion is a common oral disorder, can cause negative impacts on
      oral conditions, social life and patients' self confidence. The objective of this
      study was to determine whether orthodontic treatment influence oral health
      related quality of life (OHQoL). MATERIALS AND METHODS: Cross-sectional design
      with self-reported data were collected from 302 participants attended at
      professional orthodontic office (62% female; mean age, 21.71 years) in two
      "treatment" and "no treatment" groups. The measure namely (oral health impact
      profile) OHIP-14 was used to assess the patient's OHQol. Linear regression model
      was used in the data analysis. RESULTS: A significant relationship was found in
      one question and one domain of OHIP-14 between the two groups (P<0.05) which
      showed difference in physical limitation. Linear regression model showed that in
      the treatment group, this domain of OHQoL was 1.86 times less likely complicated
      than in the "no treatment" group. CONCLUSION: Patients who had completed
      orthodontic treatment had a better OHQoL in physical aspects than those who never
      had treatment.

PMID- 23119135
TI  - Comparative depth of cure among two light-cured core build-up composites by
      surface vickers hardness.
AB  - OBJECTIVE: Depth of cure of composite material is restricted and it depends on
      many parameters such as thickness. The aim of this in-vitro study was to evaluate
      the depth of cure of two light-cured core build-up composites (Quixfil and
      Photocore) in different thicknesses, when cured for 60 seconds. MATERIALS AND
      METHODS: The Vickers microhardness measurements were made for each side of the
      top irradiated surfaces of 1,2,3,4,5,6,7 and 8-mm-thick cylindrical blocks of two
      core build-up light-cured composites (Quixfil and Photocore) and a micro hybrid
      composite (Z250) as the control group. For each thickness a bottom to top Vickers
      Hardness Number (VHN) ratio was determined and a value of at least 80% was used
      to indicate the acceptable depth of curing. The results were analyzed with two
      way ANOVA and Tukey HSD test. P value<0.05 was considered significant. RESULTS: A
      two way ANOVA indicated that both the depth of cure and VHN were significantly
      influenced by composite type (P< 0.001) and thickness (P< 0.001). The bottom to
      top VHN ratio reflecting the relative curing degree showed acceptable curing at a
      depth of 5 mm for Quixfil and Photocore; however, it was 3 mm for Z250. The
      surface micro hardness of Photocore was significantly higher than the other
      materials in all thicknesses. CONCLUSION: Although both two composites can be
      bulk cured, their curing depths were lower than that was expected. Curing depth
      is a property which is material specific and decreases with thickness (P <
      0.001).

PMID- 23119136
TI  - New method for fabrication of gunning splint in orthognathic surgery for
      edentulous patients.
AB  - Treatment planning poses difficulties in edentulous patients for orthognathic
      surgery prediction and fixation.Treatment of severe class III malocclusion
      frequently requires orthognathic surgical procedures. For such patients,
      orthognathic surgery would be the only option before prosthetic
      rehabilitation.This clinical report describes step-by-step fabrication of a
      surgical splint for an edentulous 22-year-old patient with a severe class III
      malocclusion.The patient wound up in class I occlusions and stable prosthodontic
      rehabilitation.Using splints for planning and guiding the surgery in edentulous
      patients facilitates accurate positioning of the jaws and saves time in the
      operating room.

PMID- 23119137
TI  - Abnormal dentition in a boy with incontinentia pigmenti: case report.
AB  - Incontinentia pigmenti (IP) is an X-linked dominant genodermatosis characterized
      by typical skin lesions along Blaschko's lines and associated with ocular,
      dental, nails, hair, skeletal, central nervous system and cardiovascular
      anomalies. We report a 5-year-old boy with cutaneous hyperpigmentation along
      Blaschko's lines, atrophic streaks, strabismus and mental retardation. He showed
      the characteristic abnormal dentition seen in IP as partial hypodontia, peg
      shaped anterior teeth and un-erupted teeth. The expression of IP in boys is
      exceptional as the disease is lethal in males.

PMID- 23119139
TI  - Reversible conversion of epithelial and mesenchymal phenotypes in SV40 large T
      antigen-immortalized rat liver cell lines.
AB  - EMT (epithelial-mesenchymal transition) is a key process in the development of
      liver fibrosis. This process is also essential for liver morphogenesis in
      embryonic development. To study the cellular and molecular basis of EMT, we
      established two phenotypically different SV40 large T antigen-immortalized cell
      lines from rat hepatocytes. The first cell line, which had an epithelial
      morphology and was established in DMEM (Dulbecco's modified Eagle's medium)/Ham's
      F-12 (DF)-based medium (RL/DF cells), expressed CK18 (cytokeratin 18), a marker
      of parenchymal hepatocytes. The other, a mesenchymal-like cell line established
      in DMEM-based medium (RL/DMEM cells), expressed alphaSMA (alpha-smooth muscle
      actin), a marker of hepatic myofibroblasts. Epithelial RL/DF cells underwent
      phenotypic changes, such as increased expression of alphaSMA, when the culture
      medium was switched to DMEM-based medium. In contrast, mesenchymal RL/DMEM cells
      were induced to express the epithelial marker CK18 with a concomitant decrease in
      alphaSMA expression when the culture medium was replaced with DF-based medium.
      These cell lines may provide novel in vitro models for the study of the
      conversion between epithelial and mesenchymal phenotypes during EMT in liver
      fibrosis and morphogenesis.

PMID- 23119138
TI  - Advances in ethylene signalling: protein complexes at the endoplasmic reticulum
      membrane.
AB  - The gaseous plant hormone ethylene plays critical roles in plant responses to
      environmental and endogenous signals that modulate growth and development. Over
      the past 25 years, great progress has been made in elucidating the ethylene
      signalling pathway. Genetic studies in Arabidopsis thaliana have identified key
      components of the pathway, and subcellular localization studies have shown that
      most of these components, other than transcription factors and protein turnover
      machinery, are associated with or lie within the endoplasmic reticulum (ER)
      membrane. The ethylene receptors are found in high-molecular-mass protein
      complexes and interact with the CTR1 serine/threonine protein kinase and the
      genetically downstream EIN2 Nramp-like protein. To more fully understand the
      ethylene signalling pathway, recent research has focused on examining the
      molecular connections between these components and how they are regulated. Here,
      we review recent advances and remaining gaps in our understanding of the early
      steps in the ethylene signalling pathway taking place at the ER.

PMID- 23119140
TI  - Activation of kinase phosphorylation by heat-shift and mild heat-shock.
AB  - Most cells activate intracellular signalling to recover from heat damage. An
      increase of temperature, known as HS (heat shock), induces two major signalling
      events: the transcriptional induction of HSPs (heat-shock proteins) and the
      activation of the MAPK (mitogen-activated protein kinase) cascade. We performed
      the present study to examine the effects of HS, induced by different experimental
      conditions, on various kinases [ERK (extracellular-signal-regulated kinase), JNK
      (c-Jun N-terminal kinase), p38, Akt, AMPK (AMP-activated protein kinase) and PKC
      (protein kinase C)]. We investigated by Western blot analysis the phosphorylation
      of MAPK as a measure of cellular responsiveness to heat shift (37 degrees C) and
      mild HS (40 degrees C) in different cell lines. The results of the study indicate
      that every cell line responded to heat shift, and to a greater extent to HS,
      increasing ERK and JNK phosphorylation, whereas variable effects on activation or
      inhibition of PKC, AMPK, Akt and p38 were observed. Besides the implications of
      intracellular signalling activated by heat variations, these data may be of
      technical relevance, indicating possible sources of error due to different
      experimental temperature conditions.

PMID- 23119141
TI  - Marine sponge depsipeptide increases gap junction length in HTC cells transfected
      with Cx43-GFP.
AB  - Connexins are membrane proteins that form GJ (gap junction) channels between
      adjacent cells. Cx43 (connexin 43), the most widely expressed member of the
      connexin family, has a rapid turnover rate, and its degradation involves both the
      lysosomal and ubiquitin-proteasome pathway. The goal of this work was to study
      the effects of geodiamolides, natural peptides from marine sponge that normally
      are involved with microfilament disruption, on connexin assembly or degradation
      in the plasma membrane. HTC (hepatocarcinoma cells) expressing Cx43-GFP (green
      fluorescent protein) were submitted to treatment with 200 nM geodiamolides A, B,
      H and I for 2 and 4 h. Microfilament distribution and the presence and size of GJ
      plaques were evaluated by laser scanning confocal microscopy. Among the four
      peptides tested, only Geo H (geodiamolide H) statistically enhanced the length of
      GJ plaques. Geodiamolide A also showed activity in the GJ plaque size; however,
      its effect was less pronounced. Treatment with Geo H could interfere with the
      delivery of connexins to the degradation structures, similar to proteasomal
      pathways, keeping the connexins assembled and accumulating GJ plaques. Further
      experiments, with the cells treated with Geo H, using the fungal antibiotic BFA
      (brefeldin A), were performed in order to uncouple events leading to GJ assembly
      from those related to GJ removal, since BFA is known to block protein trafficking
      within a fused ER (endoplasmic reticulum)/Golgi compartment. GJ plaques were
      drastically reduced after BFA/Geo H treatment, thus indicating that Geo H affects
      mainly the delivery pathway of Cx43 protein.

PMID- 23119142
TI  - Down-regulation of TERE1/UBIAD1 activated Ras-MAPK signalling and induced cell
      proliferation.
AB  - TERE1/UBIAD1 is involved in SCCD (Schnyder crystalline corneal dystrophy) and
      multiple human cancers. So far, the molecular mechanism of TERE1/UBIAD1 in
      tumourigenesis is unclear. Here, the expression levels of hTERT and TERE1/UBIAD1
      in pathologically proven Chinese TCC (transitional cell carcinoma) samples were
      measured. It was found that decreased TERE1/UBIAD1 expression is closely related
      to both an increased hTERT expression and activation of Ras-MAPK signalling.
      Chemically modified TERE1 siRNA oligos were used to knock down TERE1 expression
      in human L02 cells. Cells transfected with TERE1 siRNA oligos underwent
      significant cell proliferation. When the levels of hTERT expression and ERK
      phosphorylation were measured, it was found that both of them increased in the
      above transfected cells, suggesting the activation of Ras-MAPK signalling.
      Addition of the MEK inhibitor U0126 into the transfected L02 cells described
      above inhibited ERK phosphorylation and hTERT expression. Our result is the
      initial demonstration that down-regulation of TERE1 activates Ras-MAPK signalling
      and induces subsequent cell proliferation. TERE1 might be a new negative
      regulator of Ras-MAPK signalling, which plays a pivotal role in the cell
      proliferation of multiple human cancers.

PMID- 23119143
TI  - Microarray analysis of ox-LDL (oxidized low-density lipoprotein)-regulated genes
      in human coronary artery smooth muscle cells.
AB  - Recent studies suggest that circulating LDL (low-density lipoproteins) play a
      central role in the pathogenesis of atherosclerosis, and the oxidized form (ox
      LDL) is highly atherogenic. Deposits of ox-LDL have been found in atherosclerotic
      plaques, and ox-LDL has been shown to promote monocyte recruitment, foam cell
      formation and the transition of quiescent and contractile vascular SMCs (smooth
      muscle cells) to the migratory and proliferative phenotype. SMC phenotype
      transition and hyperplasia are the pivotal events in the pathogenesis of
      atherosclerosis. To comprehend the complex molecular mechanisms involved in ox
      LDL-mediated SMC phenotype transition, we have compared the differential gene
      expression profiles of cultured quiescent human coronary artery SMCs with cells
      induced with ox-LDL for 3 and 21 h using Affymetrix HG-133UA cDNA microarray
      chips. Assignment of the regulated genes into functional groups indicated that
      several genes involved in metabolism, membrane transport, cell-cell interactions,
      signal transduction, transcription, translation, cell migration, proliferation
      and apoptosis were differentially expressed. Our data suggests that the
      interaction of ox-LDL with its cognate receptors on SMCs modulates the induction
      of several growth factors and cytokines, which activate a variety of
      intracellular signalling mechanisms (including PI3K, MAPK, Jak/STAT, sphingosine,
      Rho kinase pathways) that contribute to SMC transition from the quiescent and
      contractile phenotype to the proliferative and migratory phenotype. Our study has
      also identified several genes (including CDC27, cyclin A1, cyclin G2, glypican 1,
      MINOR, p15 and apolipoprotein) not previously implicated in ox-LDL-induced SMC
      phenotype transition and substantially extends the list of potential candidate
      genes involved in atherogenesis.

PMID- 23119144
TI  - Effects of different elicitors on 10-deacetylbaccatin III-10-O-acetyltransferase
      activity and cytochrome P450 monooxygenase content in suspension cultures of
      Taxus cuspidata cells.
AB  - The effects of four elicitors, including 100 MUmol/l MeJA (methyl jasmonate), 40
      MUl/l hydrogen peroxide (30%, w/w), 80 mg/l SA (salicylic acid) and 0.4 g/l F3
      (fungal elicitor), on suspension cultures of Taxus cuspidata were studied. After
      addition of the above four elicitors, the enzyme activity of 10-DBAT (10
      deacetylbaccatin III-10-O-acetyltransferase) was induced and reached its maximum
      of 5.47, 0.97, 3.30 and 6.82 U, respectively. After elicitation, the
      concentrations of cytochrome P450 monooxygenase were also induced to its maximum
      values of 0.069, 0.336, 0.321 and 0.193 nmol/ml, respectively. In addition, under
      the elicitation, the change in 10-DBAT activity was similar to that of cytochrome
      P450 monooxygenase concentration. The products of these two enzymes changed after
      the variety of the enzymes, and the taxol content increased through the
      cultivation.

PMID- 23119145
TI  - Establishment of glass catfish (Kryptopterus bicirrhis) fin-derived cells.
AB  - Genetically manipulated transparent animals were already explored in many species
      for in vivo study of gene expression, transplantation analysis and cancer
      biology. However, there are no reports about transparent animals as in vitro
      genetic resources. In the present study, fin-derived cells from glass catfish
      (Krytopterus bicirrhis), naturally transparent fish with a visible skeleton and
      internal organs, were isolated after culturing fin explants and characterized
      using cryopreservation and cell cycle analysis. The cells grew well in DMEM
      (Dulbecco's modified Eagle's medium) containing 1% (v/v) P/S (penicillin
      streptomycin) and 10% (v/v) fetal bovine serum at 26 degrees C and showed
      increased cryopreservation efficiency with the slow-freezing method in the
      presence of 15% dimethyl sulfoxide. In addition, cell cycle analysis was
      evaluated based on flow cytometric analysis, and culturing to confluence (>85%)
      was more effective for synchronizing cells at the G(0)/G(1) stages than
      roscovitine treatment (<75%). This is the first report about cell isolation from
      transparent animals. The results from testing the cell's viability following
      cryopreservation and subjecting the cells to cycle analysis can be useful tools
      for genetic resource management.

PMID- 23119146
TI  - Selective silencing of DNA topoisomerase IIbeta in human mesenchymal stem cells
      by siRNAs (small interfering RNAs).
AB  - hMSCs (human mesenchymal stem cells) express two isoforms of DNA topo II
      (topoisomerase II). Although both isoforms have the same catalytic activity, they
      are specialized for different functions in the cell: while topo IIalpha is
      essential for chromosome segregation in mitotic cells, topo IIbeta is involved in
      more specific cellular functions. A number of inhibitors are available that
      inhibit the catalytic activity of both topo II isoforms. However, in order to
      investigate the isoform-specific inhibition of these two enzymes, it is necessary
      to use other techniques such as siRNA (small interfering RNA) interference to
      selectively silence either one of the isoforms individually. Depending on the
      lipid charge densities and protein varieties of the cell membrane, previous
      studies have demonstrated that transfection efficiencies of siRNAs to hMSCs are
      very low. In the study reported here, we demonstrate the use of Lipofectamine
      RNAiMAX as an efficient transfection reagent to introduce siRNAs into human
      mesenchymal stem cells with significantly great efficiency to silence topo IIbeta
      selectively. A high level of transfection efficiency (80%) was achieved by using
      unlabelled topo IIbeta-specific siRNA oligos. Specifically, it was confirmed
      repeatedly that green labelled siRNAs interfere with the transfection of siRNAs.
      The reagent induced minimal cytotoxicity (3.5-4.5%), and cell viability of the
      transfected hMSCs decreased 20-30% compared with untreated cells, depending on
      the concentration of the reagent.

PMID- 23119147
TI  - Indications of optical coherence tomography in keratoplasties: literature review.
AB  - Optical coherence tomography (OCT) of the anterior segment, in particular corneal
      OCT, has become a reliable tool for the cornea specialist, as it provides the
      acquisition of digital images at high resolution with a noncontact technology. In
      penetrating or lamellar keratoplasties, OCT can be used to assess central corneal
      thickness and pachymetry maps, as well as precise measurements of deep stromal
      opacities, thereby guiding the surgeon to choose the best treatment option. OCT
      has also been used to evaluate the keratoplasty postoperative period, for early
      identification of possible complications, such as secondary glaucoma or donor
      disc detachments in endothelial keratoplasties. Intraoperatively, OCT can be used
      to assess stromal bed regularity and transparency in anterior lamellar surgeries,
      especially for those techniques in which a bare Descemet's membrane is the goal.
      The purpose of this paper is to review and discuss the role of OCT as a
      diagnostic tool in various types of keratoplasties.

PMID- 23119148
TI  - Diabetes and coronary heart disease: a risk factor for the global epidemic.
AB  - Cardiovascular disease remains a leading cause of death in the United States and
      the world. In this we will paper focus on type 2 diabetes mellitus as a risk
      factor for coronary heart disease, review the mechanisms of atherogenesis in
      diabetics, the impact of hypertension and the treatment goals in diabetics, the
      guidelines for screening, and review the epidemiologic consequences of diabetes
      and heart disease on a global scale. The underlying premise to consider diabetes
      a cardiovascular disease equivalent will be explored as well as the
      recommendations for screening and cardiac testing for asymptomatic diabetic
      patients.

PMID- 23119150
TI  - Relationship of Lifestyle Medical Advice and Non-HDL Cholesterol Control of a
      Nationally Representative US Sample with Hypercholesterolemia by Race/Ethnicity.
AB  - Objective. The main purpose of this study was to evaluate the associations of
      lifestyle medical advice and non-HDL cholesterol control of a nationally
      representative US sample of adults with hypercholesterolemia by race/ethnicity.
      Methods. Data were collected by appending sociodemographic, anthropometric, and
      laboratory data from two cycles of the National Health and Nutrition Survey (2007
      2008 and 2009-2010). This study acquired data from male and female adults aged >=
      20 years (N = 11,577), classified as either Mexican American (MA), (n = 2173),
      other Hispanic (OH) (n = 1298), Black non-Hispanic (BNH) (n = 2349), or White non
      Hispanic (WNH) (n = 5737). Results. Minorities were more likely to report having
      received dietary, weight management, and exercise recommendations by healthcare
      professionals than WNH, adjusting for confounders. Approximately 80% of those
      receiving medical advice followed the recommendation, regardless of
      race/ethnicity. Of those who received medical advice, reporting "currently
      controlling or losing weight" was associated with lower non-HDL cholesterol. BNH
      who reported "currently controlling or losing weight" had higher non-HDL
      cholesterol than WNH who reported following the advice. Conclusion. The results
      suggest that current methods of communicating lifestyle advice may not be
      adequate across race/ethnicity and that a change in perspective and delivery of
      medical recommendations for persons with hypercholesterolemia is needed.

PMID- 23119151
TI  - Prediction of outcome from community-acquired severe sepsis and septic shock in
      tertiary-care university hospital in a developing country.
AB  - Our aim was to determine the risk factors on mortality in adult patients with
      community-acquired severe sepsis and septic shock. The main outcome measure was
      hospital mortality. This prospective single centre study was conducted from
      January 1, 2008 to December 31, 2010, and included 184 patients, of whom 135
      (73.4%) were with severe sepsis and 49 (26.6%) had septic shock. Overall, ninety
      five (51.6%) patients have died, 60 (44.4%) in severe sepsis and 35 (71.4%)
      patients with septic shock. The lung was the most common site of infection 121
      (65.8%), and chronic heart failure was the most frequent comorbidity 65 (35.3%).
      Logistic multivariate analysis identified three independent risk factors for
      mortality in patients with severe sepsis: positive blood culture (odds ratio,
      2.39; 95% confidence interval, 1.13-5.06; P = 0.02), three or more organ
      dysfunctions (odds ratio, 3.93; 95% confidence interval, 1.62-9.53; P = 0.002),
      and Simplified Acute Physiology Score (SAPS) II (odds ratio, 1.02; 95% confidence
      interval, 1.00-1.04; P = 0.01). In addition to SAPS II, positive blood culture,
      and three or more organ dysfunctions are important independent risk factors for
      mortality in patients with severe sepsis and septic shock.

PMID- 23119152
TI  - Human versus Computer Controlled Selection of Ventilator Settings: An Evaluation
      of Adaptive Support Ventilation and Mid-Frequency Ventilation.
AB  - Background. There are modes of mechanical ventilation that can select ventilator
      settings with computer controlled algorithms (targeting schemes). Two examples
      are adaptive support ventilation (ASV) and mid-frequency ventilation (MFV). We
      studied how different clinician-chosen ventilator settings are from these
      computer algorithms under different scenarios. Methods. A survey of critical care
      clinicians provided reference ventilator settings for a 70 kg paralyzed patient
      in five clinical/physiological scenarios. The survey-derived values for minute
      ventilation and minute alveolar ventilation were used as goals for ASV and MFV,
      respectively. A lung simulator programmed with each scenario's respiratory system
      characteristics was ventilated using the clinician, ASV, and MFV settings.
      Results. Tidal volumes ranged from 6.1 to 8.3 mL/kg for the clinician, 6.7 to
      11.9 mL/kg for ASV, and 3.5 to 9.9 mL/kg for MFV. Inspiratory pressures were
      lower for ASV and MFV. Clinician-selected tidal volumes were similar to the ASV
      settings for all scenarios except for asthma, in which the tidal volumes were
      larger for ASV and MFV. MFV delivered the same alveolar minute ventilation with
      higher end expiratory and lower end inspiratory volumes. Conclusions. There are
      differences and similarities among initial ventilator settings selected by humans
      and computers for various clinical scenarios. The ventilation outcomes are the
      result of the lung physiological characteristics and their interaction with the
      targeting scheme.

PMID- 23119153
TI  - Systemic and urinary neutrophil gelatinase-associated lipocalins are poor
      predictors of acute kidney injury in unselected critically ill patients.
AB  - Background. Neutrophil gelatinase-associated lipocalin (NGAL) in serum and urine
      have been suggested as potential early predictive biological markers of acute
      kidney injury (AKI) in selected critically ill patients. Methods. We performed a
      secondary analysis of a multicenter prospective observational cohort study of
      unselected critically ill patients. Results. The analysis included 140 patients,
      including 57 patients who did not develop AKI, 31 patients who developed AKI, and
      52 patients with AKI on admission to the ICU. Levels of sNGAL and uNGAL on non
      AKI days were significantly lower compared to levels of sNGAL on RIFLE(RISK)
      days, RIFLE(INJURY) days, and RIFLE(FAILURE) days. The AUC of sNGAL for
      predicting AKI was low: 0.45 (95% confidence interval (CI) 0.27-0.63) and 0.53
      (CI 0.38-0.67), 2 days and 1 day before development of AKI, respectively. The AUC
      of uNGAL for predicting AKI was also low: 0.48 (CI 0.33-0.62) and 0.48 (CI 0.33
      0.62), 2 days and 1 day before development of AKI, respectively. AUC of sNGAL and
      uNGAL for the prediction of renal replacement therapy requirement was 0.47 (CI
      0.37-0.58) and 0.26 (CI 0.03-0.50). Conclusions. In unselected critically ill
      patients, sNGAL and uNGAL are poor predictors of AKI or RRT.

PMID- 23119149
TI  - Cholesterol: its regulation and role in central nervous system disorders.
AB  - Cholesterol is a major constituent of the human brain, and the brain is the most
      cholesterol-rich organ. Numerous lipoprotein receptors and apolipoproteins are
      expressed in the brain. Cholesterol is tightly regulated between the major brain
      cells and is essential for normal brain development. The metabolism of brain
      cholesterol differs markedly from that of other tissues. Brain cholesterol is
      primarily derived by de novo synthesis and the blood brain barrier prevents the
      uptake of lipoprotein cholesterol from the circulation. Defects in cholesterol
      metabolism lead to structural and functional central nervous system diseases such
      as Smith-Lemli-Opitz syndrome, Niemann-Pick type C disease, and Alzheimer's
      disease. These diseases affect different metabolic pathways (cholesterol
      biosynthesis, lipid transport and lipoprotein assembly, apolipoproteins,
      lipoprotein receptors, and signaling molecules). We review the metabolic pathways
      of cholesterol in the CNS and its cell-specific and microdomain-specific
      interaction with other pathways such as the amyloid precursor protein and discuss
      potential treatment strategies as well as the effects of the widespread use of
      LDL cholesterol-lowering drugs on brain functions.

PMID- 23119154
TI  - Direct health care costs of treating seasonal affective disorder: a comparison of
      light therapy and fluoxetine.
AB  - Objective. To compare the direct mental health care costs between individuals
      with Seasonal Affective Disorder randomized to either fluoxetine or light
      therapy. Methods. Data from the CANSAD study was used. CANSAD was an 8-week
      multicentre double-blind study that randomized participants to receive either
      light therapy plus placebo capsules or placebo light therapy plus fluoxetine.
      Participants were aged 18-65 who met criteria for major depressive episodes with
      a seasonal (winter) pattern. Mental health care service use was collected for
      each subject for 4 weeks prior to the start of treatment and for 4 weeks prior to
      the end of treatment. All direct mental health care services costs were analysed,
      including inpatient and outpatient services, investigations, and medications.
      Results. The difference in mental health costs was significantly higher after
      treatment for the light therapy group compared to the medication group-a
      difference of $111.25 (z = -3.77, P = 0.000). However, when the amortized cost of
      the light box was taken into the account, the groups were switched with the
      fluoxetine group incurring greater direct care costs-a difference of $75.41 (z = 
      2.635, P = 0.008). Conclusion. The results suggest that individuals treated with
      medication had significantly less mental health care cost after-treatment
      compared to those treated with light therapy.

PMID- 23119155
TI  - Beliefs and Attitudes about Childhood Epilepsy among School Teachers in Two
      Cities of Southeast Brazil.
AB  - Childhood epilepsy is a chronic neurological disorder associated with profound
      psychosocial limitations epileptic children's routine. Lack of information and
      inappropriate beliefs are still the factors that most contribute to the stigma
      and discrimination. This study aimed at characterizing teacher's beliefs and
      attitudes at regular and special schools in two cities of southeastern Brazil
      where students with epilepsy studied. Fifty-six teachers of public regular
      schools and specialized educational institutions for children with disabilities
      from two cities of Southeast Brazil who had epileptic children in their classroom
      completed the Brazilian version of The Epilepsy Beliefs and Attitudes Scale:
      Adult Version and answered a data sheet about sociodemographic characteristics.
      The results showed that no significant differences (P <= 0.05) have been found
      between the beliefs and attitudes of teachers in mainstream and special schools
      but both schoolteachers had more inappropriate beliefs and attitudes than
      appropriate ones against childhood epilepsy. These findings raise an important
      issue, providing us with the knowledge that epilepsy is still a condition which
      is surrounded by wrong beliefs. Also, educational programs could help reduce the
      gaps in knowledge about how such disease has been perceived worldwide.

PMID- 23119156
TI  - Presurgical Weight Is Associated with Pain, Functional Impairment, and Anxiety
      among Gastric Bypass Surgery Patients.
AB  - Chronic pain and obesity are significant public health concerns in the United
      States associated with significant levels of health-care expenses and lost
      productivity. Previous research suggests that obesity is a risk factor for
      chronic pain, mainly due to excessive weight placed on the joints. However, the
      obesity-pain relationship appears to be complex and reciprocal. Little work to
      date has focused on the relationship between weight and pain among patients
      undergoing gastric bypass surgery for weight loss. Patients scheduled to undergo
      bariatric surgery for weight loss at a large southeastern academic medical center
      (N = 115) completed the Brief Pain Inventory (BPI), the Center for
      Epidemiological Studies 10-item Depression scale (CESD-10), and the Beck Anxiety
      Inventory (BAI). Higher presurgical weight was associated with higher pain-on
      average ratings, higher functional impairment due to pain across the domains of
      physical activity, mood, walking ability, relationships, and enjoyment of life.
      Higher presurgical weight was associated with higher BAI scores, but weight was
      not related to depression. Findings suggest that bariatric surgery candidates
      report a moderate amount of pain prior to surgery and that presurgical weight is
      associated with higher pain, increased functional impairment due to pain, and
      increased anxiety. Anxiety was found to mediate the relationship between
      increased weight and pain.

PMID- 23119157
TI  - Quantitative Longitudinal Imaging of Vascular Inflammation and Treatment by
      Ezetimibe in apoE Mice by FMT Using New Optical Imaging Biomarkers of Cathepsin
      Activity and alpha(v)beta(3) Integrin.
AB  - Inflammation as a core pathological event of atherosclerotic lesions is
      associated with the secretion of cathepsin proteases and the expression of
      alpha(v)beta(3) integrin. We employed fluorescence molecular tomographic (FMT)
      noninvasive imaging of these molecular activities using cathepsin sensing
      (ProSense, CatB FAST) and alpha(v)beta(3) integrin (IntegriSense) near-infrared
      fluorescence (NIRF) agents. A statistically significant increase in the ProSense
      and IntegriSense signal was observed within the chest region of apoE(-/-) mice (P
      < 0.05) versus C57BL/6 mice starting 25 and 22 weeks on high cholesterol diet,
      respectively. In a treatment study using ezetimibe (7 mg/kg), there was a
      statistically significant reduction in the ProSense and CatB FAST chest signal of
      treated (P < 0.05) versus untreated apoE(-/-) mice at 31 and 21 weeks on high
      cholesterol diet, respectively. The signal of ProSense and CatB FAST correlated
      with macrophage counts and was found associated with inflammatory cells by
      fluorescence microscopy and flow cytometry of cells dissociated from aortas. This
      report demonstrates that cathepsin and alpha(v)beta(3) integrin NIRF agents can
      be used as molecular imaging biomarkers for longitudinal detection of
      atherosclerosis, and cathepsin agents can monitor anti-inflammatory effects of
      ezetimibe with applications in preclinical testing of therapeutics and
      potentially for early diagnosis of atherosclerosis in patients.

PMID- 23119158
TI  - The Influence of Obesity on Patient Reported Outcomes following Total Knee
      Replacement.
AB  - This study retrospectively analysed the effects of obesity as described by Body
      Mass Index (BMI) on patient reported outcomes following total knee replacement.
      Participants (105 females and 66 males) who had undergone surgery under the care
      of a single surgeon were included in the review and were grouped according to
      their preoperative BMI into nonobese (BMI < 30 kg/m(2)), (n = 73) obese (BMI >=
      30 kg/m(2)) (n = 98). Oxford Knee Score (OKS) and Short Form 12 scores (SF12)
      were taken preoperatively and 6 and 12 months after surgery to analyse
      differences between groups in the absolute scores as well as changes from before
      to after surgery. Preoperatively, the obese group had a significantly poorer OKS
      compared to non obese (44.7 versus 41.2, P = 0.003). There were no statistically
      significant group effects on follow-up or change scores of the OKS and SF12.
      Correlations coefficients between BMI and follow-up and change scores were low (r
      < 0.201). There were no significant differences in the number of complications
      and revisions (local wound infection, 6.7% non obese, 11% obese, postoperative
      systemic complication, 8% non obese, 12% obese, revision, 4% nonobese, 3% obese).
      In conclusion, our findings indicate similar degrees of benefits from the surgery
      irrespective of patient BMI.

PMID- 23119160
TI  - Meta-Analysis of Randomized Controlled Trials on Androgens versus Erythropoietin
      for Anaemia of Chronic Kidney Disease: Implications for Developing Countries.
AB  - Androgens which are relatively cheap were used in the treatment of anaemia in
      dialysis patients before the advent of Erythropoietin (EPO). However, there are
      concerns about their efficacy and side effects. Aims. To examine the efficacy and
      harms of androgens for the treatment of anaemia of chronic kidney disease (CKD)
      compared to EPO. Settings and Design. A systematic review and meta-analysis using
      an a priori protocol. Methods and Materials. We searched several databases for
      randomized controlled trials using the key terms anaemia, chronic kidney disease,
      and androgens, without language restrictions. We also searched reference lists of
      relevant articles. Statistical Analysis Used. Data was analyzed using Review
      manger 5 software. We summarized treatment effects as relative risks and mean
      differences, with 95% confidence intervals using a random-effect model. We tested
      for heterogeneity with Chi(2) and the I(2) statistics. Results. We identified
      four eligible trials involving 114 participants, majority (83.33%) of whom were
      males, mostly over 50 years of age. The pooled difference in mean haemoglobin
      between the nandrolone and EPO arms at the end of the trials was -0.11 (CI -0.80
      to 0.58) which is not statistically significant. Conclusions. This meta-analysis
      revealed no difference between nandrolone and EPO for the treatment of anaemia of
      CKD in men over 50 years. Therefore, nandrolone can be used for the treatment of
      anaemia of CKD in this category of patients, in resource-limited countries.
      However, further studies are needed to determine the long-term safety of
      nandrolone in men over 50 years old, as well as its effectiveness and safety in
      females in general, and males less than 50 years of age.

PMID- 23119159
TI  - Silicon, a Possible Link between Environmental Exposure and Autoimmune Diseases:
      The Case of Rheumatoid Arthritis.
AB  - Silicon is one of the most common chemicals on earth. Several compounds such as
      silica, asbestos, silicone or, nanoparticles are built from tetrahedral units
      with silicon as the central atom. Despite these, structural similarities, they
      have rarely been analyzed as a group. These compounds generate significant
      biological alterations that include immune hyperactivation, production of the
      reactive species of oxygen and tissue injury. These pathological processes may
      trigger autoimmune responses and lead to the development of rheumatoid arthritis.
      Populations at risk include those that constantly work in industrial process,
      mining, and agriculture as well as those that undergo silicone implants. Herein a
      review on the main features of these compounds and how they may induce autoimmune
      responses is presented.

PMID- 23119161
TI  - Reconstruction of Sugar Metabolic Pathways of Giardia lamblia.
AB  - Giardia lamblia is an "important" pathogen of humans, but as a diplomonad
      excavate it is evolutionarily distant from other eukaryotes and relatively little
      is known about its core metabolic pathways. KEGG, the widely referenced site for
      providing information of metabolism, does not yet include many enzymes from
      Giardia species. Here we identify Giardia's core sugar metabolism using standard
      bioinformatic approaches. By comparing Giardia proteomes with known enzymes from
      other species, we have identified enzymes in the glycolysis pathway, as well as
      some enzymes involved in the TCA cycle and oxidative phosphorylation. However,
      the majority of enzymes from the latter two pathways were not identifiable,
      indicating the likely absence of these functionalities. We have also found
      enzymes from the Giardia glycolysis pathway that appear more similar to those
      from bacteria. Because these enzymes are different from those found in mammals,
      the host organisms for Giardia, we raise the possibility that these bacteria-like
      enzymes could be novel drug targets for treating Giardia infections.

PMID- 23119162
TI  - Nutrition and aging: nutritional health inequity.

PMID- 23119163
TI  - A critical appraisal of quantitative studies of protein degradation in the
      framework of cellular proteostasis.
AB  - Protein homeostasis, proteostasis, is essential to understand cell function.
      Protein degradation is a crucial component of the proteostatic mechanisms of the
      cell. Experiments on protein degradation are nowadays present in many
      investigations in the field of molecular and cell biology. In the present paper,
      we focus on the different experimental approaches to study protein degradation
      and present a critical appraisal of the results derived from steady-state and
      kinetic experiments using detection of unlabelled and labelled protein
      methodologies with a proteostatic perspective. This perspective allows
      pinpointing the limitations in interpretation of results and the need of further
      experiments and/or controls to establish "definitive evidence" for the role of
      protein degradation in the proteostasis of a given protein or the entire
      proteome. We also provide a spreadsheet for simple calculations of mRNA and
      protein decays for mimicking different experimental conditions and a checklist
      for the analysis of experiments dealing with protein degradation studies that may
      be useful for researchers interested in the area of protein turnover.

PMID- 23119164
TI  - Impact of "sick" and "recovery" roles on brain injury rehabilitation outcomes.
AB  - This study utilizes a multivariate, correlational, expost facto research design
      to examine Parsons' "sick role" as a dynamic, time-sensitive process of "sick
      role" and "recovery role" and the impact of this process on goal attainment (H1)
      and psychosocial distress (H2) of adult survivors of acquired brain injury.
      Measures used include the Brief Symptom Inventory-18, a Goal Attainment Scale,
      and an original instrument to measure sick role process. 60 survivors of ABI
      enrolled in community reentry rehabilitation participated. Stepwise regression
      analyses did not fully support the multivariate hypotheses. Two models emerged
      from the stepwise analyses. Goal attainment, gender, and postrehab
      responsibilities accounted for 40% of the shared variance of psychosocial
      distress. Anxiety and depression accounted for 22% of the shared variance of goal
      attainment with anxiety contributing to the majority of the explained variance.
      Bivariate analysis found sick role variables, anxiety, somatization, depression,
      gender, and goal attainment as significant. The study has implications for ABI
      rehabilitation in placing greater emphasis on sick role processes, anxiety,
      gender, and goal attainment in guiding program planning and future research with
      survivors of ABI.

PMID- 23119166
TI  - Human Sperm Interaction with Staphylococcus aureus: A Molecular Approach.
AB  - Sperm immobilization factor (SIF) causing 100% immobilization of spermatozoa
      isolated from Staphylococcus aureus when characterized using LC-MS (Liquid
      chromatography-mass spectrometry) showed that this 20 kDa protein had peptide
      sequence similarity with hsp-70 protein. It was found to completely (100%)
      inhibit Mg(++) ATPase activity of spermatozoa at concentration of 100 MUg mL(-1).
      Sperm samples treated with SIF also showed reduction in calcium ionophore-induced
      acrosome reaction as compared to control samples (treated with calcium ionophore
      alone). Binding studies of FITC labelled SIF with spermatozoa using fluorescent
      microscopy showed binding of SIF to the surface of spermatozoa indicating the
      presence of SIF binding receptor. The receptor was extracted by 3M NaCl and
      purified by gel permeation chromatography. Characterization of the receptor by
      MALDI-TOF (Matrix-assisted laser desorption ionization-time of flight) indicated
      that the receptor shared sequence similarity with MHC class II antigen. A
      calorimetric study showed that the receptor moiety on spermatozoa was specific
      for the purified ligand as binding of the receptor to ligand was enthalpically (
      11.9 kJ mole(-1)) as well as entropically (21.53 J mole(-1) K(-1)) favored
      resulting in the Gibb's free energy of -18.57 kJ mole(-1).

PMID- 23119167
TI  - In Vitro Propagation of Muna-Muna (Clinopodium odorum (Griseb.) Harley).
AB  - A micropropagation protocol was developed which may assist in the safeguarding
      and augmentation of dwindling natural populations of Clinopodium odorum (Griseb.)
      Harley, a critically and endangered medicinal plant. Factors affecting culture
      initiation bud sprouting and growth, rooting, and acclimatization were studied,
      using nodal segments of in vitro germinated seedling as primary explants on six
      media supplemented with different concentrations and combinations of 6
      benzylaminopurine (BAP) (0.5-1.5 and 2-Naphthalene acetic acid (NAA) (0.5-1.5).
      Best results for culture initiation with sustainable multiplication rates (100%)
      were obtained on WP medium without any growth regulator. WP with the addition of
      0.5 : 1 or 0.5 : 1.5) of BAP and NAA promoted a higher elongation; however, the
      optimum number of nodes were obtained in plantlets grown on 1/2 MS with the
      addition of 1 : 1.5 of BAP and NAA. Culture of sectioned individual nodes
      transferred to the media with different rates of BAP and NAA 1/2 MS-9 (1.5 :
      1.5), SH-8 (1.5 : 1.0), and 1/2 B5-4 (1.0 : 0.5) media resulted in no
      proliferated shoots. The in vitro plants were successfully acclimatized garden
      soil and sand (2 : 1) in the greenhouse, with over 90% survival rate. The in
      vitro-grown plants could be transferred to ex vitro conditions and the efficacy
      in supporting ex vitro growth was assessed, with a view to develope longer-term
      strategies for the transfer and reintroduction into natural habitats.

PMID- 23119165
TI  - NOD2 Polymorphisms and Their Impact on Haematopoietic Stem Cell Transplant
      Outcome.
AB  - Haematopoietic stem cell transplantation (HSCT) is a valuable tool in the
      treatment of many haematological disorders. Advances in understanding HLA
      matching have improved prognoses. However, many recipients of well-matched HSCT
      develop posttransplant complications, and survival is far from absolute. The
      pursuit of novel genetic factors that may impact on HSCT outcome has resulted in
      the publication of many articles on a multitude of genes. Three NOD2
      polymorphisms, identified as disease-associated variants in Crohn's disease, have
      recently been suggested as important candidate gene markers in the outcome of
      HSCT. It was originally postulated that as the clinical manifestation of
      inflammatory responses characteristic of several post-transplant complications
      was of notable similarity to those seen in Crohn's disease, it was possible that
      they shared a common cause. Since the publication of this first paper, numerous
      studies have attempted to replicate the results in different transplant settings.
      The data has varied considerably between studies, and as yet no consensus on the
      impact of NOD2 SNPs on HSCT outcome has been achieved. Here, we will review the
      existing literature, summarise current theories as to why the data differs, and
      suggest possible mechanisms by which the SNPs affect HSCT outcome.

PMID- 23119168
TI  - The Value of Combined Large Format Histopathology Technique to Assess the
      Surgically Removed Breast Tissue following Neoadjuvant Chemotherapy: A Single
      Institution Study of 40 Cases.
AB  - Historically, neoadjuvant chemotherapy has been used to treat patients with
      advanced breast disease in an attempt to convert them into candidates for breast
      conservation surgery. The ultimate goal of histopathologic examination of the
      specimens removed after neoadjuvant chemotherapy is the identification of either
      residual disease or positive identification of the tumor bed. We report a series
      of 40 patients treated with neoadjuvant chemotherapy and evaluation of the
      surgical specimens by a combination of standard histopathology and the use of
      large format histopathology techniques.

PMID- 23119169
TI  - Calcium signalling and liver regeneration.
AB  - After partial hepatectomy (PH) the initial mass of the organ is restored through
      a complex network of cellular interactions that orchestrate both proliferative
      and hepatoprotective signalling cascades. Among agonists involved in this network
      many of them drive Ca(2+) movements. During liver regeneration in the rat,
      hepatocyte cytosolic Ca(2+) signalling has been shown on the one hand to be
      deeply remodelled and on the other hand to enhance progression of hepatocytes
      through the cell cycle. Mechanisms through which cytosolic Ca(2+) signals impact
      on hepatocyte cell cycle early after PH are not completely understood, but at
      least they include regulation of immediate early gene transcription and ERK and
      CREB phosphorylation. In addition to cytosolic Ca(2+), there is also evidence
      that mitochondrial Ca(2+) and also nuclear Ca(2+) may be critical for the
      regulation of liver regeneration. Finally, Ca(2+) movements in hepatocytes, and
      possibly in other liver cells, not only impact hepatocyte progression in the cell
      cycle but more generally may regulate cellular homeostasis after PH.

PMID- 23119170
TI  - Combined Stimulation with the Tumor Necrosis Factor alpha and the Epidermal
      Growth Factor Promotes the Proliferation of Hepatocytes in Rat Liver Cultured
      Slices.
AB  - The culture liver slices are mainly used to investigate drug metabolism and
      xenobiotic-mediated liver injuries while apoptosis and proliferation remain
      unexplored in this culture model. Here, we show a transient increase in LDH
      release and caspase activities indicating an ischemic injury during the slicing
      procedure. Then, caspase activities decrease and remain low in cultured slices
      demonstrating a low level of apoptosis. The slicing procedure is also associated
      with the G0/G1 transition of hepatocytes demonstrated by the activation of stress
      and proliferation signalling pathways including the ERK1/2 and JNK1/2/3
      MAPKinases and the transient upregulation of c-fos. The cells further progress up
      to mid-G1 phase as indicated by the sequential induction of c-myc and p53 mRNA
      levels after the slicing procedure and at 24 h of culture, respectively. The
      stimulation by epidermal growth factor induces the ERK1/2 phosphorylation but
      fails to activate expression of late G1 and S phase markers such as cyclin D1 and
      Cdk1 indicating that hepatocytes are arrested in mid-G1 phase of the cell cycle.
      However, we found that combined stimulation by the proinflammatory cytokine tumor
      necrosis factor alpha and the epidermal growth factor promotes the commitment to
      DNA replication as observed in vivo during the liver regeneration.

PMID- 23119171
TI  - Sexual health and men who have sex with men in Vietnam: an integrated approach to
      preventive health care.
AB  - Background. While HIV infection among men who have sex with men (MSM) in Vietnam
      has received increasing attention, most studies focus on HIV knowledge and
      established risk factors such as injection drug use. This paper proposes to
      address HIV risk among MSM from an integrated approach to preventive care that
      takes into account syndemic conditions such as substance use, mental health, and
      stigma, the latter of which prevents MSM from accessing health services. Method.
      Current studies related to MSM in Vietnam from 2000 onwards, gathered from peer
      reviewed as well as non-peer-reviewed sources, were examined. Results. HIV and
      STI prevalence among MSM varied significantly by location, and yet HIV prevalence
      has increased significantly over the past few years. Most studies have focused on
      sexual risk behaviors, paying little attention to the broad spectrum of sexual
      health, including noninjecting drug use, heavy alcohol consumption, high rates of
      mental health distress and anxiety, and stigma. Conclusion. Future research and
      interventions targeting MSM in Vietnam should address their vulnerability to HIV
      from an integrated approach that pays attention to both sexual health and
      syndemic conditions.

PMID- 23119172
TI  - In Vitro Effects of External Pressure Changes on the Sealing Ability under
      Simulated Diving Conditions.
AB  - Aim. To measure and validate the permeability of pressure changes in correlation
      to different root filling techniques. Methods. Eighty extracted single-rooted
      teeth were randomly assigned to one of eight groups of ten teeth. Following
      standardized instrumentation and irrigation, root canal fillings were performed
      using either cold lateral condensation, a warm carrier-based gutta-percha
      obturation technique, a warm carrier-based Resilon, or warm gutta-percha
      compaction with the downpack/backfill technique. After insertion of a pressure
      sensor within the pulp chamber ten teeth of each group then underwent simulated
      dives with pressure measurement and the other ten a dye penetration test during
      simulated dives to 5.0 bar. Differences were analyzed statistically (P < 0.05)
      using one-way analysis of variance (ANOVA). Results. When the warm carrier-based
      gutta-percha obturation technique and vertical gutta-percha obturation techniques
      were used, there was significant lower intrapulpal pressure to experimental
      chamber pressure (P > 0.05). When cold lateral condensation or carrier-based
      Resilon as used, pressure was sometimes almost completely equalized. Conclusions.
      Warm gutta-percha obturation techniques provide a largely pressure-tight seal
      whereas the Resilon obturation technique and cold lateral condensation appear to
      be unsuitable to pressure changes.

PMID- 23119173
TI  - pH and Antimicrobial Activity of Portland Cement Associated with Different
      Radiopacifying Agents.
AB  - Objective. The aim of this study was to evaluate the antimicrobial activity and
      pH changes induced by Portland cement (PC) alone and in association with
      radiopacifiers. Methods. The materials tested were pure PC, PC + bismuth oxide,
      PC + zirconium oxide, PC + calcium tungstate, and zinc oxide and eugenol cement
      (ZOE). Antimicrobial activity was evaluated by agar diffusion test using the
      following strains: Micrococcus luteus, Streptococcus mutans, Enterococcus
      faecalis, Pseudomonas aeruginosa, and Candida albicans. After 24 hours of
      incubation at 37 degrees C, inhibition of bacterial growth was observed and
      measured. For pH analysis, material samples (n = 10) were placed in polyethylene
      tubes and immersed in 10 mL of distilled water. After 12, 24, 48, and 72 hours,
      the pH of the solutions was determined using a pH meter. Results. All microbial
      species were inhibited by the cements evaluated. All materials composed of PC
      with radiopacifying agents promoted pH increase similar to pure Portland cement.
      ZOE had the lowest pH values throughout all experimental periods. Conclusions.
      All Portland cement-based materials with the addition of different radiopacifiers
      (bismuth oxide, calcium tungstate, and zirconium oxide) presented antimicrobial
      activity and pH similar to pure Portland cement.

PMID- 23119174
TI  - Evaluation of transfusion pyrexia: a review of differential diagnosis and
      management.
AB  - Background/purpose. Transfusion pyrexia (fever) is an important clinical
      sign/symptom occurring either as an isolated event or as part of a constellation
      of signs and symptoms in relation to blood transfusion. It is an important cause
      of morbidity and may be an important sign of life-threatening complications of
      blood transfusion. Pyrexia is often a reason for the discontinuation of a blood
      transfusion episode, and adequate evaluation remains a challenge for clinicians.
      The decision to stop a blood transfusion episode on account of fever is often a
      difficult one. This paper reviews the differential diagnosis of transfusion
      pyrexia (TP), the pathogenesis as well as current management measures. Study
      selection and data source. Literature sources include medical texts, journals,
      dissertations, and internet-based electronic materials Results and conclusion.
      Adequate evaluation of pyrexia accompanying blood transfusion remains a challenge
      for clinicians. An algorithm to assist the clinician in the evaluation of fever
      occurring in a blood transfusion recipient is developed and presented. Continuous
      medical education is necessary for clinicians towards improved patient care in
      transfusion medicine.

PMID- 23119175
TI  - Comparison between Fluconazole with Oral Protexin Combination and Fluconazole in
      the Treatment of Vulvovaginal Candidiasis.
AB  - Background. According to the limited studies reporting new treatments for
      vulvovaginal candidiasis, this study was designed to compare the combination of
      fluconazole and oral protexin with fluconazole in the treatment of vulvovaginal
      candidiasis. Methods. A double-blind clinical trial was conducted, involving 90
      women who were referred to the gynecology clinic. Vulvovaginal candidiasis was
      diagnosed with itching, cheesy vaginal discharge, and any one of the following:
      dysuria, pH < 4.5, dyspareunia, vulvar erythema, or vulvar edema and if branched
      hyphae and Candida buds were visible after addition of KOH 10% in the culture and
      the result of cultivation in Sabouraud's dextrose agar medium was positive.
      Patients were randomly classified into two groups Absence of discharge, itching,
      and negative culture results 5-7 days after completion of treatment indicated
      treatment success. Data in this study were analyzed using the SPSS version 17.0
      software. Results. The combinations, fluconazole-oral protexin and fluconazole
      placebo, were equally effective in reduction of complaints and symptoms, but
      fluconazole-oral protexin combination elicited a better therapeutic response
      (chi(2) = 0.01, P = 6.7). In addition, fluconazole-oral protexin combination
      treatment demonstrated better recovery time (t = -2.04, P = 0.04). Conclusion.
      This study demonstrated that complementary treatment with probiotic Lactobacillus
      increased the efficacy of fluconazole in treatment of vulvovaginal candidiasis.
      Further research is recommended.

PMID- 23119176
TI  - Epicardial fat tissue thickness in preeclamptic and normal pregnancies.
AB  - Background. Epicardial fat tissue, another form of visceral adiposity, has been
      proposed as a new cardiometabolic risk factor, and the possible association of
      epicardial fat with hypertension has been shown in some recent studies. Although
      epicardial fat thickness (EFT) is associated with hypertension, the relationship
      between preeclampsia and EFT is still unknown. The purpose of this paper is to
      investigate the association between the echocardiographic EFT and the severity of
      preeclampsia in pregnant women. Methods. Forty women with preeclampsia were
      recruited and thirty-five normal pregnant women were matched for both maternal
      age and gestastional age served as control. The materials were collected
      immediately after delivery of the fetus, before placenta expulsion and before
      clamping of the umblical cord in patients and controls whom were in fasting
      state. Total cholesterol, high-density lipoprotein cholesterol (HDL), and
      triglyceride levels (TG) and low-density-lipoprotein cholesterol (LDL), and
      homeostatic model assessment of insulin resistance (HOMA-IR) levels were
      assessed. EFT was measured by using transthoracic echocardiography. Results.
      Among the preeclamptic women, 12 were diagnosed with severe preeclampsia and 28
      mild preeclampsia. There were no statistically significant differences between
      patients with preeclampsia and normal pregnancy except when they are divided
      according to systolic and diastolic blood pressure, proteinuria levels, and
      parity and EFT levels. Among women with preeclampsia (n = 40), 30% had severe
      disease. Women with mild and severe preeclampsia had significiantly higher blood
      pressures at delivery and earlier gestational ages in comparison to control
      subjects. Although TG, VLDL and LDL, HDL, and HOMA-IR levels (P > 0.05) were
      comparable between preeclampsia and normal pregnancies, EFT levels were
      significiantly higher in patients with preeclampsia. Moreover, in subgroup
      analysis, patients with severe preeclampsia had higher EFT levels (P < 0.05) in
      comparison with mild preeclampsia. Conclusions. EFT levels measured at delivery
      were increased in patients with preeclampsia, and patients with increased levels
      of EFT levels had a substantially higher probability of the disease severity in
      comparison to those with mild preeclampsia and controls.

PMID- 23119177
TI  - Results of second-look laparotomy in advanced ovarian cancer: one single center
      experience.
AB  - Objective. The goal of the study was to analyse the results of 85 cases of second
      look laparotomy (SLL) and explore the influence of this procedure on survival.
      Patients and Methods. We reviewed retrospectively 85 cases of SLL collected and
      treated in our institute between 1994 and 2003. Results. Complete pathologic
      response (CPR) was 25.8%, microscopic disease (Rmicro) was 38.8%, and macroscopic
      disease (Rmacro) was 35.4%. In patients with negative SLL results, disease
      recurrence was diagnosed in 41%. The 3- and 5-year overall survival rates for the
      entire population were 91% and 87%, respectively. The 3- and 5-year disease-free
      survivals were, respectively, 76.3% and 58.5% in negative SLL versus 55.7% and
      16% in positive SLL. The difference between the group of patients with complete
      response (76%) and the patients with residual microscopic disease (72%) was not
      significant. The tumoral residuum after initial surgery was the only prognostic
      factor influencing significantly the disease-free survival. On Cox regression
      model analysis, only initial tumoral residuum (P = 0.04) and tumoral residuum
      after SLL (P = 0.02) were independent prognostic factors for survival.
      Conclusions. The most important advantage of SLL is the early detection of
      recurrence and thus the early administration of consolidation treatment resulting
      in a better prognosis.

PMID- 23119178
TI  - Prevalence and Antibiotic Susceptibility of Community-Associated Methicillin
      Resistant Staphylococcus aureus in a Rural Area of India: Is MRSA Replacing
      Methicillin-Susceptible Staphylococcus aureus in the Community?
AB  - Staphylococcus aureus (SA) is the most common cause of skin and soft tissue
      infections (SSTIs) and nosocomial infections. In developed countries there is a
      major concern about the rise of community-associated methicillin-resistant SA (CA
      MRSA), but data from developing countries are scarce. In this study we describe
      the prevalence and antibiotic susceptibility of CA-MRSA and healthcare-associated
      MRSA (HA-MRSA) in a district hospital from rural India. We identified 119 CA-SA
      infections and 82 HA-SA infections. The majority of infections were SSTI, and the
      proportion of MRSA in CA-SA and HA-SA infections was 64.7% and 70.7%,
      respectively. The proportion of CA-MRSA in children <5 years was 73.7%. We did
      not observe any linezolid or vancomycin resistance. CA-SA had high levels of
      resistance to ciprofloxacin and low levels of resistance to chloramphenicol,
      doxycycline, rifampicin, and clindamycin. CA-MRSA had higher proportion of
      resistance to ciprofloxacin, erythromycin, gentamicin, and cotrimoxazole than CA
      methicillin-susceptible SA (CA-MSSA). HA-MRSA had higher proportion of resistance
      to clindamycin and doxycycline than CA-MRSA. The results of this study indicate
      that MRSA is replacing MSSA in CA-SA infections. If these findings are confirmed
      by other studies, the spread of CA-MRSA can be a major public health problem in
      India.

PMID- 23119179
TI  - Treatment of primary axillary hyperhidrosis with botulinum toxin type a: our
      experience in 50 patients from 2007 to 2010.
AB  - Background. Local injections of Botulinum toxin type A (BTX-A) are an effective
      and safe solution for primary bilateral axillary hyperhidrosis. Traditional
      treatments are often ineffective and difficult to tolerate. This study was
      performed to assess the efficacy and safety of Botulinum toxin type A in the
      treatment of these diseases and to evaluate the reliability of patient's
      subjective rating in the timing of repeat injections. Methods. From 2007 to 2008,
      we included in the study and treated a total of 50 patients, and we used the
      Minor's iodine test and the hyperhidrosis diseases severity scale as initial
      inclusion criteria and also for evaluating the followup, comparing to patient's
      subjective rating. We used also a specific questionnaire to evaluate the level of
      pain, the onset of the effect, any eventual adverse effect of the treatment, the
      onset of compensatory hyperhidrosis, and the global grade of satisfaction. The
      data were analyzed using standard statistical methods. Results. 88% of patients
      were totally satisfied and all patients repeated the treatment during all the
      study. The symptom-free interval was in median 6 months with an average improving
      of HDSS of 1.5 points. In 86%, there was a complete accordance between the
      subjective patient's demand of the repetition of the treatment and the positivity
      to Minor test and HDSS. No major side effects happened. Conclusion. Local
      injections of Botulinum toxin type A (BTX-A) result in an effective and safe
      solution for bilateral axillary primary hyperhidrosis for the absence of
      significant morbidity, side effects, and lack of efficacy or duration. The only
      defects are the need of repetition of the treatment and relative costs.

PMID- 23119180
TI  - Patterns and predictors of long-term glycemic control in patients with type 2
      diabetes.
AB  - Aims/Introduction. To describe patterns of long-term glycemic control among
      patients with type 2 diabetes in Isfahan, Iran and identify factors associated
      with glycemic control. Methods. During the mean (standard deviation (SD)) follow
      up period of 8.4 (4.2) (range 1-18) years, 4,582 patients with type 2 diabetes
      have been examined to determine glycemic changes. Their glycated hemoglobin (GHb)
      at the last clinic visit was compared with the initial visit data. The mean (SD)
      age of participants was 49.3 (9.6) years with a mean (SD) duration of diabetes of
      5.0 (5.1) years at initial registration. Results. Mean (SD) GHb was 8.7% (2.3) at
      baseline and 7.9% (1.9) at the study end and decreased by mean of 0.8% (95%
      confidence interval (CI) 0.74, 0.87; P < 0.001) and varied by the severity of
      baseline GHb. 74.6% at the initial visit versus 64.4% at the last clinic visit
      had GHb values above the target level of 7.0%. Using a stepwise multiple
      regression models, age, higher GHb, FPG, follow-up period, and number of follow
      up visits increased and higher systolic BP and female gender significantly
      decreased the percent glycemic change. Conclusions. This study highlights that
      more than 64.4% of the patients have GHb values higher than 7.0% at last clinic
      visit andindicatesthe difficult challenges physicians face when treating their
      patients with type 2 diabetes. Clinical efforts should focus on more effective
      methods for glycemic control in diabetic patients.

PMID- 23119181
TI  - Stanniocalcin-1 co-localizes with insulin in the pancreatic islets.
AB  - The polypeptide hormone stanniocalcin-1 (STC-1) is widely expressed in mammals
      and signals both locally and systemically. In many tissues STC-1 ligand is
      sequestered by target cell organelles (mitochondria, nuclei, and cholesterol
      lipid droplets) to exert diverse biological effects. Most notably, STC-1 serves
      as an uncoupler of oxidative phosphorylation in liver, muscle, and kidney
      mitochondria. The present paper describes the identification of STC-1 receptors
      in mouse pancreatic beta cells and the discovery that the ligand co-localizes
      with insulin in pancreatic beta cells. In situ hybridization (ISH) analysis
      subsequently revealed that pancreatic beta cells were the source of the ligand.
      Intriguingly however, all ISH signal was localized over putative islet cell
      nuclei as opposed to the cell cytoplasm. Real-time qPCR and agarose gel
      electrophoresis revealed that the STC-1 amplicon generated from islet cell total
      RNA was the same size as that from kidney. However, relative levels of STC-1 gene
      expression were >100-fold lower in islets than those in kidney tissue.
      Collectively, these findings are indicative of a local STC-1 signalling pathway
      in pancreatic beta cells. The role of STC-1 in this context remains to be
      established, but it could very well entail the regulation of beta cell
      mitochondria membrane potential which is an integral aspect of regulated insulin
      release. Interestingly, STC-1 immunoreactivity was not evident in embryonic
      pancreatic islets, suggesting that ligand synthesis may only commence
      postnatally.

PMID- 23119183
TI  - Deficits in scaling of gait force and cycle in parkinsonian gait identified by
      long-term monitoring of acceleration with the portable gait rhythmogram.
AB  - To examine the range of gait acceleration and cycle in daily walking of patients
      with Parkinson's disease (PD), we compared the gait of 40 patients with PD and 17
      normal controls by using a newly developed long-term monitoring device that
      extracts gait-related accelerations from overall movements-related accelerations.
      The range of change in gait acceleration, relative to the control, was less than
      75% in 12 patients. The range of change in gait cycle was less than 75% in 8
      patients. The range of changes in both parameters was less than 75% in 4
      patients. The results suggest narrow changes in gait parameters in PD.

PMID- 23119182
TI  - Cardiac manifestations of rheumatological conditions: a narrative review.
AB  - Cardiovascular diseases are common in systemic rheumatologic diseases. They can
      be presented at the time of diagnosis or after diagnosis. The cardiac
      involvements can be the first presentation of rheumatologic conditions. It means
      that a patient with rheumatologic disease may go to a cardiologist when attacked
      by this disease at first. These manifestations are very different and involve
      different structures of the heart, and they can cause mortality and morbidity of
      patients with rheumatologic diseases. Cardiac involvements in these patients vary
      from subclinical to severe manifestations. They may need aggressive
      immunosuppressive therapy. The diagnosis of these conditions is very important
      for choosing the best treatment. Premature atherosclerosis and ischemic heart
      disease are increased in rheumatoid arthritis and systemic lupus erythematosus,
      and may be causes of mortality among them. The aggressive control of systemic
      inflammation in these diseases can reduce the risk of cardiovascular disease
      especially ischemic heart disease. Although aggressive treatment of primary
      rheumatologic diseases can decrease mortality rate and improve them, at this
      time, there are no specific guidelines and recommendations, to include aggressive
      control and prevention of traditional risk factors, for them.

PMID- 23119184
TI  - Insights into the pathogenesis of takotsubo syndrome, which with persuasive
      reasons should be regarded as an acute cardiac sympathetic disease entity.
AB  - The pathogenesis of takotsubo syndrome (TS) has not been established yet. The
      literature data dealing with the pathogenesis of TS are abundant but scattered
      among different medical specialities. Subarachnoid hemorrhage and other acute
      intracranial diseases and injuries are among the important and currently well
      recognized trigger factors for TS. In both induced and spontaneous subarachnoid
      hemorrhages, signs suggestive of increased cardiac sympathetic overactivity have
      been documented. Surgical and pharmacological sympathectomy has shown to have
      protective cardiac effects in both animal and human studies. Increase in local
      release of norepinephrine from the heart of patients with TS has been measured.
      Signs of both cardiac sympathetic denervation and myocardial lesions adjacent to
      the cardiac nerve terminals have been seen. Furthermore, the systematized and
      typically circumferential pattern of ventricular wall motion abnormality is
      incongruent with the coronary artery supply region and appears most likely to
      follow the cardiac sympathetic nerve distribution. In conclusion, compelling
      literature data support the hypothesis that acute cardiac sympathetic disruption
      and norepinephrine seethe and spillover is causing TS in predisposed patients. TS
      is most probably an acute cardiac sympathetic disease entity causing myocardial
      stunning in which takotsubo is one among other cardiac image study findings.

PMID- 23119186
TI  - Dose-painted intensity modulated radiation therapy improves local control for
      locally advanced pancreas cancer.
AB  - Background. To evaluate the outcomes, adverse events, and therapeutic role of
      Dose-Painted Intensity-Modulated Radiation Therapy (DP-IMRT) for locally advanced
      pancreas cancer (LAPC). Methods. Patients with LAPC were treated with induction
      chemotherapy (n = 25) and those without metastasis (n = 20) received DP-IMRT
      consisting of 45 Gy to Planning Treatment Volume 1 (PTV1) including regional
      lymph nodes with a concomitant boost to the PTV2 (gross tumor volume + 0.5 cm) to
      either 50.4 Gy (n = 9) or 54 Gy (n = 11) in 25 fractions. DP-IMRT cases were
      compared to three-dimensional conformal radiation therapy (3D-CRT) plans to
      assess the potential relationship of radiation dose to adverse events. Kaplan
      Meier and Cox regression analyses were used to calculate survival probabilities.
      The Fisher exact test and t-test were utilized to investigate potential
      prognostic factors of toxicity and survival. Results. Median overall and
      progression-free survivals were 11.6 and 5.9 months, respectively. Local control
      was 90%. Post-RT CA-19-9 levels following RT were predictive of survival (P =
      0.02). Grade 2 and >=grade 3 GI toxicity were 60% and 20%, respectively. In
      comparison to 3D-CRT, DP-IMRT plans demonstrated significantly lower V45 values
      of small bowel (P = 0.0002), stomach (P = 0.007), and mean liver doses (P =
      0.001). Conclusions. Dose-escalated DP-IMRT offers improved local control in
      patients treated with induction chemotherapy for LAPC. Radiation-related
      morbidity appears reduced with DP-IMRT compared to 3D-CRT techniques, likely due
      to reduction in RT doses to organs at risk.

PMID- 23119187
TI  - Recurrent giant pilomatrixoma of the face: a case report and review of the
      literature.
AB  - Pilomatrixoma, also known as pilomatricoma, is a benign tumor that originates
      from the matrix of the hair root. It usually presents as a single, slow-growing
      subcutaneous or intradermal firm nodule with a general size of less than 3
      centimeters (cm) in diameter. However, giant pilomatrixomas (more than 5 cm) have
      been reported infrequently. It is more common in females and usually presents
      during the first two decades of life (60%) as an asymptomatic, mobile, hard,
      elastic mass. Most of the cases are benign and affect the face. The authors
      report a rare case of a giant pilomatricoma of the cheek and discuss the surgical
      management of these lesions, histopathological findings, and review of the
      literature.

PMID- 23119188
TI  - Hexa helix: modified quad helix appliance to correct anterior and posterior
      crossbites in mixed dentition.
AB  - Among the commonly encountered dental irregularities which constitute developing
      malocclusion is the crossbite. During primary and mixed dentition phase, the
      crossbite is seen very often and if left untreated during these phases then a
      simple problem may be transformed into a more complex problem. Different
      techniques have been used to correct anterior and posterior crossbites in mixed
      dentition. This case report describes the use of hexa helix, a modified version
      of quad helix for the management of anterior crossbite and bilateral posterior
      crossbite in early mixed dentition. Correction was achieved within 15 weeks with
      no damage to the tooth or the marginal periodontal tissue. The procedure is a
      simple and effective method for treating anterior and bilateral posterior
      crossbites simultaneously.

PMID- 23119189
TI  - Platelet-Rich Fibrin with beta-Tricalcium Phosphate-A Noval Approach for Bone
      Augmentation in Chronic Periapical Lesion: A Case Report.
AB  - Introduction. This paper describes a case of bone augmentation with combination
      of Platelet-Rich Fibrin (PRF) and beta-TCP for treatment of chronic periapical
      cyst. The case was followed for 12 months. Methods. Patient presented with
      chronic periapical lesion in maxillary anterior teeth with history of trauma 8
      years back. Radiographically, a periapical cyst was seen in relation to maxillary
      left central and lateral incisors. Conventional endodontic treatment was started.
      Since it was not successful, apical surgery was performed. Bone augmentation was
      done using PRF in combination with beta-TCP bone graft to achieve faster healing
      of the periapical region. Regular followups at 3, 6, 9, and 12 months were done.
      Results. Healing was uneventful. Follow-up examinations revealed progressive,
      significant, and predictable clinical and radiographic bone regeneration/healing
      without any clinical symptoms. Conclusions. Combined use of PRF and beta-TCP for
      bone augmentation in treatment of periapical defects is a potential treatment
      alternative for faster healing than using these biomaterials alone.

PMID- 23119185
TI  - Oxidative stress and lipid peroxidation products in cancer progression and
      therapy.
AB  - The generation of reactive oxygen species (ROS) and an altered redox status are
      common biochemical aspects in cancer cells. ROS can react with the
      polyunsaturated fatty acids of lipid membranes and induce lipid peroxidation. The
      end products of lipid peroxidation, 4-hydroxynonenal (HNE), have been considered
      to be a second messenger of oxidative stress. Beyond ROS involvement in
      carcinogenesis, increased ROS level can inhibit tumor cell growth. Indeed, in
      tumors in advanced stages, a further increase of oxidative stress, such as that
      occurs when using several anticancer drugs and radiation therapy, can overcome
      the antioxidant defenses of cancer cells and drive them to apoptosis. High
      concentrations of HNE can also induce apoptosis in cancer cells. However, some
      cells escape the apoptosis induced by chemical or radiation therapy through the
      adaptation to intrinsic oxidative stress which confers drug resistance. This
      paper is focused on recent advances in the studies of the relation between
      oxidative stress, lipid peroxidation products, and cancer progression with
      particular attention to the pro-oxidant anticancer agents and the drug-resistant
      mechanisms, which could be modulated to obtain a better response to cancer
      therapy.

PMID- 23119190
TI  - Coexistence of Multiple Endocrine Neoplasia Type 2B and Chilaiditi Sign: A Case
      Report.
AB  - We present a 15-year-old female patient with medullary thyroid carcinoma,
      marfanoid habitus, and mucosal ganglioneuromatosis. Our case had a RET
      protooncogene mutation ser836 polymorphism in exon 14 and ser904 polymorphism in
      exon 15. Our patient is thought to be atypical MEN2B due to the absence of M918T
      or A883F mutations. Chilaiditi sign is an incidental radiographic finding of a
      usually asymptomatic condition in which a part of intestine is located between
      the liver and diaphragm; however, the term "Chilaiditi syndrome" is used for
      symptomatic hepatodiaphragmatic interposition. The patient had no symptoms as
      abdominal pain, constipation, diarrhea, or emesis. Incidentally, Chilaiditi sign
      was diagnosed with chest radiograph and thoracoabdominal CT. Our case is the
      first in the literature indicating the coexistence of Chilaiditi sign and MEN2B.

PMID- 23119191
TI  - 2 Cases of Bullosis Diabeticorum following Long-Distance Journeys by Road: A
      Report of 2 Cases.
AB  - Background. Bullosis diabeticorum is a distinct, spontaneous, noninflammatory,
      and blistering condition of acral skin that is unique to diabetics. It is rare.
      Exact aetiopathogenesis is not known, but many attributed peripheral neuropathy
      as a potent risk factor, others hypothesized the role of trauma, UV light, and
      nephropathy. Aim. To present cases of bullosis diabeticorum following long
      distance journeys by road. Methods. History and physical examinations were done
      on 2 diabetics who presented with bilateral feet bullae following a long journey.
      Biopsy of a circumferential area of the bullae including adjoining apparently
      normal skin was done. Results. Features of peripheral neuropathy were noted. One
      developed digital gangrene without features of peripheral vascular disease.
      Culture of aspirate from a bullae yielded Staphylococcus aureus. Tissue biopsy
      showed hyperkeratotic focally acanthotic pigmented epidermis with subcorneal
      separation of the granular layer of the epidermis by aggregates of viable and
      nonviable polymorphs and lymphocytes. There is mild acantholysis of the
      epidermis, and a fibrocollagenous dermis which is moderately infiltrated by
      lymphocytes. Conclusion. Long journeys by road is a strong factor in the
      aetiopathogenesis of bullosis diabeticorum on a background of peripheral
      neuropathy. Diabetics especially those with peripheral neuropathy should be
      cautious while traveling long journeys by road.

PMID- 23119192
TI  - Levothyroxine and prednisone causing generalized weakness in a middle-aged man.
AB  - Thyrotoxic induced hypokalemic periodic paralysis is a rare disorder that had
      been described in middle-aged men, predominantly Asians and Hispanics. This case
      presented with generalized weakness and hypokalemia after changing prescription
      for levothyroxine and starting prednisone to treat upper respiratory infection in
      a previously asymptomatic middle-aged Hispanic male. In this paper, we will go
      over the clinical presentation, mechanisms, and treatment of thyrotoxic induced
      hypokalemic periodic paralysis. Our objectives are to identify the classic
      constellation of findings in thyrotoxic periodic paralysis and to recognize the
      importance of considering thyrotoxic periodic paralysis among patients with
      hypokalemia.

PMID- 23119193
TI  - Two cases of diffuse duodenitis associated with ulcerative colitis.
AB  - The upper gastrointestinal tract is not generally considered a target organ in
      ulcerative colitis (UC). However, several cases showing upper gastrointestinal
      involvement in UC have been reported. In this report, we present 2 rare cases of
      diffuse duodenitis accompanying pancolonic UC. Case patient 1 was a 44-year-old
      man who developed diffuse duodenitis shortly after colectomy and was successfully
      treated with mesalazine. Case patient 2 was a 25-year-old woman who developed
      diffuse duodenitis under a steroid-free condition and was successfully treated
      with prednisolone. The 2 patients had Helicobacter pylori-negative duodenitis
      that resembled colonic lesions of UC in both the endoscopic and histological
      findings. No evidence of Crohn's disease was found in these cases. We diagnosed
      both cases as typical UC-associated diffuse duodenitis. The occurrence of
      gastrointestinal involvement in UC has been attracting attention because such
      lesions could potentially open a new window for studying the etiology and
      pathogenesis of UC. Further studies involving a large number of patients are
      needed to clarify whether the upper gastrointestinal tract is a target organ in
      UC.

PMID- 23119194
TI  - Typhoidal tularemia: 2 familial cases.
AB  - Eastern France was not known as a region endemic for tularemia until year 2006.
      We report on 2 cases of typhoidal tularemia in Eastern France, a 43-year-old
      hospitalized woman and her husband. Diagnosis was established after fever
      clearance on serodiagnosis criteria. The source of infection is unclear. As
      persons in the same family may likely be exposed to a common zoonotic source of
      infection, tularemia should be considered in the etiologies of familial fever
      epidemics.

PMID- 23119195
TI  - Microbiology and Management of Pediatric Liver Abscesses: Two Cases Caused by
      Streptococcus anginosus Group.
AB  - Pyogenic liver abscesses in the pediatric population are rare occurrences in the
      developed world. We present two cases of previously healthy males presenting with
      fever and abdominal pain found to have liver abscesses due to organisms in the
      Streptococcus anginosus group. The microbiology of S. anginosus along with the
      management and recommended treatment in children with liver abscesses is
      discussed.

PMID- 23119196
TI  - Endoscopic extracapsular removal of pituitary adenoma: the importance of
      pretreatment of an adjacent unruptured internal carotid artery aneurysm.
AB  - The presence of an intracranial aneurysm together with a pituitary adenoma
      presents tremendous risk of subarachnoid hemorrhage, during transsphenoidal
      surgery, particularly when the aneurysm lies near the operative field. A left
      supraclinoid internal carotid artery aneurysm and a clinically nonfunctioning
      pituitary adenoma coexisted in a 57-year-old woman. Initially, the aneurysm was
      treated by endovascular coil placement, and then the patient underwent
      pseudocapsule-based extracapsular resection of the pituitary tumor via a
      transnasal transsphenoidal endoscopic approach. Pseudocapsule-based extracapsular
      total resection was safely performed, because of the extirpated risk of rupture
      of the coil-treated aneurysm. Recently, transsphenoidal pseudocapsule-based
      extracapsular resection approach for pituitary adenomas provides a more effective
      and safe alternative compared to the traditional intracapsular one because of its
      higher tumor removal and remission rates and lower recurrence rate. Compared with
      conventional subcapsular removal, pseudocapsule-based extracapsular resection has
      more risks of aneurysmal rupture that is located adjacent to pituitary adenoma.
      Thus, in a patient having a cerebral aneurysm with the proximity to the operative
      field, the cerebral aneurysm should be first treated with endovascular coil
      placement or direct surgical procedure; subsequently, pseudocapsule-based
      extracapsular resection of the pituitary tumor via a transnasal transsphenoidal
      endoscopic approach should be performed.

PMID- 23119197
TI  - Ruptured noncommunicating rudimentary horn pregnancy at 19 weeks with previous
      cesarean delivery: a case report.
AB  - Unicornuate uterus with noncommunicating rudimentary horn occurs due to
      incomplete fusion of mullerian ducts. Pregnancy in this horn is a rare phenomenon
      usually resulting in rupture during second trimester of pregnancy. Prerupture
      diagnosis of pregnancy in rudimentary horn with ultrasonography is technically
      difficult, with sensitivity of 30%. We report a case of ruptured non
      communicating rudimentary horn at 19 weeks in a woman with previous Cesarean
      delivery. She had a routine malformation scan in which diagnosis was missed.
      Later she presented to emergency in shock, with massive hemoperitoneum and
      ruptured horn. So a high index of suspicion is required to save this catastrophic
      event and associated maternal morbidity and mortality. In our opinion, routine
      excision of rudimentary horn should be undertaken during nonpregnant state
      laparoscopically. However, those women who refuse should be adequately counseled
      regarding potential complications and if pregnancy occurs in rudimentary horn,
      first trimester laparoscopic excision should be done.

PMID- 23119198
TI  - Dedifferentiated leiomyosarcoma of the uterus with heterologous elements: a
      potential diagnostic pitfall.
AB  - Dedifferentiation is a phenomenon that is well characterized in a variety of
      tumors and is defined by the occurrence of a high-grade or undifferentiated
      tumor, typically unrecognizable regarding its line of differentiation, from a low
      grade/borderline neoplasm. This phenomenon has previously been described in 2
      uterine leiomyosarcomas, but both were devoid of heterologous elements. The
      authors describe herein a case of a dedifferentiated leiomyosarcoma of the uterus
      with osteoid heterologous elements, believed to be the first such reported case.
      The original tumor was a high-grade leiomyosarcoma with large low-grade and
      leiomyoma-like areas and whose constituent cells displayed intense nuclear
      immunoreactivity for both estrogen receptor (ER) and progesterone receptor (PR)
      in approximately 30% of cells. The tumor recurred six months after its resection
      as an undifferentiated sarcoma that was negative for smooth muscle markers, but
      which remained positive for ER and PR. Osteoid production was only identified in
      the recurrent tumor and was significant in extent therein. This case highlights
      the immunophenotypic changes that may occur in dedifferentiated leiomyosarcomas,
      and this possibility should be a consideration when an apparently
      undifferentiated sarcoma is identified in a patient with a history of uterine
      leiomyosarcoma. In our case, the expression of ER and PR provided significant
      supportive evidence of the uterine origin of the recurrent tumor.

PMID- 23119199
TI  - Extragastrointestinal Stromal Tumor during Pregnacy.
AB  - Extragastrointestinal stromal tumors (EGISTs) are mesenchymal neoplasms without
      connection to the gastrointestinal tract. Gastrointestinal stromal tumors (GISTs)
      and EGIST are similar according to their clinicopathologic and histomorphologic
      features. Both of them most often express immunoreactivity for CD-117, a c-kit
      proto-oncogene protein. The coexistence of GIST and pregnancy is very rare, with
      only two cases reported in the literature. In this paper, we presented the first
      EGIST case during pregnancy in the literature.

PMID- 23119200
TI  - Bladder cancer in an inguinoscrotal vesical hernia.
AB  - We present the case of a 79-year-old male who, due to hematuria, underwent
      cystoscopy that showed a lesion in the bladder dome. Transurethral resection was
      attempted, but access to the tumor by this route was impossible. Given the
      findings, a body CT scan was performed showing an inguinoscrotal hernia with
      vesical carcinoma contained. Open surgical treatment of the vesical carcinoma
      contained within the inguinoscrotal hernia was performed in conjunction with the
      hernia repair. The anatomical pathology report confirmed a high-grade urothelial
      carcinoma (stage pT2b) with a free resection margin of <1 mm. Adjuvant
      radiotherapy was selected for subsequent treatment. The presence of bladder tumor
      in an inguinoscrotal hernia is an uncommon finding and a diagnostic delay can be
      assumed. The initial therapeutic plan may need to be changed from the usual
      approaches due to the atypical presentation.

PMID- 23119201
TI  - Multiple Pigmented Bowen's Disease: A Diagnostic and Therapeutic Dilemma.
AB  - Bowens' disease (BD) is a precancerous condition of skin and/or mucosa with a
      predilection towards sun-exposed areas. Extensive literature research failed to
      reveal any case of multiple pigmented BD in type V Fitzpatrick skin. Multiple BD
      is a therapeutic challenge with a tendency to recur. Here we present an otherwise
      healthy Indian male having multiple pigmented lesions of BD on sun-protected
      sites of the body mimicking malignant melanoma. These lesions were refractory to
      treatment with different modalities. This paper is an attempt to review the
      available literature regarding the pigmented variant of multiple BD. Rationale
      for a therapeutic trial of UVB therapy for multiple arsenic induced BD is also
      discussed.

PMID- 23119202
TI  - A Case of a Metastatic Disease to the Pancreas from a Small-Cell Lung Carcinoma
      Documented by a CT-Scan-Guided Trucut Biopsy: The Diagnostic Role of
      Cytomorphology and Immunohistochemistry.
AB  - Unlike primary pancreatic carcinoma, metastatic lesions of the pancreas are
      uncommon and account for approximately 2% of pancreatic malignancies. Small-cell
      lung carcinoma (SCLC) represents a group of highly malignant tumors giving rise
      to early and widespread metastasis at the time of diagnosis. However, the
      pancreas is a relatively infrequent site of metastasis by this neoplasm, and
      reports on metastatic small-cell carcinoma (SCC) in the pancreas, either of
      pulmonary or extrapulmonary origin, to be diagnosed by CT-scan-guided trucut
      biopsy (CT-TCB) are very rare. A 56-year-old man presented with a laterocervical
      lymphadenopathy associated to a mixed-density lung mass and a mass in the
      pancreatic body. CT-TCB slides from the pancreatic mass contained small, round
      tumor cells with extensive nuclear molding. The cytomorphological and
      histological diagnosis was metastatic SCC. Immunocytochemical staining showed
      that a variable number of neoplastic cells were positive for cytokeratin 7, TTF1,
      chromogranin A, and synaptophysin but negative for leukocyte common antigen and
      cytokeratin 20 with a very high expression of KI67. The transbronchial needle
      biopsy confirmed the diagnosis of an SCC. This case represents a rare metastatic
      lesion in the pancreas from SCLC, diagnosed by CT-TCB histological and
      immunohistochemical studies.

PMID- 23119203
TI  - Primary Small-Cell Carcinoma of the Palate with Cushing's Syndrome: A Case
      Report.
AB  - We report a 24-year-old woman presenting with a relapsed soy-bean-size tender
      mass at the junction of the soft and hard palate and a history of palatine tumor
      of small cell carcinoma. Reexcision surgery was performed and histopathological
      features were consistent. The patient was treated with six cycles of chemotherapy
      consisting of etoposide and cisplatin. After one year, the patient developed bone
      metastases and Cushing's syndrome, and successfully recovered with subsequent
      chemotherapy with irinotecan and cisplatin plus radiotherapy. There was no
      evidence of recurrence or metastasis for more than three years. Small cell
      carcinoma originating in the head and neck region has been reported to be highly
      aggressive and has a poor prognosis. This is the first case report of a patient
      with relapsed primary small cell carcinoma of the palate and successfully treated
      with second-line chemotherapy and local radiotherapy.

PMID- 23119204
TI  - Purely cortical anaplastic ependymoma.
AB  - Ependymomas are glial tumors derived from ependymal cells lining the ventricles
      and the central canal of the spinal cord. It may occur outside the ventricular
      structures, representing the extraventicular form, or without any relationship of
      ventricular system, called ectopic ependymona. Less than fifteen cases of ectopic
      ependymomas were reported and less than five were anaplastic. We report a rare
      case of pure cortical ectopic anaplastic ependymoma.

PMID- 23119205
TI  - Turcot syndrome: a synchronous clinical presentation of glioblastoma multiforme
      and adenocarcinoma of the colon.
AB  - Turcot syndrome (TS) is a rare hereditary disorder clinically characterized by
      the occurrence of primary tumors of the colon and the central nervous system
      (CNS). Here we present the case of an 11-year-old boy with a synchronous clinical
      presentation of both glioblastoma multiforme (GBM) and colonic adenocarcinoma. A
      molecular genetic study revealed microsatellite instability in the DNA mismatch
      repair (MMR) gene. This patient ultimately survived for 13 months after clinical
      presentation. Based on this case study, the synchronous presentation of
      glioblastoma multiforme and adenocarcinoma of the colon might suggest a shorter
      survival rate for patients with Turcot syndrome. A literature review complements
      this paper.

PMID- 23119206
TI  - Nonepiphyseal giant cell tumor of the rib: a case report.
AB  - A case of a 32-year-old female patient with a giant cell tumor originating in the
      middle part of the left 10th rib is presented. On X-rays and CT, the tumor caused
      a well-defined osteolysis with nonsclerotic borders. On MRI, it exhibited
      intermediate signal intensity on T1 sequences and central high signal and
      peripheral intermediate signal on T2 sequences. On contrast-enhanced MR images
      both central and peripheral-periosteal enhancement was noted. Thanks to its small
      size (2 * 1.3 cm), the lesion was easily resected en bloc with a part of the
      affected rib. The patient is free of recurrence for 3 years after the operation.

PMID- 23119207
TI  - Epidural brain metastases in a patient with early onset pancreatic cancer: a case
      report and literature review.
AB  - We present a case of early onset pancreatic cancer related extra-axial brain
      metastases. A 46-year-old Caucasian non-Jewish nonobese male with a history of PC
      diagnosed 3 months ago with metastases to the liver, omentum, malignant ascites,
      and a history of a pulmonary embolism was admitted to the hospital because of a
      new onset headache, nausea, and vomiting which started 2 days prior to the
      encounter. Brain MRI was ordered, which showed acute bihemispheric subdural
      hematomas and left hemispheric extra-axial heterogeneously enhancing lesions
      consisting with metastatic disease. The patient was started on ondansentron,
      metoclopramide, and dexamethasone. The cranial irradiation was started, and the
      patient's headache and nausea significantly improved. There are only 9 published
      reports of extra-axial brain metastases related to the pancreatic cancer, whereas
      our paper is the first such case reported on a patient with epidural metastases
      and early onset pancreatic cancer.

PMID- 23119208
TI  - Bilateral Ischemic Optic Neuropathy Developed under Interferon Therapy.
AB  - Introduction. Interferon is a glycoprotein produced by assigned cells of immune
      system. It has been used in many different diseases. Although flu-like syndrome,
      myalgia, rash, hypotension, thrombocytopenia and peripheral neuropathy due to
      interferon use are encountered frequently, ocular side effects are rare,
      generally mild and transient. Case Report. 47-year-old female patient, presented
      with a mass lesion in right renal pelvis. Right radical nephrectomy was applied
      and the histopathological examination was consistent with papillary renal cell
      carcinoma. Interferon alpha treatment was started subcutaneously at the dose of 5
      MIU/3 times in a week. Four weeks after the interferon therapy, suddenly
      bilateral visual loss developed. We discussed the diagnosis, followup, and
      treatment of the patient who developed irreversible ischemic optic neuropathy and
      had no previous known primary systemic disease to cause this condition.
      Conclusion. We suggest that patients should be screened for risk factors causing
      optic ischemic neuropathy, before interferon therapy. Although there was no
      adequate information in the literature for the followup, patients should be
      monitorized before, 1 month after, and 2 months after the treatment. And if there
      is no complication, we suggest that they should be followed up at 3-month
      intervals.

PMID- 23119209
TI  - Pigmented free-floating posterior vitreous cyst.
AB  - Vitreous cysts are very rare ocular malformations. In this observational case
      study, we report on an unusual case of a pigmented free-floating vitreous cyst
      and discuss its differential diagnosis. A 14-year-old male was referred to
      ophthalmology for a pigmented lesion in his left eye. He complained of an
      intermittent floater in the left eye. Visual acuity was 20/20 in the right eye
      and 20/40 in the left eye. Fundus examination was unremarkable bilaterally,
      except for a piece of brownish oval material floating in the vitreous in the left
      eye. He had received a knock on the left side of his head a few days before the
      visual discomfort of the left eye. Real-time ultrasound of the left eye detected
      a piece of hyperechogenic spherical material with no internal reflectivity,
      floating in the middle of the vitreous. The first use of color Doppler ultrasound
      in this context indicated no arterial flow, ruling out the presence of a
      persistent hyaloid artery. Intraocular cysts are rare ocular disorders, which
      have been divided into clear and pigmented cysts, and into those that occupy the
      anterior chamber, the retrolental space, and the vitreous cavity. This last is
      extremely rare. We describe such a case.

PMID- 23119210
TI  - The Role of KRAS Mutational Analysis to Determine the Site of Origin of
      Metastatic Carcinoma to the Lung: A Case Report.
AB  - Metastatic carcinomas involving the lung are a common specimen encountered in
      surgical pathology. These metastases may have different morphologic, and
      architectural patterns and may mimic primary pulmonary adenocarcinoma, especially
      the intra-alveolar (lepidic) pattern of spread which may simulate a primary
      pulmonary bronchioloalveolar carcinoma (adenocarcinoma in situ). We present the
      case of a metastatic pancreatic adenocarcinoma that morphologically mimicked
      bronchioloalveolar carcinoma of the lung in that the tumor had an exclusive intra
      alveolar pattern of spread and had an immunophenotype that was noninformative as
      to the site of origin (cytokeratin 7+, cytokeratin 20-, TTF-1-). In this case, we
      used KRAS gene mutation analysis to support that the lung carcinoma represented a
      metastatic pancreatic carcinoma as they both possessed identical codon 12 KRAS
      mutations. We show that this method may be a useful way to prove site of origin
      of metastatic carcinoma-particularly if standard morphologic or
      immunohistochemical analysis is not definitive.

PMID- 23119211
TI  - MFH Mimic in Breast: A High-Grade Malignant Phyllodes Tumor.
AB  - Malignant phyllodes tumor is usually diagnosed by the presence of benign duct
      like epithelium and malignant mesenchymal tissue. In addition to the usual
      fibrosarcomatous features, the mesenchymal component may show areas resembling
      osteogenic sarcoma, chondrosarcoma, liposarcoma, leiomyosarcoma,
      rhabdomyosarcoma, malignant mesenchymoma, and, very rarely, malignant fibrous
      histiocytoma. We present one such rare case of malignant phyllodes tumor with
      malignant fibrous histiocytoma-like stromal differentiation.

PMID- 23119212
TI  - A case of male goltz syndrome.
AB  - We present the case of a boy with a clinical diagnosis of Goltz syndrome (focal
      dermal hypoplasia), a rare genodermatosis characterized by widespread dysplasia
      of mesodermal and ectodermal tissues. A 9-year-old male patient with Goltz
      syndrome presented with typical skin lesions along with progressive dimness of
      vision and mental retardation since birth. It is inherited in an X-linked
      dominant fashion and is normally lethal in male patients, and so very few male
      patients, like the index case, have been reported.

PMID- 23119213
TI  - An unusual case of suspected microvascular angina in a newborn.
AB  - Myocardial ischemia in pediatric population is uncommon and usually due to
      congenital heart disease or extracardiac conditions leading to poor coronary
      perfusion. A 6-day-old newborn presented with respiratory distress and signs of
      heart failure. ECG, echocardiography, and laboratory results were consistent with
      myocardial ischemia. Coronary angiography was performed to exclude anomalous
      origin of coronary arteries, showing normal coronary artery origin and course.
      Thrombophilia and extra-cardiac causes were ruled out. Clinical conditions
      improved with mechanical ventilation and diuretics, enzyme levels lowered,
      repolarisation and systolic function abnormalities regressed, but ischemic
      electrocardiographic and echocardiographic signs still presented during intense
      crying. Becaues of suspicion of microvascular angina, therapy with ASA and beta
      blocker was started. At 5 month followup, the baby was in good clinical condition
      and no more episodes were recorded. We believe it is an interesting case, as no
      similar cases have been recorded till now.

PMID- 23119214
TI  - Effectiveness of Electroconvulsive Therapy for Depression and Cotard's Syndrome
      in a Patient with Frontotemporal Lobe Dementia.
AB  - In the field of psychogeriatrics, the differential diagnosis of depression and
      dementia, as well as the treatment of depression and comorbid dementia, is an
      important issue. In this paper, the authors present the case of a 72-year-old
      woman with Cotard's syndrome and frontotemporal dementia (FTD) who was admitted
      to a psychiatric hospital with delusions of negation accompanied by depressive
      symptoms. Pharmacotherapy over a 2-year hospitalization was unsuccessful, and she
      was subsequently transferred to our university hospital. A total of 18 sessions
      of electroconvulsive therapy released her from psychomotor inhibition, appetite
      loss, and Cotard's delusions. The indication for electroconvulsive therapy in
      patients with dementia is discussed.

PMID- 23119215
TI  - Radioiodine accumulation in a giant ovarian cystadenofibroma detected
      incidentally by 131-I whole body scans.
AB  - Ovarian cystadenofibroma is a relatively rare tumor; it is usually asymptomatic
      and is found incidentally. We present the case of a 24-year-old female patient,
      who had undergone total thyroidectomy for thyroid papillary carcinoma, with an
      asymptomatic giant cystadenofibroma, incidentally discovered by diagnostic (131)I
      SPECT/CT WBSs. We summarize the clinical history, imaging data, and
      histopathological study on a rare case of radioiodine accumulation in
      cystadenofibroma, and we discuss the mechanism of uptake of radioiodine in this
      case.

PMID- 23119216
TI  - The First Report of an Intraperitoneal Free-Floating Mass (an Autoamputated
      Ovary) Causing an Acute Abdomen in a Child.
AB  - A free-floating intraperitoneal mass is extremely rare, and almost all originate
      from an ovary. Here, we present the first case with an intraperitoneal free
      floating autoamputated ovary that caused an acute abdomen in a child and also
      review the literature. A 4-year-old girl was admitted with signs and symptoms of
      acute abdomen. At surgery, the patient had no right ovary and the right tube
      ended in a thin band that pressed on the terminal ileum causing partial small
      intestine obstruction and acute abdomen. A calcified mass was found floating in
      the abdomen and was removed. The pathological examination showed necrotic tissue
      debris with calcifications. An autoamputated ovary is thought to result from
      ovarian torsion and is usually detected incidentally. However, it can cause an
      acute abdomen.

PMID- 23119217
TI  - A mucinous cystic neoplasm of the mesocolon showing features of malignancy.
AB  - Mucinous cystic neoplasms are rare tumours of uncertain histogenesis. They arise
      from the ovaries, pancreas, and other intra-abdominal sites but more unusually
      from the mesocolon. They can present with abdominal pain, distension, or a
      palpable mass but are commonly an incidental finding. We describe the case of a
      48-year-old woman who was found to have an incidental left pelvic cyst on
      computed tomography. Subsequent laparoscopic excision and histological analysis
      demonstrated the cyst to be a borderline malignant mucinous tumour arising from
      the mesocolon. Mucinous tumours should be considered in the differential
      diagnosis of all intra-abdominal cysts and treatment should be by surgical
      complete excision.

PMID- 23119218
TI  - Teratoma during Pregnancy with Positive Estrogen and Progesterone Receptors and
      Elevated Ca19-9 Antigen Levels.
AB  - We present a 27-year-old female patient admitted with an anterior mediastinal
      mass. She complained of chest discomfort and hemoptysis which began seven months
      prior. She had given birth five months prior. Thoracic X-ray showed an anterior
      mediastinal mass. Thorax computed tomography (CT) confirmed a well-defined
      anterior mediastinal mass with 13 * 12 cm diameter, extending to the right
      hemithorax. It was composed of cystic spaces and discrete areas like soft tissue
      and fat. Serum Ca 19-9 level was elevated. CT features were consistent with a
      mature teratoma. During median sternotomy, the tumor revealed adhesions to the
      right lung and the right subclavian artery. Histologically, the tumor was
      diagnosed as a mature teratoma. Estrogen and progesterone receptors were detected
      to be positive in the resected tissue. We conclude that alterations in hormone
      levels during pregnancy might be the cause of rapid tumor growth which leads to
      hemoptysis.

PMID- 23119219
TI  - Synchronous penile metastasis from a high-grade adenocarcinoma of the prostate.
AB  - Metastasis to the glans penis is a rare phenomenon and usually occurs in a late
      stage of disease. A 68-year-old man was referred to our clinic because of two
      indurated lesions of the glans penis and minor lower urinary tract symptoms.
      Digital rectal examination revealed a hard nodular prostate, and serum prostate
      specific antigen (sPSA) level was 13.3 ng/mL. Biopsies of the penile lesions and
      transrectal ultrasound-guided prostate biopsies were taken. Immunohistochemical
      staining of formalin-fixed paraffin-embedded tissue exposed a synchronous penile
      metastasis from a high-grade adenocarcinoma of the prostate. Except a
      pathologically enlarged lymph node detected with MRI there was no suspicion on
      other metastases. Currently this patient is being treated with a Gonadoreline
      (GnRH) antagonist. Nevertheless, the prognosis will be poor.

PMID- 23119220
TI  - Osseous metaplasia and bone marrow elements in a case of renal cell carcinoma.
AB  - Renal cell carcinoma with osseous metaplasia and bone marrow elements is a
      relatively rare event in these tumors. We discuss pathological differential
      diagnosis for this tumor with a review of the literature on this unusual case.

PMID- 23119221
TI  - Treatment of infected pseudoaneurysm of femoral artery after vascular closure
      device deployment: a practical solution.
AB  - Like other invasive procedures, percutaneous coronary interventions are
      associated with complications. Most common access site for these procedures is
      common femoral artery. Complications such as groin and retroperitoneal hematoma
      can be encountered as well as pseudoaneurysms, arteriovenous fistulas, acute
      arterial occlusion, and infection. When infected pseudoaneurysm occurs, surgical
      treatment can be extremely difficult. We present a case of the patient in whom
      infected pseudoaneurysm of common femoral artery developed after percutaneous
      coronary intervention and was successfully treated by surgical excision and
      autoarterial graft insertion.

PMID- 23119222
TI  - Left atrial appendage exclusion for stroke prevention in atrial fibrillation.
AB  - The public health burden of atrial fibrillation (AF) and associated
      thromboembolic stroke continues to grow at alarming rates. AF leads to a fivefold
      increase in the risk of stroke. Therefore, stroke prevention remains the most
      critical aspect of AF management. Current standard of care focuses on oral
      systemic anticoagulation, most commonly with warfarin and now with newer agents
      such as dabigatran, rivaroxaban, and apixaban. However, the challenges and
      limitations of oral anticoagulation have been well documented. Given the critical
      role of the left atrial appendage (LAA) in the genesis of AF-related
      thromboembolism, recent efforts have targeted removal or occlusion of the LAA as
      an alternative strategy for stroke prevention, particularly in patients deemed
      unsuitable for oral anticoagulation. This paper highlights recent advances in
      mechanical exclusion of the LAA. The problem of AF and stroke is briefly
      summarized, followed by an explanation for the rationale behind LAA exclusion for
      stroke prevention. After briefly reviewing the history of LAA exclusion, we
      highlight the most promising LAA exclusion devices currently available. Finally,
      we discuss future challenges and opportunities in this growing field.

PMID- 23119223
TI  - A warning index used in prescreening for Alzheimer's disease, based on self
      reported cognitive deficits and vascular risk factors for dementia in elderly
      patients with type 2 diabetes.
AB  - Background/Aims. Diabetes might increase the risk of Alzheimer's disease (AD).
      For detecting dementia, it is typical to obtain informants' perceptions of
      cognitive deficits, but such interviews are usually difficult in routine care. We
      aimed to develop a model for predicting mild to moderate AD using a self-reported
      questionnaire and by evaluating vascular risk factors for dementia in elderly
      subjects with diabetes. Methods. We recruited 286 diabetic and 155 nondiabetic
      elderly subjects. There were 25 patients with AD and 261 cognitively normal
      individuals versus 30 with AD and 125 normal subjects, respectively. Each
      participant answered subjective questions on memory deficits and daily
      functioning. Information on vascular risk factors was obtained from clinical
      charts, and multivariate logistic regression was used to develop a model for
      predicting AD. Results. The predicted probabilities used in screening for AD in
      diabetic subjects constituted age, education, lower diastolic blood pressure,
      subjective complaints of memory dysfunction noticeable by others, and impaired
      medication, shopping, and travel outside a familiar locality. Receiver operating
      characteristic analysis revealed a satisfactory discrimination for AD specific
      for diabetic elderly subjects, with 95.2% sensitivity and 90.6% specificity.
      Conclusion. This is the first useful index that can prescreen for AD in elderly
      subjects with diabetes.

PMID- 23119224
TI  - Cognitive profiles in Parkinson's disease and their relation to dementia: a data
      driven approach.
AB  - Parkinson's disease is characterized by a substantial cognitive heterogeneity,
      which is apparent in different profiles and levels of severity. To date, a
      distinct clinical profile for patients with a potential risk of developing
      dementia still has to be identified. We introduce a data-driven approach to
      detect different cognitive profiles and stages. Comprehensive neuropsychological
      data sets from a cohort of 121 Parkinson's disease patients with and without
      dementia were explored by a factor analysis to characterize different cognitive
      domains. Based on the factor scores that represent individual performance in each
      domain, hierarchical cluster analyses determined whether subgroups of Parkinson's
      disease patients show varying cognitive profiles. A six-factor solution
      accounting for 65.2% of total variance fitted best to our data and revealed high
      internal consistencies (Cronbach's alpha coefficients >0.6). The cluster analyses
      suggested two independent patient clusters with different cognitive profiles.
      They differed only in severity of cognitive impairment and self-reported
      limitation of activities of daily living function but not in motor performance,
      disease duration, or dopaminergic medication. Based on a data-driven approach,
      divers cognitive profiles were identified, which separated early and more
      advanced stages of cognitive impairment in Parkinson's disease without dementia.
      Importantly, these profiles were independent of motor progression.

PMID- 23119225
TI  - Sex and speciation: Drosophila reproductive tract proteins- twenty five years
      later.
AB  - The protein electrophoresis revolution, nearly fifty years ago, provided the
      first glimpse into the nature of molecular genetic variation within and between
      species and showed that the amount of genetic differences between newly arisen
      species was minimal. Twenty years later, 2D electrophoresis showed that, in
      contrast to general gene-enzyme variation, reproductive tract proteins were less
      polymorphic within species but highly diverged between species. The 2D results
      were interesting and revolutionary, but somewhat uninterpretable because, at the
      time, rapid evolution and selective sweeps were not yet part of the common
      vocabulary of evolutionary biologists. Since then, genomic studies of sex and
      reproduction-related (SRR) genes have grown rapidly into a large area of research
      in evolutionary biology and are shedding light on a number of phenomena. Here we
      review some of the major and current fields of research that have greatly
      contributed to our understanding of the evolutionary dynamics and importance of
      SRR genes and genetic systems in understanding reproductive biology and
      speciation.

PMID- 23119226
TI  - Benefits of hypoxic culture on bone marrow multipotent stromal cells.
AB  - Cultivation of cells is usually performed under atmospheric oxygen tension;
      however, such a condition does not replicate the hypoxic conditions of normal
      physiological or pathological status in the body. Recently, the effects of
      hypoxia on bone marrow multipotent stromal cells (MSCs) have been investigated.
      In a long-term culture, hypoxia can inhibit senescence, increase the
      proliferation rate and enhance differentiation potential along the different
      mesenchymal lineages. Hypoxia also modulates the paracrine effects of MSCs,
      causing upregulation of various secretable factors, including the vascular
      endothelial growth factor and interleukin-6, and thereby promoting wound healing
      and diabetic fracture healing. Finally, hypoxia plays an important role in
      mobilization and homing of MSCs, primarily by its ability to induce stromal cell
      derived factor-1 expression along with its receptor, CXCR4. After
      transplantation, an ischemic environment, that is the combination of hypoxia and
      lack of nutrition, can lead to apoptosis or cell death, which can be overcome by
      the hypoxic preconditioning of MSCs and overexpression of prosurvival genes like
      Akt, HO-1 and Hsp70. This review emphasizes that hypoxia is an important factor
      in all major aspects of stem cell biology, and the mechanism involved in the
      hypoxic inducible factor-1signaling pathway behind these responses is also
      discussed.

PMID- 23119227
TI  - Unbalanced replication as a major source of genetic instability in cancer cells.
AB  - The origin of genetic instability in tumors is a matter of debate: while the
      prevailing model postulates a mutator phenotype resulting from an alteration in a
      caretaker gene as a prerequisite for genetic alterations leading to tumor
      formation, there is evidence against this model in the majority of cancers. A
      model for chromosomal instability should take into account the role of oncogenes
      in directly stimulating DNA and cellular component replication, creating aberrant
      structures when overexpressed. I will distinguish here two distinct mechanisms
      for the genetic instability of tumors: primary and secondary. Primary genetic
      instability is dependent on the inactivation of genes involved in maintaining
      genetic stability (caretaker genes), whereas secondary genetic instability is
      dependent on genes involved in tumor progression, i.e. oncogenes and tumor
      suppressor genes of the gatekeeper type. Secondary genetic instability, the most
      frequent condition, can be explained by the fact that some of the genes involved
      in tumor progression control replication of cell structures from within, leading
      to replication unbalance.

PMID- 23119229
TI  - Phosphorylation of p47phox is required for receptor-mediated NADPH oxidase/NOX2
      activation in Epstein-Barr virus-transformed human B lymphocytes.
AB  - The phagocyte NADPH oxidase (NOX2) is known to be expressed in Epstein-Barr virus
      (EBV)-transformed human B lymphocytes. Phosphorylation of the NOX2 cytosolic
      subunit p47phox is required for phorbol myristate acetate (PMA)-induced NOX2
      activation in EBV-transformed B lymphocytes, however the role of this process in
      receptor-mediated NOX2 activation is not known. Here, we used pansorbin which
      acts by cross linking cell surface IgG and transfected cells with mutated p47phox
      to address if the phosphorylation of this subunit is required for receptor
      mediated NOX2 activation. We show that pansorbin induced NOX2 activation in a
      time and concentration-dependent manner, albeit at levels only of 20% of those
      induced by PMA. GF109203X, a PKC selective inhibitor, inhibited pansorbin as well
      as PMA-induced NOX2 activation. Using specific anti-phospho serine antibodies we
      showed that pansorbin induced p47phox phosphorylation on Ser304, 315, 320, 328,
      and 345 and kinetics of these phosphorylations preceed NOX2 activation. To
      determine whether the phosphorylation of p47phox is required for pansorbin
      induced NOX2 activation, we transfected EBV-transformed lymphocytes deficent in
      p47phox with a plasmid expressing wild type p47phox or p47phox with all the
      phosphorylated serines mutated to alanines, p47phoxS(303-379)A. Results show that
      pansorbin-induced NOX2 activation was greatly decreased in lymphocytes expressing
      the mutant as compared to the wild-type p47phox. These results show that
      pansorbin induced p47phox phosphorylation on multiple sites in EBV-transformed B
      lymphocytes and this process is required for pansorbin-induced NADPH oxidase
      activation in these cells.

PMID- 23119228
TI  - Emerging therapeutic options for myelofibrosis: a Canadian perspective.
AB  - Myelofibrosis (MF) is a clonal stem cell disorder characterized by cytopenias,
      splenomegaly, marrow fibrosis, and systemic symptoms due to elevated inflammatory
      cytokines. MF is associated with decreased survival. The quality of life of
      patients with MF is similar to other advanced malignancies. Allogeneic
      hematopoietic cell transplantation is a curative treatment, but is applicable to
      a minority of patients with MF. None of the conventional therapies are known to
      alter the natural history of the disease. Significant progress has been made in
      the last few years in the understanding of disease biology of MF. Discovery of
      the JAK2V617F mutation paved the way for drug discovery in MF, and the first
      JAK1/2 inhibitor, ruxolitinib, has been approved by FDA and Health Canada.
      Several other JAK1/2 inhibitors are at various stages of clinical development. As
      a consequence, the therapeutic landscape of MF is changing from a disease where
      no effective therapies existed to one with several novel treatment options on the
      horizon. In this report, we assess the changing therapeutic options for MF, and
      critically analyze the position of novel treatments in the current armamentarium.

PMID- 23119230
TI  - Gastrointestinal malignant lymphoma: a pathologic study of 37 cases in a single
      Japanese institution.
AB  - The author reviewed pathologic features of 37 cases of malignant lymphoma in the
      gastrointestinal organs in the last 10 years in our pathology laboratory. The
      current WHO classification was adopted. The 37 cases consisted of 20 males and 17
      female, and the age ranged from 46 to 89 years with a median of 69 years. Of the
      37 cases, 25 cases (68%) were gastric lymphomas, 6 cases (16%) were small
      intestinal lymphomas, and 6 cases (16%) were colon lymphomas. Of the 37 cases, 35
      cases (95%) were B-cell neoplasms and 2 cases (5%) were T-cell neoplasms. In the
      25 gastric lymphomas (male:female=14:11, age range 46-84 years, median 70 years)
      11 cases were diffuse large B-cell lymphomas, and 14 cases were extranodal
      marginal zone B-cell lymphomas (MALT lymphomas). The clinical endoscopic
      diagnosis was gastritis in 3, gastric ulcer in 3, gastric carcinoma in 7,
      carcinoid in 1, submucosal tumor in 1, malignant lymphoma in 2, and suspected
      MALT lymphoma in 8. In the 6 small intestinal lymphomas (male:female=2:4, age
      range 49-89 years, median 70 years), all cases were located in the ileum. Of the
      6 cases, 4 were diffuse large B-cell lymphoma and 2 were peripheral T-cell
      lymphoma. One case showed multiple lymphomas, and one case was associated with
      rectal adenocarcinoma and one case with gastric MALT lymphoma. The clinical
      diagnosis was adenocarcinoma in 2, suspected lymphoma in 2, and ileal tumor in 2.
      In the 6 colon lymphomas (male:female=4:2, age range 69-86 years, median 74
      years), 5 cases were diffuse large B-cell lymphomas and one case was follicular
      lymphoma. Clinical endoscopic diagnosis was GIST in 1, colon carcinoma in 4, and
      colon polyp in 1. Cases of Hodgkin's disease, mantle cell lymphoma, Burkitt
      lymphoma were not recognized in the present series. In summary, the author
      reported pathologic features of 37 cases of gastrointestinal malignant lymphoma
      in our laboratory in the last 10 years.

PMID- 23119231
TI  - Chances of finding a matched parent-child in hematopoietic stem cell
      transplantation in Saudi Arabia.

PMID- 23119232
TI  - Exploring delivery of nutraceuticals using nanotechnology.

PMID- 23119233
TI  - Stimuli sensitive hydrogels for ophthalmic drug delivery: A review.
AB  - Amongst the various routes of drug delivery, the field of ocular drug delivery is
      one of the most interesting and challenging endeavors facing the pharmaceutical
      scientist for past 10-20 years. As an isolated organ, eye is very difficult to
      study from a drug delivery point of view. Despite this limitation, improvements
      have been made with the objective of maintaining the drug in the biophase for an
      extended period. A major problem in ocular therapeutics is the attainment of an
      optimal drug concentration at the site of action. To achieve effective ophthalmic
      therapy, an adequate amount of active ingredient must be delivered and maintained
      within the eye. The most frequently used dosage forms, i.e., eye solution, eye
      ointments, eye gels, and eye suspensions are compromised in their effectiveness
      by several limitations leading to poor ocular bioavailability. Ophthalmic use of
      viscosity-enhancing agents, penetration enhancers, cyclodextrins, prodrug
      approaches, and ocular inserts, and the ready existing drug carrier systems along
      with their application to ophthalmic drug delivery are common to improve ocular
      bioavailability. Amongst these hydrogel (stimuli sensitive) systems are
      important, which undergo reversible volume and/or sol-gel phase transitions in
      response to physiological (temperature, pH and present of ions in organism
      fluids, enzyme substrate) or other external (electric current, light) stimuli.
      They help to increase in precorneal residence time of drug to a sufficient extent
      that an ocularly delivered drug can exhibit its maximum biological action. The
      concept of this innovative ophthalmic delivery approach is to decrease the
      systemic side effects and to create a more pronounced effect with lower doses of
      the drug. The present article describes the advantages and use stimuli sensitive
      of hydrogel systems in ophthalmic drug delivery.

PMID- 23119234
TI  - Isolation and characterization of jackfruit mucilage and its comparative
      evaluation as a mucoadhesive and controlled release component in buccal tablets.
AB  - BACKGROUND: The purpose of the present research work was to extract jackfruit
      mucilage, use it as a mucoadhesive agent, and to develop extended release
      buccoadhesive tablets with an intention to avoid hepatic first-pass metabolism,
      by enhancing residence time in the buccal cavity. MATERIALS AND METHODS: The
      mucilage was isolated from the jackfruit pulp by the aqueous extraction method
      and characterized for various physiochemical parameters as well as for its
      adhesive properties. Three batches of tablets were prepared (wet granulation
      method) and evaluated containing three mucoadhesive components: Methocel K4M,
      Carbopol 974P, and isolated jackfruit mucilage using chlorpheniramine maleate
      (CPM) as a model drug and changing the proportion of the mucoadhesive component
      (1:2:3), resulting in nine different formulations. RESULTS: The results of the
      study indicate that the isolated mucilage had good physicochemical and
      morphological characteristics, granules and tablets conformed to the
      Pharmacopoeial specifications, and in vitro release studies showed the sustained
      action of drug with increasing concentration of the isolated natural mucoadhesive
      agent in the formulations. Permeability studies indicated that changing the
      mucoadhesive component, permeability behavior was not statistically different (P
      > 0.05). FTIR and UV spectroscopy studies between mucilage and CPM suggested the
      absence of a chemical interaction between CPM and jackfruit mucilage. CONCLUSION:
      The developed mucoadhesive tablets for buccal administration containing natural
      mucilage (MF3) have a potential for the sustained action of drug release. Thus,
      mucoadhesive tablets for controlled release were successfully developed using
      natural jackfruit mucilage.

PMID- 23119235
TI  - Ocular insert for sustained delivery of gatifloxacin sesquihydrate: Preparation
      and evaluations.
AB  - BACKGROUND: Many polymeric systems have been used to fabricate ocular inserts for
      improve ocular bioavailability and retention to drug of which matrix systems have
      shown advantages of reduce dosing frequency and increased corneal residence time.
      The objective of the present investigation was to prepare and evaluate ocular
      inserts of gatifloxacin. MATERIALS AND METHODS: Ocular insert was made from an
      aqueous dispersion of gatifloxacin, sodium alginate, polyvinyl alcohol, and
      glycerin by solvent casting method. Ocular insert (5.5 mm) was cross-linked by
      CaCl(2) and was coated with Eudragit RL-100 or Eudragit RS-100. The ocular
      inserts were characterized for thickness; uniformity of weight, drug content
      uniformity, % moisture absorption or moisture loss, and surface pH. The in vitro
      diffusion studies were carried out by putting insert on Millipore membrane filter
      (0.8 MUm) fixed between donor and receptor compartment of an all glass modified
      Franz diffusion cell. RESULTS: The thickness and drug content of ocular insert
      were found in the range of 0.11 +/- 0.003 to 0.24 +/- 0.010 mm and 0.718 +/-
      0.002 to 0.867 +/- 0.007 mg, respectively. The surface pH, % moisture absorption
      or moisture loss and weight variation values were obtained in satisfactory range.
      The cross-linked ocular insert coated with Eudragit RL-100 shows maximum drug
      permeation i.e. 89.53 % +/- 0.43 at 11 h. The stability studies suggest that all
      ocular insert remained stable, showed lesser degradation rate and maximum shelf
      life. CONCLUSION: Ocular inserts of gatifloxacin were prepared successfully by
      using solvent casting method for sustained drug delivery. The cross-linked and
      Eudragit RL-100 coated ocular insert of gatifloxacin provides better in vitro
      drug release and sustained upto 11 h.

PMID- 23119236
TI  - Formulation and evaluation of an in situ gel-forming ophthalmic formulation of
      moxifloxacin hydrochloride.
AB  - BACKGROUND/AIM: The aim of the present investigation is to prepare and evaluate
      in situ gel-forming ophthalmic drug delivery system of moxifloxacin
      hydrochloride. MATERIALS AND METHODS: Sodium alginate, a novel ophthalmic gel
      forming mucoadhesive polymer, which gets converted to gel in the presence of
      divalent-cations (calcium ion) present in the lachrymal fluid, was used as the
      gelling agent. Hydroxy propyl methyl cellulose (HPMC) is a mucoadhesive polymer
      used as viscosity enhancer. Suitable concentrations of buffering agents were used
      to adjust the pH to 6.5. All the formulations were sterilized in an autoclave at
      121 degrees C for 15 minutes. The formulations were evaluated for clarity, pH
      measurement, gelling capacity, drug content estimation, rheological study, in
      vitro diffusion study, antibacterial activity, isotonicity, and eye irritation
      study. RESULTS: The developed formulations exhibited sustained release of drug
      from formulation over a period of 10 hours thus increasing residence time of the
      drug. The optimized formulations were tested for eye irritation on albino rabbit
      (male). The formulations were found to be non-irritating with no ocular damage or
      abnormal clinical signs to the cornea, iris or conjunctiva observed. CONCLUSION:
      These in situ gelling systems containing gums may be a valuable alternative to
      the conventional systems.

PMID- 23119237
TI  - Formulation and evaluation of floating matrix tablet of stavudine.
AB  - BACKGROUND/AIM: The purpose of the study was to prolong the gastric residence
      time of stavudine by designing its floating tablets and to study the influence of
      different polymers on its release rate. MATERIALS AND METHODS: The floating mix
      matrix tablets of stavudine were prepared by melt granulation method. Beeswax was
      used as hydrophobic meltable material. Hydroxypropyl methylcellulose (HPMC),
      sodium bicarbonate, and ethyl cellulose were used as matrixing agent, gas
      generating agent, and floating enhancer, respectively. The prepared tablets were
      evaluated for physicochemical parameters such as hardness, weight variation,
      friability, floating properties (floating lag time, total floating time), drug
      content, stability study, and in vitro drug release. The drug- polymer
      interaction was studied by Differential Scanning Calorimetry (DSC) thermal
      analysis and Fourier transform infared (FT-IR). RESULTS: The floating lag time of
      all the formulations was within the prescribed limit (<3 min). All the
      formulations showed good matrix integrity and retarded the release of drug for 12
      h except the formulation F5.The concentration of beeswax (X(1)), HPMC K(4)M
      (X(2)), and ethyl cellulose (X(3)) were selected as independent variables and
      drug release values at 1 (Q(1)), at 6 (Q(6)) and at 12 h (Q(12)) as dependent
      variables. Formulation F7 was selected as an optimum formulation as it showed
      more similarity in dissolution profile with theoretical profile (similarity
      factor, f(2) = 70.91). The dissolution of batch F7 can be described by zero-order
      kinetics (R(2) =0.9936) with anomalous (non-Fickian) diffusion as the release
      mechanism (n=0.545). There was no difference observed in release profile after
      temperature sensitivity study at 40 degrees C/75% relative humidity (RH) for 1
      month. CONCLUSION: It can be concluded from this study that the combined mix
      matrix system containing hydrophobic and hydrophilic polymer minimized the burst
      release of drug from the tablet and achieved a drug release by zero-order
      kinetics, which is practically difficult with only hydrophilic matrix.

PMID- 23119238
TI  - Solid-state characterization of lacidipine/PVP K(29/32) solid dispersion primed
      by solvent co-evaporation.
AB  - BACKGROUND: Lacidipine (LCDP) is a 1,4-dihydropyridine derivative categorized as
      an anti-hypertensive Ca2+ channel blocker having very low solubility, and thus
      very low oral bioavailability, which presents a challenge to the formulation
      scientists. Homogeneous distribution of poorly water-soluble drugs like LCDP in
      polyvinylpyrrolidone (PVP), a hydrophilic carrier, is definitely a suitable way
      to improve the bioavailability of such drugs. MATERIALS AND METHODS: The aim of
      the study was to develop a combined thermal, imaging, and spectroscopic approach,
      and characterize physical state, dissolution behavior, and elucidation of drug
      PVP interaction in LCDP/PVP solid dispersion (SD) using differential scanning
      calorimetry (DSC), X-ray diffractometry (XRD), fourier transform infrared (FTIR)
      spectroscopy, and hot stage microscopy (HSM), which is the prerequisite for the
      development of a useful drug product. RESULTS: Dissolution studies of LCDP and
      its physical mixture with PVP showed less than 50% release even after 60 min,
      whereas SD of LCDP/PVP ratio of 1:10% w/w showed complete dissolution within 45
      min. DSC and powder XRD proved the absence of crystallinity in LCDP/PVP SD at a
      ratio of 1:10% w/w. The FTIR spectroscopy indicated formation of hydrogen bond
      between LCDP and PVP. In the SD FTIR spectra, the -NH stretching vibrations and
      the -C=O stretch in esteric groups of LCDP shift to free -NH and C=O regions,
      indicating the rupture of intermolecular hydrogen bond in the crystalline
      structure of LCDP. CONCLUSION: Solid-state characterization by HSM, DSC, XRD, and
      FTIR studies, in comparison with corresponding physical mixtures, revealed the
      changes in solid state during the formation of dispersion and justified the
      formation of high-energy amorphous phase.

PMID- 23119239
TI  - Discovery of nasal speculum.

PMID- 23119240
TI  - Rhinosporidiosis.

PMID- 23119241
TI  - Clinical, radiological and surgical correlation in cancers of the paranasal
      sinuses.
AB  - Clinical, radiological and CT findings for each adjacent subsite were tabulated
      and compared in 25 consecutive cases undergoing surgery for malignant lesions of
      the maxillo-ethmoid complex. It was found that tumour extensions into nose,
      palate, cheek and orbit were identified correctly in a high proportion of cases
      clinically and radiologically. Posterior extensions into infratemporal or
      pterygopalatine fossae were evident clinically in only one out of 5 cases.
      Clinical assessment failed to detect orbital invasion in 3 out of 7 cases, while
      CT missed orbital periosteal involvement in one case. CT overestimated spheno
      ethmoidal extensions of tumour in 44% (8/18) cases.

PMID- 23119242
TI  - External septo-rhinoplasty- our experience.
AB  - Septo-Rhinoplasty is a fascinating surgical procedure to both the surgeon and the
      patient. Both hope to obtain good results. Consciousness of the nasal profile
      along with the function led the Rhinologists to adopt various techniques to give
      better access to the nasal bone and cartilages. External Septo-Rhinoplasty gives
      excellent approach to the intranasal and nasal structures. The authors describe
      their experience with external Septo-Rhinoplasty.

PMID- 23119243
TI  - Bacteriological study of chronic maxillary sinusitis.

PMID- 23119244
TI  - Primary tuberculosis of maxilla.

PMID- 23119245
TI  - Inverted papilloma of nose and paranasal sinuses -a clinical study.
AB  - This study includes details of twentytwo cases of inverted papilloma. It is an
      uncommon nasal disease. It is treated more radically than other benign conditions
      of the nasal cavity. The recurrence is frequent and malignant changes are also
      not uncommon. Histopathological study is important and requires opinion from an
      experienced pathologist. Rare extension into ear is also observed though the
      exact mechanism of spread is not understood. Long followup is essential in
      dealing with recurrences.

PMID- 23119246
TI  - Nasal polyps - histopathologic spectrum.
AB  - Analysis of 345 polypoidal masses in nose and nasal sinuses with clinical
      diagnosis of nasal polyp, observed in 10 years, revealed 175 (50.7%) non-
      neoplastic lesions and 170 (49.3%) neoplasms. Among the non- neoplastic lesions,
      there were 110 cases (62.8%) of true nasal polyps including 74 cases (67.3%) of
      allergic polyps and 36 (32.7%) inflammatory ones. The next common non- neoplastic
      polyp was due to rhinosporidiosis (31.4%). Benign neoplastic lesions consisted
      mainly of haemangioma (45.7%), angiofibroma (23.2%), fibroma (6.2%), transitional
      cell papilloma, inverted papilloma, adenoma-3.9% each. Squamous cell carcinoma
      was the commonest malignant lesion encountered (36.6%) followed by 19.5% of
      adenoid cystic carcinoma,17.1% of anaplastic carcinoma and 12.2% of transitional
      cell carcinoma. Adeno carcinoma (4.9%), Mucoepidermoid carcinoma (2.4%), non-
      Hodgkin lymphoma (4.9%) and embryonal rhabdomyosarcoma (2.4%) were the other
      malignant lesions.

PMID- 23119247
TI  - Inverted papilloma of nose and paranasal sinuses -surgical dilemma.
AB  - Inverted Papilloma is a benign neoplasm orginating from the schneiderian membrane
      of nose and paranasal sinus cavities. It has varied clinical and histological
      involving lateral nasal wall, septum, ethmoids, maxillary and sphenoid sinuses
      and at times involves skull base. Interesting three cases are reported because of
      varied presentation of inverted papilloma.

PMID- 23119248
TI  - Histiocytosis-X of fronto-ethmoid region.
AB  - Histiocytosis-X is a rare disease. It occurs mostly in children. Aetiology is
      unknown. Treatment is by surgery, Radiotherapy and Chemotherapy, either singly or
      in combination. Prognosis depends on the degree of involvement. One such case is
      reported and discussed.

PMID- 23119249
TI  - Plasmacytoma of the maxilla.
AB  - Plasmacytoam of maxilla is an extremely rare tumor. Histopathological examination
      led to the final diagnosis. Co-existence of multiple myeloma should be ruled out
      in all such cases. Radiotherapy is the main stay of treatment. A close follow-up
      is needed for clinical evidences of recurrence.

PMID- 23119250
TI  - Traumatic internal carotid artery aneurysm presenting as epistaxis.

PMID- 23119251
TI  - Obstructive sleep apnea syndrome.

PMID- 23119252
TI  - Paraganglioma in the nasopharynx.
AB  - A 50-year old male presented with swollen right eyelids, bleeding per nostrils
      and a vague left post-auricular swelling for 4 months. Posterior rhinoscopy
      revealed one pinkish polypoidal mass in the posterior nare and roof of
      nasopharynx. FNAC from the post-auricular swelling suggested metastatic
      undifferentiated carcinoma. Incisional biopsy was done form the nasopharynx and
      histopathological examination proved it to be a malignant paraganglioma. The case
      is reported for its rarity.

PMID- 23119253
TI  - Intranasal supernumerary tooth.
AB  - Eruption of ectopic and supernumerary teeth into the nasal cavity is quite an
      uncommon condition and may present with varying degree of morbidity. The purpose
      of this short report is to highlight the mode of presentation, management and
      review of relevant literature of this rare occurrence.

PMID- 23119254
TI  - Ameloblastic sarcoma with diverse mesenchymal differentiation.
AB  - This report describes a rare case of ameloblastic sarcoma involving right
      maxilla, with unusual ocular involvement. Diverse mesenchymal differentiation
      towards fibrohistiocytic, fibrosarcomatous and malignant osteoid component along
      with dysplastic dentine observed in the tumour is being reported for the first
      time.

PMID- 23119255
TI  - Dental paraesthesia following intranasal surgery.
AB  - Dental Paraesthesia following intranasal surgery is a definate but ignored and
      ill defined complication, although it is experienced by many patients. A
      prospective study of 325 patients who underwent various surgical procedures on
      the lateral wall of the nasal fossa revealed a complication of dental
      paraesthesia in 85 (26.16%) patients. It has also been observed that dental
      paraesthesia is related with the surgical procedure performed on the patients.
      Dental paraesthesia or pain may distribute from incisor, canine to molar
      region.The area affected by pain Paraesthesia appeares ot have definate
      anatomical basis.

PMID- 23119256
TI  - Malignant schwannoma of nasal cavity.
AB  - A rare case of schwannoma of nasal cavity arising from ethmoid region with
      malignant transformation is reported. It's clinical features histopathology and
      surgical managements are discussed.

PMID- 23119257
TI  - Reconstruction of alae of the nose and angle of the mouth with naso labial flap.
AB  - Naso labial flap is an ideal flap for reconstruction of alae of the nose and
      angle of the mouth after excision for malignancy. Due to inconspicuous deformity
      of the donor area it is ideal in old age. We report our experience in 7 cases of
      basal cell carcinoma of the alae of the nose and 11 cases of carcinoma angle of
      the mouth.

PMID- 23119258
TI  - Cryosurgery in allergic rhinitis.
AB  - Nasal allergy is a common problem difficult to treat. Most of the chronic
      patients feel frustration even after completing all conventional modalities of
      treatment. We have used cryosurgery as an alternative mode of treatment for
      providing the permanent relief with regards to this disease. Cryosurgery
      basically freezes and debulks the hypertrophied inferior turbinates as well as
      the destroys the autonomic innervation, by a cryoprobe at 90 degrees C. This
      study comprises 104 patients of Allergic Rhinitis. The patients were followed up
      for an average period of 3-6 months and the response was evaluated in term of
      relief in three basic clinical presentation namely Rhinorrhoea, Nasal-obstruction
      and Sneezing. Complete cure was obtained in 40.4% cases, Moderate (significant
      improvement in two of the features) in 30.87% cases and satisfactory results in
      19.27% cases were observed. Only 9.67% cases showed no sign of improvement.This
      results infer that cryosurgery may be prescribed as an effective method of
      treatment in patients of Chronic Allergic Rhinitis.

PMID- 23119259
TI  - Juvenile angiofibroma transpalatal approach for intracranial extensions.
AB  - Here we present transpalatal approach for removal of intracranial extensions of
      Juvenile Angiofibroma (JA) of nasopharynx. Modification of standard transpalatal
      approach, it is possible to remove extracranial as well as small intracranial
      tumour. Details of technique, advantages and limitations are presented.

PMID- 23119260
TI  - Management of rhinosporidiosis-newer concept.

PMID- 23119261
TI  - Readers' forum-8.

PMID- 23119262
TI  - Efficacy of histaglobulin on allergic rhinitis.
AB  - Histaglobulin is a non-specific immunotherapeutic agent against allergic
      disorders. At trial study with histaglobulin on allergic rhinitis is featured.
      Histaglobulin was found to be clinically effective against allergic rhinitis. The
      long term efficacy of the drug has to be further studied with the aid of relevant
      investigations. Also other studies have shown that histaglobulin is clinically
      effective against Bronchial asthma.

PMID- 23119263
TI  - Wound healing of autologous implants in the nasal septal cartilage -a verwoerd
      study.

PMID- 23119264
TI  - A disposable device for nasal and pharyngeal local Anesthesia.

PMID- 23119265
TI  - A comparison of cocaine vs lidocaine- oxymetazoline in nasal procedures.

PMID- 23119266
TI  - Eye-sparing protocol in sinonasal cancers -vision at what cost?: Preservation of
      the eye in the treatment of sinonasal malignant neoplasms with orbital
      involvement.

PMID- 23119267
TI  - Noise pollution-an overview.

PMID- 23119268
TI  - Long term language deficiencies in children with otitis media during their first
      year of the life.
AB  - A cohort of lower socio-economic children who experienced multiple and prolonged
      episodes of otitis media (OM) during their first year of life were compared to an
      equivalent group of children who were largely free of OM during their first year.
      Both groups were followed until 9 years of age. The data indicate that children
      with positive histories of OM performed poorer on a variety of Iinguisitc tasks
      across the nine year age span than the children with the positive histories of
      OM. The results suggest that the effect of the otitis media and its accompanying
      hearing loss on communication skills may extend throughout childhood.

PMID- 23119269
TI  - Evaluation of hearing handicap in textile mill employees with noise induced
      hearing loss.
AB  - OBJECTIVE: To calculate hearing handicap in textile mill employees with noise
      induced hearing loss. DESIGN: Cross-sectional study. SETTING: Model Mills, Nagpur
      and Govt. Medical College, Nagpur. PARTICIPANTS: 77 employees with noise induced
      hearing loss. STUDY VARIABLES: Noise levels (by sound level meter), Noise Induced
      Hearing Loss (by audiometry), Hearing handicap (AAOO guidelines). STATISTICAL
      ANALYSIS: Chi square test, Odds ratios, ANOVA. RESULTS: NIHL was significantly
      higher (76.6%) in employees exposed to >85 dB(A) than to 70-85 dB(A) (35.2%) and
      to <70 dB(A) (10.7%) (x(2)=60.6, df=2, p<0.001). Hearing handicap in employees
      with NIHL increased in severity as the noise level increased. Average hearing
      handicap was significantly higher (12.5%) in >85 dB(A) exposure group than 70-85
      dB(A) (7.9%) and <70 dB(A) (4.9%) exposure groups (F=5.17, p <0.05). The risk of
      having hearing handicap >10% was 5.2 times higher in > 85 dB(A) exposure group
      than in <85 dB(A) exposure group (OR = 5.22, 95% C.I. 1.76-15.44). CONCLUSION:
      One third of textile mill employees had hearing handicap. Noise levels >85 dB(A)
      are associated with high proportion as well as greater severity of hearing
      handicap.

PMID- 23119270
TI  - A study of tinnitus profile.
AB  - There are hardly any reports on studies related to nature and types of tinnitus
      carried out in India, nor their seem to be any specific questionnaries developed
      for studying tinnitus. This prompted the authors to undertake the study of
      tinnitus profile with the help of a specially developed questionnaire 35 subjects
      with tinnitus were studied. The obtained data indicates that the severity of
      tinnitus is independent of type and degree of hearing loss. It was further found
      that severity of tinnitus did not vary significantly with subjective complaints,
      the tinnitus neither decreased nor increased with factors like stress, exersion,
      tension, presence of noise, rest and other bodily factors. As the serverity of
      tinnitus increases it was found that the disturbance in sleep, annoyance,
      irritation and subjects botheration increased. However, there were no sex
      variations observed on these factors. Most of the subjects could not recognize
      tinnitus quality interms of pitch, changes in pitch and loudness of their
      tinnitus. Therefore, if these factors are further studied on larger number of
      patients with different otological conditions, it may throw light on clinical
      management of tinnitus.

PMID- 23119271
TI  - Audiovestibular profile in unilateral chronic suppurative otitis media.
AB  - AudioIogical tests including middle ear impedance test and vestibular function
      tests were administered to seventyfive patients of unilateral chronic suppurative
      otitis media. These patients were selected so as to exclude the influence of
      hereditory, drugs, systemic illness and the factors of aging. The subjects were
      subdivided into 3 groups : group 1 cases with central perforation; group 2 with
      marginal and group 3 with attic perforation respectively. On pure tone
      audiometry, 19 diseased ears (25.3%) showed sensorineural hearing loss of 40 dB
      or more at 4 KHz and 8 KHz. The difference in the mean bone conduction threshold
      of diseased and the nondiseased ears was statistically significant at 4 KHz and
      above. Results of specialised tests of hearing suggested cochlear pathology being
      responsible for sensorneural hearing loss. Electronystagmographic recording of
      saccades and bithermal caloric induced nystagmus revealed canal paresis on the
      diseased side in 4 patients (5.3%). These 4 patients had 15 years history of
      otorrhoea.

PMID- 23119272
TI  - Secondary fungal infections in chronic suppurative otitis media.
AB  - A clinical, bacteriological and mycological study of 103 cases of 'safe' chronic
      suppurative otitis media with intractable otorrhoea was conducted to observe the
      role of fungi in the pathogenesis and perpetuation of the disease process.
      Mycotic otitis media was found in 42 cases (40.77%).45 patients with draining
      ears which grew pure bacterial growth were treated with ear drops. Fifteen of
      these patients were treated with topical antibiotics (polymyxin, Neomycin &
      Gramicidin). Other 15 patients were put on antibiotic steroid (Polymxin, Neomycin
      and Hydrocortisone) ear drops. The remaining 15 patients acted as controls with
      dry mopping treatment only.It was noted that prolonged exposure to antibiotic ear
      drops and antibiotic-steroid ear drops led to the growth of pathogenic fungi in 5
      patients (33.33%) each from two study subgroups while the third control subgroup
      of 15 patients grew fungi of low virulence in 3 cases (20%).It was concluded that
      the routine and prolonged use of topical antibiotics or antibiotics-steroids in
      cases of wet 'safe' chronic suppurative otitis media, from the onset is not
      justified.

PMID- 23119273
TI  - Mastoid obliteration using temporo-parietal fascia flap-our experience.
AB  - The management of cholesteatomatous ear disease by open cavity mastoidectomy is
      plagued by a number of cavity problems. A chronically discharging cavity besides
      being a frustrating dilemma to the surgeon is also a social handicap to the
      patient. Obliteration of such discharging cavities seems to be an effective
      therapeutic modality. This paper deals with mastoid obliteration using a
      vascularized axial pattern temporoparietal fascia flap. Twenty post-mastoidectomy
      cases were retrospectively studied for cavity problems and prospectively for
      efficacy of the technique in terms of achieving a dry ear and hearing
      improvement. Also included is an extensive review of literature regarding the
      various causes of cavity problems and techniques of obliteration.

PMID- 23119274
TI  - The anterior tympanotomy.
AB  - The mesotympanum can be approached by the two well known approaches, i.e. (1) the
      (per meatal) tympanotomy, by lifting the posterior annulus tympanicus and (2) the
      posterior tymanotomy, via the facial recess. Based on surgical experience of 1113
      cases, this paper describes in detail the advantages, uses, limitations, possible
      complications, etc., of an (as yet) anonymous approach to the middle ear i.e.
      approaching the middle ear by lifting the anterior annulus tympanicus. The paper
      recommends a possible new nomenclature so as to avoid confusion in our
      understanding of the terminology.

PMID- 23119275
TI  - Retraction pockets in the tympanic membrane - aetiology and management - our view
      point.
AB  - Retraction pockets of the tympanic membrane are believed to be due to eustachian
      tube obstruction or malfunction. Our observations based on intraoperative
      findings suggest that the presence of a large sized mastoid antrum along with
      chronic eustachian tube obstruction plays an important role in the causation of
      retraction pockets. Granular myringitis may also occur in these circumstances
      when there is a recurrent eustachian tube blockage due to infection especially if
      the patient has received frequent and inadequate courses of antibiotics. The use
      of chromic catgut to create a healed air-filled middle ear space along with a
      canal wall down tympanomastoidectomy is discussed for their effective treatment.

PMID- 23119276
TI  - Congenital incudostapedial malformation.
AB  - A case of bilateral symmetrical conductive deafness in a 45 year old female is
      presented. Tympanotomy revealed an anomaly involving the incudostapedial complex.
      The case is reported both because of rarity and also the anomaly encountered
      makes it apparently unique.

PMID- 23119277
TI  - Laser-doppler evaluation of the human tympanic membrane by measuring blood flow,
      volume, and velocity.
AB  - From a hospital setting, a sample base of 50 people with normal hearing, was used
      to study the otoacoustic phenomenon of the ear. Human volunteers were taken into
      an acoustic room and allowed to rest for 5 minutes. Each volunteer inserted a
      probe as close to the tympanic membrane as possible. The objective of the study
      was to determine the pattern of distribution of blood flow, volume, and velocity
      of erythrocytes circulating in blood vessels of the tympanic membrane. This was
      achieved by recording numerical values for the flow, volume, and velocity of
      erythrocytes using the laser-Doppler flowmeter. Analysis of the results showed
      two distinct relationships, a negative exponential curve in the blood flow for
      the right and left ear, and a Gaussian distribution for the velocity and volume
      of erythrocytes for both ears.

PMID- 23119278
TI  - Glomus intravagale tumour-a case report.
AB  - Paragangliomas are uncommon tumours arising from chemoreceptor organs. Those
      arising in relation to the vagus nerve are referred to as Glomus intravagale or
      vagal body tumours. They are rare tumours accounting for only 3% of Head & Neck
      paragangliomas. A case of Glomus intravagale tumour is presented both in view of
      its rarity and to stress its differentiation from a carotid body tumour which in
      this case was possible only at the time of surgery.

PMID- 23119279
TI  - A cutaneous horn over seborrhoeic keratosis of pinna.
AB  - Cutaneous horn is not rare. Many varieties of cutaneous horns have been
      described. Seborrhoeic keratosis of pinna is not very common especially with a
      cutaneous horn developing over it. We encountered a cutaneous horn, over
      seborrhoeic kerotosis involving pinna, an uncommon finding.

PMID- 23119280
TI  - Study of prevalence and aetiology of the hearing loss amongst school going
      children.
AB  - School survey study to assess the prevalence rates and aetiological factors
      causing hearing loss among children in and around Pune Cantonment covering urban
      and semiurban population has been carried out. We encountered deafness prevalence
      rate of 11.7% and chronic suppurative otitis media (4.75% of the deaf children)
      the commonest cause. Maximum number of patients were in age group of 6-11 years
      and semiurban children and those from lower socio-econimic group had higher
      prevalence rate as compared to urban children and those from upper socio-econimic
      group. Relevant suggestions for prevention and management of deafness have been
      made. This study emphasizes the fact at most of the aetiological factors in
      causing hearing impairment in school going children are treatable and hence
      deafness can be prevented to a large extent if remedial measures are taken in
      time.

PMID- 23119281
TI  - Composite graft tympanoplasty.
AB  - Seventy six ears with chronic suppurative otitis media and fit for tympanoplasty
      were subjected to grafting with combination of perichondrium and cartilage
      (composite graft) for restoration of sound conducting apparatus and
      reconstruction of canal wall. A comparison with temporal fascia grafting has been
      done. Composite graft procedure gave better functional improvement, helped in
      reconstruction of canal wall and was also useful in elimination of retraction
      pockets.

PMID- 23119282
TI  - Small cell carcinoma (Metastasising to the temporal bone).

PMID- 23119283
TI  - Closure of tympanic membrane perforations by chemical cautery.
AB  - Fifty cases of dry, central, tympanic membrane perforation were studied for
      closure by application of saturated solution of trichloracetic acid.
      Aetiologically 17 cases belonged to traumatic and 33 to the inflammatory group.
      Eustachian tube patency and good air-bone gap on audiometry were the pre
      requisites. Study concluded with 78% success with average of 2.8 applications.
      The patients had definite improvement in the hearing acuity and relief from other
      symptoms. The study highlights the achievements by using this old method.

PMID- 23119284
TI  - Tympanosclerosis-how we look at it.
AB  - Tympanosclerosis (TS) is a common sequelae of chronic otitis media found in all
      age groups. Over a period of 3 years, out of 520 surgical cases, 68 (13%) were
      found to have varying amounts of Tympanosclerotic plaques (TSP) warranting
      surgical removal. 60% had extension of TSP over the ossicular chain thus
      affecting its mobility. Deliberate surgical removal of TSP was undertaken for
      hearing improvement.Systematic and meticulous removal of TSP rather than en-bloc
      removal has been found to improve the hearing as close to as in, non
      tympanosclerotic ear surgery.

PMID- 23119285
TI  - Glomus jugulare.
AB  - Glomus Jugulare tumours are relatively rare. In the early stages the symptoms may
      simulate other otological conditions such as acute otitis media. We report a case
      of a 34 year old male with Glomus Jugulare, where the diagnosis was initially
      missed and later made on development of classical symptoms. The management of
      this case and a brief review of literature is presented. The aim is to highlight
      the importance of early diagnosis and successful outcome following surgery.

PMID- 23119286
TI  - An unusual foreign body in the mastoid process.
AB  - The interest in reporting this case is the unusual manner in which the foreign
      body entered the mastoid process without any clinical symptoms and remained
      covered by the skin from outside. Plastic refill of the dot pen (metallic end)
      pierced the mastoid bone in a child is rather atypical due to a fall.

PMID- 23119287
TI  - Vestibulo-cochlear functions in diabetes mellitus.
AB  - Vestibulo-cochlear functions in 30 diabetics and 30 controls were evaluated.
      Hearing loss mild to moderate was detected in 40% of diabetics. This was
      typically bilateral symmetrical, more in high frequencies and cochlear in nature.
      Incidence of hearing loss was more in higher age groups, in poorly controlled
      diabetics, and in those without a family history of diabetes. There was no
      correlation between hearing loss and duration of diabetes. There was no evidence
      of vestibular dysfunction in the diabetics studied.

PMID- 23119288
TI  - Impulse noise trauma during army weapon firing.
AB  - A 100 infanty personnel firing modern weapons such as the Anti Tank Guided
      Missile, 106mm Recoiless Gun (RCL), 84mm Rocket Launcher (RL) and 81mm Mortar
      were studied for the effect of impulse noise on the ear and the evolution of the
      Temporary Threshold Shift (TTS), Recovery Time (RT) and Permanent Threshold Shift
      (PTS) was traced.

PMID- 23119289
TI  - Unilateral deafness in mumps how i perceive it?

PMID- 23119290
TI  - current opinion: Intratympanic gentamicin therapy for meniere's disease.

PMID- 23119291
TI  - Can a good otologist be a good endoscopist?

PMID- 23119292
TI  - Readers' forum-9.

PMID- 23119293
TI  - Betahistine.

PMID- 23119294
TI  - More about topioca and rhinosporidiosis.

PMID- 23119295
TI  - Letter to the editor.

PMID- 23119296
TI  - Letter to the editor.

PMID- 23119297
TI  - Wilde, sir william robert willis.

PMID- 23119298
TI  - Hundred years of laryngology.

PMID- 23119299
TI  - From mirror to microscope and there after.

PMID- 23119300
TI  - Laryngeal reinnervation surgery - results of a selective approach in an animal
      study.
AB  - Laryngeal reinnervation surgery is a difficult subject due to the fact that the
      recurrent laryngeal nerve (RLN) is responsible for both adductor and abductor
      laryngeal activity. Non-selective reinnervation procedures will result in
      laryngeal synkinesis with restoration of tonicity. Restoration of mobility
      requires selective reinnervation of the adductor and abductor branches with
      nerves with similar activity patterns as the initial abductor and adductor
      branches of the RLN.

PMID- 23119301
TI  - Malignancy of the larynx: (Experimentation on Animal, Construction of Biologic
      Neo-Larynx and Rehabilitation of the Laryngectomee-20 Years Experience).
AB  - Squamous cell carcinoma is by far the commonest malignancy of the larynx and I
      would confine my present paper mainly to this along with the management and post
      operative rehabilitation after total laryngectomy. High survival rate in majority
      of the cases, if diagnosed and treated early and adequately, provokes and
      encourages the interested laryngologist to consider not only about performing
      effective surgery, including on those cases where radiotherapy is inadequate or
      has failed, but also resorting to rehabilitative surgical procedures after total
      laryngectomy with or without neck dissection, offering to the laryngectomee a
      'Biologic' Neo-Larynx, created from the patients own tissues, for tracheo
      oesopharyngeal phonation.I am of the opinion that if a Neo-Larynx is constructed
      from the upper parts of the patient's own trachea and oesophagus without using
      any extraneous synthetic material, the patient would be happy to learn that the
      new voice box has been created out of his own tissues and no extraneous foreign
      material has been implanted and left in his body and he can effortlessly phonate
      'tracheo-oesophageally' instaneously after removal of the silastic sheet from the
      Neoglottis five weeks after the operation without any rigorous training and the
      voice is better than the conventional alaryngeal 'pharyngo-oesophageal' one after
      total laryngectomy. Moreover, the complications associated with the prostheses
      viz. fungal and bacterial invasion with subsequent leakage around it and its
      displacement, and the tedious maintenance and replacement problems can be
      obviated by providing the patient with a 'biologic' Neo-Larynx of viable
      tissues.Therefore, my present paper will deal with the construction of Neo-Larynx
      after conducting experiments on animals. In the Neo-Larynx, a Neo-Epiglottis
      (hitherto not reported in the literature to my knowledge) and a Neo-Glottis are
      ingeniously constructed in order to enable the laryngectomee to phonate
      tracheooesophageally (c.f. pharyngoesophageally). The Neo-Glottis is transversely
      disposed since it offers better protection against aspiration than the vertically
      disposed one. The Neo-Epiglottis is constructed from the posterior tracheal wall,
      inferiorly based, or from the superiorly based tongue-shaped flap, raised from
      the full-thickness membranous posterior tracheal wall, or from the anterior
      tracheal wall, folded posteriorly (as in 'Duck-Bill' Neo-Larynx), for preventing
      aspiration through the Neo-Glottis into the tracheaobronchial tree during
      deglutition. In addition, a statico-dynamic sphincter or sling, reminiscent of
      the original primitive one, has been constructed around the Neo-Larynx, utilizing
      the strap muscles of the neck, in order to bring about competency of the Neo
      Larynx for preventing aspiration through the Neo-Glottis. By this operation the
      problems of aspiration and stenosis of the Neo-Glottis have been largely solved.
      The Neo-Glottis is constructed in a transverse slit in the anterior oesophageal
      wall in a protective gutter in the anterior wall of the oesophageal lumen and the
      inferior lip of the slit is reinforced with a small cartilage bar in order to
      make it a stiff neo-vocal cord for producing stronger and better voice than
      pharyngo-oesophageal one which (i.e. tracheo-oesophageal one) is akin to normal
      voice. Presumably, the sphincter influences the voice quality by its continuously
      changing tension. The upper end of the trachea is closed to form a cul-de-sac and
      the phonetic stream is stopped here and channelised through the only available
      outlet i.e. the tracheooesophageal fistula (Neo-Glottis) into the oesophagus and
      pharynx for articulation.The latest proposed procedure is easier than the
      previous ones in which a biologic 'Duck-Bill' Neo-larynx is constructed from the
      upper parts of the trachea and oesophagus. Neo-Epiglottis and Neo-Vocal cords are
      incorporated in this. The Neo-Glottis is situated in the trachea anterior to the
      tracheo-oesophageal fistula. In this there are two additional phonatory
      mechanisms through which the phonetic stream passes :The two tracheal flaps,
      projecting into the oesophageal lumen, vibrate during phonation.Pseudoglottis at
      cricopharyngeus level.It is presumed that these, by producing harmonics, enrich
      the voice produced by the Neo-Glottis. Voice would be good with inflectional
      patterns and aspiration and stenosis problems would be significantly minimized.

PMID- 23119303
TI  - Correction of dysphonia using laryngeal framework surgical techniques.
AB  - Many dysphonias caused by incomplete glottis closure or inadequate vocal fold
      tension are eligible for phonosurgical correction. Most phonosurgeons presently
      advocate laryngeal framework surgery as the first treatment of choice.For
      correction of incomplete glottis closure usually thyroplasty type 1 and arytenoid
      adduction techniques are used. For correction of vocal fold tension crico-thyroid
      approximatidn and thyroplasty type 3 can be used. Often combinations of different
      techniques are required to achieve the best result. It is therefore essential to
      perform these procedures under local anaesthesia, so that the voice can be
      monitored during the surgery and so that the surgery can be tailored to the
      patient's voice.89 patients underwent laryngeal framework surgery, 85 of them for
      correction of incomplete glottis closure, which in 75 patients was due to
      unilateral vocal fold immobility. The results in this group were good also in
      long term follow-up. Complications were few and insignificant.

PMID- 23119304
TI  - Management of airway problems in severely burned patients.

PMID- 23119302
TI  - The "gregorio maranon" hospital experience in the treatment of laryngeal
      carcinoma.
AB  - A retrospective analysis has been carried out of 4100 patients with
      pharyngolaryngeal carcinoma who were seen at the Hospital Gregorio Maranon
      between 1962 and 1993. 1287 patients were excluded from this study, leaving 2813
      patients available for analysis. The great majority of the 2813 pharyngolaryngeal
      carcinomas were primary laryngeal tumours (2519). These are the subject of our
      study.We present our theoretic protocol for treatment of laryngeal carcinoma,
      both glottic and supraglottic, with special attention to the partial surgery. Our
      oncological and functional results are presented and discussed.

PMID- 23119305
TI  - Medialization laryngoplasty with silastic implant in unilateral vocal cord
      paralysis.
AB  - The state of art of Laryngoplastic surgery gaining day to day importance where
      Rhinoplasty stood almost a century ago. Medialization Laryngoplasty using
      Silastic Implant for the correction of symptomatic unilateral vocal cord
      paralysis is discussed.

PMID- 23119306
TI  - Basaloid squamous cell carcinoma - larynx.
AB  - Basaloid squamous cell carcinoma is a rare variant of squamous cell carcinoma,
      Larynx has been an uncommon site of this tumour which is said to have aggressive
      biological behaviour with high incidence of cervical and distant metastasis along
      with second primary. Two cases of laryngeal basaloid squamous cell carcinoma are
      reported with relevant review of literature. The submucosal spread of tumour is
      highlighted alongwith role of preoperative radio therapy.

PMID- 23119307
TI  - Airway management in acute infectious croup syndromes.
AB  - The article presents the author's experience with airway management of 500
      children with acute infectious croup and epiglottitis over a 7-year period in a
      teaching hospital setup. A policy of early elective protective intubation under
      controlled condition for children with severe croup and epiglottitis, in a
      multidisciplinary intensive care setting resulted in a satisfactory outcome.
      Recent developments in the field are discussed; these include non-invasive
      monitoring, medical treatment options for viral croup with parenteral high dose
      dexamethasone and nebulized adrenaline, newer broad-spectrum antimicrobials for
      drug-resistant bacterial infectious and an effective vaccine against Hemophilus
      influenzae type b. These hold the promise of reducing morbidity and mortality
      from acute infectious croup syndromes even in situations with limited surgical
      and monitoring facilities.

PMID- 23119308
TI  - Spontaneous expulsion of schwannoma of epiglottis.
AB  - A rare case of spontaneous expulsion of schwannoma of epiglottis is being
      reported. These are neurogenic tumours arising from the schwan sheath of
      peripheral, cranial and sympathetic nerves. The great majority of these
      neurogenic tumours originate from aryepiglottic fold or false vocal cords.
      However the neurofibroma of the epiglottis are quite uncommon.

PMID- 23119309
TI  - Study of benign glottic lesions undergoing microlaryngeal surgery.
AB  - A Study of 67 patients with the complaint of hoarseness of voice was undertaken.
      Patients with apparently benign laryngeal lesions were selected and subjected to
      microlaryngeal examination. The benign lesions were categorised and effect of
      smoking, pollution, occupation and vocal abuse noted. The beneficial effect of
      speech therapy was also evaluated.

PMID- 23119310
TI  - Adenoid cystic carcinoma of larynx.

PMID- 23119311
TI  - Cysticercosis of larynx.
AB  - A rare case of cysticercosis of larynx in a 50 years male presenting with
      hoarseness of voice is reported.

PMID- 23119312
TI  - Recurrent laryngeal lipoma.
AB  - A rare case of laryngeal lipoma is reported with review of literature. We
      describe our technique of intra laryngeal excision of this tumour by
      microlaryngeal dissection.

PMID- 23119313
TI  - Laryngeal chondroma.
AB  - Chondroma of thyroid cartilage is a rare condition. Two cases of laryngeal
      chondroma diagnosed clinically and confirmed histopathologically are presented.
      Surgical excision was undertaken in both the cases.

PMID- 23119314
TI  - Readers' forum-10.

PMID- 23119315
TI  - Itraconazole - a potent antifungal drug.
AB  - Itraconazole is an orally active triazole antifungal drug which has demonstrated
      a broad spectrum of activity and a favourable pharmacokinetic profile. It is a
      potent inhibitor of most human fungal pathogens including Aspergillus species.In
      non comparable clinical trials, Itraconazole was shown to be extremely effective
      in a wide range of superficial and more serious deep fungal infections when
      administered once or twice daily. Preliminary findings also indicate that
      itraconazole, may hold promise for the prophylaxis of opportunistic fungal
      infections in patients at risk, i.e. women with recurrent vaginal candidiasis,
      AIDS patients and patients receiving immunosuppressant drugs.

PMID- 23119316
TI  - Vocal fold submucosal infusion technique in phonomicrosurgery.

PMID- 23119317
TI  - Letters to the editor.

PMID- 23119318
TI  - Notable men in ent.

PMID- 23119319
TI  - Fifty years ago.

PMID- 23119320
TI  - A study of otorhinolaryngological manifestations in patients of chronic renal
      failure.
AB  - The present study was carried out on 50 patients of Chronic renal failure (CRF),
      Majority of CRF patients had high frequency hearing loss, but inner ear changes
      were found to be irreversible even after dialysis. All cases had cochlear lesion.
      No relationship could be established between the level of blood urea, creatinine,
      serum potassium, serum calcium and blood pressure with the severity of the
      impaired hearing. A direct correlation was seen between increasing hyponatraemia
      and impaired hearing. No direct relationship could be made between blood pressure
      and epistaxis, but all the cases had raised blood urea.

PMID- 23119321
TI  - Otology in India - 50 years ago.

PMID- 23119322
TI  - Neck dissection alternatives.

PMID- 23119323
TI  - Antibodies to p53 may predict a high risk of treatment failure in head and neck
      cancer.
AB  - Overexpression of p53 as well as the occurrence of serum p53 antibodieshave been
      correlated to shorter survival and relapse-free intervals in head and neck
      squamous cell carcinoma (HNSCC). The aim of this study was to reconsider the
      clinical implications of serum p53 antibodies in HNSCC. Two matched study groups
      (n=78 patients with HNSCC each), one group positive and one negative for serum
      p53 antibodies, were followed-up (median of 3 years) regarding the occurrence of
      relapses, second primaries and tumor related deaths. Tumor relapses (n= 27 vs.
      12), second primaries (n= 76 vs. 4) and tumor related deaths (n=21 vs. 9)
      occurred more frequently in the seropositive group. The results of this study
      indicate that the presence of serum p53 antibodies in patients with HNSCC points
      out a group of patients, who have a high risk of treatment failure.

PMID- 23119324
TI  - CT and US features of cervical lymphadenopathy due to kikuchi's disease.
AB  - Kikuchi's disease or histiocytic necrotising lymphadenitis is a distinct benign
      clinicopathologic entity which is to be distinguished from malignant conditions,
      especially lymphoma.We report a young woman with Kikuchi's disease presenting
      with cervical lymphadenopathy and mild hepatomegaly. CT and US findings are
      presented as well as a review of the pertinent literature.

PMID- 23119325
TI  - Schwannoma of submandibular region.
AB  - Tumours of the nerve sheath origin in the head and neck are not common.
      Schwannomas are rare. Only a few cases have been reported so far. We report a
      rare case of Schwannoma of Submandibular region arising from the lingual nerve.

PMID- 23119326
TI  - Effect of radiation on oropharyngeal flora in patients of head and neck cancer.
AB  - In the present study 124 cases of head and neck cancers subjected to radiation
      therapy were studied and the change in oropharyngeal flora with the radiation
      therapy noted. 50 cases for comparison with no ENT complaints were taken control.
      The oropharyngeal flora in the control cases was established as the normal flora.
      Any other floral constituent was considered to be abnormal oropharyngeal flora.
      It was found that with radiation there was a statistically significant increase
      in several constituents of normal as well as abnormal oropharyngeal flora. This
      increase could be the predisposing factor for post radiation infections
      especially in post operative patients. Oropharyngeal swabs were sent before,
      during and after radiation therapy for detailed bacterial and mycotic flora smear
      and culture examinations.

PMID- 23119327
TI  - Incidence of occult primary-their diagnosis and non surgical management.
AB  - Twenty one (16.5%) cases of Occult primary (18 males and 3 females) were analysed
      out of 121 cases of secondaries in the neck regarding their diagnosis and non
      surgical management over a period of six years, from March, 1990 to Feb., 1996 in
      the department of ENT and Radiotherapy of I.G.M.C. and Hospital Shimla. Majority
      of these cases were in the age group of 50-70 years and 95% of these cases had
      squamous cell carcinoma and in one case there was adenocarcinoma. 12 (57%) of
      these patients were in N3 stage. 13 patients were treated by radiotherapy, 3 by
      chemotherapy whereas remaining 5 cases absconded and therefore no treatment could
      be given to them.

PMID- 23119328
TI  - Anterior skull base surgery-our experience.
AB  - Anterior skull base surgery is now an accepted treatment modality for many
      lesions involving the anterior skull base including the pituitory region. This
      paper deals with a fifteen year experience over various approaches to the
      anterior skull base, and thereby trying to rationalize the appropriate approach
      for the tumours in different anatomical situations. Relevant literature has also
      been reviewed.

PMID- 23119329
TI  - Rhabdomyosarcoma of parotid gland.
AB  - A rare case of rhabdomyosarcoma of parotid gland in a child is being reported
      along with a brief review on its incidence, presentation, management and.

PMID- 23119330
TI  - Branchial cleft fistulae.
AB  - Three rare and interesting cases of complete branchial cleft fistulae including
      two cases with unusual presentation are reported. Total excision of the fistulae
      was carried out by step ladder technique in all the three cases resulting in
      their successful surgical management. Relevant available literature on the
      subject has been reviewed.

PMID- 23119331
TI  - The pectoralis major myocutaneous flap in head and neck reconstruction.
AB  - The pectoralis major myocutaneous flap (PMMC flap) represents a landmark in the
      development of head and neck reconstructive surgery. After Stephan Ariyan first
      described its use for head and neck reconstruction in 1979, it has become
      tremendously popular and has revolutionised head and neck cancer surgery. Here,
      we present our initial experience with fourteen PMMC flaps in head and neck
      reconstruction. In most of the instances it was used for oral or oropharyngeal
      reconstruction. It was used for five other reconstructive tasks as well. Wound
      infection was the most common complication. There was no case of total flap loss.
      It has proven to be a reliable method of reconstuction in the head and neck.

PMID- 23119332
TI  - Pectoralis major rib osteomyo cutaneous flap in primary mandibular reconstruction
      in floor of the mouth cancer.
AB  - We report pectoralis major rib osteo myocutaneous flap in reconstruction of
      cancer floor of the mouth in 8 cases. We have discussed it's advantages in
      country like ours over the micro vascular graft. The rib (Vascularised bone
      graft) incorporated in this flap gives ideal support for mandibular arch
      reconstruction.

PMID- 23119333
TI  - FIbrous dysplasia of right upper jaw - uncommon presentation.
AB  - 30 years, male patient presented with huge nasal mass for 25 years and nasal
      obstruction for 15 years. On examination, a mass of 10" * 8 " size found
      involving the right side of face, nose, cheek, orbit and palate. The right eye
      was proptosed eccentrically and was completely blind. Histopathological
      examination confirmed it as fibrous dysplasia.

PMID- 23119334
TI  - Congenital teratoid tumour of nasopharynx with cleft palate.
AB  - A case of congenital nasopharyngeal teratoid tumour presenting since birth
      projecting into oral cavity through the palatal cleft and gradually increasing in
      size thus causing breathing and feeding difficulty in a four months old female
      child is presented here for its rarity. A brief review of literature and
      management of such patients is also discussed here.

PMID- 23119335
TI  - Pathological fracture of the mandible, secondary to eosinophilic granuloma in a
      medically compromised patient.
AB  - A case of eosinophilic granuloma of the mandible with submandibular lymph node
      involvement in a medically compromised patient is presented. The lesion caused
      the pathologic fracture of the. mandible. It was treated radically with the
      resection of the mandible between the angle posteriorly and the midline
      anteriorly and immediate reconstruction with a 3DBDB AO reconstruction plate.
      This was followed by telecobalt therapy of 2000 cGys in 10 fractions over 20
      days.The combined surgical and radiation therapy should be reserved for patients
      having: (1) unremitting pain following currettage (2) Limitation of activity (3)
      a medically compromised patient or (3) in whom radiographic findings suggest an
      aggressive lesion involving adjacent tissues and/or causing pathologic fractures.

PMID- 23119336
TI  - Multiple tumors in head and neck region.

PMID- 23119337
TI  - Recurrent cervical abscess due to pyriform sinus fistula-a case report.
AB  - The pyriform sinus fistula is rare congenital anomaly of either third or fourth
      branchial pouch, which most frequently presented itself by recurrent episodes of
      neck abscess for long time. Majority of patients with this anomaly presented with
      symptoms before 10 years and it is more common than has previously been commonly
      found on leftside (93%). Clinically high index of suspicion, cannulation of the
      tract under general anaesthesia, Direct laryngoscopy and fistulogram have
      freequently been successful in identifying the presence of these embryological
      remnants. Surgical exploration of sinus tract with its total excision, guided
      with cannula inside its lumen is the definitive treatment.

PMID- 23119338
TI  - Giant Cervical Osteophytes Their Significance in ENT Practice.
AB  - Foresteir's disease or Diffuse idiopathic skeletal hyperostosis (DISH) involving
      the cervical vertebrae in two patients is being presented as an uncommon cause of
      snoring and dysphagia. The radiological features of the giant osteophytes
      involving the cervical vertebrae are detected on routine skiagrams of the neck. A
      review of literature over ten years showed no such record of such a lesion
      occurring in C1-C2 vertebrae, whereas the occurrence in the lower cervical
      vertebrae is occasionally seen causing dysphagia. The relative merits of the
      surgical approaches are discussed.

PMID- 23119340
TI  - Clinico-pathological correlation study of cervical lymph node masses.
AB  - One hundred and ten cases of cervical lymph node masses were subjected to
      clinical evaluation and aspiration cytology. Eighty six cases which subsequently
      underwent open biopsy were subjected to histopathological evaluation. Accuracy,
      specificity and sensitivity of clinical diagnosis were 86.1%, 93.6% and 91.1%
      respectively as compared to 88.3%, 97.6% and 93.6% respectively for aspiration
      cytology. Reliability coupled with other advantages makes aspiration cytology the
      first line investigation in evaluating cervical lymph node masses reserving open
      biopsy for certain specific indications. Based on the conclusions a protocol is
      being recommended for evaluation of cervical lymph node masses.

PMID- 23119339
TI  - Hemifacial microsomia.
AB  - Congenital abnormalities of face emerge as a constellation of malformation of
      structures which arise from the first and the second branchial arch and the
      intervening first pharyngeal pouch and the primordia of the temporal bone. When
      fully expressed, a patient with hemifacial microsomia [Syn: otomandibular
      dysostosis] exhibits usually unilaterally under developed external or middle ear,
      mandible, zygoma, maxilla, temporal bone, facial muscles, muscles of
      masticiation. Many cases however, have been reported where the syndrom is not
      fully expressed (Crabb 1965).

PMID- 23119342
TI  - Mandibular mucoperiosteal flap.

PMID- 23119341
TI  - Calcifying odontogenic cyst.

PMID- 23119343
TI  - Readers' forum-11.

PMID- 23119344
TI  - Sparfloxacin: An Overview of Its Efficacy in ENT Infections.

PMID- 23119345
TI  - Furlow palatoplasty-double opposing z-plasty.

PMID- 23119346
TI  - Letters to the editor.

PMID- 23119347
TI  - From the desk of the editor.

PMID- 23119348
TI  - Tinnitus - Modern management.

PMID- 23119349
TI  - Neurootology - today.

PMID- 23119350
TI  - Trans and peripetrous surgery.

PMID- 23119351
TI  - Neurootological differential therapy for vertigo patients.
AB  - Major neurootological complaints, which mostly need drug treatment, are:
      giddiness, dizziness, hearing loss and tinnitus. The neurootological differential
      diagnosis is the basis for planning the mostly supportive treatment of vertigo
      patients. In planning the therapy, we are utilizing a computerbased expert system
      Clamedex for establishing the neurootological diagnosis through history, ORL
      inspection, ENG, calorics, rotatory chair test, cranio-corpo-graphy (CCG),
      optokinetics, psychophysical audiometry, acoustic brainstem and late evoked
      potentials, visually evoked potentials etc. On this knowledge base we are
      designing an individually adapted case oriented drug therapy.Nausea and vomitus
      are the important subjective complications of dysequilibrium states. Therefore
      antivertiginous and antiemetic therapies have to be applied if necessary. Usually
      the duration is of limited time.Other drugs being chosen for a supportive
      pharmaco therapy according to the functional topodiagnostics of the lesions
      usually possess one or more of the following actions upon the equilibrium
      regulating network:increase of cerebral blood flow,enhanced penetration through
      the blood brain barrier,increase of neuronal metabolism andstabilization of
      specific neurotransmitters.The neurootological patients are treated and monitored
      by regular neurootometric follow up investigations.

PMID- 23119352
TI  - Paramedian pontine reticular formation and electronystagmography.

PMID- 23119353
TI  - Evaluation of hearing loss in at risk neonates by evoked otoacoustic emissions.

PMID- 23119354
TI  - Bera in normal neonates and infants: (Some observations on maturation of auditory
      pathways).
AB  - This study includes eight normal, not at-risk for deafness, neonates and infants
      of age ranging from 2 days to 1 year. BERA was done at 2 kHz. frequency at 80 dB
      intensity. In the majority of the subjects, only wave I, II, III and V could be
      definitely identified. It was observed that latencies of waves decreased as age
      of neonate/infant increased. Decrease of latency was more marked in first 6
      months of life (wave V from 7.2 ms to 6. / ms) as compared to next six months
      (wave V from 6. 1 ms to 5.9 ms). This could be because of rapid myelination in
      the first six months of life.

PMID- 23119355
TI  - Value of blink reflex in assessing V and VII nerve function in patients with C.
      P. Angle tumours- a prospective study of 75 patients.
AB  - This propsective study analyses the role of blink reflex (BR) in 75 patients with
      Cerebellopontine Angle (CPA) tumours. The aim was to find out the subclinical
      involvement from the blink reflex findings. Fifth nerve was clinically involved
      in 82.7% patients while, BR was able to detect afferent abnormality only in 54%
      patients. The seventh nerve was clinically involved in 74.7% and blink reflex
      could detect the efferent abnormality is 72% patients. Thus,
      clinicoelectrophysiological correlation was 56.4% and 72% for V and VII nerve
      respectively. In the patients in whom there was no V or VII nerve involvement BR
      showed VII nerve involvement in 12% patients. The subclinical involvement of the
      V nerve and the brainstem were detected by BR in 4% patients each. In conclusion
      BR is good test for the assessment of VII nerve function as compared to V nerve
      function. BR could pick of subclinical involvement in 20% patients.

PMID- 23119356
TI  - Bera study in 150 children under five years age.
AB  - BERA (BSER OR BAEP) has proved to be useful tool in diagnosing hearing
      impairments in children which could be conductive or sensorineural in nature.
      Because of early detection the rehabilitative procedures could be started early
      which will help speech and language development.We have studied 150 cases below 5
      years age and our observations are recorded with case history profile like high
      risks, referral for adoptions, congenital malformations and delayed speech. We
      fell Bera is the only tool which can give accurate picture of hearing
      sensitivity.

PMID- 23119357
TI  - Assessment of traffic Noise and its impact on certain personnel.
AB  - The Noise measurements done during peak traffic hours in Chennai city in 1985, is
      compared with the levels prevailing in 1993 and the density of vehicles plying
      enumerated. The intensity of noise produced was found to be proportionate to the
      density of the vehicles. Noise levels at all points studied have shown a
      significant increase in the last eight years, varying from 2 dB to 10 dB. In most
      of the places the levels were found to be above 80 dB.A sample study of 100
      individuals, selected from a survey comprising of 1100 traffic policemen, showed
      a high incidence (21 %) of noise induced hearing loss. Incidence of high
      frequency sensorineural hearing loss (18%) was also found to be high in these
      personnel.Possible causes for these findings are discussed and some remedial
      measures suggested.

PMID- 23119358
TI  - Acoustic biast trauma.
AB  - In this study 26 cases of blast injury to ear were studied. Both ears were
      affected in 9 cases and therefore the number of ears studied being 35. The
      audiological findings along with the treatment and a followup of 2 years is
      presented.We found that mixed deafness was commonest and the sensorineural
      element of the hearing loss started recovering before conductive element, but
      recovery slowed down later on and was incomplete in most cases. Approximation of
      torn fragments of tympanic membrane improved its healing. Vertigo lasting for 1-7
      days was present in 46.15% of cases. Only one patient had perilymph fistula which
      was repaired.

PMID- 23119359
TI  - Study of auditory brainstem responses in presbyacusis.
AB  - The results of auditory brainstem evoked responses in 25 subjects of presbyacusis
      are compared with 25 age and sex matched controls. Absolute latent periods of
      wave I through V were significantly prolonged in presbyacusis group. Delayed wave
      I and no significant change in interwave interval latencies of I-V, III-V and
      mild shortening of interwave interval of I-III in presbyacusis is observed.

PMID- 23119360
TI  - Ear, nose and throat manifestations in Laurence-Moon-Biedl-Bardet Syndrome.
AB  - Laurence-Moon-Biedl-Bardet Syndrome is a rare hereditary autosomal recessive
      disease. It is clinically characterised by a pentad of congenital defects e.g.
      poly or syndactyly, mental retardation, obesity, hypogenitalism and retinitis
      pigmentosa. Five cases of the syndrome with additional ENT features are
      presented. The salient features of the condition are discussed in the light of
      available literatures.

PMID- 23119361
TI  - Tinnitus: Our experience with intratympanic instillation of 2% Xylocaine.
AB  - Idiopathic subjective tinnitus is quite an obscure otopathology for over the
      decades. This paper deals with the results of an intratympanic instillation of 2%
      Xylocaine through Grommet over a six weeks time. Patients overall compliance was
      26%. We suggest this method of treatment for those who have been treated
      unsuccessfully with drugs, acupuncture, electrical control, biofeedback etc with
      not much reward. Patient is warned about impending nausea and vomiting. Tinnitus
      is alleviated to cope with near to normal life.

PMID- 23119362
TI  - Fluctuant hearing loss.
AB  - 122 cases of fluctuant hearing loss were studied. Serous otitis media was
      commonest followed by Meniere's disease, Acoustic neuroma, fistula of round and
      oval window, oto-mandibular syndrome, Congenital cholesteatoma and maxillary
      sinusitis. Cases of Arachnoid cyst, Multiple sclerosis, abnormalities of base of
      skull and craniocervical region and cervical rib causing fluctuant hearing loss
      could not be detected. Aetio pathophysiology of all discussed.

PMID- 23119363
TI  - Bera in high risk children a 5 year hearing evaluation.
AB  - Very few studies have been done all over the world to find out incidence of
      hearing loss associated with different risk factors. The objective of this study
      was to find out incidence of hearing loss in children from High Risk category
      especially in reference to individual risk factor. Out of 593 children (0-5 year)
      from High Risk category subjected to B.E.R.A. over last 5 years, 126 (21.4%)
      showed hearing loss. 202 children (34.06%) from Birth Asphyxia category formed
      the largest group. Patients with Head and Neck anomaly showed maximum hearing
      loss (91.66%). 101 (80.15 %) children showed bilateral hearing loss. 57 Ears
      (4.80%), 67 Ears (5.64%), 99 Ears (8.34%) showed Mild, Moderate and Severe
      hearing loss respectively. 152 ears (71.31%), 67 ears (29.90%), 4 ears (1.79%)
      showed Cochlear, Retrocochlear and conductive hearing loss.

PMID- 23119364
TI  - Cortical deafness following head injury -a case report.
AB  - Cortical deafness is a rare entity. Only few case reports are available. In this
      paper, a case of right fronto-temporal contusion following head injury causing
      bilateral cortical deafness has been reported. Most of the cases reported in the
      past were because of cerebral infarcts due to arterial occlusion.

PMID- 23119365
TI  - Intratympanic gentamicin therapy for meniere's disease.

PMID- 23119366
TI  - Sudden sensorineural hearing loss: An update.
AB  - For many otolaryngologists the management of acute sensorineural hearing loss is
      an intuitive exercise. The ideas that govern a practice is as important as
      treating the patients and preventing progression of the disease; this has evolved
      by retrospective, anecdotal reports and clinical experience rather than through
      prospective research. To evaluate the current literature on management of such
      sensorineural hearing loss, a medline search of the topic was carried out and
      evidence based on recent articles were analysed. The review article discusses the
      current opinion on the subject including investigations and suggests a management
      protocol for idiopathic cases.

PMID- 23119367
TI  - Thesis as a part of ms/md training programme-where do we stand?

PMID- 23119368
TI  - Annual conference of AOI- it's past and present.

PMID- 23119369
TI  - Rhinology: past-present-future.

PMID- 23119370
TI  - Mucociliary clearance in chronic sinusitis.
AB  - Mucociliary clearance is an important defence mechanism of upper and lower
      respiratory tracts. Any disturbance in the mechanism leads to stagnation of
      secretions and secondary infection with prolonged mucociliary clearance time. The
      present study was undertaken to establish normal mucociliary clearance time in
      our region and to evaluate its diagnostic and prognostic potential in chronic
      sinusitis of variable duration with and without obstructive diseases.A simple
      Saccharine test was done in twenty healthy individuals and fifty patients
      suffering from Chronic Sinusitis, before and after treatment, to know the effect
      of disease on mucociliary clearance.The normal mucociliary clearance time in our
      region is 6.99 +/- 0.26 with S.D. 1.15 and significant change in mucociliary
      clearance occurs in Chronic Sinusitis.

PMID- 23119371
TI  - Juvenile angiofibroma: review of a case series and role of embolization.
AB  - Here 15 cases of advanced Juvenile angiofibroma are presented. Advantages of wide
      tumour exposure and preoperative embolization are discussed.

PMID- 23119374
TI  - Esthesioneuroblastoma.

PMID- 23119372
TI  - Rhinocerebral invasive aspergillosis.
AB  - Here we present 10 cases of rhinocerebral aspergillosis. In this study we
      included only invasive type of cases. In 4 of these disease had extended into the
      brain parenchyma and in remaining cases diseases had extended intracranially but
      dura was not invaded. Details about the operative procedure and followup is
      presented. Till date only 3 of these cases are surviving.

PMID- 23119375
TI  - Importance of pre-operative embolization in the surgery of nasopharyngeal
      angiofibroma.
AB  - Juvenile Nasopharyngeal Angiofibroma are rare vasoformative(1) neoplasms of the
      Nasopharynx. Due to innocuous nature of their presenting symptoms, the tumour
      frequently has extranasopharyngeal extensions at the time of initial
      diagnosis.The advances in radiographic CT techniques(2) and pre-operative
      embolization(3) have reduced the mortality and morbidity to a great extent. We
      analysed nine cases of angiofibroma with and without embolization and concluded
      that preoperative embolization reduces intraoperative blood loss considerably
      giving excellent surgical clearance of the tumour mass with minimal risk of
      recurrence.

PMID- 23119376
TI  - Sino-nasal carcinoma with multiple cutaneous secondaries.
AB  - An unusual case of an Anaplastic carcinoma of sino-nasal tract (maxillo-ethunoid
      angle) with multiple secondary deposits in the skin without lymph nodes and other
      known distant metastatic sites involvement is being reported.

PMID- 23119377
TI  - Aspergillosis of the maxillary sinus.
AB  - A rare cse of aspergillosis of the maxillary sinus is reported. Surgical excision
      including the lining of the infected sinus is the preferred method of treatment.
      Antifungal therapy does not seem to affect the prognosis of this disease.

PMID- 23119378
TI  - The protocol for the diagnosis of obstructive sleep apnea syndrome.
AB  - Our understanding of the nature and the sequence of upper airway obstruction has
      evolved gradually but considerably. This obstruction, occurring repeatedly in
      sleep alongwith daytime sleepiness is called Sleep Apnea Syndrome. Narrowing or
      closures may occur at one or more sites in an unstable upper airway. The upper
      airway size is determined by soft-tissue and skeletal factors, that are also
      major determinants of upper airway patency during sleep. The presence of certain
      physical characteristics should strengthen the surgeons suspicion of some
      dysfunction during sleep. There are various methods of identifying the physical
      attributes in patient of Sleep Apnea. The measurement of all the characters plus
      the sleep study, helps the surgeon eventually to select the site needing
      immediate treatment. This will not only straighten the upper airway but also
      prevent any re-occurrences, which is very common if the patient is not properly
      evaluated. Great stress should be laid on presurgical protocol, an alternative
      for more appropriate diagnosis and treatment.

PMID- 23119379
TI  - Malignant fibrous histiocytoma of maxilla - a report of five cases and review of
      literature.
AB  - Malignant fibrous histiocytoma of the maxilla is a rare malignant tumor of the
      bone. Affection of maxilla does not occur very commonly. In this report five
      cases of fibrous histiocytoma have been presented along with a review of
      literature.

PMID- 23119380
TI  - Nasal mucous ciliary clearance and olfaction in atrophic rhinitis.
AB  - Nasal mucocilliary Clearacne (NMCC) was studied in 75 cases of atrophic rhinitis
      and results were compared with 35 healthy controls using Anderson's method.
      Olfaction in atrophic rhinitis decreases but its extent has not been studied
      earlier. We have tried to quantify olfaction. This was normal in 10.6%, mild
      hyposmia was seen in 30%, severe in 23.33% and anosmia was present in 36%.

PMID- 23119382
TI  - Epidermoid cyst extending to nasal septum.

PMID- 23119381
TI  - Eustachian tube in atrophic rhinitis.
AB  - Atropic Rhinitis is a chronic non-specific disease characterised by atrophy of
      mucosa and turbinate bones. Maxillary antrum may sometimes be involved as result
      of primary disease or at time secondary to mucosal pathology or crusting.
      Extension of disease involving the eustachian tube is uncertain. In the present
      study, endoscopy of the nasopharynx was performed in 20 patients with atrophic
      rhinitis to find out the type, nature and site of lesion at the orifice of the
      eustachian tube. The lesion was found in seven cases (35%) involving the
      eustachian tube. The lesion occurs in form of atrophic changes with crusting
      granuloma and thick mucoid area. Endoscopy is also found to be therepeutic value
      in removing the thick discharge crust etc. at the orifice of eustachian tube to
      prevent the otological complications.

PMID- 23119383
TI  - Giant frontoethmoid mucoceles - what is the surgical choice.

PMID- 23119384
TI  - A rare case of primary Ewings sarcoma of the nasal bone.
AB  - Primary Ewing's sarcoma of the nasal bone has not been previously described. This
      case presented as a mass in the left ala of the nose in a five year old female
      child. The clinical, radiological, microscopic features are described and a
      review of literature is presented. The case was treated with neoadjuvant
      chemotherapy and local electron beam radiation therapy. The child was free of
      disease when she reported for follow up in July 1997. Although wide excision is
      part of the treatment approach in Ewing's sarcoma, in sites where surgery is not
      suitable local radiotherapy and chemotherapy adequately controls primary disease.

PMID- 23119385
TI  - Pleomorphic adenoma of nasal cavity.

PMID- 23119386
TI  - Inverted papilloma - an analysis of 30 cases.
AB  - Clinical, radiological and surgical details of 30 patients of inverted papilloma
      treated between the years 1990-1995 were analysed. Inverted papilloma is a benign
      but locally aggressive tumour. Unilateral nasal obstruction with or without
      bleeding was the commonest presenting feature. More than half of the patients
      gave history of previous surgery. CT scan is a good modality to know the exact
      extent of the lesion and plan surgery. Radical surgery was done in all patients.
      We had recurrence in 1 patient (3.3%) and two patients had carcinomatous change
      (6.6%). The results are presented with brief review of literature.

PMID- 23119387
TI  - Pleomorphic adenoma of the nasal septum.
AB  - Pleomorphic adenoma of the nasal septum is a rare finding in ENT practice. We
      present such a case and discuss the relevant and peculiar histological findings,
      together with a brief description of the management and potential complications
      of such tumours.

PMID- 23119388
TI  - Endoscopic intranasal dacryocystorhinostomy.

PMID- 23119389
TI  - Benign fibrous histiocytoma of the maxillary sinus.
AB  - Fibrous Histiocytoma is an uncommon neoplasm of the Head and Neck region and
      quite rare in the paranasal sinuses. We are reporting a case of Benign Fibrous
      Histiocytoma in the Maxillary sinus from the Department of Otorhinolaryngology of
      Bolani Hospital, Bolani with a description of clinical and histological features
      of the neoplasm.

PMID- 23119390
TI  - Malignant fibrous histiocytoma of ethmoid sinus.
AB  - Malignant Fibrous Histiocytoma (MFH) is a rare tumour to involve ethmoid sinuses.
      So far only 7 cases have been reported in the literature to our best of
      knowledge. The disease predominantly affected younger people with no significant
      sex prediliction. The aggressive behaviour of the tumour clinically is an
      important parameter to clinch the malignant nature of the disease. Wide surgical
      resection is the accepted method of treatment. Local recurrences are frequent and
      distant metastasis are not known from ethmoid sinus.

PMID- 23119391
TI  - Antrochoanal polyp-a cause of obstructive sleep apnoea in children.
AB  - Obstructive sleep apnoea syndrome is a well established entity which has received
      much attention in the recent past. In children the commonest cause of sleep
      apnoea is adenotonsillar hypertrophy. We report two cases of antrochoanal polyp
      in children who presented with symptoms consistent with sleep apnoea.
      Preoperative polysomnography was performed in these cases which confirmed the
      diagnosis of sleep apnoea. Under general anaesthesia both children underwent
      polypectomy with middle meatal antrostomy Post operatively the patients were put
      on steroid nasal spray for 2 weeks. Repeat polysomnograpy performed four weeks
      following surgery revealed reversal ot disturbed sleep patterns.

PMID- 23119392
TI  - Rhinoplasty in cleft lip/palate deformity.

PMID- 23119393
TI  - Endoscopic sphenopalatine ganglion block for pain relief.
AB  - The anaesthetic effect of the sphenopalatine (SPG) block has been well utilized
      for intranasal topical anaesthesia but the analgesic efficacy of (SPG) block,
      though well documented in literature, has not been put into practice. The methods
      available for SPG block till date were blind as they do not visualize the
      foramen. Nasal endoscopies have been used to visualize the foramen for an
      effective block. The authors present their experience with the endoscopic
      sphenopalatine ganglion block for pain relief in head and neck malignancies and
      neuralgias.

PMID- 23119395
TI  - Readers' forum: 12.

PMID- 23119394
TI  - Wedge Resection of the Middle Turbinate-An Adjunct to Functional Endoscopic Sinus
      Surgery (FESS).
AB  - A simple technique of wedge resection of the anterior part of the middle
      turbinate allows a better access to the Osteo meatal complex (OMC) during FESS
      procedure. In post-operative period it facilitates proper ethmoid cavity care,
      mandatory to the success of the endoscopic sinus surgery. The technique keeps the
      middle turbinate away from the lateral wall of the nose and helps reducing the
      synechia formations. It also exteriorises the apparent and occult pneumatised
      middle turbinate. It is a simple and safe procedure to perform with minimal
      trauma to the middle turbinate without complications attributable to the
      technique. During functional endoscopic sinus surgery this technique affords
      improved exposure to the OMC in patients with high deviated septum, narrow nasal
      vault, a large concha bullosa and paradoxical turbinate.

PMID- 23119396
TI  - Notable men in ent.

PMID- 23119397
TI  - Otorhinolaryngological studies in diabetics.
AB  - A total of 50 patients with diabetes mellitus were the subject matter of this
      study. Of these, 13 patients had diabetic neuropathy on clinical evaluation.
      Amongst the group of patients without diabetic neuropathy, 64.86% had
      sensorineural hearing loss and 21.6% patients had conductive deafness as compared
      to patients with diabetic neuropathy having sensorineural hearing loss in 69.2%
      and conductive deafness in 23% cases. The hearing threshold were found to be
      within normal limits in deabetics with or without neuropathy at lower frequencies
      but it was significantly incressed at higher frequencies (4000 Hz and 8000 Hz) in
      patients with diabetic neuropathy when compared with diabetic patients without
      neuropathy. The hearing threshold were increased at higher frequencies in
      uncontrolled diabetics. This was significant when compared with diabetics with
      normal fasting plasma glucose. The values of these tests as diagnostic and
      prognostic tools presently remains of no avail. However, it is hoped that with
      better precision and sophistication they may be utilised to detect finer
      sensorineural loss in diabetics, much before the development of long term
      complication inflicting the nervous system. This study also underlies the
      importance of looking for the hearing defects in diabetics which may be
      insignificant to the patient in face of apprehension for the disease itself.

PMID- 23119398
TI  - Vaccination in India.

PMID- 23119399
TI  - Original article: Study of congenital anomalies of pinna and the ecological
      influence on it's development.
AB  - Pinna is present in mammals only and not found in any other living species.
      Various congenital anomalies of Human pinna often mimic the appearance of normal
      pinna of many mammals of lower order. Ecology has been observed to play a role in
      the development of pinna. Anomalous pinna though frustrating for both patients
      and clinicians, are mostly amenable to treatment.

PMID- 23119400
TI  - Role of computed tomography in unsafe chronic suppurative otitis media.
AB  - Thirty Patients of Unsafe chronic suppurative otitis media were subjected to pre
      operative CT scanning followed by surgical exploration of the middle ear and
      mastoid, and their scans were compared with the peroperative data. High
      resolution CT scanning has been advocated for evaluation of unsafe chronic
      suppurative otitis media as it is capable of delineating detail required to
      detect Labyrinthine fistulae, Facial canal erosion, Sinus and Dural plate erosion
      and Ossicular integrity. Our results showed CT scan to be highly sensitive for
      soft tissue density mass in the middle ear and mastoid. Dural plate exposure,
      Sinus plate erosion, Facial canal and Stapes integrity, moderately sensitive for
      Malleus and Incus integrity and least sensitive for Lateral canal fistulae. Both
      Axial and Coronal scans were done as many important structures are best seen in
      only one of these planes. The principal merit of CT scan of the Tomporal bone
      lies in its inherent ability to depict pathology which is not clinically evident.

PMID- 23119401
TI  - A study of prevalence of cholesteatoma in complications of suppurative otitis
      media.
AB  - Complications of suppurative otitis media are common in developing world.
      Cholesteatoma has been implicated as the causative factor. We studied 76 cases of
      suppurative otitis media presented with complica tions and found that only 64%
      cases had cholesteatoma. Granulation were present in most of the cases of
      intracranial complications (16.68%).

PMID- 23119402
TI  - Hearing loss in rural population : the etiology.
AB  - Out of the five sensations, hearing is a major one. The gross impairment of
      hearing especially in the children lead to lack of development of speech and
      makes the person grossly handicapped. This study consisting of 758 cases from
      rural area having hearing impairment, was aimed to findout the various
      aetiological factors resulting in hearing loss. 62.2% of cases belonged to 0-20
      years age group. Otitis media (57.25%) was the commonest aetiological factor.
      Conductive hearing loss was the commonest type of hearing loss in otitis media.
      86.17% cases of otitis media were in age group 0-20 years.

PMID- 23119404
TI  - Embryonal rhabdomyosarcoma of the mastoid in an infant.
AB  - A case of embryonal rhabdomyosarcoma of the mastoid in a six weeks old infant is
      reported because of rarity and unusually early onset of the disease.

PMID- 23119403
TI  - Current opinion in the management in acute otitis media.
AB  - The management of Acute otitis media has been a subject of controversy. This
      paper discusses the the current opinion on the subject including a review of
      recent literature. The use and choice of antibiotics reflects the wide variation
      in opinion for both first line and second-line therapy. The role of
      tympanocentesis and prophylactic treatment is discussed. The introduction of
      vaccines holds new promise on the prevention of Acute otitis media. Factors
      affecting outcome influence the management plan especially in recurrent cases,
      high risk groups and treatment failures.

PMID- 23119405
TI  - Malignancies of the ear:-unusual presentations.
AB  - Two unusual cases of squamous cell carcinoma of ear.One presenting as brain
      abscess.Other one presenting as recurrent polyp of the ear.-case of
      Rhabdomyosarcoma presenting as mastoid abscess in a one year old male child with
      VIth & VIIth cranial nerve palsy.A case of squamous cell carcinoma of the year
      having recurrent post operative haemorrhage treated by external carotid artery
      ligation followed by radiotherapy.

PMID- 23119406
TI  - Facial nerve schwannoma.
AB  - An uncommon case of bilobed facial nerve schwannoma and its management is
      presented.

PMID- 23119407
TI  - Pseudocyst of the auricle-a new method of treatment.
AB  - Pseudocyst of the auricle is a rare condition and is hardly encountered in
      routine ENT practice. There have been only about 200 of these cases reported in
      world literature. The etiology remains obscure and the treatment modalities
      uncertain. The authors present their series of 15 cases and review the available
      literature on this condition. A new and completely successful method of treatment
      is also presented.

PMID- 23119409
TI  - Fungal and bacterial flora of chronic suppurative otitis media in amritsar
      (punjab).
AB  - Ear discharge specimens from 182 clinically diagnosed cases of chronic
      suppurative otitis media were cultured for isolation of fungi and bacteria.
      Positive fungal cultures were obtained in 13.7 %; present alone in 7.6% and
      incombination with various bacteria in 6.1%. Bacteria alone were present in 60.4%
      cases. The fungal isolates were candida albicans (60%) and Aspergillus (40%).
      Bacterial isolates showed the predominence of pseudomonas aeriginosa (44.8%)
      followed by Staphylococcus aureus (20.4%). Newer antibiotics like Cefotaxime,
      Gentamicin and Ciprofloxacin were found to be more effective against all the gram
      positive and negative isolates.

PMID- 23119410
TI  - Primary diphtheritic otitis media and mastoiditis.
AB  - Diphtheritic infection of the ear is very rare. We report here a case of Primary
      Diphtheritic Otitis Media with a brief review of the literature.

PMID- 23119411
TI  - Plester's Angled Prosthesis for Ossicular Chain Reconstruction.
AB  - Reconstruction of a defect of the long process of the incus by means of bone
      chips, cartilage grafts or other material do not give satisfactory long term
      results. Plester developed therefore an angled prosthesis to reconstruct the
      defect. It consists of a cross-slit gold bell which is connected with a double
      band titanium cuff by a tiny gold wire. The prosthesis crimped on the stamp of
      the long process with open tatanium bands, the bell is kept overthe head of the
      stapes, The authors have inserted 81 angled prosthesis. In 63 cases, the post
      operative conductive hearing loss amounted to 15 dB on an average.

PMID- 23119412
TI  - CO2 Laser Stapedotomy-Our Experience-A Preliminary Report.
AB  - Laser Stapedotomy is now the routine surgical procedure performed for
      otosclerosis in numerous centres in the world. The authors describe their
      preliminary experiences with the use of the CO2 laser for stapedotomy. 10
      patients operated in a period of 3 months in 1996 have been included in this
      study. The surgical technique is simple and easy to perform. Preliminary results
      seem to indicate lesser post op morbidity, and better hearing results in these
      patients as compared to those cases operated by conventional techniques.

PMID- 23119413
TI  - Telescopic Examination of the mastoid Cavity.
AB  - Otoendoscopy enables viewing of different angles of the tympanomastoid area and
      approach to them for better prognosis. A comparative study of post-operative
      mastoid cavities has been done using the Hopkin's rod telescope, Otoscope and
      microscope. Various procedures have also been done successfully on the mastoid
      cavity using the telescope on an outdoor basis.

PMID- 23119414
TI  - An alternate approach to the mastoid antrum.
AB  - An alternate approach to the mastoid antrum for acellular mastoid is presented.

PMID- 23119415
TI  - How I Perceive it? "Partinnitus": (Proposed New nomenclature for otospongiotic
      tinnitus).

PMID- 23119416
TI  - Readers' forum-13.

PMID- 23119418
TI  - Words of wisdom.

PMID- 23119417
TI  - Co-amoxyclav in ENT infections.

PMID- 23119419
TI  - Journal scan.

PMID- 23119420
TI  - Notable men in ENT.

PMID- 23119421
TI  - Letter to the editor.

PMID- 23119422
TI  - Tobacco related diseases-can we stop it?

PMID- 23119423
TI  - Recent advances in the use of lasers in otolaryngology.
AB  - The laser (Light Amplification by Stimulated Emission of Radiation) has been used
      in Otolaryngology for over 20 years and is by now an accepted part of the
      armamentarium. A tremendous amount of work is being done in refining existing
      techniques and developing new ones, and this review discusses some of the recent
      advances.

PMID- 23119424
TI  - Studies on the blood nicotine level in the oral and oropharyngeal cancers of
      habitual tobacco users.

PMID- 23119425
TI  - Human papillomaviruses in hypopharyngeal squamous cell carcinoma.
AB  - Human papillomaviruses (HPV) have been detected in squamous cell carcinoma (SCC)
      of the aerodigestive tract with varying frequency of 10%-100% mainly due to
      detection methods and primer pairs used. Polymerase chain reaction (PCR) is the
      most sensitive and Southern blot hybridization (SBH) the most specific detection
      method of HPV DNA. Both methods achieve the most reliable results. 22 SCC DNA
      samples of the hypopharynx were analyzed by type specific and consensus primer
      PCR and Southern blot analysis. HPV was detected in 5/22 (22.6%) hypopharyngeal
      SCC specimens. HPV 18 and HPV 45 were identified in one case each. An HPV
      prevalence of 23% is a realistic approximation in hypopharyngeal SCC. The high
      rate of HPV positive only detected by non type specific detection methods
      indicates the presence of previously undescribed HPV types.

PMID- 23119426
TI  - Woodman's operation for bilateral vocal cords paralysis-our experience.
AB  - Woodman's External Arytenoidectomy technique is described and evaluated in 6
      patients. This operation have many desirable features, including extra laryngeal
      approach and control over degree of cord lateralization. The disadvantage being
      limited exposure of arytenoid cartilage. The effects of the laterofixation on
      Breathing and Vocie were analysed in all cases.6 patients have been operated
      using Woodman's method and in all cases breathing was improved and the influence
      on the voice was moderate and adjustable. We suggest this method to be the first
      treatment of choice in patients suffering from Bilateral Vocal Cord Paralysis
      (BVCP).

PMID- 23119427
TI  - A clinicopathological study of the pre-malignant conditions of oral cavity.
AB  - The pre-malignant conditions of the oral cavity are those which has got a
      potentiality to turn malignant in its due course if left untreated. It was only
      in 1967 when an international reference center for the study of Oral Pre
      cancerous Lesion was established by the World Health Organization. The main
      importance was given to Leukoplakia. The conditions considered as premalignant
      are Leukoplakia, Lichen planus, Oral submucous fibrosis and erythroplakia. There
      lesions has got a very close association with the local habits practised by the
      people. So in this paper this point has been highlighted.The study has included
      the patient within a time span of one year from 5th April, '94 to 4th April '95.
      Though the number of the patients is not much but we find it sufficient enough to
      bring awareness on these potentially dangerous lesion thereby preventing oral
      cancers.

PMID- 23119428
TI  - Cysts of the larynx : A clinicopathologic study of nine cases.
AB  - In this only report from India, nine patients with laryngeal cysts have been
      diagnosed in the 24 year period from Jan 1971 through Jan 1996 representing 0.01
      % of 1,05,279 general biopsies and 1.16% of 774 laryngeal biopsies received. The
      patients were mainly male with a mean age of 48.87 years. They presented with
      laryngeal obstructive symptoms. Six of the patients were chronic cigarette
      smokers. None had history of voice abuse. Laryngoscopic examination showed
      solitary cysts situated in the supraglottic region in seven cases and in the true
      vocal cords in two. Using modified DeSanto's classification of laryngeal cysts
      putforth by Newman et al (1984), four were ductal, three saccular and one of
      tonsillar type. However, one of the cysts having features of an epidermoid cyst
      could not fit into the classification. The major proposed classifications of
      laryngeal cysts which are in practice have resulted in much confusion for both
      clinicians and pathologists and these have been studied in depth and their
      implications discussed here.

PMID- 23119429
TI  - A study of incidence and pattern of nodal metastases in patients of
      otorhinolaryngological malignancies.
AB  - Malignancies of otorhinolaryngology are of utmost importance because of a high
      incidence and early involvement of lymph nodes. It has been experienced and
      suggested by various authors that topographical distributions of metastatic lymph
      node is important not only in patients with undiagnosed primary but also as a
      significant prognostic factor in cases of known primaries. This is a prospective
      study based on 200 previously untreated patients of otorhinolaryngological
      malignancies with clinically suspected metastatic cervical nodes observed during
      one year period. The detailed study of pattern of lymph node involvement arid its
      correlation with tumour (T) and nodal (N) stage was studied. The level of lymph
      node involvement and N-stage is related with stage site and histopathology of the
      primary site. The more advanced the T-stage the more advanced the nodal stage.

PMID- 23119430
TI  - Community based oral precancerous lesions/conditions : an analysis of associated
      factors.
AB  - Despite overwhelming evidence documenting the carcinogenic effects of tobacco,
      the per capita consumption of tobacco is alarmingly increasing. A base line
      survey has been conducted in 4 villages in central India. Tobacco users were
      identified and interviewed. The oral mucosa was examined for the clinical
      lesions. Odds ratios for the oral precancerous lesions/conditions were assessed
      utilising the woolfs method. Out of the 3088 rural pupulation examined, 21.6%
      were found to be habituated to tobacco. Out of 668 tobacco users, 492 (73.6%)
      were chewing tobacco with lime. Premalignant lesions (leukoplakia) was observed
      in 111 cases. Premalignant condition (oral sub mucous fibrosis) was found in 12
      cases. Out of 138 adult tobacco chewers who began the habit at or before the age
      of 14 years, 68.8% chewed 10 grams or more of tobacco per day compared with 42.8%
      (51 out of 119) of those who started the habit when they were 25 years or older
      (P< 0.001).

PMID- 23119431
TI  - Lymphangioma circumscriptum of the skin and tongue associated with cystic
      hygroma.
AB  - A 25 year-old-woman with lymphangioma circumscriptum of the skin and tongue
      associated with cystic hygroma is reported for its rarity and unique
      presentation.

PMID- 23119432
TI  - Liposarcoma of the larynx treated with radiotherapy.
AB  - Liposarcoma of the larynx is an extremely rare malignancy. Only 18 cases have
      been reported in the literature. We herein report the first case of primary
      liposarcoma of supra-glottic larynx in a 53-years old male patient successfully
      treated with radiotherapy in August-September 1992. He currently remains free of
      the disease 4.5 years since the initial diagnosis.

PMID- 23119433
TI  - Lingual thyroid.
AB  - Lingual thyroid is an uncommon entity (Incidence: 1 per 10,000 individuals). The
      first case was noted in 1869 by Hickmann. In 1972, a total number of 373 cases
      were collected from the world literature. Because of the rarity and the
      suprahyoid approach of Operation Choosen, this case is reported.

PMID- 23119434
TI  - Retropharyngeal abscess following accidental throttling.
AB  - Acute retropharyngeal abscess is common in infants and small children due to
      supuration of retropharyngeal lymph nodes. It is also not uncommon in adults due
      to injury of posterior pharyngeal wall by sharp object, foreign bodies and
      instrumentation. But acute retropharyngeal abscess following accidental
      throttling is reported for unusual etiology.In present study a case of accidental
      throttling followed by acute retropharyngeal abscess is being reported due to
      rareness.

PMID- 23119435
TI  - Overlooked impacted dentures and their unusual complications.
AB  - Two interesting and unusual cases of overlooked impacted dentures in oesophagus,
      one for 3 months and the other for 2 years are reported. We also report the
      complications of Bilateral Recurrent Laryngeal Nerve Paralysis and Oesophageal
      Diverticuli due to prolonged obstruction by denture.

PMID- 23119436
TI  - Clinico microbiological evaluation of surface and core microflora in chronic
      tonsillitis.
AB  - A total of 100 patients with chronic tonsillitis were selected for this study.
      Specimens collected immediately before surgery and the operated specimen of
      tonsils were subjected to appropriate microbiological techniques. The commonest
      isolate on the surface was Streptococcus pneumoniae and in the core group a
      streptococcus. The largest group was the one in which surface and core pathogens
      were the same. At the same time it is interesting to note that surface culture
      was misleading as to the presence or absence of core pathogens in 32% of the
      study group. The core only was pathogenic in 12% and the group which isolated a
      different pathogen on the surface and core was 20%. It is evident that in a
      significant group of patients surface cultures were not useful in predicting core
      pathogens.

PMID- 23119437
TI  - Tuberculosis of tongue.
AB  - Oral lesions of tuberculosis are rare and when present they are usually secondary
      to pulmonary tuberculosis. Persistent painful oral ulcer may be the only symptom
      for which the patient seeks advice. In the absence of clinical features of any
      systemic disease, these lesions may be misdiagnosed. Histopathological
      examination in such cases must be performed so as not to miss some rare
      conditions.

PMID- 23119438
TI  - Benign neoplasms of the tonsil.
AB  - Eight rare cases of benign neoplasms of tonsil treated satisfactorily in last 10
      years with varied symptomatology are included in this study.

PMID- 23119439
TI  - Unusual cause of dysphagia.
AB  - A case report of Cervical Hyperostoses or Forestiers disease causing dysphagia
      and dysphonia is presented.

PMID- 23119440
TI  - Cold nodule thyroid - A 5 year retrospective study.
AB  - FNAC and histopathological reports of 50 patients with cold nodule thyroid who
      underwent surgery during the last 5 years were analysed. FNAC showed malignancy
      in 12% of cases whereas histopathological examination in 16% of cases. In this
      study an attempt has been made to find out the role of frozen section in cold
      nodule thyroid.

PMID- 23119441
TI  - An unusual case of solitary scleroma of cheek.
AB  - Scleroma is a disease of unwashed and occurs in people living in poor unhygienic
      conditions. Commonly it involves respiratory tract. We encountered a case of
      scleroma over cheek presenting as a solitary nodule without any sign of nasal
      scleroma.

PMID- 23119442
TI  - External laryngocele.
AB  - Laryngocele is an extremely rare condition. A case of external laryngocele is
      being reported along with a brief review on its pathogenesis, clinical
      presentation and management.

PMID- 23119443
TI  - Benign fibrous histiocytoma of the upper end of oesophagus.
AB  - Benign fibrous histiocytoma of the upper end of the Oesophagus in our knowledge
      has not been reported in the literature hence interesting to report. Sudden
      popping out of the pedunculated mass from upper end of the Oesophagus into the
      laryngopharynx with irrucdation after a cold drink giving rise to almost total
      dysphagia in a young, obese, female with hypothyroidism and hypertension is
      described here.

PMID- 23119444
TI  - Synovial sarcoma of the larynx.
AB  - A 23 years old male presented with a soft cystic mass in the left paralaryngeal
      space since 3 months. Indirect laryngoscopy revealed a bulging of the left
      lateral pharyngeal wall. Histopathologic al examination of the biopsy proved it
      to be a synovial sarcoma. The case is the seventh case reported in literature.

PMID- 23119445
TI  - Cordotomy-how I do it?

PMID- 23119446
TI  - Readers' forum : 14.

PMID- 23119447
TI  - Azelastine.

PMID- 23119449
TI  - A possible role of helicobacter pylori infection in the etiology of chronic
      laryngitis.

PMID- 23119448
TI  - Words of wisdom - II.

PMID- 23119450
TI  - Self heating laryngeal mirror.

PMID- 23119451
TI  - Your image is always in our heart.

PMID- 23119452
TI  - Oncogens in ENT and head and neck - a review.
AB  - With the exploration of new horizons in the frontiers of genetic linkage with
      head and neck cancer by advanced molecular biological technique it may be
      possible to know the various steps involved in the cancer development and new
      prognostic markers for not only predicting prognosis but also progression and
      predisposition including routine diagnostic tests for mutantgenes for a better
      diagnosis and treatment of squamous cell cancers of head and neck. Various
      oncogens and their products so far identified are ras, myc, c-erb, Bl, PRAD-.l,
      int-2, hst-1 and p 53 etc with lirikage to head and neck malignancy. The HLA gene
      association is the most convincing evidence for the role of genetics in the
      aetiology of nasopharyngeal cancer. EGFR looks to be a promising prognostic
      indicator as its interaction with the polypeptide epidermal growth factor
      stimulates proliferation of target cells.

PMID- 23119453
TI  - Use of dynamic compression plates in rigid internal fixation for Mandibular
      fractures.
AB  - Vehicular accidents and Urban violence continues to be a major source of
      faciomaxillary injuries, Mandible being more commonly injured than other facial
      bones. A series of seventy five patients surgically treated for facial fractures
      between Jan '92 and Dec. '94 was reviewed. Of these, 51 had mandibular fractures
      at different sites like Angle and Body, Body and/or Symphysis and Ascen-ding
      Ramus. All these patients were treated with rigid internal fixation using Dynamic
      Compression Plate on A. O principle. It provided complete anatomical reduction
      and stimulated bone healing and full range of movement. It decreases morbidity
      and Hows better control of patient's nutrional status. Patients can return to
      normal routine work after 8 to 10 days.

PMID- 23119454
TI  - Effect of radiation on oropharyngeal flora in patients of head and neck cancer.
AB  - In the Present study 124 cases of head and heck cancers subjected to radiation
      therapy were studied and the change in oropharyngeal flora with the radiation
      therapy noted. 50 cases for comparison with no ENT complaints were taken control.
      The oropharyngeal flora in the control cases was established as the normal flora.
      Any other floral constituent was considered to be abnormal oropharyngeal flora.
      It was found that with radiation there was a statistically significant increase
      in several constituents of normal as well as abnormal oropharyngeal flora. This
      increase could be the predisposing factor for post radiation infections
      especially in post operative patients. Oropharyngeal swabs were sent before,
      during and after radiation therapy for detailed bacterial and mycotic flora smear
      and culture examinations.

PMID- 23119455
TI  - Anterior skull base surgery- our experience.
AB  - Anterior skull base surgery is now an accepted treatment modality for many
      lesions involving the anterior skull base including the pituitory region. This
      paper deals with a fifteen year experience over various approaches to the
      anterior skull base, and thereby trying to rationalize the appropriate approach
      for the tumours in different anatomical situations. Relevant literature has also
      been reviewed.

PMID- 23119456
TI  - Comparative evaluation of chemoimmunoradiotherapy and chemoradiotherapy in the
      management of advanced head and neck cancer.
AB  - 50 patients of advanced squamous cell carcinoma of the head and neck were
      randomised cither to receive chemotherapy followed by radiation therapy or
      chemoimmunotherapy followed by radiotherapy. In the chemoimmunotherapy arm, the
      patients received recombinant interferon alpha 2b 3 M.U. subcutaneously, thrice a
      week on alterante days for 5 weeks from Day 1, Cisplatinum 70 mg/ m(2) on Day 1
      and 21, and 5 - flurouracil 1000mg/m(2) on Day 1, 2, 3 and Day 21, 22, 23,
      followed by from Dav 36, radiotherapy'by Co bait 60 to a tumour dose of 65 Gy in
      30 # over 6 weeks. In the control arm, patiens received Cisplatitnum 70 mg/ m(2)
      on Day 1 and Day 21, 5 flurouracil 1000 mg/ m(2) on Dav 1, 2, 3 and Day 21, 22,
      23 followed by radiotherapy by Cobalt 60 to a tumour dose of 65 Gy in 30 # over 6
      weeks from Day 36. Only Grade II and III toxicity was observed in the two arms
      which were manageable Patients treated with chemoimmunotherapy followed by
      radiotherapy showed 60% complete response, 20% partial response and 12% no
      change/ progressive disease; while the patients on the control arm treated with
      chemotherapy and radiotherapy showed 12% complete response 44% Partial response
      and 32% no change" progressive disease. This trial concludes that
      chemoimmunotherapy followed by radiotherapy is an excellent alternative
      therapeutic strategy for the management of advanced head and neck cancers with
      manageable toxicity.

PMID- 23119457
TI  - Surgery in early cancer of the oral tongue (Tl-2). Wide excision versus
      hemiglossectomy.
AB  - Cancer of the oral tongue is a common disease. Thirty five (35%) percent of
      patients seen at our hospital are in Stages I&II. The choice of surgical
      treatment is a wide excision of the lesion (WE) or a hemiglossectomy (HG). This
      study was carried out to compare the local recu-rrences and survival in patients
      undergoing either a WE or HG for early cancer of the tongue. One hundred and
      twenty six (126) patients were evaluated, 40 underwent a WE and 86 HG. The local
      recurrence was higher in the WE group, 25% compared with 9% in the HG group;
      which is statistically significant (p=0.02). This was also seen in the Tl
      subgroup (p=0.003). Survival were better in the HG group (p=0.005), which was
      also seen for the Tl subgroup (p=0.004). Our study demonstrates that there is a
      lower incidence of local recurrences following a hemiglossectomy for Tl-2 tumours
      of the oral tongue with improved survivals. Our recommendation is that hemi
      glossectomy should be the optimal surgery performed for early cancer of the oral
      tongue.

PMID- 23119458
TI  - Lead article: The prognostic significance of proliferating cell nuclear antigen
      (pcna) in laryngeal cancer.
AB  - Squamous cell carcinoma arising from upper aerodigestive tract carries with it a
      significant morbidity and mortality and, over the last few decades, its incidence
      has steadily increased. The management of patients requires thorough
      investigation to determine the local, regional, and distant extent of the
      disease, and treatment options include surgery, radiotherapy, chemotherapy, or
      combinations of these.Despite the large number of therapeutic and hsitopathologic
      studies in print, there is currently no morphologic or cytologic feature
      available which consistenly predicts outcome in patients with laryngeal
      carcinoma. The use of proliferating cell nuclear antigen (PCNA), a newly
      available marker of a cell's proliferative activity ( S-phase fraction), was
      evaluated in 25 cases of squamous cell carcinoma of the larynx. PCNA scores
      differed, statistically significantly as far as the localization of the lesion,
      pathological grade, clinical stage, presence of lymph node metastases and
      prognosis of the patients were concerned.These data suggest that PCNA is an
      indicator of the malignant potential of the larynx. PCNA can be used in decision
      making for treatment and assessing prognosis in carcinoma of the larynx.

PMID- 23119459
TI  - The indications and complications of pectoralis major myocutaneous flap
      reconstruction in head and neck surgery-our experience.
AB  - Most of the head and neck cancer patients in India present to the
      Otolaryngologist, Head and Neck surgeon in the advanced stages of their disease.
      Extensive resection followed by acceptable morphological & functional
      reconstruction is the goal for the surgeon. Use of the pectoralis major
      myocutaneous (PMMC) flap enables extensive ablative procedures to be carried out
      followed by immediate and reliable reconstruction. Thirty consecutive cases of
      biopsy proven squamous cell carcinoma of the head and neck region were studied.
      All underwent extensive resection of the tumour with pectoralis major
      myocutaneous flap reconstruction, with preor post-operative external irradiation.
      This study concentrates on the indications for and complications encountered with
      the use of the pectoralis major myocutaneous flap. Also included is an extensive
      review of the literature relating to the complications encountered with the use
      of this method of reconstruction.

PMID- 23119460
TI  - Incidence of occult primary-their diagnosis and surgical management.
AB  - Twenty one (16.5%) cases of Occult primary 10 males and 3 females were analysed
      out of 121 cases of secondaries in the neck regarding their diagnosis and non
      surgical management over a period of six years, from march 1990 to Feb., 1996 in
      the department of ENT and Radiotherapy of I.G.M.C. & Hospital, Shimla. Majority
      of these cases were in the age group of 50-70 years and 95% of these cases had
      squamous cell carcinoma & in one case there was adenocarcinoma. 12 (57%) of these
      patients were in N3stage. 13 patients were treated by radiotherapy, 3 by
      chemotherapy whereas remaining 5 cases absconded and therefore no treatment could
      be given to them.

PMID- 23119461
TI  - Klippel-feil syndrome-appropos of a case.
AB  - Klippel-FEIL syndrome is a congenital skeletal malformation characterised by the
      fusion of various cervical and occasionally thoracic vertebrae, leading to low
      hair line and short neck. Occasionally it is associated with hearing loss and
      Sprengel deformity with winging of scapulae. This case is being reported for its
      rarity.

PMID- 23119462
TI  - Congenital teratoid tumour of nasopharynx with cleft palate.
AB  - A case of congenital nasopharyngeal teratoid tumour presenting since birth
      projecting into oral cavity through the palatal cleft & gradually increasing in
      size thus causing breathing & feeding difficulty in a four months old female
      child is presented here for its rarity. A brief review of literature and
      management of such patients is also discussed here.

PMID- 23119463
TI  - Myxoma of maxilla.
AB  - A rare case of Myxoma of right maxilla in a 25 year female, presenting as
      bilateral nasal obstruction with destruction of the septum and maxillary antral
      bone is reported.

PMID- 23119464
TI  - A solid variant of aneurysmal bone cyst of maxilla.
AB  - A solid variant of Aneurysmal Bone cyst is very rare tumour of maxilla.
      Histopathologically it is very much similar to giant cell granuloma but the
      radiographic features can influence the pathologic interpretation.A solid variant
      of anenurysmal bone cyst has been reported in facial bones and it can involve
      several adjacent bone synchronously (3). Both giant cell granuloma and aneurysmal
      bone cyst have a propensity for recurrence variably in the 15%-26% range (5).

PMID- 23119465
TI  - Tumours of the parapharyngeal space.
AB  - A series of 14 parapharyngeal tumours has been studied with regard to their
      symptology, pre-operative evaluation and surgical management. High resolution
      computed tomography is now the best initial diagnostic study because it helps to
      determine the size and extent of the tumour, differentiate tumours of parotid and
      extraparotid origin, demonstrate degree of tumour vascularity, separate benign
      from malignant lesions, plan the surgical approach and predict prognosis.

PMID- 23119466
TI  - Fibromatosis of thyroid gland-a case report.
AB  - Fibromatosis covers a broad group of benign fibrous tissue proliferations of
      varied microscopic appearances that are intermediate in their biological
      behaviour between bengin fibrous tumour and fibrosarcoma, Extra abdominal
      fibromatosis in the neck occassionally cause serious sequellae when aggressive
      invasion of vital structure occurs. However, the principle of wide excision is
      difficult to apply in some patients because of the important organs surrounding
      the tumour. We describe a primary spindle cell tumour of thyroid that raised
      initial diagnostic problems and was eventually diagnosed as fibromatosis of
      thyroid gland.

PMID- 23119467
TI  - Peripheral ameloblastoma involving tongue-a rare case.
AB  - Peripheral ameloblastoma is a rare tumour of oral cavity. It presents as a mass
      without bony continuity. Here we report a unique case of peripheral ameloblastoma
      involving tongue, with review of relevant literature.

PMID- 23119468
TI  - Fibrous dysplasia of right upper jawuncommon presentation.
AB  - MR, 30 years, M/M had huge nasal mass for 25 years and nasal obstruction for 15
      years. On examination, a huge mass involving right side of face, nose, cheek,
      orbit and palate of 10" * 8" size was noticed. The right eye was proptosed
      eccentrically and was completely blind. Histopathological examination diagnosed
      the case to be fibrous dysplasia.

PMID- 23119469
TI  - Prochlorperazine versus cinnarizine in cases of vertigo.
AB  - Cases of vertigo comprised 1.82% of Ear, Nose & Throat out patient cases.
      Peripheral lesion as a cause of vertigo was seen in 51.12%. Meniere's disease and
      Benign Paroxysmal Positional Vertigo (BPPV) were found to be the common causes
      comprising 21.80% and 15.78% of total cases of vertigo. Central lesion as a cause
      of vertigo was seen in 48.87% of cases. Vertebre Basilar Insufficiency (VBI) was
      the commonest cause of central lesion seen in 20.30% of cases. An equal number of
      cases, selected randomly, underwent treatment with prochlorperazine +/- Head
      Balance exercises and Cinnarizine +/- Head Balance exercises. At the end of 5
      weeks of treatment there was 100% subjective improvement with prochlorperazine
      group and 97.14% in the group with cinnarizine. Side effects were noted in 34.00%
      of cases; of these 23.00% were seen in cinnarizine group and 11.00% in
      prochlorperazine. Drowsiness was the commonest side effect and was statistically
      more significant with cinnarzine group. Response to the treatment was
      significantly more in cases with vertigo of peripheral origin as compared with
      vertigo of central origin.

PMID- 23119470
TI  - Reader's Forum-15.

PMID- 23119471
TI  - Review Report of the North Eastern Branch of AOI News Bulletin Inaugural Issue,
      March 1998.

PMID- 23119472
TI  - Notable men in ent.

PMID- 23119473
TI  - Surgery of the nasal tip.
AB  - The nasal tip is considered most difficult area in entire rhinoplasty. The shape
      of the nasal tip is altered primarily by changes of lower lateral cartilages. or
      by badly performed surgery. For the assessment of the tip, its shape must be
      considered in relationship to the rest of the nose and face. Various types of tip
      deformities may be encountered. Tip may be overprojected, underprojected, bulbous
      or retruded columella may be deformed or there may be alar flaring. Tip surgery
      should be properly planned and accomplished meticulously to achieve pleasing
      results. Delivery flap technique provides excellent exposure and can deal with
      most of the tip deformities successfully.

PMID- 23119474
TI  - A wake up call for sleep disordered breathing.
AB  - OSAS is the most common and best-recognized form of SRBD. Effective treatment is
      available with CPAP being the treatment of choice, once the essential nonspecific
      measures of excluding endocrine and other treatable causes, including weight loss
      and avoiding sedative agents have been undertaken. The expense of CPAP apparatus
      and the need to use this for prolonged period may prompt some patients to
      evaluate other sub-optimal options. Surgical treatment will continue to be a
      gamble or a treatment of last resort. Whatever plan is developed, it is important
      that the patient be reassessed after six months and then by annual PSGs.The
      potential population of snorer / apneic patients is so wide and the cost of the
      proper care so high that the field is ripe for abuses. The confusion between
      symptoms of snoring and the incidence of SRBD has compounded this proliferation.
      Cut-rate care that cuts corners is often more expensive in the long run.
      Interested readers should be aware of the potential inappropriate applications of
      surgical treatment, especially LAUP, and be alerted to the best medical interests
      of their patients.

PMID- 23119475
TI  - S M R of inferior turbinate in chronic hypertrophic rhinitis.
AB  - A study was undertaken to evaluate the role of unilatcral/bilateral submucous
      resection of the inferior turbinates in fifty cases of chronic hypertrophic
      rhinitis. Patients associated with deflected nasal septum or sinus infectious
      were excluded from the study. Decongesiton of turbinates was done to exclude the
      cases with predominantly mucosal hypertrophy. Gertner (1984) plate method was
      used to asses the nasal patency preoperatively and then post-operatively at 1, 3
      and 6 months follow up. The analysis of observations made revealed SMR of
      inferior turbinate to be a very effective modality tor relieving nasal
      obstruction due to bony turbinal hypertrophy. The procedure has least
      interference with nasal mucosal integrity and functions and complications
      associated with the procedure have been found to be minimal. Histopathological
      examination of mucosa and of ostenid tissue revealed infiltration by chronic
      inflammatory cells suggesting chronic nonspecific inflammation either due to non
      specific infections and / or allergy).

PMID- 23119476
TI  - Squamous cell carcinoma of the maxillary sinus: A retrospective analysis of 36
      cases.
AB  - 36 patients with advanced squamous cell carcinomas of the maxillary sinuses
      formed the basis of this review. There were 16 T3 and 20 T4. Treatment consisted
      of radiotherapy alone in 21 cases and radiotherapy followed by systemic
      chemotherapy in 15 cases. The median survival for all analysed patients was 19
      months and the 3-year and 5-year estimated survivals were 30% and 17%. The
      respective 3-and 5-year survival probabilities were 19% and 9% for patients
      treated with radiotherapy alone and 40% and 27% for patients treated with
      radiotherapy and chemotherapy (p= 0.01). Our findings seem to suggest that the
      addititon of systemic chemotherapy to radiotherapy may imporve overall survival
      in advanced squamous cell carcinomas of the maxillary sinuses.

PMID- 23119477
TI  - Study of histopathological changes in atrophic rhinitis.
AB  - A punch biopsy from the inferior turbinate was taken in 71 consecutive cases of
      atrophic rhinitis and studied for histopahtological changes. Squamous metaplasia
      was seen in 85 percent of cases. Tunica propria showed granulation tissue (41
      percent) and chronic inflammatory cellular infiltrate (32 percent). Mucosal
      glands were decreased in 42 percent of cases and absent in 28 percent. Areas of
      dilated vessels were observed in 35 percent and decreased vascularity in 59
      percent of cases. These observations are similar to those reported by others.
      Total squamous metaplasia with keratinisation and hypertrophy was seen by us in
      one case. This has not been reported earlier.

PMID- 23119478
TI  - Cancer of the NES complex (Nasal Cavity, Ethmoid, Sphenoid Sinuses): A
      retrospective review.
AB  - During the period January 1983 to September 1993, 36 patients of Nasal Cavity,
      Ethmoid / Sphenoid Sinus Cancers were treated at Radiotherapy Department, Medical
      College. Calcutta. All were treated by irradiation alone. Local control was
      achieved in about 50% of cases at 6 weeks following completion of treatment.
      Informations with respect to tumour extension to suspected areas of spread, are
      very much necessary for accurate Radiotherapy treatment planning and for this
      reason C.T. Scan imaging is mandatory in pre-treatment work-up of NES Complex
      cancers. Precision Radiotherapy with utmost care to avoid or lessen Radiation
      dose to optic nerve, is the most suitable method of treatment for our patients.
      Stringent and prolonged follow-up necessary to know the treatment outcome as the
      tumours of NES Complex are characterised by 'delayed recurrence'.

PMID- 23119479
TI  - Giant cell reparative granuloma of maxilla.
AB  - Giant Cell Reparative Granuloma is a reparative process in mandible. A case of
      Giant Cell Reparative Granuloma of Maxilla in a 15 years old female is reported.
      Tumour is very rare in maxilla and more often is diagnosed as a giant cell
      tumour. The case is reported on account of its rarity in maxilla and dilemma in
      differentiating it from other giant cell lesions. Differentiation is only based
      on the clinical test histopathological examination.

PMID- 23119480
TI  - Antrochoanal polyp: Its pathogenesis origin and management by functional
      endonasal endoscopic surgery.

PMID- 23119481
TI  - Inverted Papilloma - An Unusual Presentation (Foreign-Body like).
AB  - Inverted papilloma of the nose is an uncommon, but, well document ed lesion of
      the mucosal lining of the nose and paranasal sinuses. The manifestation of this
      disease are usually unilateral nasal obstruction, mucopurulent nasal discharge,
      anosinia and occasional headache. It is very rare to she this condition
      presenting with dyspnoea and dysphagia due to its extension in the
      laryngopharynx. In this paper, we report a patient who presented to us with
      dyspnoea and dysphagia due to a huge papillomatous mass extending from right
      nasal cabity to the maxillary antrum laterally, posteriorly into the nasopharynx,
      interiorly into the oropharynx and the laryngopharynx.

PMID- 23119482
TI  - Benign fibrous histiocytoma of the maxillary sinus.
AB  - Fobrous Histiogytoma is an uncommon neoplasm of the Head and Neck region and
      quite rare in the paranasal sinuses. We are reporting a case of Benign Fibrous
      Histiocytoma in the Maxillary sinus from the Department of Otorhinolaryngology of
      Bolani Hospital, Bolani with a description of clinical and histological features
      of the neoplasm.

PMID- 23119483
TI  - A microbiological study of anterior nasal packs in epistaxis.
AB  - Bleeding per nose is one of the comnonest ailment encountered by each and every
      otolaryngologvst Since hemostasis is immediate concern, anterior nasal pressure
      pack is put and is usually allowed to remain for 24-72 hours. Blood soaked pack
      and raw mucosal surface are good media for bacterial multiplication resulting in
      infection including sinusitis and sometimes toxic shock syndromes.Present study
      is conducted to work out bacterial flora of anterior nasal pack and effect of
      svstemic antibiotics in controlling it. Thirty cases of epistaxis of different
      etiology were included. Out of these 26 cases were positive on culture. These
      included Staphylococcus aureus 70%,. Pseudomonas aeruginosa twenty three percent.
      Klabsiella pneumonia and proteus mirabilis 3.3%, Streptococcus and Hemolyticus
      3.3%. Details of type and duration of packing and its relation with organism
      cultured are discussed. It is concluded that the packing material should be
      soaked with antibiotics prior to use and should not be keep for more than 48
      hours. And systemic antibiotics does not have any significant on this local
      infection due to packing.

PMID- 23119484
TI  - Malignant schwannoma of the sinonasal tract.
AB  - Malignant Schwannoma of the sinonasal tract is an extremely rare tumour. So far,
      only 19 cases have been reported in the literature. We report herein a case of
      malignant schwannoma involving nasal cavity, maxillary antrum and ethmoid sinus
      in a 60-year-old male patient. The patient was treated with surgery and post
      operative radiotherapy. He currently remains free of the disease 15 months after
      the diagnosis and twelve months after completing therapy.

PMID- 23119485
TI  - A clinical study of local acriflavin in treatment of rhinoscleroma.
AB  - Rhinoscleroma is a chronic granulomatous disease which involves upper respiratory
      tract. We undertook this study to find out the antibacterial effect of local
      acriflavin on Klebsiella rhinoscleromatis, as well as the disease rhinoscleroma.
      Antibiotic effect of acriflavin was studied on one of the isolate of Klebsiella
      rhinoscleromatis using whatman No.1 filter paper disc soaked in 2% and 5%
      acriflavin solution and was found sensitive. A total of 26 cases diagnosed
      clinically and histopathologically were studied. These patients were treated
      using 1%, 2% and 5% acriflavin ointment. The cure was 33%, 67% and 100%
      respectively. Details of response to acriflavin therapy and its adverse effect
      will be discussed. It is concluded that acriflavin can be used as a good
      alternative to systemic therapy for rhinoscleroma. As it can be prepared and
      applied easily and is not a financial burden on already poor patient.

PMID- 23119486
TI  - Embryonal rhabdomyosarcoma of nasopharynx.
AB  - A rare case of Embryonal Rhabdomyosarcoma in a 5 year male child involving
      Nasopharynx with intracranial. secondaries is reported. The child presented with
      difficulty in breathing and swallowing with change of the voice and bleeding from
      nose and mouth off and on. Histopathology of the excised mass proved the
      diagnosis of RMS & CT scan showed secondaries in the left frontal & temporal to
      be of brain. In spite of the surgery and chemotherapy, the disease proved to be
      fatal within 3 months of diagnosis.

PMID- 23119487
TI  - An encephalocele replacing nose completely.
AB  - Congenital encephalocele presenting in the nasal region is extremely rare. We
      present here a case ot tncephaloce lecompletely replacing the nose of a five year
      old boy and duscuss about similar swellings in this region.

PMID- 23119488
TI  - Bilateral congenital choanal atresia presenting at age twenty two years: an
      unusual case report.
AB  - Choanal atresia is a congenital absence of communication between the nasal cavity
      and nasopharynx. Bilateral Choanal Atresia usually present immediately after
      birth and in the neonatal period. We report an unusual case who presented at the
      age of twenty two years. This case was successfully managed by a transnasal
      approach. Choanal atresia should be considered as a rare diagnostic possibility
      in any patient who presents with total nasal obstruction and persistent mouth
      breathing.

PMID- 23119489
TI  - Esthesioneuroblastoma - a rarity.
AB  - A young male presented with visual complaints of one year duration, epistaxis and
      nasal blockage of 3 months duration. He had bilateral proptosis and bitemporal
      hemianopia and a mass near the; roof of nasal cavity. Skull skiagram showed
      enlarged sella and computed tomography showed erosion of sella and a central
      mass. Partial excision of supra and parasellar tumour was done which on
      histopatho-logical examination revealed Esthesioneuroblastoma. This was followed
      by radiotherapy and CCNU twice, at 6 weeks interval. He is doing well after 1
      year and 9 months of follow up.

PMID- 23119490
TI  - Congenital teratoma of nasopharynx.

PMID- 23119491
TI  - Benign mixed tumour (pleomorphic adenoma) of the nasal cavity.

PMID- 23119493
TI  - Proboscis lateralis.

PMID- 23119492
TI  - Olfactory neuroblastoma - our experience.
AB  - The authors present six cases of olfactory neuroblastoma with or without
      intracranial extension operated on by the team headed by Otolaryngologists and
      Neurosurgeons. Data was analysed with respect lo age group, sex, presenting
      symptoms and signs, stage, and results of combined modality of treatment. The
      author's experience suggests excellent local control can be achieved by combined
      craniofacial resection followed by radiation therapy. Hence the authors recommend
      planned combined radical treatment for all the resectable lesions and routine use
      of nasal endoscope along with other conventional methods for compehensive follow
      up of all cases.

PMID- 23119495
TI  - Primary tuberculosis of nasal septum.

PMID- 23119494
TI  - Malignant nodular hidradenoma of nose.
AB  - Malignant tumours originating from the sweat glands are very rare. We report a
      case of a female with malignant nodular hidradenoma of the externa nasal pyramid.
      A brief review of literature including the histopathological aspects and
      management is presented herewith.

PMID- 23119496
TI  - Sparfloxacin in the treatment of purulent sinusitis-a multicentric study in
      Indian patients.
AB  - Sparfloxacin, a new quinolone antibacterial was used to treat one hundred and
      thirty two patients with acute purulent sinusitis, at a dosage of 400 mg on the
      first day followed by 200 mg once daily for a further four days. A clinically
      successful outcome (defined as disappearance of nasal discharge, fever, pain,
      tenderness over the sinuses and headache) was recorded in 122 ( 95.3%) patients.
      Sparfloxacin was well tolerated. Fourteen adverse experiences were reported in 7
      patients ( 5.3%); they were mainly gastrointestinal and mild. No phototoxic or
      cardiological adverse events occurred. An unusual feature was that Staphylococcus
      aureus and Pseudomonas spp. were the most common bacterial species isolated from
      middle meatal was of patients in this study.

PMID- 23119497
TI  - Medical education: Nasal endoscope and you.
AB  - Although much has been written about the surgical technique of functional
      endoscopic sinus surgery, for sinusitis and nasal polyposes, the other uses of
      the nasal endoscope has not been mentioned, Seven hundred and twenty five
      patients have undergone endoscopic nasal office evaluations and subsequent
      functional endoscopic sinus surgery for various indications in our unit from
      December 1990 to September 1994. Though most of the surgeries were for nasal
      polyposes and sinusitis, we have used the scope for various other indications.

PMID- 23119498
TI  - Use of drill in rhinoplasty (a case report).
AB  - Here we present a case of open rhinoplasty where electric drill was used
      satisfactorily and successfully to correct the deformity of bony dorsum. This
      device has a great potential in rhinoplasty.

PMID- 23119499
TI  - Developmental aspects of the deviated nose -a verwoerd study-.
AB  - In childhood functional, infectious, aesthetic and social problems can result
      from a deviated septum and nose, further research on the anatomic development,
      the mechanism of growth, and the process of wound healing is needed to develop
      surgical techniques that not only correct the present problem but also ensure the
      further normal growth of the septum and nose.

PMID- 23119500
TI  - Reader's forum - 16.

PMID- 23119501
TI  - Journal scan.

PMID- 23119502
TI  - Toynbee joseph.

PMID- 23119503
TI  - Dr. Paras nath sinha (15.1.1904 - 11.11.1980).

PMID- 23119504
TI  - Letters to the editor.

PMID- 23119505
TI  - Course news.

PMID- 23119506
TI  - Workshop news.

PMID- 23119507
TI  - Hearing impairment and deafness-magnitude of problem and strategy for prevention.

PMID- 23119508
TI  - Medical civilization.

PMID- 23119509
TI  - Myringoplasty with temporalis fascia : Analysis of 200 cases.
AB  - Two hundred cases of chronic suppurative otitis media with dry ear were taken up
      for myringoplasty operation by underlay technique through transcanal route.
      Autologous temporalis fascia was used as the graft material in all cases. Surgery
      was done during the period from April 1987 to November 1992. The patients were
      reviewed 5 years after the surgery [1997] and analysed.

PMID- 23119510
TI  - Eustachian tube function test: a new dimension in the management of CSOM.
AB  - Poor eustachian tube function is a major cause of both failure of tympanoplasty
      as well as the persistence of otorrhoea in chronic suppurative otiis media. In
      this study, Eustachian tube function tests were carried out on 631 ears of CSOM
      using an impedance audiometer and the results were analysed. The study showed
      that impaired tubal function is not only the major cause of persistent/recurrent
      otorrhoea in CSOM but is also an important contributory factor for failure of
      tympanoplasty: The results of tympanoplasty were found to be significantly poor
      when carried out in ears having poor tubal function as compared to ears with
      normal tubal function.

PMID- 23119511
TI  - Prevalence of occupational noise induced hearing loss amongst traffic police
      personnel.
AB  - Traffic branch personnel of Pune traffic police were screened for presence of
      noise induced hearing loss. A very significant number (81.2%) showed
      sensorineural hearing loss. The various factors responsible for noise induced
      hearing loss are discussed.

PMID- 23119512
TI  - Rote of adaptation exercises in clinical practice.
AB  - Adaptation, habitution and compensation are the mechanisms involved in
      rehabilitation of vertigo patients. In Vestibular Rehabilitation Therapy (VRT),
      patients are advised to perform a series of maneuvers involving head, eye and
      body movements which stimulate the in-built adaptive mechanisms. Cawthorne and
      Cooksey were the first to describe adaptation exercises, which are further
      modified. Norre has designed VRT test battery of specific exercises. Drug
      treatment used along with VRT should not interfere with the compensation
      mechanism. Anti-vertigo drug Betahistine has been shown to hasten the
      compensation and hence is suitable for use with VRT.

PMID- 23119513
TI  - Transdermal electrical stimulation in sensorineural tinnitus.
AB  - In 73 patients composing 84 ears, with persistent decompensated tinnitus and
      sensorineural deafness, tinnitus suppression was attempted with low frequency,
      low ampere transdermal electrical stimulation (TDES). The causes of tinnitus were
      presbyacusis, unknown aetiology, Noise exposure, otosclerosis, ototoxic drugs,
      Endolymphatic hydrops, labyrinthitis and post head injury. Reduction of tinnitus
      was achieved in 38 of 84 ears. Results were achieved in patients with the
      following order. 1) Unknown aetiology 53.3% 2) Ototoxic drugs 50% 3) Presbyacusis
      45% 4) Labyrinthitis 40% 5) Post head injury, Endolymphatic hydrops &
      otosclerosis 33.3% each. The lasting effect of the tinnitus suppression varied
      from few hours to few weeks. Effective reduction could be re-achieved by re
      stimulation.

PMID- 23119514
TI  - Audiovestibular changes in diabetes mellitus.
AB  - Audiovestibular functions in 50 cases of diabetes mellitus have been evaluated to
      find out the type of hearing loss. Diabetes mellitus causes a significant
      bilateral symmetrical hearing loss at higher frequencies and with the progress of
      disease and added complications the hearing further deteriorates. On control of
      diabetes hearing changes are found to be irreversible. However vestibular
      functions remain uninvolved in cases of diabetes mellitus. A direct correlation
      was found between hearing loss and increasing blood sugar level.

PMID- 23119515
TI  - Haemangioma of the tympanic membrane and external auditory canal.
AB  - An unusual case of haemangioma of external auditory canal in a 16 yrs. old male
      is documented for its rarity.

PMID- 23119516
TI  - Bell's Palsy - herpes simplex virus type-1 a possible causative agent.
AB  - The role of Herpes Simplex Virus Type 1 (HSV-I) in Bell's Palsy was evaluated
      according to clinical symptomatology and serologic findings in a series of 41
      patients seen over two years period. Four fold rise in antibody titre between the
      acute and convalescent sera suggesting a primary infection by HSV-1 was seen in
      21.9% cases, while arise in titre or a constantly high titre suggesting a
      reactivation or recurrent infection by HSV-I was obtained in 29.2% cases. In
      48.9% cases there was a negative antibody titre. No seasonal clustering was
      observed. There was no relation between the recovery of facial nerve function
      with the antibody titre. Key words: Bell's palsy. Herpes simplex virus.

PMID- 23119517
TI  - Eustachian tube functions in atrophic rhinitis-a tympanometeric study.
AB  - The present study was carried out on 60 clinically proved cases of primary
      atrophic rhinitis. Tympanometry was performed to evaluate the Eustachian tube
      functions. It was observed that in majority of cases, atrophic rhinitis does not
      effect the Eustachian tube functions. Only a small number of cases revealed
      hypofunctioning of Eustachian tube.

PMID- 23119518
TI  - Mastoid pneumatization and otosderosis-is there a correlation.
AB  - The environment versus the genetic influence on the size of the mastoid
      pneumatization has been debated for years. A concrete evidence of the influence
      of environmental factors (e.g. inflammation) or heredity on pneumatization is
      still lacking. In this study the extent to mastoid peumatization in thirty
      otosclerotic ears was compared with control ears. The size of mastoid
      pneumatization was measured by the use of Law lateral x-ray projection with the
      help of planimetry. It was found that the average pneumatized area in
      otosclerotic ears was 14.73+ -3.55 cm2 compared to 10.60+3.62 cm2 in control ears
      which was statistically significant. In addition the mean area of mastoid air
      system was found to be more in the operated ears compared to the contralateral
      ears, the difference being statistically significant. However there was no
      correlation of mastoid pneumatization with degree and duration of hearing loss
      and type of otosclerotic focus. Our findings therefore show a link between
      otosclerosis and highly pneumatized mastoids thus indicating a likelihood of
      heredity playing a role in determining final type ot pneumatization.

PMID- 23119519
TI  - Pathological lesions of the external ear : A study of 500 cases.
AB  - A study of pathological lesions of the external ear was carried out during the
      period of two years. All 500 cases were grouped in four categories, Congenital,
      Injury, Infection and Cyst and Tumors. Distribution of lesions in age groups and
      both sexes was studied. Cases were examined to know the etiology, bacteriology
      and clinical presentation of the lesion. The results of the treatvent were
      evaluated.

PMID- 23119520
TI  - Post stapedotomy hyperacousis - a mechanical explanation.
AB  - A mechanical explanation for the hyperacousis that sometimes occurs after
      stapedectomy or stapedotomy is offered.

PMID- 23119521
TI  - The forced response test and myringoplasty results.
AB  - Pre-operative assessment of the Eustachian tube function using a Passive
      Eustachian tube function test 'The Forced response test' and the results of
      tympanoplasty in safe Ch. SOM. Adhesive Otitis Media and Posterosuperior
      inpouching cases have been mentioned in this study.

PMID- 23119522
TI  - Vestibular Schwanomma with normal hearing.
AB  - Schwanomma of the vestibular nerves usually present with sensorineural hearing
      loss of varying degrees. We report here a large (5.5cm x 3.5cm) vestibular
      schwanomma with normal hearing. Other unusual features of this case were the
      young age (20 yrs) of the patient and absence of any otological symptoms.

PMID- 23119523
TI  - Variable presentations in meniere's syndrome.

PMID- 23119524
TI  - Ent trivia.

PMID- 23119525
TI  - Words of wisdom.

PMID- 23119526
TI  - Preventive otorhinolaryngology.
AB  - Curative medicine and curative surgery are no doubt of interest to every body.
      However, a host of diseases in the area of ear, nose & throat are curable, on the
      other hand, a number of them are only controllable, not curable. Several amongst
      them are preventable as such or their complications and sequelae can be prevented
      or minimised. It is high time that more awareness is created towards better
      understanding of the preventive aspect of Otorhinolaryngology practice. The time
      & energy spent on managing complications & sequelae can be easily saved and
      easily utilized in a better way in improving expertise to cure the diseases
      through more research & interaction.

PMID- 23119527
TI  - Computers in otorhinolaryngology; new horizons.
AB  - There has been an explosion in the computers and information technology in the
      past couple of years. Otorhinolaryngology has also seen a number of new
      applications of computers. This article aims to familiarize the reader with
      different uses of computers as applied to the field of Otorhinolaryngology. It
      deals with the role in medical literature search, patient and doctor education,
      medical record keeping telemedicine, internet and E-mail, creating virtual
      environments and its role in FESS. skull base tumours and plastic surgery.

PMID- 23119528
TI  - ENT on the internet.
AB  - Information technology has revolutionized the interactions between professionals
      at all levels. E-mails, information exchange, advertisement and even
      entertainment are all available at click of a mouse from the comfort of one's
      home at any time of the clay or night. It is easy to use, can reach a global
      audience and is a cost-effective method of communication.

PMID- 23119529
TI  - Infrared tympanic thermometry.

PMID- 23119530
TI  - Ceftibuten in ent infections.

PMID- 23119532
TI  - Laser assisted otoendoscopy.

PMID- 23119531
TI  - Budesonide in rhinological practice.

PMID- 23119533
TI  - Letters to the editor.

PMID- 23119534
TI  - Looking for paediatric ENT care.

PMID- 23119535
TI  - Evolution of paediatric otorhinolaryngology.

PMID- 23119536
TI  - Deafness in paediatric age group.
AB  - Incidence and predominant causes of deafness in 20 neonates, 100 infants and 1340
      school going population in the northern region of the Indian subcontinent, was
      investigated by the E. N. T. Department, of Dayanand Medical college and
      Hospital, Ludhiana, Punjab.The recorded incidence of deafness in school going
      children was 12.16% comprising conductive loss (98%) and S. N. loss 2%. Out of
      many cases more notable were chronic rhinitis, tonsillitis, adenoiditis etc.

PMID- 23119537
TI  - A study of the incidence and causation of deafness among the children in the
      tribal population of Manipur and its prevention.
AB  - In a clinico-audiological study of 6,674 children in 24 tribal villages in the
      hills of Manipur in a total population of 18,565, the incidence of deafness is
      found to be 6.62% The incidence of the conductive deafness is 98.64% and that of
      the sensori-neural is 1.35%. Episodes of cold attacks and running nose are found
      to be precursurs of the prevalent conductive deafness. Preventive measures are
      worked out.

PMID- 23119538
TI  - Outcome analysis of functional endoscopie sinonasal surgery for paediatric
      rhinosinusitis using the Lund-Mackay-Kennedy scoring system.
AB  - There are very few indications for surgical management of chronic rhinosinusitis
      in children. This has been partly due to the fact that the definition of what
      qualifies as racalcitrant sinusitis in children is still obscure. There is also
      significant evidence in literature that surgery, especially radical surgery, on
      the nose and sinuses in children would result in some interference with the
      growth of the facio-maxillary skeleton. The advent of Functional Endoscopie sino
      nasal Surgery ( F. E. S. S. ) in recent years has changed the philosophy of
      surgery for paediatric rhinosinusitis and has proven to be an effective choice of
      management in difficult cases. We persent here our experience and preliminary
      results with the use of FESS in nine children with sinonasal disorders including
      cystic fibrosis. The usefulness of the recently described Lund- mackay and
      Kennedy Scoring System for chronic rhinosinusitis in terms of symptom score,
      radiological score, endoscopie score and surgical score has been demonstrated.

PMID- 23119539
TI  - Paediatric facial paralysis. Current opinion in evaluation and management.
AB  - Facial palsy in the paediatric age group is less common than in adults, but poses
      its own problems because clinical diagnosis and investigations are more difficul.
      i' perform. In recent years, electroneuronography (EnoG) has proved to be useful
      for prognosis, and in many endemic areas, neuroborreliosis (Lyme'sDisease) has
      proved to be the commonest cause of this condition in children. Fortunately the
      prognosis in children appears to be better than in adults.

PMID- 23119540
TI  - Functional endoscopie sinus surgery in children.
AB  - Functional Endoscopie Sinus Surgery Which has been introduced in Europe by
      Messerklinger and Stammberger and later on in United States by Kennedy, has now
      become a standard modality of treatment for sinus diseases in our country.
      However, most of the work reported from our country pertain to adult population.
      In this paper, we present our experience in 30 children who underwent Functional
      Endoscopie Sinus Surgery over the past four years. The age of the patients varied
      from 7-14 years. All the patients tolerated the procedure well and there was no
      major complication. Follow-up period varied from 9-39 months with a mean follow
      up of 18.3 months. Out of 30 patients, 27 patients were available for long term
      assessment of results. 18 patients (66.67%) reported complete improvement of
      symptoms, while 6 patients (22.22%) had partial improvement. 3 patients (11.11%)
      showed no improvement. The results of this small series reveal that Functional
      Endoscopie Sinus Suregery has a definite role in the treatment of sinus disease
      in children.

PMID- 23119541
TI  - Acute respiratory tract obstruction in children.
AB  - 35 cases of acute respiratory tract obstruction in paediatric age group who
      needed surgical intervention in the form of bronchoscopy, tracheostomy or both
      are reviewed here. All these patients were seen and managed at National Iranian
      Oil company Hospital Ummeidiya Khouzestan Iran, from April 1985 to April 1988.
      The results obtained with a review of use of instruments is described. Most of
      the patients presented with foreign body inhalations, some due to allergic oedema
      and one case had laryngeal cyst causing respiratory tract obstruction.

PMID- 23119542
TI  - Current practice of paediatric chochlear implantation in nottingham.
AB  - The number of integrated paediatric cochlear implantation programme are very few
      in the world. In U.K. this pioneering integrated paediatric chochlear
      implantation programme has been started in the year 1989 under the supervision of
      group of dedicated paediatric personnel comprising of ENT surgeons, neuro
      radiologist, audiologist, speech therapist, orthophonists, teachers of the deaf
      and others associated with the deaf children. Only the surgical procedure of
      cochlear implantation is not the answer of a profound sensorineural deaf child
      who can not be helped by conventional hearing aids. Proper selection of the
      cases, pre-operative counselling, pre-operative audiological and non-audiological
      investigations are of immense value. Similarly the programme following surgery as
      a team approach is equally important for proper rehabilitation of profound
      sensorineural deaf child who can not be helped by conventional hearing aids.

PMID- 23119543
TI  - Embryonal rhabdomyosarcoma with intracranial extension.
AB  - A case of embryonal rhabdomyosarcoma of the middle ear presenting with facial
      paralysis and a polypoidal aural mass who subsequently had convulsions due to
      intracranial extension is presented for its rarity.

PMID- 23119544
TI  - A.B.R. in Nager type acrofacial dysostosis syndrome.
AB  - The acrofacial dysostosis of nager is a very rare hereditary syndrome in which
      findings of mandibulofacial dysostosis are associated with defects of the limbs.
      The developmental defects of the mesoderm if accompany the neurectodermal
      malformations, result in mental retardation and sensorineural hearing impairment.
      The conductive type of hearing loss is mostly encountered in Nager's syndrome but
      here we present a case with sensorineural involvement, along with its analysis of
      auditory brainstem evoked response audiometry (ABR).

PMID- 23119545
TI  - Allergie affections of the larynx in children-a clinico pathological study.
AB  - Laryngeal manifestation of allergy though less common than, Rhinosinusitis,
      tubotympanitis and bronchopulmanary allergy but it is not that uncommon which is
      usually misdiagnosed and mistreated in children. Hence the importance of larynx
      as the allergic shock organ in children with spasmodic croup and laryngotracheo
      bronchits. In the present study in children bellow five years, presenting with
      stridor and/or hoarsness were evaluated regarding the history of allergy, direct
      laryngoscopic finding, mesurement of serum 1 g E. Presence of eosinophilia and
      histopathological examination of laryngeal biopsy. Out of the 80 cases studied 9
      cases (11.2%) presented with associated allergic manifestation, 8 cases (10%)
      having family history of allergy, 4 cases (5%) having raised serum 1 g E, 12
      cases (15%) with eosinophilia 3 cases (3.75%) with eosinophilic infiltration on
      histopathological examination of the biopsy material taken during the direct
      laryngoscopy.

PMID- 23119546
TI  - Myxoma of the maxillary sinus.
AB  - A case of Myxoma involving the maxillary sinus in an 11 year old girl is being
      reported for its rare oCcurance in children.

PMID- 23119547
TI  - Congenital nasal teratoma.

PMID- 23119548
TI  - Oral submucous fibrosis in paediatric age group.
AB  - Oral submucous fibrosis is common in the Indian subcontinent, but only a few
      cases have been reported in the paediatric age group. An interesting case of
      submucous fibrosis in a child aged 8 years is reported . A brief review of
      literature and management of the patient are discussed.

PMID- 23119549
TI  - Nasal glioma and ala defects.
AB  - Congenital nasal mid-line masses are rare, and nasal gliomas account for
      approximately 5% of all of them. They are benign lesion containing "ectopic brain
      tissue" Encephaloceles and gliomas are thought to have a close embryological
      origin and faulty closure of the anterior nasopore is suggested as a possible
      explanation. We present the case of an eight month old male who presented to us
      at Great Ormond Street Hospital for Sick Children, London. He had a left sided
      nasal glioma and also an ipsilateral ala notch. Only two other reference were
      found commenting on this unusual link between nasal glioma's and ipsilateral ala
      defects. This association perhaps suggests an alternative more complex
      embryological origin to the nasal glioma.

PMID- 23119550
TI  - Giant dentigerous cyst.
AB  - Dentigerous cyst - a cyst of dental origin, though common in lower jaw is
      relatively uncommon in upper jaw. Here a 14 years, F, presented with huge
      swelling of unilateral maxilla and clinicoradiologically diagnosed as dentigerous
      cyst is being reported along with brief review of literature.

PMID- 23119551
TI  - Melanotic neuroectodermal tumour of maxilla in infancy.
AB  - Melanotic neruoectodermal tumour of infancy is an uncommon pigmented neural crest
      derivative. It is usually found affecting children aged one year or less. We
      present a case report of a four month old male infant with this tumour arising
      from the right maxilla showing extensive involovement of the surrounding bony and
      soft tissue structures.

PMID- 23119552
TI  - Fibroma of tonsil.
AB  - Benign neoplasms of the tonsillar region are rare and these include haemangiomas,
      fibromas, lipomas and schwannomas (Friedmann I, 1986). True fibromas of oral
      cavity and oropharynxes are very rare (Waal I. V., Snow, G. B. 1993). Fibromas
      have been recorded in nasal cavity, pharynx and larynx (Fu Y. S., Perzin K. H.
      1976), We report a case of fibroma of tonsil for its rarity.

PMID- 23119553
TI  - Staples as foreign-body oesophagus.
AB  - (A. bunch of staples is being reported as oesophageal foreign body in a five and
      half month old infant. Radiologically these staples appeared as single compact
      bunch, however, (during oesophagoscopy these were removed in two and threes.

PMID- 23119554
TI  - Waardenburg's syndrome a rare entity.

PMID- 23119555
TI  - Psychology of tinnitus in children.
AB  - Parents usually give the history of symptoms to us whenever a child is brought to
      us. Child is neither asked about his symptom nor his feelings related to the
      problem by most of jus. This paradox often results into resentment by the child
      biaking our examination more difficult. History given by a child often differs
      from that given by his parents. More than treating the Paediatric patients by
      medicines and surgery by special approach, technique or equipments, it is the
      understanding the Psychology of the children complaining of symptoms or suffering
      from a disease makes an ENT specialist a Paediatric ENT specialist. Child
      Psychology for paediatric ENT disorders are neither found in any book. One learns
      by keeping the eyes and ears open, by constant observation and analysis and from
      the experience of seniors.

PMID- 23119556
TI  - Adenomatoid odontogenic tumour of the maxillary sinus.
AB  - A typical adenomatoid odontogenic tumour removed from the left maxillary sinus of
      a fifteen years old male is reported.

PMID- 23119557
TI  - A time frame of critical/sensitive periods of language development.
AB  - By a focus on three essential elements of language, phonology, semantics, and
      syntax, a time frame for critical/sensitive periods of language development is
      presented as a model of central auditory nervous system flexibility. Several
      studies support the hypothesis that the critical/sensitive period of phonology is
      from the sixth month of fetal life through the 12th month of infancy. Data
      indicates that the critical/sensitive periods for syntax runs through the fourth
      year of life, and for semantics through the 15th or 16th year of life. The data
      indicate that there is a time dependent series of functions in sequence that is
      based on responsive adaptations made by the CNS to psychophysical and
      electrophysiological stimuli.

PMID- 23119558
TI  - Rhabdomyosarcoma of nasopharynx.
AB  - Rhabdomyosarcoma is a highly invasive malignant tumour arising from the
      mesenchymal tissue. Here, we reported a rare case of embryonal rhadomyosarcoma of
      nasopharynx with extension to different spaces of base of skull and orbit. Rarity
      of the case difficulty in diagnosis encourages its reporting.

PMID- 23119559
TI  - Cetirizine and astemizole in allergic rhinitis a comparative study.
AB  - The efficacy, safety and side effects of Cetirizine and Astemizole were compared
      with Pheniramine maleate in sixty cases of allergic rhinitis. All medications
      were stopped one week prior to treatment. Cetirizine, Astemizole or Pheniramine
      maleate were given as a single daily dose for 15 days. On completion of treatment
      results were evaluated subjectively as well as objectively, Cetirizine and
      Astemizole were found to be more effective than Pheniramine maleate. The side
      effects were minimum with Cetirizine.

PMID- 23119560
TI  - A study on Etio-Pathology of proptosis in otorhinolaryngology.
AB  - Twenty cases which presented with proptosis during the period of 1 year at the
      Madras Medical College & Govt. General Hospital, Madras, India were taken up for
      this prospective study. After a detailed ENT and ophthalmological examination,
      exophthalmometric readings were done on all cases. The etiological causes and
      other factors were analysed. Malignancies and benign tumours and tumour like
      lesions were found to be the commonest cause of proptosis. Infections which were
      once responsible for most cases of proptosis formed only a very small proportion.
      A person presenting with protosis as the only sign is most likely to suffer from
      a benign tumour or tumour like lesion while presence of other eye signs should
      raise the possibility of malignancies. The direction of proptosis was found to be
      more useful than exophthalmometric readings in determining the site of lesion.

PMID- 23119561
TI  - Concomitant cisplatin and radiationtherapy in advanced head and neck cancers:.
AB  - Single modality treatment is not suitable to the treatment of Head and Neck
      cancers and surgery is often mutilating. Concomitant chemotherapy and radiation
      produce good local control. In this study cisplating givenconcomitantly with
      radiation is compared with radiation alone in advanced head and neck cancers.

PMID- 23119563
TI  - Carcinoma of the major salivary glands. analysis of the role of radiation
      therapy.
AB  - Forty-six patients of major salivary gland tumors were retrospectively studied.
      There were 40 (87%) parotid and 6 (13%) sub-mandibular tumors. Patients receiving
      adjuvant radiation therapy after a radical surgery fared much better (86%)
      complete response (CR) as compared to those treated for recurrent or inoperable
      disease (50% CR). The 5-year overall and disease free survival rates for the
      entire group is 70% and 34% respectively. These findings and a review of
      literature suggests that adjuvant post operative radition therapy is recommended
      to reduce the risk of post surgical recurrence.

PMID- 23119562
TI  - Recent advances in the molecular biology of head and neck tumours.
AB  - Our knowlcwdge about the genetic basis of head and neck tumours is accumulating
      fast. This article reviews the important advances in this area over the last
      decade and its implications for the future. Newer aspects of gene therapy,
      molecular staging and understanding head and neck carcinogenesis on a molecular
      level are outlined.

PMID- 23119564
TI  - Hemangioendothelioma of orbit.
AB  - Hemangioendothelioma of the orbit is a rare condition which usually occurs in
      young adult with mean age group of 24 years. Very few cases had been reported in
      the literature. We describe here a case of hemangioendothelioma in a female of 30
      years who came with history of pen-etrating foreign body entering into right eye
      and fluctuating painful swelling in the lower lid with decrease in the vision.
      The patient's presentation simulated malignancy of maxillary an-trum, however,
      the diagnosis was confirmed by histopathology.

PMID- 23119565
TI  - Bilateral intra parotid tubercular lymphadenitis.
AB  - Tubercular parotitis is an extremely rare clinical condition which is difficult
      to diagnose. The rarity of this condition can be seen from the evidence of only a
      few reported cases in the litera-ture. Tubercular infection is quiet common in
      this part of the world, but Tubercular Parotitis is still a rarity. A case of
      Bilateral tubercular parotitis diagnosed by FNAC, showing tubercular involvement
      of the intra parotid lymph node is presented due to its rarity.

PMID- 23119566
TI  - Melkersson-rosenthal syndrome.
AB  - Melkersson - Rosenthal syndrome was described by Melkersson and Rosenthal
      separately in the year 1928 and 1931 respectively. It is supposed to be a rare
      syndrome of bilateral alternating recurrent facial paralysis alongwith fissured
      tongue and oedema of the lips, face and eyelids. A case of Melkersson - Rosenthal
      syndrome is reported with all the classic findings which is a rarity. In this
      case there was alternating facial paralysis to begin with followed by bilateral
      paralysis third time, along with oedema of lips and face, fissured tongue, and
      dialation of sig-moid colon with absence of haustrations.

PMID- 23119567
TI  - Headache and the otolaryngologist.

PMID- 23119568
TI  - Synovial sarcoma of the head and neck a report of 3 cases.
AB  - Synovial sarcoma is very rare and highly malignant tumour of the head and neck.
      Only 3 cases of synovial sarcoma have been treated 1980-1997 in Kasturba Medical
      College, Manipal. Treat-ment involved extensive surgical resection of the tumour
      (with neck dissection in two cases); and post- operative radiotherapy and
      chemotherapy in one case. Behaviour of the tumour was followed up till August
      1997. It remains in our experience that synovial sarcoma, though a tumour or poor
      prognosis if treated by adequate tumour resection and adjunctive radiotherapy and
      chemotherapy, has good patient survival.

PMID- 23119569
TI  - Moebius syndrome (moebius sequence).
AB  - Moebius Syndrome is one of the rare disorder amongst the oromandibular limb
      hypogenesis. It is of a unknown atiology with sporadic occurrence in which there
      is congenital bilateral facial palsy,-bilateral involvement of abducent nerve
      along with other cranial nerves like III, V, IX, X, Xllth and the patient having
      masklike expressionless face. We are reporting a case of Moebius Sequence who
      presented to us in the department of ENT and Head and Neck Surgery, Baroda.

PMID- 23119570
TI  - Surgical management of cervical tracheal stenosis.
AB  - Postintubation cervical tracheal stenosis managed by tracheal resection with
      supralaryngeal release and end to end anostomosis, without postoperative stent or
      endotracheal tube. Cervical tracheal stenosis of <3 cm in length can be managed
      by E.N.T. surgeon alone.

PMID- 23119571
TI  - Osteomyelitis of the skull base due to mucormycosis.

PMID- 23119572
TI  - Cysticercosis of submandibular duct.
AB  - Cysticercosis is a common platyhelminthes intestinal infection but its
      presentation in subman-dibular duct is unknown. We report one such case.

PMID- 23119573
TI  - Temporosphenoid giant cell tumour.
AB  - Only a few cases of Giant Cell tumours of temporal and sphenoid bones have been
      documented in English literature. Concurrent temporoshenoid location is extremely
      rare for a Giant Cell Tumour. These locally aggressive bonedestructive tumours
      usually have a fairly predictable pat-tern of spread. We present here a case of
      Temporosphenoid Giant Cell Tumour that exhibited an unusual pattern of spread.
      This tumour was removed in a single stage without any untoward sequelae. A brief
      review of literature is included.

PMID- 23119574
TI  - Sturge weber syndrome - A case report.

PMID- 23119575
TI  - True giant cell tumour of maxilla.

PMID- 23119576
TI  - An unusual massive head-neck tumor and its surgical management.
AB  - An unusually massive (15cm x 15cm x 15cm)and heavy tumor, (2.85 kg) one of the
      largest of its kind, was present in a sixty years old male patient who attended
      the E.N.T. out-patient depart-ment. The patient was Australia antigen positive.
      The case presented a surgical challenge be-cause of its large size and skin
      adherence. Complete excision of the tumor and closure of the resultant facial
      defect, (5cm. x 5cm) with split-thickness skin graft was the treatment modality
      followed. There is no recurrence, and the prognosis appears to be good.

PMID- 23119577
TI  - Diagnostic role of ultrasonography in neck swellings.
AB  - Diagnostic Role of Ultrasonography in Neck Swellings The study of
      ultrasonographic features of various neck swellings in fifty patients was done.
      There were 22 thyroid and thyroid related swelling, 8 salivary gland lesions, 9
      lymph nodes and 14 swellings of miscellaneous origin. Various ultrasonographic
      features like echogenicity, echotextures were noted. There were no specific
      echogenicity in benign and malignant thyroid neoplasms. Various ultrasonographic
      features of benign and malignant salivary neoplasms and lymph nodes are
      described. Specific sonographic features of various miscellaneous neck swellings
      are also described.

PMID- 23119578
TI  - Carotid artery resection and vein grafting for malignancy.
AB  - Neck recurrence following multi-modality therapy generally indicates a poor
      prognosis. Many of these recurrences are considered inoperable due to invasion of
      the Internal Carotid artery. Resec-tion of the carotid artery in these
      circumstances is associated with a high risk of neurological morbidity. However,
      in certain selected patients, resection of the carotid artery and replacement
      with a sephenous vein graft has been shown to be both safe and to provide a
      reasonable chance of disease control.This paper presents a case report of a 50
      years old male with carcinoma of the larynx, who following radiotherapy and
      salage laryngectomy, developed a neck recurrence invading the carotid artery. A
      neck dissection along with carotid artery resection and vascular continuity using
      a saphenous vein graft was performed successfully. The surgical technique is
      presented alone with the review of relevant literature.

PMID- 23119579
TI  - Hamartoma of the head and neck.
AB  - Hamartoma is a relatively uncommon lesion in head and neck region. Although
      hamartoma is not a true neoplasm, but it behaves in tumour like manner in many
      ways. In this paper five cases of hamartoma of head and neck region, one case
      each from soft tissue cheek, soft tissue neck, maxilla, gum margin and tongue are
      reported and pertinent literature is reviewed.

PMID- 23119580
TI  - Recurrent ameloblastoma of the mandible.
AB  - Ameloblastoma is an agressive locally recurring neoplasm of odentogenic
      epithelium. Here we describe a case of mandibular ameloblastoma with 12 yrs.
      history of local recurrences followed with history of excision twice (10 yrs. and
      7 years back).

PMID- 23119581
TI  - "Juvenile alveolar rhabdomyosarcoma of mandible".
AB  - Rhabdomyomatous tumours are the malignant neoplasms of complex composition and
      deriva-tion. Three varities of Rhabdomyosarcoma are described. These are -1.
      Pleomorphic 2. Embryonal 3. AlveolarJuvenile Alveolar Rhabdomyosarcoma usually
      affects extremities and less commonly trunk, or-bit, soft tissues of the face
      (Cheek), Neck and oral cavity including the tongue and palate. A case of Juvenile
      Alveolar Rhabdomyosarcoma of Mandible is being reported. Relevant literature is
      reviewed.

PMID- 23119582
TI  - Papillary carcinoma in a thyroglossal cyst: report of a case and review of
      literature.
AB  - A 29-years old male presenting with a midline neck swelling four centimetres in
      diameter of one years duration was diagnosed to have a thyroglossal cyst. He
      underwent a Sistrunk's operation. Histological examination of the specimen
      revealed a papillary thyroid carcinoma limited to the cyst wall. The thyroid scan
      was normal indicating no further need for surgery. The patient has been on
      suppressive therapy with thyroxin for one year and is currently disease-free. A
      review of literature is also presented.

PMID- 23119583
TI  - Role of temporalis musculofascial transposition for obliteration of the
      exenterated orbit.
AB  - An exenterated orbit left as such tends to encrust, become odorous and remains a
      potential source of infection besides looking unsightly. To overcome these
      problems we transposed the temporalis musculofascial complex through a lateral
      orbitotomy for primary and secondary oblit-eration of the orbit in two cases
      each. In each patient the orbit was exenterated to ablate a neoplasm. In all
      cases the procedure yielded a problem-free orbit with good cosmesis. The
      temporalis musculofascial transposition complex is a simple means of obliterating
      the orbit particularly in the Indian context wherein prosthetic orbital devices
      are often unavailable.

PMID- 23119584
TI  - Widening the horizons of otolaryngologist an interdisciplinary approach for
      surgical problems of cervical spine.
AB  - Till recent past the realm of ENT surgeons was limited to tonsils and mastoids.
      But with the passage of time and strides made by the Biomedical Engineering, the
      horizon has widened and the Otolaryngology has kept pace with other medical
      specialities. Lesions of Clivus, cervicomedullary junction and cervical vertebra
      often present difficulty to the Neuro Surgeon and Orthopaedic Surgeon. The role
      of ENT surgeon in these cases of cervical spine surgery can be significant. A
      successful attempt has been made to approach various levels of cervical spine
      anteriorly either transorally, transpharyngeally or transcervically.Although
      these techniques are well suited to the training and experience of the Head &
      Neck +/- surgeon, it is our perception that the procedure is underused by the
      members of our speciality. Although these approaches are safe and reliable, it is
      not part of the Otolaryngologist's usual surgical armamentarium.In the present
      study a series of thirteen patients presented between February '91 and July '94,
      with various pathologies of Cervical Spine with or without neurological deficits
      is reviewed. The surgical technique is discussed and methods to prevent potential
      complications and adverse sequelae are also addressed.

PMID- 23119585
TI  - Foreign bodies in ear, nose and throat (Predictions and management).
AB  - Management of a patient with foreign body (FB) in the ENT areas is an art. FB in
      the respiratory tract is fraught with respiratory obstruction and even death,
      rarely though, especially in infants and children, if not intervened in time.
      Fair prediction can be made as to the site and side of lodgment of FB in lower
      respiratory tract depending on the age of the patient so that timely intervention
      on the involved side can be made without undertaking haphazard scopy.

PMID- 23119586
TI  - A case of foreign body in the subglottic region.
AB  - An impacted foreign body in the subglottis is a rare cause of upper airway
      obstruction in children. More often than not the diagnosis is delayed; especially
      where proper history is not forthcoming. This peculiar condition can masquade as
      laryngotracheobronchitis or a croup. Though it is rare, a foreign body in the
      subglottis should be kept in mind in the investigation of a child with stridor.

PMID- 23119587
TI  - Unusual cases of foreign bodies in air passage in children.
AB  - Tracheobronchial foreign bodies when not treated promptly continue to be a source
      of morbidity and mortality specially in the paediatric population. Chevaliar
      Jackson, through meticulous analysis of mechanical problems related to foreign
      bodies in the air and food passages and their solution, created a science of
      rehearsed and tested instrumental techniques for their extraction (Jackson and
      Jackson, 1936). They developed instruments to achieve remarkable results with an
      almost unbelievably low morbidity and mortality.Aspiration of foreign bodies is
      seen more commonly in the paediatric age group and nearly 94% of them occur in
      infants and children (Holinger and Holinger, 1978). According to Jackson, nearly
      90% of these foreign body accidents are due to carelessness, and are therefore
      avoidable. We present two unusual cases of inorganic foreign bodies in the air
      passages in children with special reference to the problems encountered in their
      diagnosis and management.

PMID- 23119588
TI  - Retained oesophageal foreign bodies - report of three cases.
AB  - Incarceration of foreign bodies in the oesophagus is a welknown clinical problem.
      Either children in the first decade of life or adults between 50 and 60 years of
      age are the commoner victims. Types of oesophageal foreign bodies differ
      according to age, being toys and coins in the childhood and dental prosthesis,
      fish bones or bone splinters in adulthood. Severe oesophageal injury due to
      incarceration of foreign bodies is exceptional in children but rule in adults.
      Foreign bodies can be retrieved from the oesophagus successfully in 99% cases
      with a mortality of less than 0.2%. Three cases have been discussed here, all
      having retained foreign bodies in their oesophagus for varying length of time
      with unique problems. Different management strategies were planned and
      successfully applied in these cases. All of them survived and doing well after
      reasonable period of follow up.

PMID- 23119589
TI  - Foreign bodies in the larynx.
AB  - Inhalation of foreign body is a serious event. A very small proportion of foreign
      bodies get impacted in the larnyx. Any [foreign body in the larynx presents
      usually as a respiratory (emergency, when urgent recognition is required to
      prevent disaster. Two cases of fish bone impacted in the larynx, one in
      anteroposterior and another in coronal disposition are presented here along with
      a brief review of literature.

PMID- 23119590
TI  - Concept of foreign body-its past and present.
AB  - Believe it or not, once upon a time, to remove a foreign body from the ear canal,
      the clinicians used to introduce the severed head of a living lizard which was
      still then gasping for breath. It was hoped that, the opening and closing jaw
      movements of the gasping lizard would at one time grasp the Foreign Body.
      Afterwards the removal of the lizard's head would also lead to the removal of the
      Foreign Body.Today the safe and simple removal is not considered as the ultimate
      treatment of Foreign body. Amongst the victims of self introduced Foreign bodies,
      are mostly children. Specially those who do it repeatedly and on others, are
      thought to be mentally retarded or frustrated. Such children should be subjected
      to Psychoanalysis and if the said study confirms one to be so, he should be given
      appropriate treatment. This will help him to grow normally by alleviating his
      various other behavioural disorders. In addition, it will stop his tendeny to do
      it again and save him suffering from problems of other mental disorders which can
      crop up in his future life if left untreated.

PMID- 23119591
TI  - A rare long standing foreign body in the larynx.
AB  - An accidentally inhaled foreign body (A metallic toe ring) inside the larynx of a
      2 1/2 year old child has been studied. It remained in the larynx for 8 months
      before detection and removal.

PMID- 23119592
TI  - Whistle (EB.) in tracheobronchial tree (in paediatric age group) - 4 years study.
AB  - Segmented whistles found in compressible toys often get lodged in the
      tracheobronchial tree of infants and children and may remain asymptomatic as
      patients keep on breathing normally through the lumen of the whistle without much
      difficulty. Here 10 such cases are reported. The problems encountered in their
      management are also discussed.

PMID- 23119593
TI  - Play safe with safety pins.
AB  - Three cases of Safety pins in the aerodigestive tract have been presented here
      with a brief review of litereture.

PMID- 23119594
TI  - Migrating foreign body in bronchus.
AB  - Bronchial foreign bodies are often clinically encountered especially in small
      children. We report a case of an unusual foreign body in an adult bronchus
      showing migratory movements.

PMID- 23119595
TI  - An arrow in the nasal cavity, ethmoid and nasopharynx.
AB  - A penetrating foreign body (Metallic arrow) involving the ethmoidal air cells
      nose and nasopharynx is being reported.

PMID- 23119596
TI  - A case report of an unusual foreign body in oropharynx.
AB  - A rare case of an unusual foreign body (Torch) in oropharynx in 25 years young
      boy is reported here alongwith management and discussion.

PMID- 23119597
TI  - Multiple foreign bodies in the tracheobronchial tree.
AB  - Inhaled foreign bodies in respiratory tract are usually single. Multiple foreign
      bodies in the tracheobronchial tree are extremly rare. A nine-month-old infant
      with four pieces of belelnut in right bronchus is reported and its management is
      discussed.

PMID- 23119598
TI  - Unusual foreign bodies in ear, nose and throat practice.
AB  - Ear, Nose and Throat practice presents the surgeons with an amazing variety of
      foreign bodies to deal with, some of them truly unusual. Presented here are two
      cases with foreign bodies unusual in nature, extracted by improvisation.

PMID- 23119599
TI  - Unusual course of airway foreign body.

PMID- 23119600
TI  - An unusual foreign body in oesophagus.
AB  - Foreign body in the esophagus is not an unusual finding. Coin in children and
      bone fragments in adults are commonly observed foreign bodies. Usually foreign
      bodies are removed within few hours to few days. Forgotten or unattended foreign
      bodies are seen in either mentally retarded patients or in children. We are
      reporting here a case, having unusual foreign body in oesophagus, i.e. a thorn of
      babul tree since one month, presented as perioeso-phagitis with dysphagea in a
      mentally retarded child of 12 years.

PMID- 23119601
TI  - Unusual foreign body in the neck.
AB  - An unusual FB. (broken end of a metallic knief) in the neck is reported. The case
      is cousidered as unusual because no history of FB entering into the neck during
      the injury was available and the wound over the FB was healed. In addition,
      patient was otherwise Asmyptomatic, the reason why the diagnosis was delayed.

PMID- 23119602
TI  - Unusual impacted flying foreign body in thyroid lobe.
AB  - A case of impacted flying foreign body (metallic splinter) in the thyroid lobe
      reported for its rarity.

PMID- 23119603
TI  - Unusual foreign body in the nasopharynx and ethmoidal sinus.
AB  - Foreign bodies in the upper aero-digestive tract are a common presentation in the
      E.N.T. Department of any hospital. Their management calls for the skills of an
      E.N.T. Surgeon to be put to test. Though usually non problematic, one can
      encounter serious difficulties in the removal of such F.B.

PMID- 23119604
TI  - An unusual foreign body producing acute laryngeal obstruction.
AB  - This paper present an unusual case of acute upper respiratory obstruction due to
      an inhaled grape necessitating acute surgical measures. Study of the literature
      proves laryngeal foreign bodies to be a rare occurrence but infinitely more
      dramatic and life-threatening than either oesophageal or bronchial foreign
      bodies. Successful management entails prompt surgical intervention coupled with
      at times, surgical ingenuity.

PMID- 23119605
TI  - An unusual impacted foreign body oesophagus in an infant.
AB  - Although foreign bodies in aerodigestive tract are quite common in children, but
      presence of an impacted, sharp foreign body which needed removal by trans
      cervical oesophagotomy is quite rare and is thus being reported.

PMID- 23119606
TI  - Paediatric nasopharyngeal foreign bodies.
AB  - Two unusual cases of foreign bodies, a metallic whistle and a wooden gutty with a
      threaded screw, lodged in the nasopharyngeal region are reported. The rare
      feature of absence pf symptoms inspite of impaction for long duration in the
      paediatric age group is recorded.

PMID- 23119608
TI  - Into the new millennium with a new perspective.

PMID- 23119607
TI  - A neglected foreign body in the oesophagus.
AB  - Foreign body ingestion is a clinical emergency requiring prompt action to ensure
      speedy recovery and minimise the complications. We report here a case of a
      neglected foreign body which remained within the oesophagus of a child for 6
      years before the diagnosis was made and appropriate treatment given.

PMID- 23119609
TI  - Writing a scientific article.

PMID- 23119610
TI  - Functional endoscopic sinus surgery results in 69 patients.
AB  - Sixty nine patients with sinonasal symptoms were subjected to diagnostic
      endoscopy. Functional endoscopic sinus surgery was done subsequently for chronic
      sinusitis in 42 patients, for ethmoidal polypi in 18 patients and for
      antrochoanal polypi in 9 patients. A follow up of 18 to 36 months ( mean 27
      months) reveals a success rate of 84% in the overall study, 81.5% in patients
      with chronic sinusitis alone, 87.5% in ethmoidal polypi and 100% in patients with
      antrochoanal polyps.

PMID- 23119611
TI  - Nasal dermoids - our experience.
AB  - Dermoid Cysts and fistulas of the nose represent an uncommon embryological error.
      The frequency of misdiagnosis and recurrences of this lesion indicates the lack
      of awareness of its occult ramifications which lead to a compromised incomplete
      excision and are classified as "misadventures", We would like to present our
      experience with nasal dermoids - their clinical presentation and management.

PMID- 23119612
TI  - Functional endoscopic sinus surgery- a newer surgical concept in the management
      of chronic sinusitis.
AB  - Two hundred and ten patients suffering from chronic hyperplastic rhinosinusitis
      refractory to medical treatment were subjected to Functional Endoscopic Sinus
      Surgery using the classical Messerklinger technique ( MT FESS). Of these, 147
      (70%) had complete relief of symptoms, 39 (18.5%) had partial relief of symptoms
      and 15(7.17%) had no/poor relief of symptoms in the follow-up period varying from
      6-33 months (Mean 18.3 months). Sine (4.2%) patients were lost to follow-up. The
      merits and demerits of Functional Endoscopic Sinus Surgery are discussed.

PMID- 23119613
TI  - Low dose ct in chronic sinusitis.
AB  - Role of low dose CT was assessed in 50 patients of chronic sinusitis. CT easily
      picks up the disease and predisposing anatomic variants, which were observed, in
      78% of cases. The commonest anatomical variants was deviated nasal septum
      (38%),other variants found were concha bullosa in (28%) and Helle cell in 28%
      cases. The commonest disease pattern was osteomeatal unit pattern in 36% case.
      Infundibular pattern was seen in 23%, sphenoethmoidal recess pattern in 12% and
      sino-nasal polypopsis pattern was present in 16% of the cases. Low dose CT is
      preferred as it gives as good results as standard CT There is very little chances
      of irradiation hazard even when it has to be employed repeatedly.

PMID- 23119614
TI  - Endoscopic dacryocystorhinostomy and retrograde nasolacrimal duct dilatation with
      cannulation: our experience.
AB  - Endoscopic endonasal dacryocystorhinostomy [EDCR] is considered to be a superior
      alternative technique to the conventional external dacryocystorhinostomy [DCR],
      both in primary and secondary cases. It is of particular value in children and
      young adults as it avoids an external scar. Sixteen cases of chronic dacryo
      cystitis were treated by the endoscopic technique, including 8 revision cases of
      failed external approach. In all cases except one, a patent nasolacrimal fistula
      was noted, with a success rate of 93.7%. The authors share their experience in
      EDCR and review the relevant literature.

PMID- 23119615
TI  - Transdermal electrical stimulation in sensorineural TINNITUS.
AB  - In 73 patients, comprising of 84 ears, with persistent decompensated tinnitus and
      sensorineu-ral deafness, tinnitus suppression was attempted with low frequency,
      low ampere transdermal electrical stimula-tion (TDES). The causes of tinnitus
      were presbyacusis, unknown aetiology, noise exposure, otosclerosis, ototoxic
      drugs, endolymphatic hydrops, labyrinthitis and post head injury. Reduction of
      tinnitus was achieved in 38 of 84 ears. Results i.e. improvement were achieved in
      patients in the following order. (1). Unknown aetiology 53.3% .(2).Ototoxic drugs
      50%. (3). Presbyacusis 45%. (4). Labyrinthitis 40% (5) Post head injury,
      Endolymphatic hydrops & Otosclerosis 33.3% each. The lasting effect of the
      tinnitus suppression varied from few hours to few weeks. Effective reduction
      could be re-achieved by re-stimulation.

PMID- 23119616
TI  - A general study of carcinoma oesophagus in Assam.
AB  - A general study has been performed in the Gauhati Medical College Hospital(GMCH),
      Gauhati on Carcinoma oesophagus. Altogether 687 cases of carcinoma oesophagus
      cases were admitted in. the CMCH during the years s 1988 to 1992 i.e. 5 years
      period of time and studied. This study recorded incidence, age and sex
      distribution, presenting symptoms, methods of diagnosis, relation to tobacco
      habit and also treatment procedures and prognosis were also recorded along with
      its analysis.

PMID- 23119617
TI  - Leukoplakia: A correlative study of clinical picture and cytohistopathology.
AB  - Leukoplakia means a " White Patch", and is defined as a white patch or plaque on
      the mu-cosa that cannot be rubbed off and is not ascribable to any other
      condition(Fig. 1). Many patients come to the O.P.D. with presentation of white
      patch, ulcer, excessive salivation, trismus, increased sensitivity to chilies and
      burning sensation, dysphagia, otalgia and ultimately growth. Advanced countries
      have attained sophistication in oncopathy (like tumor marker, tumor antibodies).
      But we are still in search of an efficient screening method by which the
      cytologist can point accurately towards the nature of the disease within a few
      hours. That is why a correlative study of clinical picture and
      cytohistopathological findings had been studied in 74 cases in last three years,
      which were clinically diagnosed as leukoplakia in the out patient department of
      ENT in M.L.B. Medical College. Jhansi. In oral malignancy, it is extremely
      desirable that a correct and reliable method is adopted for early diagnosis and
      treatment, which can be instituted at a stage when the chances for cure are
      definitely greater.

PMID- 23119618
TI  - A comparative study of external and endoscopic endonasal dacryocystorhinostomy -
      a preliminary report.
AB  - This prospective study was done ta compare the results of external and endonasal
      dacryocys-torhinostomy (DCR). 6 patients were studied under each group. Success
      rate for external DCR was 93.3% and endonasal was DCR 100%. The technique, merits
      and disadvantages of both the procedures are discussed as well as the advantages
      of endonasal DCR highlighted.

PMID- 23119619
TI  - Concha bullosa: Frequency and appearances on sinonasal CT.
AB  - Aeration of the middle turbinate, termed "Concha bullosa", is one of the most
      common, obstructive, anatomic variants seen in patients with sinusitis. The
      present study was carried out on 150 patients of chronic sinusitis, who underwent
      CT scan paranasal sinuses, coronal section prior to Functional Endoscopic Sinus
      Surgery (FESS). The CT Scans were evaluated to detect the incidence of Concha
      bullosa and its types, the significance of Concha bullosa in genesis of
      osteomeatal complex disease and relation between type of Concha bullosa and
      osteomeatal complex disease. Later the patients were subjected to FESS. In this
      study we found that the overall incidence of inflammatory disease in the
      osteomeatal complex in these symptomatic patients was no different between with
      and without Concha bullosa and osteomeatal complex disease is found to be more
      frequent if peumatization is localized to inferior part of middle turbinate.
      Concha bullosa requires specific endoscopic surgical techniques.

PMID- 23119620
TI  - The head shaking nystagmus.
AB  - The head shaking nystagmus is a sign of vestibular assymmetry. Its detection is
      simple office test useful for screening the patients with vertigo and
      dysequilibrium. Its nature defies its recording with electro-oculography and is
      simply observed under Frenzel's glasses. The direction of nystagmus is
      persistently directed away from the site of lesion and is not influenced by the
      compensatory adjustments. It is transient, rotatory and repeatable in nature. Its
      reliability is limited in face of the difficulty in its recognition. In presence
      of strong spontaneous nystagmus in the same face, it is not recognised easily. In
      the present study, its validity in peripheral disorders was 49.27% and 14% in
      central cases. There are limitations In earring out this test in situations of
      railed intracranial the tension, hence, its use in the latter cases is limited.

PMID- 23119621
TI  - Successful management of benign paroxysmal positional vertigo with the epley
      manoeuvre.
AB  - Benign paroxysmal positional vertigo is a recurrent, disabling disorder
      characterized by transient vertigo induced by changes in head position. Several
      non-surgical and surgical treatment procedures have been recommended as
      definitive treatment in this condition. Recent reports indicate a favourable
      response to a variety of non-invasive, easy to perform liberatory manoeuvres,
      often with a single treatment session. We report our experience with the Epley
      manoeuvre in which we obtained a 90% overall success rate which is comparable
      with results of similar recent studies.

PMID- 23119622
TI  - A clinico-pathological study of the role of allergy on larynx in children.
AB  - Laryngeal manifestation of allergy though less common than rhinosinusitis,
      tubotympanitis and bronchopulmonary allergy is not that uncommon and is usually
      misdiagnosed and mistreated in children. Hence, the importance of larynx as the
      allergic shock organ in children with spasmodic croup and laryngotracheo
      hronchits. In the present study, children below five years, presenting with
      Stridor and/or hoarseness were evaluated regarding the history of allergy, direct
      laryngoscopic finding, measurement of serum IgE,. presence of eosinophilia and
      histopathological examination of laryngeal biopsy. Out of the 80 cases studied, 9
      cases (11.2%) presented with associated allergic manifestation, 8 cases (10%)
      having family history of allergy. 4 cases (5%) having raised serum lgE, 12 cases
      (15%) with eosinophilia and 3 cases (3.75%) with eosinophilic infiltration on
      histopathological examination of the biopsy material taken during the direct
      laryngoscopy.

PMID- 23119623
TI  - Management of tongue base obstruction in obstructive sleep apnoea syndrome.
AB  - Studies have shown that the obstruction in OSA is more often than not
      multicentric. Tongue base obstruction is relatively more difficult to diagnose
      accurately and treat effectively. In this presentation, an effort is made to
      suggest two methods of management of this problem. One deals with the surgical
      management and the second, an alternative non-surgical method.

PMID- 23119624
TI  - Paraganglioma of nasal gavity.
AB  - Non - Chromaffin Paraganlioma arises in paraganglia of chemoreceptor system. It
      has been reported in the following sites-aortic bodies, superior vagal ganglion,
      auricular branch of vagus, inferior vagal nodose ganglion, superior laryngeal
      nerve, mandible, ciliary ganglion, bifurcation of pulmonary artery, pleura,
      femoral artery, pleura, femoral artery, retroperitoneal tissue, mesentry, coccyx
      and pineal body. Paraganglions of nasal cavity is a very rare occurance. A very
      few cases were reported before this.

PMID- 23119625
TI  - Rhinoscleroma- surgical management - a case report.

PMID- 23119626
TI  - Lupus vulgaris of nose - a case report.
AB  - Lupus vulgaris which is a mucocutaneous form of Tuberculosis is not an uncommon
      condi-tion. But the disease resulting in excessive destruction is rare today. We
      report a case of lupus vulgaris which almost completely destroyed the nose.

PMID- 23119627
TI  - Primary isolated nonhogkin's loymphoma of the tonsil -a case report.
AB  - Malignant lymphoma (Non-hodgkin's lymphoma) is a primary malignant tumor of
      lymphoid tissue composed of lymphocytic or reticulocytic derivatives of varying
      degree of differentiation. The tumor frequently occurs in the extranodal sites
      including the gastrointestinal tract and the Waldeyer's ring. Amongst the non
      Hodgkin's Lymphomas, the small cell type is the relatively uncommon lymphoma (4%)
      whereas others include follicular type (40%) and the high grade type (40-65%).
      This case report is of a case of primary isolated non-Hodgkin's lymphoma of the
      tonsil of small cell type.

PMID- 23119628
TI  - Rhabdomyosarcomas unusual nasal and pns presentation.
AB  - Rare cases of rhabdomyosarcomas are presented along with a review of medical
      literature. The clinicopathological aspects of the tumor are discussed. An
      attempt has been made to assess the biological behaviour, results of treatment
      and prognosis of these cases.

PMID- 23119629
TI  - A rare case of rhinoscleroma.
AB  - Rhinoscleroma is progressive granulomatous disease commencing in nose and
      eventually extending into the nasopharynx, oropharynx and sometimes lacrymal sac
      trachea and bronchi. This is a rare case of Rhinoscleroma presenting with
      complete nasal obstruction, and dysphagia. The lesion was involving the nose,
      palate, upper jaw, and lacrymal sac.

PMID- 23119630
TI  - A case report of esthesioneuroblastoma.
AB  - Esthesioneuroblastoma (Olfactory Neuroblastoma) arises from the olfactory placode
      in the olfactory area of the nasal cavity. The age incidence ranges from 3 years
      to 79 years. It usually presents with nasal symptoms like obstructed nasal
      breathing and epistaxis. The diagnosis may be delayed for several months due to
      its slow growing nature. It may be misdiagnosed with other small round cell
      tumors. One such case is reported here due to its rare incidence, difficulty in
      early diagnosis and very aggressive behaviour compared to the reported series
      inspite of recommended treatment by different modalities.

PMID- 23119631
TI  - Non apnoeic snoring-theoretical considerations.
AB  - A brief review of snoring with regard to the aetiology, patho-physiology,
      investigations and treatment is presented. Questions and unresolved issues are
      highlighted, hoping to point out directions towards future studies.

PMID- 23119632
TI  - Bilateral choanal atresia in adults - a rare presentation.
AB  - The occurrence of bilateral choanal atresia in adults is extremely uncommon. A
      case report of a 20-year-old male presenting with nasal obstruction due to
      bilateral osseous choanal atresia is discussed for its clinical interest.

PMID- 23119633
TI  - Basaloid squamous carcinoma of the nasal cavity - a case report.
AB  - Basaloid squamous carcinoma is a rare variant of squamous carcinoma and is known
      for its aggressive behavior. Its presentation in the nasal cavity is uncommon . A
      case of this tumor arising from the nostril and showing good response to
      concomitant radiotherapy and cisplatinum is presented.

PMID- 23119634
TI  - Foreign body in the pterygo - palatine fossa.
AB  - A rare case of long standing foreign body (part of a scissors blade) in the
      pterygo-palatine fossa producing trismus is reported for clinical interest.

PMID- 23119635
TI  - Empty sella syndrome.
AB  - A 55 year lady having severe attack of headache, vomiting & giddiness, diagnosed
      as acute attack of migraine & kept on prophylactic treatment of migraine -
      Propranolol- cipler after controlling the acute attack by emidixyn, vasograin &
      sarotena. On subsequent similar attack, X-ray skull lateral view showed enlarged
      sella. But ophthalmoscopy & visual fields were normal. There was no may sign of
      pituitary tumor, so it was diagnosed as empty sella syndrome. C. T. Scan of head
      confirmed it as empty sella.

PMID- 23119636
TI  - An unusual foreign body (10 N. P. COIN) in nasopharynx.

PMID- 23119637
TI  - Multiple foreign bodies (open safety pins) in the oesophagus.
AB  - Intra luminal hypopharyngeal and oesophageal foreign bodies are common. Among
      these the incidence of open safety pin is relatively uncommon and the occurrence
      of multiple open safety pins in the same ' individual is a very rare phenomenon.
      Removal of one open safety pin itself is a surgical enigma, as inadvertant
      attempts at removal may cause the pointed end to get impacted submucosally or
      intramurally or may cause oesophageal tear and calls for the assistance of a
      thoracic surgeon. This article intends to highlight the occurrence of multiple
      open safety pins in the lumen of the oesophagus and its difficulty in successful
      retrieval.

PMID- 23119638
TI  - A rare foreign body in the maxillary antrum.
AB  - A case of metallic foreign body getting impacted into maxillary antrum and orbit
      due to a blast in a furnace, presenting primarily with 20% facial burn & ocular
      symptoms is presented for its rarity.

PMID- 23119639
TI  - An unusual foreign body in the tracheobronchial tree.
AB  - Foreign bodies in the tracheobronchial tree are a common occurrence. But the
      incidence of broken parts of the tracheostomy tube as a foreign body has seldom
      been reported before. One such case is reported, where a patient presented with
      two occurrences of broken flanges of Fuller's tracheostomy tube enlodged in the
      tracheobronchial tree. The first presentation was indeed unusual when the broken
      components of the tube were found impacted in bilateral primary bronchi. After a
      period of 6 months, a similar episode recurred and at this time the right flange
      was found enlodged in the right primary bronchus. At both instances successful
      removal of the foreign body was possible. This case is being presented based on
      the peculiarity of the nature of the foreign body and involvement of both
      bronchi.

PMID- 23119640
TI  - Unusual foreign body (denture) in tracheo- bronchial tree.
AB  - Foreign bodies in aero-digestive tract have been reported over the years. A case
      of denture as a foreign body bronchus was reported to the department. We could
      find no evidence of denture being reported as foreign body bronchus & therefore
      this case is being reported.

PMID- 23119641
TI  - An unusual tracheal foreign body - a case report.
AB  - Foreign bodies in the laryngopharynx can occur without discrimination of age or
      sex. Their occurrence is influenced by mode of living, customs, habits and
      environment. T.M. Paramciwaran(1977) reported 56 cases of foreign bodies of
      tracheobronchial tree in the span of 5 years. A.S.A. Abdel-Salam and Alan G. Gibb
      (1980) mentioned that the vast majority of cases occur in young children. They
      have reported that undiagnosed foreign bodies cause mechanical effects, chemical
      reactions and may present as chronic pulmonary infection, allergic asthma,
      bronchiectasis, lung collapse or lung abscess. They present as emergencies and
      require skilful management.

PMID- 23119642
TI  - Endoscopic endonasal emergency management of bilateral choanal atresia in new
      borns.
AB  - The advent of the rigid paediatric nasal endoscope has revolutionized the
      management of congenital choanal atresia. This endoscopic endonasal approach is
      considered as a simple, safe and reliable procedure. Also, definitive surgery for
      choanal atresia has been quite a challenge especially regarding the fulfillment
      of two important objectives- complete removal of the atretic plate and assurance
      of wide long-term patency of the posterior nares. Several approaches to the
      posterior nares have been described in the past. These include: the transpalatal
      (English, 1981 and Owens,196S), transnasal (Singhl990 and Singh 1991),
      transseptal and transantral (Hall et al 1982 and Osquthorpe et al 1982)
      approaches. However, endoscopie endonasal surgery for choanal atresia is found to
      be better due to the simplicity of the surgery, better access and lesser
      morbidity. The objective of this presentation is to encourage the use of the
      rigid nasoendoscope in the management of cases of bilateral choanal atresia of
      the newborn.

PMID- 23119644
TI  - Ostiomeatal complex pathology versus maxillary sinus pathology: (How I Perceive
      it? - a reappraisal).

PMID- 23119643
TI  - Placement of prosthesis after total maxillectomy in edentulous patient.
AB  - It is very difficult to retain the prosthesis in edentulous patient after total
      maxillectomy as there are no teeth on the opposite side around which clasp can be
      applied, however if holes are drilled in obturator and in alveolar ridge and wire
      is passed through it, prosthesis can be retained satisfactorily.

PMID- 23119645
TI  - Foreign body bronchus - presenting with asthma.
AB  - Foreign bodies in the respiratory passages are always due to the accidental
      inhalation. Children are more affected while the adults rarely present with the
      foreign bodies in the respiratory tract. A case report of an accidentally inhaled
      foreign body ( a broken piece of a stainless steel spoon handle), where the
      patient was not aware of it and presented with bronchial asthma is being
      presented.

PMID- 23119646
TI  - Malignant melanoma of the nasal mucosa.
AB  - Malignant melanoma of the nasal mucosa is a rare tumor. We present here a case
      which involved the nose and the paranasal sinuses. Though surgical excision was
      achieved, postoperative metastalic spread to the liver resulted in poor
      prognosis, necessitating chemotherapy. Relevant literature on the subject is
      reviewed.

PMID- 23119647
TI  - Putative histogenesis of post nasal angiofibroma.
AB  - Inspite of the histological resemblance, these tumefactions do not behave like
      true neoplasms. Harma (1959) believed their histogenesis from angioblasls. Taxy
      (1977) regards the fihroblasts as the main stroma cell which has resemblences
      like those of the granulation tissues, and hence appear to be hybrid fihroblasts.
      Vascular and fibrous element could be produced by any mesodermal "stem cell"
      (Shenoi. 1989). Therefore both fihroblasts and angioblasts may be inter
      convertible.The cavernous element of tumour suggest it to be the hamartoma. The
      posterior part of nose and turbinates have very vascular and cavernous mucosa.
      The hamartomas are influenced by endocrine factors and growth hormones. The
      mesodermal element of this tumour also appear to have androgen receptors (Lee et
      al, 1980). These endocrine factors could be the initial triggering mechanisms,
      for their development appear most rapidly at the parapubertal age. The tumour is
      also influenced by peri-and apocrine factors. The eytogenic growth factors are
      locally available. The neoangiogenesit is, perhaps, influenced by these factors,
      which also induce destruction of basement membrane of vessels, migration and
      mitosis of angioblasts and formation of new blood vessels of capillary and larger
      sizes. The maturation of tumour appears to he heralded by reduction in endocrine
      factor tike growth hormone and establishment of sex hormones beyond the puberty.
      Further it is accelerated by local peri-and apocrine factors contributed by
      macrophages, lymphocytes etc. Those cases with heavy infiltration, therefore,
      have more often the signs of maturity like collagenisation, encapsulation,
      obliteration of vascular elements and necrobiotic phenomenon. These are
      exceptional tumours estntially observed amongst para-puberal males, having easy
      bleeding tendency and multidirectional extensions. They destroy the hones of
      skull and occupy adjoining cavities including cranial extensions in almost 20%
      cases (Ward et al, 1974). There is high recurrence rate (20 to 50% after initial
      excision). There are different views regarding their aetiopathogenesis, but none
      is able to explain all its features. These are considered to be inflammatory or
      allergic in origin (Willis, 1953), hyperplastic tissue reactions (Harma, 1959),
      due to androgen deficiency (Martin et al., 1948), vascular malformation
      (Osborn,1959) and hamartomas (Mishra & Bhatia.1964). Lately, micro-histological
      and marker techniques and better understanding of oncogenesis, have been
      available which give more insight in explaining its behaviour. In view of
      controversies, a retrospective study of more than 300 cases of angiofibromas is
      carried out to formulate a putative pathogenesis of this tumour and its peculiar
      behaviour.

PMID- 23119648
TI  - Incidence of fungal infections in chronic maxillary sinusitis.
AB  - Fifty patients with chronic maxillary sinusitis were included in our study.
      Antrat aspirate of chronically inflamed maxillary sinuses collected by antrat
      puncture were subjected to fungal culture. The study revealed the presence of
      fungi in 3 cases. Aspergillus fumigatus was isolated in 2 cases while Candida
      albicans was found in 1 case. The role of fungi, particularly aspergillus as
      pathogen is discussed in the context of antibiotics and immuno-suppressive
      therapy and local predisposing factors.

PMID- 23119649
TI  - A Correlative study of sinusitis versus headache.
AB  - Headache is a very annoying condition for patients and also for those trying to
      tread it.Head aches can be of sinugenic origin, even if this cause may not be
      suspected from the case history:Average age of onset for sinugenic headache is 25
      to 30 years. Sinugenic headache occurs equaliy in both saxes. Diagnosis of
      sinugenic headache is done by the clinical history,examition of nuse and
      paranasal sinuses and relevant investigatins besides excluding the headaches of
      nonsinugenic and pyschogenic cause. Surgical treatment is helpful in curing the
      patients of sinugenic headaches in most of the cases. Only two patients could
      benefit with medical treatment. Recurrences are common in patients of headaches
      of multiple etiology and more if not treated specfically.

PMID- 23119650
TI  - The particle repositioning maneouvre for benign paroxysmal positioning vertigo.
AB  - Thirteen consecutive cases wherein Benign Paroxysmal Positional Vertigo was
      diagnosed are retrospectively reviewed. The Dix-Hallpike positioning test was
      classically positive with a typical torsional, down beating, transient nystagmus
      in four of these thirteen cases. The diagnosis in the other nine was based on a
      suggestive history with or without subjective vertigo on the positioning test.
      Ten cases improved with labyrinthine suppressants and habituation exercises
      alone. This included all the patients wherein the Dix-Hallpike maneouvre did not
      elicit any nystagmus. However, in the group wherein the Dix-Hallpike maneouvre
      resulted in nystagmus, only one of the four improved and the particle
      repositioning maneouvre (PRM) was employed in the three cases with persistent
      symptoms. Two had immediate relief of symptoms. The particle repositioning
      maneouvre was repeated after three days in the one other patient and proved
      successful on this second occasion. Surgical treatment was not necessitated in
      any case, It is proposed that the particle repositioning maneouvre should be the
      preferred first-line treatment for any patient who on Dix-Hallpike testing
      demonstrates nystagmus typical of BPPV.

PMID- 23119651
TI  - Nasal endoscopy-evaluation in epistaxis.
AB  - Epistaxis is generally of two types : one where a cause is recognised ( Local or
      Systemic ) and the other where the cause is not known. All cases of nose bleeds
      with no evident cause is customarily categorised into an Idiopathic type.
      Anterior rhinoscopy ordinarily gives a very limited view of the nose and the
      probable cause of epistaxis, and this, we feel could he one of the reasons why a
      proper diagnosis is not always likely. Another problem is the poor localisation
      of the site of bleeding point. Such cases pose a problem in implementing
      treatment, as the cause or the site is not easily located. This study tries to
      venture the exquisite and wide vision provided by the Nasal endoscope. This study
      also tries to investigate the possibility of reaching the inaccessible bleeding
      points, to treat them directly. The study was conducted on 60 patients who
      attended the Out Patient Department and the Indoor ward with complaints of
      Epistaxis.

PMID- 23119652
TI  - Fine needle aspiration cytology(fnac) versus hlstopathology in cervical
      lymphadenopathy.
AB  - The present series includes 104 cases (36 males and 68 female) of lymph node
      swellings in the head and neck region in the mean age group of 30.6 years. The
      aspiration cytology was carried out as an outpatient department procedure and
      concomittant biopsy was performed in all the cases of this series. The overall
      diagnoitic accuracy rale of FNAC in the present histopathologically proved cases
      was found to be 92.3 percent. In 8 out of 104 cases (7.7 percent), the smears
      were unsatisfactory and therefore diagnosis could not be made by mere cytological
      examination.

PMID- 23119653
TI  - Nasal dysfunction amongst divers during bounce and saturation diving.
AB  - 5O divers were subjected to detailed pre and post dive examination to study the
      effect of barotrauma. The various sinunasal pathologies which were detected are
      discussed and the significant difference seen between bounce divers, saturation
      divers and control group of diving recruits is highlighted.

PMID- 23119654
TI  - Tuberculous otitis media-are we missing it ?
AB  - Tuberculosis of the middle ear it a rare disease. Due to change in the typical
      clinical pattern and decrease in incidence, there is a delayed or missed
      diagnosis and can lead to increased morbidity. We pretent 5 cases of Tuberculous
      Otitis Media treated over a period of 2 years, highlighting the fact that it must
      be considered as a differential diagnosis of persistent suppurative otitis media.

PMID- 23119655
TI  - Results of KTP-532 laser and tendon preservation stapedotomy in otosclerosis-a
      preliminary report.
AB  - Tendon preservation stapedotomy with or without KTP-532 laser has been performed
      on 25 rases Jrom November 1998 to February 2000. A study of the symptoms,
      demographic profile, audiological impairment, surgical treatment and the
      resultant hearing improvement after 3 weeks and 6 weeks was done. KTP-532 laser
      assisted cruratamy and stapedotomy was found to be easier than the conventional
      method. Insertion of the prosthesis was also found to be much easier because of
      tendon preservation.

PMID- 23119656
TI  - Management of acute vertigo with betahistine.
AB  - This open, prospective study was carried out in 29 outpatients of vertigo with
      Betahistine treatment at a dose of 16 mg three times daily far a maximum
      treatment period of 6 weeks or earlier until remission of vertigo attacks. The
      evaluations were carried out based on three parameters such as frequency,
      duration, and severity of vertigo attacks. Betahistino showed a significant
      improvement in the three parameters of frequency, duration and severity of
      vertigo attacks. Associated symptoms such as tinnitus, nausea, vomiting,
      headache, faintness showed a significant improvement with the therapy. Subgroup
      analysis showed a significant improvement of patients with severe and
      incapacitating verlign attaeks at baseline. Thus, this study proves excellent
      efficacy and goad tolerability of Betahistine as an anti-vertigo drug at a dose
      of 16 mg three times daily and gives a new insight for controlling acute or
      severe vertigo attacks without causing sedation.

PMID- 23119657
TI  - Quincke's oedema of the uvula associated with mucous retention cyst-a case
      report.
AB  - We report a rare case of recurrent angioedema of uvula (Quincke's Oedema),
      causing air way obstruction. A brief review of literature and treatment options
      are alto included. The histoloigical specimen showed an associated mucous
      retention eyst, which in conjunction with Quinckc's oedema has not been
      previously reported.

PMID- 23119658
TI  - Neurofibroma of the posterior pharyngeal wall.
AB  - Benign tumours of the hypopharyx are exceedingly rare. A case report of a 53 year
      old male who presented with a neurofibroma of the posterior pharyngeal wall
      having complaints of muffled voice and dysphagia is presented for its clinical
      interest.

PMID- 23119659
TI  - Alveolar rhabdomyosarcoma of paranasal sinus with cervical metastasis-a case
      report.
AB  - Rhabdomyosarcoma (RMS) is a rare tumour in adults and involvement of paranasal
      sinuses is extremely rare comprising only 1.5% of reported head and neck
      rhabdomyosarcomas. Alveolar type, a rarer form of RMS, mainly seen in adults, has
      the worst prognosis. Incidence of lymph node metastases is more common in this
      type, compared to the other forms. An aggressive combined modality of treatment
      has dramatically improved the poor survival statistics noted previously. Our
      experience with one such case occurring in paranasal sinus and orbit which was
      managed by surgery multidrug chemotherapy & radical radiotherapy is discussed and
      relevant literature has been reviewed.

PMID- 23119660
TI  - An unusual cause of stridor-a case report.
AB  - Slridor in children is usually acute in onset and most commonly caused by
      infections such as acute laryngitis, laryngotracheobronchitis, and acute
      epiglottitis. Stridor due to foreign body is also not uncommon. The case reported
      is that of a large upper thoracic pre and paravertebral abscess presenting with
      stridor. Although a rare cause, it presents as a life threatening entity
      requiring urgent treatment.

PMID- 23119661
TI  - Angiolymphoid hyperplasia with eosbvophilia-case report.
AB  - Angiolymphoid hyperplasia with eosinophilia (ALHE) is a benign condition
      characterized by subcutaneous lesions in the head-neck region. It is frequently
      misdiagnosed as a malignant lesion. Knowledge of the existence of the disease and
      pathological interpretation are requisites for early diagnosis. We present a case
      report and review of the literature.

PMID- 23119662
TI  - A rare case of haemangioma of the tympanic membrane and external auditory canal.
AB  - An unusual ease of haemangioma of external auditory canal in a 16 yrs. old male
      is documented for its rarity.

PMID- 23119663
TI  - Lipoid proteinosis (urbach wiethe disease)-A case report.

PMID- 23119664
TI  - Nasopharyngeal rhabdomyosarcoma.
AB  - Nasopharyngeal Rhabdomyosarcama, a common soft tissue sarcoma in children, is a
      rare identity, only four cases so far have been reported as per the review of
      literature. Ours is the fifth case presented exclusively in the nasopharynx,
      which is reported, hereby. The prognosis of this clinical entity is always gloomy
      and the modality of thr treatment is always surgery, chemotherapy and
      radiotherapy.

PMID- 23119665
TI  - Bilateral acquired meatal atresia.
AB  - A case of bilateral acquired meatal atresia in a 3 year old male child with past
      history of bilateral otarrhoea is reported. Plain high resolution axial CT scan
      of temporal bones showed normal middle and internal ear structures bilaterally.

PMID- 23119666
TI  - Fibromyxoma larynx-emergency management.
AB  - Laryngeal tumours are not uncommon. Great majorities of cordal benign tumours are
      non-neoplastic. The important tumours are polyps and nodes, cysts, non-specific
      granulome of vocal process, papillary keratosis, laryngocoele and primary
      amyloiosis. These are mostly non-neoplostic tumours. Papiloma, Fibroma, Angioma,
      Chondroma, Adenoma, are the other varieties of laryngeal tumour which are
      neoplastie. Fibroma is mostly seen at the junction of middle and anterior thirds
      of the vocal lords. Fibromyxoma is a rare variety and can be confirmed by
      histopathology. Myxomatous tissue is invariably interspersed between fibrous
      tissue in fibromyxoma and their treatment is by complete endoscopie removal
      (Micro Laryngeal surgery) under anaesthesia.

PMID- 23119667
TI  - Nasopharyngeal angiofibroma-an unusual origin & presentation.
AB  - Case report presenting an unusual site of angiofibroma is described. An adult
      male presented with a mass hanging out from the right nostril with epistaxis. A
      C.T. scan performed in this cast described it to be an infected polyp. The
      patient was operated upon. The mass arose from the septum and bled on removal.
      The histopathological diagnosis of the mass showed characteristic features of an
      angiofibroma.

PMID- 23119668
TI  - Desmoid tumor (aggressive fibromatosis) of the neck.
AB  - Desmoid tumors are histologically benign fibrous neoplasms arising from the
      musculoaponeurotic structures throughout the body. There is similar biological
      behaviour between benign fibrous proliferations and fibrosarcoma. These neoplasms
      have the tendency to locally invade and erode adjacent muscular tissue and bone.
      Within the head and neck area they also tend to encase vital structures. We
      present a case of a 28-year-old white female with a five-month history of a
      painful mass in her left posterior cervical triangle who was treated by
      excisional biopsy of the lesion with preservation of the accessory nerve and post
      operative radiation. The histopathologic characteristics of desmoid tumors and
      treatment of these lesions are also reviewed.

PMID- 23119670
TI  - Tonsilloliths.

PMID- 23119669
TI  - How i do it.

PMID- 23119671
TI  - Post stapedotomy hyperacousis-A mechanical explanation.
AB  - Mechanical explanation for the hyperacousis that sometimes occurs after
      stapedectomy or stapedotomy is presented.

PMID- 23119673
TI  - An alternative light system for the micro-laryngoscope.

PMID- 23119672
TI  - Sarcomatoid carcinoma of larynx.
AB  - Surcomatoid Carcinoma are rare lesions reported in many organs including the
      larynx. This report describes such a mixed tumour occuring in the larynx. The
      clinico pathological features and treatment are described.

PMID- 23119674
TI  - Effect of a few histamine(1)-antagonists on blood glucose in patients of allergic
      rhinitis.
AB  - Histamine(1), receptor antagonists are being prescribed frequently in ENT
      practice. However, previously we found a fall of blood glucose with terfenadine
      and astemizole. Present study (double blind, randomized, single dummy and placebo
      controlled) evaluated the chronic effect (7 days of use) of clemastine,
      Loratidine and Certrizine on blood glucose level in patient of allergic rhinitis.
      Cetrizine produced a significant increase in post-prandial blood glucose (P<0.02)
      and a little rise in fasting blood glucose. Clamastine caused a little fall of
      fasting and a little rite of post-prandial blood glucose levels. The exact
      mechanisms involved in the effect of these drugs on blood glucose remain to be
      elucidated.

PMID- 23119676
TI  - Hygrometeric method-an important aid in nasal investigations.

PMID- 23119675
TI  - Lipomata of the pharynx.
AB  - Two rare cases of lipomata arising from the pharynx are being reported. The
      tumors were excised and have showed no recurrence.

PMID- 23119677
TI  - Orienting ourselves towards prevention & early identification of deafness.

PMID- 23119678
TI  - Otology - past, present and future.

PMID- 23119679
TI  - Role of ginkgo biloba extract in acquired sensorineural hearing loss.
AB  - The present study is on 52 patient of acquired SNHL who were treated with Ginkgo
      biloba extract (Ginkocer) or conventional treatment (Neurobion, Arlidine & Vit 
      A) or both. The age range was 11-75 years with male: female - 3.1. Commonest
      probable etiology was presbyacusis (36.5%) followed by idiopathic (28.8%).
      Subjective improvement in hearing was comparable in both the ttreatment groups.
      Objective improvement (> 10 dB ) was seen with Ginkocer therapy only in cases of
      idiopathic (3). ototoxicity (1) head injury (1). It was maximum in <25 yrs. age
      and ranged between 11-50 dB. However, statistically it was not significant for
      age, sex, socioeconomic status, oral habits, Hb level, serum cholesterol and
      albumin: globulin ratio. Patients showing no effect of drug were almost
      comparable in both the groups. In conventional group the remaining patients
      demonstrated drug efficacy of 30% while in the Ginkocer group it was upto 60%.
      The mean improvement in tinnitus was 52.32% with Ginkocer and 50.09% with
      conventional treatment. Relative improvement with Ginkocer was found better by
      15.56%, 21.94% & 9.09% in presbyacusis, idiopathic: and ototoxicity group as
      compared to conventional group.

PMID- 23119680
TI  - Role of microrhinoscopic sinus surgery in chronic sinusitis: Initial results.
AB  - Chronic sinusitis with/ without polyposis account for the majority of nasal
      pathology. The advent of Functional Sinus Surgery has led to a better
      understanding of the complex anatomy of the paranasal sinuses and the surrounding
      vital structures. The application of surgical principle and technique of
      Functional Endoscopic Sinus Surgery to another approach for regional pathology
      using operating microscope has enabled us to significantly refute this technique
      of treatment of sinus pathology namely Microrhinoscopic Sinus Surgery (MRSS). In
      this paper the technique as well as the initial results of the Microrhinoscopic
      Sinus Surgery(MRSS) is discussed with its advantages.

PMID- 23119681
TI  - Brain stem evoked responses in patients with diabetes mellitus.
AB  - Diabetes mellitus is a systeihic disorder which targets multiple organs. The
      neurological involvement is not only in the form of peripheral neuropathy, but
      may also lead to central neuropathy. To evaluate the presence of central
      neuropathy auditory brain stem evoked responses were recorded from 25 normal
      hearing diabetic subjects aged 28 years to 49 years (Mean age 44.28 years) at
      2KHz, 4KHz, & 4KHz, frequencies. The results obtained were compared with those
      obtained from 10 subjects with normal hearing of matched age and sex. In diabetic
      subjects, abnormal wave latencies were correlated with blood glucose level,
      duration of illness and peripheral neuropathy.The absolute latencies and inter
      peak latencies were significantly impaired (P<.001) in diabetic subjects as
      compared to control subjects at 2, 4, & 6KHz frequencies. The incidence of
      delayed wave latencies was 64%, 72%. & 84% at 2KHz, 4KHz, & 6KMz respectively
      suggesting that if brain stem evoked response audiometry is conducted at higher
      frequency like 6KBz in diabetic patients, the involvement of central neural axis
      can be detected earlier. This study is the first to demonstrate that brain stem
      evoked response audiometry is a useful non-invasive test for earlier detection of
      damage in central neural axis in patients of diabetes mellitus. There is no
      relationship between the delayed wave latencies and the blood glucose level,
      however there exists a significant relationship between the delayed wave
      latencies and the duration of disease & peripheral neuropathy.

PMID- 23119682
TI  - The clinical radiological and histological correlation of orbital assessment in
      malignant lesions of the maxillo-ethmoid complex.
AB  - Twelve patients undergoing surgery between May 1995 and March 1999 for malignant
      tumours of the paranasal sinuses abutting or invading the orbital walls were
      studied for the need to remove orbital contents. Alt patients were evaluated
      clinically, radiologically (CT Scan) and per-operatively to delineate the extent
      of orbital invasion. Combined regimen (Surgery + Radiotherapy) were used in all
      patients. A biopsy from periorbita was taken when eye was spared. It was found
      that per-operative evaluation of the orbit is equally specific in comparision to
      clinical and CT Scan combined and eye may be preserved in selected patients with
      involvement of orbital periosteum provided there is no frank soft tissue mass in
      the orbit.

PMID- 23119683
TI  - Orbital cellulitis revisited.
AB  - Twenty patients with orbital cellulitis were treated over a seven-year period.
      All patients had a CT scan for localization and categorization of the disease.
      Fourteen of sixteen patients with post-septal involvement underwent surgical
      drainage and orbital exploration via an external ethmoidectomy approach. Two of
      these fourteen patients also had an optic nerve decompression. Clinical signs
      were found to be accurate in differentiating pre-septal from post-septal
      cellulitis tut were inadequate for further categorization of the type of post
      septal cellulitis. All ten patients with pre-septal cellulitis or a post-septal
      subperiosteal abscess recovered with preservation of vision. Mild to moderate
      degrees of visual loss could be reversed with emergent surgical treatment even
      after 10 days from the onset of visual loss. Post-septal intraperiosteal orbital
      cellulitis and orbital abscess however resulted in significant permanent visual
      disability in eight of ten cases.

PMID- 23119684
TI  - A clinical study on congenital and neonatal deafness.
AB  - Clinical and audiological assessment of seventy children with congenital and
      neonatal deafness Were analysed. Risk factor identification were emphasised.
      Dysmorphic features and syndromes were analysed.

PMID- 23119685
TI  - A comparative study in the management of auricular pseudocysts.
AB  - Pseudocysts of the pinna, commonly called seroma are an asymptomatic condition of
      unknown etiology affecting the pinna, commonly encountered in middle aged men.
      Prevention is practically impossible as etiology is unknown. However, early
      recognition and treatment are stressed.In our prospective study of 30 eases we
      compared the different treatment modalities available namely, wide bore needle
      aspiration, intracavitary steroid injection and window (de-roofing) procedure.
      Amongst them, the window (de-roofing) procedure was found to be successful in
      109% of the cases to prevent recollection of serous fluid with a minimum of
      sequelae.

PMID- 23119686
TI  - Role of lateral neck dissection in cancers of the larynx and hypopharynx with
      N(o) neck.
AB  - Radical neck dissection is a standard procedure carried out for the teatment of
      palpable nodes in the neck but if carried out electively in cases where there are
      no palpable nodes in the neck it is considered to be an overtreatment with its
      associated morbity. Lateral neck dissection was carried out on twenty patients
      who had T31 T4 lesion of the larynx and hypophar-vnx with NO neck. The dissection
      entails removal of Level II. III and IV nodes. Occult metastasis 80% and 85%
      respectively. The mean follow up was 13 monts. It appears from our study that
      elective lateral neck dissection is a promising and safe procedure and may be
      useful as an important prognostic tool in sampling the lymph nodes and predicting
      recurrences in the neck.

PMID- 23119687
TI  - Vagal origin of the ANSA cervicalis nerve - report of two cases.
AB  - Ansa cervicalis is a loop of nervers usually by C1, C2 and C3 fibres in the
      lateral aspect of the neck, Occasionally the superior root of the ansa (derived
      from C1) may original from the vagus either party or entirely, but the fibres can
      be traced back to their true cases of ansa cervicalis arising from the nagal
      trunk observed in dissection room cadavers is described here. Since the ansa
      cervicalis is frequently used in reinnervation of the paralyzed larynx, awareness
      of such a variation will be of use to the surgeon during a surgical procedure.

PMID- 23119688
TI  - Recurrent metastasi zing neuroendocrine tumor of paranasal sinuses.
AB  - Neuroendocrine tumours- their rare occurrence and propensity for recurrences can
      undoubtedly pose as a diagnostic and therapeutic dilemma. A case report of one
      such case with recurrence and bony metastasis is presented.

PMID- 23119689
TI  - Toxoplasmosis as a rare cause of symptomatic cervical lymphadenopathy.
AB  - Cervical lymphadenopathy due to several different actiologies is commonly seen in
      Otorhinolaryngologie(ENT) clinies. Toxoplasmosis is one of the rare causes of
      cervical lymphaden-apathy although it is not true the other way around as
      lymphadenopathy is not rare in the cases of toxoplasmosis. It is even rarer for
      the toxoplasmic lymphadenopathy to be symptomatic. The case presented here
      becomes more interesting as it unusual to see affection of anterior cervical
      lymph nodes rather than the posterior group which typically gets involved in
      Toxoplasmosis. Over view of the literature has also been discussed.

PMID- 23119690
TI  - Traumatic retropharyngeal abscess presenting with quadriparesis: A case report.
AB  - Retropharyngeal abscess is not very common in adults. If it occurs,it is usually
      secondary to tuberculous lesion of spine or penetrating forgein body in food
      passage. We describe a case of retropharyngeal abscess with quadriparesis
      following neck trauma.

PMID- 23119691
TI  - Extrathoracic castleman'S disease - presenting as a neck mass.
AB  - Castleman's disease, also known as angiofollicular hyperplasia, is a disease of
      unsettled complexity and morbidity, usually occurs in the mediastinum and less
      frequently in the neck as a solitary mass and is often associated with other
      illnesses. Two variants have been recognized, the hyaline vascular type which is
      mare common and the less common plasma cell type with a third hybrid or
      intermediate type that shares features with both. It has been described with AIDS
      and Kaposi's sarcoma as well as follicular dendritic cell tumours.We report a
      case of Castleman's disease of the hyaline vascular type arising in the left
      supra-clavicular region in 41 year old male without any associated systemic
      illness. The neck is an uncommon location for this rare disease.

PMID- 23119692
TI  - Fronto-ethmoidal mucormycosis - a case report.
AB  - A fifty year-old female patient suffering from Mucormycosis of fronto-ethmoidal
      region wot successfully treated by surgical debridement and oral antifungal
      therapy.

PMID- 23119693
TI  - Benign cementoblastoma - a rare odontogenic neoplasm.
AB  - Benign Cementoblastoma is a rare cementum producing tumour of odontogenic origin
      having very characteristic clinical features and radiological findings. A rare
      case of Benign Cementoblastoma is presented here for clinical interest.

PMID- 23119694
TI  - Histiocytosis of the temporal bone.
AB  - Histiocytosis is a rare disease of unknown aetiology which commonly affects the
      head and neck region. In the ear it can closely mimic acute and chronic ear
      disease leading to a confusion in diagnosis. It can be easily misdiagnosed unless
      a high index of clinical suspicion is maintained. We present a case of Letterer
      Siwe disease of the temporal bone which presented with bilateral mastoid
      abscesses.

PMID- 23119695
TI  - Rosai dorfman disease - an unusual presentation: A case report.
AB  - Rosai Dorfman Disease (Sinus Histiocytosis with massive lymphadenopathy) is a
      rare self-limiting histiocytic disorder of unknown etiology usually presenting
      with cervical lymphadenopathy and haematological abnormalities. Extra-nodal
      presentation is rare . This ease is such a rare presentation of Rosai Dorfman
      Disease.

PMID- 23119696
TI  - Heusinger-s syndrome-a case report.
AB  - Heusinger's syndrome or Branchio-oto-renal dysplasia is a rare congenital
      anomaly. One such case with external ear anomalies, branchial fistula and renal
      abnormality is presented. The patient underwent successful excision of the
      branchial fistula. The case is discussed with review of relevant literature.

PMID- 23119697
TI  - Rhinosporidiosis on HIV - a case report.
AB  - Rhinosporidiosis is a chronic disease that classically presents with the
      involvement of nose and nasopharynx. However, it can be present in various other
      sites including conjunctiva, vulva, vagina, larynx and scalp. We report a case
      with a Rhinosporidial mass in the nose extending to oropharynx and multiple
      cutaneous lesions of Rhinosporidiosis in a patient with HIV, This case is the
      first of its kind where HIV has been associated with Rhinosporidiosis.

PMID- 23119698
TI  - Tonsillar lymphangiomatous polyp - a case report.
AB  - Tumors which are benign in origin in palatine tonsils are not uncommon. They may
      create anxiety in patients and pose difficulty in differentiating from
      malignancy. We report a case of tonsillar polyp of lymphangiomatous origin.

PMID- 23119699
TI  - Solitary extramedullary plasmacytoma of tonsil - a rare location.
AB  - Extramedullary plasmacytoma is a rare form of plasma cell dyscrasia, in which
      plasmacell tumours arise outside the bone marrow. The tumor may arise in any part
      of the body but the vast majority occur in head and neck, primary in the nasal
      cavity, paranasal sinuses or upper airway. We present here a rare case of
      extramedullary plasmacytoma arising from the tonsil The clinical,
      histolopathology, immunohistochemical findings are reviewed and the management
      discussed.

PMID- 23119700
TI  - A giant pedunculated tumor (Fibrolipoma) of oesophagus - a rare case.
AB  - A giant pedunculate tumour of oesophagus is reported in this study for its
      rareness.A mate patient aged 48 years was admitted at Jorhat Christian Medical
      Centre with the complaint of swelling of the neck and dysphagia for a period of 4
      months. Clinically the neck swelling looks like swelling of left lobe of thyroid
      with intrathoracic extension, ENT examination was normal The barium Swallow X-ray
      of oesophagus showed surprisingly huge dilatation of upper half of the
      oesophagus. The oesophagoscopy snowed a large mobile infra oesophageal tumour
      extending from the upper end of the oesophagus upto the mid thoracic region. The
      neck is explored by collar incission and the cervical oesophagus is opened by
      longitudinal incission. The tumour is pulled out from the oesophagus and is
      removed completely by cutting the peduncle which was attached to the tight wall
      of the oesophagus just below the cricopharynx. The peduncle was about I em in
      diameter., The length of the tumour was about 3-4 cm at the thoracic part. Post
      Operative recovery was uneventful. The histopathology report skewed it to be a
      ease of FIBROLIPOMA.

PMID- 23119701
TI  - Prognoma of maxilla.
AB  - Prognoma is a rare dysembryogenic tumour of infancy Very few cases have been
      recorded in the world literature so far A case report of this tumour affecting a
      female child with involvement of the right maxilla is being presented
      Histopathologically prognoma is a melanotic neuroectodermal tumour An increased
      level of a-fetoprotem m the serum and vanillylmendilic acid (V M A ) in a 24
      hours urine sample have been reported with prognoma.

PMID- 23119702
TI  - Foreign body nose - an unusual presentation (Short Communication).
AB  - Foreign bodies in the ear and nose are commonly encountered in children. Adults
      more commonly present with foreign bodies in the ear like cotton plug or
      matchstick piece. A 20 year old male presented to our emergency with history of
      accidental injury with a air gun and suspicion of a metallic pellet in the nose.
      A ease report is presented.

PMID- 23119703
TI  - Benign symmetrical lipomatosis (Madelung'S disease).
AB  - A case of benign symmetrical lipomatosis of neck in a 10 year, thinly built child
      is presented with outline of possible etiology and treatment. Since this disease
      barely finds mention in otolaryngotogy textbooks, although these patients usually
      first present to olotaryngologists, this case is reported to make aware the young
      fraternity with the disease entity.

PMID- 23119704
TI  - Extensive squamous cell carcinoma involving the parotid gland and carotid artery
      a case report.
AB  - Squamous cell carcinomas of the parotid gland are very rare. Majority of them
      will be metastatic with primaries in the head and neck. Very rarely, they can be
      from unknown primaries or primary parotid tumor itself. We present a case of the
      Squamous cell carcinoma with extensive local spread to the scalp, skin of the
      face, parapharyngeal space and causing occlusion of the internal carotid artery.
      Brief review of literature regarding primary and secondary type of these tumors
      is also included. Key words: Squamous cell carcinoma, parotid tumors.

PMID- 23119705
TI  - Paranasal sinus aspergilloma: a case report.
AB  - Aspergilloma, though rare, is a benign condition of the paranasal sinuses
      affecting young males with reasonable morbidity. Besides diagnosis, optimal
      surgery and prolonged adequate medical therapy under vigilant supervision is
      mandatory to treat this condition effectively, We are presenting one such ease of
      aspergilloma who was appropriately managed.

PMID- 23119706
TI  - Kimura's Disease - report of a case masquerading as a parotid tumor.
AB  - Kimura's Disease is a part of an ill- defined spectrum of vascular lesions of the
      subcutis. It is a benign chronic inflammatory condition producing subcutaneous
      tumour like nodules chiefly in the head and neck region with predilection for
      periauricular areas. It is characterised histologically by dense fibrosis,
      lymphoid infiltration, vascular proliferation and eosinophilia. The condition has
      a preponderance in the for eastern countries. It is extremely uncommon in Indian
      subcontinent. There has been no reported case from the Indian subcontinent in the
      English Literature. We report such a rare case in which the condition presents as
      parotid masses. We also present its CT, MRI & histopathology features and a brief
      review of literature.

PMID- 23119707
TI  - Arterio venous malformation with auricular hypertrophy.
AB  - We report a case of arterio-venous malformation (AYM) of the external ear with
      hypertrophy in a 25 years old male which had been stable for many years, only to
      expand following trauma, with occasional bleeding episodes. Surgical correction
      and plastic reconstruction without proximal ligation of the feeding arterial
      system was contemplated.

PMID- 23119708
TI  - Tonsillar carcinoma - a review.
AB  - Tonsillar carcinoma which is a not uncommon form of head-neck malignancy is
      reviewed.

PMID- 23119709
TI  - Computer-assisted functional endoscopic sinus surgery (c-a fess) - a review.
AB  - CT and MR imaging give spatial information of patient's disease and anatomy. They
      help in preoperative surgical planning and guide the surgeon during operation. In
      conventional Functional Endoscopic Sinus Surgery (FESS), surgeon mentally
      correlates the information of CT and MR with the direct sinuscopic view of
      operative field. In Computer-Assisted Functional Endoscopic Sinus Surgery ( C-A
      FESS), computer provides image guidance for the surgeon. Surgeon can appreciate
      ike immediate surrounding structures outside the direct endoscopic vision of the
      surface. Thus widely enhancing the field of endoscopic mage. The overall accuracy
      of 1 to 2 mm has been reported. Many systems of tracing are being developed and
      tested far. Each system has its own advantages and disadvantages. It is now
      possible to guide mrgery with intraoperatively acquired MR images. The real-time
      imaging shows the tissue changes occurring during the operation. Surgeon can
      safely operate the lesions of optic nerve, sphenoid sinuses, pituitary gland, and
      cranial base.

PMID- 23119710
TI  - Laryngotracheal stenosis & pharyngocutaneous fistula in cut-throat injuries - how
      we managed them.
AB  - Two successfully treated cases, one of laryngotracheal stenosis & another of
      pharyngocutaneous fistula have been presented. These complications developed due
      to bad initial management & poor physical health following cut-throat Injury, It
      was observed that cheaper stents like polythelene endotracheal tube gave good
      remits like costlier stents in the treatment of stenosis. Mild degree of
      subglottic stenosis could he dilated to yield good airway thus avoiding major
      surgery.It should be remembered that proper initial management & early repair of
      the 'cut-throat injury' would avert these complications.Post-operative follow-up
      for at least a year & more is mandatory to assess the final outcome.

PMID- 23119711
TI  - Annular bony spur.
AB  - A micro anatomical feature in the ear useful in surgery is described.

PMID- 23119712
TI  - Cystic hygroma: Presentation of two casfes with a review of the literature.
AB  - Two interesting cases of cystic hygroma are being reported. One presented with
      dyspneoa and the other one with macroglosia and mediastinal cystic hygroma. The
      foetal chromosomal anomalies associated with cystic hygroma, intrauterine
      diagnosis and treatment of cystic hygroma as well as pathogenesis,
      classification, surgical and non-surgical management of cystic hygroma has been
      discussed in detail in the review of the literature.

PMID- 23119713
TI  - Nasopharyngeal presentation of renal cell carcinoma.
AB  - In this case report, we present a 50-year- old woman, who presented with severe
      headache as her only presenting clinical symptom due to nasopharyngeal mass.
      Histo-pathological evaluation of the biopsy from nasopharyngeal mass revealed
      clear cell carcinoma. On further evaluation, an asymptomatic mass was detected in
      the left kidney. The metastatic lesion was treated with palliative radiotherapy.
      A search of the literature revealed no reports of such unusual metastasis in the
      nasopharynx from a primary carcinoma of the renal origin.

PMID- 23119714
TI  - Alkathine shell, an innovative way of neck flexion after tracheoplasty.
AB  - Tracheal resection and end-to-end anastomosis is the treatment of choice for
      mature, isolated, segmental tracheal stenosis and tracheomalacia.
      Postoperatively, it is important to avoid tension at the anastomotic site. This
      is usually done by keeping the head in flexion, by a skin suture from chin to
      chest in the midline. Movement in the post-operative period often results in
      cutting through of this suture and also formation of scar tissue at the suture
      site, particularly in those prone to keloid formation. We report seven cases with
      tracheal stenosis who had primary repair and were managed postoperatively without
      the midline chin to chest suture, but with an alkathine shell, to maintain the
      neck in flexion for ten days postoperatively. This had good results with minimal
      complications.

PMID- 23119715
TI  - The Otolaryngologist and the hearing aid.

PMID- 23119716
TI  - Effect of tonsillectomy on aso-titre.
AB  - 136 children below the age of 15 suffering from chronic tonsillitis were
      screened. 56 patients who showed a raised ASO titre above 200iu/ml were selected
      for this study. All of them underwent tonsillectomy. ASO titre estimation was
      done after 1 month;62% after 3 months;78% after 6 months and 88% after 1 year.

PMID- 23119717
TI  - Arytenoid adduction technique for correction of paralytic dysphonia.
AB  - Development of phonosurgical techniques like Medialization Laryngoplasty (M.L) or
      Thyroplasty has opened new horizons in the management of paralytic dysphonia. The
      Arytenoid Adduction (A.A) technique as originally described by Professor Isshiki
      of Japan, added a new dimension for improvement of voice in cases of paralytic
      dysphonia particularly in large posterior complimentary to medialization
      laryngoplasty over a period of 2 years are described.

PMID- 23119718
TI  - Missile injuries of face and neck : our experience.
AB  - Despite the high human and economic casts involved, conventional warfare is still
      a harsh reality. This study presents 100 cases of missile injuries of face and
      neck among service personnel involved in high intensify conflict of recent times.
      These injuries were caused by fragments of improvised explosive devices/artillery
      shells (68%), Gunshot wounds (24%) or Mine blast injury (8%). The region wise
      distribution was face (78%) and neck (22%). These injuries were classified as
      penetrating (25%) perforating (38%) and avulsive (37%).

PMID- 23119719
TI  - Functional laryngeal surgery - critical determinants of successful
      rehabilitation.
AB  - This study addresses the functional outcome and rehabilitative process in 30
      partial laryngectomies carried out for laryngeal (22) und hypoorpharyngeal (8)
      cancers at the department of H/N Surgery, The kidwai Memorial Institute of
      Oncology. Bangalore, India from 1985-1995, Special emphasis is directed towards
      post-surgical convalescence after various partial laryngeetomy techniques which
      include 6 vertical laryngectomies (V L / VPL). 17 supraglottic laryngectomies (SG
      L), and 7 supracricoid laryngectomies with Cricohyoidepexy (CHP). Rehabilitative
      success was measured with respect to the ease of dccannulation, resumption of
      normal deglutition and speech analysis - both objectively using standard speech
      analytical equipment in a speech laboratory and subjectively using the services
      of blinded judges to score recorded speech of patients. The speech analysis
      indicate that past SGL speech was the superior most followed by V L and C H P in
      that order. Aspiration was deemed as minimal and inconsequential after V L/VPL
      followed by CHP;and SGL, in the order of severity;the extended modifications to
      resect the arytenoid and / or basE of tongue and / or piriform fossa faring worse
      than classic standard technique.

PMID- 23119720
TI  - Diagnostic role of fibreoptic bronchoscopy in pulmonary tuberculosis.
AB  - Fibreoptic bronchoscopy with bronchial aspiration* washings and biopsy was
      performed in 104 patients suspected clinically and radio logically of having
      pulmonary tuberculosis diagnostic yield in 9230% (96/104) cases. Diagnostic yield
      for tuberculosis was in 69.22% (72/104)cases, it includes positive aspiration and
      washings smear in 38.46%(40/l04) patients,positive mycobacteriai culture alone in
      26.92% (28/104) casesandpositive biopsy in 3*84% (4/ 104) patients, Non
      tuberculous conditions like pneumonia and bronchogenic carcinoma were diagnosed
      in 19.23% (20/104) cases and 3.84% (4/104) cases respectively. These results
      suggest that in areas with high prevalence of tuberculosis, bronchoscopy should
      be performed for early diagnosis and initiation of therapy in sputum smear
      negative cases of pulmonary tuberculosis.

PMID- 23119721
TI  - Nasopharyngeal angiofibroma (a report of 19 cases).
AB  - Nasopharyngeal Angiofibroma is a relatively rare benign, but locally aggresive
      tumor of the nasopharynx afflicting the adolescent males. The management of these
      tumors has been a subject of much interest and controversy in the past Here we
      present a series of 19 patients of nasopharyngeal angiofibroma (with CT Scan as
      the main stay of diagnosis) managed over the last 5 years at ENT and Head & Neck
      Surgery Department of S.S.G. Hospital, Vadodara, with infraoperative internal
      maxillary artery ligation via the trans maxillary approach permitting accurate
      removal of tumor with no major post operative complications, minimal blood loss,
      good cosmetic result and no recurrence till date. If further experience with this
      approach to management in a larger series of patients has the same results,
      surgery should be the gold standard in treatment of Nasopharyngeal angiofibroma.

PMID- 23119722
TI  - Equalisation tests -applicability in otosurgery.
AB  - The high residual pressure indicated less chances of success with notable
      exceptions while lower residual pressure tended to indicate better chances of
      success in the negative as well as the positive pressure equalization tests.

PMID- 23119723
TI  - BOxing Injuries To The Nose In Nda Cadets.
AB  - Twenty two cases of Nasal bone fracture reported in 1996 and twenty cases in
      1997. of gloves, poor training, increased number of rounds and lack of rest for
      the cadets also contributed It is recommended that any nasal injury should be
      assessed by an Otolaryngologist at the earliest and remedial measures taken.

PMID- 23119724
TI  - Serum adenosine deaminase levels as an index of tumor growth in head and neck
      malignancy.
AB  - This study was conducted on 40 biopsy proved patients of head and neck
      cancers,85% of patients presented with squamous cell carcinoma in various grades
      of differentiation. When seruma denosine deaminase activity was compared between
      controls and cases, significant increase was found in the activities (control
      51.54 +/-12.09 IU/L and cases 106.87 +/-29.75 IU/ L). The duration of illness
      didn't reflect any statistical significance with the adenosine deminase activity.
      It was 97.59 +/-62.93 IU/L in case where duration of illness was 98 +/-30.98 IU/L
      in patient with more than one year of disease. The lymph node showed stronger
      correlation with adenosine deaminase activity, its level was 83.41+/-1.41 IU/L in
      patients with N(3) The rise in serum adenosine deaminase activity was found to be
      directly related to the stage I disease. It was 57.80 +/-4.60 IU/ L in patient
      with stage I disease while in patients with stage IV had 135.87 +/-18.39 IU/L of
      activity. According to histological grading, highest level was found in patients
      having squamous cell carcinoma( 113.41 +/-32 IU/L). The activity of adenosine
      deaminase decreases with radiotherapy and after surgery. This may help in
      assessing the decrease in tumour mass and improvement in patient&#x2019;s
      clinical condition.

PMID- 23119725
TI  - Incidence and types of post extubation complications following endotracheal
      intubation and tracheostomy.
AB  - This study was undertaken to study early and late post extubation complications
      following endotracheal intubation and tracheostomy. A total 60 patients who were
      admitted in Dayanand Medical College and Hospital were studied prospectively.
      They were divided into 3 groups and were screened with various modalities like
      fiberoptic laryngoscopy. Bronchoscope, X-Ray Soft Tissue Neck and CT Scan,
      Complications like glottic edema, vocal tears, vocal granuhmas and tracheal
      stenosis were seen and were accordingly managed.

PMID- 23119726
TI  - Nasopharyngeal angiofibroma: staging and management - a review of the case series
      report.
AB  - Juvenile angiofibroma is a rare, highly vascular, histologically benign but
      locally invasive tumor, affecting predominantly male adolescents. Here we present
      a case series of 45 patients of nasopharyngeal angiofibroma, their clinical
      presentation, staging and the various surgical approaches for their excision.

PMID- 23119727
TI  - Endoscopic dacryocystorhinostomy.
AB  - External OCR used to be the gold standard for the treatment of epiphora till a
      decade back. However it carried significant morbidity and the success rate was
      dismal. The advent of endoscope coupled with the understanding of anatomy of the
      lateral wall of nose opened out an avenue to deal with these cases
      endoscopically. In our series of 30 cases we achieved successful relief of
      symptoms in 28 cases after one procedure in ihe follow-up period varying from 6
      18 months. In other two cases the symptoms were relieved after the second
      procedure. The merits of the procedure are discussed in the paper.

PMID- 23119728
TI  - An autogenous foreign body in tracheobronchial tree.
AB  - Foreign body in the trachea is not uncommon but foreign body of autogeneous
      origin is rare with stray dog bite.

PMID- 23119729
TI  - The melkersson - rosenthal syndrome as a rare cause of facial nerve palsy - a
      case report.
AB  - The Melkenson Rosenthal syndrome is the rarely encountered triad of intermittent
      facial paralysis, recurrent facial oedema and lingua plicata. The intervals
      between the recurrence of symptoms may vary in duration. The cause of this
      syndrome is yet unknown. This paper discuses the pathology, clinical features and
      management as well as reports a case of this unusual disorder.

PMID- 23119730
TI  - A long standing foreign body in the ethmoid-a case report.
AB  - Headache is the most common complaint in present Jay ENT practice, it happens to
      be the most frequent and misunderstood wmptom. Foreign bodies in the paranasal
      sinuses invariably pose challenges to the surgeon due to the complex anatomy.
      Here, we present a case report of an unusual long standing foreign body of 40
      years, in the ethmoid, presenting headache as a feature, after 37 years.

PMID- 23119731
TI  - Epidermoid cyst of the submandibular gland.
AB  - Primary epidermoid cyst of the salivary gland is extremely rare and has only been
      reported once in the parotid gland A case of epidermoid cyst of the submandibular
      gland is presented, which required excisional biopsy for the diagnosis. Such
      excision is also curative.

PMID- 23119732
TI  - Isolated tracheal rhinosporidiose -a case report.
AB  - Rhinosporidiosis is a chronic fungal granulomatous disease which usually involves
      the mucous membrance of the nose and nasopharynx.We are reporting here a rare
      case of Rhinosporidiosis affecting the trachea alone without any involvement of
      mucous membrance or skin elsewhere.

PMID- 23119733
TI  - Malignant schwannoma of the lingual nerve : a case report.
AB  - Malignant schwannomas of the head and neck are rare tumours that offer various
      diagnostic and therapeutic challenges encompassing the breadth of modern
      histupatholagy, radiology and surgery, We describe the only reported case oj a de
      novo malignant schwannoma affecting the lingual nerve. Presenting a review of the
      literature and using our case for illustration we discuss some of the pertinent
      features in the management of patients with this condition.

PMID- 23119734
TI  - Malignant external otitis in an immunodeficient infant. a case report & review of
      literature.
AB  - Malignant External Otitis (MEO) usually occurring in middle aged or elderly
      diabetics is uncommonly seen in children and rarely in infants. Various studies
      done so far have proved that immunological disturbance is present in case of MEO,
      Eliashiv et al (1978) and Yust et al (1980) have proved that cell mediated
      immunity is depressed in cases of MEO occurring in diabetics. MEO occurring in a
      four month old grosslly immunadeficient infant is indeed a very rare
      presentation. Occurrence of MEO in immttuo-suppressed children, & in cases of
      AIDS, and conclusions of various immunological studies along with this
      presentaion emphasize the need of regular immuological work up in all cases of
      MEO.

PMID- 23119735
TI  - Mediastinitis following deep neck infections : A therapeutic challenge.
AB  - OBJECTIVE: To emphasize the salient features of surgical management of
      Mediastinitis occurring secondary to deep neck infections. STUDY DESIGN: Case
      series. Retrospective analysis SETTING: Institutional teaching department
      Patients Four consecutive cases of mediastinal abscess treated between 1990 to
      1996. Selection criteria were presence of deep neck infection radiological
      evidence of widening of mediastinum and confirmation of mediastinal infection at
      surgery. Computerized tomography of neck and thorax was done in one case to
      document the extent of abscess.  SARGICAL MANAGEMENT: All the patients underwent
      transcervical drainage of neck abscess and superior mediastintomy. The involved
      spaces in the neck and mediastinum were irrigated with betadine antimicrobial
      solution and negative suction drains put in the superior mediastinum ta
      facilitate contituous drainage of the mediastinum. One patient required
      intercostal chest drainage for associated empyema. Tracheotomy was done in all
      the patients. RESULTS: All the patients survived and discharged after a hospital
      stay of around three weeks. CONCLUSIONS: Mediastinal complication of deep neck
      infections can he alarmingly rapid and can be effectively managed by early
      recognition and aggressive surgical drainage combined with antibiotic therapy
      after appropriate aerobic and anaerobic cultures.

PMID- 23119736
TI  - An unusual technique for removal of occult f. b. ( glass marble ) lying in mid
      oesophagus for one year.
AB  - Foreign bodies in oesophagus are not uncommon. Due to natural anatomical
      constrictions foreign bodies get lodged invariably. Coins, bones, open safety
      pins, tumps of meat are commonly encountered in food pipe. Inhaled, swallowed or
      aspirated foreign body is a serious problem and on occasions can be fatal (
      Schloss et al 1983). Many a time these accidental inhalations or aspirations of
      foreign bodies in children is neither observed nor suspected (Cohen et al 1980),
      Cases of long term impacted foreign bodies in oesophagus are uncommon and
      particularly round glass marble for a year is rarely reported. A rare case of
      impacted marble lying in mid oesophagus for one year is reported herewith.

PMID- 23119737
TI  - Primary tubercular infection of tonsil - a case report.

PMID- 23119739
TI  - IJO & HNS - An analytical study.

PMID- 23119740
TI  - Rhinology in the new Millennium.

PMID- 23119741
TI  - Prognosticators of survival in differentiated thyroid carcinoma.
AB  - Differentiated carcinoma of the thyroid has good prognosis, even in patients
      presenting in the late stage and with distant metastasis. In India, the incidence
      of papillary carcinoma and follicular carcinoma are in the ratio of 60?40. A
      retrospective study was carried out to determine the impact of patient and tumor
      factors on survival, and to develop a simple rish group staging system to predict
      survival in patients with differentiated thyroid carcinomas. Four hundred and
      seventeen (417) patients undergoing primary treatment at our hospital between 197
      1985, were entered to the study. There were 198 follicular carcinomas and 219
      papillary carcinomas. Impact of patient and tumor variables were studied by
      drawing Kaplan Meier curves and comparing them by the Chi Sq Test. Age<=40 years
      (p=0.00001), tumor size <5cms (p=0.01), extrrathyroidal spread (p=0.001) and
      distant metastasis (p=0.00001) had significant impact on survival. These finding
      were true for a subset analysis follicular and papillary carcinomas separately. A
      Cox Regression Analysis was also performed and this showed the above factors to
      impact significantly on survival. Basing on the regression analysis we devised a
      simple risk group system and classified the patients as high and low risk. Low
      risk group patients had a significant survival advantage. Our findings show that
      the incidence of follicular carcinoma is significantly high in india (48%) and
      that 65% of our patients are in the high risk group. Incidence of contralateral
      lobe disease on completion thyroidectomy is as high as 53%. Hence, a more
      aggressive treatment policy is warranted and total thyroidectomy is the
      appropriate treatment of choice in our patients.

PMID- 23119742
TI  - Clinical profile of patients with complications following otitis media.
AB  - The paper deals with clinical profile of 56 patients with complications following
      otitis media. The clinically proved cases with complications were subjected to
      detailed radiology and bacteriology examination. The course of the disease was
      corelated with its clinical behaviour, microbial flora and treatment required.

PMID- 23119743
TI  - Effect of radiotherapy on serum mucoprotein level in carcinoma Larynx and
      Pharynx.
AB  - Serum mucoprotein level was determined in 61 individuals including 36 untreated
      patients of carcinoma Larynx & Pharynx and 25 healthy adults. Patients were
      treated by standard doses of radiation. Serum mucoprotein was again estimated
      following therapy. Patients showed a highly significant elevation in serum
      mucoprotein level as compared to controls (P<0.001). Radiotherapy caused a
      significant decline in the serum level of this biochemical (P<0.001). Stage of
      the disease had no correlation with the serum level of the mucoprotein. The dose
      of the radiation also had no relation with the decline in serum mucoprotein after
      irradiation. The fall in serum mucoprotein level was significantly higher in
      patients having complete response as compared to partial response (P<0.001),
      however there was no difference between the patients having partial response or
      no response.

PMID- 23119744
TI  - Spectrum of Head-Neck cancers at Allahabad.
AB  - A retrospective study of Head-Neck malignancy was conducted at Allahabad over a
      period of twenty two years from 1975 to 1996. During this period, 5,386 new Head
      Neck Cancer cases were reported. Peak presentation of males was in sixth decade
      and in females it was in fifth decade of life. The sex ratio in this series was
      3?6?1 while reverse sex ratio was observed in malignancies of thyroid, alveolus
      gingiva, nasal cavity and post-cricoid region. Oral cavity lesion was the
      predominant cancer followed by larynx and oropharyngeal malignancy.
      Histologically, majority (89.97%) were squamous cell carcinoma with varied
      differentiation. Factors responsible for the high incidence of Head-Neck Cancers
      are discussed. An argent need is felt for the prevention and cessation strategies
      to achieve the goal of smoke free society by the year 2000 as expressed by Dr.
      Knoop so as to revert back the present trend of preventable Head-Neck Cancers.

PMID- 23119745
TI  - Opening the stenosed nostrill: How I do it.
AB  - Acquired stenosis of the anterior nares can often be a refractory problem. A z
      plasty utilizing a cheek flap was used to obtain a one-stage opening of the
      stenosed nostril in three cases. The procedure obviates the need for prolonged
      stenting and leaves only an unobtrusive scar.

PMID- 23119746
TI  - Evaluation of vestibular functions in otosclerosis before and after small
      fenestra stapedotomy.
AB  - Vestibular functions in twenty-five patients with otosclerosis were analyzed
      before and after undergoing stapes surgery. Vertigo was present preoperatively in
      6 patients, which disappeared completely after 4-6 weeks of surgery in all the
      patients indicating the usefulness of stapedectomy. Patients with otosclerosis
      demonstrated hypoexcitability compared to controls, which was statistically
      significant for right cold and hot irrigation. Our results showed equal culoric
      abnormalities in patients with mixed hearing loss and conductive loss. Patients
      with obliterative focus at surgery had impaired vestibular functions compared to
      non-obliterative foci without any statistical significance. A longer piston used
      at surgery tends to produce more vestibular damage compared to a smaller piston.
      Finally, the degree of vestibular dysfunction seems to be inversely proportional
      to the hearing result.

PMID- 23119747
TI  - Functional anatomy of the uncinate process and its role in endoscopic sinus
      surgery.
AB  - BACKGROUND: A basic step of Functional Endoscopic sinus surgery-the most modern
      and revolutionary surgical treatment for chronic and recurring sinusitis, is
      removal of uncinate process to expose the infundibulum. The purpose of this study
      is to explore the functional role of uncinate process with special reference to
      endoscopic sinus surgery. METHODS: A fixed dose of sterile methylene blue was
      sprayed into the nasal cavities of post endoscopic sinus surgery cases, 20
      without uncinate process preservation and 20 with uncinate process preservation.
      The area of staining/deposition of the stain in the ethmoidal cavity and the
      maxillary sinuses was endoscopically observed. RESULTS: Deposition of methylene
      blue was consistently found to be occurring in a larger area of the ethmoidal
      cavity including the maxillary sinus in post endoscopic sinus surgery cases
      without uncinate process preservation. CONCLUSION: Uncinate proces probably acts
      as a protective wall by directing the allergen bearing and contuminated inspired
      air away from the sinuses and facilitating ventilation of the sinuses in the
      mucocilliary pretreated expiratory phase. Injudictious removal of the uncinate
      process especially in cases with allergic rhinosinusitis should thus expose the
      sinus mucosa to contaminated air.

PMID- 23119748
TI  - Prevalence and etiology of vertigo in adult rural population.
AB  - A survey on 10.000 adults between the age of 20 and 79 years out of a total
      population of 66.186 persons in rural settlements under the inrisduction of Union
      Territory of Chandigarh between June 1993 to June 1995 was conducted to find out
      the prevalence and various causes of vertigo. In general community, in rural
      population, we found that more people suffer from non-otologic vertigo rather
      than otologic vertigo. We found overall prevalence of vertigo in rural adult
      community to be 0.71%. Vertigo secondary to cardiovascular disease was most
      common and prevalent in 0.32% of population. Neurologic disease accounted for
      vertigo in 0.14%, metabolic disease in 0.09% and otologic disease 0.08%.
      Miscellaneous disorders were present in remaining 0.08% of population studied. To
      the best of our knowledge this study represents the first population based survey
      of prevalence of various causes of vertigo in general community in adult rural
      population.

PMID- 23119749
TI  - Snoring - A mesopharyngometric profile.

PMID- 23119750
TI  - Study of serum phosphohexose isomerase (PHI) levels in the management of head and
      neck malignancies.
AB  - The enzyme phosphohexose isomerase PHI was estimated in 43 patients of head and
      neck malignancy. The serum level of this enzyme was found to be raised in all the
      cancer patients. It was found that there were significantly higher levels of
      serum PHI in cases with metastatic lesions. The rise in PHI values was
      proportionate with the clinical stage of tumor. 29 Patients, out of 43 who had
      taken complete treatment weresubjected to post therapeutic PHI level estimations
      and the response to treatment was evaluated. Study showed that estimation of
      serum PHI levels have significant role in diagnosis of cancer, early detection of
      residual growth, recurrent growth and secondaries.

PMID- 23119751
TI  - Endoscopic transcanal myringoplasty-A study.
AB  - Aim of this study was to evaluate the role of rigid endoscope in the management
      of dry central perforation of the tympanic membrane and to compare the results of
      endoscopic myringoplasty with that of conventional myringoplasty using
      microscope. In endoscopic group there was 90% graft uptake rate as compared to
      85% in microscopic group. The results of endoscopic myringoplasty are comparable
      to the conventional myringoplasty done under operating microscope and there is no
      significant difference between the gain in A-B gap in either group.

PMID- 23119752
TI  - Endoscopic excision of Angiofibroma.
AB  - We present a case of Juvenile Nasopharyngeal Angiofibroma (JNA) managed by
      endoscopic excision alone. The selection of the case, technical difficulties and
      the advantages offered by this technique are detailed.

PMID- 23119753
TI  - Parathyroid carcinoma.

PMID- 23119754
TI  - Malignant otitis externa.
AB  - Malignant Otitis Externa, though a misnomer, definitely alarms the surgeon, the
      idea that it behaves and spreads like a malignancy, in elderly diabetics, and if
      not treated deligently, can be fatal. Though the main line of treatment is
      medical, surgical intervention should not be deferred if indicated. We are
      presenting one such case where we have not only saved the patient's life but also
      controlled the pain adequately.

PMID- 23119755
TI  - Arteriovenous hemangioma involving submandibular salivary gland.
AB  - We present a case of an arteriovenous hemangioma involving the submandibular
      salivary gland in a 20 year old girl. Hemangiomas in this region are rare. Out of
      the reported cases most have been cavernous hemangiomas. The rarity of an
      arteriovenous malformation in the submandibular salivary gland prompted us to
      report this case.

PMID- 23119756
TI  - Malignant melanoma of nose.
AB  - Malignant melanoma (MM) is one of the uncommon malignancies of the nose. We
      present an unusually big proliferative like MM in the vestibule of the nose.
      Malignancy of nose constitutes less than 1% of all malignancies (3% of head &
      neck tumour). MM however contributes only 2% of all malignant neoplasms of the
      nose (Moore & Martin. 1955).

PMID- 23119757
TI  - Solitary juvenile laryngeal papilloma.

PMID- 23119758
TI  - Haemangioma of maxillary sinus.
AB  - Though haemangioma of nose is a common tumor, those arising from the paranasal
      sinuses are not very common. Very few cases have been reported. Because of its
      rarity under the backdrop of existing literature we are reporting our present
      case.

PMID- 23119759
TI  - Tips for the novice nasal endoscopist.
AB  - Functional endoscopic sinus surgery has been a major advance in management of
      chronic sinusitis and other sinonasal diseases. However before one embarks on
      this surgery, the surgical anatomy of this region and its variations should be
      clearly understood by the surgeon, and the surgical steps of every stage of
      uperation should be mastered by adequate practice on cadavers. One has to proceed
      from simple endoscopic surgery to the advanced ones for better results.

PMID- 23119760
TI  - Management of airway problems in severely burned patients.

PMID- 23119761
TI  - Provox voice prosthesis - The Indian experience.
AB  - Following Total Laryngectomy, Tracheo-oesophageal speech prosthesis offers the
      most reliable form of voice rehabilitation. Of the various prostheses currently
      available. The Provox voice prosthesis developed by the Netherlands Cancer
      Institute has been the most popular due to its superior design and in-dwelling
      nature.At the Apollo Cancer Hospital, Hyderabad, 17 patients underwent speech
      rehabilitation with the Provox voice prosthesis between February 1999 and July
      2000. Speech rehabilitation was successful in all patients with the majority
      (82%) developing Good-Excellent speech. Two patients required replacement and one
      patient discontinued use of the prosthesis. There were no complications in any of
      the other patients.

PMID- 23119762
TI  - The role of two enzymes (LDH and PHI) and a tumour marker (CEA) in the prognostic
      evalution of head and neck malignancy.
AB  - A study of 30 patients with biopsy proven carcinoma of head and neck were taken
      and serum levels of CEA, LDH and PHI was estimated before treatment and 3 months
      post treatment. 30 patients were taken as controls for comparison. Pre- and past
      treatment levels were statistically compared and the role of surgery,
      radiotherapy and chemotherapy compared. Variation with metastasis and with
      smoking was also evaluated.

PMID- 23119763
TI  - Gujarat earthquake - Our experience of the first 7 days at referral hospital,
      Ahmedabad.

PMID- 23119764
TI  - Treatment of tinnitus: Consider psychological aspects.

PMID- 23119765
TI  - Modified epley manoeuvre -A domiciliary therapy.

PMID- 23119766
TI  - Pattern of ear, nose, pharynx, larynx and oesophagus(enplo) cancers in a rural
      based hospital.
AB  - A total of 1527 cases of total body cancer (TBC) presented at M G I M S between
      1(st) Jan. 1992 to 30(th) April 1999. ENPLO cancers comprised 656 (42.9%)casees.
      Ca cervix was the commonest cancer amongst TBC comprising 15.3% cases. Ca oral
      cavity was the commoncest among ENPLO cancers comprising 24.3% cases followed by
      Ca oesophagus comprising 19.1% Ca oropharynx comprising 16.9%, Ca hypopharynx
      comprising 13.4%, Ca larynx comprising 11.3% and Ca Nose and PNS comprising 5.7%
      cases. ENPLI cancers constiuted the major burden of TBC in our hospital.

PMID- 23119767
TI  - Rhinosporidial infection in west bengal-a calcutta based hospital study.
AB  - Rhinosporidiosis is one of the common tropical diseases in ENT practice. In the
      present study, it constitutes about 1% hospital admission for E: surgery per
      annum. Nasal and extranasal involvement particularly occular involvement was
      critically examined in this study. Complete excision of rhinosporidial mass under
      endoscopie guidance for nasal rhinosporidiosis is found to give superior result
      in term of recurrence.

PMID- 23119768
TI  - Ultrasonography of non-endocrine neck masses.
AB  - Though clinical examination is usually adequate for making a probable diagnosis
      in neck swellings, yet in a good number of situations this doesn't happen. The
      useful modality of ultrasonography was applied in thirty such cases. The use of
      this investigative techneque helped n;ot only to determine the true nature of the
      swellings and its relation to vital adjacent structures, but also aided in making
      decision regarding early surgical treatment of inflammatory swelling.

PMID- 23119769
TI  - Assessment of diagnostic parameters in meniere's disease.
AB  - Meniere's disease has been ever served as one of the most debatable issue amongst
      the otologist. Various proposals for it's accurate diagnosis have arised in
      medical forefronts. The randomized study over here, of various diagnostic
      criteria in 52 nos are critically analysed in view of confirmation of clinically
      suspected Meniere's disease.Conclusions are drawn on basis of the autcomes of
      BERA,EcochG and caloric tests in form of individual as well cobined sensitivity
      in favour to attempt to standardize the deciding parameters in relation to the
      stage of the disease.

PMID- 23119770
TI  - Peritonsillar abscess-a clinico-bacteriological study.
AB  - This study comprised 32 cases of peritonsillar obscess (PTA)constitutint 0.08% of
      ENT outdoor cases and 0.80% of indoor admission. Age ranged from 14 years to 58
      years(mean 34.21 +/- 10.25 SD years). Male predominance was seen in the ratio of
      1.69:1. A triad of symptoms comprising pain, fever and peritonillar swelling was
      seen in 29 (90.62%) cases. Ipsilateral jugulodigastric lymphnode enlargement was
      the commonest sign present in all the cases. Bacterial culture was positive in 25
      (78.12%) cases. Most common aerobic organism isolated was Group A beta hemolytic
      streptococcus (GABHS) seen on 10 (27.77%) cases. Anaerobic culture could be done
      in 22 cases only. It was positive in 11 (50%) cases. Commonest isolate was
      Peptostreptococcus seen in 4 (18.18%) cases.

PMID- 23119771
TI  - Industrial noise pollution and conservation of hearing-a study of mine workers.
AB  - Noise as such is achieving dangerously alarming proportion and proving hazardous
      in all spheres of life, and industries are not exception to it. Coal industry is
      constantly involved in nation building and the miners working near by machinery
      should be protected against ill effects of noise. An attempt is being made to
      conserve hearing without hampering the normal working in this study and
      statistically it has proved very useful.

PMID- 23119772
TI  - Anatomic variations of the bone in sinonasal C.T.
AB  - Coronal plane Computed Tomographic (C.T) Scanning of paranasal sinuses is
      importannt as a preoperative evaluation tool and providing a road map for
      Functional Endoscopic Sinus Surgrey. The present study wea crried out on 61
      patients of chronic sinusitis who underwent C.T. Scan of paranalal sinus,
      (coronal section) prior to Functional Endoscopic Sinus Surgery.The incidence of
      anatomical variations of the bone such as Agger nasi cells, Middle turbinate
      pneumatisation, Heller's Cells,Paradoxically curved middle turbinate, Deviated
      septum and Uncinate process variations, etc. were investigated in each C.T.Scan.
      Mucosal abnormalities in each paranasal sinus were also reported.The purpose of
      this investigation was to determine the background prevalence of bony anatomical
      variations and mucosal abnormalities of paranasal sinuses and assess the possile
      pathogenecity of these findings in patients undergoing evalation for Functional
      Endoscopic Sinus Surgery.

PMID- 23119773
TI  - Neurofibrosarcoma in the nasal cavity.
AB  - A nine month old male child presented with a swelling protruding from the right
      nasal cavity for two months. Other symptoms were mild breathlessness during
      suckling and blood stained nasal discharge. CT Scan sshowed a mass arising from
      the lasteral wall of the right nasal cavity with mild erosion of the adjacent
      bones. The tumor was excised with wide margin through a lateral rhinotomy
      approach under general anaesthesia. In histopathological examination it was found
      to be a low grade neurofibrosarcoma. The child recovered well and is free from
      any recurrence till the time of reporting.

PMID- 23119774
TI  - Laryngeal chondroma.
AB  - Cartilaginous tumors of laryngeal skeleton are a rarity: Laryngeal chondroma is
      an unusual cause of upper airway obstruction. The present report illustrates a
      case of a 13 year old male presenting with mass in the subglottis. Histopathology
      of the mass revealed laryngeal chondroma.

PMID- 23119775
TI  - Kikuchi's disease mimicking lymphoma.
AB  - Kikuehi's disease or histiocytic necrotizing lymphadenitis is an uncommon cause
      of cervical lymphadenopathy. Clinically it resembles tuberculosis or lymphoma.
      Although, this condition is well known to the pathologists, few ENT surgeons are
      aware of this entity.

PMID- 23119776
TI  - Middle ear malignancy masquerading as csom.
AB  - Malignant transformation in middle ear cleft is an extremely rare phenomenon,
      squamous cell carcinoma being the most likely neoplasm. Classical hallmarks of
      otologic haemorrage, facial palsy and inner ear damage may not be evident in a
      few cases though a long history of CSOM provides accolade. We present a young
      male operated upon for a seemingly benign otologic supprative illness where an
      extensively destructive malignant disease with intracranial extension was
      unveiled.

PMID- 23119777
TI  - Malignant melanoma of the nose.
AB  - Invasive tumors containing abnormal melanocvtes are termed ax malignant
      melanomas. Primary malignant melanomas of the nasal and paranasal cavities are
      extremely rare. A 65 years old female presented with bleeding from the nose and a
      gradually increasing mass in the left nostril. Histopathological examination of
      the specimen showed "poorly differentiated carcinoma" like features. But S-100
      staining proved it to be a malignant melanoma. This case is reported here for its
      rarity. The literature on malignant melanoma is reviewed and the aetiology
      pathology, diagnostic and therapeutic problems are also discussed.

PMID- 23119778
TI  - Schwannoma of the cheek.
AB  - Sehwannomas are tumors arising from nerve sheaths. In Ute Head- Neck region, they
      are commonly encountered in the parapharyngeal space. Occasionally they also
      occur in other less common sites.

PMID- 23119779
TI  - Neurofibroma of infratemporal fossa.
AB  - Neurogenic tumours form a very small percentage of all neoplastic Unions of head
      and neck region. The histological classifications of benign neurogenic tumours of
      head and neck include neurofibroma, schwannoma and neuromas. The purpose of this
      paper is to report a case of neurofibroma involving right infratemporal fossa,
      pterygopalatine fossa, nasopharynx which was treated surgically through a
      transmandibular approach.A benign tumour arising in this anatomical position
      requires a conservative surgical approach for cosmetic reasons, in this case
      access was provided by mandibular swing, after lateral mandibular osteotomy in
      front of the angle of mandible. This surgical procedure provided useful access to
      such a cryptic anatomical region whilst ensuring a satisfactory cosmetic result.

PMID- 23119780
TI  - Extranodal lymphoma.
AB  - Lymphomas in the extranodal sites are usually of Non-Hodgkin's variety Maxilla
      and mandibular involvement are usually far and few and GIT involvement with
      primary paranasal lympphomas are nearly unheard of.

PMID- 23119781
TI  - Invasive sino-nasal pseudallescheriasis in a non-immunocompromised patient.
AB  - Pseudallescheriasis is a spectrum of clinical diseases involving Pseudallescheria
      boydii, a soil and water inhabiting fungus. The organism is of low virulence, but
      is a fungal opportunist able to elicit infections similar in terms of variety and
      pre disposing factors to those of Aspergillus species(3). Involvement of the nose
      and the sinuses is very rare(7). Here we present a case of invasive
      Pseudallescheriasis involving the nose, paranasal sinuses and orbit in a non
      immunocompromised person. Surgical debridement followed by systemic antifungal
      therapy was given. The fungus resembles hyaline moulds like Aspergillus very
      closely in tissue sections and can be a diagnostic challenge to the pathologist.

PMID- 23119782
TI  - Laser in treatment of laryngeal amyloidosis: A case report.
AB  - Amyloidosis is the extracellular deposition of the fibrinous protein amyloid in
      one or more body sites. Amyloidosis may broadly be classified as either primary
      or secondary. Primary amyloidosis is idiopathic (56%), whereas the secondary form
      is associated with a chronic inflammatory or infectious process (5%), Amyloidosis
      is also related to multiple myeloma (26%). senescence (5%) and where tumor like
      deposits occur in isolated organs without systemic involvement (8%).Laryngeal
      amyloidosis is a rare discase. Surgery has been the mainstay of treatment either
      endoscopically or by an external neck approach. One case of laryngeal
      amyloidosis, treated with endolaryngeal microsurgery and carbon dioxide laser is
      presented with a follow up of 8 years.

PMID- 23119783
TI  - Haemorrhagic cystic sino-nasal fibrous dysplasia.
AB  - A 9 years old boy reported with left nasal blockage, occasional left nasal
      bleeding, protruding left eye ball and widening of the nasal bridge for the last
      nine months. Clinical examination and radiological evaluation were suggeitive of
      fibrous dysplasia. Mass was excised by transfacial and transcranial approach.
      Histopathology of the excised muns proved to be a case of haemorrhagic cystic
      sino-nasal fibrous dysplasia.

PMID- 23119784
TI  - Management of tracheocutaneous fistula.
AB  - We describe a simple technique that utilises local skin flaps of closure of a
      large tracheocutaneous-fistula with a adequate support to the tracheal wall by
      double breasting of local flaps, thus avoiding the post-operative respiratory
      problems that can occur due to a single flap projecting into the tracheal lumen
      during inspiration.This technique avoids the complications associated with
      primary closure of fistulae & also the morbidity of waiting for secondary closure
      to occur. It also precludes the need for a more extensive operation in the form
      of muscle flap rotation. The fistulous tract does not need to be excised but
      forms a component of the repair.

PMID- 23119785
TI  - Surgical treatment for chronic sinusitis - whether functional endoscopic sinus
      surgery has established itself?
AB  - Sinusitis affects millions of people each year. Recurrence of chronic sinus
      disease despite conventional medical or surgical treatment is a challenge to
      otorhinolaryngologists in the present day. The key to FESS is an understanding of
      underlying mechanisms of paranasal sinus disease. Fundamental to underlying
      pathology is the marked anatomic variation of lateral nasal wall causing
      ventilatory defects in the region of ostiomeatal complex, middle meatus and the
      anterior ethmoid. This area bears the brunt of inspiratory flow and it is here
      that particular impaction occurs..In FBSS, the primary intent is to remove
      ogstructing tissue in the region of osteomeatal complex so as to reestablish
      mucocilliary flow with natural drainage. However this is only the tip of the
      iceberg, there are many other factors to be taken care of, so that clinical
      utility of this technique comes into use where the aim is high success rate,
      maximal safety, relative ease of leamins and its feasibility.100 patients were
      taken up for study for a duration of 2 years with mean, follow up of 15 months,
      in each case, in the department of ENT, JNMCH, AMU Aligarh.

PMID- 23119786
TI  - Computers in Otorhinolaryngology : New horizons.
AB  - There has been an explosion in the computers and information technology in the
      past couple of years. Otorhinolaryngology has also seen a number of new
      applications of computers. This article aims to familiarize the reader with
      different uses of computers as applied to the field of Otorhinolaryngology. It
      deals with the role in medical literature search, patient and doctor education,
      medical record Keeping, telemedicine, internet and E-mail. creating virtual
      environments and its role in FESS, skull base tumors and plastic surgery.

PMID- 23119787
TI  - Supraoesophageal manifestations of gerd- A myth or reality?
AB  - Gastroesophageal reflux disease (GERD) is a disease that has come to limelight in
      the rreent past to account for various ear, nose and throat disorders. Fifty
      patients from my outpatient department, presenting with chronic dry paroxysmal
      cough, choking spells, globus sensation, voice change, burning throat syndrome,
      dysphagia were evaluated, with both invasive and non-invasive techniques like
      Fibreoptic Nasoendoscopy, Nuclear Scintigraphy with technetium, Barium swallow,
      sans pH monitoring which is an expensive and laborious method.We have shown
      evidence of GER with help of Nasoendoscopy, which revealed posterior laryngitis,
      erythema of arytenoids and interarytenoid oedema. This is corroborated with
      Scintigraphy done in Nuclear Medicine department, which is our gold standard for
      labelling the cases as GERD. Basing on the investigations, we have treated
      successfully fifty cases with medical treatment consisting of H2 Hockers, proton
      pump inhibitors and microlaryngeal surgery wherever necessary. In this article we
      are discussing the various symptoms, the fifty patients complained of, and how we
      are able to pinpoint the diagnosis and the modality we adopted with the
      facilities available, and also a brief review of literature.

PMID- 23119788
TI  - Para pharyngeal space tumors : An overview.
AB  - Tumors of the Parapharyngeal space are rare lesions. The present paper briefly
      discuss the pre-operative evaluation and surgical approach used in 4 patients. A
      C.T. Scan is extremely useful adjunct in pre-operative diagnosis and allowed us
      to ascertain the location, size, vascularity and relation of tumors to the
      surrounding anatomical structures with differentiation of parotid and extra
      parotid tumor. Imaging techniques established the site of origin with 96%
      accuracy (Richardo L Carrau, Myers, 1990), which is essential in planning
      surgical approach and predict prognosis.

PMID- 23119789
TI  - Juvenile nasopharyngeal angiofibromas with unique extrapharyngeal extensions.
AB  - From June 1999 to May 2000, 13 canes of Juvenile nasopharyngeal angiofibroma were
      diagnosed and treated in our department. From this series, 3 cases are
      highlighted here for their unusual extrapharyngeal presentation. Bio-mechanisms
      of these spreads are described. Management protocols are also discussed for these
      difficult cases.

PMID- 23119790
TI  - Olfaction - Quantification and management.
AB  - Patients with olfactory disorders are often referred to the otolaryngologist for
      assessment and treatment. Karely, however, is the otolaryngologist prepared to
      provide such services. In a previous paper in this journal, we described the
      basic anatomy and physiology of the olfactory system. Additionally, we listed a
      standardized nomenclature for classifying olfactory disturbances, and reviewed
      means for clinically assessing such disorders. In this paper, we provide a more
      detailed protocol for evaluating patients with loss of smell, incorporating
      sensory, imaging, and medical approaches employed at the Smell and laste Center
      of the University of Pennsylvania, USA. Examples of common syndromes encountered
      in everyday practice are deicribed.

PMID- 23119791
TI  - Complication of frontal sinusitis-Not amenable to endoscopic surgery.
AB  - Endoscopic sinus surgery has brought a change in the concept of treatment of
      sinus disease. Frontal sinusitis, however, still gives rise to intra and
      extracranial complication often musked by antibiotic intake. Where endoscopic
      surgery may fail to completely eradicate disease or even not be feasible due to
      various anatomic factors and other limitation. It is here that the tried and
      trusted external approach to the frontal sinus finds a role even today. Four such
      cases of various complication not amenable to endoscopic sinus surgery are
      presented here with the view of maintaining the necessity of keeping the external
      approach within the present day surgical palette when treating complication of
      frontal sinus disease.

PMID- 23119792
TI  - Modified portex tracheostomy tube.

PMID- 23119793
TI  - Transmandibular approach to total maxillectomy.
AB  - Total Maxillectomy through transfacial approach has been practiced in the
      treatment of Cancer for more than a decade. Its role in T(3) - T(4) tumors
      extending posteriorly through gthe bony wall is questionable, since an
      oncological radical procedure is often not possible. Recurrences in the
      infratemporal fossa are common. Despite the addition of radiotherapy five year
      survivals have not significantly improved. Transmandibular approach to Total
      Maxillectomy overcomes this shortcoming by including the pterygopalatine fossa
      enbloc with the maxilla. Early experience is presented.

PMID- 23119794
TI  - Summating potential & summating potential/action potential ratio in the diagnosis
      of Meniere's disease.
AB  - This study assesses electrocochleographic (ECOG) potentials in a clinically
      defined Meniere's group and compares the results with those from a normal control
      group. Electrocochleography was done in 42 cases of Meniere's disease and was
      compared with 20 normal cases. All parameters of electrocochleography were
      studied with special emphasis on the summating potential/action potential (SP/AP)
      ratio. A SP/AP amplitude ratio of 0.49 was found in the Meniere' group as
      compared to the SP/AP ratio of 0.03 in the control group. Latencies of SP and AP
      were also studied and compared between two groups.

PMID- 23119795
TI  - Endoscopic sinus surgery in children with chronic sinus disease failed on medical
      management.
AB  - This pilot study assessed the safety and efficacy of Endoscopic Sinus Surgery
      (ESS) in children with chronic sinus disease. A total of 150 patients were
      carefully evaluated for intractable signs and symptoms of chronic sinus disease
      and 40 children were deemed appropriate candidates for ESS. All patients were
      medical management failures. Thirty percent of these children had bronchial
      asthma and fifteen percent had allergies. All patients were followed for atleast
      one year after surgery. Overall success rate as assessed at one year was 85.3%.
      The success was evaluated by a scoring system evolved out of this study for the
      subjective relief of symptoms. The commonest surgical complication observed was
      synechiae between the middle turbinate and the lateral nasal wall, that developed
      in 10% cases. The revision surgery was required in only 5 children who had
      associated systemic illness like bronchial asthma or allergies.

PMID- 23119796
TI  - Audiovestibular changes in diabetes mellitus.

PMID- 23119797
TI  - Classical Neo-stapedotomy.
AB  - Preservation of stapedius muscle and incudo-stapedial joint during stapedotomy
      for otosclerosis is the motto of the dat. The Study was carried out in 500
      patients. In Group A (n = 140), the stapedius muscle and incudostapedial joint
      were preserved. In Group B (n = 360), the stapedius muscle was cut. One month
      after surgery in Group A patients, the Stapedius-Reflex (SR) was evoked in 75%
      and three months later in 90%. The mean Loudness Discomfort Level (LDL) after one
      month of surgery in Group A was 95dB while three months after it was increased to
      110dB. Speech discrimination score (SDS) in Group A with 80 dB suprathreshold is
      93% and in Group B it is only 72%. This study established the fact that the
      preservation of stapedial muscle and incudo stapedial join is beneficial and
      essential, whenever possible, in the surgery for otosclerosis.

PMID- 23119798
TI  - Prophylactic budesonide nasal spray after polypectomy.
AB  - This double blind study compared the effect of budesonide nasal spray with
      placebo, in the prophylaxis of nasal polyp recurrence after avulsion. 38 cases
      were given budesonide nasal spray and 25 placebo for 3 months after polypectomy.
      Follow up of 9 months revealed budesonide treated patients to have significantly
      lower recurrence rate as compared to the placebo. Interestingly patients with
      recurrent nasal polyposis benefitted much more from topical budesonide treatment
      as compared to ones with no previous history of polypectomy.

PMID- 23119799
TI  - A prospective randomised study to assess the efficacy of differenct medications
      for relief of post-operative nasal obstruction.
AB  - Surgery to the nasal septum and to the turbinates constitutes a significant part
      of the workload of an otolaryngologist. The patient invariably experiences short
      term nasal obstruction following such surgery and different medications are
      commonly used to relieve this and to promote a sense of airway patency. However
      the efficacy of topical and systemic medication, given in the post-operative
      period is hot well documented. A prospective randomized trial was therefore
      undertaken to compare the efficacy of a topically applied vasoconstrictor and an
      anticholinergic agent in reducing the sensation of airway obstruction in the
      first week following simple nasal airway surgery. 0.5% Ephedrine hydrochloride
      nasal drops, Pseudoephedrine tablets and a combination of the two were compared
      to a control group who received no treatment. Eighty patients were randomised
      into four groups and nasal patency assessed by patients using a visual analogue
      sacle (VAS). When compared to the control group both medications were effective
      in relieving nasal congestion but a combination of topical and systemic therapy,
      given together, was superior to either agent used alone. The results achieved
      were independent of the seniority of the surgeon undertaking the operation.

PMID- 23119800
TI  - Neck mestastasis from unknown origin-results of planned primary surgery and post
      operative radiation therapy.
AB  - Ninety-two patients with metastasis of unknown origin were studied between 1986
      and 1997 at Kidwai Memorial Institute of Oncology, India. Treatment included
      planned primary radical neck dissection followed by radiotherapy. Sixty-seven
      patients completed our multimodal therapy. Thirty-eight of these patients had a
      median follow-up pf 35.7 months. Nine patients had a median follow-up of 8.3
      months. Twenty patients were lost in follow-up after completing the above
      protocol. Twenty-five patients did not comply with prescribed therapy. Of the
      followed up patients 78.9% were disease free. The failure rate was 21%, which
      comprised of regional failure in 16% and liver metastasis in 5%. Primary
      manifested at base of tongue in 2 patients. In a third world cancer center like
      ours, advanced neck disease and unreliable follow-up mandate multimodal therapy
      to be instituted at the first instance. Manifest primaries should be treated on
      individual basis.

PMID- 23119801
TI  - Evaluation of tympanostomy tubes in middle ear affections.
AB  - One hundred cases of Chronic Tubotympanitis with or without effusion were treated
      by myringolomy and Grommet insertion in the tympanic membrane. 60% cases
      presented with effusion and 40% with tubal catarrh. Hearing loss of conductive
      type 15-45dB was the main feature in all the cases. The effusion (serous, mucoid
      and mixed type) was drained in 84% of the cases. The recovery in the state of
      middle ear was evident in 80% cases showing return to normal tympanogram of type
      'A' from type 'C' and type 'B' variety suggesting equalisation of middle ear
      pressure with the atmospheric pressure after the Grommet insertion. Excessive
      bleeding (12%), Permanent perforation (8%), worsening of hearing (8%) and
      extrusion of grommet (4%) were the only complication observed.

PMID- 23119802
TI  - Blast injury ear in a low intensity conflict.
AB  - The Eardrum is the most sensitive organ involved i blast injury and can be
      ruptured at relatively low pressure differentials. This study presents 200 cases
      of traumatic perforation among service personnel involved in a low intensity
      conflict, treated in a forward zonal hospital. Most blast injuries of the
      tympanic membrane (TM) heal spontaneously with conservative treatment (83%).

PMID- 23119803
TI  - Fibro-osseous lesions of the maxillo-ethmoid complex with orbital involvement.
AB  - Fibro-osseous lesions involving the maxillo-ethmoid complex are rare. Extensive
      lesions leading to proptosis are rare still. We report here 22 cases of fibro
      osseous lesions with orbital involvement. CT scan was the mainstay of
      radiological investigation. Transfacial excision was done in all cases, except
      three which necessitated a cranio-facial resection. Surgery resulted in
      significant reduction of proptosis and improved cosmesis in all cases. In three
      instances, a sliver of the tumor tissue was left behind due to its proximity to
      the dura or optic nerve. Two of these cases however went on to develop subsequent
      visual loss secondary to disease progression. Six cases necessitated revision
      surgery for residual or recurrent lesion.Disease extension to the proximity of
      vital structures should be excised as continuing tumor growth may prove unsafe.

PMID- 23119804
TI  - Carcinoma of external auditory canal.
AB  - Tumors of external auditory canal are rare and malignant neoplasms of external
      auditory canal are uncommon. We report two cases of carcinoma of external
      auditory canal. Primary carcinomas of the external auditory canal are rare, the
      incidence being approximately two cases per one million per year. Incidence in
      females is more than males (1). The cases are usually diagnosed late because of
      the absence of significant presenting complaints.

PMID- 23119805
TI  - Lipoma of the external ear with osseous metaplasia.
AB  - Lipoma with osseous metaplasia of the external ear is an uncommon and has not
      been reported so far in Medline search for 30 years. The diagnosis was confirmed
      only after excision biopsy of the lesion. We report this case for its rarity.

PMID- 23119806
TI  - Unusual foreign body (broken tracheostomy tube) in left main bronchus.
AB  - Foreign bodies in the tracheobroncial tree are commonly seen in children and less
      so in adults. All manners of materials have been described as accidentally
      entering the tracheobroncial tree. Although tracheostomy tube as a foreign body
      in tracheobroncial tree is not so common, it is still well known. They present as
      emergencies and require skillful management. Few cases of tracheotomy tube in the
      tracheobrochial tree. have been reported in the literature till date. We have
      some across such case of broken fuller's tracheostomy tube (flange) in left main
      broncus and mwe are reporting this casedue to its rarity.

PMID- 23119807
TI  - Tumefactive fibroinflammatory lesion of the neck.
AB  - Fibrosclerotic and fibroinflammatory diseases are pelicular and unusual
      conditions, which may present in any part of the body. Howeverm, in the region of
      the head and the neck they are seldom seen and hence easily misdiagnosed. To
      date, about twenty-two such cases have been reported in the head and neck region.
      Presented here is a case of tumefactive fibroinflammatory disease of the neck in
      an 85-year-old woman with a detailed account of the clinical features, cytology,
      histology and postmortem findings. Also presented is a brief overview of the
      literature pertaining of this condition.

PMID- 23119808
TI  - Haemangioma of the nasal bone.
AB  - A 16 year-old female presented for her cosmetic deformity with a slowly
      progressing swelling of insidious onset on the upper part of the bridge of the
      nose slightly towards the left side for 3 year duration. Clinical & radiological
      examination revealed an intra-osseous tumor of nasal bone. Histopathologically
      the tumor was a cavernous haemangioma of nasal bone. A follow up study upto 13
      year showed no recurrence. A detailed search of world literature is carried out
      with clinical history & history of trauma. It could that nasal bone haemangioma
      is separate disease entity. The patients usually seek advise for their cosmetic
      deformity & sometime for nasal bleeding.

PMID- 23119809
TI  - Stony whartons's duct.
AB  - Sialolithiasis is a major cause of salivary gland dysfunction. Chronic
      sialadenitis promotes stone formation. Conversely the presence of calculi causes
      chronic sialadenitis. It is clear that the genesis of calculi lies in relative
      stagnation of a calcium rich saliva. The submandibular gland is a more common
      site than the parotid, sublingual and other minor salivary glands for calculi
      formation. This case is presented here because of its unusual size of the
      wharton's duct stone for its clinical interest.

PMID- 23119810
TI  - Hyperplastic candidiasis - right-oral cavity, tonsil hypopharynx and larynx.
AB  - A twenty five year old female, presented with burning in throat, Odynophagia and
      characteristic history of falling of granules, He had a verrucous type granular
      lesion right retromolar area., tonsil & its fossa, Lingual Surface Epiglottis &
      Hypoharyngeal wall, Right Aryepiglottic fold & ventricular fold Oedmatous and
      Scattered granules on both vocal folds & right Posterolateral border of tongue.
      Candida was detected in 10% Potassium Hydroxide, gram stained smear, prepared
      from tissue scrapping. Histopathology report of excised specimen was Fungal
      Granuloma. She was immunocompetent & was otherwise normal. Disease could possibly
      be attributed to virulence attributes of Candida. This hyperplastic candidiasis
      was combinedly treated with surgical excision and oral daily 100mg, fluconazole
      for six weeks, with Elevan months of follow-up. This is indeed a very rare case &
      only very few such cases, are reported so far in literature.

PMID- 23119811
TI  - A rare case of nasal desmoid tumor.
AB  - Desmoid tumor or Aggressive Fibromatosis is rarely seen in the nasal cavity and
      are prone to recurrences. A patient with earlier history of excision was treated
      with repeat ergery employing the Weber-Ferguson incision followed by post-op
      radiotherapy.

PMID- 23119812
TI  - An Otorhinological study of patients with cleft lip and palate.
AB  - 32 patients of cleft palate with or without cleft lip were subjected to
      otorhinological study from January 1998 to September 2000, with special attention
      to the rhinological anomalies, ear pathology, any deafness, discharge or any
      other findings relevant to the middle ear. Hearing loss and ear changes were not
      seen in any patient with cleft lip alone, hence these patients were not included
      in this study. These changes were confined to the patients with cleft palate
      only, with or without cleft lip. High incidence of otological anomalies (75%) and
      rhinological anomalies (deviated nasal septum in 40.6%) were seen in patients
      with cleft palate with or without cleft lip. Hearing loss has been seen (37.5%)
      in patients with cleft palate and was purely conductive in nature.

PMID- 23119814
TI  - Our own website.

PMID- 23119813
TI  - Modification of modified young's operation in the management of primary atrophic
      rhinitis.

PMID- 23119815
TI  - Cochlear implants.

PMID- 23119816
TI  - Understanding Autoimmune Ear disease a potentially treatable cause of Deafness.

PMID- 23119817
TI  - Study of Auditory function in Rheumatoid Arthritis.
AB  - Rheumatoid Arthritis may affect the auditory function and is a subject of debate.
      The exact etiopathogenesis is not known. However there is evidence of rt of
      synovial joints of ossicles. Rheumatoid Arthritis may involve the Aoditory system
      by producing conductive hearing loss, abnormal otoadmittance and sensorineural
      hearing loss. Patients with pre-existing ear disease were not included in the
      study. In the present study, effcet of Rheumatoid Arthritis on auditory function
      is observed. The Study was carried out on 25 patients of classical or definite
      Rheumatoid Arthritis and 16 controls at M.Y. Hospital, Indore.

PMID- 23119818
TI  - Arytenoid adduction technique for correction of Paralytic Dysphonia.
AB  - Development of phonosurgical techniquec like Medialization Laryngoplasty (M. L.)
      or Thyroplasty has opened new horizon in the management of paralytic dysphonia.
      The Arytenoid Adduction (A. A.) technique as originally described by professor
      Isshiki of Japan added a new dimension for improvement of voice in cases of
      paralytic dysphonia particularly in large posterior commissure defects. 9 cases
      of primary and secondary arytenoid adduction technique done as complementary to
      medialization laryngoplasty over a period of 2 years are described.

PMID- 23119819
TI  - Gerontology in ENT (Geriatric Otolaryngology) - an over view.
AB  - Age and ageing is a biological property of all living beings. It has been
      estimated that there would be more than 120 crore people by 2020 over 65 years in
      the world out of which 90 crores alone n.ill be in the developed countries. At
      present there are than 30% people in Europe who are more than 60 Years the
      highest being in Sweden. Lin India the percentage of old people is around 10
      which is comparatively low. But the total number of such people is very
      significant due to the vast population, increasing life expectancy and better
      health care. Hence there is an increasing awareness of the multitude problems in
      the field of geriatic Otolaryngology due to various degenerative changes in the
      Head and Neck region. Not only the affection of the special sense organs of
      hearing & olfaction reduces the quality of life but also the life span is reduced
      as head & neck malignancy is very common in old age. The cosmetic problems of an
      ageing face poses a formidable challenge due to the ever increasing appetite for
      a youthful appearance in the modern soicety.

PMID- 23119820
TI  - Microlaryngoscopic study of 100 cases of Hoarseness of voice.
AB  - 100 patients with hoarseness of voice were studied with the help of
      microlaryngoscopy along with other conventional methods. The peak incidence of
      the laryngeal diseases was in the age group between 21 to 30 years (28%). The
      incidence in males (56%), was more than females (44%). Maximum incidence was
      found among house-wives (29%). 72% patients had a history of vocal abuse.
      Commonest disease was vocal nodule (30%). The ratio of unilateral and bilateral
      affection was near about 5 : 4. Hoarseness of voice due to vocal nodules,
      Reinke's oedema, vocal polyps or fibroangioma was cured in 88%-100% of the cases
      by microlaryngeal surgery.

PMID- 23119821
TI  - Cervical node metastasis in Carcinoma of Pyriform Sinus: A prospective analysis
      of prevalence and distribution.
AB  - The present study included 28 cases of carcinoma of pyriform sinus admitted in
      ENT ward of SMS Hospital in year 2000. The present work has been undertaken to
      analyse the prevalence and distribution of cervical lymph node metastases in
      cases of Pyriform sinus carcinoma, to compare the incidence and distribution of
      lymph node metastasis in medial vs lateral wall pyriform sinus carcinoma and to
      review the case of pyriform sinus carcinoma in reference to symptoms, clinical
      features and histopathological tumor staging.Most of the patients were in 6(th)
      decade of life. Sex incidence observed was male 93% and female 7% Histological
      variety was moderately differentiated squamous cell carcinoma (46.5%) which
      differs from the previous studies reporting the commonest variety to be poorly
      differentiated squamous cell carcinoma.It was observed in this series that 60%
      cases were of malignancy medial wall of pyriform fossa and 40% cases were of both
      lateral and medial wall. In contrast to previous studies which suggested that
      chances of contralateral cervical metastases was more with carcinoma involving
      medial wall of pyriform sinus, we observed equal incidence of contralateral node
      metastases in both group of pyriform sinus carcinoma case.In the present study
      75% cases presented to us with T(4) stage. Though there were 4 cases of T(1)
      tumor in present series but none were in TNM stage I or II. This indicates that
      there is essentially no difference in the risk of lymph node metastases by T
      stage.

PMID- 23119822
TI  - Tracheoesophageal Puncture - an Indian perspective.
AB  - Neoplasms of the Larynx constitute a large group of malignancies in our country.
      The advanced stages of laryngeal carcinoma require a total laryngectomy, which is
      functionally and psychologically very debilitating for the patient, as he loses
      his speech. Although many methods have been devised to overcome this handicap,
      none has been proved to be entirely satisfactory. Singer and Blom (1980)
      introduced an endoscopic technique for voice restoration using a
      tracheoesophageal puncture. A one way silicone valve was used by them and they
      claimed a very high success rate. Similar good results were reported by other
      Western and Indian surgeons. However, in our series of ten patients, the results
      were not very encouraging. Sixty percent (6/10) patients could acquire speech but
      there were significant difficulties. We do not think that this technique should
      be used indiscriminately in a laryngectomee.

PMID- 23119823
TI  - Surgical management of some unusual Parapharyngeal space Tumors.
AB  - We present out experience with the surgical management of 8 cases parapharyngeal
      tumors which were successfully operated using various approaches. Most tumors
      were quite large and presented special surgical challenges to safegaurd important
      structures and ensure complete tumors excision. Included in the series are 3 rare
      tumors, a myoepethilioma of the deep lobe of parotid, a Glomus intravagale tumor
      and a case of extra osseous Ewing's sarcoma. Depending on tumors location and
      extent, the transcervical, transparotid and midline mandibulotomy approaches were
      used and the techniques are described. All patients are currently doing well
      without any evidence of disease.

PMID- 23119824
TI  - Otitis media with effusion: An audit on the indications and outcome.
AB  - One of the reasons for the variation in the number of grommet insertions amongst
      different hospitals could be that the indications for surgery differ amongst
      them. Even ENT surgeons within the same hospital may have different criteria for
      grommet insertion.Definitive criteria for grommet insertion in children with
      Otitis media with effusion (OME) were established in 1995 at the Ipswich Hospital
      NHS Trust. A subsequent audit was performed on children with grommets inserted
      between 1995 and 1996 to assess whether the indications for surgery fell within
      the defined disappointment were analysed.the result of the audit shows that 240
      out of 245 children who grommet insertion met the preset criteria. Seventy-five
      percent of the children noticed an improvement of hearing at the 6 months review.
      The overall percentabge of children with improvement of their speech, education
      and behaviour was 41.6%, 33% and 20.4% respectively. Forty-seven percent of the
      children also noticed a reduction in the frequency of acute otitismedia. On the
      whole 78.5% of the parents were pleased with the operation at the 6 month review.
      The main reason for disappointment at 6% months was grommet extrusion or the
      grommet acting as a source of discharge.

PMID- 23119825
TI  - Predictive value of Electroglottography in voice disorders.
AB  - A prospective study of 62 consecutive cases of voice disorders in which an
      attempt has been made to define the predicictive value of electrography in voice
      disorders. The overall predictability is 69.3% with a high sensitivity for mass
      lesions and mobality disorders of vocal cord.

PMID- 23119826
TI  - Effect of hearing AIDS on psychosocial dysfunctioning.
AB  - The perception of communication abilities amongest adolescents with moderate and
      profound hearing loss was correlated with indices of psychosocial adjustment.
      This was done to determine whether the use of hearing aids could play a role in
      presence and improvement of psychosocial functioning among acquired hearing loss
      persons after the use of hearing aids. Amongest the deaf population, it was found
      that hearing loss did affect the social, the vocational, the personal and
      subjective well being, after intervention. The control group did not show any
      corresponding change except that the state anxiety among this group had
      increased.

PMID- 23119827
TI  - Invasive Sino Nasal Aspergillosis diagnostic criteria.
AB  - This study highlights the high incidence of fungal granulomas in our patients and
      to streess the need to differentiate the invasive Sinonasal aspergillosis from
      the non invasive ones because, the management og invasive Aspergillosis includes
      the administration of the potentially toxic drug, Amphotericin. The various
      diagnostic criteria used by us to identify the cases for systemic anti fungal
      treatment in addition to through local debridement are discussed.

PMID- 23119828
TI  - Giant cell tumor of hard palate.
AB  - The giant cell tumors usually present in epiphysis of long bones. These are
      uncommon tumors in head and neck region. These tumors have benign historical
      features but can be aggressive locally and even can metastasise to lungs. This
      rare tumor in hard palate is being reported here which was excised transpalatly.

PMID- 23119829
TI  - Neurilemmoma of the Facial Nerve presenting as a Parotid Mass.
AB  - A facial nerve neurilemmoma manifesting as a parotide mass is a occurrence.
      Symptoms are slowly progressive and diagnosis is often delayed. We present a case
      report of a facial neurilemmoma, which presented as a parotid mass.

PMID- 23119830
TI  - Paraganglioma of external auditory canal.
AB  - In the ear, paragangliomas are commonly found in the tympanic cavity or in juglar
      bulb. We, here, present a case of paraganglioma originating from the external
      auditory canal as it has not been reported in the world literature. The clinico
      pathologic features of such a case has been described.

PMID- 23119831
TI  - A transpalatal approach (Palate Split) to the Parapharyngeal space.
AB  - This is a case of a 20 years young boy with a large parapharyngeal pleomorphic
      adenoma excised via transpalatal approach. The incision was taken about 0.5cm
      away from the edges of the tumor it provided good, surgical access to the whole
      length of upper parapharyngeal space and allowed complete tumor excision.

PMID- 23119832
TI  - Castleman's disease: Report of 4 cases of cervical Lymphadenopathy and review.
AB  - Castleman's disease is one of the rare causes of cervical lymphadenopathy. A
      study of 4 cases along with literature review has been done.

PMID- 23119833
TI  - Temporal bone Manifestations of Eosinophilic Granuloma.
AB  - Eosinophilic granuloma is one of the triad of conditions collectively known as
      Histiocytosis-X. It is an uncommon granulomatous diseas which can affect the
      temporal bone(1) Allthough initially quiescent the disease may erode the mastoid
      cortex, destroy tegmen and extend into the cranial as well as erode the
      semicircular canals, cochlea or facial canal, giving rise to facial palsy. These
      lesions almost always become infected and can confused with chronic
      otomastoiditis. When diagnosed, theraphy consists of conservative surgery,
      radiation theraphy, steroids and chemotherapy(2).

PMID- 23119834
TI  - A rare case of Hamartoma of nose and upper lip.
AB  - Hamartoma though quite common in face and head-neck region, huge size of such a
      magnitude is not very common- hence the case is being reported.

PMID- 23119835
TI  - Inhaled foreign bodies in laryngectomees.
AB  - As a consequences of laryngectomy, patients possess a tracheostoma presenting on
      the neck skin which is an intrinsic component of their airway and which provides
      a portal through which potentially dangerous foreign bodies can enter the
      tracheobronchial tree. In addition, new methods of speech rehabilitation require
      the placement of a valve within the stoma which needs regular cleaning and
      manipulation. We report 3 cases of aspiration, each of a different piece of
      equipment that is commonly associated with laryngectomees, illustrating potential
      unique risks to the airway in such individuals.

PMID- 23119836
TI  - A rare case of primary extracranial meningioma of the Paranasal Sinuses.
AB  - A rare case of Extracranial Meningioma with Paranasal Sinus involvement has been
      reported with review of available literature.

PMID- 23119837
TI  - Laryngeal Tuberculosis in MDR-TB presenting as Laryngeal Carcinoma.

PMID- 23119838
TI  - An unusual complication of Thyroid Surgery and its management.
AB  - Stricture oesophagus is an unusal complication of thyroid surgery. There is only
      one case of such nature recorded in literature, which shows that the surgeon who
      operated may not have had any previous experience of head and neck surgery.
      Locating the stricture was difficult, more so planning the treatment modality was
      problematic. Informed consent for oesophagectomy with gastric pull through was
      taken. However when we explored the neck the stricture was seen just below the
      level of pyriform sinus. It could be successfully excised without end to end
      anastomosis.

PMID- 23119839
TI  - Congenital anomalies in e.N.T.

PMID- 23119840
TI  - The 53rd year of IJO & HNS an appraisal.

PMID- 23119841
TI  - A need to strengthen our resident training programme in E.N.T.

PMID- 23119842
TI  - Antrochoanal polyps and allergy-A comparative study.
AB  - Antrochoanal polyps, are solitary polyps arising from the maxillary autrum. Their
      aetiology largely remains unknown; allergy has been implicated. The study
      attempts to define the relation between antrochoanal polyps and allergy and the
      need for such an investigation by studying 24 cases with antrochoanal polyps and
      comparing them with 20 cases of sinonasal polyps. Nasal smear cytology, serum
      total IgE and polyp fluid IgE was evaluated. 52.38% of cases turned out to be
      allergic. In their presentation, antrochoanal polyps do not significantly differ
      from other polyps.

PMID- 23119843
TI  - Butterfly inlay tympanoplasty: A study in Indian scenario.
AB  - Popularly myringoplasty is done by an underlay or an onlay technique using mostly
      temporalis fascia graft. A new technique of inlay tympanoplasty using composite
      cartilage perichondrium graft is applied in the present study of 20 patients, for
      closure of small to medium sized perforations. The results have been analysed in
      terms of graft take up rate and hearing improvement.

PMID- 23119844
TI  - Clinical profile of hoarseness of voice.
AB  - A study comprising of 110 cases of hoarseness was carried out in the department
      of otolaryngology-HNS, M.G.I.M.S., Sewagram between Jan. 1998 and Sept. 1999. Age
      of patients ranged between 6 to 71 years. Male to female ratio was 2?1. Labourers
      constituted the single largest group of patients (36.36%). Rural to urban ratio
      was 3?1. Duration of hoarseness ranged from 1 day to 5 years. Acute laryngitis
      was the commonest cause of hoarseness.

PMID- 23119845
TI  - Nasal mucosa changes in students exposed to formaldehyde vapour.
AB  - Formaldehyde has been used since ages in the various laboratories. Recently,
      interest has developed in the possible role of formaldehyde in the development of
      Squamous Cell Carcinoma. In this study 53 students (undergraduates and
      postgraduates) were exposed to formaldehyde and they were compared with 25
      students (control group) unexposed to formaldehyde. Results have shown that
      students who were exposed to formaldehyde for a longer time showed mucosal
      changes as compared to the control group.

PMID- 23119846
TI  - Endoscopic septoturbinoplasty: Our update series.
AB  - Decades have passed since septoplasty was first introduced for the management of
      the nasal airway. Various modifications of the technique have been made to deal
      with the pathology of the nasal septum. The authors have used the nasal endoscope
      successfully for the ultraconservative management of the deviated nasal septum
      and turbinoplasty [inferolateral partial resection of the turbinate/s]. The
      present study is an update series of the previously published preliminary series,
      and comprises of 480 cases of deviated nasal septum who underwent endoscope aided
      septo-turbinoplasty [EAS] to improve the nasal airway. The subjective assessment
      of the efficacy of this procedure was done by visual analogue scoring system and
      the objective assessment was done by endoscopy. This study demonstrates
      significant improvement in relieving nasal obstruction and the contact areas. The
      authors advocate a combined approach-an endoscopic approach for inaccessible
      posterior deviation and a conservative traditional technique for accessible
      anterior segment [caudal septum].

PMID- 23119847
TI  - Trouble shooting with the Tracheo Esophageal Prosthesis.
AB  - Vocal rehabilitation of the laryngectomee can be dramatically improved by the
      Tracheo-Esophageal Puncture (TEP) technique. The greatest impediment to its
      increased use in our country has been the failure on the part of the Medical
      Community to provide these patients with day to day support and guidance on the
      use of the TEP prosthesis. This article seeks to address this deficiency and
      provides some guidance on the care and maintenance of the TEP.

PMID- 23119848
TI  - Foreign bodies in the tracheobronchial tree: A prospective study of fifty cases.
AB  - Aspirated foreign bodies continue to present challenges to the
      otorhinolaryngologists-the major issues being accurate diagnosis and speedy and
      safe removal of the foreign bodies. Tracheobronchial foreign bodies are most
      common in the 1-3 year age group and are usually of vegetative origin. The most
      common signs and symptoms of tracheobronchial foreign bodies are cough, wheeze
      and decreased air entry on the affected side. Diagnostic bronchoscopy is
      recommended in all children presenting with a history of sudden onset of cough,
      choking spell, an unexplained acute wheeze, or a chronic pulmonary infection. The
      present study was undertaken to study the varied clinical presentations of
      tracheobronchial foreign bodies.

PMID- 23119849
TI  - Ligation vs. bipolar diathermy for haemostasis in tonsillectomy-a comparative
      study.
AB  - The use of diathermy for haemostasis in Tonsillectomy remains controversial. A
      thorough scan of English literature comparing the ligation with diathermy has
      been presented. The reasoning of using Bipolar instead of Unipolar is explained.
      A prospective randomized study of 376 tonsillectomy is being presented. This is
      the first study in India where Bipolar instead of Unipolar diathermy is being
      used.No significant difference was found in P.O. Hg. rates when either diathermy
      or ligatures were used. Diathermy is significantly faster method of securing
      haemostasis resulting in shorter operative a & anesthetic time, thus saving on
      cost.Long term follow-up has shown better results with diathermy & is associated
      with less pharyngitis, hyper-trophied nodes & resulis in more smooth tonsillar
      fossae.

PMID- 23119850
TI  - Effective rehabilitation after partial glossectomy.
AB  - OBJECTIVE: The surgical treatment of cancer of tongue results in speech deficits.
      Speech disorders in the glossectomised patients fall into, categories of impaired
      articulation, reduced speech intelligibility, altered oral & nasal resonance,
      impaired voice quality & reductions in global speech proficiency. Since speech is
      a social tool, its most significant measurements start with the degree to which
      it can be understood. METHODS: This study was conducted at Tata Memorial
      Hospital, Mumbai, India, An incidental sample of 25 patients was selected for
      this study. Different questionnaires specially devised for this study were used
      to assess patients' speech & deglutition post-operatively. The data was collected
      3 months after surgery of these patients. RESULTS: Studies have indicated that
      larger the segment of the tongue, the greater is the distortion of speech &
      difficulty in deglutition. All functions associated with the interaction of the
      tongue with the related anatomy of the head & neck were severely impaired
      following glossectomy. The rehabilitation plan for partial glossectomy patients
      depended upon the assessment of their post-operative articulation level,
      education, job, age, family & motivation.

PMID- 23119851
TI  - Dentigerous cyst in a young boy.
AB  - A huge maxillary dentigerous cyst in a young boy is a rare entiry as this cyst
      commonly accurs in the mundible of middle-aged persons.Massive sive as well as
      gross disfigurment reflect long-drawn neglect by the patient & his attendents,
      which seems to be a rare happening in today's society.Though, in zhildren the
      present trend of management is marsupiadisation of dentigerous cyst to make
      unerupted tooth erupf, but as in this case, huge entargsment had made the
      viability of displaced tooth qmertinmable, its removal was rought for Moreover,
      as the cyst had lined the amtral cavity, here, marsupialization would have led to
      an oroaniral firtula with antral simusitis, which was arerted by enucleation of
      the cyst through Caldwall-Lac approach.

PMID- 23119852
TI  - A bullet in the parapharyngeal space.

PMID- 23119853
TI  - Klippel-trenaunay weber syndrome.
AB  - A 36 yrs old male patient presented with a 4 months history of a mass in neck
      along with a small swelling on the forearm from past several years. There was
      neither any bony involvement nor mental abnormality. He was operated upon and
      followed up for 2 years when ultimately he was cured. The case is reported due to
      its rarity and unusual presentation.

PMID- 23119854
TI  - Spontaneous CSF otorrhoea - Presenting as conductive deafness.
AB  - Spontaneous CSF otorrhea specially in older age is a rare condition. Congenital
      inner ear malformation is one of the commonest causes in pediatric age group and
      either because of trauma or spontaneously it comes out into middle ear. In
      pediatric age group usual presentation is with history of meningitis while adult
      patients may present as watery discharge from nose or ear. This is a case,
      presented with conducted deafness with negative middle ear pressure. Grommet was
      put presuming secretory otitis media but B2-transferrin levels of the secretion
      confirmed it as a CSF otorrhea. He was operated with past aural transmasioid
      approach. The defect was sealed in layers. Patient is in regular follow up is
      asymptomatic and without any recurrence.

PMID- 23119855
TI  - Primary tumor of the facial nerve: Diagnosis and management.
AB  - Benign primary tumors of facial nerve are rare, difficult to diagnose due to
      their subtle and variable clinical manifestations and these are usually
      misdiagnosed as idiopathic facial nerve paralysis. A case of facial nerve
      sehwannoma in internal auditory meatus presenting as a tumor indistinguishable
      from acoustic neuroma clinically is presented here. Difficalties in patient
      assessment, inadequacy of diagnostic techniques presently available and surgical
      technique of the removal of the tumor will be discussed.

PMID- 23119856
TI  - Cystic acoustic neuromas.
AB  - Predominantly cystic acoustic neuromas are rare and they usually present with
      clinical and radiological features different from their more common solid
      counterparts. Two cases of cystic acoustic neuromas are reported here.

PMID- 23119857
TI  - Stitchless Tonsillo-styloidectomy.
AB  - In a retrospective study carried out at Nangia ENT Hospital Gurgaon, 210 operated
      cases on Tonsillectomy. Adenotonsillectomy and Tonsillo-styloidectomy for period
      of 4 years and 3 months w.e.f. Janurary 96 to April 2000 were analysed.

PMID- 23119858
TI  - Adenoid cystic carcinoma - Clinical presentation and cytological diagnosis.
AB  - Adenoid cystic carcinoma is a tumor arising from the minor salivary glands, the
      palate being the commonest site. It accounts for about 1% of all head and neck
      malignancies. We report a case with the typical presentation of a palatal growth
      with extensive intra-cranial invasion. The diagnosis of this case and a brief
      review of literature is discussed. Final diagnosis of this case was made from
      cytological reports. The dry smears stained with MGG were found to be definitely
      superior to the alcohol fixed slides stained with papanicolaou. The aim here is
      to highlight the importance of cytology in the diagnosis of such tumors.

PMID- 23119859
TI  - Tonsillar carcinoma: A review.

PMID- 23119860
TI  - CCG & ENG as diagnostic tools in lesions of central vestibular disorders.
AB  - The article presents the author's experience with CCG & ENG in diagnosis brain
      stem & cerebellar tumors over a period of one year.

PMID- 23119861
TI  - Cochlear implant electrode insertion: Jacobson's nerve, a useful anatomical
      landmark.
AB  - The classical technique in approaching the scala tympani through the round window
      niche by way of facial recess has not always been successful. There have been
      recent reports on false insertion of the electrode array into the hypotympanic
      cells tracts or infralabrynithine cells tracts. In these cases the round window
      niche are situated posterior, or obliterated due to bony growth, or sclerosed at
      the basal turn of the cochlea. Therefore, successful intubation of the scala
      tympani much depends upon the position of the round window niche and patency of
      the basal turn of the cochlea. The present study was conducted in an attempt to
      elucidate factors that determine the ease of insertion of an electrode array, and
      to by-pass the initial turn of the basal cochlea (hook area). The jacobson's
      nerve (JN) landmark was used to perform cochleostomy by drilling anteriorly or
      through the nerve. The inferior segment position of the basal turn of the cochlea
      studied in relation to the JN and successful intubation of the scala tympani was
      achieved. Also, critical anatomical measurements were made pertaining to this
      surgical technique.

PMID- 23119862
TI  - Tonsillectomy using harmonic scalpel.
AB  - Surgery of tonsils are associated with risk of haemorrhage and post operative
      pain. Harmonic scalpel is a new device which we have been using to perform
      tonsillectomy for the last one year. This instrument reduces dissection time,
      intra-operative bleeding and post operative pain.

PMID- 23119864
TI  - Children of a lesser god-the otolaryngologists.

PMID- 23119865
TI  - Clinical utility of diustortion product otoacoustic emissions.

PMID- 23119866
TI  - Study of bacterial flora in csom and its clinical significance.
AB  - Middle ear infection of varying degree is one of the common condition in general
      practice, particularly in our country. Its importance lies in its chronicity and
      its dreaded complications. Chronic suppurative Otitis media (CSOM) and its
      complications are among the most common conditions seen by the otologist,
      pediatrician and the general practitioner. Both gram positive and negative
      organisms are responsible for infection of the middle ear.The study was primarily
      carried out in 100 cases of C.S.O.M. to determine the bacterial flora and to
      study the antibiotic sensitivity pattern of the organisms isolated. The frequent
      presence of C.S.O.M. and its poor response to the routine treatment were the
      factors which were responsible for undertaking this study.

PMID- 23119867
TI  - A comparative study of fine needle aspiration cytology, ultrasonography and
      radionuclide scan in the management of solitary thyroid nodule : A prospective
      analysis of fifty cases.
AB  - Solitary thyroid nodule is a common clinical entity encountered by the
      otorhinolaryngologist and physcians. The optimum diagnostic strategy for the
      euthyroid patient with a soilitary thyroid nodule is still a matter of debate.
      The goal of diagnostic workup now is to select those patients for surgery who
      have a high likelihood of harbouring malignancy in the solitary thyroid nodule.
      The present study was undertaken to evaluate the utility of FANC in the
      preoperative diagnosis of solitary thyroid nodule and to evaluate the efficacy of
      FNAC, VSG and RNS in differentiating between benign and malignant nodules. It was
      found that FNAC is a safe, reliable and cost effective diagnostic modality with a
      high sensitivity of 83.3% and specificity of 100% and is the single best
      investigation for preoperative evaluation of solitary thyroid nodules to
      differentiate between benign and malignant nodules.

PMID- 23119868
TI  - A study on peripheral vertigo in a Kolkata based hospital.
AB  - A dizzy patient always remains a challenge to an E.N.T. surgeon. History is the
      key role and may be the only positive clue. An overall neurological assesment
      with special emphasis on nystagmus should be given. A comprehensive workout has
      been attempted in this study of vestibular disorders.

PMID- 23119869
TI  - Cytology in the otorhinolaryngologist's domain - a study of 150 cases,
      emphasizing diagnostic utility and pitfalls.
AB  - 150 patients with mass lesions in the head and neck area, excluding the CNS and
      thyroid gland were subjected to FNA cytodiagnosis. II out of 150 smears were
      considered unsatisfactory for diagnostic evaluation. Out of the 139 patients who
      yielded satisfactory smears, cytodiagnosis led to the following broad categories 
      inflammatory and non- neoplastic (24/139, 17.3%), benign neoplasm (60/139,
      43.2%), suspicious for malignancy (14/139. 10%) and malignant neoplasms (41/139,
      29.5%). Histopathologic follow- up was available in 120 cases. 15/24 with
      inflammatory lesions were not subjected to biopsy, rest 4 were lost to follow up
      (I had a suspicious smear and 3 the diagnosis of benign neoplasm). Correlation of
      cytodiagnoses with histopathology yielded the following results - 52 out of 57
      patients with the cytodiagnosis of benign neoplasm and having, histologic follow
      up had concordance, while 39 out of 41 cytologic diagnoses of malignancy,
      correlated with histopathology.Out of surgically sampled 9 patients, with
      inflammatory smears, 8 were benign and 1 malignant. In the suspicious category 2
      out of 13 surgically sampled patients had malignancy. Thus, excluding the
      suspicious smears the accuracy of diagnosis by FNAC in this study came to 93% and
      a sensitivity for cancer detection of 95%. We encountered a false negative rate
      of 9.0% and a false positive rate of 4.9%.The results are discussed, especially
      in the light of the misdiagnoses and ways at avoiding diagnostic : error.

PMID- 23119870
TI  - Radiotherapeutic effect on oropharyngeal flora in head and neck cancer.
AB  - The effect of radiotherapy on oropharyngeal bacterial and mycotic flora was
      studied. Thirty five patients were included from whom swabs were taken before and
      at the end of irradiation. Fifteen controls were included.It was found that
      Streptococcus pneumoniae was significantly decreased at end of irradiation, while
      there wan an increase in Staphylococcus aureus. Pseudomonas, Bacteroides and
      Candida species. There was no change in culture and sensitivity pattern prior to
      and after radiotherapy.

PMID- 23119871
TI  - Orbital and paraorbital tumors-clinicopathological profile and surgical
      management.
AB  - A total number of 31 cases of proptosis caused by primary orbital tumors,
      paranasal tumor extensions and nasapharyngeal tumors werte analysed in a
      retrospective study in relation to their age, sex, clinical and histological
      profile. Surgical management of this group of tumors depends on the anatomical
      location of the tumor and CT scan was considered as the primary modality of
      investigation. Different modalities of surgical treatment like lateral
      orbitotomy, medial orbitotomy, lateral rhinotomy, etc., have been adopted
      according to location of tumor. Surgical approaches and histopathological profile
      of the lesions causing proptosis are discussed in details.

PMID- 23119872
TI  - Unusual foreign bodies of the aerodigestive tract.
AB  - Foreign bodies in the aerodigestive tract are familiar ototaryngological
      emergencies. The diagnosis and the management in most cases is based an clinico-
      radioloigical findings. Three cases of foreign body in the nerodigestive tract
      with unusual presentation are being described here.

PMID- 23119873
TI  - Management of tracheo bronchial foreign bodies-a retrospective analysis.
AB  - This paper deals with 50 cases of inhaled Foreign Bodies (FB) in different age
      groups over a period of 3 years. The way the cases presented, diagnostic methods
      & procedures for removal of the Foreign Bodies hare been discussed. Our series
      has been compared with other similar studies previously reported. The major
      conclusions of the study are that, Bronchascopy has in be done even when there is
      a mere suspicion of FB; Sander 's Technique of Jet Ventilation anaesthesia is a
      reliable and safe procedure; One should not hesitate to do elective tracheotomy
      if situation warrants it; A close association between anaesthetist, endocopist
      and assistants is necessary for safe Bronchoscopy; Conventional Bronchoscopy is
      an economic procedure practical in a semiurban set up in a developing country.

PMID- 23119874
TI  - Malignant otitis external-our experience.
AB  - Malignant external otitis is an extremly morbid ostomnyelits of external auditary
      canal, mastoid and skitil base caused by pseudomonas arergenosa. We report our
      experience with six cases, which we came across in ten years.Patitents' profile
      our management and results are presented. A need for increasing awareness tif the
      condition and the probability uj early diagnosis with a high index of suspicion
      in the early stages is discussed. Attempt also is done to review a few recent
      articles with special emphasis on imaging techniques and radioistope scans.

PMID- 23119875
TI  - Post-tonsillectomy pain: Different modes of pain relief.
AB  - Sixty patients aged 15 to 40 years of either sex, American Society of
      Anaesthesiologists (ASA) grade I and II, undergoing tonsillectomy, were randomly
      allocated to receive either preroperative intramuscular diclofenac sodium(group
      A) or pre- incisional bilateral infiltration of bupivacaine in the peritonsillar
      fossa (group B) or post operative Trunscutaneous Electric Nerve Stimulation -
      TENS (group C) at fixed time intervals. Pain scores (Visual analogue scale VAS, 0
      100 mm) were assessed at rest and on deglutition at 1,3,6,9,12 and 24 hours
      after surgery. Pentazocine 1actale 15 mg IV was given as rescue analgesic
      whenever VAS estimation was more than 30 mm at rest (not deglutition). Constant
      incisional pain was significantly less ( p < 0.01 ANOVA) in group C after 3 hours
      of surgery as compared to group A and B. Similarly pain on deglutition was
      significantly less (p <0.01, ANOVA) in group C during the entire study period as
      compared to Group A and B. There was significant reduction of VAS (p< 0.01)
      immediately after TENS therapy at 0, 4 and 8 hours. Rescue analgesic consumption
      was significantly lower in TENS group. Thus, TENS seems to be an effective
      therapeutic modality for post tonsillectomy pain relief as compared to the other
      two methods.

PMID- 23119876
TI  - Fibrous dysplasia of ethmoid - a rare presentation.
AB  - Monostatic fibrous dysplasia involving th ethmoid is one of the rarest lesions.
      The clinico-pathologhical featutres and management are described.

PMID- 23119877
TI  - Necrotising fasciitis of the neck.
AB  - Necrotising fasciitis is a fulminant soft tissue infection that causes necrosis
      of fascia and subcutaneous tissue while sparing skin and muscle initially. It is
      most commonly seen in adults involving the perineum, extremities and and minal
      wall. Immunncompromised patients are at an increased risk of developing this
      infection. These infections require early diagnosis, aggressive surgical
      debridaient and appropriate antibiotic therapy. Mortality rates have been
      reported to be as high as 52 and 73% in general surgery literature.(Freuschtag et
      al, 1985., Rouse et at 1982).Necrotising fasciitis of the head and neck is rare.
      The commonest cause is secondary to denial infections. We report a case of
      necrotising fasciitis of the neck secondary to a peritonsillar abscess in a
      previously healthy individual. The pathogenesis and treatment of this fulminant
      infection are also discussed.

PMID- 23119878
TI  - A case of a destructive lesion of sphenoidal sinus.
AB  - This interesting case deals with the possible origin of pituitary tumor from cell
      rests located outside the pituitary gland. In the present case we found an
      elderly lady presenting with a suspected mass lesion of the sphenoidal sinus,
      clinically suspected to be either an infective granuloma or a chordoma which
      finally turned out to be an adenoma of the pituitary gland.

PMID- 23119879
TI  - Papillary thyroid carcinoma in a 4-year-old boy.
AB  - We present a case of Papillary Thyroid Carcinoma (PTC) in a 4- year- old boy. The
      very young age of the patient and unusual presentation with respiratory distress
      prompted us to report this case.

PMID- 23119880
TI  - Ameloblastic fibro-odontoma of the maxilla.
AB  - A rare case of Ameloblastic Fibro- Odontoma in a one year old child involving the
      maxilla is being reported. The tumor appeared to be of hamartotmatous origin
      rather than neoplastic osontogertic lesion.

PMID- 23119881
TI  - An unusual impacted foreign body in the nasopharynx.
AB  - Foreign bodies are comonly seen in upper acrodigestive tract but these are lodge
      very infrequently in masopharywr.various types of foreign bodies like leech
      whitsle wood piece marble coin etc. have beenremoved from the masopharywr.It is
      unusual for a foreign body to get impacted in adcnoid tissue of the masopharywr.
      This article highlights one such rare incidence where a button was impacted in
      the adenoid mass, which could be retrived only after adenoidectomy.

PMID- 23119882
TI  - Posterior oro-pharyngeal wall tuberculosis.
AB  - Secondary tuberculosis of pharynx is quite a rare condition as pharynx is not a
      common site for clinically manifest tuberculosis. This study reports a rare and
      unusual case of secondary oropharyngeal tuberculosis in a 40 years mole patient,
      who presented with an ulceroprotiferative lesion of Oropharynx extending to
      nasopharynx and laryngopharynx which besides being tender, bled on touch. There
      was no associated cervical lymphadenopathy. Routine laboratory investigations
      were within normal range except raised ESR. Chest x- ray revealed bilateral
      apical lesions. The patient vas put on antitubercular therapy, with which the
      patient improved.

PMID- 23119883
TI  - Multiple live leeches from nose in a single patient- a rare entity.
AB  - Foreign bodies are a common cause of unilateral epistaxis in children. Both
      animate: and inanimate foreign bodies are commonly found but, leech as a cause of
      epistaxis is rare. Cases of leech infestation have been reported in the past but
      infrequently. Here we report an unusual case of bilateral epistaxis in a four
      years old child who had infestation with multiple live leeches.

PMID- 23119884
TI  - Olfication - a clinical approach.
AB  - Olfactory dysfunction usually occurs secondary to ENT causes, and most patients
      with olfactory problems prefer to consult an otolaryngologist. 1a some cases the
      ENT surgeon is required to inculcate a systematic approach while dealing with
      such patients in order to screen the possibility of other causes (apart from
      ENT). He may in turn either collaborate with another specialist (neurologist,
      ophthalmologist, neurosurgeon) for proper diagnostic work- up or otherwise
      counsel the patient in case of a benign prognosis. Thus a basic knowledge about
      the applied pathophysiology of olfaction for its proper clinical approach is a
      must for every practicing ENT surgeon. We present the gist of the experience with
      olfaction at the Smell and Taste Center of the University of Pennsylvania USA
      that is relevant to the practicing otolaryngotogist. We present the information
      in two complementary parts: a clinical approach and its quantification and
      management which will be published in a subsequent issue of this journal.

PMID- 23119885
TI  - Duplex colour Doppler sonography - role in neck metastasis.
AB  - The present study was done to evaluate the rote of Duplex colour Doppler
      Sonography in neck metastasis. 30 patients with primary head and neck cancer were
      evaluated by Duplex colour Doppier sonography and results analysed. In more than
      95% of cases, the vascular status could be established before any form of therapy
      was instituted. Compression and infiltration of carotids and internal jugular
      vein (IJV) could be demonstrated and a structured and dynamic relationship of
      metastatic nodes to the vessel wall was established.Doppier ultrasonography was
      found to be of high value in evaluating medium and large sized neck vessels but
      was of limited utility in the analysis of ncovascularisatlon within a metastatic
      node. This provided an operating roadmap for planning treatment. It is suggested
      that Colour Doppier Sonographic evaluation should be made a standard protocol in
      assessment of metastatic neck disease before instituting any form of therapy.

PMID- 23119886
TI  - Horizontal canal paroxysmal positional vertigo (HCPPV) vs classical BPPV (new
      concepts about mechanism and domiciliary repositioning of particles).
AB  - Some new modificutiont of existing diagnostic and therapeutic manoeuvres
      (repositioning of particles) have been proposed, basing an the applications of
      the principles of hydrodynamics, inertial and gravitational forces in the
      semicircular canals. The above has been tried successfully on patients with
      benign paroxysmal positional vertigo (BPPV) and horizontal eanal paroxysmal
      positional vertigo (HCPPV) which can be executed by the patients themselves at
      home without the kelp of a therapist.Benign paroxysmal positional vertigo (BPPV)
      is a well-established entity whereas Horizontal Canal Paroxysmal Positional
      Vertigo (HCPPV) is a recently proposed one. In positional vertigo any canal may
      be involved. It is quite possible that in the past this diagnosis (HCPPV) was
      missed in many of the cases of positional vertigo. Kapfschuttel nystagmus (head
      shaking nystanmas) is induced by side to side (to and fro) movements of the head
      around a vertical axis in the plane of the horizontal semicircular canal which is
      thought to be sensitise the labyrinth, Any manoeuvres that in induce nystagmus
      with or without vertino is hound to he a manifestation of an organic lesion and
      not a non-organic one. In a number of instances the postionul test Jor BPPV may
      yield negative results; but doing this test after kopfschuttel test a dormant
      positional nystagmus may appear on the surface i.e. uncovered in a number of
      cases which may have remained undetected if Kopfschutlel manoeuvre were not done.
      This implies- that by Kopfsi huttel test both the horizontal and vertical canals
      are sensitised.Moreover, Kopfschuttel nystaagmus is likely to be a manifestation
      of the horizontal canal stimulation, at leastin some cases, since the movements
      are executed in the plane of the horizontal canal (vide infra) when displaced
      otoconia impinges on the cupula /. crista bringing about its stimulation leading
      to vertigo and or nystagmus.

PMID- 23119887
TI  - Squamous cell carcinoma of the external auditory canal and middle ear results of
      treatment with subtotal temporal bone resection and postoperative radiotherapy.
AB  - Surgical treatment of carcinoma of the ear canal has evolved over the last half
      century. Several approaches are practiced. Primary radiotherapy is practiced in
      only a few centres. The small number of patients seen each year in a given
      centre, the lack of proper staging and the variability of treatment schedules
      used, make comparisons difficult. Twenty one cases of histologically proven
      squamous cell carcinoma of the ear canal seen over a period of 20 years were
      treated with subtotal temporal bone resection and postoperative external beam
      radiotherapy. Tumors were staged preoperatively according to the classification
      suggested by Stell. There were 9 Tl. 7 72 and 2 Ti tumors. Three patients had
      cervical lymph node melastases at presentation. The overall S year disease free
      survival was 42%. Quality of life as regards speech, swallowing, body image and
      social contacts was preserved.

PMID- 23119888
TI  - F. N. A. C. of salivary glands.
AB  - During a period of 12 years, 874 salivary gland lesions were aspirated of which
      740 (86.85%) were from parotid gland. Cystic, inflammatory & neoplastic lesions
      were 25.25%. 54.45% & 20.30%, respectively. Plcomorphic adenoma was the commonest
      benign & adenoid cystic carcinoma was the most frequent malignant tumors.On
      cytohistologic correlation, sensilitvity of cytology for diagnosing cystic,
      inflammatory, neoplastic lesions proved to be 93.3%. 95.7% & 100% respectively.
      Overall accuracy for cytodiagnosis of malignant salivary gland lesions in our
      study was 96.07%.

PMID- 23119889
TI  - Total auricular reconstruction with autogenous costal cartilage framework for
      congenital microtia (grade-III).
AB  - The Auricular deformity of congenital microtia (Grade-llll can cause devastating
      physical and psychological trauma in children. liven crude duplications of the
      normal ear are of great emotional value to the child or adult who is horn with
      only a nubbin. Diverse materials ranging from altografts (polyethylene, nylon
      mesh. Teflon. Silicone,etc), cartilage homo and hcterografts haw been tried for
      framework construction of the ear. Converge (1985) and Tanzer (1959) popularized
      the use of autogenous rib cartilage, carved in a solid block. We describe our
      experience with autogenous costal cartilage graft as framework for total
      auricular reconstruction in 13 patients (15 ears) with congenital microlia(grade
      lll). Atresia repair was performed in two patients. with bilateral grade-Ill
      deformity.

PMID- 23119890
TI  - A clinical study of nasopharyngeal masses.
AB  - Out of 36511 patients attending the ENT OHD of R. G,. Aur Medical Callege &
      Hospital. Kolkata, in one year 0.08% patients were found tuning naspharyngeal
      mass. 30 cases of nasopharyngeal mass were studied. The peak incidence of
      nasopharyngeal mass was in the age group between II to 20 years (40%). The
      incidence in males (73%) was more than females(27%). The maximum ineldence was
      found among students (74%). Commonest ntuopharyngeal nuns teas antrochoanal polyp
      (30%). Next commlon masses were adenoids (23%)Juvenile angwfibroma(20%) and
      nasophartngeal carcinoma (13%). Nasal obstruction was the main presenting
      symptom(83%) followed by epistaxis (40%).

PMID- 23119891
TI  - Tympanoplasty with and without cortical mastoidectomy - a comparative study.
AB  - Perfimttion of the tympanic membrane is nature's may of maintaining the middle
      far vntilation under the pressure of inflammatory process in the tempanomastoid
      cleft. An attempt at reconstruction with the possibility of infection lurking in
      and around the mastoid air cells may seem futile. Vow the quntinn arises as to
      whether a cortical Mastoidectomy is essential before an attempt at reconstruction
      is made. Our experience with one hundred and twenty patients is presented here.
      Our study shovn that conicul mastoidectomy does not signifieantly improve the
      results in well-selected ears.

PMID- 23119892
TI  - Surgical decompression in bell's palsy - our viewpoint.
AB  - Bell's palsv or acute idiopathic lower motor neuron facial palsy is a common
      cause of facial palsy seen in clinical practice. The cause of this disease is not
      exactly known though there arc many theories regarding Ils etiology. In this
      article, we present the theory of "Tertiary is chacmia " in eases of pertinent
      Bell's palsy. Our concept of Tertiary ischaemia is further supported by
      histological findings of the nerve sheath biopsy taken during surgical
      decompression In eases of Bell' s palsy. The procedure, of performing posterior
      tympanotomy and improving the exposure of the middle ear structures therein is
      also explained.

PMID- 23119893
TI  - Uvulopalatopharyngoplasty - surgery for snoring.
AB  - Snoring is a social problem and is considered to be a warning sign, in relation
      to the upper airway structural and physiological anatomy. The complications and
      sequelae of snoring can be life threatening also. Therefore it becomes important
      to treat snoring in the first instance. Surgical treatment of snoring is the
      standard protocol (UPPP) Uvulopalatopharyngoplasty, was started by Fujita a and
      this technique has now been found to be very effective. 8 cases of snoring with
      no evidence of sleep apnta were operated in the department with a standard
      modified technique. The technique und the results are discussed here.

PMID- 23119894
TI  - The role of laser radiation therapy in maxillary sinusitis.
AB  - Efficacy of prescribed noninvasive & invasive types of treatment of maxillary
      sinusitis has been compared with low-dose LASER therapy (LLT). After going
      through the observations of different authors on the therapeutic role of LLT
      (GaA1AS-LASER) in non-ENT infective diseases, its use in 'sinusitis' has been
      adjudged. Such type of study-report has not been found by us in the literatures,
      available to us.It was observed here that the LLT has produced better result with
      better acceptation by patients in the management of 'sinusitis' A LLT-treatment
      virtually produced no side-effect/complication as compared with the invasive
      methods.In this study. 25 cases, treated by LLT, out of 200 cases, treated by
      conventional methods, yielded good result in 22 & satisfactory result in 3 cases.

PMID- 23119895
TI  - KTP-532 laser cordotomy for bilateral abductor paralysis.
AB  - Various lateralization procedures have been described in the past to treat
      bilateral vocal cord paralysis. Though endoscopie lateralization gives good
      results in terms ofdecannulation rates, the postoperative voice quality is often
      poor. KTP-532 laser assisted posterior cordotomy was done in 3 cases. This
      preliminary study showd 100% decannulation rate and good post-operative voice
      quality. The latter was assessed both subjectively and objectively on VAGMI
      scales.

PMID- 23119896
TI  - Pseudoaneurysm of the facial artery.
AB  - Pseudoaneurysm of the facial artery has very characteristic clinical features and
      radiological findings and can be treated with successful catheter emholisation,
      thus decreasing the morbidity associated with surgical procedure. A rare case of
      pseudoaneurysm of the facial artery is presented here for clinical interest.

PMID- 23119897
TI  - Unilateral choanal atresia in a young female.
AB  - Congenital choanal atresia is a rare anomaly with an incidence of one in five to
      ten thousand live births. It can be a bilateral or unilateral atresia; the former
      is a medical emergency while the later may remain unrecognized until later in
      life. Transpalatal or transnasal approaches are routinely followed for surgery
      with placement of stent or serial dilatations in the postoperative period.

PMID- 23119898
TI  - High flow vascular malformations : Review of literature and a case report.
AB  - Vscular malformations are uncommon vascular lama. Low flow malformations hatve
      always been confused with kaemangiamas. Arteriovenous malformations (AVMs) arc
      extremely rure. We present a cue of massive AVM of the head and neck region and.
      disiusstke dlfflculties of cmbotisatim and surgical management in such cases. The
      relevant literature has also been reviewed.

PMID- 23119899
TI  - Cherubism.
AB  - Cherubum is a benign. fanilial giant cell lesion characterised by gradually
      prirgeesive panless swelling of the jaws. A study involving, suffering from this
      rare disarder is preunted. The differentdal dingnosis ON bath clincal
      charcteristics and hisioktical ftvltitgs is disussed. The conficting treatmem
      policlm with respect to non-treatment and surgirai recentouring with curenage,
      are also reviewed.

PMID- 23119900
TI  - Psammomatous extra-calvarial meningioma of the neck.
AB  - A case of Primary extraraniul meningioma of the parapharyngcal space arising
      simulitueouly as two distinct tumour masses from two sepurae cranial nerves is
      reported. The paucity of reported eases is the evidence for its rarily.

PMID- 23119901
TI  - Neurilemmoma (Schwanoma) of the maxillary sinus.

PMID- 23119902
TI  - Pneumothorax following tracheostomy and its management.
AB  - Although pneumothorax is a known complication of tracheostomy, bilateral
      pneumothorax is comparatively rare. The case of suuh a complication is being
      reported here in a patient with a glottic carinoma who underwent emergency
      trackeostamy and developed hilaterluttrl pneuimothoriax and its subsuente.
      management is discussed.

PMID- 23119903
TI  - Elongated styloid process (Eagle's syndrome) & severe headache.
AB  - Elongated styloid process as cause of throat pain & otalgia is common, as found
      in classical Eagle' Syndrome However, elongated styloid presenting with headache
      due to impingement an carotid artery and neurological structures like
      glossopharyngeal nerve, is very uncommon presentation. Here such a case with
      fifteen years of history of being treated as migraine, relieved by styloidectomy
      by Eagte' technique and with a long symptom-free follow up of several years, is
      presented. For the clinician it is important to be aware of such clinical
      variants to successfully diagnose such head & neck pain cases, as resecting them
      surgically, resolves the symptoms completely.

PMID- 23119904
TI  - Benign laryngeal lesions - a clinicopathological study of eleven years and a case
      report of pleomorphic lipoma.
AB  - In a retrospective cohort study, conducted in Department of Oto-Rhinolaryngology,
      Head and Neck Surgery, M.LX Medical College, Allahabad from January 1989 to
      December 1999, 81 benign laryngeal lesions were evaluated. Majority (69, 85.2%)
      presented with hoarseness of voice and stridor was the presenting complaint in 12
      ( 14.8%) cases. Vocal cord polyp (33, 40.7%) dominated the non-neoplastic group,
      while squamous papilloma (18, 22.4%) was the most common neoplastic lesion. Adult
      unset multiple papiUoma of unilateral vocal cord (4, 4.9%) was an unexpected
      finding in our series. A rare case of pleomorphic lipoma of larynx in a 68-year
      old male patient along with its CT characteristics has been presented.
      Conservative microlaryngeal surgery offered the most satisfactory mode of
      treatment without any mortality and with minimal recurrence.

PMID- 23119905
TI  - Effects of vocal fatigue on voice parameters of Indian Teachers.
AB  - Vocal fatigue is a frequently reported voicec symptom among professional voice
      users. Indian School teachers teach lontinuously for many hours in advene
      acoustical environments and are highly susceptible to vocal fatigue. The present
      study is the first to examine acoustic voice measures in teacher, reporting
      naturally induced vocal fatigue. 40 female primary school teachers (mean age =36
      yearn) with varying severity of vocal fatigue participated in this studr. Voice
      measures of minimum and maximum fundametal frequency were obtained before and
      after one and a half hours of continuous teaching at the workplace. Maximum
      fundamental frequent was an important acoustic parameter in determining presence
      of weal fatigue. Most cummin perceptual sympioms include throat dryneis,
      discomfort and loss of voit e. The rule of vocal hygiene and warm-up in reducing
      vocal fatigue are considered.

PMID- 23119906
TI  - Nodal metastases from laryngeal carcinoma and their correlation with certain
      characteristics of the primary tumor.
AB  - 5O cases of carcinoma larynx were included in a prospective study to detect the
      incidence and pattern of nodal metastases (both clinical and occult) and to study
      the influence of certain characteristics of the primary tumor on the incidence of
      nodal metastases. In our study 66% (33 cases) of the lesions were transglottic as
      compared to 24% (12 cases) supraglottic and 10% (5 cases) glottic lesions. The
      most common age group affected in our study was 51-60 years comprising 50% of the
      cases. The most common symptoms were hoarseness, breathlessness and difficulty in
      swallowing. The incidence of clinically positive neck at the time of presentation
      was 42% while the incidence of occult nodal metastases was found to be 27.6%. The
      most common levels of lymph nodes involved in our study were levels II and III
      (87.5% cases). Multiple level lymph node involvement was seen in 71.4% of the
      eases at the time of presentation. A high incidence of cervical nodal metastases
      was associated with the following characteristics of the primary lesion
      extralaryngeal spread, infiltrating or endophytic peripheral growth pattern, poor
      cellular differentiation and advanced T stage. In view of the high incidence of
      occult nodal metastases, use of selective lateral neck dissection is advocated in
      patients with a clinically negative neck at the-time of presentation (early
      glottic carcinomas being excluded).

PMID- 23119907
TI  - A molecular approach (multiplex polymerase chain reaction) for diagnosis of
      rhinosporidiosis.
AB  - A New multiplex PCR have been developed in our laboratory using primer sets,
      aiming amplification of both D.N.A target fragments obtained in 18S RNA of
      commonly encountered fungi in human being and in Rhinosporidium seeberi using F1
      fw/F2-rev (500 bp target) and Rhino-fw/ Rhino-rev (.177 bp target). This
      multiplex PCR has been found to be able to delect R. seeberi from clinical
      samples and differentiate it from other fungi. Furthermore, by this multiplex
      PCR, R. seeberi, phylogenitically appears to belong to a member of so called
      DRIPs clade of fish parasite not a cyanobacterium as claimed previously, by some
      workers.

PMID- 23119908
TI  - Head and neck masses in children: A clinicopathological study.
AB  - Fifty children with head and neck masses were evaluated clinically and
      pathologically. Inflammatory swellings constituted the majority (54%). Congenital
      - developmental malformations were the next common lesions (30%) and neoplastic
      masses constituted the rest (16%). Tuberculous lymphadenitis was found to be the
      single most common etiology (28%). Among congenital-developmental malformations,
      cystic hygroma was the most frequent lesion. The incidence of branchial cleft
      abnormalities was found to be low and no thyroglossal duct cyst was observed in
      this series. Among the neoplastic masses malignant lesions were more common than
      benign tumours and lymphoma was the most common head and neck malignancy
      observed.

PMID- 23119909
TI  - Tympanoplasty in children.
AB  - In this, study, an attempt has been made to find out if the age of the child is a
      factor in influencing the surgical outcome of tympanoplasty. The study group
      comprises 52 children, divided into two subgroups; 8-11 years and 12-15 years.
      The success is defined as an intact tympanic membrane after 6 months of surgery.
      The success rate is slightly higher in 12-15 year age group (90.24%) than in 8-11
      year age group (81.8%). The overall success rate in 86.54% in this series.

PMID- 23119910
TI  - Juvenile nasopharyngeal angiofibromas: A study of recurrence pattern and role of
      pre-Operative embolization - 'a decade'S experience'.
AB  - This study is a retrospective analysis of 30 consecutive cases of Juvenile
      Nasopharyngeal Angiofibroma (JXA) operated at. Department of Head and Neck
      Surgery, Kidwai Memorial Institute of Oncology Bangalore, India: la tertiary
      referral centre) after prior emohilization by an interventional neuro-radiologisl
      (1996-2002). This study discusses critically the planning of surgical approach,
      based on anatomico-radiological factors and highlights the efficacy of
      preoperalive embolization in expediting total re moral of the tumor in 25 out of
      JO cases with advanced stage JNA. OBJECTIVES: To analyze the utility of pre
      operatire embolisation in surgical extirpation of large JNAs; planning of the
      surgical approaches based on CT topography of the tumor; to study the various
      complications of embolisation and surgery associated with JXA & lastly to
      evaluate the puttern and location of recurrent tumor thus correlating with the
      original topography. SETTING: Tertiary care cancer referral centre. PATIENTS:
      PATIENTS ranged in age from ')- 24 years. all being males. INTERVENTIONS:
      Majority of them were accessed by transfacial surgical approach(26). and in the
      recent past via midfacial degloving(4) within 4H hours of angioembolisation.
      RESULTS: Complete removal of the tumor was achieved in 25 out of 30 cases with
      advanced stage JNA.Post surgical CT scans revealed tumor residua in 5
      individuals, where the tumor was documented in - the temporal fossa 12), para
      cavernous sinus region (I), cavernous sinus! I) and pterygo palatine fossa (I).
      Only the lesion in pterygopalaline fossa was successfully re-i>xcised & this
      alongwith the recurrence at para-cavernous & cavernous sinus & another were
      treated with radiotherapy; the 2 cases in the temporal fossa are under
      observation. The average blood loss during the procedure was 546.60 ml.
      CONCLUSIONS: Today, advances in radiologie imaging-complemented by interventional
      neuro-radiological expertise in angio-embolisation have expedited complete
      excision with minimal morbidity and acceptable recurrence rate. This study has
      justified pre-operative embolisation and M currently the standard of care for
      advanced JXA.

PMID- 23119911
TI  - Chronic adenoid hypertrophy in children - is steroid nasal spray beneficial?
AB  - OBJECTIVE: [corrected] To the efficacy of naial btvlomethosone spry in the
      treatmrnl of chronic adenoid hypertrophy in children. METHOD: .-1 randomized
      double-blind placebo-controlled study SETTING: Tertiary academic referral center
      Patients: Aged 3-12 years diagnosed to have chronic nasal obstruction due to
      hypertrophied adenoids. INTERVENTION: Intranasal beclomethasone at the dose of
      200 microgramslday to one group and placebo to the other group in matched
      dispensers for 8 weeks. OUTCOME MEASURES: Reduction of symptoms due to
      hypertrophied adenoids and the size of enlarged adenoids. Variables were noted at
      the beginning and end of the study for symptoms score severity. X-ray and
      flexible nasal endoscopie findings. RESULTS: Analysis was done to find any
      significant improvement between the two groups. The Chisquare test was used to
      investigate the relationship between discrete variables. 26 children completed
      the study with 13 each in the drug and placebo group. There were 17 male and 9
      female patients from 3 to 12 years of age. There was no significant difference in
      nasal obstruction, snoring or nasal discharge between the two groups. Comparison
      of x-rays and endoscopy also showed no significant difference between the 2
      groups significant (P value =1.000 and P=0.0666 respectively). CONCLUSION: This
      study indicates that intranasal beclomelhasone therapy is not useful in treatment
      of ehronic adenoid hypertrophy in the general pediatrie population.

PMID- 23119912
TI  - Hearing profile in hypothyroidism.
AB  - The present study was carried on forty-five patients of confirmed hypothyroidism.
      Complete clinical examination and laboratory investigations were done regarding
      audiological and vestibular system. It was found that hypothyroidism affects the
      ear at multiple sites producing various types of hearing impairment viz.
      conductive, sensorineural and mixed. Vestibular system was found to be affected
      only minimally. The patients were then given levothyroxine and follow-up was done
      when they were euthyroid, which revealed statistically significant improvement in
      hearing threshold in 30% ears, in which conductive impairment was more common to
      be improved. The middle ear compliance and pressure, on impedance audiometry,
      also improved significantly in 50% and 87.50% ears respectively. Statistically
      significant change was also observed in acoustic reflex threshold. Improvement
      was also noted in wave I, V and interpeak (I-V) latencies, on Brain stem Evoked
      Response Audiometry (statistically not significant). The results of auditory
      investigations suggest a causal relationship between hypothyroidism and hearing
      loss. The site of.

PMID- 23119913
TI  - Topographical distribution of laryngeal carcinoma - A study of fifty cases.
AB  - Regional and site-specific distribution of fifty cases of Laryngeal carcinoma is
      presented along with a review of the avialable literature.

PMID- 23119914
TI  - A Study of incidence and etiopathology of vocal cord paralysis.
AB  - Vocal cord paralysis is not a disease per se but is considered as a sign of
      underlying disease process that may be congenital or acquired, unilateral or
      bilateral, sudden or gradual in onset, and may occur at any age from cradle to
      the grave.This study vas carried out to know the incidence and etiopathology of
      vocal cord paralysis.The incidence was 0.42% or 42 per ten thousand new patients
      seen. Most patients presented in the 5th and 6th decades (77.2%). Males
      outnumbered females in the ratio of 3:1. The most common symptom of vocaL cord
      paralysis was hoarseness of voice alone(83.6%.).Onset of symptoms was gradual in
      60% of cases.Left vocal cord was almost twice more commonly (61.9%)involved than
      the right one(38.1%).Idiopalhic group constituted 38.18% of patients followed by
      neoplaslic diseases 29.09oc.

PMID- 23119915
TI  - An unusual case of impacted oesophageal foreign body.
AB  - Impacted sharp foreign bodies in the oesophagus can be very difficult to manage.
      When attempts are made to remove such objects inappropriately, life-threatening
      complications such as oesophageal perforation can occur. We hare reported a rare
      case of impacted denture in the oesophagus where endoscopic removal was not
      possible due to the perforation already caused by the denture, sinee this would
      have caused an oesophageal laceration, which could have proved fatal. Hence
      surgical removal had to be performed with repair of the oesophageal perforation.

PMID- 23119916
TI  - Tuberculous mastoiditis.
AB  - A 14 month old child with intractable painless otorrhoea resistant to
      conventional treatment with sadden onset facial palsy was referred to us for HRCT
      of temporal bone. A rare diagnosis of tuberculous mastoiditis was made which was
      confirmed by histopathological reports. In this case the use of a Multislice CT
      scanner (Siemens Volume Zoom) in demonstrating the intricate involvement of the
      middle and inner ear structures by the disease is accentuated.

PMID- 23119917
TI  - Third pinna in nasopharynx-a rare case of mature teratoma.
AB  - Tertomas are the rarstf natopharyngcal swellings detected. they arise. during
      early embryogenesis and are being derived from all three germinal layers. They
      usually present at or soon after the birth with features of upper aerodigestive
      tract obstruction. A case of mature tratoma of nasopharynx in the shape of a
      pinna with presence of two other pinna at their normal anatomical site is
      reported here. The etiology of teratoma, classification, clinical features and
      management are discussed.

PMID- 23119918
TI  - Malignant melanotic schwannoma of maxilla.
AB  - Malignant schwannoma in the naso-maxillary region is very rare. Only 20 eases
      have been reported in the literature (Maheshwari et al 99) Melanotic variety of
      this tumor is extremely rare and only 4 cases have been found in internet search.
      Surgery followed by radiotherapy has been advocated for treatment. A case is
      reported involving maxilla in a 13 year old female patient because of its extreme
      rarity. The case was treated by surgery and showed no recurrence during a 3 year
      follow-up period.

PMID- 23119919
TI  - Aneurysmal bone cyst of paranasal sinuses.
AB  - Aneurysmal hone cyst is rare in paranasal sinuses. It may be uni or multilocutar
      It occurs alone or with other benign bone lesions. The exact pathogenesis of it
      is still unknown. The aggressiveness of the disease needs early diagnosis and
      proper management to prevent recurrence. This report describes a case of
      aneurysmal bone cyst involving the ethmoid and maxillary sinuses which was
      successfully managed.

PMID- 23119920
TI  - Interesting case of frontal sinus injury.

PMID- 23119921
TI  - Solitary extramedullary plasmacytoma - larynx.
AB  - Solitary Plasmacytoma of the larynx is a rare tumor with male predominance and
      most patients are between 50-70 years of age. The paper reports a case of
      Solitary Extramedullary' Ipasmacytoma. (EMP) ljirynx in subglottic region, in a
      65-year-old man successfully treated with complete response to radiotherapy.

PMID- 23119922
TI  - Mucociliary function of eustachian tube in atrophic rhinitis.
AB  - Atrophic rhinitis is a chronic inflammatory disease characterized by progressive
      atrophy of nasal mucosa and underlying turbinate bones. Atrophie changes may
      extend to the nasopharynx and subsequently Eustachian tube and middle ear system
      may also get involved. Mucociliary function of the Eustachian tube In cases of
      atrophie rhinitis has been measured by saccharine tut and 17.46% of cases showed
      a delayed clearance time. All these cases had prolonged duration of symptoms with
      advanced stage of the disease.

PMID- 23119923
TI  - The relative sensitivity of barium swallow examination.
AB  - In all the cases of P.V Syndrome, it is better to find out by endoscopy even if
      barium swallow is normal. Thus in P. V. syndrome, the accuracy of barium swallow
      is only 19% and 81% are reported as false negative.In strictures and
      malignancies, the level of lesion reported by barium swallow should not be relied
      upon in all the cases, and they should be confirmed by endoscopy.Endoscopy
      provides us with a definite diagnosis and allows biopsy and hence histological
      confirmation. Barium Swallow is an important examination that can be used to rule
      out certain lesions. So endoscopy can be avoided in these patients. Failure rate
      of Barium Swallow can mostly.

PMID- 23119924
TI  - Halogen head light-you can make it.
AB  - Halogen head light can be made by removing the ordinary bulb and its attachments
      from the Clark's tike head light and replacing it with Halogen tube (12 volts 55
      watts) along with its attachment. This Halogen tube needs 12 volts 5amp
      transformer for its maximum output.

PMID- 23119925
TI  - Aesthetic rhinoplasty: Changing trends.

PMID- 23119926
TI  - Reconstruction of complex oral defects using bi-paddle pectoralis major flap -
      technical modifications and outcome in 54 cancer patients.
AB  - OBJECTIVE: Reconstruction of locally advanced oral cancer presents a great
      challenge to the head and neck surgeon. The main goal of reconstruction is to
      provide intraoral lining and soft tissue cover. We discuss the use of Bipaddle
      pectoralis major myoculaneous flap (PMMF) and its modifications for
      reconstruction of complex oral defects following radical resection. STUDY DESIGN:
      Retrospective analysis of prospective oral cancer data base. SETTING: Tertiary
      Care Regional Cancer Center. PATIENTS: Three hundred and ten patients were
      operated for oral carcinoma in this unit between 1993 and 2001. The oral cancer
      patients who required soft tissue reconstruction for lining and cover were
      analyzed. Patients in whom bipaddle PMMF were utilised were studied in terms of
      surgical technique, morbidity, function and cosmetic outcome. RESULTS: Ninety-one
      (29.4 %) oral cancer patients required reconstruction for lining as well as
      cover. Of these, 54 (17.4 %) patients underwent a bipaddle PMMF flap
      reconstruction. Two horizontal skin islands were used in patients with lateral
      defects and two vertical islands in patients with central defects. There was no
      complication in 41 (76%) patients. Complete flap loss was seen in only one
      patient and differential flap loss in 2 patients (4 %) while seven (13 %)
      patients had only minor complication. All the patients received post-operative
      Radiotherapy. Good to average functional and cosmetic outcome was observed in 90%
      patients. CONCLUSIONS: Bipaddle PMMF offers an effective and leliahle
      reconstructive option for complex oral defects. By using certain technical
      modifications, majority of complex oral defects can be managed successfully using
      a Bipaddle PMMF. In a developing country like India with a large oral cancer
      disease burden Bipaddle PMMF should he used routinely for complex oral defects in
      view of its simplicity, versatility and reliability.

PMID- 23119927
TI  - Retrospective and prospective study of head and neck cancer.
AB  - A prospective clinico pathological study of Head and Neck Cancer cases presenting
      in E.N.T. OPD was done and its observations were compared with retrospective
      studies done earlier by Gupta et al (1986), It was seen that carcinoma
      laryngopharynx was the commonest (38.18%) malignancy seen in the present study
      followed by carcinoma of Larynx (16.36%) and Oesophagus (14.54%). Carcinoma of
      the nasopharynx was seen in 12.72% cases followed by carcinoma oropharynx
      (10.91%), Histopathologically; 98.18% cases were of squamous cell carcinomas and
      out of these only 31.48% were well differentiated carcinoma. There was only 1
      case (1.81%) of occult primary. In the retrospective study, the incidence of
      cancer of Laryngopharynx was 33.33% followed by oropharynx 16.66% and Larynx and
      Lymphoma (11.11%) each. Occult primary was observed in 3 cases (5.33%) and
      carcinoma naspoharynx in 4 cases (4.44%). Poor socioeconomic status, bad
      orodental hygiene, Plummer-vinson syndrome in females were the commonest
      predisposing factors in addition to smoking, Pan Masala, Zarda and Gutka chewing
      in the causation of Head and Neck cancer both in prospective and retrospective
      studies.

PMID- 23119928
TI  - Rhinitis caseosa, nasal cholesteatoma and allergic fungal sinusitis.
AB  - The recently described Syndrome of Allergic Fungal Sinusitis (AFS) has many
      similarities with the previously described entity of rhinitis Caseosa (synonym
      Nasal Cholesteatoma). 28 patients treated over a 6 year period with a diagnosis
      of rhinitis caseosa/nasal cholesieatoma have been retrospectively reviewed with
      regard to their clinical and radiological features, operative findings and
      microbiologic and histopathologual features.All cases presented with nasal
      obstruction and nasal polyposis. CT scanning indicated intracranil extension and
      intra-orbital extension m 9 cases each. Surgical debridetnent with establishment
      of sinus drainage led to the universal initial relief of symptoms in all cases.
      26 of 28 cases have remained free of recurrence on prolonged follow-up (minimum
      follow-up one year).Despite these cases demonstrating clinical, radiologital,
      morphological and histological similarities with the Syndrome of Allergic Fungal
      Sinustitis, in only 2 cases was a fungal aetiology confirmed by history. The
      clinical syndrome of "Rhinitis Caseosa" is described and its relationship with
      the Allergic Fungal Sinusitis (AFS) syndrome and the "AFS-hke" Syndrome explored.

PMID- 23119929
TI  - Chronic suppurative otitis media and sensorineural hearing loss: Is there a
      correlation?
AB  - Traditionally, it has been accepted that chronic suppurative Otitis media is
      associated with a breakdown in meekanical conduction of sound leading to
      conductive hearing loss, On;the contrary, there are two schools of thought when
      it come, to the issue of cpchlear involvement leading to sensorineural hearing
      loss (SNIIL) in chronic suppura the Otitis media. The present study was
      undertaken to find out whether a sensorineural component exists in hearing loss
      associated with chronic suppurative otitis media, A sample of 100 patients of
      unilateral chronic suppurative otitis media was selected for the Study and their
      bone conduction thresholds Mere analyzed in relation to the duration of disease
      using audiometric data. A 24 per cent incidence of sensoineural hearing loss was
      found in this series, garticularly involving the higher frequencies. Moreover,
      the incidence of sensorineural hearing loss progressively increased with the
      increase in duration of chonic suppurative Ouns meadia.

PMID- 23119930
TI  - Tobacco and alcohol consumption in relation to oral cancer.
AB  - The present case control study was done on 50 cases of oral cancer and 50
      controls These two groups are compared after taking the history in detail with
      special emphasis on the tobacco and alcohol intake. My various statistical tests,
      we correlated the strength of association between tobacco/alcohol intake and
      development of oral cancer. Tobacco only and combined exposure to tobacco and
      alcohol was found to be strongly related to the development of oral cancer but
      alcohol alone does not have significant role in causation of oral cancer.

PMID- 23119931
TI  - Myxoma of maxilla.
AB  - A case of Myxoma involving left Maxilla, presenting as swelling of left side of
      face and Oral cavity with bilateral nasal obstruction is reported.

PMID- 23119932
TI  - Tuberculous granuloma in haemangiomatous nasal polyp.
AB  - Tuberculosis of upper respiratory tract is quite infrequent especially the nasal
      involvement. Isolated cases have been reported by certain authors. A ease of
      nasal tubercolosis is being presented for its rare site and its association with
      haemangioma.

PMID- 23119933
TI  - True glottic foreign body in an infant.
AB  - A case of true glottu foreign body (metallic blouse hook) Sandwiching the vocal
      cord reported here in an 8-months-old infant who presented with abnormal cry.
      only. In the absence of classical history and clinical features, a laryngeal
      foreign body should be suspected in otherwise healthy child with abnormal cry The
      difficulties and ountet cd and potential risk of complicattions during the
      removal are discussed.

PMID- 23119934
TI  - Schwannoma of the nose and paranasal sinuses.
AB  - Sckhwannoma is a benign tumor arising from the Schwann cells of nerve
      sheath.Through they arise more commonly in the head and neck than other regions,
      a through search in the liturature including medline revealed only about 47
      reported cases of schwannoma in the paranasal sinuses of which the maxillary
      sinus involvement is more common. We report three cases of schwannoma arising
      from unusual sites in the paranasal sinuses with different modes of presttation
      each requiring a specific approach for surgical excision Transnasal endoscopic
      approach in combination with vonventional approaches is of immense value in the
      surgical management of these benign lessions of the paranasal sinuses.

PMID- 23119935
TI  - Osteoclastoma of temporal bone.
AB  - A 20 year male presented with a gradually increasing painless swelling at right
      temporal region with progressive hearing loss conductive in type. On plain X-ray
      a wide radio translucent area of bone destruction was noted. The mass was excised
      as much as possible via post-auricular incision extending antiriorly toward the
      zygomatic root.Histopathological examination showed the features suggestive of
      osteoclastoma. Post-operative radiation was administered to deal with the
      remaining mass there was no recurrence of growth even.

PMID- 23119936
TI  - Adenoid cystic carcinoma of nasal cavity - a case report.
AB  - A 38 year old male patient presented with pain and swelling on left side of nose
      with mass in left nostril. The other symptoms were nasal obstruction, epistaxisc
      from left nostril and epiphora from left eye. CT scan showed a mass arising from
      lateral wall of nose on left side eroding anterior part of medial wall of
      maxillary sinus. The tumor was excised with wide margin through a lateral
      rhinotomy approach under general anaesthesia. In histopathologieal examination it
      was found to be cribriform type of Adenoid Cystic Carcinoma. This case is
      reported here for its rarit.

PMID- 23119937
TI  - Otological manifestations in head injury and their management - a case report.
AB  - 32 year old male presented with right facial palsy following head injury.
      Clinical evaluation showed hemotympanum on right with moderately severe
      conductive hearing loss, grade III LMN facial palsy and BPPV. HRCT of temporal
      bone demonstrated fracture base of skull involving the roof of mastoid with no
      evidence of bony injury to fallopian canal. Conservative management of head
      trauma resulted in satisfactory outcome except for conductive hearing loss and
      faciel palsy. Facial palsy was managed conservatively [physiotherapy and oral
      steroids] with full recovery of function after 4 weeks. Conductive hearing loss
      was managed by combined approach tympanaplasty. Preoperutively incudostapedial
      joint dislocation and fracture anterior crus of stapes were noted. Type II
      tympanoplasty with horizontal incus repositioning was carried out.PTA after 6
      weeks showed 15-20 dB air-bone gap compared to 50-55dB air-bone gap
      preoperatively. BPPV recovered spontaneously. This case is reported to
      highlight:Importance of imaging of temporal bone.Spontaneous recovery of facial
      nerve function in neuropraxtc injury.Timely and appropriate surgical intervention
      of ossicular damage following head injury resulting in satisfatctory outcome.

PMID- 23119938
TI  - Reconstruction of mandible with free fibular vascular graft.
AB  - This is a case report of ameloblastoma of left mandible. It was treated with left
      extended hemimandibulectomy with free fibular vascular graft.

PMID- 23119939
TI  - Internal maxillary artery ligation for idiopathic intractable epistaxis.
AB  - Epistaxis though common, is rarely life threatening. Routinely nose pinching,
      anterior find posterior nasal packing and endoscopic cauterization of bleeding
      points is sufficient to control epistaxis in 99% of the cases. It is mandatory to
      rule out local and systemic causes before labeling a case as idiopathic by using
      a battery of investigative modalities. Here are two interesting cases of
      epistaxis which did not respond to conventional therapeutic modalities in which
      transantral internal maxillary artery ligation was attempted leading to complete
      cure.

PMID- 23119940
TI  - Oesophageal candiasis in AIDS.
AB  - With the explosion in the number of AIDS patients, many of these are likely to
      consult to otolaryngologists the head & neck is a rather common site to be
      affected. Sometimes only oesophageal candidiasis is the presenting feature as in
      the present case which is being reported show typical radiological appearance.
      the differential diagnosis and treatment of nesophageal candidiasis is briefly
      discussed.

PMID- 23119941
TI  - A practical cochlear implant for India.
AB  - The present studywas done to evaluate the performance of short electrode, single
      channel, low cost cochlear implant working with analogue strategy.Both prelingual
      and post lingual patients were selected for the study. Results were assessed
      using standard protocol established by us evaluation of these patients in the
      local languagues.For two years follow up, overall results for post lingual
      patients are satisfactory.Incase of prelingual patients results are very
      encouraging as well.If we consider the cost v/s. the performance, these low cost
      implents can be the ideal implant for the Indian patients.

PMID- 23119943
TI  - Identifying & managing the deaf child - are we doing enough?

PMID- 23119942
TI  - Care of lingual vessels during surgery over floor of mouth.
AB  - The lingual vessels and its branches being superficial at under surface of tongue
      and floor if mouth may get injured during surgery over of floor of mouth.In two
      cases, lingual vessels were severed accdentally during surgery with excessive
      haemorrhage. This study was done to care the lingual vessels during surgery. Four
      main surgical dangerzone are found and emphasis is being given to be over
      cautious while operating over this surgical danger zones.Surgery over the floor
      of mouth is done in a number of conditions. Lingual vessels being very
      superficial, its sub-lingual branches are damaged during surgery if surgeon is
      not cautious and may create problems.To avoid this, thorough knowledge of correct
      surgical anatomy, course & relation of lingual vessels and floor of mouth is
      essential.

PMID- 23119944
TI  - Nasal manifestations in chromium industry workers.
AB  - People working in mines, plating factories, cement industries are mainly exposed
      to chrome substances, IIexavalent chromium has been implicated for its toxic
      effect on the nasal mucosa. Hereby we present a rare study of 28 patients who
      attended out patient department of Otorhinolaryngology at SSG Hospital, Baroda
      from a nearby chromium industry. This study aims to present various nasal
      manifestations of toxic effects of prolonged chromium exposure.

PMID- 23119945
TI  - Nasal mucociliary clearance in patients with tracheostomy.
AB  - Nasal mucociliary clearance (NMC) time was estimated in 30 tracheostomized
      patients (24 males & 6 females) in the age group of 13-55 years which was 7.04+/
      0.38 minutes: The patients suffering from nose and paranasal sinus disorders;
      taking drugs like bromhexine; undergoing radiotherapy and smokers were excluded
      from the study. The nasal mucociliary clearance in 30 age & sex matched healthy
      controls was 9.16+/-0.62 minutes. The NMC was found to he significantly lowered
      in patients with tracheostomy (p<0.01). This decrease in NMC tune was significant
      in tracheostimized patients of more than 3 weeks duration (p<0.01), whereas, it
      was not found significantly lowered in patients with tracheostomy of less than 3
      weeks duration (p>0.1).

PMID- 23119946
TI  - Throat swab culture & sensitivity reports - an overview.
AB  - 305 throat swab culture & sensitivity reports were reviewed from the records of
      Microbiology department of Shri V.N. Govt. Medical College, Yavutmal. 130 reports
      were showibetag, growth of pathogenic organisms. Out of this, 771 eports were
      showing coagulase positive staphylococci; 32 were showing group A b haemolytic
      streptococci. A bimodal peak of pathogenic organism growth was observed in the
      month of March and from August to October. Analysis of culture and sensitivity
      reports, showed that amongst many, erythromycin - a time tested, comparatively
      cheap and reliable drug - has very good sensitivity spectrum. Cefotaxime,
      tetracyline, penicillin and gentamicin were also found to be useful. Emerging
      resistance to some newer antibiotics is a matter of concern and hence authors
      advocate the formulation of effective antibiotic policy at the national and loco-
      regional levels.

PMID- 23119947
TI  - Auditory neuropathy : Diagnostic and therapeutic challenge report of first series
      of four cases from india.
AB  - Auditory neuropathy (AN), a recently described clinical entity, is a
      sensorineural disorder where the patient has hearing loss with impaired word
      discrimination out of proportion to pure tone loss in the pressence of abnormal /
      absent auditory brain stem responses, and normal outer hair cell as measured by
      otoacoustic emissions and / cochlear microphonics. It is essential that the
      practicing, ENT surgeon have a high degree of suspicion of AN in patients
      complaining of difficulty in understanding speech with hearing loss and
      audiological evidence of dissociation between pure-tone and speech audiometry.
      Appropriate newer diagnostic tests of ABR and OAE and /or CM for confirmation of
      AN is essential. We present a series of four patients with auditory neuropathy
      from a tertiary care teaching hospital. This is the first Series of 4 cases of
      this clinical entity from the Indian subcontinent.

PMID- 23119948
TI  - Management of laryngotracheal stenosis using dilatation and stenting.
AB  - 14 patients of chronic lai yngotracheal stenosis were studied They underwent
      dilatation land stenting follonmg GO laser excision of the stenotic segment 70%
      patients had improvement in airway and voice was improved in 64% of the patients.

PMID- 23119949
TI  - Stylalgia and its surgical management by intra oral route -clinical experience of
      332 cases.
AB  - Stylalgia is a pain syndrome occurring in connection with on elongated or
      malpositioned styloid piocess and is more common than generally thought. 332
      cases of stylalgia were diagnosed over a period of 15 years. The charcteristic
      symptoms were chronic throat pain during swallowing with referred otalgia or
      referred pain to cheek or lower part of neck associated with foreign body
      sensation in throat. Movements of head or act of deglutition initiates or
      increases the pain The diagnosis of stylalgia is based on symptoms, palpation of
      enlarged styloid process mtraorally in the tonsillar region and elicitation of
      similar nagging throat pain or pain in the neck or foreign body sensation in the
      throat. Confirmation of enlarged styloid process is always done by radiological
      examination of styloid process per orbital view. Bilateral enlargement of tyloid
      process were found in 196 patients (59.03%) and unilateral enlargement was found
      in 136 (40.96%) patients. All the patients were operated under local anaesthesia
      by intra oral route without any complications.

PMID- 23119950
TI  - Cervical lymph node metastases in head & neck malignancy - A Clinical
      /ultrasonographic/ Histopathological comparative study.
AB  - A study was conducted on the value of Ultrasound (US) in the detection of
      cervical lymph node metastases in cases of Head and Neck malignancy; and its
      usefulness in planning surgical management. The clinical, ullrasonographic and
      histopathological examination (HPE) findings were compared in 20 patients as a
      preliminary assessment of this ongoing study. Clinically and
      ultrasonogiaphically, patients were assessed for presence of nodes, their size,
      shape, mobility and overall positivity for malignancy. All patients then
      underwent neck dissection, and individual nodes from the specimens were assessed
      by HPE.It was found that US, when compared with clinical examination had a
      sensitivity of 47.62% versus 43.75%, specificity of 77.78% versus 25.0% and an
      accuracy of 61.54% as opposed to 38.9%. US proved valuable in detecting sub
      clinical nodes, central necrosis, extra-capsular spread, pressure on large
      vessels - all indicators of metastatic spread. Hence, US was found to be
      efficient and cost-effective pre-operatively, in planning surgical management.

PMID- 23119951
TI  - Concurrent cisplatin and radiotherapy in advanced head and neck cancer.
AB  - Management of Head and Neck Cancers poses a challenge inspite of several advances
      because of poor success in terms of response rate, survival and reduced morbidity
      of the patients. In the present study 30 untreated histologically proven cases of
      head and neck cancers were subjected to weekly radiotherapy with adjuvant
      chemotherapy (cisplatin 30 mg/m(2) intravenously). This study group was compared
      with a group of 30 patients who were given only radiotherapy. Results have shown
      that combination of chemotherapy with radiotherapy gives a significantly better
      results in tumour as well as nodal response with minimal toxicities.

PMID- 23119952
TI  - Ondansetron and dexamethasone in middle ear procedures.
AB  - A randomised, double-blind study was conducted on 90 ASA I & II patients
      undergoing middle ear surgery to compare the efficacy of ondansetron,
      dexamethasone and a combination of Ondansett on+dexamethasone for the prevention
      of postoperative nausea and vomiting. Group I patients received ondansetron (0. 1
      mg/kg), group IIpatients received dexamethasone(0.1z mg./Kg) while group III
      received ondansetron (0.1 mg./kg) + dexamethasone (0.15 mg/kg), 10 minute before
      induction of general anaesthesia. A standardised general anaesthetic technique
      was employed through out. A complete response, defined as no postoperative nausea
      and vomiting and no need for another rescue antiemetic during the first 4 hours
      after anaesthesia was achieved in 58%, 55% and 83% of patients who had received
      ondansetron, dexamethasone and ondansetron + dexamethasone respectively. The
      corresponding incidence during the next 20 hours after anaesthesia was 54%, 47%
      and 85%. No clinically important adverse effects were observed in any of the
      groups. We conclude that prophylactic therapy with ondansetron +dexamethasone,one
      is superior in the prevention of postoperative nausea and vomiting after middle
      ear surgery.

PMID- 23119953
TI  - Retraction pockets in chronic suppurative otitis media- our experience.
AB  - Retractions of the tympanic membrane constitute a large proportion of ear
      diseases causing concern to the otologist. The clinical features in a case of
      retraction pocket are varied and cholesteatoma. Also, that a retraction pocket in
      the posterosuperior region and pars ftaccida is a precursor of cholesteatoma is
      now well recognized. We have studied 60 cases of retraction pockets during a
      period of 5 years and have attempted to find out the etiology as well as the most
      effective treatment in such cases. Though over the years along with a
      dysfunctional eustachian tube, a sclerotic mastoid has been implicated as one of
      the causes of Retraction Pockets, we in our study have seen a large sized mastoid
      antrum (beyond 2 mm vf Lateral Semicircular Canal) as a consistent feature in
      most of our cases. This was subjectively assessed as a surgical finding in
      tympanomastoidectomy and objectively assessed by a high Resolution Computed
      Tomography of the temporal bone. We have found that a canal wall down
      mastoidectomy was the most effective in preventing the recurrence of retraction
      pockets. In a coutry like India, canal wall down mastoidectomy offers an
      acceptable solution to the problem of retraction pocket as not only is the follow
      up of patients poor but also the "Second- Look" procedure is not always possible.
      The use of 1- 0 chromic catgut in the middle ear instead of the more
      conventionally used silastic in preventing recurrent retractions can be
      considered as an effective single-staged procedure.

PMID- 23119954
TI  - Osteopetrosis-variable otorhinolaryngological manifestations.
AB  - Osteopetrosis is a rare hereditary metabolic disease associated with a myriad of
      otolaryngological presentations. Three cases with varying otolaryngological
      presentations are described here. A brief review of the radiological changes of
      interest to the otorhinolaryngologist is being made.

PMID- 23119955
TI  - A bullet in the parapharyngeal space.

PMID- 23119956
TI  - Tuberculosis of tonsil - a rare site involvement.
AB  - Tuberculosis of Tonsil and Oropharynx are almost a forgotten condition now- a-
      days. Persistent sore throat, ulcer over tonsils and unilateral tonsillar
      enlargement should arose suspicion of tubercular infection. Confirmation oj which
      depends on histopathology favouring tuberculosis and /or AFB positivity on
      tonsillar tissue. Condition is curable with proper Anti- TB treatment with or
      without tonsillectomy, A case is presented considering its rarity.

PMID- 23119957
TI  - Sinonasal tuberculosis in diabetics : An unusual presentation and diagnosis.
AB  - Sino-nasal Tuberculosis constitutes 5-6% of Head & Neck tuberculosis1. We present
      two cases of sino-nasal tuberculosis in diabetic hosts not only due to the
      clinical rarity and unusual presentation as in one case which presented with
      subperiosteal abscess, but also to emphasize on the effective modality of
      management which constituted transnasal endoscopic clearance supplemented with
      antitubercular regimen.

PMID- 23119958
TI  - Inverted papilloma of nose with orbital involvement and malignant transformation.
AB  - We report two cases of inverted papilloma of nose with malignant transformation
      and orbital involvement in 60 year and 73 year male patients from Nepal. Medial
      maxillectomy and orbital exenteration were done in both cases. Histo-
      pathological examination showed areas of squamous cell carcinoma in inverted
      papilloma in both of the cases.The dilemma of diagnosis and treatment is
      discussed with review of literature.

PMID- 23119959
TI  - Oropharyngeal herpes simplex in an adult.
AB  - Herpis simplex 1 infection involving the orophaiynx in an adult is a rare entity,
      as, primary infection with type I herpes simplex is commonly seen in children and
      c auses a severe vesicular and ulcertive stomatitis and occasionally spreads to
      the oropharynx.

PMID- 23119960
TI  - Congenital cystic lesions in head and neck.
AB  - Congenital lesions by definition are present at birth; but certain congenital
      lesions of the head and neck, like branchial cysts and dermoid cysts, clinically
      present in childhood, early adulthood or late in life. A good history and a high
      degree of suspicion are the key to the adequate management of such lesions. Here
      we present a series of six case reports of congenital cystic lesions of the head
      and neck.

PMID- 23119961
TI  - Vallecular cyst.

PMID- 23119962
TI  - Schwannoma of maxillary sinus.
AB  - Schwannoma, also known as neurilemmoma, is a solitary, encapsulated peripheral
      tumour of neuroectodermal derivation that originates from schwann cells of neural
      sheath of motor/ sensory peripheral nerves or sympathetic nerves. About one-
      third of all schwannomas occur in head and neck region but nose and paranasal
      sinuses, are rare sites. We report a case of schwannoma arising from the
      maxillary sinus and eroding the orbital floor. To the best of our knowledge, this
      is the sixth; case of schwannoma solely arising in the maxillary sinus, reported
      in the literature.

PMID- 23119963
TI  - Aid for impacted foreign body ear.
AB  - Foreign body ear is a common problem. When it is impacted it can tax the resorces
      of each of us. An attempt is made in this paper to make a customable foreign body
      removal hook using a lumbar puncture needle.

PMID- 23119964
TI  - Pediatric cochlear implantation-I : Candidacy.
AB  - The cochlear implant is a successful means of intervention to facilitate the
      perception of sound and oral communication for children with severe to profound
      sensorineural hearing loss. Often, the cochlear implantation process is viewed as
      being limited to a surgical procedure, rather than an entire process of medical,
      audiological, psychosocial, educational and therapeutic, management. In India,
      cochlear implantation is available in only a few large cities. Here, the
      otolaryngologist will direct the cochlear implant programme. Besides
      determination of medical candidacy, device implantation and medical management,
      the otolaryngologist is responsible to ensure that other aspects of cochlear
      implant management are implemented. This paper, the first of two that describe
      the multidisciplinary, team approach of the Pediatric Cochlear Implant Program of
      The Children's Hospital of Philadelphia (CHOP), in Pennsylvania, USA, discusses
      the non-medical aspects of cochlear implant candidacy. A second article will
      follow that covers post-implantation follow- up. The various speech tests used at
      CHOP for assessment are based on the English language. They may be translated
      into the regional Indian languages where the assessment and training can be
      carried out accordingly.

PMID- 23119965
TI  - Neurofibroma-a call for public awareness.

PMID- 23119966
TI  - CT guided fnac of nasopharynx: A new diagnostic tool for early and rapid
      detection of Nasopharyngeal Carcinoma.
AB  - Early detection of nasopharyngeat carcinoma (NPC) still remains a. ekalleng to
      the clinicians because of its nonspecific early signs and symptom, difficulty in
      the eramaation of the nasopharynx and also becuase of the disease's early loco-
      regional spread. For an.early and rapid detection of this diseas a new diagnostic
      fool- CT guided FNAC of nasopharyns is interdadeced here in the diagnostic
      armamentarium of the head and neck cancers. In this prospective study 30
      clinically suspectedcases of NPC are subjected to this new diagnostic tool along
      with tht other dignastic measures like radiological and pathological studies. The
      technique is found to be quite reliable in the diagnosis of NPC with a
      sensitivity of 63.2% and. a specificity of 100% The overall actaracy of the
      technique is 76.7% This, novel technique is fast and reliable, well tolerated by
      the patients with few complications, and if performed properly, can contain costs
      while maintaining high dianastic efficency.

PMID- 23119967
TI  - Role of autografts in the reconstruction of ossicular chain in intact canal wall
      procedures.
AB  - Improvement of hearing in ossiculoplasty depends on the efficiency of the methods
      to reestablish the ossicular continuity and the connection with the tympanic
      membrane. While various prostheses have been used to bridge the ossieular defect,
      we have used autogenous bone (incus remnant & cortical bone ) and autogenous
      cartilage (frugal & conchal) for reconstruction of ossicular continuity.Hearing
      results at I8 months follow up have been fairly good i.e., 84% patients had
      closure of air bone gap within 20 dB and 37% had closure of air bone gap within
      10 dB.

PMID- 23119968
TI  - A Clinico-pathological study of Reinke'S oedema.
AB  - An analysis of 92 eases of Reinke's oedema was done in this study. It wen most
      often seen in middle-aged persons. A Male predilection (57%) was found. In 68
      (74%) cases, the lesions were unilateral and in 24 (26%) teses, the lesions were
      bilateral. Smoking (83%), vocal alms or misuse (80%) and chromnic respiratory
      tract infection (43%) were the main aetiological factors. No significant
      relationship of reinke's oedema with hypotkyroidsm was found. There were no
      dysplastic changes in the epithelium The treatment of reinke's oedema is a
      combination of surgery and vocal rehabilitation. Conventional microlaryngeal
      surgery is ideal for the treatment of Reinke's oedema. Acquired laryngeal web
      involving the anterior part of the vocal cords may develop if stripping of the
      both vocal cords is performed carelessly. Operating measures do not prevent
      recurrences of Reinke's oedema. Voice therapy and cessation of smoking in the
      postoperative period play important roles in the long term treatment results of
      Reinke's oedema.

PMID- 23119969
TI  - Osteoma of the paranasal sinuses.
AB  - Osteamas of the paranasal sinuses are rare, They often appear as a coincidental
      finding on X-ray in patients having radiographs for same other reasons.
      Tomographic evaluation is the mainstay surgical access and its subsequent follow
      up. We report a series of 20 cases of osteamas of the paranasal sinuses who
      underwent surgery for their symptoms. Wide exposure at surgery is necessary for
      complete or near complete removal. Tumour close to the dura, optic-nerve and
      internal carotid artery may be left Close and long period offollow-up is
      essential, especially when the tumour is partially left behind. In our
      experience, the rate of growth of tumour is very slow and a wait and watch policy
      can he adopted for very small tumours and those that are incompletely resected.

PMID- 23119970
TI  - Periosteo-Temporofascial flap for cavity obliteration - first Indian study.
AB  - Healing of the mastoid cavtiycompletely is the desired result after a mastoid
      surgery. Even after the Sade's principles' of the complete disease clearance,
      adequate lowering of the facial ridge, good meatoplasty and closure of the
      perforation of the tympanic membrane are fallowed, the complete healing of tike
      mastoid cavity is sometimes net the end result. According to various surgeons,
      the incidence of discharging mastoid cavity after a open cavity mastoid surgery
      is between /0-60%-H The usual techniques of obliteration of the mastoid cavity to
      decrease the size of the mastoid cavity, unusually has good healing results due
      to good vascularity. The failure ta the early detectmn 0/disease recurrence and
      risk of sudden appearance of intra-cranial complications are the most important
      disadvantages of the technique. We undertook a study in SO randomly chosen
      patients of Unsafe CSOM. Twenty five underwent obliteration of the mastoid cavity
      with Periosteo-Temporofascial flap, which is based on branches of posterior
      auricular artery and rest twenty five underwent non-obliteration of the mastoid
      cavity. Tfie results between the two groups were compared in terms of healing of
      the mastoid cavity and hearing gain after operation. Very good results in terms
      of healing of the cavity were seen after obliteration surgery. The rate of
      healing of the cavity was much faster after obliteration. The additional
      advantage with the flap is the see-through character of the cavity lining, which
      would lead to early detection of the disease recurrence. No significant increase
      in the hearing was seen in the obliterated patients as compared to non
      obliterated cases.

PMID- 23119971
TI  - Study of anomalies of thyroglossal tract.

PMID- 23119972
TI  - Pattern of drug utilization in acute tonsillitis in a teaching hospital in Nepal.
AB  - OBJECTIVE: A prospective study was undertaken to find out the baseline data on
      prescribing patten of drugs in acute tonsillitis. METHODS: Prescriptions far
      acute tonsillitis were collected outside the ENT-OPD over a period of 6 months
      and were analyzed. RESULTS: The average number of drugs per prescription was
      3.24. Ninety five percent of the prescriptions contained antimicrobial agents
      (AMA with an average of 1.03 AMAs per prescription. AMA was the most commonly
      prescribed (31.81%) group of drugs followed by analgesics and antipyretics
      (20.70%). Amoxicillin (38.80%) and azithromycin (20.63%) were the most commonly
      prescribed AMAs. Erythromyein was prescribed in 11(6.73) patients while
      penicillin was not at all prescribed. Culture and sensitivity test was advised
      only in 14.75% of cases. Cough expectorants were the most commonly used fixed
      dose combination. Of the total drugs used, 96.9% were prescribed by brand names.
      The duration of therapy was not mentioned for 35.60% of the drugs prescribed. the
      iatyprtyriate and over use off antimicrobil agents make treatment east effective.

PMID- 23119973
TI  - Thyroplasty type I - Apollo hospital experience, with a brief review of
      literature.
AB  - Thyraphtsty Type I in Phonosurgery is one of the techniques first practised by
      Prof. Isshiki, a pioneer in this field. The technique that we adopted is a tittle
      different from his technique, which is highlighted in a series of six cases, done
      at Apollo Hospitals, Chennai from December 1997 to April 2001. The postoperative
      results were quite good and the patients could phonate without any effort
      Patients followed up for one year showed no deterioration in phonation and they
      are back in their profession. A brief review of literature is documented.

PMID- 23119974
TI  - Phonomicrosurgery for benign vocal Fold lesions - our experience.
AB  - Benign lesions of glottis creates stiffness of the vocal fold and inefficient
      glottal valve, aerodynamically effecting the vocal quality by preventing smooth
      vocal edge closure. Introduction of phonomicrosurgical techniques based on Hirano
      's principle of vocal fold epithelium have revolutionized results of voice
      surgery. Our experience in the management of benign vocal fold lesions by
      phonomicrosurgical techniques with pre and post operative stroboscopic,
      perceptual and computerized acoustic voice analysis is described.

PMID- 23119975
TI  - Superior based turnover pharyngoplasty flap for velopharyngeal insufficiency -
      our experience.

PMID- 23119976
TI  - Van Der Hoeve-De Kleiyn'S syndrome as a rare cause of hearing loss - two case
      reports.
AB  - It is relatively rare, dominant form of syndrome characterized by combination of
      blue sclerae brittle banes and Hearing loss. One of the conditions may be absent.
      Two cases, one 22 year old mtde with UltUtgray selrae md the other a 25 year old
      female with blue sclerae presented to us with hearing loss. Family history of
      hearing toss and blue sclerae were positive.

PMID- 23119977
TI  - Neurilemmoma of tongue.
AB  - Neurilemmoma is usually soimry, benign tumour derived from schwan cells of the
      Sheaths of peripheral cranial or autonomie nerves. In thehead and neck region it
      occurs most commonly in association with acoustic nerve within the skuil and is
      rely fottnd in the oral cavity (1,2). We report here two cases of the iongue
      diagnosed on histopathohgy.

PMID- 23119978
TI  - Penetrating oesophageal foreign body.
AB  - The behaviour of impacted foreign bodies in the Oesophagus is very often
      unpredictable. Though penetration with subsequent migration into the thyroid
      gland is an extremely rare event, with only occasional reports in medical
      literature, this possibility should always be borne in mind because of the
      likelihood of serious complications like aorto-oesophageal fistula, subctavian
      oesophageal fistula and retropharyngeal abscess. The usual presenting features
      are persistent pain and foreign body sensation with no evidence of the foreign
      body on converntional oesophagoscopic examination.

PMID- 23119979
TI  - Unusual presentation of a giant glomus tumor.
AB  - Giant glomus tumors pose a challenge to the Otologist by virtue of their location
      and vascularity. A vast majority of them present with tinnitus, conductive
      hearing loss and cranial nerve palsies. We report the case of a 16-year-old male
      patient who presented with sudden right-sided sensorineural hearing loss. This is
      an unusual presentation of a giant glomus tumor. We present the clinical features
      and management of this unusual case.

PMID- 23119980
TI  - A case of large dentigerous cyst containing canine tooth in the maxillary antrum.
AB  - A ease of large dentigeram cyst containing a canine tooth in the maxillary antrum
      is presented. This case is of interest because of its extension up to the skull
      base and presence of canine tooth in the cyst. Excision of cyst containing the
      eclopic tooth was made.

PMID- 23119981
TI  - Bilateral hamartoma of tonsils bearing ectopic teeth: a case report.
AB  - Ectopic teeth presenting in bath the tonsils with hatnartomatous lesion has not
      been reported earlier. We present here a case of benign hamartoma of both the
      tonsils bearing 7 teeth in a 13 year old girl and also discuss about unusual
      Ectopic sites of tooth eruption as well as benign lesions of tonsil.

PMID- 23119982
TI  - Primary mucoepidermoid tumor of the middle ear and mastoid.
AB  - Mucoepidermoid tumors are salivary gland neoplasms located mainly in the parotid
      gland. We present an unusual case of such a tumor arising from the middle ear and
      mastoid cavity successfully treated by surgery and post-operative radiotherapy.

PMID- 23119983
TI  - Fibrous variant of rhinophyma.
AB  - Rhinophyma is a rare disease which causes disfiguring soft tissue hypertrophy of
      the nose. The fibrous variant of rhinophyma is still rare which mimics fibrous
      papule of nose and lupus pernio. We report an unusual fibrous variant which was
      surgically managed with the good results. The use of scalpel for sculpting and
      the use of split thickness skin graft is being highlighted.

PMID- 23119984
TI  - Mucormycosis.
AB  - A rare case of mucormycosis in a 58 years old healthy house-wife is reported
      which occurred without any predisposing factors like immuno-suppresion. Etiology,
      clinical features and treatment is outlined with the caution that the most
      effective drug i.e. amphotericin B may have very serious side effects as in this
      case. The disease is acutely fatal and treatment has potential hazards which may
      prove fatal. However, if the disease entity is kept in mind, with early diagnosis
      and treatment, the outcome would be quite favourable.

PMID- 23119985
TI  - Telemedice in otolaryngology (An Indian Perspective).
AB  - Telemedicine is an upcoming concept in the modem world, It needs to be inculcated
      to improve the coordination amongst the health care providers in order, not only
      to update themselves but also to provide a coordinated approach far eatering
      masses in a developing country The various advantages and drawbacks are
      highlighted, and stress is made on starting a remote method of tetecommunication
      amongst us.

PMID- 23119987
TI  - Minimally invasive technique (mit) in endoscopic sinus surgery.

PMID- 23119986
TI  - The role of propofol as a general anaesthetic agent in surgery for sinonasal
      diseases.
AB  - Propofol is known to he a better drug when used for induction of general
      anaesthesia. But when it is used for induction as well as maintenance of general
      anaesthesia in the surgery for sinonasal diseases, it significantly reduces the
      blood loss thereby improving the risibility of the endonasal structures and
      minimises the chance of complications related to endoseopic sinus surgery.

PMID- 23119988
TI  - Juvenile nasopharyngeal angiofibroma-three years experience.
AB  - Juvenile nasopharyngeal angiofibroma is a rare, highly vascular, histologically
      benign but locally invasive tumour, affecting almost exclusively adolescent
      males. This is a prospective study of 37 patients with juvenile nasopharyngeal
      angiofibroma treated during 3 years in our institution. The various pharyngeal
      and extrapharyngeal presentation staging and proper surgical approaches as per
      extensions are discussed here with reference to past reports.

PMID- 23119989
TI  - Cervicopectoral rotation flap for primary closure of lateral face and neck
      defects.
AB  - OBJECTIVE: To recount our experience with the cervicopecloral flap (clavipfcmral
      flap, herein after referred to as CVF) fur reconstruction of large lateral
      cervicofacial defects in fifteen patients, which has been underutilized and has
      not received due recognition in world literature pertaining to reconstructive
      surgery. STUDY DESIGN: Retrospective case review SETTING: Tertiary care regional
      cancer referral center. PATIENTS: Those with lateral cervicofacial defects
      resulting from extirpative cancer surgical resection. RESULTS: A 100%
      &#x2018;take rate&#x2019; was observed at the primary defect. In 7% there was
      full thickness, distal loss that was successfully managed by split thickness skin
      grafting. Three cases (20%) shaved superficial epidermolysis, which healed by
      full epithelization within three weeks. CONCLUSION: This flap provides
      satisfactory primary closure of surface defects that do not extend beyond an
      arbitrary line extending from the angle of mouth to tragus and posteriorly beyond
      the mastoid.

PMID- 23119990
TI  - Office based trans nasal esophagoscopy, and its role.
AB  - Trans Nasal Esophagoscopy (TME) - a new concept to visualize the esophagus in
      office practice has obviated the conventional rigid esophagoscope, which is a
      cumbersome, time consuming procedure and sometimes associated with complications
      like perforation. Many surgeons in the West using flexible endoscope after air
      insufflation have tried this procedure. We fabricated a new gadget far the
      purpose of air insufflation in collaboration with the department of biomedical
      engineering, Apollo hospitals, Chennai which substitute oxygen insufflation
      through central supply or through the flow meter connected to an O(2) cylinder.
      In this article we have discussed various uses of the procedure in diagnosis A
      therapeutic application in an E.N.T office practice and also the unique technique
      of air insufflation with the new gadget.

PMID- 23119991
TI  - Clinicopathological study of tumous of hypopharynx.
AB  - Thirty cases of tumors of hypopharyiix were admitted in EST department ofRujendra
      Hospital, Patiala for ciinicopathological study. Peak age incidence of tumours
      was seen in 6th decade of Life. Males were affected more than females (23:7),
      Alcohul consumption, smoking and poor orodental hygiene were important
      predisposing factors responsible for the disease. Maximum number of cases the
      growth was seen in pyrifarm fossa (80%). Dysphagia, neck mass and throat pain
      were commonest symptoms. AU cases were found to be Mstologicalty squamous cell
      carcinoma. Most of the patients presented in advanced stage with cervical
      lymphnode metastasis in 60% of cases.

PMID- 23119992
TI  - Rhinolith.

PMID- 23119993
TI  - Incidence evaluation of snhl in high risk neonates.
AB  - OBJECTIVE: to evaluate hearing in high-risk neonates to find the incidence of
      congenital and early acquired sensory-neural hearing loss. STUDY DESIGN AND
      SETTING: The study was designed as a consecutive cases, hospital based study in a
      tertiary care hospital. PATIENTS: The subjects were 70 normal born neonates and
      70 high-risk neonates. The 70 neonates with various high risks included in the
      study had family history of deafness, prematurity, IUGR, asphyxia, perinatal
      infections, hyperbilirubinemia, neonatal sepsis, meningitis, ototoxicity and
      fetal malformations. INTERVENTIONS: The study was conducted over a period of two
      years from Sep 2000 to Aug 2002. BERA using Octavus neuro-otological computer and
      a main unit BERA module with integrated pre-amplifier was performed within first
      28 days of life and at 6 months follow up. RESULTS: 44 out of 140 neonates showed
      abnormalities on initial BERA testing. 28 ears out of 67 ears (44 neonates) had
      losses confirmed at repeat BERA. Wave V was considered to determine the threshold
      of hearing and was found to be consistently present in neonates and also the wave
      . Hyperbilirubinemia (18 cases) and prematurity (29 cases) were the most commonly
      observed. The cases of Hyperbilirubinemia showed raised thresholds, absolute
      latencies and Wave 1 abnormalities (suggesting affection of eighth nerve). In the
      cases of Prematurity, 8 ears showed raised threshold at follow up. Asphyxia was
      found in 5 cases and is known to affect the auditory nerve. Family history of
      deafness found in 3 cases showed X-linked inheritance in one case and autosomal
      recessive inheritance in the others. Perinatal Rubella was observed in two cases,
      which showed hearing loss. Congenital malformations were seen in 7 cases
      (Waardenberg, Downs, Hydrocephalus and T-O Fistula). Neonatal Sepsis was observed
      in 3 cases and is known to affect the eighth nerve. IUGR was observed in 3 cases,
      two had normal hearing while one had no waveforms. CONCLUSION: BERA should be
      used as a screening tool to test the auditory function in all high-risk neonates.

PMID- 23119994
TI  - Primary laryngopharyngeal reconstruction using pectoralis major myocutaneous
      flaps - Our experience.
AB  - Twenty-one eases of laryngectomy/laryngopharyngectomy that required primary
      reconstruction with P. M. M. C flaps at the Division of Surgical Oncology,
      Regional Cancer Centre, Triyandrum were studied retrospectively from July 1995 to
      December 2090 and compared with the in cases where primary closure of the
      neopharynx was done.Four of the 21 cases developed post operative
      pharyngocutaneous fistulae PCF(I9%) which healed Complefely within an average
      period of I week compared to 4 PCFs (40%) after primary closure. (n=10), where
      the average healing time was 12.5 days, with I recurrence. The average duration
      of Onset of fistula was relatively earlier in cases that required primary closure
      (II days) compared to those cases where P. M. M. C flap was used for
      reconstruction (12.5 days). All complications were Wound related and managed
      conservatively.

PMID- 23119995
TI  - Endoscopic excision of Juvenile nasopharyngeal angiofibroma - A comprehensive
      approach.
AB  - OBJECTIVE: Endoscopie excision of Juvenile Nasopharyngeal Angiofibroma (JNA) was
      carried out with (he objective of minimizing blood loss and attempting a complete
      excision of the tumor under direct vision with the help of Hopkins telescopes.
      STUDY DESIGN: A prospective 4 year study of 23 cases of JNA treated by endoscopie
      excision is presented. Of these, 18 were treated by endoscopie excision alone.
      The remaining 5 were treated with a two staged approach either by mid-facial
      degloving followed by endoscopy or by 2 endoscopie procedures. RESULTS: The tumor
      was excised completely in 17 out of the total 18 cases that were treated
      exclusively by endoscopy. One case has shown a recurrence. The 5 cases treated by
      the staged approach represented very large tumours or tumours with intra-cranial
      extensions. In I of these cases, inoperable tumor remnant engulfing the internal
      carotid artery was treated by radiotherapy post-operatively. CONCLUSION: With
      successful excision of JNA in all but one case, we could reasonably conclude,
      that endoscopie excision of JNA could become a safer and a more precise
      alternative to open surgery provided it is practiced judiciously by surgeons who
      have considerable experience in endoscopie surgery and the necessary backup to
      convert to open surgery should the need arise.

PMID- 23119996
TI  - Peritonsillolith.
AB  - PeriionsUiolith appears: to be very rare entity. Two cases eflithiash in
      periionsillar region with peritomillar abscess have been reported. In my case
      PeritoHsitlolitk presented as soft palate muss une was not associated with any
      acute or chronic tonsiUar infection, therefore this ease is being presented.

PMID- 23119997
TI  - Nasopharyngeal angiofibroma with cavernous sinus involvement - An unusual
      presentation.
AB  - Juvenile nasopharyngeal angiofibrama (JNA) is a benign vascular tumour which is
      locally aggressive and occasionally extends intracranially. It occurs mainly in
      adolescent males. We report an interesting case of a targe JNA with intracranial
      extention encroaching on the cavernous sinus which we treated surgically by the
      conventional lateral rhinotomy and transpalatal approach.

PMID- 23119998
TI  - Unusual foreign body in the trachea.
AB  - A great variety of foreign bodies in the traeheohr onvhial tree have been
      reported, but presence of fractured tracheostomy tube as foreign body is ran1.
      Usually fractured pieces of outer tube are found in the bronchus or trachea near
      the carina, but occurence of inner tube in the upper part of the trachea is rare2
      and one such case is presented here.

PMID- 23119999
TI  - Presentation and management of deep neck space abscess.
AB  - OBJECTIVE: To study the presentation, etiology, microbiology and morbidity of
      deep neck space infections. STUDY DESIGN: Retrospective study Methods: 29
      patients admitted in Kasturba Medical College Hospital, Mangulore, India between
      January 1997 and December 2002 with deep neck space infections.,were included in
      the study. REMITS: The most common space involved was the parapharyngeul space.
      No specific etiology was determined in .38%; an odontogenic cause was discovered
      in 28% of the patients; tonsillar/pharyngeal infections in 24% of patients and
      foreign body impaction in 7% of cases. The main morbidity was due to
      mediastinitis (5 patients). I patient succumbed to the disease. Mixed flora with
      aerobic and anaerobic infections was identified in most of the cases.

PMID- 23120000
TI  - Cytodiagnosis of submandibular sialadenitis with crystalloids mimicking
      metastasis.
AB  - Sialomrgaly of suhmandibultir gland, whether inflammatory or neoplastic can be
      clinically mistaken for lymphoid metastasis especially when encountered in an
      elderly patient. Other than the neoptastic lesions and usual inflammatory lesions
      rarely amylase crystalloids can evoke a granulomatous response and can result in
      sialomegaly. We report an interesting case which presented as a submandibular
      swelling and was clinically diagnosed as metastasis where the diagnosis of
      granulomatous response to crystalloids was made at FNAC. The aim of this report
      is to bring an awareness of the existence of such lesions and to highlight the
      role of FNAC in diagnosis of such lesions in order to avoid unnecessary
      surgeries.

PMID- 23120001
TI  - Solitary malignant schwanoma of para pharyngeal space-a case report and review of
      literature.
AB  - Malignnant Schwannom is an aggressive tissue tumor that is more cnmitutnh found m
      assoiiatiun with Ion Recklinghausens disease. The solitary tumors although rarer
      have a better prognosis when compared to those associated witk tan
      Recklinghausens disease. Parupharyngeui tumors are rare and a majority af these
      are benign salivary or neurogenie tumors, A malignant Schwannoma at this site is
      very infrequent with only four earn reported so far. The tase of a 16 year old
      girl with a parapharynccal malignant Schwnnaomu is presented Jor its rarity and
      our experience in dealing with it. .A combined modallty oftretument with
      surttery, radiotherapy and chemotherapy Was used. Pertinent literature h
      revlewed.

PMID- 23120002
TI  - Pleomorphic adenoma of the nasal septum.
AB  - Despite the common occurrence of pleomorphic adenoma of major salivary glands,
      intranasal pleomorphic adenoma are rare. We present a ease of pleomorphic adenoma
      of the nasal septum along with a brief review of literature. The histological
      nature of this lesion in comparison to other salivary gland tumours and the
      importance of an accurate diagnosis has been stressed.

PMID- 23120003
TI  - Nasal tooth.

PMID- 23120004
TI  - Asymptomatic impacted foreign body of larynx.
AB  - A rare case of asymptomatic impacted foreign body coin of larynx is repearted.

PMID- 23120005
TI  - Oesophageal foreign body in four month old infant.
AB  - A 4 month old male infant was brought with only strong suspicion of foreign body
      ingestion without any symptomatology. X-ray examination revealed foreign body at
      cricopharyngeus, which was managed successfully emphasizing the fact that a
      strong suspicion and relevant radiography is the key to early and successful
      management.

PMID- 23120006
TI  - Uncommon complication of quinsy.
AB  - rare case of &#x201C;quinsy with uncommon complication&#x201D; and its manaement
      with review of literature is reported. Quinsy as a complication of acute or
      chronic Tonsillitis and Dental Infection is still seen at regular frequency
      inspite of modern antibiotics. This case inspite of having an early and proper
      incision and drainage ended up having retro and para-pharyngeal abscess which
      tracked down leading to Mediastinitis and Empyetna Chest. Early Inter-Costal
      drainage prevented fatality and helped in rapid recovery.

PMID- 23120007
TI  - Orbital pneumatocele.
AB  - Air in the orbit is usually a result of trauma to the orbit but here we report a
      case of spontaneously occurring orbital Pneumatocele which followed about of
      sneezing and clearing of nose. The rare site communication at frontoethmoid
      junction is highlighted with relevant review of literature.

PMID- 23120008
TI  - Papillary thyroid carcinoma in a thyroglossal cyst.
AB  - The incidence of Papillary Thyroid Carcinoma in a Thyroglossal Cyst is rare. Only
      about 160 cases have been reported in the last 85 years. We report a case of
      Thyroglossal Cyst who underwent Sistrunk &#x2019;s Operation. The Cyst was
      reported to contain a focus of papillary thyroid carcinoma. In the absence of
      metastases in thyroid gland and neck nodes, only thyroid suppression with
      Thyroxine was given. After I year of follow-up there are no metastases. The
      importance of Sistrunk&#x2019;s operation lies not only in complete removal of
      Thyroglossal Cyst but also in management of small foci of Papillary thyroid
      Carcinoma.

PMID- 23120009
TI  - An unique case of organic foreign body (bone) in the hard palate.
AB  - A unique report of impacted organic foreign body (animal bone) in the hard palate
      is presented. A patient with vague palatal discomfort for two years reported to
      the ENT OPD, work-up revealed the above foreign body, subsequently proven to be
      bone by histology.

PMID- 23120010
TI  - Verrucous carcinoma of the maxillary antrum.
AB  - Verrucous carcinoma is a well-differentiated variant of squumous cell carcinoma.
      In this article, we present a patient of verrucous carcinoma of the maxillary
      annum. There are only 6 reported cases of verrucous carcinoma of the maxillary
      antrum. Ours is the 7th case. We, here, would like to highlight that our case had
      a different clinical presentation from the previously reported cases.

PMID- 23120011
TI  - The eustachian tube, the otologist's engima.

PMID- 23120012
TI  - Incidence of lymphomas in head and neck region.
AB  - In the present study 109 cases of Heck swellings were subjectedto F.V.A.C.
      examination. H vases teere found to he positive for lymphomas with 62.5% eases
      presenting as cervical lymphade.nopathy. Median age of presentation tints 48
      years with preponderance of femulr patients. 57.2% of the patients presented in
      stage I of the disease.

PMID- 23120013
TI  - Laryngeal melanosis.
AB  - We describ a case iaryngcul melanosis in a 62 year old male. the pigmentation was
      visible on gross examination during laryngoscopy ana histologicatly a single foci
      showing changes of carcinoma in situ was identified. The biopsy tissue, however
      did not reveal any frank changes of malignancy.

PMID- 23120014
TI  - Structured training in otorhinolaryngology- head and neck surgery.
AB  - Although mut ENT departments in India are now departments of OtolaryHifniogy-Head
      and Neck surgery there is no uniform structured training programme to ensure that
      the postgraduates will receive a thorough grounding in the various subspecialties
      that make up modern otolaryngology. .4 model programme is presented which may
      serve as a basis for future discussion.

PMID- 23120015
TI  - Management of laryngo-tracheal stenosis by shiann - yann lee technique.
AB  - Laryngotracheal stenosis is a partial or complete cicatricial narrowing of
      endolarynx or trachea. It has became mare common for two reasons; first,
      increasing prolonged endotracheal intubations for mechanical ventilation,
      secondly, increase in trauma to anterior part of neck due to vehicular accidents.
      We present our study of 30 cases of laryngotracheal stenosis operated by 'Shiann
      Yann Lee's technique with T tube stealing from January 1997 to January 2003. In
      our experience this is relatively simple technique with higher success rate of
      decannulation.

PMID- 23120016
TI  - Interposition arthroplasty in temporomandibular joint ankylosis.
AB  - We report a series of 60 cases of post- traumatic temporomandibular joint
      ankylosis that were treated at our unit from 1992 to 2002 by temporalis fascia
      flap interposition arthopiasty. Majority of these patients (21 patients, 35%)
      were in the age group of 15-20 years, with 39 males (65%) and 21 females (35%).
      The duration of ankylosis varied from 6 months to more than 4 years with 32
      patients (54.32%) having a duration of 6 months to 2 years. 44 patients (73.33%)
      had unilateral white 16 patients (26.67%) had bilateral involvement of
      temporomandibular joint. Pedicled temporalise fascia axial flap based on
      superficial temporal artery was used for interpositional arthopiasty. The
      advantage is that it is available at the operative site, easy to raise, well
      vascularized, reliable and with better long term results. Adequate mouth opening
      was achieved in all cases and a long follow up, of up to 10 years for the earlier
      operated cases, showed no recurrence of ankylosis in any of the patients.

PMID- 23120017
TI  - A comparative study of radiological and antroscopic findings in the lesions of
      maxillary sinus.
AB  - This study was done to assess the relevance of radiological examination in
      comparision to endoscopic examination in diagonis of maxillary sinus lesions. X
      ray para nasal sinuses was done in sixty six patients and CT scan in 18 patients.
      Antroscopy was performed in all the cases (133 sinuses). The correlation between
      X -ray examination and antroscopy was found to be poor i.e. 52.4% with 95%
      confidence interval of 39.5-65.5% while that between CT scanning and antroscopy
      was good i.e. 90% with a 95.5 confidence interval of 77.8%-100%. The difference
      between the two correlations with highly significant satistically (p<0.001). The
      findings are discussed.

PMID- 23120018
TI  - Sore throat - a review of presentation and etiology.
AB  - A commonly encountered complaint in clinical practice is that of a sore throat.
      However, confusion prevails in the minds of the treating specialists as to what
      treatment protocol should be followed and how to differentiate it from
      tonsilliti. It was with a view to clarifying this issue that a prospective study
      was undertaken on 50 patients with the presenting complaint of a sore throat, of
      which 20 received medical treatment and 30 underwent a tonsillectomy. The
      preoperative throat swabs versus fine needle aspiration cultures and core
      cultures were also analyzed us were some predisposing factors. Available
      literature was reviewed and compared with findings of the current study. On the
      bash of this, a protocol for treatment was developed including antibiotic
      preference and best method of microbiological isolation of offending organisms.

PMID- 23120019
TI  - Efficacy of conservative treatment modalities used in epistaxis.
AB  - OBJECTIVE: To assess the efficacy of conservative modalities in the management of
      epistaxis. STUDY DESIGN: Prospective case studies. SETTING: Rural medical college
      hospital. PATIENTS: Indoor and outdoor patients with epistaxis.  LNTERVENTION:
      Conservative(non surgical) management techniques in epistaxis. RESULTS: Chemical
      cauterization was successful in 72.07% cases, anterior nasal packing in 84.5% and
      posterior nasal packing in 95.6% cases. CONCLUSION: Out of 300 cases of epistaxis
      included in the study (except for one case that required internal maxillary
      artery ligation). all cases were treated successfully with conservative treatment
      alongwith treating the underlying pathology causing epistaxis.

PMID- 23120020
TI  - Inferior turbinectomy for nasal obstruction review of 75 cases.
AB  - 98% of the patients had improved airway after surgery.All the patients with
      hyposmia had increased sensitivity to smell following surgery.80% of the patients
      with asthma and hypertrophied inferior turbinates benefited considerably with
      surgery as they had marked reduction in the frequency of asthmatic attack.In our
      study no cases of ozaena had been reported.There were no complications except for
      3% of patients with epistaxis and synechiae.Patients with allergic symptoms had
      significant reduction in their sneezing attacks.8% of the patients reported mild
      dryness of the nasal cavity after surgery.8% of the patients also noticed not
      much improvement in their nasal discharge after surgery.

PMID- 23120021
TI  - Nasal glioma- a diagnostic challenge.
AB  - In this unusual case there was a difficulty in diagnosis on the basis of
      histopathological reporting. On the grounds of clinical suspiscion one has to try
      to find out the proper diagnosis by advanced diagnostic methods like
      immunohistochemistry.

PMID- 23120022
TI  - A safe and reliable technique in the management of pseudocyst.
AB  - Pseudocyst is a benign asymptomatic swelling, which develops in the lateral and
      anterior aspect of the pinna-scaphoid and triangular fossa. Usually occurs due to
      defect in the auricular embryogenesis. The paper describes a simple and safe
      technique carried out in 27 cases. The cartilage is exposed by making a linear
      incision in the posterior aspect of the pinna and a rectangular piece of
      cartilage if excised. The wound is then closed with drain in-situ. The patients
      were monitored for a period of 2 months, during which no recurrence or alteration
      in shape was noted. Hence, this procedure can replace other modes of treatment.

PMID- 23120023
TI  - Salivary gland tumors - our experience.
AB  - Salivary gland neoplasms represent the most complex and diverse group of tumors
      encountered by the head and neck oncologist. Their diagnosis and management is
      complicated by their relative infrequency (1% of head and neck tumors)1, the
      limited amount of pre-treatment information available and the wide range of
      biologic behavior seen with the different pathologic lesion. Approximately 80% of
      salivary gland tumors are found in the parotid gland, 10 to 15% in the
      submandibular gland and 5 to 10% in the minor salivary glands. This retrospective
      study was conducted at government Medical college & Hospital, Chandigarh
      including 36 patients treated between January 1997 to June 2001 with the aim to
      contribute to the discussion about the best way to treat salivary gland neoplasms
      by analyzing data of patients treated in our hospital.

PMID- 23120024
TI  - Unilateral progressive proptosis in neonate.
AB  - Orbital teratomas are congenital germ cell tumors that present at birth or within
      the first few months of life with unilateral proptosis. Primary orbital teratomas
      produce diffuse enlargement of the orbit. Orbital teratoma contains a wide
      diversity of tissues ranging from undifferentiated mass of tissue to a fully
      differentiated fetus in fetus. The tumor components are derived from two or more
      germinal layers. Most teratomas are cytnlogically benign, having both cystic and
      solid areas and on occasions may undergo a malignant change. Most patients in the
      past have been treated by orbital exenteration. We report a case of orbital
      teratoma that rapidly progressed over a course of days.

PMID- 23120025
TI  - Ossifying fibroma of nose in a two year old child.
AB  - We report a cast of ossifying fibroma of the nose, arising from the bony septum
      and extending into the nasophaynx in a 2 yrs. old child presenting with features
      of obstructed nose.

PMID- 23120026
TI  - Neurofibroma of paranasal sinuses - a case report.
AB  - Primary neurogenic tumors in nose and paranasal sinuses are unusual entities. The
      majority of the reported cases have dealt with neurilemmomas and isolated
      neurofibromas are extremely rare. Here a case of neurofibroma of the paranasal
      sinuses is described.

PMID- 23120027
TI  - Kimura's disease.
AB  - A 12 year old child developed primary unilateral cervical mass. Routine
      investigations were inconclusive except cosinophibilia. Excision biopsy revealed
      the diagonisis as Kimura's Disease. Retrospective investigations confirmed it.
      This disease should be suspected when a patient presents with tetrad of painless
      unilateral cervical lymphodenopathy. Eosinophilia, Hyperimmunoglobulimemia
      (??/gE) & Positive Candida Specific Antibodies. A flow chart has been drawn to
      treat this condition after review of literature.

PMID- 23120028
TI  - Laser in treatment of laryngeal amyloidosis.
AB  - Amayloidosis is the extracellular deposition of the fibrinous protein amyloid in
      one or more body sites. Amyloidosis may broadly be classifed as either primary or
      secondary. Primary amyloidosis is idiopathic (56 %), whereas the secondary form
      is associated with a chronic inflammatory or infectious process (5%). Amyloidosis
      is also related to multiple myeloma (26%), senescence (5%) and where tumor like
      deposits occur in isolated organ without systemic involvement (8%). Laryngeal
      amyloidosis is a rare disease. Surgery has been the mainstay of treatment either
      endoscopicalfy or by an external neck approach. One case of laryngeal
      amyloidosis, treated with endolaryngeal microsurgery and carbon dioxide laser is
      presented with a follow up of 8 years.

PMID- 23120029
TI  - Gun shot wound neck.
AB  - All penetrating neck wounds are potentially very dangerous and require emergency
      treatment. The choice of treatment for the stable patient remains controversial,
      a number of studies encouraging mandatory surgical exploration and a similar
      number encourage selective surgical exploration. Knowledge of the physical
      properties of the penetrating object or weapon can help to determine a treatment
      plan and predict the risk of injury- All tracheal and esophageal injuries with
      structural damage should be repaired primarily. A case of Gun Shot Wound Neck was
      air evacuated to Army Hospital R & R Delhi Cantt in a tracheostomised state.
      Patient was evaluated in detail, he had trachea esophageal fistula. The
      management of this case is discussed along with principles of management of war
      injuries.

PMID- 23120030
TI  - Nasal encephalocoele -an atypical case.
AB  - Nasal encephalocoele present at birth as a characteristic swelling over the nose
      and widening of intracanthal distance. Atypical nasal encephalocoeles are usually
      missed at birth due to absence of any external swelling and they present with
      diagnostic difficulties. These are very rare and present with only an intranasal
      mass. We report a case of an atypical nasal encephalocnele in a 8 year old boy
      who presented with a unilateral intranasal mass and cerebrospinal fluid
      rhinorrhoea.

PMID- 23120031
TI  - Verrucous carcinoma of larynx.
AB  - A 55 years male presented with hoarsness of voice (4 months), cough (1 month),
      difficulty in breathing (15 days). Patient underwent an emergency tracneostomy
      and further workup proved it to be a case of verrucous carcinoma of larynx.
      Patient was treated surgically with satisfactory result.

PMID- 23120032
TI  - Tuberculosis of parotid gland - a rare clinical entity.
AB  - Tuberculosis of parotid gland is rare. In our country with high incidence of
      tuberculosis we should think about it in differential diagnosis of any parotid
      swelling with multiple fistulae because pre-operative diagnosis can help to avoid
      unnecessary parotidectomy.

PMID- 23120033
TI  - Malignant melanoma of the nose.
AB  - Malignant Melanoma of the nose is a rare neoplasm, with primary mucosal melanoma
      being more aggressive than its cutaneous counterpart (Land,1982). The
      presentation is often not as dramatic as compared to its progression. While
      cutaneous melanomas typically present with obvious and consistent features,
      melanomas of the mucosal form are often diagonised late due to their hidden
      location and relatively non-specific features. This tumour can metasiasise by
      lymphasies or bloodsream. Moreover the tumour is often quite resistent to
      complete cure especially due to reccurence and metastotis. We wish to empahsize
      that early diagonisis with a high index of suspicion is essential for the
      management of this condition, by means of two case reports of patients who
      attended the ENT clinic at Southend Hospital, UK, both of whom were being treated
      for nasal polyposis in whom the diagonisis susbsequently turned out to be
      malignant melanoma.

PMID- 23120034
TI  - Proliferative fascitis of nose.
AB  - Rapidly growing soft- tissue lesions in the oral and maxillofacial region can
      represent a variety of diagnoses involving radically different treatment
      modalities. Accurate diagnosis is important to avoid unnecessary and often
      mutilating surgery. Nodular fascitis is a rapidly proliferating fibroblastic
      lesion that presents as a tumour- like mass. Up to 20% of cases occur in the head
      and neck region.

PMID- 23120035
TI  - Unusual experience in osmf.

PMID- 23120036
TI  - Blunt dissection to bipolar forcep tonsillectomy- a comparision.
AB  - Bipolar diathermy forcep or scissors dissection is safe and trusted and
      established procedure now and have an edge over blunt dissection. If monopolar
      diathermy is used, high voltage current should be used for dissection with fine
      point and if bipolar is used, low voltage current should be used, diathermy tip
      should be cleaned with wet gauge piece, fossae should be packed with wet gauge
      only, minimum required current and only coagulation should be attempted, avoid
      injury to surrounding tissue resulting to minimum sloughing. Avoiding thermal
      injury to surrounding tissues leads to lesser post operative pain. Results
      depends upon the precision of technique and expertise developed over a time
      especially coagulating the vessel during dissection before spurt. Considering
      cost effectiveness, bipolar diathermy is much economical than ultrasonic and
      laser to provide comparable results in terms of better results, duration of
      surgery, anaesthesia and overall postoperative morbidity.

PMID- 23120037
TI  - Endoscopic pituitary surgery - a. beginner's guide.
AB  - Endonasal endoscopic surgery is now the preferred technique to tackle pituitary
      tumours. Our paper describes the stepwise endoscopic approach for surgeons
      embarking on pituitary surgery. It also highlights the common pitfalls
      encountered during surgery and the ways to avoid them. One must proceed in a
      gradual step- wise manner starting from simple exposure of the sphenoid sinus to
      complete endoscopic tumour removal so us to gain the neurosurgeon's confidence as
      well as develop our own skills, confidence and ability to tackle complications.
      We use the endonasal paraseptal trans- sphenoidal approach. Surgery begins with
      gentle packing between the middle turbinate and septum to expose the anterior
      sphenoid wall and expose the sphenoid astium. The ostitum is then widened
      inferiorly and onto the opposite side to expose both sphenoid sinuses. The inter-
      sphenoid sinus and necessary mucosa is removed to expose the sella. We then use a
      bone flap technique or punches to open the sella. After incising the dura, tumour
      is removed with a suction curette. An endoscope holder facilitates the operation.
      The bone flap is replaced at the end of surgery to reconstruct the sella. This is
      especially important if a CSF leak is present. Nasal packing is usually not
      required.

PMID- 23120038
TI  - Mast cell quantitation in non- neoplastic polypoidal nasal lesions.
AB  - The distribution and abundance of mast cells was studied in 110 nasal non-
      neoplastic polypoidal lesions. In most of the polyps of all kinds, the epithelium
      showed less than 5000 mast cells/mm(1). Out of the 72 so- called "nonallergic
      polyps", 29 (40,3%) showed more than 20,000 mast cells/mm(1) in the subepithelial
      layer, and 30 (41.7%) more than 20,000 mast cells/mm(1) in the deeper areas. Out
      of the 18 so- called "allergic polyps", 8 (44.5%) showed more than 20,000 mast
      cells/ mm(3) in the subepithelial layer, and, 8 (44.5%) more than 20,000 mast
      cells/mm(3) in the deeper areas. Interestingly, mast cells were also seen in very
      high numbers in 33-38% of cases of chronic hypertrophic rhinitis,
      rhinosporidiosis and mucormycosis. There was no correlation between the
      proportion of eosinophils and mast cells in the lesions. We conclude that mast
      cells are not restricted to allergic nasal lesions and the significance of their
      presence in nasal lesions needs to be evaluated.

PMID- 23120039
TI  - Annular ligament reconstruction - a better technique in the surgical treatment of
      stapes fixation.
AB  - Reconstruction of the annular ligament using vein graft at the stapedotomy site
      gives a very good gain at low, frequencies as compared to Stapedotomy without a
      tissue seal It also protects against perilymph leak 1 0 8mm stapedotomy with a 0
      4mm piston with 0 2 mm vein graft interposition is a better technique in the
      surgical treatment of stapes fixation The purpose of the present study is to
      determine the effectiveness of vein graft in sealing the oval window in small
      fenestra stapedotomy for stapedial otoselerosis We performed a prospective
      randomi ed trial in 80 cases of stapedial otoselerosis, 40 with and 40 without
      having a tissue seal at a tertiary referal center Ihere was a good air bone gap
      closure in both the groups There was a better gain in the lower frequencies in
      subjects where the vein graft was used.

PMID- 23120040
TI  - Functional voice disorders and their occurrence in 100 patients of hoarseness as
      seen on fibreoptic laryngoscopy.
AB  - During a six month period, one hundred patients presenting with the primary
      complaint of hoarseness, in the out- patients department of otolaryngology at
      Safdarjung Hospital New Delhi were taken up fot the study Fach patient after
      being subjected to a detailed history- taking and examination, including a
      Fibreoptic Laryngoscopy was then put into one of ten categories on the basis of
      the ultimate diagnosis Functional voice disorders, forming the largest category
      with 51%, included lesions such as vocal nodules and polyps, which are secondary
      to vocal abuse A detailed study of the various types of functional voice
      disorders along with factors such as male female ratio and associated
      contributory factors was done the efficacy of the Fibreoptic laryngoscope as a
      diagnostic tool was also assessed.

PMID- 23120041
TI  - Myocutaneous v/s micro vascular free flaps in oral cavity reconstruction - a
      comparative study.
AB  - Micro vascular free tissue transfer scores over the traditional myocutaneous
      flaps by providing better cosmesis and function. However, the increased operating
      tine and costs and the necessity for two operating teams sometimes, negate these
      advantages and even where this facility is freely available, myoentancous flaps
      continue to be widely used.To determine the ideal choice of reconstruction in
      patients after oral resection, we compared our experience with these two methods
      of reconstruction. Since 1997, when we first started micro vascular
      reconstruction, 17 patients have undergone this procedure for oral
      reconstruction. During this same period, 40 patients had pectoralis major
      myocutaneous flap reconstruction of the oral cavity. These two groups are
      compared with regard to cosmetic and functional results (as measured by patient's
      level of satisfaction) operating time, duration of hospitalization, cost and
      complications. RESULTS: Eightv seven percent of the patients in the micro
      vascular group and 75% in the myocutaneous group were satisfied with the cosmetic
      and functional results. In the microvascular group, average operating time was
      increased by 4 hours; hospitalization by 3 days and average cost of treatment was
      doubled. Flap failures and re-explorations were significantly higher in the micro
      vascular group.Based on these results, we would like to suggest the ideal method
      of reconstruction of the oral cavity in specific subgroups of patients in a
      corporate hospital setting.

PMID- 23120042
TI  - Survival patterns in treated cases of carcinoma larynx in north india - a 10
      years followup study.
AB  - Patients with stage I and II tumors had the best results with radical
      radiotherapy alone 5 years survival for patients with stage I and stage II tumors
      was 90-95% and 75-85% respectively Patients with advanced stage III & IV disease
      were treated Unoperable stage IV cancer patients had poor outcome and received
      only palliative treatment.

PMID- 23120043
TI  - Computed tomography in the evaluation of laryngotracheal stenosis.
AB  - Faryngottacheal trauma of varied etiology may involve the mucosal integrity soft
      tissue structure and cartilagenous, framework at more than one level Computed
      tomography provides crucial and definitive evaluation of the extent of
      cartilagenous and soft tissue injury and status of the taryngeal auway Results of
      this study corroborated well with surgical findings and were helpful in planning
      further management Here in the present series we assess the role of CT in the
      evaluation of 25 patients with laryngotracheal stenosis.

PMID- 23120044
TI  - Anomalies of transverse and sigmoid sinuses associated with contracted jugular
      foramina.
AB  - Variations of the durai venous sinuses may present puzzling diagnostic and
      operative problems in the presence of thrombophlebitis. Such variations in
      sinuses of the posterior cranial fossa are usually associated with contracted
      jugular foramina and a small internal jugular vein. In the present study 214
      sides of the bases of the macerated skulls were examined for the contracted
      jugular foramen and associated anomalies of the durai venous sinuses. In ten
      sides (4.67%) out of these an anomaly of the durai sinus of the posterior cranial
      fossa was found (two of right side and eight of left side). Out of these one case
      of right side was associated with the absence of groove for both transverse and
      sigmoid sinuses. All other cases were associated with the absence of groove for
      transverse sinus alone on the abnormal side. In seven cases out of these the
      jugular foramen was contracted on the abnormal side. The embryological basis and
      clinical significance of the anomalies of transverse and sigmoid sinuses is
      discussed here.

PMID- 23120045
TI  - Interesting case of intraorbital foreign body.
AB  - Penetration of intraorbital foreign bodies into the nose and paranasal sinuses
      although reported in the past are uncommon. Here we present a case of a 26 years
      old male who came to us with a seemingly trivial injury of his right eye due to a
      foreign body. Which on further investigation revealed the major part of a large
      foreign body impacted into the nose and bilateral sinuses, removed successfully.

PMID- 23120046
TI  - Giant fibrolipoma of the oral cavity.
AB  - Firbolipomas are rat e tumors of oral cavity Here, we present a case of giant
      fibrolipoma of the oral cavity.

PMID- 23120047
TI  - Usher' s syndrome.

PMID- 23120048
TI  - Alternating extra medullary plasmacytoma of maxilla.
AB  - Plasmatytomas of maxilla are rare lesions. Alternating plasmacytoma of maxilla is
      still rare. A case of maxillary extra medullary plasmacytoma is reported in a
      patient, who presented with same lesion in the opposite maxillary sinus within
      one year of initial presentation. On review of available literature we could not
      find bilateral medullary plasmacytoma involving both maxilla one after another.

PMID- 23120049
TI  - Anterior jugular phlebectasia.
AB  - Phlebectasia is abnormally dilated vinous channels a rare differential diagnosis
      for an apparent neck swelling A 5 year old male child with neck swelling apparent
      only on crying and speaking presented to us It was a soft cystic swelling The
      diagnosis was confirmed by sonography and angiography Surgical excision was
      carried out without any complication.

PMID- 23120050
TI  - Primary squamous cell carcinoma of the submandibular salivary gland.
AB  - Malignant tumors of the submandibular salivary glands are rare in occurrence,
      among which primary squamous cell carcinoma of the submandibular salivary gland
      is unusual and the documented evidence is 2 to 5% among malignant tumors A case
      of primary squamous cell carcinoma of submandibular salivary gland is being
      presented for its rarity.

PMID- 23120051
TI  - Osteomyelitis of frontal bone.
AB  - A case of Osteomyelitis of the frontal bone with a subperiosteal absces s, an
      extrudural abscess and a frontal sinus fistula is presented here for its rarity.
      A brief review of literature and management of the condition is also discussed.

PMID- 23120052
TI  - Open safety pin in the nasal cavity.
AB  - Foreign bodies in the nasal cavity are common-day occurrences in Otolaryngologic
      practice. But an open safety pin in nose with it' s sharp end directed towards
      roof is a rare incidence, and available literature is silent about this
      presentation; it is probably, the first of it' s kind being reported. Two cases
      of safety pins inside the nasal cavity, one open and the other closed, have been
      presented here with a brief review of literature.

PMID- 23120053
TI  - Neurilemmoma of cervical sympathetic chain.
AB  - Neurilemmoma of the cervical sympathetic chain is a rare nerve tumour. Less than
      40 confirmed cases have been reported in the literature.1 2 Sometimes they can he
      mistaken as carotid body tumour but usual presentation of these lesions is an
      asymptomatic neck mass. Because of the rarity of the tumour we report another
      case of neurilemmoma arising from cervical sympathetic chain in a 19 years old
      male.

PMID- 23120054
TI  - Cyanoacrylate in myringoplasty - an office based procedure.
AB  - Graft failure continues to be a problem for surgery of the perforated eardrum. We
      present our experience of six cases managed using commercially available
      superglue (cyanoacrylate) for myringoplasty. This method is simple, office based,
      less time consuming and cost effective. An insulin syringe was used to deliver
      the glue after a temporalis fascia graft was tucked under the edges of the
      perforation.

PMID- 23120055
TI  - An amazing gunshot injury of the head and neck.
AB  - As the use of firearms has become more prevalent in society, both the number of
      homicidal & suicidal victims has increased Injuries from gunshot wounds, of the
      face and neck vary in extent and significance, forming a spectrum from trivial to
      life-endangering lesions. The face and the neck have many vital structures
      confined to a small area of the body, and hence, it has a greter potential of
      leading to a fatality in the event of trauma. We report a case of a civilian
      homicidal firearm injmy sustained in the head & neck region, with the bullet
      having travelled through the head & neck region without causing any mortality and
      minimal morbidity to the victim.

PMID- 23120056
TI  - Primary rhabdomyosarcoma of the larynx.
AB  - Sarcomas constitute fewer than 1% of the head and neck cancers. They represent
      less than 1% of laryngeal cancers. Primary rhabdomyosarcoma of the larynx is an
      extremely rare malignancy. The available literature on this medical oddity is in
      the form of isolated case reports only. The purpose of this article is to add
      another case of primary rhabdomyosarcoma of a rare site, the larynx, of which
      only 36 cases have so far been reported in the world literature. The present
      patient, an eighteen-year-old boy is only the third case being reported from
      India among all reported cases of rhabdomyosarcoma of the larynx in the world
      literature.

PMID- 23120057
TI  - Midline granuloma in infant.
AB  - Midline Granuloma is a very uncommon disease characterised by localised
      inflamation, destruction and often mutilations of the tissues of the upper
      respiratory tract and face. This unique case is being reported for its rarity
      having the complete destruction of the external nose and part of the upper lip.

PMID- 23120058
TI  - Intra-oral minor salivary duct carcinoma.
AB  - Salivary duct carcinoma (SDC) is a recently described highly malignant tumor,
      seen most commonly in the parotid gland & occurs in the 6th and 7th decade of
      life. Rarely, it occurs in the minor salivary glands. The case is presented
      because of its rare occurrence and unusually presenting as a swelling
      predominantly involving the maxillary bone. The tumor bears histological homology
      with breast carcinoma, prostatic carcinoma and sweat duct carcinoma.

PMID- 23120059
TI  - Haemangiopericytoma of the laryngopharynx.
AB  - Haemangioperitytoma is a potentially malignant tumor of the head neck legion but
      till now none has been reported from the laryngopharynx An interesting case
      involving a young male patient with mild dysphagia and muffling of voice is
      reported The clinical course and management is being discussed.

PMID- 23120060
TI  - Capillary haemangioma of the ethmoid.
AB  - Capillary haemangiomas involving the ethmoid are rare. Two cases are reported
      here. Both the cases presented with recurrent severe ephtaxis. In both the cases
      there were erosion of the middle turbinate. Endoscopic sinus surgery was done.

PMID- 23120061
TI  - Familial clustering of non-medullary thyroid cancer.
AB  - Although genetical inheritance is an well established fact with medullary cancer
      of thyroid no such clear cut proof exist with papillary or follicular neoplasm of
      thyroid It's a fact that family clusters of non-medullary thyroid tumor exist, it
      requires more precise identification of genetical inheritance These clusters
      behave in a separate way and requires a more aggressive treatment for low
      recurrence rate and better prognosis.

PMID- 23120062
TI  - Parapharyngeal space lipoma.
AB  - I ipomas of the Para-pharyngeal space are rare lesions Very few cases of such
      tumors have be en reported in the literature Definitive diagnosis and decision
      regarding the surgical approach Here difficult in the pre CT scan era This was
      further compounded by the complex anatomy of the Para pharyngeal space A case of
      Para pharyngeal lipoma is being presented because of its ratity and
      characteristic radiological features After confirmation of the diagnosis the
      tumor was excised via a transcertical approach.

PMID- 23120063
TI  - Sino-nasal haemangiopericytoma.
AB  - Hemangiopericytomas are very rare soft tissue tumors of vascular origin
      featurding pericyts distributed around vascular spaces. They have unpredictable
      biological behavior and a high local recurrence rate. Silver reticulin stain is
      essential for their histologic diagnosis. Approximately one third occur in the
      head and neck. Metastases occurs in nearly one half of all cases. They are
      relatively radioresistant despite their great vascular component. Wide local
      excision of the lesion, whenever feasible and lifelong follow-up should be the
      treatment of choice.

PMID- 23120064
TI  - Haemangioma of the mandible.
AB  - Haemangioma of skeletal system are uncommon and involvement of mandible is quite
      rare A mass with occasional bleeding is the common presentation Diagnosis can be
      made by radiological finding Excision is the most effective treatment of the
      Haemangioma mandible.

PMID- 23120065
TI  - Sinonasal inverted schneiderian papilloma.
AB  - Inverted papilloma of paranasal sinuses are rare disorders of fifth & sixth
      decade of life, have been characterised by their usually benign histologic
      features, their ability to grow rapidly with bone destruction, und their tendency
      to recur if not adequately treated. We hereby report such an uncommon case of
      Schneiderian papilloma in a young patient and its management with a brief review
      of literature.

PMID- 23120066
TI  - Bilateral choanal atresia-Management with hegar's dilator.
AB  - Here we report a case of bilateral choanal atresia which is managed by transnasal
      perforation of atretic bony laminae using Hegar's uterine dilators The baby's
      airway is patent even after one yearAdvantages of using Hegar's dilator for
      correction of choanal atresia soon after birth are it is a blunt instrument, it's
      curvature fits with the curvature of the nasal cavity, dilators of increasing
      sizes are available, and as such injuries to the nasopharynx and surrounding
      areas are avoidedWe recommend this procedure as it is simple and effective in an
      emergency situation like bilateral choanal atresia Moreover this procedure is
      cheap when compared with other procedures.

PMID- 23120067
TI  - Chrome induced nasal septal perforation-An occupational hazard.
AB  - 86 patients, working in a chemical factory dealing with Chrome manufacturing job,
      were referred by Health Inspectai to F S 1 S Hospital O PD 32 patients out of
      above were found to be having Nasal septal perforation and were recommended to
      Medical Board for consideration of compensation as cases of Occupational hazard.

PMID- 23120068
TI  - Surgeons-Take care of pre and par-Surgical rituals.
AB  - Surgeons must become convinced regarding the strict adherence to a meticulous
      operating room ritual and an equally careful aseptic technique for the pre and
      post opcrative care Surgeons have lived with the risk of contracting potentially
      fatal vual diseases for the last three decades The author reviens here, the
      hazards of blood exposure and the measures that ought to be taken.

PMID- 23120069
TI  - Intranasal endoscopic DCR (END-DCR) in cases of dacryocystitis.
AB  - A prospective study on 27 cases of chronic dacryocystitis was done to see the
      outcome of management by End-DCR in Indian population and to look for advantages
      or disadvantages over Ext-DCR from available datas in literature All cases were
      diagnosed clinically by regurgitation test and lacrimal syringing In selected
      cases Jones dye test, dacryocystogram and CT scan of nose and paranasal sinuses
      (PNS) was done to confirm the site of obstruction and find out the cause Cases
      having hyperlacrumation due to other causes and epiphora due to presaccal
      stenosis were excluded Cause of NLD obstruction was atrophic rhinitis (4 cases),
      chronic sinusitis (4 cases), enlarged agger nasi cells (4 cases), faciomaxillary
      injury (1 case) and unknown in rest of cases All cases were treated by End-DCR
      under local anaesthesia Concommitent nose and PNS surgeries were done in selected
      cases where it was supposed to be the cause Average follow-up was from 3 months
      to 1 year Primary success rate was 92 6% and after revision in two cases final
      success was 96% Success rate was 100% in cases of atrophie rhinitis Major
      complication was not found in any case Our result of End-DCR was as good as Ext
      DCR Our results of End-DCR are better than those who had used lacnmal stent,
      lasers, microdebriders, dacryoendoscope and electrocautery It was finally
      concluded that end-DCR by using simple instruments is a safe and effective
      procedure.

PMID- 23120070
TI  - Oral submucous fibrosis with its possible effect on eustachian tube functions: A
      tympanometric study.
AB  - Oral submucous fibrosis (OSMF) is a chronic inflammatory condition of oral cavity
      The common sites of involvement are cheek, tongue and soft palate The
      pathological changes not only involve the mucosa and submucosa but also extend
      deeper to involve the underlying muscles Atrophic and degenerative changes in the
      tubal and paratubal muscles have already been reported and involvement of these
      muscles may lead to eustachian tube dysfunction The present study was therefore,
      planned to assess the eustachian tube functions by tympanometry in cases of OSMF
      Out of 106 ears in 53 cases, 80 ears (75 5%) showed normal type-A curve Abnormal
      tympanograms included type-B curve in 17 (16 0%) and type-C curve in 9 (8 5%)
      ears On testing the compliance of middle ear there was shift in the compliance
      peaks in 78 (73 6%) ears with +200 daPa pressure change indicating normal
      eustachian tube functions In 28 (26 4%) ears, eustachian tube functions were
      found to be affected as there was no shift in the compliance peaks Similarly on
      200 daPA pressure change in 24 (22 7%) ears there was no shift in compliance
      peaks An identical study was also carried out in 40 ears of 20 normal individuals
      The data derived were statistically much higher in the disease group Therefore,
      it was concluded that eustachian tube functions may be affected in OSMF.

PMID- 23120071
TI  - Predisposing factors and aetiology of Hoarseness of voice.
AB  - A study comprising 110 patients with hoarseness of voice was carried out between
      Jan 1998 and September 1999 to find out the predisposing factors and aetiology oj
      the condition Septic foci in nose and throat and vocal abuse were the common
      predisposing factors observed in 41 8% and 40 9% cases respectively Chronic non
      specific laryngitis was the commonest aetiology of hoarseness of voice seen in 43
      6% of cases.

PMID- 23120072
TI  - Value of ultrasonography in laryngeal and laryngopharyngeal cancers.
AB  - High-resolution sonography has improved in the past few years and has become a
      very valuable tool in the diagnosis of diseases of the head and neck.
      Ultrasonography (US) is commonly the first imaging modality after clinical
      examination. It is inexpensive, noninvasive and is easily tolerated by patients.
      It provides valuable diagnostic information with a high degree of diagnostic
      accuracy. This article provides the most up-to-date information about the
      indications, findings and limitations of high-resolution sonography in the
      evaluation of laryngeal and laryngopharyngeal cancers.

PMID- 23120073
TI  - 3-flap tympanoplasty - A simple and sure success technique.
AB  - Objective Three-flap tympanoplasty, a simple method for tympanic membrane repair,
      is recorded as an alternative method, which probably has advantages over other
      procedures and its efficacy evaluatedPatients Four hundred and fifty patients
      with subtotal or large central perforations with either an anterior bony overhang
      or vers small anterior rim of the perforation who underwent 3-flap tympanoplasty
      were included in this study Follow up period was 24 months Technique After
      removing the margin of the tympanic membrane remnant, three flaps (Superior,
      anterior and posterior) were elevated from the external auditory canal wall The
      temporalis fascia graft was then placed over the handle of malleus and all the
      three flaps were repositioned over the graftMain outcome measures The graft take
      over rate and hearing improvement postoperatively were the main outcome
      measuresResults Four hundred and twenty-five patients (94 44%) had successful
      grafts Both subjective and objective hearing improvement with a compliant
      tympanic membrane was seen in all of these patients postoperatively Mediatisation
      or lateralisation of the intact tympanic membrane did not occur Twenty-five
      patients had graft rejection, which was noted about 4 weeks after surgery and was
      due to infectionsConclusion 3-flap tympanoplasty is a simple technique with a
      very good success rate It is a useful method for busy practioners and junior
      otolaryngologists.

PMID- 23120074
TI  - Management of thyroid carcinoma-an experience in Bangladesh.
AB  - All patients (n=154) of thyroid malignancy admitted in the Otoluryngology
      Department of Bangabandhu Sheikh Mujib Medical University (former IPGMR) between
      1986 and 2000 were retrospectively analyzed to find out the extent and result of
      surgery used for thyroid carcinoma. The other objectives were to find out the
      incidence of differentiated thyroid carcinoma among the thyroid malignancy and
      also to find out the age, sex and clinical presentation of papillary and
      follicular carcinoma. Among all the thyroid malignancy (n-154), Differentiated
      Thyroid Carcinoma (DTC) was seen in 130 (84.41%) cases, where as papillary
      carcinoma occurred in 98(63.64%), and follicular carcinoma in 32(20.77%)cases. On
      the basis of risk factors, the DTC were designated as low and high risk. The year
      wise incidence of DTC revealed increasing trend from 1986 (3 cases) to 2000 (23
      cases).Among the 98 papillary thyroid carcinoma highest number of cases (35.71%)
      were seen in 31-40 year age group. The male to female ratio was 1: 1.64. In
      follicular carcinoma, highest number (35.25%) of cases were also seen in 31-40
      year age group. The male to female ratio was 1:1.66. The commonest presentation
      in papillary carcinoma was thyroid swelling (96.93%). The other presentations
      were occult thyroid (3.06%), Cervical lymph node metastasis (38.77%) and distant
      metastasis (2.04%). In Follicular carcinoma, the presentations were thyroid
      swelling (100%), Cervical lymph node metastasis (6.25%) and Distant metastasis
      (21.87%).In this series, low risk DTC were treated by Lobectomy & Isthmusectomy
      plus Thyroxin. In low risk group the rate of recurrence was 6.89% and the
      mortality was nil in five years follow-up. Except two inoperable cases, all high
      risk patients were managed by Total thyroidectomy (with or without neck
      dissection, plus removal of metastatic lesion when required) with Radioiodine
      ablation plus Thyroxin. . The rate of recurrence was 7.81% and mortality was
      1.56% in high risk group in similar period of time.Vocal cord palsy were noted in
      5 (3.84%) unilateral, and inane (0.76%) bilateral cases. Hypoparathyroidism was
      found in 4.61%.

PMID- 23120075
TI  - Ear, nose and throat manifestations in pediatric chronic renal failure patients
      undergoing peritoneal dialysis.
AB  - Ear, Nose and Throat manifestations have been frequently observed in patients
      with chronic renal failure. Many factors viz. ototoxic drugs, associated
      conditions of renal failure such as electrolyte imbalance, alteration in blood
      urea etc. have been implicated for these manifestations. The present study has
      been conducted to evaluate ear, nose and throat manifestations in thirty
      pediatric patients (age group 4-16 year) of chronic renal failure undergoing
      peritoneal dialysis. Probable patho-physiology and treatment of ENT
      manifestations has been discussed. The remarkable findings in all these cases
      were the high blood urea level. Most of these manifestations were markedly
      improved by correction of the renal functions and ideal therapeutic measures.

PMID- 23120076
TI  - An epidemiological study on children with syndromic hearing loss.
AB  - OBJECTIVES: To study the epidemiological factors in children with syndromic
      hearing loss. STUDY DESIGN: Interview based prospective study. SETTINGS: Govt.
      ENT Hospital, AYJNIHH, NIMH-SEC, and Schools for the Deaf-in Hyderabad and
      SecunderabadPatients: Children aged below 14 years, with hearing loss, their
      parents/guardians. INTERVENTION(S): The study revealed type and degree of hearing
      impairment. In high risk groups genetic counseling was offered. RESULTS:
      Epidemiological studies were carried out in 743 children below 14 years with
      hearing impairment and 138 (18.57%) were found to have syndromic deafness.
      Majority of the children with hearing loss have an association of ocular
      abnormality (22.46%, n=31) followed by skeletal anomalies 14.49% (n=20) and
      dental anomalies (10.86%). We observed 24 cases (3.21%) with genetically well
      recognized syndromes. CONCLUSION: Data is generated on epidemiological and
      etiology of Hearing Impairment. Hearing Impairment is due to both environmental
      and genetic causes. Environmental factors in 17 (13.77%), genetically inherited
      21 cases (15.22%) and the cause is not known in the remaining cases. Such a data
      is required in order to offer genetic counseling to reduce the genetic burden.

PMID- 23120077
TI  - Maxillary swelling - A rare presentation of solitary plasmacytoma.
AB  - Plasmacytoma is not a rare entity; it usually presents as bone pain (70%) or
      susceptibility to infection e. g. . pneumonia or pyelonephritis, but its
      presentation as isolated maxillary swelling is a rare entity.Here, a 25 years
      young male presented with right maxillary swelling. After radiological,
      histopathological and biochemical investigation, it was diagnosed as
      plasmacytoma. The modalities of treatment with review of literture is discussed
      in this report.

PMID- 23120078
TI  - Pleomorphic adenoma of submandibular gland.

PMID- 23120079
TI  - Sub-lingual dermoid cyst.
AB  - Dermoid cysts are commonly found through out the body . In the oral cavity,
      though rare, dermoids commonly present sublingually. Typically, they present as
      slow growing masses, causing elevation of the tongue, interference with speech
      and swallowing. We report a case of sublingual dermoid cyst in a two years old
      female child.

PMID- 23120080
TI  - Metastatic choniocarcinoma of the nasal cavity-presenting as intractable
      expistaxis.
AB  - There are numerous known causes of epistaxis Neoplasms of the nose and paranasal
      Sinuses as causes of epistaxis are rare Choriocarcinoma is a highly malignant
      germ cell tumor occurring in the reproductive and midline regions of the body
      Metastasis may be principally by the lymphatic route as in other germ cell tumors
      but chonocarcinoma is known for Us propensity to spread haematogenously We report
      a rare case of metastatic chonocarcinoma of the nasal cavity presenting with
      intractable epistaxis in a 32 year old African gentleman which rapidly proved
      fatal The literature is briefly reviewed.

PMID- 23120081
TI  - Malignant melanoma of the nasal cavity.
AB  - Malignant melanomas of the sinonasal mucosa are very uncommon, presenting
      frequently in advanced stages with usually a fatal course. Diagnosis becomes more
      difficult if it is amelanotic variety. Radical surgery is constrained because of
      increased morbidity & cosmesis, moreover radiotherapy and chemotherapy have
      little role if any to play. A case of 60 years old male who presented with nasal
      mass and epistaxis finally diagnosed as melanoma on histolopathology. Some other
      important aspects of this rare tumor are discussed here.

PMID- 23120082
TI  - Rhinofacial zygomycosis caused by conidiobolus coronatus.
AB  - Fungal infections are common in a tropical country like India. Among the
      Zygomycosis infections, those caused by Mucorales are more prevalent. However,
      there exists another order of zygomycetes, the Entomophthorales, which rarely
      cause clinical disease. We report a rare cause of fungal infection of the maxillo
      facial region and the oropharynx in a previously healthly male adult caused by
      Conidiobolus coronata of the order Entomophthorales to highlight the clinical
      presentation and treatment of this rare, chronic, indolent form of fungal
      infection.

PMID- 23120083
TI  - Schwannoma of the brachial plexus presenting as a cystic swelling.
AB  - Schwannomas are benign nerve sheath tumours. A small percentage of these tumours
      arise from the brachial plexus. Cystic degeneration and hemorrhagic necrosis can
      occur in these tumours in up to 40% of the cases. Detailed preoperative
      evaluation and careful dissection during surgery will avoid post operative
      neurological complications. We report a case of schwannoma of the brachial plexus
      presenting as a cystic neck swelling which was successfully managed by us.

PMID- 23120084
TI  - Oropharyngeal leiomyosarcoma.
AB  - A unique case of Oropharyngeal leiomyosarcoma in a 32 years old male is presented
      with the review of literature The details of clinical, radiological,
      histopathological and operative findings are discussed The treatment of choice is
      complete tumor removal The patient was symptom free with no evidence of loco
      regional or distant metastasis at one-year follow up.

PMID- 23120085
TI  - Spontaneous expulsion of an interesting long standing metallic foreign body (iron
      nail) from left main bronchus.
AB  - Worldwide experiences of spontaneous expulsion of foreign body bronchus ranges
      between 2-4%. We are reporting here an unusual and interesting case of a long
      standing irregular metallic large foreign body in left main bronchus, which was
      lying there for more than one month duration and suddenly while preparing the
      patient for endoscopic removal, it was expelled out spontaneously. These types of
      incidences make us wiser to keep the rare and remote possibility in mind,
      especially when there is a remote but dangerous possibility of subglottic
      lodgement of foreign body with spontaneous expulsion.

PMID- 23120086
TI  - Fungal infections and cavernous sinus thrombosis.
AB  - Rhino - Cerebral Mucormycosis, in uncontrolled diabetics, is a common entity
      Cavernous Sinus Thrombosis, secondary to fungal involvement is rarely encountered
      Two cases with fulminant spread are reported highlighting the symptoms, signs,
      and therapeutic modality.

PMID- 23120087
TI  - Penetrating injury neck - An unusual presentation.
AB  - In a patient presenting with a penetrating injury of the neck, the problems
      contemplated can be very many and life threatening as well. This case
      demonstrates an unusual presentation of only a simple rupture of the
      Sternocleidomastoid muscle sparing all the vital structures beneath it following
      the penetration of a metallic rod of approx. 1.5 cm diameter in the neck.

PMID- 23120088
TI  - Post operative sensorineural hearing loss after middle ear surgery.
AB  - Mild Sensorineural hearing loss subsequent to middle ear surgery has till today
      been an important complication to middle ear surgery inspite of advances in
      surgical techniques, operative instruments, monitoring devices and better
      treatment options. Lack of proper knowledge about this problem is because of
      under reporting of exact magnitude of hearing loss on account of difficulty in
      measuring hearing threshold of patients in immediate postoperative period as it
      may lead to post operative infection and discomfort to the patient.In our study
      of 80 cases carried out at ENT department, Baroda Medical College and S.S.G
      Hospital, Baroda, we have utilized weber's lateralisation principle and measured
      bone conduction thresholds of patients undergoing middle ear surgery for
      evaluation of postoperative Sensorineural loss as a result of middle ear surgery.
      Probable causes of post operative hearing loss in a patient undergoing middle ear
      surgery are, noise due to drills, continuous suction irrigation, vibrations,
      inner ear injury, manipulation of ossicles and a few unknown reasons.

PMID- 23120089
TI  - Role of endoscope and microdebrider in the excision of skull base schwannoma
      Arising from the sphenoid sinus.
AB  - A 54 year old lady presented with complaint of right sided nasal obstruction for
      the past 4 years which was persistent and total. Examination revealed a pale mass
      in the posterior half of the nasal cavity obscuring the choana. It was firm in
      consistency, pale with a smooth surface. The Cranial nerves were normal.
      Clinically there was no evidence of spread into the maxillary sinus or orbit or
      regional lymphadenopathy. Ophthalmologist's opinion was sought.

PMID- 23120090
TI  - Overview of fungal rhinosinusitis.
AB  - The incidence of fungal rhinosinusitis has increased to such extent in recent
      years that fungal infection should be considered in all patients with chronic
      rhino sinusitis. In India though the disease was reported earlier only from
      northern regions of this country, nowadays the disease is increasingly diagnosed
      from other parts as well. The disease has been categorized with possible five
      types: acute necrothing (fulminant), chronic invasive, chronic granulomatous
      invasive, fungal hall (sinus mycetoma), allergic. The first three types are
      tissue-invasive and the last two are non-invasive fungal rhinosinusitis. However,
      the categorization is still controversial and open to discussion. Chronic fungal
      rhinosinusitis can occur in otherwise healthy host and Aspergillus flavus is the
      common etiological agent in Indian scenario. The pathophys iologic mechanism of
      the disease remains unclear. It may represent an allergic IgE response, a cell
      mediated reaction, or a combination of two. Early diagnosis may prevent multiple
      surgical procedures and lead to effective treatment. Histopathology and radio
      imaging techniques help to distinguish different types and delineate extension of
      disease process. Culture helps to identify the responsible etiological agent. The
      presence or absence oj precipitating antibody correlates well with disease
      progression or recovery. The most immediate need regarding management is to
      establish the respective roles of surgery and antifungal therapy. Non-invasive
      disease requires surgical debridement and sinus ventilation only, though,
      additional oral or local corticosterold therapy may be beneficial in allergie
      type. For invasive disease, the adjuvant medical therapy is recommended to
      prevent recurrence and further extension. Itraconazole has been found as an
      effective drug in such situation. Patients with acute neerotizing type require
      radical surgery and amphotericin B therapy.

PMID- 23120091
TI  - A study of 272 cases of endoscopic dacryocystorhinostomy.
AB  - 272 Patients with obstruction in nasolacrimal duct were treated by endoscopic
      nacryocystorhinostomy (DCR). The results were compared with that of external DCR
      and Endoscopic DCR without stent. In our study Endoscopic DCR with stening had
      better results. Endoscopic DCR with stenting has several advantages over the more
      conventional external approach and Endoscopic DCR without stenting. Results at 4
      years of follow up have been good that is 98.6% patients were relieved of
      symptoms completely.

PMID- 23120092
TI  - Community oriented research program for prevention of deafness with special
      stress on children - A preliminary report.
AB  - A study of community- oriented multilaleral study was carried out in rural
      community of eastern Nepal where in total of 2564 patients were screened out and
      it revealed that multi nutritional deficiency comprised of 20% along with
      unsatisfactory or incomplete immunization was recorded in 45%. Children up-to 14
      years of age (1223) were considered for this study. 5-14 years of age were the
      must vulnerable for ear diseases (50.16%). 61% children were living in over
      crowded dwellings. The hearing analysis established that the number of conductive
      deafness were prevalent in 62.46% in comparison to sensory-neural hearing loss
      2.40% and mixed hearing loss (0.18%). Due to better ear care, Otorrhoea was under
      control in 67% cases and so was the conductive deafness improved.

PMID- 23120093
TI  - A clinical study of benign tumours of nose and paranasal sinuses.
AB  - In this prospective study, comprising of 30 cases, various benign tumours, both
      common and rare are compiled. The cases were selected in the OPD of Kempegowda
      institute of medical sciences, one of the tertiary referral centres in Bangalore.
      The sample consists of patients in the age group 9 months to 60 years. The study
      also compares sex differences,symptomatology and the relative incidence of
      various rumours. The commonest site was nasal cavity, followed by paranasal
      sinuses and external nose. They occur commonly in second and third decades with
      predominance in males. Epithelial tumours were less common when compared to non
      epithelial tumours. All masses should be subjected to histopathological
      examination for proper management All cases should be followed up for as long as
      two years for better assessment treatment and response.

PMID- 23120094
TI  - Determinants of sensorineural hearing loss in chronic middle-ear disease.
AB  - A statistical study was carried out on SNHL in CSOM. The study group consisted of
      1,828 patients suffering from CSOM who underwent surgery at our centre from 1982
      to 2001, out of these 510 cases with unilateral CSOM were selected for this study
      by a strict selection criteria so as to eliminate covariables such as exposure to
      acoustic trauma, head injury, previous ear surgery and hereditary causes. The
      healthy ear served as control. We determined the average SNHL in relation to the
      age of onset, duration of disease, examining it in relation to other eventual
      aural complications such as cholesteatoma, ossicular chain erosion und
      otorrhea.On the basis of data obtained we observed consistent co-relation between
      severity of SNHL and duration of the disease, presence of cholesteatoma,
      ossicular erosion, attic and subtotal perforations. These findings suggest that
      more severe middle ear disease may result in SNHL and thus early intervention in
      cases of chronic suppurative Otitis media is desired.

PMID- 23120095
TI  - Antrochoanal polyp - Validating its origin and management by endonasal endoscopic
      sinus surgery (eess).
AB  - AIM AND OBJECTIVES: 20 fresh cases of Antrochoanal Polyps were subjected to EESS
      for studying the site of origin and to validate its efficacy. STUDY DESIGN: This
      was a prospective study in which the cases were subjected to surgery and were
      followed; up for evaluation of results. METHODS: The surgery performed was an
      endoscopic endonasal sinus surgery preceded and followed by transcanne sinuscopy.
      Results/Findigs: The age at the time of presentation ranged from 7-35 years. Male
      to female ratio was 1:1:5. Occurrence Antrochoanal Polyp was 1.5 times more
      common on the left side. The mean duration of symptoms was 3 years. The main
      presenting symptom was unilateral nasal obstruction in 100% of cases. Allergic
      symtomps.were noticed in 10%. Vasmotor symptom were present in 15% of the
      patients. Antroscopy revealed the antral part.to be cytic in 100% of the cases.
      The site of origin of the polyp could be ascertained in only 12 out of 20 cases;
      in 7 of them it acrose from the infrolateral wall of maxillary sinus, in 2 from
      the infromedial wall und in 2 it appeared to arise from the supromedial wall
      while in 1 from margin of the ostium. Post-surgery intra-natral remnants were
      found in 3 out of 20 cases i.e. in 15% of them. In two cases it was removed
      through maxillary ostia but in one case removed through transcanine route.
      CONCLUSIONS: Endoscopic Sinus Surgery is the best modality of treating
      Antrochoanal Polyps. We report a success rate of 95% in our series.

PMID- 23120096
TI  - Laser perception by patient in ent practice.
AB  - Laser will shape the medical science in the 21st century. So we have planed a
      study in Down Town Hospital of Guwahati about laser perception of the patient
      attending EST department of this hospital. This type of survey is very important
      for the doctors because patient'perception is very important in all the branches
      of medicine specially when we use new surgical tools. this also gives feed back
      to the surgical tools manufacturers on which directions their work should
      progress.

PMID- 23120097
TI  - Medialization laryngoplasty-A study of 15 cases.
AB  - Type I thyroplasty has become a primary surgical choise for voice restoration in
      patients with glottal incompetence due to vocal cord palsy. In this study 15 such
      cases of different etiologies were taken up for medializatioin laryngoplasty and
      their preoperative und post operative. voice assessment were done. We found that
      there was significant improvement in loudness: hoarseness and breathiness.
      Postoperative maximum phonation time also increased to normal limits. There were
      no major complications of the surgery.

PMID- 23120098
TI  - Malignant fibrohistocytoma of the larynx.

PMID- 23120099
TI  - Kimura's disease: Rare cause of head & neck swelling.
AB  - Kimura 's disease presents as subcutaneous painless swelling in head and neck
      region often mimicking inflammatory or neoplaitic disease. This case report draws
      attention of otolaryngologist-head & neck surgeons to recognise this rare
      clinical entity.

PMID- 23120100
TI  - Fibromyxoma maxilla.

PMID- 23120101
TI  - Esthesioneuroblastoma as a collision tumor.
AB  - Esthesioneuroblastoma is an uncommon malignant neoplasm of nose and paranasal
      sinuses. Esthesioneuroblaslvma presenting as a collision tumour is very rare. The
      case of such a rare presentation is being reported here in a patient with
      previous history of squamous cell carcinoma uvula, post irridiatted; who now
      developed a bleeding nasal mass which proved to be a collision timour c ontaining
      both squamous cell carcinoma and Esthesioneuroblastoma on biopsy.

PMID- 23120102
TI  - Rhinolith: An unusual presentation.
AB  - A case of rhinolith in a 60 years old male prsenting with palatal performation
      is, presented alongwith a brief discussion on the pathogenesis and treatment.

PMID- 23120103
TI  - Extranodal non-Hodgkins lymphoma of larynx.
AB  - Non-Hodgkins lymphoma is found in the older age group with extranoda involvement
      more commonly seen than in Hodgkins lymphomna. It isusually of B-cell type which
      has a better prognosis than T-cell type, Extranodal Non-Hodkin's lymphomas of
      larynx are rare. they can present as isolated lesions in larynx or associated
      with multiple involvement. They are usually found in the supraglottic region of
      the larynx. We present a case of 70-year-old female with extranodal Hodgkins
      lymphoma of epiglottis with metastasis in the liver.

PMID- 23120104
TI  - Waardenburg syndrome.
AB  - We report a case of Waardenburg syndrome in a female child aged 2yrs. Petrus
      Johannes Waardenburg(1) , a Dutch Ophthalmologist in 1951 described individuals
      with retinal pigmentary differences who had varying degrees of hearing loss and
      dystopia canthorum (i.e., latral displacement of inner canthi of eyes). The
      disease runs in families with a dominant inheritance pattern with varying degree
      of clinical presentation. Patient usually present with heterochromic iris,
      pigmentary abnormalities of skin and hearing loss.Here we report a patient having
      severe bilateral hearing loss with pigmentary disturbances.

PMID- 23120105
TI  - Anterior septal chondroma.
AB  - The cartilaginous tumours of the nasal septum are very rare and almost always
      arise from the posterior part. Considering the extremely rare occurrence of
      chondroma arising from anterior part of septum we report such a case. The tumour
      was well defined, homogenous in appearance and was widely excised through lateral
      rhinotomy approach. The least accepted traumatic etiology seems to be most
      appropriate for the oncogenesis in this case. We advocate a thorough
      histopathological examination of the tumour in to-to in order to appreciate early
      sarcomatous changes. This report also reviews the relevant literature.

PMID- 23120106
TI  - Actinomycosis of the parotid gland.
AB  - - Actinomycosis is a slowly progressive infection caused by anaerobic bacteria
      with relatively decreasing incidence now-a-days. The Parotid gland is a quite
      rere site to be involved in cervico-facial actinomycosis as compared to the other
      sites in the face & neck region. We report a successfully managed case of
      Actinomycosis involving the parotid gland.

PMID- 23120107
TI  - An unusual foreign body (Big Metallic Nut) in the nasopharynx of an infant.
AB  - Foreign body in the nasopharynx is an extremely rare conidition; however a big
      metallic nut in the masopharynx of an infant of eight- months has not been
      previously reported in literature. We report an unusual case where an eight-month
      old child introduced a big metallic nut through the mouth and was lodged in the
      nasopharynx, with a brief review of literature regarding the diagnosis and
      management of such case.

PMID- 23120108
TI  - Cutaneous T cell lymphoma with multiple oral lesions.
AB  - Cutaneous T cell lymphoma is a type of non Hodgkins lymphoma occurring rarely
      (two-three percentage of NHL) and that with an ENT manifestation is much more
      rare. We present here a case of cutaneous T cell lymphoma presenting with
      multiple skin lesions and oral and oropharyngeal ulcerations.

PMID- 23120109
TI  - Chondrosarcoma of the nasal septum.
AB  - Chondrosarcoma of the head and neck region are relatively uncommon, arising
      rarely in the naval septum. The reported cases of nasal septal chondrosarcomas
      are extensive lesions with involvement of paranasal sinuses, orbit or skull base
      at the lime of diagnosis. Those limited to the nasal cavity is extremely rare and
      to date there has been one case report in English language literature. We present
      a case of chondrosarcoma of the nasal septum with involvement of the nasal cavity
      alone and no evidence of bony erosion. Initial multiple biopsies showed mature
      chondromatous areas with no atypia. The patient had wide excision of the tumour.
      The final biopsy of the excised specimen revealed foci of well-differentiated
      chondrosarcoma. Wide surgical excision with adequate margins should be considered
      as the treatment of choice in lesion of nasal septum even if initial biopsies are
      negative for malignancy. Hence this case report.

PMID- 23120110
TI  - Allergic fungal sinusitis- A clinico-pathological study.
AB  - The co-existence of fungal elements in allergic nasal Polyposis, has given rise
      to a distinct clinical entity known as 'Allergic fungal sinusitis ' (AF'S). Many
      a time, these fungal elements may not be diagnosed pre-operatively by routine
      diagnostic nasal endoscopy or CT scan of paranasal sinuses, due to the florid
      presentation of nasal polyps, which usually obscure the underlying fungal
      pathology. The diagnosis is often made intra-operatively. The post-operative
      confirmation of AFS is by histopathology, fungal smear, fungal culture, allergic
      murin study and fungal specific IgE titres. We report a series often such cases
      done in our institution, which highlight that AFS should be considered as a
      differential diagnosis in Sinonasal Polyposis cases, for their effective
      management.

PMID- 23120111
TI  - Arterio venous malformation of the nose and forehead.
AB  - Congenital arterio-venous malformations of the head and neck are uncommon lesions
      encountered in clinical practice. They can have a range of clinical effects from
      mild disfigurement to cardiac failure. Treatment of these lesions poses a
      challenge to the surgeon due to their extreme vascularity and high incidence of
      recurrence. Highly selective arterial embolization and surgical resection offer
      the best chance for cure. The ease presented is that of a congenital a v
      malformation of the face, which was treated successfully by surgical excision.

PMID- 23120112
TI  - Giant frontoethmoid osteoma nasoendoscopic resection using intranasal drill.
AB  - Ostenmas of the paranasal sinuses are common. Most arc however asymptomatic and a
      chance radiographic finding. In this article we present a less invasive yet safe
      and effective approach to treatment. The 45 degrees  nasoettdoscopic approach
      using an intranasal drill provides a good operative field and is safe and
      effective technique ,with the potential to become the treatment of choice in
      selected cases.

PMID- 23120113
TI  - Anterior skull base: High risk areas in endoscopic sinus surgery in chronic
      rhinosinusitis: A computed tomographic analysis.
AB  - Computed Tomography (CT) scan of nose and paranasal sinuses play a key role in
      preoperative evaluation of patients undergoing endoscopic sinus surgeries (ESS)
      for chronic rhinosinusitis. The asymmetry of ethmoid fovea olfactory fossa,
      anatomical variations of lateral lamella and course of anterior ethmoid artery
      are critical in ESS as it may predispose to dangerous consequences like
      hemorrhage. CSF leak and intracranial complications. A prospective study was done
      on 75 patients of clinically and diagnostically proven chronic rhinosimusits. The
      coronal CT scan was evaluated with special attention to anatomical variations of
      anterior skull base including ethmoid fovea, olfactory fossa, lateral lamella and
      course of anterior ethmoid artery. The endoscopic surgeon's awareness of these
      variations and its role in preventing complications are highlighted.

PMID- 23120114
TI  - Tragal perichondrium and cartilage in reconstructive tympanoplasty.
AB  - The objective of study was to assess the efficacy of tragal perichondrium and
      cartilage, the functional capacity in restoring hearing acuity, it's mechanical
      survival, it's extrusion rate and it's functional integrity in tympanomastoid
      reconstruction. The study was conducted at K.E.M. Hospital, ENT department during
      1980 to 2000. The study presents six hundred ear operations of varied middle ear
      pathology using tragal cartilage and perichondrium as a choice graft. The
      technical advantages of tragal perichondrium graft in myringoplasty,
      ossiculoplasty, osseusplasty, and mastoid cavity obliteration are discussed. We
      have recorded our observations and results and concluded that tragal
      perichondrium and cartilage is an ideal graft material for reconstructive
      tympanoplasty.

PMID- 23120115
TI  - Diagnostic significance of nasal eosinophilia in allergic rhinitis.
AB  - BACKGROUND: Nasal eosinophilia is one of the potential tests for substantiating
      the diagnosis of allergic rhinitis. OBJECTIVE: The aim was to establish the
      validity of nasal eosinophilia in allergic rhinitis, to study it's various
      clinical correlates and interpret it in context of skin sensitivity pattern.
      STUDY DESIGN: Prospective cased study. SETTING: Hospital based. PATIENTS: The
      patients were selected on the basis of history and clinical examination and were
      from the Himalayan region. INTERVENTION: Diagnostic. METHODS: The patients and
      the equal number of controls, were subjected to nasal smear for eosinophilia and
      intra-dermal skin tests to various allergeus. RESULTS: Overall, eighty percent of
      nasal smears were positive in various degrees among the cases. Around eighty
      eight percent of cases showed both smear and skin test positivity, thereby
      signifying a high degree of harmony among them and further validating and
      confirming the diagnosis of allergic rhinitis. CONCLUSION: Nasal eosinophilia was
      found to be a useful diagnostic test in allergic rhinitis, with a moderately high
      sensitivity and a high specificity.

PMID- 23120116
TI  - Facial translocation approach to infratemporal fossa and cranial base in
      extensive angiofibroma: A review of 7 cases.
AB  - Angiofibroma extending to infratemporal fossa, orbit and middle cranial fossa is
      a difficult problem for a surgeon to tackle. Traditional extracranial excision
      with radiotherapy for the intracranial extension was practiced for a long time
      with variable results. Different approaches to remove such a tumour are described
      but most of them are not free from resultant morbidity in the form of facial
      asymmetry and incomplete tumour removal. Facial translocation approach
      facilitates complete tumour removal without cutting through the tumour thereby
      reducing per-operative blood loss. It also avoids facial asymmetry as the
      zygomatico-orbito-maxillary bony complex is replaced after the tumour removal. We
      present a review of seven cases with the results. The surgical steps, advantages,
      disadvantages and the complications are discussed.

PMID- 23120117
TI  - Intratympanic dexamethasone application in Meniere's disease-Is it superior to
      conventional therapy?
AB  - OBJECTIVE: To compare the efficacy of conventional medical treatment versus
      transtympanic dexamethasone application into middle ear as treatment modality in
      Meniere's disease. STUDY DESIGN: Prospective randomized study. SETTING: Tertiary
      referral centre. METHOD: Forty patients of Meniere's disease were treated, 20 by
      conventional method and 20 by transtympanic dexamethasone applications.
      INTERVENTION: Theraputic. RESULTS: Vertigo control of 85% achieved in study group
      when compared to 80% in control group, 15% of patients had hearing improvement in
      study group while 10% had hearing improvement in control group. Aural fullness
      and tinnitus control were identical in both groups. CONCLUSIONS: Both modalities
      of therapy were found to have almost equal efficacy, with Intra tympanic steroid
      (ITS) therapy having an edge over conventional therapy in cases with severe
      attacks and shorter duration of symptoms.

PMID- 23120118
TI  - Clinical study of maxillofacial trauma in Kashmir.
AB  - The present study of 206 cases admitted with maxillofacial trauma reveals that
      road traffic accidents account for 67 cases (32.52%) followed by missile injury
      55 cases (26.70%) fall 39 cases (18.93%) bear slap 21 cases (10.19%) assault 14
      cases (6.80%) and others 10 cases (4.86%) The cases of maxillofacial trauma were
      also analysed according to age and sex distribution and type of injury.It was
      found that road traffic accidents was the commonest cause of injury in males
      (34.21%) and in females the commonest cause of injury was fall (35.18%). Maximum
      number of cases 72 (34.95%) were found in the age group of 21-30 years and the
      mixed type of injury was common (60.68%) and mostly involving the middle third of
      face. Difficulty in chewing was the commonest presentation in road traffic
      accident.

PMID- 23120119
TI  - Pre-cancerous changes in the nasal mucosa of atrophic rhinitis: A preliminary
      report.
AB  - Metaplasia is a known predisposing factor to malignancy. As squamous metaplasia
      is a regular feature of atrophic rhinitis, its relationship with cancer is
      examined in this cross-sectional study. Random punch biopsies of nasal mucosa
      obtained from 14 patients (6 male and 8 female) suffering from primary atrophic
      rhinins were studied. Squamous metaplasia was noted in 64%. Epithelial dysplasia
      and in-situ malignant transformation were noted in one patient each. This
      preliminary report suggests that the association of atrophic rhimitis and pre
      cancerous lesions appear to be more than coincidental and it deserves further
      studies.

PMID- 23120120
TI  - CT-Cephalometry-A study in Indian population.
AB  - Determination of obstructive site in obstructive sleep apnoea (OSA) is of
      paramount importance is planning the management. Cephalometric evaluation of
      lateral X-rays when combined with clinical assessment and fibreoptic examination
      of the airway helps in locating the site of obstruction. The usual technique of
      cephalometry has been modified so as to give a better delineation of the soft
      tissues. Holding a 2mm card board in the mouth and using barium paste helped in
      more accurate calculations. Using our technique, various parameters have been
      quantified and a number of controls were studied and normal range derived.
      Further improvement in cephalometry has been done by using C.T. cephlometry
      topogram technique. A topogram is a scan done on a running table top cranio
      caudally. Using the topogram technique 38 OSA patients were evaluated for all the
      parameters. The technique, its advantages over traditional cephalometry and the
      values obtained in the study are discussed in this paper.

PMID- 23120121
TI  - Benign lesions of larynx-A clinical study.
AB  - OBJECTIVE: A climical study was undertaken to analyze the age, sex distribution
      and symptomatology, sites of involvement and the prognosis of the common types of
      benign lesions of larynx. STUDY DESIGN: A five year retrospective study from 1997
      to 2002. SETTING: KMC Hospital Attavar -A tertiary referral hospital. PATIENTS: A
      total of 42 patients with benign laryngeal lesions were included based on
      symptomatology such as hoarseness of voice, foreign body sensation, throat pain,
      neck mass and cough and with positive clinical findings on indirect laryngoscopy
      and neck examination. The patients ranged from 7-80 years. All non-operative
      cases and malignant cases were excluded. Diagnostic hematological and
      radiological investigations and therapeutic microlyryngoscopic procedures were
      employed. RESULTS: A male preponderance with M:F ratio of 3?1 was observed.
      Majority of the patients were in the 30-40 age group. Vocal polyps were the
      commonest type of lesion. In our study, hoarseness of voice, cough, foreign body
      sensation and throat pain proved to be the commonest symptoms. CONCLUSIONS: Micro
      laryngeal surgery and voice rest offer a cost effective, useful and safe method
      for management of benign laryngeal lesions.

PMID- 23120122
TI  - Eustachian tube function after transmyringeal ventilation.
AB  - This study anus at determining the effect of transmyringeal ventilation on
      Eustachian tube functions. Seventy ears clinically diagnosed as having otitis
      media with effusion or grade I and II retraction of pars-tensa of tympanic
      membrane were treated with antiallergics, decongestants, mucolytics, and
      antibiotics as required for maximum upto three months. In forty-five ears that
      showed neither symptomatic nor audiometric improvement, transmyringeal
      ventilation was restored by myringotomy and ventilation tube insertion. There
      after, Eustachian tube functions were assessed by using pressure equilibration
      test. The post-operative audiograms showed mean hearing gain of 16. 6 dB (S D+/
      7.9) in majority (96%) of the ears. At first week 93% ears could not either
      totally or partially equilibrate positive or negative pressure. The percentage in
      the poor function group remained 91% even at the end of 6 months showing no
      significant effect of ventilation tube insertion on active ET functions.

PMID- 23120123
TI  - Fat plug myringoplasty.
AB  - Fat plug myringoplasty is a technique described to repair small dry central
      tympanic membrane perforations. It is a simple office procedure with minimal
      morbidity to the patient. The present study is a prospective review of 18
      patients who underwent 20 fat plug myringoplasty procedures over three and a half
      year penod. The success rate of 90% closure of tympanic membrane was achieved at
      an average of six months follow up. The patient selection criteria have to be
      adhered strictly to gain good outcome. The study concludes that fat plug
      myringoplasty is a simple, quick and minimally invasive procedure which can be
      done as OPD procedure resulting in a safe and dry ear.

PMID- 23120124
TI  - X-Rays in the evaluation of adenoid hypertrophy: It's role in the endoscopic era.
AB  - OBJECTIVES: To evaluate the reliability of X-rays in the diagnosis of adenoid
      hypertrophy and to validate this with flexible nasopharyngoscopy which is the
      existing gold standard. METHOD: Lateral radiograph of the neck and a flexible
      nasopharyngeal endoscopy was done to evaluate adenoid enlargement in children
      aged 3-12 years who were included in a S week randomized double-blind placebo
      controlled study for the effect of beclomethasone in adenoid hypertrophy. These
      were graded independently by both the co-investigor and investigator X-ray and
      nasal endoscopy for reevaluation of adenoid size was done at the completion of
      the study. Variables of both the procedures were scored at the beginning and end
      of the study. The agreement between the two groups was assessed using weighted
      kappa statistic. RESULTS: There were 26 patients in the study, 17 of them had
      complete correlation between the X-ray and endoscopy findings. The agreement
      between these findings was statistically significant (p<01) with the weighted
      kappa 0.51. CONCLUSION: This study shows that lateral X-rays of the neck, besides
      being a noninvasive procedure, still remains a very reliable and valid diagnostic
      test in the evaluation of hypertrophied adenoids.

PMID- 23120125
TI  - Acoustic analysis of subjects with vocal cord paralysis.
AB  - Theoretically, there should be a close relationship between the vibratory pattern
      and acoustic output. The study aims at differentiating unilateral vocal cord
      paralysis (VCP) from normal subjects and also between right VCP and left VCP
      based on the acoustic analysis of the subjects voice. The study also aims at
      comprehensively investigating the phonatory disturbance resulting from VCP on the
      Indian population.Results indicate that statistically significant differences
      were found among the following acoustic parameters: fluctuation per sec, in
      fimdamental frequency (fo), fluctuation per sec, in amplitude, extent of
      fluctuation in fo, extent of fluctuation in amplitude, jitter ratio, jitter
      factor, shimmer. Psigma and maximum phonation duration in differentiating
      unilateral VCP from normal subjects. Also the acoustic parameters: fluctuation
      per sec, info, extent of fluctuation in fo and Psigma could statistically
      differentiate between right VCP and left VCP. It can be concluded that the above
      parameters can be successfully used for diagnosing VCP and also the type of VCP.
      This is of particular significance in difficult to visualize patients and to
      monitor the therapeutic outcomes of vocal rehabilitation, following unilateral
      vocal cord paralysis. These results need to be further clinically validated by
      using a larger number of subjects.

PMID- 23120126
TI  - Non-inherited manifestation of bilateral branchial fistulae, bilateral pre
      auricular sinuses and bilateral hearing loss: A variant of branchio-oto-renal
      syndrome.
AB  - A rare manifestation of branchio-oto-renal like syndrome as an isolated finding
      with normal chromosomal analysis in a 6 year old child with bilateral branchial
      simises, bilateral pre-auricular simuses, bilateral auricular malformation, and
      bilateral hearing loss is presented here.

PMID- 23120127
TI  - Encephalocoele as a complication of intranasal surgery.
AB  - Intranasal encephalocoele can be congenital or acquired as a consequence of
      injury to the floor of anterior cranial fossa disrupting dura resulting in
      herniation of brain tissue in the nasal cavity. Authors came across a case of
      encephalocoele as a complication of intranasal polypectoury. We are reporting
      this case due to its rareness.

PMID- 23120128
TI  - Diagnostic dilemma in bilateral multiple cervical lymphadenopathy.
AB  - Patient presenting with cervical lymph node enlargement is common in
      Otorhinolaryngology out-patient department of different hospitals of India. In
      many cases it becomes difficult to know the cause of lymphadenopathy without
      doing a battery of investigations. Often on fine needle aspiration cytology,
      lymph node in the neck is found to be metastatic, but site of prinary tumour
      becomes difficult to find out. Here a case in presented with multiple bilateral
      cervical lymphadenopathy with a diagnostic dilemma where the diagnosis changed
      repetitively from one doctor to another and from one laboratory to another.

PMID- 23120129
TI  - Auditory brainstem implantation: The first Indian experience.
AB  - Multichannel auditory brainstem implants (ABI) are currently indicated for
      patients with neurofibromatosis type II (NF2) involving both vestibulocochlear
      nerves. The ABI helps bypass the damaged cochlear nerves and restores a level of
      auditory sensation via the electrical stimulation of the cochlear nucleus. The
      implant is usually placed in the lateral recess of the fourth ventricle at the
      time of tumor resection to stimulate the cochlear nucleus. We report a case of
      ABI done on a 15-year-old girl with bilateral vestibular schwannomas.

PMID- 23120130
TI  - KTP/532 laser excision of trichoepithelioma of the ear.
AB  - A rare case of trichoepithelioma of the external ear is presented Conventional
      excision with cold instruments is likely to result in excessive bleeding
      increased post-operative morbidity and scar tissue. This case was treated with
      KTP/532 laser excision almost bloodlessly with practically no post-operative
      morbidity and unimimal scar tissue.

PMID- 23120131
TI  - Carotico-cavernous sinus fistula.
AB  - We present a rare case of carotico-cavernous sinus fistula who presented with
      proptosis with gradual diminision of vision following a roadside accident.
      Contrast enhanced CT scan and angiography confiruned the diagnosis and it was
      managed by transfemoral embolisation of right ICCF.

PMID- 23120132
TI  - Cervical thymic cyst-A case report.
AB  - A case of cervical thymic cyst in a five year old girl is reported. It was found
      to be extending between the greatvessels of the neck towards the pharynx. This
      type of presentation is rare which prompted us to document this case.

PMID- 23120133
TI  - Routine nasal packing follwoing nasal surgery-Is it necessary?
AB  - The practice of routine nasal packing after nasal surgery is usually customary
      and not evidence based. Post operative complications, while uncoumon, are
      sometimes pack related. A retrospective analysis of 110 patients who underwent a
      variety of nasal operations was performed to determine the incidence of
      complications when nasal packs were not routinely inserted 9 cases (8.2%) [6 out
      of these were revision surgeries] needed nasal packing for haemostasis at the end
      of surgery. 4 cases (3.6%) required to be packed in the immediate post operative
      period. One patient who required nasal packing developed a unilateral adhesion.
      No patient developed septal hematoma. The need for routine nasal packing is not
      supported. Packing should be indicated where there continuous bleeding at.

PMID- 23120134
TI  - Endoscopic KTP-532 laser assisted diverticulotomy for Zenker's diverticulum.
AB  - Zenker's diverticulum, though counnon in western countries is uncommon in India.
      This diverticuham is an extension of umcosa through Killian's dehiscence. Various
      surgical methods have been described for the treatment of this condition
      including the use of lasers but none in Indian Journals. In this paper we
      describe a case of Zenker's diverticulum where diverticulotomy using KTP532 laser
      was successfully performed. Its advantages over other techniques are mentioned.

PMID- 23120135
TI  - Surgical management of bilateral abductor paralysis by extralaryngeal approach.
AB  - Paralysis of the abductors of both vocal cords causes the vocal cords to lie in
      the midline or paramedian position. This compromises the airways and causes
      respiratory distress which may often be acute necessitating tracheostomy. A
      lateralisation of the vocal cord is required to provide adequate airway without
      significantly affecting speech. Extralaryngeal approach is our preferred
      approach. This article reports a study of eight cases who underwent arytenoid
      abduction by an extralaryngeal approach for bilateral abductor paralysis of vocal
      cords.

PMID- 23120136
TI  - Midline cervical cleft: A report of two cases.
AB  - Congenital midline cervical cleft is a rare congenital anomaly. The cardinal
      diagnostic features are-(1). Fistula's opening are located caudally (2)
      Internuittent serous fluid discharge in the early neonatal period (3). Nipple
      like appearance of the cleft in the superior aspect (4). Widened scar and
      mininual neck contracture in later life. Two such cases are reported herewith
      with briefreview of literature and it's surgical management.

PMID- 23120137
TI  - Hydatid cyst of thyroid: An unusual cause of stridor.
AB  - A rare case of hydatid cyst of the thyroid is reported, which presented with slow
      growing swelling of weck in thyroid region since two years and severe dyspmoea
      and stridor since S days. She was posted for emergency tracheostomy with
      provisional diagnosis of multimodular thyroid goitre. During surgery multiple
      hydatid cysts in left lobe of thyroid were found and all cysts were removed.
      Dyspnoea and stridor were relieved post-operatively. Pre-operative diagnosis of
      this condition is difficult; diagnosis is usually made at the time of Surgery.

PMID- 23120138
TI  - Primary tuberculosis of parotid gland.
AB  - A young female presented with complaint of swelling of the parotid region for one
      year. She was diagnosed as a case of primary tubercular parotiditis. The
      diagnosis was confirmed by fine needle aspiration cytology. She was managed with
      antitubercular drugs. After completing the course the swelling resolved
      completely and there was no recurrence.

PMID- 23120139
TI  - Current trends in electronic larynges.

PMID- 23120140
TI  - Choanal atresia: Experience with transnasal endoscopic technique.
AB  - Congenital choanal atresia has been recognized for over 200 years, first
      described by Roederer in 1775 (Lantz and Brick, Laryngoscope 91, 1981, 1626.
      Samuel and Fernandes. Laryngoscope 95, 1985, 326). This condition is unconunon,
      occurring in approximately 1 in 7000 live births. Unfortunately, a single ideal
      procedure for this condition does not exist. Stankiewicz is credited with the
      first description of endoscopic techniques for choanal atresia repair. All
      patients diagnosed to have choanal atresia treated between 1999 and 2000 were
      reviewed. Out of four patients two underwent endoscopic repair. This article
      attempts to address this controversy between endoscopic and traditional
      approaches to neonatal choanal atresia.

PMID- 23120141
TI  - Oral submucous fibrosis-New dimensions in surgery.
AB  - The oral submucous fibrosis (OSMF) has been managed earlier by various medical
      and surgical modalities but none of these methods is found to give relief to
      these patients. Hence, a new method has been developed by us. Patients, who
      reported with pallor of the palate cheek, oropharyn and the tonsils, due to the
      fibrosis, leading on to mild, moderate to severe trismus, were given a good long
      term rehef by this surgical method. This study involved 60 patients between 1979
      and 2000 with a female-to-male ratio of 1?3 with age ranging from 13 to 60 years
      suffering from the disease. The surgical method adopted in these cases used a
      single staged rotation tongue pedicle flap on either side from the dorsum of the
      tongue sutured to the raw area in the cheek without morbidity. In a 7-year follow
      up, we found the patients did not develop further fibrosis and the tongue flaps
      remained intact. The quality of life improved considerably and buccal mucosa is
      pink throughout the follow-up period. The modalities of treatment adopted are
      varied. Many tried the retro molar excision of the bands, which did not give long
      term results. Others used excision of the whole fibrotic area with skin grafting,
      which also failed. Some have tried muscle pedicle flap from outside with
      postoperative morbidity and failure. Some surgeons have tried fat grafts in the
      cheek region (Yeh, Int J Oral Maxillo facial Surg 1996; 25; 130). The experience
      of the others who used versatile, vascular tongue flaps in the oral cavity after
      cancer clearance, prompted us to attempt this new technique in the present series
      with gratifying results. This is a break through in the surgical management of
      OSMF, where other treatment modalities failed.

PMID- 23120142
TI  - Survival patterns in treated cases of carcinoma larynx in North India: A 10-year
      follow-up study.
AB  - Carcinoma of larynx is a common disease in North Indian population. It is seen
      commonly in smokers and alcoholics. It poses a serious health problem due to its
      tendency to cause airway obstruction and to make the patient aphonic if total
      larynxgectomy is done for curing this cancer. We conducted a retrospective
      analysis in 690 cases of carcinoma larynx presenting to Nehru Hospital,
      Postgraduate Institute of Medical Education and Research, Chandigarh. Various
      aspects of this disease like predisposing factors, patterns of spread,
      histological types, various treatment modalities, their complications and
      response of this disease to these therapeutic options were studied in detail.

PMID- 23120143
TI  - Radiological evaluation of chronic laryngotracheal stenosis.
AB  - Sixteen cases of chronic laryngotracheal stenosis were assessed. They underwent
      complete ENT evaluation including indirect laryngoscopy, direct laryngoscopy,
      microlaryngoscopy and tracheoscopy. Preoperatively plain X-ray of soft tissue
      neck and computed tomography (CT) was done. Good correlation was seen between the
      endoscopic assessment of the stenotic segment and the CT finding.

PMID- 23120144
TI  - Incidence of uncomplained secretory otitis media in patients undergoing
      adenotonswlectomy.
AB  - Secretory otitis media (SOM) is a pathologic condition of the middle ear in which
      an effusion is present behind an intact eardrum without signs of acute
      inflammation. This prospective study was conducted during the period of February
      1998 to January 2000. One hundred children of age group 2-12 years were followed
      up at intervals of 1, 2, 4, 12 weeks, 6 months and 1 year postoperatively. We
      carried out the established techniques of myringotomies and grommet insertion
      (shepherd type) to detect and resolve SOM. We found that the URTI was a prime
      factor as the cause for SOM. Myringotomy and grommet insertion results in drying
      up of fluid and return of normal hearing status in SOM.

PMID- 23120145
TI  - Intrathyroid injection of triamcinolone acetonide in thyroid swelling disorders.
AB  - Patients with thyroid swelling disorders, particularly females, are not happy
      with the postoperative scar on the neck after a thyroid surgery. Medical
      management can restore thyroid hormones to the normal levels but cannot reduce
      the swelling easily. Intrathyroid injection of triamcinolone acetonide, a
      nonsurgical procedure was tried in 76 cases of thyroid swelling disorders.
      Randomised cases of thyroid swelling disorders with the size less than 4 4cm were
      selected for this procedure. After excluding the cases associated with diabetes,
      adenoma, toxic state and malignancy, a course of three to ten sittings of
      intrathyroid injections was administered in each selected patient. Patients with
      abnormal thyroid functions were treated to the enthyroid state before the
      therapy. About 90% had excellent results, 5% fair results and 4% poor results.
      Intrathyroid injection of triamcinolone acetonide is found to be a satisfactory
      modality of treatment for thyroid swelling disorders and found to be acceptable
      to the patients as well.

PMID- 23120146
TI  - Clinico bacteriological evaluation of surface and core microflora in chronic
      tonsillitis.
AB  - The present study is undertaken on 50 tonsillectomy cases to determine the
      correlation between surface culture swabs and tonsillar core. Tonsillar disease
      may stem from the bacteria within the core of the tonsil, rather than the
      bacteria identified on its surface. Also no consistent pattern of combinations of
      different pathogenic bacteria was noted. The study proves that surface culture
      does not reliably predict core pathogens.

PMID- 23120147
TI  - Rhinocerebral mucormycosis: An analysis of probable mode of spread and its
      implication in an early diagnosis and treatment.
AB  - The study was done in two parts:Analysis of CT scan findings of 17 cases of
      mucormycosis to determine paranasal sinus, orbital and intra-cranial
      involvement.Cadaveric dissections of the ethmoid complex anatomy to correlate the
      probable mode of spread. Ethmoidal sinus was found to be the most commonly
      involved. The disease probably appears first here, spreads to orbit through the
      lamina papyracea and then through the retro-orbital region, intra-cranially. Our
      aim would be to diagnose the disease at the stage of ethmoid involvement. In
      immuno-compromised patients, if headache, peri- or retro-orbital pain or blood
      stained nasal discharge occur; a CT scan of the paranasal sinuses and a nasal
      endoscopy with biopsy from anterior ethmoids, if this area shows pathology then
      CT scan must be performed. If this is positive for mucormycosis, surgical
      debridement of the involved sinuses is to be done and Amphotericin B as intra
      venous infusion and treatment of underlying condition is started.

PMID- 23120148
TI  - Epistaxis: A retrospective clinical study.
AB  - Epistaxis is a common otolaryngologic problem. A 2.5 years retrospective study
      (June 1998 December 2000) of patients attending outdoor or indoor services of
      Department of ENT with complaint of nasal bleeding was done. The study was
      conducted on 88 patients for the incidence, age and sex relation, etiological
      factors, clinical findings, and treatment methods for epistaxis.

PMID- 23120149
TI  - Intracranial complications of otitis media: In retrospect.
AB  - OBJECTIVE: Evaluating intracranial complications of otitis media. DESIGN: An
      Evaluative study of 106 cases of intracranial complications secondary to otitis
      media. INTERVENTION: Diagnosis is based on history, clinical exam (general,
      systemic and ENT), investigations hemogram, X-ray mastoid CT scan brain and
      mastoid. TREATMENT: Medical management:IV Higher Antibiotics.Surgery for
      complicating pathology:Pus (in Abscesses)-bram canula aspiration.Lateral sinus
      thrombosis (thrombus removal),Otitic hydrocephalus (epidural
      catheterization).Primary disease eradication:Exploration of mastoid. RESULTS:
      Fully recovered patients without residual neurodeficit (85%), Morbidity (6%) CSF
      otorrhoea secondary to otitic hydrocephalus (9%) Mortality: preoperative (3%) and
      postoperative (6%). CONCLUSION: Otological approaches for management of cases of
      intracranial complications of otitis media are equally comparable with results by
      neurosurgical approaches of management. Therefore, holding promise if applied in
      the rural and peripheral parts of India with limited resources even with absence
      of the expertise of Neurosurgical Department.

PMID- 23120150
TI  - Mucormycosis: A retrospective study.
AB  - A retrospective study has been carried out in a hospital over the past 5 years on
      13 patients of mucormycosis. The study included evaluating the etiology,
      pathology, clinical features, management, and complications of mucormycosis. The
      results and conclusions have been studied and summarised in our paper.

PMID- 23120151
TI  - Isolated uvulitis: An uncommon but not a rare clinical entity.
AB  - Infections of uvula have been described in association with group A streptococcal
      pharyngitis (Rapkin, JAMI, 43, 1980, 1843), or Haemolytic influenzae type b
      epiglottitis. Medicine (Gorjinkel HJ, 58, 1979, 80) however, to our knowledge,
      only two cases of isolated uvulitis are reported in world literature. We report
      five cases of isolated uvulitis in adults.

PMID- 23120152
TI  - Tracheal agenesis.
AB  - Tracheal agenesis, though seemingly rare and fatal to date, has been reported
      with increasing frequency. Establishment of the diagnosis necessitates a high
      index of suspicion in an infant in respiratory distress an birth, without a cry
      and in whom intubation is difficult. We report a case of tracheal agenesis.

PMID- 23120153
TI  - Virtual bronchoscopy: Our early experience.
AB  - Virtual bronchoscopy is one of the many new radiological scanning techniques that
      have been recently introduced. Virtual endoscopy, according to Ahlquist (Ahlquist
      and Johnson CD, Gastroenterology, 112, 1997, 2150) is a technique for visualizing
      interior cavities using computer graphic techniques. Virtual bronchoscopy
      generates 3D reconstructions of the human airway from high-resolution CT data
      sets of the chest and performs a simulated bronchoscopy. This method uses
      perspective surface or volume rendering to produce endoscope-like visualizations
      of the airway. Our early experience with this new investigative modality in cases
      of laryngeal and subglottic stenosis and intratracheal tumors is discussed.

PMID- 23120154
TI  - An impacted meat bone in the larynx with an unusual presentation.
AB  - Lodgment of foreign bodies in the aero-digestive tract commonly occurs in the
      infant and children (Hazra et al, Indian J Otolaryngol Head Neck Surg
      1993;2:216). Children especially between 1 and 3 years appear to be more
      vulnerable (Aylec et al, J Thoracic Cardiovascular Surg 1977;74:145). Ninety
      percent of these foreign bodies are accidental in nature and are due to
      carelessness and are avoidable (Holinger and Holinger. Chest 1978;73:721).
      Lodgment of foreign body has been usually seen to occur in mentally retarded
      intoxicated, or edentulous adult and to some other persons like fishermen.
      electrician, and decoration worker who use to hold those materials in between
      their teeth during their work. Usually, the victims present with respiratory
      distress. hoarseness of voice and/or dysphagia, which are proceeded by a severe
      history of choking cough immediately after ingestion of foreign bodies. Heroic
      attempts of removal of the foreign bodies may be dangerous to life. Therefore,
      each case should be dealt with proper care and precautionary measures. Here we
      present a case of an impacted meat bone in the larynx with the only complaint of
      hoarseness of voice for 2 weeks.

PMID- 23120155
TI  - Foriegn body oesophagus: A case report.
AB  - We are reporting this case because of the age of the patient, and unawareness of
      the parents, as 20-day-old child cannot eat an FB of its own:

PMID- 23120156
TI  - Immediate toxic effects of methyl iso cyanate on human ear, nose and throat.
AB  - Methyl Iso Cyanate (MIC) is one of the most toxic chemicals known to man. In
      December 1984, a large amount of this lethal gas leaked from the Union Carbide
      Factory situated in Bhopal (Madhya Pradesh, India). There were many casualties
      and, damage to the vital organs of the body. To date, there has been no study in
      the field of Otolaryngology till now. This paper presents three cases, where ear
      nose and throat affliction was detected in the inmediate period (4S h) of
      exposure to MIC. Most of the effects were temporary and involved a cranial nerve.
      There was a complete recovery without any surgical intervention.

PMID- 23120157
TI  - Enterobius vermicularis in the nose: A rare entity.
AB  - A rare case of enterobius vermicularis pin-worm is reported in the nose. An 11
      year-old girl presented with the vague symptoms of crawling sensation in the nose
      for few weeks, who had received treatment for allergic rhinitis. The nasal
      secretions were examined and confirmed the diagnosis of pinworm infection and
      treated by albendazole.

PMID- 23120158
TI  - CT cisternography in cerebrospinal fluid rhinorrhea: Could it have a therapeutic
      role?
AB  - Two cases of spontaneous cessation of cerebrospinal fluid (CSF) rhinorrhea
      following iohexol computerized tomographic (CT) cisternography are presented.
      This report contradicts the current thinking about conservative treatment in CSF
      rhinorrhea. We propose that iohexol CT cisternography may have a therapeutic role
      in the management of spontaneous CSF rhinorrhea.

PMID- 23120159
TI  - A sterile acute retropharyngeal abscess.
AB  - A 12-year-old male admitted to ENT ward on an emergency basis with history of
      foreign body in throat. It came out along with induced vomiting, followed by
      fever, Odynophagia and restricted Neck movements. It is proved as a case of acute
      retropharyngeal abscess. But it turned out to be the sterile abscess, which is
      rare and new thing for us. Hence presented herewith-brief review of literature.

PMID- 23120160
TI  - An unusual complication of intranasal antrostomi.
AB  - Intranasal antrostomies are performed for treating maxillary simusitis. Here we
      present a rare case, who developed maxillary simusitis as a complication of the
      previous inferior meatal intranasal antrostomy. This case also proves the current
      concept that even though the inferior meatal antrostomy opening may be patent,
      the drainage is through the natural ostium.

PMID- 23120161
TI  - Rare andunusual presentation of multiple oesophageal foreign bodies in infant.
AB  - Children and aged are the most commonly affected persons with foreign body in
      oesophagus. The case of oesophageal foreign body reported here is unique as the
      male infant remained undiagnosed for more than 12 days and presented without any
      history of swallowing of foreign body and or dysphagia. The other unusual
      features of this case were gradual increase in the number of oesophageal foreign
      bodies.

PMID- 23120162
TI  - Foreign body in bronchus: An unusual presentation.
AB  - Exogenous foreign bodies in the trachea bronchial tree are not uncomion
      particularly in children. Children who are not given proper individual attention
      at an early age are more hable to ingest or inhale foreign body.

PMID- 23120163
TI  - Growth retardation due to undiagnosed foreign body oesophagus.
AB  - Foreign body oesophagus, specially, coin is not very uncommon in children. But an
      undiagnosed old foreign body (coin) presented with growth retardation and
      swallowing in a peculiar posture, which has to be removed by thoracotomy-a case
      report.

PMID- 23120164
TI  - Pleomorphic adenoma of nasal septum.
AB  - The pleomorphic adenoma is the most common benign tumour of the major and minor
      salivary glands. We report a 40-year-old female patient, who presented with
      progressive swelling and deformity of the left side of her nose for last 2 years.
      On a lateral rhinotomy a mass (4 cm X3 cm in size) was found to be arising from
      the cartilaginous part of the nasal septum. The mass was emicleated from its
      capsule and the walls excised. The histopathological examination revealed it to
      be pleomorphic adenoma.

PMID- 23120165
TI  - An exrathoracic presentation of castleman's disease.
AB  - Castleman's disease, also known as angiofollicular hyperplasia, usually occurs in
      the mediastinum and rarely in cervical region as solitary mass.
      Histopathologically four variants have been recognized (Castleman et al. Cancer
      1954;9:822-30) hyaline vascular type-most common type (Keller et al. Cancer
      1972;29:670-83) plasma cell type (Salisbury, Pediatric Pathol 1990;10:609-15)
      transitional type (Shahidi, Mayo Clinic Proc 1995;70:969-77) stromal rich type.
      We report a case of Castleman's disease of typical histopathological picture of
      angio follicular hyperplasia arising from the right carotid triangle of neck in
      12-year-old child without any associated systemic illness.

PMID- 23120166
TI  - Pruritus ears: How do I manage it?

PMID- 23120167
TI  - A study of routine exposure of recurrent laryngeal nerve during thyroid surgery.
AB  - One of the main complications of thyroid surgery is injury to recurrent laryngeal
      nerve (RLN), which causes severe morbidity to the patient in postoperative
      period. To find out the incidence of RLN injury and its consequences, a
      prospective study was done in a group of 142 cases during the years 1999-2000.
      Different types of thyroidectomies for various diseases lbw of the thyroid gland,
      wherein a routine identification and exposure of the P-R was done through out its
      full course till its entry into the larynx at cricothyroid membrane. Three cases
      of temporary RLN injury were found and not a single case of permanent nerve
      injury was seen during our study. Three cases of nonre current LN were found on
      the right side of the gland. The temporary injury of the nerve completely
      recovered during 2-5 months of follow-up. We present some reviews of the
      literature to provide various authors, views and experiences regarding injury of
      RLN associated with thyroid urgery.

PMID- 23120168
TI  - Endoscopic laser excision in the management of laryngotracheal stenosis.
AB  - Sixteen cases of Chronic laryngotracheal stensis were included in the study. They
      underwent endoscopic CO(2) laser excision of the stenotic segment. Three patients
      were decannulated. giving a success rate of 18.75%.

PMID- 23120169
TI  - Clinical profile and serum beta-carotene levels in oral submucous fibrosis.
AB  - Clinical profile and serum beta-carotene levels in 100 cases of oral submucous
      fibrosis (OSMF) were studied. Prevalence of OSMF was noted to be 0.93% of new
      cases attending ENT OPD Age of cases varied from 12 to 78 years (mean 29.09
      years) with male-female ratio of 3.3:1 and 80% literacy. Students constituted the
      single largest group. Burning sensation in oral cavity and inability to open
      mouth were the chief complaints in 95% cases. In all cases changes in colour of
      buccal mucosa and palpable fibrous bands in oral cavity were present followed by
      trismus (99%). About 52% patients were in grade-III OSMF (Journal of Indian
      Dental Association, 49: 187), oral habits of chewing tobacco, betal nut, etc.
      were present in 95% patients. Excessive use of chillies was present in 60 and 74%
      patients were non-vegetarian. Serum beta-carotene levels were below normal in all
      the three grades of OSMF, lowest being in grade III.

PMID- 23120170
TI  - Balloon and bougie dilation of benign esophageal strictures.
AB  - The present study is undertaken on 50 tonsillectomy cases to determine the
      correlation between surface culture swabs and tonsillar core. Tonsillar disease
      may stem from the bacteria within the core of the tonsil, rather than the
      bacteria identified on its surface. Also no consistent pattern of combinations of
      different pathogenic bacteria was noted. The study proves that surface culture
      does not reliably predict core pathogens.

PMID- 23120171
TI  - Classification of nasal septal deviations-Relation to sinonasal pathology.
AB  - The relationship between sinonasal disease and septal deriations is well known,
      albeit vaguely. There was no serious attempt to classify deviations except
      calling them mild deviations, gross deviations, spur; high deviations, etc. The
      airflow changes in these deviations, which lead to mucosal changes predisposing
      to polyps or infection have not been documented clearly. In this study we made a
      classification of septal deformities by modifying the classification described by
      Mladina in 1987. This classification has been applied to 100 consecutive cases
      who have been advised nasal surgery and 100 normal individuals who did not have
      any nasal symptoms. All patients had CT scan of PNS and their CT findings were
      studied in relation to the type of deviation. This paper presents an analysis of
      the incidence of various types of deviations in patients and controls and the
      relationship of different deformities to the sinus pathology.

PMID- 23120172
TI  - Comparative study of percutaneous dilatational tracheostomy and conventional
      tracheostomy in the intensive care unit.
AB  - OBJECTIVE: Tracheostomy is a one of the earliest described surgical procedure
      dating back to 2000 B.C. Percutaneous tracheostomy is becoming increasingly
      popular as an alternative method for conventional tracheostomy in the intensive
      care unit. In this study we compare the results of the use of these 2 techniques
      in 32 patients who underwent elective tracheostomy in the intensive care unit.
      STUDY DESIGN: Prospective randomized comparative study. SETTING: Tertiary care
      hospital. PATIENTS: Adult intubated patients selected randomly in the intensive
      care unit with normal cervical soft tissue, laryngeal framework, palpable cricoid
      cartilage and normal coagulation parameters. RESULTS: 17 patients underwent
      conventional tracheostomy and 15 patients underwent percutaneous dilatational
      tracheostomy. Demographic data and duration of intubation comparable between two
      groups. The mean operative time, blood loss and complications were lower in
      percutaneous than in conventional tracheostomy. CONCLUSIONS: PDT is quicker to
      perform and has lower blood loss and complication rates compared to conventional
      tracheostomy. However percutaneous tracheostomy is not indicated in emergencies
      and in children. The cost of the percutaneous kit and use of bronchoscopy adds to
      the cost. It is a good alternative to conventional tracheostomy in properly
      selected patients.

PMID- 23120173
TI  - Proptosis through eyes of E.N.T. surgeon.
AB  - The study was conducted to get an overview of the various E.N.T. lesions
      presenting with proptosis. 50 cases were thoroughly investigated, treated
      according to the diagnosis and adequately followed up. Based on this data it can
      be concluded that most of the E.N.T. lesions presenting with proptosis are
      neoplastic in origin with other chief complaints being epistaxis and nasal
      obstruction CT scan is a must in the investigation of these conditions and USG of
      the orbits is an useful non-invasive investigation.

PMID- 23120174
TI  - Hearing benefit in middle ear reconstructive surgery: A comparative study of the
      current methods.
AB  - The objective of this prospective study was to compare two methods of predicting
      the level of hearing benefit following reconstructive middle ear surgery, namely
      Glasgow benefit plot and Belfast rule of thumb. The correlation of hearing
      benefit as measured by using these methods was also compared with patient's self
      assessment of his/her hearing status. Sixty patients undergoing middle ear
      reconstructive surgery were studied. Hearing status was assessed pre and post
      operatively by pure tone audiometry and self-assessment by patient with a
      questionnaire. The accuracy of predictability of hearing benefit by the two
      methods was compared with the patient's own assessment. Relevant literature on
      the subject is reviewed.

PMID- 23120175
TI  - Endoscopic sphenopalatine artery ligation for refractory posterior epistaxis.
AB  - Intractable posterior epistaxis remains a challenging problem for our specialty
      Conventional management options in the form of anterior and posterior packing,
      arterial ligation of the internal maxillary or the external carotid artery and
      embolization, are not entively satisfactory because of morbidity, high failure
      rates, and occasional significant complication. Our experience with endoscopic
      sphenopalatine artery ligation for four patients with posterior existaxis is
      described. All patients had epistaxis refractory to anterior and posterior nasal
      packing, which was rapidly controlled following the procedure. The technique of
      spheno-palatine artery ligation is described. The technique is simple and
      effective and prevents the morbidity and complications of nasal packing. It is
      especially useful in systemically compromised individuals who otherwise tolerate
      nasal packing poorly. and should be one of the treatment options to be considered
      relatively early in the management of epistaxis refractory to anterior &
      posterior nasal packing.

PMID- 23120176
TI  - Emergency Otorhinolaryngolocal cases in Medical College, Kolkata-A statistical
      analysis.
AB  - At the round the clock entergency of the Deparment of Otorhinolaryngology,
      Medical College, Kolkata, different types of cases are managed everyday. The
      various emergency conditions encountered by us in last four years are gathered
      and analyzed in this study. The different problems and their modes of management
      are discussed here.

PMID- 23120177
TI  - Study of the effects of chemotherapy on auditory function.
AB  - Chemotherapeutic agents are known to cause multiple toxicities such as
      myelotoxicity, nephrotoxicity and ototoxicity. A prospective study was carried
      out on 60 patients receiving Cisplatin based chemotherapy in a tertiary care
      centre. The effects of Cisplatin on auditory function were studied using
      metabolic, biochemical and audiological parameters. The auditory effects were
      correlated with the dose and duration of chemotherapy. The study concluded that a
      significant percentage (15%) of patients who were subjected to chemotherapy based
      on Cisplatin developed high frequency sensorineural hearing loss which was
      permanent and irreversible in nature.

PMID- 23120178
TI  - Pharyngo oesophageal strictures and its reconstruction by delto pectoral flaps.
AB  - Delto pectoral flap is a thin and pliable cutaneous axial flap suitable for the
      reconstruction of pharynx and upper oesophagus. Corrosive stricture of the
      pharyngo oesophageal area can very well be reconstructed by deltopectoral flap.
      Oesophageal reconstruction by viscera like stomach or colon often produces
      anastomic stricture at the upper anastomic site with hypopharynx or upper
      oesophagus. Delto pectoral flap can also be used to reconstruct this anastomotic
      stricture. Postoperative swallowing is satisfactory when reconstruction is done
      with this flap.

PMID- 23120179
TI  - Endoscopic septoplasty.
AB  - Endoscopic septoplasty is a minimally invasive technique that helps us to correct
      defornity of septum under excellent visualization. Lanza et al & Stammberger
      initially described the application of endoscopic technique for the correction of
      septal deformity in 1991. A retrospective study was carried out of all the cases
      that underwent endoscopic septoplasty at Dr. Shroff's Charity Eye hospital from
      March 1998 to March 2000. 78 consecutive septoplasty patients were identified in
      two years. Out of these 48 septoplasties (52%) were performed with endoscopic
      technique. A large percentage of cases 48(41%) were those where septoplasty was
      performed in conjunction with endoscopic dacro cysto rhinostomy. In 8 cases (16%)
      it was performed alone as a primary procedure, 4 deviations were broadly based
      deflections (12%), 10 of septal deformities were spurs (20%), in 4 cases more
      than one type septal deformities were encountered. Thus we feel that endoscopic
      septoplasty is a fast developing concept & gaining popularity with increasing
      trend towards sinus endoscopic surgeries. Furthermore in complex deformities,
      better correction is possible with the help of endoscope. Since we can clearly
      see the posterior deviations.

PMID- 23120180
TI  - Destructive aspergillosis.
AB  - The incidence of mycotic infections of paranasal sinuses is on the rise.
      Aspergillosis is the commonest fungal infection involving the nose and paranasal
      sinuses. This disease has a varied presentation ranging from the allergic form to
      the more deadly invasive or destructive form. Destructive fungal disease is
      almost regarded as synonymous with mucormycosis. The destructive potential of
      aspergillosis has not been highlighted in the medical literature. We here report
      a case of aspergillosis, which caused massive destruction of maxilla in an
      apparently healthy patient.

PMID- 23120181
TI  - Huge ameloblastoma of jaw-A case report.
AB  - Ameloblastoma is a tumor of odontogenic epithelium. It is a tumour of
      intermediate malignant potential which lies in the gray zone between benign and
      malignant neoplasm. A huge ameloblastoma revealing benign cytological features in
      FNAC is being reported.Ameloblastoma arises from odontogenic epithelium. This
      tumor can occur at any age. Though traditionally divided as solid and cystic,
      nearly all ameloblatomas show some cystic change. This tumor shows invasive
      property and a remarkable tendency of recurrence. The cases showing distant
      metastasis are recognized as malignant ameloblastoma. Ameloblastic carcinoma is a
      tumor with microscopic features of ameloblastoma that displays malignant features
      at cytological level.([2]) It usually has aggressive course. A case of large
      ameloblastoma with slow clinical course and benign cytological as well as
      histological features is being reported.

PMID- 23120182
TI  - Foreign body in the nasopharynx of a child.
AB  - Introduction of foreign body into the nasal cavity of the children by themselves
      is very common, but lodgment of foreign body in the nasopharyux following
      introduction through mouth is unusual. Here a case is presented from the
      Otorhinolaryngology department of S.S.K.M. Hospital, Kolkata, where a child was
      brought by their parents with history of introduction of a metallic foreign body
      in the mouth of the child by himself and this foreign body was found to be lodged
      in the nasopharynx of the child. The foreign body was removed orally in the out
      patient department. The patient returned home without any complication.

PMID- 23120183
TI  - Upper respiratory tract and cutaneous diphtheria.
AB  - With the global immunization programme of children there is a progressive decline
      in the number of diphtheria cases. It is a disease commonly affecting the
      children caused by Corynebacterium diphtheriae usually affecting the mucous
      membrane of the nose, pharynx or larynx. Cutaneous diphtheria is a rare entity.
      We present a rare case of cutaneous diphtheria in a 15-year-old boy with nasal
      pharyngeal and laryngeal involvement. The patient developed anaphylactic reaction
      to antidiphtheritic serum (ADS) during treatment, all of which were managed
      successfully.

PMID- 23120185
TI  - Bilateral lesions in brain in a young patient presenting as tinnitus and hearing
      loss.

PMID- 23120184
TI  - Ectopic thyroid: A rare cause of tracheal obstruction.
AB  - The endoluminal presence of thyroid tissue in the trachea is a rare cause of
      airway obstruction. Only 14 well documented cases of intratracheal ectopic
      thyroid tissue have been reported in English Literature since 1966. These lesions
      are mostly benign and nearly all patients present with symptoms of respiratory
      obstruction. We present a case of ectopic thyroid in cervical trachea presenting
      with symptoms of airway obstruction. Thorough clinical examination and
      investigations were carried out. A right hemithyroidectomy and excision of a part
      of the tracheal wall through a tracheotomy was performed for removal of the
      ectopic thyroid tissue from trachea. The clinicians & radiologists must be aware
      of this entity to avoid mistaking it for evidence of invasion by a malignant
      neoplas, and hence this report.

PMID- 23120186
TI  - Primary Non-Hodgkin's Lymphoma of the thyroid with lymphocytic thyroiditis.
AB  - Primary Lymphoma of the thyroid is one of the very rare entities accounting to
      less than 2% of thyroid malignancies. We present a case of primary Non-Hodgkin's
      Lymphoma of the thyroid with lymphocytic thyroiditis in a 60 year old woman. The
      patient presented with a rapidly growing nodular mass in the thyroid. The
      histological and immune marker features of the tumour were consistent with
      Primary Non-Hodgkin's Lymphoma of the thyroid with associated thyroiditis.

PMID- 23120187
TI  - Post traumatic laryngeal incompetence.
AB  - Self-inflicted laryngeal injuries are rare. This is a case of attempted suicide
      with a knife. The patient was brought into A&E and initial attempts at repair of
      the laryngo-skeletal structures were performed Later it became evident that the
      patient had an insensate hypofunctioning larynx. We present a technique aimed at
      rehabilitating the poorly functioning, incompetent larynx without the necessity
      for a permanent tracheostomy or laryngectomy. A single surgical procedure
      combining a cricopharyngeal myotomy, an anterior hyoid suspension and vocal fold
      angmentations was performed in an attempt to avoid a laryngectomy in non
      malignant pathology. The long-term results of this surgery would need to be
      subjected to further evaluation.

PMID- 23120188
TI  - Civilian firearm injuries in head and neck.
AB  - Firearm injuries to the head and neck contribute to substantial medical,
      medicolegal, economic as well as social problems. Internal wounds in the head and
      neck by firearms are usually complicated and are diagnostically and
      therapeutically challenging cases. Based on four cases of non-fatal firearm
      injuries, we discuss problems related to firearm wounds, their irregular path,
      final lodgment of the bullet and their diagnostic and therapeutic consequences.
      In the present study it was observed that a fatal looking firearm injury can
      result in a favourable and interesting outcome.

PMID- 23120189
TI  - An unusual foreign body in the nasopharynx.
AB  - Coins, playing toys etc. are the commonest foreign bodies of food and air
      passages in children, but such an unusual and large size foreign body in
      nasopharynx is not very common. Due to structure of the bangle there was no
      alarming symptoms.

PMID- 23120190
TI  - Laryngopharyngeal reflux: Current opinion.
AB  - The increasing importance of LPR is being recognized day by day in ENT practice.
      LPR has a significant negative impact in the quality of lives of the patients.
      Although its impact is similar in some respects to that of laryngopharyngeal
      disease, LPR has a more significant impact on patient's social functioning and
      vitality.([23]) All ear, nose and throat practitioners need to be sensitised to
      the presence of LPR and the need for starting treatment wherever required. Lot of
      hitherto symptoms of unknown aetiology are being increasingly of treating
      patients with atypical reflux symptoms such as hoarseness (unexplained cause),
      globus, throat clearing, cough, etc., with antireflux therapy.([24]).

PMID- 23120191
TI  - Foresteir's Disease (dish) causing dysphonia and dysphagia.
AB  - A cardiac patient who under went bypass surgery, has been investigated for mild
      dyspahagia and Dysphonia. He has been diagnosed as a case of Foresteri's Disease
      and has been followed up for one year. The Symptoms and findings were stationary.

PMID- 23120192
TI  - My last issue as the editor.

PMID- 23120193
TI  - Endoscopic dacryocystorhinostomy vs KTP 532 laser-assisted endoscopic
      dacryocystorhinostomy.
AB  - OBJECTIVES: Advances in endoscopy and lasers have improved surgical management of
      chronic nasolacrimal duct obstruction. This is a preliminary comparison between
      standard and laser assisted endoscopic dacryocystorhinostomy (DCR). STUDY DESIGN:
      Combined retrospective and prospective study. SETTING: Tertiary referral
      hospital. PATIENTS AND METHODS: Thirty-eight cases of chronic nasolacrimal duct
      obstruction underwent endoscopic DCR (26 standard and 12, laser-assisted) and
      were assessed at 3 and at 6 months postoperatively by nasal endoscopy. RESULTS:
      Three months postoperatively (n=38), total relief of epiphora among the nonlaser
      group was 80.76 vs 75% in the laser group (P=0.982). At 6 months (n=19), the
      laser group had recorded 100% symptomatic relief compared to 85.71% in the
      nonlaser group (P=0.964). The laser group suffered fewer complications (33.33 vs
      46.15% for nonlaser group). CONCLUSION: Lasers show promise in long-term
      management of duct obstruction and are associated with fewer complications. A
      larger study is required before and generalization is made.

PMID- 23120194
TI  - Pneumatization correlated to myringoplasty and tubal function.
AB  - The prognostic significance of the size of mastoid air cell system in the results
      of myringoplasty has been a matter of debate. Fifty ears with dry central
      perforation following C.S.O.M. were investigated. The size of mastoid air cell
      system was determined with planimetry of the X-ray picture and eustachian tube
      function was assessed using flourescein dye and nasal endoscopy. Myringoplasty
      was performed in all the 50 ears and postoperative results in terms of graft take
      up and hearing gain were assessed. The correlation between the size of mastoid
      air cell system, results of myringoplasty and tubal function has been discussed.
      The results show no correlation between the size of mastoid air cell system,
      postoperative results of myringoplasty and eustachian tube function.

PMID- 23120195
TI  - The effect of bismuth subgallate as haemostatic agent in tonsillectomy.
AB  - Tonsillectomy is one of the frequent operations performed by Otolaryngologists
      world over: Otolaryngologists are in search of a technique of tonsillectomy where
      the operation time and operative blood loss is less. This study was carried out
      to evaluate the effect of bismuth subgallate (BSG) and adrenaline on
      tonsillectomy time blood loss during the surgery as well as on the number of ties
      used. A prospective randomized trial of 60 patients was carried out, in which 30
      had a tonsillectomy performed using BSG as haemostatic agent and in the remaining
      no heamostatic agent was used. Application of BSG in the tonsillar fossae reduces
      the operation time by 31.49%, the operative blood loss by 33.28% and also reduces
      the number of ties used by 53.33%. All these results are statistically
      significant.

PMID- 23120196
TI  - KTP Laser assisted microendoscopic cricopharyngeal myotomy and web excision for
      dysphagia management.
AB  - Cricopharyngeal dysfunction is defined as the delayed or incomplete relaxation of
      the cricopharyngeal muscle during swallowing. This may cause dysphagia and
      aspiration, affecting the quality of life. For this condition, injection of
      botulinum toxin into the cricopharyngeus, dilatation of cricopharynx with bougies
      and external cricopharyngeal myotomy have been the treatment of choice with
      varying results. We present in this paper the treatment of this clinical
      condition by KTP 532 laser a recent advance in the field of Otolaryngology and
      Head and Neck Surgery. Very few series have been reported in literature so far
      regarding the use of laser for cricopharyngeal myotomy. This is perhaps the first
      series of eight cases of KTP laser assisted microendoscopic cricopharyngeal
      myotomy and web excision reporting the benefit of this treatment by an Indian
      author in an Indian Journal. KTP laser assisted cricopharyngeal myotomy avoids an
      external scar; aids precise incision at the cricopharynx by direct visualization,
      brings optimum results in deglutition and reduces postoperative morbidity and
      complications. The short hospital stay reduces the overall cost. The use of KTP
      532 laser in the treatment of selected cases with cricopharyngeal dysfunction is
      therefore safe and effective.

PMID- 23120197
TI  - A safe and reliable technique in the management of preauricular sinus.
AB  - Preauricular sinus/pit is a common congenital malformation, which presents as a
      pit or depression at the anterior margin of the ascending margin of helix,
      adjacent to helicine crux, or adjacent to the tragus. It is inherited as an
      autosomal dominant incomplete pattern with variable power of expression. It is
      due to a defect in the auricular embyrogenesis, which results in the preauricular
      sinus or pit. It is closely related to the helical cartilage. Using local
      anaesthesia in adults an elliptical incision is made around the sinus, and
      extended to the postauricular area. Plane of temporalis fascia identified, skin
      anterior to the sinus is separated from the underlying soft tissue. The soft
      tissue between the plane of temporalis fascia and the skin anterior to the sinus
      is excised along with a piece of adjoining helical cartilage. With this method no
      recurrences were encountered.

PMID- 23120198
TI  - Cerebrospinal fluid rhinorrhoea-Transnasal endoscopic repair.
AB  - The recent advances in nasal endoscopic surgery in anterior skull base area have
      made it the procedure of choice for repair of cerebrospinal fluid rhinorrhoea
      (CSFR). The aim of the present study is to analyze the technique and efficacy of
      endoscopic repair of CSFR.

PMID- 23120199
TI  - KTP-532 laser in the management of rhinosporidiosis.
AB  - Rhinosporidiosis, a difficult granulomatous disease of the nose is notorious for
      its high rate of recurrence and vascularity. Potassium Titanyl Phosphate (KTP)
      laserization of the mass seems to have provided an optimal solution in the
      management of this disease. We present our experience with the use of KTP-532
      laser for this challenging disease.

PMID- 23120200
TI  - Endoscopic sphenopalatine artery ligation for refractory posterior epistaxis.
AB  - Intractable posterior epistaxis remains a challenging problem for our specialty.
      Conventional management options in the form of anterior and posterior packing,
      arterial ligation of the internal maxillary or the external carotid artery and
      embolization, are not entirely satisfactory because of morbidity, high failure
      rates and occasional significant complication. Our experience with endoscopic
      sphenopalatine artery ligation for four patients with posterior epistaxis is
      described. All patients had epistaxis refractory to anterior and posterior nasal
      packing, which was rapidly controlled following the procedure. The technique of
      spheno-palatine artery ligation is described.The technique is simple and
      effective and prevents the morbidity and complications of nasal packing. It is
      especially useful in systemically compromised individuals who otherwise tolerate
      nasal packing poorly. and should be one of the treatment options to be considered
      relatively early in the management of epistaxis refractory to anterior and
      posterior nasal packing.

PMID- 23120201
TI  - Deviated nasal septum in the newborn-A 1-year study.
AB  - A prospective study of 200 newborn babies was done at Silchar Medical College
      Hospital from September 2002 to August 2003. The babies aged from 0 to 4 days
      were taken in the study. They were examined for any signs of nasal obstruction,
      birth trauma, prolonged labour, mode of delivery (forceps/vaginal/caeserian
      section), intrauterine malposition, postmaturity, birthweight, cephalopelvic
      disproportion, parity of the mother and gestational period. The diagnosis was
      done by clinical examination, rhinometry, struts and applying cotton wool. In the
      study, the incidence was found to be 14.5% (29 cases). It was found that high
      birth weight babies, delivered by vaginal route (55%), to a primi mother are more
      likely to have DNS after birth. Moreover, intrauterine malposition particularly
      breech (45%) and prolonged labour seemed to play a role in newborn DNS. More
      importantly, the present study seems to indicate that since a good percentage of
      such deformity originate at the gestational period, early detection at the
      neonatal age is vital to manage and also to prevent complications and sequelae in
      adult life. Therefore, a policy of routine screening in view of early correction
      is advocated to decrease the morbidity associated with nasal septal deviation in
      newborns.

PMID- 23120202
TI  - Comparative study of endoscopic aided septoplasty and traditional septoplasty in
      posterior nasal septal deviations.
AB  - Patients with deviated nasal septum are advised surgery, which has seen several
      modifications since its inception. This recent technique of using nasal
      endoscopes gives better illumination and access to posterior septal deviations.
      The aim of the study was to identify the nasal septal pathology in relation to
      lateral nasal wall in a precise way and to correct this with minimal exposure,
      limited manipulation and least resection. Twenty five patients underwent
      endoscope aided and 25 conventional septoplasty. Results were graded on
      subjective and objective improvement. Endoscopic aided septoplasty (Otolaryngol
      Head Neck Surg, 1999; 120, 678; Laryngoscope 1994, 104, 1507; J Laryngol Otol
      1998, 112, 934; Ear Nose Throat J 1997, 76, 622) was found to be safe, effective
      and conservative approach with better patient compliance, shorter recovery time
      and greater stability of remaining septum.

PMID- 23120203
TI  - Evaluation of results of radiotherapy alone vs combined surgery and postoperative
      radiotherapy in carcinoma external auditory canal-10 years review.
AB  - Forty-one patients of external auditory canal (EAC) cancer attended the
      Department of Radiotherapy (RT), Medical College Hospital, Kolkata during the
      period from 1987 to 1996. Majority were above 50 years of age with slight female
      preponderance. Out of 41 patients 36 patients completed the full course of
      treatment of which 12 patients underwent combined modality treatment (RT 50-55 Gy
      plus surgery) and 24 patients received primary RT alone (55-60 Gy). Radiation
      therapy was given in standard fractionation schedule. Retrospective analysis
      revealed complete response in 8/12 (66.7%) in combined modality treatment group
      and in 3/24 (12.5%) in RT alone group. The actuarial 2 year survival was 19%.
      following RT alone, 85% following combined modality, 70% in early lesions and 18%
      in advanced lesions. The study suggests, surgical resection followed by
      postoperative irradiation is an effective method and better treatment option than
      RT alone as primary treatment modality for carcinoma of EAC.

PMID- 23120204
TI  - Epley's canalith-repositioning manoeuvre for benign paroxysmal positional
      vertigo.
AB  - The efficacy of the Epley's canalith-repositioning manoeuvre in the treatment of
      BPPV was assessed in this prospective study of 62 patients. Patients were
      selected based on symptoms of positional vertigo and positive Dix-Hallpike's
      positional test. Patients were divided into two groups; first group comprising 34
      patients underwent Epley's manoeuvre alone where as the other group comprising 28
      patients underwent Epley's manoeuvre along with mastoid oscillator. At the end of
      1 month patients were assessed subjectively by visual analogue scale (VAS) and
      objectively by Dix-Hallpike's positional test. On VAS, 85.7% patients had
      complete resolution of symptoms of BPPV in both the groups. Objectively 88.2% did
      not have positional nysfagmus after 1 month in first group whereas in the second
      group 86% had complete response at the end of 1 month of therapy. Follow up of 6
      months could be done in 38 patients, out of which 7 (18.4%) had recurrence of
      their symptom of vertigo and positive Dix-Hallpike's positional test, whereas one
      patient continued to have no relief by Epley's manoeuvre. There was no difference
      in subjective and objective parameters even when CRP was performed using mastoid
      vibrator.

PMID- 23120205
TI  - The complete branchial fistula: A case report.
AB  - The incomplete branchial fistula is not an uncommon congenital anomaly of
      branchial apparatus but a complete one is rare. Here we report a case of complete
      congenital branchial fistula with an internal opening near the tonsillar fossa.

PMID- 23120206
TI  - Case of foreign body in Wharton's ductcausing silolithiasis.
AB  - A case of swelling of submandibular gland in a 20-year-old male is reported. This
      eventually proved to be caused by a foreign body-thorn in the Wharton's duct.

PMID- 23120207
TI  - Winkler's disease.
AB  - Winkler's disease otherwise known as chondrodermatitis nodularis chronica helices
      (CNHC) is characterized by a painful persistent erythematous nodule, mostly
      located at the rim of helix of pinna. Occurs mostly in men over 40 years of age.
      Standard therapy is by local excision or carbon dioxide laser vaporization.
      Recurrence is frequent.

PMID- 23120208
TI  - Giant cell reparative granuloma of posterior ethmoid: A case report.
AB  - Giant cell reparative granuloma (GCRG) is an unusual, nonneoplastic fibrous
      lesion affecting maxillary and mandibular bones and only rarely, the cranial
      bones. Giant cell reparative granuloma of the posterior ethmoid is exceedingly
      rare. To the best of our knowledge none of such case has been previously
      reported. Being a soft fleshy lesion of bone, if tends to have a benign course,
      not aggressive, it often recurs following incomplete excision. We report the case
      of a woman with a GCRG of right posterior ethmoid. We discuss the clinical
      picture, differential diagnosis, histologic evaluation and appearance on computed
      tomography.

PMID- 23120209
TI  - Cochlear implantation in ossified cochlea-Merf experience.
AB  - Labyrinthitis Ossificans is a sequelae secondary to meningitis wherein
      ossification of the cochlea may be partial or complete. Among four of our
      patients who underwent cochlear implantation, two patients required double array
      insertion while the other two had a partial insertion of straight array
      electrodes. Despite partial insertion of electrodes, no significant differences
      in auditory benefit was noted&matched the peers who had complete insertion.

PMID- 23120210
TI  - Profile of neck cellulitis-Clinician's dilemma.
AB  - Cellulitis neck may be the only presenting feature of an underlying disease in
      the upper aerodigestive tract. Inflammation in the head and neck region spreads
      through potential neck spaces to the surface by direct extension or by lymphatic
      spread. Four cases of cellulitis neck who presented in the emergency department
      and progressed with variable clinical course are reported in this paper. After
      initial treatment with parenteral broad spectrum antibiotics, investigations
      revealed underlying disease and appropriate treatment was instituted. The
      importance of detailed clinical examination, investigations and key management
      protocols are highlighted.

PMID- 23120211
TI  - Lymphangioma tonsil-Rare case study.
AB  - Eight year-old boy reported to ENT, OPD with a large swelling in the oral cavity
      arising from his left tonsil. The mass was excised by transoral approach and
      histopathological examination proved to be a case of lymphangioma tonsil. This
      case is reported for its rarity.

PMID- 23120212
TI  - An overlooked bronchial foreign body in adult.
AB  - A long-standing undiagnosed foreign body in bronchus in adult is very rare case.
      A 42 years old man with complain of chronic cough with expectoration and fever
      since 3 years was treated medically including a complete course of AKT for 6
      months without improvement in the patient's condition. On taking detailed
      history, it was revealed that patient had swallowed or aspirated a denture before
      3 years, which was overlooked by the treating clinicians. As denture is
      radiolucent foreign body it remained undiagnosed in X-ray chest for 3 years. It
      was visualized on flexible bronchoscopy and removed with rigid bronchoscopy. The
      patient got relieved from symptoms within a week. So presence of chronic cough.
      wheezing and fever without reduced air entry and without obstructive finding in X
      ray chest, should indicate the need for diagnostic bronchoscopy. Also adult
      patients of recurrent lower respiratory symptoms in spite of satisfactory medical
      treatment must be submitted for diagnostic bronchoscopy.

PMID- 23120213
TI  - Tuberculosis of temporomandibular joint.
AB  - Tuberculosis of the temporomandibular joint is a very rare disease. Its close
      relation to the parotid can cause diagnostic confusion. This case is being
      reported keeping this point in view.

PMID- 23120214
TI  - An unusual case of congenital choleasteatoma in the mastoid with epidural abscess
      and cutaneous fistula.
AB  - A unique case of congenital choleasteatoma within the mastoid region of the
      temporal bone is described. The patient presented with a cutane ous fistula into
      the external auditory canal and epidural abscess. The clinical, radiological,
      histopathological and operative findings are discussed. A review of the
      literature shows only one report of a similar case.

PMID- 23120215
TI  - Endoscopic removal of malignant melanoma of the nasal cavity.
AB  - Mucosal melanoma of the nasal cavity is a rare tumour. With the extended used of
      nasal endoscopes and advent of CT scan, early diagnosis of nasal melanoma and
      accurate assessment of its extent is possible. This allows endoscopic excision of
      tumour, avoiding unnecessary removal of healthy tissue. Here we present a case
      where endonasal endoscopic excision with postoperative radiotherapy achieved
      disease free survival till follow up (nearly 2 years).

PMID- 23120216
TI  - Choristoma of the tonsil.
AB  - A 13 year old female patient presented to ENT OPD with chronic recurrent
      tonsillitis and underwent tonsillectomy. The histopathological examination
      revealed heterotopic cartilage in both the tonsils. The postoperative period was
      uneventful. The histopathologic finding of choristom of the tonsil is rare.

PMID- 23120217
TI  - Unilateral choanal atresia: Presentation in adults.
AB  - Unilateral choanal atresia usually presents later in life than the bilateral one
      and may present in adults. We discuss three cases of unilateral choanal atresia,
      which have presented in adult age group and with complaints not clearly pointing
      to the diagnosis. The role of CT scan in diagnosis and nasal endoscope in the
      treatment has been discussed.

PMID- 23120218
TI  - Impacted knife injury of the orbit, maxilla and oropharynx.
AB  - Injuries in the maxillofacial region with knife in situ are not common. We report
      a rare case with knife impacted in the orbit, maxilla and soft palate. Removal
      was possible only by surgical intervention. Despite the deep penetration, the
      knife had not injured major structures and hence there was no untoward
      complication in the outcome.

PMID- 23120219
TI  - Ectopic multinodular Goitre-An unusual case.
AB  - Ectopic thyroid tissue is usually found in the midline along the path of descent
      of the thyroid gland, such as in the tongue, larynx, trachea, oesophagus, etc.
      Initially, laterally placed thyroid tissues were found to contain malignant
      tissue and hence the term lateral aberrant thyroid tumours. Some attributed these
      to metastatic deposits of primary thyroid carcinoma while others felt that these
      were primary tumours of aberrant thyroid tissue. In later years, benign ectopic
      thyroid tissues were described in the lateral neck. It was felt that ectopic
      thyroid tissues are derived from thyroid cell rests that have failed to fuse with
      the main thyroid tissue during development. They are subjected to the same
      goitrogenic stimulation as the normally placed thyroid tissue. Our case supports
      the view that not all laterally placed thyroid tissues are malignant and also
      presents an unusual subplatysmal location of ectopic thyroid tissue.

PMID- 23120220
TI  - A rare case of Rosai-Dorfman disease of the paranasal sinuses.
AB  - An unusual case of a 6-year-old male child presenting with a history of bilateral
      nasal obstruction of 3 years duration is reported. Endoscopic surgery was
      performed and the specimen sent for histopathological examination. The report
      revealed the surprise diagnosis of Rosai-Dorfman disease. This case of isolated
      extranodal involvement (paranasal sinuses) by this disease is presented and the
      literature available reviewed.

PMID- 23120221
TI  - Naso-oropharyngeal rhinosporidiosis: Endoscopic removal.
AB  - Rhinosporidiosis is a chronic infestation by the fungus Rhinosporidium seeberi,
      which predominantly affects the mucus membranes of the nose and nasopharynx. We
      report a case of rhinosporidiosis with presentation as an oropharyngeal mass and
      a discusion about its endoscopic removal.

PMID- 23120222
TI  - Ameloblastoma mandible: Repair by iliac crest graft following hemimandibulectomy.

PMID- 23120224
TI  - From the editorial Chairman's Desk...

PMID- 23120223
TI  - Micro ear surgery-Its purpose and procedure for tubo tympanic pathology.
AB  - Hearing is one of the special senses god has bestowed upon human beings. One can
      really appreciate the value of hearing only when one ceases to hear.
      Unfortunately, in our country the hearing impaired individuals are ridiculed,
      where as the visually impaired are sympathized upon. Our country being a
      developing nation with poor socio-economic status and low environmental
      surroundings, chronic diseases of the ear account for nearly 5% of the
      population. One will not be surprised if the statistics reveal five crores
      chronic ear patients in our country. If this ailment is not corrected, the
      hardship faced by the patients will be tremendous. Hence, the purpose of ear
      surgery is to restore normal anatomical and physiological status of the ear, so
      that the patient leads a comfortable lifestyle. ENT surgeons by performing
      corrective surgery for chronic suppurative otitis media (CSOM) can change the
      lifestyles of their patients profoundly. The medical line of management will only
      lessen the severity of symptoms. With the present modern gadgets coupled with
      skill acquired by otologist. I will exhort every patient with CSOM to undergo
      corrective ear surgery as to ensure a healthy and normal life.

PMID- 23120225
TI  - Hearty greetings from Hyderabad.

PMID- 23120226
TI  - Preauricular sinus: Operating microscope improves outcome.
AB  - A retrospective review of preauricular sinuses operated in Sundaram Medical
      Foundation, a 140-bedded tertiary care hospital during the period 1995 to 2000 is
      presented. Patients were operated six to eight weeks after control of infection.
      Magnification with an operating microscope was always used. A team of ENT and
      Plastic surgeons was involved in all the cases. Involvement of a Plastic and
      Reconstructive surgeon permitted primary closure after surgery without any
      drains, individualised incisions in every patient, and early discharge from
      hospital. A follow up of all operated patients for a period of 18 months revealed
      good results without any recurrence.

PMID- 23120227
TI  - Endonasal carbon-dioxide laser assisted dacryocystorhinostomy verses external
      dacryocystorhinostomy.
AB  - This is a prospective, non-randomized study to evaluate and compare the results,
      morbidity and surgical time for endonasal carbon-dioxide laser assisted
      dacryocystorhinostomy and external dacryocystorhinostomy. 70 consecutive patients
      of chronic dacryocystitis with nasolacrimal duct obstruction were selected for
      the study. 36 patients under went endonasal CO2 laser assisted
      dacryocystorhinostomy and 34 had external dacryocystorhinostomy. Selection of the
      type of operation was left to the patient's choice. All the patients had
      preoperative counseling and both the procedures were explained in detail with
      their advantages and disadvantages. Patients not willing for the external
      incision were selected for endonasal laser assisted dacryocystorhinostomy and
      others were operated via external approach. Silicone tubes were put in all the
      patients for three months after surgery. The final follow up was 12 months after
      the removal of silicone tubes. The patency of the lacrimal passage was confirmed
      by irrigation, and patients were questioned about their symptoms.The success
      rates, 12 months after removal of silicone tubes were 100% in endonasal CO2 laser
      assisted dacryocystorhinostomy and 88.24% in external dacryocystorhinostomy. The
      surgical time of endonasal laser assisted dacryocystorhinostomy was 38 minutes as
      compared to 62 in external dacryocystorhinostomy. Complication rate in both
      groups was almost equal.Thus, we came to the conclusion that Endonasal CO2 laser
      assisted dacryocystorhinostomy is a better surgical option to external
      dacryocystorhinostomy in cases of chronic dacryocystitis with nasolacrimal duct
      obstruction, with shorter surgical time.

PMID- 23120228
TI  - Prevalence of head and neck cancers in the north east-An institutional study.
AB  - In India, head and neck cancers (HNCA) account for 30-40% cancers at all sites.
      In North-eastern India, where this study was conducted, tobacco related oral
      cancer is very common which may be due to widespread habit of chewing tobacco.
      The lack of any study in this regard and alarmingly high prevalence of cancers of
      head and neck in this part of India has prompted us to take up this study. A
      retrospective study on prevalence of cancer in various head and neck regions like
      oropharynx, oral cavity, pharynx, larynx, oesophagus and nasal cavity was
      conducted in Department of Otolaryngology, Silchar Medical College and Hospital
      from 1993 to 2004.The prevalence is found to be significantly high at 54.48%,
      affecting males more than females in the age group of 40-69 years. HNCA of
      oropharynx and oral cavity constituted a major burden of total body cancer.This
      study hopes to quantify and analyze the spectrum of HNCA and should help as a
      starting point for a much needed population based study in this region. A
      comprehensive effort is needed to identify the cause of such high prevalence,
      generate awareness and treatment options suited to meet this challenge.

PMID- 23120229
TI  - Puberphonia: A novel approach to treatment.
AB  - Puberphonia affects the adolescent males. Authors have used a novel approach by
      using a Macintosh laryngoscope for stretching of vocal cords, which gives
      immediate and permanent relief. This procedure, which was incidentally found to
      be useful, while doing a laryngoscopic examination of a puberphonic patient, was
      effective and superior to any method used in the past 26 cases treated during
      1991 to 2005 had been followed with the excellent results.

PMID- 23120230
TI  - Endoscopic self-expandable metal stenting for advanced carcinoma oesophagus: A
      better palliative prospective.
AB  - Endoscopic placement of metal stent is an established palliative method for
      advanced inoperable cases of carcinoma oesophagus. Although various types of
      prosthesis are available, but the recent development of self-expandable metal
      stents has gained popularity because of less procedure related complications. We
      present the technique and result of ultraflex self-expandable metal stenting,
      which was placed by us in a small series of six patients successfully.

PMID- 23120231
TI  - Surgical anatomy of tympano-mastoid segment of facial nerve.
AB  - OBJECTIVE: Facial nerve is known to have a considerable variations more so in the
      temporal bone. An otologist with inadequate familiarity with facial nerve usually
      have a tendency to do incomplete surgery in chronic suppurative otitis media. The
      present study was conducted to explore the microanatomy of tympanic and mastoid
      segments of facial nerve. SETTING: Temporal bone lab. MATERIALS AND METHODS: This
      study was conducted at PGIMS Rohtak in 25 wet temporal bones which were dissected
      under the microscope. Various parameters studied included the length of tympanic
      and mastoid segments of facial nerve, various anomalies, depth from the cortex
      and relation to various important structures. RESULTS: The mean length of
      tympanic segment was 11.1 mm+/-0.88 and mastoid segment was 15.4 mm+/-2.4. The
      angle at second genu was 95-125 degrees  and the facial canal was dehiscent in
      12% cases. CONCLUSIONS: The tympanomastoid segment of facial nerve has variations
      in length and in its relation with various middle ear structures. Further the
      nerve, in Indians is also at variance as compared to Japanese and Americans
      probably because of different racial configuration of the skull.

PMID- 23120232
TI  - Supravital staining: It's role in detecting early malignancies.
AB  - The efficacy of supravital staining in the detection of malignancies in oro and
      oropharyngeal lesions and its role in the detection of malignant changes in
      premalignant lesions were studied. This prospective study comprises 90 cases of
      clinically suspicious lesions and it was done over a period of 3 years. Most of
      the patients had multiple risk factors for the development of malignancy. All
      underwent staining with a modified solution of 1% toluidine blue (TB). In our
      study the overall sensitivity was 97.29% and the specificity was 62.5%.

PMID- 23120233
TI  - Clinical study of otological manifestations in cases of cleft palate.
AB  - Cleft palate (with or without cleft lip) occurs in about 1: 750-1: 2000 births in
      different societies in the world. Cleft palate individuals have a greater
      incidence of hearing loss than the general population. The primary cause of the
      ear problem in cleft patients is eustachian tube dysfunction. The cause for which
      is abnormal insertion of levator veli palatini and tensor veli palatini muscles
      into the posterior margin of the hard palate and the palatal aponeurosis and
      associated muscular hypoplasia.

PMID- 23120234
TI  - Experiences of day care surgery in otolaryngology.
AB  - Day care surgery in otolaryngology is gradually gaining popularity all around the
      world and the scope of day care surgery has improved significantly in recent
      years.380 patients underwent ear, nose and throat surgery during the period Sep
      2002-Aug2004. All the cases were done under local anaesthesia. Strict criteria
      were adopted for admission and discharge of the patients.Most of the patients
      (90.6%) who underwent ENT day care surgery did not experience unusual
      peroperative or postoperative discomfort. There was no case requiring
      postoperative admission to a hospital. There was a high degree of patient
      preference and satisfaction to day care surgery.Following proper guide lines for
      day care surgery and strict admission and discharge criteria has gone a long way
      in making day care surgery a success. It can be concluded that high medical
      standards can be achieved with low expenditure with this form of management.

PMID- 23120235
TI  - A study on the clinical profile and management of inverted Papilloma.
AB  - Inverted Papilloma is a unique neoplasm characterized by its tendency to destroy
      bone, tendency to recur after incomplete removal and association with malignancy.
      The uncertainty of its clinical features and projected behaviour has resulted in
      an ill-defined approach to its management. This is a prospective study of 30
      patients of Inverted Papilloma admitted at Regional Institute of Medical
      Sciences, Imphal between August 2001 to July 2003. In this study, meticulous
      attention is given to the clinical presentation and management in a series of 30
      patients with inverted papilloma. A majority of patients were between 50-70 years
      (40%) with a mean age of 52.3 years. M: F Ratio=3.3:1. Commonest presenting
      symptoms were unilateral nasal obstruction (93.3%), nasal discharge (40%) and
      epistaxis (36.6%). 90% of the patients had signs of involvement of the nasal
      cavity with one or more sinuses and 46% showed bony erosion on C.T. Scan studies.
      Surgery was the treatment of choice in 90% of the cases.

PMID- 23120236
TI  - Effects of irradiation on nasal mucociliary clearance in head and neck cancer
      patients.
AB  - A prospective longitudinal study was conducted on fifty patients of
      histopathologically confirmed head and neck cancer with the main aim to assess
      the nasal mucociliary clearance, pre-and post-irradiation; and to compare the
      findings with the healthy non-irradiated age and sex-matched controls. All the
      patients underwent saccharin particle test for nasal mucociliary clearance before
      commencement of radiation therapy and again within 6 months of completion of
      radiation therapy. The difference between the saccharin perception times of nasal
      mucosa in the healthy non-irradiated controls and the pre-irradiated head and
      neck cancer patients were statistically inssignificant (P>0.05). But, the
      difference between the saccharin perception times of nasal mucosa in the pre-and
      post-irradiated head and neck cancer patients was found to be statistically
      significant (P=0). It is concluded that even indirect irradiation of nasal mucosa
      in head and neck cancer patients significantly affect its ciliary activity.
      Significance of total radiation dosage along with chemotherapy in some cases was
      also studied.

PMID- 23120237
TI  - Reconstruction of nasal defects our three years experience.
AB  - This paper recount our experience with reconstructing various nasal defects in 44
      patients operated in our institute over last 3 years by using various flaps This
      is a prospective study Our hospital prefabricated scalping flap are the flaps of
      choice. Free radial artery forearm flaps are also useful in large defects
      reconstruction.

PMID- 23120238
TI  - Comparison of sequential chemoradiation with radiation alone in the treatment of
      advanced head and neck cancers.
AB  - OBJECTIVES: To compare locoregional control with alternating chemo radiation and
      radiation alone in patients with locally advanced head and neck carcinoma. STUDY
      DESIGN: A prospective randomized study. SETTING: Tertiary academic referral
      center. PATIENTS: 50 patients of biopsy proven locally-advanced carcinoma of head
      and neck. INTERVENTION: 25 patients were kept in Group I or study group (i.e.
      alternating chemo-radiation) and 25 patients in Group II or control group (i.e.
      radiation alone). In the study group, patients were given 3 cycles of
      chemotherapy (Cisplatin 20 mg/m([2]) and Inj. 5-FU 200mg/m([2]) from day 1-5 of
      each week) during weeks 1,5 and 9 alternated with radiation dose of 10Gy/week was
      given during weeks 2,3,4 and 6,7,8. In the control group, patients were given a
      total dose of 60Gy in 6 weeks. OUTCOME MEASURES: The response rate at the primary
      site and nodal site was better in study group as compared to control group.
      RESULTS: On comparing the response at the primary and nodal site together, 72%
      (18/25) patients of group I and 44% (11/25) patients of group II showed CR. PR
      was seen in 28% (7/25) and 36% (9/25) patients in group I and II respectively. No
      response was seen in 5/25 (20%) of patients in Group II. CONCLUSION: Our study
      has revealed that alternating/ sequential chemoradiation is a promising and
      feasible approach for patients in advanced head and neck cancer.

PMID- 23120239
TI  - Ear abuse in school children.
AB  - Ear abuse in school children is common in low socio-economic strata and is often
      associated a long-term morbidity in our country. This paper presents a study of
      250 such children with discussion. Incidence of ear abuse with long term learning
      deficit was found to be 18.4%.

PMID- 23120240
TI  - Foreign bodies in upper digestive tract.
AB  - Foreign body ingestion is a common problem frequently encountered in both
      children and adults. A total number of 152 patients (104 children and 48 adults)
      with ingested foreign body admitted in our hospital are reviewed. Location of
      foreign body was made out by radiological examination. History of having
      swallowed foreign body was the most common symptom in both blunt and sharp
      foreign bodies. Endoscopic removal of foreign body was done under general
      anaesthesia for all cases, except one in which foreign body was removed by open
      surgical method. Blunt, foreign bodies were common among children, where as meat
      with bone was common in adults (19/48). Most of blunt foreign bodies in children
      (83.5%) were impacted in post cricoid region. Where as in adutls, the foreign
      bodies (37.5%) were seen in upper oesophagus. Retropharyngeal abscess was seen in
      2 cases, which was associated with sharp foreign bodies. In all but one,
      endoscopic removal was successful. In one case denture impacted in post cricoid
      region was removed by open surgical method. There was no mortality in our series.

PMID- 23120241
TI  - Clinical audit of outcomes in Cochlear Implantation an Indian experience.
AB  - This retrospective study is based on the assessment of outcomes of Cochlear
      Implantation taking into account various scoring systems like Category of
      Auditory Performance (CAP) and Speech Intelligibility Rating (SIR). 100
      candidates who were implanted between June 1997-June 2005 at Madras ENT Research
      Foundation (MERF), a tertiary referral center for cochlear implantation were
      included in the study. The results were analyzed using the above scoring systems
      to assess the performance levels of each implantee and to arrive at a cumulative
      result on the outcome of the implantation. Practical issues of concern to
      Cochlear Implantation in the Indian subcontinent were also analyzed.

PMID- 23120242
TI  - Retained, incarcerated oropharyngeal foreign bodies.
AB  - Foreign body ingestion is a well documented entity. Incarcerated oropharyngel
      foreign bodies are fre quently observed. Care should be taken for the symptoms
      like dysphagia and odynophagia, even if no positive history for foreign body
      ingestion is present. Two cases of incarcerated oropharyngeal foreign bodies are
      presented here who did not report with history of foreign body ingestion.

PMID- 23120243
TI  - Malignancy larynx presenting solely as pharyngo-cutaneous fistula.
AB  - Malignancy larynx usually presents early, the common symptoms being hoarseness,
      pain thorat, cough and irritation of throat. An advanced malignancy is likely to
      be complicated by a pharyngo-cutaneous fistula. However it is an occurrence
      towards the end stage of the disease. Here we present a case of malignancy larynx
      primarily presenting as pharyngo-cutaneous fistula without any other symptoms.

PMID- 23120244
TI  - Cavernous haemangioma of the parapharyngeal space.
AB  - Parapharyngeal space swellings due to various pathological processes have been
      reported in the literature. We report a case of cavernous haemangioma of the
      parapharyngeal space in an adult female patient. To the best of our knowledge
      this is the first such case reported in the English literature.

PMID- 23120245
TI  - Removal of foreign body from the trachea: An unusual method.
AB  - Tracheobronchial foreign bodies can be sometimes very difficult to remove. This
      may be related to the location and type of foreign body, experience of the
      bronchoscopist and the availability of appropriate instruments.([1]) We report a
      case of an uncommon foreign body (artificial denture) in the trachea in an adult
      female following extubation after Lower Segment Caesarian Section (LSCS) in whom
      conventional methods to remove it failed. The foreign body was eventually removed
      via tracheostome using rigid bronchoscope and forceps.

PMID- 23120246
TI  - Actinomycosis of faucial tonsil masquerading as oropharyngeal malignancy.
AB  - Actinomycosis is a rare inflammatory disease caused by anaerobic gram negative
      bacterium of actinomyces species. Lesions in the head and neck are characterized
      by their varied presentation and their propensity to mimic other diseases.([1])
      Here we present a rare case report of actinomycosis of tonsil in an elderly man
      masquerading as tumour of oropharynx.

PMID- 23120247
TI  - Orbital Apex Syndrome due to mucormycosis caused by Rhizopus microsporum.
AB  - The incidence of fungal rhino sinusitis has increased in recent years in a
      tropical country like India. A case of Orbital Apex Syndrome due to mucormycosis
      caused by Rhizopus microsporum fungus is reported in a 65 year old male diabetic
      patient. The disease though invasive with early diagnosis and treatment, has a
      good prognosis with a favorable outcome.

PMID- 23120248
TI  - Primary lingual tuberculosis presenting as cold -Abscess tongue: A case report.
AB  - Oral manifestation of tuberculosis is uncommon Tongue is the most common oral
      site of involvement, where the presentations are varied. Here we report a case of
      primary lingual tuberculosis with an unusual presentation as a cold abscess.

PMID- 23120249
TI  - Neglected foreign body in oesophagus with an unusual presentation: A case report.
AB  - Foreign body in oesophagus is not an unusual finding, we report here a case of
      neglected foreign body in oesophagus with an unusual presentation which remained
      almost asymptomatic for three years before removal.

PMID- 23120250
TI  - An unusual aetiology of unilateral vagal palsy: A case report.
AB  - Vagal palsy is often a diagnostic challenge because the nerve can be affected
      anywhere along its course, from the point of exit from cranial vault through the
      jugular foramen upto its destination. This is a case report of a 78 year old lady
      who presented to our department with clinical features suggestive of unilateral
      vagal palsy and whose diagnostic evaluation revealed a Lateral Mass Fracture of
      Atlas vertebra with displacement of the fragment.

PMID- 23120251
TI  - Differentiated thyroid cancer invading the hypopharynx: A case report.
AB  - Most thyroid cancers (90-95%) are well differentiated. Well differentiated
      cancers of the thyroid are usually confined to the thyroid capsule, making them
      amenable to isolated thyroid resection. Invasion of the upper aerodigestive tract
      by these cancers is infrequent and hypopharyngeal invasion is still rare. We
      report a 51 year old man with thyroid cancer invading the hypopharynx, who was
      successfully managed with complete resection along with a partial pharyngectomy.
      He is asymptomatic and disease free eighteen months after surgery. We advocate
      aggressive surgical extirpation of thyroid carcinoma invading the upper
      aerodigestive tract.

PMID- 23120252
TI  - Carotid space infection: A case report.
AB  - A case of isolated carotid space abscess is reported here for its rarity. No
      identifiable cause was detected in this case. Management involved incision and
      drainage of the abscess, close monitoring for the signs of complications and 8
      weeks long antibiotic coverage. The only stigma of the abscess six months after
      presentation is a unilateral vocal cord palsy. A brief review of relate
      literature is also included.

PMID- 23120253
TI  - Goldenhar-Gorlin's syndrome: A case report.
AB  - Goldenhar syndrome, a term synonymously used with "oculo-auriculo-vertebral" [1]
      spectrum is a rare disorder that is apparent at birth. Described as early as
      1950's it was initially comprised of malformation of ears and ocular
      abnormalities it was only in 1963 that vertebral abnormalities were included as
      signs of this syndrome. This work reports a case 12 year old male who presented
      in department of GMC with dysmorphic ears and on evaluation was found to have the
      classical signs of this syndrome. This case did not have the classical ocular
      findings. Also included is the current protocol for treatment of this syndrome.

PMID- 23120254
TI  - A rare case of primary nasoethmoidal meningioma.
AB  - Meningiomas of sinonasal tract is a rare entity especially in children. Primary
      sinonasal meningiomas often pose difficulty in diagnosis because of their
      infrequent occurrence and clinically they appear to be nasal polyp. The final
      diagnosis rests on the histological examination. Extra cranial meningiomas are
      rare in children and tend to be more aggressive. Here a case of primary ethmoid
      sinus meningoma with extension into the nasal cavity is presented and despite of
      its aggressive behavior it was benign. The importance of complete surgical
      extirpapion is undoubted and results in a good survival rate. Histological
      grading of the tumour is not crucial in predicting the rate of recurrence. The
      paucity of reported cases is the evidence for its rarity.

PMID- 23120255
TI  - Fibrosarcoma of the maxillary sinus.
AB  - Fibrosarcoma arising in the sinonasal cavities are very rare. By the time of
      clinical diagnosis, they are usually advanced. Lack of adequate surgical margins
      predisposes these patients to tumor recurrences. Most common sites are the
      extremities, with only one percent of fibrosarcoma arising in the head and neck
      area. The imaging features of these tumors reflect their aggressive behavior. We
      report the case of a maxillary sinus fibrosarcoma in a 16 year-old male patient.
      Neoadjuvant chemotherapy, medial maxillectomy, adjuvant chemotherapy and
      subsequent external irradiation was perfomed.

PMID- 23120256
TI  - An amazing case of working wrist watch in the esophagus.
AB  - Foreign bodies in the esophagus are commonly seen in otolaryngologic practice. We
      report the successful removal of a working wrist watch dial lodged for one month
      in the esophagus of an adult schizophrenic patient, which is a rare incident.

PMID- 23120257
TI  - How a bronchoscopy avoided a pediatric pneumonectomy!
AB  - Primary Lung pathology without any intraluminal lesion needs extensive lung
      resections but It is always necessary to rule out any intraluminal pathology
      before submitting the patient to a Pneumonectomy. The case described illustrates
      how a last minute, on the table Exploratory Bronchoscopy revealed a Broncholith
      which avoided an extensive surgery thus reducing the morbidity.

PMID- 23120258
TI  - Silent mastoiditis-tuberculous aetiology presenting as facial nerve palsy.
AB  - We report an unusual case of sudden onset lower motor neuron facial palsy in a 30
      year-old male. It was subsequently diagnosed to be caused by silent mastoiditis
      of tuberculous aetiology. The diagnosis was based on the histology of
      granulations found during facial nerve decompression. The facial palsy resolved
      after initiating anti-tubercular therapy and surgical decompression. Our case is
      an uncommon case of acute onset infranuclear facial palsy due to tuberculosis, in
      the absence of any ear findings, resembling Bell's palsy.

PMID- 23120260
TI  - Editorial.

PMID- 23120259
TI  - Multiple myeloma presenting as stridor: A case report.
AB  - Extrame dullary plasmacytoma of larynx is extremely rare. We report a case of
      multiple myeloma which presented as extrame dullary manifestation in larynx. The
      rarity of incidence and difficulty in diagnosis of the disease is discussed.

PMID- 23120261
TI  - Laryngopharyngeal reconstruction.
AB  - There is a high incidence of hypopharyngeal cancer is our country due to the
      habits of tobacco and alcohol. Moreover these cases are often detected in the
      late stages thereby making the issue of reconstruction very tedious and
      unpredictable. There are a number of options for laryngopharyngeal reconstruction
      available now including the use of microvascular flaps depending upon the
      patient's fitness, motivation, technical expertise, size and extent of the
      defect. This article reviews the different methods of laryngopharyngeal repair as
      regards their success rate, radiation tolerance, morbidity & mortality.

PMID- 23120262
TI  - Parapharyngeal space tumours a radiological and surgical correlation.
AB  - The parapharyngeal space is a deeply situated space on either side of head.
      Clinical assessment of lesions in this space in very difficult. 28 patients with
      parapharyngeal space masses diagnosed and managed in the department of
      Otorhinolaryngology and Head & Neck Surgery of Postgraduate Institute of Medical
      Education and Research. Chandigarh were studied. 8 patients were excluded as the
      tumour could not be removed en-bloc in these. 20 were analysed further.

PMID- 23120263
TI  - Tympanosclerosis revisited.
AB  - Tympanosclerosis is a common clinico-pathological entity encountered by the
      otosurgeon. Its pathogenesis and optimum management have eluded the otologists
      since time immemorial. The present study was undertaken to study the incidence of
      tympanosclerosis amongst patients with chronic suppurative otitis media and to
      study the correlation between the degree of hearing loss and the site of
      tympanosclerosis. Audiometric and operative findings of 200 patients of chronic
      suppurative otitis media were analysed. The incidence of tympanosclerosis was
      found to be 19% (3d cases out of 200 patients). Most cases of tympanosclerosis
      had a dry ear on presentation (78.9%). When tympanosclerosis was confined only to
      the tympanic membrane. 83.3% of the cases had an air-bone-gap less than 40 dB. On
      the other hand, when tympanosclerosis affected both the tympanic membrane and the
      middle ear. 75% of the cases had an air-bone-gap more than 40 dB. The hearing
      loss associated with tympanosclerosis was of the conductive type in the majority
      of cases. Ossicular mobility was found to be normal in 71.1% of the cases.

PMID- 23120264
TI  - Middle ear microsurgery in india: a retrospective audit study.
AB  - Around 2000 ENT Surgeons perform about 120000 middle ear microsurgery operations
      annually in India while the burden of otitis media is 50 million cases. A
      comprehensive questionnaire consisting of personal details of surgeons, his
      infrastructure, results, and complications was sent to 2000 ENT Surgeons from the
      latest AOI Directory. 400 Surgeons responded back from all over the country and
      the data collected was fed into a computer program and was analysed. Most of the
      responses were from western and southern parts of India. Almost all those who
      responded were performing myringoplasty while only 47 percent performed
      ossiculoplasty and 40 percent stapes surgery. Senior surgeons (more than 5 years
      after post graduation) had better infrastructure and better results as compared
      to junior surgeons, (less than 5 years). About 60 percent surgeons had Indian
      operating microscopes (commonest 80 percent being BEL) while 40 percent could
      afford foreign made microscopes (90 percent being Karl Zeiss). The procedure of
      myringoplasty is almost standardized while there is need to popularize
      ossiculoplasty and stupes surgery. Need was felt for technology transfer
      programmes from Southern and Western parts of India to Northern and Eastern parts
      of India.

PMID- 23120265
TI  - Role of F.E.S.S. in chronic sinusitis.
AB  - Functional endoscopic sinus surgery (FESS) is a new and exciting treatment for
      chronic sinus disease. A prospective study of 50 patients undergoing FESS was
      undertaken at the department of Otolaryngology, Dayanand Medical College &
      Hospital, Ludhiana. Parameters studied included patient symptoms, medical
      history, medical therapy, radiologic findings, complications and postoperative
      symptoms. 62% of our patients had sinonasal polypi (ethmoidal polypi 56%,
      antrochoanal polypi 6%) while 38% had chronic sinusitis. Osteomeatal complex
      involvement (88%) was the most common preoperative CT scan findings. All the
      cases were subsequently suhjected to functional endoscopic sinus surgery, studied
      for post-operative complications and 82% of the patients achieved improvement in
      preoperative symptoms. It was concluded that FESS is a highly successful
      treatment for chronic sinus disease.

PMID- 23120266
TI  - Post-tonsilelectomy morbidity - do steroids help.
AB  - A prospective randomized controlled study was conducted in 50 patients evaluating
      the effect of single intra - operative intravenous dose of dexamethasone on post 
      operative morbidity. Dexamethasone was found to significantly reduce the
      incidence of vomiting in 1(st) 24 hrs, trismus. pain, time for 1(st) solid
      intake, need to administer rescue analgesic and fever. Besides the number of
      school days lost in study group were less compared to control due to earlier
      feeling of well being.

PMID- 23120267
TI  - Rhinoplasty - our experience.
AB  - The increasing awareness of rhinoplasty as a cosmetic surgery and the increasing
      number of patients seeking rhinoplastic surgery motivated us to do this study. 30
      cases in whom rhinoplasty was done were monitored with regard to the various
      deformities present, the different aurgical steps undertaken for their
      correction, the complications encountered and the results achieved. Though the
      basic surgical steps remain more or less same, modifications according to
      individual need and surgical acumen, a proper preoperative counselling and a
      realistic level of expectation in both the surgeon and the patient can give a
      satisfactory result in a great majority of cases.

PMID- 23120268
TI  - Comrarative study of infiltration and surface application of bupivacaine in post
      tonsillectomy pain.
AB  - The concept of preamptive analgesia using bupivacaine to minimize post operative
      pain is a well established fact in surgery today. But the role ol bupivacaine to
      control post operative pain in tonsillectomy is still viewed with some degree of
      suspicion. The review of medical literature gives us conflicting views regarding
      its use. We present a randomised double blind study of 80 cases in which
      bupivacaine was used in the form of infilteration (preoperatively and packs
      (postoperatively) to minimize post tonsillectomy pain. The results were
      statistically analysed using 't' test and bupivacaine was found to be highly
      effective in minimizing post operative tonsillectomy pain. But the superiority of
      one method of application over the other could not be established.

PMID- 23120269
TI  - Chronic suppurative otitis media in school going children.
AB  - The morbidity and mortality associated with otitis media is really a challenge
      for the health care systems. This study is a small attempt to look into the
      magnitude of this problem in the society, where in school going children in
      Yavatmal city were studied. A total of 4104 students were studied. It was found
      that the overall prevalence of chronic suppurative otitis media in Yavatmal city
      is 3%. The incidence of acute otitis media was found to be 1.3% Chronic
      suppurative otitis media was commoner in students belonging to low socioeconomic
      strata and its association with adenoid hypertrophy was statistically
      significant. The authors recommend that a few more such studies should be carried
      out in different parts of the country to collect vital data for the health care
      system managers. Suppurative otitis media, school children, Yavatmal city.

PMID- 23120270
TI  - Pseudocyst of auricle - etiopathogenesis, treatement update and literature
      review.
AB  - Pseudocyst of the pinna, a benign idiopathic cystic swelling is an uncommon
      condition. In the medline search there are over 113 cases reported in literature.
      Engel in 1966 reported the incidence in Chinese community. In this review article
      we describe the etiopathogenesis, demographic statistics and treatment
      modalities.This is a retrospective study of six cases treated by the senior
      author in the dept of Otorhinolaryngology, Head & Neck Surgery, Apollo Hospital
      Chennai, South India between 1993 through 2003. There is preponderance of
      incidence in adult male (5 cases) and a single case in a female. The author
      highlights the modalities of treatment and opines that the surgical technique
      described by Lim et al, with little modification is the gold standard, which
      retains the architecture of the pinna. Conservative methods adopted by others
      have failed.

PMID- 23120271
TI  - Role of routine coagulation studies in idiopathic epistaxis.
AB  - Epistaxis, being the commonest ENT emergency requiring hospital admission, is
      clearly an important condition - not only to the specialist but also to any
      general practitioner. The role of routine coagulation studies in the management
      of patients suffering from epistaxis is unclear. In an attempt to address this
      issue, the prospective case study was carried out in the department of ENT in
      Government medical college and hospital Nagpur over span of 2 years from October
      2001 to November 2003 in which 100 cases were studied. Coagulation studies were
      carried out in 100 patients but only 7 patients had abnormal coagulation profile.
      No other coagulation abnormalities were identified. This study supports the view
      that there does not appear to br role for routine coagulation studies in patients
      of epistaxis. The investigation for potential haemostatic disorder should be
      performed when clinically indicated and if necessary, in consultation with the
      hematology service.

PMID- 23120272
TI  - Endoscopic hypophysectomy.
AB  - The minimally invasive endoscopic pituitary surgery is performed through the
      natural nasal pathway without any incisions unlike the conventional microscopic
      surgery performed via Trans-nasal Trans-sphenoidal upproach. We have tried to
      compare the clinical implications of these two approaches. In our study,
      conducted from 1995 to 2004, we started operating pituitary adenomas with
      conventional Trans nasal Trans-sphenoidal microscopic approach and later used the
      endoscopic assisted approach and then endoscopic. Close and long period of follow
      up was maintained. In our experience of 9 years, adopting the endoscope not only
      eliminates the need for nasal packing, but also heightens the surgeons'
      visualization of pituitary tumors, thus no external incision, no nasal packing
      and overnight stay with no complications.

PMID- 23120273
TI  - Comparative study of tympanoplasty in wet perforation v/s totally dry perforation
      in tubotympanic disease.
AB  - In our initial experience the failure rate in totally dry ear Tympanoplasty were
      more as compared to wet Tympanoplasty. Hence we suspected the avascularity of
      totally dry tympanic membrane is the cause for such failures. So we did
      histopathological study of both types of remnant tympanic membrane & compared the
      finding. According to the results we infer that graft take up rate is better in
      wet central perforation than totally dry perforation following tympanoplasty, so
      is the success rate. This also correlates with our clinical experience. We have
      further seen that such types of failures can he prevented, if(i) the central
      perforation is converted to subtotal perforation by removing the necrotic portion
      of the TM, (ii) stabilization of the underlay graft by antero-superior anchoring
      myringoplasty in which a window in the anterior canal skin is made at about 3
      O'clock position in right ear & 9 O'clock position in left ear and the graft is
      tucked under it.

PMID- 23120274
TI  - Cochlear implantation in multi-handicapped patients: the merf experience.
AB  - Hearing loss is the most common form of sensory impairment in humans. When
      hearing impairment is present from birth or is acquired in early childhood, it
      can be devastating for normal development. Early childhood deafness also has
      implications for cognitive, emotional and social development. In the majority of
      cases of early childhood hearing impairment, deafness is an isolated disorder.
      However, in a substantial number of cases, early childhood hearing impairment is
      not isolated, but forms part of a genetic syndrome with associated handicaps, or
      is acquired through pre-, perior postnatal causes, possibly with associated
      deficits. This means that more demands are made on the child's family, the
      teachers and medical professionals to help these children cope with their
      rehabilitation, needs and demands. The presence of an additional handicap can
      pose special problems with regard to surgery, anesthesia or rehabilitation.
      Cochlear implantation is effective and aids in the effective rehabilitation of
      other additional handicaps. However, careful patient selection is required and
      thorough parental counseling regarding expectations must be given. In our
      Cochlear Implant Clinic a large proportion of implantees are in the paediatric
      age group. Of these, a few have had multiple disabilities in addition to their
      deafness. This paper attempts to share our experience in this extremely
      challenging and specialized field.

PMID- 23120275
TI  - Reduction of Adam's apple for appearance.

PMID- 23120276
TI  - Hemangiopericytoma like tumor - a diagnostic challenge.
AB  - Haemangjopericytoma is a vascular tumour rarely seen in common practice,
      especially in head & neck. Hemangjopericytoma - like tumor is an even more rare
      entity and only 70 cases have been described arising from the nose & paranasal
      sinuses. The aim of this paper is to review the literature and highlight the
      ability of the tumor to masquerade as a less ominous, more commonly occurring
      benign growth of the region thereby making the diagnosis even more elusive.

PMID- 23120277
TI  - Cochlear sequestrum - An uncommon complication of a common disease.
AB  - Sequestration of the inner ear is an unusual complication of chronic suppurative
      otitis media. More so when not associated with a cholesteatoma. We report a rare
      case of tubotympanic disease producing multiple complications including a
      cochlear sequestrum.

PMID- 23120278
TI  - Acute epiglottitis: A review of 50 patients.
AB  - We reviewed 50 patients admitted to the department of Otorhinolaryngology and
      Head & Neck Surgery of Govt Medical College Srinagar from September 19% to
      September 2002 diagnosed with acute epiglottitis. Male were more commonly
      involved than females in the ratio of 2.8:1 with only 6 cases younger than 10
      years of age. The highest incidence was in the month of January (22%). The common
      symptoms of acute epiglottitis were sorethroat(92%) and odynophagia(88%). Any
      patient with sudden onset of these symptoms should be suspected of having acute
      epiglottitis and should have an indirect laryngoscopy. Blood culture was obtained
      in 20 cases Cultures were positive only in 5 cases, out of which 4 were positive
      for Hemophilus influenzae type B. Throat cultures were not obtamed The primary
      treatment of acute epiglottitis is intravenous antibiotics, steriods, and
      humidified air. Treacheostomy was needed only in 4 patients. There were no
      deaths.

PMID- 23120279
TI  - Lupus of the upper respiratory tract.
AB  - Lupus is a form of chronic tuberculous infection which can be differentiated from
      tuberculosis only on clinical grounds. Lupus is very rarefy found in the present
      era. A 10 year mule child was diagnosed as a case of lupus on clinical and
      pathological examination.

PMID- 23120280
TI  - Plexiform neurofibromatosis presenting as dysphagia.
AB  - Plexiform neurofibromatosis is a autosomal dominant disease characterized by
      multiple cafe aulait spots, cutaneous neurofibromatosis, CMS tumours and skeletal
      abnormalities. We report a child with plexiform neurofibromatosis presenting with
      dysphagia, an unsual presentation.

PMID- 23120281
TI  - Cysticercosis of tongue - A case report.
AB  - Tongue is a rare site for cysticercosis cellulosae. Very few cases of solitary
      cysticercosis of tongue have been reported. We are reporting one such case. Also
      a review of reported cases in literature, etoipathogenesis, clinical course and
      management is being described.

PMID- 23120282
TI  - Cervical necrotizing soft tissue infection - A case report.
AB  - A small but nevertheless important part of a surgeons experience comprises
      necrotizing soft tissue infections of the head and neck. These infections are
      characterized by their fulminating, devastating, and rapid-progressing course
      resulting in extensive necrosis of fascia, subcutaneous tissues, skin and muscle.
      Although necrotizing facilities is a more frequently used terminology, the
      authors prefer to use the term necrotizing soft tissue infection to describe this
      potentially fatal condition. A case of cervical necrotizing soft tissue infection
      of dental origin is reported here. The purpose of this report is to heighten
      awareness of necrotizing soft tissue infections in any patient with an infection
      of the neck. The article also outlines an appropriate management strategy for use
      in such patients with emphasis on prompt diagnosis and early radical surgical
      debridement.

PMID- 23120283
TI  - Recurrent thyroid abscess - Is it a fourth branchial archanomaly?
AB  - Branchial fistulae are of congenital origin(6) and consists of skin lined tract
      opening internally at junction of cartilaginous and bony meatus in case of 1(st)
      arch anomaly, tonsillar fossa in case of 2(nd) arch, while 3(rd) and 4(th) arch
      sinuses have internal opening at level of pyriform sinus or below. A complete
      tract of 3(rd) or 4(th) arch fistulae is yet to be described. Fourth arch
      fistulae(1) have a distinct clinical pattern of internal opening at pyriform
      apex, are left sided and associated with suppurative thyroiditis(3), they
      manifest at a younger age and treatment involves excision of tract with
      ipsilateral thyroid lobectomy.

PMID- 23120284
TI  - Button cell in oesophagus: An unusual destructive foreign body a case report.
AB  - A case of button cell lodged in oesophagus is reported. The button cells are
      potentially destructive foreign bodies due to damage caused by leakage of harmful
      chemicals and their capability to generate electric current. The mucosal damage
      starts early and may lead to life threatening complications in long standing
      cases. Removal of these should be accorded highest priority to prevent
      complications.

PMID- 23120285
TI  - Retained foreign body in sino-orbital region.
AB  - It is rare to find foreign bodies in nose and paranasal sinuses. The further
      rarity is to encounter impacted foreign body in this region and route of entry
      being through the orbit. We are here by presenting a case, where a metallic
      foreign body was retained for duration of 4 months in sino - orbital region.

PMID- 23120286
TI  - Haemangioendothelioma of paranasal sinuses with intracranial extension.
AB  - Maxillary sinus is a rare site for the occurrence of haemangioendothelioma. The
      present case is being reported in a 45 year old Hindu Male. The main complaint
      ware bilateral nasal obstruction und a mass protruding from he right nostril
      along with episodes of headache, vomiting and nasal bleeding. The. C.T. scan
      showed evidence of erosion of bony walls of maxillary antrum with intracranial
      extension of the tumor. There was no evidence of regional lymph nodes or distance
      metastasis. Histology of the tissue revealed a highly cellular and vascular tumor
      the diagnosis of haemangioendothelioma of the maxillary sinus retiform variety
      was established.

PMID- 23120287
TI  - Second branchial sinus - A case report.
AB  - Branchial apparatus consists of six pairs of mesodermal arches. Invagination of
      endoderm from inside and ectoderm from outside are known as pharyngeal pouch and
      branchial clefts respectively. Incomplete fusion of these structure lead to
      formation of branchial sinus/ fistula. Anomoly of second arch is commonest and
      manifests as Branchial sinus. We present such a case in a 18 years old boy.

PMID- 23120288
TI  - Hanging drop deformity of the nose.
AB  - A chondroid syringoma causing disfigurement of the nasal tip is reported. It is a
      rare tumour which had to be approched with careful thought for cosmesis.

PMID- 23120289
TI  - Hypohidrotic (Anhidrotic) Ectodermal dysplasia - A rare cause of childhood
      Atrophic Rhinitis".
AB  - Hypohydrotic (Anhidrotic) Ectodermal dysplasia is a rare hereditary
      genodermatosis characterized by a triad of defects including hypohidrosis
      hypotrichosis and anomalous dentition. Mainly ectodermal structures are involved
      such as epidermis and its annexes (hair & nails), although non-ecotodermal tissue
      may also became involved(1). ENT involvement in such cases is a consequence of
      the defect involving the eccrine and sebaceous glands. A case of a 3 years old
      female child suffering from hypohidrotic ectodermal dysplasia with features of
      Atrophic Rhinitis from infancy & early childhood is reported here. Management of
      these patients is mainly supportive and otolaryngologist is a vital component of
      the health care team managing such patients.

PMID- 23120290
TI  - Subcutaneous granuloma of the cheek an unusual case report and review of
      literature.
AB  - With the increase in prevalence of extra pulmonary tuberculosis, it has become
      imperative for clinicians to review their knowledge of unusual presentations of
      mycobacterial infections. Tuberculous involvement of the subcutaneous tissue and
      skeletal muscle is rare. Apart from tuberculous lymphadenitis, diagnosis of
      extrapulmonary tuberculosis may be difficult. We present here a case of
      tuberculous granuloma of the cheek - an unusual presentation in ENT practice.

PMID- 23120291
TI  - Metastatic malignant melanoma from unsuspected primary, diagnosed on cervical
      lymphnode FNAC.
AB  - Cervical lymphnodal metastases from unsuspected primary melanoma is a
      particularly refractory clinical diagnostic situation. Judicious use of FNAC may
      render the correct diagnosis if discriminant criteria are strictly adhered to.
      Two cases with enlarged cervical lymphnodes, diagnosed as metastatic malignant
      melanoma on cytology, are reported.

PMID- 23120292
TI  - Recurrent Bell's palsy in children - Report of two cases.

PMID- 23120293
TI  - Unusual case of coin in larynx (glottic chink) presenting as Dysphagia.
AB  - Foreign body larynx is a rare condition in adults - inhalation of coin and
      impaction of the coin in the glottic chink is more rare finding. But this patient
      presented with difficulty in swallowing and speech, without any respiratory
      trouble - Hence the case is reported.

PMID- 23120294
TI  - Tuberculosis of tonsil.
AB  - A rare case of tuberculosis of tonsil in a 32 year old male patient, who
      presented with an ulcero granulomatus lesion of left tonsil which is tender, bled
      on touch. There was an associated left cervical lymphadenopathy. Routine
      laboratory investigations were with in normal limits. FNAC of cervical lymph node
      and Histopathological examination of tonsillar tissue shows tuberculosis. Chest X
      ray revealed bilateral extensive pulmonary kochs. The patient was put on anli
      tubercular therapy with which the patient responds very well.

PMID- 23120295
TI  - Pneumothorax secondary to foreign body inhalation in an infant.
AB  - An unusual case of pneumothorax secondary to inhalation of a vegetative foreign
      body in a seven month old child is presented here for its rarity. Proper and
      timely intervention could save the child.

PMID- 23120296
TI  - Safe thyroidectomy: Our view point.
AB  - Thyroid surgery by an Head & Neck surgeon can only be "Safe" when there is no
      morbidity. Identification and preservation of Recurrent laryngeal Nerve (RLN) and
      Parathyroids is absolutely necessary to ensure a Safe Thyroidectomy. Thorough
      knowledge of anatomy will guide the surgeon to the important landmarks.

PMID- 23120297
TI  - Facial nerve paralysis: A three year retrospective study.
AB  - Of all the cranial nerves, the facial nerve is the one which is most commonly
      involved in disease. Facial paralysis leaves the patient severely disfigured.
      Timely diagnosis and treatment can lead to considerable recovery. 16 consecutive
      patients of facial paralysis of all age groups and due to different causes
      diagnosed and treated in a tertiary referral hospital have been studied
      retrospectively. The frequency of aetiological factors, the various factors
      governing the management of these cases and their actual outcomes after a minimum
      period of one year are discussed. The causes of facial nerve palsy included
      cholesteatomas, Bell's Palsy, iatrogenic, traumatic, neuroma and others. In
      general, early reporting, diagnosis and surgical intervention wherever indicated
      have resulted in better recovery. Surgical decompression of the facial nerve
      traditionally advocated have been questioned. Rare causes of facial nerve
      paralysis like postoperative BIPP pack allergy and bilateral congenital agenesis
      of facial nerve are also included.

PMID- 23120299
TI  - Surgical management of trismus due to Oral Submucous Fibrosis - Lysis of fibrotic
      bands with the KTP-532 Laser.
AB  - Oral Submucous Fibrosis is an insidious, chronic disease affecting the oral
      cavity, sometimes the pharynx and rarely the tongue. 15 patients with Oral
      Submucous Fibrosis presenting with severe trismus were treated with lysis of the
      fibrotic bands with a KTP-532 Laser and adjunctive treatment with excellent
      results over a 12 month follow-up period.

PMID- 23120300
TI  - Auricular trauma and its management.
AB  - Forty cases of external ear trauma have been studied during a period of three
      years from Jan '2001 to December 2004. It was observed that accidental trauma to
      the auricle may result in laceration, partial or complete loss of auricle. Injury
      of the tympanic membrane, temporal bone or facio maxillary region may be
      associated with auricular trauma. All wounds of auricle carry a risk of infection
      leading to perichondritis. Principles of successful treatment are conservation of
      tissue and prevention of infection.

PMID- 23120301
TI  - Percutaneous endoscopic gastrostomy (PEG) - An useful 'surgical' measure.
AB  - Eight patients were studied to evaluate the efficacy of a surgeonled percutaneous
      endoscopic gastrostomy (PEG). Three patients underwent PEG at the time of
      elective surgery (carcinoma larynx-2, carcinoma tonsil-1), two underwent
      placements during emergency surgery for neck trauma (blunt injury-1, penetrating
      injury-1) and three for palliation (recurrent tongue carcinoma-1, recurrent
      epilaryngeal carcinoma-1, metastatic neck nodes-1). For patients undergoing
      intraoperative PEG, the operative time was prolonged by an average of 12 minutes.
      There were no major procedural or feedingrelated complications in any of the
      patients. Individual subjective tolerability was good in all patients. A
      surgeonled PEG is a simple and safe means of combining all the advantages of
      enteral nutrition with none of the disadvantages of nasogastric tube feeding in
      emergency, elective head and neck operations and in palliation. The procedure
      merits wider use in head and neck surgery units in India.

PMID- 23120302
TI  - Role of technetium(99m) scan in detecting residual thyroid disease.
AB  - Technetium(99m) ((99m)Tc) Scintigraphy is a well established tool for diagnosing
      Thyroid disease. The purpose of this study is to evaluate the usage of this
      particular method in detecting residual thyroid disease after surgery and its
      role as a diagnostic marker for the work up of a patient with residual disease.
      All were female patients seen in the ENT OPD for a period of 1 year from Feb 2004
      Jan 2005, within the age group 24 yrs to 50 yrs.

PMID- 23120303
TI  - Repair of tympanic membrane perforation by topical application of 1% sodium
      hyaluronate.
AB  - OBJECTIVE: The administration of exogenous hyaluronic acid can increase the
      repair potential of damaged tissue. This study was conducted to verify whether or
      not the hyaluronic acid enhances the repair process in perforations of tympanic
      membrane. Hyaluronic acid is commercially available as its sodium salt. STUDY
      DESIGN: Thirty patients with dry central perforations of small or medium size (up
      to 3 mm) were treated locally with 1% sodium hyaluronate. The applications were
      repeated weekly for a maximum of five applications. RESULTS: It was found that
      treatment with sodium hyaluronate helps appreciably in the closure of tympanic
      membrane perforations and also that the scar formed in majority of them resembled
      the normal tympanic membrane. 86.67% (26/30) of the patients responded positively
      to the treatment. More importantly overall average percentage reduction in the
      size of perforations was 86.49%. CONCLUSIONS: It was concluded that topical
      application of 1% sodium hyaluronate can be an alternative to surgery in selected
      cases of tympanic membrane perforations.

PMID- 23120304
TI  - FNAC of salivary gland lesions with histopathological correlation.
AB  - HYPOTHESIS: Analysis of salivary gland lesions by FNAC and correlation with
      histopathology. To evaluate utility of FNAC in salivary gland lesions.Back
      ground: Salivary gland lesions form about 2-6.5% of all head and neck neoplasms
      in adults. They are easily accessible for FNAC (Fine Needle Aspiration Cytology)
      and risks of fistula formation or tumour implantation are low compared surgical
      biopsy. Also, cytology can provide a distinction between asalivary and non
      salivary lesion, benign and malignant lesions so also specific and non specific
      inflammation. METHODS: Seventy patients were studied prospectively over two
      years. FNAC was done using 10 cc syringes and 20-22 no. needle. Histomorphology
      was assessed on routine H & E (haemotxylin and eosin) stained paraffin sections.
      SPAS (periodic acid Schiff) and mucicarmine satins were also done. RESULTS: 80%
      of the lesions were neoplastic (61% benign, 31% malignant) and 20% were
      neoplastic. Pleomorphic adenoma was the most frequent benign neoplasm while
      mucoepidermoid carcinoma was the most frequent malignant lesion. Among the non
      neoplastic lesions, the maximum number of cases were of chronic sialadentis. In
      the present study, FNAC has a sensitivity of 94.54% and specificity of 80.95% for
      neoplastic lesions. CONCLUSIONS: FNAC was found to be a useful diagnostic tool in
      the evaluation of salivary gland lesions because of its simplicity, excellent
      patient compliance and rapid diagnosis. This cost effective tool is invaluable in
      planning the surgical management of the patient.

PMID- 23120305
TI  - Secretory otitis media: A school health survey.
AB  - The present study was carried out to find out prevalence of secretory otitis
      media in 200 school going children between the age group of 5-7 years by
      impedance audiometry besides clinical evaluation. 100 children were taken from
      two different schools catering to higher and lower socioeconomic strata of
      society. The overall prevalence of secretory otitis media came out to be 20.75%.
      It was 28.5% in lower socioeconomic group and, 13% in the other group. This high
      prevalence warrants routine screening for secretory otitis media. Further
      impedance audiometry was found to be very good method of screening secretory
      otitis media.

PMID- 23120306
TI  - Evaluation of improvement of hearing in type I tympanoplasty & its influencing
      factors.
AB  - study included 40 patients treated for CSOM with central perforation. Only type I
      tympanoplasty was done in 30 patients with dry central perforation and simple
      mastoidectomy with type I tympanoplasty was performed in 10 patients with moist
      or discharging perforation. Type I tympanoplasty utilizing an underlay technique
      with TFG shows high probability of success (85%). Presence of bilateral
      perforations lowers the success rate (66.66%). Status of non-operated ear is a
      significant factor for success rate. An overall hearing gain of about 10db was
      achieved. Poor pre-operative hearing status of elderly adversely influences post
      operative improvement of hearing. Typel tympanoplasty with simple mastoidectomy
      results excellent surgical success rate (100%) but gives less improvement of
      hearing (closure of A-B gap= 3.3db). In type I tympanoplasty alone surgical
      success rate drops to 80-75% but is offers more improvement of hearing (closure
      of A-B gap = 6.708 db).

PMID- 23120307
TI  - Masses of nasal cavity, paranasal sinuses and nasopharynx: A clinicopathological
      study.
AB  - An analysis of clinicopathological features of 240 cases presenting as mass in
      nasal cavity, paranasal sinuses and nasopharynx observed, both retrospectively
      and prospectively, over a period of 5 years in Jawaharlal Nehru Medical College.
      Aligarh. The incidence of masses in nasal cavity, paranasal sinuses and
      nasopharynx was 34.3 cases per year. Amongst the 240 cases studied, there were
      144 cases (60%) of non-neoplastic lesions, 56 cases (23.33%) of benign lesions
      and 40 cases (16.67%) of malignant lesions. All age groups were involved and the
      mean age of presentation with the increasing age were: - non-neoplastic (22.5
      years), benign tumors (26.8 years) and malignant tumors (35.3 years). The male to
      female ratio was 1.7:1 for non-neoplastic lesions; 3:1 for benign tumors: and
      2.3:1 for malignant lesions. In this study maximum number of cases were present
      in nasal cavity (65%) followed by paranasal sinuses (20%) and least number of
      cases involved the nasopharynx (15%). The relative number of non-neoplastic and
      neoplastic lesions varies from region to region. A provisional diagnosis was made
      after clinical assessment and radiological investigation but final diagnosis was
      made after histopathological examination.

PMID- 23120308
TI  - Interesting observations on Primary Atrophic Rhinitis.
AB  - Primary Atrophic Rhinitis (PAR) which has baffled the physicians of the past and
      the present ENT surgeons, till now, is found to have strong clinical evidence to
      suggest it to be of Hanseniatic origin. A rational review of literature,
      elicitation of the cardinal signs of leprosy - in its indeterminate
      paucibacillary form, and the similarity of the symptomatology between these two
      diseases corroborate this view. This is further sustained by observing it cured
      with antileprotic drugs which brings a new hope for these patients. It also
      unfolds a new horizon on further research on this disease.

PMID- 23120309
TI  - Physiological changes in ENT during pregnancy.
AB  - Although a number of changes occur in ear, nose, throat during pregnancy, yet
      these changes are neglected because majority of these changes go away after the
      pregnancy is over. Almost every corner of ENT is effected during pregnancy e.g.,
      ear, nose, larynx (voice), oesophagus, thyroid etc. This paper deals with the
      various physiological changes in ENT during pregnancy and the worsening of
      symptomatology of various ENT ailments during pregnancy. These physiological
      changes are mainly due to the changing levels of estrogens and progesterone
      hormones during pregnancy. Many of these changes lead to symptomatology referable
      to head & neck and various disorders managed by otolaryngologist are more
      prevalent during pregnancy. A thorough understanding of these various effects of
      pregnancy is mandatory for an otolaryngologist to treat these disorders.

PMID- 23120310
TI  - Role of grommet in otitis media with effusion: A necessity or nuisance? A
      comparative study.
AB  - Otitis media with effusion is one of the commonest otological problems in
      paediatric age group. The condition occurs in childhood as overt or covert
      hearing loss presenting as an educational or behavioural problem. As there is
      widespread controversy regarding its precise aetiology, natural history and
      pathogenesis a treatment dilemma still persists. The main goal of this study is
      to compare the efficacy of different modalities of medical and surgical treatment
      designed for this condition and analysis of the results statistical.

PMID- 23120311
TI  - Cholesteatoma, attic, ossicles.
AB  - Extension of cholesteatome in mastoid and middle ear occurs frequently. It is
      necessary to know the type of cholesteatoma extension and to decide the type of
      surgery to be done. The cholesteatome of the ear can extend to tie mastoid, attic
      and middle ear. Extension to intracranial region occurs in some cases but not
      discussed in the present review. Nowadays patients prefer hearing reconstruction
      even if only one ear is affected and the operation is modified accordingly.

PMID- 23120312
TI  - Unusual cervical mass - A surgical dilemma and unfortunate sequelae.
AB  - The differential diagnosis of a neck mass encompasses a broad range of
      possibilities including congenital cysts, inflammatory masses and both primary
      and metastatic neoplasms. A clear understanding of the normal anatomy of the neck
      and a high index of suspicion with a detailed history elicitation, proper
      physical examination and adjunctive test reports all lead to an accurate
      diagnosis. This is a case report of a thirty three year old lady who presented
      with a mass in the posterior triangle of neck with paraesthesia and mild weakness
      of the upper limb of the same side. The diagnostic evaluation revealed
      possibility of Schwannoma of the Brachial plexus and the surgical management
      posed a great surgical dilemma and led to cervical 5(th) and 6(th) trunk
      paralysis. We performed a second stage Sural nerve grafting.

PMID- 23120313
TI  - Sinus histiocytosis with massive lymphadenopathy.
AB  - Sinus Histiocytosis with Massive Lymphadenopathy is a very rare condition often
      presenting as neck swelling of unknown etiology. The disease involves extranodal
      sites in 20-30 percent of cases and histologically characterized by
      emperiopolesis, non-cohesive and non-epitheloid histocytes with abundant
      eosinphilic cytoplasm. An ideal treatment is yet to be established but here we
      present a short series of chemotherapy with alternating ABVD and COPD cycles
      giving satisfactory results.

PMID- 23120314
TI  - Unusual presentations of foreign body in aerodigestive tract.
AB  - Foreign bodies lodged in aerodigestive tract makes the commonest emergency in the
      otorhinolaryngology clinics. Diagnosis often becomes difficult with parental
      ignorance and lack of clear history. Patients with foreign body can have unusual
      presentations.

PMID- 23120315
TI  - A case of post traumatic retropharyngeal abscess.
AB  - Retropharyngeal abscess following blunt trauma neck is rare. We report one such
      unusual case which was drained surgically.

PMID- 23120316
TI  - Parapharyngeal second branchial cyst: A case report.
AB  - Branchial cleft cysts extending to the lateral wall of the pharynx are rare. An
      eight year old female child presented with a cystic swelling in the left parotid
      region. A bluish cyst was seen anterior to the anterior pillar of left tonsil. CT
      scan showed the cyst extending into left parapharyngeal space. External part of
      the cyst was excised via a transcervical approach and the internal part was
      marsupalised per orally.

PMID- 23120317
TI  - Angiolymphoid hyperplasia with eosinophilia - A case report.
AB  - Angiolymphoid hyperplasia with eosinophilia (ALHE) is a distinctive vascular
      tumor presenting as isolated or grouped papules or plaques or nodules over skin
      in head and neck. We, hereby, present a case of ALHE affecting the base of tongue
      a rare site of involvement.

PMID- 23120318
TI  - Kikuchi - Fujimoto disease.
AB  - Kikuchi - fujimoto disease also known as histiocytic necrotizing lymphadenitis is
      an idiopathic benign self limiting condition with a favourable outcome, usually
      affecting young women. The following cases have burn reported for clinical
      interest and for the rarity of the reports about this condition in ENT
      literature. In our series, we had 2 female patients aged 18 years and 25 years
      respectively and a male patient aged 45 years, presenting with fever, bilateral
      tender multiple cervical adenopathy including posterior triangle nodes not
      responding to routine antibiotics and anti-inflammatory drug treatment. ENT
      findings were within normal limits. Routine clinical investigations were within
      normal limits except for the raised ESR. Biopsy from one of the enlarged glands
      revealed necrotizing lymphadenitis. All the patients subsequently showed
      significant improvement locally in the neck and systemically without any further
      active treatment.

PMID- 23120319
TI  - Insular carcinoma of thyroid: A case report.
AB  - A histological distinct subset of thyroid carcinoma, which falls between well
      differentiated and anaplastic carcinoma with respect to cell differentiation and
      clinical behaviour. It has been categorized as poorly differentiated or insular
      carcinoma based on its characteristic cell groupings. Insular carcinoma warrants
      aggressive management with total thyroidectomy followed by radioactive iodine
      ablation of the residual deposit. We present a case of insular carcinoma, which
      was diagnosed post operatively based on the histopathological enzyme study.

PMID- 23120320
TI  - Sinonasal haemangiopericytoma.
AB  - Haemangiopericytoma is a rare vascular tumour accounting for about 1% of vascular
      tumours of the body. We report a case involving left maxillary region, its
      management along with review of literature.

PMID- 23120321
TI  - Esthesioneuroblastoma: A case report and review of the literature.
AB  - Esthesioneuroblastoma (ENB) is an extremely rare malignant neoplasm of the nasal
      cavity. We report the case of a middle aged man who presented with a 6-months
      history of progressive nasal obstruction, watering of the eye, headache and
      occasional epistaxis. A diagnosis of esthesioneuroblastoma was established by
      histopathology and confirmed by immunohistochemistry. On staging the mass was
      classified as a kadish stage C tumor. The mass was excised via a craniofacial
      resection through a bi-coronal approach and the tumor mass was peeled away
      completely from the frontal lobe dura. The patient underwent postoperative
      radiation, and he was free of recurrence at follow-up 3 months later.

PMID- 23120322
TI  - Deviated nasal septum in case of Klippel-Trenaunay-Weber Syndrome.
AB  - Klippel-Trenaunay-Weber Syndrome (KTWS) is a rare entity. It includes cutaneous
      hemangioma (Port-wine stains) of the face and extremities with associated
      varicosities and hypertrophy of underlying soft tissue and bone. Craniofacial
      involvement is rare in this syndrome. We report a case of Klippel-Trenaunay-Weber
      Syndrome who presented with craniofacial deformity leading to deviated nasal
      septum, nasal obstruction and intermittent nasal bleed. These patients can have
      involvement of oral cavity and nasal mucosa with angiomatous malformation, which
      can give rise to epistaxis and excessive bleeding during oral and nasal
      surgeries. We discuss the review and management of such cases from
      Otolaryngologists point of view.

PMID- 23120323
TI  - Tracheoesophageal fistula: New option in management.
AB  - Tracheoesophageal fistula is a life threatening condition. Patients not managed
      surgically ultimately die of their disease. Surgical management is the treatment
      of choice. We present a case of a patient that developed a tracheoesophageal
      fistula after tracheostomy. Surgical repair was done which failed due to
      infection. The patient was managed with the help of an esophageal stent and
      Trichloroacetic Acid cautery. This approach can be used in selected patients,
      depending upon the size and site of TEE Larger fistulae and those situated lower
      down e.g. supra carinal cannot be managed by this technique.

PMID- 23120324
TI  - An unusual sequel of submandibular gland calculus-A case report.
AB  - Sialolithiasis in sub-mandibular gland is a common condition. Sub-mandibular
      fistula as a sequel of sub-mandibular sialolithiasis is a rare entity. We report
      a case of an unusually large sub-mandibular gland calculus causing a cutaneous
      fistula.

PMID- 23120325
TI  - Spindle cell sarcoma of larynx.
AB  - Spindle cell carcinoma of larynx is rare tumors constituting only 0.6% of
      laryngeal neoplasm with predominance in elderly males (average 63 yrs). These
      tumors were described under various names: pseudosarcoma, Carcinosarcoma,
      fibromyxosarcoma, mixed sarcoma, polypoidal sarcoma. Immunohistochemistry and
      electron microscopy suggest that spindle cell carcinoma are true neoplasm and
      spindle cells are part of the neoplasm and not benign reactive fibroblast.

PMID- 23120326
TI  - Polymorphic reticulosis: A case report.
AB  - A 32 year old male came to us with right sided nasal obstruction, epistaxis and
      nasal mass. Biopsy confirmed the diagnosis of polymorphic reticulasis. which is
      infact malignant T cell lymphoma of the sinonasal region. The nasal T cell
      lymphoma causes slow progressive destructian of nose and midfacial region and
      still presents a diagnostic problem. The clinical and pathological
      characteristics and management of sinonasal lymphomas are discussed.

PMID- 23120327
TI  - A bullet in the maxillary sinus.
AB  - Maxillary Sinus is an unusual site for lodgment of foreign bodies. We present a
      rare case of impacted bullel in the right maxillary sinus which entered through
      the orbital floor which could be removed after using a nasal endoscope through a
      Caldwell luc approach.

PMID- 23120328
TI  - Hoarseness -As a presenting feature of aortic arch aneurysm.
AB  - Hoarseness due to left recurrent laryngeal nerve paralysis (LRLN) caused by
      identifiable cardiovascular disease is described as Ortner's syndrome or
      Cardiovocal syndrome. This was first described by Ortner in 1897 to describe left
      recurrent laryngeal nerve palsy secondary to Mitral Stenosis. The common
      conditions which gave rise to Ortners' syndrome include mitral stenosis, mitral
      valve prolapse, aortic aneurysm, septal defect, following cardiothoracic surgery,
      high altitude pulmonary hypertension, ductal aneurysm, aortic dissection etc.
      Herewith we are presenting an unusual presentation of Aortic arch aneurysm.

PMID- 23120329
TI  - Neuroendocrine carcinoma of supraglottis - A case report.
AB  - Neuroendocrine carcinoma of the larynx is a rare entity constituting about 0.6%
      of all laryngeal malignancies. An interesting case of neuroendocrine carcinoma of
      supraglottis in a 70 year old lady is being reported.

PMID- 23120330
TI  - Extranasopharyngeal angiofibroma arising from the infratemporal region.
AB  - Angiofibroma is a histologically benign but locally invasive tumour of the blood
      vessels characterized by architecturally irregular vessels set in a fibrous
      stroma. The commonest site for occurrence of these tumours in the body is the
      nasopharynx. It is rare to find extranasopharyngeal origin of angiofibromas. The
      infratemporal fossa is a very rare site of extra nasopharyngeal angiofibroma with
      only 4 cases reported in the literature. We report here a case of a vascular mass
      arising from the infratemporal fossa of a 13-year-old boy that was confirmed to
      be a case of angiofibroma histopathologically. A review is also made of the other
      reported cases of angiofibroma arising from the infratemporal fossa. The likely
      theory of origin of the tumour and its management is also discussed.

PMID- 23120331
TI  - Osteoma of the mastoid - A case report.
AB  - Osteoma of the mastoid is a rare, slow-growing and benign tumour. Normally it is
      asymptomatic, although it may cause cosmetic deformities most of the time. A case
      of osteoma of the mastoid in a 15 years old boy is reported here. Surgical
      removal was done for the cosmetic deformity. There was no recurrence during the
      two years follow-up period.

PMID- 23120332
TI  - A case of solitary fibrous tumour of the nose and paranasal sinuses.
AB  - Solitary fibrous tumours (SFT), formerly known as benign fibrous mesothelioma,
      are rare mesenchymal spindle cell neoplasms, originally described in the pleura,
      but now found to arise in many other locations such as mediastinum, urogenital
      tract, face, nose, paranasal sinuses, orbit, meninges, ear, buccal mucosa,
      tongue, salivary gland etc. It was first described as a distinct neoplasm in 1931
      by Klemperer and Rabin. On reviewing the literature, so far, 21 cases have been
      reported involving the nose and paranasal sinuses. A case of solitary fibrous
      tumour of the nose and paranasal sinuses is presented.

PMID- 23120333
TI  - Arteriovenous malformation and Color Doppler: posterior auricular artery.
AB  - Arterio-venous malformations (AVM) are rare in head and neck region and are
      generally arise from intracranial vessels. We present a case of spontaneous AV
      malformation in the post auricular region with posterior auricular artery as the
      feeding vessel that was diagnosed by Color Doppler sonography.

PMID- 23120335
TI  - Editorial.

PMID- 23120334
TI  - Hypopharayngeal carcinoma in a child: Case report.
AB  - A 15 years old boy with keratinizing squamous cell carcinoma of the Hypopharynx
      is being presented because of its rarity. The patient presented with pain in
      throat and difficulty in swallowing since 15 days. Barium swallow and direct
      Laryngoscopy revealed a mass in Hypopharynx. Tobacco smoking since early
      childhood can be the aetological factor. The patient did not consent for surgery
      and could not afford radiotherapy. Hence, Tracheostomy and feeding gastrosomy
      were done. Patient died at home two months after the diagnosis.

PMID- 23120336
TI  - Laryngeal thrush: Merf experience.
AB  - Fungal infection of the larynx is a relatively uncommon condition. The lesions
      max be confined to the vocal folds or may involve various other sites in the
      larynx. There is, invariably, a risk factor that predisposes to fungal infection
      viz. immune deficiency, inhaled or systemic steroids, antibiotic usage, etc.
      These lesions may mimic malignancy or a premalignant condition. There have been
      very few cases of laryngeal thrush reported in the literature. Awareness of this
      entity is essential because the management depends on an accurate diagnosis.
      These lesions invariably respond to a course of oral antifungal therapy and
      correction of risk factors. We report 3 cases of laryngeal thrush.

PMID- 23120337
TI  - Nasal mucociliary clearance in health and disease.
AB  - "Standard saccharine test is used to detect nasal mucociliary clearance time in
      healthy individuals both adults and children. The length of the nose was measured
      radiologically and with the help of a soft malleable rubber catheter. For healthy
      individuals, mean nasal mucociliary clearance lime is 8.2 minutes in children and
      9.5 minutes in adults. The mean nasal mucociliary clearance rates were 11.1
      mm/min for children and 12.7 mm/min for adults.Deviated nasal septum, chronic
      sinusitis, allergic rhinitis, atrophic rhinitis, chronic smokers and patients
      with recent nasal packings were taken as diseased conditions in adults, whereas
      children with adenoid hyperplasia were taken for the study. In all of these,
      nasal mucociliary clearance was significantly prolonged."

PMID- 23120338
TI  - Role of Bupivacaine in reducing post tonsillectomy pain.
AB  - Pain following tonsilleclomy is of major concern to both the surgeons and the
      Anesthesiologists. Pre-incisional Bupivacaine infiltration into the tonsillar
      fossa has been used as a method of relieving post-operative pain in children. In
      this study pre-incisional Bupivacaine infiltration into the tonsillar fossa
      resulted in immediate post-operative pain lasting four to six hours.

PMID- 23120339
TI  - Foreign body inhalation in children: Decisive factors for carrying out
      bronchoscopy.
AB  - Inhalation of Foreign Body is one of the most common causes of accidental death
      at home in the paediatric age group. There may not be a clear history of foreign
      body inhalation and the patient may be asymptomatic at initial presentation. This
      coupled with the failure of radiological investigations on most occasions makes
      this a vexing clinical situation. These apparently normal children almost
      invariably have a bad prognosis if the foreign body is ignored. This study aims
      to define the most important factors influencing the decision to carry out the
      definitive surgery, i.e., bronchoscopy, which can be diagnostic as well as
      therapeutic, based on our experience with 50 cases of suspected FB in the
      tracheobronchial tree from January 2001 to July 2003. Results from the study
      suggest that radiological investigations have only limited value in deciding the
      management of a patient with suspected Foreign Body inhalation. This should not
      influence the decision to carry out a bronchoscopy, which should rather be based
      on history and clinical examination.

PMID- 23120340
TI  - Auditory brainstem responses in neonatal hyperbilirubinemia and effect of
      therapy.
AB  - Objectives; To determine the effect of neonatal hyperbilirubinemia on auditory
      brainstem responses (ABRs) and evaluate ABR responses to lowering of bilirubin
      levels. STUDY DESIGN: prospective case control trial SETTING: tertiary referral
      center. PATIENTS: 60 neonates (40 cases & 20 controls). Term appropriate for
      date(AFD) neonates with uncomplicated birth history and bilirubin level of >= 13
      mg/dL were included as cases, those with bilirubin value of < 13 mg/dL were taken
      as controls.Interventions; First BERA examination was carried out within 24 hrs
      of the diagnosis of hyperbilirubinemia and repeat examination was done when total
      serum bilirubin came down to < 13 mg/dL with treatment. Comparisons were made
      between cases (before & after therapy) and controlResults; No abnormality in
      neonates with bilirubin < 18 mg/dL. Abnormal ABRs were observed in 24(60%) of the
      40 cases studied, with therapy it reverted back to normal in 15(62%). The
      commonest abnormality noted was prolonged latency of wave V(42.5%), followed by
      prolonged latency of wave III(35%) and wave I(22.5%). Prolonged latency of wave I
      was found in only those with bilirubin > 20mg/dL. Inter peak latency of wave IV
      (Brain stem conduction time) was prolonged in 8 cases; it reverted to normal in
      all cases. Prolonged inter peak latency of wave I-III was observed in 7 cases, of
      which it reverted to normal in 6. Absent waves reappeared in 4 out of 5 cases,
      but abnormal amplitude ratios reverted to normal in only one of the 7 cases in
      which it was abnormal.Conclusions; about 60% of term A FD neonates with serum
      bilirubin of > 18mg/dL will demonstrate ABR changes. Most of these changes revert
      to normal early after therapy, indicating need for aggressive therapy in this
      subgroup of neonates.

PMID- 23120341
TI  - Neoplastic diseases of the head & neck in children.
AB  - Pediatric neoplasm is next only to trauma as the most common cause of death. The
      cervicofacial malignancies presents a unique challenge owing to potential adverse
      effects of both the disease process and the treatment employed on critical
      developing head and neck structures.This study comprised of 106 children below 12
      years age group conducted during 1999-2003 at JNMC, Aligarh. Of 106 cases 70 were
      benign neoplasms and 36 malignant neoplasms. Nasopharynx was the commonest site
      of involvement. Nasopharyngeal angiofibroma was the commonest benign tumour and
      lymphoma was the commonest malignant neoplasm. Team approach is required for
      mitigation of the disease process.

PMID- 23120342
TI  - Alar base resection - Medial flap technique.
AB  - The primary goal of alar base resection is the narrowing of nasal base while
      preserving or recreating normal contour. The standard wedge resection, as
      proposed by Weir, does narrow the base but too open at the expense of normal
      appearing nostrils. 25 patients were taken up for corrective septo-rhinoplasty of
      which 5 patients needed alar base resection. The medial flap technique as
      proposed by Jack Sheen was adopted and normal appearing nasal base achieved in
      all cases.

PMID- 23120343
TI  - An epidemiological study on patients undergoing dacryocystorhinostomy.
AB  - Dacryocystorhinostomy is performed in patients with naso-lacrimal duct
      obstruction to bypass the site of obstruction so as to relieve the patient of the
      irritating and socially embarrassing symptoms of epiphora. We discuss the various
      epidemiological aspects especially the vast difference by which the females out
      number the males in patients undergoing DCR and the likely explanations for this
      difference in our study on 74 patients which underwent DCR in our institute.

PMID- 23120345
TI  - Rhinoplasty and young's operation in atrophic rhinitis.
AB  - Rhinoplasty in atrophic rhinitis is a difficult surgery because the dorsal skin
      is adherent to the underlying structures. There is also more chance of
      postoperative injection. Our experience of various types of rhinoplasly in 25
      atrophic rhinitis patients are presented here. The patients were from the age
      group 16 to 35 years. Most of the operations were done under local anaesthesia.
      Commonest graft used was conchal cartilage. Bone graft was avoided for
      augmentation because of its high rate of absorption in atrophic rhinitis. In 10
      patients Young's operation was done in one side along with rhinoplasty. Young's
      operation was done only with skin layer.

PMID- 23120346
TI  - Non surgical management of cystic lymphangioma.
AB  - Aim/Purpuse: To evaluate our experience of 19 patients of lymphangioma who were
      treated by intralesional Bleomycin. MATERIALS AND METHODS: Nineteen patients of
      lymphangioma aged between 16 days to 11 years were managed in the department. The
      male-female ratio was of 2:1. Commonest sites were in the neck (58%) followed by
      axilla (21%). The patients were treated by intralesional bleomycin injection.
      Bleomycin was given at a dose not exceeding 0.5 unit/kg/dose at interval of 2
      weeks. Reduction in size of the mass was noted in between 2 weeks to 16 weeks and
      number of injections required for each patient varied from 1 to 6. Follow up
      ranged from 1- 7 Year. RESULT: In injection group, significant reduction of mass
      was noted in 84% (n=l6) and 57% (n=11) of them showed complete disappearance. No
      serious complications were noted in any patient. CONCLUSION: Our experience
      showed that Bleomycin in aqueous solution is a good sclcrosing agent in the
      management of lymphangioma.

PMID- 23120347
TI  - Voice prosthesis - Our experience.
AB  - Malignancy of the larynx is a large group of malignancies in our country. The
      advanced stage of laryngeal carcinoma requires total laryngectomy which results
      in loss of speech along with other psychological and functional damages.
      Following total laryngectomy, tracheo-oesophageal voice prosthesis offers the
      most reliable form of voice rehabilitation. At S.M.S. Medical College and
      Hospital, Jaipur 25 patient underwent speech rehabilitation with voice prosthesis
      between Dec. 2001 to Dec. 2003. Speech rehabilitation was successful in all
      patients with few problem associated with indwelling prosthesis.

PMID- 23120348
TI  - Chemoradiotherapy for advanced head and neck cancer - Analysis of a prospective,
      randomized trial.
AB  - OBJECTIVE: To study the efficacy of neo-adjuvant chemotherapy followed by
      radiotherapy in advanced head and neck cancer. STUDY DESIGN: Randomised,
      prospective study. SETTING: Tertiary academic referral center. PATIENTS: One
      hundred and eighty patients of advanced head and neck squamous cell carcinoma.
      INTERVENTION: PATIENTS were randomized into two arms. The study arm (CT-RT arm)
      received 3 cycles of anterior chemotherapy with Inj. Cisplatin 100 mg/m(2) on
      D(1) and Inj 5F.U. 700 mg/m(2) on D(1)-D(4) at an interval of 21 days, followed
      by external radiation. The control arm (RT arm) received external radiotherapy
      only. The dose of Radiotherapy was 64 to 68 Gy in conventional fractionation.
      RESULTS: PATIENTS of CT-RT showed better tumour control locally than patients who
      received only RT. Toxicities were commoner in CT-RT arm but they were manageable.
      5 year survival is higher in the CT-RT arm (21% vs 16%; p value> 0.05).
      CONCLUSION: Anterior chemotherapy with Cisplatin and 5F.U. is associated with
      good clinical response which is translated into increased survival along with
      acceptable toxicities.

PMID- 23120349
TI  - Direct laryngoscopic observations in progressive hoarseness of voice.
AB  - Hoarseness is a common disorder of voice which indicates abnormality at the level
      of glottis. We present our study of forty cases of progressive hoarseness of
      voice who underwent direct laryngoscopy during a period of January 2003 to
      January 2004 in our hospital. The observations were recorded und the data was
      evaluated.

PMID- 23120350
TI  - Use of mitomycin C in endo-DCR.
AB  - OBJECTIVE: To evaluate the role of topical Mitomycin C in Endoscopic
      Dacryocystorhinostomy (DCR), for the prevention of stomal stenosis. PATIENTS:
      Thirty patients undergoing endoscopic DCR for chronic dacryocystitis were studied
      prospectively. The follow up period was 12 months. TECHNIQUE: PATIENTS were
      divided into two groups randomly. All of them underwent endoscopic DCR. One group
      was subjected to topical Mitomycin C application after surgery while the control
      group was not. MAIN OUTCOME MEASURES: Postoperative relief of epiphora and
      endoscopic documentation of the patency of the stoma were the main outcome
      measures. RESULTS: 80% cases of the Mitomycin C group and 86.67% cases of the non
      Mitomycin C group had long-term successful results. This result is not
      statistically significant (p> 0.2). CONCLUSION: Intraoperative Mitomycin C
      application does not alter the long-term results in endoscopic DCR. A properly
      and adequately performed surgery is more vital for successful result.

PMID- 23120351
TI  - Litigation suits in otorhinolaryngology - Areas of concern.
AB  - The factors that separate an otolaryngology related law suit from others are
      manifold. The definition of standard of care, the patient's expectation of a
      surgical outcome and the psychological consequence that results from the surgical
      complications are unique to this specially. As this specially deals with one of
      the most sensitive part of a human body, patient's expectations of any treatment
      is bound to differ from that of the doctor. Unlike other fields, the definition
      of standard of care is constantly evolving due to continuous introduction and
      modification of the techniques and instruments. Statistics shows that the most
      common allegation in law suits relating to this branch is inadequate consent for
      the proposed treatment followed by wrong techniques used for operation.
      Negligence in postoperative care, failure to diagnose early and faulty
      maintenance of medical words are the other major areas that concern a doctor in a
      court room. The present article aims at reviewing some major problem areas and
      addressing the legal aspects concerning those areas.

PMID- 23120352
TI  - Odontogenic Keratocyst of mandible.
AB  - The Odontogenic Keratocyst is a developmental odontogenic cyst and deserves
      special attention because of its peculiar histopathologic features and biologic
      behavior. It is believed that the Odontogenic Keratocyst arises from the
      proliferation of remnants of dental lamina. It is usually asymptomatic, and
      solitary lesion, however, it may be associated with Nevoid Basal Cell Carcinoma
      Syndrome. This work aimed to present a case of a very extensive Odontogenic
      Keratocyst in a 28-year-old woman.

PMID- 23120353
TI  - Laryngeal cyst- case report.
AB  - Laryngeal cysts are rare, generally benign lesions which can affect all age
      groups. We report a case of huge supraglottic cyst. A 19 years old female
      presented with hoarseness and airway obstruction secondary to large cystic muss
      involving the entire right side of supraglottis attached to right aryepiglottic
      fold. Cyst was dissected by laryngofissure approach. On regular follow up for 3
      years there is no recurrence of the lesion.

PMID- 23120354
TI  - Meningoencephalocele of the middle ear cleft: Three tier management.
AB  - Meningoencephalic herniation into the middle ear is a rare condition that can be
      life threatening for the patient due to eventual infective intracrunial
      complications. It is characterized by a bony and dural defect localized in the
      tegmen through which meninges and encephalic tissue can herniate.
      Meningoencephalic hernia of the middle ear can appear as an insidious
      complication of Chronic mastoiditis (infective) and its surgery, trauma or
      spontaneous. High resolution computed tomography (CT scan) and Magnetic resonance
      imaging (MRI) must be done to evaluate the extent and the contents of the
      disease. Early and effective surgical repair, the only appropriate treatment, is
      necessary to avoid complication and recurrence. Middle cranial fossa, mastoid,
      combined approaches and obliteration of mastoid; external auditory canal and
      middle ear are the surgical procedures for the repair of hernias. Various
      materials viz. fascia/ muscle/fat / cartilage/ bones/ synthetic materials are
      used. Recurrence of the repaired herniation has been reported. To overcome the
      problem of recurrence and have a foolproof method, a three tier management is
      described and suggested. ABSTRACT: Meningoencephalocele, brain hemiation.

PMID- 23120355
TI  - Crouzon syndrome: A case report and review of literature.
AB  - Crouzon syndrome, also called craniofacial dysostosis is an autosomal dominant
      disorder characterized by premature closure of cranial sutures, midfacial
      hypoplasia and orbital defects. Herein we report a case of this rare entity who
      presented with brachycephaly, maxillary hypoplasia, wide parrot beaked nose,
      repaired bilateral cleft lip and cleft palate along with dental and orbital
      abnormalities.

PMID- 23120356
TI  - Dentigerous cyst: A rare presentation.
AB  - Though Dentigerous cysts are encountered not so frequently by the
      otolaryngologist, a giant dentigerous cyst causing facial deformity and requiring
      a major reconstructive surgery is very rare. One such case is described.

PMID- 23120357
TI  - Disseminated Intravascular Coagulation syndrome - ENT surgeon's perspective.
AB  - ENT surgeon is seldom confronted with a systemic disease severe enough to
      progress to Disseminated Intravascular Coagulation syndrome (DIC), where he has
      to undertake a definitive surgical procedure for malignancy or perform an
      emergency tracheostomy. This calls for a judicious calculation of the pros and
      cons with an element of risk that needs to be accepted. We report two such
      patients who have been treated in such a scenario where the outcome varied
      depending on the severity and time of onset of the underlying coagulation
      disorder.

PMID- 23120358
TI  - Safety pin - The UNSAFE foreign body of air passage.
AB  - Foreign bodies in the air passage are familiar otolaryngological emergencies. The
      diagnosis and management in most cases is based on clinico-radiological findings.
      Here, we are reporting three cases of open safety pin at various locations in the
      respiratory tract i.e. in the nose, nasopharynx and larynx. Their clinical
      presentation and management are described in detail.

PMID- 23120359
TI  - A rare congenital anomaly of nose - Accessory nose : Case report.
AB  - We describe a 21 year old man who was found to have an opening on his external
      nose since birth. No other clinical and radiological abnormalities were
      demonstrable elsewhere in his body. The opening is on the lower part of the nose
      one cm. away from the midline on right side, clinically looking like a sinus.
      Histological examination of the excised tract showed an organoid structure that
      was consistent with an"Accessory nose."

PMID- 23120360
TI  - A case study of Plummer-Vinson syndrome.
AB  - The case series presents the pattern of association of different co-morbid
      conditions of Plummer Vinson's Syndrome. The commonest morbidity is web at post
      cricoid level. The symptoms of dysphagia are more common and there appears to be
      a female preponderance. The presenting age us usually 5th decade. Although
      association with post cricoid carcinoma has been reported but only 10% of cases
      in the present series had carcinoma at the time of presentation. The effect of
      iron and B-complex supplementation has been clinically appraised and good
      symptomatic relief has been seen. Maybe this measure can prevent the progression
      to malignancy. Bouginage was effective in relieving symptoms in all the cases it
      was tried.

PMID- 23120361
TI  - Fistula of submandibular gland-a rare presentation.
AB  - Salivary fistulas commonly affect parotid gland. Sabmandibular fistulas are very
      rare. Most of them are congenital in origin and may be associated with
      abnormalities of the branchial apparatus. Traumatic submandibular fistulas on the
      other hand are very rare entities with only few cases reported till date.

PMID- 23120362
TI  - Bronchial foreign body: A case report.
AB  - Exogenous foreign bodies in the tracheo bronchial tree, are not uncommon
      particularly in children. Children who are not given proper individual attention
      at an early age are more liable to ingest or inhale foreign body. Complications
      are related to site, size, shape, nature and duration of foreign body. Foreign
      body aspiration is associated with significant morbidity. Awareness of these
      possible complications and a high index of suspicion is the key to successful
      management. We report a case of bronchial foreign body in a 12 year old boy who
      had accidentally aspirated a metallic whistle. The foreign body was removed
      successfullv without any complications.

PMID- 23120363
TI  - Giant supraglottic schwannoma.
AB  - Schwannomas arising from the supraglottis are uncommon, if not rare. They are
      known to arise from the head and neck region but oropharyngeal presentation is
      not often seen. Few cases of pedunculated schwannoma arising from the
      aryepiglottic fold presenting as giant tumours in the oropharynx have been
      reported so far. The tumour in this case has been excised via intraoral approach,
      with nil residual morbidity. A follow up period of one year was uneventful
      without any recurrence.

PMID- 23120364
TI  - Lacrimal sac rhinosporidiosis.
AB  - Rhinosporidiosis is a disease caused by the organism Rhinosporidium seeberi,
      which is now believed to be a rare aquatic protistan parasite of fish. Ocular
      rhinosporidiosis is worldwide in distribution but relatively more common in India
      and Shrilanka. We report a retrospective case record of isolated lacrimal sac
      rhinosporidiosis in an 8 year male child from western Maharashtra. The clinical
      features, management and review of literature is discussed in brief.

PMID- 23120365
TI  - Nasopharyngeal carcinoma presenting as Gradenigo's syndrome.
AB  - Nasopharyngeal carcinoma usually has an insidious onset and non-specific features
      in the initial stages. This makes early diagnosis difficult. The most usual
      presenting features are cervical lymphadenopathy, otological symptoms (serous
      otitis media) and involvement of adjacent cranial nerves. We report a case of
      Gradenigo's syndrome in a patient of undifferentiated nasopharyngeal carcinoma.

PMID- 23120366
TI  - Macroglossia due to venous malformation.
AB  - Massive vascular malformation involving tongue can cause significant functional
      impairment. In this report we describe a rare case of extensive venous
      malformation involving tongue leading to obstructive sleep apnoea, inability to
      speak, eat, severe discomfort due to exposure induced dryness and ulceration.
      Multimodality treatment approach comprising of sclerotherapy, electrocautery and
      radiation therapy was used in this case.

PMID- 23120367
TI  - Lymphangioma tongue.
AB  - We present a rare case of Lymphangioma tongue which presented to us as
      macroglossia and wide excision of the lesion was done. We also reviewed the
      literature and an attempt to draw a meaningful conclusion regarding treatment has
      been done.

PMID- 23120368
TI  - Metastatic renal cell carcinoma presenting with epistaxis.
AB  - Renal cell carcinoma is a slow growing malignancy of the kidney that has a high
      propensity for metastasis. It is the most common metastasis reported in the
      paranasal sinuses. A fifty six year old male patient, an operated case of left
      renal cell carcinoma presented seven years later with epistaxis. Computerized
      tomography of the paranasal sinuses and of the abdomen showed a metastatic lesion
      involving the left nasosinus region and a lesion involving the right kidney with
      lung metastasis, respectively. Due to the poor prognosis palliative radiotherapy
      was given.

PMID- 23120369
TI  - A rare case of inflammatory pseudotumour of the submandibular lymphnode.
AB  - Inflammatory pseudotumour (IPT), also known as inflammatory myofibroblastic
      tumour, is a rare cause of benign cervical lymphadenopathy. In its acute clinical
      presentation it mimics malignant and infective causes of cervical
      lymphadenopathy. The combined clinical history, histopathological findings, and
      imaging features of an infiltrating soft-tissue mass should lead to the
      possibility of IPT. Radical surgery should be avoided before there is
      histological proof of a malignant tumor.

PMID- 23120370
TI  - Cyst vallecula unusual presentation.
AB  - Laryngeal cysts, particularly cyst vallecula are generally benign lesions which
      cause mild dysphagia or change in voice. We report here a case of cyst vallecula
      that caused soreness of throat, dysphagia and change in voice. A 22-year male
      presented with progressive dysphagia and muffled voice secondary to a large
      cystic mass involving entire vallecula and during coughing presented in oral
      cavity. Per oral marsupilization done and the problem resolved.

PMID- 23120371
TI  - Cancrum Oris: A case report.
AB  - Cancrum Oris is acute gangrenous stomatitis of oral and para-oral structures in
      age group between 2 to 16 years particularly in sub-Saharan Africa with high
      morbidity and mortality. Exact bacteriology is uncertain. Acute necrotising
      gingivitis and oral herpetic ulcers are considered to be antecedent lesions. The
      treatment of cancrum oris is penicillin, tetracycline, metronidazol and
      clindamycin. second step of management includes reconstructive surgery for the
      treatment of the functional and cosmetic problems. The authors are reporting a
      case of cancrum oris in a 1.5-year-old child.

PMID- 23120372
TI  - Nasal glioma : A case report.
AB  - Nasal glioma, also known as glial heterptopia or the occurrence of isolated non -
      leratomatous glial tissue is a rare and benign congenital defect. This condition
      is diagnosed usually at birth time and requires early treatment to prevent facial
      deformations. We report here a case of extranasal glioma that was diagnosed and
      treated at the department of ENT, Gandhi Medical College, Bhopal. We emphasize on
      the developmental theory proposed as the etiology and discuss the clinical
      aspects, treatment and follow up.

PMID- 23120373
TI  - Surgical management of glomus tympanicum tumor.
AB  - Glomus tympanicum tumor (also known as paraganglioma or chemodectoma) is the most
      benign tumor of temporal bone. Treatment may be palliative or curative.
      Palliative therapy includes watchful observation or radiotherapy and curative
      treatment is surgical. During 1995 to 2005, 18 cases of glomus tympanicum were
      managed at Basavanagudi ENT Care Centre Bangalore. We review retrospectively the
      diagnosis and surgical management of these cases. Advances in the imaging and
      refinements in traditional surgery have made correct diagnosis and complete
      excision of these tumors possible in most of the cases.

PMID- 23120374
TI  - External vs. internal osteotomy in rhinoplasty.
AB  - BACKGROUND: The aim of study is to compare the external osteotomy vs. internal
      osteotomy in patients undergoing rhinoplasty. METHODS: The study group comprised
      of 45 patients that had undergone rhinoplasty surgery. The 25 patients had
      undergone internal / endonasal continuous lateral osteotomy and 20 patients had
      undergone external / percutaneous perforating digital osteotomy. The internal
      osteotomy was done high to low to high using 4 mm. curved guarded osteotome. The
      external osteotomy was done by 2 mm sharp osteotome. The scoring system of Kara
      and Gokalan was followed for edema and ecchymosis. CONCLUSION: External osteotomy
      is an easy approach to carryout and makes fracture with high precision along
      preset lines. The bone stump is stable. The damage to the nasal mucosa is much
      less. There is reduced bleeding, reduced edema and reduced ecchymosis around
      eyes. The cutaneous scar at the entry site of osteotome is invisible.

PMID- 23120375
TI  - Ultrasonography a useful adjunctive in management of thyroid neoplasms.
AB  - Fine needle aspiration cytology has been the gold standard of diagnosis in case
      of thyroid neoplasm. However ultrasonography of thyroid neoplasm is a useful
      guide for an operating thyroid surgeon. We in our study evaluated patients of
      thyroid neoplasm with USG thyroid & studied its role in the therapeutic
      management of neoplasm. In our study of 10 patients of thyroid neoplasm we found
      USG of the thyroid neoplasm as a valuable guide in management.

PMID- 23120376
TI  - Comparative evaluation of Transient Evoked Oto-acoustic Emissions and Brainstem
      Evoked Response Audiometry as screening modality for hearing impairment in
      neonates.
AB  - OBJECTIVE: This study was designed to evaluate Transient Evoked Oto-acoustic
      Emission (TEOAE) as screening modality for hearing impairment in neonates.
      Brainstem Evoked Response Auditometry (BERA) was used as gold standard diagnostic
      tool in this study. The factors affecting the specificity of TEOAE were also
      studied. METHODS: The study group of 200 randomly selected neonates was subjected
      to TEOAE and BERA (400 ears). Oto-endoscopy was done in all TEOAE failures and a
      repeat test was done after suction cleaning of blocked external auditory canal
      (EAC). RESULTS: Otoscopic evaluation of all 52 TEOAE failures was done. EAC
      obstruction was noticed in 31 ears and 4 ears showed collapsible EAC. TEOAE was
      repeated after suction cleaning of the obstructed EAC and using long probe tips
      for collapsible EAC. This improved the Pass rate of TEOAE from 87% to 92%. EAC
      obstruction and collapsible EAC were the two factors identified in this study
      that significantly affected the specificity of TEOAE as a screening test. Pass
      rate of TEOAE in <48 hrs age group was found to be 55.5%, which was nearly half
      of over-all pass rate. This was because of high prevalence of obstructed EAC in
      this age group. TEOAE was found to be a rapid screening tool as average time
      taken for BERA was 35 min/neonate and for TEOAE was 17.4 min/neonate.
      Acceptability of TEOAE was found to be higher as compared to BERA. CONCLUSIONS:
      TEOAE is a simple and rapid test with relatively higher acceptability. But, the
      low sensitivity and specificity are the main shortcomings that take away from
      TEOAE, the status of independent screening modality for hearing impairment in
      neonates. TEOAE cannot completely replace BERA as screening modality for hearing
      impairment in neonates, however can complement it.

PMID- 23120377
TI  - Comparison of the efficacy of clinical examination, ultrasound neck and computed
      tomography in detection and staging of cervical lymph node metastasis in head and
      neck cancers.
AB  - There are many modalities, which are being used for detection of cervical lymph
      nodes in head and neck cancers clinical examination, computed tomography,
      ultrasound, magnetic resonance imaging and radionuclide scintigraphy. Various
      studies in past have highlighted their benefits and drawbacks used singly or in
      comparison with others. Here we present the study of 100 patients comparing the
      result of clinical examination, computed tomography and ultrasound.

PMID- 23120378
TI  - Lateral sinus thrombosis: A major problem still with us.
AB  - Twelve cases of lateral sinus thrombosis, which occurred as a complication of
      attico antral type of chronic otitis media, are reported. Management includes
      broad spectrum intravenous antibiotics and surgery. Radical mastoidectomy with
      incision of the lateral sinus and removal of its content was done for all cases.
      There were no deaths. The prognosis of lateral sinus thrombosis is good if
      treatment is instituted early with broad-spectrum antibiotics and surgery.

PMID- 23120379
TI  - Head and neck squamous cell cancer: Biology (1).
AB  - This review is the first section of tumor biology pertaining to head and neck
      squamous cell carcinoma (SCCHN). It is intended to introduce the basic concepts
      of cancer biology to enhance the translational research. The basic tumour biology
      relates to the aberrations in the normal cell cycle. cell growth and cell death.
      The genetic aspects of cancer focus upon the roles of oncogenes, tumor suppressor
      genes and stability genes. The epigenetic mechanisms of the cancer relates to DNA
      methylation and histone acetylation. This review, discusses the basics of these
      concepts.

PMID- 23120380
TI  - Single stage Delto-pectoral flap cover for large defects following extensive neck
      dissection.
AB  - Bulky neck nodal disease with involvement of the overlying skin develops large
      post resection defects with skin loss following extensive neck dissection, that
      may not be suitable for primary closure. We describe a simple and easy to do
      procedure for cover of such large post surgical resection neck defects by using
      the Delto-pectoral flap as a single staged procedure.

PMID- 23120381
TI  - Management protocols of Allergic Fungal Sinusitis.
AB  - Controversy surrounds the appropriate surgical approach and the appropriate
      medical therapy for Allergic Fungal Sinusitis. The present prospective study aims
      to assess the impact of these factors on the treatment outcome of Allergic Fungal
      Sinusitis. In the present study 34 cases with AFS were randomized into one of 3
      methods of post operative therapy i.e. systemic itraconazole (group A, n=11),
      topical steroids (group B, n=12) and nasal alkaline douches only (group C, n=11).
      Outcome was assessed at 6 months post-operative by the Kupferberg grading system
      for assessment of nasal and sinus mucosa. Grade '3' mucosal disease was defined
      as recurrence.Complete pre-operative opacification of sphenoid and frontal sinus
      was a predictor of poorer outcome. Postoperative systemic itraconazole therapy
      demonstrated a trend towards a better outcome but was not statistically
      significant. Larger trials are required to conclusively evaluate the merit of
      various post-operative treatment regimens for AFS.

PMID- 23120382
TI  - Spirometry as an objective tool for nasal patency.
AB  - Spirometry can be used as an objective tool for measuring nasal patency. it is
      sensitive, easy to perform, comfortable to patient The only limitation being that
      it only can be done in institution.

PMID- 23120383
TI  - Subselective embolisation in management of JNA.
AB  - Role of Embolisation in preoperative management of Nasopharyngeal angiofibroma is
      well established in present day therapeutic modalities. An improvised technique
      i.e., subselective embolisation has been provided by Interventional radiologists
      to fortify the therapeutic results. This study compares the final outcome of
      seven cases, four of which were embolised pre operatively. Each case was dealt
      with varying surgical approaches.

PMID- 23120384
TI  - Deep space infections of neck.
AB  - A retrospective study was performed on fourteen cases of deep cervical space
      infections in the neck admitted for diagnosis and treatment to the ENT
      Department, during a period of seven years from 1989-1997. Of the fourteen, four
      patients had Ludwig's angina and of the fourteen, one had a very serious
      complication resulting in death. Early diagnosis and adequate treatment were of
      paramount importance. The role of tracheostomy and management of airway in deep
      cervical space infections of the neck is discussed to gether with bacteriology,
      antibiotic treatment and surgical management.

PMID- 23120385
TI  - Salvaging vision in an extensive parameningeal rhabdomyosarcoma: A case report.
AB  - This communication presents a case report of a parameningeal rhabdomyosarcoma in
      a young male leading to vision loss which was effectively salvaged using prompt
      intervention in the form of surgery and high dose systemic steroids. Early
      debulking was the key in the prevention of complete blindness in our patient.

PMID- 23120386
TI  - Synovial sarcomna of larynx-a rare site.
AB  - Synovial sarcoma is a soft tissue sarcoma of unknown histiogenesis and occurs
      predominantly in the lower limbs of young adults and the head and neck is a
      relatively rare site, there are about 10 cases with laryngeal localization in the
      world literature. We present a 52 year old male with synovial sarcoma of larynx.
      Total laryngectomy was done and patient is free from disease till date.

PMID- 23120387
TI  - Silent intratemporal facial nerve schwannoma associated with Chronic Suppurative
      Otitis Media: A rare presentation.
AB  - Facial palsy is a common manifestation of intratemporal facial nerve schwannoma.
      Review of English literature describes intratemporal facial nerve schwannoma
      presenting as vertigo, tinnitus (without facial palsy) which were diagnosed on CT
      scan or MRI of temporal bone. We are presenting two cases of asymptomatic facial
      nerve schwannoma without facial palsy presenting only as Chronic Suppurative
      Otitis Media (CSOM), which were diagnosed incidentally during surgery.

PMID- 23120388
TI  - Isolated sphenochoanal polyp: A rare clinical entity.
AB  - Choanal polyps almost always appear as solitary growth and most commonly arise
      from the maxillary sinus. Isolated polyp originating from the anterior wall of
      the sphenoid sinus or from its interior and extending as choanal polyp in to the
      nasopharynx are extremely rare clinical entities. Here we report a 34-year-old
      male presenting with a history of headache, intermittent nasal discharge and
      nasal obstruction. A diagnosis of sphenochoanal polyp (SCP) was made on nasal
      endoscopy and magnetic resonance imaging. The SCP was removed endoscopically via
      a transnasal sphenoidotomy and histopathologically it was confirmed as
      inflammatory polyp. In this paper we discuss the clinical presentation and
      surgical management of this rare clinical entity.

PMID- 23120389
TI  - Heminasal aplasia: A report of two cases.
AB  - Heminasal aplasia is a rare congenital malformation. It is often associated with
      other malformations of the facial region, including abnormalities of the eye and
      lacrimal system, facial bone malformations and proboscis lateralis. We present
      two cases of heminasal aplasia, discuss their embryological basis and nasal
      reconstruction of the same.

PMID- 23120390
TI  - External rhinoplasty for dorsum swellings.
AB  - As any swelling over dorsum nose is cosmetically unacceptable so is the post
      operative scar. The external rhinoplasty approach proceeds in the natural tissue
      dissection planes in the nose, thus ensuring minimal bleeding, improved exposure
      and good healing with minimal scar formation. We present cases of three different
      swellings due to rhinophyma, dermoid cyst and a rare interesting foreign body all
      dealt with external rhinoplasty approach with good results.

PMID- 23120391
TI  - Unusual case of laryngeal foreign body.
AB  - The Foreign bodies in respiratory tract have been major cause of morbidity and
      present as challenge to otolaryngologists. Despite improvement in medical care
      and public awareness, they are major concern for otolaryngologists. The spectrum
      of presentation varies widely from sudden death due to respiratory obstruction to
      accidental finding during routine investigations. A case of unusual presentation
      of laryngeal foreign body with just loss of voice is described here.

PMID- 23120392
TI  - Oncocytic variant of a ductal retention cyst in the interarytenoid region.
AB  - Laryngeal cysts are a mixed group of benign lesions that have been classified as
      per their site of origin and histopathology. We report a case of an
      interarytenoid cyst in a 56 year old male with hyperparathyroidism. The cyst was
      resected under an operating microscope using KTP532 laser. It was reported on
      histopathology as an oncocytic variant of a ductal retention cyst.

PMID- 23120393
TI  - Kawasaki disease (syndrome)-our experience-.
AB  - Kawasaki disease also known as mucocutaneous lymph node syndrome is a generalised
      vasculitis of unknown etiology. Presenting a review of the literature and using
      our cases for illustration we discuss some of the pertinent features in the
      evaluation and management of patients with this condition. 2 cases of Kawasaki
      disease have been evaluated and treated in the department of ENT and Paediatrics
      who responded satisfactorily to treatment with I.V.Immunoglobulin and Aspirin.
      The case reports have been presented in view of the rarity of reporting of
      similar cases in India and the need for early diagnosis and prompt treatment to
      prevent coronary artery aneurysm and other serious complications.

PMID- 23120394
TI  - Primary mucosal malignant melanoma of middle ear - A case report.
AB  - Primary mucosal malignant melanoma reported in this case is a rare clinical
      entity. Very few cases of primary mucosal malignant melanoma of middle ear have
      been reported in the literature till date. The etiopathology, clinical features
      and management of this disease has been described here.

PMID- 23120395
TI  - Adenoid hypertrophy presenting with systemic hypertension.
AB  - A two and half year old male child was seen with systemic hypertension, left
      ventricular dysfunction, mitral regurgitation and congestive cardiac failure.
      Examination revealed adenoid hypertrophy. He was also suffering from obstructive
      sleep apnea. He was being treated with anti-hypertensive and anti-failure drugs.
      Adenoidectomy was performed following which obstructive sleep apnea symptoms
      disappeared and his cardiac status improved markedly. Subsequently he was weaned
      off anti-hypertensive and anti-failure therapy.

PMID- 23120396
TI  - Changes in UK ORL-HNS training scheme: Does the Indian trainee have a place
      anymore?
AB  - The determination of the UK Government to modernise medical careers, the shortage
      of training jobs for local medical graduates, the establishment of the
      Postgraduate Medical Training and Education Board (PMETB) and European Union
      rules have combined to change the scheme of surgical training in the United
      Kingdom. In the opinion of the author, the Indian Otorhinolaryngological (ORL)
      trainee can no longer aspire to reasonable higher training in the UK.

PMID- 23120397
TI  - Malignant melanoma of the nasal cavity-A case report.
AB  - Mucosal melanoma of the nasal cavity is a rare tumour. Here we have reported a
      case of 54-year-old male patient presented with the black mass coming out from
      right nasal cavity and occasional slight bleeding from the mass. The tumour was
      excised by lateral rhinotomy. The surgery was followed by radiotherapy.

PMID- 23120398
TI  - Benign osteoblastoma of maxillary sinus: A rare presentation.
AB  - Benign osteoblastoma of paranasal sinuses is a rare tumor of the 2(nd) decade of
      life with only few cases reported till date. It arises most commonly from the
      ethmoid sinus and present as an intra-nasal mass leading to broadening of the
      nasal bridge. Here we present a case of benign osteoblastoma in a 8 year old girl
      presenting with a large intranasal mass seen through nostril and leading to
      facial deformity.

PMID- 23120399
TI  - Lipoma of tongue - A rare site for a rare site for a common tumour.
AB  - Lipoma is the commonest benign tumour occurring at any anatomical site where fat
      is present. In oral cavity and oropharynx it is a relatively uncommon neoplasm..
      Tongue which is totally devoid of fat cells is also a site for lipoma albeit very
      rarely. This is one such rare case of the universal tumour, presenting at the
      lateral margin of the tongue, for which complete tumour excision was done.

PMID- 23120400
TI  - Unusual case of laryngeal lipoma.
AB  - Lipomas are benign tumors, composed of fat cells of the adult type. While lipomas
      on the trunk and limbs are common, they are rare in the upper aerodigestive
      tract. Here we report a case of laryngeal lipoma presented with a complaint of
      change of voice.

PMID- 23120401
TI  - Primary nasal Tuberculosis - A case report.
AB  - During the past two decades, Tuberculosis - both pulmonary and extrapulmonary
      have re-emerged as a major health problem worldwide. Nasal tuberculosis may be
      primary, or secondary to pulmonary tuberculosis or facial lupus. However all of
      them are rare entities. Nasal tuberculosis should be considered in the
      differential diagnosis of chronic nasal granulomas. We report a case of primary
      nasal tuberculosis in an adult female who presented with a polypoidal lesion in
      the nasal cavity. The diagnosis was based upon smear study, histopathology,
      culture & polymerase chain reaction. The patient successfully responded to
      antituberculous therapy and is presently disease free. Given the resurgence of
      tuberculosis in recent times, it is important that otolaryngologists remain aware
      of this rare clinical entity.

PMID- 23120402
TI  - An interesting case of arterio-veinous malformation in the neck.
AB  - An arterio-veinous malformation can be acquired and is rarely congenital. It
      usually presents with cosmetic deformity. If large it may manifest features of
      haemodynamic changes. Clinical assessment is the mainstay of diagnosis.
      Arteriography, MR angiography and rarely histopathology may help in clinching the
      final diagnosis. It is treated with wide excision after ligation of feeder
      vessels. Herein we present one such case of arterio-veinous malformation with
      review of available literature.

PMID- 23120403
TI  - Spreader graft in septo-rhinoplasty.
AB  - BACKGROUND: The aim of study was to evaluate the effects of spreader graft in
      septorhinoplasty. MATERIALS AND METHODS: The study group comprised of 33 patients
      of various nasal deformities who underwent consecutive septorhinoplasty at Asan
      Medical Center, University of Ulsan, College of Medicine, Republic of Korea
      (South Korea). All the patients had undergone open rhinoplasty procedure. The
      submucous resection of septum was done, leaving 1 to 1.5 cm. of septal cartilage
      for dorsal and caudal support. The spreader graft was harvested from septal
      cartilage in 31 cases and costal cartilage in 2 cases. All the patients had
      undergone endonasal high to low to high osteotomy, paramedian osteotomy and
      percutaneous transverse osteotomy.The periosteum was not elevated in any case.
      The spreader graft was placed and secured with septal cartilage and upper lateral
      cartilage with suture material. Crushed small pieces of septal cartilage were
      used for dorsal augmentation. The tutuplast fascia lata was used to camouflage
      the dorsal irregularity. CONCLUSION: All the cases had good aesthetically dorsal
      line, opening of internal nasal valve area and good septal support, which was
      weakened by the removal of deviated septum.

PMID- 23120404
TI  - Surgical repair of postlaryngectomy pharyngocutaneous fistulas.
AB  - Pharyngo-cutaneous fistula is a common complication after laryngectomy, which
      increases both the morbidity and the hospital stay. The incidence rate varies
      from 8.7% to 24.8% in different institutions. The continuous salivary leak is
      very much troublesome for the patients. There are various predisposing factors
      out of which preoperative radiotherapy, diabetes, malnutrition is very important.
      Spontaneous closure occurs in most of the cases on conservative management and
      only a few need surgical closures. Surgical methods used are direct surgical
      repair in two layers inner mucosa and outer skin, single distant flap like DP or
      PMMC, double distant flap like DP and PMMC one for inner mucosa and another for
      outer skin. Post operative swallowing was satisfactory in all the cases and there
      was no recurrence of fistula in one and half year follow up.

PMID- 23120405
TI  - Laser assisted uvulopalatopharyngoplasty.
AB  - LASER is acronym for Light Amplification by Stimulated Emission of Radiations.
      Medical laser technology has revolutionized the way surgeries are being done. As
      laser provide exceptional benefits to the patients it is also called-"A BEAM OF
      LIGHT FOR THE BENEFIT OF MANKIND". Carbon-dioxide laser is used to excise and
      vaporize tissue. Surgical injury to the tissue is determined by the power density
      and spot size. Vaporization is carried out in the defocused mode while cutting or
      excision is done in focused mode. Laser is being used in almost all parts of the
      human body. Laser surgery has become the choice of millions world over as it
      provides exceptional benefits not only to the patients but also to the surgical
      community. In the last seven years, 195 patients suffering from obstructive sleep
      apnea syndrome were subjected to Laser Assisted Uvulopalatopharyngoplasty (LAUP).
      Trimming and reshaping of the Uvula and Palate is done as outpatient. It is like
      a visit to a dentist. It takes 10-15 minutes per session. The procedure is
      repeated 3-4 times. Sittings are spaced about 3-4 weeks apart. The patient can go
      back to work the same day.

PMID- 23120406
TI  - Rhinocerebral mucormycosis: A deadly disease on the rise.
AB  - According to WHO, there will be epidemic of diabetes world over and India is
      going to be 'A diabetes capital of the world' by 2025. With the increasing
      incidence of diabetes, the associated complications are also bound to increase.
      Rhinocerebral mucormycosis is one of them.Rhinocerebral Mucormycosis is an
      opportunistic, fulminating fungal infection, caused by Rhizopus species of order
      of mucorales, frequently seen in diabetic and immunocompromised patients.
      Mucormycosis has a very high mortality rate.Early diagnosis and treatment with
      Amphotericin-B is the key to combat this disease successfully. We have seen 13
      cases in last 3 years (2002-2005) in our area. This incidence is significant, as
      this type of cases were rarely seen before 2002, in this geographical area. We
      present an account of these cases; treatment strategies adopted, review of
      literature, and highlight 'the role of ENT surgeon in diagnosis and management of
      this dreadful disease'.

PMID- 23120407
TI  - Comparative study of underlay tympanoplasty with temporalis fascia and tragal
      perichondrium.
AB  - The perforations of the tympanic membrane maybe of traumatic origin or due to
      chronic suppurative otitis media. If the perforations fail to heal
      conservatively, they require surgical closure. Autologous graft materials have
      stood the test of time in repairing tympanic membrane perforations. In our
      tertiary care institution we conducted a prospective randomized control trial on
      50 subjects to evaluate the comparative efficacy of temporalis fascia and tragal
      perichondrium as grafting material in underlay tympanoplasty. In this study
      surgical success was evaluated in terms of intact drum membrane during the follow
      up period and closure of A-B gap within 10 dB. Temporalis fascia achieved a graft
      uptake of 84% and a satisfactory hearing improvement in 76% of the patients.
      Tragal perichondrium achieved a success rate of 80% graft uptake and 75% hearing
      gain. The rates are comparable with no statistical significance of the difference
      between them.

PMID- 23120408
TI  - Rehabilitation of the tympanomastoid cavity in Canal Wall Down procedures.
AB  - During 1980 to 2004, 1602 Canal Wall Down (CWD) procedures was performed of which
      978 had primary surgery and 624 were revision cases. We have highlighted various
      methods for total clearance of disease process from the tympanomastoid area,
      making of a smooth cavity, augmentation of middle ear space for better functional
      results, inlay temporalis fascia grafting, ossiculoplasty with live tissue
      grafts, natural obliteration of the cavity and meatoplasty.Healing of cavity and
      tympanic membrane (TM) graft was achieved in 1548 (94.2%) of cases. Revision
      surgery was performed in 32 cases for recurrence or residual cholesteatoma,
      mostly in the attic and middle ear. Persisting discharge was present in 12 cases.
      Serviceable hearing (airbone (A-B) gap closure up to 20 dB) was achieved in 1017
      (63.5%) cases. Hearing was worse than pre-operative level in 154 (9.6%) cases.
      There was no improvement in hearing in 397 (24.8%) cases. Serviceable hearing was
      obtained after second stage ossiculoplasty in 34 (2%) cases.

PMID- 23120409
TI  - Role of lignocaine nebulization in post bronchoscopy patients-A study of 200
      cases.
AB  - Rigid Bronchoscopy is carried out for the diagnosis and removal of the foreign
      body. The post operative period may have complications like laryngobronchial
      spasm, laryngeal oedema, in turn may require tracheostomy and later on may lead
      to cardiac arrest and respiratory arrest. These post operative complications can
      be drastically reduced by the use of nebulization with the combination of
      steroids, Bronchodilators and lignocaine. Combination with lignocaine
      nebulization reduces rates of morbidity and mortality effectively then nebulizing
      only steroid and bronchodilators. Lignocaine reduces the irritative cough,
      reactive secretion and also hence bronchospasm and also vomiting.

PMID- 23120410
TI  - The investigation of bacteriology of chronic suppurative otitis media in patients
      attending a tertiary care hospital with special emphasis on seasonal variation.
AB  - BACKGROUND: Chronic suppurative otitis media takes a lot of time in the hospital
      outdoors and a considerable amount of O.T. timings. Chronic suppurative otitis
      media may be either active chronic otitis media or a sequel of previous otitis
      media. OBJECTIVE: (a) To understand the bacteriology of Chronic suppurative
      otitis media (b) Their susceptibility patterns to commonly used antibiotics in
      this age of emerging resistance (c) the seasonal variation in the bacteriological
      pattern (d) For better empirical treatment of C.S.O.M where culture facilities
      are not available so that both intracranial and extra cranial complications can
      be avoided. MATERIALS AND METHODS: The secretions of 160 samples belonging to
      various age groups and of both sexes of clinically proven chronic suppurative
      otitis media with definitive exclusion and inclusion criteria were collected and
      cultured by aerobic and anaerobic methods. Drug sensitivity was done according to
      standard laboratory protocols. A month wise visit of the patients has been
      recorded to note any seasonal variations in the isolates. RESULTS: The most
      common aerobic organism is Pseudomonas Spp and most common anaerobes isolated
      being Bacteriodes species. Their susceptibility patterns and seasonal variations
      have been discussed. CONCLUSIONS: It is observed that chronic suppurative otitis
      media affects mainly younger group of population, mostly (86.8%) below 40 years
      of age. Majority of them (31.9%) belonged to, 10-19 years of age. The most common
      isolate being Pseudomonas Spp. (64.4%) followed by Staphylococcus aureus (33.8%).
      In the anaerobic group (1.8%) the Bacteriodes species is most prevalent. The most
      effective antibiotic in the aerobic isolates is Amikacin followed by Gentamicin
      and Cefotaxime where as for anaerobic isolates Cefoperazone sodium has better
      sensitivity. The isolation rates of both aerobic and anaerobic groups of
      organisms are more in the month of July to September, which is the monsoon season
      in this place. Isolation of Pseudomonas Spp. in Monsoon and post monsoon season
      may have been due to filling up of water bodies with rain water and infection
      with an omnipresent saprophytic organism like Pseudomonas Spp.

PMID- 23120411
TI  - Effect of functional endoscopic sinus surgery in patients of chronic sinusitis
      with bronchial asthma.
AB  - Rhinosinusitis and bronchial asthma have been found to be coexistent in different
      studies. A prospective study of 23 patients with bronchial asthma who underwent
      Functional endoscopic sinus surgery (F.E.S.S) for coexistent chronic sinusitis
      was undertaken and the effect of endoscopic sinus surgery on bronchial asthma was
      analyzed in these patients using both subjective and objective criteria. It is
      concluded in this study that Functional endoscopic sinus surgery for chronic
      sinusitis in cases of bronchial asthma helps in reduction of their asthma
      symptoms, requirement of medication and helps in improving their peak expiratory
      flow.

PMID- 23120412
TI  - Impact of nasal polyps on quality of life of chronic sinusitis patients.
AB  - OBJECTIVE: To study the significance of nasal polyps on the symptoms of chronic
      rhinosinusitis (CRS) and their influence on surgical outcomes. METHODS:
      Retrospective analysis of prospectively collected data comparing two groups of
      patients diagnosed with CRS with and without polyps who underwent surgery with a
      minimum of 3 month follow up period. Subjective scoring was performed using the
      Sino-nasal Outcome Test (SNOT-20) questionnaire. Computed tomography (CT) scans
      were compared using the Lund-Mackay scoring system. Endoscopic findings were
      graded according to Lanza and Kennedy staging system. The two groups were
      analyzed for the need of revision surgery. RESULTS: 30 patients underwent
      surgical management of CRS over a period of one year. 20 were male, 10 were
      female and the average age was 26 years (range 15-55years). Polyps were present
      in 15 patients with CRS while, the other 15 did not have polyps. The average CT
      score was 10.13 for the polyp group and 9.79 for patients without polyp.The Polyp
      group SNOT-20 preoperative scores averaged 20.27 with improvement to 3.80 at 2
      weeks, 2.67 at 1 month and 2.93 at 3 months (86.21% improvement p=0.001). Non
      polyp group SNOT-20 scores were 18.80 preoperatively with improvement to 4.67 at
      2 weeks, 3.40 at 1 month and 3.27 at 3 months (81.83% improvement). Preop
      diagnostic endoscopy on polyp group was 5.27 which improved to 2.13 in 2 weeks,
      1.33 in 1 month and 1.53 in 3 months (73% improvement). In the non polyp group it
      was 4.53 pre-operatively which improved to 1.20 in 2 weeks, 0.93 in 1 month and
      to 1.13 in 3months (69% improvement). 6 patients required revision surgery (20%),
      3 (10%) belonging to polyp group and 3 (10%) who did not have polyps. CONCLUSION:
      Nasal Polyp has a significant negative impact on the patients with CRS. Patients
      with polyps have higher symptom scores, worse objective findings compared with
      patients without polyp, but patients with polyp show more improvement after
      surgical intervention and need for revision surgery is equal in both groups.

PMID- 23120413
TI  - Rhinosporidiosis: Its varied presentations.
AB  - Rhinosporidiosis is the fungal infection generally affecting the nasal mucosa. In
      this article we are presenting two unusual cases of rhinosporidiosis. First case
      presented with nasopharyngeal mass, without any past history of bathing in
      stagnant water or epistaxis. Mass was excised using nasal endoscope. Second case
      presented with recurrence of rhinosporidiosis even after nine times surgical
      intervention with systemic Amphotericin-B. In this patient, surgical excision of
      mass was assisted with Amphotericin-B nasal douching and oral Itraconazole. Both
      patients are doing well with no recurrence till date.

PMID- 23120414
TI  - Solitary fibrous tumor of the infratemporal fossa: A case report.
AB  - First described as a pleural neoplasm, the solitary fibrous tumor (fibrous
      mesothelioma) has been reported in a number of extrapulmonary sites, including
      the Head-Neck region. In the Head-Neck region, it has been described in the
      sinonasal tract, epiglottis, parapharyngeal, retropharyngeal spaces, parotid and
      infratemporal fossa. We present the second case of solitary fibrous tumor of
      infratemporal fossa described in world literature. A complete excision was
      achieved by transmaxillary approach.

PMID- 23120415
TI  - Sinonasal teratocarcinosarcoma-A case report.
AB  - Sinonasal teratocarcinosarcoma is a very rare tumor of ambiguous origin. Detailed
      examination of the biopsy material is essential for diagnosis. It is a very
      aggressive tumor with a five-year survival rate of 45%. Surgery with radiotherapy
      has been shown to be effective. We report a case of a 38-year old Indian
      gentleman with left nasoethmoidal mass eroding the cribriform plate with
      intracranial extension. Subtotal endoscopic excision of the mass revealed
      features of a sinonasal teratocarcinosarcoma. Immunohistochemistry confirmed the
      same. The patient was subsequently treated with radiotherapy. The clinical
      features, histopathological and immunohistochemistry findings and management of
      sinonasal teratocarcinosarcoma are discussed.

PMID- 23120416
TI  - Nasopharyngeal glioma: A unique presentation in infants.
AB  - Despite the complex embryological development of the nose and surrounding
      structures, significant developmental nasal anomalies are rare. Of the various
      anomalies like-nasopharyngeal cysts, hairy polyps, dermoids, haemangiomata,
      fibromas, mucocoeles, lipoma, aplasias. We are presenting a rare case of
      Heterotopic Brain Tissue in the nasopharynx. This 1.5-month-old patient was
      operated through transpalatal route and mass excised. Histopathologicaly it
      consisted of various central nervous tissue elements. Seven months post surgery
      patient is thriving well.

PMID- 23120417
TI  - Primary thyroid tuberculosis.
AB  - In India, it is estimated that more than 40% of the adults are infected with
      tuberculosis bacilli and every year 2 million people develop tuberculosis and
      nearly 500,000 die from it1. But, tuberculosis of the thyroid gland occurs only
      rarely. Since extra-pulmonary tuberculosis is now seen relatively more
      frequently, the existence of this condition should be recognized when goitres are
      being treated. We present a case of right thyroid nodule associated with low
      grade fever and weight loss. No signs and symptoms of hypothyroidism or
      hyperthyroidism were present. Patient did not have any other tuberculosis focus.
      Routine investigation and chest X-ray were normal. Sputum for Acid Fast Bacilli
      was negative. Fine Needle Aspiration Cytology and Contrast Enhanced Computed
      Tomography led to a diagnosis of Primary Thyroid Tuberculosis in a euthyroid
      patient. Patient responded well to Anti tubercular Drug Therapy along with
      repeated aspiration.

PMID- 23120418
TI  - Fibrous dysplasia of Sphenoid bone.
AB  - Fibrous dysplasia represents a disturbance of normal bone development
      specifically a defect in osteoblastic differentiation and maturation that
      originates in the mesenchymal precursor of the bone. In fibrous dysplasia, the
      lesion expands, which leads to a distortion and weakening of bone. Although the
      lesion is not encapsulated, it tends to remain enclosed within a shell of
      cortical bone. This shell can be thinned as a result of the pressure exerted on
      it. As it slowly progresses, fibrous dysplasia can cause skeletal destruction and
      deformity.

PMID- 23120419
TI  - Teratoma tongue: Case report and review of literature.
AB  - Teratomas are true neoplasms composed of tissues from all three germinal layers
      and may exhibit variable levels of maturity. They have an unknown origin and
      eccentric microscopic appearance. Teratomas arising from the oral cavity are rare
      in the newborn; only 22 cases have been reported in the literature. We describe a
      female neonate with an oral teratoma originating from the tongue that was
      successfully treated with surgery.

PMID- 23120420
TI  - An atypical presentation of cavernous sinus thrombosis.
AB  - In a typical presentation of cavernous sinus thrombosis there are palsies of
      IIIrd, IVth and VIth cranial nerves along with disturbance of ophthalmic division
      (V1) of trigeminal nerve. In this manuscript we report a case of unilateral
      cavernous sinus thrombosis for its atypical presentation. Atypical features in
      this case were presence of ipsilateral lower motor neuron type facial nerve palsy
      and involvement of maxillary (V2) and mandibular (V3) branches of trigeminal
      nerve along with other nerve palsies. The VIIth nerve palsy in cavernous sinus
      thrombosis has not been reported in the literature.

PMID- 23120421
TI  - Ulcer of the tongue as a presenting feature of pulmonary tuberculosis.
AB  - Oral tuberculosis is very rare and when present they are usually secondary to
      pulmonary tuberculosis. Tuberculous lesions of the tongue have become so
      infrequent that they are virtually a forgotten disease entity and may pose a
      diagnostic problem. The case reported in this paper emphasizes the importance of
      including tuberculosis in the differential diagnosis of any chronic oral ulcer.
      The low number of oral infections by M. tuberculosis could be due to
      underreporting.

PMID- 23120422
TI  - Sinonasal epithelial-Myoepithelial carcinoma-A rare entity.
AB  - Epithelial-myoepithelial carcinoma is a rare salivary gland tumor. It comprises
      less than 1% of all salivary gland tumors. It generally arises from the parotid
      gland. Unusual sites of occurrence include sinonasal tract, lung, trachea,
      lacrimal gland and breast. Histopathologically epithelial-myoepithelial carcinoma
      comprises a dual population of ductal and myoepithelial cells. We report an
      extremely rare case of epithelial-myoepithelial carcinoma occurring in the
      sinonasal tract of young man.

PMID- 23120423
TI  - Solitary oncocytoma of the submandibular salivary gland in an adolescent female:
      A case report.
AB  - We report a rare presentation of Oncocytoma of the submandibular salivary gland
      in an young adolescent female who presented with progressive swelling in the left
      submandibular region since childhood with pain for the past one month. Fine
      needle aspiration revealed Oncocytoma for which a conventional submandibular
      excision was done. There are few articles about the rare presentation of
      submandibular Oncocytoma and literature favors older population for this rarity.
      This case was unique because of its presentation in a young individual and there
      were no supporting published articles available till date.

PMID- 23120424
TI  - Rare case of orbital tumor.
AB  - Most common malignancy involving orbit is secondary deposits. Orbital metastasis
      from thyroid malignancy is rare (3.6%) and is usually from follicular and
      medullary carcinoma thyroid. Here we are presenting the case report of a lady who
      presented with loss of vision and on evaluation was found to have orbital
      metastasis from papillary carcinoma thyroid.

PMID- 23120425
TI  - Angiolipoma of hypopharynx: A diagnostic dilemma.
AB  - Fibro vascular polyps of esophagus are rare tumours. They usually arise close to
      cricopharyngeus muscle. The commonest symptom is dysphagia but regurgitation of
      fleshy mass into mouth, regurgitation of recently digested food and sensation of
      lump in throat are also reported. Several reports of polyp regurgitation and
      subsequent airway obstruction are mentioned. We present a 48-year-old male with
      fibrovascular polyp of hypopharynx. Diagnosis was established by barium swallow
      and oesophagoscopy.Transoral route was used to remove the polyp and
      histopathology reported as angiolipoma.

PMID- 23120426
TI  - Extranodal manifestation of Rosai Dorfman Disease of the nasopharynx.
AB  - The aim of presenting this case is to highlight the fact that extranodal
      manifestation of Rosai Dorfman Disease (RDD) without lymphadenopathy was seen in
      a teenaged girl with recurrent episodes of epistaxis, due to a lobulated mass in
      the nasopharynx, which mimicked malignancy. This case is a rare presentation
      because the extranodal manifestation of RDD in multisystem organs are reported in
      literature, but the nasopharyngeal manifestation without lymphadenopathy is
      unique. The clinical presentation and surgical management of the case by
      endoscopic sinus surgery, the aetiopathology, differential diagnosis and review
      of literature are described here.

PMID- 23120427
TI  - Granular cell tumour vocal cord in an adolescent child-A case report.
AB  - Granular cell tumors are benign relatively rare lesions that can occur in any
      organ in the body. Tongue is the most predilected site. Granular cell tumor vocal
      cord is even rarer and typically occurs in the third decade of life. It generally
      presents as a single lesion, but multiple lesions can also occur. Patients
      present with hoarseness andor airway obstruction. Granular cell tumors are
      resistant to radiotherapy, and therefore surgical excision is the treatment of
      choice. We report the case of granular cell tumor vocal cord in a 13-year-old
      male child in whom direct laryngoscopic excision of the tumor was advocated.

PMID- 23120428
TI  - Rosai Dorfman syndrome - A rare clinical entity.
AB  - Sinus histiocytosis with massive lymphadenopathy (also known as Rosai Dorfman
      syndrome) is a unique disease of unknown etiology with a childhood predilection.
      It is an uncommon benign condition, often confused with lymphoma. Patients
      usually present with massive, painless, bilateral cervical lymphadenopathy and
      clinical course is variable. This condition has been sporadically reported in
      Indian literature. Here we report a 26-year-old women presenting with a painless
      bilateral cervical lymphadenopathy. A FNAC from cervical lymph node was
      compatible with Rosai Dorfman syndrome and confirmed histopathologically.

PMID- 23120429
TI  - Aesthetics in ear surgery: A comparative study of different post auricular
      incisions and their cosmetic relevance.
AB  - Post auricular incisions play a very important role in the final post operative
      position of pinna and hence keeps a cosmetic bearing. This study shows that
      "behind the groove" incision gives a better post operative result in terms of
      minimal deviation of pinna and thus is cosmetically a better incision. This study
      also includes a new method to measure the conchomastoid or the post auricular
      angle.

PMID- 23120430
TI  - ORL-HNS training in South Africa.
AB  - An out line of the scheme of training specialists in Otorhinolaryngology-Head and
      Neck Surgery (ORL-HNS) in South Africa is given and the difference with Indian
      training discussed.

PMID- 23120431
TI  - Malignant myoepithelioma of the mastoid region - A case report.
AB  - A 23-year-old male patient presented with a post auricular mass and an attico
      antral type of chronic suppurative otitis media. He underwent excision of the
      mass and canal wall down mastoidectomy. Histopathological diagnosis of malignant
      myoepithelioma was made.The patient refused treatment and later he died with
      systemic metastasis.This case is reported for the rarity of the site, young age
      of presentation and aggressive behaviour.

PMID- 23120432
TI  - Nasal teeth: A case report.
AB  - The ectopic eruption of the teeth into the nasal cavity is a rare phenomenon. We
      report a case of nasal tooth in the left nasal cavity in a 64-year-male. We
      describe the clinical and radiological findings of the case and discuss their
      etiology, diagnosis, complications and treatment.

PMID- 23120433
TI  - Atticoantral disease - revisited.
AB  - Atticoantral disease is very common in this part of the world. The clinical
      presentation and the otomicroscopic examination of the ear may just reveal the
      tip of the iceberg as to the extent of disease. Often we have found that minimal
      disease with good hearing have extensive mastoid involvement.

PMID- 23120434
TI  - Transfacial nasal approach to paranasal sinuses, nasopharynx and anterior skull
      base.
AB  - There are different surgical approaches to remove lesion involving the large
      central lesions of nasal cavity, sinus and nasopharynx with anterior skull base
      and retromaxillary extension depending on the site extent and the type of tumor.
      In this paper, we are describing a method that is rhinological and is a direct
      approach for removal of such lesions in 6 patients.

PMID- 23120435
TI  - Foreign body in tracheobronchial tree.
AB  - Inhalation of foreign body into the tracheobronchial tree is a medical emergency
      sometimes resulting into sudden death. The current mortality rate due to foreign
      body inhalation ranges from 0% to 1.8%. Children with or without positive history
      of aspiration were examined and diagnosis was made on the basis of history,
      clinical findings, radiological evaluation and strong index of suspicion. A
      review of 30 cases of suspected foreign body aspiration revealed, children
      between 6 months were found to be very vulnerable to aspiration. Majority of
      children were boys. 80% of the patients had positive history of inhalation. Only
      50% of the patients presented immediately i.e. within 24 hours after aspiration.
      Common symptoms were cough and respiratory distress. Decreased air entry was the
      significant clinical sign (50%). Obstructive emphysema and mediastinal shift were
      found in the majority of cases (50%). Rigid bronchoscopy under general
      anaesthesia and patient ventilating using a jet ventilator is a very safe and
      effective technique.

PMID- 23120436
TI  - Lateral rhinotomy - revisited.
AB  - The lateral rhinotomy approach is one of the most commonly used techniques for
      exploration of the difficult sinonasal masses. Though endoscopic advances have
      progressed rapidly since last few years, but the excellent exposure provided by
      the lateral rhinotomy approach makes it suitable for resection of sinonasal
      masses with extensive spread. Our study is an attempt to establish the different
      spectra of pathologies encountered in the sinonasal region, which were removed by
      the lateral rhinotomy approach and to establish its importance in the context of
      modern rhinological surgeries.

PMID- 23120437
TI  - Penetrating neck injuries.
AB  - The incidence of penetrating and lacerated neck injuries has been rising in
      recent decades largely because of urban violence. Injury to the neck frequently
      results in multiple regional injuries and in addition poses serious threat to
      vital structures in the neck.From 1999 to 2005, forty-two cases of penetrating
      neck injuries which were treated in our hospital were included in this study.
      Thirty one (73.8%) injuries were due to homicide, six cases (14.2%) were due to
      suicide attempt and five (11.9%) were accidental injuries. Surgical management
      included tracheostomy neck exploration and wound repair. All the patients were
      followed up for a minimum period of six months. Six patients (14.2%) had
      unilateral vocal cord paralysis. Two patients (4.7%) developed tracheal
      stenosis.A proper evaluation, rapid air way intervention and proper surgical
      repair are essential for a successful outcome.

PMID- 23120438
TI  - Prospective study of 100 cases of underlay tympanoplasty with superiorly based
      circumferential flap for subtotal perforations.
AB  - OBJECTIVE: Underlay Tympanoplasty with superiorly based circumferential flap for
      dry subtotal perforations. STUDY DESIGN: A prospective study of cases with dry
      subtotal perforations, which underwent surgery between August 2001-Feb. 2004.
      SETTING: Study was conducted on patients attending ENT OPD in S.M.S. Medical
      College and Hospital from August 2001-Feb. 2004 with dry subtotal perforations.
      RESULTS: It was noted that 89% of the cases were in the age group of 11 to 40
      years, while one case was of 7 years of age and 9% of cases were between the age
      of 41-50. 50% of the cases had dry ear for less than 3 months while 75% of cases
      had dry ear for less than 1 year. Graft take rate was 97% with completely healed
      tympanic membrane. Rejection of the graft was observed in 2% of the cases.
      Hearing gain of 10-30dB was achieved in 95% of the cases. 7% of the cases
      suffered minor complications like otitis media with effusion (2%) retraction (2%)
      and lateralization (1%). CONCLUSION: Duration for which ear has been dry did not
      affect the results. 49% of cases had dry ear for less than 3 months, with good
      graft take up rate and hearing gain. Pneumatization of mastoids, had a direct
      relationship with, post operative hearing gain, which ranged from 10-30 dB, in
      95% of the cases. We observed, 97% graft take rate. Rejection of the graft was
      found in only 2% of the cases. 97% of the graft take rate and good hearing gain
      in our study can be correlated with expertise technique to deal with subtotal
      perforations.

PMID- 23120439
TI  - Management of the node negative early carcinoma tongue.
AB  - OBJECTIVE: To determine the role of thickness of the primary lesion in early
      Squamous Cell Carcinoma (SCC) of the oral tongue for decision-making regarding
      the management of possible occult cervical node metastases. SETTING: Tertiary
      referral centre PATIENTS: Patients who were treated by the authors for early (T1,
      T2) primary lesions in the oral tongue in two malignancy treatment centres of the
      Armed Forces Medical Services were included in this prospective study. Where the
      primary lesion was less than 04 mm in depth, the neck was not addressed
      electively. Those who developed nodal disease in the neck on follow up were
      subjected to comprehensive neck dissection. In those patients where the tumour
      thickness was more than 04 mm, the neck was addressed with at least a supra
      omohyoid neck dissection. Postoperative radiotherapy was given as per standard
      indications. The patients were followed up as per standard protocol. RESULTS:
      Disease free survival rate achieved was 86% and this compares well with survival
      rates achieved by other workers. CONCLUSION: Treatment of neck nodes in early
      (T1,T2) SCC of the oral tongue can be expectant in cases where tumour thickness
      is less than 04 mm, but where it is more than 04 mm elective treatment of the
      neck is recommended.

PMID- 23120440
TI  - Peritonsillar abscess - Do we need anaerobic cover?
AB  - OBJECTIVE: To find out the usability and advantage with regard to the advent of
      new and more costly antibiotics. In the treatment of Peritonsillar abscess the
      demonstration of, both aerobic and anaerobic organisms has raised the question of
      possible need to treat with antibiotics effective against anaerobes. It was in
      this very context that this study was planned to find out if we still have an
      economically and easily available antibiotic to treat Peritonsillar abscess.
      CONCLUSIONS: Injectable penicillin is the drug of choice in PTA as GABHS and
      staphylococcus aureus coagulase positive are the most common organism associated
      with this condition. Even where penicillin resistant organism is present,
      effective management of the abscess is possible if it is drained well and weak
      hydrogen peroxide gargles are used along with injectable penicillin.

PMID- 23120441
TI  - Human otoacariasis.
AB  - Accidental entry of foreign bodies into the ear canal is very common. Animate
      foreign bodies constitute upto 14% of cases, majority being the cockroaches. Not
      many cases of ticks entering into human ears are found in the scientific
      literature. Even the available reports are from South Africa, Nepal, Malaysia,
      Chile and Srilanka. This Indian study discusses the occurence, clinical features,
      the methods adopted in the removal and the complications of tick infestation of
      human ear. A total of 144 cases of ticks entering the human ears were studied
      over a period of two years from Jan 2004 to Dec 2005. This report represents one
      of the largest recorded series of human otoacariasis available in the Indian
      literature.

PMID- 23120442
TI  - The study of co-morbid conditions in children with allergic rhinitis, from
      Mumbai, Maharashtra, India.
AB  - Allergic rhinitis (AR), an allergen-induced inflammation of the nasal mucosa, is
      frequently associated with co-morbid conditions. It is important to recognize the
      onset and existence of these co-morbid conditions, for adequate treatment and
      prevention of the development of new allergen sensitizations and air-way
      hypersensitivities. The aim of our study was to determine the prevalence of co
      morbid conditions associated with AR, in Indian children. We selected 65
      consecutive children below the age of 18 years, who attended the Allergy and
      Asthma Clinic of our hospital, between March 1, 2005 to November 30, 2006 and
      compared them with the available literature. The most common co-morbid condition
      with AR was asthma (75.4%), followed by urticaria (33.9%), conjunctivitis (29.2%)
      and sinusitis (23.1%) in that order. Two patients (3.1%) each, had adenoid
      hypertrophy and nasal polyps. Psoriasis was seen in 4/65 (6.2%). Four patients
      (6.2%) were free from any co-morbid conditions as opposed to 61/65 (93.8%), who
      suffered from one to three co-morbid conditions each. Co-morbid conditions are a
      rule rather than an exception, the most common association being asthma. Asthma
      often is asymptomatic and routine PFT testing is valuable. The association of
      psoriasis is interesting.

PMID- 23120444
TI  - Unusual presentation of laryngeal foreign bodies - report of two rare cases.
AB  - Aspiration of a foreign body into the respiratory tract is a common and serious
      problem in childhood but is rare in adults. Two interesting cases in which the
      diagnosis of foreign body in the larynx was not suspected preoperatively are
      being reported. A three and half year old female child was diagnosed as a case of
      bronchitis and was later found to have a metallic spring in the supraglottic
      region which was removed by direct laryngoscopy under general anesthesia. The
      other patient, a 32-year-old male, was diagnosed to have a fibrous lesion in the
      larynx one year previously, and on laryngoscopy a vegetable, spiculated foreign
      body was found after excising the fibrous lesion on the left false cord. Both the
      cases are symptom free 18 months after endoscopy.

PMID- 23120443
TI  - Head and Neck Squamous Cell Cancer: Biology (II) and Translational Methods.
AB  - The essential steps implicated in carcinogenesis are acquisition of autonomous
      proliferative signaling; inhibition of growth inhibitory signals; evasion of
      apoptosis; immortalization; angiogenesis; tissue invasion and metastasis. A
      considerable progress in understanding the process of carcinogenesis has further
      stimulated the high throughput translational methods and systems biology approach
      to revolutionize this field of cancer biology. The era of molecular targeted
      therapy has dawned and would soon replace the more 'toxic' classical 'broad
      spectrum' cancer chemotherapy. This review summarises the steps of carcinogenesis
      and the concepts involved in translational methods, systems-biology and molecular
      targeted therapy.

PMID- 23120445
TI  - Synovial sarcoma of parapharyngeal and retropharyngeal space: A case report.
AB  - Synovial sarcoma is a rare tumour of head and neck. It was first described by
      Pack and Ariel in 1950. Synovial sarcoma is said to be the commonest sarcoma of
      hands and feet and they are usually found adjacent to the articular surfaces.
      They rarely occur in extra-articular sites originating from bursa or tendon
      sheaths. Parapharyngeal space appears to be the site of predilection in most of
      the cases occurring in the head and neck region. One such case is being reported
      here along with its management and review of literature.

PMID- 23120446
TI  - Anticoagulant therapy induced haematoma presenting as acute dysphagia.
AB  - Oropharyngeal haematoma secondary to bleeding from anticoagulant therapy is
      uncommon and difficult to manage. We report a case of Oropharyngeal haematoma
      secondary to anticoagulant Acitrom (Nicoumalone) which was treated successfully
      with Inj Vit K.

PMID- 23120447
TI  - Secondary pharyngeal tuberculosis.
AB  - Secondary tuberculosis of pharynx is a rare condition as pharynx is not a common
      site for clinically manifest tuberculosis. A rare and unusual case of secondary
      oropharyngeal tuberculosis in a 40 years male patient, who presented with an
      ulceroproliferative lesion of oropharynx extending to nasopharynx and
      laryngopharynx is being reported.

PMID- 23120448
TI  - Paranasal mucormycosis: Unusual presentation in otherwise healthy child.
AB  - Mucormycosis is the fungal infection usually involving immunocompromized
      individuals. In this article we present a case of mucomycosis affecting a 12-year
      old healthy boy who was treated by endoscopic surgical technique. Postoperatively
      patient was put on Amphotericin B nasal douching and oral Itraconazole. There was
      no recurrence till the last follow up at six month postoperatively.

PMID- 23120449
TI  - Inflammatory pseudotumours of the paranasal sinuses.
AB  - Inflammatory pseudotumors are clinocopathologically distinctive but biologically
      controversial entities. They have been described in the lungs, abdomen,
      retroperitoneum and extremities, but rarely affect the head and neck region. This
      report is of 2 cases of pseudo tumor of the paranasal sinuses with varied
      clinical presentation and successful outcome following treatment.

PMID- 23120450
TI  - Second branchial cleft cyst causing internal jugular vein thrombosis - A case
      report.
AB  - The branchial cleft cyst also known as lateral cervical cyst is usually present
      in the lateral part of neck deep to sternocleidomastoid muscle at the junction of
      its upper third and lower two thirds. Branchial cysts are known for repeated
      infection with sudden increase in size and pain and for its recurrence.
      Thrombosis of major vessels of neck secondary to recurrent infection and
      inflammation of branchial cyst is extremely rare. Here we present the first case
      of internal jugular vein thrombosis; a rare complication seen with branchial cyst
      in a 54-year-old male. The patient was treated initially with antibiotics
      followed by excision of cyst and ligation of internal jugular vein without any
      complication.

PMID- 23120451
TI  - Primary extraskeletal Ewing's sarcoma of the maxilla with intraorbital extension.
AB  - Extraskeletal Ewing's sarcoma is often described as a tumour involving the soft
      tissues of the lower extremities and the paravertebral region. Primary Ewing's
      sarcoma of the cranium is extremely rare, with only 17 cases reported so far
      [24]. Involvement of the paranasal sinus is a very rare entity. Involvement of
      facial bones is characterized by clinical and radiological features distinct from
      those commonly observed in other sites. Because of the above peculiarities a
      delay in diagnosis and thus in starting treatment is very probable in such cases.
      Primary Ewings sarcoma rarely arises in the facial skeleton and only occasionally
      in the maxilla. To date, there have been 22 cases of maxillary Ewing's sarcoma
      reported in the English-language literature [25]. We report here a new case of
      Ewing's sarcoma localized to the maxillary sinus, nose and the orbit,
      successfully treated by surgery, local high dosage radiotherapy and systemic
      chemotherapy.

PMID- 23120452
TI  - Anterior pneumatization of the maxillary sinus - Presenting as a facial swelling.
AB  - Over pneumatization of the paranasal sinuses is a fairly common finding on
      computerized tomography; but involvement of a small segment of the maxillary
      sinus especially the anteromedial aspect is very rare. We report a case of a
      twenty year old male who presented with a facial swelling. On CT scan, the
      swelling was found to be due to pneumatization of the anterior part of the
      maxillary sinus. Surgical treatment was carried out for cosmetic reasons.

PMID- 23120453
TI  - Cochlear implantation in branchio-oto-renal syndrome - A surgical challenge.
AB  - Branchio-oto-renal syndrome (Melnick-Fraser Syndrome) is a rare Autosomal
      Dominant disorder characterized by the syndromic association of branchial cysts
      or fistulae along with external, middle & inner malformations and renal
      anomalies. Incomplete penetrance and variable expressivity are common with the
      phenotypic variation ranging from mild to severe forms & consisting of various
      eye, ear, oral and craniofacial abnormalities. Mutations in the EYA1 gene on
      chromosomal site 8q13.3 are identified as the primary cause of BOR syndrome. We
      present a 3year old child with BOR syndrome, who came to us with bilateral low
      set, malformed ears & profound cochlear hearing loss along with bilateral
      branchial fistulae & unilateral renal agenesis. This child underwent successful
      cochlear implantation recently. The clinical presentation, pre-operative
      investigations, intra-operative findings & post-op habilitation status are
      presented with special highlights on the unique facial nerve course along with
      middle and inner ear anomalies which posed a surgical challenge during cochlear
      implantation.

PMID- 23120454
TI  - Frontal sinus osteomyelitis with midline fistula.
AB  - Chronic osteomyelitis of frontal sinus is a rare complication of recurrent
      sinusitis. The pent-up secretions in the sinus may result in pressure necrosis of
      the containing wall of frontal sinus resulting in persistently discharging
      fistula. Here we present a case of chronic osteomyelitis of frontal sinus with
      persistent midline fistula over forehead in a 30 year old male managed surgically
      by osteoplastic flap procedure and frontal sinus obliteration with abdominal fat.

PMID- 23120455
TI  - Cervical neuroblastoma.
AB  - Cervical neuroblastoma is relatively uncommon. It present, most often as a firm
      mass in the lateral neck. Primary neuroblastomas of the neck usually arise in the
      cervical sympathetic ganglia. They are the sixth most common head and neck
      extracranial neoplasms. Neuroblastoma is the most common malignancy in children
      under 1 year of age. No known cause of Neuroblastoma has been reported.

PMID- 23120456
TI  - Autologous embedded foreign body of mobile tongue.
AB  - Foreign bodies of upper aerodigestive tract are common otorhinolarygological
      emergencies. The foreign bodies of mobile tongue are however very rare and there
      are only limited case reports in literature. The case of a young female with an
      autologous foreign body mobile tongue with unusual presentation is presented.

PMID- 23120457
TI  - Huge pleomorphic adenoma of nasal cavity.
AB  - Pleomorphic adenoma is a common benign tumour of the salivary gland that has
      elements of both epithelial and mesenchymal tissue. It is commonly seen in major
      salivary glands, parotid being the most common site followed by submandibular
      gland. However it can sometimes arise from minor salivary glands that are
      distributed throughout the upper aerodigestive tract and paranasal sinuses. We
      report a case of a 45 yrs. Old male patient, who presented with progressive nasal
      blockage and intermittent minor episodes of epistaxis from left nostril for 1 1/2
      years. Lateral Rhinotomy revealed a well encapsulated lesion attached to the
      nasal septum, which was excised completely. Histopathology revealed it to be
      Pleomorphic Adenoma without any features of malignancy. Lesion is a rare one
      hence reported.

PMID- 23120458
TI  - Dermatofibrosarcoma protuberans: Rare cause of head and neck swelling.
AB  - Dermatofibrosarcoma protuberance of head and neck is a rare neoplasm and accounts
      for less than one percent of Head and Neck Neoplasm. The objective of this report
      is to understand etiology, presentation, histopathologic identification and
      treatment option for this tumour. The goal of current report is to acquaint the
      clinician with presentation and treatment option for this disease.

PMID- 23120459
TI  - Bilateral recurrent laryngeal nerve palsy following blunt neck trauma.
AB  - Blunt trauma neck to larynx is an uncommon injury that results in a wide spectrum
      of damage to endolaryngeal soft tissues as well as underlying cartilaginous
      skeleton leading to upper airway obstruction requiring emergency tracheostomy. A
      case report of blunt trauma neck anterior is presented who developed upper airway
      obstruction necessitating tracheostomy. Indirect Laryngoscopy and fibre optic
      examination identified vocal cord paralysis as primary cause of upper airway
      obstruction although X ray soft tissue neck and CT neck revealed fracture hyoid
      as well as hematoma surrounding the laryngeal frame work. Emergency tracheostomy
      was done and patient recovered uneventfully.

PMID- 23120460
TI  - Evaluation of bismuth subgallate and adrenaline paste as haemostat in
      tonsillectomy bleeding.
AB  - Haemorrhage is a frequent and often feared complication of tonsillectomy. This
      has prompted the use of a variety of topical haemostatics such as bismuth
      subgallate to achieve haemostasis and reduce the risk of postoperative
      haemorrhage. In this study effect of bismuth subgallate and adrenaline paste was
      investigated. A total of twenty five subjects undergoing tonsillectomy were
      randomly recruited. The distinctive feature of study was that each patient
      constituted a matched pair, with left tonsillar fossa acting as control and right
      tonsillar fossa as trial side. Bismuth subgallate adrenaline paste was made by
      mixing 13 gm of Bismuth subgallate powder with 10 ml of normal saline and 0.35 ml
      of 1: 1000 adrenaline. The application of twin reagent paste resulted in reduced
      blood loss in trial fosse (60.8 +/- 19.3 ml) as compared to control fossa (91.2
      +/- 20.27) (p < 0.0001). Similarly the average number of ligatures applied to
      control bleeding was also less in trial fosse. Only one patient reported
      reactionary haemorrhage while there was no report of secondary haemorrhage from
      amongst tonsillar fosse on trial side. However, two patients presented with
      secondary haemorrhage from control side fosse.

PMID- 23120461
TI  - Hydrogen peroxide as 'defogger' in indirect laryngoscopy.
AB  - Indirect laryngoscopy examination is a routine clinical procedure for visualizing
      larynx and hypopharynx. Many methods are described in literature to prevent
      fogging over the mirror during the examination. Authors have used hydrogen
      peroxide 0.75% w/v solution as a defogging agent during indirect laryngoscopy
      examination and found it safe and cost effective.

PMID- 23120462
TI  - Betropharyngeal abscesses: Revisited.
AB  - Retropharyngeal abscesses were fairly common in preantibiotic era but the advent
      of antibiotics has reduced the overall incidence of these abscesses. They still
      continue to occur specially in developing world and carry significant morbidity
      and even mortality if not managed properly. The prevalence of this abscess in the
      young children pose a bigger challenge, as the examination of oral cavity is
      difficult. Emphasis is placed on the age, sex, type, and duration of symptoms,
      bacteriology, methodology of diagnosis, therapy and complications. With proper
      antibiotic cover and surgical management, majority of patients today survive
      without major residual squeal. Hereby we present a series of 15 cases of
      retropharyngeal abscess.

PMID- 23120463
TI  - Retrospective study of descending cervical mediastinitis.
AB  - OBJECTIVE: Descending cervical mediastinitis can occur as a complication of
      oropharyhgeal and cervical space that spread to the mediastinum vis cervical
      space. Descending mediastinitis represent a virulent form of mediastinal
      infection requiring prompt diagnosis and treatment to reduce high morality
      associated with the disease. Surgical management and a particularly optimal form
      of mediastinal drainage remain controversial. METHOD: From 1998-2004, eighteen
      patients were treated in our institution. Surgical treatment consisted more than
      2 times. Cervical drainage associated with drainage of the mediastinum through a
      thoracic approach in 11 patients with pleural drainage in 8 patients. RESULT: The
      outcome was favorable in eleven patients who had mediastinum drained through
      thoracotomy. One patient who was not drained died with tracheo-oesophageal
      fistula. Main culprit neck space is pre and para tracheal space which lead to
      anterior, superior and posterior mediastinal collection in our series. The
      tracheostomy is of immense help not only in opening cervical space collections
      and also to secure a partially compromised airway.

PMID- 23120464
TI  - Cytogenetics in head and neck cancer.
AB  - Cytogenetics or the study of chromosomes has been an important tool in oncology.
      It localizes the abnormality on a particular chromosome segment as such but, the
      molecular analysis on the other hand focuses the exact gene of interest. Hence
      both are complimentary. Classical cytogenetics in combination with recent
      molecular techniques has given rise to various molecular cytogenetic analytical
      techniques such as florescent in-situ hybridization (FISH), spectral karyotyping
      (SKY) and comparative genomic hybridization (CGH). The role of telomeres and its
      concerned enzyme telomerase is important in carcinogenesis. This article
      summarizes the various cytogenetic techniques and presents an overall view of the
      importance of cytogenetcs in head and neck cancer.

PMID- 23120465
TI  - Sarcomas of head and neck - A 10 yrs experience.
AB  - 38 cases of sarcoma of head and neck region were analysed in a retrospective way
      in relation to age, anatomic location, histological, clinical profile, and
      surgical approaches. Compared to other types of head and neck neoplasms, such as
      squamous cell carcinoma, soft tissue sarcomas have low rates of regional
      metastases. However the biological behaviour of soft tissue sarcoma is more
      aggressive specially in paediatric age group. In the present series, CT scan was
      considered as the primary modality of investigation. Surgery generally has been
      recommended as the primary method of treatment for achieving local control,
      except in those high-grade tumours arising in sites not amenable to resection. 3
      year and 5-year survival rates in this present series 50% and 31.6% respectively.

PMID- 23120466
TI  - Clinicopathological and radiological evaluation of cervical lymph node metastasis
      in head and neck malignancies.
AB  - The cervical lymphadenopathy due to metastasis carry poor prognosis. The status
      of cervical nodes is of critical interest to surgical, radiation and medical
      oncologists who manage patients with head and neck cancers. We conducted a
      prospective randomized study to assess the role of palpation, ultrasound and CT
      in detection of cervical metastasis in 25 patients presented to us with head and
      neck malignancy irrespective of cervical nodal status. It was observed that
      clinical examination was least sensitive (73.33%) when compared with computerized
      tomography (80%) and ultrasound (93.93%). The computerized tomography was found
      to be most specific (90%) when compared to clinical examination or
      ultrasonography (70% each).

PMID- 23120467
TI  - Ultrasonography: Its role in nodular thyroid disease.
AB  - OBJECTIVE: The objective was to correlate the number, size and extent of the
      nodules as determined during the preoperative clinical examination of the thyroid
      gland, USG, intra-operative examination and histopathology. Also, FNAC (with or
      without USG guidance) and USG findings suggestive of malignancy were correlated
      with the final histopathology. SETTING: Tertiary referral centre PATIENTS: A
      retrospective chart review was done for 106 patients who underwent surgery for
      benign or malignant nodular thyroid disease in our center, between Jan 2004-Dec
      2006. RESULTS: USG has 7 times higher predictive value than clinical examination
      in detecting number of nodules and determining size of nodules. USG guided FNAC
      has a sensitivity of 85.71% and specificity of 90.0% in detecting malignancy in
      nodular thyroid disease. However for predicting malignancy in thryoid nodules,
      this study shows that USG has a sensitivity of 20.0% and specificity of 97.67%.
      CONCLUSION: In patients with nodular thyroid disease, USG can accurately
      determine the number and the size of the nodules. It is extremely useful in
      guiding FNAC; However its role in predicting malignancy is doubtful. We therefore
      recommend that USG guided FNAC be carried out as a routine in the evaluation of
      thyroid nodules.

PMID- 23120468
TI  - Outcome analysis of benign vocal cord lesions by videostroboscopy, acoustic
      analysis and voice handicap index.
AB  - Benign vocal cord lesions affect vibratory vocal fold function resulting in
      significant dysphonia. A prospective study of 30 patients with benign vocal fold
      lesions was undertaken at our centre to compare the pre and post operative voice
      using videostroboscopy, voice analysis and voice handicap index. The vibratory
      pattern of the cord improved as evidenced by the stroboscopic parameters
      symmetry, mucosal wave and glottic closure (p<0.05). Voice analysis showed a
      trend towards normalcy but the values obtained did not attain statistical
      significance. Voice handicap index showed a reduction in the total and the
      subscales scores. Videostroboscopy along with acoustic analysis and voice
      handicap index are useful tools in the objective and subjective assessment of the
      effectiveness of treatment in patients with benign vocal cord lesions. Their
      routine use in a voice clinic is recommended.

PMID- 23120470
TI  - Reparative granuloma following stapes surgery.
AB  - Reparative granuloma of the oval window is an uncommon complication of stapes
      surgery, which usually develops within one to six weeks after operation and
      causes a sudden hearing loss and disturbance of balance. We report 2 cases of
      post-stapedectomy reparative granuloma that developed during the tenure of senior
      surgeon (AM).

PMID- 23120469
TI  - Adult tonsillectomy and day care surgery.
AB  - OBJECTIVE: To evaluate the safety of adult tonsillectomy as a day care surgery
      METHODS: Records of 664 patients above the age of 12 years, who underwent
      tonsillectomy were analysed. These patients were operated in our department
      within January 1999 and September 2002. Only 13 patients (1.95%) had post
      operative bleeding and were readmitted after discharge. The data of these
      patients were collected from medical records as well from the morbidity meeting
      proceedings and was reviewed retrospectively. Statistical analysis was done by
      using 'one sample t-test'. RESULTS: Overall incidence of post operative bleeding
      was 1.95%. None of our pateients bled with 12 hours of Surgery, 0.3% had bleeding
      between 12 to 24 hours after tonsillectomy and 1.65% encountered bleeding between
      24 hours to the 6th post operative day. Bleeding was not major in majority of
      patients as only 0.45% of the patients required second anesthesia to control the
      bleeding and only 0.35% of patients required blood transfusion to replace the
      lost blood volume. In addition, higher incidence of bleeding was seen in males,
      in the older age group of 31-40 years, patients with obstructive sleep aponea and
      in patients where tonsillectomy was done by electrocautry dissection. CONCLUSION:
      Based on these observations, we conclude that Adult tonsillectomy can be safely
      preformed in our setup.

PMID- 23120471
TI  - An unusual complication of CSOM - Lateral sinus thrombosis with lung abscess: A
      clinicoradiological study.
AB  - AIMS: To present a case report of a child presenting with lateral sinus
      thrombosis with bilateral multiple lung abscesses as a rare consequence of CSOM
      with an emphasis on the radiological findings. MATERIAL AND METHODS: An 11-year
      old male child with a history of pyrexia of unknown origin, right-sided
      torticollis, cough with expectoration and right ear discharge was referred to us
      from department of paediatric medicine. Chest examination revealed dull areas on
      percussion and areas with bronchial breath sounds on auscultation bilaterally.
      Otological examination revealed right attic retraction pocket filled with
      cholesteatoma, post-auricular tenderness and Greisinger's sign along with foul
      smelling muco-purulent discharge. RESULTS: Routine blood investigations revealed
      normocytic normochromic anaemia, polymorpho-nuclear leucocytosis and raised ESR.
      Audiological investigations showed a right-sided mixed hearing loss. Digital
      radiography of chest showed multiple thin walled cavities involving all of the
      lung zones bilaterally. USG (Ultrasonography) of neck showed thrombosis of right
      internal jugular vein. CT scanning of head, neck and thorax showed soft tissue
      collection within the right mastoid with erosion of posterior wall & presence of
      gas bubble in the right sigmoid sinus and thrombosis of right internal jugular
      vein and multiple abscess cavities occupying both lung parenchyma. The patient
      was initially managed with conservative antibiotic therapy for lung abscess
      followed by radical mastoidectomy and thromboembolectomy from the lateral sinus.
      CONCLUSION: Otogenic lung abscess though rare in this present postantibiotic era,
      it can occur in underprivileged and poor population like our country.

PMID- 23120472
TI  - Lacrimal sac diverticulum due to Rhinosporidiosis.
AB  - Rhinosporidiosis is a disease affecting primarily the mucosa of nose, conjunctiva
      and urethra. Larynx, trachea, skin and lungs are less frequently involved. It is
      endemic in some Asiatic regions, affecting people of any age and sex. Its
      manifestation is a polypoid mass growing inside the affected nasal cavity and the
      treatment is surgical excision, with adjuvant radiotherapy and chemotherapy.
      Rhinosporidium seeberi is the aetiological agent. The lesion may recur and
      sometimes cause osteolytic bone lesions. A case of Rhinosporidiosis with an
      unusual feature of spread to the nasopharyngeal area and chronicity of 2 years is
      presented.

PMID- 23120473
TI  - Primary exophytic laryngeal amyloidosis presenting as sudden airway obstruction.
AB  - Primary amyloidosis of larynx is an uncommon phenomenon, the precise
      etiopathogenesis of which is not yet clear. It can present with slowly increasing
      hoarseness or difficulty in breathing. It presents more commonly as infiltrative
      lesion, exophytic presentation is a rare occurrence.

PMID- 23120474
TI  - Retropharyngeal lipoma - a case report.
AB  - Lipomas of the retropharyngeal region are rare. They attain a large size before
      producing symptoms like dyspnoea and dysphagia. A case of lipoma in the
      retropharyngeal space is reported with characteristic radiological findings and
      surgical management.

PMID- 23120475
TI  - Frontoethmoidal mucocele with orbital and intracranial extension.
AB  - We report a case of a giant frontoethmoidal mucocele extending to the orbit and
      anterior cranial fossa. Clinically, the patient had an insidious onset of
      clinical presentation with no intracranial symptoms. We present its CT, MRI and
      histpathological features with a brief review of literature. Various surgical
      approaches are also discussed.

PMID- 23120476
TI  - Thyroglossal duct cyst in hyoid bone: Unusual location.
AB  - A 10-year-old female presenting with a discharging sinus in the midline of the
      neck of one month duration was diagnosed to have a thyroglossal sinus. She
      underwent sistrunk's operation, intra-operatively a thyroglossal duct cyst was
      atypically sited in the intrahyoid region. The cyst may be located in the
      intralingual, suprahyoid, thyrohyoid or suprasternal region. A literature search
      revealed that this intrahyoid location of a thyroglossal duct cyst is extremely
      rare and so far only three cases have been reported. A case and review of
      literature regarding this unusual entity are presented.

PMID- 23120477
TI  - Bilateral aggressive inverted papillomas: A changing scenario.
AB  - OBJECTIVES: The ideal management of bilateral, recurrent inverted papillomas is
      intriguing and often controversial. We describe the ideal management of such
      tumors. DESIGN: Retrospective, case series METHODS: The three patients in this
      series inspite of several surgical procedures in the past had recurrences and
      behaved in an aggressive fashion. The patients underwent surgical excision by
      either bilateral lateral rhinotomy, midfacial degloving or craniofacial
      approaches. RESULTS: One patient who underwent excision by midfacial degloving
      approach had recurrence. This was removed by lateral rhinotomy approach. Two
      patients were subjected to radiotherapy due to the presence of mitotic figures on
      histopathology. All the patients are asymptomatic at 6 months follow-up.
      CONCLUSION: Aggressive inverted papillomas may have varied presentation. They
      could have multiple recurrences, bilateral presentation or intracranial
      extension. They can be effectively managed with bilateral lateral rhinotomy or
      cranio-facial resection. Adjuvant radiotherapy has a role in controlling
      recurrences.

PMID- 23120478
TI  - Leiomyosarcoma of larynx: A case report.
AB  - Leiomyosarcoma of larynx is a rare tumor. We report a case of 70 year old male
      who had presented to our department with respiratory distress and stridor.
      Patient's emergency was managed with tracheostomy with subsequent total
      laryngectomy and post-op external radiotherapy. One year into follow-up, patient
      is tumor free.

PMID- 23120479
TI  - Papillary carcinoma of thyroglossal cyst.
AB  - Malignancy of thyroglossal cyst is a rare entity. Medical literature has reported
      only a very few cases till date. Histopathologically papillary carcinoma of
      thyroglossal cyst is the most common variety encountered in clinical practice.
      Surgical excision by Sistrunk operation is the standard treatment of choice
      followed by subtotal or total thyroidectomy whenever indicated. We report here
      two cases of thyroglossal cyst carcinomas and their respective management.

PMID- 23120480
TI  - Cystic papillary carcinoma of thyroid gland - A rare case.
AB  - A case of cystic papillary carcinoma of thyroid gland is reported, which depicts
      typical ultrasonographic features that help in diagnosing a rare case with
      diagnostic certainty.

PMID- 23120481
TI  - Removal of a metallic foreign body in the neck with a magnet: A case report.
AB  - A 26-year-old man, presented to our department with history of a metallic foreign
      body in the neck. On wound exploration under local anaesthesia, the foreign body
      was not readily palpable. It was removed with the help of a magnet.

PMID- 23120482
TI  - Unusual foreign body in throat.
AB  - Live fish in throat is a rare foreign body. Here we present two such cases. The
      foreign body were removed under general anaesthesia and nutrition was maintained
      by Nasogastric tube for few days. Patient returned to normal duty within a week.

PMID- 23120483
TI  - Preauricular malignant lymphoma masqurading as benign pleomorphic adenoma - A
      rare tricky presentation.
AB  - Lymphoma in the head neck area most commonly present as cervical lymph node
      swelling followed by tonsillar enlargement but the presentation as sole
      preauricular swelling without systemic involvement is a very rare finding. Here
      we present a case of malignant lymphoma Grade I, presenting as a single
      prauricular swelling masquerading as a benign pleomorphic adenoma, in a 24 year
      old girl.

PMID- 23120484
TI  - Lupus vulgaris of pinna.

PMID- 23120485
TI  - Alveolar soft part sarcoma of tongue base - A rare presentation of a rare tumor.
AB  - Alveolar soft part sarcoma is a rare, aggressive malignancy of uncertain
      histologic origin and enigmatic clinical behaviour. It has a characteristic
      histopathological picture, with a propensity for vascular invasion and distant
      metastasis. We report a case of alveolar soft part sarcoma involving the tongue
      base in an adolescent female. She underwent laser assisted excision of the tongue
      base tumour followed by post-operative radiotherapy. The clinical presentation,
      histopathological picture, immunohistochemical & cytogenetic studies, radio
      imaging, management protocols and prognosis of this tumor have been discussed.

PMID- 23120486
TI  - Pleomorphic adenoma of the base tongue.
AB  - Pleomorphic adenoma is the benign tumor of salivary glands. The cells of origin
      are the myoepithelial cells and intercalated duct cells. This tumor is more
      common in major salivary glands. A rare case of pleomorphic adenoma of the minor
      salivary glands of base tongue is reported here. It was surgically excised by a
      median mandibulotomy approach and patient is free of any recurrence in one-year
      follow-up.

PMID- 23120487
TI  - Tooth in a cyst - Is it always a dentigerous cyst?
AB  - We present the case report of an 18-year-old female patient who presented with
      unilateral nasal obstruction. Computed tomography scanning revealed an unerupted
      molar in the posterior wall of the right maxillary sinus with a cystic swelling
      in the sinus. The preoperative diagnosis was a dentigerous cyst. The patient
      underwent endoscopic removal of the cyst and tooth. The operative findings and
      histopathology showed that it was an odontogenic keratocyst. This paper stresses
      the importance of diagnosing this condition and that a tooth in a cyst is not
      always dentigerous.

PMID- 23120488
TI  - Functional study of nasal mucosa in endoscopic sinus surgery and its correlation
      to electron microscopy of cilia.
AB  - The effect of functional endoscopic sinus surgery (FESS) was evaluated in 20
      patients with chronic sinusitis. The physiological function of sinus mucosa and
      its mucociliary transport mechanism was assessed pre and post operatively in
      patients undergoing FESS by performing Saccharin clearance test. The effect of
      functional sinus surgery on nasal mucosa was evaluated using scanning electron
      microscopy and study of the ultrastructure of cilia in pre and post operative
      patients and correlation with histopathological examination. The mucociliary
      transport mechanism of the sinus mucosa improved 6 weeks following surgery.
      Histopathologically there was evidence of improvement in the ciliary population
      and decrease in inflammation, ulceration, fibrosis, vascular congestion, edema,
      squamous cell metaplasia, basement membrane thickening and polyp formation in
      comparison to the diseased mucosa sampled preoperatively. Scanning electron
      microscopic examination revealed considerable increase in the ciliary area as
      well as the orientation of cilia. Subjective improvement 6 weeks following
      surgery was confirmed by decrease in saccharin test time. This study revealed
      that FESS is an effective surgical procedure in chronic sinusitis and improves
      the overall function of the sinuses.

PMID- 23120489
TI  - Benign laryngopharyngeal lesions: a case series.
AB  - Benign neoplasms of the laryngopharynx are extremely rare. Hereby we present 3
      such interesting cases managed at our institute. While one was managed by
      conventional endoscopic route the other two required external approach. Even in
      the present era of endoscopic surgery sometimes these lesions necessitates
      external approach owing to anatomical distortion causing difficulty in intubation
      and/or inadequate exposure of the lesion. All these cases highlights the need of
      a competent surgeon to treat benign laryngopharyngeal lesions.

PMID- 23120490
TI  - Fallopian canal dehiscence: can it be pridicted.
AB  - The aim of the study is to give an idea about true incidence and most common
      location of fallopian canal dehiscence and to identify predictive factors
      associated with fallopian canal dehiscence based on preoperative and peroperative
      clinical correlates so as to facilitate preemptive prediction of the condition.
      The study design pertains to a prospective study. The setting of the study was
      tertiary referral hospital and a total of 146 patients underwent radical and
      modified radical mastoidectomy as primary procedure between Jan. 2003 to Dec.
      2004. The site of dehiscence and associated pre-operative and per-operative
      findings were noted. Our results showed the incidence of fallopian canal
      dehiscence among cases undergoing radical and modified radical mastoidectomy was
      82/1000 per year. Around 66.6% dehiscence was located in tympanic segment. The
      preoperative factors significantly associated with the fallopian canal dehiscence
      (p< 0.05) were Aural polyp, Extra-cranial complications, Cholesteatoma and Facial
      palsy. Per-operative findings were Cholesteatoma, All ossicles necrosed except
      stapes footplate and Lateral semicircular canal fistula.

PMID- 23120491
TI  - Extracorporeal septoplasty-how we do it at marienhospital stuttgart germany.
AB  - Septoplasty is one of the most common surgery of ENT but even today the difficult
      septum still presents a great surgical problem. A severe septum deformity is
      usually due to an accident quite often in childhood. It is also seen in patients
      with malformation such as cleft lip and cleft palate deformity. It affects not
      only the nasal function, but also the aesthetic part of the nose. Severe septal
      deformities can not be corrected properly by the standard septoplasty techniques.
      Therefore in such cases an extracorporeal septoplasty is recommended. In this
      technique the whole septum is taken out, the bony and cartilaginous septum in one
      piece if possible, a new septal plate is reconstructed by different surgical
      techniques, followed by replantation and reconstruction of the cartilagenous
      dorsum. The first author kept on improving the safe septal fixation, rebuilding
      of cartilagenous dorsum and overall the extracorporeal septoplasty technique over
      the period of time and this technique with all its refinement can be recommended
      to all the surgeons dealing with this challenging noses.

PMID- 23120492
TI  - The mini-rhino-conjunctivitis quality of life (qol) questionnaire (mrqlq) - self
      administered.
AB  - OBJECTIVE: Our aim was to administer the MRQLQ Questionnaire in Indian adults
      with allergic rhino-conjunctivitis (ARc).  CRITERIA FOR INCLUSION IN THE STUDY:
      Adults with chronic ARc, with sufficiently troublesome current symptoms,
      attending The Allergy Clinic of The Hinduja Hospital, Mumbai, during March-August
      2006 were selected. RESULTS: The five highest PS were seen with sneezing 290,
      irritation 238, running nose 228, stuffy nose 220, anxiety 203 and interrupted
      working 203. The 5 lowest PS were seen with disturbed sleep 83, dry throat 98,
      affected walking for 1/2 kilometre 98, do not sleep deeply 103 and phlegm 105.
      DISCUSSION: The five highest PS were due to symptoms of rhinitis, general
      irritation, anxiety & interruption of work. Thus rhinitis itself affects QOL. The
      5 least PS were mainly sleep-related. CONCLUSION: We have applied the MRQLQ on
      Indian patients with ARc. We could obtain a product score for every item in it,
      on the basis of which we could classify the degree of its effect on his QOL. PS
      was highest in rhinitis-related symptoms. 2 Emotions related and 1 Role
      limitation item gave moderate PS, while all PS in eye related, Physical
      functioning, Social functioning, Sleep-related & Other Symptoms items were in the
      mild range. Larger data sample is needed to validate and show its discriminatory
      power.

PMID- 23120493
TI  - Role of dynamic MR imaging in obstructive sleep apnoea.
AB  - The purpose of this study is to assess the role of dynamic MR imaging in the
      evaluation of obstructive sleep apnea. In this prospective study, MRI was
      performed in 22 patients (eighteen male and four female, ranging in age from 26
      to 70 years) suspected of having obstructive sleep aponea (OSA). 18 of them had a
      polysomnography study prior to MRI evaluation, which confirmed the presence of
      OSA. Positive cases were classified according to anatomic location and cause of
      narrowing. Patients with isolated retropalatal narrowing on MRI were advised
      uvulopalatopharyngoplasty (UPPP). Two patients had normal findings on MRI, 8
      patients had retropalatal narrowing, five had retroglossal narrowing and seven
      had narrowing at multiple levels. All twenty-patients had collapse of lateral
      pharyngeal wall. Four patient with isolated retropalatal narrowing, who underwent
      UPPP after MRI evaluation were found to be cured on 6 month postoperative follow
      up.Dynamic MR imaging can accurately diagnose the cause and level of upper airway
      narrowing in patients with OSA. It can characterize and anatomically classify the
      level of narrowing for planning reparative surgery.

PMID- 23120494
TI  - Is surgical vestibular ablation necessary in disabling peripheral vertigo?
AB  - The use of intratympanic gentamicin is an easily performed office procedure for
      the conservative treatment of the Meniere's disease patient who has failed
      medical therapy. The procedure provides excellent control for the symptom of
      vertigo and is one of the most successful methods in the treatment of vertigo due
      to inner ear disorders. Surgical ablation is no longer necessary for adequate
      control of vestibular symptoms and that chemical ablation/alteration may replace
      the need for surgical vestibular ablation in cases of disabling Meniere's disease
      and other inner ear causes for peripheral vertigo.

PMID- 23120495
TI  - Altered clinical course of glomus tympanicum - a case report.
AB  - Glomus tumours of temporal bone are rare and usually present with symptoms of
      hearing loss and tinnitus. Diagnosis is often delayed due to the slow growth of
      the tumour. Here we present a case report of a patient diagnosed as glomus
      tympanicum who presented only with unilateral progressive hearing loss for the
      past one year and rapidly detoriating hearing loss since two months who was
      managed successfully.

PMID- 23120496
TI  - Occult foreign bodies in the aero digestive tracts in infancy.
AB  - Foreign body impaction in aero digestive tract in infancy is difficult to
      diagnose sometimes. In this review of five unusual cases of occult foreign body
      impaction in aero digestive tract has been presented and their management
      discussed.

PMID- 23120497
TI  - Recurrent odontogenic myxoma of maxilla: a diagnostic and operative dilemma.
AB  - Odontogenic myxoma of maxilla is a very rare occurrence. It is a slow growing
      benign, locally malignant tumor notorious for recurrence. Hereby we present a
      case of recurrent odontogenic myxoma of the maxilla in a 32-year-old male managed
      surgically by partial maxillectomy. The diagnostic and operative dilemmas
      encountered while managing the case are discussed in detail.

PMID- 23120498
TI  - Papillary carcinoma in submandibular region - a diagnostic dilemma.

PMID- 23120499
TI  - Bilateral arytenoidectomy with lateralisation of vocal folds: review of two
      cases.
AB  - We present a review of two cases of bilateral abductor palsy of vocal cords with
      cords in paramedian position. The aetiology was not clear. As definitive
      treatment, arytenoidectomy and vocal cord lateralization on both sides were done
      by external laryngofissure approach. Objective of this review is to emphasize
      upon the fact that external procedures under direct vision has still a role to
      play in the era of endoscopic maneuvers. It can be performed successfully even at
      centers having limited gadgets. The two procedures of arytenoidectomy and vocal
      cord lateralization were combined to achieve higher success rate irrespective of
      fixity of cords. Result seems to be at par with other newer surgical modalities.

PMID- 23120500
TI  - Atypical angiofibroma of larynx - a case report.
AB  - Primary extra nasopharyngeal angiofibroma of larynx is a very rare tumour. We
      here by present a case of angiofibroma of larynx affecting the anterior
      commissure & subglottic region in larynx-a rare site of involvement.

PMID- 23120501
TI  - Schwannoma of larynx - a rare presentation.
AB  - Neurogenous tumours of the larynx are extremely uncommon. Schwannoma of larynx is
      a variant of neurogenous tumour. The patient underwent microlaryngoscopic
      excision of that tumour. We present here the clinical findings of the case, along
      with direct laryngoscopic view, the photograph of the mass after removal and
      histological slide compatible with the diagnosis of schwannoma.

PMID- 23120502
TI  - Subcutaneous emphysema: A least common presentation of foreign body bronchus.
AB  - Foreign bodies in air way are common days occurrence in Otolaryngologic practice
      but widespread subcutaneous emphysema extending form scalp to scrotum is a rare
      entity in foreign body bronchus. As rarity is, a novelty hence reported.

PMID- 23120503
TI  - Haemangioma or vascular malformation of the tympanic membrane? a case report and
      review of literature.
AB  - Benign vascular lesions are rarely found on the tympanic membrane. We report a
      case of such a lesion in a novel location, with review of the relevant
      literature. We also highlight the significance of accurate classification of such
      lesions, proposing adoption of more pathophysiologically-correct nomenclature of
      "haemangioma" and "vascular malformation".

PMID- 23120504
TI  - Orbital apex syndrome in a child.
AB  - A 8-year-old male presented with visual loss, diplopia, ptosis, pain behind the
      left eye, facial numbness and vomiting of one week duration. The
      ophthalmological, neurological and radiological examination showed a lesion of
      the left orbital apex with extension into the cavernous sinus. Examination of the
      nose and paranasal sinuses did not reveal any abnormality. Transnasal Endoscopic
      orbital decompression was performed and inflamed granulation tissue found in the
      orbital apex was removed. Microbiology showed fungal elements which on culture
      grew Aspergillosis flavus. Antifungal therapy with new generation oral drug
      (voriconazole) resulted in complete resolution of symptoms. Relevant literature
      is reviewed and discussed.

PMID- 23120505
TI  - Internal jugular vein thrombosis in a case of attico antral disease - a rare
      presentation in this modern antibiotic era.
AB  - We report a case of Internal Jugular Vein Thrombosis with a long segment thrombus
      in a clinical setting of attico antral type of Chronic Suppurative Otitis Media
      (CSOM) in a 20 year male. He presented with hectic rise of temperature with
      chills & rigor of 7 days duration associated with left ear discharge & throbbing
      headache of 10 days duration. ENT examination revealed attico antral type of
      Chronic suppurative Otitis Media with sinus thrombophlebitis. Further
      investigations revealed a mural thrombus extending from the lower part of
      Internal Jugular Vein (IJV) till the Torcula Herophili. Left Modified radical
      mastoidectomy with exposure of transverse & sigmoid sinus was done to completely
      eradicate the disease and source of infection. The patient was treated with oral
      anticoagulants and parenteral antibiotics based on the sensitivity report and
      became asymptomatic after 8 weeks.

PMID- 23120506
TI  - Giant fibrous epulis.
AB  - A variety of swellings located on or near the gums is clinically included under
      the heading of epulis. There are various types of epulis. In today's era of super
      specialization gum swellings more commonly present to the dental surgeon than to
      the practicing otolaryngologist. We present an interesting case of a fibrous
      epulis managed in our institute along with a brief review of literature.

PMID- 23120507
TI  - Bilateral nasal vestibular stenosis: a case of rhinoscleroma and review of
      surgical techniques.
AB  - Vestibular stenosis is an uncommon but debilitating cause of nasal obstruction.
      It is caused by disruption of the nasal vestibular lining with secondary
      proliferation of granulation and fibrous tissue. A number of techniques have been
      described for repair of the stenotic segment. Correction can be difficult because
      of the tendency of wound contracture and recurrence. We present a surgical
      technique that employs the concept of excision of the stenotic segment,
      enlargement of the vestibule and placement of a full thickness skin flap. Its
      ability to resist contracture obviates the need for post-operative stenting and
      gives good result.

PMID- 23120508
TI  - Wegener's granuloma - a case report.
AB  - A 75-year-old man presented with nasal obstruction, purulent nasal discharge,
      crusting and a reddish ulcerated swelling over nose and upper lip. There was
      external nasal deformity. Histology of the lesions showed necrotic granulomatous
      vasculitis. There was no other systemic involvement. ANCA test was negative. The
      patient responded well to prednisolone and cyclophosphamide.

PMID- 23120509
TI  - Isolated palate ulcer due to mucormycosis.
AB  - Mucormycosis is a rare but serious fungal infection that rapidly attacks and
      kills its untreated victims, who are often immunocompromised. It is one of the
      most fulminant and often fatal mycotic infections known to human beings.
      Rhinocerebral mucormycosis is the commonest presentation and its extension to the
      orbit and brain is quite usual but the palatal involvement is a rare and late
      occurrence. Isolated location of mucormycosis on the palate in an immunocompetent
      host is an unusual clinical entity. Here we report a case of deep hard palate
      ulcer due to mucormycosis in a 56-year-old man without any predisposing factor.
      He was successfully treated with a combination of surgical debridement and
      systemic liposomal amphotericin B administration for six weeks. By presenting
      this case report we would like to emphasis that mucormycosis should be included
      in the differential diagnosis of the hard palate ulcers even in immunocompetent
      patient.

PMID- 23120510
TI  - Unusual presentation of nasopharyngeal carcinoma - a case report.
AB  - Nasopharyngeal carcinoma may present with bewildering arrays of signs & symptoms.
      Diagnosis often become difficult and requires a high degree of clinical suspicion
      for the disease. We here by present a case of 11 year old girl which have unusual
      presentation.

PMID- 23120511
TI  - Tuberculosis of paranasal sinuses.
AB  - Nasal tuberculosis is very rare but much rarer is tuberculosis of paranasal
      sinuses. It involves especially the maxillary sinus and is usually unilateral. We
      report an unusual case of tuberculosis of frontal and maxillary sinus in a 68
      years old male, who presented with a swelling above left medial canthus, with no
      other eye or nasal complaints. Clinical and radiological findings on our initial
      evaluation suggested that the patient had left frontal mucocoele with bilateral
      maxillary haziness. Diagnosis was established on FNAC report and subsequent Ziehl
      - Neelsen staining of nasal swabs and tuberculin skin test. Later chest x-ray
      examination was suggestive of pulmonary tuberculosis, which was the primary
      cause. Patient responded well to antituberculosis drug therapy.

PMID- 23120512
TI  - An unusual foreign body in the paranasal sinuses.
AB  - We report a case of 38-year-old male who was reffered from eye OPD with a
      retained foreign body in the periobita of Rt eye extending into the Rt ethmoid
      and sphenoid sinuses after six months of injury. The foreign body was removed
      through external ethmoidectomy and incision on the periorbita of Rt eye.

PMID- 23120513
TI  - Staghorn rhinolith in nasopharynx: an unusual case.
AB  - The present case report is of a young female with complaint of foul smelling
      nasal discharge normal anterior rhinoscopic findings and an irregular mass on
      digital palpation of nasopharynx, confirmed by NCCT and extracted through oral
      route.

PMID- 23120514
TI  - Simultaneous complete branchial and thyroglossal fistula - a rare presentation.
AB  - The anomalies of branchial cleft and thyroglossal tract accounts for the majority
      of fistulas in head neck region. A simultaneous presentation of both type of
      fistula in a same patient is very rare with no such cases reported in Indian
      literature till date. Here we present a case of simultaneous complete branchial
      and thyroglossal fistula in a 13-year-old girl with radiologically demonstrable
      internal opening on fistulogram managed surgically.

PMID- 23120515
TI  - Evolution of rhinology.
AB  - The study of the nose is as old as civilisation. Various conditions affecting its
      structure and function has been documented in Edwin Smith Papyrus in hieroglyphic
      script, an Egyptian writing system of the mid -4th Millennium BC.The major
      contribution for the complete reconstruction of the nose originated in India by
      Sushruta in around 600 BC. Writing in Sanskrit in the form of verses he described
      in detail the technique of total reconstruction, which is still being practiced
      today as Indian Rhinoplasty. This surgical reconstruction paved the way to modern
      plastic surgery in Europe and United States in 18th century. Sushruta contributed
      not only to the plastic surgery of the nose, but described entire philosophy of
      Head and Neck and other surgery as well. Other notable contributors were Greek
      physicians, Hippocrate and Galen, and at the birth of the Christianity, Celsus
      wrote eight books of medical encyclopaedia, which described various conditions
      affecting nose.Septal and Sinus surgery, in comparison to rhinoplasty did not
      develop until 17th century. Septal surgery began with total septectomy, sub
      mucous resection by Killian & Freer in early 20th century and later septoplasty
      by Cottle in middle of 20th century.Sinus surgery probably originated in Egypt,
      where instruments were used to remove brain through the ethmoid sinuses as part
      of the mummification process. In 18th century, empyema of the maxillary sinus was
      drained through the tooth socket or anterior wall of the sinus, which lead to the
      evolution of radical procedures of removal of mucous membrane and inferior meatal
      antrostomy. In the late 20th century, improved understanding of the mucociliary
      mechanism described by Prof. Messerklinger and Nasal Endoscopy described by Prof.
      Draf with the development of fibre optics and CT imaging, heralded a new era,
      which evolved in functional endoscopic sinus surgery. New technology further
      enhanced the scope of endoscope being used "around and beyond" the nose.

PMID- 23120516
TI  - Pediatric cochlear implantation - II: postoperative follow-up.
AB  - A child with a cochlear implant is expected to achieve the successful outcome of
      facilitated perception of sound and more oral communication. To achieve this
      goal, ongoing intervention from a variety of professionals is required. These
      professionals may represent the disciplines of medicine, audiology, social work,
      education, and speech / language pathology. In India, cochlear implantation is
      available in only a few large cities. Here, the otolaryngologist will direct the
      cochlear implant program. Besides determination of medical candidacy, device
      implantation and medical management, the otolaryngologist is responsible to
      ensure that other aspects of cochlear implant management are implemented. This
      paper, the second of two that describe the multidisciplinary, team approach of
      the Pediatric Cochlear Implant Program of The Children's Hospital of Philadelphia
      (CHOP), in Pennsylvania, USA, discusses the non-medical aspects of cochlear
      implant post-implantation follow-up. The first article, previously published,
      discussed cochlear implant candidacy. The various speech tests used at CHOP for
      assessment are based on the English language. They may be translated into the
      regional Indian languages where the assessment and training can be carried out
      accordingly.

PMID- 23120517
TI  - Nasal polyps: a clinical, histopathological and radiological profile.
AB  - OBJECTIVE: Comparison of clinical, radiological & histopathological profile in
      nasal polyps.  MATERIAL #ENTITYSTARTX00026; METHOD: A prospective randomized
      study conducted on 50 patients of nasal polyps (diagnosed clinically or
      radiologically) from July 2003 to December 2005 selected from the inpatient
      department of Otorhinolaryngology, Dayanand Medical College & Hospital, Ludhiana.
      RESULTS: The results show that 70% of the clinical findings were consistent with
      radiological findings. However in rest 30% of cases, a difference of opinion was
      seen in non neoplastic and neoplastic lesions. The diagnosis of allergic fungal
      or allergic non fungal can only be established on histopathology. CONCLUSION: It
      is concluded that for proper evaluation of nasal polyps clinical, radiological
      and histopathological evaluation should be done in all the patients, where
      radiology provides a road map to the endoscopic surgeons and warns of any
      existing or impending complications. Histopathology always gives a confirmatory
      diagnosis.

PMID- 23120518
TI  - Paranasal sinus mucoceles: a comprehensive retroprospective study in Indian
      perspective.
AB  - Paranasal sinus mucoceles are the most common expansile lesion of the paranasal
      sinuses. Hereby we present a comprehensive retroprospective study on the
      paranasal sinus mucoceles in our geographic area which is very significantly
      lacking till now which we hope would immensely help comparative analysis and
      management in near future.

PMID- 23120519
TI  - Recovery profile of patients undergoing nasal surgical procedures: a comparison
      between sevoflurane and propofol.
AB  - OBJECTIVES: To compare the recovery profile of sevoflurane and propofol in nasal
      surgical procedures. DESIGN: A prospective, double blind, randomized study
      SETTING: King Abdul Aziz University Hospital, Riyadh, Saudi Arabia, a tertiary
      care teaching hospital, attached with King Saud University, Riyadh Saudi Arabia.
      PATIENTS: 60 ASA I-II patients age between 18-35 years, and weighing 50-80 kg,
      scheduled for nasal surgical procedures. METHODS: Patients were assigned randomly
      to one of the two groups, the Sevoflurane Group-S (n = 30) & the Propofol Group-P
      (n = 30). Anesthetic induction was carried out using propofol 2.0mg/kg.in both
      the groups. Cis-atracurium 0.15mg/kg was given for intubation. Airway was
      protected with a throat pack around the endo-tracheal tube. Fentanyl
      1microgram/kg was given as bolus followed by infusion at a rate of 1
      microgram/kg/ hour. Anesthesia was maintained with sevoflurane 2% in Group-S, and
      propofol infusion at a rate of 200 microgram/kg/min. in Group-P. 50% oxygen in
      nitrous oxide was given in both the groups. At the end of surgery, patients were
      extubated after reversal of the neuromuscular block. Immediate recovery was
      assessed by recording the time to breathe spontaneously, time to extubation, and
      time of spontaneous eyes movements from the time of giving reversal. Ketoprofen
      1.5mg/kg intramuscularly was given to all patients before transfer to (PACU). In
      PACU, sedation score was assessed for 45 min. Intermediate recovery was assessed
      by TDT and DSST at 15, 30 and 45 min. Time taken to state name and father's name
      was recorded. RESULTS: Patients in Group-S breathed significantly earlier than
      those in Group-P. Group-P showed significantly better performance with TDT at 45
      min and with DSST at 30 and 45 min. CONCLUSIONS: We conclude that both
      sevoflurane and propofol provide early and comparable post anesthesia recovery
      for patients undergoing nasal surgical procedures.

PMID- 23120520
TI  - Fine needle aspiration biopsy of intra-osseous lesions of the mandible and
      maxilla.
AB  - This study was done with an aim to assess the reliability and diagnostic accuracy
      of fine needle aspiration biopsy of intraosseous jaw lesions. Of the 42 cases,
      adequate material for cytologic evaluation was obtained in 35 cases. Malignant
      cells were found in 9 of 35 cases. FNAB diagnosis was confirmed by histopathology
      in all 9 of these specimens (100% accuracy). The FNAB diagnosis of benign lesions
      was confirmed in 19 of 26 cases (73% accuracy). The most common benign lesions
      were odontogenic cysts, followed by fibro-osseous and giant cell lesions.
      Incorrect diagnosis was related to lack of architectural context of the FNAB
      material, inadequate quantity of the aspirate and sampling of a non
      representative part of a large lesion. Thus FNAB is a useful, simple, fairly
      reliable and outpatient procedure for diagnosis of intra-osseous jaw lesions,
      especially to distinguish between malignant and benign jaw lesions.

PMID- 23120521
TI  - Role of rhinomanometry to assess nasal airflow and resistance in patients
      undergoing septoplasty.
AB  - Nasal obstruction is a common symptom. Rhinomanometry is a tool to objectively
      assess the nasal airway. A prospective study was undertaken to assess the nasal
      airflow and nasal resistance in 25 patients of deviated nasal septum undergoing
      septoplasty using rhinomanometry preoperatively and postoperatively.
      Rhinomanometric improvement in nasal airflow and decreased nasal resistance were
      found in 88% patients after surgery.

PMID- 23120522
TI  - Missile injuries in head - neck and maxillo-facial region - an experience in
      eastern nepal.
AB  - Ballistic injuries to head-neck and maxillofacial region is quite common problem
      nowadays. Most of the time the injuries seem to be dreadful but the mechanism of
      the injuries caused by ballistics and the anatomical conditions of maxillofacial
      and head-neck region mitigate the severity of the injuries. Proper primary
      management followed by reconstruction and management of associated injuries
      decreases the mortality and morbidity of missile injuries in head-neck and
      maxillofacial region. Eleven cases of missile injuries in head-neck and
      maxillofacial region are included in the present study. The mechanism of the
      injury and the ideal management strategy for the ballistics injuries in the
      region has been discussed in the article.

PMID- 23120523
TI  - Tone-evoked brainstem responses and auditory steady state responses to 40hz and
      80hz amplitude modulated stimuli with different frequencies - a comparative
      study.
AB  - Tone burst evoked auditory brainstem responses and auditory steady state
      responses with 40 or > 80 Hz modulation can be used to determine frequency
      specific threshold. AIM: The present study was taken up to check for the efficacy
      of estimating hearing thresholds by tone burst ABR and ASSR. The frequency effect
      (low, mid and high) on estimating the threshold was also focused upon. METHODS:
      20 normal hearing adults (40 ears) in the age range of 16 to 30 years
      participated in the study. The pure tone audiometry and immittance was initially
      done. Subsequently, tone-burst ABR, 80Hz ASSR and 40Hz ASSR to estimate the
      threshold with three frequencies 500Hz (low), 2000Hz (mid) and 4000Hz (high) was
      done. The data was analyzed statistically using pair sample t-test. RESULTS: ASSR
      threshold for 80Hz and 40Hz was almost comparable. ASSR was superior to estimate
      the threshold than tone-burst ABR. For the low frequency the discrepancy between
      the behavioral threshold and frequency-specific evoked audiometry was more when
      compared to mid and high frequency. CONCLUSION: Present study showed that steady
      state responses were efficient means of threshold detection than visual detection
      of ABR wave-V. In awake adult subjects, 40Hz and 80Hz amplitude modulated
      produced similar results. For the threshold estimation ASSR was better than tone
      burst ABR.

PMID- 23120524
TI  - Posterior cricoid split with costal cartilage augmentation for high subglottic
      stenosis.
AB  - BACKGROUND: Stenosis of the upper subglottis presents special problems. Its
      vicinity to the vocal folds leads to a high incidence of vocal fold fixation, and
      also precludes surgical treatment by cricotracheal resection and anastomosis
      OBJECTIVE: To describe the experience with posterior cricoid split and insertion
      of free costal cartilage graft in the treatment of high subglottic stenosis and
      posterior commissure glottic stenosis. SETTING: Tertiary care university
      hospital. METHODS: Four cases with Grade III/ IV high subglottic stenosis/
      posterior commissure glottic webbing recalcitrant to previous surgical therapy
      treated with posterior cricoid split and insertion of free costal cartilage graft
      by a laryngo-fissure approach. Temporary airway stenting for 4 months post
      surgery with a silicone T-Tube. RESULTS: Successful restoration of the airway and
      decannulation in all 4 cases. CONCLUSION: Grade III or IV stenosis of the upper
      half of the subglottis is successfully treated in a high proportion of patients
      with posterior cricoid split and augmentation with costal cartilage free graft.

PMID- 23120526
TI  - Sinonasal neuro endocrine carcinoma extending into orbit - a case report.
AB  - Small Cell Neuroendocrine Carcinomas of the Sinonasal tract are extremely
      uncommon and distinct neoplasms with aggressive clinical behavior. They have
      similar morphological and immunohistochemical features to those of small cell
      carcinomas of the lung. They should be distinguished from Olfactory
      Neuroblastomas. We report a case of this rare entity.A 46-year-old woman
      presented with a history of injury to the right eye with facial pain and
      proptosis as the primary symptoms. Later she developed nasal stuffiness. C.T.
      Scan revealed a space occupying lesion in the right nostril extending into
      ethmoid sinus and orbit. Functional endoscopic sinus surgery was done with
      decompression of the orbit. The biopsy material was obtained from ethmoid sinus
      and orbit. Histopathological examination of the biopsy specimen along with
      Immunohistochemical stains confirmed a Small Cell Neuroendocrine Carcinoma.
      Patient was treated with Radiotherapy and chemotherapy and responded well.

PMID- 23120525
TI  - The role of functional endoscopic sinus surgery (FESS) in patients with asthma
      with chronic sinusitis.
AB  - 25 patients of bronchial asthma with chronic sinusitis were operated with the aim
      to evaluate the efficacy of functional endoscopic sinus surgery (FESS) on asthma
      symptoms. The mean postoperative daytime asthma symptom scores, nocturnal asthma
      symptom scores, mean postoperative nocturnal awakening scores and number of
      asthma attacks reduced significantly (p<0.001). The mean FEV(1) observed
      postoperatively showed significant increase (p<0.001). 21 patients reported
      overall significant improvement in the asthma. 6 patients were completely taken
      off from all sort of anti-asthmatic drugs [inhalational corticosteroids (ICS) +
      long acting beta(2) agonist (LABA) ]. In 3 patients there was significant /
      substantial decrease in the dosage of anti-asthma drugs. It is concluded that
      FESS is a viable option for improving the control of asthma.

PMID- 23120527
TI  - Rhiinosporidiosis - unusual presentations.
AB  - Rhinosporidiosis is an infection caused by Rhinosporidium seeberi that frequently
      presents as polypoidal nasal lesions. Here, we report two cases of
      rhinosporidiosis with unusual presentations. The first case presented in our
      department with chronic dacryocystitis of left side for endoscopic
      dacryocystorhinostomy (endoscopic DCR) operation. The second case presented as a
      long hanging mass arising from the right side of nasal septum. The diagnosis was
      established on the morphological basis by the identification of endospores and
      sporangia. The clinicopathological and immunologic features were discussed and
      the literature was reviewed.

PMID- 23120528
TI  - Clear cell predominant epithelial-myoepithelial carcinoma of the hard palate -
      role of immunohistochemistry.
AB  - Epithelial-myoepithelial carcinoma (EMC) arising from the minor salivary gland of
      the hard palate is very rare. A 34-year-old lady presented with a nodular
      swelling in the hard palate. Histopathologically, a diagnosis of clear cell
      predominant EMC was suggested. Immunohistochemistry demonstrated the biphasic
      nature of the tumor and confirmed the diagnosis of EMC.

PMID- 23120529
TI  - Synovial sarcoma of unusual site treated with chemo-radiation.

PMID- 23120530
TI  - Migrating implant masquerading as acute sinusitis.
AB  - The author presents a case of migrating miniplate screw presenting as acute on
      chronic sinusitis. Mini plates have been used in osteosynthesis of the mandible
      and maxillofacial surgery. In the last decade there has been an increase in the
      incidence of use of miniplates to stabilise Lefort II and III fractures involving
      the maxilla. The case report highlights the rare presentation of screw impinging
      on inferior turbinate in a patient who is a known case of chronic sinusitis
      presenting as acute sinusitis with dramatic relief of symptoms on removal of the
      implant.

PMID- 23120531
TI  - Ramsay hunt syndrome in a person with HIV disease.
AB  - We report a case of 45-yr-old HIV positive male who presented with herpes zoster
      oticus at the time of diagnosis of his HIV status. The patient had vertigo,
      painful vesicular eruptions on the right ear and unilateral sensorineural hearing
      loss. The etiology, diagnosis and treatment of herpes zoster are discussed in
      detail in this report. We report this case to raise awareness among the general
      practitioners to investigate for HIV when they diagnose cases of herpes zoster.

PMID- 23120532
TI  - Malignant myoepithelioma of the parapharyngeal space - a case report.
AB  - Malignant myoepithelioma (MM) of parapharyngeal space provide both a diagnostic
      and therapeutic challenge. Malignant myoepitheliomas are rare tumour of salivary
      glands. Most occur in the parotid gland, few other sites of origin are described.
      Malignant myoepithelioma of the parapharyngeal space are extremely rare with only
      a few cases has been reported. We present a case of malignant myoepithelioma in
      the parapharyngeal space and discuss its diagnostic and therapeutic aspects.

PMID- 23120533
TI  - Arteriovenous malformation of the external ear.
AB  - Arteriovenous malformation (AVM) involving the external ears is relatively
      uncommon in adults. Arteriovenous malformations typically present during
      childhood and rarely manifest during adulthood in the head and neck region.
      Symptomatic arteriovenous malformations often pose difficult therapeutic
      challenges. We report a case of large arteriovenous malformation of the external
      ear in a 21-year-old female.

PMID- 23120534
TI  - Myopericytoma of neck region - A case report.
AB  - A 42-year-old male presented with a history of an enlarging painless swelling on
      the right side of neck for 15 days. It recurred within three months of partial
      excision. Immunohistochemistry showed positivity for Smooth Muscle Actin [SMA].
      This newly described entity is being reported for its unusual histological
      features and its differential diagnosis with other spindle cell and vascular
      lesions of soft tissues.

PMID- 23120535
TI  - Foreign body oesophagus in neonate with unusual presentation.
AB  - Children up to the age of 6 years present commonly in the ENT Department with the
      foreign bodies in the aero-digestive tract. The most common foreign body is coin
      in the cricopharynx. But it is rare to see foreign body in neonate. Authors have
      come across with a rare case of foreign body oesophagus in neonate causing
      obstructive symptoms to both respiratory and food passages after homicidal
      attempt.

PMID- 23120536
TI  - Cricopharyngeal achalasia - a rare cause of dysphagia.
AB  - Cricopharyngeal achalasia is a rare clinical entity in which upper esophageal
      sphincter (cricopharyngeus) does not open adequately during swallowing leading to
      dysphagia. Barium swallow reveals a smooth posterior impression of
      cricopharyngeus at C6 level. We report cricopharyngeal achalasia in a 68 year
      male who was managed with dilatation.

PMID- 23120537
TI  - Laryngeal schwannomas-case reports with rare presentations.
AB  - Schwannomas also known as Neurilemmomas are benign encapsulated, slow growing
      perineural tumours of Neuro-ectodermal origin that arise from the sheet of
      schwann cells. Two cases are being presented due to their rarity and in both
      cases the diagnosis was arrived at after the excision of the tumour.

PMID- 23120538
TI  - Hydatid cyst in submandibular salivary gland.
AB  - This case of 52-year male with swelling in the left submandibular area for 1 year
      came to ENT OPD of Patna medical college, Patna. Clinical examination showed
      swelling to be multiple nontender cysts with enlarged submandibular salivary
      gland. CT-scan revealed large well-defined encapsulated multicystic lesions in
      the left submandibular gland. FNAC was suggestive of aspirate to be ectopic to
      that area. Excision biopsy was done. HPE showed features suggestive of parasitic
      infestation along with chronic sialadenitis. Gross picture and investigations
      were highly suggestive of parasitic infestation to be primary hydatid cyst of the
      gland. Scanning for other areas like liver and lungs done, no lesion was found.

PMID- 23120539
TI  - Orbital hydatid cyst - A rare case report.
AB  - We present a rare case of cystic hydatid disease of orbit and its endoscopic
      management. A 35-year-old female patient presented with unilateral progressive
      nonpulsatile proptosis of the right eye. Ophthalmological examination revealed
      proptosis of right eye with complete visual loss. Hydatid cyst of the orbit is a
      rare cause of proptosis, which can be safely managed endonasally in selected
      cases and by albendazole chemotherapy.

PMID- 23120540
TI  - Lipoma of the deep lobe of parotid gland - a case report and review of
      literature.
AB  - Lipoma of deep lobe of parotid gland is a rare clinical entity. Less than 10
      cases have been reported in the literature in our knowledge. Because of their
      rarity, they are not often considered in the differential diagnosis of parotid
      tumors. A case of 45-year-old man with an unusually large deep lobe lipoma of
      parotid gland is presented in this article which was surgically managed by total
      conservative parotidectmy. The clinical picture, radiological and
      histopathological features of this entity is being discussed here. Review of
      literature of this clinical situation has been presented in the present article.

PMID- 23120541
TI  - Effect of topical nasal steroid spray in the treatment of non-specific recurrent
      / chronic pharyngitis - a trial study.
AB  - OBJECTIVE: Non-Specific Chronic/Recurrent Pharyngitis is a diagnosis with no
      definite effective treatment. An array of drugs and therapies has been tried from
      local applications like Mandl's paint and throat gargles to anxiolytics. None
      have proved of therapeutic benefit. This trial study is a Pilot study of its kind
      in to the effectiveness of nasal steroid spray in the treatment of non-specific
      chronic pharyngitis. This is a prospective randomized study. SETTING: Study done
      in medical college with ambulatory patients centre. PATIENTS: 53 patients were
      taken up for the study though only 42 could be followed up for a period of 1-2.5
      years. Selection done on the basis of symptoms avoiding extreme age groups and
      subjective persistent relief was central to be considered proof of effectiveness
      of the treatment. Fluticasone Nasal Spray was used in the study. RESULTS: 35
      patients (83.3%) reported some degree of relief in symptoms. 68% had >90% relief
      of symptoms with only a total of 1-2 sprays. There were 7 failures. Side effects
      were negligible. CONCLUSION: Nasal steroid spray is therefore recommended as a
      most cost-effective, safe treatment method for well-selected cases of Chronic Non
      Specific Pharyngitis.

PMID- 23120542
TI  - Lateral temporal bone resection for malignancy of external auditory meatus: our
      approach.
AB  - OBJECTIVE: Surgical management of tumors of the external ear remains
      controversial with regard to the extent of resection and the efficacy of
      piecemeal resection compared to standard en bloc resection. The objective was to
      study the results of lateral temporal bone resection with soft tissue resection
      used at our centre in managing a series of such cases. SETTING: Tertiary referral
      centre PATIENTS: A retrospective study was carried out on seven cases of temporal
      bone malignancies treated at our center, with lateral temporal bone resection by
      the otologic microsurgical technique and superficial parotidectomy, with adjuvant
      radiotherapy where indicated. The mode of presentation, clinical and pathological
      staging, extent of surgical resection, reconstructive methods used and adjuvant
      therapy given were evaluated. The disease free survival on follow-up was noted.
      RESULTS: Disease free survival achieved was comparable with other published
      series, with acceptable morbidity patterns. CONCLUSION: Lateral temporal bone
      resection using otologic microsurgical technique with soft tissue resection is an
      effective way of achieving control of temporal bone malignancies.

PMID- 23120543
TI  - Endoscopic dacryocystorhinostomy with conventional instruments: results and
      advantages over external dacryocystorhinostomy.
AB  - BACKGROUND: The aim of study is to evaluate the Endoscopic dacryocystorhinostomy
      (DCR) with conventional instruments, its results and advantage over external
      dacryocystorhinostomy (DCR). METHODS: The study group comprised of 127 patients
      who underwent consecutive endoscopic dacryocystorhinostomy. The cases operated by
      one team were included in the study to make the uniform analysis and its result.
      There were 48 males and 79 female in this study and male female ratio was 1:1.6.
      The mean age of the patient was 37 years (range from 16 years to 58 years). There
      were wide variety of cases like epiphora, lacrimal sac abscess, lacrimal sac
      fistula, acute dacryocystitis and road vehicular accident. All the patients had
      undergone non-laser, non-powered conventional instruments surgery under local
      anesthesia. The lighted probe was not used in any case for sac identification.
      The free flow of saline through newly created stoma during sac syringing was
      considered as successful criteria. The stent was used in two cases of road
      vehicular accident and in remaining 125 cases no stent was used. There were 66
      cases of epiphora, 30 cases of lacrimal sac abscess, 26 cases of acute
      dacryocystitis, 3 cases of lacrimal fistula and 2 case of road traffic accident
      with multiple fractures. The average follow up period was 17 months (maximum
      follow up 3 years and minimum 4 months.) RESULTS: The success rate was 96 %.
      CONCLUSION: The endoscopic DCR with conventional instruments is safe with very
      high success rate without any complications. It can be done in acute cases and
      very much suited for lacrimal sac abscess and lacrimal sac fistula.

PMID- 23120544
TI  - Laryngocoele: our experince.
AB  - Laryngocoele is an extremely rare condition. Three cases of Laryngocoeles are
      presented. Two cases had infected laryngocoeles. The diagnosis was done
      clinically and confirmed radiologically. No predisposing factor was found except
      in one case who was a singer by profession and initially presented with stridor
      which was an unusual presentation. Surgical excision were done in two cases (case
      1 and 3)and both the case were symptom free.

PMID- 23120545
TI  - Canine fossa approaches in endoscopic sinus surgery - our experience.
AB  - OBJECTIVE: To define the role of canine fossa approach when standard endoscopic
      endonasal sinus surgery technique fails. STUDY DESIGN: Retrospective review of
      all endoscopic sinus surgeries performed from 1992 to 2007. RESULT: Out of 1612
      endoscopic sinus surgeries for various indications, CFA was used in 80 patients
      (4.96%) and among this 15 had bilateral procedure.The various diseases which
      required CFA were allergic fungal sinusitis (AFS), Fungal ball, Chronic invasive
      aspergillosis,antro choanal polyp, inflammatory polyp, Mucocoele and Maxillary
      cyst,inverted papilloma and Juvenile Nasopharyngeal Angiofibroma (JNA). Eight
      patients had minor complications (cheek swelling-6, facial pain-2 ) which
      resolved in 5 days. CONCLUSION: Canine fossa approach offers an ancillary
      approach to failed standard endoscopic endonasal technique thereby avoiding other
      more invasive procedures.

PMID- 23120546
TI  - Management of benign oesophageal strictures in children.
AB  - Managing oesophageal strictures, whether benign or malignant has always been a
      challenging task for ENT Surgeons, Endoscopists, Cardio-thoracic surgeons and
      Gastro-enterologists. Although various newer technological developments have
      helped in better management of malignant strictures, it is the benign strictures
      that are still being managed by conventional means with gum-elastic bougies and
      other dilatation techniques. Children are not immune to benign strictures, rather
      corrosive strictures, congenital webs and membranes etc. are much more common in
      the paediatric age group. We present the technical details and our experience in
      managing benign oesophageal strictures in five children by endoscopic balloon
      dilatation.

PMID- 23120547
TI  - A study of temporal bone fractures.
AB  - Many young adults are now killed and injured in accidents than from another
      causes. More than 75% of these injuries are to the head, and the ear being the
      most frequently injured sensory organ of the body. Temporal bone or basilar skull
      fractures are extremely common in any head injury. Injuries to the temporal bone
      may be considered in three groups: Those affecting the external auditory meatus
      (extralabyranthine fractures), those largely affecting middle ear cleft
      (tympanolabyranthine) and those affecting the internal ear (labyrinthine
      fractures). Many injuries, however, involve all these structures.The sudden onset
      of facial paralysis, vertigo and hearing impairment after a head injury is a
      matter of great concern for the patients and clinicians. Presence of
      cerebrospinal fluid leak (CSF Otorrhoea) can be a challenge for both the
      neurosurgeons and otologists. We hereby present 86 patients of temporal bone
      fractures who presented in the departments of emergency, Neurosurgery or ENT of
      Himalayan Institute of Medical Sciences, Dehradun during last 10 years (1996
      2006).

PMID- 23120548
TI  - Successful treatment of parotid fistula with tympanic neurectomy.
AB  - BACKGROUND: Parotid fistula is a cause of great distress and embarrassment to the
      patient. A host of treatment modalities have been described in past but no
      unanimity exists regarding the most satisfactory of all. Tympanic neurectomy is
      an effective procedure for persistent parotid fistula with no significant side
      effects. OBJECTIVE: To describe our experience with tympanic neurectomy for the
      treatment of persistent parotid fistula and discuss the other treatment
      modalities described. SETTING: Tertiary care referral centre. METHODS: Two cases
      with post traumatic parotid fistula recalcitrant to conservative therapy were
      treated with tympanic neurectomy between 2004-2005. The cases were followed up
      regularly for any recurrence of fistula. RESULTS: Successful and immediate
      cessation of flow from parotid fistula with no recurrence in subsequent followup.
      CONCLUSION: Tympanic neurectomy is a safe and effective procedure for the
      successful treatment of persistent parotid fistula.

PMID- 23120549
TI  - Management of suprastomal tracheal obstruction following : a case report.
AB  - To demonstrate the importance of proper pre operative assessment of
      laryngotracheal stenosis especially if it acquired one. It also demonstrates the
      fact that the available treatment modalities for laryngotracheal obstruction can
      be easily modified as per the clinical presentation for better post operative
      results. Here we present a case of tracheal stenosis following percutaneous
      tracheostomy where there was suprastomal tracheal obstruction which was managed
      in an interesting way to give good post operative results. The obstruction was
      due to impaction of the first tracheal ring in the stoma which was fused to the
      posterior tracheal wall. The obstructing tissue was excised and tracheal lumen
      was established. New tracheostomy was made lower down and the previous stoma was
      closed. By proper pre operative evaluation and assessment of the unique
      pathomechanism of stenosis in this case we could operate the above case by simply
      excicing the obstructing tissue and establishing a lumen instead of resorting to
      other demanding operations for stenosis of larynx that often lead to
      complications.

PMID- 23120550
TI  - Otoplast in the middle ear cleft - a rare complication of hearing aid fitting and
      its surgical management.
AB  - Hearing aid fitment is a routine, usually safe procedure carried out by hearing
      aid technicians or even audiologists. Hearing aids are often considered the
      benign, non-surgical alternative to rehabilitate a patient who cannot be helped
      surgically. It is rare to have to resort surgery to manage a complication
      resulting from hearing aid fitting. We report here, a case of otoplast as a
      foreign body in the middle ear cleft (middle ear cavity and mastoid). The
      otoplast was used to prepare a mould for the hearing aid and the syringe carrying
      the otoplast burst splashing the material into the middle ear and the mastoid.
      This resulted in sudden excruciating pain, further loss of hearing and
      intractable otorrhea. After several attempts to remove the material elsewhere,
      our patient underwent a successful mastoid exploration to remove the otoplast
      resulting in a dry ear after seven years of persistent otorrhea. Patient's
      professional requirement for good hearing necessitated a myringoplasty on the
      other (only hearing) ear. He is now happily rehabilitated with a dry but deaf
      left ear and a normally hearing right ear.

PMID- 23120551
TI  - Complete resolution of stage IIIB juvenile nasopharyngeal angiofibroma with
      radiation therapy.
AB  - Juvenile nasopharyngeal angiofibroma is a benign, locally aggressive, vascular
      tumour of adolescent males. Extension to intracranial cavity is not uncommon and
      presents difficulties in management. Here we report a patient who had Radkowsky
      stage IIIB lesion, with blood supply from internal carotid artery. In view of
      anticipated problems with surgery, the patient was treated with 30 Gy in 15#
      external beam radiotherapy. On follow up, tumour was noted to disappear gradually
      overtime and at 3 years complete disappearance was noted with normal return of
      vision. Hence we are re-affirming the earlier studies than angiofibroma mass
      regresses gradually after completion of radiotherapy. Radiotherapy is a useful
      way of treating angiofibroma with significant intracranial extension.

PMID- 23120552
TI  - Bronchial cast: a case report.
AB  - We present a case of a child who presented with respiratory distress mimicking
      foreign body aspiration which was treated by bronchoscopic extraction of
      bronchial cast. Early interventional bronchoscopy in management of plastic
      bronchitis, though difficult, provides an immediate benefit and good prognosis
      especially in patients with no underlying cardiopulmonary morbidity.

PMID- 23120553
TI  - Metachronous bilateral mucoepidermoid carcinoma of the parotid gland.
AB  - We report a very rare case of bilateral muco-epidermoid carcinoma of the parotid
      gland that underwent bilateral parotidectomy with neck dissections and
      radiotherapy. This case has done well for three years and suggests that
      metachronous bilateral mucoepidermoid carcinoma of the parotid gland, if treated
      as per the merits of each side, has a reasonable survival.

PMID- 23120554
TI  - Giant tumour of the pterygopalatine fossa.
AB  - Neurilemmomas are benign and slow growing tumours. Neurilemmomas of the
      pterygopalatine fossa are rare. In this paper we present a case of schwannoma
      arising in the pterygopalatine fossa with extension into infratemporal fossa and
      floor of the orbit. A transantral approach was used for excision of the tumor
      following which the defect in the floor of the orbit was reconstructed with the
      help of a temporoparietal flap.

PMID- 23120555
TI  - Parapharyngeal and retropharyngeal space abscess: an unusual complication of
      chronic suppurative otitis media.
AB  - Parapharyngeal and retropharyngeal abscess as a complication of cholesteatoma is
      an uncommon entity. We present the unusual case of a 32-year-old man with chronic
      suppurative otitis media, presenting with parapharyngeal and retropharyngeal
      abscess. This was treated with incision and drainage of the abscess followed by
      modified radical mastoidectomy for chronic suppurative otitis media.

PMID- 23120556
TI  - Primary B cell lymphoma of paranasal sinuses: a diagnostic surprise.
AB  - Primary lymphomas of paranasal cavities are rather uncommon entities. They have a
      variable presentation from fulminant destructive manifestations to chronic
      indolent type of disease. Chronic indolent form may mimic invasive fungal
      sinusitis in its presentation. Unless high index of suspicion is held and
      appropriate histopathology sections are taken from specimen, its diagnosis can be
      deceitful. We here by report a case of primary lymphoma of the paranasal sinuses
      which was radiologically and clinically suspected to be a invasive fungal
      sinusitis and later was proven to be a B cell lymphoma. Clinical similarities
      between lymphoma and invasive fungal sinusitis along with management issues are
      discussed in this article.

PMID- 23120557
TI  - Chondrosarcoma premaxilla.
AB  - We present a very unique case of a premaxillary chondrosarcoma arising in a
      relatively 'younger' female with apparently much 'better' disease free 7-year
      survival. The literature has been reviewed and a meaningful discussion regarding
      diagnosis and treatment is highlighted.

PMID- 23120558
TI  - Tuberculosis of tonsil associated with pulmonary foci.
AB  - Tuberculosis of tonsil is one of the uncommon forms of extra pulmonary
      tuberculosis. We report a case of tuberculosis of tonsil associated with
      pulmonary foci. A 48-year-old male presented with history of severe left sided
      throat pain of 10-15 days duration and fever of moderate degree of 7 days
      duration. Clinical diagnosis of left peritonsillitis was made. As the symptoms
      did not subside with antibiotics and analgesics malignancy was suspected, biopsy
      was done under local anesthesia and sent for histopathology. Histopathology
      revealed tuberculosis. He was evaluated further and primary foci was found in
      lung. The possibility of tuberculosis should be considered in a case with
      unilateral severe throat pain with congested tonsil not responding to usual line
      of treatment.

PMID- 23120559
TI  - Middle turbinate osteoma.
AB  - A 14-year-old female patient presented with six months history of progressive
      nasal obstruction on the left side associated with ipsilateral facial pain.
      Radiograph of the nose and paranasal sinuses showed a bony mass arising from the
      left lateral nasal wall. Under general anesthesia left lateral nasal wall is
      approached through a modifi ed Lynch incision. A bony mass arising from the ant
      part of the middle turbinate was removed. Histopathological examination of the
      resected specimen showed picture of an osteoma. The postoperative course was
      uneventful.

PMID- 23120560
TI  - Nasal tip metastasis: an unusual site and mode of spread in anaplastic thyroid
      carcinoma.
AB  - Anaplastic thyroid carcinoma (ATC) is the most aggressive and lethal form of
      thyroid malignancy which is difficult to treat. At the time of diagnosis,
      majority of patients have distant metastases most commonly in lung, bone, and
      liver. However nasal tip metastasis is not reported in literature. Implantation
      of malignant cells on nasal tip is also unknown. We hereby report an interesting
      and unusual mechanism for nasal tip metastasis in a patient with ATC.

PMID- 23120561
TI  - Sphenochoanal polyp - a rare diagnosis in nasal obstruction.
AB  - One of the most common nasal pathologies to present to an otolaryngologist is
      polyposis. Two well-recognized forms occur, the common antrochoanal polyp and the
      rare sphenochoanal polyp. Differentiation between the two is necessary for proper
      management by endoscopic sinus surgery.

PMID- 23120562
TI  - Sinonasal schwannoma with secondary changes.
AB  - Schwannomas of the Sinonasal tract are very rare, representing less than 4% of
      schwannomas arising in the head and neck [1]. The most frequent site is the
      acoustic nerve; other locations include the scalp, oral cavity, pharynx, larynx,
      trachea, parotid gland, and middle ear. Secondary changes in a Schwannoma are a
      very rare entity. We report a case of Sinonasal schwannoma with pseudoangiomatous
      changes. The purpose of this article is to highlight the possibility of unusual
      presentation of a sinonasal schwannoma.

PMID- 23120563
TI  - A giant tonsillolith.
AB  - Tonsilloliths or calculi of the tonsil are calcifications that form in the crypts
      of the palatine tonsil or around it. Small concretions are asymptomatic while
      large calcifications produce symptoms such as odynophygia, dysphagia and referred
      otalgia. We describe a case of a 24 years old female who presented with a six
      month history of mild throat discomfort and was found to have a large (3.1 * 2.7
      * 2.1 cm) calculus in her left tonsil for which a tonsillectomy was done. This is
      one of the largest reported cases in the world. The authors stress that symptoms
      of tonsillolith are unrelated to its size. The pertinent literature has been
      reviewed.

PMID- 23120564
TI  - Laryngocele - a case report and review of literature.
AB  - This is case report of 35-year old male patient presented with hoarseness and
      swelling on left side of neck. The swelling was noticed by the patient for 8
      months. It has been diagnosed clinically and radiologically as a combined
      laryngocele. The laryngocele has been successfully excised using and combined
      approach i.e., external and endoscopic methods. This case has been reported for
      its rarity at this age.

PMID- 23120565
TI  - Chondrosarcoma of nose and paranasal sinus - a rare presentation.
AB  - Chondrosarcoma, the most malignant cartilageneous tumor, constitute only 4% of
      non-epithelial tumours of the nasal cavity, paranasal sinuses and nasopharynx,
      making it one of the rarest malignancies. Here we present a case of Grade 1
      chondrosarcoma involving nose, maxillary sinus, ethmoids and sphenoid sinus
      managed surgically by wide excision. 12 months follow-up reveled no recurrence or
      complication.

PMID- 23120566
TI  - Multiple submandibular duct (wharton's duct) calculi of unusual size and shape.
AB  - Salivary gland stones are most common in the ductal system of submandibular
      glands and are calcified. A rare case of multiple submandibular duct (Wharton's
      duct) calculi of unusual size and shape in a 42 year old male patient, who
      presented with pain and swelling in the region of submandibular gland and hence
      reported. Sometimes a stone comes out into the mouth on its own or with gentle
      probing. However in this case a small intra-oral procedure is needed to remove
      the stone.

PMID- 23120567
TI  - Neurofibroma of the external ear - a case report.
AB  - Neurofibromas are relatively common tumours of the nervous system, but only a few
      cases involving the external ear have been reported. We are reporting here a case
      of a 20-year-old female with neurofibroma of the external ear. The primary
      complaint was cosmetic deformity. There was partial occlusion of the external
      auditory canal. The swelling was excised by postauricular approach. Surgery
      resulted in an excellent functional and cosmetic outcome.

PMID- 23120568
TI  - Tracheostomy in critically ill patients.
AB  - ENT surgeons are called in more often these days to perform tracheostomy in
      critically ill patients. When to perform tracheostomy is a question, which is
      most often asked. There are definite advantages for performing tracheostomy at an
      early stage of intensive care, but at the same time we need to be aware of the
      possible complications that are associated with it. Tracheal stenosis being one
      of the most common complications, which can be prevented if proper care is taken
      from the time tracheostomy is done.

PMID- 23120569
TI  - A comparative study of endoscope assisted myringoplasty and micrsoscope assisted
      myringoplasty.
AB  - OBJECTIVE: To determine the advantages and disadvantages of the endoscope as
      compared to the microscope in myringoplasty surgery and to compare the results of
      both groups. METHODS: Between January 2003 and September 2006, 100 patients
      underwent myringoplasty, 50 were endoscope assisted and 50 were microscope
      assisted. Results of surgery were compared at the end of six months post
      operation. RESULTS: In the endopscope group 82% of patients had a successful
      outcome and in the microscope group 86% of patients had a successful outcome.
      CONCLUSION: In myringoplasty surgery the endoscope has several advantages and a
      few disadvantages. The surgical outcome of endoscope assisted myringoplasty was
      comparable to the conventional microscope assisted myringoplasty, but in terms of
      cosmesis and post operative recovery patients in the endoscope group had better
      results.

PMID- 23120570
TI  - Laryngoceles - presentations and management.
AB  - INTRODUCTION: Laryngoceles usually present as cervical masses with or without
      hoarseness of voice. They are mostly unilateral and may be symptomatic or
      asymptomatic. They are classified as internal, external or combined. They have
      been described to be an occupational hazard among wind instrument players or
      glass blowers. They also occur in association with neoplasms of the larynx.
      MATERIALS AND METHODS: Here we report five patients with laryngoceles of whom two
      had bilateral laryngoceles, which are very rare. One patient had associated
      laryngeal malignancy for which total laryngectomy was performed. Two cases
      underwent excision via cervical approach. The rest were managed conservatively.
      CONCLUSION: Symptomatic cases have to be managed surgically while asymptomatic
      ones may be managed conservatively.

PMID- 23120571
TI  - Histological study of routine tonsillectomy specimen.
AB  - INTRODUCTION: Palatine and nasopharyngeal tonsils are lymphatic flesh clusters of
      tissue of the respiratory and digestive tract's epithelium. There is not much
      literature pertaining to the histological assessment of resected tonsils though
      anecdotal case reports of choristoma, squamous cell cysts of the tonsil have been
      reported which mimicked chronic tonsillitis. Tonsils also are an important site
      for head and neck cancer in adults.  AIM #ENTITYSTARTX00026; OBJECTIVE: To study
      the histological features of routine tonsillectomy specimens and to study for the
      presence of choristomatic tissue or any other benign pathology as a cause of
      chronic tonsillitis.  PATIENTS #ENTITYSTARTX00026; METHODS: Fifty consecutive
      tonsillectomy specimens, which were received in the department of Pathology,
      Gandhi Medical College, were evaluated with regards to clinical information.
      Among 50 patients, a slight predominance of men (56 %) over women (44 %) was
      observed. CONCLUSION: The mesenchymal tissue consisted mainly of epithelium and
      lymphoid tissue with cartilage in a single case and fat in three cases. The role
      of imaging techniques, in assessing the need for early surgical intervention in
      cases with chronic tonsillitis, can be determined by assessing the micropathology
      of tonsillectomy specimens and is an arena for further research. We discussed the
      role of FDG-PET scan in the assessment of the same.

PMID- 23120572
TI  - Anaesthesia for direct laryngoscopy with propofol and fentanyl or sufentanil.
AB  - AIM #ENTITYSTARTX00026; OBJECTIVE: To find if direct laryngoscopy (DL) could be
      done without using succinylcholine and secondly, to acertain the appropriate
      anesthetic regimen. PATIENTS AND METHODS: In a double blind placebo controlled
      study 67 patients aged 40-75 years of age, of both sex requiring direct
      laryngoscopy (DL) either for diagnosis or for biopsy were enrolled. The patients
      were randomly divided in three groups. The patients in group F and S received
      Fentanyl or Sufentanil respectively along with Propofol, whereas those in group N
      received normal saline (placebo) and propofol. The conditions of laryngoscopy,
      hemodynamic parameters and any adverse events were recorded. Good or fair
      conditions for laryngoscopy were achieved in 91% (21), 87% (19) and 73% (16) of
      patients in groups F, S and N respectively (p < 0.05) in favor of group F and S.
      During DL arterial pressure and pulse rate changes were minimal when propofol was
      administered along with opioids, (group F and S) compared to group N where only
      propofol was used. RESULTS: No serious side effects were seen in the three
      groups. Hence by these findings we concluded that better conditions of DL are
      achieved during anesthesia with propofol and fentanyl and sufentanil alone. The
      opioids provided additional benefit of stable hemodynamics.

PMID- 23120573
TI  - Modified intact canal wall mastoidectomy - long term results in hearing and
      healing.
AB  - INTRODUCTION: The classic intact canal wall (ICW) mastoidectomy with
      tympanoplasty (combined approach tympanoplasty) [1, 2] has anatomic constraints
      for clearance of disease from the anterior attic and sinus tympani leading to
      high recidivism. Farrior [3, 4] described the modification of this technique and
      senior author (AM) has been using it with further modifications since 1973.
      MATERIALS AND METHODS: We report our long-term experience in hearing and healing
      in 126 cases with special reference to the age (pediatric versus adults), ossicle
      status (presence or absence of stapes suprastructure) and type of cholesteatoma
      (Attic versus posterior-superior versus secondary acquired cholesteatoma).
      RESULTS: All the patients had unsafe CSOM and underwent Modified ICW
      mastoidectomy with primary ossiculoplasty except five where the procedure was
      staged. CONCLUSION: Modified ICW technique is a one-stage procedure with the
      lowest recidivism rate when compared to various other ICW techniques. There is no
      significant difference in relation to age of the patient or type of cholesteatoma
      if the operative cases are selected judicially.

PMID- 23120574
TI  - Bomb blast injury: effect on middle and inner ear.
AB  - OBJECTIVE: To study the symptomatology, clinical findings and the effects of
      blast injury on middle and inner ear in survivors of bomb blast. Settings City of
      Mumbai, India. METHODS: The study group consisted of 52 patients exposed to the
      bomb blast that occurred on 25th August 2003. RESULT AND ANALYSIS: The distance
      of the victim from the blast site has no major infiuence in producing effects on
      middle and inner ear in our study of the surviving individuals. Rupture of the
      tympanic membrane occurs due to the positive wave but both everted and inverted
      edges can be found in multiple perforations of the tympanic membrane.

PMID- 23120575
TI  - Tubercular laryngitis: case series.
AB  - INTRODUCTION: Tubercular laryngitis is a known entity since a long time but it's
      presentation, diagnosis and management has undergone a drastic makeover after the
      advent of chemotherapy in the form of ATT (Anti tubercular treatment), modernized
      diagnostic aids and early detection of lesions. MATERIALS AND METHODS: This
      prospective study was conducted on 180 patients. Each patient were subjected to
      detailed history and thorough ENT and head neck examination including laryngeal
      examination by visualization of the vocal cords, possibly using indirect
      laryngoscopy,. exible naso-laryngoscopy or rigid laryngoscopy Results Tubercular
      laryngitis was clinically diagnosed by laryngeal endoscopy and diagnosis con.
      rmed by laryngeal biopsy. CONCLUSION: All patients showed remarkable improvement
      with anti-tubercular treatment.

PMID- 23120576
TI  - Endonasal dacryocystorhinostomy: a prospective study.
AB  - OBJECTIVE: The objectives of this study are to report the results of Endonasal
      Dacryocystorhinostomy (EnDCR) and the role of silicon intubation in EnDCR in
      Indian population. STUDY DESIGN: The authors conducted a prospective case series.
      METHODS: 290 patients underwent EnDCR between January 2002 and July 2007 - 240
      cases without silicon intubation and 50 cases with silicon intubation. Patients
      were followed up for an average of 18.6 months in first group and 5.2 months in
      second group. Outcome was evaluated subjectively and objectively. RESULTS: In
      EnDCR without silicon intubation, the procedure was successful in 93.3% of cases.
      In EnDCR with silicon intubation, the procedure was successful in 96% of cases.
      CONCLUSION: EnDCR is a safe procedure with good success rate and has potential
      advantages in chronic dacryocystitis cases. The use of silicon intubation in
      nasolacrimal pathway helps in maintaining the patency of rhinostomy.

PMID- 23120577
TI  - Comparative study of hearing improvement in type 1 tympanoplasty with and without
      canalplasty.
AB  - INTRODUCTION: Widening of the external auditory canal is canalplasty. It is an
      intergral part of tympanoplasty, especially in anterior perforations and gives
      wide surgical access for proper repair. MATERIALS AND METHODS: After elevating
      tympanomeatal flaps the canal is widened using conical cutting and diamond burrs
      following which entire tympanic annulus is visible and corresponds to an inverted
      truncated cone. RESULTS: Canalplasty gives 9 db gain in hearing compared to
      without canalplasty. CONCLUSION: Canalplasty gives better visualization, better
      graft placement and better post-operative care.

PMID- 23120578
TI  - Surgical management of parapharyngeal tumors - our experience.
AB  - Fifteen cases of parapharyngeal tumors treated surgically in ENT department of
      Calcutta National Medical College in last 2 years were included, 80% cases were
      of benign tumors, most common being schwannomas. Most important investigation was
      found to be CT scan. The study gives an overview regarding the surgical approach,
      based upon the extent and histology of the tumor and transcervical approach was
      found to be most efficient for all practical purpose.

PMID- 23120579
TI  - Deep-neck space infections - a diagnostic dilemma!
AB  - Deep Neck Space Infections (DNI) are a potentially life threatening condition.
      This paper highlights the importance of their early diagnosis and early
      intervention. The deep-neck space infections may be odontogenic in origin. The
      severe airway compromise caused by them may make diagnosis difficult. Suspicion
      of simultaneous occurrence of tetanus and retropharyngeal space infection in a
      child can further increase the dilemma.

PMID- 23120580
TI  - Kimura's disease: an unusual case of neck mass.
AB  - Kimura's disease usually affects young men of Asian descent and is characterized
      by swelling in the region of head and neck. A case of Kimura's disease is
      reported who presented with neck mass. Fine needle aspiration cytology was
      doubtful of lymphoma. Histopathological examination of excised specimen was
      reported as Kimura's disease.

PMID- 23120581
TI  - Post traumatic psuedoaneurysm of the lingual artery.
AB  - Post traumatic pseudoaneurysm is a well documented complication of vascular
      injuries which needs early diagnosis and early management otherwise there may be
      significant morbidity and mortality. We present a patient who had been operated
      elsewhere for a foreign body lodged in neck during splinter injury sustained
      while bursting a cracker. He presented to ENT department of our hospital with
      bleeding from the wound site. We are reporting this case because pseudoaneurysm
      of the lingual artery as such is very rare. We could not find any other reported
      case in available English literature. Moreover the treating ENT surgeons need to
      be sensitized to the presence of such an entity and hence avoid late
      complications.

PMID- 23120582
TI  - Mucormycosis of nose and paranasal sinuses with orbital complication in young
      diabetic.
AB  - A case report of mucormycosis of nose and paranasal sinuses with sudden loss of
      vision in a young diabetic with good recovery after endoscopic debridement,
      systemic and topical amphotericin B and control of Diabetes mellitus.

PMID- 23120583
TI  - Varied manifestations of Rosai-Dorfman disease and its management - a case report
      and review of literature.
AB  - Rosai Dorfman disease or sinus histiocytosis is a rare, idiopathic, benign and
      self-limiting histiocytic proliferative disorder, usually seen in younger
      patients. It most commonly involves the cervical lymph nodes, with a predominant
      infiltration of sinusoidal histiocytes and classically presents with massive
      cervical lymhadenopathy. Extranodal disease occurs in about 43% of cases and
      produces different signs and symptoms depending upon its location. We report a
      case of this disorder in 22-year-old male with initial isolated involvement of
      bilateral nasal cavity and paranasal sinuses with subsequent involvement of
      cervical lymph nodes and skin. The clinical presentation, histologic
      characterstics, radiographic findings and treatment of the disease are discussed.

PMID- 23120584
TI  - Cutaneous matastasis from sino-nasal malignant melanoma - a rare case report.
AB  - To report a case of disseminated cutaneous metastasis from malignant melanoma of
      sino-nasal region. A 53-year-old man from rural parts of West Bengal presented
      with progressive nasal obstruction. CT scanning was done to know the extent of
      the mass and punch biopsy from the mass was performed. Malignant melanoma of sino
      nasal region was diagnosed and chemotherapy was started. The patient developed
      cutaneous deposits after two cycles of chemotherapy. The patient developed
      cutaneous deposits during the course of chemotherapy. Excision biopsy from
      cutaneous deposits revealed malignant melanoma. A rare case of diffuse cutaneous
      metastasis of malignant melanoma is presented here along with review of
      literature.

PMID- 23120585
TI  - Lupus vulgaris of external nose.
AB  - Lupus vulgaris is the commonest form of cutaneous tuberculosis which commonly
      involve trunk and buttocks. Lupus vulgaris affecting nose and face, are rarely
      reported in India. This study reports an unusual case of lupus vulgaris involving
      the external nose that showed dramatic outcome after six months of anti-
      tubercular treatment.

PMID- 23120586
TI  - Chondrosarcoma of the arytenoids- a rare laryngeal malignancy.
AB  - Even though laryngeal malignancies are the most frequent primary malignancies of
      the upper aero digestive tract except for oral cavity cancers, laryngeal
      chondrosarcomas are rare tumors, constituting less than 1% of all laryngeal
      tumors. We present a rare case of chondrosarcoma arising from the right arytenoid
      cartilage with sub glottic extension. The mode of presentation and management of
      the case is presented along with a review of the literature.

PMID- 23120587
TI  - Prosthetic management of atrophic rhinitis.
AB  - Atrophic rhinitis is a form of chronic rhinitis in which the nasal mucosa
      atrophies and hardens, causing the nasal passages to dilate and dry out. Other
      prominent findings include bad smell, extensive nasal crusting and bleeding.
      Surgical and nonsurgical methods have been advocated for its treatment. We
      describe a prosthetic technique for its management.

PMID- 23120588
TI  - Adult chiari malformation presenting as bilateral vocal cord paralysis.
AB  - In the Chiari malformations, herniation of the cerebellar tonsils through the
      foramen magnum into the cervical spinal canal can often result in headaches and
      spinal cord deficits. Bilateral vocal cord paralysis has been reported as a
      result of Chiari malformation but is rare and the vast majority of reports have
      been in the paediatric population. We report a case in a 68-year-old man with
      adult Chiari malformation where aspiration pneumonia from bilateral vocal cord
      palsy was the only manifestation of this malformation.

PMID- 23120589
TI  - Hemifacial microsomia.
AB  - Hemifacial microsomia (HFM) is a craniofacial disorder characterized by a wide
      spectrum of anomalies, including conductive hearing loss due to external and
      middle ear deformities [1]. Hemifacial microsomia is the second most common
      developmental craniofacial anomaly after cleft lip and palate. Diagnostic imaging
      is important for presurgical evaluation of patients with this anomaly; however
      the broad spectrum of abnormalies encountered in patients with hemifacial
      microsomia can be confusing [2]. We present a case of a hemifacial microsomia in
      12 year old male.

PMID- 23120590
TI  - Delusional parasitosis in ENT.
AB  - Otolaryngologists in India often encounter patients with various insects
      presenting as foreign bodies in the ear and nose. However they overlook the
      possibility of the clinical entity that has come to be known as delusional
      parasitosis. Three patients presented in our OPD with this condition and their
      case reports are discussed.

PMID- 23120591
TI  - Pneumocephalus presenting as a complication of chronic otitis media - a case
      report.
AB  - Pneumocephalus secondary to chronic otitis media is an extremely rare phenomenon.
      Despite its rarity, the sequelae of intracranial air associated with otitis media
      may be grave if misdiagnosed. In this report a case of pneumocephalus following
      chronic mastoid infection is presented and the possible mechanism, diagnostic
      measures and the management is discussed.

PMID- 23120592
TI  - Oxymetazoline plus dexpanthenol in nasal congestion.
AB  - AIMS: To compare the efficacy and tolerability of Oxymetazoline 0.05 % plus
      Dexpanthanol 5% versus Xylometazoline 0.1 % nasal drops in patients with nasal
      congestion due to allergic rhinitis and following nasal surgery. METHODS: An
      investigator-blind, randomized, controlled, phase IV clinical trial conducted in
      100 patients with acute allergic rhinitis or patients post-nasal surgery.
      Patients received either Oxymetazoline 0.05% with Dexpanthanol 5% (OD) or
      Xylometazoline 0.1% (XO) nasal drops. RESULTS: Relief from nasal congestion was
      significantly better in the OD group then in the XO group (mean nasal scores 1.24
      vs 1.86). Significantly more improvement in sneezing and decrease in nasal
      discharge was seen in the OD group than the XO group. Nasal irritation in the OD
      group was significantly less as compared to XO group (0.38 v/s 1.12 on second day
      and 0.10 vs 0.36 on the fourth day). The recovery time for OD group was 1.08
      hours, which was significantly (46 min) lesser than that of the XO group. Rebound
      congestion was significantly less in OD as compared to XO group (6.25% vs
      82.98%). 93.75% of the physicians in the OD group and 51.28% in XO group reported
      response to therapy as good to excellent. 95.83% patients in the OD group and
      only 52.91% patients in the XO group rated tolerability to therapy as good to
      excellent. CONCLUSION: Oxymetazoline and dexpanthenol combination has a better
      efficacy, shorter recovery time, causes lesser rebound congestion and has better
      tolerability than xylometazoline.

PMID- 23120593
TI  - Laryngeal fiberscopic surgery - an alternate approach to microlaryngeal surgery.
AB  - Microlaryngeal surgery (MLS) is difficult in patients with anaesthetic and
      cervical contraindications. An alternative approach is proposed here using a
      flexible laryngeal fiberscope and specially designed laryngeal instruments under
      local anaesthesia. Equipment and technique of the procedure is described.
      Indications and contraindications are highlighted based on our experience of 117
      patients. Laryngeal fibrescopic surgery (LFS) was found to be a safer
      alternative. But this procedure cannot be used for all laryngeal pathologies.

PMID- 23120594
TI  - The study of co-morbid conditions in adults with allergic rhinitis, from Mumbai,
      Maharashtra, India and their comparison with children.
AB  - Allergic rhinitis (AR) is an allergen-induced inflammation of the nasal mucosa.
      Several studies have shown a link not only between AR and asthma but also with
      other co-morbid conditions. It is important to recognize the onset and existence
      of these co-morbid conditions, for adequate treatment, prevention of the
      development of new allergen sensitizations and air-way hypersensitivities. This
      is a prospective study of co-morbid conditions in adults with AR, from Mumbai,
      Maharashtra, India and compares them with those in children 23 consecutive
      children below 6 years (Group 1), 42 children between age of 6 years and 14 years
      in Group 2 and 57 adults in Group 3 were selected for the symptoms of AR
      (sneezing, watering and blocked nose), which were currently sufficiently
      troublesome to require medication. A high association of co-morbid conditions
      with AR was found. More than 80% suffered from one to three co-morbid conditions
      each. The most common co-morbid condition was asthma in all the groups. Often
      asthma and sinusitis was asymptomatic and a high degree of suspicion was needed
      for diagnosis. Adults had the highest prevalence of sinusitis and allergic
      conjunctivitis. Prevalence of urticaria was similar in children as well as
      adults. Studies with larger data samples are needed to confirm these
      associations.

PMID- 23120595
TI  - Use of autogenic and allogenic malleus in tympanic membrane to footplate assembly
      - long-term results.
AB  - The objective of this study was to assess the functional performance and long
      term stability of autogenic and allogenic malleus used for ossiculoplasty as
      tympanic membrane to footplate assembly. A retrospective study of 119 patients
      who underwent such ossiculoplasty in closed cavity mastoidectomy from 1989-2004
      was carried out. There was no extrusion in any of our cases. Serviceable hearing
      (<20 dB air bone gap closure) was achieved in 24 out of 37 (65%) over long-term
      follow up of more than 1 year (mean and median for follow up being 37.4 and 30
      months respectively). Thus malleus ossicle graft give acceptable long-term
      hearing results in one of the most difficult ossiculoplasty situations (absence
      of stapes suprastructure and malleus) with virtually no extrusion problems.

PMID- 23120596
TI  - Endoscopic repair of cerebrospinal fluid rhinorrhea - Manipal experience.
AB  - Otolaryngologists play a major role in the management of cerebrospinal fluid
      (CSF) rhinorrhea. A thorough understanding of the underlying pathophysiology and
      the various treatment options available is essential to achieve the best possible
      results.In this paper, we are highlighting the pathophysiology, diagnosis and
      surgical technique involved in the repair of cerebrospinal fluid rhinorrhea. A
      retrospective study conducted in the department of ENT and Head and Neck Surgery,
      Kasturba Hospital, Manipal is presented to highlight our experience with
      cerebrospinal fluid rhinorrhea.Eleven patients were managed in the department of
      otolaryngology between 1999 and 2005. Seven had spontaneous CSF rhinorrhea, three
      were due to trauma and one iatrogenic, following surgery. Commonest anatomic site
      of leak was the cribriform plate in 4 cases. Other sites included sphenoid [2],
      lateral lamella [2], fovea ethmoidalis [2] and olfactory groove [1]. Onlay
      technique was performed in 10 out of 11 patients. Closure was successful in 10
      out of 11 cases in the first attempt. One patient underwent revision surgery.
      Patients were followed up for a period ranging from 3 months to 3 years.CSF
      rhinorrhea is a potentially fatal condition which requires precise and urgent
      treatment. The transnasal endoscopic repair of CSF leak has a high success rate
      with low morbidity when performed by experienced endoscopic sinus surgeons. Our
      experience in managing this condition is presented.

PMID- 23120597
TI  - Assessment of deafmute patients: a study of ten years.
AB  - Present prospective study was conducted on 350 patients presenting with chief
      complaints of impaired hearing and delayed speech from 1996-2006. The aim of the
      present study was to find out the prevalence of deafmutism in our area, the
      aetiology of childhood deafness and to ascertain the role of acoustic reflex test
      (ART) for hearing screening considering brain stem evoked response audiometry
      (BSERA) as gold standard. A detailed history, clinical and other relevant
      systemic examination and investigations were done to find out the cause. All
      patients were subjected to ART test and BSERA. Male to female ratio was 2.1:1.
      Prevalence was found to be 5.59 per one lac population in our district. The
      commonest age of presentation was in the second decade. The causes for childhood
      deafness were genetic (15.8%), embryopathies (10%), perinatal (10.8%) and
      postnatal problems (12.5%). In 50.6% cases it was aediopathic. Congenital
      syndromic abnormalities were found in 5.4% patients. In BSERA 21% patients were
      found to have residual hearing varying from 60 dB to 100dB. The positive
      predictive value of ART was found to be low (10.4%). Hence it was recommended
      that ART should not be used as screening tool for childhood deafness.

PMID- 23120598
TI  - Neonatal screening for hearing loss: pilot study from a tertiary care centre.
AB  - Many developed countries have well established universal neonatal hearing
      screening programs. In India, the viability of such a program, in an already
      overburdened health system is indeed a challenge. This cross sectional study was
      undertaken to evaluate the possible burden of hearing loss among neonates born at
      a tertiary care hospital in Southern India. Five hundred neonates were screened
      with automated distortion product otoacoustic emission (aDPOAE) for hearing loss,
      9.2% of whom had one or more high risk factors. Although 6.4% had hearing loss at
      initial assessment, only 1.6% had hearing loss on retesting with aDPOAE.
      Retesting with OAE before an automated Auditory brainstem response (aABR) helped
      to exclude patients without hearing loss. The frequency of moderate to moderately
      severe hearing loss in this study was 0.6%. This pilot study underscores the
      importance of the introduction of screening for congenital deafness in
      specialized centers in India, despite its challenges.

PMID- 23120599
TI  - Comparative evaluation of endoscopic with conventional septoplasty.
AB  - A study was conducted to assess the merits and demerits of endoscopic
      septoplasty. Fifty patients having symptomatic DNS were randomly divided into two
      groups of 25 patients each. One group underwent endoscopic septoplasty and other
      group underwent conventional septoplasty. The groups were compared regarding the
      complaints with pack in postoperative period, relief of symptoms after surgery
      and complications. The symptoms complained by the patients with pack in
      postoperative period and complications after surgery were significantly less in
      endoscopic septoplasty group.

PMID- 23120600
TI  - Distortion product otoacoustic emissions: comparison of sequential vs.
      simultaneous presentation of primary tones.
AB  - Distortion product otoacoustic emissions are one form of evoked otoacoustic
      emissions. DPOAEs provide the frequency specific information about the hearing
      status in mid and high frequency regions. But in most screening protocols TEOAEs
      are preferred as it requires less time compared to DPOAE. This is because, in
      DPOAE each stimulus is presented one after the other and responses are analyzed.
      Grason and Stadler Incorporation 60 (GSI-60) offer simultaneous presentation of
      four sets of primary tones at a time and checks for the DPOAE. In this mode of
      presentation, all the pairs are presented at a time and following that response
      is extracted separately whereas, in sequential mode primaries are presented in
      orderly fashion one after the other. In this article simultaneous and sequential
      protocols were used to compare the Distortion product otoacoustic emission
      amplitude, noise floor and administration time in individuals with normal hearing
      and mild sensori-neural (SN) hearing loss. In simultaneous protocols four sets of
      primary tones (i.e. 8 tones) were presented together whereas, in sequential
      presentation mode one set of primary tones was presented each time. Simultaneous
      protocol was completed in less than half the time required for the completion of
      sequential protocol. Two techniques yielded similar results at frequencies above
      1000 Hz only in normal hearing group. In SN hearing loss group simultaneous
      presentation yielded signifi cantly higher noise floors and distortion product
      amplitudes. This result challenges the use of simultaneous presentation technique
      in neonatal hearing screening programmes and on other pathologies. This
      discrepancy between two protocols may be due to some changes in biomechanical
      process in the cochlear and/or due to higher distortion/noise produced by the
      system during the simultaneous presentation mode.

PMID- 23120601
TI  - Role of magill forcep in retrieval of foreign body coin.
AB  - Children swallow coins more than any other object. Many methods for removal of
      impacted coins at the upper end of the oesophagus are enumerated in literature,
      each having it's own merits and demerits. This retrospective study in 100
      consecutive paediatric patients presents a magill forcep technique for removal of
      coins under inhalational anaesthesia using Mc-Intosch laryngoscope. Intubation
      and rigid endoscopy both were avoided, thereby minimizing hospital stay and cost
      of treatment. This also decreases the chances of complications. Moreover the
      technique was found to be at par with rigid endoscopy in term of efficacy and
      safety. However interestingly statistical analyses of the data by 'Chi
      SquareTest' (xi(2)) revealed the technique to be more applicable in younger age
      group i.e. 0-6 years.

PMID- 23120602
TI  - Study of intratemporal course of facial nerve and its variations - 25 temporal
      bones dissection.
AB  - INTRODUCTION: Facial nerve is the longest nerve in a bony canal. Three
      dimensional anatomical knowledge provides the foundation for safe and skillful
      dissection of the very complex temporal bone and tortuous facial nerve.
      OBJECTIVE: A small surgical area and a fair incidence of anatomical variations
      makes the facial nerve prone to injury. Inspite of the problems presented, the
      nerve serves as an excellent landmark and guide to the competent otological
      surgeon who studies it deligently, the neophyte on the other hand lives in
      constant fear of finding the nerve inadvertently. The present study was
      undertaken to explore the microanatomy of tympano-mastoid segment of facial
      nerve. MATERIALS AND METHODS: The current study was conducted at Dept of E.N.T,
      temporal bone lab, J.N.M.C Sawangi, Wardha. 25 temporal bones were dissected to
      study the various parameters of the tympano-mastoid segments of the facial nerve,
      its relations with the important middle ear structures and their anomalies.
      RESULTS: Mean length of tympanic segment was 9.28mm and that of the mastoid
      segment was 13.7mm. Mean depth of second genu from the cortex was 19.72mm.
      Amongst the variations noted commonest were the variations in the tympanic
      segment of about 12 %. An overhang in the region of oval window and a hump at the
      second genu was noted in one specimen each. CONCLUSION: The variations in the
      tympanomastoid segment occur with sufficient frequency showing not much racial
      and geographical variance.

PMID- 23120603
TI  - Small cell neuroendocrine carcinoma of nose and paranasal sinuses: a study of
      three cases with short review of the literature.
AB  - Primary small cell neuroendocrine carcinoma (SNEC) of nose and paranasal sinuses
      is an extremely rare malignant tumour known for its aggressive clinical course,
      high rate of recurrence and poor prognosis. Only 69 cases have been reported in
      world literature till March, 2006. This tumour usually occurs in elderly persons
      with main complaints being nasal obstruction, epistaxis, loss of visual acuity,
      exophthalmos, local pain and rarely tender swelling over the sinuses.
      Computerized tomography scan (CT) is essential to assess the size, extent of the
      tumour, evidence of bone destruction and infiltration to orbit and brain. Due to
      its rarity, the understanding of pathogenesis of the disease, diagnosis and ideal
      treatment have been difficult. The origin of the tumour is believed from basal
      cells of the olfactory mucosa. The present study deals with three cases of SNECs
      of nose and paranasal sinuses in elderly males, their clinical presentations, CT
      scan findings, histopathological diagnosis with short review of literature.

PMID- 23120604
TI  - Evaluation of auditory brainstem responses for hearing screening of high-risk
      infants.
AB  - Auditory brainstem responses (ABR) were recorded in 30 normal and 60 high-risk
      neonates with gestational age between 30 and 45 weeks. The normative data of
      normal group as regard to age, sex and various parameters of ABR were compared
      with high-risk group. ABR parameters especially wave V and interwave V-I
      intervals were significantly prolonged in high-risk infants. An infant was
      considered to "pass" the ABR test if an identifiable and replicable wave V
      response was present at 30 dB HL in both ears. All the normal neonates had click
      thresholds consistent with normal hearing. 12 of the highrisk neonates showed
      mild to moderate hearing impairment (absent replicable wave V at 30-60 dB HL) and
      2 of them showed severe to profound hearing impairment (absent replicable wave V
      at 70 dB HL). 9 of the "failed" group were reevaluated within 3 months and
      several times thereafter if the abnormal responses persisted. 2 (3.3%) infants
      showed persistent hearing loss, which was confirmed later by behavioral
      audiometry.

PMID- 23120605
TI  - Home auditory training program (HAP) for cochlear implantees and hearing impaired
      children using hearing aids-an outcome of a three-year research project.
AB  - INTRODUCTION: Use of cochlear implants has been a turning point in the life of
      the hearing-impaired children enabling them to participate in the world of
      sounds. Research shows that even after cochlear implantation auditory training is
      necessary as it facilitates the development of verbal skills. A number of kits
      for auditory training are available in the West. The author had an exposure to a
      number of auditory training kits in the US, as a part of her Fulbright Research
      Fellowship. In our country, there is a dearth of such material for auditory
      training. Besides this, India being a multilingual country, it becomes difficult
      if not impossible to develop language specific auditory programs. Hence, the need
      for the project proposal which was to develop material in Hindi and Marathi in
      the form of kit and CD-ROMs for the various levels of auditory training.
      METHODOLOGY: With the help of latest scientific techniques, material in the form
      of worksheets, audiocassettes and CD-ROMs were developed and field tested for all
      four levels of auditory training. Children with hearing impairment using hearing
      aids and cochlear implants were given auditory training using the developed
      material. RESULTS: t-test which was carried revealed that there is a significant
      difference between pre and post training performance of children. CONCLUSIONS: A
      systematic approach in the form of a kit comprising of audio cassettes and CD
      ROMs is now available in Hindi and Marathi for use at home for professionals and
      parents of children with hearing impairment.

PMID- 23120606
TI  - Evaluation of benefits of nasal septal surgery on nasal symptoms and general
      health.
AB  - OBJECTIVE: The purpose of the study was to analyze the patient's satisfaction
      following nasal septal surgery based on their subjective opinion and to study
      whether the SNOT-22 can be used as a reliable outcome measure for successful
      septal surgery. STUDY DESIGN: Between Oct 2005-July 2007, sixty consecutive adult
      patients who underwent nasal septal surgery and met the study criterion were
      enrolled. The patients were asked to fill in the SNOT-22 questionnaire both prior
      to and at regular follow up periods after the surgery. RESULTS: The mean total
      preoperative SNOT score (of all 22 items) was 20.67 and the mean total
      postoperative SNOT-22 score was 10.48 (t = 8.8135, p < 0.001 highly significant).
      On further analysis, improvement was seen in subcategories of Nasal Symptoms (t =
      8.0825, p < 0.001 highly significant), Non Nasal Symptoms (t = 3.0913, p < 0.0025
      significant), General health symptoms (t = 4.8602, p < 0.001 highly significant)
      and Nasal Obstruction (t = 7.7652, p < 0.001 highly significant). CONCLUSION: The
      SNOT-22 score is a useful and reliable tool in nasal septal surgery in that it
      combines both nasal specific and quality of life related questions, which can be
      assessed individually and together both pre and post operatively.

PMID- 23120608
TI  - Fourth branchial pouch sinus - an unusually late initial presentation.
AB  - OBJECTIVE: Here we present an unusual case of a male patient with 4th branchial
      pouch sinus with an initial presentation of pseudothyroiditis at an unusually
      late age of 20 years. METHOD: Case report and a review of the world literature
      concerning 4th branchial pouch sinus is presented. RESULT: The patient was
      diagnosed by radiology and endoscopy and treated surgically. Histopathology
      revealed chronic inflammatory changes, which pointed towards recurrent sub
      clinical low-grade inflammations over the years keeping the condition occult till
      20 years of age. CONCLUSION: According to available literature it almost always
      presents in the first decade of life when it might be misdiagnosed. However our
      report shows it may also exist with sub clinical inflammations or infections and
      present at a much later stage in life, when the possibility of such a sinus
      shouldn't be ruled out on the basis of lack of history of recurrent neck
      inflammations.

PMID- 23120607
TI  - Meningo-encephalocoele of temporal lobe-management by blind SAC closure.
AB  - Brain herniation into the middle ear and mastoid is rare but is a described
      complication of chronic ear disease. The diagnosis is mainly clinical and
      requires a high index of suspicion. This can be confirmed by imaging studies.
      Different surgical modalities have been described in managing this condition. We
      present a case managed by combined trans-mastoid mini-craniotomy approach and
      blind sac closure.

PMID- 23120609
TI  - Extraluminal hypopharyngeal foreign body.
AB  - Ingestion of a foreign body is a problem seen in nearly all otolaryngologic
      practices. Ingested foreign bodies which migrate extraluminally are rare
      occurrences. If untreated, they may result in life threatening complications. We
      are reporting a case of sharp metallic pin which migrated extraluminally in the
      hypopharynx and became lodged in the soft tissue. It was successfully removed by
      direct laryngoscopy.

PMID- 23120610
TI  - Zenker's diverticulum - a case report.
AB  - A Zenker's diverticulum is a blind pouch that branches off the cervical
      esophagus. Affected individuals may suffer from long-standing swallowing
      difficulties, regurgitation, bad breath, weight loss, and even aspiration.. Here
      we report a 80-years-old male presenting with dysphagia and regurgitation. Barium
      swallow reported the presence of a Zenker's diveticulum. In view of the patient's
      age, endoscopic diathermy was considered as a therapeutic option for the
      management.

PMID- 23120611
TI  - Papillary carcinoma in a supra hyoid thyroglossal duct cyst - an unusual
      presentation.
AB  - Carcinomatous transformation of ectopic thyroid elements within the thyroglossal
      tract is a rare entity. We report a case of primary papillary carcinoma of
      thyroid presenting within the thyroglossal duct cyst in a 23 year old gentleman.
      The patient presented to us, as a case of suprahyoid thyroglossal cyst with sub
      lingual involvement and he underwent surgical excision of the entire thyroglossal
      tract by Sistrunk's approach. The post-operative histopathological diagnosis was
      of a papillary carcinoma within the thyroglossal duct cyst. Hence, the patient
      was evaluated for a malignant focus in the thyroid which proved negative. He was
      counseled regarding the possibility of developing Carcinoma in the thyroid gland
      and offered two options of further management viz., total thyroidectomy followed
      by life long thyroid suppression or watchful observation and follow up. As the
      patient belonged to the low risk group, he opted for the second option. He is
      presently kept under meticulous follow up and remains asymptomatic till date. We
      present the pre- and post-operative imaging, intra-operative findings, histo
      pathological features and review the present world literature on this rare
      entity.

PMID- 23120612
TI  - Intranasal drug delivery: a novel approach.

PMID- 23120613
TI  - Psychological implications in ENT diseases.
AB  - We are sometimes faced with psychic derangement or overlay in some of the ENT
      diseases and the link between patient's psyche and any ENT disease at times
      becomes signifi cant and troublesome. The conditions in the fi eld between
      otorhinolaryngology and psychiatry can be classifi ed as psychiatric symptoms
      resulting from ENT diseases or interventions and those expressing themselves as
      ENT symptoms due to mental ailment. The former include hearing impairment,
      dizziness, tinnitus, choked airway, bad oral breath, stuffy nose, traumatic
      interventions and external nasal deformities. The later include exaggerated and
      diminished pharyngeal refl ex, globus hystericus, speech disorders, vasomotor
      rhinitis, nose picking, choked feeling, dizziness and headache. At times diseases
      originate in the human mind (consciousness), causing negative thoughts like
      jealousy, anger, and depression due to frustration. p ]A healthy mind in a
      healthy body generates sound and noble thoughts. Once a healthy body-mind
      relationship is established, we can be reasonably sure that greater happiness and
      success is within our reach. Patient seeking help from ENT surgeons to change
      their physical appearances and or function may not understand that the ultimate
      goal of surgery is to bring about psychological change by modifying the physical
      change, which is important aspect in septorhinoplastic surgery. At times patients
      asking for corrective rhinoplasty for minor external nasal deformities may have
      underlying psychological disturbance and use even slight external nasal deformity
      as scapegoat for psychological upset. Males are more diffi cult patients
      psychologically for any facial cosmetic surgery. These days some patients read
      about their diseases or treatment on the Internet and get more confused and
      psychologically disturbed due to rare causes of their illness, rare complications
      and diversity of treatment available.

PMID- 23120614
TI  - Balloon sinuplasty - the first Indian experience.
AB  - The surgical management of sinusitis was revolutionized worldwide with the advent
      of the rigid Hopkins rod nasal endoscopes three decades ago. The traditional
      Messerklinger technique, was thus propagated worldwide by Prof. Stammberger, from
      the University of Graz in Austria and has come into vogue as functional
      endoscopic sinus surgery (FESS). The principal aim behind this procedure was the
      maximal preservation of the nasal mucosal integrity, while providing optimal
      disease clearance. Today, the introduction of a new technological innovation
      called 'balloon sinuplasty', has taken the field of sinus surgery a step further.
      This new technology is very similar to the principles of balloon angioplasty and
      today, this system has added an efficient, non-invasive tool in the armamentarium
      of the innovative endoscopic rhinologist. This FDA approved technique, in recent
      times has provided excellent results in various centers across the western world.
      We share our first surgical experience with the introduction of this cutting-edge
      technology in India.

PMID- 23120615
TI  - Hearing loss among prison inmates in India - a pilot study.
AB  - AIMS: This study was done to assess the pattern of hearing loss and the types of
      ear diseases causing hearing loss among prisoners in an Indian prison. MATERIALS
      AND METHODS: A total of 102 inmates were studied by subjecting them to a complete
      ENT evaluation and pure tone audiometry. RESULTS: Seventy inmates had normal
      bilateral peripheral hearing sensitivity while 32 had some degree of hearing
      impairment. Almost 50% of the hearing loss among the inmates was found to be
      sensorineural. CONCLUSION: This study supports earlier reports of high incidence
      of hearing loss among prison inmates. The majority with sensorineural hearing
      loss were in the younger age group but since this study was not designed to
      determine the cause or risk factors, this cannot be commented upon. Infective ear
      diseases were found to be a significant etiological factor for conductive hearing
      loss.

PMID- 23120616
TI  - Audit in clinical practice.
AB  - BACKGROUND AND OBJECTIVES: Audit dates back to as early as 1750 BC when king
      Hammurabi of Babylon instigated audit for clinicians with regard to outcome.
      Clinical audit is a way of fi nding out whether we are doing what we should be
      doing. It also verifi es whether we are applying the best practice. METHODS: An
      audit cycle involves setting-up of standards, measuring current practice,
      comparing results with standards (criteria), changing practice and re-auditing to
      make sure practice has improved RESULTS AND INTERPRETATIONS: A 'clinical audit'
      is a quality improvement process that seeks to improve patient care and clinical
      outcomes through a systematic review of care against explicit criteria, and the
      implementation of change. Changes are implemented at an individual, team or
      service level and a subsequent re-audit is done to confi rm improvement in health
      care delivery. CONCLUSION: The importance of audit in healthcare sector needs to
      be appreciated by the relevant authorities. The most frequently cited barrier to
      successful audit is the failure of organizations to provide suffi cient fund and
      protected time for healthcare teams.

PMID- 23120617
TI  - Our experiences with parapharyngeal space tumors and systematic review of the
      literature.
AB  - OBJECTIVES: To find out the geographical distribution, age, sex, mode of
      presentation, diagnostic modalities, surgical approaches, postoperative
      complications, follow-up and histopathology of parapharyngeal space tumors (PFT)
      through world wide web search (WWWS) and PFT of our series. MATERIALS AND
      METHODS: A retrospective study of all PFT seen and treated in S.R.N Hospital,
      Allahabad between 1990 and 2006 was done. A systematic review of the literature
      was done through WWWS. RESULTS: PFT were commonest in the Asian zone. Incidence
      was highest in the 3rd and 4th decade. Oropharyngeal (100%) and cervical (91.6%)
      swelling were the commonest presentation. MRI is better than CT scan in
      evaluating fat plane. Transcervical approach was the commonest. In our series,
      benign tumors (83.4%) were common, constituting 50% of neurogenic and 16.6% of
      salivary gland origin. CONCLUSION: PFT were more prevalent in the Asian zone.
      Neurogenic tumors were commonest in our study which contradicts the WWWS of
      having maximum PFT of salivary gland in origin.

PMID- 23120618
TI  - Cerebrospinal fluid rhinorrhea: endoscopic repair based on a combined diagnostic
      approach.
AB  - BACKGROUND: The treatment of cerebrospinal fluid rhinorrhea has evolved since the
      first recorded instance of this condition by Willis in 1676. The advancements in
      radiology and endoscopic nasal surgery have provided ways to solve this
      potentially dangerous condition. But even now quite a few questions remain
      unanswered while tackling this difficult clinical situation. Laboratory tests for
      confirming the presence of cerebrospinal fluid in nasal fluid can yield false
      positive results and radiological evaluation has never been foolproof when it
      comes to small leaks and multiple leaks. Also the postoperative recurrence needs
      to be brought within acceptable limits. OBJECTIVES: We have tried to evaluate
      endoscopic repair of CSF rhinorrhea based on a combined diagnostic approach. The
      methods for diagnosis of CSF rhinorrhea have been reevaluated based on our
      experience with a view to prevent recurrences and complications. MATERIALS AND
      METHODS: The study group included twenty patients of CSF rhinorrhea who have been
      treated by endoscopic repair and spans over a period of five years from January
      2001 to December 2005. A combination of retrospective and prospective methods of
      study has been used. Patients have been subjected to laboratory, radiological and
      dye studies for confirmation and localization of leak. Endoscopic repair of CSF
      fistula with composite graft and fibrin glue has been performed. Postoperative
      management included intracranial pressure reducing measures and control of
      primary condition in cases of spontaneous leak. RESULTS: Endoscopic repair of CSF
      rhinorrhea produced a first time success rate of 92%. CT/MR Cisternogram could
      localize the defect in 85% cases while intrathecal fluorescein aided localization
      whenever it was used. The use of fibrin glue with composite graft and
      postoperative intracranial pressure reducing measures could improve the success
      rate. CONCLUSION: Management of a suspected CSF leak requires a combined
      diagnostic approach. Endoscopic repair with composite graft and fibrin glue
      should be the first line of management in cases of CSF rhinorrhea requiring
      surgical closure. Intracranial pressure reducing measures play an important role
      in preventing postoperative recurrence.

PMID- 23120619
TI  - Soft phonation index - a sensitive parameter?
AB  - OBJECTIVE: The diagnosis of voice disorders is based on perceptual and acoustic
      paradigms. Modern acoustic analysis systems are relatively inexpensive and user
      friendly. One aspect of laryngeal function that is of great interest is the
      extent of vocal fold closure. Soft phonation index (SPI) is the parameter in
      Multi Dimensional Voice Program, which reflects the approximation of vocal folds.
      High values of SPI are stated to correlate with incomplete vocal fold adduction
      and are a better indicator of breathiness than EGG. This study aims to determine
      the sensitivity of this acoustic parameter of SPI, as a reflective indicator of
      incomplete vocal fold adduction in male patients diagnosed with unilateral vocal
      nodules. METHODOLOGY: 60 participants were included in the study; 30 with normal
      vocal fold functioning in the control group and 30 with unilateral vocal nodules
      in the experimental group. The phonation sample of vowel /a/ was recorded into
      CSL 4150 of Kay Elemetrics, in a sound treated room. The readings of SPI on the
      MDVP analysis was extracted and subjected to statistical analysis using
      independent samples 't-test' using SPSS Version 11. RESULTS: The results of the
      study reveal that there was a statistically significant difference between the
      means of the SPI values between the control and the experimental groups.
      DISCUSSION: It can be understood that SPI is a sensitive parameter to detect
      abnormalities in vocal fold approximation in the considered population of
      individuals with vocal nodules. This is in coherence with a study done on
      patients with vocal fold palsy and cordectomy, wherein SPI was found to be a good
      indicator of breathiness. The SPI mean obtained for participants in the control
      group was higher than the Western normative mean specified in MDVP, which
      highlights the importance of establishing normative values for Indian population.
      CONCLUSION: It can be concluded that SPI was sensitive to detect changes
      affecting vocal fold closure in unilateral vocal nodules. But this conclusion has
      to be generalized with caution keeping in mind that only one population with
      vocal pathology was studied. The factors of vocal fold physiology and mechanical
      properties of vocal tract, which may contribute to individual variations in SPI
      values, have to be considered for further research.

PMID- 23120620
TI  - A comparative study of different graft materials used in myringoplasty.
AB  - Two hundred twenty cases of unilateral chronic suppurative otitis media (CSOM)
      with dry central perforation were chosen for this study and myringoplasty were
      done. Age group ranged from 13 to 48 years. Four types of autogenous tissues were
      used as graft material. Grafting was done by underlay technique when temporalis
      fascia, tragal perichondrium, areolar tissue were used as graft material and when
      fat graft was used the ear lobule fat was placed directly into perforation
      through transcanal route. Postoperative follow-up was carried out up to 6 months.
      In this study, it was found that the younger age group has less impairment of
      hearing and better chance of tympanic membrane perforation closure than the older
      age group in CSOM with central perforation. Anterior perforations has less
      impairment of hearing and better result in successful closure of tympanic
      membrane than posterior perforation group. It was also observed that larger the
      size of perforation greater is the hearing impairment preoperatively and
      postoperative hearing gain is also less compared to small perforation. Best
      hearing improvement occurred using temporalis fascia. Failure occurred may be due
      to postoperative infection, respiratory tract infection, neglected post-operative
      advice etc.

PMID- 23120621
TI  - The Bortnick Miller apparatus: a useful alternative to impedance audiometer for
      assessment of eustachian tube function in chronic suppurative otitis media.
AB  - Eustachian tube function was assessed by impedance audiometer and Bortnick Miller
      apparatus in 60 ears with central perforation in pars tensa. Result of both the
      instruments were compared and presented.

PMID- 23120622
TI  - Comparative study of outcome of type I tympanoplasty in dry and wet ear.
AB  - Chronic suppurative otitis media is a common condition seen in patients attending
      the otolaryngology clinic. The discharging ear presents the otologist with the
      dilemma of operating on it or not. This due to the widespread belief that the
      success rate while doing tympanoplasty on wet ears is decidedly inferior. To
      evaluate this fact we conducted a study to compare outcomes of type 1
      tympanoplasty in dry and wet ears. Wet ear meant that the patient had a mild
      mucoid discharge which was negative on culture. Type 1 tympanoplasty was done in
      all patients under local anesthesia using temporalis fascia graft and by underlay
      technique. We conclude that the presence of discharge in the ear at the time of
      operation does not interfere with the results of tympanoplasty, but it should be
      mucoid and scanty.

PMID- 23120623
TI  - Clinicopathological profile of cervicofacial masses in pediatric patients.
AB  - Four hundred pediatric patients (0-12 years of age) who presented with
      cervicofacial masses were evaluated clinically and pathologically. Infl ammatory
      lesions were the commonest (48%) followed by congenital and developmental
      malformations (26%). In infl ammatory lesions, reactive lymphadenopathy was the
      commonest (16%) followed by tubercular lymphadenitis (11.5%). In congenital and
      developmental malformations hemangiomas were the commonest (12%) followed by TG
      cyst (6.5%). Cystic lesions (non-developmental) constituted 19%, benign
      neoplastic lesions 7% and malignant neoplastic lesions 2% of the cases. Males
      predominated the series (53.5%) and commonest age group involved was 10-12 years
      (20.5%). FNAB was performed in 93% of cases and HPE was available in 51.5% of
      cases. Sensitivity of FNAB in our series was 87.4%.

PMID- 23120624
TI  - Innovative surgical management of large vallecular cysts.
AB  - Vallecular cysts are rare and vary from small cysts to large ones occupying the
      whole vallecula obscuring the view of the larynx. In the latter situation careful
      assessment and planning of airway management is required as in our case.

PMID- 23120625
TI  - Role of vitamin A in the evolution of cholesteatoma.
AB  - The role of vitamin A in the maintenance of epithelial integrity is well known.
      Several animal studies have dealt with the induction of cholesteatoma in vitamin
      A deficiency states and prevention and treatment of otitis media with vitamin A
      treatment. We treated five patients of cholesteatoma with vitamin A oral
      supplements and no other treatment and found significant resolution of
      cholesteatoma in four patients. Though this may not be an explanation in every
      case of cholesteatoma, our study highlights that there is a subset of patients
      with vitamin A deficient cholesteatoma who could substantially benefit from
      intervention with this wonderful vital amine.

PMID- 23120626
TI  - Orthodontic treatment after adenoidectomy patients: effect on jaw relations in
      saggital plane.
AB  - Adenoid hypertrophy is a normal phenomenon seen in young children. Adenoids may
      however be of large size or may not reduce in size in adulthood. Large adenoids
      may cause mouth breathing, overcrowding of teeth or otological symptoms. When
      adenoids are large and producing these effects, adenoidectomy is necessary.
      Adenoidectomy immensely benefits such patients but they may still continue to be
      habitual mouth breathers. This can lead to formation of long narrow face,
      labially protruded maxillary incisors and class 2 malocclusion. Immediate
      orthodontic treatment of such patients will improve facial profile and lead to
      class 1 (Angle) occlusion. We present here a study of 20 patients who were given
      early orthodontic treatment in postadenoidectomy period as compared to those
      patients who were not treated by orthodontist.

PMID- 23120627
TI  - Importance of newborn hearing screening.
AB  - US Preventive Services Task Force recommends universal screening of all newborns
      for early detection of hearing impairment and early intervention to prevent its
      effects on normal development and acquisition of language skills. During
      comparison of universal screening of all newborns versus targeted screening of
      high risk cases to detect hearing impairment, it emphasized the importance of
      Universal newborn hearing screening (UNHS) among neonatologists, pediatricians as
      well as ENT specialists taking care of newborns and young children. Among those
      who had early versus late confi rmation of hearing loss and those who had
      undergone universal newborn screening versus none, better language outcomes at
      school age were found than those not screened. Infants identifi ed with hearing
      loss through universal newborn screening had earlier referral, diagnosis, and
      treatment than those not screened. Targeted screening of newborns with high risk
      criteria missed 50% of cases of hearing impairment, either because infants were
      hearing impaired but did not meet any of the high- risk criteria, or because they
      developed hearing loss after the newborn period.

PMID- 23120628
TI  - CT scan evaluation of the anatomical variations of the ostiomeatal complex.
AB  - INTRODUCTION: Functional endoscopic sinus surgery (FESS) has revolutionized the
      approach and treatment of chronic rhinosinusitis. Certain anatomical variations
      are thought to be predisposing factors for the development of sinus disease and
      it is necessary, for the surgeon to be aware of these variations, especially if
      the patient is a candidate for FESS. OBJECTIVE: The aim of the present study was
      to identify the various anatomical variations of the ostiomeatal complex in
      patients of chronic rhinosinusitis who underwent FESS. MATERIALS AND METHODS: A
      total of 150 patients of chronic rhinosinusitis (medical treatment failures) who
      were subjected to FESS were CT scanned preoperatively to find any bony anatomic
      variation and the extent of mucosal disease. RESULTS: Concha bullosa was the
      commonest anatomic variation and was seen in 45 (30%) patients. The other
      anatomic variations noted included: paradoxical middle turbinate in 9.33%
      patients, uncinate process variations in 25% patients, agger nasi cells in 9.33%,
      Haller cells in 8.66% and posterior septal deviations in 25.33% patients. The
      mucosal disease was most commonly seen in anterior ethmoids (87.33% ), followed
      by maxillary sinus ostial area (70%), maxillary sinus disease (65.33%), posterior
      ethmoidal disease (38%), frontal sinus disease (15%) and sphenoid sinus mucosal
      disease (8.66%) patients. CONCLUSION: A thorough preoperative CT evaluation of
      the patients undergoing FESS is necessary to detect various anatomical variations
      in the ostiomeatal complex.

PMID- 23120629
TI  - Inflation-deflation test as a predictor of aditus patency in patients with
      chronic suppurative otitis media.
AB  - AIMS: To assess eustachian tubal function (ETF) preoperatively in patients with
      chronic suppurative otitis media (CSOM) with central perforation by performing
      the inflation-deflation test. To correlate the results of the inflation-deflation
      test with the finding of aditus patency or block in patients with CSOM  STUDY
      DESIGN: Prospective, cohort SETTING: Tertiary care hospital SUBJECTS: Eighty
      adult patients with chronic suppurative otitis media and central perforation were
      recruited into the study. There were 45 males and 35 females. METHODS: All
      patients underwent preoperative inflation-deflation test followed by cortical
      mastoidectomy and tympanoplasty. The patency of the aditus was assessed
      intraoperatively. MAIN OUTCOME MEASURE: Equalization of pressure on inflation
      deflation test and intraoperative assessment of aditus patency RESULTS: Of a
      total of 80 patients, 49 patients were found to have discharging ears and 31 had
      dry ears at the time of surgery. In dry ears the inflation-deflation test had a
      sensitivity of 93% in predicting aditus patency although the specificity was
      lower at 67%. In discharging ears the sensitivity in predicting aditus patency
      was 72% and the specificity was 67%. CONCLUSION: The eustachian tube inflation
      deflation test is a sensitive test for predicting aditus patency in patients with
      dry ears but less so in patients with discharging ears. Hence, it could be used
      in the former to avoid unnecessary exploration of the mastoid.

PMID- 23120630
TI  - Changing trends in otorhinolaryngological diseases at a non-government clinic in
      Jaipur.
AB  - BACKGROUND: Otorhinolaryngological (ENT) diseases are major health problem in
      India but the trends in occurrence of various disorders in clinical practice have
      not been well studied. To assess the types of such diseases and to determine
      changing trends in their incidence we performed this study. METHODS: The study
      was done at a non-government ENT center at Jaipur. From 1975 to 2005, >125000
      patients of different diseases were evaluated here. The study includes randomly
      selected patients (n = 11454) from years 1980 to 2000 at an interval of 5 years
      to evaluate disease trends. Significance of trends was evaluated using least
      squares regression. RESULTS: In the years 1980, 1985, 1990, 1995 and 2000 mean
      age of patients was 26.60 +/- 17.81 (range 0.16 to 85), 27.07 +/- 16.91 (0.08 to
      90), 28.30 +/- 17.73 (0.25 to 90), 28.79 +/- 17.8 (0.25 to 90) and 28.74 +/-
      17.81 (0.25 to 85) years respectively. 51 types of ENT diseases were observed of
      which 19 contributed to 76.8% (8807) patients and analysis was restricted to
      them. Chronic suppurative otitis media (2203, 19.2%), otitis externa (859, 7.5%),
      deviated nasal septum with nasal obstruction (717, 6.3%) and chronic tonsillitis
      (695, 6.1%) were the most common, followed by ear wax (569, 4.9%), sensorineural
      hearing loss (545, 4.7%), chronic rhinosinusitis (428, 3.7%) and epistaxis (320,
      2.8%). There was increasing trend for stomatitis (b = 0.0014), deviated nasal
      septum (b = 0.0290), allergic rhinitis (b = 0.0023), epistaxis (b = 0.0002),
      acute tonsillitis (b = 0.0003), hoarseness (b = 0.0017), deaf mutism (b =
      0.0005), sensorineural hearing loss (b = 0.0038), tinnitus (b = 0.0006) and ear
      wax (b = 0.0050). Declining trend was observed for chronic rhinosinusitis (b = 
      0.0155), otitis externa (b = -0.0063), chronic suppurative otitis media (b = 
      0.0001), acute otitis media ( = -0.0007), secretory otitis media (b = -0.0013),
      otosclerosis (b = -0.0007), vertigo (b = -0.0007), neck swelling (b = -0.0005)
      and chronic tonsillitis (b = -0.0194). CONCLUSION: This study from an Indian
      urban ENT center shows a significantly increasing trend in chronic and
      degenerative ear diseases and decline in infection related diseases.

PMID- 23120631
TI  - Nd:YAG laser therapy of carcinoma lip (stage I squamous cell carcinoma): a
      retrospective evaluation.
AB  - OBJECTIVE: To asses the efficacy of Nd:YAG laser for stage I squamous cell
      carcinoma of the lip. To the authors' knowledge this is the first reported study
      on this subject. STUDY DESIGN: Retrospective study design involving treatment of
      46 patients of either sex of stage I squamous cell carcinoma of lip over a 10
      year period in a single tertiary care university teaching hospital with Nd:YAG
      laser. METHODS: Nd:YAG laser ablation of lesions in lip was carried out in all
      the patients on an OPD basis with prior consent. A regular follow-up was
      maintained for a period of 5 years. A negative biopsy at the end of one month and
      one year was considered a treated case. The tabulated data was analysed
      statistically by "Kaplan Meier" method and "Log Rank" test. Also cosmetic and
      functional results were assessed by any sign of flow away after filling the oral
      cavity with water and postoperative integrity of facial nerve in accordance with
      "House Brackmann" classification. RESULTS: In this series of 46 patients, 35
      patients were disease free at the end of 3 years and this number further declined
      to 29 at the end of 5 years with 4 deaths and 2 more patients lost to follow-up.
      The statistical evaluation by Kaplan Meier method gives us an overall 5-year
      survival rate of 88.14% with a mean survival of 58 months. Further 8 patients
      required repeat laserization either for residual or recurrence of lesion. Also 2
      patients had a lymph node metastasis during the follow-up period. Thus, by
      applying Kaplan Meier method recurrence-free survival (RFS) and disease-free
      survival was found to be 85.1% (mean: 55 months) and 73.34% (mean: 57 months
      respectively. Interestingly on applying Log Rank test it was observed that the
      site of the lip involvement, i.e. whether upper or lower had no influence on
      disease-free survival. It was also observed that history of tobacco intake did
      not influence the disease free survival either (Log Rank Test). Moreover the
      cosmetic results were excellent and with no significant complication observed.
      CONCLUSION: The results reported here support the use of Nd:YAG laser for
      treatment of Stage I squamous cell carcinoma of lip in accordance with principles
      of minimal invasive and morbid surgery.

PMID- 23120632
TI  - A comparative study of ceruminolytic agents.
AB  - A prospective study was done to access the efficacy of ceruminolytic agents, i.e
      2% paradichlorobenzene, 10% sodium bicarbonate, 2.5% acetic acid and normal
      saline. All score 4 hard impacted ear wax cases in the adult population (>20
      years) were accrued for the assessment of the relative efficacy. Upon analyzing
      the comparative efficacy of four ceruminolytic agents, by taking into
      consideration three parameters (post) ceruminolytic cerumen score, attempts of
      syringing required to extrude the cerumen mass, post-ceruminolytic use and
      appearance of the removed cerumen mass. 2% paradichlorobenzene emerged as the
      most superior ceruminolytic, closely followed by 10% sodium bicarbonate. 2.5%
      acetic acid fared moderately while normal saline emerged as the least efficacious
      ceruminolytic agent.

PMID- 23120633
TI  - Bacterial contamination of multiple-use atomizers commonly used in Japan.
AB  - Before performing transnasal fiberscopy to observe the nasal cavity, pharynx and
      larynx in outpatient clinics, nasal anesthetics and vasoconstrictive agents are
      routinely sprayed into the nares in order to improve patients' comfort. Bacterial
      contamination of the nozzles of Venturi principle atomizer barrels and their
      solutions after being used for multiple patients over a long-term period without
      cleaning is controversial. We evaluated the potential risk of atomizer-associated
      cross-infection by using atomizers commonly available in Japan that use
      compressed air to atomize medication. Eighteen of the 23 samples (78.3%) from the
      external nozzle tips of the atomizers resulted in positive bacterial cultures.
      These detected bacteria are suggested to be colonized in the nares and to cause
      bacterial contamination of the atomizer. Of the 25 samples obtained from the
      spray of the drug solutions, 11 samples showed positive bacterial culture,
      whereas 16 control samples produced no growth of bacteria. The present study
      demonstrated that the atomizer widely used in the outpatient ENT clinics in Japan
      has a potential risk of causing cross-infection of patients.

PMID- 23120634
TI  - Acute epiglottitis in adults - a recent review in an Indian hospital.
AB  - OBJECTIVES: To examine the mode of presentation, clinical course and treatment of
      acute epiglottitis in a series of adult patients. METHOD: All adults with acute
      epiglottitis admitted to teaching hospital over a period of 12 months were
      included in this retrospective study. The diagnosis of epiglottitis was
      eatablished by laryngoscopy and soft tissue X-ray neck lateral view. RESULTS:
      Twelve patients were included. Three patients had concurrent acute tonsillitis.
      Blood cultures were negative in all the cases. Pathogens were isolated by throat
      swabs only in three patients with acute tonsillitis. Two patients underwent
      intubation for management of airway obstruction. A combination of coamoxy-clav
      and metronidazole was the most common antibiotic regimen used. CONCLUSION: The
      rising incidence of acute epiglottitis in the adults necessitates the close
      observance on the part of the otolaryngologist. Selective airway intervention is
      recommended for patients with more than 50% airway obstruction.

PMID- 23120635
TI  - Staple-assisted endoscopic management of Zenker's diverticula: a role in the
      geriatric population.
AB  - Endoscopic stapling technique (modified Dohlman procedure) for treatment of
      hypopharyngeal diverticula (Zenker) has been shown to produce outcomes similar to
      open techniques but with shorter operating times and shorter hospitalization.

PMID- 23120636
TI  - Dexmedetomidine used to provide hypotensive anesthesia during middle ear surgery.
AB  - This study was carried out to assess the hypotensive effect of low dose
      dexmedetomidine (DEX) infusion during middle ear surgery. 42 ASA grades I and II
      patients of either sex aged 18-45 years undergoing elective middle ear surgery
      were randomly divided into two groups of 21 each. Group I received placebo bolus
      and infusion of saline at a rate similar to DEX in Group II. Group II received 10
      15 min prior to induction of anesthesia 1 ug/kg IV bolus DEX diluted in 10 ml of
      normal saline over 10 min. Immediately thereafter an infusion of 0.4 ug/kg/hr of
      DEX commenced. Standard anesthetic technique was used. Halothane was titrated to
      achieve a mean arterial pressure 30% below the control value (value taken just
      after premedication). We observed that a statistically significant reduction in
      the percentage of halothane required to reduce MAP 30% below control value
      occurred in patients receiving DEX infusion (1.3 +/- 0.4%) in comparison to those
      receiving placebo (3.1 +/- 0.3%). Patients receiving DEX infusion had a better
      surgical field. The mean awakening time was significantly reduced in patients of
      Group II (9.1 +/- 2.7 min) when compared to patients of Group I (12.8 +/- 2.2
      min).We conclude that DEX can be safely used to provide hypotensive anesthesia
      during middle ear surgery.

PMID- 23120637
TI  - Changes in ventilatory function following surgery for bilateral abductor
      paralysis.
AB  - Management of bilateral vocal fold immobility continues to remain a challenge for
      the Otolaryngologist who attempts to create a balance between creation of an
      adequate airway and preservation of voice. The flow volume loop obtained by
      spirometry provides an ideal objective assessment tool to evaluate the results of
      surgery for this condition. Our experience in using peak inspiratory flow rate
      (PIFR) and forced inspiratory flow with 50% of vital capacity (FIF(50)) in the
      lung in assessing the results of surgery is described. Seventeen patients were
      included in the study. The surgical procedures performed included laser posterior
      cordectomy with partial arytenoidectomy, endoscopic arytenoidectomy and posterior
      cordectomy-Kashima's technique. Twelve out of 17 patients were successfully
      decannulated, a success rate of 70.6%. All patients except one showed an increase
      in mid-inspiratory flow rates and peak inspiratory flow rates. The mean increase
      in FIF(50) was 0.44 l/sec (52.6%) and the mean increase in PIFR was 0.41l/sec
      (39.77%). No statistically significant difference in improvement of inspiratory
      flow rates was observed between the three surgical procedures used in the study.

PMID- 23120638
TI  - The epidemiology of laryngeal cancer in a country on the esophageal cancer belt.
AB  - OBJECTIVE: Laryngeal cancer is one of the most common malignant neoplasms of the
      head and neck and occurs predominantly in males. Squamous cell carcinomas arising
      in the glottic region are the most common of all laryngeal cancers and more
      prevalent than the supraglottic ones. But this pattern is reverse in some
      countries. This study was done to investigate the epidemiologic aspect of this
      subject in Iran. STUDY DESIGN: Cross-sectional study SUBJECTS AND METHODS: During
      a ten-year period from 1997 to 2007, all patients referred to two tertiary
      referral hospitals with a diagnosis of laryngeal cancer were enrolled in this
      study. RESULTS: Laryngeal cancer was diagnosed in a total of 453 patients and
      confirmed histologically. The average patient age was 59.92 years. Men
      outnumbered women (9.5:1). Four hundred patients (88.5%) were tobacco smokers.
      The primary location of the tumor was supraglottic in 221 (49%) cases, followed
      by glottic in 163 (36.2%), transglottic (the tumor involved all regions of the
      larynx and the origin was unspecified) in 60 (13.3%), and subglottic in 7 (1.6%).
      CONCLUSION: In our series, although we excluded transglottic tumors, the
      supraglottic tumor was dominant and the ratio of supraglottic to glottic tumors
      was 1.36. This is compatible with results from countries with a reverse ratio.

PMID- 23120639
TI  - The prevalence of otological manifestations in children with cleft palate.
AB  - AIMS: i) To determine the prevalence of the various otological manifestations
      that occured in children aged between 1 to 5 years, presenting to the Departments
      of ENT and Plastic Surgery with overt cleft palate. ii) To evaluate the
      possibility of the association of the different otological manifestations in
      relation to the various types of cleft. MATERIALS AND METHODS: A cross sectional
      study was performed on children with cleft palate presenting to the
      Otorhinolaryngology and Plastic Surgery OPDs of KLE Society's Dr. Prabhakar Kore
      Hospital and MRC (KLESPKH & MRC) (a tertiary referral centre), Belgaum between
      February 1, 2007 and January 31, 2008. Data was collected by clinical ear
      examination and evaluation of tympanometry reports. RESULTS: Prevalence of
      external ear abnormalities in the studied population was 13%. More than 55% of
      the participants' ears were diagnosed clinically with OME. There was no
      statistically significant association between type and side of cleft with the
      presence of OME. CONCLUSION: External ear deformities are more prevalent in the
      cleft palate population than the general population. There was a high prevalence
      of OME in concordance with previous studies. The prevalence of other otopathology
      was rare. There was no association of the type or side of palate cleft with OME.

PMID- 23120640
TI  - Endonasal endoscopic dacryocystorhinostomy: our experience.
AB  - OBJECTIVES: To study the outcome of endonasal endoscopic dacryocystorhinostomy
      (DCR) with or without mucosal flap preservation, without mitomycin local
      application, silicon tube stenting or laser assistance. To determine the duration
      of the surgical procedure of DCR, influence of simultaneously performed endonasal
      endoscopic procedures for concomitant sinonasal diseases. METHODS: Combined
      retrospective and prospective study in our tertiary referral center. 24 patients
      with chronic dacryocystitis underwent 25 standard endonasal endoscopic DCR
      procedures, 10 with and 15 without mucosal flap preservation. 6 of these had
      concomitant sinonasal diseases for which they underwent septoplasty or functional
      endoscopic sinus surgery (FESS) or both, simultaneously or as staged procedures.
      Relief from epiphora and patency of the nasolacrimal fistula was assessed by
      nasal endoscopy and syringing of the lacrimal apparatus at 1 week, 3 weeks and 3
      months postoperatively. RESULTS: Out of 18 patients who underwent only DCR, 17
      patients (94.44%) had complete relief from epiphora. Out of 6 patients who
      underwent 7 DCRs with concomitant sinonasal surgery, 5 patients (85.71%) had
      complete relief from epiphora. Overall 23 out of 25 DCRs (92%) had complete
      relief. In 15 of the 25 procedures, mucosal flap was excised completely. In
      remaining 10 procedures, flap was trimmed, repositioned to cover exposed bone
      around the newly created nasolacrimal fistula. In either situation, only one
      patient each had partial block of the nasolacrimal fistula. Average duration of
      the surgical procedure of DCR was 18 min. CONCLUSION: Endonasal endoscopic DCR is
      a viable alternative to external DCR, co-existing sinonasal diseases can be
      managed simultaneously, as may be required in 25% of cases. It can be performed
      under 20 min without mucosal flap preservation, mitomycin local application,
      silicon tube stenting or laser assistance and can still provide a good success
      rate (92%) with less complications.

PMID- 23120641
TI  - Study of relationship of concha bullosa to nasal septal deviation and sinusitis.
AB  - OBJECTIVES: To study the etiological role of concha bollosa in deviated nasal
      septum (DNS) and sinusitis. MATERIALS AND METHODS: In this retrospective study
      419 consecutive CT scans of paranasal sinuses done between October 2005 and
      September 2007 were serially evaluated for the presence of concha, DNS and
      sinusitis. RESULTS: Out of 419 CT scans evaluated, concha bullosa was present in
      40.3% of patients. Among these, concha co-existent DNS was found in 87.5%, air
      column between DNS and concha was found in 88.5% and sinus disease was present in
      69.2% of patients. CONCLUSION: Presence of air column between DNS and concha
      excludes the etiological role of concha in DNS. Concha bullosa may predispose to
      sinusitis.

PMID- 23120642
TI  - Unusual presentations of thyroid malignancies - a case series.
AB  - Unusual presentations of thyroid neoplasms have been reported from time to time.
      Four such cases of bizarre presentations of thyroid malignancies seen in the ENT
      Department of ESIC Hospital, K.K. Nagar, Chennai, India are presented. These
      cases highlight certain important issues concerning the diagnosis and management.
      A review of the literature on the subject is discussed.

PMID- 23120643
TI  - Peripheral primitive neuroectodermal tumor of head-neck region: our experience.
AB  - To present four rare cases of peripheral primitive neuroectodermal tumors of
      different sites of head and neck region. Four cases of different age (range 8-40
      years) and sex (three female, one male) with rare primitive neuroectodermal tumor
      of sinonasal region and neck are presented. Treatment options, biological
      behavior and prognostic outcome are discussed herewith. Two patients succumbed to
      the disease within four to six months of treatment; other two patients are still
      under follow-up depicting the aggressive nature of the tumor. Primitive
      neuroectodermal tumor belongs to the class of malignant round cell tumor.
      Immunohistochemistry plays a pivotal role in differentiating this tumor entity.
      Chemoradiation was tried, but local and systemic spread occurs early and holds
      poor prognosis. This case series is an attempt to describe the aggressive
      behavior of this rare tumor with high mortality.

PMID- 23120644
TI  - Benign jaw tumors.
AB  - The jaw bones may develop the same types of tumors as the other bones of the body
      but may also develop tumors arising from the alveolar processes (epulis) and the
      developing teeth (odontomes). They are usually benign in nature and can affect
      the functions of mastication, swallowing and cause facial deformity. They make
      about 3% of all bone tumors with a tendency for a local recurrence if a wide
      excision is not contemplated at the first attempt. Local destruction caused by
      the tumor can mimic a malignancy; however with imaging we can get a fair idea
      about the treatment planning. We present a series of 6 cases of such nature for
      their variety, diagnostic challenge they posed and different reconstruction
      methods used for better cosmesis.

PMID- 23120645
TI  - Totally implantable hearing aid surgical technique and the first Indian
      experience with Envoy esteem.
AB  - Hearing aids are the principal means of auditory rehabilitation for patients with
      moderate to severe sensorineural hearing loss. Although technical improvements
      and modifications have improved the fidelity of conventional aids, hearing aids
      still have many limitations. Implantable hearing aids offer patients with hearing
      loss several potential advantages over conventional hearing aids. This
      presentation will highlight our first experience, the indications, the procedure,
      the advantages and the current status of totally implantable hearing aids.

PMID- 23120646
TI  - Assessment of aminoglycoside-induced hearing impairment in hospitalized neonates
      by TEOAE.
AB  - CONTEXT: Aminoglycosides, as potent bactericidal antibiotics against aerobic gram
      negative infections, is still widely used, especially in NICU patients, despite
      their known potential ototoxic effects. AIMS: To evaluate the potential of
      transient evoked otoacoustic emissions (TEOAEs) in early identification of
      decreased hearing sensitivity in hospitalized neonates receiving aminoglycosides
      for severe gram-negative infections. MATERIALS AND METHODS: Fifty (50) neonates
      treated with intravenous gentamicin (5 mg/kg/day) or amikacin (15 mg/kg/day) were
      tested with TEOAE in the beginning and the end of aminoglycoside therapeutic
      course. There were 23 males and 27 females, ranging from 29 to 40 weeks (mean: 36
      weeks). The treatment duration was 3-30 days (in 26 neonates up to 7 days - group
      A, and in 24 neonates higher than 7 days - group B). RESULTS: In group A, no
      statistically significant difference in the mean response level was found between
      the onset and the end of treatment course (p > 0.001). In group B, a
      statistically significant difference in the mean response level was found between
      the onset and the end of treatment course, especially at high frequency region (p
      < 0.001). CONCLUSIONS: TEOAE is sensitive enough to detect early aminoglycoside
      ototoxicity. As this test is simple to perform, non-invasive and reliable, so we
      suggest that TEOAE test should be performed in NICU as routine for monitoring
      cochlear function to prevent permanent hearing loss especially in those who are
      receiving aminoglycoside for more than 7 days.

PMID- 23120647
TI  - Significance of styloidectomy in Eagle's syndrome: an analysis.
AB  - OBJECTIVES/HYPOTHESIS: Reported here is a randomized retrospective analysis of 28
      cases of elongated styloid process causing nagging cervicofacial pain, both
      unilateral and bilateral, and the effect of styloidectomy in these cases in
      relieving the symptom complex of the patient, in situations where conservative
      management failed in alleviating the symptoms. STUDY DESIGN: Randomized
      retrospective analysis over a period of 25 months. CONCLUSION: Elongated styloid
      process causing glossopharyn-geal neuralgia is beginning to be a frequently
      encountered clinical entity nowadays. Of the 28 cases of elongated styloid
      process who underwent unilateral/bilateral styloidectomy, 27 patients had total
      relief of symptoms. Hence, we advocate styloidectomy, following careful diagnosis
      of the entity with clinical and radiological correlation, if the patient does not
      respond to medical therapy. The psychological status of the patient would provide
      clue to the authenticity of the symptoms in unrelieved cases.

PMID- 23120648
TI  - Results of intravenous steroid injection on reduction of postoperative edema in
      rhinoplasty.
AB  - OBJECTIVE: To determine the efficacy of intravenous dexamethasone in reducing
      postrhinoplasty edema. DESIGN: A prospective, randomized clinical trial with
      placebo control. SETTING: Department of Otorhinolaryngology, Al-Sabah and Zain
      Hospital, Kuwait. SUBJECT: Eighty-four patients (male = 28; female = 56) aged
      between 20 and 40 years, undergoing open rhinoplasty with hump removal and
      bilateral lateral osteotomies were enrolled in this study. INTERVENTION: Patients
      were randomized to receive two doses of 10 mg of dexamethasone intravenously or
      placebo, first dose during surgery and second dose 12 hours after surgery. MAIN
      OUTCOME MEASURES: Patients were evaluated postoperatively at 24 hours, days 2, 5,
      7 and 10 for periorbital edema. RESULTS: 10 mg of dexamethasone given
      intravenously during rhinoplasty and a second dose 12 hours after surgery,
      reduced postoperative periorbital edema significantly. CONCLUSION: This study
      showed a statistically significant benefit of dexamethasone over placebo in
      reducing periorbital edema after rhinoplasty. No complications were attributed to
      the administration of dexamethasone.

PMID- 23120649
TI  - Cancer of the external auditory canal-diagnostic and treatment.
AB  - BACKGROUND: Ear squamous cell carcinoma (SCC) is a tumor with a poor prognosis,
      due to a late initial diagnosis because of a concealment by primarily benign
      symptoms and due to the unfavorable localization including the infiltration of
      important structures such as the middle ear, mandibular joint or dura. PATIENTS
      AND METHODS: We retrospectively examined 10 patients, medium age: 63.8 +/- 9.3
      years between 2002 and 2008 with a histological confirmed SCC of the external
      auditory canal. The median follow-up period was 20.5 months (range 7-60 months).
      RESULTS: The treatment involving surgery, radiotherapy and/or chemotherapy
      yielded a survival rate of 38.3 +/- 11.3 months for T1 and a survival rate of
      17.0 +/- 3.0 months for T2-T4 tumors. 3/10 patients at T1 stage are under follow
      up, all 7/10 (70%) patients at T2 and T4 stage did not survive 5 years.
      CONCLUSION: The prognosis for ear SCC primarily depends on early clinical and
      histopathological diagnostics and requires a sufficient and standardized staging
      to determine the therapy involving surgery and radiochemotherapy.

PMID- 23120650
TI  - Hypertensive retinopathy and sensorineural hearing loss.
AB  - OBJECTIVE: To determine the correlation between hypertensive retinopathy (which
      is the end-organ damage of the vessels due to chronic hypertension) with
      sensorineural hearing loss. METHODS: Pure tone hearing threshold of 56
      hypertensive patients were compared with 56 normal age and sex matched control.
      Comparisons of pure tone hearing threshold are made among different group (grade)
      of hypertensive retinopathy patients and control (non-hypertensive patients).
      RESULTS: The mean hearing thresholds were higher (worse) in all the frequencies
      on both sides in the hypertensive study group compared with normal subjects.
      However it was found to be statistically significant when tested using
      independent sample test (p < 0.05) on right ear at 2,000 Hz, 4,000 Hz and 8,000
      Hz only. The mean hearing threshold is higher in all frequencies in the presence
      of retinopathy compared to control. However, the difference was found to be only
      statistically significant in the mean hearing threshold between grade I and
      control at 4,000 Hz and 8,000 Hz on both sides and at 1,000 Hz and 2,000 Hz on
      right ear. Hypertensive patient with grade I retinopathy had higher pure tone
      hearing thresholds at 4,000 Hz and 8,000 Hz compared to hypertensive without
      retinopathy and normal control. CONCLUSIONS: Hypertensive retinopathy appears to
      be associated with high frequency sensor neural hearing loss.

PMID- 23120651
TI  - Permanent hypocalcemia in patients operated for thyroid carcinoma.
AB  - AIM AND OBJECTIVE: The incidence and risk factors for permanent hypocalcemia in
      thyroid carcinoma were investigated. MATERIALS AND METHODS: The records of 417
      patients were reviewed retrospectively at tertiary oncology referral center.
      Total or subtotal thyroidectomy patients constituted group I (n = 225),
      reoperative thyroid surgery patients constituted group II (n = 106), and
      therapeutic neck dissection cases constituted group III (n = 86). Age, gender,
      thyroid functions, pathologically verified tumor type, differentiation,
      localization and size, multicentricity, thyroid capsule invasion, extrathyroidal
      soft tissue invasion, coexistence of lymphocytic thyroiditis, metastatic lymph
      nodes dissected, incidental parathyroidectomy, and the type of surgery were
      investigated.  RE SULTS: Permanent hypocalcemia was seen in 32 (7.7%) patients.
      The incidence of permanent hypocalcemia for each group was 1.7%, 10.3% and 19.7%,
      respectively. Related risk factors were hyperthyroidism for group I [adjusted
      relative risk (RR) = 21.1, 95% confidence interval (CI) = 2.6-165, p = 0.01]
      incidental parathyroidectomy for group II (RR = 7.8, 95% CI = 1.9-31.0, p =
      0.004), and extrathyroidal soft tissue invasion (RR = 3.1, 95% CI = 1.1-9.5, p =
      0.03) for group III. CONCLUSION: Permanent hypocalcemia rate was increased with
      reoperative thyroid surgery and neck dissection added to total thyroidectomy.
      Hyperthyroidism, incidental parathyroidectomy and extrathyroidal extension were
      related risk factors.

PMID- 23120652
TI  - Effects of radiotherapy on parotid salivary sialochemistry in head and neck
      cancer patients.
AB  - AIM: To determine the effects of high dose irradiation on parotid salivary sodium
      and pH concentration at subsequent duration of 1.5, 3 and 6 months following
      radiotherapy. MATERIALS AND METHODS: Eighty parotid glands of head and neck
      cancer patients were irradiated with mean dose of 66 Gy. The stimulated parotid
      flow (PF) was collected by a cannulation of Stenson's duct followed by analysis
      of sodium (PF sodium) by Easylyte Sodium/Potassium auto analyzer and pH by litmus
      narrow band pH paper. RESULTS: A steep elevation of PF sodium was found in post
      RT period after 1.5 months of starting RT followed by gradual increase up to 6
      months and pH changed towards acidity. CONCLUSIONS: A high dose of 66 Gy causes
      irreversible damage to parotid salivary duct system.

PMID- 23120653
TI  - Clinicopathological study of otogenic brain abscess.
AB  - Chronic suppurative otitis media (CSOM) is one of the commonest disease entities
      encountered in otolaryngology practice. Due to poor economic conditions poor
      hygiene lack of education and death of knowledge about the disease and its
      complications, we frequently encounter patients of CSOM with extracranial and
      intracranial complications. Among the intracranial complications otogenic brain
      abscess is one of the dreadest. With the improvement of healthcare and
      accessibility of the poor people to healthcare system and development of CT scan,
      MRI as diagnostic tools incidence of otogenic brain abscess is becoming less due
      to early diagnosis and interventions. The objectives of this study are to assess
      the incidence of brain abscesses to explore age, sex, variation to study clinical
      presentations and common pathogens responsible.

PMID- 23120654
TI  - Prospective study of myringoplasty using different approaches.
AB  - BACKGROUND: Myringoplasty is one of the various surgical techniques for the
      management of chronic supurative otitis media of tubotympanic type (CSOM-TT). The
      presence of a perforation of tympanic membrane with intermittent discharge and
      hearing loss of conductive nature are the indications of myringoplasty.
      Myringoplasty can be performed by any of the three approaches, i.e. permeatal,
      endaural, or post-aural. It is a beneficial procedure done for closing tympanic
      membrane perforation and improving hearing. OBJECTIVE: The aim of this study was
      to evaluate and compare different approaches of myringoplasty and various factors
      influencing surgical outcome. MATERIALS AND METHODS: Myringoplasty was done in 90
      cases of tympanic membrane perforation with temporalis fascia graft by underlay
      or onlay technique through one of the three approaches, i.e. permeatal, endaural
      and post-aural. RESULTS: The overall success rate in this study was 81.11% with
      majority of patients had improvement in hearing. Statistically there was no
      significant difference in results with different approaches. Age, sex, site, size
      and duration of disease had no bearing on graft take in this study. CONCLUSION:
      In repairing tympanic membrane perforations similar success rates are achieved
      with postaural or endaural approaches. A permeatal approach is most limited in
      the exposure obtained. What is important in choosing the appropriate approach is
      the location and size of the perforation and size of external auditory canal.

PMID- 23120655
TI  - Acute epiglottitis: a retrospective review of 47 patients in Kuwait.
AB  - OBJECTIVES: Acute epiglottitis is a potentially life threatening condition which
      can lead to fatal airway obstruction in previously healthy individuals. The
      present study was undertaken to assess the clinical features, management and
      patient outcomes of epiglottitis in Kuwait over an eight year period. DESIGN:
      Case series. SETTING: Al Sabah Hospital, Kuwait. METHODS: All patients admitted
      to the ENT department of Al Sabah hospital between January 2000 and January 2008
      with the diagnosis of acute epiglottitis were included in this retrospective
      study. The diagnosis of acute epiglottitis was established by visualization of
      inflamed epiglottis either on indirect laryngoscopy or flexible fibreoptic/direct
      laryngoscopy. RESULTS: 47 cases were identified, 5 children and 42 adults. There
      were 32 males and 15 females, in the age range of 5 to 66 years. Peak incidence
      was in the third decade. 31 patients had co-morbid conditions, 18 patients
      (38.2%) had diabetes, 8 patients (17%) had hypertension and 3 patients (6.3%) had
      dental caries. Majority of the patients (89.3%) presented with sore throat as
      their chief complaint. All patients were febrile on presentation. The classical
      "thumb sign" on lateral neck radiograph was seen in 32 patients (68%). Blood
      cultures were collected from 22 patients (46.8%), all were negative. Ceftriaxone
      was the commonest empirical antibiotic prescribed. 7 patients required airway
      intervention (5 with endotracheal intubation and 2 with tracheostomy). There were
      no deaths in our study. CONCLUSION: In Kuwait, acute epiglottis is commoner in
      adults than in children. It is imperative to secure the airway and to start the
      patients on broad spectrum antibiotics and steroids as early as possible. In
      general, the prognosis is good with antimicrobial therapy, close monitoring and
      selective airway intervention, in the form of intubation / tracheostomy, for
      patients with stridor or shortness of breath.

PMID- 23120656
TI  - Management of laryngotracheal stenosis - our experience.
AB  - OBJECTIVE: To describe our experience in the management of laryngotracheal
      stenosis (LTS). STUDY DESIGN: Prospective study. MATERIALS AND METHODS: This
      study was carried out from 2001 to 2004 on 30 cases. All cases were investigated
      by spiral computerized tomography and endoscopic examination. RESULTS: There were
      21 males and 9 females treated for LTS resulting from trauma (19), intubation (9)
      and congenital (2). Patients were divided into four groups based on surgical
      procedures they underwent: group I, endoscopy dilatation group (7 cases); group
      II, laryngotracheoplasty with Montgomery tube insertion (12 cases); group III,
      laryngotracheoplasty with Montgomery laryngeal stent insertion (5 cases) and
      group IV, cricotracheal resection with M-tube insertion (6 cases); The number of
      patients decannulated in group I, group II, group III and group IV were 4, 10, 0
      and 5, respectively. We found statistically significant difference between
      decannulated and nondecannulated group for site and length of stenosis.
      CONCLUSION: Patients undergoing dilatation for LTS require multiple procedures.
      Open surgical exploration with stent has a better outcome than those with
      repeated dilatation.

PMID- 23120657
TI  - Management of penetrating zone II neck injuries.
AB  - The incidence of penetrating and lacerated neck injuries has been on the rise
      recently because of the increase in road traffic mishaps. Clothesline injuries
      are injuries caused by striking against a stationery object like a wire or tree
      limb. Most of the times these end up causing blunt injuries with associated
      fracture of the laryngeal framework. Here we report two cases of penetrating neck
      injuries with successful outcomes and also the problems encountered in the
      management of these cases. A proper evaluation, rapid airway intervention and
      proper surgical repair are essential for a successful outcome.

PMID- 23120658
TI  - Rhabdomyosarcoma of nose, nasopharynx and paranasal sinuses.
AB  - Rhabdomyosarcoma is an aggressive malignant soft tissue tumor that arises from
      primitive striated muscle cells called rhabdomyoblasts. It is the most common
      soft tissue malignant tumor in children and accounts for about 7-8% of childhood
      cancers. It can arise from almost anywhere in the body but it is most common in
      the head and neck region. This article presents six cases of rhabdomyosarcoma
      involving the nose, nasopharynx and the paranasal sinuses four of which were
      treated with a combination of radiotherapy and chemotherapy and two were treated
      with medial maxillectomy combined with chemotherapy and radiotherapy.

PMID- 23120659
TI  - Rupatadine: pharmacological profile and its use in the treatment of allergic
      rhinitis.
AB  - Rupatadine is a once-daily, non-sedating, selective and long-acting new drug with
      a strong antagonist activity towards both histamine H1 receptors and platelet
      activating factor receptors. The use of rupatadine is indicated in adult and
      adolescent patients (>12 years of age) suffering from intermittent and persistent
      allergic rhinitis. In the treatment of these conditions, rupatadine is at least
      as effective as ebastine, cetirizine, loratadine and desloratadine. Avery good
      safety profile of rupatadine has been evidenced in various studies, including a
      long-term (1-year) safety study. Rupatadine does not present drug-drug
      interactions with azithromycin, fluoxetine and lorazepam, but should not be
      administered concomitantly with known CYP3A4 inhibitors.

PMID- 23120660
TI  - Is dynamic MM a suitable method for every sleep apnea patient ?

PMID- 23120661
TI  - Controversies and dilemmas in laryngopharyngeal reflux disease: a new paradigm of
      airway manifestations of a gastrointestinal disease.

PMID- 23120662
TI  - Prevalence of head and neck cancers in Ahmedabad, Gujarat.
AB  - INTRODUCTION: Head and neck cancer constitute one of the commonest cancers in
      India. Use of smokeless tobacco (pan masala, gutka, zarda, etc.) is the maximum
      in Gujarat, especially in and around Ahmedabad, and it is responsible for a large
      majority of these cancers. AIM AND OBJECTIVE: The present study was carried out
      to study the patient's characteristics, prevalence, treatment modalities and
      histopathological subtypes of head and neck cancer in and around Ahmedabad.
      METHODS: A cross-sectional and observational study was carried out at the Head
      and Neck Services Department of Aastha Oncology Associates, Medi-Surge Hospitals,
      Ahmedabad, from December 2006 to May 2007. Patients were made to fill up the Case
      Record Form (CRF) with their informed consent. Proforma of the CRF included
      patient's age, gender, income, education, family history, lifestyle, signs and
      symptoms, various investigations, treatment options and adverse effects during
      treatment and follow up. Preponderance of cancer was found in males (86%) with
      maximum prevalence in age group 41-60 years (69%). 58% cases were habitual
      tobacco chewers. Majority of head and neck cancers constituted the tongue, buccal
      mucosa and alveolus cancers. Radiotherapy and surgery were major treatment
      options in 44% patients. Blood parameters profile in all the three treatment
      groups was found to be lower than the control group. CONCLUSION: We conclude that
      a properly structured and site specific data like this pin points to the
      magnitude and pattern of head and neck cancer problem in India and it can augment
      the National Cancer Registry Program.

PMID- 23120663
TI  - Juvenile nasopharyngeal angiofibroma-our experience at a referral hospital.
AB  - Nasopharyngeal angiofibroma is a rare, highly vascular locally invasive tumor
      with a strong tendency to bleed. It usually occurs in young adolescent males.
      This is a retrospective study of 53 patients with nasopharyngeal angiofibroma.
      All the cases were treated surgically by different conventional approaches
      depending upon the extent of the mass. Transpalatal approach was used in 32
      cases, lateral rhinotomy in 13 cases and a combination of transpalatine + lateral
      rhinotomy + caldwel-luc in 8 cases. There is no recurrence in 49 cases till date.
      However, recurrence was noted in four cases within six months. Three out of four
      patients with recurrence had to undergo repeat surgery for the removal of
      angiofibroma within six months while the remaining one was referred to
      radiotherapy as the mass was invading the cavernous sinus. The various clinical
      presentation and treatment modalities are discussed.

PMID- 23120664
TI  - Use of diode laser in oral submucous fibrosis with trismus: prospective clinical
      study.
AB  - INTRODUCTION: Oral submucous fibrosis (OSMF) in later stages invariably leads to
      trismus due to retromolar fibrosis and buccal mucosa involvement. Medical
      treatment has limited role once trismus is established. Various surgical methods
      have been used with varying success to relieve trismus. We used diode laser to
      relieve trismus. All patients were diagnosed to have OSMF with trismus. The
      results are quite encouraging. STUDY DESIGN: Prospective clinical study. This
      study involved 8 patients between the years 2002 and 2006. OBJECTIVE: To evaluate
      the efficacy of laser to reduce trismus in OSMF  METHODS: Laser with follow-up
      physiotherapy CONCLUSION: Diode laser gave good result in all our patients. Diode
      laser is a less expensive and alternative method in group III and group IVA cases
      in whom bilateral temporalis myotomy and coronoidectomy are considered to be the
      only solution. This technique has less morbidity and is suitable for Asian
      population as it requires less hospital stay and less followup as compared to
      other surgical methods.

PMID- 23120665
TI  - Benign tumors of the larynx: a clinical study of 50 cases.
AB  - OBJECTIVE: The study was undertaken to identify the common type of lesions, and
      the age, sex distribution, symptomatology, sites of involvement and prognosis of
      the same. STUDY DESIGN: A two-year prospective study was conducted from January
      2005 to December 2006. SETTING: The study was conducted at SMS Medical College,
      Jaipur, Rajasthan, India-a tertiary referral hospital. PATIENTS: A total of 50
      patients with benign laryngeal lesions were included in the study based on
      symptoms such as hoarseness of voice, foreign body sensation, throat pain, neck
      mass and cough and with positive clinical findings on indirect laryngoscopy and
      neck examination. The patients were in the age group of 14-63 years. All
      nonoperative cases and malignant cases were excluded. Diagnostic hematological
      and radiological investigations and therapeutic microlarygoscopic procedures were
      employed. RESULTS: A male preponderance with a male:female ratio of 2.5:1 was
      observed. Majority of the patients were in the age group of 21-30 years. Vocal
      cord polyps were observed to be the commonest type of lesions. In our study,
      hoarseness of voice, cough, foreign body sensation and throat pain were found to
      be the commonest symptoms. Out of the 50 patients in the study group, only 6%
      patients got complete relief with voice rest and vocal rehabilitation; 94%
      patients required surgery, which included microlarygoscopy and endolaryngeal
      surgery. There was no recurrence in cases of vocal polyps and nodules during the
      period of observation. CONCLUSION: Microlaryngeal surgery and voice rest offer a
      cost-effective, useful and safe method for the management of benign laryngeal
      lesions. With the inclusion of lasers, they can be more precisely operated. As
      such, the standard treatment of choice in all types of benign tumors of the
      larynx should consist of a triad of approach by microlaryngeal surgery (either
      microscopic or endoscopic, with or without use of lasers), voice rest and vocal
      rehabilitation.

PMID- 23120666
TI  - Peroral fine needle aspiration cytology of parapharyngeal tumors: a study of 67
      cases.
AB  - Peroral fine needle aspiration cytology (FNAC) was carried out to diagnose
      parapharyngeal tumors in 67 patients from January 2000 to January 2008. The
      inflammatory lesions were excluded in the present study. The age of patients
      ranged from 6 years to 72 years. Analysis of results showed 35 benign tumors and
      32 malignant neoplasms. Correlation with histopathology showed a diagnostic
      accuracy of 92.5% with no false positive report. No complication was encountered
      in the present study. FNAC can replace incisional biopsy which may be hazardous
      in this area. Immediate treatment can be planned based on the FNAC report. Such a
      large series of parapharyngeal tumors diagnosed by FNAC has hardly been reported
      in India.

PMID- 23120667
TI  - Management of head and neck trauma in a developing country.
AB  - PURPOSE: To investigate cases of trauma in head and neck region; to elucidate the
      characteristic problems in a developing country. DESIGN AND SETTING: Prospective
      study; 324 patients with trauma related to head and neck analysed in a tertiary
      care center from August 1999 to August 2005 RESULTS: 33.6% of patients fell in 21
      30 year age group. Road traffic accidents (41.4%) were the most common cause of
      trauma. Nasal bone fractures were the most common fractures. 72.84% presented
      with bleeding and 72.22% with pain. 92.9% had tenderness. Only 15% of the
      patients could afford a CT scan. Plain radiograph diagnosed fractures in 83.33%
      of cases. ORIF was the treatment of choice in cases of fractures of the zygoma,
      maxilla and mandible. Open reduction and internal fixation (ORIF) gave good long
      term results with satisfactory cosmosis. Most of our patients did not have any
      significant sequelae. Cerebral concussion was the most common associated injury
      (35.48%). CONCLUSION: In developing countries, one cannot follow the approaches
      used for RTAs in developed countries. Treating surgeons will have to select
      investigation tools and treatment options according to the socioeconomical and
      cultural variations, which differ from country to country, and also within
      different parts of the country.

PMID- 23120668
TI  - Elective open tracheostomy for patients under prolonged mechanical ventilation-a
      study.
AB  - OBJECTIVE: To determine the safety of elective open tracheostomy as a routine
      intensive care unit (ICU) procedure without any selection criteria, considering
      its peri- and postoperative complications. MATERIALS AND METHODS: This is a
      descriptive study conducted in two hospitals in Davangere for a period of three
      years between April 2005 and March 2008. 40 patients, both male and female, of
      all age groups who were under mechanical ventilation in whom open tracheostomy
      was performed were included in the study. All patients who recovered were
      followed-up for two months. Complications arising during this period were
      recorded in the proforma. RESULTS: Our study consisted of 40 patients comprising
      30 males and 10 females with male to female ratio of 3:1 and average age of 35
      years, all undergoing open tracheostomy for prolonged mechanical ventilation.
      Various indications for mechanical ventilation included polytrauma, head injury,
      septicemia with multiorgan failure and dengue encephalitis. The complications
      which arised during the procedure and follow-up period included cardiac arrest,
      surgical emphysema, reactionary hemorrhage, pneumothorax, tracheo-cutaneous
      fistula, tracheo-oesophageal fistula. CONCLUSION: Elective open tracheostomy
      seems to be a safe and simple procedure, when performed by experienced surgeon
      under controlled circumstances, and should be considered as an option for
      mechanically ventilated patients.

PMID- 23120669
TI  - Endoscopic laser management of bilateral abductor palsy.
AB  - OBJECTIVE: To assess the results of endoscopic laser surgery in cases of
      bilateral abductor palsy on basis of respiration, preservation of voice
      (phonation) and swallowing. METHODS: This retrospective study includes 48
      patients (34 males and 14 females) from 5 years to 68 years of age at the time of
      intervention. 41 cases were operated with subtotal arytenoidectomy and 7 with
      unilateral posterior cordectomy. 32 patients were operated with tracheostomy and
      16 with combination of intuabtion and jet ventilation. RESULTS: 29 out of 32
      tracheostomised patients were decannulated (91%). Respiration was adequate for
      daily routine activities in most of the operated patients. Phonation was normal
      to near normal in 32 cases out of the operated 34 adult patients (95%). Most of
      the patients had normal swallowing following surgery. CONCLUSION: Subtotal
      arytenoidectomy with endoscopic laser surgery in cases of bilateral abductor
      paralysis has established its place as a preferred surgical method to obtain good
      respiration, phonation and swallowing. It minimizes the surgical time, hospital
      stay and morbidity.

PMID- 23120670
TI  - Schwannoma of the hard palate.
AB  - Schwannoma or neurilemmomas are benign, slow-growing, usually solitary,
      encapsulated tumors. They originate from the schwann cells of the nerve sheath.
      Approximately 30-40% of head and neck tumors are schwannomas. Intraoral
      schwannomas constitute a mere 1%. Tongue is the commonest site of schwannomas
      intraorally. Here we report a rare case of a hard palate swelling which was
      histopathologically diagnosed as schwannoma. The lesion was completely excised
      intraorally.

PMID- 23120671
TI  - Submandibular giant sialoliths-2 case reports and review of the literature.
AB  - Sialolithiasis is one of the most common diseases of the salivary gland. The
      submandibular gland and its duct appear to be the most susceptible. However,
      giant sialoliths have rarely been reported in the literature. Two case reports of
      giant sialoliths in the submandibular duct alone are presented. In both patients,
      a transoral removal of the stone was done under local anesthesia. The stones were
      35 mm and 25 mm long, respectively. Follow-up showed asymptomatic and normal
      functioning glands. The etiology, pathogenesis and management of such giant
      sialoliths are discussed.It is interesting to note that both patients remained
      relatively asymptomatic in spite of such long-standing sialoliths. The glands
      also recovered normal function quickly following removal of stones, which is
      interesting as such longstanding stones usually produce irrereversible functional
      damage to the gland. A conservative approach to the gland will spare the patient
      the morbidity associated with gland removal.

PMID- 23120672
TI  - Lipoid proteinosis of the larynx in siblings: exploring new modalities of
      treatment.
AB  - Lipoid proteinosis is a rare autosomal recessive disease inheritance with
      deposition of hyaline-like material at cutaneous and non-cutaneous sites. This is
      a report of two siblings presenting with typical cutaneous and laryngeal
      manifestations of lipoid proteinosis since birth who were treated successfully
      with placental extract.

PMID- 23120673
TI  - Isolated intracranial metastasis from an early glottic cancer: how rare a
      presentation?
AB  - The incidence of distant metastasis with laryngeal tumors varies from 1-4% [1].
      The lungs are the most frequent site, followed by bone and liver. Intracranial
      metastases are rarely clinically diagnosed in head neck cancer patients and if
      present are mainly located in the cerebrum and cerebellum. Early stage glottic
      squamous carcinoma with subsequent distant metastasis is rare [2]. We report a
      patient with T1N0 glottic tumor who underwent a curative radiotherapy and on 3
      months follow up presented with isolated intracranial metastasis.

PMID- 23120674
TI  - Endoscopic transcanal middle ear surgery.
AB  - The advantages and limitations of the microscope have defined postauricular
      access as the surgical intervention of choice for the treatment of diseases of
      the middle ear. The wide-angle view provided by the endoscope enables transcanal
      access to the tympanic cavity, and its otherwise difficult-to-reach extensions:
      The attic, sinus tympani, facial recess, and hypotympanum. These areas are the
      primary sites of disease and surgical failure to cure. The endoscope also allows
      an all encompassing view of the three main elements in tympanoplasty surgery: The
      ear canal, tympanic membrane, and the tympanic ring. This report is a summary of
      the author's two 17 years of experience with the use of transcanal operative
      endoscopy as the primary approach to the management of middle ear disease.

PMID- 23120675
TI  - The selection and strategy in otoendoscopic myringoplasty with autogenous adipose
      tissue.
AB  - PURPOSE: To summarize the experience and explore the clinical application of
      myringoplasty with autogenous adipose tissue by endotoscope. METHODS: In this
      study, we retrospectively analyzed 56 cases (64 ears) of otoendoscopic
      myringoplasty with autogenous adipose tissue performed between January 2006 and
      April 2007. RESULT: All patients were followed up more than 6 months. The global
      closing rate was 92.19% (59 perforations among 64 total operations), 95.08%
      (diameter of perforation <=5 mm), 33.33% (>5 mm). CONCLUSION: Otoendoscopic
      myringoplasty with adipose tissue is a simple and minimally invasive technique
      for tympanic membrane perforations. With optimal choice at indication and correct
      treatment to complication, the technique will give the advantages of slighter
      trauma, simpler procedure, lower cost and reduced complication rate.

PMID- 23120676
TI  - Nausea and vomiting after ENT surgeries: A comparison between ondansetron,
      metoclopramide and small dose of propofol.
AB  - AIMS: To evaluate the antiemetic efficacy of ondansetron, metoclopramide or small
      dose of propofol following ear, nose and throat (ENT) surgery. MATERIALS AND
      METHODS: A prospective randomized study involving 60 patients, both children and
      adults undergoing elective ENT surgery under standard general anesthesia. At the
      completion of surgery the patients received either 0.1 mg/kg of ondansetron or
      0.2 mg/kg of metoclopramide or 0.5 mg/kg of propofol intravenously. The patients
      were observed for 24 hrs after operation for any occurrence of nausea and
      vomiting. RESULTS: The incidence of postoperative nausea and vomiting (PONV)
      during first 24 hrs was recorded in 20%, 70%, 50% of patients who had received
      ondansetron, metoclopr-amide or propofol respectively (p < 0.05). Fewer patients
      given ondansetron needed rescue antiemetic. The incidence of PONV was higher
      following middle year surgery. CONCLUSION: It was concluded that ondansetron was
      most effective in preventing occurrence of PONV while metoclopramide was least
      effective. Propofol was effective only in 50% of patients, thus not recommended
      for routine use.

PMID- 23120677
TI  - Myeloperoxydase activity in the pathogenesis of cholesteatoma.
AB  - OBJECTIVE: The aim of this study was to determine the effect of myeloperoxydase
      (MPO) in bone destruction in patients of chronic otitis media (COM) with
      cholesteatoma by immtino-histochemical staining and to conclude the possible
      relationship between bone destruction in patients with cholesteatoma accompanied
      with COM and MPO activity. METHODS: The study was conducted on a total number of
      81 patients where 51 of the patients were enrolled in the "patient group" and 30
      of the patients were enrolled in the "control group" whom were operated due to
      otitis media. MPO positivism was monitored when a cytoplasmic staining process
      was performed. RESULTS: Meanwhile, a significant difference is present at a
      statistically advanced level between the MPO levels of groups (p = 0.001; p <
      0.01). However, MPO activity is absent in patients included in the control group
      or it can be observed at a very slight level. A moderate level or intense level
      of activity can be observed in patients enrolled in the study group. Excluding
      the destruction at the dura, all findings related with the middle ear and the
      erosion of the mastoid cavity and MPO activity indicated a statistically
      significant difference (p < 0.05). According to the destruction at the wall of
      the dura bone, distribution of MPO activity did not display a statistically
      meaningful difference (p > 0.05). CONCLUSION: In this study, we investigated the
      relationship between MPO level and bone destruction and found a significant level
      of correlation among the fore said. A new era may be opened in the treatment of
      cholesteatoma when preoperative MPO levels are determined and adequate
      information is obtained related with bone erosion.

PMID- 23120678
TI  - Gold weights as upper eyelid implants for facial paralysis.
AB  - Facial nerve palsy results in paralysis of orbicularis oculi muscle. This results
      in symptoms of ocular irritation due to inadequate eyelid closure. The primary
      objective of the surgeon is to protect the eye, via surgical or non-surgical
      methods. Surgical methods involve tarsrrhaphy, gold weights or springs as well as
      lower lid procedures. Nine such cases where Gold Weights were implanted in the
      upper eyelid with good results, are presented.

PMID- 23120679
TI  - Visual analog scale in hearing loss.
AB  - OBJECTIVE: To determine if visual analog scale (VAS) that has been used to
      measure magnitude of internal states such as pain, mood and various functional
      capabilities can be applied for patients with hearing loss. MATERIALS AND
      METHODS: One hundred and sixty patients, aged 12-80 years with unilateral hearing
      loss were studied using a VAS (1-10) and pure tone audiometry (PTA) of responses
      to 500, 1,000 and 2,000 Hz to determine degree and type of hearing loss. The
      results of both were compared to determine if VAS can be used in measuring
      hearing loss. RESULTS: Patients with mild, moderate hearing loss correlate well
      with corresponding VAS but other degrees of hearing loss (severe and profound)
      have poor correlation. The best correlation between PTA and VAS were found in
      conductive type of hearing loss. CONCLUSION: This study suggest that there may be
      a role for VAS in mild and moderate hearing loss. This may be more applicable in
      rural setting as a screening procedure when audiometry is not available and can
      enhance clinical hearing assessment especially in mild-to-moderate conductive
      hearing loss.

PMID- 23120680
TI  - A study of electrocardiographic changes in congenital deaf school children.
AB  - BACKGROUND: There is evidence of cardiac abnormalities in congenital deaf school
      children, together called as Jervel Lange Nielsen syndrome or Long QT syndrome.
      AIM: The main aim was to study the electrocardiographic changes in congenital
      deaf children. MATERIALS AND METHODS: Fifty congenital deaf children aged 6-18
      years were selected. ECG was taken in lead II, at rest and after exercise, as
      some are known to exhibit the abnormality after exercise. The child was made to
      run on the Tread mill till exhaustion. Corrected QT interval (QTc) was Calculated
      by Bazett's formula QTc = QT/ ?R-R. ECG was also analyzed for other abnormalities
      like Twave changes, ST depression, rhythm abnormalities etc. RESULTS: Out of 50,
      2 children showed resting QTc of 0.45 sec which is diagnostically high. Mean
      value of QTc in deaf children(Cases) before exercise was 0.4111 +/- 0.0271 sec
      and in controls 0.379 +/- 0.020 sec. Mean value of QTc after exercise in
      deaf(cases) was 0.403 +/- 0.028 sec and in controls 0.376 +/- 0.021 sec. Eight
      deaf children showed ST depression and 2 biphasic T and 2 notched T waves. Thirty
      three deaf children's parents had consanguineous marriage. CONCLUSION: The
      results were explained on the basis of ion channellopathy in heart and inner ear
      which predisposes to sensorineural hearing loss and cardiac abnormality.

PMID- 23120681
TI  - Management of unresectable head and neck cancers - a retrospective analysis at a
      rural medical college of India.
AB  - OBJECTIVE: To study the natural course of disease in patients of advanced
      squamous cell carcinoma of head and neck (SCCHN) admitted in a rural tertiary
      hospital and to formulate an acceptable protocol of management and their
      prognosis. STUDY DESIGN: A 5-year retrospective analysis of patients of advanced
      SCCHN attended in the department of Radiotherapy and admitted at department of
      ENT at B. S. Medical College, Bankura, West Bengal were analyzed for the present
      study. SETTING: B. S. Medical College, Bankura at West Bengal, which is a rural
      medical college and act as tertiary referral, center for three district of West
      Bengal namely Midnapur, Purulia, Bankura, part of Burdwan and adjoining area of
      Jharkhand state. PATIENTS: We investigated 100 patients in our hospital who
      presented with advanced and in-operable stage of SCCHN. ELIGIBILITY CRITERIA:
      Biopsy proved cases of SCCHN in stage III, stage IVA and stage IVB which is
      surgically unresectable and without any past history of radiotherapy and
      chemotherapy were included in this study.  KEY DEMOGRAPHIC FEATURES: Eighty-nine
      men and 11 female with advanced SCCHN were included in this study. Their median
      age was 48 years (36-78 years) with a median weight of 44 kg and median Karnofsky
      score 70. INTERVENTIONS: Different types of palliative surgical intervention like
      Ryles' tube insertion (16%), feeding jejunostomy (11%), tracheostomy (60%) and
      arterial ligation (2%) was done to relieve the symptoms. Forty-three patients
      received chemoradiation and 22 patients received only radiotherapy. Best
      supportive care was provided to 35 patients. OUTCOME: Twenty-nine percent of
      patients had partial response in terms of disease control and none had complete
      response. CONCLUSION: Symptomatic relief of respiratory obstruction, dysphagia
      and pain constitute the mainstay of treatment in the present study. A short
      course of radiotherapy is found to be effective in control of symptoms and helps
      to improve the quality-of-life. Complete response to therapy in advanced head and
      neck squamous cell carcinoma with a poor nutritional status is very difficult to
      achieve.

PMID- 23120682
TI  - Comparative study of two cefazolin prophylactic protocols in oncologic surgery of
      the larynx: A randomized trial.
AB  - OBJECTIVE: Patients who need major head and neck surgery like laryngectomy are at
      risk of postoperative wound infection. Although the role of antibiotics in
      prophylaxis of clean contaminated head and neck surgery has been well documented,
      controversy exists in the optimal antibiotic regimen. METHODS: In two tertiary
      referral hospitals (Imam Khomeini and Amir Alam hospital), 90 patients undergoing
      laryngectomy were prospectively randomized into two groups receiving cefazolin
      perioperative prophylaxis either for 2 days or for 5 days from June 2004 to March
      2006. Then patients were blindly examined for the development of wound infection.
      RESULTS: No wound infection was detected in either group. Two (4.4%)
      mucocutaneous fistula occurred in the 2-day group, and 3 (6.7%) in the 5-day
      group. There was no statistically significant difference in the infection rate
      between two groups. CONCLUSION: We conclude that a 2-day perioperative cefazolin
      prophylaxis is equally effective as longer therapies. The increased morbidity and
      cost of the latter are in favor of the 2-day prophylactic regimen.

PMID- 23120683
TI  - Low prevalence of GJB2 mutations in non-syndromic hearing loss in Western India.
AB  - OBJECTIVES: To identify the prevalence of GJB2 (Cx 26)and GJB6 (Cx 30) mutations
      in hearing impaired individuals from Western and South India. STUDY DESIGN: Cross
      sectional study. METHODS: Families with hearing impaired individuals (prelingual,
      non-syndromic, sensori-neural hearing loss) were enrolled and genomic DNA was
      extracted. Primers were designed for amplifying the coding and non-coding exons
      including flanking splice sites of the Cx 26 gene. Probands heterozygous or
      negative for Cx 26 mutations were further analyzed for the 342Kb deletion
      encompassing D13S1830 microsatellite marker on Cx 30. RESULTS: Two hundred and
      eighty-eight patients were enrolled in the study and 116 (40.3%) were diagnosed
      to have mutations in the coding exon 2 of Cx 26 gene. Fifty-four (18.8%) probands
      were found to have mutations in both the alleles while the remaining 62 (21.5%)
      were heterozygous for Cx 26 mutations. W24X, and W77X were the common mutations
      identified. The prevalence of familial deafness was similar in both
      consanguineous and non-consanguineous families (33% and 34.9% respectively).
      Mutations in the non-coding exon 1 and intron 1 as well as the 342 kb deletion
      involving D13S1830 marker on Cx 30 were ruled out in two hundred and thirty-four
      deaf individuals carrying none or only one mutation in the exon 2 of Cx 26 gene.
      CONCLUSION: Cx30 mutations do not contribute to the autosomal recessive non
      syndromic hearing loss (NSHL) in the Indian population. Homozygous Cx26 mutations
      account only for about 1/5th (18.8%) of autosomal recessive non-syndromic hearing
      implying the need to explore other contributory loci.

PMID- 23120684
TI  - The effects of allergic rhinitis on growth, development and body mass indexes in
      school children.
AB  - OBJECTIVE: The purpose of this study is to determine the frequency of allergic
      rhinitis (AR) in children and investigate if allergenic rhinitis demonstrated any
      effects on developmental growth levels and body mass indexes (BMI) in children.
      MATERIALS AND METHODS: 651 students, between 3-15 years of age who were randomly
      selected from four elementary schools located at Kartal, Istanbul were assessed
      according to symptoms and the presence of AR by nasal examination with the aid of
      a 0 degree 2.7 mm hand rigid endoscope. Height and weight percentile values of
      students regarding growth according to age and their BMI were calculated and
      statically assessed. Results obtained are presented. RESULTS: Findings obtained
      from a questionnaire and clinical examination does not allow us to perform a
      definite differentiation regarding in school children at age 3-5. The prevalence
      of AR in girls is higher. However, there are no any significant differences
      regarding BMIs in children with or without AR (p < 0,142). But there are
      statistically significant differences regarding height and weight percentiles in
      children with and without AR. Accordingly, there was a tendency in children
      diagnosed with AR to display low values related with height and weight
      percentiles. In Pearson chi-square testing, p values of percentile values related
      with weight (p < 0,032) and p values of percentiles related with height (p <
      0,001) were determined. CONCLUSION: AR prevalence was higher in girls
      independently from BMI values. We determined a strong relationship between BMI
      values and AR dependant to age and gender.

PMID- 23120685
TI  - Isolated sphenoid sinus disease - a retrospective analysis.
AB  - OBJECTIVE: To evaluate the etiology, symptoms, signs, imaging, surgical findings
      and outcomes of isolated sphenoid sinus disease (ISSD). DESIGN: Retrospective
      study. SETTINGS: Tertiary university based referral center. MATERIALS AND
      METHODS: All 8 patients aged 17-63, managed surgically in the department of ENT
      and Head and Neck Surgery at St. John's Medical College and Hospital, Bangalore
      from 2006 to 2008 for ISSD. Demographic data, presenting signs and symptoms
      endoscopic and imaging findings, surgical management, surgical pathology and
      clinical outcomes were investigated in the above patients. RESULTS: Of the 8
      cases of ISSD, 5 were male; 3 were female, with an age range of 17-63 years. The
      most common presenting symptom was headache (7 patients [87.5%]), followed by
      nasal obstruction and recurrent URTI (5 cases [62.5%]). Imaging included CT
      and/or MRI studies in all cases. Sphenoid sinus pathology was varied and included
      5 (62.5%) inflammatory cases, 1 (11.1%) cerebrospinal fluid fistula and 2 (22.2%)
      cases of sphenoid sinus neop;asms. Of the inflammatory cases 2 (40%) had isolated
      polyps in the sphenoid sinus [sphenochoanal polyps] and 3 (60%) had fungal
      sinusitis. Treatment was surgical, endoscopic transnasal sphenoidotomy under
      general anesthesia in all 5 patients with inflammatory ISSD Two patients with
      sphenoid sinus tumors underwent endoscopic biopsy. CONCLUSION: ISSD is rare. A
      high index of suspicion is required for diagnosis, which should be an active
      process and not one of exclusion. Both diagnostic nasal endoscopy and CT imaging
      are essential for diagnosis. The direct approach to the sphenoid sinus,
      transnasal endoscopic sphenoidotomy without ethmoidectomy is safe and effective.
      With early and adequate surgery we were able to avoid the morbidity associated
      with ISSD.

PMID- 23120686
TI  - Laryngotracheal reconstruction using iliac crest graft: an institutional
      experience.
AB  - The treatment of laryngotracheal stenosis has always been a challenge for
      otolaryngologists. Results of this operation is often not very satisfactory due
      to many reasons. Often modifications of available modality of treatment are
      required to suit a particular case. Many grafts have been used in single stage
      laryngeal reconstruction with varied results. With the help of two case reports
      we would like to emphasize on the utility and advantages of iliac crest graft for
      laryngotracheal reconstruction. The procedure for these reconstructions also
      highlights the importance of proper preoperative evaluation and planning for each
      case.

PMID- 23120687
TI  - Proboscis lateralis.
AB  - Proboscis lateralis is a rare craniofacial malformation for which no
      embryological basis has been established. The condition presents with a tubular,
      nose like structure arising from the medial canthal area or orbit roof. We
      describe here such a case that was surgically treated.

PMID- 23120688
TI  - Antrolith in the maxillary sinus: an unusual complication of endoscopic sinus
      surgery.
AB  - Antrolith of the paranasal sinuses are rare entity which are usually
      asymptomatic, caused by calcification of a nidus and are detected incidentally on
      radiological examinations. We report a case which presented to us with features
      of pansinusitis six months after endoscopic sinus surgery. Radiological
      examination revealed a discrete bony density in the maxillary sinus blocking the
      ostiomeatal complex. The bony mass was removed endoscopically from the maxillary
      sinus with drainage of discharge and debris from the sinuses. Histopathological
      examination revealed an antrolith with bony nidus and calcium deposited around
      it. We present the imaging and review the present world literature on this rare
      complication of endoscopic sinus surgery.

PMID- 23120689
TI  - Rare impacted foreign bodies of larynx.
AB  - This paper presents our experience with three cases of very unusual impacted
      foreign bodies in larynx and all without any Classical signs and symptoms of
      foreign body inhalation. Review of literature reveals that these conditions are
      rare and reported infrequently. Correct diagnosis and adequate approach is
      necessary as foreign bodies that do not obstruct the airway and which are stuck
      in place may be relatively asymptomatic but could be life threatening.

PMID- 23120690
TI  - Multiple submandibular duct (Wharton's duct) calculi of unusual size and shape.
AB  - Salivary gland stones are most common in the ductal system of submandibular
      glands and are calcified. A rare case of multiple submandibular duct (Wharton's
      duct) calculi of unusual size and shape in a 42-year-old male patient, who
      presented with pain and swelling in the region of submandibular gland and hence
      reported. Sometimes a small stone comes out into the mouth on its own or with
      gentle probing. However in this case a small intra-oral procedure was needed to
      remove the stones.

PMID- 23120691
TI  - Anterior external bony ear canal bulge.
AB  - OBJECTIVE: To study the prevalence of anterior external bony ear canal bulge.
      METHODS: Hundred patients each of the sexes among three races in Malaysia were
      studied with an otoscope and microscope. RESULTS: Anterior external ear canal
      wall bulge is seen in 34% of the Malays, 32% of the Chinese and 29.5% of the
      Indians CONCLUSION: In about one third of the population in Malaysia an anterior
      canal wall bulge is seen.

PMID- 23120692
TI  - An attempt to define the type of biopsy in a sinonasal lesion showing bony
      erosion.
AB  - OBJECTIVES: To present a case of sino-nasal destructive mass initially diagnosed
      as an inflammatory lesion following punch biopsy from the lesion however the post
      surgical histopathology was diagnostic of Grade 2 angiocentric
      immunoproliferative lesion (AIL). The reasons for the initial misdiagnosis are
      analyzed. MATERIALS AND METHODS: A 76-year-old male patient presenting with
      progressive bilateral nasal obstruction for 1 year. Repeated punch biopsies from
      the mass were suggestive of an inflammatory lesion. RESULT: The patient underwent
      surgical exenteration of the mass and the final histopathology report suggested
      AIL Grade 2. The patient was thereafter treated with chemotherapy and
      radiotherapy. CONCLUSION: Initial superficial punch biopsies lead to incorrect
      diagnosis leading to an unnecessary surgical exenteration. The explanations for
      the initial misdiagnosis are given below and appropriate diagnostic protocols,
      mode and depth of biopsy are suggested based on the case study.

PMID- 23120693
TI  - Anterior craniofacial resection - for paranasal sinus tumors involving anterior
      skull base.
AB  - Management of anterior skull base tumors is complex due to the anatomic detail of
      the region and the variety of tumors that occur in this area. Currently, the
      "gold standard" for surgery is the anterior craniofacial approach. Craniofacial
      resection represents a major advance in the surgical treatment of tumors of the
      paranasal sinuses involving anterior skull base. It allows wide exposure of the
      complex anatomical structures at the base of skull permitting monobloc tumor
      resection. This study presents a series of 18 patients with anterior skull base
      tumors, treated by a team of head-neck surgeons and neurosurgeons. The series
      included 15 malignant tumors of the nose and paranasal sinuses and 3 extensive
      benign lesions. All tumors were resected by a combined bi-frontal craniotomy and
      rhinotomy. The skull base was closed with a pediculated pericranial flap and a
      split-thickness free skin graft underneath. There were no postoperative problems
      of wound infection, cerebrospinal fluid-leakage or meningitis. Recurrent tumor
      growth or systemic metastasis occurred in 3 out of 15 patients with malignant
      tumors, 6 months to 2 years postoperatively. Craniofacial resection was thus
      found to give excellent results with low morbidity in malignant lesions and can
      also be adapted for benign tumors of anterior skull base.

PMID- 23120694
TI  - Coblation assisted excision of lingual thyroid.
AB  - Lingual thyroid (LT) tissue is the most frequent ectopic location of the thyroid
      gland. We report 5 cases of symptomatic LT and discuss the new surgical approach.
      Transoral approach and coblation assisted excision of LT was performed.
      Postoperative follow-up for all patients was like as tonsillectomy management
      without tracheotomy. It's seem that this approach is much better than other such
      as tongue-splitting, transcervical transhyoid, pharyngotomy, with an infrahyoid
      approach, combined cervical and intraoral approach, Mandibular midline osteotomy.

PMID- 23120695
TI  - Rare tumors of sinonasal track.
AB  - OBJECTIVE: To characterize the clinical behavior of rare sinonasal malignancies.
      METHODS: Clinical data from the cases of rare sinonasal malignancies at Gujarat
      Cancer and Research Institute during 2001-2007 were extracted. Data for
      histologic type of tumor, tumor stage and survival were analyzed. RESULTS: Eighty
      nine cases of the non-squamous cell malignancy were identified. The mean patient
      age was 54 years. In this study, we found minor salivary gland tumor in 31
      patients, sarcoma in 19 patients, spindle cell carcinoma (SpCC) in 19 patients,
      undifferentiated carcinoma in 9 patients, lymphoma in 6 patients and melanoma in
      3 patients. Adenoid cystic carcinoma exhibited the best survival rate (3 years
      survival rate was 77%), whereas melanoma and undifferentiated carcinoma exhibited
      poor survivals (1 year survival was 25% and 33%, respectively and 3 years
      survival rate is 0%). CONCLUSIONS: Adenoid cystic carcinoma is the most common
      squamous cell carcinoma (SCC) of the sinonasal track. Survival for the patients
      with undifferentiated carcinoma and melanoma involving the sinonasal track is
      poor.

PMID- 23120696
TI  - Foreign bodies in ENT in a teaching hospital in Eastern India.
AB  - OBJECTIVE: To evaluate the nature, common sites, modes of presentation of various
      foreign bodies (FB) in Ear, Nose and Throat (ENT). MATERIALS AND METHODS:
      Observational retrospective study carried out at Vivekananda Institute of Medical
      Sciences, Ramakrishna Mission Seva Pratishthan. The study period was between Jan
      2006 to Jan 2007. The information obtained from the hospital record books.
      RESULTS: Four hundred and eighty-two patients presented in the Department of
      Otorhinolaryngology of Vivekananda Institute of Medical Sciences, in the study
      period with FB in their ENT. Out of 482 pts, the commonest location of FB was to
      be in throat with 302 pts (62%) followed by ear with 119 pts (25%) and nose 61
      pts (13%). Amongst the FB in throat the commonest was fish bone and the commonest
      site being tonsils. Artificial denture accounted for a significant number of 13
      (4.3%). External auditory canal was the commonest site of FB lodgment in ear
      found in 118 patients (99.16%). Nasal FB were found in 61 patients; more common
      in pediatric age group (98.36%). CONCLUSION: From this study we have found that
      FB lodgement is a very common complaint with which patients come to
      otolaryngologist. The commonest site of FB lodgement is in the throat. Most of
      the FB could be removed in emergency room (ER) with or without Local Anesthesia.

PMID- 23120697
TI  - A survey of ear, nose and throat disorders in rural India.
AB  - AIMS AND OBJECTIVES: The main aim of this survey was to assess the prevalence of
      common ear, nose and throat (ENT) disorders in the rural India. SETTING: After
      initial screening of the patients at the primary health center, a week long camp
      was organized in a district where entire population resides in the rural area and
      a complete ENT examination and investigation was done by the ENT specialists.
      MATERIALS AND METHODS: A total of 950 patients were found to be suffering from
      the ENT ailments in the total population of thirty thousands of the district
      (4.31%). Out of the total of 950 patients 36.6% of patients (n = 348) had ear
      problems, 23.57% (n = 225) had nasal problems, while 16.58% (n = 161) of patients
      were suffering from the throat disorders. Among the ear patients most common
      diagnosis was chronic suppurative otitis media (CSOM) 114 and presbyacusis 83.
      Deviated nasal septum and sinusitis was most common diagnosis in nasal symptoms
      while gastroesophageal reflux (GERD) was the commonest throat problems seen in
      this study. Eleven patients had various benign tumors of head and neck and only
      one patient was found to be having oropharyngeal malignancy. The congenital head
      and neck lesion was seen in only four patients. CONCLUSIONS: In this survey 4.31%
      of the rural population of the district were having ENT ailments. The highest
      numbers rural population (35.65%) were having ear diseases. This was primarily
      due to low socioeconomic status and lack of awareness of the population. The
      nasal problem was seen in 23.57%, while throat problem was seen in 16.58%. The
      percentage of head neck malignancy in this survey was 0.0028.

PMID- 23120698
TI  - Role of estimation of arterial blood gases in the management of stridor.
AB  - AIM: We studied the epidemiology and etiology of stridor in our patients along
      with the role of arterial blood gas (ABG) analysis in their management. We also
      reviewed their prognostic indices and the clinical outcomes. MATERIALS AND
      METHODS: It was a prospective study in a tertiary referral hospital in which 72
      patients presenting with stridor, were independently evaluated by 3 different
      clinicians and clinically classified into mild, moderate and severe. Based on ABG
      values (pH, PO2, PCO2), we defined 3 groups of patients viz, those in respiratory
      failure, impending respiratory failure and those with no evidence of failure.
      Treatment was directed at the cause of stridor. Clinical outcomes were assessed
      and results classified as resolved, improved, stable and death. RESULTS: Out of
      72 patients, kappa coefficient of agreement between the 3 observers were found to
      be 0.014, indicating poor interobserver reliability for the working clinical
      classification. However, ABG analysis indicated otherwise, with 6 patients in
      respiratory failure, 19 progressing to impending failure. Hence we complied by
      the more objective ABG analysis in planning management. Laryngomalacia in
      children and hypopharyngeal malignancies in adults were found to be the most
      common causes of stridor in our study. As compared to other conditions,
      laryngomalacia in children had a poorer outcome (p = 0.001). CONCLUSION: Early
      detection of impending respiratory failure was instrumental in achieving better
      clinical outcomes in our patients presenting with stridor. Thus we inferred that
      ABG analysis is a valuable tool in the effective management of stridor.

PMID- 23120699
TI  - Objective acoustic analysis of voice improvement after phonosurgery.
AB  - OBJECTIVE: To evaluate voice improvement after phonosurgery by objective acoustic
      analysis. MATERIAL AND METHODS: This prospective study was conducted in Maulana
      Azad Medical college New Delhi from December 2002 to 2008. In this study 100
      subjects were included comprising of all age groups and either sex. All these
      patients with organic voice disorder underwent speech analysis using VAUGMI
      speech analysis program before and after phonosurgery. RESULT: All the parameter
      of voice analysis were deranged before the treatment but after surgery all the
      parameters should improvement most significant change was seen in the jitter.
      CONCLUSION: After doing this study we found that the analysis of hoarse voice
      using various parameters of acoustic analysis like fundamental frequency,
      harmonics to noise ratio, jitter, shimmer, S/z ratio helped us in identifying the
      degree of hoarseness and the severity related to it. Some parameters like jitter
      and shimmer were able to detect the component of hoarseness in perceptually
      normal voice and thus patient was helped by doing surgery and voice therapy at
      the appropriate time.

PMID- 23120700
TI  - Ear surgery without microscope; is it possible.
AB  - Our experience of endoscope usage in otological surgery is presented. We included
      17 patients with secretory otitis media for grommet insertion, 49 cases of
      myringoplasties and 6 cases of ossiculoplasties operated between May 2005 and
      2008. All the procedures were performed through transcanal route. The success
      rate regarding perforation closure was 91.5% and average air-bone gap improved
      from 22.24-12.28 db in myringoplasty group and from 27.5-13 db in ossiculoplasty
      group. Secretory changes subsided in 16 out of 17 patients in secretory otitis
      media group. Endoscopic surgery offers many advantages over microscopic surgery
      which have been discussed.

PMID- 23120701
TI  - Survival patterns in patients with carcinoma base of tongue treated with external
      beam irradiation and salvage surgery.
AB  - OBJECTIVE: The current study was designed to assess the treatment results and
      survival in the patients with carcinoma of base of tongue that were treated with
      primary radiotherapy, radiotherapy with chemotherapy and salvage surgery when
      indicated. DESIGN: A prospective study was carried out in 78 cases of carcinoma
      of the base of tongue between 1995 and 1999. METHODS: The majority of cases
      belonged to stage IV 60/78 (76.92%) as per AJCC staging. Radiotherapy in the dose
      of 60 Gy was given primarily to the patients with stage III tongue base cancer.
      Patients with early stage IV cancer were given split course radiotherapy followed
      by assessment for surgery. For the patients with advanced stage IV disease with
      poor general condition, palliative radiotherapy of 24 Gy with or without
      palliative chemotherapy was given. 15 patients were subjected to salvage surgery
      in the form of radical neck dissection alone (8 cases), extended total
      laryngectomy with neck dissection (3 cases), extended total laryngectomy (2
      cases) and extended supraglottic laryngectomy with RND in 2 cases. RESULTS: Two
      and 5 years Kaplan - Meier actuarial survival rates were 45% and 10% respectively
      with local control rates equivalent to survival rates. All surviving patients
      maintained good function and quality-of-life with few tolerable side effects.
      CONCLUSIONS: External beam radiotherapy with salvage surgery results in
      satisfactory local and regional control in stage III and IV carcinoma base of
      tongue.

PMID- 23120702
TI  - Carcinoma buccal cavity: Late presentation and salvage, experience from a North
      Indian center.
AB  - Carcinoma buccal cavity, the most common oral cavity cancer was seen in our set
      up in more than 50% cases. Forty patients of carcinoma buccal cavity were studied
      at JN Medical College, Aligarh Muslim University, and Aligarh over a period of
      last 5 years (2003-2008). Mean age at presentation 36.5 years (30-55) years.
      Male: Female, 27:13. Most common association was with smoking and chewing tobacco
      and pan over a mean long period of 15 years (8-22 years). Most common location
      was lateral wall of buccal cavity over cheek area related to their typical
      chewing habit of keeping the tobacco over that area over a prolonged period. Most
      of them, more than 90% (36 cases) presented late involving both mucosa and skin
      and in 25% cases also involving the alveolus and mandible. Wide excision and
      modified radical neck dissection with or without mandibulectomy (marginal,
      partial or hemimandibulectomy) done in all cases. Reconstruction was done by
      pedicled pectoralis major (PM) and deltopectoral (DP), the workhorse flaps for
      head and neck reconstruction for mucosal lining and skin cover respectively in 25
      cases. Five cases needed only lining done by PM flap. Ten cases were salvaged by
      pedicled forehead flap for both lining and cover. All the cases healed properly
      with acceptable results and good functional recovery. Two cases reported
      recurrence treated with postoperative radiotherapy. Poor socioeconomic status,
      smoking and chewing habit, poor oral hygiene, malnutrition and moreover lack of
      awareness led to late presentation. However, an attempt was made for salvage at
      our center.

PMID- 23120703
TI  - Comparison of bacteriology in bilaterally discharging ears in chronic suppurative
      otitis media.
AB  - Chronic suppurative otitis media is a disease with worldwide prevalence having
      potentially serious long term effects. It is a disease well known for its
      recurrence and persistence despite treatment. A study on culture and sensitivity
      of aural discharge collected from 40 cases of bilateral chronic suppurative
      otitis media was done to compare the bacteriological profile of either ear.
      Pseudomonas aeruginosa was the major organism isolated in both ears and was
      sensitive to Amikacin and newer drugs like Gatifloxacin. It was concluded that
      the infecting organisms in case of bilateral chronic suppurative otitis media are
      remarkably similar. If adequate treatment is instituted early, it can go a long
      way in reducing the prevalence of this socially embarrassing disease.

PMID- 23120704
TI  - Safety of day-stay tonsillectomy.
AB  - SUMMARY: The appropriateness of tonsillectomy as a day case procedure is not
      universally accepted, however, the procedure has been performed in our
      institution since 1996. Our policy has been to continue this practice. To assess
      the appropriateness of this practice in our institution, a retrospective study of
      802 tonsillectomies performed over 16 months was conducted. A telephone based
      questionnaire was formed to assess safety of the procedure and to evaluate the
      experiences and attitude of the served community towards our practice. Four
      hundred and thirty-three (61.3%) patients/parents were contactable to answer the
      questionnaire. Fifty-eight percent felt that a same day discharge was favorable
      with 6% considering that an overnight stay would have been preferable, others had
      no preference. Regarding the problems at home, 76% reported no problems on the
      first night, with 3% needing medical assistance that night, half of which were
      admitted in the hospital. We conclude that with the practices in place in this
      center, our policy of aiming for same day discharge is appropriate, being safe
      and agreeable to both patients and health care providers.

PMID- 23120705
TI  - Auricular reconstruction - Our experience at marienhospital stuttgart, Germany.
AB  - The aim of the paper is to report our experience of 60 ear reconstructions to
      correct the microtia with surgical technique. Autogenous rib cartilage was used
      to reconstruct the affected ear. Cartilage resorption was found in 10% of the
      cases, distortion and fusion of pinna in 20% of the cases and infection was found
      around 8% of the cases. Most of the patients were satisfied with the final
      result.

PMID- 23120706
TI  - Foreign body in tracheobronchial tree.
AB  - Foreign body inhalation into the tracheobronchial tree can prove to be a life
      threatening unless timely intervened and appropriate steps are being taken
      towards its management [1]. A review of 32 cases was done at MP Shah Medical
      College Jamnagar over a period of 2 years. Children were most susceptible to
      aspiration of foreign bodies. All the cases were selected on the basis of
      detailed clinical history, clinical features, and radiological findings. The
      cases which had a strong index of suspicion without any positive clinical history
      were also subjected to rigid bronchoscopy under general anesthesia. Maximum
      number of cases was in the age group of 1 to 3 years (62.5%). The minimum age
      group ranging from 6 months to maximum 8 years. The time of presentation of the
      patients varied from within 24 hours to upto 6 months. Only four patients
      presented within 24 hours. The maximum presenting period was within 1 week.
      Organic foreign bodies were most common presentation (groundnut). Other foreign
      bodies were grains, seeds, ball pen cap, stones and slate pencil. Definite
      history of inhalation was available only in 19 cases with symptoms of choking,
      breathlessness, cough and recurrent upper respiratory tract infection. Right main
      bronchus was found to be most common site of impaction (52%) followed by left
      main bronchus (32%) and tracheal foreign body (16%).

PMID- 23120707
TI  - A study of surgical management of chronic suppurative otitis media with
      cholesteatoma and its outcome.
AB  - OBJECTIVE: Aim of this study is evaluation of course of improvement of surgically
      treated cases of chronic suppurative otitis media (CSOM) with cholesteatoma; it
      includes hearing status, condition of mastoid cavity, study of different, natural
      and surgical condition and recurrence of disease within the study period. DESIGN:
      It is a prospective study. SETTINGS: This study was conducted in a premiere
      government hospital in Kolkata between May 2007 to April 2008. PATIENTS: Total 40
      patients between age group of 6-70 years were included in the present study which
      includes 19 males and 21 females. INTERVENTION: Surgical interventions were done
      in all the cases. Different types of mastoidectomy with or without tympanoplasty
      was done according to extent of disease process. OUTCOME: Audiometrically
      documentable hearing improvement occurred in 35% cases (p = 14), in rest of the
      ears hearing status remained unaltered. At the end of 6 months follow up 92.5% (p
      = 14) in rest (p = 37) operated ears become completely dry. Five percent cases (p
      = 2) presented with facial paralysis; among them one patient improved completely
      and another patient improved from grade V to grade III facial paralysis. No
      patient developed any post operative intracranial complications and recurrence of
      cholesteatema not found in 6 months follow up. Meatal stenosis developed in 5%
      cases (p = 2) at the end of 6 months. CONCLUSION: Surgery is mainstay of
      treatment in CSOM with cholesteatoma. Eradication of disease, prevention of
      complication, maintenance and restoration of hearing, and giving the patient a
      non-discharging ear are main aim of treatment.

PMID- 23120708
TI  - Extended anterior nasal packing in juvenile nasopharyngeal angiofibroma.
AB  - This is the case study of 16 patients in which postoperatively after complete
      removal of tumors, the bleeding did not stop with anterior and posterior nasal
      packing. In all those cases extended anterior nasal pack was applied during the
      surgery after the complete removal of tumor and bleeding stopped effectively.

PMID- 23120709
TI  - Palatal foreign body mimicking a neoplasm.
AB  - A case of young child with a palatal foreign body presenting an unusual
      diagnostic difficulty is presented. A brief literature review is presented.

PMID- 23120710
TI  - Magnet migration in a cochlear implantee - a serendipitous diagnosis.
AB  - The successful outcome of a cochlear implant habilitation program depends upon a
      multitude of vital factors, including the avid cooperation of the cochlear
      implantee, committed participation of the parents/family members and total
      dedication of the habilitation team of implant audiologists and auditory verbal
      therapists. In a rare situation, where the implantee's performance is suboptimal
      or poor inspite of successful implantation, anxious moments engulf the parents
      and the implant team, with the morbid fear of a device failure lingering at the
      back of their minds. We report such an incident in a 13-year-old cochlear
      implantee, who was an excellent cochlear implant performer for 8 years, following
      which she had rapid deterioration of her auditory verbal skills within the next
      few weeks. The hidden etiology, was the inconspicuous migration of the internal
      magnet of the Receiver-Stimulator Coil placed in the mastoid temporal bone of her
      skull, due to unexplained reasons. We share our experience with the diagnosis and
      management of this condition and review the existing world literature on this
      rarely reported entity.

PMID- 23120711
TI  - Bilateral symptomatic petrous apex effusion.
AB  - Petrous apex effusions can present with aural fullness, hearing loss and
      dizziness. Although they can be followed-up when asymptomatic, clinical
      management of symptomatic patients is controversial. In this study, we present
      clinical and radiological findings of a 24-year-old patient with bilateral
      petrous apex effusion. She had been complaining of bilateral aural fullness and
      dizziness for 2 years. Radiological examinations revealed bilateral petrous apex
      effusion. After medical treatment, her symptoms gradually disappeared. In all
      previous published studies, unilateral petrous apex effusions were reported. To
      our best knowledge, this is the first patient with trapped fluid in bilateral
      petrous apex.

PMID- 23120712
TI  - Plexiform fibrohistiocytic tumor in the submandibular region: A rare diagnosis.
AB  - Plexiform fibrohistiocytic tumor (PFHT) is a rare mesenchymal neoplasm of
      intermediate malignancy, first reported by Enzinger and Zhang in 1988 [1]. It
      mainly affects children and young adults and preferentially involves the upper
      extremity [1, 2].We report a rare case in the submandibular region which was
      diagnosed on histopathology.

PMID- 23120713
TI  - Bilateral sudden sensorineural deafness with vertigo as the sole presenting
      symptoms of diabetes mellitus - a case report.
AB  - This Paper reports a late uncontrolled diabetic presenting to an otolaryngologist
      with sudden severe sensorineural hearing loss of immediate origin with vertigo
      and tinnitus as the symptoms. Appropriate investigative and treatment measure
      resulted in deterioration of hearing in the right ear and mild improvement of
      hearing in the left ear, with no recovery of imbalance.

PMID- 23120714
TI  - An unusual benign tumor of pinna - A case report.
AB  - A 12-year-old girl presented to us with a swelling over the lateral surface of
      the right pinna of 4 years duration. Examination revealed an irregular mass
      arising from lateral surface of the pinna obscuring the external auditory canal.
      The lesion was not ulcerated. Wide excision of mass done and sent for
      Histopathological examination which revealed Tricho folliculoma. This case is
      being reported as it is a rare skin adnexal tumor arising from an unusual site.

PMID- 23120715
TI  - Study of papillary carcinoma of thyroid with uncommon sites of metastasis.
AB  - Papillary carcinoma of thyroid (PCT) is the most common type of thyroid
      malignancy and metastasis to cervical lymph nodes is very common [1]. Blood borne
      metastases from PCT are less frequent than with the other thyroid carcinomas [2].
      Uncommon sites include lungs, bone, atrium, cerebrum, kidney, skin [3].We report
      four cases of papillary carcinoma with uncommon sites of metastasis.One showed
      tumor emboli of 2.5 cm in internal jugular vein, one had tumor deposit in
      metacarpal bone and lung, one had a subcutaneous tumor deposit and one was a
      micropapillary carcinoma with metastasis axillary nodes. All these four cases
      were classical PCT.

PMID- 23120716
TI  - Evaluation of vestibular exercises in the management of benign paroxysmal
      positional vertigo.
AB  - AIM: (1) To evaluate the role of vestibular exercises in the management of benign
      paroxysmal positional vertigo (BPPV). (2) To compare the three vestibular
      exercises (Semont's manoeuvre, Epley's manoeuvre or Brandt-Daroff exercises) in
      the treatment of BPPV. SETTINGS AND DESIGN: Prospective randomised study METHODS
      AND MATERIAL: Fourty-eight patients diagnosed as BPPV in the study period
      November 2005-2006 were included in the study. They were randomly assigned to one
      of three groups, and the corresponding manoeuvre was done on them. Follow-up were
      at 2 weeks and 3 months. RESULTS: Thirty-five of the 48 patients (72.91%)
      reported relief of symptoms at 2 weeks and no recurrence of symptoms at 3 months.
      Result was best for the group which was subjected to the Epley manoeuvre (87.5%).
      CONCLUSIONS: Performance of any of the three manoeuvres can be expected to give
      good results in the management of BPPV. The Epley manoeuvre appears to be better
      than the other two in terms of relief of symptoms and prevention of recurrence.

PMID- 23120717
TI  - Vertigo in whiplash injury: A presentation of prevalent butterfly patterns of
      caloric tests.
AB  - The most common cause of whiplash injury today is the road traffic accidents.
      These patients report to a neurotologist with complaints of long-standing
      duration including vertigo, nausea, hearing loss and tinnitus. In addition to
      neck trauma there is also intracranial trauma due to movement of the brain within
      the skull thus affecting the brainstem and the supratentorial structures. In this
      retrospective study 426 patients of whiplash injury were selected from databank
      NODEC IV of the University head centre, Wurzburg, Germany. The results of
      monaural caloric test by means of butterfly chart in all these patients were
      analysed. The authors present the most prevalent caloric butterfly patterns of
      this study and pathophysiology explaining them. The study reveals that the more
      frequent pathological patterns in this study are the central brainstem lesions.

PMID- 23120718
TI  - Balloon sinuplasty.
AB  - Balloon sinuplasty is a technique in endoscopic sinus surgery that involves
      minimally invasive procedures to dilate the obstructed or stenosed anatomical
      sinus pathways. Procedure is derived from the well-recognized techinique of
      angioplasty. This article highlights the procedural methods with review of
      literature and my personal experience in balloon sinupalsty.

PMID- 23120719
TI  - Traumatic optic neuropathy - our experience.
AB  - A great deal of controversy surrounds the physiology and management of traumatic
      optic neuropathy. Needless to say, it has formed the topic of much debate in the
      past, especially with regard to its surgical management. With the advances in
      sinus endoscopic procedures, and their extended applications to the orbit and
      optic nerve, endoscopic optic nerve decompression offers a very good chance for
      salvaging vision in patients with traumatic optic neuropathy. However, there is
      no definite protocol laid down in the world literature for this condition, owing
      partially to the fact that a majority of such cases are not amenable to surgery
      within the critical period, due to the coexisting morbidities of head injury.
      There is also much controversy regarding medical versus surgical management of
      traumatic optic neuropathy. We present here our experience with this condition,
      and outline the management protocol followed.

PMID- 23120720
TI  - Juvenile nasopharyngeal angiofibroma: current treatment modalities and future
      considerations.
AB  - Juvenile angiofibroma (JNA) is a relatively uncommon, highly vascular and benign
      tumor that presents most commonly in adolescent males. Symptoms may persist from
      months to years and often times, these tumors are asymptomatic until they
      increase and encroach on critical structures. Because of technological advances
      both in surgery and radiology, management of JNA patients has been refined. With
      the advent of more sophisticated capabilities such as CT, MRI, intensity
      modulated radiation therapy (IMRT), stereotactic guidance systems as well as
      advanced embolization techniques, these tumors can be diagnosed and managed more
      effectively.Patients with juvenile angiofibroma (JNA) are typically silent for
      years and often present with epistaxis, nasal obstruction, facial numbness,
      rhinorrhea, ear popping, sinusitis, cheek swelling, visual changes and headaches.
      In addition to these symptoms, up to one-third of patients with this condition
      may present with proptosis or other orbital involvement, which are late symptoms
      and findings.Most physicians agree that surgery is the primary treatment modality
      for the early-stage disease process. However, controversy arises regarding the
      best treatment when a patient presents with more locally advanced disease
      involving widespread cranial-based extension or intracranial involvement which
      may necessitate a combination of treatment modalities including surgery and
      postoperative radiation.With the advancement of endoscopic surgery, there have
      been a number of cases reporting the value of its use. The purpose of this
      review, however, will address not only endoscopic alternatives, but will discuss
      other treatment options as reported in the literature. Robotic surgery of the
      skull base for JNA is something to expect for the future.Finally, with the advent
      of IMRT and an image-guided robotic radiotherapy delivery system, some
      researchers speculate that this will result in less objections for radiation in
      general and certainly less reservations for the use radiotherapy in certain
      circumstances, i.e. patient refusal of surgery or extensive non-resectable or
      recurrent JNA tumors.

PMID- 23120721
TI  - Long-term results of FESS - a random survey.
AB  - Very little work has been published in literature about the long-term results of
      endoscopic sinus surgery especially with substantial numbers. A cross-sectional
      study was performed of patient satisfaction following endoscopic sinus surgery
      over a mean period of 9.8 years, of 155 patients. A variety of nasal symptoms
      were assessed and interesting data was recorded in relation to abatement of
      symptoms related to nasal and systemic allergy. Overall 94% of patients were
      satisfied with functional endoscopic sinus surgery (FESS) in relieving various
      nasal symptoms and a statistically significant number showed improvement in
      allergic symptoms. Our series has the longest follow-up with the largest patient
      group recorded in literature.

PMID- 23120722
TI  - Endoscopic endonasal medial maxillectomy: case series.
AB  - INTRODUCTION: A medial maxillectomy (MM) consists of a complete resection of the
      medial wall of the maxillary sinus. Traditionally the surgery is performed via an
      open approach. With more familiarity and expertise in endoscopic sinus surgery
      the endonasal approach is feasible. OBJECTIVE: To expose the surgical technique
      and report the results of endonasal endoscopic MM in a series of 6 consecutive
      patients. MATERIALS AND METHODS: Between August 2006 and October 2009, 6 patients
      were operated with this procedure. All were men. The mean age was 62-year-old
      (range: 43-83). In 5 cases, the surgery was performed for inverted papillomas
      confined to the maxillary sinus. In one case it was a primary surgery whereas it
      was a revision surgery for the others. The sixth patient was operated for a
      solitary extramedullary plasmocytoma inserted on the intersinonasal wall
      persistent after an external radiation therapy. RESULTS: All the patients are
      free of disease at the time of writing with a mean follow-up of 18,2 months
      (range: 9-38). This has been confirmed by a nasal endoscopy and CT scans. There
      were no major per or postoperative complications. Patients suffered from crusting
      for at least 6 months postoperatively necessitating daily nasal douches. One
      patient is still complaining of intermittent epiphora when he is exposed to wind.
      CONCLUSION: Endoscopic MM can be successfully performed for the resection of
      expanding processes involving the maxillary sinus and/or the intersinonasal wall.
      Compared to open approaches, it seems to be as effective with less postoperative
      morbidity. An important technical point is to do the anterior osteotomy in front
      of the nasolacrimal duct in order to expose the prelacrimal recess that is
      typically an area for possible recurrence. Exact determination of the tumor
      attachment during the surgery is another key point for success.

PMID- 23120723
TI  - Looking after local nasal and sinus mucosa in health, disease and after surgery.
AB  - The paper emphasises the need for looking after of nasal and sinus mucosa in
      health, disease and after nasal surgery. It is a systematic arrangement of steps
      required to restore nasal mucosa to healthy state. These steps have been arranged
      to co relate them to diseases and symptoms for symptomatic and curative
      treatment. It can rationalise the need for surgery in cases non responsive to
      maximum medical treatment. It can improve postoperative surgical results after
      functional endoscopic sinus surgery (FESS) and other endoscopic assisted
      procedures.

PMID- 23120724
TI  - Extended applications of endoscopic sinus surgery and its reference to cranial
      base and pituitary fossa.
AB  - Sinus surgery has the potential of allowing ENT surgeons to encroach the
      boundaries of our colleagues in ophthalmology and neurosurgery. The advent of
      nasal endoscope and lately powered instrumentation and computer-assisted
      navigational systems has avoided the use of the conventional and more radical
      approaches by the ENT surgeon for the treatment of inflammatory pathology or
      tumors of the orbit and skull base. As rhinologists have gained more experience
      in endoscopic surgery, more areas related to the orbit and the anterior skull
      base are accessible and surgery is safer.

PMID- 23120725
TI  - Advances in endoscopic resection of sinonasal neoplasms.
AB  - Management of sinonasal diseases has undergone significant change with the advent
      of endoscopic techniques. A wide variety of pathology can now be surgically
      managed with the use of endoscopes both within and beyond the sinonasal tract.
      Endoscopic techniques allow for excellent visualization and complete tumor
      resection with low morbidity. As experience continues to grow, endonasal
      endoscopic techniques are becoming the surgical procedures of choice for the
      management of a wide variety of benign neoplasms.

PMID- 23120726
TI  - Effect of endoscopic sinus surgery on asthmatic patients with chronic
      rhinosinusitis.
AB  - BACKGROUND: There is a growing evidence that rhinosinusitis may be associated
      with asthma as different manifestations of the same disorder. Several reports
      suggest the effectiveness of endoscopic sinus surgery (ESS) in asthmatic patients
      with chronic rhinosinusitis (CRS). Whether ESS has a positive effect on the
      clinical course of asthma still remains controversial. The aim of this study was
      to investigate the outcomes of ESS on asthma in patients with coexistent CRS.
      MATERIALS AND METHODS: We performed a study to evaluate the effectiveness of ESS
      in 70 patients of CRS with associated asthma. The study compares changes in
      symptoms, medication and objective measures like pulmonary function in patients
      with persistent bronchial asthma and CRS before and after ESS. RESULTS: Following
      ESS, there was an improvement in the mean asthma symptoms (wheeze, cough and
      shortness of breath) and asthma medication use. The number of emergency
      department visits and hospital admissions also showed a reduction postsurgery.
      Objective analysis with pulmonary function tests revealed an improvement in the
      predicted scores. Three patients with extensive polyposis showed poor improvement
      after surgery and needed revision. CONCLUSIONS: This study provides corroborative
      subjective and objective evidence that ESS is efficacious in the management of
      patients with CRS and asthma.

PMID- 23120728
TI  - Conventional dacryocystorhinostomy versus endonasal dacryocystorhinostomy-a
      comparative study.
AB  - The objective of present study was to compare the results of endonasal endoscopic
      dacryocystorhinostomy and external dacryocystorhinostomy. It was a prospective
      non-randomized study. Forty consecutive patients having complaints of watering
      with complete naso lacrimal duct obstruction were selected for the study.
      Dacryocystography was done in all the cases. Selection of type of operation was
      left to the patient's choice. All patients had preoperative counseling and both
      the procedures were explained in detail with their advantages and disadvantages.
      Twenty patients underwent endonasal dacryocystorhinostomy and twenty had external
      dacryocystorhinostomy. Silicon intubation was done in all cases of endonasal
      dacryocystorhinostomy for three months after surgery. The final follow-up was
      done at 12 months after surgery. The patency of lacrimal passage was confirmed by
      syringing and patients were questioned about their symptoms. There was no
      significant difference in the results of both surgeries. The complication rate in
      both groups was almost equal. Thus we came to the conclusion that these two
      different dacryocystorhinostomy techniques are acceptable alternatives.

PMID- 23120727
TI  - Role of measurement of nasal mucociliary clearance by saccharine test as a yard
      stick of success of functional endoscopic sinus surgery.
AB  - AIM: The present study was done to establish normal nasal mucociliary clearance
      time (NMCT) in people of our region, study variations in NMCT in patients of
      chronic rhinosinusitis, to see change in NMCT after functional endoscopic sinus
      surgery (FESS) and to see whether saccharine test can be used as a yard stick of
      success of FESS. MATERIALS AND METHODS: NMCT of 100 normal individual was
      measured twice to establish control value. Fourtythree patients of chronic
      rhinosinusitis were divided into polypoidal and non-polypoidal. Their symptom
      score, endoscopic appearance score, CT scan score and NMCT was measured
      preoperatively and postoperatively. RESULTS: NMCT in control group was 6.61 +/-
      0.84 minutes, in unilateral (u/l) polypoidal sinusitis 13.45 +/- 2.07 minutes, in
      bilateral (b/l) polypoidal sinusitis 21.31 +/- 0.76 minutes, u/l non-polypoidal
      sinusitis 9.54 +/- 1.00 minutes and in b/l non-polypoidal sinusitis 11.34 +/-
      0.93 minutes. Linear relationship was seen between preoperative NMCT and
      preoperative symptom score, endoscopic appearance score, CT scan score. NMCT
      improved significantly after FESS. CONCLUSION: NMCT measurement helps in
      selection of appropriate patients for surgery. It can be used as preoperative
      indicator of success of FESS.

PMID- 23120729
TI  - Radiological correlation between the anterior ethmoidal artery and the
      supraorbital ethmoid cell.
AB  - The anterior ethmoidal artery is an important landmark in functional endoscopic
      sinus surgery. AIMS: We undertook this study to determine the reliability of
      identification of the artery on the coronal CT scan and to determine whether a
      correlation exists between the pneumatisation of the suprabullar recess and the
      vertical distance of the artery from the base skull. MATERIALS AND METHODS: 50
      randomly selected CT scans were studied. The anterior ethmoidal artery was
      identified on each side and the vertical distance between the artery and the base
      skull was measured. The orbital beak and the superior oblique muscle were used as
      landmarks to identify the artery. The CT scans were divided into two groups based
      on whether the supraorbital cell was present or absent. These groups were each
      further subdivided into 3 groups depending on the vertical distance between the
      anterior ethmoidal artery and the base skull. RESULTS: The anterior ethmoidal
      artery was reliably identified in 97% of the cases. When the supraorbital cell
      was absent, the mean distance between the artery and the base skull was 1.5 mm;
      while when the cell was present, the mean distance was 4.86 mm. When these groups
      were evaluated for statistical significance, the p value was 0.000 (highly
      significant). CONCLUSION: The orbital beak and superior oblique muscle are
      reliable landmarks to identify the anterior ethmoidal artery. There exists a
      strong correlation between the vertical distance of the artery from the base
      skull and the presence of the supraorbital ethmoid cell.

PMID- 23120730
TI  - Craniofacial variables in subjects with and without habitual snoring: A
      cephalometric comparison.
AB  - OBJECTIVE: The aim of this case control study was to evaluate which cephalometric
      variables related to craniofacial morphology discriminate between snoring and non
      snoring or any other respiratory disease subjects. MATERIALS AND METHODS: Total
      42(21 snoring and 21 non-snoring) cephalometric measurements were determined to
      study the craniofacial morphology. Non-snoring subjects were matched to snoring
      subjects by age, sex, and body mass index. Snoring was assessed using a sleep
      behavior questionnaire administered to the patients. The cephalometric
      radiographs of the study subjects were traced by a single investigator, and 1
      angular measurement and 13 linear measurements of hard and soft tissues were
      recorded. The paired Student's t test was used to analyze the cephalometric data.
      RESULTS: Vertical position of the hyoid (MP-H) was significantly longer (P<0.05)
      in snoring subjects (23.44+/-14.892mm) than non-snoring subjects (12.89+/
      4.540mm). Anterior overbite and anterior over-jet of snoring group ((4.81+/-
      3.265 and 5.83+/-8.59) were significantly higher (P<0.05) than non-snoring group
      (0.67+/-1.441 and 0.54+/-1.138). No significant differences of the other [11]
      cephalometric variables were found within groups. CONCLUSION: Snoring subjects
      appear to present craniofacial factors that differ from those of non-snoring
      subjects, and we suggest obtaining cephalogram for diagnosis and following up of
      them.

PMID- 23120731
TI  - Endoscopic septoplasty: The open book method.
AB  - The advent of endoscopes has revolutionized rhinology and the traditional
      headlight based surgeries have largely been replaced by endoscopes. Septoplasty
      for deviated nasal septum or Sluder's neuralgia have been conventionally
      performed with the aid of headlight. This can be technically challenging as
      visualization of the nasal cavity, particularly the posterior portion is rather
      limited as the procedure is performed via the nostrils. In addition, with
      headlights for illumination, teaching this procedure can be difficult as only the
      surgeon who is wearing the headlights has direct vision of the surgical
      field.Endoscopic septoplasty is an accepted alternative to traditional headlight
      approach to septoplasty. This approach provides a direct-targeted route to the
      anatomic deformity, improved visualization, and magnification of the surgical
      field. Our experience in endoscopic septoplasty is highlighted in this paper,
      excluding septoplasties performed as part of exposure to the sinuses. We use the
      open book method that to best of our knowledge has not been described in
      literature before.

PMID- 23120732
TI  - Bilateral inverted papilloma: A report of two cases and review of the current
      literature.
AB  - Inverted papilloma is locally aggressive tumour which typically presents as a
      unilateral nasal polyp. Whilst it has a malignant potential it rarely transforms
      and in its benign form the main concern originates from its locally aggressive
      nature and substantial propensity to recur. Bilateral disease can also be due to
      inverted papilloma, sometimes due to direct extension of the tumour, but it can
      also occur as two distinct lesions. Here we report two cases of bilateral
      involvement, review the current literature and highlight some important issues on
      the management and follow-up of this well known neoplasm.

PMID- 23120733
TI  - Intra turbinate diathermy cautery V/S high frequency in inferior turbinate
      hypertrophy.
AB  - OBJECTIVE: To compare the efficacy of intraturbinate monopolar cautery, bipolar
      cautery, high frequency monopolar and high frequency bipolar cautery in inferior
      turbinate hypertrophy. STUDY DESIGN: Prospective randomized single blinded
      clinical study METHOD: The study comprised of 80 patients divided in 4 groups
      each of 20 patients who underwent monopolar cautery, Bipolar cautery, high
      frequency monopolar and bipolar intra-turbinate cautery. Patients were evaluated
      on the 7th post operative day and 1 year after the surgery & saccharine transit
      time test also performed and compared. RESULTS: Remarkable improvement was
      recorded in nasal obstruction and quality of life. The Saccharine transit time
      test showed a comparable frequency and confirmed maintenance of mucociliary
      mechanism.

PMID- 23120734
TI  - Rhinosporidiosis - a report of two cases.
AB  - Rhinosporidiosis is primarily an infection of the nose. Though occasional
      involvement of other areas in the human body has been reported, it rarely
      presents as a disseminated disease. We describe two cases of recurrent
      nasopharyngeal rhinosporidiosis, one of them with cutaneous and pulmonary
      involvement. The clinical manifestations and the management of both the cases are
      discussed.

PMID- 23120735
TI  - A forgotten foreign body in the frontal sinus.
AB  - A 46-year-old female patient presented with a discharging wound over the nasal
      bridge, near the medial end of the right eyebrow of 2 months duration. She did
      not give any history of trauma or surgery in the past. Wound exploration showed a
      glass piece in the floor of the right frontal sinus. After showing the glass
      piece, patient remembered road traffic accident she had at the age of 18 years.
      Patient was asymptomatic for 28 years.To our knowledge, this is the longest
      retained case of asymptomatic foreign body in the frontal sinus reported in the
      world literature. Case report and a review of literature concerning foreign body
      in the frontal sinus are presented.

PMID- 23120736
TI  - A rare case of congenital nasopharyngeal teratoma presenting with respiratory
      distress.
AB  - Teratomas of the head and neck are rare, benign neoplasms, usually presenting in
      the neonatal period and are often malignant with regard to their location.
      Teratomas occur with a frequency of one in 4,000 live births with head and neck
      teratomas accounting for <5% of the total. Extensive literature search has shown
      that there are only two cases congenital nasopharyngeal teratoma reported in
      India, and we report the third such case.

PMID- 23120737
TI  - Inferior Turbinate osteoma - rare cause of nasal obstruction.
AB  - Osteomas are common benign tumors of the paranasal sinus, with a predilection for
      the frontal sinus. We report a rare case of inferior turbinate osteoma in a 54
      year old lady. The osteoma was resected completely by endoscopic sinus surgery
      and the patient was relieved of symptoms.

PMID- 23120738
TI  - Basics of particle therapy II: relative biological effectiveness.
AB  - In the previous review, the physical aspect of heavy particles, with a focus on
      the carbon beam was introduced. Particle beam therapy has many potential
      advantages for cancer treatment without increasing severe side effects in normal
      tissue, these kinds of radiation have different biologic characteristics and have
      advantages over using conventional photon beam radiation during treatment. The
      relative biological effectiveness (RBE) is used for many biological, clinical
      endpoints among different radiation types and is the only convenient way to
      transfer the clinical experience in radiotherapy with photons to another type of
      radiation therapy. However, the RBE varies dependent on the energy of the beam,
      the fractionation, cell types, oxygenation status, and the biological endpoint
      studied. Thus this review describes the concerns about RBE related to particle
      beam to increase interests of the Korean radiation oncologists' society.

PMID- 23120739
TI  - Current status and trend of the publication to the SCI and SCIE journals in the
      field of radiation oncology in Korea for 30 years.
AB  - PURPOSE: We collected the data of Science Citation Index (SCI) and SCI Expended
      (SCIE) papers written by the members of the Korean Society of Radiation Oncology
      (KOSRO) to analyze the current status and the future trend. MATERIALS AND
      METHODS: We searched the database of SCIE for the period from 1981 to 2011 at the
      Web of Knowledge site. Articles, reviews or proceedings written by KOSRO members
      as the first or corresponding authors were included. Search terms were the
      following combination of subject headings: therapeut radiol, radiat oncol, Korea.
      For National Cancer Center, combined search terms such as natl canc ctr, Korea
      and the names of faculties were applied. RESULTS: The total number of SCIE papers
      was 547. Numbers of the published papers in 1995, 2000, 2005, and 2010, were
      increased continuously, which was 2, 14, 40, and 83, respectively. The average
      impact factor was 2.9. The papers were published at the 134 different journals.
      The proportion of "International Journal of Radiation Oncology Biology Physics"
      was 23.4% of all the papers. The number and proportions of papers by subject
      categories were 87 (15.9%) in biology, 73 (13.3%) in physics and 387 (70.6%) in
      clinics. The papers of the top five institutions, based on the number of
      published papers, occupied 66.3%. CONCLUSION: The number of SCIE papers is
      increasing rapidly in the field of radiation oncology in Korea. To improve the
      quality of papers, multi-institutional retrospective or prospective randomized
      studies should be done for the common cancers in Korea.

PMID- 23120740
TI  - Treatment outcome in patients with vulvar cancer: comparison of concurrent
      radiotherapy to postoperative radiotherapy.
AB  - PURPOSE: To evaluate outcome and morbidity in patients with vulvar cancer treated
      with radiotherapy, concurrent chemoradiotherapy or postoperative radiotherapy.
      MATERIALS AND METHODS: The records of 24 patients treated with radiotherapy for
      vulvar cancer between July 1993 and September 2009 were retrospectively reviewed.
      All patients received once daily 1.8-4 Gy fractions external beam radiotherapy to
      median 51.2 Gy (range, 19.8 to 81.6 Gy) on pelvis and inguinal nodes. Seven
      patients were treated with primary concurrent chemoradiotherapy, one patient was
      treated with primary radiotherapy alone, four patients received palliative
      radiotherapy, and twelve patients were treated with postoperative radiotherapy.
      RESULTS: Twenty patients were eligible for response evaluation. Response rate was
      55% (11/20). The 5-year disease free survival was 42.2% and 5-year overall
      survival was 46.2%, respectively. Fifty percent (12/24) experienced with acute
      skin complications of grade III or more during radiotherapy. Late complications
      were found in 8 patients. 50% (6/12) of patients treated with lymph node
      dissection experienced severe late complications. One patient died of sepsis from
      lymphedema. However, only 16.6% (2/12) of patients treated with primary
      radiotherapy developed late complications. CONCLUSION: Outcome of patients with
      vulvar cancer treated with radiotherapy showed relatively good local control and
      low recurrence. Severe late toxicities remained higher in patients treated with
      both node dissection and radiotherapy.

PMID- 23120741
TI  - The effect of photon energy on intensity-modulated radiation therapy (IMRT) plans
      for prostate cancer.
AB  - PURPOSE: To evaluate the effect of common three photon energies (6-MV, 10-MV, and
      15-MV) on intensity-modulated radiation therapy (IMRT) plans to treat prostate
      cancer patients. MATERIALS AND METHODS: Twenty patients with prostate cancer
      treated locally to 81.0 Gy were retrospectively studied. 6-MV, 10-MV, and 15-MV
      IMRT plans for each patient were generated using suitable planning objectives,
      dose constraints, and 8-field setting. The plans were analyzed in terms of dose
      volume histogram for the target coverage, dose conformity, organs at risk (OAR)
      sparing, and normal tissue integral dose. RESULTS: Regardless of the energies
      chosen at the plans, the target coverage, conformity, and homogeneity of the
      plans were similar. However, there was a significant dose increase in rectal wall
      and femoral heads for 6-MV compared to those for 10-MV and 15-MV. The V(20 Gy) of
      rectal wall with 6-MV, 10-MV, and 15-MV were 95.6%, 88.4%, and 89.4% while the
      mean dose to femoral heads were 31.7, 25.9, and 26.3 Gy, respectively. Integral
      doses to the normal tissues in higher energy (10-MV and 15-MV) plans were reduced
      by about 7%. Overall, integral doses in mid and low dose regions in 6-MV plans
      were increased by up to 13%. CONCLUSION: In this study, 10-MV prostate IMRT plans
      showed better OAR sparing and less integral doses than the 6-MV. The biological
      and clinical significance of this finding remains to be determined afterward,
      considering neutron dose contribution.

PMID- 23120742
TI  - Radial displacement of clinical target volume in node negative head and neck
      cancer.
AB  - PURPOSE: To evaluate the radial displacement of clinical target volume in the
      patients with node negative head and neck (H&N) cancer and to quantify the
      relative positional changes compared to that of normal healthy volunteers.
      MATERIALS AND METHODS: Three node-negative H&N cancer patients and five healthy
      volunteers were enrolled in this study. For setup accuracy, neck thermoplastic
      masks and laser alignment were used in each of the acquired computed tomography
      (CT) images. Both groups had total three sequential CT images in every two weeks.
      The lymph node (LN) level of the neck was delineated based on the Radiation
      Therapy Oncology Group (RTOG) consensus guideline by one physician. We use the
      second cervical vertebra body as a reference point to match each CT image set.
      Each of the sequential CT images and delineated neck LN levels were fused with
      the primary image, then maximal radial displacement was measured at 1.5 cm
      intervals from skull base (SB) to caudal margin of LN level V, and the volume
      differences at each node level were quantified. RESULTS: The mean radial
      displacements were 2.26 (+/-1.03) mm in the control group and 3.05 (+/-1.97) in
      the H&N cancer patients. There was a statistically significant difference between
      the groups in terms of the mean radial displacement (p = 0.03). In addition, the
      mean radial displacement increased with the distance from SB. As for the mean
      volume differences, there was no statistical significance between the two groups.
      CONCLUSION: This study suggests that a more generous radial margin should be
      applied to the lower part of the neck LN for better clinical target coverage and
      dose delivery.

PMID- 23120743
TI  - Development of the DVH management software for the biologically-guided evaluation
      of radiotherapy plan.
AB  - PURPOSE: To develop the dose volume histogram (DVH) management software which
      guides the evaluation of radiotherapy (RT) plan of a new case according to the
      biological consequences of the DVHs from the previously treated patients.
      MATERIALS AND METHODS: We determined the radiation pneumonitis (RP) as an
      biological response parameter in order to develop DVH management software. We
      retrospectively reviewed the medical records of lung cancer patients treated with
      curative 3-dimensional conformal radiation therapy (3D-CRT). The biological event
      was defined as RP of the Radiation Therapy Oncology Group (RTOG) grade III or
      more. RESULTS: The DVH management software consisted of three parts (pre-existing
      DVH database, graphical tool, and Pinnacle(3) script). The pre-existing DVH data
      were retrieved from 128 patients. RP events were tagged to the specific DVH data
      through retrospective review of patients' medical records. The graphical tool was
      developed to present the complication histogram derived from the pre-existing
      database (DVH and RP) and was implemented into the radiation treatment planning
      (RTP) system, Pinnacle(3) v8.0 (Phillips Healthcare). The software was designed
      for the pre-existing database to be updated easily by tagging the specific DVH
      data with the new incidence of RP events at the time of patients' follow-up.
      CONCLUSION: We developed the DVH management software as an effective tool to
      incorporate the phenomenological consequences derived from the pre-existing
      database in the evaluation of a new RT plan. It can be used not only for lung
      cancer patients but also for the other disease site with different toxicity
      parameters.

PMID- 23120744
TI  - Observation as a treatment strategy for advanced renal cell carcinoma-a call for
      prospective validation.

PMID- 23120746
TI  - Gold nanoparticles-based fluorescence resonance energy transfer for competitive
      immunoassay of biomolecules.
AB  - A novel platform for competitive immunoassay of biomolecules was designed based
      on fluorescence resonance energy transfer (FRET) between fluorescein
      isothiocyanate (FITC) and gold nanoparticles (AuNPs). The antigen was first
      labeled with FITC, and the FITC labeled antigen was then reacted with AuNPs
      functionalized with a relative antibody to obtain the nanometer-sized sensor. The
      FRET between FITC and AuNPs led to the fluorescent quenching of FITC. Upon the
      recognition of the target antigen, the FICT labeled antigen was released from the
      AuNPs surface because of competitive immunoreaction, the distance between the
      FITC and AuNPs increased, and the interaction between FITC and AuNPs became
      weaker, which significantly hindered the FRET and, thus, increased the
      fluorescence of FITC. The change in fluorescence intensity produced a novel
      method for detection of the target. By using immunoglobulin M (IgM) as a model
      analyte, the competitive immunoassay had a limit of detection of 42 pM. The
      present method was applied for the determination of IgM in human serum with
      satisfactory results. The proposed method exhibits several advantages such as
      high quenching efficiency and sensitivity, and good specificity toward target
      versus other analogues. Moreover, this strategy could be conveniently extended
      for the detection of other biomolecules by using the corresponding antigens and
      respective antibodies.

PMID- 23120745
TI  - Integrins and p53 pathways in glioblastoma resistance to temozolomide.
AB  - Glioblastoma is the most common malignant primary brain tumor. Surgical
      resection, postoperative radiotherapy plus concomitant and adjuvant chemotherapy
      with temozolomide (TMZ) is the standard of care for newly diagnosed glioblastoma.
      In the past decade, efforts have been made to decipher genomic and core pathway
      alterations to identify clinically relevant glioblastoma subtypes. Based on these
      studies and more academic explorations, new potential therapeutic targets were
      found and several targeting agents were developed. Such molecules should
      hopefully overcome the resistance of glioblastoma to the current therapy. One of
      the hallmarks of glioblastoma subtypes was the enrichment of extracellular
      matrix/invasion-related genes. Integrins, which are cell adhesion molecules
      important in glioma cell migration/invasion and angiogenesis were one of those
      genes. Integrins seem to be pertinent therapeutic targets and antagonists
      recently reached the clinic. Although the p53 pathway appears often altered in
      glioblastoma, conflicting results can be found in the literature about the
      clinically relevant impact of the p53 status in the resistance to TMZ. Here, we
      will summarize the current knowledge on (1) integrin expression, (2) p53 status,
      and (3) relationship between integrins and p53 to discuss their potential impact
      on the resistance of glioblastoma to temozolomide.

PMID- 23120747
TI  - Integration of multiple components in polystyrene-based microfluidic devices part
      I: fabrication and characterization.
AB  - In Part I of a two-part series, we describe a simple and inexpensive approach to
      fabricate polystyrene devices that is based upon melting polystyrene (from either
      a Petri dish or powder form) against PDMS molds or around electrode materials.
      The ability to incorporate microchannels in polystyrene and integrate the
      resulting device with standard laboratory equipment such as an optical plate
      reader for analyte readout and pipets for fluid propulsion is first described. A
      simple approach for sample and reagent delivery to the device channels using a
      standard, multi-channel micropipette and a PDMS-based injection block is
      detailed. Integration of the microfluidic device with these off-chip functions
      (sample delivery and readout) enables high-throughput screens and analyses. An
      approach to fabricate polystyrene-based devices with embedded electrodes is also
      demonstrated, thereby enabling the integration of microchip electrophoresis with
      electrochemical detection through the use of a palladium electrode (for a
      decoupler) and carbon-fiber bundle (for detection). The device was sealed against
      a PDMS-based microchannel and used for the electrophoretic separation and
      amperometric detection of dopamine, epinephrine, catechol, and 3,4
      dihydroxyphenylacetic acid. Finally, these devices were compared against PDMS
      based microchips in terms of their optical transparency and absorption of an anti
      platelet drug, clopidogrel. Part I of this series lays the foundation for Part
      II, where these devices were utilized for various on-chip cellular analysis.

PMID- 23120748
TI  - Integration of multiple components in polystyrene-based microfluidic devices part
      II: cellular analysis.
AB  - In Part II of this series describing the use of polystyrene (PS) devices for
      microfluidic-based cellular assays: various cellular types and detection
      strategies are employed to determine three fundamental assays often associated
      with cells. Specifically, using either integrated electrochemical sensing or
      optical measurements with a standard multi-well plate reader, cellular uptake,
      production, or release of important cellular analytes are determined on a PS
      based device. One experiment involved the fluorescence measurement of nitric
      oxide (NO) produced within an endothelial cell line following stimulation with
      ATP. The result was a four-fold increase in NO production (as compared to a
      control), with this receptor-based mechanism of NO production verifying the
      maintenance of cell receptors following immobilization onto the PS substrate. The
      ability to monitor cellular uptake was also demonstrated by optical determination
      of Ca(2+) into endothelial cells following stimulation with the Ca(2+) ionophore
      A20317. The result was a significant increase (42%) in the calcium uptake in the
      presence of the ionophore, as compared to a control (17%) (p < 0.05). Finally,
      the release of catecholamines from a dopaminergic cell line (PC 12 cells) was
      electrochemically monitored, with the electrodes being embedded into the PS-based
      device. The PC 12 cells had better adherence on the PS devices, as compared to
      use of PDMS. Potassium-stimulation resulted in the release of 114 +/- 11 MUM
      catecholamines, a significant increase (p < 0.05) over the release from cells
      that had been exposed to an inhibitor (reserpine, 20 +/- 2 MUM of
      catecholamines). The ability to successfully measure multiple analytes, generated
      in different means from various cells under investigation, suggests that PS may
      be a useful material for microfluidic device fabrication, especially considering
      the enhanced cell adhesion to PS, its enhanced rigidity/amenability to
      automation, and its ability to enable a wider range of analytes to be
      investigated, even analytes with a high degree of hydrophobicity.

PMID- 23120749
TI  - Real-time impedance analysis of silica nanowire toxicity on epithelial breast
      cancer cells.
AB  - Silica nanowires have great potential for usage in the development of highly
      sensitive in vivo biosensors used for biomarker monitoring. However, careful
      analysis of nanowire toxicity is required prior to placing these sensors within
      the human body. This paper describes a real-time and quantitative analysis of
      nanowire cytotoxicity using impedance spectroscopy; improving upon studies that
      have utilized traditional endpoint assays. Silica nanowires were grown using the
      vapor liquid solid (VLS) method, mixed with Dulbecco's Modified Eagle Medium
      (DMEM) and exposed to Hs578T epithelial breast cancer cells at concentrations of
      0 MUg ml(-1), 1 MUg ml(-1), 50 MUg ml(-1) and 100 MUg ml(-1). Real-time cellular
      responses to silica nanowires confirm that while not cytotoxic, silica nanowires
      at high concentrations (>=50 MUg ml(-1)) are toxic to cells, and also suggest
      that cell death is due to mechanical disturbances of high numbers of nanowires.

PMID- 23120750
TI  - Biofuel cell-based self-powered biogenerators for online continuous monitoring of
      neurochemicals in rat brain.
AB  - This study demonstrates a new electrochemical method for continuous neurochemical
      sensing with a biofuel cell-based self-powered biogenerator as the detector for
      the analysis of microdialysate continuously sampled from rat brain, with glucose
      as an example analyte. To assemble a glucose/O(2) biofuel cell that can be used
      as a self-powered biogenerator for glucose sensing, glucose dehydrogenase (GDH)
      was used as the bioanodic catalyst for the oxidation of glucose with methylene
      green (MG) adsorbed onto single-walled carbon nanotubes (SWNTs) as the
      electrocatalyst for the oxidation of dihydronicotinamide adenine dinucleotide
      (NADH). Laccase crosslinked onto SWNTs was used as the biocathodic catalyst for
      the O(2) reduction. To enable the bioanode and biocathode to work efficiently in
      their individually favorable solutions and to eliminate the interference between
      the glucose bioanode and O(2) biocathode, the biofuel cell-based biogenerator was
      built in a co-laminar microfluidic chip so that the bioanodic and biocathodic
      streams could be independently optimized to provide conditions favorable for each
      of the bioelectrodes. By using a home-made portable voltmeter to output the
      voltage generated on an external resistor, the biogenerator was used for glucose
      sensing based on a galvanic cell mechanism. In vitro experiments demonstrate
      that, under the optimized conditions, the voltage generated on an external
      resistor shows a linear relationship with the logarithmic glucose concentration
      within a concentration range of 0.2 mM to 1.0 mM. Moreover, the biogenerator
      exhibits a high stability and a good selectivity for glucose sensing. The
      validity of the biofuel cell-based self-powered biogenerator for continuous
      neurochemical sensing was illustrated by online continuous monitoring of striatum
      glucose in rat brain through the combination of in vivo microdialysis. This study
      offers a new and technically simple platform for continuously monitoring
      physiologically important species in cerebral systems.

PMID- 23120751
TI  - Electrochemiluminescent lead biosensor based on GR-5 lead-dependent DNAzyme for
      Ru(phen)3(2+) intercalation and lead recognition.
AB  - An electrochemiluminescent (ECL) lead biosensor was developed based on GR-5 lead
      dependent DNAzyme for lead recognition and intercalated ruthenium tris(1,10
      phenanthroline) (Ru(phen)(3)(2+)) as the ECL probe. The thiol-modified substrate
      was first immobilized on the surface of the gold electrode via gold-sulfur self
      assembly. Subsequently, the hybridization of DNAzyme and its substrate and the
      automatic intercalation of Ru(phen)(3)(2+) proceeded. Intercalated
      Ru(phen)(3)(2+) can transfer electrons through double-stranded DNA to the
      electrode and its electrochemiluminescence was excited with a potential step
      using tripropylamine as the coreactant. In the presence of lead, the substrate
      cleaves at the scissile ribo-adenine into two fragments. The dissociation of
      DNAzyme occurs, leading to the releasing of intercalated Ru(phen)(3)(2+)
      accompanied by a decrease in the intensity of electrochemiluminescence. A
      quantity of lead can be calculated from this decrease. The biosensor is highly
      sensitive and specific, along with an ultra-low limit of detection of 0.9 pM and
      a dynamic range from 2 to 1000 pM. It enables analysis of trace amounts of lead
      in serum samples. The combination of the intercalated-Ru(phen)(3)(2+) ECL probe
      and the cofactor-dependent DNAzyme may push the performance of cofactor-sensing
      tactics to the extreme.

PMID- 23120752
TI  - Structure-function analyses of solar fuels catalysts using in situ X-ray
      scattering.
AB  - This tutorial review illustrates opportunities for the resolution of structure
      function relationships to aid in the development of new materials for solar
      energy conversion using a combination of spectroscopy and catalysis measurements
      with X-ray scattering analyses to provide in situ structural characterization of
      solar fuels catalysts. As an example, the use of molecular cobaloxime catalysts
      in bimolecular and supramolecular photocatalysis schemes for proton reduction is
      briefly reviewed. These highlight the need to develop new modular, hierarchical,
      self-healing supramolecular architectures for solar fuels catalysis. Examples of
      the X-ray scattering structural analysis of amorphous materials in the context of
      photocatalytic function are discussed in detail.

PMID- 23120753
TI  - Bottom-up assembly of photonic crystals.
AB  - In this tutorial review we highlight fundamental aspects of the physics
      underpinning the science of photonic crystals, provide insight into building
      block assembly routes to the fabrication of different photonic crystal structures
      and compositions, discuss their properties and describe how these relate to
      function, and finally take a glimpse into future applications.

PMID- 23120754
TI  - Recent developments and applications of electron microscopy to heterogeneous
      catalysis.
AB  - Transmission electron microscopy (TEM) and scanning transmission electron
      microscopy (STEM) are popular and powerful techniques used to characterize
      heterogeneous catalysts. Rapid developments in electron microscopy--especially
      aberration correctors and in situ methods--permit remarkable capabilities for
      visualizing both morphologies and atomic and electronic structures. The purpose
      of this review is to summarize the significant developments and achievements in
      this field with particular emphasis on the characterization of catalysts. We also
      highlight the potential and limitations of the various methods, describe the need
      for synergistic and complementary tools when characterizing heterogeneous
      catalysts, and conclude with an outlook that also envisions future needs in the
      field.

PMID- 23120755
TI  - Guest Editorial: Application and development of bioinformatics.

PMID- 23120756
TI  - Anxiety and deterioration of quality of life factors associated  with recurrent
      miscarriage in an observational study.
AB  - OBJECTIVES: To examine the relationship of anxiety and quality of life and sleep
      variables to recurrent miscarriages (RMs) in patients during two stages of their
      treatment in an RM-dedicated clinic - before and after the evaluation - and
      determine what factors could aggravate anxiety and worsen global well-being
      outcomes. STUDY DESIGN: Thirty-nine women who had experienced two or more RMs
      were measured before and after their evaluation and investigation in the RM
      clinic. A battery of questionnaires including the STAI scale and various
      instruments were administered to record anxiety, mental, and physical components
      of quality of life and sleep quality. Several statistical tests including
      canonical correlation were performed. RESULTS: All the patients revealed a mild
      to moderate level of anxiety, low numbers of physical and mental health but
      reasonably normal values of the global quality of sleep. The evaluation in the RM
      clinic and investigation for possible causes accounting for RM did not
      significantly change anxiety levels. The children-to-pregnancies ratio introduced
      into the analysis proved to correlate significantly with the sleep quality and
      mental health. Summarized anxiety in a given RM woman could be predicted based on
      the set of the variables, characterizing the woman's reproductive status and her
      psychological health. CONCLUSIONS: This study establishes anxiety as a common
      response in RM patients, and suggests factors that predict it. Knowing these
      factors may help clinicians to identify more accurately those RM patients who
      would be prone to a high level of anxiety and therefore need more attention and
      reassurance.

PMID- 23120757
TI  - Guest editors' introduction to the special section on computational methods in
      systems biology.

PMID- 23120758
TI  - Neonatal outcome in infants of patients with radical vaginal  trachelectomy.
AB  - OBJECTIVE: Radical vaginal trachelectomy (RVT) as a fertility-preserving surgery
      in patients with early-stage cervical cancer is proven to be oncologically safe.
      After RVT, pregnancy rates vary between 40 % and 80 %. Outcome of infants is
      complicated by a preterm delivery rate of 30 - 50 %. We investigated pregnancy
      and neonatal outcome after RVT. METHODS: A total of 154 patients with cervical
      cancer underwent RVT between March 1995 and February 2008. Desire to conceive,
      pregnancy data, and neonatal outcome were prospectively recorded. Infants' data
      were pair-matched to data of a control group according to weeks of gestation.
      Bayley scales of infant development scores were recorded in the group of preterm
      delivered infants. RESULTS: Fifty-five women who underwent RVT gave birth to 58
      children. Twenty-five (43 %) pregnancies were complicated by preterm rupture of
      membranes. Thirty infants (52 %) were born preterm, of with 17 (29 %) were < 32
      gestational weeks (GW) and seven (12 %) were < 28 GW. There were significantly
      more premature rupture of membranes in pregnancies after RVT. Despite a higher
      occurrence of postnatal infections in newborns of mothers who underwent RVT, long
      term outcomes are not affected negatively. Regarding overall morbidity, a trend
      to fewer postnatal complications, compared with the control group, was found.
      CONCLUSION: Postnatal morbidity in infants of women who underwent RVT, based on
      trend, is decreased compared with controls. Intense medical observation and
      treatment during pregnancy, birth, and neonatal period may explain this finding.
      Neonates in the RVT group have a non-significantly elevated risk for postnatal
      infections. They do not show an additional risk due to the maternal operation.
      Their long-term postnatal outcome is not affected negatively.

PMID- 23120759
TI  - The prevalence of gestational diabetes in advanced economies.
AB  - AIMS: One of the first steps in optimizing future prevention and appropriately
      allocating resources to future diagnosis and treatment of Gestational diabetes
      (GDM) is to quantify its burden. The aim of this study was therefore to conduct a
      systematic review of current international literature on the prevalence of GDM
      with a focus on advanced economies. METHODS: Based on literature searches with
      the database "PubMed" we included studies with a publication date between 2000
      and 2011. All studies were classified independently by two authors. In accordance
      with the PRISMA Statement we identified 27 original studies. RESULTS: The
      prevalence of GDM varies substantially between populations with a range of 1.7
      11.6 %. Patient self-reports yield higher prevalence estimates than values that
      are based on medical diagnosis or clinical diagnostic tests. Prevalence seems to
      vary considerably within Europe with higher prevalence values being observed in
      Southern Europe than in Northern and Central Europe. Prevalence values from
      studies from Australia and North America were within this range. CONCLUSION: This
      review provides a comprehensive and sound summary of the current state of
      research on the prevalence of GDM in advances economies as a fi rst step in
      identifying starting points for future interventions.

PMID- 23120760
TI  - Abstracts of the 33rd Annual Scientific Meeting of the American Urogynecologic
      Society. October 3-6, 2012. Chicago, Illinois, USA.

PMID- 23120761
TI  - Manual neonatal ventilation training: a respiratory function  monitor helps to
      reduce peak inspiratory pressures and tidal  volumes during resuscitation.
AB  - BACKGROUND: Neonatal resuscitation training is considered to be multifarious and
      includes manual ventilation as an essential competence for any health-care
      provider. Usually, ventilation is applied with self-inflating bags (SIBs). These
      devices have been shown to produce highly variable, operator-dependent peak
      inspiratory pressures (PIPs) and tidal volumes (V(T)). Excessive PIP and V(T)
      contribute to lung injury. We studied a simple tool to improve resuscitation
      skills. OBJECTIVE: The objectives of this study were to train healthcare
      providers to avoid excessive PIP and V(T) by visualizing these values by using a
      respiratory function monitor (RFM) and to study the sustainability of such a
      training. MATERIAL AND METHODS: Previously untrained medical professionals were
      educated and trained to ventilate a neonatal preterm manikin. PIP and V(T) were
      measured with an RFM. Graphical representations of the measurements were
      displayed during training, but the RFM was blinded during subsequent recordings.
      Participants were reassessed directly after training and 1 month later. RESULTS:
      In total, 37 participants were trained and assessed three times during the study.
      Median PIPs (range) were 32.3 (4.1 - 44) cm H(2)O before training, 17.8 (9.6 -
      23.6) cm H(2)O directly after training (P < 0.05), and 18.7 (7.5 - 41.6) cm H(2)O
      1 month later, and the values remained low, compared with before training (P <
      0.05). Median V(T)s were 6.7 (4.2 - 44) mL before training, 3.5 (1.8 - 7.3) mL
      directly after training (P < 0.05), and 4.1 (1.9 - 9.7 mL) 1 month after training
      (P < 0.05). CONCLUSION: Using a SIB, untrained staff produced excessive PIP and
      V(T). Training with a simple RFM significantly reduced the occurrence of
      excessive PIP and V(T). The effect was sustained for at least 1 month.

PMID- 23120762
TI  - Performance of the definitions of the systemic inflammatory response syndrome and
      sepsis in neonates.
AB  - AIMS: The aim of this study was to examine the applicability of the definitions
      of the systemic inflammatory response syndrome (SIRS) and sepsis to neonates
      during the first 3 days of life. METHODS: This is a retrospective study of all
      term neonates hospitalized within the first 24 h of life from 2004 to 2010 at our
      neonatal intensive care unit. RESULTS: Of 476 neonates, 30 (6 %) had a diagnosis
      of culture-proven early-onset sepsis (EOS) and 81 (17 %) had culture-negative
      clinical EOS or suspected EOS. SIRS and sepsis criteria were applied to 116 (24
      %) and 61 (13 %) neonates, respectively. Of 30 neonates with culture proven, EOS
      14 (53 %) fulfilled SIRS and sepsis criteria. The single diagnostic criterion of
      SIRS applied to 20 % (hypothermia or fever), 43 % (white blood cell
      count/immature-to-total neutrophil ratio), 87 % (respiratory symptoms), and 33 %
      (cardiocirculatory symptoms) of all neonates with culture-proven EOS.
      CONCLUSIONS: The definitions of SIRS and sepsis did not apply to about half of
      all cases of culture-proven EOS. An evidence-based approach to find the
      appropriate criteria for defining EOS in the neonate is needed.

PMID- 23120763
TI  - Unilateral hypertrophic osteoarthropathy in a patient with a vascular graft
      infection.
AB  - We report a patient who presented with high fever; a unilateral, palpable tender
      swelling along the right shin; and effusions in knee and ankle joints leading to
      the diagnosis of hypertrophic osteoarthropathy (HOA). The diagnostic workup
      revealed an infected vascular graft that had been implanted 2 years before
      because of a ruptured infrarenal aortic aneurysm as the cause of HOA. The patient
      was treated successfully with antibiotics and surgically replacing the infected
      graft. Hypertrophic osteoarthritis is a clinical entity characterized by digital
      clubbing, periostitis, and synovial effusions. Primary and secondary forms have
      been described. Secondary HOA develops as a consequence of various diseases,
      mainly intrathoracic malignancies. Vascular graft infection, as reported here, is
      a rare cause of HOA. This case underlines the typical clinical features of HOA
      and the importance of a prompt and comprehensive diagnostic workup in cases of
      HOA. Our aim is to sharpen the awareness of its multiple underlying causes.
      Unilateral HOA is a rare but strong and important sign of infection of vascular
      prosthesis.

PMID- 23120764
TI  - [HIV patients in Germany: new problems due to increased life expectancy].

PMID- 23120765
TI  - [Personality and neurobiological factors as predictors of treatment efficacy in
      patients with partial epilepsy].
AB  - In the present study, we attempted to find predictors of the response to
      antiepileptic treatment with the adjustment for individual constitutional
      characteristics of patients including the profile of hemispheric asymmetry (right
      and left handedness), premorbid personality, predisposition to affective and
      other mental disorders. We administered a large battery of tests (MMSE, HAM-A,
      HAM-D, TAS-26 and others). Treatment efficacy was assessed by the degree of
      seizure frequency reduction and remission duration. Two groups of patients, with
      100% reduction of seizures after 12 months of treatment with antiepileptic drugs
      and with the absence of reduction of seizures, were singled out. It has been
      shown that left-handedness, cognitive impairment in right-handers, alexithymia
      and affective disorders in left-handers predict poor treatment efficacy.

PMID- 23120766
TI  - [Non-convulsive status epilepticus: a clinical and instrumental diagnosis].

PMID- 23120767
TI  - [To the problem of the interrelation of migraine and epilepsy: a case analysis].

PMID- 23120768
TI  - [Clinical presentation and diagnosis of epileptic auras].
AB  - To define clinical presentations of visual auras and to reveal their clinical,
      encephalographic and neuroimaging correlates, we examined 23 patients, aged from
      5 to 25 years (mean 14+/-6 years), with focal forms of epilepsy. Patients had
      visual auras regardless of the etiology of epilepsy which developed immediately
      before epileptic seizures or were isolated. Patients had simple or complex visual
      hallucinations, the former occurring more frequently, visual illusions and ictal
      amaurosis. Positive visual phenomena were noted more frequently than negative
      ones. In most of the patients, visual hallucinations were associated with the
      pathological activity in cortical occipital regions of the brain and, in some
      cases, in temporal and parietal regions. The different pathologies (developmental
      defects, post-ischemic, atrophic and other disturbances) identified by MRI were
      found in a half of patients.

PMID- 23120769
TI  - [Association of cerebral stroke with a phosphodiesterase 4D (PDE4D) gene
      polymorphism in the Moscow population].
AB  - We studied SNP41 (rs152312) and SNP87 (rs2910829) of the PDE4D gene in 577 stroke
      patients and 270 healthy controls. The significant differences in the
      distribution of genotype and allele frequencies of the SNP41 between patients and
      controls were revealed. Genotypes AA and AG were associated with the higher risk
      of stroke in the Moscow population (OR 1,6). No association between SNP87 and
      stroke was found.

PMID- 23120770
TI  - [Comparative characteristics of clinical and pathogenetic features of first and
      recurrent cerebral stroke].
AB  - Based on the data of clinical and laboratory-instrumental study of 81 patients
      with recurrent stroke, including 63 cases after the first ischemic stroke and 18
      cases after the first hemorrhagic stroke, we compared clinical-pathogenetic
      correlations between first and recurrent strokes. A trend towards the
      localization of a focus of secondary stroke in the same hemisphere in case of the
      similar to the first stroke clinical form and in the other hemisphere in case of
      changing the clinical form (ischemic to hemorrhagic and vice versa) was found.
      Among the pathogenetic types of ischemic stroke, lacunar and hemoreologic types
      were most stable in the secondary stroke compared to the first one. In other
      variants, the pathogenesis of recurrent stroke changed more often. The authors
      concluded that further research in this direction would help to solve issues in
      prediction of secondary stroke and improvement of secondary prophylaxis.

PMID- 23120771
TI  - [Association of factors of vascular tone regulation with the development of
      hemorrhagic transformation in patients with ischemic stroke].
AB  - Concentrations of plasma vascular tone regulation markers that are indicators of
      endothelium dysfunction in the acute phase of ischemic stroke and their effect on
      the development of hemorrhagic transformation (HT) of the lesion focus have been
      studied. Concentrations of renin, endothelin 1-21, neuron-specific enolase, NT
      proCNP, soluble adhesion molecules (sICAM) were measured in 67 patients on days
      1, 3-4. Significantly higher concentrations of renin, endothelin 1-21, neuron
      specific enolase were found in patients with HT in the first day compared to
      patients without HT. The level of NT-proCNP was lower in patients with HT; the
      increase in the severity of hemorrhagic component led to the elevation of neuron
      specific enolase and sICAM concentrations. In conclusion, both markers of blood
      brain barrier damage and regulating factors of vascular tone may play a
      predictive role in the development of HT in ischemic stroke.

PMID- 23120772
TI  - [Role of semicarbazide-sensitive amine oxidase in disturbances of endogenic
      detoxication in ischemic stroke patients].
AB  - Oxidative stress is a pathogenetic factor of ischemic stroke. Enhancement in the
      activity of one of xenobiotic transformation enzymes and biogenic amines (serum
      semicarbazide-sensitive amine oxidase (SSAO)) leads to the higher production of
      secondary toxins stimulating oxidative stress. We studied 38 patients (mean age
      69,5 +/- 7,2 years) in the early restoration period of ischemic stroke. A control
      group included 17 age- and sex-matched healthy people. Severity of neurological
      and functional deficits was assessed with the NIHSS and the Barthel index,
      respectively. A number of biochemical parameters: serum SSAO activity,
      concentration of middle-sized molecules (MSM) and malonic dialdehyde (MDA) were
      measured. The higher concentration of MSM (0,80 +/- 0,22 and 0,5 +/- 0,1 g/l) and
      MDA (4,5 +/- 1,25 and 3,66 +/- 0,15 mmol/ml), respectively, was found in patients
      compared to the controls (p < 0,001). The correlative increase in MSM and MDA
      suggest the formation of chronic oxidative stress in the 4-5 months of disease.
      The changes in SSAO activity in patients with ischemic stroke that differed from
      controls were seen in 84% of cases while the increase in SSAO activity was found
      in 31% of patients. The pathogenetic link between the increase in SSAO activity
      and severity of neurological deficit was shown. This increase might be one of the
      pathogenetic links in the disturbance of neuroplasticity.

PMID- 23120773
TI  - [Cognitive disorders in the early rehabilitation period of ischemic stroke and
      possibilities of their treatment with neuromidin].
AB  - Cognitive functions were assessed in 116 patients, aged from 18 to 84 years, in
      the early rehabilitation period of the first ischemic stroke of hemispheric
      localization and in 44 patients with cerebrovascular disorders without history of
      stroke. MMSE, FAB, CDT, 5 words' test, the Schulte test, verbal fluency test, CES
      D were administered. The statistically significant decrease in cognitive
      functions was seen in the index group compared with the control one. The level of
      cognitive impairment was correlated with the severity of neurological deficit and
      age and was aggravated by depression. Neuromidin (ipidacrinum) was used in the
      treatment of 31 patients in incremental doses (intramuscular injections of 10
      mg/day during the first two weeks and later--60 mg/day during 40 days per os). As
      a result, the significant increase in cognitive function with the recovery of
      attention, memory and lobe functions was noted.

PMID- 23120774
TI  - [The antioxidant treatment of cerebral ischemic lesions].

PMID- 23120775
TI  - [The complex approach to the rehabilitation of post-stroke patients with movement
      disorders in the early rehabilitation period].
AB  - We studied 110 patients, aged 34-71 years, in the early rehabilitation period
      after stroke who were admitted to a rehabilitation neurologic department of
      Kazan. The rehabilitation approach was based on the combination of several
      methods: kinesitherapy, transcranial magnetic stimulation and cerebrolysin
      treatment. This complex reanimation allowed to achieve the marked functional
      restoration of movement abilities in many cases that was correlated with the
      normalization of brain bioelectric activity (the increase of alpha-rhythm
      spectral power, the decrease of slow-wave EEG components). The combined use of
      these three methods was more effective than a combination of any two of them.

PMID- 23120776
TI  - [The effect of stroke on health and daily activities].
AB  - The purpose of this survey was to compare quality of life between survivors of
      stroke and the general population with regard to daily activities, health and
      emotional state. We surveyed a random group of 508 Kaunas residents, aged between
      25 and 84 years, who survived the first stroke. The control group was made up of
      508 sex- and age-matched stroke-free residents of Kaunas. We used the SF-12
      quality of life questionnaire. Logistic regression was applied to evaluate the
      subjects for quality of life with regard to health, daily routine and mental
      state. Health was rated as very good by 1% of patients and 24,4% of controls (p =
      0,001) and as poor by 78,9% and 26,4%, respectively (p = 0,001). The activities
      of 35,2% of patients and 3,5% of controls were impaired by their health (p =
      0,001). State of health or emotional problems restricted social relationship in
      19,3% of patients and in 1,6% of controls (p < 0,05). Social activities were
      mostly impaired in patients after cerebral stroke (odds ratio (OR = 36,7). Stroke
      also caused depression (OR = 16) and limited domestic activities (OR = 15,5).

PMID- 23120777
TI  - [Comparative analysis of epidemiology of the first stroke: results of the
      population register, Grodno, Belarus].
AB  - A comparative analysis of incidence, mortality, case-fatality and risk-factors in
      cases of the first stroke registered during the population-based study in Grodno,
      Belarus was performed. During 2001-2003 years 2069 cases of first-ever-in-a
      lifetime stroke (FELS) were registered among 311 134 Grodno residents. The
      incidence adjusted to the WHO World standard population was 220 per 100 000
      population (95% CI, 210-231). The FELS incidence in Grodno is higher than in the
      most EU countries and is similar to that reported for Uzhgorod, Ukraine,
      Krasnoyarsk and Novosibirsk, Russia but higher than that reported from other low
      to middle income countries from all parts of the world. The 28-day case-fatality
      rate was 26,1% that is considerably higher compared to the most EU countries and
      the target level for 2015 (15%) which was set in the Helsingborg Declaration
      2006. In comparison to other 2000-2008 FELS registers, prevalence rates of
      hypertension, smoking and previous myocardial infarction in the incident-stroke
      Grodno population are the highest than other reported. The prevalence of diabetes
      mellitus and atrial fibrillation in the incident-stroke Grodno population is
      between the highest and the lowest ones reported in other studies.

PMID- 23120778
TI  - [Risk factors for stroke: data of register of a big industrial city in the West
      Siberia].

PMID- 23120779
TI  - [Influence of pineal hormone melatonin on behavioral disturbances and
      neurological status of animals after hemorrhagic stroke].
AB  - Experimental hemorrhagic stroke causes behavior and locomotor activity with
      memory impairment and neurological disturbances in rats. These shifts are weaker
      in the evening hours than after morning testing. The repeated administration of
      the pineal gland hormone melatonin (melaxen) during one week significantly
      decreases behavior and neurological deficits as well as pathomorphological signs
      in the lesion focus. The normalizing effect of the hormone is more distinct in
      the evening.

PMID- 23120780
TI  - [Acute stroke in young age (a review of international publications)].

PMID- 23120781
TI  - [A rare benign epilepsy in childhood].

PMID- 23120782
TI  - [Epilepsies with electric status epilepticus in sleep: peculiarities of clinical
      course and rational approaches to treatment].
AB  - We studied 52 patients with electric status epilepticus in slow sleep (EESSS)
      during 3-5 years. Age-dependent peculiarities of clinical course of the disease,
      risk factors for EESSS and rational approaches to antiepileptic treatment for
      these cases were singled out. Symptomatic and idiopathic EESSS variants were
      revealed. Combinations of valproates, levetiracetam and ethosuximidum were the
      most effective antiepileptic drugs in the treatment of EESSS.

PMID- 23120783
TI  - [Criptogenic epilepsy: a phenocopy of idiopathic epilepsy?].
AB  - We studied 18 patients with generalized tonic-clonic seizures. The signs of
      idiopathic epilepsy were as following: normal physical and neurological status,
      seizures of awakenings, peculiarity of circadian rhythms ("owls"), hyper
      synchronous type of EEG. The EEG and MRI study revealed insignificant
      epileptiform or structural changes. The authors consider these findings as
      possible phenocopies of idiopathic epilepsy.

PMID- 23120784
TI  - [Provoking factors for relapses in the course of epilepsy].
AB  - We studied factors causing the failure of remission and relapse of epileptic
      seizures in 24 patients who underwent clinical examination using
      electroencephalography and computed tomography (CT and MRI). There were 20,8%
      patients with idiopathic epilepsy, 33,3% with symptomatic epilepsy and 45,8% with
      cryptogenic epilepsy. The analysis of provoking factors was conducted in the
      groups of patients stratified by the number of relapses. The following factors
      were considered: iatrogenia, disturbances of routine (sleep deprivation, alcohol
      consumption, stress etc), lack of compliance, changes in the treatment regime,
      delivery in women, puberty, cranial-brain trauma. The data of their frequency in
      each group are presented.

PMID- 23120785
TI  - [Brand-name drugs and generics in the treatment of epilepsy: recommendations of
      the Russian Antiepileptic League].

PMID- 23120786
TI  - [Peculiarities of epilepsy in women with menstrual dysfunction].
AB  - An aim of the study was to optimize the diagnosis and treatment of epilepsy in
      women of reproductive age with concomitant disturbances of menstrual cycle. One
      hundred and thirty-two women, aged from 18 to 35 years, were studied. Menstrual
      dysfunction was found in 47,7% (n = 63): oligomenorrhea--in 68,3% (n = 43),
      amenorrhea--in 9,5% (n = 6) and dysfunctional metrorrhagia--in 22,2% (n = 14).
      Based on the character of hormone and ovarian dysfunction, the following
      syndromes were singled out: polycystic ovaries--54% (n = 34), isolated
      hypoprogesteronemia--23,8% (n = 15), hypercorticism--14,3% (n = 9),
      hypogonadotropic hypogonadism--7,9% (n = 5). Different hormonally-active drugs
      that allowed to normalize the menstrual cycle were used, along with basic
      antiepileptic drugs, to treat these hormonal dysfunctions and improve the course
      of epilepsy.

PMID- 23120787
TI  - [Valproic acid pharmacogenetics in an individual approach to treatment of women
      of childbearing age with epilepsy].
AB  - A clinical case of the development of undesirable pharmacological phenomena in a
      woman of childbearing age with epilepsy is described. The development of
      undesirable pharmacological phenomena at reception of average therapeutic doses
      of valproic acid has been caused by the primary (idiopathic) and secondary
      (valproate-induced) infringement of a folic cycle against a combination of
      CYP2C9*3 gene polymorphism and a mutation in the MTHFR gene.

PMID- 23120788
TI  - [Lamotrigine in treatment of women with epilepsy].
AB  - The paper presents the review of literature on the age aspect of using
      lamotrigine in pubertal period, in women of reproductive age, during pregnancy
      and lactation and in climacteric period. Special attention is drawn to the low
      teratogenic potential of this drug used as a monotherapy. It has been concluded
      that lamotrigine is expedient to be used in treatment of partial and generalized
      epilepsy in women.

PMID- 23120789
TI  - [Health of children born to mothers receiving antiepileptic treatment during the
      pregnancy].

PMID- 23120790
TI  - [Stigmata of dysembryogenesis and physical development in children born to
      mothers with epilepsy].

PMID- 23120791
TI  - [Stigmatization and social adaptation of patients with epilepsy].
AB  - The results of previous studies carried out in different countries on the problem
      of stigmatization of epileptic patients indicate the deficit of knowledge about
      epilepsy, negative attitude in the society towards the possible mutual activity
      with epileptic patients, difficulty in choosing an occupation and possibilities
      of finding a job. These issues remain understudied. The extension of knowledge
      that demands additional research is needed to get a more full conception of
      acceptance of the disease by society and non-medical population.

PMID- 23120792
TI  - [Predictors of cognitive dysfunction in epilepsy].

PMID- 23120793
TI  - [Dementia in epilepsy].
AB  - We studied clinical and neuropsychological characteristics of 106 epileptic
      patients, aged 18-87 years, with dementia. Mild, moderate and severe variants of
      dementia have been singled out. The neuropsychological tests effective for
      identification and quantitative assessment of cognitive impairment in patients
      with epilepsy are suggested.

PMID- 23120794
TI  - [Encephabol in the treatment of cognitive disorders in epilepsy].
AB  - Cognitive disorders in patients with epilepsy were studied before and after the 6
      week treatment with encephabol. The data on the examination of 24 patients were
      summarized. Before the treatment, patients with epilepsy demonstrated a larger
      number of errors, lower speed of reading and worse learning of the content
      compared to the controls (18 healthy people). Encephabol was prescribed in dosage
      600 mg/day to people over 12 years of age and in dosage 300-400 mg/day to people
      younger than 12 years. The statistically significant improvement of the global
      self-rating of cognitive functions, speed of reading, decrease of errors as well
      as learning of the content were seen after the end of treatment. The improvement
      of cognitive traits was correlated with the improvement of computed EEG
      parameters (the decrease of delta power in the right temporal and frontal
      regions). Encephabol did not lead to the increase of epileptiform activity in the
      EEG. No increase in the number and severity of seizures was noted. In conclusion,
      encephabol may be used in treatment of cognitive disorders in epilepsy.

PMID- 23120795
TI  - [Phenotropil in the complex treatment of symptomatic post traumatic epilepsy].

PMID- 23120796
TI  - [The combination of alcoholism and epilepsy].

PMID- 23120797
TI  - [Epilepsy in patients with Down syndrome].

PMID- 23120798
TI  - In brief: two intranasal corticosteroid HFA aerosols for allergic rhinitis.

PMID- 23120799
TI  - A new serum test for kala-azar. 1922.

PMID- 23120800
TI  - Expanding the scope of psychiatric nursing practice: devaluing the essence of
      psychiatric nursing?
AB  - Psychiatric Nurse Practitioners are quickly becoming sought after employees,
      especially in public mental health systems where a shrinking number of
      psychiatrists necessitate alternate access to prescribers. In addition, new
      guidelines necessitate greater attention to the follow up and monitoring of the
      medical problems of psychiatric patients. These events are occurring in the midst
      of declining reimbursement and rising litigation concerns in psychiatry. At the
      same time there is an increased focus on a recovery orientation to psychiatry
      alongside the primacy of psychotropic medicine as the most cost effective
      treatment, which can become competing aims for practitioners. It is important for
      psychiatric nurses and psychiatric nurse practitioners to consider how these
      opportunities might also have a negative impact on the core foundation of
      psychiatric nursing.

PMID- 23120801
TI  - [Drug resistance of influenza viruses].

PMID- 23120802
TI  - [Molecular targeting therapy for patients with head and neck neoplasms].

PMID- 23120803
TI  - [Selection of therapy for patients with neck neoplasm].

PMID- 23120805
TI  - [Relapsing polychondritis].

PMID- 23120804
TI  - [Practice guidelines for food allergy].

PMID- 23120806
TI  - [How to prevent, slow down and treat chronic kidney disease: history and future
      outlook].

PMID- 23120807
TI  - [Relationship between nonalcoholic fatty liver disease markers and renal function
      in patients with type 1 diabetes].
AB  - OBJECTIVE: Recent evidence suggests that nonalcoholic fatty liver disease
      (NAFLD)) is associated with an increased prevalence and incidence of chronic
      kidney disease (CKD) in diabetic and nondiabetic subjects. The aim of this study
      was to explore relationship between markers of NAFLD, including concentrations of
      aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline
      phosphatase (ALK), y-glutamyltransferase (GGT), ferritin and bilirubin with renal
      parameters, including urinary albumin excretion rate (UAE), serum creatinine and
      creatinine clearance in type 1 diabetic patients. METHODS: We analyzed 353
      patients with type 1 diabetes. None of them showed signs of adrenal, thyroid,
      renal, liver or cardiovascular diseases and received drugs, apart from insulin,
      that could attenuate glucose metabolism, insulin sensitivity, renal or liver
      function. Correlations were performed to identify relationships between NAFLD
      associated markers with renal parameters. Urinary albumin concentration was
      determined by an immunoturbidimetric assay. Creatinine clearance was calculated
      from serum and urine creatinine concentrations and urine volume. RESULTS: ALT,
      ALK and bilirubin significantly correlated with UAE (r=0.12, 0.14, and -0.10,
      respectively, all p<0.05), bilirubin and ferritin with creatinine clearance
      (r=0.14, and 0.21, respectively, all p<0.05), and ferritin with serum creatinine
      (r=0.28, p<0.05). ALT, ALK, creatinine clearance and UAE significantly correlated
      with HbA1c (r=0.14, 0.19, -0.14, and 0.13, respectively, all p<0.05), ALK,
      bilirubin, ferritin, serum creatinine and creatinine clearance with waist
      circumference (r=0.10, 0.13, 0.39, 0.34, and 0.29, respectively, all p<0.05),
      ALT, ALK and creatinine clearance with triglycerides (r=0.11, 0.25, and -0.14,
      respectively, all p<0.05), ALK, creatinine clearance and UAE with C-reactive
      protein (r=0.14, -0.18, and 0.12, respectively, all p<0.05), ALK and UAE with
      white blood cell count (r=0.12, and 0.24, respectively, all p<0.05). CONCLUSIONS:
      We demonstrated that NAFLD associated markers, including ALT, ALK, bilirubin and
      ferritin are associated with renal parameters, especially UAE, in type 1 diabetic
      patients. The most plausible explanation for these findings is that the link
      between NAFLD and CKD may be represented by the shared risk factors and
      components of the metabolic syndrome. However, the published data from recent
      prospective studies suggest that NAFLD not only is a marker of CKD but also might
      play a part in the development and progression of CKD.

PMID- 23120808
TI  - [Cardiac valves calcifications in dialysis patients].
AB  - Chronic kidney disease (CKD) patients, especially those with end-stage renal
      disease (ESRD), are at much higher risk of cardiovascular disease (CVD) than the
      general population. High serum phosphorus (P) level play important role in
      pathogenesis of cardiovascular calcifications and is a frequent and important
      cardiovascular risk factor in patients with CKD. We aimed to investigate the
      association of serum levels of C-reactive protein (CRP), parathyroid hormon
      (PTH). calcium phosphorus product (CaxP) with cardiac valves calcifications (VC)
      in patients on hemodialysis (HD). We investigated for VC using colour Doppler
      echocardiography. VC were considered present if mitral annular calcifications
      and/or aortic annular calcifications were visualized. We divided patients in two
      groups. VC negative group (VC-) were patients with absence of VC. Patients with
      presence of VC were VC positive (VC+). CRP mean levels in two samples were higher
      in VC+ group than in VC- group (17.0 vs 3.4mg/L) and (17.1 vs 4.0 mg/L) p<0.0001.
      CaxP mean level in both samples was higher in VC+ group than in VC- group, 4.8 vs
      4.2 (p=0.0219) and 5.0 vs 4.3 (p=0.0078). We also made analysis of absolute
      highest levels of three samples of CRP (CRPmax) between groups. CRPmax was higher
      in VC+ group than in VC- group, 19.5 vs 9.7 mg/L, (p=0.0045). We made analysis of
      absolute higher levels of two samples of Ca x P (CaxPmax) between groups. CaxPmax
      was higher in VC+ group than in VC- group, 5.2 vs 4.4 (p=0.0014). We found
      cardiac valve calcifications in 40 percent of patients on hemodialysis. We found
      that patients with correlation between PTH level, CRP level, CaxP product and
      cardiac valve calcifications have higher serum levels of PTH and CRP. We also
      found that CaxP product is higher in patients with cardiac valve calcifications.
      We didn't find correlation between age, dialysis duration, BMI and cardiac valve
      calcifications. These findings support careful monitoring of calcium metabolisum
      in end stage renal disease to reduce valvular cacifications and the risk of
      cardiovascular disease.

PMID- 23120809
TI  - [Angiotensin-converting enyme insertion/deletion polymorphism and blood pressure
      regulation in type 2 diabetic patients].
AB  - INTRODUCTION: The renin-angiotensin system (RAS) has been shown to have important
      role in blood pressure regulation. Inconsistent results have been reported
      regarding the association of the angiotensin-converting enzyme (ACE)
      insertion/deletion (I/D) polymorphism (NCBI ref. SNP ID: rs1799752) and
      hypertension as well as a contributing factor in the development of diabetic
      nephropathy. Aim of the study was to investigate the significance of
      insertion/deletion polymorphism of angiotensin-converting enzyme as contributing
      factor to blood pressure regulation in type 2 diabetic patients with diabetic
      nephropathy and those with preserved renal function. METHODS: Genomic DNA was
      extracted from whole blood of 100 patients with diabetic nephropathy and 102
      diabetic patients with normal renal function (urinary protein excretion rate less
      than 300 mg/day and creatinin clearence level > or = 80 ml/min). Blood pressure
      measurement was done 3 times by a nurse in the supine position, in 15 minutes
      intervals. Mean arterial pressure (MAP) was calculated according to the standard
      equation- (systolic pressure + 2 x diastolic pressure)/3, for all measurements.
      Genotyping was carried out using primers and fluorescent probes in a Lyght Cycler
      System. Statistical analysis was performed using software package SPSS 16.0 (SPSS
      inc, Chicago, IL, USA). RESULTS: Genotype frequencies of the ACE I/D)
      polymorphysm were in accordance with the Hardy-Weinberg equilibrium. In all
      subjects, the frequencies of the DD. ID and II genotypes were 0.32; 0.45 and 0.23
      respectively. The allelic frequency of the D allele in nephropatby group was 0.82
      and 0.72 in the control group. The highest systolic blood pressure was in the
      subjects with DD genotype. Systolic and mean, arterial pressure were
      significantly higher in diabetic nephropathy patients compared to patients with
      preserved kidney function, only if D allele was present (systolic blood pressure:
      DD t=2,877, p=0,006; ID t=2.733, p=0,008; mean arterial pressure: DD t=2,687,
      p=0.009; ID t=2,843, p=0,006). CONCLUSIONS: Individuals with type 2 diabetes
      mellitus who carry the D allele appear to be susceptible to development of the
      end stage renal disease. D allele might be an additional risk factor for the
      uncontrolled hypertension in diabetic nephropathy patients.

PMID- 23120810
TI  - [Surgical procedure and urologic complications after 922 kidney transplantations:
      our experience].
AB  - Between January 30 1971 and January 30 2011 922 kidney transplants were performed
      at our center, 360 (39%) from living related donor and 562 (61%) from cadaver.
      During first eight years an ureteroureterostomy was routinely used. The notable
      incidence of urological complications (fistula 11%, complications of stenting
      10.7%, stenosis and lithiasis 4%) was observed after 140 transplantations.
      Majority of these complications (60%) were treated conservatively. A significant
      reduction in this incidence (P<0.001) was achieved (fistula 1,28%, complications
      of stenting 0,26%, lithiasis 0.12%) by introducing an extravesical
      ureteroneocystostomy by Lich-Gregoire. Stenosis had the highest incidence
      (4,23%). Majority of complications (76%) were treated surgically. A native ureter
      was commonly used in replacing the transplant ureter. In majority of patients an
      end-to-end pyelo(uretero)stomy was performed. Two patients were reoperated
      because of fistula, and the third had a prolonged healing. In last nine patients
      with urological complications an end-to-side pyelo(uretero)stomy was done. There
      was no urinary leakage. The safety of method results probably from an intact
      native ureter which has normal blood irrigation.

PMID- 23120811
TI  - [Non invasive evaluation of vascular calcifications in patients on hemodyalisis].
AB  - INTRODUCTION: Cardiovascular diseases are one of the main causes of morbidity and
      mortality in dialysis patients. High incidence of cardiovascular diseases in
      patients with chronic kidney disease (CKD) can not soley be explained by
      traditional risk factors. Several studies have confirmed association between
      vascular calcification and increased mortality. MATERIALS AND METHODS: This study
      included total of 44 patients on chronic hemodialysis program, 18 women and 26
      men, with average age of 50.66 +/- 11.62 years and average duration of treatment
      of 100.25=52.83 months. We analyzed socio-demographic parameters and standard
      laboratory findings. X-ray of hand and pelvis was obtained from each patient
      along with echocardiography and carotid ultrasound imaging. To estimate the level
      of vascular calcifications on the X-rays, we used the simple vascular score
      (sVC). RESULTS: Using noninvasive methods, we found vascular calcifications in 26
      (59%) patients. In 22 (45%) patients, vascular calcifications were found in X
      rays. Four (9%) patients with vascular calcifications lacked any abnormality on X
      rays but had calcified plaques on carotid arteries or hart valves. In the group
      of patients that had vascular calcifications, 3 (14%) patients had sVC score of
      2,2 (9%) had score of 3,7 (32%) had score of 4,4 (18%) had score of 6, and 6
      (27%) had sVC score of 8. Comparing the group of patients with and without
      vascular calcifications, we found statistically significant age difference
      (p<0.05) as well as difference in the duration of hemodialysis (p<0.05). There
      were no other significant differences found between the two groups. There is a
      statistically significant correlation between sVC score and level of calcium
      (p<0.09) and iPTH (p<0.05). Using regression model for increase of sVC score, we
      found significant correlation with duration of hemodialysis (p<0.05). CONCLUSION:
      Existence of vascular calcifications represents warning sign of increased
      cardiovascular risk. Simple vascular score is an easy method for assessing that
      risk. In our study, increased frequency of vascular calcifications was directly
      correlated with older age and length of hemodialysis. Standard X-rays,
      echocardiography and ultrasound imaging can be used in screening of vascular
      calcifications. Among these methods, X-ray has advantage because it is widely
      available and easy to interpret.

PMID- 23120812
TI  - [Risk for sleep apnea syndrome and excessive daily sleepiness in chronic
      hemodialysis patients].
AB  - Sleeping disorders are common among chronic hemodialysis (HD) patients and
      obstructive sleep apnea (OSA) syndrome frequency is often underestimated. AIM: fo
      examine the risk for OSA in chronic HD patients. METHOD: The study included all
      chronic HD patients in University Hospital Osijek (N=180), mean age 63 years, 92
      men. They were treated by maintenance HD for median 3 years (0-26). The patients
      fulfilled the Croatian version of STOP and Epworth Sleepiness Scale (ESS)
      questionnaires. RESULTS: According to the STOP questionnaire, 80.6% of the
      patients have the risk for OSA, with significant difference in gender
      distribution (P=0.002). 27.2% of the patients declared excessive daytime
      sleepiness. The patients at risk for OSA have significantly more expressed
      excessive daytime sleepiness in comparison with the patients without the risk
      (P=0.017). 55% of the patients were obese, without more expressed excessive
      daytime sleepiness. Mean daytime sleepiness score was 4.41. According to the ROC
      analysis, the cutoff score for the risk for OSA assessed by STOP questionnaire at
      ESS was 2, with sensitivity 71% and specificity 57,1% (AUC 0.644, P=0.003). OSA
      related risks and comorbidities were present in the forms of snoring in 43,3%,
      excessive daytime sleepiness in 77,2%. observed apnea during sleep in 6.7%,
      arterial hypertension in 90%, diabetes mellitus in 6.7%, asthma in 7.8%,
      depression in 10.6% and gastroesophageal reflux in 38% patients. DISCUSSION:
      Chronic HD patients in the University Hospital Osijek have high risk for OSA,
      with significant gender related difference more frequent in women). Epidemiologic
      studies of OSA to date showed higher prevalence in men. Increase in the global
      prevalence of obesity goes along with OSA prevalence. Our study did not find
      obesity to be a risk for OSA. Furthermore, our study showed lower value of cut
      off score in excessive daytime sleepiness as the risk for OSA according to the
      STOP questionnaire than was officially recommended for ESS. Mean daytime
      sleepiness score determined by our study of 4.41 was obviously lower than in
      several other studies on thc patients diagnosed with sleeping disorders. The
      survey performed in the Centre for Sleeping Medicine in Split proposed ethnicity,
      life habits, sociologic and cultural factors as reasons for such broad variations
      in the results of mean daytime sleepiness obtained in their and other authors'
      studies Both the STOP questionnaire and the ESS can successfully discriminate
      healthy from OSA subjects. However, STOP questionnaire showed to be better
      predictor for OSA than ESS in the Centre for Sleeping Medicine in the Split
      survey. While our study found significantly less patients with excessive daytime
      sleepiness (according to the results of ESS) than the proportion of the patients
      at risk for OSA by STOP questionnaire (with significantly higher daytime
      sleepiness in the patients at risk or OSA), polysomnography should be performed
      in the patients at risk and the results compared afterwards. Objective
      measurements are needed, but this does not change the fact that there is still a
      need for studies aimed to find clinical predictors for OSA for different
      countries with distinct life habits and different languages. Therefore,
      standardized questionnaire version is necessary. CONCLUSION: The patients on
      chronic HD in University Hospital Centre Osijek had high frequency of risk for
      sleep apnea syndrome, especially women. The risk related risks and comorbidities
      in those patients were also common. Excessive daytime sleepiness was
      significantly higher in those with risk for OSA and the risk related cut-off
      score for excessive daily sleepiness was lower than the official for ESS.
      Polysomnography should be performed in the patients at risk also to assess
      specificity of STOP and ESS questionnaires in the patients at maintenance HD.

PMID- 23120813
TI  - [N-terminal proBNP and high sensivity cardiac troponin I concentrations in
      haemodialysis patients].
AB  - Assessment of serum biomarkers that are useful in stratification of early
      mortality and cardiovascular risk is very important in the treatment of patients
      on chronic haemodialysis. This study examined the relationship between high
      sensitivity cTnI and NT-proBNP according to glomerular filtration rates and
      vascular access (native AV-fistula or permanent catheter) in patients on
      haemodialysis. Concentrations of hs-cTnI and NT-pro BNP were increased in 35% and
      100% of patients. According to their residual renal function, patients were
      divided in three groups: oligoanuric; diuresis 0.2-0.5 L/24H and diuresis 0.5 -
      1.0 L/24h. The highest concentrations of NT-proBNP were in the first group and
      the third group showed the lowest NT-proBNP levels (p<0.05). The hs-cTnI
      concentrations showed no statistically significant differences between these
      groups. Patients with fistula accesses had lower levels of hs-cTnI and NT-proBNP
      than patients with permanent catheter, but these differences were not
      statistically significant. In patients with end-stage renal disease,
      interpretation of NT-proBNP levels should take into account residual diuresis. On
      the basis of our results, we suppose that high levels of hs-cTnI should be
      interpreted only as a consequence of myocardial necrosis. However, the
      correlation between NT-proBNP and hs-cTnI values in such patients should be
      further investigated.

PMID- 23120814
TI  - [Thirty years experience of treatment with peritoneal dialysis in University
      Hospital "Sveti Duh"].
AB  - Peritoneal dialysis (PD) is a treatment for patients with severe chronic kidney
      disease (CKD) which uses the patient's peritoneum as a membrane across which
      fluids and dissolved substances are exchanged from the blood. Implementation of
      this method begun in the seventies, with approximately 7000 patients treated in
      the year 1981. That same year, we started using this method in our center and to
      date we have a total of 167 patients. Years of experience and improvement of the
      technique made this method equivalent to hemodialysis and often even a first
      method of choice when treating patients with CKD. Data from all patients treated
      in our center were prospectively collected from year 1981 to 2010. A total of 167
      patients (83 women and 84 men) between the ages 28 and 79 (median of 59) were
      treated by this method. The number of patients enrolled in the program of PD
      decreased from 64 in the first 10 year period (1981-1990) to 40 in the last 10
      year period (2001-2010). 30-year average of PD treatment was 34 months (range
      from 1 to 110 months). Average duration of treatment per patient increased during
      the years up to 42 months per patient. The most common reason for termination of
      PD treatment was fatal outcome (48%), failure of peritoneal membrane (35%) and
      kidney transplantation (2.4%). Overall rate of peritonitis during the observed
      peritonitis was 1 every 15 months of treatment. Comparing the rates of
      peritonitis between the first and the last ten year period, a significant
      decrease from 1 every 10 months to 1 every 39 months was observed. Overall share
      of patients with diabetes was 19%. The total number of diabetic patients
      increased during years according to the increasing rates of diabetic patients
      worldwide. The decrease in number of patients enrolled in the program in our
      center is probably due to further development of transplantation program and
      opening of new dialysis centers in Croatia. The decrease of the peritonitis rate
      and consequent increase of duration of PD treatment per patient is explained by
      the improvement of techniques, solutions and better education of the patients and
      medical staff. 30 years of existence the Centre enabled us to gain experience in
      treating patients with CKD. Along with experience came the improvement of quality
      of life of our patients. Our goal is to further develop PD as it is the method of
      choice in terms of better physical and psychical rehabilitation of the patient
      with CKD waiting for the transplantation treatment.

PMID- 23120815
TI  - [Treatment of renal anemia with iron in hemodialysis patients in General Hospital
      Bjelovar].
AB  - Renal anemia is caused by a lack of erythropoietin and iron, and is associated
      with increased morbidity and mortality in patients with chronic kidney disease.
      Iron deficiency is more common than previously thought. Diagnosis of absolute and
      relative iron deficiency is difficult because of the lack of an ideal diagnostic
      method. Adequate supplementation of iron in patients with renal anemia at a
      certain percentage of patients corrects anemia, while the other reduces the
      required doses of erythropoesis stimulating agents (ESAs), which can reduce
      treatment costs. In Department of Dialysis of General Hospital Bjelovar we
      carried out a retrospective study about treating renal anemia with iron during 36
      months in 67 patients on chronic hemodialysis program in a period from 2007. to
      2010. Our goal was to see if we adequately treat renal anemia with iron and to
      show the connection between the level of hemoglobin (Hb), ferritin and
      transferrin saturation (TSAT). The average value of ferritin in the 36 months
      follow-up was 196.8mcg/l, TSAT 24.16%, 107.8 g Hb/l. We conclude that the
      elevation of ferritin and TSAT correlates with the increase of Hb values in
      patients with renal anemia. Ferritin and TSAT values in our center are above the
      minimum criteria recommended by guidelines, but not within the target values for
      the treated population.

PMID- 23120816
TI  - [Treatment of renal anemia in hemodialysis patients in General Hospital Bjelovar
      from 2007 to 2010].
AB  - Renal anemia is complication of chronic kidney disease. It is caused by
      crythropoietin deficency and is associated with adverse outcomes in CKD patients.
      Renal anemia should be treated with erythropoesis-stimulating agents (ESAs),
      supplementary iron, adequate dialysis, and if necessary with red blood cells
      transfusions. The main problem of treatment is how to determine target hemoglobin
      value and keep it within the constant range. Current guidelines recommend target
      hemoglobin level 110 - 120 g/l, but optimal value need to be adjusted for every
      patient individualy keeping in mind primary kidney disease, age, gender and
      comorbidities. In Department of Dialysis of General Hospital Bjelovar we carried
      out a retrospective study about treating renal anemia in 67 patients on chronic
      hemodialysis program during 36 months in a period from 2007. til 2010. We
      monitored hemoglobin, feritin, saturation of transferin (TSAT), dose of LSE,
      number of change in dosage and number of transfusion. Mean hemoglobin level was
      107.8 g/l, feritin level 196.8 mcg/l, TSAT 24.16%, weekly dose of ESAs 5951.9 IU.
      in 53.7% patiens dose was changed 11 - 20 times during that period, and 34% of
      patiens was treated with at least 1 dose of transfusion of red blood cells. We
      conclude that better iron supplementation and moderately higher doses of FSAs
      correlate with higher hemoglobin value, and hemoglobin variations is still big
      problem in renal anemia treatment.

PMID- 23120817
TI  - [Tunneled dialysis catheters placement program in Clinical Hospital Merkur].
AB  - INTRODUCTION: Tunneled dialysis catheters are one of the methods for vascular
      access in hemodialysis patients. In the Clinical Hospital Merkur placement of
      tunneled dialysis catheters was started in 2007. The aim of this study was to
      analyze results of that program. METHODS: We analyzed survival of tunneled
      dialysis catheters placed in our Division of nephrology from January 2009. to
      April 2011. First site of choice for placement of catheter was right jugular
      vein. Catheters were placed de novo or as over the wire exchange of a previous
      catheter. Catheters were placed under fluoroscopy guidance. Survival was analyzed
      using Kaplan-Meier analysis. Difference between survivals was tested by the log
      rank test. RESULTS: 88 catheters have been placed in 70 patients. Cumulative 1-
      year catheter survival, censored for patient death was 58%. 1-year catheter
      survival analyzed by the location of placement was as follows: jugular veins 70%.
      right subclavian vein 58%, left subclavian vein 43% and femoral veins 33%. Left
      jugular vein and femoral veins had lower survival rate in comparison with jugular
      veins (p=0.057). There was no statistical difference in catheter survival with
      respect to placement de novo or after over the wire exchange (p=0,516).
      CONCLUSION: Jugular veins are best location for placement of tunneled dialysis
      catheter. There is no statistical difference of catheter survival after placement
      de novo or after over the wire exchange in the presence of previous catheter.

PMID- 23120818
TI  - [Effect of pretransplant dialysis modality on incidence of early posttransplant
      infections in kidney recipients].
AB  - INTRODUCTION: Infection is one of the main causes of patient death and graft
      failure early after kidney transplantation. Effect of pretransplant dialysis
      modality on incidence of infections after kidney transplantation still remains
      controversial. The aim of the present study was to determine the impact of pre
      transplant dialysis modality on incidence urinary tract infections (UTI) and
      sepsis in early posttransplant period in kidney transplant recipients. MATERIALS
      AND METHODS: In this case-control retrospective study a cohort of 72 kidney,
      kidney- pancreas or kidney-liver transplant recipients was included. Infection
      was defined by either clinical presentation or microbiological finding.
      Infections were categorized by localization and cause of infection. In patients
      on peritoneal dialysis peritoneal catheter was removed intraoperatively during
      transplantation. Infection rate during first three months posttransplant was
      analyzed. Difference in frequencies was calculated using nonparametric tests.
      Proportions were calculated using chi2 test. Time to first infection was analyzed
      using Kaplan-Meier survival analysis, p value < 0.05 criterion was used to decide
      statistical significance. RESULTS: The total number of infections per patient per
      day was not significantly different in peritoneal vs. hemodialysis modality
      (0,029 +/- 0.019 to 0,029 +/- 0,031, p=ns). Also, there was no significant
      difference in peritoneal vs. hemodialysis modality in the number of UTI (0.0156
      +/- 0.0144 to 0,0165 +/- 0,0125, p=ns) and sepsis (0.0018 +/- 0.0044 to 0.0026 +/
      0.0019, p=ns) during first three months posttransplant. Similarly, no difference
      was noted between the groups in the location or cause of infection. Peritonitis
      prior to transplantation was not an independent risk factor for infections
      (p=0.37). In Cox regression PD was not an independent risk factor for either
      total infections, UTI, or sepsis. CONCLUSION: This study showed that there was
      not statistically significant difference in the risk for infection in first three
      months after kidney transplantation with respect to pretransplant dialysis
      modality. PD should be the first choice for renal replacement therapy in patients
      with end stage renal disease.

PMID- 23120819
TI  - [Attitudes towards transplantation and organ donation in high school graduates of
      math gymnasium in Osijek].
AB  - OBJECTIVE: Testing attitudes and opinions ofgraduate students in Osijek towards
      organ donation and transplantation. Examinees and methods: The research included
      99 students of math gymnasium in Osijek (54 males and 45 females, mean age 18
      years). They fulfilled an anonymous questionnaire, consisted of 24 questions
      about transplantation, willingness to donate organs, consciousness of importance
      of donating organs and attitudes of religion towards organ donation. Statistical
      analysis was made by SPSS 16.0 computer program using Chi-square test. RESULTS:
      Most of the gymnasium students (80.8%) have already heard about organ donation,
      76.8% of them have received information by television. 59.4% students know how a
      transplantation is being performed, but the majority (64.6%) of them don't know
      whom to address to receive additional information about organ donation. 27.3%
      students have discussed transplantation inside their families and 17.2% examinees
      know someone who signed the donor card. 55.6% examinees are convinced that
      transplantation procedure is safe and efficient. 41.4% thinks that family should
      give permission for explantation of a deceased patient's organs, while 33.3%
      consider it not necessary. Regarding the question whether examinees think that
      organ transplantation was a mutilation, 91.9% of them answered "no". Although
      55.6% students believe that doctors would put the same effort in saving patients,
      independent whether they possessed donor card or not, there were 60.6% that
      thought it was possible to obtain organ in Croatia by illegal ways. Nevertheless,
      79.8% students would receive organ from a deceased person, 64.6% would donate
      organs after their death. Observing ethical and religious attitudes, 92.9% are
      sure that organ donation is a humane gesture. 82.8% examinees were believers and
      60.6% of them didn't know attitudes of their religion towards organ donation.
      Women have significantly more willingness to donate their organ to family member
      during their lives (97.8%), while 81.5% males would do the same, p=0.035. Lower
      percentage of atheists were found among women (6.7%) than in men (25.9%),
      p=0.011. 53.7% males consider their religion to be against organ donation, while
      only 17.8% females, p=0.046. CONCLUSION: High school graduates have mostly heard
      about organ transplantation (many of them by television) and the majority has
      positive attitude and are willing to donate theirs and to receive organs from
      another person. Such willingness and tendency towards organ donation should be
      taken with reserve, because it was relatively young population, without life
      experience in similar situations. Within their population, believers are
      predominating, and they often don't know whether their religion is pro organ
      donation or against it. Smaller proportion, but still the majority of the
      examinees, considers the transplantation to be a safe procedure. Women and men
      show differences regarding information, attitudes and willingness to make a
      sacrifice. Women are more willing to donate organs to a family member. Still,
      there is not enough discussion about transplantation inside each family. Rate of
      ignorance and lack of information about transplantation and organ donation,
      indicates a need for better representation of this topic in media, schools,
      religious institutions and inside family.

PMID- 23120820
TI  - [A risk factors for stroke in the patients with chronic kidney disease].
AB  - Patients with chronic kidney disease (CKD) and specially end-stage renal disease
      (ESRD) have markedly advanced vascular disease when compared to the general
      population. In particular, several authors have reported more severe
      atherosclerotic disease of the carotid arteries among ESRD patients than in
      subjects with normal renal function. This accelerated disease of the cerebral
      vasculature could increase the risk of ischemic stroke in these patients.
      Additionally, ESRD is associated with hypertension, a bleeding diathesis, and the
      routine administration of heparin during hemodialysis, which could increase the
      risk of hemorrhagic stroke. Dialytic support, including both hemodialysis (HD)
      and peritoneal dialysis, have been shown to be risk factors for stroke. No
      studies have assessed stroke risk in renal transplant recipients. Although there
      are some epidemiologic data for stroke in patients with CKD, there are fewer data
      for stroke treatment in patients with CKD. In primary and secondary prevention of
      stroke even in the CKD patients, it has been well established that improved
      outcomes occur by correcting reversible risk factors, including treating
      hypertension, secondary hyperparathyroidisam, anemia, dyslipidemia, coagulation
      abnormalities, malnutrition, inflammation, controlling diabetes, and cardiac
      disease.

PMID- 23120821
TI  - [The role of arterial hypertension in developement of chronic renal failure].
AB  - The link between the kidney and hypertension has been considered a villain-victim
      relationship because of the potential two-way causality between high blood
      pressure (BP) and chronic kidney disease (CKD). Arterial hypertension (AH) per
      se, but also together with diabetes mellitus, is the most important cause of CKD
      and end-stage renal disease (ESRD) in the developed world. Pathophysiologicaly,
      the increment in systemic BP leads to the rise in glomerular pressure. Glomerular
      hypertension results in glomerular capillary wall stretch, endothelial damage and
      a rise in protein glomerular filtration. These processes, in turn, cause changes
      of mesangial and proximal tubular cells, ultimately resulting in the replacement
      of functional by non-functional connective tissue and the development of
      fibrosis. One of the most important factors in the progression of CKD is
      activation of the renin-angiotensin system (RAS). Its effect is not only elevated
      BP, but also the promotion of cell proliferation, inflammation and matrix
      accumulation. The terms that clinicians use to identify renal damage associated
      with hypertension are nephrosclerosis, benign nephrosclerosis, hypertensive
      kidney disease, or nephroangiosclerosis. Many studies, first in experimental
      animals and later in humans, have shown that the lowering of BP (and proteinuria)
      is associated with a slower progression of CKD. It seems that angiotensin
      converting enzyme inhibitors (ACEI's) are more renoprotective than other
      antihypertensives (the protection beyond the antihypertensive effect), although
      some studies have also confirmed a comparatively beneficial effect of non
      dihydropiridine calcium channel blockers (CCBs) and angiotensin II receptor
      blockers (ARBs). Moreover, it seems that a combination of antihypertensives (e.g.
      ACEI, CCB, and ARB) has a more effective action than either of the drugs alone.
      The effects depend first on the degree of BP reduction. The strict BP control has
      been considered the basis of therapy for slowing renal deterioration.

PMID- 23120822
TI  - [How to motivate nephrologists to think more "cardiac" and cardiologists to think
      more "renal"?].
AB  - Cardiovascular diseases and cardiac complications are the major causes of death
      in patients with chronic kidney disease (CKD). Recently, even a modest degree of
      impaired kidney function (i.e. low estimated glomerular filtration rate or
      albuminuria) has been recognized as a powerful cardiovascular risk factor, with a
      predictive value comparable to that of the classical cardiovascular risk factors.
      The risk of acute myocardial infarction, angina pectoris, or pulmonary edema
      associated with left ventricular failure is as high as 10% per year, and the
      incidence of sudden cardiac death, congestive heart failure. ischemic heart
      disease, and complex ventricular arrhythmias has been reported to be 9%, 10%, 17%
      to 31%, and 18%, respectively. Recently, cardiology and nephrology experts
      proposed that evaluation of renal function should be part of the work-up of
      patients with cardiovascular disease. All patients with kidney disease should be
      screened for evidence of cardiovascular disease. Patients with CKD need to be
      managed from cardiological diseases like the other patients from general
      population (including percutaneous coronary interventions, and cardiovascular
      surgery procedures). Some risks of treatment, such as bleeding and technical
      complications, are certainly more frequent in renal patients, but, overall,
      cardiologists should treat renal patients with the same vigor as nonrenal
      patients. There is very important to exchange ideas and informations between
      cardiologists and nephrologists. It is time to make departmental barriers more
      permeable and to motivate cardiologists to think more renal' and nephrologists to
      think more "cardial".

PMID- 23120823
TI  - [Kidney issues web portal--a project proposal].
AB  - Chronic kidney disease is a serious medical condition associated with premature
      mortality, decreased quality of life and increased health care needs. The
      increasing number of patients, an increasing number of kidney decease replacement
      therapy and increased total cost of treating end-stage disease are the
      characteristics ofthis important public health problem. In order to solve this
      problem the public health approach could be to promote health as a process of
      training individuals and companies to increase control over determinants of
      health and so improve their own health. In this case public health service
      proposed project is "Kidney issues web portal," which would consist of two parts,
      a public and official. The public portion would allow the education and health
      promotion by informing the entire population, and an official one would serviced
      the health professionals with the information needed. The project would be
      implemented in a series of planned activities throughout seven months. This
      project would include physicians who participate in the treatment of persons
      suffering from kidney disease, public health professionals, representatives of
      health institutions, industry, local authorities and associations of patients as
      co-operators. The project and the financing of the project would be implemented
      in three phases (teams formation, project design and implementation phase), and
      funding would be possible from several sources. The different type of evaluation
      would be carried out in two phases, process evaluation and finished project
      evaluation.

PMID- 23120824
TI  - [The role of CT peritoneography as diagnostic tool in patient on peritoneal
      dialysis with dialysate leakage].
AB  - Peritoneal dialysis (PD) can be considered as first method for dialytic treatment
      because improved quality of life and patient survival compared to hemodialysis.
      The most frequent complications of PD are peritonitis, peritoneal catheter exit
      site infection and mechanical complications as dialysate leakage. We present a 62
      year old female patient with end-stage renal disease caused by poststreptococcal
      glomerulonephritis. One month after laparoscopic placement of peritoneal catheter
      patient started with continuous ambulatory peritoneal dialysis. Few weeks after
      starting the procedure enlargement of anterior abdominal wall close to the exit
      site of peritoneal catheter was noticed. Enlargement was disappeared after
      decreasing intraabdominal pressure with lowering volume of dialysate. Also,
      patient started with automated peritoneal dialysis (APD), but after abdominal
      straining enlargement of anterior abdominal wall was present again. Computed
      tomography of abdomen and pelvis with placement of contrast in dialysate (CT
      peritoneography) was performed. Imaging revealed dialysate leakage from
      peritoneal cavity to subcutaneous tissue. PD was temporarly stopped, peritoneal
      catheter removed and hernioplasty was made. After four weeks new peritoneal
      catheter was implanted and APD was successfully started (without dialysate
      leakage). CT peritoneography have important role as diagnostic tool for
      discovering dialysate leakage. If conservative management was unsuccessfull,
      surgical treatment is necessary.

PMID- 23120825
TI  - [Structure of the kidney glomerulus].

PMID- 23120826
TI  - [Biopsy of the kidney].

PMID- 23120827
TI  - [Types of morphological changes in the glomerulus].

PMID- 23120828
TI  - [Tubulointerstitial changes in glomerular kidney diseases].

PMID- 23120829
TI  - [Glomerular kidney diseases that are associated with a large clinical proteinuria
      and/or nephrotic syndrome].

PMID- 23120830
TI  - [Glomerular kidney disease clinically manifesting as mainly hematuria or blood in
      the urine].

PMID- 23120831
TI  - [Glomerular kidney disease that is associated with nephrotic syndrome or rapidly
      advancing renal failure].

PMID- 23120832
TI  - [Kidney changes in systemic lupus erythematosus and other autoimmune diseases].

PMID- 23120833
TI  - [Kidney changes in metabolic diseases].

PMID- 23120834
TI  - [Thrombotic microangiopathy].

PMID- 23120835
TI  - [Glomerular kidney disease in dysproteinemia and with organized deposits].

PMID- 23120836
TI  - [Importance of immunomorphologic tests in diagnosis of glomerular kidney
      diseases].

PMID- 23120837
TI  - [The importance of ultrastructural examination in diagnosis of glomerular kidney
      diseases].

PMID- 23120838
TI  - [Pathomorphologic protocol for evaluating puncture biopsy of the kidneys].

PMID- 23120839
TI  - [Diagnosis of changes in the transplanted kidney].

PMID- 23120840
TI  - [Surgical treatment of acute pancreatitis].

PMID- 23120841
TI  - [The role of nutrition support in acute pancreatitis].
AB  - Nutritional support has been recognised as an important part in the treatment of
      acute pancreatitis. Acute pancreatitis varies in its severity from mild
      inflammatory process within pancreatic tissue to severe necrotic pancreatitis
      with involvement of regional tissues and remote organs leading to the multi organ
      dysfunction syndrome. Acute pancreatitis results in hypermetabolic, highly
      catabolic state and negative nitrogen balance, the degree of which is directly
      related to the severity of the disease and high mortality (up to 40%). The aim of
      nutritional support is to establish positive nitrogen balance without stimulating
      pancreatic secretion ofproteolytic enzymes and auto-digestion. Traditionally,
      fasting ("putting the pancreas at rest") with or without total parenteral
      nutrition was considered as standard of care. Current knowledge regarding the
      importance of integrity of intestinal mucosal barrier suggests that early enteral
      feeding should be implemented. Despite several randomised controlled trials
      comparing total parenteral with enteral nutrition, some guidelines and
      recommendations, there are still unsolved questions regarding the type and amount
      of fluids and calories that should be provided as well the use of the immune
      enhancing diets.

PMID- 23120842
TI  - [Pancreatitis in cardiac patients].

PMID- 23120843
TI  - [Acute childhood pancreatitis caused by valproate].
AB  - Signs of pancreatitis in children are simmilar to those in adults: disturbed
      general condition, abdominal pain, vomitting, elevated amylase level. Mainstays
      in intensive therapy and indications for surgical interventions are also sim
      milar. Contrary to adults, in childhood pancreatitis adverse effects of various
      drugs are common causes. Natrium valproate, antiepileptic drug in use for many
      years, can rarely induce pancreatitis. We report of such case in a girl treated
      with valproate for Rett's syndrome. Abdominal ultrasound can be unspecific in
      acute pancreatitis. If clinical signs and amylases elevated in a child on
      valproate therapy do not suffice, abdominal computer tomography should be done to
      confirm the grounded suspicion.

PMID- 23120844
TI  - [Intra-abdominal hypertension and abdominal compartment in severe acute
      pancreatitis].

PMID- 23120845
TI  - [CT diagnosis and the Balthazar Index of severity in acute pancreatitis].

PMID- 23120846
TI  - [Treatment of acute pancreatitis].
AB  - BACKGROUND: Acute pancreatitis is an autodigestive disease in which the
      pancreatic tissue is damaged by the digestive enzimes produces by the acinar
      cells and is associated with severe upper abdominal pain. The severity of acute
      pancreatitis ranges from edema to necrosis of the gland. The edematous form of
      the disease occurs in about 80-85% of patients and is self-limited, with recovery
      in few days. In the 15-20% of patients with the most severe form of pancreatitis,
      hospitalization is prolonged and commonly associated with infection and other
      complications including multiple organ failure. The main causes of acute
      pancreatitis in adults are gallstones, other gallbladder (biliary) diseases and
      alcohol abuse. Treatment of acute pancreatitis-depends on the severity oft he
      condition. Generaly, the patients need, hospitalisation with administration of
      intravenous fluid to help restore blood volume, pain control, supplemental oxygen
      as required and correction of electrolite and metabolic abnormalities. Antibiotic
      prophylaxis has not been shown as an effective preventive treatment. Early
      enteral feeding is based on a high level of evidence, resulting in a reduction of
      local and sistemic infection. Begin oral feeding once abdominal pain has resolved
      and the patients regains appetite. The diet should be low in fat and protein.
      Patients suffering from infected necrosis causing clinical sepsis, pancreatic
      abscess or surgical acute abdomen are candidates for early intervention.
      CONCLUSION: During recent years the management of acute pancreatitis has changed.
      This has been due particulary in response to the general availability of computed
      tomography, improved intensive care facilities, knowledge about the central role
      of pancreatic infection and refinements in surgical and other interventional
      techniques.

PMID- 23120847
TI  - [Biochemical markers in assessment of severity and prognosis of acute
      pancreatitis].
AB  - The authors reveal and discuss the role of novel biochemical parameters in early
      diagnosis of acute pancreatitis and assessment of the severity of the disease.
      These biochemical parameters, beside routinely used amilase and lipase, might
      enable us to early identify those patients who are at risk of developing severe
      form of pancreatitis or complications. These parameters include trypsinogen
      activation peptide (TAP), C-reactive protein (CRP, tripsinogen-2, procalcitonin,
      phospholipase-A2 (PLA2), carboxypeptidase activation peptide (CAPAP) and
      interleukin-6 and 8 (IL-6, IL-8). Although these markers are still not
      incorporated in routine clinical practice, IL-6, IL-10, procalcitonin and
      trypsinogen activation peptide seem to have a good chance to be used as a new
      biochemical markers in assessment of severity and prognosis of acute
      pancreatitis.

PMID- 23120848
TI  - [Analgesia in pancreatitis].

PMID- 23120849
TI  - [ERCP and acute pancreatitis].

PMID- 23120850
TI  - [Antibiotics for pancreatitis--still controversial?].
AB  - Summary. Infection frequently complicates the course of severe acute pancreatitis
      and might manifest as infected pancreatic necrosis, pancreatic abscess or an
      infected peripancreatic fluid collection. Pancreatic necrosis occurs in roughly
      21% of all cases of pancreatitis. In patients with necrosis involving more than
      one-half of the pancreas, the incidence of subsequent infection is as high as 40%
      70%. More than 50% of these infection yield a polymicrobial isolate with
      predominance of enteric bacteria but recently, the microbiologic pattern has
      shifted toward more resistant gram-negative bacilli, gram-positive cocci and
      yeast, a reflection of exposure to broad-spectrum antimicrobial agents. Given the
      morbidity associated with infection, many commentators have advocated
      prophylactic antimicrobial therapy in patients with necrosis to the point that
      this measure has been incorporated into routine practice. However, there is
      controversy over the risks and potential benefit. Currently, advise against the
      routine use of prophylactic systemic antibiotics and antifungals (side-effect
      selection of resistant microbes and fungi). However, there may be some patients
      who benefit from prophylaxis, and additional studies and investigations are
      ongoing. Antibiotics should not be given early in the disease course because most
      symptoms are due to the inflammatory response, not an infectious etiology.
      Antibiotics are indicated when CT scans indicate a pancreatic phlegmon,
      empirically in the case of severe pancreatitis associated with septic shock, or
      with documented fine - needle aspiration biopsy identification of bacteria. Under
      those circumstances, antibiotic coverage is warranted to prevent systemic gram
      negative sepsis. Infected pancreatic necrosis should be treated with carbapenems
      because they can effectively penetrate pancreatic tissue. Other conditions, such
      as biliary pancreatitis associated with cholangitis, mandate antibiotic coverage.

PMID- 23120851
TI  - [Microbiologic problems in acute necrotizing pancreatitis with emphasis on fungal
      infections].

PMID- 23120852
TI  - [Rare complications of Salmonella enteritidis infection].
AB  - We report 64-year old patient who was admitted in ICU with left side ileofemoral
      thrombosis and splenic abscess during Salmonella enteritidis infection.

PMID- 23120853
TI  - [Evaluation of severity of acute pancreatitis using prognostic indicators and the
      Atlanta Classification].

PMID- 23120854
TI  - [Pancreatitis--indications for surgical treatment].

PMID- 23120855
TI  - [The role of minimal invasive surgery in the treatment of acute pancreatitis].

PMID- 23120856
TI  - [Splanchnic flow in acute pancreatitis].

PMID- 23120857
TI  - [Hyperlipidemic pancreatitis].

PMID- 23120858
TI  - [Reorganization of the emergency medical service].

PMID- 23120859
TI  - [Croatian Institute of Emergency Medicine].

PMID- 23120860
TI  - [Advancement of emergency medical care--organization of emergency hospital
      admission].

PMID- 23120861
TI  - [Telemedicine in the reorganization of emergency medical service].

PMID- 23120862
TI  - [Specialties in emergency medicine].

PMID- 23120863
TI  - Emergency medicine in Slovenia--emergency center, prehospital emergency medicine
      and academic emergency medicine.
AB  - Public health service is organized in such a manner so as to ensure all the
      inhabitants of the Republic of Slovenia the emergency medical assistance
      available at all times, including emergency transport and provision of emergency
      medicinal products as soon as possible and as close to the date of their
      manufacture as possible and during transport. Emergency medical assistance means
      the implementation of necessary measures by doctors and their teams with persons
      whose life is imminently threatened due to illness or injury and persons,
      respectively, who could be affected by such a risk in a short period of time
      according to the symptoms. Emergency calls are received and processed by the
      emergency medical assistance service which forms an integral part of the public
      health service network. Emergency patients with life-threatening trauma or
      disease are treated by prehospital emergency physicians at the scene and during
      transport. Emergency patients are guaranteed to be reached by an appropriate
      emergency vehicle and a respective crew within 10 minutes in 80% of the responses
      and within 15 minutes in 95% of cases. In Slovenia was established 30 years ago
      the so-called Franco-German system, with a highly developed pre-hospital
      emergency physician service and interdisciplinary hospital-based emergency
      medicine on different departments (trauma center, department for internal
      intensiv medicine, department of ananstesiology, department for neurology and
      pediatrics department (1). This gap is now closing fast because of the rapid
      advancement of hospital-based emergency medicine in Slovenia. In-hospital
      emergency medicine has been reorganized in many hospitals during the last few
      years. Economic and quality arguments have initiated the development of
      departments for emergency medicine in Slovenia. In the future, this will lead to
      new qualification criteria for physicians working in these departments. Four
      specific recommendations for development and organizations emergency medicine are
      required: the recognition as a specialty, the specialist training programme, the
      professional organization of emergency physicians and the presence of academic
      emergency centres (2). Slovenia is one of the 11 European countries who recognize
      hospital-based emergency medicine as a specialty (3, 4). This is 5-year specialty
      training (based on European curriculum) and the curriculum follows a symptom
      oriented approach to emergency medicine, and includes a skilled description of
      the key competencies of the future trained emergency physicians (4). Slovenia has
      very well organised prehospital on-physician based emergency service and new
      qualification criteria for those physicians in emergency departments, therefore,
      need to be developed with primary education trainers for emergency medicine. In
      the model of integration of prehospital and hospital emergency medicine in
      academic emergency centers, emergency physicians work equal in ED and in the
      field on the method of rotation without changes of actual prehospital on
      physicians based EMS.The integrative model have one in-door for emergency
      patients, mobility ofprehospital emergency physicians, a nurse-driven triage
      system and support of primary care physicians as gatekeepers.

PMID- 23120864
TI  - [Treatment of patients with acute asthma exacerbation].
AB  - Asthma is a chronic inflammatory disease of the airways. The global prevalence of
      asthma ranges from 1% to 18% of the population, so it remains a common problem
      with enormous medical and economic impacts. In majority of patients, asthma can
      be well controlled with simple regimens of inhaled anti-inflammatory and
      bronchodilating medications. However, some patients tend to suffer from poorly
      controlled disease in terms of chronic symptoms with episodic severe
      exacerbations. Major factors that may be related to the emergency department
      visits and hospitalisation include prior severe attacks, nonadherence to
      therapeutic regimens, inadequate use of inhaled corticosteroids, poor self
      management skills, frequent use of inhaled short-acting beta-agonists, cigarette
      smoking, poor socioeconomic status and age over 40 years. Severe exacerbations of
      asthma are life-threatening medical emergencies and require careful brief
      assesment, treatment according to current GINA (Global Initiative for Asthma)
      guidelines with periodic reassesment of patient's response to therapy usually in
      an emergency department.

PMID- 23120866
TI  - [Pneumonia: a diverse and severe disease].

PMID- 23120865
TI  - [Care of patients with exacerbation of chronic obstructive lung disease].
AB  - Exacerbations of chronic obstructive pulmonary disease are a common cause of
      hospital admission. They have a profound effect on the quality of life, disease
      progression and healthcare costs. The central event is amplified inflammation
      with many biomarkers who are not in clinical use. Severe dyspnea and large volume
      of purulent sputum are typical clinical presentation of exacerbation due to viral
      or bacterial infections. Bronchodilators and corticosteroids are the mainstay of
      pharmacologic therapy of exacerbation, antibiotics are useful in the presence of
      purulent sputum and other signs of respiratory infection. Acute respiratory
      failure in patients with exacerbation of COPD demand controlled oxygen therapy
      and noninvasive ventilation or conventional mechanical ventilation. Important
      advances have been made in understanding etiology and pathogenesis of
      inflammation in exacerbation of COPD. There is a proposal for approach to such
      patients in emergency departement and a guidelines for pharmacologic therapy and
      oxygen therapy.

PMID- 23120867
TI  - [Rational therapy in emergency states in pulmonology].

PMID- 23120868
TI  - [Mountain rescue medical education in Croatia].

PMID- 23120869
TI  - [Poisonous snake bites].

PMID- 23120870
TI  - Helicopter emergency medical service in mountainous areas.
AB  - The outcome of patient care can be dramatically improved by bringing rapid rescue
      medical treatment to the scene and by rapid transport to a medical facility. In
      mountainous areas this is usually possible only with the use of helicopters. ICAR
      MEDCOM suggests international standards for competent and safe response to
      medical problems in mountainous and wilderness areas. Rescue helicopters should
      work within the existing emergency medical system with appropriate mountain
      rescue and medically-trained personnel and with medical and rescue equipment on
      board. Safety is most important issue in mountain rescue. Activation and approach
      time should be as short as possible. All persons responsible for activation and
      realization of a helicopter rescue operation should be aware of all specific
      problems in the mountains and wilderness.

PMID- 23120871
TI  - [Expedition medicine].
AB  - Expedition and wildeness medicine is a term that combines rescue medicine, sport
      medicine as well as more specific branches as polar or high altitude medicine. It
      is being intensively studied both at the reaserch institutes and on expeditions.
      Ophtalmologists are concentrated on the reaserch of HARH (High Altitude Retinal
      Hemorrhage), neurologists on HACE reaserch (High Altitude Cerebral Edema),
      psychologists are developing tests to decsribe cognitive functions and many
      physicians are being trained to work in extreme enviroment. The result of all
      this effort are numerous new findings in pathophysiology and therapy of altitude
      illness, increased security on expedition and further development of
      expeditionism.

PMID- 23120872
TI  - [Emergency therapeutic interventions in acute allergic conditions].

PMID- 23120873
TI  - Ultrasound, new strategy, new pharmacological approach and clinical research
      priorities for cardiopulmonary resuscitation.
AB  - The group of experts appointed to review specific resuscitation topics and
      identify knowledge gaps. The experts compiled and organized these knowledge gaps
      and, through a process of consultation and consensus, identified areas of
      priority for clinical research. The process included evidence evaluation, review
      of the literature, and focused analysis. The results, recommendations and
      guidelines were published 2007 in basic journals for CPR (Circulation and
      Resuscitation). We compared some of them with the clinical trials in
      cardiopulmonary resuscitation in Center for Emergency Medicine Maribor.

PMID- 23120874
TI  - [Acute coronary syndrome at the Institute of Emergency Medicine in Sarajevo].
AB  - The coronary illness is the first cause of death and falling ill in the world. It
      is considered that, in more than 50% of cases, it is about the illnesses of heart
      and blood vessels as the cause of death. These results indicate the necessity to
      prevent and to treat correctly the persons suffering from cardivascular
      illnesses. The coronary illness represents the ischaemia myocardium as the
      consequence of reduced blood flow through the coronary arteries (one or more
      branches). There are more and more young persons suffering from this illness. In
      the Emergency Medical Institute Sarajevo, a retrospective-prospective analysis of
      patients with working diagnosis of ACS was carried out for the period of one year
      (01.01-31.12. 2008). The patients (279) were analyzed by gender, years of age,
      months (*when ACS occurred), seasons of year and hours of occurrence of ACS,
      therapy by applying low-molecular heparin and prospectively by symptoms, as well
      as usual risk factors.

PMID- 23120875
TI  - The outcome of cardiac arrest the years before and after introduction of Lucas in
      the ambulances.

PMID- 23120876
TI  - [Traffic accidents as a reason for team intervention at the UHMP in Zagreb during
      2008]].

PMID- 23120877
TI  - Road accidents in Prishtina in the period 2005-2008.
AB  - The results of the research conducted in the Emergency Center during the period
      2005 - 2008 are showing an enormous increase in the number of road traffic
      accidents. In this increase, except reasons mentioned above and among others, the
      following factors have contributed: enormous increase of number of persons
      equipped with driving license (5,6), driving speeds above permitted norms are
      considered a primary cause of road traffic accidents. An important factor that
      has influenced the cause of accidents was the consumption of alcohol before or
      during driving the vehicle, non-wearing of seat belts and protective helmets. The
      worldwide data show that the role of the safety belts enables a reduction of
      health consequences (1-3). We don't have any precise data from the Kosovo police
      service in regard to the existing correlation between wearing the safety belt and
      the degree of damage to the injured, as these data are not taken by the traffic
      police when an accident happens. The negligence of pedestrians continues to
      remain a matter of concern and the pedestrians are considered as a vulnerable
      group (7.8).

PMID- 23120878
TI  - [Exposure of emergency medical personnel to infective disease agents].

PMID- 23120879
TI  - [The place, role and importance of emergency medical care in the Serbian health
      care system].
AB  - Emergency medical assistance is immediate, the current medical support that is
      provided hurted person to avoid any possible harmful consequences for his life
      and health. Emergency medical aid is part of the health care system that is
      rarely thought, but is still expected to be available always and continuously in
      case of need. Emergency medical assistance should always be available throughout
      the territory where people live, because there is no adequate replacement.
      Emergency Medical Services and emergency medical transportation services are
      health care that is provided in terms of all persons in the state of medical
      urgency. In urgent or emergency conditions, health care can be provided on the
      site of injuries and disease or health institution. Cases of medical urgency are
      ranked by degrees. The first and most difficult level of medical urgency indicate
      all urgent pathological conditions, diseases, injuries and poisoning, which occur
      in the workplace and public places. To expect medical team of emergency medical
      assistance at the scene intervened medical urgency, it is necessary to make call
      it. Call the phone number refers to the 94. Call sent to this number to receive
      orderly dispatcher. Dispatchers are employees who perform their work in the
      dispatching center. They appear in the phone number 94, made the assessment and
      screening calls, worry about the degree of urgency, and the absorption team,
      which team is the nearest place of the event. After received calls they send
      expert medical teams to the place of accident. In the dispatching center work
      always doctor and medical technician. Emergency medical care cases is a great
      professional and educational challenge and imposes a constant need in education
      of doctors and the whole emergency medical teams. Education of all employees in
      the state of emergency care is required continualy and for students too to
      receive new knowledge in the field of medical urgency by various professional
      purposes.

PMID- 23120881
TI  - Future jobs depend on a science-based economy.

PMID- 23120880
TI  - [The Croatian Society of Dragon Brothers established October 10 1909 now tha
      Zagreb Rescue Society].

PMID- 23120882
TI  - The voting gene.

PMID- 23120884
TI  - You are here.

PMID- 23120883
TI  - The autism pill.

PMID- 23120885
TI  - A shot in the arm.

PMID- 23120886
TI  - Some don't like it hot.

PMID- 23120887
TI  - From tail chasing to hand washing.

PMID- 23120888
TI  - Break more to break less.

PMID- 23120889
TI  - Helpless by design?

PMID- 23120890
TI  - The last frontier.

PMID- 23120891
TI  - Virtues of the virtual autopsy: medical imaging offers new ways to examine the
      deceased.

PMID- 23120892
TI  - To track my thief.

PMID- 23120893
TI  - The inner life of quarks: what if the smallest bits of matter actually harbor an
      undiscovered world of particles?

PMID- 23120894
TI  - Grow your own eye: biologists have coaxed cells to form a retina, a step toward
      growing replacement organs outside the body.

PMID- 23120895
TI  - Global warming: faster than expected? Loss of ice, melting of permafrost and
      other climate effects are occrring at an alarming pace.

PMID- 23120896
TI  - The strangest bird: recent fossil discoveries reveal the surprising evolutionary
      history of penguins.

PMID- 23120897
TI  - America's science problem.

PMID- 23120899
TI  - A new enlightenment: quantum theory once seemed like the last nail in the coffin
      of pure reason. Now it's looking like its savior.

PMID- 23120898
TI  - Autism and the technical mind: children of scientists and engineers may inherit
      genes that not only confer intellectual talents but also predispose them to
      autism.

PMID- 23120900
TI  - Shock and awe.

PMID- 23120901
TI  - Tag--you're sick: patterns of personal contact in a hospital reveal true pathways
      of transmission.

PMID- 23120902
TI  - [Scientific and methodologic approaches to evaluating medical management for
      workers of Kazakhstan].
AB  - The article covers topical problems of workers' health preservation. Complex
      research results enabled to evaluate and analyze occupational risks in leading
      industries of Kazakhstan, for improving scientific and methodologic approaches to
      medical management for workers subjected to hazardous conditions.

PMID- 23120903
TI  - [Topical problems and measures to protect ambient air in major industrial
      regions].
AB  - The authors discuss main causes of ambient air pollution in urban regions, with
      evaluation of various types of ambient pollutants. The article covers main ways
      to prevent pollution influences on population.

PMID- 23120904
TI  - [Natural climatic charcteristics of Temirtau city].
AB  - Studies of meteorologic parameters in Temirtau city enabled to define comfort
      residence zones in accordance with natural climatic characteristics of the area.
      Findings are that Temirtau city territory includes districts of comfort (central
      part of the city), subcomfort (water basin district), discomfort

PMID- 23120905
TI  - [Neurologic and neuro-psychologic changes in residents of Taraz town].
AB  - The study covered occurrence of clinical and psychologic disorders in
      cerebrovascular diseases. Examination involved 840 individuals aged 20 to 59
      years. The examinees demonstrated early clinical manifestations of
      cerebrovascular diseases with vegetative dysfunction as asthenic and
      hypochondriacal syndromes. The encephalopathy course was characterized by
      prevailing asthenic and neurotic syndrome, with cognitive disorders and emotional
      depletion.

PMID- 23120906
TI  - [Causes of increased noise levels in Kazakhstan cities].
AB  - The article deals with data on causes of high noise levels in Kazakhstan cities
      and on role of transport noise in urban environment. Development of all kinds of
      transport, traffic routes caused humans exposure to intense noise levels. Traffic
      contents and intensity appeared to be major factors changing noise mode of city
      transport traffic.

PMID- 23120907
TI  - [Graphic approach to evaluating environmental state of industrial cities for
      specification of public hygienic safety].
AB  - The article presents graphic data of ecologic research determining factors of
      various origins. New software designed helps to define zones heterogenous in
      human health risks within residential areas of industrial cities.

PMID- 23120908
TI  - [Evaluating morbidity in Taraz town according to medical and biologic studies].
AB  - The article presents evaluation of morbidity in Taraz town according to medical
      and biologic research. Findings are possibly increased morbidity in following
      diseases groups: gastro-intestinal tract, endocrine, hemopoietic and urinary
      systems in dwellers of Taraz town, if compared to the reference group--dwellers
      of Shouchinsk town.

PMID- 23120909
TI  - [Results of cardiovascular funtional state evaluation in female residents of
      technogenically charged regions of Kazakhstan Republic].
AB  - Prenosologic research in female dwellers of various regions with technogenical
      load revealed unfavorable changes in their health state. The examinees' state
      appeared to be characterized by increased deficit of functional resources.

PMID- 23120910
TI  - [Evaluating morbidity of population in Ekibastouz and Shouchinsk cities].
AB  - The authors presented comparative analysis of diseases incidence among Ekibastouz
      city population. In the incidence structure in Ekibastouz, the leading place was
      occupied by respiratory diseases, digestive system diseases, eye disorders,
      locomotory problems, traumatism and poisonings.

PMID- 23120911
TI  - [Prenosologic diagnosis of ecologically dependent disorders in females of urban
      area].
AB  - The data obtained on health state of females varying in age and residing in
      ecologically unfavorable area demonstrate changes in barrier, hormonal and
      microelemental status - that necessitate defining risk groups for ecologically
      dependent diseases formation.

PMID- 23120912
TI  - [Psychophysiologic criteria determining perfomance in shift team workers].
AB  - Individual strategies of adaptation to work process appeared to manifest in
      changed functioning of central nervous system, mental performance and to be
      associated with typologic features of operators. The authors revealed
      psychophysiologic criteria that enable operators to succeed in work operations
      during 12-hour working shift over 14 days of duty.

PMID- 23120913
TI  - [Assessment of the incidence of miners vakhtova of the work organization].
AB  - Analysis of the incidence of HLA miners working open coal mining showed that the
      impact of unfavorable factors ecological industrial environment in different
      seasons of the year, related to the rotational mode of labor organization,
      modifies biological rhythms in life processes and contributes to violations of
      the state of health.

PMID- 23120914
TI  - [Regulation and control of hexane level in air of workplace].
AB  - The article covers discussion on necessity of changing MAC for hexane in air of
      workplace. That is justified by health disorders in the workers, supported by the
      authors' experimental studies. The authors analyzed methods to control hexane
      levels in air of workplace, suggested specific standardized method assessing
      hexane in air of workplace and in ambient air.

PMID- 23120915
TI  - [Lacrimal drainage system examination using functional multidetector computed
      tomography].
AB  - Computed tomography images are analyzed in patients with and without lacrimal
      drainage system abnormalities. Potential of functional multidetector computed
      tomography in dacryostenosis is showed.

PMID- 23120916
TI  - [Optic neuritis and optic ischemic neuropathy: the problem of differential
      diagnosis].
AB  - Based on a numerous data (220 patients, 285 eyes) clinical criteria of
      differential diagnosis of optic neuritis and nonarteritic ischemic optic
      neuropathy are studied. Neuronal network method was used for multivariate
      analysis of studied parameters, that allowed to estimate linear and nonlinear
      correlations of different factors, significance of every diagnostic criteria for
      the identification of etiology of optic neuropathies.

PMID- 23120917
TI  - [Comparative study of central and peripapillary retina in primary open-angle
      glaucoma using spectral-domain optical coherence tomography].
AB  - The aim of the study was to compare outer retinal layers in primary open-angle
      glaucoma (POAG) using spectral-domain optical coherence tomography (OCT). 15
      patients (27 eyes) and 16 normal subjects (32 eyes) were examined. Patients were
      examined using OCT Spectralis ("Heidelberg Engineering", Germany) in order to
      analyze outer retinal layers and evaluate beta-zone extent. Significant
      difference such as thining of retinal pigment epithelium/Bruch's membrane (RPE/
      BrM) complex was found in OCT images of outer retinal layers. Negative
      correlation of RPE/BrM complex thickness and peripapillary beta-zone extent was
      found. Changes of central and peripapillary retina detected using spectral-domain
      OCT may be considered for diagnosis and monitoring of POAG.

PMID- 23120918
TI  - [Production of timolol containing calcium-phosphate nanoparticles and evaluation
      of their effect on intraocular pressure in experiment].
AB  - Methodology for production of calcium-phosphate nanoparticles is developed and
      its efficacy as a drug carrier system is estimated by example of timolol.
      Conditions for production of particles with optimal size and resistance are
      determined, methodology of loading of particles with timolol is developed.
      Physical parameters of particles (form, size, relief), kinetics of saturation
      with drug and its release are studied. Packaging of timolol into calcium
      phosphate nanoparticles was showed to enhance and prolong its hypotensive effect
      in experiment on healthy rabbits.

PMID- 23120919
TI  - [Retrospective analysis of causes of enucleations after anti-glaucomatous
      surgery].
AB  - Proximate causes of intraocular pressure (IOP) decompensation accompanied with
      persistent pain syndrome were determined based on results of morphological
      examination of 59 eyes enucleated due to terminal previously operated glaucoma
      and medical history analysis. Excessive scarring, formation of solid hyalinized
      membrane in the site of filter pad, closure of anterior chamber angle with
      synechia as an outcome of chronic iridocyclitis and inappropriate surgical
      approach lead to increase in the resistance of the aqueous humor outflow and
      result in glaucoma decompensation causing complications that necessitate
      enucleation. The most common complications are the following: bacterial corneal
      ulcer with potential perforation and endophthalmitis, hemorrhagic choroidal
      detachment, vitreous hemorrhage, persistent pain syndrome and phthisis bulbi.

PMID- 23120920
TI  - [Recovery of visual functions after multifocal intraocular lens implantation].
AB  - In order to study the features of visual system (VS) recovery after multifocal
      correction we examined in dynamics visual functions and subjective satisfaction
      with sight quality in 64 patients (mean age 52 +/- 2.5 years) at different time
      after binocular implantation of apodized refractive-diffractive intraocular lens
      (IOL) Acrysof Restor. These patients before surgery and 30 healthy subjects (60
      eyes, mean age 48 +/- 4.5 years) served as controls. Over 6 months after surgery
      progressive improvement of mean visual acuity in the main distances (40, 70-80 cm
      and 5 m), contrast sensitivity and subjective satisfaction were observed. Gradual
      increasing of VS resolution suggests the need of search of postoperative
      rehabilitation methods that would provide faster adaptation to new optical
      conditions.

PMID- 23120921
TI  - [Static correction of lagophthalmos in chronic facial palsy].
AB  - Choice of surgical option for lagophthalmos correction (use of encircling
      allotendinous string or fixation of medial aspect of the lower tarsal plate) in
      patients with chronic facial palsy is proved. This technique was reinforced with
      dissection of the tendon or superior tarsal muscle resection and lateral
      canthopexy. The advantages of surgical methods considering clinical aspects (in
      particular the degree of medial canthal tendon laxity) are shown.

PMID- 23120922
TI  - [Optimization of complex treatment in ocular toxoplasmosis and concurrent
      infections].
AB  - 137 patients (177 eyes) with verified toxoplasmic uveitis, retinitis,
      chorioretenitis were observed. Among them 65 patients had concurrent infections:
      tuberculosis, herpes simplex and chlamydia. Routine ophthalmologic, clinical and
      laboratory examination was performed. The results of intensive treatment in acute
      and chronic phases are presented, the staged drug pathogenic treatment including
      methods of specific therapy, based on differential approach to anti-inflammatory
      agents use, was provided. Early diagnosis and appropriate management including
      combined treatment of concurrent infections improves treatment efficacy and
      allows to achieve excellent results.

PMID- 23120923
TI  - [Clinical classification of incomitant strabismus].
AB  - Based on study of etiology, pathogenesis, clinical course, results of treatment
      of 489 patients aged from 1 till 73 years old with incomitant strabismus and
      integration of literature data clinical classification of incomitant strabismus
      was developed. Classification considers type and degree of extraocular muscle
      impairment (paralysis, palsy, pseudoparalysis, atypical forms), localization of
      damage (III, IV, VI cranial nerves, concurrent nerve damage), level of damage
      (cranial, orbital, combined), etiology and pathogenesis (local or systemic
      disease), age of manifestation (congenital, early and lately acquired), clinical
      manifestations (direction of globe deviation, forced head position, amblyopia,
      orbital fractures and soft tissue entrapment), presence of binocular diplopia (in
      primary or all gaze directions, in secondary gaze directions, without diplopia).

PMID- 23120924
TI  - [Maturation and plasticity of visual system: neurogenesis, synaptogenesis, and
      myelogenesis. Report I. Retina and retinogeniculate projections].
AB  - In this review up-to-date conception of retinal neurogenesis and synaptogenesis
      is presented, specific stages information of cellular and synaptic structure of
      retinal synaptic pathways and their propable mechanisms are briefly discussed.
      Neurogenesis is largely determined geneticaly, and molecular cues are assumed to
      play a crucial role in retinal synaptogenesis. The initially established retinal
      synaptic circuitry is profoundly refined during postnatal development to form
      specific synaptic pathways. In early developing retina, retinal ganglion cells
      fire periodic bursts of action potentials that are highly correlated and
      propagate across the retina in a wave-like fashion. The model of retinal-wave
      dependent synaptic plasticity seems to be suited for the Hebbian learning rule.

PMID- 23120925
TI  - [Sarcoidosis: etiology, pathogenesis, epidemiology, risk factors, clinical
      presentation].
AB  - Sarcoidosis is a chronic idiopathic multisystem granulomatous inflammatory
      disease of unknown etiology. Prevalence of this condition is approximately 3-5:
      100 000 with the highest incidence at the age of 25-40 years old and no gender
      predomination. Early morbidity, disability and severe prognosis worsen patient's
      condition and make them socially limited. In some cases ocular involvement and
      vision loss aggravate general condition of the patients. Ocular involvement in
      sarcoidosis occurs in 10-75% patients. At the same time some data confirm the
      fact that in 7% of patients ocular damage is the presenting sign making them come
      to an ophthalmologist whereas orbital involvement may present in systemic disease
      only. Unclear etiology and clinical similarity with other conditions cause
      difficulties in early diagnosis and monitoring of patients with sarcoidosis.

PMID- 23120926
TI  - [Morphological and functional features of vitreous].
AB  - The structure of vitreous is discussed in the article. Its morphologic
      characteristics are described with consideration of topography and structural
      features. General vitreous anatomy and its distinct compartments are highlighted.
      Native and foreign literature concerning biological, biochemical and biophysical
      properties is analyzed. The value of vitreous developmental and structural
      features in pathogenesis of some pathologic conditions is estimated The
      parameters of distinct analyzed characteristics essential to form spatial
      sonographic image are shown.

PMID- 23120927
TI  - [Laser cyclodestructive procedures in glaucoma treatment].
AB  - The history of development of cyclodestructive procedures is given, their
      advantages and disadvantages are discussed. Different techniques of laser use,
      relative and absolute contraindications to various laser cyclophotodestructive
      procedures are considered. Their potential complications and effecting mechanisms
      are discussed.

PMID- 23120928
TI  - [Up-to-date opportunities of IOL fixation in deficiency of lens capsule support].
AB  - Native and foreign literature concerning up-to-date techniques of surgical
      treatment of aphakia in deficiency of lens capsule support is reviewed Their main
      advantages and disadvantages are discussed.

PMID- 23120929
TI  - [Treatment of retinal detachment in optic nerve pit].
AB  - Clinical presentation, pathogenesis and treatment of optic nerve pit are
      reviewed. Treatment options of central retinal detachment in optic nerve pit
      known since 1882 and still used are discussed.

PMID- 23120930
TI  - Some factors associated with non-adherence to antiretroviral therapy (ART) in
      people living with HIV/AIDS (PLHA) in Tanzania: a case study of Dar es Salaam
      region.
AB  - OBJECTIVES: Tanzania is one of the nations that are highly affected by HIV/AIDS
      epidemic. Invention of ARVs (Anti -Retroviral) brought hope of extended life to
      people living with HIV/AIDS (PLHA). Though ARV's are administered in several
      clinics particularly in Dar es Salaam, there is a problem to adherence. Some
      factors associated with non-adherence are investigated and ways to optimize
      adherence are suggested. METHODS: This study was undertaken at three treatment
      and care clinics in Dar es Salaam. A sample of 197 individuals on ARV and 30
      health care providers were interviewed. The sample comprised of 76 % females and
      24% males, with mean age 34. About 74% of individuals on ARV were aged between 25
      - 45 years. Logistic Regression and survival analysis models were used in the
      analysis. RESULTS: Individuals on ARV recommended factors responsible for non
      adherence as lack of awareness 63.5%, stigma 56%, side effects 53.3%, and costs
      28%. Other factors were being busy 25.4%, away from home 21.3%, forgetting 12.2%
      and ARVs out of stock 10.2%. Proportion of PLHA lost to follow up was 26%.
      Awareness and side effects were found to be statistically significant, with p
      values of 0.042 and 0.068 respectively (alpha = 0.1). The median survival time
      for individuals on ARV was 42 months (95% CI: 41-44) with survival rate of above
      0.7. Log-rank test showed significant differences between the male and female on
      having a shorter time to death. Females seemed to survive longer than males
      suggesting that females adhere more to ART than males. CONCLUSION: This calls for
      emphasis on HIV/AIDS education to the society especially to sensitize men.
      Another suggestion is that when a woman gets pregnant, both the expectant mother
      and father should attend maternal clinic so that they both take HIV test so as to
      increase man's participation.

PMID- 23120931
TI  - Cervical cancer: a missed health priority in Tanzania.
AB  - Cervical cancer is a malignant neoplasm of the cervix uteri. It is the second
      commonest cancer in women worldwide and is among the largest causes of global
      cancer mortality. Human papilloma virus (HPV) which is transmitted sexually,
      particularly subtypes 16 and 18 are responsible for causing majority of cervical
      cancer cases worldwide. The disease is one of the most preventable and curable
      carcinomas if detected and treated at an early enough stage. The effective
      prevention and control of the disease depends on, among others, the effective
      screening program coupled with knowledge and awareness of women population on the
      disease's risk factors and available screening services. Pap-test screening that
      is widely used in Western countries and proved to be effective in reducing the
      incidence of cervical cancer is not so popular in Tanzania, and so is HPV
      vaccine. This review examines the literatures on cervical cancer situation and
      explores various evidence-based cost-effective strategies and approaches that
      could be employed to confront the rising cervical cancer burden in the country.

PMID- 23120932
TI  - Parasitic infection of the digestive tract in children in a regional hospital
      center in Gharb (Kenitra, Morroco): some epidemiological features.
AB  - Intestinal parasites are very common in children. We propose to study the
      prevalence and Epidemiological profile of the port of intestinal parasites in 300
      children hospitalized in the Regional Hospital of Gharb area (Kenitra, Morocco)
      from June to December 2007. This study Identified 11 intestinal parasites. Of the
      300 children, 157 at least one intestinal have Parasitism was 52.3% with 91 boxes
      of poly-Parasitism. Among the intestinal protozoan Identified, Is The first
      Amebiasis intestinal parasites. The rate of infestation of Amoebiasis IS 46.5%,
      Followed by Blastocystis hominis (28.7%) of giardiasis (14%). That shows 128
      children in the study population IS a carrier of Various species of helminths,
      the main ones: Enterobius vermicularis (35%), Ascaris lumbricoides (29.9%),
      Trichuris trichiura (10.2%), Hymenolepis nana (3.8%) and Taenia saginata (2.5%).
      The survey shows the age group most That exposed to intestinal parasites IS
      Between 1 and 4 years and sex does not appear to significantly interferes in the
      distribution of different parasite species. The results show the necessity of
      improvement of the sanitation of the environment and the health education of the
      population. Then will Come the deworming campaign of which will be therefor
      effective.

PMID- 23120933
TI  - Determinants of HIV-VCT utilization among secondary schools teachers in Thika
      district, Kenya.
AB  - BACKGROUND: HIV/AIDS is a global health problem whose emergence has introduced
      new dimensions to health care delivery worldwide including Voluntary Counselling
      and Testing (VCT). Despite its proven benefits, high knowledge of VCT and its
      availability, its uptake is varied and often poor. It is commonly argued that
      teachers in Sub-Saharan African (SSA) countries have relatively high HIV
      prevalence rates than the general population. AIDS is claiming teachers more
      quickly than they can be trained in many countries and is the leading cause of
      death among teachers in the SSA countries. OBJECTIVE: To identify determinants of
      HIV-VCT uptake amongst secondary schools teachers. METHOD: A cross-sectional
      survey involving 246 secondary school teachers randomly selected in Thika
      district, central Kenya. RESULTS: HIV-VCT utilization among secondary school
      teachers was 30.5%. The younger and less experienced teachers were more likely to
      utilize HIV-VCT services than the older and more experienced ones (Likelihood
      ratio, P = 0.004). Private school teachers were more likely to utilize HIV-VCT
      services than those of the public schools (OR = 2.356, 95% CI limit, 1.082
      5.128). Teachers who were scared by the HIV prevalence in their area were three
      times less likely to utilize HIV-VCT services (OR = 0.312, 95% CI, 0.104-0.936).
      The teachers who had not sought HIV-VCT service were less likely to perceive HIV
      VCT services as beneficial (Likelihood ratio, P=0.027). Various factors were
      identified as barriers to HIV-VCT uptake; most of them were post test implicated.
      A number of factors that made some teachers to seek HIV-VCT services were also
      identified; HIV/AIDS awareness campaigns and urges 'to know status' were most
      cited factors. CONCLUSION: Although HIV-VCT utilization among secondary school
      teachers was higher than that of the general public, at 30.5% was still low.
      Various factors were found to influence HIV-VCT uptake

PMID- 23120934
TI  - Water quality analysis of the commercial boreholes in Mubi Metropolis, Adamawa
      State, Nigeria: geographic information system approach.
AB  - It is observed that most of the commercial boreholes in Mubi Metropolis are
      located along River Yedzeram which is the main river that runs across the town.
      Unfortunately, due to the geographical location of the town in savanna region
      with minimal water supply, water related small scale industries such as sachet
      water, block making, irrigation agriculture, cloth dying, car wash and other
      pollution activities such as mechanical workshops and public toilets are also
      located along the same River Yedzeram. Moreover, the inhabitants of the town
      either dump their refuse in the River or spread it on their farmlands as there is
      no provision of refuse dump site by the government. Therefore, five parameters
      (Nitrate, Magnesium, Copper, Calcium and Iron) were used to test thewater quality
      of water samples that were collected from twenty two commercial boreholes along
      the river, using the standard examination of water and waste water of the World
      Health Organization to determine the water quality of the boreholes. The study
      revealed that only eight out of the twenty two boreholes are of good quality,
      while the others are either of bad quality or not portable. ArcGIS 9.2 and ILWIS
      3.3 software were used to analyze the laboratory results through the use of SQL
      queries. It was recommended that the government should provide portable water,
      establish water quality control board and make use of GIS for creation of
      database and analysis.

PMID- 23120935
TI  - Dichlorodiphenyl trichloroethane (DDT) and its observed effects on body functions
      in vertebrates.
AB  - OBJECTIVE: To review research findings on the effects of DDT on body functions in
      vertebrates. METHODS: The research was based on retrieval and critical review of
      relevant articles and abstracts cited in international and regional journals. The
      literature search was done on MedLine from the year 1975 to 2010. The analyses of
      published data on various vertebrates (birds, fish, mice, human, among others)
      were considered. RESULTS: The effect of DDT on body functions is purely dependent
      on the degree of exposure. Whereas mild exposure (1-5mg/kg) may not have
      significant effects, very high concentrations (>100mg/kg) of DDT generally
      adversely affect the reproductive functions of animals. Eggshell quality, egg
      hatch-ability and health of chicks are affected by high DDT exposure. Very high
      DDT levels may increase the chances of spontaneous abortion and preterm birth,
      which is one of the main causes of infant mortality in humans. The health of a
      growing foetus and infant may also be compromised by DDT transfer from an exposed
      mother through the placenta and breast milk. The DDT affects the estrous cycle of
      exposed animals by altering the hormonal functions. In male rats, DDT has been
      observed to alter spermatogenesis and reduce aggression behaviour. However the
      effect in higher male animals has not been clearly elucidated. CONCLUSION: DDT
      exposure has drastic effects on reproductive functions in vertebrates, and safer
      alternatives should be considered rather than re-introducing DDT as a control
      agent for mosquitoes as has been suggested recently.

PMID- 23120936
TI  - Population prevalence of first- and second-degree family history of breast and
      ovarian cancer.
AB  - BACKGROUND: Family cancer history is an important risk factor for common cancers,
      thus, recognizing pattern of familial cancer can help us to identify individuals
      who may have higher chance to develop specified cancers. METHODS: This cross
      sectional survey assessed family history of cancer in first- and second degree
      relatives. Totally, 7,300 persons aged > or = 20 years selected by random
      sampling from Tehran general population. Age- and sex-specified prevalence of
      breast and ovarian cancer in respondent's family was calculated. RESULTS: Of all,
      279(4.3%) individuals reported a history of breast or ovarian cancer in their
      relatives. The prevalence of breast cancer family history was 1.8% among first
      degree relatives and 2.5% among second- degree relatives. For ovarian cancer,
      first- and second-degree prevalence ranged from 0.05 to 0.12%. Those with family
      history of cancer were more often young and female. CONCLUSIONS: Overall, the
      estimates of prevalence presented here are likely to be conservative compared
      with actual current prevalence because of some limitations. While family history
      is an important risk factor for common cancers such as breast cancer, recognizing
      pattern of familial cancer that signify increased risk can help us to identify
      individuals who may have higher chance to develop specified cancers.

PMID- 23120937
TI  - Perceived and actual cost of healthier foods versus their less healthy
      alternatives: a case study in a predominantly black urban township in South
      Africa.
AB  - OBJECTIVES: There is an increasing awareness of the role played by the food
      retail characteristics in determining individuals' healthy food purchasing and
      consumption behaviors. The perceived costs of healthier food alternatives have
      been shown to contribute negatively to individual's food choices in developed
      societies. However, there is still a dearth of knowledge regarding this
      phenomenon in low to middle income countries particularly in Africa. This study
      explored health club member's experiences in buying healthier food options and
      compared their perceived cost of selected healthier and less healthy foods with
      actual market costs in a South African township. METHOD: A cross-sectional study
      design using quantitative and qualitative research methods. The study was
      conducted in Khayelitsha, a township in the Western Cape Province in South
      Africa. Participants were 50 members of a health club, mostly female and above 50
      years of age. The study was conducted in three phases. The first phase involved
      interviews with all 50 health club members. During the second phase ten
      purposively selected members participated in in-depth interviews based on their
      unhealthy food-purchasing and consumption patterns identified in the first phase.
      The third phase involved food price audits from supermarkets as well as
      convenient stores located in the study setting. Quantitative data were subjected
      to descriptive statistical analysis, while content analysis was used to analyze
      qualitative data. RESULTS: Most of the members were illiterate and unemployed,
      largely dependent on government grants. Qualitative findings showed that low
      household incomes, their inability to read and interpret nutritional information
      and personal food preferences contributed to Health club members' unhealthy food
      purchasing behaviour. When objectively measured in local stores, the healthier
      food options proved to be more expensive than their less healthy equivalents.
      This was consistent with subjects' perceptions about the relative cost of the
      same foods in their local stores. CONCLUSION: Healthier foods tended to be more
      expensive than their less healthy options in local shops audited - both in
      reality and in the perceptions of health club members. Low income was reported to
      militate against health club members' healthy food-purchasing behaviour.

PMID- 23120938
TI  - The role of quality obstetric care services on reducing maternal mortality in
      rural areas of Tanzania.
AB  - This paper explores the role of quality obstetric care services on reducing
      maternal mortality in rural areas of Tanzania. Mgeta and Melela cascades located
      in Mvomero district, Morogoro region were used as case study. Tools for data
      collection involved combination of questionnaires and checklists, which were used
      to gather primary data from survey population. Purposive sampling method was used
      to select two health cascades and health facilities within Mgeta and Melela
      cascades. SPSS computer software and content analysis were respectively used to
      analyse quantitative and qualitative data. It was found in both health cascades
      that obstetric care services in health facilities were not well established and
      implemented. The study recommends that, special initiative should be done to
      bring changes on reducing maternal mortality, such as ensure essential equipments
      and medicines must be supplied constantly and maintained by skilled health staff
      who can manage both normal and complicated deliveries. Enforcement in providing
      quality of obstetric care services in maternal health services especially in
      rural areas where majority of people in Tanzania reside is not an overemphasis.

PMID- 23120939
TI  - A study on job satisfaction among clinical and non-clinical hospital staff in a
      teaching hospital in Lagos, Nigeria.
AB  - OBJECTIVES: Previous studies had demonstrated that continuous and effective
      productivity of hospital staff are linked to job satisfaction and only those who
      are satisfied with their job can be maximally effective and productive. This
      cross-sectional descriptive survey was designed to determine the levels of job
      satisfaction among various groups of health care professionals working in a
      teaching hospital in Lagos, Nigeria. METHODS: Two hundred clinical and non
      clinical hospital staff were invited to take part in the study. They completed a
      sociodemographic questionnaire and the Job Descriptive Index (JDI). RESULTS: The
      results indicated that majority clinical and non-clinical staff were satisfied
      with their jobs as regards the parameters of the JDI compared with those not
      satisfied with their jobs. CONCLUSION: The government and health policy makers
      should continue to pay attention to boost job morale and satisfaction of medical
      health workers to continue to make them to be satisfied with their job.

PMID- 23120940
TI  - Equity in access to health care provision under the medicare security for small
      scale entrepreneurs in Dar es Salaam.
AB  - The main objective of this study was to assess equity in access to health care
      provision under the Medicare Security for Small Scale Entrepreneurs (SSE).
      Methodological triangulation was used to an exploratory and randomized cross-
      sectional study in order to supplement information on the topic under
      investigation. Questionnaires were administered to 281 respondents and 6 Focus
      Group Discussions (FGDs) were held with males and females. Documentary review was
      also used. For quantitative aspect of the study, significant associations were
      measured using confidence intervals (95% CI) testing. Qualitative data were
      analyzed with assistance of Open code software. The results show that
      inequalities in access to health care services were found in respect to
      affordability of medical care costs, distance from home to health facilities,
      availability of drugs as well as medical equipments and supplies. As the result
      of existing inequalities some of clients were not satisfied with the provided
      health services. The study concludes by drawing policy and research implications
      of the findings.

PMID- 23120941
TI  - Epidemiology and histopathological features of esophageal cancer.
AB  - INTRODUCTION: Esophageal cancer is the 6th most common cause of cancer death in
      the world. During the past two decades some changes have occurred in histologic
      type and primary tumor location in some parts of the world but there is a little
      information about histopathological aspect of disease in Iran. The purpose of the
      present study was to clarify the features of histopathological of esophageal
      cancer in Iran. METHODS: This study designed as a cross sectional study. Data
      analysis was performed with descriptive and univariate methods. Information
      required for this study extracted from cancer registry forms. The cases were all
      patients who received a histopathological diagnosis of EC that were referred to
      this center from January 2003 to October 2008. RESULTS: A total of 264 EC cases
      were recruited in the study the lower third of the esophagus was the most
      frequent site of origin of these tumors. Squamus cell carcinoma was commonest
      histologic type of tumor. In 15.2% of cases tumor was metastasis to other organs.
      In 46.6% were in advanced stage at diagnosis. DISCUSSION: Based on result of
      present study, esophageal cancer in our country more presented in Squamus cell
      carcinoma histology type, in advanced stage. Since Squamus cell carcinoma have a
      poorer prognosis and given that these patients have vague symptomatology for
      approximately several months, therefore, early diagnosis and treatment led to
      better prognosis.

PMID- 23120942
TI  - Pneumocyctis pneumonia and pulmonary tuberculosis among HIV-infected patients at
      Muhimbili National Hospital, Tanzania.
AB  - BACKGROUND: Respiratory infections such as pulmonary tuberculosis (PTB) and
      pneumonia are significant causes of morbidity and mortality in HIV infection.
      Recent studies have shown an increase in Pneumocystis jerovecii pneumonia (PCP)
      in Sub-Saharan Africa. This study determines the prevalence of PCP and other
      pulmonary infections among HIV patients at HIV clinics in Tanzania. METHODS: HIV
      infected patients with cough were enrolled between May and November 2006. Sputum
      induction was done and examined for PCP using Toluidine blue stain and Polymerase
      chain reaction. Ziehl-Neelsen stain was also done for PTB. RESULTS: Nine of the
      125 (7.2%) had smear positive PTB. PCP was diagnosed in 10.4% (13/125) by
      Toluidine blue, while PCR was positive in 3.6% (3/88). Low CD4+ cell counts were
      associated with increased risk to both PCP and PTB. CONCLUSION: PCP is still low
      in Tanzania. PTB remains the major respiratory problem in HIV patients with
      cough. Toluidine blue staining is not reliable for PCP diagnosis

PMID- 23120943
TI  - Young adults and AIDS epidemics: their perception awareness information sources
      and sexual practices.
AB  - BACKGROUND: Education and awareness is important in appreciating the seriousness
      of a disease, and in arousing feeling of concern about an epidemic in any
      society. Continuing trend show a disproportionate increase in new incidences of
      HIV infection among young adults in sub-Sahara Africa. This study aimed to
      investigate a group of Nigerian student teachers' awareness and perception on
      AIDS, and their adherence to safe sex practices. METHODS: Nigerian students in a
      College of Education (N = 382) were surveyed using a 52-item questionnaire that
      solicited information on sociodemographics, knowledge on AIDS, and on how serious
      and concerned are the students about AIDS epidemic. It also elicited information
      on their information sources and needs, on AIDS testing, sexual activity, and
      condom use. RESULTS: The students showed satisfactory knowledge, and AIDS
      epidemics was a serious issue and of concern to them, but many of the students
      who had experience with sexual intercourse seldom use condom on a consistent
      basis. Level of perceived seriousness and feeling of concern about AIDS epidemics
      influenced condom use consistency, while male gender and knowledge level
      influenced the students' appreciation of the seriousness of AIDS epidemics. Male
      students reported experience with sexual intercourse and condom use more
      frequently than their female counterparts. CONCLUSION: The study affirms
      discrepancy between knowledge on AIDS and sexual practices and that an all
      inclusive approach to AIDS campaign including education and encounters that
      heightens the perception of seriousness and concern about AIDS epidemics could
      facilitate improved sexual practices and behavior among student teachers.

PMID- 23120944
TI  - Becoming pregnant during secondary school: findings from concurrent mixed methods
      research in Anambra State, Nigeria.
AB  - OBJECTIVES: Pregnancies among teenagers and problems associated with premarital
      births have raised concerns in many countries. It is important to explore
      unintended pregnancy from the viewpoints of local stakeholders such as students,
      schools/teachers, and community members. This study assessed reported cases of
      unintended pregnancy among students and perceptions of these pregnancies by
      members of the community. METHODS: This study took place in a rural community in
      Anambra state, southeastern Nigeria. A cross-sectional survey of 1,234 students
      and 46 teachers in five secondary schools was carried out using self-administered
      questionnaires. In addition, focus group discussions (FGD) involving 10 parents
      and in-depth interview (IDI) with a student who became pregnant were conducted.
      RESULTS: Reports of pregnancy were more common during second and third years of
      junior secondary school than other school years or level. According to teachers,
      ignorance was the main reason given by students who became pregnant. Students who
      became pregnant were reported to have performed poorly academically and lived
      with both parents, who were either subsistence farmers or petty traders. In the
      IDI, the ex-student opined that pregnant students faced shame, marital
      limitations and lack of respect from community members. Participants in the FGD
      suggested that teenagers should be provided with sex education in schools and in
      churches; parents should communicate with teenagers about sexual matters and make
      adequate financial provision; and the male partners should be held more
      accountable for the pregnancies. CONCLUSION: Poor sexual knowledge and poor
      socioeconomic conditions play important roles in teenage pregnancy. Male
      participation may enhance effectiveness of prevention programmes.

PMID- 23120945
TI  - Measuring patients satisfaction: a cross sectional study to improve quality of
      care at a tertiary care hospital.
AB  - OBJECTIVE: To measure the satisfaction of patients attending the OPD in SKIMS
      tertiary hospital of Soura, India. METHODS: Pre-structured questionnaire was
      framed and data collected from consenting patients attending the OPD of SKIMS
      hospital. The data were analyzed using SPSS version 12. SETTINGS: OPD section of
      SKIMS hospital, Soura, India. RESULTS: Four hundred (400) OPD patients were
      included in the study to know their perceptions towards the said hospital, reason
      for choosing the hospital, perception towards registration process, basic
      amenities and perception towards doctors and other staff. The major reason for
      choosing the health facility was skilled doctors. Majority of patients were
      satisfied with the facilities available as well as with the behaviour of doctors
      and other health staff. CONCLUSION: The health care delivered at this institute
      can be improved more and more once the organization, measures the delivery of
      quality of care on and ongoing basis and continually making small changes to
      improve the individual processes.

PMID- 23120946
TI  - HIV-related intimate partner violence among pregnant women in Nigeria.
AB  - AIM: To compare the prevalences and patterns of intimate partner violence between
      HIV-positive and HIV-negative pregnant women receiving prenatal care at a
      tertiary hospital in South East Nigeria METHODS: A comparative cross-sectional
      study of HIV-positive and HIV-negative pregnant women was done. Statistical
      analysis was by descriptive and inferential statistics at 95% level of confidence
      RESULTS: A total of 220 pregnant women studied. These were equally divided
      between HIV-positive women (cases) and HIV-negative women (controls). Cases did
      not differ significantly from controls with respect to age, parity, tribe,
      religion, marital status, monthly family income. HIV positive respondents
      experienced physical violence in the course of the index pregnancy six times more
      than controls; sexual violence about 4 times more than controls and were 12 times
      more likely to be denied sex by their partner compared to controls. Threat of
      being hurt, deprivation of financial support and denial of communication were the
      commonest forms of intimate partner violence among HIV-positive pregnant women
      and these also occurred significantly more among HIV positive women than the
      controls. CONCLUSION: HIV-positive status predisposes pregnant women to increased
      intimate partner violence more of emotional nature further underlying the
      enormity of social rejection suffered as a result of HIV infection. Intimate
      partner violence screening should form part of their routine antenatal care

PMID- 23120947
TI  - Social factors and lifestyle attributes associated with nutritional status of
      people living with HIV/AIDS attending care and treatment clinics in Ilala
      District, Dar Es Salaam.
AB  - OBJECTIVE: Tanzania is one of the countries that suffer huge burden of
      malnutrition and food poverty with over two million people living with HIV/AIDS.
      Despite ongoing nutritional interventions in care and treatment clinics for
      people living with HIV/AIDS (PLWHA), a high proportion of them still face
      nutritional problems, with about 29% being underweight. This study therefore
      aimed assessing social factors and lifestyle attributes associated with
      nutritional status among adults living with HIV/AIDS and attending care and
      treatment clinics (CTCs) in an urban district in Tanzania. METHODS: An interview
      schedule was administered to 412 randomly selected adult male and female clients
      attending different CTCs in Ilala district. Their anthropometric measurements
      i.e. body weights and heights were also taken. RESULTS: Findings revealed that
      18.4% of males and females were underweight according to their body mass indices.
      The risk of being underweight was higher among respondents who were young; who
      had never married; had no formal education as well as those who reported to be
      living with their families or friends, although these associations were not
      statistically significant. On the other hand, factors which had statistically
      significant association with nutritional status included the type of persons the
      client was living with and the habit of drinking alcohol. CONCLUSION: From the
      findings we conclude that PLWHA attending Care and Treatment Clinics in Ilala
      district, Dar es Salaam have problems with their nutrition with underweight being
      common among them. This suggests that the existing care and treatment clinics
      that provide nutritional support to PLWHA do not appear to address these issues
      in their totality. There is therefore, need to ensure that more efforts are
      geared towards providing nutritional counseling, support and encouragement of
      these clients within social contexts of their lives so in order for the current
      efforts to give best results.

PMID- 23120948
TI  - Sexual behavior and condom use among male students in Dar-Es-Salaam, Tanzania
      with emphasis on contact with barmaids.
AB  - OBJECTIVE: The objective of this quantitative study was to identifying factors
      that influence young men to participate in risky sexual behavior that place them
      at risk of HIV infection, as young people are at higher risk for HIV infection
      than adults. METHODS: A cross-sectional study design that employed face-to-face
      interview questionnaire to identify socio-demographic characteristics, sexual
      behavior, knowledge of HIV, STD, attitudes towards condoms was administered to
      175 sexually active male students between 17 and 24 years old in college settings
      of Dar-es-Salaam city, Tanzania. RESULTS: In the previous 12 months, 80% of
      students had at least one steady sex partner (girlfriend), 71% had sex with a
      barmaid, 33% had sex with a casual partner and 83% had multiple sex partners.
      Condoms had been used at some time by 83% of students, and in the latest sexual
      encounter by 56%. However, only 37%, 22%, and 11% consistently used condoms
      during sex with girlfriends, casual partners and barmaids, respectively. Condom
      use was least popular during sex with barmaids, and 94% and 91% of students had
      experienced oral and anal sex with barmaids, respectively. STD infection was
      reported by 42% of students. Sex with barmaids was associated with alcohol and
      illicit drug intake, sex under their respective influences, and STD infection.
      Despite the high prevalence of these risky behaviors, 64% of students replied
      that they were at low or no risk of HIV infection. CONCLUSION: Our findings
      suggest that HIV prevention programs for male students should emphasize risks
      associated with multiple sexual partners, and sex with barmaids and casual
      partners, to increase the risk perception of HIV/AIDS. Condom use needs to be
      promoted.

PMID- 23120949
TI  - Factors associated with willingness to accept a routine offer of HIV test in a
      large referral hospital in Western Kenya.
AB  - OBJECTIVE: Although Voluntary Counseling and Testing (VCT) has existed for more
      than 10 years, majority of Kenyans still do not know their HIV status, thus
      necessitating the introduction of other testing strategies to increase the number
      of people taking the test. The routine offer of an HIV test to all patients in
      health-care settings has been proposed to increase access to care. The main
      objective of this study was to identify factors associated with willingness to
      accept a routine offer of an HIV test. METHODS: This was a cross sectional study.
      The Setting was in the Outpatient department at a large Referral Hospital in
      Western Kenya. A total of 384 adult patients (both males and females) were
      recruited using systematic random sampling. Information was collected on basic
      socio demographic characteristics, knowledge about the routine offer of an HIV
      test, attitudes towards the testing and HIV testing practise. RESULTS: Of the 384
      respondents, 64.3% were unaware about the routine offer of HIV testing in Health
      facilities. Multivariate analysis identified the main predictors of willingness
      to accept an HIV test offered in hospital as the age (OR 3.7, C.I 0.068-1.075),
      level of education (OR 3.4, C.I 0.186-62.602), Knowledge about the routine HIV
      testing (OR 4.6,C.I 2.118-9.847), self-perception of HIV risk (OR 8.4,C.I 3.424
      20.496) and attitude towards routine offer of HIV testing (OR 9.2, C.I 0.042
      0.284). CONCLUSION: There is a need to come up with tailored training on the
      routine offer of an HIV test and devising strategies to address the main factors
      that influence the decision for patients to test as identified above.

PMID- 23120950
TI  - Diabetic foot lesions as seen in Nigerian teaching hospital: pattern and a simple
      classification.
AB  - BACKGROUND: Diabetic foot syndrome is a complication of diabetes mellitus that
      has serious socioeconomic implications for the individual, family and the society
      as a whole. When there are ulcers, the condition becomes limb threatening. Early
      detection of the risk factors and appropriate management of the ulcers reduces
      the incidence of amputations, morbidity and mortality. OBJECTIVE: To find the
      pattern of diabetic foot laesions (DFL) as seen at the orthopaedic clinic of
      Usmanu Danfodiyo University Teaching Hospital, Sokoto, Nigeria over a five-year
      period and to present a classification of DFL. MATERIALS AND METHODS: From June
      2006 to June 2011 diabetics who had complaints arising from their feet were
      referred to the orthopaedic clinic at Usmanu Danfodiyo University Teaching
      Hospital, Sokoto, Nigeria. At presentation each patient was examined and
      investigated. Each foot was examined thoroughly and all the laesions were
      documented and graded according to Wagner's classification. Out come of
      management of the cases of DFL was also recorded. All the data collected was
      analysed. RESULTS: Two groups (A and B) of patients were identified. In group (A)
      were patients in whom there was good renal function, no septicaemia, mean value
      of fasting blood glucose most often was < or = 14 mmol/l. In this group only the
      feet were threatened. There was a second group (B) in whom there was septicaemia,
      mean value of fasting blood glucose most often was < or = 15 mmol/l, and impaired
      renal function (ketone bodies were identified in urine, high serum levels of urea
      and creatine). Most of these patients had gangrene of the whole foot. In some of
      the patients infections extended into the gastrosnemius muscle. In diabetic foot
      laesions grades 0-3, no part of the foot was amputated. In diabetic foot laesions
      grade 4, infections were controlled and part of the foot had to be amputated. In
      diabetic foot laesions grade 5, infections were controlled with difficulty and
      there were systemic symptoms. Amputation of the whole foot was always indicated
      in this group of patients. The level of amputation most often was far above the
      ankle joint, either below or above knee. CONCLUSION: Outcome of treatment
      revealed three groups of feet. There were salvageable, difficult to salvage and
      unsalvageable feet. These three outcomes of treatment of diabetic foot lesions
      formed the basis of a new grading system: gradel (salvageable), grade 2
      (difficult to salvage) and grade 3 (unsalvageable). The condition of the patient
      determines the urgency, extent of intervention and length of stay in the
      hospital.

PMID- 23120951
TI  - Prevalence of Echinococcus granulosus in some selected sites of Ethiopia.
AB  - This study assesses the current prevalence status of Cystic echinococcosis in
      cattle and sheep and echinococcosis in dogs in Assela, Makale and Debre Zeit
      areas of Ethiopia. Our target areas represent three different agro-ecological
      zones in Ethiopia. Of the cattle studied the infected were, 17(13.4%) in Assela,
      20(23.3%) in Makale, and 3(10%) in Debre Zeit haboured at least one fertile
      Hydatid cyst. Among the sheep, 23(59%) haboured fertile cysts and no goat was
      found to have fertile cysts. There was a significant difference in the percentage
      of infected sheep with fertile cysts from the same group of cattle originating
      from the three study areas. The percentage fertility of the total cysts examined
      were 4.2%, 6.8% and 5.5% in Assela, Makale and Debre Zeit respectively. Out of
      this 56.5% was from Assela, 65.4%, Makale and 66.7% from Debre Zeit were viable.
      From the sheep examined, 43.6% had fertile cysts with viability of 90.7%. The
      lung was the most affected organ in both species. A total of 44 dogs, 14 from
      Assela, 15 from Makale, and 15 from Debre Zeit were examined for canine
      echinococcosis. The prevalence of the infection was 7(50%) in Assela, 3(20%) in
      Makale and 5(33.3%) in Debre Zeit. There was no significant difference between
      these prevalence rates although noticeable differences in the worm burdens among
      the three areas were observed.

PMID- 23120952
TI  - Effectiveness of routine antihelminthic treatment on anaemia in pregnancy in
      Rufiji District, Tanzania: a cluster randomised controlled trial.
AB  - OBJECTIVE: The aim of this study was to estimate the effect of an antihelminthic
      drug, given at booking and at term to antenatal care visits, on the prevalence of
      anaemia at term and 4 months post-partum in Rufiji district, Tanzania, the area
      with high prevalence of intestinal parasites. METHODS: A cluster randomised
      controlled trial was conducted on 3080 pregnant women. Out of these 1475 (study
      arm) received albendazole and 1605 (control arm) placebo. All women also received
      routine daily iron folate supplements (36 mg iron and 5 mg folate), and
      sulphadoxine pyramethamine (SP) to prevent malaria. Haemoglobin levels were
      assessed at booking, at term and 4 months post-partum. RESULTS: At term, median
      and mean haemoglobin level and the prevalence of severe (< 70 g/l) and moderate
      (70-104 g/l) anaemia did not differ. The reduction in the prevalence of anaemia
      from booking to term, was significantly larger in the study arm compared to
      control arm (26.1% vs. 18.8%; p < 0.001). At four months postpartum, mean
      haemoglobin was higher in the study arm compared to the control arm (118 vs. 113;
      p < 0.0001) while the reduction in proportion of women with anaemia (Hb <105
      g/dl) was significantly lower (30.6 vs. 21.2; p < 0.0001) in the study arm
      compared to the control arm. CONCLUSION: These findings support WHO's
      recommendation for anthelmintic treatment during pregnancy. However benefits for
      deworming may be limited in areas with an antenatal iron supplementation
      programme or low intensity of hookworm infections and hence future research
      should be directed towards the cost-effectiveness of the de-worming compared to
      other interventions for reducing anaemia in pregnancy.

PMID- 23120953
TI  - Cervical pre-malignant lesions in HIV infected women attending Care and Treatment
      Centre in a tertiary hospital, Dar es Salaam, Tanzania.
AB  - The aims of this study was to determine proportion of HIV infected women with
      cervical pre-malignant lesions; and compare the use of Visual Inspection of the
      cervix after application of Acetic acid (VIA) and Papanicolau (Pap) smear in
      screening for cervical premalignant lesions in HIV positive women attending Care
      and Treatment Centre (CTC) at Muhimbili National Hospital (MNH), Dar es Salaam,
      Tanzania. A total of 316 women aged 18-70 years had a Pap smear taken for
      cytology, followed by spraying onto the cervix with 4% acetic acid and then
      inspecting it. Cytology was considered negative when there was no Cervical
      Intraepithelial Neoplasia (CIN) lesion reported from the Pap smear taken, and
      positive if CIN lesion 1, 2 or 3 was reported. Detection of a well-defined,
      opaque acetowhite lesion close to the squamocolumnar junction or close to the
      external cervical os constituted a positive VIA. Out of 316 women, 132 women had
      acetowhite lesions on VIA, making the proportion of abnormal cervical lesions to
      be 42.4%. One hundred and one out of 312 women (32.4%) had CIN lesions detected
      on Pap smear. The proportion of agreement between these two tests was 0.3. The
      proportion of agreement was moderate in women with advanced WHO HIV clinical
      stage of the disease and in women not on ART (Anti Retroviral Therapy). Women
      with CD-4 count less than 200 cells/mm3 had more abnormal cervical lesions. There
      is considerable proportion of HIV positive women with premalignant lesions of the
      cervix. Considering the proportion of HIV women with abnormal lesions and the
      difficulty in logistics of doing Pap smear in low resource settings, these
      results supports the recommendation to introduce screening of premalignant
      lesions of the cervix using VIA to all HIV infected women.

PMID- 23120954
TI  - Quartz exposure and increased respiratory symptoms among coal mine workers in
      Tanzania.
AB  - Quartz has been an inevitable composition of different type of coal mined. The
      quartz exposures among coalmine workers has been attributed to activities such as
      cutting the adjacent rock, the roof, the floor and the intrusions. OBJECTIVE: The
      aim of the study is to determine the associations between quartz exposures and
      respiratory health in a labour intensive coal mine. METHODS: 239 randomly
      selected men participated in the study. A respiratory questionnaire was used,
      collected information and data were analysed by SPSS version 15. The criterion
      for significant association was 0.05 and below. RESULTS: Logistic regression
      controlling for age, smoking status and duration of employment showed a
      significantly increased odds ratio for breathlessness in the high exposed group
      (OR = 3.9 (95%CI: 1.4, 10.7). In addition there were significantly increased odds
      ratio in the highest cumulative quartz group for cough day and night (OR: 3.6),
      cough for four days or more in a week (OR: 6.7), cough with sputum in day and
      night (OR: 6.5) and dyspnoea (OR: 10.9) (Table 4). CONCLUSION: The results from
      this study provide important information for targeting prevention program for
      reducing exposure at mine workplace. Improvements in the work environment where
      exposures are higher than the TLV for respirable silica, ought to be performed.

PMID- 23120955
TI  - Effectiveness of incinerators in the management of medical wastes in hospitals
      within Eldoret municipality.
AB  - INTRODUCTION AND OBJECTIVES: Medical waste incinerators release into the air a
      host of pollutants that have serious adverse consequences on public health and
      the environment. This study aimed at determining the effectiveness of
      incinerators in Eldoret municipality in the management of medical wastes in
      relation to its maintenance and operation with an aim of giving recommendations
      towards reducing environmental pollution caused by emission of toxic pollutants
      and safeguarding the health of the incinerator operators as well as the
      surrounding communities. METHODOLOGY: A cross sectional study was carried out at
      three health facilities in Eldoret Municipality namely Moi Teaching and Referral
      Hospital blood Bank Transfusion Centre, Elgon View and Eldoret hospitals.
      Questionnaires, researcher observation and laboratory investigations of ash
      samples were used in data collection. The questionnaires were administered to all
      the personnel operating the incinerators. The ash samples collected were analyzed
      using Atomic Absorption Spectroscopy. RESULTS: The results showed that the
      incinerators were operated in substandard conditions due to breakdown of the
      ignition starter, lack of pollution control equipment, and a low combustion
      temperature. Laboratory investigation of the ash showed that the levels of the
      heavy metals tested were high compared to the national and international
      standards. Forty percent (40%) of the interviewees were aware of the health risks
      they were exposed to and used protective clothing and equipment. CONCLUSIONS:
      This study showed that the incinerators investigated are maintained and operated
      in substandard conditions. The ashes produced contain a wide range of toxic
      pollutants, including concentrated levels of a number of heavy metals. This poses
      serious environmental health and occupational safety hazard.

PMID- 23120956
TI  - Quality of health care and the need for assessment.
AB  - OBJECTIVE: In many hospitals of developing countries quality of care is below the
      expected standard to maintain patient safety. In 2006, health care experts from
      Tanzania and Germany collaborated on a set of indicators to be used as a hospital
      performance assessment tool. The aim of this study was to introduce this tool and
      check its feasibility for use in a Tanzanian regional hospital. METHODS: Within
      the hospital, independent observers assessed quantitatively structural quality
      and the performance of health care encounter using an itemized scale from 0 (0%)
      to 2 (100%) for each defined item. Outcome parameters were taken from the annual
      hospital report. In addition, semi-qualitative interviews with staff and patients
      were held to a) assess staff knowledge of the treatment guidelines published by
      the Tanzanian Ministry of Health and Social Welfare (MoHSW), b) assess attitudes
      and user motivation and c) authenticate the quantitative findings in a mixed
      method triangulation approach. RESULTS: Structural quality in maternity was at
      75% of the expected standard, while process quality ranged from 36% (Care of the
      newborn with APGAR score < 4) to 47% (normal delivery procedure). Staff knowledge
      ranged between 64% and 87% with low motivation and commitment given as
      contributing factors. Outcome (maternal mortality) was 481/100,000 live births
      with an infant mortality rate of 10%. DISCUSSION: The tool appeared to be
      feasible and effective in judging care quality. It provides a model for
      continuous quality improvement. Motivation of health care workers, a strong
      determinant of care process quality, might be improved by strengthening internal
      factors in health facilities. For conclusive validation, further studies using
      the tool must be conducted with larger numbers of institutions.

PMID- 23120957
TI  - Entrance surface dose of the common radiological investigations in Abuth, Zaria.
AB  - The entrance surface Dose (ESD) was determined among patients who presented for
      routine radiological examinations using thermoluminescent dosimeter (TLD) chips
      placed on averagely built adult [(30 cm) chest width, 60-90kg weight and 20
      40years)] by multiplying the incident dose/entrances dose by the back scattered
      factor [BSF] gotten from an experiment. The values obtained from ESD measurements
      are as follows 8.03 mGy for Abdomen, 0.13 mGy for chest AP, 0.69 mGy for chest
      lateral, 0.5 mGy for cervical spine; AP: 0.38 mGy for cervical spine lateral;
      4.75 mGy for hip AP: 12.83 mGy for hip lateral: 5.74mGy for lumbar spine, AP
      lumbar spine lateral is 15.15 mGy. 1.38m Gy is for pelvis AP. 2.93mGy for skull
      AP/PA 1.2mGy for skull lateral, 5.46mGy for thorax AP, while the lateral is
      14.90m Gy. The average dose value is 9.28mGy Range 0.13-14.90mGy (Percentage
      standard error; +/- 1.45). From this studies Radiation doses delivered for
      routine investigations are generally lower than IAEA reference doses. Using these
      values for optimization of radiation protection practices for patient should be
      ensured since it does not rule out options for stochastic radiation.

PMID- 23120958
TI  - Effect of health education on knowledge and oral hygiene practices of persons
      living with HIV in Nairobi, Kenya.
AB  - OBJECTIVE: To assess the effect of oral health education on knowledge and oral
      health seeking behaviour of persons living with HIV/AIDS (PLWHA). METHODS: Quasi
      experimental study design conducted among 195 Persons living with HIV/AIDS
      attending two Comprehensive Care Centres (CCC) at the Kenyatta National Hospital
      (intervention group) and Mbagathi district hospital (non-intervention group) in
      Nairobi Kenya. The participants were selected using systematic random sampling
      method and data collected using a questionnaire. Data was collected at baseline,
      at three months (review 1) and at six months (review 2). RESULTS: There was a
      significant change in oral health knowledge for KNH participants. However, no
      significant change in oral knowledge was recorded for MDH participants. The
      proportion of participants who brushed their teeth at least twice a day increased
      significantly from 52% to 88% for KNH. The proportion of those who had brushed
      the previous evening increased from 47% to 83.2%. There was no significant change
      in the proportion brushing at least twice a day among the non-intervention group.
      There was a significant association between change in knowledge and change to
      brushing at least twice a day among the intervention group. CONCLUSION: Oral
      health education led to improved oral health knowledge and oral hygiene practices
      among PLWHA.

PMID- 23120959
TI  - Levels of some micronutrients in some Nigerian hypertensives.
AB  - A total of seventy (70) consenting subjects were recruited for this study. The
      subjects consist of fifty (50) hypertensive subjects yet to receive treatment and
      twenty (20) normotensive (control) subjects. Subjects' blood pressure values were
      measured and serum was obtained from the whole blood collected by vene puncture
      using centrifugation technique. Serum calcium, phosphorus and magnesium were
      determined by established procedures using commercial kit reagents. Results show
      that the mean serum calcium, phosphorus and magnesium levels for hypertensive
      patients were 1.98 +/- 0.22 mmol/L, 1.65 +/- 0.42 mmol/L and 0.88 +/- 0.20 mmol/L
      as against 2.11 +/- 0.10 mmol/L, 1.50 +/- 0.12 mmol/L and 0.96 +/- 0.05 mmol/L
      for normotensive subjects. Fifty-four (54) percent and twelve (12) percent of the
      hypertensives had reduced calcium and magnesium levels respectively, but none for
      the normotensive subjects. Fifty-eight (58) percent of the hypertensive patients
      and forty-five (45) percent of the normotensives had elevated serum phosphorus
      levels, but no subject was hypophophataemic. Hypertension reduced serum calcium
      (P < 0.05) and magnesium (P > 0.05) levels among hypertensives in the south-south
      area of Nigeria. These micronutrients are therefore implicated in the progression
      of hypertension. These micronutrients are therefore implicated in the progression
      of hypertension. The effects of antihypertensive drugs and/or micronutrients'
      supplementation on blood pressure and serum calcium, phosphorous and magnesium
      levels in our study area should be further investigated. This is important
      because beneficial adjunct to the available modalities in the treatment of
      hypertension especially in Nigeria could be identified.

PMID- 23120960
TI  - Socio-economic status, urbanization, and cardiometabolic risk factors among
      middle-aged adults in Tanzania.
AB  - OBJECTIVE: This study was conducted to examine the associations between
      socioeconomic status, urbanization, and cardio-metabolic risk factors in
      Tanzania. METHODS: Participants were 209 adults (45-66 years) in Dar es Salaam,
      Tanzania. A structured questionnaire was used to evaluate socioeconomic status
      and behavioral characteristics, including income, education, occupation,
      residence (urban, rural, mixed), dietary factors, and smoking. Blood samples were
      collected and analyzed to measure lipid profiles and fasting glucose levels.
      Cardiometabolic risk factors were defined using World Health Organization
      criteria. RESULTS: Urban residence and higher socioeconomic status were
      associated with decreased intake of traditional staple food (ugali), and
      increased consumption of meat products and beverages. Higher socioeconomic status
      was associated with a significant 3.5-kg/m2 higher BMI (p = 0.0001) and 8 cm
      higher waist circumference (p < 0.001), and a three-fold increase in the risk of
      obesity. Urban residence was associated with poorer lipid profile, including
      significantly higher total cholesterol, increased LDL cholesterol, but lower
      triglycerides, compared to rural residence. The prevalence of metabolic syndrome
      was high (38%), and was associated with increased socioeconomic status.
      CONCLUSION: Urban residence and higher socioeconomic status were important
      correlates of cardiometabolic risk factors, including obesity and poorer lipid
      profile. Primary prevention and health screening strategies are needed to target
      cardiometabolic risk factors in urban areas, to reduce the burden of
      cardiovascular disease in Tanzania.

PMID- 23120961
TI  - Serum total anti-oxidant capacity of some Nigerian cigarette smokers.
AB  - Cigarette smoke has been reported to contain free radicals. The interaction of
      these free radicals with the body defense system and associated health risk among
      Nigerian smokers have remained scarcely investigated despite the high numbers of
      smokers in our society. This study thus, investigates the serum total antioxidant
      capacity of some Nigerian cigarette smokers in apparent good health and who have
      been smoking between 1.4 sticks of cigarette/day for about 1-3 years. Twenty(20)
      consenting smokers between 19 and 45 years consisting of fifteen (15) males and 5
      females were recruited after examination to certify their apparent good health.
      Twenty (20) non-smokers, who were matched in age and sex were included as control
      subjects. Serum total antioxidant capacity (TAC) was observed to be higher in
      male non-smokers (1.92 +/- 0.2 2mM) when compared with their female counterparts
      (1.88 +/- 0.16 mM). Among smokers, the males subjects showed a decreased TAC
      (Male: 1.45 +/- 0.23 mM and female; 1.65 +/- 0.16 mM) with a strong statistical
      difference between the TAC of smokers and non-smokers (t = 2.095, n = 20 and P <
      0.05). Data suggest lower oxidant defense and hence, increased susceptibility to
      free radical associated diseases especially among the male smokers. Conserted
      efforts need to be made by governmental agents to enforce legislation that could
      reduce the rate of smoking. Campaigns should also be initiated to educate the lay
      public on the dangers of cigarette smoking.

PMID- 23120962
TI  - Determinants of breastfeeding pattern among nursing mothers in Anambra State,
      Nigeria.
AB  - OBJECTIVES: The practice of optimal breastfeeding including exclusive
      breastfeeding for the first six months of life is still rare among nursing
      mothers despite numerous benefits of breastfeeding. This study was aimed at
      identifying the factors influencing breastfeeding pattern among nursing mothers
      in Anambra State, Nigeria. METHODS: A cross sectional study was carried out in
      three comprehensive health centres of Nnamdi Azikiwe University Teaching Hospital
      (NAUTH) located at Neni, Ukpo and Nnewi communities of Anambra State. A semi
      structured questionnaire was interviewer administered on 228 nursing mothers
      consecutively selected by a systematic random sampling method as they visited the
      maternal and child welfare clinics. In addition, four sessions of focus group
      discussions (one in each centre) involving 8-10 nursing mothers were held.
      RESULTS: Most mothers 190 (83.3%) were aged between 20 and 34 years. About 152
      (66.6%) had attended or completed secondary education and were mainly traders 86
      (37.7%) and full time house wives 66 (29.0%). Majority 208 (91.2%) had at least
      good knowledge of breastfeeding. Their main source of breastfeeding education was
      government health facilities (80.85%). Only 85 (37.3%) breastfed exclusively.
      Exclusively breastfeeding was significantly associated with maternal older age,
      parity, delivery at government facility, positive family attitude towards
      exclusive breastfeeding and breastfeeding education from government health
      facility (p < 0.05). Focus group discussion showed that mothers believed that
      adequate nutrition, physical, financial and emotional support to them would
      increase exclusive breastfeeding practice. CONCLUSION: Exclusive breastfeeding
      rate was low among the mothers and the factors identified to influence its
      practice have important implications to breastfeeding intervention programmes.
      Activities to promote exclusive breastfeeding should be focused on the group of
      women and location in which it was poorly practiced. In addition, support to the
      mothers would be necessary.

PMID- 23120963
TI  - Dysmenorrhoea and coping strategies among secondary school adolescents in Ilala
      District, Tanzania.
AB  - BACKGROUND: Dysmenorrhoea is common problem among adolescents worldwide. Its
      prevalence varies greatly in different populations and ethnic groups. Adolescents
      with severe dysmenorrhoea may miss classes and other social activities. The aim
      of this study was to determine the prevalence and coping strategies for
      dysmenorrhoea among secondary school adolescents in Ilala municipal, Tanzania.
      METHODS: A cross sectional study was conducted in eight public and private
      secondary schools in Ilala municipal. A total of 880 girls in form II and form
      III who had attained menarche were interviewed using a self administered
      questionnaire between August and October 2007. RESULTS: The mean age at menarche
      was 13.3 years with the youngest at nine years and the oldest at sixteen years.
      Six hundred fifty two (74.1%) girls had dysmenorrhoea. Backache, breast
      tenderness and non specific joint pains were significantly more common symtoms
      among adolescents with dysmenorrhoea than without dysmenorrhoea. Medication was
      used by 362 (55.5 %) girls to relieve dysmenorrhoea. Commonest medications used
      were paracetamol and diclofenac. Adolescents who missed school due to
      dysmenorrhoea were 154 (23.6%) and 140 (21.5%) missed social activities.
      CONCLUSIONS: High proportion of secondary school adolescents has dysmenorrhoea in
      Ilala municipal with a significant number missing school and social activities.
      Reproductive health education in primary and secondary schools should be enhanced
      to increase awareness and care seeking.

PMID- 23120964
TI  - [Pure dread].

PMID- 23120965
TI  - ["You cost too much! Now finally save!"].

PMID- 23120966
TI  - [With the DRG the sick body lost standardization (interview by Martina
      Camenzind)].

PMID- 23120967
TI  - [Case coordination becomes the key factor].

PMID- 23120968
TI  - [A world with no future].

PMID- 23120969
TI  - [With better health a longer career].

PMID- 23120970
TI  - ["ANP (advanced nursing practice) is especially for SPITEX an opportunity"
      (interview by Martina Camenzind)].

PMID- 23120971
TI  - [Stroke nursing: abruptly everything is different].

PMID- 23120972
TI  - [Blockade is resolved].

PMID- 23120973
TI  - [Maximized profit = quality at risk].

PMID- 23120974
TI  - [A complex reality].

PMID- 23120975
TI  - [Work must first be recognized!].

PMID- 23120976
TI  - [Mutual assistance today, tomorrow and every day...].

PMID- 23120977
TI  - [A subtle manual approach].

PMID- 23120978
TI  - [The standardized body].

PMID- 23120979
TI  - [Synthesis of melanin pigments by Antarctic black yeast].
AB  - Five strains of the black yeast similar to Exophiala nigra (Nadsoniela nigra),
      which we have isolated from the Antarctic biotopes, are studied. At cultivation
      in a periodic operation the maximum level of absolutely dry biomass in five
      tested strains constituted 3.2-7.8 g/l of medium, melanin pigment yield being 6
      9% of absolutely dry mass of cells. Two highly productive strains have been
      selected. Pigments of the studied black yeast are water-insoluble, however
      dissolve in alkali and concentrated acids. The maximum absorption of the yeast
      pigments was in the range of 220 nm. The above-stated properties of pigments of
      the investigated yeast correspond to the description of melanin fractions of
      Nadsoniela nigra and some microscopic mushrooms. The water-soluble melanin
      pigments have been obtained after the dialysis of alkaline solution of the
      pigment. UV-spectra and visible absorption spectra of water solution of melanin
      pigments are almost identical to those of initial alkaline solutions. It is shown
      that the studied yeast are resistant to high concentrations of toxic metals
      (Hg2+, Cu2+, Co2+, Cr(VI) and Ni2+), and introduction of Co2+ into the
      cultivation medium leads to the increase of pigments synthesis.

PMID- 23120980
TI  - [Isolation of Bacillus thuringiensis IMV B-7324 fibrinolytic peptidase].
AB  - Fibrinolytic peptidase of Bacillus thuringiensis IMV B-7324 was isolated by
      ammonium sulfate fractionation, gel-filtration and ion exchange chromatography on
      TSK-gels--Toyopearl HW-55 and DEAE 650 (M). Fibrinolytic activity of the purified
      enzyme was 87.9 U/mg of protein that was 19.9 times higher compared with the
      supernatant cultural liquid, the yield on its activity reached 31%. The gel
      filtration on Sepharose 6B and by SDS-PAGE electrophoresis demonstrated the
      homogeneity of the purified fibrinolytic peptidase, which molecular weight was
      approximately 24 kDa.

PMID- 23120981
TI  - [Serological characteristic of lipopolysaccharides of Ralstonia solanacearum].
AB  - By immunochemical investigations of eight strains of Ralstonia solanacearum six
      strains were attributed to four serogroups. Two of them are formed by pairs of R.
      solanacearum strains 4 and 526; 758 and 7954; two others are represented by
      single strains--TX1 Ta TS3, correspondingly. Antigenic structure of R.
      solanacearum 7954 O-polysaccharide unites antigenic epitopes of R. solanacearum
      strains 4, 35, 526, 749, however the absence of cross-reactivity does not permit
      uniting them into the same group. The latter, and also the fact that the
      antiserum to R. solanacearum 749 in the reaction with LPS of R solanacearum 526
      forms two precipitation lines (while in the homological system it forms only one
      line) may be explained by differences in the component composition of heat-stable
      immunogens (which were used for antiserum obtaining), and also purified LPS which
      were utilized as antigens in immunochemical reactions.

PMID- 23120982
TI  - [Influence of lactitol and lactulose on adhesion properties of Bacillus subtilis
      probiotic strains].
AB  - Adhesion properties of probiotic strains Bacillus subtilis UKM 5139 and Bacillus
      subtilis UKM 5140 is studied. It is shown that the strain Bacillus subtilis UKM
      5139 is nonadhesive, and the strain Bacillus subtilis UKM 5140 is subadhesive.
      Lactitol and lactulosa did not influence the adhesive properties of probiotic
      strains of bacilli, and reduced these properties of conditionally pathogenic
      microorganisms.

PMID- 23120983
TI  - [New aspects of the pleiotropic action of the genes coding Saccharomyces
      cerevisiae exopolyphosphatases].
AB  - Inactivation of the key genes, which are responsible for the enzymes of
      polyphosphates degradation, exopolyphosphatases ppx1 and ppn1, caused both an
      increase of polyphosphates content in Saccharomyces cerevisiae cells and an
      increase in chain length of acid-soluble and alkali-soluble fractions. It had no
      effect on the frequency of volutine granules metachromasy that was based on the
      interaction of dye molecules with ionic groups of polyphosphates. At the same
      time, a mutant strain reaction to nystatin differed from the reaction of the
      parental and wild-type strains when the metachromasy was absent. Obtained data
      may indicate a pleiotropic effect of ppx1 and ppn1 genes, which encode the major
      exopolyphosphatase of Saccharomyces cerevisiae and affect the reaction of cells
      to external factors through changes in the metabolism of polyphosphates.

PMID- 23120984
TI  - Antimicrobial activity of bifidobacterial bacteriocin-like substances.
AB  - Antagonistic activity of 13 bifidobacterial strains, isolated from humans, has
      been studied. It was shown that specific antagonistic activity in bifidobacteria
      is a strain characteristic and does not depend on species of these
      microorganisms. It was determined that bifidobacteria are able to produce
      bacteriocin-like substances against both gram-positive and gram-negative
      bacteria. Strains Bifidobacterium sp. 278 and B. bifidum 174 produced
      antimicrobial substances of wide spectrum of activity and manifested the highest
      antagonistic activity as compared to the rest of bifidobacterial strains studied.
      The maximal activity of bacteriocin production by strains B. bifidum 174 ma
      Bifidobacterium sp. 278 occurs between 8-16 hours of cultivation that is in the
      late logarithmic phase of growth. According to obtained characteristics the
      antimicrobial substances are complex peptides and belong to the 4th class of
      bacteriocins.

PMID- 23120985
TI  - [Reduction of chlorate in the presence of heavy metals by Acinetobacter
      thermotoleranticus C-1].
AB  - Influence of heavy metals on Acinetobacter thermotoleranticus C-1 was studied by
      the rate of chlorate reduction and biomass growth. It was established that Fe3+
      in a form of free ion at concentration of 30 mg/l also stimulates both the
      reduction of chlorate by A. thermotoleranticus C-1 and the growth of biomass,
      Cd2+ Pb2+ and Mn2+ do not practically affect the process velocity or stimulate it
      a little, Cu2+ and Zn2+ lower the reduction rate of C10(3)- 2.5-3 times, under
      these conditions the biomass growth is inhibited more weakly than the reduction
      rate. Nickel and cobalt in the mentioned amount inhibit completely the process of
      reduction. Metals in the form of hydroxide-ion proved to be less toxic for str. C
      1, than their ion forms. General influence of a free ion, metal hydroxide and the
      amount of organic nutrition takes more considerable (stimulating or inhibiting)
      influence on the process, than each of these factors itself.

PMID- 23120986
TI  - [Interrelations of infusoria with Azotobacter and their influence on plants].
AB  - Symbiotic coexistence of infusoria Colpoda steinii with bacteria of Azotobacter
      genus has been investigated. It is shown that when infusoria are incubated during
      3 days with the cells of A. vinelandii IMV D-7076 selected in the logarithmic
      phase of growth, the number of colpods increased 19 times, and with A. chrooccum
      20--only 1.8 times. After 6 days of incubation with bacteria selected in the
      phase of stationary growth the number of infusoria increased with A. vinelandii
      10 times, and with A. chrooccum 20 - 9.2 times. Treatment of seeds by the
      bacterial mix of A. vinelandii and C. stenii stimulates their germination, growth
      of roots and sprouts at early stages of plants development as compared with the
      use of cultures of monobacteria. It is evident that infusoria Colpoda steinii as
      well as the bacteria of Azotobacter genus secrete biologically active substances
      which accelerate growth and development of plants.

PMID- 23120987
TI  - [Geno- and phenotypic characteristic of Bacillus strains--components of
      endosporin].
AB  - Endosporin is used in veterinary for the prophylaxis and treatment of
      disbacteriosis, intestinal infections, festering wounds and postpartum
      pyoinflammatory complications in agricultural animals. The probiotic is based on
      two Bacillus strains which inhibit growth of a broad spectrum of pathogenic
      microorganisms and synthesise proteolytic enzymes and other biologically active
      secondary metabolites, particularly - polysaccharides. The activity of these two
      strains was supplementary. For the species identification of these strains,
      sequences of 16S rRNA genes and fatty acid content of cell walls were analysed.
      It was found that the both strains belong to B. velezensis. Limitations of
      application of 16S rRNA sequences for identification of closely related species
      are discussed in the paper. A method of 16S rRNA sequence profiling by
      polymorphic nucleotides was proposed. It was also shown that usefulness of
      Bacillus strains in probiotics is mostly based on their unique strain specific
      properties rather than on general species characteristics.

PMID- 23120988
TI  - Purification and structure elucidation of the by-product of new regulator of
      antibiotic production and differentiation of Streptomyces.
AB  - Streptomyces globisporus 1912, a producer of the antitumor antibiotic landomycin
      E, forms the new low-molecular signaling molecule N-methylphenylalanyl
      dehydrobutyrine diketopiperazine (BDD) and its complex and unstable by-product
      which restore, like the A-factor in Streptomyces griseus 773, landomycin E and
      streptomycin biosynthesis, and sporulation of the defective mutants S.
      globisporus 1912-B2 and S. griseus 1439, respectively. Here, we report the
      purification and structure elucidation of two compounds with R(f)0.8 by HPLC,
      LC/MS and 1HMR analysis. These compounds have m/z 338 and 384, accordingly, and
      each of them is presented by two stereoisomers containing BDD in their structure.
      A hypothesis explaining the composition and regulatory properties of these
      unstable compounds is presented.

PMID- 23120989
TI  - [Influence of bacteria of Bacillus genus on the causative agent of bacterial
      cancer of tomatoes].
AB  - It has been shown that bacteria of the genus Bacillus inhibited the development
      of infection caused by Clavibacter michiganensis subsp. michiganensis, in
      tomatoes. Pre-sowing seed treatment with suspensions of Bacillus subtilis IMV B
      7023 and Bacillus pumilus 3 enhanced resistance of plants to bacterial disease of
      cancer, probably due to the synthesis of biologically active substances with
      antimicrobial properties by these bacteria. Of the two strains of bacillus,
      differing by antagonist properties to C. michiganensis subsp. michiganensis, a
      significant stimulating effect on the growth and development of tomatoes was
      provided by the strain B. subtilis IMV B-7023, which is part of the bacterial
      preparations for crop production.

PMID- 23120990
TI  - Plasmid profile, colicinogeny and phage sensitivity as indicators of the dynamics
      of Escherichia coli populations in the human gut.
AB  - A possibility to use such bacterial phenotypes as plasmid profiles, colicinogeny
      and phage sensitivity as dynamics indicators of enterobacterial population in the
      human intestine was considered in the present work. All these three phenotypes,
      considered together with the type of enterobacterial association and age of the
      patients may reflect the dynamic state of the individual E. coli population that
      is currently prevailing in the intestinal microflora. The data on plasmid profile
      structure, colicinogeny and phage sensitivity indicate to considerable
      quantitative and qualitative diversity of E. coli genetic elements and the
      intensive interaction between bacteria in the human gut. This diversity is
      reflected on the formation of the dynamic population of intestinal bacteria,
      which obviously depends on the host age. The evaluation of the three above
      mentioned phenotypes confirmed that the E. coli isolates are closely coordinating
      with other members of the intestinal microbial association. It is noted that the
      plasmid frequency increases, the colicin range expands and phage sensitivity
      decreases in E. coli cells simultaneously with the increase of the number of
      enterobacterial species in the gut. The dynamics of changes in the biological
      features was observed among E. coli strains from different age groups of
      patients. The most significant was high frequency of colicinogenic strains in
      adult patients and di-associated E. coli containing one large plasmid in the
      youngest patients with dysbiosis.

PMID- 23120991
TI  - Graphical visualization of the biologically significant segments in the sequence
      sets of the relative plant viruses.
AB  - The author's and collaborators' computational investigations of the conserved
      biologically significant segments within viral nucleotide and amino acid
      sequences are considered in the article. The results obtained suggest that the
      interactive graphical visualization of the short identical or similar sites in
      the sequence sets of relative viruses allows to reveal various specific elements
      such as right, inverted tandem, opposite and regular repeals; deletion/insertion;
      GC/AT-rich sites; contexts of translation initiation and termination codons;
      transcription initiation signals; spontaneous nucleotide substitutions; codon
      usage bias etc. To reveal and investigate different biologically significant
      sequences very short and simple computer programs, based on common sequence
      scanning algorithm, may be employed. Various graphic objects, which appeared
      during visualization of similar sites, may be computationally converted into
      corresponding nucleotide or amino acid sequences followed by writing within a
      text file. The change of some scanning parameters or slight modification of
      certain program modules allows to enlarge the program potentialities. A set of
      little and simplified computer programs obtained by successive modifications of
      the initial program is a suitable tool for quick revealing and investigating
      various biologically significant sequence sites.

PMID- 23120992
TI  - The effect of lacto- and bifidobacteria compositions on the vaginal microflora in
      cases of intravaginal staphylococcosis.
AB  - The effect of intravaginal injection of Lactobacillus casei IMV B-7280,
      Lactobacillus acidophilus IMV B-7279, Bifidobacterium animalis VKL and
      Bifidobacterium animalis VKB strains in various compositions on the range of
      microflora of the urogenital tract on the model of experimental intravaginal
      staphylococcosis of mice was determined. It was established that under the
      influence of various compositions of these strains changes in microflora spectrum
      occurred: the number of representatives of normoflora increased and the number of
      pathogenic microorganisms, including staphylococci, streptococci, coliform
      bacteria and fungi, significantly decreased. It was determined that strains of
      lacto- and bifidobacteria, that were studied, are prospective components of
      future probiotic drugs efficient in treating staphylococcosis.

PMID- 23120993
TI  - [Sexual function after permanent seed implant prostate brachytherapy].
AB  - PURPOSE: The aim of this study was to evaluate the long-term effects of permanent
      seed implant prostate brachytherapy (BT) on sexual function (SF). MATERIALS AND
      METHODS: From September 2003 to July 2005, 56 patients underwent radical
      retropubic prostatectomy (RRP) without any hormone therapy, while 353 patients
      had undergone BT without any adjuvant hormone therapy in a single institute. Out
      of these 353 patients in the BT group, 305 patients received neoadjuvant hormone
      therapy (BT NHT + group), while 48 did not (BT NHT - group). SF was prospectively
      evaluated using the UCLA Prostate Cancer Index (UCLA-PCI). Potency was defined as
      the UCLA-PCI Q26 point of > or = 3. RESULT: The preimplant UCLA-PCI scores of SF
      for BT NHT - and BT NHT + groups were 50.9 and 13.4, respectively. The SF score
      of the NHT - group post operatively decreased to 38.9 within 6 months, but was
      maintained at the same level after that. With the recovery of the androgen, SF
      score of the NHT + group improved after BT: however, it did not reach up to that
      of the NHT - group. In the univariate analysis, patient's age was the only
      predictive factor for SF after BT. Thirty-four out of 48 patients in the BT NHT -
      group and 23 out of 56 patients in the RRP group showed adequate potency before
      surgery. Their 5-year potency preservation rate was 73.6% in the BT NHT - group
      and 4.3% in the RRP group. CONCLUSION: SF slightly decreased immediately after BT
      but was usually maintained during the course observation for 5 years. The 5-year
      SF preservation rate after BT was 73.6%.

PMID- 23120994
TI  - [Anastomotic stricture following radical retropubic prostatectomy: insights into
      incidence, management and factors predisposing for occurrence].
AB  - PURPOSE: Anastomotic stricture (AS) following radical prostatectomy (RP)
      decreases patients' quality of life. It occurs in 0.5% to 32% of men after open
      radical retropubic prostatectomy (RRP), although its etiology is poorly
      understood. In a series of patients who received RRP, we analyzed the incidence,
      possible predisposing factors, and management of AS after RP. MATERIALS &
      METHODS: Between April 1997 and March 2006, 129 consecutive patients underwent
      RRP in our hospital. Anastomosis between the bladder neck and urethra was
      performed with interrupted anastomosis using four 2-0 absorbable sutures. AS was
      diagnosed when a 16Fr. panendoscope could not be passed. We assessed the
      relationship between the management method for AS and time interval between the
      surgical procedure and diagnosis of the stricture. The relationships between
      comorbidities identified preoperatively (hypertension [HT], diabetes mellitus
      [DM], cardiovascular disease [CVD], cerebral infarction [CI] and smoking history)
      and the incidence of AS were determined. Risk factors, including age, body mass
      index [BMI], preoperative PSA, total prostate volume, operative time, blood loss,
      Foley duration, amount of stress urinary incontinence (SUI) per day, amount of
      drain output, pathological T stage, Gleason sum and surgical margin status were
      also assessed. RESULTS: The rate of AS after RRP was 10.9% (14/129). In 10
      patients (72%), AS occurred within 3 months of surgery, in 2 (14%) it occurred at
      4-12 months after surgery and in 2 (14%) more than 12 months after surgery. In
      univariate and multivariate analyses, intraoperative bleeding of 1,800 ml or more
      was independently the strongest predictor of AS. In two patients a urethral
      bougie was used and 11 underwent internal urethrotomy. Only 1 patient underwent
      transurethral resection. Of the 8 patients whose strictures were diagnosed within
      3 months after surgery and underwent internal urethrotomy, 6 had recurrent
      anastomotic strictures. CONCLUSIONS: Risk factors for AS are thought to be
      multifactorial. Intraoperative blood loss was significantly associated with the
      development of anastomotic stricture. We should understand that anastomotic
      stricture following radical retropubic prostatectomy is not a rare morbidity and
      should inform patients about the possibility of postoperative AS.

PMID- 23120995
TI  - [The intravesical recurrence after 3-day consecutive intravesical instillation of
      pirarubicine hydrochloride (THP) following transurethral resection of bladder
      tumor (TURBT) for non-muscle-invasive bladder cancer].
AB  - PURPOSE: We estimated the results of 3-day consecutive intravesical instillation
      of pirarubicine hydrochloride (THP) following transurethral resection of bladder
      tumor (TURBT) for non-muscle-invasive bladder cancer retrospectively. PATIENTS
      AND METHODS: Through March 1995 to April 2009, a total of 184 patients were
      instilled 3-day consecutive intravesical instillation of pirarubicine
      hydrochloride (THP) (30 mg/40 ml in disinfected distilled water) started within a
      few hours after TURBT. 184 patients were diagnosed as untreated fresh non-muscle
      invasive urothelial bladder cancer with no concomitant carcinoma in situ (CIS),
      no concurrent upper urinary tract urothelial cancer and no past history of upper
      urinary tract urothelial cancer. Number of tumors, tumor size, tumor grade and
      clinical tumor stage were analyzed in relation to tumor recurrence by univariate
      and multivariate analyses. Median follow-up were 55.1 months. RESULTS: Using EAU
      guideline on non-muscle invasive urothelial carcinoma of the bladder, 168
      patients were classified at intermediate risk of tumor recurrence, 14 patients
      were at low risk of tumor recurrence and 2 patients were at high risk of tumor
      recurrence. The shape of non-recurrence rate curve showed two phase decrease
      pattern, namely, early hasty decrease within 1.5 or two years and late gentle
      decrease thereafter. The 1, 2, 3, 5-year non-recurrence rate were 82.7%, 75.3%,
      72.3% and 67.4% respectively. The 3-year non-recurrence rate of low score group
      (recurrence score 1-3) at intermediate risk of tumor recurrence was 85.3%.
      Univariate analysis revealed that number of tumors, tumor grade and clinical
      tumor stage were related to tumor recurrence (p<0.05). By multivariate analysis,
      number of tumors and clinical tumor stage were related to tumor recurrence
      (p<0.05). CONCLUSIONS: In patients of low score group at intermediate risk of
      tumor recurrence without grade 3 urothelial carcinoma and concomitant bladder
      CIS, 3-day consecutive intravesical instillation of pirarubicine hyorochloride
      (THP) following TURBT for non-muscle-invasive bladder cancer would be a
      significant adjuvant therapy. But in patients of high score group at intermediate
      risk of tumor recurrence, it seemed better to do additional maintenance
      intravesical chemotherapy or intravesical BCG therapy.

PMID- 23120996
TI  - [Information tools utilized by outpatients presenting to a female urological
      clinic and their temporal trend: analysis of 3,480 patients].
AB  - OBJECTIVES: Female urological diseases, including pelvic organ prolapse and
      urinary incontinence, are common in elderly people, but public knowledge about
      these diseases is limited. We analyzed information tools that patients with
      female urological disease utilized to acquire information about their diseases.
      MATERIALS AND METHODS: This study included 3,480 patients who presented to our
      female urological clinic between January 2005 and December 2008. We conducted a
      questionnaire survey on what information tools were used for information
      gathering. RESULTS: The newspaper was the leading information tool (39.9%),
      followed by referral from another clinic (17.8%), internet (15.7%), TV (14.8%),
      recommendation by family or friends (5.5%), books or magazines (3.2%), and
      informative sessions for the public (0.6%). The temporal trend in the rate of
      information tool use over the 4 years showed that internet use increased
      significantly every year (p trend = 0.041) and was the most utilized tool in
      2008, along with referral from other clinics. The rate of newspaper or TV use
      depended on their volumes of the female urological diseases. Additionally, no
      change over the study period was observed for the rate of internet utilization
      for patients in their 40s or under; however, it increased in patients in their
      50s or over, and patients in their 50s and 60s utilized the internet as often as
      patients in their 40s or under in 2008. CONCLUSIONS: The newspaper was the most
      utilized information tool for patients with female urological diseases. However,
      internet use for gathering disease information is increasing, and the internet
      may be the most important information tool in the near future.

PMID- 23120997
TI  - [A case of advanced renal cell carcinoma with inferior vena cava thrombus treated
      with sunitinib as neoadjuvant therapy].
AB  - A 70 year old woman had a right renal tumor with vena cava thrombus up to right
      atrium. We started medical treatment with sunitinib at a dose of 50 mg as
      neoadjuvant therapy. In 2 months, the vena cava thrombus shrank to the same level
      of the diaphragm. After stopping sunitinib for 2 weeks, a nephrectomy and
      thrombectomy was performed with extracorporeal circulation. Pathological
      diagnosis was clear cell carcinoma, G2. The TNM stage was pT3bN0M0. There were no
      viable cells at the tip of the thrombus. There is no recurrence during 9 months
      after the operation. Although we had to stop medication due to thrombocytopenia,
      it was possible to continue to take sunitinib for 3 months and achieved the
      operation. Because of down-staging of the tumor thrombus, we didn't have to do
      thoracic surgery. These results suggest that neoadjuvant therapy with molecular
      target drug may reduce surgical invasion.

PMID- 23120998
TI  - [Rupture of the urinary bladder due to emphysematous cystitis: a case report].
AB  - We herein report a case of rupture of the urinary bladder due to emphysematous
      cystitis. The patient was an 77-year-old female who was hospitalized for
      treatment of a cerebral infarction and diabetes mellitus. Emphysematous cystitis
      was observed during examinations for fever. Despite urinary drainage and
      antibiotic therapy, she ran a fever for 3 weeks and had decreased urine volume.
      She was transferred to our hospital because a pelvic CT demonstrated intravesical
      gas, which suggested a diagnosis of a vesicorectal fistula. An emergency
      laparotomy was performed, and an extraperitoneal bladder rupture thus identified.
      She recovered under urinary drainage, ureterocutaneostomy, proper antibiotic
      therapy, and glycemic control. Although emphysematous cystitis is almost always
      cured with conservative therapy, an accurate diagnosis and proper treatment are
      required, because emphysematous cystitis may rarely result in the rupture of the
      urinary bladder.

PMID- 23120999
TI  - [A case of metastatic spermatic cord tumor from acute myelogenous leukemia].
AB  - A 60-year-old man with a history of acute myelogenous leukemia (AML) presented
      with a complaint of right groin mass. Three years ago the patient underwent an
      allogeneic bone marrow transplantation. Owing to successful engraftment,
      remission was achieved for three years. Radiological examinations showed tumor in
      the groin area along the right spermatic cord (diameter, 30 mm). Right high
      inguinal orchiectomy was performed. On preoperative tests, there was no other
      organ metastasis and no recurrence of AML. Pathological examination demonstrated
      an invasion of AML in the spermatic cord. It was considered that this case was an
      isolated extramedullary relapse of AML in the spermatic cord after allogeneic
      bone marrow transplantation. 21 months later, he is alive with no recurrence of
      AML. Isolated extramedullary relapses of AML after bone marrow transplantation
      has not been reported, it is possible that this is the first case of metastatic
      spermatic cord tumor from AML in Japan.

PMID- 23121000
TI  - [Segmental infarction of the testis diagnosed by MRI: a case report].
AB  - A 42 year-old male presented with right scrotal pain. Ultrasonography and color
      Doppler sonography revealed a segmental hypoechoic lesion with absent blood flow
      in the upper part of the right testis. MRI showed a well-defined avascular lesion
      with rim enhancement suggesting segmental infarction of the right testis. Scrotal
      pain was improved with conservative treatment, after which MRI revealed a
      reduction. Segmental infarction of the testis is extremely rare and is difficult
      to distinguish from testicular torsion and testicular tumor. MRI of the acute
      scrotum is considered to be important for avoiding unnecessary surgical
      treatment.

PMID- 23121001
TI  - [Solitary fibrous tumor of the urinary bladder: a case report].
AB  - Solitary fibrous tumor (SFT) is one of the mesenchymal tumor usually occurs in
      the pleura. Extrapleural occurrence of SFT is uncommon. We herein report an
      extremely rare case of 72-year old man with SFT originated in the urinary
      bladder. The tumor was incidentally discovered as a mass of 8.5 mm in diameter by
      a pelvic MRI. Cystoscopy revealed the protruding submucosal tumor in the center
      of the trigon. Transurethral resection was carried out. Pathological examination
      revealed a tumor composed of spindle cells with rich vascularity surrounded by
      abundant collagen fibers. The immunohistochemical findings showed a strong
      positivity to CD 34 and relatively weak positivity to Bcl-2. MIB-1 index
      indicated less than 3%, thus the tumor was diagnosed as a solitary fibrous tumor.
      The patient has no evidence of disease 16 months after the surgery. The current
      case was the first report in Japan and the twelfth worldwide.

PMID- 23121002
TI  - Obstetric outcome after intervention for severe fear of childbirth in nulliparous
      women - randomised trial.
AB  - OBJECTIVE: To compare the numbers of vaginal deliveries and delivery satisfaction
      among women with fear of childbirth randomised to either psychoeducation or
      conventional surveillance during pregnancy. DESIGN: Randomised controlled trial.
      SETTING: Maternity unit of Helsinki University Central Hospital. POPULATION: Fear
      of childbirth was screened during early pregnancy by the Wijma Delivery
      Expectancy Questionnaire (W-DEQ-A). Of 4575 screened nulliparous women, 371
      (8.1%) scored >= 100, showing severe fear of childbirth. METHODS: Women with W
      DEQ-A >= 100 were randomised to intervention (n = 131) (psychoeducative group
      therapy, six sessions during pregnancy and one after childbirth) or control (n =
      240) (care by community nurses and referral if necessary) groups. Obstetric data
      were collected from patient records and delivery satisfaction was examined by
      questionnaire. MAIN OUTCOME MEASURES: Delivery mode and satisfaction. RESULTS:
      Women randomised to the intervention group more often had spontaneous vaginal
      delivery (SVD) than did controls (63.4% versus 47.5%, P = 0.005) and fewer
      caesarean sections (CSs) (22.9% versus 32.5%, P = 0.05). SVD was more frequent
      and CSs were less frequent among those who actually participated in intervention
      (n = 90) compared with controls who had been referred to consultation (n = 106)
      (SVD: 65.6% versus 47.2%, P = 0.014; CS: 23.3% versus 38.7%, P = 0.031). Women in
      intervention more often had a very positive delivery experience (36.1% versus
      22.8%, P = 0.04, n = 219). CONCLUSIONS: To decrease the number of CSs,
      appropriate treatment for fear of childbirth is important. This study shows
      positive effects of psychoeducative group therapy in nulliparous women with
      severe fear of childbirth in terms of fewer CSs and more satisfactory delivery
      experiences relative to control women with a similar severe fear of childbirth.

PMID- 23121003
TI  - Prolonged atrial effective refractory periods in atrial fibrillation patients
      associated with structural heart disease or sinus node dysfunction compared with
      lone atrial fibrillation.
AB  - BACKGROUNDS: Atrial fibrillation (AF) is commonly associated with structural
      heart disease (SHD) or sinus node dysfunction (SND). We hypothesized that
      regional atrial effective refractory period (ERP) is different in patients with
      SHD/SND from lone AF. METHODS: We included 648 patients with AF (age, 56.0 +/-
      11.0 years; male, 77.3%; paroxysmal AF [PAF], 67.9%; persistent AF [PeAF], 32.1%)
      who underwent radiofrequency catheter ablation (RFCA), and compared the clinical
      characteristics in patients with SHD (n = 132) versus without SHD (n = 516) and
      those with SND (n = 74) versus without SND (n = 574). ERPs were measured at the
      high and low right atrium, proximal, and distal coronary sinus. RESULTS: (1)
      Patients with SHD had older age (P < 0.001), greater left atrial (LA) volume (P <
      0.001), LA pressure (P = 0.002), and plasma proatrial natriuretic peptide (P =
      0.005) than patients without SHD. (2) Patients with SND were older (P = 0.004),
      more likely female (P = 0.004), and had lower body weight (P < 0.001) and higher
      E/E' (P < 0.001) than those without SND. (3) The mean atrial ERP was
      significantly shorter in patients with PeAF than those with PAF (P < 0.001). The
      mean ERP was significantly longer in patients with AF with SHD/SND than those
      with lone AF (P = 0.006). (4) The clinical outcomes of RFCA were not
      significantly different between SHD/SND and lone AF for 14.8 +/- 8.5 months of
      follow-up period. CONCLUSION: The mean atrial ERP was shorter in patients with
      PeAF than those with PAF due to electrical remodeling. In contrast, AF patients
      with SHD/SND showed a more prolonged mean atrial ERP than those with lone AF,
      associated with LA enlargement or left ventricular diastolic dysfunction.

PMID- 23121004
TI  - Single-molecule DNA analysis reveals that yeast Hop1 protein promotes DNA folding
      and synapsis: implications for condensation of meiotic chromosomes.
AB  - During meiosis, long-range interaction between homologous chromosomes is thought
      to be crucial for homology recognition, exchange of DNA strands, and production
      of normal haploid gametes. However, little is known about the identity of the
      proteins involved and the actual molecular mechanism(s) by which chromosomes
      recognize and recombine with their appropriate homologous partners. Single
      molecule analyses have the potential to provide insights into our understanding
      of this fascinating and long-standing question. Using atomic force microscopy and
      magnetic tweezers techniques, we discovered that Hop1 protein, a key structural
      component of  Saccharomyces cerevisiae  synaptonemal complex, exhibits the
      ability to bridge noncontiguous DNA segments into intramolecular stem-loop
      structures in which the DNA segments appear to be fully synapsed within the
      filamentous protein stems. Additional evidence suggests that Hop1 folds DNA into
      rigid protein-DNA filaments and higher-order nucleoprotein structures.
      Importantly, Hop1 promotes robust intra- and intermolecular synapsis between
      double-stranded DNA molecules, suggesting that juxtaposition of DNA sequences may
      assist in strand exchange between homologues by recombination-associated
      proteins. Finally, the evidence from ensemble experiments is consistent with the
      notion that Hop1 causes rigidification of DNA molecules. These results provide
      the first direct evidence for long-range protein-mediated DNA-DNA synapsis,
      independent of crossover recombination, which is presumed to occur during meiotic
      recombination.

PMID- 23121005
TI  - Update: Cold weather injuries, active and reserve components, U.S. Armed Forces,
      July 2007-June 2012.
AB  - From July 2011 through June 2012, the number of active and reserve component
      service members treated for cold injuries (n=499) was lower than the number in
      each of the four previous one year periods. Over the last five years, frostbite
      was the most common type of cold injury in all the Services except for the Marine
      Corps, in which hypothermia was slightly more frequent. Service members who were
      female, less than 20 years old, or of black, non-Hispanic race/ethnicity tended
      to have higher cold injury rates than their respective counterparts. Army
      personnel accounted for the majority of cold injuries. Service members who train
      in and deploy to areas with wet and freezing conditions - and their supervisors
      at all levels - should be able to recognize the signs of cold injury and should
      know and implement the standard countermeasures against the threat of cold
      injury.

PMID- 23121006
TI  - Thyroid disorders among active component military members, U.S. Armed Forces,
      2002-2011.
AB  - During 2002-2011, among active component U.S. military members, the rates of
      idiopathic hypothyroidism were 39.7 and 7.8 per 10,000 person-years among females
      and males, respectively. Unadjusted rates of idiopathic hypothyroidism and
      chronic thyroiditis (e.g., Hashimoto's disease) were at least twice as high among
      white, non-Hispanic as black, non-Hispanic service members. However, black, non
      Hispanic service members had higher rates of goiter and thyrotoxicosis.
      Increasing rates of thyroid disorders during the period were accompanied by
      increases in numbers of screening tests for thyroid function recorded during
      outpatient visits. Increased thyroid function testing since the beginning of the
      wars in Iraq and Afghanistan may reflect increased testing of military members
      with mental disorders (e.g., depression, irritability, PTSD), musculoskeletal
      pain, sleep disorders, menstrual/fertility abnormalities, obesity, and other
      conditions which have sharply increased in prevalence over the same period.

PMID- 23121007
TI  - Reported vectorborne and zoonotic diseases, U.S. Air Force, 2000-2011.
AB  - During 2000-2011, U.S. Air Force Public Health Officers reported 770 cases of
      vectorborne and zoonotic diseases diagnosed at Air Force medical treatment
      facilities. Cases of Lyme disease accounted for 70 percent (n=538) of all cases
      and most cases of Lyme disease (57%) were reported from bases in the northeastern
      U.S. and in Germany. The annual numbers of reported Lyme disease cases were much
      higher during the last four years than earlier in the surveillance period. The
      next most commonly reported events were malaria (74 cases), Rocky Mountain
      spotted fever (RMSF) (41), Q fever (33), dengue (23), and leishmaniasis (20).
      These five infections and Lyme disease accounted for 95 percent of the reported
      conditions. Military service members accounted for a majority of the reported
      cases for most of the conditions, but family members and retirees accounted for
      most of the cases of Lyme disease and RMSF. Most reports of vectorborne and
      zoonotic diseases did not include mentions of recent travel.

PMID- 23121008
TI  - Reported vectorborne and zoonotic diseases, U.S. Army and U.S. Navy, 2000-2011.

PMID- 23121009
TI  - Surveillance snapshot: Influenza immunization among health care workers, August
      2002-April 2012.

PMID- 23121010
TI  - Construction and assembly of chimeric DNA: oligonucleotide hybrid molecules
      composed of parallel or antiparallel duplexes and tetrameric i-motifs.
AB  - Chimeric DNA containing parallel (ps) and antiparallel (aps) duplex elements as
      well as poly-dC tracts were designed and synthesized. Oligonucleotide duplexes
      with ps chain orientation containing reverse Watson-Crick dA-dT base pairs and
      short d(C)2 tails are stabilized under slightly acidic conditions by
      hemiprotonated dCH+-dC base pairs ("clamp" effect). Corresponding molecules with
      aps orientation containing Watson-Crick dA-dT base pairs do not show this
      phenomenon. Chimeric DNA with ps duplex elements and long d(C)5 tails at one or
      at both ends assemble to tetrameric i-motif structures. Molecules with two
      terminal d(C)5 tails form multimeric assemblies which have the potential to form
      nanoscopic scaffolds. A preorganization of the ps duplex chains stabilizes the i
      motif assemblies up to almost neutral conditions as evidenced by thermal melting
      and gel electrophoresis. Although, ps DNA is generally less stable than aps DNA,
      the aps duplexes contribute less to the stability of the i-motif than ps DNA.

PMID- 23121011
TI  - TP53 mutation is rare in primary myelofibrosis.

PMID- 23121012
TI  - Durable complete remission with abiraterone in castration resistant metastatic
      prostate cancer.

PMID- 23121013
TI  - High-level ab initio enthalpies of formation of 2,5-dimethylfuran, 2-methylfuran,
      and furan.
AB  - A high-level ab initio thermochemical technique, known as the Feller-Petersen
      Dixon method, is used to calculate the total atomization energies and hence the
      enthalpies of formation of 2,5-dimethylfuran, 2-methylfuran, and furan itself as
      a means of rationalizing significant discrepancies in the literature. In order to
      avoid extremely large standard coupled cluster theory calculations, the
      explicitly correlated CCSD(T)-F12b variation was used with basis sets up to cc
      pVQZ-F12. After extrapolating to the complete basis set limit and applying
      corrections for core/valence, scalar relativistic, and higher order effects, the
      final Delta(f)H degrees  (298.15 K) values, with the available experimental
      values in parentheses are furan -34.8 +/- 3 (-34.7 +/- 0.8), 2-methylfuran -80.3
      +/- 5 (-76.4 +/- 1.2), and 2,5-dimethylfuran -124.6 +/- 6 (-128.1 +/- 1.1) kJ
      mol(-1). The theoretical results exhibit a compelling internal consistency.

PMID- 23121014
TI  - Nuclear import of chromatin remodeler Isw1 is mediated by atypical bipartite cNLS
      and classical import pathway.
AB  - The protein Isw1 of Saccharomyces cerevisiae is an imitation-switch chromatin
      remodeling factor. We studied the mechanisms of its nuclear import and found that
      the nuclear localization signal (NLS) mediating the transport of Isw1 into the
      nucleus is located at the end of the C-terminus of the protein (aa1079-1105). We
      show that it is an atypical bipartite signal with an unconventional linker of 19
      aa (KRIR X(19)  KKAK) and the only nuclear targeting signal within the Isw1
      molecule. The efficiency of Isw1 nuclear import was found to be modulated by
      changes to the amino acid composition in the vicinity of the KRIR motif, but not
      by the linker length. Live-cell imaging of various karyopherin mutants and in
      vitro binding assays of Isw1NLS to importin-alpha revealed that the nuclear
      translocation of Isw1 is mediated by the classical import pathway. Analogous
      motifs to Isw1NLS are highly conserved in Isw1 homologues of other yeast species,
      and putative bipartite cNLS were identified in silico at the end of the C-termini
      of imitation switch (ISWI) proteins from higher eukaryotes. We suggest that the C
      termini of the ISWI family proteins play an important role in their nuclear
      import.

PMID- 23121015
TI  - The first collection of spacecraft-associated microorganisms: a public source for
      extremotolerant microorganisms from spacecraft assembly clean rooms.
AB  - For several reasons, spacecraft are constructed in so-called clean rooms.
      Particles could affect the function of spacecraft instruments, and for missions
      under planetary protection limitations, the biological contamination has to be
      restricted as much as possible. The proper maintenance of clean rooms includes,
      for instance, constant control of humidity and temperature, air filtering, and
      cleaning (disinfection) of the surfaces. The combination of these conditions
      creates an artificial, extreme biotope for microbial survival specialists: spore
      formers, autotrophs, multi-resistant, facultative, or even strictly anaerobic
      microorganisms have been detected in clean room habitats. Based on a diversity
      study of European and South-American spacecraft assembly clean rooms, the
      European Space Agency (ESA) has initialized and funded the creation of a public
      library of microbial isolates. Isolates from three different European clean
      rooms, as well as from the final assembly and launch facility in Kourou (French
      Guiana), have been phylogenetically analyzed and were lyophilized for long-term
      storage at the German Culture Collection facilities in Brunswick, Germany
      (Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen).
      The isolates were obtained by either following the standard protocol for the
      determination of bioburden on, and around, spacecraft or the use of alternative
      cultivation strategies. Currently, the database contains 298 bacterial strains.
      Fifty-nine strains are Gram-negative microorganisms, belonging to the alpha-,
      beta- and gamma-Proteobacteria. Representatives of the Gram-positive phyla
      Actinobacteria, Bacteroidetes/Chlorobi, and Firmicutes were subjected to the
      collection. Ninety-four isolates (21 different species) of the genus Bacillus
      were included in the ESA collection. This public collection of extremotolerant
      microbes, which are adapted to a complicated artificial biotope, provides a
      wonderful source for industry and research focused on very unusual properties of
      microbes. For ESA, this collection is an essential resource with which to
      evaluate the contamination potential of spacecraft-associated biology and
      validate new biological contamination control and reduction procedures.

PMID- 23121016
TI  - Where will curiosity take us?

PMID- 23121017
TI  - Alcohol and other drug use, club drug dependence and treatment seeking among
      lesbian, gay and bisexual young people in Sydney.
AB  - INTRODUCTION AND AIMS: Substance use and substance use problems are often more
      prevalent in same-sex attracted young people (SSAY), yet little to date has been
      published about substance use and problems in this population in Australia. This
      paper aimed to characterise patterns of alcohol use, club drug use and
      dependence, injecting drug use and engagement with treatment services, comparing
      lesbians, gay men, bisexual women and bisexual men. DESIGN AND METHODS: A cross
      sectional, online survey was conducted with 572 SSAY in Sydney, aged 18 to 25
      years. The Alcohol Use Disorders Identification Test--Consumption questions
      (AUDIT-C) assessed hazardous alcohol use, and the Severity of Dependence Scale
      assessed club drug dependence. RESULTS: Seventy per cent of respondents had AUDIT
      C scores indicative of hazardous alcohol use, and 29% of respondents had used
      club drugs in the previous 6 months. Multivariate logistic regression showed that
      male respondents had a lower odds of hazardous alcohol use (adjusted odds ratio =
      0.6, 95% confidence interval 0.4-0.9), but a higher odds of recent club drug use
      (adjusted odds ratio = 1.8, 95% confidence interval 1.2-2.7). Methamphetamine
      dependence was reported among half of respondents who reported use in the
      previous 6 months. Bisexual women were more likely than other respondents to have
      sought treatment for alcohol and other drug use, and overall treatment
      utilisation was low (6%). DISCUSSION AND CONCLUSIONS: This study reports high
      rates of drinking and club drug use, and a possible underutilisation of alcohol
      and other drug treatment. The findings suggest that SSAY in Sydney may be at a
      high risk of alcohol- and drug-related harm.

PMID- 23121018
TI  - Inner ear dysfunction in myotonic dystrophy type 1.
AB  - OBJECTIVES: Myotonic dystrophy type 1 is associated with various oculomotor,
      vestibular, and auditory abnormalities. However, auditory system investigation
      has been mainly performed with the subjective method of pure-tone audiometry. In
      this study, a detailed vestibular and audiological evaluation was undertaken,
      including the objective and more sensitive method of transiently evoked
      otoacoustic emissions (TEOAEs). MATERIALS AND METHODS: Twenty-four patients with
      genetically diagnosed myotonic dystrophy type 1 and 21 controls were studied.
      Audiological and vestibular investigations included pure-tone audiometry,
      tympanometry, auditory brainstem responses (ABRs), TEOAEs, and
      electronystagmography. RESULTS: Hearing impairment was evident in 15 (62.5%)
      patients and in nine of them (37.5%) ABR abnormalities were found. However,
      subclinical cochlear damage was found in all patients, as evidenced by absent
      emissions or lower otoacoustic emission amplitude. Vestibular hypesthesia was
      found in nine patients (37.5%), accompanied by spontaneous nystagmus in four of
      them (15.6%). CONCLUSIONS: Auditory and vestibular abnormalities are quite common
      in patients with myotonic dystrophy type 1. However, it appears that subclinical
      cochlear damage is an ubiquitous finding of the disease.

PMID- 23121019
TI  - Dietary patterns of children at 3.5 and 7 years of age: a New Zealand birth
      cohort study.
AB  - AIM: To describe the dietary patterns of children at 3.5 and 7 years born small
      for gestational age (SGA) and appropriate for gestational age (AGA) and the
      association of dietary patterns with socio-demographic and obstetric factors.
      METHODS: Children from a New Zealand birth cohort study were followed up at 3.5
      (n = 550) and 7 (n = 591) years. Dietary information was collected using a Food
      Frequency Questionnaire. RESULTS: Three dietary patterns were defined in these
      children ('traditional', 'junk' and 'healthy'). Factors associated with dietary
      patterns were examined in multivariable analyses. At 3.5 years, 'junk' was
      associated with maternal smoking in pregnancy, no attendance at antenatal
      classes, maternal BMI and a younger maternal age. At 3.5 years, 'healthy' was
      associated with being married when pregnant. At 7 years, 'traditional' was
      associated with being born SGA, smoking in pregnancy, a younger maternal age and
      being male. CONCLUSION: Maternal socio-demographic, obstetric factors and birth
      size were associated with dietary patterns. The associations were not consistent
      with each dietary pattern across age groups. To examine the impact of diet in
      childhood on growth and health outcomes, factors influencing dietary patterns
      should be assessed at regular intervals throughout childhood.

PMID- 23121020
TI  - Infinite copper(II) coordination architectures from a resonative aminotriazine
      derived tripodal ligand: synthesis, structures, and magnetic properties.
AB  - The ligand 2,4,6-tris(2-picolylamino)-1,3,5-triazine (o-H3tpat) with essentially
      resonative structure and two copper(II)-based one-dimensional coordination chain
      structures, [Cu3Cl5(o-H2tpat)(H2O)].MeOH.CH2Cl2 (1) and [Cu2(o
      H2tpat)(H2O)(MeOH)(NO3)2](NO3).3MeOH (2), with different structural patterns have
      been synthesized and characterized using single crystal X-ray diffraction
      analysis. For o-H3tpat, two crystalline forms showing different solid-state
      structural features are obtained from MeOH/Et2O (form I) and CH2Cl2/Et2O (form
      II), respectively. The o-H3tpat form I adopts an asymmetric-configured all-amino
      resonative tautomer with three cis-trans-trans-arranged pyridyl groups, whereas
      the o-H3tpat form II adopts also an identical resonative structure but where two
      of the three pyridyl groups are in a cis-manner and the third one is nearly
      coplanar with the central aminotriazine core. On the other hand, the designed
      tripodal ligand in both Cu(II)-complexes serves as a monoanion, o-H2tpat(-),
      which suits a propeller-configured all-imino resonative structure in 1 and a syn
      anti-configured amino-imino-imino resonative structure in 2. These observations
      significantly indicate that the o-H3tpat ligand can self-adjust and interconvert
      its conformation via a possible structure transformation associated with proton
      shift to adapt a change in the crystallization and self-assembly reaction
      systems. In the magnetic point of view, 1 is treated as repeated chains composed
      of infinite {Cu6Cl10} units wherein the hexanuclear unit is further decomposed to
      one {Cu(II)4Cl6} and two magnetically isolated {Cu(II)Cl2} subunits.
      Antiferromagnetic interactions are found for the Cu4 subunits (g = 2.33, 2J1 = 
      5.6 cm(-1), 2J2 = -8.6 cm(-1), 2J3 = -4.1 cm(-1), and J4 held to zero). For 2, it
      is considered as an infinite chain that composes of Cu2 units
      antiferromagnetically coupled (g = 2.03, 2J1 = -0.2 cm(-1)). The small
      antiferromagnetic exchange constants in both 1 and 2 suggest that the unpaired
      spins do not effectively interact through the tripodal o-H2tpat(-) ligands. 

PMID- 23121021
TI  - Role of sex steroids, intrahepatic fat and liver enzymes in the association
      between SHBG and metabolic features.
AB  - BACKGROUND: SHBG and liver enzymes levels are both associated with the risk of
      type 2 diabetes. However, the relationship between SHBG with liver enzymes and
      intrahepatic fat content remain poorly understood. OBJECTIVE: To investigate
      whether SHBG is correlated with glucose and lipids levels and whether this
      association depends on fatty liver content, liver enzymes or sex hormone
      concentrations. DESIGN AND PATIENTS: We studied 233 dysmetabolic men with
      measures of plasma SHBG, total testosterone, 17beta-oestradiol, glucose,
      adiponectin, liver enzymes and hepatokines. Intrahepatic liver fat and visceral
      fat contents were measured by magnetic resonance imaging in 108 of these
      individuals. RESULTS: After adjustment for age, SHBG concentration was inversely
      correlated with fasting glucose (betastandardized  = -0.21, P = 0.0007), HbA1c
      (betastandardized  = -0.27, P < 0.0001), triglycerides (betastandardized  = 
      0.19, P = 0.003) and positively correlated with HDL-Cholesterol (betastandardized
      = 0.14, P = 0.03). These correlations persisted after adjustment for either
      total testosterone or 17beta-oestradiol levels. SHBG was not related to either
      fetuin A or FGF 21 concentrations. The inverse association of SHBG with HbA1c and
      glycaemia was not altered after adjusting for liver markers but was no longer
      significant after adjustment for hepatic fat content. CONCLUSION: The significant
      association between SHBG and fasting glycaemia, HbA1c and lipid levels in
      dysmetabolic men was not related to either sex hormones or markers of liver
      function, but was dependent on intrahepatic fat. This suggests that intrahepatic
      fat, but not alterations in liver function markers, may be involved in the
      association between SHBG and glucose and lipid metabolism.

PMID- 23121022
TI  - Over-expression of heat shock factor 1 phenocopies the effect of chronic
      inhibition of TOR by rapamycin and is sufficient to ameliorate Alzheimer's-like
      deficits in mice modeling the disease.
AB  - Rapamycin, an inhibitor of target-of-rapamycin, extends lifespan in mice,
      possibly by delaying aging. We recently showed that rapamycin halts the
      progression of Alzheimer's (AD)-like deficits, reduces amyloid-beta (Abeta) and
      induces autophagy in the human amyloid precursor protein (PDAPP) mouse model. To
      delineate the mechanisms by which chronic rapamycin delays AD we determined
      proteomic signatures in brains of control- and rapamycin-treated PDAPP mice.
      Proteins with reported chaperone-like activity were overrepresented among
      proteins up-regulated in rapamycin-fed PDAPP mice and the master regulator of the
      heat-shock response, heat-shock factor 1, was activated. This was accompanied by
      the up-regulation of classical chaperones/heat shock proteins (HSPs) in brains of
      rapamycin-fed PDAPP mice. The abundance of most HSP mRNAs except for alpha B
      crystallin, however, was unchanged, and the cap-dependent translation inhibitor
      4E-BP was active, suggesting that increased expression of HSPs and proteins with
      chaperone activity may result from preferential translation of pre-existing mRNAs
      as a consequence of inhibition of cap-dependent translation. The effects of
      rapamycin on the reduction of Abeta, up-regulation of chaperones, and
      amelioration of AD-like cognitive deficits were recapitulated by transgenic over
      expression of heat-shock factor 1 in PDAPP mice. These results suggest that, in
      addition to inducing autophagy, rapamycin preserves proteostasis by increasing
      chaperones. We propose that the failure of proteostasis associated with aging may
      be a key event enabling AD, and that chronic inhibition of target-of-rapamycin
      may delay AD by maintaining proteostasis in brain. Read the Editorial Highlight
      for this article on doi: 10.1111/jnc.12098.

PMID- 23121023
TI  - Shiga toxin-producing Escherichia coli from raw milk cheese in Egypt: prevalence,
      molecular characterization and survival to stress conditions.
AB  - Raw milk cheese is considered as a risk for foodborne Shiga toxin-producing E.
      coli (STEC) contamination. In this study, 124 raw milk cheese samples (64 Kareish
      and 60 Damietta cheese samples) were assayed for the presence of STEC using
      molecular detection of virulence markers such as Shiga toxins (stx1 and st*2) and
      intimin gene (eae) and by serotyping. By PCR, 14 E. coli strains showed the
      presence of the stx2 gene, either single or in association with the stx1, and
      were considered positive for STEC. The isolated non-O157 STEC in this study (from
      serotypes O22:H8, O26:H11, O86:H21, O103:H2, O113:H21 and O146:H21) were
      inoculated in 10% skim milk and were compared to O157:H7 reference strain for
      their survival under different stress conditions (pH levels between 4.5 and 6.5
      and salt concentrations between 1 and 6%) and 8 days of storage at refrigeration
      temperature (4 degrees C). Strikingly, our results showed that O26:H11 survived
      significantly better than O157:H7 under acidic pH and higher salt concentration.

PMID- 23121024
TI  - The role of next of kin of patients with cancer: learning to navigate
      unpredictable caregiving situations.
AB  - AIMS AND OBJECTIVES: The aims of this study are to develop knowledge about (1)
      the experiences of next of kin in caring for seriously ill patients with cancer
      and (2) the effects of strain and support on the next of kin's ability to cope.
      BACKGROUND: Better treatment has resulted in patients with cancer normally living
      longer. Because this treatment is typically administered in a polyclinic or at
      home, next of kin inherit the largely unknown and demanding role of caregiver.
      DESIGN: A qualitative, descriptive and interpretive design. METHODS: Focus group
      interviews were used. The sample comprised 16 adults who were the next of kin of
      patients with cancer. A thematic content analysis was performed, the text coded
      for meaning units, condensed and interpreted based on the understanding of the
      next of kin's role and ability to handle the situation. RESULTS: The role of next
      of kin is multifaceted and challenging. It is important for next of kin to be
      near and to take care of the sick. Next of kin's acceptance of the situation
      plays a crucial role in their ability to cope and to look forward. The
      unpredictability of the situation adds stress and affects the daily routines.
      CONCLUSIONS: Providing next of kin with knowledge, support and guidance is
      important in helping them to understand and cope with the situation and to reduce
      the amount of strain that they experience in the caregiving role. RELEVANCE TO
      CLINICAL PRACTICE: This study emphasises the importance of health workers in
      possessing the knowledge and competence required to educate, guide and support
      the next of kin of those with cancer. Health workers should provide care to next
      of kin, and a support system for next of kin must also be available.

PMID- 23121025
TI  - Cross-sectional epidemiological survey of asthma in Jinan, China.
AB  - BACKGROUND AND OBJECTIVE: The prevalence and control of asthma in all ages are
      seldom known in Jinan, China. This study aims to determine the prevalence,
      related factors and control of asthma in populations of all ages in Jinan, China.
      METHODS: A cross-sectional epidemiological questionnaire survey was performed
      with all members from approximately 4500 randomly selected families from 60
      communities in the urban area and in 40 villages in the rural area. The completed
      questionnaires were focused on asthma, asthma-like respiratory symptoms and
      asthma control. RESULTS: A total of 13,645 individuals were interviewed in the
      survey, and the number of effective questionnaires reached 13,419. The asthma
      prevalence of all ages in Jinan was 1.1%. Atopy, asthma family history, household
      size and age were independent factors related to asthma. The control of asthma in
      Jinan was suboptimal in a high proportion of patients and even worse in the rural
      area. CONCLUSIONS: The asthma prevalence for all ages in Jinan was relatively low
      compared with that in western countries; however, local asthma control fell
      markedly short from the goals of the Global Initiative for Asthma (GINA) criteria
      for asthma management, which may be attributed to the poor adherence to GINA
      guidelines, especially the underuse of preventative medication of inhaled
      corticosteroids.

PMID- 23121026
TI  - [Pleomorphic adenoma of salivary glands: diagnostic pitfalls and mimickers of
      malignancy].
AB  - Pleomorphic adenoma is the most common salivary gland tumor, characterized by a
      complex biphasic proliferation of epithelial and myoepithelial cells intermingled
      with a mezenchymal component with frequent metaplastic changes and protean
      histomorphology of the cells. This review describes several unusual histological
      findings in pleomorphic adenoma that may mimic malignancy, and therefore they
      represent a diagnostic pitfall. Intravascular invasion of tumor cells is
      generally suspicious of malignancy; however, intravascular tumor deposits may be
      rarely found within the capsule of clinically benign salivary pleomorphic
      adenomas. It is important not to render a malignant diagnosis in such neoplasms,
      in the absence of other evidence of malignancy. Pleomorphic adenomas,
      particularly of minor glands of palate, may contain large areas of squamous and
      mucinous metaplasia suspicious of mucoepidermoid carcinoma (MEC). In contrast to
      MEC, metaplastic pleomorphic adenomas do not harbour the distinctive
      translocations t(11;19) and t(11;15), they are not invasive, in contrast they
      reveal at least focally myxochondroid stroma. Cribriform structures in
      pleomorphic adenoma may mimic adenoid cystic carcinoma. Oncocytic metaplasia in
      cellular rich pleomorphic adenoma/myoepithelioma may be associated with
      significant nuclear polymorphism and hyperchromasia suspicious of malignancy. The
      most common pitfall in diagnosis of pleomorphic adenoma is so called "atypical
      PA" that must be distinguished from early malignant transformation to in situ
      carcinoma ex pleomorphic adenoma.

PMID- 23121027
TI  - [Pseudotumors of the central nervous system].
AB  - The histopathological differentiation of the pseudoneoplastic lesions from the
      tumors of the central nervous system (CNS) is not easy in a proportion of cases
      and the risk of diagnostic misinterpretation in biopsies of the CNS remains
      relatively high. Here we discuss selected CNS lesions, which can be easily
      mistaken for a tumor, particularly in the absence of relevant clinical and
      neuroradiological data - gliosis, tumefactive demyelination, radionecrosis and
      focal cortical dysplasia. With the exception of the recently available IDH1
      immunohistochemistry, there is a lack of simple and reliable histochemical or
      molecular markers which could facilitate this differential diagnosis. To avoid a
      diagnostic error, pathologists have to rely on careful microscopic analysis along
      with its correlation with clinical data and neuroradiological findings.

PMID- 23121028
TI  - Pseudotumors and mimickers of malignancy  of the head and neck pathology.
AB  - We are summarizing some of the difficult pitfalls in tumors of the head and neck,
      which we have encountered in our biopsies referred for consultation as well as
      from our routine praxis in the last 20 years. Shortly we are presenting the
      following lesions of head and neck: multifocal sclerosing thyroiditis,
      mucoepidermoid carcinoma of the thyroid, solid cell nests, Chievitz organ,
      rhomboid glossitis, ectopic parathyroid, signet ring cell change of salivary
      glands, mucocele, epithelial misplacement of the vocal cord squamous cell
      epithelium, and angiomatoid nasal polyps.

PMID- 23121029
TI  - [Histiocytic necrotizing lymphadenitis / Kikuchi-Fujimoto disease (HNL/K-F)  and
      its differential diagnosis: analysis of 19 patients].
AB  - Histiocytic necrotizing lymphadenitis / Kikuchi-Fujimoto disease (HNL/K-F) is
      being recognized with an increasing frequency not only in the East Asia but also
      on the American continents and in the Europe. Still the diagnostics of HNL/K-F is
      not easy and difficulties with its proper classification persist. In a group of
      19 patients diagnosed primarily or as consults at our department there were 12
      woman and 7 men. An average age at diagnosis was 28 years, median 25 years.
      Cervical lymph nodes were involved in 18 patients. Bilateral lymphadenopathy was
      present in one patient, the remaining 17 were unilateral. Inguinal lymph node was
      affected in one patient. In one other patient there were enlarged retroperitoneal
      lymph nodes simultaneously with a cervical lymphadenopathy. The size of the lymph
      nodes varied between 5 mm to 32 mm. The subclassification showed the necrotizing
      type in 14 patients, in one there was a predominant xanthomatous tissue reaction
      around the necrotic areas (xanthomatous type), and in 4 patients the disease was
      recognized as the proliferative type without necrosis (in two with a variously
      intense apoptosis of the proliferating lymphocytes). Of 10 consult cases the
      tumor was primarily evaluated as B cell lymphoma not otherwise specified (1x),
      peripheral T cell lymphoma (1x), classical Hodgkin lymphoma of mixed cellularity
      (1x); two patients were submitted with a differential diagnosis between
      peripheral T cell lymphoma and HNL/K-F; in one diagnosis of probable EBV
      lymphadenitis and in one diagnosis HNL/K-F was made. There were no data submitted
      in the remaining three cases. The authors stress diagnostic features which should
      lead to the diagnosis of the disease and should prevent unnecessary oncological
      staging investigations and potential chemotherapy for a lymphoma. Among
      diagnostic features of HNL/K-F identification of the proliferating cells - CD8
      activated lymphocytes with apoptotic decay prevail, there are frequent
      plasmacytoid monocytes and a striking reaction of macrophages which are
      CD68/myeloperoxidase positive. There are virtually no neutrophil granulocytes and
      there is a miminal participation of plasma cells. In case of necrotizing and
      xanthomatous type infectious causes are to be ruled out as well. In case we still
      need to distinguish HNL/K-F from a lymphoma PCR analysis of a rearrangement of
      the immunoreceptor gene in T cell population should be investigated.

PMID- 23121030
TI  - Gliosarcoma with alveolar rhabdomyosarcoma-like component: report of a case with
      a hitherto undescribed sarcomatous component.
AB  - Gliosarcoma (GS) is a relatively rare glioblastoma variant characterized by
      biphasic glial and mesenchymal differentiation patterns. The sarcomatous part
      most commonly resembles fibrosarcoma or so-called malignant fibrous histiocytoma.
      Rarely, GS shows heterologous lines of differentiation in the form of
      osteosarcoma, chondrosarcoma, liposarcoma, leiomyosarcoma, squamous or glandular
      malignant epithelial differentiation, or primitive neuroectodermal tumor (PNET)
      like foci. When rhabdomyoblastic differentiation occurs, it is in the form of
      malignant spindle cells, with cross-striated strap cells or rounded
      rhabdomyoblasts reminiscent of the embryonal type of rhabdomyosarcoma. We are
      reporting a case of GS with an alveolar rhabdomyosarcoma-like component. The
      tumor consisted of poorly differentiated primitive small round cells growing in a
      solid and alveolar pattern, with minimal cytoplasm, markedly elevated mitotic
      activity and numerous apoptotic nuclei. Rhabdomyosarcomatous differentiation was
      confirmed by desmin and myogenin immunopositivity. To the best of our knowledge,
      this histologic pattern has not been previously reported in GS. Differential
      diagnostic considerations are discussed. KEYWORDS: gliosarcoma - alveolar
      rhabdomyosarcoma - myogenin - desmin.

PMID- 23121031
TI  - Perineural cell differentiation in ganglioneuromas.  Report of 8 cases with
      immunohistochemical  expression of perineural cell markers.
AB  - Eight cases of ganglioneuroma were examined for a presence of perineural cell
      differentiation, using the immunohistochemical markers epithelial membrane
      antigen (EMA), claudin-1 and GLUT-1. The mean age of the patients was 42.3 years
      (range 26-68 years), six patients were females and two were males. Five tumors
      were located in the adrenal gland and 3 tumors in the retroperitoneum. Morphology
      of the tumors was typical, i.e., they were composed of neuroid spindle cell
      population and scattered mature appearing ganglion cells. Spindle cells positive
      for perineural cell markers claudin-1 and GLUT-1 were found in all lesions, at
      least focally. EMA+ cells were seen in 2 of 8 tumors. These perineural-type cells
      were often arranged in organoid fashion around the schwannoid bundles or around
      the vessels. Our findings indicate that perineural cell differentiation is
      commonly present in ganglioneuromas.

PMID- 23121032
TI  - [Expression of p57 marker in differential diagnosis of complete and partial mole 
      correlation with DNA analysis].
AB  - Nowadays valid classification of gestational trophoblastic disease, according to
      the World Health Organisation from the year 2003, divides gestational
      trophoblastic disease into three groups - molar pregnancies, non-neoplastic non
      molar changes of trophoblast and tumours of trophoblast. To the molar pregnancies
      belong complete, partial, invasive and metastatic hydatidiform mole. In the
      differential diagnosis it is important to distinguish the complete hydatidiform
      mole from other forms of gestational trophoblastic disease, because there is an
      increased risk of malignant transformation of trophoblast cells in complete
      hydatidiform mole. 10 cases of genetically confirmed diploid complete mole and 10
      cases of genetically confirmed triploid partial mole were included into our
      retrospective study. All cases were examined microscopically in the basic
      haematoxillin and eosin staining and immunohistochemically with the use of
      antibodies against human choriogonadotropin hormone, placental alkaline
      phosfatase and protein p57. Villous cytotrophoblast, stromal villous cells,
      extravillous trophoblast and decidual cells were p57 positive in all cases of
      partial hydatidiform mole. All 10 cases of complete hydatidiform mole were p57
      negative in stromal villous cells and villous cytotrophoblast. P57 protein is a
      marker distinguishing complete hydatidiform moles from partial moles.

PMID- 23121033
TI  - Death due to peripheral vascular  injury following blunt trauma.
AB  - According to the document of death, 34-year-old forester sustained a crush injury
      to his lower extremity and pelvis as was pinned between the wood log and ground.
      During autopsy intramuscular bleeding was observed in the left pelvic region the
      left femoral region femur was detected intact there was no fracture, but there
      was observed a traumatic transection of the common femoral artery and vein, which
      was accompanied with massive bleeding in the surrounding soft tissues and
      muscles. We presented rare case of traumatic transection of the common femoral
      artery and vein in a patient without an femoral fracture caused by blunt trauma.
      KEYWORDS: blunt trauma - peripheral vascular injury - autopsy.

PMID- 23121034
TI  - Sudden death due to a rare brain tumor: an autopsy case.
AB  - Sudden death in persons with intracranial neoplasms is a rare mechanism of death
      detected in the forensic autopsies. 10 years-old girl was brought to a local
      clinic death shortly after analgesic therapy for headache. Autopsy findings
      showed a large, solid cerebellar mass. Histological diagnosis was pilomyxoid
      astrocytoma, low-grade tumor with features alike to pilocytic astrocytomas. In
      this case report we present and discuss rare autopsy case of pilomyxoid
      astrocytoma from medicolegal point of view. KEYWORDS: sudden death - brain -
      pilomyxoid astrocytoma - autopsy.

PMID- 23121035
TI  - Cranial injury caused by penetrating non-missile foreign body: an autopsy case.
AB  - Presented case was 32-year-old male marble worker, who underwent industrial
      accident at workplace. On gross physical examination; on forehead region round
      skin wound in 0.9 cm diameter was detected, radiological examination showed the
      image of metallic object. in the skull cavity. Brain dissection showed obvious
      brain injury, haemorrahge explaining the pattern of injury caused by the metallic
      bodys path, from left frontal lobe to the left cerebellar hemisphere was
      identified. We presented rare case of penetrating injury of the cranial region
      caused by non-missile foreign body. KEYWORDS: cranial injury - non-missile
      foreign body - autopsy.

PMID- 23121036
TI  - Unusual head and neck injury in elevator:  autopsy study.
AB  - Industrial injuries related to auto-load-carrying vehicles were not frequently
      reported in the literature. Presented case was, 31-year-old male furniture
      worker. Deceased was found in awkward position in furniture workshop. Victim was
      observed on his knees in front of the elevator, head and neck lodged within
      openings of the elevator, and head and neck structures compressed-guillotined by
      the lower platform of the elevator were detected. We presented rare case of head
      and neck compression by elevator. Key words:  head - neck - accidents - elevator 
      autopsy.

PMID- 23121037
TI  - Involvement of glucocorticoid receptor on hyperpyrexia  induced by
      methamphetamine administration.
AB  - We have investigated the involvement of glucocorticoid on methamphetamine (MA)
      induced hyperpyrexia using a bio-telemetric system. A significant level of
      hyperpyrexia was observed in MA administered rats. In contrast, increase of body
      temperature was suppressed by adrenalectomy or by the administration of RU-486,
      an antagonist of the glucocorticoid receptor. These data suggest that the
      glucocorticoid receptor may be involved in hyperpyrexia induced by MA. KEYWORDS:
      methamphetamine - hyperpyrexia - glucocorticoid - corticosterone.

PMID- 23121038
TI  - A fatal case due to cough syrup abuse.
AB  - We describe here a fatal abused case of cough syrup, containing chlorpheniramine
      and dihydrocodeine. Postmortem blood concentration of chlorpheniramine was above
      fatal levels, but dihydrocodeine concentration was within a therapeutic ranges,
      and those drug levels in blood were discussed from the viewpoint of forensic
      pharmacokinetics. We concluded that the cause death was due to the
      chlorpheniramine poisoning. KEYWORDS: cough syrup abuse - chlorpheniramine -
      dihydrocodeine.

PMID- 23121039
TI  - Fatal and survived motorcycle accidents: a selected topics for medicolegal
      evaluation.
AB  - Motorcyclists are extremely vulnerable road participants who are exposed to
      severe, often fatal injuries. Relative to four - wheeled vehicles, motorcycle
      pose a greater hazard of death or serious injury to operators and passengers. In
      fatal crashes, the motorcyclist typically collides with moving or stationary
      objects in the riding environment. The most common mechanism of crashes is
      hitting a moving vehicle followed by hitting a stationary object. The mechanism
      of injury resulting in death usually comes from severe blunt force trauma,
      creating internal and external injuries to the motorcyclist, especially
      craniocerebral, spinal, and sometimes with very characteristic injury patterns.
      The paper also identified effects of alcohol, which represent a significant risk
      factor for motorcycle operators. Presented concise review of selected risk
      factors and typical motorcycle-related injuries may be useful for both forensic
      pathologists, clinicians and law enforcement in preventive and repressive steps.
      KEYWORDS: motorcycle fatalities - risk factors - injury patterns - alcohol
      impairment - medicolegal study.

PMID- 23121040
TI  - Effects of alcohol on the brain biomembranes: a review.
AB  - Alcohol consumption is a worldwide spread phenomenon influence of which on a
      human organism may even be fatal. Consequences of alcoholism are not only medical
      but also social and economical. The basic principles of alcohol dependence
      development remain still unclear. Submitted article offers a short review of
      alcohols effects mechanisms and its interaction with neurotransmitters. KEYWORDS:
      alcohol - biomembranes fluidity - GABA - dopamine - serotonine -
      neurotransmitters.

PMID- 23121041
TI  - [Two anniversaries in Czech forensic medicine].
AB  - The authors commemorate the 100th anniversary of the publication of Slaviks
      textbook Forensic Pathology for Medical and Legal Students and the 125th
      anniversary of the 1st Czech forensic autopsy. They introduce professor V. Slavik
      and describe his personal qualities and expertise. The content of the textbook is
      described. The topicality of Slaviks explanations and the tradition of Czech
      forensic pathology are discussed. Key words:  forensic pathology - history of
      Czech forensic pathology - textbooks of forensic pathology.

PMID- 23121042
TI  - Predictors of elective pregnancy termination among women diagnosed with HIV
      during pregnancy in two regions of China, 2004-2010.
AB  - OBJECTIVE:   To document the rates of abortion among women diagnosed with HIV
      during pregnancy in two regions of China, and to investigate the sociodemographic
      factors associated with women's decisions to terminate their pregnancy. DESIGN:  
      Prospective cohort study. SETTING:   Three central Chinese provinces (Hubei,
      Hebei and Shanxi) and Yining, Xinjiang. POPULATION: Women diagnosed with HIV
      during pregnancy, 2004-2010. METHODS:   Of 798 HIV-infected pregnant women
      identified through routine screening of pregnant women via antenatal care between
      2004 and 2010, 499 women made decisions about the outcome of pregnancy. Chi
      squared test was used to describe the characteristics of women who chose to
      terminate their pregnancies. Logistic regression models were used to identify
      potential predictors for pregnancy outcome for one cohort of women in central
      China and a second cohort of women in Yining, Xinjiang. MAIN OUTCOME MEASURES:  
      Pregnancy outcome, trends of elective pregnancy termination. RESULTS:   In the
      central China cohort, 76 of 161 pregnancies (47.2%) were terminated. In Yining,
      the proportion was significantly less, at only 61 of 338 (18.0%). Factors
      associated with pregnancy termination included unmarried marital status, already
      having one or more children and earlier trimester of pregnancy at the time of
      diagnosis. CONCLUSIONS:   The rate of pregnancy termination in these cohorts of
      HIV-infected women appears to be higher than the rate in the general population
      of women in China. More work needs to be carried out to decrease the social
      stigma related to HIV and to convey clear messages about the effectiveness of
      prevention of mother to child transmission to women and their families. The
      significantly lower rate of pregnancy termination in Yining relative to central
      China is probably a result of the cultural and religious reservations towards
      pregnancy termination. Healthcare workers providing services to HIV-infected
      pregnant women need to be sensitive to cultural factors influencing women's
      decisions with regard to pregnancy termination.

PMID- 23121043
TI  - TV viewing and obesity among Norwegian children: the importance of parental
      education.
AB  - AIM: To analyse the effect of lifestyle factors on the prevalence of overweight
      and obesity in 6-15-year-old Norwegian children. METHODS: Questionnaire data on
      lifestyle factors (sedentary behaviour, activity and eating habits) and
      prevalence numbers of overweight and obesity based on measured height and weight
      were analysed using multinomial logistic regression in a sample of 2281 children
      included in the Bergen Growth Study. RESULTS: More screen time increased the risk
      of overweight (odds ratio (OR): 1.25; p = 0.02) and obesity (OR: 1.12; p = 0.02)
      as did the presence of a TV in the child's bedroom (OR: 1.26 (overweight), OR:
      1.81 (obese); p = 0.04). The obese children reported less sugar intake than the
      not overweight children (OR: 0.58; p = 0.01). Higher parental education was
      associated with less screen time (p = 0.02), lower frequency of TV in the child's
      bedroom (p = 0.001), more sports (p = 0.005), as well as eating more fruit and
      vegetables, less sweets, soft drinks and fast food, and more regular meals (for
      all, p < 0.03). CONCLUSION: Indicators of sedentary lifestyle, such as screen
      time and the presence of a TV in the child's bedroom, were associated with
      overweight and obesity in Norwegian schoolchildren. Higher parental education was
      generally associated with less obesogenic lifestyle.

PMID- 23121044
TI  - Plant memory: a tentative model.
AB  - All memory functions have molecular bases, namely in signal reception and
      transduction, and in storage and recall of information. Thus, at all levels of
      organisation living organisms have some kind of memory. In plants one may
      distinguish two types. There are linear pathways from reception of signals and
      propagation of effectors to a type of memory that may be described by terms such
      as learning, habituation or priming. There is a storage and recall memory based
      on a complex network of elements with a high degree of integration and feedback.
      The most important elements envisaged are calcium waves, epigenetic modifications
      of DNA and histones, and regulation of timing via a biological clock. Experiments
      are described that document the occurrence of the two sorts of memory and which
      show how they can be distinguished. A schematic model of plant memory is derived
      as emergent from integration of the various modules. Possessing the two forms of
      memory supports the fitness of plants in response to environmental stimuli and
      stress.

PMID- 23121045
TI  - Australian university students' attitudes towards the use of prescription
      stimulants as cognitive enhancers: perceived patterns of use, efficacy and
      safety.
AB  - INTRODUCTION AND AIMS: Recent, high profile articles in leading science journals
      have claimed that the enhancement use of prescription stimulants is a common
      practice among students worldwide. This study provides empirical data on
      Australian university students' perceptions of: (i) the prevalence of
      prescription stimulant use by their peers for cognitive enhancement; (ii)
      motivations for such use; (iii) efficacy; and (iv) its safety. DESIGN AND
      METHODS: Participants were 19 Australian university students with an average age
      of 24 who were recruited through emails lists, notice board posters and snowball
      sampling. Semi-structured interviews were conducted during 2010 and 2011,
      recordings transcribed and responses coded using thematic analysis. RESULTS:
      Participants typically did not believe the use of stimulants for cognitive
      enhancement was common in Australia. Perceived motivations for use included: (i)
      'getting ahead' to perform at high levels; (ii) 'keeping up' as a method of
      coping; and (iii) 'going out' so that an active social life could be maintained
      in the face of study demands. Australian students were generally sceptical about
      the potential benefits of stimulants for cognitive enhancement and they
      identified psychological dependence as a potential negative consequence.
      DISCUSSION AND CONCLUSIONS: This study is an important first step in
      understanding the use of stimulants for cognitive enhancement in Australia, amid
      calls for more widespread use of cognitive enhancing drugs. It is important to
      conduct further studies of the extent of cognitive enhancement in Australia if we
      are to develop appropriate policy responses.

PMID- 23121046
TI  - Predictors of high defibrillation threshold in the modern era.
AB  - INTRODUCTION: High defibrillation threshold (DFT) is a clinical problem in 1-8%
      of implantable cardioverter-defibrillator implants. Some clinicians and
      investigators question whether the benefits of routine DFT testing outweigh the
      risks. Identification of the predictors of elevated DFT may allow selective
      application of DFT testing. However, the clinical characteristics of patients
      with high DFT in the modern era have not been well-defined. METHODS: All patients
      who underwent DFT testing in our institution during an 8-year period were
      reviewed for this retrospective study. High DFT was defined as less than a 10-J
      safety margin on initial testing. For each case, the two cases preceding and two
      cases following by the same implanter were selected as controls. RESULTS: Of the
      2,138 patients who underwent DFT testing, 48 (2.2%) met criteria for high DFT.
      Compared to 192 control patients, patients with high DFT were more likely to be
      younger (P = 0.004), have nonischemic cardiomyopathy (P = 0.036), have a longer
      QRS interval (P = 0.026), and have a left ventricular ejection fraction (LVEF) <=
      0.25 (P = 0.013). On multivariate analysis, only younger age (P = 0.016) and LVEF
      <= 0.25 (P = 0.010) remained statistically significant predictors of elevated
      DFT. CONCLUSIONS: High DFT was identified in 2.2% of ICD implants in our
      institution in recent years. Although younger age and depressed LVEF predicts
      this problem, elevated DFT occurred in patients of all ages and ejection
      fractions. Elimination of routine DFT testing appears to be premature given the
      prevalence and unpredictability of elevated DFT.

PMID- 23121047
TI  - Differential distribution of lymphatic clearance between upper and lower regions
      of the lung.
AB  - BACKGROUND AND OBJECTIVE: Many lung diseases arise as the consequence of
      inhalational injury. When pathogenic materials are inhaled, it is possible that
      their clearance routes become the main focus of injury in the lung. Lymphatic
      clearance is important in the removal from the lung of small inhaled particles.
      The leak of toxic agents from the lymphatic flow potentially explains the
      topographic distribution of diffuse lung diseases triggered by inhaled materials,
      for example asbestosis. The aim of this study was to evaluate the differences in
      lymphatic distribution across various craniocaudal levels of the lung by using
      carbon dust deposition (CDD) as a tracing marker. METHODS: We evaluated 61 HE
      stained slides of the normal lung area from 61 lobectomy specimens. The intensity
      of CDD was scored into five degrees (0-4) in bronchiolovascular (BV) areas and
      subpleural/septal (SP) areas per slide. The distribution was highlighted by
      subtraction scores of SP areas from those of bronchiolovascular areas. RESULTS:
      The subtraction scores of the upper lung area were significantly greater than
      those in the lower area, whereas there was no significant difference in scores by
      pulmonary lobes. CONCLUSIONS: Our results indicated that the main lymphatic
      clearance routes vary according to the craniocaudal levels, and are predominant
      in BV areas of the upper areas and in SP areas of the lower areas of the lung.
      This may explain the histological variations in anatomical distribution observed
      in the biopsy specimens of some diffuse lung diseases.

PMID- 23121048
TI  - Quality of life in cervical cancer patients treated with radiation therapy.
AB  - AIMS AND OBJECTIVES: To evaluate the quality of life in hospitalised patients
      with cervical cancer treated by radiation therapy. BACKGROUND: Aside from
      clinical variables, the quality of life should be considered in the planning and
      monitoring of the therapeutic process in patients with cancer. Although it is
      widely known that this parameter can have a considerable impact on the
      therapeutic outcome, it is not routinely screened in oncological patients.
      DESIGN: Survey. METHODS: The study was performed in six cancer centres in Poland
      between June 2004-December 2005, and included 205 women hospitalised for any
      stage of cervical cancer. The EORTC QLQ-C30 questionnaire (v.3) was used to
      evaluate the patients' quality of life. The survey was conducted three times: (1)
      stage 1 - before treatment, on admission, (2) stage 2 - after treatment, at
      discharge, and (3) stage 3 - five to six months after treatment. RESULTS:
      Physical functioning was assessed the worst before the radiation treatment and
      increased gradually throughout further stages; all interstage differences proved
      to be significant. In contrast, emotional functioning was scored the highest
      before the initiation of the treatment and was the lowest at stage 2, a
      difference that proved to be significant. Role functioning was highest
      immediately after the treatment and the lowest prior to the treatment.
      Differences between stages proved to be significant. Financial problems increased
      their negative impact on the quality of patients' lives significantly throughout
      consecutive stages of this study. Age and cancer stage did not significantly
      influence the way participants perceived their global health, physical,
      cognitive, emotional and social functioning, nor their financial difficulties.
      Overall, the quality of life was evaluated as highest immediately after the end
      of radiotherapy. CONCLUSION: Although this study revealed that patients with
      cervical cancer subjected to radiotherapy are satisfied with their global quality
      of life, attention should be paid to certain dimensions of the latter (i.e.
      emotional functioning and role functioning) during post-treatment period.
      RELEVANCE TO CLINICAL PRACTICE: The ability to performing everyday activities
      independently is perceived as the most important during all stages of the
      cervical cancer treatment, and therefore, appropriate support in this matter is
      necessary on the part of the nursing personnel.

PMID- 23121049
TI  - Functional GPR37 trafficking protects against toxicity induced by 6-OHDA, MPP+ or
      rotenone in a catecholaminergic cell line.
AB  - G protein-coupled receptor 37 (GPR37) is suggested to be implicated in the
      pathogenesis of Parkinson's disease and is accumulating in Lewy bodies within
      afflicted brain regions. Over-expressed GPR37 is prone to misfolding and
      aggregation, causing cell death via endoplasmic reticulum stress. Although the
      cytotoxicity of misfolded GPR37 is well established, effects of the functional
      receptor on cell viability are still unknown. An N2a cell line stably expressing
      green fluorescent protein (GFP)-tagged human GPR37 was created to study its
      trafficking and effects on cell viability upon challenge with the toxins 1-methyl
      4-phenylpyridinium (MPP+), rotenone and 6-hydroxydopamine (6-OHDA). Neuronal-like
      differentiation into a tyrosine hydroxylase expressing phenotype, using dibutyryl
      cAMP, induced trafficking of GPR37 to the plasma membrane. 3-(4,5-Dimethylthiazol
      2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability and lactate
      dehydrogenase (LDH) cell death assays revealed that GPR37 was protective against
      all three toxins in differentiated cells. In undifferentiated cells, the majority
      of GPR37 was cytoplasmic and the protective effects were more variable: GPR37
      expression protected against rotenone and MPP+ but not against 6-OHDA in MTT
      assays, while it protected against 6-OHDA but not against MPP+ or rotenone in
      lactate dehydrogenase (LDH) assays. These results suggest that GPR37 functionally
      trafficked to the plasma membrane protects against toxicity.

PMID- 23121050
TI  - The authors' reply: DHEA and quality of life.

PMID- 23121051
TI  - Indoor dust and air concentrations of endotoxin in urban and rural environments.
AB  - SIGNIFICANCE AND IMPACT OF THE STUDY: Rural dairy farming is associated with high
      exposure to indoor endotoxins as compared to rural nonfarming houses and urban
      houses. The time spent on the mattress (7 h for an adult) and of the proximity of
      the contaminated source should be taken into account with the other causes of
      exposure. Studies in European children from a farming background have shown that
      these children have a reduced risk of asthma and atopic sensitization compared to
      their urban counterparts. It has been suggested that this might be due to
      exposure to high levels of endotoxin in the farming environment. The aim of this
      study was to compare indoor endotoxin concentrations in air and dust samples from
      randomly selected urban and rural dwellings. In the rural area, endotoxins were
      analysed in farmhouses and nonfarmhouses as well as housing characteristics,
      lifestyle factors and agricultural practices likely to influence air and dust
      endotoxin levels. Endotoxin levels were significantly higher in floor (6600 +/-
      6100 vs 3600 +/- 5600 and 3800 +/- 17,000 ng g-1; P < 0.001) and mattress dust
      (2900 +/- 4100 vs 1100 +/- 2400 and 800 +/- 2600 ng g-1; P < 0.001) from
      farmhouses compared to other rural and urban homes. However, no difference was
      observed between endotoxin concentrations in the air of urban and rural houses,
      and airborne endotoxin levels did not correlate to dust levels. Lack of
      ventilation and direct entry into the house were correlated with an increase in
      dust endotoxin levels. These results confirm that dairy farming is associated
      with high exposure to endotoxins in indoor dust samples. No difference was
      observed between indoor airborne concentrations between urban and rural houses.
      These results suggest that measuring endotoxin in dust is the most relevant
      method to assess endotoxin exposure.

PMID- 23121052
TI  - Pathogenesis of the viral hemorrhagic fevers.
AB  - Four families of enveloped RNA viruses, filoviruses, flaviviruses, arenaviruses,
      and bunyaviruses, cause hemorrhagic fevers. These viruses are maintained in
      specific natural cycles involving nonhuman primates, bats, rodents, domestic
      ruminants, humans, mosquitoes, and ticks. Vascular instability varies from mild
      to fatal shock, and hemorrhage ranges from none to life threatening. The
      pathogenic mechanisms are extremely diverse and include deficiency of hepatic
      synthesis of coagulation factors owing to hepatocellular necrosis, cytokine
      storm, increased permeability by vascular endothelial growth factor, complement
      activation, and disseminated intravascular coagulation in one or more hemorrhagic
      fevers. The severity of disease caused by these agents varies tremendously; there
      are extremely high fatality rates in Ebola and Marburg hemorrhagic fevers, and
      asymptomatic infection predominates in yellow fever and dengue viral infections.
      Although ineffective immunity and high viral loads are characteristic of several
      viral hemorrhagic fevers, severe plasma leakage occurs at the time of viral
      clearance and defervescence in dengue hemorrhagic fever.

PMID- 23121053
TI  - Skeletal muscle degenerative diseases and strategies for therapeutic muscle
      repair.
AB  - Skeletal muscle is a highly specialized, postmitotic tissue that must withstand
      chronic mechanical and physiological stress throughout life to maintain proper
      contractile function. Muscle damage or disease leads to progressive weakness and
      disability, and manifests in more than 100 different human disorders. Current
      therapies to treat muscle degenerative diseases are limited mostly to the
      amelioration of symptoms, although promising new therapeutic directions are
      emerging. In this review, we discuss the pathological basis for the most common
      muscle degenerative diseases and highlight new and encouraging experimental and
      clinical opportunities to prevent or reverse these afflictions.

PMID- 23121054
TI  - Diagnostic applications of high-throughput DNA sequencing.
AB  - Advances in DNA sequencing technology have allowed comprehensive investigation of
      the genetics of human beings and human diseases. Insights from sequencing the
      genomes, exomes, or transcriptomes of healthy and diseased cells in patients are
      already enabling improved diagnostic classification, prognostication, and therapy
      selection for many diseases. Understanding the data obtained using new high
      throughput DNA sequencing methods, choices made in sequencing strategies, and
      common challenges in data analysis and genotype-phenotype correlation is
      essential if pathologists, geneticists, and clinicians are to interpret the
      growing scientific literature in this area. This review highlights some of the
      major results and discoveries stemming from high-throughput DNA sequencing
      research in our understanding of Mendelian genetic disorders, hematologic cancer
      biology, infectious diseases, the immune system, transplant biology, and prenatal
      diagnostics. Transition of new DNA sequencing methodologies to the clinical
      laboratory is under way and is likely to have a major impact on all areas of
      medicine.

PMID- 23121056
TI  - Radioactive iodine: a slice of history.

PMID- 23121055
TI  - Pathological and molecular advances in pediatric low-grade astrocytoma.
AB  - Pediatric low-grade astrocytomas are the most common brain tumors in children.
      They can have similar microscopic and clinical features, making accurate
      diagnosis difficult. For patients whose tumors are in locations that do not
      permit full resection, or those with an intrinsically aggressive biology, more
      effective therapies are required. Until recently, little was known about the
      molecular changes that drive the initiation and growth of pilocytic and other low
      grade astrocytomas beyond the association of a minority of cases, primarily in
      the optic nerve, with neurofibromatosis type 1. Over the past several years, a
      wide range of studies have implicated the BRAF oncogene and other members of this
      signaling cascade in the pathobiology of pediatric low-grade astrocytoma. In this
      review, we attempt to summarize this rapidly developing field and discuss the
      potential for translating our growing molecular knowledge into improved
      diagnostic and prognostic biomarkers and new targeted therapies.

PMID- 23121057
TI  - [Acute myocardial infarction in young patients--severe failures in the system of
      acute and secondary care].
AB  - INTRODUCTION: The incidence of cardiovascular (CV) diseases and acute myocardial
      infarction (AMI) in Czech Republic is de-clining. In spite of this in a
      proportion of patients AMI occurs in young age. The aim of our project was to
      assess the character of risk factors, precipitating diseases and the quality of
      care in young AMI survivors. METHODS: We included 132 patients (97 men and 35
      women) in whom AIM with ST elevations occurred before age of 45 years in men and
      age of 50 years in women. Several results were compared to a control group
      composed of 84 healthy volunteers of comparable age. We assessed the course of
      the disease, extent of coronary involvement, subsequent therapy and control of
      risk factors after 3 years from the index event. RESULTS: Smoking represented the
      main risk factor - 85% patents were active smokers at the time of AMI and 9% were
      former smokers, 64% patients had a positive family history of CV disease. We
      found a higher prevalence of dyslipidemia history in men. In spite of high rate
      of statin use, laboratory examination during follow-up revealed higher
      triglyceride values and low levels of HDL-cholesterol in both genders. All
      together 23% of patients had a history of provoking underlying disease or
      precipitating factors (inflammatory diseases, malignancies, combined
      thrombophilias, drug abuse). In total 95% of patients underwent coronary
      angiography during the acute phase of AMI, the median time from pain onset to
      intervention was 9 hours. Most patients had single vessel disease, 14% had even
      coronary angiogram without clinically significant stenosis. The subsequent care
      was satisfactory concerning the rate of drug prescriptions. However, target lipid
      values were not reached in 78% patients and blood pressure targets in 37%.
      CONCLUSIONS: In patients who suffered AMI in young age, risk factors are
      dominated by smoking and positive family history of CV diseases. One fifth of
      patients suffer from other underlying disease (inflammatory disease,
      malignancies, combined thrombophilia) or have another precipitating factor
      (febrile disease, drug abuse). The acute care seems unsatisfactory due to late
      arrival of most patients to catheterization laboratories (underestimation of the
      disease, incorrect initial diagnosis). Subsequent therapy is well composed but
      lacks in intensity.

PMID- 23121058
TI  - [Is there a relationship between inflammatory markers, oxidative stress and
      postoperative atrial fibrillation?].
AB  - INTRODUCTION: Atrial fibrillation (AF) is one of the most common complications
      following heart surgery. The aim of this work was to verify the relationship
      between inflammatory markers, oxidative stress and postoperative arrhythmia.
      METHODS: 45 patients with ischemic heart disease (12 women and 33 men, mean age
      62.3 +/- 9.4 years) underwent surgical myocardial revascularization. The
      extracorporeal circulation (ECC) was used in 30 patients, without ECC was 15
      patients. During the first 3 postoperative days was determining the incidence and
      duration of the AF, laboratory markers of inflammation (CRP, leukocytes,
      TNFalpha), malondialdehyde (MDA). RESULTS: Demographic data and associated
      disease were in this patients similar. The incidence of AF we documented in 30
      patients (66.7%). In patients with postoperative AF were significantly higher
      levels of inflammatory markers (leukocytes 13.6 +/- 3.6 vs 11.3 +/- 3.6; 14.7 +/-
      3.9 vs 12.5 +/- 2.9; 13.7 +/- 4.1 vs 11.4 +/- 13.7; p 0.05; CRP 138.1 +/- 41.1 vs
      69.9 +/- 25.8; p 0.001; TNFalpha 11.3 +/- 14.3 vs 8.7 +/- 3.6; 12.1 +/- 14.5 vs
      8.7 +/- 3.1; p 0.05) compared with patients who were free from AF. Values of MDA
      were not significantly different. CONCLUSION: Patients with post-operative atrial
      fibrillation were higher levels of inflammatory markers compared with patients
      with sinus rhythm but no significant differences in the levels of oxidative
      stress.

PMID- 23121059
TI  - [Sarcoidosis--diagnostics, prognosis and therapy. A retrospective analysis].
AB  - Sarcoidosis is systematic granulomatous disease of unknown etiology which can
      affect any organ. Sarcoidosis belongs to diseases called interstitial lung
      diseases. Our study is a retrospective analysis of 169 patients (100 females and
      69 males), whom we diagnosed sarcoidosis at our pulmonary department in years
      2005-2010. Aim of the analysis was to find out prognostic factors and to describe
      the course of disease. Median age of sarcoidosis patients was 48 years (20-79).
      Females : males ratio was 1.5 : 1. Non smoker : smoker (or former smoker) ratio
      was 2.2 : 1. Familial occurrence was observed in 4 patients (2.4%). At diagnosis,
      stage 0 was present in 6 (3.5%) patients, stage I in 58 (34%) patients, stage II
      in 84 (49.5%) patients, stage III in 18 (11%) patients, and stage IV in 3 (2%)
      patients. Diagnosis was confirmed by histology in 111 patients. In 76 patients
      there was extrapulmonary sarcoidosis. The coincidence of sarcoidosis with
      autoimmune diseases was observed in 10 patients; 6 patients developed
      trombembolic disease. One patient suffered from sarcoidosis with cystic fibrosis.
      Spontaneous resolution was seen in 65 (38.5%) patients; 37 (64%) stage I
      patients, 26 (31%) stage II patients, and 2 (11%) stage III patients. One hundred
      one patients (60%) received corticosteroids. Adverse events of corticosteroid
      therapy were observed in 28 (26%) patients. In sarcoidosis patients with
      spontaneous resolution, no relapse of disease was observed. On the other hand,
      eleven (11%) patients treated with glucocorticosteroids relapsed. Median time to
      sarcoidosis relapse was 6 months (2-34). The age under 40 years, the X-ray stage
      I or II, the high CD4/CD8 ratio in bronchoalveolar fluid, pulmonary involvement,
      and therapy need for a period shorter than 2 years were assessed as a significant
      good prognostic factors. Observed lethality of our patient cohort was 1.2% (2
      patients; both deaths related to sarcoidosis).

PMID- 23121060
TI  - [Vitamin C and its physiological role with respect to the components of the
      immune system].
AB  - Vitamin C is a water soluble micronutrient commonly found in our diet which
      orchestrates the function of both innate and adaptive immune system, influencing
      both cellular and humoral immune responses. Vitamin C inhibits excessive
      activation of the immune system to prevent tissue damage, but also supports
      antibacterial activity, stimulates NK cells and differentiation of Th0 subset
      into Th1 characterized by interferon gamma production. In addition, vitamin C
      interferes with the synthesis of proinflammatory cytokines, or with the
      expression of adhesive molecules. Moreover, vitamin C as an antioxidat protects
      the immune cells against intracellular ROS (reactive oxygen species) formed in
      the inflammatory response. Vitamin C as an enzymatic cofactor is extremely
      important in maintaining tissue integrity, and plays a crucial role in formation
      of skin, epithelial and endothelial barriers.

PMID- 23121061
TI  - [Hypoglycaemia--a phenomenon over which modern diabetology manages to prevail].
AB  - Hypoglycaemia is considered to be the most significant complication when treating
      diabetes. The most important is its association with cardiovascular risk.
      Rigorous self-monitoring, lifestyle changes and the use of insulin analogues
      reduce the risk significantly in type 1 diabetes patients. Combined insulin and
      incretin therapy appears to be useful. Individualized therapy and incretin
      treatment in particular represent considerable risk reduction in type 2 diabetes
      patients. It is crucial to change therapy in a patient who underwent
      hypoglycaemia. Modern antidiabetic therapy helps to surmount the risk of
      hypoglacaemia and it is possible at any stage of type 2 diabetes treatment to
      select therapy with lover risk of hypoglacaemia: incretin therapy is the most
      suitable following metformin treatment failure, incretin analogues are the most
      suitable when oral antidiabetic agents fail, and insulin analogues are the most
      appropriate when insulin therapy is to be initiated. Key words:  cardiovascular
      risk - insulin therapy - incretin therapy - oral antidiabetic medication -
      insulin analogues.

PMID- 23121062
TI  - [AII antagonists (candesartan and irbesartan) in the treatment of cardiovascular
      diseases].
AB  - Treatment of hypertension with angiotensin II receptor antagonists (AIIA) was
      first limited to diabetics and patients with microalbuminuria. So far, results of
      several large clinical trials with AIIAs were published, confirming significant
      renoprotective effect of these agents compared to placebo (RENAAL and IRMA),
      amlodipin (MARVAL and IDNT) and a combination of ACEI and AIIA (CALM). In 2002,
      results of 2 large comparator studies in hypertension were published: LIFE -
      Losartan Intervention For Endpoints and SCOPE - the Study on COgnition and
      Prognosis in Elderly hypertensives. In 2003, a series of the CHARM studies
      involving patients with heart failure were published and, from than, AIIA have
      been used as an alternative to ACEI or in a combination with ACEI. MOSES study -
      Morbidity and mortality after stroke, eprosartan compared with nitrendipine for
      secondary prevention - results were published in 2005 and ONTARGET study,
      focusing on secondary prevention of ischemic heart disease, was published in
      2008. The CORD study - Comparison of recommended doses - and the ACTIVE I study
      (AF Clopidogrel Trial with Irbesartan for prevention of Vascular Events) were
      published in 2009. Candesartan was used in the CALM, SCOPE, RESOLVED and CHARM
      studies, irbesartan in the IRMA, IDNT and ACTIVE I.

PMID- 23121063
TI  - [Febrile pancytopenia and hepatosplenomegaly as leading symptoms of visceral
      leishmaniasis].
AB  - The authors present a case report of a patient with febrile pancytopenia,
      hepatosplenomegaly and weight loss as main symptoms of visceral leishmaniasis.
      Standard treatment regimen with amphothericin B led to relapse of the disease
      after several weeks. The definitive cure of the disease was achieved with
      cytostatic miltefosin (Impavido(c)), which is not registered in the Czech
      Republic. The aim of this article is to point out this imported protozoan
      infection and its basic clinical and laboratory features.

PMID- 23121064
TI  - [High suspicion of heart disease gained from taking the case history must not
      controvert negative results of some medical examination--experience of an
      outpatient internist].
AB  - We report the case of a patient having atypical chest pain and difficult to
      breathe. The cardiac gated SPECT had insignificant result in compare with high
      positive results of coronary artery calcium score and coronarography.

PMID- 23121065
TI  - [Dabigatran etexilate in clinical practice for prevention of thromboembolic
      events in patients with atrial fibrillation].
AB  - Dabigatrane is the first new generation antiacoagulant that at a dose of 150 mg
      twice daily was, in the RE-LY study, more effective in cerebrovascular event and
      systemic embolisation prevention than well-controlled warfarin and had comparable
      or better safety profile than well-controlled warfarin. The 110 mg twice daily
      dose showed comparable efficacy and superior safety against warfarin. Crucial and
      unique among modern anticoagulants is its ability to significantly reduce
      ischemic as well as hemorrhagic CVEs at a dose of 150 mg twice daily. In
      addition, dabigatran significantly facilitates management of patients with atrial
      fibrillation as it does not require laboratory monitoring, has predictable
      pharmacokinetics, simple dosing regimen that does not require complicated dose
      adjustments, and does not interact with food. However, it is important to
      remember that it is an anticoagulant. Care should, therefore, be exercised when
      the treatment is indicated, renal function has to be known and it needs to be
      kept in mind that, as with any anticoagulant, the treatment may be associated
      with bleeding. However, when indication criteria are observed, the above listed
      advantages considered and careful patient monitoring put in place, the bleeding
      will be, compared to standard warfarin treatment, minimized. Key words: 
      dabigatran - atrial fibrillation - tromboembolism.

PMID- 23121066
TI  - [Effect of ivabradin on heart rate, left ventricular function a NT-proBNP
      concentration in patients with systolic chronic heart failure--case reports].
AB  - Ivabradin is indicated in patients with compensated chronic heart failure and
      sinus rhythm with resting heart rate 75 beats per minute despite maximal
      tolerated beta-blocker dose. Three case reports show favourable effect of
      ivabradin therapy on heart rate, reverse cardiac remodeling and B-type
      natriuretic peptide concentration in patients with systolic heart failure.

PMID- 23121067
TI  - [Diagnosis and treatment of arterial hypertension. 2012 Guidelines of the Czech
      Hypertension Society].

PMID- 23121068
TI  - Functional preservation of deep brain stimulation electrodes after brain shift
      induced by traumatic subdural haematoma - case report.
AB  - A Parkinson's disease patient with deep brain stimulation (DBS) implantation
      experienced an acute subdural haematoma (SDH) after a fall. The DBS electrodes
      and brain parenchyma were shifted. Fortunately, the patient recovered after
      craniectomy and removal of SDH, and the DBS was re-activated with the same
      parameters. Patients with DBS implants who suffer a traumatic brain injury do not
      necessarily incur permanent implant failure; there is every chance that the DBS
      may continue to work as reported here.

PMID- 23121069
TI  - Acute myeloid leukemia with monosomy 20 and diabetes insipidus: a possible novel
      association.

PMID- 23121070
TI  - Photochemistry of mycolactone A/B, the causative toxin of Buruli ulcer.
AB  - Photochemistry of mycolactone A/B and related unsaturated fatty acid esters is
      reported. On exposure to visible light, mycolactone A/B gave a mixture of four
      photomycolactones. Pentaenoates and tetraenoates, representing the unsaturated
      fatty acid portion of mycolactone A/B, were found to show the reactivity profile
      parallel with that of mycolactone A/B. The structure of the four
      photomycolactones was elucidated via (1) structure determination of the four
      photoproducts in the tetraenoate series; (2) their transformation to the
      photoproducts in the pentaenoate and then mycolactone series. Triplet quenchers
      did not affect the photochemical transformation, thereby indicating an event at
      the singlet state. A concerted, photochemically allowed [4pis + 2pia]
      cycloaddition was suggested to account for the observed result. This study
      provided the structurally defined and homogeneous material, which allowed
      demonstration that photomycolactones exhibit significantly reduced cytotoxicity,
      compared with mycolactone A/B.

PMID- 23121071
TI  - Coconfinement of fluorescent proteins: spatially enforced communication of GFP
      and mCherry encapsulated within the P22 capsid.
AB  - The precise architectures of viruses and virus-like particles are proving to be
      highly advantageous in synthetic materials applications. Not only can these
      nanocontainers be harnessed as active materials, but they can be exploited for
      examining the effects of in vivo "cell-like" crowding and confinement on the
      properties of the encapsulated cargo. Here we report the first example of
      intermolecular communication between two proteins coencapsulated within the
      capsid architecture of the bacteriophage P22. Using a genetically engineered
      three-protein fusion between the P22 scaffold protein, and the FRET pair, GFP,
      and a red fluorescent protein (mCherry), we were able to direct the encapsulation
      of the genetic fusion when coexpressed with P22 coat protein. These self
      assembled P22 capsids are densely packaged, occupying more than 24% of the
      available volume, and the molecular design assures a 1:1 ratio of the interacting
      proteins. To probe the effect of crowding and confinement on the FRET
      communication in this nanoenvironment, we spaced the donor-acceptor pair with
      variable length flexible linkers and examined the effect on FRET inside the
      capsid compared to the same tethered FRET pairs free in solution. The P22 system
      is unique in that the capsid morphology can be altered, without losing the
      encapsulated cargo, resulting in a doubling of the capsid volume. Thus, we have
      additionally examined the encapsulated fusions at two different internal
      concentrations. Our results indicate that FRET is sensitive to the expansion of
      the capsid and encapsulation enforces significant intermolecular communication,
      increasing FRET by 5-fold. This P22 coencapsulation system is a promising
      platform for studying crowding, enforced proximity, and confinement effects on
      communication between active proteins.

PMID- 23121072
TI  - Alcohol industry sponsorship and alcohol-related harms in Australian university
      sportspeople/athletes.
AB  - INTRODUCTION AND AIMS: Although there is evidence that alcohol sponsorship in
      sport is related to greater drinking, there is no empirical research on whether
      alcohol sponsorship is associated with alcohol-related harms. We examined whether
      there is an association between receipt of alcohol industry sponsorship, and
      attendance at alcohol sponsor's drinking establishments (e.g. bars), and alcohol
      related aggression and antisocial behaviour in university students who play
      sport. DESIGN AND METHODS: University sportspeople (n = 652) completed surveys
      (response rate >80%) assessing receipt of alcohol industry sponsorship,
      attendance at sponsor's establishments and confounders [i.e. age, gender, sport
      type, location and alcohol consumption measured by Alcohol Use Disorders
      Identification Test--alcohol consumption (AUDIT-C) scores]. Participants also
      completed measures assessing displays and receipt of aggressive and antisocial
      behaviours (e.g. assaults, unwanted sexual advance, vandalism). RESULTS: Logistic
      regression models including confounders and reported attendance at alcohol
      sponsor's establishments showed that sportspeople receiving alcohol industry
      sponsorship were more likely to have been the victim of aggression (adjusted odds
      ratio 2.62, 95% confidence interval 1.22-5.64). Attending an alcohol sponsor's
      establishment was not associated with higher rates of other aggressive or
      antisocial behaviour. However, significant associations where found between AUDIT
      C scores and having displayed and received aggression, and having damaged or had
      property damaged. Male sportspeople were more likely to have displayed and
      received aggressive and antisocial behaviour. DISCUSSION AND CONCLUSIONS: Higher
      AUDIT-C scores, gender and receipt of alcohol industry sponsorship were
      associated with alcohol-related aggression/antisocial behaviours in university
      sportspeople. Sport administrators should consider action to reduce the harms
      associated with excessive alcohol consumption and alcohol industry sponsorship in
      sport.

PMID- 23121073
TI  - Testing the pediatric cardiac quality of life inventory in the United kingdom.
AB  - AIM: To establish the validity and reliability of the Pediatric Cardiac Quality
      of Life Inventory (PCQLI) for children with heart disease in the United Kingdom.
      METHODS: Three paediatric cardiac centres recruited patients aged 8-18 years with
      heart disease. Patient-parent pairs completed a disease-specific paediatric
      cardiac quality of life measure (PCQLI), a generic quality of life measure
      (PedsQL4.0) and behaviour and self-perception questionnaires. Validity was
      assessed by correlation of PCQLI scores with heart disease severity, medical care
      utilization, and PedsQL, behaviour and self-perception scores, and by correlation
      of patient and parent PCQLI scores. Reliability was evaluated by administering
      the PCQLI at two time points. RESULTS: The study was completed by 771 patient
      parent pairs. Validity was confirmed by the association of lower total PCQLI
      scores with more complex heart disease and a greater number of hospitalizations
      and cardiac surgeries (all p < 0.001); moderate to good correlations between
      patient and parent scores (0.50-0.68); and fair to good correlations between
      scores for the PCQLI and PedsQL4.0 (0.67-0.77), self-perception (0.42-0.49) and
      behaviour measures (0.18-0.62). Test-retest reliability correlations were high
      (0.72-0.90). CONCLUSION: The PCQLI is a reliable and valid disease-specific
      quality-of-life measure for children with heart disease in the United Kingdom.

PMID- 23121074
TI  - The effect of a counselling intervention on weight changes during and after
      pregnancy: a randomised trial.
AB  - OBJECTIVES: To evaluate the effects of a counselling intervention on excessive
      weight gain during pregnancy and postpartum weight retention. DESIGN: The New
      Life(style) study was a randomised trial with a control group (n = 113) and an
      intervention group (n = 106). SETTING: Midwife practices in the Netherlands.
      POPULATION: Women with a healthy pregnancy, expecting their first baby. METHODS:
      The intervention consisted of four face-to-face counselling sessions about
      weight, physical activity and diet during pregnancy, and one session by telephone
      after delivery. MAIN OUTCOME MEASURES: Weight was objectively assessed at 15, 25
      and 35 weeks of gestation, and again at 8, 26 and 52 weeks postpartum. In
      regression models, the intervention effect on gestational weight gain and
      postpartum weight retention was assessed. RESULTS: Women gained on average 11.3
      kg (SD 3.7 kg) from early to late pregnancy. Women were 1.0 kg (SD 5.3 kg)
      lighter at 52 weeks postpartum compared with early pregnancy. The intervention
      had no effect on gestational weight gain (B = -0.05; 95% CI -1.10 to 1.00) or
      postpartum weight (B = 0.94; 95% CI -2.41 to 0.53) in the total study group. In a
      subgroup of overweight and obese women (n = 47), a favourable trend on all
      outcomes was observed, but none of the differences were statistically
      significant. CONCLUSION: The lifestyle counselling intervention evaluated in this
      study did not have an effect on excessive weight gain or postpartum weight
      retention. Our findings for overweight and obese women need to be confirmed in a
      larger, well-designed randomised trial.

PMID- 23121075
TI  - P2-substituted N-acylprolylpyrrolidine inhibitors of prolyl oligopeptidase:
      biochemical evaluation, binding mode determination, and assessment in a cellular
      model of synucleinopathy.
AB  - We have investigated the effect of regiospecifically introducing substituents in
      the P2 part of the typical dipeptide derived basic structure of PREP inhibitors.
      This hitherto unexplored modification type can be used to improve target
      affinity, selectivity, and physicochemical parameters in drug discovery programs
      focusing on PREP inhibitors. Biochemical evaluation of the produced inhibitors
      identified several substituent types that significantly increase target affinity,
      thereby reducing the need for an electrophilic "warhead" functionality.
      Pronounced PREP specificity within the group of Clan SC proteases was generally
      observed. Omission of the P1 electrophilic function did not affect the overall
      binding mode of three representative compounds, as studied by X-ray
      crystallography, while the P2 substituents were demonstrated to be accommodated
      in a cavity of PREP that, to date, has not been probed by inhibitors. Finally, we
      report on results of selected inhibitors in a SH-SY5Y cellular model of
      synucleinopathy and demonstrate a significant antiaggregation effect on alpha
      synuclein.

PMID- 23121076
TI  - Engineering photorespiration: current state and future possibilities.
AB  - Reduction of flux through photorespiration has been viewed as a major way to
      improve crop carbon fixation and yield since the energy-consuming reactions
      associated with this pathway were discovered. This view has been supported by the
      biomasses increases observed in model species that expressed artificial bypass
      reactions to photorespiration. Here, we present an overview about the major
      current attempts to reduce photorespiratory losses in crop species and provide
      suggestions for future research priorities.

PMID- 23121077
TI  - Electronic transition of palladium monoboride.
AB  - The laser-induced fluorescence spectrum of palladium monoboride (PdB) in the
      visible region between 465 and 520 nm has been observed and analyzed. Gas-phase
      PdB molecules were produced by the reaction of diborane (B(2)H(6)) seeded in
      argon with laser ablated palladium atoms. Thirteen vibrational bands have been
      recorded, which included transitions of both Pd(10)B and Pd(11)B isotopic
      species. These bands belong to the [19.7](2)Sigma(+)-X(2)Sigma(+) system, with
      ground X(2)Sigma(+) state bond length, r(o), determined to be 1.7278 A. A
      molecular orbital energy level diagram was used to understand the observed ground
      and excited electronic states. This work represents the first experimental
      investigation of the electronic spectroscopy of the PdB molecule.

PMID- 23121078
TI  - Phosphodiesterase-4 inhibition improves corticosteroid insensitivity in pulmonary
      endothelial cells under oxidative stress.
AB  - BACKGROUND: Several clinical studies have shown that smoking in asthmatics and
      chronic obstructive pulmonary disease patients is closely associated with
      corticosteroid refractoriness. In this work, we have analyzed glucocorticoid
      insensitivity in human pulmonary artery endothelial cells (HPAECs) under
      cigarette smoke extract (CSE) exposure as well as the possible additive effects
      of the combination therapy with a phosphodiesterase (PDE)-4 inhibitor. METHODS:
      Interleukin (IL)-8 was measured in cell supernatants by ELISA. Histone
      deacetylase (HDAC), histone acetylase (HAT), and intracellular cAMP levels were
      measured by colorimetric assays and enzyme immunoassay, respectively. PDE4
      isotypes and glucocorticoid receptor (GR)-alpha and beta expression were measured
      by real-time RT-PCR. RESULTS: The PDE4 inhibitor rolipram dose dependently
      inhibited the IL-8 secretion induced by CSE 5%. In contrast, dexamethasone 1 MUM
      did not show inhibitory effect on IL-8 secretion. Combination of subeffective
      rolipram concentrations at 10 nM increased the inhibitory effect of dexamethasone
      to ~45% of inhibition. Cigarette smoke extract 5% inhibited HDAC activity and
      increased HAT activity generating glucocorticoid insensitivity. Rolipram did not
      modify the HDAC activity, however partially inhibited the increase in HAT
      activity at 1 MUM. PDE4 isotypes were up-regulated by CSE 5% with the consequent
      cAMP down-regulation. Dexamethasone reduced all PDE4 isotypes expression and
      showed additive effects with rolipram enhancing cAMP levels. Furthermore,
      rolipram enhanced GR-alpha expression and inhibited the increase in GR-beta
      induced by CSE. CONCLUSIONS: Combination of rolipram and dexamethasone shows
      additive properties in HPAECs under glucocorticoid insensitive conditions. These
      results may be of potential value in future anti-inflammatory therapies using
      combination of PDE4 inhibitors and glucocorticoids.

PMID- 23121079
TI  - To tell or not to tell - what to do about p.C282Y heterozygotes identified by HFE
      screening.
AB  - Hereditary hemochromatosis (HH) is a common preventable disorder of iron overload
      that can result in liver cirrhosis and reduced lifespan. Most HH is due to
      homozygosity for the HFE p.C282Y substitution. We conducted a study of screening
      for p.C282Y in high schools where p.C282Y heterozygotes (CY) individuals were
      informed of their genotype by letter. We studied whether these individuals
      understood the implications of their genotype, whether this resulted in anxiety
      or reduced health perception and whether cascade testing was higher in families
      of CY than wild-type homozygous (CC) individuals. We found 586 of 5757 (1 in 10)
      screened individuals were CY. One month after receiving their result, 83%
      correctly answered that they have one copy of p.C282Y. There was no adverse
      change in anxiety or health perception from prior to screening to 1 month after
      receiving results. Significantly more family members of CY individuals than CC
      individuals were informed about HH and had testing for HH. In conclusion, we
      found that informing CY individuals of their genotype does not increase anxiety
      and the implications are generally well understood. This leads to cascade testing
      in a minority of families. CY individuals should be informed of their genetic
      status when identified by population screening. 

PMID- 23121080
TI  - Vinpocetine and alpha-tocopherol prevent the increase in DA and oxidative stress
      induced by 3-NPA in striatum isolated nerve endings.
AB  - Vinpocetine is a neuroprotective drug that exerts beneficial effects on
      neurological symptoms and cerebrovascular disease. 3-nitropropionic acid (3-NPA)
      is a toxin that irreversibly inhibits succinate dehydrogenase, the mitochondrial
      enzyme that acts in the electron transport chain at complex II. In previous
      studies in striatum-isolated nerve endings (synaptosomes), we found that
      vinpocetine decreased dopamine (DA) at expense of its main metabolite 3,4
      dihydroxyphenylacetic acid (DOPAC), and that 3-NPA increased DA, reactive oxygen
      species (ROS), DA-quinone products formation, and decreased DOPAC. Therefore, in
      this study, the possible effect of vinpocetine on 3-NPA-induced increase in DA,
      ROS, lipid peroxidation, and DA-quinone products formation in striatum
      synaptosomes were investigated, and compared with the effects of the antioxidant
      alpha-tocopherol. Results show that the increase in DA induced by 3-NPA was
      inhibited by both 25 MUM vinpocetine and 50 MUM alpha-tocopherol. Vinpocetine, as
      alpha-tocopherol, also inhibited 3-NPA-induced increase in ROS (as judged by DCF
      fluorescence), lipid peroxidation (as judged by TBA-RS formation), and DA-quinone
      products formation (as judged by the nitroblue tetrazolium reduction method). As
      in addition to the inhibition of complex II exerted by 3-NPA, 3-NPA increases DA
      oxidation products that in turn can inhibit other sites of the respiratory chain,
      the drop in DA produced by vinpocetine and alpha-tocopherol may importantly
      contribute to their protective action from oxidative damage, particularly in DA
      rich structures.

PMID- 23121081
TI  - Psychological impact of surveillance in patients with a defibrillator lead under
      advisory: a prospective evaluation.
AB  - BACKGROUND: Implantable cardioverter defibrillator (ICD) leads are subject to
      technical failures and the impact of the resulting public advisories on patient
      welfare is unclear. The psychological status of patients who received an advisory
      for their Medtronic Fidelis ICD lead (Medtronic Inc., Minneapolis, MN, USA) and
      followed either by self-surveillance for alarm or home monitoring with CareLink
      was evaluated prospectively and compared to patients with ICDs not under
      advisory. METHODS: One hundred sixty consecutive consenting patients (90 alarms,
      24 Carelinks, 46 controls) were recruited within 1.5 years of advisory
      notification. Advisory patients were seen immediately before being told that the
      automatic lead surveillance utilized since the advisory had been inadequate in
      warning of impending fracture, as well as 1 and 6 months after programming was
      optimized. Depression, anxiety, quality of life (QoL), and ICD-related concerns
      were assessed. RESULTS: Symptoms of depression and state anxiety were experienced
      by 31% and 48% of patients, respectively. QoL was impaired on all subscales. No
      significant group differences in distress and ICD-related concerns emerged at
      baseline or at follow-up. At baseline, alarm patients reported greater
      limitations because of body pain compared to controls (P < 0.05). All patients
      showed a significant reduction in body pain-related QoL at the final versus first
      two evaluations (P < 0.001). Advisory patients were significantly less satisfied
      with surveillance at follow-up than at baseline (P < 0.05). CONCLUSIONS: There
      was limited evidence for worse psychosocial functioning in those at risk for ICD
      lead fracture, irrespective of surveillance method. However, many control and
      advisory patients experienced chronic distress for which counseling may prove
      beneficial.

PMID- 23121082
TI  - Genome size and ploidy of Thysanoptera.
AB  - Flow cytometry was used to study the genome sizes and ploidy levels for four
      thrips species: Franklinothrips orizabensis Johansen (Thysanoptera:
      Aeolothripidae), Frankliniella occidentalis Pergande, Frankliniella fusca Hinds,
      and Thrips tabaci Lindeman (Thysanoptera: Thripidae). F. orizabensis males and
      females had 1C genome sizes of 426 Mb and 422 Mb, respectively. Male and female
      F. fusca had 1C genome sizes of 392 Mb and 409 Mb, whereas F. occidentalis males
      and females had smaller 1C genomes that were 345 Mb and 337 Mb, respectively.
      Male F. orizabensis, F. occidentalis and F. fusca were haploid and females
      diploid. Five isofemale lines of T. tabaci, initiated from parthenogenetic,
      thelytokous females and collected from different locations in North Carolina,
      were included in this study; no males were available. One isofemale line was
      diploid with a genome size of 1C = 310 Mb, and the other four had a mean genome
      size of 1C = 482 Mb, which is consistent with evidence from microsatellite data
      of diploidy and polyploidy, respectively, in these same five thelytokous lines.
      This is the first study to produce genome size estimates for thysanopteran
      species, and report polyploidy in T. tabaci populations.

PMID- 23121083
TI  - Differentiation between deviant trajectory planning, action planning, and reduced
      psychomotor speed in schizophrenia.
AB  - INTRODUCTION: Abnormal psychomotor behaviour in schizophrenia might be based on
      separate deficits. Here we studied the relationship between trajectory planning,
      action planning, psychomotor speed, and indices of cognitive functioning in a
      large group of stabilised patients with schizophrenia. METHOD: Sixty-one patients
      and 30 controls were tested. Trajectory planning was assessed in a graphic task
      in which sequences of single lines, gradually changing in direction, had to be
      drawn. Shifts to a comfortable drawing direction reflect anticipatory trajectory
      planning. Action planning was evaluated in a task in which figures varying in
      complexity and familiarity had to be copied. Psychomotor speed was measured by
      use of a simple line copying task. Measures of information processing speed,
      attention, working memory, and problem solving were derived from
      neuropsychological tests. RESULTS: Patients much more often opted for the unusual
      bottom-to-top direction to draw the vertical lines in the drawing task. They
      changed the line orientation less often than the controls did. In the patient
      group, these trajectory planning indices did not correlate with measures of
      action planning, psychomotor speed, or neuropsychological test scores.
      CONCLUSION: Deviant trajectory planning strongly characterises schizophrenia, and
      is independent from action planning deficits and reduced psychomotor speed.

PMID- 23121084
TI  - Reply 2.

PMID- 23121085
TI  - Review article: a comparison of glucagon-like peptides 1 and 2.
AB  - BACKGROUND: Recent advancements in understanding the roles and functions of
      glucagon-like peptide 1 (GLP-1) and 2 (GLP-2) have provided a basis for targeting
      these peptides in therapeutic strategies. AIM: To summarise the preclinical and
      clinical research supporting the discovery of new therapeutic molecules targeting
      GLP-1 and GLP-2. METHODS: This review is based on a comprehensive PubMed search,
      representing literature published during the past 30 years related to GLP-1 and
      GLP-2. RESULTS: Although produced and secreted together primarily from L cells of
      the intestine in response to ingestion of nutrients, GLP-1 and GLP-2 exhibit
      distinctive biological functions that are governed by the expression of their
      respective receptors, GLP-1R and GLP-2R. Through widespread expression in the
      pancreas, intestine, nervous tissue, et cetera, GLP-1Rs facilitates an incretin
      effect along with effects on appetite and satiety. GLP-1 analogues resistant to
      degradation by dipeptidyl peptidase-IV and inhibitors of dipeptidyl peptidase-IV
      have been developed to aid treatment of diabetes and obesity. The GLP-2R is
      expressed almost exclusively in the stomach and bowel. The most apparent role for
      GLP-2 is its promotion of growth and function of intestinal mucosa, which has
      been targeted for therapies that promote repair and adaptive growth. These are
      used as treatments for intestinal failure and related conditions. CONCLUSIONS:
      Our growing understanding of the biology and function of GLP-1, GLP-2 and
      corresponding receptors has fostered further discovery of fundamental biological
      function as well as new categories of potent therapeutic medicines.

PMID- 23121086
TI  - Bortezomib with high dose melphalan conditioning for autologous transplant is
      safe and effective in patients with heavily pretreated and high risk multiple
      myeloma.
AB  - There are no uniform guidelines for the treatment of relapsed refractory multiple
      myeloma (MM), however autologous stem cell transplant (SCT) remains an important
      treatment modality. Although a number of modifications to high dose melphalan
      (HDM) conditioning have been evaluated, improvement in overall survival has not
      been demonstrated. We now report our experience of 23 patients with heavily
      pretreated MM (median lines of prior treatment 3 [range 1-6]) who underwent SCT
      with bortezomib and high dose melphalan (BorHDM). The overall response rate (at
      least partial response [PR]) was 65.4%. Median overall survival (OS) was 24
      months. A subset of patients who relapsed <= 12 months after initial SCT had
      significantly longer OS after BorHDM SCT compared to a historical control group
      who received HDM conditioning alone (14.5 vs. 8 months, respectively, p = 0.011).
      In summary, BorHDM SCT produces very good response rates in heavily pretreated
      MM, and may increase survival in the salvage setting in patients who relapse
      early after initial SCT. We propose that its use should be explored as part of a
      tandem approach in patients undergoing initial SCT who are at high risk of early
      relapse.

PMID- 23121087
TI  - Sex-dependent associations of genetic variants identified by GWAS with indices of
      adiposity and obesity risk in a Chinese children population.
AB  - OBJECTIVE: Recent genome-wide association studies have identified a few single
      nucleotide polymorphisms (SNPs), which are associated with body mass index
      (BMI)/obesity. This study aimed to examine the identified associations among a
      population of Chinese children. RESEARCH DESIGN AND METHODS: Five SNPs (SEC16B
      rs10913469, SH2B1 rs4788102, PCSK1rs6235, KCTD15 rs29941, BAT2 rs2844479) were
      genotyped for a group of Chinese children (N = 2849, age range 6-18 years). A
      total of 1230 obese cases and 1619 controls with normal weight were identified
      based on the Chinese age- and sex-specific BMI references. RESULTS: Of five
      studied variants, only two (SEC16B rs10913469, SH2B1 rs4788102) were nominally
      associated with indices of adiposity and obesity risk in girls and only SEC16B
      rs10913469 in children at puberty (p < 0.05), while no statistical associations
      was found for three other variants (PCSK1rs6235, KCTD15 rs29941, BAT2 rs2844479).
      After false discovery rate (FDR) adjustment for multiple testing, none were
      statistically significant. Further analysis indicated that the genetic risk score
      (GRS) was associated with BMI, waist circumference and risk of obesity (defined
      by BMI) in girls, even after FDR adjustment for multiple testing. However, there
      was no statistical association of GRS with indices of adiposity and risk of
      obesity in children at puberty after multiple comparison correction. CONCLUSIONS:
      This study confirmed the synthetic effect of SNPs on the indices of adiposity and
      risk of obesity in Chinese girls, but failed to replicate the effect of five
      separate variants. We also did not found cumulative effect of SNPs in children at
      puberty.

PMID- 23121088
TI  - Antioxidant and antiradical SiO2 nanoparticles covalently functionalized with
      gallic acid.
AB  - Gallic acid (GA) and its derivatives are natural polyphenolic substances widely
      used as antioxidants in nutrients, medicine and polymers. Here, nanoantioxidant
      materials are engineered by covalently grafting GA on SiO(2) nanoparticles (NPs).
      A proof-of-concept is provided herein, using four types of well-characterized
      SiO(2) NPs of specific surface area (SSA) 96-352 m(2)/g. All such hybrid SiO(2)
      GA NPs had the same surface density of GA molecules (~1 GA per nm(2)). The
      radical-scavenging capacity (RSC) of the SiO(2)-GA NPs was quantified in
      comparison with pure GA based on the 2,2-diphenyl-1-picrylhydrazyl (DPPH(*))
      radical method, using electron paramagnetic resonance (EPR) and UV-vis
      spectroscopy. The scavenging of DPPH radicals by these nanoantioxidant SiO(2)-GA
      NPs showed mixed-phase kinetics: An initial fast-phase (t(1/2) <1 min)
      corresponding to a H-Atom Transfer (HAT) mechanism, followed by a slow-phase
      attributed to secondary radical-radical reactions. The slow-reactions resulted in
      radical-induced NP agglomeration, that was more prominent for high-SSA NPs. After
      their interaction with DPPH radicals, the nanoantioxidant particles can be reused
      by simple washing with no impairment of their RSC.

PMID- 23121089
TI  - Postpartum infections: occurrence, healthcare contacts and association with
      breastfeeding.
AB  - OBJECTIVE: To investigate the following: (i) the occurrence of postpartum
      infections; (ii) the frequency of contact with either a general practitioner or a
      hospital due to postpartum infections; and (iii) the association of postpartum
      infections with continuation of breastfeeding. DESIGN: Cross-sectional study.
      SETTING: Department of Gynecology and Obstetrics Horsens Hospital, Horsens,
      Denmark. POPULATION: A total of 1871 women who gave birth at a regional hospital
      in Denmark over a one-year period (2007-2008). METHODS: Data were collected by a
      questionnaire given to the women and combined with data from general practitioner
      and hospital records. MAIN OUTCOME MEASURES: The distribution of different
      infections, as well as the overall occurrence of any infection, was evaluated
      according to mode of delivery and breastfeeding status (stopped/continued).
      RESULTS: Within four weeks after delivery, 24% of all women had experienced one
      or more self-reported episode of infection. Breast infections (12%) were most
      frequent, followed by wound (3%), airway (3%), vaginal (3%) and urinary tract
      infections (3%), endometritis (2%) and "other infections" (2%). Of the women with
      an infection, 66% (265 of 395) contacted their general practitioner, while 9% (37
      of 395) had contact with a hospital. A significantly larger proportion of women
      with a postpartum infection stopped breastfeeding (21%) within the first four
      weeks after delivery compared with women without infection (12%; p < 0.001).
      CONCLUSIONS: Postpartum infections were common, and the occurrence is likely to
      be underestimated if based on hospital medical records only. Infection was
      associated with higher rates of discontinuation of breastfeeding.

PMID- 23121090
TI  - Radical cascades initiated by intermolecular radical addition to alkynes and
      related triple bond systems.

PMID- 23121091
TI  - A modeller's perspective on infection dynamics within and between hosts.
AB  - The goal of this case-series was to increase our understanding of some complex
      within and between-host infection dynamics through the creation of mathematical
      and computational models that are able to capture the existing host and/or
      parasite heterogeneity. This goal was reached through a series of research
      projects (regarding experimental autoimmune encephalomyelitis (EAE) in mice,
      Mycobacterium avium subspecies paratuberculosis infection in cattle, Eimeria
      acervulina infection in chicken and human malaria) that gradually build up in
      complexity of both the system modelled and the modelling techniques used. In this
      case-series, the vast majority of model components have a direct link with
      reality. The results have shown some detailed examples of the valuable
      contribution that models have in understanding infection processes. The most
      satisfying achievements have come from those models that were able to, in
      hindsight, make complicated experimental results seem obvious and logical, and
      where the process of building the model was as insightful as the final results.
      The models created in these projects help to explain a wide range of sometimes
      contradictory experimental results and are used to predict the effect of control
      measures. In addition, they generate ideas for the development of new methods of
      control.

PMID- 23121092
TI  - BODIPY-based ratiometric fluorescent sensor for highly selective detection of
      glutathione over cysteine and homocysteine.
AB  - We report a ratiometric fluorescent sensor based on monochlorinated BODIPY for
      highly selective detection of glutathione (GSH) over cysteine (Cys)/homocysteine
      (Hcy). The chlorine of the monochlorinated BODIPY can be rapidly replaced by
      thiolates of biothiols through thiol-halogen nucleophilic substitution. The amino
      groups of Cys/Hcy but not GSH further replace the thiolate to form amino
      substituted BODIPY. The significantly different photophysical properties of
      sulfur- and amino-substituted BODIPY enable the discrimination of GSH over Cys
      and Hcy. The sensor was applied for detection of GSH in living cells.

PMID- 23121093
TI  - RGG repeats of PrP-like Shadoo protein bind nucleic acids.
AB  - Shadoo (Sho) is a central nervous system glycoprotein with characteristics
      similar to those of the cellular prion protein PrP(C), each containing a highly
      conserved hydrophobic domain (HD) and an N-terminal repeat region. Whereas PrP(C)
      includes histidine-containing octarepeats, the Sho region N-terminal to the HD
      includes tandem positively charged "RGG boxes", predicted to bind RNA. Here, we
      demonstrate that Sho binds DNA and RNA in vitro via this arginine-rich region.

PMID- 23121094
TI  - Age and risk factors influence the microbial aetiology of bloodstream infection
      in children.
AB  - AIM: To study the aetiology of bloodstream infections (BSI) in children 0-17
      years, the influence of age and underlying co-morbidity on BSI rate, distribution
      of pathogens and outcome; and to provide data on antimicrobial susceptibility
      patterns. METHODS: A retrospective population-based study. Data on blood cultures
      were collected at yearly intervals during 1998-2008. Information about risk
      factors, focal infection and outcome was retrieved from the patient charts.
      RESULTS: We identified 1097 BSI. The incidence of BSI was 0.4/1000. The age
      specific incidence was 2.3/1000 in neonates (0-28 days old) and 0.2/1000 in the
      age group 6-17 years. Staphylococcus aureus was the most common pathogen. The
      number of species causing BSI in previously healthy children was lower compared
      with children with co-morbidity. Most children requiring intensive care had a
      serious underlying illness. Antimicrobial resistance was rare and did not
      influence outcome. The case-fatality rate was 14.4% in neonates, 5.4% in children
      with co-morbidity and 1.7% in previously healthy children. CONCLUSION: Mortality
      from BSI is low, and a limited spectrum of pathogens is isolated from previously
      healthy children compared with children with co-morbidity. When choosing
      empirical therapy for suspected BSI, age and presence of risk factors should be
      taken into account.

PMID- 23121095
TI  - Characteristics of HPV infection over time in European women who are HIV-1
      positive.
AB  - OBJECTIVE: The objectives of the study were to investigate high-risk human
      papillomavirus (HR-HPV) infection and type distribution in women infected with
      HIV-1, and to determine the relevance of HR-HPV positivity and persistence/loss
      to the development of high-grade cervical disease. DESIGN: A total of 518
      European women infected with HIV attending for routine gynaecological care
      consented to 6-monthly follow-up visits over 3 years, with surveillance of
      cytology, colposcopy and histopathology, where relevant, and longer follow-up,
      where possible. SETTING: European women infected with HIV attending for routine
      gynaecological care. POPULATION OR SAMPLE: 518 European women infected with HIV
      attending for gynaecological care in 6 hospital-based European centres - Dublin,
      Edinburgh, London, Milan, Paris, and Warsaw. METHODS: Cervical screening was
      achieved by liquid-based cytology (LBC) of brush samples in PreservCyt(r) medium.
      The HPV testing of residual samples was performed by Hybrid-Capture II, with
      genotyping of positives using the HPV Line Blot Assay. Histology results were
      accessed where available. MAIN OUTCOME MEASURES: Description of high risk human
      papillomavirus (HR-HPV) infection and type distribution in HIV-1 infected women.
      RESULTS: The estimated prevalence at baseline of any HR-HPV type was 49.5% (46.3
      52.8%): 10.2% for HPV 16 and 4.3% for HPV 18. The prevalence increased with
      increasing immunosuppression. Multiple infections were detected in 26.8%. HR-HPV
      genotypes were detected in 34.9% of cases with normal cytology, in 77.2% of cases
      with atypical squamous cells of undetermined significance/low-grade squamous
      intraepithelial lesion (ASCUS/LSIL) and in 90.8% of cases with high-grade SIL
      (HSIL). The prevalence of HPV 16 in HSIL was 38.5%, with the three most common
      types thereafter having prevalence rates of 19.2% (HPV 58), 19.2% (HPV 53) and
      16.6% (HPV 52). The overall persistence of any high-risk type was 55.8%. We found
      that 6 months persistence of HPV 16 occurred in 24 women. Seven cases of high
      grade cervical disease developed, and all were associated with initial/persistent
      HR-HPV positivity. CONCLUSIONS: A wide diversity of HPV types was evident, and
      multiple infections were common. Detection or persistence of any HR-HPV was
      associated with a very low incidence of subsequent high-grade disease.

PMID- 23121096
TI  - Ion channels as therapeutic targets: a drug discovery perspective.
AB  - Ion channels are membrane proteins expressed in almost all living cells. The
      sequencing of the human genome has identified more than 400 putative ion
      channels, but only a fraction of these have been cloned and functionally tested.
      The widespread tissue distribution of ion channels, coupled with the plethora of
      physiological consequences of their opening and closing, makes ion-channel
      targeted drug discovery highly compelling. However, despite some important drugs
      in clinical use today, as a class, ion channels remain underexploited in drug
      discovery and many existing drugs are poorly selective with significant
      toxicities or suboptimal efficacy. This Perspective seeks to review the ion
      channel family, its structural and functional features, and the diseases that are
      known to be modulated by members of the family. In particular, we will explore
      the structure and properties of known ligands and consider the future prospects
      for drug discovery in this challenging but high potential area.

PMID- 23121097
TI  - Putting flesh on the bones: DCC combines membrane insertion with cytoskeletal
      reorganization to promote chemoattraction (commentary on Cotrufo et al.).

PMID- 23121098
TI  - The 1 3A' HCN and 1 3A' HCO+ vibrational frequencies and spectroscopic constants
      from quartic force fields.
AB  - Building on previous studies involving coupled cluster quartic force fields for
      the description of spectroscopic constants and vibrational frequencies of
      astronomically relevant molecules, this work applies the same techniques to the
      elucidation of such properties for the bent 1 (3)A' state of HCN and the
      isoelectronic 1 (3)A' HCO(+). Core correlation is treated both by explicit means
      and as a correction. Each approach gives closely comparable spectroscopic
      constants and vibrational frequencies once more, indicating that the composite
      method is a viable and less costly alternative. We are providing fundamental
      vibrational frequencies for these systems where agreement with experiment in
      previous studies has been within 4 cm(-1) or better. Frequencies for the first
      overtones and combination bands as well as various spectroscopic constants are
      also reported. 

PMID- 23121099
TI  - Growth differentiation factor 5 modulation of chondrogenesis of self-assembled
      constructs involves gap junction-mediated intercellular communication.
AB  - A novel scaffold-free self-assembled cartilage construct has been generated and
      used to repair particular chondral defects effectively. However, the mechanisms
      related to the construction of these self-assembled cartilages have not yet been
      fully elucidated. We hypothesize that gap junction intercellular communication
      (GJIC) plays a critical role in the development of self-assembled constructs upon
      GDF-5 induction. In this study, we investigated the effect of connexin 43 (C*43)
      mediated GJIC on GDF-5 modulation of chondrogenesis from two aspects, cell
      monolayer culture and 3-D self-assembly culture. We induced cells or self
      assembled constructs with chondrogenic media (CM), growth differentiation factor
      5 (GDF-5) or 1-heptanol for 3 weeks. At the end of that time, the results of
      quantitative fluorescence redistribution after photobleaching (FRAP) assay and
      immunofluorescence demonstrated that GDF-5 improved both GJIC and chondrogenic
      differentiation to a significant degree while 1-heptanol nearly offset the
      expected improvements in chondrogenesis. Biochemical assay and histology showed
      that GDF-5 can obviously enhance GAG, C*43 and type II collagen expressions.
      Conversely, we also showed that while 1-heptanol weakened GAG and type II
      collagen expression in self-assembled constructs, it had no effect on C*43
      expression. Furthermore, real-time polymerase chain reaction showed that GDF-5
      enhanced GAG and type II collagen transcription while 1-heptanol reduced them,
      but was affectless on C*43 transcription. This suggests that the generation of
      scaffold-free self-assembled cartilage from human mesenchymal stem cells upon GDF
      5 induction may be mediated, at least in part, via the modulation of GJIC.

PMID- 23121100
TI  - Contemporary challenges in the prevention and management of pulmonary embolism.

PMID- 23121102
TI  - Laparoscopic image(s) of pneumothorax in repair of massive hiatus hernia.

PMID- 23121103
TI  - Biliary cast syndrome after liver transplantation.

PMID- 23121104
TI  - Unusually complicated chest infection: colon containing intercostal hernia.

PMID- 23121105
TI  - Giant obturator schwannoma: an unusual finding in a patient with prostate cancer.

PMID- 23121106
TI  - Penile fracture: second episode in 5 years.

PMID- 23121107
TI  - Meningioma compressing the premotor cortex misdiagnosed for a stroke.

PMID- 23121108
TI  - It is not just about chest tubes (Re: ANZ J. Surg. 2012; 82: 392-4).

PMID- 23121109
TI  - Juvenile hormone III suppresses forkhead of transcription factor in the fat body
      and reduces fat accumulation in the diapausing mosquito, Culex pipiens.
AB  - Juvenile hormone (JH) controls diverse physiological and developmental events
      including diapause and nutrient metabolism. The focal point of endocrine
      regulation in adult reproductive diapause is initiated by a halt of JH synthesis.
      In diapausing females of the mosquito Culex pipiens, the other key molecular
      event is the signalling pathway from insulin to forkhead of transcription factor
      (FOXO). We hypothesized that a halt of JH synthesis is related to activation of
      FOXO, which results in increasing lipid reserves in the fat body at the onset of
      the diapause programme. In this study, the full-length sequence of the foxo gene
      in C. pipiens was characterized, and the protein abundance pattern of the foxo
      gene product was analyzed by immunoblotting and immunohistochemistry. FOXO was
      much more abundant in the fat body of diapausing females than in the fat body of
      nondiapausing females; much lower levels were present in other adult tissues.
      When we topically applied JH III to diapause-destined females, FOXO was
      suppressed, and fat accumulation was reduced, suggesting an interaction between
      JH synthesis and FOXO that is critical for expression of the diapause phenotype.

PMID- 23121110
TI  - Associations between risk perceptions and worry about common diseases: a between-
      and within-subjects examination.
AB  - The relationships between worry and perceptions of likelihood and severity were
      evaluated across eight common diseases. Individual and disease variability in
      worry and perceptions were examined. 294 participants were recruited through the
      Multiplex Initiative, in which a genetic susceptibility test for eight common
      diseases was offered to healthy adults. Participants completed a baseline
      telephone survey and web-based surveys without a commitment to be tested, and
      then made a choice on testing. Between- and within-subjects analyses yielded the
      following main findings: (1) worry is more closely related to likelihood
      perceptions than to severity perceptions; (2) severity perceptions add
      significantly to explained worry variances above and beyond likelihood
      perceptions; (3) risk perceptions and worries form two clusters: cancer diseases
      and cardiovascular-metabolic diseases; and (4) variance in risk perception and
      worry is explained by a combination of between- and within-subjects variances.
      Risk perception research should attend to severity perceptions, within-subjects
      variability and inter-disease differences, and to strategies for grouping
      conditions.

PMID- 23121111
TI  - Pacing system malfunction is a rare cause of hospital admission for syncope in
      patients with a permanent pacemaker.
AB  - BACKGROUND: Few studies have examined the prevalence of permanent pacemaker (PPM)
      malfunction among patients with a previously implanted pacemaker admitted to the
      hospital with syncope. OBJECTIVE: This study sought to examine causes of syncope
      in patients with a previously implanted pacemaker admitted to our hospital with
      syncope. METHODS: We retrospectively reviewed our hospital admission database for
      patients who had both keywords "syncope" and "pacemaker" as their diagnoses from
      January 1, 1995 until June 1, 2012. One hundred and sixty-two patients who were
      admitted to the hospital because of syncope and had a PPM implanted prior to the
      index syncopal episode were included. All patients had pacemakers interrogated
      during the admission. Two independent physicians examined the discharge summary
      of each patient and determined the cause of syncope in each case. RESULTS: Of the
      162 patients studied, eight (4.9%) were found to have pacemaker system
      malfunction as a cause of syncope. In 96 patients (59.2%), the cause of syncope
      could not be determined prior to hospital discharge. Among the identifiable
      causes of syncope, orthostatic hypotension was most prevalent (16%) followed by
      vasovagal (6%), severe aortic stenosis (4.3%), atrial arrhythmia (3.1%), acute
      and subacute infection (3.1%), and other less prevalent causes (3.1%).
      CONCLUSION: In this study, PPM system malfunction was rarely a cause of syncope
      in patients admitted to the hospital with a previously implanted device.

PMID- 23121112
TI  - Mesenchymal stem cells regulate epithelial-mesenchymal transition and tumor
      progression of pancreatic cancer cells.
AB  - Cancer-associated fibroblasts contribute to cancer progression that is caused by
      epithelial-mesenchymal transition (EMT). Recently, mesenchymal stem cells (MSCs)
      were found to be the major candidate involved in the development of tumor
      promoting cancer stroma. Here we report that alpha-smooth muscle actin-positive
      myofibroblast-like cells originating from MSCs contribute to inducing EMT in side
      population cells of pancreatic cancer. More importantly, MSC-derived
      myofibroblasts function to maintain tumor-initiating stem cell-like
      characteristics, including augmenting expression levels of various stemness
      associated genes, enhancing sphere- forming activity, promoting tumor formation
      in a mouse xenograft model, and showing resistance to anticancer drugs.
      Furthermore, both gamma-secretase inhibitor and siRNA directed against Jagged-1
      attenuated MSC-associated E-cadherin suppression and sphere formation in
      pancreatic cancer side population cells. Thus, our results suggest that MSC
      derived myofibroblasts play important roles in regulating EMT and tumor
      initiating stem cell-like properties of pancreatic cancer cells through an
      intermediating Notch signal.

PMID- 23121113
TI  - Transcardiac cerebral angiography in a child.
AB  - The authors present a case in which transfemoral venous, transcardiac cerebral
      angiography was performed. In this 5-year-old girl with PHACE syndrome, both
      transfemoral and transbrachial arterial routes could not be used due to aortic
      interruption and aneurysmal dilation and small looping of the proximal portion of
      bilateral subclavian arteries. A 5-F balloon-tipped double-lumen catheter was
      advanced to the right atrium of the heart from the femoral vein. The catheter was
      then advanced to the left atrium through the patent foramen ovale and was further
      advanced to the left ventricle and then to the ascending aorta. The balloon
      catheter was exchanged for a 4-F catheter. Bilateral common carotid angiography
      was performed without difficulty. This transcardiac approach is useful in the
      unusual situation in which both femoral and brachial arterial routes are not
      available.

PMID- 23121114
TI  - The assessment of bulging fontanel and splitting of sutures in premature infants:
      an interrater reliability study by the Hydrocephalus Clinical Research Network.
AB  - OBJECT: Previous studies from the Hydrocephalus Clinical Research Network (HCRN)
      have shown a great degree of variation in surgical decision making for infants
      with posthemorrhagic hydrocephalus, such as when to temporize, when to shunt, or
      when to convert. Since much of this clinical decision making is dictated by
      clinical signs of increased intracranial pressure (including bulging fontanel and
      splitting of sutures), the authors investigated whether there was variability in
      how these signs were being assessed by neurosurgeons. They wanted to answer the
      following question: is there acceptable interrater reliability in the
      neurosurgical assessment of bulging fontanel and split sutures? METHODS: Explicit
      written definitions of "bulging fontanel" and "split sutures" were agreed upon
      with consensus across the HCRN. At 5 HCRN centers, pairs of neurosurgeons
      independently assessed premature infants in the first 3 months of life for the
      presence of a split suture and/or bulging fontanel, according to the a priori
      definitions. Interrater reliability was then calculated between pairs of
      observers using the Cohen simple kappa coefficient. Institutional board review
      approval was obtained at each center and at the University of Utah Data
      Coordinating Center. RESULTS: A total of 38 infants were assessed by 13 different
      raters (10 faculty, 2 fellows, and 1 resident). The kappa for bulging fontanel
      was 0.65 (95% CI 0.41-0.90), and the kappa for split sutures was 0.84 (95% CI
      0.66-1.0). No complications from the study were encountered. CONCLUSIONS: The
      authors have found a high degree of interrater reliability among neurosurgeons in
      their assessment of bulging fontanel and split sutures. While decision making may
      vary, the clinical assessment of this cohort appears to be consistent among these
      physicians, which is crucial for prospective studies moving forward.

PMID- 23121115
TI  - Tumors of the superior medullary velum in infancy and childhood: report of 6
      cases.
AB  - OBJECT: The superior medullary velum (SMV) is a thin lamina of white matter
      located between the superior cerebellar peduncles horizontally and between the
      midbrain and cerebellum vertically. The SMV has not previously been described as
      the primary location of a posterior fossa tumor, although it can be secondarily
      invaded by a tumor from the cerebellum or quadrigeminal plate. This paper aims to
      define clinical and radiological features of tumors primarily arising from the
      SMV during childhood. METHODS: The authors observed 6 infants and children
      harboring neoplasms of the SMV who were treated at Ann & Robert Lurie Children's
      Hospital of Chicago (formerly Children's Memorial Hospital) in Chicago, Illinois.
      Pathological diagnosis of the neoplasms was an atypical teratoid/rhabdoid tumor
      (ATRT) in 5 patients, and a juvenile pilocytic astrocytoma (JPA) in the remaining
      child. The tumors were diagnosed during infancy in all patients, with ages
      ranging from 3 months to 10 months, except for the patient with a JPA (diagnosed
      at 5 years old). All patients presented with signs and symptoms of increased
      intracranial pressure due to obstructive hydrocephalus. RESULTS: Characteristic
      MRI features were noted, consistent with a mass in both the fourth ventricle and
      the cerebellomesencephalic fissure and quadrigeminal cistern, resulting in the
      circumferential displacement of the neural structures surrounding the SMV. The
      tumor was removed effectively in gross-total fashion through the occipital
      transtentorial approach in all patients. This approach offers a wide exposure of
      the region. However, all infants with ATRT suffered tumor dissemination and died
      between 4 and 11 months after diagnosis, in spite of radical resection and
      oncological treatment. The 1 child with JPA is alive and well 30 months after
      tumor resection. CONCLUSIONS: To the best of the authors' knowledge, this is the
      first description in the literature that focuses on tumors originating from the
      SMV. This entity must be promptly recognized on preoperative radiological studies
      to carefully plan the subsequent surgical and clinical management.

PMID- 23121116
TI  - Recombinant human C1 inhibitor for the prophylaxis of hereditary angioedema
      attacks: a pilot study.
AB  - BACKGROUND: Hereditary angioedema (HAE) is a disease characterized by recurrent
      tissue swelling affecting various body locations. Recent literature shows that
      patients with frequent attacks may benefit from long-term prophylaxis. This study
      evaluated the safety and prophylactic effect of weekly administrations of
      recombinant C1INH (rhC1INH). METHODS: Patients with a history of HAE attacks
      occurring >=every 2 weeks received a once weekly administration of 50 U/kg
      rhC1INH. Hereditary angioedema attack history was collected at screening.
      Breakthrough attacks during the study were recorded at each visit. Following a 2
      week run-in period, HAE patients received 8 weekly rhC1INH administrations and
      were followed-up for an additional 6 weeks. Efficacy was evaluated by comparing
      the HAE attack incidence during the treatment period to the historical attacks
      over the previous 2 years. Safety evaluation was based on clinical laboratory and
      adverse events (AEs) reports. RESULTS: The 25 participants reported a mean of 0.9
      attacks/week over the past 2 years. The mean breakthrough attack rate during the
      treatment period was 0.4 attacks/week (95% CI 0.28-0.56). A total of 30 treatment
      emergent-AEs were reported in 13 patients, all mild to moderate. One patient died
      from a laryngeal attack 25 days after last study drug administration. The only
      possible drug related AEs reported were dry mouth, dizziness and anxiety in one
      patient and hypotension in another. There were no allergic AEs and no
      neutralizing antibodies observed. CONCLUSIONS: Weekly administrations of 50 U/kg
      rhC1INH appeared to reduce the frequency of HAE attacks and were generally safe
      and well tolerated.

PMID- 23121117
TI  - Review article: herbal and dietary supplement hepatotoxicity.
AB  - BACKGROUND: Herbal and dietary supplements are commonly used throughout the
      World. There is a tendency for underreporting their ingestion by patients and the
      magnitude of their use is underrecognised by Physicians. Herbal hepatotoxicity is
      not uncommonly encountered, but the precise incidence and manifestations have not
      been well characterised. AIMS: To review the epidemiology, presentation and
      diagnosis of herbal hepatotoxicity. This review will mainly discuss single
      ingredients and complex mixtures of herbs marketed under a single label. METHODS:
      A Medline search was undertaken to identify relevant literature using search
      terms including 'herbal', 'herbs', 'dietary supplement', 'liver injury',
      'hepatitis' and 'hepatotoxicity'. Furthermore, we scanned the reference lists of
      the primary and review articles to identify publications not retrieved by
      electronic searches. RESULTS: The incidence rates of herbal hepatotoxicity are
      largely unknown. The clinical presentation and severity can be highly variable,
      ranging from mild hepatitis to acute hepatic failure requiring transplantation.
      Scoring systems for the causality assessment of drug-induced liver injury may be
      helpful, but have not been validated for herbal hepatotoxicity. Hepatotoxicity
      features of commonly used herbal products, such as Ayurvedic and Chinese herbs,
      black cohosh, chaparral, germander, greater celandine, green tea, Herbalife,
      Hydroxycut, kava, pennyroyal, pyrrolizidine alkaloids, skullcap, and usnic acid,
      have been individually reviewed. Furthermore, clinically significant herb-drug
      interactions are also discussed. CONCLUSIONS: A number of herbal medicinal
      products are associated with a spectrum of hepatotoxicity events. Advances in the
      understanding of the pathogenesis and the risks involved are needed to improve
      herbal medicine safety.

PMID- 23121118
TI  - The relationship of religious involvement indicators and social support to
      current and past suicidality among depressed older adults.
AB  - Elderly people, particularly those with major depression, are at the highest risk
      for suicide than any other age group. Religious involvement is associated with a
      range of health outcomes including lower odds of death by suicide. However, not
      much is known about the effects of religious involvement on suicidal ideation in
      the elderly or which aspects of religiosity are beneficial. This study examined
      the relative influence of various conceptualizations of religious involvement,
      above and beyond the protective effects of social support, on current and past
      suicidality among depressed older adults. Participants were 248 depressed
      patients, 59 years and older, enrolled in the Neurocognitive Outcomes of
      Depression in the Elderly study. A psychiatrist assessed current suicidal
      ideation using the suicidal thoughts item from the Montgomery-Asberg Depression
      Rating Scale. Past history of suicide attempts, four religious involvement
      indicators, social support indicators, and control variables were assessed via
      self-report. Church attendance, above and beyond importance of religion, private
      religious practices, and social support, was associated with less suicidal
      ideation; perceived social support partially mediated this relationship. Current
      religious practices were not predictive of retrospective reports of past suicide
      attempts. Church attendance, rather than other religious involvement indicators,
      has the strongest relationship to current suicidal ideation. Clinicians should
      consider public religious activity patterns and perceived social support when
      assessing for other known risk and protective factors for suicide and in
      developing treatment plans.

PMID- 23121119
TI  - Multiple tyrosine residues at the GABA binding pocket influence surface
      expression and mediate kinetics of the GABAA receptor.
AB  - The prevalence of aromatic residues in the ligand binding site of the GABA(A) 
      receptor, as with other cys-loop ligand-gated ion channels, is undoubtedly
      important for the ability of neurotransmitters to bind and trigger channel
      opening. Here, we have examined three conserved tyrosine residues at the GABA
      binding pocket (beta(2) Tyr97, beta(2) Tyr157, and beta(2) Tyr205), making
      mutations to alanine and phenylalanine. We fully characterized the effects each
      mutation had on receptor function using heterologous expression in HEK-293 cells,
      which included examining surface expression, kinetics of macroscopic currents,
      microscopic binding and unbinding rates for an antagonist, and microscopic
      binding rates for an agonist. The assembly or trafficking of GABA(A)  receptors
      was disrupted when tyrosine mutants were expressed as alphabeta receptors, but
      interestingly not when expressed as alphabetagamma receptors. Mutation of each
      tyrosine accelerated deactivation and slowed GABA binding. This provides strong
      evidence that these residues influence the binding of GABA. Qualitatively,
      mutation of each tyrosine has a very similar effect on receptor function;
      however, mutations at beta(2) Tyr157 and beta(2) Tyr205 are more detrimental than
      beta(2) Tyr97 mutations, particularly to the GABA binding rate. Overall, the
      results suggest that interactions involving multiple tyrosine residues are likely
      during the binding process.

PMID- 23121120
TI  - Unzipped multiwalled carbon nanotube oxide/multiwalled carbon nanotube hybrids
      for polymer reinforcement.
AB  - Multiwalled carbon nanotubes (MWNTs) have been widely used as nanofillers for
      polymer reinforcement. However, it has been restricted by the limited available
      interface area of MWNTs in the polymer matrices. Oxidation unzipping of MWNTs is
      an effective way to solve this problem. The unzipped multiwalled carbon nanotube
      oxides (UMCNOs) exhibit excellent enhancement effect with low weight fractions,
      but agglomeration of UMCNOs at a relatively higher loading still hampered the
      mechanical reinforcement of polymer composites. In this paper, we interestingly
      found that the dispersion of UMCNOs in polymer matrices can be significantly
      improved with the combination of pristine MWNTs. The hybrids of MWNTs and UMCNOs
      (U/Ms) can be easily obtained by adding the pristine MWNTs into the UMCNOs
      aqueous dispersion, followed by sonication. With a pi-stacking interaction, the
      UMCNOs were attached onto the outwalls of MWNTs. The morphologies and structure
      of the U/Ms were characterized by several measurements. The mechanical testing of
      the resultant poly(vinyl alcohol) (PVA)-based composites demonstrated that the
      U/Ms can be used as ideal reinforcing fillers. Compared to PVA, the yield
      strength and Young's modulus of U/M-PVA composites with a loading of 0.7 wt % of
      the U/Ms approached ~145.8 MPa and 6.9 GPa, respectively, which are increases of
      ~107.4% and ~122.5%, respectively. The results of tensile tests demonstrated that
      the reinforcement effect of U/Ms is superior to the individual UMCNOs and MWNTs,
      because of the synergistic interaction of UMCNOs and MWNTs.

PMID- 23121122
TI  - Dimensionality transformation through paddlewheel reconfiguration in a flexible
      and porous Zn-based metal-organic framework.
AB  - The reaction between Zn and a pyrene-based ligand decorated with benzoate
      fragments (H(4)TBAPy) yields a 2D layered porous network with the metal
      coordination based on a paddlewheel motif. Upon desolvation, the structure
      undergoes a significant and reversible structural adjustment with a corresponding
      reduction in crystallinity. The combination of computationally assisted structure
      determination and experimental data analysis of the desolvated phase revealed a
      structural change in the metal coordination geometry from square-pyramidal to
      tetrahedral. Simulations of desolvation showed that the local distortion of the
      ligand geometry followed by the rotation and displacement of the pyrene core
      permits the breakup of the metal-paddlewheel motifs and the formation of 1D Zn-O
      chains that cross-link adjacent layers, resulting in a dimensionality change from
      the 2D layered structure to a 3D structure. Constrained Rietveld refinement of
      the powder X-ray diffraction pattern of the desolvated phase and the use of other
      analytical techniques such as porosity measurements, (13)C CP MAS NMR
      spectroscopy, and fluorescence spectroscopy strongly supported the observed
      structural transformation. The 3D network is stable up to 425  degrees C and is
      permanently porous to CO(2) with an apparent BET surface area of 523(8) m(2)/g
      (p/p degrees  = 0.02-0.22). Because of the hydrophobic nature, size, and shape of
      the pores of the 3D framework, the adsorption behavior of the structure toward p
      xylene and m-xylene was studied, and the results indicated that the shape of the
      isotherm and the kinetics of the adsorption process are determined mainly by the
      shape of the xylene isomers, with each xylene isomer interacting with the host
      framework in a different manner.

PMID- 23121123
TI  - The role of obesity and type 2 diabetes mellitus in the development of male
      obesity-associated secondary hypogonadism.
AB  - Obesity, secondary (hypogonadotrophic) hypogonadism (SH), sleep disorders [such
      as obstructive sleep apnoea (OSA)] and type 2 diabetes mellitus (T2DM) in men
      have complex interlinks both with respect to mutual aetiopathogenesis as well as
      therapeutics. Correction of the attendant hypogonadism in obese men may serve to
      break this link and have beneficial effects beyond restoration of normal sexual
      function. Male obesity-associated secondary hypogonadism (MOSH) should be
      regarded as a distinct clinical entity and subtype of SH. A high index of
      suspicion for the presence of MOSH must be maintained by clinicians when
      assessing obese men. The pathogenesis of MOSH remains incompletely understood.
      Furthermore, the optimal management of MOSH and its associated sequelae will
      require long-term prospective studies that in turn will inform the development of
      future clinical guidelines for this important and prevalent condition.

PMID- 23121124
TI  - Benzyl benzoate glycosides from Oligoneuron rigidum.
AB  - Two new benzyl benzoate glycosides were isolated from the leaves and stems of the
      native North American prairie plant Oligoneuron rigidum (stiff goldenrod). The
      glycosides were isolated as a mixture of benzoate and acetate esters, which were
      subjected to mild base hydrolysis to facilitate full structural characterization
      using LCMSMS and 1D and 2D NMR data. 

PMID- 23121125
TI  - Endothelial FOS expression and pre-eclampsia.
AB  - OBJECTIVE: To study gene expression profiles in human endothelial cells incubated
      with plasma from women who developed pre-eclampsia and women with normotensive
      pregnancies. DESIGN: A case-control study. SETTING: A longitudinal nested case
      control study within three maternity units. POPULATION: A mixed obstetric
      population attending maternity hospitals in Glasgow. METHODS: Plasma was obtained
      at both 16 and 28 weeks of gestation from 12 women: six women subsequently
      developed pre-eclampsia (cases) and six women, matched for age, body mass index
      (BMI) and parity, remained normotensive (controls). Human umbilical vein
      endothelial cells (HUVECs) were incubated with plasma for 24 hour before RNA
      isolation. MAIN OUTCOME MEASURES: Gene expression profiles were compared between
      the two gestational time points using Illumina((r)) HumanHT-12 v4 Expression
      BeadChips. Differential mRNA expression observed in microarray experiments were
      validated using quantitative real-time reverse transcription polymerase chain
      reaction (qRT-PCR), and gene networks were analysed using Ingenuity((r)) pathway
      analysis. RESULTS: There was a significant difference in the expression of 25
      genes following incubation with plasma from controls, and an increase in the
      expression of 11 genes following incubation with plasma from cases, with no
      overlap between the two groups (false discovery rate, FDR < 0.05). There was a
      3.74-fold (FDR < 0.001) increase in the expression of the c-Fos gene (FOS) when
      HUVECs were incubated with control plasma from 16 and 28 weeks of gestation, with
      no significant difference between the two time points with plasma from cases.
      Similar findings for FOS were obtained by qRT-PCR. CONCLUSIONS: Plasma from women
      who subsequently develop pre-eclampsia appears to contain factors that lead to
      the dysregulation of FOS in endothelial cells during pregnancy. Reduced
      expression of c-Fos may lead to impaired vasculogenesis, and thereby contribute
      to the development of pre-eclampsia.

PMID- 23121126
TI  - Eating problems in young children -- a population-based study.
AB  - AIM: To analyse the prevalence of atypical eating problems and their associations
      with anxious or oppositional behaviours in young children. METHODS: One thousand
      and ninety children examined in the school enrolment test in a defined
      geographical region were included (544 boys). The parents completed a 25-item
      questionnaire regarding their child's eating behaviour and anxious or
      oppositional behaviours. RESULTS: Half of the parents reported that their child
      avoids certain foods (53%). Twenty-three percent showed selective eating, 26%
      showed an aversion against new foods. Children with underweight avoided more
      types of food and ate smaller amounts than children with normal or overweight.
      Three groups could be differentiated. Sixty-one percent of the children were
      'normal eaters' with avoidance of certain foods, normal weight status and low
      anxious or oppositional behaviour. Thirty-four percent showed selective and/or
      restrictive eating, and 5% worried about their weight. Children with selective
      eating and with weight concerns were more often affected by anxious and
      oppositional behaviours. CONCLUSION: Atypical eating problems are common in young
      children. Without accompanying weight loss, behavioural or emotional problems,
      selective eating should be seen as a normal feature in young eating behaviour.
      Parents of young children with selective, restrictive eating or with weight
      worrying and psychological problems should be offered advice/treatment.

PMID- 23121127
TI  - A case of dilated cardiomyopathy.
AB  - CONTEXT: Dilated cardiomyopathy is a significant health problem in Africa.
      Diagnosis and treatment can be challenging as it frequently affects young
      patients and those without risk factors for cardiac disease. ISSUE: A previously
      well HIV negative 17 year old boy presented to Mseleni hospital in December 2011
      with a short history of worsening shortness of breath on exertion. The history
      had been preceded by a brief upper respiratory tract infection with general
      malaise and headache, from which he had recovered fully. On examination, he was
      clammy, peripherally shut down and clearly in respiratory distress. He had a
      raised jugular venous pressure (JVP) and palpable displaced apex beat. He had a
      loud P2, third heart sound and pansystolic murmur over the apex. He had scattered
      inspiratory crepitations bibasally. Routine blood tests on admission, including
      malaria and viral serology, were unremarkable. A chest x-ray showed a grossly
      dilated cardiac shadow and enlarged pulmonary trunk. A cardiac ultrasound ruled
      out pericardial effusion but did show a dilated and hypokinetic left ventricle.
      He was diagnosed with dilated cardiomyopathy secondary to a viral infection and
      managed accordingly. LESSONS LEARNED: Dilated cardiomyopathy, although rare
      worldwide, is a significant problem throughout Africa. It has been shown to
      account for up to 48% of admissions with heart failure. Its aetiology is
      multifactorial and includes exposure to toxins and infectious agents. Presenting
      symptoms can be vague but improved prognosis and outcomes require prompt
      diagnosis and appropriate management.

PMID- 23121128
TI  - The effect of auditory cortex deactivation on stimulus-specific adaptation in the
      inferior colliculus of the rat.
AB  - Many neurons in the central auditory pathway, from the inferior colliculus (IC)
      to the auditory cortex (AC), respond less strongly to a commonly occurring
      stimulus than one that rarely occurs. The origin of this phenomenon, called
      stimulus-specific adaptation (SSA), remains uncertain. The AC sends descending
      projections to the IC that terminate most densely upon the dorsal, lateral and
      rostral IC cortices - areas where strong SSA has been reported. To investigate
      whether SSA in the IC is dependent upon the AC for its generation, we recorded
      the response from single IC neurons to stimuli presented in an oddball paradigm
      before, during and after reversibly deactivating the ipsilateral AC with a
      cryoloop. While changes in the basic response properties of the IC neurons were
      widespread (89%), changes in SSA sensitivity were less common; approximately half
      of the neurons recorded showed a significant change in SSA, while the other half
      remained unchanged. Changes in SSA could be in either direction: 18% enhanced
      their SSA sensitivity, while 34% showed reduced SSA sensitivity. For the majority
      of this latter group, cortical deactivation reduced, but did not eliminate,
      significant SSA levels. Only eight neurons seemed to inherit SSA from the AC, as
      their pre-existing significant level of SSA became non-significant during
      cortical deactivation. Thus, the presence of SSA in the IC is generally not
      dependent upon the corticocollicular projection, suggesting the AC is not
      essential for the generation of subcortical SSA; however, the AC may play a role
      in the modulation of subcortical SSA.

PMID- 23121129
TI  - Disproportionation channel of self-reaction of hydroxyl radical, OH + OH -> H2O +
      O, studied by time-resolved oxygen atom trapping.
AB  - The disproportionation channel of the self-reaction of hydroxyl radicals, OH + OH
      -> H(2)O + O (1a) was studied using pulsed laser photolysis coupled to transient
      UV-vis absorption spectroscopy over the 298-414 K temperature and 3-10 bar
      pressure ranges (bath gas He). To distinguish channel 1a from the recombination
      channel 1b, OH + OH -> H(2)O(2) (1b), time-resolved trapping of oxygen atoms,
      produced in channel 1a, was used. The ozone produced in the reaction of oxygen
      atoms with molecular oxygen was measured using strong UV absorption at 253.7 nm.
      The results of this study (k(1a) = (1.38 +/- 0.20) * 10(-12) (T/300)(-0.76)
      confirm the IUPAC recommended value of Bedjanian et al. (J. Phys. Chem. A1999,
      103, 7017-7025), as well as the negative temperature dependence over the
      temperature range studied, and do not confirm the ca. 1.8 higher value obtained
      in the most recent study of Bahng et al. (J. Phys. Chem. A2007, 111, 3850-3861).
      The V-shaped temperature dependence of k(1a) based on combined current and
      previous studies in the temperature range of 233-2380 K is k(1a) = (5.1 exp(
      T/190 K) + 0.30(T/300 K)(1.73)) * 10(-12) cm(3) molecule(-1) s(-1).

PMID- 23121130
TI  - Dedicated emergency theatres improve service delivery and surgeons' job
      satisfaction.
AB  - BACKGROUND: There are well-described benefits to separating emergency and
      elective surgery. Geelong Hospital lacked the resources to implement a separate
      acute surgical unit, but instituted daily dedicated emergency general surgery
      operating sessions, managed by an on-site consultant. This study aims to assess
      the impact of this on service delivery and surgeons' job satisfaction. METHODS:
      From 1 February 2011, daily half-day operating lists were allocated for general
      surgical emergencies. Patients treated on these lists were studied prospectively
      until 31 December 2011. Theatre waiting times and hospital stay were compared
      with the previous year. A quality-of-life questionnaire was administered to
      participating surgeons before the project commenced and after 6 months. RESULTS:
      A total of 966 patients underwent surgery during an emergency general surgery
      admission in the control period, and 984 underwent surgery during the study
      period. The median time from arrival in the emergency department (ED) to surgery
      was reduced from 19 (18-21) h in the control group to 18 (17-19) h in the study
      group (P = 0.033). The time from booking surgery to operation was reduced from
      4.8 (4.3-5.4) h to 3.9 (3.5-4.3) h (P < 0.0001). For patients undergoing
      emergency laparotomy, the time from booking to surgery was reduced from 3.1 (2.2
      4.1) to 2.4 (1.8-2.9) h, and hospital stay was reduced from 13 (11-15) to 10 (9
      12) days (P = 0.0089). The surgeons' responses to the questionnaires showed
      improvement in job satisfaction (P < 0.0001). CONCLUSION: This intervention has
      improved service delivery for emergency surgery patients, and improved the
      participating surgeons' job satisfaction.

PMID- 23121131
TI  - Cause-specific mortality in a Chinese chrysotile textile worker cohort.
AB  - Chrysotile asbestos has continued to be mined and used in China, but its health
      effects on exposed workers have not been well documented. This study was
      conducted to give a complete picture about cause-specific mortality in Chinese
      asbestos workers. A cohort of 586 males and 279 females from a chrysotile textile
      factory were prospectively followed for 37 years. Their vital status was
      identified, and the date and underlying cause of death were verified from death
      registry. Cause-specific standardized mortality ratios by gender were computed
      with nationwide gender- and cause-specific mortality rates as reference. Male
      workers were 11 years older, and had 6 years longer exposure duration than
      females; 79% in males and 1% in females smoked. In males, the mortality rate of
      all cancers doubled; both larynx and lung cancer were four-fold, and mesothelioma
      was 33-fold. In females, there was slightly excess mortality from lung cancer and
      all cancers, and significant increase in mesothelioma and ovarian cancer. Other
      significantly increased mortality was seen from cancers of thymus, small
      intestine and penis in males, and cancers of bone and bladder in females. In
      addition to asbestosis, mortality from pulmonary heart disease was significantly
      elevated in both genders. The data confirmed significantly excess mortality from
      mesothelioma in either gender, lung and larynx cancers in males, and ovarian
      cancer in females. A gender difference in mortality from lung cancer and all
      cancers could be mainly due to the discrepancies in age, exposure duration and
      smoking between the male and female workers.

PMID- 23121133
TI  - Brain magnetic resonance imaging and motor and intellectual functioning in 86
      patients born at term with spastic diplegia.
AB  - AIM: To investigate the association between magnetic resonance imaging (MRI)
      patterns and motor function, epileptic episodes, and IQ or developmental quotient
      in patients born at term with spastic diplegia. METHOD: Eighty-six patients born
      at term with cerebral palsy (CP) and spastic diplegia (54 males, 32 females;
      median age 20 y, range 7-42 y) among 829 patients with CP underwent brain MRI
      between 1990 and 2008. The MRI and clinical findings were analysed
      retrospectively. Intellectual disability was classified according to the Enjoji
      developmental test or the Wechsler Intelligence Scale for Children (3rd edition).
      RESULTS: The median ages at diagnosis of CP, assignment of Gross Motor Function
      Classification System (GMFCS) level, cognitive assessment, and MRI were 2 years
      (range 5 mo-8 y), 6 years (2 y 8 mo-19 y), 6 years (1 y 4 mo-19 y), and 7 years
      (10 mo-30 y) respectively. MRI included normal findings (41.9%), periventricular
      leukomalacia, hypomyelination, and porencephaly/periventricular venous
      infarction. The frequency of patients in GMFCS levels III to V and intellectual
      disability did not differ between those with normal and abnormal MRI findings.
      Patients with normal MRI findings had significantly fewer epileptic episodes than
      those with abnormal ones (p=0.001). INTERPRETATION: Varied MRI findings, as well
      as the presence of severe motor dysfunction and intellectual disability (despite
      normal MRI), suggest that patients born at term with spastic diplegia had
      heterogeneous and unidentified pathophysiology.

PMID- 23121132
TI  - Quantitative analysis of pheromone-binding protein specificity.
AB  - Many pheromones have very low water solubility, posing experimental difficulties
      for quantitative binding measurements. A new method is presented for determining
      thermodynamically valid dissociation constants for ligands binding to pheromone
      binding proteins, using beta-cyclodextrin as a solubilizer and transfer agent.
      The method is applied to LUSH, a Drosophila odorant-binding protein that binds
      the pheromone 11-cis vaccenyl acetate (cVA). Refolding of LUSH expressed in
      Escherichia coli was assessed by measuring N-phenyl-1-naphthylamine (NPN) binding
      and Forster resonance energy transfer between LUSH tryptophan 123 (W123) and NPN.
      Binding of cVA was measured from quenching of W123 fluorescence as a function of
      cVA concentration. The equilibrium constant for transfer of cVA between beta
      cyclodextrin and LUSH was determined from a linked equilibria model. This
      constant, multiplied by the beta-cyclodextrin-cVA dissociation constant, gives
      the LUSH-cVA dissociation constant: ~100 nM. It was also found that other ligands
      quench W123 fluorescence. The LUSH-ligand dissociation constants were determined
      to be ~200 nM for the silk moth pheromone bombykol and ~90 nM for methyl oleate.
      The results indicate that the ligand-binding cavity of LUSH can accommodate a
      variety ligands with strong binding interactions. Implications of this for the
      Laughlin, Ha, Jones and Smith model of pheromone reception are discussed.

PMID- 23121134
TI  - Analysis of Ah receptor binding affinities of polybrominated diphenyl ethers via
      in silico molecular docking and 3D-QSAR.
AB  - Polybrominated diphenyl ethers (PBDEs) have become ubiquitous contaminations due
      to their use as flame retardants. The structural similarity of PBDE to some
      dioxin-like compounds suggested that they may share similar toxicological
      effects: they might activate the aryl hydrocarbon receptor (AhR) signal
      transduction pathway and thus might have adverse effects on wildlife and humans.
      In this study, in silico computational workflow combining molecular docking and
      three-dimensional quantitative structure-activity relationship (3D-QSAR) was
      performed to investigate the binding interactions between PBDEs and AhR and the
      structural features affecting the AhR binding affinity of PBDE. The molecular
      docking showed that hydrogen-bond and hydrophobic interactions were the major
      driving forces for the binding of ligands to AhR, and several key amino acid
      residues were also identified. The CoMSIA model was developed from the
      conformations obtained from molecular docking and exhibited satisfactory results
      as q (2) of 0.605 and r (2) of 0.996. Furthermore, the derived model had good
      robustness and statistical significance in both internal and external
      validations. The 3D contour maps generated from CoMSIA provided important
      structural features influence the binding affinity. The obtained results were
      beneficial to better understand the toxicological mechanism of PBDEs.

PMID- 23121135
TI  - Luminal uptake of Vibrio (Listonella) anguillarum by shed enterocytes--a novel
      early defence strategy in larval fish.
AB  - As adhesion and translocation through fish gut enterocytes of the pathogen Vibrio
      (Listonella) anguillarum are not well investigated, the effective cause of
      disease and mortality outbreaks in larval sea bass, Dicentrarchus labrax,
      suffering from vibriosis is unknown. We detected V. anguillarum within the gut of
      experimentally infected gnotobiotic sea bass larvae using transmission electron
      microscopy and immunogold labelling. Intact bacteria were observed in close
      contact with the apical brush border in the gut lumen. Enterocytes contained
      lysosomes positive for protein A-gold particles suggesting intracellular
      elimination of bacterial fragments. Shed intestinal cells were regularly
      visualized in the gut lumen in late stages of exposure. Some of the luminal cells
      showed invagination and putative engulfment of bacterial structures by pseudopod
      like formations. The engulfed structures were positive for protein A-colloidal
      gold indicating that these structures were V. anguillarum. Immunogold positive
      thread-like structures secreted by V. anguillarum suggested the presence of outer
      membrane vesicles (MVs) hypothesizing that MVs are potent transporters of active
      virulence factors to sea bass gut cells suggestive for a substantial role in
      biofilm formation and pathogenesis. We put forward the hypothesis that MVs are
      important in the pathogenesis of V. anguillarum in sea bass larvae.

PMID- 23121136
TI  - Do baseline diastolic echocardiographic parameters predict outcome after
      resynchronization therapy? Results from the PROSPECT trial.
AB  - INTRODUCTION: Cardiac resynchronization therapy (CRT) can improve clinical and
      cardiac structural status in heart failure patients. The role of baseline
      diastolic echocardiographic parameters to characterize the likelihood of positive
      outcomes is not well known. We explored relationships between diastolic
      parameters and outcomes 6 months after CRT implant in the Predictors of Response
      to CRT (PROSPECT) Trial. HYPOTHESIS: We hypothesized that diastolic
      echocardiographic parameters were associated with clinical and structural
      outcomes in CRT patients. METHODS: For 426 patients in PROSPECT, a prospective
      observational trial of CRT, baseline E/A ratio, left atrial (LA) area, isovolumic
      relaxation time, left ventricular inflow deceleration time, E' velocity, and E/E'
      ratio were evaluated and related to 6-month clinical composite score (CCS) and
      left ventricular end-systolic volume (LVESV) reduction using Spearman rank-order
      correlations. Parameters associated with outcomes were analyzed further by
      discrete categorization. RESULTS: As continuous variables, only E/A ratio and LA
      area correlated with CCSs (P = 0.017, P = 0.045, respectively) and relative
      change in LVESV at 6 months (P < 0.0001, P = 0.001, respectively). As discrete
      variables, E/A ratio and LA area also correlated with CCSs and LVESV. CONCLUSION:
      Diastolic echo parameters E/A ratio and LA area were associated with clinical and
      structural outcomes in CRT patients at 6 months.

PMID- 23121121
TI  - Metal-organic frameworks and self-assembled supramolecular coordination
      complexes: comparing and contrasting the design, synthesis, and functionality of
      metal-organic materials.

PMID- 23121138
TI  - JCAPN editor transition: a new era begins.

PMID- 23121140
TI  - Habit reversal training for children with tourette syndrome: update and review.
AB  - TOPIC: Habit reversal training (HRT) is emerging as an efficacious behavioral
      intervention for Tourette syndrome in children and adults. PURPOSE: The purpose
      of this article is to review the recent literature investigating the efficacy of
      HRT for treating children with chronic tic disorders. SOURCES: This review
      examines single-subject design studies and randomized, controlled trials of HRT
      conducted in children with chronic tic disorders since 2000. CONCLUSIONS:
      Intervention built on HRT appears to be effective for decreasing tic severity in
      children and adolescents. Results from a recent multisite trial suggest that
      incorporation of functional analysis may enhance the effectiveness of traditional
      HRT.

PMID- 23121139
TI  - Childhood predictors of adolescent competence and self-worth in rural youth.
AB  - PROBLEM: Urban children who become competent adults despite circumstances that
      place their development and mental health at risk are considered to be resilient.
      Less is known about the risk and protective factors that characterize resilience
      among Hispanic/Latinos living in rural areas. METHODS: Data for regression
      analyses were collected when children (n = 603; 54% Hispanic/Latino) enrolled in
      the study in fifth grade (M = 10.4 years of age), and again 5 years later when
      they were in high school (M = 15 years of age). FINDINGS: Statistically
      significant predictors of competence and self-worth in high schoolers included
      gender, ethnicity, and mother's education, as well as stress, temperament (task
      persistence), and competences measured in grade school. CONCLUSIONS: Parents'
      perception of child's temperament is a significant predictor of future competence
      and self-worth among rural adolescents.

PMID- 23121141
TI  - Adolescent depression: meeting therapeutic challenges through an integrated
      narrative approach.
AB  - TOPIC: The adolescent period is a time of transition and change often associated
      with losses and adjustment issues at the family, school, and individual levels.
      When this normal developmental transition is interrupted and compounded by
      depressive illness, treatment needs and nursing therapeutic challenges can be
      daunting. PURPOSE: This clinically based article explores the clinical process
      and progress in work with a 14-year-old adolescent boy who was diagnosed with a
      major depressive episode. Core clinical features, distinguishing characteristics
      of depression in youth, as well as specific therapeutic issues and challenges are
      discussed. The value of an integrated clinical approach with special emphasis on
      narrative methods both for achievement of clinical goals and for establishing a
      therapeutic alliance is highlighted. SOURCES USED: The study used published
      literature and the author's professional and clinical experiences. CONCLUSION:
      Nursing therapeutics with adolescents experiencing depression must embrace a
      holistic integrated approach to adolescent recovery with an emphasis on what
      works with each unique clinical situation. Special attention to the nurse
      adolescent therapeutic alliance not only facilitates achievement of therapeutic
      goals related to the depressive illness, but in addition, supports the shaping of
      a new self-narrative, wholeness, and healthy adolescent development and well
      being.

PMID- 23121142
TI  - Testing a model of depression among Thai adolescents.
AB  - PROBLEM: This predictive correlational study was designed to test a comprehensive
      model of depression for Thai adolescents. METHODS: This sample included 800 high
      school students in Chiang Mai, Thailand. Data were collected using self-reported
      measures of depression, negative automatic thoughts, effective social problem
      solving, ineffective social problem solving, rumination, parental care, parental
      overprotection, and negative life events. FINDINGS: Structural equation modeling
      revealed that negative automatic thoughts, effective and ineffective social
      problem solving mediated the effects of rumination, negative life events, and
      parental care and overprotection on adolescent depression. CONCLUSION: These
      findings provide new knowledge about identified factors and the mechanisms of
      their influence on depression among Thai adolescents, which are appropriate for
      targeting preventive interventions.

PMID- 23121137
TI  - Understanding the rhythm of breathing: so near, yet so far.
AB  - Breathing is an essential behavior that presents a unique opportunity to
      understand how the nervous system functions normally, how it balances inherent
      robustness with a highly regulated lability, how it adapts to both rapidly and
      slowly changing conditions, and how particular dysfunctions result in disease. We
      focus on recent advancements related to two essential sites for respiratory
      rhythmogenesis: (a) the preBotzinger Complex (preBotC) as the site for the
      generation of inspiratory rhythm and (b) the retrotrapezoid nucleus/parafacial
      respiratory group (RTN/pFRG) as the site for the generation of active expiration.

PMID- 23121143
TI  - A quality improvement project to decrease the length of stay on a psychiatric
      adolescent partial hospital program.
AB  - PROBLEM: Clinicians are challenged to treat adolescents with life-threatening
      behaviors while accessing fewer mental health resources with increased
      utilization management pressures. METHODS: Dialectical behavior therapy (DBT)
      skills training groups were implemented as a quality improvement project to
      decrease the length of stay on an adolescent psychiatric partial hospital program
      by reducing potential life-threatening behaviors. FINDINGS: The average length of
      stay decreased nearly 5 days during the project. Potential life-threatening urges
      seemed to increase from pretreatment findings while life-threatening actions
      appeared to decrease. CONCLUSIONS: While the findings were inconclusive regarding
      the actual effect on life-threatening urges and behaviors, dialectical behavior
      therapy skills training groups may have positive outcomes on an adolescent
      psychiatric partial hospital program.

PMID- 23121144
TI  - Underaged patients' opinions toward different containment measures: a
      questionnaire survey in Finnish adolescent psychiatry.
AB  - PROBLEM: The current literature does not provide an understanding of adolescent
      patients' opinions toward various containment measures and how these are related
      to the opinions of the staff who are caring for them. METHODS: The study
      population comprised 81 inpatients and 128 staff members in an inpatient setting
      in Finland. Their opinions were studied using the Attitude to Containment
      Measures Questionnaire. FINDINGS: The adolescents were more critical toward most
      containment measures compared to the staff. Exactly as reported in previous
      studies among adult service users, the containment measures most accepted by the
      adolescents were as-needed medication, intermittent observation, and time out.
      They were considered as helpful, safe, and respectful methods. Net bed, which has
      never been used in Finland, was most disapproved. It was considered as a
      distressing, inhuman, and cruel method. Opinions toward mechanical restraint,
      which is commonly used in Finnish adolescent psychiatry, were noticeable:
      adolescents rated mechanical restraint among the three least accepted, staff
      among the three most accepted containment methods. Adolescents considered it as
      distressing and not consistent of human dignity. CONCLUSIONS: Adolescents
      disapprove of containment measures some of which are widely used in psychiatric
      practice. Their opinions differ significantly from those of the staff. New ways
      to manage crisis situations should be developed. Where containment cannot be
      avoided, information, explanation about the procedures involved, and debriefing
      should be offered to an underaged patient in a manner which takes account of
      his/her developmental level.

PMID- 23121145
TI  - A pilot program to address healthy sexual behaviors among girls in juvenile
      detention.
AB  - PURPOSE: This pilot study was designed to determine the effectiveness of an
      intervention on sexual behavior among girls in juvenile detention. METHODS: The
      pre/posttest model assessed for changes in knowledge, attitudes, and reported
      behaviors. This program merged three curricula to create the unique Young Women
      Get Real Program with nursing student program facilitators. FINDINGS: Despite
      high levels of satisfaction with the program, the data related to the final
      sample (n = 35) failed to reveal significant changes in measured variables.
      CONCLUSIONS: The results may inform nurses as they pursue interventions to
      promote responsible sexual behavior in selected populations.

PMID- 23121146
TI  - Psychopharmacology column: the use of lithium carbonate with pediatric
      populations.

PMID- 23121147
TI  - Gender dysphoria in children: let's think this through.

PMID- 23121148
TI  - Incidence of second primary malignancies in patients with treated head and neck
      cancer: a comprehensive review of literature.
AB  - BACKGROUND: Increased incidence of a second primary aero-digestive malignancy
      after an index head and neck cancer (HNC) is well-documented. Furthermore, a
      clear set of surveillance strategies for second primary aero-digestive cancers in
      these patients exists. METHODS: The goal of this article is to review the
      published literature on risk of second primary malignancies (SPMs) (including
      aero-digestive malignancies) after a treated index HNC as well as its associated
      predictors, prognosis and surveillance. Most relevant publications were
      identified through searching the PubMed database for articles published up to
      July 2012; epidemiologic evidence was synthesized and thoroughly analyzed.
      FINDINGS: Data from randomized controlled trials, meta-analyses, population-based
      and cohort group studies, prior reviews, and case reports indicate an increased
      incidence of various SPMs after occurrence of a HNC. These cancers are not
      limited to upper aero-digestive sites. Common risk factors including
      environmental, genetic and immune factors may explain the increased incidence of
      second cancers in this patient population. In addition, site of the index HNC may
      predict the site of a future SPM. CONCLUSIONS: As a general rule, oral cavity and
      oropharyngeal squamous cell cancers are associated more with head and neck region
      SPM, while laryngeal and hypopharyngeal cancers - with that of the lung. As these
      cancers confer dismal prognosis and shorter survival in patients with HNCs,
      several literature sources recommend close surveillance for and an aggressive
      therapy of SPM. Notwithstanding, their optimal management and follow-up schedule
      remains to be established.

PMID- 23121149
TI  - Gabapentin enacarbil in Japanese patients with restless legs syndrome: a 12-week,
      randomized, double-blind, placebo-controlled, parallel-group study.
AB  - OBJECTIVE: Gabapentin enacarbil (GEn) was effective and well-tolerated for the
      treatment of restless legs syndrome (RLS) in North American studies. However, no
      placebo-controlled studies of GEn have been performed in Asian patients with RLS.
      Therefore, we investigated the efficacy and safety of GEn in Japanese patients
      with RLS to determine the optimal dosage. RESEARCH DESIGN AND METHODS:
      Outpatients with RLS (International Restless Legs Syndrome Rating Scale (IRLS)
      scores >=15) were randomized (n = 474) and treated (n = 469) in a double-blind
      manner with once-daily placebo (n = 116), 600 (n = 120), 900 (n = 119) or 1200 (n
      = 114) mg GEn for 12 weeks. CLINICAL TRIAL REGISTRATION: NCT00530530
      (ClinicalTrials.gov) MAIN OUTCOME MEASURE: The primary outcome was the change in
      IRLS score. Secondary outcomes included Investigator (ICGI)- and Patient (PCGI)
      rated Clinical Global Impression and adverse events. RESULTS: The mean change in
      IRLS score from baseline to the final observation was -8.96 for placebo versus 
      11.10, -10.28 and -11.38 for 600, 900 and 1200 mg GEn. Williams' multiple
      comparison test showed that only 1200 mg GEn was superior to placebo (p = 0.011).
      However, in post hoc mixed-effects models with repeated measures, which accounted
      for the time-course of changes in IRLS, the placebo-adjusted changes were -2.31, 
      1.92 and -2.31 for 600, 900 and 1200 mg GEn. ICGI and PCGI response rates were
      significantly greater for all three GEn doses versus placebo (all p <= 0.014).
      Adverse events, including somnolence, dizziness and nasopharyngitis, were
      frequent but of mild-to-moderate severity. However, there was a tendency toward a
      dose-dependent increase in the incidence of adverse events. CONCLUSIONS: GEn is
      effective and well-tolerated for the treatment of RLS in Japanese patients. All
      three doses produced improvements in IRLS compared with placebo; 600 mg GEn is a
      suitable target dose. However, our analysis possibly introduced positive bias by
      assuming that symptoms improve after discontinuation.

PMID- 23121150
TI  - Efficacy and safety of ribavirin plus pegylated interferon alfa in geriatric
      patients with chronic hepatitis C.
AB  - BACKGROUND: Limited data are available on the efficacy and safety of antiviral
      therapy in geriatric patients with chronic hepatitis C virus (HCV) infection.
      AIM: To evaluate the efficacy and safety of pegylated interferon (pegIFN) plus
      ribavirin (RBV) therapy in geriatric HCV-infected patients. METHODS: Ninety-one
      geriatric patients (age >=65 years; the elderly group) with HCV infection and 91
      gender- and HCV genotype-matched middle-aged patients (age 50-64 years; the
      younger group) were assigned to receive weekly pegIFN injection plus weight-based
      oral RBV for 24 weeks. The on- and off-treatment virological responses were
      evaluated for treatment efficacy. RESULTS: In intention-to-treat analysis, the
      sustained virological response (SVR) rate was substantially decreased in the
      elderly patients (elderly group vs. younger group, 40.7% vs. 61.5%, respectively;
      P = 0.005). The SVR rate was significantly lower in geriatric patients than in
      middle-aged patients with HCV genotype non-1 (54.3% vs. 82.9%; P = 0.01), but the
      difference was not significant with HCV genotype 1 (32.1% vs. 48.2%; P = 0.083).
      Furthermore, the older patients infected with HCV genotype non-1 who achieved a
      rapid virological response had a similar SVR rate to that of the younger
      patients. The withdrawal rate was 13.2% in the elderly group and 7.7% in the
      younger group. CONCLUSIONS: Compared with middle-aged patients, the therapeutic
      efficacy of pegylated interferon plus ribavirin therapy is lower in hepatitis C
      virus-infected geriatric patients with an acceptable withdrawal rate. Considering
      prolonged lifespan in geriatric patients, we recommend treating geriatric
      hepatitis C virus-infected patients who have significant hepatic fibrosis and no
      other health problems.

PMID- 23121151
TI  - Composition and properties of complexes between spherical polycationic brushes
      and anionic liposomes.
AB  - A spherical polycationic brush (SPB) is made by graft-polymerizing a cationic
      monomer onto the surface of a 100 nm polystyrene bead. It is possible to adsorb
      anionic liposomes (40-60 nm diameter) onto the SPBs while maintaining the
      liposome integrity. The liposomes were constructed with phosphatidyl choline (PC)
      admixed with 0.05-0.4 mol fraction of an dianionic lipid, cardiolipin (CL(2-)).
      As shown by electrophoretic mobility measurements, SPB-to-liposome complexation
      leads to a conversion from the initial positive charge of the copolymer to a
      negative charge. The higher the CL(2-) content of the liposomes, the lower the
      concentration needed for charge neutralization. Dynamic light scattering (DLS)
      revealed that multicomplex aggregates are formed with a maximum size at the
      SPB/liposome charge-equivalence point. Experiments with fluorescent-labeled
      liposomes show that at low CL(2-) content about 80 liposomes are adsorbed per
      SPB. As the mole fraction of CL(2-) increases from 0.05 to 0.4, fewer liposomes
      adsorb owing to electrostatic repulsion among neighboring liposomes. The effect
      of added NaCl also depends upon the CL(2-) content. With 0.05 mol fraction CL(2
      ), the SPB/liposome complex dissociates into its components at 0.15 M NaCl. With
      a mole fraction of >0.1, complexes fail to dissociate even at 1.2 M NaCl.
      Additional information about the SPB/liposome morphology was obtained from cryo
      TEM. For example, cryo-TEM data confirm liposome integrity upon complexation, a
      behavior that contrasts with the liposome destruction as found with adsorption to
      many other types of surfaces.

PMID- 23121152
TI  - The impact of oral health literacy on periodontal health status.
AB  - OBJECTIVE: The objective of this study was to describe oral health literacy (OHL)
      among periodontal patients and to examine its association with periodontal health
      status. METHODS: This cross-sectional study included new and referred patients
      presenting to the University of North Carolina Graduate Periodontology Clinic.
      Sociodemographic and dental history information were collected. OHL was measured
      using a dental word recognition instrument, Rapid Estimate of Adult Literacy-30
      (REALD-30). Clinical periodontal examinations were completed. RESULTS: One
      hundred and twenty-eight participants enrolled and 121 completed all study
      examinations and instruments. Despite a high level of education among
      participants in our study, low levels of OHL were found in one-third (33 percent)
      of the study population. Thirty-one percent had moderate OHL (score of 22-25), 37
      percent had high OHL (score >= 26). The mean REALD-30 score was 23. Fifty-three
      percent of participants had severe periodontitis, 29 percent had moderate
      periodontitis, and 18 percent had mild or no periodontitis. Bivariate analysis
      showed a significant association between OHL and periodontal status (P < 0.05).
      The effect of OHL on periodontal health status remained statistically significant
      (P < 0.002) even after controlling for smoking, race, and dental insurance.
      CONCLUSION: Lower OHL was associated with more severe periodontal disease among
      new and referred patients presenting to the University of North Carolina Graduate
      Periodontology Clinics.

PMID- 23121153
TI  - Cold ischemic time is critical in outcomes of expanded criteria donor renal
      transplantation.
AB  - The outcomes of expanded criteria donor (ECD) kidneys have been reported to be
      inferior compared with standard criteria donor (SCD) kidneys. However, the graft
      survival rate of ECD is not so inferior to SCD in Korea. The purposes of this
      study were to compare the outcomes of ECD kidneys with SCD kidneys and identify
      the influencing factors. We retrospectively studied 143 deceased donor
      transplants from August 2006 to June 2010. The patients were divided into SCD (n
      = 117) and ECD (n = 26) by UNOS criteria. The one- and three-yr graft survival
      rates of SCD and ECD (99.1% and 94.4% vs. 100% and 92.9%, respectively, p = 0.15)
      were not significantly different between groups. The mean cold ischemic time
      (CIT) was 3.8 +/- 2.2 h. When compared the outcome of ECD kidneys with data
      reported by Organ Procurement and Transplantation Network and the Scientific
      Registry of Transplant Recipients (OPTN/SRTR) (one- and three-yr graft survival
      rate: 86.7% and 73.2%), the graft survival rate of our center was superior. In
      OPTN/SRTR data, transplant with CIT shorter than 11 h was only 20%. The outcomes
      of ECD grafts are outstanding and comparable with SCD grafts in our center, and
      the only distinguishing factor is markedly short CIT. Finishing the allocation
      before organ recovery and immediate operations after recovery could shorten the
      CIT.

PMID- 23121154
TI  - Bruxism and associated factors among Dutch adolescents.
AB  - OBJECTIVES: To assess the prevalence rates of self-reported sleep bruxism and
      awake bruxism and their associations with several demographical, exogenous, and
      psychosocial factors among Dutch adolescents. METHODS: In a cross-sectional
      questionnaire survey, 4285 questionnaires were completed, with an about equal
      gender distribution and with ages ranging from 10 to 22 years. RESULTS: In the
      group of 4235 12- to 18-year-old adolescents, sleep bruxism had a reported
      prevalence of 14.8% and awake bruxism of 8.7%. Logistic regression analyses
      revealed that sleep bruxism was associated with female gender [OR = 1.49 (95% CI
      = 1.23-1.81)], pain or tense feeling in the jaws upon awakening in the morning
      [OR = 1.47 (95% CI = 1.17-1.86)], clicking joint sounds [OR = 1.31 (95% CI = 1.03
      1.65)], stress [OR = 1.25 (95% CI = 1.00-1.55)], and depressive mood [OR = 1.35
      (95% CI = 1.10-1.65)]. Awake bruxism was associated with orofacial pain [OR =
      1.49 (95% CI = 1.16-1.91)], clicking joint sounds [OR = 1.50 (95% CI = 1.13
      1.98)], scraping joint sounds [OR = 2.03 (95% CI = 1.21-3.37)], stress [OR = 1.36
      (95% CI = 1.03-1.78)], depressive mood [OR = 1.82 (95% CI = 1.42-2.35)], and
      smoking [OR = 1.42 (95% CI = 1.06-1.89)]. CONCLUSIONS: Sleep bruxism and awake
      bruxism are common conditions among Dutch adolescents, with self-reported
      prevalence rates that are slightly higher than those derived from most large
      scale studies on adults. Several predictor variables were found to be exclusively
      associated with either form of bruxism, corroborating the common suggestion that
      both circadian manifestations are, at least in part, different entities.

PMID- 23121155
TI  - The substrate specificity of mitochondrial carriers: mutagenesis revisited.
AB  - Mitochondrial carriers transport inorganic ions, nucleotides, amino acids, keto
      acids and cofactors across the mitochondrial inner membrane. Structurally they
      consist of three domains, each containing two transmembrane alpha-helices linked
      by a short alpha-helix and loop. The substrate binds to three major contact
      points in the central cavity. The class of substrate (e.g., adenine nucleotides)
      is determined by contact point II on transmembrane alpha-helix H4 and the type of
      substrate within the class (e.g., ADP, coenzyme A) by contact point I in H2,
      whereas contact point III on H6 is most usually a positively charged residue,
      irrespective of the type or class. Two salt bridge networks, consisting of
      conserved and symmetric residues, are located on the matrix and cytoplasmic side
      of the cavity. These residues are part of the gates that are involved in opening
      and closing of the carrier during the transport cycle, exposing the central
      substrate binding site to either side of the membrane in an alternating way. Here
      we revisit the plethora of mutagenesis data that have been collected over the
      last two decades to see if the residues in the proposed binding site and salt
      bridge networks are indeed important for function. The analysis shows that the
      major contact points of the substrate binding site are indeed crucial for
      function and in defining the specificity. The matrix salt bridge network is more
      critical for function than the cytoplasmic salt bridge network in agreement with
      its central position, but neither is likely to be involved in substrate
      recognition directly.

PMID- 23121156
TI  - Portrayals of teen smoking, drinking, and drug use in recent popular movies.
AB  - Studies indicate that films can influence adolescents' attitudes toward and
      initiation of substance use. It is therefore important to periodically assess
      film content to assess the types of imagery adolescents are likely to encounter.
      This study content analyzed teen characters in top films featuring teenagers from
      2007, 2008, and 2009 to assess smoking, drinking, and drug use portrayals.
      Results indicate a relatively low incidence of smoking and drug use. However, one
      in five teen characters are shown drinking. Overall, substance use depictions
      have diminished considerably compared with films released at the earlier end of
      the decade. However, consequences of substance use were infrequently depicted,
      and characters seldom refused invitations to drink or do drugs. Given these
      findings, some potentially counterproductive outcomes are discussed.

PMID- 23121157
TI  - Neuronal responses to face-like stimuli in the monkey pulvinar.
AB  - The pulvinar nuclei appear to function as the subcortical visual pathway that
      bypasses the striate cortex, rapidly processing coarse facial information. We
      investigated responses from monkey pulvinar neurons during a delayed non-matching
      to-sample task, in which monkeys were required to discriminate 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 401 neurons recorded, 165 neurons responded
      differentially to the visual stimuli. These visual responses were suppressed by
      scrambling the images. Although these neurons exhibited a broad response latency
      distribution, face-like patterns elicited responses with the shortest latencies
      (approximately 50 ms). Multidimensional scaling analysis indicated that the
      pulvinar neurons could specifically encode face-like patterns during the first 50
      ms period after stimulus onset and classify the stimuli into one of the five
      different categories during the next 50-ms period. The amount of stimulus
      information conveyed by the pulvinar neurons and the number of stimulus
      differentiating neurons were consistently higher during the second 50-ms period
      than during the first 50-ms period. These results suggest that responsiveness to
      face-like patterns during the first 50-ms period might be attributed to ascending
      inputs from the superior colliculus or the retina, while responsiveness to the
      five different stimulus categories during the second 50-ms period might be
      mediated by descending inputs from cortical regions. These findings provide
      neurophysiological evidence for pulvinar involvement in social cognition and,
      specifically, rapid coarse facial information processing.

PMID- 23121158
TI  - Prevalence and risk factors for pelvic organ prolapse 20 years after childbirth:
      a national cohort study in singleton primiparae after vaginal or caesarean
      delivery.
AB  - OBJECTIVE: To investigate prevalence and risk factors for symptomatic pelvic
      organ prolapse (sPOP) and sPOP concomitant with urinary incontinence (UI) in
      women 20 years after one vaginal delivery or one caesarean delivery. DESIGN:
      Registry-based national cohort study. SETTING: Women who returned a postal
      questionnaire in 2008 (response rate 65.2%). POPULATION: Singleton primiparae
      with a birth in 1985-88 and no further births (n = 5236). METHODS: The SWEPOP
      study used validated questionnaires about sPOP and UI. MAIN OUTCOME MEASURES:
      Prevalence rate and risk of sPOP with or without concomitant UI. RESULTS:
      Prevalence of sPOP was higher after vaginal delivery compared with caesarean
      section (14.6 versus 6.3%, odds ratio [OR] 2.55; 95% confidence interval [95% CI]
      1.98-3.28) but was not increased after acute compared with elective caesarean
      section. Episiotomy, vacuum extraction and second-degree or more laceration were
      not associated with increased risk of sPOP compared with spontaneous vaginal
      delivery. Symptomatic POP increased 3% (OR 1.03; 95% CI 1.01-1.05) with each unit
      increase of current BMI and by 3% (OR 1.03; 95% CI 1.02-1.05) for each 100 g
      increase of infant birthweight. Mothers <= 160 cm who delivered a child with
      birthweight >= 4000 g had a doubled prevalence of sPOP compared with short
      mothers who delivered an infant weighing < 4000 g (24.2 versus 13.4%, OR 2.06;
      95% CI 1.19-3.55). Women with sPOP had UI and UI > 10 years more often than women
      without prolapse. CONCLUSION: The prevalence of sPOP was doubled after vaginal
      delivery compared with caesarean section, two decades after one birth. Infant
      birthweight and current BMI were risk factors for sPOP after vaginal delivery.

PMID- 23121159
TI  - Nourishing networks: an interprofessional learning model and its application to
      the Australian rural health workforce.
AB  - CONTEXT: Access to continuing professional development for rural health
      clinicians requires strategies to overcome barriers associated with finances,
      travel and a lack of resources. Approaches to providing professional development
      need to transcend conventional educational methods and consider interprofessional
      educational opportunities to meet the diverse needs of the rural health
      workforce. Rural clinicians often work in professional isolation and frequently
      work collaboratively with clinicians from a range of other health disciplines.
      Interprofessional learning and practice is therefore important in a rural areas
      as clinicians working in these settings are often more reliant on each other and
      require an understanding of other's roles to provide effective health care. In
      addition, specialist services are limited in rural areas, with health
      professionals increasingly required to perform extended roles at an advanced
      practice level. ISSUES: A model for interprofessional learning has been developed
      to attempt to address the barriers related to the delivery of interprofessional
      education in the rural health setting in Australia. This model demonstrates a
      flexible approach to interprofessional learning which meets different educational
      needs across a number of health disciplines, and is tailored to varying levels of
      expertise. It incorporates three learning approaches: traditional learning,
      flexible learning and advanced practice. Each of these components of the model
      are described and the Nourishing Networks program is provided as an example of
      the application of the model in a rural setting, utilising 'eating disorders' as
      the educational topic. LESSONS LEARNED: Interprofessional learning can be
      delivered effectively in a rural setting by utilising technology to help bridge
      the isolation experienced in rural practice. Challenges in delivering the
      interprofessional learning program included: engaging rural general
      practitioners, utilising technology and maintaining participant engagement. The
      use of technology is essential to access a broad group of rural clinicians
      however, there are limitations in its use that must be acknowledged. The pilot of
      the Stepped Interprofessional Rural Learning Model and its application to eating
      disorders has scope for use in delivering education for other health topics.

PMID- 23121160
TI  - A call for more transparent reporting of error rates: the quality of AFLP data in
      ecological and evolutionary research.
AB  - Despite much discussion of the importance of quantifying and reporting genotyping
      error in molecular studies, it is still not standard practice in the literature.
      This is particularly a concern for amplified fragment length polymorphism (AFLP)
      studies, where differences in laboratory, peak-calling and locus-selection
      protocols can generate data sets varying widely in genotyping error rate, the
      number of loci used and potentially estimates of genetic diversity or
      differentiation. In our experience, papers rarely provide adequate information on
      AFLP reproducibility, making meaningful comparisons among studies difficult. To
      quantify the extent of this problem, we reviewed the current molecular ecology
      literature (470 recent AFLP articles) to determine the proportion of studies that
      report an error rate and follow established guidelines for assessing error. Fifty
      four per cent of recent articles do not report any assessment of data set
      reproducibility. Of those studies that do claim to have assessed reproducibility,
      the majority (~90%) either do not report a specific error rate or do not provide
      sufficient details to allow the reader to judge whether error was assessed
      correctly. Even of the papers that do report an error rate and provide details,
      many (>=23%) do not follow recommended standards for quantifying error. These
      issues also exist for other marker types such as microsatellites, and next
      generation sequencing techniques, particularly those which use restriction
      enzymes for fragment generation. Therefore, we urge all researchers conducting
      genotyping studies to estimate and more transparently report genotyping error
      using existing guidelines and encourage journals to enforce stricter standards
      for the publication of genotyping studies.

PMID- 23121161
TI  - Metabolomics of hexachlorocyclohexane (HCH) transformation: ratio of LinA to LinB
      determines metabolic fate of HCH isomers.
AB  - Although the production and use of technical hexachlorocyclohexane (HCH) and
      lindane (the purified insecticidal isomer gamma-HCH) are prohibited in most
      countries, residual concentrations still constitute an immense environmental
      burden. Many studies describe the mineralization of gamma-HCH by bacterial
      strains under aerobic conditions. However, the metabolic fate of the other HCH
      isomers is not well known. In this study, we investigated the transformation of
      alpha-, beta-, gamma-, delta-, epsilon-HCH, and a heptachlorocyclohexane isomer
      in the presence of varying ratios of the two enzymes that initiate gamma-HCH
      degradation, a dehydrochlorinase (LinA) and a haloalkane dehalogenase (LinB).
      Each substrate yielded a unique metabolic profile that was strongly dependent on
      the enzyme ratio. Comparison of these results to those of in vivo experiments
      with different bacterial isolates showed that HCH transformation in the tested
      strains was highly optimized towards productive metabolism of gamma-HCH and that
      under these conditions other HCH-isomers were metabolized to mixtures of
      dehydrochlorinated and hydroxylated side-products. In view of these results,
      bioremediation efforts need very careful planning and toxicities of accumulating
      metabolites need to be evaluated.

PMID- 23121162
TI  - Role of HLA class II loci polymorphism in the manifestation of type 1 diabetes in
      a Bengali Indian patient population.
AB  - To assess the contribution of the HLA class II region for susceptibility to type
      1 diabetes mellitus (T1DM), we investigated the association of HLA class II
      alleles-DP, DQ, and DRB1. Here, we present an extensive molecular typing for HLA
      class II alleles and their haplotypes in a Bengali-speaking Indian population of
      T1DM patients (n=151) and controls (n=151) from West Bengal. HLA typing was done
      by DNA sequencing using a 3730 DNA Analyzer. The individual analysis of each gene
      gave the following alleles to be higher in cases than in controls, thus making
      them susceptible alleles-DPA1*020103, DPB1*020102, DQA1*050101, DQA1*0201, and
      DQB1*020101G. Similarly, the following alleles are protective alleles in our
      study-DPA1*010602, DPB1*040101, DQA1*010201, DQA1*0103, and DRB1*15. Our result
      confidently establishes that HLA-DP allelic, and its haplotypic, diversity
      contributes significantly to the risk for T1DM. The DQA1*0103 allele is a novel
      allele with a significant association with the protection from T1DM. Among the
      various haplotypes tested, the DQA1*0201:DQB1*020101G, DQA1*050101:DQB1*020101G,
      and DQA1*0201:DQB1*030101G were the most frequently found in T1DM patients. In
      India, very few investigations have been undertaken to study the impact of the
      genetic background on the risk to develop T1DM in its population, where the
      annual average incidence is 10.5/100,000/year. In conclusion, the present study
      highlights the genetic effect of HLA haplotypes that contributes to the
      susceptibility to T1DM.

PMID- 23121163
TI  - Glutathione S-transferase P1-1 as a target for mesothelioma treatment.
AB  - Malignant pleural mesothelioma is a poorly responsive tumor known to overexpress
      the phase II detoxification enzyme glutathione-S-transferase, which catalyzes the
      conjugation between glutathione and platinum(II)-containing drugs. Therefore, we
      evaluated the effect of the strong glutathione S-transferase inhibitor NBDHEX on
      human mesothelioma cell lines (MSTO-211H, MPP89, MM-B1 and Mero 48a) featuring
      the most common mesothelioma phenotypes: epithelioid and biphasic. Even though a
      different response to NBDHEX was observed, the molecule was very effective on all
      cell lines tested, triggering a sustained activation of both JNK and p38,
      followed by caspase activation and apoptosis. NBDHEX also caused severe oxidative
      stress in the MPP89 cells and, to a lesser extent, in the MMB1 cells, while it
      did not cause a significant redox imbalance in the other cell lines. The efficacy
      of the drug was found to be comparable or even higher than that of cisplatin.
      Moreover, it showed synergistic or additive effects when used in combination with
      cisplatin. In conclusion, NBDHEX was effective on mesothelioma cell lines, with
      IC(50) values in the low micromolar range (IC(50) between 1 and 4 MUM). These
      findings indicate that NBDHEX, alone or in combination with cisplatin, is a
      promising new strategy for treating this rare and aggressive malignancy.

PMID- 23121164
TI  - The association of cerebral palsy with birth asphyxia: a definitional quagmire.
AB  - AIM: The aim of this study was to investigate whether current literature provides
      a useful body of evidence reflecting the proportion of cerebral palsy (CP) that
      is attributable to birth asphyxia. METHOD: We identified 23 studies conducted
      between 1986 and 2010 that provided data on intrapartum risks of CP. RESULTS: The
      proportion of CP with birth asphyxia as a precursor (case exposure rate) varied
      from less than 3% to over 50% in the 23 studies reviewed. The studies were
      heterogeneous in many regards, including the definitions for birth asphyxia and
      the outcome of CP. INTERPRETATIONS: Current data do not support the belief,
      widely held in the medical and legal communities, that birth asphyxia can be
      recognized reliably and specifically, or that much of CP is due to birth
      asphyxia. The very high case exposure rates linking birth asphyxia to CP can
      probably be attributed to several factors: the fact that the clinical picture at
      birth cannot specifically identify birth asphyxia; the definition of CP employed;
      and confusion of proximal effects - results - with causes. Further research is
      needed.

PMID- 23121165
TI  - Laboratory evaluation of sample collection methods (organs vs swabs) for
      Tasmanian salmon reovirus detection in farmed Atlantic salmon, Salmo salar L.
AB  - The use of swabs relative to organs as a sample collection method for the
      detection of Tasmanian salmon reovirus (TSRV) in farmed Tasmanian Atlantic
      salmon, Salmo salar L., was evaluated by RT-qPCR. Evaluation of individual and
      pooled sample collection (organs vs swabs) was carried out to determine the
      sensitivity of the collection methods and the effect of pooling of samples for
      the detection of TSRV. Detection of TSRV in individual samples was as sensitive
      when organs were sampled compared to swabs, and in pooled samples, organs
      demonstrated a sensitivity of one 10-fold dilution higher than sampling of pooled
      swabs. Storage of swabs at 4  degrees C for t = 24 h demonstrated results similar
      to those at t = 0. Advantages of using swabs as a preferred sample collection
      method for the detection of TSRV compared to organ samples are evident from these
      experimental trials.

PMID- 23121166
TI  - Insulin resistance predicts sustained virological response to treatment of
      chronic hepatitis C independently of the IL28b rs12979860 polymorphism.
AB  - BACKGROUND: Insulin resistance has been strongly associated with the attainment
      of sustained viral response (SVR) in hepatitis C patients. AIM: To determine, in
      a cohort of Spanish patients with chronic hepatitis C treated with peginterferon
      plus ribavirin (P+R), whether insulin resistance predicts SVR independently of
      interleukin-28B rs12979860 polymorphism. METHODS: Insulin resistance was measured
      as [HOMA-IR = Insulin (IU/mL)*glucose (mmol/L)/22.5]. Genotype, viral load and
      histological fibrosis using Scheuer score were also measured. Binary logistic
      regression analysis was used for statistical purposes. RESULTS: In a cohort of
      240 patients [78% genotype 1, 24% showing advanced fibrosis, 71% high viral load
      (>=800 000 IU/mL), 31% IL28b genotype CC and 50% with HOMA >2] treated with P+R,
      126 (53%) reached SVR. HOMA-IR index (HOMA <2: 63% vs. HOMA >2: 42%; P = 0.001
      and IL28b (genotype CC: 68% vs. genotype CT/TT: 45%; P = 0.002) were
      significantly associated with SVR. In multivariable logistic regression analysis
      in the overall cohort, variables independently associated were: viral genotype
      OR: 0.29 (95% CI: 0.11-0.78), P = 0.01; fibrosis OR: 1.62 (95% CI: 1.22-2.16), P
      = 0.001; HOMA-IR OR: 1.22 (95% CI: 1.02-1.47), P = 0.03; and IL28B genotype OR:
      2.43 (95% CI: 1.45-4.07), P = 0.001. The analyses also showed that degree of
      steatosis, HOMA-IR >2, mild fibrosis and IL28B CC genotype were significantly
      related to SVR in patients infected with HCV genotypes 1&4, but not in those with
      genotypes 2&3. No differences were seen in glucose, insulin level or HOMA-IR
      index segregated according to IL28B genotypes. CONCLUSION: Our results suggest
      that insulin resistance, fibrosis stage and IL28B polymorphisms were independent
      variables associated with sustained viral response.

PMID- 23121167
TI  - Cytoprotective signaling and gene expression in endothelial cells and macrophages
      lessons for atherosclerosis.
AB  - Atherosclerosis is a chronic inflammatory disease of the medium and large
      arteries driven in large part by the accumulation of oxidized low-density
      lipoproteins and other debris at sites rendered susceptible because of the
      geometry of the arterial tree. As lesions develop, they acquire a pathologic
      microcirculation that perpetuates lesion progression, both by providing a means
      for further monocyte and T-lymphocyte recruitment into the arterial wall and by
      the physical and chemical stresses caused by micro-hemorrhage. This review
      summarizes work performed in our department investigating the roles of signaling
      pathways, alone and in combination, that lead to specific programs of gene
      expression in the atherosclerotic environment. Focusing particularly on
      cytoprotective responses that might be enhanced therapeutically, the work has
      encompassed the anti-inflammatory effects of arterial laminar shear stress,
      mechanisms of induction of membrane inhibitors that prevent complement-mediated
      injury, homeostatic macrophage responses to hemorrhage, and the transcriptional
      mechanisms that control the stability, survival, and quiescence of endothelial
      monolayers. Lastly, while the field has been dominated by investigation into the
      mechanisms of DNA transcription, we consider the importance of parallel post
      transcriptional regulatory mechanisms for fine-tuning functional gene expression
      repertoires.

PMID- 23121168
TI  - Effect of exogenous testosterone on oxidative status of the testes in adult male
      rats.
AB  - The aim of this study was to investigate the testosterone-induced changes in the
      oxidative status of testes in adult male rats treated either with testosterone or
      after blockade of androgen receptors with cyproterone acetate. A total of 40
      intact rats were divided into four groups: a control group receiving sterile oil,
      the testosterone group receiving testosterone isobutyras, the cyproterone group
      receiving cyproterone acetate and the combination group receiving both
      testosterone isobutyras and cyproterone acetate. Treatments were carried out for
      2 days by intramuscular application. Parameters of oxidative stress and the
      expression levels of the steroidogenic acute regulatory protein (StAR) gene were
      measured in testes. Significantly increased TBARS and advanced glycation end
      products (AGEs) levels were found in the testosterone group when compared to the
      control group. The  degrees 1 ferric-reducing ability of the tissue and total
      antioxidative capacity were lower in the testosterone group in comparison with
      the control group. Gene expression analysis revealed significant downregulation
      of the StAR gene in the testes of rats in the testosterone and combination groups
      with respect to control animals. In conclusion, administration of exogenous
      testosterone influences the lipid peroxidation and carbonyl stress and decreases
      the antioxidant defence in the testes. These data might have implications for
      male fertility in humans. 

PMID- 23121169
TI  - Left ventricular asynchrony in patients with right bundle branch block and normal
      ejection fraction.
AB  - AIMS: The role of right bundle branch block (RBBB) for the induction of left
      ventricular (LV) asynchrony is discussed controversially. The objective of this
      study was to assess presence and degree of LV asynchrony in patients with RBBB,
      left bundle branch block (LBBB), or left anterior hemiblock (LAH) and normal LV
      function. METHODS: We included 15 patients with RBBB, 13 patients with RBBB and
      concomitant LAH, 10 patients with pure LBBB, and 100 healthy controls into this
      study. All patients had normal LV function. Interventricular asynchrony was
      assessed as the difference of the right and LV ejection delay. Intraventricular
      delay was obtained by tissue synchronicity imaging-guided tissue Doppler imaging
      measurement. RESULTS: Interventricular and left intraventricular asynchrony were
      linked to the presence of an LBBB. No left intraventricular asynchrony was noted
      during pure RBBB; interventricular delays were negative (aortic flow preceding
      pulmonary flow) in the presence of RBBB. CONCLUSION: In patients with normal LV
      function, intraventricular asynchrony depends on the presence of an LBBB and
      interventricular asynchrony is inversed in the presence of RBBB.

PMID- 23121170
TI  - Interpersonal self-support and attentional bias on negative and positive
      interpersonal information.
AB  - Interpersonal self-support is an indigenous Chinese personality concept. It
      represents the idealized notion of the kind of personality traits that help
      individuals deal with interpersonal problems and develop and maintain the
      harmonic and appropriate social relationships required in China's collectivistic
      and interdependent culture. It also was assumed to be a protective personality
      factor with regard to mental health and was found to be negatively related to
      psychosomatic symptoms. In the current study, cognitive processing of
      interpersonal information is assumed to be an underlying mechanism that connects
      interpersonal self-support with interpersonal relationships and mental health. To
      test this hypothesis, we conducted two experiments to investigate whether
      attentional bias on positive and negative interpersonal information was related
      to high and low interpersonal self-support. A spatial cueing task and the
      emotional Stroop task were administered to two samples of high and low
      interpersonal self-support Chinese undergraduate students to measure attentional
      bias. The results from both experiments suggested that high interpersonal self
      support students had an attentional bias toward positive interpersonal
      information, while low interpersonal self-support students preferentially
      attended to negative interpersonal information. Study 1 indicated that
      attentional bias toward positive interpersonal information was easily engaged in
      the high interpersonal self-support group, while attentional bias toward negative
      interpersonal information was both easy to engage and difficult to disengage in
      the low interpersonal self-support students. These results support our hypotheses
      that high interpersonal self-support people engage in positive processing of
      interpersonal information, whereas low interpersonal self-support people engage
      in negative processing of interpersonal information. The differential balance
      between positive and negative processing on interpersonal information may explain
      why interpersonal self-support predicts both mental health and interpersonal
      relationships. In addition, the relational schema may explain why interpersonal
      self-support is associated with an attentional bias toward interpersonal
      information. 

PMID- 23121171
TI  - The oral health of HIV-infected Brazilian children.
AB  - BACKGROUND: The number of HIV-infected people has increased almost continuously.
      Paediatric dentists should be concerned about the oral findings in HIV-infected
      children and their aetiologic factors, to promote adequate treatment. AIM: To
      present the oral health aspects of Brazilian HIV-infected children and to verify
      the aetiological factors. DESIGN: A cross-sectional study was conducted with HIV
      infected children. During the medical appointments, children were submitted to
      visual-tactile exams of oral soft tissues and teeth. All parents answered
      questions in a structured interview. Data were analysed using the SPSS, release
      10.0 (Chicago, IL, USA). RESULTS: Of the 57 children examined, 39 (69.6%)
      presented one or more oral soft tissue manifestations. More than a half suffered
      from gingivitis and only 12.5% had no visible dental biofilm. A high prevalence
      of dental surfaces with active carious lesions was observed; mean DMFS-m and dmfs
      m scores were 5.41 +/- 5.61 and 16.77 +/- 19.52, respectively. Caries activity
      and gingivitis were correlated with the presence of mature dental biofilm.
      CONCLUSIONS: Prevalence of soft tissue lesions, dental caries and gingivitis in
      HIV-infected children was high and correlated to lack of satisfactory oral
      hygiene habits, suggesting the need of therapeutic programmes that allow these
      children to recover their oral health.

PMID- 23121176
TI  - Solid-phase synthesis of 4,7,8-trisubstituted 1,2,3,4-tetrahydro
      benzo[e][1,4]diazepin-5-ones.
AB  - Solid-phase synthesis of 1,2,3,4-tetrahydro-benzo[e][1,4]diazepin-5-ones with use
      of polystyrene resin is described. The starting material was polymer supported
      1,2-diaminoethane and as a key synthon, 4-chloro-2-fluoro-5-nitrobenzoic acid was
      used. The synthetic approach allows the preparation of derivatives with variable
      substitution at positions 4 and 8. Additionally, a skeletal diversity was
      increased when the nitro group was reduced and some benzene fused heterocycles
      were prepared. An expansion of a diazepinone to a benzodiazocinone scaffold was
      also successful although some limitations in a diversity of target derivatives
      were observed.

PMID- 23121175
TI  - Surface modification of silicone for biomedical applications requiring long-term
      antibacterial, antifouling, and hemocompatible properties.
AB  - Silicone has been used for peritoneal dialysis (PD) catheters for several
      decades. However, bacteria, platelets, proteins, and other biomolecules tend to
      adhere to its hydrophobic surface, which may lead to PD outflow failure, serious
      infection, or even death. In this work, a cross-linked poly(poly(ethylene glycol)
      dimethacrylate) (P(PEGDMA)) polymer layer was covalently grafted on medical-grade
      silicone surface to improve its antibacterial and antifouling properties. The
      P(PEGDMA)-grafted silicone (Silicone-g-P(PEGDMA)) substrate reduced the adhesion
      of Staphylococcus aureus , Escherichia coli , and Staphylococcus epidermidis , as
      well as 3T3 fibroblast cells by >=90%. The antibacterial and antifouling
      properties were preserved after the modified substrate was aged for 30 days in
      phosphate buffer saline. Further immobilization of a polysulfobetaine polymer,
      poly((2-(methacryloyloxy)ethyl)dimethyl-(3-sulfopropyl)ammonium hydroxide)
      (P(DMAPS)), on the Silicone-g-P(PEGDMA) substrate via thiol-ene click reaction
      leads to enhanced antifouling efficacy and improved hemocompatibility with the
      preservation of the antibacterial property. Compared to pristine silicone, the so
      obtained Silicone-g-P(PEGDMA)-P(DMAPS) substrate reduced the absorption of bovine
      serum albumin and bovine plasma fibrinogen by >=80%. It also reduced the number
      of adherent platelets by >=90% and significantly prolonged plasma recalcification
      time. The results indicate that surface grafting with P(PEGDMA) and P(DMAPS) can
      be potentially useful for the modification of silicone-based PD catheters for
      long-term applications.

PMID- 23121177
TI  - Antisaccades as decisions: LATER model predicts latency distributions and error
      responses.
AB  - Antisaccades are widely used in the study of voluntary behavioural control: a
      subject told to look in the opposite direction to a stimulus must suppress the
      automatic response of looking towards it, leading to delays and errors that are
      commonly believed to be generated by competing decision processes. However,
      currently we lack a precise model of the details of antisaccade behaviour, or
      indeed detailed quantitative data in the form of full reaction time distributions
      by which any such model could be evaluated. We measured subjects' antisaccade
      latency distributions and error rates, and found that we could account precisely
      for both distributions and errors with a model having three competing LATER
      processes racing to threshold. In an even more stringent test, we manipulated
      subjects' expectation of the stimulus, leading to large changes in behaviour that
      were nevertheless still accurately predicted. The antisaccade task is widely used
      in the laboratory and clinic because of the relative complexity and vulnerability
      of the underlying decision mechanisms: our model, grounded in detailed
      quantitative data, is a robust way of conceptualizing these processes.

PMID- 23121179
TI  - The rotavirus saga revisited.
AB  - Two live oral rotavirus vaccines were approved by the US Food and Drug
      Administration in 2005 and 2008, following large studies of ~70,000 each in order
      to address questions about intussusception triggered by a third earlier vaccine.
      Both new rotavirus vaccines showed almost identical rates of intussusception in
      vaccine and placebo recipients. These vaccines have been used extensively in the
      United States with positive results. Efforts are under way to implement these
      vaccines in developing countries where the need is greatest.

PMID- 23121178
TI  - Association of mycophenolic acid dose with efficacy and safety events in kidney
      transplant patients receiving tacrolimus: an analysis of the Mycophenolic acid
      Observational REnal transplant registry.
AB  - BACKGROUND: Dose-finding studies for mycophenolic acid (MPA) in tacrolimus
      treated kidney transplant patients are lacking. METHODS: Data from 901 de novo
      kidney transplant recipients enrolled in the prospective, non-interventional
      Mycophenolic acid Observational REnal (MORE) transplant registry were analyzed
      according to baseline daily MPA dose (<2000, 2000 or >2000 mg). RESULTS: The
      proportion of patients receiving 2000 and <2000 mg was 77.6% and 19.9% at
      baseline, 74.5% and 23.3% at month 1, 62.4% and 35.5% at month 3, 48.5% and 50.2%
      at month 6, and 44.1% and 55.2% at month 12. More patients were maintained on
      2000 mg with enteric-coated mycophenolate sodium (EC-MPS) vs. mycophenolate
      mofetil (month 6, 52.7% vs. 43.0% [p=0.02]; month 12, 47.3% vs. 39.4% [p=0.08]).
      Multivariate modeling showed no significant effect of baseline MPA dose on 12
      month risk of biopsy-proven acute rejection, graft loss or estimated GFR, or on
      safety events including MPA discontinuation other than a higher rate of
      gastrointestinal adverse events in patients with an initial MPA dose>2000 mg
      (p=0.029) vs. 2000 mg. CONCLUSIONS: These findings suggest that an initial MPA
      dose of <2000 mg does not compromise 12-month efficacy in tacrolimus-treated
      kidney transplants, but controlled trials are required and the lower threshold
      for MPA dose remains to be defined.

PMID- 23121181
TI  - Reduced-intensity hematopoietic stem cell transplants for malignancies:
      harnessing the graft-versus-tumor effect.
AB  - Allogeneic hematopoietic cell transplantation combines the power of cytotoxic
      chemo/radiotherapy with the ability of the new immune system to seek out and
      destroy tumor cells. However, administration of such myeloablative transplants is
      fraught with risks, some of which are related to the intensive conditioning
      regimens. Reductions in the intensity of the administered cytotoxic therapy have
      demonstrated that under some circumstances, the burden of fighting tumor and
      enhancing stem cell engraftment can be shouldered mostly by the transplanted
      immune system. Reduced intensity has allowed a potentially curative therapy for
      hematologic malignancies to be offered to an expanded patient population. Ongoing
      research seeks to enhance the safety and power of this form of allogeneic
      immunotherapy.

PMID- 23121180
TI  - Defective complement inhibitory function predisposes to renal disease.
AB  - The role of the complement system in mediating human renal disease has long been
      recognized in immune-complex excess syndromes such as systemic lupus
      erythematosus and in dense deposit disease in which no immunoglobulin (Ig) is
      present. Over the past 15 years, mutations in complement regulatory genes have
      been demonstrated to predispose to thrombotic microangiopathies including
      atypical hemolytic uremic syndrome, C3 and C1q glomerulopathies, and
      preeclampsia. Excessive complement activation on an endothelial cell, due to
      either an autoantibody or a regulatory protein deficiency, sets up a procoagulant
      state in these diseases as well as in the antiphospholipid syndrome. Knowledge of
      the genes involved and the functional consequences of alterations in their
      structure has led to therapy that blocks complement activation.

PMID- 23121182
TI  - Duty-hour limits and patient care and resident outcomes: can high-quality studies
      offer insight into complex relationships?
AB  - Long hours are an accepted component of resident education, yet data suggest they
      contribute to fatigue that may compromise patient safety. A systematic review
      confirms that limiting duty hours increases residents' hours of sleep and
      improves objective measures of alertness. Most studies of operative experience
      for surgical residents found no effect, and there is evidence of a limited
      positive effect on residents' mood. We find a mixed effect on patient safety,
      although problems with supervision, rather than the limits, may be responsible or
      contibute; evidence of reduced continuity of care and reduced continuity in
      residents' clinical education; and evidence that increased workload under the
      limits has a negative effect on patient and resident outcomes. We highlight
      specific areas for research and offer recommendations for national policy.

PMID- 23121183
TI  - Cytokines, obesity, and cancer: new insights on mechanisms linking obesity to
      cancer risk and progression.
AB  - Obesity is a problem of epidemic proportions in many developed nations. Increased
      body mass index and obesity are associated with a significantly worse outcome for
      many cancers. Breast cancer risk in the postmenopausal setting and poor disease
      outcome for all patients is significantly augmented in overweight and obese
      individuals. The expansion of fat tissue involves a complex interaction of
      endocrine factors known as adipokines and cytokines. High cytokine levels in
      primary breast cancers and in the circulation of affected patients have been
      associated with poor outcome. This review summarizes the how cytokine production
      in obese adipose tissue creates a chronic inflammatory microenvironment that
      favors tumor cell motility, invasion, and epithelial-mesenchymal transition to
      enhance the metastatic potential of tumor cells. Many of the cytokines associated
      with a proinflammatory state are not only upregulated in obese adipose tissue but
      may also stimulate the self-renewal of cancer stem cells. Thus, enhanced cytokine
      production in obese adipose tissue may serve both as a chemoattractant for
      invading cancers and to augment their malignant potential. These new mechanistic
      insights suggest that the current obesity epidemic will presage a significant
      increase in cancer incidence, morbidity, and mortality in the next few decades.

PMID- 23121185
TI  - Biomechanics of anther opening.

PMID- 23121186
TI  - Mitochondrial genome invaders: an unselfish role as molecular markers.

PMID- 23121187
TI  - The North American Mycoflora project - the first steps on a long journey.

PMID- 23121188
TI  - Plant evolutionary ecology: molecular genetics, global warming and invasions, and
      the novel approaches we are using to study adaptations.

PMID- 23121189
TI  - Rescue corticosteroids in twin pregnancies and short-term neonatal outcomes.
AB  - OBJECTIVE: To estimate the efficacy of a rescue course of antenatal
      corticosteroids in twin pregnancies. DESIGN: Retrospective cohort study. SETTING:
      Tertiary-care centre. POPULATION: Twins born from 24 to <34 weeks of gestation in
      a single maternal and fetal medicine practice from 2006 to 2011. METHODS: We
      compared neonatal outcomes in 88 twins exposed to a single course of
      corticosteroids with outcomes in 42 twins exposed to two courses of
      corticosteroids: the initial course and a single rescue course. Analyses were
      adjusted to control for correlation between twins born to the same mother. MAIN
      OUTCOME MEASURE: Short-term neonatal respiratory morbidity. RESULTS: Rescue
      corticosteroids were associated with fewer days of mechanical ventilation (7.3 +/
      3.3 versus 33.9 +/- 25.3 days, P = 0.003), fewer days with a fraction of
      inspired oxygen of >21% (6.3 +/- 4.3 versus 33.3 +/- 25.8 days, P = 0.003), a
      lower incidence of mechanical ventilation >14 days or death while on mechanical
      ventilation (0 versus 12.5%, P = 0.016), and a lower incidence of retinopathy of
      prematurity (0 versus 12.5%, P = 0.016). The proportion of neonates with
      respiratory distress syndrome did not differ between the groups (adjusted odds
      ratio 1.28, 95% confidence interval 0.50-3.26). There were no differences found
      for birthweight, head circumference and length. CONCLUSIONS: In twins born before
      34 weeks of gestation, exposure to rescue corticosteroids may be associated with
      improved neonatal outcomes. Further studies are warranted to assess the effect of
      rescue corticosteroids in twin pregnancies.

PMID- 23121190
TI  - Incidence of hyperbilirubinemia and jaundice due to atazanavir in a cohort of
      Hispanic patients.

PMID- 23121191
TI  - Population genomic signatures of divergent adaptation, gene flow and hybrid
      speciation in the rapid radiation of Lake Victoria cichlid fishes.
AB  - Adaptive radiations are an important source of biodiversity and are often
      characterized by many speciation events in very short succession. It has been
      proposed that the high speciation rates in these radiations may be fuelled by
      novel genetic combinations produced in episodes of hybridization among the young
      species. The role of such hybridization events in the evolutionary history of a
      group can be investigated by comparing the genealogical relationships inferred
      from different subsets of loci, but such studies have thus far often been
      hampered by shallow genetic divergences, especially in young adaptive radiations,
      and the lack of genome-scale molecular data. Here, we use a genome-wide sampling
      of SNPs identified within restriction site-associated DNA (RAD) tags to
      investigate the genomic consistency of patterns of shared ancestry and adaptive
      divergence among five sympatric cichlid species of two genera, Pundamilia and
      Mbipia, which form part of the massive adaptive radiation of cichlids in the East
      African Lake Victoria. Species pairs differ along several axes: male nuptial
      colouration, feeding ecology, depth distribution, as well as the morphological
      traits that distinguish the two genera and more subtle morphological differences.
      Using outlier scan approaches, we identify signals of divergent selection between
      all species pairs with a number of loci showing parallel patterns in replicated
      contrasts either between genera or between male colour types. We then create SNP
      subsets that we expect to be characterized to different extents by selection
      history and neutral processes and describe phylogenetic and population genetic
      patterns across these subsets. These analyses reveal very different evolutionary
      histories for different regions of the genome. To explain these results, we
      propose at least two intergeneric hybridization events (between Mbipia spp. and
      Pundamilia spp.) in the evolutionary history of these five species that would
      have lead to the evolution of novel trait combinations and new species.

PMID- 23121193
TI  - Are immediate- and extended-release drugs interchangeable?

PMID- 23121192
TI  - Autophagy and bacterial clearance: a not so clear picture.
AB  - Autophagy, an intracellular degradation process highly conserved from yeast to
      humans, is viewed as an important defence mechanism to clear intracellular
      bacteria. However, recent work has shown that autophagy may have different roles
      during different bacterial infections that restrict bacterial replication
      (antibacterial autophagy), act in cell autonomous signalling (non-bacterial
      autophagy) or support bacterial replication (pro-bacterial autophagy). This
      review will focus on newfound interactions of autophagy and pathogenic bacteria,
      highlighting that, in addition to delivering bacteria to the lysosome, autophagy
      responding to bacterial invasion may have a much broader role in mediating
      disease outcome.

PMID- 23121194
TI  - Tailored immunoconjugate therapy depending on a quantity of tumor stroma.
AB  - The purpose of this study was to clarify the appropriate combination of targeting
      antibody and conjugate-design of anti-tumor immunoconjugate depending on a
      quantity of tumor stroma. Most human solid tumors including pancreatic cancer
      (PC) forming hypovascular and stroma-rich tumor hinders the penetration of
      monoclonal antibodies (mAbs) into the cells, and that leads to failure of the
      conventional cell-targeting immunoconjugate strategy. To overcome this drawback,
      SN-38 as topoisomerase 1 inhibitor was conjugated to a mAb to collagen 4, a
      plentiful component of the tumor stroma via ester-bond. The immunoconjugate,
      which was able to release SN-38 in physiological condition outside the cells, was
      effective to stroma-rich PC-tumor. On the other hand, anti-CD 20 mAb-PEG-SN-38
      via carbamate-bond as conventional immunoconjugate, enabled SN-38 to be released
      by a carboxylesterase inside of the tumor cell following the internalization,
      showed strong anti-tumor activity against malignant lymphoma as hypervascular and
      stroma-poor tumor. The conjugate-design, in parallel with the choice of targeting
      antibodies, should be selected to maximize the therapeutic effect in each
      individual tumor having a distinct stromal structure.

PMID- 23121195
TI  - Development of an equine-tropic replication-competent lentivirus assay for equine
      infectious anemia virus-based lentiviral vectors.
AB  - The release of lentiviral vectors for clinical use requires the testing of vector
      material, production cells, and, if applicable, ex vivo-transduced cells for the
      presence of replication-competent lentivirus (RCL). Vectors derived from the
      nonprimate lentivirus equine infectious anemia virus (EIAV) have been directly
      administered to patients in several clinical trials, with no toxicity observed to
      date. Because EIAV does not replicate in human cells, and because putative RCLs
      derived from vector components within human vector production cells would most
      likely be human cell-tropic, we previously developed an RCL assay using
      amphotropic murine leukemia virus (MLV) as a surrogate positive control and human
      cells as RCL amplification/indicator cells. Here we report an additional RCL
      assay that tests for the presence of theoretical "equine-tropic" RCLs. This
      approach provides further assurance of safety by detecting putative RCLs with an
      equine cell-specific tropism that might not be efficiently amplified by the human
      cell-based RCL assay. We tested the ability of accessory gene-deficient EIAV
      mutant viruses to replicate in a highly permissive equine cell line to direct our
      choice of a suitable EIAV-derived positive control. In addition, we report for
      the first time the mathematical rationale for use of the Poisson distribution to
      calculate minimal infectious dose of positive control virus and for use in
      monitoring assay positive/spike control failures in accumulating data sets. No
      RCLs have been detected in Good Manufacturing Practice (GMP)-compliant RCL assays
      to date, further demonstrating that RCL formation is highly unlikely in
      contemporary minimal lentiviral vector systems.

PMID- 23121196
TI  - A cross-sectional study of hand sensation in adults with conservatively treated
      obstetric brachial plexus lesion.
AB  - AIM: Sensory function is assumed to recover almost completely in obstetric
      brachial plexus lesion (OBPL), and is reported to recover much better than motor
      function. However, there is no obvious physiological reason why this should be
      so. Any persistent problems with sensory innervation might contribute to
      disability, therefore we aimed to assess sensory dysfunction in adults resulting
      from OBPL. METHOD: Adults with conservatively treated OBPL (n=17; 12 females,
      five males; median age 38y; lesion levels: C5-C6, n=7; C5-C7, n=7; C5-C8, n=2; C5
      Th1, n=1) and 19 healthy comparison persons (10 females, nine males; median age
      23y) were investigated. Sensory function was measured using Semmes-Weinstein
      monofilaments, two-point discrimination, object recognition, and a locognosia
      test. RESULTS: Scores of the Semmes-Weinstein monofilaments and two-point
      discrimination, but not object recognition or locognosia, were significantly
      worse in those with OBPL than in those without OBPL. INTERPRETATION: There may be
      systematic abnormalities in sensory function in adults with conservatively
      treated OBPL. The existence of these impairments and their contribution to
      functional impairment needs to be acknowledged.

PMID- 23121197
TI  - Analysis of the global methylation status of human spermatozoa and its
      association with the tendency of these cells to enter apoptosis.
AB  - The methylation status of human spermatozoa has been examined in relation to the
      isopycnic density of these cells and their tendency to spontaneously default to
      an apoptotic state. DNA methylation was evaluated using three independent
      procedures: high-pressure liquid chromatography, flow cytometry and
      immunocytochemistry. All three techniques revealed that poor-quality spermatozoa
      recovered from the low-density region of Percoll gradients were characterised by
      a global hypermethylation of their DNA. Hypermethylation was visualised with an
      anti-5-methylcytosine antibody as punctate areas of cross-reactivity randomly
      distributed throughout the chromatin. Immunocytochemical evidence was also
      obtained suggesting that the sperm mitochondrial genome exists in a heavily
      methylated state, as a possible buffer against unscheduled transcription.
      Defective human spermatozoa were also shown to exhibit a tendency to default to
      an apoptotic state characterised by an increase in annexin V binding. The
      measurement of annexin V binding levels in individual sperm populations was found
      to be highly correlated with sperm vitality (P < 0.001) and the methylation
      status of their DNA (P < 0.001). We conclude that the generation of defective,
      apoptotic human spermatozoa is associated with disorders of spermatogenesis that
      lead to a global hypermethylation of their nuclear DNA. 

PMID- 23121198
TI  - Development and validation of a real-time PCR assay for the detection of
      Aeromonas salmonicida.
AB  - A real-time PCR assay using a molecular beacon was developed and validated to
      detect the vapA (surface array protein) gene in the fish pathogen, Aeromonas
      salmonicida. The assay had 100% analytical specificity and analytical
      sensitivities of 5 +/- 0 fg (DNA), 2.2 * 10(4) +/- 1 * 10(4) CFU g(-1) (without
      enrichment) and 40 +/- 10 CFU g(-1) (with enrichment) in kidney tissue. The assay
      was highly repeatable and proved to be robust following equivalency testing using
      a different real-time PCR platform. Following analytical validation, diagnostic
      specificity was determined using New Zealand farmed Chinook salmon, Oncorhynchus
      tshawytscha (Walbaum), (n = 750) and pink shubunkin, Carassius auratus (L.) (n =
      157). The real-time PCR was run in parallel with culture and all fish tested were
      found to be negative by both methods for A. salmonicida, resulting in 100%
      diagnostic specificity (95% confidence interval). The molecular beacon real-time
      PCR system is specific, sensitive and a reproducible method for the detection of
      A. salmonicida. It can be used for diagnostic testing, health certification and
      active surveillance programmes.

PMID- 23121199
TI  - Rapid immunostaining in Mohs: current applications and attitudes.
AB  - BACKGROUND: Rapid immunostaining in Mohs micrographic surgery (MMS) has been
      extensively reviewed in the recent literature. Despite the recent attention,
      there is relatively little information on how frequently these techniques are
      actually utilized and the current attitudes of the Mohs community towards
      immunohistochemical (IHC) stains. OBJECTIVE: We attempted to obtain information
      on the utilization and attitudes towards the use of rapid immunostaining in Mohs
      through a survey of fellowship-trained Mohs surgeons. MATERIALS AND METHODS: A
      twenty-five question survey was sent to members of the American College of Mohs
      Surgery (ACMS) through various methods including SurveyMonkey((r)) , email, fax,
      and Metrofax((r)) . RESULTS: A total of 378 surveys were completed. These
      responses represent a cross-section of fellowship-trained members of the ACMS.
      CONCLUSIONS: The vast majority of respondents felt as though IHC stains could be
      used reliably in Mohs. A subset of responses indicated that the most common
      reasons for not using IHC stains are time consumption, lack of education, and
      startup and/or maintenance costs. An increase in immunostain usage over 10 years
      ago appears to correlate with the activity in the literature. There may be an
      underutilization of IHC staining in fellowship programs, as indicated by
      respondents' opinions.

PMID- 23121201
TI  - Myocardial protection era: from valve surgery to heart transplantation.

PMID- 23121200
TI  - Short-term efficacy of tacrolimus in steroid-refractory ulcerative colitis -
      experience in 130 patients.
AB  - BACKGROUND: Steroid-refractory ulcerative colitis (UC) remains a challenging
      condition warranting surgery upon failure of pharmacological treatment.
      Calcineurin inhibitors or infliximab are alternatives in this situation. Data on
      the efficacy and safety of tacrolimus in this setting are limited. AIM: To study
      the short-term efficacy and safety of tacrolimus in moderate-to-severe steroid
      refractory UC. The role of thiopurines in this situation and predictors of
      colectomy were evaluated. METHODS: In three centers, all charts from tacrolimus
      treated patients with steroid-refractory UC were reviewed. Efficacy was assessed
      by colectomy-free survival and clinical remission at 3 months. RESULTS: We
      identified 130 patients with pancolitis in 75 (59%), left-sided disease in 35
      (27%) and proctitis in 18 patients (14%) (disease localisation not obtainable in
      two patients). The median age was 40 (range: 18-81). Clinical activity according
      to the median Lichtiger score decreased from 13 (range: 4-17) at baseline to 3 (0
      14) at week 12. Eighteen patients underwent colectomy within the first 3 months
      of treatment with tacrolimus (14%). Clinical remission was achieved in 94
      patients (72%) in this period. Thiopurines given in parallel to tacrolimus tended
      to limit colectomy and significantly increased remission (P = 0.002) in the short
      term. No other predictors of colectomy or remission were identified. Side effects
      were noticed in 53% of patients and no severe events occurred. CONCLUSION: This
      large survey confirms the efficacy and safety of tacrolimus in patients with
      steroid-refractory ulcerative colitis.

PMID- 23121202
TI  - Impact of a unique international conference on pediatric mechanical circulatory
      support and pediatric cardiopulmonary perfusion research.
AB  - There is no question that the International Conference on Pediatric Mechanical
      Circulatory Support Systems and Pediatric Cardiopulmonary Perfusion is a unique
      event that has had a significant impact on the treatment of neonatal, infantile,
      and pediatric cardiopulmonary patients around the globe since 2005. This annual
      event will continue as long as there is a need to fill the gap for underserved
      patient population. It will also continue to recognize promising young
      investigators based on their full manuscripts for young investigator awards.

PMID- 23121203
TI  - Response expectancy versus response hope in predicting birth-related emotional
      distress and pain.
AB  - Response expectancies and response hopes have been shown to be two distinct
      constructs with important implications for nonvolitional outcomes. More
      specifically, studies show that response expectancies: (1) are sufficient to
      cause nonvolitional outcomes, (2) are not mediated by other psychological
      variables, and (3) are self-confirming while seemingly automatic. A new
      programmatic research line has differentiated between people's response
      expectancies and their response hopes regarding nonvolitional outcomes and showed
      that even if response hope and response expectancy are separate constructs, they
      are not unrelated. These concepts have not yet been studied in pregnant women.
      Moreover, determining the causal factors that best explain the variance of
      emotional distress and pain in pregnancy is of great importance. Thus, the aim of
      this study was to investigate the interrelations between response expectancy and
      response hope in pregnant women with respect to (1) emotional distress prior to
      giving birth and (2) pain during giving birth. Additionally, self-reported labor
      hours were analyzed as a secondary outcome. Results show that response expectancy
      for pain directly predicts pain, and that the discrepancy between response hopes
      and response expectancies is a strong predictor of investigated outcomes. Thus,
      our results support the idea that preventive psychological interventions for
      pregnant women should emphasize adjusting response expectancies and response
      hopes regarding the pain and emotional distress associated with giving birth. We
      believe that the results have both theoretical and practical implications and the
      topic deserves further investigation. 

PMID- 23121204
TI  - British Association of Dermatologists' guidelines for the management of bullous
      pemphigoid 2012.

PMID- 23121205
TI  - Segregative clustering of Lo and Ld membrane microdomains induced by local pH
      gradients in GM1-containing giant vesicles: a lipid model for cellular
      polarization.
AB  - Several cell polarization processes are coupled to local pH gradients at the
      membrane surface. We have investigated the involvement of a lipid-mediated effect
      in such coupling. The influence of lateral pH gradients along the membrane
      surface on lipid microdomain dynamics in giant unilamellar vesicles containing
      phosphatidylcholine, sphingomyelin, cholesterol, and the ganglioside GM1 was
      studied. Lo/Ld phase separation was generated by photosensitization. A lateral pH
      gradient was established along the external membrane surface by acid local
      microinjection. The gradient promotes the segregation of microdomains: Lo domains
      within an Ld phase move toward the higher pH side, whereas Ld domains within an
      Lo phase move toward the lower pH side. This results in a polarization of the
      vesicle membrane into Lo and Ld phases poles in the axis of the proton source. A
      secondary effect is inward tubulation in the Ld phase. None of these processes
      occurs without GM1 or with the analog asialo-GM1. These are therefore related to
      the acidic character of the GM1 headgroup. LAURDAN fluorescence experiments on
      large unilamellar vesicles indicated that, with GM1, an increase in lipid packing
      occurs with decreasing pH, attributed to the lowering of repulsion between GM1
      molecules. Packing increase is much higher for Ld phase vesicles than for Lo
      phase vesicles. It is proposed that the driving forces for domain vectorial
      segregative clustering and vesicle polarization are related to such differences
      in packing variations with pH decrease between the Lo and Ld phases. Such pH
      driven domain clustering might play a role in cellular membrane polarization
      processes in which local lateral pH gradients are known to be important, such as
      migrating cells and epithelial cells.

PMID- 23121206
TI  - Melanotan II injection resulting in systemic toxicity and rhabdomyolysis.
AB  - INTRODUCTION: Melanotan products are currently purchased over the Internet and
      are designed to induce melanogenesis to create sunless tanning as well are used
      as sexual stimulants. We report a novel case of systemic toxicity with
      sympathomimetic excess and rhabdomyolysis after use of Melanotan II. CASE REPORT:
      A 39 year-old Caucasian male injected subcutaneously 6 mg of Melanotan II
      purchased over the Internet in an attempt to darken his skin during wintertime.
      This dose was six times the recommended starting dose per the patient. In the
      emergency department two hours post injection, he complained of diffuse body
      aches, sweating, and a sensation of anxiety. Vital signs included BP 151/85 mmHg,
      HR 130 bpm that peaked at 146 bpm, and temperature of 97.8 degrees F. Physical
      exam demonstrated a restless and anxious appearing male with mydriasis,
      diaphoresis, tachycardia, and diffuse muscle tremors. Pertinent laboratory values
      were creatinine 2.25 mg/dL, CPK 1760 IU/L, troponin 0.23 ng/mL, WBC 19.1 k/MUL.
      Urinalysis demonstrated 3 + blood with red cell casts but 0-2 RBC/hpf.
      Qualitative urine drug screen was negative for metabolites of cocaine and
      amphetamines but positive for opiates. The patient received benzodiazepines for
      agitation and anxiety and had improvement in his symptoms. He was admitted to the
      ICU and during hospitalization his CPK elevated to 17773 IU/L 12 hours later. He
      continued to receive intravenous fluids with sodium bicarbonate for
      rhabdomyolysis and his CPK decreased to 2622 IU/L with improvement of creatinine
      to 1.23 mg/dL upon discharge from the ICU after 3 days. The substance, which he
      injected, was analyzed via mass spectrometry and was confirmed to be Melanotan II
      when compared with an industry purchased standard sample. DISCUSSION: Melanotan
      products are purchased via the Internet and have three main formulations
      (Melanotan I, Melanotan II, and bremelanotide). Melanotan I increases
      melanogenesis and eumelanin content to produce sunless tanning. Melanotan II also
      increases skin pigmentation but also produces spontaneous penile erections and
      sexual stimulation. Bremelanotide is a variation of Melanotan II that is
      specifically designed for sexual stimulation. This unique case highlights the
      potential of systemic toxicity with sympathomimetic excess, rhabdomyolysis, and
      renal dysfunction from Melanotan II use. CONCLUSION: Melanotan II use resulted in
      systemic toxicity including apparent sympathomimetic symptoms, rhabdomyolysis,
      and renal dysfunction.

PMID- 23121207
TI  - Does communication skills training make a difference to patients' experiences of
      consultations in oncology and palliative care services?
AB  - There is much evidence supporting the efficacy of communication skills training;
      however, very little of this evidence comes from patient feedback. The primary
      aim of this pilot study was to evaluate whether the advanced communications
      skills training improves patients' experience of consultations. Healthcare
      professionals working in oncology and palliative care services from the North
      East of England were invited to participate in this study. Interactions between
      healthcare professionals (n = 21) and patients (n = 1103) were evaluated using
      the Consultation and Relational Empathy (CARE) Measure, which is a brief
      questionnaire designed to assess the patients' perceptions of relational empathy
      in the consultation. Additional demographic variables, such as patient age,
      length of consultation, familiarity with healthcare professional and overall
      satisfaction with consultation, were also collected. Healthcare professionals
      were either part of the intervention group who attended a 3-day communication
      skills training course or part of the control group who were on the waiting list
      for training. No differences in the patients' ratings on the CARE measure were
      found between Time 1 (before training) and Time 2 (after training) for the
      intervention group. Possible explanations for the findings are explored and
      implications for communication skills training are discussed.

PMID- 23121209
TI  - Action control of exercise behavior: evaluation of social cognition, cross
      behavioral regulation, and automaticity.
AB  - Intention is considered the proximal determinant of behavior in many popular
      theories applied to understanding physical activity, yet intention-behavior
      discordance is high. Thus, an understanding of constructs that facilitate or
      inhibit the successful translation of intentions into behavior is both timely and
      important. The action control approach of dividing the intention-behavior
      relationship into quadrants of successful/unsuccessful intenders has shown
      utility in the past by demonstrating the magnitude of intention-behavior
      discordance and allowing for an outcome variable to test predictors. The purpose
      of this article was to evaluate automaticity and cross-behavioral regulation as
      predictors of exercise action control, in conjunction with other more standard
      social cognitive predictors of perceived behavioral control and affective and
      instrumental attitudes. Participants were a random sample of 263 college students
      who completed predictor measures at time one, followed by exercise behavior two
      weeks later. Participants were classified into three intention-behavior profiles:
      (1) nonintenders (14.1%; n = 31), (2) unsuccessful intenders (35.5%; n = 78), and
      (3) successful intenders (48.6%; n = 107). Affective attitude, perceived
      behavioral control, automaticity, and cross-behavioral regulation were predictors
      of action control. The results demonstrate that automaticity and cross-behavioral
      regulation, constructs not typically used in intention-based theories, predict
      intention-behavior discordance.

PMID- 23121208
TI  - Social control in older adults' diabetes self management and well-being.
AB  - The "dual effects" hypothesis argues that social control can be effective in
      promoting positive health-related behavior change, but it can also jeopardize the
      targeted individual's well-being. This hypothesis is tested using hemoglobin A1C
      as an objective indicator of behavioral compliance with diabetes self-management
      behavior and depressive symptoms. Differences in the effects of social control on
      A1C and depressive symptoms by sex and ethnicity are tested.   Cross-sectional
      data were obtained from a multi-ethnic sample of older adults with diabetes (N =
      593). Greater social control was associated with poorer rather than better odds
      of achieving glucose control, and with greater depressive symptoms. There was no
      evidence that social control has differential effects on either glucose control
      or depressive symptoms by sex or ethnicity. Active use of social control attempts
      by family members and friends, especially if they are coercive or punitive in
      nature, are likely counterproductive for maintaining the physical and mental
      health of older adults with diabetes.

PMID- 23121210
TI  - The experience of teasing in elective cosmetic surgery patients.
AB  - The role of teasing as a motivator for patients undertaking elective cosmetic
      surgery was investigated. Pre-operative data were collected, using a range of
      standardized tests in addition to open ended questions about their experience of
      teasing, from 449 patients aged 18 to 70 undergoing elective cosmetic surgery in
      Australia. Just under half of the sample indicated that they had been teased or
      bullied about their appearance. Teased patients showed significantly higher
      levels of anxiety, depression and dysmorphic concern; lower levels of physical
      attractiveness and appearance satisfaction; and lower levels of satisfaction with
      discrete aspects of their appearance than nonteased patients. Teasing also
      contributed to longer periods of considering surgery as an answer to body
      dissatisfaction concerns, even when controlling for age. Prevention education
      initiatives on appearance-related teasing should be targeted at school students.
      This, along with earlier detection of the psychological impacts of weight and
      appearance-related teasing, fewer people, if offered strategies for coping
      through counseling, may contemplate surgery as a response to this teasing.

PMID- 23121211
TI  - Sex differences in the association between prenatal smoking and decreased
      birthweight, and intensive health care of the neonate.
AB  - Gender-specific associations between prenatal smoking and birthweight, and
      neonate intensive health care were studied. Cross-sectional data from 11,583
      newborns in the continuous National Health and Nutrition Examination Survey
      (NHANES) 2003-2008 early childhood data sets were used. Change in infant
      birthweight and likelihood of receiving neonatal intensive care by prenatal
      smoking exposure were assessed. Multivariable regression models were used to
      assess the influence of prenatal smoking on birthweight and likelihood of
      receiving intensive neonatal health care. Compared with infants from nonsmoking
      mothers, prenatal smoking associated with significant decrease in infant
      birthweight, -203.0 g +/- 32.5, P < 0.001. The change in birthweight differed
      between infant boys, -220.2 g +/- 44.5, and girls, -184.1 g +/- 38.8. Newborns
      exposed to prenatal smoking were more likely to have low birthweight, odds ratio
      1.46, P < 0.03, and to receive neonatal intensive health care, odds ratio 1.20; P
      < 0.04. It is imperative that prenatal counseling emphasizes prenatal maternal
      smoking.

PMID- 23121213
TI  - Terlipressin in brain-death donors.
AB  - BACKGROUND: Metabolic management of brain-death organ donors includes correction
      of the hormonal perturbations that occur after cerebral death and impair
      circulatory function. Vasopressin is a hormone secreted by the posterior
      pituitary gland, which contributes to maintain systemic blood pressure by
      regulating urine secretion and small arteriole tonus. During brain death, the
      pituitary gland is damaged and hormone secretion rapidly ceases. Low-dose
      vasopressin increases systemic blood pressure and decreases the need for
      catecholamines in brain-dead organ donors but it is not available in many
      countries. Terlipressin is a synthetic analog of vasopressin characterized by
      greater selectivity for the V1 receptor than vasopressin. To date, the efficacy
      of terlipressin as a pressor agent in humans has been reported in a few studies.
      METHOD: Pharmacology and literature about the use of terlipressin in shock and in
      particularly in neurogenic shock following brain death is summarized and our
      personal experience is reported. RESULTS AND CONCLUSION: Terlipressin is helpful
      in controlling severe hypotension; its use allowed to reduce the infusion rate of
      norepinephrine about 50% in two of three brain-death organ donors, but there are
      not yet enough data to define its therapeutic range and incidence of collateral
      effects on the grafts.

PMID- 23121214
TI  - Regulation of acetylcholinesterase activity by nitric oxide in rat neuromuscular
      junction via N-methyl-D-aspartate receptor activation.
AB  - Acetylcholinesterase (AChE) is an enzyme that hydrolyses the neurotransmitter
      acetylcholine, thereby limiting spillover and duration of action. This study
      demonstrates the existence of an endogenous mechanism for the regulation of
      synaptic AChE activity. At the rat extensor digitorum longus neuromuscular
      junction, activation of N-methyl-d-aspartate (NMDA) receptors by combined
      application of glutamate and glycine led to enhancement of nitric oxide (NO)
      production, resulting in partial AChE inhibition. Partial AChE inhibition was
      measured using increases in miniature endplate current amplitude. AChE inhibition
      by paraoxon, inactivation of NO synthase by N(x)-nitro-L-arginine methyl ester,
      and NMDA receptor blockade by DL-2-amino-5-phosphopentanoic acid prevented the
      increase in miniature endplate current amplitude caused by amino acids. High
      frequency (10 Hz) motor nerve stimulation in a glycine-containing bathing
      solution also resulted in an increase in the amplitude of miniature endplate
      currents recorded during the interstimulus intervals. Pretreatment with an NO
      synthase inhibitor and NMDA receptor blockade fully eliminated this effect. This
      suggests that endogenous glutamate, released into the synaptic cleft as a co
      mediator of acetylcholine, is capable of triggering the NMDA receptor/NO synthase
      mediated pathway that modulates synaptic AChE activity. Therefore, in addition to
      well-established modes of synaptic plasticity (e.g. changes in the effectiveness
      of neurotransmitter release and/or the sensitivity of the postsynaptic membrane),
      another mechanism exists based on the prompt regulation of AChE activity.

PMID- 23121215
TI  - Down-regulation of PvTRE1 enhances nodule biomass and bacteroid number in the
      common bean.
AB  - Legume-rhizobium interactions have been widely studied and characterized, and the
      disaccharide trehalose has been commonly detected during this symbiotic
      interaction. It has been proposed that trehalose content in nodules during this
      symbiotic interaction might be regulated by trehalase. In the present study, we
      assessed the role of trehalose accumulation by down-regulating trehalase in the
      nodules of common bean plants. We performed gene expression analysis for
      trehalase (PvTRE1) during nodule development. PvTRE1 was knocked down by RNA
      interference (RNAi) in transgenic nodules of the common bean. PvTRE1 expression
      in nodulated roots is mainly restricted to nodules. Down-regulation of PvTRE1 led
      to increased trehalose content (78%) and bacteroid number (almost one order of
      magnitude). In addition, nodule biomass, nitrogenase activity, and GOGAT
      transcript accumulation were significantly enhanced too. The trehalose
      accumulation, triggered by PvTRE1 down-regulation, led to a positive impact on
      the legume-rhizobium symbiotic interaction. This could contribute to the
      agronomical enhancement of symbiotic nitrogen fixation.

PMID- 23121216
TI  - Harm reduction and abortion.

PMID- 23121217
TI  - Dioxetane-doped silica nanoparticles as ultrasensitive reagentless
      thermochemiluminescent labels for bioanalytics.
AB  - Thermochemiluminescence (TCL; the light emission originating by the thermally
      triggered decomposition of a molecule) was proposed in the late 1980s as a
      detection technique for immunoassays. However, after little pioneering work, this
      technique was abandoned because of the high temperatures required and the poor
      detectability in comparison to other labels. Here we describe for the first time
      a thermochemiluminescent acridine-based 1,2-dioxetane with a remarkably low
      (i.e., below 100  degrees C) emission-triggering temperature, which made it
      possible to obtain light emission even in an aqueous environment, as well as
      amino-functionalized silica nanoparticles loaded with this compound and the
      fluorescent energy acceptor dipyridamole. Thanks to the signal amplification due
      to the large number of 1,2-dioxetane molecules in each nanoparticle (about 10(4))
      and the increased emission efficiency due to energy transfer to the fluorescent
      acceptor, the doped nanoparticles could be revealed with a detectability close to
      that of chemiluminescent enzyme labels (the limit of detection of doped
      nanoparticles by TCL imaging was 1 * 10(-16) mol mm(-2), thus approaching the
      value of 5 * 10(-17) mol mm(-2) obtained for the enzyme label horseradish
      peroxidase with chemiluminescence detection). They could thus be used as highly
      detectable labels in the development of sensitive TCL-based immunoassays and
      nucleic acid hybridization assays, in which the detection step does not require
      any additional chemical reagent. We believe that these doped silica nanoparticles
      could pave the way for the revival of TCL detection in bioanalytics, taking
      advantage of the reagentless detection and the high signal/noise ratio in
      comparison with conventional luminescence detection techniques.

PMID- 23121218
TI  - Potential antagonistic effects of nine natural fatty acids against Meloidogyne
      incognita.
AB  - Fatty acids, the essential components of life, were widely present in various
      seed cakes, gutter oil, and other resources. The objective of this study was to
      evaluate the potential antagonistic effects of nine fatty acids (FAs) against
      Meloidogyne incognita (root-knot nematodes). The results showed that butyric,
      caprylic, capric, lauric, myristic, palmitic, and oleic acids significantly
      reduced M. incognita reproduction, whereas cucumber (Cucumus sativus) biomass was
      not adversely affected by the tested FAs and was even significantly increased in
      several fatty acids treatments. All nine tested fatty acids showed apparent
      inhibitory effects on egg hatching on day 21, especially capric acid with which
      the hatching rate was reduced to 15.8% as compared to that using sterile
      distilled water. Caproic, caprylic, capric, lauric, myristic, and palmitic acids
      caused significantly higher mortality of the second-stage juvenile of M.
      incognita than the other three FAs, and both caprylic and capric acids resulted
      in approximately 50% mortality (2000 MUmol/L) after a 24 h exposure. In
      conclusion, fatty acids showed the nematicidal effect differently, among which
      capric acid showed a strong nematicidal effect and might be a powerful active
      substance for integrated M. incognita management. Given the general nematicidal
      properties of FAs, farmers might utilize waste resources, such as oil seed cake,
      gutter oil, etc., containing various FAs or use pure FAs for effective M.
      incognita management.

PMID- 23121219
TI  - Laparo-endoscopic single-site (LESS) bilateral nephroureterectomy for patients
      with end-stage renal disease.
AB  - We present the first report of LESS bilateral nephroureterectomy via the
      transperitoneal approach using the home-made single port. Two patients received
      LESS bilateral nephroureterectomies and bladder cuffs resection with homemade
      single ports, which were created by using an Alexis wound retractor as an access
      platform through a 4 cm incision. Distal ureters were resected through the same
      incision with Endo-loop. No additional ports were used and both procedures were
      completed successfully without traditional laparoscopic/open conversion or
      complication. LESS nephreoureterectomy with bladder cuff excision was performed
      in 460 and 635 minutes with an estimated blood loss of 50 and 400 mL,
      respectively. Patients were discharged on postoperative day 3 and 7,
      respectively. Our report demonstrates that LESS bilateral nephroureterectomy and
      bladder cuff resection is a safe and feasible procedure for urothelial carcinoma
      of upper urinary tract in patients at dialysis.

PMID- 23121220
TI  - Multimerizable HIV Gag derivative binds to the liquid-disordered phase in model
      membranes.
AB  - During HIV assembly, a protein coat on the inner leaflet of the plasma membrane
      drives the formation of virus particles, and appears to induce the preferential
      accumulation of 'raft' lipids in the viral envelope, although the lipid raft
      concept mainly proposes microdomains of these lipids in the outer leaflet. The
      common hypothesis is that Gag preferentially associates with, and thereby
      probably induces, raft-like domains, because the protein is multimerized and
      specifically linked to two saturated acyl chains. To test this hypothesis, we
      constructed a minimal in vitro system in which we analysed the interaction of a
      Gag derivative, which could be triggered to multimerize, with a domain-forming
      model membrane resembling the inner leaflet of the plasma membrane. Confirming
      studies with authentic Gag, this Gag derivative only bound to membranes when it
      was multimerized, myristoylated and when phosphatidylinositol 4,5-bisphosphate
      was present in the membrane. Unexpectedly, however, the multimerized Gag
      derivative was largely excluded from ordered domains in model membranes. This
      suggests that the mechanism of membrane reorganization during HIV assembly does
      not simply result from a higher affinity of the clustered Gag membrane binding
      domain to ordered membrane domains, but involves more complex biophysical
      interactions or possibly also an additional protein machinery.

PMID- 23121222
TI  - Clinical responses to antidepressants among 1036 acutely depressed patients with
      bipolar or unipolar major affective disorders.
AB  - OBJECTIVE: Whether responses to antidepressants differ in bipolar and unipolar
      depression remains unresolved. METHOD: We analyzed patient characteristics and
      outcomes of antidepressant treatment of 1036 depressed patients with bipolar-I or
      bipolar-II disorder, or unipolar major depression, using bivariate and
      multivariate methods and survival analysis, testing the hypothesis that responses
      would be superior in unipolar depression. RESULTS: Antidepressants were given to
      84.8% (878/1036) of depressed patients: 58.9% of 93 bipolar-I, 80.1% of 117
      bipolar-II, and 91.3% of 668 unipolar disorder cases. The 158 not given
      antidepressants had more manias/year, spent more months in mania and depression,
      and were far more likely to receive mood stabilizers or antipsychotics long term.
      Improvement of HDRS21 depression ratings ranked: bipolar-II (69.6%) > bipolar-I
      (62.9%) > unipolar (57.9%; P < 0.0001), independent of initial illness severity.
      Responder rates (>=50% improved without switching) ranked: bipolar-II (77.0%) >
      bipolar-I (71.6%) > unipolar (61.7%; P < 0.0001). Remission rates (final HDRS <
      7) ranked: 54.0%, 50.6%, and 40.8% respectively (P = 0.02); 67.5% remitted within
      12 weeks of treatment. Survival-computed median time to remission (15.0 weeks,
      overall) was shortest for bipolar-II patients (10.7 weeks). The 3-month risk of
      switching into mania-hypomania ranked: bipolar-II (15.8%) > bipolar-I (8.60%) >
      unipolar (0.56%). Multivariate modeling found bipolar diagnosis, shorter latency
      to remission, more recent trial year, and fewer weeks depressed before treatment
      to be associated with greater percent improvement of HDRS ratings. CONCLUSION:
      Selective use of antidepressants with or without mood stabilizers in non
      agitated, depressed bipolar disorder patients for short periods was effective
      with moderate risk of potentially dangerous, manic mood elevation.

PMID- 23121221
TI  - Genetic characterization and transmitted drug resistance of the HIV type 1
      epidemic in men who have sex with men in Beijing, China.
AB  - A rapid increase in the number of HIV cases in the men who have sex with men
      (MSM) population has been observed in China; however, little information is
      available on the genetic characterization of HIV prevalent in this population. In
      this study, 95 HIV-1-seropositive drug-naive patients from the Beijing MSM
      population were enrolled. The genetic characterization and transmission of drug
      resistance of HIV-1 were examined based on full-length gag, pol, and partial env
      gene sequences. Three subtypes, including CRF01_AE (56.0%), B (30.8%), and
      CRF07_BC (12.6%), were identified. Close phylogenetic relationships were found
      among these strains with isolates from other populations in Beijing and MSM
      isolates from Hebei province, which suggested that the Beijing MSM population
      might act as a bridge for HIV transmission between MSM and other high-risk
      populations. Drug-resistant mutations were identified in 5.3% of sampled
      individuals. Our results provided detailed genetic data and would be helpful for
      understanding the transmitting pattern of HIV strains between MSM and other
      populations.

PMID- 23121223
TI  - Loss of gallbladder interstitial Cajal-like cells in patients with
      cholelithiasis.
AB  - BACKGROUND: Interstitial cells of Cajal (ICCs) play an important role in the
      regulation of gut motility. There is growing evidence that interstitial Cajal
      like cells (ICLCs) are present in the gallbladder wall. We hypothesize that
      changes in the density of ICLCs in the gallbladder wall may lead to the
      development of cholelithiasis due to the impairment of the gallbladder motility.
      The purpose of this study was to identify ICLCs in the gallbladders of patients
      with gallstones and to assess their densities. METHODS: Data from 30 patients
      with gallstones and 25 individuals without gallstones were compared. Tissue
      samples were obtained during surgery, embedded in paraffin, and cut into
      sections. Following staining for CD117 and mast cell tryptase, the number of
      ICLCs and mast cells was determined using image analysis. KEY RESULTS: Cells
      positive for the c-Kit receptor (CD117) were detected in the gallbladder wall in
      all cases examined. Interstitial Cajal-like cells were most frequently observed
      in the muscularis propria. The density of ICLCs in the muscularis propria was
      significantly lower in the patients with gallstones than the density observed in
      the controls (26.24 +/- 10.89 vs 56.29 +/- 13.35 cells/mm(2)). In contrast, the
      number of mast cells in the gallbladder was increased in the patients with
      gallstones when compared with the controls (143 +/- 24 vs 112 +/- 19
      cells/mm(2)). CONCLUSIONS & INFERENCES: The histopathological differences
      observed in this study may help elucidate the pathophysiology of gallstones.
      Gallbladder motility may be affected by the decreased number of ICLCs in patients
      with cholelithiasis.

PMID- 23121224
TI  - Genomic conflict drives patterns of X-linked population structure in Drosophila
      neotestacea.
AB  - Intragenomic conflict has the potential to cause widespread changes in patterns
      of genetic diversity and genome evolution. In this study, we investigate the
      consequences of sex-ratio (SR) drive on the population genetic patterns of the X
      chromosome in Drosophila neotestacea. An SR X-chromosome prevents the maturation
      of Y-bearing sperm during male spermatogenesis and thus is transmitted to ~100%
      of the offspring, nearly all of which are daughters. Selection on the rest of the
      genome to suppress SR can be strong, and the resulting conflict over the
      offspring sex ratio can result in the accumulation of multiple loci on the X
      chromosome that are necessary for the expression of drive. We surveyed variation
      at 12 random X-linked microsatellites across 16 populations of D. neotestacea
      that range in SR frequency from 0% to 30%. First, every locus was differentiated
      between SR and wild-type chromosomes, and this drives genetic structure at the X
      chromosome. Once the association with SR is accounted for, the patterns of
      differentiation among populations are similar to the autosomes. Second, within
      wild-type chromosomes, the relative heterozygosity is reduced in populations with
      an increased prevalence of drive, and the heterozygosity of SR chromosomes is
      higher than expected based on its prevalence. The combination of the relatively
      high prevalence of SR drive and the structuring of polymorphism between the SR
      and wild-type chromosomes suggests that genetic conflict because of SR drive has
      had significant consequences on the patterns of X-linked polymorphism and thus
      also probably affects the tempo of X-chromosome evolution in D. neotestacea.

PMID- 23121225
TI  - Differing relationship outcomes when sex happens before, on, or after first
      dates.
AB  - While recent studies have suggested that the timing of sexual initiation within a
      couple's romantic relationship has important associations with later relationship
      success, few studies have examined how such timing is associated with
      relationship quality among unmarried couples. Using a sample of 10,932
      individuals in unmarried, romantic relationships, we examined how four sexual
      timing patterns (i.e., having sex prior to dating, initiating sex on the first
      date or shortly after, having sex after a few weeks of dating, and sexual
      abstinence) were associated with relationship satisfaction, stability, and
      communication in dating relationships. Results suggested that waiting to initiate
      sexual intimacy in unmarried relationships was generally associated with positive
      outcomes. This effect was strongly moderated by relationship length, with
      individuals who reported early sexual initiation reporting increasingly lower
      outcomes in relationships of longer than two years. 

PMID- 23121226
TI  - Acquired auditory agnosia in childhood and normal sleep electroencephalography
      subsequently diagnosed as Landau-Kleffner syndrome: a report of three cases.
AB  - AIM:   We report three cases of Landau-Kleffner syndrome (LKS) in children (two
      females, one male) in whom diagnosis was delayed because the sleep
      electroencephalography (EEG) was initially normal. METHOD:   Case histories
      including EEG, positron emission tomography findings, and long-term outcome were
      reviewed. RESULTS:   Auditory agnosia occurred between the age of 2 years and 3
      years 6 months, after a period of normal language development. Initial awake and
      sleep EEG, recorded weeks to months after the onset of language regression,
      during a nap period in two cases and during a full night of sleep in the third
      case, was normal. Repeat EEG between 2 months and 2 years later showed
      epileptiform discharges during wakefulness and strongly activated by sleep, with
      a pattern of continuous spike-waves during slow-wave sleep in two patients.
      Patients were diagnosed with LKS and treated with various antiepileptic regimens,
      including corticosteroids. One patient in whom EEG became normal on
      hydrocortisone is making significant recovery. The other two patients did not
      exhibit a sustained response to treatment and remained severely impaired.
      INTERPRETATION:   Sleep EEG may be normal in the early phase of acquired auditory
      agnosia. EEG should be repeated frequently in individuals in whom a firm clinical
      diagnosis is made to facilitate early treatment.

PMID- 23121227
TI  - The natural history of eosinophilic oesophagitis in the transition from childhood
      to adulthood.
AB  - BACKGROUND: Eosinophilic oesophagitis (EoE) is a chronic inflammatory condition
      affecting both children and adults. Little is known about the natural history of
      EoE in the transition from childhood into adulthood. AIM: To determine the
      prevalence of EoE symptoms and impact of EoE on quality of life among adults
      diagnosed with EoE during childhood. METHODS: This is a cross-sectional study of
      EoE patients from the Children's Hospital of Philadelphia EoE registry. Patients
      >=18 years diagnosed with EoE during childhood were administered validated
      dysphagia [Mayo Dysphagia Questionnaire (MDQ)-30] and Quality of Life (PAGI-QOL)
      questionnaires. Ongoing EoE treatments were ascertained. RESULTS: A total of 140
      EoE patients >=18 years were identified; 53 completed all questions. Only 6 (11%)
      subjects had positive (n = 2) or indeterminate (n = 4) dysphagia scores. However,
      of 47 patients with negative scores, 18 (37%) reported ongoing difficulty
      swallowing. The mean PAGI-QOL score was 4.58/5. The dietary dimension score was
      3.73/5. Current pharmacological EoE treatments were topical steroids (3/53) and
      interleukin-5 antagonists (3/53). Additionally, 26/53 (49%) were on PPI therapy
      and 40/53 (76%) were following allergy directed diets. CONCLUSIONS: The majority
      of young adults diagnosed with EoE during childhood continue to require
      pharmacological treatment and/or dietary modification for EoE. A substantial
      proportion of this population experiences ongoing swallowing difficulties that a
      standard dysphagia questionnaire fails to capture. Dietary quality of life, but
      not total quality of life, appears to be adversely affected. These data suggest
      that EoE diagnosed during childhood remains a significant medical issue during
      early adulthood, and that better EoE symptom measurement instruments are needed.

PMID- 23121228
TI  - Doing what we imagine: completion rates and frequency attributes of imagined
      future events one year after prospection.
AB  - Recent years have seen an explosion of studies examining behavioural and neural
      aspects of imagining future events. However, little is known about whether
      imagined future events reflect future happenings. We examined event occurrence 1
      year after participants imagined highly probable future events, specific to place
      and time. Overall, participants did engage in most of their imagined events.
      Completion rates were similar to naturalistic prospective memory and
      implementation intention studies examining personal plan completion.
      Approximately 20% of events were abandoned. We found participants often imagined
      events that were repeated many times in the course of a year and this impacted
      the vividness of recollection, sense of personal importance, personal involvement
      in event fulfilment, and extent of positive emotionality 1 year later. Together,
      the results provide an important validation for prospection research and
      highlight novel dimensions in the temporal structure of future-thinking.

PMID- 23121229
TI  - Effects of intra-aortic balloon pump timing on baroreflex activities in a closed
      loop cardiovascular hybrid model.
AB  - Despite 50 years of research to assess the intra-aortic balloon pump (IABP)
      effects on patients' hemodynamics, some issues related to the effects of this
      therapy are still not fully understood. One of these issues is the effect of
      IABP, its inflation timing and duration on peripheral circulation autonomic
      controls. This work provides a systematic analysis of IABP effects on baroreflex
      using a cardiovascular hybrid model, which consists of computational and
      hydraulic submodels. The work also included a baroreflex computational model that
      was connected to a hydraulic model with a 40-cm(3) balloon. The IABP was operated
      at different inflation trigger timings (-0.14 to 0.31 s) and inflation durations
      (0.05-0.45 s), with time of the dicrotic notch being taken as t = 0. Baroreflex
      dependent parameters-afferent and efferent pathway activity, heart rate,
      peripheral resistance, and venous tone-were evaluated at each of the inflation
      trigger times and durations considered. Balloon early inflation (0.09 s before
      the dicrotic notch) with inflation duration of 0.25 s generated a maximum net
      increment of afferent pathway activity of 10%, thus leading to a decrement of
      efferent sympathetic activity by 15.3% compared with baseline values. These times
      also resulted in a reduction in peripheral resistance and heart rate by 4 and
      4.3% compared with baseline value. We conclude that optimum IABP triggering time
      results in positive effects on peripheral circulation autonomic controls.
      Conversely, if the balloon is not properly timed, peripheral resistance and heart
      rate may even increase, which could lead to detrimental outcomes.

PMID- 23121230
TI  - Eruptive keratoacanthomas after Jessners and trichloroacetic acid peel for
      actinic keratosis.

PMID- 23121231
TI  - An analysis of the implant-supported overdenture in the edentulous mandible.
AB  - This investigation examined the cumulative survival rate of the implant-supported
      overdenture using two types of attachments in patients treated at Show Chwan
      Memorial Hospital Implant Center from 1992 to 2006. Fifty-one patients (30 men
      and 21 women) were treated with mandibular implant-supported overdentures.
      Attachment systems used were the Hader bar with bilateral, cast ERA attachments
      (Group A, 31 patients with 15 men and 16 women, 134 implants) and the Hader bar
      with bilateral, distal extension cantilevers (Group B, 20 patients with 15 men
      and 5 women, 85 implants). Two hundred and four implants remained at the end of
      the follow-up period. Among failed implants, 10 implants were in Group A (failure
      rate: 10/134 = 7.5%), whereas five implants were in Group B (failure rate: 5/85 =
      5.9%). Sixty-six point seven per cent (10/15) of failed implants were placed in
      the distal anterior mandible, and 33.3% (5/15) were placed in the middle anterior
      mandible. Survival was also examined with respect to condition of the opposing
      arch. Patients wearing a maxillary removable partial denture had the highest
      implant failure rate (5/51 = 9.8%), whereas the failure rate of the maxillary
      complete denture group was only 5.7%. The most frequent need for maintenance was
      wear over patrix component of ERA or Hader clip (n = 56). Eight patients
      experienced connector fracture between ERA and Hader bar, and one experienced
      distal extension cantilever fracture. The implant-supported overdenture can be an
      effective and reliable alternative to the conventional complete mandibular
      denture. Fewer prosthetic complications were seen in overdentures retained with
      distal extension cantilever attachments.

PMID- 23121232
TI  - Do wild fish species contribute to the transmission of koi herpesvirus to carp in
      hatchery ponds?
AB  - The koi herpesvirus (KHV) has spread worldwide since its discovery in 1998 and
      causes disease and mortality in koi and common carp populations with a high
      impact on the carp production industry. Many investigations have been conducted
      to examine ways of distribution and to identify possible transmission vectors.
      The answers, however, raise many new questions. In the present study, different
      wild fish species taken from carp ponds with a history of KHV infection were
      examined for their susceptibility to the virus. In the tissue of these fish, the
      virus load was determined and it was tested whether a release of the virus could
      be induced by stress and the virus then could be transferred to naive carp. Wild
      fish were gathered from carp ponds during acute outbreaks of virus-induced
      mortality in summer and from ponds stocked with carp carrying a latent KHV
      infection. From these ponds, wild fish were collected during the harvesting
      process in autumn or spring when the ponds were drained. We found that regardless
      of season, temperature variation, age and infection status of the carp stock,
      wild fish from carp ponds and its outlets could be tested positive for the KHV
      genome using real-time PCR with a low prevalence and virus load. Furthermore,
      virus transfer to naive carp was observed after a period of cohabitation.
      Cyprinid and non-cyprinid wild fish can therefore be considered as an
      epidemiological risk for pond carp farms.

PMID- 23121233
TI  - Stratum basale keratinocyte expression of the cell-surface glycoprotein CDCP1
      during epidermogenesis and its role in keratinocyte migration.
AB  - BACKGROUND: Epidermogenesis and epidermal wound healing are tightly regulated
      processes during which keratinocytes must migrate, proliferate and differentiate.
      Cell-to-cell adhesion is crucial to the initiation and regulation of these
      processes. CUB-domain-containing protein (CDCP)1 is a transmembrane glycoprotein
      that is differentially tyrosine phosphorylated during changes in cell adhesion
      and survival signalling, and is expressed by keratinocytes in native human skin,
      as well as in primary cultures. OBJECTIVES: To investigate the expression of
      CDCP1 during epidermogenesis and its role in keratinocyte migration. METHODS: We
      examined both human skin tissue and an in vitro three-dimensional human skin
      equivalent model to examine the expression of CDCP1 during epidermogenesis. To
      examine the role of CDCP1 in keratinocyte migration we used a function-blocking
      anti-CDCP1 antibody and a real-time TranswellTM cell migration assay. RESULTS:
      Immunohistochemical analysis indicated that in native human skin CDCP1 is
      expressed in the stratum basale and stratum spinosum. In contrast, during
      epidermogenesis in a three-dimensional human skin equivalent model, CDCP1 was
      expressed only in the stratum basale, with localization restricted to the cell
      cell membrane. No expression was detected in basal keratinocytes that were in
      contact with the basement membrane. Furthermore, an anti-CDCP1 function-blocking
      antibody was shown to disrupt keratinocyte chemotactic migration in vitro.
      CONCLUSIONS: These findings delineate the expression of CDCP1 in human epidermal
      keratinocytes during epidermogenesis and demonstrate that CDCP1 is involved in
      keratinocyte migration.

PMID- 23121234
TI  - Identifying women with undetected ovarian cancer: independent and external
      validation of QCancer((r)) (Ovarian) prediction model.
AB  - Early identification of ovarian cancer is an unresolved challenge and the
      predictive value of single symptoms is limited. We evaluated the performance of
      QCancer((r)) (Ovarian) prediction model for predicting the risk of ovarian cancer
      in a UK cohort of general practice patients. A total of 1.1 million patients
      registered with a general practice surgery between 1 January 2000 and 30 June
      2008, aged 30-84 years with 735 ovarian cancer cases, were included in the
      analysis. Ovarian cancer was defined as incident diagnosis of ovarian cancer
      during the 2 years after study entry. The results from this independent and
      external validation of QCancer((r)) (Ovarian) prediction model demonstrated good
      performance on a large cohort of general practice patients. QCancer((r))
      (Ovarian) had very good discrimination with an area under the receiver operating
      characteristic curve of 0.86 and explained 59.9% of the variation. QCancer((r))
      (Ovarian) was well calibrated across all tenths of risk and over all age. The 10%
      of women with the highest predicted risks included 64% of all ovarian cancer
      diagnoses over the next 2 years. QCancer((r)) (Ovarian) appears to be a useful
      tool for identifying undetected cases of ovarian cancer in primary care in the UK
      for early referral and investigation.

PMID- 23121235
TI  - Thermoresponsive cell culture substrates based on PNIPAM brushes functionalized
      with adhesion peptides: theoretical considerations of mechanism and design.
AB  - Thermoresponsive tissue culture substrates based on PNIPAM brushes are used to
      harvest confluent cell sheets for tissue engineering. The prospect of clinical
      use imposes the utilization of culture medium free of bovine serum, thus
      suggesting conjugation with adhesion peptides containing the RGD minimal
      recognition sequence. The optimum position of the RGD along the chain should
      ensure both cell adhesion at 37  degrees C and cell detachment at T(L) below the
      lower critical solution temperature of PNIPAM. Design guidelines are formulated
      from considerations of brush confinement by the cells: (i) Cell adhesion at 37 
      degrees C is controlled by the RGDs accessible without brush compression. (ii)
      Cell detachment at T(L) is driven by a disjoining force due to confinement of the
      swollen brush by cells retaining integrin-RGD bonds formed at 37  degrees C.
      These suggest placing the RGDs at the grafting surface or its vicinity. Randomly
      placed RGDs do not enable efficient detachment because a large fraction of the
      integrin-RGD bonds are not sufficiently tensioned at T(L), in line with
      experimental observations (Ebara, M.; Yamato, M.; Aoyagi, T.; Kikuchi, A.; Sakai,
      K.; Okano, T. Immobilization of celladhesive peptides to temperature-responsive
      surfaces facilitates both serum-free cell adhesion and noninvasive cell harvest.
      Tissue Eng. 2004, 10, 1125-1135). The theory framework enables analysis of
      culture media based on polymer brushes conjugated with adhesion peptides in
      general.

PMID- 23121236
TI  - The emerging role of miR-208a in the heart.
AB  - MicroRNAs (miRNAs) are a class of regulatory small RNAs that have fundamentally
      transformed our understanding of how gene networks are regulated representing one
      of the most exciting areas of the modern cardiology research. Among all known
      miRNAs, miR-208a is one of the most important heart-enriched miRNA playing a
      crucial role in the heart health and disease. miR-208a is a member of a miRNA
      family that also included miR-208b and is encoded by an intronic region of the
      Myh6 gene. Within the heart, miR-208a and miR-208b are involved in the regulation
      of the myosin heavy chain isoformswitch during development and in
      pathophysiological conditions. miR-208a is sufficient to induce arrhythmias,
      cardiac remodeling, and to regulate the expression of hypertrophy pathway
      components and the cardiac conduction system. Recently, the identification of miR
      208a in the bloodstream has led to a great clinical interest to use this molecule
      as a potential noninvasive biomarker of myocardial injuries.

PMID- 23121241
TI  - A perceptual discrimination task results in greater facilitation of voluntary
      saccades in Parkinson's disease patients.
AB  - Many studies have shown that Parkinson's disease (PD) affects not only the
      ability to generate voluntary saccades but also the ability to suppress reflexive
      saccades (hyper-reflexivity). To further investigate these apparently
      contradictory effects of PD on the saccade system we adapted a well-known dual
      task paradigm (Deubel, 2008) to measure saccades with and without a peripheral
      discrimination task. Previously we reported that the concurrent performance of a
      perceptual discrimination task abnormally reduced the latencies of reflexive
      saccades in PD. Here we report the effects of the concurrent discrimination task
      on the generation of voluntary saccades in a PD and a control group. As expected,
      when saccades were performed without the discrimination task the PD group made
      voluntary saccades with longer latencies and smaller gain than the control group.
      The concurrent performance of the perceptual discrimination task facilitated the
      initiation of voluntary saccades in both groups, but, surprisingly, this
      facilitatory effect was stronger in the PD group than in the control group. In
      addition, in the PD group voluntary saccades were abnormally facilitated by the
      peripheral symbol-changes that occur during saccade planning in this paradigm.
      The results of this study may help to clarify apparently contradictory oculomotor
      abnormalities observed in PD.

PMID- 23121242
TI  - Epigenetic variation creates potential for evolution of plant phenotypic
      plasticity.
AB  - Heritable variation in plant phenotypes, and thus potential for evolutionary
      change, can in principle not only be caused by variation in DNA sequence, but
      also by underlying epigenetic variation. However, the potential scope of such
      phenotypic effects and their evolutionary significance are largely unexplored.
      Here, we conducted a glasshouse experiment in which we tested the response of a
      large number of epigenetic recombinant inbred lines (epiRILs) of Arabidopsis
      thaliana--lines that are nearly isogenic but highly variable at the level of DNA
      methylation--to drought and increased nutrient conditions. We found significant
      heritable variation among epiRILs both in the means of several ecologically
      important plant traits and in their plasticities to drought and nutrients.
      Significant selection gradients, that is, fitness correlations, of several mean
      traits and plasticities suggest that selection could act on this epigenetically
      based phenotypic variation. Our study provides evidence that variation in DNA
      methylation can cause substantial heritable variation of ecologically important
      plant traits, including root allocation, drought tolerance and nutrient
      plasticity, and that rapid evolution based on epigenetic variation alone should
      thus be possible.

PMID- 23121243
TI  - Nanoscale electrochemistry.

PMID- 23121244
TI  - Micro- to nanostructure and geochemistry of extant crinoidal echinoderm
      skeletons.
AB  - This paper reports the results of micro- to nanostructural and geochemical
      analyses of calcitic skeletons from extant deep-sea stalked crinoids. Fine-scale
      (SEM, FESEM, AFM) observations show that the crinoid skeleton is composed of
      carbonate nanograins, about 20-100 nm in diameter, which are partly separated by
      what appears to be a few nm thick organic layers. Sub-micrometre-scale
      geochemical mapping of crinoid ossicles using a NanoSIMS ion microprobe, combined
      with synchrotron high-spatial-resolution X-ray micro-fluorescence (MU-XRF) maps
      and X-ray absorption near-edge structure spectroscopy (XANES) show that high Mg
      concentration in the central region of the stereom bars correlates with the
      distribution of S-sulphate, which is often associated with sulphated
      polysaccharides in biocarbonates. These data are consistent with
      biomineralization models suggesting a close association between organic
      components (including sulphated polysaccharides) and Mg ions. Additionally,
      geochemical analyses (NanoSIMS, energy dispersive spectroscopy) reveal that
      significant variations in Mg occur at many levels: within a single stereom
      trabecula, within a single ossicle and within a skeleton of a single animal.
      Together, these data suggest that physiological factors play an important role in
      controlling Mg content in crinoid skeletons and that great care should be taken
      when using their skeletons to reconstruct, for example, palaeotemperatures and
      Mg/Ca palaeo-variations of the ocean.

PMID- 23121245
TI  - Lipoarabinomannan mannose caps do not affect mycobacterial virulence or the
      induction of protective immunity in experimental animal models of infection and
      have minimal impact on in vitro inflammatory responses.
AB  - Mannose-capped lipoarabinomannan (ManLAM) is considered an important virulence
      factor of Mycobacterium tuberculosis. However, while mannose caps have been
      reported to be responsible for various immunosuppressive activities of ManLAM
      observed in vitro, there is conflicting evidence about their contribution to
      mycobacterial virulence in vivo. Therefore, we used Mycobacterium bovis BCG and
      M. tuberculosis mutants that lack the mannose cap of LAM to assess the role of
      ManLAM in the interaction of mycobacteria with the host cells, to evaluate
      vaccine-induced protection and to determine its importance in M. tuberculosis
      virulence. Deletion of the mannose cap did not affect BCG survival and
      replication in macrophages, although the capless mutant induced a somewhat higher
      production of TNF. In dendritic cells, the capless mutant was able to induce the
      upregulation of co-stimulatory molecules and the only difference we detected was
      the secretion of slightly higher amounts of IL-10 as compared to the wild type
      strain. In mice, capless BCG survived equally well and induced an immune response
      similar to the parental strain. Furthermore, the efficacy of vaccination against
      a M. tuberculosis challenge in low-dose aerosol infection models in mice and
      guinea pigs was not affected by the absence of the mannose caps in the BCG.
      Finally, the lack of the mannose cap in M. tuberculosis did not affect its
      virulence in mice nor its interaction with macrophages in vitro. Thus, these
      results do not support a major role for the mannose caps of LAM in determining
      mycobacterial virulence and immunogenicity in vivo in experimental animal models
      of infection, possibly because of redundancy of function.

PMID- 23121246
TI  - Be FAIR to students: four principles that lead to more effective learning.
AB  - A teacher is a professional not a technician. An understanding of some basic
      principles about learning can inform the teacher or trainer in their day-to-day
      practice as a teacher or a trainer. The FAIR principles are: provide feedback to
      the student, engage the student in active learning, individualise the learning to
      the personal needs of the student and make the learning relevant. Application of
      the principles can lead to more effective learning - the poor teacher can become
      a good teacher and the good teacher an excellent teacher.

PMID- 23121247
TI  - Simulation in healthcare: a taxonomy and a conceptual framework for instructional
      design and media selection.
AB  - BACKGROUND: Simulation in healthcare lacks a dedicated framework and supporting
      taxonomy for instructional design (ID) to assist educators in creating
      appropriate simulation learning experiences. AIMS: This article aims to fill the
      identified gap. It provides a conceptual framework for ID of healthcare
      simulation. METHODS: The work is based on published literature and authors'
      experience with simulation-based education. RESULTS: The framework for ID itself
      presents four progressive levels describing the educational intervention. Medium
      is the mode of delivery of instruction. Simulation modality is the broad
      description of the simulation experience and includes four modalities (computer
      based simulation, simulated patient (SP), simulated clinical immersion, and
      procedural simulation) in addition to mixed, hybrid simulations. Instructional
      method describes the techniques used for learning. Presentation describes the
      detailed characteristics of the intervention. The choice of simulation as a
      learning medium is based on a matrix of simulation relating acuity (severity) to
      opportunity (frequency) of events, with a corresponding zone of simulation. An
      accompanying chart assists in the selection of appropriate media and simulation
      modalities based on learning outcomes. CONCLUSION: This framework should help
      educators incorporate simulation in their ID efforts. It also provides a taxonomy
      to streamline future research and ID efforts in simulation.

PMID- 23121248
TI  - How we put into practice the principles of embedding medical students into
      healthcare teams.
AB  - To learn the practice of medicine, one must practice medicine. To maximize
      opportunities for practice, medical students are often embedded into functioning
      healthcare teams. At the National University of Singapore, students are
      distributed for clinical training at a variety of sites across the country. To
      enhance consistency of experience, the principles of embedding were clarified by
      a consensus-driven process and implemented according to local context. The
      principles are that embedding is safe for students and patients, independent
      thought, and commitment are required, students add value to the team, and that
      timely meaningful feedback is given. During the implementation phase, many
      lessons were distilled to further improve the process of student embedding.

PMID- 23121249
TI  - Influence of episodes of intermittent viremia ("blips") on immune responses and
      viral load rebound in successfully treated HIV-infected patients.
AB  - Presenting episodes of intermittent viremia (EIV) under combination
      antiretroviral therapy (cART) is frequent, but there exists some controversy
      about their consequences. They have been described as inducing changes in immune
      responses potentially associated with a better control of HIV infection.
      Conversely, it has been suggested that EIV increases the risk of virological
      failure. A retrospective analysis of a prospective, randomized double-blinded
      placebo-controlled study was performed. Twenty-six successfully treated HIV
      infected adults were randomized to receive an immunization schedule or placebo,
      and after 1 year of follow-up cART was discontinued. The influence of EIV on T
      cell subsets, HIV-1-specific T cell immune responses, and viral load rebound, and
      the risk of developing genotypic mutations were evaluated, taking into account
      the immunization received. Patients with EIV above 200 copies/ml under cART had a
      lower proportion of CD4(+) and CD4(+)CD45RA(+)RO(-) T cells, a higher proportion
      of CD8(+) and CD4(+)CD38(+)HLADR(+) T cells, and higher HIV-specific CD8(+) T
      cell responses compared to persistently undetectable patients. After cART
      interruption, patients with EIV presented a significantly higher viral rebound
      (p=0.007), associated with greater increases in HIV-specific lymphoproliferative
      responses and T cell populations with activation markers. When patients with EIV
      between 20 and 200 copies/ml were included, most of the differences disappeared.
      Patients who present EIV above 200 copies/ml showed a lower CD4(+) T cell count
      and higher activation markers under cART. After treatment interruption, they
      showed greater specific immune responses against HIV, which did not prevent a
      higher virological rebound. EIV between 20 and 200 copies/ml did not have this
      deleterious effect.

PMID- 23121250
TI  - Quantification of flavonoids in black rice by liquid chromatography-negative
      electrospray ionization tandem mass spectrometry.
AB  - Systematic identification and structural characterization of flavonoids and their
      glycosides in bran extracts of seven Thai black rice varieties were performed by
      sequential uses of reversed-phase HPLC with a photodiode array detector and a
      combined electrospray ionization tandem mass spectrometer. Eleven flavonoids were
      detected, and six of these were found for the first time in rice bran. These were
      taxifolin-7-O-glucoside, myricetin-7-O-glucoside, isorhamnetin-3-O
      acetylglucoside, isorhamnetin-7-O-rutinoside, 5,6,3',4',5'-pentahydroxyflavone-7
      O-glucoside, and 5,3',4',5'-tetrahydroxyflavanone-7-O-glucoside. The quantitative
      results revealed that different rice varieties possessed flavonoids in different
      concentrations. The most abundant glycoside derivative of flavonoids widely
      distributed among the rice varieties was monoglucoside, such as quercetin-3-O
      glucoside, isorhamnetin-3-O-glucoside, and isorhamnetin-3-O-glucoside.

PMID- 23121251
TI  - Peripartum outcomes and anaesthetic management of parturients with moderate to
      complex congenital heart disease or pulmonary hypertension*.
AB  - We performed a retrospective cohort analysis of pregnancies among women with
      moderate to complex congenital heart disease or pulmonary hypertension over a 12
      year period, resulting in a cohort of 107 cases in 65 women. Neuraxial analgesia
      or anaesthesia was provided in 84%, 89% and 95% of spontaneous vaginal, operative
      vaginal and caesarean deliveries, respectively. The caesarean delivery rate was
      43% compared to our institution average of 27% over the same period (p = 0.02),
      and 38% had operative vaginal deliveries compared to a 10.5% institution rate (p
      < 0.01). Invasive monitoring was used in 28% of all deliveries. There were one
      maternal and two neonatal deaths. This study provides detailed anaesthetic and
      peripartum management of women with congenital heart disease, a patient
      population in whom evidence-based practice and data are largely lacking. We
      observed a predominance of neuraxial anaesthetic techniques, increased caesarean
      and operative delivery rates, and favourable maternal and neonatal outcomes.
      Multicentre studies and registries to compare anaesthetic and obstetric
      management strategies further and delineate risk factors for adverse outcomes are
      required.

PMID- 23121252
TI  - Predictors of newly diagnosed atrial fibrillation in cryptogenic stroke: a cohort
      study.
AB  - BACKGROUND AND PURPOSE: A significant proportion of cryptogenic ischaemic strokes
      are due to paroxysmal atrial fibrillation (AF). As paroxysmal AF appears to
      inexorably progress to persistent or permanent AF, this study with long-term
      follow-up was designed to establish the profile of patients who developed AF
      after hospital discharge. METHODS: All patients with cryptogenic ischaemic stroke
      over a 1-year period were included (n = 164). Patients were prospectively
      followed up at the outpatient clinic. Information on long-term outcome included
      the presence of newly diagnosed AF (NDAF). A specific NDAF assessment was
      performed at least 2 years after the index stroke using a structured telephone
      interview. Baseline clinical, laboratory, and echocardiographic data of these
      patients were retrospectively recorded. Independent predictive factors were then
      used to produce a predictive grading score for NDAF, derived by logistic
      regression analysis. RESULTS: With a median follow-up of 854 days, 22 cases of
      NDAF (13%) were observed. On multivariate analysis, factors associated with NDAF
      were age >=72 years (two points), history of coronary artery disease (one point)
      or stroke (one point), and left atrial area >=16 cm(2) (two points) (total score
      ranging from 0 to 6). Patients with a score <=1 point did not have NDAF during
      follow-up. CONCLUSIONS: In cryptogenic ischaemic stroke, the NDAF score can be
      used to target patients at high risk of developing AF after hospital discharge,
      as a score of 0-1 was highly predictive of the absence of NDAF during follow-up.
      These results need to be confirmed in prospective studies.

PMID- 23121254
TI  - Vagus nerve stimulation in children with intractable epilepsy: a randomized
      controlled trial.

PMID- 23121253
TI  - Population genetic correlates of declining transmission in a human pathogen.
AB  - Pathogen control programs provide a valuable, but rarely exploited, opportunity
      to directly examine the relationship between population decline and population
      genetics. We investigated the impact of an ~12-fold decline in transmission on
      the population genetics of Plasmodium falciparum infections (n = 1731) sampled
      from four clinics on the Thai-Burma border over 10 years and genotyped using 96
      genome-wide SNPs. The most striking associated genetic change was a reduction in
      the frequency of infections containing multiple parasite genotypes from 63% in
      2001 to 14% in 2010 (P = 3 * 10(-15)). Two measures of the clonal composition of
      populations (genotypic richness and the beta-parameter of the Pareto
      distribution) declined over time as more people were infected by parasites with
      identical multilocus genotypes, consistent with increased selfing and a reduction
      in the rate at which multilocus genotypes are broken apart by recombination. We
      predicted that the reduction in transmission, multiple clone carriage and
      outbreeding would be mirrored by an increased influence of genetic drift.
      However, geographical differentiation and expected heterozygosity remained stable
      across the sampling period. Furthermore, N(e) estimates derived from allele
      frequencies fluctuation between years remained high (582 to infinity) and showed
      no downward trend. These results demonstrate how genetic data can compliment
      epidemiological assessments of infectious disease control programs. The temporal
      changes in a single declining population parallel to those seen in comparisons of
      parasite genetics in regions of differing endemicity, strongly supporting the
      notion that reduced opportunity for outbreeding is the key driver of these
      patterns.

PMID- 23121255
TI  - A private matter: how patients decide what to do with cryopreserved embryos after
      infertility treatment.
AB  - This study describes patients' satisfaction with the information they received
      regarding the disposition of supernumerary embryos in the context of their
      decision making, as well as partners' roles and the involvement of others. An
      anonymous mail questionnaire was sent to 412 female patients from the Department
      of Reproductive Medicine (Ghent University Hospital, Ghent, Belgium). The
      questionnaire had a response rate of 79%. The majority of patients who did not
      want to continue the storage of their embryos (87.9%) thought the information
      provided was sufficient to make a decision. Patients who were not satisfied more
      often failed to reach a decision compared to other patients (4/25 vs. 6/173, p =
      0.0248). The majority of couples (81.7%) reached a decision jointly between
      partners. Nonetheless, in 15.6% of couples, one of the partners had made the
      decision alone, mostly after consulting their partners. Only a minority of the
      couples (13.2%) consulted others (mostly family members or close friends),
      suggesting that patients view these decisions as a private matter. Only 1.1% of
      all patients had talked to someone at the centre about their decision. To
      conclude, for most patients, the information provided was adequate in light of
      their disposition decision making. Overall, patients' decision making appears to
      be a private matter which happens out of sight from medical staff, making it hard
      to assist patients who face difficulties.

PMID- 23121256
TI  - Salicylic acid peels versus Jessner's solution for acne vulgaris: a comparative
      study.
AB  - BACKGROUND: Salicylic acid was recently formulated in a hydroethanolic vehicle at
      a concentration of 20% to 30%. Salicylic acid has strong comedolytic effects
      because of its lipophilic nature. OBJECTIVE: To compare the therapeutic efficacy
      and tolerability of salicylic acid peels with those of Jessner's solution peels
      in patients with acne vulgaris. METHODS: Thirteen patients (13 men; mean age
      22.6, range 20-28) with facial acne were enrolled. Jessner's solution was applied
      to one side of each patient's face and 30% salicylic acid to the other in three
      sessions at 2-week intervals. A blinded investigator counted noninflammatory and
      inflammatory lesions before treatment and 2 weeks after each treatment. RESULTS:
      Inflammatory and noninflammatory acne lesion counts decreased in proportion to
      the duration of treatment. Inflammatory acne lesion counts did not differ
      significantly between salicylic acid and Jessner's solution peels, although in
      terms of noninflammatory acne lesion counts, sites treated with salicylic acid
      showed significant improvement (p = .04), whereas those treated with Jessner's
      solution did not. CONCLUSION: We found that 30% salicylic acid peels were
      effective for inflammatory acne and more effective than Jessner's solution peels
      for treating noninflammatory acne.

PMID- 23121257
TI  - Resistance to low-dose aspirin therapy among patients with acute coronary
      syndrome in relation to associated risk factors.
AB  - BACKGROUND: A substantial proportion of patients have recurrence of vascular
      events despite daily intake of low-dose aspirin therapy. Therefore, different
      patients may require different aspirin dosages to achieve complete inhibition of
      platelet function. OBJECTIVE: The aim of this work was to measure the response to
      low-dose aspirin therapy (150 mg/day) among patients with unstable angina or non
      ST-segment elevation myocardial infarction and to find out whether titrating
      aspirin dosage to 300 mg/day, would provide a better therapeutic response in the
      resistant cases. Moreover, we also aimed to study any association between aspirin
      non-responsiveness and atherothrombotic risk factors. METHODS: The antiplatelet
      effect of 150 mg/day aspirin was studied prospectively in 50 consecutive patients
      with unstable angina or non-ST-segment elevation myocardial infarction. Platelet
      aggregation was measured using optical platelet aggregometry and serum
      thromboxane B(2) level. Aspirin resistance was defined as collagen (1 MUg/mL) and
      adenosine diphosphate (ADP) (5 MUmol/L)-induced platelet aggregation of >= 40%
      when compared with control values. Twenty healthy age- and sex-matched
      individuals were taken as a control group. All patients were subjected to
      complete medical history (risk factors, medications), thorough clinical
      examination, ECG, coronary angiography and laboratory investigations including:
      complete haemogram, coagulation, kidney, liver and lipid profiles, fasting blood
      glucose and glycated haemoglobin (HbA(1C) ). RESULTS: Eleven of 50 patients (22%)
      were found to be aspirin resistant. A highly significant difference was found
      between the mean values of ADP, collagen-induced platelet aggregation percentage
      and thromboxane B(2) level after aspirin 150 mg/day when compared with the
      corresponding mean values after aspirin 300 mg/day among the resistant patients
      (66 +/- 7.01%, 62 +/- 4.34% and 620 +/- 64.58 pg/mL, respectively, vs. 26.87 +/-
      2.85%, 16.5 +/- 3.8% and 77 +/- 11.3 pg/mL) indicating enhanced response to
      aspirin after escalating the dose. The presence of atherothrombotic risk factors
      (hypertension, smoking, family history of ischaemic heart disease and previous
      MI) were not statistically different between aspirin-resistant and aspirin
      sensitive patients. However, there was a highly significant difference between
      the aspirin sensitive and the resistant patients regarding the other risk factors
      (diabetes mellitus and dyslipidaemia) (P < 0.01). CONCLUSION: There is inter
      individual variability in response to the antiplatelet effect of standard doses
      of aspirin (150, 300 mg/day). The response to aspirin 300 mg/day is enhanced in
      resistant patients when compared to 150 mg/day. There was a significant
      association between aspirin resistance and atherothrombotic risk factors
      (diabetes, hyperlipidaemia and obesity).

PMID- 23121258
TI  - Cognitive behavioural therapy for depression and anxiety in adults with acquired
      brain injury: what works for whom?
AB  - This paper reviews treatment outcome studies on cognitive behavioural therapy
      (CBT) for depression and anxiety following acquired brain injury (ABI), including
      traumatic brain injury (TBI), cerebral vascular accident (CVA), anoxia and
      neurosurgery. Studies are included for review when the published paper included
      an anxiety disorder or depression as the treatment focus, or as part of outcome
      measurement. Relaxed criteria were used to select studies including relevant
      single-cases, case series and single group studies along with studies that
      employed control groups. Twenty-four studies were identified. Twelve papers were
      of a single-case design (with or without replication). Two papers used
      uncontrolled single groups and ten studies used a control group. There were a
      total of 507 people in the various treatment and control groups, which ranged in
      size from 6 to 67 persons. All participants in the study had an ABI. Our review
      indicates CBT often shows a within-group pre- to post-treatment statistical
      difference for depression and anxiety problems, or a statistical difference
      between CBT-treated and non-treated groups. For studies that targeted the
      treatment of depression with CBT, effect-sizes ranged from 0 to 2.39 with an
      average effect-size of 1.15 for depression (large effect). For studies that
      targeted the treatment of anxiety with CBT, effect-sizes ranged from 0 to 3.47
      with an average effect-size of 1.04 for anxiety (large effect). However, it was
      not possible to submit all twenty-four studies identified to effect-size
      analysis. Additionally, it is clear that CBT is not a panacea, as studies
      frequently indicate only partial reduction in anxiety and depression symptoms.
      This review suggests that if CBT is aimed at, for example, anger management or
      coping, it can be effective for anger or coping, but will not generalise to have
      an effect on anxiety or depression. CBT interventions that target anxiety and
      depression specifically appear to generate better therapeutic effects on anxiety
      and depression. Gaps in the literature are highlighted with suggestions for
      future research.

PMID- 23121259
TI  - Retraction: Selective cerebro-myocardial perfusion under mild hypothermia during
      primary repair for aortic coarctation with ventricular septal defect.
AB  - The following article from Artificial Organs, "Selective Cerebro-Myocardial
      Perfusion Under Mild Hypothermia During Primary Repair for Aortic Coarctation
      With Ventricular Septal Defect" by Huiwen Chen, Haifa Hong, Zhongqun Zhu and
      Jinfen Liu, published online on 2 November 2012 in Wiley Online Library
      (wileyonlinelibrary.com), has been retracted by agreement between the authors,
      the journal Editor-in-Chief, Paul S. Malchesky, the International Center for
      Artificial Organs and Transplantation and Wiley Periodicals, Inc. The retraction
      has been agreed due to simultaneous publication of a substantially similar
      article, "Continuous Cerebral and Myocardial Perfusion During One-Stage Repair
      for Aortic Coarctation With Ventricular Septal Defect", by Huiwen Chen, Haifa
      Hong, Zhongqun Zhu and Jinfen Liu, in Pediatric Cardiology 7 November 2012 [Epub
      ahead of print].

PMID- 23121260
TI  - Hepatitis B virus reactivation during therapy with ustekinumab for psoriasis in a
      hepatitis B surface-antigen-negative anti-HBs-positive patient.

PMID- 23121261
TI  - Use of agent-based modelling to predict benefits of cleaner fish in controlling
      sea lice, Lepeophtheirus salmonis, infestations on farmed Atlantic salmon, Salmo
      salar L.
AB  - Sea lice, Lepeophtheirus salmonis, are ectoparasites of farmed and wild
      salmonids. Infestations can result in significant morbidity and mortality of
      hosts in addition to being costly to control. Integrated pest management
      programmes have been developed to manage infestations, and in some salmon farming
      areas, these programmes include the use of wrasse. Wrasse prey upon the parasitic
      life stages of L. salmonis and can be stocked on farms at varying densities.
      Despite considerable variation in the usage of wrasse, there are few quantitative
      estimates of how well they can control sea lice and how best to optimize their
      use. To explore at what densities wrasse should be stocked in order to meet
      specific control targets, we built an individual-based model that simulates sea
      lice infestation patterns on a representative salmonid host. Sea lice can be
      controlled through the use of chemical treatments as well as by wrasse predators.
      We found that the wrasse can effectively control sea lice, and the densities of
      wrasse needed for effective control depend upon the source of the infestation and
      the targeted level of control. Effective usage of wrasse can result in decreased
      use of chemical treatments and improved control of sea lice.

PMID- 23121262
TI  - Bruxism defined and graded: an international consensus.
AB  - To date, there is no consensus about the definition and diagnostic grading of
      bruxism. A written consensus discussion was held among an international group of
      bruxism experts as to formulate a definition of bruxism and to suggest a grading
      system for its operationalisation. The expert group defined bruxism as a
      repetitive jaw-muscle activity characterised by clenching or grinding of the
      teeth and/or by bracing or thrusting of the mandible. Bruxism has two distinct
      circadian manifestations: it can occur during sleep (indicated as sleep bruxism)
      or during wakefulness (indicated as awake bruxism). For the operationalisation of
      this definition, the expert group proposes a diagnostic grading system of
      'possible', 'probable' and 'definite' sleep or awake bruxism. The proposed
      definition and grading system are suggested for clinical and research purposes in
      all relevant dental and medical domains.

PMID- 23121263
TI  - DNA polymerase beta gap-filling translesion DNA synthesis.
AB  - Although the primary function of DNA polymerase (pol) beta is associated with gap
      filling DNA synthesis as part of the DNA base excision repair pathway,
      translesion synthesis activity has also been described. To further understand the
      potential role of pol beta-catalyzed translesion DNA synthesis (TLS) and the
      structure-function relationships of specific residues in pol beta, wild-type and
      selected mutants of pol beta were used in TLS assays with DNA substrates
      containing bulky polycyclic aromatic hydrocarbon-adducted oligonucleotides.
      Stereospecific (+) and (-)-anti-trans-(C(10)S and C(10)R) benzo[a]pyrene-7,8
      dihydrodiol-9-10-epoxide (BPDE) adducts were covalently attached to both the N(6)
      adenine and N(2)-guanine in the major and minor grooves, respectively. For all
      substrates tested, the presence of the BPDE adducts greatly decreased the
      efficiency of nucleotide incorporation opposite the lesion, and the
      stereochemistry of the adducts also further modulated the efficiency of the
      insertion step, such that lesions which were oriented in the 3' direction
      relative to the approaching polymerase were considerably more blocking than those
      oriented in the 5' direction. In the absence of a downstream DNA strand, the
      extension step beyond the adduct was extremely inefficient, relative to a
      dinucleotide gap-filling reaction, such that in the presence of the downstream
      DNA, dinucleotide incorporation was strongly favored. In general, analyses of the
      TLS activities of four pol beta mutants revealed similar overall properties, but
      wild-type pol beta exhibited more than 50-fold greater extension and bypass of
      the C(10)S-dA adducts as compared to a low fidelity mutant R283K expected to
      interact with the templating base. Replication bypass investigations were further
      extended to include analyses of HIV-1 reverse transcriptase, and these studies
      revealed patterns of inhibition very similar to that observed for pol beta.

PMID- 23121264
TI  - Risk factors for surgical site infection in breast surgery.
AB  - AIMS AND OBJECTIVES: To study risks of surgical site infection in breast surgery.
      The objectives were to measure the association of postoperative infection with
      patient- and procedure-related factors. BACKGROUND: The infection rate in breast
      surgery is expected to be low but it varies a lot. The variation is recommended
      to be assessed by measuring procedure-related factors. DESIGN: A retrospective
      chart review of 982 breast surgery patients was completed. METHODS: The data on
      patient demographics, procedure types, patient and surgery-related factors were
      collected. A multivariate logistic regression model for all breast operations
      (n=982), lumpectomies (n=700) and mastectomies (n=282) was performed. RESULTS:
      The infection rate was 6.7%. In a multivariate logistic regression model for all
      operations, a contaminated or dirty wound, high American Society of
      Anesthesiologists score, high body mass index, use of surgical drains and re
      operation predicted increased infection risk. In lumpectomies high body mass
      index and use of surgical drains predicted increased risk. In mastectomies, the
      significant predictor was re-operation. CONCLUSIONS: The surgical site infection
      rate was high. In addition to the two classical risks (high wound class and
      anaesthesia risk), high body mass index, re-operation and use of surgical drain
      increased the infection risk among all patients. RELEVANCE TO CLINICAL PRACTICE:
      In breast surgery careful assessment, documentation and adherence to aseptic
      practices are important with all patients. Patients with heavy weight need
      special attention. The need for antimicrobial prophylaxis in re-operations and
      the need of surgical drains in lumpectomies are important to consider carefully.

PMID- 23121265
TI  - Open innovation: the new face of pharmaceutical research and development.

PMID- 23121266
TI  - Pharmacovigilance in Europe: direction of travel in a changing environment.

PMID- 23121267
TI  - Viral vectors: promising new therapeutics in the battle against glioblastoma.

PMID- 23121268
TI  - Medicines for pediatric oncology: can we overcome the failure to deliver?

PMID- 23121269
TI  - Researchers announce launch of latest HIV microbicide trial.

PMID- 23121270
TI  - Pegloticase and the patient with treatment-failure gout.
AB  - Gout is an inflammatory arthritis characterized by sudden, painful inflammation.
      Gout can affect any joint in an asymmetric distribution. Gouty attacks may be
      isolated or can be followed by years of recurrent flares. Over time, elevated
      serum urate levels and tophaceous deposits can lead to deformity and disability
      from underlying bony erosion. The concept of 'treatment-failure gout' describes a
      unique population that has been either unable to tolerate allopurinol or who have
      not experienced normalization of serum urate levels on allopurinol. It is
      estimated that approximately 1-1.5% of the estimated 3-8 million people with gout
      in the USA have treatment-failure gout. Pegloticase is an US FDA-approved
      intravenous medication that is a mammalian recombinant uricase conjugated to
      monomethoxy polyethylene glycol. Two recent Phase III trials have found
      pegloticase to be effective in the management of treatment-failure gout. These
      studies also highlight safety concerns regarding the drug's immunogenicity.

PMID- 23121271
TI  - Early response of ceftaroline fosamic in the treatment of soft-tissue infections.
AB  - The US FDA recently approved ceftaroline tosamil (ceftaroline) for the treatment
      of acute bacterial skin and soft structure infections (ABSSSIs) and community
      acquired pneumonia. In 2010, the FDA specified a new primary end point for ABSSSI
      of 3 days instead of the traditional test of cure. Friedland et al. used the new
      FDA end point in evaluating the CANVAS 1 and 2 trials. In the exploratory
      modified, intention-to-treat analysis, ceftaroline showed a superior clinical
      response at day 3 (74 vs 66.2%; difference 7.7%; 95% CI: 1.3-14%). The superior
      response of ceftaroline has biologic plausibility based on the in vitro activity
      of the antibiotic, suggesting that a true early clinical benefit may exist.
      However, owing to the potential for selection bias and lack of logistic
      regression analysis, caution should be used when extrapolating these results to
      clinical practice. Future trials utilizing this new end point in prospective
      ABSSSI trials will show over time the true value of such an end point.

PMID- 23121272
TI  - Efficacy, end points and eventualities: sumatriptan/naproxen versus
      butalbital/paracetamol/caffeine in the treatment of migraine.
AB  - Migraine is a widespread, relapsing, remittent syndrome. No animal model predicts
      whether test medications will be clinically useful. Using a modern, well
      controlled, sophisticated study design, Derosier et al. demonstrates not only
      that a butalbital formulation has modest efficacy as an acute treatment for
      migraine but also that a sumatriptan-naproxen combination is superior. These
      conclusions are reached using a variety of internally consistent secondary
      efficacy end points. The primary end point chosen (highly conservative and
      fashionable in some academic circles) was a technical failure (and not a negative
      experimental finding). Migraine is intrinsically pleiomorphic: diverse treatment
      options help match patient with therapy. This study does not justify blanket bans
      on (admittedly hazardous) barbiturate therapies, and regulators should not impose
      end point conservatism to an extent that will stifle further progress.

PMID- 23121273
TI  - Clinical trials involving the oncolytic virus, reovirus: ready for prime time?
AB  - The use of oncolytic viruses as a potential cancer therapeutic has been studied
      extensively over the past 15 years and is now in Phase III human clinical
      testing. One of the most promising of the viruses is the nonattenuated reovirus
      type-3 Dearing (RT3D; Reolysin((r)), Oncolytics Biotech Inc., AB, Canada). The
      virus is a laboratory strain of a ubiquitous common environmental virus commonly
      infecting the respiratory and GI tracts of humans without major sequelae. The
      Phase I/II clinical trial conducted by Karapanagiotou et al. involved dose
      escalation of Reolysin to 3 * 10(10) tissue culture infectious dose 50 (TCID(50))
      daily for 5 days in combination with paclitaxel (175 mg/m(2)) and carboplatin
      (area under the curve 5) given on day 1 every 3 weeks. Maximum tolerated dose was
      not reached in the dose-escalation phase and was only limited by manufacturing
      concentration limitation. Efficacy was suggested in this heavily pretreated head
      and neck cancer predominate patient population with a 26.9% response rate (seven
      out of 26 evaluable patients) of the 34 patients intended to treat. Although this
      was not a randomized trial, the fact that many of the patients (83%) had already
      received a platinum agent and subsequently progressed and then responded is of
      interest.

PMID- 23121274
TI  - A pharmacokinetic approach to assess artemisinin-naphthoquine combination therapy
      for uncomplicated pediatric malaria.
AB  - Artemisinin-based combination therapies (ACTs) have been adopted as the first
      line of treatment against malaria in nearly all malaria-endemic countries, mainly
      as a result of Plasmodium falciparum infection, as this species of malaria
      parasite has developed resistance to most of the available non-artemisinin
      antimalarial drugs. Artemisinin-naphthoquine (ART-NQ, also named as ARCOTM;
      Kunming Pharmaceuticals, Kunming, China) is one of the several currently
      available ACTs that show a promising approach to dealing with drug-resistant
      malaria rather than monotherapies. Unlike other ACTs, ART-NQ requires either a
      single-dose treatment or a two-dose treatment within 24 h against uncomplicated
      P. falciparum malaria; however, this was mainly validated in adults rather than
      children. Batty et al. performed the first pharmacokinetic study of ART-NQ
      combination therapy for uncomplicated pediatric malaria, and the authors' results
      are described and discussed below.

PMID- 23121275
TI  - Evidence-based guidelines for pediatric clinical trials: focus on StaR Child
      Health.
AB  - Clinical trials in children are challenging and filled with important ethical
      considerations that differ from adults. Given difficulties associated with
      pediatric clinical trials, off-label prescribing is a common practice in
      pediatrics, which can lead to adverse safety events and efficacy failures. To
      overcome these consequences, in the past 15 years, legislation in the USA and
      Europe has provided incentives to industry and increased government funding to
      conduct pediatric trials. Pediatric trial networks have also been formed to
      decrease the knowledge gap. However, challenges to performing pediatric trials
      and lack of standardization and guidelines regarding studies in children still
      exist. Standards for Research (StaR) in Child Health, begun in 2009, aims to
      improve the design, conduct and reporting of pediatric trials. This organization
      uses a consensus guideline approach involving academic, government and industry
      stakeholders to identify and disseminate best practices for pediatric trials. Six
      out of 11 planned standards are currently published.

PMID- 23121276
TI  - Novel therapeutics for gastro-esophageal reflux symptoms.
AB  - Approximately 20-30% of patients with gastro-esophageal reflux symptoms report
      inadequate symptom relief while on proton-pump inhibitor therapy. The mechanisms
      involved are failure of the antireflux barrier (transient lower esophageal
      sphincter relaxations), high proximal extent of the refluxate, esophageal
      hypersensitivity and impaired mucosal integrity. Persisting acid or nonacid
      reflux can be demonstrated in 40-50% of cases, suggesting that there is room for
      antireflux therapy in these patients. New antireflux compounds have been shown to
      decrease the occurrence of transient lower esophageal sphincter relaxations. The
      most promising classes of compounds are GABA type B agonists and metabotropic
      glutamate receptor 5 antagonists, which can reduce both reflux episodes and
      symptoms, but the development of these compounds has been abandoned for either
      safety issues or lack of efficacy. Esophageal hypersensitivity and impaired
      mucosal integrity may prove to be relevant therapeutic targets in the future.

PMID- 23121277
TI  - New biologic-response modifiers in ocular inflammatory disease: beyond anti-TNF
      treatment.
AB  - Current treatment guidelines for chronic ocular inflammatory disease recommend
      the use of steroid-sparing agents. The development of conventional
      immunomodulatory agents has largely changed the visual outcome in these patients.
      However, disease refractory to these treatment modalities has led to the use of
      new biologic-response modifiers, agents that target specific components of the
      pathogenetic process. The purpose of this review is to summarize the mechanism of
      action, experimental evidence, side effects and current experience with the use
      of rituximab, daclizumab, abatacept, anakinra and IFN-alpha in ocular
      inflammatory disease.

PMID- 23121278
TI  - Safety of pharmacoenhancers for HIV therapy.
AB  - HIV protease inhibitors have been part of highly active therapy regimens
      throughout the past 16 years of antiretroviral therapy. The majority of currently
      available protease inhibitors are coadministered with low-dose ritonavir (RTV) as
      a pharmacoenhancer, significantly increasing their plasma concentrations. This
      therapeutic principle called 'boosting' helped to overcome the obstacles of this
      class of drugs concerning unfavorable pharmacokinetics, resulting in either a
      high frequency of dosing or subtherapeutic plasma concentrations. The
      coadministration of RTV together with HIV protease inhibitors created a potent,
      clinically effective antiretroviral therapy, which is more convenient for the
      patient, and has revealed a high genetic barrier to viral resistance. RTV is the
      only pharmacoenhancing agent available to date; however, cobicistat, a selective
      CYP3A4 inhibitor, is about to enter the market. This article reviews current
      literature, compares the safety of both pharmacoenhancers and appraises their use
      in current and future HIV therapy.

PMID- 23121279
TI  - Induction of cytochrome P450 enzymes: a view on human in vivo findings.
AB  - The induction of drug-metabolizing enzymes is a special case of pharmacokinetic
      interactions with consequences for the concurrent drug therapy. The most
      important enzymes affecting the pharmacokinetics of pharmaceuticals are
      cytochrome P450 (CYP) enzymes and their induction is often of utmost importance
      for the effects of the metabolized drugs. This review presents the current
      knowledge on the inducers of the specific CYP enzymes in humans. The focus is
      solely on human in vivo findings; in vitro results are referenced only when
      needed to interpret the induction mechanisms. As the mechanisms of CYP induction
      are important in understanding the effects of inducers, a concise overview of the
      various receptors affecting the induction of human CYP enzymes is presented.

PMID- 23121280
TI  - The adverse pharmacology of calcineurin inhibitors and their impact on hepatitis
      C recurrence after liver transplantation: implications for clinical practice.
AB  - Calcineurin inhibitors are widely used as maintenance immunosuppressants in solid
      organ transplantation to minimize the risk of allograft rejection. Although the
      use of these agents has transformed the outcomes for patient and graft survival,
      this has come at a cost, notably the well-known adverse events of nephrotoxicity
      and metabolic abnormalities, to name a few. Over the last decade, tremendous
      interest has also focused on the impact of these medications on the replication
      of hepatitis C virus (HCV), with cyclosporine in particular having a negative
      effect on viral replication in vitro. Although small retrospective studies
      suggested that there may be a beneficial effect with cyclosporine on the
      progression of recurrent HCV and response to interferon, these findings have not
      been validated in several well-designed randomized controlled trial studies. The
      authors will review the pharmacology and pharmacokinetics of these well-known
      drugs and discuss the impact of these medications on the natural history of HCV
      recurrence after liver transplantation.

PMID- 23121282
TI  - Intelligent materials with adaptive adhesion properties based on comb-like
      polymer brushes.
AB  - We investigated the adaptive adhesion properties of comb-like random copolymer
      brushes made of poly(ethylene glycol) (PEG)-poly(dimethylsiloxane) (PDMS) grafted
      on flat and rough substrates. The properties of the brush layers were
      investigated using ARXPS, contact angle, electrokinetics, null ellipsometry, and
      adhesion measurements. It was found that hydrophobic PDMS segments segregate at
      the brush topmost layer in the dry state. However, hydrophilic PEG chains
      segregate at the brush topmost layer in the wet state. The adhesion properties of
      fabricated materials were tested using the AFM colloid probe technique and probe
      tack tester. It was found that the adhesive properties depend strongly on the
      mechanical properties (stiff/soft) and chemical functionality
      (hydrophobicity/hydrophilicity) of the applied adhesion tester as well as on the
      chemical composition, surface roughness, and thickness of the brush. In
      particular, hydrophobic PDMS and hydrophilic PEG adhere more strongly to
      hydrophobically modified and hydrophilic native colloid probes, respectively.
      Thick brushes are more adhesive than thin ones, and brushes grafted to flat
      substrates are stickier than those grafted to rough substrates when measured with
      a hard AFM probe. Unlike the results of adhesion measurements performed using
      hard AFM probes, the PDMS surface probed by soft pressure-sensitive adhesives
      (PSA) is almost nonadhesive. However, PEG is strongly adhesive, and the adhesion
      increases with the PEG fraction in the brush when probed by both hydrophilic and
      hydrophobic soft adhesives. The surfaces roughness also has a considerable effect
      on adhesion. Contrary to the adhesion measurements performed by hard AFM colloid
      probes, the adhesion of rough surfaces measured with a soft PAA or SIS tack
      tester is greater than that on the corresponding flat one.

PMID- 23121285
TI  - MicroRNA-137 promoter methylation in oral lichen planus and oral squamous cell
      carcinoma.
AB  - Oral lichen planus (OLP) is a common oral mucosal disease, which is generally
      considered a potentially malignant lesion. To identify efficiently prognostic
      biomarker, we investigated the microRNA-137 (miR-137) promoter methylation in OLP
      and compared with the samples from healthy volunteers and patients with oral
      squamous cell carcinoma (OSCC). A total of 20 OLP and 12 patients with OSCC as
      well as 10 healthy subjects were subjected to miR-137 promoter methylation
      analysis using methylation-specific PCR (MSP). To address the malignancy
      prediction potential from miR-137 promoter methylation status, methylation of the
      p16 gene, a well-known tumor suppressor, was investigated in the same samples.
      The p16 methylation and miR-137 promoter methylation were found to be 25% and 35%
      in patients with OLP, 50% and 58.3% in patients with OSCC, and 0% and 0% in
      healthy subjects, respectively. The differences between miR-137 and p16
      methylation levels were statistically significant between healthy controls and
      patients. Methylation levels of the two promoters were also influenced by age,
      gender, and lesion duration. Interestingly, aberrant promoter methylation of the
      p16 and miR-137 genes was only found in the epithelium but not in the connective
      tissue from patients with OLP. This raises the possibility to use miR-137
      methylation as a biomarker for malignant prediction in patients with OLP.

PMID- 23121286
TI  - Elevated potassium provides an ionic mechanism for deep brain stimulation in the
      hemiparkinsonian rat.
AB  - The mechanism of high-frequency stimulation used in deep brain stimulation (DBS)
      for Parkinson's disease (PD) has not been completely elucidated. Previously, high
      frequency stimulation of the rat entopeduncular nucleus, a basal ganglia output
      nucleus, elicited an increase in [K(+)](e) to 18 mm, in vitro. In this study, we
      assessed whether elevated K(+) can elicit DBS-like therapeutic effects in
      hemiparkinsonian rats by employing the limb-use asymmetry test and the self
      adjusting stepping test. We then identified how these effects were meditated with
      in-vivo and in-vitro electrophysiology. Forelimb akinesia improved in
      hemiparkinsonian rats undergoing both tests after 20 mm KCl injection into the
      substantia nigra pars reticulata (SNr) or the subthalamic nucleus. In the SNr,
      neuronal spiking activity decreased from 38.2 +/- 1.2 to 14.6 +/- 1.6 Hz and
      attenuated SNr beta-frequency (12-30 Hz) oscillations after K(+) treatment. These
      oscillations are commonly associated with akinesia/bradykinesia in patients with
      PD and animal models of PD. Pressure ejection of 20 mm KCl onto SNr neurons in
      vitro caused a depolarisation block and sustained quiescence of SNr activity. In
      conclusion, our data showed that elevated K(+) injection into the
      hemiparkinsonian rat SNr improved forelimb akinesia, which coincided with a
      decrease in SNr neuronal spiking activity and desynchronised activity in SNr beta
      frequency, and subsequently an overall increase in ventral medial thalamic
      neuronal activity. Moreover, these findings also suggest that elevated K(+) may
      provide an ionic mechanism that can contribute to the therapeutic effects of DBS
      for the motor treatment of advanced PD.

PMID- 23121287
TI  - Construction of gene regulatory networks mediated by vegetative and reproductive
      stage-specific small RNAs in rice (Oryza sativa).
AB  - Although huge amounts of high-throughput sequencing (HTS) data are available,
      limited systematic analyses have been performed by integrating these valuable
      resources. Based on small RNA (sRNA), RNA and degradome HTS data, the sRNAs
      specifically expressed at vegetative and reproductive stages were identified
      separately in rice. Two distinct groups of sRNA HTS data, which were prepared
      during the vegetative and the reproductive stages, were utilized to extract stage
      specific sRNAs. Degradome sequencing data were employed for sRNA target
      validation. RNA sequencing data were used to construct expression-based, sRNA
      mediated networks. As a result, 26 microRNAs and 413 sRNAs were specifically
      expressed at the vegetative stage, and 79 microRNAs and 539 sRNAs were
      specifically expressed at the reproductive stage. In addition to the microRNAs,
      numerous stage-specific sRNAs enriched in ARGONAUTE1 showed great potential to
      perform cleavage-based repression on the targets. Several stage-specific sRNAs
      were indicated to result from the wobble effect of Dicer-like 1-mediated
      processing of microRNA precursors. The expression patterns of the sRNA targets,
      and the stage-specific cleavage signals strongly indicated the reliability of the
      constructed networks. A set of rice stage-specific sRNAs along with the
      regulatory cascades, which have great potential in regulating specific
      developmental stages, were provided for further investigation.

PMID- 23121288
TI  - Recent developments in high-performance liquid chromatography stationary phases.

PMID- 23121289
TI  - When less is more: the forbidden fruits of gene repression in the adult beta
      cell.
AB  - Outside of the biological arena the term 'repression' often has a negative
      connotation. However, in the pancreatic beta-cell a small group of genes, which
      are abundantly expressed in most if not all other mammalian tissues, are highly
      selectively repressed, with likely functional consequences. The two 'founder'
      members of this group, lactate dehydrogenase A (Ldha) and monocarboxylate
      transporter-1 (MCT-1/Slc16a1), are inactivated by multiple mechanisms including
      histone modifications and microRNA-mediated silencing. Their inactivation ensures
      that pyruvate and lactate, derived from muscle during exercise, do not stimulate
      insulin release inappropriately. Correspondingly, activating mutations in the MCT
      1 promoter underlie 'exercise-induced hyperinsulinism' (EIHI) in man, a condition
      mimicked by forced over-expression of MCT-1 in the beta-cell in mice.
      Furthermore, LDHA expression in the beta-cell is upregulated in both human type 2
      diabetes and in rodent models of the disease. Recent work by us and by others has
      identified a further ~60 genes which are selectively inactivated in the beta
      cell, a list which we refine here up to seven by detailed comparison of the two
      studies. These genes include key regulators of cell proliferation and stimulus
      secretion coupling. The present, and our earlier results, thus highlight the
      probable importance of shutting down a subset of 'disallowed' genes for the
      differentiated function of beta-cells, and implicate previously unsuspected
      signalling pathways in the control of beta-cell expansion and insulin secretion.
      Targeting of deregulated 'disallowed' genes in these cells may thus, in the
      future, provide new therapeutic avenues for type 2 diabetes.

PMID- 23121290
TI  - Modulation of methuselah expression targeted to Drosophila insulin-producing
      cells extends life and enhances oxidative stress resistance.
AB  - Ubiquitously reduced signaling via Methuselah (MTH), a G-protein-coupled receptor
      (GPCR) required for neurosecretion, has previously been reported to extend life
      and enhance stress resistance in flies. Whether these effects are due to reduced
      MTH signalling in specific tissues remains unknown. We determined that reduced
      expression of mth targeted to the insulin-producing cells (IPCs) of the fly brain
      was sufficient to extend life and enhance oxidative stress resistance.
      Paradoxically, we discovered that overexpression of mth targeted to the same
      cells has similar phenotypic effects to reduced expression due to MTH's
      interaction with beta-arrestin, which uncouples GPCRs from their G-proteins. We
      confirmed the functional relationship between MTH and beta-arrestin by finding
      that IPC-targeted overexpression of beta-arrestin alone mimics the longevity
      phenotype of reduced MTH signaling. As reduced MTH signaling also inhibits
      insulin secretion from the IPCs, the most parsimonious mechanistic explanation of
      its longevity and stress-resistance enhancement might be through reduced
      insulin/IGF signaling (IIS). However, examination of phenotypic features of long
      lived IPC-mth modulated flies as well as several downstream IIS targets
      implicates enhanced activity of the JNK stress-resistance pathway more directly
      than insulin signaling in the longevity and stress-resistance phenotypes.

PMID- 23121291
TI  - Split-hand plus sign in ALS: differential involvement of the flexor pollicis
      longus and intrinsic hand muscles.
AB  - The flexor pollicis longus (FPL), a key muscle involved in fractionated thumb
      movements, may be relatively spared in amyotrophic lateral sclerosis (ALS)
      compared to the thenar group of muscles, termed the split-hand plus sign.
      Consequently, the diagnostic utility of the split-hand plus sign was
      prospectively assessed in ALS. In total, 103 patients (37 ALS and 66 non-ALS)
      with neuromuscular symptoms underwent assessment of FPL and APB strength using
      the Medical Research Council (MRC) score. A median nerve strength index (MSI) was
      developed to quantify differential involvement by expressing the APB strength
      score as a fraction of the FPL strength score. The APB muscle strength was
      significantly reduced compared to FPL strength in ALS patients (p < 0.0001), but
      was comparable in the non-ALS disorders (p = 0.91). In addition, there was a
      significant reduction of MSI scores in ALS patients (MSIALS 0.8; MSInon-ALS 1.0,
      p < 0.01). Analysis of receiver operating characteristic (ROC) curves disclosed
      that MSI < 0.9 exhibited an area under the curve of 0.86 (p < 0.001) with a
      sensitivity of 85% and specificity of 86% for limb-onset ALS. In conclusion,
      split-hand plus sign distinguished ALS from non-ALS neuromuscular disorders,
      thereby suggesting a diagnostic utility of this novel clinical sign in ALS.

PMID- 23121292
TI  - The Drosophila homologue of tubulin-specific chaperone E-like protein is required
      for synchronous sperm individualization and normal male fertility.
AB  - The tubulin-specific chaperone E-like protein (TBCEL or E-like) of vertebrates
      shows sequence homology to TBCE, a component of the multimolecular complex
      required for tubulin heterodimer formation in all eukaryotic cells. TBCEL
      apparently serves more specific functions, as it is found only in animals. At the
      cellular level, TBCEL plays a role as a regulator of tubulin stability. It is
      strongly expressed in human testes, but its systemic function is not known. The
      gene CG12214 codes for the Drosophila homologue of the vertebrate TBCEL protein.
      Here we show that disruption of the Drosophila Tbcel gene causes defects in
      spermatid individualixation, which leads to dispersed migration of F-actin-rich
      investment cones. Mutations affecting the Tbcel gene cause strong reduction in
      male, but not female, fertility. However, mature sperm function apparently is not
      impaired. We generated polyclonal antisera against TBCEL to study its
      localization and distribution in Drosophila tissues. Immunostainings of wild-type
      and null mutant testes demonstrated that TBCEL is localized in testes, presumably
      associated with axoneme bundles prior to spermatid individualization. Molecular
      analysis of the transposon insertion site in the mutant mulet (mlt), for which
      male sterility and sperm individualization defects have previously been
      described, demonstrates that the mlt P-element insertion resides in the Tbcel
      gene. Our results show that loss of TBCEL in Drosophila is compatible with
      viability and normal female fertility but causes reduced male fertility. We
      conclude that Drosophila TBCEL is strongly expressed in testes and plays an
      important role in sperm individualization during spermatogenesis. The high level
      of Tbcel mRNA in human testes suggests a general role of TBCEL in animal
      spermatogenesis. However, Western blots and courtship analysis suggest that TBCEL
      may have additional functions in the nervous system of Drosophila that could
      contribute to the observed reduced male fertility. These functions now have to be
      investigated.

PMID- 23121293
TI  - A lateral flow immunoassay for the rapid detection of ochratoxin A in wine and
      grape must.
AB  - A one-step lateral flow immunoassay was developed for semiquantitatively
      detecting ochratoxin A (OTA) in wines and grape musts. Matrix-matched calibration
      curves carried out in blank wines showed a detection limit of 1 MUg L(-1) and
      IC(50) of 3.2 MUg L(-1). Relative standard deviations for intra- and interday
      precision were in the 20-40% range. A simple treatment of samples, which only
      included dilution with sodium bicarbonate and polyethylene glycol (4% w/v) for
      red and white wines and the further addition of ethanol (12% v/v) for grape
      musts, was established. The developed assay allowed OTA detection in 5 min and
      proved to be accurate and sensitive enough to allow the correct attribution of
      samples as compliant or noncompliant according to EU legislation. Results
      agreeing with those of a reference chromatographic method were obtained on 38
      wines and 16 musts. Although some lateral flow devices aimed at detecting OTA
      have been previously described, this is the first assay capable of measuring the
      toxin in wine and grape must, which represent a major source of OTA dietary
      intake. Analytical performances of the method are comparable to or better than
      previously reported assays showed. In addition, the assay, including sample
      treatments, is extremely simple and rapid and can be effectively regarded as a
      one-step assay usable virtually anywhere.

PMID- 23121294
TI  - Haemophagocytic lymphohistiocytosis in a patient with severe burns.
AB  - Recently, increasing attention has been drawn to haemophagocytic
      lymphohistiocytosis as a potentially under-diagnosed condition in critically ill
      patients with severe sepsis. It is thought to be caused by a highly stimulated,
      but ineffective, immune system. We report the case of a patient suffering from
      major burns who, despite extensive investigations showing the absence of
      concurrent sepsis or infection, developed haemophagocytic lymphohistiocytosis
      refractory to treatment. We believe that this is the first report suggestive of
      haemophagocytic lymphohistiocytosis triggered by a burns injury.

PMID- 23121295
TI  - Genotype matching in a parasitoid-host genotypic food web: an approach for
      measuring effects of environmental change.
AB  - Food webs typically quantify interactions between species, whereas evolution
      operates through the success of alleles within populations of a single species.
      To bridge this gap, we quantify genotypic interaction networks among individuals
      of a single specialized parasitoid species and its obligate to cyclically
      parthenogenetic aphid host along a climatic gradient. As a case study for the
      kinds of questions genotype food webs could be used to answer, we show that
      genetically similar parasitoids became more likely to attack genetically similar
      hosts in warmer sites (i.e. there was network-wide congruence between the within
      species shared allelic distance of the parasitoid and that of its host).
      Narrowing of host-genotype-niche breadth by parasitoids could reduce resilience
      of the network to changes in host genetic structure or invasion by novel host
      genotypes and inhibit biological control. Thus, our approach can be easily used
      to detect changes to sub-species-level food webs, which may have important
      ecological and evolutionary implications, such as promoting host-race
      specialization or the accelerated loss of functional diversity following
      extinctions of closely related genotypes.

PMID- 23121296
TI  - Recognizable phenotypes associated with intracranial calcification.
AB  - AIM: In this observational study, we adopted a systematic approach to the
      radiological phenotyping of disorders associated with intracranial calcification,
      with the aim of determining if characteristic patterns could be defined as an aid
      to the future diagnosis of known conditions and the identification of new
      disorders. METHOD: A cranial imaging-based scoring system was devised using both
      computed tomography and magnetic resonance imaging data. Patients were grouped
      into diagnostic categories where a definitive molecular diagnosis was known, or
      where the clinical and radiological features suggested a specific diagnosis. For
      patients in whom the diagnosis was unknown, subgroups were defined according to
      shared radiological features. RESULTS: Data on 244 scans from 119 patients were
      analysed. A specific diagnosis was available for 59 patients (31 males, 28
      females; median age 50 mo, range 1 wk to 54 y). These were as follows (number of
      patients in brackets): Aicardi-Goutieres syndrome (33), cerebroretinal
      microangiopathy with calcification and cysts (10), band-like calcification with
      simplified gyration and polymicrogyria (6), COL4A1-related disease (3), Degos
      disease (2), Krabbe disease (2), Alexander disease (1), mitochondrial disease
      (1), and tetrasomy 15 (1). In 60 patients the aetiology was unknown. Within this
      group, subsets demonstrating shared characteristics suggestive of a specific
      calcification phenotype could be identified. INTERPRETATION: This study confirms
      the value of a systematic approach to radiological phenotyping of disorders
      associated with intracranial calcification.

PMID- 23121297
TI  - Deep subcortical infarct burden in relation to apolipoprotein B/AI ratio in
      patients with intracranial atherosclerotic stenosis.
AB  - BACKGROUND AND PURPOSE: Pre-existing brain infarct (PBI), frequently seen on
      magnetic resonance imaging and usually silent, is recognized as a risk factor for
      future stroke. Increased apolipoprotein B (apoB)/apoAI ratio is known to be a
      risk predictor of ischaemic stroke and is associated with intracranial
      atherosclerotic stenosis (ICAS). However, little is known about the association
      of apoB/apoAI ratio with PBI. METHODS: A total of 522 statin-/fibrate-naive
      Korean patients, who experienced acute ischaemic stroke, were categorized into
      three groups: ICAS (n=254), extracranial (n=51), and no cerebral atherosclerotic
      stenosis (n=217). We explored the association between apoB/apoAI ratio and PBI
      lesions according to atherosclerosis type (ICAS, ECAS, and NCAS), PBI location
      (deep subcortical [ds-PBI] versus hemispheric [h-PBI]), and symptomatic PBI (s
      PBI) which was relevant to a prior clinical stroke event. RESULTS: Pre-existing
      brain infarct(+) patients showed a higher apoB/apoAI ratio than PBI(-) patients
      (0.81 +/- 0.28 vs. 0.72 +/- 0.23, P<0.001). In ICAS group, patients with higher
      apoB/apoAI ratio quartiles had more PBIs, ds-PBIs, and s-PBIs (P=0.020, P=0.025,
      and P=0.001, respectively). With multivariable analyses, the highest apoB/apoAI
      ratio quartile was associated with PBI (OR, 2.56; 95% CI, 1.39-4.73), ds-PBI
      (2.48; 1.33-4.62), and advanced (>= 3) ds-PBIs (2.68; 1.27-5.63) in ICAS group,
      but not with h-PBI. s-PBI had a dose-response relationship with apoB/apoAI ratio
      quartiles (6.18; 1.31-29.13 for the second; 5.34; 1.06-26.83 for the third; and
      12.17; 2.50-59.19 for the fourth quartile), when referenced to the first
      quartile. CONCLUSION: ApoB/apoAI ratio is associated with asymptomatic deep
      subcortical ischaemic burden as well as with symptomatic lesion in patients with
      ICAS.

PMID- 23121299
TI  - Clinical and paraclinical guidelines for management of sulfur mustard induced
      bronchiolitis obliterans; from bench to bedside.
AB  - It is well documented that inhalation of sulfur mustard (SM) causes injury to the
      respiratory system. Many Iranian civilians and war veterans are suffering from
      late respiratory complications of SM exposure. Recent studies have shown that
      bronchiolitis obliterans (BO) is the major cause of respiratory complications
      following SM exposure. In this review, we focus on the clinical, pulmonary,
      radiological, immunological and pathological manifestations in SM-induced BO with
      intent to provide a practical, clinical and paraclinical guideline for diagnosis
      and step-wise workup of these patients, which may be used to manage similar lung
      injuries induced by other similar inhaled toxins.

PMID- 23121298
TI  - Development of a rhesus monkey lung geometry model and application to particle
      deposition in comparison to humans.
AB  - The exposure-dose-response characterization of an inhalation hazard established
      in an animal species needs to be translated to an equivalent characterization in
      humans relative to comparable doses or exposure scenarios. Here, the first
      geometry model of the conducting airways for rhesus monkeys is developed based
      upon CT images of the conducting airways of a 6-month-old male, rhesus monkey. An
      algorithm was developed for adding the alveolar region airways using published
      rhesus morphometric data. The resultant lung geometry model can be used in
      mechanistic particle or gaseous dosimetry models. Such dosimetry models require
      estimates of the upper respiratory tract volume of the animal and the functional
      residual capacity, as well as of the tidal volume and breathing frequency of the
      animal. The relationship of these variables to rhesus monkeys of differing body
      weights was established by synthesizing and modeling published data as well as
      modeling pulmonary function measurements on 121 rhesus control animals.
      Deposition patterns of particles up to 10 um in size were examined for
      endotracheal and and up to 5 um for spontaneous breathing in infant and young
      adult monkeys and compared to those for humans. Deposition fraction of respirable
      size particles was found to be higher in the conducting airways of infant and
      young adult rhesus monkeys compared to humans. Due to the filtering effect of the
      conducting airways, pulmonary deposition in rhesus monkeys was lower than that in
      humans. Future research areas are identified that would either allow replacing
      assumptions or improving the newly developed lung model.

PMID- 23121300
TI  - Evaluation of potential for toxicity from subacute inhalation of tire and road
      wear particles in rats.
AB  - Tire and road wear particles (TRWP) are a component of ambient particulate matter
      (PM) produced from the interaction of tires with the roadway. Inhalation of PM
      has been associated with cardiopulmonary morbidities and mortalities thought to
      stem from pulmonary inflammation. To determine whether TRWP may contribute to
      these events, the effects of subacute inhalation of TRWP were evaluated in rats.
      TRWP were collected at a road simulator laboratory, aerosolized, and used to
      expose male and female Sprague-Dawley rats (n = 10/treatment group) at ~10, 40,
      or 100 MUg/m3 TRWP via nose-only inhalation for 6 h/day for 28 days. Particle
      size distribution of the aerosolized TRWP was found to be within the respirable
      range for rats. Toxicity was assessed following OECD guidelines (TG 412). No TRWP
      related effects were observed on survival, clinical observations, body or organ
      weights, gross pathology, food consumption, immune system endpoints, serum
      chemistry, or biochemical markers of inflammation or cytotoxicity. Rare to few
      focal areas of subacute inflammatory cell infiltration associated with TWRP
      exposure were observed in the lungs of one mid and four high exposure animals,
      but not the low-exposure animals. These alterations were minimal, widely
      scattered and considered insufficient in extent or severity to have an impact on
      pulmonary function. Furthermore, it is expected that these focal lesions would
      remain limited and may undergo resolution without long-term or progressive
      pulmonary alterations. Therefore, from this study we identified a no-observable
      adverse-effect-level (NOAEL) of 112 MUg/m3 of TRWP in rats for future use in risk
      assessment of TRWP.

PMID- 23121301
TI  - Involvement of TLR2 and TLR4 and Th1/Th2 shift in inflammatory responses induced
      by fine ambient particulate matter in mice.
AB  - Epidemiologic studies have reported the association between fine particles
      (aerodynamic diameter <= 2.5 MUm; PM2.5) and health effects, but the
      immunological mechanisms are not clear. To investigate the dose and time
      dependent role of toll-like receptor (TLR) and Th1/Th2 shift in local and
      systemic inflammation induced by PM2.5, mice were subjected to intratracheal
      instillation of 2.5, 5, or 10 mg/kg PM2.5 in this study. After 24 h, 72 h, 7
      days, and 14 days, mice were sacrificed to measure TLR2 and TLR4 expressions and
      Th1/Th2 related cytokines in bronchoalveolar lavage fluid (BALF) and peripheral
      blood. Histopathological changes in lung were also examined. Inflammatory
      infiltration and macrophages with engulfed particles were found by lung
      histopathology after PM2.5 exposure. TLR4 positive cells decreased in BALF but
      increased in blood at 24 h after the exposure. The low percentage of TLR4
      positive cells continued to day 14 in BALF, but recovered at day 7 and decreased
      further to lower than the control value at day 14 in blood. TLR2 positive cell
      changed similar to TLR4 in BALF on the dose effects. In BALF at 24 h after the
      exposure, the Th2 related cytokines IL-5 and IL-10 increased dose-dependently;
      and in blood, the Th2 related cytokines IL-4, IL-5, and IL-10 also increased.
      These results suggest that acute exposure of PM2.5 leads to acute inflammatory
      responses locally and systemically in mice. TLR2 and TLR4 are involved in this
      process and PM2.5 can drive a Th2-biased immune response.

PMID- 23121302
TI  - Corrigendum. Are airborne refractory ceramic fibers similar to asbestos in their
      carcinogenicity?

PMID- 23121304
TI  - Saddleback deformities in yellowfin bream, Acanthopagrus australis (Gunther),
      from South East Queensland.

PMID- 23121303
TI  - Individual differences in autistic trait load in the general population predict
      visual working memory performance.
AB  - Prior studies have reported instances of both intact and impaired working memory
      (WM) performance in people with autism spectrum disorder (ASD). In order to
      investigate the relation between autistic traits that extend into the normal
      population and WM, 104 normal college-aged students who varied in their levels of
      autistic traits were tested. The loading of ASD-associated traits in the normal
      population leads to differing predictions about WM performance. ASD traits
      related to a local processing style (or "attention to detail") might enhance WM
      while ASD-associated traits related to difficulty switching attention and
      reorienting focus (or "social interaction") might impair WM performance. To
      assess these predictions, participants filled out the Autism Spectrum Quotient
      (AQ) and performed a working memory task with both visual and verbal variants. AQ
      scores were then broken into "attention to detail" and "social interaction"
      factors, as proposed by Hoekstra and colleagues. The results showed that AQ
      scores did not predict verbal WM performance but they did predict visual WM
      performance. The social interaction and attention to detail factors of the AQ had
      opposing relationships with visual WM performance: A higher level of social
      difficulty was associated with significantly poorer visual WM performance while a
      higher level of attention to detail was associated with enhanced visual WM
      performance. Further investigation of the relation between AQ and WM using the
      original five-factor model proposed by Baron-Cohen and colleagues (2001) revealed
      an association between impoverished imagination and visual WM overall.

PMID- 23121305
TI  - Validation of an enzyme-linked immunosorbent assay for measurement of feline
      serum insulin.
AB  - BACKGROUND: Feline insulin has been measured previously using assays developed
      for measuring human insulin. As feline insulin differs from human insulin, it is
      important to validate the assay before use. OBJECTIVES: The aims of this study
      were to validate an ELISA, the Mercodia Feline Insulin ELISA, intended for
      measuring feline insulin and to determine the stability of feline insulin in
      serum. METHODS: Validation of the ELISA, which uses monoclonal antibodies that
      recognize both human and feline insulin, included evaluation of coefficients of
      variation (CVs), patterns of variation, and consistency after dilution and
      spiking with feline insulin. Stability was evaluated by measuring insulin in
      feline serum samples stored at 20 degrees C, 2-8 degrees C, and -80 degrees C.
      RESULTS: The intra-assay CV in 14-20 adjacent replicates (excluding position
      effects) was 2.0-4.2% and the inter-assay CV was 7.6-14%. The systematic and
      random position effect yielded a CV of 6.2-10%. When 3 feline serum samples were
      set at fixed positions and analyzed on 8 plates, microplate effects and
      interaction were significant for all 3 samples. Recovery upon dilution and
      spiking was 78-105% and 86-126%, respectively. Feline serum insulin concentration
      was stable for 24 hours at 20 degrees C, for 4 days at 2-8 degrees C, and for 15
      months at -80 degrees C. CONCLUSIONS: The Mercodia Feline Insulin ELISA can be
      used for measuring serum feline insulin. Recovery after spiking and dilution was
      acceptable. As in many ELISAs, intra-assay CV for adjacent replicates was low,
      whereas the position and between-assay CVs were considerably higher.

PMID- 23121306
TI  - Child protection guidance needs to address parent behaviour.

PMID- 23121307
TI  - New ways to separate graft-versus-host disease and graft-versus-tumour effects
      after allogeneic haematopoietic stem cell transplantation.
AB  - A major challenge to transplant immunologists and physicians remains the
      separation of harmful graft-versus-host disease (GvHD) and beneficial graft
      versus-tumour (GvT) effects after allogeneic haematopoietic stem cell
      transplantation. Recent advances in our understanding of the allogeneic immune
      response provide potential new opportunities to achieve this goal. Three
      potential new approaches that capitalize on this new knowledge are considered in
      depth; the manipulation of organ-specific cytokines and other pro-inflammatory
      signals, the selective manipulation of donor effector T cell migration, and the
      development of cell-mediated immunosuppressive strategies using donor-derived
      regulatory T cells. These new approaches could provide strategies for local
      control of allogeneic immune responses, a new paradigm to separate GvHD and GvT
      effects. Although these strategies are currently in their infancy and have
      challenges to successful translation to clinical practice, all have exciting
      potential for the future.

PMID- 23121308
TI  - Relationship between Helicobacter pylori infection and serum interleukin-18 in
      patients with carotid atherosclerosis.
AB  - BACKGROUND: Helicobacter pylori (H. pylori) infection stimulates the production
      of proinflammatory cytokines associated with the development of atherosclerosis.
      Levels of circulating interleukin-18 (IL-18) have been positively correlated with
      carotid intima-media thickness (IMT) and coronary plaque area and have identified
      IL-18 levels as important predictors of coronary events and cardiovascular
      mortality. This study aimed to examine the relationship between serum IL-18 and
      H. pylori-IgG antibody as a sign of H. pylori infection in patients with carotid
      atherosclerosis. METHODS: The carotid IMT, traditional atherosclerotic risk
      factors, levels of serum H. pylori-IgG and IL-18 were measured in 573 health
      checkup examinees. RESULTS: Serum IL-18 and H. pylori-IgG levels were
      significantly increased in subjects with increased IMT in comparison with those
      with normal IMT. In subjects with increased IMT, serum H. pylori-IgG was
      positively correlated with serum IL-18 (r = .402, p = .002), and the association
      was independent of traditional atherosclerotic risk factors (beta = 0.310, p <
      .001). CONCLUSIONS: In health checkup examinees with increased IMT, serum IL-18
      and H. pylori-IgG were independently correlated and were significantly higher
      than in subjects with normal IMT.

PMID- 23121309
TI  - Agreement of drug discovery data with Benford's law.
AB  - The ever-increasing rate of drug discovery data has complicated data analysis and
      potentially compromised data quality due to factors such as data handling errors.
      Parallel to this concern is the rise in blatant scientific misconduct. Combined,
      these problems highlight the importance of developing a method that can be used
      to systematically assess data quality. Benford's law has been used to discover
      data manipulation and data fabrication in various fields. In the authors'
      previous studies, it was demonstrated that the distribution of the corresponding
      activity and solubility data followed Benford's law distribution. It was also
      shown that too intense a selection of training data sets of regression model can
      disrupt Benford's law. Here, the authors present the application of Benford's law
      to a wider range of drug discovery data such as microarray and sequence data.
      They also suggest that Benford's law could also be applied to model building and
      reliability for structure-activity relationship study. Finally, the authors
      propose a protocol based on Benford's law which will provide researchers with an
      efficient method for data quality assessment. However, multifaceted quality
      control such as combinatorial use with data visualization may also be needed to
      further improve its reliability.

PMID- 23121310
TI  - Students' experiences of implementing clinical skills in the real world of
      practice.
AB  - AIMS AND OBJECTIVES: To examine the factors that impact on students'
      implementation of clinical skills in the practice setting. This was a part of a
      larger exploration into the role of the Clinical Skills Laboratory in preparing
      student nurses for clinical practice. BACKGROUND: It is already known that
      students can experience reality shock on clinical placement and that staff
      support is crucial for their adaptation to the environment. This process is
      similar to socialisation theory whereby the newcomer adapts to the workplace.
      DESIGN: A multiple case study design (n = 5) was used. METHODS: Data were
      collected using semi-structured interviews (n = 43) and non-participant
      observation of students implementing skills in clinical practice. RESULTS:
      Findings revealed the factors that could facilitate students' implementation of
      clinical skills were as follows: provision of learning opportunities, staff
      support and supervision, and students' confidence. Factors that hindered students
      were reality shock, 'the gap' in how skills were taught in the higher education
      institutions and the clinical setting, and missed learning opportunities. Support
      from peers in the clinical area and having previous experience of working as a
      health care assistant, or similar, were the factors that could either positively
      or negatively impact on students. CONCLUSIONS: Students need to be adequately
      prepared for the real-life clinical environment. Understanding, through
      socialisation theory, how students adapt to the workplace can facilitate this
      process. Facilitating students' learning includes supporting them, developing
      their confidence and ensuring that they have prior exposure to undertaking
      clinical skills. RELEVANCE TO PRACTICE: Staff working with students in clinical
      practice can help facilitate students' learning and implementing of clinical
      skills through an understanding of how students adapt and 'fit in' to their
      working environment.

PMID- 23121314
TI  - Giant eucalypts - globally unique fire-adapted rain-forest trees?
AB  - CONTENTS: Summary    1 I. Introduction    1 II. Giant eucalypts in a global
      context    2 III. Giant eucalypts - taxonomy and distribution    4 IV. Growth of
      giant eucalypts    6 V. Fire and regeneration of giant eucalypts    8 VI. Are
      giant eucalypts different from other rain-forest trees?    9 VII. Conclusions 10
      Acknowledgements 11 References 11 SUMMARY: Tree species exceeding 70 m in height
      are rare globally. Giant gymnosperms are concentrated near the Pacific coast of
      the USA, while the tallest angiosperms are eucalypts (Eucalyptus spp.) in
      southern and eastern Australia. Giant eucalypts co-occur with rain-forest trees
      in eastern Australia, creating unique vegetation communities comprising fire
      dependent trees above fire-intolerant rain-forest. However, giant eucalypts can
      also tower over shrubby understoreys (e.g. in Western Australia). The local
      abundance of giant eucalypts is controlled by interactions between fire activity
      and landscape setting. Giant eucalypts have features that increase flammability
      (e.g. oil-rich foliage and open crowns) relative to other rain-forest trees but
      it is debatable if these features are adaptations. Probable drivers of eucalypt
      gigantism are intense intra-specific competition following severe fires, and
      inter-specific competition among adult trees. However, we suggest that this was
      made possible by a general capacity of eucalypts for 'hyper-emergence'. We argue
      that, because giant eucalypts occur in rain-forest climates and share traits with
      rain-forest pioneers, they should be regarded as long-lived rain-forest pioneers,
      albeit with a particular dependence on fire for regeneration. These unique
      ecosystems are of high conservation value, following substantial clearing and
      logging over 150 yr.

PMID- 23121313
TI  - Sodium and calcium mechanisms of rhythmic bursting in excitatory neural networks
      of the pre-Botzinger complex: a computational modelling study.
AB  - The neural mechanisms generating rhythmic bursting activity in the mammalian
      brainstem, particularly in the pre-Botzinger complex (pre-BotC), which is
      involved in respiratory rhythm generation, and in the spinal cord (e.g. locomotor
      rhythmic activity) that persist after blockade of synaptic inhibition remain
      poorly understood. Experimental studies in rodent medullary slices containing the
      pre-BotC identified two mechanisms that could potentially contribute to the
      generation of rhythmic bursting: one based on the persistent Na(+) current
      (I(NaP)), and the other involving the voltage-gated Ca(2+) current (I(Ca)) and
      the Ca(2+) -activated nonspecific cation current (I(CAN)), activated by
      intracellular Ca(2+) accumulated from extracellular and intracellular sources.
      However, the involvement and relative roles of these mechanisms in rhythmic
      bursting are still under debate. In this theoretical/modelling study, we
      investigated Na(+)-dependent and Ca(2+)-dependent bursting generated in single
      cells and heterogeneous populations of synaptically interconnected excitatory
      neurons with I(NaP) and I(Ca) randomly distributed within populations. We
      analysed the possible roles of network connections, ionotropic and metabotropic
      synaptic mechanisms, intracellular Ca(2+) release, and the Na(+)/K(+) pump in
      rhythmic bursting generated under different conditions. We show that a
      heterogeneous population of excitatory neurons can operate in different
      oscillatory regimes with bursting dependent on I(NaP) and/or I(CAN), or
      independent of both. We demonstrate that the operating bursting mechanism may
      depend on neuronal excitation, synaptic interactions within the network, and the
      relative expression of particular ionic currents. The existence of multiple
      oscillatory regimes and their state dependence demonstrated in our models may
      explain different rhythmic activities observed in the pre-BotC and other
      brainstem/spinal cord circuits under different experimental conditions.

PMID- 23121315
TI  - Highly selective and sensitive detection of mercuric ion based on a visual
      fluorescence method.
AB  - The instant and on-site detection of trace aqueous mercuric ion still remains a
      challenge for environmental monitoring and protection. This work demonstrates a
      new analytical method and its utility for visual detection of aqueous Hg(2+) on
      the basis of a novel water-soluble CdSe-ZnS quantum dots (QDs) functionalized
      with a bidentate ligand of 2-hydroxyethyldithiocarbamate (HDTC). The fluorescence
      of the aqueous HDTC modified QDs (HDTC-QDs) could be selectively and efficiently
      quenched by Hg(2+) through a surface chelating reaction between HDTC and Hg(2+),
      and the detection limit was measured to be 1 ppb. Most interestingly, the orange
      fluorescence of the HDTC-QDs gradually changes to red upon the increasing amount
      of Hg(2+) added besides the decreasing of the fluorescence intensity. By taking
      advantage of this optical phenomenon, a paper-based sensor for aqueous Hg(2+)
      detection has been developed by immobilizing the HDTC-QDs on cellulose acetate
      paper which has low background fluorescence in the wavelength range. The paper
      based sensor showed high sensitivity and selectivity for Hg(2+) visual detection.
      When Hg(2+) was dropped onto the paper-sensor, an obviously distinguishable
      fluorescence color evolution (from orange to red) could be clearly observed
      depending on the concentration of Hg(2+). The limit of detection of the visual
      method for aqueous Hg(2+) detection was as low as 0.2 ppm. The very simple and
      effective strategy reported here should facilitate the development of portable
      and reliable fluorescence chemosensors for mercuric pollution control.

PMID- 23121316
TI  - Response to Risotto et al.

PMID- 23121317
TI  - Engineering cellular degradation of multilayered capsules through controlled
      cross-linking.
AB  - We report a versatile approach for controlling the intracellular degradation of
      polymer capsules by tailoring the degree of cross-linking in the capsules. Poly(2
      diisopropylaminoethyl methacrylate) capsules were assembled by the layer-by-layer
      technique and covalently stabilized with a redox-responsive bisazide cross-linker
      using click chemistry. The degree of cross-linking, determined using radiation
      scintillation counting, was tuned from 65% to 98% by adjusting the amount of
      cross-linker used to stabilize the polymer films. Transmission electron
      microscopy and fluorescence microscopy studies showed that the pH responsiveness
      of the capsules was maintained, regardless of the degree of cross-linking. Atomic
      force microscopy measurements on planar surfaces revealed that increasing the
      degree of cross-linking decreased the film roughness (from 8.7 to 1.7 nm), hence
      forming smoother films; however the film thicknesses were not significantly
      altered. Cellular studies showed that the rate of intracellular degradation of
      the capsules could be controlled between 0 and 6 h by altering the degree of
      cross-linking in the polymer capsules. These studies also demonstrated that the
      cellular degradation of highly cross-linked capsules (>90%) was significantly
      retarded compared to degradation in simulated cellular conditions. This suggests
      that the naturally occurring cellular reducing environment is rapidly depleted,
      and there is a significant delay before the cells can replenish the reducing
      environment. The modular and versatile nature of this approach lends itself to
      application to a wide range of polymer carriers and thus offers significant
      potential for the design of polymer-based systems for drug and gene delivery.

PMID- 23121318
TI  - Fabrication and characterization of novel antimicrobial films derived from thymol
      loaded zein-sodium caseinate (SC) nanoparticles.
AB  - The objective of this research was to fabricate novel antimicrobial films based
      on zein colloidal nanoparticles coated with sodium caseinate (SC), an
      emulsifier/stabilizer. Thymol-loaded zein-SC nanoparticles were prepared using an
      antisolvent technique, with the average particle size and zeta potential about
      200 +/- 20 nm and -40 mV, respectively. Zein-SC nanoparticle-based films
      exhibited higher mechanical resistance and water barrier capacity than the SC
      films and concomitant good extensibility as compared with zein films. Thymol
      loadings endowed zein-SC nanoparticle-based films with antimicrobial activity
      against  Escherichia coli  and  Salmonella  as well as DPPH radical scavenging
      activity. Water vapor permeability, microstructure, mechanical, and controlled
      release properties of the films were evaluated. The possible relationship between
      some selected physical properties and microstructure were also discussed. Atomic
      force microscopy (AFM) analysis indicated that thymol loadings resulted in the
      emergence phenomena of the nanoparticles to form large particles or packed
      structure, consisting of clusters of nanoparticles, within the film matrix, in a
      thymol loading dependent manner. The appearance of large particles or an
      agglomerate of particles may weaken the compactness of protein network of films
      and thus impair the water barrier capacity, mechanical resistance, and
      extensibility of the films. The release kinetics of thymol from nanoparticle
      based films can be described as a two-step biphasic process, that is, an initial
      burst effect followed by subsequent slower release, and zein-SC nanoparticles
      within the films matrices gave them the ability to sustain the release of thymol.
      In addition, a schematic illustration of the formation pathway of zein-SC
      nanoparticle-based films with or without thymol was proposed to illuminate the
      possible relationship between some selected physical properties and the
      microstructure of the films.

PMID- 23121319
TI  - Energy loss via urine and faeces--a combustive analysis in diabetic rats and the
      impact of antidiabetic treatment on body weight.
AB  - AIMS: Intensive glycaemic control in type 2 diabetes achieved by insulin is
      generally accompanied by body weight gain. This study was performed to emphasize
      the meaning of caloric analysis of urine and faeces for energy balance. METHODS:
      We measured energetic loss via urine and faeces during antihyperglycaemic
      treatment in male obese Zucker diabetic fatty (ZDF) rats. Rats were treated for
      10 days with the sodium-glucose-linked transporter-2 (SGLT2) inhibitor AVE2268,
      with insulin glargine, with the GLP-1 receptor agonist lixisenatide and with the
      combination of insulin glargine and lixisenatide. Each study was accompanied by
      one lean (Fa/?) and one obese (fa/fa) untreated non-diabetic and diabetic control
      group, respectively. Blood glucose, body weight alterations and food assimilation
      efficiency were monitored. RESULTS: In control ZDF rats, more than 12 g/day of
      pure glucose was urinarily excreted. In total, the energetic loss via urine
      exceeded 30% from total energy uptake. Insulin glargine treatment decreased
      urinary energetic loss, leading to a body weight gain of approximately 3 g/day.
      An almost body weight-neutral antihyperglycaemic treatment could be achieved with
      AVE2268 and lixisenatide. While lixisenatide reduced body weight gain via
      reduction of energy uptake, the SGLT2 inhibitor even increased urinary glucose
      and thus energy excretion. Combining insulin glargine with lixisenatide
      attenuated the anabolic effect of insulin resulting in weight neutrality.
      CONCLUSIONS: Our data clearly show renal contribution to the body's energy
      control by urinary glucose excretion (UGE) during antidiabetic treatment. The
      undesired retained energy could be reduced via additional UGE or via simultaneous
      reduction of energy uptake and/or energy retention.

PMID- 23121320
TI  - Sleep stabilizes visuomotor adaptation memory: a functional magnetic resonance
      imaging study.
AB  - The beneficial effect of sleep on motor memory consolidation is well known for
      motor sequence memory, but remains unsettled for visuomotor adaptation in humans.
      The aim of this study was to characterize more clearly the influence of sleep on
      consolidation of visuomotor adaptation using a between-subjects functional
      magnetic resonance imaging (fMRI) design contrasting sleep to total sleep
      deprivation. Our behavioural results, based on seven different parameters, show
      that sleep stabilizes performance whereas sleep deprivation deteriorates it.
      During training, while a set of cerebellar, striatal and cortical areas is
      activated in proportion to performance improvement, the recruitment of the
      hippocampus and frontal cortex protects motor memory against the detrimental
      effects of sleep deprivation. During retest after sleep loss a cerebello-cortical
      network, usually involved in the earliest stage of learning, was recruited to
      perform the task. In contrast, no changes in cerebral activity were observed
      after sleep, suggesting that it may only support the stabilization of the
      visuomotor adaptation memory trace.

PMID- 23121321
TI  - Betamethasone therapy in ataxia telangiectasia: unraveling the rationale of this
      serendipitous observation on the basis of the pathogenesis.
AB  - Ataxia telangiectasia (A-T) is a rare autosomal recessive disorder characterized
      by progressive neurological dysfunction. To date, only supportive care aimed to
      halt the progressive neurodegeneration is available for the treatment. Recently,
      an improvement of neurological signs during short-term treatment with
      betamethasone has been reported. To date, the molecular and biochemical
      mechanisms by which the steroid produces such effects have not yet been
      elucidated. Therefore, a review of the literature was carried out to define the
      potential molecular and functional targets of the steroid effects in A-T.
      Glucocorticoids (GCs) are capable of diffusing into the CNS by crossing the blood
      brain barrier (BBB) where they exert effects on the suppression of inflammation
      or as antioxidant. GCs have been shown to protect post-mitotic neurons from
      apoptosis. Eventually, GCs may also modulate synaptic plasticity. A better
      understanding of the mechanisms of action of GCs in the brain is needed, because
      in A-T during the initial phase of cell loss the neurological impairment may be
      rescued by interfering in the biochemical pathways. This would open a new window
      of intervention in this so far incurable disease.

PMID- 23121322
TI  - Tracheal intubation with a camera embedded in the tube tip (Vivasight(TM) ).
AB  - We studied tracheal intubation in manikins and patients with a camera embedded in
      the tip of the tracheal tube (Vivasight(TM) ). Four people in two teams and two
      individuals attempted intubation of a manikin through an i-gel(TM)  10 times
      each. The tracheas of 12 patients with a Mallampati grade of 1 were intubated
      with a Vivasight tracheal tube through a Berman airway, passed over a Frova(TM) 
      introducer. All 60 manikin intubations were successful, taking a mean (SD) time
      of 1.4 (0.5) s. The fastest intubation was performed in 0.5 s. All 12
      participants' tracheas were successfully intubated in a median (IQR [range]) time
      of 90 (70-120 [50-210]) s. Seven participants complained of a sore throat,
      comparable with earlier findings for standard laryngoscopy and intubation: five
      mild; one moderate; and one severe. Tracheal intubation with the Vivasight
      through the i-gel or Berman airway is an alternative to existing techniques,
      against which it should be compared in randomised controlled trials in human
      participants. It has potential as a fast airway rescue technique.

PMID- 23121324
TI  - Compelling evidence for coronary-bypass surgery in patients with diabetes.

PMID- 23121325
TI  - Solvent optimization for anthocyanin extraction from Syzygium cumini L. Skeels
      using response surface methodology.
AB  - Anthocyanins are plant pigments that are potential candidates for use as natural
      food colourant. In this study, Syzygium cumini fruit skin has been used as
      anthocyanin source. All the six major types of anthocyanins were identified in
      the sample by ultra performance liquid chromatography studies, and the
      antioxidant activity was found to be 4.34 +/- 0.26 Fe(2+)g(- 1) in the sample
      with highest anthocyanin content. Optimization of conditions for extracting high
      amounts of anthocyanin from the fruit peels was investigated by response surface
      methodology. The results suggested that highest anthocyanin yield (763.80 mg; 100
      ml(- 1)), highest chroma and hue angle in the red colour range could be obtained
      when 20% ethanol was used in combination with 1% acetic acid. Methanol was
      replaced with ethanol for the extraction of pigments due to its less toxicity and
      being safe for human consumption. The optimized solvent can be used to extract
      anthocyanins from the S. cumini fruits and used as natural colourants in the food
      industries.

PMID- 23121326
TI  - The insulin-like growth factor-1 gene is associated with cerebral infarction in
      Japanese subjects.
AB  - Atherosclerosis leads to cerebral infarction (CI) and the insulin/insulin-like
      growth factor-1 (IGF1) signaling pathway plays an important role in this process
      during adult life. The purpose of this study was to investigate the relationship
      between the human IGF1 gene and CI in the Japanese population via a case-control
      study that also included a separate analysis of the two gender groups. A total of
      155 CI patients and 316 controls were genotyped for six single nucleotide
      polymorphisms (SNPs) of the human IGF1 gene (rs2162679, rs7956547, rs2288378,
      rs2072592, rs978458 and rs6218). All data were analyzed for three separate
      groups: the total subjects, men and women. The logistic regression analysis
      revealed that the GG + AG variant of rs2162679 (P = 0.047), the AA + GA variant
      of rs2072592 (P = 0.005) and the CC + TC variant of rs6218 (P = 0.015) exhibited
      a protective effect for CI in the total subject group. For the women and the
      total subjects groups, the overall distribution of the haplotype established by
      rs7956547-rs978458 was significantly different between the CI patients and the
      non-CI subjects. For the total subjects, the frequency of the T-G haplotype
      (rs7956547-rs978458) was also significantly higher (P = 0.034), whereas the
      frequency of the T-A haplotype (rs7956547-rs978458) was significantly lower (P =
      0.008) in the CI patients versus the non-CI subjects. For women, the frequency of
      the T-A haplotype (rs7956547-rs978458) was significantly lower (P = 0.021) in the
      CI patients as compared with the non-CI subjects. The specific SNPs and
      haplotypes can be utilized as genetic markers for CI resistance or CI risk.

PMID- 23121327
TI  - Relative efficiency of morphological characters and molecular markers in the
      establishment of an apricot core collection.
AB  - In order to optimize the management of genetic resources, in most cases a
      representative sample of the germplasm collections needs to be developed. The
      establishment of a core collection is thus of major importance either to minimize
      the cost associated with the management of the associated germplasm or to apply
      analysis onto representative bases. In order to select a representative core
      collection among the Tunisian apricot germplasm of 110 accessions large, the
      Maximization strategy algorithm was used. This algorithm was shown to be the most
      convenient when using both morphological traits and molecular markers. Three core
      collections based on morphological characters, molecular markers or the combined
      data were compared. Our data indicate that both the molecular and the
      morphological markers have to be considered to obtain a core collection that
      represents the global diversity of the 110 accessions. Using this method, a
      subset of 34 selected accessions was found to represent accurately the 110
      accessions present in the whole collection (75 to 100% for the morphological
      characters and 97% of the molecular markers). These results show that the
      combination of molecular and morphological markers is an efficient way to
      characterize the apricot core collection and provides an exhaustive coverage for
      the analyzed diversity on morphological and genetic bases.

PMID- 23121328
TI  - Phenolic antioxidant 2,6-di-tert-butyl-p-cresol (vitamin E synthetic analogue)
      does not inhibit 1,1'-dimetyl-4,4'-bipyridium dichloride (paraquat)-induced
      structural chromosomal damage in cultured leukocytes of the dark-spotted-frog
      Pelophylax (Rana) nigromaculatus.
AB  - Pro-oxidative effect of phenolic antioxidant (vitamin E) in combination with the
      initiators on human low-density lipoprotein is known. Recently I reported that
      oxidative stress induced by vitamin E in combination with the herbicide paraquat
      enhances structural chromosomal damage in cultured anuran leukocytes. In the
      present study, the phenolic antioxidant vitamin E-synthetic-analogue 2,6-di-tert
      butyl-p-cresol (BHT) in combination with paraquat was found to enhance structural
      chromosomal damage in cultured Pelophylax (Rana) nigromaculatus leukocytes more
      than paraquat only and paraquat plus nicotinamido adenine dinucleotido phosphate
      served as positive control, although BHT only had no effect on induction of
      structural chromosomal damage. Paraquat plus BHT-enhanced structural chromosomal
      damage was inhibited by combination of the superoxide dismutase mimic
      Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin and the hydrogen peroxide scavenger
      catalase. In test based on reduction of paraquat cation, BHT was found to reduce
      paraquat cation chemically to paraquat monocation radical. These results suggest
      that BHT functions in chemically donating electron to paraquat and thereby
      induces an acute accumulation of reactive oxygen species, resulting in increase
      in chromosomal damage.

PMID- 23121329
TI  - Haplotype of smoothelin gene associated with essential hypertension.
AB  - Smoothelin is a specific cytoskeletal protein that is associated with smooth
      muscle cells. The human SMTN gene encodes smoothelin-A and smoothelin-B, and
      studies using SMTN gene knockout mice have demonstrated that these animals
      develop hypertension. The aim of the present study was to investigate the
      association between the human SMTN gene and essential hypertension (EH) using a
      haplotype-based case-control study. This is the first study to assess the
      association between essential hypertension and this gene. A total of 255 EH
      patients and 225 controls were genotyped for the five single-nucleotide
      polymorphisms (rs2074738, rs5997872, rs56095120, rs9621187 and rs10304) used as
      genetic markers for the human SMTN gene. Data were analyzed for three separate
      groups: total subjects, men and women. Although there were no differences for
      genotype distributions, or the dominant and recessive model distributions noted
      for total subjects, men and women for all of the SNPs selected for the present
      study, for the total subjects group, the frequency of the G-C-A-C haplotype
      constructed with rs2074738-rs5997872-rs56095120-rs9621187 was significantly lower
      in the essential hypertension patients than in the controls (P = 0.002). The G-C
      A-C haplotype appears to be a useful protective marker of essential hypertension
      in Japanese, and the SMTN gene might also be a genetic marker for essential
      hypertension.

PMID- 23121330
TI  - Dorso-ventral axis formation of the Drosophila oocyte requires Cyclin G.
AB  - In general, cyclins control the cell cycle. Not so the atypical cyclins, which
      are required for diverse cellular functions such as for genome stability or for
      the regulation of transcription and translation. The atypical Cyclin G (CycG)
      gene of Drosophila has been involved in the epigenetic regulation of abdominal
      segmentation, cell proliferation and growth, based on overexpression and RNAi
      studies, but detailed analyses were hampered by the lack of a cycG mutant. For
      further investigations, we subjected the cycG locus to a detailed molecular
      analysis. Moreover, we studied a cycG null mutant that we recently established.
      The mutant flies are homozygous viable, however, the mutant females are sterile
      and produce ventralized eggs. Here we show that this egg phenotype is primarily a
      consequence of a defective Epidermal Growth Factor Receptor (EGFR) signalling
      pathway. By using different read outs, we demonstrate that cycG loss is
      tantamount to lowered EGFR signalling. Inferred from epistasis experiments, we
      conclude that CycG promotes the Grk signal in the oocyte. Abnormal accumulation
      but regular secretion of the Grk protein suggests defects of Grk translation in
      cycG mutants rather than transcriptional regulation. Accordingly, protein
      accumulation of Vasa, which acts as an oocyte specific translational regulator of
      Grk in the oocyte is abnormal. We propose a role of cycG in processes that
      regulate translation of Grk and hence, influence EGFR-mediated patterning
      processes during oogenesis.

PMID- 23121331
TI  - Employee recruitment.
AB  - The way an organization recruits can influence the type of employees it hires,
      how they perform, and their retention rate. This article provides a selective
      review of research that has addressed recruitment targeting, recruitment methods,
      the recruitment message, recruiters, the organizational site visit, the job
      offer, and the timing of recruitment actions. These and other topics (e.g., the
      job applicant's perspective) are discussed in terms of their potential influence
      on prehire (e.g., the quality of job applicants) and posthire (e.g., new employee
      retention) recruitment outcomes. In reviewing research, attention is given to the
      current state of scientific knowledge, limitations of previous research, and
      important issues meriting future investigation.

PMID- 23121332
TI  - Lymphosarcoma in a captive bonnethead shark, Sphyrna tiburo (L.).

PMID- 23121333
TI  - What is your diagnosis? Corneal scraping from an ulcerative lesion in a Quarter
      horse.

PMID- 23121334
TI  - The preclinical profile of asenapine: clinical relevance for the treatment of
      schizophrenia and bipolar mania.
AB  - INTRODUCTION: Asenapine is a novel antipsychotic drug approved for the treatment
      of acute schizophrenia, manic, or mixed episodes associated with bipolar I
      disorder, as a maintenance treatment of schizophrenia and as an adjunctive
      therapy with lithium or valproate for the acute treatment of manic or mixed
      episodes associated with bipolar I disorder in adults. AREAS COVERED: This review
      focuses on the preclinical profile of asenapine. It analyzes the pharmacological,
      neurochemical, behavioral, and molecular mechanisms of asenapine and their
      contribution to the beneficial therapeutic advantages of the drug as reported in
      published preclinical and clinical studies, product labels, and poster
      presentations. EXPERT OPINION: Asenapine exhibits a broad pharmacological profile
      that targets a wide range of neurotransmitter receptors with variable affinities.
      The drug preferentially increases dopamine, norepinephrine, and acetylcholine
      levels in cortical and limbic brain areas. It also potentiates cortical
      glutamatergic neurotransmission, and is active in behavioral animal models
      predictive of antipsychotic, antidepressant, and pro-cognitive activities.
      Chronic administration of asenapine alters the abundance of dopamine, serotonin,
      glutamate, adrenergic, and cholinergic receptor subtypes in different brain
      regions. These action mechanisms of asenapine might contribute to its unique
      psychopharmacological properties in the improved treatment of schizophrenia and
      other psychotic disorders.

PMID- 23121335
TI  - Hydrogen water consumption prevents osteopenia in ovariectomized rats.
AB  - BACKGROUND AND PURPOSE: Accumulating evidence indicates an important role of
      oxidative stress in the progression of osteoporosis. Recently, it was
      demonstrated that hydrogen gas, as a novel antioxidant, could selectively reduce
      hydroxyl radicals and peroxynitrite anion to exert potent therapeutic antioxidant
      activity. The aim of the present work was to investigate the effect of hydrogen
      water (HW) consumption on ovariectomy-induced osteoporosis. EXPERIMENTAL
      APPROACH: Ovariectomized rats were fed with HW (1.3 +/- 0.2 mg.L-1) for 3 months.
      Then, blood was collected and femur and vertebrae were removed for evaluation of
      the effect of HW on bone. KEY RESULTS: HW consumption in ovariectomized rats had
      no significant effect on oestrogen production, but prevented the reduction of
      bone mass including bone mineral content and bone mineral density in femur and
      vertebrae, and preserved mechanical strength including ultimate load, stiffness,
      and energy, and bone structure including trabecular bone volume fraction,
      trabecular number, and trabecular thickness in femur, and preserved mechanical
      strength including ultimate load and stiffness, and bone structure including
      trabecular bone volume fraction and trabecular number in vertebrae. In addition,
      treatment with HW abated oxidative stress and suppressed IL-6 and TNF-alpha mRNA
      expressions in femur of ovariectomized rats; treatment with HW increased femur
      endothelial NOS activity and enhanced circulating NO level in ovariectomized
      rats. CONCLUSIONS AND IMPLICATIONS: HW consumption prevents osteopenia in
      ovariectomized rats possibly through the ablation of oxidative stress induced by
      oestrogen withdrawal.

PMID- 23121336
TI  - Caregiving, single parents and cumulative stresses when caring for a child with
      cancer.
AB  - BACKGROUND: Single parents whose children have cancer are a marginalized group
      who report less family centred care, and therefore, less quality cancer care for
      their children. As such, the aims of this study were to explore how single
      parents of children with cancer describe their caregiving experiences and to
      understand their contextual life stressors. METHODS: A constructivist grounded
      theory method was used. Qualitative interviews with 29 single parents of children
      with cancer who were at least 6 months post-diagnosis were recruited between
      November 2009 and April 2011 from four hospitals across Canada. Line-by-line
      coding was used to establish codes and themes and constant comparison was used to
      establish relationships among emerging codes and conceptual themes. RESULTS: The
      first set of findings report on caregiving duties including: emotional tasks,
      informational tasks and physical tasks. The second set of findings report on the
      contextual picture of parent's lives including their living conditions, their
      physical and mental health and their family histories of disruption, trauma and
      disease. CONCLUSIONS: Single parents caring for children with cancer were found
      to experience several cumulative stressors in addition to the current strain of
      caring for a child with cancer. The synergy of these cumulative stresses with the
      added strain of caregiving for a child with cancer may have long-term health and
      financial implications for parents. Broad-based policy interventions should focus
      on relieving the chronic strains associated with being a single parent of a child
      with cancer.

PMID- 23121338
TI  - Comparison of hybrid and sequential therapies for Helicobacter pylori eradication
      in Iran: a prospective randomized trial.
AB  - BACKGROUND: The eradication of Helicobacter pylori has been always a concern. In
      the present study, we aimed to compare two novel treatments in Iran. METHOD: Four
      hundred and twenty patients with peptic ulcer and naive H. pylori infection were
      randomized in the study. Two hundred and ten patients received hybrid therapy:
      pantoprazole 40 mg/b.i.d. and amoxicillin 1 g/b.i.d. for 14 days plus 500 mg
      clarithromycin and 500 mg tinidazole, both twice daily for the last 7 days. The
      other 210 patients received sequential therapy: 40 mg pantoprazole/b.i.d. for 10
      days and 1 g amoxicillin/b.i.d. for the first 5 days, followed by 500 mg
      clarithromycin/b.i.d. and 500 mg tinidazole/b.i.d. for the last 5 days. C14-urea
      breath test was performed 8 weeks after the treatment. RESULTS: Three hundred and
      ninety-six patients (197 patients in the hybrid group and 199 patients in the
      sequential group) completed the study. The compliance rates were 96.7 and 98.6%
      for the two groups, respectively. The intention-to-treat eradication rate was
      89.5% (95% CI = 85.4-93.6) for the hybrid group and 76.7% (95% CI = 71-82.4) for
      the sequential group (p = .001), and the per-protocol eradication rates were
      92.9% (95% CI = 89.2-96.5) and 79.9% (95% CI = 74.1-85.4) for the hybrid and
      sequential groups (p = .001), respectively. Severe adverse effects were observed
      in 2.4% of patients in the hybrid group and 3.8% of those in the sequential
      group. CONCLUSION: According to our results, sequential regimen does not seem to
      be an appropriate therapy for H. pylori eradication in the Iranian population,
      whereas hybrid therapy showed to be more effective. However, considering the high
      cost of clarithromycin in Iran, we recommend further studies to compare hybrid
      therapy with bismuth-containing regimens or to assess the effects of hybrid
      therapies with periods shorter than 14 days.

PMID- 23121340
TI  - Aerodynamic drag is not the major determinant of performance during giant slalom
      skiing at the elite level.
AB  - This investigation was designed to (a) develop an individualized mechanical model
      for measuring aerodynamic drag (F(d) ) while ski racing through multiple gates,
      (b) estimate energy dissipation (E(d) ) caused by F(d) and compare this to the
      total energy loss (E(t) ), and (c) investigate the relative contribution of E(d)
      /E(t) to performance during giant slalom skiing (GS). Nine elite skiers were
      monitored in different positions and with different wind velocities in a wind
      tunnel, as well as during GS and straight downhill skiing employing a Global
      Navigation Satellite System. On the basis of the wind tunnel measurements, a
      linear regression model of drag coefficient multiplied by cross-sectional area as
      a function of shoulder height was established for each skier (r > 0.94, all P <
      0.001). Skiing velocity, F(d) , E(t) , and E(d) per GS turn were 15-21 m/s, 20-60
      N, -11 to -5 kJ, and -2.3 to -0.5 kJ, respectively. E(d) /E(t) ranged from ~5% to
      28% and the relationship between E(t) /v(in) and E(d) was r = -0.12 (all NS). In
      conclusion, (a) F(d) during alpine skiing was calculated by mechanical modeling,
      (b) E(d) made a relatively small contribution to E(t) , and (c) higher relative
      E(d) was correlated to better performance in elite GS skiers, suggesting that
      reducing ski-snow friction can improve this performance.

PMID- 23121339
TI  - Exercise-induced stress resistance is independent of exercise controllability and
      the medial prefrontal cortex.
AB  - Exercise increases resistance against stress-related disorders such as anxiety
      and depression. Similarly, the perception of control is a powerful predictor of
      neurochemical and behavioral responses to stress, but whether the experience of
      choosing to exercise, and exerting control over that exercise, is a critical
      factor in producing exercise-induced stress resistance is unknown. The current
      studies investigated whether the protective effects of exercise against the
      anxiety- and depression-like consequences of stress are dependent on exercise
      controllability and a brain region implicated in the protective effects of
      controllable experiences, the medial prefrontal cortex. Adult male Fischer 344
      rats remained sedentary, were forced to run on treadmills or motorised running
      wheels, or had voluntary access to wheels for 6 weeks. Three weeks after exercise
      onset, rats received sham surgery or excitotoxic lesions of the medial prefrontal
      cortex. Rats were exposed to home cage or uncontrollable tail shock treatment
      three weeks later. Shock-elicited fear conditioning and shuttle box escape
      testing occurred the next day. Both forced and voluntary wheel running, but not
      treadmill training, prevented the exaggerated fear conditioning and interference
      with escape learning produced by uncontrollable stress. Lesions of the medial
      prefrontal cortex failed to eliminate the protective effects of forced or
      voluntary wheel running. These data suggest that exercise controllability and the
      medial prefrontal cortex are not critical factors in conferring the protective
      effects of exercise against the affective consequences of stressor exposure, and
      imply that exercise perceived as forced may still benefit affect and mental
      health.

PMID- 23121342
TI  - Interrater agreement, reliability and validity of the Glamorgan Paediatric
      Pressure Ulcer Risk Assessment Scale.
AB  - AIMS AND OBJECTIVES: To determine (1) What is the degree of interrater agreement
      and reliability of Glamorgan scale item and sum scores? and (2) Are Glamorgan
      scale sum scores valid? BACKGROUND: Pressure ulcer risk assessment scales are
      recommended for use in clinical practice. For paediatric patients, 12 instruments
      are currently described. Empirical evidence about the performance of Glamorgan
      scale scores in clinical practice is limited. DESIGN: An observational validation
      study was conducted on a paediatric cardiac unit of a large university hospital
      in Germany in April and May 2010. METHODS: Children were assessed simultaneously
      and independently by varying convenience samples of three nurses per assessment
      situation. Pressure ulcer risk was measured by the Glamorgan scale and a 100 mm
      Visual Analogue Scale (VAS). Proportions of agreement (po ), multirater kappa and
      intraclass correlation coefficients were calculated. RESULTS: Thirty children
      were rated by 27 nurses. Median children's age was 5.5 years. Agreement among
      item scores was high, whereas reliability coefficients of item scores were low.
      Interrater reliability for the Glamorgan scale sum scores was higher than for VAS
      scores. Correlation between both scales was moderate. CONCLUSIONS: High agreement
      among item scores indicates that nurses are able to make precise judgements. The
      low interrater reliability of item and sum scores indicates that nurses were
      unable to differentiate the rated children based on their item and sum scores,
      thus providing little additional clinical relevant information about pressure
      ulcer risk in this setting. RELEVANCE TO CLINICAL PRACTICE: The Glamorgan scale
      and the VAS are unable to make clear distinctions in a low-risk setting.
      Therefore, it is unlikely that the tools in this setting provide additional
      information for clinical decision making. Both tools are not recommended for
      daily use.

PMID- 23121341
TI  - Highly efficient binding of paramagnetic beads bioconjugated with 100,000 or more
      antibodies to protein-coated surfaces.
AB  - We report here the first kinetic characterization of 1 MUm diameter
      superparamagnetic particles (MP) decorated with over 100,000 antibodies binding
      to protein antigens attached to flat surfaces. Surface plasmon resonance (SPR)
      was used to show that these antibody-derivatized MPs (MP-Ab(2)) exhibit
      irreversible binding with 100-fold increased association rates compared to free
      antibodies. The estimated upper limit for the dissociation constant of MP-Ab(2)
      from the SPR sensor surface is 5 fM, compared to 3-8 nM for the free antibodies.
      These results are explained by up to 2000 interactions of MP-Ab(2) with protein
      decorated surfaces. Findings are consistent with highly efficient capture of
      protein antigens in solution by the MP-Ab(2) and explain in part the utility of
      these beads for ultrasensitive protein detection into the fM and aM range.
      Aggregation of these particles on the SPR chip, probably due to residual magnetic
      microdomains in the particles, also contributes to ultrasensitive detection and
      may also help drive the irreversible binding.

PMID- 23121343
TI  - Dietary intake data collection: challenges and limitations.
AB  - The purpose of this paper is to succinctly review the origin of US dietary
      surveys, the challenges and limitations of obtaining dietary intake data, the
      National Nutrition Monitoring and Related Research Act of 1990, the integrated US
      federal food survey, and the development of the US Department of Agriculture's
      (USDA) automated multiple-pass method. The USDA has monitored the food
      consumption patterns of Americans since the late 1890 s. In 2002, the US
      Department of Health and Human Services and the USDA integrated their data
      collection efforts, with data now collected on a continuous basis. Two 24-hour
      dietary recalls are obtained using USDA's automated multiple-pass method. By
      combining their respective areas of expertise, the USDA and the Department of
      Health and Human Services have increased research opportunities for scientists
      and provided data foundational for establishing programs and public policy.

PMID- 23121344
TI  - Fluid intake of adults in four Chinese cities.
AB  - To investigate the fluid intake and knowledge on water and health in Chinese
      adults, and to provide a scientific basis for the development of adequate water
      intake values for people in China. A total of 1,483 adults aged 18-60 years were
      selected from four provincial capital cities using a multiple-stage random
      sampling method. The information on the amounts and types of daily fluid intake
      was collected using a 24-h fluid intake record for 7 consecutive days. Trained
      interviewers used a questionnaire to assess knowledge on water. The median of
      daily total fluid intake was 1,488 mL, with a wide range from 86 mL to 7,036 mL.
      Significant differences were found for fluid intake among the four cities. The
      medians of daily intakes of plain water, tea, and beverages were 786 mL, 109 mL,
      and 186 mL, respectively. Approximately 32% of the subjects drank less water than
      the amount recommended by the Chinese Nutrition Society (1,200 mL/day) and 71.6%
      of participants lacked knowledge of these recommendations. Moreover, 48.3% of
      them drank water only when they felt thirsty.

PMID- 23121345
TI  - Beverages and body weight: challenges in the evidence-based review process of the
      Carbohydrate Subcommittee from the 2010 Dietary Guidelines Advisory Committee.
AB  - Concern about the role of beverages, especially those containing sugar, in the
      obesity epidemic continues to escalate. Bans on sugar-sweetened beverages and
      chocolate milk have expanded from the school cafeteria to the ballpark and
      convenience store. This review describes the experience of the 2010 Dietary
      Guidelines Advisory Committee (DGAC) in conducting an evidence-based review of
      dietary exposure and health outcomes. The following four topics relevant to
      fluids and body weight were reviewed: added sugar, noncaloric sweeteners, food
      form and body weight, and macronutrients and satiety. There were limited and
      conflicting data on how liquids and solids affect energy intake and body weight.
      Fluid intake is typically not tracked in prospective, cohort longitudinal
      studies; thus, data are not available on fluid intake and health status from
      studies using the strongest epidemiologic designs. Despite public perception that
      beverages are linked to increased body weight compared with whole foods, evidence
      based reviews of this topic do not support that liquid calories are processed
      differently in the body. The practical recommendation to replace caloric
      beverages with water as an aid to control weight is based on calorie reduction,
      rather than a link between added-sugar intake and obesity.

PMID- 23121346
TI  - Challenges of linking chronic dehydration and fluid consumption to health
      outcomes.
AB  - The purpose of this article is to review the effects of chronic mild dehydration
      and fluid consumption on specific health outcomes including obesity. The
      electronic databases PubMed and Google Scholar were searched for relevant
      literature published from the time of their inception to 2011, with results
      restricted to studies performed on human subjects and reports in the English
      language. Key words included the following: dehydration, hypohydration, water
      intake, fluid intake, disease, and the names of specific disease states. Strength
      of evidence categories were described for 1) medical conditions associated with
      chronic dehydration or low daily water intake, and 2) randomized-controlled
      trials regarding the effects of increased water consumption on caloric intake,
      weight gain, and satiety. This process determined that urolithiasis is the only
      disorder that has been consistently associated (i.e., 11 of 13 publications) with
      chronic low daily water intake. Regarding obesity and type 2 diabetes, evidence
      suggests that increased water intake may reduce caloric intake for some
      individuals. Recommendations for future investigations include measuring total
      fluid intake (water + beverages + water in solid food), conducting randomized
      controlled experiments, identifying novel hydration biomarkers, and delineating
      hydration categories.

PMID- 23121347
TI  - Investigating the associations between hydration and exercise performance:
      methodology and limitations.
AB  - Loss of body water, if sufficiently severe, impairs most physiological functions,
      but the body water content fluctuates over the course of a normal day with no
      implications for physical or mental performance. The point at which an effect of
      dehydration becomes apparent has been the subject of much debate, in part, at
      least, because of the different tests that have been applied, differences in the
      methodologies used to induce dehydration and also because of differences in the
      fitness and other physiological characteristics of the subjects studied. The act
      of drinking itself and the conscious denial of access to water will also have
      implications for subjective responses to the exercise task. In many published
      studies, it is difficult to separate the effects of ingestion of water from those
      of carbohydrate, electrolytes, and other drink components. Nevertheless, there is
      good evidence that drinking appropriate amounts of water, especially cold water,
      can enhance exercise performance in many situations.

PMID- 23121348
TI  - Dehydration and endurance performance in competitive athletes.
AB  - The field of research examining the link between dehydration and endurance
      performance is at the dawn of a new era. This article reviews the latest findings
      describing the relationship between exercise-induced dehydration and endurance
      performance and provides the knowledge necessary for competitive, endurance
      trained athletes to develop a winning hydration strategy. Acute, pre-exercise
      body weight loss at or above 3% may decrease subsequent endurance performance.
      Therefore, endurance athletes should strive to start exercise well hydrated,
      which can be achieved by keeping thirst sensation low and urine color pale and
      drinking approximately 5-10 mL/kg body weight of water 2 h before exercise.
      During exercise lasting 1 h or less, dehydration does not decrease endurance
      performance, but athletes are encouraged to mouth-rinse with sports drinks.
      During exercise lasting longer than 1 h, in which fluid is readily available,
      drinking according to the dictates of thirst maximizes endurance performance. In
      athletes whose thirst sensation is untrustworthy or when external factors such as
      psychological stress or repeated food intake may blunt thirst sensation, it is
      recommended to program fluid intake to maintain exercise-induced body weight loss
      around 2% to 3%.

PMID- 23121349
TI  - Hydration for recreational sport and physical activity.
AB  - This review presents recommendations for fluid needs and hydration assessment for
      recreational activity. Fluid needs are based on sweat losses, dependent on
      intensity and duration of the activity, and will vary among individuals.
      Prolonged aerobic activity is adversely influenced by dehydration, and heat
      exposure will magnify this effect. Fluid needs predicted for running 5-42 km at
      recreational paces show that fluid losses are <2% body mass; thus, aggressive
      fluid replacement may not be necessary. Competitive paces result in greater fluid
      losses and greater fluid needs. Fluid needs for recreational activity may be low;
      however, carbohydrate consumption (sport drinks, gels, bars) can benefit high
      intensity (<= 1 h) and less-intense, long-duration activity (>= 1 h). Spot
      measures of urine color or urine-specific gravity to assess hydration status have
      limitations. First morning urine concentration and body mass with gross thirst
      perception can be simple ways to assess hydration status.

PMID- 23121350
TI  - Methods for assessing the effects of dehydration on cognitive function.
AB  - Studying the effects of dehydration on cognitive function presents a variety of
      unique and difficult challenges to investigators. These challenges, which are
      addressed in this article, can be divided into three general categories: 1)
      choosing an appropriate method of generating a consistent level of dehydration;
      2) determining and effectively employing appropriate and sensitive measures of
      cognitive state; and 3) adequately controlling the many confounding factors that
      interfere with assessment of cognitive function. The design and conduct of
      studies on the effects of dehydration on cognitive function should carefully
      consider various methodological issues, and investigators should carefully weigh
      the benefits and disadvantages of particular methods and procedures.

PMID- 23121351
TI  - Thirst and hydration status in everyday life.
AB  - Water is an essential nutrient for all persons; thus, maintaining a chronic state
      of optimal hydration is recognized to provide health benefits. Fluid balance is
      maintained via thirst, a feedback-controlled variable, regulated acutely by
      central and peripheral mechanisms. However, voluntary drinking is also a behavior
      influenced by numerous social and psychological cues. Therefore, whether "thirst
      guided" drinking maintains optimal hydration status is a multifactorial issue.
      Thirst perception is typically assessed by subjective ratings using either
      categorical or visual analog scales; however, which instrument yields greater
      sensitivity to change in hydration status has not been examined. Ratings of
      thirst perception do not always yield predictable patterns of voluntary drinking
      following dehydration; therefore, perceived thirst and ad libitum drinking are
      not equivalent measures of human thirst. The recommendation "drink to thirst" is
      frequently given to healthy individuals during daily life. However, factors and
      conditions (e.g., age, disease) that influence thirst should be recognized and
      probed further.

PMID- 23121352
TI  - Hydration, morbidity, and mortality in vulnerable populations.
AB  - Both acute and chronic fluid deficits have been shown to be associated with a
      number of adverse health outcomes. At the extreme, deprivation of water for more
      than a few days inevitably leads to death, but even modest fluid deficits may
      precipitate adverse events, especially in young children, in the frail elderly
      and in those with poor health. Epidemiological studies have shown an association,
      although not necessarily a causal one, between a low habitual fluid intake and
      some chronic diseases, including urolithiasis, constipation, asthma,
      cardiovascular disease, diabetic hyperglycemia, and some cancers. Acute
      hypohydration may be a precipitating factor in a number of acute medical
      conditions in elderly persons. Increased mortality, especially in vulnerable
      populations, is commonly observed during periods of abnormally warm weather, with
      at least part of this effect due to failure to increase water intake, and this
      may have some important implications for those responsible for forward planning
      in healthcare facilities.

PMID- 23121353
TI  - Global patterns of water intake: how intake data affect recommendations.
AB  - Studies to assess water intake have been undertaken in many countries around the
      world. Some of these have been large-scale studies, whereas others have used a
      small number of subjects. These studies provide an emerging picture of water
      and/or fluid consumption in different populations around the world. Studies of
      this nature have also formed the basis of a number of recommendations published
      by different organizations, including the US Institute of Medicine and the
      European Food Safety Authority. The results of these intake studies indicate
      substantial differences in water and/or fluid intake in different populations,
      which have translated into different intake recommendations.

PMID- 23121354
TI  - Developing the evidence base for addressing inequalities and smoking in the
      United Kingdom.
AB  - AIMS: Smoking is an increasing cause of health inequalities in high-income
      countries. This supplement describes pilot projects set up in England to develop
      and test pathways to ensure that disadvantaged groups, where smoking is
      frequently the norm, are reached, encouraged and supported to stop their tobacco
      use. Target groups were: smokers attending centres set up for highly deprived
      parents; smokers with serious and enduring mental illness; pregnant smokers;
      prisoners/other offenders who smoked; South Asian tobacco chewers; and recent
      quitters from 'routine and manual' occupational groups. METHODS: Commonalities
      observed across the six projects are summarized, alongside recommendations for
      implementation. RESULTS: A significant barrier to implementation was the lack of
      mandatory identification of tobacco users across primary, secondary and community
      health-care settings and routine use of expired air carbon monoxide monitoring,
      particularly for high-risk groups. Appropriate use of financial incentives and
      national guidance is probably necessary to achieve both this and the adoption of
      'joined-up' tobacco dependence treatment pathways for these target groups.
      Further research is needed on the impact of 'opt out' pathways: while resulting
      in increased referral rates, success rates were lower. In general, smoking
      cessation service targets were a barrier to implementation. Flexibility and
      tailoring of interventions were required and most projects trained those already
      working in relevant settings, given their greater understanding of target groups.
      Mandatory training of all frontline health-care staff was deemed desirable.
      CONCLUSIONS: Implementing the findings of these projects will require resources,
      for training, incentivizing health-care workers and further research. However,
      continuing with the status quo may result in sustained tobacco use health
      inequalities for the foreseeable future.

PMID- 23121355
TI  - Evaluation of a programme to increase referrals to stop-smoking services using
      Children's Centres and smoke-free families schemes.
AB  - AIMS: To assess the feasibility and effectiveness of a new service using referral
      liaison advisers to increase the number of referrals of parents/carers at
      selected Children's Centres to National Health Service (NHS) Stop Smoking
      Services (SSS) and/or smoke-free families schemes (SFS). DESIGN: This mixed
      methods pilot study collected numerical data on indicators of smoking behaviours
      and carried out face-to-face and telephone interviews. SETTINGS: Thirteen
      Children's Centres in Liverpool and Nottingham using local providers of smoking
      cessation services, from September 2010 to April 2011. PARTICIPANTS: Parents and
      carers registered with, and staff working for, Children's Centres. MEASURES:
      Number of smokers referred to smoking cessation services and/or smoke-free family
      schemes and the views of service providers and users on the new service.
      FINDINGS: In Liverpool, 181 referrals to NHS SSS were made from 331 identified
      smokers (54.7%); extrapolated to 12 months, this represents a 182% increase in
      referrals from baseline and a similar extrapolation indicates a 643% increase
      from baseline of referrals to smoke-free families schemes. There were no reliable
      baseline data for Nottingham; 31 referrals were made (30.7% of smokers) to SSS
      and 44 referrals to SFS from 52 contacts (84.6%). The interviews highlighted the
      need for sustained personal contact with parents/carers to discuss smoking
      behaviours and concerns and their willingness to be referred to SFS as part of
      caring for their child. CONCLUSIONS: Routine recording of smoking status and
      appropriate follow-up by trained staff in Children's Centres can lead to
      significant numbers of clients attending stop-smoking services, although
      relatively few stop smoking.

PMID- 23121356
TI  - Tailored tobacco dependence support for mental health patients: a model for
      inpatient and community services.
AB  - AIMS: Although smoking prevalence among people with severe mental illness is
      high, it remains largely unaddressed. This pragmatic pilot project aimed to
      develop and implement a tailored tobacco dependence service in mental health
      settings and to assess its impact, as well as barriers and facilitators to
      implementation. DESIGN: An integrative service model, spanning acute,
      rehabilitation and community services, including the design of tailored
      instruments and referral pathways, delivered by two mental health professionals.
      SETTING AND PARTICIPANTS: Four adult acute and two rehabilitation wards (129
      beds), and the community recovery team (2038 cases) of the United Kingdom's
      largest Mental Health Trust. MEASUREMENTS: Audit of smoking information in
      patient notes; service uptake; quit attempts; smoking cessation and reduction;
      qualitative data on implementation barriers/facilitators. FINDINGS: A total of
      110 patients attended at least one support session: 53 inpatients (23% of
      inpatient smokers) and 57 community (of unknown number of community smokers, as
      recording of smoking status is not mandatory). Thirty-four of these (31%) made a
      quit attempt; 17 (15%) stopped smoking and 29 (26%) reduced cigarette consumption
      by up to 50% at the final contact. Barriers to service implementation related to:
      (i) trust policy, systems and procedures, (ii) staff knowledge and attitudes and
      (iii) illness-related factors. CONCLUSIONS: Despite the strong anti-smoking
      climate in the United Kingdom, including a law requiring smoke-free policies in
      mental health settings, establishing a smoking cessation treatment service for
      people with mental illness proved difficult, due to complex systemic barriers.
      However, there is clearly a demand, by patients, for such a service.

PMID- 23121357
TI  - Barriers and facilitators to a criminal justice tobacco control coordinator: an
      innovative approach to supporting smoking cessation among offenders.
AB  - AIMS: To examine the barriers and facilitators to effective operation of a
      regional tobacco control coordinator working within and across criminal justice
      and public health, whose goal was to raise tobacco control awareness and support
      the development of smoking cessation treatment for offenders. DESIGN: A
      reflexive, mixed-methods case study approach using in-depth interviews, project
      reports and observation of advisory board meetings. SETTING: The coordinator
      worked with prisons, probation and police custody, where there are high levels of
      social disadvantage and smoking. PARTICIPANTS: Interviews (n = 34) at different
      stages of project with the coordinator, project advisers and local stakeholders
      from criminal justice and public health. MEASUREMENTS: Analysis of facilitators
      and barriers and the coordinator role from different perspectives. FINDINGS:
      Readiness to develop cessation services was a critical predictor of different
      criminal justice settings' engagement with the coordinator role. The coordinator
      enhanced cessation service delivery in individual prisons where there was a
      requirement and infrastructure in place to provide such services. In police
      custody, where there was no central guidance or pre-existing requirements,
      efforts to establish smoking cessation on the local agenda proved ineffective. In
      probation settings, the coordinator documented examples of good practice and
      supported brief intervention training. Variability in willingness to engage
      limited the project's ability to create joined-up working across criminal justice
      settings. CONCLUSIONS: In the English criminal justice system, the prison service
      appears to provide a favourable context for development of smoking cessation
      support and a means of accessing hard-to-reach groups. Other criminal justice
      settings, most specifically police custody, appear less responsive to such
      activity. A coordinator role can improve smoking cessation support in the prison
      setting, and develop local improvements in tobacco control interventions in other
      settings such as probation, but as configured here, does not have the capacity to
      effect change across the criminal justice system.

PMID- 23121358
TI  - Using text messaging to prevent relapse to smoking: intervention development,
      practicability and client reactions.
AB  - AIMS: The NHS Stop Smoking Service (NHS-SSS) helps approximately half its clients
      to quit for 4 weeks. However, most initially successful quitters relapse within 6
      months. Short message service (SMS) texting has been shown to facilitate stopping
      smoking. We describe the development, implementation and subsequent evaluation,
      in terms of practicability and client response, of an SMS text-based relapse
      prevention intervention (RPI) delivered within routine community and specialist
      National Health Service (NHS) Stop Smoking Service (SSS) provision in four
      Primary Care Trusts. DESIGN: Text messages aimed at motivation to remain
      abstinent, preventing careless lapses and continuing the full course of medicine
      for smoking cessation were developed and sent weekly to clients' mobile phones
      for 12 weeks and fortnightly for 6 months. They were asked to respond to some of
      the texts and contact the NHS SSS if they lapsed. They were also offered free
      nicotine mini lozenges to be sent via the mail on three occasions. SETTING: NHS
      SSS. PARTICIPANTS: 202 clients who had been abstinent for 4 weeks. MEASUREMENTS:
      Feasibility of introducing RPI into routine care; response to interactive
      messages and requests for the medication; rating of the helpfulness of RPI; self
      reported and carbon monoxide (CO)-validated smoking status for up to 26 weeks.
      FINDINGS: A text-based RPI was easy to implement within the NHS SSS provided by
      specialist advisers, but enrollment of clients from services provided by a
      network of pharmacists was difficult because client contact details were often
      lacking. Where records of the number of people invited to RPI were available, 94%
      of eligible participants enrolled. The RPI was well received by both SSS clients
      and staff, with 70% (n = 63) of clients who completed follow-up considering the
      intervention helpful. Eighty-five per cent (n = 172) of clients responded to at
      least one of the nine interactive text messages. Sixty-four clients (32% of the
      total, 47% of those we managed to contact) reported continuous abstinence at 6
      months. Eighteen (9%) clients who relapsed to smoking used the RPI to re-engage
      with the NHS SSS and 10 (5%) successfully re-established abstinence. CONCLUSIONS:
      In smokers attending National Health Service Stop Smoking Services who are
      abstinent 4 weeks after their quit date, a relapse prevention intervention based
      on SMS text messaging was well received, and can be implemented economically and
      rapidly. A controlled trial is needed to establish whether it has a significant
      impact on relapse.

PMID- 23121359
TI  - Smokeless tobacco cessation in South Asian communities: a multi-centre
      prospective cohort study.
AB  - AIM: To evaluate smokeless tobacco cessation in communities of South Asian
      origin. DESIGN: Multi-centre prospective cohort study. SETTING: Three tobacco
      cessation services offering specialist smokeless tobacco cessation outreach
      clinic support to South Asians (Bangladeshi, Indian and Pakistani) resident in
      England. PARTICIPANTS: A total of 239 South Asian participants seeking to stop
      smokeless tobacco use between November 2010 and December 2011. MEASUREMENTS:
      Socio-demographics, tobacco use and dependence, self-reported abstinence at 4
      weeks and satisfaction measures. FINDINGS: Participants' mean age was 45
      [standard deviation (SD) = 13] years, were predominantly female (76%), of
      Bangladeshi origin (74%), either home carers (53%) or not working (29%). Sixty
      three per cent were recruited from community locations, 21% through a clinical
      contact and 16% through friends and family. Mean daily number of smokeless
      tobacco intakes was 10 (SD = 7) and the mean dependence score was 4.5 (SD = 1.9).
      Sixty-three per cent of participants achieved continuous abstinence 4 weeks after
      quitting. Using nicotine replacement therapy (NRT) versus not using it [OR =
      3.47, 95% confidence interval (CI): 1.25, 9.62] and below median (<= 8) daily
      smokeless tobacco intakes (OR = 1.91, 95% CI: 1.07, 3.40) predicted successful
      abstinence. CONCLUSION: South Asian smokeless tobacco users resident in England
      accessing services to help them stop appear to have short-term success rates
      comparable with smokers attending stop-smoking services, with higher success
      rates being reported by those using nicotine replacement therapy.

PMID- 23121360
TI  - Implementation of routine biochemical validation and an 'opt out' referral
      pathway for smoking cessation in pregnancy.
AB  - AIMS: To introduce an 'opt out' referral pathway for smoking cessation in
      pregnancy and to compare different methods for identifying pregnant smokers in
      maternity care. DESIGN: Pilot study that analysed routine data from maternity and
      smoking cessation services with biochemical validation of smoking status.
      SETTING: Dudley and South Birmingham, England. PARTICIPANTS: A total of 3712
      women who entered the referral pathway-1498 in Dudley and 2214 in South
      Birmingham. MEASUREMENTS: Routine monitoring data on smoking at maternity
      booking, referral to smoking cessation services, number of women who set quit
      dates set and short-term (4-week) self-report smoking status. Comparison of self
      report, carbon monoxide (CO)-validated and urinary cotinine-validated smoking
      status for a subsample (n = 1492) of women at maternity booking. FINDINGS: In
      Dudley 27% of women who entered the opt out referral pathway were identified as
      smokers following CO testing. Of those referred to the smoking cessation
      services, 19% reported stopping smoking at 4-week follow-up. In South Birmingham
      17% were smokers at booking, with 5% of those referred recorded as non-smokers at
      4 weeks. The number of women quitting did not increase during the study when
      compared with the previous year, despite higher referral rates in both areas. An
      optimum cut-off CO measurement of 4 parts per million (p.p.m.) was identified for
      sensitivity and specificity. CONCLUSION: The introduction of an opt out referral
      pathway between maternity and stop smoking services resulted in more women being
      referred for support to quit but not higher numbers of quitters, suggesting that
      automatic referral may include women who are not motivated to stop and who may
      not engage with services. Routine carbon monoxide monitoring introduced as part
      of a referral pathway should involve a cut-off of 4 p.p.m. to identify smoking in
      pregnancy.

PMID- 23121361
TI  - Factors associated with HCV antiviral treatment uptake among participants of a
      community-based HCV programme for marginalized patients.
AB  - While the majority of cases of hepatitis C virus (HCV) in developed countries
      occur among illicit drug users, HCV antiviral treatment uptake is poor in this
      population. Several studies have shown that patients can successfully be treated
      for HCV in the context of methadone maintenance programmes, but little evidence
      exists evaluating HCV treatment models for substance users where methadone
      maintenance is not indicated. This retrospective cohort study involved 129
      persons participating in psycho-educational support groups and integrated,
      interprofessional, community-based health services focused on the treatment for
      HCV among marginalized populations with high rates of crack cocaine use and
      mental health comorbidities. We sought to identify the factors associated with
      antiviral treatment uptake. Group participation improved access to health care.
      While 19% had previously seen an HCV specialist prior to group initiation, 59%
      saw an HCV specialist during the group. Half of the participants were nonimmune
      to hepatitis A or B at baseline, and 80% of these patients received immunization
      through the programme. The programme treated 24 patients with pegylated
      interferon and ribavirin and achieved a sustained virologic response (SVR) rate
      of 91% for genotype 2 or 3 and 54% for genotype 1. Stable housing was
      independently associated with initiation of treatment, and there was a
      nonsignificant trend towards lower rates of treatment initiation among women. SVR
      rates for those who had used crack or injection drugs in the month prior to
      joining the programme did not differ significantly from those who had abstained.

PMID- 23121362
TI  - Distinct and overlapping genomic profiles and antiviral effects of Interferon
      lambda and -alpha on HCV-infected and noninfected hepatoma cells.
AB  - Recently, several SNPs in the region of the IL28B (IFN-lambda) gene have been
      associated with spontaneous clearance of hepatitis C virus (HCV) and enhanced
      cure rates for IFN-alfa-based therapies, suggesting a potential correlation
      between IFN-lambda and the ability to clear HCV. To understand the mechanism of
      IFN-lambda's as compared to IFN-alpha's antiviral activity, we performed a
      comprehensive analysis of their anti-HCV effects, whole genome transcriptome
      profiling with validation, and signalling of IFN-alpha and IFN-lambda using
      J6/JFH-1 and Huh7.5 cells in vitro. IFN-lambda and IFN-alpha exhibited comparable
      anti-HCV activity and gene expression profiles in Huh7.5 cells. While the
      majority of genes induced by IFN-alpha and IFN-lambda were similar, IFN-lambda
      exhibits profound, but delayed kinetics of IFN-stimulated genes (ISG) induction,
      while IFN-alpha induced more rapid induction of ISGs. Furthermore, the increased
      induction of ISG expression by IFN-lambda correlated with up-regulation of IFN
      lambda receptor (IL-28RA) expression and more prolonged activation of the Jak
      STAT signalling pathway. The findings from our comparative analysis of IFN-alpha
      and IFN-lambda in HCV-infected and noninfected cells support the clinical use of
      IFN-lambda as a potential alternative to IFN-alpha in the treatment of chronic
      hepatitis C.

PMID- 23121363
TI  - Tamoxifen alleviates hepatitis C virus-induced inhibition of both toll-like
      receptor 7 and JAK-STAT signalling pathways in PBMCs of infected Egyptian
      females.
AB  - Summary.  Hepatitis C virus (HCV) is a major health concern in Egypt being highly
      prevalent among Egyptians. The two genders experience different responses to HCV
      infection and show variations in response to interferon (IFN)-based therapy that
      may be attributed to sex hormones. We previously demonstrated the suppressive
      effect of 17beta-estradiol (E2) on the expression of the IFN-stimulated gene MxA
      in HCV-infected peripheral blood mononuclear cells (PBMCs). The selective
      oestrogen receptor (ER) modulator Tamoxifen has been shown to have an antiviral
      effect against HCV, but its effect on the host immune response is unknown. We
      investigated the effect of Tamoxifen on the IFN signalling pathways in PBMCs of
      HCV-infected Egyptian females. We pooled PBMCs and treated then with exogenous
      interferon alpha (IFNalpha) or the TLR7 ligand, Imiquimod, and quantified the
      relative expressions of MxA using RTqPCR. Studies were performed with and without
      Tamoxifen pretreatment. Pretreatment with Tamoxifen reversed the suppressive
      effect of E2 on the JAK-STAT pathway in IFNalpha-treated PBMCs as indicated by a
      significant increase in MxA expression (P = 0.05*). Tamoxifen pretreatment also
      significantly upregulated MxA expression in Imiquimod-treated PBMCs (P =
      0.0011**), an effect not ascribed to ER blocking nor to an upregulation in TLR7
      expression because Tamoxifen showed no potentiating effect on the expression of
      the receptor. In conclusion, our findings reveal that Tamoxifen has
      immunomodulatory effects whereby it enhances the host IFN signalling pathways
      during HCV infection.

PMID- 23121364
TI  - The conserved lysine 151 of HCV NS5B modulates viral genome replication and
      infectious virus production.
AB  - Hepatitis C virus (HCV) nonstructural protein 5B (NS5B) is an RNA-dependent RNA
      polymerase (RdRp) that is involved in genome replication and virus assembly. NS5B
      contains a distinct loop (loop Lambda2) at the beginning of the nucleoside
      triphosphate tunnel with a highly conserved lysine (K151). In this study, reverse
      genetic analysis revealed that substitution of Jc1 NS5B K151 for alanine (K151A)
      and aspartic acid (K151D) affected genome replication and infectious virus
      production. However, genome replication and virus production by Jc1 containing
      NS5B K151R remained unaltered. A major deletion in loop Lambda2 abolished RNA
      replication, suggesting a role for this structural domain in NS5B polymerase
      activity. In conclusion, this study demonstrated that the conserved K151
      modulates infectious virus production; and loop Lambda2 is essential for the
      polymerase activity of NS5B.

PMID- 23121365
TI  - IL28B genetic variation and hepatitis C virus-specific CD4(+)  T-cell responses
      in anti-HCV-positive blood donors.
AB  - Epidemiological, viral and host factors are associated with the outcome of
      hepatitis C virus (HCV) infection, and strong host immune responses against HCV
      favour viral clearance. Recently, genome-wide association studies have shown a
      strong correlation between single-nucleotide polymorphisms (SNPs) near the
      interleukin-28B (IL28B) gene and spontaneous or treatment-induced HCV clearance.
      We have investigated whether protective IL28B genetic variants are associated
      with HCV-specific T-cell responses among Spanish blood donors. The rs12979860
      IL28B haplotype was determined in 69 anti-HCV-positive blood donors (21 HCV RNA
      negative and 48 HCV RNA positive) and 30 seronegative donors. In all cases, HCV
      specific CD4(+) T-cell responses to HCV recombinant proteins (core, NS3 and NS3
      helicase) were assessed by ex vivo interferon-gamma ELISpot assay. The rs12979860
      CC genotype was highly overrepresented in donors with spontaneous HCV clearance
      when compared to those with chronic infection (76.2%vs 29.2%, P < 0.001; odds
      ratio, 7.77; 95% confidence interval, 2.4-25.3, P < 0.001). HCV-specific CD4(+) T
      cell responses were detected in 16 (76.2%) spontaneous resolvers especially
      towards nonstructural proteins, but with no correlation with IL28B genotype.
      Chronic individuals had a significantly lower overall T-cell response again
      irrespective of IL28B genotype. When spontaneous resolvers and chronic
      individuals were stratified according to their IL28B genotype, significantly
      stronger T-cell responses were only observed among those with non-CC haplotypes.
      Although the protective rs12979860 IL28B CC genotype is associated with
      spontaneous HCV clearance, stronger CD4(+) T-cell responses towards NS3 were only
      evident among those with non-CC haplotypes.

PMID- 23121366
TI  - T-cell responses to hepatitis B splice-generated protein of hepatitis B virus and
      inflammatory cytokines/chemokines in chronic hepatitis B patients. ANRS study: HB
      EP 02 HBSP-FIBRO.
AB  - A new hepatitis B virus (HBV) protein, hepatitis B splice-generated protein
      (HBSP), has been detected in liver biopsy specimens from patients with chronic
      active hepatitis. The aim of this study was to characterize the phenotype and
      functions of peripheral HBSP-specific T cells and to determine whether these T
      cell responses may be implicated in liver damage or viral control. Two groups of
      patients were studied: HBV-infected patients with chronic active hepatitis and
      HBV-infected patients who were inactive carriers of hepatitis B surface antigen.
      HBSP-specific T-cell responses were analysed ex vivo and after in vitro
      stimulation of peripheral blood mononuclear cells. Soluble cytokines and
      chemokines were analysed in sera and in cell culture supernatants. Few HBSP- or
      capsid-specific T-cell responses were detected in patients with chronic active
      hepatitis whereas frequency of HBV-specific T cells was significantly higher in
      inactive carrier patients. HBSP activated CD8+ and CD4+ T cells that recognized
      multiple epitopes and secreted inflammatory cytokines. The IL-12 level was
      significantly lower in sera from asymptomatic carrier patients compared to
      patients with chronic active hepatitis. IL-12 and IP-10 levels in the sera were
      significantly and independently correlated with both alanine amino transferase
      and HBV DNA levels. Our results show that the HBSP protein activates cellular
      immune responses in HBV-infected patients but has probably no prominent role in
      liver damage. The pattern of cytokines and chemokines in sera was linked to HBV
      viral load and was consistent with the level of inflammation during chronic
      hepatitis.

PMID- 23121323
TI  - Strategies for multivessel revascularization in patients with diabetes.
AB  - BACKGROUND: In some randomized trials comparing revascularization strategies for
      patients with diabetes, coronary-artery bypass grafting (CABG) has had a better
      outcome than percutaneous coronary intervention (PCI). We sought to discover
      whether aggressive medical therapy and the use of drug-eluting stents could alter
      the revascularization approach for patients with diabetes and multivessel
      coronary artery disease. METHODS: In this randomized trial, we assigned patients
      with diabetes and multivessel coronary artery disease to undergo either PCI with
      drug-eluting stents or CABG. The patients were followed for a minimum of 2 years
      (median among survivors, 3.8 years). All patients were prescribed currently
      recommended medical therapies for the control of low-density lipoprotein
      cholesterol, systolic blood pressure, and glycated hemoglobin. The primary
      outcome measure was a composite of death from any cause, nonfatal myocardial
      infarction, or nonfatal stroke. RESULTS: From 2005 through 2010, we enrolled 1900
      patients at 140 international centers. The patients' mean age was 63.1+/-9.1
      years, 29% were women, and 83% had three-vessel disease. The primary outcome
      occurred more frequently in the PCI group (P=0.005), with 5-year rates of 26.6%
      in the PCI group and 18.7% in the CABG group. The benefit of CABG was driven by
      differences in rates of both myocardial infarction (P<0.001) and death from any
      cause (P=0.049). Stroke was more frequent in the CABG group, with 5-year rates of
      2.4% in the PCI group and 5.2% in the CABG group (P=0.03). CONCLUSIONS: For
      patients with diabetes and advanced coronary artery disease, CABG was superior to
      PCI in that it significantly reduced rates of death and myocardial infarction,
      with a higher rate of stroke. (Funded by the National Heart, Lung, and Blood
      Institute and others; FREEDOM ClinicalTrials.gov number, NCT00086450.).

PMID- 23121367
TI  - Factors associated with access to antiviral treatment in a multicentre cross
      sectional study of patients with chronic hepatitis B in Italy.
AB  - A multicentre cross-sectional survey was performed to provide an accurate picture
      of patients with chronic hepatitis B (CHB) cared for by Italian Infectious
      Diseases Centers (IDCs). This analysis describes factors associated with access
      to the treatment of CHB in a country where barriers to treatment are not expected
      to exist because of comprehensive coverage under the National Health System
      (NHS). The study was performed in 74 IDCs. The analysis focused on 3305 patients
      with CHB of 3760 HBsAg-positive patients enrolled from March to September, 2008.
      To account for missing values, a Multiple Imputation method was used. Treatment
      was reported in 2091 (63.3%) patients. In the multivariate analysis, an increased
      chance of getting treatment was independently associated with 10 years increase
      of age at diagnosis (adjusted odds ratio [aOR] 1.2, 95% confidence interval [CI]
      1.1-1.3, P < 0.001), HBeAg positivity (aOR 1.8, 95% CI 1.1-2.8, P < 0.001),
      cirrhosis (aOR 3.6, 95% CI 2-6.3, P = 0.012), HDV (aOR 1.6, 95% CI 1.02-2.5, P =
      0.042) and HIV positivity (aOR 6.5, 95% CI 4-10.8, P < 0.001). Conversely, a
      decreased chance was associated with female gender (aOR 0.6, 95% CI 0.5-0.7, P <
      0.001), immigration (aOR 0.6, 95% CI 0.5-0.9, P = 0.009), alcohol consumption
      (aOR 0.7, 95% CI 0.5-0.98, P = 0.04) and HCV positivity (aOR 0.5, 95% CI 0.3-0.8,
      P = 0.005). Our study shows that Italian IDCs treat a high percentage of patients
      with CHB. Nevertheless, disparities exist which are not related to the severity
      of disease limiting access to antiviral therapy of CHB, even in a country with a
      universal healthcare system.

PMID- 23121368
TI  - Tolerability and efficacy of anti-HBV nucleos(t)ide analogues in HBV-DNA-positive
      cirrhotic patients with HBV/HCV dual infection.
AB  - We evaluated tolerability and virological and clinical impact of anti-Hepatitis B
      Virus (HBV) nucleos(t)ide analogues in cirrhotic patients with HBV/Hepatitis C
      Virus (HCV) coinfection. The virological and clinical course of 24 consecutive
      HBsAg/HBV-DNA/anti-HCV-positive patients with cirrhosis was compared with that of
      24 HBsAg/HBV-DNA-positive, anti-HCV-negative cirrhotic patients, pair-matched for
      age (+/-5 years), sex, HBeAg/anti-HBe status and Child-Pugh class. Patients in
      both groups were previously untreated with oral antiviral agents at enrollment
      and were treated for at least 24 months (range 24-54). At the 12th and 18th month
      of treatment, HBV-DNA was negative in 21 (87.5%) and 23 (95.8%) patients with
      hepatitis B and C and in 20 (83.3%) and 22 (91.6%) in patients with isolated HBV;
      all patients in both groups were HBV-DNA-negative at month 24 and at subsequent
      observations. Treatment was well tolerated by all patients in both groups. At the
      last observation (for co-infected patients, median 44 months and range 24-54; for
      mono-infected patients, median 40 months and range 24-54), a deterioration in
      Child class was observed in eight (47%) of 17 patients in patients with both HBV
      and HCV who were HCV-RNA-positive at baseline, but in none of seven HCV-RNA
      negative patients in the same group, and in one patient (4.2%) in the mono
      infected patients. Reactivation of HCV infection was relatively infrequent (12.5%
      of cases) and never associated with a clinical deterioration. Treatment with
      nucleotides in HBsAg/HBV-DNA/anti-HCV-positive patients with cirrhosis showed a
      favourable virological effect in all cases, but a favourable clinical result only
      in the HCV-RNA-negative at baseline.

PMID- 23121369
TI  - Spatial and temporal analysis of NADPH oxidase-generated hydrogen peroxide
      signals by novel fluorescent reporter proteins.
AB  - AIMS: Hydrogen peroxide (H2O2) is an emerging signaling molecule with diverse
      regulatory functions. Despite its significance, the spatial and temporal
      organization of H2O2 signals within cells is basically unknown. Our limited
      knowledge about H2O2 signals is largely due to the lack of appropriate techniques
      for measuring intracellular H2O2. The aim of the current study was to develop
      novel fluorescent reporter proteins for the measurement of intracellular H2O2.
      RESULTS: We developed two novel, fluorescence resonance energy transfer-based
      redox probes that undergo opposite emission ratio changes upon exposure to H2O2.
      We have successfully used these sensors to measure H2O2 production by NADPH
      oxidases (Nox). Moreover, we targeted these probes to specific cellular
      compartments or incorporated them into oxidase complexes to detect H2O2 at
      different, well-defined loci. INNOVATION: Studying Nox2- and dual oxidase 1
      (Duox1)-expressing cells, we provide the first analysis of how NADPH-oxidase
      generated H2O2 signals radiate within and between cells. CONCLUSION: Our results
      suggest that H2O2 produced by Noxs can induce redox changes in the intracellular
      milieu of Nox/Duox-expressing cells while simultaneously transmitting paracrine
      effects to neighboring cells.

PMID- 23121370
TI  - Nutrition and oxidative stress: a systematic review of human studies.
AB  - Oxidative stress (OS) - defined as the imbalance between free radical production
      and antioxidant defences - is a condition associated with chronic-degenerative
      disease, such as cancer, metabolic and disease cardiovascular diseases (CVDs).
      Several studies have shown that diet and some of its components could influence
      the intensity of OS damage. The aim of this review was to critically examine some
      pieces of evidence from observational and intervention study in human beings to
      assess whether diet and its components can really modify OS in vivo. Furthermore,
      we tried to find out the possible mechanism behind this association. We
      considered all studies in MEDLINE which fitted with the following criteria: (1)
      adult subjects who were healthy or affected by metabolic disease and CVDs; (2) no
      food supplements, pillows, powder but only common foods and beverages and (3) OS
      assessment with well-known and validated in vivo biomarkers.

PMID- 23121371
TI  - Involvement of the apelin receptor APJ in Fas-induced liver injury.
AB  - BACKGROUND: Apelin-APJ signalling is known to play important roles in heart
      physiology and pathology; however, its functions in liver physiology and
      pathology remain unclear. On the other hand, Fas is an important molecule in
      hepatitis and other liver disease that belongs to the death receptor family. The
      aim of this study was to assess the relationship between apelin-APJ signaling and
      Fas-mediated liver injury in mice. METHODS: APJ(-/-) mice and wild type (WT) mice
      were administered an intraperitoneal injection of an agonistic anti-Fas antibody
      (clone; Jo2), and sacrificed after 3 or 6 h to assess the liver histology. The
      expression levels of apelin and APJ, plasma levels of transaminases, activities
      of hepatic caspases and activations of stress-activated protein kinases were also
      analysed. RESULTS: Before the Jo2 injection, APJ was weakly expressed in the
      hepatocytes in spots; on the other hand, after the Jo2 injection, it had spread
      into whole hepatocytes. Moreover, the mRNA expression level of apelin and APJ in
      the liver increased after Jo2 injection. In the APJ(-/-) mice, the liver injuries
      and apoptotic changes were significantly inhibited as compared with those in the
      WT mice. Dramatic increase in JNK activation was observed in the WT mice after
      Jo2 injection, whereas such activation was completely absent in the APJ(-/-)
      mice. JNK inhibitor partially, but significantly suppressed Jo2-mediated liver
      injury in WT mice. CONCLUSION: Apelin-APJ signalling may promote Fas-induced
      liver injury at least partially via JNK activation, and may thus serve as a
      potential therapeutic target in cases of acute liver injury.

PMID- 23121372
TI  - The association of pre-operative physical fitness and physical activity with
      outcome after scheduled major abdominal surgery.
AB  - We studied whether reported physical activity and measurements of fitness (hand,
      leg and inspiration) were associated with postoperative in-hospital mortality,
      length of stay and discharge destination in 169 patients after major oncological
      abdominal surgery. In multivariate analysis, adequate activity level (OR 5.5, 95%
      CI 1.4-21.9) and inspiratory muscle endurance (OR 5.2, 95% CI 1.4-19.1) were
      independently associated with short-term mortality, whereas conventional factors,
      such as age and heart disease, were not. Adequate activity level (OR 6.7, 95% CI
      1.4-3.0) was also independently associated with discharge destination. The
      factors that were independently associated with a shorter length of hospital stay
      were as follows: absence of chronic obstructive pulmonary disease (HR 0.6, 95% CI
      0.3-1.1); adequate activity level (HR 0.6, 95% CI 0.4-0.8); and inspiratory
      muscle strength (HR 0.6, 95% CI 0.5-0.9). For all postoperative outcomes physical
      activity and fitness significantly improved the predictive value compared with
      known risk factors, such as age and comorbidities. We conclude that pre-operative
      questionnaires of physical activity and measurements of fitness contribute to the
      prediction of postoperative outcomes.

PMID- 23121373
TI  - Hypoglycaemia and accident risk in people with type 2 diabetes mellitus treated
      with non-insulin antidiabetes drugs.
AB  - AIMS: To assess associations between hypoglycaemia and risk of accidents
      resulting in hospital visits among people with type 2 diabetes receiving
      antidiabetes drugs without insulin. METHODS: People with type 2 diabetes who were
      not treated with insulin were identified from a US-based employer claims database
      (1998-2010). Following initiation of an antidiabetes drug, the occurrence of
      accidents resulting in hospital visits was compared between people with, and
      without, claims for hypoglycaemia using multivariable Cox proportional hazard
      models adjusted for demographics, comorbidities, prior treatments and prior
      medical service use. Additional analyses were stratified by age 65 years or
      older. RESULTS: A total of N = 5582 people with claims for hypoglycaemia and N =
      27,910 with no such claims were included. Accidents resulting in hospital visits
      occurred in 5.5 and 2.8% of people with, and without, hypoglycaemia,
      respectively. After adjusting for baseline characteristics, hypoglycaemia was
      associated with significantly increased hazards for any accident [hazard ratio
      (HR) 1.39, 95% CI 1.21-1.59, p < 0.001], accidental falls (HR 1.36, 95% CI 1.13
      1.65, p < 0.001) and motor vehicle accidents (HR 1.82, 95% CI 1.18-2.80, p =
      0.007). In age-stratified analyses, hypoglycaemia was associated with greater
      hazards of driving-related accidents in people younger than age 65 and falls in
      people aged 65 or older. CONCLUSIONS: In people with type 2 diabetes receiving
      antidiabetes drugs without insulin, hypoglycaemia was associated with a
      significantly higher risk of accidents resulting in hospital visits, including
      accidents related to driving and falls.

PMID- 23121375
TI  - Trials in kidney disease--time to EVOLVE.

PMID- 23121376
TI  - Aquaretic treatment in polycystic kidney disease.

PMID- 23121380
TI  - The development of a reliable amateur boxing performance analysis template.
AB  - The aim of this study was to devise a valid performance analysis system for the
      assessment of the movement characteristics associated with competitive amateur
      boxing and assess its reliability using analysts of varying experience of the
      sport and performance analysis. Key performance indicators to characterise the
      demands of an amateur contest (offensive, defensive and feinting) were developed
      and notated using a computerised notational analysis system. Data were subjected
      to intra- and inter-observer reliability assessment using median sign tests and
      calculating the proportion of agreement within predetermined limits of error. For
      all performance indicators, intra-observer reliability revealed non-significant
      differences between observations (P > 0.05) and high agreement was established
      (80-100%) regardless of whether exact or the reference value of +/-1 was applied.
      Inter-observer reliability was less impressive for both analysts (amateur boxer
      and experienced analyst), with the proportion of agreement ranging from 33-100%.
      Nonetheless, there was no systematic bias between observations for any indicator
      (P > 0.05), and the proportion of agreement within the reference range (+/-1) was
      100%. A reliable performance analysis template has been developed for the
      assessment of amateur boxing performance and is available for use by researchers,
      coaches and athletes to classify and quantify the movement characteristics of
      amateur boxing.

PMID- 23121379
TI  - Controlled oxidation of remote sp3 C-H bonds in artemisinin via P450 catalysts
      with fine-tuned regio- and stereoselectivity.
AB  - The selective oxyfunctionalization of isolated sp(3) C-H bonds in complex
      molecules represents a formidable challenge in organic chemistry. Here, we
      describe a rational, systematic strategy to expedite the development of P450
      oxidation catalysts with refined regio- and stereoselectivity for the
      hydroxylation of remote, unactivated C-H sites in a complex scaffold. Using
      artemisinin as model substrate, we demonstrate how a three-tier strategy
      involving first-sphere active site mutagenesis, high-throughput P450
      fingerprinting, and fingerprint-driven P450 reactivity predictions enabled the
      rapid evolution of three efficient biocatalysts for the selective hydroxylation
      of a primary and a secondary C-H site (with both S and R stereoselectivity) in a
      relevant yet previously inaccessible region of this complex natural product. The
      evolved P450 variants could be applied to provide direct access to the desired
      hydroxylated derivatives at preparative scales (0.4 g) and in high isolated
      yields (>90%), thereby enabling further elaboration of this molecule. As an
      example, enantiopure C7-fluorinated derivatives of the clinical antimalarial
      drugs artesunate and artemether, in which a major metabolically sensitive site is
      protected by means of a C-H to C-F substitution, were afforded via P450-mediated
      chemoenzymatic synthesis.

PMID- 23121381
TI  - In silico prediction of aqueous solubility using simple QSPR models: the
      importance of phenol and phenol-like moieties.
AB  - Recently the authors published a robust QSPR model of aqueous solubility which
      exploited the computationally derived molecular descriptor topographical polar
      surface area (TPSA) alongside experimentally determined melting point and logP.
      This model (the "TPSA model") is able to accurately predict to within +/- one log
      unit the aqueous solubility of 87% of the compounds in a chemically diverse data
      set of 1265 molecules. This is comparable to results achieved for established
      models of aqueous solubility e.g. ESOL (79%) and the General Solubility Equation
      (81%). Hierarchical clustering of this data set according to chemical similarity
      shows that a significant number of molecules with phenolic and/or phenol-like
      moieties are poorly predicted by these equations. Modification of the TPSA model
      to additionally incorporate a descriptor pertaining to a simple count of phenol
      and phenol-like moieties improves the predictive ability within +/- one log unit
      to 89% for the full data set (1265 compounds -8.48 < logS < 1.58) and 82% for a
      reduced data set (1160 compounds 6.00 < logS < 0.00) which excludes compounds at
      the sparsely populated extremities of the data range. This improvement can be
      rationalized as the additional descriptor in the model acting as a correction
      factor which acknowledges the effect of phenolic substituents on the electronic
      characteristics of aromatic molecules i.e. the generally positive contribution to
      aqueous solubility made by phenolic moieties.

PMID- 23121382
TI  - Suppression of the allogeneic response by the anti-allergy drug N-(3,4
      dimethoxycinnamonyl) anthranilic acid results from T-cell cycle arrest.
AB  - Previously we have shown that indoleamine 2,3-dioxygenase (IDO) and the
      tryptophan metabolite, 3-hydroxykynurenine (3HK) can prolong corneal allograft
      survival. IDO modulates the immune response by depletion of the essential amino
      acid tryptophan by breakdown to kynurenines, which themselves act directly on T
      lymphocytes. The tryptophan metabolite analogue N-(3,4-dimethoxycinnamonyl)
      anthranilic acid (DAA, 'Tranilast') shares the anthranilic acid core with 3HK.
      Systemic administration of DAA to mice receiving a fully MHC-mismatched allograft
      of cornea or skin resulted in significant delay in rejection (median survival of
      controls 12 days, 13 days for cornea and skin grafts, respectively, and of
      treated mice 24 days (P < 0.0001) and 17 days (P < 0.03), respectively). We
      provide evidence that DAA-induced suppression of the allogeneic response, in
      contrast to that induced by tryptophan metabolites, was a result of cell cycle
      arrest rather than T-cell death. Cell cycle arrest was mediated by up-regulation
      of the cell cycle-specific inhibitors p21 and p15, and associated with a
      significant reduction in interleukin-2 production, allowing us to characterize a
      novel mechanism for DAA-induced T-cell anergy. Currently licensed as an anti
      allergy drug, the oral bioavailability and safe therapeutic profile of DAA make
      it a candidate for the prevention of rejection of transplanted cornea and other
      tissues.

PMID- 23121384
TI  - Establishment of medium for laboratory cultivation and maintenance of
      Fredericella sultana for in vivo experiments with Tetracapsuloides bryosalmonae
      (Myxozoa).
AB  - The freshwater bryozoan Fredericella sultana (Blumenbach) is the most common
      invertebrate host of the myxozoan parasite Tetracapsuloides bryosalmonae, the
      causative agent of proliferative kidney disease in salmonid fish. Culture media
      play an important role in hatching of statoblasts and maintaining clean bryozoan
      colonies for Malacosporea research. We developed a novel culture medium, Bryozoan
      Medium C (BMC), for the cultivation and maintenance of F. sultana under
      laboratory conditions. Statoblasts of F. sultana were successfully hatched to
      produce transparent-walled, specific pathogen-free (SPF) colonies that were
      maintained >12 months in BMC at pH 6.65. Tetracapsuloides bryosalmonae was
      successfully transmitted from infected brown trout, Salmo trutta L., to newly
      hatched F. sultana colonies in BMC, then from the infected bryozoan to SPF brown
      trout. This study demonstrated the utility of BMC (pH 6.65) for hatching
      statoblasts, long-term cultivation of clean and transparent bryozoan colonies and
      maintenance of the Tetracapsuloides bryosalmonae life cycle in the laboratory for
      molecular genetic research and other studies such as host-parasiteinteraction.

PMID- 23121377
TI  - Tolvaptan in patients with autosomal dominant polycystic kidney disease.
AB  - BACKGROUND: The course of autosomal dominant polycystic kidney disease (ADPKD) is
      often associated with pain, hypertension, and kidney failure. Preclinical studies
      indicated that vasopressin V(2)-receptor antagonists inhibit cyst growth and slow
      the decline of kidney function. METHODS: In this phase 3, multicenter, double
      blind, placebo-controlled, 3-year trial, we randomly assigned 1445 patients, 18
      to 50 years of age, who had ADPKD with a total kidney volume of 750 ml or more
      and an estimated creatinine clearance of 60 ml per minute or more, in a 2:1 ratio
      to receive tolvaptan, a V(2)-receptor antagonist, at the highest of three twice
      daily dose regimens that the patient found tolerable, or placebo. The primary
      outcome was the annual rate of change in the total kidney volume. Sequential
      secondary end points included a composite of time to clinical progression
      (defined as worsening kidney function, kidney pain, hypertension, and
      albuminuria) and rate of kidney-function decline. RESULTS: Over a 3-year period,
      the increase in total kidney volume in the tolvaptan group was 2.8% per year (95%
      confidence interval [CI], 2.5 to 3.1), versus 5.5% per year in the placebo group
      (95% CI, 5.1 to 6.0; P<0.001). The composite end point favored tolvaptan over
      placebo (44 vs. 50 events per 100 follow-up-years, P=0.01), with lower rates of
      worsening kidney function (2 vs. 5 events per 100 person-years of follow-up,
      P<0.001) and kidney pain (5 vs. 7 events per 100 person-years of follow-up,
      P=0.007). Tolvaptan was associated with a slower decline in kidney function
      (reciprocal of the serum creatinine level, -2.61 [mg per milliliter](-1) per year
      vs. -3.81 [mg per milliliter](-1) per year; P<0.001). There were fewer ADPKD
      related adverse events in the tolvaptan group but more events related to
      aquaresis (excretion of electrolyte-free water) and hepatic adverse events
      unrelated to ADPKD, contributing to a higher discontinuation rate (23%, vs. 14%
      in the placebo group). CONCLUSIONS: Tolvaptan, as compared with placebo, slowed
      the increase in total kidney volume and the decline in kidney function over a 3
      year period in patients with ADPKD but was associated with a higher
      discontinuation rate, owing to adverse events. (Funded by Otsuka Pharmaceuticals
      and Otsuka Pharmaceutical Development and Commercialization; TEMPO 3:4
      ClinicalTrials.gov number, NCT00428948.).

PMID- 23121383
TI  - Dried blood spots for the enzymatic diagnosis of lysosomal storage diseases in
      dogs and cats.
AB  - BACKGROUND: In people, lysosomal storage diseases (LSD) can be diagnosed by
      assaying enzyme activities in dried blood spots (DBS). OBJECTIVE: The aim of this
      study was to evaluate the feasibility of using DBS samples from dogs and cats to
      measure lysosomal enzymatic activities and diagnose LSD. METHODS: Drops of fresh
      whole blood collected in EDTA from dogs and cats with known or suspected LSD and
      from clinically healthy dogs and cats were placed on neonatal screening cards,
      dried, and mailed to the Metabolic Laboratory, University Children's Hospital,
      Frankfurt, Germany. Activities of selected lysosomal enzymes were measured using
      fluorescent substrates in a 2-mm diameter disk (~2.6 MUL blood) punched from the
      DBS. Results were expressed as nmol substrate hydrolyzed per mL of blood per
      minute or hour. RESULTS: Reference values were established for several lysosomal
      enzyme activities in DBS from dogs and cats; for most enzymes, activities were
      higher than those published for human samples. Activities of beta-glucuronidase,
      N-acetylglucosamine-4-sulfatase (arylsulfatase B), alpha-mannosidase, alpha
      galactosidase, alpha-fucosidase, and hexosaminidase A were measureable in DBS
      from healthy cats and dogs; alpha-iduronidase activity was measureable only in
      cats. In samples from animals with LSD, markedly reduced activity of a specific
      enzyme was found. In contrast, in samples from cats affected with mucolipidosis
      II, activities of lysosomal enzymes were markedly increased. CONCLUSIONS:
      Measurement of lysosomal enzyme activities in DBS provides an inexpensive,
      simple, and convenient method to screen animals for suspected LSD and requires
      only a small sample volume. For diseases in which the relevant enzyme activity
      can be measured in DBS, a specific diagnosis can be made.

PMID- 23121385
TI  - Ultrasound-enhanced drug delivery for cancer.
AB  - INTRODUCTION: Ultrasound, which has traditionally been used as a diagnostic tool,
      is increasingly being used in non-invasive therapy and drug delivery. AREAS
      COVERED: Of particular interest to this review is the rapidly accumulating
      evidence that ultrasound may have a key role to play both in improving the
      targeting and the efficacy of drug delivery for cancer. Currently available
      ultrasound-triggerable vehicles are first described, with particular reference to
      the ultrasonic mechanism that can activate release and the suitability of the
      size range of the vehicle used for drug delivery. Further mechanical and thermal
      effects of ultrasound that can enhance extravasation and drug distribution
      following release are then critically reviewed. EXPERT OPINION: Acoustic
      cavitation is found to play a potentially key role both in achieving targeted
      drug release and enhanced extravasation at modest pressure amplitudes and
      acoustic energies, whilst simultaneously enabling real-time monitoring of the
      drug delivery process. The next challenge in ultrasound-enhanced drug delivery
      will thus be to develop a new generation of drug-carrying nanoparticles which are
      of the right size range for delivery to tumours, yet still capable of achieving
      initiation of cavitation activity and drug release at modest acoustic pressures
      and energies that have no safety implications for the patient.

PMID- 23121374
TI  - Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis.
AB  - BACKGROUND: Disorders of mineral metabolism, including secondary
      hyperparathyroidism, are thought to contribute to extraskeletal (including
      vascular) calcification among patients with chronic kidney disease. It has been
      hypothesized that treatment with the calcimimetic agent cinacalcet might reduce
      the risk of death or nonfatal cardiovascular events in such patients. METHODS: In
      this clinical trial, we randomly assigned 3883 patients with moderate-to-severe
      secondary hyperparathyroidism (median level of intact parathyroid hormone, 693 pg
      per milliliter [10th to 90th percentile, 363 to 1694]) who were undergoing
      hemodialysis to receive either cinacalcet or placebo. All patients were eligible
      to receive conventional therapy, including phosphate binders, vitamin D sterols,
      or both. The patients were followed for up to 64 months. The primary composite
      end point was the time until death, myocardial infarction, hospitalization for
      unstable angina, heart failure, or a peripheral vascular event. The primary
      analysis was performed on the basis of the intention-to-treat principle. RESULTS:
      The median duration of study-drug exposure was 21.2 months in the cinacalcet
      group, versus 17.5 months in the placebo group. The primary composite end point
      was reached in 938 of 1948 patients (48.2%) in the cinacalcet group and 952 of
      1935 patients (49.2%) in the placebo group (relative hazard in the cinacalcet
      group vs. the placebo group, 0.93; 95% confidence interval, 0.85 to 1.02;
      P=0.11). Hypocalcemia and gastrointestinal adverse events were significantly more
      frequent in patients receiving cinacalcet. CONCLUSIONS: In an unadjusted
      intention-to-treat analysis, cinacalcet did not significantly reduce the risk of
      death or major cardiovascular events in patients with moderate-to-severe
      secondary hyperparathyroidism who were undergoing dialysis. (Funded by Amgen;
      EVOLVE ClinicalTrials.gov number, NCT00345839.).

PMID- 23121387
TI  - In vitro fermentation of grape seed flavan-3-ol fractions by human faecal
      microbiota: changes in microbial groups and phenolic metabolites.
AB  - With the aim of investigating the potential of flavan-3-ols to influence the
      growth of intestinal bacterial groups, we have carried out the in vitro
      fermentation, with human faecal microbiota, of two purified fractions from grape
      seed extract (GSE): GSE-M (70% monomers and 28% procyanidins) and GSE-O (21%
      monomers and 78% procyanidins). Samples were collected at 0, 5, 10, 24, 30 and 48
      h of fermentation for bacterial enumeration by fluorescent in situ hybridization
      and for analysis of phenolic metabolites. Both GSE-M and GSE-O fractions promoted
      growth of Lactobacillus/Enterococcus and decrease in the Clostridium histolyticum
      group during fermentation, although the effects were only statistically
      significant with GSE-M for Lactobacillus/Enterococcus (at 5 and 10 h of
      fermentation) and GSE-O for C. histolyticum (at 10 h of fermentation). Main
      changes in polyphenol catabolism also occurred during the first 10 h of
      fermentation; however, no significant correlation coefficients (P > 0.05) were
      found between changes in microbial populations and precursor flavan-3-ols or
      microbial metabolites. Together, these data suggest that the flavan-3-ol profile
      of a particular food source could affect the microbiota composition and its
      catabolic activity, inducing changes that could in turn affect the
      bioavailability and potential bioactivity of these compounds.

PMID- 23121388
TI  - Tackling child health inequalities due to deprivation: using health equity audit
      to improve and monitor access to a community paediatric service.
AB  - BACKGROUND: Deprived children constitute a large population with high levels of
      ill health, and difficulty with access to healthcare contributes to their poor
      health outcomes. There is debate on how best to engage deprived families and the
      literature on differential access to paediatric care based on deprivation is
      limited. AIMS: To demonstrate that community paediatrics can contribute to
      reduction of health inequalities by providing services that are accessible to and
      preferentially used by children whose health is likely to be affected by
      deprivation. To provide a template for others to improve and monitor equity in
      their services. METHOD: Long-term service reconfiguration and health equity
      audit. We used routinely collected activity data and the Indices of Multiple
      Deprivation to construct equity profiles of the children using our service, and
      compared these with the profile of the population aged 0-16 years in the
      geographical area covered by the service. RESULTS: The new patient contact rate
      for the most deprived children in the population was more than three times that
      of the least deprived [odds ratio (OR) 3.29, 95% confidence interval (CI) 2.76
      3.93]. Deprived children were more than twice as likely to require multi-agency
      meetings as part of their medical care (OR 2.28, 95% CI 1.94-2.69). Seventy per
      cent (3693/5312) of our total contacts were with children in the two most
      deprived quintiles. There was a marked socio-economic gradient in all types of
      contact. CONCLUSIONS: The model of care used by our community paediatric service
      successfully engages deprived families, thereby reducing health inequalities due
      to poor access. Key features are multi-agency working, removing barriers to
      access, raising staff awareness and use of health equity audit. Our findings
      provide support for tackling health inequalities via health services that are
      available to all, but capable of responding proportionately according to level of
      need, a model recently described as proportionate universalism.

PMID- 23121389
TI  - The future of higher education.

PMID- 23121393
TI  - Rapid, microwave-assisted perdeuteration of polycyclic aromatic hydrocarbons.
AB  - A simple and convenient method for the perdeuteration of polycyclic aromatic
      hydrocarbons that does not require strong acid has been developed. Using
      commercially available reagents, the one-step procedure provides a new route to
      perdeuterated derivatives of both common and exotic polycyclic aromatic
      hydrocarbons. Microwave irradiation of the hydrocarbons in a solution of
      dimethylformamide-d7 containing potassium tert-butoxide affords rapid and
      essentially complete H/D exchange. For example, corannulene is converted to
      corannulene-d10 with >98% deuterium incorporation in just 1 h of microwave
      irradiation in a solution of t-BuOK/DMF-d7.

PMID- 23121392
TI  - Human umbilical cord mesenchymal stem cells as vehicles of CD20-specific TRAIL
      fusion protein delivery: a double-target therapy against non-Hodgkin's lymphoma.
AB  - Mesenchymal stem cells (MSCs) are an attractive candidate for cell-based therapy.
      We have designed a promising double-target therapeutic system for non-Hodgkin's
      lymphoma (NHL) therapy. The system is based on MSC homing capacity and scFvCD20
      antigen-restriction to NHL. In this system, a novel secreted fusion protein
      scFvCD20-sTRAIL, which contains a CD20-specific single chain Fv antibody fragment
      (scFv) and a soluble tumor necrosis factor related apoptosis-inducing ligand
      (sTRAIL, aa residues 114-281) with an isoleucine zipper (ISZ) added to the N
      terminal (ISZ-sTRAIL), was expressed in human umbilical cord derived mesenchymal
      stem cells (HUMSCs). When compared with ISZ-sTRAIL protein, the scFvCD20-sTRAIL
      fusion protein demonstrated a potent inhibition of cell proliferation in CD20
      positive BJAB cells, moderate inhibition in Raji cells, weak inhibition in CD20
      negative Jurkat cells, and no effect on normal human peripheral blood mononuclear
      cells (PBMCs). The scFvCD20-sTRAIL fusion protein also caused significant
      increase of cellular apoptosis through both extrinsic and intrinsic apoptosis
      signaling pathways. Using a NOD/SCID mouse subcutaneous BJAB lymphoma xenograft
      model, the tropism of the firefly luciferase (fLuc) labeled MSC was monitored by
      bioluminescent imaging (BLI) for fLuc activity. Our study indicated that HUMSCs
      selectively migrated to the tumor site after 24 h of intravenous injection and
      mice injected with the MSC.scFvCD20-sTRAIL significantly inhibited the tumor
      growth when compared with those treated with MSC.ISZ-sTRAIL. The treatment was
      tolerated well in mice, as no obvious toxicities were observed. Our study has
      suggested that scFvCD20-sTRAIL secreting HUMSCs is a novel and efficient
      therapeutic approach for the treatment of non-Hodgkin's lymphoma.

PMID- 23121386
TI  - Can neuropeptides treat obesity? A review of neuropeptides and their potential
      role in the treatment of obesity.
AB  - Obesity is a major worldwide public health issue. The physiological systems that
      regulate body weight are thus of great interest as targets for anti-obesity
      agents. Peptidergic systems are critical to the regulation of energy homeostasis
      by key regions in the hypothalamus and brainstem. A number of neuropeptide
      systems have therefore been investigated as potential treatments for obesity.
      Blocking orexigenic peptide signals such as neuropeptide Y, melanin-concentrating
      hormone, orexins, relaxin-3 and galanin-like peptide or stimulating anorectic
      signalling pathways used by peptides such as the melanocortins, ciliary
      neurotrophic factor and brain-derived neurotrophic factor, are approaches that
      have shown some promise, but which have also highlighted possible concerns.
      Manipulation of central peptidergic systems poses a number of therapeutic
      problems, including brain access and side effects. Given that the homeostatic
      defence of body weight may limit the effectiveness of any single-target therapy
      developed, a combination therapy approach may offer the best hope for the
      effective prevention and treatment of obesity. LINKED ARTICLES: This article is
      part of a themed section on Neuropeptides. To view the other articles in this
      section visit http://dx.doi.org/10.1111/bph.2013.170.issue-7.

PMID- 23121394
TI  - Male swimmers cross the English Channel faster than female swimmers.
AB  - We examined the gender difference in performance of open-water ultra-swimmers
      crossing the English Channel between 1875 and 2011. A total of 1606 swimmers
      (1120 males and 486 females) crossed the English Channel within a mean time of
      809.6 +/- 175.6 min. The overall female swim time of 796.3 +/- 188.7 min was not
      different compared with the overall male swim time of 815.4 +/- 169.4 min (P >
      0.05). The fastest male swim time ever of 417 min was 6.7% faster than the
      fastest female swim time ever with 445 min. The gender difference in performance
      of the top three times ever was 8.9 +/- 2.3%. Over the last 36 years, the
      performance of the annual top three swimmers showed no changes for both females
      and males. The top three males (564.3 +/- 63.8 min) were significantly faster
      than the top three females (602.1 +/- 58.7 min; P < 0.01). The gender difference
      remained unchanged at 12.5 +/- 9.6% over the years. To summarize, the top three
      male swimmers in the English Channel were ~12% faster than the females in the
      last 36 years. It seems unlikely that female open-water ultra-swimmers will
      overtop males in the near future in the English Channel.

PMID- 23121395
TI  - Rapid field identification of subjects involved in firearm-related crimes based
      on electroanalysis coupled with advanced chemometric data treatment.
AB  - We demonstrate a novel system for the detection and discrimination of varying
      levels of exposure to gunshot residue from subjects in various control scenarios.
      Our aim is to address the key challenge of minimizing the false positive
      identification of individuals suspected of discharging a firearm. The chemometric
      treatment of voltammetric data from different controls using Canonical Variate
      Analysis (CVA) provides several distinct clusters for each scenario examined.
      Multiple samples were taken from subjects in controlled tests such as secondary
      contact with gunshot residue (GSR), loading a firearm, and postdischarge of a
      firearm. These controls were examined at both bare carbon and gold-modified
      screen-printed electrodes using different sampling methods: the 'swipe' method
      with integrated sampling and electroanalysis and a more traditional acid-assisted
      q-tip swabbing method. The electroanalytical fingerprint of each sample was
      examined using square-wave voltammetry; the resulting data were preprocessed with
      Fast Fourier Transform (FFT), followed by CVA treatment. High levels of
      discrimination were thus achieved in each case over 3 classes of samples
      (reflecting different levels of involvement), achieving maximum accuracy,
      sensitivity, and specificity values of 100% employing the leave-one-out
      validation method. Further validation with the 'jack-knife' technique was
      performed, and the resulting values were in good agreement with the former
      method. Additionally, samples from subjects in daily contact with relevant
      metallic constituents were analyzed to assess possible false positives. This
      system may serve as a potential method for a portable, field-deployable system
      aimed at rapidly identifying a subject who has loaded or discharged a firearm to
      verify involvement in a crime, hence providing law enforcement personnel with an
      invaluable forensic tool in the field.

PMID- 23121396
TI  - Violence in the nursing workplace - a descriptive correlational study in a public
      hospital.
AB  - AIMS AND OBJECTIVES: To explore the prevalence, types and sources of violence in
      the nursing workplace and to assess the factors related to violence. BACKGROUND:
      Workplace violence in nursing is not a new phenomenon; in recent years, much more
      attention has been paid to the issue in Taiwan. Few studies, however, have
      investigated the overall distribution of violence and the reasons for not
      reporting these incidents in nursing workplaces. DESIGN: This descriptive,
      correlational study used structured questionnaires to collecting information
      about workplace violence experienced by nurses over the last year. METHODS:
      Nurses (n = 880) working in a public hospital in southern Taiwan were invited to
      complete the questionnaires, with a response rate of 89.9%. RESULTS: Nurses
      working in outpatient units and emergency rooms experienced more frequent
      violence than those on surgical wards and intensive care units. CONCLUSION: These
      findings provide evidence of workplace violence in hospitals and may aid hospital
      and nursing administration to reduce and control violence. RELEVANCE TO NURSING
      PRACTICE: These results provide evidence in relation to the importance of
      effective communication training to nurses and will assist hospital
      administrations in establishing higher-quality, healthy workplace environments.

PMID- 23121397
TI  - The factor H binding protein of Neisseria meningitidis interacts with
      xenosiderophores in vitro.
AB  - The factor H binding protein (fHbp) is a key virulence factor of Neisseria
      meningitidis that confers to the bacterium the ability to resist killing by human
      serum. The determination of its three-dimensional structure revealed that the
      carboxyl terminus of the protein folds into an eight-stranded beta barrel. The
      structural similarity of this part of the protein to lipocalins provided the
      rationale for exploring the ability of fHbp to bind siderophores. We found that
      fHbp was able to bind in vitro siderophores belonging to the cathecolate family
      and mapped the interaction site by nuclear magnetic resonance. Our results
      indicated that the enterobactin binding site was distinct from the site involved
      in binding to human factor H and stimulates new hypotheses about possible
      multiple activities of fHbp.

PMID- 23121398
TI  - The biology of recent thymic emigrants.
AB  - The generation of the TCRalphabeta lineage of T cells occurs in the thymus
      through a series of orchestrated developmental events that result in a carefully
      selected population of CD4 or CD8 lineage-committed TCR(+) thymocytes capable of
      recognizing foreign antigen in the context of self MHC. T cells first exit the
      thymus in a phenotypically and functionally immature state and require an
      approximately 3-week period of post-thymic maturation before transitioning into
      the mature T cell compartment. A greater understanding of recent thymic emigrant
      biology has come with the development of methods to exclusively identify and
      isolate this population for further characterization. I now review current
      knowledge about the phenotype and function of this key but understudied
      population of peripheral T cells.

PMID- 23121399
TI  - Conjugate vaccine introduction in the African meningitis belt: meeting
      surveillance objectives.
AB  - The epidemiology of bacterial meningitis will change with introduction of
      meningococcal and pneumococcal conjugate vaccines in the African meningitis belt.
      The principal objectives of surveillance are to evaluate the impact of
      vaccination, to detect and investigate epidemics and provide material for
      research. The capacity of existing surveillance activities in the meningitis belt
      to meet these objectives varies due to infrastructural and financial constraints.
      Impact assessment of conjugate vaccine against meningococcal serogroup A will be
      limited to comparing incidence trends from a few surveillance sites with data
      obtained before vaccine introduction and to comparing trends in the incidence of
      suspected cases or localised epidemics in most other settings. The timeliness of
      detection of epidemics and identification of epidemic meningococcal serogroups
      could be improved in most countries by analysing suspected case data in health
      centre level resolution and by investigating outbreaks with mobile teams. For
      research and impact assessment of pneumococcal conjugate vaccines, several
      surveillance sites covering at least 0.5 million inhabitants should be maintained
      which undertake exhaustive case finding and systematic laboratory confirmation of
      meningitis and pneumonia. Molecular diagnostics will facilitate surveillance in
      remote areas, but the available techniques should be evaluated for diagnostic
      performance in the field and long-term sustainability.

PMID- 23121400
TI  - A review of enhanced recovery for thoracic anaesthesia and surgery.
AB  - During the past decade, there has been a dramatic increase in the number of
      thoracic surgical procedures carried out in the UK. The current financial climate
      dictates that more efficient use of resources is necessary to meet escalating
      demands on healthcare. One potential means to achieve this is through the
      introduction of enhanced recovery protocols, designed to produce productivity
      savings by driving reduction in length of stay. These have been promoted by
      government bodies in a number of surgical specialties, including colorectal,
      gynaecological and orthopaedic surgery. This review focuses on aspects of peri
      operative care that might be incorporated into such a programme for thoracic
      anaesthesia, for which an enhanced recovery programme has not yet been introduced
      in the UK, and a review of the literature specific to this area of practice has
      not been published before. We performed a comprehensive search for published work
      relating to the peri-operative management and optimisation of patients undergoing
      thoracic surgery, and divided these into appropriate areas of practice. We have
      reviewed the specific interventions that may be included in an enhanced recovery
      programme, including: pre-optimisation; minimising fasting time; thrombo-embolic
      prophylaxis; choice of anaesthetic and analgesic technique and surgical approach;
      postoperative rehabilitation; and chest drain management. Using the currently
      available evidence, the design and implementation of an enhanced recovery
      programme based on this review in selected patients as a package of care may
      reduce morbidity and length of hospital stay, thus maximising utilisation of
      available resources.

PMID- 23121401
TI  - Liver involvement in Turner syndrome.
AB  - Liver test abnormalities are frequent in adult patients with Turner syndrome,
      corresponding to various pathophysiological mechanisms. Steatosis, steatofibrosis
      and steatohepatitis are the most frequently reported lesions, caused by metabolic
      disorders, which are commonly related to overweight. Marked architectural
      changes, including nodular regenerative hyperplasia, multiple focal nodular
      hyperplasia and cirrhosis, found in some patients, are associated with a risk of
      severe liver-related complications. Architectural changes are often observed and
      are associated with vascular disorders caused by congenitally abnormal vessels.
      Finally, small bile duct alterations resembling sclerosing cholangitis occur in
      several patients. Oestrogen replacement therapy does not cause liver toxicity in
      patients with Turner syndrome and is not contraindicated in case of elevated
      liver enzymes. Moreover, in recent studies, oestrogen therapy was reported to
      improve liver function tests. Because of the wide spectrum of potential liver
      injuries that may occur in Turner syndrome patients, a regular screening of liver
      enzymes is recommended for early detection and treatment.

PMID- 23121402
TI  - An indole derivative protects against acetaminophen-induced liver injury by
      directly binding to N-acetyl-p-benzoquinone imine in mice.
AB  - AIMS: Acetaminophen (APAP)-induced liver injury is mainly due to the excessive
      formation of reactive oxygen species (ROS) and reactive nitrogen species (RNS)
      through the formation of a reactive intermediate, N-acetyl-p-benzoquinone imine
      (NAPQI), in both humans and rodents. Here, we show that the indole-derived
      synthetic compound has a protective effect against APAP-induced liver injury in
      C57Bl/6 mice model. RESULTS: NecroX-7 decreased tert-butylhydroperoxide (t-BHP)-
      and APAP-induced cell death and ROS/RNS formation in HepG2 human hepatocarcinoma
      and primary mouse hepatocytes. In mice, NecroX-7 decreased APAP-induced
      phosphorylation of c-Jun N-terminal kinase (JNK) and 3-nitrotyrosine (3-NT)
      formation, and also protected mice from APAP-induced liver injury and lethality
      by binding directly to NAPQI. The binding of NecroX-7 to NAPQI did not require
      any of cofactors or proteins. NecroX-7 could only scavenge NAPQI when
      hepatocellular GSH levels were very low. INNOVATION: NecroX-7 is an indole
      derived potent antioxidant molecule, which can be bound to some types of radicals
      and especially NAPQI. It is well known that the NAPQI is a major intermediate of
      APAP, which causes necrosis of hepatocytes in rodents and humans. Thus, blocking
      NAPQI formation or eliminating NAPQI are novel strategies for the treatment or
      prevention of APAP-induced liver injury instead of GSH replenishment. CONCLUSION:
      Our data suggest that the indole-derivative, NecroX-7, directly binds to NAPQI
      when hepatic GSH levels are very low and the NAPQI-NecroX-7 complex is secreted
      to the blood from the liver. NecroX-7 shows more preventive and similar
      therapeutic effects against APAP-induced liver injury when compared to the effect
      of N-acetylcysteine in C57Bl/6 mice.

PMID- 23121378
TI  - Cardiorenal end points in a trial of aliskiren for type 2 diabetes.
AB  - BACKGROUND: This study was undertaken to determine whether use of the direct
      renin inhibitor aliskiren would reduce cardiovascular and renal events in
      patients with type 2 diabetes and chronic kidney disease, cardiovascular disease,
      or both. METHODS: In a double-blind fashion, we randomly assigned 8561 patients
      to aliskiren (300 mg daily) or placebo as an adjunct to an angiotensin-converting
      enzyme inhibitor or an angiotensin-receptor blocker. The primary end point was a
      composite of the time to cardiovascular death or a first occurrence of cardiac
      arrest with resuscitation; nonfatal myocardial infarction; nonfatal stroke;
      unplanned hospitalization for heart failure; end-stage renal disease, death
      attributable to kidney failure, or the need for renal-replacement therapy with no
      dialysis or transplantation available or initiated; or doubling of the baseline
      serum creatinine level. RESULTS: The trial was stopped prematurely after the
      second interim efficacy analysis. After a median follow-up of 32.9 months, the
      primary end point had occurred in 783 patients (18.3%) assigned to aliskiren as
      compared with 732 (17.1%) assigned to placebo (hazard ratio, 1.08; 95% confidence
      interval [CI], 0.98 to 1.20; P=0.12). Effects on secondary renal end points were
      similar. Systolic and diastolic blood pressures were lower with aliskiren
      (between-group differences, 1.3 and 0.6 mm Hg, respectively) and the mean
      reduction in the urinary albumin-to-creatinine ratio was greater (between-group
      difference, 14 percentage points; 95% CI, 11 to 17). The proportion of patients
      with hyperkalemia (serum potassium level, >=6 mmol per liter) was significantly
      higher in the aliskiren group than in the placebo group (11.2% vs. 7.2%), as was
      the proportion with reported hypotension (12.1% vs. 8.3%) (P<0.001 for both
      comparisons). CONCLUSIONS: The addition of aliskiren to standard therapy with
      renin-angiotensin system blockade in patients with type 2 diabetes who are at
      high risk for cardiovascular and renal events is not supported by these data and
      may even be harmful. (Funded by Novartis; ALTITUDE ClinicalTrials.gov number,
      NCT00549757.).

PMID- 23121404
TI  - Aspirin for dual prevention of venous and arterial thrombosis.

PMID- 23121405
TI  - Responses during exhaustive exercise at critical power determined from the 3-min
      all-out test.
AB  - The purpose of the present study was to examine oxygen consumption rate
      ([Vdot][Formula: see text]), heart rate (HR), and ratings of perceived exertion
      (RPE) responses, as well as time to exhaustion (Tlim) values during continuous
      rides at critical power (CP) determined from the 3-min all-out test. Eighteen
      participants (mean +/- s: 23.6 +/- 3.5 years; 72.7 +/- 18.2 kg) performed an
      incremental cycle ergometer test to exhaustion to determine peak oxygen
      consumption rate ([Vdot][Formula: see text] peak) and HR peak. Critical power was
      determined from the 3-min all-out test. Metabolic responses ([Vdot][Formula: see
      text] and heart rate), RPE, and Tlim were recorded during continuous rides to
      exhaustion at CP. Linear regression and t-tests were used to compare
      [Vdot][Formula: see text], heart rate, and RPE responses during the continuous
      rides to exhaustion. The Tlim at CP was 12.5 +/- 6.5 min. There were significant
      increases in [Vdot][Formula: see text], HR, and RPE during the continuous rides
      at CP and 15 of the 18 participants reached [Vdot][Formula: see text] peak at
      exhaustion. Therefore, the [Vdot][Formula: see text], heart rate, and RPE
      responses, as well as the Tlim values in the present study suggested that CP
      determined from the 3-min all-out test overestimated the "true" CP and was within
      the severe exercise intensity domain.

PMID- 23121406
TI  - Chemically modified tetracyclines as inhibitors of MMP-2 matrix
      metalloproteinase: a molecular and structural study.
AB  - The present study focuses on the direct interaction of chemically modified
      tetracyclines (CMTs) with the active site of the matrix metalloproteinase 2 (MMP
      2). Molecular docking, molecular dynamics (MD) simulations, and free energy
      calculations were accomplished for seven CMT derivatives. New sets of parameters
      are proposed for structural and catalytic zinc atoms in order to study MMPs and
      their complexes by means of the AMBER force field. Our computational results show
      that six CMTs studied bind to the catalytic zinc of the MMP-2 enzyme at the O11
      O12 site as proposed experimentally. The exception was the CMT-3 analogue that is
      found embedding within the active site, enhancing the van der Waals and
      hydrophobic contacts with the hydrophobic S1' pocket in the MMP-2 enzyme. The
      binding energy calculated in solution predicts the CMT-3 complexes as the most
      favorable, followed by the CMT-7 and CMT-8 analogues, respectively, which is in
      line with experimental findings. This work is the first step toward understanding
      the mechanism of CMTs as MMP inhibitors at a molecular level.

PMID- 23121403
TI  - Low-dose aspirin for preventing recurrent venous thromboembolism.
AB  - BACKGROUND: Patients who have had a first episode of unprovoked venous
      thromboembolism have a high risk of recurrence after anticoagulants are
      discontinued. Aspirin may be effective in preventing a recurrence of venous
      thromboembolism. METHODS: We randomly assigned 822 patients who had completed
      initial anticoagulant therapy after a first episode of unprovoked venous
      thromboembolism to receive aspirin, at a dose of 100 mg daily, or placebo for up
      to 4 years. The primary outcome was a recurrence of venous thromboembolism.
      RESULTS: During a median follow-up period of 37.2 months, venous thromboembolism
      recurred in 73 of 411 patients assigned to placebo and in 57 of 411 assigned to
      aspirin (a rate of 6.5% per year vs. 4.8% per year; hazard ratio with aspirin,
      0.74; 95% confidence interval [CI], 0.52 to 1.05; P=0.09). Aspirin reduced the
      rate of the two prespecified secondary composite outcomes: the rate of venous
      thromboembolism, myocardial infarction, stroke, or cardiovascular death was
      reduced by 34% (a rate of 8.0% per year with placebo vs. 5.2% per year with
      aspirin; hazard ratio with aspirin, 0.66; 95% CI, 0.48 to 0.92; P=0.01), and the
      rate of venous thromboembolism, myocardial infarction, stroke, major bleeding, or
      death from any cause was reduced by 33% (hazard ratio, 0.67; 95% CI, 0.49 to
      0.91; P=0.01). There was no significant between-group difference in the rates of
      major or clinically relevant nonmajor bleeding episodes (rate of 0.6% per year
      with placebo vs. 1.1% per year with aspirin, P=0.22) or serious adverse events.
      CONCLUSIONS: In this study, aspirin, as compared with placebo, did not
      significantly reduce the rate of recurrence of venous thromboembolism but
      resulted in a significant reduction in the rate of major vascular events, with
      improved net clinical benefit. These results substantiate earlier evidence of a
      therapeutic benefit of aspirin when it is given to patients after initial
      anticoagulant therapy for a first episode of unprovoked venous thromboembolism.
      (Funded by National Health and Medical Research Council [Australia] and others;
      Australian New Zealand Clinical Trials Registry number, ACTRN12605000004662.).

PMID- 23121407
TI  - Pre-existing central nervous system lesions negate cytokine requirements for
      regional experimental autoimmune encephalomyelitis development.
AB  - In region-specific forms of experimental autoimmune encephalomyelitis (EAE),
      lesion initiation is regulated by T-cell-produced interferon-gamma (IFN-gamma)
      resulting in spinal cord disease in the presence of IFN-gamma and cerebellar
      disease in the absence of IFN-gamma. Although this role for IFN-gamma in regional
      disease initiation is well defined, little is known about the consequences of
      previous tissue inflammation on subsequent regional disease, information vital to
      the development of therapeutics in established disease states. This study
      addressed the hypothesis that previous establishment of regional EAE would
      determine subsequent tissue localization of new T-cell invasion and associated
      symptoms regardless of the presence or absence of IFN-gamma production. Serial
      transfer of optimal or suboptimal doses of encephalitogenic IFN-gamma-sufficient
      or -deficient T-cell lines was used to examine the development of new clinical
      responses associated with the spinal cord and cerebellum at various times after
      EAE initiation. Previous inflammation within either cerebellum or spinal cord
      allowed subsequent T-cell driven inflammation within that tissue regardless of
      IFN-gamma presence. Further, T-cell IFN-gamma production after initial lesion
      formation exacerbated disease within the cerebellum, suggesting that IFN-gamma
      plays different roles at different stages of cerebellar disease. For the spinal
      cord, IFN-gamma-deficient cells (that are ordinarily cerebellum disease
      initiators) were capable of driving new spinal-cord-associated clinical symptoms
      more than 60 days after the initial acute EAE resolution. These data suggest that
      previous inflammation modulates the molecular requirements for new
      neuroinflammation development.

PMID- 23121408
TI  - Copper toxicosis in a Boer goat.
AB  - A 1-year-old female Boer goat was presented with a 1-day history of pigmenturia,
      anorexia, and shivering. Anemia was not present initially, but progressive
      hemolytic anemia developed subsequently and was characterized by the finding of
      Heinz bodies in both intact RBCs and in ghost cells and the presence of atypical
      fusiform RBCs. Plasma biochemical analysis revealed increased activities of
      aspartate aminotransferase and gamma-glutamyltransferase, hyperbilirubinemia, and
      azotemia. Histopathologic examination of a liver biopsy revealed necrosis of
      individual hepatocytes and intracytoplasmic rhodamine-positive granules,
      consistent with copper. Copper concentration in ante-mortem hepatic tissue was
      increased, and a diagnosis of copper toxicosis was made. Despite supportive
      therapy, the goat continued to decline and was euthanized. Necropsy findings
      included hepatic necrosis and hemoglobinuric nephrosis. Freshly collected
      specimens of liver and kidney had markedly increased copper concentrations. The
      mineral composition of the water, grass hay, and goat chow was evaluated, and
      toxins and significant mineral imbalances were not found. The underlying cause of
      the hepatic accumulation and subsequent release of copper remains unclear in this
      goat. Recently, Boer goats have been recognized as being prone to copper
      toxicosis and may be more susceptible than other breeds; similar to sheep, Boer
      goats may experience a hemolytic crisis secondary to copper toxicosis.

PMID- 23121409
TI  - Characterization of AQX-1125, a small-molecule SHIP1 activator: Part 2. Efficacy
      studies in allergic and pulmonary inflammation models in vivo.
AB  - BACKGROUND: The efficacy of AQX-1125, a small-molecule SH2-containing inositol-5'
      phosphatase 1 (SHIP1) activator and clinical development candidate, is
      investigated in rodent models of inflammation. EXPERIMENTAL APPROACH: AQX-1125
      was administered orally in a mouse model of passive cutaneous anaphylaxis (PCA)
      and a number of rodent models of respiratory inflammation including: cigarette
      smoke, LPS and ovalbumin (OVA)-mediated airway inflammation. SHIP1 dependency of
      the AQX-1125 mechanism of action was investigated by comparing the efficacy in
      wild-type and SHIP1-deficient mice subjected to an intrapulmonary LPS challenge.
      RESULTS: AQX-1125 exerted anti-inflammatory effects in all of the models studied.
      AQX-1125 decreased the PCA response at all doses tested. Using bronchoalveolar
      lavage (BAL) cell counts as an end point, oral or aerosolized AQX-1125 dose
      dependently decreased the LPS-mediated pulmonary neutrophilic infiltration at 3
      30 mg kg-1 and 0.15-15 MUg kg-1 respectively. AQX-1125 suppressed the OVA
      mediated airway inflammation at 0.1-10 mg kg-1. In the smoke-induced airway
      inflammation model, AQX-1125 was tested at 30 mg kg-1 and significantly reduced
      the neutrophil infiltration of the BAL fluid. AQX-1125 (10 mg kg-1) decreased LPS
      induced pulmonary neutrophilia in wild-type mice but not in SHIP1-deficient mice.
      CONCLUSIONS: The SHIP1 activator, AQX-1125, suppresses leukocyte accumulation and
      inflammatory mediator release in rodent models of pulmonary inflammation and
      allergy. As shown in the mouse model of LPS-induced lung inflammation, the
      efficacy of the compound is dependent on the presence of SHIP1. Pharmacological
      SHIP1 activation may have clinical potential for the treatment of pulmonary
      inflammatory diseases.

PMID- 23121415
TI  - Effects of betamethasone on neuropathic pain in a rat spare nerve injury model.
AB  - The aim of the present study was to examine the effect of glucocorticoids on
      neuropathic pain using a rat spare nerve injury (SNI) model. Eighty rats were
      treated divided into the following groups: (i) a sham-operated group; (ii) a
      group subjected to SNI (S); (iii) a group subjected to SNI and administered 4 MUg
      betamethasone intrathecally (D1); and (iv) a group subjected to SNI and
      administered 1 mg betamethasone at the site of nerve injury (D2). The mechanical
      withdrawal threshold (MWT) and thermal withdrawal duration (TWD) were measured 1
      day before and the 1, 3, 7 and 14 days after SNI. Glial fibrillary acidic
      protein, glucocorticoid receptor (GR), tumour necrosis factor (TNF)-alpha and
      interleukin (IL)-1beta levels in spinal cord tissue were quantified 1, 3, 7 and
      14 days after SNI. The MWT was significantly higher in the D2 compared with S
      group 3-14 days after surgery and compared with the D1 group 7 and 14 days after
      surgery (P < 0.05). The TWD was significantly lower in the D2 group compared with
      the S and D2 groups 3-14 days after surgery (P < 0.05). Glial fibrillary acidic
      protein expression was significantly lower in the D1 and D2 groups compared with
      the S group 3-14 days after surgery (P < 0.05). Glucocorticoid receptor
      expression was significantly higher in the D1 group compared with the S and D2
      groups after surgery (P < 0.05). Levels of TNF-alpha and IL-1beta were
      significantly lower in the D1 and D2 groups compared with the S group at all time
      points after surgery (P < 0.05). Betamethasone suppressed astrocyte activation
      and increases in TNF-alpha and IL-1beta levels in a rat model of neuropathic
      pain. Local injection of betamethasone resulted in smaller increases in spinal GR
      expression and more pronounced improvement in pain behaviour compared with
      intrathecal injection.

PMID- 23121422
TI  - Managing anticoagulation for atrial fibrillation: current issues and future
      strategies.
AB  - Although warfarin is superior to aspirin in reducing the risk of stroke in
      patients with atrial fibrillation, it can increase major bleeds. Hence,
      physicians stratify patients according to stroke risk to ensure a net benefit. In
      this review, the CHA(2) DS(2) -VASc stratification scheme used in the latest
      European Society of Cardiology (2010/12) guidelines will be explained. The
      greater sensitivity of this scheme, compared to the previous CHADS(2) , more
      closely delineates patients for whom warfarin is appropriate. The review also
      anticipates that there will be a wider range of patients who may benefit from the
      new oral anticoagulants, which show similar or superior efficacy and/or safety to
      warfarin with a significant reduction in intracranial haemorrhage and do not
      require routine coagulation monitoring. The role of conventional and new
      anticoagulant options will also be discussed.

PMID- 23121414
TI  - Burns: an update on current pharmacotherapy.
AB  - INTRODUCTION: The worldwide occurrence of burn injuries remains high despite
      efforts to reduce injury incidence through public awareness campaigns and
      improvements in living conditions. In 2004, almost 11 million people experienced
      burns severe enough to warrant medical treatment. Advances over the past several
      decades in aggressive resuscitation, nutrition, excision and grafting have
      reduced morbidity and mortality. Incorporation of pharmacotherapeutics into
      treatment regimens may further reduce complications of severe burn injuries.
      AREAS COVERED: Severe burn injuries, as well as other forms of stress and trauma,
      trigger a hypermetabolic response that, if left untreated, impedes recovery. In
      the past two decades, use of anabolic agents, beta-adrenergic receptor
      antagonists and anti-hyperglycemic agents has successfully counteracted post-burn
      morbidities including catabolism, the catecholamine-mediated response and insulin
      resistance. Here, the authors review the most up-to-date information on currently
      used pharmacotherapies in the treatment of these sequelae of severe burns and the
      insights that have expanded the understanding of the pathophysiology of severe
      burns. EXPERT OPINION: Existing drugs offer promising advances in the care of
      burn injuries. Continued gains in the understanding of the molecular mechanisms
      driving the hypermetabolic response will enable the application of additional
      existing drugs to be broadened to further attenuate the hypermetabolic response.

PMID- 23121423
TI  - Middle cerebral artery blood velocity during running.
AB  - Running induces characteristic fluctuations in blood pressure (BP) of unknown
      consequence for organ blood flow. We hypothesized that running-induced BP
      oscillations are transferred to the cerebral vasculature. In 15 healthy
      volunteers, transcranial Doppler-determined middle cerebral artery (MCA) blood
      flow velocity, photoplethysmographic finger BP, and step frequency were measured
      continuously during three consecutive 5-min intervals of treadmill running at
      increasing running intensities. Data were analysed in the time and frequency
      domains. BP data for seven subjects and MCA velocity data for eight subjects,
      respectively, were excluded from analysis because of insufficient signal quality.
      Running increased mean arterial pressure and mean MCA velocity and induced
      rhythmic oscillations in BP and in MCA velocity corresponding to the difference
      between step rate and heart rate (HR) frequencies. During running, rhythmic
      oscillations in arterial BP induced by interference between HR and step frequency
      impact on cerebral blood velocity. For the exercise as a whole, average MCA
      velocity becomes elevated. These results suggest that running not only induces an
      increase in regional cerebral blood flow but also challenges cerebral
      autoregulation.

PMID- 23121424
TI  - In situ chemical composition analysis of cirrhosis by combining synchrotron
      fourier transform infrared and synchrotron X-ray fluorescence microspectroscopies
      on the same tissue section.
AB  - Liver is subject to various chronic pathologies, progressively leading to
      cirrhosis, which is associated with an increased risk of hepatocellular
      carcinoma. There is an urgent need for diagnostic and prognostic markers of
      chronic liver diseases and liver cancer. Spectroscopy-based approaches can
      provide an overview of the chemical composition of a tissue sample offering the
      possibility of investigating in depth the subtle chemical changes associated with
      pathological states. In this study, we have addressed the composition of
      cirrhotic liver tissue by combining synchrotron Fourier transform infrared (FTIR)
      microspectroscopy and synchrotron micro-X-ray fluorescence (XRF) on the same
      tissue section using a single sample holder in copper. This allowed investigation
      of the in situ biochemical as well as elemental composition of cells and tissues
      at high spatial resolution. Cirrhosis is characterized by regeneration nodules
      surrounded by annular fibrosis. Hepatocytes within cirrhotic nodules were
      characterized by high content in esters and sugars as well as in phosphorus and
      iron compared with fibrotic septa. A high heterogeneity was observed between
      cirrhotic nodules in their content in sugars and iron. On fibrosis, synchrotron
      XRF revealed enrichment in calcium compared to cirrhotic hepatocytes. Careful
      scrutiny of tissue sections led to detection of the presence of microcrystals
      that were demonstrated as precipitates of calcite using synchrotron FTIR. These
      results demonstrated that synchrotron FTIR and synchrotron XRF
      microspectroscopies provide complementary information on the chemical composition
      of cirrhotic hepatocytes and fibrotic septa in cirrhosis.

PMID- 23121425
TI  - Impact of action cues, self-efficacy and perceived barriers on daily foot exam
      practice in type 2 diabetes mellitus patients with peripheral neuropathy.
AB  - AIMS AND OBJECTIVES: To identify the effects of health belief model factors on
      daily foot-exam practice among diabetes mellitus patients with peripheral
      neuropathy. BACKGROUND: Daily foot exams are one of the most important self-care
      behaviours that prevent the occurrence of diabetic foot ulcers and subsequent
      amputation. Although daily foot exams were under-practiced in patients with
      peripheral neuropathy, few studies have explored modifiable social-psychological
      factors related to daily foot exams. DESIGN: A cross-sectional survey was used to
      collect the data. METHODS: A total of 277 patients with diabetes and peripheral
      neuropathy were recruited from two hospitals in northern Taiwan. The Family APGAR
      and Diabetic Foot Ulcer Health Belief Scale (DFUHBS) were used to measure family
      support and health belief factors respectively. Data on foot-exam practice,
      perceived self-efficacy and action cues were collected through the use of
      structured questionnaires. The data were analysed using logistic regression.
      RESULT: The regression model revealed that select action cues (recommendations
      from family, friends, or health professionals), perceived self-efficacy and
      perceived barriers interactively influenced the participants' daily foot-exam
      practice. CONCLUSION: Factors related to daily foot-exam practice were
      identified. Specifically, action cues played a significant role in motivating
      daily foot-exam practice in this group. RELEVANCE TO CLINICAL PRACTICE: This
      study recognises modifiable factors that influence the daily foot-exam practice
      of patients with diabetes and peripheral neuropathy. Using the findings of this
      study, health professionals can design interventions that aim to modify the above
      factors as a means to promote daily foot-exam practice.

PMID- 23121426
TI  - Removable esophageal stents have poor efficacy for the treatment of refractory
      benign esophageal strictures (RBES).
AB  - With the recent availability of removable esophageal stents, endoscopic stenting
      has been utilized to treat refractory benign esophageal strictures (RBES). The
      objective of this study was to review the feasibility and effectiveness of
      removable esophageal stents to treat RBES. Patients who received removable
      esophageal stents for the treatment of RBES at the institution between 2004-2010
      using its stent implantation logs and endoscopic database were retrospectively
      identified. Patient demographics, stricture etiology and location, stent and
      procedure characteristics, and clinical outcomes were obtained. Twenty-five
      patients with a mean age of 70 (72% male) underwent initial stent placement; 24
      were successful. Overall clinical success was achieved in five of the 19 patients
      (26%) ultimately undergoing stent removal. RBES etiologies included anastomotic
      (13), radiation (5), peptic (3), chemotherapy (1), scleroderma (1), and unknown
      (2). Alimaxx-E (Merit-Endotek, South Jordan, UT, USA) stents were placed in 20
      patients and Polyflex (Boston Scientific, Natick, MA, USA) stents were used in
      five patients. Immediate complications included failed deployment (1) and chest
      pain (7). Five patients died prior to stent removal. Stent migration was found in
      53% (10/19) of patients who underwent stent removal: nine required additional
      therapy and one had symptom resolution. Out of the nine patients without stent
      migration, five required additional therapy and four had symptom resolution.
      Although placement of removable esophageal stents for RBES is technically
      feasible, it is frequently complicated by stent migration and chest pain. In
      addition, few patients achieved long-term stricture resolution after initial
      stenting. In this study, most patients ultimately required repeated stenting
      and/or dilations to maintain relief of dysphagia. 

PMID- 23121428
TI  - Mild traumatic brain injury.

PMID- 23121427
TI  - Nuclear magnetic resonance solution structure of an N(2)-guanine DNA adduct
      derived from the potent tumorigen dibenzo[a,l]pyrene: intercalation from the
      minor groove with ruptured Watson-Crick base pairing.
AB  - The most potent tumorigen identified among the polycyclic aromatic hydrocarbons
      (PAH) is the nonplanar fjord region dibenzo[a,l]pyrene (DB[a,l]P). It is
      metabolically activated in vivo through the widely studied diol epoxide (DE)
      pathway to form covalent adducts with DNA bases, predominantly guanine and
      adenine. The (+)-11S,12R,13R,14S DE enantiomer forms adducts via its C14 position
      with the exocyclic amino group of guanine. Here, we present the first nuclear
      magnetic resonance solution structure of a DB[a,l]P-derived adduct, the 14R-(+)
      trans-anti-DB[a,l]P-N(2)-dG (DB[a,l]P-dG) lesion in double-stranded DNA. In
      contrast to the stereochemically identical benzo[a]pyrene-derived N(2)-dG adduct
      (B[a]P-dG) in which the B[a]P rings reside in the B-DNA minor groove on the 3'
      side of the modifed deoxyguanosine, in the DB[a,l]P-derived adduct the DB[a,l]P
      rings intercalate into the duplex on the 3'-side of the modified base from the
      sterically crowded minor groove. Watson-Crick base pairing of the modified
      guanine with the partner cytosine is broken, but these bases retain some stacking
      with the bulky DB[a,l]P ring system. This new theme in PAH DE-DNA adduct
      conformation differs from (1) the classical intercalation motif in which Watson
      Crick base pairing is intact at the lesion site and (2) the base-displaced
      intercalation motif in which the damaged base and its partner are extruded from
      the helix. The structural considerations that lead to the intercalated
      conformation of the DB[a,l]P-dG lesion in contrast to the minor groove alignment
      of the B[a]P-dG adduct, and the implications of the DB[a,l]P-dG conformational
      motif for the recognition of such DNA lesions by the human nucleotide excision
      repair apparatus, are discussed.

PMID- 23121429
TI  - Lack of functionality and need for revision of an Ommaya reservoir placed into a
      cavum septum pellucidum.
AB  - Ommaya reservoirs are routinely placed for the administration of intrathecal
      chemotherapy or antibiotics. There is scant literature that addresses the
      functionality of an Ommaya catheter placed exclusively within a cavum septum
      pellucidum (CSP). In this case, the authors placed an Ommaya reservoir in a 30
      year-old man with Burkitt lymphoma in the CNS for intrathecal chemotherapy. The
      catheter tip was placed within a large CSP. The authors demonstrated failure of
      the system by injecting contrast agent into the reservoir and obtaining immediate
      and delayed CT scans that failed to demonstrate contrast dissemination into the
      ventricular system. An Ommaya reservoir placed exclusively within a CSP is
      potentially not functional, and can be dangerous if used for intrathecal drug
      therapy.

PMID- 23121430
TI  - Glycerol rhizotomy and radiofrequency thermocoagulation for trigeminal neuralgia
      in multiple sclerosis.
AB  - OBJECT: Patients with trigeminal neuralgia due to multiple sclerosis (TN-MS) and
      idiopathic TN (ITN) who underwent glycerol rhizotomy (GR) and radiofrequency
      thermocoagulation with glycerol rhizotomy (RFTC-GR) were compared to investigate
      the effectiveness of these percutaneous ablative procedures in the TN-MS
      population. METHODS: Between 1998 and 2010, 822 patients with typical TN were
      evaluated; 63 (8%) had TN-MS and 759 (92%) had ITN. Pain relief comparisons were
      made between 22 GR procedures in patients with TN-MS and 470 GR procedures in
      patients with ITN; 50 RFTC-GR procedures in patients with TN-MS and 287 RFTC-GR
      procedures in patients with ITN were compared. Analysis of time to recurrence
      included only procedures that achieved complete pain relief without medications.
      RESULTS: After 15 of the GR procedures (68%) in patients with TN-MS and 315 of
      the procedures (67%) in those with ITN, the patients were pain free without
      medications (p = 0.736). After 36 of the RFTC-GR procedures (72%) in patients
      with TN-MS and 210 of the procedures (73%) in those with ITN, the patients were
      pain free without medications (p = 0.657). The difference in pain relief between
      GR and RFTC-GR for patients with TN-MS was not significant (p = 0.447). The
      median time to failure of GR was 20 months in patients with TN-MS compared with
      25 months in those with ITN (p = 0.403). The median time to failure of RFTC-GR
      was 26 months in the TN-MS population compared with 21 months in the ITN
      population (p = 0.449). Patients with TN-MS experienced similar times to
      recurrence whether they were treated with GR or RFTC-GR (p = 0.431). CONCLUSIONS:
      Pain relief and durability of relief outcomes of GR and RFTC-GR were similar in
      patients with TN-MS and ITN, reinforcing their use as preferred treatments of TN
      MS. The GR and RFTC-GR achieved comparable outcomes in patients with TN-MS,
      suggesting that both can be used to good effect.

PMID- 23121431
TI  - Clinical features and functional recovery of traumatic isolated oculomotor nerve
      palsy in mild head injury with sphenoid fracture.
AB  - OBJECT: The aim of this study was to provide information about long-term
      functional outcome in patients with isolated oculomotor nerve palsy following
      minor head injury and to discuss surgical treatment of these patients, especially
      those with accompanying sphenoid fracture. METHODS: A retrospective analysis was
      made of 26 patients with traumatic isolated oculomotor nerve palsy. The severity
      of oculomotor nerve palsy and the functional recovery were evaluated based on
      extraocular muscle movement, eyelid movement, and pupil size. On average,
      patients were evaluated 3.6 days after the initial injury, and the average follow
      up period was 14.2 months (range 3 months-2 years). RESULTS: Twenty men and six
      women were enrolled in this study. The most common cause of trauma was motor
      vehicle accident in 17 (65.4%) of 26. Among all the recorded symptoms, internal
      ophthalmoplegia was most frequently seen. The recovery rates of ptosis, external
      ophthalmoplegia, and internal ophthalmoplegia were 95% (19 of 20 patients), 83.3%
      (15 of 18 patients), and 50% (13 of 26 patients), respectively. The 6 patients
      with sphenoid fracture underwent surgical decompression of the superior orbital
      fissure, after which all patients experienced recovery from ptosis and external
      ophthalmoplegia and 66.7% (4 of 6 patients) recovered from internal
      ophthalmoplegia. CONCLUSIONS: Limited eye movement may be a major factor that
      negatively affects functional recovery after mild head injury. Sphenoid fracture
      might be one of the potential mechanisms involved in traumatic isolated
      oculomotor nerve palsy after mild head injury. Surgical decompression should be
      considered when there is evidence of bone compression of the superior orbital
      fissure.

PMID- 23121432
TI  - Failed awake craniotomy: a retrospective analysis in 424 patients undergoing
      craniotomy for brain tumor.
AB  - OBJECT: Awake craniotomy for removal of intraaxial tumors within or adjacent to
      eloquent brain regions is a well-established procedure. However, awake craniotomy
      failures have not been well characterized. In the present study, the authors
      aimed to analyze and assess the incidence and causes for failed awake craniotomy.
      METHODS: The database of awake craniotomies performed at Tel Aviv Medical Center
      between 2003 and 2010 was reviewed. Awake craniotomy was considered a failure if
      conversion to general anesthesia was required, or if adequate mapping or
      monitoring could not have been achieved. RESULTS: Of 488 patients undergoing
      awake craniotomy, 424 were identified as having complete medical, operative, and
      anesthesiology records. The awake craniotomies performed in 27 (6.4%) of these
      424 patients were considered failures. The main causes of failure were lack of
      intraoperative communication with the patient (n = 18 [4.2%]) and/or
      intraoperative seizures (n = 9 [2.1%]). Preoperative mixed dysphasia (p < 0.001)
      and treatment with phenytoin (p = 0.0019) were related to failure due to lack of
      communication. History of seizures (p = 0.03) and treatment with multiple
      antiepileptic drugs (p = 0.0012) were found to be related to failure due to
      intraoperative seizures. Compared with the successful awake craniotomy group, a
      significantly lower rate of gross-total resection was achieved (83% vs 54%, p =
      0.008), there was a higher incidence of short-term speech deterioration
      postoperatively (6.1% vs 23.5%, p = 0.0017) as well as at 3 months
      postoperatively (2.3% vs 15.4%, p = 0.0002), and the hospitalization period was
      longer (4.9 +/- 6.2 days vs 8.0 +/- 10.1 days, p < 0.001). Significantly more
      major complications occurred in the failure group (4 [14.8%] of 27) than in the
      successful group (16 [4%] of 397) (p = 0.037). CONCLUSIONS: Failures of awake
      craniotomy were associated with a lower incidence of gross-total resection and
      increased postoperative morbidity. The majority of awake craniotomy failures were
      preventable by adequate patient selection and avoiding side effects of drugs
      administered during surgery.

PMID- 23121433
TI  - Antibacterial therapeutic drug monitoring in cerebrospinal fluid: difficulty in
      achieving adequate drug concentrations.
AB  - This report illustrates the difficulty in managing CNS infection in neurosurgical
      patients, the altered drug pharmacokinetics associated with critical illness, and
      the role that therapeutic drug monitoring (TDM) of CSF can play in assisting
      clinical decision making.   The authors present a case of external ventricular
      drain-related ventriculitis in a critically ill patient who initially presented
      with a subarachnoid hemorrhage. They discuss the physiological changes found in
      such patients, in particular augmented renal clearance (demonstrated in this
      patient by a measured creatinine clearance of 375 ml/min/1.73 m(2)), noting the
      effect this had on drug pharmacokinetics and leading to dosing requirements 2-3
      times those recommended in standard regimens.   The authors consider the
      bacterial "kill" characteristics of 2 different antibacterial agents (meropenem
      and vancomycin) and describe the unique approach of using plasma and CSF TDM to
      achieve optimal drug exposure at the site of infection while limiting toxic side
      effects. The authors demonstrate that simply using plasma TDM as a surrogate
      marker for drug concentration in the CNS may lead to underdosing, exemplified in
      this patient by CSF vancomycin concentrations as little as 13% of that in plasma.
      Finally, by measuring CSF and plasma ratios, the authors illustrate the disparity
      in pharmacokinetic properties between drugs, reminding the clinician of the
      importance of CNS penetration when selecting antibacterial agents in such cases. 
      This work raises an important hypothesis in the accurate prescription of
      antibacterial agents in neurosurgical critical care, namely underdosing in the
      context of augmented elimination and impaired target site penetration. However,
      prior to any recommendations regarding empirical dose modification, more data are
      clearly needed, particularly with respect to the safety and efficacy of such an
      approach. In this respect, the authors would advocate further research using TDM
      in the management of CNS infection in this setting, in addition to work defining
      plasma and CSF concentrations associated with antibacterial efficacy and
      toxicity.

PMID- 23121434
TI  - Validation of the surgical Apgar score in a neurosurgical patient population.
AB  - OBJECT: The surgical Apgar score (SAS) reliably predicts postoperative death and
      complications and has been validated in a large cohort of general and vascular
      surgery patients. However, there has been limited study of the utility of the
      score in the neurosurgical population. The authors tested the hypothesis that the
      SAS would predict postoperative complications and length of stay after
      neurosurgical procedures. METHODS: A cohort of 918 intracranial and spine surgery
      patients treated over a 3-year period were retrospectively evaluated. The 10
      point SAS was calculated and postoperative 30-day mortality and complications
      rates, intensive care unit (ICU) stay, and hospital stay were assessed by 2
      independent raters. Univariate analysis and multivariate logistic regression were
      performed. RESULTS: There were 145 patients (15.8%) with at least 1 complication
      and 24 patients (2.6%) who died within 30 days of surgery. Surgical Apgar scores
      were significantly associated with the likelihood of postoperative complications
      (p < 0.001) and death (p = 0.002); scores varied inversely with postoperative
      complication and mortality risk in a multivariate analysis. Low SASs also
      predicted prolonged ICU and hospital stay. Patients with scores of 0-2 stayed a
      mean of 18.9 days (p < 0.001) and patients with scores of 3-4 stayed an average
      of 14.3 days (p < 0.001) compared with 4.1 days in patients with scores of 9-10.
      CONCLUSIONS: The application of the surgical Apgar score to a neurosurgical
      cohort predicted 30-day postoperative mortality and complication rates as well as
      extended ICU and hospital stay. This readily calculated score may help
      neurosurgical teams efficiently direct postoperative care to those at highest
      risk of death and complications.

PMID- 23121435
TI  - Motor evoked potential monitoring of the vagus nerve with transcranial electrical
      stimulation during skull base surgeries.
AB  - OBJECT: Dysphasia is one of the most serious complications of skull base
      surgeries and results from damage to the brainstem and/or cranial nerves involved
      in swallowing. Here, the authors propose a method to monitor the function of the
      vagus nerve using endotracheal tube surface electrodes and transcranial
      electrical stimulation during skull base surgeries. METHODS: Fifteen patients
      with skull base or brainstem tumors were enrolled. The authors used surface
      electrodes of an endotracheal tube to record compound electromyographic responses
      from the vocalis muscle. Motor neurons were stimulated using corkscrew electrodes
      placed subdermally on the scalp at C3 and C4. During surgery, the operator
      received a warning when the amplitude of the vagal motor evoked potential (MEP)
      decreased to less than 50% of the control level. After surgery, swallowing
      function was assessed clinically using grading criteria. RESULTS: In 5 patients,
      vagal MEP amplitude permanently deteriorated to less than 50% of the control
      level on the right side when meningiomas were dissected from the pons or basilar
      artery, or when a schwannoma was dissected from the vagal rootlets. These 5
      patients had postoperative dysphagia. At 4 weeks after surgery, 2 patients still
      had dysphagia. In 2 patients, vagal MEPs of one side transiently disappeared when
      the tumors were dissected from the brainstem or the vagal rootlets. After
      surgery, both patients had dysphagia, which recovered in 4 weeks. In 7 patients,
      MEP amplitude was consistent, maintaining more than 50% of the control level
      throughout the operative procedures. After surgery all 7 patients were
      neurologically intact with normal swallowing function. CONCLUSIONS: Vagal MEP
      monitoring with transcranial electrical stimulation and endotracheal tube
      electrode recording was a safe and effective method to provide continuous real
      time information on the integrity of both the supranuclear and infranuclear vagal
      pathway. This method is useful to prevent intraoperative injury of the brainstem
      corticobulbar tract or the vagal rootlets and to avoid the postoperative
      dysphagia that is often associated with brainstem or skull base surgeries.

PMID- 23121436
TI  - Reproducibility of an objective four-choice canine vision testing technique that
      assesses vision at differing light intensities.
AB  - OBJECTIVE: The increasing importance of canine retinal dystrophy models means
      accurate vision testing is needed. This study was performed to evaluate a four
      choice vision testing technique for any difference in outcome measures with
      repeated evaluations of the same dogs. ANIMALS STUDIED:   Four 11-month-old RPE65
      deficient dogs. PROCEDURES: Vision was evaluated using a previously described
      four-choice vision testing device. Four evaluations were performed at 2-week
      intervals. Vision was assessed at six different white light intensities (bright
      through dim), and each eye was evaluated separately. The ability to select the
      one of the four exit tunnels that was open at the far end was assessed ('choice
      of exit') and recorded as correct or incorrect first tunnel choice. 'Time to
      exit' the device was also recorded. Both outcomes were analyzed for significance
      using anova. We hypothesized that performance would improve with repeated testing
      (more correct choices and more rapid time to exit). RESULTS: 'Choice of exit' did
      not vary significantly between each evaluation (P = 0.12), in contrast 'time to
      exit' increased significantly (P = 0.012), and showed greater variability in dim
      light conditions. CONCLUSIONS: We found no evidence to support the hypothesis
      that either measure of outcome worsened with repeated testing; in fact, the 'time
      to exit' outcome worsened rather than improved. The 'choice of exit' gave
      consistent results between trials. These outcome data indicate the importance of
      including a choice-based assessment of vision in addition to measurement of
      device transit time.

PMID- 23121437
TI  - Arrhythmogenic risk of pulmonary artery catheterisation in patients with severe
      aortic stenosis undergoing transcatheter aortic valve implantation.
AB  - Many clinicians consider severe aortic stenosis to be a contraindication to
      pulmonary artery catheterisation, except during open heart surgery with
      cardiopulmonary bypass. This is due to the perceived high risk of arrhythmia,
      although the true incidence of ventricular tachycardia and fibrillation remains
      unclear. We conducted a retrospective study to estimate the incidence of severe
      arrhythmias during pulmonary artery catheterisation in 380 patients with severe
      aortic stenosis scheduled for transcatheter aortic valve implantation.
      Ventricular fibrillation was seen in only one patient (0.26%), and this was
      successfully terminated by external defibrillation. No episodes of ventricular
      tachycardia were recorded and there were also no arrhythmias during removal of
      the catheter. We have therefore concluded that pulmonary artery catheterisation
      in patients with severe aortic stenosis is not associated with a high incidence
      of ventricular fibrillation or tachycardia, allowing pulmonary artery pressure
      monitoring to be performed relatively safely in such patients.

PMID- 23121438
TI  - A major new step in non-invasive evaluation of portal hypertension: elastography.

PMID- 23121439
TI  - Bedside monitoring to adjust antiplatelet therapy for coronary stenting.
AB  - BACKGROUND: Patients' responses to oral antiplatelet therapy are subject to
      variation. Bedside monitoring offers the opportunity to improve outcomes after
      coronary stenting by individualizing therapy. METHODS: We randomly assigned 2440
      patients scheduled for coronary stenting at 38 centers to a strategy of platelet
      function monitoring, with drug adjustment in patients who had a poor response to
      antiplatelet therapy, or to a conventional strategy without monitoring and drug
      adjustment. The primary end point was the composite of death, myocardial
      infarction, stent thrombosis, stroke, or urgent revascularization 1 year after
      stent implantation. For patients in the monitoring group, the VerifyNow P2Y12 and
      aspirin point-of-care assays were used in the catheterization laboratory before
      stent implantation and in the outpatient clinic 2 to 4 weeks later. RESULTS: In
      the monitoring group, high platelet reactivity in patients taking clopidogrel
      (34.5% of patients) or aspirin (7.6%) led to the administration of an additional
      bolus of clopidogrel, prasugrel, or aspirin along with glycoprotein IIb/IIIa
      inhibitors during the procedure. The primary end point occurred in 34.6% of the
      patients in the monitoring group, as compared with 31.1% of those in the
      conventional-treatment group (hazard ratio, 1.13; 95% confidence interval [CI],
      0.98 to 1.29; P=0.10). The main secondary end point, stent thrombosis or any
      urgent revascularization, occurred in 4.9% of the patients in the monitoring
      group and 4.6% of those in the conventional-treatment group (hazard ratio, 1.06;
      95% CI, 0.74 to 1.52; P=0.77). The rate of major bleeding events did not differ
      significantly between groups. CONCLUSIONS: This study showed no significant
      improvements in clinical outcomes with platelet-function monitoring and treatment
      adjustment for coronary stenting, as compared with standard antiplatelet therapy
      without monitoring. (Funded by Allies in Cardiovascular Trials Initiatives and
      Organized Networks and others; ARCTIC ClinicalTrials.gov number, NCT00827411.).

PMID- 23121440
TI  - Physical performance and subjective ratings after a soccer-specific exercise
      simulation: comparison of natural grass versus artificial turf.
AB  - This study aimed to compare the recovery kinetics of physical performance and
      subjective ratings in response to a soccer-specific exercise simulation on
      natural grass and artificial turf. Physical performance tests and subjective
      ratings were assessed on 13 professional soccer players before, immediately
      after, 24 h and 48 h after the test. Physical performance tests included squat
      jump, countermovement jump, 6-s sprint on a non-motorised treadmill and
      isokinetic eccentric hamstring assessment (2.09 rad . s(-1)). Hamstring peak
      torque decrement was higher (P < 0.05) on natural grass than on artificial turf
      immediately (-4.0%, CI 95%: -10.0 to 2.0%, effect size [ES] = 0.29), 24 h (-3.1%,
      CI 95%: -9.3 to 3.1%, ES = 0.29) and 48 h (-3.8%, CI 95%: -8.5 to 0.9%, ES =
      0.43) after the test. Squat jump performance decrement was significantly lower (P
      < 0.05) on natural grass than artificial turf 48 h after the test (+3.7%, CI 95%:
      1.1 to 6.3%, ES = 0.40). Sprint performance showed no change from baseline
      performance for both trials throughout the protocol. No significant interaction
      between surface and time was found for countermovement jump and subjective
      ratings. These results suggest that a one-off exercise on artificial turf does
      not induce greater fatigue nor does it delay the recovery process when compared
      to natural grass among regular artificial turf players.

PMID- 23121442
TI  - Psychometric evaluation of a Swedish Self-Efficacy scale and Recovery Locus of
      Control scale in the context of minor illness.
AB  - Reliable and valid instruments are essential when examining the role of self
      efficacy and locus of control in the self-care context. The aim of this study was
      to test the validity and reliability of the Self-Efficacy Scale in Self-Care
      (SESSC) and the Swedish version of the Recovery Locus of Control scale (RLoC) in
      the context of minor illness. A descriptive correlational design was used to
      assess the psychometric characteristics of the scales. The study population was
      317 randomly selected Swedish inhabitants aged 18-80. The results from this study
      showed that the RLoC has limitations in reliability and validity and should not
      be applied in the context of self-care of minor illness. The SESSC proved to be a
      reliable and valid instrument in assessing self-efficacy in self-care for minor
      illness. 

PMID- 23121443
TI  - Slow gold adatom diffusion on graphene: effect of silicon dioxide and hexagonal
      boron nitride substrates.
AB  - We examine the nucleation kinetics of Au clusters on graphene and explore the
      relationship with layer number and underlying supporting substrate of graphene.
      Using the mean field theory of diffusion-limited aggregation, morphology patterns
      are semiquantitatively analyzed to obtain Au adatom effective diffusion constants
      and activation energies. Under specified assumptions, the Au adatom diffusion
      constant for single-layer graphene supported on SiO2 is ~50 times smaller than
      that for hexagonal boron nitride (h-BN)-supported graphene and on the order of
      800 times smaller than that for multilayer graphite. Bilayer graphene on SiO2
      shows a Au adatom diffusion constant similar to single-layer graphene on h-BN.
      Scanning probe data show that single-layer graphene is far flatter on h-BN than
      on SiO2. Two factors are proposed as contributing to the observed lower diffusion
      constants on single-layer graphene: local surface roughness and homogeneous loss
      of dispersion/van der Waals electronic stability in multilayers. Graphene Raman
      spectroscopy shows little charge transfer between Au nanoparticles and graphene.

PMID- 23121441
TI  - Fisetin: a dietary antioxidant for health promotion.
AB  - SIGNIFICANCE: Diet-derived antioxidants are now being increasingly investigated
      for their health-promoting effects, including their role in the chemoprevention
      of cancer. In general, botanical antioxidants have received much attention, as
      they can be consumed for longer periods of time without any adverse effects.
      Flavonoids are a broadly distributed class of plant pigments that are regularly
      consumed in the human diet due to their abundance. One such flavonoid, fisetin
      (3,3',4',7-tetrahydroxyflavone), is found in various fruits and vegetables, such
      as strawberry, apple, persimmon, grape, onion, and cucumber. RECENT ADVANCES:
      Several studies have demonstrated the effects of fisetin against numerous
      diseases. It is reported to have neurotrophic, anticarcinogenic, anti
      inflammatory, and other health beneficial effects. CRITICAL ISSUES: Although
      fisetin has been reported as an anticarcinogenic agent, further in-depth in vitro
      and in vivo studies are required to delineate the mechanistic basis of its
      observed effects. In this review article, we describe the multiple effects of
      fisetin with special emphasis on its anticancer activity as investigated in cell
      culture and animal models. FUTURE DIRECTIONS: Additional research focused toward
      the identification of molecular targets could lead to the development of fisetin
      as a chemopreventive/chemotherapeutic agent against cancer and other diseases.

PMID- 23121444
TI  - New Markov-autocorrelation indices for re-evaluation of links in chemical and
      biological complex networks used in metabolomics, parasitology, neurosciences,
      and epidemiology.
AB  - The development of new methods for the computational re-evaluation of links in
      chemical and biological complex networks is very important to save time and
      resources. The Moreau-Broto autocorrelation indices (MBis) are well-known
      topological indices (TIs) used in QSAR/QSPR studies to encode the structural
      information contained in molecular graphs. In addition, MBis and similar
      autocorrelation measures have been used to study other systems like, for example,
      proteins. In the present work, MBis are combined with Markov chains to develop a
      general class of stochastic MBis of order k (MB(k)) that is used to encode the
      structural information contained in different types of large complex networks.
      The MB(k) values obtained for the nodes (centralities) of these networks are used
      as input variables to seek QSPR-like equations (by means of linear discriminant
      analysis) in which the outputs are numerical scores S(L(ij)) that allow us to
      discriminate between connected and nonconnected nodes and therefore re-evaluate
      the connectivity of the whole network. The models developed in this work produced
      the following results in terms of overall accuracy for network reconstruction:
      metabolic networks (72.10%), parasite-host networks (88.70%), CoCoMac brain
      cortex coactivation network (81.89%), and fasciolosis spreading network (86.39%).

PMID- 23121446
TI  - A test of the testing effect: acquiring problem-solving skills from worked
      examples.
AB  - The "testing effect" refers to the finding that after an initial study
      opportunity, testing is more effective for long-term retention than restudying.
      The testing effect seems robust and is a finding from the field of cognitive
      science that has important implications for education. However, it is unclear
      whether this effect also applies to the acquisition of problem-solving skills,
      which is important to establish given the key role problem solving plays in, for
      instance, math and science education. Worked examples are an effective and
      efficient way of acquiring problem-solving skills. Forty students either only
      studied worked examples (SSSS) or engaged in testing after studying an example by
      solving an isomorphic problem (STST). Surprisingly, results showed equal
      performance in both conditions on an immediate retention test after 5 min, but
      the SSSS condition outperformed the STST condition on a delayed retention test
      after 1 week. These findings suggest the testing effect might not apply to
      acquiring problem-solving skills from worked examples.

PMID- 23121445
TI  - Characterization of AQX-1125, a small-molecule SHIP1 activator: Part 1. Effects
      on inflammatory cell activation and chemotaxis in vitro and pharmacokinetic
      characterization in vivo.
AB  - BACKGROUND: The SH2-containing inositol-5'-phosphatase 1 (SHIP1) metabolizes
      PI(3,4,5)P3 to PI(3,4)P2. SHIP1-deficient mice exhibit progressive inflammation.
      Pharmacological activation of SHIP1 is emerging as a potential therapy for
      pulmonary inflammatory diseases. Here we characterize the efficacy of AQX-1125, a
      small-molecule SHIP1 activator currently in clinical development. EXPERIMENTAL
      APPROACH: The effects of AQX-1125 were tested in several in vitro assays: on
      enzyme catalytic activity utilizing recombinant human SHIP1, on Akt
      phosphorylation in SHIP1-proficient and SHIP1-deficient cell lines, on cytokine
      release in murine splenocytes, on human leukocyte chemotaxis using modified
      Boyden chambers and on beta-hexosaminidase release from murine mast cells. In
      addition, pharmacokinetic and drug distribution studies were performed in rats
      and dogs. RESULTS: AQX-1125 increased the catalytic activity of human recombinant
      SHIP1, an effect, which was absent after deletion of the C2 region. AQX-1125
      inhibited Akt phosphorylation in SHIP1-proficient but not in SHIP1-deficient
      cells, reduced cytokine production in splenocytes, inhibited the activation of
      mast cells and inhibited human leukocyte chemotaxis. In vivo, AQX-1125 exhibited
      >80% oral bioavailability and >5 h terminal half-life. CONCLUSIONS: Consistent
      with the role of SHIP1 in cell activation and chemotaxis, the SHIP1 activator AQX
      1125 inhibits Akt phosphorylation, inflammatory mediator production and leukocyte
      chemotaxis in vitro. The in vitro effects and the pharmacokinetic properties of
      the compound make it a suitable candidate for in vivo testing in various models
      of inflammation.

PMID- 23121447
TI  - Ablation of the cellular prion protein, PrPC, specifically on follicular
      dendritic cells has no effect on their maturation or function.
AB  - Follicular dendritic cells (FDC) are situated in the primary follicles of
      lymphoid tissues where they maintain the structural integrity of the B-lymphocyte
      follicle, and help to drive immunoglobulin class-switch recombination, somatic
      hypermutation and affinity maturation during the germinal centre response. FDC
      can also provide a reservoir for pathogens that infect germinal centres including
      HIV and prions. FDC express high levels of the normal cellular form of the prion
      protein (PrP(C) ), which makes them susceptible to prion infection. The function
      of PrP(C)  is uncertain and it is not known why FDC require such high levels of
      expression of a protein that is found mainly on cells of the central nervous
      system. In this study, the function of FDC was assessed in mice that had PrP(C) 
      ablated specifically in their FDC. In mice with FDC-specific PrP(C)  ablation,
      our analysis revealed no observable deficits in lymphoid follicle
      microarchitecture and FDC status. No effects on FDC ability to trap immune
      complexes or drive antigen-specific antibody responses and affinity maturation in
      B lymphocytes were observed. These data clearly demonstrate that PrP(C) 
      expression is dispensable for the functional maturation of FDC and their ability
      to maintain antigen-specific antibody responses and affinity maturation.

PMID- 23121448
TI  - Should  ranolazine  be used for all patients with ischemic heart disease or only
      for symptomatic patients with stable angina or for those with refractory angina
      pectoris? A critical appraisal.
AB  - INTRODUCTION: Ranolazine is a novel antianginal and anti-ischemic agent, that,
      unlike other available antianginal drugs in the United States (beta-blockers,
      organic nitrates, and calcium channel blockers), has no significant effect on
      either heart rate or blood pressure. Its exact mechanism of action is unknown.
      Ranolazine does increase electrocardiographic QTc interval in a dose-related
      manner, but at therapeutic doses it has no proarrhythmic effects. Ranolazine (ER)
      at doses of 500 and 1,000 mg twice daily is currently approved for the treatment
      of angina pectoris either as monotherapy or added to beta-blockers, nitrates, and
      calcium channel blockers. Ranolazine (ER) is currently not approved for the
      treatment of unstable angina, silent ischemia, or cardiac arrhythmias. The most
      common adverse effects reported in clinical trials during ranolazine (ER)
      treatment are dizziness, headaches, constipation, and nausea. AREAS COVERED:
      Recent changes in ranolazine (ER) labeling have led to its increased use for
      treating patients with ischemic heart disease. This review addresses its
      appropriate use. All publications were reviewed and those relevant were included.
      EXPERT OPINION: Ranolazine (ER) is an effective antianginal and anti-ischemic
      agent, but I restrict its use to treat patients with stable angina pectoris.

PMID- 23121449
TI  - Vitamin D status, left ventricular geometric abnormalities and cardiovascular
      disease.

PMID- 23121455
TI  - Symptomatic diffuse esophageal spasm as a major ictal manifestation of post
      traumatic epilepsy: a case report.
AB  - Post-traumatic epilepsy (PTE) can create diagnostic confusion when typical
      epileptic seizures are not manifest. Abdominal symptoms as a manifestation of PTE
      are rare in this setting. We present a 43-year-old female with paroxysmal chest
      and abdominal pain, nausea, salivation, and intermittent dysphagia. Esophageal
      testing demonstrated diffuse esophageal spasm, but smooth muscle relaxants
      provided no relief. Finally, after history revealed that a motor vehicle accident
      temporally preceded symptom onset, video electroencephalography confirmed PTE.
      Therapy with anti-epileptic drug completely resolved symptoms, and the esophageal
      motor pattern normalized. We speculate that abnormal epileptiform discharges from
      the seizure focus altered cerebral input to intrinsic esophageal innervation,
      resulting in inhibitory dysfunction and a picture resembling diffuse esophageal
      spasm. This is the first report of symptomatic esophageal spasm as a major ictal
      manifestation of PTE.

PMID- 23121456
TI  - Determination of the H isotopic composition of individual components in fine
      scale mixtures of organic matter and phyllosilicates with the nanoscale secondary
      ion mass spectrometry.
AB  - When organic matter is mixed on a nanometer scale with clay minerals, the
      individual D/H ratios of the two H-bearing phases cannot be directly measured
      even with the nominal spatial resolution of nanoscale secondary ion mass
      spectrometry (NanoSIMS, 50-100 nm). To overcome this limitation, a new analytical
      protocol is proposed based on the deconvolution of the D(-)/H(-) and (16)OD(
      )/(16)OH(-) ionic ratios measured by NanoSIMS. Indeed, since the yields of H(-)
      and (16)OH(-) are different for organics and clays, it should be theoretically
      possible to determine the mixing ratio of these two components in the area
      analyzed by the ion probe. Using organics with different D/H ratios, the
      interdependence of the D(-)/H(-) and (16)OD(-)/(16)OH(-) ionic ratios was
      determined in pure samples. Then using the H(-) and (16)OH(-) yields and the
      isotopic ratios measured on pure organic matter and clays, the expected D(-)/H(-)
      and (16)OD(-)/(16)OH(-) variations as a function of the mixing proportions were
      determined. These numerical predictions are consistent with measurements on
      laboratory prepared mixtures of D-rich organic matter and D-poor phyllosilicates,
      validating both the proposed experimental protocol and its use for meteorites.
      With an improvement of the precision of the ionic ratios by a factor of 10, it
      should possible to expend this protocol to samples having natural terrestrial D/H
      variations. Such an improvement could be attainable with the development of
      synthetic deuterated reference samples.

PMID- 23121457
TI  - Histometric analysis of the effect of enamel matrix derivative on the healing of
      periodontal defects in rats with diabetes.
AB  - BACKGROUND: Diabetes mellitus (DM) involves metabolic changes that can negatively
      influence periodontal tissues, resulting in impaired periodontal repair. There is
      a lack of information about the outcomes of regenerative approaches under the
      influence of DM. Enamel matrix derivatives (EMDs) have been used in periodontal
      regenerative procedures, resulting in improvement of clinical parameters. Thus,
      the aim of this histomorphometric study is to evaluate the healing of periodontal
      defects after treatment with EMD under the influence of DM. METHODS: Twenty
      Wistar rats were randomly assigned to two groups: group 1 (G1): DM was induced
      with a single intraperitoneal injection of streptozotocin (STZ) (n = 10); group 2
      (G2): rats were not exposed to STZ (n = 10). Seven days after DM induction,
      bilateral fenestration defects were created at the buccal aspect of the first
      mandibular molar. After the surgeries, the defects of each animal were randomly
      assigned to two subgroups: non-treated (control) and treated with EMD. The
      animals were euthanized 21 days later, and the percentage of defect fill (DF),
      newly formed bone density (BD), and new cementum formation (NCF) were
      histometrically assessed. The number of osteoclasts was determined by tartrate
      resistant acid phosphatase. Weight and blood glucose were also analyzed. Mann
      Whitney U test was used for comparison among groups and Wilcoxon test for
      comparison between the start and end times (weight and blood glucose) and between
      treatments (NCF and number of osteoclasts). One-way analysis of variance was used
      to assess DF and BD. Tukey test was used when the analysis of variance test
      detected significant differences (alpha = 5%). RESULTS: G1 (DM) showed less DF
      and BD compared with G2. EMD provided an increased DF in both groups and enhanced
      BD and NCF only in G2. The number of TRAP-positive osteoclasts was significantly
      higher in EMD-treated sites of G1. CONCLUSIONS: DM may produce a significant
      detrimental effect on BD. EMD may provide greater DF under diabetic or normal
      conditions; however, it may not significantly increase NCF in animals with DM.

PMID- 23121458
TI  - Are periodontal bacterial profiles and placental inflammatory infiltrate in
      pregnancy related to birth outcomes?
AB  - BACKGROUND: The aim of this study is to determine whether periodontal clinical
      parameters, periodontal bacterial profiles, and inflammatory infiltrate in
      placental chorionic villi are associated with adverse pregnancy results. METHODS:
      The authors designed an observational case-control study in 244 postpartum
      females: mothers with preterm/low-birth weight newborns (n = 91 cases) and
      mothers with full-term, normal-weight infants (n = 153 controls).
      Sociodemographic, gynecologic, and periodontal variables were gathered for all
      participants. Data on placental inflammatory infiltrate in biopsies from 68 cases
      and 65 controls and the gingival bacterial profile in mothers with periodontitis
      were gathered, detecting associations with bivariate analyses and constructing a
      multiple logistic regression model with the number of positive inflammatory cells
      as the dependent variable. RESULTS: Periodontal values were significantly worse
      in cases versus controls. Numbers of leukocyte subsets per square millimeters in
      maternal and fetal vascular spaces were similar between cases and controls. CD45
      in maternal placental space was related to the presence of periodontitis (P =
      0.029) but not to case or control group (P = 0.264). The anaerobic and commensal
      bacterial profile in mothers with periodontitis was similar between the groups.
      CONCLUSIONS: Periodontal disease was more severe and a periodontitis diagnosis
      more frequent in mothers with preterm or low-birth weight versus normal delivery.
      No differences in anaerobic or commensal bacterial profile were found between
      mothers with periodontitis in the two groups. Local placental factors, such as
      the nature of the inflammatory infiltrate and slightly higher expression of
      cyclooxygenase-2 in the females with these adverse pregnancy outcomes, may be
      related to a subclinical proinflammatory status that could contribute to
      triggering premature labor.

PMID- 23121459
TI  - Thermo-reversible green tea catechin gel for local application in chronic
      periodontitis: a 4-week clinical trial.
AB  - BACKGROUND: Green tea extract is a naturally occurring antimicrobial agent,
      consisting of polyphenols (catechin) with anticariogenic, anti-inflammatory,
      anticollagenolytic properties. Hence, in the present study, an attempt was made
      to develop a thermo-reversible sustained-release green tea gel and to study its
      clinical effects on patients with chronic periodontitis (CP). METHODS: Thermo
      reversible sustained-release green tea catechin gel was prepared and tested for
      its in vitro release characteristics. An in vivo controlled, randomized, split
      mouth single-evaluator masked study was conducted. Thirty patients with two sites
      in the contralateral quadrants having probing depths (PDs) of >=4 mm were
      selected. Assessment of gingival index (GI), PD, and relative clinical attachment
      levels (rCALs) was done at baseline and at 4 weeks. Green tea and placebo gels
      were placed at test and control sites as an adjunct to Phase 1 periodontal
      therapy. RESULTS: Comparison of the mean +/- SD GI, PD, and rCAL values within
      the test group at baseline (1.92 +/- 0.24, 4.93 +/- 0.58, and 9.97 +/- 0.72,
      respectively) and the end of 4 weeks (0.01 +/- 0.04, 2.87 +/- 0.51, and 7.87 +/-
      0.51, respectively) showed high statistical significance (P <0.001). Comparison
      of mean +/- SD of GI, PD, and rCAL within the control group at baseline (1.95 +/-
      0.16, 4.77 +/- 0.50, and 9.73 +/- 0.45, respectively) and the end of 4 weeks
      (0.16 +/- 0.11, 3.8 +/- 0.48, and 8.76 +/- 0.43, respectively) showed
      significance with P <0.001. High significance was observed between the delta of
      measurements (0 to 4 weeks) of GI, PD, and rCAL between test (1.91 +/- 0.20, 2.06
      +/- 0.07, and 2.1 +/- 0.21, respectively) and control (1.79 +/- 0.05, 0.97 +/-
      0.02, and 0.97 +/- 0.02, respectively) groups. CONCLUSION: Adjunctive local drug
      therapy with thermo-reversible green tea gel has shown to reduce pockets and
      inflammation during the 4 weeks of the clinical trial in patients with CP.

PMID- 23121460
TI  - Boric acid irrigation as an adjunct to mechanical periodontal therapy in patients
      with chronic periodontitis: a randomized clinical trial.
AB  - BACKGROUND: The purpose of this single-masked, randomized, controlled clinical
      trial was to evaluate the effects of boric acid irrigation as an adjunct to
      scaling and root planing (SRP) on clinical and microbiologic parameters and
      compare this method with chlorhexidine irrigation and SRP alone in patients with
      chronic periodontitis (CP). METHODS: Forty-five systemically healthy patients
      with CP are included in this study. They were divided into three groups: 1) SRP +
      saline irrigation (C); 2) SRP + chlorhexidine irrigation (CHX); and 3) SRP +
      boric acid irrigation (B). To determine an ideal concentration of boric acid, a
      preclinical analysis was conducted. At baseline, 1 month, and 3 months after
      treatment, clinical measurements, including plaque index (PI), gingival index
      (GI), probing depth (PD), clinical attachment level (CAL), and bleeding on
      probing (BOP), were performed, and subgingival plaque samples were taken.
      Quantitative analysis of Porphyromonas gingivalis (Pg), Tannerella forsythia
      (Tf), and Treponema denticola (Td) was performed using real-time polymerase chain
      reaction (PCR) procedures. RESULTS: The concentration of boric acid is 0.75% in
      this study. All clinical parameters showed statistically significant reduction at
      all time points compared to baseline in all groups (P <0.001). Whole-mouth PD and
      CAL reduction was similar in all groups at all time points after treatment (P
      >0.05). The PD and CAL reductions for moderately deep pockets (PD >=5 and <7)
      were greater in the B group compared to other groups between baseline and 1 month
      (P <0.05). For deep pockets (PD >=7), reductions were similar in the B and CHX
      groups (P >0.05). BOP (percentage) was significantly lower in the B group
      compared with the CHX and C groups in the first month after treatment (P <0.001).
      GI and PI scores were significantly lower in the B and CHX groups compared with
      the C group at all time points after treatment (P <0.05). The amounts of Pg, Tf,
      and Td were significantly reduced in all treatment groups after 1 month (P
      <0.05). No statistically significant differences were detected among the groups
      for microbiologic parameters at any time points after treatment (P >0.05).
      CONCLUSIONS: The results of this study suggest that boric acid could be an
      alternative to chlorhexidine, and it might be more favorable because boric acid
      was superior in whole-mouth BOP as well as PD and CAL reduction for moderate
      pockets in early time periods.

PMID- 23121461
TI  - Re: "effect of the topical use of the antioxidant taurine on the two basement
      membrane proteins of regenerating oral gingival epithelium".

PMID- 23121462
TI  - Actinomyces bowdenii ulcerative keratitis in a dog.
AB  - A 5-year-old spayed female diabetic mixed-breed dog underwent phacoemulsification
      and intraocular lens implantation to correct bilateral hypermature cataracts. Two
      months postsurgery, the patient presented with ulcerative keratitis and
      multifocal stromal abscessation OD, which was controlled, but never resolved,
      with topical fluoroquinolone therapy. The patient re-presented 2 months later
      with a new, raised, white gritty corneal opacity associated with hyperemia,
      chemosis, and blepharospasm OD. Cytology of the right cornea revealed filamentous
      bacteria, suggestive of Actinomyces spp. Actinomyces bowdenii was subsequently
      isolated in pure culture and identified via 16s rDNA sequencing. Actinomyces
      bowdenii has never before been described as a cause of ocular infection. An
      immunosuppressed corneal environment likely contributed to this opportunistic
      Actinomycosis. The infection was not controlled with fluoroquinolone therapy, and
      the isolate, in vitro, was resistant to three fluoroquinolones (ciprofloxacin,
      ofloxacin, and levofloxacin), which also has not been previously reported for
      this species of Actinomyces. A superficial keratectomy with conjunctival graft
      was employed to successfully manage the infection. 

PMID- 23121463
TI  - Constructing a quantitative correlation between N-substituent sizes of chiral
      ligands and enantioselectivities in asymmetric addition reactions of diethylzinc
      with benzaldehyde.
AB  - Using the asymmetric addition reaction of diethylzinc with benzylaldehyde as a
      model, we have demonstrated that excellent correlations exist between steric
      reference parameters (Charton and Sterimol values) for appropriate sets of
      substituents present on chiral 1,2-amino-phosphoramide ligands and the
      enantiomeric ratios of alcohol products produced in this process.

PMID- 23121464
TI  - Dynamics and kinetics of structure formation in molecularly tethered
      fluorocarbon/hydrocarbon amphiphiles.
AB  - Biphasic fluorocarbon/hydrocarbon amphiphiles tethered to cores at distances
      commensurate with their packing requirement can provide thermodynamic pathways
      toward equilibrium. This contrasts with the analogous semifluorinated alkanes.
      The dynamics of a fluorous biphasic hexa(3,5-substituted-phenyl)benzene (HPB) is
      studied with dielectric spectroscopy as a function of temperature and pressure in
      comparison to the parent biphasic diphenylacetylene (DPA). Dielectric
      spectroscopy is a sensitive probe of the fluorocarbon environment through the end
      C-F dipole. Four dielectrically active processes were observed that associate
      with the CF(3) environment within the different phases (isotropic, liquid-like
      lamellar, solid lamellar, glassy state). Pressure facilitates the construction of
      the equilibrium phase diagram. The kinetic pathways to fluorocarbon organization
      are explored by pressure-jump experiments. A highly cooperative process was found
      that is atypical of a nucleation and growth process expected for first-order
      transitions.

PMID- 23121465
TI  - Molecular dynamics investigation on a series of HIV protease inhibitors:
      assessing the performance of MM-PBSA and MM-GBSA approaches.
AB  - The binding free energies (DeltaG(Bind)) obtained from molecular mechanics with
      Poisson-Boltzmann surface area (MM-PBSA) or molecular mechanics with Generalized
      Born surface area (MM-GBSA) calculations using molecular dynamics (MD)
      trajectories are the most popular procedures to measure the strength of
      interactions between a ligand and its receptor. Several attempts have been made
      to correlate the DeltaG(Bind) and experimental IC(50) values in order to observe
      the relationship between binding strength of a ligand (with its receptor) and its
      inhibitory activity. The duration of MD simulations seems very important for
      getting acceptable correlation. Here, we are presenting a systematic study to
      estimate the reasonable MD simulation time for acceptable correlation between
      DeltaG(Bind) and experimental IC(50) values. A comparison between MM-PBSA and MM
      GBSA approaches is also presented at various time scales. MD simulations (10 ns)
      for 14 HIV protease inhibitors have been carried out by using the Amber program.
      MM-PBSA/GBSA based DeltaG(Bind) have been calculated and correlated with
      experimental IC(50) values at different time scales (0-1 to 0-10 ns). This study
      clearly demonstrates that the MM-PBSA based DeltaG(Bind) (DeltaG(Bind)-PB) values
      provide very good correlation with experimental IC(50) values (quantitative and
      qualitative) when MD simulation is carried out for a longer time; however, MM
      GBSA based DeltaG(Bind) (DeltaG(Bind)-GB) values show acceptable correlation for
      shorter time of simulation also. The accuracy of DeltaG(Bind)-PB increases and
      DeltaG(Bind)-GB remains almost constant with the increasing time of simulation.

PMID- 23121467
TI  - The effectiveness of a health education intervention on self-care of traumatic
      wounds.
AB  - AIMS AND OBJECTIVES: To explore the effectiveness of wound care programme for
      emergency traumatic patient in Taiwan. BACKGROUND: Wound care is one of the most
      major issues for trauma patients at home. Wound infection has been alerted mostly
      on medical treatment. Little is known about how healthcare education impact
      patient care of traumatic wound after discharged from emergency department.
      DESIGN: A quasi-experimental design was used by using two groups post-test.
      METHODS: Random sampling was used to recruited participants, 89 participants in
      each group in emergency department at a medical centre in Taiwan. A 25-minute
      wound care programme was given to patients in the intervention group. A
      questionnaire was used to evaluate the effectiveness of the programme after 72
      hours as patient followed up in out-patient department. The data of wound
      infection were collected from patient's medical record by followed 2 weeks after
      injured. RESULTS: After wound care programme, the knowledge, skills of wounds
      care, the satisfaction of health education in experimental group are better than
      the control group (p < 0.05). Wound infection rate in experimental group (9%) is
      lower than control group (20.2%), and statistically significant (p < 0.05).
      CONCLUSION: The wound care programme could increase the knowledge, skills of
      wound care of emergency patient and reduce the wound infection rate. RELEVANCE TO
      CLINICAL PRACTICE: Wound care requites technical knowledge; thus, practical
      demonstration of teaching and self-practice is more effectiveness for patients in
      learning their wound care. An appropriated health programme can improve the
      patients' wound care and care quality.

PMID- 23121466
TI  - Different regions of the HPV-E7 and Ad-E1A viral oncoproteins bind competitively
      but through distinct mechanisms to the CH1 transactivation domain of p300.
AB  - p300 is a transcriptional coactivator that participates in many important
      processes in the cell, including proliferation, differentiation, and apoptosis.
      The viral oncoproteins, adenovirus (Ad) E1A and human papillomavirus (HPV) E7,
      have been implicated in binding to p300. The Ad-E1A-p300 interaction has been
      shown to result in the induction of cellular proliferation, epigenetic
      reprogramming, and cellular transformation and cancer. The HPV-E7-p300
      interaction, on the other hand, is not well understood. p300 contains three zinc
      binding domains, CH1-CH3, and studies have shown that Ad-E1A can bind to the p300
      CH1 and CH3 domains whereas E7 can bind to the CH1 domain and to a lesser extent
      to the CH2 and CH3 domains. Here we address how high-risk HPV16-E7 and Ad5-E1A,
      which have different structures, can both bind the p300 CH1 domain. Using pull
      down, gel filtration, and analytical ultracentrifugation studies, we show that
      the N-terminus and CR1 domains of Ad5-E1A and the CR1 and CR2 domains of HPV16-E7
      bind to the p300 CH1 domain competitively and with midnanomolar and low
      micromolar dissociation constants, respectively. We also show that Ad5-E1A can
      form a ternary complex with the p300 CH1 domain and the retinoblastoma pRb
      transcriptional repressor, whereas HPV16-E7 cannot. These studies suggest that
      the HPV16-E7 and Ad5-E1A viral oncoproteins bind to the same p300 CH1 domain to
      disrupt p300 function by distinct mechanisms.

PMID- 23121468
TI  - A single-item measure of social identification: reliability, validity, and
      utility.
AB  - This paper introduces a single-item social identification measure (SISI) that
      involves rating one's agreement with the statement 'I identify with my group (or
      category)' followed by a 7-point scale. Three studies provide evidence of the
      validity (convergent, divergent, and test-retest) of SISI with a broad range of
      social groups. Overall, the estimated reliability of SISI is good. To address the
      broader issue of single-item measure reliability, a meta-analysis of 16 widely
      used single-item measures is reported. The reliability of single-item scales
      ranges from low to reasonably high. Compared with this field, reliability of the
      SISI is high. In general, short measures struggle to achieve acceptable
      reliability because the constructs they assess are broad and heterogeneous. In
      the case of social identification, however, the construct appears to be
      sufficiently homogeneous to be adequately operationalized with a single item. 

PMID- 23121469
TI  - Unusual presentations of spider angiomas.

PMID- 23121470
TI  - The McGrath(r) Series 5 videolaryngoscope vs the Macintosh laryngoscope: a
      randomised, controlled trial in patients with a simulated difficult airway.
AB  - We compared the McGrath(r) Series 5 videolaryngoscope with the Macintosh
      laryngoscope in a simulated difficult airway, using manual in-line stabilisation
      in 88 anaesthestised patients of ASA physical status 1-2. The primary outcome was
      laryngoscopic view. Secondary outcomes included rates of successful tracheal
      intubation and complications. A Cormack and Lehane grade-1 or -2 view was found
      in all patients when using the McGrath compared with 45 (51%, p < 0.0001) using
      the Macintosh laryngoscopes. The mean (SD) percentage of glottic opening was 82
      (23)% using the McGrath compared with 13 (23)% using the Macintosh (p < 0.0001).
      In 66 out of 88 patients (75%), the McGrath improved the glottic view by one to
      three grades compared with the Macintosh (p < 0.001). Intubation of the trachea
      was successful in all patients using the McGrath, while the Macintosh was
      successful in 26 (59%, p < 0.001). There was no significant difference in the
      complication rates between the devices.

PMID- 23121471
TI  - Sleep in the unresponsive wakefulness syndrome and minimally conscious state.
AB  - The goal of our study was to investigate different aspects of sleep, namely the
      sleep-wake cycle and sleep stages, in the vegetative state/unresponsive
      wakefulness syndrome (VS/UWS), and minimally conscious state (MCS). A 24-h
      polysomnography was performed in 20 patients who were in a UWS (n=10) or in a MCS
      (n=10) because of brain injury. The data were first tested for the presence of a
      sleep-wake cycle, and the observed sleep patterns were compared with standard
      scoring criteria. Sleep spindles, slow wave sleep, and rapid eye movement sleep
      were quantified and their clinical value was investigated. According to our
      results, an electrophysiological sleep-wake cycle was identified in five MCS and
      three VS/UWS patients. Sleep stages did not always match the standard scoring
      criteria, which therefore needed to be adapted. Sleep spindles were present more
      in patients who clinically improved within 6 months. Slow wave sleep was present
      in eight MCS and three VS/UWS patients but never in the ischemic etiology. Rapid
      eye movement sleep, and therefore dreaming that is a form of consciousness, was
      present in all MCS and three VS/UWS patients. In conclusion, the presence of
      alternating periods of eyes-open/eyes-closed cycles does not necessarily imply
      preserved electrophysiological sleep architecture in the UWS and MCS, contrary to
      previous definition. The investigation of sleep is a little studied yet simple
      and informative way to evaluate the integrity of residual brain function in
      patients with disorders of consciousness with possible clinical diagnostic and
      prognostic implications.

PMID- 23121472
TI  - A subset of histamine receptor ligands improve thermotolerance of the yeast
      Saccharomyces cerevisiae.
AB  - AIMS: Histamine interacts with the stress response in eukaryotes. This study
      investigated the effects of antihistamines on the heat shock (HS) response in
      yeast, thereby exploring their functions in a well-established histamine receptor
      (H(x) R)-free model. METHODS AND RESULTS: Stress response was evaluated by
      determining growth and viability of postlogarithmic phase grown yeast cultures
      after HS at 53 degrees C for 30 min. The effects of H(x) R ligands were
      investigated following short- and long-term administration. The H(1) R antagonist
      dimethindene exerted dose-related antifungal actions, whereas the H(2) R
      antagonist ranitidine failed to elicit any effect. In contrast, the H(3/4) R and
      H(4) R ligands, thioperamide and JNJ7777120, respectively, induced the
      thermotolerant phenotype. The circumvention of thermotolerance by cycloheximide
      and the induction of Hsp70 and Hsp104 expression indicated the contribution of de
      novo protein synthesis in the adaptive process, likely directed towards
      alterations in Hsp expression. CONCLUSIONS: The data provide evidence for the
      differential function of H(x) R ligands in thermotolerance induction in yeast.
      SIGNIFICANCE AND IMPACT OF THE STUDY: First demonstration of the action of
      antihistamines in the HS response in yeast. The work supports the potential H(x)
      R-independent functions of histaminergic compounds in fungal adaptation and
      stimulates research on the prospect of their exploitation in eukaryotic
      (patho)physiology.

PMID- 23121474
TI  - Social identity and stroke: 'they don't make me feel like, there's something
      wrong with me'.
AB  - Over 85% of the people survive stroke; and of those, over 80% are discharged to
      the community. However, the majority do not recover completely. Loss of identity
      is a commonly reported experience after stroke. Studies focus on the individual
      survivors' use of their own cognitive resources to adapt to change, rather than
      examining the effects of social interactions on stroke survivors' identities.
      Social relationships are the foundation upon which survivors rebuild skills to
      engage with the world, yet little is known about the ways in which families,
      friends and neighbours provide a context for the recreation of a sense of self
      and activities after stroke. This article draws on situational analysis grounded
      theory analysis of in-depth individual interviews with nine middle-aged survivors
      of stroke. In situational analysis, the original grounded theory methods proposed
      by Glaser and Strauss are used; however, the situational context, and how
      environments and relationships influence actions, is explicitly analysed. Our
      objective was to understand the ways in which family, social, and community
      resources might enhance stroke survivors' participation in personally meaningful
      activities over the long term. The qualitative accounts of these survivors reveal
      how social support helped them maintain or more importantly regain a position in
      society. Following any life-changing event, people's sense of self is fluid. A
      relevant social position entitles stroke survivors to become actively involved in
      setting their own goals and maintaining a positive identity. However, as these
      participants attested, stroke impaired their social position and resources to
      reject an imposed social position. It was difficult for these survivors to
      construct a valued social identity without the support of other people. Future
      studies should explore the consequences of social interactions with others and
      how social attitudes about stroke disability affects individual's activity
      options, professional practice, and ultimately development of a positive
      poststroke identity. 

PMID- 23121473
TI  - Vildagliptin action on some adipocytokine levels in type 2 diabetic patients: a
      12-month, placebo-controlled study.
AB  - OBJECTIVE: To evaluate the action of vildagliptin + metformin on some
      adipocytokine levels, glycemic control, and beta-cell function in type 2 diabetic
      patients. RESEARCH DESIGN AND METHODS: A total of 171 patients with poor glycemic
      control were instructed to add after a 8 +/- 2 month-run-in period with
      metformin, vildagliptin 50 mg twice a day or placebo for 12 months. MAIN OUTCOME
      MEASURES: We evaluated at 3, 6, 9, and 12 months, the body mass index (BMI),
      glycemic control, fasting plasma insulin (FPI), homeostasis model assessment
      insulin resistance index (HOMA-IR), homeostasis model assessment beta-cell
      function index (HOMA-beta), fasting plasma proinsulin (FPr), proinsulin/fasting
      plasma insulin ratio (Pr/FPI ratio), C-peptide, glucagon, resistin, retinol
      binding protein-4 (RBP-4), chemerin, and tumor necrosis factor-alpha (TNF-alpha).
      Patients also underwent a combined euglycemic hyperinsulinemic and hyperglycemic
      clamp, with subsequent arginine stimulation to assess insulin sensitivity and
      insulin secretion. RESULTS: After 12 months of vildagliptin + metformin, we
      observed a better decrease of body weight, glycemic control, HOMA-IR, and
      glucagon, and a better increase of HOMA-beta, and of all the measures of beta
      cell function, compared to placebo + metformin. Vildagliptin + metformin also
      decreased resistin, RBP-4, and chemerin better. CONCLUSION: Vildagliptin seems to
      have a positive action on some adipocytokines related to inflammation.

PMID- 23121475
TI  - Effect of cluster set configurations on power clean technique.
AB  - The purpose of this investigation was to examine the effects of cluster set
      configurations on power clean technique. Ten male, recreational weightlifters
      performed three sets of six repetitions at 80% of one repetition max with 0 (P0),
      20 (P20) or 40 seconds (P40) inter-repetition rest. During the first and second
      set of P0, the catch and first pull were in a more forward position during
      repetition 6 as compared to repetition 1, respectively. During the second set of
      P40, differences in horizontal displacement were found between repetitions 1 and
      6 for the second pull and the loop. During the third set of P40, differences in
      horizontal displacement were found between repetitions 1 and 6 for the first
      pull, transition, and beginning of the second pull. No differences in horizontal
      displacement were found between repetitions 1 and 6 during P20. During each set
      of P0, vertical displacement decreased between repetitions 1 and 6 (1.02 +/- 0.07
      m vs. 0.94 +/- 0.06 m; Mean +/- s). Cluster set configurations led to the
      maintenance of vertical displacement throughout all sets. The results demonstrate
      cluster set configurations with greater than 20 seconds inter-repetition rest
      maintain weightlifting technique to a greater extent than a traditional set
      configuration.

PMID- 23121476
TI  - GPCR heterodimers: asymmetries in ligand binding and signalling output offer new
      targets for drug discovery.
AB  - Dimers of GPCRs have held the imagination of researchers for almost 20 years.
      However, only recently has their value as potentially novel drug targets been
      increased significantly, and primarily, in the context of GPCR heterodimers. The
      view of receptor heterodimers as allosteric machines has transformed the way we
      understand structural and functional asymmetries inherent in their organization.
      These asymmetries alter both signalling output and how they might be targeted
      pharmacologically. The paper in this issue of BJP by Siddiquee and colleagues ()
      highlights our growing understanding of such asymmetries and their implications.
      They show that heterodimers of the angiotensin II AT1 receptor and the apelin
      receptor recognize and respond to their respective ligands in distinct ways from
      the parent receptors expressed alone. Further, they demonstrate asymmetric
      allosteric effects in the context of the heterodimer that may have significant
      implications for our understanding of such receptor complexes. LINKED ARTICLE:
      This article is a commentary on the research paper by Siddiquee et al., pp. 1104
      1117 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476
      5381.2012.02192.x.

PMID- 23121477
TI  - Intramuscular architecture of the autochthonous back muscles in humans.
AB  - Many training concepts take muscle properties such as contraction speed or muscle
      topography into account to achieve an optimal training outcome. Thus far, the
      internal architecture of muscles has largely been neglected, although it is well
      known that parameters such as pennation angles or the lengths of fascicles but
      also the proportions of fleshy and tendinous fascicle parts have a major impact
      on the contraction behaviour of a muscle. Here, we present the most detailed
      description of the intramuscular fascicle architecture of the human perivertebral
      muscles available so far. For this, one adult male cadaver was studied. Our
      general approach was to digitize the geometry of each fascicle of the muscles of
      back proper (Erector spinae) - the Spinalis thoracis, Iliocostalis lumborum,
      Longissimus thoracis and the Multifidus thoracis et lumborum - and of the deep
      muscles of the abdomen - Psoas minor, Psoas major and Quadratus lumborum - during
      a layerwise dissection. Architectural parameters such as fascicle angles to the
      sagittal and the frontal planes as well as fascicle lengths were determined for
      each fascicle, and are discussed regarding their consequences for the function of
      the muscle. For example, compared with the other dorsovertebral muscles, the
      Longissimus thoracis can produce greater shortening distances because of its
      relatively long fleshy portions, and it can store more elastic energy due to both
      its relatively long fleshy and tendinous fascicle portions. The Quadratus
      lumborum was outstanding because of its many architectural subunits defined by
      distinct attachment sites and fascicle lengths. The presented database will
      improve biomechanical models of the human trunk by allowing the incorporation of
      anisotropic muscle properties such as the fascicle direction into finite element
      models. This information will help to increase our understanding of the
      functionality of the human back musculature, and may thereby improve future
      training concepts.

PMID- 23121478
TI  - Psychosocial factors influencing the recovery of athletes with anterior cruciate
      ligament injury: a systematic review.
AB  - This review describes the psychosocial factors that affect recovery following
      anterior cruciate ligament (ACL) injury and reconstructive surgery in athletes. A
      systematic search in literature with inclusion and exclusion criteria on PubMed,
      PsycINFO, and Embase was performed. Articles used in this review were divided in
      five different parts according to the biopsychosocial model of Wiese-Bjornstal,
      with the addition of intervention studies. The results showed that a high
      internal Health Locus of Control and a high self-efficacy were useful cognitive
      factors to facilitate the recovery. Athletes with a low level of fear of reinjury
      had the best knee outcome after the injury followed by a reconstruction. In
      addition, athletes who returned to sport had less fear of reinjury and were more
      experienced and established athletes compared with athletes who did not return to
      sport. Furthermore, researchers showed that there was a positive relation between
      goal setting and adherence, which in turn yielded a positive relation with the
      outcome of the rehabilitation of an ACL injury. There were several psychosocial
      interventions that appeared to be facilitating the rehabilitation process. 

PMID- 23121479
TI  - Psychological modulation in patients surgically intervened for gastroesophageal
      reflux disease.
AB  - Gastroesophageal reflux disease (GERD) has been related with certain
      psychological dimensions. The influence of mood, emotional intelligence, and
      perceived quality of life on clinical symptoms and outcome of antireflux surgery
      was evaluated in GERD patients with and without hiatal hernia. The study included
      61 patients who were diagnosed with GERD between 2003 and 2008: 16 of them
      without hiatal hernia (group A) and 45 of them with hiatal hernia (group B). All
      of these patients had undergone laparoscopic antireflux surgery. Patients were
      clinically examined and evaluated with the following instruments: Short Form (SF)
      36 Health Survey, Gastrointestinal Quality of Life Index, Hospital Anxiety and
      Depression (HAD) Scale, and Trait Meta-Mood Scale (TMMS)-24. Proportions were
      compared by using the chi-squared test; averages were compared by using the
      Student's t-test (with Bonferroni's correction). In general, our patients
      intervened for GERD showed results lower than normal or close to the lower limit
      of normal in the administered tests. Patients in the group without hernia were
      younger (P < 0.001) and with lower American Society of Anaesthesiologists risk.
      They showed higher scores in the SF-36 dimensions: Physical Functioning, Physical
      Role and Emotional Role, and lower scores in the Social Role (P < 0.001). They
      showed lower scores in the Emotional dimension of Gastrointestinal Quality of
      Life Index (P = 0.0068) and worse results in the Hospital Anxiety and Depression
      subscales of Anxiety (P < 0.001) and Depression (not significant). Men in the
      group without hernia showed higher scores than men in the group with hernia in
      the TMMS subscales corresponding to Emotional Clarity and Emotional Repair (P <
      0.001). Women in the group with hernia showed higher scores than women in the
      group without hernia regarding Emotional Clarity (P = 0.0012). GERD patients
      showed poor results in all the tests, and patients without hiatal hernia compared
      with patients with hernia showed higher levels of anxiety, which interfered with
      their social life. Moreover, they showed lower tolerance to stress and higher
      frustration, fear, and worry. On the basis of such unfavorable phychoemotional
      results observed with GERD patients (especially those without hernia) in the
      different tests, we propose that improving our knowledge of the psychological
      profile of GERD patients - particularly those without hiatal hernia - could help
      in designing individualized medical and psychological therapies and increase
      success rates. 

PMID- 23121480
TI  - May serum levels of advanced oxidized protein products serve as a prognostic
      marker of disease duration in patients with idiopathic Parkinson's disease?
AB  - Protein and amine halogenation is a type of oxidative stress induced by
      phagocytic overstimulation, and its role in Parkinson's disease (PD) has not been
      discerned. We have detected that advanced oxidized protein products, markers of
      protein halogenation, are reliably enhanced in serum of patients with PD (n=60)
      relative to control subjects (n=45, p<0.012), and to a lesser extent in the
      cerebrospinal fluid. Amine halogenation, as evaluated through 3-chlorotyrosine,
      is not affected. Mieloperoxidase and hydrogen peroxide levels, halogenative
      factors of phagocytes, are devoid of changes. Levels of advanced oxidized protein
      products are progressively reduced over time, and the duration of PD is larger in
      the Hoehn-Yahr-stage-2/3 patients (n=34) with low serum levels (R(2)=0.0145,
      p<0.003). Levodopa treatment contributes to this reduction (R(2)=0.259, p<0.001).
      These protein products are not cytotoxic, unlike 3-chlorotyrosine, but they are
      known to form inflammatory mediators after conjugation with serum albumin. Our
      observations lead to the hypothesis that the serum level of advanced oxidized
      protein products is a prognostic marker of PD duration, and these oxidized
      proteins could participate in the development of parkinsonian neurodegeneration.

PMID- 23121481
TI  - Body maps do not facilitate older children's report of touch.
AB  - In a single experiment, we assessed the effect of body maps on reports of touch
      by 5- and 6-year-olds, 9- and 10-year-olds, and adults. Children and adults
      participated in a staged event in which they were touched four times. Immediately
      following the event, children and adults were asked to either show using a body
      map or show using their own body where they had been touched. Consistent with
      prior research, body maps were ineffective with 5- and 6-year-olds. Furthermore,
      although older children and adults reported more touches and were more accurate
      than younger children, body maps did not enhance the quality of their reports. We
      conclude that the provision of a body map does not facilitate reports of touch by
      any age group, raising serious questions about their use in forensic contexts.

PMID- 23121485
TI  - Highly efficient extraction of cellular nucleic acid associated proteins in vitro
      with magnetic oxidized carbon nanotubes.
AB  - Nucleic acid associated proteins (NAaP) play the essential roles in gene
      regulation and protein expression. The global analysis of cellular NAaP would
      give a broad insight to understand the interaction between nucleic acids and the
      associated proteins, such as the important proteinous regulation factors on
      nucleic acids. Proteomic analysis presents a novel strategy to investigate a
      group of proteins. However, the large scale analysis of NAaP is yet impossible
      due to the lack of approaches to harvest target protein groups with a high
      efficiency. Herein, a simple and efficient method was developed to collect
      cellular NAaP using magnetic oxidized carbon nanotubes based on the strong
      interaction between carbon nanotubes and nucleic acids along with corresponding
      associated proteins. We found that the magnetic oxidized carbon nanotubes
      demonstrated a nearly 100% extraction efficiency for intracellular nucleic acids
      from cells in vitro. Importantly, the proteins associated on nucleic acids could
      be highly efficiently harvested using magnetic oxidized carbon nanotubes due to
      the binding of NAaP on nucleic acids. 1594 groups of nuclear NAaP and 2595 groups
      of cellular NAaP were extracted and identified from about 1,000,000 cells, and
      803 groups of NAaP were analyzed with only about 10,000 cells, showing a
      promising performance for the proteomic analysis of NAaP from minute cellular
      samples. This highly efficient extraction strategy for NAaP is a simple approach
      to identify cellular nucleic acid associated proteome, and we believed this
      strategy could be further applied in systems biology to understand the gene
      expression and regulation.

PMID- 23121486
TI  - Growth pathways in ultralow temperature Ge nucleation from Au.
AB  - Device integration on flexible or low-cost substrates has driven interest in the
      low-temperature growth of semiconductor nanostructures. Using in situ electron
      microscopy, we examine the Au-catalyzed growth of crystalline Ge at temperatures
      as low as 150  degrees C. For this materials system, the model for low
      temperature growth of nanowires, we find three distinct reaction pathways. The
      lowest temperature reactions are distinguished by the absence of any purely
      liquid state. From measurements of reaction rates and parameters such as
      supersaturation, we explain the sequence of pathways as arising from a kinetic
      competition between the imposed time scale for Ge addition and the inherent time
      scale for Ge nucleation. This enables an understanding of the conditions under
      which catalytic Ge growth can occur at very low temperatures, with implications
      for nanostructure formation on temperature-sensitive substrates.

PMID- 23121487
TI  - Determinants of HbA1c in nondiabetic Dutch adults: genetic loci and clinical and
      lifestyle parameters, and their interactions in the Lifelines Cohort Study.
AB  - OBJECTIVES: Glycated haemoglobin (HbA1c) is associated with cardiovascular
      disease risk in individuals without diabetes, and its use has been recommended
      for diagnosing diabetes. Therefore, it is important to gain further understanding
      of the determinants of HbA1c. The aim of this study was to investigate the
      effects of genetic loci and clinical and lifestyle parameters, and their
      interactions, on HbA1c in nondiabetic adults. DESIGN: Population-based cohort
      study. SETTING: Three northern provinces of the Netherlands. SUBJECTS: A total of
      2921 nondiabetic adults participating in the population-based LifeLines Cohort
      Study. MEASUREMENTS: Body mass index (BMI), waist circumference, HbA1c, fasting
      plasma glucose (FPG) and erythrocyte indices were measured. Data on current
      smoking and alcohol consumption were collected through questionnaires. Genome
      wide genotyping was performed, and 12 previously identified single-nucleotide
      polymorphisms (SNPs) were selected for replication and categorized as 'glycaemic'
      and 'nonglycaemic' SNPs according to their presumed mechanism(s) of action on
      HbA1c. Genetic risk scores (GRSs) were calculated as the sum of the weighted
      effect of HbA1c-increasing alleles. RESULTS: Age, gender, BMI, FPG, mean
      corpuscular haemoglobin, mean corpuscular haemoglobin concentration, current
      smoking and alcohol consumption were independent predictors of HbA1c, together
      explaining 26.2% of the variance in HbA1c, with FPG contributing 10.9%. We
      replicated three of the previously identified SNPs and the GRSs were also found
      to be independently associated with HbA1c. We found a smaller effect of the
      'nonglycaemic GRS' in females compared with males and an attenuation of the
      effect of the GRS of all 12 SNPs with increasing BMI. CONCLUSIONS: Our results
      suggest that a substantial portion of HbA1c is determined by nonglycaemic
      factors. This should be taken into account when considering the use of HbA1c as a
      diagnostic test for diabetes.

PMID- 23121489
TI  - Delirium in older patients: a diagnostic study of NEECHAM Confusion Scale in
      surgical intensive care unit.
AB  - AIMS AND OBJECTIVES: To estimate the diagnostic value and determine the
      feasibility of the NEECHAM Confusion Scale on critically ill older patients.
      BACKGROUND: Delirium is a common syndrome in hospitalised older patients,
      especially in surgical intensive care units, and the consequences of under
      detection can be very serious for older people. Therefore, assessment of the
      cognitive status of older patients using a valid instrument is important in
      intensive care units. DESIGN: A descriptive prospective design was used. METHODS:
      Consecutive nonintubated patients aged 65 and older, admitted to a surgical
      intensive care unit of an Italian hospital during a seven months period, were
      assessed for delirium using the NEECHAM scale and the Confusion Assessment Method
      for intensive care unit, once per shift, for 48 hours after admission. Cohen's
      kappa coefficient, ROC curve, sensitivity and specificity were estimated. An open
      ended questionnaire was used to assess user-friendliness of the scale. RESULTS: A
      sample of 41 older patients with a mean age of 78.3 years was studied. The kappa
      coefficient was 0.95. The sensitivity was 99.19%, specificity 95% at cut-off of
      25, and the area under the curve was 0.99 (CI 0.99-1.00). Nurses evaluated
      positively the scale as they were able to collect data during care process in
      maximum 10 minutes, but experienced problems in rating the appearance behaviour
      and physiological control items of the scale. CONCLUSIONS: Findings from this
      study confirm the good diagnostic value and ease of application of the NEECHAM
      scale with nonventilated intensive care patients. RELEVANCE TO CLINICAL PRACTICE:
      The NEECHAM scale can be used to detect delirium during the routine nursing
      assessment of nonintubated older patients as it requires minimal demand and
      stress on the patient as well as on the bedside nurse.

PMID- 23121488
TI  - Mn(2+)-nucleotide coordination at the myosin active site as detected by pulsed
      electron paramagnetic resonance.
AB  - Pulsed electron paramagnetic resonance at the microwave K(a) band (~30 GHz) was
      used to study the coordination of adenosine nucleotides to Mn(2+) at the active
      site of myosin ATPase and in solution. We have found that the electron spin echo
      (ESE) field sweep, electron-nuclear double resonance (ENDOR) and ESE envelope
      modulation (ESEEM) techniques are not sufficiently specific for reliable
      differentiation between the solvated and myosin-bound Mn.nucleotide complexes.
      Therefore, to directly detect binding of the Mn.nucleotide to myosin, we used
      nonhydrolizable nucleotide analogs, site-directed spin labeling, and pulsed
      electron-electron double resonance to detect spin probe-manganese dipolar
      interaction. We found that under substoichiometric conditions, both Mn.AMPPNP and
      Mn.ADP.AlF(4) form a complex with myosin, and Mn.ADP does not form such a
      complex. This correlates well with the biological dissociation of Mg.ADP from
      myosin after the hydrolysis of ATP. The analysis of (31)P ENDOR spectra reveals
      that in Mn.AMPPNP, Mn.ATP, and Mn.ADP at myosin or in solution, the nucleotide is
      coordinated to Mn(2+) by two phosphate groups, whereas in Mn.ADP.AlF(4), only one
      phosphate group is coordinated. The observation of two phosphates and one
      nitrogen in the coordination sphere of Mn.ADP in solution by ESEEM spectroscopy
      suggests that a significant population of Mn ions is coordinated by two ADP
      molecules, one of which is coordinated by phosphates, and the other one, by a
      nitrogen atom. The developed approach will be generally useful for monitoring the
      metal-protein binding when such binding does not provide reliable spectroscopic
      signatures.

PMID- 23121490
TI  - Cdx1 interacts physically with a subset of Hox proteins.
AB  - Cdx and Hox gene families encode homeodomain-containing transcription factors
      involved in anterior-posterior vertebral patterning. Although Cdx proteins are
      direct transcriptional regulators of Hox gene expression, both Hox and Cdx
      proteins are known to interact with other homeodomain transcription factors,
      leading us to speculate that Cdx and Hox proteins may also interact physically.
      In testing this, we found that that Cdx1 is indeed capable of associating with a
      subset of Hox proteins. This interaction is localized to the homeodomain region
      of both classes of proteins, is reliant on specific arginine residues in helix I
      of the Hox homeodomain, and is further modulated by N-terminal Hox sequences.
      More promiscuous interactions were seen with Hox proteins expressed in vivo,
      suggestive of bridging factors or post-translational modifications. Finally, we
      demonstrate that this interaction modulates Cdx-Hox transcriptional activity on a
      Hox-responsive element. This study is the first example of Cdx-Hox protein
      interactions and suggests that such complexes may modulate Hox and/or Cdx
      function.

PMID- 23121491
TI  - Emerging shale gas revolution in China.

PMID- 23121493
TI  - Conjunctival squamous cell carcinoma in a reindeer (Rangifer tarandus tarandus).
AB  - An 8-year-old female adult reindeer (Rangifer tarandus tarandus) was referred to
      the Veterinary Hospital of Madrid for evaluation of a conjunctival mass on the
      left eye which had been present for about 2 months. A surgical excision was
      performed and biopsy material submitted for light microscopic evaluation which
      confirmed the diagnosis of conjuctival squamous cell carcinoma. Nuclear p53
      immunolabeling was found in 52% of the neoplastic cells. Follow-up examination at
      12 months postsurgery did not reveal recurrence of this neoplasm. Conjunctival
      squamous cell carcinoma has not been reported previously in reindeer and seems to
      have similar characteristics to the one existing in bovine species. 

PMID- 23121492
TI  - Droplet microfluidics platform for highly sensitive and quantitative detection of
      malaria-causing Plasmodium parasites based on enzyme activity measurement.
AB  - We present an attractive new system for the specific and sensitive detection of
      the malaria-causing Plasmodium parasites. The system relies on isothermal
      conversion of single DNA cleavage-ligation events catalyzed specifically by the
      Plasmodium enzyme topoisomerase I to micrometer-sized products detectable at the
      single-molecule level. Combined with a droplet microfluidics lab-on-a-chip
      platform, this design allowed for sensitive, specific, and quantitative detection
      of all human-malaria-causing Plasmodium species in single drops of unprocessed
      blood with a detection limit of less than one parasite/MUL. Moreover, the setup
      allowed for detection of Plasmodium parasites in noninvasive saliva samples from
      infected patients. During recent years malaria transmission has declined
      worldwide, and with this the number of patients with low-parasite density has
      increased. Consequently, the need for accurate detection of even a few parasites
      is becoming increasingly important for the continued combat against the disease.
      We believe that the presented droplet microfluidics platform, which has a high
      potential for adaptation to point-of-care setups suitable for low-resource
      settings, may contribute significantly to meet this demand. Moreover, potential
      future adaptation of the presented setup for the detection of other
      microorganisms may form the basis for the development of a more generic platform
      for diagnosis, fresh water or food quality control, or other purposes within
      applied or basic science.

PMID- 23121494
TI  - Stereospecific transformation of protected P-H group into P-O or P-N group in one
      pot reaction.
AB  - A general and efficient procedure for converting 1,1-diethoxyalkylphosphinates
      into phosphonates or phosphonamides is described by the application of bromine
      with moderate to high yields and good purity in a one-pot reaction. H-Phosphinate
      reacts stereospecifically with bromine and subsequently couples with nucleophile
      to form the corresponding optically active R(1)P(O)(OEt)X with retention of
      configuration at the phosphorus center. For alpha-amino-H-phosphinates, the
      transformation could be realized without the protection of the amino group.

PMID- 23121495
TI  - Current assessment of docking into GPCR crystal structures and homology models:
      successes, challenges, and guidelines.
AB  - The growing availability of novel structures for several G protein-coupled
      receptors (GPCRs) has provided new opportunities for structure-based drug design
      of ligands against this important class of targets. Here, we report a systematic
      analysis of the accuracy of docking small molecules into GPCR structures and
      homology models using both rigid receptor (Glide SP and Glide XP) and flexible
      receptor (Induced Fit Docking; IFD) methods. The ability to dock ligands into
      different structures of the same target (cross-docking) is evaluated for both
      agonist and inverse agonist structures of the A2A receptor and the beta1- and
      beta2-adrenergic receptors. In addition, we have produced homology models for the
      beta1-adrenergic, beta2-adrenergic, D3 dopamine, H1 histamine, M2 muscarine, M3
      muscarine, A2A adenosine, S1P1, kappa-opioid, and C-X-C chemokine 4 receptors
      using multiple templates and investigated the ability of docking to predict the
      binding mode of ligands in these models. Clear correlations are observed between
      the docking accuracy and the similarity of the sequence of interest to the
      template, suggesting regimes in which docking can correctly identify ligand
      binding modes.

PMID- 23121496
TI  - The effects of autonomous and controlled regulation of performance-approach goals
      on well-being: a process model.
AB  - The main purpose of the present research was to propose and test a motivational
      model linking achievement goal approach and self-determination theory. First, the
      effects of performance-approach goals and the autonomous and controlling reasons
      underlying their pursuit on well-being were investigated. Second, the mediating
      variables (i.e., effort, goal attainment, need satisfaction, and thwarting) at
      play in these relationships were examined based on the self-concordance model
      (Sheldon & Elliot, 1999). The model was tested in two studies in educational and
      work settings using cross sectional (Study 1) and prospective designs (Study 2).
      The present results revealed that considering autonomous and controlled
      regulations underlying performance-approach goals predicted well-being above and
      beyond the strength of performance-approach goals. Moreover, the mediational
      sequence based on the self-concordance model was supported in both studies.
      Theoretical implications and directions for future research are discussed. 

PMID- 23121497
TI  - Male infertility: a critical review of pharmacologic management.
AB  - INTRODUCTION: Male factor infertility contributes partially and solely to the
      problem of childlessness in around 50% of the cases. Unfortunately, 30 - 50% of
      the etiologies of male infertility are unknown and therefore, no specific therapy
      can be instituted. Evidence-based medical therapy for male infertility is an
      attractive research area where a large number of clinical trials, controlled and
      uncontrolled, using different types of medications have been conducted yielding
      variable results and outcomes. AREAS COVERED: In this review, we summarize and
      evaluate the most important and most recent information pertaining to the use of
      different medications in male infertility and assign level of evidence to these
      medications. An extensive literature search was performed using the search
      engines: Pubmed, Science-direct, Ovid and Scopus. EXPERT OPINION: Male
      infertility represents a very challenging area of clinical medicine. Many
      different types of medications have been tried and very few have had satisfactory
      results. There is a huge need to advance and develop andrologic diagnostic
      techniques, focusing on the metabolomics and proteomics of the sperm, seminal
      plasma, and testicular tissue. Clarification of the causes of idiopathic male
      infertility and the discovery of novel molecular targets will help guide future
      innovative development of new pharmacologic agents.

PMID- 23121498
TI  - A comparison of clinical practice guidelines for proximal femoral fracture.
AB  - Clinical practice guidelines are designed to assist clinical decision-making by
      summarising evidence and forming recommendations. The number of available
      guidelines is vast and they vary in relevance and quality. We reviewed guidelines
      relevant to the management of a patient with a fractured neck of femur and
      explored similarities and conflicts between recommendations. As guidelines are
      often produced in response to an area of clinical uncertainty, recommendations
      differ. This can result in a situation where the management of a particular
      clinical problem will depend upon which guideline is followed. We explore the
      reasons for such differences.

PMID- 23121499
TI  - Pituitary function and functional outcome in adults after severe traumatic brain
      injury: the long-term perspective.
AB  - Post-traumatic hypopituitarism (PTHP) has been linked to disability and decreased
      quality of life. However, no studies have addressed the long-term consequences of
      PTHP in adults with severe traumatic brain injury (TBI) only. In this study, we
      evaluated the relationship between pituitary function, quality of life, and
      functioning in 51 patients (16-65 years of age) with severe TBI who were admitted
      to Sahlgrenska University Hospital, Gothenburg from 1999 to 2002. The patients
      were assessed once, 2-10 years after trauma. Data from the time of injury were
      collected retrospectively to adjust for injury severity. Outcome measures
      included hormonal testing, the Short Form-36 Health Survey, the Glasgow outcome
      scale-extended, and a self-report questionnaire specifically designed for this
      study and based on the International Classification of Functioning, Disability
      and Health. Of 51 patients, 14 (27.5%) presented with PTHP, and 11 (21.6%) had
      isolated growth hormone deficiency. Patients with PTHP were more often overweight
      at follow-up (p=0.01); the higher body mass index was partially explained by PTHP
      (R2 change=0.07, p=0.001). Otherwise no significant correlation was found among
      PTHP, functioning, or patient-reported quality of life. This study-which is
      unique in the homogeneity of the patients, the long follow-up time, and the use
      of injury severity as an outcome predictor-did not confirm results from previous
      studies linking PTHP to a worse outcome. Therefore, screening for PTHP might be
      restricted to specific subgroups such as overweight patients, indicating growth
      hormone deficiency.

PMID- 23121500
TI  - Development of a groEL gene-based species-specific multiplex polymerase chain
      reaction assay for simultaneous detection of Vibrio cholerae, Vibrio
      parahaemolyticus and Vibrio vulnificus.
AB  - AIMS: To develop an effective multiplex polymerase chain reaction (PCR) for the
      simultaneous detection of three important Vibrio species, Vibrio cholerae (Vc),
      V. parahaemolyticus (Vp) and V. vulnificus (Vv) using the groEL gene, a potential
      phylogenetic marker. METHODS AND RESULTS: Three species-specific primer sets were
      designed to target Vc, Vp and Vv. A total of 131 Vibrio and non-Vibrio strains
      were used to determine the specificity and sensitivity of primers. The primers
      produced specific PCR fragments from all target species strains and did not cross
      react with other Vibrio and non-Vibrio species. This PCR method showed good
      efficiency in detecting coexisting target species in the same sample with a
      detection limit of 100 pg of Vc, Vp and Vv from mixed purified DNA. Detection of
      three target species was also possible from artificially inoculated shellfish,
      flounder and sea water. CONCLUSIONS: The groEL gene is a potential marker for
      accurate simultaneous detection of Vc, Vp and Vv and could be used to detect
      these species in environmental and clinical samples. SIGNIFICANCE AND IMPACT OF
      THE STUDY: This newly developed multiplex PCR is a useful and cost-effective
      method that is applicable in a disease-outbreak prediction system and may provide
      an effective tool for both the epidemiologist and ecologist.

PMID- 23121501
TI  - Risk factors for QT interval prolongation owing to acute gastrointestinal
      haemorrhage in patients with cirrhosis.

PMID- 23121502
TI  - Development of an accelerometer-based multivariate model to predict free-living
      energy expenditure in a large military cohort.
AB  - This study developed a multivariate model to predict free-living energy
      expenditure (EE) in independent military cohorts. Two hundred and eighty-eight
      individuals (20.6 +/- 3.9 years, 67.9 +/- 12.0 kg, 1.71 +/- 0.10 m) from 10
      cohorts wore accelerometers during observation periods of 7 or 10 days.
      Accelerometer counts (PAC) were recorded at 1-minute epochs. Total energy
      expenditure (TEE) and physical activity energy expenditure (PAEE) were derived
      using the doubly labelled water technique. Data were reduced to n = 155 based on
      wear-time. Associations between PAC and EE were assessed using allometric
      modelling. Models were derived using multiple log-linear regression analysis and
      gender differences assessed using analysis of covariance. In all models PAC,
      height and body mass were related to TEE (P < 0.01). For models predicting TEE (r
      (2) = 0.65, SE = 462 kcal . d(-1) (13.0%)), PAC explained 4% of the variance. For
      models predicting PAEE (r (2) = 0.41, SE = 490 kcal . d(-1) (32.0%)), PAC
      accounted for 6% of the variance. Accelerometry increases the accuracy of EE
      estimation in military populations. However, the unique nature of military life
      means accurate prediction of individual free-living EE is highly dependent on
      anthropometric measurements.

PMID- 23121503
TI  - Comparison of health-related quality of life between patients with chronic
      obstructive pulmonary disease and the general population.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with lower
      health-related quality of life (HRQOL). Previous research has focused primarily
      on HRQOL in these patients, whereas few studies have compared HRQOL between
      patients with COPD and the general population. AIM: The aim of this study was to
      evaluate differences in HRQOL between patients with COPD stage 2 to COPD stage 4
      waiting to begin an outpatient pulmonary rehabilitation (PR) programme and
      Norwegian individuals with and without other chronic conditions. METHODS: A
      comparative survey design was used in this study of 100 patients with COPD
      waiting to begin PR and 3594 individuals from the general population. The SF-36
      questionnaire was used to evaluate HRQOL. RESULTS: Compared with the healthy
      general population, COPD patients waiting to begin PR had lower scores on all SF
      36 components and on the physical and mental health summary components (p <
      0.001). Scores for physical function, physical role, general health, vitality,
      social function, emotional role and the physical health component differed
      markedly between patients and the general population. Patients with COPD stage 4
      had lower HRQOL than did the general population and those with COPD stage 2 and
      COPD stage 3. CONCLUSIONS: The burden of COPD significantly affects HRQOL in
      patients with COPD waiting to begin PR, and those with COPD stage 4 are most
      affected. Action should be taken to support especially those patients with COPD
      stage 4.

PMID- 23121504
TI  - Degree of tumor shrinkage following neoadjuvant chemoradiotherapy: a potential
      predictor for complete pathological response in esophageal cancer?
AB  - Neoadjuvant chemoradiotherapy (CRT) before surgery results in a pathological
      complete response (pCR) rate in about 1/3 of the patients, which is correlated
      with survival. It was hypothesized that volumetric tumor response to CRT would
      correlate with outcomes. Patients who completed trimodality therapy, where
      planning, pre-, and post-CRT computed tomography scans were available, and
      pathology was reviewed by a central pathologist, were eligible for analysis.
      Absolute and relative tumor volume change pretreatment and post-treatment were
      correlated with pCR, locoregional recurrence (LRR), disease-free survival, and
      overall survival. Fifty-six patients were analyzed. pCR was observed in 30% of
      patients. Median follow up was 20.3 (range 4-89) months. The 2- and 4-year
      overall survival was 61.3% (95% confidence interval [CI]: 45-74) and 25.0%
      (95%CI: 11-41); proportion disease free was 32.1% (95% CI: 19-46) and 20.6% (9
      36) at 2 and 4 years, respectively. The median relative volume reduction was 17%
      (95% CI: -24, -3%). Using 20% as the criteria, the proportion of patients with
      pCR of >=20% versus <20% was 13/25 (52%) versus 4/31 (13%) for those who did not
      (odds ratio 7.3; 95% CI: 2-27). The LRR at 2 and 4 years were 29.5% (95% CI: 16
      43) and 36.2% (95% CI: 23-50). The relative tumor reduction >=20% was
      significantly correlated with LRR (hazard ratio 0.24; 95% CI: 0.07-0.8; p 0.02)
      at 2 and 4 years, respectively. Relative tumor volume reduction following CRT is
      correlated with pCR and LRR. Further investigations are warranted to examine the
      effect of volume change, alone or in conjunction with other factors as potential
      predictors for pathological response. 

PMID- 23121505
TI  - Is oxidized thioredoxin a major trigger for cysteine oxidation? Clues from a
      redox proteomics approach.
AB  - Cysteine oxidation mediates oxidative stress toxicity and signaling. It has been
      long proposed that the thioredoxin (Trx) system, which consists of Trx and
      thioredoxin reductase (Trr), is not only involved in recycling classical Trx
      substrates, such as ribonucleotide reductase, but it also regulates general
      cytoplasmic thiol homeostasis. To investigate such a role, we have performed a
      proteome-wide analysis of cells expressing or not the two components of the Trx
      system. We have compared the reversibly oxidized thiol proteomes of wild-type
      Schizosaccharomyces pombe cells with mutants lacking Trx or Trr. Specific Trx
      substrates are reversibly-oxidized in both strain backgrounds; however, in the
      absence of Trr, Trx can weakly recycle its substrates at the expense of an
      alternative electron donor. A massive thiol oxidation occurs only in cells
      lacking Trr, with 30% of all cysteine-containing peptides being reversibly
      oxidized; this oxidized cysteine proteome depends on the presence of Trxs. Our
      observations lead to the hypothesis that, in the absence of its reductase, the
      natural electron donor Trx becomes a powerful oxidant and triggers general thiol
      oxidation.

PMID- 23121506
TI  - Characterization of the nutritive value of tropical legume grains as alternative
      ingredients for small-scale pork producers using in vitro enzymatic hydrolysis
      and fermentation.
AB  - In the tropic, the small-scale pork production is negatively influenced by the
      low availability of high protein ingredients. The study aimed to compare the
      protein and starch hydrolysis as well as fibre fermentation of five tropical
      legume grains (Canavalia brasiliensis, CB; Lablab purpureus, LP; Vigna
      unguiculata, white WVU; pink PVU and red RVU) and a control (extruded full-fat
      soybean (SB)), using an in vitro model that simulated digestion in the
      gastrointestinal tract of pigs. A sequential in vitro hydrolysis was carried out
      with pepsin (120 min) and pancreatin (240 min) to determine the degree of
      hydrolysis (DH) of protein and starch. The indigestible residue was fermented in
      vitro with pig faecal inoculum to compare the modelled kinetics of gas production
      over 72 h and the production of short-chain fatty acids (SCFA). After 360 min of
      pepsin-pancreatin hydrolysis, SB and WVU had the highest protein hydrolysis (76%
      and 66%) and PVU and WVU the highest starch hydrolysis (70% and 64%) (p < 0.01).
      The in vitro fermentation of the indigestible residue of WVU resulted in the
      highest (482 ml/g DM; p < 0.001) and CB the lowest (335 ml/g DM) gas production.
      These data were consistent with the SCFA production. Butyrate, propionate and
      total SCFA were higher (or tended) for RVU and WVU when compared with CB and SB
      (p = 0.015-0.085). In conclusion, the high DH of protein and starch as well as
      the high gas and SCFA production obtained with raw WVU makes it an interesting
      alternative to SB as a feedstuff for swine nutrition in the tropic. Other legume
      grains (LP and CB) cannot be used by pigs in their raw form. 

PMID- 23121508
TI  - 15-month-olds' transfer of learning between touch screen and real-world displays:
      language cues and cognitive loads.
AB  - Infants have difficulty transferring information between 2D and 3D sources. The
      current study extends Zack, Barr, Gerhardstein, Dickerson & Meltzoff's (2009)
      touch screen imitation task to examine whether the addition of specific language
      cues significantly facilitates 15-month-olds' transfer of learning between touch
      screens and real-world 3D objects. The addition of two kinds of linguistic cues
      (object label plus verb or nonsense name) did not elevate action imitation
      significantly above levels observed when such language cues were not used.
      Language cues hindered infants' performance in the 3D->2D direction of transfer,
      but only for the object label plus verb condition. The lack of a facilitative
      effect of language is discussed in terms of competing cognitive loads imposed by
      conjointly transferring information across dimensions and processing linguistic
      cues in an action imitation task at this age.

PMID- 23121507
TI  - Inhibition of endothelial cell Ca2+ entry and transient receptor potential
      channels by Sigma-1 receptor ligands.
AB  - BACKGROUND AND PURPOSE: The Sigma-1 receptor (Sig1R) impacts on calcium ion
      signalling and has a plethora of ligands. This study investigated Sig1R and its
      ligands in relation to endogenous calcium events of endothelial cells and
      transient receptor potential (TRP) channels. EXPERIMENTAL APPROACH: Intracellular
      calcium and patch clamp measurements were made from human saphenous vein
      endothelial cells and HEK 293 cells expressing exogenous human TRPC5, TRPM2 or
      TRPM3. Sig1R ligands were applied and short interfering RNA was used to deplete
      Sig1R. TRP channels tagged with fluorescent proteins were used for subcellular
      localization studies. KEY RESULTS: In endothelial cells, 10-100 MUM of the Sig1R
      antagonist BD1063 inhibited sustained but not transient calcium responses evoked
      by histamine. The Sig1R agonist 4-IBP and related antagonist BD1047 were also
      inhibitory. The Sig1R agonist SKF10047 had no effect. Sustained calcium entry
      evoked by VEGF or hydrogen peroxide was also inhibited by BD1063, BD1047 or 4
      IBP, but not SKF10047. 4-IBP, BD1047 and BD1063 inhibited TRPC5 or TRPM3, but not
      TRPM2. Inhibitory effects of BD1047 were rapid in onset and readily reversed on
      washout. SKF10047 inhibited TRPC5 but not TRPM3 or TRPM2. Depletion of Sig1R did
      not prevent the inhibitory actions of BD1063 or BD1047 and Sig1R did not co
      localize with TRPC5 or TRPM3. CONCLUSIONS AND IMPLICATIONS: The data suggest that
      two types of Sig1R ligand (BD1047/BD1063 and 4-IBP) are inhibitors of receptor-
      or chemically activated calcium entry channels, acting relatively directly and
      independently of the Sig1R. Chemical foundations for TRP channel inhibitors are
      suggested.

PMID- 23121513
TI  - Size exclusion chromatography with multi detection in combination with matrix
      assisted laser desorption ionization-time-of-flight mass spectrometry as a tool
      for unraveling the mechanism of the enzymatic polymerization of polysaccharides.
AB  - Determination of the size distributions of natural polysaccharides is a
      challenging task. More advantageous for characterization are well-defined
      synthetic (hyper)-branched polymers. In this study we concentrated on synthetic
      amylopectin analogues in order to obtain and compare all available data for
      different distributions and size dependence of molecular weights. Two groups of
      well-defined synthetic branched polysaccharides were synthesized via an in vitro
      enzyme-catalyzed reaction using the enzyme phosphorylase b from rabbit muscle and
      Deinococcus geothermalis glycogen branching enzyme. Synthetic polymers had a
      tunable degree of branching (2%-13% determined via (1)H NMR) and a tunable degree
      of polymerization (30-350 determined indirectly via UV spectrometry). The systems
      used for separation and characterization of branched polysaccharides were SEC
      DMSO/LiBr and multi detection (refractive index detector, viscosity detector, and
      multi angle light scattering detector) and SEC-water/0.02% NaN(3); and SEC-50 mM
      NaNO(3)/0.02% NaN(3) and multi detection. Additionally the side chain length
      distribution of enzymatically debranched polysaccharides was investigated by
      matrix-assisted laser desorption ionization-time-of-flight mass spectrometry
      (MALDI-TOF MS) analysis. With this combination of characterization techniques, we
      were able not only to characterize the amylopectin analogues but also to solve
      parts of the molecular mechanism of their enzymatic polymerization. Moreover our
      materials showed potential to be standards in the field of natural
      polysaccharides characterization.

PMID- 23121514
TI  - The spatial and temporal arrangement of the radial glial scaffold suggests a role
      in axon tract formation in the developing spinal cord.
AB  - Radial glial cells serve diverse roles during the development of the central
      nervous system (CNS). In the embryonic brain, they are recognised as guidance
      conduits for migrating neuroblasts and as multipotent stem cells, generating both
      neurons and glia. While their stem cell capacities in the developing spinal cord
      are as yet not fully clarified, they are classically seen as a population of
      astrocytes precursors, before gradually disappearing as the spinal cord matures.
      Although the origins and lineages of CNS radial glial cells are being more
      clearly understood, the relationships between radial glial cells and growing
      white matter (WM) tracts are largely unknown. Here, we provide an in-depth
      description of the distribution and organisation of radial glial cell processes
      during the peak periods of axonogenesis in the rat spinal cord. We show that
      radial glial cell distribution is highly ordered in the WM from E14 to E18, when
      the initial patterning of axon tracts is taking place. We report that the density
      of radial glial cell processes is tightly conserved throughout development in the
      dorsal, lateral and ventral WM funiculi along the rostrocaudal axis of the spinal
      cord. We provide evidence that from E16 the dorsal funiculi grow within and are
      segregated by fascicles of processes emanating from the dorsomedial septum. The
      density of radial glial cells declines with the maturation of axon tracts and
      coincides with the onset of the radial glial cell-astrocyte transformation. As
      such, we propose that radial glial cells act as structural scaffolds by
      compartmentalising and supporting WM patterning in the spinal cord during
      embryonic development.

PMID- 23121515
TI  - Screening for chronic comorbid diseases in people with HIV: the need for a
      strategic approach.
AB  - Among people living with HIV, the proportion of deaths attributed to chronic
      noninfectious comorbid diseases has increased over the past 15 years. This is
      partly a result of increased longevity in the era of highly active antiretroviral
      therapy (HAART), and also because HIV infection is related, causally or
      otherwise, to several chronic conditions. These comorbidities include conditions
      that are strongly associated with modifiable risk factors, such as cardiovascular
      disease (CVD), diabetes, and renal and bone diseases, and increasingly management
      guidelines for HIV recommend risk evaluation for these conditions. The uptake of
      these screening approaches is often limited by the resources required for their
      application, and hence the management of risk reduction in most HIV-infected
      populations falls below a reasonable standard. The situation is compounded by the
      fact that few risk calculators have been adjusted for specific use in HIV
      infection. There is substantial overlap of risk factors for the four common
      comorbid diseases listed above that are especially relevant in HIV infection, and
      this offers an opportunity to develop a simple screening approach that
      encompasses the key risk factors for lifestyle-related chronic disease in people
      with HIV infection. This would identify those patients who require more in-depth
      investigation, and facilitate a stepwise approach to targeted management. Such a
      tool could improve communication between patient and clinician. A significant
      proportion of people with HIV are sufficiently engaged with their care to
      participate in health promotion and take the lead in using patient-centric
      screening measures. Health-based social networking offers a mechanism for
      dissemination of such a tool and is able to embed educational messages and
      support within the process.

PMID- 23121516
TI  - Effects of carbon nanotubes, chars, and ash on bioaccumulation of
      perfluorochemicals by Chironomus plumosus larvae in sediment.
AB  - This study examined the effect of five types of carbonaceous materials (CMs) in
      sediment on bioaccumulation of perfluorochemicals (PFCs) by Chironomus plumosus
      larvae. The CMs included two multiwalled carbon nanotubes (MWCNT10 and MWCNT50),
      maize straw- and willow-derived chars, and maize straw-origin ash. The PFCs
      included perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA),
      perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic
      acid (PFUnA), and perfluorododecanoic acid (PFDoA). The CMs with different
      concentrations (0-1.5% dry weight) were amended into sediments spiked with PFCs
      and aged for 60 d. The uptake rate constants (k(s)) for each PFC to larvae
      differed with different CM amendments (p < 0.05), while elimination rate did not
      change significantly (p > 0.05). Decreasing PFC concentration in larvae (C(B))
      was found with increasing CM concentration (f(CM)) in the sediments, and a linear
      positive correlation existed between 1/C(B) and f(CM) (p < 0.05). The effect of
      CMs on PFC bioaccumulation agreed well with the CM properties; MWCNT10 with the
      highest specific surface area resulted in the lowest k(s) values and biota
      sediment accumulation factors (BSAF), with a BSAF reduction of 66%-97% by a 1.5%
      amendment. The mechanism was explored by analyzing the aqueous phase
      concentrations of PFCs and the sorption of PFCs on sediments amended with CMs.
      The results suggested that the decreasing trend of PFCs in larvae was caused by
      the decreasing aqueous phase concentration with increasing CM concentration. In
      the studied conditions with low PFC concentrations, the bioaccumulation of PFCs
      was a linear partitioning between pore water and biota, and the sorption of PFCs
      to the sediment/CM mixtures was a two domain linear distribution. This study
      suggests that both the type and concentration of carbonaceous materials in
      sediment can affect the bioaccumulation of PFCs to benthic organisms through
      changing their aqueous phase concentrations.

PMID- 23121517
TI  - Symmetry breaking during seeded growth of nanocrystals.
AB  - Currently, most of the reported noble-metal nanocrystals are limited to a high
      level of symmetry, as constrained by the inherent, face-centered cubic (fcc)
      lattice of these metals. In this paper, we report, for the first time, a facile
      and versatile approach (backed up by a clear mechanistic understanding) for
      breaking the symmetry of an fcc lattice and thus obtaining nanocrystals with
      highly unsymmetrical shapes. The key strategy is to induce and direct the growth
      of nanocrystal seeds into unsymmetrical modes by manipulating the reduction
      kinetics. With silver as an example, we demonstrated that the diversity of
      possible shapes taken by noble-metal nanocrystals could be greatly expanded by
      incorporating a series of new shapes drastically deviated from the fcc lattice.
      This work provides a new method to investigate shape-controlled synthesis of
      metal nanocrystal.

PMID- 23121518
TI  - TLR4 expression on monocyte subsets in myocardial infarction.
AB  - BACKGROUND: Monocyte toll-like receptor 4 (TLR4) has been implicated in the
      pathogenesis of atherosclerosis with increased levels in myocardial infarction.
      The aim of this study was to assess the numbers of TLR4(+)  monocytes in each
      monocyte subset in MI, the expression of TLR4 and association with markers of
      monocyte activation, inflammation, myocardial damage and postmyocardial
      infarction (MI) cardiac contractility. METHODS: Surface expression of TLR4 and
      numbers of TLR4-expressing monocytes were quantified by flow cytometry of venous
      blood in 50 patients with ST-elevation MI (STEMI), 48 with non-STEMI (NSTEMI) and
      40 with stable coronary artery disease (CAD). These parameters were measured on
      days 1, 3, 7 and 30 post-MI in STEMI patients. Three monocyte subsets were
      defined as CD14(++)  CD16(-)  CCR2(+)  (Mon1), CD14(++)  CD16(+)  CCR2(+)  (Mon2)
      and CD14(+)  CD16(++)  CCR2(-)  (Mon3). Plasma inflammatory cytokines were
      assessed using cytometric bead arrays. RESULTS: There was a significant increase
      in counts of TLR4(+)  Mon1 and Mon2 in STEMI patients and TLR4(+)  Mon2 in NSTEMI
      patients compared with controls with CAD. Monocyte TLR4(+)  expression was
      similar between the groups, and was not changed during follow-up in STEMI
      patients. Plasma interleukin-6 (IL6) levels correlated positively with TLR4(+) 
      Mon2 count (r = 0.54, P < 0.001), but negatively with TLR4 expression on Mon2 (r
      = -0.33, P = 0.021). CONCLUSION: Following treatment of acute MI, TLR4 expression
      by individual monocyte subsets is unchanged. An increase in TLR4(+)  Mon1 and
      Mon2 count in patients with STEMI and TLR(+)  Mon2 count in those with NSTEMI is
      due to an increase in monocyte subset count and not to changes in TLR4
      expression. Monocyte counts but not TLR4 expression correlate positively with
      plasma IL6 levels. We suggest that TLR4 expression may not be a reliable marker
      of monocyte activation in MI.

PMID- 23121519
TI  - Lanthanide coordination polymer nanoparticles for sensing of mercury(II) by
      photoinduced electron transfer.
AB  - The metal-organic coordination polymers at the nanoscale have emerged as
      attractive nanomaterials due to their tunable nature. In this work, we for the
      first time prepared an adenine-based lanthanide coordination polymer nanoparticle
      (CPNP) with fluorescence sensing function. This kind of CPNP was composed of
      adenine, terbium ion (Tb(3+)), and dipicolinic acid (DPA) as an auxiliary linking
      molecule that can sensitize the fluorescence of Tb(3+). The fluorescence of the
      CPNPs is very weak due to the existence of photoinduced electron transfer (PET)
      from adenine to DPA, which prevents the intramolecular energy transfer from DPA
      to Tb(3+), leading to the quench of fluorescence of the CPNPs. In the presence of
      Hg(2+), however, significant enhancement in the fluorescence of CPNPs was
      observed because of the suppression of the PET process by the coordination of
      Hg(2+) with adenine. As a kind of Hg(2+) nanosensor, the CPNPs exhibit excellent
      selectivity and ultrahigh sensitivity up to the 0.2 nM detection limit. The CPNPs
      also possess an approximately millisecond-scale-long fluorescence lifetime due to
      the inclusion of Tb(3+) ions. We envision that the CPNPs could find great
      potential applications in ultrasensitive time-resolved fluorometric assays and
      biomedical imaging in the future owing to their long emission lifetimes,
      excellent dispersion, and stability in aqueous solution.

PMID- 23121520
TI  - Parental self-efficacy and its measurement - an evaluation of a parental self
      efficacy measurement scale.
AB  - AIMS AND OBJECTIVES: To field test a parental self-efficacy scale regarding its
      acceptability and feasibility and to describe parental self-efficacy in a
      convenience sample of parents with children aged 6 years old or less. BACKGROUND:
      Self-care within families is increasingly emphasised in health policy as a means
      of maximising healthcare resources. This study reports the field testing of a
      scale designed to measure parental self-efficacy. DESIGN: Cross-sectional survey
      of parents of children aged 6 years old or less. METHODS: Subjects were recruited
      through a parenting internet website (n = 84) and local parenting and community
      organisations (n = 68) and asked to complete a questionnaire containing the
      scale. Data collection took place between January and August 2011. RESULTS: The
      scale, previously validated with an expert panel of professionals, gathered
      information about parental self-efficacy when administered either directly or
      through an on-line data collection portal, although there were more missing data
      when administered via the Internet. Although convenience and self-selecting
      samples precluded parameter estimation, areas of concern highlighted were
      difficulties differentiating children with serious illnesses and the use of the
      Personal Child Health Record. Use of the Internet was widespread, as was use of
      community pharmacists and nursery staff. CONCLUSION: Although the primary purpose
      was not to collect specific data, the data indicated the continuing concern of
      parents regarding serious illness and where additional investment may be required
      to meet parental needs and expectations. RELEVANCE TO CLINICAL PRACTICE: The
      previously validated scale can be used to collect information about parental self
      efficacy either through a paper questionnaire or the Internet. Although there was
      slightly more missing data from the Internet version, the ease of its
      administration makes this an attractive option. Parents generally reported high
      levels of self-efficacy and satisfaction with services; however, the scale was
      able to identify areas where further investment might be useful.

PMID- 23121521
TI  - Novel kinase inhibitors by reshuffling ligand functionalities across the human
      kinome.
AB  - Protein kinases remain among the most versatile and prospective therapeutic drug
      targets with currently 15 distinct compounds approved for use in humans and
      numerous clinical development programs. The vast majority of kinase inhibitors
      bind at the ATP site. Here we present an integrated workflow to amplify the
      rapidly increasing space of structurally resolved small molecule kinase ligands
      to generate novel inhibitors. Our approach considers both receptor-based
      similarity constraints in cocomplexes and ligand-based filtering/refinement
      methods to generate novel, drug-like matter. After building a comprehensive
      database of the structural kinome and identifying ATP-competitive ligands, we
      leverage local site similarities and site alignments to shuffle ligand fragments
      across the kinome. After extensive curation and standardization, our automated
      protocol starting from 936 cocrystal ATP-competitive binding sites generated
      about 150,000 new ligand structures among them over 26,000 lead-/drug-like
      compounds; the majority of those are novel based on structural similarity and
      scaffolds. In a retrospective analysis we demonstrate that our protocol produced
      known potent kinase inhibitors and we show how docking can be applied to
      prioritize the most likely efficacious compounds. Our workflow emulates a common
      strategy in medicinal chemistry to identify and swap corresponding moieties from
      known inhibitors to generate novel and potent leads. Here, we systematize and
      automate this approach leveraging available knowledge covering the entire human
      Kinome.

PMID- 23121522
TI  - Geography, ethnicity and "roots" in chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western
      countries including Israel, and is less frequent in the Orient, Asia and Middle
      Eastern Arabic speaking countries. These trends persist in migrants to other
      countries, continuing into subsequent generations. Biological and genetic
      disparities have been reported for different ethnic groups. The absence of an
      association between place of birth and the occurrence of CLL is more in line with
      a genetic basis for the geographic variations in incidence. Genetic
      predisposition to CLL is supported by the documented familial aggregation of CLL,
      with an increased frequency of 8.5-fold among first-degree relatives of patients
      with CLL and the detection of CLL-like clones in 13.5% of first-degree relatives.
      It is likely that the development of CLL depends on the interplay of a genetic
      predisposition with exposure to environmental factors. To better understand the
      interplay of ethnicity and CLL we reviewed all the available literature on ethnic
      specific differences for this common form of leukemia.

PMID- 23121523
TI  - Treating verbs in aphasia: exploring the impact of therapy at the single word and
      sentence levels.
AB  - BACKGROUND: In recent years there has been significant interest in the
      differential processing of nouns and verbs in people with aphasia, but more
      limited consideration about whether the differences have implications for
      therapy. It remains unclear whether verbs can be treated in a similar way to
      nouns or should be treated using approaches that recognize the relationship
      between verb retrieval and sentence production. AIMS: This paper reviews studies
      focusing on therapy for spoken verb retrieval, considering the impact of therapy
      on treated and untreated verbs, sentence production and connected speech. It
      explores whether there are differential gains across therapy paradigms and
      whether verbs respond to therapy in the same way as nouns. METHOD & PROCEDURES:
      Studies were identified using a systematic search. A total of 26 studies were
      reviewed and classified under four headings: (1) studies that treated verbs in a
      single-word context, (2) studies that compared treatment for nouns and verbs, (3)
      studies that treated verbs in a sentence context, and (4) studies that treated
      verb retrieval and argument structure. MAIN CONTRIBUTION: Findings from the
      review demonstrate that verb therapy, irrespective of whether verbs are treated
      within a single-word or sentence context, is effective in improving the retrieval
      of treated verbs, but with limited generalization to untreated verbs. Verbs
      respond very similarly to nouns when treated using the same techniques, but
      improving verb retrieval may be harder to achieve than improving noun retrieval.
      The impact on sentence production is more varied. The gains in sentence
      production are discussed in relation to the different therapy types, the
      rationale for therapy and the presence of co-occurring sentence difficulties.
      CONCLUSIONS: The review highlights the need for more systematic evaluation of
      different types of verb therapy, measuring the impact of therapy on verb
      retrieval, sentence production and connected speech. Only through the judicious
      assessment and monitoring of change across different contexts will an
      understanding of how verbs respond to therapy be developed and what
      generalization patterns can be predicted. This will lead to increased confidence
      in the selection of therapy approaches for people with verb difficulties in
      aphasia.

PMID- 23121525
TI  - Speech-like and non-speech lip kinematics and coordination in aphasia.
AB  - BACKGROUND: In addition to the well-known linguistic processing impairments in
      aphasia, oro-motor skills and articulatory implementation of speech segments are
      reported to be compromised to some degree in most types of aphasia. AIMS: This
      study aimed to identify differences in the characteristics and coordination of
      lip movements in the production of a bilabial closure gesture between speech-like
      and non-speech tasks in individuals with aphasia and healthy control subjects.
      METHODS & PROCEDURES: Upper and lower lip movement data were collected for a
      speech-like and a non-speech task using an AG 100 EMMA system from five
      individuals with aphasia and five age- and gender-matched control subjects. Each
      task was produced at two rate conditions (normal and fast), and in a familiar and
      a less familiar manner. Single articulator kinematic parameters (peak velocity,
      amplitude, duration and cyclic spatio-temporal index) and multi-articulator
      coordination indices (average relative phase and variability of relative phase)
      were measured to characterize lip movements. OUTCOMES & RESULTS: The results
      showed that when the two lips had similar task goals (bilabial closure) in speech
      like and non-speech task, kinematic and coordination characteristics were not
      found to be different. However, when changes in rate were imposed on the bilabial
      gesture, only speech-like task showed functional adaptations, indicated by a
      greater decrease in amplitude and duration at fast rates. In terms of group
      differences, individuals with aphasia showed smaller amplitudes and longer
      movement durations for upper lip, higher spatio-temporal variability for both
      lips, and higher variability in lip coordination than the control speakers. Rate
      was an important factor in distinguishing the two groups, and individuals with
      aphasia were limited in implementing the rate changes. CONCLUSIONS &
      IMPLICATIONS: The findings support the notion of subtle but robust differences in
      motor control characteristics between individuals with aphasia and the control
      participants, even in the context of producing bilabial closing gestures for a
      relatively simple speech-like task. The findings also highlight the functional
      differences between speech-like and non-speech tasks, despite a common movement
      coordination goal for bilabial closure.

PMID- 23121524
TI  - Effect of verb argument structure on picture naming in children with and without
      specific language impairment (SLI).
AB  - BACKGROUND: This study investigated verb argument structure effects in children
      with specific language impairment (SLI). AIMS: A picture-naming paradigm was used
      to compare the response times and naming accuracy for nouns and verbs with
      differing argument structure between Spanish-speaking children with and without
      language impairment. METHODS & PROCEDURES: Twenty-four children with SLI (ages
      5;3-8;2 [years;months]), 24 age-matched controls (ages 5;3-8;2), 24 MLU-w
      controls (ages 3;3-7;1 years), and 31 adults participated in a picture-naming
      study. OUTCOMES & RESULTS: The results show all groups produced more correct
      responses and were faster for nouns than all verbs together. As regards verb type
      accuracy, there were no differences between groups in naming one-argument verbs.
      However, for both two- and three-argument verbs, children with SLI were less
      accurate than adults and age-matched controls, but similar to the MLU-matched
      controls. For verb type latency, children with SLI were slower than both the age
      matched controls and adults for one- and two-argument verbs, while no differences
      were found in three-argument verbs. No differences were found between children
      with SLI and MLU-matched controls for any verb type. CONCLUSIONS & IMPLICATIONS:
      It has been shown that the naming of verbs is delayed in Spanish children with
      SLI. It is suggested that children with SLI may have problems encoding semantic
      representations.

PMID- 23121526
TI  - Effects of mindfulness meditation on three individuals with aphasia.
AB  - BACKGROUND: There is evidence to suggest that people with aphasia (PWA) may have
      deficits in attention stemming from the inefficient allocation of resources. The
      inaccurate perception of task demand, or sense of effort, may underlie the
      misallocation of the available attention resources. Given the lack of treatment
      options for improving attention in aphasia, Mindfulness Meditation, shown to
      improve attention in neurologically intact individuals, may prove effective in
      increasing attention in PWA. AIMS: The purpose of the present study was to
      determine if Mindfulness Meditation improves divided attention or language in PWA
      and if it affects the overall sense of effort. METHODS & PROCEDURES: A multiple
      baseline single-subject design was used to determine the effects of Mindfulness
      Meditation on divided attention for three PWA. Divided attention was measured
      using a non-linguistic divided attention task. Visual inspection of the data was
      used to determine changes in performance (sense of effort, reaction time and
      accuracy, language) over time. OUTCOMES & RESULTS: High performance observed on
      the attention measures suggests that PWA have varying degrees of attentional
      impairment that may surface when certain demands are presented. There were no
      observable changes in the performance on the sense of effort or language
      measures; however, measures of reaction time may indicate Mindfulness Meditation
      improved efficiency of task completion. CONCLUSIONS & IMPLICATIONS: All three
      participants reported that Mindfulness Meditation was easy to learn and carry out
      on a daily basis, and reported feeling more 'relaxed' and 'peaceful' after
      Mindfulness Meditation training than before. With the knowledge that PWA can
      learn meditative practices, and with such successful findings in neurologically
      intact individuals, it is important to continue evaluating the benefits of
      Mindfulness Meditation in PWA.

PMID- 23121527
TI  - Assessing the communication skills of carers working with multiple learning
      disabilities: a case study.
AB  - BACKGROUND: Speech and language therapists (SLTs) working with adults who have
      multiple learning disabilities and complex communication needs often deliver
      their care via indirect therapy where SLTs train carers to communicate with their
      clients. Yet, very little is known about how SLTs assess the carers'
      communication skills prior to the training even though the assessment should be
      the basis of this indirect therapy. AIMS: To explore the level of agreement
      between Finnish SLTs' assessments of carers as skilful communication partners for
      adults who have multiple learning disabilities and complex communication needs.
      To investigate which interaction strategies affect the SLTs' assessments. METHODS
      & PROCEDURES: Six SLTs with more than 15 years of experience in working with
      individuals with complex communication needs saw together ten video clips of
      interaction situations between a carer and an adult who had multiple learning
      disabilities (aged 17-50 years). The SLTs assessed the carers on a scale from one
      to ten. The SLTs discussed their selections before giving their final ratings.
      The data were analysed both quantitatively and qualitatively. The unanimity of
      SLTs' assessment was analysed with a test of Kendall's W. Furthermore, the
      frequencies of the carers' different communication acts were counted and these
      counts were compared with the mean of the carers' assessments. These results were
      further explored with the SLTs' justifications about their assessments. OUTCOMES
      & RESULTS: SLTs did not fully agree on which of the carers were the most skilful
      interaction partners. Furthermore, the six SLTs were not unanimous about which
      carers' interaction strategies resulted in skilful communication. However, SLTs
      assessed those carers higher who used facilitative verbal acts. The carers used
      these verbal acts to involve themselves in the interests of the client.
      CONCLUSIONS & IMPLICATIONS: This case study showed that Finnish SLTs seem to have
      different criteria about what is considered skilful communication between carers
      and clients who have multiple learning disabilities. Even though there might not
      be a single way of being a skilful interaction partner, this variable can be
      confusing to carers if they work with several SLTs and each of them offers
      different professional advice. Therefore, the results suggest a need for an
      assessment tool for evaluating the carers' interaction skills. In addition to
      this tool, it appears that SLTs also need further training to be able to perform
      this multifaceted task.

PMID- 23121528
TI  - The working practices and clinical experiences of paediatric speech and language
      therapists: a national UK survey.
AB  - BACKGROUND: The majority of speech and language therapists (SLTs) work with
      children who have speech, language and communication needs. There is limited
      information about their working practices and clinical experience and their views
      of how changes to healthcare may impact upon their practice. AIMS: To investigate
      the working practices and professional experiences of paediatric SLTs working in
      the UK through an online survey. METHODS & PROCEDURES: The survey was conducted
      online using Survey Monkey. Therapists were alerted to the survey through the
      Bulletin of the Royal College of Speech and Language Therapists and by e-mails to
      national special interest groups. OUTCOMES & RESULTS: A total of 516 clinicians
      completed the survey. A large majority worked in the National Health Service
      (NHS). A varied pattern of working was revealed. Most worked in several settings
      and saw a range of clients. A typical clinician spends less than one-quarter of
      their time giving direct therapy and more than one-quarter training parents and
      other professionals. Nearly half of respondents felt that their time could be
      better used. Too little time for direct therapy and the time required for
      administration emerged as their principal concerns. Most clinicians have
      specialist knowledge of particular client groups and spend more time with them
      than do non-specialists. Nevertheless, clients are more likely to be treated by a
      therapist who does not claim to have specialist knowledge of their condition than
      by one who does. The only clients for whom this is not the case are those with
      dysphagia. Eighty per cent of respondents felt that proposed changes to the NHS
      would not benefit the children they treat and there was widespread concern about
      cuts and the effects of general practitioner commissioning. Despite this, a large
      majority expected to remain speech and language therapists 5 years from now.
      CONCLUSIONS & IMPLICATIONS: This survey provides an overview of the working
      practices of paediatric speech and language therapists. Its findings have
      significant implications for training and workforce development in the
      profession.

PMID- 23121529
TI  - The living with dysarthria group: implementation and feasibility of a group
      intervention for people with dysarthria following stroke and family members.
AB  - BACKGROUND: The broad life implications of acquired dysarthria are recognized,
      but they have received little attention in stroke management. Reports of group
      therapy, which may be a suitable approach to intervention, are not available for
      stroke-related dysarthria. AIMS: To examine the operational feasibility of and
      response to a new eight-session weekly group intervention programme, Living with
      Dysarthria, designed for people with chronic dysarthria following stroke and
      their main communication partners. METHODS & PROCEDURES: The target participation
      was for programme completion by two groups of eight people with dysarthria (PWD)
      and available family members (FMs) or carers. An active recruitment strategy was
      undertaken from the speech and language therapy case records for the previous 6
      years in two hospitals with combined annual stroke admissions of over 500 people.
      Twelve PWD and seven FMs were recruited (group 1: seven PWD and four FMs; group
      2: five PWD and three FMs). Speech intelligibility, communication effectiveness,
      general well-being, quality of communication life, and knowledge of stroke and
      dysarthria were assessed pre- and post-programme. Each PWD and FM also set an
      individual goal and rated their achievement of this on a 0-10 scale. OUTCOMES &
      RESULTS: Recruitment to the programme was lower than anticipated and below
      target. The 12 PWD were recruited from 62 initial contacts, which was the total
      number who according to available information met the criteria. The programme was
      viable: it ran to plan, with only minor content alterations, in community
      accommodation, and with good participant engagement. Group median score changes
      were in a positive direction for all measures and effect sizes ranged from 0.17
      (quality of communication life) to 0.46 (intelligibility). Significant post
      programme changes were present for intelligibility and knowledge of stroke and
      dysarthria (p= 0.05). Participants' ratings of goal achievements ranged from 6
      (some change) to 10 (a lot of change). CONCLUSIONS & IMPLICATIONS: The
      recruitment experience revealed a take-up rate of around 20% from PWD following
      stroke, informing future planning. The participant engagement and performance
      results from the piloting of the programme indicate that the Living with
      Dysarthria programme is viable and has potential for effecting positive change.
      Further testing is justified.

PMID- 23121530
TI  - Survey of UK speech and language therapists' assessment and treatment practices
      for people with progressive dysarthria.
AB  - BACKGROUND: Dysarthria knowledge is predominantly impairment-based. As a result,
      speech and language therapists (SLTs) have traditionally adopted impairment
      focused management practices. However, guidance for best practice suggests that
      SLTs should consider the client holistically, including the impact of dysarthria
      beyond the impairment. AIMS: To investigate the current assessment and treatment
      practices used by UK SLTs with clients with progressive dysarthria and to
      identify whether these satisfy the needs of SLTs in their everyday practice. To
      investigate the extent to which they consider oromotor abilities,
      intelligibility, functional communication, participation and interaction to be
      important regarding assessment and treatment decisions. To explore whether
      management decisions are affected by level of clinical experience or settings in
      which SLTs work. METHODS & PROCEDURES: An online survey of UK SLTs working with
      adults with progressive dysarthria. OUTCOMES & RESULTS: A total of 119 SLTs
      completed the survey. Respondents considered that targeting the levels of
      impairment, activity and participation are important in the management of clients
      with progressive dysarthria, as recommended by clinical guidelines and recent
      research. However a particularly high proportion of respondents reported the use
      of impairment-based assessments. Respondents reported lacking the necessary tools
      to target interaction in assessment and intervention. The intervention that
      respondents use with clients varies according to the progressive disorder and
      dysarthria severity. There is evidence for a trend that less experienced SLTs and
      those working predominantly in hospital-based settings focus on the impairment,
      whereas more SLTs with more experience and those based in predominantly community
      based settings look beyond the impairment. CONCLUSIONS & IMPLICATIONS: The values
      held by SLTs match guideline recommendations for best practice, however the
      clinical reality is that the assessment of progressive dysarthria remains
      predominantly impairment-focused. New tools need to be developed and integrated
      into practice to target interaction in assessment and intervention, to reduce the
      gap between best practice recommendations and clinical reality. Ongoing research
      into the effectiveness of SLT intervention with clients with progressive
      dysarthria is required to guide clinical management decisions.

PMID- 23121531
TI  - Phonological and phonetic marking of information status in Foreign Accent
      Syndrome.
AB  - BACKGROUND: Foreign Accent Syndrome (FAS) is a motor speech disorder in which a
      variety of segmental and suprasegmental errors lead to the perception of a new
      accent in speech. Whilst changes in intonation have been identified to contribute
      considerably to the perceived alteration in accent, research has rarely focused
      on how these changes impact on the pragmatic use of intonation. However, a
      greater understanding of the role of intonational changes in FAS and its impact
      on the functional use of intonation is fundamental to developing appropriate
      assessment and subsequently treatment strategies for FAS. AIMS: This study
      investigated intonation patterns in speakers with FAS and matched control
      participants with regard to their ability to signal new and given information
      (information status) within sentences. A phonetic and phonological perspective
      was taken with the aim of identifying the characteristics that were compromised
      in FAS to convey this linguistic function. METHODS & PROCEDURES: Four speakers
      with FAS and four control participants participated in the speech production
      experiment. The speech data were assessed perceptually, and examined in relation
      to the use of the phonetic parameters fundamental frequency (f0), intensity and
      duration as well as phonological categories, i.e. pitch accents and de
      accentuation, using the autosegmental-metrical (AM) framework of intonational
      analysis. OUTCOMES & RESULTS: Both speaker groups employed all three phonetic
      parameters to differentiate between new and given information. However, groups
      differed regarding the use of phonological markers, with speakers with FAS
      frequently placing pitch accents on given information instead of de-accenting
      these elements. According to the perceptual evaluation, three of the four
      speakers with FAS had problems signalling information status. CONCLUSIONS &
      IMPLICATIONS: The fact that speakers with FAS marked information status similarly
      to control speakers at the phonetic level, but failed to do so using phonological
      categories highlights the importance of assessing phonetic as well as
      phonological features to gain detailed information about the functional use of
      intonation in FAS.

PMID- 23121532
TI  - Effective and minimally traumatic insertion of the Blom-Singer(r) Large
      Oesophageal Flange speech prosthesis.

PMID- 23121533
TI  - Regarding "Syrnyk, C. and Meints, K., 2012, Fishy fishes: the typicality of
      object stimuli used to assess children's language in the Reynell Development
      Language Scales - III.

PMID- 23121536
TI  - Management of myocardial ischemia. Is ranolazine needed? For all or some patients
      with myocardial ischemia?
AB  - This editorial refers to 'Should ranolazine be used for all patients with
      ischemic heart disease or only for symptomatic patients with stable angina or for
      those with refractory angina pectoris? A critical appraisal' by U Thadani also
      published in this issue.

PMID- 23121537
TI  - Oxidative stress and the DNA mismatch repair pathway.
AB  - SIGNIFICANCE: Living organisms are under constant assault by a combination of
      environmental and endogenous oxidative DNA damage, inducing the modification of
      proteins, lipids, and DNA. Failure to resolve these oxidative modifications is
      associated with genome instability and the development of many disease states. To
      maintain genomic integrity, oxidative lesions must be precisely targeted and
      efficiently resolved. For this, cells have evolved an intricate network of DNA
      repair mechanisms to detect and repair oxidative DNA damage. RECENT ADVANCES:
      Emerging evidence suggests that in addition to the base excision repair and
      nucleotide excision repair pathways, the DNA mismatch repair (MMR) pathway plays
      an important role in mediating oxidative DNA damage repair. Studies in lower
      organisms and mammalian cells have enabled us to further dissect this critical
      role and elucidate the precise mechanisms of repair. CRITICAL ISSUES:
      Identification of synthetic lethal interactions between MMR deficiency and the
      accumulation of oxidative DNA damage raises the tantalizing prospect that
      oxidative DNA-damaging agents may be utilized to selectively target MMR-deficient
      cancers and potentially other tumor types deficient for oxidative DNA repair
      molecules. FUTURE DIRECTIONS: In this review, we emphasize the clinical relevance
      and potential translation of exploiting this oxidative DNA repair mechanism using
      synthetic lethality studies in MMR-deficient cells, to develop improved treatment
      strategies that will benefit cancer patients.

PMID- 23121542
TI  - Mechanistic and computational studies of exocyclic stereocontrol in the synthesis
      of bryostatin-like cis-2,6-disubstituted 4-alkylidenetetrahydropyrans by Prins
      cyclization.
AB  - The Prins cyclization of syn-beta-hydroxy allylsilanes and aldehydes gives cis
      2,6-disubstituted 4-alkylidenetetrahydropyrans as sole products in excellent
      yields regardless of the aldehyde (R") or syn-beta-hydroxy allylsilane
      substituent (R') used. By reversing the R" and R' groups, complementary exocyclic
      stereocontrol can be achieved. When the anti-beta-hydroxy allylsilanes are used,
      the Prins cyclization gives predominantly cis-2,6-disubstituted 4
      alkylidenetetrahydropyrans, now with the opposite olefin geometry in excellent
      yield. The proposed reaction mechanism and the observed stereoselectivity for
      these processes are supported by DFT calculations.

PMID- 23121544
TI  - Direct measurement of the thermal hysteresis of antifreeze proteins (AFPs) using
      sonocrystallization.
AB  - Antifreeze proteins (AFPs) are of great importance for applications in
      cryomedicine or the food industry. They are frequently used to lower the freezing
      point by preventing the growth of larger ice crystals; thus, it is paramount to
      determine their thermal hysteretic characteristics. However, the experimental
      analysis of the thermal hysteresis-an effect that is characteristic for AFPs
      remains a challenging process. An easy-to-use test method for measuring the
      thermal hysteresis of AFPs was developed and tested with the type III AFPs.
      Traditional methods that have been used until now have their disadvantages and
      limitations. The new measurement method described in this paper allows detection
      of the complete cooling, freezing, heating, and melting process in a single
      measurement. This makes it possible to directly determine the thermal hysteresis
      as a functional effect of the antifreeze proteins. Measurements of the thermal
      hysteresis were performed by applying ultrasound to initiate the crystallization
      process of the antifreeze protein solution. This ultrasound technique also allows
      a crystallization process to be performed at defined temperature. The
      demonstrated results were highly reproducible and could be clearly read off the
      measurement curves. As a future perspective, this enables the design of automatic
      test devices that can be also miniaturized.

PMID- 23121543
TI  - Agraphia in patients with frontotemporal dementia and parkinsonism linked to
      chromosome 17 with P301L MAPT mutation: dysexecutive, aphasic, apraxic or spatial
      phenomenon?
AB  - OBJECTIVES: Patients with frontotemporal dementia and parkinsonism linked to
      chromosome 17 (FTDP-17) may be agraphic. The study aimed at characterizing
      agraphia in individuals with a P301L MAPT mutation. METHODS: Two pairs of
      siblings with FTDP-17 were longitudinally examined for agraphia in relation to
      language and cognitive deficits. RESULTS: All patients presented with
      dysexecutive agraphia. In addition, in the first pair of siblings one sibling
      demonstrated spatial agraphia with less pronounced allographic agraphia and the
      other sibling had aphasic agraphia. Aphasic agraphia was also present in one
      sibling from the second pair. CONCLUSION: Agraphia associated with FTDP-17 is
      very heterogeneous.

PMID- 23121545
TI  - Pretend play, deferred imitation and parent-child interaction in speaking and non
      speaking children with autism.
AB  - This study investigates spontaneous pretend play during a parent-child free play
      observation, and deferred imitation observed in an experimental setting in
      speaking and non-speaking children with autism in comparison to children with
      typical development. Both groups of children with autism showed a reduced level
      of deferred imitation compared to the typically developing group, but only the
      non-speaking children with autism spent significantly less time in pretend play
      compared to children with typical development. Deferred imitation was related to
      parents' verbal interaction in both groups. An analysis of the parent-child
      interaction revealed that parents of children with autism used less synchronized
      comments compared to parents of typically developing children. Parents of the
      speaking group with autism used more synchronized than unsynchronized comments,
      while parents of the non-speaking group used the same amount of synchronized and
      unsynchronized comments. These findings are discussed in terms of how the
      developmental level affects behavior and interaction in autism.

PMID- 23121547
TI  - Time to act against Clostridium difficile infection.

PMID- 23121546
TI  - Oncogenic potential of cyclin kinase subunit-2 in cholangiocarcinoma.
AB  - BACKGROUND: Cyclin kinase subunit-2 (Cks2), a member of the human Cks family,
      plays an important role in the regulation of meiosis and mitosis; and its
      abnormal expression is usually associated with carcinogenesis. However, its exact
      functions and molecular mechanisms remain unclear. AIMS: To observe Cks2
      expression in cholangiocarcinoma and explore its role in the carcinogenesis of
      cholangiocarcinoma and possible mechanism. METHODS: Cks2 expression in
      cholangiocarcinoma was detected with immunostaining and RT-PCR. MTT, colony
      formation, immunofluorescence, flow cytometry and Western blotting were performed
      to explore the role of Cks2 in cholangiocarcinoma and possible mechanism.
      RESULTS: Cks2 was significantly elevated in cholangiocarcinoma tissues and its
      over-expression was associated with poor differentiation, CA19-9 and poor
      prognosis. Furthermore, Cks2 down-regulation inhibited cholangiocarcinoma cell
      proliferation and colony formation in vitro, and the growth of cholangiocarcinoma
      xenografts in animals; especially, enhanced the sensitivity of cholangiocarcinoma
      cells to chemotherapy. We further found that Cks2 knockdown induced
      cholangiocarcinoma cell cycle arrest in G2/M phase through down-regulation of
      Cyclin A and Cyclin B1 and Bax up-regulation and activation, mitochondrial
      membrane permeabilization and caspase-3 activation, which resulted in
      facilitating cholangiocarcinoma apoptosis. CONCLUSIONS: These findings suggest
      that Cks2 may serve as an independent prognostic factor in patients with
      cholangiocarcinoma, and play an important role in the carcinogenesis of
      cholangiocarcinoma by facilitating cell cycle progression and Bax-mediated
      mitochondrial caspase-dependent apoptosis.

PMID- 23121548
TI  - Breaking the cycle of recurrent Clostridium difficile infections.

PMID- 23121549
TI  - Consequences of Clostridium difficile infection: understanding the healthcare
      burden.
AB  - Clostridium difficile is the leading cause of infectious nosocomial diarrhoea in
      developed countries, with a measured incidence of approximately five episodes per
      10,000 days of hospital stay in Europe. Accurate diagnosis of C. difficile
      infection (CDI) is a prerequisite for obtaining reliable epidemiological data,
      but in many European countries diagnosis is probably suboptimal. A significant
      percentage of CDI cases are missed because clinicians often fail to request tests
      for C. difficile toxins in cases of unexplained diarrhoea. In addition, some
      laboratories continue to use tests of low sensitivity or apply them
      inappropriately. In one study in Spain, failure to request CDI testing in more
      than two-thirds of patients with unexplained diarrhoea led to significant
      underdiagnosis of cases. A recent pan-European survey revealed huge discrepancies
      in the rate of CDI testing across Europe, which suggests that epidemiological
      reports underestimate the true incidence of CDI in many parts of Europe. This is
      important because, as this review of the clinical and economic burden of CDI
      illustrates, infection with C. difficile imposes a significant burden not only on
      patients, owing to increased morbidity and mortality, but also on healthcare
      systems and society in general. On the basis of current incidence rates, annual
      costs for management of CDI amount to approximately $800 million in the USA and
      ?3000 million in Europe. Moreover, estimates suggest that costs associated with
      recurrent CDI can exceed those of primary CDI. Measures to more effectively
      prevent CDI and reduce CDI recurrence rates may help to reduce this burden.

PMID- 23121550
TI  - Overcoming barriers to effective recognition and diagnosis of Clostridium
      difficile infection.
AB  - With the frequency of cases of Clostridium difficile infection (CDI) increasing
      in many developed countries, accurate and reliable laboratory diagnosis of CDI is
      more important than ever. However, the diagnosis of CDI has been handicapped by
      the existence of two reference standards, one of which detects C. difficile toxin
      (cytotoxin assay) and the other only toxigenic strains (cytotoxigenic culture).
      Being relatively slow and laborious to perform, these reference methods were
      largely abandoned as routine diagnostic methods for toxin detection in favour of
      stand-alone rapid enzyme immunoassays (EIAs), which have suboptimal sensitivity
      and specificity. The management of CDI is undermined by high rates of both false
      positive and false-negative test results. More recently developed nucleic acid
      amplification tests (NAATs) for toxin gene detection offer improved sensitivity
      over immunoassays, but fail to discriminate between CDI and asymptomatic
      colonization with C. difficile, and have clear drawbacks as stand-alone
      diagnostic tests. Two-step or three-step diagnostic algorithms have been proposed
      as a solution. In a large study of the effectiveness of currently available
      tests, a diagnostic algorithm was developed that combines available tests to more
      effectively distinguish patients with CDI from uninfected patients. This two-test
      protocol, which is now used in National Health Service laboratories in England,
      comprises an EIA for glutamate dehydrogenase detection or NAATs for toxin gene
      detection, followed by a relatively sensitive toxin EIA. This algorithm also
      identifies 'potential C. difficile excretors', individuals with diarrhoeal
      samples that contain C. difficile but without demonstrable toxin, who may be a
      source of transmission of C. difficile to susceptible patients.

PMID- 23121551
TI  - Can we identify patients at high risk of recurrent Clostridium difficile
      infection?
AB  - Although most patients with Clostridium difficile infection (CDI) can be managed
      effectively with discontinuation of prescribed antibiotics and additional
      treatment with oral metronidazole or vancomycin, up to 25% experience disease
      recurrence, usually within 30 days of treatment. Failure to mount a systemic anti
      toxin antibody response differentiates patients with CDI and recurrent CDI from
      symptomless carriers of toxinogenic C. difficile. The immunological senescence
      that accompanies ageing may lead to impaired immune responses to C. difficile and
      contribute to the significant association between advancing age and increased
      risk of CDI recurrence. Inadequate immunity may also explain why previous
      episodes of recurrence constitute a significant risk factor for further CDI
      recurrences. Other risk factors for recurrent CDI include concurrent use of
      antibiotics for non-C. difficile infections (which perpetuate the loss of
      colonization resistance), proton-pump inhibitors, and other gastric acid anti
      secretory medications, prolonged hospitalization, and severe underlying illness
      (as reflected by a high Horn index score). Prominent risk factors have been
      examined to develop and validate a clinical prediction tool for recurrent CDI,
      with three factors (age >65 years, severe underlying disease (by the Horn index
      score), and continued use of antibiotics for non-CDI infections) being highly
      predictive of CDI recurrence. Such simple clinical prediction rules have the
      potential to identify patients at high risk of recurrent CDI, and can alert the
      treating physician to the need for prompt recognition, confirmatory diagnosis and
      treatment with regimens ideally designed to mitigate the risk of subsequent
      recurrences.

PMID- 23121552
TI  - Current and emerging management options for Clostridium difficile infection: what
      is the role of fidaxomicin?
AB  - Until recently, treatment of Clostridium difficile infection (CDI) was mainly
      limited to oral metronidazole and vancomycin, neither of which is optimal. Up to
      25% of patients with CDI experience recurrence of infection within 30 days
      following treatment with these agents, while c. 45-65% of these patients
      experience further (and sometimes multiple) recurrences. Recurrent CDI represents
      a major treatment challenge for which new therapeutic options are sorely needed.
      Fidaxomicin is a first-in-class, oral macrocyclic antibiotic with targeted
      bactericidal activity against C. difficile and minimal effect on the constituents
      of the normal colonic microflora. This microflora-sparing activity allows for
      more rapid restoration of the normal colonic microflora in patients with CDI. In
      two separate, but almost identical, phase 3 clinical trials in which patients
      with CDI were treated with either fidaxomicin or vancomycin, fidaxomicin
      demonstrated superior clinical outcomes in comparison with the current best
      available treatment. While non-inferiority was demonstrated with respect to rates
      of clinical cure at end of treatment, significantly fewer fidaxomicin-treated
      patients experienced disease recurrence, which translated into clinically
      significant improvements in sustained clinical cure. Subsequent sub-population
      analyses suggest that these benefits extend to older patients, patients with
      severe CDI, renally impaired patients and patients with a prior episode of CDI.
      For CDI patients receiving concomitant antibiotics, fidaxomicin achieved
      significantly better rates of clinical cure and sustained clinical cure than
      vancomycin recipients. Fidaxomicin has a safety profile similar to oral
      vancomycin and appears generally well tolerated. Fidaxomicin represents an
      important addition to current treatment options for CDI.

PMID- 23121553
TI  - Comparison of anticipatory grief reaction between fathers and mothers of
      premature infants in neonatal intensive care unit.
AB  - OBJECTIVES: Premature birth of neonates leads to anticipatory grief (AG) reaction
      in parents and make them vulnerable to mental health disorders. The present study
      aimed to determine and compare the AG reaction in mothers and fathers of
      premature infants hospitalized in the neonatal intensive care unit. METHODS: This
      comparative descriptive design was conducted among 40 pairs of mothers and
      fathers selected by convenience sampling method. The study was performed in 2011
      using the Anticipatory Grief Scale. Data were analysed with 'Wilcoxon ranks test'
      using SPSS. RESULTS: The AG mean scores of fathers and mothers were 1.55 +/- 0.55
      and 1.68 +/- 0.63, respectively. The Wilcoxon test did not show any statistically
      significant difference between mothers' and fathers' AG reaction (p = 0.12).
      CONCLUSION: Despite expectations, the AG reaction in mothers and fathers showed
      no difference in this study. It seems necessary to pay more attention to the
      fathers in addition to mothers to be supported and consulted by the healthcare
      providers.

PMID- 23121554
TI  - Prenatal family adversity and maternal mental health and vulnerability to peer
      victimisation at school.
AB  - BACKGROUND: Prenatal stress has been shown to predict persistent behavioural
      abnormalities in offspring. Unknown is whether prenatal stress makes children
      more vulnerable to peer victimisation. METHODS:  The current study is based on
      the Avon Longitudinal Study of Parents and Children, a prospective community
      based study. Family adversity, maternal anxiety and depression were assessed at
      repeated intervals in pregnancy and the postnatal period. Parenting, partner
      conflict and temperament were measured at preschool age. Peer victimisation was
      assessed using multiple informants (child, parent, teacher) at primary school age
      (between ages 7 and 10). RESULTS: Prenatal severe family adversity and maternal
      mental health directly increased the risk of victimisation at school even when
      controlled for postnatal family adversity and maternal mental health, parenting,
      partner conflict and temperament. Effects were found to be independent of sources
      of information of peer victimisation. Partner conflict and maladaptive parenting
      also independently increased the risk of peer victimisation. CONCLUSIONS:
      Experiences in pregnancy may affect the developing foetus and increase
      vulnerability to be victimised by peers. Conflict between parents and their
      parenting further increase the risk of being victimised by peers at school.

PMID- 23121555
TI  - Immediate allergic cross-reactivity to levobupivacaine and ropivacaine.
AB  - Allergic reactions to amide local anaesthetic agents are rare. We report the case
      of a 74-year-old man who suffered anaphylaxis, presenting with cardiovascular
      collapse, immediately after receiving regional anaesthesia on two separate
      occasions, the first involving the use of levobupivacaine and the second using
      ropivacaine. Skin testing revealed positive reactions to both levobupivacaine and
      ropivacaine, and negative reactions to articaine and lidocaine. Severe allergic
      reactions can be caused by the amide local anaesthetic drugs, levobupivacaine and
      ropivacaine.

PMID- 23121556
TI  - Erythema nodosum induced by kerion celsi of the scalp in a child: a case report
      and mini-review of literature.
AB  - A 9-year-old girl, presented with a 4-week history of an inflammatory suppurative
      plaque, 8 cm in diameter, localised in the occipital area of the scalp.
      Mycological direct examination showed ectoendothrix invasion of the hair and
      Trichophyton mentagrophytes was isolated. Oral therapy with griseofulvin 25 mg
      kg(-1)  day(-1) was prescribed, but after 2 weeks of treatment appeared multiple
      erythematous subcutaneous nodules localised in the legs. Erythema nodosum (EN)
      was confirmed by histological examination of a nodule and then we combined
      therapy with 1 mg Kg(-1)  day(-1) of prednisone. At the remission of the
      panniculitis, which occurred in about 10 days, the steroid therapy was suspended,
      while the orally administered griseofulvin continued for 6 weeks until full
      recovery. EN is the most frequent clinical form of acute nodular panniculitis and
      it is considered an epiphenomenon relative to various infectious and non
      infectious stimuli. The association of EN with dermatophytosis of the scalp is
      infrequent, with only 15 cases reported in the Literature.

PMID- 23121558
TI  - Enhanced AV nodal conduction and Brenchenmacher tracts.

PMID- 23121557
TI  - Inhibition of CXCR3-mediated chemotaxis by the human chemokine receptor-like
      protein CCX-CKR.
AB  - BACKGROUND AND PURPOSE: Induction of cellular migration is the primary effect of
      chemokine receptor activation. However, several chemokine receptor-like proteins
      bind chemokines without subsequent induction of intracellular signalling and
      chemotaxis. It has been suggested that they act as chemokine scavengers, which
      may control local chemokine levels and contribute to the function of chemokines
      during inflammation. This has been verified for the chemokine-like receptor
      proteins D6 and DARC as well as CCX-CKR. Here, we provide evidence for an
      additional biological function of human (h)CCX-CKR. EXPERIMENTAL APPROACH: We
      used transfection strategies in HEK293 and human T cells. KEY RESULTS: Co
      expression of hCCX-CKR completely inhibits hCXCR3-induced chemotaxis. We found
      that hCCX-CKR forms complexes with hCXCR3, suggesting a relationship between CCX
      CKR heteromerization and inhibition of chemotaxis. Moreover, negative binding
      cooperativity induced by ligands both for hCXCR3 and hCCX-CKR was observed in
      cells expressing both receptors. This negative cooperativity may also explain the
      hCCX-CKR-induced inhibition of chemotaxis. CONCLUSIONS AND IMPLICATIONS: These
      findings suggest that hCCX-CKR prevents hCXCR3-induced chemotaxis by
      heteromerization thus representing a novel mechanism of regulation of immune cell
      migration.

PMID- 23121559
TI  - Bisolute sorption and thermodynamic behavior of organic pollutants to biomass
      derived biochars at two pyrolytic temperatures.
AB  - The bisolute sorption and thermodynamic behavior of organic pollutants on low
      temperature biochars (LTB) at 300  degrees C and high temperature biochars (HTB)
      at 700  degrees C were determined to elucidate sorptive properties of biochar
      changed with pyrolytic temperatures. The structural characteristics and isotherms
      shape of the biochar were more dependent on the pyrolytic temperature than on the
      biomass feedstocks, which included orange peel, pine needle, and sugar cane
      bagasse. For LTB, the thermally altered organic matter colocalized with the
      carbonized matter, and the visible fine pores of the fixed carbons were plugged
      by the remaining volatile carbon. For HTB, most of the volatile matter was gone
      and the fixed matter was composed of fully carbonized adsorptive sites. Monolayer
      adsorption of 1-naphthol to HTB was dominant but was suppressed by phenol. In
      comparison, LTB displayed exceptional sorption behavior where partition and
      adsorption were concurrently promoted by a cosolute and elevated temperature. In
      addition to monolayer surface coverage, pore-filling mechanisms may contribute to
      the increase of adsorption fraction. Moreover, the entropy gain was a dominant
      force driving the partition and adsorption processes in LTB. Thus, the
      colocalizing partition phase and adsorptive sites in LTB are proposed to be in
      interencased states rather than in physical separation.

PMID- 23121560
TI  - Pulling peptides across nanochannels: resolving peptide binding and translocation
      through the hetero-oligomeric channel from Nocardia farcinica.
AB  - We investigated translocation of cationic peptides through nanochannels derived
      from the Gram-positive bacterium Nocardia farcinica at the single-molecule level.
      The two subunits NfpA and NfpB form a hetero-oligomeric cation selective channel.
      On the basis of amino acid comparison we performed homology modeling and obtained
      a channel structurally related to MspA of Mycobacterium smegmatis. The
      quantitative single-molecule measurements provide an insight into transport
      processes of solutes through nanochannels. High-resolution ion conductance
      measurements in the presence of peptides of different charge and length revealed
      the kinetics of peptide binding. The observed asymmetry in peptide binding
      kinetics indicated a unidirectional channel insertion in the lipid bilayer. In
      the case of cationic peptides, the external voltage acts as a driving force that
      promotes the interaction of the peptide with the channel surface. At low voltage,
      the peptide just binds to the channel, whereas at higher voltage, the force is
      strong enough to pull the peptide across the channel. This allows distinguishing
      quantitatively between peptide binding and translocation through the channel.

PMID- 23121561
TI  - Does self-reported physical activity associate with high blood pressure in
      adolescents when adiposity is adjusted for?
AB  - Studies show that both low physical activity (PA) and adiposity are associated
      with a higher risk of hypertension. However, the relationship between PA and
      blood pressure in adolescents is controversial and other studies have reported
      that no association was observed. Of particular interest is the evaluation of
      whether the association between PA and high blood pressure is independent of
      adiposity. A sample of 3764 Brazilian adolescents who attend high schools was
      selected using random cluster sampling. Data were collected using the Global
      School-based Student Health Survey, anthropometry, and blood pressure readings.
      The prevalence of high blood pressure was 14.6% (95% Confidence Interval (CI)
      13.5-15.7), higher amongst males (20.0%; 95%CI 18.0-22.1) compared with females
      (10.9%; 95%CI 9.7-12.3). Sixty-six per cent of the adolescents were reported to
      be insufficiently active. The prevalence of high blood pressure was 12.8% (95%CI
      11.0-14.7) amongst active compared with 15.4% (95%CI 14.0-16.9) amongst
      insufficiently active adolescents. The association between PA and high blood
      pressure was observed only amongst females after adjusting for waist
      circumference (odds ratio (OR) 1.67; 95%CI 1.21-2.31) and body mass index (OR
      1.71; 95%CI 1.23-2.37). Notwithstanding levels of adiposity, higher PA levels are
      associated with a lower prevalence of high blood pressure amongst females,
      although not amongst males.

PMID- 23121562
TI  - Synthesis of peptides containing C-terminal methyl esters using trityl side-chain
      anchoring: application to the synthesis of a-factor and a-factor analogs.
AB  - A new cysteine anchoring method was developed for the synthesis of peptides
      containing C-terminal cysteine methyl esters. This method consists of attachment
      of Fmoc-Cys-OCH(3) to either 2-ClTrt-Cl or Trt-Cl resins (via the side-chain
      thiol) followed by preparation of the desired peptide using Fmoc-based SPPS. We
      applied this method to the synthesis of the mating pheromone a-factor and a 5-FAM
      labeled a-factor analog. The peptides were obtained with high yield and purity
      and were shown to be bioactive in a growth arrest assay.

PMID- 23121563
TI  - Intraoperative transfusion threshold and tissue oxygenation: a randomised trial.
AB  - BACKGROUND AND OBJECTIVES: Transfusion with allogeneic red blood cells (RBCs) may
      be needed to maintain oxygen delivery during major surgery, but the appropriate
      haemoglobin (Hb) concentration threshold has not been well established. We
      hypothesised that a higher level of Hb would be associated with improved
      subcutaneous oxygen tension during major spinal surgery. MATERIALS AND METHODS:
      Fifty patients aged 18 years or older scheduled for spinal fusion with
      instrumentation were included and randomised to receive RBCs at either a Hb
      concentration of 7.3 g dL(-1) (restrictive group) or a Hb concentration of 8.9 g
      dL(-1) (liberal group) (Registration no.: H-C-2009-072). Oxygen tension was
      measured with a polarographic electrode placed subcutaneously over the left
      deltoid muscle. The primary endpoint was subcutaneous oxygen tension at the time
      most patients were still undergoing surgery. RESULTS: Forty-eight patients were
      included in the intention-to-treat analysis; 25 patients in the restrictive group
      and 23 patients in the liberal group. The median change in subcutaneous oxygen
      tension 60 min after surgical incision was -0.79 and -0.75 kPa in the restrictive
      and the liberal groups, respectively (P = 0.78). No significant difference was
      found in the lowest subcutaneous oxygen tension; -2.07 vs. -1.95 kPa in the
      restrictive and the liberal groups, respectively (P = 0.85). CONCLUSION: A Hb
      concentration transfusion threshold of 8.9 g dL(-1) was not associated with a
      higher subcutaneous oxygen tension during major spinal surgery than a threshold
      of 7.3 g dL(-1), but the trial was compromised by methodological difficulties.

PMID- 23121564
TI  - SAR103168: a tyrosine kinase inhibitor with therapeutic potential in myeloid
      leukemias.
AB  - SAR103168, a tyrosine kinase inhibitor of the pyrido [2,3-d] pyridimidine
      subclass, inhibited the kinase activities of the entire Src kinase family, Abl
      kinase, angiogenic receptor kinases (vascular endothelial growth factor receptor
      [VEGFR] 1 and 2), Tie2, platelet derived growth factor (PDGF), fibroblast growth
      factor receptor (FGFR) 1 and 3, and epidermal growth factor receptor (EGFR).
      SAR103168 was a potent Src inhibitor, with 50% inhibitory concentration (IC50) =
      0.65 +/- 0.02 nM (at 100 MUM ATP), targeting the auto-phosphorylation of the
      kinase domain (Src(260-535)) and activity of the phosphorylated kinase.
      Phosphorylation of Src, Lyn and Src downstream signaling pathways (PYK2, P
      130CAS, FAK, JNK and MAPK) were inhibited in a dose-dependent manner. SAR103168
      inhibited the phosphorylation of STAT5 in KG1 cells and fresh cells from patients
      with acute myeloid leukemia (AML). SAR103168 inhibited proliferation and induced
      apoptosis in acute and chronic myeloid leukemic cells at nanomolar IC50.
      SAR103168 induced anti-proliferation of leukemic progenitors (CFU-L) from 29
      patients with AML, and > 85% of AML patient samples were sensitive to SAR103168.
      These antagonist activities of SAR103168 were independent of FLT3 expression.
      SAR103168 treatment was effective in 50% of high-risk patient samples carrying
      chromosome 7 abnormalities or complex rearrangement. SAR103168 administration
      (intravenous or oral) impaired tumor growth and induced tumor regression in
      animals bearing human AML leukemic cells, correlating with potent inhibition of
      Src downstream signaling pathways in AML tumors. SAR103168 showed potent anti
      tumor activity in SCID (severe combined immunodeficiency) mice bearing AML (KG1,
      EOL-1, Kasumi-1, CTV1) and chronic myeloid leukemia (CML) (K562) tumors. The
      combination of cytarabine and SAR103168 showed synergistic activity in AML and
      CML tumor models. These results highlight the therapeutic potential of SAR103168
      in myeloid leukemias and support the rationale for clinical investigations.

PMID- 23121565
TI  - Composition and antimicrobial activity of the skin peptidome of Russian brown
      frog Rana temporaria.
AB  - A nano-HPLC-ESI-OrbiTrap study involving HCD and ETD spectra has been carried out
      to clarify the composition of the skin peptidome of brown Russian frogs Rana
      temporaria. This approach allowed determinantion of 76 individual peptides,
      increasing 3-fold the identified portion of the peptidome in comparison to that
      obtained earlier with FTICR MS. A search for the new bradykinin related peptides
      (BRPs) was carried out by reconstructing mass chromatograms based on the ion
      current of characteristic b- and y-ions. Several peptides were reported in the
      secretion of R. temporaria for the first time. The overall antibacterial activity
      of the skin secretion in general and of one individual peptide (Brevinin 1Tb) was
      determined using PMEU Spectrion (Portable Microbe Enrichment Unit) technology.
      The inhibitory effects of these peptides on Staphylococcus aureus and Salmonella
      enterica Serovar typhimutium were equal in scale to that reported for some
      antibiotics.

PMID- 23121566
TI  - Emergency healthcare experiences of women living with intimate partner violence.
AB  - AIM AND OBJECTIVES: To explore healthcare experiences of Australian women living
      with intimate partner violence (IPV) and consider how these influence their
      understanding of IPV and sense of self. BACKGROUND: Despite international
      campaigns condemning violence against women, IPV remains a worldwide problem and
      recent Australian community attitudes demonstrate ongoing beliefs condemning
      women in abusive relationships. Women experiencing IPV are over-represented in
      healthcare-seeking populations; however, they are rarely identified as
      experiencing abuse and are often not provided care directed towards achieving
      ongoing safety. While women seek empathetic healthcare, disclosure of abuse often
      results in being judged negatively or blamed. DESIGN: A grounded theory study
      drawing on Clarke's (Sage Publications, London, 2005) analytic approach of
      situational analysis. METHODS: Semi-structured interviews conducted with seven
      women. Data was analysed using NVIVO 8 software within a Situational Analysis
      framework. RESULTS: Four major categories were identified: Accessing healthcare:
      challenges and barriers; Care women need vs. care women receive; Discourses of
      IPV and constructions of self; and Acknowledging IPV: moving on and re
      constructing self. Women faced significant challenges in accessing emergency
      healthcare and healthcare then often lacked empathy. Women created an
      understanding of self from a world dominated by an abusive partner and needed
      assistance re-labelling their experiences as IPV. Healthcare professionals who
      provided empathetic care were instrumental in assisting this process, enhancing
      women's abilities to explore options for limiting abuse and assisting them to
      enhance their self-efficacy and reconstruct a positive sense of self.
      CONCLUSIONS: Healthcare is one of the few avenues women living with IPV have to
      receive emotional and physical support. Healthcare that ignores psychosocial
      issues further damages women's sense of self. RELEVANCE TO CLINICAL PRACTICE:
      Women require timely information and empathetic support from healthcare
      professionals to assist them in understanding and labelling their experiences as
      IPV. This enhances women's ability to feel deserving of, and ideally achieve, a
      life without violence.

PMID- 23121568
TI  - Patient designs.

PMID- 23121567
TI  - Deciphering the epigenetic code: an overview of DNA methylation analysis methods.
AB  - SIGNIFICANCE: Methylation of cytosine in DNA is linked with gene regulation, and
      this has profound implications in development, normal biology, and disease
      conditions in many eukaryotic organisms. A wide range of methods and approaches
      exist for its identification, quantification, and mapping within the genome.
      While the earliest approaches were nonspecific and were at best useful for
      quantification of total methylated cytosines in the chunk of DNA, this field has
      seen considerable progress and development over the past decades. RECENT
      ADVANCES: Methods for DNA methylation analysis differ in their coverage and
      sensitivity, and the method of choice depends on the intended application and
      desired level of information. Potential results include global methyl cytosine
      content, degree of methylation at specific loci, or genome-wide methylation maps.
      Introduction of more advanced approaches to DNA methylation analysis, such as
      microarray platforms and massively parallel sequencing, has brought us closer to
      unveiling the whole methylome. CRITICAL ISSUES: Sensitive quantification of DNA
      methylation from degraded and minute quantities of DNA and high-throughput DNA
      methylation mapping of single cells still remain a challenge. FUTURE DIRECTIONS:
      Developments in DNA sequencing technologies as well as the methods for
      identification and mapping of 5-hydroxymethylcytosine are expected to augment our
      current understanding of epigenomics. Here we present an overview of
      methodologies available for DNA methylation analysis with special focus on recent
      developments in genome-wide and high-throughput methods. While the application
      focus relates to cancer research, the methods are equally relevant to broader
      issues of epigenetics and redox science in this special forum.

PMID- 23121569
TI  - "Hospital in the home": a lot's in a name.

PMID- 23121570
TI  - The Australasian Colorectal Cancer Family Registry.

PMID- 23121571
TI  - To ED or not to ED: a phone call will not answer.

PMID- 23121572
TI  - From the Australian Commission on Safety and Quality in Health Care. Guides for
      safe e-health systems in hospitals.

PMID- 23121573
TI  - Can we feel it in our waters? Antimicrobials in aquaculture.

PMID- 23121574
TI  - Exploring the economics of helicopter rescue in Australia.

PMID- 23121575
TI  - The medical workforce in 2025: what's in the numbers?

PMID- 23121576
TI  - Adverse effects of adult topical androgen use on children.

PMID- 23121577
TI  - Effect of false-positive screening mammograms on rescreening in Western
      Australia.

PMID- 23121578
TI  - Drug treatment for melanoma: progress, but who pays?

PMID- 23121579
TI  - Drug treatment for melanoma: progress, but who pays?

PMID- 23121580
TI  - Drug treatment for melanoma: progress, but who pays? Comment.

PMID- 23121581
TI  - Subsidised use of methylnaltrexone in Australia for palliative care.

PMID- 23121582
TI  - Liver cancer is the fastest increasing cause of cancer death in Australians.

PMID- 23121583
TI  - Eliminating childhood lead toxicity in Australia: a call to lower the
      intervention level.

PMID- 23121584
TI  - Recent developments in the diagnosis of Marfan syndrome and related disorders.
AB  - Marfan syndrome is a multisystem disorder of connective tissue that is inherited
      in an autosomal dominant fashion, and results from mutation of the FBN1 gene on
      human chromosome 15. There are a number of conditions of the connective tissue
      with a similar phenotype that can be confused with Marfan syndrome. Modifications
      of the diagnostic criteria have recently been published, facilitating the
      differentiation of Marfan syndrome from these conditions. It is still difficult
      to use modern genetic testing for diagnosis because Marfan syndrome can be caused
      by many different mutations in FBN1, a large gene with 65 coding segments, while
      mutations in other genes can cause overlapping phenotypes. Several clinical
      trials of drug therapy, including the antihypertensive drug losartan, are in
      progress.

PMID- 23121585
TI  - Appropriateness of healthdirect referrals to the emergency department compared
      with self-referrals and GP referrals.
AB  - OBJECTIVE: To assess the appropriateness of healthdirect referrals to the
      emergency department (ED) and compare these to self-referrals and general
      practitioner referrals. DESIGN AND SETTING: Prospective observational study
      conducted at the Royal Perth Hospital ED from August 2008 to April 2009, using
      the healthdirect database to cross check healthdirect advice with ED data.
      PATIENTS: Consecutive patients at triage, identified as healthdirect-referred,
      self-referred or GP-referred (720 patients per group). MAIN OUTCOME MEASURE:
      Appropriateness of referrals, using an a-priori definition. RESULTS: The
      healthdirect-referred patients were significantly younger than self-referred and
      GP-referred patients (mean age, 41.6 years v 45.5 years and 50.1 years,
      respectively; P < 0.01), more likely to be female (60.3% v 43.8% and 46.4%,
      respectively; P < 0.01) and more likely to attend the ED out of hours (64.0% v
      45.8% and 21.0%, respectively; P < 0.01). Self-referred patients had the highest
      acuity profile (P < 0.01). The proportions of referrals that were assessed as
      being appropriate were: healthdirect-referred, 72.9% (95% CI, 69.7%-76.2%); self
      referred, 73.8% (95% CI, 70.5%-77.0%); and GP-referred, 89.7% (95% CI, 87.5%
      91.9%). Of the 534 calls that could be traced back to the healthdirect database,
      280 (52.4%) represented patients who attended the ED despite a contrary
      recommendation. CONCLUSIONS: GP referrals had the highest level of
      appropriateness, and healthdirect- and self-referrals had similar levels of
      appropriateness. More than half the healthdirect-referred patients attended the
      ED despite a contrary recommendation, probably due to difficulty accessing after
      hours health services.

PMID- 23121586
TI  - Changes in smoking intensity among Aboriginal and Torres Strait Islander people,
      1994-2008.
AB  - OBJECTIVES: To describe smoking intensity among Indigenous Australians and any
      changes that occurred between 1994 and 2008. DESIGN, SETTING AND PARTICIPANTS:
      Analysis of data from two national cross-sectional household surveys conducted
      among Aboriginal and Torres Strait Islander people--the 1994 National Aboriginal
      and Torres Strait Islander Survey, and the 2008 National Aboriginal and Torres
      Strait Islander Social Survey, with 8565 and 7803 respondents aged 15 years and
      over, respectively. MAIN OUTCOME MEASURE: Self-reported number of cigarettes per
      day (CPD) smoked. RESULTS: In 2008, the mean number of CPD smoked by Indigenous
      smokers was 14.8 (95% CI, 14.1-15.4 CPD). The age-standardised proportion of
      Indigenous people who smoked more than 20 CPD declined from 17.3% in 1994 (95%
      CI, 15.8%-18.7%) to 9.4% in 2008 (95% CI, 8.4%-10.5%), a 45% relative reduction.
      The proportion of respondents who smoked 1-10 CPD increased from 16.8% (95% CI,
      15.1%-18.5%) to 21.6% (95% CI, 20.1%-23.2%). CONCLUSIONS: Together with reports
      of the decreasing prevalence of smoking among Indigenous people, this first
      report of a significant reduction in heavy smoking by Indigenous smokers is good
      news. Reducing smoking intensity and prevalence will lead to fewer deaths and
      less illness due to smoking. Reducing the number of heavy smokers will also
      assist smoking cessation among Indigenous people. These changes in smoking
      intensity occurred before the recent increase in attention to and investment in
      tobacco control in Indigenous communities, but at a time of significant
      mainstream anti-tobacco public health activity. Similar trends in smoking
      intensity have been reported in the total Australian population.

PMID- 23121587
TI  - Identifying and prioritising gaps in colorectal cancer trials research in
      Australia.
AB  - OBJECTIVES: To identify gaps in colorectal cancer clinical trials research in
      Australia and to suggest and prioritise trials to fill those gaps. DESIGN,
      SETTING AND PARTICIPANTS: Retrospective review of colorectal cancer trial
      activity from 1 January 2005 to 1 July 2011 in Australia and internationally,
      followed by a consensus meeting of consumers, health care professionals,
      researchers and funding agencies. MAIN OUTCOME MEASURES: Proportion of Phase III
      and randomised clinical trials in the areas of prevention, screening, surgery,
      adjuvant therapy, advanced disease and behavioural interventions, and priority
      areas of research identified by participants at the consensus meeting. RESULTS:
      The registry search identified 76 colorectal cancer clinical trials (all phases)
      registered in Australia from 1 January 2005 to 1 July 2011, of which 51 were
      Phase III or randomised, and 323 Phase III and randomised trials registered
      worldwide. In Australia, most trials were in advanced colorectal cancer (32),
      screening (10), and behavioural interventions (9). Worldwide, most Phase III or
      randomised trials were in advanced disease (94, 29.1%), surgery (64, 19.8%),
      behavioural interventions (38, 11.8%), and screening (30, 9.3%). At the consensus
      meeting, all participant groups emphasised the need for research in secondary
      prevention, screening, individualised treatments and follow-up care after
      treatment for colorectal cancer. CONCLUSIONS: There is a mismatch between the
      high proportion of registered trials in advanced colorectal cancer and the areas
      of priority identified. The development of specific trials in these priority
      areas depends on the availability of funding and the existence of plausible
      interventions likely to improve patient outcomes.

PMID- 23121588
TI  - A meta-analysis of "hospital in the home".
AB  - OBJECTIVE: To assess the effect of "hospital in the home" (HITH) services that
      significantly substitute for inhospital time on mortality, readmission rates,
      patient and carer satisfaction, and costs. DATA SOURCES: MEDLINE, Embase, Social
      Sciences Citation Index, CINAHL, EconLit, PsycINFO and the Cochrane Database of
      Systematic Reviews, from the earliest date in each database to 1 February 2012.
      STUDY SELECTION: Randomised controlled trials (RCTs) comparing HITH care with
      inhospital treatment for patients aged > 16 years. DATA EXTRACTION: Potentially
      relevant studies were reviewed independently by two assessors, and data were
      extracted using a collection template and checklist. DATA SYNTHESIS: 61 RCTs met
      the inclusion criteria. HITH care led to reduced mortality (odds ratio [OR],
      0.81; 95% CI, 0.69 to 0.95; P = 0.008; 42 RCTs with 6992 patients), readmission
      rates (OR, 0.75; 95% CI, 0.59 to 0.95; P = 0.02; 41 RCTs with 5372 patients) and
      cost (mean difference, -1567.11; 95% CI, -2069.53 to -1064.69;  P < 0.001; 11
      RCTs with 1215 patients). The number needed to treat at home to prevent one death
      was 50. No heterogeneity was observed for mortality data, but heterogeneity was
      observed for data relating to readmission rates and cost. Patient satisfaction
      was higher in HITH in 21 of 22 studies, and carer satisfaction was higher in and
      six of eight studies; carer burden was lower in eight of 11 studies, although not
      significantly (mean difference, 0.00; 95% CI, -0.19 to 0.19). CONCLUSION: HITH is
      associated with reductions in mortality, readmission rates and cost, and
      increases in patient and carer satisfaction, but no change in carer burden.

PMID- 23121589
TI  - Anaphylactic shock in a patient with mastocytosis.

PMID- 23121590
TI  - More than the sum of our parts.

PMID- 23121591
TI  - Where to die?

PMID- 23121592
TI  - First story--MJA Dr Eric Dark Creative Writing Prize.

PMID- 23121595
TI  - Relationship between performance validity testing, disability status, and somatic
      complaints in patients with fibromyalgia.
AB  - Fibromyalgia is a chronic pain-related disorder that typically includes cognitive
      complaints as well as non-specific somatic complaints, such as fatigue and sleep
      disturbance (Wolfe et al., 2010). Fibromyalgia has also been shown to be
      associated with a high rate of failure on performance validity testing (PVT),
      which has not been examined with respect to other self-reported symptoms that are
      now part of the diagnostic criteria for the disorder. We evaluated 85 patients
      with fibromyalgia who completed objective measures of pain, sleep, and fatigue
      along with symptom validity measures (Word Memory Test or Test of Memory
      Malingering and Reliable Digit Span). Three groups were formed based on effort
      testing: Two PVTs Failed, One PVT Failed, and No PVTs Failed. We also formed
      three groups based on disability status: On Disability, Applying for Disability,
      and Not on Disability. A total of 37% of the patients failed one or both PVTs.
      PVT group analyses were significant for daily pain, weekly pain, and sleep, but
      not fatigue. Disability status analyses were significant for daily pain, weekly
      pain, and fatigue, but not sleep. The implication of this study is that PVT
      performance and disability status are associated with exaggeration of non
      cognitive symptoms such as pain, sleep, and fatigue in persons with fibromyalgia.
      This study reinforces the importance of effort testing when working with medical
      populations.

PMID- 23121597
TI  - Extraction, separation, and intramolecular carbon isotope characterization of
      athabasca oil sands acids in environmental samples.
AB  - Here we report a novel approach to extract, isolate, and characterize high
      molecular weight organic acids found in the Athabasca oil sands region using
      preparative capillary gas chromatography (PCGC) followed by thermal
      conversion/elemental analysis-isotope ratio mass spectrometry (TC/EA-IRMS). A
      number of different "naphthenic acids" surrogate standards were analyzed as were
      samples from the bitumen-rich unprocessed McMurray Formation, oil sands process
      water, groundwater from monitoring wells, and surface water from the Athabasca
      River. The intramolecular carbon isotope signature generated by online pyrolysis
      (delta(13)C(pyr)) showed little variation (+/-0.60/00) within any given sample
      across a large range of mass fractions separated by PCGC. Oil sand, tailings
      ponds, and deep McMurray Formation groundwater were significantly heavier (up to
      ~90/00) compared to surface water and shallow groundwater samples, demonstrating
      the potential use of this technique in source apportionment studies.

PMID- 23121596
TI  - Convergences and divergences of diabetic patients' and healthcare professionals'
      opinions of care: a qualitative study.
AB  - OBJECTIVES: To investigate opinions' convergences and divergences of diabetic
      patients and health-care professionals on diabetes care and the development of a
      regional diabetes programme. BACKGROUND: Development and implementation of a
      regional diabetes programme. RESEARCH DESIGN: Qualitative study using focus
      groups to elicit diabetic patients' and health-care professionals' opinions,
      followed by content analysis. SETTING AND PARTICIPANTS: Eight focus groups: four
      focus groups with diabetic patients (n = 39) and four focus groups with various
      health-care professionals (n = 34) residing or practicing in the canton of Vaud,
      Switzerland, respectively. RESULTS: Perceived quality of diabetes care varied
      between individuals and types of participants. To improve quality, patients
      favoured a comprehensive follow-up while professionals suggested considering
      existing structures and trained professionals. All participants mentioned
      communication difficulties between professionals and were favouring teamwork. In
      addition, they described the role that patients should have in care and self
      management. Financial difficulties were also mentioned by both groups of
      participants. Finally, they were in favour of the development of a regional
      diabetes programme adapted to actors' needs. For patients indeed, such a
      programme would represent an opportunity to improve information and to have
      access to comprehensive care. For professionals, it would help the development of
      local networks and the reinforcement of existing tools and structures. DISCUSSION
      AND CONCLUSIONS: Acknowledging convergences and divergences of opinions of both
      diabetic patients and health-care professionals should help the further
      development of a programme adapted to users' needs, taking all stakeholders
      interests and priorities into consideration.

PMID- 23121598
TI  - A simple method of DNA isolation from jute (Corchorus olitorius) seed suitable
      for PCR-based detection of the pathogen Macrophomina phaseolina (Tassi) Goid.
AB  - A simple method was developed for isolating DNA from jute seed, which contains
      high amounts of mucilage and secondary metabolites, and a PCR protocol was
      standardized for detecting the seedborne pathogen Macrophomina phaseolina. The
      cetyl trimethyl ammonium bromide method was modified with increased salt
      concentration and a simple sodium acetate treatment to extract genomic as well as
      fungal DNA directly from infected jute seed. The Miniprep was evaluated along
      with five other methods of DNA isolation in terms of yield and quality of DNA and
      number of PCR positive samples. The Miniprep consistently recovered high amounts
      of DNA with good spectral qualities at A260/A280. The DNA isolated from jute seed
      was found suitable for PCR amplification. Macrophomina phaseolina could be
      detected by PCR from artificially inoculated as well as naturally infected jute
      seeds. The limit of PCR-based detection of M. phaseolina in jute seed was
      determined to be 0.62 * 10(-7) CFU g(-1) seed.

PMID- 23121599
TI  - Total synthesis and absolute configuration of curvularides A-E.
AB  - The first total synthesis of curvularides A-E, isolated from a culture broth of
      the endophytic fungus Curvularia geniculata, is described. The divergent total
      synthesis reported herein confirmed the absolute configurations of curvularides A
      E and supported that these natural products might be obtained from a common
      biosynthetic pathway. The key steps involved in the synthesis were the
      diastereoselective hydrogenation of exo-methylene-gamma-butyrolactone to alpha
      methyl-gamma-butyrolactone, Sharpless kinetic resolution, Sharpless asymmetric
      epoxidations, and intramolecular and intermolecular epoxide openings.

PMID- 23121600
TI  - Goals influence memory and imitation for dynamic human action in 36-month-old
      children.
AB  - Adults' memory for action is organized according to a hierarchy of goals. Little
      previous research has examined whether goals also play a crucial role in young
      children's memory for action, and particularly whether goal information is
      privileged over veridical sequential order information. The current experiment
      investigated 3-year-old children's (N = 40) memory for naturally occurring
      interleaved action sequences: Sequences in which an actor switched back and forth
      between carrying out actions related to two distinct goals. Such sequences
      allowed a test of whether children's action representations prioritize a goal
      interpretation over veridical sequential information. Children's memory for the
      action events was assessed by deferred imitation, 5-min after the demonstration
      had ceased. Results indicated that children's memory prioritizes goals over
      veridical sequential order - even to the extent that the actual sequential order
      is distorted in memory. These findings deepen our understanding of action
      processing and memory with implications for social-cognitive development.

PMID- 23121601
TI  - Intracellular calcium plays a critical role in the alcohol-mediated death of
      cerebellar granule neurons.
AB  - Alcohol is a potent neuroteratogen that can trigger neuronal death in the
      developing brain. However, the mechanism underlying this alcohol-induced neuronal
      death is not fully understood. Utilizing primary cultures of cerebellar granule
      neurons (CGN), we tested the hypothesis that the alcohol-induced increase in
      intracellular calcium [Ca(2+)](i) causes the death of CGN. Alcohol induced a dose
      dependent (200-800 mg/dL) neuronal death within 24 h. Ratiometric Ca(2+) imaging
      with Fura-2 revealed that alcohol causes a rapid (1-2 min), dose-dependent
      increase in [Ca(2+)](i), which persisted for the duration of the experiment (5 or
      7 min). The alcohol-induced increase in [Ca(2+)](i) was observed in Ca(2+) -free
      media, suggesting intracellular Ca(2+) release. Pre-treatment of CGN cultures
      with an inhibitor (2-APB) of the inositol-triphosphate receptor (IP(3) R), which
      regulates Ca(2+) release from the endoplasmic reticulum (ER), blocked both the
      alcohol-induced rise in [Ca(2+)](i) and the neuronal death caused by alcohol.
      Similarly, pre-treatment with BAPTA/AM, a Ca(2+) -chelator, also inhibited the
      alcohol-induced surge in [Ca(2+) ](i) and prevented neuronal death. In
      conclusion, alcohol disrupts [Ca(2+)](i) homeostasis in CGN by releasing Ca(2+)
      from intracellular stores, resulting in a sustained increase in [Ca(2+)](i). This
      sustained increase in [Ca(2+)](i) may be a key determinant in the mechanism
      underlying alcohol-induced neuronal death.

PMID- 23121602
TI  - Analysis of the light-sensitivity of the photoreceptor cells of the ataxia and
      male sterility (AMS) mouse, an Nna1 mutant.
AB  - We confirmed retinal degeneration in the ataxia and male sterility (AMS) mouse, a
      mutant of the Nna1 gene, and examined the photosensitivity of the photoreceptors
      to determine how closely related the intrinsic and extrinsic factors were in
      triggering photoreceptor cell death. The AMS mice reared in a dark environment
      did not show atrophy of the outer nuclear layer (ONL) before 4 weeks of age, but
      in the older mice, retinal atrophy progressed in the same manner as in the AMS
      mice housed under normal light conditions. Examining the sensitivity to
      intentional light stimulation revealed the atrophy of the AMS retina to be
      exacerbated by a weak light. After administering strong light irradiation,
      equally severe ONL atrophy occurred in both the wild-type and AMS mice. These
      results indicate that in addition to functional loss of Nna1, another injurious
      stimulation is necessary to trigger death signals in photoreceptor cells during
      the postnatal period, but the cells die gradually and autonomously in older age,
      and that the mutation makes the cells vulnerable to a weak light, but does not
      increase the number of cells sensitive to strong light stimulation. Thus, these
      two factors are mutually independent death triggers in AMS photoreceptor cells.

PMID- 23121603
TI  - Chromogenic in situ hybridization (CISH) to detect HER2 gene amplification in
      breast and gastric cancer: comparison with immunohistochemistry (IHC) and
      fluorescence in situ hybridization (FISH).
AB  - The chromogenic in situ hybridization (CISH) assay, designed to detect the
      amplification of the HER2 gene in formalin-fixed, paraffin-embedded (FFPE) breast
      cancer (BC) and gastric cancer (GC) tissue specimens, was evaluated in 125 FFPE
      BC cases and 198 FFPE GC cases for which the HER2 status had been predetermined
      using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH).
      In the 125 BC cases and the 198 gastric cases, we found a very good concordance
      (98.4% and 99.0%, respectively) between CISH and FISH. In particular, we
      evaluated the polysomy cases, as these cases often have ambiguous treatment
      options in clinical practice. The polysomy of chromosome 17 was defined as the
      presence of three or more CEP17 signals in at least 10% of the tumor cells. In
      the 50 BC cases and 54 GC cases displaying chromosome 17 polysomy, the
      concordance between FISH and CISH was 98.0% and 98.1%, respectively. These
      results indicate that CISH could provide an accurate and practical alternative to
      FISH for the clinical diagnosis of HER2 gene amplification in FFPE BC and FFPE GC
      samples.

PMID- 23121604
TI  - Expression of EZH2 in renal cell carcinoma as a novel prognostic marker.
AB  - Enhancer of zeste homolog 2 (EZH2) is a member of the Polycomb group proteins and
      a part of Polycomb repressive complex 2. EZH2 is important for transcriptional
      regulation through nucleosome modification and interaction with other
      transcription factors. Particularly, aberration of EZH2 has been implicated in
      oncogenesis and progression of various neoplasms. The objective of this study was
      to evaluate EZH2 expression in renal cell carcinoma (RCC), especially clear cell
      RCC (CRCC) and correlate the expression with prognostic factors. EZH2 expression
      was determined by immunohistochemical staining with additional Western blotting.
      High expression of EZH2 was significantly correlated with higher pT stage or more
      frequent distant metastases (P= 0.001 and 0.024, respectively). Survival analyses
      displayed that patients with high EZH2 expression had a significantly shorter
      disease-free survival than those with low expression (P= 0.019). High expression
      of EZH2 tended to reduce the overall survival, however, differences did not reach
      statistical significance (P= 0.066). From our results, we propose that EZH2 is a
      useful prognostic marker for aggressive behavior of CRCC and may be applicable as
      a therapeutic target molecule.

PMID- 23121605
TI  - Expression of ERG oncoprotein is associated with a less aggressive tumor
      phenotype in Japanese prostate cancer patients.
AB  - To investigate and characterize ERG oncoprotein expression in Japanese patients
      with prostate cancer (PCa), we evaluated 92 index tumors from Japanese patients
      who had undergone radical prostatectomy for PCa, using an antibody-based
      detection method to determine ERG expression. Expression status was compared with
      clinicopathological findings including patient age, body mass index and
      preoperative prostate-specific antigen (PSA) levels, specimen Gleason score,
      pathological stage, positive surgical margin, size of index tumor, prostatic
      volume, zonal origin of index tumor and biochemical failure. Overall, ERG protein
      was expressed in 16.3% (15/92) of the index tumors, but not in benign glands.
      Younger patient age, lower Gleason score and negative surgical margins were found
      to be independently associated with its expression in the multivariate analysis
      (P= 0.015, 0.003 and 0.038, respectively). ERG expression was not associated with
      biochemical failure. Though not statistically significant, ERG expression was
      more frequently observed in peripheral zone than in transition zone cancers
      (28.2% vs 10%, respectively). In conclusion, ERG protein was less frequently
      expressed in this Japanese PCa cohort compared with Western reports. ERG
      expression was associated with a less aggressive tumor phenotype, and its
      biological significance needs to be further investigated.

PMID- 23121606
TI  - Malignant melanoma arising in a plaque-type blue nevus.
AB  - Blue nevus is a type of dermal melanocytosis and has a variety of
      clinicopathological characteristics. A few particular variants are generally
      accepted as discrete clinicopathological entities. Plaque-type blue nevus (PTBN)
      is one of the variants of blue nevus. PTBN presents at birth or arises in early
      childhood, and shows a combination of features found in common blue nevus and
      cellular blue nevus. In this report, we describe a malignant melanoma arising in
      association with a PTBN in a 65-year-old male. The tumor appeared as a well
      circumscribed but partially infiltrative upper-abdominal mass, and was heavily
      pigmented and consisted of a spindle or epithelioid highly cellular component
      with mitotic figures and tumor necroses. In the skin around the tumor, multiple
      pigmented lesions were scattered around the trunk, and these had been recognized
      since childhood. Histologically, skin lesions showed sparse and wide distribution
      of the dendritic melanocytes with dense melanin pigments and melanophages between
      the collagen bundles from the reticular dermis to the abdominal skeletal muscle.
      We also discuss the histological features and clinical course in our patient in
      context with previous related literature.

PMID- 23121607
TI  - The recurrence of malignant pleural mesothelioma 14 years after extrapleural
      pneumonectomy: possible histological transformation.
AB  - A 56-year-old man underwent extrapleural pneumonectomy for malignant pleural
      mesothelioma (MPM). The histological diagnosis was epithelioid mesothelioma with
      T2N0M0, and no sarcomatoid component was observed. Subsequently, 14 years after
      complete resection, screening computed tomography detected a rapidly growing
      right thoracic mass, which was diagnosed as a recurrence of MPM on resection.
      However, it was composed of both epithelioid (50%) and sarcomatoid (50%)
      components, suggesting possible histological transformation. Although there have
      been some previous reports on the recurrence of MPM, to the best of our
      knowledge, this is the first clinical case which indicated that histological
      transformation of MPM might occur.

PMID- 23121608
TI  - A large coronary aneurysm and its probable precursor lesions in a patient with
      autosomal dominant polycystic kidney disease: an implication for the process of
      aneurysmogenesis.
AB  - Coronary artery aneurysms are rare complications of autosomal dominant polycystic
      kidney disease (ADPKD), and their pathogenesis remains poorly understood. We
      report an autopsy case of a 64-year-old ADPKD patient with an asymptomatic, large
      (4 cm in diameter) saccular aneurysm arising from the left circumflex (LCX)
      branch of the coronary artery with only mild atherosclerotic changes. Autopsy
      also revealed small, focal defects of media with or without microaneurysm
      formation in the LCX, mesenteric and renal arteries, and a fibromuscular
      dysplasia-like lesion with microaneurysm in the common iliac artery. Since
      polycystin-1 and -2 are expressed in arterial smooth-muscle cells, these findings
      imply that abnormal polycystin expression in ADPKD initially causes the focal
      medial defects, some of which might later progress to microaneurysms and then
      overt aneurysms. To the best of our knowledge, this is the first description of
      the pathologic findings of an ADPKD-associated coronary aneurysm and its probable
      precursor lesions in arteries.

PMID- 23121609
TI  - Plasmablastic lymphoma of the stomach in an HIV-negative patient.
AB  - Plasmablastic lymphoma (PBL) is a rare B-cell neoplasm with an aggressive
      clinical behavior that predominantly occurs in the oral cavity of human
      immunodeficiency virus (HIV)-positive patients. However, it has recently been
      recognized that PBLs can also affect individuals without HIV infection, and
      suggested that these neoplasms show different clinicopathological characteristics
      between HIV-positive and -negative patients. Herein we describe a case of gastric
      PBL in a female HIV-negative patient. The tumor was composed of a diffuse and
      cohesive proliferation of large neoplastic cells, which resembled immunoblasts or
      plasmablasts with a starry sky appearance. Immunophenotypically, the neoplastic
      cells were diffusely positive for CD138, MUM1, IgM, and BOB-1, and negative for
      CK, LCA, CD3, CD20, CD79a, Pax5, kappa, lambda, CD30, ALK, S-100, HMB-45, MPO,
      and HHV-8. The MIB-1 index was nearly 100%. Epstein-Barr virus-encoded RNA in
      situ hybridization was negative. A monoclonal immunoglobulin heavy chain gene
      rearrangement was detected in polymerase chain reaction (PCR) and heteroduplex
      analyses. A combination of PCR-based analysis of immunoglobulin gene
      rearrangement and immunohistochemistry can be useful to substantiate the
      diagnosis by utilizing routine paraffin-embedded tissue sections, because PBL in
      the setting of extra-oral localization and immunocompetence is a diagnostic
      challenge, given its rarity, morphology, and absence of CD20 expression.

PMID- 23121610
TI  - A stone-like ovarian dermoid cyst in the Douglas' Pouch of an elderly woman.

PMID- 23121611
TI  - Chronic inflammation on initial benign prostate biopsy is a negative predictor of
      subsequent cancer detection.

PMID- 23121612
TI  - Peri-operative intravenous administration of magnesium sulphate and postoperative
      pain: a meta-analysis.
AB  - Intravenous magnesium has been reported to improve postoperative pain; however,
      the evidence is inconsistent. The objective of this quantitative systematic
      review is to evaluate whether or not the peri-operative administration of
      intravenous magnesium can reduce postoperative pain. Twenty-five trials comparing
      magnesium with placebo were identified. Independent of the mode of administration
      (bolus or continuous infusion), peri-operative magnesium reduced cumulative
      intravenous morphine consumption by 24.4% (mean difference: 7.6 mg, 95% CI -9.5
      to -5.8 mg; p < 0.00001) at 24 h postoperatively. Numeric pain scores at rest and
      on movement at 24 h postoperatively were reduced by 4.2 (95% CI -6.3 to -2.1; p <
      0.0001) and 9.2 (95% CI -16.1 to -2.3; p = 0.009) out of 100, respectively. We
      conclude that peri-operative intravenous magnesium reduces opioid consumption,
      and to a lesser extent, pain scores, in the first 24 h postoperatively, without
      any reported serious adverse effects.

PMID- 23121613
TI  - Bacterial pathogen phytosensing in transgenic tobacco and Arabidopsis plants.
AB  - Plants are subject to attack by a wide range of phytopathogens. Current pathogen
      detection methods and technologies are largely constrained to those occurring
      post-symptomatically. Recent efforts were made to generate plant sentinels
      (phytosensors) that can be used for sensing and reporting pathogen contamination
      in crops. Engineered phytosensors indicating the presence of plant pathogens as
      early-warning sentinels potentially have tremendous utility as wide-area
      detectors. We previously showed that synthetic promoters containing pathogen
      and/or defence signalling inducible cis-acting regulatory elements (RE) fused to
      a fluorescent protein (FP) reporter could detect phytopathogenic bacteria in a
      transient phytosensing system. Here, we further advanced this phytosensing system
      by developing stable transgenic tobacco and Arabidopsis plants containing
      candidate constructs. The inducibility of each synthetic promoter was examined in
      response to biotic (bacterial pathogens) or chemical (plant signal molecules
      salicylic acid, ethylene and methyl jasmonate) treatments using stably transgenic
      plants. The treated plants were visualized using epifluorescence microscopy and
      quantified using spectrofluorometry for FP synthesis upon induction. Time-course
      analyses of FP synthesis showed that both transgenic tobacco and Arabidopsis
      plants were capable to respond in predictable ways to pathogen and chemical
      treatments. These results provide insights into the potential applications of
      transgenic plants as phytosensors and the implementation of emerging technologies
      for monitoring plant disease outbreaks in agricultural fields.

PMID- 23121614
TI  - Risk factors for porphyria cutanea tarda -the iron/HFE connection.

PMID- 23121615
TI  - Evaluation of the ASPIRANT trial.
AB  - Several pathophysiological, clinical, and therapeutic features of resistant
      hypertension are far from being clearly defined. This is the case also for the
      efficacy of aldosterone receptor antagonists as an add-on treatment of resistant
      hypertension. The Addition of Spironolactone in Patients with Resistant Arterial
      Hypertension (ASPIRANT) trial evaluated, with a double-blind, placebo-controlled
      design, the effects of low-dose (25 mg/day) spironolactone as compared with
      placebo on clinic and ambulatory blood pressure in 117 resistant hypertensive
      obese patients, already under treatment with at least four antihypertensive
      drugs. The primary study endpoint was the achievement of a statistically
      significant difference in the systo-diastolic blood pressure reduction during the
      daytime period between the spironolactone-treated and the placebo-treated group.
      The results show that aldosterone blockade was associated with a significant
      reduction in clinic, 24-h and daytime systolic (but not in diastolic) blood
      pressure as compared with the placebo-treated group, the systo-diastolic blood
      pressure difference between the two treatment regimens amounting to 5.4/1.0 mmHg.
      Although a number of limitations weaken some of the study conclusions, ASPIRANT
      trial provides the first controlled evidence on the blood pressure-lowering
      effects of low-dose spironolactone in resistant hypertensive patients.

PMID- 23121616
TI  - A novel mass spectrometry-based method for determining insulin-like growth factor
      1: assessment in a cohort of subjects with newly diagnosed acromegaly.
AB  - OBJECTIVE: To develop an alternative method to immunoassay for the quantitative
      analysis of insulin-like growth factor 1 (IGF-1) using a mass spectrometry (MS)
      based approach. STUDY DESIGN AND PATIENTS: A stable isotope dilution Ultra High
      Performance Liquid Chromatography tandem MS (uHPLC-MS/MS)-based method for the
      quantification of IGF-1 was developed. The method employed Selected Reaction
      Monitoring (SRM) of two tryptic peptides derived from IGF-1, and utilised solid
      phase extraction for enrichment of the peptide fraction containing IGF-1 rather
      than immunocapture, so was less susceptible to assay interference. Plasma samples
      from 25 consecutive unselected patients with newly diagnosed acromegaly,
      collected both before and after 24 weeks of primary medical therapy with
      Lanreotide Autogel((r)), were analysed by a widely used commercial immunoassay
      (Siemens Immulite 2000((r))) and by uHPLC-MS/MS. RESULTS: The uHPLC-MS/MS method
      showed good correlation with the immunoassay over a wide range of IGF-1
      concentrations. The Passing and Bablock regression was: uHPLC-MS/MS (nmol/l) =
      1.37 (95% confidence interval: 1.26-1.46) * immunoassay (nmol/l) + 3.14 (95%
      confidence interval: -2.71 to 10.32). Six patients had discordant growth hormone
      (GH) and IGF-1 levels following primary medical therapy, and in all six the
      immunoassay and uHPLC-MS/MS platforms returned comparable results. The method was
      not affected by concentrations of IGFBP3 up to 12,500 ng/ml. CONCLUSIONS: uHPLC
      MS/MS offers an independent method for determining/validating IGF-1 in subjects
      with acromegaly. Further studies, including the establishment of age- and sex
      matched reference ranges and calibration to the new International IGF-1 standard
      IS 02/254, are now required to allow its introduction in to routine clinical use.

PMID- 23121617
TI  - Blunted proarrhythmic effect of nicorandil in a Langendorff-perfused phase-2
      myocardial infarction rabbit model.
AB  - BACKGROUND: Nicorandil (a K(ATP) opener) administration is reported to reduce
      ventricular arrhythmias 4.8 +/- 2.2 hours after myocardial infarction (MI). The
      electrophysiological changes and the effects on dynamic factors and dynamically
      induced spatially discordant alternans by nicorandil during phase-2 MI are
      unclear. METHODS: Simultaneous voltage and intracellular Ca(2+) (Ca(i)) optical
      mapping was performed in nine Langendorff-perfused hearts 4-5 hours after
      coronary artery ligation and nine control hearts. Action potential duration (APD)
      restitution was constructed and arrhythmogenic alternans was induced by dynamic
      pacing. Western blot studies (Kir6.1 and Kir6.2) were performed in six more
      hearts for both groups. Nicorandil (100 MUM) was administered after baseline
      studies. RESULTS: Phase-2 MI hearts showed longer APD, slower conduction velocity
      (CV), and higher ventricular fibrillation (VF) inducibility than the control
      hearts. Nicorandil shortened and restored APD without significant arrhythmogenic
      effects, and also increased the rate of Ca(i) reuptake and flattened CV
      restitution to suppress spatially discordant alternans, which might account for a
      tendency toward higher VF threshold with nicorandil infusion in phase-2 MI
      hearts. Immunoblotting studies showed significant down-regulation of K(ATP)
      protein expression, which was functionally correlated to the blunted APD
      shortening response to nicorandil. CONCLUSIONS: K(ATP) expression is down
      regulated in phase-2 MI hearts. Nicorandil restores APD, increases the rate of
      Ca(i) reuptake, and flattens CV restitution to suppress spatially discordant
      alternans induction, which ameliorates its proarrhythmic effects during phase-2
      MI.

PMID- 23121620
TI  - Photoluminescence switching with changes in the coordination number and
      coordinating volatile organic compounds in tetracyanidonitridorhenium(V) and 
      technetium(V) complexes.
AB  - Six-coordinate distorted octahedral tetracyanidonitridorhenium(V) and 
      technetium(V) complexes with a volatile organic compound (VOC) coordinating at
      the trans position of a nitrido ligand, (PPh4)2[MN(CN)4L] (M = Re, L = MeOH,
      EtOH, acetone, or MeCN; M = Tc, L = MeOH), and five-coordinate square-pyramidal
      tetracyanidonitrido complexes without an axial ligand, (PPh4)2[MN(CN)4] (M = Re
      or Tc), were synthesized and characterized. Single-crystal X-ray structural
      analysis was carried out for (PPh4)2[MN(CN)4L] (M = Re, L = MeOH, EtOH, or
      acetone; M = Tc, L = MeOH) and (PPh4)2[ReN(CN)4]. All complexes studied showed
      photoluminescence in the solid state at room temperature. Reversible luminescence
      switching between six- and five-coordinate rhenium(V) complexes and between the
      relevant six-coordinate rhenium(V) complexes except that between the MeCN and
      acetone complexes was achieved by exposing them to VOC vapor in the solid state
      at room temperature. Luminescence changes were observed from the five-coordinate
      technetium(V) complexes in a MeOH vapor atmosphere in the solid state. In
      contrast, no vapochromic luminescence was observed from the five- and six
      coordinate complexes in an acetone vapor atmosphere. 

PMID- 23121618
TI  - Cannabidiolic acid prevents vomiting in Suncus murinus and nausea-induced
      behaviour in rats by enhancing 5-HT1A receptor activation.
AB  - BACKGROUND AND PURPOSE: To evaluate the ability of cannabidiolic acid (CBDA) to
      reduce nausea and vomiting and enhance 5-HT(1A) receptor activation in animal
      models. EXPERIMENTAL APPROACH: We investigated the effect of CBDA on (i) lithium
      chloride (LiCl)-induced conditioned gaping to a flavour (nausea-induced
      behaviour) or a context (model of anticipatory nausea) in rats; (ii) saccharin
      palatability in rats; (iii) motion-, LiCl- or cisplatin-induced vomiting in house
      musk shrews (Suncus murinus); and (iv) rat brainstem 5-HT(1A) receptor activation
      by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and mouse whole brain CB(1)
      receptor activation by CP55940, using [35S]GTPgammaS-binding assays. KEY RESULTS:
      In shrews, CBDA (0.1 and/or 0.5 mg.kg-1 i.p.) reduced toxin- and motion-induced
      vomiting, and increased the onset latency of the first motion-induced emetic
      episode. In rats, CBDA (0.01 and 0.1 mg.kg-1 i.p.) suppressed LiCl- and context
      induced conditioned gaping, effects that were blocked by the 5-HT(1A) receptor
      antagonist, WAY100635 (0.1 mg.kg-1 i.p.), and, at 0.01 mg.kg-1 i.p., enhanced
      saccharin palatability. CBDA-induced suppression of LiCl-induced conditioned
      gaping was unaffected by the CB1 receptor antagonist, SR141716A (1 mg.kg-1 i.p.).
      In vitro, CBDA (0.1-100 nM) increased the E(max) of 8-OH-DPAT. CONCLUSIONS AND
      IMPLICATIONS: Compared with cannabidiol, CBDA displays significantly greater
      potency at inhibiting vomiting in shrews and nausea in rats, and at enhancing 5
      HT(1A) receptor activation, an action that accounts for its ability to attenuate
      conditioned gaping in rats. Consequently, CBDA shows promise as a treatment for
      nausea and vomiting, including anticipatory nausea for which no specific therapy
      is currently available.

PMID- 23121619
TI  - Advances in the biology and therapy of chronic myeloid leukemia: proceedings from
      the 6th Post-ASH International Chronic Myeloid Leukemia and Myeloproliferative
      Neoplasms Workshop.
AB  - Following the 53rd annual meeting of the American Society of Hematology (ASH) in
      San Diego in December 2011, a group of clinical and laboratory investigators
      convened for the 6th Post-ASH International Workshop on Chronic Myeloid Leukemia
      (CML) and Myeloproliferative Neoplasms (MPN). The Workshop took place on 13-14
      December at the Estancia, La Jolla, California, USA. This report summarizes the
      most recent advances in the biology and therapy of CML that were presented at the
      ASH meeting and discussed at the Workshop. Preclinical studies focused on the CML
      stem cell and its niche, and on early results of deep sequencing of CML genomes.
      Clinical advances include updates on second- and third-generation tyrosine kinase
      inhibitors (TKIs), molecular monitoring, TKI discontinuation studies and new
      therapeutic agents. A report summarizing the pertinent advances in MPN has been
      published separately.

PMID- 23121621
TI  - Lycojaponicumins D and E: two new alkaloids from Lycopodium japonicum.
AB  - Two new alkaloids, lycojaponicumins D (1) and E (2), were isolated from the club
      moss Lycopodium japonicum. Their structures were elucidated by spectroscopic
      methods, calculated ECD, CD experiments and X-ray diffraction analysis.
      Lycojaponicumin D (1) possesses an unprecedented 5/7/6/6 tetracyclic skeleton
      formed by an unusual C3-C13 linkage, which is first reported in Lycopodium
      alkaloids. The plausible biogenetic pathway of 1 is proposed.

PMID- 23121623
TI  - Analysis of microbial diversity on deli slicers using polymerase chain reaction
      and denaturing gradient gel electrophoresis technologies.
AB  - Cross-contamination of pathogenic and spoilage bacteria from food-contact
      surfaces to food products is a serious public health issue. Bacteria may survive
      and attach to food-contact surfaces by residual food components and/or background
      bacteria which may subsequently transfer to other food products. Deli slicers,
      generally used for slicing ready-to-eat products, can serve as potential sources
      for considerable bacterial transfer. The objective of this study was to assess
      the extent and distribution of microbial diversity of deli slicers by
      identification of pathogenic and background bacteria. Slicer-swab samples were
      collected from restaurants in Arkansas and Texas in the United States. Ten
      surface areas for each slicer were swabbed using sterile sponges. Denaturing
      gradient gel electrophoresis (DGGE) was applied to investigate the fingerprint of
      samples, and each band was further identified by sequence analysis. Pseudomonads
      were identified as the dominant bacteria followed by Enterobacteriaceae family,
      and lactic acid bacteria such as Lactococcus lactis and Streptococcus
      thermophilus were also found. Bacterial distribution was similar for all surface
      areas, while the blade guard exhibited the greatest diversity. This study
      provides a profile of the microbial ecology of slicers using DGGE to develop more
      specific sanitation practices and to reduce cross-contamination during slicing.

PMID- 23121624
TI  - Quantitative imaging of gold and silver nanoparticles in single eukaryotic cells
      by laser ablation ICP-MS.
AB  - Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) was
      utilized for spatially resolved bioimaging of the distribution of silver and gold
      nanoparticles in individual fibroblast cells upon different incubation
      experiments. High spatial resolution was achieved by optimization of scan speed,
      ablation frequency, and laser energy. Nanoparticles are visualized with respect
      to cellular substructures and are found to accumulate in the perinuclear region
      with increasing incubation time. On the basis of matrix-matched calibration, we
      developed a method for quantification of the number of metal nanoparticles at the
      single-cell level. The results provide insight into nanoparticle/cell
      interactions and have implications for the development of analytical methods in
      tissue diagnostics and therapeutics.

PMID- 23121622
TI  - Selenocysteine in thiol/disulfide-like exchange reactions.
AB  - SIGNIFICANCE: Among trace elements used as cofactors in enzymes, selenium is
      unique in that it is incorporated into proteins co-translationally in the form of
      an amino acid, selenocysteine (Sec). Sec differs from cysteine (Cys) by only one
      atom (selenium versus sulfur), yet this switch dramatically influences important
      aspects of enzyme reactivity. RECENT ADVANCES: The main focus of this review is
      an updated and critical discussion on how Sec might be used to accelerate
      thiol/disulfide-like exchange reactions in natural selenoenzymes, compared with
      their Cys-containing homologs. CRITICAL ISSUES: We discuss in detail three major
      aspects associated with thiol/disulfide exchange reactions: (i) nucleophilicity
      of the attacking thiolate (or selenolate); (ii) electrophilicity of the center
      sulfur (or selenium) atom; and (iii) stability of the leaving group (sulfur or
      selenium). In all these cases, we analyze the benefits that selenium might
      provide in these types of reactions. FUTURE DIRECTIONS: It is the biological
      thiol oxidoreductase-like function that benefits from the use of Sec, since Sec
      functions to chemically accelerate the rate of these reactions. We review various
      hypotheses that could help explain why Sec is used in enzymes, particularly with
      regard to competitive chemical advantages provided by the presence of the
      selenium atom in enzymes. Ultimately, these chemical advantages must be connected
      to biological functions of Sec.

PMID- 23121625
TI  - Fecal microbiota transplantation for fulminant Clostridium difficile infection in
      an allogeneic stem cell transplant patient.
AB  - We present a case of severe Clostridium difficile infection (CDI) in a non
      neutropenic allogeneic hematopoietic stem cell transplant recipient who was
      treated successfully with fecal microbiota therapy after standard pharmacologic
      therapy had failed. Following naso-jejunal instillation of donor stool, the
      patient's symptoms resolved within 48 h. Bowel resection was averted. This is the
      first case in the literature, to our knowledge, to describe fecal microbiota
      therapy in a profoundly immunocompromised host with severe CDI. We propose that
      fecal microbiota therapy be considered as a therapeutic option in
      immunosuppressed patients with refractory severe CDI.

PMID- 23121626
TI  - Highly robust, recyclable displacement assay for mercuric ions in aqueous
      solutions and living cells.
AB  - We designed a recyclable Hg(2+) probe based on Rhodamine B isothiocyanate (RBITC)
      poly(ethylene glycol) (PEG)-comodified gold nanoparticles (AuNPs) with excellent
      robustness, selectivity, and sensitivity. On the basis of a rational design, only
      Hg(2+) can displace RBITC from the AuNP surfaces, resulting in a remarkable
      enhancement of RBITC fluorescence initially quenched by AuNPs. To maintain
      stability and monodispersity of AuNPs in real samples, thiol-terminated PEG was
      employed to bind with the remaining active sites of AuNPs. Besides, this
      displacement assay can be regenerated by resupplying free RBITC into the AuNPs
      solutions that were already used for detecting Hg(2+). Importantly, the detection
      limit of this assay for Hg(2+) (2.3 nM) was lower than the maximum limits guided
      by the United States Environmental Protection Agency as well as that permitted by
      the World Health Organization. The efficiency of this probe was demonstrated in
      monitoring Hg(2+) in complex samples such as river water and living cells.

PMID- 23121631
TI  - A response to: Self-reported and actual hepatitis C virus infection status.

PMID- 23121632
TI  - Fructose impacts on gut microbiota and obesity by A. N. Payne et al.

PMID- 23121634
TI  - Development and validation of an instrument to measure the burden experienced by
      community health volunteers.
AB  - AIMS AND OBJECTIVES: To develop and validate a scale to measure the burden
      experienced by community health volunteers. BACKGROUND: Research demonstrates the
      burden experienced by informal carers is substantial. There is no available
      information about the burden placed on community health volunteers, nor is there
      a scale developed for the purpose of measuring their burden. DESIGN: An
      instrument development and psychometric analysis study was undertaken. METHODS:
      Exploratory principal component factor analysis was applied to investigate the
      internal structure of the new scale. RESULTS: The initial item pool derived from
      literature review and experts resulted in 44 items linked to volunteer burden.
      The final scale includes 20 items with a content validity index of 0.86 and
      Cronbach's alpha for test (0.82) and retest (0.77). The reliability coefficient
      of the test-retest results was 0.63 [95%-confidence interval = (0.44, 0.77)].
      Principal component analysis identified five underlying factors: Factor 1 items
      are related to personal and family matters; factor 2 items are related to
      administrative issues; factor 3 items concern the community support; factor 4
      items are related to organisational matters; and factor 5 items concern issues of
      adequate health promotion delivery. CONCLUSION: The 20 item instrument designed
      to measure the burden on community health volunteers in Taiwan showed good
      internal consistency, content validity and construct validity. The findings infer
      that the scale may be an effective measure of the burden experienced by community
      health volunteers. Further testing of this scale within other countries that make
      use of community health volunteers is required to confirm the results. RELEVANCE
      TO CLINICAL PRACTICE: As volunteers play an important role in supporting the work
      of community health nurses, the new scale provides a means for nurses to assess
      volunteers' level of burden and develop interventions as required.

PMID- 23121635
TI  - The analgesic efficacy and safety of neuraxial magnesium sulphate: a quantitative
      review.
AB  - Eighteen published trials have examined the use of neuraxial magnesium as a peri
      operative adjunctive analgesic since 2002, with encouraging results. However,
      concurrent animal studies have reported clinical and histological evidence of
      neurological complications with similar weight-adjusted doses. The objectives of
      this quantitative systematic review were to assess both the analgesic efficacy
      and the safety of neuraxial magnesium. Eighteen trials comparing magnesium with
      placebo were identified. The time to first analgesic request increased by 11.1%
      after intrathecal magnesium administration (mean difference: 39.6 min; 95% CI
      16.3-63.0 min; p = 0.0009), and by 72.2% after epidural administration (mean
      difference: 109.5 min; 95% CI 19.6-199.3 min; p = 0.02) with doses of between 50
      and 100 mg. Four trials monitored for neurological complications: of the 140
      patients included, only a 4-day persistent headache was recorded. Despite
      promising peri-operative analgesic effect, the risk of neurological complications
      resulting from neuraxial magnesium has not yet been adequately defined.

PMID- 23121636
TI  - Reply 1.

PMID- 23121639
TI  - Visual processing speed in old age.
AB  - Mental speed is a common concept in theories of cognitive aging, but it is
      difficult to get measures of the speed of a particular psychological process that
      are not confounded by the speed of other processes. We used Bundesen's (1990)
      Theory of Visual Attention (TVA) to obtain specific estimates of processing speed
      in the visual system controlled for the influence of response latency and
      individual variations of the perception threshold. A total of 33 non-demented old
      people (69-87 years) were tested for the ability to recognize briefly presented
      letters. Performance was analyzed by the TVA model. Visual processing speed
      decreased approximately linearly with age and was on average halved from 70 to 85
      years. Less dramatic aging effects were found for the perception threshold and
      the visual apprehension span. In the visual domain, cognitive aging seems to be
      most clearly related to reductions in processing speed.

PMID- 23121637
TI  - Chronic clozapine reduces rat brain arachidonic acid metabolism by reducing
      plasma arachidonic acid availability.
AB  - Chronic administration of mood stabilizers to rats down-regulates the brain
      arachidonic acid (AA) cascade. This down-regulation may explain their efficacy
      against bipolar disorder (BD), in which brain AA cascade markers are elevated.
      The atypical antipsychotics, olanzapine (OLZ) and clozapine (CLZ), also act
      against BD. When given to rats, both reduce brain cyclooxygenase activity and
      prostaglandin E(2) concentration; OLZ also reduces rat plasma unesterified and
      esterified AA concentrations, and AA incorporation and turnover in brain
      phospholipid. To test whether CLZ produces similar changes, we used our in vivo
      fatty acid method in rats given 10 mg/kg/day i.p. CLZ, or vehicle, for 30 days;
      or 1 day after CLZ washout. [1-(14) C]AA was infused intravenously for 5 min,
      arterial plasma was collected and high-energy microwaved brain was analyzed. CLZ
      increased incorporation coefficients ki * and decreased [corrected] rates J(in,i)
      of plasma unesterified AA into brain phospholipids. [corrected]. These effects
      disappeared after washout. Thus, CLZ and OLZ similarly down-regulated kinetics
      and cyclooxygenase expression of the brain AA cascade, likely by reducing plasma
      unesterified AA availability. Atypical antipsychotics and mood stabilizers may be
      therapeutic in BD by down-regulating, indirectly or directly respectively, the
      elevated brain AA cascade of that disease.

PMID- 23121640
TI  - Design and synthesis of lipids for the fabrication of functional lipidic cubic
      phase biomaterials.
AB  - A series of novel lipids with designed functionalities were synthesized. These
      lipids are based on conjugation of alpha-amino acids and their esters, cationic,
      anionic, neutral, and photochromic moieties to the lipophilic 9-cis octadecenyl
      chains by amide, ester, thioester, or amine bonds. Because of the plasticity of
      lipidic cubic phases, it is envisaged that when mixed with monooleoyl-rac
      glycerol (monoolein, MO) and water at appropriate proportions, they would
      assemble to form bicontinuous lipidic cubic phases (LCPs) that exhibit the well
      known material properties of LCPs such as phase stability, optical transparency,
      and chemical permeability. Moreover, due to the nature and position of the
      functionality at the headgroup region, we envision them to perform as functional
      materials by design.

PMID- 23121638
TI  - Macrophage-derived Hedgehog ligands promotes fibrogenic and angiogenic responses
      in human schistosomiasis mansoni.
AB  - BACKGROUND: Schistosomiasis mansoni is a major cause of portal fibrosis and
      portal hypertension. The Hedgehog pathway regulates fibrogenic repair in some
      types of liver injury. AIMS: Determine if Hedgehog pathway activation occurs
      during fibrosis progression in schistosomiasis and to determine if macrophage
      related mechanisms are involved. METHODS: Immunohistochemistry was used to
      characterize the cells that generate and respond to Hedgehog ligands in 28 liver
      biopsies from patients with different grades of schistosomiasis fibrosis staged
      by ultrasound. Cultured macrophages (RAW264.7 and primary rat Kupffer cells) and
      primary rat liver sinusoidal endothelial cells (LSEC) were treated with
      schistosome egg antigen (SEA) and evaluated using qRT-PCR. Inhibition of the
      Hedgehog pathway was used to investigate its role in alternative activation of
      macrophages (M2) and vascular tube formation. RESULTS: Patients with
      schistosomiasis expressed more ligands (Shh and Ihh) and target genes (Patched
      and Gli2) than healthy individuals. Activated LSEC and myofibroblasts were
      Hedgehog responsive [Gli2(+)] and accumulated in parallel with fibrosis stage (P
      < 0.05). Double IHC for Ihh/CD68 showed that Ihh(+) cells were macrophages. In
      vitro studies demonstrated that SEA-stimulated macrophages to express Ihh and Shh
      mRNA (P < 0.05). Conditioned media from such macrophages induced luciferase
      production by Shh-LightII cells (P < 0.001) and Hedgehog inhibitors blocked this
      effect (P < 0.001). SEA-treated macrophages also up-regulated their own
      expression of M2 markers, and Hh pathway inhibitors abrogated this response (P <
      0.01). Inhibition of the Hedgehog pathway in LSEC blocked SEA-induced migration
      and tube formation. CONCLUSION: SEA stimulates liver macrophages to produce Hh
      ligands, which promote alternative activation of macrophages, fibrogenesis and
      vascular remodelling in schistosomiasis.

PMID- 23121642
TI  - Sex hormone binding globulin and insulin resistance.
AB  - Sex hormone binding globulin (SHBG) is a glycoprotein composed of two 373-amino
      acid subunits. The SHBG gene and a promotor region have been identified. The SHBG
      receptor has yet to be cloned but is known to act through a G-protein-linked
      second-messenger system following plasma membrane binding. The principal function
      of SHBG has traditionally been considered to be that of a transport protein for
      sex steroids, regulating circulating concentrations of free (unbound) hormones
      and their transport to target tissues. Recent research suggests that SHBG has
      functions in addition to the binding and transport of sex steroids. Observational
      studies have associated a low SHBG concentration with an increased incidence of
      type 2 diabetes mellitus (DM) independent of sex hormone levels in men and women.
      Genetic studies using Mendelian randomization analysis linking three single
      nucleotide polymorphisms of the SHBG gene to risk of developing type 2 DM suggest
      SHBG may have a role in the pathogenesis of type 2 DM. The correlation between
      SHBG and insulin resistance that is evident in a number of cross-sectional
      studies is in keeping with the suggestion that the association between SHBG and
      incidence of type 2 DM is explained by insulin resistance. Several potential
      mechanisms may account for this association, including the identification of
      dietary factors that influence SHBG gene transcription. Further research to
      characterize the SHBG-receptor and the SHBG second messenger system is required.
      An interventional study examining the effects on insulin resistance of altering
      SHBG concentrations may help in determining whether this association is causal.

PMID- 23121641
TI  - Efficacy and safety of thymoglobulin and basiliximab in kidney transplant
      patients at high risk for acute rejection and delayed graft function.
AB  - OBJECTIVES: To compare the efficacy and safety of thymoglobulin compared with
      basiliximab in patients who had kidney transplants and are at high risk for acute
      rejection and delayed graft function. MATERIALS AND METHODS: A retrospective
      review of patients who had 1 or more risk factors for acute rejection and delayed
      graft function and who were given either thymoglobulin or basiliximab for
      induction therapy. Incidences of acute rejection, antibody-treated acute
      rejection, delayed graft function, chronic rejection, cancer, infection,
      leucopenia, and thrombocytopenia were compared between thymoglobulin and
      basiliximab groups. Serum creatinine levels within 1 year and long-term graft and
      patient survival also were compared. RESULTS: A total of 327 patients were
      included. Incidences of acute rejection, antibody-treated acute rejection,
      delayed graft function, and chronic rejection were significantly lower in the
      thymoglobulin group than in the basiliximab group (P < .05). Serum creatinine
      levels were lower in the thymoglobulin group on postoperative days 7, 14, and 30
      (P < .05). There were no statistically significant differences regarding long
      term graft and patient survival, cancer, or total infection rate between the
      groups. Incidences of Cytomegalovirus infection, leucopenia, and thrombocytopenia
      were significantly higher in the thymoglobulin group (P < .05). CONCLUSIONS:
      Thymoglobulin may improve short-term outcomes, compared with basiliximab, in
      patients who had kidney transplants and are at high risk for acute rejection and
      delayed graft function. However, long-term outcomes are similar with
      thymoglobulin and basiliximab.

PMID- 23121643
TI  - Differential contributions of development and learning to infants' knowledge of
      object continuity and discontinuity.
AB  - Sixty infants divided evenly between 5 and 7 months of age were tested for their
      knowledge of object continuity versus discontinuity with a predictive tracking
      task. The stimulus event consisted of a moving ball that was briefly occluded for
      20 trials. Both age groups predictively tracked the ball when it disappeared and
      reappeared via occlusion, but not when it disappeared and reappeared via
      implosion. Infants displayed high levels of predictive tracking from the first
      trial in the occlusion condition, and showed significant improvement across
      trials in the implosion condition. These results suggest that infants possess
      embodied knowledge to support differential tracking of continuously and
      discontinuously moving objects, but this tracking can be modified by visual
      experience.

PMID- 23121644
TI  - Identification and typing of Francisella tularensis with a highly automated
      genotyping assay.
AB  - A PCR assay was developed to genotypically characterize Francisella tularensis
      and F. novicida. An integrated and partially redundant set of markers was
      selected to provide positive identification of these species, identify subspecies
      of F. tularensis and genotype 14 variable number tandem repeat (VNTR) markers.
      Assay performance was evaluated with 117 Francisella samples. Sample DNA was
      amplified, and the masses of the PCR products were determined with electrospray
      ionization/time of flight mass spectrometry (ESI-MS). The base compositions of
      the PCR amplicons were derived from these high-accuracy mass measurements and
      contrasted with databased information associated with each of the 25 assay
      markers. Species and subspecies determinations for all samples were fully
      concordant with results from established typing methods, and VNTR markers
      provided additional discrimination among samples. Sequence variants were observed
      with a number of assay markers, but these did not interfere with sample
      characterization, and served to increase the genetic diversity detected by the
      assay.

PMID- 23121645
TI  - Quartz crystal microbalance (QCM): useful for developing procedures for
      immobilization of proteins on solid surfaces.
AB  - We demonstrate the combined use of liquid and air measurements with the quartz
      crystal microbalance (QCM) for quantitative analysis of multistep reaction
      procedures leading to immobilized proteins on solid surfaces. Reactions are
      conducted on the surfaces of QCM sensor crystals and are quantified by
      measurements of resonant frequency of the crystals before and after each reaction
      step. When reactions are conducted in the flow cell of the QCM in the presence of
      solvent, measurement of resonant frequency can be made in situ (liquid
      measurement). When reactions cannot be conducted in the flow cell because of
      temperatures or solvents not tolerated by the cell, frequency can be measured
      after evaporation of solvent (air measurement). Each reaction step can be
      analyzed by either liquid or air measurement so that the whole multistep
      procedure is addressed, no matter how diverse the chemical nature of the steps.
      We conducted identical multistep procedures on two different starting surfaces,
      gold and silica, and found comparable results.

PMID- 23121647
TI  - Harms and responsibilities associated with battery-operated implants (BOI): who
      controls postmortem explantation?
AB  - The postmortem issues raised by battery-operated implants (BOI) are complex and
      issues of consent, setting (clinical vs research), and environmental risks have
      received little attention in bioethics literature. Analyzing the issues, the
      following are argued: (1) Patients receiving BOIs should sign a consent form that
      includes a requirement for postmortem explant of the device; (2) BOI consent
      forms should require the explanted devices be returned to their manufacturers for
      Returned Product Analysis; (3) Failure to explant and analyze devices from the
      research setting fails the research goal of generation of knowledge for the
      benefit of future patients; (4) Failure to explant and analyze devices from the
      clinical setting allows product defects to be potentially hidden from patients,
      families, clinicians, manufacturers, and regulatory agencies; (5) Bodies buried
      with BOIs potentially harm the environment; (6) Religious or philosophical
      objections to autopsy should not supersede the duty to explant and analyze BOIs;
      (7) The concepts herein for BOIs could potentially extend to non-BOI if the
      device has failure modes that can lead to a potentially life-threatening event or
      can cause permanent debilitating health issues, and the burial or cremation of
      the device poses environmental harm. In these situations, neither the patient
      (premortem) nor family (postmortem) should have the right to refuse explant.

PMID- 23121646
TI  - Trends in chronic myeloid leukemia incidence and survival in the United States
      from 1975 to 2009.
AB  - The use of interferon-alpha and allogeneic stem cell transplant and more recently
      of tyrosine kinase inhibitors (TKIs) have improved the outcome of patients with
      chronic myeloid leukemia (CML). We performed a population-based study of CML to
      evaluate relative survival (RS) trend by treatment eras. All instances of CML
      diagnosed between 1975 and 2009 reported in the Surveillance, Epidemiology and
      End Results databases were reviewed. The incidence of CML was 1.75/100 000
      persons per year and increased with age. The incidence was highest in Detroit and
      lowest among Asians. The 5-year RS ratios increased from 0.26 in patients
      diagnosed in 1975-1989 to 0.36 in 1990-2000 and 0.56 in 2001-2009. There was a
      significant improvement in 5-year RS ratios in the 2005-2009 calendar period
      compared to the 2001-2004 period (p < 0.05), corresponding to the introduction of
      second-generation TKIs. Age was the most important prognostic factor for RS, but
      the improvement in 5-year RS ratios was observed in all age groups except the
      group aged < 15 years (p > 0.05), including adolescents and young adults and
      elderly patient groups. There are ethnic and geographic variations in the
      incidence of CML. The RS improved with each treatment era, with the greatest
      improvement in all age groups occurring during the TKI era.

PMID- 23121648
TI  - Rational design of selective organoruthenium inhibitors of protein tyrosine
      phosphatase 1B.
AB  - Protein tyrosine phosphatases (PTPs) belong to a large family of important
      regulatory enzymes involved in vital mammalian signaling pathways. Selective
      inhibitors of PTPs are highly valuable from a therapeutic standpoint given their
      association with various pathological conditions. One such target is PTP-1B which
      has previously been linked to diabetes and cancer. However, developing a
      selective inhibitor against PTP-1B has proven to be daunting because the enzyme
      shares a high degree of structural homology with TC-PTP, an essential PTP
      involved in modulating immune functions. To address this challenge, a series of
      organoruthenium complexes was developed to bind at the PTP substrate-binding site
      while simultaneously target the peripheral structural space. By capitalizing on
      the potential difference in the structural environment proximal to the active
      site between different PTPs, selectivity toward PTP-1B over TC-PTP was improved,
      paving the way for organoruthenium complexes as selective PTP-1B
      metalloinhibitors. 

PMID- 23121649
TI  - Chemoselective cross-coupling reactions with differentiation between two
      nucleophilic sites on a single aromatic substrate.
AB  - A new thiophene building block, containing both a stannyl group and a boronic
      ester, was prepared. From this starting material, a general, nucleophile
      selective one-pot reaction was developed, exploiting the different reactivities
      of the Stille and Suzuki-Miyaura cross-coupling reactions. A series of aromatic
      electrophiles were used to demonstrate the high functional group tolerance.

PMID- 23121650
TI  - Reversible switching of the interparticle distance in DNA-templated gold
      nanoparticle dimers.
AB  - We produce gold nanoparticle dimers with a surface-to-surface distance that
      varies reversibly by a factor of 3 when hybridizing or removing a single target
      DNA strand. The dimers are built on one DNA template that features a stem-loop
      enabling the interparticle distance change. Using electrophoresis, we reach 90%
      sample purities and demonstrate that this chemical process is reversible in
      solution at room temperature for a low molar excess of the target DNA strand. The
      kinetics of the reaction is asymmetric due to steric hindrance in the stem-loop
      opening process. Furthermore, a statistical analysis of cryo-electron microscopy
      measurements allows us to provide the first quantitative analysis of distance
      changes in chemically switchable nanoparticle assemblies.

PMID- 23121651
TI  - Spinal manifestations of spontaneous intracranial hypotension.
AB  - OBJECT: The goal of the study was to elucidate the spinal manifestations of
      spontaneous intracranial hypotension. METHODS: The authors reviewed the medical
      records and imaging studies of 338 consecutive patients with spontaneous
      intracranial hypotension who were evaluated at their institution between 2001 and
      2010. RESULTS: Twenty patients (6%; mean age 35.8 [range 16 to 60 years]; 5 males
      and 15 females) had convincing signs or symptoms referable to the spinal cord or
      spinal nerve roots. The spinal manifestations consisted of radiculopathy in 11
      patients (unilateral in 8 and bilateral in 3), myelopathy in 8 patients, and
      bibrachial amyotrophy in 1 patient. The cervical spine was involved in 12
      patients, the thoracic spine in 5, and the lumbosacral spine in 3. The spinal
      symptoms were positional in only 3 patients. The spinal manifestations occurred
      around the time of the headache onset in 16 patients, and months to years after
      the positional headache had resolved in 4 patients. A large extrathecal CSF
      collection causing compression of the spinal cord or nerve root was responsible
      for the spinal manifestations in the majority of patients. Treatment of the
      spinal CSF leak resulted in resolution of the spinal manifestations along with
      the headache, except for those in the patient with bibrachial amyotrophy.
      CONCLUSIONS: Spinal manifestations are uncommon in cases of spontaneous
      intracranial hypotension, occurring in about 6% of patients, but myelopathy and
      radiculopathy involving all spinal segments do occur. Unlike the headache, the
      spinal manifestations usually are not positional and are caused by mass effect
      from an extradural CSF collection.

PMID- 23121652
TI  - Urological injury as a complication of the transpsoas approach for discectomy and
      interbody fusion.
AB  - Transpsoas discectomy and interbody fusion has become an increasingly popular
      method of achieving lumbar interbody fusion, but reports of neurological,
      vascular, and gastrointestinal complications associated with this procedure have
      been described in the literature. To date, however, ureteral complications have
      not been reported with this procedure. The authors report 2 cases of ureteral
      injury and 1 case of renal injury following this procedure. A low index of
      suspicion is warranted to work up any patient having flank or abdominal symptoms
      after undergoing transpsoas discectomy and interbody fusion.

PMID- 23121653
TI  - The seasonality of postoperative infection in spine surgery.
AB  - OBJECT: Studies from many disciplines have found an association with the summer
      months, elevated temperature, humidity, and an increased rate of infection. The
      "July effect," a hypothesis that the inexperience of new house staff at the
      beginning of an academic year leads to an increase in wound complications, has
      also been considered. Finally, an increase in trauma-related admissions in the
      summer months is likely to result in an increased incidence of postoperative
      infections. Two previous studies revealed mixed results concerning perioperative
      spinal wound infections in the summer months. The purpose of this study was to
      determine the months and/or seasons of the year that display significant
      fluctuation of postoperative infection rate in spine surgery. Based on the idea
      that infection rates are susceptible to seasonal factors, the authors
      hypothesized that spinal infections would increase during the summer months.
      METHODS: Inclusion criteria were all spine surgery cases at a single tertiary
      referral institution between January 2005 and December 2009; 8122 cases were
      included. Patients presenting with a contaminated wound or active infection were
      excluded. Infection rates were calculated on a monthly and seasonal basis and
      compared. RESULTS: A statistically significant increase in the infection rate was
      present on both a seasonal and monthly basis (p = 0.03 and p = 0.024) when
      looking at the seasonal change from spring to summer. A significant decrease in
      the infection rate was seen on a seasonal basis during the change from fall to
      winter (p = 0.04). The seasonal rate of infection was highest in the summer
      (4.1%) and decreased to the lowest point in the spring (2.8%) (p = 0.03).
      CONCLUSIONS: At the authors' institution, spine surgeries performed during the
      summer and fall months were associated with a significantly higher incidence of
      wound infection compared with the winter and spring. These data support the
      existence of a seasonal effect on perioperative spinal infection rates, which may
      be explained by seasonal variation in weather patterns and house staff
      experience, among other factors.

PMID- 23121654
TI  - Phaeohyphomycosis caused by Pyrenochaeta romeroi mimicking a plantar wart in a
      kidney transplant recipient.

PMID- 23121655
TI  - Interior engineering of a viral nanoparticle and its tumor homing properties.
AB  - The development of multifunctional nanoparticles for medical applications is of
      growing technological interest. A single formulation containing imaging and/or
      drug moieties that is also capable of preferential uptake in specific cells would
      greatly enhance diagnostics and treatments. There is growing interest in plant
      derived viral nanoparticles (VNPs) and establishing new platform technologies
      based on these nanoparticles inspired by nature. Cowpea mosaic virus (CPMV)
      serves as the standard model for VNPs. Although exterior surface modification is
      well-known and has been comprehensively studied, little is known of interior
      modification. Additional functionality conferred by the capability for interior
      engineering would be of great benefit toward the ultimate goal of targeted drug
      delivery. Here, we examined the capacity of empty CPMV (eCPMV) particles devoid
      of RNA to encapsulate a wide variety of molecules. We systematically investigated
      the conjugation of fluorophores, biotin affinity tags, large molecular weight
      polymers such as poly(ethylene glycol) (PEG), and various peptides through
      targeting reactive cysteines displayed selectively on the interior surface.
      Several methods are described that mutually confirm specific functionalization of
      the interior. Finally, CPMV and eCPMV were labeled with near-infrared
      fluorophores and studied side-by-side in vitro and in vivo. Passive tumor
      targeting via the enhanced permeability and retention effect and optical imaging
      were confirmed using a preclinical mouse model of colon cancer. The results of
      our studies lay the foundation for the development of the eCPMV platform in a
      range of biomedical applications.

PMID- 23121656
TI  - Pathological bacterial translocation in cirrhosis: pathophysiology, diagnosis and
      clinical implications.
AB  - Bacterial translocation (BT) is defined by the passage of viable indigenous
      bacteria from the intestinal lumen to mesenteric lymph nodes (MLNs) and other
      territories, and its diagnostic criteria rely on the isolation of viable bacteria
      in MLNs. Small intestinal overgrowth, increased intestinal permeability and
      immunological alterations are the main factors involved in its pathogenesis. BT
      is obviously difficult to identify in patients with cirrhosis, and alternative
      methods have been proposed instead. Bacterial DNA detection and species
      identification in serum or ascitic fluid has been proposed as a reliable marker
      of BT. Bacterial products, such as endotoxin, or bacterial DNA can translocate to
      extra-intestinal sites and promote an immunological response similar to that
      produced by viable bacteria. Therefore, pathological BT plays an important role
      in the pathogenesis of the complications of cirrhosis, not only in infections,
      but by exerting a profound inflammatory state and exacerbating the haemodynamic
      derangement. This may promote in turn the development of hepatorenal syndrome,
      hepatic encephalopathy and other portal hypertension-related complications.
      Therapeutic approaches for the prevention of BT in experimental and human
      cirrhosis are summarized. Finally, new investigations are needed to better
      understand the pathogenesis and consequences of translocation by viable bacteria
      (able to grow in culture), or non-viable BT (detection of bacterial fragments
      with negative culture) and open new therapeutic avenues in patients with
      cirrhosis.

PMID- 23121657
TI  - Self-reported and actual hepatitis C virus infection status.

PMID- 23121658
TI  - Current pharmacological treatments for tinnitus.
AB  - INTRODUCTION: Tinnitus, the phantom perception of sound, is a highly prevalent
      disorder and treatment is elusive. AREAS COVERED: This review focuses on clinical
      research regarding pharmacological treatments for tinnitus. The authors searched
      PubMed databases for English language articles related to pharmacological
      treatment of tinnitus, published through August 2012. The keywords "tinnitus AND
      pharmacological treatment" and "tinnitus AND drugs" were used. The search focused
      on clinical trials, but was complemented by other articles and information from
      clinical trial registries. EXPERT OPINION: Despite the significant unmet clinical
      need for a safe and effective drug for tinnitus relief, there is currently no EMA
      or FDA-approved drug on the market. Even a drug that produces a small but
      significant effect would have a huge therapeutic impact. At present, evidence
      based pharmacological approaches are limited to the treatment of comorbidities
      such as depression, anxiety, or insomnia. In the last few years there have been
      significant advances in the understanding of the pathophysiology of the different
      forms of tinnitus, the establishment of valid animal models, and the development
      of clinical trial methodology. A glimpse of hope is appearing in the horizon as
      an increasing number of pharmaceutical industries now have compounds targeting
      tinnitus in their pipeline.

PMID- 23121659
TI  - The RNA-binding protein MARTA2 regulates dendritic targeting of MAP2 mRNAs in rat
      neurons.
AB  - Dendritic targeting of mRNAs encoding the microtubule-associated protein 2 (MAP2)
      in neurons involves a cis-acting dendritic targeting element. Two rat brain
      proteins, MAP2-RNA trans-acting protein (MARTA)1 and MARTA2, bind to the cis
      element with both high affinity and specificity. In this study, affinity-purified
      MARTA2 was identified as orthologue of human far-upstream element binding protein
      3. In neurons, it resides in somatodendritic granules and dendritic spines and
      associates with MAP2 mRNAs. Expression of a dominant-negative variant of MARTA2
      disrupts dendritic targeting of endogenous MAP2 mRNAs, while not noticeably
      altering the level and subcellular distribution of polyadenylated mRNAs as a
      whole. Finally, MAP2 transcripts associate with the microtubule-based motor KIF5
      and inhibition of KIF5, but not cytoplasmic dynein function disrupts extrasomatic
      trafficking of MAP2 mRNA granules. Thus, in neurons MARTA2 appears to represent a
      key trans-acting factor involved in KIF5-mediated dendritic targeting of MAP2
      mRNAs.

PMID- 23121660
TI  - Multiple catalytic activities of Escherichia coli lysyl-tRNA synthetase (LysU)
      are dissected by site-directed mutagenesis.
AB  - The heat-inducible lysyl-tRNA synthetase from Escherichia coli (LysU;
      EC6/1/1/6.html) converts ATP to diadenosine tri- and tetraphosphates
      (Ap(3)A/Ap(4)A) in the presence of L-lysine/Mg(2+)/Zn(2+). To understand LysU in
      more detail, 26 mutants were prepared: six of E264, four of R269 and sixteen
      mutants by alanine-scanning of the inner shell/motif 2 loop. In the presence of
      glycerol and absence of exogenously added Zn(2+)/L-lysine, we unexpectedly found
      that E264K catalysed the production of glycerol-3-phosphate, powered by ATP
      turnover to ADP. E264Q and E264N are also capable of this activity, but all three
      show little formation of Ap(4)A/Ap(3)A under normal conditions (additional
      Zn(2+)/L-lysine/Mg(2+)). By contrast, wild-type LysU has a weaker glycerol kinase
      like capability in the absence of Zn(2+) and is dominated by Ap(4)A/Ap(3)A
      synthesis in its presence. Kinetic and isothermal titration calorimetry results
      suggest that E264 is a crucial residue for Zn(2+) promotion of Ap(4)A/Ap(3)A
      synthesis. This is consistent with the hypothesis that E264 provides an anchor
      point for a Zn(2+) ion complexed to the active site, with simultaneous
      coordination to the enzyme bound lysyl-adenylate intermediate and secondary
      substrate ATP/ADP. The glycerol kinase-like activity is uncovered on disruption
      of this specific coordination.

PMID- 23121661
TI  - SATB1 expression and its association with tumour prognosis in systemic
      malignancies: an evolving concept in oncology.

PMID- 23121662
TI  - Non-human immunodeficiency virus Pneumocystis jiroveci pneumonia.

PMID- 23121663
TI  - Cyclosporin A therapy on idiopathic thrombotic thrombocytopenic purpura in the
      relapse setting: two case reports and a review of the literature.
AB  - BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening
      disease, characterized by microangiopathic hemolytic anemia, thrombocytopenia,
      fever, neurologic disturbances, and renal failure. Plasma therapy has
      dramatically improved prognosis of TTP, whereas recurrent acute episodes still
      occur in approximately 40% of patients. Moreover, patients with acquired ADAMTS13
      deficiency, which is a significant factor for relapse, may require additional
      immunosuppressive treatment to get a durable remission. STUDY DESIGN AND METHODS:
      We hereby report two patients with a history of relapsed idiopathic TTP, who both
      received cyclosporin A (CSA) as a prophylactic manner after the remission was
      achieved. We also discuss the efficacy of CSA in patients with relapsed
      idiopathic TTP with a review of the published literature. RESULTS: Under CSA
      therapy, both patients maintained their clinical remission state, and the
      ADAMTS13 levels were normalized. CONCLUSION: To conclude, CSA therapy may be
      useful for the prevention of relapsed idiopathic TTP in patients with a history
      of frequent relapses.

PMID- 23121664
TI  - No decision about me without me: concordance operationalised.
AB  - AIMS AND OBJECTIVES: To demonstrate that concordance can be operationalised to
      the benefit of patients. Concordance can be understood as a composite of
      knowledge, health beliefs and collaboration. BACKGROUND: In discussing any
      clinical decision, it would be ideal if different views could be incorporated to
      reach the most coherent decision. This is a definition of concordance, a widely
      agreed ideal in nursing. There are limits, however, that make the practice of
      concordance problematic. Sometimes there is little time or willingness to discuss
      issues in depth. Some views of the world are considered more worthy than others.
      As a consequence, clinical guidelines currently prioritise easier to measure
      outcomes of negotiation, such as adherence. DESIGN: This discursive article
      argues that prioritising adherence is a fundamental error, incoherent with
      current strategic rhetoric such as the Department of Health's 'no decision about
      me without me'. METHODS: The impact of prioritising concordance is contrasted
      with adherence-based interventions. RESULTS: Where adherence is a goal of
      treatment, non-adherence is considered problematic. This value judgment is not
      useful and does not occur in a consultation that prioritises concordance.
      However, concordance is difficult to translate into clinical practice. This
      article shows that concordance can be operationalised by considering it a
      composite of health beliefs, knowledge and collaboration. CONCLUSION: The main
      thesis is that different behaviours can always be incorporated into a concordance
      framework. This negates the necessity for adherence as an endpoint in itself.
      RELEVANCE TO CLINICAL PRACTICE: Fifty per cent of people do not take medicines as
      prescribed. Interventions focused towards improving adherence are only ever
      partially successful. This is because it presupposes the clinician is right.
      Concordance by contrast is more coherent with person centred care and thus more
      likely to generate clinically meaningful outcomes for patients.

PMID- 23121665
TI  - Broadening the translational immunology landscape.
AB  - It is just over 5 years since Clinical and Experimental Immunology came under the
      direction of a new team of Editors and made a concerted effort to refresh its
      approach to promoting clinical and applied immunology through its pages. There
      were two major objectives: to foster papers in a field which, at the time, we
      loosely termed 'translational immunology'; and to create a forum for the
      presentation and discussion of immunology that is relevant to clinicians
      operating in this space. So, how are we doing with these endeavours? This brief
      paper aims to summarize some of the key learning points and successes and
      highlight areas in which translational gaps remain.

PMID- 23121666
TI  - Characterization of the interaction between astrocytes and encephalitogenic
      lymphocytes during the development of experimental autoimmune encephalitomyelitis
      (EAE) in mice.
AB  - The nature of pathogenic mechanisms associated with the development of multiple
      sclerosis (MS) have long been debated. However, limited research was conducted to
      define the interplay between infiltrating lymphocytes and resident cells of the
      central nervous system (CNS). Data presented in this report describe a novel role
      for astrocyte-mediated alterations to myelin oligodendrocyte glycoprotein
      (MOG)(35-55) -specific lymphocyte responses, elicited during the development of
      experimental autoimmune encephalitomyelitis (EAE). In-vitro studies demonstrated
      that astrocytes inhibited the proliferation and interferon (IFN)-gamma,
      interleukin (IL)-4, IL-17 and transforming growth factor (TGF)-beta secretion
      levels of MOG(35-55) -specific lymphocytes, an effect that could be ameliorated
      by astrocyte IL-27 neutralization. However, when astrocytes were pretreated with
      IFN-gamma, they could promote the proliferation and secretion levels of MOG(35
      55) -specific lymphocytes, coinciding with apparent expression of major
      histocompatibility complex (MHC)-II on astrocytes themselves. Quantitative
      polymerase chain reaction (qPCR) demonstrated that production of IL-27 in the
      spinal cord was at its highest during the initial phases. Conversely, production
      of IFN-gamma in the spinal cord was highest during the peak phase. Quantitative
      analysis of MHC-II expression in the spinal cord showed that there was a positive
      correlation between MHC-II expression and IFN-gamma production. In addition,
      astrocyte MHC-II expression levels correlated positively with IFN-gamma
      production in the spinal cord. These findings suggested that astrocytes might
      function as both inhibitors and promoters of EAE. Astrocytes prevented MOG(35-55)
      -specific lymphocyte function by secreting IL-27 during the initial phases of
      EAE. Then, in the presence of higher IFN-gamma levels in the spinal cord,
      astrocytes were converted into antigen-presenting cells. This conversion might
      promote the progression of pathological damage and result in a peak of EAE
      severity.

PMID- 23121667
TI  - Altered expression of intestinal human leucocyte antigen D-related and immune
      signalling molecules in juvenile idiopathic arthritis.
AB  - We aimed to study intestinal immune activation status in juvenile idiopathic
      arthritis (JIA) by assessing intestinal human leucocyte antigen (HLA) class II
      expression and the mRNA expression levels of the pro- and anti-inflammatory
      mediators and pattern recognition receptors. HLA-D-related (HLA-DR) expression
      was assessed using immunohistochemical staining of frozen sections in 11 children
      with JIA and 17 controls. The gene expression levels of the anti- and
      proinflammatory cytokines, lymphocyte recognition receptors and pattern
      recognition receptors were studied with reverse transcription-polymerase chain
      reaction (RT-PCR) in 14 children with JIA and 12 controls. All subjects had
      various gastrointestinal (GI) symptoms indicating endoscopic examinations, but
      eventually were not diagnosed with GI disease. In JIA patients, the expression of
      HLA-DR was increased in the crypt epithelial cells and in the epithelial basement
      membrane of the ileum when compared with the controls. Positive HLA-DR staining
      in the ileal mucosa was associated with the presence of high clinical disease
      activity of JIA and low mRNA expression of anti-inflammatory mediators, such as
      forkhead box protein P3 (FoxP3), glucocorticoid-induced tumour necrosis factor
      receptor-related protein (GITR) and transforming growth factor (TGF)-beta. Low
      ileal expression of interleukin (IL)-10, TGF-beta, FoxP3, Toll-like receptor 2
      (TLR-2) and TLR-4 transcripts correlated significantly with a high clinical
      disease activity in the JIA patients. The increased HLA-DR expression suggests
      enhanced intestinal antigen presentation in JIA. A correlation between clinical
      disease activity and low gene expression of tolerogenic mediators in the ileum
      supports the hypothesis that a link exists between the gut immune system and JIA.

PMID- 23121668
TI  - Activated natural killer T cells producing interferon-gamma elicit promoting
      activity to murine dendritic cell-based autoimmune hepatic inflammation.
AB  - As natural killer (NK) T cells play an important role in the development of
      autoimmune diseases, they should have significant roles for the pathogenesis of
      autoimmune liver disease. Implication of the NK T cells in the generation of
      autoimmune-related hepatic inflammation was investigated using a novel mouse
      model. Immunization of mice with dendritic cells (DCs) loaded with hepatocyte
      mimicking hepatocellular carcinoma cells (DC/Hepa1-6) induces cytotoxic T
      lymphocytes (CTL) capable of killing hepatocytes. Subsequent administration of
      interleukin (IL)-12, a potent interferon-gamma (IFN-gamma) inducer, to the
      immunized mice generates autoimmune hepatic inflammation (AHI), as reported
      previously. Upon onset of the AHI response, the number of intrahepatic CD3(+) NK1
      . 1(+) NK T cells increased markedly, along with a decrease in the number of
      splenic NK T cells, augmented expression of CXCR6 on intrahepatic NK T cells and
      CXCL16 in hepatic tissue, suggesting that NK T cells were recruited into the
      inflamed liver. The NK T cells were strongly positive for CD69 and produced IFN
      gamma, but not IL-4. AHI activity was attenuated markedly in CD1d(-/-) NK T cell
      deficient mice, indicating that NK T cells play a pivotal role in the development
      of AHI. Mice treated with DC/Hepa1-6 and alpha-galactosylceramide, a potent NK T
      cell activator, also exhibited similar hepatic inflammation, in which activated
      NK T cells producing IFN-gamma and CD8(+) T cells cytotoxic to hepatocytes were
      induced in liver-infiltrating mononuclear cells. Activated NK T cells producing
      IFN-gamma potentiate DC-based AHI in the mouse model.

PMID- 23121669
TI  - Epitope recognition patterns of thyroglobulin antibody in sera from patients with
      Hashimoto's thyroiditis on different thyroid functional status.
AB  - Thyroglobulin antibody (TgAb) is a diagnostic serological marker of Hashimoto's
      thyroiditis (HT). The pathogenesis of HT progression from euthyroidism to
      hypothyroidism is still not clear. Epitope recognition patterns of TgAb have been
      shown to be different in individuals who are euthyroid or who have clinical
      disease. The aim of our study was to investigate the role of thyroglobulin (Tg)
      epitope specificities in HT progression. Sera from 107 patients with newly
      diagnosed HT were collected and divided into three groups: patients with
      hypothyroidism (H, n = 39), subclinical hypothyroidism (sH, n = 31) and
      euthyroidism (Eu, n = 37). A panel of Tg murine monoclonal antibodies (mAb: PB2,
      5E6, 1D4, 5F9, Tg6) and a hircine pAb (N15) were employed as the probe antibodies
      to define the antigenic determinants recognized by HT sera on competitive enzyme
      linked immunosorbent assays (ELISAs). Eight of 39 sera samples in H and seven of
      31 in sH inhibited PB2 binding, respectively, whereas none did in Eu. The ratio
      of sera samples, inhibiting PB2 binding in Eu, was significantly lower than that
      in H (P = 0.011) and in sH (P = 0.008). For N15, five of 39 sera samples in H,
      six of 31 in sH and 15 of 37 in Eu inhibited its binding, respectively. The ratio
      of sera samples, inhibiting N15 binding in Eu, was significantly higher than that
      in H (P = 0.013). Our study demonstrated that HT patients in different thyroid
      functional status exhibited different Tg epitope recognition patterns. Epitope
      patterns of TgAb might be used as a prediction marker of HT progression.

PMID- 23121670
TI  - Enhanced therapeutic effect of B cell-depleting anti-CD20 antibodies upon
      combination with in-situ dendritic cell vaccination in advanced lymphoma.
AB  - The present standard of care for B cell non-Hodgkin's lymphoma includes the anti
      CD20 monoclonal antibody rituximab. Although combination treatments with
      chemotherapy and rituximab improved the duration of remissions and overall
      survival in indolent B cell lymphoma, the disease is essentially incurable. Thus,
      new therapeutic approaches are needed. One such approach is active immunization.
      Given that rituximab depletes both malignant and normal B cells, it is expected
      to impair humoral immune responses in vaccinated patients. Hence, optimal
      vaccination strategies for rituximab-treated patients require induction of
      effector T cells, which can be achieved by dendritic cell (DC) vaccines. We have
      demonstrated in a mouse model that chemotherapy combined with DC vaccines was
      therapeutically effective. However, efficacy was related to tumour size at the
      onset of treatment, decreasing in correlation with increasing tumour burdens. We
      therefore examined whether, in spite of its low efficacy in advanced disease, DC
      vaccination may synergize with anti-CD20 antibodies to enhance therapy. Lymphoma
      bearing mice were treated with cyclophosphamide, anti-CD20 antibodies and an
      intratumoral DC vaccine. Results clearly demonstrated the enhanced therapeutic
      effect of this combination treatment. Thus, under conditions of disseminated
      disease, when either anti-CD20 antibody treatment or vaccination showed
      insufficient efficacy, their combination resulted in synergism that mediated long
      term survival. We demonstrated further that the combination of antibody and
      vaccine induced T cell-mediated anti-tumour immune responses with long-term
      memory. Combination treatments including tumour cell-loaded DC vaccines may
      therefore provide a strategy for enhancing therapy in rituximab-treated patients.

PMID- 23121671
TI  - Helicobacter pylori induces in-vivo expansion of human regulatory T cells through
      stimulating interleukin-1beta production by dendritic cells.
AB  - Helicobacter pylori is one of the most common infections in the world. Despite
      inciting inflammation, immunological clearance of the pathogen is often
      incomplete. CD4(+) CD25(hi) forkhead box protein 3 (FoxP3(+)) regulatory T cells
      (T(regs)) are potent suppressors of different types of immune responses and have
      been implicated in limiting inflammatory responses to H. pylori. Investigating
      the influence of H. pylori on T(reg) function and proliferation, we found that H.
      pylori-stimulated dendritic cells (DCs) induced proliferation in T(regs) and
      impaired their suppressive capability. This effect was mediated by interleukin
      (IL)-1beta produced by H. pylori-stimulated DCs. These data correlated with in
      vivo observations in which H. pylori(+) gastric mucosa contained more T(regs) in
      active cell division than uninfected stomachs. Inciting local proliferation of
      T(regs) and inhibiting their suppressive function may represent a mechanism for
      the chronic gastritis and carcinogenesis attributable to H. pylori.

PMID- 23121672
TI  - Defects in the vasoactive intestinal peptide (VIP)/VPAC system during early
      stages of the placental-maternal leucocyte interaction impair the maternal
      tolerogenic response.
AB  - Successful embryo implantation occurs followed by a local inflammatory/T helper
      type 1 (Th1) response, subsequently redirected towards a tolerogenic predominant
      profile. The lack of control of this initial local inflammatory response may be
      an underlying cause of early pregnancy complications as recurrent spontaneous
      abortions (RSA). Considering that vasoactive intestinal peptide (VIP) mediates
      anti-inflammatory and tolerogenic effects in several conditions we hypothesized
      that VIP might contribute to tolerance towards trophoblast antigens during the
      early interaction of maternal leucocytes and trophoblast cells. In this study we
      investigated VIP/VPAC system activity and expression on maternal peripheral blood
      mononuclear cells (PBMCs) after interaction with immortalized trophoblast cells
      (Swan-71 cell line) as an in-vitro model of feto-maternal interaction, and we
      analysed whether it modulates maternal regulatory T cell (T(reg))/Th1 responses.
      We also investigated the contribution of the endogenous VIP/VPAC system to RSA
      pathogenesis. VIP decreased T-bet expression significantly, reduced monocyte
      chemotactic protein-1 (MCP-1) and nitrite production in co-cultures of PBMCs from
      fertile women with trophoblast cells; while it increased the frequency of CD4(+)
      CD25(+) forkhead box protein 3 (Foxp3)(+) cells, transforming growth factor (TGF)
      beta expression and interleukin (IL)-10 secretion. These effects were prevented
      by VIP-specific antagonist. Interestingly, PBMCs from RSA patients displayed
      significantly higher T-bet expression, lower T(reg) frequency and lower frequency
      of VIP-producer CD4 lymphocytes after the interaction with trophoblast cells.
      Moreover, the patients displayed a significantly lower frequency of endometrial
      CD4(+) VIP(+) cells in comparison with fertile women. VIP showed a Th1-limiting
      and T(reg) -promoting response in vitro that would favour early pregnancy
      outcome. Because RSA patients displayed defects in the VIP/VPAC system, this
      neuropeptide could be a promising candidate for diagnostic biomarker or surrogate
      biomarker for recurrent spontaneous abortions.

PMID- 23121673
TI  - Chronic immune activation in common variable immunodeficiency (CVID) is
      associated with elevated serum levels of soluble CD14 and CD25 but not
      endotoxaemia.
AB  - Common variable immunodeficiency (CVID), the most frequent symptomatic
      immunoglobulin primary immunodeficiency, is associated with chronic T cell
      activation and reduced frequency of CD4(+)  T cells. The underlying cause of
      immune activation in CVID is unknown. Microbial translocation indicated by
      elevated serum levels of lipopolysaccharide and soluble CD14 (sCD14) has been
      linked previously to systemic immune activation in human immunodeficiency
      virus/acquired immune deficiency syndrome (HIV-1/AIDS), alcoholic cirrhosis and
      other conditions. To address the mechanisms of chronic immune activation in CVID,
      we performed a detailed analysis of immune cell populations and serum levels of
      sCD14, soluble CD25 (sCD25), lipopolysaccharide and markers of liver function in
      35 patients with CVID, 53 patients with selective immunoglobulin (Ig)A deficiency
      (IgAD) and 63 control healthy subjects. In CVID subjects, the concentration of
      serum sCD14 was increased significantly and correlated with the level of sCD25, C
      reactive protein and the extent of T cell activation. Importantly, no increase in
      serum lipopolysaccharide concentration was observed in patients with CVID or
      IgAD. Collectively, the data presented suggest that chronic T cell activation in
      CVID is associated with elevated levels of sCD14 and sCD25, but not with systemic
      endotoxaemia, and suggest involvement of lipopolysaccharide-independent
      mechanisms of induction of sCD14 production.

PMID- 23121674
TI  - Immunophenotyping of putative human B1 B cells in healthy controls and common
      variable immunodeficiency (CVID) patients.
AB  - B1 B cells represent a unique subset of B lymphocytes distinct from conventional
      B2 B cells, and are important in the production of natural antibodies. A
      potential human homologue of murine B1 cells was defined recently as a CD20(+)
      CD27(+) CD43(+) cell. Common variable immunodeficiency (CVID) is a group of
      heterogeneous conditions linked by symptomatic primary antibody failure. In this
      preliminary report, we examined the potential clinical utility of introducing
      CD20(+) CD27(+) CD43(+) B1 cell immunophenotyping as a routine assay in a
      diagnostic clinical laboratory. Using a whole blood assay, putative B1 B cells in
      healthy controls and in CVID patients were measured. Peripheral blood from 33
      healthy donors and 16 CVID patients were stained with relevant monoclonal
      antibodies and underwent flow cytometric evaluation. We established a rapid,
      whole blood flow cytometric assay to investigate putative human B1 B cells.
      Examination of CD20(+) CD27(+) CD43(+) cells is complicated by CD3(+) CD27(+)
      CD43(hi) T cell contamination, even when using stringent CD20 gating. These can
      be excluded by gating on CD27(+) CD43(lo-int) B cells. Although proportions of
      CD20(+)CD27(+)CD43(lo-int) cells within B cells in CVID patients were decreased
      by 50% compared to controls (P < 0.01), this was not significant when measured as
      a percentage of all CD27(+) B cells (P = 0.78) [corrected]. Immunophenotypic
      overlap of this subset with other innate-like B cells described recently in
      humans is limited. We have shown that putative B1 B cell immunophenotyping can be
      performed rapidly and reliably using whole blood. CD20(+) CD27(+) CD43(lo-int)
      cells may represent a distinct B1 cell subset within CD27(+) B cells. CVID
      patients were not significantly different from healthy controls when existing
      CD27(+) B cell deficiencies were taken into account.

PMID- 23121675
TI  - Schistosoma mansoni tetraspanning orphan receptor (SmTOR): a new vaccine
      candidate against schistosomiasis.
AB  - One approach to fight against schistosomiasis is to develop an efficient vaccine.
      Schistosoma mansoni tetraspanning orphan receptor (SmTOR) might be a vaccine
      candidate, as it is a tegument membrane protein expressed most highly in
      cercariae. In this study we characterized the recombinant first extracellular
      domain of SmTOR (rSmTORed1) as having the expected property to bind C2 of
      complement similarly to a smaller peptide of the same domain, and to produce
      specific and high-titre antibodies in BALB/c mice immunized using complete
      Freund's adjuvant/incomplete Freund's adjuvant (CFA/IFA). Immunization was
      protective against parasite infection, as demonstrated by a significant decrease
      in worm burden in immunized BALB/c mice versus the control groups over two
      independent trials [64 and 45% reduction for mean adult worm burden in immunized
      versus phosphate-bufferd saline (PBS) injected mice]. Interestingly, infection by
      itself did not lead to the generation of anti-rSmTORed1 antibodies, corresponding
      to the low frequency of specific anti-rSmTORed1 antibodies detected in the sera
      of patients infected with S. mansoni (2/20; 10%). These data suggest that, as
      opposed to the natural infection during which SmTOR induces antibodies only
      rarely, immunization with its smaller first extracellular domain might be more
      efficient.

PMID- 23121678
TI  - Synthesis and chiroptical properties of arylimines of cholest-4-ene-3,6-dione.
AB  - In the hope of generating a new class of materials with large optical rotations,
      various arylamines were condensed with cholest-4-ene-3,6-dione (2) to give 3
      arylimino steroids. These compounds possess moderately high specific rotations
      ([alpha](D) ~300-800) and strong circular dichroism. One such derivative, 3-(4
      methoxyphenylimino)cholest-4-en-6-one (3), crystallizes as the (E)-imine and upon
      dissolution undergoes mutarotation to an equilibrium mixture of (E)- and (Z)
      isomers with a half-life of approximately 1 h at room temperature, as judged by
      both NMR spectroscopy and polarimetry.

PMID- 23121676
TI  - Serum levels and mesenteric fat tissue expression of adiponectin and leptin in
      patients with Crohn's disease.
AB  - Crohn's disease (CD) is characterized by inflammation and an aetiology that is
      still unknown. Hypertrophy of mesenteric fat is a reflection of disease activity,
      as this fat covers the entire length of the affected area. Adipocytes synthesize
      leptin and adiponectin, adipocytokines responsible for pro- and anti-inflammatory
      effects. Therefore, we evaluated serum levels of adiponectin and leptin, as well
      as mesenteral expression of adiponectin in active CD and those in remission.
      Sixteen patients with ileocaecal CD followed at the Outpatient Clinic,
      Coloproctology Unit of University of Campinas Clinical Hospital, participated in
      the study. Analysis of serum adiponectin and leptin by enzyme-linked
      immunosorbent assay was performed in patients with active CD (ACD group),
      remission CD (RCD group) and in six healthy controls. Ten patients with active
      ileocaecal CD (FCD group) and eight patients with non-inflammatory disease
      selected for surgery were also studied. The specimens were snap-frozen and the
      expression of adiponectin was determined by immunoblot of protein extracts. Serum
      C-reactive protein levels were higher in the ACD group when compared to the
      others and no difference of body mass index was observed between the groups.
      Serum adiponectin was lower in the ACD group when compared to control, but no
      differences were seen when comparing the ACD and RCD groups. Mesenteric
      adiponectin expression was lower in the FCD group when compared to the FC group.
      Serum leptin was similar in all groups. The lower levels of serum and mesenteric
      adiponectin in active CD suggest a defective regulation of anti-inflammatory
      pathways in CD pathogenesis.

PMID- 23121677
TI  - Reduced expression of galectin-1 and galectin-9 by leucocytes in asthma patients.
AB  - Accumulating evidence shows that galectins play roles in the initiation and
      resolution phases of inflammatory responses by promoting anti- or proinflammatory
      effects. This study investigated the presence of three members of the galectin
      family (galectin-1, -3 and -9) in induced sputum samples of asthma patients, as
      well as their possible implication in the immunopathogenesis of human asthma.
      Levels of interleukin (IL)-5, IL-13, and galectins were determined in leucocytes
      isolated from induced sputum samples by reverse transcription-polymerase chain
      reaction (RT-PCR) immunofluorescence and flow cytometry. High levels of IL-5 and
      IL-13 mRNA were detected in sputum cells from asthma patients. In parallel,
      immunoregulatory proteins galectin-1 and galectin-9 showed a reduced expression
      on macrophages from sputum samples compared with cells from healthy donors. In
      vitro immunoassays showed that galectin-1 and galectin-9, but not galectin-3, are
      able to induce the production of IL-10 by peripheral blood mononuclear cells from
      healthy donors. These findings indicate that macrophages from sputum samples of
      asthma patients express low levels of galectin-1 and galectin-9, favouring the
      exacerbated immune response observed in this disease.

PMID- 23121679
TI  - Usefulness of the delta neutrophil index for assessing neonatal sepsis.
AB  - AIM: We investigated the significance of the calculated delta neutrophil index
      (DNI) as a diagnostic factor for neonatal sepsis. METHODS: In retrospective
      study, 24 infants were diagnosed with blood culture-proven sepsis, and 48 non
      septic neonates matched for gestational age, and birth weight served as controls.
      Among the 24 infants with sepsis, 5 died within 7 days at diagnosis. RESULTS:
      Mean DNI (at diagnosis, after 24 h and 72 h), CRP and WBC counts were
      significantly higher, and neutrophil and platelet counts were significantly lower
      in sepsis group than control group. In sepsis group, mean DNI at the time of
      diagnosis, DNI at 72 h, and CRP at 72 h were significantly higher, and platelet
      counts were significantly lower for patients with sepsis who died compared with
      those who survived. In multiple logistic regression analysis, mortality in
      neonates with sepsis significantly correlated with DNI at 72 h (OR 1.47, 95% CI
      1.1-5.6, p = 0.032) and with platelet count (OR 0.93, 95% CI 0.51-0.99, p =
      0.014). ROC analysis for DNI at 72 h revealed a cut-off value of 12%, which
      predicted mortality with 81% sensitivity and 87% specificity. CONCLUSION: DNI may
      be a valuable tool in assessing the prognosis of patients with neonatal sepsis.

PMID- 23121680
TI  - Factors associated with latent tuberculosis among asylum seekers in Switzerland:
      a cross-sectional study in Vaud County.
AB  - BACKGROUND: Screening and treatment of latent tuberculosis infection (LTBI) in
      asylum seekers (AS) may prevent future cases of tuberculosis. As the screening
      with Interferon Gamma Release Assay (IGRA) is costly, the objective of this study
      was to assess which factors were associated with LTBI and to define a score
      allowing the selection of AS with the highest risk of LTBI. METHODS: In across
      sectional study, AS seekers recently arrived in Vaud County, after screening for
      tuberculosis at the border were offered screening for LTBI with T-SPOT.TB and
      questionnaire on potentially risk factors. The factors associated with LTBI were
      analyzed by univariate and multivariate regression. RESULTS: Among 393 adult AS,
      98 (24.93%) had a positive IGRA response, five of them with active tuberculosis
      previously undetected. Six factors associated with LTBI were identified in
      multivariate analysis: origin, travel conditions, marital status, cough, age and
      prior TB exposure. Their combination leads to a robust LTBI predictive score.
      CONCLUSIONS: The prevalence of LTBI and active tuberculosis in AS is high. A
      predictive score integrating six factors could identify the asylum seekers with
      the highest risk for LTBI.

PMID- 23121681
TI  - A randomized controlled trial of dabigatran versus warfarin for periablation
      anticoagulation in patients undergoing ablation of atrial fibrillation.
AB  - BACKGROUND: We aimed to evaluate the feasibility of an oral direct thrombin
      inhibitor, dabigatran, as a periprocedural anticoagulant for use with ablation of
      atrial fibrillation (AF). METHODS: Consecutive patients scheduled to undergo an
      AF ablation were randomly assigned to receive dabigatran (n = 45) or warfarin (n
      = 45) to compare their clinical feasibility. Both of those oral anticoagulants
      were discontinued the day before the ablation and were resumed after confirming
      hemostasis of the venipuncture site. A bridging therapy with heparin was not used
      in either of the patient groups. RESULTS: Dabigatran was switched to warfarin
      before the ablation because of dyspepsia in three patients. An occurrence of
      rebleeding from the venipuncture site was less common in dabigatran-allocated
      patients than in warfarin-allocated patients (20% vs 44%; P = 0.013). The
      reduction in the D-dimer level after the initiation of oral anticoagulants was
      greater in the dabigatran-allocated patients than in the warfarin-allocated
      patients. The time from the initiation of the anticoagulants to the ablation was
      significantly shorter in the dabigatran-allocated patients than in the warfarin
      allocated patients (43 +/- 7 vs 63 +/- 13 days; P < 0.0001). There was only one
      fatal periprocedural complication in a patient receiving warfarin, who had a
      mesenteric arterial thrombosis after the ablation. CONCLUSIONS: An
      anticoagulation strategy with dabigatran may surpass that with warfarin in
      reducing both the periprocedural risk of minor bleeding and a hypercoagulable
      state, and the time to ablation in patients undergoing ablation of AF.

PMID- 23121682
TI  - Improved diagnostic accuracy for neuroendocrine neoplasms using two chromogranin
      A assays: the importance of protein matrix effects.

PMID- 23121683
TI  - Effect of bone marrow mesenchymal stem cell transplant on synovial proliferation
      in rats with type II collagen-induced arthritis.
AB  - OBJECTIVES: To investigate the influence and mechanism of bone marrow mesenchymal
      stem cell transplant in the synovial proliferation of type II collagen-induced
      arthritis. MATERIALS AND METHODS: From the bone marrow of Sprague-Dawley rats,
      mesenchymal stem cells were isolated and expanded. Forty rats were randomly
      divided into 5 groups: normal control, early mesenchymal stem cell treatment,
      late mesenchymal stem cell treatment, early collagen-induced arthritis control,
      and late collagen-induced arthritis control. The mesenchymal stem cells and
      normal saline were injected through the tail vein, and the following parameters
      were observed: arthritis index, articular pathology changes, serum vascular
      endothelial growth factor level, tumor necrosis factor-?, and interluekin-17
      levels as detected through stable enzyme-linked immunosorbent assay. RESULTS: The
      arthritis index and articular pathologic scores of the early and late treatment
      groups were lower compared with those of the control groups (P < .05). The
      arthritis index and articular pathologic scores of the late treatment group were
      lower than those of the early treatment group (P < .05). The levels of vascular
      endothelial growth factor, tumor necrosis factor-alpha, and interluekin-17 of the
      early and late treatment groups were significantly decreased compared with the
      collagen-induced arthritis control groups (P < .05), and these levels were
      positively correlated with the arthritis index and articular pathologic scores (P
      < .05). CONCLUSIONS: The transplant of mesenchymal stem cells in rats with
      collagen-induced arthritis can inhibit the proliferation of synovium, which may
      be attributed to the reduced expression of vascular endothelial growth factor,
      tumor necrosis factor-alpha, and interluekin-17.

PMID- 23121684
TI  - Optimized dose of imatinib for treatment of gastrointestinal stromal tumors: a
      meta-analysis.
AB  - OBJECTIVE: To investigate the efficacy and safety of standard-dose versus high
      dose imatinib. METHODS: After a systematic review of English language articles,
      five studies including 2008 patients were eligible for the meta-analysis. Data
      extracted from each study were synthesized into overall odds ratios (OR).
      RESULTS: The overall OR for the high dose vs standard dose was 1.19 (95% CI 1.00
      1.42) and the Z-score for the overall effect was 1.93 (P = 0.054), suggesting
      that high-dose imatinib added no survival benefits. The dose-related toxicity was
      also assessed in the same way. The rates of rash, hemorrhage, nausea, vomiting
      and taste disturbance increased as dose increased (P < 0.05), whereas the
      incidence of headache, abdominal pain, edema, fatigue, anemia, infection, muscle
      cramp and constipation was nearly identical and showed no significant difference.
      CONCLUSIONS: Imatinib at a standard dose produces a similar effect to that at a
      high dose. The severity of the toxicity is associated with the dose of imatinib.
      However, larger and randomized studies are needed to draw definitive conclusions.

PMID- 23121685
TI  - Tetra-2,3-pyrazinoporphyrazines with externally appended pyridine rings. 12. New
      heteropentanuclear complexes carrying four exocyclic cis-platin-like
      functionalities as potential bimodal (PDT/cis-platin) anticancer agents.
AB  - Heteropentanuclear porphyrazines having the formula [(PtCl2)4LM] where L =
      tetrakis-2,3-[5,6-di(2-pyridyl)pyrazino]porphyrazinato dianion and M = Zn(II),
      Mg(II)(H2O), Pd(II), Cu(II) or Co(II) were characterized by elemental analyses,
      IR-UV-visible spectroscopy and electrochemistry and the data compared to new and
      previously published results for the corresponding homopentanuclear compound
      [(PtCl2)4LPt]. This latter species has four external N2(py)PtCl2 coordination
      sites which closely resemble cis-platin, (NH3)2PtCl2, the potent chemotherapeutic
      anticancer drug, and is able to act as a photosensitizer for the generation of
      (1)O2, the cytotoxic agent in photodynamic therapy (PDT). UV-visible spectra and
      half wave potentials for reduction of [(PtCl2)4LM], [(PtCl2)4LPt], the parallel
      series of mononuclear [LM] compounds and the pentanuclear [(PdCl2)4LM] compounds
      were examined in the nonaqueous solvents dimethyl sulfoxide, pyridine, and
      dimethylformamide. The complete set of available data indicate that external
      coordination of the PtCl2 and PdCl2 units significantly increases the level of
      the electron-deficiency of the entire molecular framework despite the fact that
      these groups are far away from the central porphyrazine pi-ring system and have
      coordination sites nearly orthogonal to the plane of the macrocycle. The
      pentanuclear species [(M'Cl2)4LM] (M' = Pt(II), Pd(II)) undergo multiple one
      electron transfers and exhibit an easier reducibility as compared to related
      electrode reactions of the parent compounds [LM] having the same central metal.
      Aggregation phenomena and reducibility of the porphyrazines to their monoanionic
      form (prevalently in DMF) are observed for some of the examined compounds and
      were analyzed and accurately taken into account. Quantum yields of (1)O2
      (PhiDelta), of interest in PDT, were measured for [(PtCl2)4LM] with M = Zn(II),
      Mg(II)(H2O), or Pd(II) and the related macrocycles [(PdCl2)4LM] and [LM] in
      dimethylformamide (DMF) and/or DMF preacidified with HCl (DMF/HCl, [HCl]: 1-2 *
      10(-4) M). Excellent PhiDelta values (0.5-0.6) which qualify the compounds as
      potent photosensitizers in PDT were obtained for the pentanuclear species having
      Zn(II) or Pd(II) as central metal ions. The [(PtCl2)4LZn] and [(PtCl2)4LPd]
      complexes are of special interest as potential bimodal anticancer agents because
      of the incorporated four cis-platin-like functionalities. 

PMID- 23121686
TI  - Quantitative bead-based assay for detection of JAK2 exon 12 mutations.

PMID- 23121687
TI  - Single-molecule sensing using carbon nanotubes decorated with magnetic clusters.
AB  - First-principles and nonequilibrium Green's function techniques are used to
      investigate magnetism and spin-polarized quantum transport in metallic carbon
      nanotubes (CNT) decorated with transition metal (Ni(13), Pt(13)) magnetic
      nanoclusters (NC). For small cluster sizes, the strong CNT-NC interaction induces
      spin-polarization in the CNT. The adsorption of a benzene molecule is found to
      drastically modify the CNT-NC magnetization. Such a magnetization change should
      be large enough to be detected via magnetic-AFM or SQUID magnetometry, hence
      suggesting a novel approach for single-molecule gas detection.

PMID- 23121688
TI  - Left ventricular function in acute inflammatory peri-myocardial diseases - new
      insights and long-term follow-up.
AB  - BACKGROUND: Until recently acute inflammatory peri-myocardial syndromes have been
      associated with global rather regional left ventricular (LV) dysfunction. Recent
      advances in cardiac imaging with echocardiographic techniques and magnetic
      resonance imaging (MRI) permit comprehensive evaluation of global and regional LV
      function. Our study was aimed to assess regional LV function in 100 patients with
      acute perimyocarditis, and correlate these findings with the clinical
      presentation. METHODS: We report on 100 patients with acute perimyocarditis
      admitted during 2008-2011, in whom LV function was assessed by semi-quantitative
      wall motion score analysis on conventional echo. Long-term mortality and
      recurrent hospitalization were also assessed. RESULTS: Wall motion score in 100
      patients with acute perimyocarditis demonstrated a significant predominance of
      regional wall motion abnormalities in the infero-postero-lateral LV wall. These
      data correspond well with speckle tracking results of a subgroup of these
      patients published earlier. Recent MRI data show frequent late enhancement of
      contrast in the infero-lateral region of the LV in patients with perimyocarditis.
      These observations were useful in re-classification of our patients into one of
      the following groups: pure or predominant pericarditis, and pure or predominant
      myocarditis. Over a mean period of 37 months, there was no mortality. Though
      recurrent hospitalizations were rather frequent, no significant differences were
      observed among groups. CONCLUSIONS: Regional wall motion abnormalities in the
      infero-postero-lateral segments of the LV are frequent in patients with acute
      perimyocarditis. Detailed echocardiographic examination early in the course of
      the disease should become a major factor in the clinical differentiation among
      the various clinical presentations of acute inflammatory peri-myocardial
      syndromes. The long-term outcome of these patients appears to be benign, though
      recurrent hospitalizations are not infrequent.

PMID- 23121690
TI  - Tumor vasculature: the Achilles' heel of cancer?
AB  - INTRODUCTION: Tumor-associated angiogenesis is one of the essential hallmarks
      underlying cancer development and metastasis. Anti-angiogenic agents accordingly
      aim to restrain cancer progression by blocking the formation of new vessels,
      improving the delivery of chemotherapeutic agents to the tumor site and reducing
      the shedding of metastatic cells into the circulation. This review article
      addresses some key issues in the use of angiogenesis inhibitors in cancer. AREAS
      COVERED: The authors review the complex interactions between cell signaling
      pathways involved in tumor angiogenesis, and focus in particular on the molecular
      mechanisms that may induce resistance to angiogenesis inhibitors. They will also
      discuss some novel therapeutic strategies evolving within anti-angiogenic therapy
      such as the targeting of VEGFR-3, endothelial integrins and hepatocyte growth
      factor-MET signaling. EXPERT OPINION: Although anti-angiogenic therapy is
      targeted at the non-malignant part of the tumor, the intricate network of growth
      promoting signaling pathways and in particular the redundancy when single
      pathways are targeted in endothelial cells represents a major therapeutic
      obstacle. A key challenge will be to develop more efficient inhibitors, combined
      with an individualized approach based on each tumor's own endothelial signaling
      profile. Furthermore, reliable biomarkers which pinpoint those patients that will
      benefit from anti-angiogenic therapy need to be identified.

PMID- 23121689
TI  - A translocator-specific export signal establishes the translocator-effector
      secretion hierarchy that is important for type III secretion system function.
AB  - Type III secretion systems are used by many Gram-negative pathogens to directly
      deliver effector proteins into the cytoplasm of host cells. To accomplish this,
      bacteria secrete translocator proteins that form a pore in the host-cell membrane
      through which the effector proteins are then introduced into the host cell.
      Evidence from multiple systems indicates that the pore-forming translocator
      proteins are exported before effectors, but how this secretion hierarchy is
      established is unclear. Here we used the Pseudomonas aeruginosa translocator
      protein PopD as a model to identify its export signals. The N-terminal secretion
      signal and chaperone, PcrH, are required for export under all conditions. Two
      novel signals in PopD, one proximal to the chaperone binding site and one at the
      very C-terminus of the protein, are required for export of PopD before effector
      proteins. These novel export signals establish the translocator-effector
      secretion hierarchy, which in turn, is critical for the delivery of effectors
      into host cells.

PMID- 23121691
TI  - The mQTL hotspot on linkage group 16 for phenolic compounds in apple fruits is
      probably the result of a leucoanthocyanidin reductase gene at that locus.
AB  - BACKGROUND: Our previous study on ripe apples from a progeny of a cross between
      the apple cultivars 'Prima' and 'Fiesta' showed a hotspot of mQTLs for phenolic
      compounds at the top of LG16, both in peel and in flesh tissues. In order to find
      the underlying gene(s) of this mQTL hotspot, we investigated the expression
      profiles of structural and putative transcription factor genes of the
      phenylpropanoid and flavonoid pathways during different stages of fruit
      development in progeny genotypes. RESULTS: Only the structural gene
      leucoanthocyanidin reductase (MdLAR1) showed a significant correlation between
      transcript abundance and content of metabolites that mapped on the mQTL hotspot.
      This gene is located on LG16 in the mQTL hotspot. Progeny that had inherited one
      or two copies of the dominant MdLAR1 alleles (Mm, MM) showed a 4.4- and 11.8-fold
      higher expression level of MdLAR1 respectively, compared to the progeny that had
      inherited the recessive alleles (mm). This higher expression was associated with
      a four-fold increase of procyanidin dimer II as one representative metabolite
      that mapped in the mQTL hotspot. Although expression level of several structural
      genes were correlated with expression of other structural genes and with some MYB
      and bHLH transcription factor genes, only expression of MdLAR1 was correlated
      with metabolites that mapped at the mQTL hotspot. MdLAR1 is the only candidate
      gene that can explain the mQTL for procyanidins and flavan-3-ols. However, mQTLs
      for other phenylpropanoids such as phenolic esters, dihydrochalcones and
      flavonols, that appear to map at the same locus, have so far not been considered
      to be dependent on LAR, as their biosynthesis does not involve LAR activity. An
      explanation for this phenomenon is discussed. CONCLUSIONS: Transcript abundances
      and genomic positions indicate that the mQTL hotspot for phenolic compounds at
      the top of LG16 is controlled by the MdLAR1 gene. The dominant allele of the
      MdLAR1 gene, causing increased content of metabolites that are potentially health
      beneficial, could be used in marker assisted selection of current apple breeding
      programs and for cisgenesis.

PMID- 23121693
TI  - Photoshrinkage in polysaccharide gels with trivalent metal ions.
AB  - The giant anionic polysaccharide "sacran", which is composed of 6-deoxyhexoses,
      pentoses, uronic acids as well as hexoses, showed hydrophobization and
      insolubilization phenomena in response to ultraviolet light irradiation. The
      sacran solution became turbid, and microparticles were formed by
      photoirradiation. To visualize the results of this photoreaction, anionic
      polysaccharide gels cross-linked by metal cations were used. As a result, we
      observed that sacran-gels with trivalent metal ions gradually contracted
      depending on the photoirradiation energy. In contrast, alginate gels used as a
      comparison degraded instead of contracting. This photoshrinkage of the sacran
      gels may be attributed to the hydrophobization of uronic acid based on
      photodecarboxylation. We propose that sacran-metal ion gels can function as
      effective, photoresponsive gels.

PMID- 23121692
TI  - alpha-Aryl-substituted allenamides in an imino-Nazarov cyclization cascade
      catalyzed by Au(I).
AB  - An imino-Nazarov cyclization using alpha-aryl-substituted allenamides is
      described. This gold(I)-catalyzed cascade is efficient and regioselective in
      constructing a diverse array of synthetically useful aromatic-ring fused
      cyclopentenamides. The success in this transformation represents a solution to
      the challenge in establishing an imino-Nazarov cyclization process.

PMID- 23121694
TI  - Molecular modeling of different substrate-binding modes and their role in
      penicillin acylase catalysis.
AB  - Molecular modeling was addressed to understand different substrate-binding modes
      and clarify the role of two positively charged residues of the penicillin G
      acylase active site - betaR263 and alphaR145 - in binding of negatively charged
      substrates. Although the electrostatic contribution to productive substrate
      binding was dominated by betaR263 rather than alphaR145, it was found that
      productive binding was not the only possible mode of substrate placement in the
      active site. Two extra binding modes - nonproductive and preproductive - were
      located by means of molecular docking and dynamics with binding affinities
      comparable with the productive one. A unique feature of nonproductive and
      preproductive complexes was that the substrate's acyl group did not penetrate the
      hydrophobic pocket, but occupied a patch on the protein interface spanning from
      betaR263 to alphaR145. Nonproductive and preproductive complexes competed with
      each other and productive binding mode, giving rise to increased apparent
      substrate binding. Preproductive complex revealed an ability to switch to a
      productive one during molecular dynamics simulations, and conformational
      plasticity of the penicillin G acylase active site was shown to be crucial for
      that. Nonproductive binding observed at molecular modeling corresponded well with
      experimentally observed substrate inhibition in penicillin acylase catalysis. By
      combining estimated free energies of substrate binding in each mode, and
      accounting for two possible conformations of the penicillin G acylase active site
      (closed and open) quantitative agreement with experimentally measured K(M) values
      was achieved. Calculated near-attack conformation frequencies from corresponding
      molecular dynamics simulations were in a quantitative correlation with
      experimental k(cat) values and demonstrated adequate application of molecular
      modeling methods.

PMID- 23121695
TI  - Utility of right ventricular strain imaging in predicting pulmonary vascular
      resistance in patients with pulmonary hypertension.
AB  - Pulmonary vascular resistance (PVR) has important prognostic implications in the
      assessment of patients with pulmonary hypertension. Using echocardiography to
      measure PVR would have the advantage of being able to follow patients serially
      and to assess their response to treatment noninvasively. The authors sought to
      assess whether right ventricular strain rate imaging (SRI) can predict PVR in
      patients with pulmonary hypertension. The study population consisted of 46
      patients referred for right heart catheterization. The inclusion criteria was
      mean pulmonary artery pressure >=25 mm Hg in right heart catheterization in
      patients with pulmonary hypertension including chronic systolic heart failure.
      Echocardiography was performed to obtain SRI just before right heart
      catheterization. Mean values of peak systolic longitudinal strain and strain rate
      obtained from basal and mid-right ventricular free wall were calculated. The
      control group consisted of 35 healthy adults matched for age and sex. The most
      significant correlations were between basal right ventricular strain and strain
      rate (SR) and mean pulmonary arterial pressure (r=0.63, P=.000), transpulmonary
      gradient (r=0.6, P=.001), and PVR (r=0.5, P=.003). SR was independently
      correlated with PVR (PVR=26.9-16.9*basal right ventricular SR; r=0.53, P=.003).
      The present study shows that basal right ventricular free wall strain and SR
      could be independently correlated with PVR in patients with pulmonary
      hypertension.

PMID- 23121696
TI  - The roles of livestock in developing countries.
AB  - Livestock play a significant role in rural livelihoods and the economies of
      developing countries. They are providers of income and employment for producers
      and others working in, sometimes complex, value chains. They are a crucial asset
      and safety net for the poor, especially for women and pastoralist groups, and
      they provide an important source of nourishment for billions of rural and urban
      households. These socio-economic roles and others are increasing in importance as
      the sector grows because of increasing human populations, incomes and
      urbanisation rates. To provide these benefits, the sector uses a significant
      amount of land, water, biomass and other resources and emits a considerable
      quantity of greenhouse gases. There is concern on how to manage the sector's
      growth, so that these benefits can be attained at a lower environmental cost.
      Livestock and environment interactions in developing countries can be both
      positive and negative. On the one hand, manures from ruminant systems can be a
      valuable source of nutrients for smallholder crops, whereas in more industrial
      systems, or where there are large concentrations of animals, they can pollute
      water sources. On the other hand, ruminant systems in developing countries can be
      considered relatively resource-use inefficient. Because of the high yield gaps in
      most of these production systems, increasing the efficiency of the livestock
      sector through sustainable intensification practices presents a real opportunity
      where research and development can contribute to provide more sustainable
      solutions. In order to achieve this, it is necessary that production systems
      become market-orientated, better regulated in cases, and socially acceptable so
      that the right mix of incentives exists for the systems to intensify. Managing
      the required intensification and the shifts to new value chains is also essential
      to avoid a potential increase in zoonotic, food-borne and other diseases. New
      diversification options and improved safety nets will also be essential when
      intensification is not the primary avenue for developing the livestock sector.
      These processes will need to be supported by agile and effective public and
      private institutions.

PMID- 23121697
TI  - Isolated peripancreatic tuberculous lymphadenopathy: a rare manifestation of
      abdominal tuberculosis mimicking pancreatic cystic neoplasm.

PMID- 23121698
TI  - [Use of glaucoma medications during pregnancy and breastfeeding].

PMID- 23121699
TI  - [Diabetic retinopathy screening and teleophthalmology].
AB  - OBJECTIVE: To determine the prevalence of diabetic retinopathy (DR) and evaluate
      our experience in DR screening in a study carried out between the Ophthalmology
      Department of the University General Hospital of Alicante and Department 19
      Primary Care of Alicante by using a non-retinal mydriatic camera and
      telemedicine. MATERIAL AND METHODS: A descriptive, cross-sectional study was
      conducted on 2,435 diabetic patients from 1 February 2006 to 1 February 2009.
      Three 45 degrees  retinographies of both eyes of each patient were obtained and
      sent to the Department of Ophthalmology via the hospital intranet. These were
      then evaluated by 2 ophthalmologists, experts in the retina, with each issuing an
      individualized report for each patient. RESULTS: The prevalence of DR was 17.90%,
      with 80.73% of them having mild-moderate proliferative DR, 12.16% severe non
      proliferative DR, 2.29% proliferative DR, and 4.82% with diabetic maculopathy
      associated with any level of retinopathy. The retinographies were considered low
      quality in 41 patients (1.69%). CONCLUSIONS: We highlight the benefits of the
      tele-ophthalmology in screening diabetic patients to enable early diagnosis and
      treatment, and improving the circuit of communication between primary and
      specialist care.

PMID- 23121700
TI  - [Intracameral bevacizumab (Avastin(r)) in the management of neovascular glaucoma
      surgery].
AB  - PURPOSE: To describe a case series of neovascular glaucoma treated with
      intracameral bevacizumab prior to filtering surgery. DESIGN: Descriptive,
      retrospective case series. METHODS: Five eyes of 5 patients with neovascular
      glaucoma due to any cause candidates to filtering surgery who had previously
      received an injection of intracameral bevacizumab (1.25 mg/0.05 ml) as treatment
      for neovascularization of anterior chamber. Results observed one week and 4 weeks
      postsurgery are reported. RESULTS: Bevacizumab produced regression of the angle
      neovascularization and the intraocular pressure. Only one case of postoperative
      bleeding was detected. CONCLUSIONS: Intracameral bevacizumab prior to filtering
      surgery of neovascular glaucoma diminished the neovascularization and intraocular
      pressure after 4 weeks of its administration and was effective in preventing
      intraoperative and postoperative bleeding. It also constitutes a promising way of
      investigation to prevent surgical complications.

PMID- 23121701
TI  - [Comparison of dynamic contour tonometry, Goldmann and pneumotonometer in ocular
      hypertension patients and their relationship to pachymetry and ocular pulse
      amplitude].
AB  - PURPOSE: To determine the relationship between dynamic contour tonometry (DCT),
      Goldmann applanation tonometry (GAT) and pneumotonometry (PNT) in ocular
      hypertension patients (OHT) and their relationship to central corneal thickness
      (CCT) and ocular pulse amplitude (OPA). METHODS: Sixty patients (101 eyes) with
      intraocular pressure (IOP) >=21 mmHg using GAT and normal appearing optic nerve
      heads and normal visual fields were included. The following tests were performed
      simultaneously during a single visit: IOP using DCT, GAT and PNT, OPA using DCT
      and CCT using ultrasound pachymetry. We studied the difference IOP between these
      3 tonometers using Wilcoxon non-parametric test and the effect of CCT on IOP and
      OPA, as well as the relationship between OPA and IOP using Spearman correlation
      coefficient. RESULTS: The median PNT IOP was 24 mmHg (Inter-quartile range [IQR]:
      22-26), median GAT IOP was 22 mmHg (IQR: 22-24), and median DCT IOP was 28.2 mmHg
      (IQR: 24.1-30.7). PNT and DCT had higher IOP values than GAT (median 2 mmHg and
      6.2 mmHg, respectively). Mean CCT was 594.5 MUm (SD 30.0). GAT IOP and DCT IOP
      showed an increase with increased corneal thickness (r:0.209; P=.036 and r:0.195;
      P=.051, respectively). PNT IOP did not change with CCT (r:0.15; P=.12). The
      median OPA was 4.8 mmHg (IQR: 3.6-6.1), and significantly increased with GAT IOP
      (r:0,38; P<.001) and with CCT (r:0.287; P=.004). This association was unclear
      with IOP PNT and IOP DCT (r:0.067; P=.50 and r:0,17, P=.08, respectively).
      CONCLUSIONS: DCT and PNT IOP values were higher than GAT IOP measurements in
      ocular hypertension patients. GAT IOP showed a significant increase with
      increased corneal thickness. Increased OPA seems to correlate with increased CCT
      and IOP, particularly if GAT is used.

PMID- 23121702
TI  - [Transepithelial phototherapeutic keratectomy to treat chronic laser in situ
      keratomileusis-flap macrostriae. A case review].
AB  - OBJECTIVE: To describe the use of transepithelial phototherapeutic keratecomy for
      the long-term treatment of post-laser in situ keratomileusis (LASIK) flap
      macrostriae. METHOD: We present the case of a 22 year old male with visual loss
      in the left eye due to chronic flap macrostriae that was treated with
      transepithelial PTK. RESULTS: Striae and haze were no longer visible, with a
      significant improvement of best corrected visual acuity. Refraction in the third
      month was +9.75-4.00*170 degrees . A phakic intraocular lens was implanted one
      year later with an uncorrected visual acuity of 0.8. CONCLUSIONS: PTK can solve
      chronic flap striae, but refraction outcome is unpredictable.

PMID- 23121703
TI  - [Propranolol: Treatment of capillary hemangioma with orbital involvement].
AB  - CLINICAL CASE: A 2-months-old girl had a fast growth hemangioma in the left side
      of the face, that involved upper eyelid and superior and external portion of the
      orbit, covering her visual axis and pushing the eye and lateral rectus muscle. We
      gave oral propranolol as treatment and we noticed a fast and constant hemangioma
      reduction and resolution of orbital and palpebral component. DISCUSSION:
      According to previous researches, propranolol seems to be an effective and safe
      drug to treat capillary hemangioma. In our case, response to propranolol was
      satisfactory and with no side effects. This treatment should be considered as a
      promising alternative.

PMID- 23121704
TI  - [Ocular electrophysiology].

PMID- 23121705
TI  - [Crede's prophylaxis].

PMID- 23121706
TI  - [Eye pathology in the paintings by Rafael Sanzio (III). The Transfiguration].

PMID- 23121707
TI  - [Behaviour disorder as a presentation of fat embolism syndrome].

PMID- 23121708
TI  - [Intrauterine myelomeningocele repair: experience of the fetal medicine and
      therapy program of the Virgen de Rocio University Hospital].
AB  - The most frequent form of spina bifida is myelomeningocele. There is no optimal
      postnatal treatment for this defect. In addition to the motor or sensory
      deficits, which depend on the location of the lesion, the defect is usually
      associated with Chiari ii malformation in affected children. Myelomeningocele has
      high mortality and, in up to 80% to 90% of patients, can be accompanied by
      hydrocephalus, which causes severe neurocognitive impairment and requires the
      patient to be shunted for survival. Intrauterine repair of fetal malformations
      employing open access through hysterotomy has become a therapeutic option due to
      improved anesthetic and surgical techniques and instrumentation, which have
      allowed this type of intervention to become relatively frequent. Anesthetic
      treatment should focus on both the mother and fetus and the hemodynamic factors
      regulating placental flow, uterine dynamics, blood loss and fetal well-being must
      remain well-controlled. Within our Program for Fetal Medicine and Therapy, 21
      open fetal interventions have been performed: 17 EXIT procedures and 4 procedures
      for the intrauterine correction of fetal myelomeningocele. We describe our
      experience of the intrauterine repair of fetal myelomeningocele through open
      fetal surgery.

PMID- 23121709
TI  - [Clinical relevance of cardiopulmonary reflexes in anesthesiology].
AB  - The baroreflex, chemoreflex, pulmonary reflexes, Bezold-Jarisch and Bainbridge
      reflexes and their interaction with local mechanisms, are a demonstration of the
      richness of cardiovascular responses that occur in human beings. As well as
      these, the anesthesiologist must contend with other variables that interact by
      attenuating or accentuating cardiopulmonary reflexes such as, anesthetic drugs,
      surgical manipulation, and patient positioning. In the present article we review
      these reflexes and their clinical relevance in anesthesiology. 

PMID- 23121710
TI  - Infants' perception of chasing.
AB  - Two significant questions in cognitive and developmental science are first,
      whether objects and events are selected for attention based on their features
      (featural processing) or the configuration of their features (configural
      processing), and second, how these modes of processing develop. These questions
      have been addressed in part with experiments focused on infants' perception of
      faces, human body shapes, and biological motion of individual agents. Here, we
      investigate 4- and 10-month-old infants' (N=192) attention to social motions,
      specifically to chasing-a ubiquitous, ancient, and fitness-relevant mode of
      interaction. We constructed computer-generated animations of chasing that had
      three properties: acceleration, high turning rates, and attraction ("heat
      seeking"). In the first experiment we showed chasing side-by-side with a control
      display of inanimate, billiard-ball-like motions. Infants strongly preferred
      attending to chasing. In the next three studies, we systematically investigated
      the effect of each property in turn (acceleration, turning, and attraction) by
      showing a display of that property side-by-side with the control display. Infants
      preferentially attended to acceleration, and to attraction, but not to turning.
      If infants preferred chasing for its configuration, then the sum of the effect
      sizes of individual properties should be smaller than their combined effects.
      That is not what we found: instead, on three measures of visual behavior, the
      summed effects of individual properties equaled (or exceeded) that of chasing.
      Moreover, although attraction drew little attention and turning no attention at
      all, acceleration drew (nearly) as much attention as chasing. Our results thus
      provide evidence that infants preferred chasing because of its features, not its
      configuration.

PMID- 23121711
TI  - "Bouba" and "Kiki" in Namibia? A remote culture make similar shape-sound matches,
      but different shape-taste matches to Westerners.
AB  - Western participants consistently match certain shapes with particular speech
      sounds, tastes, and flavours. Here we demonstrate that the "Bouba-Kiki effect", a
      well-known shape-sound symbolism effect commonly observed in Western
      participants, is also observable in the Himba of Northern Namibia, a remote
      population with little exposure to Western cultural and environmental influences,
      and who do not use a written language. However, in contrast to Westerners, the
      Himba did not map carbonation (in a sample of sparkling water) onto an angular
      (as opposed to a rounded) shape. Furthermore, they also tended to match less
      bitter (i.e., milk) chocolate samples to angular rather than rounded shapes; the
      opposite mapping to that shown by Westerners. Together, these results show that
      cultural-environmental as well as phylogenetic factors play a central role in
      shaping our repertoire of crossmodal correspondences.

PMID- 23121712
TI  - Rule learning over consonants and vowels in a non-human animal.
AB  - Perception studies have shown similarities between humans and other animals in a
      wide array of language-related processes. However, the components of language
      that make it uniquely human have not been fully identified. Here we show that
      nonhuman animals extract rules over speech sequences that are difficult for
      humans. Specifically, animals easily learn rules over both consonants and vowels,
      while humans do it only over vowels. In Experiment 1, rats learned a rule
      implemented over vowels in CVCVCV nonsense words. In Experiment 2, rats learned
      the rule when it was implemented over the consonants. In both experiments, rats
      generalized such knowledge to novel words they had not heard before. Using the
      same stimuli, human adults learned the rules over the vowels but not over the
      consonants. These results suggest differences between humans and animals on
      speech processing might lie on the constraints they face while extracting
      information from the signal.

PMID- 23121713
TI  - Activity concentration and radiological impact assessment of 226Ra, 228Ra and 40K
      in drinking waters from (OML) 30, 58 and 61 oil fields and host communities in
      Niger Delta region of Nigeria.
AB  - This paper presents the concentrations of naturally occurring radionuclides
      ((226)Ra, (228)Ra and (40)K) measured in hand dug wells, boreholes and river
      waters collected from three oil mineral leases (OML) 30, 58 & 61 oil and gas
      fields onshore of the Niger delta, using gamma spectroscopy. Fifty-four water
      samples from the three sources of drinking water supply were collected within the
      oil fields and host communities and three water samples from a control site. The
      results showed average activity concentrations of (226)Ra, (228)Ra and (40)K as
      8.9 +/- 1.0, 8.1 +/- 0.9 and 39.8 +/- 3.3 respectively for hand dug wells, 4.4 +/
      0.8, 4.6 +/- 0.5 and 28.5 +/- 3.0 for borehole water and 8.2 +/- 1.0, 6.7 +/-
      0.7 and 32.1 +/- 3.5 for river water respectively. These (226)Ra, (228)Ra and
      (40)K average are well above the WHO permissible levels of 1.0, 0.1 and 10 BqL(
      1) respectively and also above the control values. Although the hazard indices
      calculated are still within their tolerable levels, the estimated committed
      effective dose due to intake of the sampled water for all the four age groups
      considered are far above the ICPR 0.1 mSvyr(-1) maximum permissible limit. The
      result indicates some level of water pollution in the studied area.

PMID- 23121714
TI  - Biopolymer-encapsulated protein microcapsules spontaneously formed at the ionic
      liquid-water interface.
AB  - Aqueous microdroplets introduced in ionic liquids (ILs) provide unique interfaces
      where surface-modified protein microcapsules are spontaneously formed at systemic
      temperature. The susceptibility of proteins to form microcapsules at the water-IL
      microinterface depends on protein species and is related to the number of charged
      residues exhibited on protein surfaces. When both of the capsule-forming (host)
      proteins and guests biopolymers such as nucleic acids or enzymes are introduced
      in the aqueous microdroplets, microcapsules are formed selectively from host
      proteins while the guest biopolymers remain encapsulated in the aqueous pool.
      Microcapsules formed in the IL phase are facilely extracted to aqueous phase
      after consecutive cross-linking and surface modification reactions, and the whole
      processes can be done in one pot. Enzymes confined in the inner water phase of
      aqueous protein microcapsules showed innate activity, as visualized by site
      specific fluorescence detection using confocal laser scanning microscopy (CLSM).
      The present IL-water interfacial synthesis of protein microcapsules eliminates
      the use of volatile organic solvents or solid colloid templates, which creates a
      much-coveted solution to existing technologies.

PMID- 23121715
TI  - Patients' perceptions of their "most" and "least" important medications: a
      retrospective cohort study.
AB  - BACKGROUND: Despite benefits of adherence, little is known about the degree to
      which patients will express their perceptions of medications as more or less
      important to take as prescribed. We determined the frequency with which Veteran
      patients would explicitly identify one of their medications as "most important"
      or "least important." FINDINGS: We conducted a retrospective cohort study of
      patients from ambulatory clinics at VA Boston from April 2010-July 2011. Patients
      answered two questions: "Which one of your medicines, if any, do you think is the
      most important? (if none, please write 'none')" and "Which one of your medicines,
      if any, do you think is the least important? (if none, please write 'none')." We
      determined the prevalence of response categories for each question. Our cohort of
      104 patients was predominantly male (95%), with a mean of 9 medications (SD 5.7).
      Regarding their most important medication, 41 patients (39%) identified one
      specific medication; 26 (25%) selected more than one; 21 (20%) wrote "none"; and
      16 (15%) did not answer the question. For their least important medication, 31
      Veterans (30%) chose one specific medication; two (2%) chose more than one; 51
      (49%) wrote "none"; and 20 (19%) did not directly answer the question.
      CONCLUSIONS: Thirty-five percent of patients did not identify a most important
      medication, and 68% did not identify a least important medication. Better
      understanding of how patients prioritize medications and how best to elicit this
      information will improve patient-provider communication, which may in turn lead
      to better adherence.

PMID- 23121716
TI  - Evaluation of the transmission of porcine circovirus type 2 (PCV-2) genogroups a
      and b with semen from infected specific-pathogen-free boars.
AB  - The porcine circovirus type 2 (PCV-2) is associated with several diseases
      including reproductive failure. This syndrome has been experimentally reproduced
      twice with two PCV-2 isolates representative of each major PCV-2 genogroup, i.e.
      PCV-2a and PCV-2b (Cariolet et al., 2002; Rose et al., 2007). In these two
      previous studies, the sows were infected by intra-uterine inoculation at
      insemination with 10(4.3) and 10(3.18) TCID(50) of PCV-2a and PCV-2b,
      respectively, corresponding to 1.2 * 10(11) and 3 * 10(10) genome copies,
      respectively. The aim of this present study was to quantify viral shedding in
      semen from specific-pathogen-free (SPF) boars infected with isolates from the two
      major PCV-2 genogroups a and b. We studied the transmission of the PCV-2 virus
      through contaminated semen to SPF sows and their offspring. The four inoculated
      boars developed sub-clinical PCV-2 infections and PCV-2 genomes were occasionally
      detected in semen after nasal infection of boars, with up to 1.2 * 10(6)copies/mL
      in the sperm-rich fraction. When PCV-2-contaminated semen was inoculated in SPF
      sows at artificial insemination, the sows and their offspring did not show any
      signs of PCV-2 infection or PCV-2 antibodies or genomes. In the present study,
      sows were inoculated with a maximal dose of 1.7 * 10(7) viral genome copies,
      which is lower than the genomic loads (i.e. 1.2 * 10(11) and 3 * 10(10) genome
      copies) that have been shown to induce reproductive troubles in intra-uterine
      inoculated sows. Our results together with the previous experiment findings
      suggest that PCV-2-induced reproductive disorders depend on the infectious dose
      inoculated to sows by the intra-uterine route.

PMID- 23121717
TI  - A candidate gene approach to identify modifiers of the palatal phenotype in
      22q11.2 deletion syndrome patients.
AB  - OBJECTIVE: Palatal anomalies are one of the identifying features of 22q11.2
      deletion syndrome (22q11.2DS) affecting about one third of patients. To identify
      genetic variants that increase the risk of cleft or palatal anomalies in
      22q11.2DS patients, we performed a candidate gene association study in 101
      patients with 22q11.2DS genotyped with the Affymetrix genome-wide human SNP array
      6.0. METHODS: Patients from Children's Hospital of Philadelphia, USA and
      Wilhelmina Children's Hospital Utrecht, The Netherlands were stratified based on
      palatal phenotype (overt cleft, submucosal cleft, bifid uvula). SNPs in 21
      candidate genes for cleft palate were analyzed for genotype-phenotype
      association. In addition, TBX1 sequencing was carried out. Quality control and
      association analyses were conducted using the software package PLINK. RESULTS:
      Genotype and phenotype data of 101 unrelated patients (63 non-cleft subjects
      (62.4%), 38 cleft subjects (37.6%)) were analyzed. A Total of 39 SNPs on 10 genes
      demonstrated a p-value <=0.05 prior to correction. The most significant SNPs were
      found on FGF10. However none of the SNPs remained significant after correcting
      for multiple testing. CONCLUSIONS: Although these results are promising, analysis
      of additional samples will be required to confirm that variants in these regions
      influence risk for cleft palate or palatal anomalies in 22q11.2DS patients.

PMID- 23121718
TI  - Health-related quality of life and needs of care and support of adult Tanzanians
      with cancer: a mixed-methods study.
AB  - BACKGROUND: Cancer is among the three leading causes of death in low income
      countries and the highest increase with regard to incidence figures for cancer
      diseases are found in these countries. This is the first report of the health
      related quality of life (HRQOL) and needs of care and support of adult Tanzanians
      with cancer. METHODS: A mixed-methods design was used. The study was conducted at
      Ocean Road Cancer Institute (ORCI) in Dar es Salaam, Tanzania. One hundred and
      one patients with a variety of cancer diagnoses treated and cared for at ORCI
      answered the Kiswahili version of the EORTC QLQ-C30 investigating HRQOL. Thirty
      two of the patients participated in focus group interviews discussing needs of
      care and support. Data from focus group interviews were analyzed with content
      analysis. RESULTS: The findings show that the patients, both women and men,
      report a low quality of life, especially with regard to physical, role, and
      social function and a high level of symptoms and problems especially with
      financial difficulties and pain. Financial difficulties are reported to a
      remarkably high extent by both women and men. The patients, both women and men
      report least problems with emotional function. A content analysis of the
      interview data revealed needs of food and water, hygienic needs, emotional needs,
      spiritual needs, financial needs, and needs of closeness to cancer care and
      treatment services. CONCLUSION: The high score for pain points out that ORCI is
      facing severe challenges regarding care and treatment. However, when considering
      this finding it should be noted that the pain subscale of the Kiswahili version
      of the EORTC QLQ-C30 did not reach acceptable internal consistency and showed
      less than satisfactory convergent validity. This also applies to the subscales
      cognitive function and global health/quality of life. Attention should be drawn
      to meet the identified needs of Tanzanian cancer patients while hospitalized but
      also when at home. Increased accessibility of mosquito nets, pads, and pain
      killers would help to fulfil some needs.

PMID- 23121719
TI  - Structural characterization of the second intra-discal loop of the photoreceptor
      tetraspanin RDS.
AB  - Vertebrate photoreceptors contain a unique tetraspanin protein known as 'retinal
      degeneration slow' (RDS). Mutations in the RDS gene have been identified in a
      variety of human retinal degenerative diseases, and more than 70% of these
      mutations are located in the second intra-discal (D2) loop, highlighting the
      importance of this region. Here we examined the conformational and thermal
      stability properties of the D2 loop of RDS, as well as interactions with ROM-1, a
      non-glycosylated homolog of RDS. The RDS D2 loop was expressed in Escherichia
      coli as a fusion protein with maltose binding protein (MBP). The fusion protein,
      referred to as MBP-D2, was purified to homogeneity. Circular dichroism
      spectroscopy showed that the wild-type (WT) D2 loop consists of approximately 21%
      alpha-helix, approximately 20% beta-sheet and approximately 59% random coil. D2
      loop fusion proteins carrying disease-causing mutations in RDS (e.g. R172W,
      C214S, N244H/K) were also examined, and conformational changes were observed
      (compared to wild-type D2). In particular, the C150S, C214S and N244H proteins
      showed significant reductions in alpha-helicity. However, the thermal stability
      of the mutants was unchanged compared to wild-type, and all the mutants were
      capable of interacting with ROM-1, indicating that this functional aspect of the
      isolated D2 loop remained intact in the mutants despite the observed
      conformational changes. An I-TASSER model of the RDS D2 loop predicted a
      structure consistent with the circular dichroism experiments and the structure of
      the conserved region of the D2 loop of other tetraspanin family members. These
      results provide significant insight into the mechanism of RDS complex formation
      and the disease process underlying RDS-associated retinal degeneration.

PMID- 23121721
TI  - Synthesis of 1,4-bis(indolin-1-ylmethyl)benzene derivatives and their structure
      activity relationships for the interaction of human carbonic anhydrase isoforms I
      and II.
AB  - Several 1,4-bis(indolin-1-ylmethyl)benzene-based compounds containing
      substituents such as five, six and seven cyclic derivatives on indeno part (9a-c)
      were prepared and tested against two members of the pH regulatory enzyme family,
      carbonic anhydrase (CA). The inhibitory potencies of the compounds at the human
      isoforms hCA I and hCA II targets were analyzed and KI values were calculated. KI
      values of compounds for hCA I and hCA II human isozymes were measured in the
      range of 39.3-42.6MUM and 0.17-0.29MUM, respectively. The structurally related
      compound indole was also tested in order to understand the structure-activity
      relationship. Most of the compounds showed good CA inhibitory efficacy. In silico
      docking studies of these derivatives within hCA I and II were also carried out
      and results are supported the kinetic assays.

PMID- 23121720
TI  - Characterization of methicillin-susceptible and -resistant staphylococci in the
      clinical setting: a multicentre study in Nigeria.
AB  - BACKGROUND: The staphylococci are implicated in a variety of human infections;
      however, many clinical microbiology laboratories in Nigeria do not identify
      staphylococci (in particular coagulase negative staphylococci - CNS) to the
      species level. Moreover, data from multi-centre assessment on antibiotic
      resistance and epidemiology of the staphylococci are not available in Nigeria.
      This study investigated 91 non-duplicate staphylococcal isolates obtained from
      the microbiology laboratories of eight hospitals in Nigeria during the period
      January to April 2010. METHODS: Identification and antibiotic susceptibility
      testing was performed using the VITEK 2 system, detection of resistance genes by
      PCR, and molecular characterization was determined by SCCmec typing, spa and
      multilocus sequence typing (MLST). RESULTS: All the isolates were susceptible to
      mupirocin, tigecycline, vancomycin and linezolid, but 72.5% of CNS and 82.3% of
      Staphylococcus aureus were resistant to cotrimoxazole, while multiresistance was
      observed in 37 of the 40 CNS isolates. Untypeable SCCmec types (ccrC/Class A mec
      and ccr-negative/Class C2 mec gene complex) in two methicillin-resistant S.
      aureus (MRSA) were identified. Additionally, ccr-negative/Class A mec and ccr
      type 4/Class C2 mec gene complex was detected in one isolate each of S. sciuri
      and S. haemolyticus, respectively. The S. aureus isolates were classified into 21
      spa types including two new types (t8987, t9008) among the methicillin
      susceptible S. aureus (MSSA) isolates. Two (CC8-SCCmecnon-typeable and CC88
      SCCmec IV) and four (CC8-SCCmec III/IV/V; CC30-SCCmec II/III; CC88-SCCmec IV; and
      ST152-SCCmecnon-typeable) MRSA clones were identified in Maiduguri (North-East
      Nigeria) and South-West Nigeria, respectively. The proportion of Panton-Valentine
      leukocidin (PVL)-positive MSSA was high (44.4%) and 56.3% of these strains were
      associated with sequence type (ST) 152. CONCLUSIONS: The identification of
      multiresistant mecA positive S. haemolyticus and S. sciuri from clinical samples
      indicates that characterization of CNS is important in providing information on
      their diversity and importance in Nigeria. There is the need to develop new
      SCCmec classification methods for non-typeable methicillin-resistant
      staphylococci, and to curtail the spread and establishment of the S. aureus ST152
      clone in Nigeria. The study presents the first report of a PVL-positive ST152
      SCCmecnontypeable MRSA and SCCmec typing of methicillin-resistant CNS in Nigeria.

PMID- 23121722
TI  - N-Phenyl-4-hydroxy-2-quinolone-3-carboxamides as selective inhibitors of mutant
      H1047R phosphoinositide-3-kinase (PI3Kalpha).
AB  - This work describes our efforts to optimize the lead PI3Kalpha inhibitor N-benzyl
      4-hydroxy-2-quinolone-3-carboxamide using structure-based design and molecular
      docking. We identified a series of N-phenyl 4-hydroxy-2-quinolone-3-carboxamides
      as selective inhibitors of mutant H1047R versus wild-type PI3Kalpha and we also
      showed that the cell growth inhibition by these compounds likely occurs by
      inhibiting the formation of pAKT and induction of apoptosis.

PMID- 23121724
TI  - Association of statin use with peripheral neuropathy in the U.S. population 40
      years of age or older.
AB  - BACKGROUND: Peripheral neuropathy is a serious complication of diabetes and
      several conditions that may lead to the loss of lower extremity function and even
      amputations. Since the introduction of statins, their use has increased markedly.
      Recent reports suggest a role for statins in the development of peripheral
      neuropathy. The aims of the present study were to assess the association between
      statin use and peripheral neuropathy, and to determine whether this association
      varied by diabetes status. METHODS: Data from the lower extremity examination
      supplement of the 1999-2004 National Health and Nutrition Examination Survey were
      used. RESULTS: The overall prevalence of statin use was 15% and the prevalence of
      peripheral neuropathy was 14.9%. The prevalence of peripheral neuropathy was
      significantly higher among those who used statins compared with those who did not
      (23.5% vs 13.5%, respectively; P < 0.01). Multivariate logistic regression
      revealed that statin use (adjusted odds ratio 1.3; 95% confidence interval 1.1
      1.6; Wald P = 0.04) was significantly associated with peripheral neuropathy,
      controlling for diabetes status, age, gender, race, height, weight, blood lead
      levels, poverty, glycohemoglobin, use of vitamin B12 , alcohol abuse,
      hypertension, and non-high-density lipoprotein-cholesterol. Diabetes status, age,
      gender, height, weight, blood lead levels, poverty, and glycohemoglobin were also
      significantly associated with peripheral neuropathy. We found no effect
      modification between statin use and diabetes status, race, gender, age, vitamin
      B12 , blood lead levels, or alcohol abuse. CONCLUSIONS: In the present cross
      sectional study, we found a modest association between peripheral neuropathy and
      statin use. Prospective studies are required to determine the causal direction.

PMID- 23121723
TI  - Focus on increasing treatment self-efficacy to improve human immunodeficiency
      virus treatment adherence.
AB  - PURPOSE: Human immunodeficiency virus (HIV) treatment self-efficacy is the
      confidence held by an individual in her or his ability to follow treatment
      recommendations, including specific HIV care such as initiating and adhering to
      antiretroviral therapy (ART). The purpose of this study was to explore the
      potential mediating role of treatment adherence self-efficacy in the
      relationships between Social Cognitive Theory constructs and self- reported ART
      adherence. DESIGN: Cross-sectional and descriptive. The study was conducted
      between 2009 and 2011 and included 1,414 participants who lived in the United
      States or Puerto Rico and were taking antiretroviral medications. METHODS: Social
      cognitive constructs were tested specifically: behaviors (three adherence
      measures each consisting of one item about adherence at 3-day and 30-day along
      with the adherence rating scale), cognitive or personal factors (the Center for
      Epidemiology Studies Depression Scale to assess for depressive symptoms, the 12
      Item Short Form Health Survey (SF-12) to assess physical functioning, one item
      about physical condition, one item about comorbidity), environmental influences
      (the Social Capital Scale, one item about social support), and treatment self
      efficacy (HIV Adherence Self-Efficacy Scale). Analysis included descriptive
      statistics and regression. RESULTS: The average participant was 47 years old,
      male, and a racial or ethnic minority, had an education of high school or less,
      had barely adequate or totally inadequate income, did not work, had health
      insurance, and was living with HIV/acquired immunodeficiency syndrome for 15
      years. The model provided support for adherence self-efficacy as a robust
      predictor of ART adherence behavior, serving a partial mediating role between
      environmental influences and cognitive or personal factors. CONCLUSIONS: Although
      other factors such as depressive symptoms and lack of social capital impact
      adherence to ART, nurses can focus on increasing treatment self-efficacy through
      diverse interactional strategies using principles of adult learning and
      strategies to improve health literacy. CLINICAL RELEVANCE: Adherence to ART
      reduces the viral load thereby decreasing morbidity and mortality and risk of
      transmission to uninfected persons. Nurses need to use a variety of strategies to
      increase treatment self-efficacy.

PMID- 23121725
TI  - Effect of supplementation of different growth factors in embryo culture medium
      with a small number of bovine embryos on in vitro embryo development and quality.
AB  - When embryos are cultured individually or in small groups, blastocyst yield
      efficiency and quality are usually reduced. The aim of this work was to
      investigate the effect of supplementation of the embryo culture medium (CM) with
      several growth factors (GFs) on embryo development and apoptosis rate when a
      reduced number of embryos were in vitro cultured. Two experimental studies (ES)
      were carried out. In ES 1, five treatments were tested to study the effect of GF
      on embryo development: Control (~30 to 50 embryos cultured in 500 MUl of CM);
      Control 5 (Five embryos cultured in 50 MUl microdrops of CM), without addition of
      GF in either of the two control groups; epidermal GF (EGF); IGF-I; and
      transforming GF-alpha (TGF-alpha) (Five embryos were cultured in 50 MUl
      microdrops of CM with 10 ng/ml EGF, 10 ng/ml IGF-I or 10 ng/ml TGF-alpha,
      respectively). In ES 2, following the results obtained in ES 1, four different
      treatments were tested to study their effect on embryo development and quality
      (number of cells per blastocyst and apoptotic rate): Control; Control 5; EGF, all
      three similar to ES 1; EGF + IGF-I group (five embryos cultured in 50 MUl
      microdrops of CM with 10 ng/ml EGF and 10 ng/ml IGF-I). In both ESs, it was
      observed that a higher proportion of embryos cultured in larger groups achieved
      blastocyst stage than embryos cultured in reduced groups (22.6% v. 14.0%, 12.6%
      and 5.3% for Control v. Control 5, IGF-I, TGF-alpha groups in ES 1, and 24.9% v.
      17.1% and 19.0% for Control v. Control 5 and EGF in ES 2, respectively; P <
      0.05), with the exception of embryos cultured in medium supplemented with EGF
      (18.5%) or with EGF + IGF-I (23.5%), in ES 1 and ES 2, respectively. With regard
      to blastocyst quality, embryos cultured in reduced groups and supplemented with
      EGF, alone or combined with IGF-I, presented lower apoptosis rates than embryos
      cultured in reduced groups without GF supplementation (11.6% and 10.5% v. 21.9%
      for EGF, EGF + IGF-I and Control 5 groups, respectively; P < 0.05). The
      experimental group did not affect the total number of cells per blastocyst. In
      conclusion, this study showed that supplementation of the CM with EGF and IGF
      could partially avoid the deleterious effect of in vitro culture of small groups
      of bovine embryos, increasing blastocyst rates and decreasing apoptosis rates of
      these blastocysts.

PMID- 23121726
TI  - Response to "Does STN-DBS Improve Balance in Parkinson Disease?".

PMID- 23121727
TI  - Dopamine D2 receptor SPECT in corticobasal syndrome and autopsy-confirmed
      corticobasal degeneration.
AB  - BACKGROUND: Corticobasal degeneration (CBD) is a rare neurodegenerative disorder
      characterized by tau-positive neuronal and glial lesions in the cortex and
      striatum with neuronal loss in cortical regions and in the substantia nigra.
      Striatal dopamine D2 receptor binding in autopsy-confirmed CBD has not been
      studied before. METHODS: We performed D2 receptor single photon emission
      computerized tomography using (123)I-IBZM in nine patients with a clinically
      diagnosed corticobasal syndrome (CBS) and on ten healthy controls. Two of the
      patients subsequently came to autopsy and were diagnosed with CBD. RESULTS:
      Overall striatal D2 receptor binding was preserved in 8/9 patients, but more
      asymmetric than in controls. Overall striatal binding in pathologically confirmed
      CBD was reduced in one case and normal in the other, and was lower contralateral
      to the clinically more affected side in both. CONCLUSION: This first study on D2
      receptor imaging in autopsy-confirmed CBD demonstrates that loss of postsynaptic
      striatal neurons in CBD is a variable finding. Given the heterogeneity of our
      findings in pathology-confirmed cases, D2 receptor imaging seems to be of little
      practical value in the diagnostic workup of patients with CBS.

PMID- 23121728
TI  - Does rate of progression run in essential tremor families? Slower vs. faster
      progressors.
AB  - BACKGROUND: Essential tremor (ET) is a progressive disorder, worsening gradually
      with time in most patients. Yet there are few data on the factors that influence
      rate of progression. ET is a highly familial disorder, and physicians often care
      for patients who have other affected family members. Do ET families differ from
      one another with respect to rate of progression? Are some families slower
      progressors and other families faster progressors? We are unaware of published
      data. METHODS: ET probands and relatives were enrolled in a cross-sectional
      genetic study at Columbia University. Rate of progression was calculated as total
      tremor score / log disease duration. RESULTS: There were 100 enrollees (28
      probands, 72 relatives). Data from 78 enrollees (23 probands, 55 relatives) were
      selected for final analysis. The mean familial rate of progression ranged from as
      little as 8.4 to as much as 34.3, a > 4-fold difference. In an analysis of
      variance, we found significant evidence of heterogeneity in the log rate of
      progression across families (p < 0.001), with more than one-half (i.e., 55.4%) of
      the total variance in the log rate of progression explained by the family
      grouping. CONCLUSIONS: Familial factors seem to affect rate of tremor progression
      in ET. There was a 4-fold difference across families in observed mean rate of
      progression; thus, some families seemed to be more rapid progressors than others.
      We hope these data may be used by clinicians to provide basic prognostic and
      family guidance information to their patients and families with ET.

PMID- 23121729
TI  - Novel SPG11 mutations in Chinese families with hereditary spastic paraplegia with
      thin corpus callosum.
AB  - BACKGROUND: Hereditary spastic paraplegia is a clinically and genetically
      heterogeneous neurodegenerative disorder characterized by progressive spasticity
      of the lower limbs. Mutations in SPG11 gene have been recently identified as a
      major cause of hereditary spastic paraplegia with thin corpus callosum. METHODS:
      Two unrelated Chinese families were examined by clinical evaluation, mutation
      analysis of SPG11, detailed neuropsychological assessment and diffusion tensor
      imaging. RESULTS: Both patients presented with spastic paraparesis and learning
      disability. Two novel and one known mutations in SPG11 were detected through
      genetic analysis. Cognitive impairment was found with severe deficits in domains
      such as executive functions and memory. Magnetic resonance imaging showed thin
      corpus callosum while diffusion tensor imaging revealed increased mean diffusion
      and decreased fractional anisotropy in the corpus callosum and subcortical white
      matter in frontal, temporal lobe compared with the healthy controls. CONCLUSIONS:
      This study widens the spectrum of mutations in SPG11. The application of detailed
      neuropsychological tests and diffusion tensor imaging could detect cerebral
      subtle involvement even in early stage of the disease.

PMID- 23121730
TI  - Quantitative tools for addressing hospital readmissions.
AB  - BACKGROUND: Increased interest in health care cost containment is focusing
      attention on reduction of hospital readmissions. Major payors have already
      developed financial penalties for providers that generate excess readmissions.
      This subject has benefitted from the development of resources such as the
      Potentially Preventable Readmissions software. This process has encouraged
      hospitals to renew efforts to improve these outcomes. The aim of this study was
      to describe quantitative tools such as definitions, risk estimation, and tracking
      of patients for reducing hospital readmissions. FINDINGS: This study employed the
      Potentially Preventable Readmissions software to develop quantitative tools for
      addressing hospital readmissions. These tools included two definitions of
      readmissions that support identification and management of patients. They also
      included analytical approaches for estimation of the risk of readmission for
      individual patients by age, discharge status of the initial admission, and
      severity of illness. They also included patient specific spreadsheets for
      tracking of target populations and for evaluation of the impact of interventions.
      CONCLUSIONS: The study demonstrated that quantitative tools including the
      development of definitions of readmissions, estimation of the risk of
      readmission, and patient specific spreadsheets could contribute to the
      improvement of patient outcomes in hospitals.

PMID- 23121731
TI  - A comparison of patient characteristics, prognosis, treatment modalities, and
      survival according to age group in gastric cancer patients.
AB  - BACKGROUND: The aim of this study was to investigate age-specific incidence rates
      and to compare disease stage, treatment, and survival according to age group in
      patients with gastric adenocarcinoma. METHODS: Gastric cancer patients treated at
      our hospital between 1999 and 2010 were retrospectively evaluated. We divided the
      cases into two subgroups: group 1 consisted of patients older than 70 years at
      the time of treatment, and group 2 included patients aged 70 years or younger. In
      all, 151 patients over 70 years of age and 715 patients age 70 years or younger
      were analyzed. Categorical and continuous variables were summarized using
      descriptive statistics and compared using statistical software. Overall survival
      rates were estimated via the Kaplan-Meier method. RESULTS: Median age at
      diagnosis was 58 years (range: 22 to 90 years). Between 1999 and 2002 the annual
      median age for patients aged older than70 years was 9.8%, which increased to 20%
      between 2007 and 2010. The one-year survival rate for patients with metastatic
      disease (stage IV) was 10.9% (95% CI: 8.9% to 12.9%) and 27.8% (95% CI: 17.3% to
      38.2%) in groups 1 and 2, respectively (P = 0.015). The five-year survival rate
      for patients with non-metastatic disease (in whom curative surgery was performed)
      was 15.5% (95% CI = 12% to 19%) and 26.9% (95% CI = 25.9% to 27.9%) in groups 1
      and 2, respectively (P = 0.03). There were no significant differences in gender,
      tumor localization in the stomach, tumor histology, perineural invasion (PNI),
      lymphovascular invasion (LVI), tumor stage, or type of surgery between the two
      groups. However, fewer of the patients in group 1 underwent adjuvant treatment (P
      = 0.02) and palliative chemotherapy (P = 0.007) than group 2 patients that were
      non-metastatic and metastatic at presentation, respectively. CONCLUSIONS: Groups
      1 and 2 were similar in terms of histopathological features and surgical
      modality; however, the survival rate was lower in group 1 than in group 2. The
      incidence of gastric cancer was higher in the patients older than 70 years of
      age. Additional randomized studies are needed to further assess the safety and
      clinical benefit of chemotherapy in gastric cancer patients older than70 years of
      age.

PMID- 23121732
TI  - Grafting of functional motifs onto protein scaffolds identified by PDB screening-
      an efficient route to design optimizable protein binders.
AB  - Artificial miniproteins that are able to target catalytic sites of matrix
      metalloproteinases (MMPs) were designed using a functional motif-grafting
      approach. The motif corresponded to the four N-terminal residues of TIMP-2, a
      broad-spectrum protein inhibitor of MMPs. Scaffolds that are able to reproduce
      the functional topology of this motif were obtained by exhaustive screening of
      the Protein Data Bank (PDB) using STAMPS software (search for three-dimensional
      atom motifs in protein structures). Ten artificial protein binders were produced.
      The designed proteins bind catalytic sites of MMPs with affinities ranging from
      450 nm to 450 MUm prior to optimization. The crystal structure of one artificial
      binder in complex with the catalytic domain of MMP-12 showed that the inter
      molecular interactions established by the functional motif in the artificial
      binder corresponded to those found in the MMP-14-TIMP-2 complex, albeit with some
      differences in geometry. Molecular dynamics simulations of the ten binders in
      complex with MMP-14 suggested that these scaffolds may allow partial reproduction
      of native inter-molecular interactions, but differences in geometry and stability
      may contribute to the lower affinity of the artificial protein binders compared
      to the natural protein binder. Nevertheless, these results show that the in
      silico design method used provides sets of protein binders that target a specific
      binding site with a good rate of success. This approach may constitute the first
      step of an efficient hybrid computational/experimental approach to protein binder
      design.

PMID- 23121733
TI  - Prevalence of diminished kidney function in a representative sample of middle and
      older age adults in the Irish population.
AB  - BACKGROUND: The prevalence of chronic kidney disease (CKD) using available
      estimating equations with the Republic of Ireland is unknown. METHODS: A randomly
      selected population based cross-sectional study of 1,098 adults aged 45 years and
      older was conducted using data from the 2007 Survey of Lifestyle, Attitudes and
      Nutrition (SLAN). Estimated Glomerular Filtration Rate (eGFR) was calculated from
      a single IDMS aligned serum creatinine using the CKD-EPI and the MDRD equations,
      and albumin to creatinine ratio was based on a single random urine sample.
      RESULTS: The sample clinical characteristics and demography was similar to middle
      and older age adults in the general Irish population, though with an
      underrepresentation of subjects >75 years and of males. All results are based on
      subjects with available blood and urine samples. Applying weighting to obtain
      survey based population estimates, using Irish population census data, the
      estimated weighted prevalence of CKD-EPI eGFR<60 mL/min/1.73m2 was 11.6%, (95%
      confidence interval; 9.0, 14.2%), 12.0% ( 9.0, 14.2%) of men and 11.2% (7.3,
      15.2%) of women. Unweighted prevalence estimates were similar at 11.8% (9.9,
      13.8%). Albuminuria increased with lower CKD-EPI eGFR category. 10.1% of all
      subjects had albuminuria and an eGFR>=60 mL/min/1.73 m2 giving an overall
      weighted estimated prevalence of National Kidney Foundation (NKF) defined CKD
      21.3% (18.0, 24.6%), with the unadjusted estimate of 21.9% (19.5, 24.4%). MDRD
      related estimates for eGFR <60 mL/min/1.73 m2, and NFK defined CKD were higher
      than CKD-EPI and differences were greater in younger and female subjects.
      CONCLUSIONS: CKD is highly prevalent in middle and older aged adults within the
      Republic of Ireland. In this population, there is poor agreement between CKD-EPI
      and MDRD equations especially at higher GFRs. CKD is associated with lower
      educational status and poor self rated health.

PMID- 23121734
TI  - Gender differences regarding informal caregivers of older people.
AB  - PURPOSE: The aim of this study was to examine differences related to gender among
      informal caregivers serving older disabled individuals. DESIGN AND METHODS: A
      secondary analysis of the most recent national cross-sectional survey, which was
      conducted in Spain on informal caregivers who served older individuals (65 years
      of age or older), was conducted in 2011 (N= 1,272, probability sample). The
      relationships between gender and intensity of care (amount and type of care
      provided), duration of caregiving, subjective burden, and satisfaction with
      caregiving were analyzed by bivariate and multivariate procedures. FINDINGS: No
      statistically significant gender differences were found with regard to the
      intensity of care, duration of caregiving, or satisfaction; however, subjective
      burden was found to differ between men and women, and this difference was
      statistically significant (odds ratio = 1.98; p= .012). CONCLUSIONS: Because this
      study was conducted in Spain, a country with strong patriarchal norms with regard
      to caregiving and familism, whereas gender differences in intensity of care have
      been reported in countries with low familism, we conclude that cultural diversity
      can influence the relationship between gender and intensity of care. On the other
      hand, our study increases the evidence in support of there being gender-based
      differences in subjective burden among family caregivers serving older people in
      Western industrial countries. Finally, the results of our study support the
      hypothesis that sources of satisfaction are more strongly related to the
      caregiver's personal context and characteristics than to his or her gender.
      CLINICAL RELEVANCE: These findings support the following recommendations
      regarding nursing interventions: (a) nurses should take into account specific
      cultural patterns in caregiving to improve their understanding concerning the
      relationships between gender and intensity of care, and (b) gender should be
      taken into account in interventions that are tailored toward addressing
      subjective burden.

PMID- 23121735
TI  - Back to basics: an evaluation of NaOH and alternative rapid DNA extraction
      protocols for DNA barcoding, genotyping, and disease diagnostics from fungal and
      oomycete samples.
AB  - The ubiquity, high diversity and often-cryptic manifestations of fungi and
      oomycetes frequently necessitate molecular tools for detecting and identifying
      them in the environment. In applications including DNA barcoding, pathogen
      detection from plant samples, and genotyping for population genetics and
      epidemiology, rapid and dependable DNA extraction methods scalable from one to
      hundreds of samples are desirable. We evaluated several rapid extraction methods
      (NaOH, Rapid one-step extraction (ROSE), Chelex 100, proteinase K) for their
      ability to obtain DNA of quantity and quality suitable for the following
      applications: PCR amplification of the multicopy barcoding locus ITS1/5.8S/ITS2
      from various fungal cultures and sporocarps; single-copy microsatellite
      amplification from cultures of the phytopathogenic oomycete Phytophthora ramorum;
      probe-based P. ramorum detection from leaves. Several methods were effective for
      most of the applications, with NaOH extraction favored in terms of success rate,
      cost, speed and simplicity. Frozen dilutions of ROSE and NaOH extracts maintained
      PCR viability for over 32 months. DNA from rapid extractions performed poorly
      compared to CTAB/phenol-chloroform extracts for TaqMan diagnostics from tanoak
      leaves, suggesting that incomplete removal of PCR inhibitors is an issue for
      sensitive diagnostic procedures, especially from plants with recalcitrant leaf
      chemistry. NaOH extracts exhibited lower yield and size than CTAB/phenol
      chloroform extracts; however, NaOH extraction facilitated obtaining clean
      sequence data from sporocarps contaminated by other fungi, perhaps due to
      dilution resulting from low DNA yield. We conclude that conventional extractions
      are often unnecessary for routine DNA sequencing or genotyping of fungi and
      oomycetes, and recommend simpler strategies where source materials and intended
      applications warrant such use.

PMID- 23121737
TI  - Chaos in Western Medicine: how issues of social-professional status are
      undermining our health.
AB  - From the period immediately following the second world war, western (orthodox)
      medicine - both as a philosophy of medicine and as a professional guild of
      medical professionals actively practicing medicine - has made progress in leaps
      and bounds, especially considering the advances in technology and associated
      enterprises. Over the last thirty years, however, the practice of orthodox
      medicine has taken a turn for the worst despite progressive philosophies and
      tenets of basic practice as offered by the professional bodies that regulate how
      medicine is operated and implemented. Current healthcare environments are in a
      chaotic state of affairs, most notably due to issues involving affordability of
      medical professionals. It is argued that the social-professional status of
      medical doctors allow exorbitant and unreachable demands on governments for
      increased salaries. The title-based supremacy of doctors within the occupations
      domain is not supported by what they are offering society at large, and it
      compromises the ability of medical institutions and governments to provide better
      and more affordable healthcare. From a sociological point of view, this paper
      examines the social-religious history of such social class-based occupational
      power and dominance, and paves the way toward an overhaul of current medical
      education frameworks that proactively will ensure greater occupational equity in
      healthcare settings, across all healthcare disciplines tasked with patient care
      and improvement of healthcare services. In essence, doctoral titles should only
      be awarded after successful completion of postgraduate doctoral studies, and a
      new breed of medical professionals must emerge, able to contribute more
      meaningfully to the advancement of medicine as a profession, as well as toward
      increased standards of healthcare and improved health services delivery.

PMID- 23121736
TI  - Gamma-H2AX foci in cells exposed to a mixed beam of X-rays and alpha particles.
AB  - BACKGROUND: Little is known about the cellular effects of exposure to mixed
      beams of high and low linear energy transfer radiation. So far, the effects of
      combined exposures have mainly been assessed with clonogenic survival or
      cytogenetic methods, and the results are contradictory. The gamma-H2AX assay has
      up to now not been applied in this context, and it is a promising tool for
      investigating the early cellular response to mixed beam irradiation. PURPOSE: To
      determine the dose response and repair kinetics of gamma-H2AX ionizing radiation
      induced foci in VH10 human fibroblasts exposed to mixed beams of 241Am alpha
      particles and X-rays. RESULTS: VH10 human fibroblasts were irradiated with each
      radiation type individually or both in combination at 37 degrees C. Foci were
      scored for repair kinetics 0.5, 1, 3 and 24 h after irradiation (one dose per
      irradiation type), and for dose response at the 1 h time point. The dose response
      effect of mixed beam was additive, and the relative biological effectiveness for
      alpha particles (as compared to X-rays) was of 0.76 +/- 0.52 for the total number
      of foci, and 2.54 +/- 1.11 for large foci. The repair kinetics for total number
      of foci in cells exposed to mixed beam irradiation was intermediate to that of
      cells exposed to alpha particles and X-rays. However, for mixed beam-irradiated
      cells the frequency and area of large foci were initially lower than predicted
      and increased during the first 3 hours of repair (while the predicted number and
      area did not). CONCLUSIONS: The repair kinetics of large foci after mixed beam
      exposure was significantly different from predicted based on the effect of the
      single dose components. The formation of large foci was delayed and they did not
      reach their maximum area until 1 h after irradiation. We hypothesize that the
      presence of low X-ray-induced damage engages the DNA repair machinery leading to
      a delayed DNA damage response to the more complex DNA damage induced by alpha
      particles.

PMID- 23121738
TI  - Cost burden of post stroke condition in Nigeria: a pilot study.
AB  - AIM: Estimation of cost burden of a disease condition is a very important part of
      health care policy making worldwide. Till now, such documents are lacking
      especially on non-communicable diseases in the health policy making process in
      Nigeria. This article therefore attempts to report the results of a prospective
      cross-sectional study on the cost burden of a cerebrovascular accident condition
      (stroke) in Nigeria. It estimates the direct health care cost for a minimum
      period of 12 weeks and maximum of 36 weeks for post stroke hemiplegia. STUDY
      DESIGN/SETTING: It was a collaborative cross-sectional study amongst centers
      situated in urban and sub-urban environments in Southern Nigeria. It involved a
      hospital of an Oil and Gas Company in Port Harcourt, Nigeria, two Government
      tertiary hospitals in Port Harcourt and Benin-City, all in South-South Nigeria,
      the industrial hub of the country. A Private Specialist hospital in Lagos, South
      West Nigeria, the corporate hub of the country was also included. METHOD:
      Patients diagnosed and admitted for management for cerebrovascular accident
      (stroke) in the above named health facilities formed the subjects of this study.
      Medical records (case files) of two hundred and forty (240) stroke patients
      managed within the last six years (2005- 2011) were randomly selected from the
      medical record departments of the study centers. Files of the patients who were
      admitted during acute care period (without discharge against medical advice) and
      were followed on out-patient basis without default within the study period were
      purposively utilized. The files were then assessed for the various investigations
      and treatment interventions of acute and long term care and the costs thereof.
      Ethical approval to access patients' case files was sought and granted by the
      Research Ethics Committee of the different study centers. RESULTS: The results
      revealed that it requires an average of N95,100: 00 ($600 ) and N767,900: 00
      ($4860)in a government and a private hospital, respectively to access care within
      the first 36 weeks of post stroke affectation in Nigeria. CONCLUSION: The outcome
      of this study suggests that managing stroke constitutes a huge direct cost burden
      unaffordable by an average Nigerian stroke sufferer. The implication is that lack
      of means for rehabilitative care may result in disability adjusted life years
      which further compounds burdens in terms of indirect cost on the sufferers' and
      care givers' productivity. It is therefore recommended that awareness of this
      disorder is created by policy makers and implementers where it does not exist and
      increased where it does with health promotion and preventive measures.

PMID- 23121739
TI  - Predictors of access to healthcare: what matters to rural Appalachians?
AB  - OBJECTIVE: Lack of access to healthcare is frequently cited as a primary reason
      for health disparities globally, especially in poor, rural areas such as
      Appalachia in the U.S. This study examined predictors of perceived access to
      healthcare among residents in a poor, medically underserved, rural Appalachian
      community. METHODS: The study was guided by the revised behavioral model of
      healthcare services utilization. Self-reported survey data were obtained from a
      convenience sample of 921 residents in rural Tennessee. RESULTS: The majority of
      respondents in this study did not perceive access to healthcare to be a problem
      in their community. Financial factors, health status, and associated social
      factors negatively affected only a small number respondents' perceptions of
      access to healthcare. CONCLUSIONS: Despite the presence of multiple factors
      previously shown to affect access to healthcare, the majority of respondents in
      this study did not perceive access to healthcare to be a problem in their
      community. Results of this study suggest that to understand an individual's
      passage through the healthcare system, the contextual aspects of healthcare
      utilization, should be added to coverage, services, timeliness, and workforce as
      a fifth component of access to healthcare. Assessing perceived need and
      associated cultural factors that affect individuals' concepts of health and
      wellness represent important areas for future exploration to explain observed
      health disparities. Additionally, findings showed that having sufficient quality
      and quantity of healthcare professionals and services in a community or region
      may be necessary, but not sufficient to explain health disparities and the
      underlying reasons why individuals choose or choose not to seek health services.

PMID- 23121740
TI  - Therapy recommendation "act as usual" in patients with whiplash injuries QTF I
      degrees .
AB  - Up to now no therapy study has used the classification system of the Quebec Task
      Force (QTF) to differentiate between patients with (QTF II degrees ) and without
      functional disorders (QTF I degrees ). This differentiation seems meaningful, as
      this difference may be relevant for the correct treatment planning. In this
      context the effect of the therapy recommendation "act as usual" has been
      evaluated in a homogeneous patient collective with whiplash injuries QTF I
      degrees . 470 patients with acute whiplash injuries had been catched in this
      study and classified according to the QTF. 359 patients (76.4%) with QTF I
      degrees  injuries could be identified. Out of that 162 patients were enrolled to
      the study and received the therapy recommendation "act as usual" and the adapted
      pain treatment with non-steroidal anti-inflammatory drugs (NSAID). After six
      months the outcome was evaluated by phone. After injury the median pain score
      assessed by a visual analogue scale (VAS) was 5.4 (min = 3.3; max = 8.5). After
      six months 5 of the 162 patients complained intermittent pain symptoms (VAS
      values < 2). This is consistent with a chronification rate of 3.1%. After injury,
      the median pain disability index (PDI) was 3.9 (min = 1.9; max = 7.7). After six
      months 3 of the 162 patients stated persisting disability during sporting and
      physical activities (VAS values < 1). The therapy recommendation "act as usual"
      in combination with an adapted pain treatment is sufficient. Usually patients
      with whiplash injuries QTF I degrees  do not need physical therapy. An escalation
      of therapy measures should be reserved to patients with complicated healing
      processes.

PMID- 23121741
TI  - Health questions posed by Amerindians in Guyana's deep interior.
AB  - BACKGROUND: The forest-dwelling Amerindian peoples of Guyana are among that
      nation's most impoverished, vulnerable and least served. Health promotion
      messaging has been informed in large part by nation-level health indicators that
      may not be well targeted to this group. Our study sought to identify local health
      education needs, and to identify factors preventing proper uptake of health
      messaging. METHODS: As part of medical missions to the interior, we asked
      patients waiting for care to anonymously submit their health questions in
      writing. Conventional content analysis was employed to identify prevalent themes
      in their responses. FINDINGS: Sexual health (63.6%) and nutrition (17.4%) were
      the most popular themes asked about. Within the former, the science of sexual
      maturation and reproduction (31.4%) and HIV/AIDS (28.8%) were the most common sub
      themes, with the pathophysiology and etiology of HIV/AIDS being the most common
      sub-theme within the latter. INTERPRETATION: Within Guyana's Amerindian
      community, there exists a prevalent curiosity about the basic science of both
      sexual reproduction and the transmission of sexual disease.

PMID- 23121742
TI  - Clinical complaints amongst patients in a Guyanese prison.
AB  - BACKGROUND: Incarcerated populations are at particular risk for developing
      specific health conditions.  Prior studies of prisons in developing countries
      have focused on the threat of communicable diseases, though anecdotal evidence
      suggests that chronic conditions are of particular concern. This study
      constitutes the first published investigation of health complaints offered by
      residents of a prison in the South American nation of Guyana. METHOD: In 2010, a
      medical team sent by the Toronto non-governmental organization Ve'ahavta visited
      the Mazaruni prison in the interior of Guyana. Data on patient encounters was
      collected as part of the triage activity. RESULTS: Care was given to 108
      patients, staff and family members. Contrary to literature expectations, 50% of
      complaints concerned musculoskeletal issues, while only 11% were genitor
      reproductive. Upon examination, 30.6% of patients were experiencing
      musculoskeletal problems, most commonly back pain. CONCLUSION: Future medical
      interventions to this and comparable low- and middle-income country prisons
      should more vigorously consider physiotherapeutic interventions, in addition to
      the expected addressing of infectious diseases.

PMID- 23121743
TI  - Hazards analysis, within departments and occupations, for hepatitis B virus among
      health care workers in Public Teaching Hospitals in Khartoum State; Sudan.
AB  - BACKGROUND: Infection with hepatitis B virus (HBV) can lead to a range of
      clinical illnesses. OBJECTIVES: To examine hazards of hepatitis B virus
      associated with clinical departments and occupations; among health care workers
      in Public Teaching Hospitals in Khartoum State, Sudan. METHODS: The study was a
      cross sectional, facility-based study. It was conducted on stratified two-stage
      cluster random sample of 843 subjects of whom 324 were at high-hazard, 445 at
      moderate hazard, and 74 at low hazard; depending on degree of exposure to blood
      and body fluids of patients. To assess hazards of HBV among departments and
      occupations of HCWs, non-parametric Methods of Chi-square test, was used.
      RESULTS: For Anti-HBc vulnerable departments was Renal Dialysis (100%); while for
      occupations was midwives (73.3%). For carrier rate (+ve HBsAg), highest rate
      found in department of Management (6.8%); while for occupations was Midwives
      (6.7%). Regarding immunity (+ve Anti-HBs), the highest percentage found in the
      department of Dentistry (25.9%); while for occupations was associated with
      Doctors (14.8%). For a profile of high infectivity (+ve HBeAg), the most
      vulnerable department in terms of HBV hazards was the Surgery (1.4%); while for
      occupations was nurses (0.9%). CONCLUSION: There was a significant association
      for infection rate of HBV with occupation and type of department. The most
      hazardous departments, was Surgery with a profile of high infectivity rate,
      followed by other departments (medicine, pediatrics, psychiatry & ophthalmology).
      As for occupations, the most hazardous group was nurses group with a profile of
      high infectivity rate.

PMID- 23121744
TI  - Does experience of failure decrease executive, regulatory abilities and increase
      aggression?
AB  - Recent advances in the study of affective-cognitive regulation of aggressive
      behavior suggest positive correlations between poor executive capacities (ECF)
      and dispositional negative reactivity (Posner & Rothbart, 2000). If the global
      assumption is correct what are the likely implications of predicted relation? The
      central issue in present research was to verify this assumption and examine how
      situational characteristics could alter executive performance in persons with
      Dysexecutive Syndrome (DES, Baddeley, 1998) and healthy adults (students, health
      workers) to explore some of the consequences of those modifications for
      aggressive tendencies. Precisely, we expected the positive correlations between
      poor executive performances and high aggressive tendencies at dispositional as
      well situational levels, except for health workers, given their professional
      duties. In order to assess cognitive capacities and dispositional as well as
      situational aggressive tendencies, during two studies (First study: N=60
      students; Second study: N= 60 students, N= 24 patient with Dysexecutive Syndrome,
      ; N= 45 health care workers) right-handed French-speakers participants completed
      twice, during an initial phase of the study and one week after, a series of
      standard executive functions neuropsychological tests and aggression
      questionnaires. During second phase, participants executed a task introducing the
      experimental feedbacks (success, neutral, failure) before completion of
      neuropsychological tests and questionnaires. The results provided evidence of a
      dispositional relationship between poor executive functioning and aggressive
      tendencies, and extended it to situational level. For all participants, it showed
      that increases in impulsiveness (negative emotionality and aggressive choices)
      due to a negative feedback were concomitant with an inability to focus
      individuals' attention on ongoing tasks.

PMID- 23121745
TI  - Assisted or hastened death: the healthcare practitioner's dilemma.
AB  - Assisting or hastening death is a dilemma with many ethical as well as practical
      issues facing healthcare practitioners in many countries worldwide now. Various
      arguments for and against assisted dying have been made over time but the call
      from the public for legalisation of euthanasia or assisted suicide has never been
      stronger. While many studies have documented the reluctance of medical and other
      health professionals to be involved in the practice of assisted dying or
      euthanasia, there is still much open debate in the public domain. Those who have
      the most experience of palliative care are strongest in their opposition to
      assisted death or euthanasia. This paper explores salient practical and ethical
      considerations for healthcare practitioners associated with assisted death, with
      a focus on examining the concepts of autonomy for patients and healthcare
      practitioners. The role of the healthcare practitioner has clearly and
      undoubtedly changed over time with advances in healthcare practices but the duty
      of care has not changed. The dilemmas for healthcare practitioners thus who have
      competent patients requesting hastened death extends far beyond acting within a
      country's laws as they go to the very heart of the relationship between the
      practitioner and patient.

PMID- 23121746
TI  - Health disparities experienced by people with disabilities in the United States:
      a Behavioral Risk Factor Surveillance System study.
AB  - The Americans with Disabilities Act became law in 1990; since then research has
      shown that people with disabilities continue to experience barriers to health
      care. The purpose of this study was to compare utilization of preventive
      services, chronic disease rates, and engagement in health risk behaviors of
      participants with differing severities of disabilities to those without
      disabilities. This study was a secondary analysis of 2010 data collected in the
      Behavioral Risk Factor Surveillance System national survey in the United States.
      Rao Chi square test and logistic regression were employed. Participants with
      disabilities had significantly higher adjusted odds ratios for all chronic
      diseases, for physical inactivity, obesity and smoking. They were significantly
      more likely to participate in some preventive services (flu/pneumonia
      vaccination, HIV test) and significantly less likely to participate in other
      preventive services (mammogram, Pap test). Our findings suggest that people with
      disabilities are less able to fully participate in all preventive services
      offered.

PMID- 23121747
TI  - Multifaceted support for a new medical school in Nepal devoted to rural health by
      a Canadian Faculty of Medicine and Dentistry.
AB  - Nepal and Alberta are literally a world apart. Yet they share a common problem of
      restricted access to health services in remote and rural areas. In Nepal, urban
      rural disparities were one of the main issues in the recent civil war, which
      ended in 2006. In response to the need for improved health equity in Nepal a
      dedicated group of Nepali physicians began planning the Patan Academy of Health
      Sciences (PAHS), a new health sciences university dedicated to the education of
      rural health providers in the early 2000s. Beginning with a medical school the
      Patan Academy of Health Sciences uses international help to plan, deliver and
      assess its curriculum. PAHS developed an International Advisory Board (IAB)
      attracting international help using a model of broad, intentional recruitment and
      then on individuals' natural attraction to a clear mission of peace-making
      through health equity. Such a model provides for flexible recruitment of globally
      diverse experts, though it risks a lack of coordination. Until recently, the PAHS
      IAB has not enjoyed significant or formal support from any single international
      institution. However, an increasing number of the international consultants
      recruited by PAHS to its International Advisory Board are from the University of
      Alberta in Edmonton, Alberta, Canada (UAlberta). The number of UAlberta Faculty
      of Medicine and Dentistry members involved in the project has risen to fifteen,
      providing a critical mass for a coordinated effort to leverage institutional
      support for this partnership. This paper describes the organic growth of the
      UAlberta group supporting PAHS, and the ways in which it supports a sister
      institution in a developing nation.

PMID- 23121748
TI  - Barriers to participate in support groups for people living with HIV: a
      qualitative study with men receiving antiretroviral treatment in a HIV clinic in
      Mthatha, South Africa.
AB  - Support groups are the most common and popular way of providing social support
      for people living with HIV and AIDS (PLWHA). Nevertheless, HIV positive men are
      reluctant to attend support groups, and in most mixed gender support groups,
      women outnumber men. The study used a sample men accessing antiretroviral
      treatment (ART) from a HIV clinic in South Africa, to examine their perceptions
      of support groups and explore their reasons for nonparticipation in such groups.
      Five focus groups interviews were conducted with 50 HIV positive men. Their age
      ranged from 28-70 years, all had disclosed their HIV status to partners and
      family members and were receiving ART for more than a year. The main barriers for
      nonparticipation related to issues on support groups were; Unavailability of
      support groups in local communities which translated to, no access, the timing of
      meetings and lack of transport money. Fear of unintended disclosure of HIV status
      due to breach of confidentiality with resulting stigma and social rejection. On a
      personal level, participants felt that they had adequate support at home.
      Participants would consider participating if men only support groups are
      initiated, support groups are held on weekends, and they are provided with more
      information on support groups. Health care providers have a critical role to play
      in creating awareness of and education on the role of support groups for PLWHA.
      Support group planners should consider men only support groups which has been
      shown to have positive outcomes and facilitates member participation.

PMID- 23121749
TI  - Demand for child healthcare in Nigeria.
AB  - Nigeria with an estimated $350 per capital annually still ranks near the bottom
      158 out of 177 countries in the UN Human Capital Development Index in terms of
      per capita income, with more than half of the population living in poverty. Over
      the past decade U5MR is estimated to be 201 deaths/1000 lives births,the high
      rates of child mortality especially the 0-5 years shows the total breakdown of
      social and economic well-being of the country .This paper examined child health
      care demand in Nigeria using the Nested Multinomial Logit Model estimation
      technique.The study used parents' education as a proxy for child education,while
      the decision to make a choice of the health facilities was also assumed to be
      that of the House-Hold head. The study found out that female child has a higher
      probability of seeking health care facility ahead of their male counterpart.
      Also, the household head educational level was found to be a determinant of
      health care seeking behavior of the child. Empirical evidence also revealed that
      that the probability of seeking healthcare increases with household size and that
      demand for child health care in Nigeria is non linear in nature.Based on this,
      the paper recommends the need to show greater commitment to child health care and
      that government should reduce the problems militating against effective
      performance of the health sector such as, inefficiency, wasteful use of
      resources, low quality of service and poor enabling environment.

PMID- 23121750
TI  - An investigation of the stillbirths at a tertiary hospital in Limpopo province of
      South Africa.
AB  - OBJECTIVE: To determine the stillbirth rate and identify the causal factors
      associated with it in a tertiary hospital. METHODS: A retrospective review of
      records of women who had stillbirths at a tertiary hospital of the Limpopo
      Province was conducted. The study period was two years from January 1, 2009 to
      December 31, 2010. The hospital maternity registers were used to identify the
      women who gave birth during the study period. Data were collected using a data
      collection form designed for the study. The data collected included maternal age,
      parity, gestation, mode of delivery, obstetric complications, infant or foetal's
      gender and weight; whether the birth was fresh stillbirth or macerated and cause
      of stillbirth. RESULTS: There were 5597 deliveries during the two years period of
      the study. The hospital-based stillbirth rate was 38.4 per 1000 births, with 71%
      being macerated. The majority of women with stillborn infant in this study were
      in the age group (24%) 20-34 years, followed by (23%) aged 35 years and older.
      Nulliparity was associated with stillbirth. Unexplained intrauterine foetal
      death, hypertensive disease, placenta abruptio was the leading causes of
      stillbirth. CONCLUSION: In this study stillbirth rate seems to be unacceptably
      high, though less than those reported in other settings. The causal factors
      associated with it were identified as nulliparity, unexplained intrauterine
      foetal deaths, hypertensive disease, and placenta abruptio. Because of the high
      rate of stillbirths reported in this study, it is recommended that interventions
      be made to introduce fetal autopsies at the tertiary healthcare facilities and
      that an educational intervention aimed teaching pregnant women be instituted.

PMID- 23121751
TI  - Challenges and opportunities of US and Arab collaborations in health services
      research: a case study from Qatar.
AB  - Economic globalization and advances in technology have made it more feasible and
      even necessary to develop international research collaborations in global public
      health. Historically, collaborations in global research described in the
      literature have been mostly "North-South" collaborations in which the more
      developed "North" country works together with a developing "South" country to
      conduct research in the latter. This type of collaboration has for the most part,
      represented unequal partnership and rarely left behind a lasting impact.
      Recently, the opportunity for a new kind of international research partnership
      has emerged in which the host country has significant financial resources, but
      relatively limited expertise in research Methodology or techniques and research
      implementation.  This type of collaboration features a relative equalization of
      power between the international partners. The purpose of this paper is to
      describe the process of building a successful research collaboration between a
      team in the United States and a team in Qatar, a rich Arabic nation in Gulf. We
      present a case study that provides an overview of our own project focused on the
      development of a culturally and linguistically adapted health care quality
      instrument for Qatar, discussing many of the benefits and challenges we
      encountered during each phase of instrument development. We present
      recommendations for researchers seeking sustainable and equitable partnerships
      with the Arab World.

PMID- 23121752
TI  - Association between occupational stress and respiratory symptoms among lecturers
      in Universiti Putra Malaysia.
AB  - There was considerable evidence that a subject's psychological status may
      influence respiratory sensations and that some subjects may experience
      respiratory symptoms regardless of the presence of a respiratory disease. The
      objective of this study was to determine the association between occupational
      stress and respiratory symptoms among lecturers. This cross sectional study was
      conducted in Universiti Putra Malaysia, involved 61 lecturers from various
      faculties. Job Content Questionnaire (JCQ) and questionnaires based on American
      Thoracic Society were used to collect the data on socio-demography, stress level
      and respiratory symptoms. High level of occupational stress (high strain) was
      determined among 16 of the respondents (26.2%). Breathlessness was the common
      symptom experienced by the respondents. Female lecturers were significantly
      experienced high stress level compared to male (p=0.035). They were also
      significantly having more breathlessness symptom compared to male lecturer
      (p=0.011). Study highlighted in study population, gender plays a significant role
      that influenced level of occupational stress and also gender has role in
      resulting occupational stress level and respiratory symptoms. There was no
      significant association between occupational stress and respiratory symptoms. It
      can be concluded that this group of lecturers of Universiti Putra Malaysia did
      not experienced high occupational stress level. Occupational stress level was not
      statistically significantly associated with all respiratory symptoms being
      studied.

PMID- 23121753
TI  - Food polyamine and cardiovascular disease--an epidemiological study.
AB  - The purpose of this study was to examine the contribution of dietary polyamines
      toward preventing cardiovascular disease (CVD). Age-standardized mortality rates
      as well as other relevant information regarding individuals with CVD were
      gathered from the World Health Organization and the International Monetary Fund
      in 48 different European and other Western countries. Food supply data were
      collected from the database of the United Nations, and the amount of dietary
      polyamines was estimated by using polyamine concentrations in foods from
      published sources. The association between CVD mortality and the amount of
      polyamines was investigated by performing a series of multiple linear regression
      analyses. Analyses using factors known to modulate the risk of CVD including:
      Gross Domestic Product (GDP) (standardized regression coefficient (r) = -0.786, p
      < 0.001) and the amount of fruits, vegetable, nuts, and beans (r = -0.183, p =
      0.001) but not including polyamines, showed negative associations with CVD, while
      smoking rate (r = 0.139, p = 0.041) and whole milk amount (r = 0.131, p = 0.028)
      showed positive associations with CVD. When the amount of polyamines was added to
      the analyses as a covariate, GDP (r = -0.864, p < 0.001) and polyamines (r = 
      0.355, p = 0.007) showed negative associations with CVD, while smoking rate (r =
      0.183, p = 0.006) and whole milk (r = 0.113, p = 0.041) showed positive
      associations with CVD. The inverse association between dietary polyamines and CVD
      mortality revealed by the present study merits further evaluation.

PMID- 23121754
TI  - Brain damage treated with non proven intensive training 2003-2011: a Norwegian
      cost analysis.
AB  - OBJECTIVES: There has been an increased request for intensive training and
      rehabilitation of patients with brain damage in Norway. These programs are
      demanding with regard to personnel, travelling, time and economic resources. We
      aimed to indicate cost and gain to make these programs cost-effective. METHODS: A
      retrospective study included all patients referred to the Northern Norway
      Regional Health Authority (NNRHA) trust during the nine years period 2003-2011.
      All referrals to the NNRHA trust for the economic coverage of foreign based
      rehabilitation or habilitation programs (The Advanced Bio-Mechanical
      Rehabilitation (ABR), Institutes of Achievement of Human Potential program (IAHP)
      (Doman Method), Family Hope Center (FHC) program and the Kozijavkin Method) were
      included. 17 patients were detected and 15 fulfilled the inclusion criteria for
      funding. Median age was 8 years (1-31 years). Cost from the specialist health
      care point of view was calculated. A cut-off limit of ?57,000/quality adjusted
      life year (QALY) and a 4% discount rate was employed. RESULTS: The undiscounted
      cost per patient enrolled was calculated ?133,210 (discounted ?121,348). To make
      these therapies cost effective, a total of at least 2.13 QALYs (2.34 undiscounted
      QALYs) must be gained per patient enrolled. Such a gain could not be indicated
      and we doubt it is achievable. CONCLUSION: Non-proven intensive training programs
      for patients with brain damage are costly. As long as their effect has not been
      documented, health care services should not spend resources on these programs
      outside clinical trials.

PMID- 23121755
TI  - A review about the effect of life style modification on diabetes and quality of
      life.
AB  - The aim of this review is to examine diabetes and quality of life improvements
      through modifying life style. The data was collected by reviewing published
      articles from PubMed, Medline, Web of Science, and Google open access
      publications. The review identified prevention strategies can reduce the risk and
      complications of diabetes. Life style modification in relation to obesity, eating
      habit, and physical exercise can play a major role in the prevention of diabetes.
      Nowadays, there has been progress in the development of behavioural strategies to
      modify these life style habits and it is not easy to accept for long term basis.
      If people maintain a balanced diet and physical exercise this can have real and
      potential benefits for their prevention and control of complications from chronic
      diseases particularly for cardiovascular risk and diabetes. Healthy life style
      may best be achieved through public private partnerships involving government,
      partners organizations, health services providers, community and people living
      with diabetes. Effective strategies to reduce the incidence of diabetes globally
      and assist in managing the disease are urgently required.

PMID- 23121756
TI  - Evaluation of the antioxidant activity of three varieties of honey from different
      botanical and geographical origins.
AB  - It is well established that honey contains substantial antioxidant compounds that
      could protect cell components from the harmful action of free radicals. One can
      speculate that these compounds may strengthen the organism defenses and
      consequently prevent oxidative stress in humans. Therefore, over time, impaired
      cells can accumulate and lead to age-related diseases. A comparative study was
      carried out to assess the antioxidant activity of three varieties of honey from
      different botanical and geographical (Manuka honey from New Zealand, Acacia Honey
      from Germany and Wild carrot honey from Algeria). Manuka honey had the highest
      phenolic content with 899.09 +/- 11.75 mg gallic acid/kg. A strong correlation
      between the antioxidant activities of honeys and their total phenol contents has
      been noticed.

PMID- 23121757
TI  - Prevalence of analgesic prescriptions among patients with cancer in Japan: an
      analysis of health insurance claims data.
AB  - OBJECTIVES: To promote effective management of cancer pain as a nationwide health
      policy, it is necessary to monitor the performance of health care providers in
      managing pain in their patients. To plan a system that monitors the performance
      of pain management, the exact Methods of measurement, including the range of
      target patients, and estimate the resources must be defined. Performance in pain
      management can be evaluated either in all patients with cancer or restricted to
      patients with cancer who are already taking analgesics. Restricting the target
      patient group to patients on analgesics may be more efficient but the extent of
      that efficiency remains uncertain. METHODS: Using insurance claims from eight
      employer-sponsored insurance companies, we analyzed data from patients (N = 2858)
      who had received anti-cancer treatment (ie, surgery, chemotherapy, and radiation
      therapy) for the five major cancers in Japan (ie, breast, colorectal, liver,
      lung, and stomach cancers). RESULTS: Overall, 22.9% of patients received some
      kind of analgesic prescription in the course of a month. Lung cancer patients
      were more likely to be prescribed analgesic prescriptions (any analgesics 34.8%;
      opioids 18.2%) than patients with the other four cancers. The observed percentage
      of patients who received analgesic prescriptions over the study period (ie,
      January 2005 to November 2009) decreased. CONCLUSION: If we limit the target
      patient group to patients with cancer already on analgesics, we can reduce the
      number of persons to be contacted by about three-fourths, compared to assessing
      pain in all patients with cancer. Although we do not wish to ignore the problem
      of undetected pain among patients with cancer, beginning our systematic
      evaluation with patients with cancer already on analgesics may be a realistic
      option.

PMID- 23121758
TI  - Eating behaviors of older adults participating in government-sponsored programs
      with different demographic backgrounds.
AB  - The purpose of this study was to determine the food behaviors of nutritionally
      high-risk seniors as a function of their racial background, gender, marital
      status, and education level. A total of 69 seniors were identified to be at high
      nutritional risk using the Nutrition Screening Initiative (NSI) checklist. A
      supplemental questionnaire (SQ) was created to examine the risk factors in
      relation to the participant's demographic background. Key results indicated that
      Asians practiced healthy food behaviors and women were more likely to eat alone
      (p?0.05). Married participants (90.9%) were most likely to consume 2 meals or
      more each day. College educated individuals practiced healthier eating, eating 5
      servings or more of fruits and vegetables (p?0.01) and 2 or more servings of milk
      and milk products (p?0.01). These preliminary findings indicate that more studies
      should be conducted to focus on the demographic characteristics and food
      behaviors among older populations.

PMID- 23121759
TI  - Religious attitudes in adolescents with Obsessive Compulsive Symptoms OCS and
      disorder OCD.
AB  - BACKGROUND: Mental health professionals observed booming in prevalence of
      obsessive compulsive symptoms among children and adolescents. Our epidemiological
      study aims at estimating the prevalence of obsessive symptoms and obsessive
      compulsive disorder among secondary school students and, as a secondary research
      objective, to assess religious attitudes among those patients. MATERIALS: The
      study is cross sectional conducted on 1299 secondary school students, adequate
      sample size estimated on a prevalence of 2% for Obsessive Compulsive Disorder
      (OCD) in literature. Equal samples were recruited from the 3 educative zones in
      Alexandria Governorate. Obsessive compulsive symptoms were assessed by the Lyeton
      obsessive inventory child LOI-CV, the Arabic version that has been validated and
      tested for reliability in Egyptian culture. Those scoring 35 or above were
      subjected to the Mini International Neuropsychiatric Interview for children MINI
      KID Arabic. Patients with OCD had their diagnosis confirmed by psychiatric
      interview to assure fulfillment of criteria of OCD according to DSM IV -TR
      criteria. A standardized self reporting questionnaire was designed to assess
      religious attitudes. RESULTS: Among the studied sample (n=1299), 201 students
      were scored > 35 on LOI-CV i.e. 15.5% of the total sample have OCS The prevalence
      of OCD among studied sample was 2.2% as 29 students from the OCS students were
      fulfilling diagnostic criteria for OCD according to DSM-IV TR. Religious
      practicing attitudes were 93.1% and 79.6% in adolescents with obsessive
      compulsive disorder OCD and obsessive compulsive symptoms OCS respectively with
      no difference (X2=0.07). CONCLUSION: There's a high prevalence rate of obsessive
      symptoms among adolescents, such finding highlights the necessity and need of
      public awareness and screening of adolescents for early detection and management.
      Religious attitude didn't show significant difference among adolescents showing
      only obsessive compulsive disorder or those showing only obsessive compulsive
      symptoms.

PMID- 23121760
TI  - How evidence-based is an 'evidence-based parenting program'? A PRISMA systematic
      review and meta-analysis of Triple P.
AB  - BACKGROUND: Interventions to promote positive parenting are often reported to
      offer good outcomes for children but they can consume substantial resources and
      they require rigorous appraisal. METHODS: Evaluations of the Triple P parenting
      program were subjected to systematic review and meta-analysis with analysis of
      biases. PsychInfo, Embase and Ovid Medline were used as data sources. We selected
      published articles reporting any child-based outcome in which any variant of
      Triple P was evaluated in relation to a comparison condition. Unpublished data,
      papers in languages other than English and some book chapters were not examined.
      Studies reporting Eyberg Child Behavior Inventory or Child Behavior Checklist
      scores as outcomes were used in the meta-analysis. RESULTS: A total of 33
      eligible studies was identified, most involving media-recruited families. Thirty
      one of these 33 studies compared Triple P interventions with waiting list or no
      treatment comparison groups. Most papers only reported maternal assessments of
      child behavior. Twenty-three papers were incorporated in the meta-analysis. No
      studies involved children younger than two-years old and comparisons of
      intervention and control groups beyond the duration of the intervention were only
      possible in five studies. For maternally-reported outcomes the summary effect
      size was 0.61 (95%CI 0.42, 0.79). Paternally-reported outcomes following Triple P
      intervention were smaller and did not differ significantly from the control
      condition (effect size 0.42 (95%CI -0.02, 0.87)). The two studies involving an
      active control group showed no between-group differences. There was limited
      evidence of publication bias, but there was substantial selective reporting bias,
      and preferential reporting of positive results in article abstracts. Thirty-two
      of the 33 eligible studies were authored by Triple-P affiliated personnel. No
      trials were registered and only two papers contained conflict of interest
      statements. CONCLUSIONS: In volunteer populations over the short term, mothers
      generally report that Triple P group interventions are better than no
      intervention, but there is concern about these results given the high risk of
      bias, poor reporting and potential conflicts of interest. We found no convincing
      evidence that Triple P interventions work across the whole population or that any
      benefits are long-term. Given the substantial cost implications, commissioners
      should apply to parenting programs the standards used in assessing pharmaceutical
      interventions. See related commentary: http://www.biomedcentral.com/1741
      7015/10/145.

PMID- 23121761
TI  - Trade-off of dynamic fragility but not of robustness in metabolic pathways in
      silico.
AB  - Selective robustness is a key feature of biochemical networks. It confers a
      fitness benefit to organisms living in dynamic environments. The (in-)sensitivity
      of a network to external perturbations results from the interplay between network
      dynamics, structure and enzyme kinetics. In this work, we focus on the subtle
      interplay between robustness and control (fragility). We describe a quantitative
      method for defining the fragility and robustness of system fluxes to
      perturbations. We find that for many mathematical models of metabolic pathways,
      the robustness of fluxes vis-a-vis perturbations of all the enzyme activities is
      captured by a broad distribution of the robustness coefficients. We find that in
      cases where a metabolic pathway flux is made less robust with respect to the
      perturbation of a particular network step, the average robustness may still be
      increased. We then show that fragility is conserved upon a perturbation of
      network processes and equate fragility with control as defined in metabolic
      control analysis. This highlights the non-intuitive nature of the interplay
      between fragility and robustness and the need for a dynamic network
      understanding.

PMID- 23121762
TI  - Outpatient red blood cell transfusion payments among patients on chronic
      dialysis.
AB  - BACKGROUND: Payments for red blood cell (RBC) transfusions are separate from US
      Medicare bundled payments for dialysis-related services and medications. Our
      objective was to examine the economic burden for payers when chronic dialysis
      patients receive outpatient RBC transfusions. METHODS: Using Truven Health
      MarketScan(r) data (1/1/02-10/31/10) in this retrospective micro-costing economic
      analysis, we analyzed data from chronic dialysis patients who underwent at least
      1 outpatient RBC transfusion who had at least 6 months of continuous enrollment
      prior to initial dialysis claim and at least 30 days post-transfusion follow-up.
      A conceptual model of transfusion-associated resource use based on current
      literature was employed to estimate outpatient RBC transfusion payments. Total
      payments per RBC transfusion episode included screening/monitoring (within 3
      days), blood acquisition/administration (within 2 days), and associated
      complications (within 3 days for acute events; up to 45 days for chronic events).
      RESULTS: A total of 3283 patient transfusion episodes were included; 56.4% were
      men and 40.9% had Medicare supplemental insurance. Mean (standard deviation [SD])
      age was 60.9 (15.0) years, and mean Charlson comorbidity index was 4.3 (2.5).
      During a mean (SD) follow-up of 495 (474) days, patients had a mean of 2.2 (3.8)
      outpatient RBC transfusion episodes. Mean/median (SD) total payment per RBC
      transfusion episode was $854/$427 ($2,060) with 72.1% attributable to blood
      acquisition and administration payments. Complication payments ranged from mean
      (SD) $213 ($168) for delayed hemolytic transfusion reaction to $19,466 ($15,424)
      for congestive heart failure. CONCLUSIONS: Payments for outpatient RBC
      transfusion episodes were driven by blood acquisition and administration
      payments. While infrequent, transfusion complications increased payments
      substantially when they occurred.

PMID- 23121763
TI  - Implementation of evidence-based practices in the context of a redevelopment
      project in a Canadian healthcare organization.
AB  - PURPOSE: The recent introduction of a project management office (PMO) in a major
      healthcare center, led by a nurse, provides a unique opportunity to understand
      how a PMO facilitates successful implementation of evidence-based practices in
      care delivery. DESIGN: A case study with embedded units (individuals, projects,
      and organization). In this study, the case is operationally defined as the PMO
      deployed in a Canadian healthcare center. METHODS: The sources of evidence used
      in this study were diverse. They consisted of 38 individual interviews, internal
      documents, and administrative data. The data were collected from March 2009 to
      November 2011. Content analysis was used to analyze the qualitative data.
      FINDINGS: PMO experts help improve practices, and the patients thus receive safer
      and better quality care. Several participants point out that they could not make
      the changes without the PMO's support. They mention that they succeeded in
      changing their practices based on the evidence and acquired knowledge of change
      management with the PMO members that can be transferred to their practice.
      CONCLUSIONS: With the leadership of the nurse director of the PMO, members
      provide a range of expertise and fields in evidence-based change management,
      project management, and evaluation. CLINICAL RELEVANCE: PMO facilitates the
      implementation of clinical and organizational practices based on evidence to
      improve the quality and safety of care provided to patients.

PMID- 23121764
TI  - The H-factor as a novel quality metric for homology modeling.
AB  - BACKGROUND: Drug discovery typically starts with the identification of a
      potential target that is then tested and validated either through high-throughput
      screening against a library of drug compounds or by rational drug design. When
      the putative target is a protein, the latter approach requires the knowledge of
      its structure. Finding the structure of a protein is however a difficult task.
      Significant progress has come from high-resolution techniques such as X-ray
      crystallography and NMR; there are many proteins however whose structure have not
      yet been solved. Computational techniques for structure prediction are viable
      alternatives to experimental techniques for these cases. However, the proper
      validation of the structural models they generate remains an issue. FINDINGS: In
      this report, we focus on homology modeling techniques and introduce the H-factor,
      a new indicator for assessing the quality of protein structure models generated
      with these techniques. The H-factor is meant to mimic the R-factor used in X-ray
      crystallography. The method for computing the H-factor is fully described with a
      demonstration of its effectiveness on a test set of target proteins. CONCLUSIONS:
      We have developed a web service for computing the H-factor for models of a
      protein structure. This service is freely accessible at
      http://koehllab.genomecenter.ucdavis.edu/toolkit/h-factor.

PMID- 23121765
TI  - The USCACA hosted symposiums at the 7th CACA annual meeting and the 15th CSCO
      annual meeting in Beijing.
AB  - In September 2012, the US Chinese Anti-Cancer Association (USCACA) hosted two
      symposiums in Beijing. The USCACA hosted the first joint session at the 7th
      annual meetings of the Chinese Anti-Cancer Association (CACA), themed on
      "Collaboration between the US and China in Cancer Research." Six experts from the
      United States and China presented their latest work on basic and translational
      cancer research. During this symposium, 5 young Chinese scholars, returnees after
      their training in the United States, were honored the"AFCR-USCACA Scholarships
      Award." The USCACA hosted a second symposium during the 15th annual meeting of
      the Chinese Society of Clinical Oncology (CSCO), focused on the "US-China
      Collaboration in Cancer Drug Clinical Development." An international delegation
      of oncology experts presented the innovative clinical trial strategies and
      discussed the biomarkers for cancer early detection and clinical trials, targeted
      therapy, and new drug development. The Oncology Drug Clinical Development and
      Safety Evaluation Committee was also launched to promote an innovative
      environment and to provide a collaborative platform for anti-cancer drug
      development in China.

PMID- 23121766
TI  - Using lithium as a neuroprotective agent in patients with cancer.
AB  - Neurocognitive impairment is being increasingly recognized as an important issue
      in patients with cancer who develop cognitive difficulties either as part of
      direct or indirect involvement of the nervous system or as a consequence of
      either chemotherapy-related or radiotherapy-related complications. Brain
      radiotherapy in particular can lead to significant cognitive defects.
      Neurocognitive decline adversely affects quality of life, meaningful employment,
      and even simple daily activities. Neuroprotection may be a viable and realistic
      goal in preventing neurocognitive sequelae in these patients, especially in the
      setting of cranial irradiation. Lithium is an agent that has been in use for
      psychiatric disorders for decades, but recently there has been emerging evidence
      that it can have a neuroprotective effect.This review discusses neurocognitive
      impairment in patients with cancer and the potential for investigating the use of
      lithium as a neuroprotectant in such patients.

PMID- 23121767
TI  - EGR1 is critical for gastrin-dependent upregulation of anion exchanger 2 in
      gastric cancer cells.
AB  - The essential anion exchanger (AE) involved in bicarbonate secretion is
      AE2/SLC4A2, a membrane protein recognized to be relevant for the regulation of
      the intracellular pH in several cell types. Here we report that gastrin, a major
      gastrointestinal hormone, upregulates the expression of AE2 mRNA and protein in a
      cholecystokinin B receptor dependent manner in gastric cancer cells. The
      upregulated species of AE2 mRNA originates from the classical upstream promoter
      of the AE2 gene (here referred to as AE2a1) which provides the binding site for
      transcription factors early growth response 1 (EGR1) and SP1. EGR1 upregulated
      the AE2 expression that can be competitively inhibited by SP1 in co-transfection
      experiments. This competitive inhibition was avoided in cells because the SP1
      expression was time-staggered to EGR1 in response to gastrin. Overexpression or
      knockdown of EGR1 consistently increased or decreased the expression of AE2. Our
      data linked a novel signal pathway involved in gastrin-stimulated AE2 expression.

PMID- 23121768
TI  - A randomised controlled trial of Heparin versus EthAnol Lock THerapY for the
      prevention of Catheter Associated infecTion in Haemodialysis patients--the
      HEALTHY-CATH trial.
AB  - BACKGROUND: Tunnelled central venous dialysis catheter use is significantly
      limited by the occurrence of catheter-related infections. This randomised
      controlled trial assessed the efficacy of a 48 hour 70% ethanol lock vs heparin
      locks in prolonging the time to the first episode of catheter related blood
      stream infection (CRBSI). METHODS: Patients undergoing haemodialysis (HD) via a
      tunnelled catheter were randomised 1:1 to once per week ethanol locks (with two
      heparin locks between other dialysis sessions) vs thrice per week heparin locks.
      RESULTS: Observed catheter days in the heparin (n=24) and ethanol (n=25) groups
      were 1814 and 3614 respectively. CRBSI occurred at a rate of 0.85 vs. 0.28 per
      1000 catheter days in the heparin vs ethanol group by intention to treat analysis
      (incident rate ratio (IRR) for ethanol vs. heparin 0.17; 95%CI 0.02-1.63;
      p=0.12). Flow issues requiring catheter removal occurred at a rate of 1.6 vs 1.4
      per 1000 catheter days in the heparin and ethanol groups respectively (IRR 0.85;
      95% CI 0.20-3.5 p =0.82 (for ethanol vs heparin). CONCLUSIONS: Catheter survival
      and catheter-related blood stream infection were not significantly different but
      there was a trend towards a reduced rate of infection in the ethanol group. This
      study establishes proof of concept and will inform an adequately powered
      multicentre trial to definitively examine the efficacy and safety of ethanol
      locks as an alternative to current therapies used in the prevention of catheter
      associated blood stream infections in patients dialysing with tunnelled
      catheters. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry
      ACTRN12609000493246.

PMID- 23121769
TI  - Hypertension management: rationale for triple therapy based on mechanisms of
      action.
AB  - An estimated 25% of patients will require 3 antihypertensive agents to achieve
      blood pressure (BP) control; combination therapy is thus an important strategy in
      hypertension treatment. This review discusses the triple-therapy combination of
      an angiotensin receptor blocker (ARB) or direct renin antagonist (DRI) with a
      calcium channel blocker (CCB) and a diuretic, with a focus on mechanisms of
      action. Multiple physiologic pathways contribute to hypertension. Combining
      antihypertensive agents not only better targets the underlying pathways, but also
      helps blunt compensatory responses that may be triggered by single-agent therapy.
      DRIs and ARBs target the renin-angiotensin-aldosterone system (RAAS) at the
      initial and final steps, respectively, and both classes lower BP by reducing the
      effects of angiotensin-2; however, ARBs may trigger a compensatory increase in
      renin activity. Dihydropyridine CCBs target L-type calcium channels and lower BP
      through potent vasodilation, but can trigger compensatory activation of the
      sympathetic nervous system (SNS) and RAAS. Thiazide diuretics lower BP initially
      through sodium depletion and plasma volume reduction, followed by total
      peripheral resistance reduction, but can also trigger compensatory activation of
      the SNS and RAAS. The combination of an agent targeting the RAAS with a CCB and
      diuretic is rational, and triple combinations of
      valsartan/amlodipine/hydrochlorothiazide,
      olmesartan/amlodipine/hydrochlorothiazide, and
      aliskiren/amlodipine/hydrochlorothiazide have demonstrated greater effectiveness
      compared with their respective dual-component combinations. In addition, single
      pill, fixed-dose combinations can address barriers to BP control including
      clinical inertia and poor adherence. Fixed-dose antihypertensive combination
      products capitalize on complementary mechanisms of action and have been shown to
      result in improved BP control.

PMID- 23121770
TI  - Call for papers: examination of basic nursing care.

PMID- 23121772
TI  - Commentary on a recent review of lithium toxicity: what are its implications for
      clinical practice?
AB  - A recent paper by McKnight et al. in The Lancet has provided the first formal
      meta-analysis of the more common adverse reactions to lithium. The authors
      analyzed 385 studies and focused mainly on the harmful effects of lithium on the
      kidney, the thyroid and parathyroid glands, body weight, skin and congenital
      malformations. Their contribution is important and welcome, but as a guide for
      practice, it needs to be complemented by other relevant observations and
      individual patient-focused perspectives.The findings from that meta-analysis
      somewhat underestimate the renal side-effects, and distort to some degree or
      exclude other adverse effects. The glomerular filtration rate is reduced but not
      more than 0 to 5 ml/min/year of observation; this may not fully reflect the
      present state of knowledge. A quarter of patients in the study had abnormalities
      of the thyroid and/or parathyroid gland, and lithium was found to increase body
      weight significantly less than did olanzapine. Unfortunately, the authors did not
      consider the observations from spontaneous reporting systems, which may have
      changed the picture.We feel that some specific limitations of the study were
      related to the inclusion of patients regardless of adequacy of treatment, quality
      of monitoring, drug combinations, age and sex, and stabilization response.

PMID- 23121773
TI  - The influence of oral antidiabetic drugs on cellular drug uptake mediated by
      hepatic OATP family members.
AB  - As patients with type 2 diabetes receiving oral antidiabetic drugs are often
      concomitantly treated with other drugs, they are of increased risk for drug
      interactions. Drugs have to be taken up into hepatocytes before their
      intracellular drug action or before they are metabolized, and therefore, uptake
      transporters are important modulators of drug pharmacokinetics and drug effects.
      To gain more insights into the role of uptake transporters for drug interactions,
      we investigated whether frequently prescribed oral antidiabetic drugs interact
      with the transport of drugs, mediated by the hepatic uptake transporters OATP1B1
      (gene symbol SLCO1B1), OATP1B3 (gene symbol SLCO1B3) and OATP2B1 (gene symbol
      SLCO2B1). Using HEK293 cells recombinantly over-expressing these uptake
      transporters, we analysed whether glibenclamide, glimepiride, nateglinide and
      pioglitazone influence the transport of the model transport substrate
      bromosulfophthalein. Furthermore, we investigated the influence of the same oral
      antidiabetic drugs and of repaglinide and rosiglitazone on the uptake of the HMG
      CoA-reductase inhibitor atorvastatin. The oral antidiabetic drugs glibenclamide,
      glimepiride and nateglinide inhibited the transport of the model substrate
      bromosulfophthalein, particularly the OATP2B1-mediated uptake. The OATP-mediated
      atorvastatin uptake was inhibited in a similar manner. For glibenclamide,
      inhibitory constants (Ki values) of 13.6 MUM, 8.1 MUM and 0.5 MUM for OATP1B1-,
      OATP1B3- and OATP2B1-mediated BSP uptake were determined. In conclusion, these in
      vitro results demonstrate that several oral antidiabetic drugs may influence
      hepatic OATP-mediated drug uptake. The in vivo consequences of these results have
      to be analysed in further studies.

PMID- 23121774
TI  - Trends in the pharmacological treatment of osteoporosis in Spain from 2000 to
      2008.
AB  - AIM: To analyze the time trends in anti-osteoporosis medications consumption in
      Spain between 2000 and 2008 and the influence on such consumption induced by the
      Information Sheets related to the safety of menopausal hormone therapy and
      strontium ranelate published by the Spanish Agency of Medicines and Health
      Products (AEMPS). METHODS: Purchase data of anti-osteoporosis medications from
      2000 to 2008 were obtained from the Spanish Ministry of Health. This information
      includes the pharmacy sales data of medicinal products reimbursed by the Spanish
      National Health Service. Anti-osteoporosis medications consumption data were
      expressed as defined daily dose per 1 000 inhabitants per day in women aged 50 or
      more. RESULTS: During the study period, anti-osteoporosis medications consumption
      showed a continuous increase. The greatest increase was observed with
      bisphosphonates, particularly alendronate and risedronate in their weekly
      formulations. Strontium ranelate consumption was low but continuously increased
      and new information concerning its safety in 2007 had no effect on its
      consumption. The use of menopausal hormone therapy remained stable until 2003,
      and from then presented a continuous decrease until 2008. Raloxifene utilization
      increased from 2000 to 2004 and decreased thereafter. Calcitonin utilization
      decreased uninterruptedly and teriparatide was infrequently used. CONCLUSION:
      This study reports a marked change in osteoporosis treatment in Spain, which
      includes an important increase in anti-osteoporosis medication use, particularly
      of bisphosphonates and a decrease in menopausal hormone therapy use secondary to
      the new information about their safety.

PMID- 23121775
TI  - Effects of decision making on landing mechanics as a function of task and sex.
AB  - BACKGROUND: Factors that contribute to sex-differences in the incidence of
      anterior cruciate ligament injuries among athletes are not well understood. Of
      interest is whether decision making during landing influences biomechanical
      factors associated with anterior cruciate ligament injury. This study examined
      the effects of decision making on the mechanics of two-footed landing tasks in
      women and men. METHODS: Twenty-nine healthy young adults (13 women, 16 men)
      completed drop landings and drop-jumps under preplanned and decision-making
      conditions. Biomechanical data were collected and effects of decision making on
      lower extremity kinematics and kinetics were examined as a function of task and
      sex. FINDINGS: Landing mechanics were influenced by decision-making condition,
      task, and sex. During drop-jumps, participants exhibited lesser hip flexion (-3.3
      degrees ), lesser knee flexion (-5.1 degrees ), and greater knee abduction (+1.0
      degrees ) at initial contact under decision-making conditions. Under decision
      making conditions, no differences were observed in these variables between tasks
      or with respect to preplanned drop landings. Across tasks and sexes, participants
      exhibited greater ankle plantarflexion at initial contact (+1.6 degrees ),
      greater peak knee external rotation (+1.5 degrees ), lesser peak knee internal
      rotation (-1.0 degrees ), and smaller hip adduction moments (-0.2% body
      weight*height) under decision-making conditions. Women but not men exhibited
      smaller ankle inversion moments (-0.1% body weight*height) under decision-making
      conditions. INTERPRETATION: Modifications in landing mechanics suggest a default
      towards the preplanned drop landing strategy under decision-making conditions.
      Across sexes, drop landings and drop-jumps may be no more dangerous under
      decision-making conditions, with respect to anterior cruciate ligament loading,
      than preplanned drop landings.

PMID- 23121776
TI  - Redistribution of knee stress using laterally wedged insole intervention: Finite
      element analysis of knee-ankle-foot complex.
AB  - BACKGROUND: Laterally wedged insoles are widely applied in the conservative
      treatment for medial knee osteoarthritis. Experimental studies have been
      conducted to understand the effectiveness of such an orthotic intervention.
      However, the information was limited to the joint external loading such as knee
      adduction moment. The internal stress distribution is difficult to be obtained
      from in vivo experiment alone. Thus, a three-dimensional finite element model of
      the human knee-ankle-foot complex, together with orthosis, was developed in this
      study and used to investigate the redistribution of knee stress using laterally
      wedged insole intervention. METHODS: Laterally wedged insoles with wedge angles
      of 0, 5, and 10 degrees  were fabricated for intervention. The subject-specific
      geometry of the lower extremity with details was characterized in the
      reconstruction of MR images. Motion analysis data and muscle forces were input to
      drive the model. The established finite element model was employed to investigate
      the loading responses of tibiofemoral articulation in three wedge angle
      conditions during simulated walking stance phase. FINDINGS: With either of the 5
      degrees  or 10 degrees  laterally wedged insole, significant decreases in von
      Mises stress and contact force at the medial femur cartilage region and the
      medial meniscus were predicted comparing with the 0 degrees  insole.
      INTERPRETATION: The diminished stress and contact force at the medial compartment
      of the knee joint demonstrate the immediate effect of the laterally wedged
      insoles. The intervention may contribute to medial knee osteoarthritis
      rehabilitation.

PMID- 23121777
TI  - The effects of avoidance coping and coping self-efficacy on eating disorder
      attitudes and behaviors: a stress-diathesis model.
AB  - The present study employed a series of stress-diathesis models to examine whether
      avoidance coping and poor coping self-efficacy contribute to disordered eating
      attitudes and behaviors in a sample of college students. The sample included one
      hundred fifteen undergraduate students (28.7% male; 71.3% female). Participants
      completed self-report measures to assess daily stressors, coping style, coping
      self-efficacy, and eating disorder attitudes and behaviors. As predicted, among
      students with an avoidance coping style, those who reported more daily stressors
      exhibited higher eating disorder attitudes and behaviors than those with less
      daily hassles. Contrary to study hypothesis, number of daily hassles did not
      moderate the association between coping self-efficacy and eating disorder
      attitudes and behaviors. However, there was a significant main effect for coping
      self-efficacy, suggesting that students who lack confidence in their coping
      abilities are more likely to have problematic eating attitudes and behaviors,
      regardless of their level of daily stress. Clinically, results suggest that
      students who enter college with an avoidance coping style and poor coping self
      efficacy may be at risk for disordered eating, particularly with the onset of
      associated stress. Teaching students active problem-focused coping skills to deal
      with daily hassles associated with college life, and providing opportunities for
      repeated practice to bolster self-efficacy, may help prevent and/or reduce
      disordered eating attitudes and behaviors.

PMID- 23121771
TI  - Research needs in allergy: an EAACI position paper, in collaboration with EFA.
AB  - In less than half a century, allergy, originally perceived as a rare disease,
      has become a major public health threat, today affecting the lives of more than
      60 million people in Europe, and probably close to one billion worldwide, thereby
      heavily impacting the budgets of public health systems. More disturbingly, its
      prevalence and impact are on the rise, a development that has been associated
      with environmental and lifestyle changes accompanying the continuous process of
      urbanization and globalization. Therefore, there is an urgent need to prioritize
      and concert research efforts in the field of allergy, in order to achieve
      sustainable results on prevention, diagnosis and treatment of this most prevalent
      chronic disease of the 21st century.The European Academy of Allergy and Clinical
      Immunology (EAACI) is the leading professional organization in the field of
      allergy, promoting excellence in clinical care, education, training and basic and
      translational research, all with the ultimate goal of improving the health of
      allergic patients. The European Federation of Allergy and Airways Diseases
      Patients' Associations (EFA) is a non-profit network of allergy, asthma and
      Chronic Obstructive Pulmonary Disorder (COPD) patients' organizations. In support
      of their missions, the present EAACI Position Paper, in collaboration with EFA,
      highlights the most important research needs in the field of allergy to serve as
      key recommendations for future research funding at the national and European
      levels.Although allergies may involve almost every organ of the body and an array
      of diverse external factors act as triggers, there are several common themes that
      need to be prioritized in research efforts. As in many other chronic diseases,
      effective prevention, curative treatment and accurate, rapid diagnosis represent
      major unmet needs. Detailed phenotyping/endotyping stands out as widely required
      in order to arrange or re-categorize clinical syndromes into more coherent,
      uniform and treatment-responsive groups. Research efforts to unveil the basic
      pathophysiologic pathways and mechanisms, thus leading to the comprehension and
      resolution of the pathophysiologic complexity of allergies will allow for the
      design of novel patient-oriented diagnostic and treatment protocols. Several
      allergic diseases require well-controlled epidemiological description and
      surveillance, using disease registries, pharmacoeconomic evaluation, as well as
      large biobanks. Additionally, there is a need for extensive studies to bring
      promising new biotechnological innovations, such as biological agents, vaccines
      of modified allergen molecules and engineered components for allergy diagnosis,
      closer to clinical practice. Finally, particular attention should be paid to the
      difficult-to-manage, precarious and costly severe disease forms and/or
      exacerbations. Nonetheless, currently arising treatments, mainly in the fields of
      immunotherapy and biologicals, hold great promise for targeted and causal
      management of allergic conditions. Active involvement of all stakeholders,
      including Patient Organizations and policy makers are necessary to achieve the
      aims emphasized herein.

PMID- 23121778
TI  - The natural course of eating pathology in female university students.
AB  - This study investigated the natural course of eating pathology in a sample of
      female university students. Seventy-nine students were recruited in their first
      month of the university, 24 of whom endorsed objective binge eating and
      inappropriate compensatory behaviors based on an initial screening interview.
      Testing sessions occurred every 6 months for the following 2 1/2 years and
      included the assessment of eating pathology, general psychopathology and well
      being, weight, and exposure to psychological or psychiatric treatment. Data were
      analyzed using a mixed-effects linear regression model. Whereas general
      psychopathology decreased during the study, eating pathology was fairly stable.
      The symptomatic participants experienced significantly more weight fluctuations
      over the course of the study than did in the control participants. None of the
      symptomatic participants sought treatment for their eating and eating pathology
      showed little evidence of spontaneous remission. Larger, follow-up studies of
      changes to untreated eating pathology over time are recommended.

PMID- 23121779
TI  - Norms and discriminative validity of the Eating Disorder Examination
      Questionnaire (EDE-Q).
AB  - The first aim of this study was to provide norms for the Eating Disorder
      Examination Questionnaire (EDE-Q) in a diverse and large clinical sample of
      individuals with an eating disorder (ED), and a general population sample without
      an ED. Norms for individuals with obesity without an ED were also provided, as a
      more relevant comparison group for individuals with binge eating disorder. The
      second aim was to investigate the discriminative validity of the EDE-Q. A sample
      of females with an ED (N=935), women from the general population without an ED
      (N=235), and obese females without an ED (N=321) completed the EDE-Q. Explorative
      factor analyses did not support the theorized four subscales of the EDE-Q. Norms
      for EDE-Q global scores were provided for each of the three samples. Within the
      ED sample, norms were provided separately for patients with different ED
      diagnoses. Receiver operating characteristic analyses showed the EDE-Q global
      score to be highly accurate in discriminating individuals with an ED from those
      without, and moderately accurate in discriminating individuals with binge eating
      disorder from those with obesity. The presented norms contribute to a more
      accurate interpretation of EDE-Q scores, providing an index of the severity level
      of ED psychopathology. Furthermore, these norms can be used to assess clinical
      significant change during treatment. In addition, this study demonstrates that
      the EDE-Q, when using its global score, is a valid instrument to assess levels of
      ED psychopathology.

PMID- 23121780
TI  - Simultaneous and sequential comparisons of food quantity and consumption.
AB  - Two experiments explored how food-quantity comparisons affect judgments of food
      quantity and consumption. In Experiment 1, participants viewed drawings of
      portions of mashed potatoes presented either simultaneously or sequentially and
      later recalled sizes from memory. The observed biases in memory for size were
      consistent with previous research on the biases in judgments of the sizes of
      geometric shapes when shapes were presented simultaneously or sequentially. In
      Experiment 2, participants viewed two serving bowls of pasta salad presented
      either simultaneously or sequentially and consumed as much or as little as they
      wished from the smaller bowl. Consistent with previous findings suggesting that
      the quantities people consume are inversely related to biases in judgments of
      quantity, the effects observed in Experiment 1 were flipped in Experiment 2.
      These results suggest that food consumption is likely to be affected by
      comparison quantities and the effects of comparison quantities will depend on
      whether quantities are presented simultaneously or sequentially.

PMID- 23121781
TI  - Reward-sensitive women overeat in a varied food environment, but only when
      hungry.
AB  - In the current study we tried to elucidate the relationship between a personality
      trait, reward sensitivity, and an environmental variable; food variety. Based on
      scarce previous research we predicted that reward sensitivity would interact with
      variety in the food environment so that especially high reward sensitive
      individuals would be vulnerable to overeating in a varied food environment. It
      turned out that especially the high reward individuals did indeed overeat in a
      varied food environment. However, this was only the case for the highly reward
      sensitive individuals who experienced feelings of hunger. In other words, reward
      sensitivity does not affect food intake in varied food environments as long as
      feelings of hunger are not present. Future research should concentrate on
      identifying other factors that interact with the person and the environment to
      discourage reward-related overeating.

PMID- 23121782
TI  - Relationships between self-esteem, media influence and drive for thinness.
AB  - The media is a powerful societal tool for expressing expectations about how men
      and women should look. As a result, over the past several years, women have shown
      an increase in body dissatisfaction (Cash, Morrow, Hrabosky, & Perry, 2004). The
      present study examined the relationships between drive for thinness, self-esteem,
      and media influence among men and women. Two hundred ninety-four college students
      completed the Texas Social Behavior Inventory (Helmreich & Stapp, 1974),
      Sociocultural Attitudes towards Appearance Scale-3 (Thompson, van den Berg,
      Roehrig, Guarda, & Hienberg, 2004), self-constructed questionnaire influence of
      media models, and the drive for Thinness Subscale (DT) from the Eating Disorder
      Inventory-3 (EDI-3; (Garner, 2004)). We expected to find an association between
      drive for thinness and media influence and between drive for thinness and self
      esteem for both men and women. Finally, we expected that the use of media, social
      pressures and media internalization would be predictors of drive for thinness. We
      found a relationship between media influence and drive for thinness. There was
      also a relationship between self-esteem and drive for thinness. For both men and
      women, media models were the primary predictor for drive for thinness. However,
      for women the secondary predictor was social pressures; whereas for men the
      secondary predictor was internalization. Such findings show the importance of
      examining the impact of media sources on men and women in order to entangle
      gender differences.

PMID- 23121783
TI  - Evaluation of a new measure of mood intolerance, the Tolerance of Mood States
      Scale (TOMS): psychometric properties and associations with eating disorder
      symptoms.
AB  - OBJECTIVE: This research aimed to (i) validate a new measure of mood intolerance,
      the Tolerance of Mood States (TOMS) scale, and (ii) to examine associations
      between TOMS scores and eating pathology. METHODS: The original TOMS was
      developed and evaluated using the data from 258 adult participants. The measure
      consisted of two separate scales, initially with a total of 64 items, with this
      reduced to 34 items through exploratory factor analyses. The 34-item TOMS was
      administered to a new sample of adult participants recruited from a university
      setting (N=227), along with the Distress Tolerance Scale (DTS-C; Corstorphine,
      Mountford, Tomlinson, Waller, & Meyer, 2007) and other measures of psychological
      distress and eating disorder symptoms. The reliability and validity of the 34
      item TOMS scales were examined through confirmatory factor analysis, inspection
      of alpha coefficients, and inspection of correlations between TOMS scores and
      those on other relevant measures. Associations between TOMS scores and eating
      disorder symptoms were considered using continuous and categorical analyses.
      RESULTS: Analyses provided support for the reliability and validity of the scale
      two of the TOMS. This scale consists of 11 items on two subscales, and assesses
      the tendency to engage in maladaptive behaviours when confronted with intense
      moods. Scores on this scale were significantly higher amongst participants who
      reported binge eating and purging than amongst participants who did not, and they
      correlated significantly with a global index of eating disorder symptoms. The 11
      item scale was retained as the final version of the TOMS. CONCLUSIONS:
      Preliminary support is provided for the validity of a new measure of mood
      intolerance, the TOMS. Scores on the TOMS subscales were significantly associated
      with eating disorder symptoms in this non-clinical sample.

PMID- 23121784
TI  - A prospective study of the influence of the UPPS model of impulsivity on the co
      occurrence of bulimic symptoms and non-suicidal self-injury.
AB  - Individuals with bulimia nervosa (BN) often report co-morbid symptoms of non
      suicidal self-injury (NSSI). This study examined the influence of (lack of)
      perseverance, (lack of) premeditation, sensation seeking, and negative urgency
      (the tendency to act rashly when experiencing negative affect) on these two
      behavior patterns. We hypothesized that negative urgency influences vulnerability
      to multiple maladaptive behavior patterns, thus influencing the co-occurrence of
      NSSI and BN symptoms. 489 young adult women completed baseline assessments, and
      209 completed an eight month follow-up assessment. Structural equation modeling
      was used to examine the influence of four personality pathways to impulsive
      behavior simultaneously on both behaviors at baseline, and the incremental
      predictive utility of traits on both behaviors at eight month follow up.
      Additionally, we examined the influence of NSSI at baseline on symptoms of BN at
      follow up, and symptoms of BN at baseline on NSSI at follow up. Negative urgency
      accounted for significant variance in NSSI and eating pathology. Baseline (lack
      of) perseverance contributed significantly to binge eating frequency at follow
      up, when accounting for baseline symptoms. NSSI at baseline was associated with
      increased purging at follow-up. Individual differences in impulsivity appear to
      influence both NSSI and eating pathology.

PMID- 23121785
TI  - The impact of age and BMI on impairment due to disordered eating in a large
      female community sample.
AB  - The impact of age and BMI on functional impairment in eating disorders was
      assessed by the Clinical Impairment Assessment (CIA) scale in a representative
      community sample. The CIA was administered to 1080 women aged 16-50 years
      (M=36.2, SD=9.5) with a range of BMI from 13.5 to 55.0 (M=24.6, SD=4.9) randomly
      selected from the Norwegian National Population Register. The average global CIA
      score was 5.3 (SD=8.5). Impairment tended to decrease with age (r(s)=-.20,
      p<.01), yet increased with greater BMI (r(s)=.31, p<.01). Approximately 30% of
      the participants with obesity scored in the clinical range compared to 7% of the
      underweight and normal-weight participants. Data supported the utility and
      feasibility of the CIA as a measure of functional impairment secondary to weight,
      shape, and eating concerns. It is recommended that age and BMI be considered
      during the interpretation of CIA data.

PMID- 23121786
TI  - Disordered eating, perfectionism, and food rules.
AB  - Clinically significant trait perfectionism is often characteristic of individuals
      exhibiting symptoms of eating disorders. The present study reports on a measure
      developed to assess the use of food rules and evaluates the hypothesis that
      adherence to food rules may be one mechanism through which trait perfectionism
      exacerbates risk for developing eating disorder symptoms. Forty-eight female
      college students completed a battery of questionnaires, and multiple regression
      analyses were used to test a mediational model. Results indicated that adherence
      to food rules mediated the relationship between self-oriented perfectionism and
      three indices of disordered eating in this sample. This relationship was specific
      to self-oriented perfectionism and did not hold for other-oriented or socially
      prescribed perfectionism. These findings may have implications for designing
      early interventions for disordered eating and may be useful in tailoring
      treatment for individuals with disordered eating who also report high levels of
      perfectionism.

PMID- 23121787
TI  - Changes in weight control behaviors and hedonic hunger during a 12-week
      commercial weight loss program.
AB  - Greater use of key self-regulatory behaviors (e.g., self-monitoring of food
      intake and weight) is associated with greater weight loss within behavioral
      weight loss treatments, although this association is less established within
      widely-available commercial weight loss programs. Further, high hedonic hunger
      (i.e., susceptibility to environmental food cues) may present a barrier to
      successful behavior change and weight loss, although this has not yet been
      examined. Adult men and women (N=111, body mass index M+/-SD=31.5+/-2.7kg/m(2))
      were assessed before and after participating in a 12-week commercial weight loss
      program. From pre- to post-treatment, reported usage of weight control behaviors
      improved and hedonic hunger decreased, and these changes were inversely
      associated. A decrease in hedonic hunger was associated with better weight loss.
      An improvement in reported weight control behaviors (e.g., self-regulatory
      behaviors) was associated with better weight loss, and this association was even
      stronger among individuals with high baseline hedonic hunger. Findings highlight
      the importance of specific self-regulatory behaviors within weight loss
      treatment, including a commercial weight loss program developed for widespread
      community implementation. Assessment of weight control behavioral skills usage
      and hedonic hunger may be useful to further identify mediators of weight loss
      within commercial weight loss programs. Future interventions might specifically
      target high hedonic hunger and prospectively examine changes in hedonic hunger
      during other types of weight loss treatment to inform its potential impact on
      sustained behavior change and weight control.

PMID- 23121788
TI  - Mediators between perfectionism and eating disorder psychopathology in a
      community sample.
AB  - The aim of this study was to investigate the mediating effect of shape and weight
      overvaluation and conditional goal-setting on the relationship between
      perfectionism and eating pathology among women in the general community. Results
      from structural equation modeling indicated that the full mediation model
      previously established with a clinical sample (Watson et al., 2011), generalized
      to the present community sample (n=202). The indirect effect of self-oriented
      perfectionism on eating disorder pathology was .25 (p<.001) via shape and weight
      overvaluation, and .10 (p<.01) via conditional goal-setting, supporting the
      hypothesis that self-oriented perfectionism increased eating disorder
      psychopathology via each mechanism. Shape and weight overvaluation was the
      stronger mediator. The findings provide evidence to support existing cognitive
      behavioral formulations of eating pathology and clinical perfectionism, and have
      implications for the prevention of eating pathology.

PMID- 23121789
TI  - The Food Craving Questionnaire-Trait in a bariatric surgery seeking population
      and ability to predict post-surgery weight loss at six months.
AB  - Food cravings have been understudied in bariatric surgery patients and the Food
      Craving Questionnaire-Trait has not been validated in this population.
      Reliability and validity of the FCQ-T were examined and a regression analysis was
      run to determine whether or not preoperative scores on individual subscales of
      the instrument could predict weight loss at 6 months. The FCQ-T demonstrated
      excellent internal consistency in bariatric surgery-seeking patients, and
      individual subscales measuring emotion and mood were correlated with other
      measures of depression and anxiety. Endorsement of binge eating or emotional
      eating behaviors during a clinical interview was correlated with similar
      subscales on the FCQ-T. Higher scores on the subscale 'cues that may trigger food
      cravings' were associated with greater weight loss at 6 months post-surgery and
      higher scores on the subscale 'guilt from cravings and/or giving into them' was
      associated with less weight loss. Management of external cues may predict
      successful outcomes while emotional impact of cravings may indicate the need for
      further intervention to help manage specific food craving traits.

PMID- 23121790
TI  - The relationship between eating-related individual differences and visual
      attention to foods high in added fat and sugar.
AB  - OBJECTIVE: Attentional biases for food-related stimuli may be associated
      separately with obesity, disordered eating, and hunger. We tested an integrative
      model that simultaneously examines the association of body mass index (BMI),
      disordered eating and hunger with food-related visual attention to processed
      foods that differ in added fat/sugar level (e.g., sweets, candies, fried foods)
      relative to minimally processed foods (e.g., fruits, meats/nuts, vegetables) that
      are lower in fat/sugar content. METHODS: One-hundred overweight or obese women,
      ages 18-50, completed a food-related visual search task and measures associated
      with eating behavior. Height and weight were measured. RESULTS: Higher levels of
      hunger significantly predicted increased vigilance for sweets and candy and
      increased vigilance for fried foods at a trend level. Elevated hunger was
      associated significantly with decreased dwell time on fried foods and, at a trend
      level, with decreased dwell time on sweets. Higher BMIs emerged as a significant
      predictor of decreased vigilance for fried foods, but BMI was not related to
      dwell time. Disordered eating was unrelated to vigilance for or dwell time on
      unhealthy food types. CONCLUSIONS: This pattern of findings suggests that low
      level attentional biases may contribute to difficulties making healthier food
      choices in the current food environment and may point toward useful strategies to
      reduce excess food consumption.

PMID- 23121791
TI  - Eating self-efficacy: development of a short-form WEL.
AB  - Self-efficacy for eating is an important predictor of the successful adoption and
      maintenance of weight management behaviors. The Weight Efficacy Lifestyle
      Questionnaire (WEL) is a commonly used measure of eating self-efficacy consisting
      of 20-items and five situational factors. The aim of this study was to develop a
      short-form WEL (WEL-SF) for use in clinical practice and research. Factor
      analysis methodology was used with a sample of obese patients (N=1012) seeking
      weight loss treatment to develop the WEL-SF. The hypothesis was that the WEL
      would contain highly correlated items within the factors, and consequently could
      be shortened with minimal loss of clinically important information. Results
      revealed a one-factor solution. Given this unexpected finding, factor analysis
      was abandoned and alternative selection criteria were implemented. WEL-SF items
      were selected based upon: (1) lack of a ceiling effect for individual items, (2)
      high variability in patient responses, (3) lack of a strong correlation with
      other WEL items, (4) strong correlation with total WEL score, and (5) clinical
      judgment regarding importance and interpretability of individual items. These
      criteria resulted in an 8-item measure. The correlation between the WEL-SF total
      score and WEL total score was extremely strong, with a Pearson's r value of 0.968
      and corresponding r(2) value of 0.937. Based on these findings, the 8-item WEL-SF
      appears to be a psychometrically valid measure of eating self-efficacy that
      accounts for 94% of the variability in the original version.

PMID- 23121792
TI  - Confirmatory factor analysis for the Eating Disorder Examination Questionnaire:
      Evidence supporting a three-factor model.
AB  - OBJECTIVE: The purpose of this investigation was to compare the goodness-of-fit
      of a one factor model with the four factor model proposed by Fairburn (2008) and
      the three factor model proposed by Peterson and colleagues (2007) for the Eating
      Disorder Examination Questionnaire (EDE-Q 6.0) (Fairburn and Beglin, 1994).
      METHOD: Using a cross-sectional design, the EDE-Q was completed by 569 adults
      recruited from universities and eating disorder charities in the UK. Confirmatory
      factor analysis (CFA) was carried out for both the student and non-student
      groups. RESULTS: CFA indicated that Peterson et al.'s (2007) three factor model
      was the best fit for both groups within the current data sample. Acceptable
      levels of internal reliability were observed and there was clear evidence for a
      hierarchical factor of eating disorder. DISCUSSION: The results of this study
      provide support for the three factor model of the EDE-Q suggested by Peterson and
      colleagues (2007) in that this model was appropriate for both the student and non
      student sample populations.

PMID- 23121793
TI  - The role of emotional dysregulation in concurrent eating disorders and substance
      use disorders.
AB  - This study explored the role of emotional dysregulation in 178 participants with
      concurrent EDs and SUDs. We ran two path analyses: Model 1 predicted negative
      mood regulation from alexithymia, and Model 2 predicted emotional eating from
      negative mood regulation. For Model 1, difficulty identifying and describing
      feelings was related to poor coping expectancies, while externally-oriented
      thinking was related to greater coping expectancies. For Model 2, poor coping
      expectancies in general were related to emotional eating, while greater coping
      expectancies in relation to behavior (i.e., the belief that some behavior or
      action can alleviate one's negative affect) also resulted in increased emotional
      eating. This finding suggests that there may be differences in the purpose of
      emotional eating; some people may believe that emotional eating can be used as an
      effective coping strategy to deal with negative affect.

PMID- 23121794
TI  - Body checking and avoidance in women: associations with mental and physical
      health-related quality of life.
AB  - Body checking and body avoidance have demonstrated clinical significance in a
      number of populations. However, the associations between these behaviors and
      mental and physical health-related quality of life have not been examined. This
      study investigated the associations between body checking and avoidance and
      quality of life in 214 community women. Body checking and body avoidance were
      significantly correlated with mental and physical quality of life, as well as
      with eating disturbances. Frequency of body checking significantly predicted
      impairment in mental quality of life, and frequency of body avoidance
      significantly predicted impairment in physical quality of life, over and above
      the contributions of depressive symptoms and related demographic characteristics.
      Targeting checking and avoidance in prevention and treatment programs may improve
      quality of life and reduce health-related functional impairment.

PMID- 23121795
TI  - Unique relationships between facets of mindfulness and eating pathology among
      female smokers.
AB  - Female smokers often have higher levels of eating disorder symptoms than non
      smokers, and concerns about eating and weight might interfere with smoking
      cessation. Thus, it is critical to identify factors to promote healthier eating
      and body image in this population. Initial research suggests that specific
      aspects of trait mindfulness predict lower body dissatisfaction and eating
      disorder symptoms among non-smokers. However, these relationships are unknown
      among smokers. The current study examined associations between facets of trait
      mindfulness and eating disorder symptoms in 112 college female smokers (83%
      Caucasian; mean age 20 years, SD=1.69). After controlling for relevant
      sociodemographic variables, Describing and Nonjudging facets of mindfulness
      predicted lower bulimic symptoms and body dissatisfaction (ps<.05), while Acting
      with Awareness predicted lower bulimic and anorexic symptoms, ps<.05. Observing
      predicted higher anorexic symptoms, p<.05. These results suggest that specific
      mindfulness facets are related to lower eating disorder symptoms among smokers,
      whereas other facets are not associated or have a positive relationship with
      these symptoms. Mindfulness-based interventions focusing on Describing,
      Nonjudging, and Acting with Awareness may help to reduce eating pathology among
      female smokers, which could potentially improve smoking cessation rates in this
      population.

PMID- 23121796
TI  - Psychological characteristics and associations with weight outcomes two years
      after gastric bypass surgery: Postoperative eating disorder symptoms are
      associated with weight loss outcomes.
AB  - This study investigated symptoms of eating disorder, depression, and anxiety
      among Roux-en-Y gastric bypass patients two years after surgery, and the
      relationship between these characteristics and weight loss. Respondents completed
      assessment questionnaires including Eating Disorder Inventory-2 (EDI-2), Harvard
      Anxiety and Depression Scale (HADS), and questions related specifically to binge
      eating. Forty-five patients (8 men, 37 women) out of 65 (67%) responded. Scores
      were significant higher on impulse regulation, interoceptive awareness,
      ineffectiveness, maturity fears and interpersonal distrust in comparison with a
      Danish norm group (p<=0.05). The weight losses obtained after surgery varied from
      12 to 60% of the starting weights. Binge eating and ineffectiveness were found to
      significantly correlate with weight loss variations after surgery (p<=0.05). The
      results of this study indicate that knowledge of the potential influence of
      eating disorder symptoms on outcomes after bariatric surgery is needed in order
      to optimize weight outcomes following surgery.

PMID- 23121797
TI  - Does the Internet function like magazines? An exploration of image-focused media,
      eating pathology, and body dissatisfaction.
AB  - Research has identified a relation between exposure to thin-ideal magazine and
      television media images and eating disorder pathology. However, few studies have
      examined the potential influence of Internet media on eating disorder behaviors
      and attitudes. This study investigated associations among image-focused media
      exposure, body dissatisfaction, eating pathology and thin-ideal internalization
      in a sample of 421 female undergraduates. Undergraduate women spent significantly
      more time viewing online appearance-oriented media, rather than reading image
      focused magazines. Appearance-oriented Internet and television use were
      associated with eating pathology. Moreover, the association between image-focused
      Internet use and BD was mediated by thin-ideal internalization. These findings
      are consistent with those of previous research, and highlight the vulnerability
      individuals high in thin-ideal internalization might have to media exposure. They
      also suggest that Internet media use is an important topic to attend to in eating
      disorders prevention and treatment.

PMID- 23121798
TI  - A preliminary evaluation of BMI status in moderating changes in body composition
      and eating behavior in ethnically-diverse first-year college women.
AB  - The present pilot investigation explored whether BMI status at college entry
      moderated changes in body composition and eating behavior in a sample of 134
      first-time, first-year undergraduate females (40% Black/African American).
      Participants had their body measurements [i.e. weight, BMI, hip and waist
      circumference (WC), percent body fat (PBF)] assessed and completed self-report
      measures of binge eating, night eating, and intuitive eating at both the
      beginning of the fall and the beginning of the spring semesters of their first
      year. Results for the 83 completers revealed that overweight/obese students
      (N=28) experienced greater gains in weight (p<0.05), BMI (p<0.05), and a trend
      towards increased WCs (p<0.06) across the first college semester relative to
      their underweight/normal weight peers (N=55). Night eating increased (p<0.05) and
      intuitive eating declined (p<0.05) over time in the full sample. Overweight/obese
      participants indexed greater binge eating scores (p<0.001) and lower intuitive
      eating scores (p<0.01) irrespective of time. Most anthropometric findings were
      diminished while all eating behavior estimates were retained in subsequent models
      adjusted for parental income. Preliminary results call attention to the need for
      continued elucidation of the roles of socioeconomic and regional diversity in
      affecting both the prevalence of overweight/obesity and the relationship between
      higher weight and body composition changes among first-year college women.
      Findings also provide tentative behavioral targets for college wellness
      programming that may prove useful in promoting healthy weight management while
      acclimating to the college environment.

PMID- 23121799
TI  - Moderation: an alternative to restraint as a mode of weight self-regulation.
AB  - This study considered two types of eating and weight self-regulation, in five
      groups, including four types of weight controllers and one non-dieting group. New
      scales were developed to measure eating moderation and restraint. Moderation was
      largely uncorrelated with restraint in 4 groups and had a fairly strong positive
      relation in 1 group. The moderation scale was unrelated to the Dutch Eating
      Behavior Questionnaire (DEBQ) restraint scale and the Three Factor Eating
      Questionnaire (TFEQ) rigid restraint subscale and weakly positively related to
      TFEQ flexible restraint. The restraint scale was strongly correlated to the DEBQ
      restraint scale, and to both flexible and rigid restraint subscales of the TFEQ.
      Across the five groups, moderation had exclusively positive relationships with
      attitude, behavior and emotion variables, while restraint had primarily negative
      relationships. The study supports moderation as a new dimension of weight self
      regulation, independent of restraint. The new measures of moderation and
      restraint can be used together in research on the processes of change in weight
      management.

PMID- 23121800
TI  - Spanish-language Eating Disorder Examination interview: factor structure in
      Latino/as.
AB  - Latino/as face health care disparities in eating/weight disorders but are under
      represented in treatment research and this is especially the case for Spanish
      speaking-only persons. The development of psychometrically-sound assessment
      methods for Latino/as is needed to facilitate eating/weight research. The current
      study aimed to evaluate the factor structure of the Spanish-language version of
      the Eating Disorder Examination (S-EDE) interview, one of the primary assessment
      methods in studies of eating/weight despite limited data regarding psychometric
      aspects of this measure. Participants were 156 Spanish-speaking-only Latino/as
      (mean BMI 33.2; 84.6% classified as overweight) who were reliably administered
      the S-EDE interview by trained bi-lingual doctoral research-clinicians.
      Confirmatory factor analysis revealed an inadequate fit for the original EDE
      structure but revealed a good fit for an alternative structure suggested by
      recent research. CFA supported an 8-item 3-factor structure; the three factors
      were interpreted as dietary restraint, shape/weight overvaluation, and body
      dissatisfaction. These factor analytic findings of the Spanish EDE interview are
      comparable to recent findings reported for English-speaking obese patient groups
      and have implications for clinical assessment and research with Latino/as.

PMID- 23121801
TI  - State and trait food craving in people with bulimic eating disorders.
AB  - In two studies, we examined trait and state food craving levels in people with a
      bulimic disorder (BD) (bulimia nervosa and related disorders) and healthy
      controls (HC) using multidimensional self-report assessments. In study 1, trait
      food craving was assessed in 70 people with a BD and 69 HC using the Food Craving
      Questionnaire-Trait. Participants also completed the Eating Disorder Examination
      Questionnaire (EDE-Q). In study 2, 45 people with a BD and 29 HC completed the
      Food Craving Questionnaire-State and the EDE-Q following exposure to visual and
      real high-caloric food cues. The results showed that both trait and state food
      cravings were significantly higher in people with a BD, compared to HC. Trait
      food craving was associated with eating disorder symptomatology in both the HC
      and BD groups. State food craving was associated with eating disorder
      psychopathology, but only in the BD group. This research underscores the
      importance of food craving in the study and conceptualization of BD.

PMID- 23121802
TI  - Evaluating the roles of anxiety and dimensions of perfectionism in dieting and
      binge eating using weekly diary methodology.
AB  - This study examined the relations between weekly reports of anxiety, dimensions
      of trait perfectionism, and dieting and binge eating over the course of 11 weeks.
      Participants were 406 college women who completed a battery of questionnaires at
      Time 1 that assessed trait-like characteristics (e.g., self-oriented and socially
      prescribed perfectionism). For 11 weeks following that, participants filled out a
      short questionnaire packet that assessed their weekly anxiety, dieting, and binge
      eating. Using multilevel modeling, results indicated that on average, both within
      and between-person levels of anxiety predicted increased binge eating, while
      only between-person levels of anxiety predicted increased dieting. Higher levels
      of self-oriented perfectionism also predicted increased dieting and binge eating,
      while higher levels of socially prescribed perfectionism predicted increased
      binge eating only (not increased dieting). The relation between weekly anxiety
      and disordered eating was not moderated by either dimension of perfectionism.
      Results provide support for the notion that dieting is generally affected by
      trait-like characteristics, while binge eating is generally affected by both
      trait- and state-like characteristics; these findings have significant clinical
      implications.

PMID- 23121803
TI  - Women with elevated food addiction symptoms show accelerated reactions, but no
      impaired inhibitory control, in response to pictures of high-calorie food-cues.
AB  - Addictive behaviors are accompanied by a lack of inhibitory control, specifically
      when individuals are confronted with substance-related cues. Thus, we expected
      women with symptoms of food addiction to be impaired in inhibitory control, when
      confronted with palatable, high-calorie food-cues. Female college students (N=50)
      were divided in low and high food addiction groups based on the symptom count of
      the Yale Food Addiction Scale. Participants performed a Go/No-go-task with high
      calorie food-cues or neutral pictures presented behind the targets. Self-reported
      impulsivity was also assessed. The high food addiction group had faster reaction
      times in response to food-cues as compared to neutral cues and reported higher
      attentional impulsivity than the low food addiction group. Commission and
      omission errors did not differ between groups or picture types. Hence, women with
      food addiction symptoms reported higher attentional impulsivity and reacted
      faster in response to food-cues, although neither increased self-reported motor
      impulsivity nor impaired behavioral inhibition was found. Food addiction symptoms
      seem to be related to attentional aspects of impulsivity but not other facets of
      impulsivity.

PMID- 23121804
TI  - Eating Disorder Examination Questionnaire (EDE-Q): norms for Black women.
AB  - The current study provides Eating Disorder Examination Questionnaire (EDE-Q)
      norms for Black undergraduate women (N=395). EDE-Q subscale scores, clinical
      cutoffs, and disordered eating behavior were compared with previously published
      norms for primarily White undergraduate and community samples. The current sample
      endorsed mean EDE-Q scores similar to those of White females recruited from the
      community. Regarding clinical cutoffs, Black women in the current sample were
      most similar to White college women. Despite similar EDE-Q scores, the current
      sample endorsed significantly less binge eating and compensatory behaviors than
      White undergraduate or community women. Outcomes suggest that increased eating-
      and weight-related concerns among Black undergraduate women might not be
      associated with disordered eating behavior. Similarly, results suggest that the
      validity of EDE-Q cutoffs is lower in samples of Black women compared with
      samples of White women. Additional research is needed to enhance understanding of
      eating disorder risk factors for Black college women.

PMID- 23121805
TI  - [Congenital cervical salivary fistula: a case report].
AB  - Cyst and fistulas of the gills grooves and thyro-glossal tracts are well
      documented. On the contrary, congenital neck salivary fistulas are uncommon.

PMID- 23121807
TI  - Catching up with evidence-based medicine.

PMID- 23121806
TI  - Gateway vectors for transformation of cereals.
AB  - Until now, the availability of vectors for transgenic research in cereal crops
      has been rather limited. We present a novel collection of Agrobacterium
      tumefaciens binary T-DNA vectors compatible with Gateway recombinational cloning
      that facilitate the modular assembly of genes of interest together with new
      regulatory sequences, such as strong constitutive or endosperm-specific
      Brachypodium distachyon promoters. This resource aims at streamlining the
      creation of vectors and transgenes designed to explore gene functions in vital
      monocotyledonous crops.

PMID- 23121808
TI  - When the evidence isn't there--seeking informed consent for new procedures.

PMID- 23121809
TI  - The debate over prostate cancer screening guidelines.

PMID- 23121810
TI  - Responding to patient requests for nonindicated care.

PMID- 23121811
TI  - Insights from teaching evidence-based medicine.

PMID- 23121812
TI  - The AMA Code of Medical Ethics' opinion on physician pay-for-performance
      programs.

PMID- 23121814
TI  - Health effects of smoking and the benefits of quitting.

PMID- 23121813
TI  - The limitations of evidence-based medicine--applying population-based
      recommendations to individual patients.

PMID- 23121815
TI  - The role of practice guidelines in medical malpractice litigation.

PMID- 23121816
TI  - The role of comparative effectiveness research in developing clinical guidelines
      and reimbursement policies.

PMID- 23121817
TI  - Rating evidence in medical literature.

PMID- 23121818
TI  - Is there room for art in evidence-based medicine?

PMID- 23121820
TI  - Physical examination prior to initiating hormonal contraception: a systematic
      review.
AB  - BACKGROUND: Provision of contraception is often linked with physical examination,
      including clinical breast examination (CBE) and pelvic examination. This review
      was conducted to evaluate the evidence regarding outcomes among women with and
      without physical examination prior to initiating hormonal contraceptives. STUDY
      DESIGN: The PubMed database was searched from database inception through March
      2012 for all peer-reviewed articles in any language concerning CBE and pelvic
      examination prior to initiating hormonal contraceptives. The quality of each
      study was assessed using the United States Preventive Services Task Force grading
      system. RESULTS: The search did not identify any evidence regarding outcomes
      among women screened versus not screened with CBE prior to initiation of hormonal
      contraceptives. The search identified two case-control studies of fair quality
      which compared women who did or did not undergo pelvic examination prior to
      initiating oral contraceptives (OCs) or depot medroxyprogesterone acetate (DMPA).
      No differences in risk factors for cervical neoplasia, incidence of sexually
      transmitted infections, incidence of abnormal Pap smears or incidence of abnormal
      wet mount findings were observed. CONCLUSIONS: Although women with breast cancer
      should not use hormonal contraceptives, there is little utility in screening
      prior to initiation, due to the low incidence of breast cancer and uncertain
      value of CBE among women of reproductive age. Two fair quality studies
      demonstrated no differences between women who did or did not undergo pelvic
      examination prior to initiating OCs or DMPA with respect to risk factors or
      clinical outcomes. In addition, pelvic examination is not likely to detect any
      conditions for which hormonal contraceptives would be unsafe.

PMID- 23121821
TI  - Contraception access and use among U.S. servicewomen during deployment.
AB  - BACKGROUND: Approximately 12% of active duty US servicewomen have an unintended
      pregnancy each year; however, little is known about contraception use during
      deployment. STUDY DESIGN: From April to November 2010, we conducted an online
      survey with a convenience sample of 281 servicewomen who had been deployed
      overseas to assess access to and use of contraception for deployment. RESULTS:
      Sixty-three percent of respondents used birth control for part or all of their
      last deployment. Although military health insurance covers most contraceptive
      methods, one third reported that they were unable to access a method they might
      want for deployment, and 59% did not speak with a military provider about
      contraceptive options prior to deployment. Certain methods were reportedly
      discouraged or not available for some women, including intrauterine devices and
      sterilization, and 41% of women requiring refills found them difficult to obtain.
      CONCLUSIONS: Given the high prevalence of unintended pregnancy among
      servicewomen, efforts should focus on improving contraceptive counseling prior to
      deployment and ensuring refill access during deployment, as well as expanding
      access to long-acting reversible methods.

PMID- 23121822
TI  - Mood and physical symptoms improve in women with severe cyclical changes by
      taking an oral contraceptive containing 250-mcg norgestimate and 35-mcg ethinyl
      estradiol.
AB  - BACKGROUND: The purpose of this study was to investigate how women without and
      with different severity of premenstrual symptoms react to treatment with a
      combined oral contraceptive containing 250-mcg norgestimate/35-mcg ethinyl
      estradiol (EE). Focus was placed on mood and physical symptoms. STUDY DESIGN:
      This open, prospective study evaluated 24 women using norgestimate/EE for three
      cycles in a 21/7 regimen. Symptoms and bleeding pattern were captured by daily
      ratings on the Cyclicity Diagnoser scale. RESULTS: Women with severe premenstrual
      mood symptoms improved in summarized negative mood (p<.001) and summarized
      positive mood (p<.05), as well as in swelling (p<.05) and effect on daily life
      (p<.05). Women with no or mild or moderate symptoms did not show any significant
      improvement or deterioration in any symptom after 3 months of treatment.
      CONCLUSIONS: Norgestimate 250 mcg/EE 35 mcg significantly improved premenstrual
      summarized negative mood symptoms during 3 treatment months compared to
      pretreatment in women with severe premenstrual symptoms, together with
      improvement in positive symptoms, swelling and effect on daily life.

PMID- 23121823
TI  - The use of dual or two methods for pregnancy and HIV prevention amongst 18-24
      year-olds in a cross-sectional study conducted in South Africa.
AB  - INTRODUCTION: The use of dual (for pregnancy and disease prevention) or two
      methods of contraceptives is recommended for the prevention of unwanted
      pregnancies and protection against sexually transmitted diseases such as HIV. The
      study aims to assess the prevalence and explore factors associated with the use
      of dual or two methods among young people aged 18 to 24 years in South Africa.
      METHODS: Factors associated with use of dual or two methods among young people
      aged 18 to 24 years in South Africa were investigated by individual interviews.
      The final sample included 1127 males and 1007 females from four provinces
      (Eastern Cape, Gauteng, KwaZulu-Natal and Mpumalanga) who reported to have ever
      had sex. RESULTS: The study found among men (18-24 years) 10.4% and among women
      (18-24 years) 15.4%, current use of dual or two methods was reported. In
      multivariate analyses, among women, lower poverty, not being unemployed, having
      concurrent sexual partners and higher sexual intercourse frequency in the past
      month were associated with use of dual or two methods, while for men,
      contraceptive methods knowledge, greater relationship control and higher sexual
      intercourse frequency in the past month were associated with use of dual or two
      methods. CONCLUSION: The use of dual or two methods remains low. Innovative ways
      are needed for the promotion and increased use of dual or two methods.

PMID- 23121824
TI  - The LIF receptor antagonist PEGLA is effectively delivered to the uterine
      endometrium and blocks LIF activity in cynomolgus monkeys.
AB  - BACKGROUND: Leukemia inhibitory factor (LIF) is a cytokine with an essential role
      in the preparation of the endometrium for implantation. Previous studies
      demonstrated that PEGLA, a LIF receptor antagonist (LA) conjugated with
      polyethylene glycol (PEG), effectively prevents implantation in mice, identifying
      PEGLA as a potential contraceptive for women. STUDY DESIGN: Adult female
      cynomolgus macaques were used to determine the optimal route of administration to
      deliver PEGLA to the uterine endometrium. Endometrial explants were used to
      examine the ability of PEGLA to block LIF action at endometrial cells. RESULTS:
      Both intramuscular and subcutaneous PEGLA administration resulted in peak serum
      PEGLA 24 h after administration; serum PEGLA was detectable throughout the 144-h
      sampling period. In contrast, serum PEGLA was near or below the limit of
      detection after vaginal administration. After intramuscular administration, PEGLA
      was localized to both luminal and glandular epithelial cells of the uterine
      endometrium, and PEGLA was measurable in endometrial lysates. PEGLA
      administration reduced endometrial signal transducer and activator of
      transcription protein 3 (STAT3) phosphorylation in vivo and in vitro. PEGLA also
      blocked LIF's ability to elevate expression of cochlin, insulin-like growth
      factor-binding protein 3, vascular endothelial growth factor A, and
      cyclooxygenase-2 (also known as PTGS2) in endometrial explants in vitro.
      CONCLUSIONS: PEGLA was delivered to the non-human primate uterine endometrium
      with systemic administration, and PEGLA blocked LIF actions associated with
      implantation. Blocking LIF receptor activity with the antagonist PEGLA may
      prevent pregnancy in women and provide a novel alternative to currently-available
      hormonal and barrier contraceptives.

PMID- 23121825
TI  - Women's information-seeking behavior after receiving contraceptive versus
      noncontraceptive prescriptions.
AB  - BACKGROUND: Contraceptives are among the most commonly prescribed medications
      used by women of reproductive age, but little is known about women's information
      seeking behavior after receiving prescriptions for medication. STUDY DESIGN: All
      reproductive-age women who visited one of four primary care clinics in Western
      Pennsylvania between October 2008 and April 2010 were invited to complete a
      follow-up survey after their visit which included questions regarding medications
      prescribed, information-seeking after their visit and their perceptions of the
      quality of the information they found. RESULTS: Of the 218 women prescribed
      contraceptives, 49% sought additional information after their visit. In models
      adjusted for sociodemographic and reproductive characteristics of the
      respondents, women who received a contraceptive prescription were twice as likely
      to seek additional information about their medication as women who received
      noncontraceptive prescriptions [odds ratio (OR)=2.06, 95% confidence interval
      (CI) 1.47-2.90]. Women who received a contraceptive prescription were more likely
      to seek information from the Internet (OR=1.84, 95% CI 1.26-2.70) and from the
      package insert (OR=1.55, 95% CI 1.02-2.36) than women who received
      noncontraceptive prescriptions. CONCLUSIONS: Women frequently sought additional
      information on contraceptive prescriptions. Efforts are needed to increase the
      quantity and improve the quality of contraceptive counseling provided by primary
      care providers and the quality of the information provided by package inserts and
      the Internet.

PMID- 23121827
TI  - Prevention and management of nausea and vomiting with emergency contraception: a
      systematic review.
AB  - BACKGROUND: Nausea and vomiting are side effects of emergency contraception pill
      (ECP) use. Different ECP regimens and the use of antinausea drugs may prevent
      these side effects. METHODS: We conducted two searches to identify data
      pertaining to the prevention of nausea and vomiting with ECP use and management
      of emesis with ECP use. Both searches queried the PubMed and Cochrane databases
      for peer-reviewed articles, in any language, published on January 1966-February
      2012. Types of ECP included in our searches were levonorgestrel (LNG), Yuzpe
      regimens or ulipristal acetate (UA). Our search strategy for data on management
      of emesis with ECP use also included the gray literature. The gray literature
      includes materials such as reports, patent claims, prescribing information and
      package labels that are not published commercially. RESULTS: Eleven articles met
      the inclusion criteria. Split dose or two doses of LNG caused less nausea than UA
      and standard two-dose Yuzpe regimen in one study. Four studies demonstrated no
      difference between split-dose versus single-dose LNG. In two trials, meclizine
      and metoclopramide, given before Yuzpe ECPs, reduced nausea, but only meclizine
      reduced vomiting. CONCLUSION: The evidence does not support routine use of
      antiemetics with ECP use. Data to guide management of emesis with ECP are limited
      to expert opinion and package labeling.

PMID- 23121826
TI  - Optimal methods for collecting and storing vaginal specimens for prostate
      specific antigen testing in research studies.
AB  - BACKGROUND: Prostate-specific antigen (PSA) detected in vaginal fluid can be used
      in studies of HIV/sexually transmitted infection (STI) and pregnancy prevention
      as an alternative to relying on participant reports of exposure to semen. Optimal
      methods for collecting and storing specimens for this testing have not been
      determined. STUDY DESIGN: We conducted a controlled, in vitro experiment of 550
      specimens spiked with semen to determine the effects of swab type (five types),
      storage conditions of the swabs (room temperature with or without desiccant or at
      -80 degrees C without desiccant) and time from collection to testing (seven
      intervals over the course of 12 months) on the identification of PSA. We
      performed factorial analysis of variance to identify factors influencing PSA
      detection. RESULTS: Concentrations of PSA detected in the swabs declined with
      time of storage over the 1-year experiment (p<.01). The 1-mL, rayon-tipped swab
      stored immediately at -80 degrees C following collection performed best.
      CONCLUSIONS: If immediate testing or freezer storage is not feasible,
      investigators should use a swab with 1-mL capacity with processing and testing as
      soon as possible after specimen collection.

PMID- 23121828
TI  - Temporal changes in cervical mucus after insertion of the levonorgestrel
      releasing intrauterine system.
AB  - BACKGROUND: The major contraceptive action of the levonorgestrel-releasing
      intrauterine system (LNG-IUS) is cervical mucus (CM) thickening, which prevents
      sperm penetration. No study to date has examined the temporal relationship
      between the insertion of the LNG-IUS and changes in CM quality and sperm
      penetration. STUDY DESIGN: Participants were enrolled in a clinically descriptive
      study to compare the quality of CM and three parameters of sperm penetration
      prior to insertion of the LNG-IUS and on Days 1, 3 and 5 after insertion.
      Measurements of estradiol, progesterone and levonorgestrel (LNG) in serum and LNG
      in CM were also carried out at these times. CM was analyzed using the World
      Health Organization CM grading criteria. Sperm penetration was determined using
      an in vitro sperm-CM penetration test. RESULTS: All 10 participants underwent LNG
      IUS insertion during midcycle when CM quality was good and sperm penetration was
      excellent. On Day 1 after LNG-IUS insertion, the majority of participants
      demonstrated poor CM quality and poor sperm penetration. On Day 3, all
      participants had poor CM quality, and all but one subject had poor sperm
      penetration. By Day 5, all participants had poor CM quality and poor sperm
      penetration. LNG levels in CM peaked on the day after LNG-IUS insertion.
      CONCLUSION: Significant changes in quality of CM and sperm penetration were
      observed shortly after LNG-IUS insertion; however, CM can remain penetrable for
      up to 5 days when the LNG-IUS is inserted midcycle.

PMID- 23121829
TI  - Low-dose mifepristone increases uterine expression of aquaporin 1/aquaporin 2 at
      the time of implantation.
AB  - BACKGROUND: The aim of this study was to investigate the mechanism by which low
      dose mifepristone serves as an antiimplantation contraceptive drug. A human
      endometrial explant system was used to study the effects of low-dose mifepristone
      (65 nmol/L and 200 nmol/L) on expression of the water channel family aquaporins,
      aquaporin-1 and aquaporin-2 (AQP1/AQP2), at the time of implantation. STUDY
      DESIGN: Endometrial samples from 17 normally cycling patients at the "window of
      implantation" were treated with different concentrations of mifepristone. The
      protein and mRNA expression of AQP1/AQP2 in the endometrium was examined using
      immunohistochemistry (IHC) and reverse transcriptase-polymerase chain reaction
      (RT-PCR), respectively. RESULTS: The IHC and RT-PCR analyses demonstrated that
      expression of AQP1/AQP2 was increased by mifepristone in a dose-dependent manner,
      with the highest AQP1/AQP2 expression levels detected in subjects treated with
      200-nmol/L mifepristone. CONCLUSION: Low-dose mifepristone may negatively
      regulate implantation by increasing AQP1/AQP2 protein and mRNA expression. The
      findings from this study provide further evidence to support the potential
      contraceptive activity of low-dose mifepristone.

PMID- 23121830
TI  - The state of palliative care and heart failure.

PMID- 23121831
TI  - HFSA and AAHFN joint position statement: advocating for a full scope of nursing
      practice and leadership in heart failure.

PMID- 23121832
TI  - Patient- and family-centered care.

PMID- 23121833
TI  - The importance of antimicrobial peptides and their potential for therapeutic use
      in ophthalmology.
AB  - The reduced effectiveness of some of the most important antibiotics owing to
      increasing resistance of microorganisms as well as the absence of new classes of
      antimicrobial agents have been concerning researchers and clinicians in recent
      years. Thus, the development and approval of new compounds for clinical
      applications is of great importance. Among these compounds, antimicrobial
      peptides (AMPs) appear to be excellent candidates for the development of novel
      antimicrobial agents. Some AMPs and antimicrobial proteins have been shown to be
      active against relevant pathogens in ocular infections as well as in biofilm
      eradication from contact lenses. Thus, they are considered promising in the
      prevention and management of ocular diseases. This review summarises the main
      classes and characteristics of AMPs and antimicrobial proteins, in particular
      those found in ocular structures and fluids. Some AMPs with activity against
      ocular pathogens and their potential as therapeutic agents to treat and prevent
      ocular infections are emphasised.

PMID- 23121834
TI  - Human cytosolic glutathione transferases: structure, function, and drug
      discovery.
AB  - Glutathione transferases (GSTs) are important detoxifying enzymes that catalyze
      the conjugation of electrophilic substrates to glutathione. In recent years, GSTs
      have been of great interest in pharmacology and drug development because of their
      involvement in many important biological processes such as steroid and
      prostaglandin biosynthesis, tyrosine catabolism, and cell apoptosis. This review
      describes crystal structures for cytosolic GSTs and correlates active-site
      features with enzyme functions (e.g., steroid synthesis, tyrosine degradation,
      and dehydroascorbate reduction) and substrate selectivity. Use of these crystal
      structures for the design of specific inhibitors for several GST enzymes is also
      discussed.

PMID- 23121835
TI  - High resolution STEM of quantum dots and quantum wires.
AB  - This article reviews the application of high resolution scanning transmission
      electron microscopy (STEM) to semiconductor quantum dots (QDs) and quantum wires
      (QWRs). Different imaging and analytical techniques in STEM are introduced and
      key examples of their application to QDs and QWRs are presented. In addition, the
      benefits offered by aberration correction are discussed and an outlook for future
      developments of high resolution STEM analysis of QDs and QWRs is given.

PMID- 23121836
TI  - Rapid identification of a major diffusion/perfusion mismatch in distal internal
      carotid artery or middle cerebral artery ischemic stroke.
AB  - BACKGROUND: We tested the hypothesis that in patients with occlusion of the
      terminal internal carotid artery and/or the proximal middle cerebral artery, a
      diffusion abnormality of 70 ml or less is accompanied by a diffusion/perfusion
      mismatch of at least 100%. METHODS: Sixty-eight consecutive patients with
      terminal ICA and/or proximal MCA occlusions and who underwent diffusion/perfusion
      MRI within 24 hours of stroke onset were retrospectively identified. DWI and mean
      transit time (MTT) volumes were measured. Prospectively, 48 consecutive patients
      were identified with the same inclusion criteria. DWI and time to peak (TTP)
      lesion volumes were measured. A large mismatch volume was defined as an MTT or
      TTP abnormality at least twice the DWI lesion volume. RESULTS: In the
      retrospective study, 49 of 68 patients had a DWI lesion volume <= 70 ml (mean
      20.2 ml; SEM 2.9 ml). A DWI/MTT mismatch of > 100% was observed in all 49
      patients (P < .0001). In the prospective study, there were 35/48 patients with
      DWI volumes <= 70 ml (mean 18.7 ml; SEM 3.0 ml). A mismatch > 100% was present in
      all 35 (P < .0001). CONCLUSIONS: Acute stroke patients with major anterior
      circulation artery occlusion are exceedingly likely to have a major
      diffusion/perfusion mismatch if the diffusion lesion volume is 70 ml or less.
      This suggests that physiology-based patient assessments may be made using only
      vessel imaging and diffusion MRI as a simple alternative to perfusion imaging.

PMID- 23121837
TI  - One-year clinical prediction in Chinese ischemic stroke patients using the CHADS2
      and CHA2DS2-VASc scores: the China National Stroke Registry.
AB  - AIMS: We investigated whether CHADS2 or CHA2DS2-VASc scores could be used to
      predict 1-year prognosis in stroke recurrence, mortality, and mortality of
      ischemic stroke or transient ischemic attack (TIA) patients with nonvalvular
      atrial fibrillation (NVAF). METHODS: Patients were selected from a national
      prospective registry in China. The clinical prediction of the scores was examined
      using the C statistic. Univariate and multivariate logistic regressions were
      performed to analyze the relevant risk factors. RESULTS: Thousand two hundred and
      ninety-seven of 22,216 patients were enrolled in the study. For stroke recurrence
      rate, the C statistic value was 0.53 (odds ratio [OR] 1.15, 95% confidence
      interval [CI]: 1.01 to 1.32) for CHADS2 and 0.55 (OR 1.14, 95% CI: 1.05 to 1.24)
      for CHA2DS2-VASc; adding baseline National Institutes of Health Stroke Scale
      (NIHSS) score to these two scores, the value of C statistic was 0.58 (OR 1.25 95%
      CI: 1.14 to 1.37) and 0.58 (OR 1.19, 95% CI: 1.11 to 1.27), respectively.
      CONCLUSIONS: Both CHADS2 and CHA2DS2-VASc scores have limitations in predicting
      the 1-year prognosis of stroke/TIA patients with NVAF in China. The predictive
      value of these two scores improved by adding the baseline NIHSS score.

PMID- 23121838
TI  - Silymarin inhibits cell cycle progression and mTOR activity in activated human T
      cells: therapeutic implications for autoimmune diseases.
AB  - Silymarin, a complex flavonolignan from the 'milk thistle' (Silybum marianum)
      plant, exhibits anticarcinogenic, anti-inflammatory and cytoprotective effects.
      Several reports have demonstrated immunosuppressive activity of silymarin;
      however, the molecular mechanisms involved in immunomodulatory activities of
      silymarin are not fully understood yet. In this study, the effect of silymarin on
      cell cycle and PI3K/Akt/mTOR signalling pathway of activated T lymphocytes was
      investigated in vitro. Peripheral blood mononuclear cells (PBMC) were isolated
      from healthy volunteers and activated with anti-CD3 (5 MUg/ml) and anti-CD28 (2
      MUg/ml) monoclonal antibodies. Cells were cultured in Complete RPMI medium with
      10, 50 and 100 MUM silymarin or dimethyl sulphoxide (DMSO) and incubated for 24
      96 hrs. Cell cycle analysis was performed by PI staining and flow cytometry. The
      effect of silymarin on PI3K/AKT signalling pathway and mTOR activity was
      determined in activated T cells after 72-hr incubation with silymarin or DMSO. A
      significant G1 arrest in cell cycle of activated T lymphocytes was found after 96
      hr incubation with 100 MUM silymarin without causing cell death. Silymarin also
      significantly inhibited the level of phospho-S6 ribosomal protein and mTOR
      activity in cell lysates of activated T cells after 72-hr incubation in
      comparison with DMSO. This study shows that silymarin inhibits cell proliferation
      through G1 cell cycle arrest and also through the suppression of the mTOR
      signalling pathway in human activated T lymphocytes in vitro. Characterizing
      molecular mechanism of such immunomodulatory effects may have a great potential
      in future practical application of silymarin in transplantation and auoimmunity.

PMID- 23121840
TI  - Blastocyst biopsy and preimplantation genetic diagnosis for single gene diseases:
      a turnaround on the horizon?

PMID- 23121839
TI  - Human papillomavirus (HPV) genotype 18 variants in patients with clinical
      manifestations of HPV related infections in Bilbao, Spain.
AB  - BACKGROUND: Human papillomavirus (HPV) variants differ in their biological and
      chemical properties, and therefore, may present differences in pathogenicity.
      Most authors classified variants based on the phylogenetic analysis of L1 region.
      Nevertheless, recombination in HPV samples is becoming a usual finding and thus,
      characterizing genetic variability in other regions should be essential.
      OBJECTIVES: We aimed to characterize the genetic variability of HPV 18 in 5
      genomic regions: E6, E7, E4, L1 and the Upstream Regulatory Region (URR), working
      with both single infection and multiple HPV infection samples. Furthermore, we
      aimed to assess the prevalence of HPV 18 variants in our region and look for
      possible existence of recombination as well as analyze the relationship between
      these variants and the type of lesion. METHODS: From 2007 to 2010, Clinical
      Microbiology and Infection Control Department analyzed 44 samples which were
      positive for HPV 18. Genetic variability was determined in PCR products and
      variants were assigned to European, Asian-amerindian or African lineage.
      Recombination and association of variants with different types of lesion was
      studied. RESULTS: Genetic analysis of the regions revealed a total of 56
      nucleotide variations. European, African and Asian-amerindian variants were found
      in 25/44 (56.8%), 10/44 (22.7%) and 5/44 (11.4%) samples, respectively. We
      detected the presence of recombinant variants in 2/44 (4.5%) cases. Samples taken
      from high-grade squamous intraepithelial lesions (H-SIL) only presented variants
      with specific-african substitutions. CONCLUSIONS: Multiple HPV infection, non
      european HPV variants prevalence and existence of recombination are considered
      risk factors for HPV persistence and progression of intraepithelial
      abnormalities, and therefore, should be taken into consideration in order to help
      to design and optimize diagnostics protocols as well as improve epidemiologic
      studies.Our study is one of the few studies in Spain which analyses the genetic
      variability of HPV18 and we showed the importance of characterizing more than one
      genomic region in order to detect recombination and classify HPV variants
      properly.

PMID- 23121842
TI  - Waardenburg syndrome--a case report.
AB  - Waardenburg syndrome is a rare genetic disorder characterized by varying degree
      of deafness associated with pigmentary anomaly and defects of neural crest cell
      derived structures. Four subtypes (I-IV) with variable penetrance and gene
      expression of different clinical features have been described. We report a
      patient showing constellation of complete heterochromia, dystopia canthorum,
      white forelock, and synophrys. Other affected family relatives with heterochromia
      have been depicted in pedigree.

PMID- 23121841
TI  - Enhanced recovery after vascular surgery: protocol for a systematic review.
AB  - BACKGROUND: The enhanced recovery after surgery (ERAS) programme is a multimodal
      evidence-based approach to surgical care which begins in the preoperative setting
      and extends through to patient discharge in the postoperative period. The primary
      components of ERAS include the introduction of preoperative patient education;
      reduction in perioperative use of nasogastric tubes and drains; the use of
      multimodal analgesia; goal-directed fluid management; early removal of Foley
      catheter; early mobilization, and early oral nutrition. The ERAS approach has
      gradually evolved to become the standard of care in colorectal surgery and is
      presently being used in other specialty areas such as vascular surgery. Currently
      there is little evidence available for the implementation of ERAS in this field.
      We plan to conduct a systematic review of this literature with a view to
      incorporating ERAS principles into the management of major elective vascular
      surgery procedures. METHODS: We will search EMBASE (OVID, 1947 to June 2012),
      Medline (OVID, 1948 to June 2012), and Cochrane Central Register of Controlled
      Trials (Wiley, Issue 1, 2012). Searches will be performed with no year or
      language restrictions. For inclusion, studies must look at adult patients over 18
      years. Major elective vascular surgery includes carotid, bypass, aneurysm and
      amputation procedures. Studies must have evaluated usual care against an ERAS
      intervention in the preoperative, perioperative or postoperative period of care.
      Primary outcome measures are length of stay, decreased complication rate, and
      patient satisfaction or expectations. Only randomized controlled trials will be
      included. DISCUSSION: Most ERAS approaches have been considered in the context of
      colorectal surgery. Given the increasing use of multiple yet different aspects of
      this pathway in vascular surgery, it is timely to systematically review the
      evidence for their independent or combined outcomes, with a view to implementing
      them in this clinical setting. Results from this review will have important
      implications for vascular surgeons, anaesthetists, nurses, and other health care
      professionals when making evidenced-based decisions about the use of ERAS in
      daily practice.

PMID- 23121843
TI  - Making house calls on the community.

PMID- 23121844
TI  - Communicating results of community-based participatory research.

PMID- 23121845
TI  - Physician, researcher, neighbor--conflicting roles in community-based
      participatory research.

PMID- 23121846
TI  - Setting the agenda for community-based participatory research.

PMID- 23121847
TI  - The AMA Code of Medical Ethics' opinion on population-based genomic research.

PMID- 23121848
TI  - Improving institutional review of community-based participatory research
      applications.

PMID- 23121850
TI  - Routine HIV testing in older adults.

PMID- 23121849
TI  - Identifying the challenges in community-based participatory research
      collaboration.

PMID- 23121851
TI  - Genetic research among the Havasupai--a cautionary tale.

PMID- 23121852
TI  - Community-based participatory research and the academic system of rewards.

PMID- 23121853
TI  - "Vulnerable" populations--medicine, race, and presumptions of identity.

PMID- 23121855
TI  - A United Nations Global Health Panel for Global Health Governance.
AB  - The World Health Organization now relies upon voluntary contributions tied to
      specific projects, underwriting 75% of operations. A resulting cacophony of non
      governmental, foundation, and private sector actors have emerged overlapping and
      fractionating WHO programs. In this expanding world of "global health
      organizations," WHO's role must be redefined. We propose coordination of global
      health initiatives through a United Nations Global Health Panel with active
      participation of WHO. Given recent events, the UN is poised to take a greater
      leadership role in global health.

PMID- 23121856
TI  - Labor migration and child mortality in Mozambique.
AB  - Male labor migration is widespread in many parts of the world, yet its
      consequences for child outcomes and especially childhood mortality remain
      unclear. Male labor migration could bring benefits, in the form of remittances,
      to the families that remain behind and thus help child survival. Alternatively,
      the absence of a male adult could imperil the household's well-being and its
      ability to care for its members, increasing child mortality risks. In this
      analysis, we use longitudinal survey data from Mozambique collected in 2006 and
      2009 to examine the association between male labor migration and under-five
      mortality in families that remain behind. Using a simple migrant/non-migrant
      dichotomy, we find no difference in mortality rates across migrant and non
      migrant men's children. When we separated successful from unsuccessful migration
      based on the wife's perception, however, stark contrasts emerge: children of
      successful migrants have the lowest mortality, followed by children of non
      migrant men, followed by the children of unsuccessful migrants. Our results
      illustrate the need to account for the diversity of men's labor migration
      experience in examining the effects of migration on left-behind households.

PMID- 23121857
TI  - Social health insurance for the poor: targeting and impact of Indonesia's
      Askeskin programme.
AB  - A first step towards meeting Indonesia's ambition for universal health insurance
      was made in 2005 with the introduction of the Askeskin programme, a subsidized
      social health insurance targeted to the informal sector and the poor. This paper
      investigates targeting and impact of the Askeskin programme using panel data for
      8582 households observed in 2005 and 2006, and applying difference-in-differences
      estimation in combination with propensity score matching. We find that the
      programme is indeed targeted to the poor and those most vulnerable to
      catastrophic out-of-pocket health payments. Social health insurance improves
      access to health care in that it increases utilization of outpatient among the
      poor, while out-of-pocket spending seems to have increased for Askeskin insured
      in urban areas. 

PMID- 23121859
TI  - Neuropsychopharmacology across brain diseases.

PMID- 23121858
TI  - Physical co-morbidity among treatment resistant vs. treatment responsive patients
      with major depressive disorder.
AB  - Co-morbid physical illness has been suggested to play an important role among the
      factors contributing to treatment resistance in patients with major depressive
      disorder. In the current study we compared the rate of physical co-morbidity,
      defined by ICD-10, among a large multicenter sample of 702 patients with major
      depressive disorder. A total of 356 of the participants were defined as treatment
      resistant depression (TRD) patients-having failed two or more adequate
      antidepressant trials. No significant difference was found between TRD and non
      TRD participants in the prevalence of any ICD-10 category. This finding suggests
      that although physical conditions such as diabetes, thyroid dysfunction,
      hypertension, ischemic heart disease, and peptic diseases are often accompanied
      by co-morbid MDD, they do not necessarily have an impact on the course of MDD or
      the likelihood to respond to treatment. Marginally higher rates of co-morbid
      breast cancer, migraine and glaucoma were found among TRD participants. Possible
      explanations for these findings and their possible relation to TRD are discussed.

PMID- 23121860
TI  - Identification of a novel nuclear-localized adenylate kinase 6 from Arabidopsis
      thaliana as an essential stem growth factor.
AB  - Adenylate kinase (AK; EC 2.7.4.3) is highly conserved across a wide range of
      organisms, including Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila
      melanogaster, Arabidopsis thaliana, and Homo sapiens. While AK6 orthologs play
      important roles in the growth of yeast and worms, the physiological function of
      AK6 in A. thaliana is still unknown. In this study, we first cloned and expressed
      Arabidopsis adenylate kinase 6 (AAK6). Enzyme assays revealed that AAK6 has
      characteristic adenylate kinase properties, with ATP as the preferred phosphate
      donor and AMP as the best phosphate acceptor. A subcellular localization assay
      demonstrated that AAK6 had a predominant nuclear localization. Through
      biochemical purification and mass spectrometry analysis, a putative homolog of
      the S. cerevisiae Rps14 protein was identified as a partner of AAK6. Most
      importantly, we observed that aak6 T-DNA insertion mutants had decreased stem
      growth compared with wild-type plants. These data indicate that AAK6 exhibits
      adenylate kinase activity and is an essential growth factor in Arabidopsis.

PMID- 23121861
TI  - Purification and chemical characterisation of a cell wall-associated beta
      galactosidase from mature sweet cherry (Prunus avium L.) fruit.
AB  - Using four different chromatographic steps, beta-galactosidase was purified from
      the ripe fruit of sweet cherry to apparent electrophoretic homogeneity with
      approximately 131-fold purification. The Prunus avium beta-galactosidase showed
      an apparent molecular mass of about 100 kDa and consisted of four different
      active polypeptides with pIs of about 7.9, 7.4, 6.9 and 6.4 as estimated by
      native IEF and beta-galactosidase-activity staining. The active polypeptides were
      individually excised from the gel and subjected to SDS-PAGE. Each of the four
      native enzymes showing beta-galactosidase activity was composed of two
      polypeptides with an estimated mass of 54 and 33 kDa. Both of these polypeptides
      were subjected to N-terminal amino acid sequence analysis. The 54 kDa polypeptide
      of sweet cherry beta-galactosidase showed a 43% identity with the 44 kDa subunit
      of persimmon and apple beta-galactosidases and the 48 kDa subunit of carambola
      galactosidase I. The sweet cherry beta-galactosidase exhibited a strict
      specificity towards p-nitrophenyl beta-D-galactopyranoside, a pH optimum of 4.0
      and K(m) and V(max) values of 0.42 mM and 4.12 mmol min(-1) mg(-1) of protein
      respectively with this substrate. The enzyme was also active towards complex
      glycans. Taken together the results of this study prompted a role for this class
      of enzymes on sweet cherry fruit ripening and softening.

PMID- 23121862
TI  - An emboligenic pulmonary abscess leading to ischemic stroke and secondary brain
      abscess.
AB  - BACKGROUND: Ischemic stroke by septic embolism occurs primarily in the context of
      infective endocarditis or in patients with a right-to-left shunt and formation of
      a secondary cerebral abscess is a rare event. Erosion of pulmonary veins by a
      pulmonary abscess can lead to transcardiac septic embolism but to our knowledge
      no case of septic embolic ischemic stroke from a pulmonary abscess with secondary
      transformation into a brain abscess has been reported to date. CASE PRESENTATION:
      We report the case of a patient with a pulmonary abscess causing a septic embolic
      cerebral infarction which then transformed into a cerebral abscess. After
      antibiotic therapy and drainage of the abscess the patient could be rehabilitated
      and presented an impressive improvement of symptoms. CONCLUSION: Septic embolism
      should be considered as cause of ischemic stroke in patients with pulmonary
      abscess and can be followed by formation of a secondary cerebral abscess. Early
      antibiotic treatment and repeated cranial CT-scans for detection of a secondary
      abscess should be performed.

PMID- 23121863
TI  - The accuracy of D-dimer testing in suspected pulmonary embolism varies with the
      Wells score.

PMID- 23121864
TI  - Goserelin cannot improve the weakness of a patient with kennedy disease after 40
      week administration.

PMID- 23121865
TI  - Stimulation of suicidal erythrocyte death by fumagillin.
AB  - Fumagillin, a cyclohexane isolated from fungus Aspergillus fumigatus, has anti
      infective and anti-cancer potency. Fumagillin is at least partially effective by
      inducing suicidal death or apoptosis. In analogy to apoptosis of nucleated cells,
      eryptosis is the suicidal death of erythrocytes characterized by cell shrinkage
      and cell membrane scrambling with phosphatidylserine exposure at the cell
      surface. Stimulators of eryptosis include increase of cytosolic Ca(2+)-activity
      ([Ca(2+)](i)) and ceramide. The present study explored whether fumagillin (5-100
      MUM) could stimulate eryptosis. To this end, [Ca(2+)](i) was estimated from Fluo3
      fluorescence, ceramide by utilizing specific antibodies, cell volume from forward
      scatter, phosphatidylserine exposure from annexin V binding and haemolysis from
      haemoglobin release. As a result, a 48-hr exposure to fumagillin significantly
      increased [Ca(2+)](i) (>=10 MUM), enhanced ceramide abundance (100 MUM),
      triggered annexin V binding (>=10 MUM) and decreased forward scatter (>=10 MUM).
      Fumagillin exposure was followed by slight but significant increase of
      haemolysis. Removal of extracellular Ca(2+) significantly blunted but did not
      abolish the effect of fumagillin (100 MUM) on annexin V binding. The present
      observations disclose a novel effect of fumagillin, that is, stimulation of
      eryptosis, paralleled by Ca(2+) entry, ceramide formation, phosphatidylserine
      exposure and decrease of cell volume.

PMID- 23121866
TI  - HLA-A*0201-restricted CD8+ T-cell epitopes identified in dengue viruses.
AB  - BACKGROUND: All four dengue virus (DV) serotypes (D1V, D2V, D3V and D4V) can
      cause a series of disorders, ranging from mild dengue fever (DF) to severe dengue
      hemorrhagic fever and dengue shock syndrome (DHF/DSS). Previous studies have
      revealed that DV serotype-specific CD8(+) T cells are involved in controlling DV
      infection. Serotype cross-reactive CD8(+) T-cells may contribute to the
      immunopathogenesis of DHF/DSS. The aim of the study was to identify HLA-A*0201
      binding peptides from four DV serotypes. We then examined their immunogenicity in
      vivo and cross-reactivity within heterologous peptides. METHODS: D1V-derived
      candidate CD8(+) T-cell epitopes were synthesized and evaluated for their
      affinity to the HLA-A*0201 molecule. Variant peptides representing heterologous
      D2V, D3V, D4V serotypes were synthesized. The immunogenicity of the high-affinity
      peptides were evaluated in HLA-A*0201 transgenic mice. RESULTS: Of the seven D1V
      derived candidate epitopes [D1V-NS4a(56-64)(MLLALIAVL), D1V-C(46-54)(LVMAFMAFL),
      D1V-NS4b(562-570)(LLATSIFKL), D1V-NS2a(169-177)(AMVLSIVSL), D1V-NS4a(140
      148)(GLLFMILTV), D1V-NS2a(144-152)(QLWAALLSL) and D1V-NS4b(183-191)(LLMRTTWAL)],
      three peptides [D1V-NS4a(140-148), D1V-NS2a(144-152) and D1V-NS4b(183-191)] had a
      high affinity for HLA-A*0201 molecules. Moreover, their variant peptides for D2V,
      D3V and D4V [D2V-NS4a(140-148)(AILTVVAAT), D3V-NS4a(140-148)(GILTLAAIV), D4V
      NS4a(140-148)(TILTIIGLI), D2V-NS2a(144-152)(QLAVTIMAI), D3V-NS2a(144
      152)(QLWTALVSL), D4V-NS2a(143-151)(QVGTLALSL), D2V-NS4b(182-190)(LMMRTTWAL), D3V
      NS4b(182-190) (LLMRTSWAL) and D4V-NS4b(179-187)(LLMRTTWAF)] also had a high
      affinity for HLA-A*0201 molecules. Furthermore, CD8+ T cells directed to these
      twelve peptides were induced in HLA-A*0201 transgenic mice following immunization
      with these peptides. Additionally, cross-reactivity within four peptides (D1V
      NS4b(183-191), D2V-NS4b(182-190), D3V-NS4b(182-190) and D4V-NS4b(179-187)) was
      observed. CONCLUSIONS: Two novel serotype-specific HLA-A*0201-restricted CD8(+) T
      cell epitopes (NS4a(140-148) and NS2a(144-152)) and one cross-reactive HLA-A*0201
      restricted CD8(+) T-cell epitopes which is similar to a previously identified
      epitope were identified in D1V-D4V. Combining prediction algorithms and HLA
      transgenic mice is an effective strategy to identify HLA-restricted epitopes.
      Serotype-specific epitopes would be used to determine the protective role of
      serotype-specific CD8(+) T cells, while cross-reactive epitopes may provide
      assistance in exploring the role of serotype cross-reactive CD8(+) T cells in the
      immunopathogenesis of DHF/DSS.

PMID- 23121867
TI  - Addiction therapeutics: obstacles and opportunities.

PMID- 23121868
TI  - How does deep brain stimulation work?

PMID- 23121869
TI  - Lifting the mood on treating fragile X.

PMID- 23121870
TI  - Pharmacologically prospective antibiotic agents and their sources: a marine
      microbial perspective.
AB  - Marine microbes have been a storehouse of bioactive metabolites with tremendous
      potential as drug candidates. Marine microorganism derived secondary metabolites
      (chemical compounds/peptides) are considered to be a burning area of research
      since recent past. Many of such compounds have been proven to be anti-bacterial,
      anti-fungal, anti-algal, anti-HIV, anti-helminthic, anti-protozoan, anti-tumor
      and anti-allergic agents. Marine bacteria and fungi have been reported to be the
      producers of such compounds owing to their defense mechanisms and metabolic by
      products. Although the number of natural products isolated from these classes of
      marine microbial flora is large, a limited number of such compounds reach the
      clinical trial and even less number of them get approved as a drug. Here we
      discuss the recent studies on the isolation, characterization and the
      pharmacological significances of anti-bacterial, anti-fungal and anti-infective
      agents of marine microbial origin. Further, the clinical status of such compounds
      has also been discussed in comparison with those derived from their terrestrial
      counterparts.

PMID- 23121871
TI  - Biomarker responses in mudskipper (Periophthalmus waltoni) from the coastal areas
      of the Persian Gulf with oil pollution.
AB  - A suite of 5 different biomarker responses were selected and measured in 3
      different phases of detoxification process in mudskipper Periophthalmus waltoni
      from 3 different stations including Soltani Inlet, Shif Island and Ameri Port in
      Bushehr coastal area of the Persian Gulf. The selected biomarkers were 7
      ethoxyresorufin O-deethylase (EROD), glutathione S-transferase (GST), biliary
      fluorescent aromatic compounds (FACs), DNA damage using the Comet assay and
      micronucleus (MN). Spatial variations in biomarker responses were observed in
      different sites. EROD, GST, FACs, DNA damage and MN were significantly elevated
      in mudskippers in the most oil impacted site (Soltani inlet). Based on the
      assessments, bile metabolites, EROD and GST induction appear to be sensitive to
      polycyclic aromatic hydrocarbons (PAHs) and can be considered as complementary
      biomarkers; therefore P. waltoni has the potential to be used as a bioindicator
      in these types of ecosystems.

PMID- 23121872
TI  - Exposure to nickel by hair mineral analysis.
AB  - The aim of the present work was to investigate the exposure to nickel from
      various sources by investigation of mineral composition of human scalp hair. The
      research was carried out on hair sampled from subjects, including 87 males and
      178 females (22 +/- 2 years). The samples of hair were analyzed by ICP-OES. The
      effect of several factors on nickel content in hair was examined: lifestyle
      habits (e.g. hair coloring, hair spray, hair straighteners, hair drier, drugs);
      dietary factors (e.g. yoghurts, blue cheese, lettuce, lemon, mushroom, egg,
      butter); other (e.g. solarium, cigarette smoking, tap water pipes, tinned food,
      PVC foil, photocopier, amalgam filling). These outcomes were reached by linking
      the results of nickel level in hair with the results of questionnaire survey.
      Basing on the results it can be concluded that exposure to nickel ions can occur
      from different sources: lifestyle, eating habits and environmental exposure.

PMID- 23121873
TI  - Preventive effect of phycocyanin from Spirulina platensis on alloxan-injured
      mice.
AB  - The preventive effect of phycocyanin (obtained from Spirulina platensis) on
      alloxan-injured mice is investigated. Oral administration of phycocyanin was
      started two weeks before an alloxan injury and continued until four weeks later.
      Tests resulted in the following positive results of oral phycocyanin
      administration on alloxan-injured mice: decrease fasting blood glucose and
      glycosylated serum protein (GSP); maintain total antioxidative capability (T
      AOC); avert malondialdehyde (MDA) formation in the liver, kidney, and pancreas;
      decrease total cholesterol (TC) level and triglycerides (TG) level in serum and
      liver; increase the levels of hepatic glycogen level; maintain glucokinase (GK)
      expression in the liver and decrease p53 expression in the pancreas at mRNA
      level. The histological observations also supported the above results. Acute
      toxicity study further shows that phycocyanin is relatively safe. These results
      led to the conclusion that phycocyanin has significant preventive effect on
      alloxan-injured mice. The inhibition of p53 pathway could be one of the
      mechanisms that led to the protection of pancreatic islets from alloxan injury.
      We also proposed that GK expression that functions to promote liver glycogen
      synthesis could be the reason for reduced blood glucose level. The encouraging
      results are the first step in studying the potential of phycocyanin as a clinical
      measure in preventing diabetes.

PMID- 23121874
TI  - Activation of the Ahr signalling pathway by polychlorobiphenyls causes a marked
      induction of cytochrome P450 only after depletion of vitellogenin in Sparus
      aurata.
AB  - The effects of polychlorinated biphenyl congeners 126 and 153 (PCB-126 and PCB
      153) on vitellogenin (Vtg) and cytochrome (CYP1A1) expression were evaluated in
      60 juvenile Sparus aurata. Fish were divided into four groups and the control
      group (Group A) was compared to fish exposed to PCB-126 (10-8M) (Group B), PCB
      153 (10-6M) (Group C) singly and also in combination (Group D) for 12, 24 and 72
      h. Hepatic expression of Vtg and CYP1A1 were analyzed using histological
      examinations and by immunochemical (Western blotting and immunohistochemistry)
      methods. Vtg increased in juvenile fishes of Groups B, C and D after 12h respect
      to Group A and decreased after 24 and 72 h respect to 12h in each group. CYP1A1
      increased after 12 and 24h in all groups vs control group and increased in Group
      B only at 72 h vs in control group. The results showed that chemical interaction
      and endocrine disruption in fish might produce deleterious consequences not only
      for fish but also for human.

PMID- 23121875
TI  - Asthma in late adolescents of Western Mexico: prevalence and associated factors.
AB  - INTRODUCTION: Given the number of changes that occur during late adolescence, it
      is possible that the behavior of asthma may also be different. The aim of our
      paper is to determine the prevalence of asthma in a population of late
      adolescents and its possible association with obesity, tobacco smoke exposure and
      family history of allergic disease. METHODS AND SUBJECTS: In a cross-sectional,
      population-based analytical study design, we selected a stratified random sample
      of subjects aged 15 to 18. By modeling risk through logistic regression, we
      assessed the relationship between asthma and the following covariables: gender,
      obesity, excess weight, family history of allergic disease and tobacco smoke
      exposure. RESULTS: 1,600 subjects were included, and the following prevalences
      were identified: asthma 7.8%, obesity 9.6%, active smoking in the father 2 9.8%,
      active smoking in the mother 18.6% and active smoking habit in the study subjects
      15.1%. In the final model, a significant association was found between asthma and
      the following variables: 1) asthma in the mother (adjusted OR [aOR]=2.95, 95% CI,
      1.55 to 5.6); 2) history of allergic rhinitis (aOR=4.66, 95% CI, 2.63 to 8.25);
      and 3) male sex (aOR=1.48, 95% CI, 1.02 to 2.15). No association was seen with
      obesity or tobacco smoking of the parents. CONCLUSION: Our results suggest that
      maternal history of asthma, personal history of allergic rhinitis and male sex
      are related with asthma late adolescence, while smoking and being overweight are
      not.

PMID- 23121876
TI  - Pulmonary sequestration.

PMID- 23121877
TI  - [Study to assess the level of knowledge of the Security Law in nurses].
AB  - Proposal of  the recent Security Law, which regulates access of irregular
      immigrants to health services , provoked much debate and uprising. However,
      little attention was  paid to its approval, after substantial modification. This
      study was performed to assess how much nurses know about this law, by means of a
      questionnaire issued to  200 nurses working in one hospital.  Results showed that
      they had been informed by the media, 51% were aware that the law regards both
      physicians and nurses and 40% stated that  immigrants were not obliged to present
      identification. Only 19% of the sample correctly  stated that denouncement to the
      authorities is not obligatory; the remaining 81% believed the contrary to be true
      . A need for greater information was expressed by 72%.   The outcome of the study
      confirmed the need for greater information on this topic.

PMID- 23121878
TI  - [Safe medication administration in operating rooms: observational study].
AB  - Administration of medication in an environment such as operating rooms is
      extremely complex  and considerably increases the possibility of errors . This
      study was performed to analyze how  medication is stored, prescribed and
      administered in operating rooms. Eight operating rooms in a Northern Italy
      hospital were taken into consideration, analyszing the medication prescribed in
      96 working days. The critical points that emerged from the study regarded tasks
      performed by nurses , but also other professionals.  This pilot study was useful
      for acquiring basic data on the working processes that surround the
      administration of medication.

PMID- 23121879
TI  - [Awareness of diagnosis and prognosis in patients with unfavorable prognosis:
      perception of the attitudes of a group of doctors and nurses].
AB  - In oncological patients , communication of the diagnosis of the disease or its
      regression and the patient's awareness of both diagnosis and prognosis, plays a
      central role. Up to a few decades ago , it was common practice not to reveal the
      diagnosis of cancer. Nowadays, the situation has changed owing to radical socio
      cultural changes. However, in daily practice, the most frequent impression is
      that the patient does not entirely realize the implications of diagnosis and
      prognosis  and health workers find it difficult to inform patients clearly and
      honestly so that they can decide which cures to accept or decline.  An
      observational study was performed on a group of 153 doctors and nurses  to
      identify their opinions and attitudes  regarding how to inform cancer patients,
      in terms of diagnosis and prognosis,  and how they perceived the  level of
      awareness in such patients. The results of the study partly confirmed published
      data , in that both doctors and nurses  thought it best to inform the patient of
      the oncological pathology, keeping back the unfavorable prognosis and that the
      percentage of patients really made aware of these implications was lower than
      officially declared.

PMID- 23121880
TI  - [Exploring moral distress among clinical nurses].
AB  - Moral distress in nursing practice is described as a suffering situation that
      arises when the nurse is unable to act her/his ethical choices, when
      institutional constraints interfere with acting in the way she/he believes to be
      right. The aim is to describe nursing practice situations causing moral distress
      resulting from the recognition of the ethical appropriate actions combined with
      the impossibility to pursue it; to describe how nurses manage moral distress
      situations and the strategies to cope with them. A focus group was conducted in
      three wards of a large teaching-hospital in the north of Italy. In another ward
      the nurses were asked to write a moral distress experience. A total of 40 nurses
      were involved and 50 experiences collected. The experiences' analysis has shown 5
      source areas of moral distress: 1) clinical decision; 2) nursing competences; 3)
      nurse-physician collaboration;  4) organization of care; 5) safe care. For each
      area the most  frequent themes were highlighted.Areas of clinical decision,
      nursing competences, nurse-physician collaboration involve nurse leaders in
      identification and implementation of strategies for managing moral  distress.

PMID- 23121881
TI  - [Moral distress in nursing care].
AB  - In nursing practice, the ability to make decisions regarding patients and to act
      on them is considered to be an expression of the professional nursing role.
      Problems may arise when a nurses would like to perform an action they believe
      morally correct but which are conflictual with the habits, organization or
      politics of the health structure in which they work. This inevitably produces
      moral distress in nurses who feel impotent to act as they feel they should.
      Although a certain amount of moral distress is part and parcel of the nursing
      profession , when it is excessive or prolonged it may become unacceptable and
      culminate in burn-out and the relative consequences. The aim of the study was to
      compare the level of moral stress in 111 Italian nurses working in different
      Operative Units to identify those clinical situations significantly associated
      with moral stress using the MDS scale. Similarly to studies performed in the USA,
      the level of moral stress in the 3 different work contexts was moderate, although
      some clinical situations were related to significant stress levels.

PMID- 23121882
TI  - [Living Will: a conscious choice? Survey on knowledge of Italian people].
AB  - In a scientifically and technologically advanced context, where it is possible to
      postpone death at our will, the life will may be a tool for guaranteeing the
      patient's right and freedom to decide on whether and how to be cured. Debate
      regarding the life will is extremely important but a very delicate issue. This
      study describes the results of  a survey  performed on 200 people living in
      Central Italy using an ISPO 2009 questionnaire.Its aims were:  to analyze the
      feelings of Italians on the questions surrounding the end of life;  examine the
      doctor-patient relationship and the life will;  find out how knowledge has
      changed since 2009;  record opinions on a law governing the life will  and how
      opinions have changed since 2009. Results showed that knowledge of the life will
      and its various aspects was severely lacking and that there has been no
      improvement in such  knowledge since 2009 . There is a significant gap to be
      filled  regarding end of life issues and, given their constant presence at this
      time,  nurses could play an important role.

PMID- 23121883
TI  - Right to life, right to end of life: some considerations.
AB  - Human rights have undergone constant evolution. Recently, however, new
      generations of rights are developing: from political and civil rights to social
      and economic rights, so much so that this period may be defined as the age of
      human rights.  Many differences exist between moral rules and judicial law. While
      moral rights are not necessarily recorded in statutory law, some judicial laws,
      which are capable of being imposed and/or appealed within a true territorial
      government, originate from moral rules.  Common sense has reservations about
      whether human rights can be labelled as laws in a rudimentary way; instead,
      society places human rights in the category of moral rights. These moral rights,
      in fact, are not the fruit of compromise, but are absolute and essential to the
      inner self. Throughout this article, the evolution of  end of life rights  is
      discussed, with particular regard to how those rights are directly correlated to
      organ transplantation.

PMID- 23121885
TI  - Marine mercury fate: from sources to seafood consumers.

PMID- 23121884
TI  - Investigation of Caucasian rheumatoid arthritis susceptibility loci in African
      patients with the same disease.
AB  - INTRODUCTION: The largest genetic risk to develop rheumatoid arthritis (RA)
      arises from a group of alleles of the HLA DRB1 locus ('shared epitope', SE). Over
      30 non-HLA single nucleotide polymorphisms (SNPs) predisposing to disease have
      been identified in Caucasians, but they have never been investigated in
      West/Central Africa. We previously reported a lower prevalence of the SE in RA
      patients in Cameroon compared to European patients and aimed in the present study
      to investigate the contribution of Caucasian non-HLA RA SNPs to disease
      susceptibility in Black Africans. METHODS: RA cases and controls from Cameroon
      were genotyped for Caucasian RA susceptibility SNPs using Sequenom MassArray
      technology. Genotype data were also available for 5024 UK cases and 4281 UK
      controls and for 119 Yoruba individuals in Ibadan, Nigeria (YRI, HapMap). A
      Caucasian aggregate genetic-risk score (GRS) was calculated as the sum of the
      weighted risk-allele counts. RESULTS: After genotyping quality control procedures
      were performed, data on 28 Caucasian non-HLA susceptibility SNPs were available
      in 43 Cameroonian RA cases and 44 controls. The minor allele frequencies (MAF)
      were tightly correlated between Cameroonian controls and YRI individuals
      (correlation coefficient 93.8%, p = 1.7E-13), and they were pooled together.
      There was no correlation between MAF of UK and African controls; 13 markers
      differed by more than 20%. The MAF for markers at PTPN22, IL2RA, FCGR2A and
      IL2/IL21 was below 2% in Africans. The GRS showed a strong association with RA in
      the UK. However, the GRS did not predict RA in Africans (OR = 0.71, 95% CI 0.29 -
      1.74, p = 0.456). Random sampling from the UK cohort showed that this difference
      in association is unlikely to be explained by small sample size or chance, but is
      statistically significant with p<0.001. CONCLUSIONS: The MAFs of non-HLA
      Caucasian RA susceptibility SNPs are different between Caucasians and Africans,
      and several polymorphisms are barely detectable in West/Central Africa. The
      genetic risk of developing RA conferred by a set of 28 Caucasian susceptibility
      SNPs is significantly different between the UK and Africa with p<0.001. Taken
      together, these observations strengthen the hypothesis that the genetic
      architecture of RA susceptibility is different in different ethnic backgrounds.

PMID- 23121886
TI  - Metal bioavailability from different natural prey to a marine predator Nassarius
      siquijorensis.
AB  - Gastropods are often the top predators in marine benthic environments, and
      trophic transfer is the predominant route by which metals are accumulated in
      these predators. In the present study, the potential influences of prey
      composition on the trophic transfer, accumulation, subcellular distribution and
      metallothionein induction of six metals (Ag, As, Cd, Cu, Pb and Zn) in a predator
      Nassarius siquijorensis were investigated. The snails were fed venerid clams
      Ruditapes philippinarum, mussels Perna viridis, oysters Crassostrea angulata or
      barnacles Fistulobalanus albicostatus, each differing greatly in their metal
      accumulation and handling patterns. N. siquijorensis showed prey-specific
      bioaccumulation and trophic transfer of the six metals. In general, the body
      burdens of metals in the viscera and muscles of N. siquijorensis increased with
      increasing exposure period and metal concentration in the four prey. The
      calculated trophic transfer factors (TTFs) of the metals in different prey varied
      and were the highest for clams and mussels prey, indicating that metal
      bioavailability from these prey was higher than that from barnacles and oysters.
      All the studied metals except Pb were enriched during transfer to the snails. The
      subcellular metal distribution in the viscera was affected by prey composition.
      Exposure to the four natural prey induced MTs, which may be used as a better
      biomarker for muscle than for viscera for metal stress. Our results imply that
      metals from different natural prey have different bioavailability and may help
      better understand the trophic transfer of metals in marine benthic food chain.

PMID- 23121887
TI  - Bee venom ameliorates ovalbumin induced allergic asthma via modulating CD4+CD25+
      regulatory T cells in mice.
AB  - Asthma is a potentially life-threatening inflammatory disease of the lung
      characterized by the presence of large numbers of CD4+ T cells. These cells
      produce the Th2 and Th17 cytokines that are thought to orchestrate the
      inflammation associated with asthma. Bee venom (BV) has traditionally been used
      to relieve pain and to treat chronic inflammatory diseases. Recent reports have
      suggested that BV might be an effective treatment for allergic diseases. However,
      there are still unanswered questions related to the efficacy of BV therapy in
      treating asthma and its therapeutic mechanism. In this study, we evaluated
      whether BV could inhibit asthma and whether BV inhibition of asthma could be
      correlated with regulatory T cells (Treg) activity. We found that BV treatment
      increased Treg populations and suppressed the production of Th1, Th2 and Th17
      related cytokines in an in vitro culture system, including IL2, IL4, and IL17.
      Interestingly, production of IL10, an anti-inflammatory cytokine secreted by
      Tregs, was significantly augmented by BV treatment. We next evaluated the effects
      of BV treatment on allergic asthma in an ovalbumin (OVA)-induced mouse model of
      allergic asthma. Cellular profiling of the bronchoalveolar lavage (BAL) and
      histopathologic analysis demonstrated that peribronchial and perivascular
      inflammatory cell infiltrates were significantly lowered following BV treatment.
      BV also ameliorated airway hyperresponsiveness, a hallmark symptom of asthma. In
      addition, IL4 and IL13 levels in the BAL fluid were decreased in the BV treated
      group. Surprisingly, the beneficial effects of BV treatment on asthma were
      eradicated following Treg depletion by anti-CD25 antibody injection, suggesting
      that the major therapeutic targets of BV were Tregs. These results indicate that
      BV efficiently diminishes bronchial inflammation in an OVA-induced allergic
      asthma murine model, and that this effect might correlate with Tregs, which play
      an important role in maintaining immune homeostasis and suppressing the function
      of other T cells to limit the immune response. These results also suggest that BV
      has potential therapeutic value for controlling allergic asthma responses.

PMID- 23121888
TI  - Accuracy of the point-of-care coagulometer CoaguChek XS in the hands of patients.

PMID- 23121889
TI  - ATP13A2 knockout does not affect the infarct size in mice with acute ischemic
      stroke.

PMID- 23121890
TI  - Tire traces - discrimination and classification of pyrolysis-GC/MS profiles.
AB  - Tire traces can be observed on several crime scenes as vehicles are often used by
      criminals. The tread abrasion on the road, while braking or skidding, leads to
      the production of small rubber particles which can be collected for comparison
      purposes. This research focused on the statistical comparison of Py-GC/MS
      profiles of tire traces and tire treads. The optimisation of the analytical
      method was carried out using experimental designs. The aim was to determine the
      best pyrolysis parameters regarding the repeatability of the results. Thus, the
      pyrolysis factor effect could also be calculated. The pyrolysis temperature was
      found to be five time more important than time. Finally, a pyrolysis at 650
      degrees C during 15s was selected. Ten tires of different manufacturers and
      models were used for this study. Several samples were collected on each tire, and
      several replicates were carried out to study the variability within each tire
      (intravariability). More than eighty compounds were integrated for each analysis
      and the variability study showed that more than 75% presented a relative standard
      deviation (RSD) below 5% for the ten tires, thus supporting a low
      intravariability. The variability between the ten tires (intervariability)
      presented higher values and the ten most variant compounds had a RSD value above
      13%, supporting their high potential of discrimination between the tires tested.
      Principal Component Analysis (PCA) was able to fully discriminate the ten tires
      with the help of the first three principal components. The ten tires were finally
      used to perform braking tests on a racetrack with a vehicle equipped with an anti
      lock braking system. The resulting tire traces were adequately collected using
      sheets of white gelatine. As for tires, the intravariability for the traces was
      found to be lower than the intervariability. Clustering methods were carried out
      and the Ward's method based on the squared Euclidean distance was able to
      correctly group all of the tire traces replicates in the same cluster than the
      replicates of their corresponding tire. Blind tests on traces were performed and
      were correctly assigned to their tire source. These results support the
      hypothesis that the tested tires, of different manufacturers and models, can be
      discriminated by a statistical comparison of their chemical profiles. The traces
      were found to be not differentiable from their source but differentiable from all
      the other tires present in the subset. The results are promising and will be
      extended on a larger sample set. 

PMID- 23121891
TI  - Contributory factors in herb-induced fatal aconite poisoning.
AB  - Detailed investigations of all reported cases of herb-induced aconite poisoning
      are necessary to identify the major contributory causes so that preventive
      measures can be formulated. In the present review of 12 fatal cases that were
      published in the medical journals during 1992 and 2011, the available clinical
      data and forensic toxicological analyses indicated that poor post-harvest
      processing of aconite roots, use of greater than the recommended doses and
      inadequate boiling of processed aconite roots during decoction preparation were
      important contributory factors in herb-induced aconite poisoning. Under such
      circumstances, the actual amount of Aconitum alkaloids ingested was much larger
      than intended. Good manufacturing practice to ensure adequate processing of
      aconite roots, use of the recommended doses, clear instructions for the patients
      and their compliance during decoction preparation are important preventive
      measures.

PMID- 23121892
TI  - Spontaneous dissection of the coronary and vertebral arteries post-partum: case
      report and review of the literature.
AB  - BACKGROUND: Spontaneous coronary and vertebral artery dissections are rare events
      occurring most commonly in otherwise healthy women during pregnancy or the post
      partum period. CASE PRESENTATION: This report describes a 35-year-old female who
      presented with an acute inferior ST elevation myocardial infarction 7 months post
      partum secondary to spontaneous dissection of the left obtuse marginal coronary
      artery. Despite appropriate medical therapy with dual anti-platelet therapy, the
      patient presented four weeks later with a spontaneous dissection of the right
      vertebral artery. CONCLUSION: We review the presentation, diagnosis, and
      management of spontaneous dissections of the vasculature in the peri-partum
      period.

PMID- 23121894
TI  - Brain Research special issue: advances in the neuroscience of tinnitus.

PMID- 23121893
TI  - Primary bladder adenocarcinoma versus metastatic colorectal adenocarcinoma: a
      persisting diagnostic challenge.
AB  - AIM: This study attempted to distinguish primary bladder adenocarcinoma (PBA)
      from metastatic colonic adenocarcinomas (MCA), which is a difficult diagnostic
      and clinical problem. METHODS: Twenty-four cases of bladder adenocarcinomas (12
      primary & 12 metastatic colorectal) were included in the study with urothelial
      carcinoma (UC) and colonic adenocarcinoma (CA) as controls. A panel of
      immunohistochemical (IHC) stains along with fluorescence in-situ hybridization
      (FISH), using the UroVysion probe set, was performed. RESULTS: The majority of
      the PBAs presented with advanced disease. Enteric histologic subtype was the most
      common morphological variant. Strong nuclear with cytoplasmic-membranous staining
      of beta-catenin was seen in 75% of MCA and only 16.7% PBA (<10% staining cells).
      Although abnormal nuclear staining with E-cadherin was seen in both PBA and MCA,
      it was more frequent in former. CK-7, CK-20, villin and CDX-2 stains were not
      helpful in distinguishing the two entities. FISH did not reveal any unique
      differences in chromosomal abnormality between the two groups. CONCLUSION:
      Although there was a statistically significant difference in beta-catenin and E
      cadherin staining between two groups, we did not find any IHC or FISH marker that
      was specific for PBA. Distinction between PBA and MCA remains a diagnostic
      problem and clinical correlation is vital before rendering a diagnosis. VIRTUAL
      SLIDES: The virtual slides for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1393156268152357.

PMID- 23121895
TI  - Sieving wastewater--cellulose recovery, economic and energy evaluation.
AB  - Application of fine-mesh sieves (<0.35 mm) as pretreatment for municipal
      biological wastewater treatment gives an opportunity to recover resources and
      increase sustainability of wastewater treatment processes. Sieves are
      traditionally used for single stage mechanical treatment (typical mesh of 0.35
      mm) or in combination with an MBR (typical mesh >0.7 mm). When sieves with a mesh
      of 0.35 mm are used on raw sewage we observed that cellulose fibres mainly
      originating from toilet paper are removed efficiently from the influent with a
      high recovery and purity. The application of sieves as pretreatment for
      conventional activated sludge processes has been evaluated based on pilot plant
      research at three WWTPs in the Netherlands. With sieving applied to the dry
      weather flow only the overall energy usage of the WWTP including sludge treatment
      can be decreased by at least 40% with a payback time of 7 years.

PMID- 23121896
TI  - A three-electrode column for Pd-catalytic oxidation of TCE in groundwater with
      automatic pH-regulation and resistance to reduced sulfur compound foiling.
AB  - A hybrid electrolysis and Pd-catalytic oxidation process is evaluated for
      degradation of trichloroethylene (TCE) in groundwater. A three-electrode, one
      anode and two cathodes, column is employed to automatically develop a low pH
      condition in the Pd vicinity and a neutral effluent. Simulated groundwater
      containing up to 5 mM bicarbonate can be acidified to below pH 4 in the Pd
      vicinity using a total of 60 mA with 20 mA passing through the third electrode.
      By packing 2 g of Pd/Al(2)O(3) pellets in the developed acidic region, the column
      efficiency for TCE oxidation in simulated groundwater (5.3 mg/L TCE) increases
      from 44 to 59 and 68% with increasing Fe(II) concentration from 0 to 5 and 10
      mg/L, respectively. Different from Pd-catalytic hydrodechlorination under
      reducing conditions, this hybrid electrolysis and Pd-catalytic oxidation process
      is advantageous in controlling the fouling caused by reduced sulfur compounds
      (RSCs) because the in situ generated reactive oxidizing species, i.e., O(2),
      H(2)O(2) and OH, can oxidize RSCs to some extent. In particular, sulfite at
      concentrations less than 1 mM even greatly increases TCE oxidation by the
      production of SO(4)(*-), a strong oxidizing radical, and more OH.

PMID- 23121897
TI  - Two novel alleles at HLA-B locus identified in two volunteer bone marrow donors
      by sequence-based typing.
AB  - Two novel human leucocyte antigen (HLA) class I alleles have been identified in
      two Italian individuals. HLA-B*27:07:02 is identical to HLA-B*27:07:01 except for
      a nucleotide substitution at position 846 (A->G) resulting in a silent mutation.
      HLA-B*35:206 differs from the most similar allele, HLA-B*35:08:01, because of a
      single base mutation at position 149 (G->C) causing an aminoacidic change at
      codon 26 from Gly to Ala. 

PMID- 23121898
TI  - Ocular vestibular evoked myogenic potentials induced by air-conducted sound in
      patients with acute brainstem lesions.
AB  - OBJECTIVE: The ocular vestibular-evoked myogenic potential (oVEMP), a recently
      documented otolith-ocular reflex, is considered to reflect the central
      projections of the primary otolithic afferent fibers to the oculomotor nuclei.
      The aim of our study is to define air-conducted sound oVEMP abnormality in
      patients with acute brainstem lesions and to determine the brainstem structures
      involved in the generation of oVEMPs. METHODS: In response to air-conducted tone
      burst sounds (ACS), oVEMP was measured in 52 patients with acute brainstem
      lesions. Individualized brainstem lesions were analyzed by means of MRI-based
      voxel-wise lesion-behavior mapping, and the probabilistic lesion maps were
      constructed. RESULTS: More than half (n=28, 53.8%) of the patients with acute
      brainstem lesions showed abnormal oVEMP in response to ACS. The majority of
      patients with abnormal oVEMPs had lesions in the dorsomedial brainstem that
      contains the medial longitudinal fasciculus (MLF), the crossed ventral tegmental
      tract (CVTT), and the oculomotor nuclei and nerves. CONCLUSION: MLF, CVTT, and
      the oculomotor nuclei and nerves appear to be responsible for otolith-ocular
      responses in the brainstem. SIGNIFICANCE: Complemented to cervical VEMP for the
      uncrossed otolith-spinal function, oVEMP to ACS may be applied to evaluate the
      crossed otolith-ocular function in central vestibulopathies.

PMID- 23121899
TI  - Increased brain responses during subjectively-matched mechanical pain stimulation
      in fibromyalgia patients as evidenced by MEG.
AB  - OBJECTIVE: The precise pathophysiology of fibromyalgia, a syndrome characterized
      by chronic widespread pain, remains to be clarified. When subjected to the same
      amount of stimulation, patients show enhanced brain responses as compared to
      controls, providing evidence of central pain augmentation in this syndrome. We
      aimed to characterize brain response differences when stimulation is adjusted to
      elicit similar subjective levels of pain in both groups. METHODS:
      Magnetoencephalography (MEG) was used to investigate the brain responses to
      pressure stimulation applied both above and below the pain threshold in nine
      patients and nine control subjects. A device was developed to deliver pressure
      pulses in a quantifiable and precise manner. The amount of pressure was adjusted
      to produce similar subjective pain in both groups. RESULTS: A between-group
      comparison of differences between responses evoked by stimulation above and below
      the pain threshold was performed using cluster-based permutation testing.
      Increases in signal amplitude in somatosensory, temporal and parietal areas at
      short latencies, and in prefrontal areas at both short and long latencies, were
      found to be larger for patients than for control subjects. CONCLUSION:
      Fibromyalgia patients show enhanced brain responses after reducing the amount of
      pressure to produce similar subjective levels of pain than to the control
      subjects. SIGNIFICANCE: The present results suggest that central pain
      augmentation is present in fibromyalgia, not only when the objective level of
      stimulation is kept the same as for control subjects, but also when stimulation
      is adjusted to produce similar levels of pain in patients and controls.

PMID- 23121900
TI  - Issues in using air conducted sound to test oVEMPs.

PMID- 23121901
TI  - A robust implementation of a kurtosis beamformer for the accurate identification
      of epileptogenic foci.
AB  - OBJECTIVE: To improve the accuracy and reliability of the localisation of
      epileptogenic activity using spatially filtered MEG data. METHODS: A synthetic
      epileptic source was embedded in healthy brain activity in different orientations
      in order to estimate how reliably this signal containing high levels of kurtosis
      can be localised. An existing approach (SAM(g2)) was compared to a new
      implementation of the methodology. RESULTS: The results confirm that a kurtosis
      beamformer is an effective tool with which to localise spontaneous epileptiform
      activity. However, it is crucial that the orientation of source reconstruction
      matches that of the true source otherwise the epileptic activity is either mis
      localised or completely missed. Therefore as the original SAM(g2) implementation
      is restricted to the tangential plane, in certain circumstances it will perform
      poorly compared to the approach described here. CONCLUSIONS: A kurtosis
      beamformer is made more accurate and more robust if the analysis is not
      restricted to the tangential plane and if the optimisation routine for selecting
      the source orientation is performed using kurtosis rather than power.
      SIGNIFICANCE: MEG is increasingly being used for the non-invasive localisation of
      epileptic biomagnetic signals and the implementation described in this paper
      increases the clinical utility of the technique.

PMID- 23121902
TI  - [Abnormalities of the penis in boys].
AB  - Abnormalities of the male genitalia have increased in the last 2 decades in
      numerous developed countries and remain a frequent reason of consultation in
      pediatric surgery. The diagnostic spectrum is wide, and surgeons should pay
      particular attention to these abnormalities because of their potential
      psychological effect. Anatomically, these abnormalities can affect one of three
      parts of the penis. First, the foreskin may not be fully retracted. This is
      normal at birth and can be caused by prepuce adherents that can continue until
      adolescence. Today, true phimosis is treated with topical corticoids from the age
      of 3 years. If medical treatment fails, a surgical procedure is required. Second,
      the urethra can be affected by hypospadia, which is the most frequent abnormality
      of the urethra. It is associated with ectopic urethral meatus, hypoplastic
      foreskin, and penis curvature. Its pathogenic background is not clearly
      understood. Surgery options differ according to the type of hypospadia and
      according to the surgeon's experience. It is sometimes hard to deal with,
      especially in a perineal form, where genetic and hormonal studies are
      recommended. These interventions can lead to complications ranging from stenosis
      to fistula. Therefore, parents have to be informed of the benefits and risks of
      the surgical procedures. Epispadias is rare but more serious because of the
      increasing risk of urinary incontinence. Finally, abnormalities of the corpora
      cavernosa - often associated with hypospadias - can include penis curvature and
      micropenis, for which an endocrinological analysis is essential.

PMID- 23121903
TI  - [Lead poisoning in prevention and research].

PMID- 23121904
TI  - [The fight against tuberculosis in Denmark until 2050].

PMID- 23121905
TI  - [Continued problems with tuberculosis among Danes and Greenlanders in Denmark and
      the need for reinforced control--a systematic review].
AB  - Active transmission of Mycobacterium tuberculosis (Mt) continues at surprisingly
      high rates in Denmark. The transmission is particularly observed in specific high
      risk segments of the population with social problems such as homelessness,
      alcohol, and/or drug abuse. The patients are infected with the "Danish Cluster 2"
      Mt outbreak strain, and the transmission is attributed to delayed diagnosis. This
      situation demands increased focus on early tuberculosis diagnosis, control of
      transmission, and improved actions calls for prioritising the prevention and
      control of tuberculosis politically and economically.

PMID- 23121906
TI  - [Venereological examination].

PMID- 23121907
TI  - [Electronic monitoring of patients with bipolar affective disorder].
AB  - Bipolar disorder is a great challenge to patients, relatives and clinicians, and
      there is a need for development of new methods to identify prodromal symptoms of
      affective episodes in order to provide efficient preventive medical and
      behavioural intervention. Clinical trials prove that electronic monitoring is a
      feasible, valid and acceptable method. Hence it is recommended, that controlled
      trials on the effect of electronic monitoring on patients' course of illness,
      level of function and quality of life are conducted.

PMID- 23121908
TI  - [Hantavirus infection as the cause of haemorrhagic fever with renal syndrome].
AB  - Hantavirus is an RNA virus that can cause potentially fatal pulmonary and renal
      diseases in humans. Infections with Hantaviruses occur through inhalation of
      aerosol from rodent faeces, urine or saliva. The predominant virus type in
      Denmark is the Puumala virus, which causes the mildest form of haemorrhagic fever
      with renal syndrome, the so-called nephropathia epidemica (NE) with good
      prognosis (mortality 0.1-0.4%). The incidence of Hantavirus-infection in Denmark
      is about ten cases a year. The diagnosis of Hantavirus-infection is based on
      serology and/or polymerase chain reaction in blood or urine.

PMID- 23121909
TI  - [Renal failure in a couple caused by Puumala hantavirus].
AB  - In Scandinavia Puumala hantavirus causes nephropathia epidemica (NE),
      characterised by an acute debut of fever, headache, increasing back and abdominal
      pain, thrombocytopenia, increasing azotemia parameters, as well as microscopic
      haematuria and mild proteinuria. In some cases transitory myopia can be found.
      The diagnosis is made with a relevant clinical history and serology, and in most
      cases a kidney biopsy is not necessary. There is a risk of missing cases of NE as
      in this case, where a couple became infected by Puumala Hantavirus in a high-risk
      area but became ill in an area with a low prevalence.

PMID- 23121910
TI  - [Lateral humeral condyle fractures in children call for follow-up X-ray].
AB  - Lateral humeral condyle fractures are among the most common elbow fractures in
      children (20%), often in children aged six to ten years. X-rays of children this
      age are hard to interpret, and a seemingly undislocated fracture can still be
      unstable. Failure to recognise this problem can lead to the wrong treatment, non
      union and malfunction of the elbow.  An 11-year-old boy fell on his left arm. A
      plaster cast was administered and worn for four weeks without control X-ray. Four
      months later the boy had an extension defect of ten degrees, and a control
      computed tomography confirmed non-union.

PMID- 23121911
TI  - [Glandular tuberculosis as the cause of dysphagia].
AB  - Tuberculosis without pulmonal manifestation is uncommon, but must still be
      considered as differential diagnosis of lymphadenopathy. We present a case where
      the main symptom was dysphagia caused by a traction diverticulum due to glandular
      tuberculosis, which involved the lymph nodes in the neck. Based on the results of
      a magnetic resonance scanning and a computed tomography the primary diagnosis was
      a malignant oesophageal tumour, but a polymerase chain reaction on needle
      aspirated pus from a lymph node revealed a Mycobacterium tuberculosis complex. No
      malignant cells were found in an oesophageal biopsy. After anti-tuberculous
      treatment, the dysphagia resolved completely.

PMID- 23121912
TI  - [Immunoglobulin G4-related disease is a newly recognized inflammatory disease].
AB  - IgG4-related disease is a newly recognized inflammatory disease characterized by
      tissue infiltrates of IgG4 positive plasma cells. The disease was first
      recognized in pancreas but has now been described in nearly every organ. The
      diagnosis is based on the presence of dense lymphoplasmocytic infiltrates rich in
      IgG4 positive plasma cells. We describe a case of a 76-year-old man with IgG4
      related disease involving the kidneys.

PMID- 23121913
TI  - Muscle in heart disease: highlights from the European Society of Cardiology's
      Annual Meeting 2012.
AB  - Cardiac cachexia and alterations in muscle metabolism are a co-morbidity that can
      develop in advanced stages of chronic heart failure (HF). Up to 15% of ambulatory
      patients with HF are affected and present with a loss of different tissue types
      including muscle mass. Whilst cardiac cachexia has long been a neglected clinical
      entity, current HF guidelines of the European Society of Cardiology (ESC) include
      a section on weight management in patients with HF at risk of cardiac cachexia.
      This article highlights some recent studies of metabolic and functional
      alterations of the muscle in HF that were presented at the annual meeting of the
      ESC in August 2012 in Munich, Germany. The studies presented were focused on
      dysfunction of respiratory and limb skeletal musculature as well as metabolic
      features of myocardium in HF. Strategies improving muscle function and peak
      oxygen consumption in HF such as (inspiratory) muscle training and treatment of
      central sleep apnea by adaptive servoventilation are described. The latter shows
      promising results regarding HF symptoms and exercise capacity but still has to
      prove survival benefits in larger trials. A rat model highlights the value of
      microRNAs to regulate exercise-induced skeletal muscle angiogenesis. Another
      study provides evidence for changes in substrate utilisation depending on the
      functional status of mitochondria in the failing heart and points to
      mitochondrial dysfunction as a potential mediator of metabolic remodelling.
      Though treatments remain to be established, these findings may pave the way for
      effective therapeutic approaches to altered muscle function and cardiac cachexia.

PMID- 23121915
TI  - No train, no gain: does this apply to heart failure with preserved ejection
      fraction?

PMID- 23121916
TI  - Link between endocarditis on porcine bioprosthetic valves and allergy to pork.

PMID- 23121914
TI  - The past, present and future of renin-angiotensin aldosterone system inhibition.
AB  - The renin-angiotensin aldosterone system (RAAS) is central to the pathogenesis of
      cardiovascular disease. RAAS inhibition can reduce blood pressure, prevent target
      organ damage in hypertension and diabetes, and improve outcomes in patients with
      heart failure and/or myocardial infarction. This review presents the history of
      RAAS inhibition including a summary of key heart failure, myocardial infarction,
      hypertension and atrial fibrillation trials. Recent developments in RAAS
      inhibition are discussed including implementation and optimization of current
      drug therapies. Finally, ongoing clinical trials, opportunities for future trials
      and issues related to the barriers and approvability of novel RAAS inhibitors are
      highlighted. 

PMID- 23121919
TI  - Avian schistosomes and human cercarial dermatitis in a wildlife refuge in
      Mazandaran Province, northern Iran.
AB  - Each year, hundreds of aquatic migratory birds migrate from northern hemisphere
      to the Mazandaran Province, northern Iran. Little information is available on
      prevalence and density of schistosomes in water birds in Iran and around the
      world. The objectives of this study were to determine definitive and intermediate
      hosts of avian schistosomes as well as to assess human cercarial dermatitis (HCD)
      in a wildlife refuge in Mazandaran Province. Of 1106 examined people, 589 (53.2%)
      had maculopapular rashes mainly on feet but also on hand. The majority of cases
      were adults and local residents. Of 260 ducks, 41 (15.8%) were found to be
      infected with Trichobilharzia spp. eggs or adult worms. Prevalence was highest in
      Anas clypeata and Anas platyrhynchos, 79% and 18.9%, respectively. A total of
      1.2% snails, examined by both shedding and crushing methods, were infected with
      furcocercariae belonging to avian schistosomes. The most frequently infected
      snail was Lymnaea gedrosiana (5.9%). Our results showed that cercarial dermatitis
      and avian schistosomiasis is a common and yet neglected disease in this area.
      Anas clypeata played the most important role in exposing snails to miracidia in
      ponds and paddy fields. Moreover, because of the high prevalence in ducks and
      high prevalence of HCD in the region, it is considered as a new endemic focus in
      Iran. 

PMID- 23121918
TI  - Clinical relevance of microRNA miR-21, miR-31, miR-92a, miR-101, miR-106a and miR
      145 in colorectal cancer.
AB  - BACKGROUND: MicroRNAs (miRNAs) regulate gene expression by binding to mRNA, and
      can function as oncogenes or tumor suppressors depending on the target. In this
      study, using qRT-PCR, we examined the expression of six miRNAs (miR-21, miR-31,
      miR-92a, miR-101, miR-106a and miR-145) in tumors from 193 prospectively
      recruited patients with colorectal cancer, and associations with
      clinicopathological parameters and patient outcome were analyzed. The miRNAs were
      chosen based on previous studies for their biomarker potential and suggested
      biological relevance in colorectal cancer. METHODS: The miRNA expression was
      examined by qRT-PCR. Associations between miRNA expression and
      clinicopathological variables were explored using Mann-Whitney U and Kruskal
      Wallis test while survival was estimated using the Kaplan-Meier method and
      compared using the log-rank test. RESULTS: MiR-101 was hardly expressed in the
      tumor samples, while for the other miRNAs, variable expression levels and
      expression ranges were observed, with miR-21 being most abundantly expressed
      relative to the reference (RNU44). In our study cohort, major clinical
      significance was demonstrated only for miR-31, as high expression was associated
      with advanced tumor stage and poor differentiation. No significant associations
      were found between expression of the investigated miRNAs and metastasis-free or
      overall survival. CONCLUSIONS: Investigating the expression of six miRNAs
      previously identified as candidate biomarkers in colorectal cancer, few
      clinically relevant associations were detected in our patient cohort. Our results
      emphasize the importance of validating potential tumor markers in independent
      patient cohorts, and indicate that the role of miRNAs as colorectal cancer
      biomarkers is still undetermined.

PMID- 23121920
TI  - Evaluation of ceruloplasmin levels in patients undergoing surgical interventions
      with nasal polyps.
AB  - OBJECTIVE: Oxidative stress is believed to have a role in the development of
      nasal polyps (NPs). It is also known that ceruloplasmin (CP), an acute phase
      protein, limits oxidative stress. The purpose of this study was to evaluate the
      ceruloplasmin levels in patients with NPs. METHODS: One hundred and twenty
      patients with NPs, septal deviations and concha hypertrophies were recruited to
      the study. Patients were divided in two groups; group 1 (n=60) consisted of
      patients with NPs, and group 2 (n=60) consisted of septal deviations and concha
      hypertrophies. Polyp specimens were taken from all patients who underwent
      endoscopic surgery due to NPs, as well as control specimens were acquired who
      underwent an operation due to septoplasty or concha hypertrophy. Blood and tissue
      samples were obtained to assess CP levels. RESULTS: There were no statistical
      differences in gender, age and biochemical values between two groups (p>0.05 for
      all). Compared to group 2, group 1 had significantly higher CP levels both in
      serum and the tissue samples (both p<0.001). CONCLUSION: As a result of our
      study; CP levels both in serum and the tissue in patients with NPs were higher,
      may be consequence of the inflammation, than in patients without NPs.

PMID- 23121922
TI  - [Epidemiology Network and Information nephrology: REIN report 2010. editorial].

PMID- 23121921
TI  - Inhibitory effects of catechin derivatives on mammalian DNA polymerase and
      topoisomerase activities and mouse one-cell zygote development.
AB  - In this study, the inhibitory activities against DNA polymerases (pols) and DNA
      topoisomerases (topos) by eight major green tea catechin derivatives (flavan-3
      ols) were investigated. Some catechins inhibited mammalian pols (alpha and beta)
      and human topos (I and II), with (-)-epigallocatechin gallate (EGCg) the
      strongest inhibitor of both enzyme types, showing IC(50) values of 3.8-21.5 and
      2.0-20.0 MUM, respectively. EGCg did not affect the activities of plant
      (cauliflower) pol alpha or prokaryotic pols and showed no effect on the
      activities of other DNA metabolic enzymes tested. Next, a method was established
      for assay of mouse one-cell zygote development inhibition, the catechin
      derivatives screened for bioactivity, and the inhibition was assessed and their
      effects ranked as: EGCg > GCg > Cg >> others. In the mouse one-cell zygote assay,
      EGCg at 50 MUM increased abnormal cells and 75 MUM of EGCg-induced apoptosis. The
      observed ranking of catechin derivative inhibition effects against mouse one-cell
      zygote development in vivo was similar to their ranking by topo inhibition in
      vitro rather than by pol inhibition; therefore, topo inhibition might have been
      effecting zygote development inhibition. These results suggested that catechin
      derivatives indeed reached the nuclear DNA where topo inhibition can occur, thus
      causing the observed cellular effects. From these findings, this zygote
      development inhibition assay will be useful as an anti-pregnant agent screening.

PMID- 23121917
TI  - Rho GTPases in platelet function.
AB  - The Rho family of GTP binding proteins, also commonly referred to as the Rho
      GTPases, are master regulators of the platelet cytoskeleton and platelet
      function. These low-molecular-weight or 'small' GTPases act as signaling switches
      in the spatial and temporal transduction, and amplification of signals from
      platelet cell surface receptors to the intracellular signaling pathways that
      drive platelet function. The Rho GTPase family members RhoA, Cdc42 and Rac1 have
      emerged as key regulators in the dynamics of the actin cytoskeleton in platelets
      and play key roles in platelet aggregation, secretion, spreading and thrombus
      formation. Rho GTPase regulators, including GEFs and GAPs and downstream
      effectors, such as the WASPs, formins and PAKs, may also regulate platelet
      activation and function. In this review, we provide an overview of Rho GTPase
      signaling in platelet physiology. Previous studies of Rho GTPases and platelets
      have had a shared history, as platelets have served as an ideal, non-transformed
      cellular model to characterize Rho function. Likewise, recent studies of the cell
      biology of Rho GTPase family members have helped to build an understanding of the
      molecular regulation of platelet function and will continue to do so through the
      further characterization of Rho GTPases as well as Rho GAPs, GEFs, RhoGDIs and
      Rho effectors in actin reorganization and other Rho-driven cellular processes.

PMID- 23121923
TI  - [Survival with ESRD].

PMID- 23121924
TI  - [Access to kidney transplantation].

PMID- 23121925
TI  - [Children and adolescents with ESRD].

PMID- 23121926
TI  - [Population and methods].

PMID- 23121927
TI  - [Flows between treatment modalities of ESRD].

PMID- 23121928
TI  - [Incidence of ESRD in 2010].

PMID- 23121930
TI  - [Prevalence of ESRD in 2010].

PMID- 23121931
TI  - [The network].

PMID- 23121932
TI  - [Baseline characteristics and indicators of support for new dialysis patients in
      2010].

PMID- 23121933
TI  - [Clinical characteristics and indicators of care of dialysis patients].

PMID- 23121934
TI  - Synthesis and evaluation of a series of 3,4,5-trimethoxycinnamic acid derivatives
      as potential antinarcotic agents.
AB  - A series of 3,4,5-trimethoxycinnamic acid derivatives was prepared and evaluated
      for antinarcotic effects on morphine dependence in mice and binding affinities on
      serotonergic receptors. The key synthetic strategies involve generation of
      ketones 6-7, esters 9-12 through condensation reaction, and amides 13-19 via
      coupling reaction using 1
      hydroxybenzotriazole/ethyl(dimethylaminopropryl)carbodiimide system in high
      yield. We found that the naloxone-induced morphine withdrawal syndrome was
      significantly suppressed by new synthetic 3,4,5-trimethoxycinnamic acid
      derivatives (20 mg/kg/day). Most of 3,4,5-trimethoxycinnamic acid derivatives
      were found to have high affinity to 5-HT(1A) receptor. The naloxone-induced
      morphine withdrawal syndrome was attenuated by (+)8-OH-DPAT (0.1 mg/kg/day,
      i.p.), a 5-HT(1A) receptor agonist. In cortical neuronal cells, (+)8-OH-DPAT (1
      MUM) produced an elevation of the pERK 1/2 expression, and the elevated pERK
      levels were inhibited by WAY 100635, a 5-HT(1A) receptor-specific antagonist.
      Interestingly, the pERK levels were increased by the 3,4,5-trimethoxycinnamic
      acid derivatives and the derivatives-mediated changes in pERK levels were blocked
      by the WAY 100635. These results suggested that new synthetic 3,4,5
      trimethoxycinnamic acid derivatives have a potential antinarcotic effect through
      acting as a 5-HT(1A) receptor agonist in mice.

PMID- 23121935
TI  - A comparative study on the chitosan membranes prepared from glycine hydrochloride
      and acetic acid.
AB  - In this study, glycine hydrochloride (Gly.HCl) is confirmed to be a promising
      solvent for dissolving native chitosan and preparing regenerated chitosan
      membrane. As compared with the chitosan membrane prepared from traditional acetic
      acid, the membrane prepared from Gly.HCl by dry technique shows excellent tensile
      strength and initial modulus, i.e. 103.8MPa and 3.2GPa, respectively, which is
      superior to any chitosan membrane and most chitosan blend membranes reported in
      literatures. Besides, scanning electron microscopy (SEM), wide-angle X-ray
      diffraction (WAXD) and Fourier transform infrared spectroscopy (FT-IR) were used
      to visualize the difference between the two kind of regenerated chitosan
      membranes. The SEM results show that the membrane prepared from Gly.HCl by dry
      technique presents a novel structure, which ensures its high tenacity.
      Furthermore, the chitosan microporous membranes were also prepared using PEG as
      porogen.

PMID- 23121936
TI  - Selective sulfation of carrageenans and the influence of sulfate regiochemistry
      on anticoagulant properties.
AB  - Sulfated polysaccharides are recognized for their broad range of biological
      activities, including anticoagulant properties. The positions occupied by the
      sulfate groups are often related to the level of the inherent biological
      activity. Herein the naturally sulfated galactans, kappa-, iota- and theta
      carrageenan, were additionally sulfated by regioselective means. The
      anticoagulant activity of the resulting samples was then studied using the aPTT
      in vitro assay. The influence of sulfate regiochemistry on the anticoagulant
      activity was evaluated. From kappa-carrageenan three rare polysaccharides were
      synthesized, one of them involved a synthetic route with an amphiphilic
      polysaccharide intermediate containing pivaloyl groups. Iota- and theta
      carrageenan were utilized in a selective C6 sulfation at beta-D-Galp units to
      produce different structures comprising trisulfated diads. All the samples were
      characterized by NMR (1D and 2D). The resulting aPPT measurements suggested that
      sulfation at C2 of 3,6-anhydro-alpha-D-Galp and C6 of beta-D-Galp increased the
      anticoagulant activity.

PMID- 23121937
TI  - Acrylic acid grafted guargum-nanosilica membranes for transdermal diclofenac
      delivery.
AB  - Green, hydrophobic device for controlled transdermal release of diclofenac sodium
      was designed from in situ nanosilica/acrylic acid grafted guargum membranes. Best
      grafting condition was assigned and nanocomposites were formed in situ using
      varying proportions of aqueous nanosilica sol. Nanocomposite/drug conjugates were
      formed by bringing down the medium pH from 9.0 to 7.0. The conjugates were
      characterized through infrared and solid state NMR spectroscopy, electron
      microscopy, hydro-swelling, surface contact angle, viscometry and
      biocompatibility. Most balanced property was exhibited by the membrane containing
      1wt% nanosilica. It also had shown the highest encapsulation efficacy vis-a-vis
      slowest release as compared to others during experimentation in a Franz diffusion
      cell.

PMID- 23121938
TI  - Comparison study of TEMPO and phthalimide-N-oxyl (PINO) radicals on oxidation
      efficiency toward cellulose.
AB  - Regenerated cellulose fibers, type viscose, have been oxidized with sodium
      hypochlorite and catalytic amounts of sodium bromide by using two different
      protocols: first, involving the presence of 2,2,6,6-tetramethylpiperidine-1-oxyl
      radical (TEMPO) and second, employing N-hydroxyphthalimide (NHPI). The reactions
      were carried out at room temperature and pH=10.5 for 2.5h. Viscose oxidized
      samples were analyzed and compared in terms of the negative charged groups
      content, as determined by potentiometric titration and methylene blue adsorption,
      morphologies and crystallinities changes, as well as changes in the degree of
      polymerization. The highest content of the carboxylic groups and the best
      preservation of the morphology and molecular weight of the original material have
      been found in the case of using NHPI/anthraquinone as oxidation mediators. TEMPO
      mediated oxidation leads to the highest depolymerization and cause significant
      degradation of the cellulosic material.

PMID- 23121939
TI  - Effects of molecular weight and pyridinium moiety on water-soluble chitosan
      derivatives for mediated gene delivery.
AB  - The aim of this study is to investigate the effects of molecular weight, the
      pyridinium/trimethyl ammonium (Py/Tr) ratio, the nitrogen atoms (N) in the
      methylated N-(3-pyridylmethyl) chitosan chloride (M3-PyMeChC)/the phosphorus
      atoms (P) in DNA (N/P) ratio, and the physicochemical properties of
      nanopolyplexes on transfection efficiency. The water-soluble chitosan derivative,
      M3-PyMeChC, was used as a non-viral vector to deliver pEGFP-C2 into human
      hepatoma (Huh7) cell lines. The results revealed that higher molecular weight M3
      PyMeChC was able to form complexes completely with DNA at lower N/P ratios than
      that with lower molecular weights, which led to higher transfection efficiency.
      Moreover, the M3-PyMeChC with higher Py/Tr ratios showed superior transfection
      efficiency at lower Py/Tr ratios at all N/P ratios studied. The highest
      transfection efficiency for the nanopolyplexes occurred for a molecular weight of
      82kDa at a N/P ratio of 5. The results indicated that the hydrophobic effect of
      pyridinium moiety could enhance gene transfection efficiency, which can be
      attributed to the dissociation of DNA from nanopolyplexes. High Py/Tr ratios in
      nanopolyplexes tended to decrease cytotoxicity due to delocalization of positive
      charge into a pyridine ring while high N/P ratios and molecular weight increased
      cytotoxicity. Our results showed that the vector was able to spread the positive
      charge by delocalizing it into a heterocyclic ring, suggesting to a promising
      approach to mediate higher levels of gene transfection.

PMID- 23121940
TI  - Green synthesis of gold nanoparticles using a glucan of an edible mushroom and
      study of catalytic activity.
AB  - Gold nanoparticles were synthesized by reducing chloroauric acid with a glucan,
      isolated from an edible mushroom Pleurotus florida, cultivar Assam Florida. Here,
      glucan acts as reducing as well as stabilizing agent. The synthesized gold
      nanoparticles were characterized by UV-visible spectroscopy, HR-TEM, XRD, SEM,
      and FT-IR analysis. The results indicated that the size distribution of gold
      nanoparticles (Au NPs) changed with the change in concentration of chloroauric
      acid (HAuCl(4)). The resulting Au NPs-glucan bioconjugates function as an
      efficient heterogeneous catalyst in the reduction of 4-nitrophenol (4-NP) to 4
      aminophenol (4-AP), in the presence of sodium borohydride. The reduction of 4
      nitrophenol with Au NPs-glucan bioconjugates followed pseudo-first-order
      kinetics. The effect of particle size and gold loading on reduction rate of 4-NP
      was studied with Au NPs-glucan bioconjugates prepared with different
      concentrations of HAuCl(4). The synthesis of catalytically active Au NPs using a
      pure mushroom polysaccharide of known structure is reported for the first time.

PMID- 23121941
TI  - Effect of PEG-salt mixture on the gelation temperature and morphology of MC gel
      for sustained delivery of drug.
AB  - Gelation temperature of MC was reduced from 59 degrees C to 54 degrees C with the
      addition of 10% PEG. Sodium tartrate (NaT) and sodium citrate (NaC) were added to
      the MC-PEG solution to further reduce the gelation temperature close to
      physiological temperature. Different techniques were used to measure the gelation
      temperature of all formulations. It was observed that NaC was more effective in
      reducing the gelation temperature of MC-PEG combination than NaT. Environmental
      scanning electron microscopy (ESEM) images of hydrogels containing NaC and NaT
      showed that NaC containing hydrogel having an interconnected microporous
      structure instead of the hollow rod like structure as in the case of NaT
      containing hydrogel. In vitro drug release studies showed that drug release time
      increased from 6 to 9h by only changing the type of salt from NaT to NaC in MC
      PEG combination.

PMID- 23121942
TI  - Development and evaluation of tamarind seed xyloglucan-based mucoadhesive buccal
      films of rizatriptan benzoate.
AB  - Mucoadhesive buccal films were developed using tamarind seed xyloglucan (TSX) as
      novel mucoadhesive polysaccharide polymer for systemic delivery of rizatriptan
      benzoate through buccal route. Formulations were prepared based on 3(2) factorial
      design with concentrations of TSX and carbopol 934P (CP) as independent
      variables. Three dependent variables considered were tensile strength,
      bioadhesion force and drug release. DSC analysis revealed no interaction between
      drug and polymers. Ex vivo diffusion studies were carried out using Franz
      diffusion cell, while bioadhesive properties were evaluated using texture
      analyzer with porcine buccal mucosa as model tissue. Results revealed that
      bilayer film containing 4% (w/v) TSX and 0.5% (w/v) CP in the drug layer and 1%
      (w/v) ethyl cellulose in backing layer demonstrated diffusion of 93.45% through
      the porcine buccal mucosa. Thus, this study suggests that tamarind seed
      polysaccharide can act as a potential mucoadhesive polymer for buccal delivery of
      a highly soluble drug like rizatriptan benzoate.

PMID- 23121943
TI  - Thermal expansion behavior of hydrate paramylon in the low-temperature region.
AB  - The thermal expansion behavior of hydrate paramylon between 100 and 300K has been
      investigated using synchrotron X-ray powder diffraction. The X-ray diffraction
      profile at 300K showed a typical pattern of the hydrate triple helical (1->3)
      beta-d-glucan with a hexagonal unit cell (a=15.782A and c=18.580A). On cooling,
      the hydrate paramylon had converted to a "low-temperature phase" around 270K. On
      passing through the phase transition, the a-axis and c-axis values decreased and
      increased, respectively, and the low-temperature phase at 100K exhibited a
      hexagonal unit cell (a=15.586A and c=18.619A). The phase transition took place
      reversibly. Below the transition point, both the a-axis and c-axis values
      decreased linearly. The thermal expansion coefficients are: alpha(a)=1.50*10(
      5)K(-1), alpha(c)=0.33*10(-5)K(-1), and beta=3.08*10(-5)K(-1).

PMID- 23121944
TI  - TiO2 nanowire and TiO2 nanowire doped Ag-PVP nanocomposite for antimicrobial and
      self-cleaning cotton textile.
AB  - The TiO(2) nanowire (TiO(2) Nw) was successfully prepared via hydrothermal method
      through TiO(2) nanoparticle (TiO(2) Np). TiO(2) Np doped silver and TiO(2) Nw
      doped silver were prepared via photo-reducing Ag(+) ions to Ag metal on the
      TiO(2) Np or TiO(2) Nw surfaces. The prepared nanomaterials were evaluated using
      X-ray (XRD) diffraction pattern, scanning electron microscopy (SEM), and
      transmission electron microscopy (TEM). Bleached untreated cotton fabric and PVP
      treated cotton fabrics were coated with the synthesized nanomaterials using pad
      dry-cure method. Photocatalytic activity of untreated and coated cotton fabrics
      with TiO(2) nanomaterials was investigated through the fabric self cleaning of MB
      dye stains. Also, the PVP finished cotton fabric modified by nanomaterials
      demonstrated antimicrobial activity against Gram positive bacteria, Gram negative
      bacteria and fungi. The mechanical properties of coated cotton fabric (tear
      strength, surface roughness, tensile strength and elongation at break) were
      examined.

PMID- 23121945
TI  - Hydrophilic modification of polyester fabric by applying nanocrystalline
      cellulose containing surface finish.
AB  - In this study, polyethylene terephthalate (PET) fabric was modified by applying a
      hydrophilic surface finishing agent that contains nanocrystalline cellulose
      (NCC). To impart superior hydrophilicity, NCC was further cationically modified
      through quaternization by grafting glycidyl tri-methyl ammonium chloride (GTMAC).
      A textile binder, PrintRite595((r)), was added to the finishing system. The
      surface finish was applied on the fabric using a rolling-drying-curing process.
      The modified fabric was characterized in terms of coating durability, moisture
      regain, and wettability. The durability of the surface finish was tested by six
      repeated washing steps. The surface properties of the fabric changed from
      hydrophobic to hydrophilic after heat treatment with the NCC-containing surface
      finishing agent. The results from the washing fastness, SEM, FTIR, and EDX
      analyses confirmed that the cationic NCC-containing textile surface finish showed
      superior adhesion onto the cationic dyeable (anionic) PET surface over the un
      modified NCC. Furthermore, the cationic textile surface finish was capable of
      withstanding multiple washing cycles.

PMID- 23121946
TI  - Mucoadhesive properties of tamarind-seed polysaccharide/hyaluronic acid mixtures:
      A nuclear magnetic resonance spectroscopy investigation.
AB  - Mixtures of tamarind-seed polysaccharide (TSP) and hyaluronic acid (HA), which
      are employed as artificial tears for ophthalmic applications in the eye dry
      syndrome, were investigated by NMR spectroscopy by analyzing the effect of TSP/HA
      ratio and total concentration on their capability to form stable aggregates with
      enhanced mucoadhesive properties over those of the separate polysaccharides. The
      effect of TSP, HA or TSP/HA mixtures on the affinity of diclofenac sodium salt
      (DS) to mucin (BSM) was ascertained by means of proton selective relaxation rate
      measurements and assumed as the basis to compare polysaccharides mucoadhesive
      properties. The NMR relaxation parameters of pure DS (2mM), binary DS/BSM (5mg/mL
      or 10mg/mL) and ternary DS/BSM/polysaccharide systems (polysaccharide=TSP, HA or
      variable ratios TSP/HA mixtures) were compared in aqueous medium. The
      experimental data demonstrate that the minimum concentration of 1.5mg/mL of each
      polysaccharide is needed to have formation of a stable TSP/HA aggregate endowed
      with NMR detectable mucoadhesive properties and inside which reciprocal
      synergistic interaction occurs.

PMID- 23121947
TI  - Competitive adsorption between sugar beet pectin (SBP) and hydroxypropyl
      methylcellulose (HPMC) at the oil/water interface.
AB  - The emulsification performance, stability and competitive adsorption of two
      natural food emulsifiers, sugar beet pectin (SBP) and hydroxypropyl
      methylcellulose (HPMC) have been investigated. Both can reduce the surface
      tension and emulsify oil in water. However, due to their different structure and
      conformation they operate via different mechanisms. Using 15% middle chain
      triglycerides (MCTs) oil, the amounts of SBP and HPMC adsorbed in emulsions made
      with these individually and in mixtures were determined. The interfacial
      concentration (Gamma) for SBP stabilized emulsion was ~1.25mg/m(2) and for HPMC
      3.5mg/m(2). The higher adsorption of HPMC was due to multilayer adsorption,
      whereas SBP adsorbed as a monolayer. Competitive adsorption between SBP and HPMC
      was also investigated. When the HPMC concentration approached that of adsorbed
      SBP, the effect of HPMC became dominant and at 1.5wt.% controlled the behavior of
      the mixed emulsions, which were then almost independent of SBP. The minor role of
      SBP was mainly to decrease the proportion of large droplets in the emulsion. A
      model to describe the competitive adsorption between SBP and HPMC is proposed.

PMID- 23121948
TI  - Preparation of starch-sodium lignosulfonate graft copolymers via laccase
      catalysis and characterization of antioxidant activity.
AB  - Graft copolymers of waxy maize starch and sodium lignosulfonate (SLS) were
      prepared by Trametes versicolor laccase catalysis in aqueous solution. Amount of
      SLS grafted based on phenol analysis was 0.5% and 1.0% in the absence and
      presence of 1-hydroxybenzotriazole (HBT), respectively. Starch-SLS graft
      copolymers were effective antioxidants as judged by 2,2'-diphenyl-1
      picrylhydrazyl (DPPH) radical scavenging activity. The presence of laccase caused
      a reduction in starch molecular weight although a cross-linked gel fraction was
      also observed when HBT was present. This new method for preparing starch
      chemically modified with phenolic compounds is simple and the resulting
      antioxidant polymers have potential in food, cosmetic and packaging applications.

PMID- 23121949
TI  - Identification and releasing characteristics of high-amylose corn starch
      cinnamaldehyde inclusion complex prepared using ultrasound treatment.
AB  - In this study, the high-amylose corn starch-cinnamaldehyde inclusion complex was
      prepared by an ultrasound treatment and its releasing characteristic was
      investigated. The results showed that the ultrasound treatment (35 degrees C,
      10min and 250W) generated a higher encapsulation rate of 40.2% than the
      conventional treatment (encapsulation rate, 5.7%). Data obtained from Fourier
      transform infrared (FT-IR) spectroscopy and thermogravimetric analysis (TGA)
      indicated that cinnamaldehyde was successfully encapsulated by high-amylose corn
      starch and the encapsulation significantly increased the dissociation temperature
      of cinnamaldehyde by around 70 degrees C. Compared to the physical mixture of
      high-amylose corn starch and cinnamaldehyde, the formed inclusion complex had
      good retention ability and reduced the releasing rate of cinnamaldehyde from
      57.5% to 28.4% in the first week. These results suggest that cinnamaldehyde could
      be encapsulated by high-amylose corn starch with an ultrasound treatment for
      presenting the releasing behavior in food preservation.

PMID- 23121950
TI  - Structural and mechanical characteristics of film using modified corn starch by
      the same two chemical processes used in different sequences.
AB  - Structure of dual modified starches, cross-linked esterified corn starch (CES)
      and esterified cross-linked corn starch (ECS), and product films (CEF and ECF)
      were characterized by Fourier transform infrared (FT-IR) spectroscopy, X-ray
      diffraction and scanning electron microscopy (SEM). The peak 1730cm(-1) of IR
      spectra confirmed the formation of ester carbonyl groups in starch matrix. The
      sequence of modification procedure had an impact on the final modification
      degree, resulting in structural differences of modified starches and starch
      films. Compared to native starch film (NF), CEF and ECF showed improved
      transparence (77.59% and 74.39% respectively) with compact structure, lower
      crystallinity (6.5% and 7.4% respectively). Results of mechanical test indicated
      that structure of ECF was more flexible than CEF, whereas tensile strength was
      higher in CEF. Accordingly, complex modification could be an effective method to
      adequate properties of starch films for specific processing requirements.

PMID- 23121951
TI  - Characterization of the interaction between chitosan and inorganic sodium
      phosphates by means of rheological and optical microscopy studies.
AB  - The physicochemical and rheological properties of chitosan and two different
      inorganic sodium phosphate dispersions (NaH(2)PO(4) and Na(3)PO(4)) were
      investigated in order to elucidate the role of different factors, such as ratios
      between polymer and sodium inorganic phosphates, different pHs and storage
      stability, on the gelling properties of chitosan. This was deemed opportune since
      physico-chemical characterizations of chitosan in the literature often appear
      incomplete and questionable. We also compared the elastic modulus values of the
      different chitosan/inorganic phosphate systems and examined their behaviour
      through optical microscopy analyses. The most efficient formulations that showed
      a thermogelling capacity with a significant gel transition behaviour after 24h
      were the NaH(2)PO(4)/chitosan and Na(3)PO(4)/chitosan systems at ratio 2 and pH
      7.0. These results confirmed the importance of the pH value and ratio selection
      for the final systems.

PMID- 23121952
TI  - Chemical characterization of a water insoluble (1->3)-alpha-D-glucan from an
      alkaline extract of Aspergillus wentii.
AB  - The chemical structure of a water insoluble alpha-glucan isolated from the cell
      wall of Aspergillus wentii was described on the basis of total acid hydrolysis,
      methylation analysis, and 1D and 2D NMR studies (TOCSY, DQF-COSY, NOESY and HSQC)
      as well as other instrumental techniques. It was established that the analyzed
      preparation contained a linear polymer composed almost exclusively of (1->3)
      linked alpha-d-glucose, with a molecular mass of about 850kDa. The polymer was
      divided into subunits separated by a short spacers of (1->4)-linked alpha-d
      glucoses. Each subunit contained about 200 glucose residues.

PMID- 23121953
TI  - Preparation and slowly digestible properties of beta-cyclodextrins (beta-CDs)
      modified starches.
AB  - The beta-cyclodextrin (beta-CD)-, maltosyl-beta-CD (Mal-beta-CD)- and
      hydroxypropyl-beta-CD (HP-beta-CD)-modified rice starches were prepared and their
      slowly digestible properties were estimated. The results showed that beta-CD, Mal
      beta-CD and HP-beta-CD significantly increased the slow digestibility of beta-CDs
      modified starches (P<0.05). The optimum conditions for the modification were
      obtained: amylose, 4.76%; free lipids, 0.24%; beta-CD, Mal-beta-CD and HP-beta
      CD, 3%; water, 80%; and equilibrium temperature, 25 degrees C. The maximum yield
      of slowly digestible starch (SDS) was 52.1% when beta-CD was used as a denaturant
      (beta-CD, 3%; water, 80%; and equilibrium temperature, 25 degrees C). This higher
      SDS yield was probably attributed to the better compatibility of beta-CD and
      starch molecules. Furthermore, beta-CD-, Mal-beta-CD- and HP-beta-CD-modified
      starches generated slowly digestible curves during enzymatic digestion and showed
      the intermediate predicted glycemic indexes (pGI) of 58.7, 69.1 and 70.3,
      respectively. These findings suggest that the beta-CDs-induced modification is
      one of promising techniques for preparing the SDS products in food and
      pharmaceutical industries.

PMID- 23121954
TI  - Development of antimicrobial cotton fabrics using herb loaded nanoparticles.
AB  - In the present work ethanol, methanol, petroleum ether and water extracts of the
      leaves of Ocimum sanctum were screened for their anti-microbial activity by using
      the agar diffusion method. The minimum inhibitory concentration of the extracts
      was also measured. The methanol extracts O. sanctum proved to have the maximum
      antimicrobial effect were loaded inside the sodium alginate chitosan
      nanoparticles by cation induced controlled gelification method and finished on
      cotton fabric by pad dry cure method. The average particle size of the
      nanoparticles was calculated using dynamic light scattering technique. The
      antimicrobial activity of the fabrics was assessed by using the standard AATCC
      technique (AATCC 100). The quantitative tests proved that cotton fabrics finished
      with the methanol extract of O. sanctum loaded nanoparticles possessed remarkable
      antibacterial activities with excellent wash durability. The study revealed that
      the herb encapsulated nanoparticle could act as a biocontrol agent against
      bacteria in fabrics.

PMID- 23121955
TI  - Thiolated xyloglucan: Synthesis, characterization and evaluation as mucoadhesive
      in situ gelling agent.
AB  - The objective of present study was to enhance bioadhesive potential of xyloglucan
      by thiolation. Thiolation of xyloglucan was achieved with esterification with
      thioglycolic acid. Thiolated xyloglucan was characterized by NMR, DSC, and XRD
      analysis. Thiolated xyloglucan was determined to possess 4mmol of thiol groups/g
      of polymer by Ellman's method. Comparative evaluation of mucoadhesive property of
      ondansetron containing in situ gel system of xyloglucan and thiolated xyloglucan
      using sheep nasal mucosa revealed higher ex vivo bioadhesion time of thiolated
      xyloglucan as compared to xyloglucan. Improved mucoadhesive property of thiolated
      xyloglucan over the xyloglucan can be attributed to the formation of disulfide
      bond between mucus and thiolated xyloglucan. Ex vivo permeation study conducted
      using sheep nasal showed improved drug permeation in formulation based on
      thiolated xyloglucan. In conclusion, thiolation of xyloglucan improves its
      bioadhesion and drug permeation without affecting the resultant gel properties.

PMID- 23121956
TI  - Quantitation of 4-O-methylglucuronic acid from plant cell walls.
AB  - The accuracy of commercial alpha-D-glucopyranosyl uronic acid (GlcA) as a
      calibration standard for the determination of the 4-O-methyl-alpha-D
      glucopyranosyl uronic acid (meGlcA) content in plant materials was studied. A
      batch of meGlcA standard was purified from commercial birch xylan and quantified
      using nuclear magnetic resonance spectroscopy. Both commercial GlcA and the
      purified meGlcA were used as standards for the quantitation of meGlcA in
      Arabidopsis thaliana stems, as well as wood and wheat straw samples using acid
      methanolysis and gas chromatography (GC). The GlcA standard was partially
      lactonized during acid methanolysis, thus yielding six glycoside peaks in GC. If
      all six GlcA-derived peaks were included in the GlcA calibration curve, the
      calculated meGlcA content was underestimated by 30% compared with that obtained
      using the purified meGlcA as a standard. The meGlcA content was best estimated by
      including either the two main GlcA peaks or only peaks corresponding to
      pyranosides and furanosides of GlcA in the calibration curve.

PMID- 23121957
TI  - Preparation of amino terminated polyamidoamine functionalized chitosan beads and
      its Cr(VI) uptake studies.
AB  - Chitosan beads, functionalized by amino terminated hyperbranched dendritic
      polyamidoamine (up to 3rd generation) were prepared by Michael addition of methyl
      acrylate to amino groups on the chitosan surface and amidation of terminal ester
      groups by ethylene diamine. All the three generation chitosan beads were used for
      chromium removal along with raw chitosan beads. However, the 3rd generation
      polyamidoamine chitosan beads (3ACB) have been protonated using HCl
      (3ACBP)/loaded with zirconium using ZrOCl(2).8H(2)O (3ACBZr) to enhance the
      sorption capacity towards Cr(VI). The zirconium loaded chitosan beads showed
      higher Cr(VI) sorption than the other modified chitosan beads. The zirconium
      loaded chitosan beads were characterized using SEM, EDAX, FT-IR, XRD, DSC and
      TGA. The system variables studied include agitation time, initial concentration
      of sorbate, pH, co-ions in the medium and temperature on the sorption of
      chromium. The chromium uptake onto 3ACBZr obeys the Freundlich isotherm.
      Thermodynamic studies revealed that the nature of chromium sorption is
      spontaneous and endothermic. The mechanism of chromium sorption onto the sorbent
      was established.

PMID- 23121958
TI  - Improving the mechanical and thermal properties of gelatin hydrogels cross-linked
      by cellulose nanowhiskers.
AB  - This study demonstrates the preparation of a renewable and biocompatible hydrogel
      with superior mechanical properties consisting of a gelatin matrix cross-linked
      with oxidized cellulose nanowhiskers. We found an increased degree of chemical
      cross-linking (0.14-17%) between gelatin and nanowhiskers with the increased
      amount of aldehyde contents (0.062-0.230mmolg(-1)). (1)H nuclear magnetic
      resonance (NMR) T(2) relaxation experiments on D(2)O swollen hydrogels
      demonstrated systems consisting of both gelatin and cellulose nanowhiskers
      displayed a higher percentage of "ridge" protons, attributed in part to
      increasing chemical cross-linking junction points between gelatin and
      nanowhiskers. This increase in hydrogel rigidity not only modified local chain
      dynamics but also influenced gel swelling, showing relatively reduced water
      uptake ability than that of the neat gelatin. Rheological measurements confirmed
      a 150% improvement in storage modulus (G') of the cross-linked hydrogels compared
      to neat gelatin. Chemical cross-linking also increased the resistance of the gels
      towards thermal degradation above the melting temperature of gelatin as observed
      by thermal scanning experiments.

PMID- 23121959
TI  - Evaluation of pretreatment methods for enzymatic saccharification of wheat straw
      for bioethanol production.
AB  - Pretreatment is an essential step in the enzymatic hydrolysis of biomass and
      subsequent production of bioethanol. The current study is focused on two
      different pretreatment methods of wheat straw using mild temperatures (100
      degrees C for 2h and RT for overnight). In one method, native substrate was
      treated with 1.5% (w/v) NaOH at two different above mentioned conditions followed
      by acid hydrolysis (0.75% (v/v) sulfuric acid at 100 degrees C for 2h). In
      another method, the native substrate was initially treated with acid (0.75% (v/v)
      sulfuric acid at 100 degrees C for 2h) followed by treatment with 1.5% (w/v) NaOH
      at two different above conditions. After the pretreatments, the residues were
      treated with Accellerase 1500 (26U/g) and maximum yield of glucose (65.2gL(-1))
      were found with 0.75% sulfuric acid (100 degrees C for 2h) followed by alkali
      (1.5% NaOH at 100 degrees C for 2h). Fermentation of this hydrolyzate using
      Saccharomyces cerevisiae strain produced 24.4gL(-1) of ethanol with corresponding
      yield of 0.44g/g.

PMID- 23121961
TI  - Beetle forewings: Epitome of the optimal design for lightweight composite
      materials.
AB  - Based on studies of the forewings of two beetles, Allomyrina dichotoma and
      Prosopocoilus inclinatus, this paper reviews and identifies the potential
      benefits of studying the structure of the beetle forewing and the associated
      development of lightweight biomimetic composite materials. The forewings of both
      beetle species consist of an integrated border frame structure and a large center
      part with distributed trabecular supports in the hollow core. The forewings of
      the male A. dichotoma are constructed to reflect a lightweight honeycomb design.
      However, the forewings of P. inclinatus are a durable structure. The biological
      significance of these structures is also discussed. This work proposes an
      integrated honeycomb structure inspired by the beetle forewing. A series of
      biological models are also proposed for lightweight integrated honeycomb
      structures and durable sandwich structures with a trabecular core, which are
      intended to establish a new direction in the development of biomimetic composite
      materials.

PMID- 23121960
TI  - Chitosan/alginate complexes for vaginal delivery of chlorhexidine digluconate.
AB  - Chitosan/alginate complexes were prepared at different polycation/polyanion molar
      ratios and freeze-dried vaginal inserts were obtained for chlorhexidine
      digluconate local delivery in genital infections. Complex yield, FT-IR spectra,
      and TGA thermograms were studied to confirm the interaction between the two
      polyions. The influence of different complexes on physical handling, morphology,
      and drug distribution in the samples were evaluated by friability test, scanning
      electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDS),
      respectively. In vitro water-uptake, mucoadhesion and release tests were
      performed as well as microbiological tests toward pathogenic vaginal
      microorganisms. The results showed that the selection of suitable
      chitosan/alginate molar ratio and drug loading allowed modulate insert ability to
      hydrate, adhere to the mucosa, and release chlorhexidine digluconate. The insert
      containing an excess of alginate was found to be the best performing formulation
      and showed good antimicrobial activity toward the pathogens Candida albicans and
      Escherichia coli.

PMID- 23121962
TI  - Extruded films of blended chitosan, low density polyethylene and ethylene acrylic
      acid.
AB  - The obtaining of chitosan extruded films was possible by using low density
      polyethylene (LDPE) as a matrix polymer and ethylene-acrylic acid copolymer as an
      adhesive, in order to ensure adhesion in the interphase of the immiscible
      polymers. The obtained blend films were resistant; however, a reduction in the
      mechanical resistance was observed as chitosan concentration increased. The
      thermal stability of the films showed a certain grade of interaction between
      polymers as seen in FTIR spectra. The antifungal activity of the extruded films
      was assessed against Aspergillus niger and high inhibition percentages were
      observed, which may be mainly attributed to barrier properties of the extruded
      films and the limited oxygen availability, resulting in the inability of the
      fungi to grow. A low adherence of fungal spores to the material surface was
      observed, mainly in areas with chitosan clumps, which can serve as starting
      points for material degradation.

PMID- 23121963
TI  - Inducing surface hydrophobization on cornstarch film by SF6 and HMDSO plasma
      treatment.
AB  - The development of thermoplastic materials based on starch has become a promising
      alternative for reducing plastic waste. To this end, plasma treatments were used
      to enhance the hydrophobicity of cornstarch films. Cornstarch films plasticized
      using glycerol and distilled water were prepared by casting. A surface
      modification method was employed using different precursor gases, HMDSO and
      SF(6), and a combined treatment using HMDSO followed by SF(6) (HMDSO/SF(6)) and
      then the reverse, using SF(6) first followed by HMDSO (SF(6)/HMDSO). The results
      indicated that the induced surface morphology determines the contact angle. It
      was observed that all films became hydrophobic, and films that were initially
      treated with SF(6) showed the greatest hydrophobicity if no further coating was
      applied, or if the treated surface was further coated using HMDSO. Under both of
      these treatment conditions the contact angle was greater than 110 degrees .

PMID- 23121964
TI  - Novel biopolymer gel electrolyte for dye-sensitized solar cell application.
AB  - We report a new biopolymer electrolyte for dye sensitized solar cell application.
      To develop polymer electrolyte, potassium iodide have been added in agarose
      biopolymer matrix and characterized using various techniques like complex
      impedance spectroscopy, Infrared spectroscopy (IR), X-ray diffraction (XRD),
      scanning electron microscopy (SEM). Complex impedance spectroscopy shows many
      folds enhancement in ionic conductivity (sigma) by salt doping and conductivity
      maxima was obtained near 60:40 composition. Infrared spectroscopy confirms the
      formation of composite nature. XRD revels the reduction of crystallinity by salt
      doping as well affirms the composite nature. Scanning electron microscopy (SEM)
      shows reduction in crystallinity of gel matrix by salt doping which is a known
      favorable condition for ionic conductivity enhancement. To further affirm the
      conductivity enhancement in the gel electrolyte system a theoretical hopping
      model is also described in details. A DSSC has been developed using maximum
      electrical conductivity film which shows 0.54% efficiency at 1 sun condition.

PMID- 23121966
TI  - An innovative method for preparation of nanometal hydroxide superabsorbent
      hydrogel.
AB  - A novel method for preparation of a conducting nanometal hydroxide hydrogel was
      undertaken. In situ accommodation of metal hydroxide nanoparticles within swollen
      hydrogel networks is developed. Thus, poly(acrylic acid/acrylate) hydrogel
      (PAAc/AC) was prepared by simultaneous polymerization of acrylic acid/acrylate
      (AAc/AC). Electrodeposition hydroxide of nanoiron and nanocopper into (PAAc/AC)
      hydrogel was performed. Swelling behaviour and swelling kinetics of prepared
      hydrogel were evaluated in media having different pH values. The conductivity of
      both PAAc/AC/nanocopper hydroxide and PAAc/AC/nanoiron hydroxide were measured in
      comparison with that for PAAc/AC hydrogel. An amelioration in conductance of
      PAAc/AC hydrogel having 0.8*10(3)MUS after being incorporated with nanocopper
      hydroxide and nanoiron hydroxide to be 1.5*10(3)MUS and 2.6*10(3)MUS,
      respectively has been achieved. Distribution of the metal hydroxide nanoparticles
      penetrated within the hydrogel networks using transmission electron microscopy
      has been thoroughly elucidated.

PMID- 23121965
TI  - Microwave based synthesis of polymethyl methacrylate grafted sodium alginate: its
      application as flocculant.
AB  - Polymethyl methacrylate grafted sodium alginate (SAG-g-PMMA) was synthesized by
      microwave assisted method. The grafting of the PMMA chains on the polysaccharide
      backbone was confirmed through intrinsic viscosity study, FTIR spectroscopy,
      elemental analysis (C, H, N, O and Na), SEM and TGA study. The intrinsic
      viscosity of sodium alginate appreciably improved on grafting of PMMA chains,
      thus resulting grafted product with potential application as superior
      viscosifier. Further, flocculation efficacy of the graft copolymer was studied in
      coal fine suspension through jar test procedure, toward possible application as
      flocculant.

PMID- 23121967
TI  - Sugar palm (Arenga pinnata): Its fibres, polymers and composites.
AB  - Sugar palm (Arenga pinnata) is a multipurpose palm species from which a variety
      of foods and beverages, timber commodities, biofibres, biopolymers and
      biocomposites can be produced. Recently, it is being used as a source of
      renewable energy in the form of bio-ethanol via fermentation process of the sugar
      palm sap. Although numerous products can be produced from sugar palm, three
      products that are most prominent are palm sugar, fruits and fibres. This paper
      focuses mainly on the significance of fibres as they are highly durable,
      resistant to sea water and because they are available naturally in the form of
      woven fibre they are easy to process. Besides the recent advances in the research
      of sugar palm fibres and their composites, this paper also addresses the
      development of new biodegradable polymer derived from sugar palm starch, and
      presents reviews on fibre surface treatment, product development, and challenges
      and efforts on properties enhancement of sugar palm fibre composites.

PMID- 23121968
TI  - Thermal and mechanical properties of bio-nanocomposites reinforced by Luffa
      cylindrica cellulose nanocrystals.
AB  - Cellulose nanocrystals have been prepared by acid hydrolysis of Luffa cylindrica
      fibers. The acid-resistant residue consisted of rod-like nanoparticles with an
      average length an diameter around 242 and 5.2nm, respectively (aspect ratio
      around 46). These cellulose nanocrystals have been used as a reinforcing phase
      for the processing of bio-nanocomposites using polycaprolactone (PCL) as matrix.
      To promote interfacial filler/matrix interactions the surface of cellulose
      nanocrystals was chemically modified with n-octadecyl isocyanate (C(18)H(37)NCO).
      Evidence of the grafting was supported by infrared spectroscopy and elemental
      analysis. X-ray diffraction analysis was used to confirm the integrity of
      cellulose nanocrystals after chemical modification. Both unmodified and
      chemically modified nanocrystals were used to prepare nanocomposites. The thermal
      properties of these materials were determined from differential scanning
      calorimetry and their mechanical behavior was evaluated in both the linear and
      non-linear range.

PMID- 23121969
TI  - Regulation of Salmonella flagellin-induced interleukin-8 in intestinal epithelial
      cells by muramyl dipeptide.
AB  - Toll-like receptor 5 (TLR5) and nucleotide-binding oligomerization domain 2
      (Nod2) are two important pattern recognition receptors involved in innate
      immunity to invading pathogens. Flagellin, recognized by TLR5, is Salmonella's
      dominant pro-inflammatory determinant in intestinal epithelial cells (IECs). Nod2
      has played a pivotal role in protecting against intestinal bacterial infection.
      Therefore the aim of the study is to investigate regulation of Salmonella
      flagellin-induced interleukin (IL)-8 (IL-8) in IECs by Nod2 agonist, muramyl
      dipeptide (MDP). We found that MDP by itself induced only a weak IL-8 secretion
      in Caco-2 cells. However, it did show synergistic enhancement on flagellin
      induced IL-8 production in Caco-2 cells, possibly caused by flagellin-mediated
      enhanced Nod2 recruitment into cell membrane. By Western blot and siRNA, we
      showed ERK and NF-kappaB, Nod2 and Rip2 were involved in the synergistic effect
      of MDP. These findings suggested that the cooperation of TLR5 and Nod2 in IECs
      regulates inflammatory response to Salmonella infection.

PMID- 23121970
TI  - Mechanisms underlying sCD40 production in hemodialysis patients.
AB  - CD40 and its ligand (CD40L) regulate several cellular functions, including T and
      B-cell activation. The soluble form of CD40 (sCD40) antagonizes CD40/CD40L
      interaction. Patients undergoing hemodialysis (HD) present elevated sCD40 serum
      levels, which underlying molecular mechanisms are unknown. We studied sCD40 serum
      and urinary levels, CD40 membrane and gene expression and membrane shedding in
      HD, uremic not-HD patients (UR) and healthy subjects (N). We found that in HD
      sCD40 serum levels were higher than UR and N, being significantly elevated in
      anuric patients, and that sCD40 correlated to renal function in UR subjects, who
      presented also a reduced sCD40 urinary excretion rate. HD and UR presented
      reduced CD40 membrane and gene expression. The concentration of TNF-alpha
      converting enzyme (TACE), responsible for CD40 cleavage was not different between
      HD and N. Therefore the reduced renal clearance is the main cause of elevated
      sCD40 levels in HD. This finding could have relevant clinical implications.

PMID- 23121971
TI  - Innate-like behavior of human invariant natural killer T cells during herpes
      simplex virus infection.
AB  - Invariant natural killer T (iNKT) cells, CD1d restricted T cells, are involved in
      the immune responses against various infection agents. Here we describe their
      behavior during reactivation of human herpes simplex virus (HSV). iNKT cells
      exhibit only discrete changes, which however, reached statistically significant
      level due to the relatively large patient group. Higher percentage of iNKT cells
      express NKG2D. iNKT cells down-regulate NKG2A in a subset of patients. Finally,
      iNKT cells enhance their capacity to produce TNF-alpha. Our data suggests that
      iNKT cells are involved in the immune response against HSV and contribute mainly
      to its early, innate phase.

PMID- 23121974
TI  - Immune characterization of mesenchymal stem cells in human umbilical cord
      Wharton's jelly and derived cartilage cells.
AB  - Mesenchymal stem cells derived from human umbilical cord Wharton's jelly
      (hWJMSCs) became prospective seed cell candidate for tissue engineering and cell
      based therapy because of its variety source, easy procurement, robust
      proliferation, and high purity compared with bone marrow- and adipose-derived
      MSCs. Such neonatal stem cells can be isolated from a variety of extraembryonic
      tissues and appear to be more primitive and have greater multi-potentiality than
      their adult counterparts. In this study, we investigated the immune characters of
      hWJMSCs and its derived cartilage cells (hWJMSC-Cs) by detecting the expression
      of major histocompatibility complex I/I(MHC-I/II), costimulatory molecules (CD40,
      CD80 and CD86) and immune inhibitors including human leukocyte antigen G (HLA-G),
      indoleamine-2,3-dioxygenase (IDO), and prostaglandin E2 (PGE2). We found that
      hWJMSCs did not express MHC-II and costimulatory molecules, but moderately
      expressed MHC-I, and positively expressed immune inhibitors as HLA-G, IDO, PGE2,
      demonstrating their very low immunogenicity and potential to induce immune
      tolerance microenvironment in hosts. The results of chondrogenic differentiated
      hWJMSCs(hWJMSC-Cs) are similar to those of undifferentiated cells, except for the
      slightly elevated MHC-II and costimulators expression. Additionally, we detected
      cytokine profile of hWJMSCs through cytokine antibody array and verified by
      western blot the positive expression of immune suppression-related molecules,
      HGF, VEGF, TGF, and IL-10. Furthermore, to investigate the in vivo immune
      response of the cells, hWJMSCs-scaffold constructs were implanted into rabbits
      and rats, and the result showed that hWJMSCs did not elicit immune rejection in
      the animals. Their intermediate state between adult and embryonic stem cells
      makes them an ideal candidate for reprogramming to the pluripotent status.
      Additional studies are necessary to clarify the potential of hWJMSCs to be used
      in cartilage and other tissue regeneration and cell-based therapies.

PMID- 23121973
TI  - H(1)R expression by CD11B(+) cells is not required for susceptibility to
      experimental allergic encephalomyelitis.
AB  - The histamine H(1) receptor (Hrh1/H(1)R) was identified as an autoimmune disease
      gene in experimental allergic encephalomyelitis (EAE), the principal autoimmune
      model of multiple sclerosis (MS). Previously, we showed that selective re
      expression of H(1)R by endothelial cells or T cells in H(1)RKO mice significantly
      reduced or complemented EAE severity and cytokine responses, respectively. H(1)R
      regulates innate immune cells, which in turn influences peripheral and central
      nervous system CD4(+) T cell effector responses. Therefore, we selectively re
      expressed H(1)R in CD11b(+) cells of H(1)RKO mice to test the hypothesis that
      H(1)R signaling in these cells contributes to EAE susceptibility. We demonstrate
      that transgenic re-expression of H(1)R by H(1)RKO-CD11b(+) cells neither
      complements EAE susceptibility nor T cell cytokine responses highlighting the
      cell-specific effects of Hrh1 in the pathogenesis of EAE and MS, and the need for
      cell-specific targeting in optimizing therapeutic interventions based on such
      genes.

PMID- 23121975
TI  - A distinct tolerogenic subset of splenic IDO(+)CD11b(+) dendritic cells from
      orally tolerized mice is responsible for induction of systemic immune tolerance
      and suppression of collagen-induced arthritis.
AB  - In oral tolerance, locally instigated tolerance in the gut propagate to systemic
      tolerance. In order to investigate the mechanism, we analyzed indoleamine 2,3
      dioxygenase (IDO) expression in splenic dendritic cell (DC) subsets and tested
      whether DCs suppress collagen-induced arthritis (CIA) by inducing regulatory T
      cells (Tregs). The proportion of IDO-expressing cells was higher in the CD11b(+)
      subset of splenic DCs from orally tolerized CIA mice. These DCs suppressed type
      II collagen-specific T cell proliferation and promoted Treg induction from
      CD4(+)CD25(-) T cells using transforming growth factor-beta. These DCs also
      increased the expression of cytotoxic T lymphocyte antigen-4 and programmed death
      1 on Tregs. When adoptively transferred, spenic IDO-expressing CD11b(+) DCs from
      tolerized animals suppressed the development of arthritis, increased the
      Treg/Th17 cell ratio, and decreased the production of inflammatory cytokines in
      the spleen. Taken together, a distinct subset of splenic IDO(+)CD11b(+)DCs is
      responsible for the systemic immune regulation in oral tolerance.

PMID- 23121972
TI  - Anti-tumor immunity: myeloid leukocytes control the immune landscape.
AB  - The immune surveillance hypothesis proposed over 50 years ago that many
      precancerous lesions are eliminated without a histological trace due to
      immunological pressure. Since then, it has become apparent that both the tumor
      and the anti-cancer immune response evolve over a long period to allow the
      eventual escape of nascent precancerous lesions into full-blown tumors. Although
      primarily focusing on loss of antigenicity, the immunoediting hypothesis has
      gradually evolved to appreciate the role of active immunosuppression in tumor
      progression, where myeloid leukocytes are increasingly recognized as the major
      driving force. This review highlights recent studies implicating how myeloid
      cells with antigen-presenting capabilities are co-opted by tumors to promote
      malignant progression. Because at least some advanced tumors remain significantly
      immunogenic, these new studies add a tweak to the immunoediting hypothesis as
      well as a rationale to block immunosuppressive mechanisms as a first-line
      intervention in cancer patients.

PMID- 23121976
TI  - Cell-mediated immune response to epitopic MAP (multiple antigen peptide)
      construct of LcrV antigen of Yersinia pestis in murine model.
AB  - Yersinia pestis is the causative agent of plague. Cellular immunity seems to play
      an important role in defense against this disease. The subunit vaccine based on V
      (Lcr V) antigen has been proved to be immunogenic in animals and in humans. The
      multiple antigen peptide (MAP), incorporating all the relevant B and T cell
      epitopes is highly immunogenic in mice through intranasal route of immunization
      in PLGA particles containing CpG-ODN as an immunoadjuvant inducing humoral and
      mucosal immune response. In the present study, cell-mediated immune response
      using same MAP was studied in murine model. Primary and memory T cell responses
      were studied in outbred and inbred mice immunized intranasally with MAP in the
      presence of two immunoadjuvants (Murabutide and CpG-ODN). All the three
      compartments (Spleen, Lamina propria and Peyer's patches) of the lymphoid system
      showed increased lymphoproliferative response. Highest lymphoproliferative
      response was observed especially with CpG-ODN. Cytokine profile in the culture
      supernatant showed highest Th(1) and Th(17) levels. FACS analysis showed
      expansion of both CD4(+) and CD8(+) T cells producing gamma-interferon, perforin
      and granzyme-B with major contribution from CD4(+) T cells.

PMID- 23121977
TI  - Molecular mimicry between HSP 65 of Mycobacterium leprae and cytokeratin 10 of
      the host keratin; role in pathogenesis of leprosy.
AB  - Mycobacteria are known to induce autoimmune response in the host. Anti-host
      keratrin antibodies (AkAbs) might be responsible for the autoimmune phenomena in
      leprosy patients as majority of leprosy lesions are manifested in the skin and
      occurrence of keratosis is not an uncommon feature. The aim of this study was to
      find out the level of AkAbs in leprosy patients across the spectrum and to
      explore its correlation with the clinical manifestation of the disease. Further,
      mimicking epitopes of keratin and Mycobacterium leprae components were
      characterized. We screened 140 leprosy patients (27 BT, 28 BL, 41 LL, 25 T1R, 19
      ENL), 74 healthy controls (HC) and 3 psoriasis patients as positive control.
      Highest AkAbs level was observed in the psoriasis patients followed by T1R, LL,
      BL, ENL, TT/BT. AkAbs level was significantly (p<0.05) higher in all the groups
      of leprosy patients except TT/BT in comparison to HC. Significant positive
      correlation was found between number of lesions and level of AkAbs in leprosy
      patients. Highest lympho-proliferation for keratin protein was observed in T1R,
      followed by BL/LL, TT/BT, ENL. Lympho-proliferation was significantly (p<0.05)
      higher in all groups of leprosy patients except ENL in comparison to HC.
      Interestingly, it was noted that hyperimmunization of inbred strains of female
      BALB/c mice and rabbit with M. leprae soluble antigen (MLSA) induce higher level
      of AkAbs. The percentage of FoxP3(+) expressing Treg cells (total
      CD4(+)CD25(+)FoxP3(+) andCD4(+)CD25(+hi)FoxP3(+)) in splenocytes and lymph nodes
      of hyperimmunized mice were declined in comparison to control mice. Further, it
      was found that this autoimmune response can be adoptively transferred in naive
      mice by splenocytes and lymph node cells as well as T cells. Comparative
      molecular characterization between keratin and MLSA noted a cross
      reactivity/similarity between these two antigens. The cross-reactive protein of
      keratin was found to be in molecular weight range ~74-51kDa and at pI 4.5 while
      the cross-reactive protein of MLSA was found to be in molecular weight ~65kDa and
      at pI 4-4.5. Cross-reactive protein of keratin and MLSA was identified and
      characterized by MALDI-TOF/TOF analysis and Mascot software. It was found that
      the keratin (host protein) which reacted with anti-M. leprae sera is cytokeratin
      10 and MLSA which reacted with anti-keratin sera is heat shock protein 65 (HSP
      65). Seven B-cell epitopes of cytokeratin-10 and HSP 65 was found to be similar
      by multiple sequence alignment using ClustalW server and out of which 6 B-cell
      epitopes were found to be on the surface of HSP 65. In conclusion, our study
      provides evidence for the existence of molecular mimicry between cytokeratin-10
      of keratin (host protein) and 65kDa HSP (groEL2) of M. leprae. Presence of
      heightened CMI response of leprosy patients to keratin and positive correlation
      of AkAbs level with number of lesions of leprosy patients showed the clinical
      evidence for its role in the pathogenesis in leprosy.

PMID- 23121978
TI  - Tumor-infiltrating regulatory T cells delineated by upregulation of PD-1 and
      inhibitory receptors.
AB  - Foxp3(+) regulatory T (T(reg)) cells are dominant suppressor cells which regulate
      conventional T (T(conv)) cells. Inside tumor microenvironment, T(reg) cells have
      been known to become potent in suppressing T(conv) cell responses, thereby
      enabling tumor cells to circumvent immune response. However, the underlying
      mechanism by which tumor-infiltrating T(reg) cells display enhanced suppressive
      function is still unresolved. To understand characteristics and function of tumor
      infiltrating T(reg) cells as well as T(conv) cells in the tumor site, we analyzed
      their phenotypes either within tumor burden or at distant site of tumor using
      both heterotopic and orthotopic mouse cancer models. Compared to CD8(+) T cells
      at distant site of tumor, tumor-infiltrating CD8(+) T cells dramatically
      upregulated programmed death 1 (PD-1) and other inhibitory receptors, thereby
      being more exhausted functionally. Tumor-infiltrating CD4(+) T cells also
      expressed higher level of PD-1 than CD4(+) T cells at distant site of tumor but
      very surprisingly, upregulation of PD-1 occurred in CD4(+)Foxp3(+) T(reg) as well
      as CD4(+)Foxp3(-) T(conv) cells. Moreover, tumor infiltrating T(reg) cells
      upregulated other inhibitory receptors such as T cell immunoglobulin mucin 3 (TIM
      3), cytotoxic T lymphocyte antigen-4 (CTLA-4), glucocorticoid-induced tumor
      necrosis factor receptor (GITR), and lymphocyte activation gene-3 (LAG-3). These
      results suggest that upregulation of PD-1 and other inhibitory receptors on tumor
      infiltrating T(reg) cells is related with their enhanced suppressive function.

PMID- 23121979
TI  - N9 microglial cells polarized by LPS and IL4 show differential responses to
      secondary environmental stimuli.
AB  - Microglia participates in the regulation of many inflammation-related
      pathological processes in the central nervous system, but how microglial
      activation is regulated has not been fully understood. Here, by using a
      microglial cell line, we show that microglia, like other macrophages, are
      activated by inflammatory stimuli in a polarized manner. The LPS-polarized M1
      microglia appeared to be unable to respond to a secondary IL4 stimulation, while
      IL4-polarized M2 microglia could respond to secondary LPS stimulation. We also
      show that Notch signaling is involved in microglial polarization. When Notch
      signaling was blocked, the M1 polarization was suppressed, while the M2
      polarization was promoted. Withdraw of the Notch signal inhibitor did not permit
      M2 N9 cells to re-polarize to M1 upon LPS stimulation, suggesting that the
      effects of Notch blockade on microglial polarization could be "memorized" by
      cells. These results suggest complicated mechanisms including epigenetic programs
      in the regulation of macrophage polarization.

PMID- 23121980
TI  - Evaluation of interleukin-23 plasma levels in patients with polycythemia vera and
      essential thrombocythemia.
AB  - Essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis share
      the same acquired genetic lesion, JAK2V617F. It is believed that cytokines
      participate in the activation of JAK2V617F. In this study, we analyzed the plasma
      levels of interleukin (IL)-23, IL-10 and IL-22 in patients with PV and ET. In the
      same subjects we also performed analysis of the JAK2(V617F) mutation, and
      evaluated a possible relationship between interleukin levels and thrombotic
      complications or with the symptom pruritus. Plasma levels of IL-23 were
      significantly increased in all patients with MPN in comparison to controls.
      Moreover, there was a significant difference between the levels of IL-23 in
      patients affected by PV and those measured in controls (8.57+/-3.69pg/mL vs.
      6.55+/-4.125pg/mL; p<0.03). No difference was found between IL-23 levels in ET
      patients and controls. No statistically significant differences were found
      between the levels of IL-23, Il-22 or IL-10 in PV or ET subjects with or without
      thrombosis, in patients with or without pruritus, or according the JAK2V617F
      burden. In PV patients the JAK2 burden and Hb levels correlated with occurrence
      of pruritus. Our study seems to point out a possible involvement of IL-23 in the
      pathogenesis of PV.

PMID- 23121981
TI  - Collagen I enhances functional activities of human monocyte-derived dendritic
      cells via discoidin domain receptor 2.
AB  - We evaluated the involvement of collagen and their discoidin domain receptors
      (DDRs), DDR1 and DDR2, on the activation of human monocyte-derived dendritic
      cells (hDCs). DDR2 was markedly expressed on mature hDCs in comparison to
      immature ones. Collagen I enhanced the release of IL-12p40, TNF-alpha and IFN
      gamma by hDCs. Additionally, hDCs exhibited enhanced expression of costimulatory
      molecules, and potent functional activities which, in turn, has therapeutic
      value. Interestingly, DDR2 depletion showed decrease in capacity of hDCs to
      stimulate T cells proliferation, whereas DDR1 silencing had no significant
      affect. These data demonstrate that DDR2 enhances hDCs activation and contributes
      to their functional activities. In addition, application of collagen I treated
      dendritic cells (DCs) vaccine reduced tumor burden giving longer survival in
      melanoma mice. Our study suggests that collagen I may enhance functional
      activities of DCs in immune response.

PMID- 23121982
TI  - In vivo imaging implicates CCR2(+) monocytes as regulators of neutrophil
      recruitment during arthritis.
AB  - The infiltration of neutrophils and monocytes is a prominent feature of
      inflammatory diseases including human rheumatoid arthritis. Understanding how
      neutrophil recruitment is regulated during pathogenesis is crucial for developing
      anti-inflammatory therapies. We optimized the K/B*N serum-induced mouse arthritis
      model to study neutrophil trafficking dynamics in vivo using two-photon
      microscopy. Arthritogenic serum was injected subcutaneously into one hind footpad
      to induce a local arthritis with robust neutrophil recruitment. Using this
      approach, we showed that the depletion of monocytes with clodronate liposomes
      impaired neutrophil recruitment specifically at the transendothelial migration
      step. The depletion of CCR2(+) monocytes with the monoclonal antibody MC-21
      reproduced these effects, implicating CCR2(+) monocytes as key regulators of
      neutrophil extravasation during arthritis initiation. However, monocyte depletion
      did not prevent neutrophil extravasation in response to bacterial challenge.
      These findings suggest that anti-inflammatory therapies targeting monocytes may
      act in part through antagonizing neutrophil extravasation at sites of aseptic
      inflammation.

PMID- 23121983
TI  - Evidence for cyclic diguanylate as a vaccine adjuvant with novel
      immunostimulatory activities.
AB  - Cyclic diguanylate (c-di-GMP), a bacterial signaling molecule, possesses
      protective immunostimulatory activity in bacterial challenge models. This study
      explored the potential of c-di-GMP as a vaccine adjuvant comparing it with LPS,
      CpG oligonucleotides, and a conventional aluminum salt based adjuvant. In this
      evaluation, c-di-GMP was a more potent activator of both humoral and Th1-like
      immune responses as evidenced by the robust IgG2a antibody response it induced in
      mice and the strong IFN-gamma, TNF-alpha and IP-10 responses, it elicited in mice
      and in vitro in non-human primate peripheral blood mononuclear cells. Further,
      compared to LPS or CpG, c-di-GMP demonstrated a more pronounced ability to induce
      germinal center formation, a hallmark of long-term memory, in immunized mice.
      Together, these data add to the growing body of evidence supporting the utility
      of c-di-GMP as an adjuvant in vaccination for sustained and robust immune
      responses and provide a rationale for further evaluation in appropriate models of
      immunization.

PMID- 23121984
TI  - Arsenic trioxide (As(2)O(3)) induces apoptosis and necrosis mediated cell death
      through mitochondrial membrane potential damage and elevated production of
      reactive oxygen species in PLHC-1 fish cell line.
AB  - Several environmental pollutants, including metals can induce toxicological
      effect on aquatic animal species. Most studies to understand the toxicity of
      arsenic compounds were performed in mammalian cells; however, the study of the
      arsenic toxicity to the aquatic animals' species, including fish, is limited. So
      the objective of this study was first to investigate the effects of As(2)O(3)
      induced toxicity particularly on apoptosis and necrosis mediated cell death in
      fish cell PLHC-1 as compared to the mechanism of toxicity from known mammalian
      cell lines, secondly to relate in vitro effects in fish to those demonstrated by
      in vivo systems. To conduct this study, PLHC-1 cells were exposed to various
      concentrations of As(2)O(3) (0-100 MUM) for 10, 20 and 40 h. The results indicate
      that As(2)O(3) exposure promoted apoptotic and necrotic mediated cell death in a
      concentration and time dependent manner. Cell death (apoptotic and necrotic)
      induced by As(2)O(3) was further confirmed by changes in various phases of cell
      cycle, DNA fragmentation (necro- comet and apo-comet) in the comet assay,
      alteration in mitochondrial membrane potential and formation of increased
      reactive oxygen species (ROS). Apoptotic mediated cell death was confirmed
      further by observing the increased caspase-3 activity and elevated expression of
      p53, cytochrome c and Bax proteins levels in the same experimental conditions.
      PLHC-1 cells were shown to be a good model for evaluating biochemical/cytotoxic
      effects following exposure to various reference chemicals and environmental
      contaminants. In vitro data obtained from this study provides a comprehensive
      approach for the elucidating the actual molecular mechanism for As(2)O(3) induced
      toxicity particularly apoptosis and necrosis mediated cell death in PLHC-1 cell
      line.

PMID- 23121985
TI  - Evaluation of different amendments to stabilize antimony in mining polluted
      soils.
AB  - Soil pollution with antimony is of increasing environmental concern worldwide.
      Measures for its control and to attenuate the risks posed to the ecosystem are
      required. In this study the application of several iron and aluminium oxides and
      oxyhydroxides as soil amendments was evaluated in order to assess their
      feasibility to stabilize Sb in mining polluted soils. Mine soils with different
      pollution levels were amended with either goethite, ferrihydrite or amorphous Al
      oxide at various ratios (0-10%). The effectiveness of such treatments was
      assessed by both batch and column leaching tests. The use of ferrihydrite or
      amorphous Al oxide proved to be highly effective to stabilize Sb. Immobilization
      levels of 100% were found when doses of 5% ferrihydrite or 10% amorphous Al oxide
      were applied, regardless of the soil Sb load. Column leaching studies also showed
      a high Sb leaching reduction (>75%) when soils were amended with 1% ferrihydrite
      or 5% amorphous Al oxide. Moreover, such treatments proved to simultaneously
      immobilize As and Pb in a great extent when soils were also polluted with such
      toxic elements.

PMID- 23121986
TI  - Exploring the potential of applying proteomics for tracking bisphenol A and
      nonylphenol degradation in activated sludge.
AB  - A significant percentage of bisphenol A and nonylphenol removal in municipal
      wastewater treatment plants relies on biodegradation. Nonetheless, incomplete
      information is available concerning their degradation pathways performed by
      microbial communities in activated sludge systems. Hydroquinone dioxygenase
      (HQDO) is a specific degradation marker enzyme, involved in bisphenol A and
      nonylphenol biodegradation, and it can be produced by axenic cultures of the
      bacterium Sphingomonas sp. strain TTNP3. Proteomics, a technique based on the
      analysis of microbial community proteins, was applied to this strain. The
      bacterium proteome map was obtained and a HQDO subunit was successfully
      identified. Additionally, the reliability of the applied proteomics protocol was
      evaluated in activated sludge samples. Proteins belonging to Sphingomonas were
      searched at decreasing biomass ratios, i.e. serially diluting the bacterium in
      activated sludge. The protein patterns were compared and Sphingomonas proteins
      were discriminated against the ones from sludge itself on 2D-gels. The detection
      limit of the applied protocol was defined as 10(-3) g TTNP3 g(-1) total suspended
      solids (TSSs). The results proved that proteomics can be a promising methodology
      to assess the presence of specific enzymes in activated sludge samples, however
      improvements of its sensitivity are still needed.

PMID- 23121987
TI  - Polybrominated diphenyl ethers and their methoxylated and hydroxylated analogs in
      Brown Bullhead (Ameiurus nebulosus) plasma from Lake Ontario.
AB  - Polybrominated diphenyl ethers (PBDEs), methoxylated PBDEs (MeO-PBDEs) and
      hydroxylated PBDEs (OH-PBDEs) were detected and quantified in Brown Bullhead
      (Ameiurus nebulosus) from Lake Ontario. Samples were collected in 2006 from three
      different locations near the city of Toronto: Frenchman's Bay, Toronto Island,
      and Tommy Thompson Park. A total of 117 plasma samples were pooled into 19
      samples, separating males and females by site of capture. Pooled samples were
      analyzed for 36 PBDEs, 20 MeO-PBDEs and 20 OH-PBDEs, but only six PBDEs, five MeO
      and eight OH-compounds were confirmed against standards currently available.
      These peaks were quantified as "identified" peaks, while peaks matching ion
      ratios but not matching the retention time of the available standards were
      quantified as "unidentified" peaks. Both "identified" and "unidentified"
      concentrations were combined to obtain a total concentration. No significant
      variations were obtained for total PBDE concentrations, ranging from 3.33 to 9.02
      ng g(-1)wet weight. However, OH- and MeO-PBDE totals ranged over 1 order of
      magnitude among the samples (not detected - 3.57 ng g(-1)wet weight for OH-PBDEs
      and not detected -0.10 ng/g wet weight for MeO-PBDE). The results of this study
      suggested that these compounds are ubiquitous in biota. Source estimation of MeO-
      and OH-PBDEs in freshwater fish were discussed. Considering that up to date no
      freshwater sources for MeO- or OH-PBDEs have been reported, concentrations found
      should be mainly related to bioaccumulation from anthropogenic sources, although
      other sources could not be dismissed.

PMID- 23121988
TI  - The influence of light exposure, water quality and vegetation on the removal of
      sulfonamides and tetracyclines: a laboratory-scale study.
AB  - The effect of aquatic vegetation (Spyrogira sp. and Zannichellia palustris),
      light exposure and water quality (secondary-treated wastewater vs. ultrapure
      water) on the removal efficiency of six antibiotics (sulfonamides and
      tetracyclines) is studied in laboratory-scale reactors. After 20 d of treatment,
      3-59% of sulfonamides were eliminated in the reactors exposed to light. Removal
      was about 10% in unplanted reactors in darkness. The elimination of tetracycline
      (TC) and oxytetracycline (OTC) ranged between 83% and 97% in both planted and
      unplanted reactors. However, in dark unplanted reactors, OTC was largely removed
      (88%) while only 15% of TC was eliminated. These results suggest that TC was
      mainly removed by photodegradation whereas biodegradation or hydrolysis process
      seems to be significant processes for OTC. Sulfonamides were mainly eliminated by
      biodegradation or indirect photodegradation processes. Pseudo-first order
      kinetics removal rates ranged from 0.003 and 0.007 d(-1) for Sulfamethazine and
      TC in the covered control reactors to 0.13 and 0.21 d(-1) for TC and OTC in the
      uncovered control reactors, with half-lives from 3 to 350 d. A TC
      photodegradation product was tentatively identified in uncovered reactors. This
      study highlights the important role played by light exposure in the elimination
      of antibiotics in polishing ponds.

PMID- 23121989
TI  - Do drug treatment variables predict cognitive performance in multidrug-treated
      opioid-dependent patients? A regression analysis study.
AB  - BACKGROUND: Cognitive deficits and multiple psychoactive drug regimens are both
      common in patients treated for opioid-dependence. Therefore, we examined whether
      the cognitive performance of patients in opioid-substitution treatment (OST) is
      associated with their drug treatment variables. METHODS: Opioid-dependent
      patients (N = 104) who were treated either with buprenorphine or methadone (n =
      52 in both groups) were given attention, working memory, verbal, and visual
      memory tests after they had been a minimum of six months in treatment. Group-wise
      results were analysed by analysis of variance. Predictors of cognitive
      performance were examined by hierarchical regression analysis. RESULTS:
      Buprenorphine-treated patients performed statistically significantly better in a
      simple reaction time test than methadone-treated ones. No other significant
      differences between groups in cognitive performance were found. In each OST drug
      group, approximately 10% of the attention performance could be predicted by drug
      treatment variables. Use of benzodiazepine medication predicted about 10% of
      performance variance in working memory. Treatment with more than one other
      psychoactive drug (than opioid or BZD) and frequent substance abuse during the
      past month predicted about 20% of verbal memory performance. CONCLUSIONS:
      Although this study does not prove a causal relationship between multiple
      prescription drug use and poor cognitive functioning, the results are relevant
      for psychosocial recovery, vocational rehabilitation, and psychological treatment
      of OST patients. Especially for patients with BZD treatment, other treatment
      options should be actively sought.

PMID- 23121990
TI  - Inter-laboratory comparison of turkey in ovo carcinogenicity assessment (IOCA) of
      hepatocarcinogens.
AB  - In three independent laboratories carcinogens (diethylnitrosamine, DEN, 4-(N
      methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone, NNK) and non-carcinogens (N
      nitrosoproline, nicotine) were evaluated in turkey eggs for in ovo
      carcinogenicity assessment (IOCA). Compounds were injected into aseptic
      fertilized eggs. After incubation for 24 days, foci of altered hepatocytes (FAH),
      some with a pseudoglandular structure and/or signs of compression of the
      surrounding tissue were observed in the fetal liver. All laboratories were able
      to distinguish unequivocally the hepatocarcinogen-exposed groups from those
      exposed to non-carcinogens or the vehicle controls, based on the pre-specified
      evaluation parameters: tumor-like lesions, pseudoglandular areas and FAH. In
      addition to focal changes, only the carcinogens induced hepatocellular
      karyomegaly. Lower doses of the carcinogens, which did not induce FAH, were
      sufficient to induce hepatocellular karyomegaly. After exposure to 4 mg DEN, gall
      bladder agenesis was observed in all fetuses. The IOCA may be a valuable tool for
      early investigative studies on carcinogenicity and since it does not use rodents
      may complement chronic rat or mouse bioassays. Test substances that are positive
      in both rodents and fertilized turkey eggs are most probably trans-species
      carcinogens with particular significance for humans. The good concordance
      observed among the three laboratories demonstrates that the IOCA is a reliable
      and robust method.

PMID- 23121991
TI  - Quadrilateral plate fractures of the acetabulum: an update.
AB  - Acetabular fractures with quadrilateral plate involvement form a heterogeneous
      group of fractures, which are not specifically defined by any current
      classification system. Their incidence is increasing due to the rising number of
      elderly osteoporotic fractures. They have always been notoriously difficult
      fractures to treat. We present a systematic review of conservative and operative
      management and their respective outcomes over the last century.

PMID- 23121992
TI  - Comparative ability of comorbidity classification methods for administrative data
      to predict outcomes in patients with chronic obstructive pulmonary disease.
AB  - PURPOSE: Administrative healthcare databases are used for health services
      research, comparative effectiveness studies, and measuring quality of care.
      Adjustment for comorbid illnesses is essential to such studies. Validation of
      methods to account for comorbid illnesses in administrative data for patients
      with chronic obstructive pulmonary disease (COPD) has been limited. Our objective
      was to compare the ability of the Charlson index, the Elixhauser method, and the
      Johns Hopkins' Aggregated Diagnosis Groups (ADGs) to predict outcomes in patients
      with COPD. METHODS: Retrospective cohorts constructed using population-based
      administrative data of patients with incident (n = 216,735) and prevalent (n =
      638,926) COPD in Ontario, Canada, were divided into derivation and validation
      datasets. The primary outcome was all-cause death within 1 year. Secondary
      outcomes included all-cause hospitalization, COPD-specific hospitalization, non
      COPD hospitalization, and COPD exacerbations. RESULTS: In both the incident and
      prevalent COPD cohorts, the three methods had comparable discrimination for
      predicting mortality (c-statistics in the validation sample of incident patients
      of 0.819 for the Charlson method versus 0.822 for the Elixhauser method versus
      0.830 for the ADG method). All three methods had lower predictive accuracy for
      predicting nonfatal outcomes. CONCLUSIONS: In a disease-specific cohort of COPD
      patients, all three methods allowed for accurate prediction of mortality, with
      the Johns Hopkins ADGs having marginally higher discrimination.

PMID- 23121993
TI  - Direct short-term effects of EBP teaching: change in knowledge, not in attitude;
      a cross-cultural comparison among students from European and Asian medical
      schools.
AB  - INTRODUCTION: We report about the direct short-term effects of a Clinical
      Epidemiology and Evidence-based Medicine (CE-EBM) module on the knowledge,
      attitude, and behavior of students in the University Medical Center Utrecht
      (UMCU), Universitas Indonesia (UI), and University of Malaya (UM). METHODS: We
      used an adapted version of a 26-item validated questionnaire, including four
      subscales: knowledge, attitude, behavior, and future use of evidence-based
      practice (EBP). The four components were compared among the students in the three
      medical schools before the module using one-way ANOVA. At the end of the module,
      we measured only knowledge and attitudes. We computed Cronbach's alpha to assess
      the reliability of the responses in our population. To assess the change in
      knowledge and attitudes, we used the paired t-test in the comparison of scores
      before and after the module. RESULTS: In total, 526 students (224 UI, 202 UM, and
      100 UMCU) completed the questionnaires. In the three medical schools, Cronbach's
      alpha for the pre-module total score and the four subscale scores always exceeded
      0.62. UMCU students achieved the highest pre-module scores in all subscales
      compared to UI and UM with the comparison of average (SD) score as the following:
      knowledge 5.04 (0.4) vs. 4.73 (0.69) and 4.24 (0.74), p<0.001; attitude 4.52
      (0.64) vs. 3.85 (0.68) and 3.55 (0.63), p<0.001; behavior 2.62 (0.55) vs. 2.35
      (0.71) and 2.39 (0.92), p=0.016; and future use of EBP 4.32 (0.59) vs. 4.08
      (0.62) and 3.7 (0.71), p<0.01. The CE-EBM module increased the knowledge of the
      UMCU (from average 5.04+/-0.4 to 5.35+/-0.51; p<0.001) and UM students (from
      average 4.24+/-0.74 to 4.53+/-0.72; p<0.001) but not UI. The post-module scores
      for attitude did not change in the three medical schools. CONCLUSION: EBP
      teaching had direct short-term effects on knowledge, not on attitude. Differences
      in pre-module scores are most likely related to differences in the system and
      infrastructure of both medical schools and their curriculum.

PMID- 23121995
TI  - [Using routine information system data to assess maternal and perinatal care
      services in Mali and Senegal (QUARITE trial)].
AB  - BACKGROUND: In sub-Saharan Africa, problems of access to relevant and high
      quality facility-based statistics hinder the assessment of safe motherhood
      programs. The objective of this study was to assess the quality of data collected
      in referral hospitals in Mali and Senegal after the routine information system
      (RIS) was strengthened. METHODS: This was a multicenter observational study
      conducted during the pre-intervention period of a randomized controlled trial
      (trial QUARITE). The RIS was strengthened based on technical, organizational and
      behavioral factors. We included all women who gave birth in the 46 referral
      hospitals from October 1, 2007 to October 30, 2008. The completeness, completion
      and accuracy rates were monitored every 3 months in each hospital. The cost of
      investment needed to strengthen the existing RIS was also determined. RESULTS:
      The mean completeness rate ranged from 94 to 97% depending on the study period.
      The completion and accuracy rates increased during the study period from 72% and
      79% to 87% and 93%, respectively (significant differences). The average
      investment per hospital was less than 1% of state subsidies for public hospitals.
      CONCLUSION: Strengthening the existing information system has set up an
      economically and technologically appropriate system for monitoring maternal and
      perinatal health in Senegal and Mali. We encourage policy makers and researchers
      from countries with limited resources to invest in RIS to improve and monitor the
      performance of health systems.

PMID- 23121994
TI  - A systematic evaluation of laboratory testing for drug-induced immune
      thrombocytopenia.
AB  - BACKGROUND: Drug-induced immune thrombocytopenia (DITP) can be confirmed by the
      demonstration of drug-dependent platelet antibodies in vitro; however, laboratory
      testing is not readily accessible and test methods are not standardized.
      OBJECTIVE: To identify drugs with the strongest evidence for causing DITP based
      on clinical and laboratory criteria. PATIENTS/METHODS: We developed a grading
      system to evaluate the quality of DITP laboratory testing. The 'DITP criteria'
      were: (i) Drug (or metabolite) was required for the reaction in vitro; (ii)
      Immunoglobulin binding was demonstrated; (iii) Two or more laboratories obtained
      positive results; and (iv) Platelets were the target of immunoglobulin binding.
      Laboratory diagnosis of DITP was considered definite when all criteria were met
      and probable when positive results were reported by only one laboratory. Two
      authors applied the DITP criteria to published reports of each drug identified by
      systematic review. Discrepancies were independently adjudicated. RESULTS: Of 153
      drugs that were clinically implicated in thrombocytopenic reactions, 72 (47%)
      were associated with positive laboratory testing. Of those, 16 drugs met criteria
      for a definite laboratory diagnosis of DITP and thus had the highest probability
      of causing DITP. Definite drugs were: quinine, quinidine,
      trimethoprim/sulfamethoxazole, vancomycin, penicillin, rifampin, carbamazepine,
      ceftriaxone, ibuprofen, mirtazapine, oxaliplatin and suramin; the glycoprotein
      IIbIIIa inhibitors abciximab, tirofiban and eptifibatide; and heparin.
      CONCLUSIONS: We identified drugs with the strongest evidence for an association
      with immune thrombocytopenia. This list may be helpful for ranking potential
      causes of thrombocytopenia in a given patient.

PMID- 23121996
TI  - Antigen vehiculization particles based on the Z protein of Junin virus.
AB  - BACKGROUND: Arenavirus matrix protein Z plays an important role in virus budding
      and is able to generate enveloped virus-like-particles (VLPs) in absence of any
      other viral proteins. In these VLPs, Z protein is associated to the plasma
      membrane inner surface by its myristoyl residue. Budding induction and vesicle
      formation properties can be exploited to generate enveloped VLPs platform. These
      structures can be designed to carry specific antigen in the inner side or on the
      surface of VLPs.Vaccines based on VLPs are a highly effective type of subunit
      vaccines that mimic the overall structure of virus particles in absence of viral
      nucleic acid, being noninfectious.In this work we assayed the capacity of Junin Z
      protein to produce VLPs carrying the green fluorescent protein (eGFP), as a model
      antigen. RESULTS: In this report the Junin Z protein ability to produce VLPs from
      293T cells and its capacity to deliver a specific antigen (eGFP) fused to Z was
      evaluated. Confocal microscopy showed a particular membrane bending in cells
      expressing Z and a spot welded distribution in the cytoplasm. VLPs were detected
      by TEM (transmission electron microscopy) and were purified from cell
      supernatant. The proteinase protection assay demonstrated the VLPs integrity and
      the absence of degradation of the fused antigen, thus indicating its internal
      localization. Finally, immunization of mice with purified VLPs produced high
      titres of anti-eGFP antibodies compared to the controls. CONCLUSIONS: It was
      proved that VLPs can be generated from cells transfected with a fusion Junin
      virus Z-eGFP protein in absence of any other viral protein, and the capacity of Z
      protein to support fusions at the C-terminal, without impairing its budding
      activity, allowing vehiculization of specific antigens into VLPs.

PMID- 23121998
TI  - Reticent uneventful rupture of right coronary sinus of valsalva aneurysm into
      right ventricle.
AB  - Aneurysms of sinus of Valsalva are rare congenital or acquired cardiac anomalies.
      They most commonly involve the right or non-coronary sinuses. Herein we report a
      very rare case of a ruptured congenital right sinus of Valsalva aneurysm into the
      right ventricular outflow tract followed conservatively for at least 10 years
      without any events.

PMID- 23121997
TI  - Deep sequencing and expression of microRNAs from early honeybee (Apis mellifera)
      embryos reveals a role in regulating early embryonic patterning.
AB  - BACKGROUND: Recent evidence supports the proposal that the observed diversity of
      animal body plans has been produced through alterations to the complexity of the
      regulatory genome rather than increases in the protein-coding content of a
      genome. One significant form of gene regulation is the contribution made by the
      non-coding content of the genome. Non-coding RNAs play roles in embryonic
      development of animals and these functions might be expected to evolve rapidly.
      Using next-generation sequencing and in situ hybridization, we have examined the
      miRNA content of early honeybee embryos. RESULTS: Through small RNA sequencing we
      found that 28% of known miRNAs are expressed in the early embryo. We also
      identified developmentally expressed microRNAs that are unique to the Apoidea
      clade. Examination of expression patterns implied these miRNAs have roles in
      patterning the anterior-posterior and dorso-ventral axes as well as the
      extraembryonic membranes. Knockdown of Dicer, a key component of miRNA
      processing, confirmed that miRNAs are likely to have a role in patterning these
      tissues. CONCLUSIONS: Examination of the expression patterns of novel miRNAs,
      some unique to the Apis group, indicated that they are likely to play a role in
      early honeybee development. Known miRNAs that are deeply conserved in animal
      phyla display differences in expression pattern between honeybee and Drosophila,
      particularly at early stages of development. This may indicate miRNAs play a
      rapidly evolving role in regulating developmental pathways, most likely through
      changes to the way their expression is regulated.

PMID- 23121999
TI  - Adrenomedullin attenuates vascular calcification in fructose-induced insulin
      resistance rats.
AB  - AIM: To determine the therapeutic effects of adrenomedullin (ADM) on vascular
      calcification and related molecular mechanism in fructose-induced insulin
      resistance rats. METHODS: Rats received ordinary drinking water or 10% fructose
      in drinking water for 12 weeks and subcutaneous injection of normal saline or ADM
      (3.6 MUg kg(-1) ) twice a day for the last 4 weeks. Levels of ADM, calcitonin
      receptor-like receptors (CRLR), receptor activity-modifying proteins (RAMP) as
      well as calcium content, alkaline phosphatase (ALP) activity, osteoblastic and
      contractile smooth muscle markers in aortic media were measured. RESULTS: The
      levels of ADM, CRLR, RAMP2 and RAMP3 in aortic media were increased in fructose
      fed rats. ADM treatment attenuated the fructose-induced insulin resistance,
      increased blood pressure, fasting glucose, insulin, triglycerides and cholesterol
      levels. It improved VSMCs proliferation and disordered arrangement and
      hyperplasia of elastic fibres in fructose-fed rats. Calcium deposits, calcium
      content and ALP activity in the aortic media were increased in fructose-fed rats,
      which were attenuated by ADM treatment. The osteoblastic markers such as
      osteopontin (OPN), bone morphogenetic protein 2 (BMP2) proteins and core binding
      factor alpha-1 (Cbfalpha-1) protein and mRNA expressions were increased in
      fructose-fed rats. ADM treatment increased the OPN protein expression, but
      reduced the BMP2 protein, Cbfalpha-1 protein and mRNA expression. Contractile
      smooth muscle markers such as alpha-actin and smooth muscle 22alpha (SM-22alpha)
      were downregulated in fructose-fed rats, which were recovered by ADM treatment.
      CONCLUSION: Administration of ADM attenuates insulin resistance, calcium
      deposition and osteogenic transdifferentiation in aortic media in fructose-fed
      rats.

PMID- 23122000
TI  - Net benefits: assessing the effectiveness of clinical networks in Australia
      through qualitative methods.
AB  - BACKGROUND: In the 21st century, government and industry are supplementing
      hierarchical, bureaucratic forms of organization with network forms, compatible
      with principles of devolved governance and decentralization of services. Clinical
      networks are employed as a key health policy approach to engage clinicians in
      improving patient care in Australia. With significant investment in such networks
      in Australia and internationally, it is important to assess their effectiveness
      and sustainability as implementation mechanisms. METHODS: In two purposively
      selected, musculoskeletal clinical networks, members and stakeholders were
      interviewed to ascertain their perceptions regarding key factors relating to
      network effectiveness and sustainability. We adopted a three-level approach to
      evaluating network effectiveness: at the community, network, and member levels,
      across the network lifecycle. RESULTS: Both networks studied are advisory
      networks displaying characteristics of the 'enclave' type of non-hierarchical
      network. They are hybrids of the mandated and natural network forms. In the short
      term, at member level, both networks were striving to create connectivity and
      collaboration of members. Over the short to medium term, at network level, both
      networks applied multi-disciplinary engagement in successfully developing models
      of care as key outputs, and disseminating information to stakeholders. In the
      long term, at both community and network levels, stakeholders would measure
      effectiveness by the broader statewide influence of the network in changing and
      improving practice. At community level, in the long term, stakeholders
      acknowledged both networks had raised the profile, and provided a 'voice' for
      musculoskeletal conditions, evidencing some progress with implementation of the
      network mission while pursuing additional implementation strategies. CONCLUSIONS:
      This research sheds light on stakeholders' perceptions of assessing clinical
      network effectiveness at community, network, and member levels during the
      network's timeline, and on the role of networks and their contribution. Overall,
      stakeholders reported positive momentum and useful progress in network growth and
      development, and saw their networks as providing valuable mechanisms for meeting
      instrumental goals and pursuing collaborative interests. Network forms can prove
      their utility in addressing 'wicked problems,' and these Australian clinical
      networks present a practical approach to the difficult issue of clinician
      engagement in state-level implementation of best practice for improving patient
      care and outcomes.

PMID- 23122001
TI  - Oral tissue engineering and implants.

PMID- 23122002
TI  - Editorial: New trends in neurogeometrical approaches to the brain and mind
      problem.

PMID- 23122003
TI  - Correlation between nasal eosinophils and nasal airflows in children with asthma
      and/or rhinitis monosensitised to house dust mites.
AB  - BACKGROUND: Allergic rhinitis and asthma due to mite sensitisation are diseases
      which are frequently associated and characterised by persistent inflammation. In
      the present study, we aimed to investigate the relationship between nasal
      airflows and nasal eosinophils in patients with asthma and/or rhinitis due to
      house dust mite sensitisation. METHODS: Twenty-four children with both rhinitis
      and asthma (R+A), 13 children with rhinitis and no asthma (R) and 10 non-allergic
      healthy children were evaluated prospectively. The patients belonging to the
      first two groups had moderate-severe grade of nasal obstruction. Total nasal
      symptom scores, peak nasal inspiratory flows (PNIFs) obtained by anterior
      rhinomanometry, skin prick tests, nasal eosinophils and FEV1 values were all
      assessed. RESULTS: Percentages of nasal eosinophils and PNIFs in patients with
      R+A and R (r=-0.415, p=0.04) were found to be statistically significant and to
      have an inverse correlation. Skin prick tests were also significantly correlated
      with nasal eosinophils and PNIFs (r=0.372, p=0.01 and r=-0.306, p=0.04,
      respectively). Both PNIFs and nasal eosinophils of patients with R+A were
      significantly correlated with FEV1 values (r=-0.641, p=0.001 and r=0.548,
      p=0.007, respectively). CONCLUSION: In this study, a close relationship was
      demonstrated between eosinophil infiltration and nasal airflows in children
      having asthma and/or rhinitis monosensitised to mites. Additionally, the
      significant association found between FEV1 values and nasal eosinophils or PNIFs
      supported the close link of upper and lower airways.

PMID- 23122004
TI  - Diagnostic utility of a single-epitope sandwich B-type natriuretic peptide assay
      in stable coronary artery disease: data from the Akershus Cardiac Examination
      (ACE) 1 Study.

PMID- 23122005
TI  - Intercepting a moving traffic gap while avoiding collision with lead and trail
      vehicles: gap-related and boundary-related influences on drivers' speed
      regulations during approach to an intersection.
AB  - Using a fixed-base driving simulator, 15 participants actively drove their
      vehicle across a rural road toward an intersection. Their task was to safely
      cross the intersection, passing through a gap in the train of incoming traffic.
      Spatiotemporal task constraints were manipulated by varying the initial
      conditions (offsets) with respect to the time of arrival of the traffic gap at
      the intersection. Orthogonally manipulating the motion characteristics of the
      lead and trail vehicles forming the traffic gap allowed evaluating the influences
      of the global (gap-related) and local (lead/trail-vehicle-related) aspects of the
      inter-vehicular interval. The results revealed that the different initial offsets
      gave rise to functional, continuous and gradual adjustments in approach speed,
      initiated early on during approach to the intersection. Drivers systematically
      accelerated during the final stages of approach, on average crossing the gap
      slightly ahead of the center of the traffic gap. A special-purpose ANOVA
      demonstrated an influence of (global) gap characteristics such as gap size and
      speed. Further analyses demonstrated that the motion characteristics of the lead
      vehicle exerted a stronger influence on approach behavior than the motion
      characteristics of the trail vehicle. The results are interpreted as signing the
      online regulation of approach speed, concurrently based on intercepting the
      (center of the) traffic gap and avoiding collision with the lead and trail
      vehicles.

PMID- 23122006
TI  - A confocal-based morphometric analysis shows a functional crosstalk between the
      actin filament system and microtubules in thrombin-stimulated platelets.

PMID- 23122007
TI  - Mutualism with sea anemones triggered the adaptive radiation of clownfishes.
AB  - BACKGROUND: Adaptive radiation is the process by which a single ancestral species
      diversifies into many descendants adapted to exploit a wide range of habitats.
      The appearance of ecological opportunities, or the colonisation or adaptation to
      novel ecological resources, has been documented to promote adaptive radiation in
      many classic examples. Mutualistic interactions allow species to access resources
      untapped by competitors, but evidence shows that the effect of mutualism on
      species diversification can greatly vary among mutualistic systems. Here, we test
      whether the development of obligate mutualism with sea anemones allowed the
      clownfishes to radiate adaptively across the Indian and western Pacific oceans
      reef habitats. RESULTS: We show that clownfishes morphological characters are
      linked with ecological niches associated with the sea anemones. This pattern is
      consistent with the ecological speciation hypothesis. Furthermore, the
      clownfishes show an increase in the rate of species diversification as well as
      rate of morphological evolution compared to their closest relatives without
      anemone mutualistic associations. CONCLUSIONS: The effect of mutualism on species
      diversification has only been studied in a limited number of groups. We present a
      case of adaptive radiation where mutualistic interaction is the likely key
      innovation, providing new insights into the mechanisms involved in the buildup of
      biodiversity. Due to a lack of barriers to dispersal, ecological speciation is
      rare in marine environments. Particular life-history characteristics of
      clownfishes likely reinforced reproductive isolation between populations,
      allowing rapid species diversification.

PMID- 23122008
TI  - Interleukin-23 and interleukin-17: importance in pathogenesis and therapy of
      psoriasis.
AB  - Emerging data in mice and humans reveals a critical contribution of Th17
      associated cytokines, particularly interleukin-(IL)-23 and IL-17, in the
      pathogenesis of psoriasis. The IL-23/Th17 pathway is a therapeutic target for
      biologic agents and systemic therapies in psoriasis treatment. A literature
      search was performed to review and summarize the current evidence on IL-17 and IL
      23 as a basis for understanding the use of anti-IL-17 and anti-IL-23 agents for
      psoriasis therapy. Using PubMed, recent articles were identified pertaining to IL
      17, IL-23, and psoriasis. Signaling via the heterodimeric IL-23 receptor induces
      production of IL-17, which stimulates production of proinflammatory keratinocyte
      cytokines that mediate the psoriatic response. An overexpression of IL-23, IL-17,
      or Th17 cells in transgenic mice is associated with the development of
      inflammatory disease. Both IL-17 knockout mice and humans with a genetic IL-17
      deficiency are susceptible to extracellular and intracellular pathogens. This
      suggests a potential for adverse effects from clinical administration of anti IL
      23-p40/IL-17 therapies. Anti-p40 antibodies, briakinumab and ustekinumab, were
      tolerated in clinical trials and substantially improved psoriasis. Further trials
      of anti IL-17 therapies are needed to assess their clinical use and potential for
      infection and other adverse events.

PMID- 23122009
TI  - Congenital self-healing reticulohistiocytosis: concern for a poor prognosis.
AB  - Congenital self-healing reticulohistiocytosis (CSHRH) is a rare type of
      Langerhans cell histiocytosis with potential for relapse and systemic
      involvement. Whereas CSHRH was traditionally considered a benign disease, there
      is an approximately 3 percent risk of mortality and a 10 percent chance of
      relapse. This article, using an extensive review of cases since Hashimoto and
      Pritzker first described the condition in 1973, highlights the various
      presentations of CSHRH and reveals high rates of relapse and systemic involvement
      in cases that specifically address features of CSHRH occurring within the first
      year of life. The findings from this review will highlight the importance of
      considering LCH in the differential diagnosis when evaluating a neonate with
      congenital skin eruptions. Timely diagnosis of CSHRH and treatment of systemic
      involvement may decrease the likelihood of adverse outcomes. These patients may
      require closer follow-up and monitoring than previously recommended, especially
      in the first year of life when relapses and systemic involvement occur most
      frequently.

PMID- 23122010
TI  - Facial chromoblastomycosis in sub-Himalayan region misdiagnosed as cutaneous
      leishmaniasis: brief report and review of Indian literature.
AB  - Cases of chromoblastomycosis, although not uncommon, have rarely been reported in
      the literature from our region. These are usually misdiagnosed as cases of
      cutaneous leishmaniasis because we reside in an endemic region for this disease.
      We present herein patients with facial chromoblastomycosis. They were treated
      with long-term sodium stibogluconate, but showed no response to therapy. A biopsy
      revealed these to be cases of chromoblastomycosis, after which the patients were
      started on antifungal agents. There was marked improvement after the correct
      treatment was initiated.

PMID- 23122011
TI  - Disseminated Lyme borreliosis preceded by hepatitis in an African American male.
AB  - Lyme disease is the most common tick-borne disease in the United States and has a
      multitude of systemic effects. Infrequently, however, Lyme disease is seen to
      cause liver dysfunction. Dermatologists should be aware that early, disseminated
      borreliosis can present with multiple erythema migrans plaques and hepatitis.

PMID- 23122012
TI  - Primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma: transformation
      from indolent to aggressive phase in association with CCR7-positive conversion.
AB  - We report a case of primary cutaneous aggressive epidermotropic CD8+ T-cell
      lymphoma that transformed from the indolent phase to the aggressive phase. In the
      aggressive phase, the patient developed numerous subcutaneous lesions on the
      trunk, limbs, and face. The involvement of muscle, right testis, and pharynx were
      also found. We immunohistochemically analyzed the expression of chemokine
      receptors, before and after the transformation of aggressive epidermotropic CD8+
      T-cell lymphoma. The transformation was accompanied by positive conversion of
      CCR7. CCR7 is crucial in lymphatic cell migration and chemotaxis to lymph nodes.
      Therefore, its expression is likely associated with the disseminated behavior of
      T-cell lymphoma.

PMID- 23122013
TI  - Eosinophilic pustular folliculitis in infancy: report of a new case.
AB  - We report a new case of eosinophilic pustular folliculitis in a 23-month-old boy.
      He presented with a seven-month history of recurrent episodes of pustular lesions
      on the scalp after having been treated with oral antifungal and topic antibiotics
      without response. The diagnosis was based on the clinical course and typical
      histopathological findings. Eosinophilic pustular folliculitis in infancy is an
      idiopathic and rare inflammatory disease characterized by recurrent crops of
      sterile pustules involving mainly the scalp. Because it is a benign, self
      limiting condition an accurate diagnosis is essential to avoid unnecessary
      therapies.

PMID- 23122014
TI  - Ulcerated plaques in the pelvic region of an adult female.
AB  - Cutaneous metastatic mammary carcinoma may occur in patients with a history of
      breast carcinoma. Cutaneous metastases typically present as firm papulonodules on
      the chest. We describe a rare case of cutaneous metastatic mammary carcinoma
      arising in a 45-year-old woman presenting as painful, indurated plaques with
      ulceration in the pelvic region.

PMID- 23122015
TI  - Dermoscopy of black-spot poison ivy.
AB  - Black-spot poison ivy is an uncommon presentation of poison ivy (Toxicodendron)
      allergic contact dermatitis. A 78-year-old sought evaluation of a black spot
      present on her right hand amid pruritic vesicles. The presentation of a black
      spot on the skin in a clinical context suggesting poison ivy is indicative of
      black-spot poison ivy. Dermoscopy revealed a jagged, centrally homogeneous, dark
      brown lesion with a red rim. A skin sample was obtained and compared against a
      poison ivy standard using ultra-fast liquid chromatography-tandem mass
      spectrometry (UFLC-MS/MS). This finding confirmed the presence of multiple
      urushiol congeners in the skin sample. Black-spot poison ivy may be added to the
      list of diagnoses that show a specific dermoscopic pattern.

PMID- 23122016
TI  - Fatal Henoch-Schonlein purpura in an adult related to bowel perforation: report
      and review of the literature.
AB  - BACKGROUND: Henoch-Schonlein purpura is an idiopathic, IgA associated, systemic
      small-vessel vasculitis characterized by the clinical tetrad of palpable purpura,
      arthralgias, renal dysfunction, and abdominal pain. Whereas Henoch-Schonlein is
      an overwhelmingly pediatric disease, its rare diagnosis in adults carries a much
      higher morbidity and mortality. OBSERVATIONS: We describe a 52-year-old man with
      biopsy proven Henoch-Schonlein who expired from bowel perforation. CONCLUSIONS:
      Severe gastrointestinal complications and death from gastrointestinal involvement
      by Henoch-Schonlein purpura is rare. The authors surmise that multiple co
      morbidities may have contributed to our patient's demise.

PMID- 23122017
TI  - Oral pemphigus vegetans: a case report.
AB  - Pemphigus is a rare vesiculobullous autoimmune disease that exhibits blistering
      of the skin and oral cavity. It is caused by autoantibodies directed against
      antigens on the surface of keratinocytes. All forms of pemphigus are associated
      with the presence of circulating and skin-fixed autoantibodies. Pemphigus
      vegetans is a rare clinical variant of pemphigus vulgaris and comprises up to 5
      percent of all pemphigus cases. In the following we present the oral presentation
      of pemphigus vegetans. We describe a 33-year-old man who was referred to our
      clinic complaining about mouth sores, tooth pain, and multiple pustules. During
      clinical exam we were able to recognize multiple pustules, ulcerated areas on the
      gingiva, and whitish mucosal plaques. Clinical, histopathological, and direct
      immunofluorescence findings were compatible with pemphigus vegetans.

PMID- 23122018
TI  - An inflammatory verrucous epidermal nevus concomitant with psoriasis: treatment
      with adalimumab.
AB  - A 42-year-old-man presented with generalized inflammatory linear verrucous
      epidermal nevus with concomitant psoriasis vulgaris. Because of unresponsiveness
      of the conventional treatment, we considered treatment with adalimumab.
      Adalimumab was well tolerated and no side effects were observed. Adalimumab has a
      limited effect in treating ILVEN lesions. However, it was effective in treating
      the psoriasis and pruritus related to ILVEN. For these reasons adalimumab can be
      used in treatment of ILVEN concomitant with psoriasis.

PMID- 23122019
TI  - Unknown: a congenital nodule on the scapula.
AB  - We present a new case of a cutaneous bronchogenic cyst on the scapular area in a
      2-year-old boy. The asymptomatic nodule over his right scapula had been detected
      at birth and had been gradually growing. Cutaneous bronchogenic cysts located
      near the scapula are extremely rare. The proposed mechanism is that the accessory
      buds from the tracheobronchial tree/primitive foregut migrated from the thorax in
      an aberrant manner to lie in a periscapular position. Cutaneous bronchogenic
      cysts are poorly recognized by clinicians because they lack pathognomonic
      clinical symptoms. The diagnosis is based on the histopathological findings in
      the majority of cases. Complete excision and histological examination are
      indicated to confirm the diagnosis, to relieve symptoms, and to prevent
      complications, such as infection or malignancy.

PMID- 23122020
TI  - Isolated single digit Porokeratosis of Mibelli: an unusual case.
AB  - Porokeratosis of Mibelli is an uncommon dermatosis, which may be associated with
      immunosuppression and which may undergo malignant transformation. We report a
      patient with a chronic history of a skin lesion of his right 5th finger that was
      histologically confirmed to be Porokeratosis of Mibelli. Although it commonly
      affects the extremities, the isolated involvement of an individual digit of the
      hand has not been previously reported.

PMID- 23122021
TI  - Clear cell acanthoma induced by a dermatofibroma.
AB  - Dermatofibromas are known to induce overlying skin changes and secondary lesions
      including seborrheic keratoses, Bowen disease, and basal cell hyperpigmentation.
      However, a paucity of literature describes clear cell acanthomas being induced by
      a dermatofibromas. We describe an unusual case of a clear cell acanthoma
      overlying a dermatofibroma and present the first dermoscopic image (to our
      knowledge) to the literature.

PMID- 23122022
TI  - Caution advised in interpretation of US FDA risk classification for
      dermatological medications during pregnancy.
AB  - Prescription and non-prescription medications are frequently used by women of
      childbearing age. As many as 40 to 80 percent of women receive at least one
      prescription drug during pregnancy. It is essential to understand the potential
      teratogenicity of medications and offer pregnant women appropriate counseling.
      Available classification references include the Swedish Catalogue of Approved
      Drugs, the US Food and Drug Administration, the Australian system, and the
      Evidence-Based Medicine system.

PMID- 23122023
TI  - Vascular malformation of the glans penis successfully treated with Nd:YAG laser.
AB  - Penile venous malformations are uncommon and those located on the glans are even
      rarer. Treatment of venous malformations of the glans is currently controversial.
      Neodynium (Nd):YAG laser treatment may be a useful option.

PMID- 23122024
TI  - Effective noise estimation and filtering from correlated multiple-coil MR data.
AB  - Modern magnetic resonance (MR) imaging protocols based on multiple-coil
      acquisitions have carried on a new attention to noise and signal statistical
      modeling, as long as most of the existing techniques for data processing are
      model based. In particular, nonaccelerated multiple-coil and GeneRalized
      Autocalibrated Partially Parallel Acquisitions (GRAPPA) have brought noncentral
      chi (nc-chi) statistics into stake as a suitable substitute for traditional
      Rician distributions. However, this model is only valid when the signals received
      by each coil are roughly uncorrelated. The recent literature on this topic
      suggests that this is often not the case, so nc-chi statistics are in principle
      not adequate. Fortunately, such model can be adapted through the definition of a
      set of effective parameters, namely, an effective noise power (greater than the
      actual power of thermal noise in the Radio Frequency receiver) and an effective
      number of coils (smaller than the actual number of RF receiving coils in the
      system). The implications of these artifacts in practical algorithms have not
      been discussed elsewhere. In the present paper, we aim to study their actual
      impact and suggest practical rules to cope with them. We define the main noise
      parameters in this context, introducing a new expression for the effective
      variance of noise which is of capital importance for the two image processing
      problems studied: first, we propose a new method to estimate the effective
      variance of noise from the composite magnitude signal of MR data when
      correlations are assumed. Second, we adapt several model-based image denoising
      techniques to the correlated case using the noise estimation techniques proposed.
      We show, through a number of experiments with synthetic, phantom, and in vivo
      data, that neglecting the correlated nature of noise in multiple-coil systems
      implies important errors even in the simplest cases. At the same time, the proper
      statistical characterization of noise through effective parameters drives to
      improved accuracy (both qualitatively and quantitatively) for both of the
      problems studied.

PMID- 23122025
TI  - What contributes to abuse in health care? A grounded theory of female patients'
      stories.
AB  - BACKGROUND: In Sweden, 20% of female patients have reported lifetime experiences
      of abuse in any health care setting. Corresponding prevalence among male patients
      is estimated to be 8%. Many patients report that they currently suffer from these
      experiences. Few empirical studies have been conducted to understand what
      contributes to the occurrence of abuse in health care. OBJECTIVES: To understand
      what factors contribute to female patients' experiences of abuse in health care.
      DESIGN: Constructivist grounded theory approach. SETTINGS: Women's clinic at a
      county hospital in the south of Sweden. PARTICIPANTS: Twelve female patients who
      all had reported experiences of abuse in health care in an earlier questionnaire
      study. METHODS: In-depth interviews. RESULTS: The analysis resulted in the core
      category, the patient loses power struggles, building on four categories: the
      patient's vulnerability, the patient's competence, staff's use of domination
      techniques, and structural limitations. Participants described how their
      sensitivity and dependency could make them vulnerable to staff's domination
      techniques. The participants' claim for power and the protection of their
      autonomy, through their competence as patients, could catalyze power struggles.
      CONCLUSIONS: Central to the participants' stories was that their experiences of
      abuse in health care were preceded by lost power struggles, mainly through
      staff's use of domination techniques. For staff it could be important to become
      aware of the existence and consequences of such domination techniques. The
      results indicate a need for a clinical climate in which patients are allowed to
      use their competence.

PMID- 23122026
TI  - Relationship between intraocular pressure and glaucoma onset and progression.
AB  - Open-angle glaucoma is a multifactorial disease, and among the several risk
      factors, a high intraocular pressure represents the most consistent and the only
      one that can be modified in order to provide a significant impact over the course
      of the disease. High intraocular pressure is significantly associated to the
      onset and the progression of open angle glaucoma, and the results of several
      randomised controlled clinical trials have consistently attributed a higher 10%
      higher risk for both the development and the progression of the disease to each
      higher single mmHg. Intraocular pressure has been studied in terms of mean value
      and short-term and long-term fluctuations. As of today the mean value represents
      the most significant factor whereas the importance of both short-term and long
      term fluctuations is still debated.

PMID- 23122027
TI  - Retraction: In vitro antioxidant and anticancer activity of young Zingiber
      officinale against human breast carcinoma cell lines.

PMID- 23122029
TI  - Desferrioxamine-cadmium as a 'Trojan horse' for the delivery of Cd to bacteria
      and fungi.
AB  - Molecules naturally designed for the acquisition of essential metals can be used
      as a shuttle to deliver toxic metal ions to target organisms. In this study, we
      describe for the first time the synthesis of a derivative of cadmium and
      desferrioxamine B, a bacterial siderophore. The new compound was characterized by
      elemental analysis, vibrational (infrared and Raman) spectroscopy, mass coupled
      thermal analyses and X-ray diffraction methods. Studies on the in vitro toxicity
      toward a fungus and two bacterial strains indicated that the coordination
      compound is more active against microrganisms than cadmium chloride on a Cd
      concentration basis, indicating that desferrioxamine can work as a "Trojan horse"
      in the delivery of a toxic metal.

PMID- 23122028
TI  - Different IMRT solutions vs. 3D-conformal radiotherapy in early stage Hodgkin's
      Lymphoma: dosimetric comparison and clinical considerations.
AB  - BACKGROUND: Radiotherapy in Hodgkin's Lymphoma (HL) is currently evolving with
      new attempts to further reduce radiation volumes to the involved-node concept
      (Involved Nodes Radiation Therapy, INRT) and with the use of intensity modulated
      radiotherapy (IMRT). Currently, IMRT can be planned and delivered with several
      techniques, and its role is not completely clear. We designed a planning study on
      a typical dataset drawn from clinical routine with the aim of comparing different
      IMRT solutions in terms of plan quality and treatment delivery efficiency.
      METHODS: A total of 10 young female patients affected with early stage
      mediastinal HL and treated with 30 Gy INRT after ABVD-based chemotherapy were
      selected from our database. Five different treatment techniques were compared: 3D
      CRT, VMAT (single arc), B-VMAT ("butterfly", multiple arcs), Helical Tomotherapy
      (HT) and Tomodirect (TD). Beam energy was 6 MV, and all IMRT planning solutions
      were optimized by inverse planning with specific dose-volume constraints on OAR
      (breasts, lungs, thyroid gland, coronary ostia, heart). Dose-Volume Histograms
      (DVHs) and Conformity Number (CN) were calculated and then compared, both for
      target and OAR by a statistical analysis (Wilcoxon's Test). RESULTS: PTV coverage
      was reached for all plans (V95% >= 95%); highest mean CN were obtained with HT
      (0.77) and VMAT (0.76). B-VMAT showed intermediate CN mean values (0.67), while
      the lowest CN were obtained with TD (0.30) and 3D-CRT techniques (0.30). A trend
      of inverse correlation between higher CN and larger healthy tissues volumes
      receiving low radiation doses was shown for lungs and breasts. For thyroid gland
      and heart/coronary ostia, HT, VMAT and B-VMAT techniques allowed a better sparing
      in terms of both Dmean and volumes receiving intermediate-high doses compared to
      3D-CRT and TD. CONCLUSIONS: IMRT techniques showed superior target coverage and
      OAR sparing, with, as an expected consequence, larger volumes of healthy tissues
      (lungs, breasts) receiving low doses. Among the different IMRT techniques, HT and
      VMAT showed higher levels of conformation; B-VMAT and HT emerged as the planning
      solutions able to achieve the most balanced compromise between higher
      conformation around the target and smaller volumes of OAR exposed to lower doses
      (typical of 3D-CRT).

PMID- 23122030
TI  - Delayed cochlear implant complication: skin flap elevation following excessive
      nose blowing: our experience in three patients' and case series with literature
      review.

PMID- 23122031
TI  - The use of radiofrequency in the treatment of twin reversed arterial perfusion
      sequence: a case series and review of the literature.
AB  - OBJECTIVE: To evaluate the initial experience at our centre in the treatment of
      monochorionic twin pregnancies complicated by twin reversed arterial perfusion
      sequence (TRAP), using radiofrequency ablation (RFA) with expandable needles, and
      to review the existing literature on the subject. STUDY DESIGN: Between July 2007
      and October 2010, 11 monochorionic twin pregnancies complicated by TRAP were
      referred to our centre. Seven patients underwent intrafetal ablation of the
      acardiac twin with RFA using LeVeenTM expandable needle electrodes. Data on the
      procedures and the obstetric outcome were reviewed, and subsequently we performed
      a review of the literature on the use of RFA in TRAP. RESULTS: Median gestational
      age at the intervention was 17(+3) weeks (range 14(+1)-23(+1) weeks). Technical
      success was obtained in all cases. Preterm premature rupture of membranes
      (PPROMs) occurred in 4/7 (57%) patients. Intrauterine death of the pump twin
      occurred in one patient at 21(+5) weeks, and one patient opted for termination of
      pregnancy because of PPROM at 21(+4) weeks. Five fetuses were delivered alive at
      a median gestational age of 33(+0) weeks (range 31(+0)-39(+5) weeks). All five
      infants (71%) were alive and had a normal examination at 6 months of age. The
      review identified 6 studies, for a total of 78 pregnancies (either monochorionc
      twins or triplets with a monochorionic component). Including our data, overall
      neonatal survival was 75/88 (85%). CONCLUSION: RFA appears to be a relatively
      safe and reliable technique in the treatment of TRAP sequence pregnancies.
      Further research is needed to define the best timing of the procedure.

PMID- 23122032
TI  - Third trimester abdominal circumference, estimated fetal weight and uterine
      artery doppler for the identification of newborns small and large for gestational
      age.
AB  - OBJECTIVE: To understand if ultrasound biometric evaluation at 30-32 weeks of
      gestation is a valuable screening tool for the detection of small-for-gestational
      age (SGA) and large-for-gestational-age (LGA) infants at birth in a low risk
      population. STUDY DESIGN: We enrolled 1848 pregnant women with singleton
      pregnancy undergoing routine fetal biometry. We divided the infants into four
      groups: moderate SGA, severe SGA, moderate LGA and severe LGA. We considered
      third-trimester estimated fetal weight (EFW), abdominal circumference (AC), EFW
      centile (EFWc), AC centile (ACc) and compared their prediction toward SGA and LGA
      to determine which of these parameters was the best estimator for fetal size.
      Then we took the strongest predictive value and added all history-related and
      ultrasound factors to run a stepdown multivariate logistic regression. All the
      variables were then dichotomized and sensitivity models only for statistically
      significant parameters were calculated. RESULTS: We identified the following
      predictive factors for each outcome: for severe SGA: EFWc with p<0.001, uterine
      artery pulsatility index (UtA PI) with p<0.002. For moderate SGA: EFWc with
      p<0.001, UtA PI with p<0.004, maternal preeclampsia p<0.002. For moderate and
      severe LGA: EFWc with p<0.001. CONCLUSION: We can detect in a low-risk population
      a group at risk of growth deviations. Adding Doppler velocimetry to 30-32 weeks
      EFWc improves the specificity (84%) regarding SGA newborns, maintaining a good
      sensitivity (71%), and reducing the population to be re-screened from 27 to 17%.
      An ultrasound examination at 34-36 weeks or the clinical assessment of maternal
      risk factors remain the best tools for LGA newborns.

PMID- 23122033
TI  - Neonatal and two-year outcomes after rupture of membranes before 25 weeks of
      gestation.
AB  - OBJECTIVE: To assess the impact of extreme preterm premature rupture of membranes
      (PPROM) <25 weeks of gestation on preterm child outcome. STUDY DESIGN:
      Retrospective study comparing the neonatal and 2-year outcomes of infants exposed
      to extremely PPROM <25 weeks with a non-exposed group of neonates in a tertiary
      care referral centre located in Paris, France, between 2003 and 2007. All women
      with singleton pregnancy and PPROM between 15(0/7) and 24(6/7) weeks of gestation
      were recruited. For each infant born alive, the next inborn neonate matched for
      gestational age and sex was selected as a control among neonates born alive after
      spontaneous preterm labour with intact membranes. The main outcome measures were
      neonatal outcome assessed by a combined criterion of adverse neonatal outcomes
      and the two-year neurodevelopmental outcome assessed by developmental Brunet
      Lezine tests and neurological examinations. RESULTS: In 78 cases of extremely
      PPROM, 22 live births occurred at a mean gestational age of 26(5/7) weeks. The
      percentage of neonates with adverse neonatal outcomes was significantly higher
      among PPROM than non-exposed cases (68.2 versus 27.3%). At 2 years of age,
      children from the PPROM group were more likely to have delayed acquisitions (64.3
      versus 15.8%) and behavioural disorders (57.1 versus 15.8%). Mean Brunet-Lezine
      language score was significantly lower among those infants (78.9 versus 96.8).
      CONCLUSION: PPROM <25 weeks is associated with increased neonatal mortality and
      morbidity and with increased risks of delayed acquisitions, behavioural disorders
      and lower language performance scores at 2 years in comparison with matched
      preterm neonates born after spontaneous preterm labour with intact membranes.

PMID- 23122034
TI  - Management of large adnexal tumors by isobaric laparoendoscopic single-site
      surgery with a wound retractor.
AB  - OBJECTIVE: To report our experience with isobaric transumbilical laparoendoscopic
      single-site surgery for the management of large adnexal tumors exceeding 500g of
      excised tissue weight including cystic contents. STUDY DESIGN: In each case, a
      wound retractor was used to make a working port through a 2.5-cm vertical
      umbilical incision. The surgical view was secured by the abdominal wall-lift
      method with an intra-abdominal fan retractor system. After the tumor was
      punctured by a SAND balloon catheter and the cystic contents were aspirated,
      surgical procedures were performed with conventional laparoscopic instruments
      under vision with a rigid 30 degrees , 5-mm EndoEYE laparoscope. Clinical data
      regarding patient demographics and surgical outcomes was retrospectively
      analyzed. RESULTS: Between October 2010 and April 2012, 35 patients with large
      adnexal tumors were treated. The median age of the patients was 31.5 years.
      Previous abdominal surgery was noted in nine cases. The median tumor diameter was
      17.7cm. Emergency surgery was performed in two cases of adnexal torsion and one
      case of tumor rupture. Three cases with intrauterine pregnancy were treated in
      the late first trimester. Unilateral salpingo-oophorectomy was performed in 24
      cases. Unilateral cystectomy was performed in five cases. Unilateral salpingo
      oophorectomy and contralateral cystectomy, and bilateral cystectomy were
      performed in two cases each. Unilateral salpingectomy, unilateral salpingo
      oophorectomy and contralateral salpingectomy were performed in one case each. The
      median excised tissue weight was 1100g. The median surgical duration was 72min,
      with median blood loss of 10mL Extended hospitalization was required in two cases
      due to elevated inflammatory parameters, one case with pregnancy due to
      hyperemesis gravidarum and one case with pregnancy due to subchorionic hematoma.
      Readmission due to postoperative pelvic abscess was noted in one case and was
      conservatively managed. Major surgical complications were not experienced. The
      present technique yielded a minimal postoperative scar concealed within the
      umbilicus. CONCLUSION: The transumbilical wound retraction system combined with
      an intra-abdominal fan retractor appears to contribute favorably to
      laparoendoscopic single-site surgery for the management of large adnexal tumors,
      because the device permits flexible and wide circumferential access by efficient
      wound retraction during instrumentation without the need for closed condition
      associated with pneumoperitoneum.

PMID- 23122035
TI  - Subsequent pregnancy outcome after previous foetal death.
AB  - OBJECTIVE: A history of foetal death is a risk factor for complications and
      foetal death in subsequent pregnancies as most previous risk factors remain
      present and an underlying cause of death may recur. The purpose of this study was
      to evaluate subsequent pregnancy outcome after foetal death and to compare cases
      of recurrent foetal death. STUDY DESIGN: A retrospective cohort study in a
      tertiary referral centre. All women with a stillbirth beyond 16 weeks of
      gestation between January 1999 and December 2004 (n=193) were identified. After
      providing informed consent, the medical records of 163 women were reviewed until
      August 2006 in terms of clinical, medical, obstetric and paediatric data of the
      pregnancy after the index pregnancy that resulted in foetal death. The cause of
      death for reported cases of foetal death and recurrent foetal death were
      classified by a multidisciplinary team according to the Tulip classification.
      RESULTS: Recurrent foetal death occurred in 11 cases, and various causes were
      identified. The cause of death was explained in seven cases. An association was
      found between the index foetal death and subsequent foetal death in some cases,
      especially in early gestation. CONCLUSIONS: This study illustrates the importance
      of classifying the cause of recurrent foetal death and contributing risk factors
      using the same classification system. This provides more insight into the
      pathophysiological pathways leading to foetal death, and enables meaningful
      comparisons to be made in recurrent foetal death. This is required before
      preventive strategies can be instituted and implemented to reduce the risk of
      foetal death.

PMID- 23122036
TI  - Prostate cancer imaging: what the urologist wants to know.
AB  - No consensus exists at present regarding the use of imaging for the evaluation of
      prostate cancer. Ultrasonography is mainly used for biopsy guidance and magnetic
      resonance imaging is the mainstay in evaluating the extent of local tumor.
      Computed tomography and radionuclide bone scanning are mainly reserved for
      assessment of advanced disease. Positron emission tomography is gaining
      acceptance in the evaluation of treatment response and recurrence. The
      combination of anatomic, functional, and metabolic imaging modalities has promise
      to improve treatment. This article reviews current imaging techniques and touches
      on the evolving technologies being used for detection and follow-up of prostate
      cancer.

PMID- 23122037
TI  - Imaging prostate cancer.
AB  - This article reviews the anatomy of the prostate gland, magnetic resonance (MR)
      imaging techniques, and the role MR imaging in the setting of prostate cancer.
      Sequences discussed include T2-weighted MR imaging, proton ((1)H) MR
      spectroscopic imaging, diffusion-weighted MR imaging, and dynamic contrast
      enhanced MR imaging. MR imaging can be applied as an adjuvant tool to establish
      the diagnosis, localize, determine the extent, and estimate the aggressiveness of
      prostate cancers. The role of transrectal ultrasonography, computed tomography,
      and radionuclide scans is also briefly discussed.

PMID- 23122038
TI  - Role of transrectal ultrasonography in prostate cancer.
AB  - Transrectal ultrasound and ultrasound guided prostate biopsy is the current
      standard for detecting prostate cancer. Newer techniques such as elastography and
      contrast enhanced ultrasound may help in lesion detection and monitoring.
      Advances are occurring in several areas including multiparametric MRI,
      understanding of the nature of prostate cancer and new therapies including focal
      therapy and active surveillance. These changes are creating an increasing role
      for targeted biopsies following MRI and for use of MRI for treatment monitoring.

PMID- 23122039
TI  - Imaging of recurrent prostate cancer.
AB  - Approximately 30% of patients who underwent radical prostatectomy or radiation
      therapy will develop biochemical recurrent disease. Biochemical recurrent disease
      is defined as an increase in the serum value of prostate-specific antigen (PSA)
      after reaching the nadir. Prostate recurrence can present as PSA-only relapse,
      local recurrent disease, distant metastases, or a combination of local and
      distant recurrence. In this review, the role of magnetic resonance imaging in the
      work-up of recurrent prostate cancer is discussed.

PMID- 23122040
TI  - MR imaging of urinary bladder carcinoma and beyond.
AB  - Detection of muscle invasion is a critical aspect in management of urinary
      bladder cancer. MR imaging has the potential and promise of delivering this
      premise noninvasively. This article reviews the current status of MR imaging in
      evaluation of bladder cancer. Also discussed are other important neoplastic and
      nonneoplastic conditions affecting the bladder.

PMID- 23122041
TI  - Pelvic nodal imaging.
AB  - Detection of nodal metastases in men with pelvic urogenital malignancies is
      important for accurate staging and has therapeutic and prognostic implications.
      Knowledge of clinical anatomy of these nodes and the lymphatic pathways is
      critical for assigning the correct N or M staging and to assess the treatment
      response. Both computed tomography and magnetic resonance imaging use size and
      morphologic criteria for nodal characterization. The limitations of these
      criteria have formed basis newer functional imaging tools. This article focuses
      on the clinical anatomy, pathways of lymphatic spread of malignancies, current
      criteria, and newer advances in imaging of male pelvic nodes.

PMID- 23122042
TI  - Diffusion-weighted imaging of the male pelvis.
AB  - Diffusion-weighted magnetic resonance (MR) imaging (DWI) is now widely
      incorporated as a standard MR imaging sequence for the assessment of the male
      pelvis. DWI can improve the detection, characterization, and staging of pelvic
      malignancies, such as prostate, bladder, and rectal cancers. There is growing
      interest in applying quantitative DWI for the assessment of tumor treatment
      response. In addition, the technique seems promising for the evaluation of
      metastatic nodal and bone disease in the pelvis.

PMID- 23122043
TI  - Imaging of the scrotum.
AB  - Ultrasonography is currently the imaging modality of choice when assessing
      scrotal lesions. Ultrasound findings are sometimes inconclusive, in which case
      magnetic resonance (MR) imaging might yield additional important information.
      This article reviews ultrasound and MR imaging features of various
      intratesticular and extratesticular lesions including acute and nonacute
      conditions of the scrotum. Nonneoplastic lesions that can mimic scrotal
      malignancy are discussed. Normal anatomy and imaging techniques are also
      presented.

PMID- 23122044
TI  - Penile imaging.
AB  - In Peyronie disease, magnetic resonance (MR) imaging is better than ultrasound in
      detecting impalpable plaques and plaque dimensions, whereas calcified plaques are
      better visualized on ultrasound. Ultrasound with color Doppler technique is
      superior to MR imaging in evaluating vascular causes of erectile dysfunction. In
      penile fractures, MR imaging should be performed with the patient in the erect
      position to avoid kinking between the pendulous and fixed parts and thus enable
      better demonstration of the site of tunica albuginea disruption for surgical
      planning. MR imaging is better than ultrasound in delineating primary penile
      malignancies and demonstrating lymph nodal involvement.

PMID- 23122045
TI  - Imaging in male infertility.
AB  - This article presents a radiologic perspective of male infertility. Basic
      embryologic, anatomic, and physiologic concepts underpinning male reproduction
      are explained. Common and uncommon abnormalities related to male infertility and
      subfertility are described, with emphasis on imaging findings and management
      strategies.

PMID- 23122046
TI  - Imaging of male pelvic trauma.
AB  - Prompt imaging plays an important role in the evaluation of male pelvic soft
      tissue trauma. Using appropriate imaging modalities, with optimization of
      contrast administration when appropriate, is essential for accurate diagnosis.
      Traumatic bladder rupture, either extraperitoneal or intraperitoneal, is
      diagnosed with high accuracy using computed tomography cystography. Suspicion of
      urethral injury warrants evaluation with retrograde urethrography to evaluate for
      the presence of injury and injury location. Early identification of laceration of
      the testicular tunica albuginea is essential. Understanding both normal penile
      anatomy and the imaging appearance of corpus rupture (as opposed to a hematoma)
      is imperative for proper diagnosis and management.

PMID- 23122048
TI  - Effect of ethinylestradiol dose and progestagen in combined oral contraceptives
      on plasma sex hormone-binding globulin levels in premenopausal women.

PMID- 23122049
TI  - Sequencing of the needle transcriptome from Norway spruce (Picea abies Karst L.)
      reveals lower substitution rates, but similar selective constraints in
      gymnosperms and angiosperms.
AB  - BACKGROUND: A detailed knowledge about spatial and temporal gene expression is
      important for understanding both the function of genes and their evolution. For
      the vast majority of species, transcriptomes are still largely uncharacterized
      and even in those where substantial information is available it is often in the
      form of partially sequenced transcriptomes. With the development of next
      generation sequencing, a single experiment can now simultaneously identify the
      transcribed part of a species genome and estimate levels of gene expression.
      RESULTS: mRNA from actively growing needles of Norway spruce (Picea abies) was
      sequenced using next generation sequencing technology. In total, close to 70
      million fragments with a length of 76 bp were sequenced resulting in 5 Gbp of raw
      data. A de novo assembly of these reads, together with publicly available
      expressed sequence tag (EST) data from Norway spruce, was used to create a
      reference transcriptome. Of the 38,419 PUTs (putative unique transcripts) longer
      than 150 bp in this reference assembly, 83.5% show similarity to ESTs from other
      spruce species and of the remaining PUTs, 3,704 show similarity to protein
      sequences from other plant species, leaving 4,167 PUTs with limited similarity to
      currently available plant proteins. By predicting coding frames and comparing not
      only the Norway spruce PUTs, but also PUTs from the close relatives Picea glauca
      and Picea sitchensis to both Pinus taeda and Taxus mairei, we obtained estimates
      of synonymous and non-synonymous divergence among conifer species. In addition,
      we detected close to 15,000 SNPs of high quality and estimated gene expression
      differences between samples collected under dark and light conditions.
      CONCLUSIONS: Our study yielded a large number of single nucleotide polymorphisms
      as well as estimates of gene expression on transcriptome scale. In agreement with
      a recent study we find that the synonymous substitution rate per year (0.6 * 10
      09 and 1.1 * 10-09) is an order of magnitude smaller than values reported for
      angiosperm herbs. However, if one takes generation time into account, most of
      this difference disappears. The estimates of the dN/dS ratio (non-synonymous over
      synonymous divergence) reported here are in general much lower than 1 and only a
      few genes showed a ratio larger than 1.

PMID- 23122050
TI  - Current status of Kampo medicine curricula in all Japanese medical schools.
AB  - BACKGROUND: There have been a few but not precise surveys of the current status
      of traditional Japanese Kampo education at medical schools in Japan. Our aim was
      to identify problems and suggest solutions for a standardized Kampo educational
      model for all medical schools throughout Japan. METHODS: We surveyed all 80
      medical schools in Japan regarding eight items related to teaching or studying
      Kampo medicine: (1) the number of class meetings, target school year(s), and type
      of classes; (2) presence or absence of full-time instructors; (3) curricula
      contents; (4) textbooks in use; (5) desire for standardized textbooks; (6)
      faculty development programmes; (7) course contents; and (8) problems to be
      solved to promote Kampo education. We conducted descriptive analyses without
      statistics. RESULTS: Eighty questionnaires were collected (100%). (1) There were
      0 to 25 Kampo class meetings during the 6 years of medical school. At least one
      Kampo class was conducted at 98% of the schools, >=4 at 84%, >=8 at 44%, and >=16
      at 5%. Distribution of classes was 19% and 57% for third- and fourth-year
      students, respectively. (2) Only 29% of schools employed full-time Kampo medicine
      instructors. (3) Medicine was taught on the basis of traditional Japanese Kampo
      medicine by 81% of the schools, Chinese medicine by 19%, and Western medicine by
      20%. (4) Textbooks were used by 24%. (5) Seventy-four percent considered using
      standardized textbooks. (6) Thirty-three percent provided faculty development
      programmes. (7) Regarding course contents, "characteristics" was selected by 94%,
      "basic concepts" by 84%, and evidence-based medicine by 64%. (8) Among the
      problems to be solved promptly, curriculum standardization was selected by 63%,
      preparation of simple textbooks by 51%, and fostering instructors responsible for
      Kampo education by 65%. CONCLUSIONS: Japanese medical schools only offer students
      a short time to study Kampo medicine, and the impetus to include Kampo medicine
      in their curricula varies among schools. Future Kampo education at medical
      schools requires solving several problems, including curriculum standardization.

PMID- 23122053
TI  - How to encourage use of low dead space syringes? The Viet Nam experience.

PMID- 23122052
TI  - Type I interferon response and innate immune sensing of cancer.
AB  - Unexpectedly, many cancers appear to induce a spontaneous adaptive T cell
      response. The presence of a T cell infiltrate has been linked to favorable
      clinical outcome in multiple cancer types. However, the innate immune pathways
      that bridge to an adaptive immune response under sterile conditions are poorly
      understood. Recent data have indicated that tumors can induce type I interferon
      (IFN) production by host antigen-presenting cells (APCs), which is required for a
      spontaneous T cell response in vivo. The innate immune sensing pathways that
      trigger type I IFN production are being elucidated. Host type I IFNs are also
      required for optimal therapeutic efficacy with radiation. This recently uncovered
      role for host type I IFNs for antitumor immunity has important fundamental and
      clinical implications.

PMID- 23122051
TI  - The role of microglia in brain maintenance: implications for Rett syndrome.
AB  - The role of microglia in central nervous system (CNS) pathology has been studied
      extensively, and more recently, examination of microglia in the healthy brain has
      yielded important insights into their many functions. It was long assumed that
      microglia were essentially quiescent cells, unless provoked into activation,
      which was considered a hallmark of disease. More recently, however, it has become
      increasingly clear that they are extraordinarily dynamic cells, constantly
      sampling their environment and adjusting to exquisitely delicate stimuli. Along
      these lines, our laboratory has identified a new and unexpected role for
      microglial phagocytosis - or lack thereof - in the pathophysiology of Rett
      syndrome, a neurodevelopmental disease caused by mutation of the gene encoding
      methyl-CpG binding protein (MECP)2. We have shown that specific expression of
      wild type Mecp2 in myeloid cells of Mecp2-null mice is sufficient to arrest major
      symptoms associated with this devastating disease. This beneficial effect,
      however, is abolished if phagocytic activity of microglia is inhibited. Here, we
      discuss microglial origins, the role of microglia in brain development and
      maintenance, and the phenomenon of microglial augmentation by myeloid progenitor
      cells in the adult brain. Finally, we address in some detail the beneficial roles
      of microglia as clinical targets in Rett syndrome and other neurological
      disorders.

PMID- 23122054
TI  - The infancy of robotic laparoendoscopic single-site renal surgery: waiting for
      needed technological improvements.

PMID- 23122055
TI  - Distributional fold change test - a statistical approach for detecting
      differential expression in microarray experiments.
AB  - BACKGROUND: Because of the large volume of data and the intrinsic variation of
      data intensity observed in microarray experiments, different statistical methods
      have been used to systematically extract biological information and to quantify
      the associated uncertainty. The simplest method to identify differentially
      expressed genes is to evaluate the ratio of average intensities in two different
      conditions and consider all genes that differ by more than an arbitrary cut-off
      value to be differentially expressed. This filtering approach is not a
      statistical test and there is no associated value that can indicate the level of
      confidence in the designation of genes as differentially expressed or not
      differentially expressed. At the same time the fold change by itself provide
      valuable information and it is important to find unambiguous ways of using this
      information in expression data treatment. RESULTS: A new method of finding
      differentially expressed genes, called distributional fold change (DFC) test is
      introduced. The method is based on an analysis of the intensity distribution of
      all microarray probe sets mapped to a three dimensional feature space composed of
      average expression level, average difference of gene expression and total
      variance. The proposed method allows one to rank each feature based on the signal
      to-noise ratio and to ascertain for each feature the confidence level and power
      for being differentially expressed. The performance of the new method was
      evaluated using the total and partial area under receiver operating curves and
      tested on 11 data sets from Gene Omnibus Database with independently verified
      differentially expressed genes and compared with the t-test and shrinkage t-test.
      Overall the DFC test performed the best - on average it had higher sensitivity
      and partial AUC and its elevation was most prominent in the low range of
      differentially expressed features, typical for formalin-fixed paraffin-embedded
      sample sets. CONCLUSIONS: The distributional fold change test is an effective
      method for finding and ranking differentially expressed probesets on microarrays.
      The application of this test is advantageous to data sets using formalin-fixed
      paraffin-embedded samples or other systems where degradation effects diminish the
      applicability of correlation adjusted methods to the whole feature set.

PMID- 23122056
TI  - Acoustic rhinometry, rhinomanometry and visual analogue scale before and after
      septal surgery: a prospective 10-year follow-up.
AB  - OBJECTIVES: The aim of the study was to compare rhinomanometry, acoustic
      rhinometry and subjective estimation of the nasal obstruction before and after
      septoplasty and to evaluate the long-term results of septal surgery. DESIGN:
      Prospective long-term follow-up, before and after septoplasty. SETTING:
      University tertiary-care hospital, referral centre. PARTICIPANTS: The study
      included 30 adult patients who were operated on because of septal deviation. MAIN
      OUTCOME MEASURES: Pre-operatively, acoustic rhinometry and active anterior
      rhinomanometry were performed on each subject after decongestion of the nose. A
      visual analogue scale for unilateral nasal obstruction was filled in by the
      patients. The measurements were repeated both 6 months and 10 years post
      operatively. RESULTS: A significant change in acoustic values was found during
      the long-term follow-up of 10 years. The mean minimal cross-sectional area on the
      more obstructive side was 0.35 cm(2) pre-operatively. Six months after operation,
      it was 0.52 cm(2), and 10 years after operation, it was 0.68 cm(2). The mean
      resistance fell from pre-operative 1.16 Pa/mL/s to 0.41 Pa/mL/s during the first
      6 months, but rose again to 1.21 Pa/mL/s after 10 years. Despite a tendency of
      improvement, no statistically significant change was found between pre-operative
      and postoperative values in VAS. Six months after operation 69% of the patients
      were satisfied with the result, and after ten years the amount of satisfied
      patients was 83%. CONCLUSIONS: We found an increase in acoustic values, but an
      increase in nasal resistance in the long-term follow-up. Other factors than nasal
      area may have an impact on nasal resistance and the feeling of nasal obstruction.
      The small size on the sample interfered with the results.

PMID- 23122058
TI  - Culture(s).

PMID- 23122057
TI  - Quantifying heterogeneity in emphysema from high-resolution computed tomography:
      a lung tissue research consortium study.
AB  - RATIONALE AND OBJECTIVES: To quantify spatial distribution of emphysema using
      high-resolution computed tomography (HRCT), we applied semiautomated analysis
      with internal attenuation calibration to measure regional air volume, tissue
      volume, and fractional tissue volume (FTV = tissue/[air + tissue] volume) in well
      characterized patients studied by the Lung Tissue Research Consortium (LTRC).
      METHODS: HRCT was obtained at supine end-inspiration and end-expiration, and
      prone end-inspiration from 31 patients with mild, moderate, severe, or very
      severe emphysema (stages II-V, forced expiratory volume at 1 second >75%, 51%
      75%, 21%-50% and <=20% predicted, respectively). Control data were from 20
      healthy non-smokers (stage I). Each lobe was analyzed separately. Heterogeneity
      of FTV was assessed from coefficients of variation (CV) within and among lobes,
      and the kurtosis and skewness of FTV histograms. RESULTS: In emphysema, lobar air
      volume increased up to 177% above normal except in the right middle lobe. Lobar
      tissue volume increased up to 107% in mild-moderate stages then normalized in
      advanced stages. Normally, FTV was up to 82% higher in lower than upper lobes. In
      mild-moderate emphysema, lobar FTV increased by up to 74% above normal at supine
      inspiration. In severe emphysema, FTV declined below normal in all lobes and
      positions in correlation with pulmonary function (P < .05). Markers of FTV
      heterogeneity increased steadily with disease stage in correlation with pulmonary
      function (P < .05); the pattern is distinct from that seen in interstitial lung
      disease (ILD). CONCLUSION: CT-derived biomarkers differentiate the spatial
      patterns of emphysema distribution and heterogeneity from that in ILD. Early
      emphysema is associated with elevated tissue volume and FTV, consistent with
      hyperemia, inflammation or atelectasis.

PMID- 23122059
TI  - Detection of genetic association and functional polymorphisms of UGDH affecting
      milk production trait in Chinese Holstein cattle.
AB  - BACKGROUND: We previously localized a quantitative trait locus (QTL) on bovine
      chromosome 6 affecting milk production traits to a 1.5-Mb region between BMS483
      and MNB-209 via genome scanning followed by fine mapping. RESULTS: Totally 15
      genes were mapped within such linkage region through bioinformatic analysis of
      the cattle-human comparative map and bovine genome assembly. Of them, the UDP
      glucose dehydrogenase (UGDH) was suggested as a potential positional candidate
      gene for milk production traits based on its corresponding physiological and
      biochemical functions and genetic effects. By sequencing all the coding exons and
      the untranslated regions in UGDH with pooled DNA of 8 sires represented the
      separated families detected in our previous studies, a total of ten SNPs were
      identified and genotyped in 1417 Holstein cows of 8 separation families.
      Individual SNP-based association analysis revealed 4 significant associations of
      SNP Ex1-1, SNP Int3-1, SNP Int5-1, and SNP Ex12-3 with milk yield (P < 0.05), and
      2 significant associations of SNP Ex1-1 and SNP Ex12-3 with protein yield (P <
      0.05). Furthermore, our haplotype-based association analyses indicated that
      haplotypes G-C-C, formed by SNP Ex12-2-SNP Int11-1-SNP Ex11-1, T-G, formed by SNP
      Int9-3-SNP Int9-2, and C-C, formed by SNP Int5-1-SNP Int3-1, are significantly
      associated with protein percentage (F=4.15; P=0.0418) and fat percentage
      (F=5.18~7.25; P=0.0072~0.0231). Finally, by using an in vitro expression assay,
      we demonstrated that the A allele of SNP Ex1-1 and T allele of SNP Ex11-1of UGDH
      significantly decreases the expression of UGDH by 68.0% at the RNA, and 50.1% at
      the protein level, suggesting that SNP Ex1-1 and Ex11-1 represent two functional
      polymorphisms affecting expression of UGDH and may partly contributed to the
      observed association of the gene with milk production traits in our samples.
      CONCLUSIONS: Taken together, our findings strongly indicate that UGDH gene could
      be involved in genetic variation underlying the QTL for milk production traits.

PMID- 23122060
TI  - A novel mechanism for the promotion of quercetin glycoside absorption by megalo
      alpha-1,6-glucosaccharide in the rat small intestine.
AB  - The presence of an alpha-1,6-glucosaccharide enhances absorption of water-soluble
      quercetin glycosides, a mixture of quercetin-3-O-beta-d-glucoside (Q3G, 31.8%),
      mono (23.3%), di (20.3%) and more d-glucose adducts with alpha-1,4-linkage to a d
      glucose moiety of Q3G, in a ligated small intestinal loop of anesthetized rats.
      We prepared alpha-1,6-glucosaccharides with different degrees of polymerization
      (DP) enzymatically and separated them into a megalo-isomaltosaccharide-containing
      fraction (M-IM, average DP=11.0) and an oligo-isomaltosaccharide-containing
      fraction (O-IM, average DP=3.6). Luminal injection of either saccharide fraction
      promoted the absorption of total quercetin-derivatives from the small intestinal
      segment and this effect was greater for M-IM than O-IM addition. M-IM also
      increased Q3G, but not the quercetin aglycone, concentration in the water-phase
      of the luminal contents more strongly than O-IM. The enhancement of Q3G
      solubilization in the luminal contents may be responsible for the increases in
      the quercetin glucoside absorption promoted by alpha-1,6-glucosaccharides,
      especially that by M-IM. These results suggest that the ingestion of alpha-1,6
      glucosaccharides promotes Q3G bioavailability.

PMID- 23122061
TI  - alpha-Glucosidase inhibitor from Buthus martensi Karsch.
AB  - A bioassay-guided fractionation of an ethanol extract of Buthus martensi Karsch
      led to the isolation of a potent alpha-glucosidase inhibitor (compound S). The
      structure was elucidated as a novel beta-carboline glucoalkaloid, harmanyl beta-d
      glucopyranoside, on the basis of spectral data, including (1)H NMR, (13)C NMR,
      (1)H-(1)H COSY, NOESY, and HMBC. Compound S showed potent inhibitory activity
      against alpha-glucosidase, with an IC(50) value of 24 MUM. A Lineweaver-Burk plot
      indicated that its inhibition of alpha-glucosidase was uncompetitive, with a Ki
      value of 16.1 MUM.

PMID- 23122062
TI  - Mapping of Saccharomyces cerevisiae metabolites in fermenting wheat straight
      dough reveals succinic acid as pH-determining factor.
AB  - Fermenting yeast does not merely cause dough leavening, but also contributes to
      the bread aroma and might alter dough rheology. Here, the yeast carbon metabolism
      was mapped during bread straight-dough fermentation. The concentration of most
      metabolites changed quasi linearly as a function of fermentation time. Ethanol
      and carbon dioxide concentrations reached up to 60 mmol/100g flour.
      Interestingly, high levels of glycerol (up to 10 mmol/100g flour) and succinic
      acid (up to 1.6 mmol/100g flour) were produced during dough fermentation. Further
      tests showed that, contrary to current belief, the pH decrease in fermenting
      dough is primarily caused by the production of succinic acid by the yeast instead
      of carbon dioxide dissolution or bacterial organic acids. Together, our results
      provide a comprehensive overview of metabolite production during dough
      fermentation and yield insight into the importance of some of these metabolites
      for dough properties.

PMID- 23122063
TI  - Preparative separation and purification of sulforaphene from radish seeds by high
      speed countercurrent chromatography.
AB  - Sulforaphene, a kind of isothiocyanates, derived from glucoraphenin which is the
      important ingredient of radish (Raphanus sativus L.) seeds, has shown significant
      pharmacological activities. In this paper, the separation and purification of
      sulforaphene from radish seeds, was achieved by high-speed countercurrent
      chromatography (HSCCC). A two-phase solvent system consisted of n-hexane-ethyl
      acetate-methanol-water (35:100:35:100, v/v/v/v) was applied. The revolution speed
      of the separation column, flow rate of the mobile phase and separation
      temperature were 800 rpm, 2 ml/min and 30 degrees C, respectively. From about
      1000 mg amount of the crude plant extract, 249.4 mg of pure sulforaphene was
      obtained by one-step separation on a 280 ml HSCCC column. The purified
      sulforaphene was at a high purity of 96.9% and the mass recovery was more than
      95%. The purity of sulforaphene was determined by HPLC analysis and its chemical
      structure was assessed by MS, (1)H NMR, (13)C NMR and DEPT-135 NMR.

PMID- 23122064
TI  - Thermal stability of yeast hydrolysate as a novel anti-obesity material.
AB  - We examined the thermal stability of yeast hydrolysates before and after
      ultrafiltration (UF) in vitro, and the anti-obesity activity of yeast
      hydrolysates before and after heat treatment in vivo. Yeast hydrolysate after UF
      showed significantly higher thermal stability than before UF. Yeast hydrolysates
      before and after UF showed 3 and 4 thermal transition peaks in their thermograms,
      respectively, and the total thermal denaturation enthalpies of yeast hydrolysates
      before and after UF were 69.5 and 36.5 J/g, respectively. For the anti-obesity
      activity study, yeast hydrolysates before and after heating were administered ad
      libitum with water to 7-week-old male SD rats. The administration of yeast
      hydrolysate (YH-control; no heat treatment, YH-1; heat treatment at 140 degrees
      C, and YH-2; heat treatment at 160 degrees C) significantly increased mRNA
      expression of cocaine- and amphetamine-regulated transcript (CART) compared with
      control rats (saline administration). However, there was no significant
      difference between the heat-treated groups and YH-control and there was no
      significant difference in neuropeptide Y expression between the heat-treated
      groups and YH-control. These results suggest that yeast hydrolysate can be use an
      anti-obesity material after heat treatment.

PMID- 23122065
TI  - Inhibitory effect of aqueous spinach extract on degranulation of RBL-2H3 cells.
AB  - The inhibitory effect of an aqueous extract from spinach on degranulation of RBL
      2H3 cells is herein reported. The extract significantly suppressed antigen
      induced degranulation in a dose-dependent manner without affecting cell
      viability. Active substances in the extract were heat-stable and trypsin
      resistant with molecular weights ranging from 500 Da to 14 kDa. The extract
      inhibited elevation of the intracellular Ca(2+) concentration caused by
      stimulation by antigen, while not suppressing degranulation induced by a calcium
      ionophore A23187. Immunoblot analysis revealed that the inhibitory effect results
      from downregulation of phosphorylation of both Syk kinase and
      phosphatidylinositol 3-kinase in the signalling pathways involved in
      degranulation caused by the antigen-antibody interaction. Taken together, these
      findings suggest that aqueous spinach extract has an anti-allergic activity that
      controls degranulation.

PMID- 23122066
TI  - Lipid components prepared from a freshwater Clam (Corbicula fluminea) extract
      ameliorate hypercholesterolaemia in rats fed high-cholesterol diet.
AB  - To explore the hypocholesterolaemic components in the fat fraction of freshwater
      clam extract (FCE), we further fractionated the fat fraction by silica gel column
      chromatography into nine fat subfractions. In the present study, we used
      exogenous hypercholesterolaemic rats induced by feeding a high-cholesterol diet;
      the doses of the added fat subfractions were equivalent to those in 30% FCE. Two
      (FF1, FF2) out of the nine fat subfractions strongly reduced serum cholesterol
      levels in the rats fed a high-cholesterol diet. Both FF1 and FF2 up-regulated the
      hepatic gene expression of cholesterol 7alpha-hydroxylase, a rate-limiting enzyme
      of bile acid biosynthesis. Thin-layer chromatography showed that FF1 primarily
      contained sphingolipids, while FF2 mainly contained triacylglycerols and sterol
      esters. These results indicate that fractions containing sphingolipids,
      triacylglycerols, and sterol esters are possibly responsible for the
      hypocholesterolaemic action in a novel manner through the up-regulation of the
      hepatic biosynthesis of bile acids.

PMID- 23122067
TI  - Anthraquinone profile, antioxidant and antimicrobial activity of bark extracts of
      Rhamnus alaternus, R. fallax, R. intermedia and R. pumila.
AB  - The quantity of phenols, as well as antioxidant and antimicrobial activities,
      were investigated in bark of Rhamnus alaternus L., R. fallax Boiss., R.
      intermedia Steud. et Hochst., and R. pumila Turra from natural stands in Croatia.
      The most abundant anthraquinones in the investigated extracts were chrysophanol
      in R. alaternus (3.14 mg/g), emodin in R. pumila (0.339 mg/g), and physcion in R.
      fallax (2.70 mg/g) and R. intermedia (0.285 mg/g). The species exhibiting the
      highest antioxidant activity were R. fallax and R. pumila. A positive correlation
      was observed between total phenolic and flavonoid levels of the extracts and
      antioxidant activity in some of the assays. All species showed antimicrobial
      activity against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli,
      Candida albicans, Aspergillus niger and Microsporum gypseum with minimal
      inhibitory concentrations equal to or below 2.500 mg/mL. The results indicate
      that the investigated Rhamnus species are a source of anthraquinones and other
      phenols, which act as multifunctional antioxidants with antimicrobial activity.

PMID- 23122068
TI  - Separation and purification of sulforaphene from radish seeds using macroporous
      resin and preparative high-performance liquid chromatography.
AB  - This present study described a rapid and cost-effective method for the separation
      and purification of natural sulforaphene from radish seeds by SP-700 macroporous
      resin and preparative high-performance liquid chromatography (HPLC). Sulforaphene
      with high purity and recovery was obtained by preparative HPLC with a C18 column
      and 30% methanol in ultra-pure water as the mobile phase. 12.5 kg of radish
      seeds, which contained 87.5 g of sulforaphene, produced 117.5 g of sulforaphene
      rich extract of 65.8% sulforaphene after primary separation by SP-700 macroporous
      resin. 5.9 g of 96.5% sulforaphene was obtained from 9.5 g of the sulforaphene
      rich extract after purification by preparative HPLC. The purified compound was
      assessed by analytical HPLC and characterised by ESI/MS, (1)H NMR and (13)C NMR.
      Standard curve was developed using the purified sulforaphene to allow
      quantification of sulforaphene in the extracts of radish seeds by analytical
      HPLC.

PMID- 23122069
TI  - Evaluation and characterisation of Citrullus colocynthis (L.) Schrad seed oil:
      Comparison with Helianthus annuus (sunflower) seed oil.
AB  - The physicochemical properties, fatty acid, tocopherol, thermal properties, (1)H
      NMR, FTIR and profiles of non-conventional oil extracted from Citrullus
      colocynthis (L.) Schrad seeds were evaluated and compared with conventional
      sunflower seed oil. In addition, the antioxidant properties of C. colocynthis
      seed oil were also evaluated. The oil content of the C. colocynthis seeds was
      23.16%. The main fatty acids in the oil were linoleic acid (66.73%) followed by
      oleic acid (14.78%), palmitic acid (9.74%), and stearic acid (7.37%). The
      tocopherol content was 121.85 mg/100g with gamma-tocopherol as the major one
      (95.49%). The thermogravimetric analysis showed that the oil was thermally stable
      up to 286.57 degrees C, and then began to decompose in four stages namely at
      377.4 degrees C, 408.4 degrees C, 434.9 degrees C and 559.2 degrees C. The
      present study showed that this non-conventional C. colocynthis seed oil can be
      used for food and non-food applications to supplement or replace some of the
      conventional oils.

PMID- 23122070
TI  - Syzygium aqueum leaf extract and its bioactive compounds enhances pre-adipocyte
      differentiation and 2-NBDG uptake in 3T3-L1 cells.
AB  - The insulin-like and/or insulin-sensitising effects of Syzygium aqueum leaf
      extract and its six bioactive compounds; 4-hydroxybenzaldehyde, myricetin-3-O
      rhamnoside, europetin-3-O-rhamnoside, phloretin, myrigalone-G and myrigalone-B
      were investigated in 3T3-L1 adipocytes. We observed that, S. aqueum leaf extract
      (0.04-5 MUg/ml) and its six bioactive compounds (0.08-10 MUM) at non-cytotoxic
      concentrations were effectively enhance adipogenesis, stimulate glucose uptake
      and increase adiponectin secretion in 3T3-L1 adipocytes. Clearly, the compounds
      myricetin-3-O-rhamnoside and europetin-3-O-rhamnoside showed insulin-like and
      insulin-sensitising effects on adipocytes from a concentration of 0.08 MUM. These
      compounds were far better than rosiglitazone and the other isolated compounds in
      enhancing adipogenesis, stimulating 2-NBDG uptake and increasing adiponectin
      secretion at all the concentrations tested. These suggest the antidiabetic
      potential of S. aqueum leaf extract and its six bioactive compounds. However,
      further molecular interaction studies to explain the mechanisms of action are
      highly warranted.

PMID- 23122071
TI  - Separation and quantification of water buffalo milk protein fractions and genetic
      variants by RP-HPLC.
AB  - A RP-HPLC method, developed for the separation and quantification of the most
      common genetic variants of bovine milk proteins, was successfully applied to the
      analysis of water buffalo milk. All the most common buffalo casein and whey
      proteins fractions, as well as their genetic variants, were detected and
      separated simultaneously in 40 min. Purified buffalo proteins were used as
      calibration standards and a total of 536 individual milk samples were analysed
      for protein composition. alpha(S1)-, alpha(S2)-, betagamma-, and kappa-casein
      were 32.2%, 15.8%, 36.5%, and 15.5%, respectively, of total casein content,
      whereas content of beta-Lactoglobulin was approximately 1.3 times as high as that
      of alpha-Lactalbumin. The existence of a polymorphism of kappa-casein was
      demonstrated in Mediterranean water buffalo and alpha(S1)- and kappa-casein
      genetic variants were successfully detected by RP-HPLC.

PMID- 23122072
TI  - An improved mass spectrometric method for identification and quantification of
      phenolic compounds in apple fruits.
AB  - Thirty-nine phenolic compounds were analysed using ultra high performance liquid
      chromatography (UHPLC) coupled with diode array and accurate mass spectrometry
      detection using electrospray ionisation (DAD/ESI-am-MS). Instrumental parameters
      such as scan speed, resolution, and mass accuracy were optimised to establish
      accurate mass measurements. The method was fully validated in terms of model
      deviation (r(2)>0.9990), range (typically 10-3500 ngg(-1)), intra/inter-day
      precision (<6% and <8%, respectively) and accuracy (typically 100 +/- 10%). The
      mass accuracy of each selected phenolic compound was below 1.5 ppm. The results
      confirmed that the UHPLC-DAD/ESI-am-MS method developed here was convenient and
      reliable for the determination of phenolic compounds in apple extracts.

PMID- 23122073
TI  - Thermodynamic analysis of the thermal stability of sulphonamides in milk using
      liquid chromatography tandem mass spectrometry detection.
AB  - The present study investigates the kinetics of the degradation of eight
      sulphonamides in skimmed milk when heated at 60, 70, 80, 90 and 100 degrees C
      using an LC-MS/MS methodology. To determine the thermal stability of these
      compounds, the first-order kinetic model was applied and the activation energies,
      half-lives and degradation percentages were calculated. Application of kinetic
      equations to the different heat treatments used in dairy processing indicates
      that sulphonamides are very stable during pasteurisation (63 degrees C; 30 min
      and 72 degrees C; 15s) as well as UHT sterilisation (140 degrees C; 4s). In
      contrast, the calculations performed with the kinetic model estimated losses in
      concentrations between 6.5% (sulfadimethoxine) and 85.1% (sulfamethazine) for the
      sterilisation at 120 degrees C for 20 min. The existence of thermodynamic
      compensation was also tested for sulphonamide degradation. Results show that
      enthalpy and entropy values displayed a good linear relationship, and
      thermodynamically we can establish that the thermal degradation of sulphonamides
      in skimmed milk exhibits enthalpy-entropy compensation.

PMID- 23122074
TI  - Iodine content in bread, milk and the retention of inherent iodine in commonly
      used Indian recipes.
AB  - Iodine deficiency disorders (IDD) is still a major public health problem and
      iodized salt remains the most effective means to control IDD in India. Few
      reports indicate that vegans have inadequate iodine intake while at the same time
      concerns are being raised on the implementation of universal salt iodization in
      the country. Therefore, we investigated the iodine content in bread, milk and
      commonly used Indian recipes prepared without iodized salt and the retention of
      inherent iodine therein. Results showed considerable iodine content in bread (25
      MUg/100g) and milk (303 MUg/L) as a positive fallout of universal salt
      iodization. Iodine content in 38 vegetarian recipes prepared without iodized salt
      was very low (2.9 +/- 2.4 MUg/100g). Retention of inherent iodine (65.6 +/-
      15.4%) and iodine from iodized salt (76.7 +/- 10.3%) in the same recipes was
      comparable. Thus, universal salt iodization programme remains the single most
      important source of dietary iodine for the Indian population.

PMID- 23122075
TI  - Lead and cadmium concentrations in goat, cow, sheep, and buffalo milks from
      different regions of Iran.
AB  - In total, 137 goat, cow, sheep, and buffalo milk samples were collected in
      different regions of Iran and analysed to determine concentrations of lead and
      cadmium by a graphite furnace atomic absorption spectrometric method. The mean
      recovery of the analytical method was 96.3% and 104% for cadmium and lead,
      respectively. The mean lead and cadmium contents obtained from 137 samples were
      1.93 +/- 1.48 (range: 0.18-6.11 ng/ml) and 9.51 +/- 4.93 ng/ml (range: 1.84 ng/ml
      30.50 ng/ml), respectively. Lead concentration in 8.1% of sheep and 1.9% of cow
      milk samples was higher than the newly established Codex standard. The mean
      concentrations of cadmium and lead in animals aged <= 3 years (n=80; 1.40 +/-
      1.05 ng/ml and 7.91 +/- 3.60 ng/ml, respectively) were lower than in animals aged
      >3 years (n=58; 2.69 +/- 1.67 ng/ml and 11.8 +/- 5.71 ng/ml, respectively).

PMID- 23122076
TI  - Identification of active compounds in vegetal extracts based on correlation
      between activity and HPLC-MS data.
AB  - We propose a method identifying candidates for active compounds in vegetal
      extracts. From a collection of samples, the method requires, for each sample, a
      HPLC-MS analysis and a measurement of the activity. By applying a correlation
      analysis between the activity and the chromatographic area for each interval of
      elution time and m/z ratio, the peaks corresponding to candidates for active
      compounds can be identified. Additionally, when peaks are identified, a model can
      be estimated to predict the activity in new samples. Both methods are evaluated
      in one experiment involving the phenolic extract (PE) from 22 samples of extra
      virgin olive oil (EVOO) where the activity is a cytotoxicity index against JIMT-1
      breast cancer cells. In this experiment, the samples were separated into two
      disjunct partitions: one was used for training (identification of candidates and
      estimation of prediction model), while the other was used for validation (by
      comparing the predicted and the measured activities). Three compounds were
      identified as candidates to be responsible for the cytotoxicity of the EVOO-PE
      against JIMT-1 cells. The prediction model provided an accurate estimation of the
      activity.

PMID- 23122077
TI  - Bacillus cereus AR156 induces resistance against Rhizopus rot through priming of
      defense responses in peach fruit.
AB  - The biocontrol effects of Bacillus cereus AR156 on Rhizopus rot caused by
      Rhizopus stolonifer in postharvest peach fruit and the possible mechanisms were
      investigated. The results showed that fruit treated with B. cereus AR156 had
      significantly lower disease incidence and smaller lesion diameter than the
      control fruit did. B. cereus AR156 treatment remarkably enhanced activities of
      chitinase and beta-1,3-glucanase, promoted accumulation of H(2)O(2), and improved
      total phenolic content and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical
      scavenging activity. Transcripts of four defense related genes were only
      significantly enhanced in fruit both treated with B. cereus AR156 and inoculated
      with R. stolonifer compared with those that were only treated with B. cereus
      AR156 or inoculated with R. stolonifer. These results suggest that B. cereus
      AR156 can effectively inhibit Rhizopus rot caused by R. stolonifer and enhance
      antioxidant activity in peach fruit through the priming of defense responses.

PMID- 23122078
TI  - Purification and characterization of membrane-bound polyphenoloxidase (mPPO) from
      Snake fruit [Salacca zalacca (Gaertn.) Voss].
AB  - Membrane-bound polyphenoloxidase (mPPO) an oxidative enzyme which is responsible
      for the undesirable browning reaction in Snake fruit (Salacca zalacca (Gaertn.)
      Voss) was investigated. The enzyme was extracted using a non-ionic detergent
      (Triton X-114), followed by temperature-induced phase partitioning technique
      which resulted in two separate layers (detergent-poor phase at the upper layer
      and detergent-rich phase at the lower layer). The upper detergent-poor phase
      extract was subsequently fractionated by 40-80% ammonium sulfate and
      chromatographed on HiTrap Phenyl Sepharose and Superdex 200 HR 10/30. The mPPO
      was purified to 14.1 folds with a recovery of 12.35%. A single prominent protein
      band appeared on native-PAGE and SDS-PAGE implying that the mPPO is a monomeric
      protein with estimated molecular weight of 38kDa. Characterization study showed
      that mPPO from Snake fruit was optimally active at pH 6.5, temperature 30 degrees
      C and active towards diphenols as substrates. The K(m) and V(max) values were
      calculated to be 5.46 mM and 0.98 U/ml/min, respectively, when catechol was used
      as substrate. Among the chemical inhibitors tested, l-cysteine showed the best
      inhibitory effect, with an IC(50) of 1.3 +/- 0.002 mM followed by ascorbic acid
      (1.5 +/- 0.06 mM), glutathione (1.5 +/- 0.07 mM), EDTA (100 +/- 0.02 mM) and
      citric acid (186 +/- 0.16 mM).

PMID- 23122079
TI  - Phillyrin attenuates high glucose-induced lipid accumulation in human HepG2
      hepatocytes through the activation of LKB1/AMP-activated protein kinase-dependent
      signalling.
AB  - Phillyrin, an active constituent found in many medicinal plants and certain
      functional foods, has anti-obesity activity in vivo. The aim of our study was to
      provide new data on the molecular mechanism(s) underlying the role of phillyrin
      in the prevention of high glucose-induced lipid accumulation in human HepG2
      hepatocytes. We found that phillyrin suppressed high glucose-induced lipid
      accumulation in HepG2 cells. Phillyrin strongly inhibited high glucose-induced
      fatty acid synthase (FAS) expression by modulating sterol regulatory element
      binding protein-1c (SREBP-1c) activation. Moreover, use of the pharmacological
      AMP-activated protein kinase (AMPK) inhibitor compound C revealed that AMPK is
      essential for suppressing SREBP-1c expression in phillyrin-treated cells.
      Finally, we found that liver kinase B1 (LKB1) phosphorylation is required for the
      phillyrin-enhanced activation of AMPK in HepG2 hepatocytes. These results
      indicate that phillyrin prevents lipid accumulation in HepG2 cells by blocking
      the expression of SREBP-1c and FAS through LKB1/AMPK activation, suggesting that
      phillyrin is a novel AMPK activator with a role in the prevention and treatment
      of obesity.

PMID- 23122080
TI  - Toona sinensis and its major bioactive compound gallic acid inhibit LPS-induced
      inflammation in nuclear factor-kappaB transgenic mice as evaluated by in vivo
      bioluminescence imaging.
AB  - In the present study, we investigated the anti-inflammatory effects of a
      nutritious vegetable Toona sinensis (leaf extracts, TS) and its major bioactive
      compound gallic acid (GA) by analysing LPS-induced NF-kappaB activation in
      transgenic mice, using bioluminescence imaging. Mice were challenged
      intraperitoneally with LPS (1mg/kg) and treated orally with TS or GA (100 or
      5mg/kg, respectively). In vivo and ex vivo imaging showed that LPS increased NF
      kappaB luminescence in the abdominal region, which was significantly inhibited by
      TS or GA. Immunohistochemical and ELISA analyses confirmed that TS and GA
      inhibited LPS-induced NF-kappaB, interleukin-1beta, and tumour necrosis factor
      alpha expression. Microarray analysis revealed that biological pathways
      associated with metabolism and the immune responses were affected by TS or GA.
      Particularly, LPS-induced thioredoxin-like 4B (TXNL4B) 2 expression in the small
      intestine, and TXNL4B, iNOS, and COX-2 expression in RAW 264.7 cells were
      significantly inhibited by TS or GA. Thus, the anti-inflammatory potential of TS
      was mediated by the downregulation of NF-kappaB pathway.

PMID- 23122081
TI  - Physicochemical parameters that influence carotenoids bioaccessibility from a
      tomato juice.
AB  - In vitro digestion models have been developed to estimate carotenoid
      bioavailability but most do not consider that their diffusion from fruit matrix
      to the lipid phase of the bolus could be a limiting step. Therefore we designed a
      model in which tomato juice is mixed with oil or oil/water emulsions, and the
      carotenoids diffusing to oil are measured by spectrometry. Temperature, pH and
      tomato juice/peanut oil ratio were evaluated for their influence on carotenoid
      diffusion. When oil/tomato ratio was between 0.11 and 1, extraction of lycopene
      was limited by the saturation of the oil phase. With a large excess of oil,
      diffusion was also limited, as only 31 +/- 1% of lycopene could be extracted from
      the juice. Diffusion did not vary significantly with pH but doubled when
      temperature rose from 10 degrees C to 37 degrees C. When the juice was mixed in
      an emulsion stabilised with bovine serum albumin or phospholipids the maximum
      extraction decreased to 14.5 +/- 0.2% and 18.5 +/- 1.5% respectively, indicating
      that in addition to the saturation of the oil phase at low oil/tomato ratio and
      in addition to intrinsic properties of the tomato juice in non-saturating
      conditions, lycopene diffusion was limited by the structure of the interface in
      emulsions.

PMID- 23122082
TI  - Mechanistic and conformational studies on the interaction of food dye amaranth
      with human serum albumin by multispectroscopic methods.
AB  - The mechanism of interaction between food dye amaranth and human serum albumin
      (HSA) in physiological buffer (pH 7.4) was investigated by fluorescence, UV-vis
      absorption, circular dichroism (CD), and Fourier transform infrared (FT-IR)
      spectroscopy. Results obtained from analysis of fluorescence spectra indicated
      that amaranth had a strong ability to quench the intrinsic fluorescence of HSA
      through a static quenching procedure. The negative value of enthalpy change and
      positive value of entropy change elucidated that the binding of amaranth to HSA
      was driven mainly by hydrophobic and hydrogen bonding interactions. The surface
      hydrophobicity of HSA increased after binding with amaranth. The binding distance
      between HSA and amaranth was estimated to be 3.03 nm and subdomain IIA (Sudlow
      site I) was the primary binding site for amaranth on HSA. The results of CD and
      FT-IR spectra showed that binding of amaranth to HSA induced conformational
      changes of HSA.

PMID- 23122083
TI  - In vitro and in vivo assessment of cytochrome P450-mediated herb-drug interaction
      of Ssang-hwa-tang.
AB  - We have evaluated the herb-drug interaction potential of Ssang-hwa-tang (SHT)
      mediated by cytochrome P450 (CYP) inhibition/induction. Further, the effects of
      fermentation on the CYP-mediated herb-drug interaction potential were determined.
      SHT showed inhibitory activity toward CYP1A2, but not 2A6, 2B6, 2C9, 2C19, 2D6,
      2E1, and 3A4 in human liver microsomes. The results of the enzyme kinetic study
      suggested that the SHT-induced CYP1A2 inhibition is mixed reversible inhibition.
      The hepatic CYP expression and activity in rats treated with SHT were examined.
      The expression/activity of CYP2E1 increased as a result of SHT extract treatment
      (P<0.005 or P<0.001, respectively), which raises the possibility that SHT may
      increase the toxicity of environmental toxicants through the elevation of CYP2E1
      mediated metabolic activation. SHT fermentation using Lactobacillus fermentum or
      Lactobacillus gasseri resulted in attenuation of the SHT-induced CYP1A2
      inhibition, but not CYP2E1 induction, suggesting that changes in the chemical
      composition of SHT through fermentation can affect the inhibition of CYP1A2
      activity.

PMID- 23122084
TI  - Effect of ultrasound treatments of tomato pulp on microstructure and lycopene in
      vitro bioaccessibility.
AB  - The influence of ultrasound treatments of tomato pulp on microstructure and
      lycopene in vitro bioaccessibility was investigated. To this purpose, samples
      were subjected to ultrasound at a frequency and amplitude of 24 kHz and 100 MUm,
      respectively, for increasing lengths of time. Results showed that ultrasound was
      responsible for loss of tomato cell integrity, as well as a decrease in the
      degree of pectin esterification. In contrast, rheological measurements showed
      that ultrasonically treated tomato pulp had greater gel-like properties than an
      untreated sample. It was inferred that ultrasound promoted the formation of a new
      network due to hydrogen bonding and hydrophobic interactions among the de
      esterified pectin molecules. Such a reinforcement of the tomato pulp structure
      resulted in a decrease in lycopene in vitro bioaccessibility of the
      ultrasonically treated tomato pulp, probably due to the fact that the presence of
      a stronger network may make lycopene less available to the digestion process.

PMID- 23122085
TI  - Discrimination against diacylglycerol ethers in lipase-catalysed ethanolysis of
      shark liver oil.
AB  - Lipase-catalysed ethanolysis of squalene-free shark liver oil was investigated.
      The mentioned shark liver oil was comprised mainly of diacylglycerol ether and
      triacylglycerols. In order to test discrimination against diacylglycerol ether,
      up to 10 different lipases were compared. The ratio of oil to ethanol and lipase
      stability were also evaluated. Surprisingly, lipase from Pseudomonas stutzeri was
      the fastest biocatalyst among all assayed, although poor discrimination against
      diacylglycerol ether was observed. The best results in terms of selectivity and
      stability were obtained with immobilised lipase from Candida antarctica (Novozym
      435). Ethanolysis reaction after 24h in the presence of Novozym 435 produced
      total disappearance of triacylglycerol and a final reaction mixture comprised
      mainly of diacylglycerol ethers (10.6%), monoacylglycerol ethers (32.9%) and
      fatty acid ethyl esters (46.0%). In addition, when an excess of ethanol was used,
      diacylglycerol ethers completely disappeared after 15 h, giving a final product
      mainly composed of monoacylglycerol ethers (36.6%) and fatty acid ethyl esters
      (46.4%).

PMID- 23122086
TI  - Sustainable production of pectin from lime peel by high hydrostatic pressure
      treatment.
AB  - The application of high hydrostatic pressure technology for enzymatic extraction
      of pectin was evaluated. Cellulase and xylanase under five different combinations
      (cellulase/xylanase: 50/0, 50/25, 50/50, 25/50, and 0/50 U/g lime peel) at
      ambient pressure, 100 and 200 MPa were used to extract pectin from dried lime
      peel. Extraction yield, galacturonic acid (GalA) content, average molecular
      weight (M(w,ave)), intrinsic viscosity [eta](w), and degree of esterification
      (DE) were compared to those parameters obtained for pectins extracted using acid
      and aqueous processes. Pressure level, type and concentration of enzyme
      significantly (p<0.05) influenced yield and DE of pectin. Enzyme and high
      pressure extraction resulted in yields which were significantly (p<0.05) higher
      than those using acid and aqueous extraction. Although pressure-induced enzymatic
      treatment improves pectin yield, it does not have any significant effect on
      M(w,ave) and [eta](w) of pectin extracts indicating the potential of high
      pressure treatment for enzymatic pectin production as a novel and sustainable
      process.

PMID- 23122087
TI  - HPLC confirmatory method development for the determination of seven quinolones in
      salmon tissue (Salmo salar L.) validated according to the European Union Decision
      2002/657/EC.
AB  - A confirmatory high pressure liquid chromatographic method for the determination
      of seven quinolone antibiotics in tissue of Atlantic salmon (Salmo salar L.) was
      developed. Ciprofloxacin (CIP), danofloxacin (DAN), enrofloxacin (ENR),
      sarafloxacin (SAR), oxolinic acid (OXO), nalidixic acid (NAL) and flumequine
      (FLU) were separated on a Perfectsil ODS-2 120 (250 mm * 4 mm, 5 MUm) column by
      gradient elution with a mobile phase consisting of 0.1% trifluoroacetic acid
      (pH=1), acetonitrile and methanol at 25 degrees C within 22 min. Analytes were
      monitored at 255 nm (for the determination of OXO, NAL and FLU) and 275 nm (for
      CIP, DAN, ENR and SAR) by means of photodiode array detector. Examined quinolones
      were isolated from salmon tissue by extraction with citrate buffer solution
      (pH=4.7) and purified by solid phase extraction using Oasis HLB (200mg/6 mL)
      cartridges. The developed method was fully validated in terms of selectivity,
      linearity, accuracy, precision, stability and sensitivity according to the
      European Union Decision 2002/657/EC. The accuracy of the method was additionally
      proved by its application to certified reference material of salmon tissue
      (BCR(r) 725).

PMID- 23122088
TI  - Multiple toxicity studies of trehalose in mice by intragastric administration.
AB  - In the present study, aberration, body weight, food consumption, haematology,
      organ coefficients, and both gross and microscopic appearance of some histiocytes
      were compared between the test and control groups. A sperm abnormality test, bone
      marrow cell micronucleus test, and a haematology study were conducted at levels
      of 1.25 g/kg, 2.5 g/kg, and 5 g/kg of trehalose. In both the sperm abnormality
      test and bone marrow cell micronucleus test, statistically significant
      differences were observed between the positive control and treatment groups
      (P<0.05), while no statistical difference was observed among the negative
      control, high dose, moderate dose and low dose groups (P>0.05). In the
      haematology study, there was no significant difference found from the controls at
      P>0.05. The results obtained in the present study could support the conclusion
      that consumption of trehalose has no adverse effects for humans.

PMID- 23122089
TI  - Introduction and nutritional evaluation of germinated soy germ.
AB  - Germinated soy germ (GSG) were developed and evaluated for their nutritional
      value. Separated soy germ was germinated at room temperature for 24h under
      running water. As germination progressed, the protein and fibre content of GSG
      increased slightly, while the lipid and carbon to nitrogen (C/N) ratio decreased;
      free amino acids including GABA increased considerably while free sugars
      decreased. Linoleic and linolenic acid were the most abundant unsaturated fatty
      acids in soy germ, and slight changes were observed in GSG. The tocopherol and
      isoflavone contents showed a rapid increase of 32.4% and 27.9%, respectively,
      during germination. The abundance of GABA, isoflavones and tocopherols
      demonstrates the high nutritional value of GSG and suggests that GSG can be
      utilised as a reasonable and effective source of healthy foods.

PMID- 23122090
TI  - Substrate specificity of glutamyl endopeptidase (GE): hydrolysis studies with a
      bovine alpha-casein preparation.
AB  - Glutamyl endopeptidase (GE) from AlcalaseTM 2.4 L was purified using hydrophobic
      interaction (HIC) and ion-exchange (IEX) chromatography. The yield of GE obtained
      was approximately 42%. Bovine alpha-casein (containing alpha(s1)- and alpha(s2)
      casein) was digested with GE at 37 and 50 degrees C for 4h. Samples were
      withdrawn at various time intervals and the peptides generated were analysed
      using mass spectrometry. GE activity was highly specific and hydrolysed the
      peptide bond predominantly on the carboxy side of Glu residues while hydrolysis
      on the carboxyl side of Asp residues was also observed. Hydrolysis did not occur
      when Pro was at the P(1)' position. In Glu-Glu-X (X=Arg, Asn, Ile and Ser) and
      Glu-Glu-Glu-Lys sequences, hydrolysis of Glu-X and Glu-Lys was preferred. The
      results are relevant to our understanding of the hydrolytic specificity of
      Alcalase, a food-grade proteolytic preparation containing GE activity which is
      used in the generation of casein hydrolysates.

PMID- 23122091
TI  - Chemical analysis and anti-inflammatory comparison of the cell culture of
      Glycyrrhiza with its field cultivated variety.
AB  - Suspended cells of Glycyrrhiza (CG) possessed a similar content of flavonoids and
      a lower content of triterpenes, when compared with its field cultivated
      equivalent (NG). Xylene-induced ear oedema and ovalbumin-induced mouse paw oedema
      were applied, to compare the effects of CG and NG on the acute inflammatory
      response. Extracts of the cell culture of Glycyrrhiza possessed a similar anti
      inflammatory effect to those of NG, through the enhancement of the SOD activity
      of plasma and liver tissues. The use of a cell culture of liquorice instead of
      field cultivation would be potentially profitable.

PMID- 23122092
TI  - Chemical and sensory effects of the freezing process on the aroma profile of
      black truffles (Tuber melanosporum).
AB  - The aim of this work was to evaluate the effect of freezing black truffles (Tuber
      melanosporum) on their aroma both in sensory and chemical terms. The truffles
      were frozen at temperatures of -20 to -80 degrees C. Descriptive and
      discriminative sensory and chemical analyses, based on headspace solid phase
      microextraction followed by gas chromatography-mass spectrometry analysis (HS
      SPME-GC-MS), were carried out after 1, 20, 40 and 60 days. Fifteen compounds with
      high aromatic potential in truffles were determined. Their selective ion peak
      areas were calculated, summed and expressed as percentage of active odour
      compound, in order to monitor changes in odour profile. The aroma of frozen
      truffles differed significantly from the aroma of fresh truffles. Volatile
      composition data revealed that T. melanosporum aromatic profile is deeply
      modified as a consequence of a freezing process. These aromatic changes could
      explain the loss of freshness observed in all frozen truffles. Methional and some
      phenols were suggested as markers of freezing time. Interestingly, 1-octen-3-one
      appeared as a general marker of freezing process.

PMID- 23122093
TI  - Antiproliferative and immunoactivatory ability of an enzymatic extract from rice
      bran.
AB  - The validation of natural products as source of functional foods or
      nutraceuticals has become an important issue in current health research. Thus,
      the present work has tested on MOLT-4 cells (human T cell acute lymphoblastic
      leukemic) the antiproliferative effect of a water-soluble enzymatic extract from
      rice bran (EERB). Present work shows that EERB induces cellular death in MOLT-4
      cells in a dose-dependent way (0-10mg/mL) but not in non-tumoral lymphocytes.
      Flow cytometric analysis of MOLT-4 cells treated with EERB showed the presence of
      death cells by apoptosis rather than necrosis. Additionally, EERB also exerts an
      immunoactivatory effect on N13 microglia cells, by inducing TNF-alpha (tumour
      necrosis factor-alpha) expression, which plays a key role in the innate immune
      response to infection. Accordingly, we can propose EERB as a useful natural
      standardized extract with antiproliferative and immunoactivatory ability that
      would be beneficial to apply in the functional food field.

PMID- 23122094
TI  - Effect of heat treatments on the essential oils of kumquat (Fortunella margarita
      Swingle).
AB  - Kumquats (Fortunella margarita Swingle) cultivated in Taiwan are eaten raw or
      made into candied fruit or fruit tea. For the experiments described in this
      paper, essential oils were obtained from kumquat peels or whole fruit by cold
      pressing, steam distillation or heating in water at 90 degrees C for 15 min
      followed by steam distillation. The volatile components contained in the
      essential oils were identified by direct injection (DI) or headspace-solid phase
      microextraction (HS-SPME) coupled with gas chromatography (GC). A total of 43
      compounds were identified, of which 37 were verified by DI/GC and 31 by HS
      SPME/GC. Hot water heating increased the yields of essential oils from both peels
      and whole fruit. The principal constituents of the oils were similar except for
      the minor compounds, including linalool, terpinen-4-ol and alpha-terpineol, the
      levels of which increased after steam distillation. The whole fruit also
      contained higher levels of terpene alcohols.

PMID- 23122095
TI  - Effect of extrusion conditions on physicochemical and sensorial properties of
      corn-broad beans (Vicia faba) spaghetti type pasta.
AB  - Corn-broad bean spaghetti type pasta was made with a corn/broad bean flour blend
      in a 70:30 ratio, through an extrusion-cooking process (Brabender 10 DN single
      screw extruder with a 3:1 compression ratio). The effect of temperature (T=80, 90
      and 100 degrees C) and moisture (M=28%, 31% and 34%) on the extrusion responses
      (specific consumption of mechanical energy and pressure) and the quality of this
      pasta-like product (expansion, cooking-related losses, water absorption, firmness
      and stickiness) was assessed. The structural changes of starch were studied by
      means of DSC and XRD. The extrusion-cooking process, at M=28% and T=100 degrees
      C, is appropriate to obtain corn-broad bean spaghetti-type pasta with high
      protein and dietary fibre content and adequate quality. The cooking
      characteristics and resistance to overcooking depended on the degree of
      gelatinisation and formation of amylose-lipid complexes. The critical
      gelatinisation point was 46.55%; beyond that point, the quality of the product
      declines.

PMID- 23122096
TI  - Quantitative determination of fatty acid chain composition in pork meat products
      by high resolution 1H NMR spectroscopy.
AB  - High resolution (1)H NMR spectroscopy was proposed for the determination of the
      fatty acid chain profile of lipids in pork meat products during ripening. Two
      typical Mediterranean PDO salami produced in Calabria, a region in the Southern
      Italy, were chosen as a case of study. Quantitative NMR analysis provided the
      fatty acid chain profiles of total lipid extracts. The transesterification of
      total lipid extracts furnished FAME mixtures that enabled quantitation of fatty
      acid acyl chains in the acylglycerol and FFA portions. In all cases, oleyl chains
      were predominant, and high amounts of polyunsaturated fatty acid chains were
      observed. The proposed spectroscopic method allowed also the estimation of the
      most important nutritional parameters of dry fermented meat products.

PMID- 23122097
TI  - GC/MS analysis of volatiles obtained by headspace solid-phase microextraction and
      simultaneous-distillation extraction from Rabdosia serra (MAXIM.) HARA leaf and
      stem.
AB  - Volatiles in Rabdosia serra were investigated by headspace solid phase
      microextraction (HS-SPME) and simultaneous-distillation extraction (SDE). The HS
      SPME technique was previously evaluated to optimise sampling conditions. A total
      of 56 and 48 compounds including alcohols, aldehydes, hydrocarbons, ketones,
      carboxylic acid, ester, and aromatics were identified in leaf and stem by
      optimised HS-SPME method (CAR/PDMS fibre; incubation time, 10 min; extraction
      temperature, 50 degrees C; extraction time, 40 min), respectively. 1-Octen-3-ol
      and (2E)-hexenal had significant contribution to R. serra aroma. Cluster analysis
      indicated that leaf and stem exhibited different volatile diversity. Air drying
      was favourable for the retention of the volatiles, while freeze- and sun-drying
      led to the loss of volatiles. SDE method preferred to the analysis of compounds
      with low volatility including fatty acids and esters. HS-SPME was a useful
      technique for the analysis of readily volatile components for the characteristics
      of R. serra aroma.

PMID- 23122098
TI  - Identification of a novel phenolic compound in litchi (Litchi chinensis Sonn.)
      pericarp and bioactivity evaluation.
AB  - Litchi (Litchi chinensis Sonn.) is a delicious fruit widely accepted by consumers
      all over the world. In this work, phytochemical investigation of litchi pericarp
      methanol extracts led to the isolation of a novel phenolic, 2-(2-hydroxyl-5
      (methoxycarbonyl) phenoxy) benzoic acid, together with kaempferol,
      isolariciresinol, stigmasterol, butylated hydroxytoluene, 3,4-dihydroxyl
      benzoate, methyl shikimate and ethyl shikimate. Most were found in litchi
      pericarp for the first time. Their structures were mainly elucidated by NMR and
      MS evidences. Antioxidant activities of the eight compounds were determined by a
      DPPH radical scavenging assay and the results showed that 2-(2-hydroxy-5
      (methoxycarbonyl) phenoxy)benzoic acid, kaempferol, isolariciresinol, butylated
      hydroxytoluene and 3,4-dihydroxy benzoate exhibited good antioxidant activities.
      An interesting finding was that butylated hydroxytoluene was detected as a
      natural antioxidant in this work, which was usually taken as a synthesized
      antioxidant. Furthermore, the novel compound exhibited no inhibitory effects
      against tyrosinase and alpha-glucosidase activities.

PMID- 23122099
TI  - Salicylic acid-induced elicitation of folates in coriander (Coriandrum sativum
      L.) improves bioaccessibility and reduces pro-oxidant status.
AB  - Foliage of Coriandrum sativum is a rich source of natural folates amenable for
      enhancement through salicylic acid-mediated elicitation, thereby holding a great
      promise for natural-mode alleviation of this vitamin (B(9)) deficiency. In the
      present study we report salicylic acid-mediated differential elicitation of
      different forms of folates - 5-methyltetrahydrofolate, 5-formyltetrahydrofolate
      and 10-formyltetrahydrofolate - their stabilities during microwave-drying and
      bioaccessibilities from fresh and dried foliage. The first two compounds nearly
      doubled and the third increased sixfold post-elicitation, with all three showing
      concomitant increase in bioaccessibilities. Although a slight decrease in
      bioaccessibility was observed in dried foliage, over twofold increase of each
      form of folate upon elicitation would deliver much higher levels of natural
      folates from this traditional culinary foliage, which is widely used in many
      cuisines. Elicitor-mediated folate enhancement also imparted reduction of
      oxidative status and the enhancement of antioxidant enzyme activities in
      coriander foliage.

PMID- 23122100
TI  - Short-term comparative study of the influence of fried edible oils intake on the
      metabolism of essential fatty acids in obese individuals.
AB  - The effect of breakfast intake of fried oils containing natural antioxidants or a
      synthetic autooxidation inhibitor on the metabolism of essential fatty acids
      focused on obese individuals. Serum levels of eicosanoids were compared in
      individuals before and after intake of different breakfasts. Univariate
      descriptive analysis was used to characterise the cohort selected for this study
      and multivariate analysis to reveal statistical differences of normalised
      eicosanoids concentrations (determined by solid-phase extraction coupled to LC
      MS/MS) depending on the edible oil used for breakfast preparation. The results
      showed that the intake of breakfast prepared with pure sunflower oil subjected to
      deep frying causes an effect over the eicosanoids profile that enables
      discrimination versus the rest of individuals. The effect was a significant
      increase in the concentration of hydroxyoctadecadienoic acid (HODE) metabolites,
      indicative markers of the intake of fried oils. The concentration of HODE
      metabolites was lower when the oil contained either natural antioxidants from
      olive-oil pomace or a synthetic autooxidation inhibitor as dimethylsiloxane. The
      comparison of the effect of fried sunflower oils with fried extra virgin olive
      oil shows the benefits associated to the consumption of the latter.

PMID- 23122101
TI  - Spatial and temporal changes in the volatile profile of Alphonso mango upon
      exogenous ethylene treatment.
AB  - Alphonso is a highly favoured and exported mango cultivar among the vast mango
      germplasm of India. Being a climacteric fruit, ethylene plays an important role
      in ripening of mango. For deeper understanding of effect of pre-climacteric
      ethylene treatment on volatile profiles of Alphonso mango, 26 volatiles were
      tracked through six ripening stages of pulp and skin of ethylene-treated and
      control Alphonso fruits. The study revealed accelerated ripening in terms of
      early appearance of ripening-specific compounds, lactones and mesifuran, upon
      ethylene treatment. While the level of lactones remained unaffected, the
      mesifuran level vastly increased upon ethylene treatment. Skin showed high
      terpene content while pulp had higher amount of lactones compared to skin. This
      work points towards involvement of ethylene as a natural hormone in the
      biosynthesis of lactones and furanones in naturally ripened fruits; whereas, an
      increase in the terpene level during ripening appears to be independent of
      ethylene.

PMID- 23122102
TI  - Comprehensive analysis of Phyteuma orbiculare L., a wild Alpine food plant.
AB  - Plants which have been traditionally eaten by the alpine population may provide
      new opportunities for agricultural development in mountain regions. In this
      context we have investigated the chemical composition of Phyteuma orbiculare
      (Campanulaceae), a perennial herb whose leaves have been eaten as salad by rural
      populations in Valais (Switzerland). Extracts of different polarities were
      subjected to comprehensive metabolite profiling using a dereplication platform
      combining HPLC-PDA-MS, and offline NMR analysis. Twenty-three compounds,
      including various phenolic glycosides, a new dimeric phenylpropanoid glucoside,
      saponins, and fatty acids were identified online, or after targeted isolation.
      Selected phenolic constituents were quantitatively assessed by HPLC-PDA analysis.
      In addition, substances relevant for nutrition, such as beta-carotene, fatty
      acids, ascorbic acid and minerals were quantified in leaves and flowers. The
      antioxidant capacity was determined with an ORAC assay, and total phenolic
      compounds were quantified. Finally, the phytochemical profile was compared to
      that of the related species P. spicatum, P. hemisphaericum and P. ovatum.

PMID- 23122103
TI  - Rapid resolution liquid chromatography-electrospray ionisation tandem mass
      spectrometry method for identification of chemical constituents in Citri
      Reticulatae Pericarpium.
AB  - Citri Reticulatae Pericarpium (CRP) is one of the most commonly used traditional
      Chinese medicines with great medicinal and dietary values. In this work, we
      developed an approach utilising rapid resolution liquid
      chromatography/electrospray ionisation tandem mass spectrometry (RRLC-ESI-MS/MS)
      for the identification and profiling of chemical composition in CRP. On the basis
      of RRLC retention times, cochromatography with available authentic standards,
      mass spectral fragmentation patterns and literature information, a total of 41
      chemical compounds, including 4 flavone-C-glycosides, 7 flavonoid-O-glycosides
      and 19 polymethoxyflavones were unambiguously identified or tentatively
      characterised in CRP. The occurrence of 1 flavone-C-glycoside and 3 cyclic
      peptides in particular has not yet been described. The results indicated that the
      developed method could serve as a rapid, effective tool for structural
      characterisation of chemical constituents in CRP.

PMID- 23122104
TI  - Novel angiotensin I-converting enzyme inhibitory peptides derived from soya milk.
AB  - Inhibitors of angiotensin I-converting enzyme (ACE) are useful in treating
      hypertension, and many have been derived from food products, including soybeans.
      Using the industrial protease PROTIN SD-NY10, we developed a processed soya milk
      (PSM) with enhanced ACE inhibitory activity. The ACE inhibitory activity of PSM
      (IC(50)=0.26 MUg/ml) was greater than that of regular soya milk (IC(50)=8.75
      MUg/ml). Eight novel ACE inhibitory peptides were purified from PSM by reversed
      phase chromatography: FFYY (IC(50),1.9 MUM), WHP (4.8 MUM), FVP (10.1 MUM),
      LHPGDAQR (10.3 MUM), IAV (27.0 MUM), VNP (32.5 MUM), LEPP (100.1 MUM), and WNPR
      (880.0 MUM). The IC(50) values of these peptides are comparable to those reported
      for other ACE inhibitory peptides derived from wheat, chicken, bonito, wine, etc.
      Due to the relatively low IC(50) values of several peptides identified in this
      study, they may serve as ideal base components of food supplements for patients
      with hypertension.

PMID- 23122105
TI  - Non-target screening of Allura Red AC photodegradation products in a beverage
      through ultra high performance liquid chromatography coupled with hybrid triple
      quadrupole/linear ion trap mass spectrometry.
AB  - The study deals with the identification of the degradation products formed by
      simulated sunlight photoirradiation in a commercial beverage that contains Allura
      Red AC dye. An UHPLC-MS/MS method, that makes use of hybrid triple
      quadrupole/linear ion trap, was developed. In the identification step the
      software tool information dependent acquisition (IDA) was used to automatically
      obtain information about the species present and to build a multiple reaction
      monitoring (MRM) method with the MS/MS fragmentation pattern of the species
      considered. The results indicate that the identified degradation products are
      formed from side-reactions and/or interactions among the dye and other
      ingredients present in the beverage (ascorbic acid, citric acid, sucrose, aromas,
      strawberry juice, and extract of chamomile flowers). The presence of aromatic
      amine or amide functionalities in the chemical structures proposed for the
      degradation products might suggest potential hazards to consumer health.

PMID- 23122106
TI  - Optimisation of inoculum concentration and incubation duration for an in vitro
      hindgut dry matter digestibility assay.
AB  - The aim was to optimise inoculum concentration and incubation duration for a
      published in vitro hindgut digestibility assay using ileal digesta (sampled from
      the chicken or rat) pertaining to a mixed human diet as the substrate. The study
      also sought to investigate the digestibility of the inoculum itself and the
      importance of correcting for this in the in vitro hindgut digestion assay. For
      two assays, hindgut dry matter digestibility (DMD) generally increased with
      inoculum concentration. A sharp increase in DMD observed at high inoculum
      concentrations may have been related to problems with filtering the inoculum. An
      inoculum concentration of 160 g/L was considered optimal based on close agreement
      of observed values with previously published in vivo hindgut dry matter
      digestibility for similar diets. One of the methods was chosen for optimisation
      of the duration of incubation. Ileal substrate organic matter digestibility (OMD)
      increased with increasing time of incubation for all diets. An incubation
      duration of 18 h using a mean inoculum digestibility value for calculation
      purposes was considered optimal based on observed in vivo hindgut DMD values in
      humans, but there was little difference in estimated in vitro hindgut DMD between
      18 and 24h incubation durations. Although considerably lower than the OM
      digestibility of the substrate (no less than 51% after 48 h), the OM
      digestibility of the inoculum (13% after 48 h) itself was of significance in
      calculating estimated digestibility. The optimised assay gave realistic hindgut
      OMD values ranging from 55% to 79% (Wheat Bran Diet and Pectin Diet,
      respectively) using an 18-h incubation duration.

PMID- 23122107
TI  - Comparative analysis of peroxidase profiles in Chinese kale (Brassica alboglabra
      L.): evaluation of leaf growth related isozymes.
AB  - Plant peroxidases (EC 1.11.1.7) with different isoforms catalyze various
      reactions in plant growth and development. However, it is difficult to elucidate
      the function of each isozyme in one plant. Here, we compared profiles of entire
      isozyme in young seedling and mature leaves of Chinese kale (Brassica alboglabra
      L.) on zymogram and ion exchange chromatography in order to investigate leaf
      growth related peroxidase isozymes. The results showed that four isozymes were
      constitutively expressed in kale leaves, whereas other two isozymes were induced
      in the mature leaves. The Mono Q ion exchange chromatography separated the six
      isozymes into two major groups due to the difference in their isoelectric points.
      The results suggested that although there were several isozymes in the leaves of
      Chinese kale, one isozyme functioned mainly through the leaf development. Two
      anionic isozymes with molecular weights lower than 32 kDa were considered mature
      related.

PMID- 23122108
TI  - Maple polyphenols, ginnalins A-C, induce S- and G2/M-cell cycle arrest in colon
      and breast cancer cells mediated by decreasing cyclins A and D1 levels.
AB  - Polyphenols are bioactive compounds found in plant foods. Ginnalins A-C are
      polyphenols present in the sap and other parts of the sugar and red maple species
      which are used to produce maple syrup. Here we evaluated the antiproliferative
      effects of ginnalins A-C on colon (HCT-116) and breast (MCF-7) tumourigenic and
      non-tumourigenic colon (CCD-18Co) cells and investigated whether these effects
      were mediated through cell cycle arrest and/or apoptosis. Ginnalins A-C were
      twofold more effective against the tumourigenic than non-tumourigenic cells.
      Among the polyphenols, ginnalin A (84%, HCT-116; 49%, MCF-7) was more effective
      than ginnalins B and C (50%, HCT-116; 30%, MCF-7) at 50 MUM concentrations.
      Ginnalin A did not induce apoptosis of the cancer cells but arrested cell cycle
      (in the S- and G(2)/M-phases) and decreased cyclins A and D1 protein levels.
      These results suggest that maple polyphenols may have potential cancer
      chemopreventive effects mediated through cell cycle arrest.

PMID- 23122109
TI  - Resveratrols in Vitis berry skins and leaves: their extraction and analysis by
      HPLC.
AB  - An orthogonal L(36) (6)(5) test design was applied to select the optimum
      conditions for extracting resveratrols from grape berry skins and leaves. Solvent
      choice was the most important factor in the extraction of resveratrols, and mixed
      methanol and ethyl acetate [50:50 (v/v)] had much higher extraction efficiency
      than the other five solvents tested. For extracting resveratrols, 1g of berry
      skins or leaf tissue extracted in 10 mL methanol and ethyl acetate [50:50 (v/v)]
      for 24h at 25 degrees C in darkness was the optimized extraction condition. The
      optimized analytical method for HPLC was a multi-step gradient elution using
      acetonitrile and water. The optimized method was used to determine resveratrols
      among three different cultivars. The cultivar 'Zhi 168' had the highest total
      resveratrols in berry skins while 'Saint-Emilion' had the lowest resveratrols.
      The resveratrol content of 'Beta' was between that of 'Zhi 168' and 'Saint
      Emilion'.

PMID- 23122110
TI  - Synthesis of quinoline derivatives of tetrahydrocurcumin and zingerone and
      evaluation of their antioxidant and antibacterial attributes.
AB  - Tetrahydrocurcumin (THC, 1) and zingerone (2) are biologically active molecules
      originating from the important spices turmeric and ginger, respectively. Novel
      quinoline derivatives of THC and zingerone have been synthesised by an efficient
      protocol involving their reaction with substituted 2-aminobenzophenones and 2
      aminoacetophenone. Radical-scavenging activities (RSA) of THC, zingerone and
      their quinoline derivatives were evaluated. The amino-substituted quinoline
      derivative of THC, 1e, showed antioxidant activity superior to those of 1 and 1a.
      Derivatives 1b, 1c, 1d and 1f exhibited relatively lower RSA at equimolar
      concentrations (~50-55 MUmol). A similar trend was also seen in zingerone (2) and
      its derivatives (2a-2e), with 2e displaying the best RSA. Derivatives of THC (1a
      1f) showed stronger antimicrobial activity than THC (1) against Staphylococcus
      aureus, Bacillus cereus, Escherichia coli, and Yersinia enterocolitica. Also,
      derivatives of zingerone (2b-2e) exhibited lower minimum inhibitory
      concentrations (MIC) values than zingerone (2) and its derivative, 2a for both
      Gram-positive and Gram-negative bacteria. The molecules may have potential
      pharmacological applications.

PMID- 23122111
TI  - Neferine induces reactive oxygen species mediated intrinsic pathway of apoptosis
      in HepG2 cells.
AB  - Evidence has accumulated concerning the medicinal application of Nelumbo nucifera
      in the treatment of various diseases. Neferine, an alkaloid from N. nucifera was
      found to exert cytotoxicity on liver cancer cells HepG2 in a dose-dependent
      manner. We evaluated its anticancer potential by studying its effect on
      mitochondrial membrane potential, intracellular calcium levels [Ca(2+)](i), cell
      membrane integrity, apoptotic body formation and DNA fragmentation in cultured
      HepG2 cells. The reactive oxygen species level has been increased upon neferine
      treatment with concomitant decrease in reduced glutathione. Our data further
      indicate reduction of DeltapsiM and increased [Ca(2+)](i) during apoptosis
      induction by neferine with increased expression of apoptotic proteins such as
      Bax, Bad, cleaved forms of caspase 3, caspase 9 and PARP, with the downregulation
      of anti-apoptotic protein Bcl2 in HepG2 cells. Moreover, the expressions of
      tumour suppressor proteins p53 and PTEN were upregulated along with the
      downregulation of P-Akt. In addition, expression levels of TNF-alpha, p38 and
      ERK1/2 MAP kinases were increased upon neferine treatment. These results imply
      that mitochondrial-mediated ROS generation induced by neferine leads to caspase
      dependent apoptosis in HepG2 cells.

PMID- 23122112
TI  - Electronic nose and GC-MS analysis of volatile compounds in Tuber magnatum Pico:
      evaluation of different storage conditions.
AB  - The characteristic aromatic composition of white truffles (Tuber magnatum Pico)
      determines its culinary and commercial value. However modifications of truffle
      organoleptic proprieties occur during preservation. A study of headspace of white
      truffles by using Electronic nose (E-nose), gas chromatography-mass spectrometry
      (GC-MS) and sensory analyses was performed. Truffles were stored at different
      conditions for 7 days: +4 and +8 degrees C wrapped in blotting paper or covered
      by rice or none of the above. Headspace E-nose measurements and sensory analyses
      were performed each day. Statistical multivariate analysis of the data showed the
      capability of E-nose to predict sensorial analysis scores and to monitor aroma
      profile changes during storage. Truffle's volatile molecules were also extracted
      by headspace solid phase microextraction technique and separated and identified
      by GC-MS. Partial Components Analysis of data was performed. E-nose and GC-MS
      results were in agreement and showed that truffle storage in paper at +8 degrees
      C seemed to be the best storage condition.

PMID- 23122113
TI  - A sensitive enzyme-linked immunosorbent assay for the determination of fish
      protein in processed foods.
AB  - Fish is one of the most common causes of food allergy and its major allergen is
      parvalbumin, a 12 kDa muscular protein. In this study, a sandwich enzyme-linked
      immunosorbent assay (ELISA) for the determination of fish protein in processed
      foods was developed using a polyclonal antibody raised against Pacific mackerel
      parvalbumin. The developed sandwich ELISA showed 22.6-99.0% reactivity (based on
      the reactivity to Pacific mackerel parvalbumin) to parvalbumins from various
      species of fish. The limits of detection and quantitation were estimated to be
      0.23 and 0.70 MUg protein per g of food, respectively. When the sandwich ELISA
      was subjected to inter-laboratory validation, spiked fish protein was recovered
      from five model processed foods in the range of 69.4-84.8% and the repeatability
      and reproducibility relative standard deviations were satisfactorily low (<=
      10.5%). Thus, the sandwich ELISA was judged to be a useful tool to determine fish
      protein in processed foods.

PMID- 23122114
TI  - Hair mercury levels and food consumption in residents from the Pearl River Delta:
      South China.
AB  - The Pearl River Delta (PRD) is located in the Southern part of China and is the
      main region for fish culture in Guangdong Province. In order to assess the
      potential health risks associated with dietary consumption of mercury, hair
      samples from 91 urban, town and fishing village residents, 37 species of fish,
      cereal, vegetables, and meat samples were collected. The average total mercury
      (THg) and methylmercury (MeHg) concentrations in hair were 1.08 +/- 0.94 and 0.58
      +/- 0.59 MUg/g, respectively. Daily Hg intake via fish consumption is
      significantly correlated with THg and MeHg accumulated in human hair (r=0.48,
      p<0.01; r=0.43, p<0.01). The estimated daily intake of Hg via different food
      types showed that both fish and cereal consumption were the two main routes of Hg
      exposure for residents in the sampling areas. Besides food intake, smoking was
      also an important source for daily THg intake in the smoke group, contributing 11
      18% to EDI of THg.

PMID- 23122115
TI  - Batch and continuous synthesis of lactulose from whey lactose by immobilized beta
      galactosidase.
AB  - In this study, lactulose synthesis from whey lactose was investigated in batch
      and continuous systems using immobilized beta-galactosidase. In the batch system,
      the optimal concentration of fructose for lactulose synthesis was 20%, and the
      effect of galactose, glucose and fructose on beta-galactosidase activity was
      determined for hydrolysis of whey lactose and the transgalactosylation reaction
      for lactulose synthesis. Galactose and fructose were competitive inhibitors, and
      glucose acted as a noncompetitive inhibitor. The inhibitory effects of galactose
      and glucose were stronger in the transgalactosylation reaction than they were in
      the hydrolysis reaction. In addition, when immobilized beta-galactosidase was
      reused for lactulose synthesis, its catalytic activity was retained to the extent
      of 52.9% after 10 reuses. Lactulose was synthesized continuously in a packed-bed
      reactor. We synthesized 19.1g/l lactulose during the continuous flow reaction at
      a flow rate of 0.5 ml/min.

PMID- 23122116
TI  - Quantitative analysis of fungicide azoxystrobin in agricultural samples with
      rapid, simple and reliable monoclonal immunoassay.
AB  - This work presents analytical performance of a kit-based direct competitive
      enzyme-linked immunosorbent assay (dc-ELISA) for azoxystrobin detection in
      agricultural products. The dc-ELISA was sufficiently sensitive for analysis of
      residue levels close to the maximum residue limits. The dc-ELISA did not show
      cross-reactivity to other strobilurin analogues. Absorbance decreased with the
      increase of methanol concentration in sample solution from 2% to 40%, while the
      standard curve became most linear when the sample solution contained 10%
      methanol. Agricultural samples were extracted with methanol, and the extracts
      were diluted with water to 10% methanol adequate. No significant matrix
      interference was observed. Satisfying recovery was found for all of spiked
      samples and the results were well agreed with the analysis with liquid
      chromatography. These results clearly indicate that the kit-based dc-ELISA is
      suitable for the rapid, simple, quantitative and reliable determination of the
      fungicide.

PMID- 23122117
TI  - Comparison of different methods to quantify fat classes in bakery products.
AB  - The definition of fat differs in different countries; thus whether fat is listed
      on food labels depends on the country. Some countries list crude fat content in
      the 'Fat' section on the food label, whereas other countries list total fat. In
      this study, three methods were used for determining fat classes and content in
      bakery products: the Folch method, the automated Soxhlet method, and the AOAC
      996.06 method. The results using these methods were compared. Fat (crude)
      extracted by the Folch and Soxhlet methods was gravimetrically determined and
      assessed by fat class using capillary gas chromatography (GC). In most samples,
      fat (total) content determined by the AOAC 996.06 method was lower than the fat
      (crude) content determined by the Folch or automated Soxhlet methods.
      Furthermore, monounsaturated fat or saturated fat content determined by the AOAC
      996.06 method was lowest. Almost no difference was observed between fat (crude)
      content determined by the Folch method and that determined by the automated
      Soxhlet method for nearly all samples. In three samples (wheat biscuits, butter
      cookies-1, and chocolate chip cookies), monounsaturated fat, saturated fat, and
      trans fat content obtained by the automated Soxhlet method was higher than that
      obtained by the Folch method. The polyunsaturated fat content obtained by the
      automated Soxhlet method was not higher than that obtained by the Folch method in
      any sample.

PMID- 23122118
TI  - CODEX-compliant eleven organophosphorus pesticides screening in multiple
      commodities using headspace-solid phase microextraction-gas chromatography-mass
      spectrometry.
AB  - A headspace-solid phase microextraction-gas chromatography-mass spectrometric (HS
      SPME-GC-MS, hereafter abbreviated as "SPME") method was developed for dedicated
      organophosphorus (OP) pesticides assessment in multiple vegetable and fruit
      commodities. Specific extraction variables were optimised to achieve harmonised
      extraction performance of eleven OPs in a great span of seven characteristic
      commodities cataloged in Codex Alimentarius Commission. Comprehensive validation
      study confirmed analytical robustness of the SPME treatment in turnip, green
      cabbage, French beans, eggplant, apple, nectarine and grapes. Based on range
      specific evaluation, extraction of individual OPs was characterised by sub-ppb
      level sensitivity and a wide 0.01-2.5 mg L(-1) dynamic range. Effective sample
      clean-up afforded precise quantification (0.5-10.9% R.S.D.) within a 70-120%
      recovery range at the MRL levels specified for individual commodities. Compared
      to conventional methods currently used, the SPME treatment developed here is
      quick, accurate, and relatively environmental friendly; it represents an
      attractive, practical way to deliver international standards in OP screening
      routines.

PMID- 23122119
TI  - Nutrients, phytochemicals and bioactivity of wild Roman chamomile: a comparison
      between the herb and its preparations.
AB  - Roman chamomile, Chamaemelum nobile L. (Asteraceae), has been used for medicinal
      applications, mainly through oral dosage forms (decoctions and infusions).
      Herein, the nutritional characterisation of C. nobile was performed, and herbal
      material and its decoction and infusion were submitted to an analysis of
      phytochemicals and bioactivity evaluation. The antioxidant activity was
      determined by free radicals scavenging activity, reducing power and inhibition of
      lipid peroxidation, the antitumour potential was tested in human tumour cell
      lines (breast, lung, colon, cervical and hepatocellular carcinomas), and the
      hepatotoxicity was evaluated using a porcine liver primary cell culture. C.
      nobile proved to be an equilibrated valuable herb rich in carbohydrates and
      proteins, and poor in fat, providing tocopherols, carotenoids and essential fatty
      acids (C18:2n6 and C18:3n3). Moreover, the herb and its infusion are a source of
      phenolic compounds (flavonoids such as flavonols and flavones, phenolic acids and
      derivatives) and organic acids (oxalic, quinic, malic, citric and fumaric acids)
      that showed antioxidant and antitumour activities, without hepatotoxicity. The
      most abundant compounds in the plant extract and infusion were 5-O-caffeoylquinic
      acid and an apigenin derivative. These, as well as other bioactive compounds, are
      affected in C. nobile decoction, leading to a lower antioxidant potential and
      absence of antitumour potential. The plant bioactivity could be explored in the
      medicine, food, and cosmetic industries.

PMID- 23122120
TI  - Gangliosides and sialic acid effects upon newborn pathogenic bacteria adhesion:
      an in vitro study.
AB  - The effect of the main gangliosides (GM(1), GM(3), GD(3)) and free sialic acid
      (Neu5Ac) upon the adhesion of pathogenic bacteria implicated in infant diarrhoea
      is assessed in vitro using the Caco-2 cell line. Concentrations of the bioactive
      compounds found in the bioaccessible (soluble) fraction of infant formula and
      human milk are employed. Bacterial adhesion behaviour included enterotoxigenic
      Escherichia coli (ETEC), enteropathogenic E.coli (EPEC), Listeria monocytogenes,
      Salmonella entericaserovartyphi, Shigella sonnei, Campylobacter jejuni and
      Helicobacter pylori. Three different approaches were assayed: pre-incubation of
      bacteria and compounds before addition to cells (competition); pre-incubation of
      the cells with compounds (exclusion); and pre-incubation of cells with bacteria
      (displacement). Furthermore, the spatial localization of the most abundant
      gangliosides, GM(3) and GD(3), in Caco-2 cells has been determined using confocal
      microscopy. Results show that GM(3), GD(3), GM(1) and Neu5Ac at the assayed
      concentrations are able to interfere with the adhesion of several pathogenic
      bacteria involved in neonatal diseases-the greatest effect corresponding to
      Neu5Ac, followed by GD(3), GM(1) and GM(3). Gangliosides GM(3) and GD(3) are
      located in the apical and basolateral membranes of the Caco-2 cells.

PMID- 23122121
TI  - A simple GC-MS method for the screening of betulinic, corosolic, maslinic,
      oleanolic and ursolic acid contents in commercial botanicals used as food
      supplement ingredients.
AB  - The occurrence of triterpene pentacyclic acids in plants is extensive, but little
      is known about their availability in commercial extracts. A simple GC-MS method
      for the simultaneous determination of betulinic, corosolic, maslinic, oleanolic
      and ursolic acids was developed and applied to 38 different commercial plant
      extracts sold as ingredients for dietary supplements. A suitable protocol was set
      up to perform routine control of a diverse array of samples with different
      botanical, chemical and physical characteristics. Remarkable quantities of
      corosolic acid were found in dried extracts from aerial parts of Lagerstroemia
      speciosa and Ortosiphon stamineus (14233 and 1132 mg/kg, respectively), while
      oleanolic acid was abundant in O. stamineus and Crataegus monogyna flowers (2774
      and 2339 mg/kg); ursolic was identified in O. stamineus, C. monogyna, L. speciosa
      and Arctostaphylos uva-ursi leaves (7773, 4165, 2108 and 1034 mg/kg). Only L.
      speciosa was rich in maslinic acid (4958 mg/kg), while minor amounts of betulinic
      acid (257 and 80 mg/kg) were detected in L. speciosa and C. monogyna extracts.
      Lower quantities of triterpenic acids were identified in dried extracts of
      Harpagophyton procumbens root, propolis, Punica granatum root, Styrax benzoin,
      Vaccinium myrtillus fruits and Vitis vinifera seeds. Decoctions and fluid
      extracts lacked or contained very low amounts of triterpenic acids. Results are
      discussed in terms of quality and safety of these ingredients.

PMID- 23122122
TI  - The importance of amylose and amylopectin fine structures for starch
      digestibility in cooked rice grains.
AB  - Statistically and causally meaningful relationships are established between
      starch molecular structures (obtained by size-exclusion chromatography, proton
      NMR and multiple-angle laser light scattering) and digestibility of cooked rice
      grains (measured by in vitro digestion). Significant correlations are observed
      between starch digestion rate and molecular structural characteristics, including
      fine structures of the distributions of branch (chain) lengths in both amylose
      and amylopectin. The in vitro digestion rate tends to increase with longer
      amylose branches and smaller ratios of long amylopectin and long amylose branches
      to short amylopectin branches, although the statistical analyses show that
      further data are needed to establish this unambiguously. These new relationships
      between fine starch structural features and digestibility of cooked rice grains
      are mechanistically reasonable, but suggestive rather than statistically
      definitive.

PMID- 23122123
TI  - 'Emerging' mycotoxins in cereals processing chains: changes of enniatins during
      beer and bread making.
AB  - Enniatins represent an emerging food safety issue because of their extensive
      incidence, documented in recent decades, in various small grain cereals. This
      study was concerned with the fate of these Fusarium mycotoxins within malting,
      brewing, milling and baking, when employed for the processing of contaminated
      barley and wheat. Besides enniatins A, A1, B and B1, also deoxynivalenol and its
      conjugated form (deoxynivalenol-3-glucoside) were determined in almost all tested
      cereal-based samples. Significant decline of enniatins occurred within all
      technologies, with the largest drop in their concentrations observed in the
      brewing process. While enniatins were not detectable in final beers, they were
      almost quantitatively transferred to spent grains, probably because of their
      limited water solubility. Regarding bread baking, levels of enniatins decreased
      down to 30% of their concentration in the initial flour used for baking. In this
      case, degradation at higher temperatures might be assumed.

PMID- 23122124
TI  - In vitro inhibition of dipeptidyl peptidase IV by peptides derived from the
      hydrolysis of amaranth (Amaranthus hypochondriacus L.) proteins.
AB  - Bioactive compounds present in foods could potentially have beneficial effects on
      human health. In this study we report the in vitro inhibitory capacity of
      peptides released from amaranth seed proteins after enzymatic digestion, against
      dipeptidyl peptidase IV (DPPIV); an enzyme known to deactivate incretins,
      hormones involved in insulin secretion. Other seeds, such as soybean, black bean,
      and wheat were also tested. The highest inhibition of DPPIV was observed with
      amaranth peptides released after simulated gastrointestinal digestion, showing an
      IC(50) of 1.1mg/mL in a dose-dependent manner. In silico tryptic digestion of
      amaranth globulins was carried out releasing peptides larger than 13 residues.
      Some of these peptides were used for the in silico prediction of their binding
      modes with DPPIV. Docking models showed that the possible mechanism of globulin
      peptides to inhibit DPPIV was through blocking the active dimer formation.
      Peptides were also found inside the major cavity where the natural substrates
      reach the catalytic site of the enzyme. This is the first report of the
      identification of inhibitory DPPIV peptides from amaranth hydrolysates and the
      prediction of their binding modes at the molecular level, leading to their
      possible use as functional food ingredients in the prevention of diabetes.

PMID- 23122125
TI  - Dietary Monascus adlay supplements facilitate suppression of cigarette smoke
      induced pulmonary endoplasmic reticulum stress, autophagy, apoptosis and
      emphysema-related PLGF in the rat.
AB  - Cigarette smoke (CS) exposure may cause oxidative stress in the lung, leading to
      cell death and long-term injury. Monascus adlay (MA) with antioxidant components
      produced by inoculating adlay (Cois lachrymal-jobi L. var. ma-yuen Stapf) with
      Monascus purpureus may protect lung against CS-induced lung injuries in rats. MA
      and lovastatin had higher antioxidant activities than either M. purpureus or
      adlay. CS exposure caused significant lung damage, as evidenced by higher levels
      of reactive oxygen species (ROS), neutrophil infiltration, dityrosine and 4-HNE,
      as well as lower levels of Mn-superoxide dismutase and catalase expression. Lung
      tissues with CS exposure had higher levels of ER stress, apoptosis, autophagy and
      emphysema-related placenta growth factor (PlGF) expressions. All CS-induced
      injuries were significantly suppressed by MA supplements. MA would be a
      beneficial nutritional therapy to ameliorate CS-induced lung injury via
      preserving antioxidant defense mechanisms, decreasing oxidative stress and
      inhibiting ER stress, autophagy, apoptosis and emphysema-related risk factor.

PMID- 23122126
TI  - Immunoreactivity of hen egg allergens: influence on in vitro gastrointestinal
      digestion of the presence of other egg white proteins and of egg yolk.
AB  - Hen egg white comprises of a complex mixture of proteins, which greatly differ in
      their physicochemical characteristics and relative abundance. We aimed to
      identify potential undiscovered egg allergens within the egg white proteome and
      investigated the existence of matrix effects on the proteolytic stability and
      resultant IgE-binding of the allergenic proteins. In addition to the main egg
      allergens: ovalbumin (OVA), ovomucoid (OM) and lysozyme (LYS), two minor egg
      white proteins, tentatively identified as ovoinhibitor and clusterin, were found
      to react with serum IgE from egg-allergic patients. Egg white exhibited residual
      immunoreactivity after gastrointestinal digestion due to the presence of intact
      OVA and LYS, as well as of several IgE-binding peptides derived from OVA. The
      presence of egg yolk slightly increased the susceptibility to hydrolysis of egg
      white proteins and abrogated bile salt-induced precipitation of LYS in the
      duodenal medium. However, the resultant immunoreactivity against IgE of egg white
      proteins after in vitro digestion was not significantly modified by the presence
      of yolk components.

PMID- 23122127
TI  - Vitamin C content and sensorial properties of dehydrated carrots blanched
      conventionally or by ultrasound.
AB  - Vitamin C content and sensorial properties have been evaluated in air-dried
      carrots previously subjected to different ultrasound (US) or conventional
      blanching pretreatments. In addition, mass spectral fingerprints obtained by the
      Headspace ChemSensor System have been evaluated for the first time for
      classification of carrots according to their processing. Conventional blanching
      treatments at high temperature gave rise to carrots with retention of vitamin C
      in the range 37.5-85%, whereas carrots blanched conventionally at 60 degrees C
      and by US-probe at temperatures up to 60 and 70 degrees C showed vitamin C
      retention values lower than 4%. Regarding sensorial analysis of rehydrated
      carrots, US-pretreated samples presented acceptable quality, and no statistically
      significant differences with respect to conventionally blanched carrots, were
      detected. In spite of this, differentiation of samples processed under comparable
      intensity conditions and/or with similar composition was possible from their mass
      spectral fingerprints after chemometric data analysis.

PMID- 23122128
TI  - Inhibitory effect of the essential oil of Curcuma longa L. and curcumin on
      aflatoxin production by Aspergillus flavus Link.
AB  - Aflatoxins are highly toxic, mutagenic, teratogenic and carcinogenic mycotoxins.
      Consumption of aflatoxin-contaminated food and commodities poses serious hazards
      to the health of humans and animals. Turmeric, Curcuma longa L., is a native
      plant of Southeast Asia and has antimicrobial, antioxidant and antifungal
      properties. This paper reports the antiaflatoxigenic activities of the essential
      oil of C. longa and curcumin. The medium tests were prepared with the oil of C.
      longa, and the curcumin standard at concentrations varied from 0.01% to 5.0%. All
      doses of the essential oil of the plant and the curcumin standard interfered with
      mycotoxin production. Both the essential oil and curcumin significantly inhibited
      the production of aflatoxins; the 0.5% level had a greater than 96% inhibitory
      effect. The levels of aflatoxin B(1) (AFB(1)) production were 1.0 and 42.7
      MUg/mL, respectively, for the samples treated with the essential oil of C. longa
      L. and curcumin at a concentration of 0.5%.

PMID- 23122129
TI  - Differential sensitivity of D-galactose-binding lectins from fruits of dwarf
      elder (Sambucus ebulus L.) to a simulated gastric fluid.
AB  - Some lectins from Sambucus spp. share amino acid sequences with the pollen Sam n1
      allergen. The lectins ebulin f and SELfd from the early stages of growth were
      isolated and subjected to analysis by MALDI-TOF mass spectrometry, tryptic
      peptide fingerprinting, molecular characterization and pepsin digestibility. The
      molecular mass (33.214) and other structural features of the Sam n1 allergen fit
      best with a monomeric lectin like SELlm (Mr 34.2 kDa) found in shoots of dwarf
      elder. Ebulin f toxicity to mice was higher intraperitoneally than orally at the
      same dose (5mg/kg body weight). In contrast SELfd at the same dose lacks of
      apparent toxicity. Ebulin f, but not SELfd, undergoes extensive pepsin
      proteolysis, which could explain the differences in toxicity. The present study
      supports our hypothesis that the Sam n1 allergen could be a sequence-related
      monomeric lectin like SELlm present in shoots of Sambucus ebulus rather than
      ebulin.

PMID- 23122130
TI  - Total phenolics, antioxidant properties and quality of fresh-cut onions (Allium
      cepa L.) treated with mild-heat.
AB  - This study investigated the effect of mild-heat on fresh-cut onion slices by
      treating in hot water (50, 60, 70 degrees C) for 1 min. Total phenolics (TP),
      antioxidant properties, colour, and weight loss of slices were evaluated during 4
      degrees C storage at 7-day intervals (21 days total). The 60 degrees C heat
      treatment resulted in a significant increase in TP, from 44.92 to 52.32 mg
      GAE/100g. Except for 50 and 70 degrees C treatments, TP in control and 60 degrees
      C treated fresh-cut onions decreased during storage. The antioxidant properties
      of fresh-cut onions were 1.31, 0.99, and 62.49 MUM TE/g using ABTS, DPPH, and
      ORAC assays, respectively. The mild-heat treatments did not affect ABTS and DPPH
      antioxidant activities and the colour of fresh-cut onions. The storage time had
      mixed effect on the antioxidant properties (ABTS decreased; DPPH and ORAC
      remained fairly stable). The 50 degrees C samples exhibited the lowest weight
      loss during 21-day storage.

PMID- 23122131
TI  - Profiles of lipid components, fatty acid distributions of triacylglycerols and
      phospholipids in Jack beans (Canavalia gladiata DC.).
AB  - Endogenous tocopherols in extracted lipids from Jack beans (Canavalia gladiata
      DC.) were determined by high-performance liquid chromatography (HPLC), and were
      investigated in relation to the fatty acids (FA) distribution of triacylgycerols
      (TAG) and phospholipids (PL). The dominant tocopherols were (delta)-tocopherol
      (78.9-96.5mg%) and (gamma)-tocopherol (42.1-56.1mg%) with much smaller amounts of
      (alpha)-tocopherol (1.1-1.3mg%). The lipids of Jack beans comprised mainly TAG
      (34.6-38.6 wt.%) and PL (54.8-57.4 wt.%), and other components were also detected
      in minor proportions (0.3-3.8 wt.%). The PL components included phosphatidyl
      choline (46.2-48.7 wt.%), phosphatidyl inositol (23.4-29.6 wt.%) and phosphatidyl
      ethanolamine (18.5-21.2 wt.%). Comparison of these different beans showed, with a
      few exceptions, no significant differences (P>0.05) in FA distribution. The FA
      distribution of TAG among the five beans was evident in the Jack beans:
      unsaturated FA (93.3-95.3 wt.%) were predominantly concentrated at the sn-2
      position and saturated FA (33.6-34.4 wt.%) primarily occupying the sn-1 position
      or sn-3 position. The results obtained from this work would provide useful
      information to both producers and consumers for manufacturing functional foods or
      beverages in Japan and elsewhere.

PMID- 23122132
TI  - Antidiabetic activity and molecular docking of fructooligosaccharides produced by
      Aureobasidium pullulans in poloxamer-407-induced T2DM rats.
AB  - This study evaluated the beneficial effects of fructooligosaccharide (FOS) intake
      from Aureobasidium pullulans using poloxamer-407 (PX-407) induced type 2 diabetes
      mellitus (T2DM) in rat. Administration of FOS enhanced enzymatic activities of
      catalase and glutathione reductase in a dose-dependent manner. Significant
      reduction in fasting plasma triacylglycerol and very low-density lipoprotein
      level coupled with slight increase in fasting plasma insulin level was observed.
      Significant decrease in severe glucosuria, proteinuria, blood creatinine, urea
      and advanced glycation end products was also observed. Supplementation of FOS
      increased glucagon like peptide-1 content as well as Bifidobacteria and
      Lactobacilli populations in the caecum. Molecular docking by Gold and Glide
      software revealed that three sugar types present in the FOS (1-kestose, nystose,
      and 1-beta-fructofuranosyl nystose) are potent dipeptidyl peptidase-IV inhibitors
      as well as peroxisome proliferator-activated receptor-gamma agonists. This work
      indicates that FOS can be positioned as a nutraceutical product, beneficial in
      diabetes-associated metabolic abnormalities.

PMID- 23122133
TI  - An extract procedure for studying the free and glycosilated aroma compounds in
      grapes.
AB  - In this study seven published methods of extraction of skin free and bound
      volatile compounds have been compared. The free and bound volatiles were
      separated by solid phase extraction (SPE) and then analysed by gas chromatography
      coupled with mass spectrometry (GC-MS). The results showed that the extraction of
      volatile compounds from grapes is highly affected by extraction solution
      features. The solution at pH 3.2 and 0% ethanol resulted the most effective as it
      led to the extraction of a higher number and amount of free and glycosilated
      volatile compounds. The selected extraction method of grape skin and the process
      of pulp juice were validated for quantitative determination of a wide range of
      grape aroma compounds. A total of 37 free and bound grape aroma compounds were
      quantified by GC-MS in selective ion monitoring modality (SIM). Among them, 26
      volatile compounds resulted validated in grape skin and pulp juice.

PMID- 23122134
TI  - Investigation on the phase behaviour of gelatin/agarose mixture in an environment
      of reduced solvent quality.
AB  - Investigation on the phase behaviour of a biopolymer mixture has been performed
      using 7.5% (w/w) gelatin and 1.5% (w/w) agarose in the presence of variable
      amounts of polydextrose as the co-solute from low to high levels of total solids.
      Mechanical observation of the system was performed using small deformation
      dynamic oscillation in shear along with thermal studies using modulated
      differential scanning calorimetry. Micrographs provided images of the changing
      morphology of the network with the addition of co-solute. Agarose and gelatin
      form non-interactive bicontinuous phases in the aqueous environment. Systematic
      increase in the concentration of polydextrose prevents the formation of a stable
      agarose network, with the polysaccharide chains dispersing in the high solids
      environment. Gelatin, on the other hand, retains its conformational stability
      even at a saturating co-solute environment through enhanced protein structuring.
      Vitrification studies on the high solids system at subzero temperatures provides
      information on the structural and molecular relaxation identified as a glass
      transition phenomenon. Fourier transform infrared spectroscopy was used to
      analyse potential direct interaction between polymers and co-solute. The extent
      of amorphicity in the system was confirmed using wide angle X-ray diffraction.

PMID- 23122135
TI  - Identification, characterisation, and quantification of phenolic compounds in the
      antioxidant activity-containing fraction from the seeds of Korean perilla
      (Perilla frutescens) cultivars.
AB  - The present research was the first to investigate phenolic compound profiles and
      antioxidant properties in the seeds of various perilla (Perilla frutescens)
      cultivars. The 80% methanol extract (50 MUg/ml) of this species showed potent
      antioxidant activities against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'
      azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radicals. Phenolic
      compounds were characterised by nuclear magnetic resonance (NMR) spectroscopy,
      and ultra performance liquid chromatography with photodiode array detector and
      electrospray ionisation/mass (UPLC-PDA-ESI/MS) analysis. Nine compounds were
      elucidated as caffeic acid-3-O-glucoside (1), caffeic acid (2), luteolin-7-O
      glucoside (3), apigenin-7-O-glucoside (4), rosmarinic acid-3-O-glucoside (5),
      rosmarinic acid (6), luteolin (7), apigenin (8), and chrysoeriol (9). The
      individual and total phenolic contents were remarkably different, especially
      rosmarinic acid-3-O-glucoside (5) and rosmarinic acid (6) which were the
      predominant compounds (>95%) in all perilla cultivars. Additionally, Yeupsil
      cultivar exhibited the highest phenolic content (5029.0 MUg/g) and antioxidant
      activity, whereas the lowest was shown by Dasil (2138.7 MUg/g). Therefore, these
      results suggest that antioxidant effects of perilla seeds are correlated with
      phenolic contents.

PMID- 23122136
TI  - Degradation kinetics of anthocyanins in acerola pulp: comparison between ohmic
      and conventional heat treatment.
AB  - Degradation kinetics of monomeric anthocyanins in acerola pulp during thermal
      treatment by ohmic and conventional heating was evaluated at different
      temperatures (75-90 degrees C). Anthocyanin degradation fitted a first-order
      reaction model and the rate constants ranged from 5.9 to 19.7 * 10(-3)min(-1).
      There were no significant differences between the rate constants of the ohmic and
      the conventional heating processes at all evaluated temperatures. D-Values ranged
      from 116.7 to 374.5 for ohmic heating and from 134.9 to 390.4 for conventional
      heating. Values of the free energy of inactivation were within the range of
      100.19 and 101.35 kJ mol(-1). The enthalpy of activation presented values between
      71.79 and 71.94 kJ mol(-1) and the entropy of activation ranged from -80.15 to 
      82.63 J mol(-1)K(-1). Both heating technologies showed activation energy of 74.8
      kJ mol(-1) and close values for all thermodynamic parameters, indicating similar
      mechanisms of degradation.

PMID- 23122137
TI  - Hypotriglyceridemic and hypoglycemic effects of vescalagin from Pink wax apple
      [Syzygium samarangense (Blume) Merrill and Perry cv. Pink] in high-fructose diet
      induced diabetic rats.
AB  - Vescalagin, an active component from Pink wax apple [Syzygium samarangense
      (Blume) Merrill and Perry cv. Pink] fruit, with glucose uptake enhancing ability
      in insulin-resistant FL83B mouse hepatocytes, as shown in our previous study, was
      further evaluated for its hypotriglyceridemic and hypoglycemic effects in high
      fructose diet (HFD)-induced diabetic rats. Wistar rats were fed HFD for 16 weeks
      and orally administered with vescalagin from Pink wax apple daily during the last
      4 weeks. The results of biochemical parameters showed that fasting blood glucose,
      C-peptide, fructosamine, triglyceride and free fatty acid contents decreased by
      44.7%, 46.2%, 4.0%, 42.5%, and 10.8%, respectively, in the HFD-induced diabetic
      rats administered with vescalagin at 30 mg/kg body weight in comparison with
      those of control HFD-induced diabetic rats. However, high-density-lipoprotein
      cholesterol content increased by 14.4% in the HFD rats treated with vescalagin.
      The present study reveals that vescalagin could have therapeutic value against
      diabetic progression via its anti-hypertriglyceridemic and anti-hyperglycemic
      effects.

PMID- 23122138
TI  - One-step purification of lactoperoxidase from bovine milk by affinity
      chromatography.
AB  - Sulphanilamide was determined to be a new inhibitor of lactoperoxidase (LPO) with
      an IC(50) of 0.848.10(-5)M. The K(i) for sulphanilamide was determined to be
      3.57.10(-5)M and sulphanilamide showed competitive inhibition, which makes it a
      suitable ligand for constructing a Sepharose 4B-L-tyrosine affinity matrix. The
      affinity matrix was synthesised by coupling sulphanilamide as the ligand and L
      tyrosine as the spacer arm to a cyanogen bromide (CNBr)-activated-Sepharose 4B
      matrix. Lactoperoxidase was purified 409-fold from the synthesized affinity
      matrix in a single step, with a yield of 62.3% and a specific activity of 40.9
      EU/mg protein. The enzyme activity was measured using ABTS as a chromogenic
      substrate (pH 6.0). The degree of LPO purification was monitored by SDS-PAGE and
      its R(z) (A(412)/A(280)) value. The R(z) value for the purified LPO was found to
      be 0.7. Maximum binding was achieved and K(m) and V(max) values were determined.

PMID- 23122139
TI  - Stability and bioaccessibility of different forms of carotenoids and vitamin A
      during in vitro digestion.
AB  - Vitamin A deficiency is a public health issue in developing countries and
      promoting dietary carotenoids as precursors is a promising strategy. However,
      carotenoids present in numerous fruits and vegetables are unstable and poorly
      bioaccessible. This study evaluated these two parameters during in vitro
      digestion of carotenoids and retinoids from carrot juice, raw and cooked spinach,
      micronutrient-fortified flour and standards without food matrix. Standards were
      unstable whereas vitamin A from fortified flour and native food carotenoids were
      generally better protected by the food matrix (30-100% remaining versus 7-30% for
      standards). Hydrothermal cooking did not influence spinach carotenoid digestive
      stability but decreased their contents, phenomenon compensated by a significantly
      better micellarisation from 15-fold for beta-carotene to 72-fold for lutein.
      Finally, carrot juice provided the greatest amount of bioaccessible provitamin A
      with 1850 MUg/100g dry matter (DM) versus 790 and 80 MUg/100g DM in cooked and
      raw spinach, respectively.

PMID- 23122140
TI  - Carotenoid compositions of coloured tomato cultivars and contribution to
      antioxidant activities and protection against H(2)O(2)-induced cell death in
      H9c2.
AB  - The carotenoid compositions, antioxidant activities and the potential cardio
      protective role of 13 tomato cultivars with distinct colour were studied. Colour
      coordinates were evaluated by colorimeter and the carotenoid compositions were
      analysed by UPLC. Red tomatoes had the highest total carotenoid contents (TCC)
      and antioxidant activities, followed by purple, orange, pink and yellow ones. The
      TCC were 120.5-278.0 MUg/gDW, and the antioxidant activities were 21.32-40.07
      MUmolTE/gDW (PCL), 64.42-89.98% (DPPH) and 10.47-13.76 MUmolTE/g DW (ORAC),
      respectively. The lipophilic extracts were also found to prevent cell death in a
      cell-based model system using cardiac H9c2 cells and H(2)O(2), via attenuation of
      the caspase-3 and matrix metalloproteinase-2 activities. The extracts of
      different tomatoes showed strong but different antioxidant activities. Roles of
      total and individual carotenoids in the antioxidant activities were studied and
      lycopene showed the highest correlation. Results of this study can be used to
      guide the development of new tomato cultivars and functional foods, and benefit
      the consumers.

PMID- 23122141
TI  - Medium chain and behenic acid incorporated structured lipids from sal, mango and
      kokum fats by lipase acidolysis.
AB  - Medium chain (MC) and behenic fatty acids were incorporated into kokum, sal and
      mango fats using 1,3-specific lipase catalysed acidolysis. The incorporation of
      fatty acids increased with increase in concentration of fatty acids and duration
      of reaction. The order of incorporation of fatty acids was C22:0>C10:0>C8:0, to
      the extent of 53%, 42.5%, 35.8%, respectively, after 16 h, using kokum as
      substrate. The same trend was observed with sal or mango fats as substrates
      though the percentages incorporated were different. The modified products with
      higher contents of MC were liquids with no solid fats, even at 0 degrees C, and
      which showed low cloud point due to an increase in triacylglycerols containing
      lower chain fatty acids. The modified products after incorporating both MC and
      C22:0 showed long melting ranges and were suitable for use in bakery,
      confectionery, etc. as vanaspati substitutes.

PMID- 23122142
TI  - Application of a qualitative and quantitative real-time polymerase chain reaction
      method for detecting genetically modified papaya line 55-1 in papaya products.
AB  - Genetically modified (GM) papaya (Carica papaya L.) line 55-1 (55-1), which is
      resistant to papaya ringspot virus infection, has been marketed internationally.
      Many countries have mandatory labeling regulations for GM foods, and there is a
      need for specific methods for detecting 55-1. Here, an event- and construct
      specific real-time polymerase chain reaction (PCR) method was developed for
      detecting 55-1 in papaya products. Quantitative detection was possible for fresh
      papaya fruit up to dilutions of 0.001% and 0.01% (weight per weight [w/w]) for
      homozygous SunUp and heterozygous Rainbow cultivars, respectively, in non-GM
      papaya. The limit of detection and quantification was as low as 250 copies of the
      haploid genome according to a standard reference plasmid. The method was
      applicable to qualitative detection of 55-1 in eight types of processed products
      (canned papaya, pickled papaya, dried fruit, papaya-leaf tea, jam, puree, juice,
      and frozen dessert) containing papaya as a main ingredient.

PMID- 23122143
TI  - Physico-chemical changes occurring in oil when atmospheric frying is combined
      with post-frying vacuum application.
AB  - The aim of this study was to investigate the effect of atmospheric frying
      followed by drainage under vacuum on the stability of oil, compared to similar
      frying with drainage at atmospheric pressure. Changes in the oil were assessed by
      the free fatty acid (FFA) content, p-anisidine value (AnV), colour, viscosity,
      fatty acid profile and concentration of tocols. The rate of FFA formation in the
      case of vacuum drainage was found to be about half that of atmospheric drainage.
      Oil deterioration by oxidation and polymerisation was also reduced by the use of
      vacuum drainage. The AnV of the oil after vacuum drainage was lower by about 12%,
      the total colour difference was improved by 14% and viscosity was slightly
      reduced after 5 days of frying, compared to the values for oil that had been
      drained at atmospheric pressure. There was a reduction in the loss of
      polyunsaturated fatty acids in the case of vacuum drainage after 5 days of frying
      but differences in retention of tocols were only evident in the first two days of
      frying.

PMID- 23122144
TI  - Physicochemical properties and tenderness of meat samples using proteolytic
      extract from Calotropis procera latex.
AB  - This study was conducted in order to tenderise muscle foods (pork, beef and
      chicken) by using crude enzyme extract from Calotropis procera latex. Chunks of
      knuckle muscle from pork and beef as well as of breast muscle from chicken were
      marinated with distiled water (control) and 0.05%, 0.1%, 0.2%, 0.3% and 0.5%
      (w/w) of crude enzyme extract powder for 60 min at 4 degrees C. The marinated
      samples were then subjected to various physical and chemical property
      determinations. A decrease in moisture content was observed when the crude enzyme
      extract was added. Firmness and toughness of the muscle samples significantly
      decreased with the increased addition of crude enzyme extract (p<0.05). The water
      holding capacity and cooking yield of the treated samples showed no significant
      difference throughout the crude enzyme extract addition (p>0.05). Crude enzyme
      extract had no effect on the pH of the pork sample, but it slightly increased the
      pH in the beef and chicken. An increase in protein solubility and TCA-soluble
      peptides content was observed in all of the treated samples. The electrophoresis
      pattern of the muscle treated samples also revealed extensive proteolysis
      occurring in each muscle type. From the results, it is determined that latex from
      Calotropis procera can be used as an alternative source of proteolytic enzymes
      for the effective tenderising of meat.

PMID- 23122145
TI  - Comparison of the affinity and selectivity of insoluble fibres and commercial
      proteins for wine proanthocyanidins.
AB  - The fining action of commercial proteins and insoluble fibres for wine
      proanthocyanidin (PA) were compared. Fibres were prepared from fresh apple and
      grape sources, and their corresponding pomaces. PA removal by fibre was via
      adsorption, and required a higher dose to achieve a fining effect comparable with
      proteins. A principal component analysis data model revealed that PA molecular
      mass was significant in defining the fining response, and reflected changes in
      the proportion of the dominant terminal PA subunits catechin and epicatechin, but
      not epicatechin-3-O-gallate. For PA extension subunits, changes in
      epigallocatechin were inversely correlated with epicatechin and epicatechin-3-O
      gallate. Generally, the application of proteins and fibres reduced PA molecular
      mass. Selectivity for PAs by subunit composition was variable between treatments,
      but differences were minor. This work demonstrates the potential use of fibres as
      an alternative to proteins in winemaking. Benefits, and possible limitations of
      such an approach are discussed.

PMID- 23122146
TI  - Impact of microbial transglutaminase on gelling properties of Indian mackerel
      fish protein isolates.
AB  - Impacts of microbial transglutaminase (MTGase) (0-0.6 units/g sample) on gel
      properties of Indian mackerel unwashed mince, surimi and protein isolates with
      and without prewashing were studied. Generally, lower myoglobin and lipid
      contents were found in protein isolate with and without prewashing, compared to
      those of unwashed mince and surimi (P<0.05). Protein isolate had the decreased
      Ca(2+)-ATPase and protein solubility, indicating protein denaturation. When
      MTGase was incorporated, breaking force and deformation of all gels markedly
      increased, especially as MTGase levels increased (P<0.05). At the same MTGase
      level, gel from protein isolate with prewashing exhibited the highest breaking
      force and deformation (P<0.05). The addition of MTGase could lower the
      expressible moisture content of most gels. No change in whiteness of gel was
      observed with the addition of MTGase (P>0.05), but gel from protein isolate gels
      had decreased whiteness as MTGase at high level was added. The microstructure of
      protein isolate gels without prewashing showed a similar network to unwashed
      mince gels, whilst a similar network was observed between surimi gel and gel from
      protein isolate with prewashing. Nevertheless, a larger void was noticeable in
      gels from protein isolates. All gels incorporated with MTGase (0.6 units/g)
      showed a slightly denser network than those without MTGase. Thus, gel with
      improved properties could be obtained from protein isolate from Indian mackerel
      with added MTGase.

PMID- 23122147
TI  - Non-targeted metabolomic approach reveals urinary metabolites linked to steroid
      biosynthesis pathway after ingestion of citrus juice.
AB  - Citrus juice intake has been highlighted because of its health-promoting effects.
      LC-MS based metabolomics approaches are applied to obtain a better knowledge on
      changes in the concentration of metabolites due to its dietary intake and allow a
      better understanding of involved metabolic pathways. Eight volunteers daily
      consumed 400 mL of juice for four consecutive days and urine samples were
      collected before intake and 24h after each citrus juice intake. Urine samples
      were analysed by nanoHPLC-q-TOF, followed by principal component analysis (PCA)
      and Student's t-test (p<0.05). PCA showed a separation between two groups (before
      and after citrus juice consumption). This approach allowed the identification of
      four endocrine compounds (tetrahydroaldosterone-3-glucuronide, cortolone-3
      glucuronide, testosterone-glucuronide and 17-hydroxyprogesterone), which belonged
      to the steroid biosynthesis pathway as significant metabolites upregulated by
      citrus juice intake. Additionally, these results confirmed the importance of
      using the non-targeted metabolomics technique to identify new endogenous
      metabolites, up- or down-regulated as a consequence of food intake.

PMID- 23122148
TI  - Infusion and decoction of wild German chamomile: bioactivity and characterization
      of organic acids and phenolic compounds.
AB  - Natural products represent a rich source of biologically active compounds and are
      an example of molecular diversity, with recognised potential in drug discovery.
      Herein, the methanol extract of Matricaria recutita L. (German chamomile) and its
      decoction and infusion (the most consumed preparations of this herb) were
      submitted to an analysis of phytochemicals and bioactivity evaluation. The
      antioxidant activity was determined by free radicals scavenging activity,
      reducing power and inhibition of lipid peroxidation; the antitumour potential was
      tested in human tumour cell lines (breast, lung, colon, cervical and
      hepatocellular carcinomas), and the hepatotoxicity was evaluated using a porcine
      liver primary cell culture (non-tumour cells). All the samples revealed
      antioxidant properties. The decoction exhibited no antitumour activity
      (GI(50)>400 MUg/mL) which could indicate that this bioactivity might be related
      to compounds (including phenolic compounds) that were not extracted or that were
      affected by the decoction procedure. Both plant methanol extract and infusion
      showed inhibitory activity to the growth of HCT-15 (GI(50) 250.24 and 298.23
      MUg/mL, respectively) and HeLa (GI(50) 259.36 and 277.67 MUg/mL, respectively)
      cell lines, without hepatotoxicity (GI(50)>400 MUg/mL). Infusion and decoction
      gave higher contents of organic acids (24.42 and 23.35 g/100g dw). Otherwise, the
      plant methanol extract contained the highest amounts of both phenolic acids (3.99
      g/100g dw) and flavonoids (2.59 g/100g dw). The major compound found in all the
      preparations was luteolin O-acylhexoside. Overall, German chamomile contains
      important phytochemicals with bioactive properties (mainly antitumour potential
      selective to colon and cervical carcinoma cell lines) to be explored in the
      pharmaceutical, food and cosmetics industries.

PMID- 23122149
TI  - Changes in nitrate and nitrite concentrations over 24h for sweet basil and
      scallions.
AB  - Nitrate and nitrite concentrations were determined for sweet basil and scallions
      over 24h to determine if time of sampling or harvest impacts concentrations in
      raw vegetables. Also, nitrate and nitrite concentrations were determined
      separately for various edible parts of these plants. Basil had significant
      changes in nitrate and nitrite concentrations over a 24h period. Nitrate was
      correlated to changes in light intensity with a 3h lag time. The highest nitrate
      concentrations in basil (2777 ppm) occurred around 3h after the light intensity
      peaked and had low values (165-574 ppm) during the dark period. The scallion
      nitrate and nitrite concentrations were always low but nitrate showed a peak a
      few hours before sunrise. Nitrate and nitrite concentrations in some raw
      vegetables may be reduced by harvesting at the best time of day for each type of
      plant. Nitrate concentrations were different in the edible plant parts tested.

PMID- 23122150
TI  - Authentication of beeswax (Apis mellifera) by high-temperature gas chromatography
      and chemometric analysis.
AB  - Chemical characterization and authentication of beeswax of Apis mellifera was
      performed by high temperature capillary gas chromatography coupled to electron
      impact mass spectrometry or to flame ionisation detection and chemometric
      analysis. Many major components (>50) of beeswax, odd and even hydrocarbons,
      oleofin, palmitate, oleate and hydroxypalmitate monoesters were detected, and for
      the first time palmitate and oleate monoesters esterified with 1-octadecanol and
      1-eicosanol are reported to be present in beeswax. Unsupervised pattern
      recognition procedures, cluster analysis and principal component analysis, were
      used to find data patterns and successfully differentiate authentic and paraffin
      adulterated beeswax based on the chemical profile obtained. Independent
      assessment of beeswax quality and performance of the unsupervised classification
      methods were performed using classical analytical parameters. The discrimination
      power of the chemometric unsupervised methods for detection of paraffin
      adulterated beeswax was superior to the discriminating power of classical
      analytical parameters. Using linear discriminant analysis, classification rules
      for authentic and paraffin adulterated beeswax samples were developed. The model
      was validated by leave-one-out cross validation and showed good recognition and
      prediction abilities, 100% and 99%, respectively.

PMID- 23122151
TI  - Identification of flavonoids and flavonoid rhamnosides from Rhododendron
      mucronulatum for. albiflorum and their inhibitory activities against aldose
      reductase.
AB  - To investigate the therapeutic potential of compounds from natural sources,
      Rhododendron mucronulatum for. albiflorum flowers (RMAF) and R. mucronulatum
      flowers (RMF) were tested for inhibition of aldose reductase (AR). The methanol
      extracts of RMAF and RMF exhibited AR inhibitory activities (IC(50) values 1.07
      and 1.29 MUg/mL, respectively). The stepwise polarity fractions of RMAF were
      tested for in vitro inhibition of AR from rat lenses. Of these, the ethyl acetate
      (EtOAc) fraction exhibited AR inhibitory activity (IC(50) 0.15 MUg/mL). A
      chromatography of the active EtOAc fraction of RMAF led to the isolation of six
      flavonoids, which were identified by spectroscopic analysis as kaempferol (1),
      afzelin (2), quercetin (3), quercitrin (4), myricetin (5) and myricitrin (6).
      Compounds 1-6 exhibited high AR inhibitory activity, with IC(50) values of 0.79,
      0.31, 0.48, 0.13, 11.92 and 2.67 MUg/mL, respectively. HPLC/UV analysis revealed
      that the major flavonoids of RMAF and RMF are quercitrin (4) and myricitrin (6).
      Our results suggest that RMAF containing these six flavonoids could be a useful
      natural source in the development of a novel AR inhibitory agent against diabetic
      complications.

PMID- 23122152
TI  - The influence of the malaxation temperature on the activity of polyphenoloxidase
      and peroxidase and on the phenolic composition of virgin olive oil.
AB  - The effect of the malaxation temperature under sealed conditions on the
      qualitative and quantitative composition of the phenolic compounds in virgin
      olive oils produced from four Italian cultivars was assessed for two atmospheric
      conditions. In both cases, the results show a positive relationship between
      temperature and the concentration of the derivatives of the secoiridoid
      aglycones; the effect of the temperature on the oxidoreductases that promote
      oxidation (polyphenoloxidase and peroxidase) was investigated to determine their
      optimal temperatures and thermal stability. While olive peroxidase (POD) showed
      the highest activity at 37 degrees C and high stability in the temperature range
      tested, polyphenoloxidase (PPO) exhibited the optimum activity at approximately
      50 degrees C, but showed low stability at 40 degrees C, with a large variation in
      stability according to the olive cultivar. These results may contribute to an
      understanding of the increase in the phenol concentration found in virgin olive
      oils obtained following higher temperatures of malaxation.

PMID- 23122153
TI  - Antioxidant activity comparison between [6S]-5-methyltetrahydrofolic acid calcium
      salt and the related racemate form.
AB  - Folates, such as [6S]-5-methyltetrahydrofolic acid, have been introduced in the
      market both in vitamin pills and in fortified foods. Their antioxidant activity
      has been evaluated, but stereoisomer influence on activity has not been proven.
      In this study, a comparison between [6S]-5-methyltetrahydrofolic acid (5-MTHF)
      and its racemate [6R,S] form was made by TEAC assay at different pHs, FRAP assay,
      and ORAC assay. The results showed that the [6S] form had higher antioxidant
      activity than its racemate form in the TEAC assay at all pHs, with similar values
      in the FRAP and ORAC assays. Results suggest that stereoisomeric difference could
      influence the antioxidant activity of 5-MTHF and hence should be taken into
      account when folates are added to foodstuffs to improve their nutritional value.

PMID- 23122154
TI  - Characterisation of kiwifruit and asparagus enzyme extracts, and their activities
      toward meat proteins.
AB  - Two plant enzyme extracts from kiwifruit and asparagus were evaluated for their
      ability to hydrolyse commercially available substrates and proteins present in
      both beef connective tissue and topside myofibrillar extracts. The results show
      significant differences in protease activity depending on the assay used.
      Protease assays with connective tissue and meat myofibrillar extracts provide a
      more realistic evaluation of the potential of the enzymes for application in meat
      tenderization. Overall, the kiwifruit protease extract was found to be more
      effective at hydrolysing myofibrillar and collagen proteins than the asparagus
      protease extract. The two protease extracts appeared to target meat myofibrillar
      and collagen proteins differently, suggesting the potential of a synergistic
      effect of these proteases in improving the tenderness of specific cuts of meat,
      based on their intrinsic protein composition.

PMID- 23122155
TI  - Antidepressant-like effects of fractions, essential oil, carnosol and betulinic
      acid isolated from Rosmarinus officinalis L.
AB  - The aim of this study was to investigate the antidepressant-like effect of
      fractions from Rosmarinus officinalis L.: ethyl acetate 1 and 2 (AcOEt1 and 2),
      hexane (HEX), ethanolic (ET), and essential oil-free (EOF) fractions, as well as
      essential oil, the isolated compounds carnosol and betulinic acid in the tail
      suspension test, a predictive test of antidepressant activity. Swiss mice were
      acutely administered by oral route (p.o.) with fractions, essential oil or
      isolated compounds, 60 min before the tail suspension test or open-field test.
      All of them produced a significant antidepressant-like effect: AcOEt1, ET, EOF
      fractions and essential oil (0.1-100mg/kg, p.o); HEX (0.1-10mg/kg, p.o) and
      AcOEt2 fraction (0.1-1mg/kg, p.o), carnosol (0.01-0.1mg/kg, p.o.) isolated from
      the HEX fraction and betulinic acid (10mg/kg, p.o.), isolated from the AcOEt1 and
      AcOEt2 fractions. No psychostimulant effect was shown in the open-field test,
      indicating that the effects in the tail suspension test are specific. This study
      suggests that carnosol and betulinic acid could be responsible for the anti
      immobility effect of extracts from R. officinalis.

PMID- 23122156
TI  - Use of viscera extract from hybrid catfish (Clarias macrocephalus * Clarias
      gariepinus) for the production of protein hydrolysate from toothed ponyfish
      (Gazza minuta) muscle.
AB  - Proteolytic activity of viscera extract from hybrid catfish (Clarias
      macrocephalus * Clarias gariepinus) was studied. The optimal pH and temperature
      were 9.0 and 50 degrees C, respectively, when toothed ponyfish (Gazza minuta)
      muscle was used as a substrate. When viscera extract from hybrid catfish was used
      for the production of protein hydrolysate from toothed ponyfish muscle, extract
      concentration, reaction time, and fish muscle/buffer ratio affected the
      hydrolysis and nitrogen recovery (NR) (p<0.05). Optimum conditions for toothed
      ponyfish muscle hydrolysis were 3.5% hybrid catfish viscera extract, 15 min
      reaction time and fish muscle/buffer ratio of 1:3 (w/v). High correlation between
      the degree of hydrolysis (DH) and NR (R(2)=0.974) was observed. Freeze-dried
      hydrolysate had a high protein content (89.02%, dry weight basis) and it was
      brownish yellow in colour (L(*)=63.67, a(*)=6.33, b(*)=22.41). The protein
      hydrolysate contained a high amount of essential amino acids (48.22%) and had
      arginine and lysine as the dominant amino acids.

PMID- 23122157
TI  - Encapsulation of food grade antioxidant in natural biopolymer by electrospinning
      technique: a physicochemical study based on zein-gallic acid system.
AB  - Gallic acid was successfully incorporated into zein ultra-fine fibres at
      different loading amount (5%, 10% and 20%) in order to develop an encapsulating
      technology for functional ingredient delivery using electrospinning. The produced
      fibres exhibit diameters ranging from 327 to 387 nm. The physical and thermal
      properties of encapsulated gallic acid were determined by X-ray diffraction (XRD)
      and differential scanning calorimetry (DSC); and the interaction between gallic
      acid and zein was attested by attenuated total reflection-Fourier transform
      infrared (ATR-FTIR). Thermogravimetric analysis (TGA) demonstrated a different
      thermal stability of the fabricated complex before and after the gallic acid
      incorporation. Lastly, the 1,1'-diphenyl-2-picrylhydrazyl (DPPH) assay showed
      that the gallic acid had retained its antioxidant activity after incorporation in
      zein electrospun fibres. Overall, electrospinning technique had shown promising
      results as an efficient and effective method for the preparation of sub-micron
      structured encapsulated functional ingredient that may find uses in food
      industry.

PMID- 23122158
TI  - Simultaneous separation and purification of total polyphenols, chlorogenic acid
      and phlorizin from thinned young apples.
AB  - An efficient preparative separation of polyphenols from thinned young apples
      (TYA) has been developed in the present study. X-5 resin was verified to offer
      the best adsorption capacity and desorption ratio for total polyphenols among the
      eight macroporous resins investigated. Influential factors, such as pH value and
      concentration of feeding solution, strippant, and adsorption isotherm to the
      separation of total polyphenols, were successively investigated on X-5 resin.
      After one run treatment, the phenolic content was increased 2.12-fold from 35.17%
      to 74.64%, with a recovery yield of 89.35%. Chlorogenic acid and phlorizin were
      selectively purified using X-5 and polyamide resins. The contents of chlorogenic
      acid and phlorizin were 15.20% and 97.52% with recovery yields of 89.16% and
      64.95%, respectively. The method developed will provide a potential approach for
      its wide industrial and pharmaceutical use.

PMID- 23122159
TI  - Antioxidant and antihypertensive properties of liquid and solid state fermented
      lentils.
AB  - The effect of liquid (LSF) and solid state fermentation (SSF) of lentils for
      production of water-soluble fractions with antioxidant and antihypertensive
      properties was studied. LSF was performed either spontaneously (NF) or by
      Lactobacillus plantarum (LP) while SSF was performed by Bacillus subtilis (BS).
      Native lactic flora in NF adapted better than L. plantarum to fermentative broth
      and BS counts increased 4.0 logCFU/g up to 48 h of SSF. LSF water-soluble
      fractions had higher (P <= 0.05) free amino groups, GABA content, antioxidant and
      angiotensin I-converting enzyme inhibitory (ACEI) activities than SSF. In
      addition, GABA and ACEI activity of LSF increased in a time-dependent manner.
      Proteolysis by BS was limited, with slight changes in free amino groups, while
      GABA, total phenolic compounds and antioxidant capacity increased throughout
      fermentation. Higher antihypertensive potential was observed in NF (96 h)
      characterised by the highest GABA content (10.42 mg/g extract), ACE-inhibitory
      potency (expressed as IC(50)) of 0.18 mg protein/ml and antioxidant capacity of
      0.26 mmol Trolox equivalents/g extract. Therefore, water-soluble fermented lentil
      extracts obtained by LSF are particularly promising as functional ingredients in
      preventing hypertension.

PMID- 23122160
TI  - Feasibility and application of an HPLC/UVD to determine dinotefuran and its
      shorter wavelength metabolites residues in melon with tandem mass confirmation.
AB  - A new analytical method was developed for dinotefuran and its metabolites, MNG,
      UF, and DN, in melon using high-performance liquid chromatography (HPLC) coupled
      with an ultraviolet detector (UVD). Due to shorter wavelength, lower sensitivity
      to UV detection, and high water miscibility of some metabolites, QuEChERs acetate
      buffered version was modified for extraction and purification. Mobile phases with
      different ion pairing or ionisation agents were tested in different reverse phase
      columns, and ammonium bicarbonate buffer was found as the best choice to increase
      the sensitivity of target analytes to the UV detector. After failure of
      dispersive SPE clean-up with primary secondary amine, different solid phase
      extraction cartridges (SPE) were used to check the protecting capability of
      analytes against matrix interference. Finally, samples were extracted with a
      simple and rapid method using acetonitrile and salts, and purified through
      C(18)SPE. The method was validated at two spiking levels (three replicates for
      each) in the matrix. Good recoveries were observed for all of the analytes and
      ranged between 70.6% and 93.5%, with relative standard deviations of less than
      10%. Calibration curves were linear over the calibration ranges for all the
      analytes with r(2)>= 0.998. Limits of detection ranged from 0.02 to 0.05 mg kg(
      1), whereas limits of quantitation ranged from 0.06 to 0.16 mg kg(-1) for
      dinotefuran and its metabolites. The method was successfully applied to real
      samples, where dinotefuran and UF residues were found in the field-incurred melon
      samples. Residues were confirmed via LC-tandem mass spectrometry (LC-MS/MS) in
      positive-ion electrospray ionisation (ESI(+)) mode.

PMID- 23122161
TI  - Suppression of LPS-induced inflammatory activities by Rosmarinus officinalis L.
AB  - Rosemary (Rosmarinus officinalis L.) has been used in folk medicine to treat
      headaches, epilepsy, poor circulation, and many other ailments. It was found that
      rosemary could act as a stimulant and mild analgesic and could reduce
      inflammation. However, the mechanisms underlying the anti-inflammatory effects of
      rosemary need more study to be established. Therefore, in this study, the effects
      of rosemary on the activation of nuclear factor kappa beta (NF-kB) and mitogen
      activated protein kinases (MAPKs), the expression of inducible nitric oxide
      synthase (iNOS) and cyclooxygenase-2 (COX-2), and the production of nitric oxide
      (NO), prostaglandin E(2) (PGE(2)), and cytokine in lipopolysaccharide (LPS)
      stimulated RAW 264.7 cells were investigated. A methanol extract of rosemary and
      its hexane fraction reduced NO generation with an IC(50) of 2.75 and 2.83 MUg/ml,
      respectively. Also, the methanol extract and the hexane fraction inhibited LPS
      induced MAPKs and NF-kB activation associated with the inhibition of iNOS or COX
      2 expression. LPS-induced production of PGE(2) and tumour necrosis factor-alpha
      (TNF-alpha) were blocked by rosemary. Rosemary extract and its hexane fraction
      are important for the prevention of phosphorylation of MAPKs, thereby blocking NF
      kB activation, which in turn leads to decreased expression of iNOS and COX-2,
      thus preventing inflammation.

PMID- 23122162
TI  - Fucoxanthin content and antioxidant properties of Undaria pinnatifida.
AB  - This study investigated the fucoxanthin content of New Zealand (NZ) Undaria
      pinnatifida harvested from two locations in the Marlborough Sounds, New Zealand
      across its growing season. Fucoxanthin content and antioxidant properties of
      processed New Zealand U. pinnatifida and commercial wakame from Japan and Korea
      were further compared. Results showed that U. pinnatifida harvested from Port
      Underwood had higher fucoxanthin content in the blade compared to Pelorus Sound.
      The sporophyll also contained a significant amount of fucoxanthin throughout the
      harvest season, although lower than in the blade. Two antioxidant measurement
      methods, DPPH and CUPRAC, were utilised to measure antioxidant activities.
      Processed NZ U. pinnatifida had a lower fucoxanthin content and antioxidant
      activity than freeze-dried Undaria. Fucoxanthin content and antioxidant
      activities of NZ processed U. pinnatifida were not significantly different from
      other commercial samples from Japan and Korea. In conclusion, U. pinnatifida in
      New Zealand has a great potential to be a food and nutraceutical resource.

PMID- 23122163
TI  - Reverse micellar extraction of bovine serum albumin - a comparison between the
      effects of gemini surfactant and its corresponding monomeric surfactant.
AB  - Gemini surfactant displayed distinct advantages over monomeric surfactant in the
      liquid-liquid reverse micellar extraction process. First, less amount of gemini
      surfactant than monomeric surfactant was needed for transferring almost complete
      bovine serum albumin (BSA) into organic phase from aqueous phase. Second, the
      loading capacity of gemini surfactant reverse micelle phase was much higher than
      that of the corresponding monomeric surfactant reverse micelle. Third, efficient
      backward extraction (75-92%) of BSA could be effected in a wide pH range from 4
      to 9 with gemini surfactant reverse micelle while a pH of ca. 4.3 is prerequisite
      to the recovery of BSA from monomeric surfactant reverse micelle. So far, the
      reports about the effect of surfactant structure on protein extraction have been
      limited. This study indicates the important role of the spacer of gemini
      surfactant in protein extraction process and may provide more knowledge on how to
      optimise surfactant structure.

PMID- 23122164
TI  - Structure and composition of model cheeses influence sodium NMR mobility,
      kinetics of sodium release and sodium partition coefficients.
AB  - The mobility and release of sodium ions were assessed in model cheeses with three
      different lipid/protein ratios, with or without added NaCl. The rheological
      properties of the cheeses were analysed using uniaxial compression tests.
      Microstructure was characterised by confocal laser scanning microscopy. (23)Na
      nuclear magnetic resonance (NMR) spectroscopy was used to study the molecular
      mobility of sodium ions in model cheeses through measurements of the relaxation
      and creation times. Greater mobility was observed in cheeses containing a lower
      protein content and with added NaCl. The kinetics of sodium release from the
      cheese to an aqueous phase was correlated with the mobility of sodium ions. The
      highest rates of sodium release were observed with a lower protein content and
      with added NaCl. The water/cheese partition coefficients of sodium increased when
      NaCl was added or the protein content was higher. The study highlighted the
      effect of model cheese characteristics on molecular and macroscopic behaviours of
      sodium.

PMID- 23122165
TI  - Occurrence and sensory perception of Z-2-(beta-d-glucopyranosyloxy)-3
      phenylpropenoic acid in rooibos (Aspalathus linearis).
AB  - Z-2-(beta-d-glucopyranosyloxy)-3-phenylpropenoic acid (PPAG), a compound
      postulated to contribute to the taste and mouthfeel of fermented rooibos tea
      (Aspalathus linearis), was isolated from unfermented rooibos plant material. Its
      structure was unequivocally confirmed by LC-MS, -MS(2), FT-IR and NMR of the
      underivatised natural product, and optical rotation measurements of the
      hydrolysed sugar moiety. A similar compound, postulated to be E-2-(beta-d
      glucopyranosyloxy)-3-phenylpropenoic acid, was also detected. Analysis of the
      leaves of a large number of rooibos plants (n=54), sampled at commercial
      plantations, showed that PPAG is not ubiquitously present in detectable
      quantities in the leaves of different plants. This leads to large variation in
      the fermented plant material, infusions and food-grade extracts. PPAG was shown
      to have a slightly bitter to astringent taste and a detection threshold of 0.4
      mg/l in water.

PMID- 23122166
TI  - Reduction of lipid accumulation in white adipose tissues by Cassia tora
      (Leguminosae) seed extract is associated with AMPK activation.
AB  - Natural herbal medications may be one answer to the worldwide epidemic of
      obesity. This study examines the effects of Cassia seed ethanol extract (CSEE)
      upon lipid accumulation in white adipose tissue (WAT). CSEE exhibited a
      significant concentration-dependent decrease in the intracellular accumulation of
      trigycerides in 3T3-L1 adipocytes. After being fed a high-fat diet (HFD) for 2
      weeks, rats were fed CSEE (100, 200 or 300 mg/kg) once daily for 8 weeks. CSEE
      caused dose-related reductions in body weight gain (as well as plasma lipid
      levels and epididymal WAT sizes in HFD-fed rats). CSEE enhanced the
      phosphorylation of AMP-activated protein kinase (AMPK) and its primary downstream
      targeting enzyme, acetyl-CoA carboxylase, up-regulated gene expression of
      carnitine palmitoyl transferase 1, and down-regulated sterol regulatory element
      binding protein 1 and fatty acid synthase protein levels in epididymal WAT of HFD
      fed rats. CSEE could attenuate lipid accumulation in WAT via AMPK signaling
      pathway activation.

PMID- 23122167
TI  - Schisarisanlactones A and B: a new class of nortriterpenoids from the fruits of
      Schisandra arisanensis.
AB  - Two novel highly oxygenated nortriterpenoids, schisarisanlactones A (1) and B
      (2), have been isolated from the fruits of Schisandra arisanensis, an endemic
      plant of Taiwan. Compounds 1 and 2 possess an unprecedented 5/5/7/5/5-fused
      pentacyclic ring system. The structures of both compounds were determined on the
      basis of spectroscopic analyses, especially 2D NMR and MS. A plausible biogenetic
      pathway of 1 was proposed. Schisarisanlactone A (1) showed significant anti-HIV
      activity.

PMID- 23122168
TI  - Optimisation of resistant starch II and III levels in durum wheat pasta to reduce
      in vitro digestibility while maintaining processing and sensory characteristics.
AB  - Foods with elevated levels of resistant starch (RS) may have beneficial effects
      on human health. Pasta was enriched with commercial resistant starches (RSII, Hi
      MaizeTM 1043; RSIII, Novelose 330TM) at 10%, 20% and 50% substitution of semolina
      for RSII and 10% and 20% for RSIII and compared with pasta made from 100% durum
      wheat semolina to investigate technological, sensory, in vitro starch
      digestibility and structural properties. The resultant RS content of pasta
      increased from 1.9% to ~21% and was not reduced on cooking. Significantly, the
      results indicate that 10% and 20% RSII and RSIII substitution of semolina had no
      significant effects on pasta cooking loss, texture and sensory properties, with
      only a minimal reduction in pasta yellowness. Both RS types lowered the extent of
      in vitro starch hydrolysis compared to that of control pasta. X-ray diffraction
      and small-angle scattering verified the incorporation of RS and, compared to the
      control sample, identified enhanced crystallinity and a changed molecular
      arrangement following digestion. These results can be contrasted with the
      negative impact on pasta resulting from substitution with equivalent amounts of
      more traditional dietary fibre such as bran. The study suggests that these RS
      containing formulations may be ideal sources for the preparation of pasta with
      reduced starch digestibility.

PMID- 23122169
TI  - Abietane diterpenoids from Isodon lophanthoides var. graciliflorus and their
      cytotoxicity.
AB  - Seven new (1-7) and three known (8-10) abietane diterpenoids were isolated from
      the methanolic extract of the aerial parts of Isodon lophanthoides var.
      graciliflorus (Lamiaceae), a folk Chinese medicine and an herb for functional
      beverages. They were identified as 16-acetoxylsugiol (1), graciliflorin E (2),
      graciliflorin F (3), 15-O-methylgraciliflorin F (4), 15-hydroxy-20-deoxocarnosol
      (5), 3beta-hydroxysempervirol (6), 15-hydroxy-1-oxosalvibretol (7), abieta
      8,11,13-triene-14,19-diol (8), 6,12,15-trihydroxy-5,8,11,13-abietatetraen-7-one
      (9), and 3alpha-hinokiol (10) based on the spectroscopic data including COSY
      (correlated spectroscopy), HMBC (heteronuclear multiple bond correlation), and HR
      ESI-MS (high-resolution electrospray ionization mass spectrometry). All the
      compounds except 10 were obtained from I. lophanthoides for the first time.
      Compounds 1, 2, 5, 6, 8, and 9 exhibited in vitro cytotoxicity against A549
      (human lung adenocarcinoma), MCF-7 (human breast adenocarcinoma), and HeLa (human
      cervical carcinoma) cell lines with the IC(50) values of 1.79-52.67 MUM.

PMID- 23122170
TI  - Bridging the know-do gap in health care through integrated knowledge translation.

PMID- 23122171
TI  - Practical otic anatomy and physiology of the dog and cat.
AB  - Knowledge of the normal structure and function of the canine and feline ear is
      critical to be able to diagnose abnormalities that either involve the ear or
      originate within one or more of the ear compartments. In addition, a veterinarian
      must be aware of various structures within or associated with the ear so that
      they are not damaged or destroyed while treating an animal with otic disease.
      This article provides a brief discussion of the various anatomic features of the
      ear and normal physiology of portions of the ear.

PMID- 23122172
TI  - Collection and preparation of dog and cat ears for histologic examination.
AB  - Most veterinary textbooks provide very little guidance regarding ear sampling,
      processing, and examination. The complexity of the ear, which includes
      integument, mucosa, cartilage, bone, and neural tissues, and the special
      procedures required to allow histologic examination are 2 of the more common
      reasons for reluctance by clinicians and pathologists to thoroughly assess the
      ear. This article helps demystify both the collection and preparation of ear
      samples, and briefly describes gross features and key landmarks of the ear.
      However, it is not the intent to provide an exhaustive account of normal and
      pathologic findings.

PMID- 23122173
TI  - Primary secretory otitis media in Cavalier King Charles spaniels.
AB  - Primary secretory otitis media (PSOM) is a disease that has been described in the
      Cavalier King Charles spaniel (CKCS). A large, bulging pars flaccida identified
      on otoscopic examination confirms the diagnosis. However, in many CKCS with PSOM
      the pars flaccida is flat, and radiographic imaging is needed to confirm the
      diagnosis. Current treatment for PSOM includes performing a myringotomy into the
      caudal-ventral quadrant of the pars tensa with subsequent flushing of the mucus
      out of the bulla using a video otoscope. Repeat myringotomies and flushing of the
      middle ear are necessary to keep the middle ear free of mucus.

PMID- 23122174
TI  - Neurological manifestations of ear disease in dogs and cats.
AB  - There are four major neuroanatomical structures associated with the ear that,
      when damaged, result in different neurologic clinical signs. These structures are
      the facial nerve, the ocular sympathetic tract, the vestibular receptors, and the
      cochlea. The clinical signs associated with disorders of each structure are
      discussed, followed by a summary of the diseases that should be considered in
      each case. The article begins with a description of the neuroanatomy of each of
      these structures.

PMID- 23122175
TI  - Tumors and tumorlike lesions of dog and cat ears.
AB  - Bacterial and fungal otitis constitutes most ear disease in companion animals.
      However, a wide spectrum of infectious and noninfectious disease processes
      involve the structures of the ear and are of primary diagnostic consideration in
      cases of recurrent otitis or those refractive to traditional treatments. This
      article discusses several common to reasonably rare neoplastic and nonneoplastic
      space-occupying lesions of the external, middle, and internal ear. Although some
      conditions present as unique entities, many present similar to or concurrent with
      otitis, and should be considered in cases of clinically unresponsive otitis.

PMID- 23122177
TI  - Canine deafness.
AB  - Conductive deafness, caused by outer or middle ear obstruction, may be corrected,
      whereas sensorineural deafness cannot. Most deafness in dogs is congenital
      sensorineural hereditary deafness, associated with the genes for white pigment:
      piebald or merle. The genetic cause has not yet been identified. Dogs with blue
      eyes have a greater likelihood of hereditary deafness than brown-eyed dogs. Other
      common forms of sensorineural deafness include presbycusis, ototoxicity, noise
      induced hearing loss, otitis interna, and anesthesia. Definitive diagnosis of
      deafness requires brainstem auditory evoked response testing.

PMID- 23122178
TI  - Canine hearing loss management.
AB  - Dog owners and handlers are naturally concerned when suspicion of hearing loss
      arises for their dogs. Questions frequently asked of the veterinarian center on
      warning signs of canine hearing loss and what can be done for the dog if hearing
      loss is confirmed. This article addresses warning signs of canine hearing loss,
      communication training and safety awareness issues, and the feasibility of
      hearing aid amplification for dogs.

PMID- 23122179
TI  - Electrodiagnostic evaluation of auditory function in the dog.
AB  - Given the high incidence of deafness within several breeds of dogs, accurate
      hearing screening and assessment is essential. In addition to brainstem auditory
      evoked response (BAER) testing, 2 other electrophysiologic tests are now being
      examined as audiologic tools for use in veterinary medicine: otoacoustic
      emissions and the auditory steady state response (ASSR). To improve BAER testing
      of animals and ensure an accurate interpretation of test findings from one test
      site to another, the establishment of and adherence to clear protocols is
      essential. The ASSR holds promise as an objective test for rapid testing of
      multiple frequencies in both ears simultaneously.

PMID- 23122176
TI  - Feline deafness.
AB  - Cats have among the best hearing of all mammals in that they are extremely
      sensitive to a broad range of frequencies. The ear is a highly complex structure
      that is delicately balanced in terms of its biochemistry, types of receptors, ion
      channels, mechanical properties, and cellular organization. Sensorineural
      deafness is caused by "flawed" genes that are inherited from one or both parents.
      Hearing loss can also be acquired as a result of noise trauma from industrialized
      environment, viral infection, or blunt trauma. To date, it is not practical to
      intervene and attempt to correct these forms of deafness in cats.

PMID- 23122180
TI  - Ototoxicity in dogs and cats.
AB  - A variety of drugs in veterinary use have side effects that can potentially
      damage the senses of hearing or balance in animals. A large body of literature
      exists on the incidence and mechanisms of ototoxicity in experimental animals and
      in humans, but little is documented in domestic dogs and cats. However, the
      generality of these adverse actions across species allows one to extrapolate and
      provide the veterinarian with insight into possible complications of
      chemotherapy.

PMID- 23122181
TI  - Otology and otic diseases.

PMID- 23122183
TI  - Outcomes of endovascular aneurysm repair in patients with hostile neck anatomy.
AB  - OBJECTIVES: This study aims to evaluate outcomes following EVAR in patients with
      hostile neck anatomy (HNA). METHODS: Data prospectively collected from 552
      elective EVARs were analysed retrospectively. Data regarding neck morphology was
      obtained from aneurysm stent plans produced prior to EVAR. HNA was defined as any
      of; neck diameter >28 mm, neck angulation >60 degrees , neck length <15 mm, neck
      thrombus, or neck flare. RESULTS: 552 patients underwent EVAR. Mean age 73.9
      years, mean follow-up 4.1 years. 199 patients had HNA, 353 had favourable neck
      anatomy (FNA). There was a significant increase in late type I endoleaks (FNA
      4.5%, HNA 9.5%; P = 0.02) and total reinterventions (FNA 11.0%, HNA 22.8%; P <
      0.01), and a significant decrease in late type II endoleaks in patients with HNA
      (FNA 16.7%, HNA 10.6%; P < 0.05). There was no significant difference in
      technical success (FNA 0.6%, HNA 2.0%; p = 0.12), 30-day re-intervention (FNA
      2.8%, HNA 5.0%; P = 0.12), 30-day mortality (FNA 1.1%, HNA 0.5%; P = 0.45), 30
      day type I endoleaks (FNA 0.8%, HNA 2.5%; P = 0.12), 5-year mortality (FNA 15.1%,
      HNA 14.6%; P = 0.86), aneurysm-related mortality (FNA 1.7% versus HNA 2.0%; P =
      0.79), stent-graft migration (FNA 2.5%, HNA 3.0%; P = 0.75), sac expansion (FNA
      13.0%, HNA 9.5%; P = 0.22), or graft rupture (FNA 1.1%, HNA 3.5%; P = 0.05).
      Binary logistic regression of individual features of HNA revealed secondary
      intervention (P = 0.009), technical failure (P = 0.02), and late type I endoleaks
      (P = 0.002), were significantly increased with increased neck diameter.
      CONCLUSIONS: HNA AAAs can be successfully treated with EVAR. However,
      surveillance is necessary to detect and treat late type I endoleaks in HNA
      patients.

PMID- 23122184
TI  - Randomised diagnostic accuracy study of a fully automated portable device for
      diagnosing peripheral arterial disease by measuring the toe-brachial index.
AB  - OBJECTIVE: To assess the accuracy of a fully automated portable device (APD) for
      diagnosing peripheral arterial disease (PAD) by measuring the toe-brachial index
      (TBI) and using mercury-in-silastic, strain-gauge plethysmography (SGP) as
      reference. DESIGN: Prospective, randomised, double-blinded diagnostic accuracy
      study. MATERIALS AND METHODS: A total of 204 consecutive patients with known or
      suspected PAD were randomly assigned to measurement of TBI by the portable device
      followed by the SGP technique or the opposite sequence. Finally, ankle-brachial
      index (ABI) was assessed by SGP. RESULTS: The APD showed a sensitivity of 98.8%,
      a specificity of 61.0%, a positive predictive value of 91.0% and a negative
      predictive value of 92.6% for detecting PAD compared to a full SGP test comprised
      of ABI and TBI. According to the SGP test, 35 patients (17.2%) had an ABI > 0.90
      but a TBI < 0.70. Correlation analysis of the absolute toe pressures by the two
      methods showed an intraclass correlation coefficient of 0.937 (95% confidence
      interval (CI) 0.887-0.962) for right toe pressures and 0.939 (95% CI 0.908-0.958)
      for the left toe pressures. CONCLUSIONS: The APD showed excellent diagnostic test
      characteristics for detecting PAD compared to SGP. Furthermore, the APD had a
      good correlation in absolute toe pressures with SGP.

PMID- 23122182
TI  - Novel molecular, cytotoxical, and immunological study on promising and selective
      anticancer activity of mung bean sprouts.
AB  - BACKGROUND: The anticancer and immunomodulatory activity of mung bean sprouts
      (MBS) and the underlying mechanisms against human cervical and hepatocarcinoma
      cancer cells were explored. METHODS: MBS cytotoxicity and MBS-induced anticancer
      cytokines, TNF-alpha and IFN-beta from cancer cells, and immunological cytokines,
      IL-4, IFN-gamma, and IL-10 from peripheral mononuclear cells (PMNC) were assessed
      by MTS and ELISA assays. Apoptotic cells were investigated by flow cytometry. The
      expression level of apoptotic genes (Bax, BCL-2, Capsases 7-9) and cell cycle
      regulatory genes (cyclin D, E, and A) and tumor suppressor proteins (p27, p21,
      and p53) was assessed by real-time qPCR in the cancer cells treated with extract
      IC50. RESULTS: The cytotoxicity on normal human cells was significantly different
      from HeLa and HepG2 cells, 163.97 +/- 5.73, 13.3 +/- 0.89, and 14.04 +/- 1.5
      mg/ml, respectively. The selectivity index (SI) was 12.44 +/- 0.83 for HeLa and
      11.94 +/- 1.2 for HepG2 cells. Increased levels of TNF-alpha and IFN-beta were
      observed in the treated HeLa and HepG2 culture supernatants when compared with
      untreated cells. MBS extract was shown to be an immunopolarizing agent by
      inducing IFNgamma and inhibiting IL-4 production by PBMC; this leads to
      triggering of CMI and cellular cytotoxicity. The extract induced apoptosis, in a
      dose and time dependent manner, in treated HeLa and HepG2, but not in untreated,
      cells (P < 0.05). The treatment significantly induced cell cycle arrest in G0/G1
      in HeLa cells. The percentage of cells in G0/G1 phase of the treated HeLa cells
      increased from 62.87 +/- 2.1%, in untreated cells, to 80.48 +/- 2.97%.
      Interestingly, MBS IC50 induced the expression of apoptosis and tumor suppressor
      related genes in both HeLa and HepG2 cells. MBS extract succeeded in inducing cdk
      inhibitors, p21, p53, and p27 in HeLa cells while it induced only p53 in HepG2
      cells (P < 0.05). This is a clue for the cell type- specific interaction of the
      studied extract. These proteins inhibit the cyclin-cdk complexes apart from the
      presence of some other components that might stimulate some cyclins such as
      cyclin E, A, and D. CONCLUSION: MBS extract was shown to be a potent anticancer
      agent granting new prospects of anticancer therapy using natural products.

PMID- 23122185
TI  - Evaluation of the minimum effective concentration of foam sclerosant in an ex
      vivo study.
AB  - BACKGROUND: Foam sclerosants are widely used in sclerotherapy and have been
      accepted as more effective than the liquid form; however, there is no consensus
      about the most applicable and effective concentration. OBJECTIVE: The aim of this
      study was to investigate the histopathological changes caused by various widely
      used concentrations of foam sclerosant. METHODS: Fifty-six varicose vein segments
      of 5-10 mm diameter were gently resected and exposed to various concentrations of
      foam sclerosant (0.5%, 1%, 2%, 3%) for 5 min, and were then prepared for routine
      histopathological examination. A total damage scoring system, including the
      presence of endothelial swelling, intimal thickening, cellular vacuolization in
      the muscle layer, edema in the tunica media and extent of necrosis, was
      established. RESULTS: The total damage score of the foam sclerosant groups was
      significantly higher than that of the control group (median 2.75 vs 1, p =
      0.007). The highest damage score was achieved by 1% and 2% foam sclerosants (3.5
      and 2.5). No significant difference was found among the different concentrations
      of sclerosant, although the 1% group caused more severe damage at a near
      significant level (p = 0.074). CONCLUSION: Significant pathological damage can be
      caused by even the lowest doses of foam sclerosant. The most injurious
      concentrations were found to be 1% and 2%, morphologically. A working
      concentration of 1% could thus be preferable to 0.5%, especially in larger veins.
      Further in-vivo studies are needed in order to validate these findings.

PMID- 23122186
TI  - Does occupational driving increase the risk of cardiovascular disease in people
      with diabetes?
AB  - Occupational driving may increase cardiovascular events. We studied the risk of
      overall cardiovascular events in occupational professional drivers against
      matched controls in a cohort of people with diabetes (N=6563). There was an
      increase in overall cardiovascular events in occupational drivers despite similar
      risk factors. This particular occupational risk factor may need to be addressed.

PMID- 23122187
TI  - Italian Biological Prosthesis Work-Group (IBPWG): proposal for a decisional model
      in using biological prosthesis.
AB  - INTRODUCTION: Indications for repair of abdominal hernia are well established and
      widely diffused. Controversies still exist about the indication in using the
      different prosthetic materials and principally about the biological ones.
      MATERIAL AND METHODS: In February 2012, the Italian Biological Prosthesis Work
      Group (IBPWG), counting a background of 264 biologic implants, met in Bergamo
      (Italy) for 1-day meeting with the aim to elaborate a decisional model on
      biological prosthesis use in abdominal surgery. RESULTS: A diagram to simplify
      the decisional process in using biologics has been elaborated. CONCLUSION: The
      present score represents a first attempt to combine scientific knowledge and
      clinical expertise in order to offer precise indications about the kind of
      biological mesh to use.

PMID- 23122188
TI  - A direct comparison of endothelial progenitor cell dysfunction in rat metabolic
      syndrome and diabetes.
AB  - OBJECTIVES: Diabetes mellitus (DM) is associated with impairment of endothelial
      progenitor cells (EPCs), but the effects of metabolic syndrome (MS) on EPCs have
      been less well characterized. We hypothesized that in the presence of MS, the
      number and functionality of EPCs would be markedly reduced, and would be similar
      to DM. METHODS: Mononuclear cells were isolated from the bone-marrow (BM) and
      peripheral blood of lean Zucker, obese Zucker, a model of MS, and Zucker diabetic
      fatty rats. Cultured BM-EPCs underwent in vitro functional testing and the
      ability of BM-EPCs to promote neovascularization in vivo was assessed in a model
      of hindlimb ischemia in athymic mice. RESULTS: While circulating EPC numbers were
      similarly reduced in both MS and DM rats, BM-derived EPC numbers were less
      affected. In vitro testing of cultured BM-EPCs from obese Zucker demonstrated a
      marked reduction in EPC differentiation, a greater propensity to apoptosis, a
      reduced migratory response and matrigel tubule formation, similar to findings in
      Zucker diabetic fatty rats. When delivered to the ischemic hindlimb of athymic
      mice, the recovery of perfusion using both BM-EPCs from obese Zucker and Zucker
      diabetic fatty rats were diminished, as compared to lean Zuckers. CONCLUSION: In
      the presence of the MS, BM-derived EPCs develop marked functional impairment,
      resulting in severely reduced angiogenic capacity in vivo. Similar to DM, EPC
      dysfunction may play a prominent role in the pathogenesis of vascular
      complications in the MS, and may potentially limit the use of BM-derived EPCs for
      therapeutic angiogenesis.

PMID- 23122189
TI  - Statistical estimates of respiratory admissions attributable to seasonal and
      pandemic influenza for Canada.
AB  - BACKGROUND: The number of admissions to hospital for which influenza is
      laboratory confirmed is considered to be a substantial underestimate of the true
      number of admissions due to an influenza infection. During the 2009 pandemic,
      testing for influenza in hospitalized patients was a priority, but the
      ascertainment rate remains uncertain. METHODS: The discharge abstracts of persons
      admitted with any respiratory condition were extracted from the Canadian
      Discharge Abstract Database, for April 2003-March 2010. Stratified, weekly
      admissions were modeled as a function of viral activity, seasonality, and trend
      using Poisson regression models. RESULTS: An estimated 1 out of every 6.4
      admissions attributable to seasonal influenza (2003-April 2009) were coded to J10
      (influenza virus identified). During the 2009 pandemic (May-March 2010), the
      influenza virus was identified in 1 of 1.6 admissions (95% CI, 1.5-1.7)
      attributed to the pandemic strain. Compared with previous H1N1 seasons (2007/08,
      2008/09), the influenza-attributed hospitalization rate for persons <65 years was
      approximately six times higher during the 2009 H1N1 pandemic, whereas for persons
      75 years or older, the pandemic rate was approximately fivefold lower.
      CONCLUSIONS: Case ascertainment was much improved during the pandemic period,
      with under ascertainment of admissions due to H1N1/2009 limited primarily to
      patients with a diagnosis of pneumonia.

PMID- 23122190
TI  - Impact of size and sorption on degradation of trichloroethylene and
      polychlorinated biphenyls by nano-scale zerovalent iron.
AB  - Nano-scale zerovalent iron (nZVI) has been studied in recent years for
      environmental remediation applications such as the degradation of chlorinated
      organic contaminants. To overcome limitations related to the transport of nZVI,
      it is becoming common to add a polymer stabilizer to limit aggregation and
      enhance the particle reactivity. Another method investigated to enhance particle
      reactivity has been to limit particle size through novel synthesis techniques.
      However, the relative impacts of particle size and interactions of the chemicals
      with the coatings are not yet well understood. The purpose of this study was to
      investigate the mechanisms of particle size and polymer coating or
      polyelectrolyte multilayer (PEM) synthesis conditions on degradation of two
      common chlorinated contaminants: trichloroethylene (TCE) and polychlorinated
      biphenyls (PCBs). This was accomplished using two different synthesis techniques,
      a layer-by-layer approach at different pH values or iron reduction in the
      presence of varying concentrations of poly(acrylic acid). nZVI produced by both
      techniques yielded higher degradation rates than a traditional approach. The
      mechanistic investigation indicated that hydrophobicity and sorption to the
      multilayer impacts the availability of the hydrophobic compound to the nZVI and
      that particle size also had a large role with smaller particles having stronger
      dechlorination rates.

PMID- 23122191
TI  - Arsenate reduction and methylation in the cells of Trichoderma asperellum SM
      12F1, Penicillium janthinellum SM-12F4, and Fusarium oxysporum CZ-8F1
      investigated with X-ray absorption near edge structure.
AB  - Synchrotron radiation-based X-ray absorption near edge structure (XANES) was
      introduced to directly analysis chemical species of arsenic (As) in the cells of
      Trichoderma asperellum SM-12F1, Penicillium janthinellum SM-12F4, and Fusarium
      oxysporum CZ-8F1 capable of As accumulation and volatilisation. After exposure to
      As(V) of 500 mg L(-1) for 15 days, a total of 60.5% and 65.3% of the accumulated
      As in the cells of T. asperellum SM-12F1 and P. janthinellum SM-12F4,
      respectively, was As(III), followed by 31.3% and 32.4% DMA (dimethylarsinic
      acid), 8.3% and 2.3% MMA (monomethylarsonic acid), respectively. However, for F.
      oxysporum CZ-8F1, 54.5% of the accumulated As was As(III), followed by 37.8% MMA
      and 7.7% As(V). The reduction and methylation of As(V) formed As(III), MMA, and
      DMA as the primacy products, and the reduction of As(V) might be more easily
      processed than the methylation. These results will help to understanding the
      mechanisms of As detoxification and its future application in bioremediation.

PMID- 23122192
TI  - Recycled water sources influence the bioavailability of copper to earthworms.
AB  - Re-use of wastewaters can overcome shortfalls in irrigation demand and mitigate
      environmental pollution. However, in an untreated or partially treated state,
      these water sources can introduce inorganic contaminants, including heavy metals,
      to soils that are irrigated. In this study, earthworms (Eisenia fetida) have been
      used to determine copper (Cu) bioavailability in two contrasting soils irrigated
      with farm dairy, piggery and winery effluents. Soils spiked with varying levels
      of Cu (0-1,000 mg/kg) were subsequently irrigated with recycled waters and Milli
      Q (MQ) water and Cu bioavailability to earthworms determined by mortality and
      avoidance tests. Earthworms clearly avoided high Cu soils and the effect was more
      pronounced in the absence than presence of recycled water irrigation. At the
      highest Cu concentration (1,000 mg/kg), worm mortality was 100% when irrigated
      with MQ-water; however, when irrigated with recycled waters, mortality decreased
      by 30%. Accumulation of Cu in earthworms was significantly less in the presence
      of recycled water and was dependent on CaCl2-extractable free Cu(2+)
      concentration in the soil. Here, it is evident that organic carbon in recycled
      waters was effective in decreasing the toxic effects of Cu on earthworms,
      indicating that the metal-organic complexes decreased Cu bioavailability to
      earthworms.

PMID- 23122193
TI  - Positioning ENA for the future.

PMID- 23122194
TI  - Is your emergency department "kid ready?".

PMID- 23122195
TI  - "Back to the future" for emergency care.

PMID- 23122196
TI  - Accurate patient identification in the emergency department.

PMID- 23122197
TI  - Twelve-hour shifts.

PMID- 23122198
TI  - Promotion of just culture in the emergency department.

PMID- 23122199
TI  - Response to: "Development of consensus statement on definitions for consistent
      emergency department metrics".

PMID- 23122200
TI  - A 33-year-old soldier with blunt cardiac arrest.

PMID- 23122201
TI  - Ten things we might not want to do anymore: how research changes nursing
      practice.

PMID- 23122202
TI  - Applications of life cycle assessment and cost analysis in health care waste
      management.
AB  - The establishment of rules to manage Health Care Waste (HCW) is a challenge for
      the public sector. Regulatory agencies must ensure the safety of waste management
      alternatives for two very different profiles of generators: (1) hospitals, which
      concentrate the production of HCW and (2) small establishments, such as clinics,
      pharmacies and other sources, that generate dispersed quantities of HCW and are
      scattered throughout the city. To assist in developing sector regulations for the
      small generators, we evaluated three management scenarios using decision-making
      tools. They consisted of a disinfection technique (microwave, autoclave and lime)
      followed by landfilling, where transportation was also included. The microwave,
      autoclave and lime techniques were tested at the laboratory to establish the
      operating parameters to ensure their efficiency in disinfection. Using a life
      cycle assessment (LCA) and cost analysis, the decision-making tools aimed to
      determine the technique with the best environmental performance. This consisted
      of evaluating the eco-efficiency of each scenario. Based on the life cycle
      assessment, microwaving had the lowest environmental impact (12.64 Pt) followed
      by autoclaving (48.46 Pt). The cost analyses indicated values of US$0.12 kg(-1)
      for the waste treated with microwaves, US$1.10 kg(-1) for the waste treated by
      the autoclave and US$1.53 kg(-1) for the waste treated with lime. The microwave
      disinfection presented the best eco-efficiency performance among those studied
      and provided a feasible alternative to subsidize the formulation of the policy
      for small generators of HCW.

PMID- 23122203
TI  - Effects of pH and microbial composition on odour in food waste composting.
AB  - A major problem for composting plants is odour emission. Slow decomposition
      during prolonged low-pH conditions is a frequent process problem in food waste
      composting. The aim was to investigate correlations between low pH, odour and
      microbial composition during food waste composting. Samples from laboratory
      composting experiments and two large scale composting plants were analysed for
      odour by olfactometry, as well as physico-chemical and microbial composition.
      There was large variation in odour, and samples clustered in two groups, one with
      low odour and high pH (above 6.5), the other with high odour and low pH (below
      6.0). The low-odour samples were significantly drier, had lower nitrate and TVOC
      concentrations and no detectable organic acids. Samples of both groups were
      dominated by Bacillales or Actinobacteria, organisms which are often indicative
      of well-functioning composting processes, but the high-odour group DNA sequences
      were similar to those of anaerobic or facultatively anaerobic species, not to
      typical thermophilic composting species. High-odour samples also contained
      Lactobacteria and Clostridia, known to produce odorous substances. A proposed
      odour reduction strategy is to rapidly overcome the low pH phase, through high
      initial aeration rates and the use of additives such as recycled compost.

PMID- 23122204
TI  - Assessment of medical waste management at a primary health-care center in Sao
      Paulo, Brazil.
AB  - According to the Brazilian law, implementation of a Medical Waste Management Plan
      (MWMP) in health-care units is mandatory, but as far as we know evaluation of
      such implementation has not taken place yet. The purpose of the present study is
      to evaluate the improvements deriving from the implementation of a MWMP in a
      Primary Health-care Center (PHC) located in the city of Sao Paulo, Brazil. The
      method proposed for evaluation compares the first situation prevailing at this
      PHC with the situation 1 year after implementation of the MWMP, thus allowing
      verification of the evolution of the PHC performance. For prior and post
      diagnosis, the method was based on: (1) application of a tool (check list) which
      considered all legal requirements in force; (2) quantification of solid waste
      subdivided into three categories: infectious waste and sharp devices, recyclable
      materials and non-recyclable waste; and (3) identification of non-conformity
      practices. Lack of knowledge on the pertinent legislation by health workers has
      contributed to non-conformity instances. The legal requirements in force in
      Brazil today gave origin to a tool (check list) which was utilized in the
      management of medical waste at the health-care unit studied. This tool resulted
      into an adequate and simple instrument, required a low investment, allowed
      collecting data to feed indicators and also conquered the participation of the
      unit whole staff. Several non-conformities identified in the first diagnosis
      could be corrected by the instrument utilized. Total waste generation increased
      9.8%, but it was possible to reduce the volume of non-recyclable materials (11%)
      and increase the volume of recyclable materials (4%). It was also possible to
      segregate organic waste (7%), which was forwarded for production of compost. The
      rate of infectious waste generation in critical areas decreased from 0.021 to
      0.018 kg/procedure. Many improvements have been observed, and now the PHC
      complies with most of legal requirements, offers periodic training and better
      biosafety conditions to workers, has reduced the volume of waste sent to sanitary
      landfills, and has introduced indicators for monitoring its own performance. This
      evaluation method might subsidize the creation and evaluation of medical waste
      management plans in similar heath institutions.

PMID- 23122205
TI  - Impact of Construction Waste Disposal Charging Scheme on work practices at
      construction sites in Hong Kong.
AB  - Waste management in the building industry in Hong Kong has become an important
      environmental issue. Particularly, an increasing amount of construction and
      demolition (C&D) waste is being disposed at landfill sites. In order to reduce
      waste generation and encourage reuse and recycling, the Hong Kong Government has
      implemented the Construction Waste Disposal Charging Scheme (CWDCS) to levy
      charges on C&D waste disposal to landfills. In order to provide information on
      the changes in reducing waste generation practice among construction participants
      in various work trades, a study was conducted after 3 years of implementation of
      the CWDCS via a structured questionnaire survey in the building industry in Hong
      Kong. The study result has revealed changes with work flows of the major trades
      as well as differentiating the levels of waste reduced. Three building projects
      in the public and private sectors were selected as case studies to demonstrate
      the changes in work flows and the reduction of waste achieved. The research
      findings reveal that a significant reduction of construction waste was achieved
      at the first 3 years (2006-2008) of CWDCS implementation. However, the reduction
      cannot be sustained. The major trades have been influenced to a certain extent by
      the implementation of the CWDCS. Slight improvement in waste management practices
      was observed, but reduction of construction waste in the wet-finishing and dry
      finishing trades has undergone little improvement. Implementation of the CWDCS
      has not yet motivated subcontractors to change their methods of construction so
      as to reduce C&D waste.

PMID- 23122206
TI  - Tank-connected food waste disposer systems--current status and potential
      improvements.
AB  - An unconventional system for separate collection of food waste was investigated
      through evaluation of three full-scale systems in the city of Malmo, Sweden.
      Ground food waste is led to a separate settling tank where food waste sludge is
      collected regularly with a tank-vehicle. These tank-connected systems can be seen
      as a promising method for separate collection of food waste from both households
      and restaurants. Ground food waste collected from these systems is rich in fat
      and has a high methane potential when compared to food waste collected in
      conventional bag systems. The content of heavy metals is low. The concentrations
      of N-tot and P-tot in sludge collected from sedimentation tanks were on average
      46.2 and 3.9 g/kg TS, equalling an estimated 0.48 and 0.05 kg N-tot and P-tot
      respectively per year and household connected to the food waste disposer system.
      Detergents in low concentrations can result in increased degradation rates and
      biogas production, while higher concentrations can result in temporary inhibition
      of methane production. Concentrations of COD and fat in effluent from full-scale
      tanks reached an average of 1068 mg/l and 149 mg/l respectively over the five
      month long evaluation period. Hydrolysis of the ground material is initiated
      between sludge collection occasions (30 days). Older food waste sludge increases
      the degradation rate and the risks of fugitive emissions of methane from tanks
      between collection occasions. Increased particle size decreases hydrolysis rate
      and could thus decrease losses of carbon and nutrients in the sewerage system,
      but further studies in full-scale systems are needed to confirm this.

PMID- 23122207
TI  - Double-Ovsynch in high-producing dairy cows: effects on progesterone
      concentrations and ovulation to GnRH treatments.
AB  - Previous studies reported increased fertility using Ovsynch for
      presynchronization before Ovsynch (Double-Ovsynch), as compared with
      presynchronization with two prostaglandin F(2alpha) (PGF(2alpha)) treatments
      before Ovsynch (Presynch-Ovsynch). This study compared ovarian follicular
      dynamics and hormone concentrations during Double-Ovsynch versus Presynch
      Ovsynch. Lactating Holstein cows (N = 193) were assigned to one of two treatment
      groups: (1) Presynch (N = 93), two injections of PGF(2alpha) 14 days apart,
      followed by the Ovsynch-timed AI protocol 12 days later; and (2) Double-Ovsynch
      (N = 100), one injection of GnRH, PGF(2alpha) 7 days later, and GnRH 3 days
      later, followed by the Ovsynch-timed AI protocol 7 days later. All cows received
      the same Ovsynch-timed AI protocol: GnRH (G1) at 68 +/- 3 days in milk (mean +/-
      SEM), PGF(2alpha) 7 days later, and GnRH (G2) 56 hours after PGF(2alpha).
      Ultrasonographic evaluations of the ovaries and blood sampling were performed at
      G1, PGF(2alpha), G2, and 6 days after the G2 injection of the Ovsynch-timed AI
      protocol. Double-Ovsynch decreased the percentage of cows with low circulating
      progesterone (P4) concentrations (<0.50 ng/mL) at G1 (12.0% vs. 30.1%; P = 0.003)
      and increased the percentage of cows with medium P4 concentrations (0.50 > P4 <=
      3.0 ng/mL) at G1 (80.0% vs. 57.0%; P < 0.01), and with CL at G1 (94.0% vs. 67.8%;
      P < 0.01). Double-Ovsynch also increased the percentage of cows with high P4
      (>3.0 ng/mL) at PGF(2alpha) (88.0% vs. 76.3%; P = 0.04) and tended to increase
      average circulating P4 at PGF(2alpha) (3.52 +/- 0.17 ng/mL vs. 3.09 +/- 0.21
      ng/mL; P = 0.11). Double-Ovsynch also tended to increase percentage of cows
      ovulating to G1 (80.0% vs. 69.9%; P = 0.11) and G2 (98.0% vs. 93.5%; P = 0.08).
      Thus, presynchronization of cows with Double-Ovsynch induced ovulation in
      noncycling cows and appeared to increase most aspects of synchronization during
      the Ovsynch protocol.

PMID- 23122208
TI  - Comparison of a leukocyte esterase test with endometrial cytology for diagnosis
      of subclinical endometritis in postpartum dairy cows.
AB  - The objective was to compare a leukocyte esterase (LE) test with endometrial
      cytology (EC) for diagnosis of subclinical endometritis in dairy cows. The
      relationship between subsequent fertility and the uterine (Ut) and cervical (Cx)
      leukocyte esterase activity was determined by the odds of pregnancy by 90 days in
      milk (DIM). Holstein cows (N = 218) without clinical endometritis and between 21
      and 47 DIM from five commercial dairy herds were sampled for uterine and cervical
      leukocyte esterase activity and EC by cytobrush. To test the effect of time, cows
      were grouped into early (21-31 DIM) and late (32-47 DIM) animals. There was a
      slight agreement between UtLE and CxLE (weighted kappa = 0.37). The percentage of
      neutrophils was correlated with esterase score either from the uterus (UtLE; P =
      0.0001) or cervix (CxLE; P = 0.002). The percentage of neutrophils on EC (P <
      0.001), the UtLE score (P < 0.0001), and the CxLE (P = 0.0009) diminished as DIM
      increased. Neither CxLE nor UtLE were statistically associated with pregnancy at
      90 DIM. However, between 32 and 47 DIM, the percentage of neutrophils on EC and
      odds of pregnancy at 90 DIM were associated (P = 0.04). For the same interval,
      based on receiver/response operating characteristics analysis, the optimal cutoff
      was >6.7% neutrophils to classify cows with subclinical endometritis. In
      conclusion, uterine LE activity was correlated with percentage of neutrophils as
      determined by EC, but not with odds of pregnancy. Subclinical endometritis
      (>6.70% neutrophils) diagnosed by EC between 32 and 47 DIM was associated with
      reduced odds of pregnancy.

PMID- 23122209
TI  - Evolution and diversity of periplasmic proteins involved in copper homeostasis in
      gamma proteobacteria.
AB  - BACKGROUND: Different systems contributing to copper homeostasis in bacteria have
      been described in recent years involving periplasmic and transport proteins that
      provide resistance via metal efflux to the extracellular media (CopA/Cue, Cus,
      Cut, and Pco). The participation of these proteins in the assembly of membrane,
      periplasmic and secreted cuproproteins has also been postulated. The integration
      and interrelation of these systems and their apparent redundancies are less clear
      since they have been studied in alternative systems. Based on the idea that
      cellular copper is not free but rather it is transferred via protein-protein
      interactions, we hypothesized that systems would coevolve and be constituted by
      set numbers of essential components. RESULTS: By the use of a phylogenomic
      approach we identified the distribution of 14 proteins previously characterized
      as members of homeostasis systems in the genomes of 268 gamma proteobacteria.
      Only 3% of the genomes presented the complete systems and 5% of them, all
      intracellular parasites, lacked the 14 genes. Surprisingly, copper homeostatic
      pathways did not behave as evolutionary units with particular species assembling
      different combinations of basic functions. The most frequent functions, and
      probably because of its distribution the most vital, were copper extrusion from
      the cytoplasm to the periplasm performed by CopA and copper export from the
      cytoplasm to the extracellular space performed by CusC, which along with the
      remaining 12 proteins, assemble in nine different functional repertoires.
      CONCLUSIONS: These observations suggest complex evolutionary dynamics and still
      unexplored interactions to achieve copper homeostasis, challenging some of the
      molecular transport mechanism proposed for these systems.

PMID- 23122210
TI  - Feasibility and safety study of day-case TranstarTM procedure.
AB  - BACKGROUND: Short hospitalization surgery is cost effective and convenient for
      both patients and healthcare system. Stapled transanal rectal resection (STARR)
      conducted with the new curved device, Contour Transtar, has proved an effective
      and safe procedure for treatment of obstructed defecation syndrome. The aim of
      this study was to determine the safety and feasibility of STARR, performed as a
      day-case procedure. MATERIAL AND METHODS: Retrospective review was performed of
      all STARR performed as day-case surgery between September 2009 and February 2011.
      The entire study (intervention, data collection and data analysis) was conducted
      at the One-day Surgery Unit of the St. Andrea Hospital, Rome, Italy. All patients
      with surgical indication to STARR for the presence of an obstructed defecation
      syndrome were included in the study. We excluded from day-case protocol, patients
      over 65 years old, with an ASA score of III-IV or with a BMI over 35. The
      surgical technique reflects the original technique proposed by Antonio Longo with
      the exception of the longitudinal prolapse opening, which was created with the
      use of an electric scalpel between two Kocher clamps and not by an application of
      Transtar stapler. To evaluate the feasibility and safety of performing this
      procedure with short hospitalization, we investigated the presence and the time
      of presentation of post-operative complications. RESULTS: Eighty-nine patients
      underwent STARR as a day-case regimen, and none presented major complications or
      required an extension of hospital stay or readmission. CONCLUSIONS: STARR
      performed with Contour Transtar, in selected patients, is safe and feasible in
      day-case regimen if performed by expert surgeons and in a structure that allows
      the physician to keep the patient hospitalized or to re-admit and promptly treat
      those patients who present major surgical complication.

PMID- 23122211
TI  - Acute and second-meal effects of peanuts on glycaemic response and appetite in
      obese women with high type 2 diabetes risk: a randomised cross-over clinical
      trial.
AB  - Nut consumption is associated with a reduced risk of type 2 diabetes mellitus
      (T2DM). The aim of the present study was to assess the effects of adding peanuts
      (whole or peanut butter) on first (0-240 min)- and second (240-490 min)-meal
      glucose metabolism and selected gut satiety hormone responses, appetite ratings
      and food intake in obese women with high T2DM risk. A group of fifteen women
      participated in a randomised cross-over clinical trial in which 42.5 g of whole
      peanuts without skins (WP), peanut butter (PB) or no peanuts (control) were added
      to a 75 g available carbohydrate-matched breakfast meal. Postprandial
      concentrations (0-490 min) of glucose, insulin, NEFA, glucagon-like peptide-1
      (GLP-1), peptide YY (PYY), cholecystokinin (CCK), appetitive sensations and food
      intake were assessed after breakfast treatments and a standard lunch.
      Postprandial NEFA incremental AUC (IAUC) (0-240 min) and glucose IAUC (240-490
      min) responses were lower for the PB breakfast compared with the control
      breakfast. Insulin concentrations were higher at 120 and 370 min after the PB
      consumption than after the control consumption. Desire-to-eat ratings were lower,
      while PYY, GLP-1 and CCK concentrations were higher after the PB intake compared
      with the control intake. WP led to similar but non-significant effects. The
      addition of PB to breakfast moderated postprandial glucose and NEFA
      concentrations, enhanced gut satiety hormone secretion and reduced the desire to
      eat. The greater bioaccessibility of the lipid component in PB is probably
      responsible for the observed incremental post-ingestive responses between the nut
      forms. Inclusion of PB, and probably WP, to breakfast may help to moderate
      glucose concentrations and appetite in obese women.

PMID- 23122212
TI  - Specialized family planning clinics in the United States: why women choose them
      and their role in meeting women's health care needs.
AB  - BACKGROUND: Publicly funded family planning clinics provide contraceptive care to
      millions of poor and low-income women every year. To inform the design of
      services that will best meet the contraceptive and reproductive health needs of
      women, we conducted a targeted survey of family planning clinic clients, asking
      women about services received in the past year and about their reasons for
      visiting a specialized family planning clinic. METHODS: We surveyed 2,094 women
      receiving services from 22 family planning clinics in 13 states; all sites
      included in the survey were clinics that specialize in contraceptive and
      reproductive health services and were located in communities with comprehensive
      primary care providers. RESULTS: Six in 10 (59%) respondents had made a health
      care visit to another provider in the past year, but chose the family planning
      clinic for contraceptive care. Four in 10 (41%) respondents relied on the family
      planning clinic as their only recent source for health care. The four most common
      reasons for choosing a specialized family planning clinic, reported by at least
      80% of respondents, were respectful staff, confidential care, free or low-cost
      services, and staff who are knowledgeable about women's health. CONCLUSIONS:
      Specialized family planning clinics play an important role as part of the health
      care safety net in the United States. Collaborations between such clinics and
      comprehensive primary care providers, such as federally qualified health centers,
      may be one model for ensuring women on-going access to the full range of care
      they need.

PMID- 23122213
TI  - "What my doctor didn't tell me": examining health care provider advice to
      overweight and obese pregnant women on gestational weight gain and physical
      activity.
AB  - BACKGROUND: Appropriate gestational weight gain (GWG) is vital, as excessive GWG
      is strongly associated with postpartum weight retention and long-term obesity.
      How health care providers counsel overweight and obese pregnant women on
      appropriate GWG and physical activity remains largely unexplored. METHODS: We
      conducted semistructured interviews with overweight and obese women after the
      birth of their first child to ascertain their experiences with GWG. A grounded
      theory approach was used to identify themes on provider advice received about GWG
      and physical activity during pregnancy. RESULTS: Twenty-four women were included
      in the analysis. Three themes emerged in discussions regarding provider advice on
      GWG: 1) Women were advised to gain too much weight or given no recommendation for
      GWG at all, 2) providers were perceived as being unconcerned about excessive GWG,
      and 3) women desire and value GWG advice from their providers. On the topic of
      provider advice on exercise in pregnancy, three themes were identified: 1) Women
      received limited or no advice on appropriate physical activity during pregnancy,
      2) women were advised to be cautious and limit exercise during pregnancy, and 3)
      women perceived that provider knowledge on appropriate exercise intensity and
      frequency in pregnancy was limited. CONCLUSIONS: This study suggests that
      provider advice on GWG and exercise is insufficient and often inappropriate, and
      thus unlikely to positively influence how overweight and obese women shape goals
      and expectations in regard to GWG and exercise behaviors. Interventions to help
      pregnant women attain healthy GWG and adequate physical activity are needed.

PMID- 23122214
TI  - Knowledge, attitudes, and beliefs regarding HPV vaccination: ethnic and cultural
      differences between African-American and Haitian immigrant women.
AB  - BACKGROUND: Black women have higher rates of cervical cancer and lower rates of
      HPV vaccination than White women in the United States, and Haitians may be an
      especially vulnerable subgroup of Black women. To reduce these disparities,
      understanding differences among subgroups of Black women is crucial. METHODS: The
      objective of our study was to assess similarities and differences in the
      knowledge, attitudes, beliefs, and practices toward HPV vaccination and actual
      vaccination rates among African-American and Haitian immigrant women and their
      daughters. We used validated surveys of HPV knowledge, trust in physicians,
      acculturation, and constructs of the health belief model: Perceived
      susceptibility, severity, and barriers. We probed women's thought processes about
      vaccination using open-ended questions. We then reviewed medical records to
      determine vaccination rates. RESULTS: Nineteen African Americans and 51 Haitians
      participated. Although 75% of Haitians and 63% of African Americans intended to
      vaccinate their daughters, only 47% of African-American and 31% of Haitian
      daughters were vaccinated. African Americans were more knowledgeable than
      Haitians and had more prior experience with HPV disease. Most African Americans
      felt that vaccination fell within the parental role, whereas many Haitians felt
      uncomfortable vaccinating against sexually transmitted infections because they
      felt children should not be having sex. Both ethnic groups wanted more
      information about HPV vaccines. CONCLUSION: Cultural differences between African
      American and Haitian immigrant mothers revealed distinct barriers for vaccine
      acceptance. Improving HPV vaccine rates in Black women may require culturally
      competent and sensitive approaches that address ethnic-specific barriers.

PMID- 23122215
TI  - What should we be selecting for? A systematic approach for determining which
      personal characteristics to assess for during admissions.
AB  - BACKGROUND: Admission committees are responsible for creating fair, defensible,
      reliable, and valid processes that assess those attributes considered important
      for professional success. There is evidence for the continuing use of academic
      ability as a selection criterion for health professional schools; however, there
      is little evidence for the reliability and validity of measures currently in
      place to assess personal characteristics. The Ontario Veterinary College (OVC)
      initiated a review of its admissions criteria in order to implement an evidence
      based method to determine which characteristics veterinary stakeholders consider
      important to assess for admission. METHODS: Eleven characteristics were
      identified by the OVC Admissions Committee and a survey was sent to all licensed
      veterinarians in Ontario (n=4,068), OVC students (n=450), and OVC faculty,
      interns and residents (n=192). A paired comparison method was used to identify
      the relative rank order of the characteristics, and multivariate analysis of
      variance with post hoc analyses was used to determine between group differences
      in the returned survey data. RESULTS: Surveys were returned from 1,312
      participants (27.86% response rate; female 59.70%). The relative rank of the
      characteristics was reasonably consistent among participant groups, with ethical
      behaviour, sound judgment, communication, and critical and creative thinking
      being ranked as the top four. However, the importance of certain characteristics
      like communication and empathy were perceived differently by groups. For
      instance, females scored communication (F(1, 1289) = 20.24, p < .001, d = .26)
      and empathy (F(1, 1289) = 55.41, p < .001, d = 0.42) significantly higher than
      males, while males scored knowledge of profession (F(1, 1289) = 12.81, p < .001,
      d = 0.20), leadership (F(1, 1289) = 10.28, p = .001, d = 0.18), and sound
      judgment (F(1, 1289) = 13.56, p < .001, d = 0.21) significantly higher than
      females. CONCLUSIONS: The data from the paired comparison method provide
      convergent evidence for the characteristics participant groups identify as most
      important in determining who should be admitted to a veterinary program. The
      between group analyses provides important information regarding characteristics
      most important to various subgroups; this has implications for what
      characteristics are selected for at admission as well as on who is selecting for
      them.

PMID- 23122216
TI  - Yeast response to LA virus indicates coadapted global gene expression during
      mycoviral infection.
AB  - Viruses that infect fungi have a ubiquitous distribution and play an important
      role in structuring fungal communities. Most of these viruses have an unusual
      life history in that they are propagated exclusively via asexual reproduction or
      fission of fungal cells. This asexual mode of transmission intimately ties viral
      reproductive success to that of its fungal host and should select for viruses
      that have minimal deleterious impact on the fitness of their hosts. Accordingly,
      viral infections of fungi frequently do not measurably impact fungal growth, and
      in some instances, increase the fitness of the fungal host. Here we determine the
      impact of the loss of coinfection by LA virus and the virus-like particle M1 upon
      global gene expression of the fungal host Saccharomyces cerevisiae and provide
      evidence supporting the idea that coevolution has selected for viral infection
      minimally impacting host gene expression.

PMID- 23122218
TI  - The Affordable Medicines Facility--malaria: killing it slowly.

PMID- 23122219
TI  - Artemisinin-resistant malaria in the Asia-Pacific region.

PMID- 23122217
TI  - Effect of the Affordable Medicines Facility--malaria (AMFm) on the availability,
      price, and market share of quality-assured artemisinin-based combination
      therapies in seven countries: a before-and-after analysis of outlet survey data.
AB  - BACKGROUND: Malaria is one of the greatest causes of mortality worldwide. Use of
      the most effective treatments for malaria remains inadequate for those in need,
      and there is concern over the emergence of resistance to these treatments. In
      2010, the Global Fund launched the Affordable Medicines Facility--malaria (AMFm),
      a series of national-scale pilot programmes designed to increase the access and
      use of quality-assured artemisinin based combination therapies (QAACTs) and
      reduce that of artemisinin monotherapies for treatment of malaria. AMFm involves
      manufacturer price negotiations, subsidies on the manufacturer price of each
      treatment purchased, and supporting interventions such as communications
      campaigns. We present findings on the effect of AMFm on QAACT price,
      availability, and market share, 6-15 months after the delivery of subsidised ACTs
      in Ghana, Kenya, Madagascar, Niger, Nigeria, Uganda, and Tanzania (including
      Zanzibar). METHODS: We did nationally representative baseline and endpoint
      surveys of public and private sector outlets that stock antimalarial treatments.
      QAACTs were identified on the basis of the Global Fund's quality assurance
      policy. Changes in availability, price, and market share were assessed against
      specified success benchmarks for 1 year of AMFm implementation. Key informant
      interviews and document reviews recorded contextual factors and the
      implementation process. FINDINGS: In all pilots except Niger and Madagascar,
      there were large increases in QAACT availability (25.8-51.9 percentage points),
      and market share (15.9-40.3 percentage points), driven mainly by changes in the
      private for-profit sector. Large falls in median price for QAACTs per adult
      equivalent dose were seen in the private for-profit sector in six pilots, ranging
      from US$1.28 to $4.82. The market share of oral artemisinin monotherapies
      decreased in Nigeria and Zanzibar, the two pilots where it was more than 5% at
      baseline. INTERPRETATION: Subsidies combined with supporting interventions can be
      effective in rapidly improving availability, price, and market share of QAACTs,
      particularly in the private for-profit sector. Decisions about the future of AMFm
      should also consider the effect on use in vulnerable populations, access to
      malaria diagnostics, and cost-effectiveness. FUNDING: The Global Fund to Fight
      AIDS, Tuberculosis and Malaria, and the Bill & Melinda Gates Foundation.

PMID- 23122220
TI  - Ambulatory measurement of the knee adduction moment in patients with
      osteoarthritis of the knee.
AB  - High knee joint-loading increases the risk and progression of knee osteoarthritis
      (OA). Mechanical loading on the knee is reflected in the external knee adduction
      moment (KAdM) that can be measured during gait with laboratory-based measurement
      systems. However, clinical application of these systems is limited. Ambulatory
      movement analysis systems, including instrumented force shoes (IFS) and an
      inertial and magnetic measurement system (IMMS), could potentially be used to
      determine the KAdM in a laboratory-free setting. Promising results have been
      reported concerning the use of the IFS in KAdM measurements; however its
      application in combination with IMMS has not been studied. The objective of this
      study was to compare the KAdM measured with an ambulatory movement analysis
      system with a laboratory-based system in patients with knee OA. Gait analyses of
      14 knee OA patients were performed in a gait laboratory. The KAdM was
      concurrently determined with two the systems: (i) Ambulatory: IFS and IMMS in
      combination with a linked-segment model (to obtain joint positions); (ii)
      Laboratory: force plate and optoelectronic marker system. Mean differences in
      KAdM between the ambulatory and laboratory system were not significant (maximal
      difference 0.20%BW*H in late stance, i.e. 5.6% of KAdM range, P>0.05) and below
      clinical relevant and hypothesized differences, showing no systematic differences
      at group level. Absolute differences were on average 24% of KAdM range, i.e.
      0.83%BW*H, particularly in early and late stance. To achieve greater accuracy for
      clinical use, estimation of joint position via a more advanced calibrated linked
      segment model should be investigated.

PMID- 23122222
TI  - Tekscan pressure sensor output changes in the presence of liquid exposure.
AB  - The purpose of the study was to evaluate the load output of a pressure sensor in
      the presence of liquid saturation in a controlled environment. We hypothesized
      that a calibrated pressure sensor would provide diminishing load outputs over
      time in controlled environments of both humidified air and while submerged in
      saline and the sensors would reach a steady state output once saturated. A
      consistent compressive load was repeatedly applied to pressure sensors over time
      (Model 4000, Tekscan, Inc., South Boston, MA) with a tensile testing machine
      (Instron ElectroPuls E10000, Norwood, MA). All sensors were initially calibrated
      in a dry environment and were tested in three groups: humid air, submerged in
      0.9% saline solution, and dry. Linear regression of load output over time for the
      pressure sensors exposed to humidity and submerged showed a 4.6% and 4.7% decline
      in load output each hour for the initial 6h, respectively (beta=-0.046, 95% CI: [
      0.053 to -0.039]; p<0.001) (beta=-0.047, 95% CI: [-0.053 to -0.042; p<0.001).
      Tests after 72 h of exposure had linear regression decline in load output over
      time of 0.40% and 0.47% per hour for humidified and submerged sensors,
      respectively (beta=-0.004, 95% CI: [-0.006 to -0.003]; p<0.001) (beta=-0.047, 95%
      CI: [-0.053 to -0.042]; p<0.001). Because outcomes in biomedical research can
      affect clinical practices and treatments, the diminishing load output of the
      sensor in the presence of liquids should be accounted for. We recommend soaking
      sensors for more than 48 h prior to testing in a moist environment.

PMID- 23122221
TI  - Dystrophic tendon functionality is recovered by muscle-specific expression of
      insulin-like growth factor in mdx mice.
AB  - Duchenne muscular dystrophy (DMD) is a severe genetic disorder of skeletal
      muscle, characterized by a steady muscle weakness. By using the animal model for
      DMD, the mdx mice, we have previously demonstrated that biomechanical properties
      of tendinous tissue are also significantly affected in this muscle pathology.
      Muscle specific over-expression of insulin like growth factor-1 (mIgf-1) is known
      to induce a partial recovery in muscle functionality, in particular increasing
      the muscle absolute force, but not the specific force. To test whether Igf-1
      muscle specific over-expression helps the recovery also in tendinous tissue,
      mechanical and cellular evaluation of mdx and mdx:MLC/mIgf-1 mice tendons has
      been performed. Mechanical properties were investigated by measuring the
      viscoelastic response of the tissue, while cell viability was evaluated by
      molecular assays. An absolute recovery in the mechanical properties of EDL and TA
      tendons was observed through the measurement of tissue viscoelasticity for
      several different frequencies of interest. Moreover, when compared with tendons
      from dystrophic mdx animals, mdx:MLC/mIgf-1 specimens showed an almost complete
      recovery in the number of viable cells for both extensor digitorum longus (EDL)
      and tibialis anterior (TA) tendons. Of note, the partial recovery in muscle
      functionality and the full recovery in tendons response, suggests that mIgf-1
      muscle specific over-expression exerts its effect on tendons either indirectly,
      improving the tendon viability and its functional properties as a consequence of
      the reduction of the hostile muscle dystrophic environment, or acting directly on
      the tendon tissue, as a paracrine trophic factor.

PMID- 23122223
TI  - Pendulum mass affects the measurement of articular friction coefficient.
AB  - Friction measurements of articular cartilage are important to determine the
      relative tribologic contributions made by synovial fluid or cartilage, and to
      assess the efficacy of therapies for preventing the development of post-traumatic
      osteoarthritis. Stanton's equation is the most frequently used formula for
      estimating the whole joint friction coefficient (MU) of an articular pendulum,
      and assumes pendulum energy loss through a mass-independent mechanism. This study
      examines if articular pendulum energy loss is indeed mass independent, and
      compares Stanton's model to an alternative model, which incorporates viscous
      damping, for calculating MU. Ten loads (25-100% body weight) were applied in a
      random order to an articular pendulum using the knees of adult male Hartley
      guinea pigs (n=4) as the fulcrum. Motion of the decaying pendulum was recorded
      and MU was estimated using two models: Stanton's equation, and an exponential
      decay function incorporating a viscous damping coefficient. MU estimates
      decreased as mass increased for both models. Exponential decay model fit error
      values were 82% less than the Stanton model. These results indicate that MU
      decreases with increasing mass, and that an exponential decay model provides a
      better fit for articular pendulum data at all mass values. In conclusion, inter
      study comparisons of articular pendulum MU values should not be made without
      recognizing the loads used, as MU values are mass dependent.

PMID- 23122224
TI  - Acoustic radiation force impulse imaging of vulnerable plaques: a finite element
      method parametric analysis.
AB  - Plaque rupture is the most common cause of complications such as stroke and
      coronary heart failure. Recent histopathological evidence suggests that several
      plaque features, including a large lipid core and a thin fibrous cap, are
      associated with plaques most at risk for rupture. Acoustic Radiation Force
      Impulse (ARFI) imaging, a recently developed ultrasound-based elasticity imaging
      technique, shows promise for imaging these features noninvasively. Clinically,
      this could be used to distinguish vulnerable plaques, for which surgical
      intervention may be required, from those less prone to rupture. In this study, a
      parametric analysis using Finite Element Method (FEM) models was performed to
      simulate ARFI imaging of five different carotid artery plaques across a wide
      range of material properties. It was demonstrated that ARFI imaging could resolve
      the softer lipid pool from the surrounding, stiffer media and fibrous cap and was
      most dependent upon the stiffness of the lipid pool component. Stress
      concentrations due to an ARFI excitation were located in the media and fibrous
      cap components. In all cases, the maximum Von Mises stress was<1.2 kPa. In
      comparing these results with others investigating plaque rupture, it is concluded
      that while the mechanisms may be different, the Von Mises stresses imposed by
      ARFI imaging are orders of magnitude lower than the stresses associated with
      blood pressure.

PMID- 23122225
TI  - The effects of electrical stimulation exercise on muscles injected with botulinum
      toxin type-A (botox).
AB  - Botulinum toxin type A (BTX-A) is a frequently used treatment modality for a
      variety of neuromuscular disorders. It acts by preventing acetylcholine release
      at the motor nerve endings, inducing muscle paralysis. Although considered safe,
      studies suggest that BTX-A injections create adverse effects on target and non
      target muscles. We speculate that these adverse effects are reduced by direct
      electrical stimulation (ES) exercising of muscles. The aims were to determine the
      effects of ES exercise on strength, mass, and contractile material in BTX-A
      injected muscles, and to investigate if BTX-A injections affect non-target
      muscles. Seventeen New Zealand White (NZW) rabbits were divided into three
      groups: (1) Control group received saline injections; (2) BTX-A group received
      monthly BTX-A (3.5 U/kg) injections into the quadriceps for six months and (3)
      BTX-A+ES group received monthly BTX-A injections and ES exercise three times a
      week for six months. Outcome measures included knee extensor torque, muscle mass,
      and contractile material percentage area in injected and contralateral, non
      injected quadriceps. Glycogen depletion and direct muscle stimulation were used
      to assess possible muscle inhibition in non-injected quadriceps. ES exercise
      partially prevented muscle weakness, atrophy, and contractile material loss in
      injected muscles, and mostly prevented muscle degeneration in contralateral, non
      injected muscles. Non-injected muscles of BTX-A+ES group showed higher force with
      direct muscle compared to nerve stimulation, and retained glycogen following the
      depletion protocol, suggesting that BTX-A inhibited activation in non-target
      muscles. We conclude that ES exercise provides some protection from degeneration
      to target and non-target muscles during BTX-A treatments.

PMID- 23122226
TI  - Zebrafish Mnx proteins specify one motoneuron subtype and suppress acquisition of
      interneuron characteristics.
AB  - BACKGROUND: Precise matching between motoneuron subtypes and the muscles they
      innervate is a prerequisite for normal behavior. Motoneuron subtype identity is
      specified by the combination of transcription factors expressed by the cell
      during its differentiation. Here we investigate the roles of Mnx family
      transcription factors in specifying the subtypes of individually identified
      zebrafish primary motoneurons. RESULTS: Zebrafish has three Mnx family members.
      We show that each of them has a distinct and temporally dynamic expression
      pattern in each primary motoneuron subtype. We also show that two Mnx family
      members are expressed in identified VeLD interneurons derived from the same
      progenitor domain that generates primary motoneurons. Surprisingly, we found that
      Mnx proteins appear unnecessary for differentiation of VeLD interneurons or the
      CaP motoneuron subtype. Mnx proteins are, however, required for differentiation
      of the MiP motoneuron subtype. We previously showed that MiPs require two
      temporally-distinct phases of Islet1 expression for normal development. Here we
      show that in the absence of Mnx proteins, the later phase of Islet1 expression is
      initiated but not sustained, and MiPs become hybrids that co-express
      morphological and molecular features of motoneurons and V2a interneurons.
      Unexpectedly, these hybrid MiPs often extend CaP-like axons, and some MiPs appear
      to be entirely transformed to a CaP morphology. CONCLUSIONS: Our results suggest
      that Mnx proteins promote MiP subtype identity by suppressing both interneuron
      development and CaP axon pathfinding. This is, to our knowledge, the first report
      of transcription factors that act to distinguish CaP and MiP subtype identities.
      Our results also suggest that MiP motoneurons are more similar to V2 interneurons
      than are CaP motoneurons.

PMID- 23122227
TI  - Ablation of the Kell/Xk complex alters erythrocyte divalent cation homeostasis.
AB  - XK is a putative transporter of unknown function that is ubiquitously expressed
      and linked through disulfide bonds to Kell protein, an endothelin-3 (ET-3)
      converting enzyme. We generated three knockout (KO) mice that lacked either Xk,
      Kell or both proteins and characterized erythrocyte cation levels, transport and
      hematological parameters. Absence of Xk or Kell was accompanied by changes in
      erythrocyte K(+), Mg(2+), Na(+) and Ca(2+) transport that were associated with
      changes in mean cellular volume and corpuscular hemoglobin concentration mean.
      Baseline Ca(2+)-ATPase activity was undetected in erythrocytes from all three
      mouse types but was restored upon pre-incubation with ET-3. Consistent with these
      alterations in Ca(2+) handling, we observed increased Gardos channel activity in
      Kel and Xk KO mice. In addition Kel deletion was associated with increased Mg(2+)
      permeability while Xk deletion blocked Na/Mg exchanger activity. Our results
      provide evidence that cellular divalent cation regulation is functionally coupled
      to the Kell/XK system in erythrocytes and loss of this complex may contribute to
      acanthocytosis formation in McLeod syndrome.

PMID- 23122229
TI  - A novel luminescent biosensor for rapid monitoring of IP3 by split-luciferase
      complementary assay.
AB  - Inositol 1,4,5-trisphosphate (IP(3)) is a crucial second messenger that regulates
      complicated signaling processes in various physiological events. Alteration in
      its content has been observed in many diseases. Hence, development of a high
      throughput screening system to monitor temporal changes of IP(3) is essential for
      screening of new potential therapeutic compounds. Toward a simple, sensitive and
      rapid method for measuring IP(3), we describe the development and application of
      a novel biosensor based on luciferase fragment assisted complementation strategy,
      which converts the ligand-induced conformational changes to light. Designed
      sensor comprising the IP(3)-binding core domain of IP(3)-receptor fused between
      complementary non-functional fragments of firefly luciferase allows direct
      detection of IP(3) in presence of luciferin substrate both in cell lysate and in
      living cells. According to the result presented in this manuscript, the screening
      time was very fast and maximum response was obtained up to 11-fold higher than
      untreated cells. Moreover, the designed biosensor was able to monitor release of
      IP(3) upon induction by different inducers like Bradykinin and ATP. The current
      biosensor not only provides a specific IP(3) detector in vitro but also
      facilitates monitoring of the response of IP(3) in living organisms.

PMID- 23122228
TI  - Neutralizing and protective epitopes of the 2009 pandemic influenza H1N1
      hemagglutinin.
AB  - AIMS AND METHODS: To facilitate antigenic characterization of the influenza A
      2009 pandemic H1N1 [A(H1N1)pdm09] hemagglutinin (HA), we generated a panel of
      murine monoclonal antibodies (mAbs) using as the immunogen mammalian-derived
      virus-like particles containing the HA of the A/California/04/2009 virus. The
      antibodies were specific for the A/California/04/2009 HA, and individual mAbs
      suitable for use in several practical applications including ELISA,
      immunofluorescence, and Western blot analysis were identified. RESULTS AND
      CONCLUSIONS: As the panel of mAbs included antibodies with hemagglutination
      inhibition (HI) and virus neutralizing activities, this allowed identification
      and characterization of potentially important antigenic and neutralizing epitopes
      of the A/California/04/2009 HA and comparison of those epitopes with the HAs of
      other influenza viruses including seasonal H1N1 viruses as well as the A/South
      Carolina/1918 and A/New Jersey/1976 H1N1 viruses. Three mAbs with the highest HI
      and neutralizing titers were able to provide passive protection against virus
      challenge. Two other mAbs without HI or neutralizing activities were able to
      provide partial protection against challenge. HA epitopes recognized by the
      strongest neutralizing mAbs in the panel were identified by isolation and
      selection of virus escape mutants in the presence of individual mAbs. Cloned
      viruses resistant to HI and antibody neutralization were sequenced to identify
      mutations, and two unique mutations (D127E and G155E) were identified, both near
      the antigenic site Sa. Using human post-vaccination sera, however, there were no
      differences in HI titer between A/California/04/2009 and either escape mutant,
      suggesting that these single mutations were not sufficient to abrogate a
      protective antibody response to the vaccine.

PMID- 23122230
TI  - Visual detection of STAT5B gene expression in living cell using the hairpin DNA
      modified gold nanoparticle beacon.
AB  - Signal transducer and activator of transcription 5B (STAT5B) is an important
      protein in JAK-STAT signaling pathway that is responsible for the metastasis and
      proliferation of tumor cells. Determination of the STAT5B messenger Ribonucleic
      Acid (mRNA) relating to the STAT5B expression provides insight into the mechanism
      of tumor progression. In this study, we designed and used a special hairpin
      deoxyribonucleic acid (DNA) for human STAT5B mRNA to functionalize gold
      nanoparticles, which served as a beacon for detecting human STAT5B expression. Up
      to 90% quenching efficiency was achieved. Upon hybridizing with the target mRNA,
      the hairpin DNA modified gold nanoparticle beacons (hDAuNP beacons) release the
      fluorophores attached at 5' end of the oligonucleotide sequence. The fluorescence
      properties of the beacon before and after the hybridization with the
      complementary DNA were confirmed in vitro. The stability of hDAuNP beacons
      against degradation by DNase I and GSH indicated that the prepared beacon is
      stable inside cells. The detected fluorescence in MCF-7 cancer cells correlates
      with the specific STAT5B mRNA expression, which is consistent with the result
      from PCR measurement. Fluorescence microscopy showed that the hDAuNP beacons
      internalized in cells without using transfection agents, with intracellular
      distribution in the cytoplasm rather than the nucleus. The results demonstrated
      that this beacon could directly provide quantitative measurement of the
      intracellular STAT5B mRNA in living cells. Compared to the previous approaches,
      this beacon has advantages of higher target to background ratio of detection and
      an increased resistance to nuclease degradation. The strategy reported in this
      study is a promising approach for the intracellular measurement of RNA or protein
      expression in living cells, and has great potential in the study of drug
      screening and discovery.

PMID- 23122231
TI  - Highly sensitive detection of telomerase activity in tumor cells by cascade
      isothermal signal amplification based on three-way junction and base-stacking
      hybridization.
AB  - Herein, We report a simple and highly sensitive telomerase activity assay that
      integrates two consecutive isothermal signal amplification processes, namely,
      three-way junction triggered DNA-machine (3WJ-DNAM), and base-stacking
      hybridization assisted "biological circuit" DNA-machine (BSHBC-DNAM). In the
      presence of telomerase, the 3WJ are formed by the hybridization between the
      telomerase product and 3WJ-probes (3WJ-primer and 3WJ-template), which will
      initiate an autonomous 3WJ-DNAM by multiple processes of replication, nicking,
      and strand displacement, continuously generating short oligonucleotides as
      "triggers". These "triggers" will then provide additional stability for another
      two primers with a shared 5-bp complementary sequence at each 3'-end via base
      stacking hybridization. And the BSHBC-DNAM are subsequently carried out by the
      strand-displacement induced circular utilization of "Trigger". Eventually, the
      single-stranded DNA (ssDNA) is generated in large quantities, and a significant
      fluorescence enhancement is observed due to the hybridization between the ssDNA
      and molecular beacons (MBs). In this way, per telomerase-mediated elongation
      event is efficiently and specifically converted into the greatly amplified
      fluorescence signals. This novel sensing strategy permits measurement of
      telomerase activity in cell extracts over the range of 3-5000 Hela cells, which
      is comparable or even superior to most previously reported methods. Using somatic
      and tumor cell lines, the selectivity and generality of the assay are
      investigated with satisfactory results. Furthermore, the inhibition effect of 3'
      azido-3'-deoxythymidine (AZT) is also investigated, indicating its excellent
      performance in telomerase inhibitor screening.

PMID- 23122233
TI  - America's future.

PMID- 23122232
TI  - Hordeum chilense genome, a useful tool to investigate the endosperm yellow
      pigment content in the Triticeae.
AB  - BACKGROUND: The wild barley Hordeum chilense fulfills some requirements for being
      a useful tool to investigate the endosperm yellow pigment content (YPC) in the
      Triticeae including its diploid constitution, the availability of genetic
      resources (addition and deletion stocks and a high density genetic map) and,
      especially, its high seed YPC not silenced in tritordeums (amphiploids derived
      from H. chilense and wheat). Thus, the aim of this work was to test the utility
      of the H. chilense genome for investigating the YPC in the Triticeae. RESULTS:
      Twelve genes related to endosperm carotenoid content and/or YPC in grasses (Dxr,
      Hdr [synonym ispH], Ggpps1, Psy2, Psy3, Pds, Zds, e-Lcy, b-Lcy, Hyd3, Ccd1 and
      Ppo1) were identified, and mapped in H. chilense using rice genes to identify
      orthologs from barley, wheat, sorghum and maize. Macrocolinearity studies
      revealed that gene positions were in agreement in H. vulgare and H. chilense.
      Additionally, three main regions associated with YPC were identified in
      chromosomes 2Hch, 3Hch and 7Hch in H. chilense, the former being the most
      significant one. CONCLUSIONS: The results obtained are consistent with previous
      findings in wheat and suggest that Ggpps1, Zds and Hyd3 on chromosome 2Hch may be
      considered candidate genes in wheat for further studies in YPC improvement.
      Considering the syntenic location of carotenoid genes in H. chilense, we have
      concluded that the Hch genome may constitute a valuable tool for YPC studies in
      the Triticeae.

PMID- 23122234
TI  - Health risks from toxic pollution.

PMID- 23122235
TI  - Understanding self-harm.

PMID- 23122236
TI  - Global engagement for health could achieve better results now and after 2015.

PMID- 23122238
TI  - Marleen Temmerman: a polymath in reproductive health.

PMID- 23122239
TI  - Effects of physical inactivity on non-communicable diseases.

PMID- 23122242
TI  - Address physical inactivity, but avoid stressing harms.

PMID- 23122244
TI  - The challenge of assessing physical activity in populations.

PMID- 23122246
TI  - Global regional and national causes of child mortality.

PMID- 23122247
TI  - Demographic entrapment is preventing Africa from reaching MDG 1.

PMID- 23122248
TI  - China's one-child policy itself leads to forced abortions.

PMID- 23122249
TI  - Spencer Wells and uterine sutures at caesarean section.

PMID- 23122250
TI  - Amyloid "spells" trouble.

PMID- 23122251
TI  - China's new national standard for drinking water takes effect.

PMID- 23122252
TI  - Teleshopping for health.

PMID- 23122253
TI  - Bifidobacteria may be beneficial to intestinal microbiota and reduction of
      bacterial translocation in mice following ischaemia and reperfusion injury.
AB  - The aim of the present study was to determine the effect of peroral
      bifidobacteria on the intestinal microbiota, barrier function and bacterial
      translocation (BT) in a mouse model of ischaemia and reperfusion (I/R) injury. A
      total of twenty-four male BALB/c mice were randomly allocated into three groups:
      (1) sham-operated, (2) I/R and (3) I/R injury and bifidobacteria pretreatment
      (109 colony-forming units/d). Bifidobacteria were administered daily
      intragastrically for 2 weeks before induction of I/R. Subsequently, samples of
      caecal content, intestinal mucosa, ileal segments, blood, mesenteric lymph nodes
      (MLN) and distant organs (liver, spleen and kidney) were prepared for
      examination. In the I/R model, barrier dysfunction (caecal microbiota dysbiosis,
      disruption of tight junction (TJ), increased epithelial cell apoptosis,
      disruption of mucosa and multiple erosions) in the intestine was observed,
      associated with increased BT to extraintestinal sites. The ratio of BT to MLN and
      distant organs in mice exposed to I/R injury was 62.5 %, which was significantly
      higher than the sham-operated group. However, pretreatment of animals with
      bifidobacteria prevented I/R-induced BT, reduced pro-inflammatory cytokine
      release, the levels of endotoxin, intestinal epithelial cell apoptosis,
      disruption of TJ and increased the concentration of SCFA, resulting in recovered
      microbiota and mucosal integrity. Bifidobacteria may be beneficial in reducing BT
      in I/R injury of mice. Therefore, peroral administration of bifidobacteria is a
      potential strategy to prevent I/R-induced BT and intestinal barrier dysfunction.

PMID- 23122254
TI  - Clinician-patient interaction and health outcome: a potential impact on symptoms
      and quality of life in patients with pain?

PMID- 23122256
TI  - Epidemiology of central nervous system infection.
AB  - In cases of central nervous system infection, it is crucial for the
      neuroradiologist to provide an accurate differential diagnosis of the possible
      pathogens involved so that treating physicians can be aided in the choice of
      empiric therapy. This approach requires the radiologist to be aware of local
      epidemiology and have knowledge of infectious agents that are endemic to their
      area of practice. This article reviews and discusses the changing epidemiology of
      pathogens most often observed in meningitis, brain abscess, epidural abscess,
      postoperative infections, and human immunodeficiency virus infection.

PMID- 23122255
TI  - Development of a set of process and structure indicators for palliative care: the
      Europall project.
AB  - BACKGROUND: By measuring the quality of the organisation of palliative care with
      process and structure quality indicators (QIs), patients, caregivers and policy
      makers are able to monitor to what extent recommendations are met, like those of
      the council of the WHO on palliative care and guidelines. This will support the
      implementation of public programmes, and will enable comparisons between
      organisations or countries. METHODS: As no European set of indicators for the
      organisation of palliative care existed, such a set of QIs was developed. An
      update of a previous systematic review was made and extended with more databases
      and grey literature. In two project meetings with practitioners and experts in
      palliative care the development process of a QI set was finalised and the QIs
      were categorized in a framework, covering the recommendations of the Council of
      Europe. RESULTS: The searches resulted in 151 structure and process indicators,
      which were discussed in steering group meetings. Of those QIs, 110 were eligible
      for the final framework. CONCLUSIONS: We developed the first set of QIs for the
      organisation of palliative care. This article is the first step in a multi step
      project to identify, validate and pilot QIs.

PMID- 23122257
TI  - Imaging of meningitis and ventriculitis.
AB  - Central nervous system infections account for 1% of primary hospital admissions
      and 2% of nosocomial infections and when encountered require prompt diagnosis and
      initiation of specific treatment. Imaging findings are mostly nonspecific with
      respect to the causative pathogen. This article describes the anatomy of cranial
      meninges and extra-axial spaces of the brain. Characteristic findings and recent
      advances in neuroimaging of meningitis and its complications and ventriculitis
      are summarized, and certain noninfectious causes of meningitis and meningitis
      mimics are described.

PMID- 23122258
TI  - Imaging of cerebritis, encephalitis, and brain abscess.
AB  - Imaging plays an important role in the diagnosis and treatment of brain abscess,
      pyogenic infection, and encephalitis. The role of CT and MRI in the diagnosis and
      management of pyogenic brain abscess and its complications is reviewed. The
      imaging appearances of several common and select uncommon infectious
      encephalitides are reviewed. Common causes of encephalitis in immunocompromised
      patients, and their imaging appearances, are also discussed. When combined with
      CSF, serologic studies and patient history, imaging findings can suggest the
      cause of encephalitis.

PMID- 23122259
TI  - Fungal infections of the central nervous system.
AB  - Fungal infections of the central nervous system (CNS) frequently occur in the
      immunocompromised or debilitated host. Imaging findings are non-specific but may
      be organized into extra-axial, parenchymal, and vascular categories. Furthermore,
      knowledge of fungal morphology may predict the imaging manifestations with large,
      hyphal species having a predilection for brain parenchymal involvement, while
      small, unicellular organisms typically result in meningitis. Advanced imaging
      techniques such as diffusion-weighted imaging, MR perfusion and MR spectroscopy,
      when combined with clinical findings, may help in differentiating fungal disease
      from other mimckers such as pyogenic infection or cystic metastases.

PMID- 23122261
TI  - Imaging of neurocysticercosis.
AB  - Neurocysticercosis (NCC) is an infection of the central nervous system by the
      Taenia solium larvae, and is the most common cause of acquired epilepsy in
      endemic regions. The natural history of parenchymal NCC lesions can be divided
      into 4 stages with unique imaging and clinical features. Evaluation of cysticerci
      is challenging on conventional magnetic resonance (MR) imaging and computed
      tomography, and is significantly improved with MR cysternography techniques.
      Differentiation of NCC lesions from metastatic disease and pyogenic abscesses can
      be improved with advanced MR imaging including (1)H nuclear MR spectroscopy,
      diffusion-weighted imaging, and MR perfusion imaging.

PMID- 23122260
TI  - Imaging of rickettsial, spirochetal, and parasitic infections.
AB  - This article is an update and literature review of the clinical and neuroimaging
      findings of the commonly known rickettsial, spirochetal, and eukaryotic parasitic
      infections. Being familiar with clinical presentation and imaging findings of
      these infections is crucial for early diagnosis and treatment especially in
      patients who live in or have a travel history to endemic regions or are
      immunocompromised.

PMID- 23122262
TI  - Central nervous system tuberculosis: pathophysiology and imaging findings.
AB  - With the onset of the human immunodeficiency virus pandemic, the incidence of
      tuberculosis, including central nervous system (CNS) tuberculosis, has increased
      in developed countries. It is no longer a disease confined to underdeveloped and
      developing countries. The imaging appearance has become more complex with the
      onset of multidrug-resistant tuberculosis. Imaging plays an important role in the
      early diagnosis of CNS tuberculosis and may prevent unnecessary morbidity and
      mortality. This article presents an extensive review of typical and atypical
      imaging appearances of intracranial tuberculosis, and discusses pathogenesis,
      patterns of involvement, and advances in imaging of intracranial tuberculosis.

PMID- 23122263
TI  - Pediatric intracranial infections.
AB  - Infection of the central nervous system (CNS) in children is an important entity
      and early recognition is paramount to avoid long-term brain injury, especially in
      very young patients. The causal factors are different in children compared with
      adults and so are the clinical presentations. However, imaging features of CNS
      infection show similar features to those of adults. This article reviews some of
      the common types of pediatric infections, starting with the congenital (or in
      utero) infections followed by bacterial infections of the meninges and brain
      parenchyma.

PMID- 23122264
TI  - Imaging in infections of the head and neck.
AB  - Infections of the head and neck vary in their clinical course and outcome because
      of the diversity of organs and anatomic compartments involved. Imaging plays a
      central role in delineating the anatomic extent of the disease process,
      identifying the infection source, and detecting complications. The utility of
      imaging to differentiate between a solid phlegmonous mass and an abscess cannot
      be overemphasized. This review briefly describes and pictorially illustrates the
      typical imaging findings of some important head and neck infections, such as
      malignant otitis externa, otomastoiditis bacterial and fungal sinusitis, orbital
      cellulitis, sialadenitis, cervical lymphadenitis, and deep neck space infections.

PMID- 23122265
TI  - Spine infections.
AB  - Infections of the spine represent a rare but potentially debilitating and
      neurologically devastating condition for patients. Early diagnosis, imaging, and
      intervention may prevent some of the more critical complications that may ensue
      from this disease process, including alignment abnormalities, central canal
      compromise, nerve root impingement, vascular complications, and spinal cord
      injury. This article reviews the underlying pathophysiologic basis of infection,
      clinical manifestations, and imaging modalities used to diagnose infections of
      the spine and spinal cord.

PMID- 23122266
TI  - Pathologic basis of central nervous system infections.
AB  - Radiology provides valuable gross pathologic information about central nervous
      system (CNS) infections. Major categories of infectious lesions of the brain and
      spinal cord are recognized by imaging such as diffuse, focal, or multifocal. This
      article discusses the pathologic basis of these radiographic findings. It
      illustrates examples with gross and microscopic photographs of CNS infections,
      and the tissue reactions to these infections. Where the organism can spread
      within the CNS, and cellular responses to the organism underlie both the
      radiographic and pathologic findings.

PMID- 23122267
TI  - Neurosurgical aspects of central nervous system infections.
AB  - Infections of the central nervous system (CNS) can be severe, disabling, and
      potentially fatal. Infections of the central nervous system (CNS) can be severe,
      disabling, and potentially fatal. Appropriate recognition of symptoms facilitates
      expeditious evaluation, prompt diagnosis, and timely treatment. Further work-up
      may include cranial or spinal imaging, lumbar puncture, and invasive biopsy.
      Therapy involves antibiotic, antiviral, or antifungal treatment. Surgical
      treatment for debridement, decompression, or reconstruction may also be required.
      This review explores the presentation, pathogenesis, evaluation, and treatment of
      the most common infections of the CNS. Discussion of treatment options also
      includes possible neurosurgical interventions. The infections considered are
      cerebral abscess, subdural empyema, meningitis, encephalitis, toxoplasmosis,
      neurocysticercosis, diskitis, and spinal epidural abscess.

PMID- 23122268
TI  - Neuroimaging Clinics of North America. Central nervous system infections.
      Foreword.

PMID- 23122269
TI  - Neuroimaging Clinics of North America. Central nervous system infections.
      Preface.

PMID- 23122270
TI  - Three dimensional water quality modeling of a shallow subtropical estuary.
AB  - Knowledge of estuarine hydrodynamics and water quality comes mostly from studies
      of large estuarine systems. The processes affecting algae, nutrients, and
      dissolved oxygen (DO) in small and shallow subtropical estuaries are relatively
      less studied. This paper documents the development, calibration, and verification
      of a three dimensional (3D) water quality model for the St. Lucie Estuary (SLE),
      a small and shallow estuary located on the east coast of south Florida. The water
      quality model is calibrated and verified using two years of measured data.
      Statistical analyses indicate that the model is capable of reproducing key water
      quality characteristics of the estuary within an acceptable range of accuracy.
      The calibrated model is further applied to study hydrodynamic and eutrophication
      processes in the estuary. Modeling results reveal that high algae concentrations
      in the estuary are likely caused by excessive nutrient and algae supplies in
      freshwater inflows. While algal blooms may lead to reduced DO concentrations near
      the bottom of the waterbody, this study indicates that stratification and
      circulation induced by freshwater inflows may also contribute significantly to
      bottom water hypoxia in the estuary. It is also found that high freshwater
      inflows from one of the tributaries can change the circulation pattern and
      nutrient loading, thereby impacting water quality conditions of the entire
      estuary. Restoration plans for the SLE ecosystem need to consider both a
      reduction of nutrient loading and regulation of the freshwater discharge pattern.

PMID- 23122271
TI  - The association between farmers' participation in herd health programmes and
      their behaviour concerning treatment of mild clinical mastitis.
AB  - BACKGROUND: In Denmark, it has recently become mandatory for all dairy farmers
      with more than 100 cows to sign up for a herd health programme. Three herd health
      programmes are available. These differ in a number of aspects, including the
      frequency of veterinary visits and the farmer's access to prescription drugs. The
      objective of this study was to investigate whether dairy farmers' behavioural
      intentions, i.e. to call a veterinarian or start medical treatment on the day
      that they detect a cow with mild clinical mastitis (MCM), are different depending
      on the type of herd health programme. METHODS: A questionnaire survey based on
      the Theory of Planned Behaviour (TPB) was conducted. TPB proposes that a person's
      behavioural intention is strongly correlated with his or her actual behaviour.
      Three behavioural factors determine the behavioural intention: attitude,
      subjective norm and perceived behavioural control. Each of these factors is
      decided by a set of beliefs, each of which in turn is weighted by an evaluation:
      1) the expected outcomes of performing the behaviour, 2) what a person believes
      that others think of the behaviour, and 3) the person's perceived power to
      influence the behaviour.A set of statements about the treatment of MCM based on
      interviews with 38 dairy farmers were identified initially. The statements were
      rephrased as questions and the resulting questionnaire was distributed to 400
      randomly selected Danish dairy farmers who use the two most restrictive herd
      health programmes, either Core or Module1, and to all 669 farmers with the least
      restrictive herd health programme, Module2. The association between intention and
      the herd health programme was modelled using logistic regression. RESULTS: The
      farmers with the Module2 herd health programme had a significantly higher
      behavioural intention to perform the behaviour, when compared to farmers with a
      more restrictive herd health programme (OR = 2.1, p < 0.0001). CONCLUSION: Danish
      dairy farmers who participate in Module2 herd health programme had a higher
      intention to treat cases of MCM, compared to farmers who participate in a more
      restrictive herd health programme in which the veterinarian initiates treatments.

PMID- 23122272
TI  - Salt and oxidative stress tolerance in Debaryomyces hansenii and Debaryomyces
      fabryi.
AB  - We report the characterization of five strains belonging to the halotolerant
      highly related Debaryomyces hansenii/fabryi species. The analysis performed
      consisted in studying tolerance properties, membrane characteristics, and cation
      incell amounts. We have specifically investigated (1) tolerance to different
      chemicals, (2) tolerance to osmotic and salt stress, (3) tolerance and response
      to oxidative stress, (4) reactive oxygen species (ROS) content, (5) relative
      membrane potential, (6) cell volume, (7) K(+) and Na(+) ion content, and (8)
      membrane fluidity. Unexpectedly, no direct relationship was found between one
      particular strain, Na(+) content and its tolerance to NaCl or between its ROS
      content and its tolerance to H(2)O(2). Results show that, although in general,
      human origin D. fabryi strains were more resistant to oxidative stress and
      presented shorter doubling times and smaller cell volume than food isolated D.
      hansenii ones, strains belonging to the same species can be significantly
      different. Debaryomyces fabryi CBS1793 strain highlighted for its extremely
      tolerant behavior when exposed to the diverse stress factors studied.

PMID- 23122273
TI  - Room temperature ionic liquids: new GC stationary phases with a novel selectivity
      for flavor and fragrance analyses.
AB  - Ionic liquids (ILs) are of great interest as moderately polar to polar stationary
      phases for GC, because their selectivity differs markedly from that of
      conventionally used phases. In the flavor, fragrance and essential oil fields,
      analysts often deal with complex mixtures of compounds having similar structural
      and physical characteristics (e.g., mono- and sesquiterpenoids), therefore
      requiring an interactive combination between chromatographic and mass spectral
      data for correct identification. New GC stationary phases with different
      selectivity must therefore be continually tested. Performance and evolution over
      time of commercially available IL columns versus those commonly used in these
      fields are here evaluated, mainly in view of their routine use. Chromatographic
      and separative properties (efficiency, separation capability, inertness and/or
      activity) of commercially available IL columns were compared to those of columns
      coated with 5% phenyl-95% methylpolysiloxane, 14% cyanopropyl-86% polysiloxane,
      and polyethylene glycol, on different complexity samples, including standard
      mixtures of volatile suspected allergens and pesticides, and cornmint and vetiver
      essential oils. The results show that IL columns can successfully be used for a
      wide range of applications characteristic of these fields, mainly because of
      their unusual selectivity, in particular when separations based on functional
      groups are required. Moreover, the latest generation of IL columns (IL61 and
      IL60) presents chromatographic performance comparable to or only slightly lower
      than that of the conventional columns routinely used in these fields.

PMID- 23122274
TI  - Extending the detection window of diazepam by directly analyzing its glucuronide
      metabolites in human urine using liquid chromatography-tandem mass spectrometry.
AB  - A method for the simultaneous direct analysis of diazepam oxazepam glucuronide,
      temazepam glucuronide, oxazepam, nordiazepam, and temazepam in human urine was
      developed and validated. Urine sample was purified by solid phase extraction
      (SPE), and the analysis was achieved using a liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) system equipped with an electrospray ionization source
      (ESI). Multiple reaction monitoring (MRM) mode was used to analyze the target
      compounds. Extraction recoveries were 65-122% for all the analytes. The method
      showed acceptable intra-assay and inter-assay precision (both relative standard
      deviation (RSD)<=11.2%) for quality control (QC) samples. The limits of
      detections (LODs) were in the range of 0.1-2 ng/mL. The present assay was applied
      to analyze the urine obtained from three volunteers after oral administration of
      a single dose 5mg of diazepam. The results showed that, the detection periods of
      oxazepam glucuronide and temazepam glucuronide were much longer than diazepam and
      other metabolites.

PMID- 23122275
TI  - Liquid chromatography tandem mass spectrometry method for characterization of
      monoaromatic nitro-compounds in atmospheric particulate matter.
AB  - Nitrogen-containing organic compounds in the atmosphere have drawn attention
      owing to their impact on aerosol chemistry and physics and their potential
      adverse effects on the biosphere. Among them, nitrocatechols and their homologs
      have recently been associated with biomass burning. In the present study,
      nitrocatechols, nitrophenols, nitroguaiacols and nitrosalicylic acids (NSAs) were
      simultaneously quantified for the first time by using a new analytical method
      based on liquid chromatography/tandem mass spectrometry, which was systematically
      optimized and validated. Several analyte specific issues regarding the sample
      preparation and chromatographic analysis were addressed in order to ensure method
      sensitivity, precision, and accuracy. Sample matrix effects were thoroughly
      investigated in order to ensure method specificity. The method was found to be
      sensitive with limits of detection ranging from 0.1 to 1.0 MUg L(-1), and with
      accuracy generally between 90 and 104%. The relative standard deviations for
      repeatability and intermediate precision were better than 4% and 9%,
      respectively. The method was applied to the analysis of winter and summer PM(10)
      samples from the city of Ljubljana, Slovenia. Aerosol concentrations as high as
      152 and 134 ng m(-3) were obtained for the major aerosol nitro-aromatics: 4
      nitrocatechol (4NC) and methyl-nitrocatechols (MNCs), respectively. Up to 500
      times higher concentrations of 4NC and MNCs were found in winter compared to
      summer aerosols. The correlation analysis for winter samples showed that 4NC,
      MNCs, and NSAs are strongly inter-correlated (R(2)=0.84-0.96). Significant
      correlations between these analytes and anhydrosugars support their proposed
      origin from biomass burning. The studied nitro-aromatics were found to constitute
      a non-negligible fraction (around 1%) of the organic carbon.

PMID- 23122276
TI  - Delayed emergence of oseltamivir-resistant seasonal influenza A (H1N1) and
      pandemic influenza A(H1N1)pdm09 viruses in Myanmar.
AB  - The prevalence and timing of emergence of oseltamivir-resistant seasonal and
      pandemic influenza A (H1N1) viruses in Myanmar in 2008 and 2009 are described in
      this report. In 2008, the oseltamivir-resistant seasonal H1N1 virus was detected
      at a lower rate (6%) and emerged at least 2 months later when compared with
      neighboring countries. Similarly, the prevalence of pandemic H1N1 virus was low
      (3%) and the timing of emergence was late (August 2009) in Myanmar.
      Interestingly, we detected three isolates that were resistant to both amantadine
      and oseltamivir. Limited movement of people into the country is attributed to the
      delayed emergence of drug-resistant seasonal and pandemic A(H1N1) viruses.

PMID- 23122277
TI  - Auricular keloid burn.

PMID- 23122278
TI  - Minimally invasive cardiac output monitoring for a parturient with pulmonary
      hypertension.

PMID- 23122279
TI  - Management of a parturient with an anterior sacral meningocele.
AB  - Anterior sacral meningoceles are rare disorders featuring anterior herniation of
      the meninges through a sacral defect or foramen. They are frequently misdiagnosed
      as ovarian or abdominal cysts and surgical exploration has resulted in
      meningitis. In pregnancy it represents an obstacle to delivery of the fetus and
      rupture of the meningocele during vaginal delivery is a significant risk. The
      successful multidisciplinary management of a primiparous patient with an anterior
      sacral meningocele and previous abdominal surgery is presented.

PMID- 23122280
TI  - Choice of anaesthetic agents for caesarean section: a UK survey of current
      practice.
AB  - BACKGROUND: A national survey of current practice and preferred drug choices for
      both induction and maintenance of general anaesthesia for caesarean section was
      undertaken. METHODS: Following approval by the Obstetric Anaesthetists'
      Association, all UK consultant members were invited to respond to an electronic
      survey. RESULTS: The response rate was 56% (691/1228). Ninety-three percent of
      respondents use thiopental for induction: 58% (15% definitely and 44% probably)
      would support a change to propofol for induction. Thiopental was used in most
      cases for historical reasons (37%) or to reduce awareness (31%); other
      considerations included a clear end-point, dose predictability, cardiovascular
      stability, effects on the baby and drug licence concerns. Fifty-seven percent
      indicated that their trainees were encouraged to use thiopental for non-obstetric
      anaesthesia. Fifteen percent of respondents use opioids during rapid-sequence
      induction. Eighty-five percent use nitrous oxide; 53% of respondents use
      sevoflurane (51.6%) or desflurane (1.6%) for maintenance of anaesthesia, and this
      would increase to over 80% if financial constraints were removed. CONCLUSION: Our
      survey suggests that while thiopental remains the induction agent of choice in
      the UK, a reasonable body of medical opinion would support a change to propofol
      for induction. This is reassuring as thiopental becomes more difficult and
      expensive to obtain.

PMID- 23122281
TI  - Electrical impedance tomography may optimize ventilation in a postpartum woman
      with respiratory failure.
AB  - Amniotic fluid embolism is a rare peripartum complication with the sudden onset
      of haemodynamic instability, respiratory failure and coagulopathy during labour
      or soon after delivery. A 31-year-old woman with amniotic fluid embolism was
      treated with vasopressors, inotropes, intravenous fluid, tranexamic acid and
      ventilatory support. Assessment of respiratory impairment was made using
      conventional chest X-ray, computed tomography and electrical impedance
      tomography. The potential for electrical impedance tomography to improve
      monitoring and guide respiratory therapy is explored.

PMID- 23122282
TI  - Maps for changing landscapes: viewing epigenomic signatures through
      differentiation.
AB  - Enormous progress has been made in identifying chromatin "signatures" that define
      tissue-specific transcriptional networks. Three recent studies by Rada-Iglesias
      et al. (2012), Wamstad et al. (2012), and Paige et al. (2012) track such
      signatures during cellular differentiation, revealing a richer understanding of
      gene regulation and providing hints of new phenomena.

PMID- 23122283
TI  - Stressed out: endogenous aldehydes damage hematopoietic stem cells.
AB  - Despite a well-defined role for the Fanconi anemia (FA) pathway in mediating DNA
      repair, the mechanisms underlying the bone marrow failure in FA patients are
      poorly defined. Recently in Nature, Garaycoechea et al. (2012), identify aldehyde
      mediated genotoxicity of hematopoietic stem cells as a cause for bone marrow
      failure.

PMID- 23122284
TI  - Stem cell therapy for male infertility takes a step forward.
AB  - The feasibility of using spermatogonial stem cells (SSCs) for cell-based
      infertility treatment has suffered from a lack of evidence in a preclinical
      nonhuman primate model. In this issue, Hermann et al. (2012) demonstrate that
      autologous and allogeneic transplantation of SSCs in testes of rhesus macaques
      produced functional sperm.

PMID- 23122285
TI  - Cellular transplantation into lymph nodes may not be such a crazy idea.
AB  - A study published in Nature Biotechnology by Komori and colleagues (Komori et
      al., 2012) has identified the surprising potential of lymph nodes as sites for
      cellular transplants.

PMID- 23122286
TI  - Metabolic regulation in pluripotent stem cells during reprogramming and self
      renewal.
AB  - Small, rapidly dividing pluripotent stem cells (PSCs) have unique energetic and
      biosynthetic demands compared with typically larger, quiescent differentiated
      cells. Shifts between glycolysis and oxidative phosphorylation with PSC
      differentiation or reprogramming to pluripotency are accompanied by changes in
      cell cycle, biomass, metabolite levels, and redox state. PSC and cancer cell
      metabolism are overtly similar, with metabolite levels influencing
      epigenetic/genetic programs. Here, we discuss the emerging roles for metabolism
      in PSC self-renewal, differentiation, and reprogramming.

PMID- 23122288
TI  - Stem cells in the land of the rising sun: ISSCR 2012.
AB  - The 2012 annual meeting of the International Society for Stem Cell Research
      (ISSCR) marked the Tenth Anniversary of the ISSCR. Held in Japan, the meeting
      showcased recent discoveries and surveyed the remarkable progress that has been
      made in a decade of stem cell research.

PMID- 23122287
TI  - Metabolic plasticity in stem cell homeostasis and differentiation.
AB  - Plasticity in energy metabolism allows stem cells to match the divergent demands
      of self-renewal and lineage specification. Beyond a role in energetic support,
      new evidence implicates nutrient-responsive metabolites as mediators of crosstalk
      between metabolic flux, cellular signaling, and epigenetic regulation of cell
      fate. Stem cell metabolism also offers a potential target for controlling tissue
      homeostasis and regeneration in aging and disease. In this Perspective, we cover
      recent progress establishing an emerging relationship between stem cell
      metabolism and cell fate control.

PMID- 23122289
TI  - Ezh1 is required for hematopoietic stem cell maintenance and prevents senescence
      like cell cycle arrest.
AB  - Polycomb group (PcG) proteins are key epigenetic regulators of hematopietic stem
      cell (HSC) fate. The PcG members Ezh2 and Ezh1 are important determinants of
      embryonic stem cell identity, and the transcript levels of these histone
      methyltransferases are inversely correlated during development. However, the role
      of Ezh1 in somatic stem cells is largely unknown. Here we show that Ezh1
      maintains repopulating HSCs in a slow-cycling, undifferentiated state, protecting
      them from senescence. Ezh1 ablation induces significant loss of adult HSCs, with
      concomitant impairment of their self-renewal capacity due to a potent senescence
      response. Epigenomic and gene expression changes induced by Ezh1 deletion in
      senesced HSCs demonstrated that Ezh1-mediated PRC2 activity catalyzes
      monomethylation and dimethylation of H3K27. Deletion of Cdkn2a on the Ezh1 null
      background rescued HSC proliferation and survival. Our results suggest that Ezh1
      is an important histone methyltransferase for HSC maintenance.

PMID- 23122290
TI  - Mouse embryonic head as a site for hematopoietic stem cell development.
AB  - In the mouse embryo, the aorta-gonad-mesonephros (AGM) region is considered to be
      the sole location for intraembryonic emergence of hematopoietic stem cells
      (HSCs). Here we report that, in parallel to the AGM region, the E10.5-E11.5 mouse
      head harbors bona fide HSCs, as defined by long-term, high-level, multilineage
      reconstitution and self-renewal capacity in adult recipients, before HSCs enter
      the circulation. The presence of hemogenesis in the midgestation head is
      indicated by the appearance of intravascular cluster cells and the blood-forming
      capacity of a sorted endothelial cell population. In addition, lineage tracing
      via an inducible VE-cadherin-Cre transgene demonstrates the hemogenic capacity of
      head endothelium. Most importantly, a spatially restricted lineage labeling
      system reveals the physiological contribution of cerebrovascular endothelium to
      postnatal HSCs and multilineage hematopoiesis. We conclude that the mouse
      embryonic head is a previously unappreciated site for HSC emergence within the
      developing embryo.

PMID- 23122291
TI  - Notch and TGFbeta form a reciprocal positive regulatory loop that suppresses
      murine prostate basal stem/progenitor cell activity.
AB  - The role of Notch signaling in the maintenance of adult murine prostate
      epithelial homeostasis remains unclear. We found that Notch ligands are mainly
      expressed within the basal cell lineage, while active Notch signaling is detected
      in both the prostate basal and luminal cell lineages. Disrupting the canonical
      Notch effector Rbp-j impairs the differentiation of prostate basal stem cells and
      increases their proliferation in vitro and in vivo, but does not affect luminal
      cell biology. Conversely, ectopic Notch activation in adult prostates results in
      a decrease in basal cell number and luminal cell hyperproliferation. TGFbeta
      dominates over Notch signaling and overrides Notch ablation-induced proliferation
      of prostate basal cells. However, Notch confers sensitivity and positive feedback
      by upregulating a plethora of TGFbeta signaling components including TgfbetaR1.
      These findings reveal crucial roles of the self-enforced positive reciprocal
      regulatory loop between TGFbeta and Notch in maintaining prostate basal stem cell
      dormancy.

PMID- 23122292
TI  - A self-limiting switch based on translational control regulates the transition
      from proliferation to differentiation in an adult stem cell lineage.
AB  - In adult stem cell lineages, progenitor cells commonly undergo mitotic transit
      amplifying (TA) divisions before terminal differentiation, allowing production of
      many differentiated progeny per stem cell division. Mechanisms that limit TA
      divisions and trigger the switch to differentiation may protect against cancer by
      preventing accumulation of oncogenic mutations in the proliferating population.
      Here we show that the switch from TA proliferation to differentiation in the
      Drosophila male germline stem cell lineage is mediated by translational control.
      The TRIM-NHL tumor suppressor homolog Mei-P26 facilitates accumulation of the
      differentiation regulator Bam in TA cells. In turn, Bam and its partner Bgcn bind
      the mei-P26 3' untranslated region and repress translation of mei-P26 in late TA
      cells. Thus, germ cells progress through distinct, sequential regulatory states,
      from Mei-P26 on/Bam off to Bam on/Mei-P26 off. TRIM-NHL homologs across species
      facilitate the switch from proliferation to differentiation, suggesting a
      conserved developmentally programmed tumor suppressor mechanism.

PMID- 23122293
TI  - The transcriptional landscape of hematopoietic stem cell ontogeny.
AB  - Transcriptome analysis of adult hematopoietic stem cells (HSCs) and their progeny
      has revealed mechanisms of blood differentiation and leukemogenesis, but a
      similar analysis of HSC development is lacking. Here, we acquired the
      transcriptomes of developing HSCs purified from >2,500 murine embryos and adult
      mice. We found that embryonic hematopoietic elements clustered into three
      distinct transcriptional states characteristic of the definitive yolk sac, HSCs
      undergoing specification, and definitive HSCs. We applied a network-biology-based
      analysis to reconstruct the gene regulatory networks of sequential stages of HSC
      development and functionally validated candidate transcriptional regulators of
      HSC ontogeny by morpholino-mediated knockdown in zebrafish embryos. Moreover, we
      found that HSCs from in vitro differentiated embryonic stem cells closely
      resemble definitive HSCs, yet lack a Notch-signaling signature, likely accounting
      for their defective lymphopoiesis. Our analysis and web resource will enhance
      efforts to identify regulators of HSC ontogeny and facilitate the engineering of
      hematopoietic specification.

PMID- 23122295
TI  - Dissecting tocopherols content in maize (Zea mays L.), using two segregating
      populations and high-density single nucleotide polymorphism markers.
AB  - BACKGROUND: Tocopherols, which are vitamin E compounds, play an important role in
      maintaining human health. Compared with other staple foods, maize grains contain
      high level of tocopherols. RESULTS: Two F(2) populations (K22/CI7 and K22/Dan340,
      referred to as POP-1 and POP-2, respectively), which share a common parent (K22),
      were developed and genotyped using a GoldenGate assay containing 1,536 single
      nucleotide polymorphism (SNP) markers. An integrated genetic linkage map was
      constructed using 619 SNP markers, spanning a total of 1649.03 cM of the maize
      genome with an average interval of 2.67 cM. Seventeen quantitative trait loci
      (QTLs) for all the traits were detected in the first map and 13 in the second. In
      these two maps, QTLs for different traits were localized to the same genomic
      regions and some were co-located with candidate genes in the tocopherol
      biosynthesis pathway. Single QTL was responsible for 3.03% to 52.75% of the
      phenotypic variation and the QTLs in sum explained 23.4% to 66.52% of the total
      phenotypic variation. A major QTL (qc5-1/qd5-1) affecting alpha-tocopherol
      (alphaT) was identified on chromosome 5 between the PZA03161.1 and PZA02068.1 in
      the POP-2. The QTL region was narrowed down from 18.7 Mb to 5.4 Mb by estimating
      the recombination using high-density markers of the QTL region. This allowed the
      identification of the candidate gene VTE4 which encodes gamma-tocopherol
      methyltransferase, an enzyme that transforms gamma-tocopherol (gammaT)to alphaT.
      CONCLUSIONS: These results demonstrate that a few QTLs with major effects and
      several QTLs with medium to minor effects might contribute to the natural
      variation of tocopherols in maize grain. The high-density markers will help to
      fine map and identify the QTLs with major effects even in the preliminary
      segregating populations. Furthermore, this study provides a simple guide line for
      the breeders to improve traits that minimize the risk of malnutrition, especially
      in developing countries.

PMID- 23122296
TI  - Experiences, opportunities and challenges of implementing task shifting in
      underserved remote settings: the case of Kongwa district, central Tanzania.
AB  - BACKGROUND: Tanzania is experiencing acute shortages of Health Workers (HWs), a
      situation which has forced health managers, especially in the underserved
      districts, to hastily cope with health workers' shortages by adopting task
      shifting. This has however been due to limited options for dealing with the
      crisis of health personnel. There are on-going discussions in the country on
      whether to scale up task shifting as one of the strategies for addressing health
      personnel crisis. However, these discussions are not backed up by rigorous
      scientific evidence. The aim of this paper is two-fold. Firstly, to describe the
      current situation of implementing task shifting in the context of acute shortages
      of health workers and, secondly, to provide a descriptive account of the
      potential opportunities or benefits and the likely challenges which might ensue
      as a result of implementing task shifting. METHODS: We employed in-depth
      interviews with informants at the district level and supplemented the information
      with additional interviews with informants at the national level. Interviews
      focussed on the informants' practical experiences of implementing task shifting
      in their respective health facilities (district level) and their opinions
      regarding opportunities and challenges which might be associated with
      implementation of task shifting practices. At the national level, the main focus
      was on policy issues related to management of health personnel in the context of
      implementation of task shifting, in addition to seeking their opinions and
      perceptions regarding opportunities and challenges of implementing task shifting
      if formally adopted. RESULTS: Task shifting has been in practice for many years
      in Tanzania and has been perceived as an inevitable coping mechanism due to
      limited options for addressing health personnel shortages in the country.
      Majority of informants had the concern that quality of services is likely to be
      affected if appropriate policy infrastructures are not in place before
      formalising tasks shifting. There was also a perception that implementation of
      task shifting has ensured access to services especially in underserved remote
      areas. Professional discontent and challenges related to the management of health
      personnel policies were also perceived as important issues to consider when
      implementing task shifting practices. Additional resources for additional
      training and supervisory tasks were also considered important in the
      implementation of task shifting in order to make it deliver much the same way as
      it is for conventional modalities of delivering care. CONCLUSIONS: Task shifting
      implementation occurs as an ad hoc coping mechanism to the existing shortages of
      health workers in many undeserved areas of the country, not just in the study
      site whose findings are reported in this paper. It is recommended that the most
      important thing to do now is not to determine whether task shifting is possible
      or effective but to define the limits of task shifting so as to reach a consensus
      on where it can have the strongest and most sustainable impact in the delivery of
      quality health services. Any action towards this end needs to be evidence-based.

PMID- 23122294
TI  - Spermatogonial stem cell transplantation into rhesus testes regenerates
      spermatogenesis producing functional sperm.
AB  - Spermatogonial stem cells (SSCs) maintain spermatogenesis throughout a man's life
      and may have application for treating some cases of male infertility, including
      those caused by chemotherapy before puberty. We performed autologous and
      allogeneic SSC transplantations into the testes of 18 adult and 5 prepubertal
      recipient macaques that were rendered infertile with alkylating chemotherapy.
      After autologous transplant, the donor genotype from lentivirus-marked SSCs was
      evident in the ejaculated sperm of 9/12 adult and 3/5 prepubertal recipients
      after they reached maturity. Allogeneic transplant led to donor-recipient
      chimerism in sperm from 2/6 adult recipients. Ejaculated sperm from one recipient
      transplanted with allogeneic donor SSCs were injected into 85 rhesus oocytes via
      intracytoplasmic sperm injection. Eighty-one oocytes were fertilized, producing
      embryos ranging from four-cell to blastocyst with donor paternal origin confirmed
      in 7/81 embryos. This demonstration of functional donor spermatogenesis following
      SSC transplantation in primates is an important milestone for informed clinical
      translation.

PMID- 23122297
TI  - Early-season predation on aphids by winter-active spiders in apple orchards
      revealed by diagnostic PCR.
AB  - Aphids are major pests in apple orchards, debilitating the crop and spreading
      disease. We investigated whether early-season predation by canopy spiders may be
      effectively controlling aphid numbers in three organic orchards. For this
      purpose, we monitored the aphid population dynamics from the winter eggs to
      colony stages and compared this to spider abundances and rates of predation on
      aphids detected by diagnostic polymerase chain reaction. For the latter, we
      applied existing general aphid primers. We found that spiders ate colony
      fundatrices and that aphid numbers were negatively related to spider abundance.
      Spiders were the main active predators within the orchards when the first colony
      fundatrices were present, indicating their importance in the early control of
      aphid populations.

PMID- 23122298
TI  - Raised jugular venous pressure intensifies release of brain injury biomarkers in
      patients undergoing cardiac surgery.
AB  - OBJECTIVES: Neurologic damage after cardiac surgery with extracorporeal
      circulation is multifactorial. Despite several studies, its pathophysiology is
      poorly understood. The purpose of this study was to determine the changes in
      jugular venous pressure and to analyze their effect on perioperative brain injury
      measured by biomarkers in patients undergoing coronary artery bypass grafting.
      DESIGN: Observational study. SETTING: Department of cardiac surgery in a medical
      university hospital. PARTICIPANTS: Adult patients undergoing elective coronary
      artery bypass grafting with extracorporeal circulation under general anesthesia.
      INTERVENTIONS: The right jugular vein was cannulated in retrograde fashion.
      Jugular venous pressure was measured in the jugular vein bulb (JVBP).
      Concentrations of plasma glial fibrillary acidic protein, tau protein,
      arteriovenous lactate, and jugular vein saturation were measured as the markers
      of brain injury during the surgery and early postoperative period. All were
      analyzed in relation to JVBP. MEASUREMENTS AND MAIN RESULTS: Increased JVBP was
      noted after extracorporeal circulation and after surgery. A significant increase
      >12 mmHg for JVBP, increased plasma glial fibrillary acidic protein, tau protein,
      arteriovenous lactate concentrations, and decreased jugular vein saturation were
      observed. CONCLUSIONS: Cardiac surgery increased JVBP and an increased JVBP > 12
      mmHg intensified an increase in brain injury biomarker concentrations.

PMID- 23122300
TI  - A practical approach to echocardiographic assessment of perioperative diastolic
      dysfunction.
AB  - The Doppler assessment of diastolic dysfunction (DD) is not part of a standard
      comprehensive intraoperative echocardiographic examination. Although the reasons
      may be many, the lack of a simplified algorithm for the assessment of DD specific
      to the perioperative arena, the implications of this diagnosis on clinical care,
      and the absence of therapeutic options are some of the commonly cited reasons. In
      this article, the authors address these possible reasons for the lack of routine
      application of Doppler indices to assess perioperative DD. The authors have
      chosen to highlight some of the most common conceptual questions, which often
      have been raised by anesthesiologists, and attempted to suggest answers. Drawing
      from their experience and data, the authors propose a simplified algorithm for
      the application of Doppler to assess and diagnose DD with an individualized and a
      mechanistic approach. The proposed algorithm is from within the premise of the
      published guidelines and attempts to simplify the perioperative approach. The
      authors hope this approach will be simple enough for routine application to
      affect therapy and a tangible change in outcome. The authors suggest that
      knowledge of left atrial size is valuable as a marker for persistently increased
      left ventricular end-diastolic pressure and its possible role in risk
      stratification.

PMID- 23122299
TI  - Cerebral blood flow autoregulation is preserved after continuous-flow left
      ventricular assist device implantation.
AB  - OBJECTIVE: To compare cerebral blood flow (CBF) autoregulation in patients
      undergoing continuous-flow left ventricular assist device (LVAD) implantation
      with that in patients undergoing coronary artery bypass grafting (CABG). DESIGN:
      Prospective, observational, controlled study. SETTING: Academic medical center.
      PARTICIPANTS: Fifteen patients undergoing LVAD insertion and 10 patients
      undergoing CABG. MEASUREMENTS AND MAIN RESULTS: Cerebral autoregulation was
      monitored with transcranial Doppler and near-infrared spectroscopy. A continuous
      Pearson correlation coefficient was calculated between mean arterial pressure
      (MAP) and CBF velocity and between MAP and near-infrared spectroscopic data,
      rendering the variables mean velocity index (Mx) and cerebral oximetry index
      (COx), respectively. Mx and COx approach 0 when autoregulation is intact (no
      correlation between CBF and MAP), but approach 1 when autoregulation is impaired.
      Mx was lower during and immediately after cardiopulmonary bypass in the LVAD
      group than in the CABG group, indicating better-preserved autoregulation. Based
      on COx monitoring, autoregulation tended to be better preserved in the LVAD group
      than in the CABG group immediately after surgery (p = 0.0906). On postoperative
      day 1, COx was lower in the LVAD group than in the CABG group, indicating
      preserved CBF autoregulation (p = 0.0410). Based on COx monitoring, 3 patients
      (30%) in the CABG group had abnormal autoregulation (COx >=0.3) on the first
      postoperative day but no patient in the LVAD group had this abnormality (p =
      0.037). CONCLUSIONS: These data suggest that CBF autoregulation is preserved
      during and immediately after surgery in patients undergoing LVAD insertion.

PMID- 23122301
TI  - MATLAB-implemented estimation procedure for model-based assessment of hepatic
      insulin degradation from standard intravenous glucose tolerance test data.
AB  - Present study provides a novel MATLAB-based parameter estimation procedure for
      individual assessment of hepatic insulin degradation (HID) process from standard
      frequently-sampled intravenous glucose tolerance test (FSIGTT) data. Direct
      access to the source code, offered by MATLAB, enabled us to design an
      optimization procedure based on the alternating use of Gauss-Newton's and
      Levenberg-Marquardt's algorithms, which assures the full convergence of the
      process and the containment of computational time. Reliability was tested by
      direct comparison with the application, in eighteen non-diabetic subjects, of
      well-known kinetic analysis software package SAAM II, and by application on
      different data. Agreement between MATLAB and SAAM II was warranted by intraclass
      correlation coefficients >=0.73; no significant differences between corresponding
      mean parameter estimates and prediction of HID rate; and consistent residual
      analysis. Moreover, MATLAB optimization procedure resulted in a significant 51%
      reduction of CV% for the worst-estimated parameter by SAAM II and in maintaining
      all model-parameter CV% <20%. In conclusion, our MATLAB-based procedure was
      suggested as a suitable tool for the individual assessment of HID process.

PMID- 23122302
TI  - A data mining system for providing analytical information on brain tumors to
      public health decision makers.
AB  - Cancer is the leading cause of death in economically developed countries and the
      second leading cause of death in developing countries. Malignant brain neoplasms
      are among the most devastating and incurable forms of cancer, and their treatment
      may be excessively complex and costly. Public health decision makers require
      significant amounts of analytical information to manage public treatment programs
      for these patients. Data mining, a technology that is used to produce
      analytically useful information, has been employed successfully with medical
      data. However, the large-scale adoption of this technique has been limited thus
      far because it is difficult to use, especially for non-expert users. One way to
      facilitate data mining by non-expert users is to automate the process. Our aim is
      to present an automated data mining system that allows public health decision
      makers to access analytical information regarding brain tumors. The emphasis in
      this study is the use of ontology in an automated data mining process. The non
      experts who tried the system obtained useful information about the treatment of
      brain tumors. These results suggest that future work should be conducted in this
      area.

PMID- 23122305
TI  - Cytotoxicity and apoptosis induction in human HepG2 hepatoma cells by
      decabromodiphenyl ethane.
AB  - OBJECTIVE: To investigate the toxic effects of decabromodiphenyl ethane (DBDPE),
      used as an alternative to decabromodiphenyl ether in vitro. METHODS: HepG2 cells
      were cultured in the presence of DBDPE at various concentrations (3.125-100.0
      mg/L) for 24, 48, and 72 h respectively and the toxic effect of DBDPE was
      studied. RESULTS: As evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide and lactate dehydrogenase assays and nuclear morphological
      changes, DBDPE inhibited HepG2 viability in a time- and dose-dependent manner
      within a range of 12.5 mg/L to 100 mg/L and for 48 h and 72 h. Induction of
      apoptosis was detected at 12.5-100 mg/L at 48 h and 72 h by propidium iodide
      staining, accompanied with overproduction of reactive oxygen species (ROS).
      Furthermore, N-acetyl-L-cysteine, a widely used ROS scavenger, significantly
      reduced DBDPE-induced ROS levels and increased HepG2 cells viability. CONCLUSION:
      DBDPE has cytotoxic and anti-proliferation effect and can induce apoptosis in
      which ROS plays an important role.

PMID- 23122304
TI  - Deletion of Orai1 alters expression of multiple genes during osteoclast and
      osteoblast maturation.
AB  - Store-operated Ca(2+) entry (SOCE) is a major Ca(2+) influx pathway in most non
      excitable cell types and Orai1 was recently identified as an essential pore
      subunit of SOCE channels. Here we investigate the physiological role of Orai1 in
      bone homeostasis using Orai1-deficient mice (Orai1(-/-)). Orai1(-/-) mice
      developed osteopenia with decreased bone mineral density and trabecular bone
      volume. To identify the nature and origin of the bone defect, bone-resorbing
      osteoclasts and bone-forming osteoblasts from Orai1(-/-) mice were examined.
      Orai1-mediated SOCE was completely abolished in Orai1(-/-) osteoclast precursor
      cells and osteoclastogenesis in vitro from Orai1(-/-) mice was impaired due to a
      defect in cell fusion of pre-osteoclasts. Also, resorption activity in vitro was
      comparable but the size of pits formed by Orai1(-/-) osteoclasts was smaller. We
      next assessed the role of Orai1 in osteoblast differentiation and function by
      using a pre-osteoblast cell line, as well as primary osteoblasts from wild-type
      and Orai1(-/-) mice. SOCE in MC3T3-E1 pre-osteoblastic cells was inactivated by
      lentiviral overexpression of a pore-dead Orai1 mutant. Lack of SOCE in MC3T3-E1
      had no effect on alkaline phosphatase staining and expression but substantially
      inhibited mineralized nodule formation. Consistent with this finding, Orai1
      mediated SOCE was markedly reduced in Orai1(-/-) osteoblast precursor cells and
      osteoblastogenesis in vitro from Orai1(-/-) stromal cells showed impaired mineral
      deposition but no change in differentiation. This indicates that Orai1 is
      involved in the function but not in the differentiation of osteoblasts. Together,
      these results suggest that Orai1 plays a critical role in bone homeostasis by
      regulating both osteoblasts and osteoclasts.

PMID- 23122306
TI  - Assessment of iron bioavailability in ten kinds of Chinese wheat flours using an
      in vitro digestion/Caco-2 cell model.
AB  - OBJECTIVE: To compare iron bioavailability (Fe BV) from ten selected kinds of
      Chinese wheat flours in order to provide scientific basis for further human
      trials and enable plant breeding programs to screen biofortified wheat cultivars.
      METHODS: An in vitro digestion/Caco-2 cell model was used to assess Fe BV of ten
      flour samples from six leading Chinese wheat cultivars and the stability of Fe BV
      in one cultivar was studied across three growing environments. RESULTS:
      Significant differences were observed in both Fe BV and Fe bioavailability per
      gram of food (Fe BVPG) among cultivars (P<0.01) grown at the same location with
      the same flour extraction rate. Zhongyou 9507 and Jingdong 8 had Fe BV 37%-54%
      and Fe BVPG 103%-154% higher than the reference control. In the Anyang
      environment, Zhongyou 9507 had a higher wheat flour-Fe level and Fe BVPG.
      Differences in Fe BV were detected in cultivars with different flour extraction
      rates. CONCLUSION: Zhongyou 9507 and Jingdong 8 were identified as the most
      promising cultivars for further evaluation of efficacy by using human subjects.
      The growing environments had no effect on Fe BV, but did have a significant
      effect on Fe BVPG. Fe bioavailabilities in low-extraction (40%) flours were
      higher than those in high-extraction (78%) flours.

PMID- 23122307
TI  - Inactivated Sendai virus suppresses murine melanoma growth by inducing host
      immune responses and down-regulating beta-catenin expression.
AB  - OBJECTIVE: This paper aims to investigate the anti-tumor mechanism of inactivated
      Sendai virus (Hemagglutinating virus of Japan envelope, HVJ-E) for murine
      melanoma (B16F10). METHODS: The murine dendritic cells (DCs) were treated with
      HVJ-E, and then the cytokines secreted from DCs and costimulation-related
      molecules on DCs were measured. Meanwhile, the expression of beta-catenin in HVJ
      E treated murine melanoma cells was detected. In addition, HVJ-E was
      intratumorally injected into the melanoma on C57BL/6 mice, and the immune cells,
      CTL response and tumor volume were analyzed. RESULTS: HVJ-E injected into B16F10
      melanoma obviously inhibited the growth of the tumor and prolonged the survival
      time of the tumor-bearing mice. Profiles of cytokines secreted by dendritic cells
      (DCs) after HVJ-E stimulation showed that the number of cytokines released was
      significantly higher than that elicited by PBS (1P<0.05). The co-stimulation
      related molecules on DCs were comparable to those stimulated by LPS.
      Immunohistochemical examinations demonstrated the repression of beta-catenin in
      B16F10 melanoma cells after HVJ-E treatment. Meanwhile, real-time reverse
      transcription PCR revealed that HVJ-E induced a remarkable infiltration of CD11c
      positive cells, chemokine ligand 10 (CXCL10) molecules, interleukin-2 (IL-2)
      molecule, CD4(+) and CD8(+) T cells into HVJ-E injected tumors. Furthermore, the
      mRNA expression level of beta-catenin in the HVJ-E injected tumors was also down
      regulated. In addition, B16F10-specific CTLs were induced significantly after HVJ
      E was injected into the tumor-bearing mice. CONCLUSION: This is the first report
      to show the effective inhibition of melanoma tumors by HVJ-E alone and the
      mechanism through which it induces antitumor immune responses and regulates
      important signal pathways for melanoma invasion. Therefore, HVJ-E shows its
      prospect as a novel therapeutic for melanoma therapy.

PMID- 23122308
TI  - TNF-alpha and IL-1RA polymorphisms and silicosis susceptibility in Chinese
      workers exposed to silica particles: a case-control study.
AB  - OBJECTIVE: To assess the association of TNF-alpha and IL-1RA SNPs with the risk
      of silicosis in Chinese workers exposed to silica particles. METHODS: Case
      control study design was used to enroll 68 silicotic patients induced by silica
      particles and 68 healthy workers matched for length of silica particle exposure
      as controls. Both cases and controls were from the same company in southwest
      China, and each of them was requested to complete a questionnaire. Blood samples
      were drawn for genomic DNA extraction from each participant. The genotyping of
      TNF-alpha (-238 and -308) and IL-1RA (+2018) was performed using polymerase chain
      reaction-based restriction fragment length polymorphism (PCR-RFLP) and SYBR green
      based quantitative polymerase chain reaction (qPCR), respectively. Unconditional
      logistic regression model was used to estimate odds ratios (ORs) and their 95%
      confidential intervals (CI) for SNPs. RESULTS: No significant differences were
      found between cases and controls in particles exposure length, body mass index
      (BMI), and status of smoking and alcohol consumption except for age (P=0.001) and
      blood type (P=0.042). The frequencies of TNF-alpha (-238) and IL-1RA (+2018)
      genotypes in cases were significantly different from those in controls, (P=0.001
      and P=0.002, respectively), while a borderline significant difference was found
      in the frequencies of TNF-alpha (-308) between cases and controls (P=0.063). The
      variants of three SNPs increased the risk of silicosis in the Chinese workers
      exposed to silica particles. The adjusted ORs of TNF-alpha (-308), TNF-alpha (
      238) and IL-1RA (+2018) were 2.8 (95% CI: 1.1-7.5), 20.9 (95% CI: 1.8-236.4) and
      4.0 (95% CI: 1.6-10.1), respectively. CONCLUSION: It is suggested that cytokine
      polymorphisms of TNF-alpha (-238, -308) and IL-1RA (+2018) are associated with
      the risk of silicosis in the Chinese workers exposed to silica particles. Further
      independent studies on the interaction between SNPs and exposure to silica
      particles with a larger sample size are therefore warranted.

PMID- 23122309
TI  - The relationship between polymorphisms at 17 gene sites and hypertension among
      the Aboriginal Tibetan people.
AB  - OBJECTIVE: The incidence of hypertension in Tibet ranks highest among all Chinese
      provinces. This may be due to genetic changes caused by Tibet's unique natural
      environment and agrarian lifestyle, prompting us to investigated the relationship
      between gene polymorphisms and hypertension. METHODS: Blood samples were
      collected from 229 hypertensive participants and 372 healthy (control)
      participants from five Tibetan counties. Seventeen single nucleotide
      polymorphisms were investigated for their connection to hypertension. RESULTS:
      The C allele at rs2070744 of the NOS3 gene was shown to be significantly
      associated with hypertension (P=0.0443; OR=1.636). Additionally, the T allele of
      rs4961 of the ADD gene was correlated with hypertension in women (P=0.03124;
      OR=1.584). CONCLUSION: In this study we found that the NOS3 and ADD genes were
      related to a high incidence of hypertension among Tibetans. NOS3 gene plays a
      role in regulating vascular tone and blood vessel diameter, which may be altered
      by the low-oxygen environment of Tibet. ADD is involved in water and salt
      metabolism, which is consistent with the high-salt diet of Tibetans. The
      correlations elucidated by our study were different from those of other ethnic
      groups, indicating that these findings may be specific to the Tibetan people.

PMID- 23122310
TI  - Identification of two novel mitochondrial DNA deletions induced by ionizing
      radiation.
AB  - OBJECTIVE: We identify ionizing radiation-induced mitochondrial DNA (mtDNA)
      deletions in human lymphocytes and their distribution in normal populations.
      METHODS: Long-range polymerase chain reactions (PCR) using two pairs of primers
      specific for the human mitochondrial genome were used to analyze the
      lymphoblastoid cell line following exposure to 10 Gy (60)Co gamma-rays. Limited
      condition PCR, cloning and sequencing techniques were applied to verify the mtDNA
      deletions detected with long-range PCR. Human peripheral blood samples were
      irradiated with 0, 2 and 6 Gy (60)Co gamma-rays, and real-time PCR analysis was
      performed to validate the mtDNA deletions. In order to know the distribution of
      mtDNA deletions in normal population, 222 healthy Chinese adults were also
      investigated. RESULTS: Two mtDNA deletions, a 7455-bp deletion (nt475-nt7929 in
      heavy strand) and a 9225-bp deletion (nt7714 -nt369 in heavy strand), occurring
      between two 8-bp direct repeats, were identified in lymphoblastoid cells using
      long-range PCR, limited-condition PCR and sequencing. These results were also
      observed for (60)Co gamma-rays irradiated human peripheral blood cells.
      CONCLUSION: Two novel mtDNA deletions, a 7455-bp deletion and a 9225-bp deletion,
      were induced by ionizing radiation. The rate of the mtDNA deletions within a
      normal population was related to the donors' age, but was independent of gender.

PMID- 23122311
TI  - Molecular typing of Leptospira interrogans strains isolated from Rattus tanezumi
      in Guizhou Province, Southwest of China.
AB  - OBJECTIVE: To identify and type three leptospires isolated from Rattus tanezumi
      in Guizhou Province by using three molecular techniques (PFGE, MLVA, and MLST),
      reveal the molecular characteristic of causative agents of local leptospirosis
      and evaluate these three molecular methods based on their detection resolution
      and efficiency. METHODS: Three Leptospira strains were isolated from the kidney
      of Rattus tanezumi and cultured with EMJH medium. PFGE, MLVA, and MLST assays
      were applied to type the three strains isolated from Rattus tanezumi in Guizhou
      Province. RESULTS: PFGE, MLVA, and MLST typing showed that the three leptospiral
      isolates matched with leptospiral serogroup Icterohaemorrhagiae serovar Lai. The
      findings of the genotyping methods were consistent. MLVA and MLST defined
      genotypes, whereas PFGE allowed the recognition of additional subgroups within
      the genotypes, and the findings of molecular typing were also consistent with
      those of traditional techniques. CONCLUSION: Three leptospiral isolates from
      Guizhou Province matched with leptospiral serogroup Icterohaemorrhagiae serovar
      Lai, and PFGE, MLVA, and MLST, as reliable molecular techniques for identifying
      and typing of Leptospira interrogans, would contribute to the active
      surveillance, outbreak investigation and source tracking for leptospirosis in
      Guizhou Province.

PMID- 23122312
TI  - Effects of benzo(a)pyrene on the contractile function of the thoracic aorta of
      Sprague-Dawley rats.
AB  - OBJECTIVE: To evaluate the possible vascular effects of an environment carcinogen
      benzo(a)pyrene (BaP). METHODS: The cytotoxicit of BaP and rat liver S9 (0.25
      mg/mL)-activated BaP were examined by MTT assay. Thoracic aortic rings were
      dissected from Sprague-Dawley rats. Contraction of aortic rings was induced by 60
      mmol/L KCl or 10(-6) mol/L phenylephrine (PE) in an ex-vivo perfusion system
      after BaP (100 MUmol/L) incubation for 6 h. [Ca(2+)](i) was measured using Fluo
      4/AM. For in-vivo treatment, rats were injected with BaP for 4 weeks (10 mg/kg,
      weekly, i.p.). RESULTS: BaP (1-500 MUm) did not significantly affect cell
      viability; S9-activated BaP stimulated cell proliferation. BaP did not affect the
      contractile function of endothelium-intact or -denuded aortic rings. BaP did not
      affect ATP-induced ([Ca(2+)](i)) increases in human umbilical vein endothelial
      cells. In BaP-treated rats, heart rate and the number of circulating inflammatory
      cells were not affected. Body weight decreased while blood pressure increased
      significantly. The maximum aortic contractile responses to PE and KCl and the
      maximum aortic relaxation response to acetylcholine were significantly decreased
      by 25.0%, 34.2%, and 10.4%, respectively. CONCLUSION: These results suggest, in
      accordance with its DNA-damaging properties, that metabolic activation is a
      prerequisite for BaP-induced cardiovascular toxicity.

PMID- 23122313
TI  - Study on female sexual dysfunction in type 2 diabetic Chinese women.
AB  - OBJECTIVE: To investigate the female sexual dysfunction (FSD) in type 2 diabetes
      patients, by comparing the sexual function between type 2 diabetic women and non
      diabetic women with Female Sexual Function Index (FSFI). METHODS: 115 type 2
      diabetic women and 107 age-matched non-diabetes women were enrolled with similar
      backgrounds. Their sexual functions were evaluated with FSFI. Metabolic
      parameters such as body mass index, blood lipid profile, hemoglobin A1C, plasma
      glucose were also collected. RESULTS: Total score of FSFI of the type 2 diabetic
      women were significantly lower than that of the non-diabetic controls (18.27+/
      8.96 vs. 23.02+/-5.78, P=0.000). Scores of the FSFI domains (desire, arousal,
      lubrication, orgasm, satisfaction, pain) of the type 2 diabetic group were also
      lower than those of the control group. According to the FSD criterion (FSFI<25)
      available in China, the percentage of FSD in the type 2 diabetic group was
      significantly higher than that of the control group (79.2%vs. 55.0%, P<0.001).
      These trends seemed more prominent in pre-menopause subgroups. The logistic
      regression analysis indicated that age and diabetes were independent risk factors
      of FSD. Body Mass Index (BMI) also had influence in the diabetes group.
      CONCLUSION: Findings from this study showed that there are more FDS in Chinese
      type 2 diabetic women than in their non-diabetic counterparts, especially in pre
      menopause participants.

PMID- 23122314
TI  - Clustering of inflammatory biomarkers and risk of hypertension in a Mongolian
      population in China.
AB  - OBJECTIVE: There is little knowledge on whether there is clustering of
      inflammatory biomarkers, such as C-reactive protein (CRP), soluble intracellular
      adhesion molecule1-1 (sICAM-1), and angiotensin II (Ang II), in individuals with
      hypertension in the Mongolian population. In the present study, we investigated
      this relationship in a Mongolian population in China. METHODS: A total of 2589
      adult Mongolians, aged 20 years and older, were recruited as study participants.
      Data on demographics, lifestyle, family history of hypertension, blood pressure,
      and blood chemistry were collected, and inflammatory biomarkers were measured in
      all participants. RESULTS: The proportion of subjects with increased levels of
      two or three biomarkers was significantly higher in those with hypertension
      (21.0% and 6.0%, respectively) than in those with prehypertension (12.7% and
      0.5%, respectively) or normotension (8.1% and 0.2%, respectively). The
      multivariate adjusted odds ratios (95% confidence interval) of hypertension
      associated with increased levels of one, two or three biomarkers were 0.94 (0.72
      1.22), 1.42 (0.93-2.16), and 11.08 (1.45-84.80), respectively, compared with
      subjects with no increase in any biomarker. CONCLUSION: Hypertension was
      associated with a cluster of inflammatory biomarkers in the Mongolian population.

PMID- 23122315
TI  - PSO/ACO algorithm-based risk assessment of human neural tube defects in Heshun
      County, China.
AB  - OBJECTIVE: To develop a new technique for assessing the risk of birth defects,
      which are a major cause of infant mortality and disability in many parts of the
      world. METHODS: The region of interest in this study was Heshun County, the
      county in China with the highest rate of neural tube defects (NTDs). A hybrid
      particle swarm optimization/ant colony optimization (PSO/ACO) algorithm was used
      to quantify the probability of NTDs occurring at villages with no births. The
      hybrid PSO/ACO algorithm is a form of artificial intelligence adapted for
      hierarchical classification. It is a powerful technique for modeling complex
      problems involving impacts of causes. RESULTS: The algorithm was easy to apply,
      with the accuracy of the results being 69.5%+/-7.02% at the 95% confidence level.
      CONCLUSION: The proposed method is simple to apply, has acceptable fault
      tolerance, and greatly enhances the accuracy of calculations.

PMID- 23122316
TI  - Comparison of concentrations of lead and cadmium in various parts of the femur
      head in patients after arthroplasty of the hip joint in Northwest Poland.
AB  - OBJECTIVE: To determine the concentrations of lead (Pb) and cadmium (Cd) in three
      kinds of materials (cartilage, cortical bone, and cancellous bone) of the femur
      head obtained from patients in the process of operation. METHODS: Concentrations
      of Pb and Cd were determined in selected parts of the femur head of 30 patients
      after total hip arthroplasty, using ICP-AES (atomic absorption
      spectrophotometry). RESULTS: Pb contained the highest concentration in cortical
      bone, while Cd did so in cancellous bone. There were statistically significant
      differences in the concentrations of both elements between the cartilage and
      cortical bone, and also differences in the concentration of Pb between the
      cartilage and cancellous bone. There were no significant differences in the
      concentrations of Pb or Cd between cortical and cancellous bone. CONCLUSION:
      Comparative studies on toxic metals should take into account both analogous bones
      and their fragments, as even if they come from the same kind of bones (e.g. femur
      head), clear differences exist in concentrations of heavy metals related to the
      sampling site and type of tissue (cartilage, cortical bone, and cancellous bone).

PMID- 23122317
TI  - Differential responses to UVB irradiation in human keratinocytes and epidermoid
      carcinoma cells.
AB  - OBJECTIVE: To examine UVB-induced responses in normal human keratinocytes (HaCaT)
      and epidermoid carcinoma cells (A431) at the cellular and molecular level, and
      investigated the protective effect of salidroside. METHODS: Cells irradiated by
      UVB at various dosage and their viability was assessed by MTT assays, cell cycle
      was analysed by flow cytometry. The expression of NF-kappaB, BCL-2, and CDK6
      after 50 J/m(2) UVB irradiation were detected by RT-PCR and western blotting.
      RESULTS: Our results confirmed greater tolerance of A341 cells to UVB-induced
      damage such as cell viability and cell cycle arrest, which was accompanied by
      differential expression changes in NF-kappaB, BCL-2, and CDK6. UVB exposure
      resulted in HaCaT cells undergoing G(1)-S phase arrest. When treated with
      salidroside, HaCaT survival was significantly enhanced following exposure to UVB,
      suggesting great therapeutic potential for this compound. CONCLUSION: Taken
      together, our study suggests that A431 respond differently to UVB than normal
      HaCaT cells, and supports a role for NF-kappaB, CDK6, and BCL-2 in UVB-induced
      cell G(1)-S phase arrest. Furthermore, salidroside can effectively protect HaCaT
      from UVB irradiation.

PMID- 23122318
TI  - Homology modeling of mosquitocidal Cry30Ca2 of Bacillus thuringiensis and its
      molecular docking with N-acetylgalactosamine.
AB  - OBJECTIVE: To investigate the theoretical model of the three-dimensional
      structure of mosquitocidal Cry30Ca2 and its molecular docking with N
      acetylgalactosamine. METHODS: The theoretical model of Cry30Ca2 was predicted by
      homology modeling on the structure of the Cry4Ba. Docking studies were performed
      to investigate the interaction of Cry30Ca2 with N-acetylgalactosamine on the
      putative receptor. RESULTS: Cry30Ca2 toxin is a rather compact molecule composed
      of three distinct domains and has approximate overall dimensions of 95 by 75 by
      60A. Domain II is a helix bundle, Domain II consists of three antiparallel beta
      sheets, Domain III is composed of two beta-sheets that adopt a beta-sandwich
      fold. Residue 321Ile in loop1, residues 342Gln 343Thr and 345Gln in loop2,
      residue 393Tyr in loop3 of Cry30Ca2 are responsible for the interactions with
      GalNAc via 7 hydrogen bonds, 6 of them were related to the oxygen atoms of
      hydroxyls of the ligand, and one to the nitrogen of the ligand. CONCLUSION: The
      3D structure of Cry30Ca2 resembles the previously reported Cry toxin structures
      but shows still some distinctions. Several residues in the loops of the apex of
      domain II are responsible for the interactions with N-acetylgalactosamine.

PMID- 23122319
TI  - Association between childhood leukaemia and exposure to power-frequency magnetic
      fields in Middle Europe.
AB  - OBJECTIVE: Higher levels of exposure to extremely low-frequency magnetic fields
      (ELF-MF) are associated with a slightly increased risk of childhood leukaemia.
      Compared with more-developed Western countries, higher exposure levels are
      evident in the Czech Republic, probably because of the different types of
      housing. In light of this, we aimed to examine the association between ELF-MF
      exposure and childhood leukaemia in the Czech Republic. METHODS: We conducted a
      paired case-control study. The cases (children with leukaemia) were age- sex- and
      permanent residence-matched to controls (children without leukaemia). Although
      this limited potential bias and confounding, it also limited our number of
      participants. RESULTS: The matched analyses included 79 case-control pairs. No
      significant association between ELF-MF exposure and childhood leukaemia was
      observed for exposures over 0.2 MUT (odds ratio [OR]=0.93, confidence interval
      [CI]=0.45-1.93), 0.3 MUT (OR=0.77, CI=0.34-1.75), or 0.4 MUT (OR=0.9, CI=0.37
      2.22). CONCLUSION: Despite higher levels of exposure in Middle and Eastern
      Europe, no indication of an association between ELF-MF exposure and childhood
      leukaemia was determined. This in contrast to the findings of previous studies
      conducted in different countries.

PMID- 23122320
TI  - Current status of canine rabies in China.
AB  - The number of human rabies cases acquired from dog bites constitutes a high
      proportion of the total rabies cases in China, although the number of human
      rabies cases has gradually decreased in recent years. The pivotal role of dogs in
      the spread of rabies indicates that controlling and preventing canine rabies
      could be a key step in eradicating human rabies in China. The primary aims of
      this review are to discuss the properties and pathogenesis of the rabies virus,
      the clinical signs and diagnosis of canine rabies, threshold host density and
      vaccination of dogs, and the prevention and control of canine rabies in China.

PMID- 23122321
TI  - Synthesis and characterization of new polyamides derived from alanine and valine
      derivatives.
AB  - BACKGROUND: Many efforts have been recently devoted to design, investigate and
      synthesize biocompatible, biodegradable polymers for applications in medicine for
      either the fabrication of biodegradable devices or as drug delivery systems. Many
      of them consist of condensation of polymers having incorporated peptide linkages
      susceptible to enzymatic cleavage. Polyamides (PAs) containing alpha-amino acid
      residues such as L-leucine, L-alanine and L-phenylalanine have been reported as
      biodegradable materials. Furthermore, polyamides (PAs) derived from C10 and C14
      dicarboxylic acids and amide-diamines derived from 1,6-hexanediamine or 1,12
      dodecanediamine and L-phenylalanine, L-valyl-L-phenylalanine or L-phenylalanyl-L
      valine residues have been reported as biocompatible polymers. We have previously
      described the synthesis and thermal properties of a new type of polyamides
      containing amino acids based on eight new symmetric meta-oriented protected
      diamines derived from coupling of amino acids namely; Fomc-glycine, Fmoc-alanine,
      Fomc-valine and Fomc-leucine with m-phenylene diamine or 2,6-diaminopyridine.
      Results revealed that incorporation of pyridine onto the polymeric backbone of
      all series decreases the thermal stability.Here we describe another family of
      polyamides based on benzene dicarboxylic acid, pyridine dicarboxylic acid, and
      alpha-amino acid linked to benzidine and 4,4'-oxydianiline to study the effect of
      the dicarboxylic acid as well as the amino acids on the nature and thermal
      stability of the polymers. RESULTS: We report here the preparation of a new type
      of polyamides based on benzene dicarboxylic acid, pyridine dicarboxylic acid, and
      alpha-amino acid linked to benzidine and 4,4'-oxydianiline to study the effect of
      the dicarboxylic acid as well as the amino acids on the nature and thermal
      stability of polymers. The thermal properties of the polymers were evaluated by
      different techniques. Results revealed that structure-thermal property
      correlation based on changing the dicarboxylic acid monomer or the diamine
      monomer demonstrated an interesting connection between a single change (changing
      the dicarboxylic acids in each series while the diamine is fixed) and thermal
      properties. The newly prepared polymers may possess biodegradability and thus may
      find some applications as novel biomaterials. CONCLUSIONS: The thermal properties
      of the new type of polyamides based on benzene dicarboxylic acid, pyridine
      dicarboxylic acid, and alpha-amino acid (alanine and valine) linked to benzidine
      and 4,4'-oxydianiline were evaluated by thermal gravimetric (TG), differential
      thermal gravimetric (DTG) and differential thermal analysis (DTA) techniques.
      Results revealed that the structure-thermal property correlation based on
      changing the dicarboxylic acid monomer or the diamine monomer demonstrated an
      interesting connection between a single change (changing the dicarboxylic acids
      in each series while the diamine is fixed) and thermal properties. In addition,
      pyridine-containing polymers exhibited semicrystalline characteristic with
      melting temperature, Tm. where none of the valine-containing polymers showed a
      melting and crystallization peak indicating that the polymers were amorphous.
      This is expected since L-valine side chain can inhibit close packing and
      eliminate crystallization. The newly prepared polymers may possess
      biodegradability and thus may find some applications as novel biomaterials.

PMID- 23122322
TI  - Neoadjuvant therapy in resectable pancreatic cancer: a critical review.
AB  - BACKGROUND: Pancreatic cancer is among the deadliest tumors. Due to intrinsic
      chemo- and radio-resistance, surgical resection remains the only chance for cure.
      However surgery alone is unable to considerably improve survival and
      complementary chemotherapy and radiotherapy in a multimodal approach have been
      tested. Adjuvant chemotherapy yielded a modest outcome improvement, whereas the
      use of adjuvant chemoradiation is highly controversial. In this scenario, the
      neoadjuvant approach has a strong theoretical rationale, but limited information
      on the efficacy of this strategy is available. MATERIALS AND METHODS: This review
      critically overviews the current knowledge, the rationale, the available data and
      information on neoadjuvant treatment in resectable pancreatic cancer. RESULTS:
      The very early systemic dissemination of pancreatic cancer endorses the rationale
      for an up-front use of systemic therapy. However, evidence collected so far
      depends on retrospective data, small case series that did not balance the
      different characteristics of patients suitable for surgery before or after
      neoadjuvant chemotherapy. CONCLUSION: Currently there is no straightforward
      evidence to support the routine clinical use of this strategy. Only a properly
      designed randomized trial testing combination chemotherapy regimens selected on
      the basis of their efficacy and activity against metastatic disease can address
      this issue.

PMID- 23122323
TI  - Can EEG characteristics predict development of epilepsy in autistic children?
AB  - BACKGROUND: The high occurrence of epilepsy in children with autism spectrum
      disorders (ASD) is a clear indication that ASD has a neurobiological basis. The
      current understanding of the association between epilepsy and ASD is still
      limited, but from a clinical point of view, this association should not be
      overlooked. AIMS: We investigated the electroencephalogram (EEG) paroxysmal
      abnormality in children with ASD and the incidence of later development of
      epilepsy. METHODS: Participants were recruited from University of Yamanashi
      hospital and 5 satellite hospitals between April 1, 2001 and March 31, 2005. EEG
      recordings and clinical evaluations were performed every 6 months for at least 6
      years, focusing on paroxysmal abnormality. We scored the occurrence and the
      location of spikes and evaluated the relation with later development of epilepsy.
      RESULTS: The prospective study included 21 patients with ASD (12 males and 9
      females) between the ages of 3 and 6 years. EEG paroxysmal abnormalities were
      present in 11/21 patients (52.4%). In addition, six of 21 patients (28.6%) had
      epilepsy at some point in their lives. The presence of frontal paroxysms was
      significantly associated with later development of epilepsy compared with
      centrotemporal paroxysmus (p < 0.003). The type of seizure diagnosed was mainly
      partial; in particular, partial with secondary generalization in 4/6 (66.7%).
      CONCLUSION: The presence of frontal paroxysms may indicate a higher risk of
      epilepsy in ASD.

PMID- 23122324
TI  - Molybdenum cofactor deficiency: review of 12 cases (MoCD and review).
AB  - Molybdenum cofactor deficiency is a rare inborn error of metabolism. The major
      clinical symptoms are intractable neonatal seizures, progressive encephalopathy,
      facial dysmorphic features and feeding difficulties. Most of the patients are
      misdiagnosed as hypoxic ischemic encephalopathy. The majority of patients have
      mutations in the MOCS1 and MOCS2 genes. Although the therapeutic treatment
      strategies have not been improved, genetic analysis is essential to elucidate the
      disease. Here, we report a review of 12 patients with Molybdenum cofactor
      deficiency reported from Turkey.

PMID- 23122325
TI  - Adjuvanted pandemic influenza vaccine: variation of emulsion components affects
      stability, antigen structure, and vaccine efficacy.
AB  - BACKGROUND: Adjuvant formulations are critical components of modern vaccines
      based on recombinant proteins, which are often poorly immunogenic without
      additional immune stimulants. Oil-in-water emulsions comprise an advanced class
      of vaccine adjuvants that are components of approved seasonal and pandemic
      influenza vaccines. However, few reports have been published that systematically
      evaluate the in vitro stability and in vivo adjuvant effects of different
      emulsion components. OBJECTIVES: To evaluate distinct classes of surfactants,
      oils, and excipients, for their effects on emulsion particle size stability,
      antigen structural interactions, and in vivo activity when formulated with a
      recombinant H5N1 antigen. METHODS: Emulsions were manufactured by high pressure
      homogenization and characterized alone or in the presence of vaccine antigen by
      dynamic light scattering, zeta potential, viscosity, pH, hemolytic activity,
      electron microscopy, fluorescence spectroscopy, and SDS-PAGE. In vivo vaccine
      activity in the murine model was characterized by measuring antibody titers,
      antibody-secreting plasma cells, hemagglutination inhibition titers, and cytokine
      production. RESULTS: We demonstrate that surfactant class and presence of
      additional excipients are not critical for biological activity, whereas oil
      structure is crucial. Moreover, we report that simplified two-component emulsions
      appear more stable by particle size than more complex formulations.Finally,
      differences in antigen structural interactions with the various emulsions do not
      appear to correlate with in vivo activity. CONCLUSIONS: Oil-in-water emulsions
      can significantly enhance antibody and cellular immune responses to a pandemic
      influenza antigen. The dramatic differences in adjuvant activity between squalene
      based emulsion and medium chain triglyceride-based emulsion are due principally
      to the biological activity of the oil composition rather than physical
      interactions of the antigen with the emulsion.

PMID- 23122326
TI  - Left atrial volume index and aortic stiffness index in adult hemodialysed
      patients--link between compliance and pressure mediated by endothelium
      dysfunction; a cross-sectional study.
AB  - BACKGROUND: This study was performed to investigate the relationship between
      elastic properties of aorta and left atrium volume index (LAVI) in hemodialyzed
      (HD) patients. METHODS: Study group was consisted of 73 patients (age 51,6 +/-
      7,6 years) treated by hemodialysis. In all patients standard echocardiography was
      performed. Aortic stiffness index (ASI) was calculated using formula: ASI = log
      (SBP/DBP)/[(Aomax-Aomin)/Aomin]. LAVI was calculated according to the formula:
      LAVI = [pi/6 x (LAmax x LAshort x LAlong)]/m(2). Additionally several indices
      were calculated: left ventricle mass (LVM), left ventricle mass index (LVMI),
      midwall fractional shortening (mFS), endsystolic stress (ESS), mFS/ESS.
      Additionally the laboratory parameters including lipidogram, troponin T (cTnT),
      NT-proBNP and asymmetric dimethylarginine (ADMA) were measured. RESULTS: The ASI
      was strong and significantly correlated with left atrium volume (LAV) and LAVI
      (respectively: 0,601; p < 0,001 and 0,598; p < 0,001). The ASI was independently
      and markedly associated with ADMA, cTnT, CRP, T-chol, and LDL-chol. The LAVI was
      independently and significantly correlated with NT-proBNP and cTnT. CONCLUSIONS:
      There is correlation between ASI and ADMA, marker of endothelium dysfunction.
      There is also association between LAVI and NT-proBNP, signs of elevated left
      atrium pressure. The strong correlation between ASI and LAVI, improved by
      associations of specific biochemical markers with these echocardiographic
      indices, suggests there is the link between elastic properties of aorta and left
      atrium pressure in hemodialysed patients mediated by endothelial dysfunction.

PMID- 23122327
TI  - Effects of experience and electronic stability control on low friction collision
      avoidance in a truck driving simulator.
AB  - Two experiments were carried out in a moving-base simulator, in which truck
      drivers of varying experience levels encountered a rear-end collision scenario on
      a low-friction road surface, with and without an electronic stability control
      (ESC) system. In the first experiment, the drivers experienced one instance of
      the rear-end scenario unexpectedly, and then several instances of a version of
      the scenario adapted for repeated collision avoidance. In the second experiment,
      the unexpected rear-end scenario concluded a stretch of driving otherwise
      unrelated to the study presented here. Across both experiments, novice drivers
      were found to collide more often than experienced drivers in the unexpected
      scenario. This result was found to be attributable mainly to longer steering
      reaction times of the novice drivers, possibly caused by lower expectancy for
      steering avoidance. The paradigm for repeated collision avoidance was able to
      reproduce the type of steering avoidance situation for which critical losses of
      control were observed in the unexpected scenario and, here, ESC was found to
      reliably reduce skidding and control loss. However, it remains unclear to what
      extent the results regarding ESC benefits in repeated avoidance are generalisable
      to unexpected situations. The approach of collecting data by appending one
      unexpected scenario to the end of an otherwise unrelated experiment was found
      useful, albeit with some caveats.

PMID- 23122328
TI  - The crash at Kerang: Investigating systemic and psychological factors leading to
      unintentional non-compliance at rail level crossings.
AB  - In 2007 a loaded semi-trailer truck struck a passenger train on a railway level
      crossing in Northern Victoria, Australia, killing eleven train passengers.
      Although the incident was formally investigated, why the truck driver proceeded
      through the crossing in the presence of a train remains unexplained. This article
      uses two juxtaposed Human Factors approaches to provide insight into the
      contributory factors underlying the incident. A systems analysis framework is
      used to examine the rail level crossing system in which the incident occurred and
      an individual psychological schema theory account is used to examine the failures
      which led the truck driver to proceed through the crossing in the presence of a
      train. The findings suggest that the primary cause of the incident was a looked
      but-failed-to-see error driven by a faulty activation of schema error, leading
      the truck driver to assume initially that the crossing was in fact in a non
      activated state with no train present. Moreover, various system-wide factors that
      shaped the rail level crossing 'system' and thus the incident are identified.

PMID- 23122330
TI  - Modulation of endogenous pathways enhances bioethanol yield and productivity in
      Escherichia coli.
AB  - BACKGROUND: E. coli is a robust host for various genetic manipulations and has
      been used commonly for bioconversion of hexose and pentose sugars into valuable
      products. One of the products that E. coli make under fermentative condition is
      ethanol. However, availability of limited reducing equivalence and generation of
      competing co-products undermine ethanol yield and productivity. Here, we have
      constructed an E. coli strain to produce high yield of ethanol from hexose and
      pentose sugars by modulating the expression of pyruvate dehydrogenase and acetate
      kinase and by deleting pathways for competing co-products. RESULTS: The
      availability of reducing equivalence in E. coli was increased by inducing the
      expression of the pyruvate dehydrogenase (PDH) operon under anaerobic condition
      after replacement of its promoter with the promoters of ldhA, frdA, pflB, adhE
      and gapA. The SSY05 strain, where PDH operon was expressed under gapA promoter,
      demonstrated highest PDH activity and maximum improvement in ethanol yield.
      Deletion of genes responsible for competing products, such as lactate (ldhA),
      succinate (frdA), acetate (ack) and formate (pflB), led to significant reduction
      in growth rate under anaerobic condition. Modulation of acetate kinase expression
      in SSY09 strain regained cell growth rate and ethanol was produced at the maximum
      rate of 12 mmol/l/h from glucose. The resultant SSY09(pZSack) strain efficiently
      fermented xylose under microaerobic condition and produced 25 g/l ethanol at the
      maximum rate of 6.84 mmol/l/h with 97% of the theoretical yield. More
      importantly, fermentation of mixture of glucose and xylose was achieved by
      SSY09(pZSack) strain under microaerobic condition and ethanol was produced at the
      maximum rate of 0.7 g/l/h (15 mmol/l/h), respectively, with greater than 85% of
      theoretical yield. CONCLUSIONS: The E. coli strain SSY09(pZSack) constructed via
      endogenous pathway engineering fermented glucose and xylose to ethanol with high
      yield and productivity. This strain lacking any foreign gene for ethanol
      fermentation is likely to be genetically more stable and therefore should be
      tested further for the fermentation of lignocellulosic hydrolysate at higher
      scale.

PMID- 23122331
TI  - NMR structure and dynamics of the C-terminal domain of R-type lectin from the
      earthworm Lumbricus terrestris.
AB  - The C-terminal domain (Ch; C-half) of the R-type earthworm 29-kDa lectin (EW29),
      isolated from the earthworm Lumbricus terrestris, has two sugar-binding sites, in
      subdomains alpha and gamma, and the protein uses the two sugar-binding sites for
      its function as a single domain-type haemagglutinin. Our previous NMR titration
      experiments showed that the alpha sugar-binding site is a high-affinity site and
      the gamma sugar-binding site is a low-affinity site. However, it remains unclear
      why the alpha sugar-binding site of EW29Ch binds to lactose much more strongly
      because the crystal structure of lactose-bound EW29Ch showed that the interaction
      between the alpha sugar-binding site and lactose was almost same as that between
      the gamma sugar-binding site and lactose. In the present study, we have
      determined the NMR structure of EW29Ch in the sugar-free state and performed
      (15)N relaxation experiments for EW29Ch in both the sugar-free state and the
      lactose-bound states. The conformation of EW29Ch in the sugar-free state was
      similar to that of EW29Ch in complex with lactose. Conformational changes upon
      binding of lactose were observed only for the alpha sugar-binding site. By
      contrast, the (15)N relaxation experiments revealed a conformational exchange at
      the alpha sugar-binding site in the sugar-free state, which was suppressed in the
      lactose-bound state. The conformational exchange phenomenon observed for the
      alpha sugar-binding site was not observed for the gamma sugar-binding site.
      Differences in the conformational change and the backbone dynamics between
      subdomains alpha and gamma may be associated with the difference of the sugar
      binding modes between the two sugar-binding sites. DATABASE: Structural data for
      the NMR structure of EW29Ch in the sugar-free state have been deposited in the
      Protein Data Bank database under accession number 2RST.

PMID- 23122332
TI  - Two electrocardiographic patterns in patients with sudden complete occlusion of
      the left main trunk without collateral circulation.

PMID- 23122333
TI  - Polymorphisms in dipeptidyl peptidase IV gene are associated with the risk of
      myocardial infarction in patients with atherosclerosis.
AB  - BACKGROUND: Dipeptidyl peptidase IV (DPP-IV) is not only important in pancreatic
      beta-cell regulation but also has proinflammatory actions that can contribute to
      atherosclerosis progression. Previously, we showed that DPP-IV is co-localized
      with CD31 (an endothelial cell marker) in the neovessels within the human
      atherosclerotic plaques. These characteristics of DPP-IV may predispose patients
      with coronary artery disease (CAD) to plaque rupture and thus to myocardial
      infarction. The goal of this investigation was to determine whether genetic
      alterations in DPP-IV predispose to plaque vulnerability and myocardial
      infarction (MI). METHODS: Between Aug 2004, and March 2007, blood samples of
      patients (age <60) with angiographically documented CAD were collected.
      Demographic, clinical, risk factor, and angiographic data were recorded. Eight
      hundred and seventy five patients of European ancestry with angiographic CAD were
      divided into those with MI (n=421) and those without (n=454). A genome-wide
      association study was performed using the Affymetrix 6.0 chip to identify loci
      that predispose to MI. In the current study we only focused on DPP4 gene to
      assess the association of single nucleotide polymorphisms (SNPs) in the DPP-IV
      gene and risk of MI in patients with CAD. For genotyped SNPs, association was
      tested by logistic regression with significance level of 0.05. Plasma DPP-IV
      level was measured using a commercial ELISA kit. RESULTS: Average patients' age
      at diagnosis of CAD was 46.8years for MI group and 50.8 in the non MI group.
      There was no difference in distribution of traditional risk factors between the
      two groups. We identified one SNP (rs3788979) that was significantly related to
      angiographic CAD with MI, vs. without MI (OR: 1.36, p=0.03). The association of
      the identified SNP to MI risk was not attenuated after adjustment for traditional
      risk factors. The SNP was associated with lower levels of plasma DPP-IV
      (p=0.005). Moreover, CAD patients with the major alleles (GG) and no MI had
      highest plasma DPP-IV levels. (481.6, p=0.002). CONCLUSIONS: A polymorphism in
      the DPP-IV gene in patients with known CAD may increase the risk of MI. This SNP
      is associated with decreased plasma DPP4 level in patients with MI.

PMID- 23122334
TI  - Titanocene / cyclodextrin supramolecular systems: a theoretical approach.
AB  - BACKGROUND: Recently, various metallocenes were synthesized and analyzed by
      biological activity point of view (such as antiproliferative properties):
      ruthenocenes, cobaltoceniums, titanocenes, zirconocenes, vanadocenes, niobocenes,
      molibdocenes etc. Two main disadvantages of metallocenes are the poor
      hydrosolubility and the hydrolytic instability. These problems could be resolved
      in two ways: synthetically modifying the structure or finding new formulations
      with enhanced properties. The aqueous solubility of metallocenes with cytostatic
      activities could be enhanced by molecular encapsulation in cyclodextrins, as well
      as the hydrolytic instability of these compounds could be reduced. RESULTS: This
      study presents a theoretical approach on the nanoencapsulation of a series of
      titanocenes with cytotoxic activity in alpha-, beta-, and gamma-cyclodextrin. The
      HyperChem 5.11 package was used for building and molecular modelling of
      titanocene and cyclodextrin structures, as well as for titanocene/cyclodextrin
      complex optimization. For titanocene/cyclodextrin complex optimization
      experiments, the titanocene and cyclodextrin structures in minimal energy
      conformations were set up at various distances and positions between molecules
      (molecular mechanics functionality, MM+). The best interaction between titanocene
      structures and cyclodextrins was obtained in the case of beta- and gamma
      cyclodextrin, having the hydrophobic moieties oriented to the secondary face of
      cyclodextrin. The hydrophobicity of titanocenes (logP) correlate with the
      titanocene-cyclodextrin interaction parameters, especially with the titanocene
      cyclodextrin interaction energy; the compatible geometry and the interaction
      energy denote that the titanocene/beta- and gamma-cyclodextrin complex can be
      achieved. Valuable quantitative structure-activity relationships (QSARs) were
      also obtained in the titanocene class by using the same logP as the main
      parameter for the in vitro cytotoxic activity against HeLa, K562, and Fem-x cell
      lines. CONCLUSIONS: According to our theoretical study, the
      titanocene/cyclodextrin inclusion compounds can be obtained (high interaction
      energy; the encapsulation is energetically favourable). Further, the most
      hydrophobic compounds are better encapsulated in beta- and gamma-cyclodextrin
      molecules and are more stable (from energetically point of view) in comparison
      with alpha-cyclodextrin case. This study suggests that the titanocene / beta- and
      gamma-cyclodextrin complexes (or synthetically modified cyclodextrins with higher
      water solubility) could be experimentally synthesized and could have enhanced
      cytotoxic activity and even lower toxicity.

PMID- 23122335
TI  - Expression pattern of genes encoding nitrate and ammonium assimilating enzymes in
      Arabidopsis thaliana exposed to short term NaCl stress.
AB  - Key steps in nitrate nutrition and assimilation were assessed over two weeks in
      control and 100mM NaCl-exposed Arabidopsis thaliana (Columbia) plants. The data
      showed that NaCl stress lowered nitrate contents in both leaves and roots. While
      NaCl stress decreased ammonium contents in leaves, it increased the contents in
      roots at the end of treatment. A survey of transcript levels of NIA1 (At1g77760)
      and NIA2 (At1g37130) and nitrate reductase (NR, EC 1.6.1.6) activity in the
      leaves and roots suggested a major role of NIA2 rather than NIA1 in the
      regulation of NR by salt stress. A drop in mRNA levels for GLN2 (At5g35630) and
      GLN1;2 (At1g66200) by salt was associated with a similar inhibition of glutamine
      synthetase (GS, EC 6.3.1.2) activity in the leaves. In the roots, NaCl stress was
      found to enhance mRNA levels of GLN2 and cytosolic-encoding genes (GLN1;1
      (At5g37600) and GLN1;2).

PMID- 23122336
TI  - A systematic view of rice heat shock transcription factor family using
      phylogenomic analysis.
AB  - The heat shock transcription factor (Hsf) family includes key regulators of the
      physiological response to heat stress. Here, we present a systematic analysis of
      the Hsf family in rice using a phylogenomics-based approach that integrates multi
      omics data into the context of a phylogenetic tree. For 25 previously identified
      Hsfs, we integrated anatomical meta-profiling data from 983 Affymetrix arrays
      into a phylogenetic tree, revealing a global view of the functional redundancy
      within this family. Interestingly, most of the Hsfs showed significant
      fluctuation in gene expression patterns, suggesting that they have condition- or
      stress-dependent roles. Therefore, we further analyzed the abiotic stress
      responses of the Hsfs using log(2-)fold change data in response to heat, cold,
      drought and salt stresses. Subsequently, we identified 19 Hsfs that are
      positively associated with heat stress, 11 with drought, 9 with salt, and 7 with
      cold stress, as indicated by at least a 2-fold change and coefficient of
      variation less than 1. The Hsf subfamily A2 was conserved in the heat stress
      response. The Hsf subfamily C showed a strong positive association with drought,
      salt and cold stresses. Downregulation of three members in the Hsf subfamily B in
      response to cold stress is characteristic. More interestingly, half of the Hsf
      subfamily B genes were upregulated by heat, drought and salt stresses, while one
      gene in the other half was downregulated by drought, salt, and cold stresses.
      Finally, we developed a hypothetical functional gene network mediated by
      OsHsfA2e/OsHsf-12 that is involved in thermotolerance as well as upregulated in
      response to heat. We expect that our data will help researchers design more
      efficient strategies to study the rice Hsf family with information about probable
      functional redundancy.

PMID- 23122337
TI  - Future trends?

PMID- 23122338
TI  - Government by the people, for the people.

PMID- 23122339
TI  - Painting collections in hospitals: humanity in medicine.

PMID- 23122340
TI  - Imaging advocacy in New Jersey: evolving expectations in the 21st century.

PMID- 23122341
TI  - Assessing PPACA's evolving impact on radiology.

PMID- 23122342
TI  - Doing it for the first time: Sex Sigma.

PMID- 23122343
TI  - ACR Appropriateness Criteria pretreatment staging of colorectal cancer.
AB  - Because virtually all patients with colonic cancer will undergo some form of
      surgical therapy, the role of preoperative imaging is directed at determining the
      presence or absence of synchronous carcinomas or adenomas and local or distant
      metastases. In contrast, preoperative staging for rectal carcinoma has
      significant therapeutic implications and will direct the use of radiation
      therapy, surgical excision, or chemotherapy. CT of the chest, abdomen, and pelvis
      is recommended for the initial evaluation for the preoperative assessment of
      patients with colorectal carcinoma. Although the overall accuracy of CT varies
      directly with the stage of colorectal carcinoma, CT can accurately assess the
      presence of metastatic disease. MRI using endorectal coils can accurately assess
      the depth of bowel wall penetration of rectal carcinomas. Phased-array coils
      provide additional information about lymph node involvement. Adding diffusion
      weighted imaging to conventional MRI yields better diagnostic accuracy than
      conventional MRI alone. Transrectal ultrasound can distinguish layers within the
      rectal wall and provides accurate assessment of the depth of tumor penetration
      and perirectal spread, and PET and PET/CT have been shown to alter therapy in
      almost one-third of patients with advanced primary rectal cancer. The ACR
      Appropriateness Criteria are evidence-based guidelines for specific clinical
      conditions that are reviewed every 2 years by a multidisciplinary expert panel.
      The guideline development and review include an extensive analysis of current
      medical literature from peer-reviewed journals and the application of a well
      established consensus methodology (modified Delphi) to rate the appropriateness
      of imaging and treatment procedures by the panel. In those instances in which
      evidence is lacking or not definitive, expert opinion may be used to recommend
      imaging or treatment.

PMID- 23122344
TI  - ACR white paper: New practice models--hospital employment of radiologists: a
      report from the ACR Future Trends Committee.
AB  - In response to the current era of rapid evolution of health care delivery and
      financing, radiologists are increasingly considering, as well as confronting, new
      practice models. Hospital employment is one such opportunity. Within this report
      to the ACR membership, the potential advantages and risks for radiologists
      considering hospital employment are examined.

PMID- 23122346
TI  - The recent downturn in utilization of CT: the start of a new trend?
AB  - PURPOSE: The aim of this study was to examine recent CT utilization trends to
      ascertain if growth is still occurring. METHODS: The nationwide Medicare Part B
      databases for 2000 through 2010 were used. All Current Procedural Terminology,
      fourth ed, codes for diagnostic CT (including CT angiography) were selected.
      Place-of-service codes were used to determine whether the studies were performed
      in inpatients, emergency department (ED) patients, hospital outpatient
      departments, or private offices. Utilization rates per 1,000 Medicare fee-for
      service beneficiaries were calculated. RESULTS: The total Medicare CT utilization
      rate increased each year from 325 per 1,000 in 2000 to 637 per 1,000 in 2009,
      representing a compound annual growth rate (CAGR) of 7.8%. But in 2010, the rate
      dropped for the first time, to 626 per 1,000 (-1.7%). For inpatient CT, the 2000
      to 2009 CAGR was +5.5%, followed by a drop of 4.5% in 2010. For hospital
      outpatient department CT, the 2000 to 2009 CAGR was +5.1%, followed by a drop of
      3.6% in 2010. For private office CT, the 2000 to 2009 CAGR was +11.3%, followed
      by a 7.8% drop in 2010. Emergency departments were the only location that saw
      continued growth, with a 2000 to 2009 CT CAGR of +15.2%, followed by another 8.4%
      increase in 2010. CONCLUSIONS: After years of rapid growth, CT use in the
      Medicare population declined by 1.7% in 2010. The proportional decline was even
      greater among inpatients, hospital outpatient departments, and offices. The only
      place of service for which growth continued was emergency departments. Without
      the effect of emergency departments, the decline in 2010 would have been 4.7%.
      This downturn should help alleviate previous concerns about overly rapid CT
      growth.

PMID- 23122345
TI  - Radiologist agreement for mammographic recall by case difficulty and finding
      type.
AB  - PURPOSE: The aim of this study was to assess agreement of mammographic
      interpretations by community radiologists with consensus interpretations of an
      expert radiology panel to inform approaches that improve mammographic
      performance. METHODS: From 6 mammographic registries, 119 community-based
      radiologists were recruited to assess 1 of 4 randomly assigned test sets of 109
      screening mammograms with comparison studies for no recall or recall, giving the
      most significant finding type (mass, calcifications, asymmetric density, or
      architectural distortion) and location. The mean proportion of agreement with an
      expert radiology panel was calculated by cancer status, finding type, and
      difficulty level of identifying the finding at the patient, breast, and lesion
      level. Concordance in finding type between study radiologists and the expert
      panel was also examined. For each finding type, the proportion of unnecessary
      recalls, defined as study radiologist recalls that were not expert panel recalls,
      was determined. RESULTS: Recall agreement was 100% for masses and for
      examinations with obvious findings in both cancer and noncancer cases. Among
      cancer cases, recall agreement was lower for lesions that were subtle (50%) or
      asymmetric (60%). Subtle noncancer findings and benign calcifications showed 33%
      agreement for recall. Agreement for finding responsible for recall was low,
      especially for architectural distortions (43%) and asymmetric densities (40%).
      Most unnecessary recalls (51%) were asymmetric densities. CONCLUSIONS: Agreement
      in mammographic interpretation was low for asymmetric densities and architectural
      distortions. Training focused on these interpretations could improve the accuracy
      of mammography and reduce unnecessary recalls.

PMID- 23122348
TI  - CT imaging: radiation risk reduction--real-life experience in a metropolitan
      outpatient imaging network.
AB  - The exponential growth of CT imaging has been fueled by recent technical
      advances, improved diagnostic accuracy, and medicolegal pressures. CT imaging has
      replaced many more invasive and expensive tests and has proven itself an
      indispensable part of diagnostic medicine. This growth in CT imaging, however,
      has also been accompanied by an unavoidable increased cumulative radiation
      exposure to the general public. It is important to fully understand the risks and
      benefits of and alternatives to CT imaging so that an informed decision can be
      made. A number of simple strategies may be used to minimize radiation exposure
      during CT imaging. These include protocol redesign and CT dose adjustments on the
      basis of each patient's body mass index, limiting length of coverage and
      multiphase examinations, and iterative reconstruction. At Imaging Healthcare
      Specialists, a highly successful program of radiation dose reduction was created,
      and dose savings of up to 90% have been achieved in select patients while
      maintaining diagnostic image quality. The approach is simple, reproducible, and
      inexpensive.

PMID- 23122347
TI  - Impact of socioeconomic status on ionizing radiation exposure from medical
      imaging in children.
AB  - PURPOSE: To characterize cumulative radiation exposure from diagnostic imaging
      (CEDI) in pediatric patients and to investigate its relationship to patients'
      socioeconomic status and comorbid medical conditions. METHODS: A retrospective
      cohort study of >19,000 pediatric patients seen within the outpatient clinic
      system of an academic tertiary care urban medical center during the month of
      January 2006 was conducted to estimate CEDI from all procedures performed within
      3 years of the index visit (until January 2009). Socioeconomic status was
      estimated from census tract geocoding. Comorbid medical conditions were
      identified from the electronic medical record. RESULTS: A total of 19,063
      patients underwent imaging tests within the index month. The mean age was 8.9 +/-
      6.3 years. Most had private insurance (56%), with 36% receiving Medicaid and 8%
      private payers. Our population lived in census tracts in which 27 +/- 16% of the
      population were below the federal poverty level with 62% living in areas in which
      20% of residents were living below the poverty level. There were differences in
      CEDI (P < .0001) by age, insurance type, and percentage poverty in the census
      tract of residence but not among racial groups (P = .6508). The association
      between poverty and CEDI was generally explained by the 26 Elixhauser diagnoses,
      with the exception of rheumatoid arthritis. CONCLUSION: Patients living in areas
      of greater poverty were exposed over time to more radiation from diagnostic
      testing than those living in areas with lower percentages of residents living in
      poverty. This association was explained almost entirely by the presence of
      disease burden. No direct association was found between socioeconomic status and
      CEDI.

PMID- 23122349
TI  - Experience with a practice quality improvement system in a university radiology
      department.
AB  - In 2007, the ABR established and implemented Maintenance of Certification as a
      way to ensure radiologists' licensure and competency and to promote lifelong
      learning. Maintenance of Certification was instated for all radiologists
      receiving diagnostic radiology certificates starting in 2002. The 4 components of
      Maintenance of Certification are (1) Evidence of Professional Standing, (2)
      Lifelong Learning and Self-Assessment, (3) Cognitive Expertise, and (4) Practice
      Quality Improvement (PQI). Creating a PQI program involves establishing basic
      goals that, when met, will best benefit a department's needs. Developing a PQI
      system that promotes quality improvement will benefit the individuals involved,
      the department, and the institution. Much good can come from these projects:
      improved patient safety, increased efficiency and throughput with resultant cost
      savings, improved outcomes, and revenue generation. In addition, these efforts
      ensure that faculty members and trainees understand the importance of quality
      efforts in daily practice. This article reflects the author's experience setting
      up a PQI program for the radiology department of a large urban teaching hospital.
      Six steps are suggested to guide the creation of an effective PQI program.

PMID- 23122350
TI  - ACGME 2011 duty-hour guidelines: consequences expected by radiology residency
      directors and chief residents.
AB  - PURPOSE: The aim of this study was to assess perceptions of the 2011 ACGME duty
      hour guidelines among radiology residency directors and chief residents with
      regard to resident training, the practice of radiology, the quality of resident
      life, and faculty and staff costs. METHODS: An online survey was sent to
      radiology program directors and chief residents via the Association of University
      Radiologists. RESULTS: The response rates were 36.7% for program directors and
      18.6% for chief residents. Responses were generally weakly negative from both
      radiology program directors and chief residents. CONCLUSIONS: Both radiology
      program directors and chief residents have negative perceptions of the effect of
      the 2011 ACGME duty-hour guidelines on radiology residency programs. There was
      significant disagreement between program directors and chief residents with
      regard to whether attending radiologists or residents would be more affected by
      the new guidelines.

PMID- 23122351
TI  - Resident and attending physician attitudes regarding an audience response system.
AB  - PURPOSE: Audience response system (ARS) technology is increasingly being
      incorporated into radiology education. The aim of this study was to gauge
      resident and attending physician attitudes regarding the use of an ARS in
      resident conferences. METHODS: An anonymous survey was sent to 38 residents and
      57 attending physicians to gauge their attitudes regarding the use of an ARS in
      resident lectures using a 5-point, Likert-type scale (1 = strongly disagree, 2 =
      disagree, 3 = neither agree nor disagree, 4 = agree, and 5 = strongly agree).
      RESULTS: A total of 30 of 38 residents (78.9%) and 26 of 57 attending
      radiologists (45.6%) responded. Residents viewed the incorporation of an ARS into
      lectures positively, replying that they learned better from lectures
      incorporating an ARS (mean, 4.03; 95% confidence interval [CI], 3.74-4.32), felt
      more comfortable answering questions using it (mean, 4.53; 95% CI, 4.25-4.81),
      and were more likely to attend a lecture that incorporated its use (mean, 3.70;
      95% CI, 3.37-4.03). The use of an ARS by attending physicians was limited (9 of
      26 [34.6%]), with respondents citing a lack of adequate training. Those attending
      physicians who used it viewed the system positively, stating that residents were
      more engaged when they used an ARS (mean, 4.33; 95% CI, 3.87-4.79). An ARS
      somewhat helped the faculty members gauge resident understanding of the lecture
      material (mean, 3.67; 95% CI, 2.95-4.40) and prepare future lectures (mean, 3.33;
      95% CI 2.68-3.98). CONCLUSIONS: Both residents and attending physicians favorably
      view audience response technology as a means to enhance education in didactic and
      case-based settings. Increased training on how to incorporate its use into
      teaching may drive additional utilization.

PMID- 23122352
TI  - Resident clinical duties while preparing for the ABR core examination: position
      statement of the Association of Program Directors in Radiology.
AB  - Historically, diagnostic radiology residents have been allowed time off from
      clinical duties to study for the ABR oral board examination. This practice has
      resulted in a disruptive "board frenzy" at many programs. The new ABR examination
      structure gives programs an opportunity to evaluate this practice. This position
      statement of the Association of Program Directors in Radiology describes the
      rationale behind a recommendation of no time off from clinical service before the
      ABR core examination.

PMID- 23122353
TI  - Variability of physics education in radiation oncology medical residency
      programs.
AB  - PURPOSE: The aim of this study was to compare the quality of medical physics
      education for radiation oncology medical residents. METHODS: An independent
      survey regarding physics education was carried out using e-mail. The survey
      contained 12 questions addressing the duration, length, and quality of education.
      Responses were tabulated and compared with the recommended educational scheme.
      RESULTS: Nearly 56% of institutions participated in this survey. Educational
      patterns were found to be significantly variable among institutions. Some have
      minimum physics education (10 lectures), and some have 90 lectures per year. In
      general, two-thirds of the institutions require residents to attend classes up to
      the third year. CONCLUSIONS: Significant variability of physics education for
      radiation oncology medical residents was observed, contrary to the national
      recommendations. With advanced treatment techniques, physics education should be
      given more importance, and the number of lectures should be increased to
      accommodate every aspect of radiation oncology practice.

PMID- 23122354
TI  - A collaborative capital planning process for departments of radiology.

PMID- 23122355
TI  - Radiation protection tools in interventional radiology.

PMID- 23122356
TI  - How can I be politically involved in radiology? A report of the Florida radiology
      Resident's Challenge.

PMID- 23122357
TI  - Malcolm Bagshaw.

PMID- 23122358
TI  - Re: "The general radiologist in the 21st century".

PMID- 23122360
TI  - Exploring the top of the protein folding funnel by experiment.
AB  - While there have been impressive advances in understanding protein folding over
      the past few decades, we are still far from the goal of solving the protein
      folding problem: predicting the folding pathway and final structure entirely from
      the amino acid sequence. One reason for this shortcoming may be the lack of
      understanding of the complexity of the unfolded state before folding and earliest
      steps in the process. Recent technological advances and applications of cutting
      edge techniques in novel ways have begun to reveal this complexity. Comparing the
      kinetics with recent molecular dynamics simulations on the microsecond timescale
      may lead to more detailed and predictive folding models.

PMID- 23122362
TI  - [Comments on peritonsillar infections: a prospective study of 100 consecutive
      cases].

PMID- 23122361
TI  - Candidiasis and other oral mucosal lesions during and after interferon therapy
      for HCV-related chronic liver diseases.
AB  - BACKGROUND: Oral lichen planus (OLP) is seen frequently in patients with
      hepatitis C virus (HCV) infection. The aim of this study was to evaluate the
      occurrence of oral candidiasis, other mucosal lesions, and xerostomia during
      interferon (IFN) therapy for HCV infection. METHODS: Of 124 patients with HCV
      infected liver diseases treated with IFN therapy in our hospital, 14 (mean age
      56.00 +/- 12.94 years) who attended to receive administration of IFN once a week
      were identified and examined for Candida infection and other oral lesions and for
      the measurement of salivary flow. Serological assays also were carried out.
      RESULTS: Cultures of Candida from the tongue surfaces were positive in 7 (50.0%)
      of the 14 patients with HCV infection at least once during IFN therapy. C.
      albicans was the most common species isolated. The incidence of Candida during
      treatment with IFN did not increase above that before treatment. Additional oral
      mucosal lesions were observed in 50.0% (7/14) of patients: OLP in three (21.4%),
      angular cheilitis in three (21.4%) and recurrent aphthous stomatitis in one
      (7.1%). OLP occurred in one patient before treatment with IFN, in one during
      treatment and in one at the end of treatment. 85.7% of the oral lesions were
      treated with topical steroids. We compared the characteristics of the 7 patients
      in whom Candida was detected at least once during IFN therapy (group 1) and the 7
      patients in whom Candida was not detected during IFN therapy (group 2). The
      prevalence of oral mucosal lesions (P=0.0075) and incidence of external use of
      steroids (P=0.0308) in group 1 were significantly higher than in group 2. The
      average body weight of group 1 decreased significantly compared to group 2
      (P=0.0088). Salivary flow decreased in all subjects throughout the course of IFN
      treatment and returned at 6th months after the end of treatment. In group 1, the
      level of albumin at the beginning of the 6th month of IFN administration was
      lower than in group 2 (P=0.0550). According to multivariate analysis, one factor,
      the presence of oral mucosal lesions, was associated with the detection of
      Candida. The adjusted odds ratio for the factor was 36.00 (95% confidence
      interval 2.68-1485.94). CONCLUSION: We should pay more attention to oral
      candidiasis as well as other oral mucosal lesions, in patients with weight loss
      during IFN treatment.

PMID- 23122363
TI  - Severe vestibulocochlear involvement in Wegener's granulomatosis: a rare
      presentation.

PMID- 23122364
TI  - [Laryngotracheal reconstruction with cryopreserved aortic allograft as a salvage
      technique when cricotracheal resection complications occur in paediatrics].

PMID- 23122365
TI  - Congenital disorders of glycosylation: first deaf patient treated with a cochlear
      implant.

PMID- 23122366
TI  - Intestinal-type sinonasal adenocarcinomas. Immunohistochemical profile of 66
      cases.
AB  - INTRODUCTION AND OBJECTIVES: Intestinal-type sinonasal adenocarcinomas are
      malignant epithelial tumours. Around 8-25% of all sinonasal malignant tumours are
      intestinal-type adenocarcinomas, which are related to wood dust exposure. Four
      histological subtypes have been described: papillary, colonic, solid and
      mucinous. We performed a pathological and immunohistochemical study in order to
      describe characteristics with prognostic, diagnostic and therapeutic value, and
      also to compare our results with previous studies. METHODS: Sixty six tumour
      samples were analysed and protein expression of p53, p16, E-cadherin, beta
      catenin, epidermal growth factor receptor (EGFR), human epidermal growth factor
      receptor 2 (HER2/neu) and cyclooxygenase-2 (COX-2) was performed by tissue
      microarray blocks. RESULTS: The 63% of cases were p53 positive; 37% showed
      nuclear staining with beta-catenin and 100% with E-cadherin, while 98% showed
      membrane staining with beta-catenin, 7% with EGFR, 8% with HER2/neu and 52% with
      COX-2; and 59% of the cases lost p16 expression. CONCLUSIONS: Intracranial
      invasion was the worst prognostic associated event. Solid and mucinous tumours
      were the most aggressive histological subtypes. Intracranial invasion was more
      frequent in mucinous subtype tumours. Immunohistochemical results were similar in
      all tumour subtypes, except for mucinous tumours, which showed weak expression of
      E-cadherin and beta-catenin. Comparing with previous studies, we found a lower
      expression of EGFR, HER2/neu and COX-2. The p16 expression was associated with
      worse survival and metastatic disease.

PMID- 23122367
TI  - Spectrum analysis in postural strategy on static tests in a healthy population.
AB  - INTRODUCTION AND OBJECTIVES: The power spectral density can be used to find a
      hidden behaviour in a physical system. We studied postural behaviour in a healthy
      population, by means of power spectral density, and compared it with a situation
      of complete immobility. METHODS: A group of healthy volunteers carried out the
      modified Clinical Test for Sensory Interaction in Balance. A fibre optic
      gyroscope device was used to record the data. We compared the power spectral
      density in these tests and with another recording where the device was
      motionless. We looked for significant differences using the ANOVA test. RESULTS:
      A power peak appeared at 8.4 Hz in all static tests. The static group showed
      significant differences with all the other tests. We found no statistically
      significant differences when visual input discriminated between 2 tests. There
      were statistically significant differences for the proprioceptive input.
      CONCLUSIONS: Brief movements are needed to maintain the quiet stance. The
      distinctive feature of these movements is a fundamental frequency at 1.4 Hz and a
      harmonic frequency at 8.4 Hz. Proprioceptive input is essential for balance.

PMID- 23122368
TI  - Hypocalcaemia after total thyroidectomy: incidence, control and treatment.
AB  - INTRODUCTION: Hypocalcaemia, although usually transitory, is the most frequent
      complication after total thyroidectomy. OBJECTIVE: To identify factors associated
      with a higher risk of hypoparathyroidism and related to aetiology and surgical
      procedure. MATERIALS AND METHODS: A total of 254 total thyroidectomies were
      analysed for the incidence of transitory or permanent hypocalcaemia based on the
      relationship with etiological and surgical factors. RESULTS: Transient
      hypocalcaemia was present in 29.1% of the cases and permanent hypocalcemia was
      present in 4.7%. Postoperative hypocalcaemia was lower in patients with
      completion thyroidectomy than in patients that underwent total thyroidectomy in a
      single operation, 12% vs. 31%. Patients with Graves-Basedow disease developed
      postoperative hypocalcaemia in 50% of the cases. Mean recovery time of
      parathyroid function was 5.2 months, with 72.2% of the patients recovering before
      6 months. CONCLUSIONS: Postoperative hypocalcaemia is a frequent complication of
      total thyroidectomy, but it is seldom permanent. Patients with Graves-Basedow
      disease have a higher incidence of postoperative hypocalcaemia and need closer
      follow-up. Postoperative calcium level analysis at 24 and 48 h after surgery is
      not useful for rapid identification of patients at high risk of hypocalcaemia.

PMID- 23122369
TI  - Unexpected cardiopulmonary arrest associated with influenza: our experience
      during the 2009 pandemic in Japan.

PMID- 23122370
TI  - [French Cochrane centre].

PMID- 23122371
TI  - [Presentation of the evidence-based medicine section].

PMID- 23122372
TI  - [An investigational study of acne treatment in France].
AB  - BACKGROUND: Acne is one of the main reasons for dermatological consultation.
      Management may seem standardized, in particular for mild to moderate juvenile
      facial acne, where topical treatments are used for mild cases and topical
      treatments associated with systemic antibiotics are used for moderate cases. The
      aim of this investigational study was to evaluate current treatment approaches
      for mild to moderate acne patients by French dermatologists in private practice.
      METHODS: During this study, more than 252 dermatologists practising in over 144
      French cities were asked about their preferred treatments (other than
      isotretinoin) for young acne patients. A questionnaire containing information
      about patient characteristics, disease severity and the prescribed therapy was
      completed by dermatologists at baseline and 2 months later. RESULTS: In total,
      3145 acne patients were analyzed. This study showed that in 53% of cases,
      dermatologists prescribed several topical treatments (up to three) associated
      with one or several systemic therapies (up to three), in addition to a cosmetic
      product. In 51% of cases, dermatologists prescribed only application of a
      dermatological cosmetic product for patients with very mild acne; in 41% of
      cases, a single treatment, especially a topical treatment, was prescribed for
      patients with mild acne, and in 59 and 64% of cases, two treatments (a
      combination of local and systemic therapy) were prescribed respectively for
      patients with moderate and severe acne. CONCLUSION: This study demonstrated the
      complexity of management of acne patients by dermatologists, particularly in the
      case of mild to severe acne. Most notably, such therapeutic complexity raises the
      question of compliance, a key factor in successful treatment.

PMID- 23122373
TI  - [Stevens-Johnson's syndrome following ingestion of gunpowder].
AB  - BACKGROUND: A cutaneous adverse drug reaction is a skin eruption secondary to the
      intake of a drug, be it prescribed by a medical practitioner or taken as auto
      medication for a given ailment. In this document we present an original case of
      Stevens-Johnson's syndrome secondary to the ingestion of gunpowder. PATIENTS AND
      METHODS: A 22-year-old female student was hospitalised for diffuse and painful
      skin eruptions for the previous three days. She had complained six days earlier
      of an allergic reaction to pineapples, an allergy she had presented for quite a
      long time. In an attempt to remedy the situation, her mother made her drink a
      solution made of gunpowder bought at a market mixed with some water. On the third
      day of this "treatment", the patient noticed eruptions on her skin. These were
      initially maculopapular, later becoming erosive, and she had a mild fever. Later,
      a variety of eruptions appeared on the skin, from hyper-pigmented macular papules
      to blisters and erosive lesions with no Nicolsky sign. These lesions spared the
      palms of the hands and the soles of the feet. The mucosa of the conjunctivae,
      nose, buccal cavity, vulva, vagina and anus were severely affected. This clinical
      presentation was typical of Steven Johnson syndrome. The patient had stopped
      taking the "treatment" when she noticed the first lesions. On therapy, the
      outcome was favourable, except for severe complications such as synechiae with
      diffuse dyschromia. CONCLUSION: To the best of our knowledge this is the first
      time gunpowder has been incriminated in Stevens-Johnson's syndrome.

PMID- 23122374
TI  - [Antidesmoglein antibodies in a patient with Hailey-Hailey disease].
AB  - BACKGROUND: Hailey-Hailey disease (HHD) is a rare hereditary disease in which the
      genetic defect is characterized by mutation in the ATP2C1 gene coding for a
      transmembrane calcium pump. It is generally considered a non-immunologic
      acantholytic dermatosis in which direct and indirect immunofluorescence studies
      are negative, unlike in autoimmune pemphigus. PATIENTS AND METHODS: We describe a
      case of HHD associated with antidesmoglein antibodies in a 53-year-old woman. The
      clinical symptoms and histology were typical of HHD. Antidesmoglein antibody
      tests were positive on several occasions and a difference was found between the
      two types of Elisa test performed (positive with the MBL kit, negative with the
      Euroimmun kit). DISCUSSION: The positive result for desmoglein antibodies could
      be due to unmasking of antigens by the mechanism of acantholysis. The specificity
      of the main desmoglein Elisa tests also requires discussion.

PMID- 23122375
TI  - [Acantholytic rosacea of the forehead and scalp in a patient with Hailey-Hailey
      disease].
AB  - BACKGROUND: Rosacea is a common dermatosis that can involve the bald area of the
      scalp. We report the case of a man presenting clinical symptoms of rosacea of the
      forehead and the scalp, but with a histological picture of familial chronic
      benign pemphigus. PATIENTS AND METHODS: A 47-year-old man with a history of
      Hailey-Hailey disease had been presenting facial dermatosis for 5 years. The
      clinical features were erythema with pustules and scales located on the mid
      forehead and the androgenic bald area of the frontal scalp. The histological
      aspect of the skin biopsy showed suprabasilar clefting and ancantholysis at all
      levels of the epidermis and sparse perivascular infiltrate. Direct
      immunofluorescence was negative. These findings were typical of Hailey-Hailey
      disease. Based on clinical findings, and without taking account of the skin
      biopsy results, treatment with doxycycline and a topical antifungal was
      administered for 3 months, leading to remission of symptoms. DISCUSSION: The site
      of rosacea on the bald area of the scalp in males is described in the literature,
      and when present, is probably enhanced by exposure to UV radiation. In this
      patient, the histological features were interpreted as histopathologically
      equivalent to Kobner phenomenon.

PMID- 23122376
TI  - [Guinea pigs and dermatophytosis].
AB  - BACKGROUND: The current trend of keeping "exotic" pets has led to the emergence
      of new types of fungal species that may be transmitted to humans [1]. We describe
      a form of dermatophytosis transmitted by a Guinea pig and caused by a new variety
      of dermatophyte. CASE REPORT: A 13-year-old girl developed multiple
      erythematosquamous and vesicular lesions with a highly inflammatory edge several
      weeks after acquiring a Guinea pig of apparently healthy appearance. Direct
      examination and culture tests demonstrated the presence of a dermatophyte closely
      related to the erinacei variant of Trichophyton mentagrophytes, from which it
      differed in terms of microscopic and macroscopic characteristics. The condition
      resolved on therapy with topical imidazole. DISCUSSION: This new type of
      dermatophyte has been identified in many patients coming into close contact with
      Guinea pigs in the region of Nancy. We would suggest the emergence of a novel
      variety of T. mentagrophytes, which has adapted to its new host following
      transmission to Guineas pigs from hedgehogs. We propose that it be named T.
      mentagrophytes var. porcellae.

PMID- 23122377
TI  - [Myeloproliferative hypereosinophilic syndrome revealed by bipolar mucosal
      ulcerations].
AB  - BACKGROUND: Hypereosinophilic syndrome (HES) is defined as an eosinophil count
      equal to or greater than 1.5 G/L for more than 6 months with organ damage (heart,
      nervous system, lung, etc) after the exclusion of other common causes of
      eosinophilia. A myeloproliferative variant of HES with FIP1L1-PDGFRalpha fusion
      gene inducing constitutive activation of a tyrosine kinase receptor has been
      characterized. We report a case in which the diagnosis was revealed by mucosal
      erosions and ulcerations. PATIENTS AND METHODS: A 50-year-old man reported
      bipolar erosions. He presented with an erosion on the glans, an ulceration on the
      lower lip and mild dermographism. He had an eosinophil count of 7.5 G/L (n<0.7)
      and raised LDH at 520 IU/L (n<480). Screening for the usual causes of
      eosinophilia was negative. Histology of the labial ulceration showed a
      polymorphous inflammatory infiltrate containing eosinophils. A chest scan
      demonstrated a ground glass-like pulmonary infiltrate and broncho-alveolar lavage
      revealed eosinophilic alveolitis. The myelogram showed rich bone marrow with
      eosinophils. FIP1L1-PDGFRalpha fusion transcript was detected in the blood.
      Imatinib (Glivec((r))) was initiated and a favourable outcome was achieved within
      a few months and maintained after one year of treatment. DISCUSSION: Cutaneous
      signs are frequent features of HES. They are polymorphous and include pruritis,
      erythematous rash and urticaria. Mucosal ulcerations are uncommon and appear more
      frequently with the myeloproliferative FIP1L1-PDGFRalpha-associated variant of
      HES. Early diagnosis allows the onset of a targeted treatment with imatinib that
      may prevent the apparition of organ damage.

PMID- 23122378
TI  - [Chronic lymphocytic leukaemia presenting with specific cutaneous infiltrates in
      the absence of lymphocytosis: Two cases].
AB  - BACKGROUND: Specific cutaneous infiltrates of chronic lymphocytic leukaemia (CLL)
      are rare. They occur after a mean disease duration of 3 years. CLL skin
      infiltrates as the primary manifestation of the disease have been reported, but a
      normal lymphocyte count at diagnosis is rare. We present two cases of CLL
      initially presenting in the skin, without lymphocytosis. PATIENTS AND METHODS: A
      53-year-old man developed papulonodular lesions of the face and infiltrated
      plaques of the scalp, and an 85-year-old woman presented erythematous nodules of
      the face and neck. Histopathology revealed a lymphocytic infiltrate, consisting
      of small mature B-cells CD20+, CD79+, with an aberrant phenotype CD5+. CD23 was
      positive in one case. The two patients had no lymphocytosis, but
      immunophenotyping was characteristic of CLL. In the second case, there was a sub
      mental adenopathy, histologic analysis of which was consistent with CLL. The CLL
      was classified as Binet stage A in the two cases. No disease progression was
      noted at follow-up. DISCUSSION: The unusual feature of these cases is the lack of
      lymphocytosis at diagnosis. Thus, the skin lesions resulted in further
      evaluations for CLL, although the diagnosis was not suggested by the blood count.
      CONCLUSION: Skin involvement in CLL does not appear to be a poor prognostic
      indicator, arguing in favour of recruitment of circulating monoclonal B-cells
      rather than an additional tumour mass.

PMID- 23122379
TI  - [Congenital syringocystadenoma papilliferum].

PMID- 23122380
TI  - [Body-weight changes in psoriatic patients on systemic treatment].

PMID- 23122381
TI  - [Dermatoscopy of hair and scalp].

PMID- 23122382
TI  - [Porokeratosis].

PMID- 23122383
TI  - [Blue naevi and variants].

PMID- 23122384
TI  - [Chondroid syringoma of the face].

PMID- 23122385
TI  - [An outbreak of eruptive pseudoangiomatosis].

PMID- 23122386
TI  - [Naturism and skin throughout history (18th century to mid 20th century)].

PMID- 23122387
TI  - [MAP-Kinase pathway abnormalities in melanoma: B-RAF is not the sole cause].

PMID- 23122388
TI  - [New hope in metastatic melanoma treatment?].

PMID- 23122389
TI  - [Cutaneous pseudolymphoma with two types of anti-TNFalpha: a class effect?].

PMID- 23122390
TI  - Relative host body condition and food availability influence epidemic dynamics: a
      Poecilia reticulata-Gyrodactylus turnbulli host-parasite model.
AB  - Understanding disease transmission is important to species management and human
      health. Host body condition, nutrition and disease susceptibility interact in a
      complex manner, and while the individual effects of these variables are well
      known, our understanding of how they interact and translate to population
      dynamics is limited. Our objective was to determine whether host relative body
      condition influences epidemic dynamics, and how this relationship is affected by
      food availability. Poecilia reticulata (guppies) of roughly similar size were
      selected and assembled randomly into populations of 10 guppies assigned to 3
      different food availability treatments, and the relative condition index (Kn) of
      each fish was calculated. We infected 1 individual per group ('source' fish) with
      Gyrodactyus turnbulli and counted parasites on each fish every other day for 10
      days. Epidemic parameters for each population were analysed using generalized
      linear models. High host Kn-particularly that of the 'source' fish-exerted a
      positive effect on incidence, peak parasite burden, and the degree of parasite
      aggregation. Low food availability increased the strength of the associations
      with peak burden and aggregation. Our findings suggest that host Kn and food
      availability interact to influence epidemic dynamics, and that the condition of
      the individual that brings the parasite into the host population has a profound
      impact on the spread of infection.

PMID- 23122391
TI  - Fuzzy method for pre-diagnosis of breast cancer from the Fine Needle Aspirate
      analysis.
AB  - BACKGROUND: Across the globe, breast cancer is one of the leading causes of death
      among women and, currently, Fine Needle Aspirate (FNA) with visual interpretation
      is the easiest and fastest biopsy technique for the diagnosis of this deadly
      disease. Unfortunately, the ability of this method to diagnose cancer correctly
      when the disease is present varies greatly, from 65% to 98%. This article
      introduces a method to assist in the diagnosis and second opinion of breast
      cancer from the analysis of descriptors extracted from smears of breast mass
      obtained by FNA, with the use of computational intelligence resources--in this
      case, fuzzy logic. METHODS: For data acquisition of FNA, the Wisconsin Diagnostic
      Breast Cancer Data (WDBC), from the University of California at Irvine (UCI)
      Machine Learning Repository, available on the internet through the UCI domain was
      used. The knowledge acquisition process was carried out by the extraction and
      analysis of numerical data of the WDBC and by interviews and discussions with
      medical experts. The PDM-FNA-Fuzzy was developed in four steps: 1) Fuzzification
      Stage; 2) Rules Base; 3) Inference Stage; and 4) Defuzzification Stage.
      Performance cross-validation was used in the tests, with three databases with
      gold pattern clinical cases randomly extracted from the WDBC. The final
      validation was held by medical specialists in pathology, mastology and general
      practice, and with gold pattern clinical cases, i.e. with known and clinically
      confirmed diagnosis. RESULTS: The Fuzzy Method developed provides breast cancer
      pre-diagnosis with 98.59% sensitivity (correct pre-diagnosis of malignancies);
      and 85.43% specificity (correct pre-diagnosis of benign cases). Due to the high
      sensitivity presented, these results are considered satisfactory, both by the
      opinion of medical specialists in the aforementioned areas and by comparison with
      other studies involving breast cancer diagnosis using FNA. CONCLUSIONS: This
      paper presents an intelligent method to assist in the diagnosis and second
      opinion of breast cancer, using a fuzzy method capable of processing and sorting
      data extracted from smears of breast mass obtained by FNA, with satisfactory
      levels of sensitivity and specificity. The main contribution of the proposed
      method is the reduction of the variation hit of malignant cases when compared to
      visual interpretation currently applied in the diagnosis by FNA. While the MPD
      FNA-Fuzzy features stable sensitivity at 98.59%, visual interpretation diagnosis
      provides a sensitivity variation from 65% to 98% (this track showing sensitivity
      levels below those considered satisfactory by medical specialists). Note that
      this method will be used in an Intelligent Virtual Environment to assist the
      decision-making (IVEMI), which amplifies its contribution.

PMID- 23122392
TI  - Cardiac myxoma induced paraneoplastic syndromes: a review of the literature.
AB  - BACKGROUND: Atrial myxomas are the most common benign tumors of the heart and may
      present with a wide variety of symptoms. Although 45% of patients present with
      neurological symptoms, a diverse range of systemic symptoms also occur. METHODS:
      A systemic review of the literature related to the diagnosis, treatment,
      pathogenesis, and symptoms associated with atrial myxomas was performed. RESULTS:
      Here we summarize the current state of understanding about myxoma pathogenesis
      and treatments are described. We review the common and rare local and systemic
      effects of myxomas. Additionally, we review the paraneoplastic and metastatic
      potential of myxomas. CONCLUSIONS: A better understanding of the diverse disease
      presentations, paraneoplastic syndromes, and side effects of cytokine
      abnormalities stemming from myxomas will aid the physician in earlier detection
      and monitoring of disease recurrence.

PMID- 23122393
TI  - Inclusion into a heart failure critical pathway reduces the risk of death or
      readmission after hospital discharge.
AB  - BACKGROUND: Evidence-based therapies can lower the risk of death or hospital
      admission in heart failure (HF) patients, but are underprescribed. Critical
      pathways are one means of supporting systematic use of evidence-based
      recommendations. METHODS: Patients admitted for HF in one hospital in 2009 and
      included in a critical pathway were compared with a control group of patients
      admitted in 2007. The primary endpoint was the risk of death or readmission
      within 90 days after discharge. The hazard ratio of death or readmission was
      evaluated in a multivariate Cox proportional hazard model adjusting for age, sex,
      co-morbidities, and length of stay. RESULTS: Three hundred and sixty-three
      patients were evaluated (151 in the critical pathway and 212 in the control
      group). Adjusted hazard ratio for death or readmission at 90 days was 0.72 (95 CI
      0.51-1.00, p=0.049). Adhesion to guidelines was significantly better for patients
      included in the critical pathway (p=0.004), with more frequent prescription of
      beta-blockers (70.9% (95% CI 62.9-78.0) vs. 56.6% (95% CI 49.6-63.4), p=0.006),
      and evaluation of left ventricular ejection fraction (LVEF, 73.5% (95% CI 65.7
      80.3) vs. 57.5% (95% CI 50.6-64.3), p=0.002). Patients with reduced LVEF seem to
      have benefited the most from the inclusion in the critical pathway. CONCLUSIONS:
      Implementation of a critical pathway for patients hospitalized for HF was
      associated with a 28% reduction of the relative risk of death or readmission and
      improved adhesion to guidelines.

PMID- 23122394
TI  - Characterization and identification of alanine to serine sequence variants in an
      IgG4 monoclonal antibody produced in mammalian cell lines.
AB  - Low levels of alanine to serine sequence variants were identified in an IgG4
      monoclonal antibody by ultra/high performance liquid chromatography and tandem
      mass spectrometry. The levels of the identified sequence variants A183S and
      A152S, both in the light chain, have been determined to be 7.8-9.9% and 0.5-0.6%,
      by extracted ion currents of the tryptic peptides L16 and L14, respectively. The
      A183S variant was confirmed through tryptic map spiking experiments using
      synthetic peptide, SDYEK, which incorporated Ser at the position of native Ala in
      the tryptic peptide L16. Both mutations were also observed by endoproteinase Asp
      N peptide mapping. The variant level of A183S was also quantified by LC-UV with
      detection at 280nm and fluorescence detection of tyrosine residues on the tryptic
      peptides. The results from LC-MS, UV, and fluorescence detection are in close
      agreement with each other. The levels of the sequence variants are comparable
      among the antibody samples manufactured at different scales as well as locations,
      indicating that the variants' levels are not affected by manufacture scale or
      locations. DNA sequencing of the master cell bank revealed the presence of mixed
      bases at position 183 encoding both wild and mutated populations, whereas bases
      encoding the minor sequence variant at position 152 were not detected. The root
      cause for A152S mutation is not yet clearly understood at this moment.

PMID- 23122395
TI  - Short-incubation mass spectrometry assay for lysosomal storage disorders in
      newborn and high-risk population screening.
AB  - The interest in early detection strategies for lysosomal storage disorders (LSDs)
      in newborns and high-risk population has increased in the last years due to the
      availability of novel treatment strategies coupled with the development of
      diagnostic techniques. We report the development of a short-incubation mass
      spectrometry-based protocol that allows the detection of Gaucher, Niemann-Pick
      A/B, Pompe, Fabry and mucopolysaccharidosis type I disease within 4h including
      sample preparation from dried blood spots. Optimized sample handling without the
      need of time-consuming offline preparations, such as liquid-liquid and solid
      phase extraction, allows the simultaneous quantification of five lysosomal enzyme
      activities using a cassette of substrates and deuterated internal standards.
      Applying incubation times of 3h revealed in intra-day CV% values ranging from 4%
      to 11% for all five enzyme activities, respectively. In a first clinical
      evaluation, we tested 825 unaffected newborns and 16 patients with LSDs using a
      multiplexed, turbulent flow chromatography-ultra high performance liquid
      chromatography-tandem mass spectrometer assay. All affected patients were
      identified accurately and could be differentiated from non-affected newborns. In
      comparison to previously published two-day assays, which included an overnight
      incubation, this protocol enabled the detection of lysosomal enzyme activities
      from sample to first result within half a day.

PMID- 23122396
TI  - Sensitive determination of the peptide AP301--a motif of TNF-alpha--from human
      plasma using HPLC-MS/MS.
AB  - The AP301 peptide mimics the lectin-like domain of TNF-alpha. The synthetic
      peptide AP301 (molecular weight 1923.1amu) is composed of 17 amino acids and
      contains an intramolecular disulfide bond between the N-terminal and the C
      terminal cysteine. AP301 interacts with the endothelial sodium channel (ENaC) and
      activates pulmonary liquid clearance both in vitro and in animal studies.
      Currently, AP301 is subject to clinical investigations for the treatment of
      pulmonary oedema. With HPLC-MS/MS on reversed phase chromatography a
      determination limit of 1ng AP301/mL human plasma can be achieved. The MS
      ionisation was done with ESI positive. 50MUL of human plasma was mixed with the
      internal standard (a stable isotope labelled AP301, with a total of 6 carbon 13)
      in acetonitrile for protein precipitation. After centrifugation a part of the
      clear supernatant was injected into HPLC-MS/MS. Validation was performed
      according to FDA-guideline in three batches [U.S. Department of Health and Human
      Services, Food and Drug Administration (FDA): Guidance for Industry,
      Bioanalytical Method Validation, May 2001]. By using a 6xC13 isotopically
      labelled internal standard good precision, accuracy and linearity can be gained.
      The inter-batch precision (CV) of the quality control samples in human plasma
      (conc. 2.50/20/240ng/mL) ranged from 5.54 to 10.15%. The inter-batch accuracy
      (with reference to the mean value) of the quality control samples in plasma
      ranged from 96.1% to 99.9%. The analyte was stable in human plasma over three
      freeze/thaw cycles, or for 4h at room temperature, or for at least 20weeks when
      stored at below -20 degrees C. This method was used for quantifying AP301 after
      inhalative application in a phase I-study.

PMID- 23122397
TI  - Analysis of coenzyme Q(10) in lymphocytes by HPLC-MS/MS.
AB  - Coenzyme Q(10) (CoQ(10)) deficiency syndromes are potentially treatable
      disorders. Skeletal muscle is the most widely accepted tissue for their study,
      but sampling is an invasive procedure. Cultured skin fibroblasts seem to improve
      the biochemical diagnosis, but their growth requires a certain period of time.
      Our aim was to set up a minimally invasive, fast and reliable analytical
      procedure to measure CoQ(10) in lymphocytes, to prevent any delay in diagnosing
      primary CoQ(10) deficiency. HPLC-MS/MS analysis of CoQ(10) showed high
      sensitivity and specificity. The reference range was established in apparently
      healthy volunteers (n=33); the mean of CoQ(10) in lymphocytes was 107nmol/g
      protein (95% confidence interval: 105-120) and 2.0nmol/UCS (95% confidence
      interval: 2.06-2.46). Therefore, the range was narrower when normalized to units
      of citrate synthase (UCS) than when normalized to grams of protein. The method
      was linear from 0.01 to 1MUM with a good precision and sensitivity (limit of
      quantification 0.01MUM). Intra-assay and inter-assay coefficients of variation
      were lower than 13%. Recovery was higher than 95%. In our hands, lymphocytes seem
      to be a reliable matrix as they reflect intracellular content of CoQ(10). In
      addition, they can be obtained by a minimally invasive procedure (venipuncture).

PMID- 23122398
TI  - Trace determination of beta-blockers and beta2-agonists in distilled and waste
      waters using liquid chromatography-tandem mass spectrometry and solid-phase
      extraction.
AB  - A highly sensitive method for simultaneous determinations of eleven beta-blockers
      and beta-agonists in distilled and waste-waters using liquid chromatography
      electrospray ionization-tandem mass spectrometry (LC-ESI-MS-MS) was developed,
      optimized and validated. The method was used for trace determinations of
      acebutolol, atenolol, metoprolol, propranolol, timolol, nadolol, labetalol,
      oxprenolol, pindolol, alprenolol and terbutaline. Oasis MCX and Clean Screen
      cartridges were used for solid phase extractions and an alkaline mixture of
      dichloromethane-propanol was used as mobile phase. Matrix effect was reduced by
      using methanol as a pre-eluant for removing co-extractives on the SPE cartridges
      and by applying the internal standard method for quantification. Using Oasis MCX
      SPE cartridges, developed method gave average recoveries of 77.20-97.30% for
      drugs spiked at 150.00-500.00pg/ml. Intra-day precisions gave RSD of 3.367
      12.489% while as inter-day precisions gave RSD of 6.425-19.768%. Detection limits
      of 0.11-6.74pg/ml and quantification limits of 0.14-22.88pg/ml were obtained.
      Signal's suppression in the range of 4.50-24.50% was recorded due to the matrix
      effect. Drugs spiked in wastewater at 500.00pg/ml concentrations level and stored
      at 4 degrees C for 6 days, showed insignificant degradation. Developed method was
      successfully applied to the analysis of pharmaceutical residues in effluents
      wastewaters. Five beta-blockers and one beta-agonists were detected in Al-Ain and
      Abu Dhabi wastewaters at average concentrations of 3.44-19.05pg/ml. Atenolol was
      detected at higher average concentration ranged in 125.60-234.28pg/ml. Results
      obtained suggest that adopted wastewater treatment processes are not enough to
      degrade these compounds.

PMID- 23122399
TI  - Pharmacokinetics of protocatechuic acid in mouse and its quantification in human
      plasma using LC-tandem mass spectrometry.
AB  - Protocatechuic acid (PCA), a major microbial-mediated metabolite of anthocyanins,
      has significant anti-oxidative and anti-carcinogenic activities in vitro and in
      vivo; however, its pharmacokinetics remains largely unknown. In this report, a
      sensitive and rapid LC-MS/MS method was developed and validated for the
      measurement of PCA concentrations in both mouse and human plasma. This method
      showed a linearity of 1-1000ng/mL in both mouse and human plasma with a lower
      limit of quantification of 1ng/mL. The within-day and between-day coefficient of
      variation ranged from 1.18 to 11.8% and accuracy from 92 to 110%. The method was
      applied to characterize the pharmacokinetics of PCA in mice after oral
      administration of 50mg/kg PCA. PCA was absorbed rapidly with a half-life of
      2.9min, reached a peak plasma level (C(max)) of 73.6MUM at 5min, and remained
      detectable up to 8h with the initial elimination half-life of about 3min and a
      terminal half-life of 16min. The area under the plasma concentration-time curve
      (AUC(0->8h)) of PCA was 1456MUMmin. The method was capable of detecting low ng/mL
      quantities of PCA in the plasma of patients with prostate cancer after an oral
      ingestion of 60g of black raspberry (BRB) powder. Because PCA is derived from the
      anthocyanins in BRB, our method provides a useful analytical tool to further
      investigate the metabolism of anthocyanins, and the pharmacology of PCA in future
      pre-clinical and clinical studies.

PMID- 23122400
TI  - Dynamic affinity chromatography in the separation of sulfated lignins binding to
      thrombin.
AB  - Sulfated low molecular weight lignins (LMWLs), a mixture of chemo-enzymatically
      prepared oligomers, have been found to be potent antagonists of coagulation.
      However, structures that induce anticoagulation remain unidentified. The highly
      polar sulfate groups on these molecules and the thousands of different structures
      present in these mixtures make traditional chromatographic resolution of sulfated
      LMWLs difficult. We performed dynamic thrombin affinity chromatography monitored
      using chromogenic substrate hydrolysis assay to isolate sulfated LMWL fractions
      that differed significantly in their biophysical and biochemical properties.
      Three fractions, I(35), I(55) and Peak II, were isolated from the starting
      complex mixture. Independent plasma clotting assays suggested that I(35)
      possessed good anticoagulation potential (APTT=4.2MUM; PT=6.8MUM), while I(55)
      and Peak II were approximately 10- and 100-fold less potent. The ESI-MS spectrum
      of this oligomeric fraction showed multiple peaks at 684.8, 610.6, 557.4, 541.4,
      536.5, and 519.4m/z, which most probably arise from variably functionalized beta
      O4beta-beta-linked trimers and/or a beta-O4beta-O4-linked dimers. The first
      direct observation of these structures in sulfated LMWLs will greatly assist in
      the discovery of more potent sulfated LMWL-based anticoagulants.

PMID- 23122401
TI  - Simultaneous determination of morinidazole, its N-oxide, sulfate, and
      diastereoisomeric N(+)-glucuronides in human plasma by liquid chromatography
      tandem mass spectrometry.
AB  - Morinidazole is a new third-generation 5-nitroimidazole antimicrobial drug. To
      investigate the pharmacokinetic profiles of morinidazole and its major
      metabolites in humans, a liquid chromatography-tandem mass spectrometry method
      was developed and validated for simultaneous determination of morinidazole, its N
      oxide metabolite (M4-1), a sulfate conjugate (M7), and two diastereoisomeric N(+)
      glucuronides (M8-1 and M8-2) in human plasma. A simple acetonitrile-induced
      protein precipitation was employed to extract five analytes and internal standard
      metronidazole from 50MUL human plasma. To avoid the interference from the in
      source dissociation of the sulfate and achieve the baseline-separation of
      diastereoisomeric N(+)-glucuronides, all the analytes were separated from each
      other with the mobile phase consisting of 10mM ammonium formate and acetonitrile
      using gradient elution on a Hydro-RP C(18) column (50mm*2mm, 4MUm) with a total
      run time of 5min. The API 4000 triple quadrupole mass spectrometer was operated
      under the multiple reaction-monitoring mode using the electrospray ionization
      technique. The developed method was linear in the concentration ranges of 10.0
      12,000ng/mL for morinidazole, 1.00-200ng/mL for M4-1, 2.50-500ng/mL for M7, 3.00
      600ng/mL for M8-1, and 10.0-3000ng/mL for M8-2. The intra- and inter-day
      precisions for each analyte met the accepted value. Results of the stability of
      morinidazole and its metabolites in human plasma were also presented. The method
      was successfully applied to the clinical pharmacokinetic studies of morinidazole
      injection in healthy subjects, patients with moderate hepatic insufficiency, and
      patients with severe renal insufficiency, respectively.

PMID- 23122402
TI  - Chromatographic behaviour of peptides following dimethylation with H2/D2
      formaldehyde: implications for comparative proteomics.
AB  - The differential separation of deuterated and non-deuterated forms of
      isotopically substituted compounds in chromatography is a well-known but not well
      understood phenomenon. This separation is relevant in comparative proteomics,
      where stable isotopes are used for differential labelling and the effect of
      isotope resolution on quantitation has been used to disqualify some deuterium
      labelling methods in favour of heavier isotopes. In this work, a detailed
      evaluation of the extent of isotopic separation and its impact on quantitation
      was performed for peptides labelled through dimethylation with H(2)/D(2)
      formaldehyde. The chromatographic behaviour of 71 labelled peptide pairs from
      quadruplicate tryptic digests of bovine serum albumin were analysed, focusing on
      differences in median retention times, resolution, and relative quantitation for
      each peptide. For 94% of peptides, the retention time difference (heavy-light)
      was less than 12s with a median value 3.4s. With the exception of a single
      anomalous pair, isotope resolution was below 0.6 with a median value 0.11.
      Quantitative assessment indicates that the bias in ratio calculation introduced
      by retention time shifts is only about 3%, substantially smaller than the
      variation in ratio measurements themselves. Computational studies on the dipole
      moments of deuterated labels indicate that these results are consistent with
      literature suggestions that retention time shifts are inversely related to the
      polarity of the label. This study suggests that the incorporation of deuterium
      isotopes through peptide dimethylation at amine residues is a viable route to
      proteome quantitation.

PMID- 23122403
TI  - Determination of non-steroidal anti-inflammatory drugs in urine by hollow-fiber
      liquid membrane-protected solid-phase microextraction based on sol-gel fiber
      coating.
AB  - A new rapid, simple and effective cleanup procedure is demonstrated for the
      determination of ibuprofen, naproxen and diclofenac in urine samples by using
      hollow-fiber liquid membrane-protected solid-phase microextraction (HFLM-SPME)
      based on sol-gel technique and gas chromatography-flame ionization detector (GC
      FID). In this technique, a sol-gel coated fiber was protected with a length of
      porous polypropylene hollow fiber membrane which was filled with water-immiscible
      organic phase. Subsequently the whole device was immersed into urine sample for
      extraction. Poly(ethylene glycol) (PEG) grafted onto multi-walled carbon
      nanotubes (PEG-g-MWCNTs) was used as extraction phase to prepare the sol-gel SPME
      fiber. Important parameters influencing the extraction efficiency such as
      desorption temperature and time, organic solvent, extraction temperature and
      time, pH, stirring speed and salt effect were investigated and optimized. Under
      the optimal conditions, the method detection limits (S/N=3) were in the range of
      0.03-0.07ngmL(-1) and the limits of quantification (S/N=10) between 0.08 and
      0.15ngmL(-1). Relative standard deviations for intra-day and inter-day precisions
      were 4.8-9.0% and 4.9-8.1%, respectively. Subsequently, the method was
      successfully applied to human urine fractions after administration of ibuprofen,
      naproxen and diclofenac.

PMID- 23122404
TI  - Bioanalytical method validation of rapamycin in ocular matrix by QTRAP LC-MS/MS:
      application to rabbit anterior tissue distribution by topical administration of
      rapamycin nanomicellar formulation.
AB  - A novel, fast and sensitive 3200 QTRAP LC-MS/MS method was validated for
      rapamycin analysis in the rabbit eye following 0.2% administration of
      nanomicellar eye drop formulation. The LC-MS/MS technique was developed with
      electrospray ionization (ESI) in positive mode. Rapamycin was extracted from
      individual eye tissues and fluids by a simple protein precipitation method.
      Samples were reconstituted in 200MUL of 80% of acetonitrile in water containing
      0.05% formic acid. Twenty microliter of the sample was injected on LC-MS/MS.
      Chromatographic separations was achieved on reversed phase C 8 Xterra column,
      50mm*4.6mm, 5MUm. Multiple reactions monitoring (MRM) transition m/z 936.6/409.3
      for rapamycin and 734.4/576.5 for erythromycin were employed as internal
      standard. The calibration curves were linear r(2)>0.9998 over the concentration
      range from 2.3ng/mL to 1000.0ng/mL. Rapamycin was found to be stable in ocular
      tissue homogenates for 6weeks at a refrigerated -80 degrees C and -20 degrees C
      temperatures. Rapamycin concentration was found to be 2260.7+/-507.1 (mean+/
      S.D.)ng/g tissue and 585.5+/-80.1 (mean+/-S.D.)ng/g tissue in the cornea and iris
      ciliary muscle, respectively. This method has two advantages. First, a volatile
      base was used in the extraction procedure, which is easy to evaporate and
      generate consistent results. Second, the sodium adduct is employed that was
      stable in non-ammoniated mobile phase. The method demonstrates that absorption of
      rapamycin by a topical application of 0.2% rapamycin nanomicellar formulation
      generates therapeutically effective concentrations in the anterior segment of the
      eye.

PMID- 23122405
TI  - Determination of piperphentonamine and metabolites M1 and M6 in human plasma and
      urine by LC/MS/MS and its application in a pharmacokinetics study in Chinese
      healthy volunteers.
AB  - Piperphentonamine hydrochloride (PPTA) is a new calcium sensitizer. A liquid
      chromatography-tandem mass spectrometry (LC/MS/MS) method for determination of
      piperphentonamine and its metabolites M1 and M6 was developed for the first time
      and applied to a pharmacokinetics study. Protein precipitation was used for pre
      treatment of plasma samples, and solid phase extraction method was used for pre
      treatment of urine samples. The chromatographic separation was achieved on a
      C(18) column using gradient elution in this study: A: 1% acetic acid aqueous
      solution, and B: acetonitrile. The whole analysis lasted for 10.5min and the
      gradient flow rate was 0.25mL/min constantly. The detection was performed of a
      triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM)
      mode via a positive electrospray ionization source. The results were that the m/z
      ratios of monitored precursor ions and product ions of PPTA, M1 and M6 were 354.0
      >191.8, 356.0->148.7 and 358.0->148.7, respectively. From the standard curve, the
      concentration ranges of both PPTA and M1 in blood and urine samples were 0.1
      500ng/mL and 0.1-200ng/mL, respectively; the concentration ranges of M6 in blood
      sample and urine sample were 0.2-500ng/mL and 0.2-200ng/mL, respectively; and the
      correlation coefficient of standard curve was r>0.99. A total of 31 healthy
      Chinese subjects participated in the pharmacokinetic study of single bolus
      intravenous injection of piperphentonamine hydrochloride. They were divided into
      three dosage groups and given 0.2, 0.4 and 0.6mg/kg of PPTA. After drug
      administration, concentrations of PPTA, M1 and M6 in human plasma and urine
      samples were determined to evaluation the pharmacokinetic characteristics of PPTA
      and its metabolites M1 and M6.

PMID- 23122406
TI  - Capillary electrophoresis to quantitate gossypol enantiomers in cotton flower
      petals and seed.
AB  - Gossypol is a toxic compound that occurs as a mixture of enantiomers in cotton
      plant tissues including seed and flower petals. The (-)-enantiomer is more toxic
      to non-ruminant animals. Efforts to breed cottonseed with a low percentage of (-)
      gossypol requires determination of the (+)- to (-)-gossypol ratio in seed and
      flower petals. We report a method to quantitatively determine the total gossypol
      and percent of its enantiomers in cotton tissues using high performance capillary
      electrophoresis (HPCE). The method utilizes a borate buffer at pH 9.3 using a
      capillary with internal diameter of 50MUm, effective length of 24.5cm, 15kV and
      cassette temperature of 15 degrees C. This method provides high accuracy and
      reproducible results with a limit of detection of the individual enantiomers of
      less than 36ng/mL providing base line separation in less than 6min.

PMID- 23122407
TI  - Microfractionation bioactivity-based ultra performance liquid
      chromatography/quadrupole time-of-flight mass spectrometry for the identification
      of nuclear factor-kappaB inhibitors and beta2 adrenergic receptor agonists in an
      alkaloidal extract of the folk herb Alstonia scholaris.
AB  - Traditional Chinese medicines (TCMs) are generally considered complementary or
      alternative remedies in most Western countries. The constituents of TCMs are hard
      to define, and their efficacy is difficult to appraise. Thus, the development of
      suitable methods for evaluating the relationship between bioactivity and the
      chemical makeup of complex TCM mixtures remains a great challenge. In the present
      work, the bioactivity-integrated fingerprints of alkaloidal leaf extracts of
      Alstonia scholaris, a folk medicinal herb for chronic respiratory diseases, were
      established by ultra performance liquid chromatography/quadrupole time-of-flight
      mass spectrometry (UPLC-Q/TOF). This method was coupled with two dual-luciferase
      reporter assay systems to show nuclear factor-kappaB (NF-kappaB) inhibition and
      beta(2) adrenergic receptor (beta(2)AR) activation. Using UPLC-Q/TOF, 18
      potential candidates were identified according to unique mass spectrometric
      fragmentation. After in vitro biological evaluation, several indole alkaloids
      with anti-inflammatory and anti-asthmatic properties were found, including
      akuammidine, (E)-alstoscholarine, and (Z)-alstoscholarine. Compared with
      conventional fingerprints, the microfractionation based bioactivity-integrated
      fingerprints that contain both chemical and bioactivity details offer a more
      comprehensive understanding of the chemical makeup of plant materials. This
      strategy clearly demonstrated that dual bioactivity-integrated fingerprinting is
      a powerful tool for the improved screening and identification of potential dual
      target lead compounds in complex herbal medicines.

PMID- 23122408
TI  - Folding and dimerization kinetics of bone morphogenetic protein-2, a member of
      the transforming growth factor-beta family.
AB  - The kinetics of folding and dimerization of bone morphogenetic protein-2 (BMP-2),
      a disulfide-connected, homodimeric cystine-knot protein and a member of the
      transforming growth factor-beta superfamily, was analyzed under a variety of
      different conditions. Refolding and dimerization of BMP-2 were extremely slow
      under all conditions studied, and could be described by consecutive first-order
      reactions involving at least one long-lived intermediate. The rate constants vary
      from ~ 0.2 * 10(-5) to ~ 3.5 * 10(-5) s(-1), and were strongly dependent on
      temperature, redox conditions, and the presence of stabilizing or destabilizing
      ions. In particular, the combined impact of ionic strength and redox conditions
      on the rates indicates that electrostatic interactions control thiol-disulfide
      exchange reactions on the path from the unfolded and reduced monomers to the
      disulfide-connected growth factor in a rate-determining way.

PMID- 23122409
TI  - Nutritional value and influence of the thermal processing on a traditional
      Portuguese fermented sausage (alheira).
AB  - Alheiras are a traditional, smoked, fermented meat sausage, produced in Portugal,
      with an undeniable cultural and gastronomic legacy. In this study, we assessed
      the nutritional value of this product, as well as the influence of different
      types of thermal processing. Alheiras from Mirandela were submitted to six
      different procedures: microwave, skillet, oven, charcoal grill, electric fryer
      and electric grill. Protein, fat, carbohydrate, minerals, NaCl, and cholesterol
      contents, as well as fatty acid profile were evaluated. The results show that
      alheiras are not hypercaloric but an unbalanced foodstuff (high levels of
      proteins and lipids) and the type of processing has a major impact on their
      nutritional value. Charcoal grill is the healthiest option: less fat (12.5 g/100
      g) and cholesterol (29.3 mg/100 g), corresponding to a lower caloric intake
      (231.8 kcal, less 13% than the raw ones). Inversely, fried alheiras presented the
      worst nutritional profile, with the highest levels of fat (18.1 g/100 g) and
      cholesterol (76.0 g/100 g).

PMID- 23122410
TI  - Legislative style and judicial discretion: the case of guardianship law.
AB  - The criteria for appointment of a guardian, and the powers that the guardian will
      be given depend upon how a particular political entity balances respect for the
      individual's right to autonomy on the one hand, against society's desire to
      protect those who cannot manage their own affairs, on the other. In recent
      decades, the balance has tipped from concern about protection to concern about
      autonomy. This shift, in turn, has resulted in an evolution in the linguistic
      style of the laws enacted. This article examines many different guardianship
      statutes from around the United States, demonstrating that subtle linguistic
      maneuvers in the style of drafting affects the degree of discretion given to
      decision makers. Using advances in the psychology of concepts and categories, the
      article demonstrates the descriptive inadequacy of the classical distinction of
      rules versus standards in legislative drafting, and adds prototype-based laws and
      laws dependent upon enriched mental models to types of laws that legislators
      employ. The goal of the article is to build a self-conscious awareness of the
      tools available to policy-makers in their efforts to hone legislation in this
      important area of mental health law.

PMID- 23122412
TI  - Senescence marker protein 30 deficiency increases Parkinson's pathology by
      impairing astrocyte activation.
AB  - Senescence marker protein 30 (SMP30) was recently identified as gluconolactonase,
      which is involved in vitamin C (VC) biosynthesis. Therefore, the antioxidant
      property of SMP30 is thought to be mediated by its gluconolactonase function.
      However, pathologic effects of SMP30 deficiency independent of VC biosynthesis
      have not been studied in models of neurodegenerative diseases. In the present
      study, we evaluated the effect of SMP30 deficiency on Parkinson's disease (PD) in
      SMP30 knockout (KO) mice. Wild type and SMP30 KO mice supplemented with VC were
      treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Our results
      showed that MPTP-induced dopaminergic neuronal loss and motor function impairment
      were more significant in the SMP30 KO mice. Reactive oxygen species generation
      and microglia activation were higher in MPTP-treated SMP30 KO mice. However,
      SMP30 deficiency mitigated MPTP-induced astrocyte activation and glia-derived
      neurotrophic factor production. Cultures of astrocytes recovered from wild type
      and SMP30 KO mice revealed that SMP30 deficiency abolished 1-methyl-4-phenyl
      pyridinium-induced astroglial activation by blocking the extracellular signal
      regulated kinase pathway. Taken together, our findings demonstrate for the first
      time that SMP30 deficiency increases the severity of PD and suggest a beneficial
      role of SMP30 in protective astrocyte activation in response to
      neurodegeneration. The present study shows that modulation of astrocytic SMP30
      can be a promising target for treating PD.

PMID- 23122411
TI  - Medication incident reporting in residential aged care facilities: limitations
      and risks to residents' safety.
AB  - BACKGROUND: Medication incident reporting (MIR) is a key safety critical care
      process in residential aged care facilities (RACFs). Retrospective studies of
      medication incident reports in aged care have identified the inability of
      existing MIR processes to generate information that can be used to enhance
      residents' safety. However, there is little existing research that investigates
      the limitations of the existing information exchange process that underpins MIR,
      despite the considerable resources that RACFs' devote to the MIR process. The aim
      of this study was to undertake an in-depth exploration of the information
      exchange process involved in MIR and identify factors that inhibit the collection
      of meaningful information in RACFs. METHODS: The study was undertaken in three
      RACFs (part of a large non-profit organisation) in NSW, Australia. A total of 23
      semi-structured interviews and 62 hours of observation sessions were conducted
      between May to July 2011. The qualitative data was iteratively analysed using a
      grounded theory approach. RESULTS: The findings highlight significant gaps in the
      design of the MIR artefacts as well as information exchange issues in MIR process
      execution. Study results emphasized the need to: a) design MIR artefacts that
      facilitate identification of the root causes of medication incidents, b)
      integrate the MIR process within existing information systems to overcome key
      gaps in information exchange execution, and c) support exchange of information
      that can facilitate a multi-disciplinary approach to medication incident
      management in RACFs. CONCLUSIONS: This study highlights the advantages of viewing
      MIR process holistically rather than as segregated tasks, as a means to identify
      gaps in information exchange that need to be addressed in practice to improve
      safety critical processes.

PMID- 23122413
TI  - Tissue transglutaminase colocalizes with extracellular matrix proteins in
      cerebral amyloid angiopathy.
AB  - Cerebral amyloid angiopathy (CAA) is a key histopathological hallmark of
      Alzheimer's disease (AD) and hereditary cerebral hemorrhage with amyloidosis of
      the Dutch type (HCHWA-D). CAA is characterized by amyloid-beta (Abeta)
      depositions and remodeling of the extracellular matrix (ECM) in brain vessels and
      plays an important role in the development and progression of both AD and HCHWA
      D. Tissue transglutaminase (tTG) modulates the ECM by molecular cross-linking of
      ECM proteins. Here, we investigated the distribution pattern, cellular source,
      and activity of tTG in CAA in control, AD, and HCHWA-D cases. We observed
      increased tTG immunoreactivity and colocalization with Abeta in the vessel wall
      in early stage CAA, whereas in later CAA stages, tTG and its cross-links were
      present in halos enclosing the Abeta deposition. In CAA, tTG and its cross-links
      at the abluminal side of the vessel were demonstrated to be either of astrocytic
      origin in parenchymal vessels, of fibroblastic origin in leptomeningeal vessels,
      and of endothelial origin at the luminal side of the deposited Abeta.
      Furthermore, the ECM proteins fibronectin and laminin colocalized with the tTG
      positive halos surrounding the deposited Abeta in CAA. However, we observed that
      in situ tTG activity was present throughout the vessel wall in late stage CAA.
      Together, our data suggest that tTG and its activity might play a differential
      role in the development and progression of CAA, possibly evolving from direct
      modulation of Abeta aggregation to cross-linking of ECM proteins resulting in ECM
      restructuring.

PMID- 23122414
TI  - Protein aggregation caused by aminoglycoside action is prevented by a hydrogen
      peroxide scavenger.
AB  - Protein mistranslation causes growth arrest in bacteria, mitochondrial
      dysfunction in yeast, and neurodegeneration in mammals. It remains poorly
      understood how mistranslated proteins cause such cellular defects. Here we
      demonstrate that streptomycin, a bactericidal aminoglycoside that increases
      ribosomal mistranslation, induces transient protein aggregation in wild-type
      Escherichia coli. We further determined the aggregated proteome using label-free
      quantitative mass spectrometry. To identify genes that reduce cellular
      mistranslation toxicity, we selected from an overexpression library protein
      products that increased resistance against streptomycin and kanamycin. The
      selected proteins were significantly enriched in members of the oxidation
      reduction pathway. Overexpressing one of these proteins, alkyl hydroperoxide
      reductase subunit F (a protein defending bacteria against hydrogen peroxide), but
      not its inactive mutant suppressed aggregated protein formation upon streptomycin
      treatment and increased aminoglycoside resistance. This work provides in-depth
      analyses of an aggregated proteome caused by streptomycin and suggests that
      cellular defense against hydrogen peroxide lowers the toxicity of mistranslation.

PMID- 23122415
TI  - Histone H2A.Z controls a critical chromatin remodeling step required for DNA
      double-strand break repair.
AB  - Chromatin remodeling during DNA double-strand break (DSB) repair is required to
      facilitate access to and repair of DSBs. This remodeling requires increased
      acetylation of histones and a shift in nucleosome organization to create open,
      relaxed chromatin domains. However, the underlying mechanism driving changes in
      nucleosome structure at DSBs is poorly defined. Here, we demonstrate that histone
      H2A.Z is exchanged onto nucleosomes at DSBs by the p400 remodeling ATPase. H2A.Z
      exchange at DSBs shifts the chromatin to an open conformation and is required for
      acetylation and ubiquitination of histones and for loading of the brca1 complex.
      H2A.Z exchange also restricts single-stranded DNA production by nucleases and is
      required for loading of the Ku70/Ku80 DSB repair protein. H2A.Z exchange
      therefore promotes specific patterns of histone modification and reorganization
      of the chromatin architecture, leading to the assembly of a chromatin template
      that is an efficient substrate for the DSB repair machinery.

PMID- 23122417
TI  - Comparing the use of, and considering the need for, lumbar puncture in children
      with influenza or other respiratory virus infections.
AB  - BACKGROUND: The clinical presentation of influenza in infancy may be similar to
      serious bacterial infection and be investigated with invasive procedures like
      lumbar puncture (LP), despite very limited evidence that influenza occurs
      concomitantly with bacterial meningitis, perhaps because the diagnosis of
      influenza is very often not established when the decision to perform LP is being
      considered. METHODS: A retrospective medical record review was undertaken in all
      children presenting to the Children's Hospital at Westmead, Sydney, Australia, in
      one winter season with laboratory-confirmed influenza or other respiratory virus
      infections (ORVIs) but excluding respiratory syncytial virus, to compare the use
      of, and reflect on the need for, the performance of invasive diagnostic
      procedures, principally LP, but also blood culture, in influenza and non
      influenza cases. We also determined the rate of concomitant bacterial meningitis
      or bacteraemia. FINDINGS: Of 294 children, 51% had laboratory-confirmed influenza
      and 49% had ORVIs such as parainfluenza viruses (34%) and adenoviruses (15%). Of
      those with influenza, 18% had a LP and 71% had a blood culture performed compared
      with 6.3% and 55.5% in the ORVI group (for both P<0.01). In multivariate
      analysis, diagnosis of influenza was a strong independent predictor of both LP
      (P=0.02) and blood culture (P=0.05) being performed, and, in comparison with
      ORVIs, influenza cases were almost three times more likely to have a LP performed
      on presentation to hospital. One child with influenza (0.9%) had bacteraemia and
      none had meningitis. INTERPRETATION: Children with influenza were more likely to
      undergo LP on presentation to hospital compared with those presenting with ORVIs.
      If influenza is confirmed on admission by near-patient testing, clinicians may be
      reassured and less inclined to perform LP, although if meningitis is clinically
      suspected, the clinician should act accordingly. We found that the risk of
      bacterial meningitis and bacteraemia was very low in hospitalised children with
      influenza and ORVIs. A systematic review should be performed to investigate this
      across a large number of settings.

PMID- 23122418
TI  - Isolated sternum fracture with no direct trauma.

PMID- 23122419
TI  - Oral pure tramadol exposure like other opioids can cause apnea--why not be
      careful?

PMID- 23122416
TI  - Bioenergy grass feedstock: current options and prospects for trait improvement
      using emerging genetic, genomic, and systems biology toolkits.
AB  - For lignocellulosic bioenergy to become a viable alternative to traditional
      energy production methods, rapid increases in conversion efficiency and biomass
      yield must be achieved. Increased productivity in bioenergy production can be
      achieved through concomitant gains in processing efficiency as well as genetic
      improvement of feedstock that have the potential for bioenergy production at an
      industrial scale. The purpose of this review is to explore the genetic and
      genomic resource landscape for the improvement of a specific bioenergy feedstock
      group, the C4 bioenergy grasses. First, bioenergy grass feedstock traits relevant
      to biochemical conversion are examined. Then we outline genetic resources
      available bioenergy grasses for mapping bioenergy traits to DNA markers and
      genes. This is followed by a discussion of genomic tools and how they can be
      applied to understanding bioenergy grass feedstock trait genetic mechanisms
      leading to further improvement opportunities.

PMID- 23122420
TI  - Artificial neural networks in the diagnosis of acute appendicitis: should imaging
      be a part of it?

PMID- 23122421
TI  - Safety of beta-blockers in the acute management of cocaine-associated chest pain.
AB  - BACKGROUND: Cocaine is the most commonly abused illegal drug in patients
      presenting to emergency departments (EDs) because of chest pain and accounts for
      almost 40% of all drug-related visits. It is not known whether all beta-blockers
      (BB) and beta1-selective agents or mixed alpha1/beta-adrenergic antagonists
      (alpha1/beta-BB) are safe in the acute management of cocaine-associated chest
      pain, due to concerns of unopposed alpha-receptor activity resulting in coronary
      artery spasm and hypertensive urgency. METHODS: Patients who presented to the EDs
      of 2 large inner city hospitals because of chest pain and who tested positive for
      cocaine were identified by retrospective chart review. Demographic
      characteristics, symptoms, vital signs, electrocardiographic abnormalities,
      medication use, comorbidities, and troponin values were documented. The presence
      and type of BB used were studied in relation to peak elevation in troponin T and
      troponin I. Troponin elevation was defined as a troponin I greater than 0.6 ng/mL
      and troponin T greater than 0.1 ng/mL if serum creatinine was less than 2 mg/dL.
      RESULTS: A total of 378 patients were included in the study; of these, 78% (n =
      296) were black; 12% (n = 44), white; and 10% (n = 38), of other race. Twelve
      percent (n = 46) of the patients had typical chest pain, 22% (n = 84) had
      coronary artery disease, 56% (n = 213) had hypertension, and 21% (n = 79) had
      diabetes mellitus. The admission electrocardiogram showed changes (ST elevation,
      ST depression, or T-wave inversion) in 43% (n = 163) of the patients. beta
      Blockers were used in 43% (n = 162) of the encounters. Troponin elevation
      occurred in 11% (n = 42) of patients. There was no difference in the number of
      patients with troponin rise in the BB and non-BB groups, 22 of 162 vs 20 of 213
      (P = .2). There was no difference in mean peak troponin levels in patients with
      troponin rise who were treated with BB vs no BB, 6.7 vs 5.7 ng/mL (P = .6). There
      was no difference in mean peak troponin levels in patients with troponin rise who
      were treated with a beta1-selective agents vs a alpha1/beta-BB, 7.5 vs 4.1 ng/mL
      (P = .4). No cases of hypertensive urgency were identified after taking any BB.
      CONCLUSION: Troponin rise is not uncommon in patients with cocaine-associated
      chest pain and occurred in 11% of the patients. In patients with cocaine
      associated chest pain, BBs did not appear to change the incidence of troponin
      rise. beta1-Selective BBs did not appear to worsen troponin levels compared with
      mixed alpha1/beta-BB.

PMID- 23122422
TI  - What is the problem? Imaging or something else.

PMID- 23122425
TI  - Protein dynamics--a moving target: comment on "Comparing proteins by their
      internal dynamics: exploring structure-function relationships beyond static
      structural alignments" by C. Micheletti.

PMID- 23122423
TI  - Effectiveness of subsidies in promoting healthy food purchases and consumption: a
      review of field experiments.
AB  - OBJECTIVE: To systematically review evidence from field interventions on the
      effectiveness of monetary subsidies in promoting healthier food purchases and
      consumption. DESIGN: Keyword and reference searches were conducted in five
      electronic databases: Cochrane Library, EconLit, MEDLINE, PsycINFO and Web of
      Science. Studies were included based on the following criteria: (i) intervention:
      field experiments; (ii) population: adolescents 12-17 years old or adults 18
      years and older; (iii) design: randomized controlled trials, cohort studies or
      pre-post studies; (iv) subsidy: price discounts or vouchers for healthier foods;
      (v) outcome: food purchases or consumption; (vi) period: 1990-2012; and (vii)
      language: English. Twenty-four articles on twenty distinct experiments were
      included with study quality assessed using predefined methodological criteria.
      SETTING: Interventions were conducted in seven countries: the USA (n 14), Canada
      (n 1), France (n 1), Germany (n 1), Netherlands (n 1), South Africa (n 1) and the
      UK (n 1). Subsidies applied to different types of foods such as fruits,
      vegetables and low-fat snacks sold in supermarkets, cafeterias, vending machines,
      farmers' markets or restaurants. SUBJECTS: Interventions enrolled various
      population subgroups such as school/ university students, metropolitan transit
      workers and low-income women. RESULTS: All but one study found subsidies on
      healthier foods to significantly increase the purchase and consumption of
      promoted products. Study limitations include small and convenience samples, short
      intervention and follow-up duration, and lack of cost-effectiveness and overall
      diet assessment. CONCLUSIONS: Subsidizing healthier foods tends to be effective
      in modifying dietary behaviour. Future studies should examine its long-term
      effectiveness and cost-effectiveness at the population level and its impact on
      overall diet intake.

PMID- 23122424
TI  - The "Mevalonate hypothesis": a cholesterol-independent alternative for the
      etiology of atherosclerosis.
AB  - The "cholesterol hypothesis" is the leading theory to explain the cause of
      atherosclerosis. The "cholesterol hypothesis" assumes that plasma (LDL)
      cholesterol is an important causal factor for atherosclerosis.However, data of at
      least seven placebo controlled randomized prospective trials with various
      cholesterol lowering drugs show that plasma cholesterol lowering does not
      necessarily lead to protection against cardiovascular disease. Therefore an
      alternative hypothesis for the etiology of cardiovascular disease is formulated.
      This alternative hypothesis, the "mevalonate hypothesis", assumes that after
      stimulation of the mevalonate pathway in endothelial cells by inflammatory
      factors, these cells start producing cholesterol and free radicals. In this
      hypothesis, only the latter play a role in the etiology of atherosclerosis by
      contributing to the formation of oxidized cholesterol which is a widely accepted
      causal factor for atherosclerosis.Regardless of how the mevalonate pathway is
      activated (by withdrawal of statin drugs, by inflammatory factors or indirectly
      by reduced intracellular cholesterol levels) in all these cases free radical
      production is observed as well as cardiovascular disease. Since in the
      "mevalonate hypothesis" cholesterol is produced at the same time as the free
      radicals causing atherosclerosis, this hypothesis provides an explanation for the
      correlation which exists between cardiovascular disease and plasma cholesterol
      levels. From an evolutionary perspective, concomitant cholesterol production and
      free radical production in response to inflammatory factors makes sense if one
      realizes that both activities potentially protect cells and organisms from
      infection by gram-negative bacteria.In conclusion, data have been collected which
      suggest that activation of the mevalonate pathway in endothelial cells is likely
      to be a causal factor for atherosclerosis. This "mevalonate hypothesis" provides
      a better explanation for results obtained from recent clinical studies with
      cholesterol lowering drugs than the "cholesterol hypothesis". Furthermore, this
      hypothesis explains how cholesterol can be correlated with cardiovascular disease
      without being a causal factor for it. Finally it provides a logical explanation
      for the etiology of this disease.

PMID- 23122426
TI  - Expression of steroid 5alpha-reductase isozymes in prostate of adult rats after
      environmental stress.
AB  - The elevated incidence of prostate cancer and benign prostatic hypertrophy is a
      cause of increasing public health concern in the Western world. The normal and
      pathological growth of the prostate are both dependent on stimulation by
      dihydrotestosterone, which is synthesized from circulating testosterone by two
      5alpha-reductase (5alpha-R) isozymes, 5alpha-reductase type 1 (5alpha-R1) and
      5alpha-reductase type 2 (5alpha-R2). Both isozymes have been implicated in
      prostate disease. We used quantitative RT-PCR and immunohistochemistry,
      respectively, to quantify mRNA and protein levels of 5alpha-R isozymes in the
      ventral prostate of adult rats under environmental stress conditions analogous to
      those found in some common workplace situations, i.e. artificial light, excessive
      heat, and the sensation of immobility in a small space. Transcription and
      expression levels of both 5alpha-R isozymes were significantly higher in
      environmentally stressed rats than in unstressed rats. Increased 5alpha-R isozyme
      levels may play a role in the development or maintenance of prostate disease.
      Further research is warranted to explore these effects of environmental stress on
      human health and their implications for environmental and occupational health
      policies.

PMID- 23122427
TI  - [Liver sarcoma in a patient with cirrhosis and prior hepatocellular carcinoma].

PMID- 23122428
TI  - Lung cancer signature biomarkers: tissue specific semantic similarity based
      clustering of digital differential display (DDD) data.
AB  - BACKGROUND: The tissue-specific Unigene Sets derived from more than one million
      expressed sequence tags (ESTs) in the NCBI, GenBank database offers a platform
      for identifying significantly and differentially expressed tissue-specific genes
      by in-silico methods. Digital differential display (DDD) rapidly creates
      transcription profiles based on EST comparisons and numerically calculates, as a
      fraction of the pool of ESTs, the relative sequence abundance of known and novel
      genes. However, the process of identifying the most likely tissue for a specific
      disease in which to search for candidate genes from the pool of differentially
      expressed genes remains difficult. Therefore, we have used 'Gene Ontology
      semantic similarity score' to measure the GO similarity between gene products of
      lung tissue-specific candidate genes from control (normal) and disease (cancer)
      sets. This semantic similarity score matrix based on hierarchical clustering
      represents in the form of a dendrogram. The dendrogram cluster stability was
      assessed by multiple bootstrapping. Multiple bootstrapping also computes a p
      value for each cluster and corrects the bias of the bootstrap probability.
      RESULTS: Subsequent hierarchical clustering by the multiple bootstrapping method
      (alpha = 0.95) identified seven clusters. The comparative, as well as
      subtractive, approach revealed a set of 38 biomarkers comprising four distinct
      lung cancer signature biomarker clusters (panel 1-4). Further gene enrichment
      analysis of the four panels revealed that each panel represents a set of lung
      cancer linked metastasis diagnostic biomarkers (panel 1), chemotherapy/drug
      resistance biomarkers (panel 2), hypoxia regulated biomarkers (panel 3) and lung
      extra cellular matrix biomarkers (panel 4). CONCLUSIONS: Expression analysis
      reveals that hypoxia induced lung cancer related biomarkers (panel 3), HIF and
      its modulating proteins (TGM2, CSNK1A1, CTNNA1, NAMPT/Visfatin, TNFRSF1A, ETS1,
      SRC-1, FN1, APLP2, DMBT1/SAG, AIB1 and AZIN1) are significantly down regulated.
      All down regulated genes in this panel were highly up regulated in most other
      types of cancers. These panels of proteins may represent signature biomarkers for
      lung cancer and will aid in lung cancer diagnosis and disease monitoring as well
      as in the prediction of responses to therapeutics.

PMID- 23122430
TI  - 2D and 3D anatomical analyses of hand dimensions for custom-made gloves.
AB  - Measuring hand anthropometric data for the development of good-fitting gloves is
      crucial. In pursuing higher accuracy in hand anthropometric measurements,
      scanning of hand surfaces with the aids of image analysis system to acquire
      measurements is an alternative to the manual methods. This study proposes a new
      hand measuring approach by using 2D and 3D scanning which are evaluated through
      comparisons of manual measurements. Thirty-three dimensions are measured by using
      (1) tape and calliper measurement; (2) 2D image analysis; (3) 3D image analysis
      based on ten captures; and (4) 3D image analysis based on three captures,
      respectively. Repeated-measures ANOVA, correlation analysis and RMSE are used to
      examine the results. The hand dimensions obtained from the four methods are
      highly linearly correlated. Hand data taken from 3D image analysis has no
      significant difference compared with manual measurements on hand and wrist
      circumferences, length and breadth dimension, regardless of the number of
      captures.

PMID- 23122429
TI  - Predictors of the change in the expression of emotional support within an online
      breast cancer support group: a longitudinal study.
AB  - OBJECTIVES: To explore how the expression of emotional support in an online
      breast cancer support group changes over time, and what factors predict this
      pattern of change. METHODS: We conducted growth curve modeling with data
      collected from 192 participants in an online breast cancer support group within
      the Comprehensive Health Enhancement Support System (CHESS) during a 24-week
      intervention period. RESULTS: Individual expression of emotional support tends to
      increase over time for the first 12 weeks of the intervention, but then decrease
      slightly with time after that. In addition, we found that age, living situation,
      comfort level with computer and the Internet, coping strategies were important
      factors in predicting the changing pattern of expressing emotional support.
      CONCLUSIONS: Expressing emotional support changed in a quadratic trajectory, with
      a range of factors predicting the changing pattern of expression. PRACTICAL
      IMPLICATIONS: These results can provide important information for e-health
      researchers and physicians in determining the benefits individuals can gain from
      participation in should CMSS groups as the purpose of cancer treatment.

PMID- 23122431
TI  - Clinical trial registration in physiotherapy journals: recommendations from the
      International Society of Physiotherapy Journal Editors.

PMID- 23122432
TI  - The 6-minute walk test in outpatient cardiac rehabilitation: validity,
      reliability and responsiveness--a systematic review.
AB  - BACKGROUND: The 6-minute walk test (6MWT) is a common outcome measurement in
      cardiac rehabilitation. However, a search of the literature found no established
      guidelines for use of the 6MWT in cardiac rehabilitation. OBJECTIVES: Systematic
      review of the validity, reliability and responsiveness of the 6MWT in cardiac
      rehabilitation. DATA SOURCES: OvidMEDLINE, SPORTdiscus, EMBASE, CINAHL, Cochrane
      Reviews and Cochrane Clinical Trials between January 1948 and April 2011.
      ELIGIBILITY CRITERIA: Studies using 6MWTs in subjects with coronary artery
      disease undergoing cardiac rehabilitation on an outpatient basis, published in
      English, were included. STUDY APPRAISAL AND METHODS: Quantitative and qualitative
      analyses were conducted, including quality assessment of methodology, meta
      analysis and assessment against level of evidence criteria. RESULTS: Fifteen
      articles met the inclusion criteria. One high-quality study was identified for
      reliability, six high-quality studies were identified for validity and 11 high
      quality studies were identified for responsiveness. The meta-analysis found
      strong evidence that the 6MWT was responsive to change in clinical status
      following cardiac rehabilitation, with an estimated mean difference in 6-minute
      walk distance of 60.43m (95% confidence interval 54.57 to 66.30m; P<0.001).
      Qualitative analysis indicated moderate evidence for repeatability of the 6MWT in
      patients undergoing cardiac rehabilitation, for a 2% to 8% learning effect
      between repeated 6MWTs, for a relationship between peak heart rate during the
      6MWT and during cycle exercise at the ventilatory threshold, and for moderate-to
      high correlation between the 6-minute walk distance and maximum metabolic
      equivalents achieved on symptom-limited exercise tests. LIMITATIONS: Few studies
      assessed similar aspects of validity for the 6MWT. CONCLUSION: Strong evidence
      suggests that the 6MWT is responsive to clinical change following cardiac
      rehabilitation. Intra- and intertester reliability of the 6MWT and its validity
      in patients undergoing cardiac rehabilitation requires further research.

PMID- 23122433
TI  - Clinical effectiveness of knee rehabilitation techniques and implications for a
      self-care treatment model.
AB  - BACKGROUND: Physiotherapy is a complex intervention frequently recommended for
      knee conditions. The International Classification of Functioning and Disability
      (ICF) can be used as a framework to evaluate evidence to develop care models and
      clinical guidelines. OBJECTIVE: To evaluate the clinical effectiveness of knee
      rehabilitation modalities categorised according to the ICF domains. DATA SOURCES:
      A keyword search of Medline, Cinahl, Amed, Embase and Cochrane databases from
      1996 to 2010 using terms related to the knee joint and physiotherapeutic
      interventions. STUDY SELECTION: Reviewer assessment using inclusion/exclusion
      criteria and a quality assessment tool compiled from the Critical Appraisal
      Skills Programme Tool, Consort and Cochrane Bone Joint and Muscle Trauma Groups.
      DATA EXTRACTION: Information about the research design, intervention and subjects
      was extracted. Outcome measures and findings were categorised according to ICF
      domains. DATA SYNTHESIS: The majority of studies evaluated exercise. Findings
      were supportive but specific recommendations were limited due to variations in
      content and application. There was limited quality research to support the theory
      that manual therapy, electrotherapy or taping in isolation contributes to
      recovery. Multimodality physiotherapy programmes were found to be beneficial and
      to reflect clinical practice, but the effectiveness of each component is unknown.
      Outcome measures from the participation domain of the ICF were used least
      frequently and were not generally true measures of participation. CONCLUSION:
      Development of participation outcome measures is required to evaluate the long
      term benefits of interventions. Rehabilitation should be based around delivery of
      effective exercise programmes incorporating participation outcomes to provide
      feedback and complement self-care for knee conditions.

PMID- 23122434
TI  - Effect of a high-density foam seating wedge on back pain intensity when used by
      14 to 16-year-old school students: a randomised controlled trial.
AB  - OBJECTIVES: No previous randomised controlled trials had been undertaken
      investigating the effect of school seating on back pain in 14 to 16 year olds.
      This study was designed to test the effect of the use of a high-density foam
      wedge on normal school seating on the intensity of back pain. DESIGN: Randomised
      controlled trial. SETTING: Suffolk, a predominantly rural county in eastern
      England. PARTICIPANTS: One hundred and eighty-five students with back pain were
      recruited from 12 schools. Randomisation was stratified by school. The control
      and intervention groups included 92 and 83 students, respectively. INTERVENTION:
      Following a 1-week baseline observation period, each student in the intervention
      group was given a wedge to use on their school chairs. OUTCOME MEASURE: The
      primary outcome measure was pain intensity (numerical rating scale, 0 to 10)
      recorded in pain diaries over 4 weeks. Random effects models were used to analyse
      the pain intensity data. RESULTS: Ninety-seven students (46 control group, 51
      intervention group) completed the trial. For the intervention group, pain
      intensity was reduced significantly over the 3 weeks of wedge use. The average
      reduction in pain intensity was estimated to be 0.709 points (95% confidence
      interval 0.341 to 1.077), representing a 58% reduction in back pain for those in
      the intervention group. CONCLUSION: Use of a wedge reduced the intensity of back
      pain significantly, especially in the evenings. The results suggest that further
      research into the longer-term effect of seating on pain intensity in adolescents
      should be considered.

PMID- 23122435
TI  - Effect of different angles of knee flexion on leg extensor power in healthy
      individuals.
AB  - OBJECTIVES: To investigate the effect of fixed flexion knee deformity on leg
      extensor power as measured by the Nottingham leg extensor power rig. DESIGN:
      Cross-sectional observational study. SETTING: Orthopaedic hospital. PARTICIPANTS:
      A convenience sample of 135 adult participants. MAIN OUTCOME MEASURES: leg
      extensor power normalised for body weight, UCLA activity scale. RESULTS: Power
      values at 0 degrees  FF were found to be significantly less than power values at
      15 degrees  FF [difference 0.21W/kg SD .36], and power values at 15 degrees  FF
      were significantly less than those at 30 degrees  FF [difference 0.31W/kg SD .43;
      P<0.001) in both right and left legs. Age and activity levels were moderately
      negatively correlated, with UCLA score decreasing with increasing age (-0.343,
      P<0.0005). No significant correlation was found between activity levels measured
      on the UCLA and power on the LEP. CONCLUSIONS: Given the large range of pre
      operative maximal extension, the validity of testing each patient at their own
      maximal range of pre-intervention extension and then at the same angle post
      intervention is questionable. In studies assessing change in power following an
      intervention, the end point angle should be standardised between individuals. In
      future studies investigating leg extensor power on the LEP rig pre and post
      intervention, it could be more appropriate to standardise the angle of FF to 30
      degrees , with individuals who are unable to achieve this position excluded from
      the study.

PMID- 23122436
TI  - Blowing the whistle to protect a patient: a comparison between physiotherapy
      students and physiotherapists.
AB  - OBJECTIVES: To answer three questions: Are physiotherapists and physiotherapy
      students willing to take action to prevent misconduct in order to protect a
      patient's interests? Are they willing to report the misconduct to authorities
      within an organisation and/or outside of it? Are they willing to report a
      colleague's wrongdoing as well as that of a manager? DESIGN: Observational
      questionnaire study. PARTICIPANTS: Two hundred and twenty-seven participants
      divided into two groups: 126 undergraduate students at the Department of Physical
      Therapy at Ben Gurion University, and 101 certified physiotherapists working in
      hospitals and rehabilitation centres in south and central regions of Israel.
      OUTCOME MEASURES: Participants were presented with two vignettes - one describing
      a colleague's misconduct and the other describing a manager's misconduct - and
      asked to make a decision about whistleblowing. RESULTS: Both groups rated their
      own willingness to take action to change the harmful situations very highly. The
      physiotherapists perceived a colleague's misconduct as being more serious than
      the students, and were more willing to intervene internally. The students were
      more prepared than the physiotherapists to take such action externally. The
      students perceived the manager's misconduct as being more serious than the
      physiotherapists, and also reported a greater readiness to intervene externally.
      CONCLUSIONS: Physiotherapists consider acts that are detrimental to a patient to
      be very serious, and are more willing to take action when the offending
      individual is a colleague. Students are more willing to blow the whistle
      externally. This article suggests tools for handling similar situations.

PMID- 23122437
TI  - Test-retest reliability, smallest real difference and concurrent validity of six
      different balance tests on young people with mild to moderate intellectual
      disability.
AB  - OBJECTIVES: Some studies have reported that people with intellectual disability
      may have reduced balance ability compared with the population in general.
      However, none of these studies involved adolescents, and the reliability and
      validity of balance tests in this population are not known. The purpose of this
      study was to examine the reliability of six different balance tests and to
      investigate their concurrent validity. DESIGN: Test-retest reliability
      assessment. SETTINGS: All subjects were recruited from a special school for
      people with intellectual disability in Bollnas, Sweden. PARTICIPANTS: Eighty-nine
      adolescents (35 females and 54 males) with mild to moderate intellectual
      disability with a mean age of 18 years (range 16 to 20 years). INTERVENTIONS: All
      subjects followed the same test protocol on two occasions within an 11-day
      period. MAIN OUTCOMES: Balance test performances. RESULTS: Intraclass correlation
      coefficients greater than 0.80 were achieved for four of the balance tests:
      Extended Timed Up and Go Test, Modified Functional Reach Test, One-leg Stance
      Test and Force Platform Test. The smallest real differences ranged from 12% to
      40%; less than 20% is considered to be low. Concurrent validity among these
      balance tests varied between no and low correlation. CONCLUSION: The results
      indicate that these tests could be used to evaluate changes in balance ability
      over time in people with mild to moderate intellectual disability. The low
      concurrent validity illustrates the importance of knowing more about the
      influence of various sensory subsystems that are significant for balance among
      adolescents with intellectual disability.

PMID- 23122438
TI  - Importance of correcting for individual differences in the clinical diagnosis of
      gait disorders.
AB  - OBJECTIVE: To quantify the effects of subject characteristics on gait parameters
      using acceleration-based gait analysis. DESIGN: Cross-sectional study with a
      single group cohort. SETTING: Hospital setting. PARTICIPANTS: One hundred and
      twenty healthy subjects (six age decade groups of 10 men and 10 women) performed
      a 20-m walking test. METHODS: Basic gait parameters (e.g. speed) and other
      clinically relevant parameters (e.g. step time asymmetry) were assessed during a
      20-m walking test using a tri-axial accelerometer, attached at the level of the
      sacrum. Subject characteristics were recorded. RESULTS: Between 34% and 51% of
      the variability in gait parameters was explained by age, height and gender.
      Subject characteristics contributed less to the variance in step time asymmetry
      (R(2)=0.02), gait irregularity (R(2)=0.07) and vertical displacement of the
      centre of mass (R(2)=0.17). Relationships identified were comparable with
      previous studies (e.g. faster walking speed in men, younger and taller subjects).
      CONCLUSIONS: Age, height and gender are determinants of basic gait parameters,
      while their influence on gait irregularity and step time asymmetry is minimal.
      This indicates that gait is variable between subjects, showing the relevance of
      correcting gait for subject characteristics. This study describes preliminary
      work to build a database of gait parameters in healthy participants, describing
      the effects of age, gender and height. Further studies to extend this database
      with patients would provide further relevance to clinical practice.

PMID- 23122439
TI  - Influence of step length on 6-minute walk test performance in patients with
      chronic heart failure.
AB  - OBJECTIVE: To investigate the influence of gait parameters including step length
      and walking speed during performance of the 6-minute walking test (6MWT) in
      patients with chronic heart failure (CHF). DESIGN: Observational study. SETTING:
      Specialist heart failure clinic. PARTICIPANTS: Patients with CHF and aged
      matched, apparently healthy controls. INTERVENTIONS: Each patient and control
      performed a 6MWT following a standardised protocol in a 15m corridor. The number
      of steps (defined as step from left foot to right foot) taken every 15m was
      counted, and reported as minute-by-minute changes in 6MWT performance. In
      addition, minute-by-minute changes in time taken to complete 15m and mean walking
      speed throughout the test were calculated. MAIN OUTCOME MEASURES: Walking speed
      and step length. RESULTS: Thirty patients with CHF {87% males; mean age 75
      [standard deviation (SD) 8] years} and 10 healthy controls [80% males; mean age
      77 (SD 11) years] undertook the 6MWT. For the CHF group, the mean distance walked
      was 309 (SD 48)m and the peak Borg score was 12 (SD 1). For the controls, the
      mean distance walked was 334 (SD 138)m and the peak Borg score was 12 (SD 1).
      Patients with CHF showed no significant minute-by-minute changes in step length
      or walking speed over the course of the 6MWT. In the first 5minutes, healthy
      controls had a longer step length and faster walking speed than patients with CHF
      [step length: mean difference in the first minute was 0.03m, 95% confidence
      interval (CI) of the difference 0.01 to 0.05m; P=0.02; walking speed: mean
      difference in the first minute 0.04m/second, 95% CI of the difference 0.02 to
      0.07m/second; P=0.01]. A multiple linear regression analysis demonstrated that
      body mass index (P=0.02) was the most important predictor of 6MWT performance.
      CONCLUSION: Patients with CHF have a shorter step length and walk more slowly
      than controls during the 6MWT. Altered gait mechanics may contribute to limited
      exercise capacity in patients with CHF.

PMID- 23122440
TI  - Problem Based Learning in physiotherapy education: a practice perspective.
AB  - BACKGROUND: Problem Based Learning (PBL) has been integrated into a range of
      health education curricula; however there is limited research evaluating the
      application of skills developed through PBL in clinical practice. AIM: This study
      aimed to provide evidence of how skills gained through PBL are applied in
      practice by student physiotherapists, from the perspective of their placement
      supervisors. METHOD: A qualitative one-to-one semi-structured interview
      methodology was used, purposively recruiting a sample of 10 qualified
      physiotherapists with experience of placement supervision of students studying on
      a PBL physiotherapy undergraduate degree. RESULTS: The supervisors felt that PBL
      offered positive benefits for both student education and clinical practice. There
      was evidence of the application of skills and attributes associated with PBL,
      including positive learning behaviours and a high level of motivation and self
      direction. Supervisors felt that proactive students were able to apply
      transferable skills inherent in the PBL approach to clinical practice, including
      a holistic, problem-solving approach and effective team-working but that there
      was considerable variation between students. CONCLUSIONS: There is evidence of
      variable application of skills associated with PBL in clinical practice in this
      study group. Further research would be useful to explore the factors that enable
      students to successfully apply the attributes developed using a PBL approach into
      practice.

PMID- 23122441
TI  - Experiences of an exercise referral scheme from the perspective of people with
      chronic stroke: a qualitative study.
AB  - OBJECTIVE: To explore stroke survivors' experiences of undertaking exercise in
      the context of an exercise referral scheme for people with chronic stroke.
      DESIGN: A qualitative design, using semi-structured interviews within a
      constructivist framework to explore the experiences of individual participants.
      Verbatim transcripts were thematically analysed. Rigour mechanisms included
      respondent validation, peer checking, and reflexivity. SETTING: An exercise
      referral scheme, based at a leisure centre in South London. PARTICIPANTS: Nine
      community-dwelling stroke survivors took part; 5 male and 4 female, mean age 51
      years (range 37-61 years); time post stroke 1-4 years, with mixed ethnic
      backgrounds. FINDINGS: Participants described greater physical and psychological
      well-being following participation in the exercise referral scheme. Categories
      that emerged were: improved exercise engagement and confidence, more internalised
      perceptions of control and enhanced lifestyle, work and social roles. Categories
      linked to form a master theme, labelled: 'Exercise Referral Scheme as a catalyst
      for regaining independence.' CONCLUSIONS: This study supports the value of
      exercise referral schemes in enabling people with stroke to engage in exercise.
      For participants in this study, the scheme seemed influential in the process of
      regaining independence.

PMID- 23122442
TI  - Understanding hope in patients with Multiple Sclerosis.
AB  - OBJECTIVES: To understand how patients with Multiple Sclerosis experience and
      express hope within a rehabilitation setting and use this information to help
      therapists in a clinical setting. DESIGN: One guided interview was undertaken.
      SETTING: Two locations were used for interviews: (1) a rehabilitation centre in
      Oxfordshire. (2) A meeting location for the MS society in London. PARTICIPANTS:
      Eleven patients with Multiple Sclerosis were selected (54.5+/-8.8 years). Six
      patients were classified as being in the secondary progressive stage and 5 were
      classified as relapsing remitting phase. METHOD: The patients selected were part
      of a 12-week Multiple Sclerosis rehabilitation program. One interview took place
      mid way through the rehabilitation program and immediately following the end of
      the rehabilitation program. The semi-structured interview comprised of 5 sub
      sections. Categorical content analysis was used to analyse the results. RESULTS:
      Three main themes were identified that related to the paradox of chronic illness:
      (1) defiance and the patient (2) accepting the diagnosis and prognosis and (3)
      accepting deterioration. These themes provide a basis for the different types of
      hopes expressed by patients. CONCLUSION: It is vital to understand the paradox of
      chronic illness as an expression common among patients with Multiple Sclerosis.
      This research illustrates the importance of listening to a patient's narrative
      during rehabilitation.

PMID- 23122443
TI  - The care needs of Pakistani families caring for disabled children: how relevant
      is cultural competence?
AB  - OBJECTIVE: To identify factors that Pakistani parents living in the UK and caring
      for children with learning disabilities felt were important components of their
      care and to discuss the relevance of the concept of cultural competence in the
      light of these findings. DESIGN: A qualitative study taking a constructivist
      approach to gain insight into participants' experiences of health care provision.
      In depth interviews were used to explore the ways in which personal
      understandings and life experiences shaped the characteristics of the therapeutic
      encounter that participants identified as important. Data were analysed
      thematically. SETTING: A Northern city in England. Interviews took place in
      participant's homes or work places. PARTICIPANTS: Eleven Pakistani parents and
      one grandparent from nine different families, all caring for children with
      learning disabilities. FINDINGS: The study identified features of the therapeutic
      encounter that were important to Pakistani parents and highlighted that there is
      nothing to suggest that these are different to those of the majority population.
      CONCLUSIONS: The utility of the concept of cultural competence may be limited
      where it depends on concepts of ethnic groups as relatively fixed cultural groups
      with distinct and clearly defined sets of health beliefs and behaviours.
      Physiotherapists cannot prejudge health status and behaviours from an
      individual's ethnic status. Instead there is a need to actively seek the
      understandings that are relevant to practice. In addition health service
      providers must develop and operate systems that ensure access, use and quality of
      care are the same at the point of delivery regardless of patient ethnicity.

PMID- 23122444
TI  - Elevated plasma high-mobility group box 1 protein is a potential marker for
      neuromyelitis optica.
AB  - High-mobility group box 1 protein (HMGB1) has cytokine activities and mediates
      systemic inflammation as well as immune responses. The aim of this study was to
      determine if plasma HMGB1 level can be used as a marker for neuromyelitis optica
      (NMO) and to differentiate NMO from multiple sclerosis (MS). We measured plasma
      levels of HMGB1, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN
      gamma), and interleukin 17 (IL-17) in 29 patients with NMO and 20 patients with
      MS at enrollment and at 2years follow-up (at the time of definitive diagnosis) by
      enzyme-linked immunosorbent assay. Plasma HMGB1 level was significantly greater
      in the NMO group compared to the MS group (P<0.001). Plasma levels of TNF-alpha,
      IFN-gamma, and IL-17 were significantly greater in the NMO group compared to the
      MS group, and HMGB1 level was positively correlated with TNF-alpha, IFN-gamma,
      and IL-17 levels. Univariate logistic regression analysis showed a significant
      association of HMGB1 level, and IFN-gamma level with NMO diagnosis. Although this
      study included a limited sample size, we attempted to determine an optimized
      cutoff point for HMGB1 (>=2 ng/ml), which provided 89.7% sensitivity and 95.0%
      specificity for the diagnosis of NMO. These results indicate that plasma HMGB1
      level might serve as a surrogate marker for NMO disease activity and aid in the
      differentiation of NMO from MS at the early disease stage.

PMID- 23122445
TI  - Predictors of high-energy foods and beverages: a longitudinal study among socio
      economically disadvantaged adolescents.
AB  - OBJECTIVE: While socio-economically disadvantaged adolescents tend to have poor
      dietary intakes, some manage to eat healthily. Understanding how some
      disadvantaged adolescents restrict high-energy foods and beverages may inform
      initiatives promoting healthier diets among this population. The present
      investigation aimed to: (i) identify disadvantaged adolescents' high-energy food
      and beverage intakes; and (ii) explore cross-sectional and longitudinal
      associations between intrapersonal, social and environmental factors and
      disadvantaged adolescents' high-energy food intakes. DESIGN: Longitudinal online
      surveys were completed at baseline (2004-2005) and follow-up (2006-2007), each
      comprising a thirty-eight-item FFQ and questions examining intrapersonal, social
      and environmental factors. SETTING: Thirty-seven secondary schools in
      metropolitan and non-metropolitan Victoria, Australia. SUBJECTS: Of 1938
      adolescents aged 12-15 years participating at both time points, 529 disadvantaged
      adolescents (whose mothers had low education levels) were included in the present
      investigation. RESULTS: At baseline and follow-up, respectively 32% and 39% of
      adolescents consumed high-energy foods less frequently (<=2 high-energy food
      meals/week); 61% and 65% consumed high-energy beverages less frequently (<=1
      time/d). More girls than boys had less frequent high-energy food intakes, and
      baseline consumption frequency predicted consumption frequency at follow-up.
      Adolescents with less frequent consumption of high-energy foods and beverages
      seldom ate fast food for main meals, reported reduced availability of high-energy
      foods at home and were frequently served vegetables at dinner. CONCLUSIONS:
      Nutrition promotion initiatives could help improve disadvantaged adolescents'
      eating behaviours by promoting adolescents and their families to replace high
      energy meals with nutritious home-prepared meals and decrease home availability
      of high-energy foods in place of more nutritious foods.

PMID- 23122446
TI  - ["TVT Abbrevo((r)) procedure: don't forget to remove the set of positioning
      line!"].

PMID- 23122447
TI  - [Technical aspects of elective repeat caesarean delivery].

PMID- 23122448
TI  - [Anesthetic management in case of previous cesarean section].
AB  - An efficient communication between the obstetrics and anesthesiology teams is a
      prerequisite for an optimal management of a woman with a previous cesarean
      section (professional agreement). Epidural analgesia should be encouraged in this
      context due to a high risk of emergency obstetrical procedures, in order to avoid
      general anesthesia (professional agreement). When possible, spinal anesthesia is
      the technique of choice for elective repeat cesarean delivery even in case of
      morbidly adherent placenta (professional agreement).

PMID- 23122450
TI  - Urosdeoxycholic acid in primary sclerosing cholangitis: a meta-analysis and
      systematic review.
AB  - BACKGROUND AND STUDY AIMS: Primary sclerosing cholangitis (PSC) is a chronic
      cholestatic liver disease with no proven effective medical therapy.
      Ursodeoxycholic acid (UDCA) was proposed as a potential treatment for this
      disorder. However, several randomised controlled trials reported conflicting
      results regarding the usefulness of UDCA. The aim of this meta-analysis and
      systematic review is to investigate the efficacy of UDCA in PSC. PATIENTS AND
      METHODS: Literature review was performed to include randomised controlled trials
      and non-randomised studies comparing UDCA to a placebo in PSC. The included
      controlled trials were assigned a quality score. Random effects model was used.
      Outcomes were measured with Weight Mean Difference, Risk Ratio or Risk
      Difference. Heterogeneity was measured by I(2) measure of inconsistency. RESULTS:
      Seven RCTs satisfied the inclusion criteria with a total number of 553 patients.
      Low dose UDCA was used in 4 studies, high dose UDCA (17-30mg/kg) was used in
      three studies. UDCA did not decrease the risk of mortality compared to placebo
      (RR=1.04, 95% CI 0.46-2.35) or the need for liver transplant (RR=1.22, 95% CI 0.7
      2.12). UDCA also had no effect on the clinical symptoms. Liver Function Tests
      (LFTs) were significantly improved in the UDCA treated patients. UDCA did not
      decrease the incidence of cholangiocarcinoma. CONCLUSION: UDCA had no beneficial
      effect on the patients' survival, liver histology, prevention of
      cholangiocarcinoma, or improvement of clinical symptoms. High dose UDCA was
      associated with increased mortality in one of the large randomised trial included
      in this analysis.

PMID- 23122449
TI  - eNOS genotype modifies the effect of leisure-time physical activity on serum
      triglyceride levels in a Japanese population.
AB  - BACKGROUND: Nitric oxide is a key molecule not only in the cardiovascular system,
      but also in the metabolic-endocrine system. The purpose of this study was to
      examine possible associations of the NOS3 T-786C polymorphism (rs2070744) with
      serum lipid levels on the basis of lifestyle factors for tailoring prevention of
      dyslipidemia. METHODS: For this cross-sectional study, a total of 2226 subjects
      aged 35 to 69 years (1084 men and 1142 women) were selected from Japanese
      participants in the Japan Multi-Institutional Collaborative Cohort (J-MICC)
      Study. They were recruited in eight areas throughout Japan between February 2004
      and November 2008. RESULTS: In a stratified analysis by leisure-time physical
      activity, the likelihood of hypertriglyceridemia (serum triglyceride levels >=
      150 mg/dL) among subjects with the C allele was significantly lower than those
      without it in the active group (OR = 0.43, 95% CI = 0.22-0.84 in the fasting
      group), but not in the sedentary group. A gene-environment interaction between
      the T-786C polymorphism and leisure-time physical activity for
      hypertriglyceridemia was significant (P = 0.007 in the fasting group).
      Additionally, serum triglyceride levels (mean +/- SD) across leisure-time
      physical activity classes decreased significantly only in the TC + CC genotype
      group (111 +/- 60 mg/dL for sedentary, 95 +/- 48 mg/dL for moderately active, 88
      +/- 44 mg/dL for very active, P for trend = 0.008 in the fasting group), but not
      in the TT genotype group. Total cholesterol, high-density lipoprotein (HDL)
      cholesterol, and non-HDL cholesterol levels had no significant association with
      the polymorphism. CONCLUSIONS: This study suggests that the NOS3 T-786C
      polymorphism modifies the effect of leisure-time physical activity on serum
      triglyceride levels.

PMID- 23122451
TI  - Is serum level of methylated RASSF1A valuable in diagnosing hepatocellular
      carcinoma in patients with chronic viral hepatitis C?
AB  - BACKGROUND AND STUDY AIMS: The detection of the promoter hypermethylation of
      RASSF1A in serum DNA could be a valuable biomarker for early detection of
      preneoplastic lesions and early cancer development among high-risk populations
      who are at a high risk of hepatocellular carcinoma (HCC). Therefore, we aimed
      determining the serum level of methylated RASSF1A sequence in patients with
      chronic hepatitis C viral infection and to evaluate the predictive value of it as
      a diagnostic marker for HCC in patients with chronic hepatitis C viral infection.
      PATIENTS AND METHODS: Serum levels of methylated RASSF1A were detected and
      measured using real-time PCR after digestion with a methylation-sensitive
      restriction enzyme in 40 patients with chronic HCV infection, 40 patients with
      HCC (on top of HCV) and 20 controls. RESULTS: Methylated RASSF1A was detected in
      10% of the controls, 62.5% of HCV group and in 90% of HCC group. Chronic HCV
      patients had insignificantly higher levels than the controls. The levels were
      significantly higher in patients with HCC compared to the controls (p=0.0001) and
      chronic HCV patients (p=0.001). By logistic regression analysis, the serum
      methylated RASSF1A was found to differentiate HCC patients from healthy controls
      with an AUROC of 0.83nmol/L, and an overall predictive accuracy of 77.5%. It was
      able to differentiate patients with HCC from those with chronic HCV infection
      alone with an AUROC of 0.733 and an overall predictive accuracy of 72.5%.
      CONCLUSION: The mean serum levels of methylated RASSF1A could be of value for
      early diagnosis of HCC especially in high risk patients with HCV infection.

PMID- 23122452
TI  - Role of peritoneal ultrasonography and ultrasound-guided fine needle aspiration
      cytology/biopsy of extravisceral masses in the diagnosis of ascites of
      undetermined origin.
AB  - BACKGROUND AND STUDY AIMS: Ascites may be of undetermined origin despite
      comprehensive study. This study aimed to assess the accuracy and safety of
      conventional and interventional high-frequency peritoneal ultrasound in the
      diagnosis of patients with ascites of unclear origin. PATIENTS AND METHODS: A
      total of 62 patients were prospectively enrolled; they underwent conventional
      (3.5-5MHz) and high-frequency (6-8MHz) transabdominal peritoneal ultrasound to
      suggest the nature of ascites supplemented by fine needle aspiration cytology
      (FNAC) of ascites and/or core biopsy of the omentum or other extra-visceral
      masses for final histopathologic diagnosis. Laparoscopy or laparotomy was needed
      if biopsy was inconclusive. RESULTS: Ultrasound-guided procedures were diagnostic
      in 55 (87.7%) patients. Thirty-six (58.1%) were benign, of whom 86% had
      tuberculous peritonitis, 26 (41.9%) were malignant, of whom 76.9% had peritoneal
      metastasis. High-frequency ultrasound was able to propose ultrasonographic
      criteria in a trial to diagnose the nature of ascites. Our proposed
      ultrasonographic criteria were based on the amount and texture of ascites in
      addition to the omental and mesenteric features. These were able to suggest the
      diagnosis with 80.7% sensitivity for malignant ascites and 75% specificity for
      benign ascites. Moreover, histopathological examination of tissues obtained by
      ultrasound-guided procedures increased the sensitivity to 88.5% and the
      specificity to 88.9% in diagnosing malignant and benign disease, respectively,
      with an overall diagnostic accuracy of 88.6%. These procedures were considered to
      be safe as only one major (haemoperitoneum) and two minor complications
      (temporary ascitic fistula) were reported. CONCLUSION: High-frequency peritoneal
      ultrasound together with the minimally invasive ultrasound-guided FNAC/biopsy of
      extra-visceral lesions may be considered an effective and safe tool in the
      diagnosis of ascites of undetermined origin.

PMID- 23122453
TI  - The initial experience of safety and efficacy of argon plasma coagulation (APC)
      in the primary prevention of variceal bleeding.
AB  - BACKGROUND AND STUDY AIMS: The well-known complications of variceal bleeding
      together with the high mortality rate mandate effective prophylaxis. Because of
      the intolerance, failure of response and lack of compliance related to B blockers
      and because of the high incidence of variceal recurrence after endoscopic
      variceal ligation (EVL), other alternatives should be investigated. As APC
      provides coagulation at a shallow depth, it has been considered an ideal
      procedure to promote mucosal fibrosis for oesophageal varices. This study aims to
      investigate the safety and effectiveness of APC application to the oesophagus
      post-variceal obliteration in an attempt to decrease variceal recurrence and
      bleeding, as compared to EVL. PATIENTS AND METHODS: This study included 60
      patients with chronic liver disease and portal hypertension referred to the
      Gastrointestinal Endoscopy Unit, Kasr Al-Aini Hospital, Cairo University, during
      the period from August 2008 till January 2010. Patients had to have large-sized
      varices (F3), without history of bleeding, portal hypotensive drugs or
      intervention. Patients were allocated into either group I that included 30
      patients for whom EVL was performed and sequentially followed by one session of
      APC or group II that included 30 patients for whom EVL alone was done. Patients
      underwent surveillance endoscopy at 3 and 6months to evaluate variceal recurrence
      (F1 or more). RESULTS: Both groups were comparable in terms of the demographic
      features, hepatic functional reserve and endoscopic findings. Post-APC, fever was
      reported in 6.7%, dysphagia in 3.3%, procedure-related bleeding in 0% and
      stricture in 3.3%. At 3 and 6months follow-up, both groups were comparable in
      terms of variceal recurrence and none of the patients in both groups developed
      variceal bleeding. CONCLUSION: Although, APC application to the oesophageal
      mucosa is a safe technique, its additive benefit in terms of variceal recurrence
      and re-bleeding is comparable to EVL alone. This is encountered when only a
      single session of APC is applied. A more beneficial effect of multiple sessions
      of APC awaits further studies.

PMID- 23122454
TI  - Does bloody aspirate reflect the state of upper gastrointestinal mucosa in a
      critically ill newborn?
AB  - BACKGROUND AND STUDY AIMS: Critically ill newborns have many risk factors to
      develop stress related mucosal lesions (SRML). We used upper endoscopy to
      evaluate the presence of SRML in these neonates, to know the specificity and
      sensitivity of the bloody gastric aspirate to detect SRML and to identify the
      risk factors associated with the presence of SRML and bloody gastric aspirate.
      PATIENTS AND METHODS: This is a cross-sectional study done on 100 critically ill
      newborn after becoming clinically stable. SRML were diagnosed if there is
      hyperaemia, erosions or ulcers in the oesophagus, stomach, and/or the duodenum.
      RESULTS: SRML were found in 77% of neonates in the NICU though frank bloody
      aspirate was detected in only 22% of neonates. The presence of bloody aspirate
      showed low sensitivity (24.68%) and high specificity (86.96%) for the presence of
      SRML. The presence of bloody gastric aspirate showed a double fold risk for the
      presence SRML (OR=2.184, CI=0.584-8.171). Factors associated with SRML included
      respiratory distress (p=0.000, risk=4.006), the use of nasogastric tube (p=0.017,
      OR=3.281) and the use of triple antibiotics (p=0.001, risk=1.432). Factors
      associated with the presence of bloody gastric aspirate included the use of
      nasogastric tube (OR=1.629, p=0.000) and the presence of haemostatic disorders
      (OR=3.143, p=0.039). It was also associated with lower haemoglobin levels
      (p=0.000). CONCLUSION: SRML represents an under-diagnosed problem in NICUs.
      Absence of bloody gastric aspirate does not exclude the presence of SRML.

PMID- 23122455
TI  - Depressive mood and disease activity in inflammatory bowel disease.
AB  - BACKGROUND AND STUDY AIM: Some mood disorders are more prevalent in chronic
      medical conditions compared with the general population. The relationship between
      inflammatory bowel disease (IBD) and psychiatric disorders has been raised as an
      area of interest for investigation. In this study, we aimed to assess the
      probable relationship between depression and disease activity in IBD patients in
      Golestan province, northeast of Iran. PATIENTS AND METHODS: During February 2008
      to February 2010, 50 patients recently diagnosed as IBD cases attended the
      Golestan Research Center of Gastroenterology and Hepatology (GRCGH), northeast of
      Iran. The Simple Clinical Colitis Activity Index (SCCAI) was used to evaluate the
      disease activity. The Beck Depression Inventory (BDI) was used to assess the
      severity of depressive symptoms. Depression was assumed when the BDI score was 13
      points or higher. RESULTS: Sixteen cases (32%) had depressive characteristics.
      SCCAI and the Beck score were not significantly different between the two sexes.
      There was a non-significant correlation between SCCAI, Beck score, age and body
      mass index (BMI). CONCLUSIONS: We reported a relatively high percent of
      depression in IBD patients, although no significant relationship was seen.

PMID- 23122456
TI  - Renal failure after upper-gastrointestinal bleeding among cirrhotic patients in
      Upper Egypt.
AB  - BACKGROUND AND STUDY AIMS: Renal dysfunction is a common and serious problem in
      patients with advanced liver disease. The study aims to assess the incidence,
      risk factors and short-term prognosis of renal failure after upper
      gastrointestinal bleeding among cirrhotic patients in Upper Egypt. METHODS: We
      recruited 159 cirrhotic patients with 168 episodes of upper-gastrointestinal
      bleeding from Tropical Medicine and Gastroenterology Department, Assiut
      University Hospital. For all participants, the following were conducted: clinical
      evaluation, abdominal ultrasonography (US) examination, laboratory investigations
      and upper endoscopy. Risk factors of renal failure were identified using
      univariate, then multivariate analysis. RESULTS: The incidence of renal failure
      among bleeding episodes was 28%. Higher risk of renal failure among cirrhotic
      patients with upper-gastrointestinal bleeding was observed with shock (odds ratio
      (OR) 0.171, 95% confidence interval (CI) 0.047:0.624), bacterial infection (OR
      0.310, 95% CI 107:897), Child-Pugh class C (OR 2.79, 95% CI 1.018:7.62), higher
      serum bilirubin (OR 0.122, 95% CI 0.000:0.002), lower serum albumin (OR -0.188,
      95% CI -0.288:-0.056) and raised baseline blood urea (OR 0.181, 95% CI
      0.003:0.017) and serum creatinine (OR 0.533, 95% CI 0.002:0.004). Mortality among
      patients with renal failure was 31.9%. CONCLUSION: Renal failure is a frequent
      event among cirrhotic patients with upper-gastrointestinal bleeding and there are
      many contributing factors for its development. Mortality is relatively high among
      patients with renal failure in cirrhotics with upper-gastrointestinal bleeding.

PMID- 23122457
TI  - Appropriate use and diagnostic yield of upper gastrointestinal endoscopy in a
      tertiary referral hospital.
AB  - BACKGROUND AND STUDY AIMS: This is a prospective, descriptive, hospital-based
      study to evaluate the appropriateness and diagnostic yield of upper
      gastrointestinal (GI) tract endoscopy referrals to Soba University Hospital
      endoscopy unit using the American Society for Gastrointestinal Endoscopy
      guidelines for appropriate use of endoscopy. PATIENTS AND METHODS: All patients
      referred to Soba University Hospital for upper GI endoscopy during the study
      period were enrolled in the study after giving an informed consent. Statistical
      analysis was done using the Statistical Package for Social Sciences (SPSS)
      program to calculate frequencies and the X(2) test; P value was taken as
      significant at a level of less than 0.05. RESULTS: Overall, 220 patients were
      prospectively enrolled in the study, of which 126 (57%) were males, with a mean
      age of 46.5 +/- 17.9 years. A total of 190 patients (86%) were appropriately
      referred and the overall diagnostic yield was 46.8%. Those with appropriate
      referral had a higher diagnostic yield (50%) when compared to those with
      inappropriate referral (23%). CONCLUSION: The diagnostic yield of upper GI
      endoscopy was higher when patients were referred appropriately indicating that
      detection of relevant finding is greatly enhanced by the utilisation of standard
      guidelines.

PMID- 23122458
TI  - A rare complication in an adult patient after Kasai portoenterostomy for biliary
      atresia.
AB  - Kasai portoenterostomy has significantly prolonged the survival of patients with
      biliary atresia not undergoing liver transplantation. However, patients develop
      complications at some point during their life. The development of hepatocellular
      carcinoma is a very rare complication and has never been reported till date in
      the adult population. We report a case of development of hepatocellular carcinoma
      in a patient who had the Kasai procedure done for biliary atresia. It can pose a
      diagnostic and therapeutic challenge to physicians and delay in diagnosis is
      common in such patients, which can lead to grave consequences. We suggest that
      strict recommendations be made to avoid delays in the diagnosis of hepatocellular
      carcinoma, by intensifying screening in this group of patients by optimum use of
      magnetic resonance imaging (MRI).

PMID- 23122459
TI  - Gallbladder adenomyomatosis with tubercular portal lymphadenopathy masquerading
      as gallbladder carcinoma.
AB  - Gallbladder carcinoma is more likely to occur in elderly females and the presence
      of periportal adenopathy often signifies advanced disease. Such patients are
      generally not taken up for surgery and are treated palliatively. Isolated
      periportal tuberculosis without the evidence of disease elsewhere is in itself a
      rarity. Here we present a case study of gallbladder mass suspected of being
      gallbladder carcinoma with portal lymphatic metastasis actually turning out to be
      that of gallbladder adenomyoma with periportal tuberculosis. This case
      illustrates how mass lesions of the gallbladder are commonly and falsely
      interpreted to be malignant.

PMID- 23122460
TI  - Jejunal GIST causing acute massive gastrointestinal bleeding: role of
      multidetector row helical CT in the preoperative diagnosis and management.
AB  - In this report, we describe a 34-year-old man with a jejunal gastrointestinal
      stromal tumour (GIST) accompanied by an unusual severe haemorrhage. Because
      oesophagogastroduodenoscopy proved inconclusive in determining the source of the
      bleeding and also because of gradually dropping haemoglobin levels and
      persistence of the melena not allowing colonic preparation, colonoscopy was
      cancelled and a mesenteric angio-computed tomography (angio-CT) was deemed
      necessary. The results of this analysis showed a 5-cm heterogeneous mass located
      in the jejunal loop surrounded by abnormal arterial structures. This
      multidetector computed tomography (MDCT) appearance was highly suggestive of
      GIST. The patient then underwent an urgent laparotomy and, peroperative findings
      being compatible with angio-CT descriptions, a small-bowel resection was
      performed. The results of the histopathological examination confirmed the
      diagnosis of GIST. Angio-CT helps define the size of GIST as well as its range
      and location and can be used as the primary routine test for patients suffering
      from lower-GI bleeding.

PMID- 23122461
TI  - Giant gastric ulcer penetrating into the pancreas.
AB  - A 57-year-old man developed haematemesis and was referred to our institution. His
      discomfort had begun 3 weeks earlier and localised to the upper abdomen.
      Abdominal CT showed a defect of gastric mucosa and gastric wall thickening.
      Oesophagogastroduodenoscopy showed that he had an active gastric ulcer, 40 mm in
      diameter, on the lesser curvature in the upper third of the corpus and the
      presence of a pancreatic body at the ulcer base, penetration to the pancreas.
      Open gastrectomy was performed with a preoperative diagnosis of localised
      peritonitis caused by penetration of the stomach into the pancreas.
      Histopathology of resected specimens showed a benign peptic ulcer, 40*40 mm in
      size, was found on the lesser curvature in the antrum, and this had penetrated
      through the pancreas. The most serious complications of PUD include haemorrhage,
      perforation, penetration, and gastric outlet obstruction. Approximately 7% of
      patients experience perforation, which occurs when an ulcer erodes through the
      wall and leaks air and digestive contents into the peritoneal cavity. Antral and
      duodenal ulcers can penetrate into the pancreas. We report a case of gastric
      ulcer penetrating into the pancreas.

PMID- 23122463
TI  - Questioning optical coherence tomography.

PMID- 23122464
TI  - Ganciclovir gel for cytomegalovirus keratouveitis.

PMID- 23122465
TI  - Dexamethasone implant in pediatric uveitis.

PMID- 23122466
TI  - Predictors of AMD treatment response.

PMID- 23122467
TI  - Voriconazole for Candida endophthalmitis.

PMID- 23122468
TI  - Surgeon cataract volume and endophthalmitis.

PMID- 23122469
TI  - Ciliary sulcus lens power.

PMID- 23122472
TI  - Contaminated intraocular lens solution.

PMID- 23122474
TI  - Ganciclovir for cytomegalovirus retinitis.

PMID- 23122476
TI  - Intraoperative ultrasonography AIDS plaque positioning.

PMID- 23122477
TI  - Space flight and disc edema.

PMID- 23122479
TI  - [Analysis of dementia patient mortality in a psychogeriatric unit].
AB  - AIM: To determine the characteristics of patients with dementia who died in a
      psychogeriatric unit, and to describe the conditions that led to their death.
      MATERIAL AND METHODS: Observational study of patients who died in the
      Psychogeriatric unit of Hospital de la Santa Creu de Vic during a three and a
      half year period. RESULTS: Of the 554 patients admitted during the study period,
      we recorded a mortality of 14.6% (81 patients). The analysis of those who died
      showed that 67.9% were women, with a mean age of 85.8 years, with the most
      frequent cause being Alzheimer type dementia (37%) and being in an advanced stage
      (CDR3, GDS 6-7) in 72.8% of cases. On admission the following characteristics
      were recorded: Mini Mental State Examination (MMSE) 9.5, Barthel Index (BI) prior
      to entry 50.1, BI on admission 17.4, and Neuropsychiatric Inventory (NPI) 31.4. A
      therapeutic limitation treatment was determined for 84% of patients on admission.
      From the analysis of the conditions that lead to death it was noted that: In
      74.1% of the patients the death was a direct result of a triggering event (the
      most frequent being respiratory infection), in 17.3% the death occurred by a
      gradual decline, with no clear precipitating factor, and in 8.6% of patients
      palliative sedation was required due to poorly controlled symptoms. CONCLUSIONS:
      Intercurrent problems were the most common factors related to the death of the
      patients. Most patients died in the stages prior to the established criteria for
      terminal dementia. In some cases patients may experience disorder behavior as a
      refractory symptom.

PMID- 23122480
TI  - [Genetics and Alzheimer's disease: a population at risk].
AB  - The high prevalence of Alzheimer's disease, along with the possibility of new
      approaches in diagnosis through the use of biomarkers of cerebrospinal fluid is
      shifting the focus to the elderly with dementia or at risk. In this sense it
      seems important to review the genetic aspects of the elderly with familial
      Alzheimer's disease as well as those at risk. The wide distribution of genetic
      studies associated with this condition may also be helpful. To the classical
      findings of the genes for amyloid, the presenilins and apolipoprotein E, we must
      add other genes recently implicated in the pathogenesis of the disease, among
      which are found the clusterin gene, encoding the phosphatidyl-inositol-binding
      clathrin assembly protein gene, and the receptor for the complement C3b protein.

PMID- 23122481
TI  - [Hemiballismus of vascular origin. Pharmacological and rehabilitation approach].

PMID- 23122482
TI  - [Baboon syndrome after exposure to mercurochrome during chickenpox].

PMID- 23122483
TI  - Towards an aetiological treatment of type 1 diabetes? New tools, new strategies.

PMID- 23122484
TI  - Pretreatment of Agave americana stalk for enzymatic saccharification.
AB  - Agave americana is one of commonly grown agave species but currently less
      valuable because its large flower stalk cannot be used for producing alcoholic
      beverage. In the present study, the stalk was pretreated with dilute acid (DA),
      sulfite (SPORL), and sodium hydroxide (NaOH) to preliminarily assess its
      potential as feedstock for bioethanol production. The changes of cell wall
      components during the pretreatments, enzymatic digestibility of the pretreated
      stalks, and the adsorption of cellulases on the substrates were investigated.
      Results indicated that the pretreatments significantly improved the enzymatic
      digestibility of the agave stalk. SPORL pretreatment gave higher substrate and
      sugar yields, while NaOH pretreated stalk had better digestibility under the
      investigated conditions. The better hydrolysability of NaOH-pretreated stalk was
      attributed to low lignin and hemicellulose content and high affinity to
      cellulases.

PMID- 23122485
TI  - Assessing psychological factors affecting medical conditions: comparison between
      different proposals.
AB  - OBJECTIVE: We compared the provisional Diagnostic and Statistical Manual of
      Mental Disorders, Fifth Edition (DSM-5) criteria for Somatic Symptom Disorders
      (SSD) and an alternative classification based on the Diagnostic Criteria for
      Psychosomatic Research (DCPR) as to prevalence and associations with dimensional
      measures of psychological distress and functioning in a population of medical
      patients. METHOD: Seventy consecutive outpatients with congestive heart failure
      were administered an ad hoc structured clinical interview for the identification
      of DSM-5 SSD, the section concerning hypochondriasis of the Structured Clinical
      Interview for DSM-IV, the Structured Interview for DCPR and Paykel's Clinical
      Interview for Depression. Subjects also completed the Symptom Questionnaire and
      the Psychosocial Index. Global assessment of functioning was performed with the
      DSM-IV Axis V. RESULTS: A diagnosis within DSM-5 SSD was found in 13 patients
      (18.5%): 61.5% of them were diagnosed with the Psychological Factors Affecting
      Medical Condition category. Twenty-nine patients (41.4%) were classified
      according to the DCPR-based proposal: illness denial, demoralization and
      irritable mood were the most frequent specifiers. The DCPR-based classification
      showed a greater number of significant associations with dimensional measures of
      psychological distress, global functioning and stress. CONCLUSION: Compared to
      DSM-5 SSD, the DCPR-based proposal was more sensitive in detecting psychological
      factors relevant to illness course and provided a better characterization of such
      factors. The DCPR-based proposal was also superior in identifying patients with
      increased psychological distress and poor psychosocial functioning.

PMID- 23122486
TI  - Psychiatric morbidity in chronic respiratory disorders in an Indian service using
      GMHAT/PC.
AB  - OBJECTIVE: The study aimed to assess psychiatric morbidity in stable chronic
      respiratory disorders and to examine the pattern of psychiatric illness in
      specific respiratory disorders in Northern India. METHODS: All consecutive
      patients with stable chronic respiratory illnesses who attended the respiratory
      disease clinic were recruited in the study. Their healthy attendants were
      interviewed as a control group. The research clinician, trained in the use of the
      Global Mental Health Assessment Tool, Primary Care Version (GMHAT/PC),
      interviewed all the participants. The respiratory consultant made the respiratory
      illness diagnosis. The data were analyzed comparing the patient and the control
      group by using relative risk and adjusted odds ratios. RESULTS: Of 391 patients
      with respiratory illness, 44.8% had a mental illness identified by GMHAT/PC
      interview compared with 24.3% of 177 attendants (controls). Anxiety (20.6%),
      depression (13.2%) and obsessive compulsive disorders (4.6%) were the most
      frequently identified mental disorders in the respiratory disease group. Chronic
      obstructive pulmonary disease and bronchial asthma when combined with rhinitis
      had a significantly higher prevalence of comorbid mental illness than those
      illnesses alone. CONCLUSION: Patients with chronic respiratory illness have high
      mental health comorbidity. Physicians and practitioners can be trained to
      identify mental illness using computer-assisted tools such as GMHAT/PC (which is
      easy to use by clinicians and well accepted by patients). A holistic approach of
      providing care to such patients may improve their overall outcome and quality of
      life.

PMID- 23122487
TI  - Psychosis revealing familial idiopathic basal ganglia calcification.
AB  - We describe the case of a 39-year-old woman presenting with auditory
      hallucinations and delusions responsive to antipsychotic drugs. Computerized
      tomography scans revealed basal ganglia calcifications in the proband and in her
      two asymptomatic parents. Extensive etiological clinicobiological assessment
      allowed us to exclude known causes of brain calcifications and diagnose familial
      idiopathic basal ganglia calcification (IBGC). Neurological symptoms associated
      with psychiatric symptoms are common in IBGC. Nevertheless, purely psychiatric
      presentations, as demonstrated by the present case, are possible. However, a
      fortuitous association between asymptomatic IBGC and schizophrenia cannot be
      ruled out. Only brain imaging, followed by an extensive etiological assessment,
      allows for diagnosis of this rare disorder. 

PMID- 23122489
TI  - Contracting, prompting and reinforcing substance use disorder continuing care.
AB  - The contracting, prompting and reinforcing (CPR) aftercare intervention has
      improved treatment adherence and outcomes in a number of clinical trials. In
      multisite randomized clinical trial 92 graduates of two intensive substance use
      disorder programs who received CPR were compared to 91 who received standard
      treatment (STX). The CPR group evidenced increased frequency of aftercare group
      therapy attendance and near significant findings suggested that more CPR than STX
      participants completed 3 months (76 vs. 64%), 6 months (48 vs. 35%), and 9 months
      (35 vs. 22%) of aftercare. However, the groups did not differ on the majority of
      attendance measures and had similar abstinence rates at the 3-month (67% CPR vs.
      71% STX), 6-month (52% CPR vs. 51% STX), and 12-month (the primary outcome
      measure; 48% CPR vs. 49% STX) follow-up points. Exploratory analyses suggest that
      CPR might be more effective among participants not required to attend aftercare.
      The incremental capital and labor cost of CPR compared to STX was $98.25 per
      participant.

PMID- 23122488
TI  - Taxometric analysis of DSM-IV and DSM-5 alcohol use disorders.
AB  - BACKGROUND: With preparations currently being made for the Diagnostic and
      Statistical Manual of Mental Disorders-5th Edition (DSM-5), one prominent issue
      to resolve is whether alcohol use disorders are better represented as discrete
      categorical entities or as a dimensional construct. The purpose of this study was
      to investigate the latent structure of DSM-4th edition (DSM-IV) and proposed DSM
      5 alcohol use disorders. METHODS: The study used the Wave 2 National
      Epidemiologic Survey on Alcohol and Related Conditions (NESARC) to conduct
      taxometric analyses of DSM-IV and DSM-5 alcohol use disorders defined by
      different thresholds to determine the taxonic or dimensional structure underlying
      the disorders. RESULTS: DSM-IV and DSM-5 alcohol abuse and dependence criteria
      with 3+ thresholds demonstrated a dimensional structure. Corresponding thresholds
      with 4+ criteria were clearly taxonic, as were thresholds defined by cut-offs of
      5+ and 6+ criteria. CONCLUSIONS: DSM-IV and DSM-5 alcohol use disorders
      demonstrated a hybrid taxonic-dimensional structure. That is, DSM-IV and DSM-5
      alcohol use disorders may be taxonically distinct compared to no disorder if
      defined by a threshold of 4 or more criteria. However, there may be dimensional
      variation remaining among non-problematic to subclinical cases. A careful and
      systematic program of structural research using taxometric and psychometric
      procedures is warranted.

PMID- 23122490
TI  - Autonomous learning in humanoid robotics through mental imagery.
AB  - In this paper we focus on modeling autonomous learning to improve performance of
      a humanoid robot through a modular artificial neural networks architecture. A
      model of a neural controller is presented, which allows a humanoid robot iCub to
      autonomously improve its sensorimotor skills. This is achieved by endowing the
      neural controller with a secondary neural system that, by exploiting the
      sensorimotor skills already acquired by the robot, is able to generate additional
      imaginary examples that can be used by the controller itself to improve the
      performance through a simulated mental training. Results and analysis presented
      in the paper provide evidence of the viability of the approach proposed and help
      to clarify the rational behind the chosen model and its implementation.

PMID- 23122491
TI  - Renal artery stenosis: prevalence of, risk factors for, and management of in
      stent stenosis.
AB  - Atherosclerotic renal artery stenosis is common and is associated with
      hypertension and chronic kidney disease. More frequent use of percutaneous renal
      artery stent placement for the treatment of renal artery stenosis during the past
      2 decades has increased the number of patients with implanted stents. In-stent
      stenosis is a serious problem, occurring more frequently than earlier reports
      suggest and potentially resulting in late complications. Currently, there are no
      guidelines covering the approach to restenosis after renal artery stent
      placement. This article reviews data on the prevalence of and risk factors for
      the development of in-stent stenosis and the clinical manifestations, evaluation,
      and treatment of in-stent stenosis and suggests a strategy for the management of
      patients after percutaneous renal artery stent placement.

PMID- 23122492
TI  - Association of cardiac valvular calcifications and C-reactive protein with
      cardiovascular mortality in incident hemodialysis patients: a Japanese cohort
      study.
AB  - BACKGROUND: Cardiac valve calcification is seen frequently in patients undergoing
      dialysis. Serum C-reactive protein (CRP) level also is reported to predict future
      cardiovascular events. We investigated the association among valve calcification,
      CRP level, and mortality in patients with end-stage renal disease who were just
      beginning hemodialysis (HD) therapy. STUDY DESIGN: Observational cohort. SETTING
      & PARTICIPANTS: 1,290 consecutive patients who just started HD therapy were
      enrolled and were followed up to 10 years. PREDICTOR: Patients were divided into
      3 groups according to number of calcified valves: those without valve
      calcification, those with calcification in a single (aortic or mitral) valve, and
      those with calcification in both valves. They also were divided into tertiles
      according to CRP level. OUTCOMES: Cardiovascular and all-cause mortality.
      MEASUREMENTS: Echocardiography and CRP measurement were performed within 1 month
      after beginning HD therapy. RESULTS: During follow-up (median, 51 months), 335
      (25.9%) patients died, including 156 (12.1%) of cardiovascular disease. The
      adjusted HR for cardiovascular mortality was 2.80 (95% CI, 1.63-4.81) for 2
      calcifications versus 0 (P < 0.001). Furthermore, the risk of cardiovascular
      mortality was 3.66-fold higher in patients with calcifications in both valves
      (highest tertile of CRP) compared with patients without valve calcification
      (lowest tertile of CRP; P < 0.001). LIMITATIONS: Precise medical treatments or
      therapeutic interventions were not evaluated. CONCLUSIONS: Valve calcification
      and elevated CRP levels were not only related to additively increased risk of
      mortality, but also improved the prediction of mortality in patients with end
      stage renal disease who had just begun HD therapy.

PMID- 23122493
TI  - KRAS mutations in lung cancer.
AB  - Epidermal growth factor receptor (EGFR) gene mutations and increased EGFR copy
      numbers have been associated with a favorable response to EGFR tyrosine kinase
      inhibitors (TKI) in patients with non-small-cell lung cancer (NSCLC), and several
      markers have been identified that predict response to treatment. Lung
      adenocarcinomas also harbor activating mutations in the downstream GTPase, v-Ki
      ras2 Kirsten rat sarcoma viral oncogene (KRAS), and mutations in EGFR and KRAS
      appear to be mutually exclusive. Even though KRAS mutations were identified in
      NSCLC tumors more than 20 years ago, we have only just begun to appreciate the
      clinical value of determining KRAS tumor status. Recent studies indicate that
      patients with mutant KRAS tumors fail to benefit from adjuvant chemotherapy and
      do not respond to EGFR inhibitors. There is a clear need for therapies
      specifically developed for patients with KRAS-mutant NSCLC. In this review, we
      summarize the clinical and pathologic characteristics of patients with NSCLC and
      with KRAS mutations, describe work that explores the predictive and prognostic
      influence of KRAS mutations, and provide an overview of the "synthetic lethal"
      interactions and current approaches to targeting KRAS-mutant NSCLC.

PMID- 23122494
TI  - Serum level of osteopontin as a prognostic factor in patients who underwent
      surgical resection for non-small-cell lung cancer.
AB  - BACKGROUND: OPN is a multifunctional glycophosphoprotein originally described as
      a secreted protein from malignant epithelial cells. This study focused on the
      clinical significance of preoperative serum level of OPN in NSCLC patients who
      underwent a complete resection. PATIENTS AND METHODS: The serum OPN level was
      assayed in 244 patients who underwent a complete resection of NSCLC by
      commercially available sandwich enzyme-linked immunosorbent assay kits. The
      patients were considered as a higher group, when the serum OPN levels exceeded
      81.3 ng/mL. RESULTS: The patients included 166 male and 78 female subjects. The
      histologic types included 172 adenocarcinomas, 49 squamous cell carcinomas, and
      23 other types of carcinoma. The serum level of OPN in male patients (92.6 ng/mL)
      was significantly higher than that of female patients (76.9 ng/mL). The OPN level
      of squamous cell carcinoma was significantly higher than that of adenocarcinoma.
      The OPN level was significantly elevated in patients with the pleural invasion or
      microvascular invasion than those without the invasion. The 5-year survival rate
      after surgery in the lower OPN group (82.0%) was a significant favorable
      prognosis than that in the higher OPN group (63.7%) (P < .0001). The 5-year
      survival rates in the lower OPN group at stage I NSCLC (88.1%) was significantly
      better than that in the higher OPN group (80.5%) (P = .0321). CONCLUSION: The
      preoperative serum OPN level was a useful predictor of an unfavorable prognosis,
      and it was found to be an independent prognostic determinant of outcome in
      patients who underwent surgery for NSCLC.

PMID- 23122495
TI  - Exploitation of vegetables and fruits through lactic acid fermentation.
AB  - Lactic acid fermentation represents the easiest and the most suitable way for
      increasing the daily consumption of fresh-like vegetables and fruits. Literature
      data are accumulating, and this review aims at describing the main features of
      the lactic acid bacteria to be used for fermentation. Lactic acid bacteria are a
      small part of the autochthonous microbiota of vegetables and fruits. The
      diversity of the microbiota markedly depends on the intrinsic and extrinsic
      parameters of the plant matrix. Notwithstanding the reliable value of the
      spontaneous fermentation to stabilize and preserve raw vegetables and fruits, a
      number of factors are in favour of using selected starters. Two main options may
      be pursued for the controlled lactic acid fermentation of vegetables and fruits:
      the use of commercial/allochthonous and the use of autochthonous starters.
      Several evidences were described in favour of the use of selected autochthonous
      starters, which are tailored for the specific plant matrix. Pro-technological,
      sensory and nutritional criteria for selecting starters were reported as well as
      several functional properties, which were recently ascribed to autochthonous
      lactic acid bacteria. The main features of the protocols used for the manufacture
      of traditional, emerging and innovative fermented vegetables and fruits were
      reviewed. Tailored lactic acid bacteria starters completely exploit the potential
      of vegetables and fruits, which enhances the hygiene, sensory, nutritional and
      shelf life properties.

PMID- 23122496
TI  - Array-based transcriptional analysis of Clostridium sporogenes UC9000 during
      germination, cell outgrowth and vegetative life.
AB  - The members of the genus Clostridium, including the spore-forming anaerobic
      bacteria, have a complex and strictly regulated life cycle, but very little is
      known about the genetic pathways involved in the different stages of their life
      cycle. Clostridium sporogenes, a Gram-positive bacterium usually involved in food
      spoilage and frequently isolated from late blowing cheese, is genetically
      indistinguishable from the proteolytic Clostridium botulinum. As the non
      neurotoxic counterpart, it is often used as an exemplar for the toxic subtypes.
      In this work, we performed a microscopic study combined with a custom array-based
      analysis of the C. sporogenes cycle, from dormant spores to the early stationary
      phase. We identified a total of 211 transcripts in spores, validating the
      hypothesis that mRNAs are abundant in spores and the pattern of mRNA expression
      is strikingly different from that present in growing cells. The spore transcripts
      included genes responsible for different life-sustaining functions, suggesting
      there was transcript entrapment or basic poly-functional gene activation for
      future steps. In addition, 3 h after the beginning of the germination process,
      20% of the total up-regulated genes were temporally expressed in germinating
      spores. The vegetative condition appeared to be more active in terms of gene
      transcription and protein synthesis than the spore, and genes coding for
      germination and sporulation factors seemed to be expressed at this point. These
      results suggest that spores are not silent entities, and a broader knowledge of
      the genetic pathways involved in the Clostridium life cycle could provide a
      better understanding of pathogenic clostridia types.

PMID- 23122497
TI  - Inactivation of Salmonella enterica serovar Typhimurium on fresh produce by cold
      atmospheric gas plasma technology.
AB  - Cold atmospheric gas plasma treatment (CAP) is an alternative approach for the
      decontamination of fresh and minimally processed food. In this study, the effects
      of growth phase, growth temperature and chemical treatment regime on the
      inactivation of Salmonella enterica serovar Typhimurium (S. Typhimurium) by
      Nitrogen CAP were examined. Furthermore, the efficacy of CAP treatment for
      decontaminating lettuce and strawberry surfaces and potato tissue inoculated with
      S. Typhimurium was evaluated. It was found that the rate of inactivation of S.
      Typhimurium was independent of the growth phase, growth temperature and chemical
      treatment regime. Under optimal conditions, a 2 min treatment resulted in a 2.71
      log-reduction of S. Typhimurium viability on membrane filters whereas a 15 min
      treatment was necessary to achieve 2.72, 1.76 and 0.94 log-reductions of
      viability on lettuce, strawberry and potato, respectively. We suggest that the
      differing efficiency of CAP treatment on the inactivation of S. Typhimurium on
      these different types of fresh foods is a consequence of their surface features.
      Scanning electron microscopy of the surface structures of contaminated samples of
      lettuce, strawberry and potato revealed topographical features whereby S.
      Typhimurium cells could be protected from the active species generated by plasma.

PMID- 23122498
TI  - Reduced growth of Listeria monocytogenes in two model cheese microcosms is not
      associated with individual microbial strains.
AB  - Two model antilisterial microbial communities consisting of two yeasts, two Gram
      positive and two Gram negative bacteria, and originating from Livarot cheese
      smear were previously designed. They were used in the present study to analyse
      the impact of microbial population dynamics on growth of Listeria monocytogenes
      in cheese microcosm. Specific culture media and PCR primers were developed for
      simultaneous culture-dependent and real-time PCR quantification of strains
      belonging to Marinomonas sp., Paenibacillus sp., Staphylococcus equorum,
      Arthrobacter arilaitensis, Pseudomonas putida, Serratia liquefaciens, Candida
      natalensis, and Geotrichum candidum, in cheese microcosms. All strains were
      enumerated after 3, 5, 8 and 14 days at 15  degrees C. They established well at
      high counts in all cheese microcosms. Growth dynamics for all strains in presence
      of L. monocytogenes WSLC 1685 were compared to those of microbial communities
      obtained by omitting in turn one of the six members of the initial community. The
      growth of the microbial strains was neither markedly disturbed by Listeria
      presence nor by the removal of each strain in turn. Furthermore, these
      communities had a significant reducing effect on growth of L. monocytogenes
      independently of pH, as confirmed by mathematical modelling. A barrier effect was
      observed, that could be explained by specific competition for nutrients.

PMID- 23122499
TI  - Induction of bacteriocin production by coculture is widespread among plantaricin
      producing Lactobacillus plantarum strains with different regulatory operons.
AB  - We describe the bacteriocin-production phenotype in a group of eight singular
      bacteriocinogenic Lactobacillus plantarum strains with three distinct genotypes
      regarding the plantaricin locus. Genotyping of these strains revealed the
      existence of two different plantaricin-production regulatory operons, plNC8
      plNC8HK-plnD or plnABCD, involving three-component systems controlled each of
      them by a specific autoinducer peptide (AIP), i.e. PLNC8IF or PlnA. While all of
      the strains produced antimicrobial activity when growing on solid medium, most of
      them halted this production when cultured in broth, thus reflecting the
      functionality of regulatory mechanisms. Antimicrobial activity in broth cultures
      was re-established or enhanced when the specific AIP was added to the culture or
      by coculturing with specific bacterial strains. The latter trait appeared to be
      widespread in bacteriocinogenic L. plantarum strains independently of the
      regulatory system used to regulate bacteriocin production or the specific
      bacteriocins produced. The induction spectrum through coculture, i.e. the pattern
      of bacterial strains able to induce bacteriocin production, was characteristic of
      each individual L. plantarum strain. Also, the ability of some bacteria to induce
      bacteriocin production in L. plantarum by coculture appeared to be strain
      specific. The fact that induction of bacteriocin production by coculturing
      appeared to be a common feature in L. plantarum can be exploited accordingly to
      enhance the viability of this species in food and feed fermentations, as well as
      to contribute to probiotic functionality when colonising the gastrointestinal
      tract.

PMID- 23122500
TI  - Fast identification of wine related lactic acid bacteria by multiplex PCR.
AB  - The microflora of must and wine consists of yeasts, acetic acid bacteria and
      lactic acid bacteria (LAB). The latter group plays an important role for wine
      quality. The malolactic fermentation carried out by LAB leads to deacidification
      and stabilisation of wines. Nevertheless, LAB are often associated with wine
      spoilage. They are mainly responsible for the formation of biogenic amines.
      Furthermore, some strains produce exopolysaccharide slimes, acetic acid, diacetyl
      and other off-flavours. In this context a better monitoring of the vinification
      process is crucial to improve wine quality. Moreover, a lot of biodiversity
      studies would also profit from a fast and reliable identification method. In this
      study, we propose a species-specific multiplex PCR system for a rapid and
      simultaneous detection of 13 LAB species, frequently occurring in must or wine:
      Lactobacillus brevis, Lb. buchneri, Lb. curvatus, Lb. hilgardii, Lb. plantarum,
      Leuconostoc mesenteroides, Oenococcus oeni, Pediococcus acidilactici, P.
      damnosus, P. inopinatus, P. parvulus, P. pentosaceus and Weissella
      paramesenteroides.

PMID- 23122501
TI  - The susceptibility of Streptococcus thermophilus 14085 to organic acid, simulated
      gastric juice, bile salt and disinfectant as influenced by cold shock treatment.
AB  - Streptococcus thermophilus is a thermophilic lactic acid bacterium which is used
      as the starter organism for the fermentation of yoghurt and some cheese. In the
      present study, S. thermophilus BCRC 14085 was subjected to cold shock treatment
      by exposure at 10  degrees C for 2 h. The effect of cold shock on the
      susceptibility of S. thermophilus in subsequent lethal stress environments such
      as simulated gastric juice (pH 2.0-3.0), bile solution (2.0%) and various organic
      acids (0.75 M, pH 3.5) including propionic, lactic, acetic, citric and tartaric
      acid was investigated. In addition, the survival of cold-shocked and non-shocked
      S. thermophilus exposed to disinfectants, Clidox-S and Quatricide, were compared.
      Results revealed that cold shock enhanced the tolerance of S. thermophilus in the
      presence of simulated gastric juice (pH 2.5 and 2.8), while in bile solution, the
      population increase of cold-shocked cells is higher than that of non-shocked
      cells after 12 h of incubation. Furthermore, the susceptibility of S.
      thermophilus, regardless of cold shock, to organic acid varied with the kinds of
      organic acid examined. The cold-shocked S. thermophilus showed a significantly
      less survival (P < 0.05) than that of the non-shocked cells when exposed to
      lactic or acetic acid. Furthermore, cold shock reduced the survival of S.
      thermophilus when exposed to Quatricide but not Clidox-S.

PMID- 23122502
TI  - Technological and safety characteristics of Staphylococcaceae isolated from
      Spanish traditional dry-cured sausages.
AB  - The aim of this study was to determine the technological properties (nitrate
      reductase, proteolytic and lipolytic activities; and the ability to grow at the
      temperature and pH values of fermenting sausage, and at high NaCl concentrations)
      and safety characteristics (amino acid decarboxylase and enterotoxigenic
      activities) of 38 strains of Staphylococcaceae (11 of Staphylococcus epidermidis,
      15 of Staphylococcus equorum, 5 of Staphylococcus pasteuri and 7 of
      Staphylococcus saprophyticus) isolated from Androlla and Botillo, two Spanish
      traditional sausages, in order to evaluate their suitability as potential starter
      cultures in the manufacture of these sausages. Most strains were able to grow at
      10  degrees C, in the presence of 10% and 15% NaCl and at pH values of 5.5 and
      5.0, except for S. equorum strains, growth of which was reduced at these pH
      values. The proteolytic activity assessed by the agar plate method showed that
      89.5% and 52.6% of the strains were able to hydrolyze sarcoplasmic and
      myofibrillar proteins, respectively. These results were not confirmed by
      electrophoretic assays as only 47.2% of the strains changed the SDS-PAGE profile
      of actin, myosin and/or sarcoplasmic protein extracts. The assessment of the
      lipolytic activity by titration showed that only 21.0% of the strains can
      hydrolyze pork fat to any extent; whereas the profiles of the freed fatty acids
      were different in the different strains. Most of the strains showed decarboxylase
      activity against histidine, lysine, ornithine and tyrosine, but the quantities of
      biogenic amines produced were in most cases <25 ppm and <5 ppm for putrescine and
      cadaverine, respectively. Only four strains (10.5%), of S. epidermidis, produced
      enterotoxin C.

PMID- 23122503
TI  - Variation of cardinal growth parameters and growth limits according to
      phylogenetic affiliation in the Bacillus cereus Group. Consequences for risk
      assessment.
AB  - The growth rates of strains covering the seven major phylogenetic groups of
      Bacillus cereus sensu lato (as defined by Guinebretiere et al., 2008) at a range
      of temperature (7  degrees C-55  degrees C), pH (4.6-7.5) and a(w) (0.929-0.996,
      with 0.5%-10% NaCl as humectant) were determined. Growth rates were fitted by non
      linear regression to determine the cardinal parameters T(min), T(opt), T(max),
      pH(min), pH(opt), a(wmin) and MU(opt). We showed that cardinal parameters
      reflected the differences in the temperature adaptation observed between B.
      cereus phylogenetic groups I to VII. The ability of growing at low pH (up to 4.3)
      or low a(w) (from a(w) 0.929 and up to 10% NaCl) varied among strains. The
      strains of groups III and VII, the most tolerant to heat, were also the most
      adapted to high NaCl (all strains growing at 8% NaCl) and the ones of groups I
      and VI the least adapted (no growth at 7% NaCl). All strains of groups II and VII
      were able to grow at pH 4.6, and only a few strains of group VI. Phenotypic
      differences between the two psychrotrophic groups II and VI were revealed by
      contrasted acid and salt tolerance. The cardinal values determined in this work
      were validated by comparing with cardinal parameters of a panel of strains
      published elsewhere and with predictions of growth in a range of foods.

PMID- 23122504
TI  - Monitoring the bacterial population dynamics during the ripening of Galician
      chorizo, a traditional dry fermented Spanish sausage.
AB  - The dynamics of the bacterial population throughout the ripening of Galician
      chorizo, a traditional dry fermented sausage produced in the north-west of Spain,
      were investigated by using classical and molecular approaches. Fermented sausages
      are certainly complex matrices with PCR inhibitors and background microbiota.
      Therefore, two different DNA preparation methods were performed to elaborate each
      standard curve and no significant differences were found, showing a very good
      correlation between both methods (R(2)>0.994). The combination of the results
      obtained from microbial counts, species and genus-specific PCR as well as real
      time quantitative PCR (qPCR) allowed the identification for the dominant
      bacterial species and the study of the variation in the community composition
      over the ripening period. According to the data obtained both by identification
      of plate isolates and by real-time PCR, the dominant species among staphylococci
      and lactobacilli were Staphylococcus equorum and Lactobacillus sakei,
      respectively. However, only real-time PCR assay showed enough sensitivity to
      detect and quantify staphylococci in meat batter before stuffing, showing values
      of 5.28logCFU/g when quantifying Staphylococcus spp. and 2.87logCFU/g when
      quantifying S. equorum. In conclusion, real-time PCR was shown to be an efficient
      tool for the study of the complex associations developed in meat fermentations
      and for the characterization of dominant populations.

PMID- 23122505
TI  - Indigenous and spoilage microbiota of farmed sea bream stored in ice identified
      by phenotypic and 16S rRNA gene analysis.
AB  - Investigation of the initial and spoilage microbial diversity of iced stored sea
      bream was carried out. Culture dependent methods were used for bacterial
      enumeration and phenotypic identification of bacterial isolates, while culture
      independent methods, using bacterial 16S rRNA gene amplification, cloning and
      sequencing of DNA extracted directly from the flesh were also employed. The
      culture dependent approach revealed that the initial microbiota was dominated by
      Acinetobacter, Shewanella, Pseudomonas and Flavobacterium, while at the end of
      shelf-life determined by sensory analysis (16 days), the predominant microbiota
      was Pseudomonas and Shewanella. Culture independent approach showed that
      initially the sea bream flesh was strongly dominated by Acinetobacter, while
      Pseudomonas, Aeromonas salmonicida and Shewanella were the predominant phylotypes
      at the end of shelf-life. Initial and spoilage microbiota comprised of phylotypes
      previously identified by others using traditional or molecular techniques.
      However, Aeromonas has not been reported as part of the dominant microbiota of
      sea bream at the time of spoilage. Combination of classical and molecular
      methodologies better reveals the microbiota during storage by revealing bacteria
      that escape standard approaches and, thus, provides valuable complementary
      information regarding microbiological spoilage.

PMID- 23122506
TI  - High-salt brines compromise autoinducer-mediated bacteriocinogenic Lactobacillus
      plantarum survival in Spanish-style green olive fermentations.
AB  - The effect of NaCl on plantaricin production by five Lactobacillus plantarum
      strains was investigated. Plantaricin production in these strains was found to be
      regulated by three-component regulatory systems ruled by two different
      autoinducer peptides (AIPs), either PLNC8IF or Plantaricin A. Bacteriocin
      activity exhibited by these strains came to a halt in liquid medium containing
      NaCl concentrations of or above 2%. In contrast, bacteriocin activity was still
      observed when the producing strains were growing on solid medium containing up to
      4% NaCl. Bacteriocin activity in liquid medium containing up to 2% NaCl could be
      restored by coculturing the producing strains with a selected plantaricin
      production inducing strain of Lactococcus lactis. Growth of these
      bacteriocinogenic L. plantarum strains was monitored in traditional Spanish-style
      green olive fermentations. Survival of these strains could not be enhanced when
      provided with a range of plantaricin-production inducing mechanisms previously
      described, such as constitutive AIP production or coinoculation with a specific
      bacteriocin-production inducing strain of L. lactis. Our results suggest that it
      is advisable the use of constitutive bacteriocin producers, or at least non-AIP
      dependant ones, as starters for olive fermentations due to the intrinsic physical
      characteristics of this food fermentation, especially the high salt concentration
      of the brines currently used.

PMID- 23122508
TI  - Effect of ethanol and low pH on citrulline and ornithine excretion and arc gene
      expression by strains of Lactobacillus brevis and Pediococcus pentosaceus.
AB  - The accumulation of citrulline and ornithine in wine or beer as a result of the
      arginine catabolism of some lactic acid bacteria (LAB) species increases the risk
      of ethyl carbamate and putrescine formation, respectively. Several LAB species,
      which are found as spoilage bacteria in alcoholic beverages, have been reported
      to be arginine degrading. This study evaluates the effect of ethanol content and
      low pH on the excretion of citrulline and ornithine by two strains belonging to
      the potential contaminant species Lactobacillus brevis and Pediococcus
      pentosaceus. In the conditions that most affected cell viability, arginine
      consumption per cell increased noticeably, indicating that arginine utilization
      may be a stress responsive mechanism. L. brevis showed a higher accumulation of
      ornithine in the media than P. pentosaceus. In the presence of ethanol, a higher
      expression of the arcC gene was found in P. pentosaceus, which resulted in a
      lower excretion of citrulline and ornithine than in L. brevis. This suggests that
      L. brevis is more likely to produce these amino acids, which are precursors of
      ethyl carbamate and putrescine.

PMID- 23122509
TI  - High-cell-density fermentation of Saccharomyces cerevisiae for the optimisation
      of mead production.
AB  - Mead is a traditional drink that contains 8%-18% (v/v) of ethanol, resulting from
      the alcoholic fermentation of diluted honey by yeasts. Mead fermentation is a
      time-consuming process and the quality of the final product is highly variable.
      Therefore, the present investigation had two main objectives: first, to determine
      the adequate inoculum size of two commercial wine-making strains of Saccharomyces
      cerevisiae for the optimisation of mead fermentation; and second, to determine if
      an increase in yeast pitching rates in batch fermentations altered the resulting
      aroma profiles. Minor differences were detected in the growth kinetics between
      the two strains at the lowest pitching rate. With increasing pitching rates net
      growth of the strain ICV D47 progressively decreased, whereas for the QA23 the
      increasing inoculum size had no influence on its net growth. The time required to
      reach the same stage of fermentation ranged from 24 to 96 h depending on the
      inoculum size. The final aroma composition was dependent on the yeast strain and
      inoculum size. Fourteen of the twenty-seven volatile compounds quantified could
      contribute to mead aroma and flavour because their concentrations rose above
      their respective thresholds. The formation of these compounds was particularly
      pronounced at low pitching rates, except in mead fermented by strain ICV D47, at
      10(6) CFUs/mL. The esters isoamyl acetate, ethyl octanoate and ethyl hexanoate
      were the major powerful odourants found in the meads. The results obtained in
      this study demonstrate that yeast strain and inoculum size can favourably impact
      mead's flavour and aroma profiles.

PMID- 23122510
TI  - Macedovicin, the second food-grade lantibiotic produced by Streptococcus
      macedonicus ACA-DC 198.
AB  - Streptococcus macedonicus ACA-DC 198 was found to produce a second lantibiotic
      named macedovicin in addition to macedocin. Macedovicin was purified to
      homogeneity and mass spectrometric analysis identified a peptide of approximately
      3.4 kDa. Partial N-terminal sequence analysis and tandem mass spectrometry
      revealed that macedovicin was identical to bovicin HJ50 and thermophilin 1277
      produced by Streptococcus bovis and Streptococcus thermophilus, respectively.
      Macedovicin inhibits a broad spectrum of lactic acid bacteria, several food
      spoilage species (e.g. Clostridium spp.) and oral streptococci. We determined the
      complete biosynthetic gene cluster of macedovicin. Even though the gene clusters
      of macedovicin, thermophilin 1277 and bovicin HJ50 were almost identical at the
      nucleotide level, there were important differences in their predicted genes and
      proteins. Bovicin HJ50-like lantibiotics were also found to be encoded by
      Streptococcus suis strains SC84 and D12, Enterococcus columbae PLCH2, Clostridium
      perfringens JGS1721 and several Bacillus strains. All these lantibiotics
      contained a number of conserved amino acids that may be important for their
      biosynthesis and activity, while phylogenetic analysis supported their dispersion
      by horizontal gene transfer. In conclusion, the production of multiple
      bacteriocins may enhance the bio-protective potential of S. macedonicus during
      food fermentation.

PMID- 23122511
TI  - Chronic repetitive nonprogressive epilepsia partialis continua due to rheumatoid
      meningitis.

PMID- 23122507
TI  - Effects of pectinolytic yeast on the microbial composition and spoilage of olive
      fermentations.
AB  - This study resulted in the identification of pectinolytic yeasts in directly
      brined Sicilian-style green olive fermentations and examination of the influence
      of those yeasts on the microbial composition and quality of fermented olives.
      Firstly, defective olives processed in Northern California from 2007 to 2008 and
      characterized by high levels of mesocarp tissue degradation were found to contain
      distinct yeast and bacterial populations according to DNA sequence-based
      analyses. Strains of (pectinolytic) Saccharomyces cerevisiae, Pichia manshurica,
      Pichia kudriavzevii, and Candida boidinii isolated from directly brined olives
      were then inoculated into laboratory-scale olive fermentations to quantify the
      effects of individual yeast strains on the olives. The pH, titratable acidity,
      and numbers of lactic acid bacteria (LAB) and yeasts varied between the
      fermentations and fermentations inoculated with P. kudriavzevii and C. boidinii
      promoted the development of LAB populations. Olive tissue structural integrity
      declined significantly within 30, 74, and 192 days after the inoculation of
      pectinolytic S. cerevisiae, P. manshurica and C. boidinii, respectively. In
      comparison, tissue integrity of olives in control fermentations remained intact
      although pectinolytic yeasts were present. Notably, pectinolytic yeasts were not
      found in fermentations inoculated with (non-pectinolytic) P. kudriavzevii and
      olives exposed to a 1:1 ratio of P. kudriavzevii and P. manshurica exhibited no
      significant tissue defects. This study showed that pectinolytic yeast are
      important components of directly brined green olive fermentations and damage
      caused by pectinolytic yeasts might be prevented by other microbial colonists of
      the olives.

PMID- 23122512
TI  - Effects of an educational program on self-management in patients with epilepsy.
AB  - PURPOSE: Self-management majorly determines the health status of patients with
      epilepsy because the most important strategies for controlling seizures include
      receiving and adhering to prescribed therapies, and making appropriate lifestyle
      adjustments. Patients with epilepsy have various educational needs and must adopt
      many self-management behaviors to control their condition. This study was a
      clinical trial that evaluated the effects of an educational program on self
      management in patients with epilepsy. METHODS: Participants (n=60) were recruited
      from the Neurology Clinic in Zanjan, Iran. Patients were randomly assigned to the
      intervention and control groups (n=30 in each). The intervention group received
      four educational sessions on epilepsy, including a self-management plan. All
      participants completed the Epilepsy Self-Management Scale before the intervention
      and 1 month post-intervention. The chi-square test, Fisher's exact test,
      independent t-test, and paired samples t-test were used to compare the groups.
      RESULTS: At baseline, demographic characteristics and self-management scores did
      not differ significantly. One month after the intervention, self-management
      scores differed significantly (p<0.001) between the two groups. CONCLUSION: The
      educational program had beneficial effects on self-management behaviors in
      patients with epilepsy.

PMID- 23122513
TI  - [Analysis of gene expression data regulated by clock-genes: methodological
      approach and optimization].
AB  - BACKGROUND: In microarray data, wide-scale correlations are numerous and increase
      the number of genes correlated to a test condition (phenotype, mutation status,
      etc.) either positively or negatively. Several methods have been developed to
      limit the effect of such correlations on the false discovery rate, but these may
      reject too many genes that have a mild or indirect impact on the studied
      condition. We propose here a simple methodology to correct this spurious effect
      without eliminating weak but true correlations. RESULTS: This methodology was
      applied to a microarray dataset designed to distinguish heterozygous BRCA1
      mutation carriers from non-carriers. As our samples were collected at different
      times in the morning, we evaluated the effect of correlations due to circadian
      rhythm. The circadian system is a well-known correlation network, regulated by a
      small number of period genes whose expression varies throughout the day in
      predictable ways. The downstream effects of this variation on the expression of
      other genes, however, are incompletely characterized. We used two different
      strategies to correct this correlation bias, by either dividing or multiplying
      the expression of correlated genes by the expression of the considered period
      gene according to the sign of the correlation between the period gene and
      correlated gene (respectively positive or negative). CONCLUSIONS: We observed a
      linear relationship between the number of false-positive/negative genes and the
      strength of the correlation of the candidate gene to the test condition. BRCA1
      was highly correlated to the period gene Per1; our correction methodology enabled
      us to recover genes coding for BRCA1-interacting proteins which were not selected
      in the initial direct analysis. This methodology may be valuable for other
      studies and can be applied very easily in case of well-known correlation
      networks.

PMID- 23122514
TI  - [Calcium - calcium intakes in chronic kidney disease: is there a consensus?].

PMID- 23122515
TI  - Work, family and daily mobility: a new approach to the problem through a mobility
      survey.
AB  - OBJECTIVES: To analyze gender inequalities in socioeconomic factors affecting the
      amount of time spent travelling for work-related and home-related reasons among
      working individuals aged between 30 and 44 years old during a weekday in
      Catalonia (Spain). METHODS: A cross-sectional study was conducted. Data were
      obtained from employed individuals aged between 30 and 44 years of age who
      reported travelling on the day prior to the interview in the Catalan Mobility
      Survey 2006 (N = 23,424). Multivariate logistic regression models were adjusted
      to determine the factors associated with longer time spent travelling according
      to the reason for travelling (work- or home-related journeys). Odds ratios and
      95% confidence intervals are presented. RESULTS: A higher proportion of men
      travelled and spent more time travelling for work-related reasons, while a higher
      proportion of women travelled and spend more time travelling for home-related
      reasons. A higher educational level was associated with greater time spent
      travelling for work-related reasons in both men and women but was related to an
      increase in travelling time for home-related reasons only in men. In women, a
      larger household was associated with greater travel time for home-related reasons
      and with less travel time for work-related reasons. CONCLUSION: This study
      confirms the different mobility patterns in men and women, related to their
      distinct positions in the occupational, family and domestic spheres. Gender
      inequalities in mobility within the working population are largely determined by
      the greater responsibility of women in the domestic and family sphere. This
      finding should be taken into account in the design of future transport policies.

PMID- 23122516
TI  - [Current dietary exposure to mercury during pregnancy and childhood, and public
      health recommendations].
AB  - Exposure to high levels of mercury during vulnerable periods (such as pregnancy
      and childhood) may have serious consequences for cognitive development, as
      observed after acute poisoning episodes in Japan and Irak. The main source of
      mercury exposure in the general population is consumption of certain types of
      fish. There is growing concern about the possible neurotoxic effects of mercury,
      especially in younger children in populations where fish intake is moderate to
      high. The scientific evidence to date is inconclusive. In Spain, the Childhood
      and Environment (Infancia y Medio Ambiente [INMA]) project has provided
      information on levels of prenatal exposure to mercury among 1800 newborns from
      Valencia, Sabadell, Asturias and Guipuzcoa. In general, levels were high, being
      above the World Health Organization's recommended dose in 24% of children and
      above the recommended levels of the U.S. Environmental Protection Agency in 64%.
      However, the results did not indicate a significant association between prenatal
      mercury exposure and delayed cognitive development during the second year of
      life. Various agencies have developed recommendations on fish consumption for
      pregnant women and children, due to the presence of mercury. These
      recommendations should be strengthened, since there is general consensus among
      all regional and national public administrations that fish is an essential source
      of nutrients for development in the early stages of life.

PMID- 23122517
TI  - [First French national survey on lifestyle and toxic factors in infertile
      couples].
AB  - OBJECTIVES: The purpose of our study is to assess, prior to any treatment for
      infertility, the environment and quality of life of candidate couples for
      medically assisted procreation (MAP) and the toxic factors which may be related
      to their difficulty in conceiving. PATIENTS AND METHODS: A screening
      questionnaire aimed at 796 patients (348 couples) has been collected by 43
      assisted reproductive techniques (ART) centers in France. Stress factors,
      anxiety, toxic and environmental factors have been recorded and analysed.
      RESULTS: Women were on average younger than men (34.9 y +/- 5.3 vs. 37.5 y +/-
      7.5), with a normal BMI, and 78% of them had no children. Sexual relations are
      regular: 2.14 per week. However, 1 in 8 women reports having sexual problems as
      opposed to 2 in 100 men (P < 0.0001), the most common problems being painful
      intercourse, insensitivity and bleeding. Fifty percent of the surveyed women say
      they have painful periods. Smoking and cannabis use were significantly higher in
      the men (32% vs. 20% and 6,4% vs. 1,2%). Alcohol consumption is more common in
      men (32 vs. 23%, P < 0.01). Stress related to infertility was significantly
      higher in the women (54% vs. 23%; P < 0.001). DISCUSSION AND CONCLUSION: This
      first prospective French survey has revealed an increased incidence of smoking
      and an escalation of sexual problems (decrease in sexual relations, dyspareunia)
      and dysmenorrhea in women. It has also revealed stress at work in couples, and
      increased stress levels due to infertility in the female partners participating
      in this study. Our study suggests that there are numerous toxic and environmental
      factors which are potentially harmful for a couple's fertility and which should
      be corrected before any MAP treatment is attempted in order to optimise the
      results in ART and to increase natural fertility.

PMID- 23122518
TI  - Unplanned reoperation rate as a measure for hospital quality.

PMID- 23122519
TI  - Detection of patients at high risk for non-occlusive mesenteric ischemia in
      hemodialysis.
AB  - BACKGROUND: Nonocclusive mesenteric ischemia (NOMI) is an emerging condition in
      hemodialysis (HD) patients not widely studied. MATERIALS AND METHODS: A
      retrospective study was conducted between 2003 and 2011. NOMI cases were
      recorded, and demographic, clinical, biochemical, and HD parameters were
      collected. This group was compared with a control group (n = 93). Risk factors,
      prognosis, and survival were analyzed. RESULTS: There were 57 episodes of NOMI
      (incidence, 2.29 episodes per 100 patients/y). Cecum was the most frequently
      affected segment. Nineteen patients (33%) underwent surgery. Twenty-six patients
      (59%) did not survive the acute episode. Cecal damage was the only protective
      factor associated with mortality (relative risk [RR], 0.712; P = 0.044). The
      incidence of NOMI was related to erythropoietin resistance index, diabetes
      mellitus, and longer time on HD compared with control group (RR, 6.92, P = 0.009;
      RR, 9.98, P = 0.005; and RR, 1.017, P < 0.001, respectively). Mortality in
      survival NOMI patients was higher at 4-y follow-up compared with that in the
      control group (log-rank, 15.5; P < 0.0001). CONCLUSIONS: NOMI is associated with
      erythropoietin resistance index, diabetes mellitus, and longer time on HD.
      Hypotension must be avoided in these high-risk patients to prevent NOMI.

PMID- 23122520
TI  - A woman with systemic lupus erythematosus and polyadenopathy.
AB  - We present the case of a 51 year old woman with a history of several years of non
      organ specific Systemic Lupus Erythematosus, who presented a toxic syndrome and
      adenopathy and cranial nerve affection. We carried out the differential
      diagnosis. We then described the case resolution and progression.

PMID- 23122521
TI  - Tocilizumab in a patient with tophaceous gout resistant to treatment.
AB  - Gout is a disease characterized by acute episodes of pain, which occurs as the
      result of monosodic urate crystal deposit in the joint and periarticular tissue.
      In some cases, gout behaves as a severe inflammatory arthopathy that is difficult
      to manage, generating structural joint damage and functional impairment. We
      report the case of a 44 years old man with gouty arthritis for 12 years, not
      responding to NSAIDs, alopurinol, colchicine or corticosteroids. Tocilizumab was
      started with favorable clinical and laboratory results after treatment.

PMID- 23122522
TI  - Discovery of di-indolinone as a novel scaffold for protein tyrosine phosphatase
      1B inhibitors.
AB  - A series of di-indolinone derivatives was designed and synthesized to optimize
      our lead compounds basing on molecular docking study as PTP1B inhibitors.
      Successive enzymatic assay identified the synthetic di-indolinone as novel PTP1B
      inhibitors with low micromole-ranged inhibitory activity and at least several
      fold selectivity over other tested homologous PTPs.

PMID- 23122523
TI  - Microwave-assisted synthesis, molecular docking and antitubercular activity of
      1,2,3,4-tetrahydropyrimidine-5-carbonitrile derivatives.
AB  - Based on bioisosteric similarities with isoniazid, a series of 1,2,3,4
      tetrahydropyrimidine-5-carbonitrile derivatives has been designed. The target
      compounds have been synthesized by multicomponent reaction which involves one-pot
      organic reactions using ethylcyanoacetate, urea/thiourea and arylaldehydes in
      presence of ethanolic K(2)CO(3). Two methodologies, conventional and microwave
      assisted, have been adopted for the synthesis. The later strategy gave high
      yields in less than 10 min as compared to long hours using the former approach.
      Molecular docking of the target compounds into the enzyme Mycobacterium
      tuberculosis enoyl reductase (InhA) revealed important structural information on
      the plausible binding interactions. Major binding interactions were found to be
      of dispersion type (residues Tyr158, Ile215, Met103 and Met199) and a hydrogen
      bond with Tyr158. Binding poses of the all the compounds were energetically
      favorable and showed good interactions with the active site residues. Few
      selected compounds were also evaluated for antitubercular activity in vitro
      against drug-sensitive M. tuberculosis H37Rv strain and clinically isolated S, H,
      R and E resistant M. tuberculosis by luciferase reporter phage (LRP) assay
      method. Some compounds displayed promising antimycobacterial activity comparable
      or less than the standard drugs isoniazid and rifampicin.

PMID- 23122524
TI  - Synthesis and biological evaluation of novel spin labeled 18beta-glycyrrhetinic
      acid derivatives.
AB  - Eighteen novel spin-labeled 18beta-glycyrrhetinic acid (GA) derivatives were
      designed, synthesized, and evaluated for cytotoxicity against four human tumor
      cell lines (A-549, DU-145, KB and KBvin). Most of the derivatives showed more
      significant cytotoxicity than that of the parent compound GA. The best compound,
      6j, with a tryptophan amino moiety and piperidine nitroxyl radical showed GI(50)
      values of 13.7-15.0 MUM, and was fivefold more potent than GA. In a mechanism of
      action study, compound 7a was confirmed as a 20S proteasome inhibitor in both in
      vitro and cell-based assays. These findings support further optimization efforts
      based on 18beta-GA as a lead compound to develop potential anticancer drug
      candidates.

PMID- 23122525
TI  - Fluorescent nitrile-based inhibitors of cysteine cathepsins.
AB  - Cysteine cathepsins play an important role in many (patho)physiological
      conditions. Among them, cathepsins L, S, K and B are subjects of several drug
      discovery programs. Besides their role as drug targets, cysteine cathepsins are
      additionally considered to be possible biomarkers for inflammation and cancer.
      Herein, we describe the design, synthesis, biological evaluation and spectral
      properties of fluorescently labeled dipeptide- and azadipeptide nitriles.

PMID- 23122526
TI  - Allele frequencies of 12 Y-chromosomal STRs in Chinese Tuvans in the Altay
      region.
AB  - Allele and haplotype frequencies of 12 Y-chromosomal short tandem repeats (STRs)
      included in the PowerPlex((r)) Y Systems (Promega) were determined in a sample of
      150 unrelated healthy male individuals of Chinese Tuvans living in the Altay
      region of Xinjiang Uygur Autonomous Region. Allele frequencies and gene diversity
      for each Y-STR locus were determined. The observed haplotype diversity value was
      0.9708. The present results can be used as Chinese Tuvan genetic information
      resources in routine population study and forensic analysis.

PMID- 23122527
TI  - Allele frequencies of 15 STRs in five ethnic groups (Han, Gelao, Jing, Shui and
      Zhuang) in South China.

PMID- 23122528
TI  - Quantitative Heel Ultrasound (QUS) measures of bone quality in association with
      mood and anxiety disorders.
AB  - BACKGROUND: The common mental disorders are potential risk factors for low bone
      mass as a result of disease and/or medication-related processes. Quantitative
      heel ultrasound (QUS) is a portable and relatively cheap screening tool for
      determining fracture risk. Thus, we investigated the association between QUS
      parameters, mood and anxiety disorders in a population-based sample of 745 men
      and 897 women. METHODS: Using a clinical interview (SCID-I/NP), mood and anxiety
      disorders were identified. Bone quality was established using QUS and included
      the following parameters: Broadband Ultrasound Attenuation (BUA), Speed of Sound
      (SOS) and Stiffness Index (SI). Anthropometry, socio-economic status (SES),
      medication use and lifestyle factors were determined. RESULTS: In men, mood and
      anxiety disorders were associated with lower age-weight- and smoking-adjusted
      SOS, BUA and SI. In women, age was an effect modifier. Among younger women (<=
      40yr), mood disorders were associated with lower age-weight- and smoking-adjusted
      SOS and SI but not BUA. No differences were detected in older women or women with
      anxiety disorders. These patterns persisted after adjustment for activity,
      alcohol, calcium intake, SES and medications. LIMITATIONS: Cross-sectional study
      design, and possible residual or unrecognised confounding. CONCLUSION: Our data
      suggest that bone quality, as measured by QUS, is reduced among men and younger
      women with a history of mood disorders. Furthermore, an inverse association
      between anxiety disorders and bone quality was evident for men. Thus, QUS may be
      a useful screening tool for determining fracture risk within these populations.

PMID- 23122529
TI  - The association between psychotic mania, psychotic depression and mixed affective
      episodes among 14,529 patients with bipolar disorder.
AB  - BACKGROUND: Psychotic and mixed affective episodes are prevalent in the course of
      bipolar disorder. Despite many studies on the implications of psychotic mania
      (PM), psychotic depression (PD) and mixed affective episodes (MAE), relatively
      little is known about the relationship between the three subtypes. The present
      study aimed to investigate whether the occurrence of PM, PD and MAE were
      associated with one another. METHODS: This is a nationwide register-based,
      historical prospective cohort study. Data was obtained from the Danish
      Psychiatric Central Research Register. Subjects were defined as all individuals
      assigned with an ICD-10 diagnosis of bipolar disorder between January 1st 1994
      and December 31st 2010. Potential associations among psychotic and mixed
      affective episodes were tested by means of logistic regression. RESULTS: We
      identified 14,529 individuals with bipolar disorder with lifetime incidences of
      PM, PD and MAE of 19%, 15% and 17% respectively. We detected significant
      associations between PM and MAE (Adjusted Odds Ratio (AOR)=1.26, p=0.003), PD and
      MAE (AOR=1.24, p=0.001), and PM and PD (AOR=1.28, p=0.005). LIMITATIONS:
      Diagnoses were assigned as part of routine clinical practice. CONCLUSIONS:
      According to this register-based study, PD, PM and MAE are all associated with
      one another. This knowledge should be taken into consideration by clinicians when
      monitoring patients with bipolar disorder and by nosologists when defining the
      criteria and potential subtypes for mixed affective episodes for the upcoming DSM
      5 and ICD-11.

PMID- 23122530
TI  - Clinical effects of electroconvulsive therapy in severe depression and
      concomitant changes in cerebral glucose metabolism--an exploratory study.
AB  - OBJECTIVE: Electroconvulsive therapy (ECT) is an effective mode of treatment-
      especially for severe depression and for depression refractory to
      pharmacotherapy, nevertheless the mode of action of ECT is far from being fully
      understood. This study assessed the effects of a series of ECT in depressive
      subjects on cerebral glucose metabolism measured by FDG-PET scans pre- and post
      therapy in thus far the largest group of 12 patients. METHODS: Our analysis
      included careful repeated evaluation of clinical changes in mood and behaviour by
      standardised questionnaires, which allowed testing for a potential correlation
      between clinical and cerebral metabolic changes. PET scanning was done within a
      predefined time window and we used predefined ROIs with counts normalized to the
      pons activity. RESULTS: We observed few changes in cerebral glucose metabolism
      over time. There was a marginal increase in the left temporal and a trend for a
      decrease in left frontobasal areas subsequent to treatment in our sample. FDG
      uptake patterns remained remarkably stable in all the other predefined ROIs pre-
      and post-treatment. There were no significant correlations between changes in
      relative metabolic rates and changes in depression scores and parameters derived
      from neurocognitive testing. CONCLUSIONS: Our study thus cannot support the view
      that FDG-PET can assess the functional brain changes that are likely to occur
      subsequent to ECT in such a scenario, but this may be related to limited
      sensitivity given the sample size. Future studies thus might wish to challenge
      this notion in larger patient samples to clarify this issue.

PMID- 23122531
TI  - [Cement burns: a 10-year retrospective study in our burn unit. About 55 cases].
AB  - SUBJECT: Although cement burns represents only a small percentage of admissions
      to burn centers, their diagnosis and treatment are specific. Our retrospective
      study concerns all patients treated for cement burns in our unit between 1999 and
      2009. This is the largest series described. PATIENTS AND METHOD: Fifty-five
      patients, aged from 23 to 63, were treated in our burn unit from 1999 to 2009. A
      review of medical and socioeconomic data was made from computer data files.
      RESULTS: This population is predominantly male, young and active. These burns
      occurred mainly in a domestic accident situation (78.2%). Burns were limited but
      deep and concerned especially lower limbs. The average duration of treatment was
      39days. Forty-four patients were treated medically. The mean duration of sick
      live for these patients was 63 days. It was only of 21 days for those treated
      surgically. Aesthetic and functional sequelae were present in 88% of medically
      treated patients and in 18% of patients treated surgically. CONCLUSION: This
      study demonstrates that early surgical diagnosis and the coverage (care) of these
      burns allows to limit the socioeconomic echo and to reduce the risk of after
      effects for this population of patients mainly young and active. The necessity of
      strengthening the precautionary measures with these users who are informed enough
      about the risks incurred during the misuse of the cement is also a reality.

PMID- 23122532
TI  - [Evaluation of the psychological benefits of breast augmentation for aesthetic
      purposes. Results of a multicenter prospective study of a series of 181
      patients].
AB  - BACKGROUND: Cosmetic breast augmentation is becoming increasingly popular and
      acceptable to women in France. This prospective and multicenter study aims to
      investigate whether breast augmentation surgery for aesthetic purposes leads to
      improved body image, self-esteem, depression problems and sexuality. We also
      sought to analyze the sociodemographic profile of woman who underwent this
      surgery. PATIENTS AND METHODS: This study was conducted in France, from March
      2009 to March 2011. One hundred and eighty-one patients were included in the
      survey. We used questionnaires to analyze body image, self-esteem, sexuality,
      depression, motivations and the sociodemographic profile of the patients before
      surgery and 6 months after. Questionnaires that were answered were returned in an
      anonymous way to the investigators to guarantee a blinded survey. RESULTS: The
      findings showed that women who underwent breast augmentation were mostly
      employed, married and aged between 20 and 30 years. Analyses revealed a
      significant improvement in body image, self-esteem and depressive symptoms, 6
      months after surgery. Correlations between body image and self-esteem and between
      depression and self-esteem were also demonstrated. Only sexuality was almost
      unchanged after the procedure. Finally, a change of body image induced by breast
      augmentation surgery would improve self-esteem and thus reduce the signs for a
      depression. CONCLUSION: As with any request for aesthetic surgery, the desire for
      morphological breast surgery must be analyzed accurately and requires very
      thorough questioning by the plastic surgeon. The expected result is not only
      morphological but also psychological, as outlined in our study. The goal of
      breast augmentation surgery is to create a physical result that matches the
      expected body image in order to improve the patient's body image and self-esteem
      and so, bring the patient to recognize herself. Under these conditions, cosmetic
      breast augmentation surgery will assume a therapeutic function.

PMID- 23122533
TI  - Autoimmunity and cystatin SA1 deficiency behind chronic mucocutaneous candidiasis
      in autoimmune polyendocrine syndrome type 1.
AB  - Patients with the monogenic disease autoimmune polyendocrine syndrome type I
      (APSI) develop autoimmunity against multiple endocrine organs and suffer from
      chronic mucocutaneous candidiasis (CMC), a paradoxical complication with an
      unknown mechanism. We report here that saliva from APSI patients with CMC is
      defective in inhibiting growth of Candida albicans in vitro and show reduced
      levels of a salivary protein identified as cystatin SA1. In contrast, APSI
      patients without CMC express salivary cystatin SA1 and can inhibit C. albicans to
      the same extent as healthy controls. We evaluated the anti-fungal activity of
      cystatin SA1 and found that synthesized full length cystatin SA1 efficiently
      inhibits growth of C. albicans in vitro. Moreover, APSI patients exhibit salivary
      IgA autoantibodies recognizing myosin-9, a protein expressed in the salivary
      glands, thus linking autoimmunity to cystatin SA1 deficiency and CMC. This data
      suggests an autoimmune mechanism behind CMC in APSI and provides rationale for
      evaluating cystatin SA1 in antifungal therapy.

PMID- 23122534
TI  - Clinical efficacy of 300IR 5-grass pollen sublingual tablet in a US study: the
      importance of allergen-specific serum IgE.
AB  - BACKGROUND: Previous trials have demonstrated the efficacy, safety, and optimal
      dosage of the 5-grass pollen sublingual tablet for adults and children with grass
      pollen-induced allergic rhinoconjunctivitis. OBJECTIVES: We sought to evaluate
      the efficacy and safety of 300 index of reactivity (IR) 5-grass pollen sublingual
      tablet in US adults. METHODS: Adults with grass pollen allergy and
      Rhinoconjunctivitis Total Symptom Scores of 12 or greater (scale, 0-18) during
      the previous grass pollen season were randomized in a double-blind, placebo
      controlled study to receive 300IR 5-grass pollen sublingual tablet or placebo
      starting 4 months before and continuing through the pollen season. The primary
      efficacy end point was the daily Combined Score (CS; scale, 0-3), which
      integrates symptoms and rescue medication use. RESULTS: Four hundred seventy
      three participants were randomized. The mean daily CS over the pollen period was
      significantly lower in the active treatment group versus the placebo group (least
      squares mean difference: -0.13; 95% CI, -0.19 to -0.06; P = .0003; relative
      reduction: 28.2%; 95% CI, 13.0% to 43.4%). In placebo-treated participants, the
      daily CS least-squares mean was 0.32 in the subgroup with baseline timothy grass
      specific serum IgE of less than 0.1 kU/L (n = 23) and 0.46 in those with baseline
      timothy grass-specific serum IgE of 0.1 kU/L or greater (n = 204). The most
      frequent reported adverse events were oral pruritus, throat irritation, and
      nasopharyngitis. There were no reports of anaphylaxis, and no actively treated
      participant received epinephrine. CONCLUSION: In US adults with grass pollen
      induced allergic rhinoconjunctivitis, preseasonal and coseasonal treatment with
      300IR 5-grass pollen sublingual tablet demonstrated clinically meaningful
      efficacy, especially in study subjects with measurable timothy grass-specific
      serum IgE. Use of 300IR 5-grass pollen sublingual tablet was safe and well
      tolerated. A requirement for a measurable level of allergen-specific serum IgE
      should be considered in future studies in this field.

PMID- 23122535
TI  - A prospectively validated clinical risk score accurately predicts pancreatic
      fistula after pancreatoduodenectomy.
AB  - BACKGROUND: Clinically relevant postoperative pancreatic fistulas (CR-POPF) are
      serious inherent risks of pancreatic resection. Preoperative CR-POPF risk
      assessment is currently inadequate and rarely disqualifies patients who need
      resection. The best evaluation of risk occurs intraoperatively, and should guide
      fistula prevention and response measures thereafter. We sought to develop a risk
      prediction tool for CR-POPF that features intraoperative assessment and reveals
      associated clinical and economic significance. STUDY DESIGN: Based on
      International Study Group of Pancreatic Fistula classification, recognized risk
      factors for CR-POPF (small duct, soft pancreas, high-risk pathology, excessive
      blood loss) were evaluated during pancreaticoduodenectomy. An optimal risk score
      range model, selected from 3 different constructs, was first derived (n = 233)
      and then validated prospectively (n = 212). Clinical and economic outcomes were
      evaluated across 4 ranges of scores (negligible risk, 0 points; low risk, 1 to 2;
      intermediate risk, 3 to 6; high risk, 7 to 10). RESULTS: Clinically relevant
      postoperative pancreatic fistulas occurred in 13% of patients. The incidence was
      greatest with excessive blood loss. Duct size <5 mm was associated with increased
      fistula rates that rose with even smaller ducts. These factors, together with
      soft pancreatic parenchyma and certain disease pathologies, afforded a highly
      predictive 10-point Fistula Risk Score. Risk scores strongly correlated with
      fistula development (p < 0.001). Notably, patients with scores of 0 points never
      developed a CR-POPF, while fistulas occurred in all patients with scores of 9 or
      10. Other clinical and economic outcomes segregated by risk profile across the 4
      risk strata. CONCLUSIONS: A simple 10-point Fistula Risk Score derived during
      pancreaticoduodenectomy accurately predicts subsequent CR-POPF. It can be readily
      learned and broadly deployed. This prediction tool can help surgeons anticipate,
      identify, and manage this ominous complication from the outset.

PMID- 23122536
TI  - Impact of the american college of surgeons oncology group Z0011 criteria applied
      to a contemporary patient population.
AB  - BACKGROUND: The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial
      concluded that axillary lymph node dissection (ALND) may not be necessary for all
      patients with sentinel lymph node (SLN) metastasis undergoing breast-conserving
      therapy (BCT). The aim of this study was to assess applicability of Z0011 results
      to our patient population and determine what percentage may be affected by these
      results. STUDY DESIGN: Patients with clinical T1-2, N0 breast cancer, treated
      with surgery first between 1994 and 2009, who had 1 to 2 positive SLNs, were
      included in this study. Kaplan-Meier survival curves were calculated and log-rank
      used to compare overall survival (OS) and disease-free survival (DFS) for ALND vs
      SLN dissection (SLND) alone in 2 patient populations: patients undergoing BCT or
      total mastectomy (TM) and patients undergoing BCT only. RESULTS: Of 861 patients,
      188 (21.8%) underwent SLND alone. Of 488 (56.7%) patients who underwent BCT, 125
      (25.6%) had SLND alone. Of 412 patients undergoing TM, 67 (16.3%) had SLND alone.
      Patients undergoing ALND were significantly younger, had larger tumors,
      macrometastasis, and extranodal extension in both populations. Compared with the
      Z0011 cohort, our BCT patients had more T1 tumors (76.0% vs 69.3%, p = 0.01) and
      more grade II to III tumors (87.3% vs 76.2%, p < 0.0001). After adjusting for T
      stage, there were no significant differences in DFS and OS between patients
      undergoing SLND alone or ALND in both populations. CONCLUSIONS: Examination of
      our breast cancer patients with Z0011 trial criteria suggests that almost 75% of
      SLN-positive patients would be candidates to avoid ALND if they undergo BCT.

PMID- 23122538
TI  - Taxanes for breast cancer during pregnancy: a systematic review.
AB  - Landmark studies have established taxanes in the treatment of patients with
      breast cancer; however, recommendations regarding their administration during
      pregnancy are controversial. The present systematic review aims to synthesize all
      available data that stem exclusively from breast cancer case series to evaluate
      the efficacy and safety of taxanes during pregnancy. Overall, 16 studies (50
      pregnancies) were eligible for the systematic review according to prisma
      guidelines. The mean age of patients with breast cancer at pregnancy was 34.6
      years. The gestational age (GA) at chemotherapy administration varied from 12 to
      36 weeks. The mean GA at delivery was 35.9 weeks. The mean weight of babies at
      delivery was 2380 g. In 76.7% of cases, a completely healthy neonate was born; in
      the remaining cases, a neonate who was dystrophic and premature, one with mild
      hydrocephalus, one with signs of bacterial sepsis, one with hyperbilirubinemia,
      one with apnea of prematurity, respiratory distress syndrome and gastroesophageal
      reflux, one with meconium-stained fluid, and another neonate with neutropenia and
      pyloric stenosis were reported. Ninety percent of children were completely
      healthy, with a median follow-up of 16 months; in the remaining cases, one child
      with recurrent otitis media, one with immunoglobulin A deficiency and mild
      constipation, and another child with delayed speech were reported. In conclusion,
      available data suggest that taxanes may potentially play a promising role in the
      optimal therapeutic strategy of patients with breast cancer diagnosed during
      pregnancy.

PMID- 23122537
TI  - Expression of underglycosylated MUC1 antigen in cancerous and adjacent normal
      breast tissues.
AB  - INTRODUCTION: Mucin 1 antigen (MUC1) is a high-molecular-weight transmembrane
      glycoprotein with an aberrant expression profile in various malignancies,
      including breast cancer. Its increased overexpression and underglycosylation in
      breast cancer is associated with tumor invasiveness and metastatic potential. In
      this study, we took the next step toward establishing MUC1 as a potential
      diagnostic, prognostic, and therapeutic target by investigating its expression
      and posttranslational modification (glycosylation/sialylation). PATIENTS AND
      METHODS: In these studies we used a breast cancer tissue microarray (TMA) and
      fresh-frozen multistage breast cancer tissues. We analyzed in detail the
      expression of normal and underglycosylated/sialated MUC1 by immunohistochemical
      techniques, real-time quantitative reverse transcriptase-polymerase chain
      reaction (qRT-PCR), and various analytic techniques. RESULTS: We found that
      changes in cellular localization as well as in upregulation and/or
      underglycosylation of MUC1 were associated with higher tumor grade. A key finding
      in this study was that underglycosylated MUC1 (uMUC1) overexpression and
      sialation were observed in tissues adjacent to tumor but identified as normal on
      pathology reports. CONCLUSIONS: These findings suggest that uMUC1 can indeed be
      used as an early diagnostic marker and provide additional insights into breast
      cancer management.

PMID- 23122539
TI  - Should the ketogenic diet be considered for enhancing fertility?
AB  - The ketogenic diet was first developed in the 1920s as a treatment for epilepsy
      in an attempt to create a prolonged physiologic starvation state. Since that
      time, the diet has been found to have other therapeutic effects, most of which
      are neurologic. Other diets, mostly based on the principals of caloric
      restriction, have been shown to improve fertility in certain populations. We
      explore the data, both clinical and laboratory, for potential fertility enhancing
      benefits of the ketogenic diet, beyond just caloric restriction or weight loss.

PMID- 23122541
TI  - Universal newborn hearing screening in Zefat, Israel: the first two years.
AB  - OBJECTIVE: Unidentified hearing loss at birth can adversely affect speech and
      language development as well as academic achievement and social-emotional
      development. Historically, moderate-to-severe hearing loss in young children was
      not detected until well beyond the newborn period. Around 0.5 to 5 in every 1000
      neonates and infants have congenital or early childhood onset sensorineural
      hearing impairment. When identification and intervention occur at no later than 6
      months of age, the infants perform much higher on school-related measures.
      Therefore, early detection is vitally important. Toward the end of 2009, the
      Israeli ministry of health issued a directive establishing a universal newborn
      hearing screening program in all hospitals in the country from 01.01.10. The
      objectives of this study are to evaluate a newly established universal newborn
      hearing screening program, to assess performance and to compare measurements of
      performance to performance benchmarks representing a consensus of expert opinion.
      The benchmarks are the minimal requirements that should be attained by high
      quality early hearing detection programs. METHODS: As specified by the ministry
      of health, a two-stage screening protocol was implemented using otoacoustic
      emissions and automated auditory brainstem response. Screening results of all
      neonates born from the initiation of the program on 15th March 2010 until the end
      of 2011 were reviewed. RESULTS: The total number of live births during the study
      period was 5496. Of these, 5334 (97%) started screening for hearing loss but only
      5212 completed the screening process, giving a screening coverage of 94.8%. Of
      the 5212 neonates completing the screening process, 270 (5.18%) were referred for
      full diagnostic testing. CONCLUSIONS: The newly established universal newborn
      hearing screening program at the Ziv Medical Center in Zefat closely approaches,
      but does not yet meet the minimal requirements that should be attained by high
      quality early hearing detection programs. Every effort should be made to complete
      the screening tests before discharge from hospital. Screening staff should
      actively encourage parents to participate in all stages of early detection.

PMID- 23122540
TI  - Impaired inter-hemispheric integration in bipolar disorder revealed with brain
      network analyses.
AB  - BACKGROUND: This represents the first graph theory-based brain network analysis
      study in bipolar disorder, a chronic and disabling psychiatric disorder
      characterized by severe mood swings. Many imaging studies have investigated white
      matter in bipolar disorder, with results suggesting abnormal white matter
      structural integrity, particularly in the fronto-limbic and callosal systems.
      However, many inconsistencies remain in the literature, and no study to date has
      conducted brain network analyses with a graph-theoretic approach. METHODS: We
      acquired 64-direction diffusion-weighted magnetic resonance imaging on 25
      euthymic bipolar I disorder subjects and 24 gender- and age-equivalent healthy
      subjects. White matter integrity measures including fractional anisotropy and
      mean diffusivity were compared in the whole brain. Additionally, structural
      connectivity matrices based on whole-brain deterministic tractography were
      constructed, followed by the computation of both global and local brain network
      measures. We also designed novel metrics to further probe inter-hemispheric
      integration. RESULTS: Network analyses revealed that the bipolar brain networks
      exhibited significantly longer characteristic path length, lower clustering
      coefficient, and lower global efficiency relative to those of control subjects.
      Further analyses revealed impaired inter-hemispheric but relatively preserved
      intra-hemispheric integration. These findings were supported by whole-brain white
      matter analyses that revealed significantly lower integrity in the corpus
      callosum in bipolar subjects. There were also abnormalities in nodal network
      measures in structures within the limbic system, especially the left hippocampus,
      the left lateral orbitofrontal cortex, and the bilateral isthmus cingulate.
      CONCLUSIONS: These results suggest abnormalities in structural network
      organization in bipolar disorder, particularly in inter-hemispheric integration
      and within the limbic system.

PMID- 23122542
TI  - Reliability and validity of the Korean version of Pediatric Voice Handicap Index:
      in school age children.
AB  - OBJECTIVE: The aim of this study was to assess the reliability and validity of
      the Pediatric Voice Handicap Index (pVHI) for cross-cultural adaptation of the
      Korean version with school age children. METHODS: The questionnaire was
      translated into Korean and was completed by 101 Korean parents who have children
      with or without disordered voice. The Korean version-pVHI scores were obtained
      with 60 parents of normal children and 41 parents who have children with voice
      problems. Content validity was verified by five experienced speech-language
      pathologists with clinical specialization in voice disorders. Internal
      consistency was calculated through Cronbach's alpha coefficient and test-retest
      reliability of the Korean version-pVHI score was determined using Pearson product
      moment correlation coefficients. Mann-Whitney U test was used to compare GRBAS
      with the Korean version-pVHI scores between normal and dysphonia group. The
      relationship between the parent-reported the Korean version-pVHI total scores and
      perceptual ratings of voice quality from experts was investigated using Spearman
      correlation coefficients. RESULTS: The results showed that the Korean version
      pVHI provided a high internal consistency (alpha=0.92) and test-retest
      reliability of its subscales: total (T) 0.97, functional (F) 0.90, physical (P)
      0.95, emotional (E) 0.92. The Korean version-pVHI mean scores in normal group
      were 1.28 (T), 0.62 (F), 0.35 (P) and 0.32 (E), respectively whereas those of the
      Korean version-pVHI in children group with dysphonia were 23.13 (T), 8.90 (F),
      9.54 (P) and 4.93 (E). Significant differences in the Korean version-pVHI (T, F,
      P, E) and perceptual evaluation (grade, rough, breathy) between normal and
      dysphonia group were revealed (P<0.05). Moreover, relatively moderate-to-high
      correlation between the Korean version-pVHI parameters (T) and perceptual
      measures (G) was exhibited in children with dysphonia. CONCLUSIONS: The
      subjective Korean version-pVHI can be applicable and useful supplementary tool
      for evaluating parents' perception of their children's voice dysfunction,
      identifying multifactors on daily life affecting their children's voice and
      measuring treatment efficacy before and after therapeutic intervention.

PMID- 23122543
TI  - Surgical outcomes of robotic radical hysterectomy after neoadjuvant chemotherapy
      for locally advanced cervical cancer: comparison with early stage disease.
AB  - AIMS: To evaluate the feasibility and safety of robotic radical hysterectomy
      (RRH) with pelvic lymphadenectomy for locally advanced cervical cancer (LACC)
      after neoadjuvant chemotherapy (NACT). METHODS: Starting from 04/2009,
      consecutive patients with LACC were submitted to robotic surgical staging after
      NACT. Surgical outcomes were compared to those achieved by women undergoing
      robotic surgery for an early stage disease during the same temporal interval.
      RESULTS: Overall 25 (Group 1) and 21 (Group 2) patients had an early stage and a
      LACC, respectively. Among women with LACC, 18 achieved best tumor responses to
      NACT and therefore they were addressed to RRH. Outcomes resulted comparable
      between Groups in terms of operative time, blood loss, hospitalization and
      complications. No differences were found in terms of nodal yield, parametrial and
      vaginal cuff length. CONCLUSIONS: RRH is feasible and safe also in patients
      previously submitted to NACT for LACC. Larger series with longer follow-up are
      mandatory to establish survival outcomes.

PMID- 23122544
TI  - Stratification of postprostatectomy urinary function using expanded prostate
      cancer index composite.
AB  - OBJECTIVE: To classify the Expanded Prostate Cancer Index Composite (EPIC)-Short
      Form urinary domain (EPIC-UIN) scores, as part of a validated health-related
      quality of life instrument after prostate cancer treatment into clinically
      meaningful functional categories. MATERIALS AND METHODS: Using a prospectively
      maintained database, approved by the institutional review board, of patients
      undergoing prostatectomy for malignancy, the patient and tumor factors and
      validated health-related quality of life instruments, including EPIC-UIN and the
      Incontinence Severity Index (ISI) were retrospectively reviewed. The
      questionnaires were completed preoperatively, at 3, 6, 9, and 12 months
      postoperatively, and yearly thereafter. Cutpoints were chosen for the EPIC-UIN
      scores to correlate with ISI, and statistical analysis querying this correlation
      was performed. RESULTS: A total of 446 patients completing 764 questionnaires
      were reviewed. On average, the patients were 59.2 years old with a Gleason score
      of 6.75. All patients underwent robotic-assisted (n=224) or radical retropubic
      (n=222) prostatectomy. The range of ISI scores at the prescribed measurement
      points was "mild" (0-6), "moderate" (7-16), and "severe" (>=17) in 58.9%, 28.9%,
      and 11.3% of patients, respectively. An EPIC-UIN score of 0-49, 50-69, and 70-100
      was chosen to correlate with the ISI score of "severe," "moderate," and "mild,"
      with an agreement of 74.1% (weighted kappa coefficient 0.6541). Severe
      incontinence and moderate incontinence on the EPIC-UIN were associated with a
      sensitivity of 74% and 90.6% and specificity of 90.2% and 93.6%, respectively.
      CONCLUSION: Categorical EPIC-UIN groups were developed to represent the mild,
      moderate, and severe incontinence. These categories provided meaningful guides
      for assessing postoperative urinary incontinence and recovery of urinary
      function.

PMID- 23122546
TI  - Five years of Stem Cell Research--reflections on progress in the field.

PMID- 23122545
TI  - Periprostatic implantation of human bone marrow-derived mesenchymal stem cells
      potentiates recovery of erectile function by intracavernosal injection in a rat
      model of cavernous nerve injury.
AB  - OBJECTIVE: To evaluate whether periprostatic implantation (PPI) of human bone
      marrow-derived mesenchymal stem cells (hBMSCs) potentiates recovery of erectile
      function after intracavernosal injection (ICI) of hBMSCs in a rat model of
      cavernous nerve (CN) injury. METHODS: Sprague-Dawley rats that had undergone
      bilateral CN injury were treated by ICI with or without PPI of hBMSCs (10 rats
      per group). hBMSCs were harvested from healthy human donors. Fibrin scaffolds
      were used for PPI of hBMSCs. After 4 weeks, erectile responses to electric pelvic
      ganglion stimulation were studied. The expression of neuronal nitric oxide
      synthase (nNOS)-positive nerve fibers and smooth muscle/collagen ratio was
      evaluated in each penis. RESULTS: ICI of hBMSCs slightly improved erectile
      function compared with the control group (maximal intracavernosal pressure/mean
      arterial pressure, 39.1% vs 21.7%; P=.060), but a combination of PPI and ICI
      significantly improved erectile function (45.0%, P=.007). After stem cell
      therapy, the number of nNOS-positive nerve fibers increased significantly in the
      PPI+ICI group (P=.017). The smooth muscle/collagen ratio increased significantly
      after stem cell therapy in the ICI and PPI+ICI groups (both P<.001). CONCLUSION:
      ICI of hBMSCs in a rat model of CN injury results in recovery of penile erection
      by decreasing corporeal smooth muscle deterioration and collagen deposition. PPI
      of hBMSCs potentiates recovery of erectile function by ICI of hBMSCs via
      regeneration of nNOS-containing nerve fibers.

PMID- 23122547
TI  - Antiphospholipid syndrome: diagnosis.

PMID- 23122548
TI  - Differential effect of right ventricular dilatation on myocardial deformation in
      patients with atrial septal defects and patients after tetralogy of Fallot
      repair.
AB  - BACKGROUND: Right ventricular (RV) volume overload results in RV dilatation in
      patients with atrial septal defect (ASD) and after tetralogy of Fallot (ToF)
      repair with pulmonary regurgitation. AIM: Study the differential effects of
      chronic RV volume loading on regional and global RV deformation in patients with
      ASD and after TOF repair. METHODS: We studied 85 subjects: 50 patients after ToF
      repair, 15 patients with unrepaired ASD and 20 age-matched controls. The ToF
      patients and controls underwent an echocardiography at the time of a clinically
      indicated MRI. The ASD patients had a routine echocardiogram including RV volume
      calculations. Longitudinal deformation was analyzed using 2-D speckle tracking
      echocardiography. RESULTS: RV free wall global and segmental longitudinal
      deformation was significantly lower in ToF patients compared with ASD and
      controls (p<0.001). In ToF patients, there was a progressive decrease in strain
      values from base to apex (p<0.001), while in the ASD group there was a
      progressive increase (p=0.04). We found strong negative correlations between RV
      size and RV longitudinal strain measurements, strongest with RV length (R=0.72).
      When corrected for RV size, all ASD patients had normal or higher deformation
      values while half of the TOF patients had significantly lower values. CONCLUSION:
      Global and regional myocardial RV deformation is differently affected by chronic
      volume loading in ASD versus TOF patients, especially regarding the apical
      function. This suggests a different adaptation mechanism in both diseases. Our
      data also suggest that strain measurements are strongly influenced by ventricular
      size, which should be taken into consideration when interpreting strain values.

PMID- 23122549
TI  - Importance of knowing stent design threshold diameters and post-dilatation
      capacities to optimise stent selection and prevent stent overexpansion/incomplete
      apposition during PCI.

PMID- 23122550
TI  - TPT1/ TCTP-regulated pathways in phenotypic reprogramming.
AB  - Evolutionary conserved and pleiotropic, the TPT1/TCTP gene (translationally
      controlled tumor protein, also called HRF, fortilin), encodes a highly structured
      mRNA shielded by ribonucleoproteins and closely resembling viral particles. This
      mRNA activates, as do viruses, protein kinase R (PKR). The TPT1/TCTP protein is
      structurally similar to mRNA-helicases and MSS4. TPT1/TCTP has recently been
      identified as a prognostic factor in breast cancer and a critical regulator of
      the tumor suppressor p53 and of the cancer stem cell (SC) compartment. Emerging
      evidence indicates that TPT1/TCTP is key to phenotypic reprogramming, as shown in
      the process of tumor reversion and possibly in pluripotency. We provide here an
      overview of these diverse functions of TPT1/TCTP.

PMID- 23122551
TI  - Science + dance = bodystorming.
AB  - In everyday life, gravity and inertial forces often dominate our movements; in
      the cell, these forces pale in comparison to thermal forces. The violent,
      collisional world of the cell, where water moves faster than a jet airliner, can
      be difficult to imagine. To develop our intuitive understanding of cellular and
      molecular processes, we are exploring the concept of 'bodystorming', where human
      'movers' act as molecules that diffuse, undergo reactions, and generate/absorb
      forces.

PMID- 23122552
TI  - Body dissatisfaction levels and gender differences in attentional biases toward
      idealized bodies.
AB  - Attentional bias toward idealized bodies (men: muscular; women: thin) may cause
      upward comparisons and increase body dissatisfaction (BD). We investigated
      attentional biases of 39 men and 41 women with high and low BD toward muscular
      male bodies and thin female bodies. An eye-tracker measured gaze durations and
      fixation frequencies while exposing participants to images of thin, normal,
      muscular, and fat bodies of the same gender. Results revealed longer and more
      frequent attention toward muscular bodies in high BD men, and toward thin bodies
      in high BD women. High BD men and women also rated muscular and thin bodies as
      more attractive than those with low BD. Although men attended to muscular and
      women attended to thin bodies, both showed an attentional bias toward body types
      they rated as more attractive. These findings could provide indirect evidence in
      explaining the relationship between BD and the social comparison theory with
      attentional bias.

PMID- 23122553
TI  - An efficient synthesis of 2-substituted benzothiazoles in the presence of
      FeCl3/Montmorillonite K-10 under ultrasound irradiation.
AB  - 2-Substituted benzothiazoles have been synthesized via one-pot reaction from
      aromatic aldehydes and o-aminothiophenol in the presence of
      FeCl(3)/Montmorillonite K-10 in absolute methanol at 25-30 degrees C under
      ultrasound irradiation. The remarkable advantages are an inexpensive and easily
      available reagent, a simple procedure, mild conditions, short reaction times and
      moderate to good yields.

PMID- 23122554
TI  - Executive functioning in anorexia nervosa patients and their unaffected
      relatives.
AB  - Formal genetic studies suggested a substantial genetic influence for anorexia
      nervosa (AN), but currently results are inconsistent. The use of the
      neurocognitive endophenotype approach may facilitate our understanding of the AN
      pathophysiology. We investigated decision-making, set-shifting and planning in AN
      patients (n=29) and their unaffected relatives (n=29) compared to healthy
      probands (n=29) and their relatives (n=29). The Iowa Gambling Task (IGT), the
      Tower of Hanoi (ToH) and the Wisconsin Card Sorting Test (WCST) were
      administered. Concordance rates and heritability indices were also calculated in
      probands/relatives. Impaired performance on the IGT and the WCST were found in
      both AN probands and their relatives, although planning appeared to be preserved.
      The IGT heritability index suggested the presence of genetic effects that
      influence this measure. No evidence for genetic effects was found for the WCST.
      The results suggest the presence of a shared dysfunctional executive profile in
      women with AN and their unaffected relatives, characterized by deficient decision
      making and set-shifting. Concordance analysis strongly suggests that these
      impairments aggregate in AN families, supporting the hypothesis that they may
      constitute biological markers for AN. Decision-making impairment presents a
      moderate heritability, suggesting that decision-making may be a candidate
      endophenotype for AN. 

PMID- 23122556
TI  - Decision-making and impulsivity in eating disorder patients.
AB  - Impairment in decision-making can be related to some pathological behaviors in
      eating disorders. This ability was assessed in 71 eating disorder patients (27
      restricting type patients and 44 binge/purging type patients) and compared with
      38 healthy controls using the Iowa Gambling Task. This task simulates real-life
      decision-making by assessing the ability to sacrifice immediate rewards in favor
      of long term gains. Furthermore, some studies have demonstrated a relationship
      between impulsivity and decision-making, so in our study the Barratt
      Impulsiveness Scale was also used. Eating disorder patients, both the restricting
      and the binge/purging groups, performed poorly in the Iowa Gambling Task compared
      to controls, confirming a deficit in decision-making in these patients. The
      restricting group showed poorer IGT performance than the binge/purging group.
      Interestingly, impulsivity was negatively correlated with decision-making, but
      only in the binge/purging group. In conclusion, our results confirm a specific
      deficit in eating disorder patients which may be related to their pathological
      eating behavior, and suggest that this impairment might be explained by different
      mechanisms in restricting and binge/purging disorders.

PMID- 23122555
TI  - Influence of depression symptoms on history-independent reward and punishment
      processing.
AB  - Prior research indicates that depressed individuals are less responsive to
      rewards and more sensitive to punishments than non-depressed individuals. This
      study examines decision-making under reward maximizing or punishment minimizing
      conditions among adults with low (n=47) or high (n=48) depression symptoms. We
      utilized a history-independent decision-making task where learning is experience
      based and the participants' goal is to enhance immediate payoff. Results
      indicated a significant interaction between incentive condition (reward
      maximizing, punishment minimizing) and depression group. Within the low
      depression group, better performance was observed for reward maximization than
      punishment minimization. In contrast, within the high depression group, better
      performance was observed for punishment minimization than reward maximization.
      Further, the high depression group outperformed the low depression symptom group
      in the punishment minimization condition, but no depression group differences
      were observed in the reward maximization condition. Computational modeling
      indicated that the high depression group was more likely to choose options with
      the highest expected reward, particularly in the punishment condition. Thus,
      decision-making is improved for people with elevated depression symptoms when
      minimizing punishment relative to maximizing rewards.

PMID- 23122557
TI  - Psychometric properties of Peters et al. delusions inventory-21 in adolescence.
AB  - We explored the psychometric properties of the Korean version of the Peters et
      al. delusions inventory-21 (PDI-21) and evaluated the item characteristics of the
      PDI-21 compared with the Magical Ideation Scale (MIS) in Korean community
      adolescents. Survey participants comprised 310 Year 10 students who were assessed
      with the following instruments: the PDI-21, the MIS, the Schizotypal Personality
      Scale (STA) and the symptom checklist-90-R (SCL-90-R). The item characteristics
      of the PDI-21 and MIS were also explored using item response theory (IRT). The
      PDI-21 exhibited good internal consistency and demonstrated significant
      correlations with the MIS, STA and all subscale scores of the SCL-90-R,
      indicating psychological distress in adolescents with high PDI-21 scores. We also
      found through IRT analysis that the PDI-21 provides more information at the lower
      range and the MIS at the higher range of delusion proneness. Our findings suggest
      that the PDI-21 is an effective and reliable self-report measure for assessment
      of delusion proneness and that the PDI-21 and the MIS may be used complementarily
      to assess a broad range of delusion proneness among community adolescents.

PMID- 23122558
TI  - Quality of life in obsessive-compulsive disorder: the role of mediating
      variables.
AB  - This study examined the association of various clinical features of obsessive
      compulsive disorder (OCD) with quality of life (QoL) in 102 adults with a
      principal diagnosis of OCD. Participants were assessed by trained clinicians
      using the Anxiety Disorders Interview Schedule 4th edition, the Yale-Brown
      Obsessive-Compulsive Scale, and an unstructured clinical interview. Subjects
      completed the MOS-36 Item Short Form Health Survey, and Beck Depression Inventory
      II. Obsessive-compulsive symptom severity was negatively correlated with
      emotional health, social functioning and general health QoL. Depressive symptoms
      mediated the relationship between obsessive-compulsive symptom severity and
      emotional health, social functioning and general health QoL. Additionally,
      interference of obsessive-compulsive symptoms mediated the relationship between
      obsessive-compulsive symptom severity and emotional health, social functioning
      and general health QoL. Resistance against obsessive-compulsive symptoms mediated
      the relationship between obsessive-compulsive symptom severity and social
      functioning QoL. Diminished QoL is present in persons with OCD and is essential
      in understanding the complete clinical picture of OCD.

PMID- 23122559
TI  - Clinical management of solitary pulmonary micronodule: a pilot study.
AB  - BACKGROUND: Solitary pulmonary micronodules (SPMN) characteristically have a
      diameter of 0.1-0.5cm. OBJECTIVE: The aim of this prospective study is to
      evaluate the surgical approach to SPMN in order to establish the most appropriate
      treatment. METHODS: Between January 2007 and June 2011, 146 SPMN patients (94
      males and 52 females) were prospectively evaluated. Patients were divided into
      two groups based on history of malignancy (Group A, 59 patients) and generic risk
      factors for lung cancer (Group B, 87 patients). After gathering patient
      information, we proposed surgery or thin-section computed tomography (TSCT)
      follow-up to both Groups. RESULTS: Preference for surgery versus TSCT follow-up
      was 90% versus 10% in Group A and 78% versus 22% in Group B, respectively. In
      Group A, we discovered 46 metastases from previous cancer (78%), 8 primary lung
      cancers (14%) and 5 benign lesions (8%). In Group B, we found 5 metastases (6%),
      13 non-small-cell lung cancer (15%) and 69 benign lesions (79%). Statistical
      analysis revealed a high positive predictive value (PPV = 0.9) between total
      surgical patients versus TSCT follow-up patients. CONCLUSIONS: The indication for
      surgery in solitary pulmonary micronodules is aimed at establishing early
      diagnosis and curing malignant disease. Our study indicates that in patients with
      previous cancer, surgery is essential. In patients with generic risk for lung
      cancer, surgical indications should be contemplated more carefully, even though
      the pulmonary malignancy rate of 21% in Group B seems to indicate the
      advisability of surgery.

PMID- 23122560
TI  - M(2)-beta(2) interaction: a basis for combined bronchodilator treatment.

PMID- 23122561
TI  - Secondary mediastinal hydatidosis.

PMID- 23122562
TI  - [The mini nutritional assessment. Twenty years contributing to nutritional
      assessment].

PMID- 23122563
TI  - Professor Charles E. Metz leaves profound legacy in ROC methodology: an
      introduction to the two Metz Memorial Issues.

PMID- 23122564
TI  - Sampling the latest work in receiver operating characteristic analysis: what does
      it mean?

PMID- 23122565
TI  - Applications of ROC analysis in medical research: recent developments and future
      directions.
AB  - With the growing focus on comparative effectiveness research and personalized
      medicine, receiver-operating characteristic analysis can continue to play an
      important role in health care decision making. Specific applications of receiver
      operating characteristic analysis include predictive model assessment and
      validation, biomarker diagnostics, responder analysis in patient-reported
      outcomes, and comparison of alternative treatment options. The authors present a
      survey of the potential applications of the method and briefly review several
      relevant extensions. Given the level of attention paid to biomarker validation,
      personalized medicine and comparative effectiveness research, it is highly likely
      that the receiver-operating characteristic analysis will remain an important
      visual and analytic tool for medical research and evidence-based medicine in the
      foreseeable future.

PMID- 23122566
TI  - Statistical methods for predicting mortality in patients diagnosed with acute
      pulmonary embolism.
AB  - RATIONALE AND OBJECTIVES: Risk stratification in pulmonary embolism (PE) guides
      patient management. The purpose of this study was to develop and test novel
      mortality risk prediction models for subjects with acute PE diagnosed using
      computed tomographic pulmonary angiography in a large cohort with comprehensive
      clinical data. MATERIALS AND METHODS: Retrospective analyses of 1596 consecutive
      subjects diagnosed with acute PE from a single, large, urban teaching hospital
      included two modern statistical methods to predict survival in patients with
      acute PE. Landmark analysis was used for 90-day mortality. Adaptive least
      absolute shrinkage and selection operator (aLASSO), a penalization method, was
      used to select variables important for prediction and to estimate model
      coefficients. Receiver-operating characteristic analysis was used to evaluate the
      resulting prediction rules. RESULTS: Using 30-day all-cause mortality outcome,
      three of the 16 clinical risk factors (the presence of a known malignancy,
      coronary artery disease, and increased age) were associated with high risk, while
      subjects treated with anticoagulation had lower risk. For 90-day landmark
      mortality, subjects with recent operations had a lower risk for death. Both
      prediction rules developed using aLASSO performed well compared to standard
      logistic regression. CONCLUSIONS: The aLASSO regression approach combined with
      landmark analysis provides a novel tool for large patient populations and can be
      applied for clinical risk stratification among subjects diagnosed with acute PE.
      After positive results on computed tomographic pulmonary angiography, the
      presence of a known malignancy, coronary artery disease, and advanced age
      increase 30-day mortality. Additional risk stratification can be simplified with
      these methods, and future work will place imaging-based prediction of mortality
      in perspective with other clinical data.

PMID- 23122567
TI  - Evaluation of the accuracy of medical tests in a region around the optimal point.
AB  - RATIONALE AND OBJECTIVES: The accuracy of medical tests is often assessed using
      the area under the entire receiver-operating characteristic (ROC) curve. However,
      this includes values that might be of no clinical importance. Evaluation of a
      portion of the curve, or a single point, requires identifying a range of clinical
      interest, which may not be obvious. The author suggests evaluating the accuracy
      of medical tests in the vicinity of the optimal point. MATERIALS AND METHODS:
      Assuming binormality, the author estimated the optimal threshold as the value
      that maximizes the generalized Youden index. The confidence interval around the
      optimal point defined a region of clinical interest; the accuracy of the medical
      test was assessed using the partial area index (PAI) and standardized partial
      area (sPA). Bootstrapping was used to estimate variances and construct confidence
      intervals. Coverage probabilities for the PAI and sPA were assessed, as was the
      size of the test to compare measures. An example using biomechanical measures
      from radiographic images of the pelvis and lumbar spine to detect disk hernia and
      spondylolisthesis is presented. RESULTS: Coverage probabilities of confidence
      intervals for the partial area measures were good. The size of the test to
      compare partial area measures was appropriate. Values of PAI and sPA varied with
      the cost/prevalence ratio. In the example, the biomechanical measures were not
      found to have significantly different accuracy around the optimal point.
      CONCLUSIONS: The PAI and sPA associated with the optimal point were found to be
      reasonable and useful measures of accuracy.

PMID- 23122568
TI  - An analytic expression for the binormal partial area under the ROC curve.
AB  - RATIONALE AND OBJECTIVES: The partial area under the receiver operating
      characteristic (ROC) curve (pAUC) is a useful summary measure for diagnostic
      studies. Unlike most summary measures that are functions of the ROC curve,
      researchers have not been aware of an analytic expression available for computing
      the pAUC for an ROC curve based on a latent binormal model. Instead, the pAUC has
      been computed using numerical integration or a rational polynomial approximation.
      Our purpose is to provide analytic expressions for the two forms of pAUC.
      MATERIALS AND METHODS: We discuss the two fundamentally different types of pAUC.
      We present analytic expressions for both types, provide corresponding proofs, and
      illustrate their application with an example comparing the performances of spin
      echo and cine magnetic resonance imaging for detecting thoracic aortic
      dissection. RESULTS: We provide an example of using the pAUC as the outcome in a
      multireader multicase analysis. We find that using the pAUC results in a more
      significant finding. CONCLUSIONS: We have provided analytic expressions for both
      types of pAUC, making it easier to compute the pAUCs corresponding to binormal
      ROC curves.

PMID- 23122569
TI  - Statistical methods for MRMC ROC studies.
AB  - RATIONALE AND OBJECTIVES: In radiology, multireader, multicase (MRMC) receiver
      operating characteristic studies are commonly used to evaluate the accuracy of
      diagnostic imaging systems. The special feature of an MRMC receiver-operating
      characteristic study requires that the same set of patients' images be examined
      by the same set of doctors. One main difficulty of analyzing MRMC data is a
      complicated correlation structure. Four commonly used methods are available for
      dealing with this complicated correlation structure. The authors conducted an
      extensive simulation study to assess the performance of these methods in finite
      sample sizes. They summarize the relative strengths and weaknesses of these
      methods and make recommendations on the use of these methods. MATERIALS AND
      METHODS: A comprehensive simulation study was conducted to assess finite-sample
      performance of these methods with continuous data. The use of these methods for
      magnetic resonance imaging to predict extracapsular extension of prostate gland
      tumors is also illustrated. RESULTS: The results indicate that when test outcomes
      are continuous, all four methods perform well for estimating the difference in
      areas under the curves for two diagnostic tests. On the basis of these results,
      it seems that any of these approaches is appropriate for analyzing an MRMC data
      set with continuous or pseudocontinuous data. CONCLUSIONS: The Dorfman-Berbaum
      Metz method is the most practical analysis method to implement in a wide variety
      of scenarios. Also, in MRMC studies, radiologists should be encouraged to use the
      entire rating scale rather than tending toward a binary "diseased" or "not
      diseased" decision.

PMID- 23122570
TI  - Multi-reader ROC studies with split-plot designs: a comparison of statistical
      methods.
AB  - RATIONALE AND OBJECTIVES: Multireader imaging trials often use a factorial
      design, in which study patients undergo testing with all imaging modalities and
      readers interpret the results of all tests for all patients. A drawback of this
      design is the large number of interpretations required of each reader. Split-plot
      designs have been proposed as an alternative, in which one or a subset of readers
      interprets all images of a sample of patients, while other readers interpret the
      images of other samples of patients. In this paper, the authors compare three
      methods of analysis for the split-plot design. MATERIALS AND METHODS: Three
      statistical methods are presented: the Obuchowski-Rockette method modified for
      the split-plot design, a newly proposed marginal-mean analysis-of-variance
      approach, and an extension of the three-sample U-statistic method. A simulation
      study using the Roe-Metz model was performed to compare the type I error rate,
      power, and confidence interval coverage of the three test statistics. RESULTS:
      The type I error rates for all three methods are close to the nominal level but
      tend to be slightly conservative. The statistical power is nearly identical for
      the three methods. The coverage of 95% confidence intervals falls close to the
      nominal coverage for small and large sample sizes. CONCLUSIONS: The split-plot
      multireader, multicase study design can be statistically efficient compared to
      the factorial design, reducing the number of interpretations required per reader.
      Three methods of analysis, shown to have nominal type I error rates, similar
      power, and nominal confidence interval coverage, are available for this study
      design.

PMID- 23122571
TI  - Simulation of unequal-variance binormal multireader ROC decision data: an
      extension of the Roe and Metz simulation model.
AB  - RATIONALE AND OBJECTIVES: Roe and Metz (RM) proposed a model for simulating
      multireader multicase (MRMC) data collected from a factorial study design in
      which readers read the same cases in all modalities. However, a major weakness of
      the RM model is that it generates data according to an equal-variance binormal
      model for each reader. This article extends the RM model by allowing the diseased
      and nondiseased decision-variable distributions to have unequal variances for
      each reader. MATERIALS AND METHODS: I show how to modify the RM model so that it
      generates data according to an unequal-variance binormal model for each reader.
      In doing so, I preserve other important characteristics of the original
      simulation input values. The mean-to-sigma ratio, which describes the
      relationship between the means and variances of the diseased and nondiseased
      decision-variable distributions, is constrained to have a value that is
      representative of many data sets. This last point is illustrated with an example
      comparing the performances of spin echo and cine magnetic resonance imaging for
      detecting thoracic aortic dissection. RESULTS: A simulation study is performed to
      assess the performance of the MRMC methods proposed by Dorfman, Berbaum, and Metz
      and by Obuchowski and Rockette using the proposed unequal variance extension of
      the RM model. The methods show either excellent or acceptable performance when
      there are at least five readers and at least 25 normal and 25 abnormal cases.
      CONCLUSIONS: The proposed extension of the RM simulation model generates data
      that are more similar to data collected from radiological studies.

PMID- 23122572
TI  - Tree-structured subgroup analysis of receiver operating characteristic curves for
      diagnostic tests.
AB  - RATIONALE AND OBJECTIVES: Multiple diagnostic tests are often available for a
      disease. Their diagnostic accuracy may depend on the characteristics of testing
      subjects. The investigators propose a new tree-structured data-mining method that
      identifies subgroups and their corresponding diagnostic tests to achieve the
      maximum area under the receiver-operating characteristic curve. MATERIALS AND
      METHODS: The Osteoporosis and Ultrasound Study is a prospectively designed,
      population-based European multicenter observational study to evaluate state-of
      the-art diagnostic methods for assessing osteoporosis. A total 2837 women
      underwent dual x-ray absorptiometry (DXA) and quantitative ultrasound (QUS).
      Prevalent vertebral fractures were determined by a centralized radiology
      laboratory on the basis of radiographs. The data-mining algorithm includes three
      steps: defining the criteria for node splitting and selection of the best
      diagnostic test on the basis of the area under the curve, using a random forest
      to estimate the probability of DXA being the preferred diagnostic method for each
      participant, and building a single regression tree to describe subgroups for
      which either DXA or QUS is the more accurate test or for which the two tests are
      equivalent. RESULTS: For participants with weights <=54.5 kg, QUS had a higher
      area under the curve in identifying prevalent vertebral fracture. For
      participants whose weights were >58.5 kg and whose heights were <=167.5 cm, DXA
      was better, and for the remaining participants, DXA and QUS had comparable
      accuracy and could be used interchangeably. CONCLUSIONS: The proposed tree
      structured subgroup analysis successfully defines subgroups and their best
      diagnostic tests. The method can be used to develop optimal diagnostic strategies
      in personalized medicine.

PMID- 23122573
TI  - What program directors think: results of the 2011 annual survey of the
      Association of Program Directors in Radiology.
AB  - RATIONALE AND OBJECTIVES: The Association of Program Directors in Radiology
      (APDR) conducts an annual survey to monitor and evaluate issues pertaining to
      radiology residents' educational experiences, work responsibilities, and
      benefits. Data are used to identify emerging trends and patterns of change to
      plan and provide resources that support radiology residency programs and their
      directors. MATERIALS AND METHODS: The APDR Annual Survey Committee selected 59
      items for an observational, cross-sectional study using a Web-based survey.
      Topics of interest included program director satisfaction, resident recruitment,
      social media, program requirements, curriculum, the new American Board of
      Radiology exam process, call, and residents-as-teachers programs. All active APDR
      members (n = 296) were invited to participate in survey between February 20 and
      March 11, 2011. RESULTS: The response rate was 47% (140 of 296). Descriptive
      results were tallied using SurveyMonkey software, and qualitative responses were
      tabulated or summarized as comments. Findings were reported during the 59th
      annual meeting of the Association of University Radiologists. CONCLUSIONS: Data
      generated by the annual survey enable the APDR to accrue data pertaining to
      residents' real-time educational experiences. In 2011, program directors were
      satisfied with their jobs but not convinced that competency-based program
      requirements had positive effect on residency training. Programs plan to use the
      Radiological Society of North America and American Association of Physicists in
      Medicine Web-based physics training modules. Most radiology programs do not have
      residents-as-teachers programs, nor do they plan to initiate them. During
      recruitment, programs use an applicant's location as a proxy for true interest in
      the program, and interest in the program is important for granting interviews and
      final ranking. Qualified international medical graduate applicants have access to
      radiology training in the United States and Canada. Almost half of radiology
      programs have in-house reading by attending radiologists with residents on call.
      Residency programs have been slow to embrace social media.

PMID- 23122574
TI  - Teaching interpersonal and communication skills.

PMID- 23122575
TI  - The relationship between insulin resistance and osteoporosis in elderly male type
      2 diabetes mellitus and diabetic nephropathy.
AB  - OBJECTIVE: Diabetes is often associated with complications and comorbidities.
      Diabetic osteoporosis (OP) is increasingly recognized as a significant
      comorbidity of type 2 diabetes mellitus (T2-DM). In this study, we intended to
      determine whether type 2 diabetes was associated with a higher bone mineral
      density (BMD) in older males, and investigate the related risk factors of
      diabetes mellitus accompanied with OP. MATERIALS AND METHODS: To assess the
      effects of diabetes and its complications on the risk of bone fractures, the
      daily glycemia, insulin and HbAlc of T2-DM patients were detected. At the same
      time, Dual Energy X-ray Absorptiometry (DEXA) was used to measure the BMD of
      whole body, lumbar spine and proximal femoral at 2-year intervals. RESULTS: The
      BMD in elderly male patients suffered from T2-DM was associated with kidney
      function. The decrease of BMD in elderly male patients with T2-DM was related to
      HbA1c and body mass index (BMI). The BMD in group of renal function insufficiency
      or clinical albuminuria which are closely related with insulin insufficiency were
      much lower than that in the group of normal control. Additionally, a
      significantly lower (P<0.05) T-score was found in patients with nephropathy as
      compared with those without the complications. CONCLUSION: The elderly patients
      with type 2 diabetes mellitus are prone to develop OP. The insufficiency of
      insulin, the decreased insulin sensitivity and diabetic nephropathy are important
      causes for OP in the patients with type 2 diabetes.

PMID- 23122576
TI  - Acromegaly induced by ectopic secretion of GHRH: a review 30 years after GHRH
      discovery.
AB  - Ectopic acromegaly is very rare and since the discovery of growth hormone
      releasing hormone (GHRH), 30 years ago, only 74 cases have been reported in the
      literature. Except for a recent French series of 21 cases, most of them were case
      reports. The present review summarizes the current knowledge on clinical
      presentation, diagnosis and prognosis. Tumors secreting GHRH are neuroendocrine
      tumors, usually well differentiated and mainly from pancreatic or bronchial
      origin. They are usually large and easy to localize using TDM and somatostatin
      receptor scintigraphy. Clinical presentation is an acromegaly of variable
      intensity, whose features are similar to that of a somatotropic adenoma.
      Pituitary may be normal or enlarged at MRI which may be difficult to interpret
      especially in MEN1 patients where the association of a microprolactinoma to a
      pancreatic tumor secreting GHRH may be misleading. GHRH plasmatic measurement has
      an excellent specificity for the diagnosis, using a threshold of 250 to 300ng/L
      and is a good tool for follow-up of patients after treatment. These tumors have a
      good overall prognosis, even in metastatic forms which represent 50% of cases.
      Surgical approach is recommended and, when a complete tumoral resection is
      feasible, results, in most patients, in long-lasting remission. In such cases,
      GHRH concentration is normalized and its increase is an accurate indicator of
      recurrence. In uncured patients, somatostatin analogs control GH secretion but
      inhibit, only partially, GHRH secretion. MEN1 mutation should be systematically
      investigated in patients with a pancreatic tumor.

PMID- 23122577
TI  - LDL-cholesterol target values and actual values in patients with type 2 diabetes
      (T2D) uncontrolled on oral antidiabetic monotherapy: the lipid results of the
      French ESCALADE survey.
AB  - AIM: While new European guidelines have recommended much lower LDL-c target
      values than current 2005 French HAS guidelines, it appears that even those ones
      are not widely implemented. This lipid-side of the ESCALADE study was designed to
      determine the LDL-c target values of GPs, diabetologists (DIABs) and
      cardiologists (CARDIOs) and the consistency of actual values in patients with
      type 2 diabetes (T2D) uncontrolled on antidiabetic monotherapy. METHODS: ESCALADE
      was a national multicentre, observational, descriptive, transversal survey. One
      thousand and three hundred GPs and 350 specialists (DIABs and CARDIOs) agreed to
      include respectively three and four patients each. For each patient, the
      physician had to set the LDL-c target value that was compared to the calculated
      HAS target value. The actual LDL-c value was recorded and compared to those
      target values. RESULTS: A total of 412 GPs, 137 DIABs and 27 CARDIOs included
      respectively 699, 364 and 66 patients. Among them 19.6% had cardiovascular
      disease (CVD) and 56.9% were on lipid-lowering therapy (LLT). The physician's
      target value was in concordance with HAS value in 37.3% (GPs), 35.4% (DIABs) and
      57.4% (CARDIOs) of the cases. Physicians overestimated the risk in respectively
      42.7%, 54.1% and 21.3%. However, very high risk was underestimated in
      respectively 38.1%, 22.0% and 25.6% of the patients and the actual LDL-c value
      was in the target range (<100mg/dL) for only 28% of the very high-risk patients.
      CONCLUSION: Physicians tend to overestimate the CVD risk in patients with T2D and
      set lower LDL-c target values than HAS calculated values. Nevertheless, patients
      with a very high risk are largely under-treated.

PMID- 23122578
TI  - Placental steroidogenesis in pregnant women with polycystic ovary syndrome.
AB  - OBJECTIVE: To evaluate the placental activity of steroid sulfatase (STS), 3beta
      hydroxysteroid dehydrogenase type 1 (3beta-HSD-1) and P450 aromatase (P450arom)
      in polycystic ovarian syndrome (PCOS) compared to normal pregnant women. DESIGN:
      Twenty pregnant women with PCOS and 30 control pregnant women who delivered at
      term were studied. Samples of placental tissue and cord blood were obtained after
      delivery. A maternal blood sample was obtained during the 34th week of gestation.
      In placental tissue, the activities of STS, 3beta-HSD-1 and P450arom were
      evaluated. In the blood samples, progesterone, DHEAS, DHEA, androstenedione,
      testosterone, estrone, estradiol and total estriol were determined. RESULT: In
      placental tissue from women with PCOS, higher 3beta-HSD-1 and lower P450
      aromatase activities were observed compared to control women. Moreover, women
      with PCOS showed higher androstenedione and testosterone concentrations compared
      to normal pregnant women (p=0.016 and p=0.025, respectively). In cord blood,
      female newborns of women with PCOS exhibited lower androstenedione and higher
      estriol concentrations compared to daughters of control women (p=0.038; p=0.031,
      respectively). CONCLUSION: These data suggest that placental tissue from women
      with PCOS shows changes in the activities of two important enzymes for steroid
      synthesis, higher 3beta-HSD-1 and lower P450, which could increase androgen
      production during pregnancy.

PMID- 23122579
TI  - Preoperative planning of surgery for deeply infiltrating endometriosis using the
      ENZIAN classification.
AB  - OBJECTIVE: To use the ENZIAN classification for preoperative estimation of
      laparoscopic operating time in patients with deeply infiltrating endometriosis
      (DIE). STUDY DESIGN: Retrospective study of women with DIE (n=151) who underwent
      laparoscopic surgery. RESULTS: 151 of 470 patients had DIE (n=205 lesions)
      exclusively in compartments A (rectovaginal septum, vagina), B (sacrouterine
      ligament to the pelvic wall) and C (rectum, sigmoid colon). These
      laparoscopically treated lesions were used to calculate a model for estimating
      operating time for DIE, assuming complication-free procedures (overall
      significance for model's predictive power: P<0.001). The error of estimation for
      the operating time prediction is 0 +/- 35.35 min (mean +/- SD; range -83 to +117
      min). The actual operating time for all operations was 109.32 +/- 74.38 min (mean
      +/- standard deviation). CONCLUSIONS: Using a model for predicting operating time
      based on the ENZIAN classification enables resources to be planned more precisely
      in surgery management. Patients with DIE can also be given more precise
      information regarding the expected operating time.

PMID- 23122580
TI  - Association between childhood psychosocial factors and induced abortion.
AB  - OBJECTIVE: To examine the predictive associations between psychosocial risk
      factors in childhood and having an abortion in adolescence or young adulthood.
      STUDY DESIGN: This study is based on a nationwide cohort consisting of 2867 girls
      born in Finland in 1981. The baseline assessment was conducted at age eight by
      three informants, and it included information on psychiatric symptoms, school
      performance and family related risk factors. Register-based follow-up data on
      abortions were collected until the end of the year when the participants turned
      28 years. They were available for 2694 participants. Cox proportional hazards
      model and logistic regression model were used for statistical analysis. RESULTS:
      Altogether 357 women (13.3%) had had an abortion for other than medical reasons
      during the follow-up. Of the childhood factors, a high level of conduct problems,
      poor school performance, family structure other than two biological parents, and
      mother with a low level of education were independently associated with having an
      abortion. Comparison of the strength of associations between childhood risk
      factors and first abortion under the age of 20 versus first abortion at a later
      age, showed no significant differences. Neither did the comparison between one
      and more abortions. CONCLUSIONS: At age eight there are already psychosocial
      factors which predict later abortion. This finding needs to be considered when
      targeting preventive interventions and developing sexual health services.

PMID- 23122581
TI  - Inhibition of hydrogen sulfide generation contributes to lung injury after
      experimental orthotopic lung transplantation.
AB  - BACKGROUND: Lung injury induced by ischemia or reperfusion significantly accounts
      for the risk of early mortality of lung transplantation (LT). Recent studies have
      demonstrated that hydrogen sulfide (H2S) and its endogenous synthase
      cystathionine-gamma-lyase (CSE) confer protection against injury induced by
      ischemia or reperfusion in various organs. This prompted us to define the role of
      CSE/H2S pathway in transplantation-induced lung injury. METHODS: We performed
      single left LT in male Sprague-Dawley rats after 3 h of cold ischemia time. H2S
      donor NaHS (14 MUmol/kg, intraperitoneally) or CSE inhibitor propargylglycine
      (37.5 mg/kg, intraperitoneally) was administered 15 min before the start of the
      LT. CSE protein expression, H2S generation, and the severity of pulmonary graft
      injuries were estimated at 24 h after reperfusion. RESULTS: Both CSE protein
      expression and H2S generation were markedly decreased in transplanted rat lungs
      compared with those in sham-operated lungs. In the lung-transplanted rats, NaHS
      administration significantly improved pulmonary function and decreased lipid
      peroxidation and myeloperoxidase activity. In addition, NaHS inhibited the
      production of interleukin 1beta but increased interleukin 10 levels in graft lung
      tissues. In contrast, propargylglycine further exacerbated pulmonary function and
      lung injuries after experimental orthotopic LT. CONCLUSIONS: To our knowledge,
      this study for the first time has demonstrated that the suppression of CSE
      expression and H2S production is associated with transplantation-induced lung
      injury. Both exogenous and endogenous H2S seem to have protective effects against
      acute LT injury by their multiple functions including antioxidation and anti
      inflammation, suggesting that modulation of H2S levels may be considered a
      potential therapeutic approach in LT.

PMID- 23122582
TI  - Diagnosis of anastomotic leak: electrolyte detection versus barium fluoroscopy.
AB  - BACKGROUND: We recently described a new method of diagnosing anastomotic leak
      using the detection of electrical changes induced by electrolyte extravasation
      from a surgically created gastric leak site in experimental rats. We sought to
      compare the sensitivity and specificity of anastomotic leak detection for this
      method to that of upper gastrointestinal (GI) barium fluoroscopy. METHODS:
      Experimental rats with a surgically created gastric leak site and controls were
      interrogated as to the presence of leak using either the electrolyte-gated leak
      detection method or upper GI barium fluoroscopy. The sensitivity and specificity
      of leak detection for the two methods were compared. RESULTS: The sensitivity and
      specificity of electrolyte-gated leak detection were both 100% (95% confidence
      interval 69-100%). Barium upper GI fluoroscopy misidentified one leak as a
      control and one control as a leak, for a sensitivity and specificity of 80% each
      (95% confidence interval 37-97%). No statistically significant difference was
      seen between electrolyte-gated leak detection and barium upper GI fluoroscopy in
      terms of the sensitivity and specificity of anastomotic leak detection.
      CONCLUSIONS: Electrolyte-gated leak detection was similarly sensitive and
      specific for anastomotic leak detection as upper GI barium fluoroscopy, the
      current standard. The electrolyte-gated method has the advantages of an inert
      contrast agent (normal saline) and the possibility of performing leak
      interrogation at the bedside. Electrolyte-gated leak detection might represent a
      plausible alternative to upper GI barium fluoroscopy for routine postoperative
      anastomotic leak surveillance after esophagectomy or other foregut surgery.

PMID- 23122583
TI  - Treating a collagen scaffold with a low concentration of nicotine promoted
      angiogenesis and wound healing.
AB  - BACKGROUND: Nicotine, one of the major pharmacologically active agents of
      cigarette smoke, has various effects on cell proliferation, and it has recently
      been reported to have angiogenic effects. In our previous study, we showed that
      the topical administration of nicotine at a low concentration accelerated wound
      healing. This study aimed to evaluate the efficacy of nicotine and synergistic
      effects of combination treatment with nicotine and basic fibroblast growth factor
      (bFGF) in a murine excisional wound model treated with artificial dermis.
      METHODS: Full-thickness defects (8 mm in diameter) were created on the backs of
      mice, and artificial dermis was sutured to the defects. Phosphate-buffered saline
      (10 MUL), nicotine (10(-3), 10(-4), or 10(-5) M), bFGF (0.5 MUg), and both bFGF
      and 10(-4) M nicotine were topically administered to the artificial dermal tissue
      for 7 d. The mice were killed on day 14, and the wound area, neoepithelium
      length, and area of newly formed capillaries in the artificial dermis were
      evaluated. RESULTS: The wound areas treated with 10(-4) M nicotine, bFGF, or bFGF
      plus 10(-4) M nicotine were significantly smaller than those in the control
      group. In these three groups, the neoepithelium in the bFGF plus 10(-4) M
      nicotine group was significantly longer than that in the other groups. There was
      no significant difference between the neoepithelium lengths of the control and
      10(-5) M nicotine groups. The 10(-3) M nicotine group displayed the least re
      epithelization among the groups. CONCLUSIONS: In this study, 10(-4) M nicotine
      induced angiogenesis in, and accelerated the healing of, wounds treated with
      artificial dermis. bFGF and nicotine had synergistic effects, and the combined
      use of nicotine and bFGF is an effective wound healing method.

PMID- 23122584
TI  - Mechanical ventilation is the determining factor in inducing an inflammatory
      response in a hemorrhagic shock model.
AB  - BACKGROUND: Hemorrhagic shock (HS) is known to induce an inflammatory response by
      activating the immune system. This response is mainly caused by primed
      polymorphonuclear granulocytes (PMNs). Trauma patients often require mechanical
      ventilation (MV), which can cause additional pulmonary and systemic inflammation.
      The aim of this study was to evaluate the role of MV in the development of
      systemic and pulmonary inflammation in a HS model in rats. MATERIALS AND METHODS:
      In male Sprague-Dawley rats, the effect of MV and HS on the systemic and
      pulmonary inflammatory responses was measured and compared. In five groups
      (control, sham, MV, HS, and MV + HS), the inflammation was measured at time point
      300 min after the start of the experiment. RESULTS: The systemic inflammatory
      response, expressed in absolute numbers of PMNs in blood and blood growth related
      oncogene (GRO-KC) levels, was significantly higher in MV rats compared with that
      in other groups. The pulmonary inflammatory response, expressed by PMNs in
      bronchoalveolar lavage fluid (BALF), BALF interleukin 6, BALF GRO-KC, and
      myeloperoxidase activity, was significantly higher in all ventilated rats
      compared with that in the controls or HS rats. There was, however, no additional
      effect of HS in MV as the inflammatory indices were similar in both groups.
      CONCLUSIONS: Our data show that HS alone has minimal effect on the development of
      inflammation. MV (alone or in combination with HS) is the determining factor in
      inducing an inflammatory response. These results emphasize the importance of
      local (pulmonary) ventilation-induced damage in the development of systemic
      inflammation.

PMID- 23122585
TI  - A multi-SNP locus-association method reveals a substantial fraction of the
      missing heritability.
AB  - There are many known examples of multiple semi-independent associations at
      individual loci; such associations might arise either because of true allelic
      heterogeneity or because of imperfect tagging of an unobserved causal variant.
      This phenomenon is of great importance in monogenic traits but has not yet been
      systematically investigated and quantified in complex-trait genome-wide
      association studies (GWASs). Here, we describe a multi-SNP association method
      that estimates the effect of loci harboring multiple association signals by using
      GWAS summary statistics. Applying the method to a large anthropometric GWAS meta
      analysis (from the Genetic Investigation of Anthropometric Traits consortium
      study), we show that for height, body mass index (BMI), and waist-to-hip ratio
      (WHR), 3%, 2%, and 1%, respectively, of additional phenotypic variance can be
      explained on top of the previously reported 10% (height), 1.5% (BMI), and 1%
      (WHR). The method also permitted a substantial increase (by up to 50%) in the
      number of loci that replicate in a discovery-validation design. Specifically, we
      identified 74 loci at which the multi-SNP, a linear combination of SNPs, explains
      significantly more variance than does the best individual SNP. A detailed
      analysis of multi-SNPs shows that most of the additional variability explained is
      derived from SNPs that are not in linkage disequilibrium with the lead SNP,
      suggesting a major contribution of allelic heterogeneity to the missing
      heritability.

PMID- 23122586
TI  - Mutations in OTOGL, encoding the inner ear protein otogelin-like, cause moderate
      sensorineural hearing loss.
AB  - Hereditary hearing loss is characterized by a high degree of genetic
      heterogeneity. Here we present OTOGL mutations, a homozygous one base pair
      deletion (c.1430 delT) causing a frameshift (p.Val477Glufs(*)25) in a large
      consanguineous family and two compound heterozygous mutations, c.547C>T
      (p.Arg183(*)) and c.5238+5G>A, in a nonconsanguineous family with moderate
      nonsyndromic sensorineural hearing loss. OTOGL maps to the DFNB84 locus at
      12q21.31 and encodes otogelin-like, which has structural similarities to the
      epithelial-secreted mucin protein family. We demonstrate that Otogl is expressed
      in the inner ear of vertebrates with a transcription level that is high in
      embryonic, lower in neonatal, and much lower in adult stages. Otogelin-like is
      localized to the acellular membranes of the cochlea and the vestibular system and
      to a variety of inner ear cells located underneath these membranes. Knocking down
      of otogl with morpholinos in zebrafish leads to sensorineural hearing loss and
      anatomical changes in the inner ear, supporting that otogelin-like is essential
      for normal inner ear function. We propose that OTOGL mutations affect the
      production and/or function of acellular structures of the inner ear, which
      ultimately leads to sensorineural hearing loss.

PMID- 23122587
TI  - Mutations of the gene encoding otogelin are a cause of autosomal-recessive
      nonsyndromic moderate hearing impairment.
AB  - Already 40 genes have been identified for autosomal-recessive nonsyndromic
      hearing impairment (arNSHI); however, many more genes are still to be identified.
      In a Dutch family segregating arNSHI, homozygosity mapping revealed a 2.4 Mb
      homozygous region on chromosome 11 in p15.1-15.2, which partially overlapped with
      the previously described DFNB18 locus. However, no putative pathogenic variants
      were found in USH1C, the gene mutated in DFNB18 hearing impairment. The
      homozygous region contained 12 additional annotated genes including OTOG, the
      gene encoding otogelin, a component of the tectorial membrane. It is thought that
      otogelin contributes to the stability and strength of this membrane through
      interaction or stabilization of its constituent fibers. The murine orthologous
      gene was already known to cause hearing loss when defective. Analysis of OTOG in
      the Dutch family revealed a homozygous 1 bp deletion, c.5508delC, which leads to
      a shift in the reading frame and a premature stop codon, p.Ala1838ProfsX31.
      Further screening of 60 unrelated probands from Spanish arNSHI families detected
      compound heterozygous OTOG mutations in one family, c.6347C>T (p.Pro2116Leu) and
      c. 6559C>T (p.Arg2187X). The missense mutation p.Pro2116Leu affects a highly
      conserved residue in the fourth von Willebrand factor type D domain of otogelin.
      The subjects with OTOG mutations have a moderate hearing impairment, which can be
      associated with vestibular dysfunction. The flat to shallow "U" or slightly
      downsloping shaped audiograms closely resembled audiograms of individuals with
      recessive mutations in the gene encoding alpha-tectorin, another component of the
      tectorial membrane. This distinctive phenotype may represent a clue to orientate
      the molecular diagnosis.

PMID- 23122588
TI  - Mutations in COX7B cause microphthalmia with linear skin lesions, an
      unconventional mitochondrial disease.
AB  - Microphthalmia with linear skin lesions (MLS) is an X-linked dominant male-lethal
      disorder associated with mutations in holocytochrome c-type synthase (HCCS),
      which encodes a crucial player of the mitochondrial respiratory chain (MRC).
      Unlike other mitochondrial diseases, MLS is characterized by a well-recognizable
      neurodevelopmental phenotype. Interestingly, not all clinically diagnosed MLS
      cases have mutations in HCCS, thus suggesting genetic heterogeneity for this
      disorder. Among the possible candidates, we analyzed the X-linked COX7B and found
      deleterious de novo mutations in two simplex cases and a nonsense mutation, which
      segregates with the disease, in a familial case. COX7B encodes a poorly
      characterized structural subunit of cytochrome c oxidase (COX), the MRC complex
      IV. We demonstrated that COX7B is indispensable for COX assembly, COX activity,
      and mitochondrial respiration. Downregulation of the COX7B ortholog (cox7B) in
      medaka (Oryzias latipes) resulted in microcephaly and microphthalmia that
      recapitulated the MLS phenotype and demonstrated an essential function of complex
      IV activity in vertebrate CNS development. Our results indicate an evolutionary
      conserved role of the MRC complexes III and IV for the proper development of the
      CNS in vertebrates and uncover a group of mitochondrial diseases hallmarked by a
      developmental phenotype.

PMID- 23122589
TI  - Loss-of-function mutations in LRRC6, a gene essential for proper axonemal
      assembly of inner and outer dynein arms, cause primary ciliary dyskinesia.
AB  - Primary ciliary dyskinesia (PCD) is a group of autosomal-recessive disorders
      resulting from cilia and sperm-flagella defects, which lead to respiratory
      infections and male infertility. Most implicated genes encode structural proteins
      that participate in the composition of axonemal components, such as dynein arms
      (DAs), that are essential for ciliary and flagellar movements; they explain the
      pathology in fewer than half of the affected individuals. We undertook this study
      to further understand the pathogenesis of PCD due to the absence of both DAs. We
      identified, via homozygosity mapping, an early frameshift in LRRC6, a gene that
      encodes a leucine-rich-repeat (LRR)-containing protein. Subsequent analyses of
      this gene mainly expressed in testis and respiratory cells identified biallelic
      mutations in several independent individuals. The situs inversus observed in two
      of them supports a key role for LRRC6 in embryonic nodal cilia. Study of native
      LRRC6 in airway epithelial cells revealed that it localizes to the cytoplasm and
      within cilia, whereas it is absent from cells with loss-of-function mutations, in
      which DA protein markers are also missing. These results are consistent with the
      transmission-electron-microscopy data showing the absence of both DAs in cilia or
      flagella from individuals with LRRC6 mutations. In spite of structural and
      functional similarities between LRRC6 and DNAAF1, another LRR-containing protein
      involved in the same PCD phenotype, the two proteins are not redundant. The
      evolutionarily conserved LRRC6, therefore, emerges as an additional player in DA
      assembly, a process that is essential for proper axoneme building and that
      appears to be much more complex than was previously thought.

PMID- 23122590
TI  - Linkage-disequilibrium-based binning misleads the interpretation of genome-wide
      association studies.

PMID- 23122592
TI  - Scan statistics in human gene mapping.

PMID- 23122594
TI  - Enhanced anti-angiogenesis and anti-tumor activity of endostatin by chemical
      modification with polyethylene glycol and low molecular weight heparin.
AB  - Endostatin (ES), a potent endogenous angiogenesis inhibitor found in 1997 by
      O'Reilly, can effectively inhibit angiogenesis, inhibit the growth and metastasis
      of tumors. ES can also decrease drug resistance in long term and repeated
      treatment when it is used in combination with other chemotherapeutic agents. But
      there are still lots of obstacles on its clinical application, such as the need
      of a high dose to maintain its efficacy short half-life, poor stability,
      expensive, and some other shortcomings just like other protein drugs. Chemical
      modification on ES by polyethylene glycol (PEG) and low molecular weight heparin
      (LMWH) were successfully carried out in order to obtain a better ES derivative.
      Several classic experimental models were employed to study the bioactivity of ES
      and modified ES, including chicken chorioallantoic membrane (CAM) assay, corneal
      neovascularization (CNV) assay and Sarcoma 180 tumor bearing mice assay. The
      results showed that PEG-ES and LMWH-ES had better anti-angiogenesis and anti
      tumor activity than ES, which indicates that LMWH was also a good protein
      modifier.

PMID- 23122595
TI  - The reliability, accuracy and minimal detectable difference of a multi-segment
      kinematic model of the foot-shoe complex.
AB  - Kinematic models are commonly used to quantify foot and ankle kinematics, yet no
      marker sets or models have been proven reliable or accurate when wearing shoes.
      Further, the minimal detectable difference of a developed model is often not
      reported. We present a kinematic model that is reliable, accurate and sensitive
      to describe the kinematics of the foot-shoe complex and lower leg during walking
      gait. In order to achieve this, a new marker set was established, consisting of
      25 markers applied on the shoe and skin surface, which informed a four segment
      kinematic model of the foot-shoe complex and lower leg. Three independent
      experiments were conducted to determine the reliability, accuracy and minimal
      detectable difference of the marker set and model. Inter-rater reliability of
      marker placement on the shoe was proven to be good to excellent (ICC=0.75-0.98)
      indicating that markers could be applied reliably between raters. Intra-rater
      reliability was better for the experienced rater (ICC=0.68-0.99) than the
      inexperienced rater (ICC=0.38-0.97). The accuracy of marker placement along each
      axis was <6.7 mm for all markers studied. Minimal detectable difference (MDD90)
      thresholds were defined for each joint; tibiocalcaneal joint--MDD90=2.17-9.36
      degrees , tarsometatarsal joint--MDD90=1.03-9.29 degrees  and the
      metatarsophalangeal joint--MDD90=1.75-9.12 degrees . These thresholds proposed
      are specific for the description of shod motion, and can be used in future
      research designed at comparing between different footwear.

PMID- 23122596
TI  - The influence of motion control shoes on the running gait of mature and young
      females.
AB  - BACKGROUND: This study compared the running gait of mature and young females, and
      investigated the effect of a motion control shoe. First, it was hypothesised that
      in a neutral shoe, mature females would display significantly greater rearfoot
      eversion, knee internal rotation and external adductor moments when compared to a
      younger group. Secondly, the motion control shoe would reduce rearfoot eversion
      and knee internal rotation in both groups. Thirdly it was hypothesised that the
      motion control shoe would increase knee external adductor moment, through an
      increase in knee varus and moment arm. METHODS: 15 mature (40-60 years) and 15
      young (18-25 years) females performed 10 running trials at 3.5ms(-1)+/-5% over a
      force platform. Two shoes were tested, the Adidas Supernova Glide (neutral), and
      the Adidas Supernova Sequence (motion control). Ankle and knee joint dynamics
      were analysed for the right leg, and the mean of ten trials was calculated. Joint
      moments were calculated using inverse dynamics. FINDINGS: In the neutral
      condition, mature females presented greater peak rearfoot eversion, knee internal
      rotation, and external adductor moments than young females (p<0.05). A motion
      control shoe significantly reduced peak rearfoot eversion and knee internal
      rotation among both groups (p<0.05). No between shoe differences in knee external
      adductor moment were observed. INTERPRETATION: A motion control shoe is
      recommended to reduce risk of injury associated with rearfoot eversion and knee
      internal rotation in mature females. However since the knee external adductor
      moment is a variable commonly associated with medial knee loading it is suggested
      that alternative design features are required to influence this moment.

PMID- 23122597
TI  - Young and old adults prioritize dynamic stability control following gait
      perturbations when performing a concurrent cognitive task.
AB  - There are conflicting results regarding the effect of aging on postural
      prioritization. The present study investigated balance recovery performance of
      young and old adults following unexpected gait perturbations in a dual task
      condition. Thirty-two young and 30 elderly male subjects were assigned to either
      control or dual task group. After baseline assessment, an unexpected gait
      perturbation was induced by a sudden change of surface rigidity. The dual task
      groups performed a mental arithmetic task. Dynamic stability was quantified based
      on the 'extrapolated center of mass' concept. The margin of stability decreased
      significantly at touchdown of the recovery leg following the unexpected
      perturbation (P) compared with baseline (base), yet irrespective of cognitive
      load (base: -4.63cm; P: -13.32cm; p<0.05). The number of errors in the cognitive
      task increased significantly (base: 0.13; P: 0.48; p<0.05) in both age groups.
      Since the stability performance was unaffected by additional cognitive load,
      whereas the cognitive task performance declined following the perturbation in
      both groups, it is concluded that postural prioritization occurs independent of
      age in response to unexpected gait perturbations.

PMID- 23122598
TI  - A history of alternative reinforcement reduces stimulus generalization of ethanol
      seeking in a rat recovery model.
AB  - BACKGROUND: Longer periods of recovery reduce the likelihood of relapse, which
      may be due to a reduced ability of various stimuli to occasion alcohol or drug
      seeking. However, this hypothesis remains largely uninvestigated. METHODS: Here
      we assessed the ability of intermediate stimuli to occasion responding for
      ethanol in rats trained to discriminate an 8 kHz tone signaling a food fixed
      ratio (FR) of 5 and an ethanol FR5, from a 16 kHz tone signaling a food FR150 and
      ethanol FR5. In the presence of the 8 kHz tone responding for food predominates,
      and in the presence of the 16 kHz tone, responding for ethanol predominates.
      RESULTS: In the context of alternation between these conditions, varying the tone
      from 8 to 16 kHz produces a graded increase in ethanol (versus food) responding,
      consistent with a stimulus generalization function. A recent history of
      responding under food-predominant choice conditions, either during the test
      session or in the four sessions that precede it shifts the generalization
      function downwards. Extending this history to nine sessions shifts the curve
      further downwards. The stimulus generalization function was similar in a separate
      group, trained with different relative ratios for food and ethanol, but with
      similar behavioral allocation under each discriminative stimulus. Finally,
      withholding access to food and ethanol for 4 or 16 sessions did not affect the
      stimulus generalization gradient. CONCLUSION: These results suggest that longer
      histories of reinforced alternative behavior might reduce the likelihood of
      relapse by decreasing the control exerted over alcohol- or drug-seeking by
      stimuli similar to those that previously occasioned alcohol- or drug-seeking.

PMID- 23122599
TI  - Polysubstance and alcohol dependence: unique abnormalities of magnetic resonance
      derived brain metabolite levels.
AB  - BACKGROUND: Although comorbid substance misuse is common in alcohol dependence,
      and polysubstance abusers (PSU) represent the largest group of individuals
      seeking treatment for drug abuse today, we know little about potential brain
      abnormalities in this population. Brain magnetic resonance spectroscopy studies
      of mono-substance use disorders (e.g., alcohol or cocaine) reveal abnormal levels
      of cortical metabolites (reflecting neuronal integrity, cell membrane
      turnover/synthesis, cellular bioenergetics, gliosis) and altered concentrations
      of glutamate and gamma-aminobutyric acid (GABA). The concurrent misuse of several
      substances may have unique and different effects on brain biology and function
      compared to any mono-substance misuse. METHODS: High field brain magnetic
      resonance spectroscopy at 4 T and neurocognitive testing were performed at one
      month of abstinence in 40 alcohol dependent individuals (ALC), 28 alcohol
      dependent PSU and 16 drug-free controls. Absolute metabolite concentrations were
      calculated in anterior cingulate (ACC), parieto-occipital (POC) and dorso-lateral
      prefrontal cortices (DLPFC). RESULTS: Compared to ALC, PSU demonstrated
      significant metabolic abnormalities in the DLPFC and strong trends to lower GABA
      in the ACC. Metabolite levels in ALC and light drinking controls were
      statistically equivalent. Within PSU, lower DLPFC GABA levels are related to
      greater cocaine consumption. Several cortical metabolite concentrations were
      associated with cognitive performance. CONCLUSIONS: While metabolite
      concentrations in ALC at one month of abstinence were largely normal, PSU showed
      persistent and functionally significant metabolic abnormalities, primarily in the
      DLPFC. Our results point to specific metabolic deficits as biomarkers in
      polysubstance misuse and as targets for pharmacological and behavioral PSU
      specific treatment.

PMID- 23122601
TI  - Angled abutments result in increased or decreased stress on surrounding bone of
      single-unit dental implants: a finite element analysis.
AB  - The influence of angled abutments on stress is a matter of debate. It is widely
      accepted that increased stress on implants and bone has been associated with the
      use of angled abutments. However, comparisons of clinical success rates of
      implants restored with angled and straight abutments indicate no significant
      differences. The aim of the present study was to determine whether angled
      abutments could result in decreased stress on surrounding bone of single-unit
      dental implants. By means of finite element analysis (FEA), four simplified
      models were designed to simulate clinical scenarios in which that implants were
      placed in an ideal axial position or at an angled position. Each implant was
      paired with a straight or angled abutment. A simulated occlusal load of 100 N was
      applied along the vertical axis of the jawbone. The von Mises stress and strain
      were recorded for each model. The numerical results showed that angled abutments
      resulted in decreased stresses when implants were not placed in ideal axial
      position. The present study identified by means of FEA that angled abutments
      could result in decreased stress on the supporting bone of implant system and may
      provide some clues to resolve the debate regarding the influence of angled
      abutments.

PMID- 23122600
TI  - Emerging adults' treatment outcomes in relation to 12-step mutual-help attendance
      and active involvement.
AB  - BACKGROUND: Participation in Alcoholics Anonymous (AA) and Narcotics Anonymous
      (NA) during and following treatment has been found to confer recovery-related
      benefit among adults and adolescents, but little is known about emerging adults
      (18-24 years). This transitional life-stage is distinctive for greater distress,
      higher density of psychopathology, and poorer treatment and continuing care
      compliance. Greater knowledge would inform the utility of treatment referrals to
      12-step organizations for this age-group. METHODS: Emerging adults (N=303; 18-24
      years; 26% female; 95% White; 51% comorbid [SCID-derived] axis I disorders)
      enrolled in a naturalistic study of residential treatment effectiveness assessed
      at intake, 3, 6, and 12 months on 12-step attendance and involvement and
      treatment outcomes (percent days abstinent [PDA]; percent days heavy drinking
      [PDHD]). Lagged hierarchical linear models (HLMs) tested whether attendance and
      involvement conferred recovery benefits, controlling for a variety of confounds.
      RESULTS: The percentage attending 12-step meetings prior to treatment (36%) rose
      sharply at 3 months (89%), was maintained at 6 months (82%), but declined at 12
      months (76%). Average attendance peaked at about 3 times per week at 3 months
      dropping to just over once per week at 12 months. Initially high, but similarly
      diminishing, levels of active 12-step involvement were also observed. Lagged HLMs
      found beneficial effects for attendance, but stronger effects, which increased
      over time, for active involvement. Several active 12-step involvement indices
      were associated individually with outcome benefits. CONCLUSIONS: Ubiquitous 12
      step organizations may provide a supportive recovery context for this high-risk
      population at a developmental stage where non-using/sober peers are at a premium.

PMID- 23122602
TI  - Hierarchical model-based tracking of cervical vertebrae from dynamic biplane
      radiographs.
AB  - We present a novel approach for automatically, accurately and reliably
      determining the 3D motion of the cervical spine from a series of stereo or
      biplane radiographic images. These images could be acquired through a variety of
      different imaging hardware configurations. We follow a hierarchical, anatomically
      aware, multi-bone approach that takes into account the complex structure of
      cervical vertebrae and inter-vertebrae overlapping, as well as the temporal
      coherence in the imaging series. These significant innovations improve the speed,
      accuracy, reliability and flexibility of the tracking process. Evaluation on
      cervical data shows that the approach is as accurate (average precision 0.3 mm
      and 1 degrees ) as the expert human-operator driven method that was previously
      state of the art. However, unlike the previously used method, the hierarchical
      approach is automatic and robust; even in the presence of implanted hardware.
      Therefore, the method has solid potential for clinical use to evaluate the
      effectiveness of surgical interventions.

PMID- 23122603
TI  - Early pregnancy diagnosis in dairy cows using circulating nucleic acids.
AB  - Early and accurate pregnancy diagnosis in dairy cattle is a prerequisite for
      successful herd management. However, most of the currently available methods
      allow an early diagnosis only approximately 30 days after insemination. Recently,
      circulating nucleic acids (CNAs) have been used successfully as biomarkers in
      prenatal diagnosis at different gestational stages in human and animals. Here we
      show that CNAs can also be used as markers for the detection of early pregnancy
      in cattle. Serum samples were collected from multiparous pregnant (N = 24) and
      nonpregnant (N = 16) dairy cows at different days after insemination (Days 0, 20,
      and 40). Isolated serum DNA was preprocessed using a modified serial analysis of
      gene expression technique, which generated concatemerized short sequence tags for
      downstream next generation sequencing. Bioinformatic analysis identified sequence
      tags specific for pregnant dairy cows at Day 20 after insemination. The
      identified CNA-tags originated from repetitive regions of the bovine genome. Tag
      sequences that showed increased hit counts per animal were used to design
      quantitative real-time polymerase chain reaction assays. These quantitative
      polymerase chain reaction assays were applied to CNA samples from matched
      pregnant (N = 12) and nonpregnant cows (N = 16) at different times after
      insemination (Day 0, 20, and 40). At Day 20 after insemination the quantities of
      the interspersed repeats Art2A and BovB were increased in the pregnant cows
      compared with the nonpregnant control cows (P < 0.05). The best performing CNA
      biomarker BovB yielded an area under the receiver operating characteristic curve
      of 0.76. At a defined cutoff value, the pregnant and the control groups can be
      distinguished with a sensitivity of 83% and specificity of 75%. These results
      suggest that CNAs can be used as biomarkers for the detection of early pregnancy
      in cattle.

PMID- 23122604
TI  - Sex-dependent insulin like growth factor-1 expression in preattachment equine
      embryos.
AB  - An adjustment of sex ratio of offspring to the conditions present at conception
      is seen in many mammals including horses. This depends on preferential survival
      of male embryos under conditions of high energy intake. In several species,
      growth factors including insulin like growth factor (IGF)-1 have been shown to
      promote embryonic development by decreasing apoptosis and increasing cell
      proliferation. We hypothesized that sex-related differences in IGF-1 expression
      in equine embryos during the phase of maternal recognition of pregnancy might
      exist and thus contribute to preferential survival of embryos from either of both
      sexes under specific environmental conditions. Insulin like growth factor-1 mRNA
      expression of in vivo-produced equine embryos on different days of pregnancy (Day
      8, N = 6; Day 10, N = 8; Day 12, N = 14) was analyzed. Insulin like growth factor
      1 mRNA expression was evaluated by reverse transcription quantitative polymerase
      chain reaction. The sex of the embryo was determined by detection of X
      inactivation specific transcript (Xist) RNA and equine sex determining region of
      the Y chromosome DNA. Embryos positive for Xist expression were classified as
      female, and Xist negative and equine sex determining region of the Y chromosome
      positive embryos were classified as male. From 28 embryos tested, 15 (54%) showed
      positive Xist expression and were thus classified as female. Insulin like growth
      factor-1 mRNA expression was influenced by sex (P = 0.01) but not by day of
      pregnancy (relative expression of IGF-1 in relation to beta-actin, Day 8: male
      5.1 +/- 2.1, female 11.4; Day 10: male 5.2 +/- 1.6, female 17.4 +/- 6.7; Day 12:
      male 2.6 +/- 0.3, female 11.6 +/- 2.4). Results demonstrate an increased
      expression of IGF-1 in female equine embryos. Sex-related influences on
      expression of the IGF system are probably related to a gradual X chromosome
      inactivation.

PMID- 23122605
TI  - Adenomyosis in the bovine uterus: correlation between frequency, age, and 17beta
      estradiol-progesterone equilibrium.
AB  - Adenomyosis of the uterus is characterized by the presence of islands of
      endometrial glands and stroma within the myometrium. Etiopathology of adenomyosis
      has not been clearly defined but it potentially interferes reproductive processes
      in cattle. The aim of this initial study was to evaluate the impact of age on the
      frequency of adenomyosis in cows. Endometrial tissues collected from cows
      slaughtered between Day 8 and 12 of the estrous cycle (N = 72) were divided into
      two age groups: (1) 2 to 4 years old (N = 36) and (2) 5 years old and older (N =
      36). The tissues were stained with hematoxylin and eosin. The adenomyosis
      histopathomorphologic stage was classified on a four-point scale according to the
      penetration of endometrial structures inside the perimetrium. The protein
      expression of the 17-beta estradiol (E2) and progesterone (P4) receptors were
      evaluated in the endometrial tissue samples by immunohistochemistry and Western
      blot analysis, and E2 and P4 concentrations were measured in the peripheral blood
      and uterine tissue. Adenomyosis was observed in 38 of the cows examined including
      13 of the 2- to 4-year-old cows and 25 of the cows 5 years old or older. The
      frequency and intensity of adenomyosis increased with age. Higher E2 receptor
      protein expression was observed in adenomyotic cows and increased with disease
      development and increase of number of glands inside the uterus in the direction
      of perimetrium, and P4 receptor protein expression were unchanged in healthy and
      adenomyotic cows. An increase in the expression of E2 receptors and high,
      supraphysiological levels of E2 was detected in cows with III and IV degree of
      adenomyosis (P < 0.05). Overexpression of E2 receptor and alternations in E2
      secretion might make the bovine uterus susceptible to a growth advantage of
      adenomyotic tissue over the surrounding myometrium. The pathogenesis and
      immunoendocrine mechanisms controlling adenomyosis in cattle warrant further
      study.

PMID- 23122606
TI  - Green tea polyphenols added to IVM and IVC media affect transcript abundance,
      apoptosis, and pregnancy rates in bovine embryos.
AB  - Three experiments were conducted to examine the effects of green tea polyphenols
      (GTP) during IVM and IVC on apoptosis and relative transcript abundance (RA) of
      three genes controlling antioxidant enzymes, as well as subsequent pregnancy
      rates. In experiment 1, oocytes were matured in the presence of 0, 10, 15, or 25
      MUM GTP for 24 hours. The GTP dose applied to IVM medium was followed by the same
      dose supplemented to IVC medium, so oocytes and embryos of a given group were
      cultured in similar conditions. This resulted in a total of four groups (three
      experimental groups and the control). After IVF, presumptive zygotes were
      cultured in medium containing 0 to 25 MUM GTP for 8 days. The addition of 15 MUM
      GTP during IVM and IVC increased RA of SOD1, CAT, and GPX genes in blastocysts
      compared with the control (P < 0.05). Increase in GTP doses from 15 to 25 MUM did
      not further increase the transcript level. In experiment 2, effects of GTP doses
      on apoptosis were investigated in bovine blastocysts. Two of the applied GTP
      doses (10 and 15 MUM) decreased the apoptotic index (AI) in blastocysts (7.4% and
      6.2% respectively) compared with the control (9.3%; P < 0.05). However, the
      highest GTP dose used (25 MUM) caused an increase in AI compared with a dose of
      15 MUM (P < 0.05). Considering the results of experiment 1 and 2, the effects of
      15 MUM GTP treatment during IVM and IVC on pregnancy rate was evaluated after
      embryo transfer in experiment 3. Cows receiving embryos treated with 15 MUM GTP
      had higher pregnancy rates on Day 30 (34.8% vs. 28.6%) and Day 60 (34.8% vs.
      23.9%) than those receiving control embryos (P < 0.05). In conclusion, addition
      of 15 MUM GTP during IVM and IVC improved pregnancy rates; this improvement
      seemed to be associated with the increase of RA of antioxidant enzyme genes and
      the decrease in AI in bovine blastocysts.

PMID- 23122608
TI  - [Estimation of the "vascular age" based on body mass index in a population in
      primary prevention. Association with subclinical carotid atherosclerosis].
AB  - BACKGROUND AND OBJECTIVES: To know the relationship between "vascular age" (VA)
      and the diagnosis of subclinical atherosclerosis could improve cardiovascular
      risk stratification. OBJECTIVES: 1) to know the VA in a primary prevention
      population, and 2) to determine the relationship between VA and the presence of
      carotid atherosclerotic plaque (CAP). PATIENTS AND METHODS: We calculated VA
      based on body mass index (BMI). We obtained the difference between VA and
      chronological age (Delta). The screening of CAP was done by ultrasound. We
      analyzed the association between quintiles of VA and Delta with the presence of
      CAP. ROC analysis was performed. RESULTS: In total, 411 patients were included
      (age 47 [10] years, 54% men). The VA and Delta were 55 (15) and 7 (9) years
      respectively. In 75% of the patients VA was higher than the chronological age
      (50%>= 6 years). Subjects with CAP had significantly higher VA (66 [11] versus 50
      [14] years, P<.0001) and Delta (13 [9] versus 5 [7] years, P<.0001) than subjects
      without CAP. We observed a positive association of quintiles of VA and Delta with
      the prevalence of CAP. The area under de curve and the optimal cutoff point of VA
      for the detection of CAP were 0.813 and 60 years, respectively, and for Delta,
      0,771 and 11 years, respectively. CONCLUSIONS: The VA based on BMI could be a
      simple tool to estimate the presence of CAP and improve cardiovascular risk
      stratification in patients in primary prevention.

PMID- 23122609
TI  - [Respondent-driven sampling for the study of difficult access populations].

PMID- 23122607
TI  - [Prognostic value of troponin in patients with acute heart failure attended in
      Spanish Emergency Departments: TROPICA study (TROPonin in acute heart failure)].
AB  - BACKGROUND AND OBJECTIVE: To determine whether positive or negative troponin
      values determined in the Emergency Department (ED) in patients with acute heart
      failure (AHF) can predict short-term evolution (30-day intrahospitalary mortality
      and reconsultation at 30 days). PATIENTS AND METHODS: A retrospective,
      analytical, multicenter study with a follow-up of cohorts including patients
      diagnosed with AHF using the Framingham clinical criteria. Patients with acute
      coronary syndrome concomitant with AHF were excluded. Data were collected at
      baseline and during the acute episode in each case. Troponin was considered as a
      dependent variable and variables of outcome results included intrahospitalary
      mortality and mortality and reconsultation to the ED within the following 30
      days. Hazard ratios (HR) adjusted for differences in the basal state and during
      the acute episode, were calculated with their 95% confidence intervals (CI 95%)
      for troponin positive patients. RESULTS: We included 806 patients from 17 Spanish
      EDs, 250 of whom (31%) were troponin-positive. The global intrahospitalary
      mortality was 9.2%, being 10.4% at 30 days and 21.3% reconsulted to the ED within
      30 days. The troponin positive patients had a greater intrahospitalary (HR: 3.85;
      CI 95%: 2.33-6.34) 30-day mortality (HR: 3.07; CI 95%: 1.98-4.78) but not a
      greater reconsultation to the ED within 30 days (HR: 0.88; CI 95%: 0.62-1.26).
      All these findings were maintained after adjustment for the presence of chronic
      renal insufficiency, functional dependence, reduced glomerular filtration,
      treatment with nitroglycerin, with angiotensin enzyme inhibitors or angiotensin
      ii receptor antagonists in the ED and on hospital admission. CONCLUSION: Troponin
      positivity in the ED in patients with AHF is independently associated with a
      greater intrahospitalary and 30-day mortality but not with a greater rate of
      reconsultation to the ED during the following 30 days. The availability of
      troponin analysis in all EDs makes its determination recommended in all patients
      with AHF to allow evaluation of early short-term prognosis.

PMID- 23122610
TI  - [Relationship between short-term exposure to atmospheric sulfur dioxide and
      obstructive lesions in acute coronary syndrome].
AB  - BACKGROUND AND OBJECTIVES: Urban air pollutants are composed of a heterogeneous
      mixture of substances in gas and aerosol states. The aim of this study was to
      compare the effects caused by exposure to contaminants in the gas phase and
      atmospheric particles in ambient air in patients hospitalized for acute coronary
      syndrome (ACS) regarding the presence or absence of significant obstructive
      lesions (SOL) in epicardial coronary arteries. PATIENTS AND METHODS:
      Prospectively analyzed a total of 2,110 patients with a diagnosis of ACS. We
      determined the mean concentrations of contaminants in the gas phase and
      atmospheric particles from the day before until 7 days prior to admission (1 to 7
      days lag time). We divided the study population into those with presence or
      absence of SOL. RESULTS: Of the 2,110 patients with ACS, 1,892 presented SOL and
      218 without SOL. When comparing the concentrations of contaminants in the gas
      phase, we observed that the sulfur dioxide in patients with SOL had a trend
      toward higher values (10.93 +/- 8.33 versus 9.31 +/- 6.77 MUg/m(3); P = .004).
      Multivariate analysis shows that for every 10 MUg/m(3) increase of sulfur
      dioxide, there is an increase in the risk of hospitalization for ACS with SOL a
      41% (odds ratio 1.41; 95% confidence interval 1.039-1.931; P = .028).
      CONCLUSIONS: In our study population, exposure to high concentrations of sulfur
      dioxide is a precipitating factor for admission of patients with ACS and SOL.

PMID- 23122611
TI  - [Adverse events associated with vascular catheters in Emergency].

PMID- 23122612
TI  - [Hemorrhoidal disease].

PMID- 23122613
TI  - [(18)F-fluorodeoxyglucose positron emission tomography/computed tomography and
      unknown origin primary tumor. Current usefulness and future perspectives].

PMID- 23122614
TI  - [Feasibility of donors-after-cardiac-death and capnography].

PMID- 23122615
TI  - [Classic Kaposi sarcoma associated with IgG deficiency].

PMID- 23122617
TI  - Biosensors: then and now.

PMID- 23122616
TI  - Attenuated Escherichia coli strains expressing the colonization factor antigen I
      (CFA/I) and a detoxified heat-labile enterotoxin (LThK63) enhance clearance of
      ETEC from the lungs of mice and protect mice from intestinal ETEC colonization
      and LT-induced fluid accumulation.
AB  - Although enterotoxigenic Escherichia coli (ETEC) infections are important causes
      of infantile and traveler's diarrhea there is no licensed vaccine available for
      those at-risk. Our goal is to develop a safe, live attenuated ETEC vaccine. We
      used an attenuated E. coli strain (O157:H7, Delta-intimin, Stx1-neg, Stx2-neg) as
      a vector (ZCR533) to prepare two vaccine strains, one strain expressing
      colonization factor antigen I (ZCR533-CFA/I) and one strain expressing CFA/I and
      a detoxified heat-labile enterotoxin (ZCR533-CFA/I+LThK63) to deliver ETEC
      antigens to mucosal sites in BALB/c mice. Following intranasal and intragastric
      immunization with the vaccine strains, serum IgG and IgA antibodies were measured
      to the CFA/I antigen, however, only serum IgG antibodies were detected to the
      heat-labile enterotoxin. Intranasal administration of the vaccine strains induced
      respiratory and intestinal antibody responses to the CFA/I and LT antigens, while
      intragastric administration induced only intestinal antibody responses with no
      respiratory antibodies detected to the CFA/I and LT antigens. Mice immunized
      intranasally with the vaccine strains showed enhanced clearance of wild-type (wt)
      ETEC bacteria from the lungs. Mice immunized intranasally and intragastrically
      with the vaccine strains were protected from intestinal colonization following
      oral challenge with ETEC wt bacteria. Mice immunized intragastrically with the
      ZCR533-CFA/I+LThK63 vaccine strain had less fluid accumulate in their intestine
      following challenge with ETEC wt bacteria or with purified LT as compared to the
      sham mice indicating that the immunized mice were protected from LT-induced
      intestinal fluid accumulation. Thus, mice intragastrically immunized with the
      ZCR533-CFA/I+LThK63 vaccine strain were able to effectively neutralize the
      activity of the LT enterotoxin. However, no difference in intestinal fluid
      accumulation was detected in the mice immunized intranasally with the vaccine
      strain as compared to the sham mice as the immunized mice induced insufficient
      intestinal anti-LT antibody to neutralize the activity of the enterotoxin. These
      results show that our ETEC vaccine induced serum and mucosal antibody responses
      to CFA/I and LT after mucosal administration which then acted to protect the
      immunized mice against lung and intestinal colonization, as well as, intestinal
      fluid accumulation.

PMID- 23122618
TI  - An investigation of risk factors for foot-related lameness in a United Kingdom
      referral population of horses.
AB  - Lameness relating to the foot of the horse is common, but the majority of
      information concerning risk factors for injury is anecdotal. The objectives of
      this study were to investigate risk factors for foot-related pain in a referral
      population of horses, with particular reference to injury/disease of the
      podotrochlear apparatus (PTA), by comparison with the remainder of the clinic
      population. It was hypothesised that there would be an increased risk of foot
      pain associated with breed, work discipline, age, height and bodyweight (BW). A
      retrospective study of all horses examined at a referral centre between 2001 and
      2010 was performed using univariable and multivariable logistic regression
      analyses. There were 4618 horses investigated, 1132 of which had foot pain. There
      was increased risk of foot pain in multivariable analyses (all categories
      combined) in horses aged 6-9 and 10-15 years (OR = 1.60 and 1.72, respectively),
      compared with horses <6 years old, in show jumpers (OR = 1.44) compared with
      dressage horses, Thoroughbred cross-breeds (OR = 1.53) compared with Warmbloods
      and in horses with a BW:height ratio in the upper two quartiles (3.45-3.71 or
      >3.71; OR = 1.55 and 1.44, respectively), compared with the lowest quartile
      (<3.19). Racehorses had reduced risk for all types of foot pain combined (OR =
      0.13) compared with dressage horses. Risk factors for PTA injury were age (10-15
      years, OR = 2.12; >15 years, OR = 3.36, compared with <6 years old), BW:height
      ratio (>3.45-3.71 (OR = 2.75), >3.71 (OR = 2.06), compared with <3.19) and
      Thoroughbred cross-breed (OR = 1.73) compared with Warmbloods. Show jumpers had
      an increased risk of PTA and other injuries (OR = 2.29) when compared with
      dressage horses. Age, breed, work discipline and BW:height ratio influenced the
      risk of foot pain, but other factors probably also play a role.

PMID- 23122619
TI  - Liked, disliked and unseen forest attributes: relation to modes of viewing and
      cognitive constructs.
AB  - There is broad agreement that in determination of preferences the spatial
      configurations and content-based properties of the landscape interact with each
      other and with cognitive constructive. This interaction and how it is influenced
      by changes in landscape appearance was explored here in a site-specific context
      where 32 respondents took their own photos of liked and disliked attributes while
      walking a pre-defined trail of 2 km through a recreational forest landscape with
      extensive variation in landscape appearance and management regimes. Each
      respondent provided five photos of features that contributed positively to their
      landscape experiences and five that contributed negatively and recorded the
      location and reason in a photo-log, resulting in a total of 320 photos and photo
      log pairs. Photos of content-based attributes were more frequent than photos of
      the landscape's spatial organisation. Photos in the spatial configuration domain
      were dominated by liked attributes, while the content-based domain was dominated
      by disliked attributes. Subtle details and ephemera events constituted a large
      share of the captured content-based attributes, indicating that they are equally
      important for on-site experience of landscape character and attractiveness as
      larger landscape elements and their spatial organisation. Closer examination
      showed marked differences in the relative distribution of spatial and content
      based properties between forested and open landscape units. In forested units
      content-based attributes dominated, while in the open unit photos motivated by
      the spatial configurations in the implied space dominated. We concluded therefore
      that changes in depth of the perceptible space alter the relative importance of
      spatial and content-based properties for people's visual landscape perception,
      and thus the type of attributes that pass through the individual's perceptual and
      cognitive filters and become decisive in determining preferences.

PMID- 23122620
TI  - Modeling urban storm rainfall runoff from diverse underlying surfaces and
      application for control design in Beijing.
AB  - Managing storm rainfall runoff is paramount in semi-arid regions with urban
      development. In Beijing, pollution prevention in urban storm runoff and storm
      water utilization has been identified as the primary strategy for urban water
      management. In this paper, we sampled runoff during storm rainfall events and
      analyzed the concentration of chemical oxygen demand (COD), total suspended
      solids (TSS) and total phosphorus (TP) in the runoff. Furthermore, the first
      flush effect of storm rainfall from diverse underlying surfaces was also
      analyzed. With the Storm Water Management Model (SWMM), the different impervious
      rates of underlying surfaces during the storm runoff process were expressed. The
      removal rates of three typical pollutants and their interactions with
      precipitation and underlying surfaces were identified. From these rates, the
      scenarios regarding the urban storm runoff pollution loading from different
      designs of underlying previous rates were assessed with the SWMM. First flush
      effect analysis showed that the first 20% of the storm runoff should be
      discarded, which can help in utilizing the storm water resource. The results of
      this study suggest that the SWMM can express in detail the storm water pollution
      patterns from diverse underlying surfaces in Beijing, which significantly
      affected water quality. The scenario analysis demonstrated that impervious rate
      adjustment has the potential to reduce runoff peak and decrease pollution
      loading.

PMID- 23122621
TI  - Effects of rapid urban sprawl on urban forest carbon stocks: integrating remotely
      sensed, GIS and forest inventory data.
AB  - Research on the effects of urban sprawl on carbon stocks within urban forests can
      help support policy for sustainable urban design. This is particularly important
      given climate change and environmental deterioration as a result of rapid
      urbanization. The purpose of this study was to quantify the effects of urban
      sprawl on dynamics of forest carbon stock and density in Xiamen, a typical city
      experiencing rapid urbanization in China. Forest resource inventory data
      collected from 32,898 patches in 4 years (1972, 1988, 1996 and 2006), together
      with remotely sensed data (from 1988, 1996 and 2006), were used to investigate
      vegetation carbon densities and stocks in Xiamen, China. We classified the
      forests into four groups: (1) forest patches connected to construction land; (2)
      forest patches connected to farmland; (3) forest patches connected to both
      construction land and farmland and (4) close forest patches. Carbon stocks and
      densities of four different types of forest patches during different urbanization
      periods in three zones (urban core, suburb and exurb) were compared to assess the
      impact of human disturbance on forest carbon. In the urban core, the carbon stock
      and carbon density in all four forest patch types declined over the study period.
      In the suburbs, different urbanization processes influenced forest carbon density
      and carbon stock in all four forest patch types. Urban sprawl negatively affected
      the surrounding forests. In the exurbs, the carbon stock and carbon density in
      all four forest patch types tended to increase over the study period. The results
      revealed that human disturbance played the dominant role in influencing the
      carbon stock and density of forest patches close to the locations of human
      activities. In forest patches far away from the locations of human activities,
      natural forest regrowth was the dominant factor affecting carbon stock and
      density.

PMID- 23122622
TI  - Cephalometric analysis of modifications of the pharynx due to maxillo-mandibular
      advancement surgery in patients with obstructive sleep apnea.
AB  - Cephalometry has been used to measure hard and soft facial tissues, as well as
      the pharyngeal air space for the diagnosis of obstructive sleep apnea (OSA). The
      changes occurring in the pharynx due to maxillo-mandibular advancement (MMA) have
      not been established or quantified. The objective of this study was to identify
      the anatomical changes of the pharynx and of hard tissues that occur in patients
      with OSA after MMA. 19 patients with a polysomnographic diagnosis of OSA were
      submitted to cephalometric analysis before and 6 months after surgery in order to
      evaluate the changes produced by MMA in the pharynx and soft tissues.
      Cephalometry was standardized in order to obtain descriptive measurements of the
      dimensions of the airways, the position of the hyoid bone, and maxilla-mandibular
      relations. The modifications of the pharynx due to MMA showed a significant
      relation obtained by cephalometry. For each millimeter of maxillary and
      mandibular bone advancement there was a 0.76mm increase in the retropalatal
      region and a 1.2mm increase in the pharynx in the retrolingual region. In
      addition, MMA promoted a significant repositioning of the hyoid bone in the
      cranial direction.

PMID- 23122623
TI  - Liver metabolism in cardiac cachexia.

PMID- 23122624
TI  - Prenatal exposure to nicotine and impaired reading performance.
AB  - OBJECTIVE: To investigate whether prenatal exposure to nicotine has an impact on
      several reading skill outcomes in school age children. STUDY DESIGN: Using a
      longitudinal sample of 5119 school age children in the Avon Longitudinal Study of
      Parents and Children, this study investigated specific reading skill outcomes in
      the area of speed, fluency, accuracy, spelling, and comprehension in relation to
      prenatal nicotine exposure, after adjusting for potential mediators and
      confounders. Prenatal nicotine exposure was divided into 3 categories: high (>17
      mg per day), low (<=17 mg per day), and no exposure. RESULTS: We found that
      prenatal nicotine exposure was associated with increased risk of underperformance
      in specific reading skill outcomes after adjusting for potential mediators and
      confounders (P = .006). The effect of poor performance in decoding single words
      was most pronounced among children with prenatal exposure to high levels of
      nicotine in conjunction with a phonological deficit. Overall, the results showed
      that maternal smoking has moderate to large associations with delayed or
      decreased reading skills of children in the Longitudinal Study of Parents and
      Children. CONCLUSIONS: High prenatal nicotine exposure has a negative association
      with reading performance in school age children. In addition, modeling showed
      that environmental factors significantly moderated the interaction between
      prenatal nicotine exposure and reading skill outcomes.

PMID- 23122625
TI  - Selected trace metals (As, Cd and Hg) distribution and contamination in the
      coastal wetland sediment of the northern Beibu Gulf, South China Sea.
AB  - Contamination with As, Cd and Hg, their spatial and temporal distribution are
      reported from the coastal wetland sediments of the northern Beibu Gulf, South
      China Sea. The content of As, Cd, Hg and TOC in surface sediments is 8.1+/-5.8
      MUg g-1, 0.08+/-0.14MUg g-1, 0.034+/-0.028 MUg g-1 and 0.45+/-0.39%,
      respectively. The mean sedimentation rates are 0.93-1.37 cm year-1 during 1920s
      to 2008 determined by 210Pb and 137Cs dating in three cores. The vertical
      profiles of As, Cd and Hg content in the cores retrieved from Qin and Nanliu
      River estuaries show increasing trends during 1985-2008 due to anthropogenic
      impact caused by local economic development. Locally the surface sediments have
      potential ecological risk of As to benthos according to the NOAA sediment quality
      guidelines.

PMID- 23122626
TI  - Perfluorinated compounds in surficial sediments of the Ganges River and adjacent
      Sundarban mangrove wetland, India.
AB  - This study reports the first evidence of the quantification of two dominant
      perfluorinated compounds (PFCs), namely perfluorooctanesulfate (PFOS) and
      perfluorooctannoate (PFOA), in surface sediment samples (0-5 cm; n=13) from the
      Ganges (Hugli) River including Sundarban wetland, India using HPLC-MS/MS. The
      concentrations of PFOA exhibited a wide range of concentrations from <0.5 to
      14.09 ng/g dry wt, whereas the concentration of PFOS was always below the
      detection limit of <0.5 ng/g dry wt. A consistent enrichment of PFOA was recorded
      in all the five sites of Sundarban (mean value 11.61+/-1.86) whereas it was of
      moderate concentration or below the detection level in the seven sites along with
      the lower stretch of the Ganges (Hugli) River estuary (mean value 5.96 ng/g dry
      wt+/-5.36). Wastewater and untreated effluents are likely the major causes of
      accumulation of PFCs in sediments. The present paper could be used as baseline
      study to assess future monitoring programs of the ecosystem.

PMID- 23122627
TI  - Embryotoxic and genotoxic effects of heavy metals and pesticides on early life
      stages of Pacific oyster (Crassostrea gigas).
AB  - This study evaluated embryotoxicity and genotoxicity of two dissolved metals
      copper and cadmium (Cu and Cd) and two pesticides (metolachlor and irgarol)
      occurring in Arcachon Bay (SW France) in Pacific oyster (Crassostrea gigas)
      larvae and investigated the relationship between those two endpoints.
      Embryotoxicity was measured by calculating the percentage of abnormal D-shaped
      larvae and genotoxicity was evaluated with DNA strand breaks using the comet
      assay. After 24h exposure, significant increases of the percentage of abnormal D
      larvae and the DNA strand breaks were observed from 0.1 MUg L-1 for Cu, 10 MUg L
      1 for Cd and 0.01 MUg L-1 for both irgarol and metolachlor in comparison with the
      controls. A strong positive relationship between embryotoxicity and genotoxicity
      was recorded for Cu, Cd and metolachlor. The current study suggests that copper,
      irgarol and metolachlor can induce larval abnormalities and DNA damage in a
      population of exposed oysters at environmentally relevant concentrations.

PMID- 23122628
TI  - Environmental factors responsible for the incidence of antibiotic resistance
      genes in pristine Crassostrea virginica reefs.
AB  - The occurrence of tetracycline resistance (TRG) and integrase (INT) genes were
      monitored in Crassostrea virginica oyster reefs of three pristine creeks (SINERR,
      Georgia, USA). Their profiles revealed 85% similarity with the TRG/INT profiles
      observed in the adjacent to the SINERR and contaminated Altamaha River estuary
      (Barkovskii et al., 2010). The TRG/INT spectra and incidence frequencies
      corresponded to the source of oceanic input and to run-offs from creeks'
      watersheds. The highest incidence frequencies and concentrations were observed in
      oysters. TRG/INT incidences correlated positively (Spearman Rank=0.88), and
      negatively correlated (-0.63 to -0.79) with creek salinity, conductivity,
      dissolved solids, and temperature. Coliform incidence positively correlated with
      temperature, and not with the TRG/INT incidence. The Altamaha River estuary was
      the primary TRG/INT source for the reefs with contributions from creek's
      watersheds. TRG/INT were carried by non-coliforms with a preference for low-to
      temperate thermohaline environments coupled with bioaccumulation by oysters.

PMID- 23122629
TI  - Multidimensional assessment of vocal changes in benign vocal fold lesions after
      voice therapy.
AB  - OBJECTIVE: To evaluate through a multidimensional protocol voice changes after
      voice therapy in patients with benign vocal fold lesions. METHODS: 65 consecutive
      patients affected by benign vocal fold lesions were enrolled. Depending on
      videolaryngostroboscopy the patients were divided into 3 groups: 23 patients with
      Reinke's oedema, 22 patients with vocal fold cysts and 20 patients with
      gelatinous polyp. Each subject received 10 voice therapy sessions and was
      evaluated, before and after voice therapy, through a multidimensional protocol
      including videolaryngostroboscopy, perception, acoustics, aerodynamics and self
      rating by the patient. Data were compared using Wilcoxon signed-rank test.
      Kruskal-Wallis test was used to analyse the mean variation difference between the
      three groups of patients. Mann-Whitney test was used for post hoc analysis.
      RESULTS: Only in 11 cases videolaryngostroboscopy revealed an improvement of the
      initial pathology. However a significant improvement was observed in perceptual,
      acoustic and self-assessment ratings in the 3 groups of patients. In particular
      the parameters of G, R and A of the GIRBAS scale, and the noise to harmonic
      ratio, Jitter and shimmer scores improved after rehabilitation. A significant
      improvement of all the parameters of Voice Handicap Index after rehabilitation
      treatment was found. No significant difference among the three groups of patients
      was visible, except for self-assessment ratings. CONCLUSION: Voice therapy may
      provide a significant improvement in perceptual, acoustic and self-assessed voice
      quality in patients with benign glottal lesions. Utilization of voice therapy may
      allow some patients to avoid surgical intervention.

PMID- 23122630
TI  - Maternal obesity, gestational weight gain, and risk of asthma and atopic disease
      in offspring: a study within the Danish National Birth Cohort.
AB  - BACKGROUND: High pre-pregnancy body mass index (BMI) and excessive gestational
      weight gain (GWG) are suggested to influence risk of asthma and atopic disease in
      offspring. OBJECTIVE: We examined the effect of BMI and GWG on risk of asthma,
      wheezing, atopic eczema (AE), and hay fever in children during the first 7 years
      of life. METHODS: This was a cohort study of 38,874 mother-child pairs from the
      Danish National Birth Cohort (enrollment 1996-2002) with information from the
      16th week of pregnancy and at age 6 months, 18 months, and 7 years of the child.
      Odds ratios (ORs) with 95% CIs were calculated by logistic regression with
      adjustment for potential confounders. RESULTS: During the first 7 years of life,
      10.4% of children developed doctor-diagnosed asthma, 25.8% AE, and 4.6% hay
      fever. Maternal BMI and to a lesser extent GWG were associated with doctor
      diagnosed asthma ever. In particular, BMI>=35 (adjusted OR, 1.87; 95% CI, 0.95
      3.68) and GWG>=25 kg (adjusted OR, 1.97; 95% CI, 1.38-2.83) were associated with
      current severe asthma at age 7 years. Maternal BMI was also associated with
      wheezing in offspring, with the strongest association observed between BMI>=35
      and late-onset wheezing (adjusted OR, 1.87; 95% CI, 1.28-2.73). Maternal BMI and
      GWG were not associated with AE or hay fever. CONCLUSIONS: Maternal obesity
      during pregnancy was associated with increased risk of asthma and wheezing in
      offspring but not with AE and hay fever, suggesting that pathways may be
      nonallergic.

PMID- 23122631
TI  - Adult-onset manifestation of idiopathic T-cell lymphopenia due to a heterozygous
      RAG1 mutation.

PMID- 23122633
TI  - Towards an ontology for data quality in integrated chronic disease management: a
      realist review of the literature.
AB  - PURPOSE: Effective use of routine data to support integrated chronic disease
      management (CDM) and population health is dependent on underlying data quality
      (DQ) and, for cross system use of data, semantic interoperability. An ontological
      approach to DQ is a potential solution but research in this area is limited and
      fragmented. OBJECTIVE: Identify mechanisms, including ontologies, to manage DQ in
      integrated CDM and whether improved DQ will better measure health outcomes.
      METHODS: A realist review of English language studies (January 2001-March 2011)
      which addressed data quality, used ontology-based approaches and is relevant to
      CDM. RESULTS: We screened 245 papers, excluded 26 duplicates, 135 on abstract
      review and 31 on full-text review; leaving 61 papers for critical appraisal. Of
      the 33 papers that examined ontologies in chronic disease management, 13 defined
      data quality and 15 used ontologies for DQ. Most saw DQ as a multidimensional
      construct, the most used dimensions being completeness, accuracy, correctness,
      consistency and timeliness. The majority of studies reported tool design and
      development (80%), implementation (23%), and descriptive evaluations (15%).
      Ontological approaches were used to address semantic interoperability, decision
      support, flexibility of information management and integration/linkage, and
      complexity of information models. CONCLUSION: DQ lacks a consensus conceptual
      framework and definition. DQ and ontological research is relatively immature with
      little rigorous evaluation studies published. Ontology-based applications could
      support automated processes to address DQ and semantic interoperability in
      repositories of routinely collected data to deliver integrated CDM. We advocate
      moving to ontology-based design of information systems to enable more reliable
      use of routine data to measure health mechanisms and impacts.

PMID- 23122632
TI  - [Anal intraepithelial neoplasia].
AB  - Anal intraepithelial lesions are caused by chronic infection with oncogenic types
      of human papillomavirus. Their incidence and prevalence are increasing,
      especially among patients with HIV infection. Their natural history is not well
      known, but high-grade intraepithelial lesions seem to have an important risk to
      progress to squamous cell carcinoma. Their treatment can be achieved by many ways
      (surgery, coagulation, imiquimod, etc.) but there is a high rate of recurrent
      lesions. Pretherapeutic evaluation should benefit from high-resolution anoscopy.
      Periodic physical examination and anal cytology may probably be interesting for
      screening the disease among patients with risk factors. Vaccine against oncogenic
      types of papillomavirus may prevent the development of anal intraepithelial
      neoplasia. 

PMID- 23122634
TI  - Domain-specific control mechanisms for emotional and nonemotional conflict
      processing.
AB  - Recent neuroimaging studies suggest that the human brain activates dissociable
      cognitive control networks in response to conflicts arising within the cognitive
      and the affective domain. The present study tested the hypothesis that
      nonemotional and emotional conflict regulation can also be dissociated on a
      functional level. For that purpose, we examined the effects of a working memory
      and an emotional Go/Nogo task on cognitive control in an emotional and a
      nonemotional variant of the Stroop paradigm. The data confirmed the hypothesized
      dissociation: Working memory efforts selectively suppressed conflict regulation
      in the nonemotional Stroop task, while the demands of an emotional Go/Nogo task
      impaired only conflict regulation in the emotional Stroop task. We conclude that
      these findings support a modular architecture of cognitive control with domain
      specific conflict regulation processes.

PMID- 23122635
TI  - Executive well-being: updating of positive stimuli in working memory is
      associated with subjective well-being.
AB  - A growing literature shows that the ability to control affective information in
      working memory (WM) plays an important role in emotional functioning. Whereas
      most studies have focused on executive processes relating to emotion
      dysregulation and mood disorders, few, if any, have looked at such processes in
      association with happiness. In this study, we examined whether the ability to
      update positive and negative stimuli in WM (assessed with an affective n-back
      task) is related to the cognitive and affective components of subjective well
      being. Participants who were better at retaining and updating specifically
      positive (not negative) information in WM displayed higher levels of life
      satisfaction and affect balance, both at the trait level and in daily life. These
      results suggest that effective updating of positive information in WM may
      underlie happy people's ability to maintain and further enhance positive thoughts
      and emotions.

PMID- 23122636
TI  - Cocaine abuse or dependency and other pyschiatric disorders. Madrid study on dual
      pathology.
AB  - OBJECTIVES: The main objective of this study was to analyse the cocaine addict
      subgroup from the Madrid study of prevalence of dual disorders in community
      mental health and substance misuse services. MATERIAL AND METHODS: The sample
      consisted of 837 outpatients from Madrid, Spain. We compared 488 subjects who had
      a lifetime diagnosis of cocaine abuse or dependence, and 222 subjects who did not
      have a cocaine substance use disorder. We used the Mini International
      Neuropsychiatric Interview to evaluate axis I mental disorders, and the
      Personality Disorder Questionnaire to evaluate personality disorders. RESULTS:
      Almost three-quarters (73.4%) of cocaine addicts had a current dual disorder.
      Most prevalent were mood and anxiety disorders. Almost half (49.6%) had a
      personality disorder. Most of them (94.9%) had other substance use disorders.
      Cocaine addicts did not have higher prevalence rates of dual pathology than
      addicts with no cocaine abuse or dependence. Cocaine addicts were associated to a
      diagnosis of antisocial personality disorder, agoraphobia, and post-traumatic
      stress disorder, and they had an early age of onset of alcohol and cannabis use.
      CONCLUSIONS: Dual pathology is no higher in cocaine addicts in treatment than in
      addicts who do not use cocaine, however cocaine addicts started other drugs
      earlier, and were associated with specific mental disorders.

PMID- 23122637
TI  - Role of high-resolution ultrasound and PET/CT imaging for preoperative
      characterization of sentinel lymph nodes in cutaneous melanoma.
AB  - The purpose of our study was the comparison of high-resolution ultrasound (HRUS)
      and positron emission tomography combined with computerised tomography (PET/CT)
      in the preoperative characterization and identification of subclinical nodal
      metastases focusing on sentinel lymph nodes (SLN) in melanoma patients. Patients
      with cutaneous melanoma (CM) who received sentinel lymph node biopsy at the
      Department of Dermatology and Allergy, University of Bonn, between January 2009
      and January 2011 had been evaluated with a retrospective computer-aided search
      concerning preoperative staging procedures. A combination of PET/CT and HRUS had
      been performed preoperatively in 20 of 123 patients. A total of 59 SLNs had been
      removed in those 20 patients followed by histopathologic examination. HRUS
      correctly identified two of 17 positive SLNs whereas PET/CT imaging identified
      none. The sensitivity, specificity, positive predictive value (PPV) and negative
      predictive value (NPV) of HRUS were 11.8 % (95 % confidence interval [CI] = 3.3
      34.3), 100 % (95 % CI = 91.6-100.0), 100.0 % (95 % CI = 34.2-100.0), and 73.7 %
      (95 % CI = 61.0-83.3), respectively. On the basis of this limited study cohort,
      HRUS had a better value than PET/CT in preoperative identification of positive
      SLNs, suggesting a possible diagnostic superiority of HRUS in general
      characterization of peripheral nodal disease in CM.

PMID- 23122638
TI  - Four-dimensional speckle tracking for assessing improvement in left ventricular
      contractility after coronary angioplasty.
AB  - The objective of the study was to identify and quantify the potential improvement
      of left ventricular contractility after percutaneous transluminal coronary
      angioplasty (PTCA) using 4-dimensional (4D) speckle tracking echocardiography (4D
      STE). We investigated 41 patients with coronary disease by 4D STE pre- and 24
      hours postcoronarography with (n = 18) or without (n = 23) PTCA. The 4D STE
      visualizes in real time the myocardium strain on 2- and 4-chamber apical views
      and on 3 transverse views of the left ventricle. Average and total strain of the
      left ventricle were measured. Of the 18 PTCA patients, 15 showed significant
      increase in left ventricle mean (+15 +/- 6) and total strain (240 +/- 100), which
      corresponded to an increase of 93% +/- 55% from precoronarography, whereas the
      remainder showed no change. The total strain corresponded to 33% +/- 10% (before
      PTCA) and 59% +/- 11% (post PTCA) of the estimated normal strain for each
      patient. Strain improved in 70% of the segment downstream from the stent, and
      there was a negative correlation between the amplitude of the mean and total
      strain improvements after 24 hours and the mean and total strain values before
      PTCA. In the non-PTCA group, 21 of the 23 patients showed no changes in strain,
      whereas 2 showed improvement. The 4D STE showed significant improvements in left
      ventricular contractility in more than 70% of the areas downstream from the PTCA
      segment. This corresponded to an increase in the initial contractility by
      approximately 93% +/- 55%; however, the myocardium contractility remained
      approximately 59% of normal level. No changes were seen in patients without PTCA.

PMID- 23122639
TI  - Radial extracorporeal shock wave therapy (rESWT) induces new bone formation in
      vivo: results of an animal study in rabbits.
AB  - The aim of this study was to investigate if radial extracorporeal shock wave
      therapy (rESWT) induces new bone formation and to study the time course of ESWT
      induced osteogenesis. A total of 4000 impulses of radial shock waves (0.16
      mJ/mm2) were applied to one hind leg of 13 New Zealand white rabbits with the
      contralateral side used for control. Treatment was repeated after 7 days.
      Fluorochrome sequence labeling of new bone formation was performed by
      subcutaneous injection of tetracycline, calcein green, alizarin red and calcein
      blue. Animals were sacrificed 2 weeks (n = 4), 4 weeks (n = 4) and 6 weeks (n =
      5) after the first rESWT and bone sections were analyzed by fluorescence
      microscopy. Deposits of fluorochromes were classified and analyzed for
      significance with the Fisher exact test. rESWT significantly increased new bone
      formation at all time points over the 6-week study period. Intensity of
      ossification reached a peak after 4 weeks and declined at the end of the study.
      New bone formation was significantly higher and persisted longer at the ventral
      cortex, which was located in the direction to the shock wave device, compared
      with the dorsal cortex, emphasizing the dose-dependent process of ESWT-induced
      osteogenesis. No traumata, such as hemorrhage, periosteal detachment or
      microfractures, were observed by histologic and radiologic assessment. This is
      the first study demonstrating low-energy radial shock waves to induce new bone
      formation in vivo. Based on our results, repetition of ESWT in 6-week intervals
      can be recommended. Application to bone regions at increased fracture risk (e.g.,
      in osteoporosis) are possible clinical indications.

PMID- 23122640
TI  - An animal model allowing controlled receptor expression for molecular ultrasound
      imaging.
AB  - Reported in this study is an animal model system for evaluating targeted
      ultrasound (US) contrast agents binding using adenoviral (Ad) vectors to modulate
      cellular receptor expression. An Ad vector encoding an extracellular
      hemagglutinin (HA) epitope tag and a green fluorescent protein (GFP) reporter was
      used to regulate receptor expression. A low and high receptor density (in breast
      cancer tumor bearing mice) was achieved by varying the Ad dose with a low plaque
      forming unit (PFU) on day 1 and high PFU on day 2 of experimentation. Targeted US
      contrast agents, or microbubbles (MB), were created by conjugating either
      biotinylated anti-HA or IgG isotype control antibodies to the MB surface with
      biotin-streptavidin linkage. Targeted and control MBs were administered on both
      days of experimentation and contrast-enhanced US (CEUS) was performed on each
      mouse using MB flash destruction technique. Signal intensities from MBs retained
      within tumor vasculature were analyzed through a custom Matlab program. Results
      showed intratumoral enhancement attributable to targeted MB accumulation was
      significantly increased from the low Ad vector dosing and the high Ad vector
      dosing (p = 0.001). Control MBs showed no significant differences between day 1
      and day 2 imaging (p = 0.96). Additionally, targeted MBs showed a 10.5-fold
      increase in intratumoral image intensity on day 1 and an 18.8-fold increase in
      image intensity on day 2 compared with their control MB counterparts.

PMID- 23122641
TI  - Genetic associations between the ADHD symptom dimensions and Cloninger's
      temperament dimensions in adult twins.
AB  - Previous studies have identified phenotypic associations between Cloninger's
      temperament dimensions and the symptoms of attention deficit hyperactivity
      disorder (ADHD) in adults. However the underlying aetiology of these associations
      remains unclear. We investigate the extent to which genetic and environmental
      influences contribute to the relationship between temperament and ADHD, examining
      the ADHD symptoms of inattention (IA) and hyperactivity/impulsivity (HI)
      separately. Participants were 886 adult twin pairs aged 19-20 years. ADHD
      symptoms of IA and HI were measured using a DSM-IV based rating scale.
      Temperament was measured using Cloninger's Temperament and Character Inventory
      (TCI), across four dimensions: novelty seeking (NS), harm avoidance (HA), reward
      dependence (RD) and persistence (PS). The twin method was used to decompose
      phenotypic variance/covariance among these variables into genetic and
      environmental components. We found that NS was genetically associated with both
      ADHD symptom dimensions (IA and HI), but that HA was genetically associated with
      IA only. There was also some evidence of genetic association between PS, IA and
      HI. These findings suggest that unique profiles of temperament are genetically
      related to the two ADHD symptom dimensions in adults. Further work is now needed
      to elucidate the mechanisms that underlie both the combined and separate symptom
      factor domains of ADHD.

PMID- 23122642
TI  - Genetics in arterial calcification: lessons learned from rare diseases.
AB  - Arterial calcification significantly contributes to morbidity and mortality.
      Insight into the pathophysiological mechanisms contributing to arterial
      calcification has come from genetic studies on four rare monogenic disorders. The
      disease-causing molecular defects in generalized arterial calcification of
      infancy (GACI), pseudoxanthoma elasticum (PXE), calcification of joints and
      arteries (CALJA), and familial idiopathic basal ganglia calcification (IBGC) have
      been identified within recent years. Based on the similarities of GACI, PXE,
      CALJA, and IBGC, it can be speculated that the underlying disease genes-ENPP1,
      ABCC6, NT5E, and SLC20A2, respectively-drive a cohesive molecular pathophysiology
      system modulated by ATP metabolism, inorganic pyrophosphate, adenosine, and
      inorganic phosphate generation and functional activities.

PMID- 23122643
TI  - [Doughnut sign in thyroid lymphoma].

PMID- 23122644
TI  - Biotechnological opportunities with the beta-ketoadipate pathway.
AB  - The beta-ketoadipate pathway (beta-KAP) is an enzyme-mediated aryl-ring
      degradation sequence employed by a wide selection of soil bacteria and fungi to
      reconcile the conversion of many hazardous aromatic pollutants into benign
      metabolites of the tricarboxylic acid cycle (TCA), lipogenesis, and other
      anabolic processes. Recently determined catabolic sequences that incorporate the
      beta-KAP allow thorough mineralization of toxic priority pollutants including
      hazardous nitrophenols, organophosphates, and polychlorinated arenes and
      hydrocarbons. Novel investigations have applied the beta-KAP via oleaginous
      microorganisms to convert aromatic lignocellulosic waste into bio-oils that are
      suitable for biodiesel applications. These newly elucidated catabolic pathways
      and applications, reviewed here, provide exciting and unparalleled
      biotechnological opportunities for the future.

PMID- 23122645
TI  - Executive functions rehabilitation for schizophrenia: a critical systematic
      review.
AB  - BACKGROUND: Consistent evidences suggest that poor functional outcomes in
      schizophrenia are associated with deficits in executive functions (EF). As result
      cognitive training, remediation and/or rehabilitation (CR) programs have been
      developed and many theories, methods and approaches have emerged in support of
      them. This article presents a systematic review of randomized controlled trials
      (RCT), including EF rehabilitation interventions, with a focus on methodological
      issues and evidences of EF improvements. METHOD: Electronic databases (Medline,
      Web of Science, PsycINFO and Embase) were searched for articles on schizophrenia,
      EF and cognitive rehabilitation terms. The methodological quality of each article
      was measured by 5-point JADAD scale. RESULTS: A total of 184 articles were
      initially identified, but after exclusion criteria, 30 RCT remained in this
      review. A proportion of 23% of studies scored higher than 4 points in JADAD
      scale, 40% scored 3 points, 33% scored 2 points and one study scored only 1
      point. The average length of interventions was approximately 80 h distributed
      around 3.42 h/week. CONCLUSION: The reviewed articles corroborate the literature
      pointing that CR could be a promising therapeutic option for cognitive deficits
      in schizophrenia. In general, CR could improve cognitive domains and social
      adjustment either using computerized or paper-and-pencil programs. Additionally,
      CR combined with cognitive behavioral therapy and/or group sessions is
      particularly effective. In this paper, we also speculated and discussed optimal
      doses of treatment and the differences regarding modalities and approaches.

PMID- 23122646
TI  - [Questions--answers on the use of rivaroxaban for the treatment of venous
      thromboembolic disease].
AB  - Rivaroxaban is a direct oral anticoagulant targeting factor Xa. Efficacy and
      safety of rivaroxaban were evaluated through the phase 3 EINSTEIN program,
      consisting in three clinical trials regarding the treatment of deep vein
      thrombosis (EINSTEIN DVT), pulmonary embolism (EINSTEIN PE), and in secondary
      prevention after a first episode of venous thromboembolic disease (EISNTEIN EXT).
      Rivaroxaban was recently approved both by the European and the French Health
      agencies for the treatment of DVT and prevention of deep vein thrombosis
      recurrence. This report addresses the use of rivaroxaban in clinical practice in
      such indications.

PMID- 23122647
TI  - In vitro evaluation of the probiotic potential of Lactobacillus salivarius
      SMXD51.
AB  - Lactobacillus salivarius SMXD51 was previously isolated from the cecum of a
      Tunisian poultry and found to produce a bacteriocin-like substance highly active
      against the foodborne pathogen Campylobacter jejuni. The aim of this study was to
      examine some probiotic properties of the strain: acid and bile tolerance,
      capacity of adhesion, stimulation of immune defences (IL-6, IL-8, IL-10 and beta
      defensin 2), and modulation of the barrier integrity. The results showed that L.
      salivarius SMXD51 can tolerate gastrointestinal conditions (acid and bile),
      adhere to intestinal cells and stimulate the immune system. The bacterium
      strengthened the intestinal barrier functions through the increase of the
      transepithelial electrical resistance (TEER) and reinforcement of the F-actin
      cytoskeleton. One hour pretreatment with L. salivarius SMXD51 protected against
      Pseudomonas aeruginosa PAO1-induced decrease of TEER and damage of the F-actin
      cytoskeleton. Our results highlight that L. salivarius SMXD51 fulfils the
      principle requirements of an efficient probiotic and may be seen as a reliable
      candidate for further validation studies in chicken.

PMID- 23122648
TI  - E-learning initiatives in forensic interpretation: report on experiences from
      current projects and outlook.
AB  - This paper reports on the purpose, design, methodology and target audience of E
      learning courses in forensic interpretation offered by the authors since 2010,
      including practical experiences made throughout the implementation period of this
      project. This initiative was motivated by the fact that reporting results of
      forensic examinations in a logically correct and scientifically rigorous way is a
      daily challenge for any forensic practitioner. Indeed, interpretation of raw data
      and communication of findings in both written and oral statements are topics
      where knowledge and applied skills are needed. Although most forensic scientists
      hold educational records in traditional sciences, only few actually followed full
      courses that focussed on interpretation issues. Such courses should include
      foundational principles and methodology - including elements of forensic
      statistics - for the evaluation of forensic data in a way that is tailored to
      meet the needs of the criminal justice system. In order to help bridge this gap,
      the authors' initiative seeks to offer educational opportunities that allow
      practitioners to acquire knowledge and competence in the current approaches to
      the evaluation and interpretation of forensic findings. These cover, among other
      aspects, probabilistic reasoning (including Bayesian networks and other methods
      of forensic statistics, tools and software), case pre-assessment, skills in the
      oral and written communication of uncertainty, and the development of
      independence and self-confidence to solve practical inference problems. E
      learning was chosen as a general format because it helps to form a trans
      institutional online-community of practitioners from varying forensic disciplines
      and workfield experience such as reporting officers, (chief) scientists, forensic
      coordinators, but also lawyers who all can interact directly from their personal
      workplaces without consideration of distances, travel expenses or time schedules.
      In the authors' experience, the proposed learning initiative supports
      participants in developing their expertise and skills in forensic interpretation,
      but also offers an opportunity for the associated institutions and the forensic
      community to reinforce the development of a harmonized view with regard to
      interpretation across forensic disciplines, laboratories and judicial systems. 

PMID- 23122649
TI  - Protein group modification and synergy in the SUMO pathway as exemplified in DNA
      repair.
AB  - Protein modification by SUMO affects a wide range of protein substrates.
      Surprisingly, although SUMO pathway mutants display strong phenotypes, the
      function of individual SUMO modifications is often enigmatic, and SUMOylation
      defective mutants commonly lack notable phenotypes. Here, we use DNA double
      strand break repair as an example and show that DNA damage triggers a SUMOylation
      wave, leading to simultaneous multisite modifications of several repair proteins
      of the same pathway. Catalyzed by a DNA-bound SUMO ligase and triggered by single
      stranded DNA, SUMOylation stabilizes physical interactions between the proteins.
      Notably, only wholesale elimination of SUMOylation of several repair proteins
      significantly affects the homologous recombination pathway by considerably
      slowing down DNA repair. Thus, SUMO acts synergistically on several proteins, and
      individual modifications only add up to efficient repair. We propose that
      SUMOylation may thus often target a protein group rather than individual
      proteins, whereas localized modification enzymes and highly specific triggers
      ensure specificity.

PMID- 23122651
TI  - Changing mindsets in health policy and systems research.

PMID- 23122653
TI  - Alemtuzumab for multiple sclerosis.

PMID- 23122654
TI  - Knee kinematics in anterior cruciate ligament-substituting arthroplasty with or
      without the posterior cruciate ligament.
AB  - Few studies have compared functional kinematics in knees using identical
      prostheses with or without the posterior cruciate ligament (PCL). This study
      contrasted in vivo knee kinematics with an anterior cruciate ligament
      substituting arthroplasty with and without PCL retention. We hypothesized that
      knees without PCLs would exhibit less femoral posterior translation, and
      consequently less maximum knee flexion. Fifty-six knees were studied using
      dynamic radiography at least one year post-surgery, with twenty-seven knees
      retaining the PCL and twenty-nine knees having the PCL sacrificed. Consistent
      with our hypothesis, PCL-sacrificing knees showed more anterior femoral condylar
      positions. Contrary to our hypothesis, PCL-sacrificing knees demonstrated greater
      knee flexion during kneeling (122 degrees  versus 115 degrees ). Contracted PCLs
      in severely deformed knees likely were the cause of limited flexion in some
      retaining knees.

PMID- 23122655
TI  - The cementless anatomic Benoist Girard (ABG) II total hip arthroplasty: a minimum
      8-year follow-up study.
AB  - We have evaluated 90 consecutive primary cementless ABG II total hip
      replacements. The bearings combined metal-on-polyethylene in 64 hips, and alumina
      on-alumina in 26 hips. At the minimum 8-year follow-up, ten patients had died,
      seven had been lost to follow-up, two had undergone revision of either or both
      components, and 68 were still alive and had not been revised. With revision for
      any reason as the endpoint, the cumulative survival rate at 10years was 97.5%+/
      1.7%, and 98.7%+/-1.3% for the metal-back cup and the femoral component,
      respectively. No hip showed peri-acetabular osteolysis. The ABG II total hip
      arthroplasty has demonstrated favourable clinical and radiological outcomes as
      well as survival in the current series. Further follow-up is needed to confirm
      these mid-term results.

PMID- 23122656
TI  - Hematoma following primary total hip arthroplasty: a grave complication.
AB  - Hematoma following primary total hip arthroplasty (THA) can require a return to
      the operating room. The purpose of this study was to uncover risk factors for
      hematoma and how it affects the outcome of THA. This case-control study
      identified 38 patients requiring reoperation due to hematoma following THA
      between 2000 and 2007. The 38 patients were matched with 117 patients without
      hematoma. The mean follow-up was 4.1years (range, 2.1-9.6). Multivariate
      regression showed that blood loss, administration of fresh frozen plasma and
      Vitamin K, perioperative anticoagulation and hormonal therapy were independent
      predictors for hematoma formation. Chronic anticoagulation and autologous blood
      transfusion were independent risk factors for mortality. Hematoma itself was
      found to be an independent risk factor for adverse outcomes, increasing morbidity
      and mortality, despite adequate treatment.

PMID- 23122650
TI  - Alemtuzumab for patients with relapsing multiple sclerosis after disease
      modifying therapy: a randomised controlled phase 3 trial.
AB  - BACKGROUND: The anti-CD52 monoclonal antibody alemtuzumab reduces disease
      activity in previously untreated patients with relapsing-remitting multiple
      sclerosis. We aimed to assess efficacy and safety of alemtuzumab compared with
      interferon beta 1a in patients who have relapsed despite first-line treatment.
      METHODS: In our 2 year, rater-masked, randomised controlled phase 3 trial, we
      enrolled adults aged 18-55 years with relapsing-remitting multiple sclerosis and
      at least one relapse on interferon beta or glatiramer. Eligible participants were
      randomly allocated in a 1:2:2 ratio by an interactive voice response system,
      stratified by site, to receive subcutaneous interferon beta 1a 44 MUg,
      intravenous alemtuzumab 12 mg per day, or intravenous alemtuzumab 24 mg per day.
      Interferon beta 1a was given three-times per week and alemtuzumab was given once
      per day for 5 days at baseline and for 3 days at 12 months. The 24 mg per day
      group was discontinued to aid recruitment, but data are included for safety
      assessments. Coprimary endpoints were relapse rate and time to 6 month sustained
      accumulation of disability, comparing alemtuzumab 12 mg and interferon beta 1a in
      all patients who received at least one dose of study drug. This study is
      registered with ClinicalTrials.gov, number NCT00548405. FINDINGS: 202 (87%) of
      231 patients randomly allocated interferon beta 1a and 426 (98%) of 436 patients
      randomly allocated alemtuzumab 12 mg were included in the primary analyses. 104
      (51%) patients in the interferon beta 1a group relapsed (201 events) compared
      with 147 (35%) patients in the alemtuzumab group (236 events; rate ratio 0.51
      [95% CI 0.39-0.65]; p<0.0001), corresponding to a 49.4% improvement with
      alemtuzumab. 94 (47%) patients in the interferon beta 1a group were relapse-free
      at 2 years compared with 278 (65%) patients in the alemtuzumab group (p<0.0001).
      40 (20%) patients in the interferon beta 1a group had sustained accumulation of
      disability compared with 54 (13%) in the alemtuzumab group (hazard ratio 0.58
      [95% CI 0.38-0.87]; p=0.008), corresponding to a 42% improvement in the
      alemtuzumab group. For 435 patients allocated alemtuzumab 12 mg, 393 (90%) had
      infusion-associated reactions, 334 (77%) had infections (compared with 134 [66%]
      of 202 patients in the interferon beta 1a group) that were mostly mild-moderate
      with none fatal, 69 (16%) had thyroid disorders, and three (1%) had immune
      thrombocytopenia. INTERPRETATION: For patients with first-line treatment
      refractory relapsing-remitting multiple sclerosis, alemtuzumab could be used to
      reduce relapse rates and sustained accumulation of disability. Suitable risk
      management strategies allow for early identification of alemtuzumab's main
      adverse effect of secondary autoimmunity. FUNDING: Genzyme (Sanofi) and Bayer
      Schering Pharma.

PMID- 23122652
TI  - Alemtuzumab versus interferon beta 1a as first-line treatment for patients with
      relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial.
AB  - BACKGROUND: The anti-CD52 monoclonal antibody alemtuzumab reduced disease
      activity in a phase 2 trial of previously untreated patients with relapsing
      remitting multiple sclerosis. We aimed to assess efficacy and safety of first
      line alemtuzumab compared with interferon beta 1a in a phase 3 trial. METHODS: In
      our 2 year, rater-masked, randomised controlled phase 3 trial, we enrolled adults
      aged 18-50 years with previously untreated relapsing-remitting multiple
      sclerosis. Eligible participants were randomly allocated in a 2:1 ratio by an
      interactive voice response system, stratified by site, to receive intravenous
      alemtuzumab 12 mg per day or subcutaneous interferon beta 1a 44 MUg. Interferon
      beta 1a was given three-times per week and alemtuzumab was given once per day for
      5 days at baseline and once per day for 3 days at 12 months. Coprimary endpoints
      were relapse rate and time to 6 month sustained accumulation of disability in all
      patients who received at least one dose of study drug. This study is registered
      with ClinicalTrials.gov, number NCT00530348. FINDINGS: 187 (96%) of 195 patients
      randomly allocated interferon beta 1a and 376 (97%) of 386 patients randomly
      allocated alemtuzumab were included in the primary analyses. 75 (40%) patients in
      the interferon beta 1a group relapsed (122 events) compared with 82 (22%)
      patients in the alemtuzumab group (119 events; rate ratio 0.45 [95% CI 0.32
      0.63]; p<0.0001), corresponding to a 54.9% improvement with alemtuzumab. Based on
      Kaplan-Meier estimates, 59% of patients in the interferon beta 1a group were
      relapse-free at 2 years compared with 78% of patients in the alemtuzumab group
      (p<0.0001). 20 (11%) of patients in the interferon beta 1a group had sustained
      accumulation of disability compared with 30 (8%) in the alemtuzumab group (hazard
      ratio 0.70 [95% CI 0.40-1.23]; p=0.22). 338 (90%) of patients in the alemtuzumab
      group had infusion-associated reactions; 12 (3%) of which were regarded as
      serious. Infections, predominantly of mild or moderate severity, occurred in 253
      (67%) patients treated with alemtuzumab versus 85 (45%) patients treated with
      interferon beta 1a. 62 (16%) patients treated with alemtuzumab had herpes
      infections (predominantly cutaneous) compared with three (2%) patients treated
      with interferon beta 1a. By 24 months, 68 (18%) patients in the alemtuzumab group
      had thyroid-associated adverse events compared with 12 (6%) in the interferon
      beta 1a group, and three (1%) had immune thrombocytopenia compared with none in
      the interferon beta 1a group. Two patients in the alemtuzumab group developed
      thyroid papillary carcinoma. INTERPRETATION: Alemtuzumab's consistent safety
      profile and benefit in terms of reductions of relapse support its use for
      patients with previously untreated relapsing-remitting multiple sclerosis;
      however, benefit in terms of disability endpoints noted in previous trials was
      not observed here. FUNDING: Genzyme (Sanofi) and Bayer Schering Pharma.

PMID- 23122657
TI  - [Metastatic pulmonary calcifications in tertiary hyperparathyroidism].

PMID- 23122658
TI  - Acyclovir induced hypokalemia.

PMID- 23122659
TI  - Oral monosaccharide therapies to reverse renal and muscle hyposialylation in a
      mouse model of GNE myopathy.
AB  - GNE myopathy, previously termed hereditary inclusion body myopathy (HIBM), is an
      adult-onset neuromuscular disorder characterized by progressive muscle weakness.
      The disorder results from biallelic mutations in GNE, encoding UDP-N
      acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, the key enzyme of
      sialic acid synthesis. GNE myopathy, associated with impaired glycan sialylation,
      has no approved therapy. Here we test potential sialylation-increasing
      monosaccharides for their effectiveness in prophylaxis (at the embryonic and
      neonatal stages) and therapy (after the onset of symptoms) by evaluating renal
      and muscle hyposialylation in a knock-in mouse model (Gne p.M712T) of GNE
      myopathy. We demonstrate that oral mannosamine (ManN), but not sialic acid
      (Neu5Ac), mannose (Man), galactose (Gal), or glucosamine (GlcN), administered to
      pregnant female mice has a similar prophylactic effect on renal hyposialylation,
      pathology and neonatal survival of mutant offspring, as previously shown for N
      acetylmannosamine (ManNAc) therapy. ManN may be converted to ManNAc by a direct,
      yet unknown, pathway, or may act through another mode of action. The other sugars
      (Man, Gal, GlcN) may either not cross the placental barrier (Neu5Ac) and/or may
      not be able to directly increase sialylation. Because GNE myopathy patients will
      likely require treatment in adulthood after onset of symptoms, we also
      administered ManNAc (1 or 2g/kg/day for 12 weeks), Neu5Ac (2 g/kg/day for 12
      weeks), or ManN (2 g/kg/day for 6 weeks) in drinking water to 6 month old mutant
      Gne p.M712T mice. All three therapies markedly improved the muscle and renal
      hyposialylation, as evidenced by lectin histochemistry for overall sialylation
      status and immunoblotting of specific sialoproteins. These preclinical data
      strongly support further evaluation of oral ManNAc, Neu5Ac and ManN as therapy
      for GNE myopathy and conceivably for certain glomerular diseases with
      hyposialylation.

PMID- 23122661
TI  - [A rare cause of chronic dyspnea].

PMID- 23122660
TI  - The oscillating miRNA 959-964 cluster impacts Drosophila feeding time and other
      circadian outputs.
AB  - We sequenced Drosophila head RNA to identify a small set of miRNAs that undergo
      robust circadian cycling. We concentrated on a cluster of six miRNAs, mir-959
      964, all of which peak at about ZT12 or lights off. The cluster pri-miRNA is
      transcribed under bona fide circadian transcriptional control, and all six mature
      miRNAs have short half-lives, a requirement for cycling. A viable Gal4 knockin
      strain localizes prominent cluster miRNA expression to the adult head fat body.
      Analysis of cluster knockout and overexpression strains indicates that innate
      immunity, metabolism, and feeding behavior are under cluster miRNA regulation.
      Manipulation of food intake also affects the levels and timing of cluster miRNA
      transcription with no more than minor effects on the core circadian oscillator.
      These observations indicate a feedback circuit between feeding time and cluster
      miRNA expression function as well as a surprising role of posttranscriptional
      regulation in the circadian control of these phenotypes.

PMID- 23122662
TI  - [Paratesticular rhabdomyosarcoma in children: a scrotal emergency].
AB  - Paratesticular rhabdomyosarcoma is a rare and highly aggressive embryonal tumor
      in infancy and childhood. The tumor is intrascrotal, localized in the spermatic
      cord, the epididymis, or in the tunica vaginalis. Rhabdomyosarcoma represents 10%
      of testicular tumors of infancy. On physical examination, a painless scrotal
      tumefaction is observed. A surgical and pathological classification is used to
      group patients according to the extent of residual tumor after the initial
      surgical procedure: Intergroup Rhabdomyosarcoma Study classification (IRS).
      Multimodality therapy involving surgery, chemotherapy, and radiotherapy is
      necessary. Depending on the extent of disease and the staging group, the approach
      of treatment is different. The most important factors affecting treatment outcome
      are the stage, the pathological subtype of the tumor, and the age of the patient.
      Younger patients (<10 years) with a local tumor and with embryonal pathology have
      an excellent prognosis. We report the case of a 6-year-old boy admitted for a
      specialist consultation because of the recent appearance of a tumor in the right
      scrotum. On physical examination, a painless, solid, right scrotal mass was noted
      and the diagnosis of paratesticular rhabdomyosarcoma was made. This diagnosis can
      be suspected on physical and on ultrasound examinations, but only a pathological
      examination will confirm it. The authors discuss the therapeutic issues raised by
      this lesion and report one case of paratesticular rhabdomyosarcoma.

PMID- 23122664
TI  - Selecting the optimal candidate for adjuvant radiotherapy after radical
      prostatectomy for prostate cancer: a long-term survival analysis.
AB  - BACKGROUND: The role of adjuvant radiotherapy (ART) after radical prostatectomy
      (RP) on survival of patients with prostate cancer (PCa) is still controversial.
      OBJECTIVE: We tested the impact of ART on cancer-specific mortality (CSM) and
      overall mortality (OM) in PCa patients according to pathologic PCa features.
      DESIGN, SETTING, AND PARTICIPANTS: We evaluated 1049 PCa patients treated with RP
      and extended pelvic lymph node dissection alone or in combination with adjuvant
      treatments between 1998 and 2008. All patients had positive surgical margins
      and/or pT3/pT4 disease with or without positive lymph nodes. OUTCOME MEASUREMENTS
      AND STATISTICAL ANALYSIS: Cox regression analyses tested the relationship between
      pathologic characteristics and CSM rates. Independent predictors of survival were
      used to develop a novel risk score based on the number of risk factors. Finally,
      Cox regression models tested the relationship between ART and survival according
      to the number of risk factors. RESULTS AND LIMITATIONS: On multivariable
      analyses, only pathologic Gleason score >= 8, pT3b/T4 stage, and presence of
      positive lymph nodes represented independent predictors of CSM (all p <= 0.02).
      The cumulative number of these pathologic findings was used to develop a risk
      score, which was 0, 1, 2, and 3 in 43.6%, 22.1%, 20.7%, and 13.6% of patients,
      respectively. In patients sharing more than two mentioned predictors of CSM
      (primarily having a risk score of 0 or 1), ART did not significantly improve
      survival (all p >= 0.4). Conversely, in patients with a risk score >= 2, ART was
      associated with lower CSM and OM rates (all p=0.006). The observational nature of
      the cohort represents a limitation of the study. CONCLUSIONS: ART significantly
      improved survival only in patients with at least two of the following pathologic
      features at RP: Gleason score >= 8, pT3/pT4 disease, and positive lymph nodes.
      These patients represent the ideal candidates for ART after RP.

PMID- 23122665
TI  - Strengthening evidence for active surveillance for prostate cancer.

PMID- 23122666
TI  - Soluble epoxide hydrolase disruption as therapeutic target for wound healing.
AB  - BACKGROUND: Cytochrome P450 (CYP)-derived epoxyeicosatrienoic acids (EETs)
      possess angiogenic effects. However, the effect of CYP-derived EETs and soluble
      epoxide hydrolase (sEH) deletion on wound healing in vivo has not been rigorously
      investigated. In this study, we measured the effect of exogenous CYP-derived EETs
      and targeted disruption of sEH in an in vivo wound model. MATERIALS AND METHODS:
      Standardized full-thickness dermal wounds were created on the dorsum of mouse
      ears. Wound epithelialization was directly viewed and measured using intravital
      microscopy and computerized planimetry every second day until healing was
      complete. Wound sections were analyzed by immunostaining for metalloproteinase
      (MMP) 2, MMP7, MMP9, tissue inhibitor of metalloproteinases (TIMP) 1, and tumor
      necrosis factor (TNF) alpha on days 2, 4, and 12. RESULTS: Treatment with 11,12
      EETs, 14,15-EETs, and sEH deletion significantly accelerated wound closure. This
      effect was attenuated by the EET antagonist 14,15-epoxyeicosa-5(Z)-enoic acid
      (14,15-EEZE) in sEH(-/-) mice. Neither 11,12- nor 14,15-EETs caused significant
      alterations in MMP9 expression in wounds. In contrast, MMP2 and MMP7 were
      significantly upregulated in the EET-treated groups, whereas TIMP1 and TNF-alpha
      were downregulated. CONCLUSIONS: Collectively, these data demonstrated that
      potentiation of the CYP epoxy-genase pathway by either exogenous CYP-derived EETs
      or sEH deletion significantly accelerated wound epithelialization in vivo. This
      beneficial effect might be due to downregulation of TNF-alpha production and, to
      a lesser degree, to the release of MMPs and could be used as a viable angiogenic
      therapeutic strategy.

PMID- 23122667
TI  - Different sham procedures for rats in traumatic brain injury experiments induce
      corresponding increases in levels of trauma markers.
AB  - BACKGROUND: In traumatic brain injury animal models, sham or naive control groups
      are often used for the analysis of injured animals; however, the existence and/or
      significance of differences in the control groups has yet to be studied. In
      addition, recent controversies regarding the decompressive craniectomy trial in
      which decompressive craniectomies in patients with severe traumatic brain injury
      and refractory increased intracranial pressure remains unsettled. Although the
      report demonstrated that the procedure may result in less favorable long-term
      outcomes despite the decrease in intracranial pressure and shorter length of
      intensive care unit stay, the study has been criticized, and the debate is still
      inconclusive partly because of a lack of mechanistic explanation. We have
      recently discovered epithelial and endothelial tyrosine kinase (Etk) to exhibit
      upregulation after traumatic neural injury and will compare the effects of
      craniectomy procedure with those of other procedures inducing different levels of
      severity. MATERIALS AND METHODS: Four groups of rats receiving different
      procedures (controlled cortical impact, craniectomy, bicortical drilling, and
      unicortical drilling [UD]) were compared. Polymerase chain reaction, Western blot
      analysis, and immunoflorescence staining of Etk, S100, and glial fibrillary
      acidic protein levels were used to analyze the results and compare the different
      groups. RESULTS: Etk upregulation was statistically significant between
      craniectomy and UD groups. The level of change for glial fibrillary acidic
      protein and S100 was only significant when cortex was impacted. CONCLUSIONS: UD
      may be preferable as a sham control procedure over craniectomy or bicortical
      drilling. Increases in the expression of Etk in the craniectomy group suggest a
      possible mechanism by which unfavorable outcome occurs in patients receiving
      craniectomy procedures.

PMID- 23122668
TI  - Open reduction internal fixation versus hemiarthroplasty versus total hip
      arthroplasty in the elderly: a review of the National Surgical Quality
      Improvement Program database.
AB  - BACKGROUND: Total hip arthroplasty (THA), hemiarthroplasty (HA), and open
      reduction internal fixation (ORIF) are treatment options for femoral neck
      fractures. However, the optimal surgical treatment remains unclear. The present
      study aimed to describe the 30-d postoperative outcomes of THA, HA, and ORIF
      among patients aged >=65 y with femoral neck fractures within a national surgical
      database. MATERIALS AND METHODS: A retrospective analysis of the American College
      of Surgeons National Surgical Quality Improvement Program for January 2005
      through December 2009 was conducted. We included patients aged >=65 y who had
      undergone THA, HA, or ORIF for femoral neck fractures. We collected information
      on patient demographics, comorbidities, risk factors, and complication rates. A
      logistic regression model was used to assess the variation in overall morbidity
      and mortality after surgery. RESULTS: Overall, 3423 patients met the inclusion
      criteria: 674 underwent ORIF, 428 HA, and 2321 THA. Most patients were white
      (83.6%, n = 2862), female (64.4%, n = 2204), and >70 y old (78.4%, n = 2682). On
      adjusted multivariate analysis, no differences were found in the 30-d mortality
      rates among the ORIF, HA, and THA groups. Patients who underwent ORIF (odds ratio
      0.51, 95% confidence interval 0.27-0.94) and HA (odds ratio 0.43, 95% confidence
      interval 0.22-0.84) had a lower likelihood of developing respiratory
      complications compared with those who underwent THA. CONCLUSIONS: No differences
      were found in the 30-d mortality rates among the ORIF, HA, and THA groups. ORIF
      and HA resulted in a lower likelihood of developing respiratory complications
      than THA.

PMID- 23122669
TI  - Does dexmedetomidine affect intraoperative blood loss and clotting tests in
      pediatric adenotonsillectomy patients?
AB  - BACKGROUND: We hypothesize that dexmedetomidine (DEX), a selective alpha(2)
      adrenergic receptor agonist, may affect the intraoperative blood loss and
      clotting tests such as prothrombin time, activated partial thromboplastin time,
      and international normalized ratio in children undergoing adenotonsillectomy
      (ADT). METHODS: Sixty patients scheduled for elective ADT under general
      anesthesia. The patients were randomly assigned to receive either DEX 0.5 MUg/kg
      (group D) or placebo bolus (group C) with a total volume of 10 mL, 10 min before
      the induction of anesthesia. Mean arterial pressure (MAP), heart rate, blood
      loss, preoperatively and immediately after awakening clotting tests, agitation,
      sedation, visual analog scale, and analgesic requirement, were assessed and
      recorded. RESULTS: The postoperative hemoglobin was significantly lower than the
      preoperative value in both groups (P < 0.05). The postoperative agitation scale
      and analgesic requirement and visual analog scale at the 15th min were
      significantly lower in group D than those in group C (P < 0.05). Total blood loss
      and postoperative sedation score in group D was significantly higher than that in
      group C (P < 0.05). The postoperative prothrombin time, activated partial
      thromboplastin time, international normalized ratio tests between the groups,
      additionally pre-postoperative MAP, heart rate, and clotting tests were similar
      in each group. CONCLUSIONS: The premedication with DEX 0.5 MUg/kg decreased
      postoperative agitation, pain, and analgesic requirement without significant
      change in the clotting tests and MAP but increased bleeding slightly during ADT.

PMID- 23122670
TI  - Will there be progress?

PMID- 23122671
TI  - Decay-accelerating factor limits hemorrhage-instigated tissue injury and improves
      resuscitation clinical parameters.
AB  - BACKGROUND: Complement is invariably activated during trauma and contributes to
      tissue injury. Recombinant human decay-accelerating factor (DAF), a complement
      regulatory protein that inhibits both classical and alternative pathways,
      improves survival and reduces tissue damage in animal models of tissue injury.
      The extent to which DAF may facilitate resuscitation in hemorrhaged large animals
      is not known. METHODS: Male Yorkshire swine assigned to one of six groups were
      subjected to controlled, isobaric hemorrhage over 15 min to a target mean
      arterial pressure (MAP) of 35 mm Hg. Hypotension was maintained for 20 min
      followed by a bolus intravenous injection of DAF or vehicle followed by Hextend
      resuscitation. Animals were observed for 3 h after hypotensive Hextend
      resuscitation. Survival, blood chemistry, and physiological parameters were
      recorded. Additionally, tissue from lung, small intestine, liver, and kidney were
      subjected to histopathologic evaluation and tissue deposition of complement
      proteins was determined by immunohistochemistry, dot-blot, and Western blot
      analyses. RESULTS: Administration of DAF (25 MUg/kg) to animals subjected to
      hemorrhage prior to Hextend infusion significantly improved survival (73% versus
      27%); protected gut, lung, liver, and kidney tissue from damage; and resulted in
      reduced resuscitation fluid requirements when compared with animals subjected to
      hemorrhage and resuscitation with Hextend alone. Animals treated with a higher
      dose of DAF (50 MUg/kg) followed by Hextend fluid resuscitation did not
      experience the same benefit, suggesting a narrow therapeutic range for use of DAF
      as adjunct to Hextend fluid. CONCLUSION: DAF improved survival and reduced early
      Hextend fluid resuscitation requirements in swine subjected to hemorrhagic shock.
      These benefits are attributed to decreased complement deposition and limited
      organ damage.

PMID- 23122673
TI  - Accuracy of low-dose computed tomography (CT) for detecting and characterizing
      the most common CT-patterns of pulmonary disease.
AB  - PURPOSE: To assess the ability of low-dose CT to detect and characterize the most
      common CT patterns of pulmonary disease. METHODS AND MATERIALS: Sixty patients
      with nodules, consolidations or interstitial disease were scanned using a low
      dose (128 mm * 0.6 mm, 40 reference mAs, 120 kVp) and standard-dose CT protocol
      (150 reference mAs, 120 kVp). Two radiologists with 3 and 10 years of thoracic
      imaging experience searched both exams in consensus for the most commonly
      observed CT patterns according to the Fleischner Society criteria, which
      consisted of 46 different subgroups of ground-glass opacities, nodules,
      interstitial and airspace diseases. The standard of reference was established by
      consensus of a panel of two experienced chest radiologists (9 and 12 years of
      experience). RESULTS: The lung segments (1080) showed 813 nodules, 596 ground
      glass opacities, 74 airspace and 575 interstitial diseases and 64 normal
      segments. In particular, air-space disease and nodules were unaffected by the
      increase in noise. However, the sensitivity to detect ground-glass opacities,
      ground-glass nodules and interstitial opacities decreased significantly, from 89%
      to 77%, 86% to 68% and 91% to 71%, respectively (all p-values <0.00001). Using
      iterative reconstruction instead of the applied filtered back projection
      sensitivity for ground-glass nodules rose to the sensitivity of standard-dose CT
      in an additional phantom study. CONCLUSION: A low-dose CT of 40 mAs/120 kVp is
      feasible for detecting solid nodules, airspace, airways and pleural disease. For
      diagnosing pathologies consisting of ground-glass opacities or interstitial
      opacities, higher tube current or iterative reconstruction is required.

PMID- 23122674
TI  - Diagnostic performance of conventional diffusion weighted imaging and diffusion
      tensor imaging for the liver fibrosis and inflammation.
AB  - OBJECTIVE: To evaluate the diagnostic accuracy of liver apparent diffusion
      coefficient (ADC) measured with conventional diffusion-weighted imaging (CDI) and
      diffusion tensor imaging (DTI) for the diagnosis of liver fibrosis and
      inflammation. MATERIALS AND METHODS: Thirty-seven patients with histologic
      diagnosis of chronic viral hepatitis and 34 healthy volunteers were included in
      this prospective study. All patients and healthy volunteers were examined by 3T
      MRI. CDI and DTI were performed using a breath-hold single-shot echo-planar spin
      echo sequence with b factors of 0 and 1000 s/mm(2). ADCs were obtained with CDI
      and DTI. Histopathologically, fibrosis of the liver parenchyma was classified
      with the use of a 5-point scale (0-4) and inflammation was classified with use of
      a 4-point scale (0-3) in accordance with the METAVIR score. Quantitatively,
      signal intensity and the ADCs of the liver parenchyma were compared between
      patients stratified by fibrosis stage and inflammation grade. RESULTS: With a b
      factor of 1000 s/mm(2), the signal intensity of the cirrhotic livers was
      significantly higher than those of the normal volunteers. In addition, ADCs
      reconstructed from CDI and DTI of the patients were significantly lower than
      those of the normal volunteers. Liver ADC values inversely correlated with
      fibrosis and inflammation but there was only statistically significant for
      inflammatory grading. CDI performed better than DTI for the diagnosis of fibrosis
      and inflammation. CONCLUSION: ADC values measured with CDI and DTI may help in
      the detection of liver fibrosis. They may also give contributory to the
      inflammatory grading, particularly in distinguishing high from low grade.

PMID- 23122672
TI  - Postural tachycardia syndrome: a heterogeneous and multifactorial disorder.
AB  - Postural tachycardia syndrome (POTS) is defined by a heart rate increment of 30
      beats/min or more within 10 minutes of standing or head-up tilt in the absence of
      orthostatic hypotension; the standing heart rate is often 120 beats/min or
      higher. POTS manifests with symptoms of cerebral hypoperfusion and excessive
      sympathoexcitation. The pathophysiology of POTS is heterogeneous and includes
      impaired sympathetically mediated vasoconstriction, excessive sympathetic drive,
      volume dysregulation, and deconditioning. POTS is frequently included in the
      differential diagnosis of chronic unexplained symptoms, such as inappropriate
      sinus tachycardia, chronic fatigue, chronic dizziness, or unexplained spells in
      otherwise healthy young individuals. Many patients with POTS also report symptoms
      not attributable to orthostatic intolerance, including those of functional
      gastrointestinal or bladder disorders, chronic headache, fibromyalgia, and sleep
      disturbances. In many of these cases, cognitive and behavioral factors, somatic
      hypervigilance associated with anxiety, depression, and behavioral amplification
      contribute to symptom chronicity. The aims of evaluation in patients with POTS
      are to exclude cardiac causes of inappropriate tachycardia; elucidate, if
      possible, the most likely pathophysiologic basis of postural intolerance; assess
      for the presence of treatable autonomic neuropathies; exclude endocrine causes of
      a hyperadrenergic state; evaluate for cardiovascular deconditioning; and
      determine the contribution of emotional and behavioral factors to the patient's
      symptoms. Management of POTS includes avoidance of precipitating factors, volume
      expansion, physical countermaneuvers, exercise training, pharmacotherapy
      (fludrocortisone, midodrine, beta-blockers, and/or pyridostigmine), and
      behavioral-cognitive therapy. A literature search of PubMed for articles
      published from January 1, 1990, to June 15, 2012, was performed using the
      following terms (or combination of terms): POTS; postural tachycardia syndrome,
      orthostatic; orthostatic; syncope; sympathetic; baroreceptors;
      vestibulosympathetic; hypovolemia; visceral pain; chronic fatigue;
      deconditioning; headache; Chiari malformation; Ehlers-Danlos; emotion; amygdala;
      insula; anterior cingulate; periaqueductal gray; fludrocortisone; midodrine;
      propranolol; beta-adrenergic; and pyridostigmine. Studies were limited to those
      published in English. Other articles were identified from bibliographies of the
      retrieved articles.

PMID- 23122675
TI  - Validity of gradient-echo three-dimensional delayed gadolinium-enhanced magnetic
      resonance imaging of hip joint cartilage: a histologically controlled study.
AB  - OBJECTIVE: To validate gradient-echo three-dimensional (3D) delayed gadolinium
      enhanced magnetic resonance imaging of cartilage (dGEMRIC) by means of
      histological analyses in the assessment of hip joint cartilage. MATERIALS AND
      METHODS: Twenty-one femoral head specimens collected from 21 patients (7 males,
      14 females, mean age: 60.9 +/- 9.6 years; range: 37.6-77.3 years), who underwent
      total hip replacement for symptomatic hip joint osteoarthritis, underwent MRI and
      histological assessment. A region of 2 cm(2) at the weight-bearing area was
      marked with four pins to enable multi-planar MRI reformatting to be matched with
      histological sections. MRI was performed at 3T with a 3D double-echo steady-state
      (DESS) sequence for morphological cartilage assessment and 3D Volumetric
      Interpolated Breathhold Examination (VIBE) for T1(Gd) mapping. Histological
      sections were evaluated according to the Mankin score system. Total Mankin score,
      grade of toluidine staining (sensitive for glycosaminoglycan content) and a
      modified Mankin score classification system with four sub-groups of cartilage
      damage were correlated with MRI data. RESULTS: Spearman's rho correlation
      analyses revealed a statistically significant correlation between T1(Gd) mapping
      and histological analyses in all categories including total Mankin score (r=
      0.658, p-value <= 0.001), toluidine staining (r=-0.802, p-value<0.001) and
      modified Mankin score (r=-0.716, p-value<0.001). The correlation between
      morphological MRI and histological cartilage assessment was statistically
      significant but inferior to the biochemical cartilage MRI (r-values ranging from 
      0.411 to 0.525, p-values<0.001). CONCLUSIONS: Gradient-echo dGEMRIC is reliable
      while offering the unique features of high image resolution and 3D biochemically
      sensitive MRI for the assessment of early cartilage degeneration.

PMID- 23122676
TI  - Induction of rat facial nerve regeneration by functional collagen scaffolds.
AB  - Nerve conduit provides a promising strategy for nerve regeneration, and the
      proper microenvironment in the lumen could improve the regeneration. Our previous
      work had demonstrated that linear ordered collagen scaffold (LOCS) could
      effectively guide the oriented growth of axons. Laminin is known as an important
      nerve growth promoting factor and can facilitate the growth cone formation. In
      addition, ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic
      factor (BDNF) can effectively improve the nerve regeneration after nerve
      injuries. However, in practice, diffusion caused by the body fluids is the major
      obstacle in their applications. To retain CNTF or BDNF on the scaffolds, we
      produced collagen binding CNTF (CBD-CNTF), collagen binding BDNF (CBD-BDNF) and
      laminin binding CNTF (LBD-CNTF), laminin binding BDNF (LBD-BDNF) respectively. In
      this work, we developed laminin modified LOCS fibers (L * LOCS) by chemical cross
      linking LOCS fibers with laminin. Collagen binding or laminin binding
      neurotrophic factors were combined with LOCS or L * LOCS, and then filled them
      into the collagen nerve conduit. They were found to guide the ordered growth of
      axons, and improve the nerve functional recovery in the rat facial nerve
      transection model. The combination of CNTF and BDNF greatly enhanced the facial
      nerve regeneration and functional recovery.

PMID- 23122677
TI  - Brain-targeted delivery of protein using chitosan- and RVG peptide-conjugated,
      pluronic-based nano-carrier.
AB  - Brain-targeted delivery of drug or imaging agent is hard to achieve efficiently
      due to the infiltrative nature of the blood-brain barrier (BBB). Moreover,
      delivery of therapeutic proteins to brain tissue is further limited by the size
      and physic-chemical properties of proteins. In this work, we developed a chitosan
      conjugated Pluronic-based nano-carrier with a specific target peptide for the
      brain (rabies virus glycoprotein; RVG29) and applied for the protein delivery to
      the brain. The in-vivo brain accumulation of the nano-carrier in mice followed
      i.v injection was optically monitored with Cy5.5-conjugation to the nano-carrier,
      and the result showed that the Pluronic-based nano-carrier conjugated with both
      chitosan and the peptide was very efficient for the accumulation in brain tissue
      and was remarkably better than the nano-carrier conjugated with the peptide only.
      beta-galactosidase, a model protein, was also delivered and accumulated
      efficiently in the brain by loading in the nano-carrier, analyzed by the bio
      distribution of beta-galactosidase. The delivered protein in the brain also
      maintained its bioactivity. Therefore, RVG29- and chitosan-conjugated Pluronic
      based nano-carrier could be potentially useful for the diagnosis and therapy of
      brain diseases.

PMID- 23122678
TI  - Objective for 2015: 70% of treated and controlled hypertensive patients. Seven
      key points to reach this goal in practice. A joint call for action of the French
      League Against Hypertension and the French Society of Hypertension.
AB  - For the past 50 years, the implementation of therapeutic advances to the largest
      number of people has made it possible to have an exemplary reduction in
      cardiovascular mortality, contributing to extension of life expectancy observed
      in France. Nevertheless, such gains are fragile, and largely dependent on the
      quality of blood pressure control. The relative stagnation of blood pressure
      control in France for the last 5 years is potentially one of its early markers.
      The French League against Hypertension and the French Society of Hypertension,
      with the support of the French Ministry of Health, have decided to combine their
      efforts to provide a new impetus to management of this disease and to make blood
      pressure control a priority. An ambitious improvement of the percentage of
      controlled hypertensive patients from 50% to 70% in 2015 is targeted. To achieve
      this goal, a simplified decisional algorithm is proposed: seven key points
      dedicated to general practice are emphasized.

PMID- 23122679
TI  - Exposure to project-based Housing First is associated with reduced jail time and
      bookings.
AB  - BACKGROUND: Project-based Housing First (HF) programs provide immediate,
      permanent, low-barrier, nonabstinence-based supportive housing to chronically
      homeless people within a single housing project. Previous studies have shown
      project-based HF is associated with 6-month reductions in jail time (Larimer et
      al., 2009), and that people with criminal histories are able to maintain their
      housing in supportive housing, such as project-based HF (Malone, 2009; Tsai &
      Rosenheck, 2012). This study aimed to extend these findings to document the
      criminal histories of project-based HF residents and to test the associations
      among exposure to project-based HF, criminal histories and jail time over a 2
      year follow-up. METHODS: Participants (N = 95) were chronically homeless
      individuals with severe alcohol problems who moved into project-based HF.
      Measures included administrative data on criminal history, project-based HF
      exposure, and jail days and bookings for two-years prior to and subsequent to
      move into project-based HF. RESULTS: The majority of all past criminal
      convictions were misdemeanors (91.3%). Further, criminal convictions did not
      predict participants' housing retention in project-based HF. Months of project
      based HF exposure - not prior criminal histories - predicted significant
      decreases in jail days and bookings from the two years prior and subsequent to
      participants' move into HF. CONCLUSIONS: Findings suggest that participants'
      criminal histories primarily reflect "symptoms" of homelessness rather than
      threats to public safety. Further, the extent of participants' criminal histories
      was not associated with subsequent jail time or housing attrition. Although
      causation cannot be implied, these findings show that the amount of time spent in
      project-based HF is associated with decreased jail time for up to two years
      following initial HF exposure.

PMID- 23122680
TI  - Effect of pulse pressure on the predictability of stroke volume variation for
      fluid responsiveness in patients with coronary disease.
AB  - PURPOSE: We hypothesized that the predictability of stroke volume variation (SVV)
      on fluid responsiveness would be reduced in patients with coronary disease who
      have wide pulse pressure (PP). METHODS: Sixty-six patients undergoing coronary
      surgery were divided into 2 groups according to the PP measured 1 day before
      surgery: normal PP (n = 33, PP <= 60 mm Hg) or wide PP (n = 33, PP > 60 mm Hg).
      After applying mechanical ventilation, hemodynamic parameters (including SVV
      measured by the FloTrac/Vigileo system [Edwards Lifesciences, Irvine, Calif])
      were recorded before and 10 minutes after fluid replacement in a closed-chest
      condition. Prediction of fluid responsiveness was tested by calculating the area
      under the receiver operating characteristic curves. RESULTS: Twenty-one patients
      in the normal PP and 16 patients in the wide PP condition were fluid responders.
      The area under the receiver operating characteristic curves of SVV to predict
      fluid responsiveness were 0.808 (P = .022) and 0.609 (P = .288) in the normal PP
      and wide PP patients, respectively. In the normal PP condition, a SVV value of
      13% discriminated between fluid responders and nonresponders with a sensitivity
      of 76% and a specificity of 67%. CONCLUSIONS: In contrast to patients with normal
      PP, SVV does not predict fluid responsiveness in patients with coronary disease
      who have wide PP.

PMID- 23122681
TI  - [Validation of the dialectal Arabic version of Barratt's impulsivity scale, the
      BIS-11].
AB  - INTRODUCTION: Impulsivity is a symptom of several disorders such as personality
      disorder, bipolar disorder, suicidal behaviour, substance use disorders,
      schizophrenia...Forensic psychiatry is particularly concerned with impulsivity.
      It increases the risk of violence among clinical populations and figures in
      various instruments such as the HCR-20, the VRAG and the PCL-R to assess violence
      risk. It is one of many dimensions that can lead to aggressive behaviour among
      psychiatric patients. The Barratt Impulsiveness Scale (BIS), in its 11th version,
      is a 30-item self-report instrument that helps assessing impulsivity trait among
      normal and clinical populations. The BIS is the most commonly administered self
      assessment of impulsiveness. As of March 2009, there have been 551 citations of
      the BIS-11 among many publications. The purpose of the present study is to
      examine the psychometric properties of the Arabic translation of the BIS-11th
      version in a sample of the general population and to identify an eventual
      correlation between impulsivity and socio-demographic characteristics. PATIENTS
      AND METHODS: This is a prospective study conducted over a five-month period, from
      June to October 2010, and including 134 persons from the general population
      having provided their informed consent. The dialectal Arabic version was carried
      out by translation from English to dialectal Arabic followed by a back
      translation to English. Some questions were modified to be understood by a
      population with low education. After giving their verbal informed consent, the
      participants filled in the Arabic version of the BIS-11. For the illiterate,
      responses and quotations were performed by the interviewer. The persons were also
      asked to fill in socio-demographic data. Cronbach's coefficient was calculated,
      and then we assessed impulsivity prevalence and a correlation between demographic
      features and impulsivity scores. For the analyses, the statistical software SPSS
      11 was used. RESULTS: The sex ratio is 1.02. Most of the interviewed persons were
      20 to 49 years old. Around 25.4% of the sample were analphabets, 32.1% had
      primary education, 29.1% had secondary education and 13.4% were undergraduates.
      The Cronbach's alpha was respectively 0.66 for attention, 0.72 for motor
      impulsivity, 0.61 for lack of planning and 0.78 for total impulsivity. Factor
      analysis identified three factors explaining the total variance of 32.6%.
      Impulsivity prevalence was 9%. We did not find significant correlation between
      demographic features and impulsivity scores. DISCUSSION: Limits of the study:
      scale stability over time was not verified. This was due to the difficulty in re
      inviting the same persons to fulfil the scale a second time. Because no
      instrument for assessing exists in Arabic, comparison was not possible between
      the translated Barratt's scale and the reference. Our sample represents the
      general population. This choice was justified in order to study an eventual
      correlation between impulsiveness and socio-demographic characteristics. We must
      mention difficulties when asking persons with low education to complete the
      scale, what may have caused a poorer performance of the scale due to difficulties
      in understanding some questions. Moreover, we had chosen a non-clinical sample.
      The validation of the scale could be performed in a clinical population. The
      measure of internal consistency (Cronbach's alpha) fell within an acceptable
      range (0.61-0.78), suggesting that the Arabic version of the BIS-11 is reliable.
      Exploratory factor analysis of the current version identified three factors, but
      these factors differed from those of other translated versions. CONCLUSION: There
      is growing interest in the impulsivity concept. Forensic psychiatry is
      particularly concerned by impulsivity. In fact, it is related to psychiatric
      patients' violence. Impulsivity also reveals the problem of responsibility
      assessment in psychiatric expertise and the dangerousness of psychiatric
      patients. The Arabic version of the BIS-11 has a good apparent and internal
      consistency. This version could be useful in assessing psychiatric patient's
      dangerousness.

PMID- 23122682
TI  - Progestin treatment does not affect expression of cytokines, steroid receptors,
      oxytocin receptor, and cyclooxygenase 2 in fetal membranes and endometrium from
      pony mares at parturition.
AB  - In most mammalian species, progestins have a major function in maintaining
      pregnancy. In humans, the physiologic initiation of parturition bears
      similarities with inflammatory processes and anti-inflammatory effects of
      progestins have been suggested to postpone birth until term. To examine if
      comparable effects exist in the horse, mares were treated with the synthetic
      progestin altrenogest from day 280 of gestation until parturition (N = 5) or were
      left untreated as controls (N = 7). Tissue from the amnion (AMN), allantochorion
      (AC), and endometrium (EM) was collected at foaling and mRNA expression of
      interleukin (IL)-6 and -8, cyclooxygenase 2 (COX2), estrogen receptor (ER) alpha,
      progesterone receptor, and oxytocin receptor (OTR) was analyzed. Leukocytes,
      steroid receptors, COX2, and OTR were also investigated by histology and
      immunohistochemistry. Expression of mRNA for IL-6 was higher in AMN and EM versus
      AC (P < 0.01). Expression of IL-8 was higher in AMN than AC and EM (P < 0.001).
      Steroid receptors and OTR were highly expressed in EM but not in AMN and AC (P <
      0.001). Expression of COX2 was most pronounced in AC whereas IL expression was
      not upregulated in AC. No differences in mRNA expression existed between
      altrenogest-treated and control animals. Endometrial polymorphonuclear leukocytes
      were increased in altrenogest-treated mares. Epithelial cells of all tissues,
      except AC chorionic villi stained progesterone receptor-positive. Staining for ER
      was more pronounced in the amnion facing epithelium of the AC in altrenogest
      treated versus control animals (P < 0.01). In conclusion, COX2 is highly
      expressed in the AC. The fetal membranes thus might play a role in the onset of
      labor in the horse. Altrenogest did not affect gene expression in the AMN, AC,
      and EM but had localized effects on inflammatory cells and ER expression. No anti
      inflammatory effects of altrenogest in healthy, late pregnant pony mares could be
      detected.

PMID- 23122683
TI  - Restoration of corpus luteum angiogenesis in immature hypothyroid rdw rats after
      thyroxine treatment: morphologic and molecular evidence.
AB  - Thyroxine (T4) plus gonadotropins might stimulate ovarian follicular angiogenesis
      in immature infertile hypothyroid rdw rats by upregulating mRNA expression of
      major angiogenic factors. Development of growing corpus luteum (CL) is strongly
      related to angiogenesis and to morphofunctional development of microcirculation.
      Our aim was to investigate if T4 is involved in CL angiogenesis and in the
      activation of capillary cells and angiogenic factors after ovulation in a
      spontaneous model of hypothyroidism, the rdw rat. Rdw rats were treated with T4
      plus gonadotropins (equine chorionic gonadotropin plus human chorionic
      gonadotropin; eCG+hCG) or gonadotropins alone in order to evaluate the effects of
      T4 on early luteal angiogenesis, on microvascular cells and on expression of
      major growth factors which are involved in the regulation of angiogenesis. Wistar
      Imamichi rats treated with gonadotropins were used as controls. The ovaries were
      collected 4 days after hCG administration and analyzed using morphologic and
      molecular approaches. Thyroxine plus gonadotropins stimulated the growth of CLs
      and follicles as in controls, differently from rdw rats treated only with
      gonadotropins, in which CLs were not found and only small follicles, often
      atretic, could be recognized. In T4 plus gonadotropin-treated rdw rats CLs showed
      increased microvasculature, numerous activated capillaries characterized by
      sprouting and other angiogenic figures, and associated pericytes. Quantitative
      analysis revealed that the number of pericytes in T4 plus gonadotropin-treated
      rdw rats was comparable with that found in control rats and was significantly
      higher than that found in gonadotropin-treated rdw rats. The mRNA expression of
      vascular endothelial growth factor and basic fibroblast growth factor was
      significantly higher in control rats and in T4 plus gonadotropin-treated rdw rats
      than in gonadotropin-treated rdw rats. mRNA expression of tumor necrosis factor
      alpha, transforming growth factor beta, and epidermal growth factor did not show
      significant changes. Our data originally demonstrated that T4 promoted the growth
      of an active microcirculation in developing CLs of gonadotropin-primed
      hypothyroid rdw rats, mainly by inducing sprouting angiogenesis, pericyte
      recruitment, and upregulation of mRNA expression of vascular endothelial growth
      factor and basic fibroblast growth factor. In conclusion, we suggest that T4
      plays a key role in restoring luteal angiogenesis in ovaries of immature
      hypothyroid rdw rats.

PMID- 23122684
TI  - Progesterone-based strategies to induce ovulation in prepubertal Nellore heifers.
AB  - Four experiments were conducted to evaluate hormonal strategies to induce
      ovulation in Nellore heifers. In experiment 1, heifers (N = 1039) received a
      controlled internal drug release (CIDR) of fourth use (CIDR-4) on Day -12 or no
      CIDR (CIDR-0). The CIDR was removed on Day 0 in the CIDR-4 treatment, and estrus
      detection and AI were performed from Days 1 to 7. On Day 8, heifers not detected
      in estrus were evaluated for CL presence and received the same treatment again,
      followed by estrus detection and AI from Days 21 to 27. All heifers in
      experiments 2 (N = 896), 3 (N = 839), and 4 (N = 948) received the CIDR-4
      treatment on Day -12. In experiment 2, heifers were randomly assigned to a
      control group (no additional treatment) or to receive equine chorionic
      gonadotropin (eCG; 200 IU eCG im) on Day 0. In experiment 3, heifers received the
      same treatments as in experiment 2, or a treatment that included eCG and
      estradiol cypionate (ECP) (eCG+ECP; 200 IU im eCG plus 0.5 mg ECP im) on Day 0.
      In experiment 4, heifers received the treatments described in experiment 3 or
      only ECP (0.5 mg) on Day 0. In experiments 2 and 3, estrus detection and AI was
      performed from Days 1 to 7 and on Day 8, heifers not detected in estrus were
      evaluated for CL presence. In experiment 4, heifers were evaluated for presence
      of a CL between Days 10 and 14. In experiment 1 heifers treated with CIDR-4 had
      greater estrus detection, ovulation induction, and pregnancy rates than in the
      CIDR-0 group. In experiment 2, heifers treated with eCG had greater estrus
      detection, ovulation induction, and pregnancy rates in 7 days than heifers in the
      control group. In experiment 3, heifers treated with eCG+ECP had greater estrus
      detection, ovulation induction, and pregnancy rates than the control and eCG
      treatments. In experiment 4, ovulation induction was greater for heifers treated
      with eCG and eCG+ECP relative to control, but did not differ from the ECP
      treatment. In conclusion, the use of a CIDR of fourth use for 12 days and the
      addition of eCG and/or ECP at CIDR removal efficiently induced ovulation and
      increased pregnancy rates in prepubertal Nellore heifers.

PMID- 23122685
TI  - Expression of TRAIL in liver tissue from patients with different outcomes of HBV
      infection.
AB  - OBJECTIVES: Hepatitis B virus (HBV) infection triggers the production of TRAIL,
      suggesting that TRAIL may play a role in liver injury after HBV infection.
      However, it remains unclear whether TRAIL expression in liver tissue correlates
      with the extent of liver injury caused by HBV infection. The aim of this article
      was to investigate the correlation of TRAIL expression and disease severity.
      METHODS: Liver biopsy specimens were collected from 71 patients with different
      outcomes of HBV infection, including 25 cases of chronic hepatitis B (CHB), 18
      cases of severe hepatitis B (SHB), and 28 cases of liver cirrhosis (LC). Besides,
      specimens from 33 healthy individuals without detectable liver diseases were used
      as negative control (NC). The expression of TRAIL was measured by
      immunohistochemistry. RESULTS: Expression of TRAIL in the HBV-infected patients
      was higher than that in the NC (P<0.001). Among the patients, TRAIL expression in
      the ones with CHB was significantly higher than that in NC (P<0.001). However,
      there was no statistically significant difference between patients with SHB and
      NC or between the ones with LC and NC (P=0.067 and P=0.178, respectively).
      Moreover, TRAIL expression in patients with CHB was higher than that in patients
      with SHB or LC (P<0.001 for both), whereas no statistically significant
      difference was observed between patients with SHB and the ones with LC (P=0.511).
      CONCLUSION: TRAIL is involved in the inflammatory and immunoregulatory response
      after HBV infection. However, there was no significant correlation between
      expression of TRAIL and the extent of liver injury.

PMID- 23122686
TI  - [Assessment of an educational program for the prevention of healthcare-associated
      infections].
AB  - OBJECTIVE: To evaluate the effectiveness of an educational program for the
      prevention of healthcare-associated infections (HCAIs), based on Care Bundles.
      MATERIAL AND METHODS: A quasi-experimental study conducted in a university
      hospital from May 2011 to February 2012. An educational intervention (21 training
      sessions) was carried out in all Departments with the support of the contents in
      a leaflet, which included evidence-based Care Bundles for prevention of different
      HCAIs. The leaflet was also distributed through all Hospital Departments. We
      assessed the knowledge of health care workers (HCWs) as regards preventive
      measures before and after each training session using a self-administered
      questionnaire, and we studied the frequency of patients with HCAIs before and
      after the intervention. RESULTS: One-hundred-and-sixty-five out of 398 HCWs
      (41.5%) attended the training sessions. Their knowledge improved significantly,
      mainly in terms of: a) antimicrobial activity of alcohol-based solutions, b)
      preventive measures for cathether-associated urinary tract infections, and c)
      best place to insert a central venous catheter. These areas increased after
      training by 53.1, 29.7, and 28.2 points, respectively. There was a non
      significant decrease in the incidence of patients with HCAIs by multiresistant
      microorganisms, and a non-significant increase in the prevalence of patients with
      HCAIs. CONCLUSIONS: The educational program improved the knowledge of the HCWs
      about preventive measures for HCAIs, whereas the prevalence of patients with
      HCAIs did not show significant changes in the period of study.

PMID- 23122687
TI  - Hemoglobin and serum ferritin levels in women using copper-releasing or
      levonorgestrel-releasing intrauterine devices: a systematic review.
AB  - BACKGROUND: The use of intrauterine devices as a contraceptive method has been
      steadily growing in developing countries. Anemia in reproductive-age women is a
      growing concern in those settings. STUDY DESIGN: A systematic review of studies
      with measured hemoglobin and serum ferritin at baseline and after 1 year of use
      of copper intrauterine devices (IUDs) or a levonorgestrel-releasing intrauterine
      system (LNG IUS) was performed. RESULTS: Fourteen studies involving copper IUDs
      in nonanemic women and 4 studies in anemic women and 6 involving the LNG IUS met
      the criteria for the systematic review. Meta-analyses for hemoglobin changes
      showed significant decreases for users of copper IUDs and an increase for the LNG
      IUS, but with limited data. In general, ferritin levels followed the same
      pattern. CONCLUSION: Decreases in hemoglobin mean values in copper IUD users were
      not sufficient to induce anemia in previously nonanemic women. Women who are
      borderline anemic would likely benefit from using the LNG IUS.

PMID- 23122688
TI  - Denial of abortion care due to gestational age limits.

PMID- 23122689
TI  - Smart wearable systems: current status and future challenges.
AB  - OBJECTIVE: Extensive efforts have been made in both academia and industry in the
      research and development of smart wearable systems (SWS) for health monitoring
      (HM). Primarily influenced by skyrocketing healthcare costs and supported by
      recent technological advances in micro- and nanotechnologies, miniaturisation of
      sensors, and smart fabrics, the continuous advances in SWS will progressively
      change the landscape of healthcare by allowing individual management and
      continuous monitoring of a patient's health status. Consisting of various
      components and devices, ranging from sensors and actuators to multimedia devices,
      these systems support complex healthcare applications and enable low-cost
      wearable, non-invasive alternatives for continuous 24-h monitoring of health,
      activity, mobility, and mental status, both indoors and outdoors. Our objective
      has been to examine the current research in wearable to serve as references for
      researchers and provide perspectives for future research. METHODS: Herein, we
      review the current research and development of and the challenges facing SWS for
      HM, focusing on multi-parameter physiological sensor systems and activity and
      mobility measurement system designs that reliably measure mobility or vital signs
      and integrate real-time decision support processing for disease prevention,
      symptom detection, and diagnosis. For this literature review, we have chosen
      specific selection criteria to include papers in which wearable systems or
      devices are covered. RESULTS: We describe the state of the art in SWS and provide
      a survey of recent implementations of wearable health-care systems. We describe
      current issues, challenges, and prospects of SWS. CONCLUSION: We conclude by
      identifying the future challenges facing SWS for HM.

PMID- 23122690
TI  - Modeling and solving the dynamic patient admission scheduling problem under
      uncertainty.
AB  - OBJECTIVE: Our goal is to propose and solve a new formulation of the recently
      formalized patient admission scheduling problem, extending it by including
      several real-world features, such as the presence of emergency patients,
      uncertainty in the length of stay, and the possibility of delayed admissions.
      METHOD: We devised a metaheuristic approach that solves both the static
      (predictive) and the dynamic (daily) versions of this new problem, which is based
      on simulated annealing and a complex neighborhood structure. RESULTS: The quality
      of our metaheuristic approach is compared with an exact method based on integer
      linear programming. The main outcome is that our method is able to solve large
      cases (up to 4000 patients) in a reasonable time, whereas the exact method can
      solve only small/medium-size instances (up to 250 patients). For such datasets,
      the two methods obtain results at the same level of quality. In addition, the gap
      between our (dynamic) solver and the static one, which has all information
      available in advance, is only 4-5%. Finally, we propose (and publish on the web)
      a large set of new instances, and we discuss the impact of their features in the
      solution process. CONCLUSION: The metaheuristic approach proved to be a valid
      search method to solve dynamic problems in the healthcare domain.

PMID- 23122691
TI  - Periprosthetic atypical mycobacterial infection in breast implants: a new kid on
      the block!
AB  - INTRODUCTION: Breast augmentation is one of the most commonly performed cosmetic
      surgical procedures. Infection in the breast implant surgery can range from
      simple wound infection to periprosthetic infection usually with skin commensals
      such as staphylococci. However, with routine use of broad-spectrum antibiotics
      atypical mycobacterial infections are being increasingly reported. MATERIAL AND
      METHODS: We studied 12 cases of atypical mycobacterial breast implant infections
      over a period of 8 years from 2002 to 2010. Six of them were primarily operated
      at our centre and six referred from elsewhere after implant infection. Age range
      was 30-40 years and follow-up after secondary surgery ranged from 1 to 5 years.
      All patients were explanted and started on combination antibiotics namely,
      clarithromycin, gatifloxacillin and linezolid for 3 months. After a period of 3
      months, all patients underwent implant surgery again with the same antibiotic
      cover for 6 weeks. RESULT: All the secondary implant augmentations were
      successful. Organisms grown in primary culture were Mycobacterium fortuitum and
      M. chelonei. All patients were satisfied with the final breast form and size
      achieved. CONCLUSION: The possibility of an atypical mycobacterial infection
      should always be at the back of the mind of an alert surgeon to prevent a
      periprosthetic infection from compromising the final aesthetic result of a breast
      implant procedure. Diagnosed early and eradicated in time, the final result is
      not compromised.

PMID- 23122692
TI  - Double-barrel vascularised fibula graft in mandibular reconstruction: a 10-year
      experience with an algorithm.
AB  - BACKGROUND: This retrospective study aims to report an algorithm to assist
      surgeons in selecting different modes of the double-barrel vascularised fibula
      graft for mandibular reconstruction. METHODS: A total of 45 patients who
      underwent reconstruction of mandibular defects with different modes of the double
      barrel vascularised fibula graft were reviewed. Our algorithm for deciding on any
      one of the different modes for different mandibular defects is influenced by
      factors including history of radiotherapy, the length of mandibular body defect
      and the need to preserve the inferior mandibular border. Post-operative
      functional outcomes included diet type and speech, and aesthetic results gained
      at post-operative 2 years. Patients with implant-borne prosthetic teeth underwent
      assessment of their masticatory function. RESULTS: There were four modes of
      mandibular reconstruction according to our algorithm, which included double
      barrel vascularised fibula graft (n=21), partial double-barrel fibula graft
      (n=11), condylar prosthesis in combination with partial/double-barrel fibula
      graft (n=11), and double-barrel fibula onlay graft (n=2). Flap survival in all
      patients was 97.78%. Good occlusion, bony unions and wound closures were observed
      in 44 patients. Eleven patients received dental implantation in the transplanted
      fibula at post-operative 9-18th months. One patient wore removal partial
      dentures. For 11 patients with implant-borne prosthetic teeth, the average post
      operative ipsilateral occlusal force was 41.5+/-17.7% of the contralateral force.
      Good functional and aesthetic results were achieved in 38 patients with more than
      2 years of follow-up, including regular diet, normal speech and excellent or good
      appearance, especially for patients with dental rehabilitation. CONCLUSION: Good
      aesthetic and functional results can be achieved after dental rehabilitation by
      following our algorithm when choosing the different modes of double-barrel
      vascularised fibula graft for mandibular reconstruction.

PMID- 23122693
TI  - Lumbar posture and muscular activity while sitting during office work.
AB  - PURPOSE: Field study, cross-sectional study to measure the posture and sEMG of
      the lumbar spine during office work for a better understanding of the lumbar
      spine within such conditions. SCOPE: There is high incidence of low back pain in
      office workers. Currently there is little information about lumbar posture and
      the activity of lumbar muscles during extended office work. METHODS: Thirteen
      volunteers were examined for around 2h of their normal office work. Typical tasks
      were documented and synchronised to a portable long term measuring device for
      sEMG and posture examination. The correlation of lumbar spine posture and sEMG
      was tested statistically. RESULTS: The majority of time spent in office work was
      sedentary (82%). Only 5% of the measured time was undertaken in erect body
      position (standing or walking). The sEMG of the lumbar muscles under
      investigation was task dependent. A strong relation to lumbar spine posture was
      found within each task. The more the lumbar spine was flexed, the less there was
      activation of lumbar muscles (P < .01). Periods of very low or no activation of
      lumbar muscles accounted for about 30% of relaxed sitting postures. CONCLUSION:
      Because of very low activation of lumbar muscles while sitting, the load is
      transmitted by passive structures like ligaments and intervertebral discs. Due to
      the viscoelasticity of passive structures and low activation of lumbar muscles,
      the lumbar spine may incline into de-conditioning. This may be a reason for low
      back pain.

PMID- 23122695
TI  - Impact of hyperinsulinemia on the development of hypertension in normotensive,
      nondiabetic adults: a 4-year follow-up study.
AB  - BACKGROUND AND AIMS: This study aimed to investigate the association between
      baseline fasting insulin levels, changes in fasting insulin levels, and future
      development of hypertension in normotensive, non-diabetic, healthy adults.
      METHODS: We analyzed data from 11,123 adults, aged 20-65years, who had no history
      of hypertension or diabetes mellitus at a 2004 medical examination in a health
      promotion program and had attended a repeat examination in 2008. Subjects were
      divided into four groups according to baseline quartiles of fasting insulin and
      dichotomized fasting insulin levels at baseline and after 4years: low-low, low
      high, high-low, high-high. We also assessed whether the association differed
      between the younger (20-40years) and older subjects (41-65years). RESULTS: In
      four years, 1142 subjects (10.3%) developed hypertension. The odds ratio (OR) for
      the development for hypertension increased as the quartiles of baseline fasting
      insulin levels and changes in fasting insulin levels increased from the first to
      the fourth quartile (OR 1.15, 1.35, and 1.95 vs. 1.07, 1.22, and 1.41,
      respectively), after adjusting for multiple factors. The OR for hypertension was
      2.0-fold higher in the high-high group and 1.34-fold higher in the low-high group
      than in the low-low group. In comparing the results by age group, we found that
      these relationships were more prominent in younger subjects. CONCLUSION: High
      baseline and continuously increasing fasting insulin levels appeared to be
      independent determinants for the future development of hypertension during this 4
      year follow-up study in normotensive, non-diabetic, healthy adults.

PMID- 23122694
TI  - Genomic modulators of the immune response.
AB  - Our understanding of immunity has historically been informed by studying
      heritable mutations in both the adaptive and innate immune responses, including
      primary immunodeficiency and autoimmune diseases. Recent advances achieved
      through the application of genomic and epigenomic approaches are reshaping the
      study of immune dysfunction and opening up new avenues for therapeutic
      interventions. Moreover, applying genomic techniques to resolve functionally
      important genetic variation between individuals is providing new insights into
      immune function in health. This review describes progress in the study of rare
      variants and primary immunodeficiency diseases arising from whole-exome
      sequencing (WES), and discusses the application, success, and challenges of
      applying genome-wide association studies (GWAS) to disorders of immune function
      and how they may inform more rational use of therapeutics. In addition, the
      application of expression quantitative-trait mapping to immune phenotypes,
      progress in understanding MHC disease associations, and insights into epigenetic
      mechanisms at the interface of immunity and the environment are reviewed.

PMID- 23122696
TI  - Complete thoracoscopic ablation of the left atrium via the left chest for
      treatment of lone atrial fibrillation.
AB  - OBJECTIVE: We developed a new thoracoscopic ablation procedure for lone atrial
      fibrillation (AF) based on new endoscopic technology and the adoption of new
      types of energy. METHODS: Fifty-five patients with lone atrial fibrillation
      underwent this therapy. Patient age ranged from 30 to 81 years and there were 39
      men and 16 women. Of these patients, 38 had paroxysmal atrial fibrillation, 14
      had persistent atrial fibrillation, and 3 had longstanding atrial fibrillation.
      The procedure was performed on the beating heart through 3 ports in the left
      chest wall. Pulmonary vein isolation and ablation of the left atrium were
      achieved by bipolar radiofrequency ablation. Ganglionic plexus ablation was
      completed using the ablation pen. The left atrial appendage was excluded.
      RESULTS: Mean procedure duration was 106.6 +/- 42.8 minutes. No conversion to
      sternotomy or pacemaker implantation occurred and no patients died. Their
      hospital stay was 5.3 +/- 2.0 days with a mean follow-up of 12.6 +/- 2.2 months.
      Forty-nine of 55 patients (89.1%) patients were in sinus rhythm. Six patients
      could not maintain sinus rhythm. Thrombus in the left atrium and stenosis of the
      pulmonary vein were not found postoperatively. CONCLUSIONS: This less invasive
      procedure proved to be safe and presented optimistic outcomes, so it deserves to
      be promoted as a treatment for lone atrial fibrillation.

PMID- 23122697
TI  - Radial artery grafting in women improves 15-year survival.
AB  - OBJECTIVES: Radial artery (RA) grafting has a clear survival advantage after
      coronary artery bypass grafting (CABG) in studies with predominantly male
      populations, but the impact on women's long-term survival is unclear. We sought
      to determine if the reported long-term survival benefit of RA versus saphenous
      vein (SV) grafting in the general CABG population is valid for women. METHODS:
      Between 1995 and 2010, 1339 female patients were alive 30 days after primary,
      isolated CABG with left internal thoracic artery (LITA) and additional RA or SV
      conduits as needed. Patients were evaluated based on RA use: 332 patients had RA
      and 1007 patients had SV. Of these, 283 RA patients were matched to SV
      counterparts using a nonparsimonious propensity model based on 45 patient
      variables. RESULTS: Kaplan-Meier estimated survivals for the matched RA women at
      1, 5, 10, and 15 years were 99%, 93%, 80%, and 70% versus 97%, 87%, 72%, and 58%
      for the SV women (log rank, P = .018). For symptomatic patients, overall RA
      patency was 80%, which was not different from the LITA patency rate of 84% but
      was superior to the SV conduits patency rate of 56% (P < .001). CONCLUSIONS: In
      women undergoing CABG with LITA grafting, use of an RA graft improves survival
      compared with use of an SV graft.

PMID- 23122698
TI  - Bioprosthetic pulmonary valve replacement: contemporary analysis of a large,
      single-center series of 170 cases.
AB  - OBJECTIVE: The present study was designed to compare stented porcine and bovine
      pericardial valves used for pulmonary valve replacement to better define valve
      performance and postoperative quality of life. METHODS: A retrospective review of
      all patients who underwent pulmonary valve replacement with a stented
      bioprosthesis from 1992 to 2008 was conducted. The medical records, imaging
      results, and quality of life questionnaires were analyzed. Differences in
      reintervention by valve type were determined using Cox proportional hazards
      models, controlling for subject age. RESULTS: A total of 170 consecutive
      pulmonary valve replacements (73 stented porcine, group 1; 97 bovine pericardial,
      group 2) were reviewed. No significant differences were seen in patient age or
      implanted valve size between the groups. Surgical mortality was 1.2%. The median
      follow-up was 48.2 months and was longer for group 2. No significant difference
      was seen in the risk of reintervention by valve type (hazard ratio, 0.64; 95%
      confidence interval, 0.18-2.34; P = .51). After 39 months of follow-up, pulmonary
      stenosis and pulmonary insufficiency that was moderate or worse were more common
      in patients who had undergone pulmonary valve replacement at younger than 15
      years (pulmonary stenosis, 30.9% vs 10.0%, P = .003; pulmonary insufficiency,
      46.2% vs 3.8%, P < .001), regardless of valve type. All patients performed well
      mentally and physically on the quality of life surveys. CONCLUSIONS: The present
      large series of stented bioprosthetic pulmonary valve replacements has
      demonstrated good results, particularly in adults, at intermediate follow-up.
      Freedom from reintervention was similar for the porcine and pericardial valves,
      and our finding did not clearly demonstrate the superiority of 1 type of valve.
      However, the stented bioprosthetic valves were less durable in younger patients.

PMID- 23122699
TI  - Differential expression of endocannabinoid system in normal and preeclamptic
      placentas: effects on nitric oxide synthesis.
AB  - Anandamide (AEA) is a lipid mediator that participates in the regulation of
      several reproductive functions. This study investigated the endocannabinoid
      system in normal (NP) and preeclamptic (PE) placentas, and analyzed the potential
      functional role of AEA in the regulation of nitric oxide synthesis. The protein
      expression and localization of NAPE-PLD, FAAH and CB1 receptor were analyzed in
      normal and preeclamptic pregnancies using immunoblotting and
      immunohistochemistry. NAPE-PLD expression was shown to be significantly higher (p
      < 0.05) in PE tissues than in NP. In contrast, a decrease in FAAH protein (p <
      0.001) was detected in placentas collected from women with preeclampsia. Both
      enzymes were mainly located in the syncytiotrophoblasts from normal and
      preeclamptic tissues. No differences were seen in CB1 receptor from both groups
      of placental villous. Exogenous and endogenous AEA significantly increased NOS
      activity. Although pre-incubation with AM251 (CB1 antagonist) had no effect, co
      incubation with both AEA and AM251 diminished NOS activity from normal term
      placentas. We observed increased NOS activity in placental villous from women
      with preeclampsia compared with normotensive pregnant women. Furthermore, NOS
      activity from preeclamptic tissues was diminished by co-treatment with AM251,
      illustrating that the NO levels could be modulated by AEA. These data suggest
      that AEA may be one of the factors involved in the regulation of NOS activity in
      normal and preeclamptic placental villous. Interestingly, the differential
      expression of NAPE-PLD and FAAH suggests that AEA could play an important role in
      the pathophysiology of PE.

PMID- 23122700
TI  - Endothelial eNOS/arginase imbalance contributes to vascular dysfunction in IUGR
      umbilical and placental vessels.
AB  - Placental vascular tone is critically influenced by nitric oxide (NO) derived
      from endothelial NO synthase (eNOS) activity. Placental vessels from pregnancies
      complicated with intrauterine growth restriction present altered NOS-dependent
      vasodilation. Arginase-2 competes with eNOS for l-arginine and counteracts the
      NOS-dependent relaxation in umbilical vessels from normal pregnancies. However
      there is no data regarding the contribution of arginase activity on the impaired
      endothelial function in IUGR placenta. We studied whether arginase-2 participates
      in IUGR-related placental vascular dysfunction counteracting eNOS-dependent
      relaxation, and the regulation of arginase-2 and eNOS expression in endothelial
      cells from IUGR umbilical arteries (HUAEC) and veins (HUVEC). In IUGR-derived
      umbilical arteries (UA) and veins (UV), and chorionic arteries (CA), NOS
      dependent vasoactive response in the presence and absence of BEC (arginase
      inhibitor) was studied. Protein levels of eNOS (total and Ser(1177)-P-eNOS),
      arginase-2 and arginase activity were determined in IUGR HUAEC and HUVEC. In IUGR
      vessels eNOS-dependent relaxation was reduced, being improved by BEC. This effect
      was higher in arteries than veins, and in chorionic compared with umbilical
      vessels. In cultured IUGR endothelial cells, arginase-2 protein expression and
      activity were increased in HUVEC, without changes in HUAEC. In IUGR-derived
      endothelium there was a generalized reduction in the in vitro eNOS activation
      (Ser(1177)-P-eNOS/eNOS), and therefore a decreased eNOS/arginase activity ratio.
      Here we provide ex vivo and in vitro evidence for a vascular role of arginase
      throughout placental vasculature, negatively controlling NOS activity. This
      effect seems to be crucial in the pathophysiology of endothelial dysfunction
      present in IUGR feto-placental vessels.

PMID- 23122701
TI  - Neural control of rising and falling tones in Mandarin speakers who stutter.
AB  - Neural control of rising and falling tones in Mandarin people who stutter (PWS)
      was examined by comparing with that which occurs in fluent speakers [Howell,
      Jiang, Peng, and Lu (2012). Neural control of fundamental frequency rise and fall
      in Mandarin tones. Brain and Language, 121(1), 35-46]. Nine PWS and nine controls
      were scanned. Functional connectivity analysis showed that the connections
      between the insula and LMC and between the LMC and the putamen differed
      significantly between PWS and fluent speakers during both rising and falling
      tones. The connection between the insula and the brainstem differed between PWS
      and fluent speakers only during the falling tone. These results indicated the
      neural control for the rising tone and the falling tone are affected in PWS.
      Moreover, whilst both rising and falling tones were affected in PWS, falling-tone
      control appeared to be affected more.

PMID- 23122702
TI  - Pseudoscardovia suis gen. nov., sp. nov., a new member of the family
      Bifidobacteriaceae isolated from the digestive tract of wild pigs (Sus scrofa).
AB  - Seventeen fructose-6-phosphate phosphoketolase-positive bacterial strains were
      isolated from the digestive tract of wild pigs (Sus scrofa). Most of them were
      identified as Bifidobacterium boum according to sequences of 16S rRNA gene. Two
      strains isolated from the small intestine content had unusual morphology of cells
      in comparison with bifidobacteria. Cells growing in liquid anaerobic media were
      regular shaped rods arranged mostly in pairs. These isolates showed relatively
      low 16S rRNA gene sequence similarities (maximum identity of 94%) to members of
      the family Bifidobacteriaceae. Nevertheless, phylogenetic analyses of 16S rRNA,
      hsp60 and xfp gene sequences revealed that these strains are more related to
      recently described Neoscardovia, Aeriscardovia and other scardovial genera, than
      to Bifidobacterium species. Partial gene sequences of other phylogenetic markers
      showed low (65.8-89.5%) similarities to genome sequences of bifidobacteria and
      Gardnerella vaginalis. The major fatty acids detected in cells of the
      representative strain DPTE4(T) were C(16:0), C(18:1), C(14:0). The peptidoglycan
      type of the DPTE4(T) strain was A3betal-Orn(l-Lys)-l-Ser(l-Ala)-l-Ala(2). Polar
      lipid analysis revealed two phosphoglycolipids and phospholipids, a glycolipid
      and diphosphatidylglycerol. The results of phylogenetic, genotypic and phenotypic
      analyses support the proposal of a novel taxa, Pseudoscardovia suis gen. nov.,
      sp. nov. (type strain=DPTE4(T)=DSM 24744(T)=CCM 7942(T)).

PMID- 23122703
TI  - Electrosynthesis of an imidazole derivative and its application as a bifunctional
      electrocatalyst for simultaneous determination of ascorbic acid, adrenaline,
      acetaminophen, and tryptophan at a multi-wall carbon nanotubes modified electrode
      surface.
AB  - In this research, the electrosynthesis of 4-(1H-benzo[d]imidazol-2-ylthio)-5
      methylbenze-1,2-diol (as an imidazole derivative) is reported. An imidazole
      derivative multi-wall carbon nanotube modified glassy carbon electrode (IMWCNT
      GCE) was constructed and used as an excellent bifunctional electrocatalyst for
      oxidation of ascorbic acid (AA) and adrenaline (AD). Cyclic voltammetry was used
      to calculate the surface electron transfer rate constant, k(s), and the electron
      transfer coefficient, alpha, for the electron transfer between MWCNT-GCE and the
      electrodeposited imidazole derivative. The kinetic parameters such as the
      electron transfer coefficient, alpha, and the heterogeneous rate constant, k',
      for the oxidation of AA and AD at the IMWCNT-GCE surface were estimated. The
      modified electrode was found quite effective for the simultaneous determination
      of AA, AD, acetaminophen (AC), and tryptophan (Trp) in a mixture solution. The
      detection limits of AA and AD were calculated as 0.96 MUM and 0.38 MUM,
      respectively. Finally, IMWCNT-GCE was satisfactorily used for the determination
      of AA, AD, and AC in pharmaceutical samples.

PMID- 23122704
TI  - Porous silicon biosensor: current status.
AB  - Biosensing technologies cater to modern day diagnostics and point of care multi
      specialty clinics, hospitals and laboratories. Biosensors aggregate the
      sensitivity of detection methodologies and constitutional selectivity of
      biomolecules. Endeavors to develop highly sensitive, fast, stable and low cost
      biosensors have been made possible by extensive and arduous research. Immense
      research work is going on for detection of molecules using various materials as
      immobilization substrate and sensing elements. Amongst materials being used as
      bio-sensing substrates, nano-porous silicon (PS) has amassed attention and gained
      popularity in recent years. It has captivating and tunable features like ease of
      fabrication, special optico-physico properties, tailored morphological structure
      and versatile surface chemistry enhancing its prospects as transducer for
      fabricating biosensors. The present review describes the fabrication of PS and
      its biosensing capabilities for detection of various analytes including, but not
      limited to, glucose, DNA, antibodies, bacteria and viruses. Attention has been
      consecrated on the various methodologies such as electrical, electrochemical,
      optical and label free techniques along with the performances of these
      biosensors. It concludes with some future prospects and challenges of PS based
      biosensors.

PMID- 23122705
TI  - Histogenetic relations between keratoameloblastoma and solid variant of
      odontogenic keratocyst.

PMID- 23122706
TI  - [Disseminated infection due to Geotrichum capitatum].

PMID- 23122707
TI  - Prevention of seroma formation with TissuGlu(r) surgical adhesive in a canine
      abdominoplasty model: long term clinical and histologic studies.
AB  - BACKGROUND: Seroma formation is a common postoperative complication following
      many surgical procedures including abdominoplasty. Recently, a lysine-derived
      urethane (LDU) surgical adhesive was shown to prevent seroma formation in short
      term studies in a canine model of abdominoplasty. This current study evaluates
      efficacy of the adhesive (TissuGlu(r), Cohera Medical, Inc.) in the same model at
      longer time points, and examines the histological tissue response to extended
      exposure to the adhesive. MATERIALS AND METHODS: Bilateral subcutaneous pockets
      were created in the ventrolateral abdominal wall and additional tissue damage was
      inflicted using electrocautery. On one side, the tissue layers were treated with
      the adhesive prior to closure, whereas the control side received no treatment
      prior to standard closure of the incision. Seroma fluid accumulation was measured
      and histologic analysis was performed at 3 and 12 weeks. RESULTS: Seroma
      formation (mean+/-SD, 690+/-870 ml; median volume of 348.5 ml) was observed on
      the control side, whereas the treated side had adherence between the tissue
      layers, and minimal if any fluid accumulation (mean+/-SD, 44+/-53 ml; median
      volume of 15 ml) (p<0.01) (n=8) at 3 week necropsy. In animals survived to 12
      weeks, two of the four control sides required aspiration of serous fluid, and
      dead space persisted for the entirety of the study in one animal. For the
      adhesive treated sites, none of the four animals showed signs of seroma at
      euthanasia, although serial aspiration was performed in one treatment site within
      the first month and resulted in resolution of the process. The adhesive was
      detected in the surgical site at 3 and 12 weeks, and independent histological
      analysis found it to be a non-irritant compared to control (no treatment).
      CONCLUSIONS: Long term evaluation of TissuGlu(r) Surgical Adhesive showed that it
      is capable of preventing the formation of seroma in this canine abdominoplasty
      model, indicating that it may be of clinical benefit in the prevention of seroma
      formation in patients undergoing abdominoplasty.

PMID- 23122708
TI  - Test-retest reliability and stability of N400 effects in a word-pair semantic
      priming paradigm.
AB  - OBJECTIVE: Elicited by any meaningful stimulus, the N400 event-related potential
      (ERP) component is reduced when the stimulus is related to a preceding one. This
      N400 semantic priming effect has been used to probe abnormal semantic
      relationship processing in clinical disorders, and suggested as a possible
      biomarker for treatment studies. Validating N400 semantic priming effects as a
      clinical biomarker requires characterizing their test-retest reliability.
      METHODS: We assessed test-retest reliability of N400 semantic priming in 16
      healthy adults who viewed the same related and unrelated prime-target word pairs
      in two sessions one week apart. RESULTS: As expected, N400 amplitudes were
      smaller for related versus unrelated targets across sessions. N400 priming
      effects (amplitude differences between unrelated and related targets) were highly
      correlated across sessions (r=0.85, P<0.0001), but smaller in the second session
      due to larger N400s to related targets. CONCLUSIONS: N400 priming effects have
      high reliability over a one-week interval. They may decrease with repeat testing,
      possibly because of motivational changes. SIGNIFICANCE: Use of N400 priming
      effects in treatment studies should account for possible magnitude decreases with
      repeat testing. Further research is needed to delineate N400 priming effects'
      test-retest reliability and stability in different age and clinical groups, and
      with different stimulus types.

PMID- 23122709
TI  - Homogeneous sonophotolysis of food processing industry wastewater: Study of
      synergistic effects, mineralization and toxicity removal.
AB  - The mineralization of industrial wastewater coming from food industry using an
      emerging homogeneous sonophotolytic oxidation process was evaluated as an
      alternative to or a rapid pretreatment step for conventional anaerobic digestion
      with the aim of considerably reducing the total treatment time. At the selected
      operation conditions ([H(2)O(2)]=11,750ppm, pH=8, amplitude=50%, pulse length
      (cycles)=1), 60% of TOC is removed after 60min and 98% after 180min when treating
      an industrial effluent with 2114ppm of total organic carbon (TOC). This process
      removed completely the toxicity generated during storing or due to intermediate
      compounds. An important synergistic effect between sonolysis and photolysis
      (H(2)O(2)/UV) was observed. Thus the sonophotolysis (ultrasound/H(2)O(2)/UV)
      technique significantly increases TOC removal when compared with each individual
      process. Finally, a preliminary economical analysis confirms that the sono
      photolysis with H(2)O(2) and pretreated water is a profitable system when
      compared with the same process without using ultrasound waves and with no
      pretreatment.

PMID- 23122710
TI  - Early prognostic markers for fatal fulminant hepatic failure cases with viral
      hepatitis: proton nuclear magnetic resonance spectroscopic studies of serum.
AB  - BACKGROUND: Fulminant hepatic failure is associated with liver metabolic
      derangements which could have fatal consequences. The aim of the present study is
      to identify serum markers for early prediction of the outcome. METHODS: Proton
      nuclear magnetic resonance spectroscopic studies of serum of fulminant hepatic
      failure patients due to viral hepatitis with grade II/III of encephalopathy
      (twenty-four: ten prospective and fourteen retrospective) and twenty-five
      controls were undertaken. Of the twenty-four patients, fifteen survived with
      medical management alone while nine had fatal outcome. RESULTS: The results
      demonstrated significantly elevated indices of amino acids (alanine, lysine,
      glutamine, histidine, tyrosine, phenylalanine and 1,2-propanediol) in fatal cases
      compared to survivors and controls. Principal component analysis showed clear
      separation of fatal and surviving cases. Liver function parameters were
      significantly deranged in patients but they failed to provide early significant
      differences between surviving and fatal cases. Compared to model for end-stage
      liver disease scores, principal component analysis appear to be better as an
      early prognostic indicator. Biochemical mapping of pathways suggested
      interruptions in amino acid metabolism and urea cycle. CONCLUSIONS: Proton
      nuclear magnetic resonance studies of serum have the potential of rapidly
      identifying patients with irreversible fulminant hepatic failure requiring liver
      transplantation as life saving option.

PMID- 23122711
TI  - Is troponin T a useful marker of myocardial damage in acute pancreatitis? A
      prospective time course study.

PMID- 23122712
TI  - Characterization of fracture toughness exhaustion in pig aorta.
AB  - BACKGROUND: Spontaneous rupture of the aorta (SRA) without aneurysm, dissection,
      inflammation or infection of the aortic wall can be of two types: traumatic and
      non-traumatic. SRA is most of the time a fatal event. Consequently, it is
      important to understand the conditions which lead to the aortic rupture, and, in
      the case of non-traumatic SRA, to predict the temporal likelihood of rupture.
      METHOD OF APPROACH: The present work incorporates the temporal aspect by
      examining the effects of fatigue on aortic wall properties, and adopts an energy
      approach, based on fracture toughness, to evaluate the aorta's resistance to
      rupture. Fracture toughness characterization is a destructive testing process and
      as a consequence cannot be implemented as a clinical tool. However, using
      concepts in damage mechanics, in theory, it should be possible to indirectly
      assess fracture toughness from other mechanical properties, such as aortic wall
      stiffness. Tissue samples from non-aneurysmal porcine aortas were fatigued and
      were subjected to both biaxial and guillotine tests to assess wall stiffness
      variations and fracture toughness exhaustion, respectively. RESULTS: The
      experiments reveal that aortic wall stiffness variations and fracture toughness
      exhaustion decreased as a function of loading cycles and can be modeled with
      exponential functions. After one million loading cycles, the stiffness ratio
      between the non-fatigued sample and the fatigued sample, dropped to about 0.85,
      while the fracture toughness ratio counterpart fell to about 0.80. CONCLUSION:
      Consequently, the changes in both stiffness and fracture toughness as a function
      of applied fatigue cycles can be measured in aortic tissues. Moreover, these
      results suggest the possibility to use fracture toughness exhaustion curves as a
      fatigue criterion.

PMID- 23122713
TI  - Bond strength of a dental leucite-based glass ceramic to a resin cement using
      different silane coupling agents.
AB  - AIM: To evaluate the effect of different types of novel silane coupling agents
      with two concentrations on the micro-tensile bond strength of a dental glass
      ceramic with leucite crystals to a dual-cured resin cement using an optimized
      method of silane application. METHODS: Leucite-reinforced feldspathic ceramic
      blocks were fabricated, wet ground and cleansed. The bonding ceramic surfaces
      were treated with different organosilane solutions as follows: Control silane:
      Monobond S; methacryloxypropyltrimethoxy silane and experimental silanes with two
      concentrations (1.0 and 2.5 vol%): amino, isocyanate, styryl, and acrylate
      silanes. The silane application method consisted of brush application, hot air
      drying followed by rinsing with hot water and drying. Then a thin layer of an
      unfilled resin and a dual-cured resin cement was light-cured on the ceramic
      surfaces. The resin-ceramic blocks were stored in distilled water at 37 degrees C
      for 24 h and sectioned to produce beam specimens (n=17) with a 1.0 mm(2) cross
      sectional area. Specimens were then subjected to thermocycling and tested in a
      micro-tensile tester device. Data were analyzed using analysis of variance and
      Tamhane post-hoc test. RESULTS: The mean micro-tensile bond strength value for
      the styryl silane was significantly higher (P<0.05) than the other types of
      silanes except for the Monobond S. The mean bond strength values for isocyanate
      silanes were significantly lower than the other silanes tested (P<0.05). No
      statistically significant difference in the bond strength between the 1.0 and 2.5
      vol% of experimental silanes was observed (P>0.05). CONCLUSIONS: The micro
      tensile bond strength of the leucite-based dental glass ceramic to a resin cement
      was affected by the type of silane coupling agent and not by the concentration of
      silane solutions. The best bond strength overall was achieved by
      methacryloxypropyltrimethoxysilane and experimental styryl silane solutions.

PMID- 23122714
TI  - Substrate elasticity controls cell proliferation, surface marker expression and
      motile phenotype in amniotic fluid-derived stem cells.
AB  - The physical cues presented to stem cells by the substrate on or in which they
      exist have been shown to play a crucial role in regulation of their behavior.
      Until recently, most research has focused on the effects of substrate elasticity
      on differentiation capability rather than maintenance of long-term proliferation
      and plasticity. The main goal of the present study is to study the interaction of
      amniotic fluid-derived stem (AFS) cells with growth substrata of different
      elasticity, which may extend their application potentials. Here, we investigate
      the effects of elastic modulus (E'), on AFS cell proliferation, morphology, cell
      surface marker expression, and autocrine stimulation of cell migration. AFS cells
      cultured on substrates of different E' exhibited significant changes in
      proliferation and morphology. Immunohistochemistry revealed increased expression
      of cell surface markers associated with mesenchymal stem cells (MSCs) (CD44,
      CD90, CD105, and N-cadherin) in cells cultured on softer substrates.
      Additionally, AFS cells cultured on softer substrates induced autocrine
      stimulation of migration. Therefore, tailoring the elastic modulus of
      biomaterials to specific stiffness values is an effective method to control stem
      cell properties, which may modulate the effectiveness of their therapeutic
      applications.

PMID- 23122715
TI  - Bioresorbable screws reinforced with phosphate glass fibre: manufacturing and
      mechanical property characterisation.
AB  - Use of bioresorbable screws could eliminate disadvantages associated with metals
      such as removal operations, corrosion, MRI interference and stress shielding.
      Mechanical properties of bioresorbable polymers alone are insufficient for load
      bearing applications application as screws. Thus, reinforcement is necessary to
      try and match or surpass the mechanical properties of cortical bone. Phosphate
      based glass fibres were used to reinforce polylactic acid (PLA) in order to
      produce unidirectionally aligned (UD) and unidirectionally plus randomly
      distributed (UD/RM) composite screws (P40 UD and P40 UD/RM). The maximum flexural
      and push-out properties for the composite screws (P40 UD and P40 UD/RM) increased
      by almost 100% in comparison with the PLA screws. While the pull-out strength and
      stiffness of the headless composite screws were ~80% (strength) and ~130%
      (stiffness) higher than for PLA, those with heads exhibited properties lower than
      those for PLA alone as a result of failure at the heads. An increase in the
      maximum shear load and stiffness for the composite screws (~30% and ~40%) in
      comparison to the PLA screws was also seen. Maximum torque for the PLA screws was
      ~1000 mN m, while that for the composite screws were slightly lower. The SEM
      micrographs for P40 UD and P40 UD/RM screws revealed small gaps around the
      fibres, which were suggested to be due to buckling of the UD fibres during the
      manufacturing process.

PMID- 23122716
TI  - Investigation of microstructure, mechanical properties and cellular viability of
      poly(L-lactic acid) tissue engineering scaffolds prepared by different thermally
      induced phase separation protocols.
AB  - Two thermally induced phase separation (TIPS) methods have been used to fabricate
      biodegradable poly(L-lactic acid) (PLLA) tissue engineering scaffolds each with
      fibrous (F-TIPS) and porous (P-TIPS) microstructures. Three levels of PLLA
      concentration (3, 5 and 7 wt%) were employed in each fabrication method and both
      wet and dry specimens were studied. Simple compression testing revealed that an
      elastic-plastic representation of the mechanical behavior was possible for all
      specimens. Both elastic and plastic moduli were higher for the P-TIPS, for higher
      polymer concentration, and might be somewhat higher for dry as opposed to wet
      specimens. For F-TIPS specimens, permanent deformation occurred successively
      during cyclic deformation but a "memory effect" simplified the behavior. Although
      F-TIPS microstructure better resembled the natural extracellular matrix, human
      osteosarcoma fibroblast cells showed more consistent viability in the P-TIPS
      scaffolds under our unloaded test protocols. Biodegradation in cell culture
      medium resulted in a decreased elastic moduli for F-TIPS specimens. Information
      presented regarding the microstructure, mechanical properties and cell viability
      of these PLLA scaffolds that should help reduce the number of iterations involved
      in developing tissue engineering products.

PMID- 23122717
TI  - Characterization of controlled highly porous hyaluronan/gelatin cross-linking
      sponges for tissue engineering.
AB  - This study examines the suitability of N-(3-dimethylaminopropyl)-N'
      ethylcarbodiimide hydrochloride for use as a cross-linker in the preparation of
      highly porous hyaluronan (HA)/gelatin sponges through the solvent casting and
      particulate leaching (SCPL) process. The modulus, water absorption rate, bonding,
      morphology, cell viability, and chondrocyte mRNA expression of the HA/gelatin
      sponges were measured and compared. Water uptake by the sponges resulted in pores
      with spherical diameters ranging from 100MUm to 200MUm. With higher porosity, the
      strength and modulus declined. Larger salt leaching amounts resulted in higher
      water uptake. The cross-linking bonds in the HA/gelatin sponges were mostly ester
      bonds. According to our study, the amount of salt in the SCPL process was the
      main factor that influenced strength, pore interconnectivity, and water uptake
      ability. The results also showed that the scaffold had a non-viability effect on
      human chondrocytes, but the mRNA expression level of aggrecan and type II
      collagen in the cartilage was significantly higher than that of the control group
      after 5d of culture. The sponges developed in the present study are potential
      candidates for chondrocyte proliferation and differentiation in cartilage
      regeneration.

PMID- 23122718
TI  - Chromium picolinate attenuates hyperglycemia-induced oxidative stress in
      streptozotocin-induced diabetic rats.
AB  - Chromium picolinate is advocated as an anti-diabetic agent for impaired glycemic
      control. It is a transition metal that exists in various oxidation states and may
      thereby act as a pro-oxidant. The present study has been designed to examine the
      effect of chromium picolinate supplementation on hyperglycemia-induced oxidative
      stress. Diabetes was induced in male Wistar rats by a single intraperitoneal
      injection of streptozotocin (50mg/kg body weight) and chromium was administered
      orally as chromium picolinate (1mg/kg body weight) daily for a period of four
      weeks after the induction of diabetes. As is characteristic of diabetic
      condition, hyperglycemia was associated with an increase in oxidative stress in
      liver in terms of increased lipid peroxidation and decreased glutathione levels.
      The activity of antioxidant enzymes like superoxide dismutase, catalase and
      glutathione reductase were significantly reduced in liver of diabetic animals.
      Levels of alpha-tocopherol and ascorbic acid were found to be considerably lower
      in plasma of diabetic rats. Chromium picolinate administration on the other hand
      was found to have beneficial effect in normalizing glucose levels, lipid
      peroxidation and antioxidant status. The results from the present study
      demonstrate potential of chromium picolinate to attenuate hyperglycemia-induced
      oxidative stress in experimental diabetes.

PMID- 23122719
TI  - Classifying depression patients and normal subjects using machine learning
      techniques and nonlinear features from EEG signal.
AB  - Diagnosing depression in the early curable stages is very important and may even
      save the life of a patient. In this paper, we study nonlinear analysis of EEG
      signal for discriminating depression patients and normal controls. Forty-five
      unmedicated depressed patients and 45 normal subjects were participated in this
      study. Power of four EEG bands and four nonlinear features including detrended
      fluctuation analysis (DFA), higuchi fractal, correlation dimension and lyapunov
      exponent were extracted from EEG signal. For discriminating the two groups, k
      nearest neighbor, linear discriminant analysis and logistic regression as the
      classifiers are then used. Highest classification accuracy of 83.3% is obtained
      by correlation dimension and LR classifier among other nonlinear features. For
      further improvement, all nonlinear features are combined and applied to
      classifiers. A classification accuracy of 90% is achieved by all nonlinear
      features and LR classifier. In all experiments, genetic algorithm is employed to
      select the most important features. The proposed technique is compared and
      contrasted with the other reported methods and it is demonstrated that by
      combining nonlinear features, the performance is enhanced. This study shows that
      nonlinear analysis of EEG can be a useful method for discriminating depressed
      patients and normal subjects. It is suggested that this analysis may be a
      complementary tool to help psychiatrists for diagnosing depressed patients.

PMID- 23122720
TI  - Understanding symptomatology of atherosclerotic plaque by image-based tissue
      characterization.
AB  - Characterization of carotid atherosclerosis and classification into either
      symptomatic or asymptomatic is crucial in terms of diagnosis and treatment
      planning for a range of cardiovascular diseases. This paper presents a computer
      aided diagnosis (CAD) system (Atheromatic) that analyzes ultrasound images and
      classifies them into symptomatic and asymptomatic. The classification result is
      based on a combination of discrete wavelet transform, higher order spectra (HOS)
      and textural features. In this study, we compare support vector machine (SVM)
      classifiers with different kernels. The classifier with a radial basis function
      (RBF) kernel achieved an average accuracy of 91.7% as well as a sensitivity of
      97%, and specificity of 80%. Thus, it is evident that the selected features and
      the classifier combination can efficiently categorize plaques into symptomatic
      and asymptomatic classes. Moreover, a novel symptomatic asymptomatic carotid
      index (SACI), which is an integrated index that is based on the significant
      features, has been proposed in this work. Each analyzed ultrasound image yields
      on SACI number. A high SACI value indicates that the image shows symptomatic and
      low value indicates asymptomatic plaques. We hope this SACI can support vascular
      surgeons during routine screening for asymptomatic plaques.

PMID- 23122721
TI  - Trends in the incidence of stroke and cardiovascular risk factors on the isolated
      island of Okinawa: the Miyakojima study.
AB  - BACKGROUND: Rapid deterioration of cardiovascular risk control, especially
      obesity, has occurred in Okinawa; this may affect cardiovascular disease
      incidence, including stroke. METHODS: Cross-sectional field studies were
      conducted in 2 periods, 1988-1991 as the first period, and 2002-2005 as the
      second period, in the isolated island of Okinawa, Miyakojima. To evaluate
      population backgrounds related to cardiovascular risk factors, data from the
      health checkup programs conducted in 1987 and 2001 were surveyed. RESULTS: Total
      of 257 patients in the first period and 370 in the second were diagnosed with
      first-time stroke. The age-adjusted annual incidence rate of first-time stroke of
      the first and second periods was 124 and 144 per 100,000 standard population of
      Japan. The age-adjusted annual incidence rate showed an upward trend for brain
      infarction (50 to 73) and downward trend for brain hemorrhage (61 to 54);
      however, those trends were not significant. The health checkup surveys
      illustrated that blood pressure decreased in all age groups during the second
      survey period. However, the body mass index increased in patients aged 50 years
      or more. Fasting blood glucose levels of patients aged 30-79 years and non-HDL
      cholesterol levels of patients aged 50-79 years significantly increased.
      CONCLUSIONS: In Miyakojima, the incidence of first-time stroke and all of its
      subtypes did not change significantly between two periods, even though blood
      pressure decreased significantly in the second period. Metabolic deterioration
      may be associated with the upward trend in incidence of brain infarction.

PMID- 23122722
TI  - The totaled health risks in vascular events (THRIVE) score predicts ischemic
      stroke outcomes independent of thrombolytic therapy in the NINDS tPA trial.
AB  - BACKGROUND: To date, no ischemic stroke outcome prediction scores have been
      validated for use in the setting of both endovascular and non-endovascular stroke
      treatments. The Totaled Health Risks in Vascular Events (THRIVE) score has been
      previously validated in patients undergoing endovascular stroke treatment, and we
      hypothesized that it would perform similarly well in patients receiving
      intravenous tissue plasminogen activator (tPA) or no acute therapy. METHODS: We
      compared the performance of the THRIVE score between patients in the National
      Institutes of Neurological Disorders and Stroke (NINDS) tPA trial and patients in
      the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) trials of
      endovascular stroke treatment. The predictive performance of the THRIVE score was
      compared using receiver operator characteristic (ROC) curve analysis. In the
      NINDS cohort, separate analyses were also performed for patients receiving tPA
      versus those receiving placebo. RESULTS: ROC curve analysis revealed a good
      prediction of outcomes across the range of THRIVE scores in both the NINDS and
      MERCI datasets. As we have previously found in the MERCI datasets, the THRIVE
      score, which encompasses the National Institutes of Health Stroke Scale (NIHSS)
      score, age, and chronic disease burden, was a better predictor of outcomes than
      NIHSS and age alone in the NINDS trial dataset. THRIVE score and tPA
      administration both strongly predicted outcome, but these effects were
      statistically independent. CONCLUSIONS: The THRIVE score provides accurate
      prediction of long-term neurologic outcomes in patients with acute ischemic
      stroke regardless of treatment modality. Both the THRIVE score and tPA
      administration predict outcome, but the THRIVE score does not influence the
      impact of tPA on outcome, and tPA administration does not influence the impact of
      THRIVE score on outcome.

PMID- 23122723
TI  - Impaired renal function is not associated with increased volume of intracerebral
      hemorrhage.
AB  - BACKGROUND: Patients with low glomerular filtration rate (GFR) are at risk for
      hemorrhagic stroke and experience poor long-term outcomes after stroke. These
      associations may be mediated by hematoma volume. We investigated the relationship
      between impaired renal function (GFR <60 mL/min/1.73 m(2)) and hematoma size.
      METHODS: Consecutive patients admitted with spontaneous intracerebral hemorrhage
      (sICH) between August 2006 and January 2010 were evaluated; patients with acute
      kidney injury or end stage renal disease were excluded. Data on patient
      demographics, admission creatinine, size and location of bleed, and disposition
      at discharge were collected. Hematoma size and location and discharge outcomes
      were compared among those with normal and impaired renal function. RESULTS: Among
      573 patients admitted with sICH, 411 met our study criteria (mean age 61.4 years;
      52.3% female; median ICH volume 11.2 mL). Mean GFR was 73.8 mL/min/1.73 m(2), and
      99 patients (24.1%) had a GFR <60 mL/min/1.73 m(2). There was no correlation
      between admission GFR and ICH volume (rs = 0.014; P = .77); those with GFR <60
      versus >=60 mL/min/1.73 m(2) also had similar ICH volumes (median 10.8 v 11.4 mL;
      P = .54). There was no association between in-hospital mortality and admission
      GFR, although those with GFR <60 mL/min/1.73 m(2) were more likely to die or be
      discharged to nursing homes (adjusted odds ratio 1.9; P = .03). CONCLUSIONS: In a
      large sICH cohort, impaired renal function was not associated with final hematoma
      volume. Additional study should focus on the mechanism by which renal function
      impacts functional outcomes after sICH.

PMID- 23122724
TI  - Differences in pregnancy planning between women aged 18-44, with and without
      diabetes: behavioral risk factor surveillance system analysis.
AB  - AIM: Assess differences in pregnancy planning and behavioral risk factors among
      women of reproductive age, by diabetes status. METHODS: A secondary analysis of
      cross-sectional data from the Behavioral Risk Factor Surveillance System (2002
      and 2004) was conducted. Subjects were 18-44-year-old, non-pregnant, fertile
      women, grouped into two categories: non-diabetes (n=57,436), and diabetes
      (n=2929). Multivariable logistic regression was used to estimate adjusted
      prevalence odds ratios and 95% confidence intervals. RESULTS: Approximately 93%
      of women of reproductive age with or without diabetes are not intending a
      pregnancy, and yet among them, women with diabetes are 22% more likely not to use
      any birth control at all. Women with diabetes are 3.4 times more likely to be
      obese, 1.4 times more likely to be overweight, 35% less likely to drink any
      alcohol, and 27% less likely to binge drink alcohol, than women without diabetes.
      There were no differences in risk factors between women with diabetes that were
      and were not intending a pregnancy. CONCLUSIONS: Birth control nonuse for women
      with diabetes not intending a pregnancy and lack of behavioral change for women
      with diabetes intending a pregnancy, combined with an increasing prevalence in
      diabetes, will likely result in significant economic and social tolls on society.

PMID- 23122725
TI  - Evidence-based dentistry and the need for clinically relevant models to predict
      material performance.

PMID- 23122726
TI  - Short-term treatment with metformin suppresses toll like receptors (TLRs)
      activity in isoproterenol-induced myocardial infarction in rat: are AMPK and TLRs
      connected?
AB  - AMP-activated protein kinase (AMPK) is a key sensor of cellular energy. The
      activation of AMPK by metformin prevents cardiac remodeling after myocardial
      infarction (MI). Besides, the innate immune response through TLRs is activated
      during MI. In the present study, the effects of short-term treatment with
      metformin on TLRs activity and its relation with AMPK in isoproterenol-induced MI
      were assessed in rats. To induce MI, a subcutaneous injection of isoproterenol
      was given to Wistar rats for two consecutive days. Metformin (25, 50, and
      100mg/kg) was orally administered to rats twice daily for two days. Interstitial
      fibrosis was dose-dependently attenuated in the treated groups in comparison to
      the MI group (score: 1.25 +/- 0.28 with 100 mg/kg metformin versus 3.5 +/- 0.28;
      P<0.001). Further, metformin reduced TLR-dependent inflammatory cytokines as
      indexed by reduced myocardial levels of TNFalpha (maximum 68%; P<0.001) and IL6
      (maximum 84%; P<0.001) as well as by reduced myocardial MPO activity (25%;
      P<0.01). It was found that the level of phosphorylated AMPK was significantly
      upregulated by 165% (P<0.001) when treated with 100 mg/kg of metformin, but not
      with 25 and 50mg/kg. This was associated with a remarkable suppression of TLR4
      expression and reduction of protein level of TLRs adapter protein, MyD88 (P<0.01)
      in the infarcted myocardium. These results suggest that AMPK activation by
      metformin and the subsequent suppression of TLRs activity could be considered as
      a target in protecting the infarcted heart, which may indicate a link between
      AMPK and TLRs.

PMID- 23122727
TI  - Anti-inflammatory properties of rose oxide.
AB  - Rose-oxide is a fragrance found in roses and rose oil. There are no reports about
      the pharmacological activity of this molecule. The present study was undertaken
      to evaluate whether rose-oxide (RO) has anti-inflammatory properties and to
      investigate possible mechanisms involved with its effects. The anti-inflammatory
      activity of RO was first suggested by the formalin test in mice, an inflammatory
      pain model, because intraperitoneal (i.p.) administration of RO (50 and 100mg/kg)
      inhibited only the late phase of this test. To further investigate the anti
      inflammatory properties of RO, the complete Freund's adjuvant (CFA)- and
      carrageenan-induced paw inflammation models were used. Pre-treatment with RO (50
      and 100mg/kg) significantly reduced paw edema at 4, 6 and 24h after the CFA
      injection. In addition, RO (100mg/kg) reduced the IL-1beta, but not TNF-alpha,
      local production induced by CFA. Administration of RO (25-100mg/kg) decreased the
      paw edema induced by carrageenan in rats, which was more evident at 3 and 4h
      after induction. In addition, neutrophil migration to the hind paw was measured
      by MPO assay after the carrageenan injection. The MPO activity was significantly
      inhibited by RO at 25-100mg/kg, 4h after stimulus. In another experimental set,
      administration of RO (25-100mg/kg) significantly reduced the leukocyte migration
      in the carrageenan-induced peritonitis model in mice. The results described here
      are the first report of pharmacological properties of RO and strongly suggest
      that RO possesses anti-inflammatory activity related to its ability to inhibit
      the IL-1beta production and the leukocyte migration.

PMID- 23122729
TI  - Use of sorbents for purification of lead, copper and antimony in runoff water
      from small arms shooting ranges.
AB  - Different sorbents were tested in situ for their ability to reduce the
      concentration of Cu, Sb and Pb in drainage water from a shooting range. The
      sorbents tested were: Brimac((r)) charcoal, olivine mixed with elemental iron
      powder, magnetite and Kemira((r)) iron hydroxide. The mean sorption of Cu, Sb and
      Pb was 84%, 66%, 85% with Brimac((r)) charcoal and 58%, 78% and 69% with
      Kemira((r)) iron hydroxide. Good sorption of Cu and Pb was achieved using olivine
      with 5% elemental Fe powder, which resulted in a sorption of 81% and 87%,
      respectively. The Fe-olivine filters were less efficient in reducing the
      concentration of Sb, but increasing the Fe content improved Sb sorption. In
      periods with high concentrations of Pb, Cu and Sb in the creek, such as during
      precipitation, the sorbent efficacy improved. This might be due to changes in the
      physico-chemical form of the metals, or to a higher fraction of elements being
      physically retained in the form of particles or colloids.

PMID- 23122728
TI  - Caspase 3 cleavage of the inositol 1,4,5-trisphosphate receptor does not
      contribute to apoptotic calcium release.
AB  - An important role in the regulation of apoptotic calcium release is played by the
      ubiquitously expressed family of inositol 1,4,5-trisphosphate receptor (IP(3)R)
      channels. One model for IP(3)R activation during apoptosis is cleavage by the
      apoptotic protease caspase 3. Here we show that early elevations in cytosolic
      calcium during apoptosis do not require caspase 3 activity. We detected a robust
      increase in calcium levels in response to staurosporine treatment in primary
      human fibroblasts and HeLa cells in the presence of the caspase inhibitor Z-VAD,
      indicating that calcium release during the initiation of apoptosis occurs
      independently of caspase 3. Similar results were obtained with MCF-7 cells which
      lack caspase 3 expression. Stable expression of caspase 3 in MCF-7 cells and TAT
      based transduction of the active recombinant caspase 3 directly into living MCF-7
      cells had marginal effects on the early events leading to cytosolic calcium
      elevations and irreversible commitment to apoptotic cell death. Significantly,
      blocking IP(3) binding to the IP(3)R with an IP(3) sponge resulted in suppression
      of staurosporine-induced calcium release and cell death. Collectively, our
      results suggest that generation of IP(3) is sufficient for the initiation of
      apoptotic calcium signaling, and caspase 3-mediated truncation of IP(3)R channel
      is a consequence, not causative, of apoptotic calcium release.

PMID- 23122730
TI  - Adsorptional photocatalytic degradation of methylene blue onto pectin-CuS
      nanocomposite under solar light.
AB  - This study describes the effect of adsorption on methylene blue degradation using
      pectin-CuS nanocomposite (PCSNC). The nanocomposite was synthesized using co
      precipitation methods followed by direct encapsulation with pectin. The
      synthesized nanocomposite was characterized by SEM, TEM, XRD, FTIR and UV-vis
      spectral technique. The adsorption and photocatalytic efficiencies of PCSNC were
      compared with copper sulphide nanoparticle (CSNP). The dye removal was studied
      under different reaction conditions. The adsorption capacity of pectin based
      nanocomposite was higher due to other free functional group on pectin surface
      after connecting to nanoparticles. The simultaneous adsorption and
      photodegradation process (A+P) was the most efficient process due to rapid
      destruction of adsorbed dye molecules. The complete COD removal was attained in
      10h using PCSNC/A+P process. On comparing with CSNP, pectin-CuS nano composite
      showed more degradation efficiency and reusability for MB degradation.

PMID- 23122731
TI  - Toxicity of benz(a)anthracene and fluoranthene to marine phytoplankton in
      culture: does cell size really matter?
AB  - The toxicity of benz(a)anthracene and fluoranthene (polycyclic aromatic
      hydrocarbons, PAHs) was evaluated on seven species of marine algae in culture
      belonging to pico-, nano-, and microphytoplankton, exposed to increasing
      concentrations of up to 2 mg L(-1). The short-term (24h) toxicity was assessed
      using chlorophyll a fluorescence transients, linked to photosynthetic parameters.
      The maximum quantum yield Fv/Fm was lower at the highest concentrations tested
      and the toxicity thresholds were species-dependent. For acute effects,
      fluoranthene was more toxic than benz(a)anthracene, with LOECs of 50.6 and 186
      MUg L(-1), respectively. After 72 h exposure, there was a dose-dependent decrease
      in cell density, fluoranthene being more toxic than benz(a)anthracene. The
      population endpoint at 72 h was affected to a greater extent than the
      photosynthetic endpoint at 24h. EC50 was evaluated using the Hill model, and
      species sensitivity was negatively correlated to cell biovolume. The largest
      species tested, the dinoflagellate Alexandrium catenella, was almost insensitive
      to either PAH. The population endpoint EC50s for fluoranthene varied from 54 MUg
      L(-1) for the picophytoplankton Picochlorum sp. to 418 MUg L(-1) for the larger
      diatom Chaetoceros muelleri. The size/sensitivity relationship is proposed as a
      useful model when there is a lack of ecotoxicological data on hazardous
      chemicals, especially in marine microorganisms.

PMID- 23122732
TI  - Efficient removal of dyes by a novel magnetic Fe3O4/ZnCr-layered double hydroxide
      adsorbent from heavy metal wastewater.
AB  - A novel magnetic Fe(3)O(4)/ZnCr-layered double hydroxide adsorbent was produced
      from electroplating wastewater and pickling waste liquor via a two-step microwave
      hydrothermal method. Adsorption of methyl orange (MO) from water was studied
      using this material. The effects of three variables have been investigated by a
      single-factor method. The response surface methodology (RSM) based on Box-Behnken
      design was successfully applied to the optimization of the preparation
      conditions. The maximum adsorption capacity of MO was found to be 240.16 mg/g,
      indicating that this material may be an effective adsorbent. It was shown that
      99% of heavy metal ions (Fe(2+), Fe(3+), Cr(3+), and Zn(2+)) can be effectively
      removed into precipitates and released far less in the adsorption process. In
      addition, this material with adsorbed dye can be easily separated by a magnetic
      field and recycled after catalytic regeneration with advanced oxidation
      technology. Meanwhile, kinetic models, FTIR spectra and X-ray diffraction pattern
      were applied to the experimental data to examine uptake mechanism. The boundary
      layer and intra-particle diffusion played important roles in the adsorption
      mechanisms.

PMID- 23122733
TI  - Use of metakaolin to stabilize sewage sludge ash and municipal solid waste
      incineration fly ash in cement-based materials.
AB  - The landfilling of municipal incineration residues is an expensive option for
      municipalities. This work evaluates an alternative way to render waste inert in
      cement-based materials by combining the reduction of waste content with the
      immobilization properties of metakaolin (MK). The functional and environmental
      properties of ternary and quaternary binders using cement, metakaolin, and two
      industrial by-products from combustion processes (MSWIFA - Municipal Solid Waste
      Incineration Fly Ash and SSA - Sewage Sludge Ash) were evaluated. The binders
      were composed of 75% cement, 22.5% metakaolin and 2.5% residue. Results on the
      impact of residues on the functional and environmental behavior of mortars showed
      that the mechanical, dimensional and leaching properties were not affected by the
      residues. In particular, the use of metakaolin led to a significant decrease in
      soluble fractions and heavy metals released from the binder matrix. The results
      are discussed in terms of classification of the leaching behavior, efficiency and
      role of metakaolin in the immobilization of heavy metals in of MSWIFA and SSA,
      and the pertinence of the dilution process.

PMID- 23122734
TI  - Application of natural citric acid sources and their role on arsenic removal from
      drinking water: a green chemistry approach.
AB  - Solar Oxidation and Removal of Arsenic (SORAS) is a low-cost non-hazardous
      technique for the removal of arsenic (As) from groundwater. In this study, we
      tested the efficiency of natural citric acid sources extracted from tomato, lemon
      and lime to promote SORAS for As removal at the household level. The experiment
      was conducted in the laboratory using both synthetic solutions and natural
      groundwater samples collected from As-polluted areas in West Bengal. The role of
      As/Fe molar ratios and citrate doses on As removal efficiency were checked in
      synthetic samples. The results demonstrate that tomato juice (as citric acid) was
      more efficient to remove As from both synthetic (percentage of removal: 78-98%)
      and natural groundwater (90-97%) samples compared to lemon (61-83% and 79-85%,
      respectively) and lime (39-69% and 63-70%, respectively) juices. The As/Fe molar
      ratio and the citrate dose showed an 'optimized central tendency' on As removal.
      Anti-oxidants, e.g. 'hydroxycinnamates', found in tomato, were shown to have a
      higher capacity to catalyze SORAS photochemical reactions compared to
      'flavanones' found in lemon or lime. The application of this method has several
      advantages, such as eco- and user- friendliness and affordability at the
      household level compared to other low-cost techniques. 

PMID- 23122735
TI  - A mandibular advancement device for the treatment of obstructive sleep apnea:
      long-term use and tolerance.
AB  - Long-term efficacy and compliance with mandibular advancement devices (MAD) in
      the treatment of obstructive sleep apnea syndrome (OSAS) are under-studied. Our
      objective was to conduct a long-term assessment of the OPM4J device, measuring
      symptoms, compliance rate, and adverse effects in a cohort of consecutive
      patients treated with OPM4J for an average period of nearly three years. Out of
      140 patients aged 62 +/- 10 years with body mass index (BMI) 27 +/- 4 kg/m(2) and
      initial apnea-hypopnea index (AHI) 27 +/- 16, complete reversal of OSAS was
      achieved in 65%. A total of 76% reported regular MAD use, with 24% stopping
      treatment and half of those 24% falling back on continuous positive airway
      pressure (CPAP). Patients with lower residual AHI or residual Epworth scores at
      month 3 were more likely to continue treatment (P < 0.007 and P < 0.02). Reasons
      for discontinuing treatment included tooth pain, persistent snoring or fatigue,
      loss or breakage of the device, and the cost of replacing it. OPM4J reduced OSAS
      symptoms in the long-term. Regular use was reported in 76% of patients. Adverse
      effects were common but minor. Half of non-users were lost to follow-up and
      probably remain without treatment.

PMID- 23122737
TI  - Assessment of skeletal maturation based on cervical vertebrae in CBCT.
AB  - Diagnosis of skeletal age in adolescents helps orthodontists select and time
      treatments. Currently this is done using lateral cephalometric radiographs. This
      study evaluates the application of the conventional method in cone-beam computer
      tomographic (CBCT) images to bring forth assessment of skeletal maturation in
      three-dimensions. Ninety-eight lateral cephalometric radiographs and CBCT scans
      were collected from orthodontic patients between 11 to 17 years of age over an 18
      month period. CBCT scans were examined in seven sagittal slices based on cervical
      vertebral maturation staging (CVMS). Collected CVMS values were compared with
      those from corresponding lateral cephalometric radiograph. CVMS measured from
      CBCT and lateral cephalometric radiographs were the same on average. However,
      they were not consistent with each other and scored interclass correlation
      coefficient of 0.155 in validity test. Interoperator reliability was weak
      (0.581). Adaptation of cervical vertebrae maturation staging in CBCT requires
      further clarifications or modifications to become consistent with lateral
      cephalometric examinations and to become a reliable method. Alternatively, a
      completely new method may be developed consisting of maturational indicators or
      landmarks unique to CBCT imaging.

PMID- 23122740
TI  - Emotion recognition in psychosis: no evidence for an association with real world
      social functioning.
AB  - BACKGROUND: Patients with psychotic disorders show impairments in the recognition
      of emotions in other people. These impairments have been associated with poor
      social functioning as measured by self-report questionnaires, clinical interviews
      and laboratory-based tests of social skills. The ecological validity of these
      tests, however, is low. Associations were examined between emotion recognition
      and daily life social interactions in 50 patients diagnosed with a non-affective
      psychotic disorder and 67 healthy controls. METHODS: All participants were
      assessed with the Degraded Facial Affect Recognition Task (DFAR), a computer test
      measuring the recognition of emotional facial expressions. Social functioning in
      daily life was assessed using the Experience Sampling Method (a random time
      sampling technique) with focus on measures of social context and appraisal of the
      social situation. RESULTS: Groups differed significantly in the recognition of
      angry faces, whereas no differences existed for other emotions. There were no
      associations between emotion recognition and social functioning in daily life and
      there was no evidence for differential associations in patients as compared to
      controls. DISCUSSION: Social functioning, when assessed in an ecologically valid
      fashion, is not sensitive to variation in the traditional experimental assessment
      of emotion recognition. Real life measures of functioning should guide research
      linking the handicaps associated with psychosis to underlying cognitive and
      emotional dysregulation.

PMID- 23122742
TI  - Totally thoracoscopic surgical treatment for atrial septal defect: mid-term
      follow-up results in 45 consecutive patients.
AB  - BACKGROUND: Totally thoracoscopic operation provides minimally invasive
      alternative for patients with atrial septal defect. In this study, we report the
      mid-term follow-up results of 45 patients with atrial septal defect who underwent
      totally thoracoscopic operation and discuss the feasibility and safety of this
      new technique. METHODS: From January 2010 to February 2012, 45 patients with
      atrial septal defect underwent totally thoracoscopic closure as an alternative to
      traditional median sternotomy surgery. The mean age of the patients was 33.2+/
      12.5 years (range 6.3-61.5 years), and mean weight was 55.7+/-11.1 kg (range 30.5
      80 kg). Based on echocardiography the mean size of the atrial septal defect was
      16.0+/-10.8mm (range 13-39 mm). RESULTS: All patients underwent totally
      thoracoscopic repair. Twenty-five patients with a pericardial patch and 20
      patients were sutured directly. Five patients underwent concomitant tricuspid
      valvuloplasty with Kay technique. No death, reoperation or complete
      atrioventricular block occurred. The mean time of cardiopulmonary bypass was
      70.5+/-20.6 min (range 31.0-153.0 min), the mean time of aortic cross-clamp was
      28.8+/-13.3 min (range 0.0-80.0 min) and the mean time of operation was 155.8+/
      36.8 min (range 65.0-300.0 min). Postoperative mechanical ventilation averaged
      5.1+/-2.8h (range 3.6-12.6h), and the duration of intensive care unit stay 20.0+/
      5.6h (range 16.2-25 h). The mean volume of blood drainage was 156+/-36 ml (range
      51-800 ml). No death, residual shunt, lung atelectasis or moderate tricuspid
      regurgitation was found at three-month follow-up. CONCLUSION: Totally
      thoracoscopic repair is feasible and safe for patients with ASD, even with or
      without tricuspid regurgitation however more clinical data is needed in the
      future study.

PMID- 23122741
TI  - Aerobic degradation of aromatic compounds.
AB  - Our view on the bacterial responses to the aerobic degradation of aromatic
      compounds has been enriched considerably by the current omic methodologies and
      systems biology approaches, revealing the participation of intricate metabolic
      and regulatory networks. New enzymes, transporters, and specific/global
      regulatory systems have been recently characterized, and reveal that the
      widespread biodegradation capabilities extend to unexpected substrates such as
      lignin. A completely different biochemical strategy based on the formation of
      aryl-CoA epoxide intermediates has been unraveled for aerobic hybrid pathways,
      such as those involved in benzoate and phenylacetate degradation. Aromatic
      degradation pathways are also an important source of metabolic exchange factors
      and, therefore, they play a previously unrecognized biological role in cell-to
      cell communication. Beyond the native bacterial biodegradation capabilities,
      pathway evolution as well as computational and synthetic biology approaches are
      emerging as powerful tools to design novel strain-specific pathways for
      degradation of xenobiotic compounds.

PMID- 23122739
TI  - Social cognition in 22q11.2 microdeletion syndrome: relevance to psychosis?
AB  - 22q11.2 deletion syndrome (22qDS) represents one of the largest known genetic
      risk factors for schizophrenia. Approximately 30% of individuals with 22qDS
      develop psychotic illness in adolescence or young adulthood. Given that deficits
      in social cognition are increasingly viewed as a central aspect of idiopathic
      schizophrenia, we sought to investigate abilities in this domain as a predictor
      of psychotic symptoms in 22qDS participants. We assessed multiple domains of
      social and non-social cognition in 22qDS youth to: 1) characterize performance
      across these domains in 22qDS, and identify whether 22qDS participants fail to
      show expected patterns of age-related improvements on these tasks; and 2)
      determine whether social cognition better predicts positive and negative symptoms
      than does non-social cognition. Task domains assessed were: emotion recognition
      and differentiation, Theory of Mind (ToM), verbal knowledge, visuospatial skills,
      working memory, and processing speed. Positive and negative symptoms were
      measured using scores obtained from the Structured Interview for Prodromal
      Symptoms (SIPS). 22qDS participants (N=31, mean age: 15.9) showed the largest
      impairment, relative to healthy controls (N=31, mean age: 15.6), on measures of
      ToM and processing speed. In contrast to controls, 22qDS participants did not
      show age-related improvements on measures of working memory and verbal knowledge.
      Notably, ToM performance was the best predictor of positive symptoms in 22qDS,
      accounting for 39% of the variance in symptom severity. Processing speed emerged
      as the best predictor of negative symptoms, accounting for 37% of the variance in
      symptoms. Given that ToM was a robust predictor of positive symptoms in our
      sample, these findings suggest that social cognition may be a valuable
      intermediate trait for predicting the development of psychosis.

PMID- 23122743
TI  - Multiple leiomyosarcoma foci in 18F-FDG PET-CT.

PMID- 23122744
TI  - 18F FDG PET/CT in a child with gliomatosis cerebri.

PMID- 23122745
TI  - [Assessment of overweight from prepuberty to adolescence].
AB  - OBJECTIVE: To examine whether prepubertal overweight continues into adolescence,
      and to evaluate if this progression over time differs by sex. METHODS: The sample
      population consisted of 179 healthy boys and 206 girls on whom anthropometric
      data were assessed at 6-8 years and 13-16 years of age. The assessment of
      overweight was performed according to the cut-offs points of the International
      Obesity Task Force. RESULTS: From baseline to follow-up, the percentage of
      participants who were overweight increased from 23% to 29.2% in males, and
      decreased from 32.6% to 21.4% in females. Baseline weight was significantly
      correlated (P<.01) with follow-up weight in both males (r=0.78) and females
      (r=0.68). Weight and BMI at 6-to-8 years- old explained percentages of variation
      of weight and BMI at 13-to-16 years-old, higher in boys than in girls (64.1% and
      44.1%, respectively, for weight; 53.5% and 39.9%, respectively, for BMI). A total
      of 75% of the participants remained in the same weight category. CONCLUSION: The
      prevalence of overweight in adolescence decreased in girls. The weight and BMI at
      prepubertal age account for a significant percentage of the variation in weight
      and BMI in adolescence. This percentage is higher in males than in females.

PMID- 23122746
TI  - Comments to "The astonishing hypothesis" by Niels de Fine Olivarius (NdFO).

PMID- 23122747
TI  - MRI of persistent cloaca: can it substitute conventional imaging?
AB  - PURPOSE: To define the role of MRI in the preoperative assessment of patients
      with persistent cloaca and whether it can substitute other imaging modalities.
      METHODS: We prospectively examined eleven patients with persistent cloaca between
      July 2007 and March 2012. Non contrast MRI examinations were performed on 1.5T
      magnet using head coil. Multiple pulse sequences (T1WI, T2WI, fat suppression)
      were obtained in axial, sagittal and coronal planes of the pelvis, abdomen, and
      spine. The scans were reviewed for the following: the level and type of rectal
      termination, the developmental state of striated muscle complex (SMC), associated
      genitourinary and spinal anomalies. MRI findings were compared to conventional
      fluoroscopic imaging, operative and endoscopic findings. We applied novel MRI
      parameters (urethral length, relative hiatal distance and vaginal volume). The
      relation between different parameters was tested statistically using Pearson
      correlation test. RESULTS: MRI could accurately demonstrate the level of bowel
      termination in patients with persistent cloaca, in addition to its high
      sensitivity for detection of mullerian anomalies which were present in 73% of
      patients. Furthermore, MRI could disclose associating renal and spinal anomalies,
      and assess the developmental state of SMC. The shorter the urethra (higher
      urogenital confluence), the narrower the pelvic hiatus, and the more was the
      obstruction (vaginal distension). CONCLUSION: MRI is a valuable tool in exploring
      the different internal anatomical features of the cloacal anomaly; and when
      combined with endoscopy, MRI can make other preoperative conventional imaging
      unnecessary.

PMID- 23122748
TI  - Locally advanced rectal cancer: value of ADC mapping in prediction of tumor
      response to radiochemotherapy.
AB  - PURPOSE: To evaluate the diagnostic performance of quantitative apparent
      diffusion coefficient (ADC) measurements, in the assessment of the therapeutic
      response to chemo-radiation therapy (CRT) in patients with locally advanced
      rectal cancer, by analyzing post CRT values of ADC, in relation to tumor
      regression grade (TRG) obtained by histopathologic evaluation of the rectal
      specimen. METHODS: This prospective study was approved by an Institutional Review
      Board, and informed consent was obtained from all patients. Thirty-one patients
      with locally advanced rectal cancer underwent pre and post CRT MR imaging at
      1.5T. ADC values were measured in regions of interest (ROIs) drawn independently
      by two radiologists, blinded to the pathology results, on three slices of the pre
      and post CRT DW-MR image sets with the corresponding T2 weighted images (T2WI)
      available for anatomic reference. The two readers' measurements were compared for
      differences in ADC values, inter-observer variability (measured as the intraclass
      correlation coefficient; ICC) and the ADC distributions of responders vs non
      responders. The diagnostic performance of ADC in the prediction of the response
      to CRT was evaluated by calculating the area under the ROC curve (AUC) and the
      optimal cut-off values. Sensitivity, specificity, positive predictive value
      (PPV), and negative predictive value (NPV) were assessed. RESULTS: The two
      readers showed an overall strong agreement in measuring ADC values. For both
      readers, no differences in ADC pre-treatment measurements were observed between
      responders and non-responders. For reader 1, the post-CRT ADC and the DeltaADC
      presented the higher AUC (0.823 and 0.803, respectively), while Delta%ADC
      provided the lower AUC value (0.682). The optimal cutoff point was 1.294 s/mm(2)
      for post-CRT measures (sensitivity=86.4%, specificity=66.7%, PPV=86.4%,
      NPV=66.7%), 0.500 for DeltaADC (sensitivity=81.8%, specificity=66.7%, PPV=85.7%,
      NPV=60.0%) and 59.3% for Delta%ADC (sensitivity=63.4%, specificity=66.7,
      PPV=82.4%, NPV=42.9%). Similar results were observed for reader 2, with better
      performance obtained with the ADC post-CRT (AUC of 0.833) and an optimal cut off
      of 1.277 * 10(-3)s/mm(2). CONCLUSION: Post-CRT ADC measurements are reliable and
      reproducible and may be used as a non-invasive tool to evaluate response to
      therapy as post-CRT ADC values and DeltaADC presented good diagnostic performance
      to select responder patients.

PMID- 23122749
TI  - Screen printing of solder resist as master substrates for fabrication of multi
      level microfluidic channels and flask-shaped microstructures for cell-based
      applications.
AB  - Although silicon technology can be adopted for the fabrication of microfluidic
      devices with high precision, the capital and operating costs for such technology
      is often prohibitively expensive. In recent years, many alternative methods have
      been advocated to reduce the cost of microfabrication but often with reduced
      qualities in many important features, such as channel resolution, surface
      smoothness and aspect ratio. In this study, we have developed a microfabrication
      method that retains high channel quality and aspect ratio by exploring a rarely
      used solder resist material in combination with screen printing technique to
      generate masters where PDMS-based microfluidic devices could be fabricated by
      replica molding from the masters. Using screen printing, different channel
      heights from 5 to 60 MUm on the master were prepared by varying mesh density,
      controlling solder resist viscosity, and/or adjusting the off-contact gap between
      a mesh and a substrate, while the entire master fabrication process was completed
      within 3 h. This simple, low-cost method could generate fine channel features (50
      MUm) and high aspect ratio (2:1) structures. Microfluidic devices with multi
      level structure could be fabricated by multi-steps photolithography using this
      approach. Moreover, the properties of solder resist enabled the fabrication of
      flask-shaped well structures by controlled partial exposure and development in a
      single-step of photolithography, which was potentially used as cell holding
      reservoirs for cell quantification and cell culture. We believe this fabrication
      method can be easily adopted by other laboratories to conduct microfluidic
      researches without specialized equipment.

PMID- 23122750
TI  - A novel solid-state electrochemiluminescence sensor for melamine with
      Ru(bpy)3(2+)/mesoporous silica nanospheres/Nafion composite modified electrode.
AB  - A novel melamine electrochemiluminescence (ECL) sensor was developed based on
      mesoporous SiO(2) nanospheres/Ru(bpy)(3)(2+)/Nafion modified electrodes. The
      homogeneous mesoporous silica nanospheres, synthesized using modified Stober sol
      gel process, were characterized by Field Emission Scanning Electron Microscopy
      (FE-SEM), Transmission Electron Microscopy (TEM) and Brunauer-Emmett-Teller
      (BET). The ECL and electrochemistry of the modified electrodes were investigated
      with tri-n-propylamine (TPA) as the coreactant. Furthermore, the mesporous SiO(2)
      nanospheres/Ru(bpy)(3)(2+)-based modified electrodes were used for ECL
      determination of melamine. The analytical performances of this ECL sensor for
      melamine based on its enhancement ECL emission of Ru(bpy)(3)(2+) were
      investigated. The results indicated that the sensor exhibited excellent
      performance during melamine determination with a wide linear range (7.81*10(-9)
      5*10(-6) M), low detection limit (2.6*10(-9) M). The high sensitivity and
      stability mainly resulted from the high surface area and special structure of the
      mesoporous silica nanospheres. The proposed ECL approach was used to analyze the
      melamine content in powdered milk with satisfactory results.

PMID- 23122751
TI  - A novel electrochemiluminescence ethanol biosensor based on tris(2,2'-bipyridine)
      ruthenium (II) and alcohol dehydrogenase immobilized in graphene/bovine serum
      albumin composite film.
AB  - We developed a novel electrochemiluminescence (ECL) ethanol biosensor based on
      Ru(bpy)(3)(2+) and alcohol dehydrogenase (ADH) immobilized by graphene/bovine
      serum albumin composite film. The graphene film was directly formed on a glassy
      carbon electrode surface via an in situ reduction of graphene oxide (GO) and
      Ru(bpy)(3)(2+) was immobilized during its formation. The graphene film acted as
      both a decorating agent for immobilization of Ru(bpy)(3)(2+) and a matrix to
      immobilize bovine serum albumin (BSA), meanwhile BSA not only acted as a
      reductant to reduce GO, but also provided a friendly environment for ADH
      immobilization. Furthermore, ADH was separated from Ru(bpy)(3)(2+) by the
      electron-conductive graphene/BSA composite film to retain its enzymatic activity.
      The experimental results indicated that the biosensor had excellent
      electrochemical activity, ECL response to ethanol and stability. Such a design of
      Ru(bpy)(3)(2+)-graphene/BSA film to modify electrode holds a great promise as a
      new biocompatible platform for the development of enzyme-based ECL biosensors.

PMID- 23122752
TI  - The early diagnosis and fast detection of blast fungus, Magnaporthe grisea, in
      rice plant by using its chitinase as biochemical marker and a rice cDNA encoding
      mannose-binding lectin as recognition probe.
AB  - As one of the most destructive and widespread disease of rice, Magnaporthe grisea
      (M. grisea) has a significant negative impact on rice production. Therefore, it
      is significant to develop a method for sensitive and high-throughput detection of
      M. grisea in order to help farmers to find and control blast in the early stage.
      We herein first cloned and expressed the M. grisea's chitinases (Mgchi) and a
      rice cDNA encoding mannose-binding jacalin-related lectin (Osmbl) with Mgchi
      related gene. We demonstrated that Mgchi could be used as a biochemical marker
      for the detection of M. grisea and there was a specific interaction between Osmbl
      and Mgchi. Using Mgchi as biochemical marker and Osmbl as recognition probe, we
      developed a visual method for the specific and sensitive detection of M. grisea
      based on the PdNPs-catalyzed TMB/H(2)O(2) system. The proposed method could be
      used to detect Mgchi as low as 7.5*10(-9) M by naked eye observation and 2.5*10(
      11) M Mgchi by the micro-plate reader. With the help of the method, we had
      successfully detected M. grisea in the real M. grisea-infected rice plant with
      recoveries of 88-109% and RSD<7%. The proposed method was sensitive, specific,
      potentially high-throughput and cost-effective. The success in this study
      provides a promising substitution for the early diagnosis and fast screening of
      M. grisea in rice plant.

PMID- 23122754
TI  - Microbial fuel cell as power supply for implantable medical devices: a novel
      configuration design for simulating colonic environment.
AB  - This study focused on providing power for implantable medical devices (IMDs)
      using a microbial fuel cell (MFC) implanted in human transverse colon.
      Considering the condition of colonic environment, a continuous-flow single
      chamber MFC without membrane was set up. The performance of the MFC was
      investigated. The power output of 1.6 mW under the steady state was not rich
      enough for some high energy-consuming IMDs. Moreover, the parameters of the
      simulated colonic environment, such as pH and ORP value, varied along with the
      time. Hence, a new MFC configuration was developed. In this novel model, pH
      transducers were placed in cathodic and anodic areas, so as to regulate the
      reactor operation timely via external intervention. And two ORP transducers were
      inserted next to the pH transducers, for monitoring and adjusting the MFC
      operation efficiently. Besides, colonic haustra were designed in order to
      increase the difference between cathodic and anodic areas.

PMID- 23122753
TI  - Preparation, characterization of Fe3O4 at TiO2 magnetic nanoparticles and their
      application for immunoassay of biomarker of exposure to organophosphorus
      pesticides.
AB  - Novel Fe(3)O(4) at TiO(2) magnetic nanoparticles were prepared and developed for
      a new nanoparticle-based immunosensor for electrochemical quantification of
      organophosphorylated butyrylcholinesterase (BChE) in plasma, a specific biomarker
      of exposure to organophosphorus (OP) agents. The Fe(3)O(4) at TiO(2)
      nanoparticles were synthesized by hydrolysis of tetrabutyltitanate on the surface
      of Fe(3)O(4) magnetic nanospheres, and characterized by attenuated total
      reflection Fourier-transform infrared spectra, transmission electron microscope
      and X-ray diffraction. The functional Fe(3)O(4) at TiO(2) nanoparticles were
      performed as capture antibody to selectively enrich phosphorylated moiety instead
      of phosphoserine antibody in the traditional sandwich immunoassays. The secondary
      recognition was performed by quantum dots (QDs)-tagged anti-BChE antibody (QDs
      anti-BChE). With the help of a magnet, the resulting sandwich-like complex,
      Fe(3)O(4) at TiO(2)/OP-BChE/QDs-anti-BChE, was easily isolated from sample
      solutions and the released cadmium ions were detected on a disposable screen
      printed electrode (SPE). The binding affinities were investigated by both surface
      plasmon resonance (SPR) and square wave voltammetry (SWV). This method not only
      avoids the drawback of unavailability of commercial OP-specific antibody but also
      amplifies detection signal by QDs-tags together with easy separation of samples
      by magnetic forces. The proposed immunosensor yields a linear response over a
      broad OP-BChE concentrations range from 0.02 to 10 nM, with detection limit of
      0.01 nM. Moreover, the disposable nanoparticle-based immunosensor has been
      validated with human plasma samples. It offers a new method for rapid, sensitive,
      selective and inexpensive screening/evaluating exposure to OP pesticides and
      nerve agents.

PMID- 23122755
TI  - An amperometric biosensor for the detection of hydrogen peroxide released from
      human breast cancer cells.
AB  - The rapid, accurate and sensitive determination of hydrogen peroxide (H(2)O(2))
      is of great significance in the physiological, pathological and environmental
      fields. In this work, we have proposed a highly sensitive and selective
      amperometric biosensor for the detection of extracellular H(2)O(2) released from
      human breast cancer cells with the help of a sequence-specific peptide. Since the
      peptide immobilized on the electrode surface can specifically bind with
      horseradish peroxidase (HRP) in a favorable orientation, which then well promotes
      the catalytic activities of the immobilized enzyme toward the reaction of o
      phenylenediamine and H(2)O(2), the proposed biosensor can detect H(2)O(2) in a
      wide linear range from 1.0*10(-7) M to 1.0*10(-4) M with a low detection limit of
      3.0*10(-8) M. It can be also directly used to efficiently trace extracellular
      H(2)O(2) released from human breast cancer cells MCF-7. Furthermore, the
      reproducibility, stability and selectivity of the biosensor are also quite well
      compared with the previous report, so our biosensor might be potentially useful
      in physiological and pathological detection of H(2)O(2) in the future.

PMID- 23122756
TI  - Construction of DNA-templated nanoparticle assemblies using click DNA ligation.
AB  - We report a simple and versatile strategy for the construction of DNA-templated
      nanoparticle (NP) assemblies using click DNA ligation. Diels-Alder cycloaddition
      reaction of maleic acid and sorbic acid is used for click DNA ligation. Sorbic
      acid-prelabelled DNA nanowires with micron-scale length were synthesized and
      acted as templates for the construction of NP assemblies. Au NPs were orderly
      assembled onto the DNA nanowires using the click DNA ligation to form DNA
      templated Au NP chains. Furthermore, DNA-templated CdTe quantum dot (QD) chains
      were synthesized using the method and characterized by confocal fluorescence
      microscopy (CFM). The DNA-templated CdTe QD chains were functionalized with cell
      binding aptamer as the recognition element. The aptamer-functionalized CdTe QD
      chains, acting as a novel linear-shaped cellular probe, could be used for cancer
      cell imaging. Target cells could be rapidly and easily distinguished from a
      mixture of multiple cells using the cellular probe. The click DNA ligation method
      offers a convenient and efficient way to synthesize DNA-templated NP assemblies,
      and may become a powerful tool in other DNA-based studies.

PMID- 23122758
TI  - The diabetic immigrant: cardiovascular risk factors and control. Contributions of
      the IDIME study.
AB  - INTRODUCTION AND OBJECTIVES: The aim of this study was to determine the clinical
      characteristics of diabetes and associated cardiovascular risk factors in
      immigrants with diabetes in Spain. METHODS: A multicenter, observational, cross
      sectional study including a cohort of 605 diabetic immigrants and 307 native
      diabetics was conducted in patients diagnosed with diabetes and treated in
      primary and specialized care in Spain. A consecutive sampling method was
      followed. We studied epidemiological, clinical and laboratory variables related
      to diabetes and the presence of classical risk factors. RESULTS: The immigrant
      diabetic patient was younger (50.4 [11.5] vs 62.7 [13] years) and had fewer years
      of diabetes progression (5.8 [6.4] vs 10.5 [8.3] years) (P<.001) compared with
      native diabetic patients. Immigrants from South America with diabetes were more
      obese. No statistically significant differences were found in abdominal obesity
      or the waist/height ratio. Glycemic control was worse in immigrants than in the
      native Spaniard group (glycosylated hemoglobin, 7.8 [2.2] vs 7.1 [1.5%]),
      especially among South Asians (8.1[2.5%]) (P<.001), in whom insulin use was lower
      (12.8% vs 30.7% in other immigrants) (P<.001). However, the prevalence of chronic
      complications of diabetes was lower among immigrants, particularly that of
      macrovascular complications (7.7% vs 24.4%) (P<.01). CONCLUSIONS: In our study
      the profile of immigrant diabetics in Spain is one of a young diabetic without
      complications, but with worse metabolic control. These findings provide an
      excellent opportunity to implement preventive measures.

PMID- 23122760
TI  - The pediatric sibling donor experience in hematopoietic stem cell transplant: an
      integrative review of the literature.
AB  - This integrative review explored and described published research findings
      focused on the experiences of pediatric sibling hematopoietic stem cell donors.
      After a comprehensive search, nine studies met the inclusion criteria of the
      study. There was no evidence of coordinated programs of research to effectively
      advance and build knowledge about the experiences of pediatric sibling donors.
      The limited descriptive evidence revealed that differences in the experiences of
      sibling donors vary by age and developmental stages; however, the use of small or
      repeated samples and qualitative methods limited the generalizability of study
      findings. Collaborative research using prospective, longitudinal designs will
      build and advance the evidence base for the design of developmentally appropriate
      interventions for pediatric sibling donors and their families.

PMID- 23122759
TI  - VeriStrat(r) has a prognostic value for patients with advanced non-small cell
      lung cancer treated with erlotinib and bevacizumab in the first line: pooled
      analysis of SAKK19/05 and NTR528.
AB  - BACKGROUND: VeriStrat((r)) is a serum proteomic test used to determine whether
      patients with advanced non-small cell lung cancer (NSCLC) who have already
      received chemotherapy are likely to have good or poor outcomes from treatment
      with gefitinib or erlotinib. The main objective of our retrospective study was to
      evaluate the role of VS as a marker of overall survival (OS) in patients treated
      with erlotinib and bevacizumab in the first line. PATIENTS AND METHODS: Patients
      were pooled from two phase II trials (SAKK19/05 and NTR528). For survival
      analyses, a log-rank test was used to determine if there was a statistically
      significant difference between groups. The hazard ratio (HR) of any separation
      was assessed using Cox proportional hazards models. RESULTS: 117 patients were
      analyzed. VeriStrat classified patients into two groups which had a statistically
      significant difference in duration of OS (p = 0.0027, HR = 0.480, 95% confidence
      interval: 0.294-0.784). CONCLUSION: VeriStrat has a prognostic role in patients
      with advanced, nonsquamous NSCLC treated with erlotinib and bevacizumab in the
      first line. Further work is needed to study the predictive role of VeriStrat for
      erlotinib and bevacizumab in chemotherapy-untreated patients.

PMID- 23122761
TI  - Brief report: a comparison of saliva collection methods with preschool children:
      the perspectives of children, parents, and childcare practitioners.
AB  - Saliva offers developmental researchers and pediatric clinicians significant
      opportunities to measure numerous biological markers. However, many preschool
      aged children refuse to participate in saliva collection. Identifying collection
      methods known to be acceptable to participants may help in maximizing
      participation. To this end, this study aimed to determine the relative
      acceptability of three different collection methods (passive drool,
      hydrocellulose microsponges, and polymer swabs) to children and their caregivers.
      Interviews were carried out with 15 preschool children (age range 32-66 months,
      M=43.65, SD=8.45), their parents, and childcare practitioners. Although children
      reported no overall preference for a specific method, parents and practitioners
      selected hydrocellulose microsponges most often as their preferred method.

PMID- 23122762
TI  - More on prolonged pacifier usage and risk of dental problems: an Italian survey
      of current clinical practice.

PMID- 23122763
TI  - Molecularly imprinted polymer for selective extraction of malachite green from
      seawater and seafood coupled with high-performance liquid chromatographic
      determination.
AB  - In this paper, a highly selective sample cleanup procedure combining molecular
      imprinting technique (MIT) and solid-phase extraction (SPE) was developed for the
      isolation of malachite green in seawater and seafood samples. The molecularly
      imprinted polymer (MIP) was prepared using malachite green as the template
      molecule, methacrylic acid as the functional monomer and ethylene glycol
      dimethacrylate as the cross-linking monomer. The imprinted polymer and non
      imprinted polymer were characterized by scanning electron microscope and static
      adsorption experiments. The MIP showed a high adsorption capacity and was used as
      selective sorbent for the SPE of malachite green. An off-line molecularly
      imprinted solid-phase extraction (MISPE) method followed by high-performance
      liquid chromatography with diodearray detection for the analysis of malachite
      green in seawater and seafood samples was also established. Finally, five samples
      were determined. The results showed that malachite green concentration in one
      seawater sample was at 1.30 MUg L-1 and the RSD (n=3) was 4.15%.

PMID- 23122764
TI  - Response by Kroon.

PMID- 23122765
TI  - Multiple environmental factors influence the spatial distribution and structure
      of reef communities in the northeastern Arabian Peninsula.
AB  - Multivariate analysis revealed distinct sub-regional coral communities among the
      southern Persian Gulf, Strait of Hormuz, and Gulf of Oman. Differences in
      community structure among locations were associated with considerable spatial
      heterogeneity in oceanic conditions, and strong directional environmental
      gradients. Despite clear community differences, considerable changes to coral
      community structure have occurred throughout the northeastern Arabian Peninsula
      as compared with previous studies. The most dramatic of these are the apparent
      changes from Acropora dominated to poritid and faviid dominated communities,
      particularly in the southern Persian Gulf and Strait of Hormuz. Although
      temperature and salinity have previously been cited as the major environmental
      factors structuring coral communities around the region, additional environmental
      parameters, including chlorophyll-a, surface currents and winds are shown to be
      important in structuring reef communities throughout the northeastern Arabian
      Peninsula. 

PMID- 23122766
TI  - Effect of sewage nutrients on algal production, biomass and pigments in tropical
      tidal creeks.
AB  - Microalgal blooms can result from anthropogenic nutrient loadings in coastal
      ecosystems. However, differentiating sources of nutrients remains a challenge.
      The response of phytoplankton and benthic microalgae (BMA) to nutrient loads was
      compared across tropical tidal creeks with and without secondary treated sewage.
      Primary productivity in the water column was limited by nitrogen availability in
      absence of sewage, with nitrogen saturation in the presence of sewage.
      Phytoplankton primary productivity rates and chlorophyll a concentrations
      increased in response to sewage, and there was a greater response than for BMA.
      There was no change in algal pigment proportions within the phytoplankton or BMA
      communities. Concentrations of the sewage marker, coprostanol, were higher near
      sewage discharge points decreasing downstream, correlating with a decline in
      nutrient concentrations. This suggests that sewage was the main source of
      nitrogen and phosphorus. This study highlights the scale and type of response of
      algal communities to sewage nutrients.

PMID- 23122767
TI  - Lomitapide for homozygous familial hypercholesterolaemia.

PMID- 23122769
TI  - A young woman with a first-time seizure and a huge intracranial vascular
      structure.

PMID- 23122768
TI  - Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in
      patients with homozygous familial hypercholesterolaemia: a single-arm, open
      label, phase 3 study.
AB  - BACKGROUND: Patients with homozygous familial hypercholesterolaemia respond
      inadequately to existing drugs. We aimed to assess the efficacy and safety of the
      microsomal triglyceride transfer protein inhibitor lomitapide in adults with this
      disease. METHODS: We did a single-arm, open-label, phase 3 study of lomitapide
      for treatment of patients with homozygous familial hypercholesterolemia. Current
      lipid lowering therapy was maintained from 6 weeks before baseline through to at
      least week 26. Lomitapide dose was escalated on the basis of safety and
      tolerability from 5 mg to a maximum of 60 mg a day. The primary endpoint was mean
      percent change in levels of LDL cholesterol from baseline to week 26, after which
      patients remained on lomitapide through to week 78 for safety assessment. Percent
      change from baseline to week 26 was assessed with a mixed linear model. FINDINGS:
      29 men and women with homozygous familial hypercholesterolaemia, aged 18 years or
      older, were recruited from 11 centres in four countries (USA, Canada, South
      Africa, and Italy). 23 of 29 enrolled patients completed both the efficacy phase
      (26 weeks) and the full study (78 weeks). The median dose of lomitapide was 40 mg
      a day. LDL cholesterol was reduced by 50% (95% CI -62 to -39) from baseline (mean
      8.7 mmol/L [SD 2.9]) to week 26 (4.3 mmol/L [2.5]; p<0.0001). Levels of LDL
      cholesterol were lower than 2.6 mmol/L in eight patients at 26 weeks.
      Concentrations of LDL cholesterol remained reduced by 44% (95% CI -57 to -31;
      p<0.0001) at week 56 and 38% (-52 to -24; p<0.0001) at week 78. Gastrointestinal
      symptoms were the most common adverse event. Four patients had aminotransaminase
      levels of more than five times the upper limit of normal, which resolved after
      dose reduction or temporary interruption of lomitapide. No patient permanently
      discontinued treatment because of liver abnormalities. INTERPRETATION: Our study
      suggests that treatment with lomitapide could be a valuable drug in the
      management of homozygous familial hypercholesterolaemia. FUNDING: FDA Office of
      the Orphan Product Development, Aegerion Pharmaceuticals.

PMID- 23122772
TI  - Chemical taxonomy of red-flowered wild Camellia species based on floral
      anthocyanins.
AB  - This study uses anthocyanins in the red flowers of section Camellia as taxonomic
      markers to investigate the phenetic relationships among 33 wild species from
      China, Taiwan, and Japan. The 25 anthocyanins from section Camellia produced 38
      pigment patterns that serve as phenetic markers. Principal Component Analysis
      (PCA) indicated that the attachment of one or two glucoses to the cyanidin-core
      structure at the 3- or the 3- and 5-positions, respectively, was the most
      influential pattern against the first factor, Z1. In addition, two alternative
      pigment patterns, acylated or non-acylated, and the structural isomerism (cis- or
      trans-) of the p-coumaroyl group were relatively significant patterns. Ward's
      minimum-variance cluster analysis (WMVCA) produced a dendrogram that consisted of
      two sub-clusters. One sub-cluster (A) was constructed by species that have mainly
      two types of anthocyanins: 3,5-di-O-beta-glucosides (Camellia saluenensis) and
      sambubioside of cyanidin (Camellia reticulata). The other sub-cluster (B) was
      made up of the 3-O-beta-glucosides of cyanidin (Camellia japonica) and
      delphinidin (Camellia hongkongensis), with a higher proportion of the 3-O-beta
      galactosides (Camellia mairei and Camellia boreali-yunnanica). The former group
      showed a higher proportion of acylation, over 63%, but with the exception of
      Camellia azalea. The latter group showed less than 52% acylation, but with the
      exception of C. hongkongensis and C. boreali-yunnanica. PCA and WMVCA indicated
      that the greater the amount of di-O-glycosides and acylation, the more primitive
      anthocyanin traits the species possess. Based on these results, in conjunction
      with geographical and literary information, the data suggest that the Xinan
      district is the site/center of origin for the red-flowered Camellia species of
      which both C. saluenensis and C. reticulata have the most primitive anthocyanin
      traits.

PMID- 23122771
TI  - Reducing methylmercury accumulation in the food webs of San Francisco Bay and its
      local watersheds.
AB  - San Francisco Bay (California, USA) and its local watersheds present an
      interesting case study in estuarine mercury (Hg) contamination. This review
      focuses on the most promising avenues for attempting to reduce methylmercury
      (MeHg) contamination in Bay Area aquatic food webs and identifying the scientific
      information that is most urgently needed to support these efforts. Concern for
      human exposure to MeHg in the region has led to advisories for consumption of
      sport fish. Striped bass from the Bay have the highest average Hg concentration
      measured for this species in USA estuaries, and this degree of contamination has
      been constant for the past 40 years. Similarly, largemouth bass in some Bay Area
      reservoirs have some of the highest Hg concentrations observed in the entire US.
      Bay Area wildlife, particularly birds, face potential impacts to reproduction
      based on Hg concentrations in the tissues of several Bay species. Source control
      of Hg is one of the primary possible approaches for reducing MeHg accumulation in
      Bay Area aquatic food webs. Recent findings (particularly Hg isotope
      measurements) indicate that the decades-long residence time of particle
      associated Hg in the Bay is sufficient to allow significant conversion of even
      the insoluble forms of Hg into MeHg. Past inputs have been thoroughly mixed
      throughout this shallow and dynamic estuary. The large pool of Hg already present
      in the ecosystem dominates the fraction converted to MeHg and accumulating in the
      food web. Consequently, decreasing external Hg inputs can be expected to reduce
      MeHg in the food web, but it will likely take many decades to centuries before
      those reductions are achieved. Extensive efforts to reduce loads from the largest
      Hg mining source (the historic New Almaden mining district) are underway. Hg is
      spread widely across the urban landscape, but there are a number of key sources,
      source areas, and pathways that provide opportunities to capture larger
      quantities of Hg and reduce loads from urban runoff. Atmospheric deposition is a
      lower priority for source control in the Bay Area due to a combination of a lack
      of major local sources. Internal net production of MeHg is the dominant source of
      MeHg that enters the food web. Controlling internal net production is the second
      primary management approach, and has the potential to reduce food web MeHg in
      some habitats more effectively and within a much shorter time-frame. Controlling
      net MeHg production and accumulation in the food web of upstream reservoirs and
      ponds is very promising due to the many features of these ecosystems that can be
      manipulated. The most feasible control options in tidal marshes relate to the
      design of flow patterns and subhabitats in restoration projects. Options for
      controlling MeHg production in open Bay habitat are limited due primarily to the
      highly dispersed distribution of Hg throughout the ecosystem. Other changes in
      these habitats may also have a large influence on food web MeHg, including
      temperature changes due to global warming, sea level rise, food web alterations
      due to introduced species and other causes, and changes in sediment supply. Other
      options for reducing or mitigating exposure and risk include controlling
      bioaccumulation, cleanup of contaminated sites, and reducing other factors (e.g.,
      habitat availability) that limit at-risk wildlife populations.

PMID- 23122773
TI  - Guatemalan potato moth Tecia solanivora distinguish odour profiles from
      qualitatively different potatoes Solanum tuberosum L.
AB  - Guatemalan potato moth, Tecia solanivora, lay eggs in the soil nearby potato
      Solanum spp. and larvae feed on the tubers. We investigated the oviposition
      behaviour of T. solanivora females and the survival of larval offspring on
      healthy vs. stressed, i.e. light exposed and/or damaged potato tubers. In choice
      tests, females laid significantly more eggs in response to potato odour of
      healthy tubers and female oviposition preference correlated with higher larval
      survival. Survival of larvae was negatively correlated with the tuber content of
      the steroid glycoalkaloids alpha-solanine and alpha-chaconine: healthy potatoes
      contained lower amounts than stressed tubers, ranging from 25 to 500 MUg g-1 and
      from 30 to 600 MUg g-1, respectively. Analysis of volatile compounds emitted by
      potato tubers revealed that stressed tubers could clearly be distinguished from
      healthy tubers by the composition of their volatile profiles. Compounds that
      contributed to this difference were e.g. decanal, nonanal, isopropyl myristate,
      phenylacetaldehyde, benzothiazole, heptadecane, octadecane, myristicin, E,E-alpha
      farnesene and verbenone. Oviposition assays, when female moths were not in
      contact with the tubers, clearly demonstrated that volatiles guide the females to
      lay fewer eggs on stressed tubers that are of inferior quality for the larvae. We
      propose that volatiles, such as sesquiterpenes and aldehydes, mediate oviposition
      behaviour and are correlated with biosynthetically related, non-volatile
      compounds, such as steroidal glycoalkaloids, which influence larval survival. We
      conclude that the oviposition response and larval survival of T. solanivora on
      healthy vs. stressed tubers supports the preference performance hypothesis for
      insect herbivores.

PMID- 23122774
TI  - Mortality following treatment for cannabis use disorders: predictors and causes.
AB  - The aim of the study was to determine excess mortality associated with cannabis
      use disorders. Individuals entering treatment for cannabis use disorders were
      followed by use of Danish registers and standardized mortality ratios (SMRs)
      estimated. Predictors of different causes of death were determined. A total of
      6445 individuals were included and 142 deaths recorded during 26,584 person-years
      of follow-up. Mortality was predicted by age, comorbid use of opioids, and
      lifetime injection drug use. For different causes of death the SMRs were:
      accidents: 8.2 (95% CI 6.3-10.5), suicide: 5.3 (95% CI 3.3-7.9),
      homicide/violence: 3.8 (95% CI 1.5-7.9), and natural causes: 2.8 (95% CI 2.0
      3.7). Following exclusion of those with secondary use of opioids, cocaine,
      amphetamine, or injection drug use, SMRs for all causes of death remained
      significantly elevated except for homicide/violence. The study underlines the
      need to address mortality risk associated with cannabis use disorders.

PMID- 23122770
TI  - Bone mineral density and blood metals in premenopausal women.
AB  - Exposure to metals, specifically cadmium, lead, and mercury, is widespread and is
      associated with reduced bone mineral density (BMD) in older populations, but the
      associations among premenopausal women are unclear. Therefore, we evaluated the
      relationship between these metals in blood and BMD (whole body, total hip, lumbar
      spine, and non-dominant wrist) quantified by dual energy X-ray absorptiometry in
      248 premenopausal women, aged 18-44. Participants were of normal body mass index
      (mean BMI 24.1), young (mean age 27.4), 60% were white, 20% non-Hispanic black,
      15% Asian, and 6% other race group, and were from the Buffalo, New York region.
      The median (interquartile range) level of cadmium was 0.30 MUg/l (0.19-0.43), of
      lead was 0.86 MUg/dl (0.68-1.20), and of mercury was 1.10 MUg/l (0.58-2.00). BMD
      was treated both as a continuous variable in linear regression and dichotomized
      at the 10th percentile for logistic regression analyses. Mercury was associated
      with reduced odds of decreased lumbar spine BMD (0.66, 95% confidence interval:
      0.44, 0.99), but overall, metals at environmentally relevant levels of exposure
      were not associated with reduced BMD in this population of healthy, reproductive
      aged women. Further research is needed to determine if the blood levels of
      cadmium, lead, and mercury in this population are sufficiently low that there is
      no substantive impact on bone, or if effects on bone can be expected only at
      older ages.

PMID- 23122775
TI  - Neuroendocrine control of feeding behavior and psychomotor activity by
      neuropeptideY in fish.
AB  - Neuropeptide Y (NPY) is a neuropeptide distributed widely among vertebrates. In
      mammals, NPY and its related peptides such as pancreatic polypeptide and peptide
      YY (PYY) are distributed throughout the brain and gastrointestinal tissues, and
      are centrally involved in many physiological functions such as the regulation of
      food intake, locomotion and psychomotor activities through their receptors. With
      regard to non-mammalian vertebrates, there has also been intensive study aimed at
      the identification and functional characterization of NPY, PYY and their
      receptors, and recent investigations of the role of NPY have revealed that it
      exerts several behavioral effects in goldfish and zebrafish. Both of these
      species are excellent teleost fish models, in which it has been demonstrated that
      NPY increases food consumption as an orexigenic factor and reduces locomotor
      activity, as is the case in mammals. This paper reviews current knowledge of NPY
      derived from studies of teleost fish, as representative non-mammals, focusing
      particularly on the role of the NPY system, and examines its significance from a
      comparative viewpoint.

PMID- 23122776
TI  - Neuropeptide Y polymorphism increases the risk for asthma in overweight subjects;
      protection from atherosclerosis in asthmatic subjects--the cardiovascular risk in
      young Finns study.
AB  - AIMS: The role of neuropeptide Y (NPY) and its gene polymorphisms in the
      development of atherosclerosis has become increasingly evident. In asthma, NPY
      has been shown to be involved as immunomodulator. In this study, we investigated
      the role of two functional NPY polymorphisms, NPY-Leu7Pro (rs16139) and NPY
      399C/T (rs16147) and obesity for the development of asthma as well as
      atherosclerosis in asthmatic and non-asthmatic subjects. Also, we measured heart
      rate variability (HRV) and NPY in serum since these might contribute through
      these polymorphisms to both diseases. METHODS AND RESULTS: Thousand hundred and
      seventy six Finnish young adults were genotyped and three groups (G1-G3) were
      formed based on the observed diplotypes. The NPY-Pro7 allele always co-existed
      with the NPY-399T allele indicating complete linkage disequilibrium. Here we show
      that overweight (BMI>=25kg/m2) was associated with 2.5-fold increased risk for
      asthma in subjects with the NPY-399T allele without NPY-Pro7 allele (G2, n=716).
      Overweight was also associated with increased atherosclerosis determined by
      carotid intima media thickness (cIMT), but asthma seemed to be more significant
      determinant than overweight in determing cIMT having a decreasing effect. NPY
      concentration in serum was diplotype-driven (G1=792.2(29.5), G2=849.0(18.9),
      G3=873.9(45.2) pg/ml) and correlated positively with cIMT in the group having NPY
      Pro7 allele (G3, n=142). However, the subjects with asthma had a negative NPY
      cIMT relationship. Total HRV was increased in asthma and correlated negatively
      with cIMT irrespective of the NPY genotype. CONCLUSIONS: Overweight together with
      the NPY-399T allele without NPY-Pro7 allele was associated with increased risk
      for asthma. Atherosclerosis was decreased in subjects with asthma depending on
      the NPY genotype. The results reveal novel insights into the genetics and biology
      of the relationship of atherosclerosis and asthma.

PMID- 23122777
TI  - Biophysical characterization of a binding site for TLQP-21, a naturally occurring
      peptide which induces resistance to obesity.
AB  - Recently, we demonstrated that TLQP-21 triggers lipolysis and induces resistance
      to obesity by reducing fat accumulation [1]. TLQP-21 is a 21 amino acid peptide
      cleavage product of the neuroprotein VGF and was first identified in rat brain.
      Although TLQP-21 biological activity and its molecular signaling is under active
      investigation, a receptor for TLQP-21 has not yet been characterized. We now
      demonstrate that TLQP-21 stimulates intracellular calcium mobilization in CHO
      cells. Furthermore, using Atomic Force Microscopy (AFM), we also provide evidence
      of TLQP-21 binding-site characteristics in CHO cells. AFM was used in force
      mapping mode equipped with a cantilever suitably functionalized with TLQP-21.
      Attraction of this functionalized probe to the cell surface was specific and
      consistent with the biological activity of TLQP-21; by contrast, there was no
      attraction of a probe functionalized with biologically inactive analogues. We
      detected interaction of the peptide with the binding-site by scanning the cell
      surface with the cantilever tip. The attractive force between TLQP-21 and its
      binding site was measured, statistically analyzed and quantified at approximately
      40 pN on average, indicating a single class of binding sites. Furthermore we
      observed that the distribution of these binding sites on the surface was
      relatively uniform.

PMID- 23122778
TI  - Modeling the surface of Campylobacter fetus: protein surface layer stability and
      resistance to cationic antimicrobial peptides.
AB  - Campylobacter fetus is a Gram negative bacterium recognized for its virulence in
      animals and humans. This bacterium possesses a paracrystalline array of high
      molecular weight proteins known as surface-layer proteins covering its cell
      surface. A mathematical model has been made of the outer membrane of this
      bacterium, both with its surface-layer proteins (S+) and without (S-). Monte
      Carlo computer simulation was used to understand the stability of the surface
      layer protein structure as a function of ionic concentration. The interactions of
      an electrically-charged antimicrobial agent, the cationic antimicrobial peptide
      protamine, with surface-layer proteins and with the lipopolysaccharides of the
      outer membrane were modeled and analyzed. We found that (1) divalent ions
      stabilize the surface-layer protein array by reducing the fluctuations
      perpendicular and parallel to the membrane plane thereby promoting adhesion to
      the LPS region. This was achieved via (2) divalent ions bridging the negatively
      charged LPS Core. The effect of this bridging is to bring individual Core regions
      closer together so that the O-antigens can (3) increase their attractive van der
      Waals interactions and "collapse" to form a surface with reduced perpendicular
      fluctuations. These findings provide support for the proposal of Yang et al. [1].
      (4) No evidence for a significant increase in Ca(2+) concentration in the region
      of the surface-layer protein subunits was observed in S+ simulations compared to
      S- simulations. (5) We predicted the trends of protamine MIC tests performed on
      C. fetus and these were in good agreement with our experimental results.

PMID- 23122779
TI  - A conserved interdomain communication pathway of pseudosymmetrically distributed
      residues affects substrate specificity of the fungal multidrug transporter Cdr1p.
AB  - Understanding the communication pathways between remote sites in proteins is of
      key importance for understanding their function and mechanism of action. These
      remain largely unexplored among the pleiotropic drug resistance (PDR)
      representatives of the ubiquitous superfamily of ATP-binding cassette (ABC)
      transporters. To identify functionally coupled residues important for the
      polyspecific transport by the fungal ABC multidrug transporter Cdr1p a new
      selection strategy, towards increased resistance to a preferred substrate of the
      homologous Snq2p, was applied to a library of randomly generated mutants. The
      single amino acid substitutions, located pseudosymmetrically in each domain of
      the internally duplicated protein: the H-loop of the N-terminal nucleotide
      binding domain (NBD1) (C363R) and in the C-terminal NBD2 region preceding Walker
      A (V885G). The central regions of the first transmembrane helices 1 and 7 of both
      transmembrane domains were also affected by the G521S/D and A1208V substitutions
      respectively. Although the mutants were expressed at a similar level and located
      correctly to the plasma membrane, they selectively affected transport of multiple
      drugs, including azole antifungals. The synergistic effects of combined mutations
      on drug resistance, drug dependent ATPase activity and transport support the view
      inferred from the statistical coupling analysis (SCA) of aminoacid coevolution
      and mutational analysis of other ABC transporter families that these residues are
      an important part of the conserved, allosterically coupled interdomain
      communication network. Our results shed new light on the communication between
      the pseudosymmetrically arranged domains in a fungal PDR ABC transporter and
      reveal its profound influence on substrate specificity.

PMID- 23122780
TI  - Protocol of the Definition for the Assessment of Time-to-event Endpoints in
      CANcer trials (DATECAN) project: formal consensus method for the development of
      guidelines for standardised time-to-event endpoints' definitions in cancer
      clinical trials.
AB  - INTRODUCTION: In randomised phase III cancer clinical trials, the most
      objectively defined and only validated time-to-event endpoint is overall survival
      (OS). The appearance of new types of treatments and the multiplication of lines
      of treatment have resulted in the use of surrogate endpoints for overall survival
      such as progression-free survival (PFS), or time-to-treatment failure. Their
      development is strongly influenced by the necessity of reducing clinical trial
      duration, cost and number of patients. However, while these endpoints are
      frequently used, they are often poorly defined and definitions can differ between
      trials which may limit their use as primary endpoints. Moreover, this variability
      of definitions can impact on the trial's results by affecting estimation of
      treatments' effects. The aim of the Definition for the Assessment of Time-to
      event Endpoints in CANcer trials (DATECAN) project is to provide recommendations
      for standardised definitions of time-to-event endpoints in randomised cancer
      clinical trials. METHODS: We will use a formal consensus methodology based on
      experts' opinions which will be obtained in a systematic manner. RESULTS:
      Definitions will be independently developed for several cancer sites, including
      pancreatic, breast, head and neck and colon cancer, as well as sarcomas and
      gastrointestinal stromal tumours (GISTs). DISCUSSION: The DATECAN project should
      lead to the elaboration of recommendations that can then be used as guidelines by
      researchers participating in clinical trials. This process should lead to a
      standardisation of the definitions of commonly used time-to-event endpoints,
      enabling appropriate comparisons of future trials' results.

PMID- 23122781
TI  - Exploring the determinants of pedestrian-vehicle crash severity in New York City.
AB  - Pedestrian-vehicle crashes remain a major concern in New York City due to high
      percentage of fatalities. This study develops random parameter logit models for
      explaining pedestrian injury severity levels of New York City accounting for
      unobserved heterogeneity in the population and across the boroughs. A log
      likelihood ratio test for joint model suitability suggests that separate models
      for each of the boroughs should be estimated. Among many variables, road
      characteristics (e.g., number of lanes, grade, light condition, road surface,
      etc.), traffic attributes (e.g., presence of signal control, type of vehicle,
      etc.), and land use (e.g., parking facilities, commercial and industrial land
      use, etc.) are found to be statistically significant in the estimated model. The
      study also suggests that the set of counter measures should be different for
      different boroughs in the New York City and the priority ranks of countermeasures
      should be different as well.

PMID- 23122782
TI  - Time for a low-risk DCIS trial: harnessing public and patient involvement.

PMID- 23122783
TI  - Primary systemic treatment of breast-cancer brain metastases.

PMID- 23122785
TI  - Predicting lymph node metastases in early rectal cancer.
AB  - AIM: In this population-based study, the aim was to investigate risk factors for
      lymph node metastases and to construct a risk stratification index with relevance
      for pre-operative planning in T1 and T2 rectal cancers. METHODS: Data were
      retrieved from The Swedish Rectal Cancer Register, a mandatory, national,
      prospectively collected data base. All T1 and T2 rectal cancers treated with
      abdominal resection surgery without neo-adjuvant or adjuvant radio-chemotherapy
      from 2007 to 2010 were analysed. T-stage, sm-level, histologic differentiation,
      mucinous tumour type, blood vessel- and perineural infiltration, tumour location
      (in cm from the anal verge), age and gender were evaluated as potential
      predictors of lymph node metastases, using uni- and multivariate logistic
      regression. RESULTS: T2-stage (odds ratio [OR]=2.0), poor differentiation
      (OR=6.5) and vascular infiltration (OR=4.3) were identified as significant risk
      factors for lymph node metastases in the multivariate analysis. The risk
      stratification index shows the risk for lymph node metastases gradually
      increasing from 6% to 65% and 11% to 78% in T1 and T2 cancers respectively, when
      adding the risk factors one by one. CONCLUSION: There is a considerable span in
      the risk for lymph node metastases between low risk T1 and high risk T2 rectal
      cancer. Using the risk stratification-model, with the concept of local excision
      as a macro-biopsy with standby for subsequent immediate radical resection surgery
      in high-risk cases, could benefit patients by providing the advantages of local
      excision yet ensuring adequate oncologic outcome.

PMID- 23122784
TI  - Lapatinib plus capecitabine in patients with previously untreated brain
      metastases from HER2-positive metastatic breast cancer (LANDSCAPE): a single
      group phase 2 study.
AB  - BACKGROUND: Brain metastases occur in 30-50% of patients with metastatic HER2
      positive breast cancer. In the case of diffuse brain metastases, treatment is
      based on whole brain radiotherapy (WBRT). Few systemic options are available. We
      aimed to investigate the combination of lapatinib plus capecitabine for the
      treatment of previously untreated brain metastases from HER2-positive breast
      cancer. METHODS: In this single-arm phase 2, open-label, multicentre study,
      eligible patients had HER2-positive metastatic breast cancer with brain
      metastases not previously treated with WBRT, capecitabine, or lapatinib.
      Tretament was given in 21 day cycles: patients received lapatinib (1250 mg,
      orally) every day and capecitabine (2000 mg/m(2), orally) from day 1 to day 14.
      The primary endpoint was the proportion of patients with an objective CNS
      response, defined as a 50% or greater volumetric reduction of CNS lesions in the
      absence of increased steroid use, progressive neurological symptoms, and
      progressive extra-CNS disease. All responses had to be confirmed 4 weeks after
      initial response. Efficacy analyses included all patients who received the study
      drugs and were assessable for efficacy criteria. This trial is registered with
      ClinicalTrials.gov, number NCT00967031. FINDINGS: Between April 15, 2009, to Aug
      2, 2010, we enrolled 45 patients, 44 (98%) of whom were assessable for efficacy,
      with a median follow-up of 21.2 months (range 2.2-27.6). 29 patients had an
      objective CNS response (65.9%, 95% CI 50.1-79.5); all were partial responses. Of
      all 45 treated patients, 22 (49%) had grade 3 or grade 4 treatment-related
      adverse events, of which the most common were diarrhoea in nine (20%) patients
      and hand-foot syndrome in nine (20%) patients. 14 (31%) patients had at least one
      severe adverse event; treatment was discontinued because of toxicity in four
      patients. No toxic deaths occurred. INTERPRETATION: The combination of lapatinib
      and capecitabine is active as first-line treatment of brain metastases from HER2
      positive breast cancer. A phase 3 trial is warranted. FUNDING: GlaxoSmithKline
      France and UNICANCER.

PMID- 23122786
TI  - Balloon cervicoplasty: a simplified technique for correction of isolated cervical
      atresia.
AB  - OBJECTIVES: To test the efficacy, safety and tolerability of a simplified
      surgical alternative for the formation of a new cervix in patients with isolated
      cervical aplasia. STUDY DESIGN: A case series of six patients with complete
      cervical atresia (four primary and two secondary) were included. A silicone Foley
      catheter sutured to the distal end of a sharp curved long inserter was inserted
      laparoscopically, and left in utero inflated and subject to downward traction for
      one menstrual cycle. Clinical and sonographic follow-up were done. The main
      outcome measures were operative time, complication rate, tolerability of
      traction, reintervention rate, width and length of the newly formed cervix and
      postoperative menstrual pattern. RESULTS: The results were satisfactory (normal
      length and width of new cervix by high-resolution 2D ultrasonography), without
      complications, with acceptable tolerability and normal menstrual pattern.
      CONCLUSIONS: Both clinical and sonographic follow-up confirmed that balloon
      cervicoplasty is a simple, fast, tolerable, safe and available laparoscopically
      guided procedure. It can be easily performed by any gynecologist with basic
      laparoscopic expertise.

PMID- 23122787
TI  - Differential subcellular localization, enzymatic properties and expression
      patterns of gamma-aminobutyric acid transaminases (GABA-Ts) in rice (Oryza
      sativa).
AB  - gamma-Aminobutyric acid transaminase (GABA-T) catalyzes the conversion of GABA to
      succinic semialdehyde. The rice (Oryza sativa) genome possesses four putative
      GABA-T genes, which exhibit high amino acid identity (73-82%) but differ in
      length of the N-terminal region. Transient expression of GABA-T-green fluorescent
      fusion proteins in onion epidermal cells demonstrated that two of the four
      enzymes were targeted to mitochondria, a third to chloroplasts, and the fourth to
      cytosol. Enzymatic analysis of three organelle-targeted GABA-Ts revealed that
      they used pyruvate and glyoxylate as amino acceptors and that two of the enzymes
      functioned in mitochondria and chloroplasts at similar levels of activity,
      whereas the second mitochondrial enzyme displayed very low activity.
      Transcriptional analysis demonstrated that two of the four genes were more highly
      expressed in the vegetative organs tested, but exhibited a different pattern
      during seed maturation. Together, these results suggest that members of the rice
      GABA-T gene family vary in many respects, such as intracellular targeting,
      enzymatic activity and regulation of gene expression.

PMID- 23122788
TI  - Arbuscular mycorrhizal fungal inoculation increases phenolic synthesis in clover
      roots via hydrogen peroxide, salicylic acid and nitric oxide signaling pathways.
AB  - Arbuscular mycorrhizal fungi can increase the host resistance to pathogens via
      promoted phenolic synthesis, however, the signaling pathway responsible for it
      still remains unclear. In this study, in order to reveal the signaling molecules
      involved in this process, we inoculated Trifolium repense L. with an arbuscular
      mycorrhizal fungus (AMF), Glomus mosseae, and monitored the contents of phenolics
      and signaling molecules (hydrogen peroxide (H(2)O(2)), salicylic acid (SA), and
      nitric oxide (NO)) in roots, measured the activities of l-phenylalanine ammonia
      lyase (PAL) and nitric oxide synthase (NOS), and the expression of pal and chs
      genes. Results demonstrated that AMF colonization promoted the phenolic
      synthesis, in parallel with the increase in related enzyme activity and gene
      expression. Meanwhile, the accumulation of all three signaling molecules was also
      up-regulated by AMF. This study suggested that AMF increased the phenolic
      synthesis in roots probably via signaling pathways of H(2)O(2), SA and NO in a
      signaling cascade.

PMID- 23122789
TI  - Stimulation of chlororespiration by drought under heat and high illumination in
      Rosa meillandina.
AB  - Rosa meillandina plants were used to study the effects of water deficit on
      photosynthesis and chlororespiration. Plants showed high tolerance to heat and
      high illumination in controlled conditions that ensured that there was no water
      deficit. However, when heat and high illumination were accompanied by low
      watering photosynthetic linear electron transport was down regulated, as
      indicated by the reduced photochemistry efficiency of PS II, which was associated
      with an increase in the non-photochemical quenching of fluorescence. In addition
      to the effects on the photosynthetic activity, changes were also observed in the
      plastidial NDH complex, PTOX and PGR5. In plants exposed to heat and high
      illumination without water deficit, the activities and amounts of the
      chlororespiration enzymes, NDH complex and PTOX, remained similar to the control
      and only increased in response to drought, high light and heat stress, applied
      together. In contrast, both the PS I activity and the amount of PGR5 polypeptide
      were higher in plants exposed to heat and high illumination without water deficit
      than in those with water deficit. The results indicated that in the conditions
      studied, the contribution of chlororespiration to regulating photosynthetic
      electron flow is not relevant when there is no water deficit, and another
      pathway, such as cyclic electron flow involving PGR5 polypeptide, may be more
      important. However, when PS II activity is inhibited by drought,
      chlororespiration, together with other routes of electron input to the electron
      transfer chain, is probably essential.

PMID- 23122790
TI  - Oxidation-specific biomarkers, prospective 15-year cardiovascular and stroke
      outcomes, and net reclassification of cardiovascular events.
AB  - OBJECTIVES: This study sought to assess the long-term predictive value and net
      reclassification for risk of cardiovascular disease (CVD) of biomarkers
      reflecting oxidation-specific epitopes (OSEs). BACKGROUND: OSEs are immunogenic,
      proinflammatory, and proatherogenic. The long-term predictive value and net
      reclassification of OSEs for risk of CVD events are not known. METHODS: Oxidized
      phospholipids on apolipoprotein B-100 (OxPL/apoB) and immunoglobulin (Ig)-G (IgG)
      and IgM autoantibodies to malondialdehyde-modified, low-density lipoprotein (MDA
      LDL) and copper-oxidized LDL (Cu-OxLDL) were measured in 765 subjects in 1995 and
      656 subjects in 2000 in the Bruneck study, representing 45- to 84-year-old men
      and women from the general community. RESULTS: Over 15 years of follow-up, 138
      subjects reached the primary endpoint of incident CVD (ischemic stroke,
      myocardial infarction, new-onset unstable angina, acute coronary interventions,
      and vascular death). In a multivariable Cox model, the highest tertile of
      OxPL/apoB was associated with higher risk of CVD (hazard ratio [HR]: 2.4; 95%
      confidence interval [CI]: 1.5 to 3.7) and stroke (HR: 3.6; 95% CI: 1.8 to 7.4)
      compared with the lowest tertile. IgG Cu-OxLDLs were associated with higher risk
      of CVD, whereas IgM MDA-LDLs were associated with lower risk. Using OxPL/apoB,
      IgG Cu-OxLDL, and IgM MDA-LDL variables, the area under the curve (AUC) for CVD
      risk prediction increased from 0.664 (95% CI: 0.629 to 0.697) to 0.705 (95% CI:
      0.672 to 0.737) (p = 0.048). The net reclassification index (NRI) was 0.163 (p =
      0.0044) and 0.332 (p < 0.0001) in all subjects (n = 765) and in subjects with
      intermediate risk (n = 305), respectively. Of 627 subjects who remained free of
      CVD, 108 were correctly reclassified to a lower risk category, and 83 were
      reclassified to a higher category (categories: 15-year risk <15%, 15% to 30%,
      >30%). CONCLUSIONS: OSE biomarkers predict 15-year CVD and stroke outcomes and
      provide potential clinical utility by reclassifying a significant proportion of
      individuals into higher or lower risk categories after traditional risk
      assessment.

PMID- 23122791
TI  - The subcutaneous implantable cardioverter-defibrillator: should patients want
      one?
AB  - The subcutaneous implantable cardioverter-defibrillator is a novel device that
      does not require insertion of a transvenous lead; rather, it delivers 80-J
      transthoracic shocks via a subcutaneous pulse generator implanted in the left
      lateral chest and a subcutaneous left parasternal lead-electrode. It recently
      received approval by U.S. Food and Drug Administration panel on the basis of a
      180-day study in 330 patients. However, it has not been shown to be non inferior
      to current implantable cardioverter-defibrillators, and it does not provide
      either anti-tachycardia or bradycardia pacing. Thus, is this technology ready for
      widespread application? Specifically, should a patient want one?

PMID- 23122792
TI  - Subcutaneous B-type natriuretic peptide for treatment of heart failure: a dying
      therapy reborn?

PMID- 23122793
TI  - Asymptomatic left ventricular systolic dysfunction in patients with severe aortic
      stenosis: characteristics and outcomes.
AB  - OBJECTIVES: This study sought to determine the prevalence, characteristics, and
      outcomes of asymptomatic left ventricular (LV) systolic dysfunction in patients
      with severe aortic stenosis (AS). BACKGROUND: Management of asymptomatic patients
      with severe AS remains controversial. In these patients, LV systolic dysfunction,
      defined in the guidelines as ejection fraction <50%, is a Class I(C) indication
      for aortic valve replacement (AVR), but its prevalence is unknown. METHODS: A
      retrospective study of adults >=40 years of age with severe valvular AS (peak
      velocity >=4 m/s, mean gradient >40 mm Hg, aortic valve area [AVA] <1 cm(2), or
      AVA index <0.6 cm(2)/m(2)) from 1984 to 2010 was undertaken. Patients with prior
      cardiac surgery, severe coronary artery disease, or greater than moderate aortic
      regurgitation were excluded. RESULTS: Of 9,940 patients with severe AS, 43 (0.4%)
      patients had asymptomatic LV dysfunction. Age was 73 +/- 14 years and 70% were
      male. Hypertension (78%) and LV hypertrophy (LV mass index 143 +/- 36 g/m(2))
      were characteristic. Fifty-three percent of these patients developed symptoms at
      21 +/- 19 months after diagnosis. During 7.5 +/- 6.7-year follow-up, 5-year
      mortality was 48%. After multivariable adjustment, there was no survival
      advantage with AVR in asymptomatic, severe AS with LV dysfunction (p = 0.51).
      CONCLUSIONS: In severe AS, the prevalence of asymptomatic LV systolic dysfunction
      is 0.4%. Despite an asymptomatic clinical status, patients with severe AS and LV
      ejection fraction <50% have a poor prognosis, with or without AVR.

PMID- 23122794
TI  - Recurrent ventricular tachycardia after catheter ablation in post-infarct
      cardiomyopathy: "failure" of ablation or progression of the substrate?

PMID- 23122795
TI  - Novel protein therapeutics for systolic heart failure: chronic subcutaneous B
      type natriuretic peptide.
AB  - OBJECTIVES: The purpose of the present study was to translate our laboratory
      investigations to establish safety and efficacy of 8 weeks of chronic SC B-type
      natriuretic peptide (BNP) administration in human Stage C heart failure (HF).
      BACKGROUND: B-Type natriuretic peptide is a cardiac hormone with vasodilating,
      natriuretic, renin-angiotensin inhibiting, and lusitropic properties. We have
      previously demonstrated that chronic cardiac hormone replacement with
      subcutaneous (SC) administration of BNP in experimental HF resulted in improved
      cardiovascular function. METHODS: We performed a randomized double-blind placebo
      controlled proof of concept study comparing 8 weeks of SC BNP (10 MUg/kg bid) (n
      = 20) with placebo (n = 20) in patients with ejection fraction <35% and New York
      Heart Association functional class II to III HF. Primary outcomes were left
      ventricular (LV) volumes and LV mass determined by cardiac magnetic resonance
      imaging. Secondary outcomes include LV filling pressure by Doppler echo, humoral
      function, and renal function. RESULTS: Eight weeks of chronic SC BNP resulted in
      a greater reduction of LV systolic and diastolic volume index and LV mass index
      as compared with placebo. There was a significantly greater improvement of
      Minnesota Living with Heart Failure score, LV filling pressure as demonstrated by
      the reductions of E/e' ratio, and decrease in left atrial volume index as
      compared with placebo. Glomerular filtration rate was preserved with SC BNP, as
      was the ability to activate plasma 3',5'-cyclic guanosine monophosphate (p < 0.05
      vs. placebo). CONCLUSIONS: In this pilot proof of concept study, chronic protein
      therapy with SC BNP improved LV remodeling, LV filling pressure, and Minnesota
      Living with Heart Failure score in patients with stable systolic HF on optimal
      therapy. Renin-angiotensin was suppressed, and glomerular filtration rate was
      preserved. Subcutaneous BNP represents a novel, safe, and efficacious protein
      therapeutic strategy in human HF. Further studies are warranted to determine
      whether these physiologic observations can be translated into improved clinical
      outcomes and ultimately delay the progression of HF. (Cardiac Hormone Replacement
      With BNP in Heart Failure: A Novel Therapeutic Strategy; NCT00252187).

PMID- 23122796
TI  - Reasons for recurrent ventricular tachycardia after catheter ablation of post
      infarction ventricular tachycardia.
AB  - OBJECTIVES: The purpose of this study was to assess the determinants of
      ventricular tachycardia (VT) recurrence in patients who underwent VT ablation for
      post-infarction VT. BACKGROUND: The factors that predict recurrence of VT after
      catheter ablation in patients with prior infarctions are not well described.
      METHODS: Catheter ablation was performed in 98 consecutive patients (88 males
      [90%]; mean age 67 +/- 10 years; ejection fraction 27 +/- 13%) with post
      infarction VT. Electrograms from the implantable cardioverter-defibrillator were
      analyzed, and VTs were classified as clinical, nonclinical, or new clinical.
      RESULTS: A total of 725 VTs were induced during the ablation procedure. All VTs
      were targeted. In 76 patients, 105 clinical VTs were inducible. Critical sites
      were identified with entrainment mapping and pace-mapping (>=10 of 12 matching
      leads) for 75 of 105 clinical VTs (71%) and for 278 of 620 nonclinical VTs (45%).
      Post-ablation, the clinical VT was not inducible in any patient, and all VTs were
      rendered noninducible in 63% of the patients. Over a mean follow-up period of 35
      +/- 23 months, 65 of 98 patients (66%) had no recurrent VTs and 33 (34%) had VT
      recurrence. A new VT occurred in 26 of 33 patients (79%), and a prior clinical VT
      recurred in 7 patients (21%). Patients with recurrent VT had a larger scar area
      as assessed by electroanatomic mapping compared with patients without recurrent
      VTs (93 +/- 40 cm(2) vs. 69 +/- 30 cm(2); p = 0.002). In patients with repeat
      procedures, the majority of inducible VTs for which a critical area could be
      identified were at a distance of 6 +/- 3 mm to the prior ablation lesions.
      CONCLUSIONS: Patients with recurrent VTs have a larger scar as assessed by
      electroanatomic mapping. Most recurrent VTs were new, and the majority of these
      VTs were mapped to the vicinity of prior ablation lesions in patients with repeat
      procedures.

PMID- 23122797
TI  - Prognostic value of coronary magnetic resonance angiography for prediction of
      cardiac events in patients with suspected coronary artery disease.
AB  - OBJECTIVES: This study sought to determine whether whole-heart coronary magnetic
      resonance angiography (CMRA) can predict cardiac events in patients with
      suspected coronary artery disease. BACKGROUND: Recent studies demonstrated that
      the presence of stenosis on coronary computed tomography angiography has a
      significant prognostic impact on the prediction of cardiac events. However, the
      prognostic value of whole-heart CMRA is unknown. METHODS: We studied 207 patients
      with suspected coronary artery disease who underwent non-contrast-enhanced free
      breathing whole-heart CMRA acquired with a 1.5-T MR system and 32-channel cardiac
      coils. The presence of significant coronary stenosis (>=50% diameter reduction)
      was visually determined on sliding thin- maximum intensity projection images.
      Follow-up information was obtained for occurrence of severe cardiac events
      (cardiac death, myocardial infarction, and unstable angina) and all cardiac
      events (additionally including revascularization>90 days after CMRA). RESULTS:
      During a median follow-up of 25 months, 10 cardiac events, of which 5 were
      severe, were observed in 84 patients with significant stenosis. Whereas, in 123
      patients without significant stenosis, only 1 cardiac event with no severe event
      was observed. Kaplan-Meier curves demonstrated a significant difference in event
      free survival between the 2 groups for severe events (annual event rate, 3.9% and
      0%, respectively; log-rank test, p = 0.003), as well as for all cardiac events
      (6.3% and 0.3%; p < 0.001). Cox regression analysis showed that presence of
      significant stenosis on CMRA was associated with a >20-fold hazard increase for
      all cardiac events (hazard ratio: 20.78; 95% confidence interval: 2.65 to 162.70;
      p = 0.001). CONCLUSIONS: Whole-heart CMRA is useful for predicting the future
      risk for cardiac events in patients with suspected coronary artery disease.

PMID- 23122798
TI  - Endovascular repair of ascending aortic dissection: a novel treatment option for
      patients judged unfit for direct surgical repair.
AB  - OBJECTIVES: This paper sought to report the outcomes of patients who are
      considered unfit for urgent surgical repair of ascending aortic dissections
      (AADs) who were treated using a novel endovascular repair strategy. BACKGROUND:
      AAD is best treated by direct surgical repair. Patients who are unable to undergo
      this form of treatment have poor prognoses. Previously, clinical case reports
      related to endovascular repair of AAD have been controversial. METHODS: Between
      May 2009 and January 2011, 41 consecutive patients with AAD were treated in our
      institution. Fifteen patients were considered poor candidates for direct surgical
      repair and subsequently underwent the endovascular repair. RESULTS: The nature of
      the referral process to our tertiary care facility made the median time from
      aortic dissection onset to treatment 25.5 days (range: 6 to 353 days).
      Dissections in 5 patients (33.3%) were considered acute, and those in 10 patients
      (66.7%) were considered chronic. The rate of successful stent-graft deployment
      was 100%, and there were no major morbidities or deaths in the perioperative
      period. Median follow-up was 26 months (range: 16 to 35 months). One new
      dissection occurred in the aortic arch at 3 months and was treated with a
      branched endograft. Significant enlargements of true lumens and decreases of
      false lumens and overall thoracic aorta were noted after the procedures.
      CONCLUSIONS: Endovascular repair of AAD was an appropriate treatment option in
      patients who were considered poor candidates for traditional direct surgical
      repair by the clinical criteria used in our institution. A larger series of cases
      with longer follow-up is needed to substantiate these results.

PMID- 23122800
TI  - Coronary magnetic resonance imaging: coming of age.

PMID- 23122799
TI  - Sex differences in arterial stiffness and ventricular-arterial interactions.
AB  - OBJECTIVES: This study sought to assess sex differences in ventricular-arterial
      interactions. BACKGROUND: Heart failure with preserved ejection fraction is more
      prevalent in women than in men, but the basis for this difference remains
      unclear. METHODS: Echocardiography and arterial tonometry were performed to
      quantify arterial and ventricular stiffening and interaction in 461 participants
      without heart failure (189 men, age 67 +/- 9 years; 272 women, age 65 +/- 10
      years). Aortic characteristic impedance (Z(c)), total arterial compliance
      (pulsatile load), and systemic vascular resistance index (steady load) were
      compared between men and women, and sex-specific multivariable regression
      analyses were performed to assess associations of these arterial parameters with
      diastolic dysfunction and ventricular-arterial coupling (effective arterial
      elastance/left ventricular end-systolic elastance [Ea/Ees]) after adjustment for
      potential confounders. RESULTS: Z(c) was higher and total arterial compliance was
      lower in women, whereas systemic vascular resistance index was similar between
      sexes. In women but not men, higher log Z(c) was associated with mitral inflow
      E/A ratio (beta +/- SE: -0.17 +/- 0.07), diastolic dysfunction (odds ratio: 7.8;
      95% confidence interval: 2.0 to 30.2) and Ea/Ees (beta +/- SE: 0.13 +/- 0.04) (p
      <= 0.01 for all). Similarly, total arterial compliance was associated with E/A
      ratio (beta +/- SE: 0.12 +/- 0.04), diastolic dysfunction (odds ratio: 0.33; 95%
      confidence interval: 0.12 to 0.89), and Ea/Ees (beta +/- SE: -0.09 +/- 0.03) in
      women only (p <= 0.03 for all). Systemic vascular resistance index was not
      associated with diastolic dysfunction or Ea/Ees. CONCLUSIONS: Proximal aortic
      stiffness (Z(c)) is greater in women than men, and women may be more susceptible
      to the deleterious effects of greater pulsatile and early arterial load on
      diastolic function and ventricular-arterial interaction. This may contribute to
      the greater risk of heart failure with preserved ejection fraction in women.

PMID- 23122801
TI  - Comparison of the prognosis of spontaneous and percutaneous coronary intervention
      related myocardial infarction.
AB  - OBJECTIVES: This study compared prognoses of myocardial infarction related to
      percutaneous coronary intervention (PCI, procedural MI) using increasing creatine
      kinase-myocardial band (CK-MB) thresholds with spontaneous MI. BACKGROUND:
      Procedural MI usually is defined by a CK-MB elevation of more than 3 times the
      upper limit of normal (ULN), but higher thresholds have been proposed. METHODS:
      Patients from the EARLY-ACS (Early Glycoprotein IIb/IIIa Inhibition in Non-ST
      Segment Elevation Acute Coronary Syndrome) study and the SYNERGY (Superior Yield
      of the New strategy of Enoxaparin, Revascularization and GlYcoprotein IIb/IIIa
      inhibitors) study treated with PCI were included. The primary end point was 1
      year all-cause mortality from 24 h after PCI. To determine an enzymatic threshold
      for procedural MI with a prognosis similar to that of spontaneous MI, we
      redefined procedural MI using increasing CK-MB thresholds and compared
      corresponding hazard ratios with those of spontaneous MI (CK-MB more than twice
      the ULN). Hazard ratios for mortality for procedural and spontaneous MI were
      calculated using Cox proportional hazards regression and Global Registry of Acute
      Cardiac Events covariates for risk adjustment. RESULTS: Nine thousand eighty
      seven patients who underwent PCI (46.8%) were included; 773 procedural MI and 239
      spontaneous MI occurred within 30 days. Adjusted hazard ratios for 1-year death
      were 1.39 (95% confidence interval [CI]: 1.01 to 1.89) for procedural MI and 5.37
      (95% CI: 3.90 to 7.38) for spontaneous MI. The CK-MB threshold for procedural MI
      that achieved the same prognosis as spontaneous MI was 27.7 times the ULN (95%
      CI: 13.9 to 58.4), but this differed between the SYNERGY study (57.9 times the
      ULN, 95% CI: 17.9 to 63.6) and the EARLY-ACS study (20.4 times the ULN, 95% CI:
      5.16 to 24.2). Of all procedural MI, 49 (6%) had CK-MB elevations of 27.7 or more
      times the ULN. CONCLUSIONS: The current enzymatic definition of procedural MI (CK
      MB more than 3 times the ULN) used in clinical trials is less strongly associated
      with death than that of spontaneous MI. Procedural MI achieves similar prognosis
      for 1-year mortality when much higher CK-MB thresholds are applied.

PMID- 23122802
TI  - Cost-effectiveness of transcatheter aortic valve replacement compared with
      surgical aortic valve replacement in high-risk patients with severe aortic
      stenosis: results of the PARTNER (Placement of Aortic Transcatheter Valves) trial
      (Cohort A).
AB  - OBJECTIVES: The aim of this study was to evaluate the cost-effectiveness of
      transcatheter aortic valve replacement (TAVR) compared with surgical aortic valve
      replacement (AVR) for patients with severe aortic stenosis and high surgical
      risk. BACKGROUND: TAVR is an alternative to AVR for patients with severe aortic
      stenosis and high surgical risk. METHODS: We performed a formal economic analysis
      based on cost, quality of life, and survival data collected in the PARTNER A
      (Placement of Aortic Transcatheter Valves) trial in which patients with severe
      aortic stenosis and high surgical risk were randomized to TAVR or AVR. Cumulative
      12-month costs (assessed from a U.S. societal perspective) and quality-adjusted
      life-years (QALYs) were compared separately for the transfemoral (TF) and
      transapical (TA) cohorts. RESULTS: Although 12-month costs and QALYs were similar
      for TAVR and AVR in the overall population, there were important differences when
      results were stratified by access site. In the TF cohort, total 12-month costs
      were slightly lower with TAVR and QALYs were slightly higher such that TF-TAVR
      was economically dominant compared with AVR in the base case and economically
      attractive (incremental cost-effectiveness ratio <$50,000/QALY) in 70.9% of
      bootstrap replicates. In the TA cohort, 12-month costs remained substantially
      higher with TAVR, whereas QALYs tended to be lower such that TA-TAVR was
      economically dominated by AVR in the base case and economically attractive in
      only 7.1% of replicates. CONCLUSIONS: In the PARTNER trial, TAVR was an
      economically attractive strategy compared with AVR for patients suitable for TF
      access. Future studies are necessary to determine whether improved experience and
      outcomes with TA-TAVR can improve its cost-effectiveness relative to AVR.

PMID- 23122803
TI  - Fluorescent oxygen sensitive microbead incorporation for measuring oxygen tension
      in cell aggregates.
AB  - Molecular oxygen is a main regulator of various cell functions. Imaging methods
      designed as screening tools for fast, in situ, 3D and non-interfering measurement
      of oxygen tension in the cellular microenvironment would serve great purpose in
      identifying and monitoring this vital and pivotal signalling molecule. We
      describe the use of dual luminophore oxygen sensitive microbeads to measure
      absolute oxygen concentrations in cellular aggregates. Stable microbead
      integration, a prerequisite for their practical application, was ensured by a
      site-specific delivery method that is based on the interactions between
      streptavidin and biotin. The spatial stability introduced by this method allowed
      for long term measurements of oxygen tension without interfering with the cell
      aggregation process. By making multiple calibration experiments we further
      demonstrated the potential of these sensors to measure local oxygen tension in
      optically dense cellular environments.

PMID- 23122804
TI  - Intrinsically active nanobody-modified polymeric micelles for tumor-targeted
      combination therapy.
AB  - Various different passively and actively targeted nanomedicines have been
      designed and evaluated over the years, in particular for the treatment of cancer.
      Reasoning that the potential of ligand-modified nanomedicines can be
      substantially improved if intrinsically active targeting moieties are used, we
      have here set out to assess the in vivo efficacy of nanobody-modified core
      crosslinked polymeric micelles containing covalently entrapped doxorubicin.
      Nanobody-modified polymeric micelles were found to inhibit tumor growth even in
      the absence of a drug, and nanobody-modified micelles containing doxorubicin were
      significantly more effective than nanobody-free micelles containing doxorubicin.
      Based on these findings, we propose that the combination of two therapeutic
      strategies within one nanomedicine formulation, i.e. the intrinsic
      pharmacological activity of ligand-modified carrier materials with the cytostatic
      activity of the incorporated chemotherapeutic agents, is a highly promising
      approach for improving the efficacy of tumor-targeted combination therapy.

PMID- 23122805
TI  - Swiss and Dutch "consumer-driven health care": ideal model or reality?
AB  - This article addresses three topics. First, it reports on the international
      interest in the health care reforms of Switzerland and The Netherlands in the
      1990s and early 2000s that operate under the label "managed competition" or
      "consumer-driven health care." Second, the article reviews the behavior
      assumptions that make plausible the case for the model of "managed competition."
      Third, it analyze the actual reform experience of Switzerland and Holland to
      assess to what extent they confirm the validity of those assumptions. The article
      concludes that there is a triple gap in understanding of those topics: a gap
      between the theoretical model of managed competition and the reforms as
      implemented in both Switzerland and The Netherlands; second, a gap between the
      expectations of policy-makers and the results of the reforms, and third, a gap
      between reform outcomes and the observations of external commentators that have
      embraced the reforms as the ultimate success of "consumer-driven health care."
      The article concludes with a discussion of the implications of this "triple gap".

PMID- 23122807
TI  - Aberrant hypomethylation of SALL4 gene in patients with myelodysplastic syndrome.
AB  - The abnormalities of SALL4 gene, which encodes a zinc-finger transcription factor
      and is essential for developmental events, have been found to be involved in
      tumorigenesis. In this study, we investigated the methylation status of the CpG
      island of SALL4 promoter region in myelodysplastic syndrome (MDS) using
      methylation-specific PCR (MSP). Aberrant hypomethylation of SALL4 gene was found
      in 21.7% (18/83) of the cases analyzed. A significantly positive correlation was
      identified between the level of SALL4 transcript and the status of SALL4
      hypomethylation (R=0.641, P<0.001). No correlation was found between SALL4
      hypomethylation and clinical parameters. However, the frequency of SALL4
      hypomethylation significantly increased in higher risk MDS (14% in Low/Int-1
      versus 39% in Int-2/High, P=0.031). The association between SALL4 hypomethylation
      and the mutations in three methylation modifiers (IDH1, IDH2 and DNMT3A) was not
      observed. Although the estimated 50% survival time of the SALL4-hypomethylated
      group was shorter than that of SALL4-methylated group (11.0 months vs. 20.0
      months), the difference was not statistically significant (P=0.430). These
      findings suggest that hypomethylation of SALL4 promoter is a common event in MDS.

PMID- 23122806
TI  - Validation and proposals for a refinement of the WHO 2008 classification of
      myelodysplastic syndromes without excess of blasts.
AB  - In 2008, the WHO proposed changes in the classification of MDS regarding RCUD and
      MDS unclassifiable. We validated these proposals by using 2032 patients of the
      Dusseldorf MDS Registry. 10% of the patients had RCUD and 6% MDS-U. Among
      patients with RCUD, only 9% had RN and 6% had RT. There was no correlation
      between dysplastic cell line and type of cytopenia. There was no difference in
      prognosis between RCMD and MDS-U and between RA, RT, and RN. The separation of
      RA, RN, and RT is not justified suggesting a consolidation as RCUD. MDS-U should
      be integrated into RCMD.

PMID- 23122808
TI  - Relevance of feline interferon omega for clinical improvement and reduction of
      concurrent viral excretion in retrovirus infected cats from a rescue shelter.
AB  - Feline Immnunodeficiency (FIV) and Feline Leukemia (FeLV) viruses are common
      infectious agents in stray cats and shelter environments. Recombinant feline
      interferon-omega (rFeIFNomega) has shown an antiviral action not only against FIV
      and FeLV but also against herpesvirus (FHV-1) and calicivirus (FCV). Sixteen
      naturally infected FIV/FeLV cats were followed during rFeIFNomega therapy in
      order to monitor clinical signs and to correlate with excretion of concomitant
      viruses (FCV, FHV-1, feline coronavirus (FCoV) and parvovirus (FPV)). Cats were
      submitted to clinical evaluations and concomitant virus excretion assessement.
      Comparing D0-D65, 10/16 cats improved clinical scores. Of the 10 cats positive
      for FHV-1 on D0, 4 were negative and 6 reduced viral loads. Of the 11 FCoV
      positive cats, 9 reduced viral loads. The 13 FCV positive cats and the FPV
      positive cat were negative on D65. In conclusion, rFeIFNomega improves clinical
      signs and reduces concurrent viral excretion in naturally infected retroviral
      cats.

PMID- 23122809
TI  - Mycobacterium avium subsp. paratuberculosis invades through M cells and
      enterocytes across ileal and jejunal mucosa of lambs.
AB  - Mechanism of Mycobacterium avium subsp. paratuberculosis (Map) invasion through
      intestinal mucosa is not completely understood. In the present study, we
      developed an in vivo multiple-intestinal loop model in lambs to investigate (i)
      the type of cells involved in the bacterial uptake across the intestinal mucosa,
      (ii) the efficiency of bacterial uptake in different segments of the small
      intestine and (iii) the ability of different strains of Map to invade the various
      segments of the small intestine. Four loops on ileum and four loops each on
      Peyer's patch and non-Peyer's patch areas of jejunum were constructed by surgical
      procedure. The caprine, bovine, and vaccine strains of Map were used for
      infection. Map-infected intestinal loop tissues were collected at 1, 3, 6, 12,
      and 24 h post-infection and processed for electron microscopy, histology,
      bacterial culture and bacterial counting. All these parameters revealed that Map
      invaded through M cells and the enterocytes and bacterial translocation across M
      cells was greater than the enterocytes. Bacterial invasion was greater in ileal
      loops when compared to jejunal loops. Within the jejunal loops, bacterial uptake
      was higher in Peyer's patch areas than that of non-Peyer's patch areas. The
      caprine and bovine strains of Map showed greater ability for invasion into the
      small intestinal mucosa than that of the vaccine strain.

PMID- 23122810
TI  - Expression of platelet derived growth factor beta receptor, its activation and
      downstream signals in bovine cutaneous fibropapillomas.
AB  - Bovine cutaneous fibropapillomas are benign skin tumours formed by proliferation
      of epidermal keratinocytes and dermal fibroblasts caused by bovine
      papillomaviruses (BPVs). BPV E5 oncoprotein plays a key role in neoplastic cell
      transformation by specifically binding to the platelet derived growth factor beta
      receptor (PDGFbetaR) causing its phosphorylation and activation of proliferation
      and survival signal transduction pathways, among these phosphatidyl inositol-3
      kinase (PI3K)/Akt and Ras-mitogen-activated-protein-kinase-Erk (Ras-MAPK-Erk)
      pathways. The aim of this study was to investigate the expression of PDGFbetaR,
      its phosphorylation status and expression of the downstream molecules phospho-Akt
      (pAkt) and phospho-Erk (pErk), in naturally occurring bovine cutaneous
      fibropapillomas. By immunohistochemistry on serial sections we showed cytoplasmic
      co-expression of the PDGFbetaR and E5 protein in neoplastic tissue. Western blot
      analysis revealed that PDGFbetaR was phosphorylated in higher amount in tumour
      samples compared to normal skin. pAkt, but not pErk, was also overexpressed in
      tumour samples. These findings may provide new insights into the aetiopathogenic
      mechanisms underlying naturally occurring bovine fibropapillomas and contribute
      to understanding the molecular scenario underlying BPV induced tumourigenesis.

PMID- 23122811
TI  - Lidocaine serum concentration after epidural administration in combination with
      morphine and fentanyl in rabbit--a preliminary study.
AB  - Morphine and fentanyl are often used as adjuvants in epidural anesthesia to
      prolong analgesia. The aim of this study was to evaluate the impact of addition
      of morphine or fentanyl to lidocaine on serum lidocaine concentrations in rabbits
      after epidural administration. During general anesthesia, rabbits of the group L
      received epidurally 2% lidocaine, rabbits of the group LM 2% lidocaine and
      morphine, and rabbits of the group LF 2% lidocaine and fentanyl. Blood for
      determination of serum lidocaine concentration was taken before anesthesia and in
      first 90 min after epidural administration. After 5, 10, and 25 min in the group
      L the lidocaine serum concentrations were the lowest, while in the group LM the
      lidocaine serum concentrations were the highest. Morphine and fentanyl did not
      cause significant changes of serum lidocaine concentration in rabbits and may be
      used as adjuvant in epidural anesthesia without significant increase in lidocaine
      absorption from epidural space.

PMID- 23122812
TI  - Is cystathionine gamma-lyase protein expressed in the heart?
AB  - Hydrogen sulfide (H(2)S) has emerged as an important gasotransmitter, offering
      protection against ischemia-reperfusion damage to the heart. Cystathionine gamma
      lyase (CSE) is believed to be the major H(2)S-generating enzyme in the heart.
      Quite contrary to the general contemplation, CSE protein in cardiac tissues has
      not been convincingly detected and it has become an issue of controversy. In the
      present study, we isolated cardiac tissues from wild type (WT) and CSE knockout
      mice or the rat. CSE expression at transcriptional and translational levels were
      assayed by RT-PCR and Western Blotting with five different antibodies (four
      commercial products and one homemade), respectively. Cardiac H(2)S production
      rate was also examined. Our data validated the expression of CSE mRNA in the
      heart of WT mice or rats, not in CSE KO mice. Using all 5 different anti-CSE
      antibodies, we could not detect CSE proteins in mouse or rat cardiac tissues or
      in cultured rat cardiomyocytes. On the other hand, CSE protein was detectable in
      liver tissues from WT mice with the expected molecular mass of 43.6 kDa. H(2)S
      production rate of heart tissues in CSE KO mice was significantly decreased
      compared with that in WT mice. In the presence of an CSE inhibitor, D,L
      propargylglycine, H(2)S production rate of heart tissues from WT mice was
      inhibited by approximately 80%. It appears that CSE mediates mostly endogenous
      H(2)S production in heart tissues. However, the available anti-CSE antibodies
      could not detect CSE proteins in rat and mouse heart tissues or rat
      cardiomyocytes.

PMID- 23122813
TI  - Hypothermia-dependent and -independent effects of forced swim on the
      phosphorylation states of signaling molecules in mouse hippocampus.
AB  - Forced swim (FS) stress induces diverse biochemical responses in the brain of
      rodents. Here, we examined the effect of hypothermia induced by FS in cold water
      on the phosphorylation of FS-sensitive signaling molecules in the mouse brain. As
      we have shown previously, FS in cold water induced a significant increase in the
      level of tyrosine phosphorylation of SIRPalpha, a neuronal membrane protein, in
      mouse hippocampus, while such effect of FS was markedly reduced in mice subjected
      to FS in warm water. FS in cold water also induced phosphorylation of mitogen
      activated protein kinase kinase (MEK) as well as of cAMP response element-binding
      protein (CREB), or dephosphorylation of alpha isoform of Ca(2+)/calmodulin
      dependent protein kinase II (alphaCaMKII) in the hippocampus. These effects of FS
      on the phosphorylation of these molecules were also lost in mice subjected to FS
      in warm water. Genetic ablation of SIRPalpha did not change the phosphorylation
      states of these molecules in the brain. Forced cooling of anesthetized mice,
      which induced a marked increase in the phosphorylation of SIRPalpha, induced
      dephosphorylation of alphaCaMKII in the brain, while the same treatment did not
      affect the phosphorylation level of MEK and CREB. Hibernation also induced an
      increase and a decrease of the phosphorylation of SIRPalpha and alphaCaMKII,
      respectively, in the brain of chipmunk. These results suggest that hypothermia is
      a major element that determines the levels of phosphorylation of alphaCaMKII and
      SIRPalpha during the FS in cold water, while it is not for the phosphorylation
      levels of MEK and CREB.

PMID- 23122815
TI  - Suicides by fire in South Korea.

PMID- 23122814
TI  - Impairment of interferon regulatory factor-3 activation by hepatitis C virus core
      protein basic amino acid region 1.
AB  - Interferon regulatory factor-3 (IRF-3), a key transcriptional factor in the type
      I interferon system, is frequently impaired by hepatitis C virus (HCV), in order
      to establish persistent infection. However, the exact mechanism by which the
      virus establishes persistent infection has not been fully understood yet. The
      present study aimed to investigate the effects of various HCV proteins on IRF-3
      activation, and elucidate the underlying mechanisms. To achieve this, full-length
      HCV and HCV subgenomic constructs corresponding to structural and each of the
      nonstructural proteins were transiently transfected into HepG2 cells. IFN-beta
      induction, plaque formation, and IRF-3 dimerization were elicited by Newcastle
      disease virus (NDV) infection. The expressions of IRF-3 homodimer and its
      monomer, Ser386-phosphorylated IRF-3, and HCV core protein were detected by
      immunofluorescence and western blotting. IFN-beta mRNA expression was quantified
      by real-time PCR (RT-PCR), and IRF-3 activity was measured by the levels of IRF-3
      dimerization and phosphorylation, induced by NDV infection or
      polyriboinosinic:polyribocytidylic acid [poly(I:C)]. Switching of the expression
      of the complete HCV genome as well as the core proteins, E1, E2, and NS2,
      suppressed IFN-beta mRNA levels and IRF-3 dimerization, induced by NDV infection.
      Our study revealed a crucial region of the HCV core protein, basic amino acid
      region 1 (BR1), to inhibit IRF-3 dimerization as well as its phosphorylation
      induced by NDV infection and poly (I:C), thus interfering with IRF-3 activation.
      Therefore, our study suggests that rescue of the IRF-3 pathway impairment may be
      an effective treatment for HCV infection.

PMID- 23122816
TI  - Design and evaluation of azaindole-substituted N-hydroxypyridones as glyoxalase I
      inhibitors.
AB  - We conducted a high throughput screening for glyoxalase I (GLO1) inhibitors and
      identified 4,6-diphenyl-N-hydroxypyridone as a lead compound. Using a binding
      model of the lead and public X-ray coordinates of GLO1 enzymes complexed with
      glutathione analogues, we designed 4-(7-azaindole)-substituted 6-phenyl-N
      hydroxypyridones. 7-Azaindole's 7-nitrogen was expected to interact with a water
      network, resulting in an interaction with the protein. We validated this
      inhibitor design by comparing its structure-activity relationship (SAR) with that
      of corresponding indole derivatives, by analyzing the binding mode with X-ray
      crystallography and by evaluating its thermodynamic binding parameters.

PMID- 23122817
TI  - 1-(3,4,5-Trimethoxyphenyl)ethane-1,2-diyl esters, a novel compound class with
      potent chemoreversal activity.
AB  - 1-(3,4,5-Trimethoxyphenyl)ethane-1,2-diyl esters, which share a fragment from (+/
      )-3'-O-4'-O-bis(3,4-dimethoxycinnamoyl)-cis-khellactone (DMDCK) and 3'R,4'R
      disubstituted-2',2'-dimethyldihydropyrano[2,3-f]chromone (DSP), exhibited
      remarkable chemoreversal activity on multidrug resistant human nasopharyngeal
      carcinoma (KB) when combined with three anticancer drugs, paclitaxel, vincristine
      and doxorubicin. Among 15 novel synthesized analogs, bis-trimethoxybenzoyl
      derivative 15 was the most active (340-fold more active than verapamil when used
      with vincristine) followed by two di-cinnamoyl derivatives, 10 and 11, and then
      di-cyclohexanecarbonyl derivative 9. All aliphatic chain derivatives, 3-5, showed
      no activity. Structure-activity relationship study indicated that a di-ester
      structure was critical to enhance the activity resulting from the maintenance of
      the spatial arrangement proposed by the pharmacophore based on the verapamil
      binding site. Further mechanism of action study showed 15 inhibited mainly P
      glycoprotein efflux pump function, while 13 exhibited an additional multidrug
      resistance-associated protein efflux pump function.

PMID- 23122818
TI  - Synthesis and biological evaluation of a water-soluble derivative of the potent V
      ATPase inhibitor archazolid.
AB  - The water-solubility of the highly potent V-ATPase inhibitors archazolid A and
      the glucosylated derivative archazolid C was studied in the presence of a wide
      range of cosolvents, revealing very low solubilites. The first water-soluble
      analogue was then designed, synthesized, and evaluated for V-ATPase inhibitory
      activity in vitro.

PMID- 23122819
TI  - Azo-reductase activated budesodine prodrugs for colon targeting.
AB  - Budesodine is a synthetic glurocorticoid that undergoes substantial first pass
      metabolism, limiting systemic exposure. Its use in treatment of inflammatory
      bowel disease would benefit from a targeting strategy that could lead to a local
      topical effect, improving safety and increasing anti-inflammatory efficacy. A two
      step prodrug strategy involving azoreduction/cyclization that we developed
      previously for prednisolone is here applied with some variations to budesonide.
      The budesodine prodrugs were tested using an in vitro azoreductase assay
      simulating human colonic microflora. The kinetics of amino steroid ester
      cyclization and its pH dependence was also evaluated. The stability of the
      prodrugs systems in simulated human duodenal and gastric fluid was evaluated to
      determine the likelihood of intact intestinal transit. The propionic acid derived
      prodrug 3 undergoes rapid activation by Clostridium perfingens and its putative
      reduction product cyclizes with acceptable rapidity when synthesized
      independently. These properties of 3 suggest that it has potential in management
      of ulcerative colitis.

PMID- 23122820
TI  - Inhibition of HIV-1 capsid assembly: optimization of the antiviral potency by
      site selective modifications at N1, C2 and C16 of a 5-(5-furan-2-yl-pyrazol-1-yl)
      1H-benzimidazole scaffold.
AB  - A uHTS campaign led to the discovery of a 5-(5-furan-2-ylpyrazol-1-yl)-1H
      benzimidazole series that inhibits assembly of HIV-1 capsid. Synthetic
      manipulations at N1, C2 and C16 positions improved the antiviral potency by a .
      The X-ray structure of 33 complexed with the capsid N-terminal domain allowed
      identification of major interactions between the inhibitor and the protein.

PMID- 23122821
TI  - Design and discovery of new (3S,5R)-5-[4-(2-chlorophenyl)-2,2-dimethyl-5
      oxopiperazin-1-yl]piperidine-3-carboxamides as potent renin inhibitors.
AB  - Utilizing X-ray crystal structure analysis, (3S,5R)-5-[4-(2-chlorophenyl)-2,2
      dimethyl-5-oxopiperazin-1-yl]piperidine-3-carboxamides were designed and
      identified as renin inhibitors. The most potent compound 15 demonstrated
      favorable pharmacokinetic and pharmacodynamic profiles in rat.

PMID- 23122822
TI  - Structure requirements for anaerobe processing of azo compounds: implications for
      prodrug design.
AB  - This Letter generalizes the metabolism of the azo class of compounds by
      Clostridium perfringens, an anaerobe found in the human colon. A recently
      reported 5-aminosalicylic acid-based prednisolone prodrug was shown to release
      the drug when incubated with the bacteria, while the para-aminobenzoic acid
      (PABA) based analogue did not. Instead, it showed a new HPLC peak with a
      relatively close retention time to the parent which was identified by LCMS as the
      partially reduced hydrazine product. This Letter investigates azoreduction across
      a panel of substrates with varying degrees of electronic and steric similarity to
      the PABA-based compound. Azo compounds with an electron donating group on the azo
      containing aromatic ring showed immediate disproportionation to their parent
      amines without any detection of hydrazine intermediates by HPLC. Compounds
      containing only electron withdrawing groups are partially and reversibly reduced
      to produce a stable detectable hydrazine. They do not disproportionate to their
      parent amines, but regenerate the parent azo compound. This incomplete reduction
      is relevant to the design of azo-based prodrugs and the toxicology of azo-based
      dyes.

PMID- 23122823
TI  - Selection of a screening panel of rhinoviral serotypes.
AB  - A novel methodology for the selection of a representative primary and secondary
      screening panel of rhinoviral serotypes for the purposes of identifying potential
      antiviral agents is presented. This methodology focuses on the active-sites of
      the rhinoviral proteins but does not invoke historical SAR data, thereby avoiding
      compound bias.

PMID- 23122824
TI  - Prognostic role of MMP-9 expression in head and neck carcinoma patients treated
      with radiotherapy or chemoradiotherapy.
AB  - OBJECTIVES: The purpose of this study was to evaluate the prognostic significance
      of the expression of metalloproteinases (MMPs)-2 and -9 at a transcriptional
      level in patients with head and neck squamous cell carcinoma (HNSCC). PATIENTS
      AND METHODS: Real-time polymerase chain reaction was used to determine mRNA
      expression levels of MMP-2 and MMP-9 in 105 consecutive patients with HNSCC
      treated with radiotherapy or chemoradiotherapy. Continuous values of mRNA
      expression levels were analyzed using a classification and regression tree (CART)
      method. RESULTS: Patients were grouped into two categories according to the
      results from CART analysis; high (n=71) and low (n=34) expression levels of MMP
      9. MMP-2 expression was not included in the model. The 5-year adjusted survival
      rate was 92.9% for patients with low MMP-9 expression level and 61.0% for
      patients with a high expression level (P=0.006). Overexpression of MMP-9 was
      associated with a decrease in local control of the disease. In a multivariate
      analysis, MMP-9 expression was the only variable that was associated with
      adjusted survival. Considering patients with a low MMP-9 expression level as the
      reference group, patients with a high MMP-9 expression level had a 6.1 times
      higher risk of death from HNSCC (CI 95%: 1.4-26.4). CONCLUSION: We found a
      significant relationship between the transcription of MMP-9 and adjusted survival
      in HNSCC patients treated with radiotherapy or chemoradiotherapy. These results
      suggest that MMP-9 transcription may serve as a marker of treatment response to
      radiotherapy or chemo-radiotherapy in patients with HNSCC.

PMID- 23122825
TI  - Markedly elevated soluble E-cadherin in plasma of patient with pelvic
      inflammatory disease.
AB  - OBJECTIVE: To estimate the expression of plasma soluble E-cadherin and the gene
      polymorphism in patients with pelvic inflammatory disease (PID). DESIGN: Hospital
      based case-control study. SETTING: University hospital. PATIENT(S): Sixty-four
      women with PID. INTERVENTION(S): Blood specimen collection from patients before
      and after they received treatment. MAIN OUTCOME MEASURE(S): Enzyme-linked
      immunosorbent assay and polymerase chain reaction-restriction fragment length
      polymorphism were respectively used to measure the plasma soluble E-cadherin
      level and E-cadherin polymorphism. RESULT(S): The level of plasma E-cadherin was
      significantly elevated in patients with PID as compared with that in normal
      controls; it decreased significantly after treatment when compared with levels
      noted in the same patients before they received treatment. When the cutoff level
      of plasma E-cadherin level was set to 20.22 ng/mL on the basis of receiver
      operating characteristic curve (ROC), the sensitivity, specificity, and the area
      under the curve of plasma E-cadherin level for predicting PID were 0.81, 0.80,
      and 0.835 (95% confidence interval 0.76-0.90), respectively. The adjusted odds
      ratio for age, white blood cell count, and C-reactive protein levels was 19.66
      (5.48-70.47). CONCLUSION(S): Elevated plasma soluble E-cadherin expression was
      involved in the pathogenesis of PID and is useful for the diagnosis of PID.

PMID- 23122826
TI  - Role of decreased androgens in the ovarian response to stimulation in older
      women.
AB  - Ovarian testosterone increases the response of antral follicles to stimulation,
      declines with age, and has effects mediated or potentiated by insulin-like growth
      hormone I (IGF-I). Increased circulating insulin and IGF-I, exogenous
      testosterone, and increased local ovarian testosterone concentrations due to
      aromatase inhibition or exogenous luteinizing hormone/human chorionic
      gonadotropin are all associated with an increased ovarian response to
      gonadotropins. These factors should be further investigated alone or in
      combination for enhancing oocyte yield with fertility treatments, particularly in
      older reproductive-age women.

PMID- 23122828
TI  - The significance of insulin-like factor 3 as a marker of intratesticular
      testosterone.

PMID- 23122827
TI  - Effect of bilateral oophorectomy on adrenocortical function in women with
      polycystic ovary syndrome.
AB  - OBJECTIVE: To determine the impact of ovary-secreted products on adrenocortical
      function in women with PCOS by studying the adrenocortical response to acute
      adrenocorticotropic-stimulating hormone (ACTH) stimulation before and after
      bilateral oophorectomy. DESIGN: Prospective study. SETTING: Tertiary care medical
      center. PATIENT(S): Fourteen women with PCOS, scheduled for bilateral
      oophorectomy for benign indications, on postoperative transdermal estradiol
      (E(2)). INTERVENTION(S): Physical examination, blood sampling before and after
      oophorectomy, measurement of hormone levels; assessment of basal (Steroid(0)),
      maximum stimulated (Steroid(60)), and net increment (DeltaSteroid) levels of
      androstenedione (A4), dehydroepiandrosterone (DHEA), and cortisol (F) before and
      after ACTH 1-24 stimulation. MAIN OUTCOME MEASURE(S): Preoperative and
      postoperative basal and ACTH (1-24) stimulated hormone levels. RESULT(S): Total
      testosterone, free testosterone, and estrone levels decreased, and follicle
      stimulating hormone levels statistically significantly increased after
      oophorectomy. No statistically significant differences in E(2), DHEA sulfate
      (DHEAS), or sex hormone-binding globulin levels were detected. Basal and ACTH
      stimulated A4 levels statistically significantly decreased after oophorectomy,
      and DeltaA4 was statistically significantly increased. No statistically
      significant differences in DHEA(0), DHEA(60), or F(0) levels were detected. The
      F(60) and DeltaF levels tended to increase after oophorectomy, but the
      differences did not reach statistical significance. CONCLUSION(S): Ovarian
      factors do not appear to contribute significantly to the adrenocortical
      dysfunction of PCOS.

PMID- 23122829
TI  - Metformin decreases serum 8-hydroxy-2'-deoxyguanosine levels in polycystic ovary
      syndrome.
AB  - OBJECTIVE: To learn whether metformin treatment affects oxidative stress as
      measured by serum concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG). DESIGN:
      Double-blind, randomized, placebo-controlled trial. SETTING: University
      outpatient clinic. PATIENT(S): The study cohort consisted of 50 obese women (body
      mass index [BMI] >= 27 kg/m(2)) and 60 nonobese patients (BMI <27 kg/m(2)), mean
      age was 27.7 +/- 4.0 SD years. INTERVENTION(S): Randomization to receive
      metformin or placebo for 3 months. MAIN OUTCOME MEASURE(S): Serum levels of 8
      OHdG before and after medical treatment. RESULT(S): The levels of 8-OHdG were
      equal at baseline in the placebo and metformin groups. Obese women had higher
      baseline serum concentrations of 8-OHdG. Levels of 8-OHdG were statistically
      significantly reduced with metformin treatment, especially in obese patients with
      polycystic ovary syndrome. This study was a secondary subanalysis of a previously
      conducted prospective multicenter, randomized, placebo-controlled study on the
      effects of metformin on miscarriage, pregnancy, and miscarriage rates.
      CONCLUSION(S): Metformin treatment, compared with placebo, statistically
      significantly decreased 8-OHdG levels in women with polycystic ovary syndrome.
      CLINICAL TRIAL REGISTRATION NUMBER: NCT00994812.

PMID- 23122830
TI  - Overweight men with nonobstructive azoospermia have worse pregnancy outcomes
      after microdissection testicular sperm extraction.
AB  - OBJECTIVE: To evaluate the effect of obesity on the outcome of testicular sperm
      extraction (TESE) and assisted reproductive technology. DESIGN: Clinical
      retrospective study. SETTING: Center for reproductive medicine at a tertiary-care
      university hospital. PATIENT(S): Nine hundred seventy patients with
      nonobstructive azoospermia. INTERVENTION(S): Microdissection TESE followed by
      intracytoplasmic sperm injection (ICSI). MAIN OUTCOME MEASURE(S): Sperm retrieval
      rate and clinical pregnancy rate. RESULT(S): Testicular sperm were successfully
      retrieved in 55% of men overall. Of those with sperm found, clinical pregnancy
      rate was 51% and live birth rate 40%. Sperm retrieval rates were similar in men
      with body mass index (BMI) <25 kg/m(2), 25-30 kg/m(2), and >30 kg/m(2) (59%, 57%,
      and 54%, respectively). Mean BMI of men who contributed to pregnancy (27.3 +/-
      4.9 kg/m(2)) was lower than for men whose sperm did not contribute to a pregnancy
      (28.2 +/- 5.4 kg/m(2)). No man with BMI >43 kg/m(2) (n = 11) contributed to a
      successful pregnancy, even though sperm were found in men with BMI up to 57
      kg/m(2). On multivariable logistic regression analysis, male BMI was the only
      predictor of successful pregnancy among the variables analyzed, including male
      age, female age, and female BMI. CONCLUSION(S): Overweight men have lower
      clinical pregnancy rate after microdissection TESE and ICSI compared with men
      with normal BMI. Men with BMI >43 kg/m(2) did not contribute to any pregnancies,
      despite successful sperm retrieval.

PMID- 23122831
TI  - New target profiling for gastrointestinal disorders: where are we going?

PMID- 23122832
TI  - Umbilical hernias and cirrhose.
AB  - Umbilical hernia (UH) is the most frequent abdominal wall complication of ascites
      in cirrhotic patients. Treatment to control ascites, which mainly consists of
      repeated paracentesis or transjugular intrahepatic portosystemic shunt (TIPS), is
      mandatory; otherwise the risk of hernia recurrence is very high. Nowadays,
      surgical portosystemic shunts are rarely performed. Classically, hernia repair
      was offered only to patients with symptomatic UH, but presently, even if the
      hernia is minimally symptomatic, there is tendency to perform elective repair to
      avoid emergency surgery for complications associated with very high mortality and
      morbidity rates (rupture and strangulation). If liver transplantation is
      indicated, treatment of UH can be performed simultaneously, unless the hernia is
      highly symptomatic or complicated or if the waiting time on the transplantation
      list is long. During repair, necrotic skin tissue should be excised; the use of
      prosthetic material (if the defect is large) is possible with a low risk of
      infection as long as ascites is sterile. The advantage of laparoscopic repair of
      large UH is to avoid any skin incision (precluding ascitic fluid leak) and avoid
      exposing prosthetic mesh to necrotic infected tissue. If the defect is small, UH
      repair can be performed under local anesthesia.

PMID- 23122833
TI  - Parastomal hernia.
AB  - Despite advances in surgery including new prosthetic materials and the advent of
      laparoscopy, the treatment of parastomal hernias remains a challenge for the
      surgeon. This is mainly due to the very high recurrence rate. Adequate management
      requires preoperative multidisciplinary consultation to offer the most
      appropriate surgical solution to each patient. We propose a review of current
      knowledge about this complication.

PMID- 23122834
TI  - Off-clamp robot-assisted partial nephrectomy preserves renal function: a multi
      institutional propensity score analysis.
AB  - BACKGROUND: Ongoing efforts are focused on minimizing or eliminating renal
      ischemia during robot-assisted partial nephrectomy (RPN). Although various
      techniques allowing the elimination of renal hilar clamping have been described,
      large multi-institutional studies assessing perioperative and functional outcomes
      of this approach are lacking. OBJECTIVE: To evaluate perioperative and functional
      outcomes of RPN without hilar clamping and to assess comparative effectiveness
      relative to clamped RPN. DESIGN, SETTING, AND PARTICIPANTS: A multi-institutional
      data analysis of prospectively collected records of 886 RPNs performed by high
      volume surgeons across five academic institutions between 2007 and 2011 was
      carried out. A total of 66 patients who underwent RPN without hilar clamping were
      identified. After the exclusion of 17 patients, perioperative results of 49
      patients were compared against propensity score matched clamped controls.
      INTERVENTION: RPN without hilar clamping. OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: Descriptive statistics and propensity score matching. RESULTS AND
      LIMITATIONS: Patients undergoing off-clamp RPN had a mean tumor size of 2.5 cm
      (standard deviation [SD]: +/- 2.1) and a mean RENAL nephrometry score of 5.3 (SD:
      +/- 1.5). The mean preoperative estimated glomerular filtration rate (eGFR) was
      81 (SD: +/- 29). The mean estimated blood loss (EBL) was 210 ml (SD: +/- 212),
      and the mean operative time was 155 min (SD: +/- 46). No Clavien 3-5
      complications were recorded. The mean postoperative change in eGFR was 3% at
      first follow-up (1-3 mo), and no patient required postoperative dialysis. The
      positive surgical margin rate was 3% (n=2), with no disease recurrence reported
      at a mean follow-up of 21 mo. In propensity score matched analyses, the off-clamp
      RPN patients had a significantly shorter mean operative time (156 min compared
      with 185 min, p<0.001), a higher EBL (228 ml compared with 157 ml, p=0.009), and
      a smaller decrease in eGFR (2% compared with -6%, p=0.008). The retrospective
      analysis was the main limitation of this study. CONCLUSIONS: With appropriately
      selected patients and adequate surgeon experience, off-clamp RPN is safe and
      feasible. Off-clamp RPN was associated with higher EBL, shorter operative times,
      and smaller decrease in renal function.

PMID- 23122835
TI  - The role of health care communication in the development of complementary and
      integrative medicine.
AB  - In recent years, complementary medicine (CM) approaches are integrated within a
      growing number of health care services worldwide. Implementation of CM within
      primary, secondary and tertiary settings of health care requires attention to a
      variety of communication challenges. In this special issue of Patient Education
      and Counseling 23 articles are presented about the patient-provider communication
      on complementary approaches, and the implementation and integration of CM in
      health care. Parallel to CM integration in the clinical arena, this special issue
      emphasizes the importance of two complementary axes: in medical education and in
      research, particularly on management of chronic illness and life-threatening
      diseases. The three legs of the integrative stool--research, education, and
      clinical practice--are perceived in the light of open, non-judgmental patient
      health care provider-CM practitioner communication and a patient-centered bio
      psycho-social-cultural-spiritual agenda.

PMID- 23122837
TI  - [Orbital cysticercosis mimicking a painful third nerve palsy].
AB  - We report an atypical case of cysticercosis of the left levator-superior rectus
      complex, mimicking a painful partial third nerve palsy. The patient presented
      with painful diplopia, with limitation of elevation, depression and adduction of
      the left eye, associated with a ptosis of the upper left eyelid. Magnetic
      resonance imaging revealed two cysts, located within the left levator-superior
      rectus complex, and nine parenchymal cysts located in both hemispheres of the
      brain. Antibody titers directed against Cysticercus cellulosae were elevated as
      confirmed by Elisa and Immunoblot. Diplopia and local inflammation resolved after
      albendazole and systemic steroid treatment. Surgical resection of the cysts was
      unnecessary.

PMID- 23122836
TI  - Effects of an overnight intravenous lipid infusion on intramyocellular lipid
      content and insulin sensitivity in African-American versus Caucasian adolescents.
AB  - OBJECTIVE: To explain the predisposition for insulin resistance among African
      American (AA) adolescents, this study aimed to: 1) examine changes in
      intramyocellular lipid content (IMCL), and insulin sensitivity with intralipid
      (IL) infusion; and 2) determine whether the increase in IMCL is comparable
      between AA and Caucasian adolescents. MATERIALS AND METHODS: Thirteen AA and 15
      Caucasian normal-weight adolescents (BMI <85th) underwent a 3-h hyperinsulinemic
      euglycemic clamp, on two occasions in random order, after an overnight 12-h
      infusion of: 1) 20% IL and 2) normal saline (NS). IMCL was quantified by (1)H
      magnetic resonance spectroscopy in tibialis anterior muscle before and after IL
      infusion. RESULTS: During IL infusion, plasma TG, glycerol, FFA and fat oxidation
      increased significantly, with no race differences. Hepatic insulin sensitivity
      decreased with IL infusion with no difference between the groups. IL infusion was
      associated with a significant increase in IMCL, which was comparable between AA
      (Delta 105%; NS: 1.9+/-0.8 vs. IL: 3.9+/-1.6 mmol/kg wet weight) and Caucasian
      (Delta 86%; NS: 2.8+/-2.1 vs. IL: 5.2+/-2.4 mmol/kg wet weight), with similar
      reductions (P<0.01) in insulin sensitivity between the groups (Delta -44%: NS:
      9.1+/-3.3 vs. IL: 5.1+/-1.8 mg/kg/min per MUU/ml in AA) and (Delta -39%: NS:
      12.9+/-6.0 vs. IL: 7.9+/-3.8 mg/kg/min per MUU/ml in Caucasian) adolescents.
      CONCLUSIONS: In healthy adolescents, an acute elevation in plasma FFA with IL
      infusion is accompanied by significant increases in IMCL and reductions in
      insulin sensitivity with no race differential. Our findings suggest that AA
      normal-weight adolescents are not more susceptible than Caucasians to FFA-induced
      IMCL accumulation and insulin resistance.

PMID- 23122838
TI  - [Massive bilateral subconjunctival hemorrhage revealing acute lymphoblastic
      leukemia].
AB  - We report the case of 20-year-old patient who presented in emergency with
      bilateral massive, spontaneous subconjunctival hemorrhage. Clinical findings
      suggested a blood dyscrasia, which was confirmed by blood cell count. The patient
      was urgently referred to hematology where the diagnosis of acute lymphoblastic
      leukemia was made. This case highlights the importance of working up any unusual
      subconjunctival hemorrhage, as it may reveal, in certain cases, a severe life
      threatening disease.

PMID- 23122839
TI  - The association of AGTR2 polymorphisms with preeclampsia and uterine artery
      bilateral notching is modulated by maternal BMI.
AB  - INTRODUCTION: This study aimed to determine the association of AGTR1 and AGTR2
      polymorphisms with preeclampsia and whether these are affected by environmental
      factors and fetal sex. METHODS: Overall 3234 healthy nulliparous women, their
      partners and babies were recruited prospectively to the SCOPE study in Adelaide
      and Auckland. Data analyses were confined to 2121 Caucasian parent-infant trios,
      among whom 123 had preeclamptic pregnancies. 1185 uncomplicated pregnancies
      served as controls. DNA was extracted from buffy coats and genotyped by utilizing
      the Sequenom MassARRAY system. Doppler sonography on the uterine arteries was
      performed at 20 weeks' gestation. RESULTS: Four polymorphisms in AGTR1 and AGTR2
      genes, including AGTR1 A1166C, AGTR2 C4599A, AGTR2 A1675G and AGTR2 T1134C, were
      selected and significant associations were predominately observed for AGTR2
      C4599A. When the cohort was stratified by maternal BMI, in women with BMI >= 25
      kg/m(2), the AGTR2 C4599A AA genotype in mothers and neonates was associated with
      an increased risk for preeclampsia compared with the CC genotype [adjusted OR 2.1
      (95% CI 1.0-4.2) and adjusted OR 3.0 (95% CI 1.4-6.4), respectively]. In the same
      subset of women, paternal AGTR2 C4599A A allele was associated with an increased
      risk for preeclampsia and uterine artery bilateral notching at 20 weeks'
      gestation compared with the C allele [adjusted OR 1.9 (95% CI 1.1-3.3) and
      adjusted OR 2.1 (95% CI 1.3-3.4), respectively]. CONCLUSION: AGTR2 C4599A in
      mothers, fathers and babies was associated with preeclampsia and this association
      was only apparent in pregnancies in which the women had a BMI >= 25 kg/m(2),
      suggesting a gene-environment interaction.

PMID- 23122840
TI  - [Clinical and pharmacological study of the efficacy of carbetocin in elective
      caesareans compared to low and usual doses of oxytocin].
AB  - OBJECTIVES: To evaluate uterine contractility, bleeding, haemodynamic
      performance, and side effects of different doses of oxytocin after delivery under
      spinal anaesthesia in caesarean section without prior labour in childbirth. We
      also perform a pharmacoeconomic evaluation. MATERIAL AND METHODS: A randomised,
      descriptive, observational and multicentre prospective study was conducted, which
      included 104 ASA 1 patients divided into 3 groups. Group 1 (n=52) received after
      removal of the foetus and coinciding with foetal umbilical cord clamping, 1 IU of
      oxytocin followed by an infusion of 2.5 UI*h(-1); Group 2 (n=52) a continuous
      infusion of 20IU oxytocin at a rate of 700mUI*min(-1) followed later by 10UI*h(
      1), and group 3, 100MUg bolus dose of carbetocin only. RESULTS: There were no
      statistical differences between groups in anthropometric, obstetric or
      anaesthetic variables. Significant differences in uterine contraction in vaginal
      bleeding and the incidence of side effects, particularly headache and tremor,
      were more pronounced in the carbetocin group. CONCLUSIONS: With these results, we
      cannot recommend the routine use of carbetocin in caesarean sections, because it
      is accompanied by an increased incidence of side effects without any improvement
      in the prevention of obstetric haemorrhage. Finally, it is economically more
      expensive than the use of low doses of oxytocin, which may be the trend that
      should be considered in the future, due to the clinical outcomes, and its lower
      cost.

PMID- 23122841
TI  - Loss of O6-methylguanine-DNA methyltransferase confers collateral sensitivity to
      carmustine in topoisomerase II-mediated doxorubicin resistant triple negative
      breast cancer cells.
AB  - Triple-negative breast cancer is characterized by aggressive tumours whose cells
      lack oestrogen and progesterone receptors and do not over-express HER2. It
      accounts for approximately 10-15% of breast cancer cases. We sought to generate a
      cellular model of chemotherapy drug resistance for this type of disease to
      provide the tools for the development of new therapies. Doxorubicin is a
      component of some chemotherapy regimes used to treat this form of cancer but
      resistance preventing disease eradication frequently occurs, mainly due to over
      expression of drug transporters such as P-glycoprotein. CALDOX cells were
      generated by exposure of CAL51 to doxorubicin. Resistance to doxorubicin did not
      involve drug transporters, as the both parental and resistant cells accumulated
      doxorubicin to comparable levels. CALDOX cells had slower proliferation rate and
      an extended G1 cell cycle stage than the parental line, mainly due to an
      intrinsic activation of CDNK1 (p21), but this cell cycle block was not involved
      in the mechanism of resistance. CALDOX cells had reduced levels of TOP2A
      (topoisomerase IIalpha) and were cross resistant to the topoisomerase II
      inhibitors etoposide and mitoxantrone. CALDOX cells showed collateral sensitivity
      to carmustine due to the lack of O6-methylguanine-DNA-methyltransferase (MGMT)
      expression, related to the hypermethylation of its promoter. The collateral
      sensitivity of CALDOX cells to carmustine provides the rationale to evaluate MGMT
      promoter methylation status to design better therapeutic strategies for triple
      negative breast cancer.

PMID- 23122842
TI  - Oxidative stress and cholinesterase inhibition in plasma, erythrocyte and brain
      of rats' pups following lactational exposure to malathion.
AB  - The organophosphorus (OP) pesticide malathion is a highly neurotoxic compound.
      Some studies have reported neurotoxicity signs after in utero exposure to OP
      pesticides. However there is no evidence of the exclusive contribution of the
      lactational exposure to malathion as a possible cause of neurotoxicity in rats'
      pups. In this respect, we investigated the exclusive contribution of malathion
      (200 mg/kg, b.w.) exposure through maternal milk in rat pups during lactation. We
      evaluated the activity of acetylcholinesterase (AChE) and butyrylcholinesterase
      (BChE), as well as on biochemical parameters related to the oxidative stress such
      lipoperoxidation and antioxidant enzyme activities as superoxide dismutase (SOD)
      and catalase (CAT) in the brain, plasma and erythrocytes of rats' pups at 21st
      postnatal day (Pnd). These parameters were also evaluated in the same tissues but
      at 51 Pnd. Our results showed that the malathion exposure during lactation
      induced a high inhibitory effect of the brain, plasma and erythrocyte AChE and
      BChE activities in rat pups. Many changes were observed in the biochemical
      parameters related to the oxidative stress for pups brain, plasma and
      erythrocyte. The present study shows, for the first time, that the exposure of
      postnatal pups to malathion via lactation inhibits the activity of brain, plasma
      and erythrocytes cholinesterase in the pups. These findings suggest that
      malathion exposure during lactation induced a cerebral alterations and oxidative
      stress in rat pups.

PMID- 23122843
TI  - A common signaling process that promotes mycorrhizal and oomycete colonization of
      plants.
AB  - The symbiotic association between plants and arbuscular mycorrhizal fungi is
      almost ubiquitous within the plant kingdom, and the early stages of the
      association are controlled by plant-derived strigolactones acting as a signal to
      the fungus in the rhizosphere and lipochito-oligosaccharides acting as fungal
      signals to the plant. Hyphopodia form at the root surface, allowing the initial
      invasion, and this is analogous to appressoria, infection structures of
      pathogenic fungi and oomycetes. Here, we characterize RAM2, a gene of Medicago
      truncatula required for colonization of the root by mycorrhizal fungi, which is
      necessary for appropriate hyphopodia and arbuscule formation. RAM2 encodes a
      glycerol-3-phosphate acyl transferase (GPAT) and is involved in the production of
      cutin monomers. Plants defective in RAM2 are unable to be colonized by arbuscular
      mycorrhizal fungi but also show defects in colonization by an oomycete pathogen,
      with the absence of appressoria formation. RAM2 defines a direct signaling
      function, because exogenous addition of the C16 aliphatic fatty acids associated
      with cutin are sufficient to promote hyphopodia/appressoria formation. Thus,
      cutin monomers act as plant signals that promote colonization by arbuscular
      mycorrhizal fungi, and this signaling function has been recruited by pathogenic
      oomycetes to facilitate their own invasion.

PMID- 23122844
TI  - Precision of hunchback expression in the Drosophila embryo.
AB  - Activation of the gap gene hunchback (hb) by the maternal Bicoid gradient is one
      of the most intensively studied gene regulatory interactions in animal
      development. Most efforts to understand this process have focused on the
      classical Bicoid target enhancer located immediately upstream of the P2 promoter.
      However, hb is also regulated by a recently identified distal shadow enhancer as
      well as a neglected "stripe" enhancer, which mediates expression in both central
      and posterior regions of cellularizing embryos. Here, we employ BAC transgenesis
      and quantitative imaging methods to investigate the individual contributions of
      these different enhancers to the dynamic hb expression pattern. These studies
      reveal that the stripe enhancer is crucial for establishing the definitive border
      of the anterior Hb expression pattern, just beyond the initial border delineated
      by Bicoid. Removal of this enhancer impairs dynamic expansion of hb expression
      and results in variable cuticular defects in the mesothorax (T2) due to abnormal
      patterns of segmentation gene expression. The stripe enhancer is subject to
      extensive regulation by gap repressors, including Kruppel, Knirps, and Hb itself.
      We propose that this repression helps ensure precision of the anterior Hb border
      in response to variations in the Bicoid gradient.

PMID- 23122845
TI  - A GRAS-type transcription factor with a specific function in mycorrhizal
      signaling.
AB  - Legumes establish mutualistic associations with mycorrhizal fungi and with
      nitrogen-fixing rhizobial bacteria. These interactions occur following plant
      recognition of Nod factor from rhizobial bacteria and Myc factor from mycorrhizal
      fungi. A common symbiosis signaling pathway is involved in the recognition of
      both Nod factor and Myc factor and is required for the establishment of these two
      symbioses. The outcomes of these associations differ, and therefore, despite the
      commonality in signaling, there must be mechanisms that allow specificity. In Nod
      factor signaling, a complex of GRAS-domain transcription factors controls gene
      expression downstream of the symbiosis signaling pathway. Here, we show that a
      GRAS-domain transcription factor, RAM1, functions in mycorrhizal-specific
      signaling. Plants mutated in RAM1 are unable to be colonized by mycorrhizal
      fungi, with a defect in hyphopodia formation on the surface of the root. RAM1 is
      specifically required for Myc factor signaling and appears to have no role in Nod
      factor signaling. RAM1 regulates the expression of RAM2, a glycerol-3-phosphate
      acyl transferase that promotes cutin biosynthesis to enhance hyphopodia
      formation. We conclude that mycorrhizal signaling downstream of the symbiosis
      signaling pathway has parallels with nodulation-specific signaling and functions
      to promote mycorrhizal colonization by regulating cutin biosynthesis.

PMID- 23122846
TI  - An Asian elephant imitates human speech.
AB  - Vocal imitation has convergently evolved in many species, allowing learning and
      cultural transmission of complex, conspecific sounds, as in birdsong. Scattered
      instances also exist of vocal imitation across species, including mockingbirds
      imitating other species or parrots and mynahs producing human speech. Here, we
      document a male Asian elephant (Elephas maximus) that imitates human speech,
      matching Korean formants and fundamental frequency in such detail that Korean
      native speakers can readily understand and transcribe the imitations. To create
      these very accurate imitations of speech formant frequencies, this elephant
      (named Koshik) places his trunk inside his mouth, modulating the shape of the
      vocal tract during controlled phonation. This represents a wholly novel method of
      vocal production and formant control in this or any other species. One
      hypothesized role for vocal imitation is to facilitate vocal recognition by
      heightening the similarity between related or socially affiliated individuals.
      The social circumstances under which Koshik's speech imitations developed suggest
      that one function of vocal learning might be to cement social bonds and, in
      unusual cases, social bonds across species.

PMID- 23122847
TI  - Social signals in primate orbitofrontal cortex.
AB  - Primate evolution produced an increased capacity to respond flexibly to varying
      social contexts as well as expansion of the prefrontal cortex. Despite this
      association, how prefrontal neurons respond to social information remains
      virtually unknown. People with damage to their orbitofrontal cortex (OFC)
      struggle to recognize facial expressions, make poor social judgments, and
      frequently make social faux pas. Here we test explicitly whether neurons in
      primate OFC signal social information and, if so, how such signals compare with
      responses to primary fluid rewards. We find that OFC neurons distinguish images
      that belong to socially defined categories, such as female perinea and faces, as
      well as the social dominance of those faces. These modulations signaled both how
      much monkeys valued these pictures and their interest in continuing to view them.
      Far more neurons signaled social category than signaled fluid value, despite the
      stronger impact of fluid reward on monkeys' choices. These findings indicate that
      OFC represents both the motivational value and attentional priority of other
      individuals, thus contributing to both the acquisition of information about
      others and subsequent social decisions. Our results betray a fundamental
      disconnect between preferences expressed through overt choice, which were
      primarily driven by the desire for more fluid, and preferential neuronal
      processing, which favored social computations.

PMID- 23122848
TI  - Enhancing social ability by stimulating right temporoparietal junction.
AB  - The temporoparietal junction (TPJ) is a key node within the "social brain".
      Several studies suggest that the TPJ controls representations of the self or
      another individual across a variety of low-level (agency discrimination, visual
      perspective taking, control of imitation) and high-level (mentalizing, empathy)
      sociocognitive processes. We explored whether sociocognitive abilities relying on
      on-line control of self and other representations could be modulated with
      transcranial direct current stimulation (tDCS) of TPJ. Participants received
      excitatory (anodal), inhibitory (cathodal), or sham stimulation before completing
      three sociocognitive tasks. Anodal stimulation improved the on-line control of
      self-other representations elicited by the imitation and perspective-taking tasks
      while not affecting attribution of mental states during a self-referential task
      devoid of such a requirement. Our findings demonstrate the efficacy of tDCS to
      improve social cognition and highlight the potential for tDCS to be used as a
      tool to aid self-other processing in clinical populations.

PMID- 23122849
TI  - Oskar predates the evolution of germ plasm in insects.
AB  - oskar is the only gene in the animal kingdom necessary and sufficient for
      specifying functional germ cells. However, oskar has only been identified in
      holometabolous ("higher") insects that specify their germline using specialized
      cytoplasm called germ plasm. Here we show that oskar evolved before the
      divergence of higher insects and provide evidence that its germline role is a
      recent evolutionary innovation. We identify an oskar ortholog in a basally
      branching insect, the cricket Gryllus bimaculatus. In contrast to Drosophila
      oskar, Gb-oskar is not required for germ cell formation or axial patterning.
      Instead, Gb-oskar is expressed in neuroblasts of the brain and CNS and is
      required for neural development. Taken together with reports of a neural role for
      Drosophila oskar, our data demonstrate that oskar arose nearly 50 million years
      earlier in insect evolution than previously thought, where it may have played an
      ancestral neural role, and was co-opted to its well-known essential germline role
      in holometabolous insects.

PMID- 23122852
TI  - Biospecimens, biomarkers, and burgeoning data: the imperative for more rigorous
      research standards.
AB  - Knowledge of the altered molecular landscapes in disease offers great promise for
      developing biomarker-based tests to improve diagnosis and optimize treatment.
      Progress in biomarker research has been frustratingly slow due to the poor
      clinical trial design and the lack of standards for specimen collection,
      biomarker analysis, and data reporting. The ability of high throughput genomics,
      proteomics, and other 'omics' platforms to profile a large number of analytes in
      a single assay, together with the pending prospect of rapid expansion of whole
      exome and whole genome sequencing for clinical use, is increasing the technical
      and logistical complexity of biomarker validation. Harnessing these new
      technologies and improved productivity in biomarker validation will depend on
      adopting systems-based approaches and require major changes in the organization
      and funding strategies for biomarker research. A systems approach will require
      new multi-institution collaborations, the integration of diverse technical and
      clinical activities, greater engagement of industry, and education of regulators,
      clinicians, and payers about how to use biomarkers for improved patient
      management and clinical outcomes.

PMID- 23122850
TI  - Microtubules enable the planar cell polarity of airway cilia.
AB  - BACKGROUND: Airway cilia must be physically oriented along the longitudinal
      tissue axis for concerted, directional motility that is essential for proper
      mucociliary clearance. RESULTS: We show that planar cell polarity (PCP) signaling
      specifies directionality and orients respiratory cilia. Within all airway
      epithelial cells, a conserved set of PCP proteins shows interdependent,
      asymmetric junctional localization; nonautonomous signaling coordinates
      polarization between cells; and a polarized microtubule (MT) network is likely
      required for asymmetric PCP protein localization. We find that basal bodies dock
      after polarity of PCP proteins is established and are polarized nearly
      simultaneously, and that refinement of basal body/cilium orientation continues
      during airway epithelial development. Unique to mature multiciliated cells, we
      identify PCP-regulated, planar polarized MTs that originate from basal bodies and
      interact, via their plus ends, with membrane domains associated with the PCP
      proteins Frizzled and Dishevelled. Disruption of MTs leads to misoriented cilia.
      CONCLUSIONS: A conserved PCP pathway orients airway cilia by communicating
      polarity information from asymmetric membrane domains at the apical junctions,
      through MTs, to orient the MT and actin-based network of ciliary basal bodies
      below the apical surface.

PMID- 23122853
TI  - Toponome imaging system: multiplex biomarkers in oncology.
AB  - Toponome imaging systems (TIS) can yield high-resolution subcellular
      colocalization images of multiple proteins within single cells and intact tissue
      sections, giving this technology significant potential for identifying multiplex
      biomarkers that simultaneously measure several aspects of a cell. The integral
      role of the microenvironment in malignant progression and the recently
      appreciated heterogeneity of cancer cells underscore the importance of
      characterizing complex molecular phenotypes and the large protein network
      structures of single cells within their preserved anatomical context. Here, we
      discuss the TIS technique and the potential for developing new sensitive and
      specific multiplex biomarkers for risk stratification and diagnosis, in addition
      to its utility for anticancer drug discovery by identifying 'hub' proteins that
      are essential regulators of protein networks.

PMID- 23122854
TI  - Coat proteins, host factors and plant viral replication.
AB  - It was once believed that the sole biological function of viral coat protein (CP)
      is to encapsidate the viral genome, protecting it from degradation. The past
      several decades have witnessed a shift in this paradigm towards recognizing CPs
      as multifunctional proteins involved in almost every stage of the viral infection
      cycle. Such functional diversity is achieved via specific CP interactions with
      viral and host components in the infected cell. Different CP functions are
      tightly regulated both temporally and spatially through a variety of mechanisms
      including post-translational modifications and competing interactions. In the
      present review, we summarize the non-structural functions of plant viral CPs,
      placing special emphasis on their roles in viral genome replication and
      translation.

PMID- 23122856
TI  - Host factors with regulatory roles in tombusvirus replication.
AB  - Similar to animal viruses, the abundant plant positive-strand RNA viruses
      replicate in infected cells by exploiting the vast resources of the host. This
      review focuses on virus-host interactions during tombusvirus replication. The
      multifunctional tombusvirus p33 replication protein not only interacts with
      itself, the viral p92(pol) polymerase, and viral RNA, but also with approximately
      100 cellular proteins and subcellular membranes. Several negative regulatory host
      proteins, such as cyclophilins and WW motif containing proteins, also bind to p33
      and interfere with p33's functions. To explain how p33 can perform multiple
      functions, we propose that a variety of interactions involving p33 result in the
      commitment of p33 molecules to specific tasks. This facilitates tight spatial and
      temporal organization of viral replication in infected cells.

PMID- 23122857
TI  - Sulfanylphthalonitrile analogues as selective and potent inhibitors of monoamine
      oxidase B.
AB  - It has recently been reported that nitrile containing compounds frequently act as
      potent monoamine oxidase B (MAO-B) inhibitors. Modelling studies suggest that
      this high potency inhibition may rely, at least in part, on polar interactions
      between nitrile functional groups and polar moieties within the MAO-B substrate
      cavity. In an attempt to identify potent and selective inhibitors of MAO-B and to
      contribute to the known structure-activity relationships of MAO inhibition by
      nitrile containing compounds, the present study examined the MAO inhibitory
      properties of series of novel sulfanylphthalonitriles and sulfanylbenzonitriles.
      The results document that the evaluated compounds are potent and selective MAO-B
      inhibitors with most homologues possessing IC(50) values in the nanomolar range.
      In general, the sulfanylphthalonitriles exhibited higher binding affinities for
      MAO-B than the corresponding sulfanylbenzonitrile homologues. Among the compounds
      evaluated, 4-[(4-bromobenzyl)sulfanyl]phthalonitrile is a particularly promising
      inhibitor since it displayed a high degree of selectivity (8720-fold) for MAO-B
      over MAO-A, and potent MAO-B inhibition (IC(50)=0.025 MUM). Based on these
      observations, this structure may serve as a lead for the development of therapies
      for neurodegenerative disorders such as Parkinson's disease.

PMID- 23122855
TI  - Cell-based genomic screening: elucidating virus-host interactions.
AB  - Viruses rely on host cell machinery for successful infection, while at the same
      time evading the host immune response. Characterization of these processes has
      revealed insights both into fundamental cellular processes as well as the nuances
      of viral replication. The recent advent of cell-based screening coupled with RNAi
      technology, has greatly facilitated studies focused on characterizing the virus
      host interface and has expanded our understanding of cellular factors that impact
      viral infection. These findings have led to the discovery of potential
      therapeutic targets, but there is certainly more to be discovered. In this
      article we will review the recent progress in this arena and discuss the
      challenges and future of this emerging field.

PMID- 23122858
TI  - Preparation and characterization of phospholipid-conjugated indocyanine green as
      a near-infrared probe.
AB  - We have rationally designed and synthesized a novel near-infrared (NIR)
      photoactivating probe, designated by iDOPE, in which an indocyanine green (ICG)
      fluorophore is covalently conjugated with a phospholipid moiety, 1,2-dioleoyl-sn
      glycero-3-phosphoethanolamine (DOPE), to incorporate into liposome bilayers. NIR
      irradiation showed that iDOPE retained the optical and fluorescence properties of
      ICG and demonstrated photoactivator characteristics: fluorescence emission at
      around 820 nm in a solvent, singlet oxygen production, and concentration
      dependent heat generation. Additionally, iDOPE was incorporated into liposome
      bilayers and maintained stable liposomally formulated iDOPE (LP-iDOPE) over 1week
      under physiological conditions. We also observed the tumor-specific
      biodistribution of LP-iDOPE of in vivo xenografts. These findings suggest that LP
      iDOPE might be a promising tool for NIR optical imaging, photodynamic therapy,
      and photothermal therapy.

PMID- 23122859
TI  - Discovery and optimization of a series of 2-aminothiazole-oxazoles as potent
      phosphoinositide 3-kinase gamma inhibitors.
AB  - A novel series of 2-aminothiazole-oxazoles was designed and synthesized as part
      of efforts to develop potent phosphoinositide 3-kinase gamma (PI3Kgamma)
      inhibitors. The modification of a high-throughput screening hit, compound 1,
      resulted in the identification of compounds 10 and 15, which displayed potent
      inhibitory activities in enzyme-based and cell-based assays.

PMID- 23122860
TI  - Structure based medicinal chemistry approach to develop 4-methyl-7-deazaadenine
      carbocyclic nucleosides as anti-HCV agent.
AB  - The structure-based approaches were implemented to design and rationally select
      the molecules for synthesis and anti-HCV activity evaluation. The systematic
      structure-activity relationships of previously discovered molecules (types I, II,
      III) were analyzed to design new molecules (type IV) by bioisosteric replacement
      of the amino group. The ligand conformation, binding mode studies and drug like
      properties were major determinant for selection of molecules for final synthesis.
      The replacement of amino group with methyl restored the interactions with RNA
      template (Tem 799) through bifurcated weak H-bond (C-H...O). This is an
      interesting finding observed from molecular modeling studies. It was found that
      6c-e has anti-HCV activity (EC(50) in 37-46 MUM) while 6a, 6b and 6g were
      inactive. The compound 6f (EC(50) 28 MUM) was the most active among the series
      however it also showed some cytotoxicity (CC(50) 52.8 MUM). Except 6f, none of
      the compounds were found to be cytotoxic (CC(50)>100 MUM). The present study
      discloses structure-based approach for novel anti-HCV lead discovery and opens a
      future scope of lead optimization.

PMID- 23122861
TI  - Uronosyl phosphonate-based sialidase inhibitor synthesis and conformational
      analysis.
AB  - With a view to development of novel sialidase inhibitors, mimetics of the natural
      inhibitor Neu5Ac2en have been prepared in which a phosphonate group replaces the
      sialic acid glycerol side chain. Different hex-4-en derivatives adopt half-chair
      conformations that place the glycosyl phosphonate in an equatorial position. For
      the alpha-L-threo-hex-4-en derivative this conformation is equivalent to that of
      Neu5Ac2en, and opposite to that seen for alkyl O-glycosides with the same overall
      stereochemistry.

PMID- 23122862
TI  - Synthesis and antibacterial activity of novel modified 5-O-desosamine ketolides.
AB  - A series of novel modified 5-O-desosamine-ketolides were synthesized. The 5-O
      desosamine fragment was removed from ketolide by an efficient and mild
      manipulation. 4-O-substituted desosamine was introduced into the ketolide aglycon
      and various coupling methods were essayed for the glycosylation. Three novel
      ketolides were tested for in vitro antibacterial activity against a panel of
      susceptible and resistant pathogens. Compound 26 showed potent activity against
      all the methicillin-sensitivity and resistant pathogens.

PMID- 23122863
TI  - A regio- and stereoselective 1,3-dipolar cycloaddition for the synthesis of new
      fangled dispiropyrrolothiazoles as antimycobacterial agents.
AB  - A series of dispiropyrrolothiazoles compounds were synthesized using 1,3-dipolar
      cycloaddition and were screened for antimycobacterial activity against
      Mycobacterium tuberculosis H(37)Rv and INH resistant M. tuberculosis strains. Two
      of them were showing good activity with MIC of less than 1 MUM. Compound (5f) was
      found to be the most active with MIC of 0.210 and 8.312 MUM respectively.

PMID- 23122864
TI  - Isocytosine-based inhibitors of xanthine oxidase: design, synthesis, SAR, PK and
      in vivo efficacy in rat model of hyperuricemia.
AB  - Structure-activity relationship studies were carried out for lead generation
      following structure-guided design approach from an isocytosine scaffold
      identified earlier for xanthine oxidase inhibition. A 470-fold improvement in in
      vitro IC(50) was obtained in the process. Five most potent compounds with
      nanomolar IC(50) values were selected for pharmacokinetics and in vivo
      experiments. The best compound showed good in vivo activity when administered
      intraperitoneally but was not active by oral route. The results suggest that
      improvement in oral exposure could improve the in vivo efficacy of this series.

PMID- 23122865
TI  - Identification of selective inhibitors of indoleamine 2,3-dioxygenase 2.
AB  - The kynurenine pathway is responsible for the breakdown of the majority of the
      essential amino acid, tryptophan (Trp). The first and rate-limiting step of the
      kynurenine pathway can be independently catalysed by tryptophan 2,3-dioxygenase
      (Tdo2), indoleamine 2,3-dioxygenase 1 (Ido1) or indoleamine 2,3-dioxygenase 2
      (Ido2). Tdo2 or Ido1 enzymatic activity has been implicated in a number of
      actions of the kynurenine pathway, including immune evasion by tumors. IDO2 is
      expressed in several human pancreatic cancer cell lines, suggesting it also may
      play a role in tumorigenesis. Although Ido2 was originally suggested to be a
      target of the chemotherapeutic agent dextro-1-methyl-tryptophan, subsequent
      studies suggest this compound does not inhibit Ido2 activity. The development of
      selective Ido2 inhibitors could provide valuable tools for investigating its
      activity in tumor development and normal physiology. In this study, a library of
      Food and Drug Administration-approved drugs was screened for inhibition of mouse
      Ido2 enzymatic activity. A number of candidates were identified and IC(50) values
      of each compound for Ido1 and Ido2 were estimated. The Ido2 inhibitors were also
      tested for inhibition of Tdo2 activity. Our results showed that compounds from a
      class of drugs used to inhibit proton pumps were the most potent and selective
      Ido2 inhibitors identified in the library screen. These included tenatoprazole,
      which exhibited an IC(50) value of 1.8MUM for Ido2 with no inhibition of Ido1 or
      Tdo2 activity detected at a concentration of 100MUM tenatoprazole. These highly
      selective Ido2 inhibitors will be useful for defining the distinct biological
      roles of the three Trp-catabolizing enzymes.

PMID- 23122866
TI  - An ecofriendly synthesis and DNA binding interaction study of some pyrazolo [1,5
      a]pyrimidines derivatives.
AB  - The DNA molecule is a target for plethora of anticancer and antiviral drugs that
      forms covalent and non-covalent adducts with major or minor groove of DNA. In
      present study we synthesized series of novel Pyrazolo [1,5-a]pyrimidine
      derivatives. The newly synthesized compounds were characterized by elemental
      analysis, IR, (1)H NMR, and mass spectral data. The selected compounds were
      studied for interaction with Calf thymus DNA (CT-DNA) using electronic spectra,
      viscosity measurement and thermal denaturation studies. Further, molecular
      interactions were revealed for compound IIIa and IVa by computational
      methodologies. The preferred mode of ligand binding with double helical DNA as
      well as preferable DNA groove were explored by molecular docking in different DNA
      models.

PMID- 23122867
TI  - 7-Phenyl-pyrido[2,3-d]pyrimidine-2,4-diamines: novel and highly selective protein
      tyrosine phosphatase 1B inhibitors.
AB  - High throughput screening of the Roche compound collection led to the
      identification of diaminopyrroloquinazoline series as a novel class of PTP1B
      inhibitors. Structural modification of diaminopyrroloquinazoline series resulted
      in pyrido[2,3-d]pyrimidine-2,4-diamine series which was further optimized to give
      compounds 5 and 24 as potent, selective (except T-cell phosphatase) PTP1B
      inhibitors with good mouse PK properties.

PMID- 23122868
TI  - Riccardin C derivatives as anti-MRSA agents: structure-activity relationship of a
      series of hydroxylated bis(bibenzyl)s.
AB  - Members of a series of macrocyclic bis(bibenzyl) riccardin-class derivatives were
      found to exhibit antibacterial activity towards methicillin-resistant
      Staphylococcus aureus (anti-MRSA activity). Structure-activity relationship (SAR)
      studies were conducted, focusing on the number and position of the hydroxyl
      groups. The minimum essential structure for anti-MRSA activity was also
      investigated.

PMID- 23122869
TI  - Wetlands, climate zones and Barmah Forest virus disease in Queensland, Australia.
AB  - Barmah Forest virus (BFV) disease is the second most common mosquito-borne
      disease in Australia, but the linkages of the wetlands and climate zones with BFV
      transmission remain unclear. We aimed to examine the relationship between the
      wetlands, climate zones and BFV risk in Queensland, Australia. Data on the
      wetlands, climate zones, population and BFV cases for the period 1992 to 2008
      were obtained from relevant government agencies. BFV risk was grouped as low-,
      medium- and high-level based on BFV incidence percentiles. The buffer zones
      around each BFV case were made using 1, 5, 10, 15, 20, 25 and 50km distances. We
      performed a discriminant analysis to determine the differences between wetland
      classes and BFV risk within each climate zone. The discriminant analyses show
      that saline 1, riverine and saline tidal influence were the most significant
      contributors to BFV risk in all climate and buffer zones, while lacustrine,
      palustrine, estuarine and saline 2 and saline 3 wetlands were less important.
      These models had classification accuracies of 76%, 98% and 100% for BFV risk in
      subtropical, tropical and temperate climate zones, respectively. This study
      demonstrates that BFV risk varies with wetland class and climate zone. The
      discriminant analysis is a useful tool to quantify the links between wetlands,
      climate zones and BFV risk.

PMID- 23122870
TI  - Seasonal variability of antioxidant biomarkers in mud crabs (Scylla serrata).
AB  - Studies on oxidative stress (OS) in crustacea are widely used as ecotoxicological
      indices to assess the environment risk produced by the impact of several stressor
      and pollutants. In the present study, effects of seasonality on OS physiology
      markers such as antioxidant enzymes (superoxide dismutase, catalase, glutathione
      peroxidase and glutathione reductase), small antioxidant molecules (ascorbic acid
      and reduced glutathione), oxidative stress indices (lipid peroxidation, protein
      carbonylation and hydrogen peroxide) and total antioxidant capacity in
      hepatopancreas, gills and abdominal muscle of adult mud crab Scylla serrata,
      sampled from Chilika lagoon of India, were determined in winter, summer and rainy
      seasons. Results indicate that variations in enzymatic and non-enzymatic
      antioxidants with relation to season were not only tissue specific but also were
      gender specific. The levels of OS parameters were higher in hepatopancreas in
      comparison to gills and abdominal muscle of the crabs in all seasons. OS indices
      in tissues of the crabs were mainly higher in summer season when temperature and
      salinity of the lagoon were high with low oxygen content. Although OS was lower
      in winter season and moderate in rainy season in tissues of male crabs, it was
      higher in gills and hepatopancreas of females in rainy season. Correlation
      analyses between hydrological parameters of the lagoon (temperature, salinity and
      dissolved oxygen content) and OS physiology parameters in tissues of crabs
      suggest that abiotic factors influence the levels of antioxidant enzymes and,
      thereby the OS status in a tissue and sex specific manner. Collectively, the
      results of the present work suggest that further investigation is warranted
      before using OS parameters in S. serrata as biomarkers to monitor estuarine
      environment as these are influenced by gender, tissue and season.

PMID- 23122871
TI  - Oxyntomodulin attenuates exendin-4-induced hypoglycemia in cattle.
AB  - Oxyntomodulin (OXM), glucagon, glucagon-like peptide-1 (GLP-1), and exendin-4 (Ex
      4) are peptide hormones that regulate glucose homeostasis in monogastric and
      ruminant animals. Recently, we reported that the insulin-releasing effects of OXM
      and glucagon in cattle are mediated through both GLP-1 and glucagon receptors.
      The purpose of this study was to examine the mechanisms of the glucoregulatory
      actions induced by Ex-4, GLP-1, OXM, and glucagon and the interrelationships
      among these hormones in cattle. Two experiments were performed in Holstein
      cattle. In Experiment 1, we initially assessed the effects of intravenous (iv)
      bolus injection of 0, 0.25, 1, and 2 MUg/kg body weight (BW) of Ex-4, GLP-1, and
      OXM on insulin and glucose concentrations in 3-mo-old intact male Holstein
      calves. In Experiment 2, we studied insulin and glucose responses to iv
      coinjection of 0.25 MUg of Ex-4 or GLP-1/kg BW with 2 MUg of OXM or glucagon/kg
      BW in 4-mo-old Holstein steers. Administration of peptides and blood sampling
      were done via a jugular catheter. Plasma was separated and the concentrations of
      peptides and glucose in plasma were analyzed using radioimmunoassay and enzymatic
      methods, respectively. Results showed that the potent glucoregulatory action of
      Ex-4 in 4-mo-old steers was delayed and attenuated when Ex-4 was coinjected with
      OXM. The decline in plasma glucose concentrations began at 5 min in the Ex-4
      injected group (P < 0.05) vs 15 min in the Ex-4 + OXM-injected group (P < 0.05).
      Plasma concentrations of glucose at 30 min were reduced 26% from basal
      concentrations in the Ex-4-injected group and 13% in the Ex-4 + OXM-injected
      group (P < 0.001). Results also showed that the glucose concentrations initially
      increased in the Ex-4 + glucagon-treated group, but declined to a relatively
      hypoglycemic condition by 90 to 120 min. In contrast, the glucose concentrations
      at specific time points between the GLP-1 + OXM-injected group and the OXM
      injected group did not differ. Similarly, the glucose concentrations in the GLP-1
      + glucagon-injected group did not differ from those in the glucagon-injected
      group. Because OXM and glucagon mediate glucose concentrations via the glucagon
      receptor, it is suggested that the potent glucose-lowering action of Ex-4 might
      include the glucagon receptor antagonistic action of Ex-4.

PMID- 23122872
TI  - Aesthetic analysis in rhinoplasty: surgeon vs. patient perspectives: a
      prospective, blinded study.
AB  - OBJECTIVE: To determine how patients seeking cosmetic rhinoplasty analyze
      themselves compared to their surgeon's analysis. Simply stated, "Does your
      surgeon view your nose the same as you?" STUDY DESIGN: Prospective, blinded
      study. METHODS: All primary rhinoplasty consultations completed a nasal analysis
      questionnaire. The patients' facial plastic surgeons completed an identical
      questionnaire. The results were compared and analyzed. RESULTS: Data underwent
      statistical analysis and subsequent factor analysis was performed. 132 patients
      participated in the study. Questions were grouped together based on factors:
      overall appearance, skin quality, tip dimensions, straightness, nostril show, and
      width. The only factor with reasonable surgeon/patient correlation was factor 1,
      overall appearance, with correlation 0.6473, p<0.001. CONCLUSIONS: Surgeons and
      patients are in agreement with the overall appearance of the nose, but differ in
      their analysis regarding the details. This information can be used to guide
      future discussions during consultations and most importantly help to better gauge
      and manage patient expectations.

PMID- 23122873
TI  - The potential of accelerometers in the evaluation of stability of total knee
      arthroplasty.
AB  - An accelerometer attached to the anterior proximal tibia was investigated as an
      evaluation of knee stability of Total Knee Arthroplasty (TKA) patients while
      performing daily activities. Acceleration data of 38 TKA knees with a minimum
      follow up of 6months were compared with 34 control knees. The activities
      performed were: walking three steps forward and coming to a sudden stop; turning
      in the direction of non-tested knee; sit-to-stand; and stepping up and down from
      a 7 inch step. The acceleration results showed significant differences between
      TKA and controls while stepping down and while turning in the non-tested knee
      direction. The higher accelerations with the TKA group may have represented an
      objective measure of stability, even if this was not directly discernible to the
      patient.

PMID- 23122874
TI  - Unilateral free vascularized fibula shared for the treatment of bilateral
      osteonecrosis of the femoral head.
AB  - Between June 2007 and May 2008, 21 patients with bilateral osteonecrosis of the
      femoral head were surgically treated with implantation of free vascularized
      fibula obtained from the unilateral donor site. All patients were followed up
      clinically and radiographically for an average of 3.5 years. The evaluation
      included operative duration, blood loss, Harris hip score, incidence of
      complications, and radiological examinations. The time for fibular harvesting was
      20min on average. Total operative duration was 100-240min, with an average of
      150min. Blood loss averaged 300ml. All transplanted fibula integrated well to the
      femoral head 3.5years postoperatively with no severe complications observed. The
      results revealed that unilateral free vascularized fibula is effective for the
      treatment of bilateral osteonecrosis of the femoral head.

PMID- 23122875
TI  - Postoperative femoral component rotation and femoral anteversion after total knee
      arthroplasty in patients with distal femoral deformity.
AB  - We asked whether total knee arthroplasty (TKA) in patients with distal femoral
      deformity (DFD) would change femoral component rotation (FCR) and investigated
      the correlation between DFD and femoral anteversion (FA). 75 patients were
      divided into two groups according to the preoperative posterior condylar angle
      (PCA); group A without DFD (PCA<7 degrees ), group B with DFD (PCA>7 degrees ).
      We evaluated the different angles on the CT scan: (1) PCA, (2) angle between the
      line which is perpendicular to the Whiteside's line and PCL (WLP), and (3) FA.
      The mean FCRs were external rotation of 0.21 degrees +2.75 degrees  in group A
      and internal rotation of 4.48 degrees +2.51 degrees  in group B (P=0.001). The
      mean preoperative and postoperative FAs were similar in group A but were
      significantly different in group B (P=0.035). DFD resulted in excessive internal
      rotation of the femoral component. There was a secondary decrease in FA in
      patients with DFD. 

PMID- 23122876
TI  - Asymmetry of the leg alignment affects trunk bending in the coronal plane after
      unilateral total knee arthroplasty.
AB  - Unilateral total knee arthroplasty (TKA) would produce asymmetric changes of
      lower extremity in patients with bilateral varus deformity. Our purpose was to
      investigate whether asymmetry of the leg alignment would affect trunk bending in
      the coronal plane after unilateral TKA. Twenty patients (mean 76 years old) with
      bilateral end-stage knee osteoarthritis (OA) participated. Spine images during
      relaxed standing were obtained on pre- and postoperative day 21. As a result, the
      shoulder tilted more to the TKA side and the pelvis inclined more to the
      contralateral OA side. These results suggested that the trunk would bend away
      from the contralateral OA side after unilateral TKA in patients with bilateral
      end-stage knee OA and varus deformity. Asymmetry of the leg alignment led to
      asymmetric trunk bending.

PMID- 23122877
TI  - Posterior femoral condylar offset after total knee replacement in the risk of
      knee flexion contracture.
AB  - The aim of this study was to clarify the risk of knee flexion contracture
      associated with a posterior femoral condylar offset after total knee replacement
      (TKR). Radiographs from 100 healthy Japanese volunteers were included in the
      study. We evaluated femoral component posterior offset in various implants and
      compared them with the normal Japanese knee. Posterior offset of the femoral
      condyle is up to a maximum of 4.7 times greater than that of the healthy Japanese
      knee in all knee implants. Excess posterior offset of the femoral condyle in TKR
      prostheses may cause knee joint flexion contracture due to the relative
      shortening of the posterior soft tissue. 

PMID- 23122878
TI  - Impacts of ocean acidification on marine seafood.
AB  - Ocean acidification is a series of chemical reactions due to increased CO(2)
      emissions. The resulting lower pH impairs the senses of reef fishes and reduces
      their survival, and might similarly impact commercially targeted fishes that
      produce most of the seafood eaten by humans. Shelled molluscs will also be
      negatively affected, whereas cephalopods and crustaceans will remain largely
      unscathed. Habitat changes will reduce seafood production from coral reefs, but
      increase production from seagrass and seaweed. Overall effects of ocean
      acidification on primary productivity and, hence, on food webs will result in
      hard-to-predict winners and losers. Although adaptation, parental effects, and
      evolution can mitigate some effects of ocean acidification, future seafood
      platters will look rather different unless CO(2) emissions are curbed.

PMID- 23122880
TI  - Alterations in the cortical thickness and the amplitude of low-frequency
      fluctuation in patients with post-traumatic stress disorder.
AB  - The core neuropsychological processes underlying post-traumatic stress disorder
      (PTSD) have yet to be elucidated, and the association between anatomical and
      functional deficits in PTSD remains largely unknown. The aim of our study was to
      investigate the alterations in cortical thickness and amplitude of low-frequency
      fluctuation (ALFF) in PTSD patients resulting from motor vehicle accidents
      (MVCs), and to explore the association of cortical thickness and ALFF with the
      severity of PTSD symptoms. A total of 20 PTSD patients and 20 healthy controls
      were recruited and examined by high-resolution structural MRI combined with
      resting-state fMRI. The results showed significant decrease in cortical thickness
      in the left BA10, BA32 and BA45 and the right superior temporal gyrus in PTSD
      patients. The ALFF value in PTSD patients increased significantly in the left
      BA10 and BA32 and the right cerebellum. Linear regression revealed that decreased
      cortical thickness and increased ALFF in the BA10 were associated with the
      increased PTSD scores. These findings suggest that the structural integrity and
      resting-state function in the BA10 play an important role in the pathogenesis of
      PTSD.

PMID- 23122879
TI  - Hypocretinergic and non-hypocretinergic projections from the hypothalamus to the
      REM sleep executive area of the pons.
AB  - Within the postero-lateral hypothalamus neurons that utilize hypocretin or
      melanin-concentrating hormone (MCH) as neuromodulators are co-distributed. These
      neurons have been involved in the control of behavioral states, and a deficit in
      the hypocretinergic system is the pathogenic basis of narcolepsy with cataplexy.
      In this report, utilizing immunohistochemistry and retrograde tracing techniques,
      we examined the hypocretinergic innervation of the nucleus pontis oralis (NPO),
      which is the executive site that is responsible for the generation of REM sleep
      in the cat. The retrograde tracer cholera toxin subunit b (CTb) was administered
      in pontine regions where carbachol microinjections induced REM sleep. Utilizing
      immunohistochemical techniques, we found that approximately 1% of hypocretinergic
      neurons in the tuberal area of the hypothalamus project to the NPO. In addition,
      approximately 6% of all CTb+ neurons in this region were hypocretinergic. The
      hypocretinergic innervation of the NPO was also compared with the innervation of
      the same site by MCH-containing neurons. More than three times as many MCHergic
      neurons were found to project to the NPO compared with hypocretinergic cells;
      both neuronal types exhibited bilateral projections. We also identified a group
      of non-hypocretinergic non-MCHergic neuronal group of neurons that were
      intermingled with both hypocretinergic and MCHergic neurons that also projected
      to this same brainstem region. These neurons were grater in number that either
      hypocretin or MCH-containing neurons; their soma size was also smaller and their
      projections were mainly ipsilateral. The present anatomical data suggest that
      hypocretinergic, MCHergic and an unidentified companion group of neurons of the
      postero-lateral hypothalamus participate in the regulation of the neuronal
      activity of NPO neurons, and therefore, are likely to participate in the control
      of wakefulness and REM sleep.

PMID- 23122881
TI  - Effects of selective and non-selective cyclooxygenase inhibition against
      neurological deficit and brain oedema following closed head injury in mice.
AB  - The implication of cyclooxygenase (COX) type 2 in post-traumatic consequences is
      so far controversial. In experimental models of traumatic brain injury (TBI),
      genetic disruption or pharmacological inhibition of COX-2 has been shown to be
      neuroprotective, deleterious or without effect. Therefore, the aim of our study
      was to investigate the effect of COX-2 inhibition against neurological deficit
      and brain oedema after TBI that was induced by mechanical percussion in male
      Swiss mice. Despite the increased level and activity of COX-2, its inhibition
      either with nimesulide (12 mg/kg) or meloxicam (2mg/kg) modified neither the
      neurological score nor the brain water content that were evaluated at 6 and 24h
      after injury. Interestingly, the non-selective COX inhibition with indomethacin
      (5mg/kg) significantly promoted neurological recovery at 6 and 24h after trauma,
      without improving brain oedema. In conclusion, the present study yields
      considerable evidence that COX-2 may not solely constitute an interesting target
      for the treatment of TBI consequences. Our data point to a potentially
      deleterious role of COX-1 in the development of neurological impairment in brain
      injured mice. However, the neuroprotective mechanism of indomethacin remains to
      be clarified.

PMID- 23122882
TI  - Development of the Islands of Calleja.
AB  - The Islands of Calleja are aggregations of granule cells located in the basal
      forebrain of most vertebrate species. These cellular aggregations are typically
      classified as consisting of a single island, the insula magna located adjacent to
      the nucleus accumbens, and numerous small islands scattered among the dorsal
      aspect of the olfactory tubercle. While these structures have been widely
      described in adult, comparatively little is known about their development.
      Islands are first identifiable at P2-P4 with formation of the Insula Magna and
      several small aggregations in the caudolateral aspect of the basal forebrain. The
      Insula Magna fully forms at approximately P4, with continued formation of the
      small islands through P10 in a caudal to rostral gradient. Historically, there
      has been controversy as to whether neurons in the islands are GABAergic, due to
      limitations in resolving immunolabeling for GABA in the densely packed islands.
      We investigated the neurochemical identity of island cells by exploiting
      transgenic reporter mice expressing green fluorescent protein under the control
      of the GAD65 promoter. This demonstrated that the majority of neurons in the
      Islands of Calleja are GABAergic, primarily utilizing GAD65. Interestingly,
      several calcium binding protein expressing interneuron classes are present in the
      postnatal islands, but disappear with maturation. These findings show that the
      SVZ derived progenitors that migrate to the Islands of Calleja form different
      lineages to those destined for the olfactory bulbs, despite generation of both
      populations at the same age/location in the SVZ.

PMID- 23122883
TI  - Analysis of economic burden for patients with cystic echinococcosis in five
      hospitals in northwest China.
AB  - The direct and indirect economic burden of human cystic echinococcosis (CE) was
      investigated in the five specialist hydatid hospitals in Xinjiang, PR China, to
      provide information for health policy in the future. A total of 2018 CE patients
      (age range 2-88 years) attending the hospitals were studied between 2004 and
      2008. The per-person direct medical cost was US$1493.12 (95% CI 1438.43-1547.80)
      and the per-person direct non-medical cost was US$19.67. The indirect economic
      cost was US$1435.96 per person, and the disability-adjusted life-years (DALY)
      lost was approximately 1.03 DALY/person. This study is the first to combine the
      human capital method with DALYs to analyse the indirect CE economic burden in
      northwest China. Factors such as age, occupation and hospital level should be
      considered when developing polices to reduce the economic burden of CE.

PMID- 23122884
TI  - Enteric fever in Cambodian children is dominated by multidrug-resistant H58
      Salmonella enterica serovar Typhi with intermediate susceptibility to
      ciprofloxacin.
AB  - Infections with Salmonella enterica serovar Typhi isolates that are multidrug
      resistant (MDR: resistant to chloramphenicol, ampicillin, trimethoprim
      sulphamethoxazole) with intermediate ciprofloxacin susceptibility are widespread
      in Asia but there is little information from Cambodia. We studied invasive
      salmonellosis in children at a paediatric hospital in Siem Reap, Cambodia.
      Between 2007 and 2011 Salmonella was isolated from a blood culture in 162
      children. There were 151 children with enteric fever, including 148 serovar Typhi
      and three serovar Paratyphi A infections, and 11 children with a non-typhoidal
      Salmonella infection. Of the 148 serovar Typhi isolates 126 (85%) were MDR and
      133 (90%) had intermediate ciprofloxacin susceptibility. Inpatient antimicrobial
      treatment was ceftriaxone alone or initial ceftriaxone followed by a step-down to
      oral ciprofloxacin or azithromycin. Complications developed in 37/128 (29%)
      children admitted with enteric fever and two (1.6%) died. There was one confirmed
      relapse. In a sample of 102 serovar Typhi strains genotyped by investigation of a
      subset of single nucleotide polymorphisms, 98 (96%) were the H58 haplotype, the
      majority of which had the common serine to phenylalanine substitution at codon 83
      in the DNA gyrase. We conclude that antimicrobial-resistant enteric fever is
      common in Cambodian children and therapeutic options are limited.

PMID- 23122886
TI  - Integrated remodeling-to-fracture finite element model of human proximal femur
      behavior.
AB  - The purpose of this work was to develop an integrated remodeling-to-fracture
      finite element model allowing for the combined simulation of (i) simulation of a
      human proximal femur remodeling under a given boundary conditions, (ii) followed
      by the simulation of its fracture behavior (force-displacement curve and fracture
      pattern) under quasi-static load. The combination of remodeling and fracture
      simulation into one unified model consists in considering that the femur
      properties resulting from the remodeling simulation correspond to the initial
      state for the fracture prediction. The remodeling model is based on
      phenomenological one based on a coupled strain and fatigue damage stimulus. The
      fracture model is based on continuum damage mechanics in order to predict the
      progressive fracturing process which allows to predict the fracture pattern and
      the complete force-displacement curve under quasi-static load. To prevent mesh
      dependence that generally affects the damage propagation rate, regularization
      technique was applied in the current work. To investigate the potential of the
      proposed unified remodeling-to-fracture model, we performed remodeling
      simulations on a 3D proximal femur model for a duration of 365 days under five
      different daily loading conditions followed by a side fall fracture simulation
      reproducing previously published experimental tests (de Bakker et al. (2009),
      case C, male, 72 years old). We show here that the implementation of an
      integrated remodeling-to-fracture model provides more realistic prediction
      strategy to assess the bone remodeling effects on the fracture risk of bone.

PMID- 23122887
TI  - Synthesis and mechanical behavior of beta-tricalcium phosphate/titania composites
      addressed to regeneration of long bone segments.
AB  - Bioactive tricalcium phosphate/titania ceramic composites were synthesized by
      pressureless air sintering of mixed hydroxyapatite and titania (TiO2) powders.
      The sintering process was optimized to achieve dense ceramic bodies consisting in
      a bioactive/bioresorbable matrix (beta-tricalcium phosphate) reinforced with
      defined amounts of sub-micron sized titania particles. Extensive chemico-physical
      and mechanical characterization was carried out on the resulting composites,
      which displayed values of flexural strength, fracture toughness and elastic
      modulus in the range or above the typical ranges of values manifested by human
      cortical bone. It was shown that titania particles provided a toughening effect
      to the calcium-phosphate matrix and a reinforcement in fracture strength, in
      comparison with sintered hydroxyapatite bodies characterized by similar relative
      density. The characteristics of the resulting composites, i.e.
      bioactivity/bioresorbability and ability of manifesting biomimetic mechanical
      behavior, are features that can promote processes of bone regeneration in load
      bearing sites. Hence, in the perspective of developing porous bone scaffolds with
      high bioactivity and improved biomechanical behavior, TCP/TiO2 composites with
      controlled composition can be considered as very promising biomaterials for
      application in a field of orthopedics where no acceptable clinical solutions
      still exist.

PMID- 23122885
TI  - Use the force: membrane tension as an organizer of cell shape and motility.
AB  - Many cell phenomena that involve shape changes are affected by the intrinsic
      deformability of the plasma membrane (PM). Far from being a passive participant,
      the PM is now known to physically, as well as biochemically, influence cell
      processes ranging from vesicle trafficking to actin assembly. Here we review
      current understanding of how changes in PM tension regulate cell shape and
      movement, as well as how cells sense PM tension.

PMID- 23122888
TI  - Overall perceived health predicts risk of hospitalizations and death in adults
      with heart failure: a prospective longitudinal study.
AB  - BACKGROUND: Patient overall perception of health may provide an effective early
      warning for risk of hospitalization and death among heart failure patients.
      OBJECTIVE: Determine whether overall perceived health predicts all-cause
      hospitalization or death in heart failure patients after adjusting for
      confounding factors in a sample of adults with heart failure. DESIGN:
      Prospective, longitudinal, observational study. SETTINGS: Three outpatient urban
      settings in the northeast United States between 2007 and 2010. PARTICIPANTS:
      Adults with chronic Stage C heart failure confirmed by echocardiographic and
      clinical evidence. METHODS: A secondary analysis was conducted using data
      collected on 273 Stage C patients with heart failure. Participants in the parent
      study were followed for 6 months. Overall perceived health was measured by self
      report. Hospitalization and death were assessed from electronic hospital records
      and confirmed with county death records as needed. Cox proportional hazards
      models were used to examine the association between perceptions of health and
      rates of hospitalization and death. RESULTS: Patients with poor or fair perceived
      health had over 5.5 times the rate of death or hospitalization over the 6-month
      period (hazard ratio; 95% confidence interval: 2.0-15.6; p=0.001) after
      controlling for model covariates. The predictive ability of perceived health
      attenuated over time such that at 30-days patients who reported poor or fair
      perceived health had only 1.2 times the rate of an event and virtually no
      difference in event rate by 60-days. CONCLUSIONS: Overall perceived health is a
      powerful indicator of impending events and can be a quick tool for prioritizing
      heart failure patients who are at highest risk of imminent death and
      hospitalization. Questions about perceived health need to be asked of patients
      regularly in order to have clinical utility.

PMID- 23122889
TI  - Treatment and outcomes of patients with suspected acute coronary syndromes in
      relation to initial diagnostic impressions (insights from the Canadian Global
      Registry of Acute Coronary Events [GRACE] and Canadian Registry of Acute Coronary
      Events [CANRACE]).
AB  - The early diagnosis of acute coronary syndrome (ACS) remains challenging, and a
      considerable proportion of patients are diagnosed with "possible" ACS on
      admission. The Global Registry of Acute Coronary Events (GRACE/GRACE(2)) and
      Canadian Registry of Acute Coronary Events (CANRACE) enrolled 16,618 Canadian
      patients with suspected ACS in 1999 to 2008. We compared the demographic and
      clinical characteristics, use of cardiac procedures, prognostic accuracy of the
      GRACE risk score, and in-hospital outcomes between patients given an admission
      diagnosis of "definite" versus "possible" ACS by the treating physician. Overall,
      11,152 and 5,466 patients were given an initial diagnosis of "definite" ACS and
      "possible" ACS, respectively. Patients with a "possible" ACS had higher GRACE
      risk score (median 130 vs 125) and less frequently received aspirin, clopidogrel,
      heparin, or beta blockers within the first 24 hours of presentation and
      assessment of left ventricular function, stress testing, cardiac catheterization,
      and percutaneous coronary intervention (all p <0.05). Patients with "possible"
      ACS had greater rates of in-hospital myocardial infarction (9.0% vs 2.0%, p
      <0.05) and heart failure (12% vs 8.9%, p <0.05). The GRACE risk score
      demonstrated excellent discrimination for in-hospital mortality in both groups
      and for the entire study population. In conclusion, compared to patients with
      "definite" ACS on presentation, those with "possible" ACS had higher baseline
      GRACE risk scores but less frequently received evidence-based medical therapies
      within 24 hours of admission or underwent cardiac procedures during
      hospitalization. The GRACE risk score provided accurate risk assessment,
      regardless of the initial diagnostic impression.

PMID- 23122891
TI  - Brain injury as end-organ damage in hypertension.

PMID- 23122890
TI  - Cortisol secretion in depressed, and at-risk adults.
AB  - Distinct patterns of cortisol secretion have been associated with depression in
      past research, but it remains unclear whether individuals at-risk for depression
      may also have similar patterns of cortisol secretion. This is the first study to
      date of both naturalistic diurnal cortisol secretion and cortisol reactivity to a
      psychosocial laboratory stressor in depressed and at-risk adults. Cortisol
      secretion patterns were compared for 57 currently depressed, at-risk (based on
      trait-level positive and negative affect), and control participants over 5 days
      and in response to a laboratory stressor. After controlling for potentially
      confounding biobehavioral variables, the depressed group had a larger cortisol
      awakening response (CAR) and higher average diurnal cortisol compared to control
      participants. Individuals at-risk for depression also had significantly higher
      waking cortisol levels than control participants. Results for the psychosocial
      laboratory stressor did not show the predicted elevations in cortisol for
      depressed and at-risk participants compared to controls. The at-risk group
      recovered more quickly when compared to the depressed group both in levels of
      cortisol and concurrent measures of negative affect. The at-risk and depressed
      participants were similar on the diurnal cortisol measures, but differed on
      response to the laboratory social stressor, suggesting divergence in cortisol
      secretion patterns between currently depressed and temperamentally at-risk
      individuals. Further investigation of HPA functioning of individuals at-risk for
      depression may clarify the stress processes involved in risk for depression
      onset.

PMID- 23122893
TI  - Are facet joint bone marrow lesions and other facet joint features associated
      with low back pain? A pilot study.
AB  - OBJECTIVE: To determine the frequency of facet joint (FJ) bone marrow lesions,
      high FJ periarticular signal intensity, and FJ effusions in a convenience sample
      of patients with axial low back pain (LBP). DESIGN: A cross-sectional pilot study
      with retrospective data collection. SETTING: Outpatient spine clinics. PATIENTS:
      Sixty-four adults with axial LBP scheduled to receive an FJ intra-articular
      corticosteroid injection. METHODS: Clinical data were abstracted from the medical
      record by 1 physician, who was blinded to results of the magnetic resonance
      imaging evaluations. A musculoskeletal radiologist blinded to clinical
      information performed standardized assessments of the L1-S1 spinal levels for FJ
      bone marrow lesions, effusions, and high periarticular signal intensity on lumbar
      magnetic resonance imaging, including short tau inversion recovery sequences. We
      calculated the frequency of these FJ features and used generalized estimating
      equations to examine side-specific associations between the location of FJ
      features and the side on which LBP was experienced. RESULTS: The sample included
      64 participants with a mean (standard deviation) age of 59.9 +/- 14.5 years. FJ
      bone marrow lesions were present in 64.1%, effusions in 70.3%, and high
      periarticular signal intensity in 65.6% of participants. All the features were
      most common at the L4-L5 level. These FJ features showed significant associations
      with the side on which LBP was experienced or statistical trends toward an
      association, with or without adjustment for age, gender, and body mass index. The
      strongest side-specific associations were seen for the number of bone marrow
      lesions (odds ratio [OR] 1.60 [95% confidence interval {CI},1.05-2.43]), any FJ
      effusion (OR 2.23 [95% CI, 1.02-4.85]), and the number of joints with high
      periarticular signal intensity (OR 1.75 [95% CI, 1.16-2.63]). CONCLUSIONS: FJ
      bone marrow lesions, effusions, and high periarticular signal intensity were
      common in this sample of patients with axial LBP and substantially more frequent
      than in prior reports from unselected samples of patients with or without
      radicular pain. These FJ features demonstrate side-specific associations with
      LBP. Further study of associations between these FJ features and LBP are
      warranted.

PMID- 23122892
TI  - Effects of systolic blood pressure on white-matter integrity in young adults in
      the Framingham Heart Study: a cross-sectional study.
AB  - BACKGROUND: Previous studies have identified effects of age and vascular risk
      factors on brain injury in elderly individuals. We aimed to establish whether the
      effects of high blood pressure in the brain are evident as early as the fifth
      decade of life. METHODS: In an investigation of the third generation of the
      Framingham Heart Study, we approached all participants in 2009 to ask whether
      they would be willing to undergo MRI. Consenting patients underwent clinical
      assessment and cerebral MRI that included T1-weighted and diffusion tensor
      imaging to obtain estimates of fractional anisotropy, mean diffusivity, and grey
      matter volumes. All images were coregistered to a common minimum deformation
      template for voxel-based linear regressions relating fractional anisotropy, mean
      diffusivity, and grey-matter volumes to age and systolic blood pressure, with
      adjustment for potential confounders. FINDINGS: 579 (14.1%) of 4095 participants
      in the third-generation cohort (mean age 39.2 years, SD 8.4) underwent brain MRI
      between June, 2009 and June, 2010. Age was associated with decreased fractional
      anisotropy and increased mean diffusivity in almost all cerebral white-matter
      voxels. Age was also independently associated with reduced grey-matter volumes.
      Increased systolic blood pressure was linearly associated with decreased regional
      fractional anisotropy and increased mean diffusivity, especially in the anterior
      corpus callosum, the inferior fronto-occipital fasciculi, and the fibres that
      project from the thalamus to the superior frontal gyrus. It was also strongly
      associated with reduced grey-matter volumes, particularly in Brodmann's area 48
      on the medial surface of the temporal lobe and Brodmann's area 21 of the middle
      temporal gyrus. INTERPRETATION: Our results suggest that subtle vascular brain
      injury develops insidiously during life, with discernible effects even in young
      adults. These findings emphasise the need for early and optimum control of blood
      pressure. FUNDING: National Institutes of Health and National Heart, Lung, and
      Blood Institute; National Institute on Aging; and National Institute of
      Neurological Disorders and Stroke.

PMID- 23122894
TI  - Daily treatment time and functional gains of stroke patients during inpatient
      rehabilitation.
AB  - OBJECTIVE: To study the effects of daily treatment time on functional gain of
      patients who have had a stroke. DESIGN: A retrospective cohort study. SETTING: An
      inpatient rehabilitation hospital (IRH) in northern California. PARTICIPANTS:
      Three hundred sixty patients who had a stroke and were discharged from the IRH in
      2007. INTERVENTIONS: Average minutes of rehabilitation therapy per day, including
      physical therapy, occupation therapy, speech and language therapy, and total
      treatment. MAIN OUTCOME MEASURES: Functional gain measured by the Functional
      Independence Measure, including activities of daily living, mobility, cognition,
      and the total of the Functional Independence Measure (FIM) scores. RESULTS: The
      study sample had a mean age of 64.8 years; 57.4% were men and 61.4% were white.
      The mean total daily therapy time was 190.3 minutes, and the mean total
      functional gain was 26.0. A longer daily therapeutic duration was significantly
      associated with total functional gain (r = .23, P = .0094). Patients who received
      a total therapy time of <3.0 hours per day had significantly lower total
      functional gain than did those treated >=3.0 hours. No significant difference in
      total functional gain was found between patients treated >=3.0 but <3.5 hours and
      >=3.5 hours per day. The daily treatment time of physical therapy, occupational
      therapy, and speech and language therapy also was significantly associated with
      corresponding subscale functional gains. In addition, hemorrhagic stroke, left
      brain injury, earlier IRH admission, and a longer IRH stay were associated with
      total functional improvement. CONCLUSIONS: The study demonstrated a significant
      relationship between daily therapeutic duration and functional gain during IRH
      stay and showed treatment time thresholds for optimal functional outcomes for
      patients in inpatient rehabilitation who had a stroke.

PMID- 23122895
TI  - Assessment of pelvic floor muscle pressure in female athletes.
AB  - OBJECTIVE: To evaluate the pressure of the pelvic floor muscles in female
      athletes and the associated signs and symptoms of stress urinary incontinence.
      DESIGN: A prospective observational study. SETTING: An academic institution,
      primary level of clinical care. PARTICIPANTS: Forty women between 18 and 30 years
      of age divided into 4 groups: 10 volleyball players, 10 handball players, 10
      basketball players, and 10 nonathletes. METHODS: The measurement of intracavity
      pressure was performed with use of a perineometer. The volunteers were instructed
      to perform 3 maximum isometric contractions of the perineum, held for 4 seconds.
      Data regarding specific training and urinary symptoms were collected through a
      questionnaire. MAIN OUTCOME MEASUREMENTS: Statistical analysis was performed by
      analysis of variance, with a significance level of 5%. The Spearman correlation
      was used to verify the degree of association between variables related to
      training, urinary symptoms, and perineal pressure. RESULTS: The average (standard
      deviation) perineal pressure for nonathletes was 6.73 +/- 1.91 mm Hg. The average
      perineal pressure for handball players was 5.55 +/- 1.43 mm Hg; for volleyball
      players, 4.36 +/- 1.43 mm Hg; and for basketball players, 3.65 +/- 1.35 mm Hg.
      Statistically significant differences were found in the perineal pressure of
      volleyball (P = .009) and basketball players (P = .039) compared with
      nonathletes. The number of games per year, strength training, and on-court
      workout correlated significantly with perineal pressure (Spearman correlation
      coefficient [Rs] of -0.512 for the 3 variables). Urine leakage through effort and
      nocturia correlated moderately with perineal pressure (Rs of -0.51 and -0.54,
      respectively). A strong correlation was found between urinary frequency and
      perineal pressure (Rs of -0.85). CONCLUSIONS: Analysis of these data suggests
      that perineal pressure is decreased in female athletes compared with nonathlete
      women. A lower perineal pressure correlates with increased symptoms of urinary
      incontinence and pelvic floor dysfunction.

PMID- 23122896
TI  - Reading performance after vision rehabilitation of subjects with homonymous
      visual field defects.
AB  - OBJECTIVE: To examine whether increased visual functioning after vision
      restoration training (VRT) coincides with improved reading abilities. DESIGN:
      Prospective noncontrolled open-label trial. SETTING: Controlled laboratory
      setting for all diagnostic procedures that were conducted before and after 6
      months of home-based VRT with telemedicine support. PATIENTS: Eleven subjects who
      had experienced a posterior-parietal stroke and have homonymous visual field
      defects. INTERVENTIONS: Six months of VRT (1 hour daily repeated light
      stimulation in the partially damaged visual field). MAIN OUTCOME MEASUREMENTS:
      VRT outcome measures were the number of detected light stimuli in eye-tracker
      controlled high-resolution perimetry and the spared visual field within the
      affected hemifield up to the relative and absolute defect visual field border
      (square degrees). Enlargements of spared visual field within the affected
      hemifield were correlated with changes of reading speed after VRT. RESULTS: After
      VRT, the number of detected light stimuli increased by 5.02 +/- 4.31% (mean +/-
      SD; P = .03). The spared visual field up to the relative defect visual field
      border increased from 18.09 +/- 32.35 square degrees before to 137.40 +/- 53.32
      after VRT (P = .006), as well as for the absolute defect visual field border from
      36.95 +/- 33.77 square degrees before VRT to 152.02 +/- 49.70 after VRT (P =
      .005). Reading speed increased from 108.95 +/- 33.95 words per minute before VRT
      to 122.26 +/- 30.35 after VRT (P = .017), which significantly correlated with
      increased spared visual field up to the relative defect visual field border (r =
      0.73, P = .016). Measures of eye movement variability did not correlate with VRT
      outcome. CONCLUSIONS: VRT improved visual fields in parafoveal areas, which are
      most relevant for reading. This finding cannot be explained by changes in eye
      movement behavior. Because of a significant association between improvements of
      parafoveal vision and reading speed, we propose that patients with homonymous
      visual field defects who have reading deficits may benefit from visual
      stimulation by training.

PMID- 23122897
TI  - Alterations in gait speed and age do not fully explain the changes in gait
      mechanics associated with healthy older women.
AB  - Older adults exhibit modified gait patterns compared to the young, adopting
      movement strategies in response to changes in musculoskeletal function.
      Investigating the functional mobility of older women is particularly important
      because of their increased life expectancy and greater falls risk compared to
      men. We explored the relationships between gait parameters and age in healthy
      older women whilst accounting for declining gait speeds. Kinematic and kinetic
      data were collected from thirty-nine women (60-83 years) whilst walking at a
      comfortable cadence. Regression analysis assessed the capacity of gait speed and
      age to explain the variance in gait associated with older age. Speed explained
      the majority of variance in many gait parameters. By including age in the
      regression, the total explained variance (R2) for foot clearance (70%), ankle
      plantarflexion angle (30%), peak ankle plantarflexor moment (58%), and hip power
      generation (56%) were significantly (p<0.05) greater than for speed alone.
      Nonetheless, changes in speed and age did not fully explain the variance in gait
      mechanics associated with older age and other contributing factors must exist.
      Losses of 1.2%/year in gait speed were predicted by age, exceeding previous
      predictions of -0.7%/year. Furthermore, the accumulation of apparently small
      decreases of 0.2 cm/year in peak foot-to-ground clearance has clinical
      implications and offers insight into the mechanisms by which gait becomes
      hazardous in older age.

PMID- 23122898
TI  - Measuring movement fluency during the sit-to-walk task.
AB  - BACKGROUND: Restoring movement fluency is a key focus for physical
      rehabilitation; it's measurement, however, lacks objectivity. The purpose of this
      study was to find whether measurable movement fluency variables differed between
      groups of adults with different movement abilities whilst performing the sit-to
      walk (STW) movement. The movement fluency variables were: (1) hesitation during
      movement (reduction in forward velocity of the centre of mass; CoM), (2)
      coordination (percentage of temporal overlap of joint rotations) and (3)
      smoothness (number of inflections in the CoM jerk signal). METHODS: Kinematic
      data previously collected for another study were extracted for three groups:
      older adults (n=18), older adults at risk of falling (OARF, n=18), and younger
      adults (n=20). Each subject performed the STW movement freely while a motion
      analysis system tracked 11 body segments. The fluency variables were derived from
      the processed kinematic data and tested for group variation using analysis of
      variance. FINDINGS: All three variables showed statistically significant
      differences among the groups. Hesitation (F=15.11, p<0.001) was greatest in the
      OARF 47.5% (SD 18.0), compared to older adults 30.3% (SD 15.9) and younger adults
      20.8% (SD 11.4). Co-ordination (F=44.88, p<0.001) was lowest for the OARF (6.93%,
      SD 10.99) compared to both the young (31.21%, SD 5.48) and old (26.24%, SD 5.84).
      Smoothness (F=35.96, p<0.001) was best in the younger adults, 18.3 (SD 5.2)
      inflections, compared to the old, 42.5 (SD 11.5) and OARF, 44.25 (SD 7.29).
      INTERPRETATION: Hesitation, co-ordination and smoothness may be valid indicators
      of movement fluency in adults, with important consequences for research and
      clinical practice.

PMID- 23122899
TI  - It's not your grandfather's field plasma.
AB  - Initiating prehospital resuscitation with plasma in patients with trauma
      associated hemorrhagic shock will result in more rapid and durable clot formation
      and, thus, the need for fewer packed cell infusions, less frequent use of
      cryoprecipitate, and more ventilator-free hospital days compared with those of
      patients randomized to standard crystalloid field resuscitation.

PMID- 23122900
TI  - Biliopancreatic diversion with transient gastroplasty and duodenal switch: long
      term results of a multicentric study.
AB  - BACKGROUND: Over the years, several modifications of the Scopinaro
      biliopancreatic diversion (BPD) have been proposed. This retrospective study
      reported the results of 15 years of follow-up after open BPD coupled with a type
      of transient gastroplasty (TG) and duodenal switch (DS), termed BPD-TG with DS.
      METHODS: Data were analyzed for 874 patients operated on between January 1993 and
      May 2010 in 3 different surgical departments. RESULTS: The median preoperative
      body mass index (BMI) was 52 kg/m2 (range, 35-63). Comorbidities present were
      hypertension (57%), hypercholesterolemia (87%), hypertriglyceridemia (53%), type
      2 diabetes (35%), and obstructive sleep apnea syndrome (OSAS; 9%). The mean
      follow-up was 11.9 +/- 3.1 years. The median BMI decreased to 33.9 after 1 year
      from bariatric surgery, 31.1 after 2-5 years, 30.9 after 5-10 years, and 31.2
      kg/m2 after 10-15 years. Overall, 67% of diabetic patients were able to stop
      insulin and 97% were able to stop oral hypoglycemic drugs within 1 year. Blood
      pressure, triglyceride levels, and cholesterol levels became normal in >96% of
      patients within 1 year. OSAS was resolved within 8 months in all cases. One year
      postoperatively, but absent thereafter, we observed severe hypoalbuminemia (serum
      albumin <3 g/dL) in 1.7% of patients and severe iron-deficiency anemia in 1.9%.
      Incisional hernias were recorded in 30% and anastomotic ulcers in 2.4% of cases.
      Mortality was null. CONCLUSION: Our results suggest considering BPD-TG with DS as
      a viable bariatric operation, with its excellent long-term outcome in terms of
      weight loss, improvement of obesity-related diseases, and quality of life.

PMID- 23122901
TI  - Linkage of a clinical surgical registry with Medicare inpatient claims data using
      indirect identifiers.
AB  - BACKGROUND: A variety of data sources are available for measuring the quality of
      health care. Linking records from different sources can create unique and
      powerful databases that can be used to evaluate clinically relevant questions and
      direct health care policy. The objective of this study was to develop and
      validate a deterministic linkage algorithm that uses indirect patient identifiers
      to reliably match records from a surgical clinical registry with Medicare
      inpatient claims data. METHODS: Patient records from the American College of
      Surgeons National Surgical Quality Improvement Program (ACS-NSQIP), years 2005
      2008, were linked to claims data in the Medicare Provider Analysis and Review
      file (MedPAR) by the use of a deterministic linkage algorithm and the following
      indirect patient identifiers: hospital, age, sex, diagnosis, procedure and dates
      of admission, discharge, and procedure. We validated the linkage procedure by
      systematically reviewing subsets of matched and unmatched records and by
      determining agreement on patient-level coding of inpatient mortality. RESULTS: Of
      the 150,454 records in ACS-NSQIP eligible for matching, 80.5% were linked to a
      MedPAR record. This percentage is within the expected match range given the
      estimated percentage of ACS-NSQIP patients likely to be Medicare beneficiaries.
      Systematic checks revealed no evidence of bias in the linkage procedure and there
      was excellent agreement on patient-level coding of mortality (kappa 0.969). The
      final linked database contained 121,070 patient records from 217 hospitals.
      CONCLUSION: This study demonstrates the feasibility and validity of a method for
      linking 2 data sources without direct personal identifiers. As clinical
      registries and other data sources continue to proliferate, linkage algorithms
      such as described here will be critical for quality measurement purposes.

PMID- 23122902
TI  - Peer review and psychiatric physician fitness for duty evaluations: analyzing the
      past and forecasting the future.
AB  - In the United States, oversight of health care practitioners is delegated to a
      matrix of health care entities including but not limited to the state medical
      board which licenses physicians in the relevant jurisdiction. Typically, these
      organizations have their own codes of professional conduct. When a physician
      joins one of these health care organizations, legally the physician has entered
      into a contract with the organization and agreed to be bound by its regulations
      and procedures. The organization's peer review of a member physician for reasons
      of investigating questions of health care quality may require a psychiatric
      fitness for duty evaluation. That assessment is a forensic psychiatric
      examination to assist the peer review body much as an expert witness would assist
      the trier of fact in a criminal or civil law adjudication. Experts can better
      perform these functions if they are familiar with the legal differences that
      define these agencies' service under administrative as compared to civil or
      criminal law and procedures.

PMID- 23122903
TI  - Assessing recent adolescent sexual risk using a sexual health history calendar:
      results from a mixed method feasibility study.

PMID- 23122905
TI  - Negotiating uncertainty: the transitional process of adapting to life with HIV.
AB  - Glaser's (1978) grounded-theory method was used to investigate the transitional
      process of adapting to life with HIV. Semistructured interviews took place with 8
      male HIV-infected participants recruited from a clinic in South Wales, United
      Kingdom. Data analysis used open, substantive, and theoretical coding. Adapting
      to a life with HIV infection emerged as a process of adapting to uncertainty with
      "negotiating uncertainty" as a core concept. Seven subcategories represented
      movements between bipolar opposites labeled "anticipating hopelessness" and
      "regaining optimism." This work progresses the theoretical concepts of
      transitions, uncertainty, and adaptation in relation to the HIV experience.

PMID- 23122904
TI  - Medication-taking self-efficacy and medication adherence among HIV-infected
      cocaine users.
AB  - This prospective, observational study tested the ability of self-efficacy for
      taking antiretroviral medications to predict medication adherence among current
      and former cocaine and heroin users. Electronic monitors to record bottle
      openings and self-report measures of medication adherence were used. The sample
      included 99 men and women who were interviewed at 4-week intervals for 6 months.
      Mixed effects regression models to test the relationship of substance use and
      self-efficacy for medication-taking with percent of self-report adherence, dose
      adherence, number of days adherent, and adherence to medication schedule at each
      study visit showed that medication-taking self-efficacy was significantly related
      to all measures of adherence except schedule adherence. Findings also showed that
      electronically monitored adherence measures declined over the study period
      whereas self-report adherence did not. Findings suggest that self-efficacy can
      have a sustained effect on adherence to doses but may not be an influential
      predictor of adherence to their correct timing.

PMID- 23122906
TI  - Use of complementary and alternative medicines and supplements by Mexican-origin
      patients in a U.S.-Mexico border HIV clinic.
AB  - This article draws from a study investigating the influence of institutional and
      psychosocial factors on adherence to antiretroviral (ARV) medications by Mexican
      origin persons living with HIV (PWLH) on the U.S.-Mexico border and seeking
      treatment at a clinic in El Paso, Texas. Among 113 participants, many individuals
      reported using complementary and alternative medicines (CAM) to support general
      health and their immune systems and to address symptoms of HIV-related diseases
      and ARV side effects. CAM were seen as complementing ARV treatment; however, CAM
      use was often not reported to health care providers out of concern about
      disapproval and loss of care privileges. This finding challenges researchers and
      providers to consider seriously how Hispanic populations, with their CAM use, may
      exhibit the hybridization of health and healing. Information on CAM use needs to
      be available to providers to assess the benefits and contraindications of use and
      to develop realistic and effective care strategies. 

PMID- 23122907
TI  - Text-messaging-enhanced HIV intervention for African American adolescents: a
      feasibility study.
AB  - We examined the feasibility and acceptability of an HIV prevention intervention
      for African American adolescents delivered via mobile cell phones and looked at
      intervention-related changes in beliefs and sexual behaviors. We used a
      longitudinal one-group comparison design with data collected at three points.
      Forty adolescents, 13-18 years old, participated in the Becoming a Responsible
      Teen intervention followed by the delivery of daily multimedia messages for 3
      months. The mobile-cell-phone enhanced intervention was feasible and acceptable
      to the participants. Greater HIV knowledge, improved attitudes toward condoms,
      and increased perceived HIV risk scores were observed with older adolescents (16
      18 years old). Behavior trends showed a decrease in the number of times
      participants reported engaging in unprotected sexual intercourse over the
      previous 2 months. Mobile-cell-phone multimedia-text-messaging boosters tested in
      this study provided preliminary evidence of efficacy of the enhanced HIV
      prevention intervention for African American youth.

PMID- 23122908
TI  - Review of current conceptual models and frameworks to guide transitions of care
      in older adults.
AB  - Older adults are at high risk for gaps in care as they move between health care
      providers and settings during the course of illness, such as following hospital
      discharge. These gaps in care may result in unnecessary re-hospitalization and
      even death. Nurses can assist older adults to achieve successful transitions of
      care by taking a systematic approach and individualizing care to meet patient and
      family health literacy, cognitive, and sensory needs. This article reviews trends
      in transitions of care, models, partnerships, and health literacy. Models
      described include the Transitional Care Model, Care Transitions Program, Project
      BOOST (Better Outcomes for Older adults through Safe Transitions), Project RED
      (Re-engineered Discharge), Chronic Care Model, and INTERACT(II) (Interventions to
      Reduce Acute Care Transfers). Approaches to transitions of care are discussed,
      and resources for geriatric nurses are provided.

PMID- 23122909
TI  - Antidepressant adverse drug reactions in older adults: implications for RNs and
      APNs.
AB  - The purpose of this article is to review essential information about the
      pharmacokinetics of antidepressants in older adults and possible adverse drug
      reactions associated with each antidepressant class to avoid or minimize adverse
      drug events.

PMID- 23122910
TI  - Outcomes of laparoscopic colorectal surgery: data from the Nationwide Inpatient
      Sample 2009.
AB  - BACKGROUND: Specific International Classification of Diseases, Ninth Revision,
      codes for laparoscopic procedures introduced in 2008 allow a more accurate
      evaluation of laparoscopic colorectal surgery. METHODS: Using the Nationwide
      Inpatient Sample 2009, a retrospective analysis of surgical colorectal cancer and
      diverticulitis patients was conducted. Logistic regression was used to estimate
      odds ratios comparing the outcomes of laparoscopic, open, and converted surgery.
      RESULTS: A total of 121,910 patients underwent resection for cancer and
      diverticulitis, 35.41% of whom underwent laparoscopic surgery. Compared with open
      surgery, laparoscopic surgery had lower postoperative complication rates, lower
      mortality, shorter hospital stays, and lower costs. Compared to open surgery,
      laparoscopic surgery independently decreased mortality, postoperative anastomotic
      leak, urinary tract infection, ileus or obstruction, pneumonia, respiratory
      failure, and wound infection. Converted surgery was independently associated with
      anastomotic leak, wound infection, ileus or obstruction, and urinary tract
      infection. CONCLUSIONS: Laparoscopic colorectal surgery has lower postoperative
      complications, lower mortality, lower costs, and shorter hospital stays.
      Conversion had higher complications compared with laparoscopy. The use of
      laparoscopy should increase with efforts to minimize conversion.

PMID- 23122911
TI  - A retrospective comparison of water birth and conventional vaginal birth among
      women deemed to be low risk in a secondary level hospital in Australia.
AB  - BACKGROUND: Water birth involves the complete birth of the baby under warm water.
      There is a lack of consensus regarding the safety of water birth. AIM: This study
      aimed to describe the maternal and neonatal outcomes associated with water birth
      among labouring women deemed at low risk for obstetric complications and compare
      these outcomes against women of similar risk who had a standard land birth.
      METHOD: A retrospective audit and comparison of women giving birth in water with
      a matched cohort who birthed on land at Bankstown hospital over a 10 year period
      (2000-2009). RESULTS: In total 438 childbearing women were selected for this
      study (N=219 in each arm). Primigravida women represented 42% of the study
      population. There was no significant difference in mean duration of both first
      and second stages of labour or postpartum blood loss between the two birth
      groups. There were no episiotomies performed in the water birth arm which was
      significantly different to the comparison group (N=33, p<0.001). There were more
      babies in the water birth group with an Apgar score of 7 or less at 1min
      (compared to land births). However, at 5min there was no difference in Apgar
      scores between the groups. Three of eight special care nursery admissions in the
      water birth group were related to feeding difficulties. CONCLUSION: This is the
      largest study on water birth in an Australian setting. Despite the limitations of
      a retrospective audit the findings make a contribution to the growing body of
      knowledge on water birth.

PMID- 23122912
TI  - Increased expression of fatty acid binding protein 4 and leptin in resident
      macrophages characterises atherosclerotic plaque rupture.
AB  - OBJECTIVE: Resident macrophages play an important role in atheromatous plaque
      rupture. The macrophage gene expression signature associated with plaque rupture
      is incompletely defined due to the complex cellular heterogeneity in the plaque.
      We aimed to characterise differential gene expression in resident plaque
      macrophages from ruptured and stable human atheromatous lesions. METHODS AND
      RESULTS: We performed genome-wide expression analyses of isolated macrophage-rich
      regions of stable and ruptured human atherosclerotic plaques. Plaques present in
      carotid endarterectomy specimens were designated as stable or ruptured using
      clinical, radiological and histopathological criteria. Macrophage-rich regions
      were excised from 5 ruptured and 6 stable plaques by laser micro-dissection.
      Transcriptional profiling was performed using Affymetrix microarrays. The
      profiles were characteristic of activated macrophages. At a false discovery rate
      of 10%, 914 genes were differentially expressed between stable and ruptured
      plaques. The findings were confirmed in fourteen further stable and ruptured
      samples for a subset of eleven genes with the highest expression differences (p <
      0.05). Pathway analysis revealed that components of the PPAR/Adipocytokine
      signaling pathway were the most significantly upregulated in ruptured compared to
      stable plaques (p = 5.4 * 10(-7)). Two key components of the pathway, fatty-acid
      binding-protein 4 (FABP4) and leptin, showed nine-fold (p = 0.0086) and five-fold
      (p = 0.0012) greater expression respectively in macrophages from ruptured
      plaques. CONCLUSIONS: We found differences in gene expression signatures between
      macrophages isolated from stable and ruptured human atheromatous plaques. Our
      findings indicate the involvement of FABP4 and leptin in the progression of
      atherosclerosis and plaque rupture, and suggest that down-regulation of
      PPAR/adipocytokine signaling within plaques may have therapeutic potential.

PMID- 23122913
TI  - Diagnostic performance of fluorodeoxyglucose-positron emission
      tomography/computed tomography combined with ultrasonography-guided fine needle
      aspiration cytology for identifying axillary lymph node status in patients with
      breast cancer.
AB  - AIM: The aim of this study was to assess the diagnostic performance of
      fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT)
      in combination with ultrasonography-guided fine needle aspiration cytology (US
      guided FNAC) for the preoperative diagnosis of axillary lymph node (ALN)
      metastases in patients with breast cancer. MATERIALS AND METHODS: A total of 318
      patients with breast cancer were recruited retrospectively. Some of the cases
      that underwent neoadjuvant chemotherapy (NAC) were included. The sensitivity and
      specificity of FDG-PET/CT were calculated. We assessed the relationship between
      the combined results for US-guided FNAC with FDG-PET/CT and the pathological ALN
      status. RESULTS: A total of 271 patients underwent FDG-PET/CT. Of these patients,
      41 underwent US-guided FNAC. The sensitivity and the specificity of FDG-PET/CT
      for the cases without NAC were 18.5%, 97.1%, respectively. The sensitivity in
      cases with NAC was 68.2%. As a whole, the sensitivity was 40.8%. ALN metastasis
      was detected using US-guided FNAC in a case with a negative FDG uptake in the
      ALN. The T stage was T2 in the case and the FDG uptake at the primary site was
      poor. CONCLUSION: FDG-PET/CT has a good specificity for ALN metastasis, although
      its sensitivity is limited, especially in early-stage cases. In cases with a
      negative FDG uptake in the ALN, US-guided FNAC may play a role in the detection
      of lymph node metastasis when the primary tumor size is large and the FDG uptake
      in the primary tumor is low.

PMID- 23122914
TI  - Phytosiderophore release by wheat genotypes differing in zinc deficiency
      tolerance grown with Zn-free nutrient solution as affected by salinity.
AB  - There is limited information concerning the effect of salinity on
      phytosiderophores exudation from wheat roots. The aim of this hydroponic
      experiment was to investigate the effect of salinity on phytosiderophore release
      by roots of three bread wheat genotypes differing in Zn efficiency (Triticum
      aestivum L. cvs. Rushan, Kavir, and Cross) under Zn deficiency conditions. Wheat
      seedlings were transferred to Zn-free nutrient solutions and exposed to three
      salinity levels (0, 60, and 120 mM NaCl). The results indicated that Cross and
      Rushan genotypes exuded more phytosiderophore than did the Kavir genotype. Our
      findings suggest that the adaptive capacity of Zn-efficient 'Cross' and 'Rushan'
      wheat genotypes to Zn deficiency is due partly to the higher amounts of
      phytosiderophore release. Only 15 days of Zn deficiency stress was sufficient to
      distinguish between Zn-efficient (Rushan and Cross) and Zn-inefficient (Kavir)
      genotypes, with the former genotypes exuding more phytosiderophore than the
      latter. Higher phytosiderophore exudation under Zn deficiency conditions was
      accompanied by greater Fe transport from root to shoot. The maximum amount of
      phytosiderophore was exuded at the third week in 'Cross' and at the fourth week
      in 'Kavir' and 'Rushan'. For all three wheat genotypes, salinity stress resulted
      in higher amounts of phytosiderophore exuded by the roots. In general, for
      'Kavir', the largest amount of phytosiderophore was exuded from the roots at the
      highest salinity level (120mM NaCl), while for 'Cross' and 'Rushan', no
      significant difference was found in phytosiderophore exudation between the 60 and
      120 mM NaCl treatments. More investigation is needed to fully understand the
      physiology of elevated phytosiderophore release by Zn-deficient wheat plants
      under salinity conditions.

PMID- 23122915
TI  - Repetitive deep transcranial magnetic stimulation improves verbal fluency and
      written language in a patient with primary progressive aphasia-logopenic variant
      (LPPA).
AB  - BACKGROUND: To date, no therapies are available for the logopenic variant of
      primary progressive aphasia (LPPA). Even though deep repetitive transcranial
      magnetic stimulation (rTMS) may improve cognitive functions in some
      neurodegenerative disorders, no previous studies investigated its effects in
      patients with LPPA. OBJECTIVE: Our aim was to investigate the effects on
      cognitive function of high frequency rTMS (hf-rTMS) delivered over the left dorso
      lateral prefrontal cortex (DLPFC) through a coil designed for deep rTMS, compared
      to a SHAM stimulation, in a right-handed patient with LPPA. METHODS: The patient
      presented a progressive language impairment (phonological errors in speech and
      naming, impaired single word retrieval and sentences repetition) and predominant
      left perisylvian atrophy and hypoperfusion. He received four stimulation cycles
      (two REAL and two SHAM) each of whom lasted 20 min for 5 consecutive days.
      Patient's performances in frontal, visuo-spatial and linguistic tasks were
      evaluated before and after each stimulation session. Test scores after REAL were
      compared with those obtained at baseline and after SHAM. RESULTS: We found a
      temporary and highly significant improvement in the linguistic skills (both oral
      and written tasks) but not in the other cognitive domains tested, after REAL, but
      not SHAM stimulations. DISCUSSION: Hf-rTMS delivered over the DLPFC could improve
      language in LPPA by enhancing long-term potentiation and synaptic plasticity
      within the stimulated and interconnected areas involved in language network. Our
      findings might prompt future researches into the feasibility and efficacy of deep
      hf-rTMS as a therapeutic tool in progressive aphasia syndromes and other
      neurodegenerative disorders.

PMID- 23122916
TI  - Vagus nerve stimulation therapy randomized to different amounts of electrical
      charge for treatment-resistant depression: acute and chronic effects.
AB  - BACKGROUND: Major depressive disorder is a prevalent, disabling, and often
      chronic or recurrent psychiatric condition. About 35% of patients fail to respond
      to conventional treatment approaches and are considered to have treatment
      resistant depression (TRD). OBJECTIVE: We compared the safety and effectiveness
      of different stimulation levels of adjunctive vagus nerve stimulation (VNS)
      therapy for the treatment of TRD. METHODS: In a multicenter, double blind study,
      331 patients with TRD were randomized to one of three dose groups: LOW (0.25 mA
      current, 130 MUs pulse width), MEDIUM (0.5-1.0 mA, 250 MUs), or HIGH (1.25-1.5
      mA, 250 MUs). A highly treatment-resistant population (>97% had failed to respond
      to >=6 previous treatments) was enrolled. Response and adverse effects were
      assessed for 22 weeks (end of acute phase), after which output current could be
      increased, if clinically warranted. Assessments then continued until Week 50 (end
      of long-term phase). RESULTS: VNS therapy was well tolerated. During the acute
      phase, all groups showed statistically significant improvement on the primary
      efficacy endpoint (change in Inventory of Depressive Symptomatology-Clinician
      Administered Version [IDS-C]), but not for any between-treatment group
      comparisons. In the long-term phase, mean change in IDS-C scores showed continued
      improvement. Post-hoc analyses demonstrated a statistically significant
      correlation between total charge delivered per day and decreasing depressive
      symptoms; and analysis of acute phase responders demonstrated significantly
      greater durability of response at MEDIUM and HIGH doses than at the LOW dose.
      CONCLUSIONS: TRD patients who received adjunctive VNS showed significant
      improvement at study endpoint compared with baseline, and the effect was durable
      over 1 year. Higher electrical dose parameters were associated with response
      durability.

PMID- 23122917
TI  - Cerebellar transcranial direct current stimulation modulates verbal working
      memory.
AB  - BACKGROUND: Neuroimaging studies show cerebellar activations in a wide range of
      cognitive tasks and patients with cerebellar lesions often present cognitive
      deficits suggesting a cerebellar role in higher-order cognition. OBJECTIVE: We
      used cathodal transcranial direct current stimulation (tDCS), known to inhibit
      neuronal excitability, over the cerebellum to investigate if cathodal tDCS
      impairs verbal working memory, an important higher-order cognitive faculty.
      METHOD: We tested verbal working memory as measured by forward and backward digit
      spans in 40 healthy young participants before and after applying cathodal tDCS (2
      mA, stimulation duration 25 min) to the right cerebellum using a randomized, sham
      controlled, double-blind, cross-over design. In addition, we tested the effect of
      cerebellar tDCS on word reading, finger tapping and a visually cued sensorimotor
      task. RESULTS: In line with lower digit spans in patients with cerebellar
      lesions, cerebellar tDCS reduced forward digit spans and blocked the practice
      dependent increase in backward digit spans. No effects of tDCS on word reading,
      finger tapping or the visually cued sensorimotor task were found. CONCLUSION: Our
      results support the view that the cerebellum contributes to verbal working memory
      as measured by forward and backward digit spans. Moreover, the induction of
      reversible "virtual cerebellar lesions" in healthy individuals by means of tDCS
      may improve our understanding of the mechanistic basis of verbal working memory
      deficits in patients with cerebellar lesions.

PMID- 23122918
TI  - Transcranial direct current stimulation ameliorates tactile sensory deficit in
      multiple sclerosis.
AB  - BACKGROUND: Deficit of tactile sensation in patients with MS is frequent and can
      be associated with interference with daily life activities. Transcranial direct
      current stimulation (tDCS) showed to increase tactile discrimination in healthy
      subjects. OBJECTIVE: In the present study, we investigated whether tDCS may be
      effective in ameliorating tactile sensory deficit in MS patients. METHODS:
      Patients received sham or real anodal tDCS of the somatosensory cortex for 5
      consecutive days in a randomized, double blind, sham-controlled study.
      Discrimination thresholds of spatial tactile sensation were measured using the
      grating orientation task (GOT). As secondary outcomes we also measured subjective
      perception of tactile sensory deficit through a visual analog scale (VAS),
      quality of life and overall disability to evaluate the impact of the treatment on
      patients daily life. Evaluations were performed at baseline and during a 4-week
      follow-up period. RESULTS: Following anodal but not sham tDCS over the
      somatosensory cortex, there was a significant improvement of discriminatory
      thresholds at the GOT and increased VAS for sensation scores. Quality of life,
      and disability changes were not observed. CONCLUSION: Our results indicate that a
      five day course of anodal tDCS is able to ameliorate tactile sensory loss with
      long-lasting beneficial effects and could thus represent a therapeutic tool for
      the treatment of tactile sensory deficit in MS patients.

PMID- 23122919
TI  - Quantitative PCR detection and improved sample preparation of microcystin
      producing Anabaena, Microcystis and Planktothrix.
AB  - Blooms of toxic cyanobacteria, associated with illness and mortality in humans
      and animals, are becoming increasingly common worldwide. The safe use of surface
      waters for drinking water production and recreation necessitates assessment of
      toxigenic cyanobacteria. We have developed simple and reliable sample preparation
      and qPCR methods to detect microcystin-producing strains of three major bloom
      forming genera, Anabaena, Microcystis and Planktothrix. The mcyB second
      thiolation motif, previously not recognized as a potential target for qPCR, was
      used as a basis for primer and genus-specific probe design. Assay specificity and
      sensitivity was confirmed with cultured cyanobacterial strains and the effect of
      different sample preparation methods on quantification was investigated. Sample
      filtration and cell lysis reduced assay time and resulted in more efficient
      amplification compared to DNA extraction. Positive correlation (p<0.005) between
      mcyB copy numbers and microcystin concentrations was observed in environmental
      samples. The results encourage the use of qPCR in water risk management.

PMID- 23122920
TI  - Age-related changes in neuroactive steroid levels in 3xTg-AD mice.
AB  - Although neuroactive steroids exert neuroprotective actions in different
      experimental models of neurodegenerative diseases, including those of Alzheimer's
      disease (AD), their relationships with aged related physiologic and pathologic
      brain changes remain to be clarified. In this study the levels of pregnenolone,
      dehydroepiandrosterone, progesterone, dihydroprogesterone,
      tetrahydroprogesterone, isopregnanolone, testosterone, dihydrotestosterone,
      5alpha-androstane-3alpha,17beta-diol, 5alpha-androstane-3beta,17beta-diol,
      17alpha-estradiol, and 17beta-estradiol were assessed in the limbic region of
      young adult (7 months) and aged (24 months) male wild type and triple transgenic
      AD mice. Age related neuropathological changes in AD brains, such as beta-amyloid
      accumulation and gliosis, were associated with modified levels of specific
      neuroactive steroids and particularly with changes in the levels of progesterone
      and testosterone metabolites. The altered levels of neuroactive steroids in aged
      AD brains might impact on the activation of neuroprotective signaling mediated by
      classic and nonclassic steroid receptors, like the gamma-aminobuttyric acid
      (GABA)-A receptor.

PMID- 23122921
TI  - Chemical-physical characterization of isolated plant cuticles subjected to low
      dose gamma-irradiation.
AB  - Isolated tomato fruit cuticles were subjected to low dose (80Gy) gamma
      irradiation, as a potential methodology to prevent harvested fruit and vegetables
      spoilage. Both irradiated and non-irradiated samples have been morphologically
      and chemically characterized by scanning electron (SEM), atomic force (AFM),
      attenuated total reflectance Fourier transform infrared (ATR-FTIR) and X-ray
      photoelectron (XPS) spectroscopies. Additionally, electrochemical measurements
      comprising membrane potential and diffusive permeability were carried out to
      detect modifications in transport properties of the cuticle as the fruit primary
      protective membrane. It has been found that low dose gamma-irradiation causes
      some textural changes on the surface but no significant chemical modification.
      Texture modification is found to be due to a partial removal of outermost
      (epicuticular) waxes which is accompanied by mild changes of electrochemical
      parameters such as the membrane fixed charge, cation transport number and salt
      permeability. The modification of such parameters indicates a slight reduction of
      the barrier properties of the cuticle upon low dose gamma-irradiation.

PMID- 23122922
TI  - Early corticospinal tract Wallerian degeneration on diffusion-weighted MR imaging
      after adult stroke: three cases report.

PMID- 23122923
TI  - Holistic health: predicting our data future (from inter-operability among systems
      to co-operability among people).
AB  - Data depend on processes; processes depend on organizational models;
      organizational models depend on regulations and policies. This position paper
      envisages the future data scenarios and the related research needs by addressing
      this whole logical chain. A 'smarter health and wellness future' requires the
      proactive engagement of citizens and of their caregivers, and the cooperation of
      health professionals across care facilities, with intense usage of mobile
      communication and connected devices. This ecosystem of people and organizations
      is currently extremely fragmented. Technology offers the possibility to mediate
      among the different actors in order to build a functional care team around the
      specific needs of each individual, i.e. a 'virtual facility'. However, this
      requires policies and regulations in every jurisdiction that motivate providers
      and their organizations to collaborate among themselves and with citizens
      according to explicit individual plans of care provision, to share their goals
      and negotiate their respective roles with respect to each citizen. Once a
      collaborative organizational context is established within integrated care
      models, policy makers could identify a critical mass of relevant shared processes
      and isolate a set of 'Attention Points' with predictable actors, concerns,
      activities, and thus highly precise information needs. For each Attention Point,
      a template for a Context-Specific Profile of the patient could be produced, e.g.
      as an HL7-CDA schema that fully specifies the mandatory and optional (clinical)
      data useful to support the care processes and to manage governance indicators. In
      relation to these predictable Attention Points data sources can be aligned to
      achieve reasonable coherence and consistency. Attention to data quality can be
      improved in a context of systematic re-use of the same data by different actors
      in different contexts. From a collection of profiles it could be possible to set
      up the core of a multi-purpose "Policy-Oriented" Health Record (POHR), shared by
      the functional care team in the citizen's ecosystem. In fact, the shared
      management of selected clinical data should be no more based on the a posteriori
      extraction from the personal notes of each professional, but on the cooperative
      construction of a systemic resource, together with the administrative and
      organizational data, able to support the management of innovative, integrated
      care models. In addition, the policy-oriented focus on routine data within a set
      of predictable situations makes it possible to stratify an appropriate number of
      citizens into homogeneous classes and to produce timely indicators of processes
      and outcomes from routine data for governance purposes, e.g. to optimize the
      allocation of resources, to drive continuous education, or to promote
      epidemiological studies.

PMID- 23122924
TI  - Parental evaluation of postoperative outcome of circumcision with Plastibell or
      conventional dissection by dorsal slit technique: a randomized controlled trial.
AB  - AIM: To evaluate and compare parental satisfaction after Plastibell and
      conventional dissection circumcision. METHODS: 198 children were randomly and
      equally allocated to two groups (PD: Plastibell and CDS: dissection) for
      circumcision. Follow-up was done at 7th, 15th and 90th day after surgery. Written
      questionnaires were given to parents at the time of discharge to complete and
      return at the 15th and 90th day follow-up visits. RESULTS: Both groups were
      balanced with respect to various demographic factors, indications for surgery and
      Kayaba's classification of the prepuce. Surgical duration was significantly
      shorter for the PD as compared to the CDS group (5.91 +/- 1.74 min vs. 23.52 +/-
      5.94 min; p < 0.0001 H.S.). Swelling, dysuria and infection were the prominent
      problems reported in both groups in the first 7 days. The Plastibell separated
      earlier in younger children (p < 0.0001). Postoperatively, children in the PD
      group required 2.79 fold more analgesic than those in the CDS group. 97.9% of
      parents in the PD group and 80.2% of parents in the CDS group claimed
      satisfactory aesthetic results. The PD group parents were statistically
      significantly more concerned about swelling. CONCLUSIONS: Plastibell use has
      comparable outcomes to the conventional dissection technique for paediatric
      circumcision and has an obvious advantage of shorter surgical duration. However,
      it is less comfortable in the postoperative period due to swelling, and requires
      greater use of analgesics.

PMID- 23122925
TI  - Minimal modifications could decrease fistula rate during tubularized incised
      plate procedure in distal hypospadias repair.
AB  - AIM: To report outcome of technical modifications to minimize fistula after TIP
      procedure. PATIENTS AND METHODS: 369 boys presenting with distal hypospadias were
      divided into two groups. In group 1, 196 underwent the standard TIP procedure. In
      the 173 patients in group 2, several modifications were incorporated into the TIP
      repair: 1) the first proximal suture was U-shaped subepithelial, 2) dartos flap
      was created on ventral aspect of penis to cover the proximal suture, and 3) the
      midline release incision was done as a first step. Patients were monitored
      prospectively for fistulae, chordee, meatal position, stenosis, and evaluated
      postoperatively at regular intervals. RESULTS: 362 patients had a good cosmetic
      appearance with slit-shaped meatus. Urethrocutaneous fistula was seen in 9 (4.6%)
      in group 1 and 4 (2.3%) in group 2. Urinary streams were of good quality and
      without fistula in 187 in group 1 and 169 in group 2. Glans dehiscence was seen
      in 7 (4 in group 1 and 3 in group 2), meatal stenosis and new urethral stricture
      in 15 (6 in group 1 and 9 in group 2). Glanular appearance was excellent except
      in those 7 patients who had glans dehiscence, and the phallus was straight in
      all. CONCLUSION: The Snodgrass repair has revolutionized the treatment of
      hypospadias. These technical modifications combined with careful patient
      selection achieved a low fistula rate.

PMID- 23122926
TI  - Monitoring uterine activity during labor: a comparison of 3 methods.
AB  - OBJECTIVE: Tocodynamometry (Toco; strain gauge technology) provides contraction
      frequency and approximate duration of labor contractions but suffers frequent
      signal dropout, necessitating repositioning by a nurse, and may fail in obese
      patients. The alternative invasive intrauterine pressure catheter (IUPC) is more
      reliable and adds contraction pressure information but requires ruptured
      membranes and introduces small risks of infection and abruption.
      Electrohysterography (EHG) reports the electrical activity of the uterus through
      electrodes placed on the maternal abdomen. This study compared all 3 methods of
      contraction detection simultaneously in laboring women. STUDY DESIGN: Upon
      consent, laboring women were monitored simultaneously with Toco, EHG, and IUPC.
      Contraction curves were generated in real-time for the EHG, and all 3 curves were
      stored electronically. A contraction detection algorithm was used to compare
      frequency and timing between methods. Seventy-three subjects were enrolled in the
      study; 14 were excluded due to hardware failure of 1 or more of the devices (n =
      12) or inadequate data collection duration (n = 2). RESULTS: In comparison with
      the gold-standard IUPC, EHG performed significantly better than Toco with regard
      to the Contractions Consistency Index (CCI). The mean CCI for EHG was 0.88 +/-
      0.17 compared with 0.69 +/- 0.27 for Toco (P < .0001). In contrast to Toco, EHG
      was not significantly affected by obesity. CONCLUSION: Toco does not correlate
      well with the gold-standard IUPC and fails more frequently in obese patients. EHG
      provides a reliable noninvasive alternative, regardless of body habitus.

PMID- 23122927
TI  - Vaginal progesterone or cerclage to prevent recurrent preterm birth?

PMID- 23122928
TI  - The use of cyclic nitroxide radicals as HNO scavengers.
AB  - Reduction of cyclic stable nitroxides (RNO) by HNO to the respective
      hydroxylamines (RNO-H) has been demonstrated using EPR spectrometry. HNO shows
      low reactivity toward piperidine, pyrrolidine and nitronyl nitroxides with rate
      constants below 1.4 * 10(5)M(-1)s(-1) at pH 7.0, despite the high driving force
      for these reactions. The rate constants can be predicted assuming that the
      reactions take place via a concerted proton-electron transfer pathway and
      significantly low self-exchange rate constants for HNO/NO and RNO-H/RNO. NO does
      not react with piperidine and pyrrolidine nitroxides, but does add to HNO forming
      the highly oxidizing and moderately reducing hyponitrite radicals. In this work,
      the radicals are produced by pulse radiolysis and the rate constants of their
      reactions with 2,2,6,6,-tetramethylpiperidine-1-oxyl (TEMPO), 4-hydroxy-2,2,6,6
      tetramethyl piperidine-1-oxyl (TEMPOL) and 3-carbamoyl-PROXYL have been
      determined at pH 6.8 to be (2.4 +/- 0.2)* 10(6), (9.8 +/- 0.2)* 10(5), (5.9 +/-
      0.5)* 10(5)M(-1)s(-1), respectively. This low reactivity implies that NO competes
      efficiently with these nitroxides for the hyponitrite radical. The ability of
      TEMPOL and 2-(4-carboxyphenyl)-4,4,5,5,-tetramethyl-imidazoline-1-oxyl-3-oxide (C
      PTIO) to oxidize HNO and their different reactivity toward NO are used to
      quantify HNO formed via acetohydroxamic acid oxidation. The extent of TEMPOL or C
      PTIO reduction was similar to the yield of HNO formed upon oxidation by ()OH
      under anoxia, but not by the metmyoglobin and H(2)O(2) reaction system where both
      nitroxides catalytically facilitate H(2)O(2) depletion and nitrite accumulation.
      In this system the conversion of C-PTIO into 2-(4-carboxyphenyl)-4,4,5,5
      tetramethylimidazoline-1-oxyl (C-PTI) is a minor reaction, which does not provide
      any mechanistic insight.

PMID- 23122929
TI  - Tumor-associated macrophages, epidermal growth factor receptor correlated with
      the triple negative phenotype in endometrial endometrioid adenocarcinoma.
AB  - It has been well established that tumor-associated macrophages (TAMs) play a
      tumor-promoting role in endometrial endometrioid adenocarcinoma (EEC). However,
      the association with TAMs and the triple-negative phenotype (TNP) in EEC has not
      yet been reported. We used immunohistochemistry to examine the expression of
      CD68, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth
      factor receptor 2 (HER2), and epidermal growth factor receptor (EGFR) in 186
      cases of EEC. Fluorescent in situ hybridization (FISH) was also used for HER2
      amplification, and the association with TAMs count, EGFR expression, and triple
      negative phenotype was analyzed. Twenty-eight of 186 patients (15.05%) had the
      TNP. It was associated with advanced stage disease (P<0.0001), high grade disease
      (P<0.0001), depth of myometrial invasion (P=0.003), pelvic lymph node metastasis
      (P<0.001), lymphovascular space invasion (P=0.001), and EGFR expression
      (P=0.032). Margin TAMs count was also significantly increased in the TNP-positive
      group, the EGFR-positive group, and the PR-negative group (P<0.001,
      respectively). The TNP was associated with a significantly worse overall survival
      (OS) (log rank test, P=0.018). The estimated 5-year OS of patients with TNP was
      59.1%, while that without TNP was 78.5%. Multivariate analysis showed high margin
      TAMs, and the histopathological grades were significantly associated with OS. The
      TNP in EEC is associated with poor prognostic surgical-pathological factors,
      worse prognosis, as well as with high margin TAMs and overexpression of EGFR,
      which may serve as potential targeted therapies for the special phenotype in EEC.

PMID- 23122930
TI  - Long-term results of liver resection for hepatocellular carcinoma in noncirrhotic
      liver.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is among the most common malignant
      neoplasms worldwide. Only few data on HCC in noncirrhotic livers without viral
      hepatitis in Western countries are available. The purpose of this study was to
      define the outcomes and potential prognostic factors associated with survival
      after hepatic resection in patients with HCC in the absence of liver cirrhosis
      and hepatitis B or C infection. PATIENTS AND METHODS: From January 2000 to
      September 2010, 148 patients without liver cirrhosis and without extrahepatic
      metastases underwent curative hepatic resection for HCC at the Surgical
      Department of the Charite, Campus Virchow Klinikum. The outcomes of these
      patients were retrospectively reviewed. Patients with cirrhosis or severe
      fibrosis, fibrolamellar HCC, and those positive for hepatitis B or C were
      excluded. RESULTS: The cumulative 1-, 3-, 5-, and 7-year survival rates were
      75.4%, 54.7%, 38.9%, and 31.8%, respectively. The 1-, 3-, 5-, and 7-year disease
      free survival rates were 60.3%, 38.0%, 29.1%, and 18.1%, respectively. In the
      multivariate analysis, cumulative survival was decreased by patient age,
      increased operative time, increased preoperative serum gamma-glutamyl transferase
      (GGT), and tumor stage. In the subgroup with unifocal neoplasms, N0 and R0
      status, tumor size >10 cm, and tumor differentiation were highly predictive of
      lesser survival. Unfavorable survival was observed in patients with multifocal
      neoplasms, tumor size >10 cm, and/or poor tumor differentiation. CONCLUSION: The
      current TNM staging system is stratified for survival and recurrence. Extension
      of the current TNM staging system by grading and more exact differentiation of
      tumor size may increase its prognostic accuracy for predicting outcome.
      Preoperative increased serum GGT level could be a new poor prognostic factor.

PMID- 23122931
TI  - Confronting the chronically anticoagulated, acute care surgery patient as we
      evolve into the post-warfarin era.
AB  - There are a growing number of new anticoagulants used as an alternative to
      warfarin. Surgeons will be confronted with an increasing number of patients who
      may be on these outpatient medications and must be familiar with their management
      strategies. The purpose of this review is to examine the mechanisms, monitoring
      and therapeutic reversal of the non-warfarin antithrombotic agents now so
      frequently confronting the acute care surgeon.

PMID- 23122932
TI  - The use of vacuum-assisted wound closure therapy in thoracic operations.
AB  - BACKGROUND: Conventional treatment of complex, nonresolving empyemas after an
      episode of pneumonia or a chest operation often requires an open-window
      thoracostomy. This necessitates frequent, often painful dressing changes and is
      associated with prolonged hospitalization. The wound is often malodorous, causing
      significant social distress to patients and unquestionably affects their quality
      of life. We assessed the value of using vacuum-assisted closure (VAC) therapy in
      managing patients with a persistent infected pleural space. METHODS: The study
      included 10 patients. All patients signed an informed consent and were debriefed
      before the procedure. An empyema developed in 1 patient after an episode of
      pneumonia. The other 9 had recently undergone a thoracic surgical procedure. All
      patients underwent initial open drainage of the pleural cavity and debridement. A
      VAC therapy system was then inserted intraoperatively or on the first
      postoperative day. The patients were discharged home with a portable VAC therapy
      system in situ. Subsequent dressing changes were managed by tissue-viability
      nurses in the community, without the need for further anesthesia or analgesia.
      Over a period of time, the cavity was sterilized and eventually obliterated
      spontaneously. RESULTS: All patients were mobilized early and fast-tracked
      through the hospital. This prevented the need for daily dressing changes; hence,
      minimizing the disruption of normal activities and reducing the need for nursing
      care. Overall, the length of hospitalization was shorter, and the VAC therapy
      facilitated closure of the infected wound cavity. The use of the VAC therapy
      system negated the need for a second surgical procedure to close the wound
      cavity. None of the patients reported pain, odor, or inconvenience associated
      with the VAC therapy system. CONCLUSIONS: Our observations suggest that the use
      of VAC therapy to treat such patients is safe, facilitates early discharge and
      recovery, and offers a "civilized," cost-effective treatment in a community
      setting.

PMID- 23122933
TI  - Synthesis and biological evaluation of new fluorine substituted derivatives as
      angiotensin II receptor antagonists with anti-hypertension and anti-tumor
      effects.
AB  - The synthesis and pharmaceutical activity of new potent non-tetrazole angiotensin
      II (Ang II) receptor antagonists were described. These compounds were fluorine
      substituted derivatives of Losartan, Valsartan and Irbesartan with carboxylic
      acid group as replacements to the known potent tetrazole moiety at the 2'
      biphenyl position. Their activities were evaluated by Ang II receptor binding
      assay as well as by in vivo assay. All of the synthesized compounds showed
      nanomolar affinity for the AT(1) receptor subtype. The vivo biological evaluation
      showed that compounds 1a, 2 and 4 produced a dose-dependent antihypertensive
      effect both in spontaneously hypertensive rats (SHR) and renal hypertensive rats
      (RHR). Compound 4 especially showed an efficient and long-lasting effect in
      reducing blood pressure which can last more than 24 h at dose of 10 mg/kg in SHR,
      which was much better than control Losartan and Valsartan. Compound 4 can also
      inhibit the prostate cancer in vitro and in vivo. So compound 4 was selected for
      in-depth investigation as potent, novel and long-lasting non-tetrazole anti
      hypertension and anti-tumor drug candidate.

PMID- 23122934
TI  - Inhibition of monoamine oxidase by 8-[(phenylethyl)sulfanyl]caffeine analogues.
AB  - In a previous study we have investigated the monoamine oxidase (MAO) inhibitory
      properties of a series of 8-sulfanylcaffeine analogues. Among the compounds
      studied, 8-[(phenylethyl)sulfanyl]caffeine (IC(50) = 0.223 MUM) was found to be a
      particularly potent inhibitor of the type B MAO isoform. In an attempt to
      discover potent MAO inhibitors and to further examine the structure-activity
      relationships (SAR) of MAO inhibition by 8-sulfanylcaffeine analogues, in the
      present study a series of 8-[(phenylethyl)sulfanyl]caffeine analogues were
      synthesized and evaluated as inhibitors of human MAO-A and -B. The results
      document that substitution on C3 and C4 of the phenyl ring with alkyl groups and
      halogens yields 8-[(phenylethyl)sulfanyl]caffeine analogues which are potent and
      selective MAO-B inhibitors with IC(50) values ranging from 0.017 to 0.125 MUM.
      The MAO inhibitory properties of a series of 8-sulfinylcaffeine analogues were
      also examined. The results show that, compared to the corresponding 8
      sulfanylcaffeine analogues, the 8-sulfinylcaffeins are weaker MAO-B inhibitors.
      Both the 8-sulfanylcaffeine and 8-sulfinylcaffeine analogues were found to be
      weak MAO-A inhibitors. This study also reports the MAO inhibition properties of
      selected 8-[(phenylpropyl)sulfanyl]caffeine analogues.

PMID- 23122935
TI  - Synthesis of 6"-triazole-substituted alpha-GalCer analogues as potent iNKT cell
      stimulating ligands.
AB  - We report the synthesis of a small series of 6"-triazol-1-yl-substituted alpha
      GalCer analogues by late-stage conversion of the 6"-OH to an azide group, copper
      catalyzed azide-alkyne cycloaddition and final deprotection. When evaluated for
      their capacity to induce IL-2 secretion in vitro, all compounds proved equally
      potent or superior to alpha-GalCer. The S.A.R suggests that the improved
      antigenic activity is mainly triggered by the triazole functionalization in se.
      While the introduction of selected substitutuents at C-4 of this heterocyclic
      ring is tolerated, this generally fails to further improve antigenicity.

PMID- 23122936
TI  - DNA binding acridine-thiazolidinone agents affecting intracellular glutathione.
AB  - Three new acridine-thiazolidinone derivatives (2a-2c) have been synthesized and
      their interactions with calf thymus DNA and a number of cell lines (leukemic
      cells HL-60 and L1210 and human epithelial ovarian cancer cell lines A2780) were
      studied. The compounds 2a-2c possessed high affinity to calf thymus DNA and their
      binding constants determined by spectrofluorimetry were in the range of 1.37 *
      10(6)-5.89 * 10(6) M(-1). All of the tested derivatives displayed strong
      cytotoxic activity in vitro, the highest activity in cytotoxic tests was found
      for 2c with IC(50) = 1.3 +/- 0.2 MUM (HL-60), 3.1 +/- 0.4 MUM (L1210), and 7.7 +/
      0.5 MUM (A2780) after 72 h incubation. The cancer cells accumulated acridine
      derivatives very fast and the changes of the glutathione level were confirmed.
      The compounds inhibited proliferation of the cells and induced an arrest of the
      cell cycle and cell death. Their influence upon cells was associated with their
      reactivity towards thiols and DNA binding activity.

PMID- 23122937
TI  - Triazole pyrimidine nucleosides as inhibitors of Ribonuclease A. Synthesis,
      biochemical, and structural evaluation.
AB  - Five ribofuranosyl pyrimidine nucleosides and their corresponding 1,2,3-triazole
      derivatives have been synthesized and characterized. Their inhibitory action to
      Ribonuclease A has been studied by biochemical analysis and X-ray
      crystallography. These compounds are potent competitive inhibitors of RNase A
      with low MUM inhibition constant (K(i)) values with the ones having a triazolo
      linker being more potent than the ones without. The most potent of these is 1
      [(beta-D-ribofuranosyl)-1,2,3-triazol-4-yl]uracil being with K(i) = 1.6 MUM. The
      high resolution X-ray crystal structures of the RNase A in complex with three
      most potent inhibitors of these inhibitors have shown that they bind at the
      enzyme catalytic cleft with the pyrimidine nucleobase at the B(1) subsite while
      the triazole moiety binds at the main subsite P(1), where P-O5' bond cleavage
      occurs, and the ribose at the interface between subsites P(1) and P(0) exploiting
      interactions with residues from both subsites. The effect of a susbsituent group
      at the 5-pyrimidine position at the inhibitory potency has been also examined and
      results show that any addition at this position leads to a less efficient
      inhibitor. Comparative structural analysis of these RNase A complexes with other
      similar RNase A-ligand complexes reveals that the triazole moiety interactions
      with the protein form the structural basis of their increased potency. The
      insertion of a triazole linker between the pyrimidine base and the ribose forms
      the starting point for further improvement of these inhibitors in the quest for
      potent ribonucleolytic inhibitors with pharmaceutical potential.

PMID- 23122938
TI  - Backward walking measures are sensitive to age-related changes in mobility and
      balance.
AB  - Many falls occur from backward perturbations or during transitional movements
      that require a person to turn and step backwards, suggesting that deficits in
      backward stepping may negatively impact mobility. Previous studies found
      significant declines in backward walking (BW) spatiotemporal measures in healthy
      elderly compared to young adults. No studies to date have examined BW performance
      in middle-aged adults and in elderly with impaired mobility. This study compared
      spatiotemporal measures of BW and forward walking (FW) in young, middle-aged, and
      elderly and in elderly fallers and non-fallers; and compared the strength of the
      relationship between age and BW and FW spatiotemporal measures to determine the
      utility of BW performance as a clinical tool for examining safety and mobility.
      BW measures were significantly more impaired in the elderly (n=62) compared to
      young (n=37) and middle-aged (n=31) adults and age effects were greater in BW
      than FW. No significant differences were found between young and middle-aged
      except for base of support in BW. Stronger correlations were found between age
      and BW measures than between age and FW measures, particularly correlations
      between age and BW velocity and stride length. Elderly fallers had greater
      deficits in BW performance than non-fallers. All elderly fallers had BW
      velocities<.6m/s. Clinicians are encouraged to assess BW, particularly BW
      velocity, as part of mobility examinations.

PMID- 23122939
TI  - [Oral health of users of psychoactive substances].
AB  - The oral health of drug users is increasingly part of the medical universe of
      caregivers. For too long, the place of oral health in the "good living" was very
      thin. The mouth of a patient interests very few people, and still less the person
      himself who begins to worry that very late. His entourage has a lot of other
      reasons for concern and the dentist is infrequently associated to support teams
      in a global approach to public health, and a fortiori as caregiver.

PMID- 23122940
TI  - [Criteria of the patient's decision concerning vaccination against influenza
      AH1N1, in Belgium and France].
AB  - INTRODUCTION: We have analyzed the reasons evoked by the patients to decide or
      not to be vaccinated against AH1N1 influenza, in France and Belgium. METHODS:
      Semi-structured interviews were performed, recorded and transcribed for analysis.
      Fifty-eight interviews were performed with patient living in the region of Midi
      Pyrenees, France (21 interviews) and in the province of Liege, Belgium (37
      interviews). The patients were recruited by general practitioners. Within the
      sample, some patients were vaccinated against AH1N1 influenza and others were
      not. RESULTS: Five criteria influenced the decision to be vaccinated or not: how
      people understand the epidemic and the threats it represents; their
      representation about the vaccine (and its harmlessness); their beliefs and
      representations about vaccination; the influence of the health professionals'
      opinion; the discussions between the patient and his acquaintances; and how the
      patient seeks for information. CONCLUSION: These elements can be considered as
      criteria influencing the decision about any vaccination. They reflect the
      patient's subjectivity, the patient's perception of vaccination. Investigating
      these dimensions in the patient's mind can help the practitioner to positively
      influence the reluctant patients. Identifying threats and received ideas should
      allow the doctor to correct them and accept vaccination.

PMID- 23122941
TI  - [Which indications and access routes for transcatheter aortic valve implantation?
      Health technology assessment from HAS].
AB  - The transcatheter aortic valve implantation should be restricted to patients with
      severe symptomatic aortic stenosis with a contraindication for a surgical
      replacement (taking into account surgical risk scores, comorbidities, anatomical
      conditions, life expectancy and frailty). Patient eligibility should be performed
      by a heart team with the involvement of a cardiac surgeon, an interventional
      cardiologist, a clinical cardiologist and an anaesthetist/resuscitation
      specialist. The advice of a geriatrician is strongly recommended. The long-term
      efficacy remains unknown. The French National Authority for Health (Haute
      Autorite de sante [HAS]) reminds that contraindications in the CE mark should be
      strictly respected (i.e.instructions for use). Extension of current indications
      should be conditional to the presentation of clinical evidence. Thus,
      implantation in patients at lower surgical risk or the use of direct transaortic
      route are not eligible for reimbursement given the current state of knowledge.

PMID- 23122942
TI  - [Opiates, harm reduction and polysubstance abuse].
AB  - Opioid dependence is a chronic metabolic brain disease and several individual,
      sociological and biological factors are implicated in its development. Program
      (needle exchange, low threshold access to treatment) prevent harms associated
      with opioid use (HIV, overdose...). Effective treatment involves a set of
      pharmacological and psychosocial interventions. The benefits of maintenance
      programmes increase as long as the person remains in treatment (many years).
      Relapse is a symptom of the disorder or a sign of abstinence failure. Treatment
      aims to improve quality of life in a comprehensive and individualised assessment.

PMID- 23122943
TI  - [Addictions: A new approach].

PMID- 23122944
TI  - [Environment and addictive behaviors].
AB  - Consumer society creates the emergence of addictive behaviors and environments of
      the subject "shape" the use of psychoactive substances. The family approach is to
      search out a guilt of members to understand family dynamics and enable young
      people to emancipate themselves from the family model. The social environment
      contributes to the marginalization of drug users "pathologizing" his conduct.
      Offer help without preconditions and a relationship based on a therapeutic
      alliance can contribute decisively to the recovery of an addict. The prison is a
      place of initiation of use and consumption of psychoactive substances despite the
      offer of specialized treatment. Measures of risk reduction of HCV/HIV infection
      and alternatives to incarceration should complete it. At workplace, consumption
      can be considered as a mean of doping to be more "efficient", but also as an
      attempt to withstand the stresses and changes in working conditions in the
      context of individualization and a loss of marks related to the new way of
      organizing work.

PMID- 23122945
TI  - Serial analysis of lumen geometry and hemodynamics in human arteriovenous fistula
      for hemodialysis using magnetic resonance imaging and computational fluid
      dynamics.
AB  - The arteriovenous fistula (AVF) is the preferred form of vascular access for
      maintenance hemodialysis, but it often fails to mature to become clinically
      usable, likely due to aberrant hemodynamic forces. A robust pipeline for serial
      assessment of hemodynamic parameters and subsequent lumen cross-sectional area
      changes has been developed and applied to a data set from contrast-free MRI of a
      dialysis patient's AVF collected over a period of months after AVF creation
      surgery. Black-blood MRI yielded images of AVF lumen geometry, while cine phase
      contrast MRI provided volumetric flow rates at the in-flow and out-flow
      locations. Lumen geometry and flow rates were used as inputs for computational
      fluid dynamics (CFD) modeling to provide serial wall shear stress (WSS), WSS
      gradient, and oscillatory shear index (OSI) profiles. The serial AVF lumen
      geometries were co-registered at 1mm intervals using respective lumen
      centerlines, with the anastomosis as an anatomical landmark. Lumen enlargement
      was limited at the vein region near the anastomosis and a downstream vein valve,
      potentially attributed to the physical inhibition of wall expansion at those
      sites. This work is the first serial and detail study of lumen and hemodynamic
      changes in human AVF using MRI and CFD. This novel protocol will be used for a
      multicenter prospective study to identify critical hemodynamic factors that
      contribute to AVF maturation failure.

PMID- 23122946
TI  - Advanced age affects the individual leg mechanics of level, uphill, and downhill
      walking.
AB  - Advanced age brings biomechanical changes that may limit the uphill and/or
      downhill walking ability of old adults. Here, we investigated how advanced age
      alters individual leg mechanics during level, uphill, and downhill walking. We
      hypothesized that, compared to young adults, old adults would exhibit: (1)
      reduced trailing leg propulsive ground reaction forces (GRFs) and positive work
      rates during uphill walking, and (2) reduced leading leg braking ground reaction
      forces and negative work rates during downhill walking. We calculated the
      individual leg mechanical work performed by 10 old (mean+/-SD, age: 72+/-5 yrs)
      and 11 young (age: 26+/-5 yrs) adults walking at 1.25 m/s on a dual-belt force
      measuring treadmill at seven grades (0 degrees  and +/-3 degrees , +/-6 degrees ,
      +/-9 degrees ). As hypothesized, old adults exhibited significantly reduced
      propulsive GRFs (e.g., -21% at +9 degrees ) and average trailing leg positive
      work rates (e.g., -26% at +9 degrees ) compared to young adults during both level
      and uphill walking. Old adults compensated by performing greater positive work
      than young adults during the subsequent single support phase. In contrast, we
      reject our second hypothesis. We found no differences in braking GRFs or negative
      work rates between old and young adults. However, old adults exhibited
      significantly reduced second peak perpendicular GRFs during downhill walking
      compared to young adults. Our findings most notably identify how advanced age may
      impair uphill walking ability and thus independence and quality of life.

PMID- 23122947
TI  - Frequency of urinary incontinence in people with chronic heart failure.
AB  - OBJECTIVES: The purpose of the study was to examine the frequency and severity of
      urinary incontinence in people with heart failure (HF). Secondary aims were to
      determine the differences in known risk factors for those who were continent and
      incontinent, to investigate the correlates of urinary incontinence in people with
      HF, and to examine the relationship between urinary incontinence with medication
      adherence, in particular, diuretics, and quality of life. BACKGROUND: Urinary
      incontinence is a common condition affecting older adults. However, the frequency
      of incontinence in people with HF remains largely unknown. METHODS: This was a
      descriptive study. A convenience sample of 181 people with HF were surveyed to
      determine frequency, severity and presence of risk factors of urinary
      incontinence and dosages of prescribed HF medications. Instruments included the
      Revised Urinary Incontinence Scale, Medication Adherence Report Scale and
      Incontinence Impact Questionnaire Short Form. Regression analyses were used to
      examine relationships between variables and presence of urinary incontinence.
      RESULTS: Eighty-nine people responded (66% male, mean age 67 years), 44 (49%)
      self-reporting urinary incontinence. Of these, 30 (34%) respondents rated their
      incontinence severity as slight or moderate. More incontinent respondents took
      furosemide doses greater than 20 mg daily (P = 0.046) and low doses of beta
      blockers compared with continent respondents (P = 0.002). Taking low doses of
      beta-blockers explained 23% of variance for urinary incontinence (r(2) = 0.23, P
      = 0.015). Incontinent respondents reported altering or missing a diuretic dose (P
      < 0.02) compared with those who were continent. CONCLUSIONS: Frequency of urinary
      incontinence in this group of people with HF appears high. It appears that
      screening for urinary incontinence may be important as part of routine care in HF
      management programmes. In addition, awareness of dosages of furosemide and beta
      blockers and in particular, adherence to diuretics also should be monitored.
      Prospective studies investigating these issues and the effect of targeted
      interventions are required.

PMID- 23122949
TI  - Leukemia inhibitory factor increases the invasiveness of trophoblastic cells
      through integrated increase in the expression of adhesion molecules and
      pappalysin 1 with a concomitant decrease in the expression of tissue inhibitor of
      matrix metalloproteinases.
AB  - OBJECTIVE: To identify the invasion-associated molecules during leukemia
      inhibitory factor-(LIF-)mediated increase in the invasion of trophoblast cells.
      DESIGN: Experimental study. SETTING: Research institution. PATIENT(S): None.
      INTERVENTION(S): Cultured trophoblastic HTR-8/SVneo cells were treated with LIF.
      MAIN OUTCOME MEASURE(S): Matrigel matrix-based invasion assay of HTR-8/SVneo
      cells. Signaling molecules associated with LIF-mediated increase in invasion were
      investigated by Western blot, cDNA microarray, quantitative reverse transcriptase
      polymerase chain reaction, immunofluorescence, immunohistochemistry, and gene
      silencing by siRNA. RESULT(S): Treatment of HTR-8/SVneo cells with LIF (50 ng/mL)
      led to a significant increase in invasion. Treatment with LIF also led to an
      increase in nuclear localization of activated STAT1 and STAT3. Among 237
      differentially expressed genes after LIF treatment, expression of pappalysin 1,
      SERPINB3, podoplanin, integrin beta3, ID1, ICAM1, and so on went up, while tissue
      inhibitor of matrix metalloproteinase 1 (TIMP1), TIMP2, and TIMP3 went down
      significantly. The presence of several of these proteins has also been
      demonstrated in human trophoblast cells. Silencing of pappalysin 1 led to a
      significant reduction in basal as well as LIF-mediated invasiveness of HTR
      8/SVneo cells. CONCLUSION(S): Identification of novel molecules associated with a
      LIF-mediated increase in trophoblastic cell invasion may facilitate our
      understanding of implantation biology.

PMID- 23122948
TI  - Renal consequences of intraabdominal hypertension in a porcine model. Search for
      the choice indirect technique for intraabdominal pressure measurement.
AB  - OBJECTIVE: To study the effects on the renal system in a porcine model of
      intraabdominal hypertension, and to determine the indirect technique of choice
      for determination of the intraabdominal pressure. MATERIAL AND METHODS: 30 pigs
      were used divided in two groups according with increased intraabdominal pressure
      values (20 mmHg and 30 mmHg). In both groups pressures were registered 8 times,
      summing up to 3 hours, with a CO2 insufflator. Three different measures of the
      intraabdominal pressure were taken: a direct transperitoneal measure, using a
      catheter of Jackson-Pratt connected to a pressure transducer, and two indirect
      measures, a transvesical by means of a Foley to manometer system, and a
      transgastric by introducing in the stomach a catheter connected to a pressure
      monitor with electronic hardware. Mean arterial pressure was calculated, along
      with the cardiac index, production of urine and serum creatinine. RESULTS: There
      was a greater correlation between the transvesical and the transperitoneal
      intraabdominal pressures (R(2)=0,95). Average transgastric intraabdominal
      pressure was inferior to the transperitoneal indicator in all taken measurements.
      The average arterial pressure descended in both groups, with earlier significant
      differences observed at 30 mmHg (p<0,020). Urine production was lower at 30 mmHg
      compared with the 20 mmHg group (9,63 +/- 1,57 versus 3.26 ml +/- 1,73). Serum
      creatinine increased in both groups being pathological at 30 mmHg after 1h 20
      min, with existing differences between early pressures (p<0,027). CONCLUSIONS:
      This study revealed marked renal affectation with higher severity at 30 mmHg
      pressures. The transvesical technique showed a greater correlation with the
      direct measurement technique used, defining this as the method of choice for
      determination of intraabdominal pressure.

PMID- 23122950
TI  - Prenatal hyperandrogenism and lipid profile during different age stages: an
      experimental study.
AB  - OBJECTIVE: The present study investigates the effect of prenatal
      hyperandrogenization on lipid metabolism and oxidant/antioxidant balance. DESIGN:
      Experimental study. SETTING: Research institute. ANIMAL(S): Pregnant Sprague
      Dawley rats were subcutaneously injected with 2 mg free T between days 16 and 19
      of pregnancy, and controls (C) received vehicle (0.1 mL of sesame oil).
      Prenatally hyperandrogenized female offspring (T2) had a condition that resembles
      polycystic ovary (PCO). Animals were weighed and killed at 21 and 60 days of age
      (N = 15 rats/group). INTERVENTION(S): Ovarian tissue and truncal blood were
      obtained from the C and T2 groups. MAIN OUTCOME MEASURE(S): Circulating lipid
      profile (total cholesterol, high-density lipoprotein [HDL], low-density
      lipoprotein [LDL] cholesterol, and triglycerides) was quantified by colorimetric
      enzymatic methods. Ovarian oxidative stress was evaluated by quantifying lipid
      peroxidation and glutathione content by spectofotometric assays. Ovarian fat
      content was evaluated by Red Oil staining and ovarian messenger RNA (mRNA)
      expression of peroxisome proliferator-activated receptor gamma (PPAR-gamma) by
      real-time polymerase chain reaction (PCR). RESULT(S): At 60 days of age, 100% of
      group C rats and 20% of group T2 rats ovulated. At 21 days of age the T2 rats
      displayed lower body weight than C rats; however, at 60 days of age T2 and C rats
      showed similar body weights. The lipid profile (total cholesterol, LDL
      cholesterol, HDL cholesterol, and triglycerides) was altered in the anovulatory
      and ovulatory phenotype of the T2 group, but the levels were higher in the
      anovulatory phenotype. Lipid peroxidation of rats at 21 and 60 days of age from
      T2 was similar to C but the antioxidant glutathione level was decreased in 21-day
      old rats compared with C rats. The lipid content of ovarian tissue, determined by
      Red Oil staining, was higher in the T2 than in the C group. The mRNA expression
      of ovarian PPAR-gamma, quantified by real time PCR, decreased in anovulatory rats
      at 60 days of age from T2 compared to C rats. CONCLUSION(S): Our findings reveal
      the importance of evaluating the complete lipid profile, especially at early
      stages of life after the prenatal hyperandrogenism condition. In addition, we
      demonstrated that the antioxidant-reduced glutathione would represent a good
      marker of oxidative stress as it is altered before lipid peroxidation. Prenatal
      hyperandrogenization also alters the gene expression of PPAR-gamma in rats. Here
      we demonstrated for the first time that abnormalities in PPAR-gamma and lipid
      profile were higher in rats showing an anovulatory phenotype than those
      displaying an ovulatory phenotype.

PMID- 23122951
TI  - A microfluidic device to reduce treatment time of intracytoplasmic sperm
      injection.
AB  - OBJECTIVE: To develop a microfluidic device that can reduce the intracytoplasmic
      sperm injection (ICSI) treatment time by increasing sperm concentration. DESIGN:
      We compared the ICSI treatment time required for porcine sperm using a method
      employing the microfluidic device and one using the conventional microdroplet
      method. SETTINGS: Academic research laboratories at Okayama University.
      ANIMAL(S): Reproductive cells of porcine sperm, oocytes, and embryos.
      INTERVENTION(S): Cell manipulations, ICSI, and embryo culture. MAIN OUTCOME
      MEASURE(S): Average ICSI treatment time and sperm concentration. RESULT(S): The
      average ICSI treatment time (mean +/- SEM) using the method with the microfluidic
      device for poor-quality semen (sperm concentration, 2.0 * 10(4) cells/mL) was
      significantly shorter than the treatment time using the conventional microdroplet
      method (265 +/- 15 seconds [n = 43] vs. 347 +/- 19 seconds [n = 50]). When
      diluted semen with a sperm concentration of 2.0 * 10(5) cells/mL was used, no
      significant difference was observed between the two methods (n = 50 and n = 48).
      CONCLUSION(S): The microfluidic device can reduce the time required for ICSI
      treatment that is used to increase sperm concentration in poor-quality semen
      samples. The results suggest that this device may be clinically useful for ICSI
      treatment in human assisted reproductive technology.

PMID- 23122952
TI  - Cell-derived microparticles and vascular pregnancy complications: a systematic
      and comprehensive review.
AB  - OBJECTIVE: To assess current studies on the relationship between cell-derived
      microparticles (cMP) and recurrent miscarriages (RM) and pre-eclampsia (PE), and
      review the relationships between cMP and inflammatory and clot pathways,
      antiphospholipid antibodies (aPL), cytokines, and pregnancy complications.
      DESIGN: Systematic and comprehensive review of the literature from January 2000
      to January 2012. SETTING: Vall d'Hebron University Hospital. PATIENT(S): Women
      with recurrent miscarriages or PE, healthy nonpregnant women, and healthy
      pregnant women. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Comparison of cMP
      numbers and types among groups. RESULT(S): Platelet and endothelial cMP are
      increased in women with normal pregnancies compared with nonpregnant healthy
      women. Only five case-control studies regarding cMP and RM and 16 on cMP and PE
      were found to match our objective. Three of five articles referring to RM showed
      differences in cMP numbering, and 13 of 16 on cMP and PE showed differences in
      some type of cMP compared with controls. CONCLUSION(S): Cell-derived
      microparticles were raised in normal pregnancy. Recurrent miscarriage seems to be
      related to endothelial and platelet cell activation and/or consumption. An
      increase in almost all cMP types was observed in PE. A relationship between cMP
      and endothelial activation and proinflammatory status seems to exist.

PMID- 23122953
TI  - Uterus transplantation.

PMID- 23122954
TI  - The prevalence of traumatic brain injuries after minor blunt head trauma in
      children with ventricular shunts.
AB  - STUDY OBJECTIVE: We compare the prevalence of clinically important traumatic
      brain injuries and the use of cranial computed tomography (CT) in children with
      minor blunt head trauma with and without ventricular shunts. METHODS: We
      performed a secondary analysis of a prospective observational cohort study of
      children with blunt head trauma presenting to a participating Pediatric Emergency
      Care Applied Research Network emergency department. For children with Glasgow
      Coma Scale (GCS) scores greater than or equal to 14, we compared the rates of
      clinically important traumatic brain injuries (defined as a traumatic brain
      injury resulting in death, neurosurgical intervention, intubation for more than
      24 hours, or hospital admission for at least 2 nights for management of traumatic
      brain injury in association with positive CT scan) and use of cranial CT for
      children with and without ventricular shunts. RESULTS: Of the 39,732 children
      with blunt head trauma and GCS scores greater than or equal to 14, we identified
      98 (0.2%) children with ventricular shunts. Children with ventricular shunts had
      more frequent CT use: (45/98 [46%] with shunts versus 13,858/39,634 [35%]
      without; difference 11%; 95% confidence interval 1% to 21%) but a similar rate of
      clinically important traumatic brain injuries (1/98 [1%] with shunts versus
      346/39,619 [0.9%] without; difference 0.1%; 95% confidence interval -0.3% to 5%).
      The one child with a ventricular shunt who had a clinically important traumatic
      brain injury had a known chronic subdural hematoma that was larger after the head
      trauma compared with previous CT; the child underwent hematoma evacuation.
      CONCLUSION: Children with ventricular shunts had higher CT use with similar rates
      of clinically important traumatic brain injuries after minor blunt head trauma
      compared with children without ventricular shunts.

PMID- 23122955
TI  - A call to action for antimicrobial stewardship in the emergency department:
      approaches and strategies.

PMID- 23122956
TI  - DRAK2 participates in a negative feedback loop to control TGF-beta/Smads
      signaling by binding to type I TGF-beta receptor.
AB  - TGF-beta1 is a multifunctional cytokine that mediates diverse biological
      processes. However, the mechanisms by which the intracellular signals of TGF
      beta1 are terminated are not well understood. Here, we demonstrate that DRAK2
      serves as a TGF-beta1-inducible antagonist of TGF-beta signaling. TGF-beta1
      stimulation rapidly induces DRAK2 expression and enhances endogenous interaction
      of the type I TGF-beta receptor with DRAK2, thereby blocking R-Smads recruitment.
      Depletion of DRAK2 expression markedly augmented the intensity and the extent of
      TGF-beta1 responses. Furthermore, a high level of DRAK2 expression was observed
      in basal-like and HER2-enriched breast tumors and cell lines, and depletion of
      DRAK2 expression suppressed the tumorigenic ability of breast cancer cells. Thus,
      these studies define a function for DRAK2 as an intrinsic intracellular
      antagonist participating in the negative feedback loop to control TGF-beta1
      responses, and aberrant expression of DRAK2 increases tumorigenic potential, in
      part, through the inhibition of TGF-beta1 tumor suppressor activity.

PMID- 23122957
TI  - Proliferative and survival effects of PUMA promote angiogenesis.
AB  - The p53 upregulated modulator of apoptosis (PUMA) is known as an essential
      apoptosis inducer. Here, we report the seemingly paradoxical finding that PUMA is
      a proangiogenic factor critically required for the proliferation and survival of
      vascular and microglia cells. Strikingly, Puma deficiency by genetic deletion or
      small hairpin RNA knockdown inhibited developmental and pathological angiogenesis
      and reduced microglia numbers in vivo, whereas Puma gene delivery increased
      angiogenesis and cell survival. Mechanistically, we revealed that PUMA plays a
      critical role in regulating autophagy by modulating Erk activation and
      intracellular calcium level. Our findings revealed an unexpected function of PUMA
      in promoting angiogenesis and warrant more careful investigations into the
      therapeutic potential of PUMA in treating cancer and degenerative diseases.

PMID- 23122958
TI  - Monoacylglycerol lipase is a therapeutic target for Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common cause of dementia among older people.
      There are no effective medications currently available to prevent and treat AD
      and halt disease progression. Monoacylglycerol lipase (MAGL) is the primary
      enzyme metabolizing the endocannabinoid 2-arachidonoylglycerol in the brain. We
      show here that inactivation of MAGL robustly suppressed production and
      accumulation of beta-amyloid (Abeta) associated with reduced expression of beta
      site amyloid precursor protein cleaving enzyme 1 (BACE1) in a mouse model of AD.
      MAGL inhibition also prevented neuroinflammation, decreased neurodegeneration,
      maintained integrity of hippocampal synaptic structure and function, and improved
      long-term synaptic plasticity, spatial learning, and memory in AD animals.
      Although the molecular mechanisms underlying the beneficial effects produced by
      MAGL inhibition remain to be determined, our results suggest that MAGL, which
      regulates endocannabinoid and prostaglandin signaling, contributes to
      pathogenesis and neuropathology of AD, and thus is a promising therapeutic target
      for the prevention and treatment of AD.

PMID- 23122959
TI  - Normal spastin gene dosage is specifically required for axon regeneration.
AB  - Axon regeneration allows neurons to repair circuits after trauma; however, most
      of the molecular players in this process remain to be identified. Given that
      microtubule rearrangements have been observed in injured neurons, we tested
      whether microtubule-severing proteins might play a role in axon regeneration. We
      found that axon regeneration is extremely sensitive to levels of the microtubule
      severing protein spastin. Although microtubule behavior in uninjured neurons was
      not perturbed in animals heterozygous for a spastin null allele, axon
      regeneration was severely disrupted in this background. Two types of axon
      regeneration-regeneration of an axon from a dendrite after proximal axotomy and
      regeneration of an axon from the stump after distal axotomy-were defective in
      Drosophila with one mutant copy of the spastin gene. Other types of axon and
      dendrite outgrowth, including regrowth of dendrites after pruning, were normal in
      heterozygotes. We conclude that regenerative axon growth is uniquely sensitive to
      spastin gene dosage.

PMID- 23122962
TI  - Cdk11-cyclinL controls the assembly of the RNA polymerase II mediator complex.
AB  - The large Mediator (L-Mediator) is a general coactivator of RNA polymerase II
      transcription and is formed by the reversible association of the small Mediator
      (S-Mediator) and the kinase-module-harboring Cdk8. It is not known how the kinase
      module association/dissociation is regulated. We describe the fission yeast Cdk11
      L-type cyclin pombe (Lcp1) complex and show that its inactivation alters the
      global expression profile in a manner very similar to that of mutations of the
      kinase module. Cdk11 is broadly distributed onto chromatin and phosphorylates the
      Med27 and Med4 Mediator subunits on conserved residues. The association of the
      kinase module and the S-Mediator is strongly decreased by the inactivation of
      either Cdk11 or the mutation of its target residues on the Mediator. These
      results show that Cdk11-Lcp1 regulates the association of the kinase module and
      the S-Mediator to form the L-Mediator complex.

PMID- 23122961
TI  - Targeting of XJB-5-131 to mitochondria suppresses oxidative DNA damage and motor
      decline in a mouse model of Huntington's disease.
AB  - Oxidative damage and mitochondrial dysfunction are implicated in aging and age
      related neurodegenerative diseases, including Huntington's disease (HD). Many
      naturally occurring antioxidants have been tested for their ability to correct
      for deleterious effects of reactive oxygen species, but often they lack
      specificity, are tissue variable, and have marginal efficacy in human clinical
      trials. To increase specificity and efficacy, we have designed a synthetic
      antioxidant, XJB-5-131, to target mitochondria. We demonstrate in a mouse model
      of HD that XJB-5-131 has remarkably beneficial effects. XJB-5-131 reduces
      oxidative damage to mitochondrial DNA, maintains mitochondrial DNA copy number,
      suppresses motor decline and weight loss, enhances neuronal survival, and
      improves mitochondrial function. The findings poise XJB-5-131 as a promising
      therapeutic compound.

PMID- 23122960
TI  - Presenilin deficiency or lysosomal inhibition enhances Wnt signaling through
      relocalization of GSK3 to the late-endosomal compartment.
AB  - Sustained canonical Wnt signaling requires the inhibition of glycogen synthase
      kinase 3 (GSK3) activity by sequestration of GSK3 inside multivesicular endosomes
      (MVEs). Here, we show that Wnt signaling is increased by the lysosomal inhibitor
      chloroquine, which causes accumulation of MVEs. A similar MVE expansion and
      increased Wnt responsiveness was found in cells deficient in presenilin, a
      protein associated with Alzheimer's disease. The Wnt-enhancing effects were
      entirely dependent on the functional endosomal sorting complex required for
      transport (ESCRT), which is needed for the formation of intraluminal vesicles in
      MVEs. We suggest that accumulation of late endosomal structures leads to enhanced
      canonical Wnt signaling through increased Wnt-receptor/GSK3 sequestration. The
      decrease in GSK3 cytosolic activity stabilized cytoplasmic GSK3 substrates such
      as beta-catenin, the microtubule-associated protein Tau, and other proteins.
      These results underscore the importance of the endosomal pathway in canonical Wnt
      signaling and reveal a mechanism for regulation of Wnt signaling by presenilin
      deficiency.

PMID- 23122963
TI  - Transcriptional elongation factor elongin A regulates retinoic acid-induced gene
      expression during neuronal differentiation.
AB  - Elongin A increases the rate of RNA polymerase II (pol II) transcript elongation
      by suppressing transient pausing by the enzyme. Elongin A also acts as a
      component of a cullin-RING ligase that can target stalled pol II for
      ubiquitylation and proteasome-dependent degradation. It is not known whether
      these activities of Elongin A are functionally interdependent in vivo. Here, we
      demonstrate that Elongin A-deficient (Elongin A(-/-)) embryos exhibit
      abnormalities in the formation of both cranial and spinal nerves and that Elongin
      A(-/-) embryonic stem cells (ESCs) show a markedly decreased capacity to
      differentiate into neurons. Moreover, we identify Elongin A mutations that
      selectively inactivate one or the other of the aforementioned activities and show
      that mutants that retain the elongation stimulatory, but not pol II
      ubiquitylation, activity of Elongin A rescue neuronal differentiation and support
      retinoic acid-induced upregulation of a subset of neurogenesis-related genes in
      Elongin A(-/-) ESCs.

PMID- 23122964
TI  - Cyclin A2 is required for sister chromatid segregation, but not separase control,
      in mouse oocyte meiosis.
AB  - In meiosis, two specialized cell divisions allow the separation of paired
      chromosomes first, then of sister chromatids. Separase removes the cohesin
      complex holding sister chromatids together in a stepwise manner from chromosome
      arms in meiosis I, then from the centromere region in meiosis II. Using mouse
      oocytes, our study reveals that cyclin A2 promotes entry into meiosis, as well as
      an additional unexpected role; namely, its requirement for separase-dependent
      sister chromatid separation in meiosis II. Untimely cyclin A2-associated kinase
      activity in meiosis I leads to precocious sister separation, whereas inhibition
      of cyclin A2 in meiosis II prevents it. Accordingly, endogenous cyclin A is
      localized to kinetochores throughout meiosis II, but not in anaphase I.
      Additionally, we found that cyclin B1, but not cyclin A2, inhibits separase in
      meiosis I. These findings indicate that separase-dependent cohesin removal is
      differentially regulated by cyclin B1 and A2 in mammalian meiosis.

PMID- 23122965
TI  - Magnetic resonance enterography in Crohn's disease: a guide to common imaging
      manifestations for the IBD physician.
AB  - Patients with Crohn's disease (CD) frequently require cross-sectional imaging.
      Magnetic resonance enterography (MRE) is an accurate tool for assessment of bowel
      disease and of various complications of CD. The lack of non-ionizing radiation
      exposure is an important advantage of this imaging modality. Familiarity with
      common and pathognomonic imaging features of CD is essential for every clinician
      that is involved in inflammatory bowel disease (IBD) patients' care. This review
      is aimed to describe the indications for performing MRE in CD, essentials of MRE
      techniques and typical radiological findings in patients with CD to aid the IBD
      doctor in daily practice. 

PMID- 23122966
TI  - Pediatric reference intervals for four serum bone markers using two automated
      immunoassays.

PMID- 23122967
TI  - Enzymatic assessment of paraoxonase 1 activity on HDL subclasses: a practical
      zymogram method to assess HDL function.
AB  - BACKGROUND: We developed a practical method for analysis of PON-1 enzymatic
      activity in HDL subclasses. METHODS: The assay uses 4-12% polyacrylamide gradient
      gels, phenylacetate as substrate coupled with densitometric phenol detection
      using 4-aminoantipyrine. The measurement PON-1 activity in situ across the HDL
      subclasses has a strong correlation with the kinetic microplate assay for total
      PON-1 activity, r=0.91, p<0.001. RESULTS: The same HDL-C level, healthy subjects
      (n=33) display a large difference in the ratio of PON-1 activity in small vs.
      large HDL. Since PON-1 activity is larger in HDL(3) we propose that this
      difference has a potent predictive value for clinical risk assessment and
      therapeutic choice. Our method also offers the advantage of assessing the
      distribution of up to six different HDL apolipoproteins in the same gel after
      transfer. CONCLUSIONS: We seek to further dissect the cause of a different
      distribution of PON-1 activity in HDL subclasses by employing this method that
      permits practical, inexpensive analysis of antioxidant function of HDL subclasses
      and has the potential for application in clinical chemistry and to shed some
      light on the importance of PON-1 distribution.

PMID- 23122968
TI  - 20 MHz forward-imaging single-element beam steering with an internal rotating
      variable-angle reflecting surface: Wire phantom and ex vivo pilot study.
AB  - Feasibility is demonstrated for a forward-imaging beam steering system involving
      a single-element 20MHz angled-face acoustic transducer combined with an internal
      rotating variable-angle reflecting surface (VARS). Rotation of the VARS
      structure, for a fixed position of the transducer, generates a 2-D angular sector
      scan. If these VARS revolutions were to be accompanied by successive rotations of
      the single-element transducer, 3-D imaging would be achieved. In the design of
      this device, a single-element 20MHz PMN-PT press-focused angled-face transducer
      is focused on the circle of midpoints of a micro-machined VARS within the distal
      end of an endoscope. The 2-D imaging system was tested in water bath experiments
      with phantom wire structures at a depth of 10mm, and exhibited an axial
      resolution of 66MUm and a lateral resolution of 520MUm. Chirp coded excitation
      was used to enhance the signal-to-noise ratio, and to increase the depth of
      penetration. Images of an ex vivo cow eye were obtained. This VARS-based approach
      offers a novel forward-looking beam-steering method, which could be useful in
      intra-cavity imaging.

PMID- 23122969
TI  - "Headache and epilepsy"--how are they connected?
AB  - The relationship between headache and seizures is a complicated one, since these
      two conditions are related in numerous ways. Although the nature of this
      association is unclear, several plausible explanations exist: the two disorders
      coexist by chance; headache is part (or even the sole ictal phenomenon) of
      seizures or the post-ictal state; both disorders share a common underlying
      etiology; and epilepsy mimics the symptoms of migraine (as in benign childhood
      epilepsy). Seizures and headaches as well as their respective primary syndromes
      (epilepsy and headache/migraine) share several pathophysiological mechanisms.
      These mechanisms especially involve neurotransmitter and ion channel
      dysfunctions. Also, photosensitivity seems to play a role in the connection. In
      order to improve the care for patients with a clinical connection between
      migraine and epilepsy, it is necessary to try to understand more accurately the
      exact pathophysiological point of connection between these two conditions. Both
      experimental and clinical measures are required to better understand this
      relationship. The development of animal models, molecular studies defining more
      precise genotype/phenotype correlations, and multicenter clinical studies with
      revision of clinical criteria for headache/epilepsy-related disorders represent
      the start for planning future translational research. In this paper, we review
      the relationship between migraine and epilepsy in terms of epidemiology and
      pathophysiology with regard to translational research and clinical correlations
      and classification.

PMID- 23122970
TI  - Reply to "Reference values in concentric needle electrode studies".

PMID- 23122971
TI  - Cervical vestibular evoked myogenic potentials in primary headache disorders.
AB  - OBJECTIVE: To determine if cervical vestibular evoked myogenic potentials
      (cVEMPS) differ in patients with migraine without aura (MoA), vestibular migraine
      (VM) and tension type headache (TTH). METHODS: Twenty patients with MoA, 24
      patients with VM and 20 patients with TTH were included in the study. Thirty
      healthy volunteers of comparable age and gender were taken as the control group.
      The latencies of peaks p13 and n23, peak-to-peak amplitude of p13-n23 divided by
      a mean prestimulus EMG recorded during cVEMP testing were measured. The amplitude
      asymmetry between right and left sides was also calculated and taken into
      consideration. Caloric testing was conducted to check if the results are
      associated with the results of the cVEMPs. RESULTS: Five (one on the right, four
      on the left side) of the 24 patients with VM (20.8%) displayed a unilateral
      caloric hypofunction. Normal results were recorded from patients with MoA and
      TTH. p13, n23 latencies and amplitudes of the patient groups were not
      statistically different from the results of the healthy controls (p>0.05). An
      amplitude asymmetry between right and left sides exceeding that of the healthy
      controls was not also present (p>0.05). CONCLUSIONS: Though a hypofunctioning
      horizontal semicircular canal was detected in 20.8% of the patients with VM,
      saccular function seemed to be unaffected. Patients with MoA and TTH did not
      display any vestibular test abnormality. SIGNIFICANCE: Primary headache disorders
      seem to be associated with a normal interictal cVEMP profile.

PMID- 23122972
TI  - Insulin glargine dosing before next-day surgery: comparing three strategies.
AB  - STUDY OBJECTIVE: To evaluate three evening insulin glargine dosing strategies for
      achievement of target (100-179 mg/dL; 5.5 - 9.8 mmol/L) and widened (80-249
      mg/dL; 4.4 - 13.7 mmol/L) preoperative fasting blood glucose (FBG) ranges on the
      day of surgery. DESIGN: Prospective, randomized, open trial. SETTING:
      Preoperative units at two sites of a suburban hospital system. PATIENTS: 401
      adult, ASA physical status 3 and 4 patients with type 1 and type 2 diabetes,
      undergoing elective noncardiac surgery. INTERVENTIONS: Patients were divided into
      two groups according to absence of daily rapid-acting/short-acting insulin
      (insulin glargine-only group) or presence of daily rapid-acting/short-acting
      insulin (insulin glargine plus bolus group). Subjects were then randomized to
      three evening insulin glargine dosing strategies: (a) take 80% of usual dose, (b)
      call physician for dose, or (c) refer to dosing table, based on self-reported
      usual FBG and insulin regimen. In the prehospital setting, patients administered
      the instructed insulin glargine dose on the evening before surgery. MEASUREMENTS:
      Venous blood glucose values were recorded in the preoperative holding area on the
      day of surgery. MAIN RESULTS: No significant differences in target preoperative
      FBG achievement were detected among strategies in the insulin glargine-only group
      (n = 174) or the insulin glargine plus bolus group (n = 227). In widened
      preoperative FBG achievement, no significant difference was noted among
      strategies in the insulin glargine-only group. In the insulin glargine plus bolus
      group, fewer subjects following the dosing table had FBG > 249 mg/dL (> 13.7
      mmol/L; P = 0.031). CONCLUSIONS: Target preoperative FBG achievement was similar
      among strategies in both insulin glargine groups. An insulin glargine adjustment
      strategy based on usual glycemic control may better prevent severe preoperative
      hyperglycemia in patients receiving basal/bolus regimens.

PMID- 23122973
TI  - Is muscle relaxant necessary in patients undergoing laparoscopic gynecological
      surgery with a ProSeal LMATM?
AB  - STUDY OBJECTIVE: To test the hypothesis that muscle relaxant is not necessary in
      patients who are undergoing laparoscopic gynecological surgery with a ProSeal
      Laryngeal Mask Airway (ProSeal LMATM). DESIGN: Prospective, randomized study.
      SETTING: Operating room of Sichuan Provincial Hospital for Women and Children.
      PATIENTS: 120 adult, ASA physical status 1 and 2 women, aged 18 to 55 years.
      INTERVENTIONS AND MEASUREMENTS: Patients were randomly assigned to two groups
      (n=60) to receive a muscle relaxant (Group MR) or not (Group NMR). General
      anesthesia was used in patients of both groups for airway management with the
      ProSeal LMA. Peak airway inflation pressures, airway sealing pressure, minimum
      flow rate, and recovery time were assessed. Surgical conditions were assessed by
      the operating gynecologist. The frequency of sore throats was recorded. MAIN
      RESULTS: ProSeal LMA insertion was 100% successful. Patients' lungs were
      ventilated with a maximum sealing pressure of 32 +/- 5.1 cm H(2)O (Group MR) or
      31 +/- 4.9 cm H(2)O (Group NMR) (P = 0.341). The seal quality in both groups
      permitted the use of low flows: 485 +/- 291 mL/min in Group MR and 539 +/- 344
      mL/min in Group NMR (P = 0.2). Surgical conditions were comparable between the
      two groups. There was no difference in the frequency of sore throats (20% vs
      21.7%; P = 0.28). In Group NMR, there was a statistically significant reduction
      in recovery time versus Group MR (4.5 +/- 2.6 min vs 10.3 +/- 4.2 min; P < 0.01).
      CONCLUSION: Muscle relaxant is not necessary in general anesthesia with a ProSeal
      LMA.

PMID- 23122974
TI  - The effect of a continuous infusion of low-dose esmolol on the requirement for
      remifentanil during laparoscopic gynecologic surgery.
AB  - STUDY OBJECTIVE: To investigate whether a continuous infusion of low-dose esmolol
      results in an opioid-sparing effect during surgery. DESIGN: Randomized, double
      blinded, placebo-controlled clinical comparison study. SETTING: Operating room of
      a university hospital. PATIENTS: 56 ASA physical status 1 and 2 patients, aged 20
      to 60 years, undergoing laparoscopic gynecologic surgery of less than two hours'
      duration. INTERVENTIONS: The esmolol group (n = 28) received a 0.5 mg/kg loading
      dose of esmolol followed by an infusion of esmolol 30 MUg/kg/min; the saline
      group (n = 28) received equivalent volumes of normal saline. MEASUREMENTS: The
      effect-site concentration of remifentanil (ng/mL) to maintain adequate anesthetic
      depth before infusion of the study drug (before-concentration) was measured.
      During infusion of study drug, the effect-site concentration of remifentanil was
      adjusted every 5 minutes to maintain systolic blood pressure within 15% of
      baseline and a Bispectral Index value between 50-60. The average of these
      adjusted concentrations (after-concentration) was measured and compared to the
      before-concentration. The quality of postoperative recovery was assessed. MAIN
      RESULTS: In the esmolol group, the after-concentration of remifentanil was
      decreased by 33.3% compared with the before-concentration. The total dose of
      remifentanil infused was also lower in the esmolol group (0.09 +/- 0.1 vs 0.14 +/
      0.03 MUg/kg/min; P = 0.031). The esmolol group had lower scores on a pain
      numerical rating scale and required less fentanyl in the Postanesthesia Care
      Unit. CONCLUSIONS: Intraoperative esmolol infusion decreases both the requirement
      for remifentanil and postoperative administration of rescue analgesics.

PMID- 23122975
TI  - The ProSeal Laryngeal Mask Airway is more effective than the LMA-Classic in
      pediatric anesthesia: a meta-analysis.
AB  - STUDY OBJECTIVE: To determine, in pediatric patients, whether the ProSeal
      Laryngeal Mask Airway (PLMA) has advantages over the LMA-Classic (cLMA) in leak
      pressure, placement difficulty, incidence of adverse events, postoperative blood
      staining, laryngospasm, bronchospasm, and hoarseness. DESIGN: Meta-analysis.
      SETTING: Metropolitan university medical center. MEASUREMENTS: MEDLINE (1966
      2011), EMBASE (1980-2011), and the CENTRAL (1977-2011) databases was searched for
      randomized controlled trials (RCTs). The relative risk (RR), mean difference
      (MD), and corresponding 95% confidence intervals (CIs) were calculated using
      RevMan 5 statistical software for dichotomous and continuous outcomes,
      respectively. MAIN RESULTS: Of the 13 RCTs that met study inclusion criteria, 8
      trials comprising 557 patients were analyzed. Leak pressure was higher in the
      PLMA (RR = 5.02, 95% CI = 3.64, 6.4). The difference in rate of successful
      placement on the first attempt did not differ between the two devices (RR = 1.00,
      95% CI = 0.94, 1.06). The incidence of gastric insufflation was lower with the
      PLMA (RR = 0.20, 95% CI = 0.07, 0.61). The incidence of postoperative blood
      staining on the mask did not differ (RR = 1.08, 95% CI = 0.52, 2.21), nor was
      there any difference between the two devices in incidence of laryngospasm or
      bronchospasm (RR = 0.75, 95% CI = 0.18, 3.21), or hoarseness (RR = 3.00, 95% CI =
      0.13, 70.83). There was no difference in laryngeal view between the PLMA and cLMA
      (RR = 1.06, 95% CI = 0.90, 1.26). The maximum tidal volume per kg was greater
      with the PLMA (MD = 4.16, 95% CI = 3.56, 4.76). CONCLUSIONS: The PLMA (in sizes
      1,1.5, 2, and 2.5) offers some advantages over the cLMA in pediatric anesthesia.

PMID- 23122976
TI  - A national cross-sectional survey of social networking practices of U.S.
      anesthesiology residency program directors.
AB  - STUDY OBJECTIVE: To determine the social networking practices of directors of
      anesthesiology residency programs. DESIGN: Cross-sectional survey. SETTING:
      Online and paper survey tool. SUBJECTS: 132 anesthesiology residency program
      directors in the United States. MEASUREMENTS: A 13-item survey including
      dichotomous and multiple choice responses was administered using an online survey
      tool and a paper survey. Data analysis was conducted by descriptive and
      analytical statistics (chi-square test). A P-value < 0.05 indicated statistical
      significance. MAIN RESULTS: 50% of anesthesiology program directors responded to
      the survey (66/132). Policies governing social networking practices were in place
      for 30.3% (n=20) of the programs' hospitals. The majority of program directors
      (81.8%, 54) reported never having had an incident involving reprimand of a
      resident or fellow for inappropriate social networking practices. The majority
      (66.7%, n=44) of responding programs reported that departments did not provide
      lectures or educational activities related to appropriate social networking
      practices. Monitoring of social networking habits of residents/fellows by program
      directors mainly occurs if they are alerted to a problem (54.5%, n=36). Frequent
      use of the Internet for conducting searches on a resident applicant was reported
      by 12.1% (n=8) of program directors, 30.3% (n=20) reported use a few times, and
      57.6% (n=38) reported never using the Internet in this capacity. CONCLUSION:
      Residency programs should have a written policy related to social media use.
      Residency program directors should be encouraged to become familiar with the
      professionalism issues related to social media use in order to serve as adequate
      resident mentors within this new and problematic aspect of medical ethics and
      professionalism.

PMID- 23122977
TI  - Insertion/deletion polymorphism of the angiotensin-converting enzyme considerably
      changes postoperative outcome.
AB  - STUDY OBJECTIVE: To evaluate the influence of insertion/deletion (ID)
      polymorphism of the angiotensin-converting enzyme (ACE) gene on clinical outcome
      of cardiac valve surgery. DESIGN: Prospective, blinded observational study.
      SETTING: Operating room and intensive care unit (ICU) of a university hospital.
      PATIENTS: 110 adult patients requiring elective cardiac valve surgery requiring
      cardiopulmonary bypass. MEASUREMENTS: Patients' preoperative data (age, gender,
      body weight, New York Heart Association score, medication, biochemical data, and
      comorbid disorders), anesthetic management (blood pressure, heart rate, blood
      loss and transfusion, and cardiorespiratory complications and their treatment),
      and postoperative outcome (life-threatening complications, nosocomial infections,
      reintubation/reoperation, death, and duration of ICU stay and hospitalization)
      were recorded. ACE ID was detected by gel electrophoresis following conventional
      polymerase chain reaction. Patients were divided into two groups postoperatively;
      groups with II and non-II (ID and DD) genotypes, and group differences were
      analyzed. MAIN RESULTS: Distribution of ACE ID in II, ID, and DD genotypes was
      29%, 59%, and 12%, respectively. The non-II group had significantly greater
      postoperative blood loss and transfusion (P < 0.05), more common postoperative
      infections, and longer ICU stay duration than the II group (P < 0.01).
      CONCLUSIONS: ACE ID polymorphism is associated with a higher incidence of
      postoperative complications, including postoperative infections, in patients
      undergoing cardiac valve surgery.

PMID- 23122978
TI  - Simulation-based driver and vehicle crew training: applications, efficacy and
      future directions.
AB  - Simulation is widely used as a training tool in many domains, and more recently
      the use of vehicle simulation as a tool for driver and vehicle crew training has
      become popular (de Winter et al., 2009; Pradhan et al., 2009). This paper
      presents an overview of how vehicle simulations are currently used to train
      driving-related procedural and higher-order cognitive skills, and team-based
      procedural and non-technical teamwork skills for vehicle crews, and evaluates
      whether there is evidence these training programs are effective. Efficacy was
      evaluated in terms of whether training achieves learning objectives and whether
      the attainment of those objectives enhances real world performance on target
      tasks. It was concluded that while some higher-order cognitive skills training
      programs have been shown to be effective, in general the adoption of simulation
      technology has far outstripped the pace of empirical research in this area. The
      paper concludes with a discussion of the issues that require consideration when
      developing and evaluating vehicle simulations for training purposes - based not
      only on what is known from the vehicle domain, but what can be inferred from
      other domains in which simulation is an established training approach, such as
      aviation (e.g. Jentsch et al., 2011) and medicine (e.g. McGaghie et al., 2010).
      STATEMENT OF RELEVANCE: Simulation has become a popular tool for driver and
      vehicle crew training in civilian and military settings. This review considers
      whether there is evidence that this training method leads to learning and the
      transfer of skills to real world performance. Evidence from other domains, such
      as aviation and medicine, is drawn upon to inform the design and evaluation of
      future vehicle simulation training systems.

PMID- 23122979
TI  - Complex left profunda femoris vein to renal vein bypass for the management of
      progressive chronic iliofemoral occlusion.
AB  - Chronic occlusions of the inferior vena cava (IVC) and iliofemoral veins are long
      term sequelae of deep venous thrombosis (DVT) that can lead to postthrombotic
      syndrome (PTS). Patients may present with a wide spectrum of signs and symptoms,
      ranging from mild discomfort and swelling to severe venous hypertension and
      ulcerations. We report a 68-year-old man who had a history of left lower
      extremity DVT after a laminectomy and who developed PTS with nonhealing ulcers.
      The patient underwent a cross-pubic femorofemoral venous bypass that failed to
      improve his clinical status. After unsuccessful endovascular attempts for
      recanalization of the iliofemoral segment, a profunda femoris to IVC bypass was
      performed. The symptoms recurred 2 years later. Venography revealed restenosis at
      the caval anastomosis that did not resolve by endovascular means. A surgical
      revision was performed, and given the quality of the IVC, a jump bypass was
      created to the left renal vein. The swelling improved and the ulcers healed
      completely. Twenty-eight months after the complex reconstructions, he remains
      ulcer-free with mild edema controlled with stockings. Venous reconstructions
      remain a viable option for patients with symptomatic and recalcitrant
      nonmalignant obstruction of the large veins.

PMID- 23122980
TI  - ExacTrac Snap Verification: a new tool for ensuring quality control for lung
      stereotactic body radiation therapy.
AB  - PURPOSE: The intrafraction verification provided by ExacTrac X-ray 6D Snap
      Verification (ET-SV) allows the tracking of potential isocenter displacements
      throughout patient position and treatment. The aims of this study were (1) to
      measure the intrafraction variations of the isocenter position (random errors);
      (2) to study the amplitude of the variation related to the fraction duration; and
      (3) to assess the impact of the table movement on positioning uncertainties.
      METHODS AND MATERIALS: ET-SV uses images acquired before or during treatment
      delivery or both to detect isocenter displacement. Twenty patients treated with
      stereotactic body radiation therapy (SBRT) for lung tumors underwent SV before or
      during each beam. Noncoplanar beams were sometimes necessary. The time between
      the setup of the patient and each SV was noted, and values of deviations were
      compiled for 3 SV time groups: SV performed at <=10 min (group 1), between 11 and
      20 min (group 2), and >=21 min (group 3). Random errors in positioning during the
      use of noncoplanar fields were noted. RESULTS: The mean isocenter deviation+/-SD
      was 2+/-0.5 mm (range, 1-8 mm). The average deviations+/-SD increased
      significantly from 1.6+/-0.5 mm to 2.1+/-0.8 mm and 2.2+/-0.6 mm for groups 1, 2,
      and 3 (P=.002), respectively. Percentages of deviation>=3 mm were 7.06%, 22.83%,
      and 28.07% and 1.08%, 4.15%, and 8.4% for >=5 mm (P<.0001). For 11 patients,
      table rotation was necessary. The mean isocenter deviation+/-SD increased
      significantly from 1.9+/-0.5 mm before table rotation to 2.7+/-0.5 mm (P=.001)
      for the first beam treated after rotation. CONCLUSIONS: SV detects isocenter
      deviations, which increase in amplitude and frequency with the fraction duration,
      and enables intrafraction verification for SBRT (taking into account clinical
      condition and technical issues). SV gives accurate targeting at any time during
      irradiation and may raise confidence to escalate the dose. SV appears to be an
      important tool for ensuring the quality control of SBRT.

PMID- 23122981
TI  - Replanning during intensity modulated radiation therapy improved quality of life
      in patients with nasopharyngeal carcinoma.
AB  - PURPOSE: Anatomic and dosimetric changes have been reported during intensity
      modulated radiation therapy (IMRT) in patients with nasopharyngeal carcinoma
      (NPC). The purpose of this study was to evaluate the effects of replanning on
      quality of life (QoL) and clinical outcomes during the course of IMRT for NPC
      patients. METHODS AND MATERIALS: Between June 2007 and August 2011, 129 patients
      with NPC were enrolled. Forty-three patients received IMRT without replanning,
      while 86 patients received IMRT replanning after computed tomography (CT) images
      were retaken part way through therapy. Chinese versions of the European
      Organization for Research and Treatment of Cancer Quality of Life Questionnaire
      C30 and Head and Neck Quality of Life Questionnaire 35 were completed before
      treatment began and at the end of treatment and at 1, 3, 6, and 12 months after
      the completion of treatment. Overall survival (OS) data were compared using the
      Kaplan-Meier method. RESULTS: IMRT replanning had a profound impact on the QoL of
      NPC patients, as determined by statistically significant changes in global QoL
      and other QoL scales. Additionally, the clinical outcome comparison indicates
      that replanning during IMRT for NPC significantly improved 2-year local regional
      control (97.2% vs 92.4%, respectively, P=.040) but did not improve 2-year OS
      (89.8% vs 82.2%, respectively, P=.475). CONCLUSIONS: IMRT replanning improves QoL
      as well as local regional control in patients with NPC. Future research is needed
      to determine the criteria for replanning for NPC patients undergoing IMRT.

PMID- 23122983
TI  - Diversity based on race, ethnicity, and sex, of the US radiation oncology
      physician workforce.
AB  - PURPOSE: To assess the current diversity of the US radiation oncology (RO)
      physician workforce by race, ethnicity, and sex. METHODS AND MATERIALS: Publicly
      available American Medical Association, American Association of Medical Colleges,
      and US census registries were used to assess differences by race, ethnicity, and
      sex for 2010 among RO practicing physicians, academic faculty, residents, and
      residency applicants. RO resident diversity was compared to medical school
      graduates and medical oncology (MO) fellows. Significant differences in diversity
      of RO residents by race, ethnicity, and sex were evaluated between 2003 and 2010
      academic years. RESULTS: Females and traditionally underrepresented minorities in
      medicine (URM), blacks, Hispanics, American Indians, Alaska Natives, Native
      Hawaiian, and Pacific Islanders are underrepresented as RO residents (33.3% and
      6.9%, respectively), faculty (23.8%, 8.1%), and practicing physicians (25.5%,
      7.2%) levels compared with the US population (50.8%, 30.0%; P<.01). Although
      females and URMs remain underrepresented at the resident trainee level compared
      with their proportions as medical school graduates (48.3%, 15.6%) and MO fellows
      (45.0%, 10.8%; P<.01), females are significantly increased in proportion as RO
      residents compared with RO practicing physicians (P<.01), whereas representation
      of individual URM groups as RO residents is no different than current practicing
      physicians. There is no trend toward increased diversification for female or URM
      trainees over 8 years, suggesting underrepresentation is not diminishing.
      CONCLUSIONS: Females and URM are underrepresented in the RO physician workforce.
      Given existing cancer disparities, further research and efforts are needed to
      ensure that the field is equipped to meet the needs of an increasingly diverse
      society.

PMID- 23122982
TI  - Validating a prognostic scoring system for postmastectomy locoregional recurrence
      in breast cancer.
AB  - PURPOSE: This study is designed to validate a previously developed locoregional
      recurrence risk (LRR) scoring system and further define which groups of patients
      with breast cancer would benefit from postmastectomy radiation therapy (PMRT).
      METHODS AND MATERIALS: An LRR risk scoring system was developed previously at our
      institution using breast cancer patients initially treated with modified radical
      mastectomy between 1990 and 2001. The LRR score comprised 4 factors: patient age,
      lymphovascular invasion, estrogen receptor negativity, and number of involved
      lymph nodes. We sought to validate the original study by examining a new dataset
      of 1545 patients treated between 2002 and 2007. RESULTS: The 1545 patients were
      scored according to the previously developed criteria: 920 (59.6%) were low risk
      (score 0-1), 493 (31.9%) intermediate risk (score 2-3), and 132 (8.5%) were high
      risk (score >=4). The 5-year locoregional control rates with and without PMRT in
      low-risk, intermediate-risk, and high-risk groups were 98% versus 97% (P=.41),
      97% versus 91% (P=.0005), and 89% versus 50% (P=.0002) respectively. CONCLUSIONS:
      This analysis of an additional 1545 patients treated between 2002 and 2007
      validates our previously reported LRR scoring system and suggests appropriate
      patients for whom PMRT will be beneficial. Independent validation of this scoring
      system by other institutions is recommended.

PMID- 23122984
TI  - Dual-energy micro-computed tomography imaging of radiation-induced vascular
      changes in primary mouse sarcomas.
AB  - PURPOSE: To evaluate the effects of radiation therapy on primary tumor
      vasculature using dual-energy (DE) micro-computed tomography (micro-CT). METHODS
      AND MATERIALS: Primary sarcomas were generated with mutant Kras and p53.
      Unirradiated tumors were compared with tumors irradiated with 20 Gy. A liposomal
      iodinated contrast agent was administered 1 day after treatment, and mice were
      imaged immediately after injection (day 1) and 3 days later (day 4) with DE micro
      CT. CT-derived tumor sizes were used to assess tumor growth. After DE
      decomposition, iodine maps were used to assess tumor fractional blood volume
      (FBV) at day 1 and tumor vascular permeability at day 4. For comparison, tumor
      vascularity and vascular permeability were also evaluated histologically by use
      of CD31 immunofluorescence and fluorescently-labeled dextrans. RESULTS: Radiation
      treatment significantly decreased tumor growth from day 1 to day 4 (P<.05). There
      was a positive correlation between CT measurement of tumor FBV on day 1 and
      extravasated iodine on day 4 with microvascular density (MVD) on day 4
      (R(2)=0.53) and dextran accumulation (R(2)=0.63) on day 4, respectively. Despite
      no change in MVD measured by histology, tumor FBV significantly increased after
      irradiation as measured by DE micro-CT (0.070 vs 0.091, P<.05). Both dextran and
      liposomal-iodine accumulation in tumors increased significantly after
      irradiation, with dextran fractional area increasing 5.2-fold and liposomal
      iodine concentration increasing 4.0-fold. CONCLUSIONS: DE micro-CT is an
      effective tool for noninvasive assessment of vascular changes in primary tumors.
      Tumor blood volume and vascular permeability increased after a single therapeutic
      dose of radiation treatment.

PMID- 23122985
TI  - Reduced hedonic capacity in euthymic bipolar subjects: a trait-like feature?
AB  - BACKGROUND: The aim of our study was to assess hedonic capacity in euthymic
      bipolar subjects, identifying possible differences compared to remitted unipolar
      depressed patients and healthy controls. METHODS: 107 subjects with bipolar
      disorders, 86 with major depressive disorder and 106 healthy controls,
      homogeneous with respect to demographic characteristics, were enrolled. The
      following scales were administered: the Snaith-Hamilton pleasure scale (SHAPS),
      the subscale for 'anhedonia/asociality' of the scale for the assessment of
      negative symptoms (SANS) and the visual analogue scale (VAS) for hedonic
      capacity. RESULTS: Scores on SHAPS total, interests and social interactions, SANS
      'anhedonia/asociality' and VAS were all significantly higher in affective
      disorder patients compared to healthy controls. No difference was found between
      clinical groups. 20.5% (n=22) of bipolar disorder subjects and 24.5% (n=21) of
      major depressed subjects showed a significant reduction in hedonic capacity
      (SHAPS total score >= 3), compared to 7.5% (n=8) of healthy controls
      (chi(2)=12.03; p=.002). LIMITATIONS: Limitations include heterogeneity with
      respect to pharmacological status and longitudinal course (i.e., 'single' vs.
      'recurrent' affective episodes). CONCLUSIONS: The major finding of our study is
      that euthymic bipolar patients and remitted major depressed patients display
      residual anhedonic symptoms. This suggests that, in affective disorder patients,
      altered hedonic capacity could represent an enduring trait and that, possibly,
      dysfunctions in the neurobiological mechanisms underlying hedonic response and
      reward processing persist, irrespective of mood state.

PMID- 23122986
TI  - Towards biological anulus repair: TGF-beta3, FGF-2 and human serum support matrix
      formation by human anulus fibrosus cells.
AB  - Closure and biological repair of anulus fibrosus (AF) defects in intervertebral
      disc diseases is a therapeutic challenge. The aim of our study was to evaluate
      the anabolic properties of bioactive factors on cartilaginous matrix formation by
      AF cells. Human AF cells were harvested from degenerated lumbar AF tissue and
      expanded in monolayer culture. AF cell differentiation and matrix formation was
      initiated by forming pellet cultures and stimulation with hyaluronic acid (HA),
      human serum (HS), fibroblast growth factor-2 (FGF-2), transforming growth factor
      beta3 (TGF-beta3) and TGF-beta3/FGF-2 for up to 4 weeks. Matrix formation was
      assessed histologically by staining of proteoglycan, type I and type II collagens
      and by gene expression analysis of typical extracellular matrix molecules and of
      catabolic matrix metalloproteinases MMP-2 and MMP-13. AF cells, stimulated with
      HS, FGF-2 and most pronounced with TGF-beta3 or TGF-beta3/FGF-2 formed a
      cartilaginous matrix with significantly enhanced expression of matrix molecules
      and of MMP-13. Stimulation of AF cells with TGF-beta3 was accompanied by
      induction of type X collagen, known to occur in hypertrophic cartilage cells
      having mineralizing potential. HA did not show any chondro-inductive
      characteristics. These findings suggest human serum, FGF-2 and TGF-beta3 as
      possible candidates to support biological treatment strategies of AF defects.

PMID- 23122987
TI  - Evaluation of the behavior of murine and human embryonic stem cells in in vitro
      migration and invasion assays.
AB  - Cell migration and invasion are essential processes in a variety of physiological
      events in the body, but also in several patho-physiological events. In this
      paper, the behavior of murine and human embryonic stem cells is examined in in
      vitro migration and invasion models. mESC and hESC were applied as spheroids,
      also known as patches, and as single cells, to mimic possible cell therapy
      application strategies. Two known in vitro migration assays, the ECM
      (extracellular matrix) assay and the Boyden chamber migration assay were
      selected. These assays revealed that mESC are statistically significantly more
      infiltrative than hESC. Application as spheroid results in a slightly higher
      infiltrative capacity compared single cells. The PHF (precultured chick heart
      fragment) assay was selected as an invasion assay. In the PHF assay a more 3D
      examination of the infiltrative nature of the ESC can be observed. The mESC
      showed infiltrative behavior, as spheroids and as single cells. The hESC were
      infiltrative as single cells but not as spheroids. The results of these assays
      are mostly complementary and prove the applicability of these assays, which were
      originally applied in tumor biology, in migratory behavior studies regarding stem
      cells and their progeny in basic and other conditions.

PMID- 23122988
TI  - Influencing factors for saliva urea and its application in chronic kidney
      disease.
AB  - OBJECTIVES: To analyze possible influencing factors on concentration of saliva
      urea (SaU) and to validate its application in chronic kidney disease(CKD). DESIGN
      AND METHODS: Level of SaU in patients and normal subjects was researched.
      RESULTS: The concentration of SaU did not vary with sampling time and genders,
      but was related to ages and level of serum urea (U). CONCLUSION: SaU
      concentration is stable and it is useful in application in CKD.

PMID- 23122989
TI  - [Accidental fatal colchicine overdose].

PMID- 23122990
TI  - [Brain injury secondary to lightning strike].

PMID- 23122991
TI  - First year experience of rotavirus immunisation programme in Finland.
AB  - INTRODUCTION: This study aimed to estimate the impact of rotavirus (RV)
      immunisation programme on the total hospital treated acute gastroenteritis (AGE)
      burden, as well as, on severe RV disease burden in Finland during the first year
      after immunisation programme introduction. Such studies can also be considered as
      a vaccine-probe-study, where unspecific disease burden prevented by immunisation
      is assumed to be caused by the agent the vaccine is targeted against. METHODS:
      The RV related outcome definitions were based on data registered in the National
      Hospital Discharge Register coded using ICD 10 codes. Incidences of hospitalised
      and hospital outpatient cases of AGE and RVGE were compared prior (1999-2005) and
      after (2010) the start of the programme among children under 5 years of age. ICD
      10 codes utilised were A00-A09, R11 and K52. RESULTS: The reductions in disease
      burden, when the post-introduction year was compared to pre-vaccine era, were
      80.3% (95% CI 74.5-84.7) in hospital inpatient RVGE among toddlers less than 1
      year of age and 53.9% (95% CI 49.8-57.7) when the total inpatient AGE burden was
      considered in the same age group. For the corresponding hospital outpatient cases
      the reductions were 78.8% (95% CI 48.4-91.3) and 12.5% (7.1-17.7). The overall
      vaccine impact against confirmed RVGE in age cohorts eligible for vaccination
      before the RV season 2010 was 97% (95% CI 90.7-99.0). If the total reductions,
      both in diagnosed RVGE, as well as in cases without definite microbial diagnosis,
      were expected to be RVGE, population based estimates for the total disease burden
      can be obtained: for inpatient RVGE in children less than 1 year of age the
      estimate is 10.5/1000 pyrs, while the diagnosed specific incidence was less than
      half of that, 4.9/1000 pyrs. DISCUSSION: During the first post-vaccination year
      2010, RV immunisation programme clearly managed to control the severe, hospital
      treated, forms of RVGE. The total disease burden is a more valuable end point
      than mere diagnosed cases as laboratory confirmation practises change after
      vaccine introduction. Our study is limited by the very short post-introduction
      follow up.

PMID- 23122992
TI  - Subacromial bursitis following human papilloma virus vaccine misinjection.
AB  - A patient presented at our clinic with severe subacromial bursitis, which
      persisted for several months following a third booster injection with CervarixTM.
      Chronic subacromial bursitis manifested itself in this patient after what
      appeared to be the misinjection of vaccine in close proximity to the acromion.
      This bursitis was resistant to conventional physiotherapy and to corticosteroid
      therapy, but was responsive to arthroscopic surgery. Since such patients may
      present to an arthroscopic surgeon only months after receiving a vaccine
      injection, this etiological link may not be fully appreciated by treating
      clinicians. Further, the accuracy of injection in the deltoid region also appears
      under appreciated, and this report highlights the importance of accurate
      injection to the deltoid region or in certain cases, the value of simply changing
      the injection site to another larger muscle.

PMID- 23122993
TI  - Cell-wall preparation containing poly-gamma-D-glutamate covalently linked to
      peptidoglycan, a straightforward extractable molecule, protects mice against
      experimental anthrax infection.
AB  - Bacillus anthracis is the causative agent of anthrax that is characterized by
      septicemia and toxemia. Many vaccine strategies were described to counteract
      anthrax infection. In contrast with veterinary live vaccines, currently human
      vaccines are acellular with the protective antigen, a toxin component, as the
      main constituent. However, in animal models this vaccine is less efficient than
      the live vaccine. In this study, we analyzed the protection afforded by a single
      extractable surface element. The poly-gamma-D-glutamate capsule is covalently
      linked to the peptidoglycan. A preparation of peptidoglycan-linked poly-gamma-D
      glutamate (GluPG) was tested for its immunogenicity and its protective effect.
      GluPG injection, in mice, elicited the production of specific antibodies directed
      against poly-glutamate and partially protected the animals against lethal
      challenges with a non-toxinogenic strain. When combined to protective antigen,
      GluPG immunization conferred full protection against cutaneous anthrax induced
      with a fully virulent strain.

PMID- 23122994
TI  - Integrating Leonardo da Vinci's principle of curiosity in contemporary nursing
      education.

PMID- 23122995
TI  - Investigation of the ultrasound effect and target analyte selectivity of
      dispersive liquid-liquid microextraction and its application to a quinocetone
      pharmacokinetic study.
AB  - An ultrasound-assisted dispersive liquid-liquid microextraction (UADLLME) was
      developed as a simple, sensitive, and robust method for the simultaneous
      determination of quinocetone (QCT) and three of its synthesized desoxy
      metabolites in swine urine samples via high-performance liquid chromatography
      (HPLC). Experimental parameters were optimized using the one-factor-at-a-time
      approach and were followed using an orthogonal array design. The results indicate
      that ultrasonic irradiation significantly affects the DLLME extraction
      efficiency. Moreover, the intermolecular binding energies and octanol-water
      partition ratio (K(ow)) of the target analytes were calculated using the density
      functional theory and the atom-additive method, respectively. A high correlation
      was found between the extraction efficiency and the calculated results, which may
      serve as a scientific guideline in the determination of the target analyte
      selectivity of DLLME. The feasibility of UADLLME with HPLC for the simultaneous
      determination of QCT and its desoxy metabolites in blank swine urine samples was
      then investigated. Higher enrichment factors (118-175), low limits of detection
      (0.06-0.12 ng mL(-1)), and high precisions (relative standard deviation < 2.5%)
      were obtained. Calibration curves were performed in the 0.5-500 ng mL(-1) range
      and displayed good linearity. In addition, the proposed method was successfully
      applied to the pharmacokinetic study of QCT and its desoxy metabolites in real
      urine samples. The results show that UADLLME has a potential application in the
      pharmacokinetic and residue studies of quinoxaline-N-dioxides derivatives in
      biological fluid samples.

PMID- 23122996
TI  - Health related quality of life, reoperation rate and function in patients with
      diabetes mellitus and hip fracture--a 2 year follow-up study.
AB  - INTRODUCTION: Diabetes mellitus confers an increased risk of hip fractures. There
      is a limited knowledge of how the outcome after a hip fracture in patients with
      diabetes affect Health Related Quality of Life (HRQoL). The primary aim of this
      study was to evaluate HRQoL. Secondary aims were reoperation rate, complications
      and functions in patients with diabetes followed for 2 years after a hip
      fracture. MATERIALS AND METHODS: Out of 2133 patients diabetes was present in 234
      patients (11%). Main outcome measurements were HRQoL evaluated with EuroQoL 5
      Dindex score, reoperation rate, surgical and medical complications, function as
      walking ability, daily activities, living condition and pain. RESULTS:
      Preoperatively, patients with diabetes mellitus had more pain (p=0.044), co
      morbidities, reduced health status (p=0.001) and more often used a walking frame
      (p=0.014) than patients without diabetes, whereas Katz ADL index, cognition and
      body mass index did not differ. There was no difference in fracture type,
      surgical method or reoperation between the two groups or between patients with
      insulin treated or oral treated diabetes. The EQ-5Dindex score decreased from
      0.64 at admission to 0.45 at 4 months, 0.49 at 12 months and 0.51 at 24 months
      with similar results for patients with and without diabetes. During the first
      postoperative year there was not more medical complications among patients with
      diabetes, however cardiac (p=0.023) and renal failure (p=0.032) were more
      frequent in patients with diabetes at 24 months. Patients with diabetes more
      often had severe hip pain at 4 months (p=0.031). At 12 months more diabetic
      patients were living independently (p=0.034). There was no difference in walking
      ability, ADL and living condition between the groups at 24 months. CONCLUSION:
      The findings of this study indicate that patients with diabetes mellitus had more
      pain, co-morbidities, reduced health status preoperatively than patients without
      diabetes. Hip fracture patients with diabetes mellitus have more hip pain at 4
      months. Cardiac and renal failure was more frequent in patients with diabetes at
      24 months but otherwise we found a comparable re-operation rate, function and
      deterioration of Health Related Quality of Life as patients without diabetes
      within 2 years after a hip fracture.

PMID- 23122997
TI  - Epidemiological patterns and preventability of traumatic hand amputations among
      adults in Greece.
AB  - INTRODUCTION: Hand/finger amputations though rare account for significant
      disability and health-related costs; yet, information on underlying causes,
      springing mostly from physicians' reports, is rather anecdotal. We sought to draw
      attention to the high preventable fraction of hand/finger amputations among
      adults in Greece. PATIENTS AND METHODS: Data on external cause of injury and
      short-term outcome, recorded over nine years in the Emergency Department Injury
      Surveillance System (EDISS) were analysed, whereas sample weights were used for
      nationwide extrapolations. RESULTS: Hand/finger injuries accounted for 20.4% (N =
      57,986) among 284,705 injuries recorded in patients >14-year-old (3% annual
      probability); 728 (1.3%) resulted in amputations; the estimated incidence rate
      (IR) was 39.3/100,000 person-years, reaching a high 92.6/100,000 among males aged
      45-64 years. As expected, the vast majority of victims were males (90%),
      frequently young immigrants; ~two-thirds sustained occupational injuries during
      working hours. Objects most frequently involved included: machinery (57%
      overall/69% occupational), means of transport (10.4%), materials (9.5%), parts of
      buildings/furniture (5%). Wood-working was the most common risk factor (20%
      overall/28% occupational) whereas 6% of victims accepted own inattention. 30% of
      amputations were hospitalised whereas 10% transferred to specialised units.
      DISCUSSION: Specialised registries reveal the magnitude and specific causes of
      disabling hand injuries and point to tailored national injury prevention
      programs; specifically in Greece, as they occur in more controlled occupational
      environments among middle-aged males, woodworkers, and are caused mainly by
      machinery. CONCLUSIONS: Increased management of safety in the workplace could
      play a role in reduction in hand amputations.

PMID- 23122998
TI  - Predictive capacity of pain beliefs and catastrophizing in Whiplash Associated
      Disorder.
AB  - INTRODUCTION: Beliefs about pain are known to be important factors in recovery,
      most notably in LBP. Relatively less is known about the role of pain beliefs in
      Whiplash Associated Disorder (WAD). The widely advocated cognitive-behavioural
      approach to pain management necessitates cognitive factors such as pain beliefs
      be examined, even early after injury. The primary purpose of this study was to
      explore the predictive capacity of early post-injury pain beliefs and
      catastrophizing in patients with WAD. METHODS: Patients (n=72) undergoing
      treatment for acute WAD in physical therapy and chiropractic clinics were invited
      to participate in the study. Research participants were asked to complete
      measures of beliefs (Survey of Pain Attitudes (SOPA) and Pain Beliefs and
      Perception Inventory (PBPI)) and catastrophizing (Pain Catastrophizing Scale) at
      baseline (within 6 weeks of injury), and 3 and 6 months post-injury. In addition,
      pain severity and self-reported disability using the Whiplash Disability
      Questionnaire (WDQ) were recorded at each measurement occasion. Baseline belief
      and catastrophizing scores were examined for their relationship with future pain
      and disability using multiple linear regression. RESULTS: Expectancy beliefs
      (PBPI Permanence and SOPA Medical Cure) were negatively correlated with pain
      intensity at 6-months and uniquely accounted for 16% and 14% of explained
      variance, respectively, after controlling for baseline pain intensity, age, sex
      and history of WAD. Consistent with previous research, catastrophizing was also
      found to be predictive of future pain. The amount of unique variance explained by
      beliefs in the prediction of future disability was modest after controlling for
      baseline disability, age, sex and history of WAD. DISCUSSION: These results
      suggest that expectancy beliefs are potentially important constructs to include
      in future explanatory prognosis studies. The Medical Cure and Permanence
      subscales of the SOPA and PBPI are tools that could be used to measure these
      expectancy constructs.

PMID- 23122999
TI  - First successful complete replantation of a traumatic hemipelvectomy: follow-up
      after 30 months.
AB  - Traumatic hemipelvectomy is a severe, however rare injury associated with high
      lethality. Up to now, immediate surgical completion of the amputation has been
      recommended as a lifesaving therapy. We present a case of near complete
      hemipelvectomy with open fracture of the ileosacral joint, wide open symphysis
      and severe soft tissue trauma including a decollement around the pelvis.
      Successful complete replantation was performed by primary internal stabilisation
      and revascularisation using vascular grafts. In the further hospital course,
      numerous revisions of the soft tissue injury and reconstructive surgery were
      needed. Thirty months later, the patient's condition is physically and
      psychologically stable and he is able to walk using crutches. The key point of
      successful management was skilled emergency damage control surgery followed by
      dedicated surgical care to avoid septic complications. 

PMID- 23123000
TI  - Patterns of CT use and surgical intervention in upper limb periarticular
      fractures at a level-1 trauma centre.
AB  - OBJECTIVES: The universal availability of CT scanners has led to lower thresholds
      for imaging despite significant financial costs and radiation exposure. We
      hypothesised that this recent trend has increased the use of CT for upper limb
      periarticular fractures and led to more frequent operative management. METHOD: A
      5-year retrospective study (01/07/2005-30/06/2010) was performed on all adult
      patients with upper extremity periarticular fractures (OTA: 11, 13, 21 and 23)
      admitted to a level-1 trauma centre. Patients were identified from the
      institution's prospectively maintained OTA classification database. RESULTS: A
      total of 1734 upper extremity periarticular fractures were identified in 1651
      patients. 65% (1132/1734) were operated on. 32% (557/1734) had CT imaging and 78%
      (431/557) of these had operative management. CT use for all fractures and ages
      showed no change (0.56%/year, p = 0.210, r(2) = 0.457). Operative intervention
      increased at a rate of 2.17%/year (p = 0.004, r(2) = 0.959). Within each fracture
      type, CT rates showed no change. Operative management of proximal humerus and
      distal radius fractures became more frequent (6.30%/year, p = 0.002, r(2) = 0.969
      and 0.96%/year, p = 0.046, r(2) = 0.784 respectively). Fractures around the elbow
      showed no change. In patients younger than 55 years, only proximal humerus
      fractures had more frequent imaging (3.17%/year, p = 0.023, r(2) = 0.866). In
      patients over 55 the frequency of CT scanning did not increase, but they were
      more frequently operated on (4.09%/year, p = 0.012, r(2) = 0.907). In older
      patients the rate of surgical intervention increased in all but the distal
      humerus region, Proximal humerus (6.19%/year, p = 0.015, r(2) = 0.894), proximal
      forearm (4.57%/year, p = 0.007, r(2) = 0.931) and distal radius (2.70%/year, p =
      0.002, r(2) = 0.871). CONCLUSION: During the examined 5-year period no increases
      of in CT imaging frequency were observed. The significantly increased number of
      operations among older patients is unlikely to be driven by imaging frequency.

PMID- 23123001
TI  - Clinical overview of dalfampridine: an agent with a novel mechanism of action to
      help with gait disturbances.
AB  - BACKGROUND: Medication used to treat multiple sclerosis (MS) can be categorized
      as disease-modifying therapies, symptomatic therapies, or treatment of acute
      exacerbations. Dalfampridine is the first symptomatic therapy approved by the
      Food and Drug Administration to improve walking in patients with MS. OBJECTIVE:
      This article reviews the pharmacology, pharmacodynamic properties, and
      pharmacokinetic properties of dalfampridine, as well as its clinical efficacy,
      safety profile, pharmacoeconomic considerations, and place in therapy. METHODS:
      Three PubMed searches were conducted for original articles published in English
      between 1966 and August 2012 with human study participants. Articles concerning
      the pharmacology, pharmacokinetic properties, pharmacodynamic properties,
      efficacy, and safety profile of dalfampridine were evaluated. RESULTS:
      Dalfampridine theoretically works to improve conduction and enhance walking by
      inhibiting potassium channels in the axonal membrane and by prolonging action
      potentials in demyelinated neurons. The efficacy of dalfampridine has been
      reported in 2 Phase III clinical trials in patients with MS. When comparing
      dalfampridine 10 mg twice daily with placebo, these studies found a statistically
      significant improvement in walking (42.9% vs 9.3% and 35% vs 8%; P < 0.001).
      However, clinical trials and postmarketing surveillance have shown an increased
      risk of seizures with dalfampridine use that appears to be dose related
      [corrected]. CONCLUSIONS: Dalfampridine has a unique mechanism of action, leading
      to its approval as the first symptomatic therapy for MS to improve walking speed.
      The increased risk of seizures can be a safety concern and will require health
      care providers to be diligent in monitoring patients and to ensure adequate
      patient education [corrected]. The addition of dalfampridine as symptomatic
      therapy for MS may lead to additional novel products in the future.

PMID- 23123002
TI  - Facile fabrication of efficient AgBr-TiO2 nanoheterostructured photocatalyst for
      degrading pollutants and its photogenerated charge transfer mechanism.
AB  - A simple microemulsion-like chemical precipitation method has been successfully
      developed to construct effectively-contacted AgBr-TiO(2) composite. The key of
      this method is the dual roles of Br(-) in the synthetic process, as linkers
      between cetyltrimethyl ammonium cation surfactants and nanocrystalline anatase
      TiO(2) in the acidic condition, and as bromine sources to directly produce
      nanocrystalline AgBr on the surfaces of TiO(2) by chemical precipitation. It is
      well demonstrated that the as-constructed AgBr-TiO(2) nanoheterostructured
      composites display effective photogenerated charge transfer between AgBr and
      TiO(2), favorable to improve charge separation, by means of the surface
      photovoltage technique in different atmospheres at the aid of outer electric
      fields, especially for the transient surface photovoltage technique in air. And
      also, the Br(-) in crystal lattice of AgBr could effectively capture
      photogenerated holes under illumination. These factors are well responsible for
      the enhanced activity for photocatalytic degradation of liquid phase aqueous
      phenol solution and gas phase acetaldehyde under either UV-visible or visible
      irradiation, and the stability of AgBr in the photocatalytic processes.

PMID- 23123003
TI  - Photocatalytic degradation of paracetamol: intermediates and total reaction
      mechanism.
AB  - The advanced oxidation of paracetamol (PAM) promoted by TiO(2)/UV system in
      aqueous medium was investigated. Monitoring this reaction by HPLC and TOC, it was
      demonstrated that while oxidation of paracetamol is quite efficient under these
      conditions, its mineralization is not complete. HPLC indicated the formation of
      hydroquinone, benzoquinone, p-aminophenol and p-nitrophenol in the reaction
      mixtures. Further evidence of p-nitrophenol formation was obtained following the
      reaction by UV-vis spectroscopy. Continuous monitoring by IR spectroscopy
      demonstrated the breaking of the aromatic amide present in PAM and subsequent
      formation of several aromatic intermediate compounds such as p-aminophenol and p
      nitrophenol. These aromatic compounds were eventually converted into trans
      unsaturated carboxylic acids. Based on these experimental results, an alternative
      deacylation mechanism for the photocatalytic oxidation of paracetamol is
      proposed. Our studies also demonstrated IR spectroscopy to be a useful technique
      to investigate oxidative mechanisms of pharmaceutical compounds.

PMID- 23123004
TI  - Implementation of quality assurance and performance improvement programs in
      nursing homes: a brief report.
AB  - The purpose of this article was to investigate nursing homes' (NHs') readiness to
      implement a quality assurance and performance improvement (QAPI) program as
      required by Section 6102 of the Affordable Care Act. Nursing home administrators
      (NHAs) in 3000 NHs (response rate, 67%) were surveyed using a 70-item
      questionnaire to assess: (1) current facility approaches to quality, (2) NHA's
      self-assessed knowledge of QAPI techniques; and (3) the use of QAPI techniques.
      The Online Survey, System for Certification and Administrative Reporting data and
      the Area Resource File were also used to examine and compare facility and market
      characteristics. As rated on a scale of 1 to 10, NHs are more likely to use
      quality assurance (rating, 7.2) and least likely to use total quality management
      (rating, 4.1). Few NHAs use tools for QAPI such as flow charts (23%), Plan-Do
      Check-Act cycles (13%), or run charts (9%). A gap in knowledge of quality
      improvement tools has been identified signifying that the new QAPI regulations
      may pose an issue for NHAs who possibly lack the knowledge and technical
      expertise to implement a comprehensive QAPI program.

PMID- 23123005
TI  - Perspective: Protein supplementation in frail older persons: often necessary but
      not always sufficient.

PMID- 23123006
TI  - Perspective: Protein: what kind, how much, when?

PMID- 23123007
TI  - Clinical outcomes of vertebroplasty or kyphoplasty for patients with vertebral
      compression fractures: a nationwide cohort study.
AB  - OBJECTIVE: To evaluate the outcome of vertebroplasty or kyphoplasty (VK), in
      comparison with non-VK treatment, among patients hospitalized for first-ever
      vertebral compression fractures (VCFs). DESIGN: A population-based retrospective
      cohort study. SETTING: Taiwan' s National Health Insurance claims data.
      PARTICIPANTS: All individuals aged >= 60 years who were newly discharged after
      hospitalization for a primary VCF diagnosis. INTERVENTION: Percutaneous
      vertebroplasty or kyphoplasty. MEASUREMENTS: Study outcomes were discharge
      outcome (re-hospitalization within 1 week, 1 month or 6 months, categorized by
      diagnosis) and the prescription of anti-osteoporosis medication for secondary
      fracture prevention. Potential selection bias was adjusted by using propensity
      score matching to select one conservatively treated patient (e.g. lumbar brace,
      analgesics, or physical therapy) matched to one patient receiving VK. RESULTS:
      The study cohort consisted of 9238 patients who had been discharged after
      hospitalization for a first-ever VCF between 2004 and 2007. During the index
      hospitalization, 1018 patients received VK, compared with 8,220 patients who did
      not receive VK. Patients receiving percutaneous procedure group had a
      consistently lower incidence of 7-day re-hospitalization for any of the three
      outcomes (OR = 0.48; 95% CI: 0.32-0.72). Considering the cause of re
      hospitalization separately, the vertebroplasty/kyphoplasty group had a
      significantly lower risk of 7-day re-hospitalization for fracture-related
      diagnosis (OR = 0.28, 95% CI: 0.12-0.68) and musculoskeletal diagnosis (OR =
      0.08, 95% CI: 0.01-0.88) as well as a significantly lower risk of 1-month re
      hospitalization (OR = 0.74; 95% CI: 0.59-0.93). CONCLUSIONS: VK may protect
      patients with VCFs from short-term re-hospitalization and a greater need exists
      for anti-osteoporosis medication as secondary prevention for this at-risk patient
      group.

PMID- 23123008
TI  - Response to the Letter from Fortington et al.

PMID- 23123009
TI  - Predictors of the time to institutionalization in young- versus late-onset
      dementia: results from the Needs in Young Onset Dementia (NeedYD) study.
AB  - OBJECTIVE: To investigate the time from symptom onset to institutionalization in
      persons with young-onset dementia (YOD) and compare these findings with late
      onset dementia (LOD), and to determine which factors predict institutionalization
      in persons with YOD compared with LOD. DESIGN/SETTING: Longitudinal study of
      community-dwelling patients with YOD and LOD and their caregivers. PARTICIPANTS:
      A total of 226 patients with YOD and 102 with LOD and their informal caregivers
      were recruited through memory clinics and health care facilities. MEASUREMENTS:
      Cox proportional hazard models were used to relate covariates with time to
      institutionalization. The main outcome was time from symptom onset to
      institutionalization. Key predictors were cohort (YOD or LOD), neuropsychiatric
      symptoms, caregiver distress caused by neuropsychiatric symptoms, and caregivers'
      sense of competence (Short Sense of Competence Questionnaire total score).
      RESULTS: The time from symptom onset to institutionalization was nearly 9 years
      for patients with YOD compared with approximately 4 years for patients with LOD.
      In the YOD group, apathy significantly predicted time of institutionalization.
      Furthermore, the caregiver's competence in caring for the person with dementia
      significantly predicted institutionalization in both groups. CONCLUSIONS:
      Patients with YOD are cared for at home for a longer period than patients with
      LOD. The results of this study underline the importance of a timely diagnosis for
      these patients and their families to facilitate the initiation of appropriate
      care and support. Support programs aimed at enhancing the caregivers' sense of
      competence and ability to deal with neuropsychiatric symptoms, especially apathy,
      may postpone the institutionalization of the patient.

PMID- 23123010
TI  - Treatment of restless legs syndrome with a nitroglycerin patch.

PMID- 23123011
TI  - Antigenic characterization of recent H5N1 highly pathogenic avian influenza
      viruses circulating in Egyptian poultry.
AB  - The extensive circulation of Highly Pathogenic (HP) H5N1 Avian Influenza in Egypt
      in poultry since 2006 resulted in the emergence of distinct clades with the
      recent identification of a further clade: 2.2.1.1. The aim of this study was to
      characterize for the first time the antigenic profile of an extensive collection
      of genetically diverse Egyptian H5N1 HP viruses isolated between 2007 and 2010
      applying antigenic cartography and principal component analysis to serological
      data. We identified that Egyptian H5N1 viruses have undergone significant
      antigenic diversification between 2007 and 2010 and two distinct antigenic
      clusters co-circulated in 2010. Such clusters correlated with 2.2.1 and 2.2.1.1
      clades, showing for the first time that the new emerging clade 2.2.1.1 is
      antigenically distinct. This study highlights that the antigenic diversity of
      H5N1 HP Egyptian viruses may represent a potential challenge for the development
      of an effective vaccination programme for animal and human health in Egypt.

PMID- 23123012
TI  - Proteotoxic stress induced by Autographa californica nucleopolyhedrovirus
      infection of Spodoptera frugiperda Sf9 cells.
AB  - Baculovirus AcMNPV causes proteotoxicity in Sf9 cells as revealed by accumulation
      of ubiquitinated proteins and aggresomes in the course of infection. Inhibition
      of proteasomes by lactacystin increased markedly the stock of ubiquitinated
      proteins indicating a primary role of proteasomes in detoxication. The
      proteasomes were present in Sf9 cells as 26S and 20S complexes whose protease
      activity did not change during infection. Proteasome inhibition caused a delay in
      the initiation of viral DNA replication suggesting an important role of
      proteasomes at early stages in infection. However, lactacystin did not affect
      ongoing replication indicating that active proteasomes are not required for
      genome amplification. At late stages in infection (24-48 hpi), aggresomes
      containing the ubiquitinated proteins and HSP/HSC70s showed gradual fusion with
      the vacuole-like structures identified as lysosomes by antibody to cathepsin D.
      This result suggests that lysosomes may assist in protection against
      proteotoxicity caused by baculoviruses absorbing the ubiquitinated proteins.

PMID- 23123013
TI  - Memory of viral infections by CRISPR-Cas adaptive immune systems: acquisition of
      new information.
AB  - Multiple organisms face the threat of viral infections. To combat phage invasion,
      bacteria and archaea have evolved an adaptive mechanism of protection against
      exogenic mobile genetic elements, called CRISPR-Cas. In this defense strategy,
      phage infection is memorized via acquisition of a short invader sequence, called
      a spacer, into the CRISPR locus of the host genome. Upon repeated infection, the
      'vaccinated' host expresses the spacer as a precursor RNA, which is processed
      into a mature CRISPR RNA (crRNA) that guides an endonuclease to the matching
      invader for its ultimate destruction. Recent efforts have uncovered molecular
      details underlying the crRNA biogenesis and interference steps. However, until
      recently the step of adaptation had remained largely uninvestigated. In this
      minireview, we focus on recent publications that have begun to reveal molecular
      insights into the adaptive step of CRISPR-Cas immunity, which is required for the
      development of the heritable memory of the host against viruses.

PMID- 23123014
TI  - Discriminant validity of a new measure of self-efficacy for reaching movements
      after stroke-induced hemiparesis.
AB  - STUDY DESIGN: Case-control study. INTRODUCTION: After stroke, difficulties in
      motor control mediate spontaneous paretic arm use in real life. Along with the
      obvious motor impairments, self-efficacy has been shown to be an important
      modifier for physical function. However, a self-efficacy measure for arm reaching
      is lacking. The aim of this study was to develop such a measure and to examine
      its validity. METHODS: Fifteen participants with hemiparesis and ten control
      participants were recruited. A measure of reaching self-efficacy (RSE) was
      developed using a two-dimensional center-out target array. RESULTS: For the
      control group, RSE was significantly correlated with target distance (r = -0.657)
      and location (r = -0.545), respectively. Additionally, average RSE was lower for
      the non-dominant than the dominant hand (p < 0.001). More importantly, for the
      stroke group, RSE was significantly correlated with target distance (r = -0.603)
      and location (r = -0.378), respectively. Finally, average RSE was lower for the
      paretic than the non-paretic hand (p < 0.001). CONCLUSIONS: These results
      demonstrate robust discriminant validity for this new measure of reaching self
      efficacy. LEVEL OF EVIDENCE: 3b.

PMID- 23123016
TI  - Bicyclic peptidomimetics targeting secreted aspartic protease 2 (SAP2) from
      Candida albicans reveal a constrained inhibitory chemotype.
AB  - The in vitro screening of stereoisomeric bicyclic peptidomimetics towards SAP2 of
      Candida albicans revealed a constrained chemotype as aspartic protease inhibitor
      in the micromolar to nanomolar range. The results indicated that the acetal
      bridge may serve as a transition-state isostere, and that the right match between
      interactions with subsites and the orientation by hydrogen bonding with Gly85 is
      the main requisite for inhibitory activity. Molecular docking calculations
      suggested the bicyclic acetal scaffold to be capable of interacting with the two
      catalytic aspartic acids, thus resulting in good inhibitory activity with only
      two hydrophobic groups addressing the enzyme catalytic subsites.

PMID- 23123015
TI  - Design, synthesis, and evaluation of imidazo[1,2-b]pyridazine derivatives having
      a benzamide unit as novel VEGFR2 kinase inhibitors.
AB  - The vascular endothelial growth factor (VEGF) signaling pathway has been
      implicated in tumor angiogenesis, and inhibition of the VEGF pathway is
      considered an efficacious method for treating cancer. Herein, we describe
      synthetic studies of imidazo[1,2-b]pyridazine derivatives as VEGF receptor 2
      (VEGFR2) kinase inhibitors. The imidazo[1,2-b]pyridazine scaffold was designed
      and synthesized as a hinge binder according to the previously reported crystal
      structure of pyrrolo[3,2-d]pyrimidine 1 with VEGFR2. Structure-activity
      relationship studies revealed that meta-substituted 6-phenoxy-imidazo[1,2
      b]pyridazine derivatives had potent affinity for VEGFR2. In particular, N-[3
      (imidazo[1,2-b]pyridazin-6-yloxy)phenyl]-3-(trifluoromethyl)benzamide (6b)
      exhibited strong inhibitory activity against VEGFR2 with an IC(50) value of 7.1
      nM, and it inhibited platelet-derived growth factor receptor beta kinase with an
      IC(50) value of 15 nM.

PMID- 23123017
TI  - Synthesis and docking studies of novel antitumor benzimidazoles.
AB  - In this work, the benzimidazole-pyrrole conjugates 6a-h and benzimidazole
      tetracycles conjugates 12-14 were prepared. The cytotoxicity of the compounds 3,
      4a-h, 6a-h, 8, 10 and 12-14 was tested against lung cancer cell line A549.
      Compound 6b exhibited higher activity than the bis-benzoxazole natural product
      (UK-1), the standard. The tested 4g,h, 6a-h, 10 and 12-14 exhibited remarkable
      cytotoxicity activity against breast cancer cell line MCF-7 with higher activity
      than tamoxifen. Furthermore, compound 4h was found to be also more potent than
      doxurubicin. The antitumor promotion activity of synthesized compounds 4g,h, 6a
      h, 10 and 12-14 has been estimated by studying their possible inhibitory effects
      on EBV-EA activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Among
      the studied compounds, the inhibitory activities of compounds 8, 13 and 14
      demonstrated strong inhibitory effects on the Epstein-Barr virus early antigen
      (EBV-EA) activation without showing any cytotoxicity on the Raji cells and their
      effects being stronger than that of a representative control, oleanolic acid.
      Moreover, the molecular docking of the new compounds into plasminogen activator
      (uPA) receptor has been in correlation with the antitumor activity. All
      synthesized compounds 3, 4a-h, 6a-h, 8, 10 and 12-14 were docked into same groove
      of the binding site of the native co-crystalized (4-iodobenzo[b]thiophene-2
      carboxamidine) ligand (PDB code:1c5x) for activity explaination. Compounds 4h, 6b
      and 13, giving the best docking results, were further studied to estimate their
      effect on the level of uPA using AssayMax human urokinase (uPA) ELISA kit. In
      case of A549 cell line, compound 6 exhibited similar activity to MMC, and for MCF
      7 cell line, compound 4h exhibited similar activity to doxorubicin, in inhibiting
      the expression of uPA.

PMID- 23123018
TI  - PER.C6((r)) cells as a serum-free suspension cell platform for the production of
      high titer poliovirus: a potential low cost of goods option for world supply of
      inactivated poliovirus vaccine.
AB  - There are two highly efficacious poliovirus vaccines: Sabin's live-attenuated
      oral polio vaccine (OPV) and Salk's inactivated polio vaccine (IPV). OPV can be
      made at low costs per dose and is easily administrated. However, the major
      drawback is the frequent reversion of the OPV vaccine strains to virulent
      poliovirus strains which can result in Vaccine Associated Paralytic Poliomyelitis
      (VAPP) in vaccinees. Furthermore, some OPV revertants with high transmissibility
      can circulate in the population as circulating Vaccine Derived Polioviruses
      (cVDPVs). IPV does not convey VAPP and cVDPVs but the high costs per dose and
      insufficient supply have rendered IPV an unfavorable option for low and middle
      income countries. Here, we explored whether the human PER.C6((r)) cell-line,
      which has the unique capability to grow at high density in suspension, under
      serum-free conditions, could be used as a platform for high yield production of
      poliovirus. PER.C6((r)) cells supported replication of all three poliovirus
      serotypes with virus titers ranging from 9.4 log(10) to 11.1 log(10)TCID(50)/ml
      irrespective of the volume scale (10 ml in shaker flasks to 2 L in bioreactors).
      This production yield was 10-30 fold higher than in Vero cell cultures performed
      here, and even 100-fold higher than what has been reported for Vero cell cultures
      in literature [38]. In agreement, the D-antigen content per volume PER.C6((r))
      derived poliovirus was on average 30-fold higher than Vero-derived poliovirus.
      Interestingly, PER.C6((r)) cells produced on average 2.5-fold more D-antigen
      units per cell than Vero cells. Based on our findings, we are exploring
      PER.C6((r)) as an interesting platform for large-scale production of poliovirus
      at low costs, potentially providing the basis for global supply of an affordable
      IPV.

PMID- 23123019
TI  - Theory-based predictors of influenza vaccination among pregnant women.
AB  - BACKGROUND: Guidelines recommend influenza vaccination for pregnant women, but
      vaccine uptake in this population is far below the goal set by Healthy People
      2020. The purpose of this study was to examine predictors of seasonal influenza
      vaccination among pregnant women. METHODS: Between 2009 and 2012, the Vaccines
      and Medications in Pregnancy Surveillance System (VAMPSS) conducted a prospective
      cohort study of influenza vaccine safety among pregnant women in the US and
      Canada that oversampled vaccinated women. Data for the present paper are from an
      additional cross-sectional telephone survey completed during the 2010-2011
      influenza season. We examined predictors of influenza vaccination, focusing on
      Health Belief Model (HBM) constructs. RESULTS: We surveyed 199 pregnant women,
      81% of whom had received a seasonal influenza vaccine. Vaccination was more
      common among women who felt more susceptible to influenza (OR=1.82, 95% CI 1.10
      3.01), who perceived greater vaccine effectiveness (OR=3.92, 95% CI 1.48-10.43),
      and whose doctors recommended they have flu shots (OR=3.06, 95% CI 1.27-7.38).
      Those who perceived greater barriers of influenza vaccination had lower odds of
      vaccination (OR=0.19, 95% CI 0.05-0.75). Perceived social norms, anticipated
      inaction regret, and worry also predicted uptake, though demographic
      characteristics of respondents did not. CONCLUSION: The HBM provides a valuable
      framework for exploring influenza vaccination among pregnant women. Our results
      suggest several potential areas of intervention to improve vaccination rates.

PMID- 23123020
TI  - Pandemic unadjuvanted influenza A (H1N1) vaccine in dermatomyositis and
      polymyositis: immunogenicity independent of therapy and no harmful effect in
      disease.
AB  - The goal of the present study was to evaluate the influence of the influenza A
      H1N1/2009 vaccine on dermatomyositis/polymyositis (DM/PM) disease parameters and
      the potential deleterious effect of therapy on immune response. Thirty-seven DM
      and 21 PM patients (Bohan and Peter's criteria) were gender- and age-matched to
      116 healthy controls. Seroprotection, seroconversion, the geometric mean titers
      (GMTs) and the factor increase (FI) in the GMTs were calculated. Disease safety
      was determined from a muscle enzyme analysis and the DM/PM scores [patient's
      visual analog scale (VAS), physician's VAS, manual muscle strength (MMT-8)]
      evaluated pre- and post-vaccination. The mean age (43.1+/-9.9 vs. 43.8+/-8.4
      years, p=0.607) and gender distribution (p=1.00) were comparable between the
      patients and controls. After 21 days, seroconversion (p=0.394), seroprotection
      (p=0.08), GMT (p=0.573) and the FI in the GMT (p=0.496) were similar in both
      groups. The disease and muscle parameters remained stable throughout the study,
      including the creatine kinase (p=0.20) and aldolase levels (p=0.98), the
      physicians' VAS (p=1.00), the patients' VAS (p=1.00) and the MMT-8 (p=1.00).
      Regarding the influence of treatment, the seroconversion rates were comparable
      between the controls and patients undergoing treatment with glucocorticoid (GC)
      (p=0.969), GC >0.5mg/kg/day (p=0.395) and GC+immunosuppressors (p=0.285). Vaccine
      related adverse events were mild and similar in the DM/PM and control groups
      (p>0.05). Our data support the administration of the pandemic influenza A
      H1N1/2009 vaccination in DM/PM, as we found no short-term harmful effects related
      to the disease itself and adequate immunogenicity in spite of therapy. Further
      studies are necessary to identify any long-term adverse effects in patients with
      these diseases.

PMID- 23123022
TI  - Vaccine-related standard of care and willingness to respond to public health
      emergencies: a cross-sectional survey of California vaccine providers.
AB  - INTRODUCTION: Responding to a vaccine-related public health emergency involves a
      broad spectrum of provider types, some of whom may not routinely administer
      vaccines including obstetricians, pharmacists and other specialists. These
      providers may have less experience administering vaccines and thus less
      confidence or self-efficacy in doing so. Self-efficacy is known to have a
      significant impact on provider willingness to respond in emergency situations.
      METHODS: We conducted a survey of 800 California vaccine providers to investigate
      standard of care, willingness to respond, and how vaccine-related standard of
      care impacts willingness to respond among these providers. We used linear
      regression to examine how willingness to respond was impacted by vaccine-related
      standard of care. RESULTS: Forty percent of respondents indicated that they had
      participated in emergency preparedness training, actual disaster response, or
      surge capacity initiatives with significant differences among provider types for
      all measures (p=0.007). When asked to identify barriers to responding to a public
      health emergency, respondents indicated that staff size or capacity, training and
      resources were the top concerns. Respondents in practices with a higher vaccine
      related standard of care had a higher willing to respond index (beta=0.190,
      p=0.001). Respondents who had participated in emergency training or actual
      emergency response had a higher willing to respond index (beta=1.323, p<0.0001).
      CONCLUSION: Our study suggests that concerns about staff size and surge capacity
      need to be more explicitly addressed in current emergency preparedness training
      efforts. In the context of boosting response willingness, larger practice
      environments stand to benefit from self-efficacy focused training and exercise
      efforts that also incorporate standard of care.

PMID- 23123021
TI  - High immunogenicity of nicotine vaccines obtained by intradermal delivery with
      safe adjuvants.
AB  - Immunotherapy for tobacco addiction may offer a safe, alternative treatment if
      the immunogenicity of the current nicotine vaccines can be improved. We show here
      that intradermal (ID) immunization induces the production of antibody directed
      against nicotine (NicAb) at a much higher level than conventional intramuscular
      (IM) immunization. The magnitude and duration of NicAb production was further
      increased robustly by non-inflammatory laser vaccine adjuvant (LVA), slightly
      inflammatory monophosphoryl lipid A (MPL) or a combination of MPL and CpG
      adjuvants. Consequently, significantly fewer vaccination doses were required to
      attain a high level of NicAb production for an extended period of time and reduce
      nicotine entry into the brain in the presence of LVA, MPL or MPL/CpG adjuvant,
      respectively. Yet, the potency of these adjuvants to augment ID nicotine vaccine
      immunogenicity came at the expense of local skin reactogenicity, with LVA causing
      little skin reaction and MPL/CpG stimulating overt skin irritation. These
      observations underscore a necessity of a balance between optimal adjuvant potency
      and undesired local reactogenicity. In summary, our study presents a novel
      approach to significantly improve nicotine vaccine immunogenicity by a
      combination of safe cutaneous vaccine adjuvants with ID immunization.

PMID- 23123023
TI  - Functional impacts of the diversity of the meningococcal factor H binding
      protein.
AB  - Neisseria meningitidis is a human pathogenic bacterium responsible for life
      threatening and rapidly evolving invasive infections. Several bacterial virulence
      factors may play primordial roles during host-bacteria interactions. The
      meningococcal factor H binding protein, fHbp, interacts with the complement
      negative regulator, factor H (fH), to enhance meningococcal survival. fHbp is a
      major component in recombinant vaccines against meningococci that are under
      development. In 2010, we detected variations in fhbp gene during an outbreak
      provoked by serogroup C isolates belonging to the clonal complex, ST-11. We
      therefore explored 680 meningococcal isolates (88% of all invasive isolates in
      2009 and 2010) by DNA sequencing of fhbp gene. The level of fHbp at the bacterial
      surface was determined by ELISA and flow cytometry using anti-fHbp antibodies. We
      also analyzed the interaction of fHbp with human fH as well as the deposition of
      C3b complement component. We observed important sequence diversity of fHbp in
      particular within regions known to interact with fH. The distribution of fhbp
      alleles differed among meningococcal serogroups and clonal complexes. This
      diversity affected directly binding of fH to fHbp and seemed to influence the
      deposition of the complement C3b component on the bacterial surface. However,
      bacterial killing by anti-fHbp antibodies was still achieved and required a
      minimum level of fHbp at the bacterial surface regardless the binding to fH or
      sequence diversity. These data have impacts on our understanding of the role of
      fHbp in meningococcal pathogenesis. They also provide data on the diversity of
      fhbp before the introduction of vaccines targeting fHbp and stress the need to
      include characterization of fHbp in typing schemes of meningococcal isolates.

PMID- 23123024
TI  - Kinetic and HPV infection effects on cross-type neutralizing antibody and avidity
      responses induced by Cervarix((r)).
AB  - BACKGROUND: We previously demonstrated that Cervarix((r)) elicits antibody
      responses against vaccine-related types for which clinical efficacy was
      demonstrated (HPV-31 and -45). Here, we evaluated the kinetics of neutralization
      titers and avidity of Cervarix((r))-induced antibodies up to 36 months of follow
      up in unexposed and HPV infected women. METHODS: A subset of women who
      participated in the Cost Rica HPV-16/18 Vaccine Trial had pre- and post
      vaccination sera tested for antibody responses to HPV-16, -18, -31, -45, and -58
      using a pseudovirion-based neutralization assay, and HPV-16 antibody avidity
      using an HPV-16 L1 VLP (virus-like particle)-based ELISA developed in our
      laboratory. RESULTS: In uninfected women, neutralizing antibody titers did not
      reach significance until after the 3rd dose for HPV-31 (month 12, p=0.009) and
      HPV-45 (month 12, p=0.003), but then persisted up to month 36 (HPV-31, p=0.01;
      HPV-45, p=0.002). Individuals infected with HPV-16 or HPV-31 at enrollment
      developed a significantly higher median antibody response to the corresponding
      HPV type after one dose, but there was not a difference between median titers
      after three doses compared to the HPV negative group. Median HPV-16 antibody
      avidity and titer increased over time up to month 12; however, the HPV-16 avidity
      did not correlate well with HPV-16 neutralizing antibody titers at each time
      point examined, except for month 6. The median avidity levels were higher in HPV
      16 infected women at month 1 (p=0.04) and lower in HPV-16 infected women at month
      12 (p=0.006) compared to the HPV negative women. CONCLUSIONS: The persistence of
      cross-neutralization titers at month 36 suggests cross-reactive antibody
      responses are likely to persist long-term and are not influenced by infection
      status at enrollment. However, the weak correlation between avidity and
      neutralization titers emphasizes the need for examining avidity in efficacy
      studies to determine if high avidity antibodies play a critical role in
      protection against infection.

PMID- 23123025
TI  - Controlling pore size and uniformity of mesoporous titania by early stage low
      temperature stabilization.
AB  - The control of the formation process during and after self-assembly is of utmost
      importance to achieve well structured, controlled template-assisted mesoporous
      titania materials with the desired properties for various applications via the
      evaporation induced self-assembly method (EISA). The present paper reports on the
      large influence of the thermal stabilization and successive template removal on
      the pore structure of a mesostructured TiO(2) material using the diblock
      copolymer Brij 58 as surfactant. A controlled thermal stabilization (temperature
      and duration) allows one to tailor the final pore size and uniformity much more
      precise by influencing the self-assembly of the template. Moreover, also the
      successive thermal template removal needs to be controlled in order to avoid a
      structural collapse. N(2)-sorption, TGA, TEM, FT-Raman spectroscopy, and small
      angle & wide angle XRD have been used to follow the crystal growth and
      mesostructure organization after thermal stabilization and after thermal template
      removal, revealing its effect on the final pore structure.

PMID- 23123026
TI  - Silylation of montmorillonite surfaces: dependence on solvent nature.
AB  - Silylation of clay mineral surfaces has attracted much attention due to their
      extensive applications in materials science and environmental engineering.
      Silylation of montmorillonite surfaces with 3-aminopropyltriethoxysilane was
      carried out in polar-protic and nonpolar solvents. The swelling property of the
      silylated montmorillonites was investigated by intercalating with
      cetyltrimethylammonium bromide. Silylated montmorillonites prepared in nonpolar
      solvents showed a larger amount of loaded silane and a higher extent of
      condensation among different silane molecules, comparing with those prepared in
      polar-protic solvents with high dielectric constant. Meanwhile, the silylated
      montmorillonites prepared in nonpolar solvents displayed poor swelling property
      due to the linkage between silane oligomers and clay layers, that is, the
      neighboring clay layers were locked by the silane oligomers. The present study
      demonstrated that the polarity of the solvents used had an important influence on
      the extent of grafting, interlayer structure, and swelling property of the
      silylated products. This is of high importance for synthesis and application of
      silylated clay minerals.

PMID- 23123027
TI  - Use of polyelectrolyte complexes and multilayers from polymers and nanoparticles
      to create sacrificial bonds between surfaces.
AB  - In this study, particle polyelectrolyte complexes (PPECs) were formed by mixing
      cationic polyacrylamide (CPAM) and silica nanoparticles using the jet mixing
      technique. Within certain limits, the size of the formed PPECs could be
      controlled. The aim was to prepare PPECs with embedded sacrificial bonds, similar
      to those found in bones. Examination of PPEC adsorption to silica model surfaces
      indicated that smaller PPECs adsorbed to a higher level than larger ones, due to
      the higher diffusion speed of smaller complexes. Adsorption studies of the same
      components as in the PPECs, but arranged in multilayers, that is, particle
      polyelectrolyte multilayers (PPEMs), indicated a stable, gradual build-up of
      material on the surface with smaller nanoparticles, whereas PPEMs comprising
      elongated nanoparticles appeared to be more loosely adsorbed onto the surface
      when the nanoparticles were in the outer layer, due to repulsive forces within
      the adsorbed layer. The AFM colloidal probe technique was used to study the
      interaction between surfaces treated with PPECs, multilayers, or polyelectrolyte
      complexes (PECs). The results showed that the expected long-range disentanglement
      could be achieved with PPECs but that the pull-off forces were generally low.
      Treatment with PPEMs comprising the same polymer and nanoparticle components
      produced higher pull-off values, together with disentanglement behaviour,
      possibly due to better contact between the surfaces. Adhesion experiments with
      polymer PECs showed significantly higher pull-off values than with the PPECs,
      probably due to polymer interdiffusion across the surface boundary.

PMID- 23123028
TI  - Effect of sodium on photovoltaic properties of dye-sensitized solar cells
      assembled with anatase TiO2 nanosheets with exposed {001} facets.
AB  - Anatase TiO(2) nanosheets with exposed reactive {001} facets were prepared in the
      presence of HF. The photovoltaic properties of NaOH-washed anatase TiO(2)
      nanosheets with exposed {001} facets were investigated by assembling the TiO(2)
      as photoanodes in dye-sensitized solar cells (DSSCs). A decreased overall
      efficiency and increased recombination rate was observed in comparison with the
      H(2)O-washed counterpart by both dark current scan and open-circuit voltage decay
      scan, and XPS confirmed that the deleterious effect of sodium ions is responsible
      for this reduced efficiency in DSSCs.

PMID- 23123029
TI  - Control over the color transition behavior of polydiacetylene vesicles using
      different alcohols.
AB  - In this contribution, we investigate the color transition behavior of
      polydiacetylene (PDA) vesicles upon exposure to different chemical stimuli. A
      series of linear and branched alcohols are used as model additives, allowing
      systematic control of their molecular shape and polarity. The PDA vesicles are
      fabricated by using three monomers, 10,12-pentacosadiynoic acid (PCDA), 10,12
      tricosadyinoic acid (TCDA), and N-(2-amino ethyl)pentacosa-10,12-dyinamide
      (AEPCDA). When a series of linear alcohols is used, the longer alcohol length
      causes color transition of all PDA vesicles. In this system, the penetration of
      linear alcohols into the inner layer of PDA vesicles is dictated by their
      polarity. The change of -OH position within the alcohol molecule also affects the
      degree of penetration. It requires a higher amount of the 2-propanol to induce
      color transitions of the PDAs compared to that of the 1-propanol. The addition of
      methyl branches into the hydrophobic tail of alcohols causes an increase in
      steric effect, which hinders the penetration as well. When the 2,2-dimethyl-1
      propanol is used as a stimulus, the color transition of PDAs occurs at much
      higher alcohol concentration compared to 2-methyl-1-butanol, 3-methyl-1-butanol,
      and 1-pentanol. The variation of PDA structures also affects their ability to
      interact with the alcohols. The modified head group of poly(AEPCDA) promotes the
      ability to distinguish between 1-propanol and 2-propanol or 1-propanol and
      ethanol.

PMID- 23123030
TI  - Synthesis and monolayer behavior of organogermanium clusters.
AB  - Several organogermanium clusters (Or-GeCs) with different organic capping
      reagents have been synthesized, and their monolayer behaviors on a water surface
      studied. GeCl(4) and organic bromides were reacted in a one-pot process using
      magnesium to synthesize the corresponding Or-GeCs. The structures of the Or-GeCs
      were characterized by UV-vis, NMR, and FT-IR spectroscopy. GPC measurements were
      also collected, and the results revealed that the cores of the clusters were
      composed of a 3-D Ge-Ge network capped with organic reagents. Surface pressure
      (pi)-area (A) isotherms and Brewster angle microscopy (BAM) measurements
      indicated that the Or-GeCs with alkyl capping regents formed an oil, whereas
      those with aromatic capping regents formed a solid-like monolayer at the air
      water interface. It was concluded that the occurrence of a pi-pi interaction
      between the aromatic capping reagents was necessary for the formation of a solid
      like film. Phenyl-GeCs, which contained a phenyl group capping reagent, were
      transferred onto a solid substrate using the Langmuir-Schaeffer method, and
      atomic force microscopy (AFM) images revealed a uniform film (root mean square
      roughness of 0.6 nm) of 3-4 nm in thickness. Furthermore, a multilayer phenyl-GeC
      film was prepared by repeating the deposition process.

PMID- 23123031
TI  - Hydroxide nanoparticles for cultural heritage: consolidation and protection of
      wall paintings and carbonate materials.
AB  - Colloids and Material Science are nowadays providing innovative and effective
      technological solutions in a wide range of applicative fields. In the last
      decade, nanomaterials have been specifically designed to ensure the long-term
      restoration and preservation of movable and immovable artworks. The main tasks to
      address by conservation scientists concern the cleaning, the deacidification and
      the consolidation of different kinds of artistic substrates. The aim of the
      present contribution is to provide an up-to-date overview on the synthesis and
      preparation of colloidal systems tailored to the consolidation and protection of
      wall paintings, plasters and stones, highlighting the most recent improvements.
      Two case studies, widely representative of typical consolidation problems, are
      presented, i.e. the preservation of wall paintings belonging to a Mesoamerican
      archeological site and the consolidation of two Italian Renaissance buildings.

PMID- 23123032
TI  - Drying patterns of porous media containing wettability contrasts.
AB  - Porous media containing sharp wettability discontinuities may occur in natural
      systems due to depositional processes, accumulation of organic layers or
      modification of soil wettability following intense forest fires all of which are
      known to significantly modify water flow and transport processes. We studied
      evaporation from sand columns containing hydraulically-interacting domains with
      sharp wettability contrasts. We employed neutron transmission technique to map
      liquid phase dynamics during evaporation, and conducted laboratory experiments to
      evaluate evaporative fluxes affected by interactions across wettability contrast.
      We explained the preferential drying front displacement in the hydrophobic domain
      and the spatial extent of capillary flow supporting the vaporization plane using
      a physically-based model. The model provides description of observed liquid phase
      patterns and dynamics observed in neutron radiography measurements and
      evaporative fluxes from laboratory experiments. Our results provide new insights
      into evaporation induced capillary exchange and preferential liquid phase
      distribution during evaporation from hydraulically interacting vertical porous
      domains with differing wettability properties and offer opportunities for design
      of selectively drying of porous media in natural and engineered systems.

PMID- 23123033
TI  - Synthesis, characterization, and morphology study of poly(acrylamide-co-acrylic
      acid)-grafted-poly(styrene-co-methyl methacrylate) "raspberry"-shape like
      structure microgels by pre-emulsified semi-batch emulsion polymerization.
AB  - A novel microgels were polymerized using styrene (St), methyl methacrylate (MMA),
      acrylamide (AAm), and acrylic acid (AAc) monomers in the presence of N,N'
      methylenebisacrylamide (MBA) cross-linker. Pre-emulsified monomer was first
      prepared followed by polymerizing monomers using semi-batch emulsion
      polymerization. Fourier Transform Infrared Spectroscopy (FTIR) and (1)H Nuclear
      Magnetic Resonance (NMR) were used to determine the chemical structure and to
      indentify the related functional group. Grafting and cross-linking of
      poly(acrylamide-co-acrilic acid)-grafted-poly(styrene-co-methyl methacrylate)
      [poly(AAm-co-AAc)-g-poly(St-co-MMA)] microgels are approved by the disappearance
      of band at 1300 cm(-1), 1200 cm(-1) and 1163 cm(-1) of FTIR spectrum and the
      appearance of CH peaks at 5.5-5.7 ppm in (1)H NMR spectrum. Scanning Electron
      Microscope (SEM) images indicated that poly(St-co-MMA) particle was lobed
      morphology coated by cross-linked poly(AAm-co-AAc) shell. Furthermore, SEM
      results revealed that poly(AAm-co-AAc)-g-poly(St-co-MMA) is composite particle
      that consist of "raspberry"-shape like structure core. Internal structures of the
      microgels showed homogeneous network of pores, an extensive interconnection among
      pores, thicker pore walls, and open network structures. Water absorbency test
      indicated that the sample with particle size 0.43 MUm had lower equilibrium water
      content, % than the sample with particle size 7.39 MUm.

PMID- 23123034
TI  - Nurses' decision-making process in cases of physical restraint in acute elderly
      care: a qualitative study.
AB  - BACKGROUND: The increasing vulnerability of patients in acute elderly care
      requires constant critical reflection in ethically charged situations such as
      when employing physical restraint. Qualitative evidence concerning nurses'
      decision making in cases of physical restraint is limited and fragmented. A
      thorough understanding of nurses' decision-making process could be useful to
      understand how nurses reason and make decisions in ethically laden situations.
      OBJECTIVES: The aims of this study were to explore and describe nurses' decision
      making process in cases of physical restraint. DESIGN: We used a qualitative
      interview design inspired by the Grounded Theory approach. Data analysis was
      guided by the Qualitative Analysis Guide of Leuven. SETTING: Twelve hospitals
      geographically spread throughout the five provinces of Flanders, Belgium.
      PARTICIPANTS: Twenty-one acute geriatric nurses interviewed between October 2009
      and April 2011 were purposively and theoretically selected, with the aim of
      including nurses having a variety of characteristics and experiences concerning
      decisions on using physical restraint. RESULTS: In cases of physical restraint in
      acute elderly care, nurses' decision making was never experienced as a fixed
      decision but rather as a series of decisions. Decision making was mostly reasoned
      upon and based on rational arguments; however, decisions were also made routinely
      and intuitively. Some nurses felt very certain about their decisions, while
      others experienced feelings of uncertainty regarding their decisions.
      CONCLUSIONS: Nurses' decision making is an independent process that requires
      nurses to obtain a good picture of the patient, to be constantly observant, and
      to assess and reassess the patient's situation. Coming to thoughtful and
      individualized decisions requires major commitment and constant critical
      reflection.

PMID- 23123035
TI  - [Cost analysis of liver transplantation in a community hospital: association with
      the Model for End-stage Liver Disease, a prognostic index to prioritize the most
      severe patients].
AB  - INTRODUCTION: The aim of the present study was to investigate the impact of the
      Model for End-stage Liver Disease (MELD) on transplantation costs. MATERIAL AND
      METHODS: We included all patients who received a liver transplant for end-stage
      liver disease between 2006 and 2010. The study period encompassed the day of
      transplantation until hospital discharge. The patients were classified into two
      groups: those with a MELD score of 6-19 and those with a score of 20-40. RESULTS:
      The mean MELD score at transplantation was 19.2+/-7.0 (mean+/-SD). The mean cost
      per procedure in the study period was USD 33,461 per patient (range 21,795
      104,629). The cost of transplantation was USD 30,493+/-8,825 in patients with a
      MELD score of 6-19 and was USD 36,506+/-15,833 in those with a score of 20-40;
      this difference was statistically significant (P=.04). In a stepwise logistic
      regression analysis, the only independent predictor of high cost was having a
      MELD score of 20 (OR 11.8; CI 1.6-87). In the linear regression model, the most
      important predictor of cost was the length of hospital stay (r(2)=43%).
      DISCUSSION: Our results demonstrate that the MELD score directly affects
      transplantation costs. We suggest that reimbursement systems compensate the
      distinct financing bodies according to the severity of the underlying disease,
      evaluated with the MELD.

PMID- 23123036
TI  - Insulin-regulated aminopeptidase and its compartment in dendritic cells.
AB  - Peptide epitopes presented by MHC class I molecules are produced through
      sequential proteolysis, frequently terminating with an aminoterminal trimming
      step. While the trimming enzymes processing endogenous MHC class I ligands in the
      endoplasmic reticulum have by now been characterized extensively, we have only
      recently identified an endosomal enzyme, insulin-regulated aminopeptidase (IRAP)
      that can trim cross-presented peptides derived from proteins internalized by
      dendritic cells. Here we summarize the essential features of IRAP as a trimming
      enzyme, propose an updated model of cellular cross-presentation pathways, and
      discuss potential additional functions of IRAP and its compartment in dendritic
      cell biology.

PMID- 23123037
TI  - Unsuccessful regeneration of the semitendinosus tendon harvested for anterior
      cruciate ligament reconstruction: report of two cases.
AB  - Recent magnetic resonance imaging (MRI) and three-dimensional (3D) computed
      tomography (CT) analyses have demonstrated that semitendinosus tendon can
      regenerate at a high rate following harvesting the tendon for anterior cruciate
      ligament (ACL) reconstruction. Although it is known that the regeneration of the
      semitendinosus tendon does not occur in all the patients, the reason for this
      unsuccessful regeneration of the tendon in certain patients remains unknown. We
      recently encountered two cases in which regeneration of the semitendinosus tendon
      was unsuccessful because of apparent reasons. These patients experienced a sudden
      sharp pain in the posterior aspect of their thighs when their hamstring muscles
      were subjected to aggressive load at 3 and 4 weeks after surgery. At the follow
      up examination conducted after 12 months, 3D CT imaging revealed unsuccessful
      regeneration of the semitendinosus tendons in both cases. Severe proximal
      retraction of the semitendinosus muscle belly was also confirmed.

PMID- 23123039
TI  - Continuous infusion of bupivacaine following total knee arthroplasty: a
      randomized control trial pilot study.
AB  - An RCT pilot-study was conducted to assess efficacy of a 48-h continuous local
      infiltration of intra-articular bupivacaine (0.5% at 2 cc/h) versus placebo (0.5%
      saline at 2 cc/h) in decreasing PCA morphine consumption following TKA. Secondary
      outcomes included 48-h VAS pain, opioid side effects, length of stay, and knee
      function scores up to 1-year postoperatively. Of 67 randomized patients, 49
      completed the trial including 24 bupivacaine, and 25 placebo patients. Mean 48-h
      PCA morphine consumption did not differ significantly between treatment (39 mg +/
      27.1) and placebo groups (53 mg +/- 30.4) (P = .137). The intervention did not
      improve pain scores, or any other outcome studied. Given study results we would
      conclude that analgesia outcomes with a multimodal analgesia regimen are not
      significantly improved by adding 48 h of 0.5% bupivacaine infiltration at 2 cc/h.

PMID- 23123040
TI  - Do ion concentrations after metal-on-metal hip resurfacing increase over time? A
      prospective study.
AB  - Thirteen male and five female patients received a Conserve Plus hip resurfacing
      and prospectively provided blood samples to measure cobalt and chromium levels
      for up to 11 years. Trends in metal levels over time in unilateral and bilateral
      patients were studied. A multi-variate regression model was used to account for
      potential covariates. For unilaterals over all time intervals, the median Serum
      Cobalt level (CoS) was 1.06 MUg/L, while the median Serum Chromium level (CrS)
      was 1.58 MUg/L. For bilaterals, the median post operative CoS was 2.80 MUg/L,
      while the median CrS was 5.80 MUg/L. Metal levels increased within the first year
      then decreased and stabilized. These results show that serum metal levels in well
      functioning implants can be low and do not increase with time.

PMID- 23123038
TI  - Molecular identification, cloning and characterization of transmitted/founder HIV
      1 subtype A, D and A/D infectious molecular clones.
AB  - We report the molecular identification, cloning and initial biological
      characterization of 12 full-length HIV-1 subtype A, D and A/D recombinant
      transmitted/founder (T/F) genomes. T/F genomes contained intact canonical open
      reading frames and all T/F viruses were replication competent in primary human T
      cells, although subtype D virus replication was more efficient (p<0.05). All 12
      viruses utilized CCR5 but not CXCR4 as a co-receptor for entry and exhibited a
      neutralization profile typical of tier 2 primary virus strains, with significant
      differences observed between subtype A and D viruses with respect to sensitivity
      to monoclonal antibodies VRC01, PG9 and PG16 and polyclonal subtype C anti-HIV
      IgG (p<0.05 for each). The present report doubles the number of T/F HIV-1 clones
      available for pathogenesis and vaccine research and extends their representation
      to include subtypes A, B, C and D.

PMID- 23123041
TI  - Computed tomography morphometric study of gender differences in osteoarthritis
      proximal tibias.
AB  - One hundred and thirty osteoarthritic knees(65 males, 65 females) from a Chinese
      population were measured by computed tomography for tibial mediolateral (ML),
      middle anteroposterior (AP), medial anteroposterior (MAP), lateral
      anteroposterior (LAP) dimensions and ML/AP aspect ratio. The ML/AP aspect ratio
      were classified into 3 groups based on AP dimensions(<48 mm, 48-52 mm, >52 mm) to
      compare the morphologic differences of proximal tibia between males and females.
      The mean ML, AP, MAP and LAP dimensions of proximal tibia showed significant
      differences for sex (P < .01). We found a progressively decreased in the ML/AP
      aspect ratio with an increasing AP dimension, and males have larger ML/AP aspect
      ratio than that of females under a given AP dimension (P < .01). This indicates
      that under a given AP dimension prosthesis, the tibial ML dimension have the
      potential to be undersized in males and to overhang in females. This study may
      provide important reference in designing proper gender-specific tibia prosthesis
      with different ML/AP aspect ratio for Chinese males and females. 

PMID- 23123042
TI  - Cementless metaphyseal sleeves used for large tibial defects in revision total
      knee arthroplasty.
AB  - Revision arthroplasty of large tibial defects remains a challenge. Thirty
      revision knee arthroplasties using a porous titanium tibial sleeve for Anderson
      Orthopaedic Research Institute (AORI) Type 2B and Type 3 defects with minimum
      2year follow up were retrospectively reviewed. The average Knee Society Score
      increased from 55 pre-operatively to 92 post-operatively. Six patients had a
      repeat operation though none were sleeve related. All radiographs at final follow
      up showed well fixed components with osseous in-growth. Seven patients had end-of
      stem pain, four of which resolved. Our short-term results show that porous
      titanium sleeves are a promising option when managing large areas of metaphyseal
      bone loss by filling defects and providing stable construct with biologic
      fixation.

PMID- 23123043
TI  - Rapid EPA and DHA incorporation and reduced PGE2 levels after one week
      intervention with a medical food in cancer patients receiving radiotherapy, a
      randomized trial.
AB  - BACKGROUND & AIMS: In cancer patients, metabolic alterations, reduced immune
      competence and anti-cancer treatment can increase the risk of infections. A rapid
      acting nutritional intervention might reduce this risk and support overall
      treatment. The present study investigated whether one week of intervention with a
      specific medical food led to fatty acid incorporation and functional
      immunological changes. METHODS: In a randomized, double-blind study, 38 cancer
      patients receiving radiotherapy consumed daily for one week 400 ml of specific
      medical food, which is high in protein and leucine, and enriched with fish oil
      and specific oligosaccharides (Active group), or iso-caloric/iso-nitrogenous
      product (Control group). Blood samples were taken at day 0 (baseline) and day 7.
      RESULTS: After one week of intervention, the incorporation of EPA and DHA in
      white blood cells was significantly higher in the Active group (2.6% and 2.6% of
      total fatty acids) compared to the Control group (1.0% and 2.2% of total fatty
      acids) (p < 0.001 and p < 0.05). Serum PGE2 levels decreased in the Active group
      and increased in the Control group (p < 0.01). No differences were observed on
      cytokine production in LPS-stimulated whole blood cultures. CONCLUSIONS: In
      cancer patients receiving radiotherapy, nutritional intervention with a specific
      medical food rapidly increased the percentage EPA and DHA in white blood cell
      phospholipids and reduced serum levels of the inflammatory mediator PGE2 within
      one week. CLINICAL REGISTRATION NUMBER: NTR2121.

PMID- 23123044
TI  - Borderline symptoms and suicidality/self-injury in late adolescence:
      prospectively observed relationship correlates in infancy and childhood.
AB  - The primary objective was to assess whether prospectively observed quality of
      parent-child interaction in infancy and middle childhood contributed to the
      prediction of borderline symptoms and recurrent suicidality/self-injury in late
      adolescence. Adolescents (mean 19.9 years) from 56 families participating in a
      longitudinal study since infancy (retention rate 74%) were assessed on the SCID
      II for symptoms of borderline personality disorder (BPD), including
      suicidality/self-injury. Early clinical risk was indexed by clinical referral to
      parent-infant services. Attachment security and parent-child interaction were
      assessed from videotape at 18 months and 8 years. Severity of childhood abuse was
      rated from interview and self-report measures. Maternal withdrawal in infancy was
      a significant predictor of both borderline symptoms and suicidality/self-injury
      in late adolescence. Disorganized controlling child behavior at age 8 contributed
      independently to the prediction of borderline symptoms. The effect of maternal
      withdrawal was independent of, and additive to, variability explained by severity
      of childhood abuse. Borderline symptoms and suicidality/self-injury may be
      preceded developmentally by disturbed interactions as early as 18 months of age.
      A parent-child transactional model is proposed to account for the findings.

PMID- 23123046
TI  - Psychological predictors of the recovery from mood or anxiety disorder in short
      term and long-term psychotherapy during a 3-year follow-up.
AB  - Choice of optimal treatment length for psychiatric patients requires knowledge
      about the patients' pre-treatment suitability. This study compares the prediction
      of seven psychological suitability measures on changes in psychiatric symptoms in
      short- and long-term psychotherapy over a 3-year follow-up. The psychological
      suitability of 326 outpatients from the Helsinki Psychotherapy Study, aged 20-46
      years, and suffering from mood or anxiety disorders, was assessed at baseline
      using the Suitability for Psychotherapy Scale (SPS) before randomly assigning
      them to solution-focused therapy, short-term or long-term psychodynamic
      psychotherapy. Psychiatric symptoms (Symptom Checklist-90 Global Severity Index)
      were assessed at baseline and seven times during follow-up. Three patient groups
      with different prognosis were found when a cumulative SPS score, summing up the
      values of the seven single suitability measures, was used to predict symptom
      development: patients with more good (4 or more) than poor values benefited more
      from short-term therapy, patients with more poor (4-6) than good values benefited
      more from long-term therapy, and patients with all seven values poor failed to
      benefit from either short- or long-term therapy. The SPS can apparently be
      applied before the start of treatment to predict the amount of therapy patients
      need to recover, although its suitability in therapies of different types needs
      to be confirmed. 

PMID- 23123045
TI  - Neural basis of implicit memory for socio-emotional information in schizophrenia.
AB  - Individuals with schizophrenia are impaired in processing social signals such as
      facial expressions of emotion. Perceiving facial expressions is a complex process
      that depends on a distributed neural network of regions involved in affective,
      cognitive, and visual processing. We examined repetition priming, a non-conscious
      form of perceptual learning, to explore the visual-perceptual processes
      associated with perceiving facial expression in people with schizophrenia.
      Functional magnetic resonance imaging (fMRI) was also employed to probe the
      sensitivity of face-responsive regions in the ventral pathway to the repetition
      of stimuli. Subjects viewed blocks of novel and repeated faces displaying fear
      expressions and neutral expressions and identified each face as male or female.
      Gender decisions were faster for repeated encoding relative to initial encoding
      of faces, indicating significant priming for facial expressions. Priming was
      normal in schizophrenia patients, but, as expected, recognition memory for the
      expressions was impaired. Neuroimaging findings showed that priming-related
      activation for patients was reduced in the left fusiform gyrus, relative to
      controls, regardless of facial expression. The findings suggest that
      schizophrenia patients have altered neural sensitivity in regions of the ventral
      visual processing stream that underlie early perceptual learning of objects and
      faces.

PMID- 23123047
TI  - Temperature dependence of stream aeration coefficients and the effect of water
      turbulence: a critical review.
AB  - The gas transfer velocity (K(L)) and related gas transfer coefficient (k(2) =
      K(L)A/V, with A, area and V, volume) at the air-water interface are critical
      parameters in all gas flux studies such as green house gas emission, whole stream
      metabolism or industrial processes. So far, there is no theoretical model able to
      provide accurate estimation of gas transfer in streams. Hence, reaeration is
      often estimated with empirical equations. The gas transfer velocity need then to
      be corrected with a temperature coefficient theta = 1.0241. Yet several studies
      have long reported variation in theta with temperature and 'turbulence' of water
      (i.e. theta is not a constant). Here we re-investigate thoroughly a key
      theoretical model (Dobbins model) in detail after discovering important
      discrepancies. We then compare it with other theoretical models derived from a
      wide range of hydraulic behaviours (rigid to free continuous surface water, wave
      and waterfalls with bubbles). The results of the Dobbins model were found to
      hold, at least theoretically in the light of recent advances in hydraulics,
      although the more comprehensive results in this study highlighted a higher degree
      of complexity in theta's behaviour. According to the Dobbins model, the
      temperature coefficient theta, could vary from 1.005 to 1.042 within a
      temperature range of 0-35  degrees C and wide range of gas transfer velocities,
      i.e. 'turbulence' condition (0.005 < K(L) < 1.28 cm min(-1)). No other
      theoretical models showed any significant variability in theta with change in
      'turbulence', and only modest variability in theta with change in temperature.
      However, the other theoretical models did not have the same temperature
      coefficient theta (with 1.000 < theta < 1.056 within 0-35  degrees C). A model
      integrating turbulence and bubble mediated gas transfer velocities suggested a
      lower temperature dependence for bubble (1.013<theta < 1.017) than turbulence
      (1.023<theta < 1.031) mediated processes. As it stands, the effect of turbulence
      on the temperature dependence of gas transfer at the air-water interface has
      still to be clarified, although many models simulate different flow conditions
      which may explain some of the observed discrepancies. We suggest that the
      temperature dependence curves produced by the Dobbins model may be used
      tentatively as a simple theoretical guide for streams with free surface water but
      not self-aerated flows encountered in whitewater rapids, cascades or weirs.
      Greater awareness of the different models and conditions of applications should
      help choosing an appropriate correction. Three case studies investigated the
      effect of the temperature coefficient on reaeration and stream metabolism
      (photosynthesis and respiration). In practice, the temperature correction may be
      an important parameter under constant turbulence conditions, but as the range in
      turbulence increases, the role of temperature may become negligible in
      determining K(L), whatever the temperature correction. The theoretical models
      reviewed here are also useful references to correct K(L) values determined using
      a reference tracer gas to a second species of interest.

PMID- 23123048
TI  - Effect of platform, reference material, and quantification model on enumeration
      of Enterococcus by quantitative PCR methods.
AB  - Quantitative polymerase chain reaction (qPCR) is increasingly being used for the
      quantitative detection of fecal indicator bacteria in beach water. QPCR allows
      for same-day health warnings, and its application is being considered as an
      option for recreational water quality testing in the United States (USEPA, 2011.
      EPA-OW-2011-0466, FRL-9609-3, Notice of Availability of Draft Recreational Water
      Quality Criteria and Request for Scientific Views). However, transition of qPCR
      from a research tool to routine water quality testing requires information on how
      various method variations affect target enumeration. Here we compared qPCR
      performance and enumeration of enterococci in spiked and environmental water
      samples using three qPCR platforms (Applied Biosystem StepOnePlusTM, the BioRad
      iQTM5 and the Cepheid SmartCycler((r)) II), two reference materials (lyophilized
      cells and frozen cells on filters) and two comparative CT quantification models
      (DeltaCT and DeltaDeltaCT). Reference materials exerted the biggest influence,
      consistently affecting results by approximately 0.5 log(10) unit. Platform had
      the smallest effect, generally exerting <0.1 log(10) unit difference in final
      results. Quantification model led to small differences (0.04-0.2 log(10) unit) in
      this study with relatively uninhibited samples, but has the potential to cause as
      much as 8-fold (0.9 log(10) unit) difference in potentially inhibitory samples.
      Our findings indicate the need for a certified and centralized source of
      reference materials and additional studies to assess applicability of the
      quantification models in analyses of PCR inhibitory samples.

PMID- 23123049
TI  - Struvite precipitation from urine with electrochemical magnesium dosage.
AB  - When magnesium is added to source-separated urine, struvite (MgNH(4)PO(4).6H(2)O)
      precipitates and phosphorus can be recovered. Up to now, magnesium salts have
      been used as the main source of magnesium. Struvite precipitation with these
      salts works well but is challenging in decentralized reactors, where high
      automation of the dosage and small reactor sizes are required. In this study, we
      investigated a novel approach for magnesium dosage: magnesium was
      electrochemically dissolved from a sacrificial magnesium electrode. We
      demonstrated that this process is technically simple and economically feasible
      and thus interesting for decentralized reactors. Linear voltammetry and batch
      experiments at different anode potentials revealed that the anode potential must
      be higher than -0.9 V vs. NHE (normal hydrogen electrode) to overcome the strong
      passivation of the anode. An anode potential of -0.6 V vs. NHE seemed to be
      suitable for active magnesium dissolution. For 13 subsequent cycles at this
      potential, we achieved an average phosphate removal rate of 3.7 mg P cm(-2) h(
      1), a current density of 5.5 mA cm(-2) and a current efficiency of 118%. Some
      magnesium carbonate (nesquehonite) accumulated on the anode surface; as a
      consequence, the current density decreased slightly, but the current efficiency
      was not affected. The energy consumption for these experiments was 1.7 W h g P(
      1). A cost comparison showed that sacrificial magnesium electrodes are
      competitive with easily soluble magnesium salts such as MgCl(2) and MgSO(4), but
      are more expensive than dosing with MgO. Energy costs for the electrochemical
      process were insignificant. Dosing magnesium electrochemically could thus be a
      worthwhile alternative to dosing magnesium salts. Due to the simple reactor and
      handling of magnesium, this may well be a particularly interesting approach for
      decentralized urine treatment.

PMID- 23123050
TI  - Distribution variation of a metabolic uncoupler, 2,6-dichlorophenol (2,6-DCP) in
      long-term sludge culture and their effects on sludge reduction and biological
      inhibition.
AB  - Distribution variation of a metabolic uncoupler, 2,6-dichlorophenol (2,6-DCP), in
      long-term sludge culture was studied, and the effects on sludge reduction and
      biological inhibition of this chemical during the 90-day operation were
      established. The extracellular polymeric substance (EPS) matrix functioned as a
      protective barrier for the bacteria inside sludge flocs to 2,6-DCP, resulting in
      the transfer of 2,6-DCP from the liquid phase to the activated sludge fraction.
      Significant sludge reduction (about 40%) was observed after the addition of 2,6
      DCP in the first 40 days, while the ineffective function of 2,6-DCP in sludge
      reduction (days 70-90) might be correlated to the EPS protection mechanism. The
      inhibitory effect of 2,6-DCP on the COD removal was extremely lower than on the
      nitrification performance due to the fact that 2,6-DCP was much more toxic to
      autotrophic microorganisms than heterotrophic microorganisms. Moreover, both of
      them recovered to a higher level again with the transfer potential of 2,6-DCP to
      sludge. Thus, the application of metabolic uncoupler for excess sludge reduction
      should be cautious.

PMID- 23123051
TI  - Influence of humic acid on the colloidal stability of surface-modified nano zero
      valent iron.
AB  - To enhance colloidal stability of nano zero-valent iron (NZVI) used for
      groundwater remediation, the surfaces of such NZVI can be modified via coating
      with organic stabilizers. These surface stabilizers can electrostatically,
      sterically, or electrosterically stabilize NZVI suspensions in water, but their
      efficacy is affected by the presence of humic acid (HA) in groundwater. In this
      study, the effect of HA on the colloidal stability of NZVI coated with three
      types of stabilizers (i.e., polyacrylic acid (PAA), Tween-20 and starch) was
      evaluated. Differing stability behaviors were observed for different surface
      modified NZVIs (SM-NZVI) in the presence of HA. Fluorescence spectroscopic
      analysis probed the possible interactions at the SM-NZVI-HA interface, providing
      a better understanding of the effect of HA on SM-NZVI stability. The adsorption
      of HA on the surface of PAA-modified NZVI via complexation with NZVI (rather than
      the PAA stabilizer) enhanced the electrosteric repulsion effect, increasing the
      stability of the particles. However, for NZVI modified with Tween-20 or starch,
      HA could interact with the surface stabilizer and apparently play a "bridge" role
      among the particles, which might induce aggregation of the particles. Therefore,
      the stability behavior of NZVI modified with Tween-20 or starch might have
      resulted from the combined effect of "bridging" and "electrosteric" exerted by
      HA.

PMID- 23123052
TI  - Mechanisms for removal of perfluorooctane sulfonate (PFOS) and perfluorooctanoate
      (PFOA) from drinking water by conventional and enhanced coagulation.
AB  - Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) are persistent
      organic pollutants that have been found to be ubiquitous in the environment. This
      article, for the first time, delineates removal areas of these polar compounds on
      a coagulation diagram that associates chemical conditions with different
      coagulation mechanisms. Variables considered were solution pH, coagulant dosage,
      coagulants (alum and ferric chloride), natural organic matter (NOM), initial
      turbidity, and flocculation time. The jar-test results show that conventional
      coagulation (alum dosage of 10-60 mg/L and final pH of 6.5-8.0) removed <=20% of
      PFOS and PFOA. These chemicals tended to be removed better by enhanced
      coagulation at higher coagulant dosages (>60 mg/L) and (thus) lower final pH (4.5
      6.5). A coagulation diagram was developed to define the coagulant dosage and
      solution pH for PFOS/PFOA removal. The results suggest that the primary PFOS/PFOA
      removal mechanism is adsorption to fine Al hydroxide flocs freshly formed during
      the initial stage of coagulation; increasing flocculation time from 2 to 90 min
      could not further improve PFOS and PFOA removals. Furthermore, the effect of NOM
      on PFOS/PFOA removal by coagulation was examined, and possible removal mechanisms
      were discussed.

PMID- 23123053
TI  - Regulation of the brain-gut axis by group III metabotropic glutamate receptors.
AB  - L-glutamate is produced by a great variety of peripheral tissues in both health
      and disease. Like other components of the glutamatergic system, metabotropic
      glutamate (mGlu) receptors also have a widespread distribution outside the
      central nervous system (CNS). In particular, group III mGlu receptors have been
      recently found in human stomach and colon revealing an extraordinary potential
      for these receptors in the treatment of peripheral disorders, including
      gastrointestinal dysfunction. The significance of these findings is that
      pharmacological tools originally designed for mGlu receptors in the CNS may also
      be directed towards new disease targets in the periphery. Targeting mGlu
      receptors can also be beneficial in the treatment of disorders involving central
      components together with gastrointestinal dysfunction, such as irritable bowel
      syndrome, which can be co-morbid with anxiety and depression. Conversely, the
      development of more specific therapeutic approaches for mGlu ligands both
      centrally as in the gut will depend on the elucidation of tissue-specific
      elements in mGlu receptor signalling.

PMID- 23123054
TI  - Denbinobin induces human glioblastoma multiforme cell apoptosis through the
      IKKalpha-Akt-FKHR signaling cascade.
AB  - Denbinobin, a phenanthraquinone derivative, was shown to exert antitumor
      activities in several types of cancer cell lines. However, the precise mechanism
      underlying denbinobin-induced cell death remains unclear. In this study, we
      investigated the apoptotic signaling cascade elicited by denbinobin in human
      glioblastoma multiforme (GBM) cells. Denbinobin concentration-dependently caused
      a decrease in the cell viability of GBM cells. A flow cytometric analysis of
      propidium iodide (PI)-stained cells demonstrated that denbinobin induced GBM cell
      apoptosis. Denbinobin evoked caspase-3 activation and degradation of poly (ADP
      ribose) polymerase (PARP) and N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone
      (zVAD-fmk), a broad-spectrum caspase inhibitor that prevented denbinobin-induced
      cell death. In addition, denbinobin-induced cell death was diminished by the
      transfection of wild-type (WT) Akt or IkappaB kinase (IKK) into GBM cells.
      Denbinobin reduced IKK phosphorylation in a time-dependent manner, and denbinobin
      dephosphorylated IKK was accompanied by a decrease in Akt phosphorylation. The
      phosphorylation status of forkhead in rhabdomyosarcoma (FKHR), a downstream
      signal molecule of Akt, was also diminished by the presence of denbinobin.
      Furthermore, transfection of GBM cells with WT IKKalpha markedly suppressed the
      decreases in Akt and FKHR phosphorylation caused by denbinobin. In contrast,
      transfection with WT IKKbeta only slightly affected denbinobin's action against
      IKK, Akt, and FKHR. These results suggest that IKKalpha inactivation, followed by
      Akt and FKHR dephosphorylation and caspase-3 activation, contributes to
      denbinobin-induced GBM cell apoptosis.

PMID- 23123055
TI  - Protective effect of 2-hydroxy-4-methoxy benzoic acid on testosterone induced
      benign prostatic hyperplasia in Wister rats.
AB  - Oxidative stress is one of the major causative factors for development of benign
      prostatic hyperplasia (BPH). The aim of the present study is to evaluate the
      effect of 2-hydroxy-4-methoxy benzoic acid (HMBA), a potential antioxidant on
      testosterone induced BPH in rats. Male Wistar rats were divided into five groups
      (n=6), Group I--received saline, Group II--received testosterone (3mg/kg/s.c.),
      Group III-received testosterone+finasteride (5mg/kg/oral), Group IV and V
      received testosterone+HMBA (200 and 400 MUg/kg/i.p.), respectively, for 21 days.
      Animals were weighed before and after the study period. On 22nd day, animals were
      humanly killed by cervical dislocation. Prostates were excised and weighed, and
      used for biochemical and histological studies. As a result, testosterone treated
      rats showed increased prostate weight; prostatic index accompanied with depleted
      antioxidant enzymes levels, elevated lipid peroxides and total nitrite and
      associated histology disruption. HMBA treatment at 200 MUg/kg/i.p. and 400
      MUg/kg/i.p. significantly restored (P<0.05) antioxidant enzyme levels, lipid
      peroxide and total nitrite when compared to disease control animals. It also
      ameliorated the testosterone induced histological changes. The present study
      suggests the protective role of HMBA on testosterone induced BPH by virtue of its
      antioxidant potential.

PMID- 23123056
TI  - Antihypertensive effect of formononetin through regulating the expressions of
      eNOS, 5-HT2A/1B receptors and alpha1-adrenoceptors in spontaneously rat arteries.
AB  - One of the main pathological changes of hypertension is the dysfunction of blood
      vessels. We have found in our previous study that formononetin, one kind of
      phytoestrogens, has an acute antihypertensive effect. Therefore, we hypothesized
      that formononetin might produce a chronic antihypertensive effect through
      regulating the expressions of contractile receptors and endothelial nitric oxide
      synthase (eNOS) in artery. The present study was conducted to verify this effect.
      Male spontaneously hypertensive rats (SHRs) were divided into two groups, orally
      administrated formononetin (50mg/kg per day) and Tween 80 vehicle, respectively,
      for 8 weeks. The blood pressure was measured by tail-cuff method. Isometric
      tension of arterial rings was recorded by a myograph system. The mRNA and protein
      expression in arteries was determined with quantitative real-time polymerase
      chain reaction and immunohistochemistry, respectively. Results showed that the
      systolic blood pressure of SHRs decreased significantly in formononetin group
      compared to Tween 80 group. The vasoconstriction induced by phenylephrine or 5
      hydroxytryptamine (5-HT) in the mesenteric artery segments in formononetin group
      was decreased, and the relaxation induced by acetylcholine was increased compared
      with that in Tween 80 group. In the mesenteric arteries of the formononetin
      treated SHRs, the expressions of alpha(1)-adrenoceptors and 5-HT(2A/1B) receptors
      at both mRNA and protein levels decreased, while the mRNA and protein expressions
      of eNOS increased. In conclusion, formononetin has a chronic antihypertensive
      effect in SHRs. The antihypertensive mechanism may be associated with the down
      regulation of alpha(1)-adrenoceptors and 5-HT(2A/1B) receptors, and the up
      regulation of eNOS expression in arteries.

PMID- 23123057
TI  - Excitotoxicity: bridge to various triggers in neurodegenerative disorders.
AB  - Glutamate is one of the most prominent neurotransmitter in the body, present in
      over 50% of nervous tissue and plays an important role in neuronal excitation.
      This neuronal excitation is short-lived and is followed by depression. Multiple
      abnormal triggers such as energy deficiency, oxidative stress, mitochondrial
      dysfunction, calcium overload, etc can lead to aberration in neuronal excitation
      process. Such an aberration, serves as a common pool or bridge between abnormal
      triggers and deleterious signaling processes with which central neurons cannot
      cope up, leading to death. Excitotoxicity is the pathological process by which
      nerve cells are damaged and killed by excessive stimulation by neurotransmitters
      such as glutamate and similar substances. Such excitotoxic neuronal death has
      been implicated in spinal cord injury, stroke, traumatic brain injury, hearing
      loss and in neurodegenerative diseases of the central nervous system such as
      stroke, epilepsy, multiple sclerosis, Alzheimer disease, Amyltropic lateral
      sclerosis, Parkinson's disease, Huntington disease and alcohol withdrawal. This
      review mainly emphasizes the triggering events which sustain neuronal excitation,
      role of calcium, mitochondrial dysfunction, ROS, NO, chloride homeostasis and
      eicosanoids pathways. Further, a brief introduction about the recent research
      occurring in the treatment of various neurodegenerative diseases, including a
      summary of the presumed physiologic mechanisms behind the pharmacology of these
      disorders.

PMID- 23123058
TI  - Aortic root replacement for ascending aortic disease: a 10 year review.
AB  - BACKGROUND: Bentall's procedure and its modifications have been used for over 40
      years for the treatment of ascending aortic disease. This study reviewed 10 years
      of experience with Aortic Root Replacement (ARR) in a major cardiac surgical
      centre. METHODS: Eighty-nine patients underwent ARR between 1999 and 2009. The
      records were scrutinised by retrospective chart review. RESULTS: The mean age was
      54 years. Seventy-nine percent of patients were male and 21% female. The
      indications for the procedure were Aortic Root Aneurysm (ARA) (65%), type A
      dissection (28%), infective endocarditis (4.4%) and prosthetic valve
      regurgitation (2.2%). Fifty-seven percent of these were performed electively and
      43% as an emergency. A bicuspid aortic valve was present in 37%. Arch surgery was
      required in 15.7%, bypass grafting in 12.3% and mitral valve surgery in 5.6%. The
      descending aorta was involved in 16.8%. Operative mortality was 3.3% and in
      hospital mortality 12.3%. Mean follow-up was 67.05 months (range 2-143). No
      patients required re-operation. CONCLUSIONS: The factors associated with
      increased in-hospital mortality were pre-operative haemodynamic instability,
      concommitant coronary artery disease and acute renal failure. The presence of a
      bicuspid valve may be associated with lower rates of complications, but no
      difference in mortality.

PMID- 23123059
TI  - Suprascapular nerve palsy following supraclavicular block for upper extremity
      surgery: report of 3 cases.
AB  - Regional anesthesia has become the preferred method of anesthesia for many upper
      extremity operations and generally results in decreased hospital stays,
      postoperative opioid requirement, and postoperative nausea. Complications of
      regional anesthesia are rarely reported in the literature, possibly because of
      limited anesthesiologist-patient follow-up. Three cases of suprascapular nerve
      palsy after ultrasound-guided supraclavicular nerve block for routine outpatient
      upper extremity surgery are reported. All cases occurred in men who originally
      presented with shoulder pain, which resolved with time, followed by weakness in
      the supraspinatus and infraspinatus, which improved over time but did not
      resolve. One case resulted in ipsilateral phrenic nerve palsy as well. A review
      of the literature on the subject accompanies the report of these 3 cases.

PMID- 23123060
TI  - T cell receptor stimulation-induced epigenetic changes and Foxp3 expression are
      independent and complementary events required for Treg cell development.
AB  - The transcription factor Foxp3 is essential for the development of regulatory T
      (Treg) cells, yet its expression is insufficient for establishing the Treg cell
      lineage. Here we showed that Treg cell development was achieved by the
      combination of two independent processes, i.e., the expression of Foxp3 and the
      establishment of Treg cell-specific CpG hypomethylation pattern. Both events were
      induced by T cell receptor stimulation. The Treg cell-type CpG hypomethylation
      began in the thymus and continued to proceed in the periphery and could be fully
      established without Foxp3. The hypomethylation was required for Foxp3(+) T cells
      to acquire Treg cell-type gene expression, lineage stability, and full
      suppressive activity. Thus, those T cells in which the two events have
      concurrently occurred are developmentally set into the Treg cell lineage. This
      model explains how Treg cell fate and plasticity is controlled and can be
      exploited to generate functionally stable Treg cells.

PMID- 23123061
TI  - The short isoform of the CEACAM1 receptor in intestinal T cells regulates mucosal
      immunity and homeostasis via Tfh cell induction.
AB  - Carcinoembryonic antigen cell adhesion molecule like I (CEACAM1) is expressed on
      activated T cells and signals through either a long (L) cytoplasmic tail
      containing immune receptor tyrosine based inhibitory motifs, which provide
      inhibitory function, or a short (S) cytoplasmic tail with an unknown role.
      Previous studies on peripheral T cells show that CEACAM1-L isoforms predominate
      with little to no detectable CEACAM1-S isoforms in mouse and human. We show here
      that this was not the case in tissue resident T cells of intestines and gut
      associated lymphoid tissues, which demonstrated predominant expression of CEACAM1
      S isoforms relative to CEACAM1-L isoforms in human and mouse. This tissue
      resident predominance of CEACAM1-S expression was determined by the intestinal
      environment where it served a stimulatory function leading to the regulation of T
      cell subsets associated with the generation of secretory IgA immunity, the
      regulation of mucosal commensalism, and defense of the barrier against
      enteropathogens.

PMID- 23123062
TI  - Interleukin-17 cytokines are critical in development of fatal lupus
      glomerulonephritis.
AB  - Systemic lupus erythematosus is a potentially fatal autoimmune disease. Although
      interleukin-17 (IL-17) has been linked to human lupus and mouse models of this
      disease, it has not been addressed whether this cytokine plays a critical role in
      fatal lupus pathology. Here we have demonstrated that increased production of IL
      17 cytokines and their signaling via the adaptor protein CIKS (a.k.a. Traf3ip2,
      Act1) critically contributed to lethal pathology in an FcgammaR2b-deficient mouse
      model of lupus. Mice lacking IL-17 and especially those lacking CIKS showed
      greatly improved survival and were largely protected from development of
      glomerulonephritis. Importantly in this model, potential effects of IL-17
      cytokines on antibody production could be distinguished from critical local
      contributions in kidneys, including recruitment of neutrophils and monocytes.
      These findings provide the proof of principle that signaling by IL-17 family
      cytokines mediated via CIKS presents promising therapeutic targets for the
      treatment of systemic lupus erythematosus, especially in cases with kidney
      involvement.

PMID- 23123063
TI  - CXCR3 chemokine receptor-ligand interactions in the lymph node optimize CD4+ T
      helper 1 cell differentiation.
AB  - Differentiation of naive CD4(+) T cells into T helper (Th) cells is a defining
      event in adaptive immunity. The cytokines and transcription factors that control
      Th cell differentiation are understood, but it is not known how this process is
      orchestrated within lymph nodes (LNs). Here we have shown that the CXCR3
      chemokine receptor was required for optimal generation of interferon-gamma (IFN
      gamma)-secreting Th1 cells in vivo. By using a CXCR3 ligand reporter mouse, we
      found that stromal cells predominately expressed the chemokine ligand CXCL9
      whereas hematopoietic cells expressed CXCL10 in LNs. Dendritic cell (DC)-derived
      CXCL10 facilitated T cell-DC interactions in LNs during T cell priming while both
      chemokines guided intranodal positioning of CD4(+) T cells to interfollicular and
      medullary zones. Thus, different chemokines acting on the same receptor can
      function locally to facilitate DC-T cell interactions and globally to influence
      intranodal positioning, and both functions contribute to Th1 cell
      differentiation.

PMID- 23123064
TI  - The receptor LMIR3 negatively regulates mast cell activation and allergic
      responses by binding to extracellular ceramide.
AB  - Mast cells (MCs) are key effector cells in allergic reactions. However, the
      inhibitory mechanism that prevents excessive activation of MCs remains elusive.
      Here we show that leukocyte mono-immunoglobulin-like receptor 3 (LMIR3; also
      called CD300f) is a negative regulator of MC activation in vivo. LMIR3 deficiency
      exacerbated MC-dependent allergic responses in mice, including anaphylaxis,
      airway inflammation, and dermatitis. Both physical binding and functional
      reporter assays via an extracellular domain of LMIR3 showed that several
      extracellular lipids (including ceramide) and lipoproteins were possible ligands
      for LMIR3. Importantly, MCs were frequently surrounded by extracellular ceramide
      in vivo. Upon engagement of high-affinity immunoglobulin E receptor,
      extracellular ceramide-LMIR3 binding inhibited MC activation via immunoreceptor
      tyrosine-based inhibitory and switch motifs of LMIR3. Moreover, pretreatment with
      LMIR3-Fc fusion protein or antibody against either ceramide or LMIR3 interfered
      with this binding in vivo, thereby exacerbating passive cutaneous anaphylaxis.
      Thus, the interaction between extracellular ceramide and LMIR3 suppressed MC
      dependent allergic responses.

PMID- 23123065
TI  - Effect of experimental photopolymerized coatings on the hydrophobicity of a
      denture base acrylic resin and on Candida albicans adhesion.
AB  - OBJECTIVE: This study investigated the effect of experimental photopolymerized
      coatings, containing zwitterionic or hydrophilic monomers, on the hydrophobicity
      of a denture base acrylic resin and on Candida albicans adhesion. METHODS:
      Acrylic specimens were prepared with rough and smooth surfaces and were either
      left untreated (control) or coated with one of the following experimental
      coatings: 2-hydroxyethyl methacrylate (HE); 3-hydroxypropyl methacrylate (HP);
      and 2-trimethylammonium ethyl methacrylate chloride (T); and sulfobetaine
      methacrylate (S). The concentrations of these constituent monomers were 25%, 30%
      or 35%. Half of the specimens in each group (control and experimentals) were
      coated with saliva and the other half remained uncoated. The surface free energy
      of all specimens was measured, regardless of the experimental condition. C.
      albicans adhesion was evaluated for all specimens, both saliva conditioned and
      unconditioned. The adhesion test was performed by incubating specimens in C.
      albicans suspensions (1*10(7)cell/mL) at 37 degrees C for 90min. The number of
      adhered yeasts were evaluated by XTT (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-5
      [{phenylamino}carbonyl]-2H-tetrazolium-hydroxide) method. RESULTS: For rough
      surfaces, coatings S (30 or 35%) and HP (30%) resulted in lower absorbance values
      compared to control. These coatings exhibited more hydrophilic surfaces than the
      control group. Roughness increased the adhesion only in the control group, and
      saliva did not influence the adhesion. The photoelectron spectroscopy analysis
      (XPS) confirmed the chemical changes of the experimental specimens, particularly
      for HP and S coatings. CONCLUSIONS: S and HP coatings reduced significantly the
      adhesion of C. albicans to the acrylic resin and could be considered as a
      potential preventive treatment for denture stomatitis.

PMID- 23123066
TI  - In silico model of drug permeability across sublingual mucosa.
AB  - The objective of this work was to develop an in silico model to predict the
      sublingual permeability of a drug based on physicochemical descriptors of a
      molecule. Fourteen model drugs with diverse physicochemical properties were
      selected for this study. Molecular volume, molecular weight, logP, logD (pH 6.8),
      pKa, total polar surface area, hydrogen bond acceptors and donors (HBD), number
      of rotatable bonds, solubility (pH 6.8), and melting point were used as molecular
      descriptors. Apparent permeability coefficients (Pe) of drugs across porcine
      sublingual mucosa were determined experimentally. Multiple linear regression
      (MLR) was used to develop the model with permeability as the response variable
      and various descriptors as the predictive variables. Q(2), the cross-validated
      correlation coefficient, was used to assess the prediction ability of the model.
      MLR analysis showed that HBD and logD were the significant descriptors (P<0.05,
      Q(2)=0.88) in the sublingual permeability model. The resulting model is expressed
      as the following equation:An excellent fit with R(2) of 0.93 was obtained between
      experimental and predicted permeabilities. The analysis of contributions of
      molecular descriptors to sublingual permeability revealed the molecular structure
      basis of permeation across sublingual mucosa. In conclusion, an in silico model
      was developed to predict sublingual permeability of drugs using known descriptors
      for evaluating the feasibility of sublingual drug delivery.

PMID- 23123067
TI  - Micro-architecture and mineralization of the human alveolar bone obtained with
      microCT.
AB  - OBJECTIVES: The primary dental implant stability depends on the location of the
      implant in the jaw. This study analysed the architecture and mineralization of
      the trabecular bone at different jaw locations and thereby identified potential
      prognostic factors for implant failure. It has checked the hypotheses: (1) the
      mandible contains more compact and less mineralized trabecular bone than the
      maxilla and (2) within the mandible the trabecular bone is more compact and less
      mineralized in the anterior region. METHODS: Alveolar bone specimens were
      produced from the cadavers of ten humans (7 males and 3 females; mean age: 73.7+/
      12.5 years) and scanned with a high-resolution microCT system. Volumes of
      interest were chosen next to the roots of molars and incisors in both the maxilla
      and mandible. Several morphological parameters as well as the tissue mineral
      density were determined. RESULTS: The alveolar bone specimens had a very high
      bone volume fraction (mean=0.31) with large differences (SD=0.17) between and
      within subjects. Yet several significant differences were found between the
      maxilla and the mandible. The bone volume fraction and trabecular thickness were
      significantly higher in the mandible than in the maxilla (p<0.01). But the tissue
      mineral density was not significantly different. CONCLUSIONS: A higher primary
      implant stability coincides with a higher bone volume fraction and degree of
      anisotropy Although local differences remain more important for implantology, the
      results suggest that the micro-structure also affects the implant stability. The
      tissue mineral density seems to have no predictive value.

PMID- 23123068
TI  - Factors associated with specific clinical forms of oral candidiasis in HIV
      infected Brazilian adults.
AB  - OBJECTIVE: This study assesses the association among factors related with
      specific clinical forms of oral candidiasis (OC) in HIV-infected Brazilian
      adults. DESIGN: This study was conducted with 590 HIV-infected adults from 1997
      to 2004. The OC diagnosis was based in accordance with the EC-Clearinghouse
      classification. Multivariate logistic regression analyses were performed to
      measure the association between HAART and OC, with pseudomembranous [PC],
      erythematous [EC], and angular cheilitis [AC]) adjusted for HIV-related diseases,
      smoking, alcohol consumption, injecting and non-injecting drug use. RESULTS: Two
      hundred and eighteen (37.0%) individuals were undergoing HAART. The prevalence of
      PC, EC and AC was 21.2%, 15.7% and 8.8%, respectively. Approximately 64% of the
      individuals with PC and EC, and 76.5% with AC had absolute CD4 levels
      <=200cells/mm(3). The results of the multivariate analysis showed that subjects
      not undergoing HAART had a significantly higher odds ratio for PC [OR 3.67 (95%
      CI: 1.97-6.80)] and EC [OR 1.88 (95% CI: 1.04-3.39)], and AC [OR 4.56 (95% CI:
      1.58-13.19)]. In addition, smoking [OR 2.58 (95% CI: 1.43-4.68)] and pneumocystis
      pneumonia [OR 1.92 (95% CI: 1.07-3.42)] were associated with PC, while high
      alcohol consumption [OR 3.40 (95% CI: 1.13-10.18)] and cytomegalovirus infection
      [OR 2.34 (95% CI: 1.06-5.15)] were associated with EC. CONCLUSION: The data
      indicates that the odds of having all clinical forms of OC are higher in HIV
      infected adults not receiving HAART.

PMID- 23123069
TI  - Cytotoxicity and proliferative effects of Iodoform-containing root canal-filling
      material on RAW 264.7 macrophage and RKO epithelial cell lines.
AB  - OBJECTIVE: The present study investigated the effect of the Iodoform-containing
      root canal filling material on the viability of cultured macrophages and
      epithelial cells, and on cytokine secretion. DESIGN: The effect of Endoflas F.S.
      on the proliferation of a RAW 264.7 macrophage cell line and on a RKO epithelial
      cell line, and on the production of tumour necrosis factor alpha (TNFalpha) from
      macrophages was examined. Cell vitality was evaluated using a colourimetric XTT
      (sodium 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)-carbonyl]-2H
      tetrazolium inner salt) assay. The presence of cytokines was determined by two
      site enzyme-linked immunosorbent assay (ELISA). RESULTS: Direct exposure of
      Endoflas F.S. and its media, up to a dilution of 1/8, decreased the viability of
      macrophages and epithelial cells by ~70% compared to control media (P<0.05).
      Media dilution from 1/16 to 1/1024 demonstrated a proliferative effect,
      increasing cell viability by about 60% compared to media without Iodoform
      containing root canal filling material. CONCLUSIONS: Direct and indirect exposure
      to high concentrations of iodoform-containing root canal filling material showed
      a cytotoxic effect on macrophages and epithelial cells, while low concentrations
      induced cell proliferation.

PMID- 23123070
TI  - Evaluating the efficiency of caries removal using an Er:YAG laser driven by
      fluorescence feedback control.
AB  - INTRODUCTION: Caries lesions in dental hard tissues autofluoresce when exposed to
      light of certain wavelengths, whereas sound tissues do not, and this can be used
      as an in vitro histological marker for dental caries. Detection of
      autofluorescence is the basis of KaVo DIAGNOdentTM technology, and provides
      objective feedback control of laser-stimulated ablation of dental caries for the
      KaVo Key Laser 3TM. This Er:YAG laser operates at 2940nm wavelength, and is
      effective at removal of infected dental hard tissues. Micro-computed tomography
      (micro-CT) allows the non-invasive investigation of three-dimensional structures
      and analysis of mineral density profiles of dentine following laser ablation.
      OBJECTIVE: To evaluate removal of infected, demineralised dentine by Er:YAG
      irradiation with a laser feedback mechanism, using micro-CT. DESIGN: 27 carious
      teeth (1 control) and 1 sound tooth, treated with the KaVo Key Laser 3TM using a
      KaVoTM non-contact 2060 handpiece at specific feedback settings, were examined
      using a Skyscan 1172 Micro-CT, to observe the efficiency of demineralised dentine
      removal. Grey scale images obtained were colour rendered to assist detection of
      demineralised tissue if present. RESULTS: Complete removal of demineralised
      tissue occurred with laser-stimulated ablation under feedback control at values
      of 7 and 8 when measured by micro-CT. At greater values, removal of demineralised
      dentine was incomplete. CONCLUSION: Examination of dental tissues by micro-CT
      allowed determination of the efficiency of Er:YAG laser-stimulated ablation.
      Feedback control of the KaVo Key Laser 3TM appeared to operate like a cut-off
      switch when infected dentine was eliminated, at a threshold of between 6 and 7.

PMID- 23123072
TI  - Setting realistic expectations for DBS in dystonia.

PMID- 23123073
TI  - A system to measure the kinematics during the entire ski jump sequence using
      inertial sensors.
AB  - Three-dimensional analysis of the entire sequence in ski jumping is recommended
      when studying the kinematics or evaluating performance. Camera-based systems
      which allow three-dimensional kinematics measurement are complex to set-up and
      require extensive post-processing, usually limiting ski jumping analyses to small
      numbers of jumps. In this study, a simple method using a wearable inertial
      sensors-based system is described to measure the orientation of the lower-body
      segments (sacrum, thighs, shanks) and skis during the entire jump sequence. This
      new method combines the fusion of inertial signals and biomechanical constraints
      of ski jumping. Its performance was evaluated in terms of validity and
      sensitivity to different performances based on 22 athletes monitored during daily
      training. The validity of the method was assessed by comparing the inclination of
      the ski and the slope at landing point and reported an error of -0.2+/-4.8
      degrees . The validity was also assessed by comparison of characteristic angles
      obtained with the proposed system and reference values in the literature; the
      differences were smaller than 6 degrees  for 75% of the angles and smaller than
      15 degrees  for 90% of the angles. The sensitivity to different performances was
      evaluated by comparing the angles between two groups of athletes with different
      jump lengths and by assessing the association between angles and jump lengths.
      The differences of technique observed between athletes and the associations with
      jumps length agreed with the literature. In conclusion, these results suggest
      that this system is a promising tool for a generalization of three-dimensional
      kinematics analysis in ski jumping.

PMID- 23123071
TI  - Pallidal deep brain stimulation in patients with primary generalised or segmental
      dystonia: 5-year follow-up of a randomised trial.
AB  - BACKGROUND: Severe forms of primary dystonia are difficult to manage medically.
      We assessed the safety and efficacy of pallidal neurostimulation in patients with
      primary generalised or segmental dystonia prospectively followed up for 5 years
      in a controlled multicentre trial. METHODS: In the parent trial, 40 patients were
      randomly assigned to either sham neurostimulation or neurostimulation of the
      internal globus pallidus for a period of 3 months and thereafter all patients
      completed 6 months of active neurostimulation. 38 patients agreed to be followed
      up annually after the activation of neurostimulation, including assessments of
      dystonia severity, pain, disability, and quality of life. The primary endpoint of
      the 5-year follow-up study extension was the change in dystonia severity at 3
      years and 5 years as assessed by open-label ratings of the Burke-Fahn-Marsden
      dystonia rating scale (BFMDRS) motor score compared with the preoperative
      baseline and the 6-month visit. The primary endpoint was analysed on an intention
      to-treat basis. The original trial is registered with ClinicalTrials.gov
      (NCT00142259). FINDINGS: An intention-to-treat analysis including all patients
      from the parent trial showed significant improvements in dystonia severity at 3
      years and 5 years compared with baseline, which corresponded to -20.8 points (SD
      17.1; -47.9%; n=40) at 6 months; -26.5 points (19.7; -61.1%; n=31) at 3 years;
      and -25.1 points (21.3; -57.8%; n=32). The improvement from 6 months to 3 years (
      5.7 points [SD 8.4]; -34%) was significant and sustained at the 5-year follow-up
      (-4.3 [10.4]). 49 new adverse events occurred between 6 months and 5 years.
      Dysarthria and transient worsening of dystonia were the most common non-serious
      adverse events. 21 adverse events were rated serious and were almost exclusively
      device related. One patient attempted suicide shortly after the 6-month visit
      during a depressive episode. All serious adverse events resolved without
      permanent sequelae. INTERPRETATION: 3 years and 5 years after surgery, pallidal
      neurostimulation continues to be an effective and relatively safe treatment
      option for patients with severe idiopathic dystonia. This long-term observation
      provides further evidence in favour of pallidal neurostimulation as a first-line
      treatment for patients with medically intractable, segmental, or generalised
      dystonia. FUNDING: Medtronic.

PMID- 23123074
TI  - Consideration of equilibrium equations at the hip joint alongside those at the
      knee and ankle joints has mixed effects on knee joint response during gait.
AB  - Accurate estimation of muscle forces during daily activities such as walking is
      critical for a reliable evaluation of loads on the knee joint. To evaluate knee
      joint muscle forces, the importance of the inclusion of the hip joint alongside
      the knee and ankle joints when treating the equilibrium equations remains yet
      unknown. An iterative kinematics-driven finite element model of the knee joint
      that accounts for the synergy between passive structures and active musculature
      is employed. The knee joint muscle forces and biomechanical response are
      predicted and compared with our earlier results that did not account for moment
      equilibrium equations at the hip joint. This study indicates that inclusion of
      the hip joint in the optimization along the knee and ankle joints only slightly
      (<10%) influences total forces in quadriceps, lateral hamstrings and medial
      hamstrings. As a consequence, even smaller differences are found in predicted
      ligament forces, contact forces/areas, and cartilage stresses/strains during the
      stance phase of gait. The distribution of total forces between the uni- and bi
      articular muscle components in quadriceps and in lateral hamstrings; however,
      substantially alter at different stance phases.

PMID- 23123075
TI  - Fibrin polymerization in blood coagulation-a statistical model.
AB  - A theoretical model for the growth of fibrin clots is derived. The model is based
      on a statistical description of the polymerization process underlying the
      formation of the fibrin polymeric network. The model provides insights regarding
      the role of various factors, such as thrombin concentration, plasmin
      concentration, and the local shear rate in the coagulation process. In
      particular, the effect of these factors on the mechanical properties of the clot
      is studied. Numerical results are in very good agreement with quantitative and
      qualitative experimental observations. Importantly, no fitting parameters are
      used, and all model parameters, such as fibrin persistence length and monomer
      size, are in accordance with experimental reports.

PMID- 23123076
TI  - Response to letter to the editor: comment on "injectable calcium phosphate cement
      for augmentation around cancellous bone screws. In vivo biomechanical studies"
      (volume 45, issue 7, pages 1156-1160).

PMID- 23123078
TI  - Host endomembrane recruitment for plant RNA virus replication.
AB  - Although there is a significant amount of literature that deals with the
      identification of plant viral proteins involved in membrane remodeling and
      vesicle production in infected cells, there are very few investigations that
      report on the impact that infection has on the overall architecture and dynamics
      of the early secretory endomembranes. Recent investigations have shown that for
      some viruses the endoplasmic reticulum, Golgi bodies and other organelles are
      heavily recruited into virus-induced perinuclear structures. These structures are
      not isolated organelles and are dynamically connected to the bulk of non-modified
      endomembranes. They also have a functional link with peripheral motile vesicles
      involved in virus intracellular movement. The full molecular events that
      consubstantiate with this endomembrane recruitment in virus-induced structures
      remain to be elucidated but viral genome replication and virion assembly are
      probably taking place within these structures.

PMID- 23123079
TI  - [Pelvic inflammatory diseases: guidelines for clinical practice - method and
      organization].

PMID- 23123077
TI  - Effect of chlorination and ultraviolet disinfection on tetA-mediated tetracycline
      resistance of Escherichia coli.
AB  - Antibiotic-resistant bacteria are an emerging threat to public health during
      drinking water consumption and reclaimed water reuse. Several studies have shown
      that the proportions of antibiotic-resistant bacteria in waters may increase when
      exposed to low doses of UV light or chlorine. In this study, inactivation of
      tetracycline-resistant Escherichia coli and antibiotic-sensitive E. coli by UV
      disinfection and chlorination was compared to determine the tolerance of
      tetracycline-resistant E. coli to UV light and chlorine, and tetracycline
      resistance of a tetracycline-resistant E. coli population was studied under
      different doses of the disinfectants. Our results showed that relative to
      antibiotic-sensitive E. coli, tetracycline-resistant E. coli had the same
      tolerance to UV light and a potentially higher tolerance to chlorination. The
      mortality frequency distributions of tetracycline-resistant E. coli exposed to
      tetracycline were shifted by both chlorination and UV disinfection. When compared
      to the hemi-inhibitory concentrations (IC(50)) of tetracycline-resistant E. coli
      with no exposure to UV or chlorination, the IC(50) of tetracycline-resistant E.
      coli treated with tetracycline was 40% lower when inactivation by UV light or
      chlorination reached 3-log but was 1.18 times greater when inactivation by
      chlorination reached 4.3-log. Chlorination applied to drinking water or reclaimed
      water treatment may increase the risk of selection for highly tetracycline
      resistant E. coli.

PMID- 23123080
TI  - [Women with previous caesarean or other uterine scar: epidemiological features].
AB  - OBJECTIVE: To describe the prevalence of uterine scar and the risk of associated
      obstetrical complications and current modes of delivery in women with a previous
      cesarean. METHOD: Consultation of the Medline database, and of the National
      Perinatal Surveys data. RESULTS: Previous cesarean is the main cause of uterine
      scar. In France, the cesarean rate increased from 15.5% in 1995 to 20.8% in 2010;
      as a consequence, the prevalence of previous cesarean also increased from 8 to
      11% of parturients and from 14 to 19% of multiparas, between 1995 and 2010.
      Previous cesarean is, in developed countries, the main risk factor for uterine
      rupture, whose global incidence is estimated between 0.1 and 0.5% in parturients
      with previous cesarean. Women with previous cesarean also are at higher risk for
      abnormal placenta insertion, the strength of the association increasing with the
      number of previous cesareans: twice higher risk of placenta praevia and greater
      maternal morbidity associated with placenta praevia; major risk factor for
      placenta accreta in particular in women combining previous cesarean and placenta
      praevia. Modes of delivery in women with previous cesarean vary widely between
      countries. According to the 2010 National Perinatal Survey, in France, 51% have a
      cesarean before labor; among those with a trial of labor, 75% deliver vaginally;
      in total, 36.5% have a vaginal delivery. CONCLUSION: The prevalence of uterine
      scar is increasing, following the rise in cesarean rate. This condition is a risk
      factor for obstetrical complications in subsequent pregnancies. Women with
      multiple previous cesareans are particularly at risk.

PMID- 23123081
TI  - Enhanced cognitive behaviour therapy for adolescents with anorexia nervosa: an
      alternative to family therapy?
AB  - A specific form of family therapy (family-based treatment) is the leading
      treatment for adolescents with anorexia nervosa. As this treatment has certain
      limitations, alternative approaches are needed. "Enhanced" cognitive behaviour
      therapy (CBT-E) is a potential candidate given its utility as a treatment for
      adults with eating disorder psychopathology. The aim of the present study was to
      establish, in a representative cohort of patients with marked anorexia nervosa,
      the immediate and longer term outcome following CBT-E. Forty-nine adolescent
      patients were recruited from consecutive referrals to a community-based eating
      disorder clinic. Each was offered 40 sessions of CBT-E over 40 weeks from a
      single therapist. Two-thirds completed the full treatment with no additional
      input. In these patients there was a substantial increase in weight together with
      a marked decrease in eating disorder psychopathology. Over the 60-week post
      treatment follow-up period there was little change despite minimal subsequent
      treatment. These findings suggest that CBT-E may prove to be a cost-effective
      alternative to family-based treatment.

PMID- 23123082
TI  - Testicular torsion in the inguinal canal in children.
AB  - OBJECTIVE: To evaluate the management and outcomes of pediatric patients
      presenting with torsion of an undescended testis in the inguinal canal. PATIENTS
      AND METHODS: The case records of 84 children operated on for testicular torsion
      were retrospectively reviewed. The medical records included initial medical
      history, physical examination, operative findings, and the results of follow-up.
      The diagnosis of torsion of undescended testis was made clinically and confirmed
      by a Doppler ultrasound and inguinal canal exploration. RESULTS: Eight children
      were operated following torsion of undescended testis. In four cases the testicle
      was preserved and orchidopexy was performed, while in four cases orchidectomy was
      performed due to testicular gangrene. Mean duration of symptoms, at time of
      surgery, in the orchidopexy group was 6 h and in the orchidectomy group was 50 h.
      At follow-up atrophy of the testis was found in only one patient. CONCLUSION:
      Torsion of an undescended testis is a relatively rare phenomenon that should be
      suspected, diagnosed and treated without delay. This study highlights the
      importance of examination of external genital organs. With improved recognition
      of this entity and earlier referrals of patients with undescended testes by
      primary care physicians, its occurrence might eventually be prevented.

PMID- 23123083
TI  - Re: Kim, et al. Analysis of duplicate presentations accepted at two top
      international pediatric urology meetings. Journal of Pediatric Urology 2012; 8:
      291-5 and editorial comment by Skoog, Journal of Pediatric Urology 2012; 8: 296.

PMID- 23123084
TI  - Ultrastructure of the nephron in the soft-shelled turtle, Pelodiscus sinensis
      (Reptilia, Chelonia, Trionychidae).
AB  - The structure of the nephron in adult soft-shelled turtles (Pelodiscus sinensis)
      was studied by light microscopy, transmission and scanning electron microscopy.
      The kidney contained 5-6 renal lobes. Nephrons of P. sinensis are composed of a
      renal corpuscle (RC) and of a renal tubule that appears divided morphologically
      into five distinct segments: neck segment (NS) (This segment is only present in
      approximately 10% of the nephrons), proximal tubule (PT), intermediate segment
      (IS), distal tubule (DT), and collecting duct (CD). The RCs and most of the
      convoluted DTs lie in the central zone, while the PTs and the CDs lie in the
      peripheral zone of the renal lobe. The renal corpuscle is relatively large with
      especial processes in podocytes and a thick basement membrane. The podocyte
      processes covering a large capillary area can be observed by TEM, and the major
      podocyte processes formed a very specific pattern in SEM. The podocyte processes
      expand to form a flattened network over the whole capillary loops surface, and
      only may observe little filtration slits in glomerular area. The neck segment
      when presentis short and has a relatively narrow lumen, consisting of cuboidal or
      squamous cells. There is a well-developed endocytic-lysosomal apparatus in the
      apical cytoplasm of the PT. The proximal tubule and intermediate segment cells
      show some differences between male and female. It showed that proximal tubule
      cells of male soft-shelt turtle contain lateral intercellular spaces, into which
      extensions of the cell membrane protrude, and the basal cell membrane forms a
      conspicuous labyrinth. Whereas, the basal and lateral cell membranes of the
      female are smooth, and no later-basal intercellular spaces. The differences
      between male and female in the middle segment cells is similar to proximal tubule
      cells. Not previously reported in vertebrate kidneys. The IS is the narrowest
      nephron segment, formed by multiciliated as well as nonciliated cells. In DT
      cells, basolateral interdigitations and infoldings are particularly well
      developed. The CD contains clear cells with numerous secretory granules and dark
      cells with dense mitochondria and an elaborate Golgi complex. This study was
      undertaken in order to disclose specific kidney features in P. sinensis that
      could be related to function. In addition, the ultrastructure of the nephrons in
      P. sinensis are discussed in relation to other turtles and vertebrates.

PMID- 23123085
TI  - Emerging organic contaminant removal depending on primary treatment and
      operational strategy in horizontal subsurface flow constructed wetlands:
      influence of redox.
AB  - This study aimed at assessing the influence of primary treatment (hydrolytic
      upflow sludge blanket (HUSB) reactor vs. conventional settling) and operational
      strategy (alternation of saturated/unsaturated phases vs. permanently saturated)
      on the removal of various emerging organic contaminants (i.e. ibuprofen,
      diclofenac, acetaminophen, tonalide, oxybenzone, bisphenol A) in horizontal
      subsurface flow constructed wetlands. For that purpose, a continuous injection
      experiment was carried out in an experimental treatment plant for 26 days. The
      plant had 3 treatment lines: a control line (settler-wetland permanently
      saturated), a batch line (settler-wetland operated with saturate/unsaturated
      phases) and an anaerobic line (HUSB reactor-wetland permanently saturated). In
      each line, wetlands had a surface area of 2.95 m(2), a water depth of 25 cm and a
      granular medium D(60) = 7.3 mm, and were planted with common reed. During the
      study period the wetlands were operated at a hydraulic and organic load of 25
      mm/d and about 4.7 g BOD/m(2)d, respectively. The injection experiment delivered
      very robust results that show how the occurrence of higher redox potentials
      within the wetland bed promotes the elimination of conventional quality
      parameters as well as emerging microcontaminants. Overall, removal efficiencies
      were always greater for the batch line than for the control and anaerobic lines,
      and to this respect statistically significantly differences were found for
      ibuprofen, diclofenac, oxybenzone and bisphenol A. As an example, ibuprofen,
      whose major removal mechanism has been reported to be biodegradation under
      aerobic conditions, showed a higher removal in the batch line (85%) than in the
      control (63%) and anaerobic (52%) lines. Bisphenol A showed also a great
      dependence on the redox status of the wetlands, finding an 89% removal rate for
      the batch line, as opposed to the control and anaerobic lines (79 and 65%,
      respectively). Furthermore, diclofenac showed a greater removal under a higher
      redox status (70, 48 and 32% in the batch, control and anaerobic lines). Average
      removal efficiencies of acetaminophen, oxybenzone and tonalide were almost >90%
      for the 3 treatment lines. The results of this study indicate that the efficiency
      of horizontal flow constructed wetland systems can be improved by using a batch
      operation strategy. Furthermore, we tentatively identified 4-hydroxy-diclofenac
      and carboxy-bisphenol A as intermediate degradation products. The higher
      abundance of the latter under the batch operation strategy reinforced
      biodegradation as a relevant bisphenol A removal pathway under higher redox
      conditions.

PMID- 23123086
TI  - Photodegradation of naproxen and its photoproducts in aqueous solution at 254 nm:
      a kinetic investigation.
AB  - The kinetics of photodegradation of the non steroidal anti-inflammatory drug
      naproxen (+)-S-2-(6-methoxynaphthalen-2-yl)propanoic acid, an emerging organic
      pollutant, was studied in aqueous solutions under deaerated and aerated
      conditions. The photolysis experiments were carried out under monochromatic
      irradiation (lambda = 254 nm) at pH = 7.0 and T = 25  degrees C. Simplified
      reaction schemes of photodegradation of naproxen are proposed in absence and in
      presence of oxygen respectively. The schemes take into account the photolysis of
      naproxen and its photoproducts and the reactions of the measured species with
      oxygen dissolved in the liquid bulk. According to these schemes, two kinetic
      models were developed which correlate the experimental data, for runs performed
      in absence and in presence of oxygen, with a fair accuracy and allowed to
      estimate the best values for the unknown kinetic parameters. The calculated
      quantum yield of direct photolysis of naproxen under deaerated media is in good
      agreement with the one previously reported. Under aerated conditions, the
      generation of singlet oxygen has also been taken into account. The obtained
      results, under the adopted conditions, indicated a marked influence of dissolved
      oxygen on the photodegradation rates of naproxen and the relative distribution of
      the major reaction intermediates.

PMID- 23123087
TI  - Electrical stimulation of microbial PCB degradation in sediment.
AB  - Bioremediation of polychlorinated biphenyls (PCBs) has been precluded in part by
      the lack of a cost-effective method to stimulate microbial degradation in situ. A
      common limitation is the lack of an effective method of providing electron donors
      and acceptors to promote in situ PCB biodegradation. Application of an electric
      potential to soil/sediment could be an effective means of providing electron
      donors/-acceptors to PCB dechlorinating and degrading microorganisms. In this
      study, electrical stimulation of microbial PCB dechlorination/degradation was
      examined in sediment maintained under simulated in situ conditions. Voltage was
      applied to open microcosms filled with PCB-impacted (Aroclor 1242) freshwater
      sediment from a Superfund site (Fox River, WI). The effect of applied low
      voltages (1.5-3.0 V) on the microbial transformation of PCBs was determined with:
      1) spiked PCBs, and 2) indigenous weathered PCBs. The results indicate that both
      oxidative and reductive microbial transformation of the spiked PCBs was
      stimulated but oxidation was dominant and most effective with higher voltage.
      Chlorobenzoates were produced as oxidation metabolites of the spiked PCBs, but
      increasing voltage enhanced chlorobenzoate consumption, indicating that overall
      degradation was enhanced. In the case of weathered PCBs, the total concentration
      decreased 40-60% in microcosms exposed to electric current while no significant
      decrease of PCB concentration was observed in control reactors (0 V or
      sterilized). Single congener analysis of the weathered PCBs showed significant
      loss of di- to penta-chlorinated congeners, indicating that microbial activity
      was not limited to anaerobic dechlorination of only higher chlorinated congeners.
      Degradation was most apparent with the application of only 1.5 V where anodic
      O(2) was not generated, indicating a mechanism of degradation independent of
      electrolytic O(2). Low voltage stimulation of the microbial degradation of
      weathered PCBs observed in this study suggests that this approach could be a cost
      effective, environmentally sustainable strategy to remediate PCBs in situ.

PMID- 23123088
TI  - Desorption of ciprofloxacin from clay mineral surfaces.
AB  - Desorption from soil clay components may affect the transport and fate of
      antibiotics in the environment. In this study, ciprofloxacin (CIP) desorption
      from a kaolinite and a montmorillonite was investigated under different pHs,
      different concentrations of metal cations of various valencies (Na(+), Ca(2+) and
      Al(3+)) and a cationic surfactant hexadecyltrimethylammonium (HDTMA), and
      different desorption cycles. Desorption of CIP from kaolinite and montmorillonite
      was strongly pH-dependent and desorption isotherms were well fitted with the
      Langmuir equation. The percentage of CIP desorbed increased with increasing
      initial CIP loadings, desorbing cation concentrations, and desorption cycles.
      Comparatively, CIP was more readily desorbed from kaolinite than from
      montmorillonite. Moreover, the hysteresis index values were all negative,
      suggesting that the presence of metal cations and HDTMA in solution promoted CIP
      desorption from clay minerals, owing to cation exchange. The XRD analyses
      indicated that desorption of CIP occurred from both external and interlayer
      surfaces of montmorillonite. Formation of Al-CIP complex on solid surface and
      then detachment of Al-CIP from the solid surface may contribute to the higher CIP
      desorption by Al(3+) in comparison to Na(+) and Ca(2+).

PMID- 23123089
TI  - Personal FM systems for children with autism spectrum disorders (ASD) and/or
      attention-deficit hyperactivity disorder (ADHD): an initial investigation.
AB  - The goal of this initial investigation was to examine the potential benefit of a
      frequency modulation (FM) system for 11 children diagnosed with autism spectrum
      disorders (ASD), attention-deficit hyperactivity disorder (ADHD), or both
      disorders through measures of speech recognition performance in noise, observed
      classroom behavior, and teacher-rated educational risk and listening behaviors.
      Use of the FM system resulted in significant average improvements in speech
      recognition in noise for the children with ASD and ADHD as well as large effect
      sizes. When compared to typically functioning peers, children with ASD and ADHD
      had significantly poorer average speech recognition performance in noise without
      the FM system but comparable average performance when the FM system was used.
      Similarly, classroom observations yielded a significant increase in on-task
      behaviors and large effect sizes when the FM system was in use during two
      separate trial periods. Although teacher ratings on questionnaires showed no
      significant improvement in the average level of educational risk of participants,
      they did indicate significant improvement in average listening behaviors during
      two trial periods with the FM system. Given the significantly better speech
      recognition in noise, increased on-task behaviors, and improved teacher ratings
      of listening behaviors with the FM system, these devices may be a viable option
      for children who have ASD and ADHD in the classroom. However, an individual
      evaluation including audiological testing and a functional evaluation in the
      child's primary learning environment will be necessary to determine the benefit
      of an FM system for a particular student. LEARNING OUTCOMES: 1. The reader will
      be able to describe the potential benefit of FM systems for children with ASD
      and/or ADHD. 2. The reader will be able to identify on-task versus off-task
      listening behaviors in children with ASD and/or ADHD. 3. The reader will be able
      to explain the components of a successful pre-fit education program that may be
      necessary prior to fitting an FM system in children with ASD.

PMID- 23123090
TI  - Effects of orexin A on proliferation, survival, apoptosis and differentiation of
      3T3-L1 preadipocytes into mature adipocytes.
AB  - Metabolic activities of orexin A (OXA) in mature adipocytes are mediated via
      PI3K/PKB and PPARgamma. However, the effects of OXA on preadipocytes are largely
      unknown. We report here that OXA stimulates the proliferation and viability of
      3T3-L1 preadipocytes and protects them from apoptosis via ERK1/2, but not through
      PKB. OXA reduces proapoptotic activity of caspase-3 via ERK1/2. Inhibition of
      ERK1/2 prevents the differentiation of preadipocytes into adipocytes. Unlike
      insulin, neither short-term nor prolonged exposure of 3T3-L1 preadipocytes to OXA
      induces preadipocyte differentiation to adipocytes, despite increased ERK1/2
      phosphorylation. Unlike insulin, OXA fails to activate PKB, which explains its
      inability to induce the differentiation of preadipocytes.

PMID- 23123091
TI  - Involvement of PTEN in TPA-mediated p53-activation in mouse skin epidermal JB6
      cells.
AB  - Our recent studies suggest a unique role of p53 during the early stage of cancer
      development. However, how p53 activation is regulated during TPA treatment
      remains elusive. We used murine skin epidermal JB6 promotion-sensitive (P+) and
      promotion resistant (P-) cells to observe differential expression of PTEN during
      TPA-induced p53 activation. Total PTEN expression was decreased in only P+ cells.
      Nuclear expression of PTEN increased and complex formation between PTEN and p53
      occurred in P+ cells treated with TPA. Knocking down PTEN expression via siRNA
      inhibited TPA-induced Bax expression. Similar effects were seen with the p53
      inhibitor, pifithrin-alpha. Cells that were transfected with siRNA to PTEN
      exhibited enhanced tumorigenicity. Our findings suggest PTEN mediates TPA-induced
      p53 activation.

PMID- 23123092
TI  - Silencing of germline-expressed genes by DNA elimination in somatic cells.
AB  - Chromatin diminution is the programmed elimination of specific DNA sequences
      during development. It occurs in diverse species, but the function(s) of
      diminution and the specificity of sequence loss remain largely unknown.
      Diminution in the nematode Ascaris suum occurs during early embryonic cleavages
      and leads to the loss of germline genome sequences and the formation of a
      distinct genome in somatic cells. We found that ~43 Mb (~13%) of genome sequence
      is eliminated in A. suum somatic cells, including ~12.7 Mb of unique sequence.
      The eliminated sequences and location of the DNA breaks are the same in all
      somatic lineages from a single individual and between different individuals. At
      least 685 genes are eliminated. These genes are preferentially expressed in the
      germline and during early embryogenesis. We propose that diminution is a
      mechanism of germline gene regulation that specifically removes a large number of
      genes involved in gametogenesis and early embryogenesis.

PMID- 23123094
TI  - Triple-barrel graft as a novel strategy to preserve supra-aortic branches in arch
      TEVAR procedures: clinical study and systematic review.
AB  - OBJECTIVE: To report our early experience with total endovascular repair of
      aortic-arch aneurysm using double chimney-grafts and present a literature
      overview. PATIENTS AND METHODS: The double chimney-graft technique was performed
      in six male patients with contained ruptured aneurysm, dissecting aneurysm,
      pseudoaneurysm, penetrating aortic ulcer and proximal endoleak after TEVAR.
      Furthermore, a systematic electronic health database search of available articles
      was conducted according to PRISMA Guidelines. RESULTS: In all cases, all supra
      aortic vessels had to be covered with aortic stent-graft to receive a sufficient
      landing and sealing zone. Chimney-grafts were introduced to the ascending aorta
      slightly deeper than the thoracic stent-grafts through the cut-down exposure of
      the common carotid arteries. We deployed aortic stent-grafts and self-expandable
      chimney-grafts simultaneously and successfully. The patient with contained
      ruptured aneurysm died due to cardiopulmonary failure on day 19, the others
      survived. We detected two 'gutter' endoleaks. As a result of literature search,
      12 articles met the inclusion criteria. Two articles described the double-chimney
      technique. CONCLUSIONS: The use of double chimney-grafts is possible in high-risk
      patients where the proximal landing zone of endograft would be in zone 0. The
      available data is still limited. The long-term follow-up remains to be evaluated
      with the increased number of patients treated.

PMID- 23123095
TI  - An expanding range of targets for kynurenine metabolites of tryptophan.
AB  - The kynurenine pathway of tryptophan metabolism accounts for most of the
      tryptophan that is not committed to protein synthesis and includes compounds
      active in the nervous and immune systems. Kynurenine acts on the aryl hydrocarbon
      receptor, affecting the metabolism of xenobiotics and promoting carcinogenesis.
      Quinolinic acid is an agonist at N-methyl-D-aspartate receptors (NMDARs), but is
      also pro-oxidant, has immunomodulatory actions, and promotes the formation of
      hyperphosphorylated tau proteins. Kynurenic acid blocks NMDARs and alpha7
      homomeric nicotinic cholinoceptors and is also an agonist at the orphan G-protein
      coupled receptor GPR35. 3-Hydroxykynurenine and 3-hydroxyanthranilic acid have
      pronounced redox activity and regulate T cell function. Cinnabarinic acid can
      activate metabotropic glutamate receptors. This review highlights the increasing
      range of molecular targets for components of the kynurenine pathway in both the
      nervous and immune systems in relation to their relevance to disease and drug
      development.

PMID- 23123093
TI  - Timing of transcriptional quiescence during gametogenesis is controlled by global
      histone H3K4 demethylation.
AB  - Gametes are among the most highly specialized cells produced during development.
      Although gametogenesis culminates in transcriptional quiescence in plants and
      animals, regulatory mechanisms controlling this are unknown. Here, we confirm
      that gamete differentiation in the single-celled yeast Saccharomyces cerevisiae
      is accompanied by global transcriptional shutoff following the completion of
      meiosis. We show that Jhd2, a highly conserved JARID1-family histone H3K4
      demethylase, activates protein-coding gene transcription in opposition to this
      programmed transcriptional shutoff, sustaining the period of productive
      transcription during spore differentiation. Moreover, using genome-wide
      nucleosome, H3K4me, and transcript mapping experiments, we demonstrate that JHD2
      globally represses intergenic noncoding transcription during this period. The
      widespread transcriptional defects of JHD2 mutants are associated with precocious
      differentiation and the production of stress-sensitive spores, demonstrating that
      Jhd2 regulation of the global postmeiotic transcriptional program is critical for
      the production of healthy meiotic progeny.

PMID- 23123096
TI  - AFM characterization of nanobubble formation and slip condition in oxygenated and
      electrokinetically altered fluids.
AB  - Nanobubbles are gas-filled features that spontaneously form at the interface of
      hydrophobic surfaces and aqueous solutions. In this study, an atomic force
      microscope (AFM) was used to characterize the morphology of nanobubbles formed on
      hydrophobic polystyrene (PS) and octadecyltrichlorosilane (OTS) films immersed in
      DI water, saline, saline with oxygen and an electrokinetically altered saline
      solution produced with Taylor-Couette-Poiseuille flow under elevated oxygen
      pressure. AFM force spectroscopy was used to evaluate hydrodynamic and
      electrostatic forces and boundary slip condition in various fluids. The effect of
      solution, electric field and surface charge on shape, size and density of
      nanobubbles as well as slip length was quantified and the results and underlying
      mechanisms are presented in this paper.

PMID- 23123097
TI  - Survey response of oral and maxillofacial surgeons on invasive procedures in
      patients using antithrombotic medication.
AB  - The aim was to evaluate the management strategies of Dutch oral and maxillofacial
      surgeons when performing invasive dental or oral surgery in patients using oral
      antithrombotic medication (OAM). In November 2009 a survey was mailed to all 213
      members of the Dutch Society for Oral and Maxillofacial Surgery. A response rate
      of 57% was achieved with 79 surveys returned through mail and 38 surveys answered
      through the Internet. The results show that many different treatment strategies
      are advocated by Dutch oral and maxillofacial surgeons, regarding preferred
      international normalised ratio (INR) value and continuation or discontinuation of
      OAM prior to invasive dental or oral surgery. The risk of bleeding during or
      after an invasive dental procedure was overestimated. A need for a practice
      guideline on this topic was expressed by 73% of respondents.

PMID- 23123098
TI  - Influence of pharyngeal flap surgery on maxillary outgrowth in cleft patients.
AB  - The aim of this study was to investigate the influence of the pharyngeal flap
      procedure on the frequency of Le Fort I osteotomies in full-grown nonsyndromic
      cleft patients. A retrospective review of 508 full-grown cleft patients born
      between 1 January 1983 and 31 December 1992 was performed. Following data
      analysis, 140 males older than 18 years and 111 females over the age of 16 years
      were included. 69 of the 251 included cleft patients required pharyngeal flap
      surgery (27.5%). Revision flap surgery was performed in 17.4% of the cases. A
      significantly lower age at time of the initial pharyngeal flap procedure was
      found in patients requiring revision surgery (5.6 years versus 6.8 years). The
      frequency of Le Fort I osteotomies was significantly higher in the patients with
      a pharyngeal flap (19%) compared to those without (8%) (p<0.05). The results of
      this study point towards the pharyngeal flap procedure being one of the possible
      limiting factors for maxillary antero-posterior growth in cleft patients.

PMID- 23123099
TI  - EMG biofeedback effectiveness to alter muscle activity pattern and scapular
      kinematics in subjects with and without shoulder impingement.
AB  - BACKGROUND: Muscle imbalance between serratus anterior (SA), upper trapezius
      (UA), middle trapezius (MT), and lower trapezius (LT) muscles has been observed
      in subjects with subacromial impingement syndrome (SAIS). OBJECTIVE: (1) To
      investigate the effect of electromyography (EMG) biofeedback training on muscle
      balance ratios and scapular kinematics in healthy adults and subjects with SAIS.
      (2) To investigate whether the effects of EMG biofeedback on muscle balance
      ratios are different between groups. DESIGN: Twelve healthy adults and 13
      subjects with SAIS were recruited in this study. EMG was used to record the
      activity of scapular muscles. The ratios (UT/SA, UT/MT, and UT/LT) during
      exercises with/without EMG biofeedback were calculated. Scapular kinematics were
      recorded before and after exercises with/without EMG biofeedback. RESULTS: For
      the subjects with SAIS, muscle balance ratios were lower during forward flexion
      with EMG biofeedback than during exercise only (UT/SA: 70.3-45.2; UT/LT: 124.8
      94.6). Additionally, similar results were found during side-lying external
      rotation (UT/MT: 58.5-36.4). For the scapular upward rotation and tipping in both
      groups, there were no significant differences with and without EMG biofeedback.
      CONCLUSION: EMG biofeedback improved the scapular muscular balance during
      training exercises in both groups. Further clinical trials should investigate the
      long-term effects of EMG biofeedback.

PMID- 23123100
TI  - Feasibility study of detecting surface electromyograms in severely obese
      patients.
AB  - The aims of this study were to examine if surface EMG signals can be detected
      from the quadriceps femoris muscle of severely obese patients and to investigate
      if differences exist in quadriceps force and myoelectric manifestations of
      fatigue between obese patients and lean controls. Fourteen severely obese
      patients (body mass index, BMI, mean+/-SD: 44.9+/-6.3kg/m(2)) and fourteen
      healthy controls (BMI: 23.7+/-2.5kg/m(2)) were studied. The vastus medialis and
      lateralis of the dominant thigh were concurrently investigated during voluntary
      isometric contractions (10-s long at submaximal and maximal intensities and
      intermittent submaximal contractions until exhaustion) and sustained (120-s long)
      electrically elicited contractions. We found that the detection of surface EMG
      signals from the quadriceps is feasible also in severely obese subjects
      presenting increased thickness of the subcutaneous fat tissue. In addition, we
      confirmed and extended previous findings showing that the volume conductor
      properties determine the amplitude and spectral features of the detected surface
      EMG signals: the lower the subcutaneous tissue thickness, the higher the
      amplitude and mean frequency estimates. Further, we found no differences in the
      mechanical and myoelectric manifestations of fatigue during intermittent
      voluntary and sustained electrically elicited contractions between obese patients
      and lean controls.

PMID- 23123102
TI  - Physician suicide-why?

PMID- 23123101
TI  - Details on suicide among US physicians: data from the National Violent Death
      Reporting System.
AB  - OBJECTIVE: Physician suicide is an important public health problem as the rate of
      suicide is higher among physicians than the general population. Unfortunately,
      few studies have evaluated information about mental health comorbidities and
      psychosocial stressors which may contribute to physician suicide. We sought to
      evaluate these factors among physicians versus non-physician suicide victims.
      METHODS: We used data from the United States National Violent Death Reporting
      System to evaluate demographics, mental health variables, recent stressors and
      suicide methods among physician versus non-physician suicide victims in 17
      states. RESULTS: The data set included 31,636 suicide victims of whom 203 were
      identified as physicians. Multivariable logistic regression found that having a
      known mental health disorder or a job problem which contributed to the suicide
      significantly predicted being a physician. Physicians were significantly more
      likely than non-physicians to have antipsychotics, benzodiazepines and
      barbiturates present on toxicology testing but not antidepressants. CONCLUSIONS:
      Mental illness is an important comorbidity for physicians who complete a suicide
      but postmortem toxicology data shows low rates of medication treatment.
      Inadequate treatment and increased problems related to job stress may be
      potentially modifiable risk factors to reduce suicidal death among physicians.

PMID- 23123104
TI  - [Depressive symptoms in elderly women. The influence of gender].
AB  - OBJECTIVE: To examine gender differences in depressive symptoms in people over 75
      years of age in the community. METHODS: This is a descriptive cross-sectional
      study. The data was obtained from the study of frailty in Lleida (FRALLE survey).
      Depressive symptoms were measured using the Centre for Epidemiologic Studies
      Depression Scale (CES-D). Logistic regression were used to analyse the
      relationship of gender with depressive symptoms. RESULTS: The prevalence of
      depressive symptoms was 33.1%; 22.8% for men and 40.3% for women. In the total
      population, gender was statistically significant in all three models constructed.
      Thus, women have nearly double the prevalence rates for depression compared to
      men, even after adjusting for social and demographic factors and the health
      status. CONCLUSIONS: The results suggest that women have a higher risk of
      depressive symptoms than men, and the protective factors of depressive symptoms
      are higher education in women, and the presence of a partner in men.

PMID- 23123103
TI  - Skin picking disorder in university students: health correlates and gender
      differences.
AB  - OBJECTIVE: This study sought to examine the prevalence of skin picking disorder
      (SPD) in a university sample and assess associated physical and mental health
      correlates. METHODS: A 54-item anonymous, voluntary survey was distributed via
      random email generation to a sample of 6000 university students. Current
      psychological and physical status was assessed, along with academic performance.
      Positive screens for SPD were determined based upon individuals meeting full
      proposed DSM-V criteria. RESULTS: A total of 1916 participants (31.9%; mean age
      22.7 +/- 5.1; 58.1% female) responded and were included in the analysis. The
      overall prevalence of SPD was 4.2% (females=5.8%; males=2.0%). SPD was associated
      with significantly higher lifetime rates of affective, anxiety, eating, substance
      use and impulse control disorders. Men with SPD had significantly higher BMI
      ratings and perceived themselves as significantly less attractive to others while
      women had significantly higher depressive symptoms. CONCLUSION: SPD is common in
      both genders and is associated with significant mental and physical health
      detriments, including higher levels of stress, more psychiatric comorbidity and
      poorer perceived health. Academic institutions, clinicians and public health
      officials should be aware of the multimodal presentation of SPD and screen for it
      in primary care and dermatologic settings.

PMID- 23123105
TI  - Long-term follow-up of patients with hypereosinophilic syndrome treated with
      Alemtuzumab, an anti-CD52 antibody.
AB  - BACKGROUND: Relapsing, refractory patients with idiopathic hypereosinophilic
      syndrome (I-HES) and chronic eosinophilic leukemia-not otherwise specified (CEL
      NOS) do not have many effective, durable therapeutic options. Alemtuzumab, an
      anti-CD52 antibody, has been reported to be an effective therapy due to inherent
      expression of CD52 on eosinophils. METHODS: A retrospective chart review of 12
      patients treated with alemtuzumab at our center until 2012. RESULTS: Ten (83%) of
      12 patients achieved complete hematologic response (CHR) after a median of 1 week
      for a median duration of 66 weeks, with the elimination of disease-related
      symptoms; 2 patients achieved partial hematologic remission hematologic remission
      (PHR). Patients with CHR who received alemtuzumab maintenance (n = 5) had a
      significantly longer time to progression than those patients who were only
      observed (n = 5) (P = .01). Eleven patients relapsed (only one while on
      maintenance), and 6 were rechallenged with alemtuzumab. Five (83%) achieved
      second CHR after a median of 3.5 weeks, for a median duration of 123 weeks.
      Again, those given maintenance (n = 3) had a longer time to progression than
      those who were only observed (P = .04). Adverse effects were mostly related to
      infusion reactions and lymphopenia-related viral infections (despite antibiotic
      prophylaxis). One patient developed Epstein-Barr virus-related lymphoma.
      CONCLUSIONS: Alemtuzumab is an effective treatment for patients with relapsed,
      refractory idiopathic hypereosinophilic syndrome and chronic eosinophilic
      leukemia-not otherwise specified, in terms of both CHR achievement (even after
      repeated rechallenges) and duration (particularly if provided as a maintenance
      therapy). Common adverse effects are related to infusion reactions and
      immunosuppression.

PMID- 23123107
TI  - Assessment of functional antibacterial opsonophagocytic antibodies elicited by 13
      valent pneumococcal conjugate vaccine administered concomitantly with trivalent
      influenza vaccine in a randomized clinical trial in adults aged >=65 years.
AB  - A randomized, double-blind clinical trial compared immune responses elicited by
      concomitant administration of 13-valent pneumococcal conjugate vaccine (PCV13)
      and trivalent inactivated influenza vaccine (PCV13+TIV), with PCV13 given 1 month
      after TIV, in healthy, pneumococcal vaccine-naive adults aged >=65 years.
      Serotype-specific pneumococcal anti-polysaccharide IgG antibody concentrations 1
      month post-vaccination were uniformly lower after PCV13+TIV, than after PCV13
      alone (Vaccine 2011;29:5195-202). Therefore, post hoc analyses to evaluate the
      functional antibody titers at 1-month post-vaccination, as measured by
      opsonophagocytic activity (OPA) assays, were performed. The anti-pneumococcal
      functional responses, while also generally lower after vaccine co-administration,
      nonetheless showed a greater degree of similarity between the two vaccine groups
      than was apparent from the anti-polysaccharide antibody responses. In particular,
      the proportion of OPA responders after PCV13 and TIV co-administration was
      similar to that observed after PCV13 alone for all serotypes evaluated.
      Concomitant use of PCV13 and TIV should therefore be guided by clinical
      circumstances.

PMID- 23123106
TI  - Safety and immunogenicity of pneumococcal protein vaccine candidates: monovalent
      choline-binding protein A (PcpA) vaccine and bivalent PcpA-pneumococcal histidine
      triad protein D vaccine.
AB  - BACKGROUND: Pneumococcal vaccines based on protein antigens may provide expanded
      protection against Streptococcus pneumoniae. OBJECTIVE: To evaluate safety and
      immunogenicity in adults of pneumococcal vaccine candidates comprising S.
      pneumoniae pneumococcal histidine triad protein D (PhtD) and pneumococcal choline
      binding protein A (PcpA) in monovalent and bivalent formulations. METHODS: This
      was a phase I, randomized, observer-blinded, placebo-controlled, step-wise dose
      escalation study. Following a pilot safety study in which participants received
      one intramuscular injection of either aluminum hydroxide (AH)-adjuvanted PcpA (25
      MUg) or PhtD-PcpA (10 MUg each), participants in the main study received AH
      adjuvanted PcpA (25 MUg), AH-adjuvanted PhtD-PcpA (10, 25, or 50 MUg each),
      unadjuvanted PhtD-PcpA (25 MUg each), or placebo as 2 injections 30 days apart.
      Assignment of successive dose cohorts was made after blinded safety reviews after
      each dose level. Safety endpoints included rates of solicited injection site and
      systemic reactions, unsolicited adverse events (AEs), serious AEs (SAEs), and
      safety laboratory tests. Immunogenicity endpoints included levels of anti-PhtD
      and anti-PcpA antibodies (ELISA). RESULTS: Six adults 18-50 years of age were
      included in the pilot study and 125 in the main study. No obvious increases in
      solicited reactions or unsolicited AEs were reported with escalating doses
      (adjuvanted vaccine) after either injection, or with repeated administration.
      Adjuvanted vaccine candidates were associated with a higher incidence of
      solicited reactions (particularly injection site reactions) than unadjuvanted
      vaccine candidates. However, no SAE or discontinuation due to an AE occurred.
      Geometric mean concentrations of anti-PhtD IgG and anti-PcpA IgG increased
      significantly after injection 2 compared with injection 1 at each dose level. No
      enhancement of immune responses was shown with adjuvanted vaccine candidates
      compared with the unadjuvanted vaccine candidate. In the dose-escalating
      comparison, a plateau effect at the 25 MUg dose was observed as measured by
      geometric mean concentrations and by fold increases. CONCLUSIONS: Promising
      safety profiles and immunogenicity of these monovalent and bivalent protein
      vaccine candidates were demonstrated in an adult population (ClinicalTrials.gov
      registry no. NCT01444339).

PMID- 23123108
TI  - [Urinary tract infection in infants (376 cases) in a Moroccan hospital (2009
      2010)--etiologic frequency and prevalence of resistance].

PMID- 23123109
TI  - [The irido-corneo-endothelial syndrome. The loss of the control of corneal
      endothelial cell cycle. A review].
AB  - The three major symptoms of the irido-corneo-endothelial syndrome are the
      alterations of the corneal endothelium and of the iris with a loss of the
      regulation of the cell cycle, and the progressive obstruction of the irido
      corneal angle. This rare pathology attacks mainly young adult women. Most of the
      symptoms and complications originate from the excessive proliferation of the
      corneal endothelial cells accompanied by the evolution of their phenotype towards
      that of the epithelial cells. In normal conditions the corneal endothelial cells
      do not divide, they are blocked in the G1 stage of the cell cycle, mainly because
      of the action of the inhibitors of cyclin-dependent kinases. Still these cells
      retain a good capacity for proliferation, which can be induced by the down
      regulation of the expression of the inhibitors of the cyclin-dependent kinases.
      This proliferative capacity declines with age and is also different according to
      the localization of the cells: it is more intense with those originating from the
      central area then in those from the peripheral area of the cornea. The age
      related decline of the proliferative capacity is not due to the shortening of the
      telomers, but to the stress-induced accelerated senescence of the cells.

PMID- 23123110
TI  - Promiscuous interactions of gp78 E3 ligase CUE domain with polyubiquitin chains.
AB  - Recognition of ubiquitin and polyubiquitin chains by ubiquitin-binding domains
      (UBDs) is vital for ubiquitin-mediated signaling pathways. The endoplasmic
      reticulum resident RING finger ubiquitin ligase (E3) gp78 regulates critical
      proteins via the ubiquitin-proteasome system to maintain cellular homeostasis and
      includes a UBD known as the CUE domain, which is essential for function. A
      probable role of this domain is to recognize ubiquitin-modified substrates,
      enabling gp78 to assemble polyubiquitin chains on these substrates and mark them
      for degradation. Here, we report the molecular details of the interaction of
      gp78CUE domain with ubiquitin and diubiquitin. The gp78CUE domain exhibits a well
      defined set of interactions with ubiquitin and a dynamic, promiscuous interaction
      with diubiquitin chains. This leads to a model in which the CUE domain functions
      to both facilitate substrate binding and enable switching between adjacent
      ubiquitin molecules of a growing chain to enable processivity in ubiquitination.

PMID- 23123111
TI  - Crystal structures of the HypCD complex and the HypCDE ternary complex: transient
      intermediate complexes during [NiFe] hydrogenase maturation.
AB  - [NiFe] hydrogenase maturation represents one of the most dynamic and
      sophisticated processes in metallocenter assembly. The Fe(CN)(2)CO moiety of
      [NiFe] hydrogenases is assembled via unknown transient interactions among
      specific maturation proteins HypC (metallochaperone), HypD (redox protein), and
      HypE (cyanide synthesis/donor). Here, we report the structures of the HypC-HypD
      and HypC-HypD-HypE complexes, providing a view of the transient interactions that
      take place during the maturation process. HypC binds to the conserved region of
      HypD through extensive hydrophobic interactions. The ternary complex formation
      between HypE and the HypCD complex involves both HypC and HypD, rendering the
      HypE conformation favorable for cyanide transfer. In the complex, the conserved
      cysteines of HypC and HypD form an Fe binding site. The conserved C-terminal
      cysteine of HypE can access the thiol redox cascade of HypD. These results
      provide structural insights into the Fe atom cyanation in the HypCDE complex.

PMID- 23123112
TI  - Ego3 functions as a homodimer to mediate the interaction between Gtr1-Gtr2 and
      Ego1 in the ego complex to activate TORC1.
AB  - The yeast EGO complex, consisting of Gtr1, Gtr2, Ego1, and Ego3, localizes to the
      endosomal and vacuolar membranes and plays a pivotal role in cell growth and
      autophagy regulation through relaying amino acid signals to activate TORC1. Here,
      we report the crystal structures of a wild-type and a mutant form of
      Saccharomyces cerevisiae Ego3. Ego3 assumes a homodimeric structure similar to
      that of the mammalian MP1-p14 heterodimer and the C-terminal domains of the yeast
      Gtr1-Gtr2 heterodimer, both of which function in TORC1 signaling. Structural and
      genetic data demonstrate that the unique dimer conformation of Ego3 is essential
      for the integrity and function of the EGO complex. Structural and functional data
      also identify a potential binding site for Gtr1-Gtr2. These results suggest a
      structural conservation of the protein components involved in amino acid
      signaling to TORC1 and reveal structural insights into the molecular mechanism of
      Ego3 function in TORC1 signaling.

PMID- 23123113
TI  - Occupational exposure to gases, polycyclic aromatic hydrocarbons and volatile
      organic compounds in biomass-fired power plants.
AB  - The combustion of fuels produces air pollutants in the form of gases, organic
      compounds, and particulate matter. However, although the environmental aspect of
      these agents has been examined, workers' exposure to them is still a neglected
      issue. The purpose of this study was to measure maintenance and ash removal
      workers' multiple exposures to gases, volatile organic compounds (VOCs) and
      polycyclic aromatic hydrocarbons (PAHs) during their work tasks in biomass-fired
      power plants. Our hygienic measurements revealed that carbon monoxide, nitric
      oxide, ammonia and sulfur dioxide were the most common gases that the workers
      were exposed to during their tasks. Their average concentrations were 0.45 ppm,
      0.06 ppm, 0.11 ppm and 0.42 ppm, respectively. Phenanthrene and naphthalene were
      the most prominent PAHs. At the same sampling points, the most commonly found
      VOCs were aromatic and aliphatic hydrocarbons and turpentines. The calculated
      total PAH concentrations were less than 7% of benzo[a]pyrene's eight-hour
      occupational exposure limit, and the total VOC concentrations were below the
      Finnish reference value for the normal industrial level in all measured work
      tasks. The most evident health effect caused by multiple exposures to gases was
      upper respiratory track irritation, followed by the disruption of oxygen
      transport, and finally central nervous system disorders. We recommend powered air
      respirators with ABEK+P3 cartridges and carbon monoxide gas detectors as the
      minimum requirement for those working inside biomass-fired power plant boilers,
      and compressed air breathing apparatus as the best form of protection.

PMID- 23123114
TI  - An approach for assessing potential sediment-bound contaminant threats near the
      intake of a drinking water treatment plant.
AB  - To assist in assessing a potential contaminated sediment threat near a drinking
      water intake in a large lake, a technique known as the fingerprint analysis of
      leachate contaminants (FALCON), was investigated and enhanced to help draw more
      statistically significant definitive conclusions. This represents the first
      application of this approach, originally developed by the USEPA to characterize
      and track leachate penetration in groundwater and contaminant migration from
      waste and landfill sites, in a large lake from the point-of-view of source water
      protection. FALCON provided valuable information regarding contaminated sediment
      characterization, source attribution, and transport within a surface water
      context without the need for knowledge of local hydrodynamic conditions,
      potentially reducing reliance on complicated hydrodynamic analysis. A t-test to
      evaluate the significance of correlations was shown to further enhance the FALCON
      procedure. In this study, the sensitivity of FALCON was found to be improved by
      using concentration data from both conserved organics and heavy metals in
      combination. Furthermore, data analysis indicated that it may be possible to
      indirectly assess the success of remediation efforts (and the corresponding need
      to plan for a treatment upgrade in the event of escalating contaminant
      concentrations) by examining the temporal change in correlation between the
      source and intake sediment fingerprints over time. This method has potential for
      widespread application in situations where conserved contaminants such as heavy
      metals and higher molecular weight polycyclic aromatic hydrocarbons (PAHs), are
      being or have previously been deposited in sediment somewhere in, or within range
      of, an intake protection zone.

PMID- 23123115
TI  - Polychlorinated biphenyl spatial patterns in San Francisco Bay forage fish.
AB  - Industrialized waterways frequently contain nearshore hotspots of legacy
      polychlorinated biphenyl (PCB) contamination, with uncertain contribution to
      aquatic food web contamination. We evaluated the utility of estuarine forage fish
      as biosentinel indicators of local PCB contamination across multiple nearshore
      sites in San Francisco Bay. Topsmelt (Atherinops affinis) or Mississippi
      silverside (Menidia audens) contamination was compared between 12 targeted sites
      near historically polluted locations and 17 probabilistically chosen sites
      representative of ambient conditions. The average sum of 209 PCB congeners in
      fish from targeted stations (441+/-432 ng g(-1) wet weight, mean+/-SD) was
      significantly higher than probabilistic stations (138+/-94 ng g(-1)).
      Concentrations in both species were comparable to those of high lipid sport fish
      in the Bay, strongly correlated with spatial patterns in sediment contamination,
      and above selected literature thresholds for potential hazard to fish and
      wildlife. The highest concentrations were from targeted Central Bay locations,
      including Hunter's Point Naval Shipyard (1347 ng g(-1); topsmelt) and Stege Marsh
      (1337 ng g(-1); silverside). Targeted sites exhibited increased abundance of
      lower chlorinated congeners, suggesting local source contributions, including
      Aroclor 1248. These findings indicate that current spatial patterns in PCB
      bioaccumulation correlate with historical sediment contamination due to
      industrial activity. They also demonstrate the utility of naturally occurring
      forage fish as biosentinels of localized PCB exposure.

PMID- 23123116
TI  - Potential mobility of heavy metals through coupled application of sequential
      extraction and isotopic exchange: comparison of leaching tests applied to soil
      and soakaway sediment.
AB  - Artificial infiltration facilities (AIFs) that enhance groundwater recharge and
      regulate urban runoff are going to be an integral element of the urban
      infrastructure. However, AIFs provide a sink which trap pollutants that are
      likely to cause groundwater contamination. The current study aimed first to
      examine the mobility characteristics of Cu, Zn, and Pb through soil and soakaway
      sediment using an integrated analytical approach for column leaching with
      artificial road runoff (ARR) and then to differentiate the sorption patterns
      among different samples, (i.e., surface soil, underlying soil, and soakaway
      sediments) using mass balances. In addition, the study compares metal retention
      and release under continuous and intermittent flow conditions. Column leaching
      experiments were conducted using batches for 10 and 30 d under continuous flow
      condition and for 20 d of intermittent leaching. Heavy metal content and
      partitioning in soil and sediment used in columns were well characterized before
      and after leaching experiments. The results showed that a gradual increase in pH
      and decrease in dissolved organic carbon had pronounced effect on the
      mobilization of heavy metals. Pb showed the highest retention compared to Cu and
      Zn which implies that metal complexes play a pivotal role in metal transport.
      Labile fractions were found to be trapped by the solid materials for retention
      and their high concentration in ARR is a major concern from the pollution point
      of view through infiltration facilities. Results obtained in this study predict
      the risk associated with the release of retained heavy metal under changing
      environmental conditions in AIFs.

PMID- 23123117
TI  - Amino acid neurotoxins in feathers of the Lesser Flamingo, Phoeniconaias minor.
AB  - The Lesser Flamingo (Phoeniconaias minor) is known to use cyanobacteria
      (primarily Arthrospira) as a major food source in the East African Rift Valley
      lakes. Periodically, mass mortalities have occurred, associated with the
      cyanobacterial toxins (cyanotoxins), microcystins and anatoxin-a. Deposition of
      these cyanotoxins into P. minor feathers has been shown to occur, consistent with
      the presence of cyanotoxins in the livers, stomach and faecal contents after
      dietary intake. As cyanobacteria have been shown to also produce the neurotoxins
      beta-N-methylamino-L-alanine (BMAA) and 2,4-diaminobutyric acid (DAB), stored
      wing feathers, previously recovered from flamingos which had been exposed to
      microcystins and anatoxin-a and had subsequently died, were analysed for these
      neurotoxic amino acids. Trace amounts of BMAA were detected in extracts from Lake
      Nakuru flamingo feathers, with DAB also present at concentrations between 3.5 and
      8.5 MUg g(-1) dry weight in feathers from both lakes. Toxin recovery by solid
      phase extraction of feather digests was tested with spiked deuterated BMAA and
      showed good recovery when analysed by LC-MS/MS (80-94%). This is the first report
      of these neurotoxic amino acids in birds. We discuss the origin and significance
      of DAB, alongside other cyanotoxins of dietary origin, in the feathers of the
      Lesser Flamingo.

PMID- 23123118
TI  - Winter peaks of methylmercury in deposition to a remote Scottish mountain lake.
AB  - Depositional records of methylmercury (MeHg) are rare, especially for remote and
      mountainous areas. Our data from Lochnagar, a mountain lake in Scotland, covering
      a 7-year period from 2001-2008, show an unusual seasonal pattern in that elevated
      MeHg concentrations occur each winter while concentrations each summer fall below
      the limit of detection. To our knowledge this is the first time this seasonal
      pattern has been reported. Peak concentrations at the site in October 2006 (1.2
      ng L(-1)) are amongst the highest reported depositional values in the literature.
      As the soils and lakes in the region are frozen or snow covered for much of each
      winter, we consider possible sources of this winter deposited MeHg to be either
      aqueous phase methylation in the atmosphere or marine evasion. However, the
      factor driving this seasonal pattern is likely to be scavenging by snow, as
      elevated concentrations in deposition coincide with periods of snowfall at the
      site. If this mechanism is correct, then predicted impacts of climate change,
      which will reduce annual snowfall at the site by between 50% and 100% by 2080,
      will effectively eliminate this input source. However, other climate-influenced
      inputs of mercury, such as remobilisation from catchment soils, are likely to
      increase and negate any benefit.

PMID- 23123119
TI  - Effects of bisphenol A on growth, photosynthesis and chlorophyll fluorescence in
      above-ground organs of soybean seedlings.
AB  - Bisphenol A (BPA) is a representatively endocrine disruptor, which shows a highly
      toxic effect on life system. Its potential toxicity on plants that are the
      primary producers in earth's ecosystem is not well documented. Here, the effects
      of BPA on the growth, photosynthesis, content of chlorophyll (Chl), initial
      fluorescence (F(0)), maximal photochemical efficiency (F(v)/F(m)), effective
      quantum yield of photosystem II (Phi(PSII)) and photosynthetic electron transport
      rate (ETR) in soybean seedlings were investigated by using gas exchange
      measurement system and chlorophyll fluorometer to understand the toxic effect of
      BPA on plants. It was found that when soybean seedlings were treated with BPA at
      the low concentration (1.5 mg L(-1)), the growth indices (the plant height, fresh
      and dry weights of stems, fresh and dry weights of leaves, leaf area) were
      increased obviously compared with those of the control, which was not related
      with the photosynthesis, the content of Chl and the chlorophyll fluorescence.
      When soybean seedlings were treated with BPA at the high concentrations (7.0,
      12.0, 17.2 and 50.0 mg L(-1)), the growth indices, net photosynthetic rate, the
      content of chlorophyll, F(v)/F(m), Phi(PSII), ETR were decreased, while F(0) was
      increased, compared with those of the control. Obviously, BPA at the high
      concentrations showed the toxic effect on soybean seedlings. The results from
      correlation analysis indicated that the inhibition in the growth of soybean
      seedlings treated with BPA was related to the decrease in photosynthesis because
      of the decrease in the content of chlorophyll and the change in chlorophyll
      fluorescence.

PMID- 23123120
TI  - Photo-induced self-cleaning and sterilizing activity of Sm3+ doped ZnO
      nanomaterials.
AB  - Highly active samarium doped zinc oxide self-cleaning and biocidal surfaces (x
      mol% Sm(3+)/ZnO where x=0, 1, 2 and 4 mol%) with crystalline porous structures
      were synthesized by hydrothermal method. Sm(3+)/ZnO thin films were characterized
      by X-ray diffraction (XRD), transmission electron microscope (TEM), scanning
      electron microscope (SEM), energy dispersive spectroscopic (EDS), UV-visible
      diffuse reflectance and fluorescence (FL) spectroscopy. The combination between
      doping and hydrothermal treatments significantly altered the morphology of ZnO
      into rod and plate-like nanoshapes structure and enhanced its absorption and
      emission of ultraviolet radiation. The photo-activity in term of quantitative
      determination of the active oxidative species (()OH) produced on the thin film
      surfaces was evaluated using fluorescent probe method. The results showed that,
      the hydrothermally treated 2.0 mol% Sm(3+)/ZnO film (S2) is the highly active
      one. The optical, structural, morphology and photo-activity properties of the
      highly active thin film (S2) make it promising surface for self-cleaning and
      sterilizing applications.

PMID- 23123121
TI  - Reverse transcription-loop-mediated isothermal amplification for the detection of
      rodent coronaviruses.
AB  - Mouse hepatitis virus (MHV) is one of the most prevalent viruses detected in
      laboratory mouse colonies. Enterotropic strains predominate in natural
      infections, and molecular techniques for the detection of MHV shedding in feces
      are powerful enough to diagnose active infections. A reverse transcription-loop
      mediated isothermal amplification (RT-LAMP) technique was developed for the
      detection of rodent coronaviruses within 90 min. The specificity of this
      technique was confirmed by its ability to detect all 17 different strains of MHV
      and 6 strains of rat coronaviruses as well as its failure to detect human,
      bovine, and porcine coronaviruses nonspecifically. The sensitivity of RT-LAMP was
      3.2-fold higher than that of reverse transcription-polymerase chain reaction (RT
      PCR) and 31.6-fold lower than that of nested RT-PCR. An evaluation of the
      diagnostic performance of RT-LAMP performed in duplicate using mouse fecal
      specimens showed that the sensitivity and specificity with respect to nested RT
      PCR were 85.7% and 100%, respectively. RT-LAMP assays would be suitable for
      monitoring active MHV infection in mouse colonies.

PMID- 23123122
TI  - Identification of three H-2K(d) restricted CTL epitopes of NS4A and NS4B protein
      from Yellow fever 17D vaccine.
AB  - In this study, 12 nonamers derived from the nonstructural protein NS4A and NS4B
      of a Chinese attenuated Yellow fever 17D (YF-17D) vaccine strain were screened
      for their ability to elicit a recall interferon-gamma (IFN-gamma) response from
      the splenocytes of BALB/c mice following DNA vaccination and a booster
      vaccination with recombinant vaccinia virus expressing NS4A or NS4B protein.
      Three peptides (amino acid residues S(106)YIMLIFFV from NS4A protein and
      V(43)YVGIVTML and L(174)YLLLALSL from NS4B protein) were identified as CD8(+)
      cytotoxic T lymphocyte (CTL) epitopes. These peptides elicited a response from a
      significant numbers of IFN-gamma secreting cells compared with the other nonamers
      of NS4A and NS4B and compared to one irrelevant nonamer derived from infectious
      bronchitis virus (IBV) H52 strain. Bioinformatics analysis demonstrated that
      these three nonamers are H-2K(d)-restricted CTL epitopes. The multiple amino acid
      sequence alignments among different YFV NS4A, and NS4B sequences submitted to
      GenBank indicated that these three CTL epitopes are strongly conserved; this
      novel finding will potentially aid further studies on cellular immunity against
      YF virus and YFV-based expression vectors.

PMID- 23123124
TI  - Pathological features of systemic necrotizing vasculitis (polyarteritis nodosa)
      in sheep.
AB  - Polyarteritis nodosa (PAN) is a systemic vasculitis of unknown aetiology
      affecting small- and medium-sized arteries of multiple organ systems without
      involvement of pulmonary arteries. This report describes four cases of PAN in
      sheep from different flocks. Three of these animals displayed clinical signs of
      locomotor disturbance. Gross necropsy findings included bilateral nodular
      thickening of vessels together with thromboses and aneurysms at several
      locations. Microscopically, small- to medium-sized arteries of the kidneys,
      ovary, uterus and skin were consistently involved and other locations were
      affected less frequently. Arteries within the lung were normal in all animals.
      Vascular lesions were characterized by focal fibrinoid necrosis, rupture of the
      internal elastic lamina and transmural infiltration of mononuclear inflammatory
      cells, extending into the perivascular tissue. In the kidney, many arteries
      showed narrowing or occlusion of the lumen and marked fibrosis. The distribution
      of arterial lesions was segmental, showing alternation of affected and
      microscopically normal areas. Immunohistochemical studies did not identify immune
      complex deposition. The inflammatory infiltrates were composed of T lymphocytes
      and macrophages, suggesting that a cell-mediated immune response may be involved
      in the pathogenesis of this disease.

PMID- 23123123
TI  - Dystrophic epidermolysis bullosa in goats.
AB  - Clinical, histopathological and ultrastructural findings of caprine dystrophic
      epidermolysis bullosa (DEB) with autosomal recessive inheritance are reported.
      The goats presented with exungulation, erosions, crusts and scars on the skin and
      ulcers in the oral cavity. Microscopically, the skin showed subepidermal
      separation with clefts filled occasionally with clear eosinophilic fluid,
      cellular debris or neutrophils. Ultrastructurally, the site of blister formation
      was the sublamina densa in the epidermal basement membrane zone. In skin with
      blister formation and in clinically uninvolved skin, the basal lamina was
      preserved, but the anchoring fibrils were sparse and rudimentary. A twin brother
      of an affected kid was mated over 5 years with his mother; three out of the 10
      kids born presented with epidermolysis bullosa, indicating that the disease has
      an autosomal recessive mode of inheritance. It is suggested that the disease is
      similar to human severe generalized recessive DEB.

PMID- 23123125
TI  - Differential regulation of GnRH ligand and receptor genes in the brain and
      pituitary of Atlantic cod exposed to different photoperiod.
AB  - The onset of puberty and reproduction are tightly controlled by extrinsic and
      intrinsic inputs combined with genetically determined biological blueprints.
      Environmental inputs are then mediated by the brain-pituitary-gonad endocrine
      axis resulting in a unified output. In fish, one of the primary factors
      controlling the timing of sexual maturation is light, although how these signals
      are mediated in the brain and pituitary is not well understood. We therefore
      aimed to elucidate the molecular basis of the control of reproduction during the
      first spawning season in two year old female Atlantic cod. To this end, we
      measured GnRH and GnRH-R variant gene expression in brains and pituitaries
      collected from cod kept under four different photoperiod regimes: natural light
      (NL), continuous light (LL) and combined treatment of NL-LL and LL-NL. LL
      inhibited sexual development and spawning and LL-NL delayed sexual development
      and spawning. LL inhibited the spawning-related increase in brain GnRH3 and
      pituitary GnRH-R2a gene expression found under NL conditions, and the expression
      of these genes were delayed in concert with spawning of LL-NL cod. This study
      indicates that regulation of brain GnRH3 and pituitary GnRH-R2a genes likely
      mediates photoperiod induced changes in cod gonadal maturation.

PMID- 23123126
TI  - Unexplained extreme hyperbilirubinemia among neonates in a multihospital
      healthcare system.
AB  - We report a series of neonates who developed a total serum bilirubin (TSB)
      >20mg/dL during a recent ten-year period in a multihospital healthcare system.
      The incidence of a TSB >20mg/dL fell after instituting a pre-hospital discharge
      bilirubin screening program in 2003/2004 (91.3 cases/10,000 births before vs.
      72.4/10,000 after), but the incidence has subsequently remained unchanged. No
      specific cause for the hyperbilirubinemia was identified in 66% of (n=32) cases
      with a TSB >30 mg/dL or in 76% of (n=112) cases with a TSB 25.0-29.9 mg/dL. We
      hypothesized that hemolysis was a common contributing mechanism, but our review
      of hospital records indicated that in most instances these infants were not
      evaluated sufficiently to test this hypothesis. Records review showed maternal
      and neonatal blood types and direct antiglobulin testing were performed in >95%
      cases, but rarely were other tests for hemolysis obtained. In the ten-year period
      reviewed there were zero instances where erythrocyte morphology from a blood film
      examination or Heinz body evaluation by a pediatric hematologist or pathologist
      were performed. In 3% of cases pyruvate kinase was tested, 3% were evaluated by
      hemoglobin electrophoresis, 3% had a haptoglobin measurement, and 16% were tested
      for G6PD deficiency. Thus, determining the cause for hyperbilirubinemia in
      neonates remains a problem at Intermountain Healthcare and, we submit, elsewhere.
      As a result, the majority of infants with a TSB >25mg/dL have no specific
      causation identified. We speculate that most of these cases involve hemolysis and
      that the etiology could be identified if searched for more systematically. With
      this in mind, we propose a "consistent approach" to evaluating the cause(s) of
      hyperbilirubinemia among neonates with a TSB >25mg/dL.

PMID- 23123127
TI  - Evaluation of immunohistochemical markers of lymphatic and blood vessels in
      canine mammary tumours.
AB  - Canine mammary tumours (CMTs) are the most common neoplasms in intact female
      dogs. Bitches with spontaneously arising CMTs represent a promising animal model
      for human breast cancer research. The aim of the present study was to develop an
      immunohistochemical protocol for the identification of blood and lymphatic
      vessels in CMTs. Antibodies specific for human lymphatic vessels (prox-1, lyve-1,
      podoplanin and D2-40) and blood vessels (von Willebrand factor [vWf], CD31 and
      CD34) were utilized. Serial sections of 18 samples (eight samples of normal
      canine mammary tissue, five benign and five malignant CMTs) were examined.
      Antibodies specific for podoplanin, D2-40 and CD34 showed no immunoreactivity
      with canine tissue. Prox-1 and CD31 were determined to be the most suitable
      markers for lymphatic and blood vessels, respectively.

PMID- 23123128
TI  - Severe subacute necrotizing encephalopathy (Leigh-like syndrome) in American
      Staffordshire bull terrier dogs.
AB  - Seventeen American Staffordshire bull terrier puppies, 6-8 weeks of age, from
      seven closely related litters, presented with rapidly progressive central
      vestibular neurological signs. Previously reported hereditary ataxias in the
      breed, including l-2 hydroxyglutaric aciduria and cerebellar cortical
      degeneration, as well as thiamine deficiency, were excluded. Elevated lactate
      levels and lactate:pyruvate ratios gave supporting evidence of a defect of the
      respiratory chain or Leigh-like syndrome. Histopathology in all cases showed a
      bilaterally symmetrical necrotizing encephalopathy, with malacia of the neuropil
      centred on the vestibular and olivary nuclei of the brainstem. This is the first
      documentation of a heritable rapidly progressive lethal necrotizing
      encephalopathy consistent with Leigh-like syndrome, in American Staffordshire
      bull terrier dogs.

PMID- 23123129
TI  - Adrenal cortex carcinomas with distant metastases in beef cattle at slaughter.
AB  - Ten cases of adrenal cortex carcinomas with distant metastases were collected as
      subclinical lesions at slaughter of approximately 14,000 adult cattle. The
      primary lesion in the adrenal gland and the distant metastases, to either the
      lung or liver, were characterized by light microscopy and immunohistochemistry.
      Carcinomas were usually detected by noting metastases in the lungs as polypoid,
      soft, red or red and yellow masses. All adrenal tumours were unilateral and none
      were seen in bulls. In six of 10 carcinomas there was gross evidence of invasion
      of the vena cava via the adrenal vein. Normal bovine adrenal cortex labelled
      positively with S100, calretinin, alpha inhibin and melan-A; however, adenomas
      and seven of 10 carcinomas were labelled best by melan-A and alpha inhibin. Three
      carcinomas, grossly identical to the other seven, had numerous calcific granules
      and a slightly different microscopical appearance. In addition to melan-A and
      alpha-inhibin, these variant carcinomas labelled with S100. This variant may be
      derived from a different layer of the adrenal cortex. Because of the similarity
      of the bovine and human adrenal cortices, cultures of spontaneously arising
      bovine adrenal tumours may be a useful resource for study of human neoplasia.

PMID- 23123130
TI  - Experiences in Ethiopia: a report of a visit supported by the Journal of
      Comparative Pathology Educational Trust.

PMID- 23123131
TI  - Otitis media associated with Cryptosporidium baileyi in a Saker falcon (Falco
      cherrug).
AB  - A 7-week-old male Saker falcon died with a history of severe refractory dyspnoea
      and respiratory signs. Microscopical lesions included moderate to severe
      lymphoplasmacytic inflammation of the middle ears, conjunctivae, third eyelids,
      choanae, salivary glands of the tongue, turbinates, larynx, trachea, syrinx and
      bronchi. The lesions were associated with variable numbers of Cryptosporidium
      spp., further confirmed by transmission electron microscopy and in-situ
      hybridization. Cryptosporidium baileyi was identified by DNA sequence analysis.
      C. baileyi may therefore be a cause of otitis media in raptors as it is in man.
      It is most likely that the middle ears of the Saker falcon acquired the infection
      through the eustachian tubes that originate near the pharynx in the oral cavity.
      This is the first description of otitis media associated with C. baileyi in a
      bird or a mammal except man.

PMID- 23123132
TI  - Aggression in bipolar II disorder and its relation to the serotonin transporter.
AB  - BACKGROUND: Aggression is frequently observed in patients diagnosed with bipolar
      disorder (BD). Previous studies found a negative association between aggression
      and serotoninergic function in patients with BD, as well as in healthy subjects.
      The objective of this study was to determine whether there is an association
      between aggression and the availability of the serotonin transporter (SERT) in
      euthymic BD II patients. METHODS: Thirty-eight age-matched healthy controls (HCs)
      and 24 BD II patients were recruited. BD II patients were under stable treatment
      in the euthymic state. The Overt Aggression Scale (OAS) was used for the
      assessment of aggression. Single photon emission computed tomography with (123)I
      ADAM was used for SERT imaging. A specific uptake ratio, which represents
      availability, was the primary measured outcome. RESULTS: The total OAS scores, as
      well as the scores on all of the sub-items, were significantly higher in BD II
      patients than in the HCs group. There was no significant difference in SERT
      availability between BD II and HCs subjects in different brain regions. The
      Pearson's correlation between the total OAS scores and the sub-item aggression
      and SERT availability was significant. LIMITATION: The OAS was used for the
      assessment of the past week of the patients' condition and thus did not reflect
      their trait status. CONCLUSIONS: The higher total scores of OAS in euthymic BD II
      patients than in HCs support the idea that aggression might be a trait marker for
      BD. Although SERT availability in euthymic BD II patients and in HCs did not
      differ significantly, the correlation of SERT availability and total OAS provides
      the possible explanation of aggression in BD II.

PMID- 23123133
TI  - Socio-emotional processing and functioning of youth at high risk for bipolar
      disorder.
AB  - BACKGROUND: The goal of this study was to investigate differences in socio
      emotional processing and functioning in children and adolescents at high risk for
      bipolar disorder (BD) and healthy control participants. METHODS: Children and
      adolescents with a parent with bipolar disorder, who had mood dysregulation but
      not fully syndromal BD (high risk, HR, n=24), were compared to participants with
      no personal or family history of psychopathology (healthy control, HC, n=27)
      across several neuropsychological domains. Social reciprocity was measured by the
      Social Responsiveness Scale, theory of mind was measured by use of the NEPSY, and
      affect recognition was measured by the NEPSY and the Diagnostic Test of Nonverbal
      Accuracy 2 (DANVA). RESULTS: The HR group demonstrated significant impairment in
      social reciprocity, including impairments in social awareness, social cognition,
      social communication, social motivation, and autistic mannerisms. There were no
      significant group differences in performance on theory of mind or affect
      recognition tasks. LIMITATIONS: Lack of impairment in tasks associated with
      theory of mind or affect recognition indicate that social functioning
      difficulties are not likely due to impairments in these areas, or that the
      measures employed were not sufficiently sensitive to detect group differences.
      CONCLUSIONS: Youth at high risk for BD demonstrated impairments in numerous
      social domains, which may be due to innate differences in brain development
      governing socio-emotional functioning or may be due to disruptions in normal
      development caused by mood regulation difficulties.

PMID- 23123134
TI  - Hippocampal volume in subjects at high risk of psychosis: a longitudinal MRI
      study.
AB  - INTRODUCTION: The hippocampal formation has been studied extensively in
      schizophrenic psychoses and alterations in hippocampal anatomy have been
      consistently reported. Chronic schizophrenia seems to be associated with
      bilateral hippocampal volume (HV) reduction, while in patients with an at-risk
      mental state (ARMS) there are contradictory results. This is the first region of
      interest (ROI) based follow-up MRI study of hippocampal volume comparing ARMS
      individuals with and without transition to psychosis. The aim was to investigate
      the timing of HV changes in ARMS in the early phase of psychosis. METHODS:
      Magnetic resonance imaging data from 18 antipsychotic-naive individuals with an
      ARMS were collected within the FePsy-clinic for early detection of psychoses.
      During follow-up 8 subjects transitioned to psychosis (ARMS-T) and 10 did not
      (ARMS-NT). Subjects were re-scanned after the onset of psychosis or at the end of
      the follow-up if they did not develop psychosis. RESULTS: Across both groups
      there was a significant decrease in HV over time (p<0.05). There was no
      significant difference in progression between ARMS-T and ARMS-NT. Antipsychotic
      medication at follow up was associated with increased HV (p<0.05). CONCLUSIONS:
      We found a decrease of HV over time in subjects with an ARMS, independently of
      clinical outcome. We may speculate that the decrease of HV over time might
      reflect brain degeneration processes.

PMID- 23123135
TI  - Platelet-associated tissue factor enhances platelet reactivity and thrombin
      generation in experimental studies in vitro.
AB  - INTRODUCTION: The thrombogenic potential of tissue factor (TF) associated to
      platelets is controversial. We have investigated the in vitro contribution of
      platelet-associated TF to thrombus formation. MATERIALS AND METHODS: Platelets
      suspensions were exposed to human TF-rich microvesicles (TF-MV) from placental or
      recombinant origin. Platelet-associated TF was quantified through coagulometric
      assays. Adhesive and cohesive properties of platelets containing TF were assessed
      in perfusion models using two thrombogenic surfaces: 1) type-I collagen, or 2)
      damaged vascular segments. Perfusion studies were performed with heparinized
      blood enriched with a 30% of washed platelets exposed to TF-MV vs. washed control
      platelets. Thrombin generation and thromboelastometric properties of clots were
      also assessed using a fluorometric assay and ROTEM analysis, respectively.
      Inhibitory strategies with an antibody to TF were performed in some cases.
      RESULTS: The addition of 30% of platelets containing TF to blood perfusates
      resulted in a statistically significant increase in the platelet coverage (%CS)
      vs. non-exposed platelets on collagen surfaces (%CS: 19.7 +/- 0.6 and 23.9 +/-
      0.7 respectively, vs.14.5 +/- 1.4; p<0.01) and on the vascular subendothelium
      (%CS: 54.0 +/- 1.5 and 47.2 +/- 6.8 respectively vs. 38.0 +/- 3.5, p<0.05), with
      a statistically significant increase in the size of large platelet aggregates
      (p<0.05) vs. control platelets. These effects on collagen surfaces were almost
      totally prevented by an antibody to TF. Platelet-associated TF significantly
      accelerated thrombin generation and clot formation (p<0.05), effects that were
      partially prevented by a neutralizing anti-TF. CONCLUSIONS: Platelet-associated
      TF potentiated adhesive and aggregating properties in in vitro studies with
      flowing blood and accelerated thrombin generation and clot formation time under
      steady conditions.

PMID- 23123136
TI  - Association of ankylosing spondylitis with HLA-B27 and ERAP1: pathogenic role of
      antigenic peptide.
AB  - Ankylosing spondylitis (AS) is a form of seronegative inflammatory arthritis
      whose strong genetic association with the human leucocyte antigen (HLA)-B27 has
      been known for almost 4 decades. However, its mechanism remains poorly
      understood. Recently, with the development of genetics, further more genes have
      been robustly associated with the disease. Genome-wide association studies
      identified the association between AS and ERAP1 (endoplasmic reticulum associated
      aminopeptidase 1). And ERAP1 has shown the potential in trimming antigenic
      peptides to optimal length for binding to HLA-B27 in the ER (endoplasmic
      reticulum). However, the length of the peptides are strictly restricted in the
      process of peptide transporting, processing and presentation. A hypothesis is
      proposed that the abnormal mechanism of AS may related to the trimming of N
      terminal sequences from antigenic precursors in the ER and the length of the
      antigenic peptides that are presented to the T-cell receptors.

PMID- 23123137
TI  - Epigenetic silencing of Klotho expression correlates with poor prognosis of human
      hepatocellular carcinoma.
AB  - Klotho is identified as a tumor suppressor in several tumors, but the expression
      of the Klotho gene (KL) and its regulative mechanism are not reported in
      hepatocellular carcinoma (HCC). The messenger RNA and protein levels of Klotho
      were measured in 64 HCC tumor tissues by real-time polymerase chain reaction and
      immunohistochemistry, respectively. The methylation of KL promoter DNA was
      examined by bisulfite-based polymerase chain reaction. The correlation of Klotho
      protein expression and methylation with survival of HCC was analyzed using Kaplan
      Meier analysis. The interference of KL gene expression was conducted in HCC cells
      by DNA demethylating agent and/or histone deacetylase inhibitor. In HCC tissues,
      a significant loss of Klotho messenger RNA and protein expression was observed,
      which parallels the increased methylation in KL promoter DNA. Both Klotho
      expression and methylation correlated with the poor prognosis of HCC. Experiments
      with HCC cell lines showed that a combination of DNA demethylating agent and
      histone deacetylase inhibitor fully recovered Klotho expression and subsequently
      induced cell apoptosis. In conclusion, Klotho is a tumor suppressor in HCC. Both
      hypermethylation and acetylation are involved in the loss of Klotho expression in
      HCC cells. Both KL gene expression and its promoter DNA methylation are
      predictive factors for the poor prognosis of HCC. Our study also suggests that
      the Klotho gene could be a target for therapy of HCC.

PMID- 23123138
TI  - Enhanced radiosyntheses of [11C]raclopride and [11C]DASB using ethanolic loop
      chemistry.
AB  - INTRODUCTION: To improve the synthesis and quality control of carbon-11 labeled
      radiopharmaceuticals, we report the fully automated loop syntheses of
      [11C]raclopride and [11C]DASB using ethanol as the only organic solvent for
      synthesis module cleaning, carbon-11 methylation, HPLC purification, and
      reformulation. METHODS: Ethanolic loop chemistry is fully automated using a GE
      TRACERLab FX(C-Pro) synthesis module, and is readily adaptable to any other
      carbon-11 synthesis apparatus. Precursors (1 mg) were dissolved in ethanol (100
      MUL) and loaded into the HPLC loop. [11C]MeOTf was passed through the HPLC loop
      and then the labeled products were purified by semi-preparative HPLC and
      reformulated into ethanolic saline. RESULTS: Both [11C]raclopride (3.7% RCY; >95%
      RCP; SA=20831 Ci/mmol; n=64) and [11C]DASB, both with (3.0% RCY; >95% RCP;
      SA=15152Ci/mmol; n=9) and without (3.0% RCY; >95% RCP; SA=10931 Ci/mmol; n=3)
      sodium ascorbate, have been successfully prepared using the described
      methodology. Doses are suitable for human use and the described methods are now
      employed for routine clinical production of both radiopharmaceuticals at the
      University of Michigan. CONCLUSIONS: Ethanolic loop chemistry is a powerful
      technique for preparing [11C]raclopride and [11C]DASB, and we are in the process
      of adapting it for other carbon-11 radiopharmaceuticals prepared in our
      laboratories ([11C]PMP, [11C]PBR28 etc.).

PMID- 23123139
TI  - Imaging of rat cerebral ischemia-reperfusion injury using(99m)Tc-labeled
      duramycin.
AB  - OBJECTIVES: Prompt identification of necrosis and apoptosis in the infarct core
      and penumbra region is critical in acute stroke for delineating the underlying
      ischemic/reperfusion molecular pathologic events and defining therapeutic
      alternatives. The objective of this study was to investigate the capability of
      (99m)Tc-labeled duramycin in detecting ischemia-reperfusion injury in rat brain
      after middle cerebral artery (MCA) occlusion. METHODS: Ischemic cerebral injury
      was induced in ten rats by vascular insertion of a nylon suture in the left MCA
      for 3 hr followed by 21-24hr reperfusion. After i.v. injection of (99m)Tc
      duramycin (1.0-3.5 mCi), dynamic cerebral images were acquired for 1 hr in six
      rats using a small-animal SPECT imager. Four other rats were imaged at 2 hr post
      injection. Ex vivo images were obtained by autoradiography after sacrifice.
      Histologic analyses were performed to assess cerebral infarction and apoptosis.
      RESULTS: SPECT images showed that (99m)Tc-duramycin uptake in the left cerebral
      hemisphere was significantly higher than that in the right at 1 and 2 hr post
      injection. The level of radioactive uptake in the ischemic brain varied based on
      ischemic severity. The average ratio of left cerebral hot-spot uptake to right
      hemisphere radioactivity, as determined by computerized ROI analysis, was 4.92+/
      0.79. Fractional washout at 1 hr was 38.2+/-4.5% of peak activity for left
      cerebral hot-spot areas and 80.9+/-2.0% for remote control areas (P<0.001). Based
      on triphenyltetrazolium chloride staining and autoradiograph image data, the
      hotspot uptake may be associated primarily with the ischemic penumbra, in which
      high apoptotic activity was observed by cleaved caspase-3 immunocytochemical
      staining. CONCLUSIONS: (99m)Tc-duramycin SPECT imaging may be useful for
      detecting and quantifying ongoing apoptotic neuronal cell loss induced by
      ischemia-reperfusion injury.

PMID- 23123140
TI  - The use of bioelectrical impedance analysis to estimate total body water in young
      children with cerebral palsy.
AB  - BACKGROUND & AIMS: Body composition assessment is an essential component of
      nutritional evaluation in children with cerebral palsy. This study aimed to
      validate bioelectrical impedance to estimate total body water in young children
      with cerebral palsy and determine best electrode placement in unilateral
      impairment. METHODS: 55 young children with cerebral palsy across all functional
      ability levels were included. Height/length was measured or estimated from knee
      height. Total body water was estimated using a Bodystat 1500MDD and three
      equations, and measured using the gold standard, deuterium dilution technique.
      Comparisons were made using Bland Altman analysis. RESULTS: For children with
      bilateral impairment, the Fjeld equation estimated total body water with the
      least bias (limits of agreement): 0.0 L (-1.4 L to 1.5 L); the Pencharz equation
      produced the greatest: 2.7 L (0.6 L-4.8 L). For children with unilateral
      impairment, differences between measured and estimated total body water were
      lowest on the unimpaired side using the Fjeld equation 0.1 L (-1.5 L to 1.6 L))
      and greatest for the Pencharz equation. CONCLUSIONS: The ability of bioelectrical
      impedance to estimate total body water depends on the equation chosen. The Fjeld
      equation was the most accurate for the group, however, individual results varied
      by up to 18%. A population specific equation was developed and may enhance the
      accuracy of estimates. Australian New Zealand Clinical Trials Registry (ANZCTR)
      number: ACTRN12611000616976.

PMID- 23123141
TI  - Age-related changes in the somatosensory processing of tactile stimulation--an
      fMRI study.
AB  - Age-related changes in brain function are complex. Although ageing is associated
      with a reduction in cerebral blood flow and neuronal activity, task-related
      processing is often correlated with an enlargement of the corresponding and
      additionally recruited brain areas. This supplemental employment is considered an
      attempt to compensate for deficits in the ageing brain. Although there are
      contradictory reports regarding the role of the primary somatosensory cortex
      (SI), currently, there is little knowledge about age-related functional changes
      in other brain areas in the somatosensory network (secondary somatosensory cortex
      (SII), and insular, anterior (ACC) and posterior cingulate cortices (PCC)). We
      investigated 16 elderly (age range, 62-71 years) and 18 young subjects (age
      range, 21-28 years) by determining the current perception threshold (CPT) and
      applying functional magnetic resonance imaging (fMRI) using a 3.0 Tesla scanner
      under tactile stimulation of the right hand. CPT was positively correlated with
      age. fMRI analysis revealed significantly increased activation in the
      contralateral SI and ipsilateral motor cortex in elderly subjects. Furthermore,
      we demonstrated age-related reductions in the activity in the SII, ACC, PCC, and
      dorsal parts of the corpus callosum. Our study revealed dramatic age-related
      differences in the processing of a simple tactile stimulus in the somatosensory
      network. Specifically, we detected enhanced activation in the contralateral SI
      and ipsilateral motor cortex assumingly caused by deficient inhibition and
      decreased activation in later stages of somatosensory processing (SII, cingulate
      cortex) in elderly subjects. These results indicate that, in addition to over
      activation to compensate for impaired brain functions, there are complex
      mechanisms of modified inhibition and excitability involved in somatosensory
      processing in the ageing brain.

PMID- 23123142
TI  - Motor, emotional and cognitive deficits in adult BACHD mice: a model for
      Huntington's disease.
AB  - RATIONALE: Huntington's disease (HD) is characterized by progressive motor
      dysfunction, emotional disturbances and cognitive deficits. It is a genetic
      disease caused by an elongation of the polyglutamine repeats in the huntingtin
      gene. Whereas HD is a complex disorder, previous studies in mice models have
      largely been confined to assessing motor deficits. OBJECTIVES: The aim of the
      present studies is a comprehensive phenotypical assessment of not only motor and
      gait deficits, but also of emotional and cognitive deficits in adult BACHD mice.
      MATERIAL AND METHODS: 46 male BACHD mice between 9 and 10 months of age were
      used. Wild type (+/+) and transgenic (+/T) mice were tested for motor deficits on
      a Rotarod and Catwalk system. Emotional deficits were assessed with the zero-maze
      and fear conditioning tests. Cognitive deficits in a strategy shifting task were
      evaluated in a cross-maze test. RESULTS: Comparing +/T and +/+ mice, we
      replicated the motor deficits in the transgenic mice that were previously
      described in the Rotarod test. For the first time, motor coordination imbalances
      in +/T animals are described in the Catwalk gait analysis system. +/T mice showed
      more anxiety-like behavior in the zero-maze test and a higher freezing response
      in the fear conditioning test. Reversal and strategy shifting impairments were
      demonstrated in the cross-maze, indicative of a disturbed prefrontal-striatal
      pathway. CONCLUSION: The results suggest that BACHD mice represent an animal
      model with a high degree of face validity for HD and may be very useful for
      testing novel therapeutic strategies.

PMID- 23123144
TI  - The reciprocal relations between morphological processes and reading.
AB  - Reciprocal relations between emerging morphological processes and reading skills
      were examined in a longitudinal study tracking children from Grade 1 through
      Grade 3. The aim was to examine predictive relationships between productive
      morphological processing involving composing and decomposing of inflections and
      derivations, reading ability for pseudoword and word decoding, and word and
      passage reading comprehension after controlling for initial abilities in reading,
      morphological processing, phonological awareness, and vocabulary. Reciprocal
      influences were indicated by predictive relations among initial morphological
      processes and later reading abilities co-occurring with relationships between
      initial reading abilities and later morphological processes. Using multilevel
      modeling, decomposing and composing were found to predict emerging word decoding
      and word and passage comprehension but not pseudoword decoding. Reading
      comprehension predicted growth in decomposing. Subsequent regression analyses of
      model-estimated early linear growth in predictors and later linear growth in
      outcomes showed that early growth in morphological processes predicted later
      growth in word decoding and passage comprehension. Although reciprocal relations
      between emerging morphological processes and reading skills were observed, the
      different patterns on each side of the reciprocal "coin" indicated that the
      mechanisms underlying predictive influences are likely different but related to
      quality of lexical representations.

PMID- 23123143
TI  - Long-lasting and sex-specific consequences of elevated egg yolk testosterone for
      social behavior in Japanese quail.
AB  - In birds, early exposure to steroid hormones deposited in egg yolks is
      hypothesized to result in long-lasting effects on brain and behavior. However,
      the long-term effects of maternal androgens on the development of social
      behavior, and whether these could interfere with the effects of the endogenous
      gonadal hormones that mediate sexual differentiation, remain poorly known. To
      answer these questions, we enhanced yolk testosterone by injecting testosterone
      (T) in oil into Japanese quail (Coturnix japonica) eggs prior to incubation.
      Vehicle-injected (V) eggs served as controls. From age 3 weeks to 8 weeks, sexual
      development was measured using morphological and physiological traits, and social
      behavior was measured, including male-typical sexual behavior. In females,
      treatment with testosterone boosted growth. Males from T-injected eggs developed
      an affiliative preference for familiar females and differed from V-injected males
      in the acoustic features of their crows, whereas sexual interest (looking
      behavior) and copulatory behavior were not affected. These long-lasting and sex
      specific yolk testosterone effects on the development of dimorphic traits, but
      without disrupting sexual differentiation of reproductive behavior suggest
      potential organizational effects of maternal testosterone, but acting through
      separate processes than the endocrine mechanisms previously shown to control
      sexual differentiation. Separate processes could reflect the action of androgens
      at different times or on multiple targets that are differentially sensitive to
      steroids or develop at different rates.

PMID- 23123145
TI  - Can young children be more accurate predictors of their recall performance?
AB  - Preschoolers persistently predict that they will perform better than they
      actually can perform on a picture recall task. The current investigation sought
      to explore a condition under which young children might be able to improve their
      predictive accuracy. Namely, children were asked to predict their recall twice
      for the same set of items. Children's second predictions were significantly less
      overconfident than their initial predictions for a set of items. However, between
      trials (when the stimulus items changed), children's initial predictions remained
      persistently overconfident. Children appear to have some understanding that past
      performance can predict future performance when predicting for the same set of
      items, but they fail to apply this understanding to new sets of stimuli.

PMID- 23123146
TI  - Reemergence of new variant G3 rotavirus in Japanese pediatric patients, 2009
      2011.
AB  - The molecular epidemiology and characterization of rotaviruses obtained from non
      hospitalized children with acute gastroenteritis in five different prefectures
      (Hokkaido, Saga, Tokyo, Osaka, and Kyoto) from July 2009 to June 2011 was
      investigated. Among 831 fecal specimens tested, rotavirus was found in 165
      specimens (19.9%). The rotavirus detection rate in 2010-2011 (23.3%) was higher
      than those in 2009-2010 (16.0%). The highest prevalence of rotavirus was found in
      children aged 12 to 23 months. Rotavirus could be detected throughout the 8 month
      period with a peak in April. We found that G3P[8] was the most prevalent genotype
      (54.5%), followed by G1P[8] (29.1%), G9P[8] (9.1%), G3P[4] (3.0%), G2P[4] (2.5%),
      G1P[4] (1.2%), and G4P[8] (0.6%), respectively. Interestingly, G3 strains emerged
      as the most predominant genotype and replaced G1 rotavirus which had been
      reported as the most predominant genotype in the previous studies. Phylogenetic
      analysis revealed that G3 rotavirus strains were closely related to the "new
      variant G3" 5091 strain, which emerged in Japan in 2003-2004. A significant
      increase in the prevalence of rotavirus G3 found in this study indicates that
      rotavirus G3 strain is the major cause of infection in five geographical areas of
      Japan and may distribute globally in the near future.

PMID- 23123147
TI  - CNTNAP2 is significantly associated with schizophrenia and major depression in
      the Han Chinese population.
AB  - CNTNAP2, located on 7q35-36.1, encodes a single-pass transmembrane protein
      mediating cell-cell interactions in the nervous system. CNTNAP2 has been
      suggested to play an important role in mental diseases such as autism and
      language disorder. However, we still do not know whether it also confers risk to
      major psychiatric disorders such as schizophrenia, major depression and bipolar
      disorder. We analysed single nucleotide polymorphisms (SNPs) previously reported
      to be associated with autism or language impairment in 1135 schizophrenia
      patients, 1135 unrelated major depression patients, 1135 unrelated bipolar
      disorder patients and 1135 unrelated normal controls recruited from the Han
      Chinese population. We found that the genotypes of rs17236239 were significantly
      associated with schizophrenia and the alleles of rs2710102 and rs2710117 were
      significantly associated with major depression. According to the location of
      significant signals, our study indicated that exon 13-15 of CNTNAP2 may play
      important roles in both schizophrenia and major depression in the Han Chinese
      population.

PMID- 23123148
TI  - Cardiovascular disease prevention in women: a rapidly evolving scenario.
AB  - The past decade has witnessed a long overdue recognition of the importance of CVD
      in women, accompanied by an increasing awareness of gender differences in risk
      factors, natural history, preventive strategies, treatment, and prognosis of CVD.
      Reflecting the disease burden and the specific aspects of CVD in women, the
      American Heart Association has developed women-specific evidence-based guidelines
      and consensus documents for CVD prevention. The most recent update of these
      guidelines, published in 2011, is a milestone in the field and shows the rapidly
      evolving scenario of CVD prevention in women. We discuss some novel aspects of
      the 2011 update. The new guidelines change the focus from evidence-based to
      effectiveness-based, with consideration of both benefits and harms/costs of
      preventive interventions. The guidelines also introduce "ideal cardiovascular
      health" as the lowest category of risk, which implies the need of communitywide
      preventive, educational and policy initiatives to promote healthy lifestyles in
      the general population. Furthermore, the guidelines emphasize long-term overall
      CVD risk rather than short-term coronary risk. We also address several barriers
      and open questions in the evaluation and implementation of these guidelines,
      including how to increase the small proportion of women with ideal cardiovascular
      health; how to increase implementation and compliance with the recommendations;
      how to provide effectiveness-based recommendations for lifetime prevention goals
      based on short-term trials; how to obtain the best possible evidence in women;
      how to identify subgroups of women with different cardiovascular risk profiles or
      who may require tailored preventive strategies; and how to adapt current
      guidelines to international settings, particularly to low- and middle-income
      countries.

PMID- 23123149
TI  - Biomechanical study of the extensor carpi ulnaris as a dynamic wrist stabilizer.
AB  - PURPOSE: To investigate the dynamic stabilizing effect of the extensor carpi
      ulnaris (ECU) on the distal radioulnar joint (DRUJ) and the ulnocarpal joint in a
      simulated model of triangular fibrocartilage complex (TFCC) injury. METHODS:
      Using 8 fresh-frozen cadavers, we fixed the humerus and ulna at 90 degrees  of
      elbow flexion, and the radius and hand were allowed to rotate freely around the
      ulna. Passive mobility was tested by translating the radiocarpal unit relative to
      the ulna along dorsal-palmar directions. Unit displacement was measured by an
      electromagnetic tracking device in different forearm rotations and under varied
      loading to the wrist motor tendons. Magnitudes of displacement were compared
      between different loading patterns of the prime wrist movers in the TFCC
      sectioned wrists. The effect of sectioning the ECU subsheath was analyzed.
      RESULTS: When physiological loads were applied to all of the prime wrist movers,
      the magnitude of displacement during passive mobility testing decreased in
      supination and neutral rotation. After ECU tendon loading was released, mobility
      increased again in supination and neutral rotation. When the load was applied
      only to the ECU tendon, mobility decreased in supination and neutral rotation as
      compared with unloaded. Little change in the mobility was found in pronation
      regardless of the tendon loading pattern. After sectioning of the ECU subsheath,
      the stabilizing effect of the ECU decreased in neutral rotation. CONCLUSIONS: In
      a neutral wrist position with complete sectioning of the TFCC, the ECU
      dynamically stabilized the DRUJ and the ulnocarpal joint in supination and
      neutral forearm rotation. The ECU subsheath assisted ECU tendon stabilization on
      the ulnar side of the wrist, especially in the neutral rotation. CLINICAL
      RELEVANCE: Maintaining the ECU and its subsheath may reduce DRUJ instability in
      patients with TFCC injuries.

PMID- 23123150
TI  - Mild trapezial-metacarpal arthrosis.

PMID- 23123151
TI  - Intermediate-term to long-term outcome of surgically and nonsurgically treated
      congenital, isolated radial head dislocation.
AB  - PURPOSE: Adolescent patients with congenital radial head dislocation presenting
      with pain and limitation in motion might benefit from radial head excision. We
      report objective and patient-rated data for patients treated with radial head
      excision and those followed nonsurgically. We hypothesized that surgery would
      improve pain and motion and that outcomes and the need for additional surgery
      would be similar between the 2 groups. METHODS: We reviewed our surgical logs and
      identified 16 patients (10 treated surgically and 6 treated nonsurgically) for
      participation. At a mean of 10 years for the surgical group and 16 years after
      initial office visit for the nonsurgical group, we collected patient-rated and
      objective data, including range of motion, strength, and pain at the wrist or
      elbow. RESULTS: Eight of 16 patients had bilateral dislocations. Preoperative and
      postoperative elbow flexion (137 degrees  versus 135 degrees ) and extension (27
      degrees  versus 23 degrees ) were unchanged in surgically treated patients.
      Forearm rotation was improved after surgery (100 degrees  versus 119 degrees ).
      Carrying angle was similar between surgical (17 degrees ) and nonsurgical (13
      degrees ) elbows, but surgically treated elbows had significantly different ulnar
      variance at +4.9 mm compared to -0.4 mm for the nonsurgically treated patients.
      Surgically treated patients had significant improvement in elbow pain following
      radial head excision. Final Quick Disabilities of the Arm, Shoulder, and Hand
      scores were similar between groups, although there were lower mean scores among
      nonsurgically treated patients. CONCLUSIONS: Radial head excision in patients
      with symptomatic, isolated, congenital radial head dislocations resulted in
      substantial pain relief and patient satisfaction but modest improvement in
      forearm rotation and no improvement in elbow flexion-extension. Furthermore, more
      than 25% of the surgically treated limbs developed wrist pain and needed
      additional surgery. The nonsurgical group did not lose motion, develop pain, or
      need surgery. This information might help make the decision whether to excise the
      radial head in patients with symptomatic, congenital radial head dislocation.

PMID- 23123152
TI  - Management of geriatric distal radius fractures.

PMID- 23123153
TI  - Arsenic urinary speciation in Mthfr deficient mice injected with sodium arsenate.
AB  - In most mammalian species, arsenic biotransformation occurs primarily by
      biomethylation and reduction reactions, with dimethylarsinic acid being the
      predominant metabolite excreted in the urine. Methylenetetrahydrofolate reductase
      (Mthfr) plays a key role in folate metabolism by channeling one-carbon units
      between nucleotide synthesis and methylation reactions. In the study on
      transgenic Mtfhr knockout mice we investigated: (1) whether Mthfr is an important
      determinant in arsenic biotransformation by performing urinary arsenic
      speciation, and (2) whether dietary folate deficiency alters arsenic
      biotransformation in these mice. The Mthfr mice fed folate replete or folate
      deficient diet were injected with sodium arsenate 1mg/kg, and placed in metabolic
      cages for a urine collection. The urine was analyzed for arsenic species.
      Additionally, folate and homocysteine plasma level was analyzed in Mthfr mice.
      When fed a folate control diet, the Mthfr(-/-) mice excreted significantly less
      of the total arsenic in urine than did the Mthfr(+/+) and Mthfr(+/-) mice. The
      Mthfr(-/-) had significantly lower levels of pentavalent arsenic in their urine
      than did the Mthfr(+/+)mice. The wild type mice excreted significantly less
      pentavalent arsenic when they were fed folate deficient diet comparing to control
      diet. The current data suggest that both the Mthfr status and food folate level
      modulate in a significant manner excretion of arsenic in mice, following
      intraperitoneal administration of sodium arsenate.

PMID- 23123154
TI  - A chronic oral exposure of pigs with deoxynivalenol partially prevents the acute
      effects of lipopolysaccharides on hepatic histopathology and blood clinical
      chemistry.
AB  - Lipopolysaccharides (LPS), a cell wall component of gram-negative bacteria, and
      deoxynivalenol (DON), a prevalent Fusarium-derived contaminant of cereal grains,
      are each reported to have detrimental effects on the liver. A potentiating toxic
      effect of the combined exposure was reported previously in a mouse model and
      hepatocytes in vitro, but not in swine as the most DON-susceptible species. Thus,
      pigs were fed either a control diet (CON) or a Fusarium contaminated diet (DON,
      3.1mg DON/kg diet) for 37 days. At day 37 control pigs were infused for 1h either
      with physiological saline (CON_CON), 100MUg/kg BW DON (CON_DON), 7.5MUg/kg BW LPS
      (CON_LPS), or both toxins (CON_DON/LPS) and Fusarium-pigs with saline (DON_CON)
      or 7.5MUg/kg BW LPS (DON_LPS). Blood samples were taken before and after infusion
      (-30, +30, +60, +120, and +180min) for clinical blood chemistry. Pigs were
      sacrificed at +195min and liver histopathology was performed. LPS resulted in
      higher relative liver weight (p<0.05), portal, periportal and acinar inflammation
      (p<0.05), haemorrhage (p<0.01) and pathological bilirubin levels (CON_CON
      1.0MUmol/L vs. CON_LPS 5.4MUmol/L, CON_DON/LPS 8.3MUmol/L; p<0.001). DON feeding
      alleviated effects of LPS infusion on histopathology and blood chemistry to
      control levels, whereas DON infusion alone had no impact.

PMID- 23123155
TI  - Staphylococcus aureus infection of intestinal epithelial cells induces human
      umbilical cord-derived mesenchymal stem cell migration.
AB  - There is a growing interest in umbilical cord blood (UCB)-derived mesenchymal
      stem cells (MSCs) for cellular therapy in regenerative medicine. To aid in tissue
      repair, MSCs are recruited to sites of inflammation induced by a bacterial
      infection. The primary objective of this study was to explore the mechanisms of
      MSC recruitment to intestinal epithelial cells infected with Staphylococcus
      aureus. First, we isolated and characterized the UCB-derived MSCs used in our
      experiments. Next, we determined the ability of S. aureus infected intestinal
      epithelial cells to induce migration of UCB-derived MSCs. Expression analysis of
      cytokines secreted by infected epithelial cells indicated that MSC migration
      occurred predominately via a nuclear factor-kappa B (NF-kappaB)-dependent
      signaling pathway. Altogether, our data provide the first evidence for a role of
      S. aureus infection in MSC migration and reveal the function of UCB-derived MSCs
      in intestinal pathophysiology.

PMID- 23123156
TI  - The postnatal support needs of mothers with an intellectual disability.
AB  - OBJECTIVE: there is growing evidence that many parents with intellectual
      disabilities can parent successfully when given adequate support. This paper aims
      to explore the postnatal care experiences of mothers with an intellectual
      disability. DESIGN: a qualitative design was used and data were collected using a
      semi-structured interview format and analysed using Interpretative
      Phenomenological Analysis. SETTING: the study took place in community settings in
      Scotland. PARTICIPANTS: six mothers with intellectual disabilities were
      interviewed about their experiences. MEASUREMENTS AND FINDINGS: two super
      ordinate themes are discussed with accompanying subthemes: challenges of
      providing support and how support was delivered. KEY CONCLUSIONS: the mothers
      valued formal postnatal care, but this was secondary to informal support. How
      mothers perceived the support impacted on its effectiveness and building
      effective relationships with professionals presented challenges. IMPLICATIONS FOR
      PRACTICE: the study suggests the structure and quality of the wider support
      networks of mothers with an intellectual disability are central and should be
      taken account of by professionals. Providing information and advice in ways that
      validates the mother's role is also important, particularly as the mother's
      perception of how help is given can impact on the degree to which mothers engage
      with professionals.

PMID- 23123157
TI  - Care providers' views and experiences of postnatal care in private hospitals in
      Victoria, Australia.
AB  - OBJECTIVE: in Australia, as in other developed countries, women have consistently
      reported lower levels of satisfaction with postnatal care compared with antenatal
      and intrapartum care. However, in Victoria Australia, women who receive private
      hospital postnatal care have rated their care more favourably than women who
      received public hospital care. This study aimed to gain a further understanding
      of this by exploring care providers' views and experiences of postnatal care in
      private hospitals. DESIGN: qualitative design using semi-structured interviews
      and thematic analysis. SETTING: private maternity hospitals in Victoria,
      Australia. PARTICIPANTS: eleven health-care providers from three metropolitan and
      one regional private hospital including eight midwives (two maternity unit
      managers and six clinical midwives) and three obstetricians. FINDINGS: two global
      themes were identified: 'Constrained Care' and 'Consumer Care'. 'Constrained
      care' demonstrates the complexity of the provision of postnatal care and
      encompasses midwives' feelings of frustration with the provision of postnatal
      care in a busy environment complicated by staffing difficulties, a lack of
      continuity and the impact of key players in postnatal care (including visitors,
      management and obstetricians). 'Consumer care' describes care providers' views
      that women often approach private postnatal care as a consumer, which can impact
      on their expectations and satisfaction with postnatal care. Despite these
      challenges, care providers, particularly midwives, highly valued (and generally
      enjoyed working in) postnatal care. KEY CONCLUSIONS: this study, along with other
      Australian and international studies, has identified that hospital postnatal care
      is complex and characterised by multiple barriers which impact on the provision
      of quality postnatal care. Further research is needed to evaluate routine
      postnatal practices and continuity of care within the postnatal period. In-depth
      qualitative studies investigating women's expectations and experiences of
      postnatal care in both the public and private sector are also needed.

PMID- 23123158
TI  - Mitochondrial fragmentation caused by phenanthroline promotes mitophagy.
AB  - Mitochondrial dynamics and mitophagy are thought to be important events for the
      quality control of mitochondria and mitochondria-associated diseases. To identify
      novel mitophagy modulators, we developed a cell-based screening system and
      selected 1,10-phenanthroline (Phen) as a target molecule. Phen treatment highly
      induced mitochondrial fragmentation and mitochondrial dysfunctions in a Drp1
      dependent manner. Phen treatment also increased autophagy. Moreover, prolonged
      exposure of Phen increased mitochondria clearance through mitophagy. Phen
      mediated loss of mitochondrial mass was more reduced in ATG5 deficient cells than
      in wild type cells. In addition, down-regulation of Drp1 decreased autophagy
      activation, suggesting that mitochondrial fission is involved in Phen-mediated
      mitophagy. Thus, our results demonstrate that the disruption of mitochondrial
      dynamics and mitochondrial dysfunctions provokes mitophagy in Phen-treated cells.

PMID- 23123159
TI  - Thioredoxin-like protein TlpA from Bradyrhizobium japonicum is a reductant for
      the copper metallochaperone ScoI.
AB  - TlpA and ScoI of Bradyrhizobium japonicum are membrane-anchored thioredoxin-like
      proteins oriented towards the periplasm. TlpA is a protein-disulfide reductase.
      ScoI is a copper chaperone for cytochrome oxidase biogenesis. TlpA with its
      negative redox potential (E(o') -256 mV) was shown here to reduce oxidized ScoI,
      for which we determined a less negative E(o') (-160 mV). The fast forward
      reaction (rate constant 9.4*10(4) M(-1) s(-1)) was typical for physiologically
      relevant disulfide exchange reactions. A transient TlpA-ScoI heterodisulfide
      formed between Cys107 of TlpA's active site (C(107)XXC(110)) and Cys78 of ScoI's
      copper-binding site (C(74)XXXC(78)). We conclude that TlpA recycles ScoI to the
      dithiol form prior to metallation.

PMID- 23123160
TI  - Meprins process matrix metalloproteinase-9 (MMP-9)/gelatinase B and enhance the
      activation kinetics by MMP-3.
AB  - Meprin alpha and beta, members of the astacin family of zinc metalloproteinases,
      are unique plasma membrane and secreted proteases known to cleave a wide range of
      biological substrates involved in inflammation, cancer and fibrosis. In this
      study, we identified proMMP-9 as a novel substrate and show that aminoterminal
      meprin-mediated clipping improves the activation kinetics of proMMP-9 by MMP-3,
      an efficient activator of proMMP-9. Interestingly, the NH(2)-terminus LVLFPGDL,
      generated by incubation with meprin alpha, is identical to the form produced in
      conditioned media from human neutrophils and monocytes. Hence, this meprin
      mediated processing and enhancement of MMP-9 activation kinetics may have
      biological relevance in the context of in vivo inflammatory processes.

PMID- 23123161
TI  - Development and systematic validation of qPCR assays for rapid and reliable
      differentiation of Xylella fastidiosa strains causing citrus variegated
      chlorosis.
AB  - The xylem-limited, Gram-negative, fastidious plant bacterium Xylella fastidiosa
      is the causal agent of citrus variegated chlorosis (CVC), a destructive disease
      affecting approximately half of the citrus plantations in the State of Sao Paulo,
      Brazil. The disease was recently found in Central America and is threatening the
      multi-billion U.S. citrus industry. Many strains of X. fastidiosa are pathogens
      or endophytes in various plants growing in the U.S., and some strains cross
      infect several host plants. In this study, a TaqMan-based assay targeting the 16S
      rDNA signature region was developed for the identification of X. fastidiosa at
      the species level. Another TaqMan-based assay was developed for the specific
      identification of the CVC strains. Both new assays have been systematically
      validated in comparison with the primer/probe sets from four previously published
      assays on one platform and under similar PCR conditions, and shown to be
      superior. The species specific assay detected all X. fastidiosa strains and did
      not amplify any other citrus pathogen or endophyte tested. The CVC-specific assay
      detected all CVC strains but did not amplify any non-CVC X. fastidiosa nor any
      other citrus pathogen or endophyte evaluated. Both sets were multiplexed with a
      reliable internal control assay targeting host plant DNA, and their diagnostic
      specificity and sensitivity remained unchanged. This internal control provides
      quality assurance for DNA extraction, performance of PCR reagents, platforms and
      operators. The limit of detection for both assays was equivalent to 2 to 10 cells
      of X. fastidiosa per reaction for field citrus samples. Petioles and midribs of
      symptomatic leaves of sweet orange harbored the highest populations of X.
      fastidiosa, providing the best materials for detection of the pathogen. These new
      species specific assay will be invaluable for molecular identification of X.
      fastidiosa at the species level, and the CVC specific assay will be very powerful
      for the specific identification of X. fastidiosa strains that cause citrus
      variegated chlorosis.

PMID- 23123162
TI  - Treatment responses for disseminated intravascular coagulation in 25 children
      treated with recombinant thrombomodulin: a single institution experience.
AB  - INTRODUCTION: Recombinant thrombomodulin (rTM), which degrades factors Va and
      VIIIa by activating protein C, has been developed as a new drug for treating
      disseminated intravascular coagulation (DIC). MATERIALS AND METHODS: Since July
      2009, we have treated 25 children with DIC using rTM (380 U/kg/day, or 130
      U/kg/day for newborns) as a first-line therapy. Median duration of rTM
      administration was 5 consecutive days (range, 2-13 days). We employed DIC
      criteria of the Japan Welfare and Health Ministry. The first day on which rTM
      treatment was given was defined as day 1. RESULTS: Median patients age was 3
      years. Underlying diseases were hematological disorders (n=13) and severe
      infection (n=12). Overall, 20 of the 25 patients had recovered from DIC by day 7
      and 22 of the 25 patients remained alive at day 28. Median Pediatric Logistic
      Organ Dysfunction score improved from 11 on day 1 to 2 on day 7 (p=0.009).
      Laboratory data (median) on day 7 (prothrombin time (PT) ratio, 1.15; fibrin and
      fibrinogen degradation products (FDP), 9.6 mg/l; D-dimer, 1.6 mg/l FEU;
      antithrombin, 112%; protein C, 105%) were significantly improved compared to
      results on day 1 (PT ratio, 1.39; FDP, 21.6 mg/l; D-dimer, 6.4 mg/l FEU;
      antithrombin, 86%; protein C, 54%). Whereas, 5 patients failed to respond and
      serious bleeding events were observed in 2 newborns. CONCLUSION: The efficacy of
      rTM cannot be assessed from the present dataset, due to several limitations such
      as the small heterogenous patient cohort, and the lack of age- and disease
      matched controls. Nevertheless, this case-series remains important in terms of
      enabling further prospective control studies to evaluate the efficacy of rTM in
      children.

PMID- 23123163
TI  - Congenital heart disease in maternal PKU.

PMID- 23123164
TI  - Photochemistry and electrochemistry of anticancer uracils.
AB  - The redox mechanism and electronic absorption behavior of a commercial anticancer
      drug, 5-fluorouracil (5-FU) and two potential anticancer drugs, 2-thiouracil (2
      TU) and dithiouracil (DTU) have been investigated in a wide pH range by UV-Vis
      spectroscopy, cyclic voltammetry and differential pulse voltammetry. The effect
      of electrolytes, substituents, successive sweeps and potential scan rate on the
      voltammetric response of uracils was examined. Organized structure-activity
      relationships of these drugs were established on the basis of the results
      obtained from electronic absorption spectroscopy and cyclic voltammetry. The
      electrode reaction mechanism was suggested using the experimentally determined
      electrochemical parameters. The DNA binding propensity of uracils was found
      greater than the classical intercalator, proflavin and clinically used drug,
      epirubicin. Moreover, the results obtained through ab initio calculations for the
      oxidation potential of the three uracil derivatives were found in good agreement
      with the electrochemical results.

PMID- 23123165
TI  - Brainstem nutrient sensing in the nucleus of the solitary tract inhibits feeding.
AB  - Direct detection of circulating nutrients by the central nervous system has been
      implicated in the regulation of energy balance, and the mediobasal hypothalamus
      is considered as the primary sensing site mediating these effects. Neurons
      sensitive to energyrelated signals have also been identified outside the
      hypothalamus, particularly within the caudomedial nucleus of the solitary tract
      (cmNTS) in brainstem, but the consequences of direct cmNTS nutrient detection on
      energy balance remain poorly characterized. Here we determined the behavioral and
      metabolic consequences of direct L-leucine detection by the cmNTS and
      investigated the intracellular signaling and neurochemical pathways implicated in
      cmNTS L-leucine sensing in rats. Our results support the distributed nature of
      central nutrient detection, evidence a role for the cmNTS S6K1 pathway in the
      regulation of meal size and body weight, and suggest that the cmNTS integrates
      direct cmNTS nutrient detection with gut-derived, descending forebrain, and
      adiposity signals of energy availability to regulate food intake.

PMID- 23123166
TI  - A randomized controlled trial comparing a multimodal intervention and standard
      obstetrics care for low back and pelvic pain in pregnancy.
AB  - OBJECTIVE: Women commonly experience low back pain during pregnancy. We examined
      whether a multimodal approach of musculoskeletal and obstetric management (MOM)
      was superior to standard obstetric care to reduce pain, impairment, and
      disability in the antepartum period. STUDY DESIGN: A prospective, randomized
      trial of 169 women was conducted. Baseline evaluation occurred at 24-28 weeks'
      gestation, with follow-up at 33 weeks' gestation. Primary outcomes were the
      Numerical Rating Scale (NRS) for pain and the Quebec Disability Questionnaire
      (QDQ). Both groups received routine obstetric care. Chiropractic specialists
      provided manual therapy, stabilization exercises, and patient education to MOM
      participants. RESULTS: The MOM group demonstrated significant mean reductions in
      Numerical Rating Scale scores (5.8 +/- 2.2 vs 2.9 +/- 2.5; P < .001) and Quebec
      Disability Questionnaire scores (4.9 +/- 2.2 vs 3.9 +/- 2.4; P < .001) from
      baseline to follow-up evaluation. The group that received standard obstetric care
      demonstrated no significant improvements. CONCLUSION: A multimodal approach to
      low back and pelvic pain in mid pregnancy benefits patients more than standard
      obstetric care.

PMID- 23123167
TI  - Prenatal treatment of congenital adrenal hyperplasia: risks outweigh benefits.
AB  - Prenatal treatment of congenital adrenal hyperplasia by administering
      dexamethasone to a woman presumed to be carrying an at-risk fetus has been
      described as safe and effective in several reports. A review of data from animal
      experimentation and human trials indicates that first-trimester dexamethasone
      decreases birthweight; affects renal, pancreatic beta cell, and brain
      development; increases anxiety; and predisposes to adult hypertension and
      hyperglycemia. In human studies, first-trimester dexamethasone is associated with
      orofacial clefts, decreased birthweight, poorer verbal working memory, and poorer
      self-perception of scholastic and social competence. Numerous medical societies
      have cautioned that prenatal treatment of congenital adrenal hyperplasia with
      dexamethasone should only be done in prospective clinical research settings with
      institutional review board approval, and therefore is not appropriate for routine
      community practice.

PMID- 23123168
TI  - Molecular epidemiology of amoebiasis in Malaysia: highlighting the different risk
      factors of Entamoeba histolytica and Entamoeba dispar infections among Orang Asli
      communities.
AB  - Currently, species-specific information on Entamoeba infections is unavailable in
      Malaysia and is restricted worldwide due to the re-description of pathogenic
      Entamoeba histolytica and non-pathogenic Entamoeba dispar and Entamoeba
      moshkovskii. Therefore, this cross-sectional study was conducted to provide the
      first known documented data on the true prevalence of these three species in
      western Malaysia using a molecular method. Another aim of this study was to
      determine the association of potential risk factors associated with each
      Entamoeba sp. A total of 500 stool samples from three Orang Asli tribes were
      randomly collected. The overall prevalence of E. histolytica, E. dispar and E.
      moshkovskii determined by microscopy was 18.6% (93/500). Molecular analysis
      revealed that while most Entamoeba-positive individuals were infected with E.
      dispar (13.4%), followed by E. histolytica (3.2%) and E. moshkovskii (1.0%), the
      present findings show low prevalence rates of mixed infections with E.
      histolytica and E. dispar (2%), E. dispar and E. moshkovskii (1.2%) and
      association infections of E. histolytica, E. dispar and E. moshkovskii (0.4%).
      Logistical regression analysis indicates that the dynamics of the transmission of
      the three Entamoeba spp. was different. Of six statistically significant
      variables observed in the univariate analysis, three were retained as significant
      risk factors for E. histolytica infection in the logistical regression model.
      These factors were (i) not washing hands after playing with soil or gardening
      (Odds ratio (OR)=4.7; 95% confidence level (CI)=1.38, 16.14; P=0.013), (ii)
      indiscriminate defecation in the river or bush (OR=5.7; 95% CI=1.46, 21.95;
      P=0.012) and (iii) close contact with domestic animals (OR=5.4; 95% CI=1.36,
      2.51; P=0.017). However, subjects with family members who were infected with E.
      histolytica/E. dispar/E. moshkovskii (OR=3.8; 95 CI=2.11, 6.86; P<0.001) and
      those who consumed raw vegetables (OR=1.8; 95% CI=1.01, 3.23; P=0.047) were more
      likely to be infected with E. dispar. On the other hand, no associated factor was
      identified with E. moshkovskii infection. Nevertheless, diarrhoea (P=0.002) and
      other gastroenteritis symptoms (P<0.001) were only associated with E. histolytica
      infection. The present study provides new insight into the distribution and risk
      factors of E. histolytica, E. dispar and E. moshkovskii infections among Orang
      Asli communities in Malaysia. Identifying the different risk factors of E.
      histolytica and E. dispar infections will help in the planning specific
      strategies in the control and prevention of each infection in the communities.
      Moreover, it emphasises the need for molecular methods to determine the species
      specific prevalence of Entamoeba spp.

PMID- 23123169
TI  - Modelling the social determinants of health and simulating short-term and long
      term intervention impacts for the city of Toronto, Canada.
AB  - There is a substantial body of evidence highlighting the importance of the social
      determinants of health in shaping the health of urban populations in Canada. The
      low socio-economic status of marginalized, disadvantaged, and precarious
      populations in urban settings has been linked to adverse health outcomes
      including chronic and infectious disease, negative health behaviours, barriers to
      accessing health care services, and overall mortality. Given the dynamic
      complexities and inter-relationships surrounding the underlying drivers of
      population health outcomes and inequities, it is difficult to assess program and
      policy intervention tradeoffs, particularly when such interventions are studied
      with static models. To address this challenge, we have adopted a systems science
      approach and developed a simulation model for the City of Toronto, Canada,
      utilizing system dynamics modelling methodology. The model simulates changes in
      health, social determinants, and disparities from 2006 and projects forward to
      2046 under different assumptions. Most of the variables in the model are
      stratified by ethnicity, immigration status, and gender, and capture the
      characteristics of adults aged 25-64. Intervention areas include health care
      access, behaviour, income, housing, and social cohesion. The model simulates
      alternative scenarios to help demonstrate the relative impact of different
      interventions on poor health outcomes such as chronic disease rates, disability
      rates, and mortality rate. It gives insight into how much, and how quickly,
      interventions can reduce mortality and morbidity. We believe this will serve as a
      useful learning tool to allow diverse stakeholders and policy makers to ask "what
      if" questions and map effective policy directions for complex population health
      problems, and will enable communities to think about their health futures. 

PMID- 23123170
TI  - A Plasmodium multi-domain protein possesses multiple inositol phosphate kinase
      activities.
AB  - The synchronization of intraerythrocytic maturation of Plasmodium parasites is an
      important factor in the malaria infection process. Synchronization is mediated by
      inositol phosphate (InsP(x))-induced Ca(2+)-release from internal stores. To
      further investigate the InsP(x) metabolism in these parasites a Plasmodium
      protein possessing inositol phosphate kinase (IPK) activity was recombinantly
      expressed, purified and enzymatically characterized for the first time. Its main
      activity is the conversion of the Ca(2+)-releasing second messenger
      Ins(1,4,5)P(3) to Ins(1,3,4,5)P(4), an important factor in chromatin remodeling
      and also in Ca(2+)-release. This protein possesses several additional IPK
      activities pointing to a potential role as inositol phosphate multikinase.
      Interestingly, we have also identified three putative subdomains of histone
      deacetylase in this protein possibly linking InsP(x)- and acetylation-mediated
      transcription regulation. Furthermore, we examined the inhibitory potential of
      >40 polyphenolic substances against its kinase activity. Because of the important
      role of InsP(x)-induced Ca(2+)-release in the development of Plasmodium
      parasites, IPKs are interesting targets for novel antimalarial approaches.

PMID- 23123171
TI  - The novel HSP90 inhibitor, PU-H71, suppresses glial cell activation but weakly
      affects clinical signs of EAE.
AB  - Ansamycins are very effective HSP90 inhibitors that showed significant beneficial
      effects in the treatment of EAE. However, their toxicity and poor stability in
      solution limit their clinical use. In the present study we have characterized the
      anti-inflammatory properties of a novel HSP90 inhibitor, PU-H71, and tested its
      effects in EAE. Our findings show that PU-H71 reduced lipopolysaccharide
      astrocyte activation but failed to reduce the inflammatory cytokine activation.
      In contrast to ansamycins, PU-H71 weakly affects EAE clinical course. In
      conclusion, although PU-H71 displayed some anti-inflammatory properties, it
      appeared in vivo less effective than the more toxic HSP90 inhibitors.

PMID- 23123172
TI  - Complete canine papillomavirus life cycle in pigmented lesions.
AB  - Canine papillomaviruses (CPVs) have been identified in various benign and
      malignant neoplastic skin disorders. The most frequent manifestations of CPV
      infections are classical warts and pigmented plaques. Although the etiology of
      canine oral papillomatosis is well established, knowledge about CPVs role in the
      development of pigmented plaques remains vague. Indeed, as CPV DNA may frequently
      be found on clinically healthy canine skin, its mere detection in lesions cannot
      be regarded as a sufficient indicator of causality. Whether CPVs are actually
      active in pigmented plaques, a requirement for any conceivable involvement, is
      consequently an open question. To inquire such viral activity, two distinct
      clinical cases of canine pigmented lesions were evaluated in greater detail. The
      histological findings in the two cases supported the clinical diagnosis of
      pigmented viral plaques. Sequencing of amplified DNA from these lesions revealed
      the genomes of two novel CPV types, i.e. CPV9 and CPV14, both putatively
      belonging to the genus Chi. Furthermore, transcription and splicing of
      corresponding CPV mRNA could be shown by RT-PCR in the respective lesions.
      Finally, viral particles were detected by electron microscopy in homogenates as
      well as in nuclei of keratinocytes in pigmented lesions. In conclusion, the
      results link clinical signs of pigmented plaques to histological changes, the
      presence of CPV specific DNA, viral gene transcription, and the presence of viral
      particles in and from the lesions. Thus, the findings outline the entire
      replicative cycle of CPVs in pigmented plaques, which might help understanding
      the relationship between these viruses and the associated disorders.

PMID- 23123173
TI  - First evidence of hemoplasma infection in free-ranging Namibian cheetahs
      (Acinonyx jubatus).
AB  - Infections with feline hemotropic mycoplasmas (hemoplasmas) have been documented
      in domestic cats and free-ranging feline species with high prevalences in Iberian
      lynxes (Lynx pardinus), Eurasian lynxes (Lynx lynx), European wildcats (Felis
      silvestris silvestris), African lions (Panthera leo) in Tanzania and domestic
      cats in South Africa. The prevalence of hemoplasmas has not yet been investigated
      in free-ranging felids in southern Africa. In this study we screened 73 blood
      samples from 61 cheetahs in central Namibia for the presence of hemoplasmas using
      quantitative real-time PCR. One of the cheetahs tested PCR-positive. Phylogenetic
      analysis based on partial sequencing of the 16S rRNA and RNAse P genes revealed
      that the isolate belongs to the Mycoplasma haemofelis/haemocanis group. This is
      the first molecular evidence of a hemoplasma infection in a free-ranging cheetah.

PMID- 23123174
TI  - Enhanced replication of swine influenza viruses in dexamethasone-treated juvenile
      and layer turkeys.
AB  - Frequent transmission of swine influenza viruses (SIVs) to turkeys has been
      reported since 1980s. Experimental studies also showed that SIVs can infect
      turkeys with varying replication and transmission efficiency depending on the
      strain. However, host factors involved in infection/replication efficiency remain
      unclear. To investigate whether the immune status of turkeys might play a role in
      the susceptibility of turkeys to SIVs, we studied the replication efficiency of
      two recent SIVs (human-like H1N2 and triple reassortant (TR) H3N2) in
      dexamethasone-treated turkeys. The viruses were inoculated intranasally in both
      dexamethasone-treated and untreated control juvenile and layer turkeys. Amount of
      virus shedding was monitored at 2, 4, and 7 days post inoculation (DPI).
      Additionally, passage of both viruses was attempted in dexamethasone-treated 4
      week-old turkeys. In both juvenile and layer turkeys, we were able to detect
      human-like H1N2 SIV only from dexamethasone-treated turkeys and no virus was
      detected in untreated birds. The virus shedding of the TR H3N2 SIV was also
      consistently higher (~ 1 Log(10)EID(50)/ml) in dexamethasone-treated birds in
      both tracheal and cloacal swabs compared to untreated birds. Virus passage in
      dexamethasone-treated turkeys was successful up to the second passage and no
      virus was recovered from the third passage. These results show that potential
      immunosuppression due to dexamethasone treatment may enhance the transmission and
      adaptation of SIVs in turkeys through enhancement of virus replication, prolonged
      virus shedding, and possible decrease of infectious dose required to initiate
      infection.

PMID- 23123175
TI  - Characterisation of early and late bovine papillomavirus protein expression in
      equine sarcoids.
AB  - Sarcoids are common skin tumours of horses and donkeys that are characterised by
      persistent proliferation of dermal fibroblasts associated with the presence of
      bovine papillomavirus (BPV) DNA. Some early BPV proteins have been demonstrated
      within sarcoids and RNA containing both early and late transcripts is present,
      yet it remains unclear whether late replication of BPV, culminating in the
      production of infectious virus particles, can occur in equids. Here we report
      that BPV1 RNA isolated from equine sarcoids encodes a unique deletion of four
      residues within the L2 protein suggesting a novel variant of virus has evolved in
      equines. Such viral evolution would require the production and transmission of
      virus particles among horses with sarcoids. Quantitative RT-PCR demonstrated the
      presence of mRNA transcripts containing early gene message in sarcoid tissues and
      BPV-E2 early virus antigen was detected by immunofluorescence in the nuclei of
      dermal fibroblasts, but no E2 expression could be detected within the overlying
      epidermis where productive virus replication would be expected to occur. Although
      immunohistochemistry clearly detected late virus proteins in the nuclei of dermal
      cells from samples of bovine papillomas, no late protein expression was detected
      in formalin-fixed tissue from equine sarcoids; either in the dermis or epidermis.
      Moreover, quantitative RT-PCR demonstrated that late gene mRNA represented <0.3%
      of the transcribed BPV RNA. We conclude that BPV does not undergo productive
      infection in the epidermis overlying equine sarcoids at levels comparable with
      that occurring in its natural bovine host.

PMID- 23123176
TI  - Emerging outbreaks associated with equine coronavirus in adult horses.
AB  - The purpose of this study was to describe clinical, hematological and fecal PCR
      results from 161 horses involved in outbreaks associated with ECoV. The outbreaks
      happened at four separate boarding facilities between November 2011 and April
      2012 in the States of CA, TX, WI and MA. Following the molecular detection of
      ECoV in the feces from the initial index cases, the remaining herdmates were
      closely observed for the development of clinical signs. Fecal samples were
      collected from sick and healthy horses for the PCR detection of ECoV. All four
      outbreaks involved primarily adult horses. Fifty-nine horses developed clinical
      signs with 12-16 sick horses per outbreak. The main clinical signs reported were
      anorexia, lethargy and fever. Four horses from 3 different outbreaks were
      euthanized or died due to rapid progression of clinical signs. The cause of death
      could not be determined with necropsy evaluation in 2 horses, while septicemia
      secondary to gastrointestinal translocation was suspected in 2 horses. Blood work
      was available from 10 horses with clinical disease and common hematological
      abnormalities were leucopenia due to neutropenia and/or lymphopenia. Feces were
      available for ECoV testing by real-time PCR from 44 and 96 sick and healthy
      horses, respectively. 38/44 (86%) horses with abnormal clinical signs tested PCR
      positive for ECoV, while 89/96 (93%) healthy horses tested PCR negative for ECoV.
      The overall agreement between clinical status and PCR detection of ECoV was 91%.
      The study results suggest that ECoV is associated with self-limiting clinical and
      hematological abnormalities in adult horses.

PMID- 23123177
TI  - Oxidative stress and cancer: an overview.
AB  - Reactive species, which mainly include reactive oxygen species (ROS), are
      products generated as a consequence of metabolic reactions in the mitochondria of
      eukaryotic cells. In normal cells, low-level concentrations of these compounds
      are required for signal transduction before their elimination. However, cancer
      cells, which exhibit an accelerated metabolism, demand high ROS concentrations to
      maintain their high proliferation rate. Different ways of developing ROS
      resistance include the execution of alternative pathways, which can avoid large
      amounts of ROS accumulation without compromising the energy demand required by
      cancer cells. Examples of these processes include the guidance of the glycolytic
      pathway into the pentose phosphate pathway (PPP) and/or the generation of lactate
      instead of employing aerobic respiration in the mitochondria. Importantly, ROS
      levels can be used as a thermostat to monitor the damage that cells can bear. The
      implications for ROS regulation are highly significant for cancer therapy because
      commonly used radio- and chemotherapeutic drugs influence tumor outcome through
      ROS modulation. Moreover, the discovery of novel biomarkers that are able to
      predict the clinical response to pro-oxidant therapies is a crucial challenge to
      overcome to allow for the personalization of cancer therapies.

PMID- 23123178
TI  - Amino acid signatures in the Ovar-DRB1 peptide-binding pockets are associated
      with Ovine Pulmonary Adenocarcinoma susceptibility/resistance.
AB  - Potential relationships between amino acid motifs of various alleles of the ovine
      major histocompatibility complex DR (Ovar-DR) molecule and occurrence of clinical
      OPA caused by JSRV were investigated in a case-control study. Latxa sheep (n=132)
      screened for presence/absence of pulmonary OPA lesions were typed for their Ovar
      DRB1 2nd exon alleles by PCR and sequence-based typing (PCR-SBT). The polymorphic
      amino acid residues derived from the obtained 34 DRB1 protein variants were
      subjected to a logistic regression-based association study. The amino acids at
      several positions showed significant associations with the presence/absence of
      pulmonary OPA lesions; some of the residues were located within the peptide
      binding cleft of the DRB molecule, including pockets P1, P4, P7 and P9.

PMID- 23123179
TI  - Impact of environment on mosquito response to pyrethroid insecticides: facts,
      evidences and prospects.
AB  - By transmitting major human diseases such as malaria, dengue fever and
      filariasis, mosquito species represent a serious threat worldwide in terms of
      public health, and pose a significant economic burden for the African continent
      and developing tropical regions. Most vector control programmes aiming at
      controlling life-threatening mosquitoes rely on the use of chemical insecticides,
      mainly belonging to the pyrethroid class. However, resistance of mosquito
      populations to pyrethroids is increasing at a dramatic rate, threatening the
      efficacy of control programmes throughout insecticide-treated areas, where
      mosquito-borne diseases are still prevalent. In the absence of new insecticides
      and efficient alternative vector control methods, resistance management
      strategies are therefore critical, but these require a deep understanding of
      adaptive mechanisms underlying resistance. Although insecticide resistance
      mechanisms are intensively studied in mosquitoes, such adaptation is often
      considered as the unique result of the selection pressure caused by insecticides
      used for vector control. Indeed, additional environmental parameters, such as
      insecticides/pesticides usage in agriculture, the presence of anthropogenic or
      natural xenobiotics, and biotic interactions between vectors and other organisms,
      may affect both the overall mosquito responses to pyrethroids and the selection
      of resistance mechanisms. In this context, the present work aims at updating
      current knowledge on pyrethroid resistance mechanisms in mosquitoes and compiling
      available data, often from different research fields, on the impact of the
      environment on mosquito response to pyrethroids. Key environmental factors, such
      as the presence of urban or agricultural pollutants and biotic interactions
      between mosquitoes and their microbiome are discussed, and research perspectives
      to fill in knowledge gaps are suggested.

PMID- 23123180
TI  - Ionic liquids as ingredients in topical drug delivery systems.
AB  - Because of their properties, ionic liquids (ILs) (Ranke et al.) offer many
      advantages in topical drug delivery systems. For example, ionic liquids can be
      used to increase the solubility of sparingly soluble drugs and to enhance their
      topical and transdermal delivery. Furthermore, ILs can be used either to
      synthesize active pharmaceutical ingredients or as antimicrobial ingredients. In
      the present work, the conventional oil-in-water (O/W) and water-in-oil (W/O)
      emulsions containing the hydrophilic IL [HMIM] [Cl] and the hydrophobic IL [BMIM]
      [PF6] were prepared, and the influence of the ILs on emulsion properties was
      evaluated. It was found that ILs could be successfully incorporated into the
      emulsion structure, resulting in stable formulations. The antimicrobial activity
      of ILs in the formulations was estimated, and their application as preservatives
      was confirmed by performing preservative efficacy tests. Evaluation of the in
      vitro cytotoxicity of the emulsions containing hydrophilic or hydrophobic ILs
      showed the low cytotoxicity of the carriers. Finally, penetration enhancement of
      a fluorescent dye as a model drug in the presence of ionic liquids was shown.

PMID- 23123181
TI  - Real movement vs. motor imagery in healthy subjects.
AB  - Motor imagery tasks are well established procedures in brain computer interfaces,
      but are also used in the assessment of patients with disorders of consciousness.
      For testing awareness in unresponsive patients it is necessary to know the
      natural variance of brain responses to motor imagery in healthy subjects. We
      examined 22 healthy subjects using EEG in three conditions: movement of both
      hands, imagery of the same movement, and an instruction to hold both hands still.
      Single-subject non-parametric statistics were applied to the fast-Fourier
      transformed data. Most effects were found in the alpha- and beta-frequency ranges
      over central electrodes, that is, in the MU-rhythm. We found significant power
      changes in 18 subjects during movement and in 11 subjects during motor imagery.
      In 8 subjects these changes were consistent over both conditions. The significant
      power changes during movement were a decrease of MU-rhythm. There were 2 subjects
      with an increase and 9 subjects with a decrease of MU-rhythm during imagery.
      alpha and beta are the most responsive frequency ranges, but there is a minor
      number of subjects who show a synchronization instead of the more common
      desynchronization during motor imagery. A (de)synchronization of MU-rhythm can be
      considered to be a normal response.

PMID- 23123182
TI  - Syntactic structural parallelisms influence processing of positive stimuli:
      evidence from cross-modal ERP priming.
AB  - Language can strongly influence the emotional state of the recipient. In contrast
      to the broad body of experimental and neuroscientific research on semantic
      information and prosodic speech, the emotional impact of grammatical structure
      has rarely been investigated. One reason for this might be, that measuring
      effects of syntactic structure involves the use of complex stimuli, for which the
      emotional impact of grammar is difficult to isolate. In the present experiment we
      examined the emotional impact of structural parallelisms, that is, repetitions of
      syntactic features, on the emotion-sensitive "late positive potential" (LPP) with
      a cross-modal priming paradigm. Primes were auditory presented nonsense sentences
      which included grammatical-syntactic parallelisms. Visual targets were positive,
      neutral, and negative faces, to be classified as emotional or non-emotional by
      the participants. Electrophysiology revealed diminished LPP amplitudes for
      positive faces following parallel primes. Thus, our findings suggest that
      grammatical structure creates an emotional context that facilitates processing of
      positive emotional information.

PMID- 23123183
TI  - IL-10 promotes production of intestinal mucus by suppressing protein misfolding
      and endoplasmic reticulum stress in goblet cells.
AB  - BACKGROUND & AIMS: Protein misfolding and endoplasmic reticulum (ER) stress have
      been observed in intestinal secretory cells from patients with inflammatory bowel
      diseases and induce intestinal inflammation in mice. However, it is not clear how
      immune factors affect ER stress and therefore disease symptoms. METHODS: We
      analyzed the effects of interleukin (IL)-10 on ER stress in intestinal tissues in
      wild-type C57BL/6, Winnie, IL-10(-/-), and Winnie * IL-10(+/-) mice. In Winnie
      mice, misfolding of the intestinal mucin Muc2 initiates ER stress and
      inflammation. We also analyzed the effects of different inhibitors of IL-10
      signaling and the N-glycosylation inhibitor tunicamycin in cultured human LS174T
      goblet cells. RESULTS: Administration of neutralizing antibodies against IL-10 or
      its receptor (IL-10R1) to Winnie mice rapidly exacerbated ER stress and
      intestinal inflammation compared with mice given vehicle (controls). Antibodies
      against IL-10 also increased accumulation of misfolded Muc2 in the ER of goblet
      cells of Winnie mice and increased T-cell production of inflammatory cytokines.
      Winnie * IL-10(+/-) mice and IL-10(-/-) mice with a single Winnie allele each
      developed more severe inflammation than Winnie mice or IL-10(-/-) mice.
      Administration of tunicamycin to wild-type mice caused intestinal ER stress,
      which increased when IL-10R1 was blocked. In LS174T cells, induction of ER stress
      with tunicamycin and misfolding of MUC2 were reduced by administration of IL-10;
      this reduction required STAT1 and STAT3. In LS174T cells incubated with
      tunicamycin, IL-10 up-regulated genes involved in MUC2 folding and in ER
      associated degradation and maintained correct folding of MUC2, its transport from
      the ER, and its O-glycosylation and secretion. CONCLUSIONS: IL-10 prevents
      protein misfolding and ER stress by maintaining mucin production in goblet cells
      and helps the intestine preserve the mucus barrier.

PMID- 23123184
TI  - Changes in Interleukin-1 alpha serum levels after transplantation of umbilical
      cord blood cells in a model of perinatal hypoxic-ischemic brain damage.
AB  - Transplantation of human umbilical cord blood (hUCB) cells is a potential
      approach for the treatment of perinatal hypoxic-ischemic brain injury.
      Neurological and motor deficits resulting from the brain lesion are ameliorated
      upon transplantation. The molecular mechanisms underlying these improvements are
      currently being unravelled. One parameter identified as part of the beneficial
      effects of hUCB cells is the reduction of brain inflammation. It is, however,
      unclear whether the modulation of brain inflammation is due to local or systemic
      effects of hUCB cells. In this study, the effects of hUCB cell transplantation in
      a model of perinatal hypoxic-ischemic brain injury were investigated at the
      systemic level by measurement of serum levels of pro-inflammatory cytokines by
      multiplex bead arrays. Two days after induction of the brain damage, levels of
      the pro-inflammatory cytokines Interleukin-1alpha (IL-1alpha), Interleukin-1beta
      (IL-1beta), and Tumor necrosis factor alpha (TNFalpha) were increased in the
      serum of rats. Application of hUCB cells, in turn, correlated with a reduced
      elevation of serum levels of these pro-inflammatory cytokines. This decrease was
      accompanied by a reduced expression of CD68, a marker protein of activated
      microglia/macrophages in the brain. Therefore, systemic modulation of the immune
      response by hUCB cells could represent one possible mechanism of how these cells
      might mediate their beneficial effects. Creation of a regenerative environment
      with reduced inflammation might account for the functional regeneration observed
      upon hUCB cell treatment in lesioned animals.

PMID- 23123185
TI  - Metric characterization of the aortic arch of early mouse fetuses and of a fetus
      featuring a double lumen aortic arch malformation.
AB  - This study aimed at providing an objective metric characterization of the aortic
      arch of a mouse fetus featuring a double lumen aortic arch malformation. As a
      side effect it provides reference data defining the length and the diameters of
      the aortic arch segments of normally developed mouse fetuses at developmental
      stage 22 according to Theiler (TS22). We analyzed a total of 22 TS22 mouse
      fetuses of the Him:OF1 strain. We produced high-resolution three-dimensional (3D)
      computer models and measured the diameters and cross sectional areas of the
      aortic arch segments and of the ascending and descending aorta. In addition, we
      defined 3D skeletons of the arteries and measured the length of the aortic arch
      segments. We provide statistics on the measurements obtained from the normally
      developed TS22 fetuses and detailed characterizations of the double lumen aortic
      arch. Our data suggest that: firstly, in Him:OF1 fetuses of TS22, the formation
      of the aortic arch is not yet finished. The left subclavian artery still receives
      a significant amount of blood from the right ventricle. Secondly, persistence of
      the 5th pharyngeal arch artery does not affect remodeling of the arteries distal
      to the junction of 5th pharyngeal arch artery and dorsal aorta. Thirdly,
      hemodynamic forces define the dimensions of the aortic arch between the left
      common carotid and the left subclavian artery. Fourthly, the blood volume
      streaming through the 4th pharyngeal arch artery influences its enlargement
      between TS20 and TS22.

PMID- 23123186
TI  - Ultrasound analyses, anatomical considerations, and clinical experience with the
      peroneus brevis muscle flap.
AB  - This ultrasound study investigated the frequency, location, and diameter of
      segmental blood supply of 34 lower legs in relation to muscle size. Furthermore,
      we investigated the possibilities and constraints of distally pedicled peroneus
      brevis muscle flaps, which allow defect coverage down to the medial as well as
      the lateral ankle. In the proximal part of the peroneus brevis muscle, blood is
      supplied by branches from the anterior tibial artery that perforate the anterior
      intermuscular septum; in the distal part of the muscle, blood is supplied by
      branches from the peroneal artery that perforate the posterior intermuscular
      septum. All lower legs showed at least one perforating vessel penetrating the
      posterior intermuscular septum. In all, 32.4% of the legs showed two perforators
      and 17.6% three perforators. The average position of the most distal perforator
      was 4.8cm proximal to the tip of the malleolus lateralis. Based on this blood
      supply, muscle tissue measuring up to 15-20cm can be harvested and rotated by 180
      degrees  to cover defects of the lower ankle. Our ultrasound study is
      supplemented by an anatomical dissection and two clinical cases of successful
      defect coverage with the distally pedicled peroneus muscle flap.

PMID- 23123187
TI  - Gender differences in anthropometric predictors of physical performance in older
      adults.
AB  - BACKGROUND: Both high body fat and low muscle mass have been associated with
      physical disability in older adults. However, men and women differ markedly in
      body composition; men generally have more absolute and relative lean muscle mass
      and less fat mass than women. It is not known how these anthropometric
      differences differentially affect physical ability in men and women. OBJECTIVES:
      This study examines differences in anthropometric predictors of physical
      performance in older women and men. METHODS: Participants were 470 older women
      and men 72.9 (7.9) years of age. Body composition was measured using dual-energy
      x-ray absorptiometry. Maximum leg strength and power were measured using a leg
      press. Muscle quality (MQ) was calculated as relative strength (leg press
      strength per kilogram of leg muscle mass). Gait speed and chair rise were used to
      assess mobility performance and functional strength. RESULTS: Body mass index
      (BMI), age, and MQ emerged as predictors (P < 0.05) of functional strength and
      mobility in men and women somewhat differently. After accounting for age and
      sample, leg MQ was related to chair rise time and gait speed in men but not
      women. BMI was related to gait speed in both men and women, but BMI was related
      to chair rise time only in women. CONCLUSION: Results implicate the prioritized
      importance of healthy weight and muscle maintenance in older women and men for
      maintained physical functioning with aging.

PMID- 23123189
TI  - The yin of exofacial protein sulfhydryls and the yang of intracellular
      glutathione in in vitro transfection with SS14 bioreducible lipoplexes.
AB  - Although redox-sensitive transfectants have been considered hitherto as the Holy
      Grail of gene delivery because of their ability to restrict the release of
      nucleic acids to intracellular compartments, the reasons for their sometimes
      lackluster performance do not seem likewise clear. To ascertain the possible
      influence of extracellular soluble thiols, exofacial protein sulfhydryls (EPTs)
      and glutathione (GSH) on the overall efficacy of bioreducible lipoplexes, we
      utilized a cationic gemini surfactant--SS14--in which the two single-chain
      amphiphiles are held together by a suitable redox-sensitive linkage. We herein
      draw a big picture whereby the interaction of bioreducible lipoplexes with cells
      and their internalization are tightly coupled events that ultimately do affect
      transfection. Specifically, we provide evidence that EPTs entail the reduction
      triggered disruption of SS14 lipoplexes in plain Dulbecco's Modified Eagle Medium
      (DMEM), thereby resulting in a considerable waste (ca. 30%) of nucleic acids and
      low transgene expression. The DNA release from bioreducible lipoplexes can be
      blunted to ca. 16% by transfecting cells in complete medium and fully reverted by
      preincubating them for 1h before delivery in the same culture supernatant (i.e.
      preconditioning), thus significantly increasing transfection by ca. 3-fold and 10
      fold, respectively. These results lead to the proposal of the protein corona as
      the central mediator in shielding SS14 bioreducible lipoplexes from the action of
      EPTs in the early phase of delivery and provide a smart solution as to how to
      increase their efficacy. Besides, we pinpoint associations between intracellular
      GSH levels and the extent of transfection. All these issues were unique to
      bioreducible lipoplexes.

PMID- 23123188
TI  - Glaucoma therapy by extended release of timolol from nanoparticle loaded silicone
      hydrogel contact lenses.
AB  - Glaucoma is the second major cause of blindness in the world after cataract.
      Glaucoma management through eye drops that reduce the intraocular pressure (IOP)
      has major deficiencies including low patient compliance and low bioavailability.
      Extended wear contact lenses that deliver glaucoma drugs for extended periods
      could increase patient compliance, while also increasing the bioavailability. To
      develop extended wear contact lenses that can also provide extended glaucoma
      therapy, we disperse nanoparticles of PGT (propoxylated glyceryl triacylate) that
      contain a glaucoma drug timolol. The particles can also be loaded into
      prefabricated lenses by soaking the lenses in a solution of particles in ethanol.
      The particle loaded gels can release timolol in phosphate buffered saline (PBS)
      for about a month at room temperature. The most likely rate controlling mechanism
      is hydrolysis of the ester bond that links timolol to the PGT matrix, but other
      mechanisms such as water and drug diffusion, drug dissolution, drug-polymer chain
      cleavage, time-dependent drug permeability within the polymeric matrix, etc. may
      also be important. Nanoparticle incorporation in the silicone hydrogels results
      in reduction in ion and oxygen permeabilities, and an increase in modulus, and
      the impact on each of these properties is proportional to the particle loading. A
      gel with 5% particle loading can deliver timolol at therapeutic doses for about a
      month at room temperature, with a minimal impact on critical lens properties.
      Preliminary animal studies in Beagle dogs conducted with lenses in which
      particles are loaded by soaking the lenses in ethanol show a reduction in IOP.

PMID- 23123190
TI  - Stress-induced nuclear import of apoptosis signal-regulating kinase 1 is mediated
      by karyopherin alpha2/beta1 heterodimer.
AB  - The apoptosis signal-regulating kinase 1 (ASK1) is activated in response to a
      wide variety of extracellular stressors. Consequently, dysregulation of ASK1 is
      associated with multiple pathologies. Here, we show that ASK1 translocates from
      the cytoplasm to the nucleus in HEK293 cells and human cardiomyocytes in response
      to hydrogen peroxide (H(2)O(2)) or angiotensin respectively. Immunoprecipitation
      and mass spectrometry experiments reveal that ASK1 physically interacts with the
      karyopherin alpha2/beta1 heterodimer in response to stress and genetic knockdown
      experiments confirm that this association mediates H(2)O(2)-induced ASK1 nuclear
      translocation. In addition, we have identified a nuclear localization signal
      (NLS)-like motif within the primary amino acid sequence of ASK1 composed of two
      clusters of basic amino acids separated by an intervening 16 amino acid spacer,
      KR[ACANDLLVDEFLKVSS]KKKK. Mutation of the downstream lysine cluster markedly
      reduces the H(2)O(2)-induced ASK1-karyopherin alpha2/beta1 interaction and
      inhibits ASK1 nuclear translocation. Furthermore, we demonstrate that nuclear
      ASK1 is active and participates in H(2)O(2)-induced ASK1-mediated cell death.
      Collectively, our findings have identified a functional interaction between ASK1
      and the karyopherin alpha2/beta1 heterodimer and have also revealed a novel
      mechanism by which nuclear trafficking regulates the apoptotic function of ASK1
      in response to stress.

PMID- 23123191
TI  - Functional interaction of protein kinase CK2 and activating transcription factor
      4 (ATF4), a key player in the cellular stress response.
AB  - Protein kinase CK2 is a pleiotropic enzyme, which is implicated in the regulation
      of numerous biological processes. It seems to regulate the various functions by
      binding to other proteins and by phosphorylation of many different substrates.
      Here, we identified the activating transcription factor 4 (ATF4), an essential
      component of the ER stress signaling, as a new binding partner and a new
      substrate of CK2 in vitro and in vivo. Bifluorescence complementation analysis
      (BiFC) revealed that CK2alpha and ATF4 associate in the nucleus. By using mutants
      of ATF4 we identified serine 215 as the main CK2 phosphorylation site. The ATF4
      S215A mutant turned out to be more stable than the wild-type form. We further
      noticed that an inhibition of CK2 caused an increased transcription of the ATF4
      gene. Analyses of the transcription factor activity revealed an impaired activity
      of the CK2 phosphorylation mutant of ATF4. Thus, we show that (i) ATF4 is a
      binding partner of CK2alpha (ii) ATF4 is a substrate of CK2, (iii) the
      phosphorylation of ATF4 by CK2 influences the stability of ATF4, (iv) the
      transcription of ATF4 is regulated by CK2 and (v) the transcription factor
      activity of ATF4 is regulated by the CK2 phosphorylation of ATF4. Thus, CK2 plays
      an essential role in the regulation of the ER-stress induced signaling pathway.

PMID- 23123192
TI  - Cardiac sodium channel NaV1.5 distribution in myocytes via interacting proteins:
      the multiple pool model.
AB  - The cardiac sodium current (INa) is responsible for the rapid depolarization of
      cardiac cells, thus allowing for their contraction. It is also involved in
      regulating the duration of the cardiac action potential (AP) and propagation of
      the impulse throughout the myocardium. Cardiac INa is generated by the voltage
      gated Na(+) channel, NaV1.5, a 2016-residue protein which forms the pore of the
      channel. Over the past years, hundreds of mutations in SCN5A, the human gene
      coding for NaV1.5, have been linked to many cardiac electrical disorders,
      including the congenital and acquired long QT syndrome, Brugada syndrome,
      conduction slowing, sick sinus syndrome, atrial fibrillation, and dilated
      cardiomyopathy. Similar to many membrane proteins, NaV1.5 has been found to be
      regulated by several interacting proteins. In some cases, these different
      proteins, which reside in distinct membrane compartments (i.e. lateral membrane
      vs. intercalated disks), have been shown to interact with the same regulatory
      domain of NaV1.5, thus suggesting that several pools of NaV1.5 channels may co
      exist in cardiac cells. The aim of this review article is to summarize the recent
      works that demonstrate its interaction with regulatory proteins and illustrate
      the model that the sodium channel NaV1.5 resides in distinct and different pools
      in cardiac cells. This article is part of a Special Issue entitled: Cardiomyocyte
      Biology: Cardiac Pathways of Differentiation, Metabolism and Contraction.

PMID- 23123193
TI  - Biochemical regulation of in vivo function of plant calcium-dependent protein
      kinases (CDPK).
AB  - Calcium (Ca(2+)) is a major second messenger in plant signal transduction
      mediating stress- and developmental processes. Plant Ca(2+)-dependent protein
      kinases (CDPKs) are mono-molecular Ca(2+)-sensor/protein kinase effector
      proteins, which perceive Ca(2+) signals and translate them into protein
      phosphorylation and thus represent an ideal tool for signal transduction. This
      review focuses on recent developments in CDPK structural analysis and CDPK in
      vivo phosphorylation substrate identification. We discuss mechanisms implicated
      in the in vivo regulation of CDPK activity including Ca(2+) binding to the CDPK
      EF-hands, Ca(2+)-triggered intra-molecular conformation changes, and CDPK (auto)
      phosphorylation. Moreover, we address regulation and integration into signaling
      cascades of selected members of the plant CDPK family, for which in vivo function
      and phosphorylation in abiotic and biotic stress signaling have been
      demonstrated. This article is part of a Special Issue entitled: 12th European
      Symposium on Calcium.

PMID- 23123194
TI  - Structure and dynamics of the ATP-bound open conformation of Hsp70 chaperones.
AB  - Central to the chaperone function of Hsp70s is the transition between open and
      closed conformations of their polypeptide substrate binding domain (SBD), which
      is regulated through an allosteric mechanism via ATP binding and hydrolysis in
      their nucleotide binding domain (NBD). Although the structure of the closed
      conformation of Hsp70s is well studied, the open conformation has remained
      elusive. Here, we report on the 2.4 A crystal structure of the ATP-bound open
      conformation of the Escherichia coli Hsp70 homolog DnaK. In the open DnaK
      structure, the beta sheet and alpha-helical lid subdomains of the SBD are
      detached from one another and docked to different faces of the NBD. The contacts
      between the beta sheet subdomain and the NBD reveal the mechanism of allosteric
      regulation. In addition, we demonstrate that docking of the beta sheet and alpha
      helical lid subdomains to the NBD is a sequential process influenced by peptide
      and protein substrates.

PMID- 23123195
TI  - MicroRNAs mediate gene silencing via multiple different pathways in drosophila.
AB  - MicroRNAs (miRNAs) guide RNA-induced silencing complex (RISC) that contains an
      Argonaute family protein to complementary target messenger RNAs (mRNAs). Via
      RISC, miRNAs silence the expression of target mRNAs by shortening the poly(A)
      tail-which leads to mRNA decay-and by repressing translation. It has been
      suggested that GW182, an Argonaute-associating protein, plays the central role in
      such microRNA actions. Here we show that, although GW182 is obligatory for
      poly(A) shortening, translational repression by microRNAs occurs even in the
      absence of GW182. Yet, GW182 is also capable of inducing translational repression
      independently. Both of these translational repression mechanisms block formation
      of 48S and 80S ribosomal complexes. Thus microRNAs utilize at least three
      distinct silencing pathways: GW182-mediated deadenylation and GW182-dependent and
      -independent repression of early translation initiation. Differential
      contribution from these multiple pathways may explain previous, apparently
      contradictory observations of how microRNAs inhibit protein synthesis.

PMID- 23123196
TI  - EGFR-induced and PKCepsilon monoubiquitylation-dependent NF-kappaB activation
      upregulates PKM2 expression and promotes tumorigenesis.
AB  - Many types of human tumor cells have overexpressed pyruvate kinase M2 (PKM2).
      However, the mechanism underlying this increased PKM2 expression remains to be
      defined. We demonstrate here that EGFR activation induces PLCgamma1-dependent
      PKCepsilon monoubiquitylation at Lys321 mediated by RINCK1 ubiquitin ligase.
      Monoubiquitylated PKCepsilon interacts with a ubiquitin-binding domain in NEMO
      zinc finger and recruits the cytosolic IKK complex to the plasma membrane, where
      PKCepsilon phosphorylates IKKbeta at Ser177 and activates IKKbeta. Activated RelA
      interacts with HIF1alpha, which is required for RelA to bind the PKM promoter.
      PKCepsilon- and NF-kappaB-dependent PKM2 upregulation is required for EGFR
      promoted glycolysis and tumorigenesis. In addition, PKM2 expression correlates
      with EGFR and IKKbeta activity in human glioblastoma specimens and with grade of
      glioma malignancy. These findings highlight the distinct regulation of NF-kappaB
      by EGF, in contrast to TNF-alpha, and the importance of the metabolic cooperation
      between the EGFR and NF-kappaB pathways in PKM2 upregulation and tumorigenesis.

PMID- 23123198
TI  - Vocal fold fibroblasts immunoregulate activated macrophage phenotype.
AB  - Recent evidence suggests that fibroblasts play a critical role in regulating
      inflammation during wound healing because they express several inflammatory
      mediators in response to bacteria. The objective of this study was to analyze the
      effects of lipopolysaccharide (LPS) on the immunomodulatory properties of vocal
      fold fibroblasts (VFFs) derived from polyps, scar and normal tissue co-cultured
      with macrophages, to provide insight into their interactions during the
      inflammatory process. Fibroblasts were co-cultured with CD14+ monocytes and after
      7 days, wells were treated with LPS for 24 and 72 h. Culture supernatants were
      collected and concentrations of TNF-alpha, IL-6, IL-8, IL-10, IL-12, IL-1beta and
      MCP-1 were quantified by ELISA. Normal VFF and CD14+ monocultures were used as
      controls. Twenty-four hours after LPS activation, macrophages co-cultured with
      polyp VFF had significantly increased expression of TNF-alpha, IL-1beta, IL-12
      and IL-10 compared to controls (p<0.0001). In contrast, macrophages co-cultured
      with scar VFF had significantly lower expression of TNF-alpha, IL-1beta and IL-12
      with significantly higher IL-10 compared to control (p<0.0001). After 72 h,
      macrophages co-cultured with polyp VFF increased expression of TNF-alpha, IL
      1beta, IL-10, IL-6, IL-8, MCP-1 and TGF-beta (p<0.01) and macrophages co-cultured
      with scar VFF significantly decreased their expression of IL-1beta and IL-12
      compared to control (p<0.0001). Scar VFF at both time points produced
      significantly lower levels of IL-8, MCP-1, IL-6 and TGF-beta compared to controls
      (p<0.05). Based on our findings, VFF and macrophages secrete several inflammatory
      mediators that modify their diverse functions. Polyp and scar VFF may play a role
      in regulating abnormal inflammatory responses, which could result in excessive
      ECM deposition that disrupts the function of the vocal folds.

PMID- 23123197
TI  - Loss of the oxidative stress sensor NPGPx compromises GRP78 chaperone activity
      and induces systemic disease.
AB  - NPGPx is a member of the glutathione peroxidase (GPx) family; however, it lacks
      GPx enzymatic activity due to the absence of a critical selenocysteine residue,
      rendering its function an enigma. Here, we show that NPGPx is a newly identified
      stress sensor that transmits oxidative stress signals by forming the disulfide
      bond between its Cys57 and Cys86 residues. This oxidized form of NPGPx binds to
      glucose-regulated protein (GRP)78 and forms covalent bonding intermediates
      between Cys86 of NPGPx and Cys41/Cys420 of GRP78. Subsequently, the formation of
      the disulfide bond between Cys41 and Cys420 of GRP78 enhances its chaperone
      activity. NPGPx-deficient cells display increased reactive oxygen species,
      accumulated misfolded proteins, and impaired GRP78 chaperone activity. Complete
      loss of NPGPx in animals causes systemic oxidative stress, increases
      carcinogenesis, and shortens life span. These results suggest that NPGPx is
      essential for releasing excessive ER stress by enhancing GRP78 chaperone activity
      to maintain physiological homeostasis.

PMID- 23123201
TI  - Comparison between palpatory findings of the hyoid position and their acoustic,
      videostroboscopic, and perceptual attributes in patients with muscle tension
      dysphonia (with and without organic lesions).
AB  - SUMMARY: The direction in which the hyoid is pulled may change as a result of
      muscle tension dysphonia (MTD). The disposition usually occurs owing to
      paralaryngeal muscular imbalance (decompensation), which can create laryngeal
      dysfunction and consequently deteriorating the voice quality. This study aimed at
      reporting on a comparison between palpatory findings of hyoid position and their
      acoustic and perceptual and stroboscopic attributes among patients with MTD.
      DESIGN: Cross-sectional random triple-blinded study. METHOD: Palpatory, acoustic,
      audioperceptual, and stroboscopic findings of 39 patients with MTD were analyzed
      descriptively and using independent sample t test. RESULTS: Dominant perceptual
      vocal characteristic of patients with pulled-up hyoid position was rough and the
      degrees of jitter and shimmer were higher in patients with pulled-up hyoid
      position than in patients with pulled-down hyoid position (jitter, P=0.019;
      shimmer, P=0.004), whereas signal-to-noise (S/N) ratio was lower in patients with
      pulled-up hyoid position than in pulled-down hyoid patients, but not
      significantly (S/N ratio, P=0.56). The dominant perceptual characteristic of
      patients with pulled-up hyoid position was rough voice, whereas that for pulled
      down hyoid patients was strained voice. On the other hand, the dominant
      observable pattern in patients with pulled-up hyoid was MTD type II (lateral
      constriction), whereas that in patients with pulled-down hyoid was MTD type III
      (moderate anteroposterior constriction). CONCLUSION: There is a general
      congruence between the hyoid pulled direction and its perceptual, acoustic, and
      videostroboscopic findings in patients with MTD.

PMID- 23123199
TI  - Neurobiological markers of exercise-related brain plasticity in older adults.
AB  - The current study examined how a randomized one-year aerobic exercise program for
      healthy older adults would affect serum levels of brain-derived neurotrophic
      factor (BDNF), insulin-like growth factor type 1 (IGF-1), and vascular
      endothelial growth factor (VEGF) - putative markers of exercise-induced benefits
      on brain function. The study also examined whether (a) change in the
      concentration of these growth factors was associated with alterations in
      functional connectivity following exercise, and (b) the extent to which pre
      intervention growth factor levels were associated with training-related changes
      in functional connectivity. In 65 participants (mean age=66.4), we found that
      although there were no group-level changes in growth factors as a function of the
      intervention, increased temporal lobe connectivity between the bilateral
      parahippocampus and the bilateral middle temporal gyrus was associated with
      increased BDNF, IGF-1, and VEGF for an aerobic walking group but not for a non
      aerobic control group, and greater pre-intervention VEGF was associated with
      greater training-related increases in this functional connection. Results are
      consistent with animal models of exercise and the brain, but are the first to
      show in humans that exercise-induced increases in temporal lobe functional
      connectivity are associated with changes in growth factors and may be augmented
      by greater baseline VEGF.

PMID- 23123202
TI  - Affective temperament in women with functional aphonia.
AB  - OBJECTIVES: The aim of the present study was to assess the affective temperament
      in women with functional aphonia. STUDY DESIGN: Cross-sectional. METHODS: Forty
      one women with functional aphonia underwent an examination of affective
      temperament by means of the Temperament Evaluation of Memphis, Pisa and San Diego
      Autoquestionnaire. RESULTS: Compared with the reference group, women with
      functional aphonia show significantly higher rates of depressive and anxious
      temperament. CONCLUSIONS: The results of the present study are concordant with
      the previous findings, indicating elevated levels of depressive and anxious
      symptoms in aphonic patients. Implications for the therapy of functional aphonia
      as well as considerations for further studies are discussed.

PMID- 23123203
TI  - A study of subharmonics in connected speech material.
AB  - Subharmonics are often observed in running speech spectrograms that are difficult
      to quantify. This study investigates the relationship between rough voice quality
      and the presence-and amount-of subharmonics in connected speech material in a
      group of 35 male and 35 female speakers with voice pathology. Spectrum analysis
      was undertaken in 145 pathologic voices, of which 77 had subharmonics in
      connected speech. Only 34% of 70 subjects under investigation developed
      subharmonics in both connected speech and sustained phonations. All voices were
      judged as perceptually rough. The results of this study indicate that male and
      female voices with subharmonics do not differ in examined acoustic
      characteristics except for the modal fundamental frequency (F(0)). A small but
      significant difference in roughness scores between genders seems to be caused by
      the confounding perception of factors not related to acoustic measurements of
      F(0) and number of subharmonics. The degree of roughness has a significant
      relationship with the irregularity index, percentage of low F(0) estimates, and,
      to a lesser extent, power of subharmonics.

PMID- 23123200
TI  - Fluorescent target array T helper assay: a multiplex flow cytometry assay to
      measure antigen-specific CD4+ T cell-mediated B cell help in vivo.
AB  - CD4(+) T cells play a central role in regulating the immune response. Their
      effector function is commonly assessed by their capacity to secrete cytokines
      detected by ELISPOT and intracellular cytokine staining. However, one aspect of
      their effector function that is often overlooked is their ability to help
      activation of cognate B cells directly, a process that is initiated through the
      engagement of their T cell-receptor (TCR) with cognate peptide presented on major
      histocompatibility complex class II (MHC-II) molecules by B cells. Here we report
      a method to monitor CD4(+) T cell-mediated B cell help in vivo using a multiplex
      high throughput assay. This assay utilizes a fluorescent target array (FTA),
      which is composed of lymphocytes labeled with numerous (>200) unique fluorescence
      signatures that can be delineated in a single recipient animal based on
      combination labeling with the three vital dyes carboxyfluorescein diacetate
      succinimidyl ester (CFSE), CellTrace Violet (CTV) and Cell Proliferation Dye
      eFluor 670 (CPD). By pulsing different B cell populations in a FTA with titrated
      amounts of cognate MHC-II binding peptides, CD4(+) T cell help could be assessed
      by measuring induction of the B cell activation markers CD69 and CD44 by antibody
      labeling and flow cytometry. We call this the "FTA T helper assay", and have
      found it to be a robust and sensitive assay to measure CD4(+) T cell helper
      activity across a multitude of peptide-pulsed B "target" cells in real time in
      vivo. Furthermore, the technique can be used simultaneously with the FTA killing
      assay that measures cytotoxic T cell function, to provide a comprehensive tool
      for measuring both CD4(+) and CD8(+) T cell activity during an immune response in
      vivo.

PMID- 23123204
TI  - Altered aquaporins in the brains of mice submitted to intermittent hypoxia model
      of sleep apnea.
AB  - Rostral fluid displacement has been proposed as a pathophysiologic mechanism of
      both central and obstructive sleep apnea. Aquaporins are membrane proteins that
      regulate water transport across the cell membrane and are involved in brain edema
      formation and resolution. The present study investigated the effect of
      intermittent hypoxia (IH), a model of sleep apnea, on brain aquaporins. Mice were
      exposed to intermittent hypoxia to a nadir of 7% oxygen fraction. Brain water
      content, Aquaporin-1 and Aquaporin-3 were measured in the cerebellum and
      hippocampus. Hematoxylin-eosin and immunohistochemistry stainings were performed
      to evaluate cell damage. Compared to the sham group, the hypoxia group presented
      higher brain water content, lower levels of Aquaporin-1 and similar levels of
      Aquaporin-3. Immunoreactivity to GFAP and S100B was stronger in the hypoxia group
      in areas of extensive gliosis, compatible with cytotoxic edema. These findings,
      although preliminary, indicate an effect of IH on aquaporins levels. Further
      investigation about the relevance of these data on the pathophysiology of OSA is
      warranted.

PMID- 23123205
TI  - Relationship between Mecp2 and NFkappab signaling during neural differentiation
      of P19 cells.
AB  - The pluripotent P19 embryo carcinoma cell line was studied to determine a
      signaling pathway regulating MeCP2 expression. P19 cells were induced to
      differentiate into neurons by RA and express beta-III tubulin at one day after
      induction and synaptophysin by 7 days. MeCP2 was first observed after beta-III
      tubulin expression was detected and continued to rise over the course of
      differentiation. Both Mecp2 e1 and e2 mRNA forms progressively increased in
      differentiating cells. MeCP2 expression was increased by tumor necrosis factor
      (TNF) in early differentiating cells, which was blocked by NFkappaB inhibitors.
      TNF did not increase MeCP2 expression in naive cells. Moreover, TNF did not
      increase NFkappaB reporter gene activity in naive cells even though increases
      were observed in early differentiating cells. The protein kinase C activator
      phorbol 12-myristate 13-acetate (PMA) increased MeCP2 expression in naive P19
      cells, which was also blocked by NFkappaB inhibitors. Interestingly, PMA
      increased NFkappaB reporter gene activity in naive cells. Finally, PMA, but not
      TNF, induced IkappaBalpha degradation in naive P19 cells. Taken together, our
      data indicates that MeCP2 expression is regulated in part by signaling pathways
      involving NFkappaB.

PMID- 23123206
TI  - Does conflict control occur without awareness? Evidence from an ERP study.
AB  - The relationship between conflict control and awareness has attracted extensive
      interest. Although researchers have investigated the relationship between
      response conflict and awareness, it still remains unclear whether stimulus
      conflict can occur outside of awareness. In addition, previous studies on the
      role of awareness in conflict control have ignored the fact that conflict control
      includes both conflict detection and resolution. A modified version of the
      flanker task was used to manipulate stimulus and response conflicts under both
      masked and unmasked conditions. The masked condition elicited a sequence of
      distinct event-related potential components that were also observed in the
      unmasked condition. N2 amplitudes presented the following pattern: incongruent
      eligible>incongruent-ineligible>congruent, they did not show any difference under
      the masked and unmasked conditions, suggesting that detection of stimulus-related
      conflict revealed by the comparison between incongruent-ineligible and congruent
      trials, and response-related conflict revealed by the comparison between
      incongruent-eligible and incongruent-ineligible trials can occur in the absence
      of awareness, and unconscious conflict detection might involve the same neural
      network employed for conscious conflict detection. Late positive component (LPC)
      amplitudes also presented as incongruent-eligible>incongruent
      ineligible>congruent at CPz and Pz, irrespective of conscious awareness. However,
      LPC amplitudes under the masked condition were markedly reduced compared to
      unmasked trials. These LPC findings suggest that stimulus- and response-related
      conflict resolution can occur in the absence of awareness; furthermore,
      unconscious conflict resolution might involve a weaker cognitive control network
      compared to conscious conflict resolution. These findings have important
      implications for the theories concerning the relationship between cognitive
      control and awareness.

PMID- 23123207
TI  - Effects of single and repeated electroconvulsive stimulation on hippocampal cell
      proliferation and spontaneous behaviors in the rat.
AB  - Electroconvulsive therapy (ECT) has therapeutic effects on refractory depression
      and schizophrenia, although its biological mechanisms are still unclear. Recent
      studies in rodents suggest that electroconvulsive stimulation-induced seizures
      (ECSs) influence hippocampal adult neurogenesis, which has gained considerable
      traction as a possible cellular substrate for the treatment of depression. The
      aim of this study is to explore alteration of neurogenesis in the hippocampus
      following ECSs and the relationship between neurogenesis and behavior in rats. In
      the present study, we administered a single or 10-repeated application of
      electroconvulsive stimulations that reliably resulted in seizure (an animal model
      of electroconvulsive therapy) to rats. Then cell proliferation of newborn cells
      in the subgranular zone (SGZ) of the dentate gyrus (DG) was investigated 3 and 14
      days after ECS treatments. Cell differentiation was also examined 4 weeks after
      newly formed cells were confirmed. As a result, ECS-induced cell proliferation in
      the hippocampus showed biphasic changes after ECS. The amount of cell
      proliferation at 3 days after the last ECS increased twice as much as the sham
      group. However, the number of proliferating cells at 14 days later decreased to a
      half of the sham level. Differentiation of newly formed cells was not influenced
      in ECS-treated groups compared with sham-treated groups. In addition, we
      investigated the effects of ECS on behavioral changes in rats by measuring
      locomotor activity in an open field test and spontaneous alteration behavior in a
      Y-maze test. Spontaneous behavior and memory function were not influenced by
      repeated ECSs. These results suggest that repeated ECSs affect progenitors that
      have a limited ability for cell proliferation, like amplifying progenitors, to
      increase newly generated neurons without negative behavioral change.

PMID- 23123208
TI  - Ultrastructural and morphometric alterations in the aortic depressor nerve of
      rats due to long term experimental diabetes: effects of insulin treatment.
AB  - Most of the reports about an altered baroreflex attribute this condition to the
      diabetic efferent neuropathy of the aortic depressor nerve (ADN) (afferent arm of
      the baroreflex less explored). We evaluated the ADN ultrastructural alterations
      caused by long term experimental diabetes and the effects of insulin treatment.
      Wistar rats (N=14) received a single intravenous injection of streptozotocin (40
      mg/kg) 12 weeks before the experiment. Control animals (N=9) received vehicle
      (citrate buffer). Insulin treated animals (N=8) received a single subcutaneous
      injection of insulin daily. Under pentobarbital anesthesia the ADNs were isolated
      and had their spontaneous activity recorded. Afterwards, proximal and distal
      segments of the nerves were prepared for transmission electron microscopy study.
      Morphometry of the unmyelinated fibers was carried out with the aid of computer
      software. ADN of the diabetic animals showed axonal atrophy for myelinated
      fibers, with more pronounced alterations of the myelin sheath, such as myelin
      infolding and out folding, presence of myelin balls and very thin myelin sheath
      in relation to the axonal size, particularly for the small myelinated fibers
      becoming evident. No differences were observed in myelinated fiber number and
      their density, as well as on the fascicular area. Unmyelinated fiber number was
      significantly larger in the diabetic group while fiber diameter was significantly
      smaller compared to control. This result suggests axonal atrophy or, if
      associated to the larger number of fibers present in this group, could indicate
      fiber sprouting. These alterations were more evident in the distal segments of
      the nerves and were moderated by insulin treatment.

PMID- 23123209
TI  - Induction of neurite outgrowth in PC12 cells by artemisinin through activation of
      ERK and p38 MAPK signaling pathways.
AB  - Growth of neurite processes is a critical step in neuronal development,
      regeneration, differentiation, and response to injury. The discovery of compounds
      that can stimulate neurite formation would be important for developing new
      therapeutics against both neurodegenerative disorders and trauma-induced neuronal
      injuries. Semisynthetic derivatives of artemisinin, an active compound in
      Artemisia annua, have been effectively used in malaria treatment, but they have
      been shown to possess neurotoxic potential. In this study, we found unexpectedly
      that artemisinin and its derivatives induced neurite outgrowth of PC12 cells.
      Artemisinins containing an endoperoxide bridge such as artemisinin and
      dihydroartemisinin induced growth of neurite processes at concentrations that
      were slightly cytotoxic, artemisinin having the most potent maximal effect among
      them. Deoxyartemisinin, which lacks the endoperoxide bridge, was ineffective.
      Artemisinin-treated cells expressed increased levels of the neuronal marker
      beta(III)-tubulin. Artemisinin upregulated phosphorylation of extracellular
      signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK),
      critical signaling molecules in neuronal differentiation. Consistent with
      activation of the two MAPKs, neurite outgrowth induced by artemisinin was
      inhibited by the MAPK/ERK kinase inhibitor PD98059 and the p38 MAPK inhibitor
      SB203580. Artemisinin also induced phosphorylation of cyclic AMP response element
      binding protein (CREB) that was almost completely attenuated by PD98059 but not
      by SB203580. Taken together, our results indicate that artemisinin and its
      derivatives containing the endoperoxide bridge induced differentiation of PC12
      cells toward a neuronal phenotype and suggest that both activation of ERK
      signaling pathway, which leads to CREB phosphorylation, and activation of p38
      MAPK signaling pathway are involved in this process.

PMID- 23123211
TI  - Lysosome vacuolation disrupts the completion of autophagy during norephedrine
      exposure in SH-SY5Y human neuroblastoma cells.
AB  - In our current study, we examined the mechanism underlying neuronal cell injuries
      caused by norephedrine in SH-SY5Y human neuroblastoma cells. Norephedrine was
      found to induce cytoplasmic vacuolation and a resultant loss of cell viability.
      In the cells treated with norephedrine also, an autophagic marker LC3 was
      converted to its LC3-II activated form, suggesting the induction of autophagy. In
      cells transfected with RFP-LC3 and GFP-LAMP1, a punctate patterning of LC3
      expression and colocalization of LAMP1 with the formed vacuoles were observed,
      highlighting the lysosomal nature of the vacuoles and their association with
      autophagosomes. An autophagic flux assay using tfLC3 (mRFP-GFP-LC3) indicated the
      formation of autophagosomes and autolysosomes by norephedrine stimulation at an
      early timepoint (~3 h). However, at a later timepoint (~6 h), both the dilation
      of autolysosomes/lysosomes and the neutralization of the vacuolar pH were also
      observed. These results thus indicate that norephedrine induces autophagy at an
      early timepoint and cell death with lysosomal dysfunction and autophagy
      disruption at a later timepoint.

PMID- 23123210
TI  - The neuro-behavioral profile in rats after subarachnoid hemorrhage.
AB  - Despite significant advancements in the understanding of the pathophysiological
      mechanisms of subarachnoid hemorrhage (SAH), little is known about the emotional
      consequences. The primary goal of this study was to describe the locomotor and
      behavioral patterns in rats following both a single-injection and double
      injection model of SAH. In 48 rats, SAH was induced by injecting 0.3 ml of
      autologous arterial blood into the cisterna magnum (single-hemorrhagic model). In
      24 of these rats, post-SAH vasospasm was induced by a repeated injection of blood
      into the cisterna magnum 24h later (double-hemorrhagic model). In 24 additional
      rats, 0.3 ml of saline was injected into the cisterna magnum (sham group).
      Neurological performance was assessed at 24, 48 h, 1, 2 and 3 weeks after SAH.
      Four behavioral tests were performed for 3 weeks after SAH for the duration of 6
      consequent days, in the following order: open field test, sucrose preference
      test, elevated plus maze test and forced swimming test. Following both, a single
      and double-hemorrhagic models of SAH, rats were found to have significant
      behavioral abnormalities on the open field test, sucrose preference test,
      elevated plus maze test, and forced swimming test. A more prominent disability
      was found in rats that underwent the double-hemorrhagic model of SAH than rats
      that underwent the single-hemorrhagic model. Both a single and double injection
      model of rats SAH are associated with significant behavioral disturbances
      including locomotor abnormalities, depressive behavior and increased anxiety,
      even as early as 3 weeks after SAH.

PMID- 23123212
TI  - Pregnane X receptor upregulates ABC-transporter Abcg2 and Abcb1 at the blood
      brain barrier.
AB  - ATP-driven efflux transporters are important, selective elements of the blood
      brain barrier. Abcg2 (also brain multidrug resistance protein) and Abcb1 (P
      glycoprotein) belong to the best known ABC-transporters which limit the access of
      therapeutic drugs to the brain and impair pharmacotherapy of central nervous
      system (CNS) disorders. To investigate the question how ATP-binding cassette
      (ABC)-transporters are regulated, we analyzed the influence of the nuclear
      receptor, pregnane X receptor (PXR) on transporter expression. PXR is a
      xenobiotic-activated transcription factor that is highly expressed in barrier
      tissue. Xenobiotics like rifampicin and hyperforin activate PXR and induce Abcb1
      expression. ABC-transporter up-regulation could have potential effects on
      pharmacokinetics of different drugs. To study the influence of PXR on the two
      most prominent efflux transporters we used a primary culture of porcine brain
      capillary endothelial cells (PBCEC) due to higher homologies to the human form of
      PXR. For activation of the pregnane X receptor the ligands hyperforin and
      rifampicin were used. We investigated the effects on the transporters on RNA
      level (quantitative real time PCR), protein level (Western blotting) and
      transport level (uptake assay, active transport). The stimulation of the PBCEC
      with rifampicin or hyperforin showed a significant up-regulation of both ABC
      transporters on RNA level after 6h, whereas an increased protein expression was
      strongest after 12h. Also the transport activity intensified after a period of
      12h for Abcg2 and Abcb1. In conclusion our data prove PXR activation by
      rifampicin and hyperforin lead to an increased ABC-transporter expression and
      transport activity.

PMID- 23123213
TI  - Fine level epitope mapping and conservation analysis of two novel linear B-cell
      epitopes of the avian infectious bronchitis coronavirus nucleocapsid protein.
AB  - The nucleocapsid (N) protein of the infectious bronchitis virus (IBV) may play an
      essential role in the replication and translation of viral RNA. The N protein can
      also induce high titers of cross-reactive antibodies and cell-mediated immunity,
      which protects chickens from acute infection. In this study, we generated two
      monoclonal antibodies (mAbs), designated as 6D10 and 4F10, which were directed
      against the N protein of IBV using the whole viral particles as immunogens. Both
      of the mAbs do not cross react with Newcastle disease virus (NDV), infectious
      laryngotracheitis virus (ILTV) and subtype H9 avian influenza virus (AIV). After
      screening a phage display peptide library and peptide scanning, we identified two
      linear B-cell epitopes that were recognized by the mAbs 6D10 and 4F10, which
      corresponded to the amino acid sequences (242)FGPRTK(247) and
      (195)DLIARAAKI(203), respectively, in the IBV N protein. Alignments of amino acid
      sequences from a large number of IBV isolates indicated that the two epitopes,
      especially (242)FGPRTK(247), were well conserved among IBV strains. This
      conclusion was further confirmed by the relationships of 18 heterologous
      sequences to the 2 mAbs. The novel mAbs and the epitopes identified will be
      useful for developing diagnostic assays for IBV infections.

PMID- 23123214
TI  - The response to interferon is influenced by hepatitis B virus genotype in vitro
      and in vivo.
AB  - PURPOSE: To investigate the effectiveness of an interferon administration on
      different genotypes of hepatitis B virus (HBV) in vitro and in vivo. METHODS: In
      vitro, we transfected plasmids carrying different HBV genotypes including
      recently identified new genotype I into HepG2 and HuH7 cells, then treated with
      standard interferon alpha (IFN-alpha); in vivo, we treated mice with pegylated
      interferon alpha (Peg-IFN-alpha) after injection with HBV DNA of different
      genotypes. The culture supernatants from cell culture and sera from mice were
      collected and used in hepatitis B surface antigen (HBsAg) and hepatitis B e
      antigen (HBeAg) assays by ELISA and HBV DNA measurement by PCR. RESULTS: Both in
      cell culture and in mouse model, it was observed that HBV genotypes A and B
      exhibited significantly better response to IFN-alpha2a or Peg-IFN-alpha2a in
      terms of reduced expression of HBsAg, HBeAg and the HBV DNA level as compared to
      HBV genotypes C and D. Moreover, the inhibitory effect of IFN-alpha2a or Peg-IFN
      alpha2a on HBV genotype I was greater than on genotype C or D, but less than
      genotype A. However, there was no significant response difference between
      genotypes A and B, C and D, B and I, respectively. CONCLUSION: The effectiveness
      of IFN/Peg-IFN to suppress HBV replication is dependent on different HBV
      genotypes. IFN/Peg-IFN is more effective on HBV genotype A or B than on genotype
      C, D or I. Treatment regimens are suggested to be adapted to HBV genotype.

PMID- 23123216
TI  - Rice yellow mottle virus in Madagascar and in the Zanzibar Archipelago; island
      systems and evolutionary time scale to study virus emergence.
AB  - Rice yellow mottle virus (RYMV), of the genus Sobemovirus, is a major threat to
      rice cultivation in Africa. Long range transmission of RYMV, difficult to study
      experimentally, is inferred from a detailed analysis of the molecular diversity
      of the virus in Madagascar and in the Zanzibar Archipelago (Zanzibar and Pemba
      Islands; Tanzania) compared with that found elsewhere in Africa. A unique
      successful introduction of RYMV to Madagascar, which is ca. 400 km from mainland
      Africa, contrasted with recurrent introductions of the virus to the Zanzibar
      Archipelago, ca. 40 km from the East African coast. Accordingly, RYMV dispersal
      over distances of hundreds of kilometers is rare whereas spread of the virus over
      distances of tens of kilometers is relatively frequent. The dates of introduction
      of RYMV to Madagascar and to Pemba Island were estimated from three sets of ORF4
      sequences of virus isolates collected between 1966 and 2011. They were compared
      with the dates of the first field detection in Madagascar (1989) and in Pemba
      Island (1990). The estimates did not depend substantially on the data set used or
      on the evolutionary model applied and their credible intervals were narrow. The
      estimated dates are recent - 1978 (1969-1986) and 1985 (1977-1993) in Madagascar
      and in Pemba Island, respectively - compared to the early diversification of RYMV
      in East Africa ca. 200 years ago. They predated by 5-10 years the first field
      detections in these islands. The interplay between virus sources, rice
      cultivation and long range dispersal which led to RYMV emergence and spread is
      enlightened.

PMID- 23123215
TI  - Evaluation of the enhancing ability of three adjuvants for DNA vaccination using
      the porcine circovirus type 2 ORF2 (capsid) gene in mice.
AB  - Molecular adjuvants were used to augment the amplitude of the immune response in
      many studies recently. Ubiquitin (ub), the peptide binding truncated C-terminal
      portion of heat shock protein 70 (hsp70c) and interleukin-2 (IL-2) are widely
      investigated adjuvants which have been proved to be efficient. In our study, we
      compared the enhancing ability of these three adjuvants based on DNA vaccination
      using the porcine circovirus type 2 ORF2 (capsid) gene in mice. The results of
      lymphocyte proliferation assay, flow cytometric analysis (FCM), antibody titer
      and cytokine production showed that ub conjugated plasmid induced a stronger Th1
      type cellular immune response and an observably higher level of Cap-specific
      serum immunoglobulin G antibody compared with hsp70c or IL-2 conjugated plasmids
      during the period of post-immunization. Meanwhile, the ub conjugation vaccinated
      group elicited stronger specific immunity against PCV2 challenge than the others
      during most of the time of post-challenge. Thus, these data indicate that ub is a
      superior adjuvant for a PCV2 DNA vaccination than the hsp70c and IL-2 molecules.

PMID- 23123217
TI  - Adenylyl cyclase 6 enhances NKCC2 expression and mediates vasopressin-induced
      phosphorylation of NKCC2 and NCC.
AB  - Arginine vasopressin (AVP) affects kidney function via vasopressin V2 receptors
      that are linked to activation of adenylyl cyclase (AC) and an increase in cyclic
      adenosine monophosphate formation. AVP/cyclic adenosine monophosphate enhance the
      phosphorylation of the Na-K-2Cl cotransporter (NKCC2) at serine residue 126
      (pS126 NKCC2) and of the Na-Cl cotransporter (NCC) at threonine 58 (pT58 NCC).
      The isoform(s) of AC involved in these responses, however, were unknown.
      Phosphorylation of S126 NKCC2 and T58 NCC, induced by the V2 receptor agonist (1
      desamino-8-D-arginine vasopressin) in wild-type mice, is lacking in knockout mice
      for AC isoform 6 (AC6). With regard to NKCC2 phosphorylation, the stimulatory
      effect of 1-desamino-8-D-AVP and the defect in AC6(-/-) mice seem to be
      restricted to the medullary portion of the thick ascending limb. AC6 is also a
      stimulator of total renal NKCC2 protein abundance in medullary and cortical thick
      ascending limb. Consequently, mice lacking AC6 have lower NKCC2 expression and a
      mild Bartter syndrome-like phenotype, including lower plasma concentrations of K+
      and H+ and compensatory upregulation of NCC. Increased AC6-independent
      phosphorylation of NKCC2 at S126 might help to stabilize NKCC2 activity in the
      absence of AC6. Renal AC6 determines total NKCC2 expression and mediates
      vasopressin-induced NKCC2/NCC phosphorylation. These regulatory mechanisms, which
      are defective in AC knockout mice, are likely responsible for the observed mild
      Bartter syndrome.

PMID- 23123218
TI  - Hospitalization and psychosis: influences on the course of cognition and everyday
      functioning in people with schizophrenia.
AB  - Long term institutional stay has decreased markedly in people with schizophrenia,
      although there are still many individuals with a history of long-term
      institutional stay residing in the community. In addition, although the average
      duration of acute admissions for schizophrenia is also decreasing, there are
      indications that psychotic episodes leading to acute admissions are associated
      with risk for cognitive and functional declines and changes in brain structure.
      In this paper we review the literature on cognitive changes with aging and
      institutionalization in schizophrenia, reaching to the conclusion that the
      reasons for current chronic institutionalization largely include severe psychosis
      and aggressive behavior. Thus, these factors may be the operative factor in the
      age-related declines in cognition and functioning reported in this population. We
      also present evidence to suggest that these changes may be similar to those seen
      in younger patients who experience repeated psychotic episodes leading to
      hospitalization. Our conclusion is that there is minimal evidence that
      hospitalization, long or short, leads to cognitive and functional changes, but
      rather that the reason for these hospitalizations may underlie cognitive and
      functional declines. Prevention of relapse and discovering treatments to assist
      patients with resistant symptoms may reduce the risk of cognitive and functional
      declines across the lifespan in people with schizophrenia.

PMID- 23123219
TI  - Noise-induced changes in cochlear compression in the rat as indexed by forward
      masking of the auditory brainstem response.
AB  - The current study was undertaken to investigate changes in forward masking
      patterns using on-frequency and off-frequency maskers of 7 and 10 kHz probes in
      the Sprague-Dawley rat. Off-frequency forward masking growth functions have been
      shown in humans to be non-linear, while on-frequency functions behave linearly.
      The non-linear nature of the off-frequency functions is attributable to active
      processing from the outer hair cells, and was therefore expected to be sensitive
      to noise-induced cochlear damage. For the study, nine Sprague-Dawley rats'
      auditory brainstem responses (ABRs) were recorded with and without forward
      maskers. Forward masker-induced changes in latency and amplitude of the initial
      positive peak of the rats' auditory brainstem responses were assessed with both
      off-frequency and on-frequency maskers. The rats were then exposed to a noise
      designed to induce 20-40 dB of permanent threshold shift. Twenty-one days after
      the noise exposure, the forward masking growth functions were measured to assess
      noise-induced changes in the off-frequency and on-frequency forward masking
      patterns. Pre-exposure results showed compressive non-linear masking effects of
      the off-frequency conditions on both latency and amplitude of the auditory
      brainstem response. The noise rendered the off-frequency forward masking patterns
      more linear, consistent with human behavioral findings. On- and off-frequency
      forward masking growth functions were calculated, and they displayed patterns
      consistent with human behavioral functions, both prior to noise and after the
      noise exposure.

PMID- 23123220
TI  - Characteristics and clinical applications of ocular vestibular evoked myogenic
      potentials.
AB  - Recently, ocular vestibular evoked myogenic potentials (oVEMPs) have been
      described and added to the neuro-otologic test battery as a new measure for the
      vestibulo-ocular reflex. oVEMPs represent extraocular muscle activity in response
      to otolith stimulation e.g. by air-conducted sound or bone-conducted vibration.
      In response to vestibular stimulation, electromyographic activity of the
      extraocular muscles can be recorded by means of surface electrodes placed beneath
      the contralateral eye. oVEMPs are likely to reflect predominantly utricular
      function, while the widely established cervical vestibular evoked myogenic
      potentials (cVEMPs) assess saccular function. Thus, measuring oVEMPs and cVEMPs
      in addition to caloric and head impulse testing provides further evaluation of
      the vestibular system and enables quick and cost-effective assessment of otolith
      function. This review summarizes the neurophysiological properties of oVEMPs,
      gives recommendations for recording conditions and discusses oVEMP alterations in
      various disorders of the vestibular system. With increasing insight into oVEMP
      characteristics in vestibular disorders, e.g. Meniere's disease and superior
      semicircular canal dehiscence syndrome, oVEMPs are becoming a promising new
      diagnostic tool for evaluating utricular function.

PMID- 23123221
TI  - Effect of nucleos(t)ide analogue therapy on hepatocarcinogenesis in chronic
      hepatitis B patients: a propensity score analysis.
AB  - BACKGROUND & AIMS: Some patients with chronic hepatitis B virus (HBV) infection
      progress to hepatocellular carcinoma (HCC). However, the long-term effect of
      nucleos(t)ide analogue (NA) therapy on progression to HCC is unclear. METHODS:
      Therefore, we compared chronic hepatitis B patients who received NA therapy to
      those who did not, using a propensity analysis. RESULTS: Of 785 consecutive HBV
      carriers between 1998 and 2008, 117 patients who received NA therapy and 117
      patients who did not, were selected by eligibility criteria and propensity score
      matching. Factors associated with the development of HCC were analyzed. In the
      follow-up period, HCC developed in 57 of 234 patients (24.4%). Factors
      significantly associated with the incidence of HCC, as determined by Cox
      proportional hazards models, include higher age (hazard ratio, 4.36 [95%
      confidence interval, 1.33-14.29], p=0.015), NA treatment (0.28 [0.13-0.62],
      p=0.002), basal core promoter (BCP) mutations (12.74 [1.74-93.11], p=0.012), high
      HBV core-related antigen (HBcrAg) (2.77 [1.07-7.17], p=0.036), and high gamma
      glutamyl transpeptidase levels (2.76 [1.49-5.12], p=0.001). CONCLUSIONS: NA
      therapy reduced the risk of HCC compared with untreated controls. Higher serum
      levels of HBcrAg and BCP mutations are associated with progression to HCC,
      independent of NA therapy.

PMID- 23123222
TI  - Marriage and motherhood are associated with lower testosterone concentrations in
      women.
AB  - Testosterone has been hypothesized to modulate the trade-off between mating and
      parenting effort in males. Indeed, evidence from humans and other pair-bonded
      species suggests that fathers and men in committed relationships have lower
      testosterone levels than single men and men with no children. To date, only one
      published study has examined testosterone in relation to motherhood, finding that
      mothers of young children have lower testosterone than non-mothers. Here, we
      examine this question in 195 reproductive-age Norwegian women. Testosterone was
      measured in morning serum samples taken during the early follicular phase of the
      menstrual cycle, and marital and maternal status were assessed by questionnaire.
      Mothers of young children (age <=3) had 14% lower testosterone than childless
      women and 19% lower testosterone than women who only had children over age 3.
      Among mothers, age of the youngest child strongly predicted testosterone levels.
      There was a trend towards lower testosterone among married women compared to
      unmarried women. All analyses controlled for body mass index (BMI), age, type of
      testosterone assay, and time of serum sample collection. This is the first study
      to look at testosterone concentrations in relation to marriage and motherhood in
      Western women, and it suggests that testosterone may differ with marital and
      maternal status in women, providing further corroboration of previous findings in
      both sexes.

PMID- 23123224
TI  - Comparison the neuropreotective effect of Cortex Phellodendri chinensis and
      Cortex Phellodendri amurensis against beta-amyloid-induced neurotoxicity in PC12
      cells.
AB  - Cortex Phellodendron chinensis (CPC) and Cortex Phellodendron amurensis (CPA)
      derived from the dried bark of Phellodendron chinense Schneid. or Phellodendron
      amurense Rupr., respectively, are used interchangeably in clinical practice under
      the name "Huang Bai" for centuries in Chinese medicine for the treatment of
      various inflammatory conditions. Previous study in our laboratory demonstrated
      that CPC and CPA had different anti-diarrheal, anti-bacterial and anti
      inflammatory effects. In this present study, we aimed to compare the protective
      effect of ethanol extract of Cortex Phellodendri chinensis (ECPC) and Cortex
      Phellodendri Amurensis (ECPA) against beta-amyloid (Abeta)-induced neurotoxicity
      in PC12 cells, a typical model of Alzheimer's disease. The results showed that
      ECPC and ECPA contain four common chemical markers such as berberine, but
      palmatine and jatrorrhizin were not found in CPC in contrast to the presence in
      CPA. In addition, both ECPC and ECPA can significantly increase the cell
      viability in Abeta-treated PC12 cells. Moreover, ECPC and ECPA can markedly
      elevate the ratio of the protein and mRNA levels of Bcl-2/Bax, while remarkably
      decrease the release of cytochrome c, and the protein and mRNA expression of
      caspase-3. Interestingly, ECPA has better protective effect than ECPC against
      Abeta-induced neurotoxicity in PC12 cells. These results indicate that both ECPC
      and ECPA have potential protective effect against Abeta-induced neurotoxicity in
      PC12 cells, and ECPA is more potential of the two species to be used in
      traditional medicine as a neuroprotective agent for the treatment of AD. The
      neuroprotective effect of the two species may be mediated, at least in part, via
      suppressing of the cellular apoptosis.

PMID- 23123225
TI  - beta-Asarone, an active principle of Acorus calamus rhizome, inhibits
      morphogenesis, biofilm formation and ergosterol biosynthesis in Candida albicans.
AB  - Anti-Candida potential of Acorus calamus rhizome and its active principle, beta
      asarone, was evaluated against the human fungal pathogen, Candida albicans. beta
      Asarone exhibited promising growth inhibitory activity at 0.5mg/ml and it was
      fungicidal at 8 mg/ml. Time dependant kill curve assay showed that MFC of beta
      asarone was highly toxic to C. albicans, killing 99.9% inoculum within 120 min of
      exposure. beta-Asarone caused significant inhibition of C. albicans morphogenesis
      and biofilm development at sub-inhibitory concentrations. Our data indicate that
      the growth inhibitory activity of beta-asarone might be through inhibition of
      ergosterol biosynthesis. Hemolytic assay showed that beta-asarone is non-toxic,
      even at concentrations approaching MIC value. Our results suggest that beta
      asarone may be safe as a topical antifungal agent.

PMID- 23123223
TI  - Preparation of Galipea officinalis Hancock type tetrahydroquinoline alkaloid
      analogues as anti-tumour agents.
AB  - The preparation of chiral tetrahydroquinolines using Ir-catalysed asymmetric
      hydrogenation and their possible cytotoxic potential anti-cancer activity were
      reported. Both of the in vitro cytotoxicity assay on a series of human cancer
      cell lines including A549 small cell lung cancer, MDA-MB-231 breast cancer, SaoS2
      sacroma, SKHep-1 hepatoma and Hep3B hepatocellular carcinoma as well as in vivo
      animal model using Hep3B hepatocellular tumour xenograft on athymic nude mice
      suggest that 1,2,3,4-tetrahydroquin-8-ol is a potential anti-tumour alkaloid
      which may be further developed as a novel cancer chemotherapeutic agent.

PMID- 23123226
TI  - The Chinese Pueraria root extract (Pueraria lobata) ameliorates impaired glucose
      and lipid metabolism in obese mice.
AB  - The incidence of type 2 diabetes and metabolic disease is rapidly increasing, but
      effective therapies for their prevention and treatment have been poorly tolerated
      or minimally effective. In this study, chronic administration of kudzu root
      extract (8 months, 0.2%, w/w, in diet) decreased baseline fasting plasma glucose
      (183+/-14 vs. 148+/-11 mg/dl) and improved glucose and insulin tolerance in
      C57BL/6J ob/ob mice (1.67+/-0.17 ng/ml [kudzu treated] vs. 2.35+/-0.63 ng/ml
      [control]), but such treatment did not alter these parameters in lean control
      mice. Among the mice on the kudzu supplementation, plasma levels of isoflavone
      metabolites were significantly higher in ob/ob versus lean control mice, and
      unmetabolized puerarin (11.50+/-5.63 ng/g) was found in adipose tissue only in
      the treated mice. Together, these data demonstrate that a puerarin containing
      kudzu diet improves glucose and insulin responsiveness in ob/ob mice, suggesting
      that puerarin may be a beneficial adjuvant for treating metabolic disease.

PMID- 23123228
TI  - Predictors of progression to severe Alzheimer's disease in an incidence sample.
AB  - BACKGROUND: Little is known about factors influencing time to severe Alzheimer's
      disease (AD). METHODS: Incident cases of AD in the cache county memory study were
      identified. Severe AD was defined as mini-mental state examination score of <=10
      or Clinical Dementia Rating Scale score of 3; cases with either mini-mental state
      examination score of >=16 or clinical dementia rating <2 were not categorized as
      severe AD. Kaplan-Meier, log-rank tests, and Cox analyses were used to identify
      demographic, clinical, and genetic correlates of time to progression to severe
      AD. RESULTS: Sixty-eight of 335 cases of incident AD developed severe dementia.
      In bivariate analyses, female gender, less than high school education, at least
      one clinically significant Neuropsychiatric Inventory domain at baseline, and the
      youngest and oldest ages exhibited shorter time to severe AD. In competing risk
      analysis, subjects with mild or at least one clinically significant
      neuropsychiatric inventory domain score, and subjects with worse health were more
      likely to progress to severe dementia or death. CONCLUSIONS: Demographic and
      clinical variables predict progression to severe AD. Further study should examine
      whether these relationships are causal or correlational.

PMID- 23123229
TI  - Predictors and outcomes for caregivers of people with mild cognitive impairment:
      a systematic literature review.
AB  - BACKGROUND: Dementia caregiving is strongly linked to depression, anxiety, and
      burden in caregivers. Little is known about whether the same holds for people
      supporting an older person with mild cognitive impairment (MCI). We aim to
      systematically review the current evidence for negative caregiver outcomes in MCI
      using Pearlin and colleagues' stress process model as a theoretical framework.
      METHODS: Widely used scientific literature databases were searched using MCI- and
      caregiver-related terms with "AND" relations. Results were limited to
      quantitative English language articles published in peer-reviewed journals
      between 1980 and November 2010. RESULTS: Of the 266 identified articles, six
      reported relevant depression data on 988 MCI caregivers (73% spouses). The pooled
      Center for Epidemiologic Studies Depression scale (CES-D) mean score was 12.95
      (standard deviation = 6.16). The pooled depression prevalence (i.e., CES-D score
      >= 16 or equivalent) was 23%. Two studies compared depression in MCI and dementia
      caregivers, indicating higher levels in dementia caregivers. Other outcomes, such
      as burden, stress, or anxiety, were only investigated by individual studies
      precluding pooling of data. Similarly, pooling of the data on the predictors of
      caregiver outcomes was impossible because of data heterogeneity. However,
      descriptive analysis of predictors revealed that Pearlin and colleagues'
      caregiver stress process model at least partially applies to the MCI context.
      CONCLUSIONS: The studies reviewed were all cross sectional in design, involving
      clinical samples, thus limiting generalizability. Depression and psychological
      comorbidity, although not as pronounced as in dementia caregivers, are common
      complications in MCI caregivers. The long-term course of outcomes in MCI
      caregivers requires further investigation.

PMID- 23123227
TI  - Apolipoprotein E genotype, dementia, and mortality in the oldest old: the 90+
      Study.
AB  - BACKGROUND: Although the apolipoprotein E (APOE) epsilon4 allele is a major
      genetic risk factor for Alzheimer's disease (AD), it is not clear whether this
      relationship persists among the oldest old. Several European studies suggest that
      the effect of the APOE epsilon4 allele on dementia and mortality disappears in
      very old age. We describe the APOE allele and genotype frequencies and examine
      whether the presence of the APOE epsilon4 or APOE epsilon2 alleles is related to
      prevalent dementia, incident dementia, and mortality in a population-based cohort
      of oldest-old participants in the United States. METHODS: We studied 904
      participants aged 90 years and older from The 90+ Study. Eight hundred two (89%)
      participants were genotyped and included in the prevalent dementia and mortality
      analyses. The 520 initially nondemented participants were included in the
      incident dementia analyses and were evaluated for dementia every 6 months.
      RESULTS: The APOE epsilon4 allele was significantly associated with prevalent
      dementia (odds ratio = 2.06) and AD (odds ratio = 2.37) in women but not in men.
      The APOE epsilon2 allele was not related to prevalent dementia in either sex.
      After an average follow-up of 2.4 years, 188 incident dementia cases were
      identified. Neither the APOE epsilon4 nor the APOE epsilon2 allele was related to
      incident dementia or AD. Five hundred ten (64%) participants died after an
      average follow-up of 2.3 years, and their mortality was not related to the
      presence of either the APOE epsilon2 or APOE epsilon4 allele. CONCLUSIONS: Our
      findings suggest that the associations between APOE epsilon4, dementia, and
      mortality are age dependent, and that APOE epsilon4 no longer plays a role in
      dementia and mortality at very old ages.

PMID- 23123230
TI  - Hierarchical Bayesian cognitive processing models to analyze clinical trial data.
AB  - Identifying disease-modifying treatment effects in earlier stages of Alzheimer's
      disease (AD)-when changes are subtle-will require improved trial design and more
      sensitive analytical methods. We applied hierarchical Bayesian analysis with
      cognitive processing (HBCP) models to the Alzheimer's Disease Assessment Scale
      Cognitive subscale (ADAS-Cog) and MCI (mild cognitive impairment) Screen word
      list memory task data from 14 Alzheimer's disease AD patients of the Myriad
      Pharmaceuticals' phase III clinical trial of Flurizan (a gamma-secretase
      modulator) versus placebo. The original analysis of 1649 patients found no
      treatment group differences. HBCP analysis and the original ADAS-Cog analysis
      were performed on the small sample. HBCP analysis detected impaired memory
      storage during delayed recall, whereas the original ADAS-Cog analytical method
      did not. The HBCP model identified a harmful treatment effect in a small sample,
      which has been independently confirmed from the results of other gamma-secretase
      inhibitor. The original analytical method applied to the ADAS-Cog data did not
      detect this harmful treatment effect on either the full or the small sample.
      These findings suggest that HBCP models can detect treatment effects more
      sensitively than currently used analytical methods required by the Food and Drug
      Administration, and they do so using small patient samples. 

PMID- 23123231
TI  - A prediction model to calculate probability of Alzheimer's disease using
      cerebrospinal fluid biomarkers.
AB  - BACKGROUND: We aimed to develop a prediction model based on cerebrospinal fluid
      (CSF) biomarkers, that would yield a single estimate representing the probability
      that dementia in a memory clinic patient is due to Alzheimer's disease (AD).
      METHODS: All patients suspected of dementia in whom the CSF biomarkers had been
      analyzed were selected from a memory clinic database. Clinical diagnosis was AD
      (n = 272) or non-AD (n = 289). The prediction model was developed with logistic
      regression analysis and included CSF amyloid beta42, CSF phosphorylated tau181,
      and sex. Validation was performed on an independent data set from another memory
      clinic, containing 334 AD and 157 non-AD patients. RESULTS: The prediction model
      estimated the probability that AD is present as follows: p(AD) = 1/(1 + e (- [
      0.3315 + score])), where score is calculated from -1.9486 * ln(amyloid beta42) +
      2.7915 * ln(phosphorylated tau181) + 0.9178 * sex (male = 0, female = 1). When
      applied to the validation data set, the discriminative ability of the model was
      very good (area under the receiver operating characteristic curve: 0.85). The
      agreement between the probability of AD predicted by the model and the observed
      frequency of AD diagnoses was very good after taking into account the difference
      in AD prevalence between the two memory clinics. CONCLUSIONS: We developed a
      prediction model that can accurately predict the probability of AD in a memory
      clinic population suspected of dementia based on CSF amyloid beta42, CSF
      phosphorylated tau181, and sex.

PMID- 23123232
TI  - [Uterine rupture: prediction, diagnosis et management].
AB  - OBJECTIVES: To evaluate predictors of uterine rupture (UR) after previous
      cesarean birth. To define the diagnosic criteria of UR, management and prognosis
      of subsequent pregnancies. MATERIALS AND METHODS: Analysis of Medline
      database((r)), Cochrane Library Database((r)) and international guidelines.
      RESULTS: Uterine rupture is a serious complication both for mother (mortality<1
      %, severe morbidity 15 %) and child (mortality at term 3-6%, perinatal asphyxia 6
      15%), occurring in 0,2 to 0,8 % of trial of labour after cesarean (TOLAC). The
      individual risk for UR after TOLAC is multifactorial and predictive scores showed
      no clinical utility in routine (grade B). The risk of UR is decreased in case of
      previous vaginal delivery and increased in case of classical C-section, previous
      UR, induction of labour (especially using prostaglandins), more than one previous
      caesarean section, fetal macrosomia and interval less than 6 months before the
      next pregnancy. Monitoring of labor, including intrauterine pressure catheters,
      do not allow to anticipate the diagnosis. This one relies on a combination of
      severe pathologic patterns of FHM with unusual pelvic pain. Suspected UR requires
      expedited laparotomy (consensus opinion). A subsequent pregnancy is not
      contraindicated, but the risk of recurrent UR is high and a repeat cesarean
      section is then recommended (grade B).

PMID- 23123233
TI  - GLP-compliant evaluation and standardization of the peripubertal castrate male
      rat Hershberger assay for oral exposure of test agents.
AB  - Since oral exposure is more relevant than the sc route for human exposure to
      environmental substances, studies to evaluate and standardize this route in the
      Hershberger assay were conducted in 2001-2003. Interest in environmental androgen
      agonists is increasing, so the oral route of the Hershberger assay may be useful
      to quantify agonist activity of these substances. Castrated Sprague-Dawley rats
      were dosed (PND 60-69) with androgen receptor agonists and/or antagonists,
      terminated on PND 70, and body, liver, and accessory sex organs (ASOs) weighed.
      Methyltestosterone (MT) po, at 0.1-50mg/kg/day, resulted in dose-dependent
      increases in ASO weights at 5-50 mg/kg; 0.1 mg/kg/day was without statistically
      significant effect. Testosterone propionate (TP) (sc) at 0.1-1.6 mg/kg/day also
      resulted in dose-dependent increases in ASO weights, at all doses. Detection of
      putative androgen antagonists by the oral route was confirmed with dose-response
      curves of antagonism from flutamide (FLU) po at 1, 5, or 10 mg/kg/day, with MT at
      5 or 10 mg/kg/day (po, 4h later). These results extend the OECD Hershberger assay
      evaluation and standardization to the oral route and identify and discuss
      challenges of the assay to detect (anti)androgen-active compounds.

PMID- 23123234
TI  - [Anterior traumatic axial disruption of the middle carpal joint. Case report with
      literature review].
AB  - We report a case of traumatic axial disruption of the radial mid carpal joint.
      This unusual type of scaphotrapezo-trapezoidal dislocation occurred after falling
      from a height. We performed open reduction and wire fixation. At 12months follow
      up, functional outcome was satisfactory with good muscle strength (clamping
      force, grip strength and pinch grip: 90% compared to the opposite side) and good
      range of motion was preserved. Work was resumed at the tenth week. Radial
      midcarpal disruption is uncommon. It includes the separation of the trapezium,
      trapezoidal, first and second and third metacarpal bones from the remaining
      wrist. This pattern of carpal derangement has not been previously described in
      the literature. Mechanism of the injury and treatment are discussed.

PMID- 23123235
TI  - Theoretical studies on structures and electronic spectra of linear free radicals
      CnH (n=5-12).
AB  - The B3LYP, CAM-B3LYP, and coupled cluster CCSD(T) calculations have been utilized
      to determine the equilibrium structures of linear carbon radicals CnH (n=5-12) in
      their ground states, as well as the CASSCF method used to optimize the ground and
      selected low-lying excited states. DFT-calculations show that even-n radicals
      C2nH have polyacetylene-like structures with significant single-triple bond
      length alternation, whereas the odd-numbered analogues C2n+1H exhibit a trend
      from polyacetylene-like characters into cumulenic-like arrangement towards C ends
      along the carbon chains. The stabilities of the system under study have been
      evaluated by analyses of the vibrational frequencies and incremental binding
      energies. For the whole CnH (n=5-12) series, the vertical excitation energies and
      oscillator strengths have been calculated at the CASPT2/cc-pVTZ level of theory.
      At the B3LYP optimized geometries, the lowest 1(2)Delta<-X2Pi transitions for C5H
      and C7H occur at 2.36 and 2.14 eV, respectively, comparing well with the observed
      values of 2.33 and 2.09 eV. Moreover, the strongest 2(2)Pi<-X2Pi transitions for
      C2nH (n=3-6) are predicted to be at 2.39, 2.00, 1.80, and 1.64 eV, respectively,
      which are in agreement with the experimental observations. Additionally, the
      possible dissociation channels and the fragmentation energies of CnH (n=5-12)
      series are discussed in the paper.

PMID- 23123236
TI  - Efficient combination of promoter and catalyst for chromic acid oxidation of
      propan-2-ol to acetone in aqueous acid media at room temperature.
AB  - Oxidation of propan-2-ol to acetone was carried out in aqueous media at room
      temperature. The effect of promoter (PA, bpy, phen), micellar catalyst (SDS, CPC,
      TX-100) and their combination has been studied. The reactions were performed
      under the condition [Propan-2-ol]T?[Cr(VI)]T at 30 degrees C. Then kobs and half
      life of all the reaction were determined to identify which promoter and which
      combination are the most effective for this oxidation. Among the promoters phen
      accelerates the reaction most in aqueous media. In absence of promoters anionic
      surfactant SDS increases the rate more effectively than neutral surfactant TX
      100. CPC retards the rate in comparison to aqueous media. The rate of the
      oxidation is highest in presence of the combination of bpy and SDS.

PMID- 23123237
TI  - The effect of poly(vinyl alcohol) on the photophysical properties of pyronin dyes
      in aqueous solution: a spectroscopic study.
AB  - The photophysical properties of pyronin B (PyB) and pyronin Y (PyY) in water and
      poly(vinyl alcohol) (PVA) aqueous solutions were studied by using absorption,
      steady-state fluorescence and time-resolved fluorescence spectroscopy techniques
      at room temperature. The spectroscopic and photophysical properties of pyronin
      dyes in the concentrated PVA aqueous solution were different than those found in
      water. The aggregation of the pyronin dyes in the concentrated PVA aqueous
      solution was prevented with ease while the dye aggregation was generally formed
      in water with high dye concentration. The decrease in the aggregation tendency of
      pyronin dyes in the concentrated PVA aqueous solution caused an increase in
      radiative transitions. The addition of PVA into the aqueous solution induced the
      enhancement in the fluorescence intensity of the dyes compared to those in water.
      As a result, the quantum yields of the dyes were improved by the addition of PVA
      at high loading. The time-resolved fluorescence study revealed that the
      fluorescence decay of dyes in all solutions were found to be single-exponential
      and the fluorescence lifetime of pyronin dyes in the concentrated PVA aqueous
      solution were also higher than those found in water.

PMID- 23123238
TI  - FT-IR, FT-Raman and UV spectral investigation: computed frequency estimation
      analysis and electronic structure calculations on 1-bromo-2-methylnaphthalene.
AB  - In this work, the vibrational spectral analysis was carried out by using FT-Raman
      and FT-IR spectroscopy in the range 100-4000 cm(-1) and 400-4000 cm(-1)
      respectively, for 1-bromo-2-methylnaphthalene (C11H9Br) molecule. The molecular
      structure, fundamental vibrational frequencies and intensity of the vibrational
      bands are interpreted with the aid of structure optimizations and normal
      coordinate force field calculations based density functional theory (DFT) and ab
      initio HF methods with different basis sets combinations. The complete
      vibrational assignments of wavenumbers were made on the basis of potential energy
      distribution (PED). The results of the calculations were applied to simulated
      vibrational spectra of the title compound, which show excellent agreement with
      observed spectra. The scaled B3LYP/6-311++G(d,p) results show the best agreement
      with the experimental values over the other methods. The energy and oscillator
      strength calculated by Time-Dependent Density Functional Theory (TD-DFT)
      complements with the experimental findings. In addition, molecular electrostatic
      potential and nonlinear optical and thermodynamic properties of the title
      compound were performed. Mulliken charges and NBOs of the title molecule were
      also calculated and interpreted.

PMID- 23123239
TI  - Fluorescent substituted amidines of benzanthrone: synthesis, spectroscopy and
      quantum chemical calculations.
AB  - Several new substituted amidine derivatives of benzanthrone were synthesized by a
      condensation reaction from 3-aminobenzo[de]anthracen-7-one and appropriate
      aromatic and aliphatic amides. The obtained derivatives have a bright yellow or
      orange fluorescence in organic solvents and in solid state. The novel
      benzanthrone derivatives were characterized by TLC analysis, (1)H NMR, IR, MS,
      UV/vis, and fluorescence spectroscopy. The solvent effect on photophysical
      behaviors of these dyes was investigated, and the results showed that the Stoke's
      shift increased, whereas quantum yield decreased with the growth of the solvent
      polarity. The structure of some dyes was confirmed by the X-ray single crystal
      structure analysis. AM1, ZINDO/S and ab initio calculations using Gaussian
      software were carried out to estimate the electron system of structures. The
      calculations show planar configurations for the aromatic core of these compounds
      and two possible orientations of amidine substituents. The calculation results
      correlate well with red-shifted absorption and emission spectra of compounds.

PMID- 23123240
TI  - Structural, electronic, thermodynamical and charge transfer properties of
      Chloramphenicol Palmitate using vibrational spectroscopy and DFT calculations.
AB  - The global problem of advancing bacterial resistance to newer drugs has led to
      renewed interest in the use of Chloramphenicol Palmitate (C27H42Cl2N2O6)
      [Palmitic acid alpha ester with D-threo-(-),2-dichloro-N-(beta-hydroxy-alpha
      (hydroxymethyl)-p-nitrophenethyl)acetamide also known as Detereopal]. The
      characterization of the three polymorphic forms of Chloramphenicol Palmitate
      (CPP) was done spectroscopically by employing FT-IR and FT-Raman techniques. The
      equilibrium geometry, various bonding features, and harmonic wavenumbers have
      been investigated for most stable form A with the help of DFT calculations and a
      good correlation was found between experimental data and theoretical values.
      Electronic properties have been analyzed employing TD-DFT for both gaseous and
      solvent phase. The theoretical calculation of thermodynamical properties along
      with NBO analysis has also been performed to have a deep insight into the
      molecule for further applications.

PMID- 23123241
TI  - Rapid photogeneration of silver nanoparticles in ethanolic solution: a kinetic
      study.
AB  - Ag nanoparticles have been synthesized via UV irradiation of ethanolic solution
      of AgNO3 in presence of pluronic F127 surfactant. This study is aimed at
      developing a rapid, simple and green method to prepare Ag nanoparticles and
      understanding its generation kinetics. The formation dependency of silver
      nanoparticles on the concentration of reactants, UV exposure time and temperature
      has been investigated by using UV-vis spectroscopy. The 2D map technique has been
      used for the first time to estimate the switching time between the nucleation and
      growth of Ag nanoparticles. Appropriate kinetic models were used for modelling of
      both stages.

PMID- 23123242
TI  - Sucrose as chiral selector for determining enantiomeric composition of metalaxyl
      by UV-vis spectroscopy and PLS regression.
AB  - This study revealed that it was possible to determine the enantiomeric
      composition of with multivariate regression models of spectral data obtained by
      ordinary UV-vis spectrophotometry of enantiomeric guest-host complexes. The total
      60samples involving three concentration levels of metalaxyl as low, medium and
      high were prepared for spectral collecting. Four methods of modeling were
      subsequently proposed and compared including two common ways and two compensating
      ways for variations in total analyte concentration. Firstly, without
      normalization robust modeling was failed to achieve while employing the medium
      concentration levels as calibration and the other two levels as a validation. The
      same case occurred when full-cross validation was conducted. Besides, two
      enhanced methods were developed to account for the systematic variation. One of
      which normalized the spectra with respect to the total concentration of
      enantiomeric, along with spectral data, as a variable in the statistical
      analysis. The other one ignored variations in total concentration, relying on the
      specific band normalization to sort out any variations due to total concentration
      differences. The results clearly demonstrated that the spectra according to
      concentration provided the acceptable predictive ability in determining
      enantiomeric composition.

PMID- 23123243
TI  - Vibrational spectral analysis, computation of thermodynamic functions for various
      temperatures and NBO analysis of 2,3,4,5-tetrachlorophenol using ab initio HF and
      DFT calculations.
AB  - FT-IR and FT-Raman spectra of 2,3,4,5-tetrachlorophenol (TCP) have been recorded
      in the regions 4000-400 cm(-1) and 3500-100 cm(-1) respectively. The total energy
      calculations of TCP were tried for the possible conformers. The molecular
      structure, geometry optimization, vibrational frequencies were obtained by the ab
      initio and DFT levels of theory (B3LYP and B3PW91) with the standard basis sets,
      6-311++G(d, p) and 6-311+G(d, p) for C1 and C2 conformers. The harmonic
      frequencies were calculated and the scaled values were compared with experimental
      FT-IR and FT-Raman spectra. The observed and the calculated frequencies are found
      to be in good agreement. Stability of the molecule arising from hyper conjugative
      interactions, charge delocalization has been analyzed using natural bond orbital
      (NBO) analysis. The thermodynamic functions (heat capacity, entropy, vibrational
      partition function and Gibbs energy) from spectroscopic data by statistical
      methods were obtained for the range of temperature 100-1000 K. The
      polarizability, first hyperpolarizability, anisotropy polarizability invariant
      has been computed using quantum chemical calculations. The chemical parameters
      were calculated from the HOMO and LUMO values.

PMID- 23123245
TI  - Structural characterization of rondorfite, calcium silica chlorine mineral
      containing magnesium in tetrahedral position [MgO4]6-, with the aid of the
      vibrational spectroscopies and fluorescence.
AB  - Raman and infrared spectra of rondorfite Ca8Mg(SiO4)4Cl2, a calcium chlorosilica
      mineral containing magnesium in tetrahedral position, has been studied in terms
      of spectra-structure relations. Raman spectra have been measured at different
      excited laser lines: 780 nm, 532 nm, 488 nm and 457 nm. This mineral is
      characterized by a single sharp intense Raman band at 863 cm(-1) assigned to the
      nu1 [SiO4]4- (Ag) symmetric stretching mode in the magnesiosilicate pentamer. Due
      to symmetry restriction the other Raman bands have a small intensity. Two Raman
      bands observed at 564 cm(-1) and 526 cm(-1) are associated simultaneously with
      nu4 [MgO4]6- and nu4 [SiO4]4- symmetric and antisymmetric modes where magnesium
      occurs in the tetrahedral configuration. The weak bands at 422 cm(-1) and 386 cm(
      1) are associated with the nu2 bending mode of CaO6 in octahedral configuration,
      respectively. Moreover the infrared spectrum shows very weak bands associated
      with the hydroxyl group and/or water molecule. Additionally, the strong
      fluorescence phenomenon was observed and related to the presence of chlorine
      atoms, magnesium Mg2+ ions in atypical configuration or point defects.

PMID- 23123244
TI  - Molecular structure, Normal Coordinate Analysis, harmonic vibrational
      frequencies, Natural Bond Orbital, TD-DFT calculations and biological activity
      analysis of antioxidant drug 7-hydroxycoumarin.
AB  - In this work, we report harmonic vibrational frequencies, molecular structure,
      NBO and HOMO, LUMO analysis of Umbelliferone also known as 7-hydroxycoumarin
      (7HC). The optimized geometric bond lengths and bond angles obtained by
      computation (monomer and dimmer) shows good agreement with experimental XRD data.
      Harmonic frequencies of 7HC were determined and analyzed by DFT utilizing 6
      311+G(d,p) as basis set. 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 Methodology (SQMFF). The change in electron
      density (ED) in the sigma* and pi* antibonding orbitals and stabilization
      energies E(2) have been calculated by Natural Bond Orbital (NBO) analysis to give
      clear evidence of stabilization originating in the hyperconjugation of hydrogen
      bonded interaction. The energy and oscillator strength calculated by Time
      Dependent Density Functional Theory (TD-DFT) complements with the experimental
      findings. The simulated spectra satisfactorily coincides with the experimental
      spectra. Microbial activity of studied compounds was tested against
      Staphylococcus aureus, Streptococcus pyogenes, Bacillus subtilis, Escherichia
      coli, Psuedomonas aeruginosa, Klebsiella pneumoniae, Proteus mirabilis, Shigella
      flexneri, Salmonella typhi and Enterococcus faecalis.

PMID- 23123246
TI  - Theoretical calculations and surface morphology studies of L-threonine formate.
AB  - In order to investigate microscopic second order nonlinear optical properties of
      L-threonine formate (abbreviated as LTF) crystals, the molecular dipole moment
      (MU), polarizability (alpha), and first hyperpolarizability (beta) were computed
      using a series of basis sets including polarized and diffuse functions at the
      framework of Hartree-Fock and density functional theory methods. In addition, the
      grown crystal surface has been analyzed by atomic force microscopy (AFM). The
      formation mechanisms of the hollow cavity defect on growth surface have been
      analyzed.

PMID- 23123247
TI  - Functionalized cyclodextrins bearing an alpha nucleophile--a promising way to
      degrade nerve agents.
AB  - Organophosphorus nerve agents are irreversible inhibitors of
      acetylcholinesterase. Current treatment of nerve agent poisoning has limited
      efficacy and more efficient medical countermeasures need to be developed. A
      promising approach is to design chemical scavengers more stable during storage
      and less immunogenic than bioscavengers. Furthermore, they could be produced at
      lowest production costs. Cyclodextrins are attractive cyclic oligosaccharides
      that can be used to develop chemical scavengers of organophosphorus nerve agents.
      Their abilities to form inclusion and non-inclusion complexes with organic
      substrates are useful to trap chemical warfare agents. Selective introduction of
      an alpha-nucleophile residue on the secondary face of beta-cyclodextrin allowed
      to obtain supramolecular derivatives active against organophosphorus compounds.
      The degradation activity of these monosubstituted cyclodextrins was determined
      against paraoxon and chemical warfare agents. These tests showed that the
      structure of the scavengers mainly influences the interaction between the
      organophosphorus substrate, or its reaction products, and the cyclodextrin
      moiety. All the tested G-type agents were efficiently degraded. According to the
      binding modes of cyclosarin, some oligosaccharidic scavengers led to an
      enantioselective degradation of this nerve agent. These promising derivatives
      open the way to further investigations of new structural modifications to reach
      more sophisticated and efficient scavengers for prophylactic and curative medical
      applications.

PMID- 23123248
TI  - Inhibition of human carboxylesterases hCE1 and hiCE by cholinesterase inhibitors.
AB  - Carboxylesterases (CEs) are ubiquitously expressed proteins that are responsible
      for the detoxification of xenobiotics. They tend to be expressed in tissues
      likely to be exposed to such agents (e.g., lung and gut epithelia, liver) and can
      hydrolyze numerous agents, including many clinically used drugs. Due to the
      considerable structural similarity between cholinesterases (ChE) and CEs, we have
      assessed the ability of a series of ChE inhibitors to modulate the activity of
      the human liver (hCE1) and the human intestinal CE (hiCE) isoforms. We observed
      inhibition of hCE1 and hiCE by carbamate-containing small molecules, including
      those used for the treatment of Alzheimer's disease. For example, rivastigmine
      resulted in greater than 95% inhibition of hiCE that was irreversible under the
      conditions used. Hence, the administration of esterified drugs, in combination
      with these carbamates, may inadvertently result in decreased hydrolysis of the
      former, thereby limiting their efficacy. Therefore drug:drug interactions should
      be carefully evaluated in individuals receiving ChE inhibitors.

PMID- 23123249
TI  - Testing of novel brain-penetrating oxime reactivators of acetylcholinesterase
      inhibited by nerve agent surrogates.
AB  - A critical need for combating the effects of organophosphate (OP)
      anticholinesterases, such as nerve agents, is the current lack of an effective
      oxime reactivator which can penetrate the blood-brain barrier (BBB), and
      therefore reactivate inhibited acetylcholinesterase (AChE) in the brain. Our
      laboratories have synthesized and have initiated testing of novel phenoxyalkyl
      pyridinium oximes (patent pending) that are more lipophilic than currently
      approved oximes. This is a preliminary report on these novel oximes which have
      been tested in vitro in rat brain homogenates with highly relevant surrogates for
      sarin (phthalimidyl isopropyl methylphosphonate; PIMP) and VX (nitrophenyl ethyl
      methylphosphonate; NEMP). The oximes demonstrated a range of 14-76% reactivation
      of rat brain AChE in vitro. An in vivo testing paradigm was developed in which
      the novel oxime was administered at the time of maximal brain AChE inhibition
      (about 80%) (1h) elicited by nitrophenyl isopropyl methylphosphonate (NIMP; sarin
      surrogate). This paradigm, with delayed administration of oxime to a time when
      brain AChE was starting to recover, was designed to minimize
      reactivation/reinhibition of peripheral AChE during the reactivation period which
      would decrease the availability of the surrogate for entry into the brain; this
      paradigm will allow proof of concept of BBB penetrability. The initial studies of
      these oximes in vivo with the sarin surrogate NIMP have indicated reactivation of
      up to about 25% at 30 min after oxime administration and substantial attenuation
      of seizure behavior from some of the oximes. Therefore these novel oximes have
      considerable potential as brain-protecting therapeutics for anticholinesterases.

PMID- 23123250
TI  - A combination of [+] and [-]-Huperzine A improves protection against soman
      toxicity compared to [+]-Huperzine A in guinea pigs.
AB  - The neuropathologic mechanisms after exposure to lethal doses of nerve agent are
      complex and involve multiple biochemical pathways. Effective treatment requires
      drugs that can simultaneously protect by reversible binding to the
      acetylcholinesterase (AChE) and blocking cascades of seizure related brain
      damage, inflammation, neuronal degeneration as well as promoting induction of
      neuroregeneration. [-]-Huperzine A ([-]-Hup A), is a naturally occurring potent
      reversible AChE inhibitor that penetrates the blood-brain barrier. It also has
      several neuroprotective effects including modification of beta-amyloid peptide,
      reduction of oxidative stress, anti-inflammatory, anti-apoptotic and induction
      and regulation of nerve growth factor. Toxicities at higher doses restrict the
      neuroporotective ability of [-]-Hup A for treatment. The synthetic stereoisomer,
      [+]-Hup A, is less toxic due to poor AChE inhibition and is suitable for both pre
      /post-exposure treatments of nerve agent toxicity. [+]-Hup A block the N-methyl-D
      aspartate (NMDA)-induced seizure in rats, reduce excitatory amino acid induced
      neurotoxicity and also prevent soman induced toxicity with minimum performance
      decrement. Unique combinations of two stereo-isomers of Hup A may provide an
      excellent pre/post-treatment drug for the nerve agent induced seizure/status
      epilepticus. We investigated a combination of [+]-Hup A with a small dose of [-]
      Hup A ([+] and [-]-Hup A) against soman toxicity. Our data showed that
      pretreatment with a combination [+] and [-]-Hup A significantly increased the
      survival rate and reduced behavioral abnormalities after exposure to 1.2 * LD(50)
      soman compared to [+]-Hup A in guinea pigs. In addition, [+] and [-]-Hup A
      pretreatment inhibited the development of high power of EEG better than [+]-Hup A
      pretreatment alone. These data suggest that a combination of [+] and [-]-Hup A
      offers better protection than [+]-Hup A and serves as a potent medical
      countermeasure against lethal dose nerve agent toxicity in guinea pigs.

PMID- 23123251
TI  - Organophosphorus compound esterase profiles as predictors of therapeutic and
      toxic effects.
AB  - Certain organophosphorus compounds (OPCs) inhibit various serine esterases (EOHs)
      via phosphorylation of their active site serines. We focused on 4 EOHs of
      particular toxicological interest: acetylcholinesterase (AChE: acute
      neurotoxicity; cognition enhancement), butyrylcholinesterase (BChE: inhibition of
      drug metabolism and/or stoichiometric scavenging of EOH inhibitors; cognition
      enhancement), carboxylesterase (CaE: inhibition of drug metabolism and/or
      stoichiometric scavenging of EOH inhibitors), and neuropathy target esterase
      (NTE: delayed neurotoxicity, OPIDN). The relative degree of inhibition of these
      EOHs constitutes the "esterase profile" of an OPC and serves as a major
      determinant of its net physiological effects. Thus, understanding and controlling
      the esterase profile of OPC activity and selectivity toward these 4 target
      enzymes is a significant undertaking. In the present study, we analyzed the
      inhibitor properties of 52 OPCs against the 4 EOHs, along with pairwise and
      multitarget selectivities between them, using 2 QSAR approaches: Hansch modeling
      and Molecular Field Topology Analysis (MFTA). The general formula of the OPCs was
      (RO)(2)P(O)X, where R = alkyl, X = - SCH(Hal)COOEt (Hal = Cl, Br), -SCHCl(2), 
      SCH(2)Br, -OCH(CF(3))R(1) (R(1) = C(6)H(5), CF(3), COOEt, COOMe). The Hansch
      model showed that increasing neuropathic potential correlated with rising R
      hydrophobicity; moreover, OPC binding to scavenger EOHs (BChE and CaE) had
      different effects on potential acute and delayed neurotoxicity. Predicted
      protective roles of BChE and CaE against acute toxicity were enhanced with
      increasing hydrophobicity, but projected protection against OPIDN was decreased.
      Next, Molecular Field Topology Analysis (MFTA) models were built, considering
      atomic descriptors, e.g., effective charge, van der Waals radius of environment,
      and group lipophilicity. Activity/selectivity maps confirmed predictions from
      Hansch models and revealed other structural factors affecting activity and
      selectivity. Virtual screening based on multitarget selectivity MFTA models was
      used to design libraries of OPCs with favorable esterase profiles for potential
      application as selective inhibitors of CaE without untoward side effects.

PMID- 23123253
TI  - New tools in diagnosis and biomonitoring of intoxications with
      organophosphorothioates: case studies with chlorpyrifos and diazinon.
AB  - Organophosphate (OP) pesticides are neurotoxic compounds that are widely used in
      agriculture. Classical methods for monitoring OP exposure comprise the
      measurement of intact OP, its metabolites or cholinesterase activity. Newly
      developed methods focus on the analysis of the OP adduct bound to proteins such
      as butyrylcholinesterase (BuChE) and albumin. These adducts can be analyzed by
      means of fluoride reactivation or by analysis with LC-MS/MS of the pepsin or
      pronase digest of butyrylcholinesterase and albumin, respectively. The utility of
      these methods is illustrated through the analysis of plasma samples obtained from
      patients taken 1-49 days after ingestion of the organophosphate pesticides
      chlorpyrifos and/or diazinon. Thus, in this particular case several independent
      methodologies were applied to the biomedical samples, all pointing to the same
      exposure.

PMID- 23123252
TI  - Proteomic analysis of adducted butyrylcholinesterase for biomonitoring
      organophosphorus exposures.
AB  - Organophosphorus (OP) compounds include a broad group of toxic chemicals such as
      insecticides, chemical warfare agents and antiwear agents. The liver cytochromes
      P450 bioactivate many OPs to potent inhibitors of serine hydrolases.
      Cholinesterases were the first OP targets discovered and are the most studied.
      They are used to monitor human exposures to OP compounds. However, the assay that
      is currently used has limitations. The mechanism of action of OP compounds is the
      inhibition of serine hydrolases by covalently modifying their active-site serine.
      After structural rearrangement, the complex OP inhibitor-enzyme is irreversible
      and will remain in circulation until the modified enzyme is degraded. Mass
      spectrometry is a sensitive technology for analyzing protein modifications, such
      as OP-adducted enzymes. These analyses also provide some information about the
      nature of the OP adduct. Our aim is to develop high-throughput protocols for
      monitoring OP exposures using mass spectrometry.

PMID- 23123254
TI  - Assessing protection against OP pesticides and nerve agents provided by wild-type
      HuPON1 purified from Trichoplusia ni larvae or induced via adenoviral infection.
AB  - Human paraoxonase-1 (HuPON1) has been proposed as a catalytic bioscavenger of
      organophosphorus (OP) pesticides and nerve agents. We assessed the potential of
      this enzyme to protect against OP poisoning using two different paradigms. First,
      recombinant HuPON1 purified from cabbage loopers (iPON1; Trichoplusia ni) was
      administered to guinea pigs, followed by exposure to at least 2 times the median
      lethal dose (LD(50)) of the OP nerve agents tabun (GA), sarin (GB), soman (GD),
      and cyclosarin (GF), or chlorpyrifos oxon, the toxic metabolite of the OP
      pesticide chlorpyrifos. In the second model, mice were infected with an
      adenovirus that induced expression of HuPON1 and then exposed to sequential doses
      of GD, VX, or (as reported previously) diazoxon, the toxic metabolite of the OP
      pesticide diazinon. In both animal models, the exogenously added HuPON1 protected
      animals against otherwise lethal doses of the OP pesticides but not against the
      nerve agents. Together, the results support prior modeling and in vitro activity
      data which suggest that wild-type HuPON1 does not have sufficient catalytic
      activity to provide in vivo protection against nerve agents.

PMID- 23123255
TI  - Strategies for the selection of catalytic antibodies against organophosphorus
      nerve agents.
AB  - Among the strategies aimed at biocompatible means for organophosphorus nerve
      agents neutralization, immunoglobulins have attracted attention in the 1990's and
      2000's both for their ability to immobilize the toxicants, but also for their
      ability to be turned into enzymatically active antibodies known as catalytic
      antibodies or abzymes (antibodies--enzymes). We will present here a critical
      review of the successive strategies used for the selection of these nerve agent
      hydrolyzing abzymes, based on hapten design, namely antibodies raised against a
      wide variety of transition state analogs, and eventually the strategies based on
      anti-idiotypic antibodies and reactibodies.

PMID- 23123256
TI  - Minor neurological dysfunction and cognition in 9-year-olds born at term.
AB  - BACKGROUND: In children with developmental disorders, motor problems often co
      occur with cognitive difficulties. Associations between specific cognitive
      deficits underlying learning problems and minor neurological dysfunction (MND)
      are still unknown. AIMS: To assess associations between specific types of MND as
      clinical markers of non-optimal brain function and performance in specific
      cognitive domains. STUDY DESIGN: Part of a randomized controlled trial. SUBJECTS:
      Three hundred and forty one 9-year-old children born at term (177 boys, 164
      girls). OUTCOME MEASURES: Children were neurologically assessed to detect eight
      types of MND: mild dysfunction in posture and muscle tone, reflexes,
      coordination, fine manipulative ability, sensory function, cranial nerve
      function, choreiform dyskinesia and excessive associated movements. Cognitive
      function in the domains of attention, memory and language was evaluated using the
      Test of Everyday Attention for Children (TEA-Ch), a developmental
      neuropsychological assessment (NEPSY) and the Children's Memory Scale. RESULTS:
      Fine manipulative disability and coordination problems were associated with lower
      scores on attention, memory and learning and language, other types of MND were
      not. Girls with coordination problems performed significantly worse on
      attention/executive function than those without this dysfunction; however, in
      boys, such association was absent. CONCLUSION: Particularly, fine manipulative
      disability and coordination problems were associated with worse cognitive
      function in the domains of attention, learning and memory and language. Previous
      and present data suggest a minor sex difference in neurocognitive associations:
      in girls dysfunction of the cerebello-thalamo-cortical pathways may be associated
      with cognitive deficits, while in boys cognitive impairment may be associated
      with dysfunction of cortico-striato-thalamo-cortical pathways.

PMID- 23123257
TI  - Reduced in vitro and in vivo toxicity of siRNA-lipoplexes with addition of
      polyglutamate.
AB  - We previously designed a new siRNA vector that efficiently silences genes in
      vitro and in vivo. The vector originality is based on the fact that, in addition
      to the siRNA molecule, it contains two components: 1) a cationic liposome that
      auto-associates with the siRNA to form particles called "lipoplexes" and, 2) an
      anionic polymer which enhances the lipoplex's efficiency. This anionic polymer
      can be a nucleic acid, a polypeptide or a polysaccharide. We show here how the
      nature of the added anionic polymer into our siRNA delivery system impacts the
      toxic effects induced by siRNA lipoplexes. We first observed that: (i) siRNA
      lipoplexes-induced toxicity was cell line dependent, tumoral cell lines being the
      more sensitive; and (ii) plasmid DNA-containing siRNA lipoplexes were more toxic
      than polyglutamate-containing ones or cationic liposomes. We next determined that
      the toxicity induced by plasmid-containing lipoplexes is a long-lasting effect
      that decreased cell survival capacity for several generations. We also found that
      treated cells underwent death following apoptosis pathway. Systemic injection to
      mice of siRNA lipoplexes, rather than of cationic liposome, triggered a
      production of several cytokines in mice and replacement of plasmid by
      polyglutamate reduced the elevation of all assayed cytokines. In order to enhance
      siRNA lipoplexes efficiency, the addition of polyglutamate as anionic polymer
      should be preferred to plasmid DNA as far as in vitro as well as in vivo toxicity
      is concerned.

PMID- 23123258
TI  - Behavioral phase shift in nymphs of the desert locust, Schistocerca gregaria:
      special attention to attraction/avoidance behaviors and the role of serotonin.
AB  - Schistocerca gregaria exhibits a phase-specific behavior in response to crowding.
      Nymphs occurring at low population densities (solitarious phase) tend to avoid
      one another, whereas those occurring at high population densities (gregarious
      phase) are attracted to one another. This study examined how this
      attraction/avoidance behavior changed after isolation or crowding. The behavior
      of the test nymphs was assessed by determining their positioning with respect to
      a stimulus cup, which contained 12 gregarious nymphs, placed at one end of an
      elliptical arena and an empty cup placed at the opposite end. Gregarious (crowd
      reared) nymphs were most frequently observed close to the stimulus cup, whereas
      solitarious (isolated-reared) nymphs tended to avoid it. This tendency was easily
      changed by exposing the nymphs to isolation or crowding. However, contrary to a
      previously reported conclusion that behavioral gregarization occurs in 4-8 h of
      crowding, the nymphs required at least 3 days to achieve a significant change in
      the attraction/avoidance behavior in either direction, from solitarious to
      gregarious or the converse. The discrepancies between the present study and
      previous studies appear to result from the different behaviors observed. The
      present study focused on the attraction/avoidance behavior that is most likely
      the most important element in the gregarization and solitarization processes,
      whereas other studies used a mixture of various activity-related behaviors. No
      evidence was obtained for a trans-generational accumulation in the
      attraction/avoidance behaviors. Serotonin, a biogenic amine that is suggested by
      others to be involved in behavioral phase changes in S. gregaria, had no
      influence on this behavior or body color when injected into the solitarious
      nymphs.

PMID- 23123259
TI  - Metabolic fingerprinting of the responses to salinity in the invasive ground
      beetle Merizodus soledadinus at the Kerguelen Islands.
AB  - Salinity is an abiotic factor that may impact survival and fitness of terrestrial
      insects in coastal environments. Meanwhile, some terrestrial arthropods can
      survive in hypersaline environments, and counterbalance osmotic stress by intra-
      and extracellular buildups of organic osmolytes. The ground beetle Merizodus
      soledadinus originates from South America and it is distributed in forests and
      riparian zones, where salinity levels are considerably low. This species has been
      introduced at the Kerguelen Islands a century ago, where it colonized coastal
      areas (tide drift lines), and must thus withstand salinity variations due to
      tide, spray, and organic matter deposited therein. In the present study, we
      addressed the physiological plasticity of M. soledadinus to saline conditions, by
      monitoring body water content and survival in adults experimentally subjected to
      different salinities. We also investigated possible metabolic adjustments
      involved at three contrasted salinity levels (00/00, 350/00, 700/00) at 4 and 8
      degrees C. We hypothesized that this invasive ground beetle can withstand a broad
      range of salinity conditions thanks to the plastic accumulation of compatible
      solutes. The study revealed a progressive drop in body water content in
      individuals exposed to 350/00 and 700/00, as opposed to the controls. Metabolic
      fingerprints showed compatible solute (erythritol, alanine, glycine and proline)
      accumulation at medium and high salinity conditions (350/00 and 700/00). We
      concluded that the osmo-induced accumulation of amino acids and polyols was
      likely to modulate the ground beetles' body water balance on medium saline
      substrates, thus enhancing their survival ability.

PMID- 23123260
TI  - Cellulase production by Penicillium funiculosum and its application in the
      hydrolysis of sugar cane bagasse for second generation ethanol production by fed
      batch operation.
AB  - This study aimed to produce a cellulase blend and to evaluate its application in
      a simultaneous saccharification and fermentation (SSF) process for second
      generation ethanol production from sugar cane bagasse. The sugar cane bagasse was
      subjected to pretreatments (diluted acid and alkaline), as for disorganizing the
      ligocellulosic complex, and making the cellulose component more amenable to
      enzymatic hydrolysis. The residual solid fraction was named sugar cane bagasse
      partially delignified cellulignin (PDC), and was used for enzyme production and
      ethanol fermentation. The enzyme production was performed in a bioreactor with
      two inoculum concentrations (5 and 10% v/v). The fermentation inoculated with
      higher inoculum size reduced the time for maximum enzyme production (from 72 to
      48). The enzyme extract was concentrated using tangential ultrafiltration in
      hollow fiber membranes, and the produced cellulase blend was evaluated for its
      stability at 37  degrees C, operation temperature of the simultaneous SSF
      process, and at 50  degrees C, optimum temperature of cellulase blend activity.
      The cellulolytic preparation was stable for at least 300 h at both 37  degrees C
      and 50  degrees C. The ethanol production was carried out by PDC fed-batch SSF
      process, using the onsite cellulase blend. The feeding strategy circumvented the
      classic problems of diffusion limitations by diminishing the presence of a high
      solid:liquid ratio at any time, resulting in high ethanol concentration at the
      end of the process (100 g/L), which corresponded to a fermentation efficiency of
      78% of the maximum obtainable theoretically. The experimental results led to the
      ratio of 380 L of ethanol per ton of sugar cane bagasse PDC.

PMID- 23123261
TI  - A 26-week repeated dose toxicity study of Xian-ling-gu-bao in Sprague-Dawley
      rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Xian-ling-gu-bao (XLGB) is a traditional Chinese
      prescription commonly used to treat osteoporosis, osteoarthritis, aseptic bone
      necrosis, climacteric syndrome, and bone fracture. However, there is limited
      toxicological information available on XLGB in preclinical animal model studies.
      It has also been recently reported that XLGB may be related to liver injury in
      humans. AIM OF STUDY: This study was designed to determine the potential toxic
      effects of XLGB, particularly hepatotoxicity, in Sprague-Dawley rats following
      oral administration for up to 26 weeks. MATERIALS AND METHODS: Male and female
      rats were administered XLGB by oral gavage at doses of 0, 100, 300, and 1000
      mg/kg for 26 weeks followed by a recovery period of 4 weeks. Clinical signs, body
      weight, food consumption, ophthalmology, hematology, coagulation, serum
      chemistry, urinalysis, bone mineral density, hormone concentration, organ weights
      and histopathology were examined at the end of 13- and 26-week dosing period as
      well as after the recovery period. RESULTS: Neither hepatotoxicity nor any other
      toxic effects were observed in the XLGB treated rats at doses up to 1000 mg/kg
      for 26 weeks except for a slight increase in the organ weight of the uterus in
      female rats at doses higher than 300 mg/kg on week 26. CONCLUSIONS: In this
      study, we found the no-observed-adverse-effect level (NOAEL) for XLGB in Sprague
      Dawley rats was 1000 mg/kg, a dose that was equivalent to 3.3 times human dose
      based on body surface area.

PMID- 23123262
TI  - Neuroprotective effect of calycosin on cerebral ischemia and reperfusion injury
      in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Radix Astragali has been commonly used as
      traditional herbal medicine in China for reinforcing vital energy, strengthening
      superficial resistance and promoting the discharge of pus and the growth of new
      tissue. AIM OF THE STUDY: The present study was to investigate the
      neuroprotective effect of calycosin isolated from the roots of Radix Astragali on
      cerebral ischemic/reperfusion injury. MATERIALS AND METHODS: After 24h of
      reperfusion following ischemia for 2h induced by middle cerebral artery occlusion
      (MCAO), Sprague-Dawley rats were intragastrically administered different doses of
      calycosin (7.5, 15, 30 mg/kg, respectively). Neurological deficit, infarct
      volume, histopathology changes and some oxidative stress markers were evaluated
      after 24h of reperfusion. RESULTS: Treatment with calycosin significantly
      ameliorated neurologic deficit and infarct volume after cerebral ischemia
      reperfusion. Calycosin also reduced the content of malondialdehyde (MDA), protein
      carbonyl and reactive oxygen species (ROS), and up-regulated the activities of
      superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-Px) in a
      dose-dependent manner. Moreover, calycosin can also inhibit the expression of 4
      Hydroxy-2-nonenal (4-HNE). CONCLUSION: These results suggest that calycosin has a
      neuroprotective effect against cerebral ischemia/reperfusion injury. The
      mechanism might be attributed to its antioxidant effects.

PMID- 23123263
TI  - Substantiation of the ethnopharmacological use of Conyza sumatrensis (Retz.)
      E.H.Walker in the treatment of malaria through in-vivo evaluation in Plasmodium
      berghei infected mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Scientific validation of ethnopharmacologically
      used plants and their utilization for therapeutic interventions can be a source
      of affordable treatment especially for neglected diseases in endemic areas.
      Conyza sumatrensis is a plant which finds its use in treating malaria like fevers
      but lacks proper scientific validation. Our study has tried to address this gap
      by authenticating its traditional use for the treatment of malaria. AIM OF THE
      STUDY: Evaluate the antimalarial activity of extracts derived from Conyza
      sumatrensis for its ethnopharmacological validation. MATERIALS AND METHODS: Shade
      dried leaves were extracted with varying concentrations of ethanol and
      concentrated for bio-evaluation. Swiss albino mice infected with 1 * 10(6)
      parasitized red blood cells, were orally administered with test extracts for 7
      days in two sets of experiments. The first set was used to evaluate alcoholic,
      hydroalcoholic and aqueous extracts while the second set was used to evaluate the
      dose response of alcoholic extract ranging from 500-1600 mg/kg. Mean survival
      time, parasitaemia and haemoglobin levels were considered to interpret the
      antimalarial potential. Phytochemical analysis for the presence of flavonoids,
      alkaloids tannins, total phenolics, riboflavin and thiamine was also carried out.
      RESULTS: Among the three extracts administered at 1000 mg/kg, chemo suppression
      was significantly (p<0.001) observed in the alcoholic extract (62.59 +/- 12.52%)
      followed by hydroalcoholic (41.81 +/- 19.04%, p<0.01) and aqueous (32.04 +/-
      19.04%, P<0.05) indicating that the active constituents leach out in ethanol. The
      dose response study involving the ethanol extract concluded the optimum dose to
      be 1000 mg/kg, as also evidenced by the haemoglobin levels. CONCLUSION: The plant
      exhibits moderate antimalarial activity which can be further prospected for
      active fractions or pure molecules for adjunctive therapy.

PMID- 23123264
TI  - Antinociceptive, anti-inflammatory and antioxidant activities of aqueous extract
      from Remirea maritima (Cyperaceae).
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Remirea maritima Aubl., popularly known as "capim
      da-praia", is popularly employed in the treatment of diarrhea, kidney disease,
      fever, and for analgesic and anti-inflammatory purposes through the preparation
      of teas. Few studies have focused on the chemical composition and its biological
      properties. AIM OF THE STUDY: This work evaluated the antinocipetive, anti
      inflammatory and antioxidant activities of the aqueous extract from Remirea
      maritima Aubl. as well as the isolation and identification of the chemical
      compounds. MATERIALS AND METHODS: Compounds were isolated from aqueous extract of
      Remirea maritima through preparative HPLC and the structures were identified by
      means of NMR and MS analysis. The tests for antinociceptive, anti-inflammatory,
      and antioxidant activities, along with motor coordination test (Rota rod), were
      performed over the aqueous extract. RESULTS: The phytochemical investigation of
      aqueous extract of Remirea maritima resulted in the isolation of three flavone
      glycosides. The structures of these compounds were determined by means of MS and
      1D and 2D NMR data as vitexin-2"-O-beta-D-glucopyranoside, isovitexin-2"-O-beta-D
      glucopyranoside, and luteolin-7-O-glucuronide. Acute pretreatment with aqueous
      extract (100, 200 or 400mg/kg, i.p.) caused a significant decrease (p<0.001) in
      the number of abdominal writhes. In the formalin test, higher doses significantly
      inhibited the late (inflammatory pain) phase of formalin-induced licking (p<0.05
      or 0.001). In the hot plate test, there was no significant difference in
      nociceptive behavior, discarding the possible central effect of the aqueous
      extract. In the rota rod test, it was verified that the aqueous extract in all
      concentration evaluated does not alter the motor coordination of mice, such
      antinociceptive results were unlikely to be caused by motor abnormality. In the
      peritonitis test, induced by carrageenan, the treatment with aqueous extract
      produced a significant reduction in leukocyte migration in all concentration
      evaluated. Additionally, a significant reduction of lipoperoxidation (TBARS test)
      and in nitric oxide formation (.NO Scavenging assay) was observed in antioxidant
      activity assay. CONCLUSION: The biological and phytochemical investigations of
      the aqueous extract of Remirea maritima resulted in the identification of three
      flavone glycosides that have been described here for the first time in Remirea
      and effective analgesic activity in various pain models, probably mediated via
      the inhibition of peripheral mediators which could be related to its strong
      antioxidant effect observed in vitro.

PMID- 23123265
TI  - Subchronic oral toxicity studies of the traditional herbal formula
      Bangpungtongseong-san in Crl: CD (SD) rats.
AB  - AIM OF THE STUDY: The clinical usefulness of medications generally depends on
      their efficacy and safety. Bangpungtongsung-san (BPTS), a traditional herbal
      medicine, is widely used to treat patients in Korea, Japan (Bofu-tsusho-san), and
      China (Fang feng tong sheng-san) as an antiobesity prescription. The objective of
      the present study was to evaluate the subchronic toxicity of a BPTS water extract
      in Crl:CD SD rats. MATERIALS AND METHODS: BPTS was administered to rats orally
      once daily at doses of 0, 500, 1000, and 2000 mg/kg/day for 13 weeks.
      Toxicological parameters included clinical signs, body weight, water and food
      consumption, ophthalmological signs, relative organ weight, hematological and
      serum biochemical parameters, and histopathological assessment. RESULTS: No
      treatment-related adverse effects were observed regarding the physiological
      parameters examined during the study or in the evaluation of blood, urea, and
      tissue samples taken from the animals at the end of the study. CONCLUSIONS: In
      conclusion, the no-observed-adverse-effect-level for BPTS was determined to be a
      dietary dose of over 2000 mg/kg for both sexes under the present experimental
      conditions.

PMID- 23123266
TI  - Croton lechleri sap and isolated alkaloid taspine exhibit inhibition against
      human melanoma SK23 and colon cancer HT29 cell lines.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Croton lechleri Mull. Arg. (Euphorbiaceae) is a
      traditional medicinal plant which produces a red sap, traditionally known as
      "Sangre de Drago"; it is used in folk medicine externally for wounds, fractures,
      and haemorrhoids, internally for intestinal and stomach ulcers and also for the
      empirical cure of cancers. MATERIALS AND METHODS: We investigated the effects of
      Croton lechleri sap and taspine in comparison with taxol and vinblastine on the
      growth of human cancer cell lines of SK23 (melanoma), LoVo and HT29 (colorectal
      cancer) using MTT and Trypan blue assays. Further, we studied cell cycle by flow
      cytometry and detected acetylated-alpha-tubulin by confocal microscope. RESULTS:
      Croton lechleri inhibited cell proliferation starting from 1 MUg/mL in SK23
      cells, whereas 10 times higher concentrations were required for growth inhibition
      of HT-29 and LoVo cell lines. Also taspine (0.1 MUg/mL) inhibited the SK23 and
      HT29 cell proliferation. Further, assay was assessed on SK23 and HT29 cell lines
      with 24-48 h treatment with sap and taspine. Both sap and taspine inhibited
      cancer cell proliferation; taspine showed higher activity on SK23 cells, which
      was significantly increased after 48 h of SK23 treatment. Using confocal
      microscopy we observed that Croton lechleri (1 MUg/mL) caused a loss of
      microtubule structure, whereas taspine (0.5 MUg/mL) caused an increase in
      acetylated alpha-tubulin and a modification of cellular morphology, mainly in
      SK23 cells. Croton lechleri sap 10 and 50 MUg/mL influence cell cycle; 50 MUg/mL
      sap caused a dramatic reduction of cells in G(1)/G(0) and S phases with a great
      increase of subG(0) cells. CONCLUSIONS: The data showed that Croton lechleri and
      taspine could inhibit cell proliferation with higher potency against melanoma
      SK23 cells, supporting the empirical use of the sap as anticancer in
      ethnomedicine and taspine as a possible anticancer agent.

PMID- 23123268
TI  - Plants as medicinal stressors, the case of depurative practices in Chazuta valley
      (Peruvian Amazonia).
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Depurative practices, based on taking emetic
      plants and the restriction of food intake, are very much used in the traditional
      medicine of Chazuta (Peruvian Amazon) not only to restore health but also to
      maintain it. AIM OF THE STUDY: To describe Chazuta's depurative practices, within
      a theoretical framework that involves the stress system and which defines the
      role played by the medicinal plants used as medicinal stressors. This biomedical
      model is more inclusive in relation to the variety of medicinal uses found for
      these practices. MATERIAL AND METHODS: The information was obtained in the valley
      of Chazuta from October 2004 to August 2005 through semi-structured interviews to
      the 6.3% of its rural adult population (i.e., 140 individuals, 75% belonging to
      the San Martin Quechua's ethnic group). Thereafter, results were analysed and
      confronted to the existing literature. RESULTS: Overall, 191 depurative practices
      were reported in Chazuta where 114 different plant species were recorded and
      identified. Depending on their level of severity and duration, depurative
      practices can be classified as mild or strict. The wide range of medicinal uses
      reported supports both the involvement of adaptive stress responses in depurative
      practices and the consideration of the plants employed in this practices as
      medicinal stressors. CONCLUSIONS: By inducing moderate stress within safe levels,
      depurative practices in Chazuta could produce adaptive responses that would
      protect against the detrimental consequences of chronic stress and stress-related
      diseases. This hypothesis could help to understand the diversity of the medicinal
      uses recorded in the field. Thus, plant remedies used in these practices in
      Chazuta could be considered as "medicinal stressors" as through vomiting the
      necessary neuroendocrine stress activation would be produced. In addition, other
      bioactivities that plants may harbour could converge with the whole stress
      reactivity process.

PMID- 23123267
TI  - Prophylactic effects of Orthosiphon stamineus Benth. extracts on experimental
      induction of calcium oxalate nephrolithiasis in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Orthosiphon stamineus (OS) popularly known as
      "diuretic agent" are traditionally used in folk medicine in the treatment of
      hyperuricemia, rheumatism, gout, nephritis, nephrolithiasis, urethritis and
      cystitis. AIM OF THE STUDY: To evaluate prophylactic potentials of total
      flavonoids, total phenolics and polysaccharides from OS on experimental induction
      of calcium oxalate (CaOx) nephrolithiasis in rats. MATERIALS AND METHODS:
      Nephrolithic rats were induced by treating with 1.0% ethylene glycol and 1.0%
      ammonium chloride for 7 days. Rats in the treated groups were also given OS
      extracts at the doses of 80 mg/kg and 160 mg/kg. Urine samples (4h) and serum
      samples were collected at 7th day for biochemical analysis. Kidney tissues were
      stained with H.E. and analyzed by light microscopy. Expressions of OPN protein
      were detected by immunohistochemistry. Rates of nucleation and aggregation of
      calcium oxalate crystals were derived from 20-min time-course measurements of
      optic density at 620 nm after mixing solutions containing calcium chloride,
      sodium oxalate and OS extracts at 37 degrees C, pH 5.7. RESULTS: Polysaccharides
      exhibited the most significant prophylactic effects by reversing BUN and S(cr)
      levels, ameliorating histopathological changes, increasing urine C(2)O(4)(2-) and
      Ca(2+) excretion and down-regulating OPN protein expression of kidney in the
      model rats in comparison with those effects of total flavonoids and total
      phenolics. Polysaccharides could also significantly inhibit both nucleation and
      aggregation of CaOx crystals. CONCLUSIONS: Polysaccharides were the main
      therapeutic materials in OS. It had impressive prophylactic effects on CaOx
      stones in nephrolithic rats, playing a role as a regulator of OPN protein
      expression to increase urine C(2)O(4)(2-) and Ca(2+) excretion and also as an
      inhibitor of CaOx crystallization.

PMID- 23123269
TI  - Anti-inflammatory and antinociceptive activities of Campomanesia adamantium.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Campomanesia species are used in folk medicine as
      anti-inflammatory, anti-rheumatic, anti-diarrheal and hypocholesterolemic. AIM OF
      THE STUDY: The present study investigated the in vivo anti-inflammatory and
      antinociceptive properties of ethyl acetate (AE) and aqueous (Aq) extracts from
      leaves of Campomanesia adamantium and in vitro anti-inflammatory activity of AE
      and its isolated flavonols, myricitrin and myricetin. MATERIALS AND METHODS: The
      antinociceptive activity of AE and Aq was evaluated using acetic acid-induced
      writhing and formalin methods. The in vivo anti-inflammatory effect of AE and Aq
      was evaluated using carrageenan-induced paw oedema in mice. AE, myricitrin and
      myricetin were evaluated for their abilities to modulate the production of NO,
      TNF-alpha and IL-10 in LPS/IFN-gamma stimulated J774.A1 macrophages. RESULTS: It
      was found that orally administrated AE and Aq (125 and 250 mg/kg) inhibited
      carrageenan-induced paw oedema in mice. AE (125 and 250 mg/kg) and Aq (125 mg/kg)
      reduced the time to licking at the second phase of the formalin method in vivo in
      mice. AE (250 mg/kg) and Aq (125 mg/kg) also reduced the number of writhes. AE,
      myricitrin and myricetin inhibited NO (320 MUg/mL and 6.25-100 MUM, respectively)
      and TNF-alpha production by macrophages (320 MUg/mL for AE, 100 MUM for
      myricitrin and 25-100 MUM for myricetin). AE (160 and 320 MUg/mL), myricitrin (50
      and 100 MUM) and myricetin (25-100 MUM) increased IL-10 production by
      macrophages. CONCLUSIONS: The ethyl acetate and aqueous extracts from
      Campomanesia adamantium showed antinociceptive and anti-inflammatory effects
      supporting the use of the plant in folk medicine. The results suggest that anti
      oedematogenic effect promoted by aqueous extract involves several anti
      inflammatory mechanisms of action. The antinociceptive effect shown by aqueous
      extract can be due to the modulation of release of inflammatory mediators
      involved in nociception. The anti-inflammatory effects of AE and of its isolated
      flavonols may be attributed to inhibition of pro-inflammatory cytokines
      production, TNF-alpha and NO and to the increased of IL-10 production.

PMID- 23123271
TI  - Secondary osteon size and collagen/lamellar organization ("osteon morphotypes")
      are not coupled, but potentially adapt independently for local strain mode or
      magnitude.
AB  - In bone, matrix slippage that occurs at cement lines of secondary osteons during
      loading is an important toughening mechanism. Toughness can also be enhanced by
      modifications in osteon cross-sectional size (diameter) for specific load
      environments; for example, smaller osteons in more highly strained "compression"
      regions vs. larger osteons in less strained "tension" regions. Additional osteon
      characteristics that enhance toughness are distinctive variations in
      collagen/lamellar organization (i.e., "osteon morphotypes"). Interactions might
      exist between osteon diameter and morphotype that represent adaptations for
      resisting deleterious shear stresses that occur at the cement line. This may be
      why osteons often have a peripheral ring (or "hoop") of highly oblique/transverse
      collagen. We hypothesized that well developed/distinct "hoops" are compensatory
      adaptations in cases where increased osteon diameter is mechanically advantageous
      (e.g., larger osteons in "tension" regions would have well developed/distinct
      "hoops" in order to resist deleterious consequences of co-existing localized
      shear stresses). We tested this hypothesis by determining if there are
      correlations between osteon diameters and strongly hooped morphotypes in
      "tension", "compression", and "neutral axis" regions of femora (chimpanzees,
      humans), radii (horse, sheep) and calcanei (horse, deer). The results reject the
      hypothesis-larger osteons are not associated with well developed/distinct
      "hoops", even in "tension regions" where the effect was expected to be obvious.
      Although osteon diameter and morphotype are not coupled, osteon diameters seem to
      be associated with increased strain magnitudes in some cases, but this is
      inconsistent. By contrast, osteon morphotypes are more strongly correlated with
      the distribution of tension and compression.

PMID- 23123270
TI  - The crystallographic structure of Panicum Mosaic Virus (PMV).
AB  - The structure of Panicum Mosaic Virus (PMV) was determined by X-ray diffraction
      analysis to 2.9A resolution. The crystals were of pseudo symmetry F23; the true
      crystallographic unit cell was of space group P2(1) with a=411.7A, b=403.9A and
      c=412.5A, with beta=89.7 degrees . The asymmetric unit was two entire T=3 virus
      particles, or 360 protein subunits. The structure was solved by conventional
      molecular replacement from two distant homologues, Cocksfoot Mottle Virus (CfMV)
      and Tobacco Necrosis Virus (TNV), of ~20% sequence identity followed by phase
      extension. The model was initially refined with exact icosahedral constraints and
      then with icosahedral restraints. The virus has Ca(++) ions octahedrally
      coordinated by six aspartic acid residues on quasi threefold axes, which is
      completely different than for either CfMV or TNV. Amino terminal residues 1-53, 1
      49 and 1-21 of the A, B and C subunits, respectively, and the four C-terminal
      residues (239-242) are not visible in electron density maps. The additional
      ordered residues of the C chain form a prominent "arm" that intertwines with
      symmetry equivalent "arms" at icosahedral threefold axes, as was seen in both
      CfMV and TNV. A 17 nucleotide hairpin segment of genomic RNA is icosahedrally
      ordered and bound at 60 equivalent sites at quasi twofold A-B subunit interfaces
      at the interior surface of the capsid. This segment of RNA may serve as a
      conformational switch for coat protein subunits, as has been proposed for similar
      RNA segments in other viruses.

PMID- 23123273
TI  - Comparative analysis of Tritrichomonas foetus (Riedmuller, 1928) cat genotype, T.
      foetus (Riedmuller, 1928) cattle genotype and Tritrichomonas suis (Davaine, 1875)
      at 10 DNA loci.
AB  - The parasitic protists in the genus Tritrichomonas cause significant disease in
      domestic cattle and cats. To assess the genetic diversity of feline and bovine
      isolates of Tritrichomonas foetus (Riedmuller, 1928) Wenrich and Emmerson, 1933,
      we used 10 different genetic regions, namely the protein coding genes of cysteine
      proteases 1, 2 and 4-9 (CP1, 2, 4-9) involved in the pathogenesis of the disease
      caused by the parasite. The cytosolic malate dehydrogenase 1 (MDH1) and internal
      transcribed spacer region 2 of the rDNA unit (ITS2) were included as additional
      markers. The gene sequences were compared with those of Tritrichomonas suis
      (Davaine, 1875) Morgan and Hawkins, 1948 and Tritrichomonas mobilensisCulberson
      et al., 1986. The study revealed 100% identity for all 10 genes among all feline
      isolates (=T. foetus cat genotype), 100% identity among all bovine isolates (=T.
      foetus cattle genotype) and a genetic distinctness of 1% between the cat and
      cattle genotypes of T. foetus. The cattle genotype of T. foetus was 100%
      identical to T. suis at nine loci (CP1, 2, 4-8, ITS2, MDH1). At CP9, three out of
      four T. suis isolates were identical to the T. foetus cattle genotype, while the
      T. suis isolate SUI-H3B sequence contained a single unique nucleotide
      substitution. Tritrichomonas mobilensis was 0.4% and 0.7% distinct from the cat
      and cattle genotypes of T. foetus, respectively. The genetic differences resulted
      in amino acid changes in the CP genes, most pronouncedly in CP2, potentially
      providing a platform for elucidation of genotype-specific host-pathogen
      interactions of T. foetus. On the basis of this data we judge T. suis and T.
      foetus to be subjective synonyms. For the first time, on objective nomenclatural
      grounds, the authority of T. suis is given to Davaine, 1875, rather than the
      commonly cited Gruby and Delafond, 1843. To maintain prevailing usage of T.
      foetus, we are suppressing the senior synomym T. suisDavaine, 1875 according to
      Article 23.9, because it has never been used as a valid name after 1899 and T.
      foetus is widely discussed as the cause of bovine trichomonosis. Thus bovine,
      feline and porcine isolates should all be given the name T. foetus. This promotes
      the stability of T. foetus for the veterinary and economically significant
      venereal parasite causing bovine trichomonosis.

PMID- 23123272
TI  - Impact of a carbohydrate-electrolyte drink on ingestive behaviour, affect and
      self-selected intensity during recreational exercise after 24-h fluid
      restriction.
AB  - This study examined the effects of a carbohydrate-electrolyte drink on voluntary
      fluid intake, affect and self-selected intensity during recreational exercise
      after fluid restriction. In a randomised counterbalanced design, ten physically
      active adults were dehydrated via a 24-h period of fluid restriction before
      completing two 20-min bouts of cardiovascular exercise, 20-min of resistance
      exercise and 20 min on a cycle ergometer at a self-selected intensity with ad
      libitum access to water (W) or a carbohydrate-electrolyte solution (CES). Fluid
      restriction induced hypohydration of ~1.2% initial body mass. Fluid intake during
      exercise was greater with CES (2105 +/- 363 vs. 1470 +/- 429 mL; P<0.01) and
      resulted in more adequate hydration (-0.03 +/- 0.65 vs. -1.26 +/- 0.80%; P<0.01).
      Plasma glucose concentrations (4.48 +/- 0.40 vs. 4.28 +/- 0.32 mmol L(-1);
      P<0.01) and pleasure ratings (2.63 +/- 1.17 vs. 1.81 +/- 1.37; P<0.01) were
      greater with CES than W. Mean power output during exercise performed at a self
      selected intensity was 5.6% greater with CES (171 +/- 63 vs. 162 +/- 60 W;
      P<0.05). In physically active adults performing a 'real-life' recreational
      exercise simulation, CES resulted in more adequate hydration and an enhanced
      affective experience that corresponded with an increase in self-selected exercise
      intensity.

PMID- 23123274
TI  - Reduced cognitive function in children with toxocariasis in a nationally
      representative sample of the United States.
AB  - Toxocariasis has recently been recognised as a potentially important neglected
      infection in developed countries, particularly those that experience substantive
      health disparities such as the United States. Given a relatively high prevalence
      of infection, an association between Toxocara infection and cognitive function
      may elucidate an important mechanism by which toxocariasis could contribute
      significantly to morbidity while still remaining hidden and, thus, neglected. To
      assess the potential relationship between toxocariasis and cognitive function,
      this investigation measured differences in components of both the Wechsler
      Intelligence Scale for Children-Revised (WISC-R) and the Wide Range Achievement
      Test-Revised (WRAT-R) in children seropositive and in children seronegative for
      Toxocara antibodies in the Third National Health and Nutrition Examination
      Survey, a large, nationally-representative survey of the United States
      population. Seropositive children scored significantly lower on the WISC-R and
      WRAT-R compared with the seronegative children. Moreover, this relationship was
      independent of socioeconomic status, ethnicity, gender, rural residence,
      cytomegalovirus infection and blood lead levels. These results identify an
      important association that may reflect morbidity attributable to a genuine
      neglected infection. Nevertheless, longitudinal data are required to confirm an
      etiological connection between toxocariasis and cognitive function, as well as
      the true population attributable risk for toxocariasis and its chronic sequelae.

PMID- 23123275
TI  - Structural basis of MET receptor dimerization by the bacterial invasion protein
      InlB and the HGF/SF splice variant NK1.
AB  - The structural basis of ligand-induced dimerization of the receptor tyrosine
      kinase MET by its natural ligand hepatocyte growth factor/scatter factor (HGF/SF)
      is not well understood. However, interesting insight into the molecular mechanism
      of MET dimerization has emerged from crystal structures of MET in complex with a
      bacterial agonist, the invasion protein internalin B (InlB) from pathogenic
      Listeria monocytogenes. MET activation by InlB promotes uptake of bacteria into
      host cells. Structural and biophysical data suggest that InlB is monomeric on its
      own but dimerizes upon binding to the membrane-anchored MET receptor promoting
      the formation of a signaling active 2:2 complex. The dimerization interface is
      small and unusually located on the convex side of the curved InlB leucine-rich
      repeat (LRR) domain. As InlB does not dimerize in solution, the dimerization site
      could only be identified by studying packing contacts of InlB in various crystal
      forms and had to be proven by scrutinizing its biological relevance in cellular
      assays. InlB dimerization is thus an example of a low-affinity contact that
      appears irrelevant in solution but becomes physiologically significant in the
      context of 2-dimensional diffusion restricted to the membrane plane. The
      resulting 2:2 InlB:MET complex has an InlB dimer at its center with one MET
      molecule bound peripherally to each InlB. This model of ligand-mediated MET
      dimerization may serve as a blue-print to understand MET activation by NK1, a
      naturally occurring HGF/SF splice variant and MET agonist. Crystal structures of
      NK1 repeatedly show a NK1 dimer, in which residues implicated in MET-binding are
      located on the outside. Thus, MET dimerization by NK1 may also be ligand-mediated
      with a NK1 dimer at the center of the 2:2 complex with one MET molecule bound
      peripherally to each NK1. This article is part of a Special Issue entitled:
      Emerging recognition and activation mechanisms of receptor tyrosine kinases. 

PMID- 23123276
TI  - Creating diseases to understand what prevents them: genetic analysis of
      inflammation in the gastrointestinal tract.
AB  - Inflammatory bowel diseases (IBD), including both ulcerative colitis and Crohn's
      disease, are extremely variable in severity and have strong genetic components.
      In mice, several mutations are known to favor or inhibit intestinal inflammation.
      But a comprehensive picture of the pathogenesis of IBD cannot be assembled based
      on the limited information so far available from mouse genetic analyses, nor can
      human IBD be stringently ascribed to mutations known to be influential in mice.
      This review highlights recent progress made using mouse models created through a
      forward genetic approach towards the understanding of genes that normally prevent
      intestinal inflammation.

PMID- 23123278
TI  - Allergic responses in the lung and skin: new players in the game.

PMID- 23123277
TI  - Developing connections amongst key cytokines and dysregulated germinal centers in
      autoimmunity.
AB  - Systemic autoimmunity owing to overactivity of Tfh and dysregulated germinal
      centers has been described in mice and humans. Cytokines such as IL-21, IFN
      gamma, IL-6 and IL-17 are elevated in the plasma of mouse models of lupus,
      arthritis, and multiple sclerosis, and in subsets of patients with autoimmune
      disease. Monoclonal antibodies targeting these cytokines are entering clinical
      trials. While these cytokines exert pleiotropic effects on immune cells and
      organs, it is becoming clear that each and all of them can profoundly regulate
      Tfh numbers and/or function and induce or maintain the aberrant germinal center
      reactions that lead to pathogenic autoantibody formation. Here we review recent
      discoveries into the roles of IL-21, IFN-gamma, IL-6, and IL-17 in germinal
      center responses and antibody-driven autoimmunity. These new insights used in
      conjunction with biomarkers of an overactive Tfh pathway may help stratify
      patients to rationalize the use of emerging monoclonal anti-cytokine antibody
      therapies.

PMID- 23123279
TI  - Autoimmunity.

PMID- 23123280
TI  - Health plan paid cost of epilepsy in 2009 in the U.S.
AB  - Our objectives were to estimate the health plan paid cost of epilepsy and to show
      major cost driver(s) of these costs. The health insurance claims and membership
      data from six U.S. health plans were analyzed. To prepare two comparison groups,
      individuals with epilepsy (n=5810) were match-paired with individuals without
      epilepsy (n=5810) using propensity scores derived from logistic regression using
      gender, age group, health plan product, and length of enrollment in the health
      plans. Total health plan paid cost per member per year (PMPY) was $11,232 for the
      epilepsy group and $3026 for the controls (p<0.001). The estimated cost PMPY for
      treatment of epilepsy was $8206. Relative distribution (%) of health plan paid
      costs ($) by cost driver category based on place of service (POS) indicated that
      the treatment of epilepsy places a larger cost burden in inpatient POS than in
      outpatient hospital or MD office POS compared to controls.

PMID- 23123281
TI  - Feasibility of focal transcranial DC polarization with simultaneous EEG
      recording: preliminary assessment in healthy subjects and human epilepsy.
AB  - We aimed to investigate the feasibility of an experimental system for
      simultaneous transcranial DC stimulation (tDCS) and EEG recording in human
      epilepsy. We report tolerability of this system in a cross-over controlled trial
      with 15 healthy subjects and preliminary effects of its use, testing repeated
      tDCS sessions, in two patients with drug-refractory Continuous Spike-Wave
      Discharges During Slow Sleep (CSWS). Our system combining continuous recording of
      the EEG with tDCS allows detailed evaluation of the interictal activity during
      the entire process. Stimulation with 1 mA was well-tolerated in both healthy
      volunteers and patients with refractory epilepsy. The large reduction in
      interictal epileptiform EEG discharges in the two subjects with epilepsy supports
      further investigation of tDCS using this combined method of stimulation and
      monitoring in epilepsy. Continuous monitoring of epileptic activity throughout
      tDCS improves safety and allows detailed evaluation of epileptic activity changes
      induced by tDCS in patients.

PMID- 23123282
TI  - [Preoperative imaging of deeply infiltrating endometriosis in: Transvaginal
      sonography, rectal endoscopic sonography and magnetic resonance imaging].
AB  - OBJECTIVES: Compare the accuracy of transvaginal ultrasonography (TVUS), rectal
      endoscopic sonography (RES), and magnetic resonance imaging (MRI) before deeply
      infiltrating endometriosis surgery. PATIENTS AND METHODS: A retrospective study
      with 25 deeply endometriosis patients underwent the three imaging examinations
      before surgery. Calculation of sensitivity, specificity, positive predictive
      value, negative predictive value and accuracy for the different locations:
      ovaries, uterosacral ligaments and torus, rectovaginal septum, rectosigmoid
      junction, bladder. RESULTS: Ovarian and deep pelvic endometriosis was found in
      surgery and confirmed by histology in all patients. Sensitivity and specificity
      are respectively: for ovaries: 88.2% and 71% of TVUS; 80% and 81.2% of RES; 87.5%
      and 71% of MRI. For uterosacral ligaments: 63% and 82,6% of TVUS; 37% and 100% of
      RES; 69% and 82.6% of MRI. For torus: 57.1% and 100% of TVUS; 76.2% and 100% of
      RES; 76.2% and 100% of MRI. For rectovaginal septum: 63.2% and 100% for TVUS;
      89.5% and 66.7% of EER; 47.4% and 100% of MRI. For rectosigmoid junction: 73.7%
      and 66.7% of TVUS; 94.7% and 66.7% of RES; 89.5% and 50% of MRI. For bladder:
      16.7% and 100% of TVUS; 16.7% and 100% of RES; 33.3% and 89.5% of MRI. DISCUSSION
      AND CONCLUSION: We found that TVUS is the more performant for endometriomas, it
      is MRI for torus, uterosacral ligaments and little bladder lesions, RES for
      rectovaginal septum and rectosigmoid junction. So in the clinical practice, the
      three imaging examinations are complementary for the preoperative assessment of
      deeply endometriosis.

PMID- 23123283
TI  - Developmental changes of calretinin immunoreactivity in the anterior thalamic
      nuclei of the guinea pig.
AB  - This study describes for the first time the distribution of the calcium-binding
      protein calretinin (CR) in the anterior thalamic nuclei (ATN) of the guinea pig
      during development. Brains from animals ranging from 40th embryonic day (E40) to
      80th postnatal day (P80) were used in the study. No CR-immunoreactive (CR-ir)
      perikarya were present among the ATN at E40, but thick bundles of fibers
      containing CR were crossing the anteromedial nucleus (AM). The first CR-ir
      neurons appeared at E50 in the lateral part of the AM. At E60, the bundles of
      fibers disappeared and the whole area of AM displayed closely packed CR-ir
      perikarya. At this stage, CR also appeared in neurons of the anteroventral
      nucleus (AV), particularly in its lateral part and along its dorsal border.
      Moreover, from E50 short and thin bundles of fibers were observed in the medial
      part of the AV. The ATN of newborns (P0) already showed an adult-like CR
      distribution pattern - perikarya in the AM and AV were distributed more
      homogenously and their number was slightly decreased in comparison to E60. The
      anterodorsal nucleus (AD) was devoid of CR-ir neurons in all studied stages. In
      conclusion, our results demonstrate that calretinin appears for the first time in
      neurons of various anterior thalamic nuclei of the guinea pig between 40th and
      60th day of prenatal development.

PMID- 23123284
TI  - The role of calcitonin gene-related peptide on the increase in transient receptor
      potential vanilloid-1 levels in trigeminal ganglion and trigeminal nucleus
      caudalis activation of rat.
AB  - Calcitonin gene-related peptide (CGRP) and transient receptor potential vanilloid
      1 (TRPV1) play an important role in the development of pain and migraine
      pathogenesis. Increase in plasma CGRP levels is associated with delayed migraine
      like attacks in migraine patients. Although several lines of evidence have
      indicated a key role of CGRP in migraine pain, its mechanisms remain unclear. In
      this study, we aimed to investigate the functional role of CGRP on trigeminal
      nociceptive pathway by determining the alteration in TRPV1 levels in trigeminal
      ganglion (TG) and the activation of trigeminal nucleus caudalis (TNC) of rat.
      Post intravenous injection of CGRP (600ng/kg) at 60min significantly increased
      the levels of TRPV1, CGRP, phosphorylated protein kinase C and phosphorylated
      cyclic AMP responsive element-binding protein in TG of rats. The number of small
      and medium TRPV1 and CGRP positive immunostaining neurons accompanying with co
      localization of TRPV1 with CGRP neurons were significantly increased in TG of
      CGRP-injected rats. The sustained increase in c-Fos expression in TNC neurons was
      also observed in CGRP-injected rats. These results indicate that CGRP may
      participate in trigeminal nociceptive system sensitization by induced increase in
      TRPV1 and CGRP levels in TG neurons and activation of the central neurons in TNC.

PMID- 23123285
TI  - The restricted ovulator chicken strain: an oviparous vertebrate model of
      reproductive dysfunction caused by a gene defect affecting an oocyte-specific
      receptor.
AB  - A unique non-laying strain of chickens with heritable hyperlipidemia and aortic
      atherosclerosis was first described in 1974. Subsequent work established that the
      phenotype results from a naturally occurring point mutation in the gene
      specifying the very low density lipoprotein (VLDL) receptor, a 95-kDa membrane
      protein which normally mediates the massive uptake of the main circulating
      hepatically-synthesized yolk precursors, VLDL and vitellogenin. As a result, hens
      of the mutant strain termed "restricted ovulator" (R/O) have approximately 5-fold
      elevations in circulating cholesterol and triglyceride concentrations compared
      with normal layers, and hepatic lipogenesis and cholesterogenesis are markedly
      attenuated due to feedback inhibition. R/O hens also exhibit hyperestrogenemia,
      hypoprogesteronemia, elevated circulating gonadotropins, and up-regulated
      pituitary progesterone receptor mRNA and isoforms. The ovaries of R/O hens are
      abnormal in that they lack a follicular hierarchy and contain many small
      preovulatory follicles of various colors, shapes, and sizes. However, since R/O
      hens occasionally lay eggs, it is possible that endocytic receptors other than
      the VLDL receptor may be able to facilitate oocyte growth and/or that yolk
      precursor uptake can occur via a nonspecific bulk process. A mammalian model of
      impaired fecundity with abnormal lipoprotein metabolism also has been described,
      but different mechanisms are likely responsible for its reproductive dysfunction.
      Nevertheless, as our understanding of the molecular physiology and biochemistry
      of avian oocyte growth continues to expand, in part due to studies of the R/O
      model, new analogies may emerge between avian and mammalian systems, which
      ultimately could help to answer important questions in reproductive biology.

PMID- 23123286
TI  - Comparative metal distribution in scalp hair of Pakistani and Irish referents and
      diabetes mellitus patients.
AB  - BACKGROUND: The essential metals, chromium (Cr), magnesium (Mg), manganese (Mn)
      and zinc (Zn), are necessary for many metabolic processes and their homeostasis
      is crucial for life. The toxic metals, cadmium (Cd) and lead (Pb), have no
      beneficial role in human metabolism. The aim of this study was to investigate the
      levels of Cd, Cr, Mg, Mn, Pb, and Zn in scalp hair samples of type 2 diabetes
      mellitus patients of both genders, ages ranging from 30 to 50 y, and belong to
      urban areas of Ireland and Pakistan. For comparison purposes, age matched non
      diabetic subjects of both countries were selected as referents. METHODS: The
      concentrations of metals in scalp hair samples were measured by inductively
      coupled plasma atomic emission spectrophotometer and atomic absorption
      spectrophotometer after microwave-assisted acid digestion. The validity and
      accuracy of the methodology were checked by conventional wet-acid-digestion
      method and using certified reference materials. RESULTS: The mean values of Cd
      and Pb were significantly higher in scalp hair samples of both Pakistani and
      Irish diabetic patients as compared to referents of both countries (P<0.001). In
      contrast, lower Cr, Mg, Mn, and Zn (P<0.01) concentrations were detected in scalp
      hair derived from patients with type 2 diabetes versus healthy subjects of both
      countries. CONCLUSION: This study showed that, increased toxic elements and
      decreased essential elements are associated with diabetes mellitus. Therefore,
      these elements may play a role in the development and pathogenesis of diabetes
      mellitus.

PMID- 23123287
TI  - Novel antilithiatic cationic proteins from human calcium oxalate renal stone
      matrix identified by MALDI-TOF-MS endowed with cytoprotective potential: an
      insight into the molecular mechanism of urolithiasis.
AB  - BACKGROUND: No substantial work has been conducted to date in context to cationic
      proteins with antilithiatic activity. We explored the antilithiatic cationic
      proteins present in human calcium oxalate (CaOx) stones and also examined their
      molecular interactions with calcium oxalate crystals in silico. METHODS: Proteins
      were isolated from the matrix of human CaOx containing kidney stones. Proteins
      having MW>3 kDa were subjected to cation exchange chromatography followed by
      molecular-sieve chromatography. The effect of these purified cationic proteins
      was tested against CaOx nucleation and growth and on oxalate injured MDCK cells
      for their activity. Proteins were identified by MALDI-TOF MS. Molecular
      interaction studies with COM crystals in silico were also investigated. RESULTS:
      Three antilithiatic cationic proteins were identified as histone-lysine N
      methyltransferase, inward rectifier K channel and protein Wnt-2 (MW~53, ~44, and
      ~42 kDa respectively) by MALDI-TOF MS based on database search with MASCOT
      server. Further molecular modeling calculations revealed the mode of interaction
      of these proteins with CaOx at the molecular level. CONCLUSION: We identified
      histone-lysine N-methyltransferase, inward rectifier K channel and protein Wnt-2
      as novel antilithiatic proteins which play a vital role in the kidney function
      and have been associated with various kidney diseases.

PMID- 23123288
TI  - Enhanced submerged membrane bioreactor combined with biosurfactant rhamnolipids:
      performance for frying oil degradation and membrane fouling reduction.
AB  - In this study, a novel submerged membrane bioreactor (SMBR) combined with
      rhamnolipids was developed to treat frying oil wastewater and control the problem
      of membrane fouling. To validate the feasibility of this new design, a hybrid
      SMBR with additional rhamnolipids (RSMBR) and a controlled SMBR (CSMBR) were run
      in parallel. Results demonstrated that RSMBR not only held high removal
      efficiency of oil up to 90% at short hydraulic time, but also exhibited 10 times
      higher membrane permeability in comparison to CSMBR. The presence of rhamnolipids
      greatly enhanced the contact and reaction between the microorganism and oil
      molecules. The great improvement in membrane filterability was associated with an
      increase in hydrophobicity of flocs as well as the increase of particle size from
      53.06 to 145.54 MUm. The oil strongly adhered to the surface of flocs by
      rhamnolipids, and consequently prevented larger oil droplets directly depositing
      on the membrane surface.

PMID- 23123289
TI  - Methodological streamlining of SNP discovery and genotyping via high-resolution
      melting analysis (HRMA) in non-model species.
AB  - The exponential growth of genetic resources is fueled by continued advances in
      genomic technologies and the adoption of single nucleotide polymorphisms (SNPs)
      for population studies. Concomitant to these developments, there is growing need
      for rapid screening and subsequent genotyping of SNPs in non-model organisms.
      Here we provide a rapid and low-cost workflow utilizing high-resolution melting
      analysis (HRMA) for nuclear marker development and genotyping of 774 Atlantic and
      Mediterranean swordfish (Xiphias gladius) that is amendable to other species.
      Preliminary HRMA screening of amplicons (>290bp) for 10 nuclear loci revealed the
      presence of nucleotide polymorphisms, however, length and variability precluded
      diagnostic genotyping. Two variants of HRMA were therefore utilized to provide
      diagnostic genotyping assays. Short-amplicon HRMA (SA-HRMA), in which primers
      flank closely a SNP of interest, was identified as a low cost, rapid, closed-tube
      diagnostic genotyping assay that could distinguish between homozygous genotypes
      by DeltaTm, and heterozygous genotypes by heteroduplex melting curve profiles.
      When the patterns of sequence variation were not suitable for SA-HRMA, unlabeled
      probe (UP)-HRMA was utilized. UP-HRMA has the advantage of being capable of
      genotyping multiple linked SNPs in a single closed-tube assay without Bayesian
      haplotype reconstruction, and can identify new SNPs while genotyping populations.
      Almost 37% of the SNPs genotyped via UP-HRMA were discovered while genotyping
      populations and not from preliminary screening. Analysis of swordfish in the
      North Atlantic (NA, n=419), South Atlantic (SA, n=296), and Mediterranean (MED,
      n=59) found no significant linkage disequilibrium. To assess whether deviations
      in HWE could be the result of genotyping error rather than population admixture
      only swordfish from reported spawning areas in the NA (n=49), MED (n=59), and SA
      (n=42) were analyzed and all loci were in Hardy-Weinberg equilibrium. Significant
      genetic differentiation (P<0.001) was identified among populations. 

PMID- 23123290
TI  - Cardiac myosin isoforms exhibit differential rates of MgADP release and MgATP
      binding detected by myocardial viscoelasticity.
AB  - We measured myosin crossbridge detachment rate and the rates of MgADP release and
      MgATP binding in mouse and rat myocardial strips bearing one of the two cardiac
      myosin heavy chain (MyHC) isoforms. Mice and rats were fed an iodine-deficient,
      propylthiouracil diet resulting in ~100% expression of beta-MyHC in the
      ventricles. Ventricles of control animals expressed ~100% alpha-MyHC. Chemically
      skinned myocardial strips prepared from papillary muscle were subjected to
      sinusoidal length perturbation analysis at maximum calcium activation pCa 4.8 and
      17 degrees C. Frequency characteristics of myocardial viscoelasticity were used
      to calculate crossbridge detachment rate over 0.01 to 5mM [MgATP]. The rate of
      MgADP release, equivalent to the asymptotic value of crossbridge detachment rate
      at high MgATP, was highest in mouse alpha-MyHC (111.4+/-6.2s(-1)) followed by rat
      alpha-MyHC (65.0+/-7.3s(-1)), mouse beta-MyHC (24.3+/-1.8s(-1)) and rat beta-MyHC
      (15.5+/-0.8s(-1)). The rate of MgATP binding was highest in mouse alpha-MyHC
      (325+/-32 mM(-1) s(-1)) then mouse beta-MyHC (152+/-23 mM(-1) s(-1)), rat alpha
      MyHC (108+/-10 mM(-1) s(-1)) and rat beta-MyHC (55+/-6 mM(-1) s(-1)). Because the
      events of MgADP release and MgATP binding occur in a post power-stroke state of
      the myosin crossbridge, we infer that MgATP release and MgATP binding must be
      regulated by isoform- and species-specific structural differences located outside
      the nucleotide binding pocket, which is identical in sequence for these four
      myosins. We postulate that differences in the stiffness profile of the entire
      myosin molecule, including the thick filament and the myosin-actin interface, are
      primarily responsible for determining the strain on the nucleotide binding pocket
      and the subsequent differences in the rates of nucleotide release and binding
      observed among the four myosins examined here.

PMID- 23123291
TI  - Mapping biological behaviors by application of longer-lived positron emitting
      radionuclides.
AB  - With the technological development of positron emission tomography (PET) and the
      advent of novel antibody-directed drug delivery systems, longer-lived positron
      emitting radionuclides are moving to the forefront to take important roles in
      tracking the distribution of biotherapeutics such as antibodies, and for
      monitoring biological processes and responses. Longer half-life radionuclides
      possess advantages of convenient on-site preparation procedures for both clinical
      and non-clinical applications. The suitability of the long half-life
      radionuclides for imaging intact monoclonal antibodies (mAbs) and their
      respective fragments, which have inherently long biological half-lives, has
      attracted increased interest in recent years. In this review, we provide a survey
      of the recent literature as it applies to the development of nine-selected longer
      lived positron emitters with half-lives of 9-140h (e.g., (124)I, (64)Cu, (86)Y
      and (89)Zr), and describe the biological behaviors of radionuclide-labeled mAbs
      with respect to distribution and targeting characteristics, potential toxicities,
      biological applications, and clinical translation potentials. 

PMID- 23123292
TI  - Nanoparticles for oral delivery: targeted nanoparticles with peptidic ligands for
      oral protein delivery.
AB  - As the field of biotechnology has advanced, oral protein delivery has also made
      significant progress. Oral delivery is the most common method of drug
      administration with high levels of patient acceptance. Despite the preference of
      oral delivery, administration of therapeutic proteins has been extremely
      difficult. Increasing the bioavailability of oral protein drugs to the
      therapeutically acceptable level is still a challenging goal. Poor membrane
      permeability, high molecular weight, and enzymatic degradation of protein drugs
      have remained unsolved issues. Among diverse strategies, nanotechnology has
      provided a glimpse of hope in oral delivery of protein drugs. Nanoparticles have
      advantages, such as small size, high surface area, and modification using
      functional groups for high capacity or selectivity. Nanoparticles with peptidic
      ligands are especially worthy of notice because they can be used for specific
      targeting in the gastrointestinal (GI) tract. This article reviews the transport
      mechanism of the GI tract, barriers to protein absorption, current status and
      limitations of nanotechnology for oral protein delivery system.

PMID- 23123295
TI  - New forms of superparamagnetic nanoparticles for biomedical applications.
AB  - Magnetic nanoparticles (MNPs) based on iron oxide, especially magnetite (Fe3O4),
      have been explored as sensitive probes for magnetic resonance imaging and
      therapeutic applications. Such application potentials plus the need to achieve
      high efficiency and sensitivity have motivated the search for new forms of
      superparamagnetic NPs with additional chemical and physical functionalities. This
      review summarizes the latest development of high moment MNPs, multifunctional
      MNPs, and porous hollow MNPs for biosensing, molecular imaging, and drug delivery
      applications.

PMID- 23123296
TI  - Epidemiology of African swine fever virus.
AB  - African swine fever virus used to occur primarily in Africa. There had been
      occasional incursions into Europe or America which apart from the endemic
      situation on the island of Sardinia always had been successfully controlled. But
      following an introduction of the virus in 2007, it now has expanded its
      geographical distribution into Caucasus and Eastern Europe where it has not been
      controlled, to date. African swine fever affects domestic and wild pig species,
      and can involve tick vectors. The ability of the virus to survive within a
      particular ecosystem is defined by the ecology of its wild host populations and
      the characteristics of livestock production systems, which influence host and
      vector species densities and interrelationships. African swine fever has high
      morbidity in naive pig populations and can result in very high mortality. There
      is no vaccine or treatment available. Apart from stamping out and movement
      control, there are no control measures, thereby potentially resulting in extreme
      losses for producers. Prevention and control of the infection requires good
      understanding of its epidemiology, so that targeted measures can be instigated.

PMID- 23123297
TI  - Advanced EEG analysis using threshold-free cluster-enhancement and non-parametric
      statistics.
AB  - Advances in EEG signal analysis and its combination with other investigative
      techniques make appropriate statistical analysis of large EEG datasets a crucial
      issue. With an increasing number of available channels and samples, as well as
      more exploratory experimental designs, it has become necessary to develop a
      statistical process with a high level of statistical integrity, signal
      sensitivity which nonetheless produces results which are interpretable to the
      common user. Threshold-free cluster-enhancement has recently been proposed as a
      useful analysis tool for fMRI datasets. This approach essentially takes into
      account both a data point's statistical intensity and neighbourhood to transform
      the original signal into a more intuitive understanding of 'real' differences
      between groups or conditions. Here we adapt this approach to optimally deal with
      EEG datasets and use permutation-based statistics to build an efficient
      statistical analysis. Furthermore we compare the results with several other non
      parametric and parametric approaches currently available using realistic
      simulated EEG signals. The proposed method is shown to be generally more
      sensitive to the variety of signal types common to EEG datasets without the need
      for any arbitrary adjusting of parameters. Moreover, a unique p-value is produced
      for each channel-sample pair such that specific questions can still be asked of
      the dataset while providing general information regarding the large-scale
      experimental effects.

PMID- 23123298
TI  - Helenalin-induced apoptosis is dependent on production of reactive oxygen species
      and independent of induction of endoplasmic reticulum stress in renal cell
      carcinoma.
AB  - Helenalin, a sesquiterpene lactone, exhibits anti-inflammatory and anti-tumor
      activities. Here, we investigated whether helenalin could induce apoptosis in
      human renal carcinoma Caki cells. Helenalin increased apoptosis in dose dependent
      manner in Caki cells, and also induced apoptosis in other carcinoma cells, such
      as human renal carcinoma ACHN cells, human colon carcinoma HT29 and HCT116 cells.
      We found that helenalin markedly induced endoplasmic reticulum (ER) stress
      related genes, such as regulated in development and DNA damage responses (REDD)
      1, activating transcription factor-4 (ATF4) and/or the CCAAT enhancer-binding
      protein-homologous protein (CHOP). However, down-regulation of ATF4 and/or CHOP
      expression by siRNA had no effect on helenalin-induced apoptosis in Caki and
      HCT116 cells. Helenalin increased production of intracellular reactive oxygen
      species (ROS). Furthermore, ROS scavengers, N-acetylcystine (NAC), and
      glutathione ethyl ester (GEE), reduced helenalin-induced apoptosis. Taken
      together, helenalin induced apoptosis via ROS generation in human renal carcinoma
      Caki cells.

PMID- 23123293
TI  - Mechanism of oral tolerance induction to therapeutic proteins.
AB  - Oral tolerance is defined as the specific suppression of humoral and/or cellular
      immune responses to an antigen by administration of the same antigen through the
      oral route. Due to its absence of toxicity, easy administration, and antigen
      specificity, oral tolerance is a very attractive approach to prevent unwanted
      immune responses that cause a variety of diseases or that complicate treatment of
      a disease. Many researchers have induced oral tolerance to efficiently treat
      autoimmune and inflammatory diseases in different animal models. However,
      clinical trials yielded limited success. Thus, understanding the mechanisms of
      oral tolerance induction to therapeutic proteins is critical for paving the way
      for clinical development of oral tolerance protocols. This review will summarize
      progress on understanding the major underlying tolerance mechanisms and
      contributors, including antigen presenting cells, regulatory T cells, cytokines,
      and signaling pathways. Potential applications, examples for therapeutic proteins
      and disease targets, and recent developments in delivery methods are discussed.

PMID- 23123294
TI  - Polymer-drug conjugates: origins, progress to date and future directions.
AB  - This overview focuses on bioconjugates of water-soluble polymers with low
      molecular weight drugs and proteins. After a short discussion of the origins of
      the field, the state-of-the-art is reviewed. Then research directions needed for
      the acceleration of the translation of nanomedicines into the clinic are
      outlined. Two most important directions, synthesis of backbone degradable polymer
      carriers and drug-free macromolecular therapeutics, a new paradigm in drug
      delivery, are discussed in detail. Finally, the future perspectives of the field
      are briefly discussed.

PMID- 23123299
TI  - Radiation therapy and cardiac rhythm devices: Should you relocate?

PMID- 23123300
TI  - Disseminated neoplasia in clams Venerupis aurea from Galicia (NW Spain):
      histopathology, ultrastructure and ploidy of the neoplastic cells, and comparison
      of diagnostic procedures.
AB  - This study reports evidence of a neoplastic disorder in the clam Venerupis aurea.
      In the first stage of the disease, masses of neoplastic cells were mainly
      observed in connective tissue of gills. These masses of neoplastic cells appeared
      more compact than in cases of disseminated neoplasia of other bivalve molluscs.
      As disease progresses, masses of abnormal cells were also observed in the
      connective tissue of all organs, thus alteration of vital functions in late stage
      is likely. The neoplastic cells had aneuploid DNA content, ranging from 1.6n to
      7.8 n. The ploidy level increased with the severity of the disease. A comparison
      of three light microscopy diagnostic procedures was performed. Histology was the
      most sensitive diagnostic test, whereas two different haematological techniques
      assayed presented unsatisfactory low levels of sensitivity. Specificity was high
      for the three assayed tests.

PMID- 23123302
TI  - Microinjection of melanin concentrating hormone into the lateral preoptic area
      promotes non-REM sleep in the rat.
AB  - The ventrolateral preoptic area (VLPO) has been recognized as one of the key
      structures responsible for the generation of non-REM (NREM) sleep. The melanin
      concentrating hormone (MCH)-containing neurons, which are located in the lateral
      hypothalamus and incerto-hypothalamic area, project widely throughout the central
      nervous system and include projections to the VLPO. The MCH has been associated
      with the central regulation of feeding and energy homeostasis. In addition,
      recent findings strongly suggest that the MCHergic system promotes sleep. The aim
      of the present study was to determine if MCH generates sleep by regulating VLPO
      neuronal activity. To this purpose, we characterized the effect of unilateral and
      bilateral microinjections of MCH into the VLPO on sleep and wakefulness in the
      rat. Unilateral administration of MCH into the VLPO and adjacent dorsal preoptic
      area did not modify sleep. On the contrary, bilateral microinjections of MCH (100
      ng) into these areas significantly increased light sleep (LS, 39.2+/-4.8 vs.
      21.6+/-2.5 min, P<0.05) and total NREM sleep (142.4+/-23.2 vs. 86.5+/-10.5 min,
      P<0.05) compared to control (saline) microinjections. No effect was observed on
      REM sleep. We conclude that MCH administration into the VLPO and adjacent dorsal
      lateral preoptic area promotes the generation of NREM sleep.

PMID- 23123304
TI  - Longitudinal zonation pattern in plant roots: conflicts and solutions.
AB  - Despite the relative simplicity of Arabidopsis root organization, there is no
      general agreement regarding the terminology used to describe the longitudinal
      zonation pattern (LZP) of this model system. In this opinion article, we examine
      inconsistencies in the terminology and provide a conceptual framework for the LZP
      that may be applied to all angiosperms. We propose that the root apical meristem
      (RAM) consists of the cell-proliferation domain where cells maintain a high
      probability to divide and the transition domain with a low probability of cell
      division; in both domains cells grow at the same, relatively low, rate. Owing to
      stochastic termination of cell proliferation in the RAM, the border between the
      domains is 'fuzzy'. Molecular markers analyzed together with quantitative growth
      and cell analyses could help to identify developmental zones along the root and
      lead to a better understanding of the LZP in angiosperms.

PMID- 23123301
TI  - Microstructured titanium regulates interleukin production by osteoblasts, an
      effect modulated by exogenous BMP-2.
AB  - Microtextured implant surfaces increase osteoblast differentiation in vitro and
      enhance bone-to-implant contact in vivo and clinically. These implants may be
      used in combination with recombinant human bone morphogenetic protein 2 (rhBMP-2)
      to enhance peri-implant bone formation. However, the effect of surface
      modifications alone or in combination with rhBMP-2 on the osteoblast-produced
      inflammatory microenvironment is unknown. MG63 cells were cultured on tissue
      culture polystyrene or titanium substrates: smooth pretreated (PT, Ra=0.2MUm),
      sandblasted/acid-etched (SLA, Ra=3.2MUm) or hydrophilic-SLA (modSLA). Expression
      and protein production of pro-inflammatory interleukins (IL1b, IL6, IL8, IL17)
      and anti-inflammatory interleukins (IL10) were measured in cells with or without
      rhBMP-2. To determine which BMP signaling pathways were involved, cultures were
      incubated with BMP pathway inhibitors to blockSmad (dorsomorphin), TAB/TAK1 ((5Z)
      7-oxozeaenol) or PKA (H-8) signaling. Culture on rough SLA and modSLA surfaces
      decreased pro-inflammatory interleukins and increased anti-inflammatory IL10.
      This effect was negated in cells treated with rhBMP-2, which caused an increase
      in pro-inflammatory interleukins and a decrease in anti-inflammatory interleukins
      through TAB/TAK signaling. The results suggest that surface microtexture
      modulates the inflammatory process during osseointegration, an effect that may
      enhance healing. However, rhBMP-2 in combination with microtextured titanium
      implants can influence the effect of cells on these surfaces, and may adversely
      affect cells involved in osseointegration.

PMID- 23123305
TI  - Effect of particle size, filler loadings and x-ray tube voltage on the
      transmitted x-ray transmission in tungsten oxide-epoxy composites.
AB  - The effect of particle size, filler loadings and x-ray tube voltage on the x-ray
      transmission in WO(3)-epoxy composites has been investigated using the
      mammography unit and a general radiography unit. Results indicate that nano-sized
      WO(3) has a better ability to attenuate the x-ray beam generated by lower tube
      voltages (25-35 kV) when compared to micro-sized WO(3) of the same filler
      loading. However, the effect of particle size on x-ray transmission was
      negligible at the higher x-ray tube voltages (40-120 kV).

PMID- 23123307
TI  - Teaching a systematic and evidence-based approach in an ambivalent context: a
      case example from Israel.
AB  - Systematically planned intervention (SPI) and evidence-based practice (EBP) have
      become widely known and influential concepts in Israeli social service
      administration and provision. Nevertheless, the lack of success in implementing
      SPI and EBP in the social work field has returned the discussion regarding its
      importance and development to social work scholars and educators. The following
      article presents a case example describing an attempt to build social workers'
      capacity to use SPI and EBP among graduate (Master level) Israeli social work
      students in a university-based practical workshop. A detailed description of
      contextual considerations and manifestations, alongside main teaching challenges
      and responses, general assessment of the attainment of the workshop's goals,
      concluding comments, and recommendations for SPI and EBP capacity builders are
      offered.

PMID- 23123308
TI  - Why do women pay more than they should? A mixed methods study of the
      implementation gap in a policy to subsidize the costs of deliveries in Burkina
      Faso.
AB  - In 2007, Burkina Faso launched a public policy to subsidize 80% of the cost of
      normal deliveries. Although women are required to pay only the remaining 20%,
      i.e., 900F CFA (1.4 Euros), some qualitative evidence suggests they actually pay
      more. The aim of this study is to test and then (if confirmed) to understand the
      hypothesis that the amounts paid by women are more than the official fee, i.e.,
      their 20% portion. A mixed method sequential explanatory design giving equal
      priority to both quantitative (n=883) and qualitative (n=50) methods was used in
      a rural health district of Ouargaye. Half (50%, median) of the women reported
      paying more than the official fee for a delivery. Health workers questioned the
      methodology of the study and the veracity of the women's reports. The three most
      plausible explanations for this payment disparity are: (i) the payments were for
      products used that were not part of the delivery kit covered by the official fee;
      (ii) the implementers had difficulty in understanding the policy; and (iii) there
      was improper conduct on the part of some health workers. Institutional design and
      organizational practices, as well as weak rule enforcement and organizational
      capacity, need to be considered more carefully to avoid an implementation gap in
      this public policy.

PMID- 23123309
TI  - Comparative genomics and evolutionary diversification of the duplicated fabp6a
      and fabp6b genes in medaka and three-spined stickleback.
AB  - We describe the evolutionary diversification of the duplicated ileal fatty acid
      binding protein genes (fabp6a and fabp6b) from Japanese ricefish (Oryzias
      latipes; medaka) and three-spined stickleback (Gasterosteus aculeatus). The
      fabp6a and fabp6b genes from medaka and three-spined stickleback encode
      polypeptides of 125-127 amino acids, which share highest sequence identity with
      their orthologs in teleost fishes and tetrapods. All Fabp6a and Fabp6b from
      different species cluster together in a distinct clade in phylogenetic analysis
      and the topology of the tree suggests that fabp6a and fabp6b from medaka and
      three-spined stickleback are most likely duplicated genes of an ancestral FABP6
      owing to teleost-specific whole-genome duplication. However, the topology of an
      alternate phylogenetic tree revealed that the duplication of the ancestral FABP6
      that gave rise to the extant fabp6a and fabp6b possibly occurred before the
      divergence of tetrapods and fishes. Conserved gene synteny was evident between
      the teleost fabp6a and fabp6b genes and the human FABP6 gene. The tissue-specific
      distribution of fabp6a transcripts suggests the retention of ancestral
      function(s) of the fabp6a gene in medaka and three-spined stickleback with
      acquisition of new function(s) in different tissues. However, the tissue-specific
      regulation of the fabp6b gene has diverged markedly in medaka and three-spined
      stickleback since the duplication of the fabp6 gene.

PMID- 23123310
TI  - Metabolomic study of plasma from female mink (Neovison vison) with low and high
      residual feed intake during restrictive and ad libitum feeding.
AB  - Metabolite profiling may elucidate changes in metabolic pathways under various
      physiological or nutritional conditions. In the present study two groups of
      female mink characterised as having a high (16 mink) or low (14 mink) residual
      feed intake were investigated during restrictive and ad libitum feeding. Blood
      samples were collected three times during the experimental period; during
      restrictive feeding, and four days and three weeks after the change to ad libitum
      feeding. Plasma samples were subjected to liquid chromatography mass spectrometry
      non-targeted metabolomics. Subjecting data to principal component analysis showed
      that there was no grouping of the data according to the residual feed intake. In
      contrast, data were clearly grouped according to feeding level. Identification of
      the metabolites responsible for this grouping showed that the plasma level of
      metabolites related to mobilisation of energy was high during restrictive
      feeding, e.g. betaine, carnitine, and creatine. During ad libitum feeding the
      plasma level of metabolites that can be characterised as biomarkers of meat
      intake (creatinine, carnosine, 1- and 3 methylhistidine) was high. The plasma
      level of lysophosphatidylcholine species was highest after four days of ad
      libitum feeding suggesting a short term imbalance in the transport or metabolism
      of these metabolites when changing the feeding level.

PMID- 23123312
TI  - Assessing the containment efficiency of a microbiological safety cabinet during
      the simultaneous generation of a nanoaerosol and a tracer gas.
AB  - The intention of this article is to compare the containment performance of a Type
      II microbiological safety cabinet (MSC) confronted with the simultaneous
      generation of a saline nanoparticle aerosol and a tracer gas (SF(6)). The back
      dissemination coefficient, defined as the ratio of the pollutant concentration
      measured outside the enclosure to the pollutant flow rate emitted inside the
      enclosure, is calculated in order to quantify the level of protection of each
      airborne contaminant tested for three enclosure operating configurations: an
      initial configuration (without perturbations), a configuration exposing a dummy
      in front of the enclosure (simulation of an operator), and a configuration
      employing the movement of a plate in front of the enclosure (simulation of human
      movement). Based on the results of this study, we observed that nanoparticulate
      and gaseous behaviours are strongly correlated, thus showing the predominance of
      air-driven transport over particle-specific behaviour. The average level of
      protection afforded by the MSC was found systematically slightly higher for the
      nanoaerosol than for the gas in the studied configurations (emission properties
      of the source, operating conditions, and measurement protocols). This improved
      protection efficiency, however, cannot be considered as a warrant of protection
      for operators since operating condition and ventilation parameters are still more
      influential on the containment than the pollutant nature (i.e. nanoaerosol or
      gas).

PMID- 23123313
TI  - Biological applications of peptides nanotubes: an overview.
AB  - Recently, self-assemblies of peptide nanotubes (PNTs) have appeared as one of the
      most interesting nanostructures to be explored in the field of nanotechnology.
      These smart assemblies can have diverse applications, such as in the design of
      nanoreactors, sensors, electronics, and stimulus-responsive materials. Recent
      publications indicate that PNT synthesis and production are under extensive
      study. However, a more detailed safety and nanotoxicology evaluation of these
      materials is still necessary. This is of paramount importance since interesting
      and novel biomedical applications based on the use of PNTs, including the
      development of smart nanodevices and drug delivery systems, are under way. To
      this end, the aim of this mini-review is to discuss the recent biomedical
      applications of PNTs and, it hopes, to be a source of inspiration for researchers
      in different areas of expertise related to nanotechnology.

PMID- 23123306
TI  - Myxobacterial tools for social interactions.
AB  - Myxobacteria exhibit complex social traits during which large populations of
      cells coordinate their behaviors. An iconic example is their response to
      starvation: thousands of cells move by gliding motility to build a fruiting body
      in which vegetative cells differentiate into spores. Here we review mechanisms
      that the model species Myxococcus xanthus uses for cell-cell interactions, with a
      focus on developmental signaling and social gliding motility. We also discuss a
      newly discovered cell-cell interaction whereby myxobacteria exchange their outer
      membrane (OM) proteins and lipids. The mechanism of OM transfer requires physical
      contact between aligned cells on a hard surface and is apparently mediated by OM
      fusion. The TraA and TraB proteins are required in both donor and recipient cells
      for transfer, suggesting bidirectional exchange, and TraA is thought to serve as
      a cell surface adhesin. OM exchange results in phenotypic changes that can alter
      gliding motility and development and is proposed to represent a novel microbial
      interacting platform to coordinate multicellular activities.

PMID- 23123314
TI  - Analogs of pancreatic polypeptide and peptide YY with a locked PP-fold structure
      are biologically active.
AB  - Pancreatic polypeptide (PP), peptide YY (PYY) and neuropeptide Y (NPY), members
      of the PP-fold family share a high degree of sequence homology. Nuclear magnetic
      resonance (NMR) and X-ray crystallography studies have shown these peptides can
      adopt a tightly organized tertiary structure called the PP-fold, which has long
      been assumed to be the active structure of this family of peptides. To date,
      however, no studies have been completed with PYY and PP which confirm if the PP
      fold structure is important for their physiological actions. The aim of the study
      was to test if PYY and PP locked into the PP-fold maintained biological activity.
      Therefore, we designed and produced analogs of PP and PYY in a cyclic
      conformation with two cysteine amino acid substitutions at the N-terminus and at
      position 27. These were oxidized to form a cysteine disulfide bond locking the
      peptides into the PP-fold structure. Studies demonstrate that the cyclic analogs
      have both similar in vivo activity to their parent molecules, and affinity for
      the Y2 and Y4 receptors. Results suggest that the proposed PP and PYY-fold is
      likely to be their biologically active conformation.

PMID- 23123315
TI  - Molecular phylogeny and host use evolution of the genus Exorista Meigen (Diptera:
      Tachinidae).
AB  - Members of the genus Exorista are parasitoids of a diverse array of insect hosts
      in the orders, Lepidoptera, Hymenoptera, Mantodea and Orthoptera. Phylogenetic
      relationships among subgenera and species of Exorista were inferred using four
      nuclear (Tpi, white, 18S and 28S) and four mitochondrial DNA (16S, 12S, ND5 and
      CO1) genes in maximum parsimony (MP), maximum likelihood (ML) and Bayesian Markov
      chain Monte Carlo (MCMC) analyses. Separate trees based on different sets of
      genes (mt DNA, nuclear, ribosomal, etc.) were compared and found to be nearly
      concordant. According to the molecular tree generated from the concatenated
      sequence data, the genus Exorista is paraphyletic. The phylogenetic analyses
      indicate the existence of two major clades of Exorista, including two genera
      Parasetigena and Phorocera. Morphological traits supporting clades indicated by
      molecular analyses within this genus are evaluated. Evolutionary patterns of the
      host use and host shifts are examined by optimizing host information using
      maximum likelihood on the molecular phylogeny. The ancestral host group of the
      tribe Exoristini (excluding Ctenophorinia and Phorinia) appears to be the order
      Lepidoptera, although hosts of some species are unknown. A major host shift to
      the Hymenoptera occurred in the clade of subgenus Adenia, and the ancestral state
      of subgenus Spixomyia is equivocal because there is little information available
      on the hosts in members of a subclade of this group (subclade A: Exorista
      hyalipennis group).

PMID- 23123317
TI  - Molecular methods for genotyping complex copy number polymorphisms.
AB  - Genome structural variation shows remarkable complexity with respect to copy
      number, sequence content and distribution. While the discovery of copy number
      polymorphisms (CNP) has increased exponentially in recent years, the transition
      from discovery to genotyping has proved challenging, particularly for CNPs
      embedded in complex regions of the genome. CNPs that are collectively common in
      the population and possess a dynamic range of copy numbers have proved the most
      difficult to genotype in association studies. This is in some part due to
      technical limitations of genotyping assays and the sequence properties of the
      genomic region being analyzed. Here we describe in detail the basis of a number
      of molecular techniques used to genotype complex CNPs, compare and contrast these
      approaches for determination of multi-allelic copy number, and discuss the
      potential application of these techniques in genetic studies. 

PMID- 23123316
TI  - The effects of nociceptin peptide (N/OFQ)-receptor (NOP) system activation in the
      airways.
AB  - The heptadecapeptide nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand for
      the N/OFQ peptide (NOP) receptor. It is cleaved from a larger precursor
      identified as prepronociceptin (ppN/OFQ). NOP is a member of the seven
      transmembrane-spanning G-protein coupled receptor (GPCR) family. ppN/OFQ and NOP
      receptors are widely distributed in different human tissues. Asthma is a complex
      heterogeneous disease characterized by variable airflow obstruction, bronchial
      hyper-responsiveness and chronic airway inflammation. Limited therapeutic
      effectiveness of currently available asthma therapies warrants identification of
      new drug compounds. Evidence from animal studies suggests that N/OFQ modulates
      airway contraction and inflammation. Interestingly up regulation of the N/OFQ-NOP
      system reduces airway hyper-responsiveness. In contrast, inflammatory cells
      central to the inflammatory response in asthma may be both sources of N/OFQ and
      respond to NOP activation. Hence paradoxical dysregulation of the N/OFQ-NOP
      system may potentially play an important role in regulating airway inflammation
      and airway tone. To date there is no data on N/OFQ-NOP expression in the human
      airways. Therefore, the potential role of N/OFQ-NOP system in asthma is unknown.
      This review focuses on its physiological effects within airways and potential
      value as a novel asthma therapy.

PMID- 23123318
TI  - A simple iterative method to optimize protein-ligand-binding residue prediction.
AB  - This article describes an iterative method (IM) for improving protein-ligand
      binding residue prediction. Through modifying the binding residue definition in
      every iteration, this method, step by step, increased the performance of the
      classifiers used. Using a balanced assessment index (BAI), the classifier
      optimized by the IM achieved a value of 80.4 that is bigger than the one (66.9)
      of the initial classifier. According to mean per-instance BAI scores, a direct
      comparison of methods has been carried out along with an analysis of statistical
      significance of the differences in performance. The results show that the
      iterative method (IM) does achieve a higher mean score than the threshold
      altering method (TAM) used in our previous study and there is a statistically
      significant difference between the two methods. The IM has a significant
      advantage that it is independent of the concrete residue characterization models
      and learning algorithms, and more extensively applicable. These results indicate
      that optimizing the binding residue definition is also an effective approach to
      improve protein-ligand-binding residue prediction.

PMID- 23123319
TI  - MYH9-related disease: five novel mutations expanding the spectrum of causative
      mutations and confirming genotype/phenotype correlations.
AB  - MYH9-related disease (MYH9-RD) is a rare autosomal dominant syndromic disorder
      caused by mutations in MYH9, the gene encoding for the heavy chain of non-muscle
      myosin IIA (myosin-9). MYH9-RD is characterized by congenital
      macrothrombocytopenia and typical inclusion bodies in neutrophils associated with
      a variable risk of developing sensorineural deafness, presenile cataract, and/or
      progressive nephropathy. The spectrum of mutations responsible for MYH9-RD is
      limited. We report five families, each with a novel MYH9 mutation. Two mutations,
      p.Val34Gly and p.Arg702Ser, affect the motor domain of myosin-9, whereas the
      other three, p.Met847_Glu853dup, p.Lys1048_Glu1054del, and p.Asp1447Tyr, hit the
      coiled-coil tail domain of the protein. The motor domain mutations were
      associated with more severe clinical phenotypes than those in the tail domain.

PMID- 23123321
TI  - 17q21.31 microdeletion associated with infantile spasms.
AB  - Patients with 17q21.31 microdeletions frequently have neurologic abnormalities,
      especially seizures. This report is of a child with a deletion in this location
      who developed infantile spasms, a seizure type not specifically described in this
      syndrome. FISH analysis of parental blood metaphases demonstrated that the
      deletions occurred de novo. The deleted region encompasses the previously defined
      critical region for the 17q21.31 microdeletion syndrome, and includes the gene
      encoding for corticotropin-releasing hormone receptor 1, a protein implicated in
      hyperexcitability, and potentially in infantile spasms. Treatment with ACTH led
      to spasm cessation, consistent with its expected repression of CRH levels, which
      should be augmented by CRHR1 deletion, although this response was transient.

PMID- 23123322
TI  - Termination of calcium-induced calcium release by induction decay: an emergent
      property of stochastic channel gating and molecular scale architecture.
AB  - Calcium-induced calcium release (CICR) is an inherently regenerative process due
      to the Ca(2+)-dependent gating of ryanodine receptors (RyRs) in the
      sarco/endoplasmic reticulum (SR) and is critical for cardiac excitation
      contraction coupling. This process is seen as Ca(2+) sparks, which reflect the
      concerted gating of groups of RyRs in the dyad, a specialised junctional
      signalling domain between the SR and surface membrane. However, the mechanism(s)
      responsible for the termination of regenerative CICR during the evolution of
      Ca(2+) sparks remain uncertain. Rat cardiac RyR gating was recorded at
      physiological Ca(2+), Mg(2+) and ATP levels and incorporated into a 3D model of
      the cardiac dyad which reproduced the time-course of Ca(2+) sparks, Ca(2+) blinks
      and Ca(2+) spark restitution. Model CICR termination was robust, relatively
      insensitive to the number of dyadic RyRs and automatic. This emergent behaviour
      arose from the rapid development and dissolution of nanoscopic Ca(2+) gradients
      within the dyad. These simulations show that CICR does not require intrinsic
      inactivation or SR calcium sensing mechanisms for stability and cessation of
      regeneration that arises from local control at the molecular scale via a process
      we call 'induction decay'.

PMID- 23123320
TI  - Homozygous stop mutation in the SNX10 gene in a consanguineous Iraqi boy with
      osteopetrosis and corpus callosum hypoplasia.
AB  - Recently a mutation in the SNX10 gene that belongs to the sorting nexin family
      was identified as a cause of a new subset of human autosomal recessive
      osteopetrosis. Here, we identified a novel homozygous mutation (c.46C > T,
      p.Arg16X) in SNX10, in an Iraqi boy from a consanguineous family with a history
      of infantile osteopetrosis. The proband exhibited macrocephaly, prominent
      forehead, proptosis of the eyes, strabismus, splenomegaly and joint hyperlaxity.
      Bone X-rays showed increased bone density, metaphyseal under-modelling,
      transverse alternating bands of greater and lesser density in tubular bones,
      anteriorly notched vertebral bodies and bone-in-bone appearance. Brain atrophy,
      external hydrocephalus and thin corpus callosum were noted at the brain MRI and
      CT scan. Blood test results revealed the presence of anaemia and leukopenia. Our
      findings confirm the role of SNX10 in autosomal recessive osteopetrosis and help
      to better define the core set of manifestations associated with this new
      pathological entity.

PMID- 23123324
TI  - [Advances in reconstructive options of nerve injuries in the hand].
AB  - The author summarizes the most important data about the development of
      reconstructive techniques of nerve injuries in the hand based on literature
      references and the author's own experience in the past decades. A new bulk of
      knowledge turned into a common property related to the micro- and macroanatomic
      structure of peripheral nerves, the process of nerve regeneration, and the
      technical conditions of nerve reconstructive operations. This knowledge is a
      prerequisite for hand surgeons to perform their nerve reconstructive operations
      on a contemporary high level with an optimal result. After a critical review of
      literature data, the author reports his own experience and sketches the coming
      possible roads. A detailed list of references is also provided for those who are
      interested in the field.

PMID- 23123325
TI  - [Stomatologic complications of eating disorders].
AB  - Since the 1990s numerous international experts have reported about the somatic
      complications of eating disorders including those having a dental and
      stomatological nature. Several reports emphasised that deformations in the oral
      cavity resulting from this grave nutritional disease typical of the young
      generation could already appear in the early stage and, therefore, dentists are
      among the first to diagnose them. Dentists are still often unaware of the
      importance of their role in multidisciplinary treatment. Even if they knew what
      the disease was about and recognised it on the basis of deformations in the oral
      cavity in time, their advice that their patients should brush their teeth more
      often would fail to eliminate the root cause of the problem. Not only the
      earliest possible treatment of the complications of the bingeing-purging
      mechanism and the maintenance of oral hygiene are important, but controlling and
      curing pathological habits with active participation of psychiatrists are also
      required to ensure full recovery. Due to the multidisciplinary nature of the
      disease, manifold communication is required. For this reason, publishing the
      dental ramifications of organic and systemic diseases at dental conferences and
      in technical journals, as well as providing information about oral complications
      of eating disorders for general practitioners and specialists are particularly
      important.

PMID- 23123326
TI  - [Effect of a new dietary supplement on sperm quality].
AB  - INTRODUCTION: There is a decline in male fertility thus new treatments are
      needed. AIMS: To test the efficacy of a new dietary supplement developed in the
      USA and registered as a drug of cure in Hungary (OGYI). METHODS: In a clinical
      trial 100 men with low sperm quality (spermium count 5-20 M/ml, good motility 10
      40%, and adverse shape 30-50%) were examined. RESULTS: Sperm parameters were
      measured before and after a 3-month treatment and after another 3-month without
      treatment. This dietary supplement statistically and clinically significantly
      improved sperm count and motility. In 74 cases this dietary supplement
      demonstrated a beneficial effect on sperm quality (more than 10% increase in
      sperm count, or quality of motility, or shape); in 16 cases the improvement
      exceeded 30%. No adverse effect could be accounted for this treatment.
      CONCLUSIONS: This new dietary supplement may contribute to the treatment of male
      infertility.

PMID- 23123323
TI  - Mitochondrial dysfunction causing cardiac sodium channel downregulation in
      cardiomyopathy.
AB  - Cardiomyopathy is associated with cardiac Na(+) channel downregulation that may
      contribute to arrhythmias. Previously, we have shown that elevated intracellular
      NADH causes a decrease in cardiac Na(+) current (I(Na)) signaled by an increase
      in mitochondrial reactive oxygen species (ROS). In this study, we tested whether
      the NADH-mitochondria ROS pathway was involved in the reduction of I(Na) in a
      nonischemic cardiomyopathic model and correlated the findings with myopathic
      human hearts. Nonischemic cardiomyopathy was induced in C57BL/6 mice by
      hypertension after unilateral nephrectomy, deoxycorticosterone acetate (DOCA)
      pellet implantation, and salt water substitution. Sham operated mice were used as
      controls. After six weeks, heart tissue and ventricular myocytes isolated from
      mice were utilized for whole cell patch clamp recording, NADH/NAD(+) level
      measurements, and mitochondrial ROS monitoring with confocal microscopy. Human
      explanted hearts were studied using optical mapping. Compared to the sham mice,
      the arterial blood pressure was higher, the left ventricular volume was
      significantly enlarged (104.7+/-3.9 vs. 87.9+/-6.1 MUL, P<0.05), and the ejection
      fraction was reduced (37.1+/-1.8% vs. 49.4+/-3.7%, P<0.05) in DOCA mice. Both the
      whole cell and cytosolic NADH level were increased (279+/-70% and 123+/-2% of
      sham, respectively, P<0.01), I(Na) was decreased (60+/-10% of sham, P<0.01), and
      mitochondrial ROS overproduction was observed (2.9+/-0.3-fold of sham, P<0.01) in
      heart tissue and myocytes of myopathic mice vs. sham. Treatment of myocytes with
      NAD(+) (500 MUM), mitoTEMPO (10 MUM), chelerythrine (50 MUM), or forskolin (5
      MUM) restored I(Na) back to the level of sham. Injection of NAD(+) (100mg/kg) or
      mitoTEMPO (0.7 mg/kg) twice (at 24h and 1h before myocyte isolation) to animals
      also restored I(Na). All treatments simultaneously reduced mitochondrial ROS
      levels to that of controls. CD38 was found to transduce the extracellular NAD(+)
      signal. Correlating with the mouse model, failing human hearts showed a reduction
      in conduction velocity that improved with NAD(+). Nonischemic cardiomyopathy was
      associated with elevated NADH level, PKC activation, mitochondrial ROS
      overproduction, and a concomitant decrease in I(Na). Reducing mitochondrial ROS
      by application of NAD(+), mitoTEMPO, PKC inhibitors, or PKA activators, restored
      I(Na). NAD(+) improved conduction velocity in human myopathic hearts.

PMID- 23123327
TI  - [Comparison of functional and morphological changes of transplanted kidneys from
      marginal and ideal donors].
AB  - INTRODUCTION: Despite an increased number of cadaver donors and organ
      transplantations, there is a marked increase in the number of patients included
      in the transplantation waiting list. AIM AND METHOD: The aim of the study was to
      evaluate functional and morphologic changes of kidney allografts obtained from
      marginal (n = 63) and "ideal" donors (n = 186). In patients with kidneys from
      marginal donors, the impact of donor age and the presence of hypertension in
      donors on kidney function were also studied. RESULTS: One year after kidney
      transplantation, kidney function was similar in patients transplanted with
      kidneys from marginal and "ideal" donors, although significant morphologic
      differences were observed between the two groups. However, five years after
      transplantation serum creatinine (p = 0.0001) and eGFR (p = 0.003) were
      significantly different between patients transplanted with kidneys from marginal
      and "ideal" donors. There was also a significant difference in serum creatinine
      level of patients who received kidneys from donors older than 55 years of age
      compared to patients whose kidney allografts were obtained form donor who has
      hypertension (p = 0.0003). Acute rejection episodes (p = 0.0004) and interstitial
      fibrosis/tubular atrophy (p = 0.002) occurred more frequently in patients with
      kidneys from marginal compared to those from "ideal" donors. CONCLUSION: One year
      after kidney transplantation renal function is similar in patients transplanted
      with kidneys from marginal and "ideal" donors, but patients with kidneys from
      marginal donors have significantly more impaired renal function five years after
      kidney transplantation.

PMID- 23123328
TI  - [Simultaneous presentation of Brugada syndrome and primary aldosteronism].
AB  - The authors present a case of a 42-year-old male patient, who was referred for
      evaluation for tachycardia. Detailed studies revealed Brugada syndrome and
      hypokalaemia due to primary aldosteronism. With this case report the authors draw
      attention to the risk of malignant ventricular tachycardia in a patient with low
      potassium level, especially in case of coexisting Brugada syndrome.

PMID- 23123330
TI  - Respiratory motion models: a review.
AB  - The problem of respiratory motion has proved a serious obstacle in developing
      techniques to acquire images or guide interventions in abdominal and thoracic
      organs. Motion models offer a possible solution to these problems, and as a
      result the field of respiratory motion modelling has become an active one over
      the past 15 years. A motion model can be defined as a process that takes some
      surrogate data as input and produces a motion estimate as output. Many techniques
      have been proposed in the literature, differing in the data used to form the
      models, the type of model employed, how this model is computed, the type of
      surrogate data used as input to the model in order to make motion estimates and
      what form this output should take. In addition, a wide range of different
      application areas have been proposed. In this paper we summarise the state of the
      art in this important field and in the process highlight the key papers that have
      driven its advance. The intention is that this will serve as a timely review and
      comparison of the different techniques proposed to date and as a basis to inform
      future research in this area.

PMID- 23123331
TI  - Seventy-two-hour release formulation of the poorly soluble drug silybin based on
      porous silica nanoparticles: in vitro release kinetics and in vitro/in vivo
      correlations in beagle dogs.
AB  - The objective of this study was to prepare a 72 h-release formulation of silybin
      (72 h-SLB) using a combination of solid dispersion, gel matrix and porous silica
      nanoparticles (PSNs) and to investigate the in vitro/in vivo correlations
      (IVIVCs). The results of scanning electron microscopy and N(2) adsorption
      demonstrated that empty PSNs possessed a spherical shape, a highly porous
      structure, a large specific surface area (385.89 +/- 1.12 m(2)/g) and a small
      pore size (2.74 nm on average). The in vitro dissolution profiles of both 72 h
      SLB and silybin-loaded PSNs in different concentrations (0.01, 0.06 and 0.08M) of
      Na(2)CO(3) solutions revealed that 0.06 M Na(2)CO(3) solution was the optimal
      medium in which silybin could be released from 72 h-SLB with first-order release
      kinetics and from PSNs with Higuchi kinetics. Furthermore, the IVIVCs of 72 h-SLB
      and silybin-loaded PSNs in beagle dogs were also established. Using 0.06 M
      Na(2)CO(3) solution as the in vitro dissolution medium, a good linear
      relationship could be achieved for both 72 h-SLB and silybin-loaded PSNs. The
      findings support the fact that the 72 h-SLB (consisting of solid dispersion,
      regular gel matrix and PSNs) together with Na(2)CO(3) solution as an in vitro
      dissolution medium can be developed into a promising formulation for poorly
      soluble drugs, which enjoys a good IVIVC.

PMID- 23123332
TI  - Zymomonas mobilis culture protects against sepsis by modulating the inflammatory
      response, alleviating bacterial burden and suppressing splenocyte apoptosis.
AB  - Microorganisms with immunomodulating effects beneficially affect the host
      organism by improving the microbial equilibrium and balancing the immune system.
      Zymomonas mobilis is reported to have antagonistic properties against yeast and
      other pathogenic microorganisms in humans and animals. This study assessed the
      effects of Z. mobilis UFPEDA 202 (10(9)CFU/mL) cultures on polymicrobial sepsis
      induced by cecal ligation and puncture (CLP). The survival of animals subjected
      to lethal sepsis was evaluated after pre-treatment, post-treatment or a
      combination of both. 6h after the induction of sepsis, neutrophil migration, the
      number of bacteria, myeloperoxidase, TNF-alpha, MCP-1, and IL-10 were performed
      in the peritoneal lavage of animals. Histopathological changes in the spleen of
      animals were evaluated by light microscopy, and apoptosis of splenocytes was
      analyzed by transmission electron microscopy. The results showed that the
      combination of prophylactic and therapeutic treatment with Z. mobilis increased
      the survival of animals by 50% at 96 h after the induction of sepsis. There was a
      reduction in the levels of TNF-alpha and myeloperoxidase (MPO) in lung tissue.
      There was also a reduction in the number of viable bacteria in peritoneal fluid.
      However, increases in neutrophil migration and IL-10 levels were observed. The
      observed levels of MCP-1 remained similar to the control. Histopathology analysis
      showed a decrease in acute lung injury. The group pre-treated with the Z. mobilis
      culture demonstrated a marked decrease in the number of apoptotic cells in the
      spleen (24%). This study demonstrates that Z. mobilis cultures increased the
      survival of animals with severe sepsis. This survival was mediated by improvement
      of neutrophil migration, enhanced activity against pathogenic enteric bacteria
      and reduced lung injury.

PMID- 23123333
TI  - Determining soil remedial action criteria for acute effects: the challenge of
      copper.
AB  - Gastrointestinal (GI) symptoms, the primary acute effect of the essential
      micronutrient copper, paradoxically occur at lower exposure levels than
      hepatotoxicity, the primary chronic effect. We developed a remedial action
      criterion (RAC) for copper to protect against GI symptoms, which primarily relate
      to the stomach copper concentration, and subside within an hour. Using Monte
      Carlo methods, we generated a distribution of RACs protective against GI symptoms
      for a 1 h exposure (hourly RACs) based on soil ingestion rate, volume of liquid
      and food in the stomach, and bioaccessibility. We then generated a distribution
      of daily RACs, selected as the minimum hourly RAC for each day over a year,
      constrained by total daily soil ingestion. Next, we identified a percentile of
      the distribution of daily RACs, and associated RAC, that would result in a high
      probability of having a minimal number of GI symptom episodes per year. Our
      analysis indicates that a copper concentration of 3600 mg/kg would result in a
      95% probability of having fewer than five episodes of GI symptoms per year, for a
      child ingesting outdoor soil 180 days per year. Children residing near copper
      smelters are most likely to experience GI symptoms from ingestion of copper in
      soil.

PMID- 23123334
TI  - Diastereomerically pure platinum(II) complexes as antitumoral agents.: The
      influence of the mode of binding {(N), (N,O)- or (C,N)}- of (1S,2R)[(eta5
      C5H5)Fe{(eta5-C5H4)CHNCH(Me)CH(OH)C6H5}] and the arrangement of the auxiliary
      ligands.
AB  - The study of the reactivity of (1S,2R) [(eta(5)-C(5)H(5))Fe{[(eta(5)-C(5)H(4))
      CHNCH(Me)CH(OH)C(6)H(5)}] (1a) with cis-[PtCl(2)(DMSO)(2)] under different
      experimental conditions has allowed to isolate and characterize three pairs of
      isomeric and diastereomerically pure platinum(II) complexes. Two of the pairs are
      the trans- and cis- isomers of (1S,2R)[Pt{(eta(5)-C(5)H(5))Fe[(eta(5)
      C(5)H(4))CHNCH(Me)CH(OH)C(6)H(5)]}Cl(2)(DMSO)] [trans-(2a) and cis-(3a),
      respectively], and of (1S,2R) [Pt{(kappa(2)-N,O)(eta(5)-C(5)H(5))Fe[(eta(5)
      C(5)H(4))CHNCH(Me)CH(O)C(6)H(5)]}Cl(DMSO)], {trans-(Cl, N) in (4a)} or a cis-(Cl,
      N) {in (5a)}; while the third one is formed by platinacycles: [Pt{(kappa(2)
      C,N[(eta(5)-C(5)H(3))]CHN-CH(Me)CH(OH)C(6)H(5)]Fe(eta(5)-C(5)H(5))}Cl(DMSO)] with
      different planar chirality [S(p) (in 6a) or R(p) (in 7a)]. The crystal structures
      of compounds 2a, 3a, 5a and 6a are also reported. The cytotoxic assessment of 1a
      7a on lung (A549), breast (MDA-MB-231) and colon (HCT-116) cancer cell lines is
      also reported and reveals that the potency of the complexes is strongly dependent
      on the mode of binding of the iminoalcohol {(N) in 2a and 3a, (N,O)(-) in 4a and
      5a or (C,N)(-) in 6a and 7a}, the relative arrangement of the monodentate ligands
      (in 2a-5a), and the planar chirality of the 1,2-ferrocenylunit in (6a and 7a).
      Among the new products (2a-7a), compounds 4a and 5a exhibit the highest potency
      with IC(50) values smaller than cisplatin in the three cancer cell lines assayed.
      Electrophoretic DNA migration studies in the presence of 2a-7a have been
      performed in order to get further insights into their mechanism of action. A
      comparative study of the solution behaviour of all the complexes in DMSO-d(6) or
      in DMSO-d(6):D(2)O (1:1) mixtures at 298 K is also reported.

PMID- 23123335
TI  - Features and full reversibility of the renal toxicity of the ruthenium-based drug
      NAMI-A in mice.
AB  - The ruthenium-based compound imidazolium trans-imidazoledimethylsulfoxide
      tetrachlororuthenate (NAMI-A) is free of cytotoxicity up to 1mM concentration
      after 1h in vitro exposure of the LLC-PK1 renal tubule cells. In vivo, one cycle
      of i.p. administrations of 35 mg/kg/day NAMI-A (1 cycle=6 consecutive days), is
      free of a measurable toxicity on mouse kidneys. After two cycles with a one-week
      drug-free washout between cycles, mitochondrial membrane potential of the renal
      cells drops by 37% (p<0.05), serum creatinine increases by 30% (p<0.05) and a
      significant decrease of body weight of 12% (p<0.05) occurs. These parameters
      return to normal within 7 days after the end of treatment. A cycle-dependent
      alteration of glomeruli and a diffused swelling of renal tubules are also evident
      leading to a significant alteration of these structures after the third cycle.
      These effects are completely prevented if a 2-week drug free washout is used
      between two consecutive cycles. These data support the toxic accumulation of NAMI
      A or of its products of transformation in the kidneys and stress the need of at
      least 14 days washout between two treatment cycles when the drug is given daily
      for 6 consecutive days.

PMID- 23123336
TI  - Factors that distort the heme structure in Heme-Nitric Oxide/OXygen-Binding (H
      NOX) protein domains. A theoretical study.
AB  - DFT and dispersion-corrected DFT calculations were carried out to probe the
      factors that distort the heme structure in Heme-Nitric oxide/OXygen-binding (H
      NOX) protein domains. Various model systems that include heme, heme+surrounding
      residues, and heme+surrounding residues+additional protein environment were
      examined; the latter system was calculated with a quantum mechanics/molecular
      mechanics (QM/MM) method. The computations were extended to a myoglobin (Mb)
      protein, in which the heme structure is quite planar, in contrast to that in H
      NOX. The natural tendency of the heme is to be planar. The strong structural
      distortion in H-NOX is mainly brought about by the intermolecular interactions
      between the whole heme molecule (heme ring plus its peripheral substituents) and
      the surrounding residues, among which the polar residues (Tyr140, Pro115, Mse98)
      play major roles in distorting the heme structure. The two peripheral propionate
      substituents that are oriented on the same side of the heme plane can also make
      the molecule distort, but the distortion caused by this factor is not
      significant. In Mb, the surrounding residues considered are all nonpolar and do
      not cause a structural distortion. The different structural features of the heme
      macrocycle in the different proteins (H-NOX and Mb) are reproduced by the
      calculations. The dispersion correction is necessary, since it improves the
      calculated structures. The effects of the distortion on the binding affinity of
      the axial ligand to the heme were also examined.

PMID- 23123337
TI  - Synthesis and application of intercellular Ca2+-sensitive fluorescent probe based
      on quantum dots.
AB  - A novel Ca(2+)-sensitive fluorescent probe was synthesized and characterized with
      a coupled method that coupled di[2-(N,N-dicarboxylmethyl)amino]ethyl ether (EGTA)
      to the surface of mercaptoethylamine-modified CdTe quantum dots (CdTe/MA-EGTA
      QDs). The application of this probe to detect intercellular Ca(2+) change in the
      leaf cells of Arabidopsis thaliana was studied. Results from transmission
      electron micrographs showed that the particle size of CdTe/MA-EGTA was about 3-4
      nm; the fluorescent spectrum indicated that the excitation spectral ranged from
      350 to 490 nm with a narrow and symmetric emission spectral peak at 565 nm when
      excited by 400 nm, and capillary electrophoresis demonstrated that CdTe/MA-EGTA
      was obtained by a coupling reaction. When the detected conditions were set as an
      excitation wavelength of 514 nm and detection wavelength of 561-604 nm, the
      increase of Ca(2+) in A. thaliana leaf cells and the rapidly quenching effect of
      fluorescence signal induced by exogenous treatment of jasmonate acid (JA) could
      be measured using laser scanning confocal microscopy. The quenching rate of
      traditional Ca(2+)-sensitive fluorescent probe Fluo-3 reached about 80% within a
      minute when exciting at 488 nm, which was much faster than the novel fluorescent
      probe CdTe/MA-EGTA. CdTe/MA-EGTA, however, was better at resisting photo
      bleaching and was more suitable for long-term tracking and monitoring than Fluo
      3.

PMID- 23123338
TI  - Synthesis, characterization, DNA binding properties and antioxidant activity of a
      manganese(II) complex with NO6 chromophore.
AB  - The mononuclear complex [Mn(thiophenyl-2-carboxylate)(2)(H(3)tea)] (1), where
      H(3)tea=triethanolamine has been synthesized, characterized, while the DNA
      binding properties and the antioxidant activity were studied. The crystal
      structure of 1 is also reported. The interaction between 1 and calf thymus double
      stranded (ds) DNA was electrochemically at a calf thymus DNA (CT-DNA) modified
      carbon paste electrode (CPE) and spectrophotometrically investigated,
      respectively. Adsorptive transfer stripping voltammetry showed that the
      interaction mode between 1 and CT-DNA depends on manganese(II) complex
      concentration. UV studies between 1 and CT-DNA revealed that 1 can bind to CT-DNA
      by the intercalative binding mode and the binding constant has been calculated. A
      competitive study with acridine orange (AO) showed that 1 exhibits the ability to
      displace the DNA-bound AO, since 1 binds to the DNA in competition with AO. In
      vitro antioxidant activity of free ligands and 1 was evaluated using five
      different antioxidant assays: a) interaction with 1, 1-diphenyl-2-picryl-hydrazyl
      (DPPH) stable free radical, b) the EtaOmicron mediated oxidation of DMSO, c)
      scavenging of superoxide anion radicals, d) inhibition of lipid peroxidation and
      e) soybean lipoxygenase (LOX) inhibition. The results revealed the selectivity of
      the manganese complex to different free radicals as a consequence of its
      physicochemical feature. In particular, 1 presents significant inhibitory
      activity on LOX, with IC(50)=30 MUM and selectivity to the inhibition of
      superoxide anion radicals and thus a promising candidate as a superoxide
      dismutase (SOD) biomimetic.

PMID- 23123339
TI  - Potent antibacterial activity of a novel silver nanoparticle-halloysite nanotube
      nanocomposite powder.
AB  - Halloysite nanotubes (HNTs), natural nanotube, have been developed as a support
      for loading of antibacterial agents. Firstly, HNTs were modified by silane
      coupling agent (KH-792). And then, modified HNTs were immersed in silver nitrate
      solution and a complex reaction between the two amino groups of KH-792 and silver
      ions formed, leading to large clusters on the surface of HNTs. Finally, these
      silver containing clusters were converted into silver nanoparticles (Ag NPs) with
      about 5nm diameter by reduction process. A new antibacterial agent, Ag NPs/HNTs,
      was characterized by X-ray fluorescence (XRF), X-ray diffraction (XRD), X-ray
      photoelectron spectroscopy (XPS), transmission electron microscopy (TEM) and
      scanning transmission electron microscopy-energy dispersive X-ray analysis (STEM
      EDX). The antibacterial test indicated that Ag NPs/HNTs showed good antibacterial
      performance against Gram-negative bacteria (Escherichia coli) and Gram-positive
      bacteria (Staphylococcus aureus).

PMID- 23123340
TI  - Accommodation of CO in the di-heme active site of cytochrome bd terminal oxidase
      from Escherichia coli.
AB  - Catalytic mechanisms of reduction of O(2) to 2H(2)O by respiratory terminal
      oxidases have been extensively investigated. Tri-heme (b(558), b(595), d)
      cytochrome bd oxidases presumably utilize a dihemic site composed of high-spin
      hemes d and b(595). We performed a CO photolysis/recombination study of the
      purified fully reduced cytochrome bd from Escherichia coli. Spectrum of CO
      photolysis suggests photodissociation of the ligand from heme d and from part of
      heme b(595). This is the first clear evidence of interaction of heme b(595) with
      CO at room temperature. The amount of the heme d-CO species is higher after
      recombination than before photolysis. In the enzyme population with heme b(595)
      bound to CO, heme d remains unliganded, hence the dihemic O(2)-reducing pocket in
      cytochrome bd can bind one rather than two diatomic molecules. Occupancy of the
      site by one ligand molecule probably blocks access of a second molecule. Thus
      cytochrome bd exhibits strong negative cooperativity in ligand binding.
      Immediately after photolysis/recombination CO occupies 100% of the heme d sites,
      whereas after equilibration, the ligand gets located at heme d in 90-95% and at
      heme b(595) in 5-10% of the cytochrome. The equilibration process is possibly
      associated with an exchange of heme d endogenous ligand.

PMID- 23123341
TI  - Conversion of natively unstructured alpha-synuclein to its alpha-helical
      conformation significantly attenuates production of reactive oxygen species.
AB  - The intracellular alpha-synuclein (alpha-syn) protein, whose conformational
      change and aggregation have been closely linked to the pathology of Parkingson's
      disease (PD), is highly populated at the presynaptic termini and remains there in
      the alpha-helical conformation. In this study, circular dichroism confirmed that
      natively unstructured alpha-syn in aqueous solution was transformed to its alpha
      helical conformation upon addition of trifluoroethanol (TFE). Electrochemical and
      UV-visible spectroscopic experiments reveal that both Cu (I) and Cu (II) are
      stabilized, with the former being stabilized by about two orders of magnitude.
      Compared to unstructured alpha-syn (Binolfi et al., J. Am. Chem. Soc. 133 (2011)
      194-196), alpha-helical alpha-syn stabilizes Cu (I) by more than three orders of
      magnitude. Through the measurements of H(2)O(2) and hydroxyl radicals (OH) in
      solutions containing different forms of Cu (II) (free and complexed by
      unstructured or alpha-helical alpha-syn), we demonstrate that the significantly
      enhanced Cu (I) binding affinity helps inhibit the production of highly toxic
      reactive oxygen species, especially the hydroxyl radicals. Our study provides
      strong evidence that, as a possible means to prevent neuronal cell damage,
      conversion of the natively unstructured alpha-syn to its alpha-helical
      conformation in vivo could significantly attenuate the copper-modulated ROS
      production.

PMID- 23123342
TI  - Ruthenium arene complexes as HIV-1 integrase strand transfer inhibitors.
AB  - The quinolone HL(1) and the hydroxypyrimidine-carboxamide HL(2) were designed and
      synthesized as models of the HIV integrase strand transfer inhibitors
      Elvitegravir and Raltegravir (brand name Isentress), with the aim to study their
      complexing behavior and their biological activity. The Ru(arene) complexes
      [RuCl(eta(6)-p-cym)L(1)], [RuCl(eta(6)-p-cym)L(2)] and
      [RuCl(hexamethylbenzene)L(2)] were also synthesized and spectroscopically
      characterized and their X-ray diffraction structures were discussed. The ligands
      and the complexes showed inhibition potency in the sub/low-micromolar
      concentration range in anti-HIV-1 integrase enzymatic assays, with selectivity
      toward strand transfer catalytic process, without any significant cytotoxicity on
      cancer cells.

PMID- 23123343
TI  - Multilayer material properties of aorta determined from nanoindentation tests.
AB  - In a wide range of biomechanical modeling of aorta from traumatic injury to stent
      grafts, the arterial wall has been considered as a single homogeneous layer
      vessel, ignoring the fact that arteries are composed of distinct anatomical
      layers with different mechanical characteristics. In this study, using a custom
      made nanoindentation technique, changes in the mechanical properties of porcine
      thoracic aorta wall in the radial direction were characterized using a quasi
      linear viscoelastic model. Two layers of equal thickness were mechanically
      distinguishable in descending aorta based on the radial variations in the
      instantaneous Young's modulus E and reduced relaxation function G(t). Overall,
      comparison of E and G(infinity) of the outer half (70.27+/-2.47 kPa and 0.35+/
      0.01) versus the inner half (60.32+/-1.65 kPa and 0.33+/-0.01) revealed that the
      outer half was stiffer and showed less relaxation. The results were used to
      explain local mechanisms of deformation, force transmission, tear propagation and
      failure in arteries.

PMID- 23123344
TI  - A simple immune complex dissociation ELISA for leishmaniasis: standardization of
      the assay in experimental models and preliminary results in canine and human
      samples.
AB  - Visceral leishmaniasis, caused by Leishmania (Leishmania) chagasi, is a chronic
      parasitic disease of humans and dogs. Confirmation of the protozoal agent in bone
      marrow, lymph node or spleen aspirate is diagnostic, while specific-IgG serology
      is used mainly for epidemiology despite the general presence of high levels of
      serum immunoglobulin. Anecdotal reports of false-negative serology in active
      disease cases are known and are ascribed to the formation of immune complexes.
      Because dissociation of immune complexes can be accomplished by acid treatment,
      we devised a simple, routine enzyme immunoassay (ELISA) for the dissociation of
      immune complexes in serum samples using acid treatment in wells adsorbed with
      Leishmania antigen (dELISA). Confirmatory acid dot-blot was also developed for
      antigen detection by anti-Leishmania rabbit antiserum. In experimental L. chagasi
      hamster models, immune complexes interfered with ELISA mostly in the 30 and 60
      days postinfection, according to both dELISA and antigen dot-blot results. In
      larger samples from endemic areas, dELISA was positive in 10% of seronegative dog
      samples (7/70) and 3.5% in negative human samples (3/88), showing that dELISA
      could be used in the serodiagnosis of visceral leishmaniasis. Moreover, dELISA
      could be used as an alternative approach to screening asymptomatic visceral
      leishmaniasis patients, instead of invasive confirmatory testing.

PMID- 23123345
TI  - A double-blind controlled field trial of doxycycline and albendazole in
      combination for the treatment of bancroftian filariasis in India.
AB  - In a placebo controlled field trial, the effects of doxycycline (200mg/day) for
      23 days followed by doxycycline (200mg/day) in combination with albendazole (ABZ)
      (400mg/day) for 7 days on depletion of Wolbachia endobacteria from Wuchereria
      bancrofti and microfilaricidal activity were studied in 68 patients (34 males and
      34 females) from West Bengal, India. The drugs in combination (i.e.,
      doxycycline+ABZ) provided the best efficacy by totally eliminating the
      circulating microfilaria (mf) (in 42% cases) on day 365 with (99.8%, P<0.05)
      suppression even on day 365 post-treatment compared to both exclusive doxycycline
      (69%, P<0.05) and ABZ (89%, P<0.05) groups. Thus, our results have established
      that a 30-day course of doxycycline in combination with a 7-day course of ABZ is
      sufficient to ensure long-term reduction in mf level by depleting Wolbachia from
      worm tissues. Doxycycline combined with ABZ led to a greater reduction in mf
      density in blood at 4 months (post-treatment) in comparison to doxycycline or ABZ
      alone. There were significant differences between the three treatments after 12
      months (post-treatment). Further, the impact of a 7-day regimen of ABZ was
      surprisingly good in reducing mf compared to doxycycline-alone group. Adverse
      reactions were mild. A 30-day course of doxycycline and ABZ in combination is a
      safe and well-tolerated treatment for lymphatic filariasis with significant
      activity against microfilaremia.

PMID- 23123346
TI  - Increased brain monoaminergic tone after the NMDA receptor GluN2A subunit gene
      knockout is responsible for resistance to the hypnotic effect of nitrous oxide.
AB  - N-methyl-d-aspartate (NMDA) receptors can be inhibited by inhalational
      anesthetics in vitro at clinically relevant concentrations. Here, to clarify the
      role of NMDA receptors in anesthetic-induced unconsciousness, we examined the
      hypnotic properties of isoflurane, sevoflurane and nitrous oxide in NMDA receptor
      GluN2A subunit knockout mice. The hypnotic properties of inhalational anesthetics
      were evaluated in mice in the loss of righting reflex (LORR) assay by measuring
      the 50% concentration for LORR (LORR ED(50)). Knockout mice displayed isoflurane
      and sevoflurane LORR ED(50) values similar to wild-type controls, indicating no
      significant contribution of these receptors to the hypnotic action of halogenated
      anesthetics. However, compared with wild-type controls, mutant mice displayed
      larger isoflurane LORR ED(50) values in the presence of nitrous oxide, indicating
      a resistance to this gaseous anesthetic. Knockout mice have enhanced brain
      monoaminergic activity which occurs secondary to NMDA receptor dysfunction, and
      the observed resistance to the isoflurane LORR ED(50)-sparing effect of nitrous
      oxide could be abolished by pretreatment with the dopamine D(2) receptor
      antagonist droperidol or with the serotonin 5-HT(2A) receptor antagonist
      ketanserin. Thus, resistance to nitrous oxide in knockout mice appears to be a
      secondary phenomenon of monoaminergic origin and not a direct result of impaired
      NMDA receptor function. Our results indicate that NMDA receptors are not
      critically involved in the hypnotic action of conventionally-used inhalational
      anesthetics. Also, they suggest that increased brain monoaminergic tone can
      diminish the effects of general anesthesia. Finally, they provide further
      evidence that changes secondary to genetic manipulation can explain the results
      obtained in global knockouts.

PMID- 23123347
TI  - Effects of the GABA(B) receptor agonist baclofen administered orally on normal
      food intake and intraperitoneally on fat intake in non-deprived rats.
AB  - It has been previously reported that the GABA(B) receptor agonist baclofen
      decreases food intake after oral administration and fat intake after
      intraperitoneal administration. The aim of the study was to investigate the
      effects of baclofen (1-4 mg/ kg) administered orally (Experiment 1) on food
      intake in non-deprived rats (n=6) and intraperitoneally (Experiment 2) on fat
      intake in non-deprived rats (n=8) that were naive to baclofen (1st set of trials)
      and in the same group of rats after they were sub-chronically exposed to baclofen
      (2nd set of trials). The results from Experiment 1 show that baclofen had no
      effects on food intake during the 1st set of trials, but the 2 and 4 mg/kg doses
      significantly increased food consumption during the 2nd set of trials. Baclofen
      produced sedation during the 1st set of trials, but tolerance occurred to this
      effect and was not apparent during the 2nd set of trials. These observations
      suggest that the motor effects may have competed with the hyperphagic effects of
      baclofen during the 1st set of trials. The data from Experiment 2 show that
      baclofen had no effects on fat intake during either the 1st or 2nd set of trials.
      The results of the study thus indicate that orally administrated baclofen
      increases food intake and intraperitoneal administration has no effect on fat
      intake in non-deprived rats under the conditions used in this study. These
      findings may have important implications for research on the use of baclofen in
      studies concerned with ingestive behaviours.

PMID- 23123348
TI  - Na(+)-H+ exchange inhibition attenuates ischemic injury in rat random pattern
      skin flap: the role of mitochondrial ATP-sensitive potassium channels.
AB  - Necrosis of distal portion of skin flaps due to ischemia still remains a problem
      in plastic surgery. Following ischemia, a cascade of deleterious events including
      over-activity of Na(+)-H(+) Exchanger (NHE) takes place. In present study we
      evaluated the effect of the potent NHE inhibitor, 5-(N-ethyl-N-isopropyl)
      amiloride (EIPA) on ischemic tissue injury in a skin flap model, and investigated
      the role of mitochondrial ATP-sensitive K(+) channels (K(ATP)) in this
      phenomenon. Seventy-eight rats were randomly divided into thirteen treatment
      groups (6 rats each). Four groups received different doses of EIPA in the flap.
      EIPA/GLY group received an effective dose of a K(ATP) channel blocker,
      glibenclamide (GLY, 0.3mg/kg) intraperitoneally (i.p.) 30 min before raising the
      flap, and a local effective dose of EIPA (0.1mM) immediately after raising the
      flap. EIPA/diazoxide group (EIPA/DIA) received a sub-effective dose of diazoxide
      (7.5mg/kg i.p.) 30 min before raising the flap and a local sub-effective dose of
      EIPA (0.075 mM). EIPA 0.1 and 0.2mM significantly increased flap survival area
      compared to control group (56.01 +/- 6.1%, P<0.001). The protective effect of
      EIPA (0.1mM) was abolished by administration of glibenclamide (0.3mg/kg i.p.). Co
      administration of a sub-effective dose of EIPA (0.075 mM), with a sub-effective
      dose of diazoxide (7.5mg/kg i.p.) significantly improved flap survival (P<0.05).
      We demonstrated that the NHE inhibitor, EIPA can increase random pattern skin
      flap survival. Administration of diazoxide potentiates this effect, while
      glibenclamide abolishes that, implicating that the protective effect of EIPA is
      mediated through mitochondrial-K(ATP) channels.

PMID- 23123349
TI  - The gamma-secretase inhibitor 2-[(1R)-1-[(4-chlorophenyl)sulfonyl](2,5
      difluorophenyl) amino]ethyl-5-fluorobenzenebutanoic acid (BMS-299897) alleviates
      Abeta1-42 seeding and short-term memory deficits in the Abeta25-35 mouse model of
      Alzheimer's disease.
AB  - Alzheimer's disease pathomimetic toxicity could be induced in mice within one
      week after the intracerebroventricular (i.c.v.) injection of an aggregated
      preparation of the highly toxic and endogenous amyloid-beta fragment Abeta(25
      35). It was recently reported that Abeta(25-35) also provokes a modification of
      APP processing with accumulation of endogenous Abeta(1-42). We here analyzed
      whether a gamma-secretase inhibitor, BMS-299897, attenuated this Abeta(25-35)
      induced Abeta(1-42) seeding and toxicity. The compound was administered at 0.1-1
      nmol/mouse, concomittantly with Abeta(25-35) (9 nmol) in male Swiss mice. After
      one week, the contents in Abeta(1-42) and Abeta(1-40), and the levels in lipid
      peroxidation were analyzed in the mouse hippocampus. Mice were submitted to
      spontaneous alternation, passive avoidance and object recognition to analyze
      their short- and long-term memory abilities. Abeta(25-35) increased Abeta(1-42)
      content (+240%) but failed to affect Abeta(1-40). BMS-299897 blocked the increase
      in Abeta(1-42) content and decreased Abeta(1-40) levels significantly. The
      compound did not affect Abeta(25-35)-induced increase in hippocampal lipid
      peroxidation. Behaviorally, BMS-299897 blocked the Abeta(25-35)-induced deficits
      in spontaneous alternation or novel object recognition, using a 1h intertrial
      time interval. BMS-299896 failed to affect the passive avoidance impairments or
      novel object recognition, using a 24h intertrial time interval. These results
      confirmed that Abeta(25-35) injection provoked an accumulation in endogenous
      Abeta(1-42), an effect blocked by gamma-secretase inhibition. This Abeta(1-42)
      accumulation marginally contributed to the toxicity or long-term memory deficits.
      However, since the seeded Abeta(1-42) affected short-term memory, the rapid
      Abeta(25-35) injection Alzheimer's disease model could be used to screen the
      activity of new secretase inhibitors.

PMID- 23123351
TI  - The GPR88 receptor agonist 2-PCCA does not alter the behavioral effects of
      methamphetamine in rats.
AB  - GPR88 is a novel orphan G protein-coupled receptor that is primarily located at
      the striatum. Genetic knockout studies reveal phenotypes of increased dopamine
      D(2) receptor sensitivity in mice, suggesting that GPR88 receptors may be
      involved in the modulation of dopaminergic system. However, there is no study
      that examines the pharmacological effects of GPR88 receptor ligands in in vivo
      preparations. This study examined the effects of a GPR88 receptor agonist, (1R,
      2R)-2-pyridin-2-yl-cyclopropane carboxylic acid ((2S, 3S)-2-amino-3-methyl
      pentyl)-(4'-propylbiphenyl-4-yl)-amide (2-PCCA), on the motor activity in rats
      and on methamphetamine-induced hyperactivity and discriminative stimulus effects.
      2-PCCA (0.1-3.2mg/kg) dose-dependently decreased the locomotor activity in rats
      and, when studied in combination with 1.0mg/kg methamphetamine, also dose
      dependently decreased methamphetamine-induced hyperactivity. However, the dose of
      2-PCCA that significantly attenuated methamphetamine-induced hyperactivity was
      also the dose that by itself markedly decreased the baseline locomotor activity.
      In rats discriminating 0.32mg/kg methamphetamine, 2-PCCA (1-3.2mg/kg) itself did
      not produce methamphetamine-like discriminative stimulus effects and, when
      studied in combination, did not alter the discriminative stimulus effects of
      methamphetamine. Together, these data have provided the first line of evidence
      that activation of GPR88 receptors does not alter the behavioral effects of
      methamphetamine. The potential implications of these findings are also discussed.

PMID- 23123350
TI  - Neuropeptide Y is analgesic in rats after plantar incision.
AB  - Previous work has demonstrated that neuropeptide tyrosine (NPY), Y(1) receptor
      and Y(2) receptor are critical in modulation of pain after nerve injury. We
      hypothesized that NPY was important for nociception after surgical incision. As a
      model of postoperative pain, rats underwent a plantar incision in one hindpaw.
      Western blots were used to quantify changes in protein expression of NPY, Y(1)
      receptor and Y(2) receptor after incision in skin, muscle, and dorsal root
      ganglion (DRG). Pain-related behaviors were tested after incision in rats treated
      with intrathecal NPY, Y(1) receptor antagonist (BIBO3304--Chemical Name: N-[(1R)
      1-[[[[4-[[(Aminocarbonyl)amino]methyl]phenyl]methyl]amino]carbonyl]-4
      [(aminoiminomethyl)amino]butyl]-alpha-phenyl-benzeneacetamide
      ditrifluoroacetate), Y(2) receptor antagonist (BIIE0246--Chemical Name: N-[(1S)-4
      [(Aminoiminomethyl)amino]-1-[[[2-(3,5-dioxo-1,2-diphenyl-1,2,4-triazolidin-4
      yl)ethyl]amino]carbonyl]butyl]-1-[2-[4-(6,11-dihydro-6-oxo-5H-dibenz[b,e]azepin
      11-yl)-1-piperazinyl]-2-oxoethyl]-cyclopentaneacetamide), combined
      NPY+antagonists, morphine, or vehicle. Pain behaviors were tested after incision
      in rats treated with locally applied intraplantar injections of NPY, Y(1)
      receptor and Y(2) receptor antagonists or vehicle. NPY protein expression was
      significantly downregulated in muscle for two days after incision. In contrast,
      Y(1) receptor and Y(2) receptor protein expression was upregulated in both skin
      and muscle. A single intrathecal injection of NPY reduced cumulative guarding
      pain scores, as did morphine. The intrathecal administration of Y(2) receptor
      antagonist also reduced pain scores; findings that were not observed when drugs
      were administered locally. Intrathecal Y(2) receptor antagonists and NPY improved
      mechanical threshold and heat withdrawal latency 2h after incision. Intrathecal
      administration of NPY and/or central blockade of Y(2) receptor attenuated pain
      behaviors early after incision (postoperative day (POD) 1-2). Y(1) receptor
      antagonist administration blocked the anti-hyperalgesic effect of NPY. Together
      these data suggest a role for spinal NPY in postoperative pain.

PMID- 23123352
TI  - Effect of dopamine and serotonin receptor antagonists on fencamfamine-induced
      abolition of latent inhibition.
AB  - The purpose of this investigation was to verify the role of dopamine and
      serotonin receptors in the effect of fencamfamine (FCF) on latent inhibition. FCF
      is a psychomotor stimulant with an indirect dopaminergic action. Latent
      inhibition is a model of attention. Latent inhibition is blocked by dopaminergic
      agents and facilitated by dopamine receptor agonists. FCF has been shown to
      abolish latent inhibition. The serotonergic system may also participate in the
      neurochemical mediation of latent inhibition. The selective dopamine D(1)
      receptor antagonist SCH 23390 (7-chloro-3-methyl-1-phenyl-1,2,4,5-tetrahydro-3
      benzazepin-8-ol), D(2) receptor antagonists pimozide (PIM) and methoclopramide
      (METH), and serotonin 5-HT(2A/C) receptor antagonist ritanserin (RIT) were used
      in the present study. Latent inhibition was evaluated using a conditioned
      emotional response procedure. Male Wistar rats that were water-restricted were
      subjected to a three-phase procedure: preexposure to a tone, tone-shock
      conditioning, and a test of the effect of the tone on licking frequency. All of
      the drugs were administered before the preexposure and conditioning phases. The
      results showed that FCF abolished latent inhibition, and this effect was clearly
      antagonized by PIM and METH and moderately attenuated by SCH 23390. At the doses
      used in the present study, RIT pretreatment did not affect latent inhibition and
      did not eliminate the effect of FCF, suggesting that the FCF-induced abolition of
      latent inhibition is not mediated by serotonin 5-HT(2A/C) receptors. These
      results suggest that the effect of FCF on latent inhibition is predominantly
      related to dopamine D(2) receptors and that dopamine D(2) receptors participate
      in attention processes.

PMID- 23123353
TI  - Microvascular filtration is increased in the forearms of patients with breast
      cancer-related lymphedema.
AB  - Breast cancer-related lymphedema (BCRL) is a frequent and debilitating
      complication of breast cancer treatment. The pathophysiology is complex and
      remains poorly understood; however, data suggest that changes in the peripheral
      circulation may contribute to edema formation. In 13 volunteers with unilateral
      BCRL, the following aspects of upper extremity peripheral circulation were
      examined: muscle relative microvascular volume; capillary filtration coefficient;
      central and local sympathetic vascular reflexes; skin blood flow; and forearm
      blood flow. These were studied via real-time, contrast-enhanced ultrasound;
      venous occlusion strain-gauge plethysmography; lower-body negative pressure;
      noninvasive blood pressure measurements; and skin (99m)Tc-pertechnetate clearance
      technique. Measurements were performed bilaterally and simultaneously in the
      forearms, enabling use of the nonedematous forearm as a control. Capillary
      filtration coefficients were additionally measured in healthy, age-matched
      controls. The capillary filtration coefficient was 7.98 +/- 2.52 MUl.100 ml(
      1).mmHg(-1).min(-1) (mean +/- SD) in edematous forearms and 6.09 +/- 1.83
      MUl.100ml.(-1).mmHg(-1).min(-1) in nonedematous forearms in the patient group (P
      < 0.001). The capillary filtration coefficient was 3.32 +/- 1.17 MUl.100ml(
      1).mmHg(-1).min(-1) in the forearms of healthy controls; significantly less than
      the both the edematous and nonedematous forearms of the patient group (P <
      0.001). No significant differences were found in muscle relative microvascular
      volume, forearm blood flow, skin blood flow, or central or local sympathetic
      vascular reflexes. Forearm microvascular filtration is increased in patients with
      BCRL, and more so in the edematous arm. The vascular sympathetic control
      mechanisms seem to be preserved. We propose that the increased capillary
      permeability may be due to low-grade inflammation promoted by reduced clearance
      of inflammatory mediators.

PMID- 23123354
TI  - Peripheral resistance: a link between global airflow obstruction and regional
      ventilation distribution.
AB  - Airflow obstruction and heterogeneities in airway constriction and ventilation
      distribution are well-described prominent features of asthma. However, the
      mechanistic link between these global and regional features has not been well
      defined. We speculate that peripheral airway resistance (R(p)) may provide such a
      link. Structural and functional parameters are estimated from PET and HRCT images
      of asthmatic (AS) and nonasthmatic (NA) subjects measured at baseline (BASE) and
      post-methacholine challenge (POST). Conductances of 35 anatomically defined
      proximal airways are estimated from airway geometry obtained from high-resolution
      computed tomography (HRCT) images. Compliances of sublobar regions subtended by
      19 most distal airways are estimated from changes in regional gas volume between
      two lung volumes. Specific ventilations (sV) of these sublobar regions are
      evaluated from 13NN-washout PET scans. For each pathway connecting the trachea to
      sublobar region, values of R(p) required to explain the sV distribution and
      global airflow obstruction are computed. Results show that R(p) is highly
      heterogeneous within each subject, but has average values consistent with global
      values in the literature. The contribution of R(p) to total pathway resistance
      (R(T)) increased substantially for POST (P < 0.0001). The fraction R(p)/R(T) was
      higher in AS than NA at POST (P < 0.0001) but similar at BASE (range: 0.960
      0.997, median: 0.990). For POST, R(p)/R(T) range was 0.979-0.999 (NA) and 0.981
      0.995 (AS). This approach allows for estimations of peripheral airway resistance
      within anatomically defined sublobar regions in vivo human lungs and may be used
      to evaluate peripheral effects of therapy in a subject specific manner.

PMID- 23123355
TI  - Examining job tenure and lost-time claim rates in Ontario, Canada, over a 10-year
      period, 1999-2008.
AB  - OBJECTIVE: We sought to examine the association between job tenure and lost-time
      claim rates over a 10-year period in Ontario, Canada. METHODS: Data were obtained
      from workers' compensation records and labour force survey data from 1999 to
      2008. Claim rates were calculated for gender, age, industry, occupation, year and
      job tenure group. A multivariate analysis and examination of effect modification
      were performed. Differences in injury event and source of injury were also
      examined by job tenure. RESULTS: Lost-time claim rates were significantly higher
      for workers with shorter job tenure, regardless of other factors. Claim rates for
      new workers differed by gender, age and industry, but remained relatively
      constant at an elevated rate over the observed time period. CONCLUSIONS: This
      study is the first to examine lost-time claim rates by job tenure over a time
      period during which overall claim rates generally declined. Claim rates did not
      show a convergence by job tenure. Findings highlight that new workers are still
      at elevated risk, and suggest the need for improved training, reducing exposures
      among new workers, promoting permanent employment, and monitoring work injury
      trends and risk factors.

PMID- 23123356
TI  - Trends in anti-infective drugs use in pregnancy.
AB  - BACKGROUND: Development of knowledge in understanding the use of anti-infective
      drugs during pregnancy has been limited by difficulties in testing medications in
      pregnant women and lack of evidence-based data. Overuse of broad spectra agents
      is associated with development and spread of bacterial resistance, a problem that
      is faced as a significant threat to the public health. OBJECTIVES: To describe
      trends in use of general and broad spectrum anti-infective drugs during
      pregnancy. METHODS: We used the Quebec Pregnancy Registry to analyse trends for
      use of oral anti-infectives dispensed during pregnancy for the five-year period
      comprised between January 1998 and December 2002. Trends in use were assessed for
      classes of anti-infectives and for broad-spectrum drugs. Descriptive statistics
      were used to summarize the characteristics of the study population. Annual trends
      for the use of anti-infective drugs were analyzed using the Cochran-Armitage
      test. RESULTS: The use of anti-infective drugs and broad spectrum agents during
      pregnancy decreased from 1998 to 2002 (p <= 0.05 for trends). The classes that
      showed increasing trend for use were: macrolides, quinolones, tetracyclines,
      urinary anti-infective drugs and antimycotics. Use of penicillins and
      sulfonamides decreased. Azithromycin showed a remarkable increase in its use:
      0.04% of all anti-infective prescriptions in 1998, compared to 10.16% in 2002.
      CONCLUSIONS: Decrease in the use of broad-spectrum drugs may have been caused by
      a positive impact of data issued from evidence in everyday life clinical
      practice. More data is needed to evaluate the impact of the knowledge transfer
      from evidence-based studies on prescription's trends during pregnancy.

PMID- 23123359
TI  - Phosphorylation of leukocyte glucocorticoid receptor in patients with current
      episode of major depressive disorder.
AB  - The impaired glucocorticoid receptor (GR) signaling has long been considered one
      of the cornerstones in understanding the pathophysiology of depression. Since the
      phosphorylation of GR is very important for GR function, in this study we
      investigated whether GR phosphorylation at serine 211 (pGR-S211) and serine 226
      (pGR-S226) is altered in patients with current episode of major depressive
      disorder (MDD). Particularly, in 30 MDD patients and 35 controls we assessed the
      levels of nuclear total GR (tGR), pGR-S211 and pGR-S226 in peripheral blood
      mononuclear cells (PBMC) using Western blot technique, along with plasma cortisol
      concentrations from the same blood samples. Our results demonstrated increased
      phosphorylation of GR at S226 (p<0.001) and, to a less extent, at S211 (p<0.05)
      in MDD patients compared to controls. Consequently, the pGR-S211/pGR-S226 ratio
      was decreased (p<0.05) implying reduced transcriptional activity of GR in MDD
      patients. MDD subjects had higher cortisol levels than controls and cortisol
      concentrations were positively correlated with PBMC pGR-S226 levels from the same
      blood samples. There was no difference in the levels of tGR between MDD and
      control subjects. The study showed that altered phosphorylation of GR could
      contribute to impaired GR function related to the pathophysiology of depression.

PMID- 23123358
TI  - Chronic in vivo load alteration induces degenerative changes in the rat
      tibiofemoral joint.
AB  - OBJECTIVE: We investigated the relationship between the magnitude and duration of
      sustained compressive load alteration and the development of degenerative changes
      in the rat tibiofemoral joint. METHODS: A varus loading device was attached to
      the left hind limb of mature rats to apply increased compression to the medial
      compartment and decreased compression to the lateral compartment of the
      tibiofemoral joint of either 0% or 100% body weight for 0, 6 or 20 weeks.
      Compartment-specific assessment of the tibial plateaus included biomechanical
      measures (articular cartilage aggregate modulus, permeability and Poisson's
      ratio, and subchondral bone modulus) and histological assessments (articular
      cartilage, calcified cartilage, and subchondral bone thicknesses, degenerative
      scoring parameters, and articular cartilage cellularity). RESULTS: Increased
      compression in the medial compartment produced significant degenerative changes
      consistent with the development of osteoarthritis (OA) including a progressive
      decrease in cartilage aggregate modulus (43% and 77% at 6 and 20 weeks),
      diminished cellularity (38% and 51% at 6 and 20 weeks), and increased
      histological degeneration. At 20 weeks, medial compartment articular cartilage
      thickness decreased 30% while subchondral bone thickness increased 32% and
      subchondral bone modulus increased 99%. Decreased compression in the lateral
      compartment increased calcified cartilage thickness, diminished region-specific
      subchondral bone thickness and revealed trends for reduced cellularity and
      decreased articular cartilage thickness at 20 weeks. CONCLUSIONS: Altered chronic
      joint loading produced degenerative changes consistent with those observed
      clinically with the development of OA and may replicate the slow development of
      non-traumatic OA in which mechanical loads play a primary etiological role.

PMID- 23123361
TI  - Innovative trends in the design of therapeutic trials in psychopharmacology and
      psychotherapy.
AB  - The standard randomized controlled trial design is still based on the acute
      disease model. This is in sharp contrast with the fact that the patient is likely
      to have experienced other treatments before, that may actually modify clinical
      course and responsiveness. The current standard of therapeutic trial in
      psychiatry is represented by the large, multi-center, controlled randomized trial
      with broad inclusion criteria, and little attention to other factors such as the
      clinical history of patients and comorbidity. The heterogeneous features of these
      patients would then affect the outcome of the trial. Conflicting results among
      randomized controlled trials can represent a spectrum of outcomes, based on
      different patient groups, more than bias or random variability. If a treatment is
      tested by a series of small trials with inclusion criteria for specific
      characteristics (including treatment history, subgroups and comorbidity), we may
      have a better knowledge of its indications and contraindications. Further, there
      is increasing need of expanding the content of customary clinical information, by
      including evaluation of variables such as stress, lifestyle, well-being, illness
      behavior and psychological symptoms. These joint strategies would actually
      constitute a paradigm shift in psychopharmacology and psychotherapy research.

PMID- 23123357
TI  - Antioxidants as potential therapeutics for neuropsychiatric disorders.
AB  - Oxidative stress has been implicated in the pathophysiology of many
      neuropsychiatric disorders such as schizophrenia, bipolar disorder, major
      depression etc. Both genetic and non-genetic factors have been found to cause
      increased cellular levels of reactive oxygen species beyond the capacity of
      antioxidant defense mechanism in patients of psychiatric disorders. These factors
      trigger oxidative cellular damage to lipids, proteins and DNA, leading to
      abnormal neural growth and differentiation. Therefore, novel therapeutic
      strategies such as supplementation with antioxidants can be effective for long
      term treatment management of neuropsychiatric disorders. The use of antioxidants
      and PUFAs as supplements in the treatment of neuropsychiatric disorders has
      provided some promising results. At the same time, one should be cautious with
      the use of antioxidants since excessive antioxidants could dangerously interfere
      with some of the protective functions of reactive oxygen species. The present
      article will give an overview of the potential strategies and outcomes of using
      antioxidants as therapeutics in psychiatric disorders. 

PMID- 23123360
TI  - Allele-specific associations of 5-HTTLPR/rs25531 with ADHD and autism spectrum
      disorder.
AB  - BACKGROUND: The aims of the present study were to examine the association between
      a common serotonin transporter gene (SLC6A4) polymorphism 5-HTTLPR/rs25531 with
      severity of attention-deficit hyperactivity disorder (ADHD) and autism spectrum
      disorder (ASD) symptoms. METHODS: Mothers and teachers completed a validated DSM
      IV-referenced rating scale for ADHD and ASD symptoms in 118 children with ASD.
      RESULTS: Analyses indicated that children with at least one copy of the S or L(G)
      allele obtained significantly more severe maternal ratings of hyperactivity
      (p=0.001; etap(2)=0.097) and impulsivity (p=0.027; etap(2)=0.044) but not
      inattention (p=0.061; etap(2)=0.032), controlling for ASD severity, than children
      homozygous for the L(A) allele. Conversely, mothers' ratings indicated that
      children with L(A)/L(A) genotype had more severe ASD social deficits than S or
      L(G) allele carriers (p=0.003; etap(2)=0.081), controlling for ADHD symptom
      severity. Teachers' ratings though consistent with mothers' ratings of
      hyperactivity and social deficits were marginally significant (p=0.07/p=0.09).
      There was some evidence that the magnitude of parent-teacher agreement regarding
      symptom severity varied as a function of the child's genotype. CONCLUSION: The 5
      HTTLPR/rs25531 polymorphism or its correlates may modulate severity of ADHD and
      ASD symptoms in children with ASD, but in different ways. These tentative,
      hypothesis-generating findings require replication with larger independent
      samples.

PMID- 23123362
TI  - Neural mechanism of placebo effects and cognitive reappraisal in emotion
      regulation.
AB  - The present study compared learning-based placebo effect and cognition-based
      reappraisal, to reveal the common and unique neural mechanisms between the two
      emotion regulations. First, the anxiety-relieving effect was tested by conducting
      a behavioral experiment. Next, the participants with the highest placebo or
      reappraisal effect were selected for the functional magnetic resonance imaging
      experiments. The results indicated that: (1) they both attenuated activity in the
      right amygdala and right insula, and (2) placebo effect activated the left
      subgenual cingulate whereas reappraisal activated the right dorsal prefrontal
      cortex (PFC) and the left inferior PFC. Our results show that learning-based
      placebo effect and cognition-based reappraisal have common anxiety-relieving
      effects. The placebo effect mainly depends on direct pathway subgenual cingulate
      amygdala to regulate emotions, whereas the reappraisal may rely on both indirect
      pathways, such as the dorsal PFC-subgenual cingulate-amygdala, and direct
      pathways, such as the ventral lateral PFC-amygdala to regulate emotions.

PMID- 23123363
TI  - Neuropsychological functioning and age-related changes in schizophrenia and/or
      cocaine dependence.
AB  - Although little is known about the combined effects of Schizophrenia (SZ) and
      Substance Use Dependence (SUD) in neurocognitive functioning, the current
      literature points out that performance depends on the specific cognitive domains,
      the age of individuals and the type of substance of abuse. Our aim is to
      elucidate, in a sample with SZ and/or cocaine dependent individuals in remission
      for more than 4 months, their performance in attention, verbal memory and speed
      of processing, taking into account the possible effect of both age and duration
      of SUD. The total sample consisted of 95 male patients, aged 20 to 60 years,
      divided in three groups: one group with SZ and cocaine dependence (SZ+), another
      group with SZ without cocaine dependence (SZ-) and a third group with cocaine
      dependence without psychiatric comorbidity (COC). Our results show that those SZ+
      who were abstinent for more than four months did not differ from their SZ-
      counterparts in the neuropsychological functioning. Both SZ groups performed
      significantly worse than the COC group. A negative impact of age on the
      neuropsychological performance was found in the SZ+ group, suggesting additive
      later cognitive deficits in SZ+ patients due to the long-term brain damage of
      SUD.

PMID- 23123366
TI  - Fabrication of nanoporous carbon by electrical transformation of amorphous carbon
      nanospheres.
AB  - Nanoporous carbon nanospheres <150 nm in diameter have been fabricated for the
      first time by the transformation of amorphous carbon nanospheres under Joule
      heating. The process, initiated by current densities of 1.5-8 * 10(10) A m(-2),
      has been imaged in real time in situ in a transmission electron microscope.
      Significant atomic diffusion and carbon ordering results in the formation of a 3D
      network of buckled graphitic sheets bounding interlinked <5 nm diameter pores,
      with greatly enhanced conductivity. Porous carbon nanospheres offer new
      opportunities for biocompatible drug delivery, catalysis and energy storage.

PMID- 23123365
TI  - The role of pro-inflammatory cytokines in the neuroinflammation and neurogenesis
      of schizophrenia.
AB  - Schizophrenia is a serious mental illness with chronic symptoms and significant
      impairment in psychosocial functioning. Although novel antipsychotics have been
      developed, the negative and cognitive symptoms of schizophrenia are still
      unresponsive to pharmacotherapy. The high level of social impairment and a
      chronic deteriorating course suggest that schizophrenia likely has
      neurodegenerative characteristics. Inflammatory markers such as pro-inflammatory
      cytokines are well-known etiological factors for psychiatric disorders, including
      schizophrenia. Inflammation in the central nervous system is closely related to
      neurodegeneration. In addition to pro-inflammatory cytokines, microglia also play
      an important role in the inflammatory process in the CNS. Uncontrolled activity
      of pro-inflammatory cytokines and microglia can induce schizophrenia in tandem
      with genetic vulnerability and glutamatergic neurotransmitters. Several studies
      have investigated the possible effects of antipsychotics on inflammation and
      neurogenesis. Additionally, anti-inflammatory adjuvant therapy has been under
      investigation as a treatment option for schizophrenia. Further studies should
      consider the confounding effects of systemic factors such as metabolic syndrome
      and smoking. In addition, the unique mechanisms by which pro-inflammatory
      cytokines are involved in the etiopathology of schizophrenia should be
      investigated. In this article, we aimed to review (1) major findings regarding
      neuroinflammation and pro-inflammatory cytokine alterations in schizophrenia, (2)
      interactions between neuroinflammation and neurogenesis as possible neural
      substrates for schizophrenia, and (3) novel pharmacological approaches. 

PMID- 23123364
TI  - Potential translational targets revealed by linking mouse grooming behavioral
      phenotypes to gene expression using public databases.
AB  - Rodent self-grooming is an important, evolutionarily conserved behavior, highly
      sensitive to pharmacological and genetic manipulations. Mice with aberrant
      grooming phenotypes are currently used to model various human disorders.
      Therefore, it is critical to understand the biology of grooming behavior, and to
      assess its translational validity to humans. The present in-silico study used
      publicly available gene expression and behavioral data obtained from several
      inbred mouse strains in the open-field, light-dark box, elevated plus- and
      elevated zero-maze tests. As grooming duration differed between strains, our
      analysis revealed several candidate genes with significant correlations between
      gene expression in the brain and grooming duration. The Allen Brain Atlas,
      STRING, GoMiner and Mouse Genome Informatics databases were used to functionally
      map and analyze these candidate mouse genes against their human orthologs,
      assessing the strain ranking of their expression and the regional distribution of
      expression in the mouse brain. This allowed us to identify an interconnected
      network of candidate genes (which have expression levels that correlate with
      grooming behavior), display altered patterns of expression in key brain areas
      related to grooming, and underlie important functions in the brain. Collectively,
      our results demonstrate the utility of large-scale, high-throughput data-mining
      and in-silico modeling for linking genomic and behavioral data, as well as their
      potential to identify novel neural targets for complex neurobehavioral
      phenotypes, including grooming.

PMID- 23123367
TI  - Dispositional depression and hostility are associated with inflammatory markers
      of cardiovascular disease in African Americans.
AB  - Prior research has demonstrated that state depressive symptoms and hostility can
      modulate inflammatory immune responses and directly contribute to cardiovascular
      disease (CVD) onset and development. Previous studies have not considered the
      contribution of dispositional depressive symptoms to the inflammatory process.
      They have also largely excluded African Americans, despite their disproportionate
      risk for CVD. The first aim of the study was to examine the impact of state and
      dispositional depression and hostility on CVD-associated inflammatory biomarkers
      interleukin-6 (IL-6) and C-reactive protein (CRP) in an African American sample.
      The second aim was to examine synergistic influences of hostility and state and
      dispositional depression on IL-6 and CRP. The final aim was to examine whether
      the relations between state and dispositional depression, hostility, IL-6, and
      CRP varied as a function of gender and education. Anthropometric measures, blood
      serum samples, and psychosocial data were collected from 198 African Americans
      from the Washington, DC metropolitan area. Hierarchical and stepwise regression
      analyses indicated that (1) increased levels of hostility were associated with
      increased levels of CRP; (2) hostility and IL-6 were more strongly associated
      among participants with lower educational attainment; and (3) dispositional
      depression and CRP were more strongly associated among participants with greater
      hostility and lower educational attainment. Findings suggest that enduring
      personality dispositions, such as dispositional depression and hostility, are
      critical to a thorough assessment of cardiovascular profiles in African
      Americans. Future studies should investigate causal pathways that link depressive
      and hostile personality styles to inflammatory activity for African American men
      and women.

PMID- 23123368
TI  - Prognostic risk stratification of patients with urothelial carcinoma of the
      bladder with recurrence after radical cystectomy.
AB  - PURPOSE: We identify clinicopathological variables predicting overall survival in
      patients with recurrent bladder urothelial carcinoma after radical cystectomy.
      MATERIALS AND METHODS: We retrospectively collected data on 114 patients treated
      with radical cystectomy for bladder urothelial carcinoma who subsequently had
      remote metastasis and/or local recurrence. The Kaplan-Meier method with the log
      rank test and multivariate Cox regression models were used to address overall
      survival after recurrence. RESULTS: During followup 99 of the 114 patients died.
      Median survival in the 114 patients was 11.2 months. One and 3-year overall
      survival rates were 48.0% and 12.1%, respectively. On multivariate analysis
      independent predictors of poorer overall survival included less than 1 year to
      recurrence, symptoms at recurrence, 2 or more metastatic organs at recurrence,
      high serum C-reactive protein, high lactate dehydrogenase, no post-recurrence
      platinum based chemotherapy and no metastasectomy. Based on the 4 variables (time
      to recurrence, symptoms, number of metastatic organs and C-reactive protein), we
      constructed a risk model predicting post-recurrence overall survival that
      classified patients into 3 groups with significantly different overall survival
      (p <0.0001). CONCLUSIONS: Our data confirm that recurrent urothelial carcinoma
      after radical cystectomy is a highly aggressive, lethal disease. Seven
      clinicopathological factors were identified that predicted post-recurrence
      overall survival. Our risk model based on the 4 variables could be useful to
      provide relevant prognostic information to patients and physicians, and better
      stratify patients in clinical trials.

PMID- 23123369
TI  - Functional defecation disorders in children with lower urinary tract symptoms.
AB  - PURPOSE: We assessed the prevalence of functional defecation disorders, such as
      functional constipation and functional nonretentive fecal incontinence, in
      children referred to a tertiary pediatric urology outpatient clinic for lower
      urinary tract symptoms. MATERIALS AND METHODS: We reviewed the charts of 4 to 17
      year-old patients evaluated due to lower urinary tract symptoms. All patients
      received a standardized bowel questionnaire and physical examination. We assessed
      the prevalence of pediatric functional defecation disorders according to Rome III
      criteria. Transabdominal ultrasound was performed to measure rectal diameter with
      a diameter of greater than 3 cm considered to indicate a rectal fecal mass.
      RESULTS: We analyzed the records of 113 patients, including 50 boys, with a
      median age of 8 years (IQR 6-10) who had lower urinary tract symptoms. Of the
      patients 46 had dysfunctional voiding and 38 had urge incontinence/overactive
      bladder. Rome III criteria for functional constipation and functional
      nonretentive fecal incontinence were fulfilled by 47% and 11% of patients with
      lower urinary tract symptoms, respectively. Children with dysfunctional voiding
      were more likely to fulfill the criteria for functional constipation than those
      with urge incontinence and other urological disorders (63% vs 42% and 28%,
      respectively, p = 0.009). Children with urge incontinence more likely fulfilled
      the criteria for functional nonretentive fecal incontinence than those with
      dysfunctional voiding and other urological disorders (21% vs 2.2% and 10%,
      respectively, p = 0.02). CONCLUSIONS: More than 50% of children with lower
      urinary tract symptoms evaluated at a tertiary referral center fulfilled the
      diagnostic criteria for functional defecation disorders. We recommend evaluating
      bowel habits as part of the initial assessment of a child who presents with
      urological symptoms. Future studies of the effect on urological symptoms of
      treating functional defecation disorders are justified.

PMID- 23123370
TI  - Myoblasts inhibit prostate cancer growth by paracrine secretion of tumor necrosis
      factor-alpha.
AB  - PURPOSE: Myoblasts can form muscle fibers after transplantation. Therefore, they
      are envisioned as a treatment for urinary incontinence after radical
      prostatectomy. However, to our knowledge the safety of this treatment and the
      interaction of myoblasts with any remaining neighboring cancer are unknown. We
      investigated the interactions between myoblasts and prostate carcinoma cells in
      vitro and in vivo. MATERIALS AND METHODS: Myoblasts isolated from the rectus
      abdominis were used in a series of co-culture experiments with prostate cancer
      cells and subcutaneously co-injected in vivo. Cell proliferation, cell cycle
      arrest and apoptosis of cancer in co-culture with myoblasts were assessed. Tumor
      volume and metastasis formation were evaluated in a mouse model. Tissue specific
      markers were assessed by immunohistochemistry, fluorescence activated cell
      sorting analysis, Western blot and real-time quantitative polymerase chain
      reaction. RESULTS: Myoblasts in proximity to tumor provided paracrine tumor
      necrosis factor-alpha to their microenvironment, decreasing the tumor growth of
      all prostate cancer cell lines examined. Co-culture experiments revealed
      induction of cell cycle arrest, tumor death by apoptosis and increased myoblast
      differentiation. This effect was largely blocked by tumor necrosis factor-alpha
      inhibition. The same outcome was noted in a mouse model, in which co-injected
      human myoblasts also inhibited the tumor growth and metastasis formation of all
      prostate cancer cell lines evaluated. CONCLUSIONS: Myoblasts restrict prostate
      cancer growth and limit metastasis formation by paracrine tumor necrosis factor
      alpha secretion in vitro and in vivo.

PMID- 23123371
TI  - Long-term survival outcomes with intravesical docetaxel for recurrent nonmuscle
      invasive bladder cancer after previous bacillus Calmette-Guerin therapy.
AB  - PURPOSE: Docetaxel is a safe agent for intravesical therapy. Adding monthly
      maintenance treatments can extend response durability. We report our cumulative
      experience with intravesical docetaxel in a larger cohort with extended followup.
      MATERIALS AND METHODS: A total of 54 patients received salvage intravesical
      docetaxel for bacillus Calmette-Guerin refractory nonmuscle invasive bladder
      cancer between 2003 and 2012, including 18 treated during the original phase I
      trial. All patients received 6 weekly instillations of intravesical docetaxel.
      After the phase I trial, those with a complete response to induction treatment
      were offered single dose monthly maintenance treatments for a total of up to 12
      months of docetaxel therapy. Recurrence was defined as positive biopsy or urine
      cytology. Recurrence-free, disease specific and overall survival was determined
      by Kaplan-Meier analysis. RESULTS: Median followup was 39.1 months. Of the 54
      patients 32 (59%) had a complete initial response after induction therapy,
      including 18 who received additional monthly maintenance treatments. Median time
      to recurrence in initial responders treated with vs without docetaxel maintenance
      was 39.3 vs 19.0 months. One and 3-year recurrence-free survival rates for the
      entire cohort were 40% and 25%, respectively. Of the 54 patients 17 (24%)
      underwent radical cystectomy at a median of 24 months of followup. Five-year
      disease specific and overall survival rates were 85% and 71%, respectively.
      CONCLUSIONS: Intravesical docetaxel appears to be a promising agent with
      significant efficacy and durability for bacillus Calmette-Guerin refractory
      nonmuscle invasive bladder cancer. Adding maintenance treatments may increase the
      duration of recurrence-free survival.

PMID- 23123372
TI  - Operational characteristics of (11)c-choline positron emission
      tomography/computerized tomography for prostate cancer with biochemical
      recurrence after initial treatment.
AB  - PURPOSE: We examined the performance of (11)C-choline positron emission
      tomography/computerized tomography for its ability to delineate prostate cancer
      distribution and extent after initial therapy. MATERIALS AND METHODS: A
      consecutive series retrospective review was performed of all patients with
      prostate cancer who were evaluated using (11)C-choline positron emission
      tomography/computerized tomography from September 2007 to November 2010 at the
      Mayo Clinic. Statistical analysis was performed to determine the sensitivity,
      specificity, positive predictive value, negative predictive value and prostate
      specific antigen threshold for the detection of recurrent lesions. RESULTS: In
      the study period 176 patients with biochemical recurrence after primary treatment
      failure underwent (11)C-choline positron emission tomography/computerized
      tomography. Using patient based analysis (11)C-choline positron emission
      tomography yielded a sensitivity, specificity, positive predictive value and
      negative predictive value of 93%, 76%, 91% and 81%, respectively. Of the 176
      positron emission tomography/computerized tomography scans performed 56 (32%)
      were deemed clinically useful as defined by the ability to identify lesions not
      delineated using conventional imaging, thereby prompting changes in clinical
      management. The optimal prostate specific antigen for lesion detection was 2.0
      ng/ml. On multivariate analysis prostate specific antigen at positron emission
      tomography (HR 1.37, p = 0.04) and clinical stage at initial diagnosis of
      prostate cancer (HR 5.19, p = 0.0035) were significant predictors of positive
      (11)C-choline positron emission tomography/computerized tomography. CONCLUSIONS:
      (11)C-choline positron emission tomography/computerized tomography performs well
      in men with biochemical recurrence after primary treatment failure. The optimal
      prostate specific antigen value for lesion detection is approximately 2.0 ng/ml.
      We found that (11)C-choline positron emission tomography/computerized tomography
      substantially enhances the rate of prostate cancer lesion detection by
      approximately 32% beyond what can be garnered using conventional imaging
      techniques and at a lower prostate specific antigen value.

PMID- 23123373
TI  - Laparoscopic pyeloplasty for ureteropelvic junction obstruction in infants.
AB  - PURPOSE: Laparoscopic pyeloplasty and open pyeloplasty have comparable efficacy
      for ureteropelvic junction obstruction in pediatric patients. The role of
      laparoscopic pyeloplasty in infants is less well defined. We present our updated
      experience with laparoscopic pyeloplasty in children younger than 1 year.
      MATERIALS AND METHODS: We retrospectively reviewed the records of all 29 infants
      treated with transperitoneal laparoscopic pyeloplasty for symptomatic and/or
      radiographic ureteropelvic junction obstruction from May 2005 to February 2012.
      Patients were followed with renal ultrasound at regular intervals. Treatment
      failure was defined as the inability to complete the intended procedure,
      persistent radiographic evidence of obstruction and/or the need for definitive
      adjunctive procedures. RESULTS: Transperitoneal laparoscopic pyeloplasty was
      performed in 29 infants 2 to 11 months old (mean age 6.0 months) weighing 4.1 to
      10.9 kg (mean +/- SD 7.9 +/- 1.6). Followup was available in all except 5
      patients (median 13.9 months, IQR 7.7-23.8). Mean operative time was 245 +/- 44
      minutes. All cases were completed laparoscopically. Three postoperative
      complications were reported, including ileus, superficial wound infection and
      pyelonephritis. Two patients had persistent symptomatic and/or radiographic
      evidence of obstruction, and required reoperative pyeloplasty. The overall
      success rate was 92%. CONCLUSIONS: Laparoscopic pyeloplasty in infants remains a
      technically challenging procedure limited to select centers. Our early experience
      revealed a success rate comparable to that of other treatment modalities with
      minimal morbidity.

PMID- 23123374
TI  - The surgical learning curve of artificial urinary sphincter implantation:
      implications for prosthetic training and referral.
AB  - PURPOSE: We investigated the surgical learning curve of artificial urinary
      sphincter implantation using a large, consecutive, single surgeon series.
      MATERIALS AND METHODS: We retrospectively reviewed the results of the first 150
      consecutive, virgin artificial urinary sphincter implantations performed by a
      single surgeon between 1992 and 2003 for post-prostatectomy male stress urinary
      incontinence. Complication and reoperation rates, and continence outcomes (daily
      pad use and number of patients with a functional artificial urinary sphincter at
      last followup) were analyzed as a function of consecutive implant cases. RESULTS:
      There was a significant decrease in the number of patients with complications (12
      vs 3, relative risk 4.0, p = 0.012) and the number with reoperation (11 vs 3,
      relative risk 3.7, p = 0.026) when the first 25 patients who underwent artificial
      urinary sphincter implantation were compared to the second 25. No further
      decrease was noted beyond the first 25 cases. Despite significantly higher
      complication and reoperation rates in the first 25 cases, equivalent functional
      outcomes (same postoperative daily pad use and number of patients with a
      functional artificial urinary sphincter at last followup) were still achieved
      after artificial urinary sphincter revision. CONCLUSIONS: The surgical learning
      curve of placing a virgin artificial urinary sphincter was about 25 cases, as
      measured by complication and reoperation rates. This case number was high
      compared to typical exposure during residency and clinical practice. There is an
      urgent need to improve urological prosthetic training and emphasize the referral
      of artificial urinary sphincter cases to regional centers of excellence or to
      high volume, artificial urinary sphincter implanters to improve the surgical
      outcome.

PMID- 23123376
TI  - Tranexamic acid reduces blood loss during percutaneous nephrolithotomy: a
      prospective randomized controlled study.
AB  - PURPOSE: Bleeding is a significant morbidity associated with percutaneous
      nephrolithotomy. This study was conducted to evaluate the safety and efficacy of
      the antifibrinolytic agent tranexamic acid in reducing blood loss in patients
      undergoing percutaneous nephrolithotomy. MATERIALS AND METHODS: A total of 200
      patients undergoing percutaneous nephrolithotomy were randomized into 2 equal
      groups. Patients in the tranexamic acid group received 1 gm tranexamic acid at
      induction followed by 3 oral doses of 500 mg during 24 hours, while those in the
      control group did not receive tranexamic acid. The patient demographics and
      clinical data of the 2 groups were compared. RESULTS: Baseline patient
      demographics were similar in both groups. Mean hemoglobin decrease in the
      tranexamic acid group was significantly lower than that of the control group
      (1.39 vs 2.31 gm/dl, p <0.0001). Mean operative time in the tranexamic acid group
      was significantly lower than that in the control group (48.3 vs 70.8 minutes, p
      <0.0001). The stone clearance rate was similar in both groups (91% vs 82%, p =
      0.06). The blood transfusion rate was lower in the tranexamic acid group (2% vs
      11%, p = 0.018), as was the complication rate (33% vs 59%, p <0.0001). Two
      patients with a solitary functioning kidney in the tranexamic acid group required
      ureteral stenting to relieve anuria due to clot obstruction. CONCLUSIONS: The use
      of tranexamic acid in percutaneous nephrolithotomy is safe, and is associated
      with reduced blood loss and a lower complication rate.

PMID- 23123375
TI  - Randomized controlled trial of oxybutynin extended release versus placebo for
      urinary symptoms during intravesical Bacillus Calmette-Guerin treatment.
AB  - PURPOSE: Intravesical bacillus Calmette-Guerin is used to decrease recurrence
      rates of nonmuscle invasive urothelial carcinoma. Irritative urinary symptoms are
      a common side effect of treatment and frequently limit treatment tolerance. While
      anticholinergic medications may be used for symptom prophylaxis, to our knowledge
      they have not been evaluated in a randomized controlled trial. MATERIALS AND
      METHODS: A total of 50 bacillus Calmette-Guerin naive patients were randomized to
      10 mg extended release oxybutynin daily or placebo starting the day before 6
      weekly bacillus Calmette-Guerin treatments. A questionnaire assessing urinary
      symptoms (frequency, burning on urination, urgency, bladder pain, hematuria),
      systemic symptoms (flu-like symptoms, fever, arthralgia) and medication side
      effects (constipation, blurred vision, dry mouth) was recorded daily throughout
      the therapeutic course. A linear mixed repeated measures model tested the
      differences between each point and baseline score. RESULTS: The treatment group
      had a greater increase in urinary frequency and burning on urination compared to
      placebo (p = 0.004 and p = 0.04, respectively). There were no significant
      differences between groups for other urinary symptoms, which increased in
      severity after bacillus Calmette-Guerin but concomitantly returned to baseline in
      both groups. The treatment group experienced increases in fever, flu-like
      symptoms, dry mouth and constipation compared to placebo (p <0.0001, p = 0.0008,
      p = 0.045 and p = 0.001, respectively). There were otherwise no significant
      differences in nonurinary symptoms or medication adverse reactions. CONCLUSIONS:
      Oxybutynin increased urinary frequency and burning on urination compared to
      placebo in patients receiving intravesical bacillus Calmette-Guerin treatment.
      Our results do not support the routine use of oxybutynin as prophylaxis against
      urinary symptoms during bacillus Calmette-Guerin therapy.

PMID- 23123377
TI  - Percutaneous renal cryoablation after partial nephrectomy: technical feasibility,
      complications and outcomes.
AB  - PURPOSE: Treatment of locally recurrent or de novo tumors in the ipsilateral
      kidney after partial nephrectomy represents a management dilemma. Percutaneous
      renal cryoablation offers a minimally invasive treatment option in such cases. We
      review our single institution experience with percutaneous cryoablation of renal
      tumors after partial nephrectomy for technical feasibility, complications and
      outcomes. MATERIALS AND METHODS: Between March 2003 and January 2012, 48 patients
      underwent percutaneous cryoablation for the treatment of 68 ipsilateral renal
      tumors after previous partial nephrectomy. Oncologic outcomes, complications
      (Clavien-Dindo classification system) and renal function were evaluated. RESULTS:
      Median maximal diameter of the treated renal tumors was 2.5 cm (range 1.2 to
      5.4). All cryoablation procedures were considered technically successful. Of the
      54 biopsy proven or suspected renal cell carcinomas with 3 or more months of
      computerized tomography/magnetic resonance imaging followup after cryoablation
      (median 19, range 3 to 61), 5 cases (9.3%) had local tumor recurrence. Major
      (grade 3 or greater) complications developed after 3 (5.7%) cryoablation
      procedures and there were no perioperative deaths. Median change in patient
      estimated glomerular filtration rate after renal cryoablation was -1.5 ml per
      minute. No patients required dialysis in the perioperative period, while 2 with
      stage 4 chronic kidney disease at the time of ablation became dialysis dependent
      at 5 and 23 months after treatment, respectively. CONCLUSIONS: Percutaneous renal
      cryoablation after ipsilateral partial nephrectomy is technically feasible, has a
      low rate of major complications, provides relative preservation of renal function
      and demonstrates acceptable short-term oncologic outcomes in this challenging
      population.

PMID- 23123378
TI  - Reverse gyrase transiently unwinds double-stranded DNA in an ATP-dependent
      reaction.
AB  - Reverse gyrase is a unique DNA topoisomerase that catalyzes the introduction of
      positive supercoils into DNA in an ATP-dependent reaction. It consists of a
      helicase domain that functionally cooperates with a topoisomerase domain.
      Different models for the catalytic mechanism of reverse gyrase that predict a
      central role of the helicase domain have been put forward. The helicase domain
      acts as a nucleotide-dependent conformational switch that alternates between open
      and closed states with different affinities for single- and double-stranded DNA.
      It has been suggested that the helicase domain can unwind double-stranded
      regions, but helicase activity has not been demonstrated as yet. Here, we show
      that the isolated helicase domain and full-length reverse gyrase can transiently
      unwind double-stranded regions in an ATP-dependent reaction. The latch region of
      reverse gyrase, an insertion into the helicase domain, is required for DNA
      supercoiling. Strikingly, the helicase domain lacking the latch cannot unwind
      DNA, linking unwinding to DNA supercoiling. The unwinding activity may provide
      and stabilize the single-stranded regions required for strand passage by the
      topoisomerase domain, either de novo or by expanding already existing unpaired
      regions that may form at high temperatures.

PMID- 23123380
TI  - Blunt vs. sharp uterine expansion at lower segment cesarean section delivery: a
      systematic review with metaanalysis.
AB  - OBJECTIVE: Blunt vs sharp expansion of the uterine incision at cesarean delivery
      has been investigated as a technique primarily to reduce intraoperative blood
      loss. The objective of this systematic review was to compare the effects of
      either intervention on maternal outcomes. STUDY DESIGN: A systematic review with
      metaanalyses that used the DerSimonian and Laird random effects model was
      performed. The Cochrane Central Register of Controlled Trials (The Cochrane
      Library 2012, Issue 4), MEDLINE (1948-Apr 2012), EMBASE (1947-Apr 2012), and the
      reference lists/citation history of articles were searched. Only randomized
      controlled trials were included. RESULTS: Four trials (1731 patients) were
      evaluated. Data from one recently completed trial (535 patients) were not yet
      available. Metaanalyses revealed a trend towards reduced maternal blood loss with
      blunt expansion of the uterine incision that was statistically significant when
      measured by surgeon's estimation of volume lost, but not by comparison of pre-
      and postoperative hematocrit and hemoglobin levels or a requirement for blood
      transfusion. There was a trend towards fewer unintended extensions in the blunt
      group and no difference in the incidence of endometritis. CONCLUSION: Blunt
      dissection of the uterine incision at cesarean delivery appears to be superior to
      sharp dissection in minimizing maternal blood loss. However, this conclusion
      could change when data from a new unpublished large trial are available.

PMID- 23123381
TI  - The diagnostic criteria for gestational diabetes: to change or not to change?
AB  - The different screening and diagnostic methods for gestational diabetes mellitus
      (GDM) currently in clinical use have led the National Institutes of Health Office
      of Disease Prevention to organize a consensus conference to better understand the
      potential ramifications of changing the current screening and diagnostic criteria
      in the United States vs keeping current practices in place. Research has
      demonstrated that even mild forms of hyperglycemia potentially pose significant
      adverse health consequences for pregnant women and their children. Thus, it is
      anticipated that lowering the diagnostic criteria for GDM will significantly
      reduce morbidity and health care costs in the long term. However, such a change
      would dramatically increase the number of women identified as having this disease
      and place a significantly greater burden on an already overburdened primary
      health care system. Although several cost-benefit analyses suggest that such a
      change will improve health outcomes for mothers and babies, at least 1 study
      found that these anticipated public health benefits will not occur unless a
      higher level of care is devoted to these newly diagnosed patients. There also is
      a distinct possibility that changing the diagnostic criteria for GDM will
      increase cesarean delivery rates, which might offset many of the public health
      gains engendered by diagnosing more women with this condition. The scientific
      dilemma to change or not to change, thus, requires a rigorous analysis of the
      scientific, economic, practice, and legal pros and cons to achieve a satisfactory
      answer.

PMID- 23123379
TI  - Structural mechanism of GAF-regulated sigma(54) activators from Aquifex aeolicus.
AB  - The sigma subunits of bacterial RNA polymerase occur in many variant forms and
      confer promoter specificity to the holopolymerase. Members of the sigma(54)
      family of sigma subunits require the action of a 'transcriptional activator'
      protein to open the promoter and initiate transcription. The activator proteins
      undergo regulated assembly from inactive dimers to hexamers that are active
      ATPases. These contact sigma(54) directly and, through ATP hydrolysis, drive a
      conformational change that enables promoter opening. sigma(54) activators use
      several different kinds of regulatory domains to respond to a wide variety of
      intracellular signals. One common regulatory module, the GAF domain, is used by
      sigma(54) activators to sense small-molecule ligands. The structural basis for
      GAF domain regulation in sigma(54) activators has not previously been reported.
      Here, we present crystal structures of GAF regulatory domains for Aquifex
      aeolicus sigma(54) activators NifA-like homolog (Nlh)2 and Nlh1 in three
      functional states-an 'open', ATPase-inactive state; a 'closed', ATPase-inactive
      state; and a 'closed', ligand-bound, ATPase-active state. We also present small
      angle X-ray scattering data for Nlh2-linked GAF-ATPase domains in the inactive
      state. These GAF domain dimers regulate sigma(54) activator proteins by holding
      the ATPase domains in an inactive dimer conformation. Ligand binding of Nlh1
      dramatically remodels the GAF domain dimer interface, disrupting the contacts
      with the ATPase domains. This mechanism has strong parallels to the response to
      phosphorylation in some two-component regulated sigma(54) activators. We describe
      a structural mechanism of GAF-mediated enzyme regulation that appears to be
      conserved among humans, plants, and bacteria.

PMID- 23123382
TI  - Effect of umbilical cord milking in term and near term infants: randomized
      control trial.
AB  - OBJECTIVE: The objective of the study was to investigate the effect of umbilical
      cord milking as compared with early cord clamping on hematological parameters at
      6 weeks of age among term and near term neonates. STUDY DESIGN: This was a
      randomized control trial. Eligible neonates (>35 weeks' gestation) were
      randomized in intervention and control groups (100 each). Neonates of both groups
      got early cord clamping (within 30 seconds). The cord of the experimental group
      was milked after cutting and clamping at 25 cm from the umbilicus, whereas in
      control group cord was clamped near (2-3 cm) the umbilicus and not milked. Both
      groups got similar routine care. Unpaired Student t and Fisher exact tests were
      used for statistical analysis. RESULTS: Baseline characteristics were comparable
      in the 2 groups. Mean hemoglobin (Hgb) (11.9 [1.5] g/dL and mean serum ferritin
      355.9 [182.6] MUg/L) were significantly higher in the intervention group as
      compared with the control group (10.8 [0.9] g/dL and 177.5 [135.8] MUg/L),
      respectively, at 6 weeks of age. The mean Hgb and hematocrit at 12 hours and 48
      hours was significantly higher in intervention group (P = .0001). The mean blood
      pressure at 30 minutes, 12 hours, and 48 hours after birth was significantly
      higher but within normal range. No significant difference was observed in the
      heart rate, respiratory rate, polycythemia, serum bilirubin, and need of
      phototherapy in the 2 groups. CONCLUSION: Umbilical cord milking is a safe
      procedure and it improved Hgb and iron status at 6 weeks of life among term and
      near term neonates.

PMID- 23123383
TI  - Alternative Bayesian accounts of autistic perception: comment on Pellicano and
      Burr.

PMID- 23123384
TI  - The effect of a cognitive treatment program for male and female juvenile
      offenders.
AB  - This study assessed the effectiveness of a cognitive intervention treatment
      program for juvenile offenders, which is called the Juvenile Cognitive
      Intervention Program. The program was provided to incarcerated delinquents at
      three juvenile correctional facilities in Wisconsin. The results indicated that
      using the How I Think (HIT) Questionnaire as a measure of change, significant
      improvement in reducing cognitive distortions were found across age groups and
      gender, and included individuals who were unable to successfully complete the
      program the first time and then completed it successfully. The HIT is a measure
      of cognitive distortions that are associated with delinquent thinking patterns
      and behavior. Cognitive change is a major focus of treatment programs in juvenile
      corrections as there has been substantive research demonstrating a link to
      reduced delinquent and later criminal behavior. 

PMID- 23123385
TI  - Identifying personality subtypes based on the five-factor model dimensions in
      male prisoners: implications for psychopathy and criminal offending.
AB  - The current study was designed to identify personality subtypes on the basis of
      the five-factor model dimensions in male prisoners. Participants included 110
      Flemish male prisoners assessed by means of the Neuroticism, Extraversion,
      Openness Five Factor Inventory and different symptom, personality, and coping
      measures. We found two clusters: an emotionally stable/resilient cluster and an
      aggressive/undercontrolled cluster. Prisoners within the
      aggressive/undercontrolled cluster scored significantly higher on almost all
      Minnesota Multiphasic Personality Inventory-2 basic scales, (in)direct aggression
      measures, and depressive coping scales compared with resilients. They also scored
      higher on drug abuse and committed more sexual offenses than resilient prisoners.
      These two personality subtypes bear theoretically and practically important
      implications for psychopathy subtypes and different pathways to criminal
      offenses. 

PMID- 23123386
TI  - Caffeine's effects on attentional networks in healthy subjects: a pharmacological
      functional magnetic resonance imaging study.

PMID- 23123387
TI  - Quantitative analysis with atomic force microscopy of cisplatin-induced
      morphological changes in HeLa and Ishikawa cells.
AB  - Because the cell membrane is an important regulator of cell function, its
      morphological changes are important markers of cell apoptosis. These changes can
      differ for each cell type, and depend on the treatment conditions, including the
      drug, doses, and treatment time. To quantify morphological changes, HeLa and
      Ishikawa cells were investigated with atomic force microscopy. Both cells were
      treated with cisplatin (1 mM) for 24 hours. The viability and proliferation of
      the cells were analyzed with methylthiazol tetrazolium method. The proliferation
      rates of both cells treated with cisplatin decreased more than 50%. The
      morphological changes induced by cisplatin were dependent on the cell type, and
      the results were determined quantitatively. The surface of HeLa cells became
      rougher with cisplatin treatment, whereas cisplatin-treated Ishikawa cells were
      smoother than untreated cells. In both cases, cell height was decreased with
      cisplatin treatment. These results suggest that atomic force microscopy can be
      used to analyze anticancer drug activity in cancer cells.

PMID- 23123388
TI  - Microsurgical medial fenestration with an ultrasonic bone curette for lumbar
      foraminal stenosis.
AB  - BACKGROUND: Misdiagnosis and inadequate treatment of lumbar foraminal stenosis
      (LFS) are the most common causes of failed back surgery. Although several
      surgical procedures have been reported, the optimal surgical treatment remains
      controversial. AIM: We describe our method of microsurgical medial fenestration
      using an ultrasonic bone curette (Sonopet, Stryker Corp., Kalamazoo, MI, USA) to
      treat patients with LFS and report our early results. PATIENTS AND METHODS: We
      followed up 26 patients who had undergone microsurgical medial fenestration at
      least 1 year earlier. The patients were 15 men and 11 women with a mean age at
      surgery of 59.5 years; the mean follow-up period was 30.6 months. The affected
      nerve root was at L4 in 1 patient and at L5 in 25. Evaluation of our clinical
      results was based on the Japanese Orthopedic Association score. RESULTS: There
      were no intraoperative surgery-related complications. After surgery, 1 patient
      had recurrence of L5 radiculopathy associated with iatrogenic spondylolysis. He
      was successfully treated with resection of the inferior articular process without
      fusion surgery; there was loss of disc height without obvious instability at the
      corresponding level. The Japanese Orthopedic Association scores showed
      significant improvement at 1 month after surgery and at final follow-up
      (p<0.001). No patient had spinal instability or malalignment postoperatively.
      CONCLUSIONS: Microsurgical medial fenestration using Sonopet, a less-invasive
      surgical technique that does not result in spinal instability or malalignment,
      yielded excellent clinical outcomes.

PMID- 23123389
TI  - Dynamic morphologic change and differentiation from fetal to mature pancreatic
      acinar cells in rats.
AB  - BACKGROUND/AIMS: Because of the notion that pancreatic and duodenal homeobox 1
      (PdX-1)-positive cells are pancreatic stem cells that contribute to the
      differentiation and proliferation of exocrine cells, we examined PdX-1-associated
      changes in the morphology of rat pancreatic acinar cells that occur between the
      late fetal and early neonatal periods. METHODS: Light and electron microscopy and
      PdX-1 and MIB-5 immunohistochemistry were used to examine pancreatic tissues
      obtained from fetal rats 22 days postconception (dpc), from newborn rats 48 and
      72 hours after natural birth, and from rats 7 days after natural birth. RESULTS:
      At 22 dpc, the cytoplasm of the acinar cells was large and eosinophilic due to
      accumulation of dense and numerous zymogen granules. Zymogen granules, rough
      endoplasmic reticulum, and other organelles were distributed throughout the
      cytoplasm. At 48 hours, i.e., just after feeding, the cytoplasm appeared smaller,
      less eosinophilic, and vacuolated. Electron microscopic examination showed
      cleaved nuclei and fewer zymogen granules. Expression of both PdX-1 and MIB-5 was
      increased at 48 hours. At 72 hours, acinar cell cytoplasm was decreased in size.
      At 7 days, the acinar cells were larger, biphasic distribution of zymogen
      granules was seen on the eosinophilic apical side, and rough endoplasmic
      reticulum and other ergastoplasms were seen on the basophilic basal side, typical
      of mature pancreatic acinar cells. Expression of PdX-1 and MIB-5 was markedly
      decreased in acinar cells. CONCLUSION: Our findings indicate dynamic PdX-1
      associated morphologic change from fetal to mature pancreatic acinar cells
      between 48 and 72 hours after birth.

PMID- 23123390
TI  - Epidemiological and clinical aspects of human brucellosis in eastern Anatolia.
AB  - BACKGROUND: We investigated the seroprevalence of human brucellosis and risk
      factors in a village in Eastern Anatolia, Turkey, where a brucellosis outbreak
      among cattle had recently occurred. PATIENTS AND METHODS: All 501 inhabitants
      enrolled were screened with the Rose Bengal Test and were asked to fill out a
      questionnaire to determine the signs and symptoms of brucellosis and the risk
      factors. Patients' laboratory findings and clinical responses were also
      evaluated. RESULTS: The Rose Bengal Test was positive in 44 persons. In
      comparison of age groups, fever (20.2%), arthralgia (19.2%) and weight loss
      (8.4%) were frequently seen in children (p<0.05). Hepatomegaly (17.9%) was also
      prevalent in the age group of 0 to 14 years (p<0.05). The consumption of dairy
      products, a family history of brucellosis, and raising livestock were
      significantly related to seropositivity (p<0.05). Rifampicin plus doxycyline was
      the most common regimen administered in these cases (54.5%) and also had the
      highest relapse rate (p<0.05). CONCLUSION: Brucellosis remains an important
      public-health problem in the rural areas of Turkey. Appropriate public health
      measures and education must be pursued to eradicate human brucellosis.

PMID- 23123391
TI  - Acoustic stimulation promotes DNA fragmentation in the Guinea pig cochlea.
AB  - Apoptosis can be described as programmed cell death. Apoptosis regulates cell
      turnover and is involved in various pathological conditions. The characteristic
      features of apoptosis are shrinkage of the cell body, chromatin condensation, and
      nucleic acid fragmentation. During apoptosis, double-stranded DNA is broken down
      into single-stranded DNA (ssDNA) by proteases. Acoustic trauma is commonly
      encountered in otorhinolaryngology clinics. Intense noise can cause inner ear
      damage, such as hearing disturbance, tinnitus, ear fullness, and decreased speech
      discrimination. In this study, we used immunohistochemical and
      electrophysiological methods to examine the fragmentation of DNA in the cochleas
      of guinea pigs that had been exposed to intense noise. Twenty-four guinea pigs
      weighing 250 to 350 g were used. The animals were divided into 4 groups: (I) a
      control group (n=6), (II) a group that was exposed to noise for 2 hours (n=6),
      (III) a group that was exposed to noise for 5 hours (n=6), and (IV) a group that
      was exposed to noise for 20 hours. The stimulus was a pure tone delivered at a
      frequency of 2 kHz. The sound pressure level was 120 dBSPL. No threshold shifts
      were apparent in group I. Group II showed a significant elevation of the hearing
      threshold (ANOVA, p<0.05(*)). The ABR threshold level was also significantly
      elevated immediately after the acoustic stimulation in groups III and IV (ANOVA,
      p<0.01(**)). In groups I, II, and IV, the lateral wall of the ear did not show
      immunoreactivity to ssDNA but did in group III. No immunoreactivity was apparent
      in the organ of Corti in group I or II. However, the supporting cells and outer
      hair cells in groups III and IV showed reactions for ssDNA. The fine structure of
      the organ of Corti had been destroyed in group IV. The lateral wall showed
      immunoreactivity for ssDNA only in group III, whereas the organ of Corti showed
      reactions for ssDNA in groups III and IV. Our study suggests that apoptotic
      changes occur in patients that suffer acoustic trauma. Once the apoptotic pathway
      has started, it is irreversible. Thus, early diagnosis and treatment are
      necessary. Earplugs should also be worn at rock concerts.

PMID- 23123392
TI  - History and current practice of blood purification therapy in nippon medical
      school musashi kosugi hospital: 31 years of practice.
AB  - INTRODUCTION: Renal replacement therapy was established in Japan approximately 40
      years ago, and a blood purification unit was established in our hospital 31 years
      ago. With an eye toward the future, we reviewed and analyzed the practice of
      blood purification therapy in our hospital to date. METHODS: Patients were
      selected from 3 decades when therapy was performed: from October 1979 through
      December 1989, from January 1990 through December 1999, and from January 2000
      through December 2010. RESULTS: The total number of patients was 1,115. The
      numbers of patients with stage 5D/T chronic kidney disease, with acute kidney
      injury, and undergoing therapeutic apheresis has increased with each decade.
      Diabetic nephropathy, chronic glomerulonephritis, and nephrosclerosis are the
      most frequent primary causes of stage 5D/T chronic kidney disease. The percentage
      of patients with diabetic nephropathy at our hospital has increased markedly and
      has recently been more than 50% and has exceeded the national average. The trends
      observed in our study for mean age at the start of dialysis therapy were similar
      to national trends. Peritoneal dialysis was started in 1999, and the percent of
      patients undergoing peritoneal dialysis greatly exceeded the national average.
      Various pathophysiologies were found to be associated with acute kidney injury
      and therapeutic apheresis. CONCLUSION: The number of patients requiring renal
      replacement therapy continues to increase with the development of the hospital,
      especially in the Department of Nephrology. Progress in blood purification
      therapies is remarkable as well. To successfully address these challenges, we
      must strive for continued self-assessment.

PMID- 23123393
TI  - Trial of labor after cesarean delivery as an independent risk factor for
      intrapartum asphyxia in singleton deliveries beyond 37 weeks' gestation.
AB  - The aim of this study was to determine the factors associated with intrapartum
      asphyxia in singleton deliveries beyond 37 weeks' gestation. We reviewed the
      obstetric records of Japanese singleton deliveries after 37 weeks' gestation
      managed at Japanese Red Cross Katsushika Maternity Hospital from 2005 through
      2010. Forty-nine cases were diagnosed as intrapartum asphyxia on the basis of an
      Apgar score <4 at 5 minutes or umbilical arterial pH <7.0 or both. Cases with
      umbilical arterial pH >=7.1 and 1-minute Apgar score >=7 were examined as
      controls (n=10,484). Logistic multivariate regression analysis showed that
      intrapartum asphyxia was independently associated with cases of trial of labor
      after cesarean delivery (adjusted odds ratio, 3.24; 95% confidence intervals, 1.0
      11; p=0.04). Our findings may be encouraging for the counseling of patients
      regarding a possible attempt at trial of labor after cesarean delivery.

PMID- 23123394
TI  - Case of IgG4-related sclerosing cholangitis with a normal serum IgG4 level:
      report of a case.
AB  - Although hilar cholangioma is the most common cause of stricture of the hilar
      bile duct, several diseases can contribute to stenosis. Here, we report on a
      patient with immunoglobulin (Ig) G4-related sclerosing cholangitis (IgG4-SC) of
      the hilar bile duct arising from obstructive jaundice. The patient had undergone
      laparoscopic cholecystectomy for the removal of gallstones. The differential
      diagnosis for icterus included hilar cholangiocarcinoma, primary sclerosing
      cholangitis, IgG4 sclerosing cholangitis, ischemic bile duct stenosis, a
      complication of cholecystitis, amputation neuroma, and iatrogenic stenosis.
      Numerous examinations were performed, but a definite diagnosis remained elusive.
      Because cholangiocarcinoma could not be ruled out, we proposed surgical
      resection. The patient subsequently underwent extended right liver lobectomy and
      intrahepatic cholangiojejunostomy. Pathological examination revealed numerous
      inflammatory cell infiltrates resembling IgG4-positive antibody plasma cells in
      the stromal layer of the stenotic bile duct walls. Hypertrophy of the nerve fiber
      fascicles was not observed. The serum IgG4 level of the patient was within the
      normal range. Few reports of IgG4-SC with a normal serum IgG4 level have been
      published. When this condition presents as it did in the present case,
      establishing a definite diagnosis can be difficult.

PMID- 23123395
TI  - Solitary fibrous tumor arising from the superior nasal turbinate: a case report.
AB  - Solitary fibrous tumor is a rare neoplasm, which was first described as a primary
      spindle-cell tumor of the pleura, is a type of mesenchymal tumor. Although the
      majority of these tumors originate in the pleura, they can also derive from
      extrapleural sites, such as the liver, lung, abdomen, and extremities. We report
      a rare case of a nasal solitary fibrous tumor that originated from the nasal
      superior turbinate. The tumor, measuring 45 * 25 * 10 mm, was in the right nasal
      cavity. We successfully removed the tumor in one piece through endonasal
      endoscopic surgery. The tumor had spindle-shaped cells within a collagenous
      stroma and was positive for CD34. There has been no evidence of tumor recurrence
      in the 14 months following surgery.

PMID- 23123396
TI  - Surgical management of a deep femoral artery aneurysm.
AB  - Standard surgical methods for managing true aneurysms of the deep femoral artery
      have not been established because these aneurysms are rare. An 85-year-old man,
      who had a ruptured aneurysm of the deep femoral artery, underwent aneurysmectomy
      and distal reconstruction with a contralateral autologous vein graft. Three
      dimensional computed tomography is a valuable diagnostic modality to evaluate
      synchronous aneurysms and peripheral arterial circulation for treatment planning.
      Because of their etiology, aneurysms of the deep femoral artery should be treated
      with revascularization when technically feasible, even if the superficial femoral
      artery is patent. A contralateral saphenous vein may be the preferred conduit
      because ipsilateral venous stasis is likely.

PMID- 23123397
TI  - Mediastinal cystic hemangioma presenting as bilateral bloody pleural effusion: a
      case report.
AB  - A 58-year-old man was admitted to our hospital because of dyspnea, dysphagia, and
      back pain. A chest roentgenogram showed bilateral pleural effusion. Bloody fluid
      was aspirated via thoracocentesis, but no malignancy was detected on cytological
      examination. Computed tomography revealed a hypodense circular mass approximately
      8 cm in diameter with well-defined margins in the posterior mediastinum.
      Furthermore, T2-weighted magnetic resonance imaging showed the lesion to be a
      hyperintense mass. Video-assisted thoracoscopic surgery was performed, and the
      tumor was diagnosed as a mediastinal cystic hemangioma. The bilateral bloody
      pleural effusion was attributed to the cystic tumor.

PMID- 23123398
TI  - Dedifferentiated liposarcoma arising from the mesocolon ascendens: report of a
      case.
AB  - Dedifferentiated liposarcoma of the mesentery is an extremely rare tumor. A 71
      year-old man with a 2-month history of abdominal distention was admitted to our
      department for evaluation and treatment of an abdominal mass. Computed tomography
      and magnetic resonance imaging revealed an 11 * 9 cm mass lesion with fat density
      in the upper right abdominal cavity, displacing the ascending and transverse
      colon ventrally. Abdominal angiography showed small feeding vessels of the tumor
      from the ileocolic artery and the middle colic artery. On basis of these
      findings, liposarcoma arising from the mesocolon ascendens was diagnosed, and
      complete removal of the tumor and central pancreatectomy (partial resection of
      the body of the pancreas) were performed. The histopathological diagnosis was
      dedifferentiated liposarcoma, and the patient is free from recurrence 6 months
      after surgery. The treatment strategy for abdominal dedifferentiated liposarcoma
      is surgical resection with a wide surgical margin.

PMID- 23123399
TI  - Oxidative stress and tardive dyskinesia: pharmacogenetic evidence.
AB  - Tardive dyskinesia (TD) is a serious adverse effect of long-term antipsychotic
      use. Because of genetic susceptibility for developing TD and because it is
      difficult to predict and prevent its development prior to or during the early
      stages of medication, pharmacogenetic research of TD is important. Additionally,
      these studies enhance our knowledge of the genetic mechanisms underlying abnormal
      dyskinetic movements, such as Parkinson's disease. However, the pathophysiology
      of TD remains unclear. The oxidative stress hypothesis of TD is one of the
      possible pathophysiologic models for TD. Preclinical and clinical studies of the
      oxidative stress hypothesis of TD indicate that neurotoxic free radical
      production is likely a consequence of antipsychotic medication and is related to
      the occurrence of TD. Several studies on TD have focused on examining the genes
      involved in oxidative stress. Among them, manganese superoxide dismutase gene Ala
      9Val polymorphisms show a relatively consistent association with TD
      susceptibility, although not all studies support this. Numerous pharmacogenetic
      studies have found a positive relationship between TD and oxidative stress based
      on genes involved in the antioxidant defense mechanism, dopamine turnover and
      metabolism, and other antioxidants such as estrogen and melatonin. However, many
      of the positive findings have not been replicated. We expect that more research
      will be needed to address these issues. 

PMID- 23123400
TI  - Context-dependent regulation of Wnt signaling through the primary cilium.
AB  - The primary cilium is a highly conserved environmental sensor and modulator of
      fluid movement in tubular structures. The growing recognition of mutations among
      its many components has led to the discovery of new disorders collectively called
      ciliopathies. Ciliary dysfunction disturbs a variety of signaling pathways along
      its basal body and axoneme that are critical for embryonic development and cell
      and organ homeostasis. Among the many pathways, here we discuss the emerging role
      of Wnt proteins in morphogenic signaling and ciliary biology during health and
      disease.

PMID- 23123401
TI  - Recurrent membranous nephropathy in an allograft caused by IgG3kappa targeting
      the PLA2 receptor.
AB  - Up to 80% of patients with idiopathic membranous nephropathy have non-complement
      fixing IgG4 autoantibodies to the phospholipase A2 receptor (PLA2R). Membranous
      nephropathy recurs in approximately 40% of patients after kidney transplantation,
      but the mechanism is unknown. Here, we describe a patient with recurrent
      membranous nephropathy 13 days after kidney transplantation whose graft biopsy
      specimen showed granular staining for C3, C5b-9, C1q, and IgG3kappa; electron
      microscopy revealed subepithelial nonorganized deposits. A search for hematologic
      disorders was negative. Retrospective evaluation of a biopsy sample from the
      native kidney revealed a similar pattern: monotypic IgG3kappa deposits together
      with C3, C1q, and C5b-9. Glomerular deposits contained PLA2R in both the graft
      and the native kidney, suggesting that the recurrence was the result of
      circulating anti-PLA2R antibodies binding to PLA2R antigen expressed on donor
      podocytes. Confocal analysis of anti-PLA2R and antihuman IgG3 showed co
      localization, and the patient had IgG3kappa-restricted circulating anti-PLA2R
      antibodies. Treatment with rituximab stabilized both proteinuria and serum
      creatinine, and circulating anti-PLA2R became undetectable. In summary, this case
      of recurrent membranous nephropathy in a graft suggests that circulating
      monoclonal anti-PLA2R IgG3kappa caused the disease and activated complement by
      the classic pathway.

PMID- 23123402
TI  - Cell biology of ureter development.
AB  - The mammalian ureter contains two main cell types: a multilayered water-tight
      epithelium called the urothelium, surrounded by smooth muscle layers that, by
      generating proximal to distal peristaltic waves, pump urine from the renal pelvis
      toward the urinary bladder. Here, we review the cellular mechanisms involved in
      the development of these tissues, and the molecules that control the process. We
      consider the relevance of these biologic findings for understanding the
      pathogenesis of human ureter malformations.

PMID- 23123403
TI  - Vitamin D receptor signaling in podocytes protects against diabetic nephropathy.
AB  - Vitamin D and its analogs have antiproteinuric activity and podocytes express the
      vitamin D receptor, but whether vitamin D signaling in podocytes accounts for
      this renoprotection is unknown. To investigate this question, we used the 2.5 kb
      podocin promoter to target Flag-tagged human vitamin D receptor (hVDR) to
      podocytes in DBA/2J mice. After the induction of diabetes with streptozotocin,
      transgenic mice had less albuminuria than wild-type controls. In transgenic mice,
      a low dose of the vitamin D analog doxercalciferol prevented albuminuria,
      markedly attenuated podocyte loss and apoptosis, and reduced glomerular fibrosis,
      but it had little effect on the progression of diabetic nephropathy in wild-type
      mice. Moreover, reconstitution of VDR-null mice with the hVDR transgene in
      podocytes rescued VDR-null mice from severe diabetes-related renal damage. In
      culture, 1,25-dihydroxyvitamin D suppressed high-glucose-induced apoptosis of
      podocytes by blocking p38- and ERK-mediated proapoptotic pathways. Taken
      together, these data provide strong evidence that vitamin D/VDR signaling in
      podocytes plays a critical role in the protection of the kidney from diabetic
      injury.

PMID- 23123404
TI  - Identification and analysis of the human hyaluronan synthase 1 gene promoter
      reveals Smad3- and Sp3-mediated transcriptional induction.
AB  - The ubiquitous mammalian extracellular matrix glycosaminoglycan hyaluronan (HA)
      plays a pivotal role in the regulation of cell phenotype in fibrosis and
      scarring. Transforming growth factor-beta 1 (TGF-beta1) and interleukin-1 beta
      (IL-1beta) up-regulate hyaluronan synthase (HAS) 1 and HAS2 in dermal fibroblasts
      and renal proximal tubular epithelial cells, and subsequent HA synthesis
      regulates cell phenotype. In the present study, we investigated the mechanism of
      HAS1 transcriptional up-regulation in response to these cytokines. We used 5'
      rapid amplification of cDNA ends analysis to identify the 5' end of HAS1
      transcripts, resulting in an increase of 26 nucleotides to the HAS1 exon 1
      sequence of reference sequence NM_001523. Constitutive luciferase activity of
      upstream DNA sequences was shown in luciferase reporter assays, but our reporter
      vector signals were refractory to the addition of TGF-beta1 and IL-1beta. Using
      siRNAs to knockdown transcription factor mRNAs, we showed that TGF-beta1 up
      regulation of HAS1 transcription was mediated via Smad3 but not Smad2, while HAS1
      induction by IL-1?beta was Sp3, not Sp1, dependent.

PMID- 23123406
TI  - Prefrontal activity in Huntington's disease reflects cognitive and
      neuropsychiatric disturbances: the IMAGE-HD study.
AB  - Functional integrity of prefrontal cortico-striatal circuits underlying executive
      functioning may be compromised by basal ganglia degeneration during Huntington's
      disease (HD). This study investigated challenged inhibitory attentional control
      with a shifting response-set (SRS) task whilst assessing neural response via
      functional magnetic resonance imaging (fMRI) in 35 healthy controls, 35 matched
      pre-symptomatic (pre-HD) and 30 symptomatic (symp-HD) participants. A >=70%
      performance accuracy threshold allowed confident identification of neural
      activity associated with SRS performance in a sub-set of 33 healthy controls, 32
      pre-HD and 20 symp-HD participants. SRS activated dorsolateral prefrontal and
      dorsal anterior cingulate cortices, premotor, parietal, and basal ganglia regions
      and deactivated subgenual anterior cingulate cortex. Symp-HD participants showed
      greater prefrontal functional responses relative to controls and pre-HD,
      including larger activations and larger deactivations in response to cognitive
      challenge, consistent with compensatory neural recruitment. We then investigated
      associations between prefrontal BOLD responses, SRS performance accuracy and
      neuropsychiatric disturbance in all participants, including those below SRS
      performance accuracy threshold. We observed that reduced prefrontal responsivity
      in symp-HD was associated with reduced accuracy in SRS performance, and with
      increased neuropsychiatric disturbance within domains including executive
      dysfunction, pathological impulses, disinhibition, and depression. These findings
      demonstrate prefrontal response during inhibitory attentional control usefully
      characterises cognitive and neuropsychiatric status in symp-HD. The functional
      integrity of compensatory prefrontal responses may provide a useful marker for
      treatments which aim to sustain cognitive function and delay executive and
      neuropsychiatric disturbance.

PMID- 23123405
TI  - Fiber tract stimulation can reduce epileptiform activity in an in-vitro bilateral
      hippocampal slice preparation.
AB  - Mesial temporal lobe epilepsy (MTLE) is a common medically refractory
      neurological disease that has been treated with electrical stimulation of gray
      matter with limited success. However, stimulation of a white matter tract
      connecting the hippocampi could maximize treatment efficacy and extent. We tested
      low-frequency stimulation (LFS) of a novel target that enables simultaneous
      targeting of bilateral hippocampi: the ventral hippocampal commissure (VHC) with
      a novel in-vitro slice preparation containing bilateral hippocampi connected by
      the VHC. The goal of this study is to understand the role of hippocampal
      interplay in seizure propagation and reduction by commissural fiber tract
      stimulation. LFS is applied to the VHC as extracellular and intracellular
      recording techniques are combined with signal processing to estimate several
      metrics of epilepsy including: (1) total time occupied by seizure activity (%);
      (2) seizure duration (s); (3) seizures per minute (#); and (4) power in the ictal
      (V(2)Hz(-1)); as well as (5) interictal spectra (V(2)Hz(-1)). Bilateral
      epileptiform activity in this preparation is highly correlated between
      hippocampi. Application of LFS to the VHC reduces all metrics of epilepsy during
      treatment in an amplitude and frequency dependent manner. This study lends
      several insights into the mechanisms of bilateral seizure reduction by LFS of the
      VHC, including that depolarization blocking, LTD/LTP and GABA(A) are not
      involved. Importantly, enhanced post-stimulation 1-Hz spiking correlates with
      long-lasting seizure reduction and both are heightened by targeting bilateral
      hippocampi via the VHC. Therefore, stimulating bilateral hippocampi via a single
      electrode in the VHC may provide an effective MTLE treatment.

PMID- 23123408
TI  - Review: Endocrine disrupting chemicals and immune responses: a focus on bisphenol
      A and its potential mechanisms.
AB  - Endocrine disrupting chemicals (EDCs) have become of concern for a variety f
      health issues. Due to their effects on the endocrine system they have been
      thoroughly examined with regards to sexual dysfunction, malformation, and cancers
      of reproductive origin. Bisphenol-A (BPA) is a widely studied EDC and has been
      characterized regarding its estrogenic effects on a variety of cell types. BPA
      also alters immune responses. In this review, we examine some of the documented
      effects of EDCs, with a focus on BPA that pertain to modulation of the immune
      system and various immune cell populations. We highlight the multiple actions of
      BPA on altering T cell subsets, B cell functions, and dendritic cell and
      macrophage biology. Finally, we consider that these immunological activities of
      BPA may be mediated through estrogen receptor signaling, arylhydrocarbon
      receptor, and the peroxisome proliferator-activated receptor family of nuclear
      receptors.

PMID- 23123409
TI  - Mutations analysis of C1 inhibitor coding sequence gene among Portuguese patients
      with hereditary angioedema.
AB  - Mutations that modify the amino acid sequence of C1-INH (except Val458Met) are
      associated with HAE. More than 200 different mutations scattering the entire C1
      INH gene have been reported. The main objective of this study was to report the
      mutational findings in a HAE cohort of 138 Portuguese patients followed in
      specialized consultation all over the country. DNA was extracted from peripheral
      blood with QiaSymphony BioRobot (QIAGEN Portugal). The sequence reactions were
      performed by using a DNA sequencing kit (Big Dye terminator cycle sequencing
      v1.1/v3.1 from Applied Biosystems) and sequencing products were immediately
      submitted to direct sequencing on an Applied Biosystem 3130 DNA Analyser. DNA
      sequences were analyzed at four different stages. Raw data and sequence
      alignments of all 8 exons and intron-exon boundaries were performed for each
      patient individually with SeqScape software and using SERPING1 gene NG_009625 of
      24,300 bp (12-March-2011) as reference sequence. Sequence comparisons among
      patients and controls were performed with software CodonCode Aligner v.3.7 from
      CodonCode Corp and with Geneious 4.5 from Biomatters Lda. A total of 94 point
      mutations were observed among patients, and 67% of them were located on exon 8.
      In addition, we noticed one not described stop codon at position c.1459 C>T in
      three different patients. Translation termination was also found on exon 3 and 7,
      as a result of mutations at positions c.481A>7, c.1174C>T. In this population,
      the prevalence of the missense mutation p.Arg444Cys was 39 out of 42. Mutational
      analysis revealed 22 different pathogenic mutations, of which 64% were not
      described on HAE database. Although identification of disease causing mutations
      is not necessary to establish HAE diagnosis, studies on gene expression and
      characterization of rearrangements in SERPING1 gene are suggested in order to get
      new insights on function and genetic tests of C1 inhibitor.

PMID- 23123407
TI  - Inhibition of the Jak-STAT pathway prevents CNTF-mediated survival of axotomized
      oxytocinergic magnocellular neurons in organotypic cultures of the rat supraoptic
      nucleus.
AB  - Previous studies have demonstrated that ciliary neurotrophic factor (CNTF)
      enhances survival and process outgrowth from magnocellular neurons in the
      paraventricular (PVN) and the supraoptic (SON) nuclei. However, the mechanisms by
      which CNTF facilitates these processes remain to be determined. Therefore, the
      aim of this study was to identify the immediate signal transduction events that
      occur within the rat SON following administration of exogenous rat recombinant
      CNTF (rrCNTF) and to determine the contribution of those intracellular signaling
      pathway(s) to neuronal survival and process outgrowth, respectively.
      Immunohistochemical and Western blot analyses demonstrated that axonal injury and
      acute unilateral pressure injection of 100 ng/MUl of rrCNTF directly over the rat
      SON resulted in a rapid and transient increase in phosphorylated-STAT3 (pSTAT3)
      in astrocytes but not neurons in the SON in vivo. Utilizing rat hypothalamic
      organotypic explant cultures, we then demonstrated that administration of 25
      ng/ml rrCNTF for 14days significantly increased the survival and process
      outgrowth of OT magnocellular neurons. In addition, pharmacological inhibition of
      the Jak-STAT pathway via AG490 and cucurbitacin I significantly reduced the
      survival of OT magnocellular neurons in the SON and PVN; however, the
      contribution of the Jak-STAT pathway to CNTF-mediated process outgrowth remains
      to be determined. Together, these data indicate that CNTF-induced survival of OT
      magnocellular neurons is mediated indirectly through astrocytes via the Jak-STAT
      signaling pathway.

PMID- 23123411
TI  - Membrane association of peroxiredoxin-2 in red cells is mediated by the N
      terminal cytoplasmic domain of band 3.
AB  - Band 3 (B3), the anion transporter, is an integral membrane protein that plays a
      key structural role by anchoring the plasma membrane to the spectrin-based
      membrane skeleton in the red cell. In addition, it also plays a critical role in
      the assembly of glycolytic enzymes to regulate red cell metabolism. However, its
      ability to recruit proteins that can prevent membrane oxidation has not been
      previously explored. In this study, using a variety of experimental approaches
      including cross-linking studies, fluorescence and dichroic measurements, surface
      plasmon resonance analysis, and proteolytic digestion assays, we document that
      the antioxidant protein peroxiredoxin-2 (PRDX2), the third most abundant
      cytoplasmic protein in RBCs, interacts with the cytoplasmic domain of B3. The
      surface electrostatic potential analysis and stoichiometry measurements revealed
      that the N-terminal peptide of B3 is involved in the interaction. PRDX2 underwent
      a conformational change upon its binding to B3 without losing its peroxidase
      activity. Hemichrome formation induced by phenylhydrazine of RBCs prevented
      membrane association of PRDX2, implying overlapping binding sites. Documentation
      of the absence of binding of PRDX2 to B3 Neapolis red cell membranes, in which
      the initial N-terminal 11 amino acids are deleted, enabled us to conclude that
      PRDX2 binds to the N-terminal cytoplasmic domain of B3 and that the first 11
      amino acids of this domain are crucial for PRDX2 membrane association in intact
      RBCs. These findings imply yet another important role for B3 in regulating red
      cell membrane function.

PMID- 23123412
TI  - Cocaethylene as a biomarker to predict heavy alcohol exposure among cocaine
      users.
AB  - BACKGROUND: Cocaethylene (CE) is a cocaine metabolite formed during alcohol and
      cocaine co-consumption. There are no previous studies to assess the effectiveness
      of hair CE as a biomarker indicating chronic alcohol consumption among
      individuals who have consumed cocaine. OBJECTIVES: To establish the ability of CE
      to predict chronic alcohol use among individuals testing positive for cocaine.
      METHODS: We studied all cases referred to our laboratory where both chronic
      cocaine and alcohol consumption were sought, and values of hair cocaine,
      benzoylegconine (BE), CE, and FAEEs (as marker of chronic alcohol consumption )
      were available. Cocaine, BE and CE were screened by ELISA and confirmed using
      headspace-solid phase microextraction (HS-SPME) and GC-MS. FAEE were analyzed
      using HS-SPME and GC-MS/EI. Sensitivity, specificity, and predictive values of CE
      as a marker of alcohol consumption among cocaine users were calculated using
      different FAEE cutoffs. RESULTS: Cocaine (P<0.001) and BE (P<0.001)
      concentrations were associated with increased FAEE. The positive predictive value
      of CE to identify alcohol consumption was 0.66 for excessive drinking and 0.76
      for chronic drinking among positive cocaine users. Negative CE ruled out almost
      completely excessive alcohol consumption. CONCLUSION: Positive hair CE results
      had high specificity for chronic excessive alcohol consumption among cocaine
      users. With no established safe level of alcohol in pregnancy, identification of
      CE in hair of pregnant women who have used cocaine can serve as a biomarker for
      fetal alcohol spectrum disorder.

PMID- 23123410
TI  - Glutathiolated Ras: characterization and implications for Ras activation.
AB  - Ras GTPases cycle between active GTP-bound and inactive GDP-bound forms to
      regulate a multitude of cellular processes, including cell growth,
      differentiation, and apoptosis. The activation state of Ras is regulated by
      protein modulatory agents that accelerate the slow intrinsic rates of GDP
      dissociation and GTP hydrolysis. Similar to the action of guanine-nucleotide
      exchange factors, the rate of GDP dissociation can be greatly enhanced by the
      reaction of Ras with small-molecule redox agents, such as nitrogen dioxide, which
      can promote Ras activation. Nitrogen dioxide is an autoxidation product of nitric
      oxide and can react with an accessible cysteine of Ras to cause oxidation of the
      bound guanine nucleotide to facilitate Ras guanine nucleotide dissociation.
      Glutathione has also been reported to modify Ras and alter its activity. To
      elucidate the mechanism by which glutathione alters Ras guanine nucleotide
      binding properties, we performed NMR, top-down and bottom-up mass spectrometry,
      and biochemical analyses of glutathiolated Ras. We determined that treatment of H
      Ras, lacking the nonconserved hypervariable region, with oxidized glutathione
      results in glutathiolation specifically at cysteine 118. However, glutathiolation
      does not alter Ras structure or biochemical properties. Rather, changes in
      guanine nucleotide binding properties and Ras activity occur upon exposure of Ras
      to free radicals, presumably through the generation of a cysteine 118 thiyl
      radical. Interestingly, Ras glutathiolation protects Ras from further free
      radical-mediated activation events. Therefore, glutathiolation does not affect
      Ras activity unless Ras is modified by glutathione through a radical-mediated
      mechanism.

PMID- 23123414
TI  - A primary arterial-ureteral fistula after an aortic-bifemoral bypass.
AB  - INTRODUCTION: Primary arterial-ureteral fistula is a rare and diagnostically
      challenging condition which may present with massive hematuria. PRESENTATION OF
      CASE: A case of primary arterial-ureteral fistula (AUF) is presented in a patient
      with a previous prosthetic aortic-bifemoral bypass. The AUF treated with arterial
      and ureteral resection, arterial ligation and ureteral reconstruction.
      DISCUSSION: Primary AUF are more frequently associated with aneurysmal
      degeneration of the arterial wall. The development of a primary fistula due to an
      iliac artery aneurysm many years after an aortic-bifemoral bypass performed due
      to atherosclerotic obstructive disease is a very unusual presentation of this
      entity. Multiple surgical strategies can be employed in achieving hemorrhage and
      infection control, urinary tract continuity, and vascular reconstruction.
      CONCLUSION: A multidisciplinary approach and the achievement of a pre-operative
      diagnosis are essential for an effective management of this condition with
      prognostic implications.

PMID- 23123413
TI  - Isolated primary squamous cell carcinoma of the tympanic membrane.
AB  - INTRODUCTION: Primary squamous cell carcinoma (SCC) of the tympanic membrane is
      exceptionally rare. We describe the history, investigation and management of this
      disease. PRESENTATION OF CASE: A 68-year-old woman presented with a three month
      history of intermittent otorrhoea and external ear canal (EAC) pruritus. Otoscopy
      revealed a polypoidal granular nodule, confined to the posterior aspect of the
      tympanic membrane. Examination under anaesthesia (EUA) confirmed that the lesion
      was confined to the tympanic membrane, with a surrounding rim of normal drum.
      Biopsies were consistent with well differentiated SCC. DISCUSSION: Following
      discussion at multi-disciplinary team meeting for treatment planning, the patient
      underwent lateral temporal bone resection with ipsilateral superficial
      parotidectomy and selective neck dissection. Post-operative histology confirmed
      an SCC confined to the tympanic membrane. CONCLUSION: SCC of the tympanic
      membrane is an extremely rare condition. As with early temporal bone SCC,
      surgical resection with adjacent structure clearance remains the primary
      treatment modality.

PMID- 23123415
TI  - Large liposarcoma developing in the ischiorectal fossa: Report of a rare case.
AB  - INTRODUCTION: We herein report an extremely rare case of a liposarcoma developing
      in the ischiorectal fossa that was completely resected using a transsacral
      approach. PRESENTATION OF CASE: A 74-year-old man was admitted to our institute
      because of a large perianal tumor. A pelvic magnetic resonance imaging (MRI)
      revealed an 8cm*7cm*5cm sized encapsulated heterogeneous tumor on the right side
      of the ischiorectal fossa. Transsacral excision was performed under a diagnosis
      of liposarcoma. The tumor was partially fixed to the external sphincter and
      puborectalis. Therefore, the muscles were partially resected to ensure sufficient
      margins. Histopathological examination revealed a well differentiated liposarcoma
      and negative surgical margins. DISCUSSION: The basic treatment strategy of
      liposarcoma is surgical resection, whereas the effects of chemotherapy or
      radiotherapy remain limited. Although no postoperative adjuvant therapy has been
      performed in our case, no recurrences have occurred for 1 year after surgery.
      CONCLUSION: Although the curative resection of large tumors located in the
      ischiorectal fossa is usually difficult, the complete resection of liposarcoma is
      the main potentially curative treatment. A transsacral approach is useful for a
      complete resection.

PMID- 23123416
TI  - Giant atrial thrombus presenting as a tumor.
AB  - INTRODUCTION: Right Atrial masses may represent tumors or thrombi of the heart
      and are potentially fatal if left untreated. PRESENTATION OF CASE: A 45-year-old
      woman with a previous history of breast cancer who was found to have a right
      atrial mass diagnosed as a tumor by Echocardiography and Computed Tomography
      which ultimately proved to be a giant organized thrombus at surgery. DISCUSSION:
      Metastatic tumors of the heart are 20 times more common than primary tumors and
      malignancies that often involve the heart include breast, lung, lymphoma,
      melanoma and sarcomas. Myxomas remain the most common cause of atrial tumors and
      are classically described arising on the left but a significant amount do occur
      on the right side. Presenting features with masses in the right atrium are
      similar to patients with tricuspid stenosis which may present with tiredeness,
      swelling of the feet, hepatomegaly and ascites. The clinical presentation and
      history may be of help in the diagnosis especially if the patient has a confirmed
      tumour. CONCLUSION: Despite our current state of the art equipment these "masses"
      still pose a diagnostic challenge in distinguishing between solid thrombus and
      tumour as to determine the appropriate therapeutic approach. Surgical removal of
      Giant Atrial Thrombi appears to be the procedure of Choice.

PMID- 23123417
TI  - Recurrent benign schwannoma of the scalp: Case report.
AB  - INTRODUCTION: Schwannomas are benign neoplasm's arising from Schwann cells.
      Malignant change is rare. PRESENTATION OF CASE: A 42-yearold man presented with a
      6-year history of a recurrent right sided multinodular scalp lesion. DISCUSSION:
      Surgery revealed multiple ovoid masses in a scalp lesion. Histology revealed
      benign schwannoma. CONCLUSION: Schwannoma may present as multiple lesions in a
      multilobulated scalp lesion and should be considered as differential diagnosis.

PMID- 23123418
TI  - Pancreatic GIST with pancreas divisum: A new entity.
AB  - INTRODUCTION: Gastrointestinal stromal tumours (GISTs) are uncommon intra
      abdominal tumours. These tumours tend to arise with a higher frequency in the
      stomach and the small bowel. In fewer than 5% of cases, they originate primarily
      from extra-gastrointestinal tumours (EGISTs). Gastrointestinal stromal tumour of
      the pancreas is very rare. Only few cases have been published. We report the
      first case of stromal tumour of the pancreas with concomitant pancreas divisum.
      PRESENTATION OF CASE: A 39-year-old male who presented with constipation and
      abdominal pain. A computerized tomography demonstrated a 9cm pancreatic mass,
      without liver lesions. A Whipple procedure with segmental colectomy was performed
      with success. After 24months follow up, the patient is doing well and disease
      free. DISCUSSION: Mesenchymal tumours of the pancreas are extremely rare,
      accounting for less than 1% of all pancreatic tumours. The endoscopic ultrasound
      is helpful for diagnosis. Surgical resection with negative pathologic margins
      remains the treatment of choice. CONCLUSION: in our knowledge, this is the first
      case of pancreatic GIST with pancreas divisum. Although pancreatic GISTs are
      uncommon tumours, they must be considered in the differential diagnosis of solid
      pancreatic lesions. Even though the tumour can be evaluated as high risk,
      treatment must be aggressive in order to improve survival rate.

PMID- 23123420
TI  - Metastatic hepatocellular carcinoma to the parotid gland: Case report and review
      of the literature.
AB  - INTRODUCTION: Hepatocellular carcinoma, the most frequent primary hepatic tumor,
      metastasizes in more than 50% of cases. However, parotid gland metastatic HCCs
      are very uncommon. We report a patient in whom the finding of a left parotid mass
      revealed metastatic HCC. PRESENTATION OF CASE: A thirty-six-year-old male
      presented with a round palpable left neck mass that persisted for 3 months. He
      had received right hemihepatectomy for hepatocellular carcinoma (HCC).
      Preoperative evaluation revealed a benign tumor of the parotid gland. We
      performed superficial parotidectomy. Metastatic hepatocellular carcinoma of the
      parotid gland was diagnosed. DISCUSSION: Although HCC metastases to the oral
      cavity have been reported, to date, only 4 cases HCC metastasis to the parotid
      gland have been reported. Although clinicians and cytopathologists alike both
      agree that salivary gland fine needle aspiration biopies (FNABs) are highly
      useful and safe diagnostic alternatives to biopsies and resections, we believe
      that in specific clinical situations, awareness of potential diagnostic pitfalls
      in salivary gland FNAB is a necessary part of the microscopic interpretations of
      these lesions. CONCLUSION: Although rare, since HCC can metastasize to the
      parotid gland, high suspicion should be maintained in a patient presenting with a
      parotid mass with a history of HCC. In addition, since potential diagnostic
      pitfalls in salivary gland fine-needle aspiration (FNA) biopsies exist,
      incisional or excisional biopsy may be necessary for definite diagnosis of
      metastatic HCC to the parotid gland.

PMID- 23123419
TI  - A rare presentation of midgut malrotation as an acute intestinal obstruction in
      an adult: Two case reports and literature review.
AB  - INTRODUCTION: Midgut malrotation is a congenital anomaly presenting mainly in the
      childhood. Its presentation as an acute intestinal obstruction is extremely rare
      in adults usually recognized intra-operatively, therefore a high index of
      suspicion is always required when dealing with any case of acute intestinal
      obstruction. PRESENTATION OF CASE: We report two cases of young adults who
      presented with symptoms of acute intestinal obstruction and were diagnosed intra
      operatively as cecal volvulus and paraduodenal hernia, respectively, caused by
      midgut malrotation. Post-operative CT scan confirmed these findings. DISCUSSION:
      Malrotation of the intestinal tract is a product of an aberrant embryology. The
      presentation of intestinal malrotation in adults is rare (0.2-0.5%). Contrast
      enhanced CT can show the abnormal anatomic location of a right sided small bowel,
      a left-sided colon and an abnormal relationship of the superior mesenteric vein
      (SMV) situated to the left of the superior mesenteric artery (SMA) instead of to
      the right. CONCLUSION: Anomalies like midgut malrotation can present as an
      operative surprise and awareness regarding these anomalies can help surgeons deal
      with these conditions.

PMID- 23123421
TI  - Sequential robotic-assisted bladder diverticulectomy and radical prostatectomy.
      Technique and review of the literature.
AB  - INTRODUCTION: Acquired bladder diverticula (BD) in men over the age of 60 are
      usually due to bladder outlet obstruction (BOO) secondary to prostatic
      enlargement. In cases of clinical significant BD with persistent symptoms or
      complications surgical excision should be considered. In the treatment of BD it
      is important to address the BOO with a bladder outlet procedure either
      simultaneously or in a staged fashion. PRESENTATION OF CASE: We present to the
      best of our knowledge, the first case of sequential robotic-assisted bladder
      diverticulectomy (RABD) combined with robotic-assisted radical prostatectomy
      (RARP) in a patient with large diverticula and malignant prostate enlargement as
      the cause of BOO. DISCUSSION: Concomitant open radical prostatectomy and bladder
      diverticulectomy series have been described, while minimal invasive procedures
      combining BD excision with relive of BOO especially due to benign prostatic
      enlargement have been reported to be safe and effective. CONCLUSION: Concomitant
      RABD with RARP is a safe and effective procedure with excellent oncological and
      functional results.

PMID- 23123422
TI  - Melanin biosynthesis pathway in Agaricus bisporus mushrooms.
AB  - With the full genome sequence of Agaricus bisporus available, it was possible to
      investigate the genes involved in the melanin biosynthesis pathway of button
      mushrooms. Based on different BLAST and alignments, genes were identified in the
      genome which are postulated to be involved in this pathway. Seven housekeeping
      genes were tested of which 18S rRNA was the only housekeeping gene that was
      stably expressed in various tissues of different developmental stages. Gene
      expression was determined for most gene homologs (26 genes) involved in the
      melanin pathway. Of the analysed genes, those encoding polyphenol oxidase (PPO),
      the PPO co-factor L-chain (unique for A. bisporus), and a putative transcription
      factor (photoregulator B) were among the highest expressed in skin tissue. An in
      depth look was taken at the clustering of several PPO genes and the PPO co-factor
      gene on chromosome 5, which showed that almost 25% of the protein encoding genes
      in this cluster have a conserved NACHT and WD40 domain or a P-loop nucleoside
      triphosphate hydrolase. This article will be the start for an in depth study of
      the melanin pathway and its role in quality losses of this economically important
      product.

PMID- 23123423
TI  - Two-component signal transduction in Agaricus bisporus: a comparative genomic
      analysis with other basidiomycetes through the web-based tool BASID2CS.
AB  - Two-component systems (TCSs) are signal transduction mechanisms present in many
      eukaryotes, including fungi that play essential roles in the regulation of
      several cellular functions and responses. In this study, we carry out a genomic
      analysis of the TCS proteins in two varieties of the white button mushroom
      Agaricus bisporus. The genomes of both A. bisporus varieties contain eight genes
      coding for TCS proteins, which include four hybrid Histidine Kinases (HKs), a
      single histidine-containing phosphotransfer (HPt) protein and three Response
      Regulators (RRs). Comparison of the TCS proteins among A. bisporus and the
      sequenced basidiomycetes showed a conserved core complement of five TCS proteins
      including the Tco1/Nik1 hybrid HK, HPt protein and Ssk1, Skn7 and Rim15-like RRs.
      In addition, Dual-HKs, unusual hybrid HKs with 2 HK and 2 RR domains, are absent
      in A. bisporus and are limited to various species of basidiomycetes. Differential
      expression analysis showed no significant up- or down-regulation of the Agaricus
      TCS genes in the conditions/tissue analyzed with the exception of the Skn7-like
      RR gene (Agabi_varbisH97_2|198669) that is significantly up-regulated on compost
      compared to cultured mycelia. Furthermore, the pipeline web server BASID2CS
      (http://bioinformatics.unavarra.es:1000/B2CS/BASID2CS.htm) has been specifically
      designed for the identification, classification and functional annotation of
      putative TCS proteins from any predicted proteome of basidiomycetes using a
      combination of several bioinformatic approaches.

PMID- 23123424
TI  - Critical appraisal of the assessment of benefits and risks for foods, 'BRAFO
      Consensus Working Group'.
AB  - BRAFO, Benefit-Risk Analysis for Foods, was a European Commission project funded
      within Framework Six as a Specific Support Action and coordinated by ILSI Europe.
      BRAFO developed a tiered methodology for assessing the benefits and risks of
      foods and food components, utilising a quantitative, common scale for health
      assessment in higher tiers. This manuscript reports on the implications of the
      experience gained during the development of the project for the further
      improvement of benefit-risk assessment methodology. It was concluded that the
      methodology proposed is applicable to a range of situations and that it does help
      in optimising resource utilisation through early identification of those benefit
      risk questions where benefit clearly outweighs risk or vice versa. However,
      higher tier assessments are complex and demanding of time and resources,
      emphasising the need for prioritisation. Areas identified as requiring further
      development to improve the utility of benefit-risk assessment include health
      weights for different populations and endpoints where they do not currently
      exist, extrapolation of effects from studies in animals to humans, use of in
      vitro data in benefit-risk assessments, and biomarkers of early effect and how
      these would be used in a quantitative assessment.

PMID- 23123425
TI  - Dietary quercetin ameliorates nonalcoholic steatohepatitis induced by a high-fat
      diet in gerbils.
AB  - Dietary quercetin is highly abundant in edible plants, which possesses a wide
      range of pharmacological properties. This study was to investigate
      hepatoprotective effects of quercetin in the nonalcoholic steatohepatitis (NASH)
      gerbils induced by a high-fat diet (HFD), and to evaluate its regulatory
      mechanism on hepatic inflammatory response. The gerbils were fed with HFD for 28
      days to induce NASH. From 15th day to 28th day, the treated drugs were given
      daily to each animal, respectively. The lipid profiles and biochemical markers
      were determined at the end of the experiment. The expressions of Sirt1, NF-kappaB
      p65 and iNOS were detected by immunohistochemistry and Western blot analysis. The
      results showed that oral administration of quercetin at doses of 30-60 mg/kg to
      hyperlipidemia rats for 14 days were highly effective in decreasing the levels of
      serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein
      cholesterol (LDL-C), alanine aminotransferase (ALT) and aspartate
      aminotransferase (AST). It could decrease lipid accumulation in the hepatocytes,
      and reduce serum levels of pro-inflammatory cytokines TNF-alpha and IL-6 via
      regulating the expressions of Sirt1, NF-kappaB p65 and iNOS. Thus, dietary
      quercetin had significant therapeutic benefits and could be explored as a
      potential promising candidate for the prevention of NASH.

PMID- 23123426
TI  - Miniaturization of hydrolase assays in thermocyclers.
AB  - We adapted the protocols of reducing sugar measurements with dinitrosalicylic
      acid and bicinchoninic acid for thermocyclers and their use in enzymatic assays
      for hydrolases such as amylase and beta-1,3-glucanase. The use of thermocyclers
      for these enzymatic assays resulted in a 10 times reduction in the amount of
      reagent and volume of the sample needed when compared with conventional
      microplate protocols. We standardized absorbance readings from the polymerase
      chain reaction plates, which allowed us to make direct readings of the techniques
      above, and a beta-glycosidase assay was also established under the same
      conditions. Standardization of the enzymatic reaction in thermocyclers resulted
      in less time-consuming temperature calibrations and without loss of volume
      through leakage or evaporation from the microplate. Kinetic parameters were
      successfully obtained, and the use of the thermocycler allowed the measurement of
      enzymatic activities in biological samples from the field with a limited amount
      of protein.

PMID- 23123427
TI  - Simple and inexpensive three-step rapid amplification of cDNA 5' ends using 5'
      phosphorylated primers.
AB  - Rapid amplification of cDNA 5' ends (5'-RACE) is routinely used for the sequence
      analysis of the upstream noncoding regions of cellular mRNAs; however, it
      represents a tedious and cost-intensive procedure. By employing 5' phosphorylated
      gene-specific primers for first-strand cDNA synthesis, we cut short the
      previously established reverse ligation and amplification protocol of Mandl and
      coworkers (BioTechniques, 1991, vol. 10, pp. 484-486) to a streamlined three-step
      procedure that no longer depends on enzymatic mRNA decapping or linker ligation.
      The novel three-step protocol has been validated by mapping the transcriptional
      start sites of heterologously expressed yellow fever virus genomic RNAs from
      cultured mammalian cells.

PMID- 23123428
TI  - Mechanism of action of 4-dialkylaminopyridines as secondary enhancers in enhanced
      chemiluminescence reaction.
AB  - Kinetic study of peroxidase-catalyzed oxidation of 3-(10'-phenothiazinyl)propane
      1-sulfonate (SPTZ) by hydrogen peroxide demonstrated that the addition of 4
      dialkylaminopyridines to a substrate solution significantly increased a rate of
      production of SPTZ cation radical and did not affect the rate of decomposition of
      this radical. These results explain the mechanism of action of 4
      dialkylaminopyridines as secondary enhancers in enhanced chemiluminescence
      reaction used widely in analytical practice.

PMID- 23123430
TI  - High-density lipoproteins inhibit vascular endothelial inflammation by increasing
      3beta-hydroxysteroid-Delta24 reductase expression and inducing heme oxygenase-1.
AB  - RATIONALE: Lipid-free apolipoprotein (apo) A-I and discoidal reconstituted high
      density lipoproteins (rHDL) containing apoA-I, (A-I)rHDL, inhibit vascular
      inflammation by increasing 3beta-hydroxysteroid-Delta24 reductase (DHCR24)
      expression. OBJECTIVE: To determine whether the lipid-free apoA-I-mediated and (A
      I)rHDL-mediated increase in DHCR24 expression induces the cytoprotective and
      potentially cardioprotective enzyme, heme oxygenase-1 (HO-1). METHODS AND
      RESULTS: In vivo: A single intravenous infusion of lipid-free apoA-I (8 mg/kg)
      administered 24 hours before inserting a nonocclusive periarterial carotid collar
      into New Zealand White rabbits decreased collar-induced endothelial vascular cell
      adhesion molecule-1 and intercellular adhesion molecule-1 expression, reduced
      intima/media neutrophil infiltration, and increased DHCR24 and HO-1 mRNA levels.
      Knockdown of vascular DHCR24 and HO-1 and systemic administration of tin
      protoporphyrin-IX, an HO inhibitor, abolished these anti-inflammatory effects. In
      vitro: Preincubation of human coronary artery endothelial cells with (A-I)rHDL
      before activation with tumor necrosis factor-alpha increased DHCR24 and HO-1 mRNA
      levels and inhibited cytokine-induced vascular cell adhesion molecule-1 and
      intercellular adhesion molecule-1 expression. Transfection of the cells with
      DHCR24 and HO-1 small interfering RNA and tin-protoporphyrin-IX treatment
      abolished these effects. The (A-I)rHDL-mediated induction of HO-1 was reduced in
      human coronary artery endothelial cells transfected with DHCR24 small interfering
      RNA. Transfection of human coronary artery endothelial cells with HO-1 small
      interfering RNA and tin-protoporphyrin-IX treatment did not inhibit the (A-I)rHDL
      mediated increase in DHCR24 expression. Inhibition of phosphatidylinositol 3
      kinase/Akt reduced the (A-I)rHDL-mediated increase in HO-1, but not DHCR24
      expression. The activation of phosphatidylinositol 3-kinase/Akt by (A-I)rHDL was
      decreased in human coronary artery endothelial cells that were transfected with
      DHCR24 small interfering RNA. CONCLUSIONS: Lipid-free apoA-I and (A-I)rHDL
      inhibit inflammation by increasing DHCR24 expression, which, in turn, activates
      phosphatidylinositol 3-kinase/Akt and induces HO-1.

PMID- 23123431
TI  - Does a more "physiological" infant manikin design effect chest compression
      quality and create a potential for thoracic over-compression during simulated
      infant CPR?
AB  - Poor survivability following infant cardiac arrest has been attributed to poor
      quality chest compressions. Current infant CPR manikins, used to teach and revise
      chest compression technique, appear to limit maximum compression depths (CDmax)
      to 40 mm. This study evaluates the effect of a more "physiological" CDmax on
      chest compression quality and assesses whether proposed injury risk thresholds
      are exceeded by thoracic over-compression. A commercially available infant CPR
      manikin was instrumented to record chest compressions and modified to enable
      compression depths of 40 mm (original; CDmax40) and 56 mm (the internal thoracic
      depth of a three-month-old male infant; CDmax56). Forty certified European
      Paediatric Life Support instructors performed two-thumb (TT) and two-finger (TF)
      chest compressions at both CDmax settings in a randomised crossover sequence.
      Chest compression performance was compared to recommended targets and compression
      depths were compared to a proposed thoracic over-compression threshold.
      Compressions achieved greater depths across both techniques using the CDmax56,
      with 44% of TT and 34% of TF chest compressions achieving the recommended
      targets. Compressions achieved depths that exceeded the proposed intra-thoracic
      injury threshold. The modified manikin (CDmax56) improved duty cycle compliance;
      however, the chest compression rate was consistently too high. Overall, the
      quality of chest compressions remained poor in comparison with internationally
      recommended guidelines. This data indicates that the use of a modified manikin
      (CDmax56) as a training aid may encourage resuscitators to habitually perform
      deeper chest compressions, whilst avoiding thoracic over-compression and thereby
      improving current CPR quality. Future work will evaluate resuscitator performance
      within a more realistic, simulated CPR environment.

PMID- 23123429
TI  - Identification of ADP-ribosylation sites of CD38 mutants by precursor ion
      scanning mass spectrometry.
AB  - Protein ADP-ribosylation, including mono- and poly-ADP-ribosylation, is
      increasingly recognized to play important roles in various biological pathways.
      Molecular understanding of the functions of ADP-ribosylation requires the
      identification of the sites of modification. Although tandem mass spectrometry
      (MS/MS) is widely recognized as an effective means for determining protein
      modifications, identification of ADP-ribosylation sites has been challenging due
      to the labile and hydrophilic nature of the modification. Here we applied
      precursor ion scanning-triggered MS/MS analysis on a hybrid quadrupole linear ion
      trap mass spectrometer for selectively detecting ADP-ribosylated peptides and
      determining the auto-ADP-ribosylation sites of CD38 (cluster of differentiation
      38) E226D and E226Q mutants. CD38 is an enzyme that catalyzes the hydrolysis of
      nicotinamide adenine dinucleotide (NAD) to ADP-ribose. Here we show that NAD can
      covalently label CD38 E226D and E226Q mutants but not wild-type CD38. In this
      study, we have successfully identified the D226/Q226 and K129 residues of the two
      CD38 mutants being the ADP-ribosylation sites using precursor ion scanning hybrid
      quadrupole linear ion trap mass spectrometry. The results offer insights about
      the CD38 enzymatic reaction mechanism. The precursor ion scanning method should
      be useful for identifying the modification sites of other ADP-ribosyltransferases
      such as poly(ADP-ribose) polymerases.

PMID- 23123432
TI  - Assessment of corneal endothelial cell density in patients with keratoconus not
      using contact lenses.
AB  - PURPOSE: To assess the corneal endothelial cell density (ECD) in keratoconus
      patients with no history of contact lens use. SETTING: Yuzuncu Yil University,
      School of Medicine and Van Training and Research Hospital, Department of
      Ophthalmology, Van, Turkey. DESIGN: Cross-sectional controlled study. METHODS:
      The eyes of 65 patients with the diagnosis of keratoconus with no history of
      contact lens wear and the eyes of 40 healthy controls were prospectively examined
      using the Heidelberg Retinal Tomography Rostock Cornea Module (HRT3/RCM). The
      average ECD from the two groups were then compared. RESULTS: Of the cases with
      keratoconus, 44 (67.7%) were men and 21 (32.3%) were women. The mean age was
      20.9+/-6.8 (range=10-41) years. Of the controls, 28 (70%) were men and 12 (30%)
      were women. The mean age was 23.9+/-5.8 (range=14-35) years. Of the 65 eyes with
      keratoconus, 19 (29.2%) had mild keratoconus, 21 (32.3%) had moderate
      keratoconus, and 25 (38.5%) had severe keratoconus. The mean ECD was 2731.6+/
      303.2 cells/mm2 in cases with keratoconus and 2664.9+/-319.5 cells/mm2 in
      controls. There was no difference between the densities (unpaired t-test, P=0.4).
      No significant relationships were found between the ECD data and central corneal
      thickness or steepest keratometric. CONCLUSIONS: Endothelial cell density was
      unaltered in keratoconic patients without a history of contact lens use when
      compared with healthy controls. Change in ECD is independent from the central
      corneal thickness and the stage of keratoconus.

PMID- 23123433
TI  - Polymicrobial and microsporidial keratitis in a patient using Boston scleral
      contact lens for Sjogren's syndrome and ocular cicatricial pemphigoid.
AB  - AIM: To report a rare case of microsporidial and polymicrobial keratitis in a
      patient with Sjogren's syndrome and ocular cicatricial pemphigoid. METHOD: This
      is a descriptive case report. A 66-year-old lady diagnosed with Sjogren's
      syndrome (SS) and ocular cicatricial pemphigoid (OCP) presented to us with
      microbial keratitis after using a Boston sclera contact lens for a painful
      epithelial defect. After 9 days of medical treatment, she underwent therapeutic
      penetrating keratoplasty. RESULTS: 10% potassium hydroxide and calcofluor white
      wet mount revealed microsporidial spores. Gram positive cocci and Gram variable
      bacilli on Gram stain were identified as Staphylococcus epidermidis and
      Corynebacterium accolens in culture. Histopathological examination of the corneal
      tissue confirmed the presence of microsporidial spores. CONCLUSION: Microsporidal
      keratitis can occur in patients with severe ocular surface disease due to SS and
      OCP. Predisposing factors include dry eye, local and systemic immunosuppression
      and Boston scleral contact lens. Early surgical intervention may be needed to
      eradicate the infection.

PMID- 23123434
TI  - Keratoconus presenting with bilateral simultaneous acute corneal hydrops.
AB  - PURPOSE: To report a case of unknown keratoconus presenting with bilateral
      simultaneous acute corneal hydrops. METHODS: Case report. RESULTS: A case of a 12
      year-old male patient with Leber congenital amaurosis (LCA) presented with sudden
      whitening and lacrimation for 2 days in both eyes simultaneously. At the initial
      examination, there were bilateral acute corneal hydrops, enophthalmic eyes and
      roving nystagmus. Ultrasonography revealed clear crystalline lenses and attached
      retina. Initial management consisted of topical hypertonic solutions, steroids
      and artificial tears. CONCLUSION: Bilateral simultaneous acute corneal hydrops
      has not been reported before in the literature. It may be the presenting sign of
      keratoconus.

PMID- 23123435
TI  - Plasmon excitation in electron energy-loss spectroscopy for determination of
      indium concentration in (In,Ga)N/GaN nanowires.
AB  - We demonstrate the potential of low-loss electron energy-loss spectroscopy in
      transmission electron microscopy as a quick and straightforward method to
      determine the local indium compositions in (In,Ga)N/GaN nanowires. The
      (In,Ga)N/GaN nanowire heterostructures are grown by plasma assisted molecular
      beam epitaxy on Si(111) substrates in a self-assembled way, and on patterned GaN
      templates in an ordered way. A wide range of indium contents is realized by
      varying the substrate temperatures. The plasmon peak in low-loss electron energy
      loss spectroscopy exhibits a linear relation with respect to indium concentration
      in (In,Ga)N nanowires, allowing for a direct compositional analysis. The high
      spatial resolution of this method in combination with structural information from
      transmission electron microscopy will contribute to a basic understanding of the
      lattice pulling effect during (In,Ga)N/GaN nanowire growth.

PMID- 23123436
TI  - Patient preferences for technical skills versus interpersonal skills in
      chiropractors and physiotherapists treating low back pain.
AB  - BACKGROUND: Little is known about which characteristics of chiropractors and
      physiotherapists matter to patients and influence their preferences when seeking
      care. OBJECTIVE: To examine the impact of four factors (patient gender,
      practitioner gender, practitioner specialty-chiropractor or physiotherapist and
      practitioner reputation-technical ability or interpersonal skills) on patients'
      choice of therapist to treat low back pain. METHODS: Questionnaire-based vignette
      study in which participants sampled from the general population rated the
      likelihood of consulting eight fictional therapists. Each fictional therapist
      represented a different combination of the three practitioner factors (e.g. male
      chiropractor with reputation for good technical ability). The study was
      administered as a postal survey to a simple random sample of residences in one
      postal town in England. RESULTS: Respondents (n = 657) consistently reported that
      they considered a practitioner's qualifications and technical skills important
      when choosing either a physiotherapist or a chiropractor; and just less than a
      third thought it was important that a practitioner was a good listener. As
      hypothesized, female respondents preferred female practitioners and respondents
      had a general preference for physiotherapists over chiropractors. Contrary to our
      hypothesis, the practitioner's reputation had the largest effect on respondents'
      preferences and all practitioners with a reputation for technical ability were
      preferred over those with a reputation for interpersonal skills. CONCLUSION:
      Similar factors are important to patients whether they are choosing an individual
      chiropractor or physiotherapist; patients particularly value information about
      technical competence. An awareness of these factors should help primary care
      providers to direct patients to relevant information and support their decision
      making.

PMID- 23123438
TI  - Effect of electrical stimulation on botulinum toxin a therapy in patients with
      chronic myofascial pain syndrome: a 16-week randomized double-blinded study.
AB  - OBJECTIVE: To evaluate the effect of different intensities of electrical
      stimulation on botulinum toxin A (BTX-A) injection at trigger points (TrPs) in
      patients with chronic myofascial pain syndrome (MPS). DESIGN: Double-blind
      randomized trial. SETTING: Outpatient rehabilitation clinic. PARTICIPANTS:
      Patients (N=76) with chronic MPS of the neck and shoulder regions. INTERVENTIONS:
      Patients were randomly assigned to 1 of 2 intervention groups: BTX-A injection
      followed by (1) electrical stimulation that induces visible muscle contraction
      (MOTOR group); or (2) electrical stimulation with an intensity just above the
      sensory threshold (SENSORY group). Electrical stimulation was administered for 30
      minutes a day for 3 consecutive days after injection. MAIN OUTCOME MEASURES: The
      primary outcome was the visual analog scale (VAS) for pain. Secondary outcomes
      included the Neck Pain and Disability Scale (NPAD), Global Assessment of
      Improvement Scale (GAS), and pressure pain threshold (PPT). RESULTS: The VAS
      scores decreased significantly at 4, 8, 12, and 16 weeks from the baseline in
      both groups. Significant changes in the NPAD score over time were noted only in
      the SENSORY group at 8, 12, and 16 weeks. The SENSORY group showed lower VAS and
      NPAD scores at 16 weeks (P=.043 and P=.041, respectively), and higher treatment
      success rates at 12 and 16 weeks (P=.039 and P=.024, respectively) than the MOTOR
      group. There was no significant result in the GAS and PPT. CONCLUSIONS: Short
      term electrical stimulation may affect the reduction in pain after BTX-A
      injection at TrPs in patients with chronic MPS of the neck and shoulder regions.
      Based on the results, it seems that sensory electrical stimulation was superior
      to motor electrical stimulation as an adjuvant therapy to BTX-A injection in
      patients with chronic MPS. Further studies are warranted to investigate the
      method facilitating the effect of BTX-A on MPS.

PMID- 23123437
TI  - Innate immune tolerance and the role of kupffer cells in differential responses
      to interferon therapy among patients with HCV genotype 1 infection.
AB  - BACKGROUND & AIMS: In patients with hepatitis C virus (HCV) infection, interferon
      alfa (IFN-alpha) alters expression of IFN-stimulated genes (ISGs), but little is
      understood about factors that determine outcomes of therapy. We used a systems
      biology approach to evaluate the acute response of patients with chronic
      hepatitis C to IFN-alpha therapy. METHODS: We collected liver biopsy samples from
      8 treatment-naive patients with chronic HCV genotype 1 infection at baseline and
      24 hours after treatment with IFN-alpha-2a (10 MU subcutaneously). Blood samples
      were collected before and up to 48 hours after administration of IFN-alpha-2a to
      measure HCV RNA levels and for gene expression analysis. Patients then received
      pegylated IFN-alpha-2a and ribavirin on day 5 of the study; therapy continued for
      up to 48 weeks. RESULTS: Based on the kinetics of HCV RNA during the first 12
      weeks of therapy, 2 patients were rapid virologic responders, 4 were early
      virologic responders, and 2 did not respond to therapy (nonresponders).
      Nonresponders had high pretreatment levels of ISG expression in the liver but not
      in peripheral blood mononuclear cells. In responders, after administration of IFN
      alpha, intrahepatic ISG expression increased significantly from baseline and was
      associated with a rapid phase 1 decrease in HCV. We identified distinct hepatic
      expression and tissue distribution patterns of ISGs that segregated with
      treatment outcome. Importantly, Kupffer cells were a local source of IFN that
      promoted basal expression of ISG in hepatocytes of nonresponders. This finding
      was validated in cultured THP1 human macrophages that expressed IFN-beta after
      exposure to viable HCV 2a. When Huh7 K2040 and Huh7 L2198S hepatoma cells were
      incubated with IFN-alpha-2a, expression of ISGs peaked by 4 hours and decreased
      by 72 hours, associated with an increase in level of HCV RNA. This indicates that
      constitutive exposure to IFN causes hepatoma cells to become tolerant of ISG
      function. CONCLUSIONS: In patients with chronic HCV infection, IFN production by
      Kupffer cells might promote innate immune tolerance, characterized by a lack of
      response to IFN therapy. Strategies to disrupt the virus-host interactions that
      induce innate immune tolerance should improve therapy.

PMID- 23123439
TI  - Left-sided brain injury associated with more hospital-acquired infections during
      inpatient rehabilitation.
AB  - OBJECTIVE: To test the hypothesis that a left-dominant brain immune network (LD
      BIN) might affect the occurrence of infection during inpatient rehabilitation of
      stroke and traumatic brain injury (TBI). DESIGN: A retrospective analysis was
      performed on electronic medical records between January 2009 and December 2010.
      All patients with left- or right-sided stroke or TBI were included into the
      study. The LD-BIN hypothesis was tested by comparing HAI rates depending on
      whether patients had left- or right-sided brain lesions. SETTING: A large
      inpatient rehabilitation hospital. PARTICIPANTS: Among the patients (N=2236) with
      stroke or TBI who had either a left- or right-sided brain lesion, 163 patients
      were identified with HAIs. INTERVENTION: Not applicable. MAIN OUTCOME MEASURE:
      Frequency of HAIs. RESULTS: In the 163 patients identified with HAIs with a
      diagnosis of stroke or TBI, chi-square analysis revealed a significantly higher
      proportion of HAIs among patients with left-sided (n=98; 60.1%) relative to right
      sided (n=65; 39.9%) brain injuries (chi(2)=6.68, P<.01). These effects could not
      be attributed to either clinical or demographic factors. CONCLUSIONS: Our
      findings are consistent with the hypothesis that an LD-BIN may mediate
      vulnerability to infection during rehabilitation of patients with stroke or TBI.
      Further translational research investigating novel means of managing patients
      based on brain lesion location, and modulating the LD-BIN via behavioral and
      physiologic interventions, may result in neuroscience-based methods to improve
      infection resistance in brain-injured patients.

PMID- 23123440
TI  - Novel autoantibodies in Sjogren's syndrome.
AB  - Sjogren's syndrome (SS) is defined by autoantibodies to Ro and La. The current
      studies identified additional autoantibodies in SS to salivary gland protein 1
      (SP-1), carbonic anhydrase 6 (CA6) and parotid secretory protein (PSP). These
      autoantibodies were present in two animal models for SS and occurred earlier in
      the course of the disease than antibodies to Ro or La. Patients with SS also
      produced antibodies to SP-1, CA6 and PSP. These antibodies were found in 45% of
      patients meeting the criteria for SS who lacked antibodies to Ro or La.
      Furthermore, in patients with idiopathic xerostomia and xerophthalmia for less
      than 2 years, 76% had antibodies to SP-1 and/or CA6 while only 31% had antibodies
      to Ro or La. Antibodies to SP-1, CA6 and PSP may be useful markers for
      identifying patients with SS at early stages of the disease or those that lack
      antibodies to either Ro or La.

PMID- 23123441
TI  - Effects of Rehmannia glutinosa oligosaccharide on human adipose-derived
      mesenchymal stem cells in vitro.
AB  - AIMS: Adipose-derived mesenchymal stem cells (ADMSCs) are considered as a good
      cell source for regenerative medicine with their self-renew capacity,
      multilineage differentiation and immunomodulatory potency. Based on this
      background, the aim of this study was to evaluate the influence of Rehmannia
      glutinosa oligosaccharide (RGO), a traditional Chinese medicine, on human ADMSCs'
      proliferation, H(2)O(2)-induced apoptosis, and secretion of Vascular endothelial
      growth factor (VEGF) and hepatocyte growth factor (HGF) in vitro. MAIN METHODS:
      Human ADMSCs were isolated and cultured in vitro. Then flow cytometry was carried
      out to characterize the cells, and MTT assay was performed to detect the
      proliferation. H(2)O(2)-induced apoptosis was evaluated by flow cytometry. VEGF
      and HGF production were detected by ELISA kits. KEY FINDINGS: Human ADMSCs were
      positive for CD90 and CD29, but negative for CD31, CD34 and CD45. The results
      also indicate that RGO can promote the proliferation and alleviate H(2)O(2)
      induced apoptosis of human ADMSCs. The mechanism of RGO's protective effect may
      involve the up-regulation of VEGF and HGF. SIGNIFICANCE: The present study
      indicates that RGO may increase the viability and proliferative capacity and
      alleviate H(2)O(2)-induced apoptosis of human ADMSCs via the paracrine release of
      VEGF and HGF. These results indicate that RGO application will enhance stem cell
      viability and improve their effects in cell therapy.

PMID- 23123442
TI  - Protective effects of agmatine on lipopolysaccharide-injured microglia and
      inducible nitric oxide synthase activity.
AB  - AIMS: Proinflammatory factors released from activated microglia contribute to
      maintaining homeostasis against various noxious stimuli in the central nervous
      system. If excessive, however, they may initiate a pathologic neuroinflammatory
      process. In this investigation, we evaluated whether agmatine, a primary
      polyamine known to protect neurons, reduces lipopolysaccharide (LPS)-induced
      damage to microglia in vitro and in vivo. MAIN METHODS: For in vitro study, BV2
      immortalized murine microglia were exposed to LPS with agmatine treatment. After
      24hours, cell viability and the amount of nitrite generated were determined. For
      in vivo study, LPS was microinjected into the corpus callosum of adult male
      albino mice. Agmatine was intraperitoneally administered at the time of injury.
      Brains were evaluated 24hours after LPS microinjection to check for
      immunoreactivity with a microglial marker of ionized calcium binding adaptor
      molecule 1 (Iba1) and inducible nitric oxide synthase (iNOS). Using western blot
      analysis, protein expression of iNOS as well as that of the proinflammatory
      cytokines, tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta, was
      determined. KEY FINDINGS: Agmatine significantly reduced the LPS-induced BV2
      microglial cytotoxicity from over 80% to less than 60% (p<0.001), as determined
      by lactate dehydrogenase assay. It suppressed the nitrite production from 16.4+/
      3.14MUM to 5.5+/-1.27MUM (p<0.001), as measured using the Griess reaction.
      Agmatine also decreased the activities of microglia and iNOS induced by LPS
      microinjection into corpus callosum. SIGNIFICANCE: Our findings reveal that
      agmatine attenuates LPS-induced microglial damage and suggest that agmatine may
      serve as a novel therapeutic strategy for neuroinflammatory diseases.

PMID- 23123445
TI  - Chromaffin cell transplants: from the lab to the clinic.
AB  - Chromaffin cell transplants have been explored since the early 1980s as a
      promising alternative in different pathological states, mainly Parkinson's
      disease and chronic pain. Advances are significant since transplants have been
      performed in humans. The general mechanism of these transplants relies in the
      capacity of chromaffin cells to act as mini-pumps that release amines and
      peptides. Different strategies are being used to improve the efficacy of
      transplants. However, a remaining hurdle is to determine the viability across
      time and the interaction with the microenvironment of the graft. We analyzed
      previous and current results finding that although there is a lot of positive
      evidence, there is also a lack of molecular studies that support behavioral
      results. The present review gives an update on recent advances of chromaffin cell
      transplants and their future in the clinic.

PMID- 23123444
TI  - Evaluation of a novel poly N-acetyl glucosamine (pGlcNAc) hydrogel for treatment
      of the degenerating intervertebral disc.
AB  - AIMS: The early stages of degenerative disc disease (DDD) primarily affect the
      disc nucleus pulposus (NP). Tissue-engineered strategies may enhance
      intervertebral disc (IVD) functionality. The aim of this study was to develop and
      evaluate a novel deacetylated poly-N-acetyl glucosamine (pGlcNAc) hydrogel
      characterizing its biochemical effect on human IVD cells as well as material
      biomechanical properties. MAIN METHODS: A novel deacetylated derivative of a
      marine diatom-derived glycosaminoglycan was developed into a hydrogel formulation
      as a potential therapy to treat degenerating IVD NP. In vitro biochemical studies
      were conducted using primary human disc cell cultures to evaluate cell viability,
      metabolic activity, proteoglycan and extracellular matrix protein expression. The
      biomechanical hydration kinetics and viscoelastic behavior of the hydrogel were
      determined and compared with the behavior of human lumbar NP. KEY FINDINGS: Disc
      cell viability, metabolic activity, and proteoglycan content of the treated cells
      were observed to be significantly greater in experimental samples when compared
      to untreated control groups. RT-PCR and immunohistochemical data corroborated the
      expression of characteristic NP disc markers, aggrecan and type II collagen in
      cultured cells. Rheological data demonstrated that the elastic component of the
      hydrogel dominated the viscous component over a frequency range of 0.1 to
      15.85rad/s. Of several formulations evaluated, a sulphated, deactylated
      derivative of the nanofiber derived pGlcNAc hydrogel demonstrated the most robust
      biologic effects on cell viability, metabolic activity, and proteoglycan
      expression. SIGNIFICANCE: This in vitro study using human disc cells demonstrates
      that a sulphated deacetylated glycosaminoglycan derivative hydrogel possesses
      promising characteristics motivating further evaluation as a potential therapy
      for NP degeneration.

PMID- 23123446
TI  - Probable involvement of Ca(2+)-activated Cl(-) channels (CaCCs) in the activation
      of CB1 cannabinoid receptors.
AB  - AIMS: Recently, we demonstrated that peripheral antinociception induced by delta
      opioid receptor is dependent of Ca(2+)-activated Cl(-) channels (CaCCs). Because
      opioid and cannabinoid receptors share some common mechanisms of action, our
      objective was to identify a possible relationship between CaCCs and the
      endocannabinoid system. MAIN METHODS: To induce hyperalgesia, rat paws were
      treated with intraplantar prostaglandin E2 (PGE2, 2MUg). Nociceptive thresholds
      to pressure (grams) were measured using an algesimetric apparatus 3h following
      injection. Probabilities were calculated using ANOVA/Bonferroni's test, and
      values that were less than 5% were considered to be statistically significant.
      KEY FINDINGS: Administration of the cannabinoid agonist CB1 anandamide (12.5, 25
      and 50MUg/paw) and the cannabinoid agonist CB2 PEA (5, 10 and 20MUg/paw)
      decreased the PGE2-induced hyperalgesia in a dose-dependent manner. The
      possibility of the higher doses of anandamide (50MUg) and PEA (20MUg) having a
      central or systemic effect was excluded because the administration of the drug
      into the contralateral paw did not elicit antinociception in the right paw. As
      expected, the antinociceptive effects induced by anandamide and PEA were blocked
      by the CB1 and CB2 receptor antagonists AM251 and AM630, respectively. The
      peripheral antinociception was induced by anandamide but not PEA and was dose
      dependently inhibited by the CaCC blocker niflumic acid (8, 16 and 32MUg).
      SIGNIFICANCE: These results provide the first evidence for the involvement of
      CaCCs in the peripheral antinociception induced by activation of the CB1
      cannabinoid receptor.

PMID- 23123448
TI  - Modulation of zymosan-induced peritonitis by riboflavin co-injection, pre
      injection or post-injection in male Swiss mice.
AB  - AIMS: We compared the effects of riboflavin pre-injection, co-injection and post
      injection on several symptoms of zymosan-induced peritonitis in male Swiss mice.
      Additionally, the effects of i.p. injection of riboflavin itself were elucidated.
      MAIN METHODS: Peritonitis was induced in Swiss mice (50 animals) by i.p. zymosan
      (Z; 40mg/kg) injection. Riboflavin (R; 0, 20, 50, or 100mg/kg) was applied either
      alone or in combination with zymosan. In the latter case riboflavin was
      administered either together with zymosan (R group), or 30min before zymosan (R-Z
      group), or 1h later (Z-R group). The nociceptive response was evaluated by
      counting body writhes. The peritoneal exudates retrieved 4h after the R or Z
      injection were analyzed for the numbers and apoptosis of polymorphonuclear
      leukocytes (PMNs), and levels of metalloproteinase 9 (MMP-9), nitric oxide, and
      inflammatory cytokines, IL-12p70, TNFalpha, MCP-1, IL-6, IL-10, IFNgamma. KEY
      FINDINGS: Riboflavin itself induced nociceptive-related body writhes and a
      moderate inflammatory response manifested by PMN influx and the release of some
      cytokines and MMP-9. In contrast, antinociceptive properties of riboflavin were
      significant in the ZR group co-injected with the lowest dose of riboflavin
      (ZR20). At the 4th hour of zymosan-induced peritonitis an intraperitoneal
      accumulation of PMNs was decreased in the riboflavin-treated groups and cytokine
      profiles were modified according to riboflavin dose and the time of injection.
      SIGNIFICANCE: Riboflavin itself induces low-grade nociception and inflammation
      while its effects on zymosan-induced inflammation are dependent on the dose and
      time of its application: either before or during inflammation.

PMID- 23123443
TI  - Diabetic cardiomyopathy and metabolic remodeling of the heart.
AB  - The incidence and prevalence of diabetes mellitus are both increasing rapidly in
      societies around the globe. The majority of patients with diabetes succumb
      ultimately to heart disease, much of which stems from atherosclerotic disease and
      hypertension. However, the diabetic milieu is itself intrinsically noxious to the
      heart, and cardiomyopathy can develop independent of elevated blood pressure or
      coronary artery disease. This process, termed diabetic cardiomyopathy, is
      characterized by significant changes in the physiology, structure, and mechanical
      function of the heart. Presently, therapy for patients with diabetes focuses
      largely on glucose control, and attention to the heart commences with the onset
      of symptoms. When the latter develops, standard therapy for heart failure is
      applied. However, recent studies highlight that specific elements of the
      pathogenesis of diabetic heart disease are unique, raising the prospect of
      diabetes-specific therapeutic intervention. Here, we review recently unveiled
      insights into the pathogenesis of diabetic cardiomyopathy and associated
      metabolic remodeling with an eye toward identifying novel targets with
      therapeutic potential.

PMID- 23123449
TI  - Phenethyl caffeate benzo[kl]xanthene lignan with DNA interacting properties
      induces DNA damage and apoptosis in colon cancer cells.
AB  - AIMS: Phenethyl caffeate benzoxanthene lignan (PCBL) is a synthetic compound with
      DNA interacting, antiangiogenic, antiproliferative and tumor cell death inducing
      abilities. Though PCBL exhibits the qualities of a prospective antitumor agent,
      the basic mechanism of PCBL induced cell death remains unknown. This study aims
      to analyze the molecular mechanisms of PCBL induced cell death in tumor cells to
      further substantiate its antitumor abilities. MAIN METHODS: MTT assay was used
      for finding cell proliferation inhibition, flow cytometric analysis for the
      detection of cell cycle arrest, comet assay for DNA break detection and
      immunofluorescence for analyzing H2AX phosphorylation. Western blot analysis was
      used to detect the activation of different proteins related to DNA damage
      response and apoptosis. KEY FINDINGS: PCBL inhibited proliferation of WiDr cells
      more efficiently than its analog, MCBL. Comet analysis of PCBL treated WiDr cells
      and activity of various DNA damage response proteins such as gamma-H2AX, BRCA1,
      ATR and Chk1 in PCBL treated cells demonstrated the DNA damaging property of
      PCBL. Effector molecules of apoptosis such as caspase-3, caspase-7 and caspase-9
      were found activated along with PARP cleavage in PCBL treated cells, suggesting
      apoptosis as the main mode of cell death. PCBL induced cell death was found
      associated with the activation of MAPK signaling. Inhibition of ERK, one of the
      MAPKs, by U0126 improved the apoptosis inducing ability of PCBL. SIGNIFICANCE: In
      vitro findings suggest that PCBL works by initiating DNA damage and inducing
      apoptosis in cancer cells and thus could be considered for further preclinical
      studies.

PMID- 23123450
TI  - In vivo imaging and quantitative monitoring of autophagic flux in tobacco BY-2
      cells.
AB  - Autophagy has been shown to play essential roles in the growth, development and
      survival of eukaryotic cells. However, simple methods for quantification and
      visualization of autophagic flux remain to be developed in living plant cells.
      Here, we analyzed the autophagic flux in transgenic tobacco BY-2 cell lines
      expressing fluorescence-tagged NtATG8a as a marker for autophagosome formation.
      Under sucrose-starved conditions, the number of punctate signals of YFP-NtATG8a
      increased, and the fluorescence intensity of the cytoplasm and nucleoplasm
      decreased. Conversely, these changes were not observed in BY-2 cells expressing a
      C-terminal glycine deletion mutant of the NtATG8a protein (NtATG8aDeltaG). To
      monitor the autophagic flux more easily, we generated a transgenic BY-2 cell line
      expressing NtATG8a fused to a pH-sensitive fluorescent tag, a tandem fusion of
      the acid-insensitive RFP and the acid-sensitive YFP. In sucrose-rich conditions,
      both fluorescent signals were detected in the cytoplasm and only weakly in the
      vacuole. In contrast, under sucrose-starved conditions, the fluorescence
      intensity of the cytoplasm decreased, and the RFP signal clearly increased in the
      vacuole, corresponding to the fusion of the autophagosome to the vacuole and
      translocation of ATG8 from the cytoplasm to the vacuole. Moreover, we introduce a
      novel simple easy way to monitor the autophagic flux non-invasively by only
      measuring the ratio of fluorescence of RFP and YFP in the cell suspension using a
      fluorescent image analyzer without microscopy. The present in vivo quantitative
      monitoring system for the autophagic flux offers a powerful tool for determining
      the physiological functions and molecular mechanisms of plant autophagy induced
      by environmental stimuli. 

PMID- 23123447
TI  - Roles of alcohol and tobacco exposure in the development of hepatocellular
      carcinoma.
AB  - The purpose of this report is to summarize the roles of alcohol and tobacco
      exposure in the development of hepatocellular carcinoma (HCC). Chronic heavy
      alcohol exposure is a major risk factor for HCC, which is the most frequent type
      of liver cancer. Alcohol ingestion may initiate and or promote the development of
      HCC by: 1) acetaldehyde-DNA adduct formation; 2) cytochrome P4502E1-associated
      reactive oxygen species (ROS) generation , lipid peroxidation, p53 mutation, and
      conversion of pro-carcinogens to carcinogens; 3) iron accumulation that leads to
      ROS generation, lipid peroxidation, p53 mutation, and initiation of inflammatory
      cascade via nuclear factor-KappaB (NF-kB) activation; 4) glutathione depletion
      leading to oxidative stress; 5) s-adenosylmethionine (SAM) depletion and
      associated DNA hypomethylation of oncogenes ; 6) retinoic acid depletion and
      resultant hepatocyte proliferation via up-regulation of activator protein-1 (AP
      1); 7) initiating an inflammatory cascade through increased transfer of endotoxin
      from intestine to liver, Kupffer cell activation via CD14/toll-like receptor-4
      (TLR-4), oxidative stress, NF-kB or early growth response-1(Egr-1) activation,
      and generation of inflammatory cytokines and chemokines; 8) induction of liver
      fibrosis; and 9) decreasing the number and/or function of natural killer cells.
      Tobacco exposure is also a risk factor for HCC. It may contribute to the
      initiation and promotion of HCC due the presence of mutagenic and carcinogenic
      compounds as well as by causing oxidative stress due to generation of ROS and
      depletion of endogenous antioxidants. Simultaneous exposure to alcohol and
      tobacco is expected to promote the development of HCC in an additive and/or
      synergistic manner.

PMID- 23123451
TI  - Cyclophilins: proteins in search of function.
AB  - Cyclophilins constitute a subgroup of large family of proteins called
      immunophilins, which also include FKBPs and Parvulins. They are remarkably
      conserved in all genera, highlighting their pivotal role in important cellular
      processes. Most cyclophilins display PPIase enzymatic activity, multiplicity,
      diverse cellular locations and active role in protein folding which render them
      to be included in the class of diverse set of proteins called molecular
      chaperones. Due to their distinct PPIase function, besides protein disulfide
      isomerases and protein foldases, cyclophilins have been deemed necessary for in
      vivo chaperoning activity. Unlike other cellular chaperones, these proteins are
      specific in their respective targets. Not all cyclophilin proteins possess PPIase
      activity, indicating a loss of their PPIase activity during the course of
      evolution and gain of function independent of their PPIase activity. The PPIase
      function of cyclophilins is also compensated by their functional homologs, like
      FKBPs. Multiple cyclophilin members in plants like Arabidopsis and rice have been
      reported to be associated with diverse functions and regulatory pathways through
      their foldase, scaffolding, chaperoning or other unknown activities. Although
      many functions of plant cyclophilins were reported or suggested, the
      physiological relevance and molecular basis of stress-responsive expression of
      plant cyclophilins is still largely unknown. However, their wide distribution and
      ubiquitous nature signifies their fundamental importance in plant survival.
      Several of these members have also been directly linked to multiple stresses.
      This review attempts to deal with plant cyclophilins with respect to their role
      in stress response. 

PMID- 23123453
TI  - Molecular interaction of bZIP domains of GBF1, HY5 and HYH in Arabidopsis
      seedling development.
AB  - The bZIP proteins, GBF1, HY5 and HYH, play important regulatory roles in
      Arabidopsis seedling development. Whereas GBF1 plays a dual regulatory role, HY5
      and HYH act as positive regulators of photomorphogenesis. The molecular and
      functional relations of GBF1 with HY5 and HYH in photomorphogenesis have recently
      been demonstrated. However, the possible interaction of bZIP domain of each of
      these proteins remains to be investigated. In this study, our results suggest
      that bZIP domains of HY5 and HYH are able to interact with the bZIP domain of
      GBF1. Taken together with the earlier study, (9) these results suggest that the N
      terminal domain of GBF1 has an inhibitory effect on its interaction with HY5 and
      HYH. 

PMID- 23123454
TI  - EcmPred: prediction of extracellular matrix proteins based on random forest with
      maximum relevance minimum redundancy feature selection.
AB  - The extracellular matrix (ECM) is a major component of tissues of multicellular
      organisms. It consists of secreted macromolecules, mainly polysaccharides and
      glycoproteins. Malfunctions of ECM proteins lead to severe disorders such as
      marfan syndrome, osteogenesis imperfecta, numerous chondrodysplasias, and skin
      diseases. In this work, we report a random forest approach, EcmPred, for the
      prediction of ECM proteins from protein sequences. EcmPred was trained on a
      dataset containing 300 ECM and 300 non-ECM and tested on a dataset containing 145
      ECM and 4187 non-ECM proteins. EcmPred achieved 83% accuracy on the training and
      77% on the test dataset. EcmPred predicted 15 out of 20 experimentally verified
      ECM proteins. By scanning the entire human proteome, we predicted novel ECM
      proteins validated with gene ontology and InterPro. The dataset and standalone
      version of the EcmPred software is available at http://www.inb.uni
      luebeck.de/tools-demos/Extracellular_matrix_proteins/EcmPred.

PMID- 23123452
TI  - Cytotoxic isoferulic acidamide from Myricaria germanica (Tamaricaceae).
AB  - Tamgermanitin, a unique N-trans-Isoferuloyltyramine, together with the hitherto
      unknown polyphenolics, 2,4-di-O-galloyl-(alpha/beta)-glucopyranose and
      kaempferide 3,7-disulphate have been isolated from the leaf aqueous ethanol
      extract of the false tamarisk, Myricaria germanica DESV. In addition, 18 known
      phenolics were also separated and characterized. All structures were elucidated
      on the basis of detailed analysis of 1D- (1)H and (13)C NMR, COSY, HSQC, HMBC and
      HRFTESIMS spectral data. The extract, its chromatographic column fractions and
      the isolated isoferuloyltyramine, tamgermanetin demonstrated potential cytotoxic
      effect against three different tumor cell lines, namely liver (Huh-7), breast
      (MCF-7) and prostate (PC-3). The IC 50''s were found to be substantially low with
      low-resistance possibility. DNA flow-cytometic analysis indicated that column
      fractions and tamgermanetin enhanced pre-G apoptotic fraction. Both materials
      showed inhibiting activity against PARP enzyme activity. In conclusion, we report
      the isolation and identification of a novel compound, tamgermanitin, from the
      aqueous ethanol extract of Myricaria germanica leaves. Further, different
      fractions of the extract and tamgermanitin exhibit potent cytotoxic activities
      which warrant further investigations. 

PMID- 23123455
TI  - Nanoparticle-mediated delivery of anticancer agents to tumor angiogenic vessels.
AB  - Nanoparticle-mediated drug delivery systems targeting tumor angiogenic vessels
      have been studied for antineovascular cancer therapy achieved by induction of
      apoptosis of angiogenic endothelial cells. Nanoparticles such as liposomes are
      considered to accumulate in tumors due to the enhanced permeability and retention
      effect. The delivery efficiency of this system appears to be affected by the
      density of tumor angiogenic vessels regardless of modification with tumor
      targeting ligands on the surface of nanoparticles. It remains a challenging
      problem to deliver sufficient amounts of anticancer drugs to hypovascular tumors
      using nanoparticles. On the other hand, the strategy of angiogenic vessel
      targeting is theoretically different from that of tumor cell-targeting since
      target angiogenic endothelial cells face the circulating blood. In addition, this
      strategy is expected to cause indirect tumor regression by disrupting angiogenic
      vessels. In this review, our recent studies are summarized to show the actual
      efficacy of angiogenic vessel-targeting delivery. We have developed various
      angiogenic vessel-targeted liposomes and evaluated them in experimental cancer
      models such as drug-resistant and hypovascular tumors. Our data indicate that
      increased apoptosis of angiogenic endothelial cells can be achieved by the
      targeted liposomes encapsulating cytotoxic drugs, resulting in enhanced
      anticancer effects. The advantages of angiogenic vessel-targeting are discussed
      based on our recent findings to provide an insight into why angiogenic vessels
      are a promising target for advanced cancer therapy.

PMID- 23123456
TI  - Advances in biology and toxicology of environmental metals/metalloids. Foreword.

PMID- 23123457
TI  - Selenometabolomics explored by speciation.
AB  - Selenium (Se) belongs to the same group as sulfur in the periodic table but
      possesses certain chemical properties characteristic of a metal. It is an
      essential element in animals but becomes severely toxic when the amount ingested
      exceeds the required level. On the other hand, Se is not essential in plants
      although some plants are Se hyperaccumulators. Se changes into several chemical
      forms when metabolized. Thus, the identification of selenometabolites would
      enable us to formulate a metabolic chart of Se. Recently, speciation analysis by
      hyphenated techniques has contributed immensely to the study of
      selenometabolomes, i.e., the entirety of selenometabolites. Indeed, speciation
      has unveiled some unique selenometabolites in biological samples. The aim of this
      review is to present newly identified selenometabolites in animals and plants by
      speciation using hyphenated techniques and to delineate the perspectives of Se
      biology and toxicology from the viewpoint of speciation.

PMID- 23123458
TI  - Role of arsenic (+3 oxidation state) methyltransferase in arsenic metabolism and
      toxicity.
AB  - The metabolism of arsenicals, including their reduction and methylation has been
      extensively studied, and both classical and novel pathways of arsenic methylation
      are proposed. Arsenic methylation has been considered to be a detoxification
      process of inorganic arsenicals, although recent studies have indicated that
      trivalent methylated arsenicals, the intermediate products of arsenic
      methylation, are more toxic than inorganic arsenicals. In 2002, arsenite (+3
      oxidation state) methyltransferase (As3MT) was discovered to be an enzyme
      responsible for arsenic methylation. This review focuses on current information
      on the function, genetic polymorphism, and alternative splicing of As3MT, all of
      which contribute to arsenic metabolism and toxicity.

PMID- 23123459
TI  - Molecular mechanisms of environmental organotin toxicity in mammals.
AB  - Organotins such as tributyltin are suspected of having multiple toxic effects in
      mammals, in addition to their endocrine-disrupting function. Endogenous organotin
      concentrations in human blood range from a few to a few hundred nM. In this
      review, we summarize recent findings on the mechanisms of toxicity of
      environmental organotins such as tributyltin (TBT) and triphenyltin (TPT) in
      mammals. TBT and TPT are potent inhibitors of mitochondrial ATP synthase, and a
      recent study suggests that TBT binds directly to ATP synthase. Organotins disturb
      steroid biosynthesis and degradation. TBT and TPT are dual agonists of retinoid X
      receptor (RXR) and peroxisome proliferator-activated receptor gamma (PPARgamma);
      they also induce the differentiation of adipocytes in vitro and in vivo, probably
      through PPARgamma activation, suggesting that they may work as obesogens.
      Environmental organotins are also neurotoxic; they induce behavioral abnormality
      and are toxic to the developing central nervous system. In vitro studies have
      shown that organotins induce intracellular Ca(2+) elevation and glutamate
      excitotoxicity. Recently, it was reported that endogenous levels of TBT decrease
      expression of 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic acid (AMPA)
      receptor subunit GluR2, leading to neuronal vulnerability. Most of the
      experimental studies have employed organotins at concentrations of uM order, and
      it remains important to clarify the molecular mechanisms of events induced by
      endogenous levels of environmental organotins.

PMID- 23123460
TI  - Role of intracellular defense factors against methylmercury toxicity.
AB  - Methylmercury (MeHg) is a causative agent of Minamata disease and an
      environmental pollutant that comprises a large portion of organically occurring
      mercury. Many aspects of the biological defense mechanisms against MeHg toxicity
      remain unclear. Recently, nuclear factor-E2-related factor 2 (Nrf2), heat shock
      factor protein 1 (Hsf1), and hydrogen sulfide were identified as intracellular
      defense factors against MeHg toxicity. These findings suggest that novel
      biological defense mechanisms against MeHg toxicity exist in the living organism.
      In addition, the expression of downstream genes that mediate activation of the
      transcription factors Nrf2 and Hsf1 was markedly induced by MeHg treatment,
      suggesting that this action is involved in the reduction of MeHg toxicity. On the
      other hand, when the gaseous form of hydrogen sulfide (H(2)S) binds directly to
      MeHg, bismethylmercury sulfide (MeHg-S-HgMe) as a low toxicity metabolite is
      formed. This suggests the involvement of the gaseous form of H(2)S in the
      reduction of MeHg toxicity. In this topic, we summarize the roles of factors
      involved in novel biological defense mechanisms against MeHg toxicity.

PMID- 23123461
TI  - Cellular defense mechanisms against lead toxicity in the vascular system.
AB  - Lead is a toxic heavy metal that can cause a range of health problems. In this
      context, the vascular system is a particular target of the deleterious effects of
      lead. Lead exerts its toxicity through substitution of other divalent cations
      such as calcium and zinc, resulting in disruption of homeostasis. Based on the
      evidence that lead up-regulates endoplasmic reticulum (ER) chaperone glucose
      regulated protein 78 (GRP78) and/or antioxidant proteins such as hemeoxygenase-1,
      it is believed that the heavy metal is able to induce ER and/or oxidative stress
      in cells. These events also suggest that the unfolded protein response (UPR)
      system and the antioxidant defense system Kelch-like ECH-associated protein 1
      nuclear factor (NF)-E2-related factor 2 (Keap1-Nrf2) play a critical role in
      adaptive response to lead. In this review, we summarize recent progress in lead
      toxicity in terms of cellular defense systems, including stress proteins and
      transcription factors involved in the vascular system.

PMID- 23123462
TI  - Cadmium renal toxicity via apoptotic pathways.
AB  - Cadmium is a nonessential heavy metal and ubiquitous potential environmental
      pollutant. Although the kidney proximal tubule is an important target for
      cadmium, the underlying cellular mechanisms of cadmium-induced renal toxicity
      remain elusive. Numerous studies have demonstrated that cadmium induces apoptotic
      cell death in various cell types via several apoptotic pathways, including
      mitochondria-mediated apoptotic cell death. In the epithelial cells of renal
      proximal tubules, cadmium can also induce apoptotic cell death in vivo and in
      vitro, which suggests that cell death of the epithelial cells through the
      apoptotic pathways is one of the key events in cadmium-induced renal toxicity. In
      this review, based upon the major findings of previous reports related to cadmium
      and apoptotic cell death, especially in the kidney and kidney proximal tubular
      cells, we present evidence for the current mechanisms of cadmium-induced renal
      toxicity via apoptotic cell death.

PMID- 23123463
TI  - Water extracts of immature Rubus coreanus regulate lipid metabolism in liver
      cells.
AB  - Hyperlipidemia is a major contributor for atherosclerosis and hypolipidemic drugs
      such as statin are highly prescribed to treat elevated lipid level in plasma.
      Rubus coreanus, which is widely cultivated in south eastern Asia, have been
      reported to show significant cholesterol lowering action in hyperlipidemic
      subjects. Our objective was to determine the cellular effect of Rubus coreanus
      extract (RCE) on cholesterol biosynthesis in human hepatic cells (HepG2) and to
      elucidate the molecular mechanism by which it causes change in cholesterol
      metabolism. RCE treatment lowered cholesterol biosynthesis as well as secretion
      from HepG2 cells. This effect was associated with lowering the release of
      apolipoproteins from hepatic cells. RCE treatment also showed an increase in
      phosphorylation of foxhead box protein 01 (FoXo-1) and 5-adenosine monophosphate
      activated protein kinase (AMPK), thus lowering expression of phosphoenolpyruvate
      carboxykinase (PEPCK) and G6Pase, which might be a major pathway for cholesterol
      biosynthesis inhibition. Apart from this; RCE also lowered sterol regulatory
      element-binding protein-1 (SREBP-1) expression in HepG2 cells, showing a long
      term regulation of cholesterol biosynthesis activity. These results indicate that
      one of the anti-hyperlipidemic actions of RCE is due to inhibition of cholesterol
      biosynthesis in hepatic cells and provides first documentation of a hypolipidemic
      bio-molecular action of Rubus coreanus.

PMID- 23123465
TI  - Involvement of phosphatidylinositol 3-kinase/Akt pathway in gemcitabine-induced
      apoptosis-like cell death in insulinoma cell line INS-1.
AB  - This study demonstrated gemcitabine-induced cytotoxicity in the insulinoma cell
      line INS-1. Gemcitabine inhibited INS-1 cell proliferation and maintained
      consistent cell number for 24 h, and then caused apoptosis within 48 h of
      incubation. Since gemcitabine activates the phosphatidylinositol 3-kinase (PI3
      K)/Akt pathway, which is involved in the resistance of pancreatic exocrine cancer
      to gemcitabine, we investigated the participation of this pathway in gemcitabine
      induced cytotoxicity in INS-1 cells. LY294002 and wortmannin, two PI3-K
      inhibitors, significantly prevented gemcitabine-induced cytotoxicity in INS-1
      cells, indicating that the PI3-K/Akt pathway is involved in gemcitabine-induced
      cytotoxicity. Gemcitabine-induced Akt phosphorylation in INS-1 cells was
      prevented by LY294002. Although gemcitabine induced cell cycle arrest at the G1
      and early S phases, LY294002 did not inhibit the cell cycle. These data suggest
      that PI3-K activation does not influence gemcitabine-induced cell cycle arrest.
      In gemcitabine-treated cells, nuclear fragmentation and DNA ladder formation were
      observed. These findings suggest that gemcitabine induced apoptotic cell death in
      INS-1 cells through the activation of the PI3-K/Akt pathway.

PMID- 23123464
TI  - Development of a novel and customizable two-solution mixing type spray nozzle for
      one-step preparation of nanoparticle-containing microparticles.
AB  - Production of drug nanoparticles is an effective strategy to enhance solubility
      and oral absorption of water-insoluble drugs. The handling of drug nanoparticles
      has been an important issue in drug formulation because nanoparticles easily
      aggregate each other and redispersion of these particles is very difficult. In
      the present study, we developed a unique two-solution mixing type spray nozzle
      that can prepare drug nanoparticles in microparticles in one step without any
      common solvent and surfactant, and then, the prepared formulation were evaluated.
      Ethylcellulose (EC) and mannitol (MAN) were used as a model polymer of water
      insoluble compound and a water-soluble carrier, respectively. We characterized
      the EC/MAN microparticles produced by the novel spray nozzle when customizing the
      nozzle parts to mix EC and MAN solution. Relatively smaller EC nanoparticles
      (<110 nm) in MAN microparticles (approximately 3 um) were obtained by changing
      the customizable parts in the nozzle. In addition, the core of EC nanoparticles
      (<50 nm) was also observed by atomic force microscopy. We also found that the
      mixing time in the nozzle parts affected the size and the standard deviation of
      EC nanoparticles. These results suggest that the size of EC nanoparticles in MAN
      microparticles is controllable by using this unique nozzle. After all, we could
      prepare MAN microparticles containing EC nanoparticles in one step by using the
      novel nozzle. The drug/MAN microparticles formulation produced by the nozzle may
      be useful for the handling of drug nanoparticles.

PMID- 23123466
TI  - Caffeic acid phenethyl ester suppresses the production of pro-inflammatory
      cytokines in hypertrophic adipocytes through lipopolysaccharide-stimulated
      macrophages.
AB  - Obesity is a condition in which excess body fat accumulates due to lipids
      producing adipocytes and an increased number of differentiated mature cells.
      Recently, new findings have shown that macrophages infiltrate into adipose
      tissues and produce various pro-inflammatory cytokines in obese subjects. The
      inflammatory changes induced by the cross-talk between adipocytes and macrophages
      are critical for the pathophysiology of obesity and thus of metabolic syndrome.
      Caffeic acid phenethyl ester (CAPE) is known to have many functions, including
      antibacterial, anticancer and anti-inflammatory properties, but there is no
      evidence of its effect on the inflammatory responses in hypertrophic adipocytes
      through stimulation by macrophages. We investigated the effect of CAPE on
      macrophages and hypertrophic adipocytes in this study. CAPE significantly
      suppressed the levels of lipopolysaccharide (LPS)-induced interleukin (IL)-1
      beta, tumor necrosis factor (TNF)-alpha and monocyte chemoattractant protein
      (MCP)-1 from a macrophage cell line, RAW264.7. Supernatants of stimulated
      RAW264.7 macrophages drastically increased mRNA levels of pro-inflammatory
      cytokines such as IL-6, MCP-1 and TNF-alpha in 3T3-L1 hypertrophic adipocytes.
      CAPE also significantly and dose-dependently reduced the gene expression of these
      cytokines. Our findings indicate that CAPE has inhibitory effects on the
      production of pro-inflammatory cytokines from LPS-stimulated RAW264.7
      macrophages. In addition, CAPE suppressed gene expressions of cytokines under
      inflammatory conditions of hypertrophic adipocytes, suggesting that it may have
      the potential to suppress inflammation by macrophage infiltration into adipose
      tissue in obese patients.

PMID- 23123467
TI  - Inhibitory effect of Shikonin on Candida albicans growth.
AB  - Our study showed that Shikonin (SK) could provide an action against almost all
      Candida albicans isolates tested. More importantly, to some Fluconazole (FCZ)
      resistant Candida albicans, the action of SK (MIC(80) value 4 ug/mL) was shown to
      be >16 times higher than that of FCZ (MIC(80) >64 ug/mL). To clarify the
      mechanism underlying this action, we performed a comparative study in untreated
      control C. albicans and C. albicans treated with SK. In this study, we found that
      SK treatment increased generation of endogenous reactive oxygen species (ROS) and
      decreased mitochondrial membrane potential. Furthermore, anti-oxidants N
      acetylcysteine (NAC) and glutathione (GSH) could reduce the antifungal activity
      of SK significantly in C. albicans. Our analyses also identified 9 differentially
      expressed genes, which were related to glycolysis-related genes (CDC19 and HXK2),
      fermentation-related genes (ALD5 and ADH1), antioxidant defense-related genes
      (SOD2 and SOD5), thioredoxin reductase-related gene (TRR1), mitochondrial
      respiratory electron transport chain-related gene (MRF1) and reduced nicotinamide
      adenine dinucleotide phosphate (NADPH) oxidoreductase-related gene (EBP1). These
      results suggest that mitochondrial aerobic respiration shift and endogenous ROS
      augmentation contribute to the action of SK against C. albicans.

PMID- 23123468
TI  - Very long chain fatty acid beta-oxidation in astrocytes: contribution of the
      ABCD1-dependent and -independent pathways.
AB  - Very long chain fatty acid (VLCFA) metabolism in astrocytes is important for the
      maintenance of myelin structure in central nervous system. To analyze the
      contribution of the ABCD1-dependent and -independent pathways to VLCFA metabolism
      in astrocytes, we prepared human glioblastoma U87 cells with a silencing of ABCD1
      and primary astrocytes from abcd1-deficient mice, and measured fatty acid beta
      oxidation in the presence or absence of a potent inhibitor of carnitine
      palmitoyltransferase I, 2-[5-(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA).
      In U87 cells, C24:0 beta-oxidation was decreased to ca. 70% of the control in the
      presence of POCA, and the activity was further decreased to ca. 20% by the
      silencing of ABCD1. In mouse primary astrocytes, C24:0 beta-oxidation was also
      decreased to ca. 70% of the control in the presence of POCA. The C24:0 beta
      oxidation in Abcd1-deficient primary astrocytes was ca. 60% of the wild-type
      cells and the activity was further decreased to ca. 25% in the presence of POCA.
      Compared to human skin fibroblasts, in which VLCFA beta-oxidation is not
      significantly inhibited by POCA, approximately one-third of the overall VLCFA
      beta-oxidation was inhibited in both types of astrocytic cells. These results
      suggest that VLCFA is indeed beta-oxidized in ABCD1-dependent pathway, but the
      ABCD1-independent peroxisomal and mitochondrial beta-oxidation pathways
      significantly contribute to VLCFA beta-oxidation in astrocytic cells.

PMID- 23123469
TI  - The role of acetoacetyl-CoA synthetase, a ketone body-utilizing enzyme, in 3T3-L1
      adipocyte differentiation.
AB  - Acetoacetyl-CoA synthetase (AACS) is a ketone body-utilizing enzyme that converts
      acetoacetate to acetoacetyl-CoA in the cytosol and consequently provides acetyl
      units as the precursors for lipogenesis. To clarify the role of AACS in
      adipogenesis, we investigated the expression and localization of the AACS protein
      and the effect of AACS knockdown on 3T3-L1 differentiation. The protein
      expression of AACS is dramatically induced during 3T3-L1 differentiation and is
      localized in the cytoplasm of differentiated 3T3-L1 cells. Moreover, knockdown of
      AACS inhibits differentiation of 3T3-L1 cells and suppresses expression of the
      adipocyte markers, peroxisome proliferator-activated receptor gamma (PPARgamma)
      and CCAAT/enhancer binding protein alpha (C/EBPalpha). These results suggest that
      AACS has a crucial role in the mechanism of 3T3-L1 differentiation.

PMID- 23123470
TI  - Qingkailing injection alleviates experimental autoimmune uveitis in rats via
      inhibiting Th1 and Th17 effector cells.
AB  - Qingkailing injection is a well-known composite formula of traditional Chinese
      medicine and is commonly used in clinical practice, which could offer
      immunomodulatory effect from our clinical experience on uveitis treatment by
      Qingkailing. We did the experiment in order to investigate the curative effect
      and mechanism of Qingkailing injection to rat experimental autoimmune uveitis
      (EAU). EAU was induced in Lewis rats by immunization IRBP1177-1191 in complete
      Freund's adjuvant in multi-point. We found that Qingkailing injection can
      alleviate autoimmune uveitis in rats, inhibit the differentiation toward Th1 and
      Th17 effector cells and the relevant cytokines secretion. The therapeutic effect
      may also be regulated through increased secretion of interleukin (IL)-10.

PMID- 23123471
TI  - Gomisin A enhances tumor necrosis factor-alpha-induced G1 cell cycle arrest via
      signal transducer and activator of transcription 1-mediated phosphorylation of
      retinoblastoma protein.
AB  - Gomisin A, a dibenzocyclooctadiene lignan isolated from the fruit of Schisandra
      chinensis, has been reported as an anti-cancer substance. In this study, we
      investigated the effects of gomisin A on cancer cell proliferation and cell cycle
      arrest in HeLa cells. Gomisin A significantly inhibited cell proliferation in a
      dose-dependent manner after 72 h treatment, especially in the presence of tumor
      necrosis factor-alpha (TNF-alpha), due to cell cycle arrest in the G1 phase with
      the downregulation of cyclin D1 expression and Retinoblastoma (RB)
      phosphorylation. In addition, gomisin A in combination with TNF-alpha strongly
      suppressed the expression of signal transducer and activator of transcription 1
      (STAT1). Inhibition of STAT1 pathways by a small-interfering RNA against STAT1
      and AG490 Janus kinase (JAK) kinase inhibitor AG490 reduced the cyclin D1
      expression and RB phosphorylation, indicating that JAK-mediated STAT1 activation
      is involved in gomisin A-induced G1 cell cycle arrest.

PMID- 23123472
TI  - Assessment of substrate inhibition of bacterial oligopeptidase B.
AB  - Oligopeptidase B (OPB; EC 3.4.21.83) from 2 Gram-negative bacteria,
      Stenotrophomonas maltophilia (Stm) and Serratia marcescens (Sem), and the Gram
      positive bacterium Rhodococcus erythropolis (Re) were cloned and characterized to
      clarify their activities and substrate specificities using peptidyl-MCA
      substrates containing Arg or Lys. The cloned enzymes, Stm, Sem and ReOPBs, in
      addition to Escherichia coli OPB (EcOPB) were expressed using a pET expression
      system. Although the Stm and SemOPBs share 45% sequence identity to each other
      and up to 60% identity with respect to their catalytic domains, their activities
      towards MCA substrates were quite different. StmOPB is approximately 100-500
      times more active than SemOPB and 3-30 times more active than EcOPB. The activity
      of ReOPB is comparable to that of StmOPB and it shares 40% and 36% identity to
      StmOPB and SemOPB, respectively. Some features of Stm, Re and EcOPBs are similar
      to those of previously cloned OPBs, which were also strongly inhibited by
      substrates, but SemOPB differs from all other OPBs in that it is not inhibited by
      substrates; even substrates containing double arginine at 35 uM did not inhibit
      SemOPB. On the other hand, the same substrates at only 5 uM inhibited the
      activity of the Stm, Re, and EcOPB. This phenomenon was not observed with
      substrates containing single or double lysine.

PMID- 23123473
TI  - RecQ5 interacts with Rad51 and is involved in resistance of Drosophila to
      cisplatin treatment.
AB  - RecQ5 is a member of the RecQ family of DNA helicases. There are 5 RecQ members
      in humans. Defects in 3 of them, i.e., BLM, WRN, and RTS, cause Bloom, Werner,
      and Rothmund-Thomson syndromes, respectively. RECQL1 and RECQL5 have not been
      associated with any human disease, and their precise roles are unknown. Our
      previous study suggests that the lack of RecQ5, which is the Drosophila homolog
      of RECQL5, leads to the accumulation of DNA double-stranded breaks (DSBs). It is
      possible that RecQ5 is involved in DSB repair. However, little is known about
      this possible function of RecQ5 in DSB repair. Here, we report that Rad51
      protein, which plays a critical role in DSB repair, interacted with RecQ5 in
      vitro and in vivo in Drosophila. The Rad51 protein interacted with the C-terminal
      region of RecQ5, as shown by the yeast two-hybrid method. Moreover, the C
      terminal region of the RecQ5 protein and the central region of Rad51 interacted
      directly and specifically when examined by the glutathione-S-transferase pull
      down method. Consistent with these results, when RecQ5 and Rad51 were co
      expressed in Drosophila cells in culture, they became co-localized in nuclei and
      could be co-immunoprecipitated. Furthermore, RecQ5-deficient flies (recq5) were
      more sensitive to the chemotherapeutic agent cisplatin compared with wild-type
      ones. Also, Rad51 mutants (rad51) were more sensitive to cisplatin, with
      sensitivity similar to that of recq5 rad51 double mutants. These data suggest
      that RecQ5 and Rad51 in Drosophila functioned for survival after the flies had
      been treated with cisplatin.

PMID- 23123474
TI  - Comparison of contamination levels on the exterior surfaces of vials containing
      platinum anticancer drugs in Japan.
AB  - Contamination of the external surface of anticancer drug vials supplied to
      hospital pharmacies has been recognized as a potential health hazard. The aim of
      this study was to investigate the levels of contamination on the exterior surface
      of vials containing platinum anticancer drugs in Japan. Platinum contamination on
      the exterior surface of vials containing cisplatin or carboplatin was examined
      using products commercially available in Japan. Cisplatin vials from 42 batches
      (2 drug contents, 10 products and 5 manufacturers) and carboplatin vials from 28
      batches (3 drug contents, 7 products and 3 manufacturers) were used. Five vials
      were randomly sampled from each batch. Exterior contamination levels of 0.070-144
      ng/vial as cisplatin and 0.21-1630 ng/vial as carboplatin were detected.
      Significant differences in the levels of contamination among the batch numbers
      were observed in 6 of 10 cisplatin products and 6 of 7 carboplatin products.
      Significant differences in the levels of contamination were observed in 3
      cisplatin products with different contents of drug within the vials and 1
      carboplatin product with different contents of drug within the vials. Significant
      differences in the contamination levels among the cisplatin manufacturers but not
      carboplatin manufacturers were observed. The degree of contamination of the
      carboplatin products was significantly higher than that of the cisplatin
      products. In conclusion, external contamination was confirmed in all cisplatin
      and carboplatin vials tested. The degree of contamination was different among
      different batch numbers, drug contents, manufacturers, and platinum anticancer
      drug.

PMID- 23123475
TI  - Alterations of plasma levels of lysophosphatidic acid in response to fasting of
      rats.
AB  - The aim of this study was to investigate the effect of fasting on in vivo plasma
      levels of lysophosphatidic acid (LPA), a physiologically important
      lysophospholipid mediator. We assayed to measure activities of an LPA-producing
      enzyme (lysophospholipase D) and LPA-degrading enzyme activities
      (lysophspholipase A, lipid phosphate phosphatase) in rat plasma or blood, by
      measuring choline, fatty acid and inorganic phosphate, respectively. Both LPA and
      its precursor lysophosphatidylcholine (LPC) were quantified by liquid
      chromatography-tandem mass spectrometry. Fasting of rats for 24 h decreased
      plasma concentrations of oleoyl-, linoleoyl-, arachidonoyl- and docosahexaenoyl
      LPAs, but not palmitoyl- and stearoyl-LPAs, possibly due to decreased levels of
      corresponding LPCs in the plasma and elevated lipid phosphate phosphatase
      activity for LPAs in the blood. Our results indicate that the in vivo circulating
      levels of LPAs in rats are affected by fasting.

PMID- 23123476
TI  - A novel C-C chemokine receptor 2 antagonist prevents progression of albuminuria
      and atherosclerosis in mouse models.
AB  - C-C chemokine ligand 2 (CCL2)/its receptor (CCR2) axis is considered as an
      important signaling pathway in inflammatory diseases. TLK-19705 is a novel CCR2
      antagonist, (1-(1,3-dimethyl-1-H-pyrazolo[3,4-b]pyridine-5-carbonyl)-3-(4-fluoro
      3-(trifluoromethyl)phenyl)urea), and the inhibitory activity was antagonized by
      the third extracellular loop peptide of CCR2. We examined in this study the
      effects of TLK-19705 on diabetic nephropathy and atherosclerosis in mouse models.
      Treatment with TLK-19705 (30 mg/kg/d) for 8 weeks ameliorated urinary albumin
      creatinine ratio in db/db mice. In addition, TLK-19705, given at 10 mg/kg/d for 8
      weeks, significantly reduced the areas of atherosclerotic lesion in
      apolipoprotein E knockout mice. In conclusion, the results of this study indicate
      not only considerable therapeutic potential of CCR2 antagonists for diabetic
      nephropathy and atherosclerosis, but also that TLK-19705 would serve as a
      powerful tool in mechanistic investigation of these inflammatory diseases.

PMID- 23123477
TI  - Inhibition of human aldose reductase-like protein (AKR1B10) by alpha- and gamma
      mangostins, major components of pericarps of mangosteen.
AB  - A human member of the aldo-keto reductase (AKR) superfamily, AKR1B10, was
      recently identified as both diagnostic marker and therapeutic target in the
      treatment of several types of cancer. In this study, we have examined AKR1B10
      inhibition by five xanthone derivatives, components of pericarps of mangosteen,
      of which alpha- and gamma-mangostins show potential anti-cancer properties. Among
      the five xanthones, gamma-mangostin was found to be the most potent competitive
      inhibitor (inhibition constant, 5.6 nM), but its 7-methoxy derivative, alpha
      mangostin, was the second potent inhibitor (inhibition constant, 80 nM).
      Molecular docking of the two mangostins in AKR1B10 and site-directed mutagenesis
      of the putative binding residues revealed that Phe123, Trp220, Val301 and Gln303
      are important for the tight binding of gamma-mangostin, and suggested that the 7
      methoxy group of alpha-mangostin impairs the inhibitory potency by altering the
      orientation of the inhibitor molecule in the substrate-binding site of the
      enzyme.

PMID- 23123478
TI  - Polyethylene glycol prevents in vitro aggregation of slightly negatively-charged
      liposomes induced by heparin in the presence of bivalent ions.
AB  - Liposomes are of great interest as drug delivery vehicles, and studies have
      focused on understanding how the physical and chemical characteristics of
      liposomes can be modified to improve their in vivo behavior. In a previous study,
      we found that the slightly negatively-charged liposomes aggregate only in the
      culture medium of human umbilical vein endothelial cells, whereas the liposomes
      modified with polyethylene glycol (PEG) (PEGylated) did not aggregate. In the
      present study, we investigated the underlying mechanism of this phenomenon.
      Firstly, it was found that heparin in the culture medium is one of the factors
      that cause aggregation of the non-PEGylated liposomes. Since the addition of
      ethylenediaminetetraacetic acid (EDTA) prevented the aggregation, metal ions,
      such as Ca(2+) and Mg(2+), in the culture medium could also be important in
      driving the aggregation. In the presence of heparin, higher concentrations of
      Ca(2+) or Mg(2+) increased the particle size of the non-PEGylated liposomes,
      although no change in the particle size of PEGylated liposomes was observed.
      Under conditions in which aggregation occurred, we measured the binding and
      uptake of liposomes by macrophages in vitro. The binding and uptake of non
      PEGylated liposomes were significantly increased with increasing Ca(2+)
      concentrations, whereas those of PEGylated liposomes were unchanged. While the
      formation of aggregations of cationic or anionic liposomes has been reported
      previously, there are few reports addressing the aggregation of slightly
      negatively-charged or neutral liposomes. Thus, our data provide useful insights
      on the effect of PEGylation on liposomal aggregation and in vivo behavior.

PMID- 23123479
TI  - Reinvestigation of drugs and chemicals as aquaporin-1 inhibitors using pressure
      induced hemolysis in human erythrocytes.
AB  - Recently, we have found that pressure-induced hemolysis is enhanced by inhibiting
      water transport via aquaporin-1 (AQP1), as seen in p-chloromercuribenzoate (pCMB)
      treated erythrocytes. So, using this method we reinvestigated the functions as
      AQP1 inhibitors of drugs and chemicals such as acetazolamide, sodium
      nitroprusside, tetraethylammonium ions (TEA(+)), and dimethylsulfoxide (DMSO).
      The values of hemolysis at 200 MPa were almost unaffected by acetazolamide or
      sodium nitroprusside, decreased by TEA(+), and increased significantly by DMSO.
      Furthermore, the erythrocytes were exposed to pCMB in the presence of TEA(+) or
      DMSO. The enhancement effect of pCMB on pressure-induced hemolysis was unaffected
      by TEA(+) but attenuated by DMSO. Taken together, these results suggest that, of
      drugs and chemicals examined here, DMSO only is an AQP1 inhibitor, but the effect
      of DMSO is small compared with pCMB.

PMID- 23123480
TI  - 2,3,22,23-tetrahydroxyl-2,6,10,15,19,23-hexamethyl-6,10,14,18-tetracosatetraene,
      an acyclic triterpenoid isolated from the seeds of Alpinia katsumadai, Inhibits
      acyl-CoA : cholesterol acyltransferase activity.
AB  - In order to isolate a cholesterol-lowering compound from Alpinia katsumadai, an
      inhibitor for acyl-CoA : cholesterol acyltransferase (ACAT), an enzyme
      responsible for the cholesterol ester formation in liver, was purified, its
      chemical structure was determined, and in vivo and in vitro inhibition activities
      were performed. In a high fat diet mouse model, we discovered that the ethanol
      extract of Alpinia katsumadai reduced plasma cholesterol, triglyceride, and low
      density lipoprotein (LDL) levels. An acyclic triterpenoid showing ACAT inhibitory
      activity was isolated from the extract of seeds of A. katsumadai. By NMR
      spectroscopic analysis of its (1)H-NMR, (13)C-NMR, (1)H-(1)H correlation
      spectroscopy, heteronuclear multiple bond connectivity (HMBC), hetero
      multiquantum coherence (HMQC) and nuclear Overhauser effect, chemical structure
      of 2,3,22,23-tetrahydroxyl-2,6,10,15,19,23-hexamethyl-6,10,14,18
      tetracosatetraene (1), were elucidated. The acyclic triterpenoid was found to be
      responsible for the ACAT inhibition activities of rat liver microsomes with
      IC(50) values of 47.9 uM. It also decreased cholesteryl ester formation with
      IC(50) values of 26 uM in human hepatocyte HepG2 cell. The experimental study
      revealed that the ethanol extract of A. katsumadai has a hypolipemic effect in
      high fat diet mice, and the isolated acyclic triterpenoid has ACAT inhibition
      activity, showing a potential novel therapeutic approach for the treatment of
      hyperlipidemia and atherosclerosis.

PMID- 23123481
TI  - Anti-tumor effects of cationic hybrid liposomes against colon carcinoma along
      with apoptosis in vitro.
AB  - New-type three-component cationic hybrid liposomes (HLs) composed of
      dimyristoylphosphatidylcholine (DMPC), polyoxyethylene(21)dodecyl ether
      (C(12)(EO)(21)) and O,O'-ditetradecanoyl-N-(alpha-trimethylammonioacetyl)
      diethanolamine chloride (2C(14)ECl) were produced. Cationic HLs were smaller and
      more stable than pure DMPC liposomes. It is noteworthy that cationic HLs could
      remarkably inhibit the growth of human colon cancer (HCT116) cells along with
      apoptosis in vitro for the first time in this study.

PMID- 23123482
TI  - Social relationships and dental care service utilization among older adults.
AB  - OBJECTIVE: This study described the association between dental care service
      utilization and two domains of social relationships (social integration and
      social support) among older adults. METHODS: The study employed data from the
      2008 Health and Retirement Study, examining regression models for whether a
      person visited a dentist in the past 2 years, including adjustments for
      demographic, socioeconomic, and health characteristics. RESULTS: Social
      interaction, social participation, neighborhood cohesion, and marital status were
      related to an increased likelihood of having visited a dentist. Older persons
      exhibiting loneliness and having received financial aid from network members
      demonstrated a decreased likelihood of visiting a dentist. The increased
      likelihood of visiting a dentist when a child lives nearby only occurred after
      introducing health covariates. DISCUSSION: The article discusses the implications
      of the study findings as they relate to social relationships and oral health and
      recommends some additional research directions to explore the etiology of dental
      care use.

PMID- 23123483
TI  - First-hand impressions.

PMID- 23123484
TI  - Intermittent self-catheterisation:  past, present and future.
AB  - In the past, the only way to drain a bladder was to use intermittent
      catheterisation. For four millennia, intermittent self-catheterisation (ISC) was
      used to treat bladder dysfunction. That changed in the 20th century when Foley
      redesigned and improved on 19th century designs for an indwelling urethral
      catheter. While some patients benefit from indwelling catheters, long- and short
      term indwelling catheters can increase infection risks and contribute to bladder
      dysfunction. NICE guidance on infection control recommends that intermittent
      catheterisation should be used in preference to an indwelling catheter if it is a
      clinically appropriate and practical option for the patient. NICE also recommends
      that patients should be offered a choice of either single-use hydrophilic or gel
      reservoir catheters for intermittent self-catheterisation. Voiding problems
      increase the risks of infection, bladder and renal dysfunction, and can impair
      quality of life. Individuals who have reasonable bladder capacity and sufficient
      dexterity and motivation can regain bladder control using ISC, which can make a
      huge difference to their health and wellbeing.

PMID- 23123485
TI  - OptiLube Active. The role of lubricants in urinary catheterisation.
AB  - Catheterisation is necessary for many patients but places them at risk of
      developing uncomfortable and potentially lethal infections. Catheter insertion
      can also be painful. It is essential that all staff who perform the procedure
      have a clear understanding of the measures they should implement to reduce
      discomfort, trauma and the risk of infection to the patient. The need for staff
      to be trained and competent and to use an aseptic technique when undertaking the
      procedure are core principles for practice. Guidance advises that lubricating
      gels are used in all patients undergoing urethral catheterisation to minimise the
      risk of urethral trauma and associated infection. Gels containing a local
      anaesthetic make the procedure less uncomfortable, but must be applied correctly
      to be effective. This article will consider the actions of these gels and the
      potential benefits and risks associated with each, focusing on use of OptiLube
      Active with case studies.

PMID- 23123486
TI  - Are GPs ready to talk  about death and dying?

PMID- 23123487
TI  - The diabetic foot: an overview for community nurses.
AB  - Diabetic foot problems are a common complication of diabetes. They can lead to
      much morbidity and some mortality, with foot disease the leading cause of non
      traumatic lower-limb amputation in the developed world. Diabetic foot disease is
      a result of three main pathologies, which can occur singly or in combination:
      diabetic peripheral neuropathy, peripheral arterial disease and infection. The
      consequences of these pathologies are ulceration, Charcot foot, painful diabetic
      neuropathy, gangrene and amputation. This article offers a podiatrist's view of
      the management of diabetic foot problems, from initial assessment to the
      management of complex disease. Patients with a diabetic foot problem must be
      assessed thoroughly and referred to the local multidisciplinary team where
      appropriate. Recurrence of ulcers is common, so good foot health education,
      adequate footwear and regular podiatry (if necessary) must be an integral part of
      the patient's review process. Community nurses are often the first to detect a
      diabetic foot ulcer in housebound patients, so they need the necessary skills to
      manage the ulcer effectively and refer patients appropriately.

PMID- 23123488
TI  - Understanding residential home  issues to meet health-care needs.
AB  - The needs of individuals in residential care homes have risen over time.
      Residential care homes were originally set up to provide accommodation for those
      requiring limited support, but today residents often have high levels of both
      health and social care needs, which often go unmet. The suggestion often made is
      that more staff training and improved support are needed. This is an
      oversimplification, as a number of other factors have a significant impact on
      care provision. It is suggested that residents will continue to receive
      suboptimal care until the issues are acknowledged and tackled.

PMID- 23123489
TI  - The role of the pharmacy technician  in the skill-mixed district nursing team.
AB  - Registered nurses in the district nursing service delegate a broad range of
      medication administration activities to healthcare assistants. Although
      healthcare assistants have provided extra capacity, not all activities are
      suitable for delegation to unregulated practitioners. At the same time, their
      competency assessment is often patient-specific and demands significant
      registered nursing input. The purpose of this 6-month pilot programme was to test
      the premise that the employment of a pharmacy technician in the district nursing
      service would enhance productivity levels and deliver cost savings. Activities
      delegated included the administration of oral tablets and subcutaneous insulin
      and low molecular weight heparin injections. The evaluation found that the
      introduction of the pharmacy technician was associated with neither enhanced
      productivity nor more than modest cost savings. However, role redesign is a long
      term activity and their role could be built on with further competency analysis.

PMID- 23123490
TI  - Medicines law overhaul with  Human Medicines Regulations 2012.
AB  - The Human Medicines Regulations 2012 are a major consolidation of medicines law.
      They largely replace the Medicines Act 1968 and some 200 further pieces of
      secondary legislation, including the Prescription Only Medicines (Human Use)
      Order 1997 that defined and set out the authority of non-medical prescribers.
      Although the 2012 regulations mainly consolidate medicines law into one piece of
      secondary legislation it does introduce some policy changes that will influence
      district nurse practice by allowing non-medical prescribers to issue patient
      specific directions in primary care settings and allowing community pharmacists
      to make changes to a prescription without the need to contact the prescriber
      beforehand.

PMID- 23123491
TI  - Self-management: helping patients take the first steps to get back to work.

PMID- 23123492
TI  - An Olympic legacy?

PMID- 23123493
TI  - Prevalence of classic signs and symptoms of rickets and vitamin D deficiency in
      Mongolian children and women.
AB  - In order to assess the current nutrition status of Mongolian population,
      including rickets and vitamin D deficiency of children and women, the Fourth
      National Nutrition Cross-Sectional Survey was conducted in 21 aimags (provinces)
      of 4 economic regions of the country and capital city Ulaanbaatar in 2010.
      Children of age under five years, and non-pregnant women of reproductive age were
      used as subjects for assessing rickets and vitamin D deficiency. A total of 400
      households were randomly selected from each of 4 economic regions and Ulaanbaatar
      city. Clinical examinations were performed on 706 children of age under five
      years. Interviews were used to assess vitamin D supplement use. The serum level
      of 25-hydroxyvitamin D was measured in 524 children aged 6-59 months and in 867
      women of reproductive age. This survey found that 21.8% of children had vitamin D
      deficiency, 20.6% had low vitamin D reserve, and 30.0% of women had vitamin D
      deficiency and 22.2% had low vitamin D reserve. The prevalence of vitamin D
      deficiency in children (35.0%, 95% CI, 24.7-47.0) and women (54.9%, 95% CI 45.5
      64.0) in the Eastern Region was (35.0%, 95% CI, 24.7-47.0) significantly higher
      than in the Western, Khangai, Central Regions, and Ulaanbaatar. Further it was
      found that 27.4% of children under-two years had received vitamin D
      supplementation. The proportion of children, who did not receive vitamin D
      supplementation had a higher prevalence of vitamin D deficiency than that of the
      children of the Eastern Region. None of the women who were involved in this
      survey had received vitamin D supplementation; 10.2% of them had delivered in the
      past 12 months, and 22.5% were breastfeeding. The prevalence of classic signs and
      symptoms of rickets were commonly reported among children of age under five, and
      skeletal abnormalities more commonly reported in children aged 12-47 months. In
      conclusion, there is a high prevalence of classic signs and symptoms of rickets
      in children of age under five years. Vitamin D supplementation in adequate doses
      for the prevention and treatment of rickets in children is insufficient. Thus, a
      trial survey is needed to assess the safe and effective doses of vitamin D
      supplementation necessary for the maintenance of normal serum 25-hydroxyvitamin D
      concentrations in Mongolian children, and women. In addition, a vitamin D food
      fortification program is required. This article is part of a Special Issue
      entitled 'Vitamin D Workshop'.

PMID- 23123494
TI  - Fluoride release and anti-erosive effects of dentifrices containing PVM/MA
      copolymers.
AB  - OBJECTIVE: To evaluate fluoride release from dentine discs and study the effects
      of dentine tubule occlusion and erosion prevention of dentifrices containing
      fluoride and PVM/MA copolymers in a cycling erosive challenge model. METHODS:
      Human dentine discs, 15 in each group, were eroded by 1.0% citric acid and
      treated by ProNamel((r)) (PRN, 1450ppm fluoride), Colgate((r)) Total Sensitive
      (CTS, 1100ppm fluoride), a prototype dentifrice containing 5000ppm fluoride and
      2% PVM/MA copolymers (PVD) and distilled water (control). Fluoride release from
      each dentine disc was evaluated every 2h in a 12-h period. For cycling erosive
      challenges, dentine discs were treated by dentifrice slurries twice daily,
      followed by immersion in saliva and erosive challenges by orange juice. Dentine
      discs were stored in saliva between treatment cycles and the cycling erosive
      challenges were repeated for 15 days. On days 5, 10, and 15, size of dentine
      tubule openings and level of dentine tubule occlusion were evaluated with a 3D
      scanning microscope. RESULTS: PVD released more fluorides than other dentifrices
      in a 12-h period (p<0.05). CTS released more fluorides than PRN at 2, 4, 6, and
      8h following a single application (p<0.05). The size of the dentine tubules was
      smaller and the number of occluded dentine tubules was greater in the CTS and PVD
      groups than those in the control and PRN groups on day 15 of the erosive
      challenges. CONCLUSION: Bioadhesive PVM/MA copolymers facilitate fluoride
      retention and release from dentine discs, and promote dentine tubule occlusion
      and erosion prevention when combined with hydrated silica particles.

PMID- 23123496
TI  - Effect of endodontic sealers on tooth color.
AB  - OBJECTIVES: One of the goals of endodontic treatment is the adequate filling of
      the root canal,which is often done using gutta-percha and sealer. It has been
      reported that sealer remnants in the coronary pulp chamber cause tooth color
      changes. Therefore, this study was designed to examine the effect of endodontic
      sealer remnants on tooth color, testing the hypothesis that sealers cause coronal
      color changes. METHODS: Forty single-rooted human teeth were endodontically
      treated leaving excess sealer material in the coronary pulp chamber. The
      specimens were divided into four groups (n = 10) according to the endodontic
      sealer used (AH, AH Plus; EF, Endofill; EN,endome' thasoneN; and S26, Sealer 26).
      Teeth were stored at 37 8C moist environment.Color coordinates (L*a*b*) were
      measured with a spectrophotometer before endodontic treatment(baseline-control),
      24 h and 6 months after treatment. L*a*b* values were used to calculate color
      changes (DE). Data were statistically analyzed using Kruskal-Wallis and Mann
      Whitney-U tests. RESULTS: Color changes were observed for all groups with S26 and
      EN producing the greatest mean DE values after 6 months. CONCLUSION: Endodontic
      sealer remnants affect tooth color confirming the experimental hypothesis.
      CLINICAL SIGNIFICANCE: This study examined the effect of endodontic sealer
      remnants on tooth color, and observed that after 6 months, the sealers produced
      unacceptable color changes.

PMID- 23123495
TI  - In vitro and in vivo investigation of the biological and mechanical behaviour of
      resin-modified glass-ionomer cement containing chlorhexidine.
AB  - OBJECTIVES: To evaluate: (1) the in vitro antibacterial, cytotoxic and mechanical
      properties of a resin-modified glass ionomer cement (RMGIC) containing different
      concentrations of chlorhexidine (CHX) and (2) the in vivo microbiologic action of
      the best concentration of CHX associated with the RMGIC applied on remaining
      dentine after indirect pulp treatment (IPT). METHODS: For the in vitro studies,
      RMGIC was associated with 0.2, 0.5, 1.25 and 2.5% CHX. Microbiologic evaluation
      consisted of an agar diffusion test on cariogenic bacteria for 24h. Odontoblast
      like cell metabolism and morphology analyses measured the cytotoxic effects of
      the RMGIC groups after 24h. The same groups were submitted to compressive and
      diametral tensile strength. The in vivo treatment consisted of IPT using an RMGIC
      associated with the best CHX concentration. Clinical and microbiologic
      evaluations were performed before and after 3 months. RESULTS: The use of 1.25%
      CHX significantly improved the antibacterial effects of the evaluated RMGIC,
      without causing any detrimental effects to the odontoblast-like cells and on the
      mechanical properties. This RMGIC and CHX combination completely eliminated
      mutans streptococci after 3 months of IPT. CONCLUSION: The RMGIC and 1.25% CHX
      mixture showed great biological and mechanical behaviour and could be a good
      treatment against caries progression. CLINICAL SIGNIFICANCE: The association of
      CHX with a liner RMGIC opens a new perspective for arresting residual caries
      after IPT.

PMID- 23123498
TI  - The detection and quantification of ethyl glucuronide in placental tissue and
      placental perfusate by headspace solid-phase microextraction coupled with gas
      chromatography-mass spectrometry.
AB  - BACKGROUND: Ethyl glucuronide (EtG) is arising as a promising biomarker of heavy
      prenatal alcohol exposure, however its transfer across the human placenta is
      still unclear and is currently being investigated using the ex vivo placental
      perfusion model. This model allows for sampling from placental tissue and
      placental perfusate, which is a surrogate to plasma. OBJECTIVE: To develop a
      method for detecting and quantifying EtG in placental perfusate and tissue using
      headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography
      mass spectrometry (GC-MS). METHODS: A method was optimized by manipulation of the
      following components to attain the highest peak counts for the quantifying ions
      of EtG and its deuterated internal standard on the mass spectrum: cartridges used
      for solid phase extraction, injection method, derivatizing agent, pre-injection
      parameters, SPME fiber, GC ramp speed, and GC column flow. RESULTS: The final
      method utilized involved solid phase extraction of standards via UCT CleanScreen
      Cartridges, derivatization with heptafluorobutyric acid, and introduction into
      the GC via HS-SPME with adsorption to a polydimethylsiloxane fiber. The method
      has improved sensitivity over other methods that quantify EtG in blood using GC
      MS, with detection limits of 1.6 ng/mL and 13.7 ng/g for placental perfusate and
      tissue, respectively. The method was applied to samples collected from the fetal
      reservoir during the ex vivo placental perfusion model and EtG was detected in
      the fetal circulation after 20 minutes of perfusion, indicating transfer of EtG.
      CONCLUSIONS: The present method is sensitive and can be used to quantify EtG
      transfer during ex vivo placental perfusion experiments.

PMID- 23123497
TI  - A preliminary investigation into the use of denture adhesives combined with
      dietary advice to improve diets in complete denture wearers.
AB  - OBJECTIVES: To investigate how nutritional advice and denture adhesives may be
      associated with eating healthier foods. METHODS: 35 edentulous subjects (13 males
      and 22 females, mean age 73.9 years (55-84 years)), wearing complete dentures
      more than one year old, completed validated questionnaires analysing saturated
      fat, protein, Vitamin C, the number of servings of fruit/vegetables. In addition
      subjects completed the NDNS and OHIP Edent questionnaires. At baseline,
      nutritional information and the use of denture adhesive was provided. Subjects
      returned after 30 consecutive days and the questionnaires were repeated. A
      Wilcoxon signed rank test was used to test the effect of the denture adhesive on
      diet and on quality of life measures. RESULTS: The subjects increased mean intake
      from 2.2 portions of fruit/vegetables a day to 3.6. Fat and saturated fats were
      reduced from 23.2g to 11.3g and Vitamin C intake increased by 34.4mg. All were
      statistically significant (p<0.0001). There was a statistically significant
      improvement over the 30-day treatment period in subjects' ability as measured by
      using OHIP Edent scores to bite (p=0.017) and chew a range of foods (p=0.007).
      CONCLUSION: Within the confines of the study, use of simple dietary advice and
      denture adhesives improved diet. CLINICAL SIGNIFICANCE: The results of this pilot
      study suggest that denture fixatives may improve dietary behaviour of complete
      denture wearers.

PMID- 23123499
TI  - Signaling pathways bridging microbial-triggered inflammation and cancer.
AB  - Microbial-triggered inflammation protects against pathogens and yet can
      paradoxically cause considerable secondary damage to host tissues that can result
      in tissue fibrosis and carcinogenesis, if persistent. In addition to classical
      pathogens, gut microbiota bacteria, i.e. a group of mutualistic microorganisms
      permanently inhabiting the gastrointestinal tract and which plays a key role in
      digestion, immunity, and cancer prevention, can induce inflammation-associated
      cancer following the alterations of their microenvironment. Emerging experimental
      evidence indicates that microbiota members like Escherichia coli and several
      other genotoxic and mutagenic pathogens can cause DNA damage in various cell
      types. In addition, the inflammatory response induced by chronic infections with
      pathogens like the microbiota members Helicobacter spp., which have been
      associated with liver, colorectal, cervical cancers and lymphoma, for instance,
      can also trigger carcinogenic processes. A microenvironment including active
      immune cells releasing high amounts of inflammatory signaling molecules can favor
      the carcinogenic transformation of host cells. Pivotal molecules released during
      immune response such as the macrophage migration inhibitory factor (MMIF) and the
      reactive oxygen and nitrogen species' products superoxide and peroxynitrite, can
      further damage DNA and cause the accumulation of oncogenic mutations, whereas pro
      inflammatory cytokines, adhesion molecules, and growth factors may create a
      microenvironment promoting neoplastic cell survival and proliferation. Recent
      findings on the implication of inflammatory signaling pathways in microbial
      triggered carcinogenesis as well as the possible role of microbiota modulation in
      cancer prevention are herein summarized and discussed.

PMID- 23123500
TI  - PI3K/Akt-dependent phosphorylation of GSK3beta and activation of RhoA regulate
      Wnt5a-induced gastric cancer cell migration.
AB  - Wnt5a, a non-transforming Wnt family member, plays complicated roles in
      oncogenesis and cancer metastasis. However, Wnt5a signaling in gastric cancer
      progression remains poorly defined. In this study, we found that Wnt5a dose
      dependently stimulated the migration of human gastric cancer cells (SGC-7901),
      with the maximal effect at 100 ng/mL, via enhancing phosphorylation of PI3K/Akt
      and GSK3beta and activating RhoA. Pharmaceutical inhibition of PI3K with LY294002
      or Akt siRNA significantly decreased Wnt5a-induced GSK3beta phosphorylation and
      consequently cell migration. Additionally, GSK3beta siRNA remarkably inhibited
      Wnt5a-induced RhoA activation, stress fiber formation and cell migration.
      Analogously, pre-treatment with LiCl, which induced phosphorylation of GSK3beta
      at Ser9, increased Wnt5a-induced cell migration. Finally, ectopic expression of
      dominant negative RhoA (N19) suppressed Wnt5a-induced cell migration. Taken
      together, we demonstrated for the first time that Wnt5a promoted gastric cancer
      cell migration via the PI3K/Akt/GSK3beta/RhoA signaling pathway. These findings
      could provide a rationale for designing new therapy targeting gastric cancer
      metastasis.

PMID- 23123502
TI  - Rho-kinase negatively regulates thyroid hormone-stimulated osteocalcin synthesis
      in osteoblasts.
AB  - Evidence is accumulating that Rho-associated kinase (Rho-kinase) plays important
      roles not only in vascular smooth muscle cell contraction, but also in a variety
      of cellular functions, including bone metabolism. In the present study, we
      investigated the involvement of Rho-kinase in the osteocalcin synthesis induced
      by triiodothyronine (T3) in osteoblast-like MC3T3-E1 cells. T3 time-dependently
      induced phosphorylation of myosin phosphatase targeting subunit (MYPT-1), a
      substrate of Rho-kinase. Y27632, a specific inhibitor of Rho-kinase, attenuated
      the MYPT-1 phosphorylation induced by T3. T3-stimulated osteocalcin release was
      significantly enhanced by Y27632. Fasudil, another Rho-kinase inhibitor,
      amplified the osteocalcin release induced by T3. T3-stimulated osteocalcin
      release was significantly augmented in Rho-knockdown cells with Rho A-siRNA.
      Y27632 and fasudil also increased the mRNA expression level of osteocalcin
      induced by T3. These results strongly suggest that T3 stimulates the activation
      of Rho-kinase in osteoblasts, which functions as a negative regulator of T3
      stimulated osteocalcin synthesis.

PMID- 23123503
TI  - Fibroblast growth factor 21 is induced by endoplasmic reticulum stress.
AB  - Increased hepatic expression is held responsible for elevated serum levels of
      fibroblast growth factor 21 (FGF21) in non-alcoholic fatty liver disease (NAFLD)
      but the underlying molecular mechanism is unclear. In the present study we tested
      the postulate that the metabolic hormone FGF21 is regulated by endoplasmic
      reticulum (ER) stress, a condition that is observed in a number of diseases
      including NAFLD and results in activation of an adaptive response known as the
      unfolded protein response (UPR). ER stress stimuli were found to induce
      expression of Fgf21 mRNA in H4IIE hepatoma cells and in isolated rat hepatocytes.
      Moreover, intraperitoneal injection of the ER stressor tunicamycin induced
      hepatic Fgf21 expression in mice and resulted in marked elevation of serum FGF21
      levels. The effect of ER stress on FGF21 expression could be mimicked by
      overexpression of ATF4, a transcriptional effector of the PERK-branch of the UPR.
      In silico analysis revealed the presence of two binding sites for ATF4 in the
      FGF21 promoter region. Combined disruption of these elements, abrogated FGF21
      promoter activity induced by ER stress or ATF4 overexpression. These findings
      implicate the PERK/eIF2alpha/ATF4 cascade in ER stress regulation of FGF21. A
      consequence of this notion is that other intracellular stress signaling pathways
      that converge at eIF2alpha, can regulate FGF21 expression. Indeed, both nutrient
      (amino acid deprivation) and oxidative stress (arsenite) were found to induce
      Fgf21 expression in hepatoma cells and isolated rat hepatocytes. In conclusion,
      FGF21 expression is regulated by ER stress and additional intracellular stress
      signaling pathways. Our findings suggest that increased cellular stress in fatty
      livers may underlie the elevated FGF21 levels observed in patients with NAFLD.

PMID- 23123504
TI  - Pilot study of the effect of low-cadence functional electrical stimulation
      cycling after spinal cord injury on thigh girth and strength.
AB  - OBJECTIVE: To investigate the long-term effects of functional electrical
      stimulation (FES)-evoked cycle training cadence on leg muscle hypertrophy and
      electrically evoked strength. DESIGN: Open intervention study. SETTING:
      Laboratory setting. PARTICIPANTS: Untrained individuals with chronic spinal cord
      injury (N=8). INTERVENTIONS: Six weeks (3d/wk) of training on an isokinetic FES
      cycle ergometer. For each subject, 1 leg was randomly allocated to cycling at 10
      revolutions per minute (rpm) (LOW) for 30min/d, and the other cycling at 50rpm
      (HIGH) for 30min/d. MAIN OUTCOME MEASURES: Pre- and posttraining measurements of
      lower limb circumference were performed at the distal and middle position of each
      thigh. Electrically evoked quadriceps muscle torque during an isometric
      contraction was also assessed. RESULTS: Six weeks of FES cycle training
      significantly increased thigh girth in both LOW and HIGH groups. At midthigh,
      girth increases induced by LOW (6.6%+/-1.2%) were significantly greater than
      those by HIGH (3.6%+/-0.8%). LOW also produced greater gains in electrically
      evoked isometric torque than HIGH after training. CONCLUSIONS: These results
      suggest that lower pedaling cadences evoke greater muscle hypertrophy and
      electrically stimulated muscle strength compared with higher cadences.

PMID- 23123501
TI  - Population-wide distributions of neural activity during perceptual decision
      making.
AB  - Cortical activity involves large populations of neurons, even when it is limited
      to functionally coherent areas. Electrophysiological recordings, on the other
      hand, involve comparatively small neural ensembles, even when modern-day
      techniques are used. Here we review results which have started to fill the gap
      between these two scales of inquiry, by shedding light on the statistical
      distributions of activity in large populations of cells. We put our main focus on
      data recorded in awake animals that perform simple decision-making tasks and
      consider statistical distributions of activity throughout cortex, across sensory,
      associative, and motor areas. We transversally review the complexity of these
      distributions, from distributions of firing rates and metrics of spike-train
      structure, through distributions of tuning to stimuli or actions and of choice
      signals, and finally the dynamical evolution of neural population activity and
      the distributions of (pairwise) neural interactions. This approach reveals shared
      patterns of statistical organization across cortex, including: (i) long-tailed
      distributions of activity, where quasi-silence seems to be the rule for a
      majority of neurons; that are barely distinguishable between spontaneous and
      active states; (ii) distributions of tuning parameters for sensory (and motor)
      variables, which show an extensive extrapolation and fragmentation of their
      representations in the periphery; and (iii) population-wide dynamics that reveal
      rotations of internal representations over time, whose traces can be found both
      in stimulus-driven and internally generated activity. We discuss how these
      insights are leading us away from the notion of discrete classes of cells, and
      are acting as powerful constraints on theories and models of cortical
      organization and population coding.

PMID- 23123505
TI  - Differences in tibia morphology between the sound and affected sides in ankle
      foot orthosis-using survivors of stroke.
AB  - OBJECTIVE: To examine differences in tibia and proximal femur morphology between
      the affected and sound limbs in ankle-foot orthosis (AFO)-using survivors of
      stroke. DESIGN: Observational study. SETTING: A university bone density
      laboratory. PARTICIPANTS: Ambulatory, AFO-using survivors of stroke (N=9; age
      range, 55-74y; poststroke duration, 13.5+/-4.4y; AFO use, 6.5+/-1.4y).
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Total body and hip areal
      bone mineral density (aBMD) and bone mineral content (BMC) were assessed by dual
      energy x-ray absorptiometry. The 4%, 38%, and 66% sites of both tibias were
      measured with peripheral quantitative computed tomography for total, cortical,
      and trabecular volumetric BMD (vBMD) and BMC. Bone geometry, bone strength index
      (BSI), strength strain index (SSI), and minimum and maximum rotated moments of
      inertia (Imin, Imax) were determined. RESULTS: Total hip and trochanter BMC and
      aBMD were 7% to 19% greater on the sound side (P<.05). Total BMC and vBMD were 2%
      to 21% greater (P<.05) on the sound limb, depending on site. Trabecular BMC and
      vBMD and BSI values were 19%, 21%, and 31% higher (P<.05) on the sound limb at
      the 4% site. Cortical BMC and vBMD (P<.05), and cortical thickness (P<.01) were
      greater on the sound side at the 38% and 66% sites. Cortical area and bone
      strength (SSI, Imin) were greater (P<.05) at the 66% site. Endosteal
      circumferences were greater on the affected side (P<.01). CONCLUSIONS: Interlimb
      differences in bone characteristics after a stroke persist despite returning to
      ambulatory status with AFO use.

PMID- 23123506
TI  - Racial discrimination, response to unfair treatment, and depressive symptoms
      among pregnant black and African American women in the United States.
AB  - PURPOSE: To assess the association between self-reported racial discrimination
      and prenatal depressive symptoms among black women. METHODS: Our study population
      consisted of two cohorts of pregnant women: the Asthma Coalition on Community,
      Environment, and Social Stress project (ACCESS) and Project Viva. We measured
      self-reported racial discrimination among black women using a modified
      Experiences of Discrimination scale (score 0-8). We assessed elevated depressive
      symptoms (EDS) with the Edinburgh Postnatal Depression Scale (>=13 on a 0-30
      scale). RESULTS: Fifty-four percent of ACCESS and 78% of Viva participants
      reported experiencing racial discrimination. After adjusting for age, marital
      status, income, education, and nativity, a 1-U increment in Experiences of
      Discrimination score was associated with 48% increased odds of EDS (odds ratio,
      1.48; 95% confidence interval, 1.24-1.76) for ACCESS participants but was not
      significantly associated among Viva participants (odds ratio, 1.12; 95%
      confidence interval, 0.92-1.37). In both cohorts, responding to unfair treatment
      by talking to others was associated with the lowest odds of EDS. CONCLUSIONS: Our
      findings suggest that higher levels of perceived racial discrimination may
      increase depressive symptoms during pregnancy among U.S. black women.
      Interventions involving talking to others may aid in reducing the risk of
      depressive symptoms among black women experiencing higher levels of racial
      discrimination.

PMID- 23123508
TI  - Should adjuvant radiotherapy be administered in addition to front-line aggressive
      surgery (FAS) in patients with primary retroperitoneal sarcoma?
AB  - BACKGROUND: As most patients with retroperitoneal sarcomas (RPS) die of local
      recurrence, front-line aggressive surgery (FAS) has been developed, and it seems
      to achieve better local control. The aim of this study was to evaluate conformal
      postoperative radiotherapy (PORT) in patients who had enlarged surgery. PATIENTS
      AND METHODS: Between 1994 and 2008, 110 patients with primary RPS mainly operated
      by FAS were analysed. Sixty-two patients underwent surgery and no PORT (group S),
      and 48 received surgery and PORT (group S + R). The median age was 52. Most
      patients had 3D conformal PORT (81%) with a median dose of 50 Gy. RESULTS:
      Comparing results at 5 years in the S and the S + R group, the cumulative rate of
      local failure was, respectively, 36% and 22% (NS); relapse-free survival was 47%
      and 60% (P = 0.02), and overall survival was, respectively, 77% and 71% (NS).
      CONCLUSION: Even if patients with adjuvant PORT were at higher risk of
      recurrence, there was a trend for radiotherapy (RT) to decrease the local relapse
      rate and improve recurrence-free survival. This study confirms that adjuvant
      conformal RT should be evaluated in a randomized trial, the control arm being
      FAS. Adjuvant RT in the preoperative setting is being evaluated in an EORTC
      trial.

PMID- 23123509
TI  - Safety and efficacy of weekly nab(r)-paclitaxel in combination with carboplatin
      as first-line therapy in elderly patients with advanced non-small-cell lung
      cancer.
AB  - BACKGROUND: This analysis evaluates safety and efficacy in elderly (>= 70 years
      old) versus younger patients enrolled in a phase III advanced non-small-cell lung
      cancer (NSCLC) trial. PATIENTS AND METHODS: Untreated stage IIIB/IV patients with
      PS 0/1 were randomly assigned (1:1) to carboplatin AUC6, day 1 every 3 weeks, and
      either nab-paclitaxel (Abraxane) 100 mg/m(2) weekly (nab-P/C) or solvent-based
      paclitaxel (Taxol) 200 mg/m(2) day 1 every 3 weeks (sb-P/C). The primary end
      point was overall response rate (ORR). RESULTS: Fifteen percent of 1052 enrolled
      patients were elderly: nab-P/C, n = 74; sb-P/C, n = 82. In both age cohorts, the
      ORR was higher with nab-P/C versus sb-P/C (age >= 70: 34% versus 24%, P = 0.196;
      age <70: 32% versus 25%, P = 0.013). In elderly patients, progression-free
      survival (PFS) trended in favor of nab-P/C (median 8.0 versus 6.8 months, hazard
      ratio (HR) 0.687, P = 0.134), and overall survival (OS) was significantly
      improved (median 19.9 versus 10.4 months, HR 0.583, P = 0.009). In younger
      patients, PFS (median 6.0 versus 5.8 months, HR 0.903, P = 0.256) and OS (median
      11.4 versus 11.3 months, HR 0.999, P = 0.988) were similar in both arms. Adverse
      events were similar in both age groups, with less neutropenia (P = 0.015),
      neuropathy (P = 0.001), and arthralgia (P = 0.029), and increased anemia (P =
      0.007) with nab-P/C versus sb-P/C. CONCLUSIONS: In elderly NSCLC patients, nab
      P/C as first-line therapy was well tolerated and improved the ORR and PFS, with
      substantially longer OS versus sb-PC.

PMID- 23123507
TI  - Glycemic index, glycemic load, dietary carbohydrate, and dietary fiber intake and
      risk of liver and biliary tract cancers in Western Europeans.
AB  - BACKGROUND: The type and quantity of dietary carbohydrate as quantified by
      glycemic index (GI) and glycemic load (GL), and dietary fiber may influence the
      risk of liver and biliary tract cancers, but convincing evidence is lacking.
      PATIENTS AND METHODS: The association between dietary GI/GL and carbohydrate
      intake with hepatocellular carcinoma (HCC; N = 191), intrahepatic bile duct (IBD;
      N = 66), and biliary tract (N = 236) cancer risk was investigated in 477 206
      participants of the European Prospective Investigation into Cancer and Nutrition
      cohort. Dietary intake was assessed by country-specific, validated dietary
      questionnaires. Hazard ratios and 95% confidence intervals were estimated from
      proportional hazard models. HBV/HCV status was measured in a nested case-control
      subset. RESULTS: Higher dietary GI, GL, or increased intake of total carbohydrate
      was not associated with liver or biliary tract cancer risk. For HCC, divergent
      risk estimates were observed for total sugar = 1.43 (1.17-1.74) per 50 g/day,
      total starch = 0.70 (0.55-0.90) per 50 g/day, and total dietary fiber = 0.70
      (0.52-0.93) per 10 g/day. The findings for dietary fiber were confirmed among
      HBV/HCV-free participants [0.48 (0.23-1.01)]. Similar associations were observed
      for IBD [dietary fiber = 0.59 (0.37-0.99) per 10 g/day], but not biliary tract
      cancer. CONCLUSIONS: Findings suggest that higher consumption of dietary fiber
      and lower consumption of total sugars are associated with lower HCC risk. In
      addition, high dietary fiber intake could be associated with lower IBD cancer
      risk.

PMID- 23123510
TI  - Dynamics of brain structure and cognitive function in the Alzheimer's disease
      neuroimaging initiative.
AB  - BACKGROUND: On average, cognition declines as people age, but improvement can
      also occur. OBJECTIVE: To evaluate the dynamics of age-related changes in brain
      structure and cognitive function in patients with mild Alzheimer's disease (AD)
      and mild cognitive impairment (MCI) and in healthy control (HC) older adults.
      METHODS: High-resolution 3-Tesla MRI and clinical data were obtained from the
      Alzheimer's Disease Neuroimaging Initiative in 187 subjects (a cohort aged 55-91
      years; AD=43, MCI=84, HC=60). At 24 months, 151 people had clinical and 128 had
      MRI follow-up. Brain structure was assessed using the Medial Temporal Atrophy
      Scale (MTAS) and the Brain Atrophy and Lesion Index (BALI). Cognition was
      assessed using the Mini-Mental State Examination (MMSE) and the Alzheimer Disease
      Assessment Scale-cognitive subscale (ADAS-cog). Responsiveness was tested.
      Changes were analysed using a multistate dynamic model, adjusted for age, gender,
      ApoE4 genotype and vascular risk factors. RESULTS: Over 2 years, decline in brain
      structure and cognition predominated, each showing detectable effect sizes
      (Cohen's d=0.33 for MTAS, 0.32 for BALI, 0.41 for MMSE, 0.38 for ADAS-cog;
      standard response mean=0.71, 0.69, 0.50 and 0.47, respectively). Structural
      improvement was observed (10.2% in BALI and 0.8% in MTAS), as was cognitive
      improvement (23.2% MMSE, 27.2% ADAS-cog). Most people (66.7%) whose BALI score
      improved also improved in either the MMSE or ADAS-cog. No patient with MCI whose
      MTAS or BALI improved converted to AD. CONCLUSIONS: Despite average decline in
      brain structure, improvement was observed and related to cognition and MCI-AD
      conversion. Ageing-related brain changes reflect a dynamic process.

PMID- 23123512
TI  - Direct growth of SnO2 nanowires on WOx thin films.
AB  - Single-crystalline SnO(2) nanowires were directly grown on an amorphous WO(x)
      thin film, leading to the formation of nano-scale contacts with a near-Ohmic
      conductance. The WO(x) facilitated the diffusion of SnO(2) on the surface of the
      WO(x) thin film, and SnO(2) nanowires could be uniformly grown from the diffused
      SnO(2). The contact properties between the metallic WO(x) and a semiconducting
      SnO(2) nanowire were examined. The resistivity of the WO(x)-SnO(2) nanowire
      contact was found to be approximately 2.6 * 10(-5) Omega cm(2). This was
      comparable to the resistivity of a contact between an Al electrode and a SnO(2)
      nanowire with a contact area. A fabricated SnO(2) nanowire transistor exhibited
      an on-current of approximately 386 nA, a threshold voltage of approximately 3.8
      V, a subthreshold slope of approximately 0.26 V/dec and a field-effect mobility
      of approximately 43 cm(2) V(-1) s(-1).

PMID- 23123511
TI  - The effects of age, energy and protein intake on protein turnover and the
      expression of proteolysis-related genes in the broiler breeder hen.
AB  - A study was conducted to determine the changes that occur to proteolysis and
      related genes due to age, protein, and energy intake in high-yield broiler
      breeder hens (Gallus gallus). Cobb 700 broiler breeders were randomly assigned to
      one of six diets in a 2*3 factorial fashion. Two levels of energy (390 and 450
      kcal/day) and three levels of protein (22, 24, and 26 g CP/day) were utilized.
      Protein turnover was determined in the left pectoralis at 22, 26, 31 and 44
      weeks. Relative mRNA expression of calpain 2 (CAPN2), proteasome C2 subunit
      (PSMA1), and F box protein 32 (FBXO32) were determined via RT-PCR at 20, 25, and
      44 weeks. Contrasts indicate fractional synthesis rate (FSR) and FBXO32 increase
      to a maximum at 25-26 weeks and a decrease thereafter. A significant drop in
      PSMA1 and FBXO32 was observed between 25 and 44 weeks and matched the decrease
      observed in FBR. No differences were detected in the levels of fractional
      synthesis and degradation, or the expression of CAPN2, PSMA1, and FBXO32, due to
      protein or energy intake. In summary, protein turnover was upregulated during the
      transition into sexual maturity and decreased thereafter. The observed changes in
      degradation appeared to be mediated by the ubiquitin-proteasome pathway.

PMID- 23123513
TI  - Natural variation in differentiated hemocytes is related to parasitoid resistance
      in Drosophila melanogaster.
AB  - As a measure of parasitoid resistance, hemocyte load and encapsulation ability
      were measured in lines collected from natural populations of Drosophila
      melanogaster in Europe. Results show large geographic variation in resistance
      against the parasitoid wasp Asobara tabida among the field lines, but there was
      no clear correlation between resistance and total hemocyte load, neither before
      nor after parasitization. This was in contrast to the patterns that had been
      found in a comparison among species of Drosophila, where total hemocyte counts
      were positively correlated to encapsulation rates. This suggests that the
      mechanisms underlying between-species variation in parasitoid resistance do not
      extend to the natural variation that exists within a species. Although hemocyte
      counts did not correspond to encapsulation ability within D. melanogaster, the
      ratios of lamellocytes and crystal cells were very similar in lines with
      successful encapsulation responses. Apart from variation in the hemocytic
      response of the different hemocyte types, within-species variation was also
      observed for accurate targeting of the foreign body by the hemocytes. These
      results are discussed in the context of possible causes of variation in immune
      functions among natural populations.

PMID- 23123514
TI  - Reactive oxygen species generation in fungal development and pathogenesis.
AB  - Reactive oxygen species (ROS) generated by NADPH-dependent oxidases (Nox) have
      been shown to function as signaling molecules and to be essential for many
      differentiation processes in mammals and plants. There is growing evidence that
      ROS are important for many aspects of fungal life including vegetative hyphal
      growth, differentiation of conidial anastomosis tubes, fruiting body and
      infection structure formation, and for induction of apoptosis. Recent results
      from studies in fungal saprophytic and pathogenic model systems have shed new
      light on the role of Nox in cytoskeleton organization, the structure of Nox
      complexes and links to components of the apical complex, and the localization of
      Nox to the endoplasmic reticulum.

PMID- 23123516
TI  - Exploring the entrance of proton pathways in cytochrome c oxidase from Paracoccus
      denitrificans: surface charge, buffer capacity and redox-dependent polarity
      changes at the internal surface.
AB  - Cytochrome c oxidase (CcO), the terminal oxidase of cellular respiration, reduces
      molecular oxygen to water. The mechanism of proton pumping as well as the
      coupling of proton and electron transfer is still not understood in this redox
      linked proton pump. Eleven residues at the aqueous-exposed surfaces of CcO from
      Paracoccus denitrificans have been exchanged to cysteines in a two-subunit base
      variant to yield single reactive cysteine variants. These variants are designed
      to provide unique labeling sites for probes to be used in spectroscopic
      experiments investigating the mechanism of proton pumping in CcO. To this end we
      have shown that all cysteine variants are enzymatically active. Cysteine
      positions at the negative (N-) side of the membrane are located close to the
      entrance of the D- and K-proton transfer pathways that connect the N-side with
      the catalytic oxygen reduction site. Labeling of the pH-indicator dye fluorescein
      to these sites allowed us to determine the surface potential at the cytoplasmic
      CcO surface, which corresponds to a surface charge density of -0.5 elementary
      charge/1000A(2). In addition, acid-base titrations revealed values of CcO buffer
      capacity. Polarity measurements of the label environment at the N-side provided
      (i) site-specific values indicative of a hydrophilic and a more hydrophobic
      environment dependent on the label position, and (ii) information on a global
      change to a more apolar environment upon reduction of the enzyme. Thus, the redox
      state of the copper and heme centers inside the hydrophobic interior of CcO
      affect the properties at the cytoplasmic surface.

PMID- 23123517
TI  - Mucosal immunoglobulin A in HIV-exposed seronegative individuals.

PMID- 23123515
TI  - Role of the -PEWY-glutamate in catalysis at the Q(o)-site of the Cyt bc(1)
      complex.
AB  - We re-examine the pH dependence of partial processes of ubihydroquinone (QH(2))
      turnover in Glu-295 mutants in Rhodobacter sphaeroides to clarify the mechanistic
      role. In more crippled mutants, the bell-shaped pH profile of wildtype was
      replaced by dependence on a single pK at ~8.5 favoring electron transfer. Loss of
      the pK at 6.5 reflects a change in the rate-limiting step from the first to the
      second electron transfer. Over the range of pH 6-8, no major pH dependence of
      formation of the initial reaction complex was seen, and the rates of bypass
      reactions were similar to the wildtype. Occupancy of the Q(o)-site by semiquinone
      (SQ) was similar in the wildtype and the Glu->Trp mutant. Since heme b(L) is
      initially oxidized in the latter, the bifurcated reaction can still occur,
      allowing estimation of an empirical rate constant <10(3)s(-1) for reduction of
      heme b(L) by SQ from the domain distal from heme b(L), a value 1000-fold smaller
      than that expected from distance. If the pK ~8.5 in mutant strains is due to
      deprotonation of the neutral semiquinone, with Q(*-) as electron donor to heme
      b(L), then in wildtype this low value would preclude mechanisms for normal flux
      in which semiquinone is constrained to this domain. A kinetic model in which Glu
      295 catalyzes H(+) transfer from QH*, and delivery of the H(+) to exit channel(s)
      by rotational displacement, and facilitates rapid electron transfer from SQ to
      heme b(L) by allowing Q(*-) to move closer to the heme, accounts well for the
      observations.

PMID- 23123518
TI  - Human papillomavirus vaccination:  component of an integrated HIV prevention
      program?

PMID- 23123519
TI  - Declining adherence is a more likely explanation than frailty of the apparent
      decline in efficacy in the CAPRISA 004 trial.

PMID- 23123521
TI  - The pros and cons of urinary lipoarabinomannan testing.

PMID- 23123523
TI  - The role of preparation time in the attentional blink.
AB  - This research investigated the effect of foreperiod predictability in the
      Attentional Blink (AB). The AB, a cost in processing the second of two targets
      presented in close temporal proximity, was estimated using a minimalist procedure
      consisting of two letter targets and two letter fragment masks. In a four-step
      procedure, differences in foreperiod duration, target exposure duration, and
      inter-target interval were controlled in order to estimate the AB. Foreperiod was
      manipulated in three experiments. The AB effect was reduced when a single and
      relatively long foreperiod value was used (M=880 ms, Experiment 2) in comparison
      to randomized (250-750 ms, Experiment 1) and single but relatively short
      foreperiods (M=273 ms, Experiment 3). The results are discussed in the context of
      resource-sharing and preparation of a perceptual-set pertaining to physical
      target features including modality and intensity, as well as spatial and temporal
      predictability. It is concluded that foreperiods that are too brief for an
      individual observer or temporally unpredictable contribute to the AB.

PMID- 23123525
TI  - Aspirin for venous thromboembolism prevention and treatment: a renewal?

PMID- 23123524
TI  - Role of polyadenylation in regulation of the flagella cascade and motility in
      Escherichia coli.
AB  - Polyadenylation is recognized as part of a surveillance machinery for eliminating
      defective RNA molecules in eukaryotes and prokaryotes. Escherichia coli strains,
      deficient in poly(A)polymerase I (PAP I), expressed less flagellin compared to
      wild-type strains. Because flagellin synthesis is a late step in the flagellar
      biosynthesis pathway, we assessed the role of PAP I in this cascade and in
      flagella function. Transcription of flhDC, fliA, and fliC was decreased in the
      PAP I mutant. These results provide evidence that polyadenylation positively
      controls the expression of genes belonging to the flagellar biosynthesis pathway
      and that this effect is mediated through the FlhDC master regulator. However, the
      downshift in flagella gene expression in the mutant strain did not provoke any
      noticeable defects in the synthesis of flagella, in biofilm formation and in
      swimming speed although there was a reduction in motility on soft agar. Our data
      support an alternative hypothesis that the reduced motility of the mutant
      resulted from an alteration of the cell membrane composition caused in part by
      the higher level of GlmS (Glucosamine-6P synthase) which accumulates in the
      mutant. In agreement with this hypothesis the mutant is more sensitive to
      hydrophobic agents and antibiotics and in particular to vancomycin. We propose
      that PAP I participates in the ability of the bacteria to adapt to and survive
      detrimental conditions by constantly monitoring and adjusting to its environment.

PMID- 23123526
TI  - Managing smoking cessation-related weight gain.
AB  - About 80% of smokers who stop smoking gain weight after they stop; on average 5
      kg in the first year and about 6 to 7 kg overall. However, weight gain varies a
      lot between individuals, with some putting on 10 kg or more in a year. Although
      some factors predict who will gain excessive weight, they are not clinically
      useful for targeting individuals at high risk. Instead, it may be prudent to
      monitor weight gain after cessation and intervene with people gaining more than 1
      kg/month. There is some evidence that weight gain after cessation can be
      prevented by dietary intervention that includes setting an energy intake goal and
      regular monitoring of weight and adjustment of energy intake. However, there are
      fears that such an approach may harm the success of a quit attempt because it may
      worsen craving for cigarettes. There is no evidence that this is the case, but
      the data are too imprecise to be completely reassuring. Exercise programs may
      reduce cravings for tobacco and increase the likelihood of achieving smoking
      abstinence, and there is some evidence that they reduce weight gain in the longer
      term. Consequently, they may be safely recommended but the effect on weight gain
      is modest. Long-term nicotine replacement therapy prevents several kilograms of
      weight gain but it may produce harmful metabolic changes that increase
      cardiovascular risk. Randomized trials are needed to assess efficacy. Thus,
      weight gain after cessation remains problematic with few interventions to prevent
      it that have only modest effectiveness.

PMID- 23123527
TI  - Troponin T level and mortality risk after noncardiac surgery: practical
      implications of the VISION study.
AB  - This review article presents the current state of knowledge about major
      perioperative cardiovascular complications in noncardiac surgery patients and the
      role of the currently available stratification models and biomarkers in risk
      prediction. The authors discuss a recent paper presented by the VISION
      Investigators in the June edition of the Journal of the American Medical
      Association and its practical implications in day-to-day perioperative practice.
      According to this study, the authors conclude that troponin (Tn) measurement up
      to 3 days after noncardiac surgery substantially improves perioperative risk
      estimation, and peak Tn values (even the levels previously considered as normal)
      strongly predict 30-day mortality. One in 25 patients with a peak fourth
      generation troponin T (TnT) measurement of 0.02 MUg/l, 1 in 11 patients with a
      peak TnT measurement of 0.03 to 0.29 MUg/l, and 1 in 6 patients with a peak TnT
      measurement of 0.30 MUg/l or higher will die within 30 days of surgery.
      Postoperative monitoring of TnT measurements substantially improves risk
      stratification after noncardiac surgery and may help identify patients requiring
      further therapeutic interventions.

PMID- 23123528
TI  - Iron metabolism in solid-organ transplantation: how far are we from solving the
      mystery?
AB  - Iron is the most abundant transition metal in the human body and an essential
      element required for growth and survival. Our understanding of the molecular
      control of iron metabolism has increased dramatically over the past 10 years due
      to the discovery of hepcidin, which regulates the uptake of dietary iron and its
      mobilization from macrophages and hepatic stores. Although general practitioners
      and internists encounter iron deficiency and anemia in their everyday practice,
      little is known about iron metabolism in patients after solid-organ
      transplantation. The aim of this review was to summarize the current knowledge on
      iron metabolism in kidney, heart, and liver transplant recipients. Iron
      deficiency and/or anemia, as well as iron overload, are frequently observed but
      the precise mechanism of these disturbances have not been fully elucidated. Iron
      deficiency is more prevalent in kidney and heart transplant patients, while iron
      overload in liver transplant recipients. Secondary and potentially reversible
      causes of these disturbances should be considered such as inflammation, graft
      failure, and type of immunosuppression. Iron status check-up should be a part of
      long term follow-up because disturbances in iron metabolism are a possible risk
      factor of infections and mortality in solid transplant recipients. Internists and
      general practitioners are often the first doctors to take care of organ
      transplant recipients (before they will present at outpatient transplant clinics
      or hospital transplant units); therefore, knowledge about the disturbances in
      iron metabolism in this specific population would be useful for better diagnosis
      and treatment both before and after transplantation.

PMID- 23123529
TI  - Time for reflection on patient's safety in healthcare.

PMID- 23123530
TI  - Modulation of serum levels of sRAGE by bromelain in patients with chronic kidney
      disease: a pilot study.

PMID- 23123532
TI  - Gauging rheumatoid arthritis.

PMID- 23123531
TI  - Hybrid cognitive-behaviour therapy for individuals with insomnia and chronic
      pain: a pilot randomised controlled trial.
AB  - OBJECTIVE: Insomnia is a debilitating comorbidity of chronic pain. This pilot
      trial tested the utility of a hybrid treatment that simultaneously targets
      insomnia and pain-related interference. METHODS: Chronic pain patients with
      clinical insomnia were randomly allocated to receive 4 weekly 2-h sessions of
      hybrid treatment (Hybrid Group; n = 10) or to keep a pain and sleep diary for 4
      weeks, before receiving the hybrid treatment (Monitoring Group; n = 10).
      Participants were assessed at the beginning and end of this 4-week period.
      Primary outcomes were insomnia severity and pain interference. Secondary outcomes
      were fatigue, anxiety, depression and pain intensity. Ancillary information about
      the hybrid treatment's effect on psychological processes and sleep (as measured
      with sleep diary and actigraphy) are also presented, alongside data demonstrating
      the treatment's clinical significance, acceptability and durability after one and
      six months. Data from all participants (n = 20) were combined for this purpose.
      RESULTS: Compared to symptom monitoring, the hybrid intervention was associated
      with greater improvement in sleep (as measured with the Insomnia Severity Index
      and sleep diary) at post-treatment. Although pain intensity did not change, the
      Hybrid Group reported greater reductions in pain interference, fatigue and
      depression than the Monitoring Group. Overall, changes associated with the hybrid
      intervention were clinically significant and durable at 1- and 6-month follow
      ups. Participants also rated highly on treatment acceptability. CONCLUSION: The
      hybrid intervention appeared to be an effective treatment for chronic pain
      patients with insomnia. It may be a treatment approach more suited to tackle
      challenges presented in clinical practice, where problems seldom occur in
      isolation.

PMID- 23123533
TI  - New biomarkers in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a common autoimmune disease affecting around 1% of
      the population. Although major advances have been made in the treatment of RA,
      still relatively little is known on disease pathogenesis and aetiology. From
      treatment studies it has become clear that treating patients early in their
      disease course will provide the best results. However, especially in the early
      phase of arthritis, in particular when the patients do not yet fulfil the
      criteria for RA, it is difficult to decide which patients would benefit most from
      an early and aggressive intervention. Good biomarkers are important to guide
      decisions in the clinical management of RA. Next to the well-known rheumatoid
      factor (RF) and the anti-citrullinated protein antibodies (ACPA), several new
      markers are now likely to become available with interesting potential. Besides
      antibody responses directed against citrullinated proteins, also antibodies
      against carbamylated proteins (anti-CarP) have recently been shown to be present
      in RA. Interestingly these anti-CarP antibodies are also present in around 20% of
      the ACPA-negative RA patients and are associated with more severe joint damage in
      this group. Apart from the antibodies that help in establishing the diagnosis and
      prognosis, also novel biomarkers that reflect clinical disease activity scores
      are being discovered. The development of biomarker-based disease activity scores
      might allow easy and frequent monitoring of patients to rapidly adjust treatment.

PMID- 23123534
TI  - Prothrombotic disorders in abdominal vein thrombosis.
AB  - Abdominal vein thrombosis is a rare, but potentially life-threatening form of
      venous thrombosis. It mainly involves the hepatic veins (Budd Chiari syndrome,
      BCS), portal veins (PVT) and mesenteric veins. In recent years several large
      scale studies have been performed to study the underlying aetiological factors in
      these thrombotic disorders. Both inherited and acquired thrombophilia factors are
      frequently observed in these patients. Factor V Leiden mutation is frequently
      found in patients with BCS and prothrombin gene variant is seen more frequently
      in PVT. Myeloproliferative neoplasms (MPNs), including polycythemia vera and
      essential thrombocythemia, are underlying disorders in 30-40% of patients with
      abdominal vein thrombosis. Other aetiological factors are paroxysmal nocturnal
      haemoglobinuria (PNH), autoimmune disorders and hormonal factors. Recently,
      several new risk factors have been reported and are discussed in this review. BCS
      and PVT are multi-factorial disorders. In nearly 50% of patients two, and in 16%
      even three prothrombotic risk factors were found at presentation. Because
      patients with abdominal vein thrombosis have a high risk of recurrence immediate
      anticoagulant treatment is necessary. The duration of treatment is still a matter
      of debate because these patients also have a high risk of bleeding, especially
      those with portal hypertension. For BCS patients life-long anticoagulant
      treatment is advised. In patients with PVT it is recommended to tailor treatment
      to the individual patient based on the presence of an underlying prothrombotic
      disorder and the risk of bleeding.

PMID- 23123535
TI  - Protocolised inpatient care of diabetes mellitus.
AB  - BACKGROUND: The prevalence of hyperglycaemia in patients with diabetes mellitus
      at admission is high. Prevention and treatment is important to prevent further
      clinical complications. We have conducted a study evaluating implementation of a
      new protocol to standardise inpatient care of patients with diabetes mellitus.
      METHODS: A retrospective study including all glucose measurements of adult
      patients with diabetes mellitus type 1 o r 2 , admitted to a surgery department,
      was performed before and after implementation of the new protocol. This protocol
      included direct consultation of an internist and diabetes specialist nurse at
      admission, who initiated a daily treatment program and adjustment scheme based on
      glucose measurements four times a day by the HemoCue201DM glucose point of care
      device. We compared the prevalence of hyperglycaemia and hypoglycaemia before and
      after implementation with logistic regression analyses adjusted for age and
      gender. RESULTS: Overall, 360 patients with diabetes mellitus type 1 or 2 with
      5322 glucose measurements were included. The risk of developing hyperglycaemia
      was significantly reduced after implementation of the protocol (22 patients with
      65 hyperglycaemias) compared with before the intervention (70 patients with 417
      hyperglycaemias) (RR adjusted 0.24 (95% confidence interval 0.19; 0.32)).
      Overall, 45 patients experienced 95 episodes of hypoglycaemia, which did not
      differ significantly between the two groups. CONCLUSION: After implementation of
      a new protocol to standardise inpatient care of diabetes mellitus we established
      a decrease in the risk to develop hyperglycaemia of 76% without an increased risk
      of developing hypoglycaemia. Implementation of this protocol required frequent
      glucose measurements which are facilitated by point of care glucose measurements.

PMID- 23123536
TI  - Waldenstrom's macroglobulinaemia presenting with nephrotic syndrome.

PMID- 23123537
TI  - A case of painless jaundice.

PMID- 23123538
TI  - Rapid widening of the mediastinum after coronary angiography.

PMID- 23123539
TI  - A longstanding non-painful tumour of the back.

PMID- 23123540
TI  - Floppy ears and tracheal wall narrowing.

PMID- 23123541
TI  - Life-threatening complications of ibogaine: three case reports.
AB  - Ibogaine is a naturally occurring psychoactive alkaloid extracted from the roots
      of the Tabernanthe iboga plant, which in alternative medicine is used to treat
      drug dependency. However, this upcoming, online advocated therapy can be
      dangerous due to its potentially lethal adverse effects. We present three cases
      in which toxic side effects were noted. We used the Naranjo scale to estimate the
      probability of a causal relationship between these effects and ibogaine. Findings
      in these three cases are suggestive of a causal relationship between the use of
      ibogaine and serious respiratory and cardiac problems (including lengthening of
      the QT interval). In our opinion it is of great importance that clinicians are
      aware of these potentially serious side effects and realise that widespread
      online marketing practices will give many more people access to ibogaine.

PMID- 23123542
TI  - Approach to hypophosphataemia in intensive care units - a nationwide survey.
AB  - BACKGROUND: Evidence-based guidelines for monitoring of serum phosphate levels
      and for the treatment of hypophosphataemia in critically ill patients are
      lacking. The aim of this survey was to evaluate current practice with respect to
      diagnosis and treatment of hypophosphataemia in critically ill patients among
      intensive care unit (ICU) physicians in the Netherlands. METHODS: A survey was
      conducted among all hospitals with an ICU in the Netherlands. Paediatric ICUs
      were excluded from participation. A questionnaire was sent, with questions on
      practice regarding serum phosphate monitoring and treatment of hypophosphataemia.
      Respondents returned the questionnaire either by mail or through a web-based
      survey. RESULTS: A response was received from 67/89 ICUs (75%). Respondents
      mentioned renal replacement therapy, sepsis and malnutrition, as well as surgery
      involving cardiopulmonary bypass as the most important causes of
      hypophosphataemia in intensive care unit patients. Of all respondents, 46%
      reported to measure serum phosphate levels on a daily basis, whereas in 12% serum
      phosphate levels were measured only on clinical indication. Less than half of the
      respondents had some sort of guideline for correction of hypophosphataemia. In a
      vast majority (79%), correction of hypophosphataemia was reported to start with
      serum phosphate levels.

PMID- 23123543
TI  - Hypertension and use of an intrauterine levonorgestrel-releasing device.

PMID- 23123544
TI  - Gag-CA Q110D mutation elicits TRIM5-independent enhancement of HIV-1mt
      replication in macaque cells.
AB  - HIV-1 is strictly adapted to humans, and cause disease-inducing persistent
      infection only in humans. We have generated a series of macaque-tropic HIV-1 (HIV
      1mt) to establish non-human primate models for basic and clinical studies. HIV
      1mt clones available to date grow poorly in macaque cells relative to SIVmac239.
      In this study, viral adaptive mutation in macaque cells, G114E in capsid (CA)
      helix 6 of HIV-1mt, that enhances viral replication was identified. Computer
      assisted structural analysis predicted that another Q110D mutation in CA helix 6
      would also increase viral growth potential. A new proviral construct MN4Rh-3
      carrying CA-Q110D exhibited exquisitely enhanced growth property specifically in
      macaque cells. Susceptibility of MN4Rh-3 to macaque TRIM5alpha/TRIMCyp proteins
      was examined by their expression systems. HIV-1mt clones so far constructed
      already completely evaded TRIMCyp restriction, and further enhancement of TRIMCyp
      resistance by Q110D was not observed. In addition, Q110D did not contribute to
      evasion from TRIM5alpha restriction. However, the single-cycle infectivity of
      MN4Rh-3 in macaque cells was enhanced relative to the other HIV-1mt clones. Our
      results here indicate that CA-Q110D accelerates viral growth in macaque cells
      irrelevant to TRIM5 proteins restriction.

PMID- 23123545
TI  - Re: diagnostic radiation exposure risk in a contemporary cohort of male patients
      with germ cell tumor.

PMID- 23123546
TI  - Response to Comments: Diagnostic Radiation Exposure Risk in A Contemporary Cohort
      of Male Patients with Germ Cell Tumor.

PMID- 23123547
TI  - Pooled analysis of clinical outcomes with neoadjuvant cisplatin and gemcitabine
      chemotherapy for muscle invasive bladder cancer.
AB  - PURPOSE: Neoadjuvant chemotherapy for muscle invasive bladder cancer has been
      shown to confer a survival advantage in phase III studies. Although cisplatin and
      gemcitabine are often used in this setting, a comprehensive evaluation of this
      regimen is lacking. In this review we summarize the efficacy of neoadjuvant
      cisplatin and gemcitabine chemotherapy for muscle invasive bladder cancer based
      on currently published studies. MATERIALS AND METHODS: A systematic literature
      review was conducted in April 2012 searching MEDLINE(r) databases. Articles were
      selected if they included patients with muscle invasive bladder cancer, evaluated
      the combination of cisplatin and gemcitabine as neoadjuvant treatment, and
      reported pathological data after cystectomy. Cisplatin and gemcitabine dosing
      regimens and clinical data were further summarized using weighted averages.
      RESULTS: Seven studies encompassing 164 patients were published between 2007 and
      2012. The majority of patients (79%) received cisplatin and gemcitabine on a 21
      day cycle. A weighted average of 19.2 lymph nodes was obtained at cystectomy, and
      29.7% of patients were found to have pN1 disease. Pathological down staging to
      pT0 and less than pT2 occurred in 42 (25.6%) and 67 (46.5%) patients,
      respectively. CONCLUSIONS: Neoadjuvant cisplatin and gemcitabine yield
      appreciable pathological response rates in patients with muscle invasive bladder
      cancer. Since pathological response has been implicated as a potential surrogate
      for survival in muscle invasive bladder cancer, these data suggest that
      neoadjuvant cisplatin and gemcitabine may warrant further prospective assessment.

PMID- 23123548
TI  - Surgeon variation in patient quality of life after radical prostatectomy.
AB  - PURPOSE: We assessed variation among surgeons in patient quality of life
      outcomes. MATERIALS AND METHODS: A survey of standard questions used to examine
      current urinary and sexual function was mailed to 1,500 randomly selected
      patients from the Utah Cancer Registry who met certain criteria, including
      prostatectomy for cancer cure more than 1 year previously, current age 70 years
      or less and no metastatic disease or other cancer therapy. Questionnaire
      information was linked to cancer registry and hospital discharge abstract
      information. Hierarchical mixed models were used to examine whether surgeons
      varied with respect to risk adjusted outcomes. RESULTS: The cooperation rate was
      64%. Of the 678 qualifying responders 22% reported leaking urine more than once
      per day, 7% used more than 1 pad per day and 40% reported no erection without
      medication. Surgeon variation was significant for 3 patient outcomes, including
      erectile strength, urine leakage and length of hospital stay (each p <0.001).
      Surgeon risk adjusted erectile outcomes significantly correlated with leakage
      outcomes (r = 0.84, p <0.0001) and length of stay (r = -0.55, p = 0.0004). Annual
      surgeon volume significantly correlated with less leakage and shorter length of
      stay (r = 0.34 and -0.36, respectively, each p = 0.05). Compared to open
      retropubic surgery, robotic surgery was associated with a shorter stay. The
      perineal approach was associated with shorter stay, less urine leakage and weaker
      erection. CONCLUSIONS: Patient quality of life outcomes after prostatectomy
      varies substantially among surgeons. Administering patient surveys through cancer
      registries may provide valuable data for improving prostatectomy outcomes
      statewide.

PMID- 23123549
TI  - Electrosurgical enucleation versus bipolar transurethral resection for prostates
      larger than 70 ml: a prospective, randomized trial with 5-year followup.
AB  - PURPOSE: We compared the perioperative and postoperative characteristics of
      prostate PlasmaKineticTM enucleation and bipolar transurethral resection for
      large volume benign prostatic hyperplasia. MATERIALS AND METHODS: In this
      prospective, randomized, controlled trial 80 patients with benign prostatic
      hyperplasia and a prostate of larger than 70 ml were randomly assigned to
      prostate bipolar transurethral resection or PlasmaKinetic enucleation. Operative
      time, resected adenoma weight, changes in hemoglobin, catheterization time and
      postoperative hospital stay were recorded and compared. Patients were followed 1,
      6, 12, 24, 36, 48 and 60 months after surgery. RESULTS: Greater resected prostate
      weight (mean +/- SD 64.2 +/- 19.0 vs 50.6 +/- 20.0 gm, p = 0.03), less blood loss
      (mean 0.87 +/- 0.42 vs 1.74 +/- 0.63 gm, p <0.01), and shorter catheterization
      time (mean 35.5 +/- 5.8 vs 60.1 +/- 5.8 hours, p <0.01) and postoperative
      hospital stay (mean 3 vs 4 days, [corrected] p <0.01) were recorded in the
      enucleation group than in the resection group. The postoperative improvement in
      International Prostate Symptom Score, quality of life, maximal flow rate and post
      void residual urine volume was similar in the 2 groups at 1, 6, 12 and 24 months
      but significantly better in the enucleation group at 36, 48 and 60 months. During
      the 5-year followup no patient in the enucleation group but 2 in the resection
      group experienced recurrence. CONCLUSIONS: For large volume benign prostatic
      hyperplasia PlasmaKinetic enucleation of the prostate is associated with less
      blood loss, shorter hospital stay and catheterization time than bipolar
      transurethral resection of the prostate. Moreover, PlasmaKinetic enucleation
      seems to be superior at long-term followup with fewer reoperations necessary.

PMID- 23123550
TI  - Acetohydroxyacid synthase (AHAS) in vivo assay for screening imidazolinone
      resistance in sunflower (Helianthus annuus L.).
AB  - The objective of this work was to evaluate the in vivo acetohydroxyacid synthase
      (AHAS) activity response to imidazolinones and its possible use as a selection
      method for evaluating AHAS inhibitor resistance. In vivo AHAS assay and the
      comparison of parameters from dose-response curves have been used as a valid tool
      for comparing sunflower lines and hybrids differing in imidazolinone resistance.
      The sunflower resistant genotypes evaluated here were 100-fold and 20-fold more
      resistant compared with the susceptible line for imazethapyr and imazapyr,
      respectively. This assay also allowed discrimination of homozygous from
      heterozygous genotypes for I(mr1) locus that codify for the catalytic subunit of
      AHAS. The in vivo AHAS assay described in this study was useful for the selection
      of sunflower genotypes differing in herbicide resistance and could be a useful
      tool when breeding for imidazolinone resistance in sunflower.

PMID- 23123552
TI  - Percutaneous coronary intervention vs. coronary artery bypass graft surgery for
      unprotected left main coronary artery disease in the drug-eluting stents era--an
      aggregate data meta-analysis of 11,148 patients.
AB  - BACKGROUND: Patients with unprotected left main coronary artery (LMCA) disease
      are increasingly treated with percutaneous coronary intervention (PCI) using drug
      eluting stents (DES), but its benefits compared with coronary artery bypass
      grafting (CABG) remain controversial. We hypothesized that PCI with DES for
      unprotected LMCA disease is safe and effective compared with CABG. METHODS AND
      RESULTS: We performed aggregate data meta-analyses of clinical outcomes [death;
      non-fatal myocardial infarction (MI); stroke; repeat revascularization; and major
      adverse cardiac and cerebrovascular events (MACCE)] in studies comparing PCI with
      DES vs. CABG in patients with LMCA disease. A comprehensive literature search
      (01/01/2003 to 12/01/2011) identified 27 studies comparing PCI and CABG (11,148
      patients). Summary odds ratios (OR) were calculated using a random-effects model.
      At 30 days, PCI for unprotected LMCA disease was associated with lower MACCE
      [odds ratio (OR) 0.57, 95% confidence interval (CI) 0.36-0.89) and stroke rates
      (OR 0.22, 95% CI 0.11-0.44) compared with CABG. At 12 months, the PCI group
      experienced higher rates of repeat revascularization (OR 3.72, 95% CI 2.75-5.03),
      but lower rates of stroke (OR 0.25, 95% CI 0.14-0.44) and all-cause death (OR
      0.69, 95% CI 0.49-0.97). At the longest follow-up of 60 months, PCI was
      associated with equivalent mortality, lower rates of stroke (OR 0.42, 95% CI 0.28
      0.62) and higher rates of MACCE (OR 1.30, 95% CI 1.10-1.55) and repeat
      revascularization (OR 3.54, 95% CI 2.75-4.54). CONCLUSIONS: In the DES era, PCI
      for unprotected LMCA disease is associated with equivalent mortality and MI,
      lower stroke rates and higher rates of repeat revascularization compared with
      CABG.

PMID- 23123553
TI  - Triggers for surgical referral in degenerative mitral valve regurgitation.
AB  - Degenerative mitral valve disease is the most common etiology of mitral
      regurgitation in developed countries. Degenerative mitral valve disease should be
      distinguished from other valvular disease because most of the lesions caused by
      degenerative changes are amenable to valve repair as opposed to replacement, and
      successful durable repair with optimal timing can maintain the patient's normal
      life expectancy. Despite dramatic surgical progress in degenerative mitral valve
      repair over the past few decades and detailing of surgical indications in
      established practice guidelines, prevailing data suggest a significant number of
      patients are still not referred for surgery in a timely fashion or are even
      denied for surgery for inappropriate reasons. This article reviews the current
      surgical triggers which all practicing cardiovascular specialists should be
      familiar with and which should prompt immediate surgical referral.

PMID- 23123554
TI  - Renal tubulointerstitial damage is associated with short-term cardiovascular
      events in patients with myocardial infarction.
AB  - BACKGROUND: Urinary beta2 microglobulin (U-beta2MG) is a more sensitive and
      accurate marker of tubulointerstitial damage. The etiology of glomerular damage
      is related to the occurrence of major adverse cardiovascular events (MACE) in
      patients with myocardial infarction (MI); however, the prognostic importance of
      tubulointerstitial damage in patients with ST-segment elevation MI (STEMI) has
      not been established. The aim of this study was to elucidate whether renal
      tubulointerstitial damage is associated with the occurrence of MACE in patients
      after STEMI undergoing percutaneous coronary intervention. METHODS AND RESULTS:
      The degree of renal tubulointerstitial damage was evaluated by measuring the U
      beta2MG level in 89 consecutive STEMI patients. There were 22 MACEs during the
      follow-up period. Patients with MACE had higher U-beta2MG levels than those
      without MACE, and the U-beta2MG level was an independent predictor for MACE. A
      Kaplan-Meier analysis revealed that the group with higher U-beta2MG levels
      corrected for urinary creatinine was associated with a greater risk for MACE.
      CONCLUSIONS: An elevated U-beta2MG level was associated with the occurrence of
      MACE in STEMI patients who underwent PCI. Renal tubulointerstitial damage is
      therefore considered to be associated with the occurrence of MACE.

PMID- 23123556
TI  - Design and analysis of metabolic pathways supporting formatotrophic growth for
      electricity-dependent cultivation of microbes.
AB  - Electrosynthesis is a promising approach that enables the biological production
      of commodities, like fuels and fine chemicals, using renewably produced
      electricity. Several techniques have been proposed to mediate the transfer of
      electrons from the cathode to living cells. Of these, the electroproduction of
      formate as a mediator seems especially promising: formate is readily soluble, of
      low toxicity and can be produced at relatively high efficiency and at reasonable
      current density. While organisms that are capable of formatotrophic growth, i.e.
      growth on formate, exist naturally, they are generally less suitable for bulk
      cultivation and industrial needs. Hence, it may be helpful to engineer a model
      organism of industrial relevance, such as E. coli, for growth on formate. There
      are numerous metabolic pathways that can potentially support formatotrophic
      growth. Here we analyze these diverse pathways according to various criteria
      including biomass yield, thermodynamic favorability, chemical motive force,
      kinetics and the practical challenges posed by their expression. We find that the
      reductive glycine pathway, composed of the tetrahydrofolate system, the glycine
      cleavage system, serine hydroxymethyltransferase and serine deaminase, is a
      promising candidate to support electrosynthesis in E. coli. The approach
      presented here exemplifies how combining different computational approaches into
      a systematic analysis methodology provides assistance in redesigning metabolism.
      This article is part of a Special Issue entitled: Metals in Bioenergetics and
      Biomimetics Systems. 

PMID- 23123557
TI  - Indirect reciprocity with trinary reputations.
AB  - Indirect reciprocity is a reputation-based mechanism for cooperation in social
      dilemma situations when individuals do not repeatedly meet. The conditions under
      which cooperation based on indirect reciprocity occurs have been examined in
      great details. Most previous theoretical analysis assumed for mathematical
      tractability that an individual possesses a binary reputation value, i.e., good
      or bad, which depends on their past actions and other factors. However, in real
      situations, reputations of individuals may be multiple valued. Another puzzling
      discrepancy between the theory and experiments is the status of the so-called
      image scoring, in which cooperation and defection are judged to be good and bad,
      respectively, independent of other factors. Such an assessment rule is found in
      behavioral experiments, whereas it is known to be unstable in theory. In the
      present study, we fill both gaps by analyzing a trinary reputation model. By an
      exhaustive search, we identify all the cooperative and stable equilibria composed
      of a homogeneous population or a heterogeneous population containing two types of
      players. Some results derived for the trinary reputation model are direct
      extensions of those for the binary model. However, we find that the trinary model
      allows cooperation under image scoring under some mild conditions.

PMID- 23123555
TI  - Offense and defense: microbial membrane vesicles play both ways.
AB  - Microbes have evolved over millennia to become adapted and specialized to the
      environments that they occupy. These environments may include water or soil,
      extreme environments such as hydrothermal vents, and can even include a host
      organism. To become adapted to these locations, microbes have evolved specific
      tools to mediate interactions with the environment. One such tool that
      prokaryotes have evolved includes the production of membrane vesicles (MVs). MVs
      are 10-300 nm spherical blebs derived from the outermost membrane and have known
      functions in protein secretion, immune activation and suppression, stress
      response, attachment, internalization and virulence. In this review, we consider
      the highly conserved role of membrane vesicles derived from Gram-negative, Gram
      positive and archaeal species as a mechanism to facilitate intermicrobial and
      microbe-host interaction. We examine both the offensive and defensive
      capabilities of MVs in regard to the interaction of MVs with both host and
      microbial cells in their environment.

PMID- 23123558
TI  - The optimal timing of initiation of therapeutic hypothermia after cardiac arrest.

PMID- 23123559
TI  - Resuscitation of avalanche victims: Evidence-based guidelines of the
      international commission for mountain emergency medicine (ICAR MEDCOM): intended
      for physicians and other advanced life support personnel.
AB  - BACKGROUND: In North America and Europe ~150 persons are killed by avalanches
      every year. METHODS: The International Commission for Mountain Emergency Medicine
      (ICAR MEDCOM) systematically developed evidence-based guidelines and an algorithm
      for the management of avalanche victims using a worksheet of 27 Population
      Intervention Comparator Outcome questions. Classification of recommendations and
      level of evidence are ranked using the American Heart Association system. RESULTS
      AND CONCLUSIONS: If lethal injuries are excluded and the body is not frozen, the
      rescue strategy is governed by the duration of snow burial and, if not available,
      by the victim's core-temperature. If burial time <=35 min (or core-temperature
      >=32  degrees C) rapid extrication and standard ALS is important. If burial time
      >35 min and core-temperature <32  degrees C, treatment of hypothermia including
      gentle extrication, full body insulation, ECG and core-temperature monitoring is
      recommended, and advanced airway management if appropriate. Unresponsive patients
      presenting with vital signs should be transported to a hospital capable of active
      external and minimally invasive rewarming such as forced air rewarming. Patients
      with cardiac instability or in cardiac arrest (with a patent airway) should be
      transported to a hospital for extracorporeal membrane oxygenation or
      cardiopulmonary bypass rewarming. Patients in cardiac arrest should receive
      uninterrupted CPR; with asystole, CPR may be terminated (or withheld) if a
      patient is lethally injured or completely frozen, the airway is blocked and
      duration of burial >35 min, serum potassium >12 mmol L(-1), risk to the rescuers
      is unacceptably high or a valid do-not-resuscitate order exists. Management
      should include spinal precautions and other trauma care as indicated.

PMID- 23123560
TI  - Letter: Is early hypothermia deleterious in comatose survivors to cardiac arrest?

PMID- 23123561
TI  - Adiponectin levels and risk of coronary heart disease: a meta-analysis of
      prospective studies.
AB  - BACKGROUND: Adiponectin is the most abundant circulating protein secreted by
      adipocytes. There is uncertainty about the association between adiponectin levels
      and risk of coronary heart disease (CHD). We conducted this meta-analysis to
      summarize the effect of adiponectin on the risk of CHD. METHODS: A comprehensive
      search was performed to identify all prospective studies on the association of
      adiponectin levels and risk of CHD. The quality of the eligible studies was
      evaluated by the Newcastle-Ottawa Scale. The fixed- or random-effects model was
      selected to pool the relative risk (RR) and 95% confidence interval (CI).
      Heterogeneity among studies was evaluated using Q test and the I2 statistic.
      Publication bias was estimated using modified Egger's linear regression test.
      RESULTS: Twelve prospective studies comprising 8 nested case-control studies and
      4 cohort studies were included in the meta-analysis. A total of 14,960
      participants were enrolled and 4,132 incident CHD events were observed. The
      pooled RR for CHD was 0.83 (95% CI, 0.69-0.98, P = 0.031). Subgroup analyses
      showed that the pooled RRs (95% CIs) for CHD risk were 0.78 (0.66-0.92) and 0.75
      (0.59-0.94) for men and women, respectively. For studies with mean age less than
      65 years, the pooled RR (95% CI) for CHD risk was 0.72 (0.59-0.87). For studies
      with 100 or more CHD cases, the pooled RR was marginally significant (RR = 0.83,
      95% CI, 0.69-1.00; P = 0.051). No publication bias was found in our study (P =
      0.911). CONCLUSIONS: This meta-analysis showed that higher levels of adiponectin
      were associated with a low risk of CHD. The protective effect was consistently
      existed in men and women and in the middle-aged populations.

PMID- 23123562
TI  - The 4 humors and erythrocyte sedimentation: the most influential observation in
      medical history.

PMID- 23123563
TI  - Cauliflower bowel: a tumor-induced mesenteric retraction.

PMID- 23123564
TI  - Vasoactive intestinal peptide induces oxidative stress and suppresses metastatic
      potential in human clear cell renal cell carcinoma.
AB  - Molecular mechanisms involved in progression of clear-cell renal-cell carcinomas
      (ccRCCs) are poorly understood. A common genetic mutation found in ccRCC is the
      loss of the von Hippel-Lindau (VHL) gene, which contributes to cancer progression
      and metastasis. We investigated VIP effects on metastatic and angiogenic factors
      in human VHL-null A498 ccRCC and HK2 renal cells. VIP increased adhesion but
      decreased expression of metalloproteinases, MMP2 and MMP9, as well as cell
      migration and VEGF expression and secretion in A498 but not in HK2 cells. VIP
      enhanced ROS levels and decreased nuclear levels of beta-catenin and NFkappaB p50
      subunit in A498 cells, suggesting neuropeptide involvement in the observed
      decrease of metastatic ability in clear-cell carcinoma. VIP effects in A498 cells
      were blocked by the VPAC(1/2)-receptor antagonist JV-1-53. In conclusion, present
      data point to a role of VIP in preventing invasion and metastasis in ccRCCs and
      support its potential therapeutic usefulness in this disease.

PMID- 23123565
TI  - Peptide-induced bilayer thinning structure of unilamellar vesicles and the
      related binding behavior as revealed by X-ray scattering.
AB  - We have studied the bilayer thinning structure of unilamellar vesicles (ULV) of a
      phospholipid 1,2-dierucoyl-sn-glycero-3-phosphocholine (di22:1PC) upon binding of
      melittin, a water-soluble amphipathic peptide. Successive thinning of the ULV
      bilayers with increasing peptide concentration was monitored via small-angle X
      ray scattering (SAXS). Results suggest that the two leaflets of the ULV of closed
      bilayers are perturbed and thinned asymmetrically upon free peptide binding, in
      contrast to the centro-symmetric bilayer thinning of the substrate-oriented
      multilamellar membranes (MLM) with premixed melittin. Moreover, thinning of the
      melittin-ULV bilayer associates closely with peptide concentration in solution
      and saturates at ~4%, compared to the ~8% maximum thinning observed for the
      correspondingly premixed peptide-MLM bilayers. Linearly scaling the thinning of
      peptide-ULV bilayers to that of the corresponding peptide-MLM of a calibrated
      peptide-to-lipid ratio, we have deduced the number of bound peptides on the ULV
      bilayers as a function of free peptide concentration in solution. The hence
      derived X-ray-based binding isotherm allows extraction of a low binding constant
      of melittin to the ULV bilayers, on the basis of surface partition equilibrium
      and the Gouy-Chapman theory. Moreover, we show that the ULV and MLM bilayers of
      di22:1PC share a same thinning constant upon binding of a hydrophobic peptide
      alamethicin; this result supports the linear scaling approach used in the
      melittin-ULV bilayer thinning for thermodynamic binding parameters of water
      soluble peptides.

PMID- 23123566
TI  - Phospholipidomics reveals differences in glycerophosphoserine profiles of
      hypothermically stored red blood cells and microvesicles.
AB  - During their normal in vivo life cycle erythrocytes (red blood cells, RBCs)
      undergo biochemical changes leading to membrane microvesiculation and shedding.
      RBC microvesiculation also occurs in vitro under conditions of blood bank
      storage, so microvesicles (MVs) accumulate in the storage (preservation) medium
      over storage time. Considerable effort has been put into gaining a mechanistic
      understanding of the RBC microvesiculation process, as this is crucial to better
      understand RBC biology in disease and in health. Additionally, MVs accumulated in
      stored RBCs have been implicated in transfusion adverse inflammatory reactions,
      with chloroform extractable compounds, thus lipophilic, known to trigger the
      effect. However, because thin layer chromatography resolution of RBC and MV
      lipids has always enabled one to conclude high compositional similarities, in
      depth analysis of MV lipids has not been extensively pursued. Here we present an
      orbitrap mass spectrometry (MS) approach to compare the phospholipid composition
      of RBCs and MVs from leukoreduced, hypothermically (2-6 degrees C) stored RBC
      units. We used shotgun MS analysis and electrospray ionization (ESI) intra-source
      separation, and demonstrated high similarity of compositional profiles, except
      for glycerophosphoserines (PS). Contrasting abundances of PS 38:4 and PS 38:1
      characterized MV and RBC profiles and suggested that storage-associated
      microvesiculation possibly involves shedding of specific membrane rafts. This
      finding indicates that phospholipidomics could likely contribute to a better
      understanding of the RBC microvesiculation process.

PMID- 23123568
TI  - A meta-analytic review of exposure in group cognitive behavioral therapy for
      posttraumatic stress disorder.
AB  - Although the efficacy of exposure is well established in individual cognitive
      behavioral treatments for posttraumatic stress disorder (PTSD), some clinicians
      and researchers have expressed concerns regarding the use of in-session
      disclosure of trauma details through imaginal exposure in group cognitive
      behavioral therapy (GCBT) for PTSD. Thus, the aim of the present study was to
      conduct a systematic review of the empirical support for GCBT in the treatment of
      PTSD and to compare GCBT protocols that encourage the disclosure of trauma
      details via in-session exposure to GCBT protocols that do not include in-session
      exposure. Randomized controlled trials that assessed the efficacy of GCBT for
      PTSD were included in the meta-analysis. A total of 651 participants with PTSD
      were included in the 12 eligible GCBT treatment conditions (5 conditions included
      in-group exposure, 7 conditions did not include in-group exposure). The overall
      pre-post effect size of GCBT for PTSD (ES=1.13 [SE=0.22, 95% CI: 0.69 to 1.56,
      p<.001]). suggests that GCBT is an effective intervention for individuals with
      PTSD. No significant differences in effect sizes were found between GCBT
      treatments that included in-group exposure and those that did not. Although the
      attrition rate was higher in treatments that included exposure in-group, this
      rate is comparable to attrition rates in individual CBT treatments and
      pharmacotherapy for PTSD. The results from this meta-analysis suggest that
      concerns about the potentially negative impact of group exposure may be
      unwarranted, and support the use of exposure-based GCBT as a promising treatment
      option for PTSD.

PMID- 23123570
TI  - Psychotherapy for military-related posttraumatic stress disorder: review of the
      evidence.
AB  - Approximately 20% of the two million troops who have deployed to Iraq and
      Afghanistan may require treatment for posttraumatic stress disorder (PTSD). We
      review treatment outcome studies on individual outpatient therapy for military
      related PTSD, and consider the extent to which veterans initiate and complete
      available PTSD treatments. We conclude with considerations for future research.

PMID- 23123571
TI  - Glucan from hot aqueous extract of an ectomycorrhizal edible mushroom, Russula
      albonigra (Krombh.) Fr.: structural characterization and study of immunoenhancing
      properties.
AB  - A water soluble glucan (PS-I) was isolated from the hot aqueous extract of the
      fruit bodies of an ectomycorrhizal edible mushroom, Russula albonigra (Krombh.)
      Fr. The total hydrolysis, methylation analysis, periodate oxidation, and NMR
      ((1)H, (13)C, DEPT-135, TOCSY, DQF-COSY, NOESY, ROESY, HSQC, and HMBC) studies
      revealed the presence of the following repeating unit in the polysaccharide: This
      glucan showed excellent activation of macrophages as well as splenocytes and
      thymocytes in vitro.

PMID- 23123569
TI  - Sleep disturbance and cognitive deficits in bipolar disorder: toward an
      integrated examination of disorder maintenance and functional impairment.
AB  - Bipolar disorder is frequently associated with a number of poor outcomes
      including, but not limited to, a significant impairment in the ability to return
      to premorbid levels of occupational and psychosocial functioning, often despite
      the remission of mood symptoms. Sleep disturbance is an oft-reported residual
      symptom of manic and depressive episodes that has likewise been associated with
      the onset of manic episodes. Also present during affective episodes as well as
      the inter-episode periods are reports of deficits in cognitive functioning, which
      many reports have shown to play an important role in this persistent disability.
      Despite the presence of deficits in these two domains of functioning during
      affective episodes as well as the inter-episode phase, there has been no
      evaluation of the degree to which these systems may interact to maintain such
      high rates of functional disability. The aim of this review is to examine
      evidence for the study of the relationship between sleep disturbance and
      cognitive impairments in bipolar disorder as well as the ways in which deficits
      in these domains may work together to maintain functional impairment.

PMID- 23123567
TI  - Assessing mental imagery in clinical psychology: a review of imagery measures and
      a guiding framework.
AB  - Mental imagery is an under-explored field in clinical psychology research but
      presents a topic of potential interest and relevance across many clinical
      disorders, including social phobia, schizophrenia, depression, and post-traumatic
      stress disorder. There is currently a lack of a guiding framework from which
      clinicians may select the domains or associated measures most likely to be of
      appropriate use in mental imagery research. We adopt an interdisciplinary
      approach and present a review of studies across experimental psychology and
      clinical psychology in order to highlight the key domains and measures most
      likely to be of relevance. This includes a consideration of methods for
      experimentally assessing the generation, maintenance, inspection and
      transformation of mental images; as well as subjective measures of
      characteristics such as image vividness and clarity. We present a guiding
      framework in which we propose that cognitive, subjective and clinical aspects of
      imagery should be explored in future research. The guiding framework aims to
      assist researchers in the selection of measures for assessing those aspects of
      mental imagery that are of most relevance to clinical psychology. We propose that
      a greater understanding of the role of mental imagery in clinical disorders will
      help drive forward advances in both theory and treatment.

PMID- 23123572
TI  - Behaviour of xyloisosaccharinic acid and xyloisosaccharino-1,4-lactone in aqueous
      solutions at varying pHs.
AB  - Xyloisosaccharinic acid is one of the major degradation products formed during
      the alkali catalysed hydrolysis of hemicelluloses. In acidic solution
      xyloisosaccharinic acid undergoes an acid catalysed lactonisation to generate
      xyloisosaccharino-1,4-lactone. We report here the solution phase properties of
      xyloisosaccharinic including measurement of its aqueous pK(a) (3.00 +/- 0.05)
      using (13)C NMR methods. We also report rate constants for the acid catalysed
      lactonisation, k(lact(D20)), of xyloisosaccharinic acid and the results of our
      investigations of the kinetics of hydrolysis of xyloisosaccharino-1,4-lactone at
      acidic and basic pHs. The second-order rate constants for the hydrolysis
      reactions k(HO-) (25 M(-1)s(-1)) and k(D+) (4.13 E-4M(-1)s(-1)).

PMID- 23123573
TI  - Conversion of fructose, glucose, and cellulose to 5-hydroxymethylfurfural by
      alkaline earth phosphate catalysts in hot compressed water.
AB  - The phosphates of alkaline earth metals (calcium and strontium) synthesized by
      precipitation process in acetone-water media system were used as catalysts for
      converting fructose, glucose, and cellulose to 5-hydroxymethylfurfural (HMF)
      under hot compressed water condition. It was found that the phosphates of calcium
      and strontium effectively catalyzed the HMF formation from fructose and glucose
      dehydration and cellulose hydrolysis/dehydration reaction, as compared with the
      non-catalytic system. The XRD analysis confirmed the CaP(2)O(6) and alpha
      Sr(PO(3))(2) crystalline phases of the catalyst samples, while acid strength of
      both catalysts was in a range of +3.3 <= H(0) <= +4.8. From the study, CaP(2)O(6)
      and alpha-Sr(PO(3))(2) showed similar catalytic performance toward the
      dehydration of sugars, providing the HMF yields of 20-21% and 34-39% from glucose
      and fructose, respectively; whereas the total yield of glucose and HMF from the
      hydrolysis/dehydration of cellulose over alpha-Sr(PO(3))(2) (34%) was higher than
      that over CaP(2)O(6) (17.4%).

PMID- 23123574
TI  - Electron-transfer reduction of 1-deoxy-1-nitroalditols to glycamines with ferrous
      hydroxide.
AB  - Treatment of eight different 1-deoxy-1-nitroalditols with freshly prepared
      ferrous hydroxide at ambient temperature provides the corresponding glycamines
      that were isolated in 81-94% yields as salts with TFA. Under such modified
      reaction conditions, the retro-Henry reaction of the starting compounds is
      significantly suppressed due to the amphoteric character of the reducing agent in
      water. Lower, 58-75% yields were obtained by the classical process with ferrous
      sulfate in aqueous ammonia and employing an improved purification procedure for
      the product glycamines by irreversible capture of sulfate ions with barium
      carbonate.

PMID- 23123575
TI  - First total chemical synthesis of natural acyl derivatives of some
      phenolglycosides of the family Salicaceae.
AB  - The total synthesis of certain natural phenolglycosides of the family Salicaceae,
      namely: salireposide, populosides A, B, and C and not occurring in plants
      desoxysalireposide (2-(beta-D-glucopyranosyloxy)-benzylbenzoate) and per-acetate
      of iso-salireposide (2-(beta-D-glucopyranosyloxy)-5-benzoyloxy benzyl alcohol),
      starting from readily available phenols and glucose was accomplished. A simple
      method for the synthesis of phenolglycosides derivatives of 2-acyloxy salicyl and
      gentisyl alcohol was developed. The key step of these natural products' synthesis
      is a selective removal of acetyl groups in the presence of other acyl groups.

PMID- 23123576
TI  - Comparison of methods to estimate health state utilities for ovarian cancer using
      quality of life data: a Gynecologic Oncology Group study.
AB  - BACKGROUND: Cost-effectiveness/cost-utility analyses are increasingly needed to
      inform decisions about care. Algorithms have been developed using the Functional
      Assessment of Cancer Therapy (FACT) quality of life instrument to estimate
      utility weights for cost analyses. This study was designed to compare these
      algorithms in the setting of ovarian cancer. METHODS: GOG-0152 was a 550-patient
      randomized phase III trial of interval cytoreduction, and GOG-0172 was a 415
      patient randomized phase III trial comparing intravenous versus intraperitoneal
      therapy among women with advanced ovarian cancer. QOL data were collected via the
      FACT at four time points in each study. Two published mapping algorithms (Cheung
      and Dobrez) and a linear transformation method were applied to these data. The
      agreement between measures was assessed by the concordance correlation
      coefficient (r(CCC)), and paired t-tests were used to compare means. RESULTS:
      While agreement between the estimation algorithms was good (ranged from 0.72 to
      0.81), there were statistically significant (p<0.001) and clinically meaningful
      differences between the scores: mean scores were higher with Dobrez than with
      Cheung or the linear transformation method. Scores were also statistically
      significantly different (p<0.001) between studies. CONCLUSIONS: In the absence of
      prospectively collected utility data, the use of mapping algorithms is feasible,
      however, the optimal algorithm is not clear. There were significant differences
      between studies, which highlight the need for validation of these algorithms in
      specific settings. If cost analyses incorporate mapping algorithms to obtain
      utility estimates, investigators should take the variability into account.

PMID- 23123577
TI  - Novel therapies in the management of type I diabetes mellitus.
AB  - Development of insulin pumps and glucose sensors together with sophisticated
      algoritms and connections leading to closed loop systems will probably soon
      improve and facilitate treatment for many patients with Type 1 diabetes (T1D).
      However, the burden for patients will not disappear completely, and such therapy
      will still require both competence and motivation of patients. Therefore the
      final goal should be either to cure the disease via replacement therapy
      (transplantions) or stop the destructive process, preserve residual insulin
      secretion or even improve via beta cell regeneration. This will give a milder
      disease, a more stable metabolism, simpler treatment and perhaps even cure. It is
      neither necessary nor even plausible that Type 1 diabetes has one single cause or
      pathogenesis. Infections may be one causal factor, and vaccinations will then
      turn the increasing incidence downwards. We will also soon know whether it is
      possible to prevent some cases of T1D by avoiding cow's milk in the early
      nutrition. It is possible that probiotics can influence the gut flora so that the
      gut permeability is normlized and maturation of the immune system is improved
      which may also contribute to less incidence of Type 1 diabetes. However, for
      those who already have got the disease we need interventions to preserve
      exisiting beta cell function and facilitate regeneration of beta-cells. Broader
      immunosuppressive therapies have been disappointing. Phase III studies using
      monocloncal antiCD3 antibodies have recently failed, but one dose regimen showed
      promising effect in patients aged 8-20 years. Therefore furthers studies are
      needed. Autoantigen treatment is a promising concept, and has the great advantage
      of being easy, practical with no adverse events. Diapep277 has shown some
      positive results in adults with good C-peptide, and glutamic acid decarboxylase
      (GAD)-alum has given quite impressive results in children aged 10-20 years, even
      though the results from studies differ. It is time to start combination therapies
      where auto-antigen/s, alone or in combination, are used together with other
      agents such as Vitamin D and anti-inflammatory drugs. We need to learn how to
      treat subgroups of patients. Gradually a more individualized treatment may become
      successful.

PMID- 23123578
TI  - Advances in trans-sphenoidal pituitary surgery.
AB  - Pituitary surgery is a continuous evolving speciality of the neurosurgeons'
      armamentarium, requiring precise anatomical knowledge, technical skills and
      integrated appreciation of the pituitary pathophysiology. Actually, it could be
      considered the result of a close cooperation between different specialists, i.e.
      the ophthalmologist, the neuroradiologist, the endocrinologist, the neurosurgeon,
      the pathologist, etc. In this teamwork environment each member plays his own
      role, offering his contribute to the final result; every effort is performed to
      provide patients with the best possible procedure, individually measured. The
      endoscopic pituitary surgery performed by means of a transsphenoidal approach
      perfectly fits this scenario, being though advocated as the result of an
      evolutionary process rather than a revolutionary one. The "pure" endoscopic
      transsphenoidal surgery - consisting of a whole procedure performed with the
      endoscope alone and without the use of any transsphenoidal retractor - offers
      some advantages due to the endoscope itself: a superior close-up view of the
      relevant anatomy, very important at the tumor/gland interface and an enlarged
      working angle are provided with an increased panoramic vision inside the surgical
      area. Results in terms of mass removal, relief of clinical symptoms, cure of the
      underlying disease and complication rate are similar to those reported in the
      major microsurgical series but patient compliance is by far better.

PMID- 23123579
TI  - Relationship between increased endogenous parathormone levels and bone density in
      postmenopausal women treated with bisphosphonates.
AB  - AIM: Bisphosphonates increase bone mineral density (BMD) and also increase
      parathyroid hormone (PTH): the rule of increased PTH on BMD is not well known.
      The aim of our study was to assess the relationship between endogenous PTH levels
      and BMD after 18 months of antiresorptive therapy in a group of post-menopausal
      women with normal baseline PTH levels. METHODS: A retrospective study was
      conducted on 62 women with normal baseline PTH levels (mean age 62.7 +/- 8.6
      years) who underwent dual-energy X-ray absorptiometry, thoracic-lumbar
      radiography, and blood and urine sampling at the baseline and after 18 months.
      All patients were treated with bisphosphonates and received calcium and vitamin
      D3 supplementation. RESULTS: In the whole group, after 18 months, mean BMD
      improved both at lumbar spine (0.53 +/- 0.09 vs. 0.49 +/- 0.09 g/cm2; P<0.05) and
      at femur (0.66 +/- 0.08 vs. 0.65 +/- 0.09 g/cm2; P<0.05); PTH levels (56.80 +/-
      19.07 vs. 48.74 +/- 14.99 pg/mL; P<0.001) and serum 25-hydroxyvitamin D (60.73 +/
      29.87 vs. 49.81 +/- 26.56 ng/mL; P<0.05) increased. Dividing the patients
      according PTH variation (>0 or <= 0), the group with DeltaPTH>0 had higher
      percentage increase of BMD at spine (8.0 +/- 9% vs. 4 +/- 7.5%; P<0.001) and at
      total hip (3 +/- 9% vs. 0.49 +/- 8.9%; P<0.001) while the bone alkaline
      phosphatase significantly decreased (-11.80 +/- 2.19 vs. -4.05 +/- 3.08 ug/L;
      P<0.001) than the other group. CONCLUSION: Increased endogenous PTH levels seems
      to be associated with a higher BMD increase in patients treated with
      bisphosphonates for postmenopausal osteoporosis. The increase of PTH must be
      clarified by further investigations.

PMID- 23123580
TI  - The borderline personality organization in a dimensional perspective: the TCI and
      SWAP-200 in comparison.
AB  - AIM: The categorical assessment of personality disorders, in particular of the
      borderline personality disorder is being debated by most authors. This study
      focuses on the structural organization of personality, namely on Kernberg's
      borderline personality organization (BPO). It aims to explore the dimensional
      personality assessment and to test the convergence on this construct of two
      dimensional instruments: the Temperament and Character Inventory (TCI) and the
      Shedler-Westen Assessment Procedure (SWAP-200). METHODS: BPO was assessed with
      the Temperament and Character Inventory (TCI) and the Shedler-Westen Assessment
      Procedure (SWAP-200). Thirty-four BPO subjects were recruited in the study. TCI
      profiles of BPO subjects were compared with 34 non-BPO matched controls. TCI and
      SWAP-200 profiles were correlated with each other and with clinical data.
      RESULTS: BPO subjects showed higher harm avoidance and lower self-directedness
      (TCI). The SWAP-200 evidenced a schizotypal configuration (categorical
      classification) and histrionic and schizoid traits (Q-sort classification).
      CONCLUSION: The instruments displayed limited correlation. Instead they both
      extensively correlated with clinical history of BPO subjects. Implications for
      BPO assessment and its relationship with mental disorders are discussed. The
      knowledge of the BPO dimensional characteristics will improve clinical management
      and therapeutic strategies for BPO patients. Moreover the comparison of two
      dimensional instruments on the construct of BPO may shed a light on their
      strengths and weaknesses.

PMID- 23123581
TI  - General practitioners and management of patients with respiratory diseases in a
      real life survey.
AB  - AIM: The prevalence of respiratory diseases has been assessed in community based
      epidemiological studies. General practice is the ideal position to intercept
      chronic respiratory illness and manage the first level of follow up as well. Aim
      of this study was to obtain General Practitioners (GPs) data about management and
      clinical setting of patients with respiratory diseases. METHODS: This is a
      prospective observational study; 272 Italian GPs were involved and equally
      distributed on the Italian territory. The interviews were performed by means of a
      questionnaire consisting in which consisted of 25 questions regarding individual
      demographics, catchment area, professional behavior, health attitudes. RESULTS:
      Each GP reported that about 13% of the pooled patients had a respiratory disease.
      Concerning as for chronic respiratory illnesses, spirometry was frequently
      prescribed and in these patients 63% of the interviewed GPs thought that the lung
      functional test was fundamental. GPs also reported the importance of improving
      health education, well aware of its importance in the prevention of respiratory
      diseases; and furthermore in improving the current health system organization. As
      for with regard to cigarette smoke, interviewed GPs reported that the 26% of
      their assisted subjects were smokers and the commitment to discouraging the
      smoking habit was very high. CONCLUSION: This is a large National survey that
      involved GPs and real life data about management of patients with respiratory
      diseases. The role of GPs in the management of chronic respiratory patients
      represents an important tool valuable in increasing primary care identification,
      education and treatment of respiratory diseases.

PMID- 23123582
TI  - PEDF inhibits growth and invasiveness of endometrial cancer cells in vitro.
AB  - AIM: Pigment epithelium-derived factor (PEDF) is pluripotent in both
      antiangiogenesis and direct tumor inhibition. We thus investigated role of PEDF
      in endometrial cancer cells in vitro. METHODS: Exogenous PEDF was delivered into
      Ishikawa and KLE cells by adenovirus system. Realtime RT-PCR was used to detect
      expressional change of several angiogenesis-related factors. Proliferation and
      viability tests were performed to establish suitable transduction titre. Cell
      cycle and apoptosis assays were conducted to evaluate inhibitive effects of PEDF
      on tumor cell growth. Transwell tests were carried out to investigate the
      retardation of tumor cell invasiveness by PEDF. RESULTS: PEDF induced decrease in
      viability, proliferation and invasiveness of both endometrial tumor cell lines.
      Incremented cell apoptosis and aggregated population in G1 phase of cell cycle
      was noted in PEDF groups. PEDF also induced down-regulation of vascular
      endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) and up
      regulation of thrombospondin-1 (TSP-1) in both cell lines. CONCLUSION: Adenovirus
      mediated PEDF is potent in retarding the growth and invasiveness of endometrial
      cancer cells. PEDF can become promising as novel therapeutic strategy in
      endometrial carcinoma.

PMID- 23123583
TI  - The anti-IgE antibody omalizumab as a probe to investigate the role of IgE in
      pathology.
AB  - The immunoglobulin E (IgE) are a key factor in the pathophysiology of allergic
      diseases and the important therapeutic role of an anti-IgE antibody was long
      envisioned. It took time and efforts to solve the safety problems related to the
      anaphylactogen capacity of anti-IgE, finally crowned by the introduction of the
      humanized, monoclonal anti-IgE antibody omalizumab. Currently, omalizumab is
      indicated, based on clear evidence of efficacy, only in severe allergic asthma
      not controlled by conventional treatment. However, a continuously increasing
      amount of literature shows that omalizumab is efficacious in a number of
      disorders concerning the upper and lower airway and the skin, and, most
      importantly, in anaphylaxis. The latter application was demonstrated successful
      in placebo-controlled trials and warrants for a new, life-saving, indication for
      omalizumab. Also, the systemic reactions precluding the performance of allergen
      immunotherapy, especially concerning Hymenoptera venom, were prevented by
      omalizumab treatment. The most surprising success of omalizumab regards clinical
      conditions thus far considered unrelated to IgE antibodies. This is true for
      intrinsic asthma and for idiopathic urticaria (demonstrated by a placebo
      controlled trial), and angioedema, suggesting in these condition a
      pathophysiologic role of IgE. These observations support a off-label use of
      omalizumab in patients suffering from IgE-related pathologies other than asthma
      who are at risk of fatal events or are uncontrolled by the optimal standard
      treatment.

PMID- 23123584
TI  - Extrahepatic spread of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a major health problem. The treatment of HCC
      depends on the tumour stage and on the severity of underlying cirrhosis, however,
      a majority of HCC patients have advanced disease at presentation. In recent years
      extra-hepatic spread (ES) of HCC seems to have been observed more frequently than
      in the past even if few data exist in literature on prevalence, clinical
      presentation and prognosis of patients with HCC ES. Aim of this brief review is
      underline the main concerns, pitfalls and warnings in practicing with these
      patients. ES of HCC are not rare, and the probability of finding ES is higher in
      patients with advanced intra-hepatic HCC. The more frequent ES sites are lung
      lymph nodes and bones, but also the head and neck district can be affected. The
      prognosis of HCC patients with ES is poor and sorafenib seems to be the only
      therapeutic option.

PMID- 23123585
TI  - Quality of life, mood disturbances and psychological parameters in adult patients
      with GH deficiency.
AB  - An increased prevalence of depression, emotional lability, decreased energy
      levels, and poor quality of life have been reported in adults with GH deficiency
      (GHD). The impairment of psychological parameters depends on the aetiology of GHD
      and the presence of other pituitary hormone deficiencies because of hormonal
      effects on neural cell metabolism. Cognitive dysfunctions appear to be
      specifically related to GHD itself, whereas the lower emotional well-being and
      reduced motor performance are attributed to other pituitary hormone deficiencies.
      Traumatic Brain Injury causes very often hypopituitarism and GHD as well as other
      many psychological symptoms: cognitive impairment, sleeping disorders, and
      depression. Many neurobehavioral symptoms of postconcussion syndrome (PCS) are
      the same suffered by adult GHD and hypopituitaric patients but there are no data
      about the occurrence of hypopituitarism in PCS. In some studies treatment with
      rhGH is reported to have a beneficial effect and GHD could contribute itself to
      the global impairment of psychological dysfunctions. The link between
      psychosocial impairments and GHD is not fully understood. The effects of long
      term rhGH therapy on cognitive functions are largely unknown. Thus, long-term
      placebo-controlled double-blind studies are required to investigate whether
      psychological dysfunctions are reversible on GH substitution.

PMID- 23123586
TI  - Transgenic mice with high endogenous omega-3 fatty acids are protected from
      spinal cord injury.
AB  - Omega-3 polyunsaturated fatty acids have been shown to have therapeutic potential
      in a variety of neurological disorders, including acute traumatic injury of the
      spinal cord. We addressed the question whether the neuroprotective effect of
      these compounds after spinal cord injury could also be seen when their level is
      raised in tissues prophylactically, prior to injury. In this study we used
      transgenic fat-1 mice to examine whether enriching spinal cord tissue in
      endogenous omega-3 polyunsaturated fatty acids has an effect on the outcome after
      compression spinal cord injury. The results demonstrate that after thoracic
      compression spinal cord injury, fat-1 mice display better locomotor recovery
      compared with the wild-type mice on a high omega-6 diet (high omega-6
      polyunsaturated fatty acids in tissues), and wild-type mice on a normal diet
      (controls). This is associated with a significant increase in neuronal and
      oligodendrocyte survival and a decrease in non-phosphorylated neurofilament loss.
      The protection from spinal cord injury in fat-1 mice was also correlated with a
      reduction in microglia/macrophage activation and in pro-inflammatory mediators.
      In vitro experiments in dorsal root ganglia primary sensory neurons further
      demonstrated that a fat-1 tissue background confers robust neuroprotection
      against a combined mechanical stretch and hypoxic injury. In conclusion, our
      studies support the hypothesis that a raised omega-3 polyunsaturated fatty acid
      level and an altered tissue omega-6/omega-3 ratio prior to injury leads to a much
      improved outcome after spinal cord injury.

PMID- 23123587
TI  - Loss of Tsc2 in Purkinje cells is associated with autistic-like behavior in a
      mouse model of tuberous sclerosis complex.
AB  - Tuberous sclerosis complex (TSC) is a dominant tumor suppressor disorder caused
      by mutations in either TSC1 or TSC2. TSC causes substantial neuropathology, often
      leading to autism spectrum disorders (ASDs) in up to 60% of patients. The
      anatomic and neurophysiologic links between these two disorders are not well
      understood. We have generated and characterized a novel TSC mouse model with
      Purkinje cell specific Tsc2 loss. These Tsc2f/-;Cre mice exhibit progressive
      Purkinje cell degeneration. Since loss of Purkinje cells is a well reported
      postmortem finding in patients with ASD, we conducted a series of behavior tests
      to asses if Tsc2f/-;Cre mice displayed autistic-like deficits. Tsc2f/-;Cre mice
      demonstrated increased repetitive behavior as assessed with marble burying
      activity. Using the three chambered apparatus to asses social behavior, we found
      that Tsc2f/-;Cre mice showed behavioral deficits, exhibiting no preference
      between a stranger mouse and an inanimate object, or between a novel and a
      familiar mouse. We also detected social deficits in Tsc2f/f;Cre mice, suggesting
      that Purkinje cell pathology is sufficient to induce ASD-like behavior.
      Importantly, social behavior deficits were prevented with rapamycin treatment.
      Altogether, these results demonstrate that loss of Tsc2 in Purkinje cells in a
      Tsc2-haploinsufficient background leads to autistic-like behavioral deficits.
      These studies provide compelling evidence that Purkinje cell loss and/or
      dysfunction may be an important link between TSC and ASD as well as a general
      anatomic phenomenon that contributes to the ASD phenotype.

PMID- 23123588
TI  - Modifiable risk factors for schizophrenia and autism--shared risk factors
      impacting on brain development.
AB  - Schizophrenia and autism are two poorly understood clinical syndromes that differ
      in age of onset and clinical profile. However, recent genetic and epidemiological
      research suggests that these two neurodevelopmental disorders share certain risk
      factors. The aims of this review are to describe modifiable risk factors that
      have been identified in both disorders, and, where available, collate salient
      systematic reviews and meta-analyses that have examined shared risk factors.
      Based on searches of Medline, Embase and PsycINFO, inspection of review articles
      and expert opinion, we first compiled a set of candidate modifiable risk factors
      associated with autism. Where available, we next collated systematic-reviews
      (with or without meta-analyses) related to modifiable risk factors associated
      with both autism and schizophrenia. We identified three modifiable risk factors
      that have been examined in systematic reviews for both autism and schizophrenia.
      Advanced paternal age was reported as a risk factor for schizophrenia in a single
      meta-analysis and as a risk factor in two meta-analyses for autism. With respect
      to pregnancy and birth complications, for autism one meta-analysis identified
      maternal diabetes and bleeding during pregnancy as risks factors for autism
      whilst a meta-analysis of eight studies identified obstetric complications as a
      risk factor for schizophrenia. Migrant status was identified as a risk factor for
      both autism and schizophrenia. Two separate meta-analyses were identified for
      each disorder. Despite distinct clinical phenotypes, the evidence suggests that
      at least some non-genetic risk factors are shared between these two syndromes. In
      particular, exposure to drugs, nutritional excesses or deficiencies and
      infectious agents lend themselves to public health interventions. Studies are now
      needed to quantify any increase in risk of either autism or schizophrenia that is
      associated with these modifiable environmental factors.

PMID- 23123589
TI  - The relationship between egalitarianism, dominance, and violence in intimate
      relationships.
AB  - The aim of this study was to understand the relationship between egalitarianism,
      dominance, and intimate partner violence within the context of couples' dynamics.
      In particular, it was hypothesized that dominance and sexist attitudes would have
      both self and partner effects on relationship aggression. To test this
      hypothesis, gender role egalitarianism, dominance/control, sexism, power
      dynamics, and aggression were assessed using several measures. Questionnaires for
      these measures were completed by 87 heterosexual dyads. The relationship between
      female and male scores on the dominance, egalitarianism, sexism, and intimate
      partner violence scales were examined using Actor-Partner Interdependence Model
      (APIM). Findings indicated that the APIM model provided a satisfactory fit to the
      data(). For both sexes, dominance had more explanatory power than sexism and
      egalitarianism when all else was controlled in the model. Furthermore, contrary
      to our expectation, male egalitarian attitude had no significant actor or partner
      effect on relationship aggression, while female egalitarian attitude had
      significant actor and partner effects on relationship aggression. Dyadic analysis
      indicated that cultural pointers of patriarchy, such as egalitarianism among
      young college students, were not associated with male-to-female violence. The
      sample size might also have an effect on this result in that a larger sample with
      older participants might yield different results.

PMID- 23123590
TI  - Response to letter: "Role of intra-aortic balloon pumping on cerebral perfusion
      after cardiac arrest".

PMID- 23123591
TI  - Role of intra-aortic balloon pumping on cerebral perfusion after cardiac arrest.

PMID- 23123592
TI  - Spectroscopic studies on the binding of holmium-1,10-phenanthroline complex with
      DNA.
AB  - Fluorescence and absorption spectroscopy, circular dichroism (CD) as well as
      viscosity experiment have been used to characterize the DNA binding of
      [Ho(Phen)(2)Cl(3)].H(2)O, where phen stand for 1,10-phanathroline. This complex
      exhibits the marked decrease in the emission intensity and some hypochromism in
      UV-Vis spectrum in the presence of DNA. For characterization of the binding mode
      between the Ho(III) complex and DNA various procedures such as: absorption and
      emission titration and EB quenching experiments, viscosity measurements, CD
      study, iodide quenching assay, salt effect and thermodynamical investigation are
      used. The intrinsic binding constant of [Ho(Phen)(2)Cl(3)].H(2)O with DNA is
      calculated by UV-Vis and florescence spectroscopy. The value of binding constants
      in 296, 299 and 303 are 1.99 +/- 0.07 * 10(4), 1.07 +/- 0.09 * 10(4) and 0.84 +/-
      0.06 * 10(4), respectively. The thermodynamic studies show that the reaction is
      entropically driven. The above-mentioned physical measurements indicate that the
      Ho(III) complex binds to fish salmon DNA, presumably via groove binding mode.

PMID- 23123593
TI  - Photodegradation of thermally modified wood.
AB  - Natural wood, being biological material, undergoes rapid degradation by
      ultraviolet (UV) radiations and other environmental factors under outdoor
      exposure. In order to protect wood from such degradation, the chemical structure
      of wood is altered by chemical modification or heat treatment. In the present
      study, heat treated specimens of rubberwood (Hevea brasiliensis) were exposed to
      xenon light source in a weather-o-meter for different periods up to 300 h.
      Photostability of modified and unmodified wood was evaluated in terms of colour
      and chemical changes. Light coloured untreated wood became dark upon UV
      irradiation whereas, dark colour of heat treated wood lightened on UV exposure.
      CIE lightness parameter (L(*)) decreased for untreated wood whereas its value
      increased for heat treated wood upon irradiation. Other colour coordinates a(*)
      and b(*) increased with exposure duration for both untreated and heat treated
      wood. The overall colour change (DeltaE(*)) increased for both untreated and heat
      treated wood. The Fourier Transform Infrared (FTIR) spectroscopic studies
      revealed severe lignin degradation of heat treated wood due to UV light exposure.
      Colour changes and FTIR measurements indicate that thermal modification of wood
      was ineffective in restricting light induced colour changes and photodegradation
      of wood polymers.

PMID- 23123594
TI  - Efficacy of antioxidants in human hair.
AB  - Hair is exposed every day to a range of harmful effects such as sunlight,
      pollution, cosmetic treatments, grooming practices and cleansing. The UV
      components of sunlight damage human hair, causing fibre degradation. UV-B attacks
      the melanin pigments and the protein fractions (keratin) of hair and UV-A
      produces free radical/reactive oxygen species (ROS) through the interaction of
      endogenous photosensitizers. Hair was dyed and the efficacy of two antioxidant
      formulations was demonstrated after UV exposure by evaluating, surface
      morphology, protein and amino acid degradation, lipidic peroxidation, colour and
      shine changes and strength/relaxation properties. UV treatment resulted in an
      increase in protein and lipid degradation, changes in colour and shine and in
      adverse consequences for the mechanical properties. Natural antioxidants obtained
      from artichoke and rice applied to pretreated hair improved mechanical properties
      and preserved colour and shine of fibres, coating them and protecting them
      against UV. Furthermore, the lipidic peroxidation of the protein degradation
      caused by UV was reduced for some treated fibres, suggesting an improvement in
      fibre integrity. This was more marked in the case of the fibres treated using the
      artichoke extract, whereas the rice extract was better preserving shine and
      colour of hair fibres.

PMID- 23123595
TI  - In vitro phototoxicity of ultradeformable liposomes containing chloroaluminum
      phthalocyanine against New World Leishmania species.
AB  - The use of photodynamic therapy (PDT) against cutaneous leishmaniasis (CL) based
      on chloroaluminum phthalocyanine (ClAlPc) is a promissory alternative therapy.
      The main purpose of this article was to assess the internalization and in vitro
      phototoxic activities of ClAlPc encapsulated in ultradeformable liposomes (UDL
      ClAlPc) in Leishmania parasites and mammalian cells. Cell internalization was
      determined by fluorescence microscopy, cell and parasite damage by standard MTT
      or direct microscopic analysis and a phototoxic index (PI) was calculated as the
      compound activity (IC(50)) at 0 J/cm(2)/IC(50) at 17 J/cm(2). Liposomal and free
      ClAlPc were internalized by infected and non-infected THP-1 cells and co
      localized in the mitochondria. Treatment of UDL-ClAlPc was almost 10 times more
      photoactive than free ClAlPc on THP-1 cells and promastigotes and intracellular
      amastigotes of Leishmania chagasi and Leishmania panamensis. Liposomal compounds
      were active on non-irradiated and irradiated cells however PI higher than 50 were
      calculated. PI for amphotericin B referential drug were lower than 1.2. Empty
      liposomes tested at the same lipid concentration of active ClPcAl-liposomes were
      non-toxic. Upon photodynamic treatment a nonselective-parasite activity against
      intracellular amastigotes were observed and loss of membrane integrity resulting
      in a release of parasites was detected. Further studies oriented to evaluate both
      the state of infection after PDT and the effectiveness of UDL as delivery
      vehicles of ClAlPc in CL experimental models are required.

PMID- 23123596
TI  - Bioluminescence as a tool for studying detoxification processes in metal salt
      solutions involving humic substances.
AB  - The paper considers effects of humic substances (HS), as natural attenuators of
      toxicity, on solutions of model inorganic pollutants, metal salts - Pb(NO(3))(2),
      SoSl(2), CuSO(4), Eu(NO(3))(3), SrSl(3), and K(3)[Fe(SN)(6)]. Luminous bacteria
      Photobacterium phosphoreum and bioluminescent system of coupled enzymatic
      reactions were used as bioassays to monitor toxicity of salt solutions. The
      ability of HS to decrease or increase toxicity was demonstrated. Detoxifying
      concentrations of HS were determined; detoxification coefficients were calculated
      at different times of exposure of salt solutions to HS. To study the combined
      effects of HS and salts on bioluminescent assay systems, the rates of biochemical
      reactions and bacterial ultrastructure were analyzed. The detoxifying effects
      were explained by: (1) decrease of free metal content in water solutions under
      metal-HS binding; (2) increase of biochemical reaction rates in a bioluminescent
      assay system under HS effect; (3) enhancement of mucous layers on cell surface as
      a response to unfavorable impact of toxicants. Detoxifying mechanisms (2) and (3)
      reveal the active role of bioassay systems in detoxification processes.

PMID- 23123597
TI  - Purple rice extract and its constituents suppress endoplasmic reticulum stress
      induced retinal damage in vitro and in vivo.
AB  - AIMS: Endoplasmic reticulum (ER) stress has been implicated as a cause of various
      neurodegenerative diseases. We evaluated the protective effects of purple rice
      (Oryza sativa L.) bran extract (PRE) and its constituents, namely cyanidin,
      peonidin, and a newly isolated compound 2-hydroxy-5-[(3S)-3-hydroxybutyl]phenyl
      beta-D-glucoside (HHPG), against tunicamycin-induced retinal damage. MAIN
      METHODS: In an in vitro experiment, protective effects of PRE, cyanidin and HHPG
      on cultured retinal ganglion cells (RGC-5), which were damaged by treatment with
      H(2)O(2) or tunicamycin for 24 h, were evaluated. We also investigated the
      underlying mechanism by examining expressions of ER stress-related proteins, such
      as immunoglobulin heavy-chain binding protein (BiP) and C/EBP homologous protein
      (CHOP), and activation of caspase-3 induced by tunicamycin. In an in vivo
      experiment, mice retinal damage was induced by intravitreous injection of
      tunicamycin as revealed by histological analysis using hematoxylin-eosin
      staining. KEY FINDINGS: The viability of H(2)O(2) or tunicamycin-treated RGC-5,
      assessed using the tetrazolium salt (WST-8) assay, was improved by treatment with
      PRE, cyanidin, and HHPG, respectively. PRE did not affect tunicamycin-induced
      expressions of BiP or CHOP. However, PRE, cyanidin, and HHPG suppressed
      tunicamycin-induced caspase-3 activation. Histological analysis using hematoxylin
      eosin staining showed that intravitreous injection of PRE significantly
      suppressed the tunicamycin-induced degeneration of retinal ganglion cells in
      mice. SIGNIFICANCE: These findings indicate that PRE, cyanidin, and HHPG suppress
      tunicamycin-induced retinal ganglion cell death at least partly by inhibiting
      activation of caspase-3, suggesting that PRE and its main constituents prevent
      retinal disease caused by ER stress.

PMID- 23123600
TI  - A web of streamers: biofilm formation in a porous microfluidic device.
AB  - Using a microfabricated porous media mimic platform, we investigated how fluid
      flow influences the formation of filamentous structures, known as streamers,
      between porous media structures. We demonstrate how hydrodynamics govern the
      formation, morphology and the distribution of these biofilm streamers in the
      device. Our work establishes that, under favorable hydrodynamic conditions,
      streamers can often act as precursors to mature microbial structures found in
      complex geometries, such as those involved in porous media.

PMID- 23123598
TI  - Fibroblasts as architects of cancer pathogenesis.
AB  - Studies of epithelial cancers (i.e., carcinomas) traditionally focused on
      transformation of the epithelium (i.e., the cancer cells) and how aberrant
      signaling within the cancer cells modulates the surrounding tissue of origin. In
      more recent decades, the normal cells, blood vessels, molecules, and
      extracellular components that surround the tumor cells, collectively known as the
      "tumor microenvironment" or "stroma", have received increasing attention and are
      now thought to be key regulators of tumor initiation and progression. Of
      particular relevance to the work reviewed herein are the fibroblasts, which make
      up the major cell type within the microenvironment of most carcinomas. Due to
      their inherent heterogeneity, plasticity, and function, it is perhaps not
      surprising that fibroblasts are ideal modulators of normal and cancerous
      epithelium; however, these aspects also present challenges if we are to interrupt
      their tumor-supportive functions. Here, we review the current body of knowledge
      and the many questions that still remain about the special entity known as the
      cancer-associated fibroblast. This article is part of a Special Issue entitled:
      Fibrosis: Translation of basic research to human disease.

PMID- 23123599
TI  - SR-A deficiency reduces myocardial ischemia/reperfusion injury; involvement of
      increased microRNA-125b expression in macrophages.
AB  - The macrophage scavenger receptor class A (SR-A) participates in the innate
      immune and inflammatory responses. This study examined the role of macrophage SR
      A in myocardial ischemia/reperfusion (I/R) injury and hypoxia/reoxygenation (H/R)
      induced cell damage. SR-A(-/-) and WT mice were subjected to ischemia (45min)
      followed by reperfusion for up to 7days. SR-A(-/-) mice showed smaller myocardial
      infarct size and better cardiac function than did WT I/R mice. SR-A deficiency
      attenuated I/R-induced myocardial apoptosis by preventing p53-mediated Bak-1
      apoptotic signaling. The levels of microRNA-125b in SR-A(-/-) heart were
      significantly greater than in WT myocardium. SR-A is predominantly expressed on
      macrophages. To investigate the role of SR-A macrophages in H/R-induced injury,
      we isolated peritoneal macrophages from SR-A deficient (SR-A(-/-)) and wild type
      (WT) mice. Macrophages were subjected to hypoxia followed by reoxygenation. H/R
      markedly increased NF-kappaB binding activity as well as KC and MCP-1 production
      in WT macrophages but not in SR-A(-/-) macrophages. H/R induced caspase-3/7 and 
      8 activities and cell death in WT macrophages, but not in SR-A(-/-) macrophages.
      The levels of miR-125b in SR-A(-/-) macrophages were significantly higher than in
      WT macrophages. Transfection of WT macrophages with miR-125b mimics attenuated
      H/R-induced caspase-3/7 and -8 activities and H/R-decreased viability, and
      prevented H/R-increased p-53, Bak-1 and Bax expression. The data suggest that SR
      A deficiency attenuates myocardial I/R injury by targeting p53-mediated apoptotic
      signaling. SR-A(-/-) macrophages contain high levels of miR-125b which may play a
      role in the protective effect of SR-A deficiency on myocardial I/R injury and H/R
      induced cell damage.

PMID- 23123601
TI  - Measurements of system sharpness for two digital breast tomosynthesis systems.
AB  - The aim of this work was to propose system sharpness parameters for digital
      breast tomosynthesis (DBT) systems that include the influence of focus size and
      focus motion for use in quality assurance protocols. X-ray focus size was
      measured using a multiple pinhole test object, while detector presampling
      modulation transfer function (MTF) was measured from projection images of a 10 cm
      * 10 cm, 1 mm thick steel edge, for the Siemens Inspiration and Hologic Selenia
      Dimensions DBT systems. The height of the edge above the table was then varied
      from 1 to 78 mm. The MTF expected from theory for the projection images was
      calculated from the measured detector MTF, focus size MTF and focus motion MTF
      and was compared against measured curves. Two methods were used to measure the in
      plane MTF in the DBT volume: a tungsten wire of diameter 25 um and an Al edge 0.2
      mm thick, both imaged with a 15 mm thick poly(methyl methacrylate) (PMMA) plate.
      The in-depth point spread function (PSF) was measured using an angled tungsten
      wire. The full 3D MTF was estimated with a 0.5 mm diameter aluminium bead held in
      a 45 mm thick PMMA phantom, with the bead 15 and 65 mm above the table.
      Inspiration DBT projection images are saved at native detector resolution (85
      um), while the Dimensions re-bins projections to 140 um pixels (2 * 2 binning);
      both systems used 2 * 2 binning of projection data before reconstruction. The 50%
      point for the MTF (MTF(0.50)) measured in the DBT projection images for the tube
      travel direction fell as a function of height above the table from 3.60 to 0.90
      mm(-1) for the Inspiration system and from 2.50 to 1.20 mm(-1) for the Dimensions
      unit. The maximum deviation of measured MTF(0.50) from the calculated value was
      13%. MTF(0.50) measured in-plane (tube-travel direction) fell as a function of
      height above the table from 1.66 to 0.97 mm(-1) for the Inspiration system and
      from 2.21 to 1.31 mm(-1) for the Dimensions system. The full-width half-maximum
      for the in-depth PSF was 3.0 and 5.9 mm for the Inspiration and Dimensions
      systems, respectively. There was no difference in the 3D MTF curves, sectioned in
      the tube-travel direction, for bead heights of 15 and 65 mm above the table. A 25
      um tungsten wire held within a 15 mm thick PMMA plate was found to be a suitable
      test object for measurement of in-plane MTF. Evaluation of MTF as a function of
      height above the table, both in the projection images and in the reconstructed
      planes, provides important information on the impact of focus size and focus
      motion on the DBT system's imaging performance.

PMID- 23123602
TI  - Electrophysiological importance of embryonic stem cell-derived cardiac
      progenitors.

PMID- 23123603
TI  - Impact of ischemia-guided initial diagnosis in patients with stable angina.

PMID- 23123604
TI  - The "double wrist flexor" tendon transfer for radial nerve palsy.
AB  - In isolated high radial nerve palsy, it is traditionally taught that one should
      not use both wrist flexors for tendon transfers. Over the last 17 years, the
      author has encountered 4 unusual cases of high radial nerve palsy with concurrent
      direct injury to the pronator teres, flexor digitorum superficialis, and the
      palmaris longus in the proximal forearm. In these cases, the author used both
      wrist flexors, namely, the flexor carpi radialis to restore wrist extension and
      the flexor carpi ulnaris to restore finger/thumb extension as well as thumb
      radial abduction. Despite the major loss of wrist flexion, all patients had a
      good overall function as per the modified Bincaz scale. It was concluded that
      this "double wrist flexor" transfer remains to be an acceptable option for high
      radial nerve palsy when the pronator teres, flexor digitorum superficialis, and
      the palmaris longus tendons are not available.

PMID- 23123605
TI  - The impact of breast reduction surgery on the vertebral column.
AB  - BACKGROUND: Although many studies have shown that breast reduction surgery is
      effective in reducing neck, back, and lumbar pain, most of these studies are
      subjective evaluations that usually provide data through pain scales. This study
      was undertaken to objectively evaluate the radiologic effects of breast reduction
      on the vertebral column. METHODS: Thirty patients who underwent breast reduction
      surgery were included in the study. A lateral thoracolumbar radiograph was taken
      before and 3 months after surgery for each patient. The thoracic kyphosis, lumbar
      lordosis, and sacral inclination angles were measured for each radiograph. The
      impact of breast reduction surgery on posture was evaluated according to the
      comparison of these angles before and after surgery. The effect of age, body mass
      index, and the total amount of removed tissue was also taken into account, and
      the relationship between these parameters and their effects on the change in
      preoperative and postoperative angle measurements were evaluated. RESULTS: There
      was a significant decrease in all 3 angles after breast reduction surgery. A
      significant correlation was determined between body mass index and the total
      amount of removed tissue on the change in angle measurements, whereas a definite
      relationship was not observed between the angles and the patient's age.
      CONCLUSIONS: This study has shown the objective impact that breast reduction
      surgery has on the vertebral column. Although the symptomatic relief of breast
      reduction surgery on the musculoskeletal system is widely accepted, the objective
      assessment of this relief will be beneficial in persuading health insurance
      companies and those who think of this surgery as a purely aesthetic procedure.

PMID- 23123606
TI  - Candida albicans necrotizing soft tissue infection: a case report and literature
      review of fungal necrotizing soft tissue infections.
AB  - BACKGROUND: Necrotizing fasciitis (NF) most often is caused by bacterial
      infection while a fungal source has been reported in immunosuppressed patients.
      Early wide surgical resection remains the mainstay of treatment. Split thickness
      skin grafts are both versatile and easy to harvest, thus making them a long
      established option for soft tissue reconstruction. CASE REPORT: A 55-year-old man
      was admitted for gunshot wounds. Purulence was noted at the central catheter
      site. Cultures grew Candida albicans. Antifungal therapy was initiated and
      debridement for NF of the neck and upper chest was performed. The patient
      underwent reconstruction using a split thickness skin graft obtained from the
      anterolateral thigh. CONCLUSIONS: Necrotizing fasciitis secondary to Candida
      species infection is exceedingly rare. We report an unusual case of candidal NF
      in a patient with no past medical history of immunocompromise. Patients with this
      type of infection can be successfully treated with aggressive surgical
      debridement and intravenous anidulafungin.

PMID- 23123607
TI  - Aesthetic subunit of the breast: an analysis of women's preference and clinical
      implications.

PMID- 23123608
TI  - The use of free microvascular techniques to improve the results of Van Nes
      rotationplasty.
AB  - Van Nes rotationplasty is a limb-salvage used for reconstruction after resection
      of a distal femoral or proximal tibial osteosarcoma in the pediatric patient.
      After resection, the distal leg is reapproximated to the level of tumor
      resection. The goal is to optimize extremity functionality such that the ankle
      functions as a knee joint. Traditionally, the vessels and nerves around the tumor
      are preserved within the distal leg. In the first case of our series, this method
      resulted in thrombosis, flap loss, and ultimately amputation secondary to venous
      torsion and thrombosis. In the following 2 cases, the intervening vasculature was
      resected along with the tumor, and the distal pedicles were anastomosed to their
      proximal counterparts using microvascular techniques. In addition to expediting
      resection of the tumor as well as allowing wider tumor resection margins, this
      technique also precludes thrombosis and subsequent flap loss.

PMID- 23123609
TI  - Lower lip reconstruction using a combined technique of the webster and johanson
      methods.
AB  - Oral reconstruction, especially with lower lip defects greater than 80% of the
      lip, is still challenging for plastic surgeons. Webster technique is mostly used
      for lower lip defects greater than 80% of the lip; however, resulting scars in
      the chin area (Schuchardt flap, a half-circle scar) are relatively conspicuous in
      Asian populations because of the trapdoor deformity. On the other hand, Johanson
      staircase flap technique, which is used to reconstruct lower lip defects of up to
      two thirds of the lip, results in relatively inconspicuous scarring and prevents
      trapdoor deformity. Thus, instead of Schuchardt flaps, we designed staircase
      flaps with a Webster technique. Two patients with lower lip carcinoma were
      operated on using this new technique. Large triangles of the skin and
      subcutaneous fat were removed from the nasolabial folds, and small staircases
      were removed from the lower lip to allow medial movement of the cheek tissues.
      The cosmetic and functional results were improved from the original Webster
      technique.

PMID- 23123610
TI  - Histological changes of the voice tube and possible clinical consequences after
      voice reconstruction with free ileocolon flap.
AB  - Free ileocolon flap has become a valid option for restoration of speech after
      pharyngolaryngectomy. After transfer, deprivation of the trophic intestinal
      contents and exposure to chronic intermittent airflow could substantially modify
      the structure of the voice tube, compromising its function. Biopsy specimens from
      14 voice tube segments were examined. Sections were evaluated after staining with
      hematoxylin-eosin, trichromic Masson, and antiproliferating cell nuclear antigen.
      In all samples, the mucosa displayed diffuse atrophy and decreased proliferation
      rate, and in some areas only a single layer of goblet cells and enterocytes was
      present. Erosions, ulcerations, and dysplastic changes were absent and the
      alterations were limited to the mucosal layer. None of the patients experienced
      problems related to the modifications of the mucosa. The changes detected in the
      voice tube mucosa seem to indicate a physiologic adaptation to the new
      environment as proved by disappearance of the chronic inflammatory infiltrate and
      absence of erosions when the steady state was reached.

PMID- 23123611
TI  - Salvage rates of compromised free flap breast reconstruction after recurrent
      thrombosis.
AB  - BACKGROUND: Microvascular complications after free flap breast reconstruction are
      devastating problems that increase patient morbidity and potentially lead to flap
      loss. Yet, there is a dearth of literature about rates of free flap salvage after
      recurrent vascular thromboses. METHODS: A retrospective review of all patients
      undergoing microvascular breast reconstruction at UCLA Medical Center from
      January 1991 to June 2010 was conducted. The incidence of microvascular
      thrombosis was evaluated and rates of flap salvage and complications were
      specifically analyzed after a single microvascular revision (Single Event), 2 or
      more revisions (Multiple Event), and delayed presentation (>2 days) with
      attempted salvage (Delayed Event). RESULTS: During the study period, 2094 free
      flap breast reconstructions were evaluated. Of these, 75 (3.6%) flaps suffered a
      microvascular complication and 16 (0.76%) flaps were lost. The overall salvage
      rate was 78.7% (59/75) with the highest salvage rate of 95.9% (47/49) for Single
      Events. Multiple Events had a salvage rate of 53.3% (8/15), whereas Delayed
      Events had a salvage rate of 27.3% (3/11). The salvage rate decreased with
      repeated microvascular events (P < 0.01). In the Multiple Event group, vascular
      conversion (alternate recipient vessel) correlated with improved flap salvage
      (87.5%), whereas the lack thereof was associated with flap loss (P < 0.001).
      CONCLUSIONS: The salvage rate of free flap breast reconstruction diminishes
      dramatically with recurrent microvascular complications, but can be improved with
      vascular conversion. The salvage rate in cases of delayed presentation is even
      worse confirming the need for vigilant postoperative monitoring and aggressive
      intervention in the setting of flap compromise.

PMID- 23123612
TI  - Presurgical orthopedic treatment ameliorates postoperative nasal deformity after
      cheiloplasty.
AB  - We assessed the postoperative nasal form and symmetry after presurgical use of a
      Hotz plate (HP) in patients with unilateral complete cleft lip and palate (UCLP).
      The subjects were 28 infants with UCLP who underwent cheiloplasty. Of these
      subjects, 14 underwent presurgical orthopedic treatment using the HP (HP group)
      and 14 underwent the same treatment without the HP (non-HP group). Photographic
      records were obtained 1 and 6 months after cheiloplasty, and the results of
      anthropometric analysis were compared between the 2 groups. The nasal inclination
      and the ratio of the width of the nasal base to the total width of the nose were
      significantly improved in the HP group compared with the non-HP group at both
      postoperative time points. Thus, presurgical use of the HP significantly improved
      the nasal asymmetry and deformity in UCLP patients after primary cheiloplasty and
      nasal repair. 

PMID- 23123613
TI  - Simultaneous contralateral reduction mammoplasty or mastopexy during unilateral
      free flap breast reconstruction.
AB  - BACKGROUND: After unilateral breast reconstruction, a procedure on the
      contralateral breast is often needed to achieve symmetry. However, there is no
      consensus regarding when to perform the contralateral balancing procedure. Here,
      we present a single surgeon's experience with performing contralateral symmetry
      procedures simultaneously with free flap autologous breast reconstruction.
      METHODS: We evaluated 77 consecutive patients (mean age, 50.5 years) who
      underwent abdominal-based free flap unilateral breast reconstruction and a
      simultaneous contralateral breast procedure performed by a single surgeon.
      RESULTS: Thirty-eight patients (49%) underwent immediate breast reconstruction,
      and 39 patients (51%) underwent delayed reconstruction. Forty patients (52%)
      received preoperative chemotherapy, and 31 (40%) received preoperative radiation
      therapy. Patients' mean body mass index was 28.3 kg/m. The most common free flaps
      were the muscle-sparing transverse rectus abdominis myocutaneous flap (n = 53)
      and deep inferior epigastric perforator flap (n = 22). Contralateral procedures
      included reduction mammoplasty (n = 48, 62%) and mastopexy (n = 29, 38%). In 43
      patients (56%), breast reconstruction was completed after a single stage, and in
      34 patients (44%), revisions were performed (flap: n = 16, 21%; contralateral
      breast: n = 8, 10%; both breasts: n = 10, 13%). Mean follow-up for patients was
      53.2 months. At last follow-up, most patients had no evidence of disease (n = 68,
      88%), six patients (8%) had died of disease, 1 patient (1%) was alive with
      disease, and 2 patients (3%) had died of other causes. CONCLUSIONS: For patients
      who need contralateral reduction mammoplasty or mastopexy for symmetry,
      performing these procedures and breast reconstruction simultaneously facilitates
      single-stage breast reconstruction in most patients.

PMID- 23123614
TI  - Chest wall reconstruction for sternal dehiscence after open heart surgery.
AB  - BACKGROUND: Sternal dehiscence is a grave complication after open heart surgery.
      Sternal debridement and flap coverage are the mainstays of therapy, but no
      consensus exists regarding the appropriate level of debridement. More recently,
      the use of vacuum-assisted closure devices has been advocated as a bridge to
      definitive closure, but indications for use remain incompletely defined.
      MATERIALS AND METHODS: A retrospective review of all chest wall reconstructions
      performed from January 2000 to December 2010 was conducted. The type of operative
      management was evaluated to assess morbidity, mortality, and length of hospital
      stay. RESULTS: Fifty-four patients underwent chest wall reconstruction for
      poststernotomy mediastinitis. Of these patients, 24 underwent conservative
      sternal debridement with flap closure, 24 underwent radical sternectomy including
      resection of the costal cartilages followed by flap closure, and 6 underwent
      radical sternectomy with vacuum-assisted closure therapy followed by flap closure
      in a delayed fashion. There were 15 patients in the conservative group and 8
      patients in the radical sternectomy group who developed postoperative
      complications (62.5% vs 33.3%, P < 0.05). The conservative sternectomy group had
      more serious complications requiring reoperation compared to the radical
      sternectomy group (86.7% vs 25.0%, P < 0.05). The most common complication in the
      former group was flap dehiscence (8/15, 53.3%), whereas that in the latter group
      was a superficial wound infection (6/8, 75.0%). There was no significant
      difference in mortality (25.0% vs 25.0%, P > 0.05%) or length of hospital stay.
      CONCLUSIONS: Radical sternectomy including the costal cartilages is associated
      with lower rates of surgical morbidity and reoperation, but not mortality.

PMID- 23123615
TI  - Impact of prior ipsilateral chest wall radiation on pedicled TRAM flap breast
      reconstruction.
AB  - BACKGROUND: This study compares complication rates between transverse rectus
      abdominis myocutaneous (TRAM) flaps based on previously irradiated versus
      nonirradiated superior pedicles to assess the impact of prior ipsilateral chest
      wall radiation on pedicled TRAM flap breast reconstruction. METHODS: A
      retrospective study of 302 consecutive TRAM flap reconstructions was performed;
      76 TRAM flaps based on a previously irradiated superior epigastric pedicle were
      compared to 226 TRAM flaps based on a nonirradiated pedicle in medical
      comorbidities, oncologic data, and complications. RESULTS: Patients having
      undergone previous chest wall irradiation had a higher cancer stage, but
      demographic data were otherwise similar within the groups. Previous chest wall
      irradiation did not result in increased rate of flap loss, infection, and fat
      necrosis. However, there was a trend toward higher revision rate in the
      previously irradiated TRAM group. CONCLUSIONS: Previous radiation to the superior
      epigastric pedicle is not associated with a significant increase in flap
      complications and should be considered a viable modality for pedicled TRAM flap
      breast reconstruction.

PMID- 23123616
TI  - Rapamycin extends lifespan and delays tumorigenesis in heterozygous p53+/- mice.
AB  - TOR (Target of Rapamycin) pathway accelerates cellular and organismal aging.
      Similar to rapamycin, p53 can inhibit the mTOR pathway in some mammalian cells.
      Mice lacking one copy of p53 (p53+/- mice) have an increased cancer incidence and
      a shorter lifespan. We hypothesize that rapamycin can delay cancer in
      heterozygous p53+/- mice. Here we show that rapamycin (given in a drinking water)
      extended the mean lifespan of p53+/- mice by 10% and when treatment started early
      in life (at the age less than 5 months) by 28%. In addition, rapamycin decreased
      the incidence of spontaneous tumors. This observation may have applications in
      management of Li-Fraumeni syndrome patients characterized by heterozygous
      mutations in the p53 gene.

PMID- 23123617
TI  - Improving clinical leadership in stoma care.
AB  - Welcome to this year's second edition of the BJN stoma care supplement. This
      supplement coincides with our annual conference (WCET) this year to be held in
      the magnificent city of Edinburgh.

PMID- 23123618
TI  - Caring for vulnerable ostomists: learning disabilities and stoma care.
AB  - It is without doubt that people with learning difficulties are considered
      vulnerable and meeting the healthcare needs of this group in society is now
      recognised as a challenging task. This case study examines the implications of
      life with a stoma for one particular  man with learning difficulties and reflects
      on the key issues that have influenced his care: stigma and isolation, general
      healthcare needs for people with learning disabilities and the association with
      stoma care, and the provision of care and whose role it is. Key findings include
      inconsistencies between primary, secondary and social care, resulting in lack of
      integration and flexibility in provision of care; lack of responsibility for
      care, with a 'pass the buck' response; lack of knowledge about stoma care in most
      care settings; and, as a stoma care nurse, the importance of personal instinct,
      along with persistence in advocating appropriate levels of care for vulnerable
      ostomists.

PMID- 23123619
TI  - Quality of life after ileo-anal pouch formation: patient perceptions.
AB  - This article describes a qualitative study, exploring the experiences of six
      individuals who have undergone an ileo-anal pouch formation and their subsequent
      lifestyle after this reconstructive surgical procedure. The aim of this study was
      to ascertain whether individuals who had an ileo-anal pouch believed themselves
      to have a good quality of life and a lifestyle that was not compromised as a
      result of surgery. The themes that emerged through the interviews were common to
      several participants and reflected their life, the decisions they were required
      to make and the resources available in order for them to do so. The outcome of
      this study, using a phenomenological approach, highlights that some individuals
      restrict their lifestyle, while others do not and are prepared to live with the
      consequences. The literature overwhelmingly concludes that the ileo-anal pouch
      procedure is a safe and efficient procedure with high patient satisfaction and
      good functional outcome, which should be recommended as a long-term option for
      ulcerative colitis and familial adenomatous polyposis sufferers. However, some
      patients curtail their lifestyle by restricting diet, altering meal patterns and
      minimising social activities to maintain day-to-day living with an ileo-anal
      pouch.

PMID- 23123620
TI  - What we know now: pouch surgery 40 years on.
AB  - For many patients, ileal pouch-anal anastomosis (also called ileo-anal pouch
      surgery) not only eradicates disease but also preserves the anal sphincter,
      enabling the patient to defecate in the normal way. Pouch surgery is approaching
      40 years and within this time has become the 'gold standard' in surgical
      management for ulcerative colitis and familial adeomatous polyposis. Much of the
      research over the years has explored surgical techniques and pouch function,
      failure and satisfaction, as well as long-term follow-up; however, some pouch
      problems continue to be a mystery. This short article aims to bring us up to date
      with what we know now that might have been beneficial to know then.

PMID- 23123621
TI  - Enhanced recovery and nurse-led telephone follow-up post surgery.
AB  - AIM: Nurse-led telephone follow-up was undertaken for patients after major
      colorectal surgery on the enhanced recovery programme following their discharge,
      with the aim of ensuring they were provided with adequate advice and information
      to enable their recovery at home. METHODOLOGY: A total of 200 patients were
      prospectively called within 4 weeks of discharge home from hospital by the
      enhanced recovery nurse. RESULTS: Diet was generally tolerated and mobility was
      continued at home. Many of the patients had seen a health professional since
      their discharge home for issues such as wound care or stoma review. Readmission
      rates were low and most concerns that patients reported were addressed during the
      telephone call. DISCUSSION: It is reassuring that the majority of patients were
      coping well and many of the concerns reported were simply addressed over the
      telephone with advice. After the first 100 patients were telephoned, improvements
      were made to the discharge advice provided to the second 100 patients. The
      responses suggest that there were less community nurse visits in the second half
      of the patient cohort and this may be associated with changes made to discharge
      advice. CONCLUSION: Patients continue to recover well once discharged home
      following colorectal surgery on the enhanced recovery pathway. Nurse-led
      telephone follow-up may be a suitable method for short-term follow-up and,
      potentially, it is also suitable for long-term follow-up of select groups of
      cancer patients.

PMID- 23123622
TI  - Dietary advice for patients  with a stoma.
AB  - In the enormity of stomal surgery, dietary advice for patients is key to
      rehabilitation. Yet it is too often overlooked (Porrett and Joels, 1996) and
      patients are given conflicting advice. These patients desperately want to do what
      is right. They want to recover, get well and go home. They are therefore happy to
      follow instructions, but need to understand the rationale for them. The author
      believes that dietary advice is invaluable and should be offered to all new stoma
      patients. She also believes that, if dietary advice is presented before and after
      surgery, in a clear and concise manner, it will equip patients for life with
      their stoma. Having knowledge brings power and patients are emplowered with a
      good knowledge base. The formation of a stoma disrupts the normal functioning of
      the gastrointestinal tract and alters its reabsorptive process, not to mention
      its flow. Initially, having a stoma is daunting and, for the vast majority of
      patients, terrifying. Patients need advice from ward or stoma nurses that will
      give them the confidence to make independent food choices. This, however, takes
      time, patience and lots of reiteration. Both verbal and written information are
      helpful. This article sets out to provide an understanding of ostomists' dietary
      needs to allow healthcare professionals to provide information with confidence,
      as and when required.

PMID- 23123623
TI  - Peristomal sore skin: assessing  the effect of an alginate wafer.
AB  - Peristomal skin problems affect a significant number of ostomists leading to
      problems with skin integrity and pouch adherence. This can begin to have a very
      negative impact on an ostomist's quality of life. The case studies within this
      article look at the use of an integral skin healing dressing, alginate, within
      the flange of a stoma bag and its effect on skin healing and patient quality of
      life. The patients and stoma care nurses have kindly agreed to allow their
      experiences to be published-all patients are anonymous.

PMID- 23123624
TI  - The human somatosensory system: from perception to decision making.
AB  - Pioneering human and animal research has yielded a better understanding of the
      brain networks involved in somatosensory perception and decision making. New
      methodical achievements in combination with computational formalization allow
      research questions to be addressed which increasingly reflect not only the
      complex sensory demands of real environments, but also the cognitive ones. Here,
      we review the latest research on somatosensory perception and decision making
      with a special focus on the recruitment of supplementary brain networks which are
      dependent on the situation-associated sensory and cognitive demands. We also
      refer to literature on sensory-motor integration processes during visual decision
      making to delineate the complexity and dynamics of how sensory information is
      relayed to the motor output system. Finally, we review the latest literature
      which provides novel evidence that other everyday life situations, such as
      semantic decision making or social interactions, appear to depend on tactile
      experiences; suggesting that the sense of touch, being the first sense to develop
      ontogenetically, may essentially support later development of other conceptual
      knowledge.

PMID- 23123625
TI  - PARM-1 promotes cardiomyogenic differentiation through regulating the BMP/Smad
      signaling pathway.
AB  - PARM-1, prostatic androgen repressed message-1, is an endoplasmic reticulum (ER)
      molecule that is involved in ER stress-induced apoptosis in cardiomyocytes. In
      this study, we assessed whether PARM-1 plays a role in the differentiation of
      stem cells into cardiomyocytes. While PARM-1 was not expressed in
      undifferentiated P19CL6 embryonic carcinoma cells, PARM-1 expression was induced
      during cardiomyogenic differentiation. This expression followed expression of
      mesodermal markers, and preceded expression of cardiac transcription factors.
      PARM-1 overexpression did not alter the expression of undifferentiated markers
      and the proliferative property in undifferentiated P19CL6 cells. Expression of
      cardiac transcription factors during cardiomyogenesis was markedly enhanced by
      overexpression of PARM-1, while expression of mesodermal markers was not altered,
      suggesting that PARM-1 is involved in the differentiation from the mesodermal
      lineage to cardiomyocytes. Furthermore, overexpression of PARM-1 induced BMP2
      mRNA expression in undifferentiated P19CL6 cells and enhanced both BMP2 and BMP4
      mRNA expression in the early phase of cardiomyogenesis. PARM-1 overexpression
      also enhanced phosphorylation of Smads1/5/8. Thus, PARM-1 plays an important role
      in the cardiomyogenic differentiation of P19CL6 cells through regulating BMP/Smad
      signaling pathways, demonstrating a novel role of PARM-1 in the cardiomyogenic
      differentiation of stem cells.

PMID- 23123626
TI  - Salinomycin, a polyether ionophoric antibiotic, inhibits adipogenesis.
AB  - The polyether ionophoric antibiotics including monensin, salinomycin, and
      narasin, are widely used in veterinary medicine and as food additives and growth
      promoters in animal husbandry including poultry farming. Their effects on human
      health, however, are not fully understood. Recent studies showed that salinomycin
      is a cancer stem cell inhibitor. Since poultry consumption has risen sharply in
      the last three decades, we asked whether the consumption of meat tainted with
      growth promoting antibiotics might have effects on adipose cells. We showed in
      this report that the ionophoric antibiotics inhibit the differentiation of
      preadipocytes into adipocytes. The block of differentiation is not due to the
      induction of apoptosis nor the inhibition of cell proliferation. In addition,
      salinomycin also suppresses the transcriptional activity of the CCAAT/enhancer
      binding proteins and the peroxisome proliferator-activated receptor gamma. These
      results suggest that the ionophoric antibiotics can be exploited as novel anti
      obesity therapeutics and as pharmacological probes for the study of adipose
      biology. Further, the pharmacological effects of salinomycin could be a harbinger
      of its toxicity on the adipose tissue and other susceptible target cells in
      cancer therapy.

PMID- 23123627
TI  - Smaller quantal size and faster kinetics of single exocytotic events in
      chromaffin cells from the APP/PS1 mouse model of Alzheimer's disease.
AB  - The kinetics of single-amperometric exocytotic events has been measured in
      chromaffin cells of C57 mice and in an APP/PS1 mouse model of Alzheimer's disease
      (AD). K(+) depolarisation causes a burst of spikes that indicate the quantal
      release of the single-vesicle content of catecholamine. The kinetic analysis of
      278 spikes from 10 control cells and 520 spikes from 18 APP/PS1 cells shows the
      following features of the latter compared with the former: (i) 45% lower t(1/2);
      (ii) 60% smaller quantal size; (iii) 50% lower decay time. Spike feet also showed
      60% smaller quantal size. Immunofluorescence and thioflavin staining showed no
      amyloid beta (Abeta) burden in adrenal medulla slices of APP/PS1 mice that
      however exhibited dense Abeta plaques in the cortex and hippocampus. Furthermore,
      acetylcholinesterase staining of adrenal medulla indicated no apparent
      differences in the innervation by splanchnic cholinergic nerve terminals of
      chromaffin cells from control and APP/PS1 mice. This is the first report
      identifying subtle differences in the last steps of exocytosis that could be an
      indication of synaptic dysfunction of the secretory machinery not linked to Abeta
      burden in AD.

PMID- 23123628
TI  - Nitric oxide depletion alters hematopoietic stem cell commitment toward
      immunogenic dendritic cells.
AB  - BACKGROUND: NO* is a key molecule involved in the regulation of cell survival,
      proliferation and differentiation in many cell types. In this study we
      investigated the contribution of NO* during the differentiation of human
      peripheral blood hemopoietic stem cells (CD34+HSCs) toward immunogenic dendritic
      cells (i-DCs). METHODS: We depleted autocrine NO* production, using NG-monomethyl
      L-arginine monoacetate (L-NMMA) and paracrine NO', using oxy-hemoglobin (HbO2) as
      a NO* scavenger during in vitro differentiation of CD34+HSCs to i-DCs. We
      monitored the NO* level, cell proliferation, phenotype and differentiation
      potential. RESULTS: We found that the depletion of paracrine or autocrine NO*
      correlated with (I) an active proliferation state at the end of differentiation,
      when control cells were not proliferating; (II) a significant reduction in the
      expression levels of differentiative markers (CD1a and HLA-DR) with a parallel
      high expression of the CD34 marker (III) with a retrieved clonogenic ability
      compared to control cells. CONCLUSIONS: On the whole, our data indicate that the
      depletion of NO* during the commitment stage blocks CD34+HSC differentiation into
      i-DCs and maintains an undifferentiated, highly proliferating cell population,
      indicating/revealing a novel role for NO* in the commitment of CD34+HSCs into i
      DCs. GENERAL SIGNIFICANCE: The essential finding of the present study is that
      NO*, produced in HSCs by NOS enzymes, may act as autocrine and paracrine
      effectors regulating the in vitro differentiation process of CD34+-HSCs toward i
      DCs.

PMID- 23123629
TI  - Role of JNK and p38 MAPK in Taiwanin A-induced cell death.
AB  - AIM: The lignan compound Taiwanin A is cytotoxic for human cancer cells. Taiwanin
      A has been previously shown to damage microtubules, induce mitotic arrest and
      cause apoptosis in cancer cells. The goal of the current study is to identify
      intracellular signaling pathways that are involved in Taiwanin A-mediated
      apoptosis. MAIN METHODS: We examined the activation of three mitogen-activated
      protein kinases (MAPKs), extracellular signal-regulated kinase (ERK), p38 and c
      Jun N-terminal kinase (JNK), in HepG2 cells after Taiwanin A treatment. The role
      of MAPK activation in Taiwanin A-induced apoptosis was examined using Western
      blotting, caspase activity assays combined with specific MAPK inhibitors and
      shRNA treatment to knockdown JNK. KEY FINDINGS: Taiwanin A activated all three
      MAPKs (ERK, p38 and JNK). Cytotoxicity was blocked by the p38 MAPK inhibitor
      SB203580 and the JNK inhibitor SP600125 but not by the ERK inhibitor PD98059. A
      combined treatment of SB203580 and SP600125 showed increased effects on the
      inhibition of Taiwanin A cytotoxicity, suggesting that both JNK and p38 play a
      role in Taiwanin A-induced apoptosis. Inhibition of p38 activity reduced Taiwanin
      A-induced p53 phosphorylation on Ser15. Direct interaction of Taiwanin A
      activated p38 and p53 was demonstrated by immunoprecipitation. In addition,
      inhibition of JNK by SP600125 or silencing of the JNK scaffold protein JIP2
      reduced phosphorylation of Bcl-2, which may help to promote anti-apoptotic
      pathways. SIGNIFICANCE: We demonstrated for the first time that two distinct
      apoptotic pathways, the p38-p53 and JNK-Bcl-2 pathways, were triggered by the
      anti-microtubule compound Taiwanin A.

PMID- 23123630
TI  - Cytogenetic status of healthy children assessed with the alkaline comet assay and
      the cytokinesis-block micronucleus cytome assay.
AB  - In the present study the alkaline comet assay and the cytokinesis-block
      micronucleus cytome (CBMN Cyt) assay were used to evaluate the baseline frequency
      of cytogenetic damage in peripheral blood lymphocytes (PBLs) of 50 healthy
      children from the general population in Croatia (age, 11.62+/-1.81 years). Mean
      values of tail length, tail intensity and tail moment, as comet assay parameters,
      were 12.92+/-0.10, 0.73+/-0.06 and 0.08+/-0.01, respectively. The mean frequency
      of micronuclei (MN) for all subjects was 2.32+/-0.28 per 1000 bi-nucleated cells,
      while the mean frequency of nucleoplasmic bridges (NPBs) was 1.72+/-0.24 and of
      nuclear buds (NBUDs) 1.44+/-0.19. The mean nuclear division index (NDI) was
      1.70+/-0.05. When comet-assay parameters were considered, higher mean values for
      all three were found for the female population. According to the Mann-Whitney U
      test applied on the results of the comet assay, the only statistically
      significant difference between the male and female populations was found for tail
      length. Similar to the results obtained by the comet assay, girls showed higher
      mean values of all three measured parameters of the CBMN Cyt assay. This
      difference was statistically significant for total number of NPBs only. In the
      case of the NDI, a higher mean value was also obtained in girls, but this
      difference was not statistically significant. The results obtained present
      background data that could be considered as normal values for healthy children
      living in urban areas, and can later on serve as baseline values for further
      toxicological monitoring. Additionally, the usefulness of both techniques in
      measuring cytogenetic damage during bio-monitoring of children is confirmed.

PMID- 23123631
TI  - Cyclometalated iridium(III) polypyridine dibenzocyclooctyne complexes as the
      first phosphorescent bioorthogonal probes.
AB  - We report the synthesis, photophysical behavior, and biological properties of new
      cyclometalated iridium(iii) polypyridine complexes appended with a
      dibenzocyclooctyne (DIBO) moiety; these complexes have been utilized as the first
      phosphorescent bioorthogonal probes for azide-modified biomolecules.

PMID- 23123632
TI  - Has brain imaging discovered anything new about how the brain works?
AB  - There have now been roughly 130,000 papers on fMRI. While these have clearly
      contributed to our understanding of the functional anatomy of the human brain, it
      is less clear that they have changed the way in which we think about the brain.
      The issue, in other words, is whether they have established new principles about
      how the brain works. In this paper we offer as an example one new principle,
      partly to lay down the criteria that are required for establishing a new
      principle, and partly to encourage others to offer other principles. Our example
      concerns the flexible flow of information through the cortex that must occur
      according to the demands of the task or current context. We suggest that this
      flexibility is achieved by feedback connections from the prefrontal and parietal
      cortex, and that these include connections to sensory and motor areas. However,
      the nature of the selective effect differs. The parietal cortex can select both
      within and across processing streams. By across streams we mean that it can have
      the same influence on different streams, for example the dorsal and ventral
      visual systems. However, only the prefrontal cortex can also select between
      processing streams. The difference between the prefrontal and parietal effects is
      due to their different positions within the processing hierarchy. 

PMID- 23123634
TI  - CIK cells from recurrent or refractory AML patients can be efficiently expanded
      in vitro and used for reduction of leukemic blasts in vivo.
AB  - Autologous cytokine-induced killer (CIK) cell transfusion may prevent tumor
      relapse in acute myeloid leukemia (AML). This study investigated whether CIK
      cells from recurrent or refractory AML patients with high peripheral leukemia
      cell burdens could be expanded to a clinically usable number, and it further
      evaluated the antitumor potentials in vitro and in vivo. The numbers and
      phenotypes of CIK cells expanded from nine AML patients and 10 healthy donors
      were compared. Cytotoxicity (against K562 and U937 cell lines) and cytokine
      secretion (interleukin-2, interferon-gamma, tumor necrosis factor-alpha and
      vascular endothelial growth factor) were tested for AML-derived and healthy donor
      derived CIK cells and fresh peripheral blood mononuclear cells from healthy
      donors. Importantly, we assessed the therapeutic effects of autologous CIK cell
      infusions in two patients with AML. The proportions of CD3(+)and CD3(+)CD56(+)
      CIK cells from patients with AML were similar to those from healthy donors, and
      the number of CD3(+)CD56(+) cells in AML-derived CIK cells was expanded
      approximately 1,020-fold. Phenotype analyses with flow cytometry showed that the
      leukemic cells were gradually eliminated during the process of CIK cell
      preparation to an almost undetectable level. Although the cytotoxic effect of AML
      derived CIK cells was equivalent to that of healthy donors, AML-derived CIK cells
      had a significantly higher cytokine-secreting capacity. In clinical treatment,
      the leukemia burden in the peripheral blood of one patient was dramatically
      decreased after four transfusions within 4 months. CIK cells can be efficiently
      expanded in vitro from patients with recurrent or refractory AML and may be used
      for reduction of leukemic blasts in vivo.

PMID- 23123633
TI  - The neural basis of non-native speech perception in bilingual children.
AB  - The goal of the present study is to reveal how the neural mechanisms underlying
      non-native speech perception change throughout childhood. In a pre-attentive
      listening fMRI task, English monolingual and Spanish-English bilingual children -
      divided into groups of younger (6-8yrs) and older children (9-10yrs) - were asked
      to watch a silent movie while several English syllable combinations played
      through a pair of headphones. Two additional groups of monolingual and bilingual
      adults were included in the analyses. Our results show that the neural mechanisms
      supporting speech perception throughout development differ in monolinguals and
      bilinguals. While monolinguals recruit perceptual areas (i.e., superior temporal
      gyrus) in early and late childhood to process native speech, bilinguals recruit
      perceptual areas (i.e., superior temporal gyrus) in early childhood and higher
      order executive areas in late childhood (i.e., bilateral middle frontal gyrus and
      bilateral inferior parietal lobule, among others) to process non-native speech.
      The findings support the Perceptual Assimilation Model and the Speech Learning
      Model and suggest that the neural system processes phonological information
      differently depending on the stage of L2 speech learning.

PMID- 23123635
TI  - Oxygen saturation after birth in preterm infants treated with continuous positive
      airway pressure and air: assessment of gender differences and comparison with a
      published nomogram.
AB  - AIMS: The goal of the study was to compare preductal SpO2 in the first 10 min
      after birth in preterm infants treated with non-invasive continuous positive
      airway pressure (CPAP) and air with a published nomogram of preductal SpO2 in
      preterm infants who received no medical intervention, and to examine gender
      differences. DESIGN: Prospective observational study. PATIENTS AND METHODS: We
      enrolled infants of <=32 weeks gestation who were spontaneously breathing with
      heart rate >100 bpm, and treated with face mask CPAP and air during postnatal
      stabilisation. SpO2 limits were targeted at >=75% at 5 min and >=85% at 10 min
      and heart rate at >100 bpm. FIO2 was titrated against SpO2. Preductal SpO2,
      airway pressure and FIO2 were recorded with a data acquisition system from birth
      until stabilisation. Babies receiving supplemental oxygen (>21%), positive
      pressure ventilation, were intubated and/or received chest compressions or drugs
      were excluded. RESULTS: Measurements were obtained in 102 babies with median
      gestational age of 29 (range: 24-31) weeks. Median SpO2 was significantly higher
      in the observational group than in the reference range at 3 min (82% (CI 71% to
      85%) vs 76% (CI 67% to 83%); p<0.05), at 4 min (87% (CI 81% to 90%) vs 81% (CI
      72% to 88%); p<0.05), at 5 min (92% (CI 88% to 95%) vs 86% (CI 80% to 92%);
      p<0.05), at 6 min (94% (CI 90% to 97%) vs 90% (CI 81% to 95%); p<0.05), at 7 min
      (95% (CI 92% to 97%) vs 92% (CI 85% to 95%); p<0.05), at 8 min (96% (CI 93% to
      98%) vs 92% (CI 87% to 96%); p<0.05) and at 9 min (97% (CI 92% to 99%) vs 93% (CI
      87% to 96%); p<0.05). Female babies achieved targeted SpO2 significantly earlier
      than male babies. CONCLUSIONS: Preterm babies receiving CPAP and air and
      especially female subjects achieve reference oxygen saturation more rapidly than
      spontaneously breathing preterm babies without respiratory aid.

PMID- 23123636
TI  - Oesophageal lung.

PMID- 23123637
TI  - Longitudinal assessment of endothelial function in the microvasculature of mice
      in-vivo.
AB  - Endothelial dysfunction is associated with early development of cardiovascular
      disease, making longitudinal measurements desirable. We devised a protocol using
      laser Doppler imaging (LDI) and iontophoresis of acetylcholine (ACh) and sodium
      nitroprusside (SNP) to assess the skin microcirculation longitudinally in mice
      every 4 weeks for 24 weeks in two groups of C57BL/6 mice, chow versus high
      cholesterol diet(known to induce endothelial dysfunction). LDI measurements were
      compared with vascular function (isometric tension) measured using wire myography
      in the tail artery in response to ACh and SNP. Microvascular responses to ACh
      were significantly reduced in cholesterol-fed versus chow-fed mice from week 4
      onwards (P<0.005, ANOVA). Pre-treatment with N(G)-nitro-L-arginine methyl-ester
      hydrochloride (L-NAME) showed a significant reduction in ACh response compared
      with vehicle-treated animals (P<0.05) at baseline and at 12 weeks. In cholesterol
      fed mice, ACh responses were 226 +/- 21 and 180 +/- 21 AU (P=0.03) before and
      after L-NAME, respectively. A reduction in ex-vivo ACh response was detected in
      the tail artery in cholesterol-fed mice, and a significant correlation found
      between peak microvascular ACh response and maximum ACh response in the tail
      artery (r=0.699, P=0.017). No changes were found in SNP responses in the
      microvasculature or tail artery. Using this protocol, we have shown longitudinal
      decreases in microvascular endothelial function to cholesterol feeding. L-NAME
      studies confirm that the reduced vasodilatation to ACh in cholesterol-fed mice
      was mediated partly through reduced NO bioavailability. Wire myography of tail
      arteries confirmed that in-vivo measurements of microvascular function reflect ex
      vivo vascular function in other beds. Longitudinal assessments of skin
      microvascular function in mice could provide a useful translatable model for
      assessing early endothelial dysfunction.

PMID- 23123639
TI  - A novel effect of imidazole derivative KK-42 on increasing survival of Aeromonas
      hydrophila challenged prawn Macrobrachium nipponense.
AB  - Imidazole derivative KK-42 is well known as the insect growth regulator. Here we
      find that KK-42 pretreatment could promote the survival of Macrobrachium
      nipponense infected with Aeromonas hydrophila, which is considered to be possibly
      related to the prophenoloxidase (proPO), a conserved copper-containing enzyme
      that plays an important role in defense against pathogens. In this study, a full
      length of proPO gene from M. nipponense haemocytes, designated as MnproPO, was
      firstly cloned and characterized. The full-length cDNA contained 2428 bp with a
      2013 bp open reading frame encoding a putative proPO protein of 671 amino acids
      with a predicted molecular mass of 76.5 kDa and pI of 7.31. It was predicted to
      possess all the expected features of proPO members, including two putative copper
      binding sites with six histidine residues and a thiol ester-like motif. Sequence
      analysis showed that MnproPO exhibited the highest amino acid sequence similarity
      (93%) to a proPO of Macrobrachium rosenbergii. The gene was expressed highly in
      haemocytes and weakly in hepatopancreas. Real-time PCR analysis revealed that the
      MnproPO expression increased significantly at 3, 12 and 24 h after KK-42
      treatment, the PO activity also importantly rose from 6 to 48 h in KK-42-treated
      prawns and reached the maximum at 24 h with a 2.3-fold higher than that in
      control group. Injection of A. hydrophila could stimulate the MnproPO
      transcription and PO activity whether or not the prawns were pretreated by KK-42,
      the mRNA level increased obviously only at 3 h and 6 h after the bacterium
      injection (challenged control), but increased constantly during the phase of
      experiment except at 6 h under the condition of KK-42 pretreatment (challenged
      treatment group). The change trend of PO activity was basically similar to that
      of MnproPO expression. Our present results demonstrate that the MnproPO
      expression as well as PO activity may be induced by KK-42, which is likely one of
      the molecular mechanisms of KK-42 acts for increasing survival of the prawn
      infected with A. hydrophila.

PMID- 23123638
TI  - The anticancer agent YC-1 suppresses progestin-stimulated VEGF in breast cancer
      cells and arrests breast tumor development.
AB  - Recent epidemiological studies show that postmenopausal women taking estrogen
      progestin hormone replacement therapy (HRT) have a higher risk of breast cancer
      than women on an HRT regimen lacking progestins. This may be related to the
      observation that progestin-treated breast cancer cells express and secrete high
      levels of vascular endothelial growth factor (VEGF), a potent angiogenic factor
      that promotes breast tumor growth. Anti-progestins such as RU-486 block this
      effect, indicating that progesterone receptors (PR) are involved in promoting
      VEGF induction; however antiprogestins cross-react with other steroid receptors
      which limits their clinical use. Alternative strategies are, therefore, needed to
      arrest the growth of progestin-dependent tumors. 3-(5'-hydroxymethyl-2'-furyl)-1
      benzylindazole (YC-1), a novel anticancer drug initially developed as an
      inhibitor of HIF-1alpha, is currently undergoing preclinical trials against
      various forms of cancer. Since HIF-1alpha has recently been implicated in PR
      mediated VEGF synthesis, we undertook studies to determine whether YC-1 inhibits
      progestin-dependent VEGF induction and tumor progression. Surprisingly, we found
      that YC-1 downregulated PR in human breast cancer cells, both in vivo and in
      vitro, thereby blocking progestin-dependent induction of VEGF and tumor growth.
      YC-1 also inhibited progestin-accelerated DMBA-induced mammary tumors in rats,
      properties which would likely render it effective against progestin-dependent
      tumors which frequently develop in post-menopausal women. We, therefore, propose
      that based on our observations, YC-1 warrants further investigation as a novel
      agent which could prove extremely useful as an anti-angiogenic chemotherapeutic
      drug.

PMID- 23123640
TI  - Shrimp Dscam and its cytoplasmic tail splicing activator serine/arginine (SR)
      rich protein B52 were both induced after white spot syndrome virus challenge.
AB  - The serine/arginine (SR)-rich protein family is phylogenetically conserved and
      plays significant roles in mRNA maturation, including alternative splicing (AS).
      In Drosophila, SR protein B52 functions as a splicing activator to regulate AS
      events in several genes, including the Down syndrome cell adhesion molecule
      (Dscam). In this study, the B52 gene from Litopenaeus vannamei (LvB52) was
      isolated and characterized. The open reading frame of LvB52 contains 1149 bp
      encoding 382 amino acids. The deduced LvB52 protein includes two RNA recognition
      motifs (RRM) at the N terminus and an arginine/serine rich domain (RS rich
      domain) at the C terminus, and thus shows the expected RRM1-RRM2-RS domain
      architecture. Tissue tropism analysis revealed that LvB52 is expressed in most
      tissues and at high levels in stomach and muscle. After white spot syndrome virus
      (WSSV) infection, a parallel increase in the expression of total LvDscam, tail
      less LvDscam, membrane-bound LvDscam and LvB52 was observed after 24 hpi.
      Conversely, there was no obvious change in the expression of the AS repressor
      Lvhrp36. In vivo dsRNA silencing of LvB52 induced element 3 exclusion in the
      LvDscam cytoplasmic tail, but no abnormal exclusions in the Ig2-Ig3 region or the
      transmembrane region. We also found that the exon of the Ig7 region was quite
      often excluded, even in normal shrimp, and that LvB52 silencing was associated
      with a decrease in the variability of this region. Taken together, our data
      suggest that LvB52 acts as a splicing activator that regulates AS events in
      LvDscam.

PMID- 23123641
TI  - The problem of non-superiority: what do we know after KOMET?

PMID- 23123642
TI  - The ARSACS phenotype can include supranuclear gaze palsy and skin lipofuscin
      deposits.

PMID- 23123643
TI  - Carbon fragmentation measurements and validation of the Geant4 nuclear reaction
      models for hadrontherapy.
AB  - Nuclear fragmentation measurements are necessary when using heavy-ion beams in
      hadrontherapy to predict the effects of the ion nuclear interactions within the
      human body. Moreover, they are also fundamental to validate and improve the Monte
      Carlo codes for their use in planning tumor treatments. Nowadays, a very limited
      set of carbon fragmentation cross sections are being measured, and in particular,
      to our knowledge, no double-differential fragmentation cross sections at
      intermediate energies are available in the literature. In this work, we have
      measured the double-differential cross sections and the angular distributions of
      the secondary fragments produced in the (12)C fragmentation at 62 A MeV on a thin
      carbon target. The experimental data have been used to benchmark the prediction
      capability of the Geant4 Monte Carlo code at intermediate energies, where it was
      never tested before. In particular, we have compared the experimental data with
      the predictions of two Geant4 nuclear reaction models: the Binary Light Ions
      Cascade and the Quantum Molecular Dynamic. From the comparison, it has been
      observed that the Binary Light Ions Cascade approximates the angular
      distributions of the fragment production cross sections better than the Quantum
      Molecular Dynamic model. However, the discrepancies observed between the
      experimental data and the Monte Carlo simulations lead to the conclusion that the
      prediction capability of both models needs to be improved at intermediate
      energies.

PMID- 23123644
TI  - Angiotensin II regulates the LARG/RhoA/MYPT1 axis in rat vascular smooth muscle
      in vitro.
AB  - AIM: To identify a key protein that binds monomeric G protein RhoA and activates
      the RhoA/Rho kinase/MYPT1 axis in vascular smooth muscle cells (VSMCs) upon
      angiotensin II (Ang II) stimulation. METHODS: Primary cultured VSMCs from Sprague
      Dawley rats were transfected with siRNAs against leukemia-associated RhoGEF
      (LARG), and then treated with Ang II, losartan, PD123319, or Val(5)-Ang II. The
      target mRNA and protein levels were determined using qPCR and Western blot
      analysis, respectively. Rat aortic rings were isolated, and the isometric
      contraction was measured with a force transducer and recorder. RESULTS:
      Stimulation with Ang II (0.1 MUmol/L) for 0.5 h significantly increased the level
      of LARG mRNA in VSMCs. At 3, 6, and 9 h after the treatment with Ang II (0.1
      MUmol/L) plus AT(2) antagonist PD123319 (1 MUmol/L) or with AT(1) agonist Val(5)
      Ang II (1 MUmol/L), the LARG protein, RhoA activity, and phosphorylation level of
      myosin phosphatase target subunit 1 (MYPT1) in VSMCs were significantly
      increased. Knockdown of LARG with siRNA reduced these effects caused by AT(1)
      receptor activation. In rat aortic rings pretreated with LARG siRNA, Ang II
      induced contraction was diminished. CONCLUSION: Ang II upregulates LARG gene
      expression and activates the LARG/RhoA/MYPT1 axis via AT(1), thereby maintaining
      vascular tone.

PMID- 23123645
TI  - [6]-Shogaol inhibits melanogenesis in B16 mouse melanoma cells through activation
      of the ERK pathway.
AB  - AIM: To investigate the effect of [6]-shogaol, an active ingredient in ginger, on
      melanogenesis and the underlying mechanisms. METHODS: B16F10 mouse melanoma cells
      were tested. Cell viability was determined with the MTT assay. Melanin content
      and tyrosinase activity were analyzed with a spectrophotometer. The protein
      expression of tyrosinase and microphthalmia associated transcription factor
      (MITF), as well as phosphorylated or total ERK1/2 and Akt were measured using
      Western blot. RESULTS: Treatment of the cells with [6]-shogaol (1, 5, 10 MUmol/L)
      reduced the melanin content in a concentration-dependent manner. [6]-Shogaol (5
      and 10 MUmol/L) significantly decreased the intracellular tyrosinase activity,
      and markedly suppressed the expression levels of tyrosinase and MITF proteins in
      the cells. Furthermore, [6]-shogaol (10 MUmol/L) activated ERK, which was known
      to negatively regulate melanin synthesis in these cells. Pretreatment with the
      specific ERK pathway inhibitor PD98059 (20 MUmol/L) greatly attenuated the
      inhibition of melanin synthesis by [6]-shogaol (10 MUmol/L). CONCLUSION: The
      results demonstrate that [6]-shogaol inhibits melanogenesis in B16F10 mouse
      melanoma cells via activating the ERK pathway.

PMID- 23123648
TI  - Advocacy - strengthening the foundation of caring.
AB  - Warm greetings from the United States! First, let me say that I am honoured to
      author a guest editorial in the British Journal of Nursing. When Ian Peate
      extended this kind invitation, I immediately considered what subject matter would
      be relevant to a UK nursing audience.

PMID- 23123647
TI  - N-Propionyl polysialic acid precursor enhances the susceptibility of multiple
      myeloma to antitumor effect of anti-NprPSA monoclonal antibody.
AB  - AIM: To study the antitumor effect of anti-NprPSA monoclonal antibody (mAb) in
      combination with ManNPr, a precursor of N-propionyl PSA, in multiple myeloma
      (MM), and to explore the mechanisms of the action. METHODS: Human multiple
      myeloma cell line RPMI-8226 was tested. The cells were pre-treated with ManNPr
      (1, 2, and 4 mg/mL), and then incubated with anti-NprPSA mAb (1 mg/mL). Cell
      apoptosis in vitro was detected using MTT assay and flow cytometry. BALB/c nude
      mice were inoculated sc with RPC5.4 cells. On 5 d after the injection, the mice
      were administered sc with anti-NprPSA mAb (200 MUg/d) and ManNPr (5 mg/d) for 8
      d. The tumor size and body weight were monitored twice per week. TUNEL assay was
      used for detecting apoptosis in vivo. The apoptotic pathway involved was examined
      using Western blot analysis and caspase inhibitor. RESULTS: Treatment of RPMI
      8226 cells with anti-NprPSA mAb alone failed to inhibit cell growth in vitro. In
      RPMI-8226 cells pretreated with ManNPr, however, the mAb significantly inhibited
      the cell proliferation, decreased the viability, and induced apoptosis, which was
      associated with cleavage of caspase-3, caspase-8, caspase-9, and poly(ADP-ribose)
      polymerase. In the mouse xenograft model, treatment with the mAb in combination
      with ManNPr significantly inhibited the tumor growth, and induced significant
      apoptosis as compared to treatment with the mAb alone. Moreover, apoptosis
      induced by the mAb in vivo resulted from the activation of the caspases and
      poly(ADP-ribose) polymerase. CONCLUSION: The anti-NprPSA mAb in combination with
      ManNPr is an effective treatment for in vitro and in vivo induction of apoptosis
      in multiple myeloma.

PMID- 23123646
TI  - Neuroprotective role of ATP-sensitive potassium channels in cerebral ischemia.
AB  - ATP-sensitive potassium (K(ATP)) channels are weak, inward rectifiers that couple
      metabolic status to cell membrane electrical activity, thus modulating many
      cellular functions. An increase in the ADP/ATP ratio opens K(ATP) channels,
      leading to membrane hyperpolarization. K(ATP) channels are ubiquitously expressed
      in neurons located in different regions of the brain, including the hippocampus
      and cortex. Brief hypoxia triggers membrane hyperpolarization in these central
      neurons. In vivo animal studies confirmed that knocking out the Kir6.2 subunit of
      the K(ATP) channels increases ischemic infarction, and overexpression of the
      Kir6.2 subunit reduces neuronal injury from ischemic insults. These findings
      provide the basis for a practical strategy whereby activation of endogenous
      K(ATP) channels reduces cellular damage resulting from cerebral ischemic stroke.
      K(ATP) channel modulators may prove to be clinically useful as part of a
      combination therapy for stroke management in the future.

PMID- 23123649
TI  - Intensive care through  the eyes of the patient.
AB  - As an experienced intensive-care unit (ICU) nurse, I have often spoken with my
      colleagues about patients' experiences, and also with patients of their
      experiences in ICU. It's fair to say I have never had a true understanding of
      this, until recently when I was admitted to the unit in which I work following a
      motorcycle accident.

PMID- 23123650
TI  - Effect of education on knowledge, skills and attitudes around pain.
AB  - AIMS: The purpose of this study was to assess the effectiveness of an acute pain
      educational programme in improving nurses' knowledge, skills and attitudes around
      postoperative pain management. BACKGROUND: Poor postoperative pain management is
      consistently reported as a problem for patients (Chung and Lui, 2003; Klopper et
      al, 2006; Bell and Duffy, 2009). This is often attributed to health
      professionals' lack of knowledge and access to training programmes, which have
      been cited as barriers to effective pain management (Wilkes et al, 2003; Dihle et
      al 2006). The Acute Pain Service (APS) team at HSE Mid-Western Regional Hospital,
      Limerick, and the Centre for Nurse and Midwifery Education developed a training
      programme for nurses in pain management based on the International Association
      for the Study of Pain (2005) curriculum for nurses. METHODS: A convenience sample
      of 59 nurses attending an educational programme on acute pain management was
      studied. Validated questionnaires were completed before, immediately after and 6
      weeks after the educational programme to assess knowledge and attitudes towards
      acute pain management. Nurses were also asked to rate their views on 18
      statements on acute pain management. RESULTS: The acute pain educational
      programme intervention improved nurses' knowledge and attitudes towards pain
      assessment and management (p<0.01). It was most effective immediately after the
      pain education programme. CONCLUSION: Continuing evidenced-based educational
      programmes in pain management can improve nurses' knowledge of pain. The results
      of this study could guide the development and implementation of continuing
      educational programmes for nursing staff in providing patients with evidence
      based pain management.

PMID- 23123651
TI  - Quality of life after percutaneous coronary intervention: part 1.
AB  - Quality of life (QOL) is a complex concept comprised of biopsychosocial,
      spiritual and environmental dimensions. However, the majority of research
      addresses only its physical function perspectives. This two-part series examines
      the holistic perspective of QOL of patients after percutaneous coronary
      intervention (PCI). Part 1 explains the research process of a cross-sectional
      descriptive study and its limitations. Data were collected by a mailed WHOQOL
      BREF questionnaire in Maltese from a systematic sample of patients who had
      undergone PCI; the response rate was 64% (n=228; males n=169, females n=59, age
      40-89 years). Part 1 also considers limitations, such as its cross-sectional
      design and retrospective data collection. The hierarchy of human needs theory
      (Maslow, 1999) guided the study. Part 2 gives the findings on the holistic view
      of QOL. Having social and family support, as a characteristic of Maltese culture
      appeared to contribute towards a better QOL.

PMID- 23123652
TI  - Patient and public involvement  to support liver disease research.
AB  - Patient and public involvement (PPI) has become increasingly important to ensure
      the needs of patients are fully considered when they participate in clinical
      trials. Most funders now require a plan for PPI in grant applications. When fully
      embraced and correctly implemented, PPI adds an important dimension to clinical
      trials, and its continuing development is critical if we are to maintain the
      public's support for clinical research. The development of a PPI panel for the
      National Institute for Health Research Birmingham Liver Biomedical Research Unit
      (NIHR BRU) has helped to: promote research locally and nationally; improve
      recruitment to and participation in trials; promote public engagement and
      education activities; and improve the quality and relevance of consent forms and
      information sheets for participants. The NIHR BRU has the support of a PPI panel
      which constantly champions the research being undertaken to the wider community.
      This paper describes how the panel was established and why it is so effective.

PMID- 23123653
TI  - Sporting for people  with a learning disability.
AB  - The 2012 Olympic Games in London have been raising awareness nationally about the
      importance of sport for everyone in the population (London Organising Committee
      of the Olympic Games and Paralympic Games Ltd, 2007), reminding us of the message
      delivered by the Department of Health's (DH) White Paper, Our health, our care,
      our say (DH, 2006), which placed an emphasis on the importance of prevention of
      ill health through healthy living.

PMID- 23123654
TI  - Olympic NHS tribute: a perfect close to a 39-year nursing career.
AB  - I have worked in the NHS for 39 years and now, it seems I have come full circle.

PMID- 23123655
TI  - The use of Resolor (prucalopride)  for chronic constipation in women.
AB  - Chronic constipation is a common problem among women, is associated with anxiety
      and depression and can adversely affect quality of life (Mason et al, 2002).
      Chronic constipation is often unrelieved by simple laxatives, dietary
      manipulation or lifestyle modification, with other specialist treatment options
      being invasive and often not widely available. More recently attention has turned
      to newer prokinetic agents, such as prucalopride (Resolor(r)), which increase gut
      motility and intestinal transit, for the relief of chronic constipation. While
      these are not effective for everyone, there is evidence that prucalopride can
      increase bowel frequency, relieve bothersome symptoms associated with
      constipation and improve quality of life for women who have failed to achieve
      satisfactory relief from two other laxatives (National Institute for Health and
      Clinical Excellence).

PMID- 23123656
TI  - Duty of confidence and the use  of social networking sites.
AB  - Social networking sites are a popular form of online communication used by an
      estimated 350000 registered nurses. The use of such sites by nurses must be done
      with caution because their duty of confidence extends to their online presence
      and inappropriate remarks or pictures posted online can call their fitness to
      practise into question. This article reviews the scope of a nurse's duty of
      confidence and discusses the requirements for the acceptable use of social
      networks by health professionals.

PMID- 23123657
TI  - Perspectives on quality improvement training.
AB  - John Tingle discusses a recent report by the Health Foundation on quality
      improvement for health professionals.

PMID- 23123658
TI  - Caring for our healthcare future: the Government White Paper.
AB  - The Government has published a White Paper on reforming care. The paper
      identifies some of the failures of the current system and suggests improvements.
      Professor Alan Glasper summarises the strategy and goals of the paper and
      considers the criticism from the RCN.

PMID- 23123659
TI  - The end is nigh... approaching graduation.
AB  - Adam Reilly is a student nurse and mentor. In his column, he writes about his
      approaching graduation and what the future holds for a newly qualified nurse. He
      also provided some tips for second and third year students on how to cope with
      the course and prepare for qualification.

PMID- 23123660
TI  - Teaching and learning: from staff nurse to nurse consultant. Part 6: planning a
      teaching session.
AB  - If you have been following this series on teaching and learning, you will begin
      to appreciate that teaching is far more than just standing in front of someone
      and telling them things.

PMID- 23123661
TI  - Lessons from the olympics.
AB  - Watching the Olympics this summer has been an inspiring experience. I am sure I
      am not alone in reflecting on what I can learn from it personally and, also, what
      I can learn in relation to my day-to-day work.

PMID- 23123662
TI  - Contributions of rat Ctr1 to the uptake and toxicity of copper and platinum
      anticancer drugs in dorsal root ganglion neurons.
AB  - Dorsal root ganglion (DRG) neurons are affected by platinum-induced neurotoxicity
      and neurodegenerative processes associated with disturbed copper homeostasis and
      transport. This study aimed to understand the role of copper transporter 1 (Ctr1)
      in the uptake and toxicity of copper and platinum drugs in cultured rat DRG
      neurons, and the functional activities of rat Ctr1 (rCtr1) as a membrane
      transporter of copper and platinum drugs. Heterologous expression of rCtr1 in
      HEK293 cells (HEK/rCtr1 cells) increased the uptake and cytotoxicity of copper,
      oxaliplatin, cisplatin and carboplatin, in comparison to isogenic vector
      transfected control cells. Cultured rat DRG neurons endogenously expressed rCtr1
      protein on their neuronal cell body plasma membranes and cytoplasm, and displayed
      substantial capacity for taking up copper, but were resistant to copper toxicity.
      The uptake of copper by both cultured rat DRG neurons and HEK/rCtr1 cells was
      saturable and inhibited by cold temperature, silver and zinc, consistent with it
      being mediated by rCtr1. Cultured rat DRG neurons accumulated platinum during
      their exposure to oxaliplatin and were sensitive to oxaliplatin cytotoxicity. The
      accumulation of platinum by both cultured rat DRG neurons and HEK/rCtr1 cells,
      during oxaliplatin exposure, was saturable and temperature dependent, but was
      inhibited by copper only in HEK/rCtr1 cells. In conclusion, rCtr1 can transport
      copper and platinum drugs, and sensitizes cells to their cytotoxicities. DRG
      neurons display substantial capacity for accumulating copper via a transport
      process mediated by rCtr1, but appear able to resist copper toxicity and use
      alternative mechanisms to take up oxaliplatin.

PMID- 23123663
TI  - Aminocoumarins inhibit osteoclast differentiation and bone resorption via
      downregulation of nuclear factor of activated T cells c1.
AB  - Aminocoumarins, such as coumermycin A1 and novobiocin, are natural products of
      streptomycetes. They are potent inhibitors of bacterial DNA gyrase and are used
      to suppress the growth of bacteria in inflammatory diseases. However, their
      effect in osteoclastogenesis has not been investigated. In this study, using
      mouse bone-marrow-derived macrophages (BMMs), we showed that coumermycin A1 and
      novobiocin suppressed receptor activator of nuclear factor-kappaB ligand (RANKL)
      induced osteoclast formation. The inhibitory effect of coumermycin A1 was
      associated with impaired activation of multiple signaling events downstream of
      RANK, including extracellular signal-regulated kinase, p38, and c-Jun terminal
      kinase phosphorylation, followed by decreased c-Fos and nuclear factor of
      activated T cells (NFAT)c1 expression. Ectopic overexpression of a constitutively
      active form of NFATc1 completely rescued the anti-osteoclastogenic effect of
      coumermycin A1, suggesting that the anti-osteoclastogenic effect of coumermycin
      A1 was mainly attributable to reduction in NFATc1 expression. Coumermycin A1 also
      abrogated RANKL-induced expression of interleukin-1beta, tumor necrosis factor
      alpha, and inducible nitric oxide synthase in mouse BMMs. Consistent with the in
      vitro anti-osteoclastogenic effect, the aminocoumarin suppressed
      lipopolysaccharide-induced osteoclast formation and bone loss in in vivo mouse
      experiments. Taken together, our data demonstrate that aminocoumarins inhibit
      osteoclast formation and bone resorption, and comprise a potential therapeutic
      strategy for treating bone destructive diseases.

PMID- 23123664
TI  - Elevation of cysteine consumption in tamoxifen-resistant MCF-7 cells.
AB  - Tamoxifen (TAM) resistance is a main cause of therapeutic failure in breast
      cancers. Although methionine dependency is a phenotypic characteristic of tumor
      cells, the role of sulfur amino acid metabolism in chemotherapy resistance
      remains to be elucidated. This study compared metabolite profiles of sulfur amino
      acid metabolism from methionine to taurine or glutathione (GSH) between normal
      MCF-7 and TAM-resistant MCF-7 (TAMR-MCF-7) cells. TAMR-MCF-7 cells showed
      elevated levels and activities of enzymes involved in both transsulfuration from
      methionine to cysteine and metabolism of cysteine to GSH and taurine. Cysteine
      concentrations in TAMR-MCF-7 cells and medium conditioned by cell culture for 42h
      were markedly decreased, while GSH, hypotaurine, and taurine concentrations in
      the medium were increased. These results show that TAMR-MCF-7 cells display
      enhanced cysteine utilization. The addition of propargylglycine, a specific
      cystathionine gamma-lyase inhibitor, and buthionine sulfoximine, a specific gamma
      glutamylcysteine ligase inhibitor, to TAMR-MCF-7 cells, but not to MCF-7 cells,
      resulted in cytotoxicity after sulfur amino acid deprivation. These results
      suggest that cell viability of TAMR-MCF-7 cells is affected by inhibition of
      sulfur amino acid metabolism, particularly cysteine synthesis from homocysteine
      and GSH synthesis from cysteine. Additionally, the S-adenosylmethionine/S
      adenosylhomocysteine ratio, an index of transmethylation potential, in TAMR-MCF-7
      cells increased to ~3.6-fold relative to that in MCF-7 cells, a finding that may
      result from upregulation of methionine adenosyltransferase IIa and S
      adenosylhomocysteine hydrolase. In conclusion, this study suggests that TAMR-MCF
      7 cells display enhanced cysteine utilization for synthesis of GSH and taurine,
      and are sensitive to inhibition of cysteine metabolism.

PMID- 23123665
TI  - Clinical outcomes of peritoneal dialysis patients transferred from hemodialysis:
      a matched case-control study.
AB  - OBJECTIVE: Our study aimed to evaluate clinical outcomes of patients transferred
      to peritoneal dialysis (PD) because of complications related to hemodialysis
      (HD). ? METHODS: In a 1:2 matched case-control study, we compared patient and
      technique survival between patients initially treated with HD for at least 3
      months and then transferred to PD (transfer group) and patients started on and
      continuing with PD (no-transfer group). ? RESULTS: All baseline characteristics
      except for initial residual urinary output were comparable between the groups.
      Compared with patients in the transfer group, patients in the no-transfer group
      had a higher initial daily residual urinary output [850 mL (range: 600 - 1250 mL)
      vs 0 mL (range: 0 - 775 mL/d), p = 0.000]. The main reasons for transfer to PD
      were vascular access problems and cardiovascular disease. Patient survival and
      technique failure rates did not significantly differ between the groups (p >
      0.05). The 1-, 3-, and 5-year patient survival rates were 80.0%, 53.7%, and 27.6%
      in the transfer group and 89.7%, 60.2%, and 43.1% in the no-transfer group. Age
      (per 10 years) and serum albumin were independent risk factors for long-term
      survival in PD patients. Relative risk of either death or technique failure was
      not significantly increased in patients transferred from HD. ? CONCLUSIONS:
      Patients who transferred to PD after failing HD had outcomes on PD similar to
      those for patients who started with and were maintained on PD. Age (per 10 years)
      and serum albumin were independent risk factors for long-term survival in PD
      patients.

PMID- 23123666
TI  - Peritoneal fibrosis and high transport are induced in mildly pre-injured
      peritoneum by 3,4-dideoxyglucosone-3-ene in mice.
AB  - Peritoneal dialysis (PD) solution contains high concentrations of glucose and
      glucose degradation products (GDPs). One of several GDPs--3,4-dideoxyglucosone-3
      ene (3,4-DGE)--was recently identified as the most reactive and toxic GDP in PD
      fluids. In vitro, 3,4-DGE has been shown to induce mesothelial cell damage;
      however, its role in peritoneal fibrosis in vivo remains unclear. In the present
      study, we intraperitoneally administered chlorhexidine gluconate (CG) for mild
      peritoneal injury, and we then injected 3,4-DGE [38 MUmol/L (low concentration)
      or 145 MUmol/L (high concentration)] 5 times weekly for 4 weeks. Significant
      thickening of the parietal peritoneal membrane was observed only when treatment
      with low or high concentrations of 3,4-DGE occurred after CG administration, but
      not when either CG or 3,4-DGE alone was given. The combination of CG and 3,4-DGE
      also caused upregulation of messenger RNA expression of transforming growth
      factor beta1, connective tissue growth factor, fibronectin, collagen type 1
      alpha1 chain, alpha smooth muscle actin (alpha-SMA), vascular endothelial growth
      factor 164, NADPH oxidase 1 and 4, p22phox, p47phox, and gp91phox in peritoneal
      tissue. Treatment with CG alone was sufficient to cause significant F4/80
      positive macrophage infiltration, appearance of alpha-SMA-positive cells, and
      vessel formation in the submesothelial layer. Addition of 3,4-DGE markedly
      enhanced those changes and induced apoptosis, mainly in leukocytes. The
      concentration of 3,4-DGE in the abdominal cavity declined more rapidly in CG
      treated mice than in PBS-treated mice. Peritoneal membrane permeability
      determined by peritoneal equilibration test showed high transport conditions in
      peritoneum treated with both CG and 3,4-DGE. These results indicate that, when
      mild peritoneal damage is already present, 3,4-DGE causes peritoneal thickening
      and fibrosis, resulting in deterioration of peritoneal membrane function.

PMID- 23123667
TI  - Ultrafiltration characteristics of glucose polymers with low polydispersity.
AB  - BACKGROUND: Icodextrin, a glucose polymer with a polydispersity [ratio of weight
      average molecular weight (Mw) to number-average molecular weight] of
      approximately 2.6, has been shown, compared with glucose, to provide superior
      ultrafiltration (UF) efficiency [ratio of UF to carbohydrate (CHO) absorbed] when
      used as an osmotic agent during a long-dwell peritoneal dialysis exchange. In an
      experimental rabbit model, we evaluated the effect of Mw on the UF and UF
      efficiency of glucose polymers with low polydispersity. METHODS: A crossover
      trial in female New Zealand White rabbits (2.20 - 2.65 kg) with surgically
      implanted peritoneal catheters evaluated two glucose polymers at nominal
      concentrations of 7.5 g/dL: a 6K polymer (Mw: 6.4 kDa; polydispersity: 2.3) and a
      19K polymer (Mw: 18.8 kDa; polydispersity: 2.0). Rabbits were randomized to
      receive either the 6K (n = 11) or the 19K (n = 12) solution during the first
      exchange (40 mL/kg body weight). The alternative solution was evaluated in a
      second exchange 3 days later. During each 4-hour dwell, the UF and total glucose
      polymer CHO absorbed were determined. RESULTS: The UF was higher for the 6K (p <
      0.0001) than for the 19K polymer (mean +/- standard deviation: 73.6 +/- 30.8 mL
      vs. 43.0 +/- 20.2 mL), as was the amount of CHO absorbed (42.5% +/- 9.8% vs.
      35.7% +/- 11.0%, p = 0.021). In spite of higher CHO absorption, an approximately
      50% higher (p = 0.029) UF efficiency was achieved with the 6K polymer (28.3 +/-
      18.8 mL/g) than with the 19K polymer (19.0 +/- 11.3 mL/g). The results were
      independent of the order of the experimental exchanges. CONCLUSIONS: Glucose
      polymers with low polydispersity are effective osmotic agents in a rabbit model.
      The low-Mw polymer was more effective at generating UF and had a higher UF
      efficiency, but those results came at the expense of the polymer being more
      readily absorbed from the peritoneal cavity.

PMID- 23123668
TI  - Perspectives of patients, families, and health care professionals on decision
      making about dialysis modality--the good, the bad, and the misunderstandings!
AB  - OBJECTIVES: This study explored the factors influencing decision-making about
      dialysis modality, integrating the perspectives of patients, their families, and
      health care professionals within an Asian population. The study further sought to
      understand the low penetration rate of peritoneal dialysis (PD) in Singapore. ?
      METHODS: A sample of 59 participants comprising pre-dialysis patients, dialysis
      patients, caregivers, and health care professionals (HCPs) participated in semi
      structured interviews to explore the decision-making process and their views
      about various dialysis modalities. Data were thematically analyzed using NVivo9
      (QSR International, Doncaster, Australia) to explore barriers to and facilitators
      of various dialysis modalities and decisional support needs. ? RESULTS: Fear of
      infection, daily commitment to PD, and misperceptions of PD emerged as barriers
      to PD. Side effects, distance to dialysis centers, and fear of needling and pain
      were barriers to hemodialysis (HD). The experiences of other patients,
      communicated informally or opportunistically, influenced the preferences and
      choices of patients and family members for a dialysis modality. Patients and
      families value input from HCPs and yet express strong needs to discuss subjective
      experiences of life on dialysis (PD or HD) with other patients before making a
      decision about dialysis modality. ? CONCLUSIONS: Pre-dialysis education should
      expand its focus on the family as the unit of care and should provide
      opportunities for interaction with dialysis patients and for peer-led learning.
      Barriers to PD, especially misperceptions and misunderstandings, can be targeted
      to improve PD uptake.

PMID- 23123669
TI  - Acute peritoneal dialysis in neonates with acute kidney injury and hypernatremic
      dehydration.
AB  - OBJECTIVE: We aimed to evaluate the efficacy of acute peritoneal dialysis (PD)
      and clinical outcomes in neonates with acute kidney injury (AKI) and
      hypernatremic dehydration. ? METHODS: The medical records of 15 neonates with AKI
      and hypernatremic dehydration who were treated with acute PD were reviewed. The
      diagnoses were AKI with hypernatremic dehydration with or without sepsis in 13
      patients and AKI with hypernatremia and congenital nephropathy in 2 patients. The
      main indications for PD were AKI with some combination of oligoanuria, azotemia,
      hyperuricemia, and metabolic acidosis unresponsive to initial intensive medical
      treatment. ? RESULTS: The mean age of the patients at dialysis initiation was
      11.9 +/- 9 days, and the mean duration of PD was 6.36 +/- 4.8 days. In 7 patients
      (46.7%), hypotension required the use of vasopressors, and in 6 patients (40%),
      mechanical ventilation was required. Peritoneal dialysis-related complications
      occurred in 7 patients (46.7%), the most common being catheter malfunction (n =
      6). Four episodes of peritonitis occurred in the 15 patients (26.7%), 2 episodes
      in patients with congenital renal disease and 2 episodes in patients with sepsis
      and multiorgan failure, who did not survive. Congenital renal disease,
      septicemia, and the need for mechanical ventilation were important factors
      influencing patient survival. All patients with no pre-existing renal disease or
      sepsis recovered their renal function and survived. ? CONCLUSIONS: In neonates
      with AKI and hypernatremic dehydration, PD is safe and successful, and in
      patients without congenital renal disease or sepsis, the prognosis is good.
      Peritoneal dialysis should be the treatment of choice in neonates with AKI and
      hypernatremic dehydration who do not respond to appropriate medical treatment.

PMID- 23123671
TI  - Microfluidic synthesis of atto-liter scale double emulsions toward ultrafine
      hollow silica spheres with hierarchical pore networks.
AB  - A facile PDMS-glass hybrid microfluidic device is developed for generating
      uniform submicrometer-scale double emulsion droplets with unprecedented
      simplicity and controllability. Compared with planar flow-focusing geometries,
      our three-dimensional flow-focusing geometry is advantageous for stably producing
      femto- to atto-liter droplets without the retraction problem of the dispersed
      phase fluid. In addition, this microfluidic platform can withstand the use of
      strong organic solvents (e.g. tetrahydrofuran (THF) and toluene) as a dispersed
      phase without deforming PDMS devices because the dispersed phase containing
      organic solvents does not directly contact the PDMS wall. In particular,
      monodisperse double emulsions are generated spontaneously via the internal phase
      separation of single emulsions driven by the diffusion of a co-solvent
      (tetrahydrofuran) in microfluidic devices. Finally, we demonstrated that the
      double emulsions can be used as morphological templates of ultrafine spherical
      silica capsules with controlled hierarchical pore networks via the evaporation
      induced self-assembly (EISA) method. During EISA, triblock copolymers (Pluronic
      F127) act as a surfactant barrier separating the internal droplet from the
      continuous oil phase, resulting in the 'inverse' morphology (i.e. hydrophobic
      polymer-in-water-in-oil emulsions). Depending on the precursor composition and
      kinetic condition, various structural and morphological features, such as
      mesoporous hollow silica spheres with a single central core, multi-cores, or a
      combination of these with robust controllability can be seen. Electron microscopy
      (SEM, STEM, HR-TEM), small angle X-ray scattering (SAXS), and N(2) adsorption
      desorption confirm the well-controlled hierarchical pore structure of the
      resulting particles.

PMID- 23123670
TI  - Neutral solution low in glucose degradation products is associated with less
      peritoneal fibrosis and vascular sclerosis in patients receiving peritoneal
      dialysis.
AB  - BACKGROUND: The effects of novel biocompatible peritoneal dialysis (PD) solutions
      on human peritoneal membrane pathology have yet to be determined. Quantitative
      evaluation of human peritoneal biopsy specimens may reveal the effects of the new
      solutions on peritoneal membrane pathology. ? METHODS: Peritoneal specimens from
      24 PD patients being treated with either acidic solution containing high-glucose
      degradation products [GDPs (n = 12)] or neutral solution with low GDPs (n = 12)
      were investigated at the end of PD. As controls, pre-PD peritoneal specimens,
      obtained from 13 patients at PD catheter insertion, were also investigated. The
      extent of peritoneal fibrosis, vascular sclerosis, and advanced glycation end
      product (AGE) accumulation were evaluated by quantitative or semi-quantitative
      methods. The average densities of CD31-positive vessels and podoplanin-positive
      lymphatic vessels were also determined. ? RESULTS: Peritoneal membrane fibrosis,
      vascular sclerosis, and AGE accumulation were significantly suppressed in the
      neutral group compared with the acidic group. The neutral group also showed lower
      peritoneal equilibration test scores and preserved ultrafiltration volume. The
      density of blood capillaries, but not of lymphatic capillaries, was significantly
      increased in the neutral group compared with the acidic and pre-PD groups. ?
      CONCLUSIONS: Neutral solutions with low GDPs are associated with less peritoneal
      membrane fibrosis and vascular sclerosis through suppression of AGE accumulation.
      However, contrary to expectation, blood capillary density was increased in the
      neutral group. The altered contents of the new PD solutions modified peritoneal
      membrane morphology and function in patients undergoing PD.

PMID- 23123672
TI  - Pigeons show near-optimal win-stay/lose-shift performance on a simultaneous
      discrimination, midsession reversal task with short intertrial intervals.
AB  - Discrimination reversal tasks have been used as a measure of species flexibility
      in dealing with changes in reinforcement contingency. The simultaneous
      discrimination, midsession reversal task is one in which one stimulus (S1) is
      correct for the first 40 trials of an 80-trial session and the other stimulus
      (S2) is correct for the remaining trials. After many sessions of training with
      this task, pigeons show a curious pattern of choices. They begin to respond to S2
      well before the reversal point (they make anticipatory errors) and they continue
      to respond to S1 well after the reversal (they make perseverative errors). That
      is, they appear to be using the passage of time or number of trials into the
      session as a cue to reverse. We tested the hypothesis that these errors resulted
      in part from a memory deficit (the inability to remember over the intertrial
      interval, ITI, both the choice on the preceding trial and the outcome of that
      choice) by manipulating the duration of the ITI (1.5, 5, and 10 s). We found
      support for the hypothesis as pigeons with a short 1.5-s ITI showed close to
      optimal win-stay/lose-shift accuracy.

PMID- 23123673
TI  - Electrocardiographic PR lengthening and QRS widening- what else should we learn
      from such simple information?

PMID- 23123674
TI  - Community detection of long QT syndrome with a clinical registry: an alternative
      to ECG screening programs?
AB  - BACKGROUND: Long QT syndrome (LQTS) prevalence is estimated at 4 of 10,000 based
      on community electrocardiogram (ECG) screening, about which there is disagreement
      regarding efficacy, accuracy, cost-effectiveness, and practicality. Family
      studies of autosomal dominant conditions such as LQTS have revealed 8-9 gene
      positive family members per proband. OBJECTIVE: To evaluate a cardiac/genetic
      registry and family screening program as a tool to identify LQTS in the
      community. METHODS: Possible LQTS probands were referred to the New Zealand
      Cardiac Inherited Disease service. The registry was first established in the
      northern region (population 2.03 million), including central Auckland (population
      0.46 million). After clinical evaluation, genetic testing and family cascade
      screening were initiated. Genotype-positive individuals were classified as
      definite LQTS, and others were classified as definite or probable LQTS by
      clinical and ECG criteria. RESULTS: One hundred twelve probands were identified
      (presentation: 7 sudden death, 82 cardiac event, 16 ECG abnormality, and 7 sudden
      death of a family member). Following cascade screening, 309 patients with LQTS
      were identified (248 definite and 61 probable). Two hundred twenty patients had
      LQTS-causing mutations identified (120 [55%] LQT1, 78 [35%] LQT2, 19 [9%] LQT3, 1
      [0.5%] LQT 5, and 2 [1%] LQT7). Thus far, an average of 2.1 definitely or
      probably affected family members have been identified per proband. The community
      detection rate is 1.5 of 10,000 for the whole region and 2.2 of 10,000 in
      Auckland. CONCLUSIONS: A high level of community detection of LQTS is possible
      using a clinical registry. With adequate resourcing, this has the potential to be
      an effective alternative to community ECG screening.

PMID- 23123675
TI  - An impulsively controlled pest management model with n predator species and a
      common prey.
AB  - This paper investigates the dynamics of a competitive single-prey n-predators
      model of integrated pest management, which is subject to periodic and impulsive
      controls, from the viewpoint of finding sufficient conditions for the extinction
      of prey and for prey and predator permanence. The per capita death rates of prey
      due to predation are given in abstract, unspecified forms, which encompass large
      classes of death rates arising from usual predator functional responses, both
      prey-dependent and predator-dependent. The stability and permanence conditions
      are then expressed as balance conditions between the cumulative death rate of
      prey in a period, due to predation from all predator species and to the use of
      control, and to the cumulative birth rate of prey in the same amount of time.
      These results are then specialized for the case of prey-dependent functional
      responses, their biological significance being also discussed.

PMID- 23123676
TI  - Biomolecular computation with molecular beacons for quantitative analysis of
      target nucleic acids.
AB  - Molecular beacons are efficient and useful tools for quantitative detection of
      specific target nucleic acids. Thanks to their simple protocol, molecular beacons
      have great potential as substrates for biomolecular computing. Here we present a
      molecular beacon-based biomolecular computing method for quantitative detection
      and analysis of target nucleic acids. Whereas the conventional quantitative
      assays using fluorescent dyes have been designed for single target detection or
      multiplexed detection, the proposed method enables us not only to detect multiple
      targets but also to compute their quantitative information by weighted-sum of the
      targets. The detection and computation are performed on a molecular level
      simultaneously, and the outputs are detected as fluorescence signals.
      Experimental results show the feasibility and effectiveness of our weighted
      detection and linear combination method using molecular beacons. Our method can
      serve as a primitive operation of molecular pattern analysis, and we demonstrate
      successful binary classifications of molecular patterns made of synthetic
      oligonucleotide DNA molecules.

PMID- 23123677
TI  - The kinase activity of EphA4 mediates homeostatic scaling-down of synaptic
      strength via activation of Cdk5.
AB  - Neurons within a network have the ability to homeostatically scale-down their
      excitatory synaptic strength under conditions of persistent neuronal activity
      elevation, a process pivotal to neural circuit stability. How this homeostatic
      regulation is achieved at the molecular level in developing neural circuits,
      which face gradually elevated neuronal activity as part of circuit wiring, is not
      well-understood. Using dissociated hippocampal neuronal cultures, we identified a
      critical and cell autonomous role for the receptor tyrosine kinase EphA4 in
      mediating activity-induced homeostatic down-regulation of excitatory synaptic
      strength. Reducing the endogenous level of EphA4 in individual neurons by RNAi
      effectively blocked activity-induced scaling-down of excitatory synaptic
      strength, while co-transfection of RNAi resistant EphA4 rescued this effect.
      Furthermore, interfering with EphA4 forward signaling using EphA4-Fc blocked
      activity-induced homeostatic synaptic scaling-down, while direct activation of
      EphA4 with its ligand EphrinA1 weakened excitatory synaptic strength. Up- or down
      regulating EphA4 function in individual neurons also did not affect the density
      of excitatory synapses. The kinase activities of EphA4 and its downstream
      effector Cdk5 were both required for homeostatic synaptic scaling, as
      overexpression of EphA4 with constitutively active kinase activity reduced
      excitatory synaptic strength, while interfering with either the kinase activity
      of EphA4 or Cdk5 blocked activity-induced synaptic scaling. Consistently, the
      activities of EphA4 and Cdk5 increased significantly during global and persistent
      activity elevation. Together, our work demonstrated that the kinase activity of
      EphA4, via activation of downstream Cdk5 activity, mediates the scaling-down of
      excitatory synaptic strength under conditions of global activity elevation.

PMID- 23123678
TI  - Ionic liquid-derived charged polymers to show highly thermoresponsive LCST-type
      transition with water at desired temperatures.
AB  - A polymerised ionic liquid (poly(IL)) having suitable hydrophobicity undergoes a
      strongly temperature-sensitive LCST-type phase transition with pure water and
      also with aqueous salt solution, and the resulting hydrated poly(IL) further
      undergoes a sharp and reversible liquid-to-gel transition at ambient
      temperatures.

PMID- 23123680
TI  - Statistical analysis of longitudinal neuroimage data with Linear Mixed Effects
      models.
AB  - Longitudinal neuroimaging (LNI) studies are rapidly becoming more prevalent and
      growing in size. Today, no standardized computational tools exist for the
      analysis of LNI data and widely used methods are sub-optimal for the types of
      data encountered in real-life studies. Linear Mixed Effects (LME) modeling, a
      mature approach well known in the statistics community, offers a powerful and
      versatile framework for analyzing real-life LNI data. This article presents the
      theory behind LME models, contrasts it with other popular approaches in the
      context of LNI, and is accompanied with an array of computational tools that will
      be made freely available through FreeSurfer - a popular Magnetic Resonance Image
      (MRI) analysis software package. Our core contribution is to provide a
      quantitative empirical evaluation of the performance of LME and competing
      alternatives popularly used in prior longitudinal structural MRI studies, namely
      repeated measures ANOVA and the analysis of annualized longitudinal change
      measures (e.g. atrophy rate). In our experiments, we analyzed MRI-derived
      longitudinal hippocampal volume and entorhinal cortex thickness measurements from
      a public dataset consisting of Alzheimer's patients, subjects with mild cognitive
      impairment and healthy controls. Our results suggest that the LME approach offers
      superior statistical power in detecting longitudinal group differences. 

PMID- 23123681
TI  - Neurocognitive processing of body representations in artistic and photographic
      images.
AB  - Visual art because of its artistic context can be related to the general idea of
      providing alternative perceptual experiences. However, research examining the
      neural basis of art beyond the paradigm of beauty has been neglected. This study
      seeks to determine how the perception of a body in an artwork can be
      distinguished from the perception of a body in a non-artistic photography. While
      viewing different body representations in both artworks and photographs, subjects
      were required to evaluate the appeal of the portrayed persons. By using
      functional magnetic resonance imaging (fMRI) we show that the perception of a
      body within the context of art leads to a higher activation in the right parietal
      cortex and the extrastriate cortex bilaterally. Relating this result to concepts
      from previous research, we suggest that the perception of art is linked to visuo
      spatial coding and also motor mapping. In contrast, the higher activity in the
      ventromedial prefrontal cortex and the primary visual cortex during the
      perception of a body in a non-artistic frame of reference, i.e. in a photograph,
      can be linked to processes of person evaluation. Possibly, the task to judge the
      appeal of a person in a photograph might be more daunting and, thus, cause
      emotional and even moral challenges being reflected in the ventromedial
      prefrontal activity. Taken together, perceptual experiences within an artistic
      vs. a non-artistic frame of reference are based on distinct patterns of neuronal
      activity. 

PMID- 23123683
TI  - Effect of inhomogeneity in a patient's body on the accuracy of the pencil beam
      algorithm in comparison to Monte Carlo.
AB  - The pencil beam algorithm (PBA) is reasonably accurate and fast. It is,
      therefore, the primary method used in routine clinical treatment planning for
      proton radiotherapy; still, it needs to be validated for use in highly
      inhomogeneous regions. In our investigation of the effect of patient
      inhomogeneity, PBA was compared with Monte Carlo (MC). A software framework was
      developed for the MC simulation of radiotherapy based on Geant4. Anatomical sites
      selected for the comparison were the head/neck, liver, lung and pelvis region.
      The dose distributions calculated by the two methods in selected examples were
      compared, as well as a dose volume histogram (DVH) derived from the dose
      distributions. The comparison of the off-center ratio (OCR) at the iso-center
      showed good agreement between the PBA and MC, while discrepancies were seen
      around the distal fall-off regions. While MC showed a fine structure on the OCR
      in the distal fall-off region, the PBA showed smoother distribution. The fine
      structures in MC calculation appeared downstream of very low-density regions.
      Comparison of DVHs showed that most of the target volumes were similarly covered,
      while some OARs located around the distal region received a higher dose when
      calculated by MC than the PBA.

PMID- 23123684
TI  - Triggering memory recovery: effects of direct and incidental cuing.
AB  - The present study examined forgetting and recovery of narrative passages varying
      in emotional intensity, using what we refer to as the "dropout" method. Previous
      studies of this dropout procedure have used word lists as to-be-remembered
      material, but the present experiments used brief story vignettes with one-word
      titles (e.g., "Torture", "Insects"). These vignettes showed a strong dropout
      forgetting effect in free recall. Both text and picture cues from the vignettes
      eliminated the forgetting effect on a subsequent cued recall test. Vignette
      related pictures in an incidental picture naming task, however, triggered little
      recovery of initially forgotten vignettes, as shown on a post-test. The results
      extend findings of large forgetting and memory recovery effects to materials that
      are more naturalistic than word lists. The findings also show that picture cues,
      which trigger strong memory recovery effects on a direct test of memory, had
      little effect on recovery when cues were encountered incidentally.

PMID- 23123682
TI  - Making data sharing work: the FCP/INDI experience.
AB  - Over a decade ago, the fMRI Data Center (fMRIDC) pioneered open-access data
      sharing in the task-based functional neuroimaging community. Well ahead of its
      time, the fMRIDC effort encountered logistical, sociocultural and funding
      barriers that impeded the field-wise instantiation of open-access data sharing.
      In 2009, ambitions for open-access data sharing were revived in the resting state
      functional MRI community in the form of two grassroots initiatives: the 1000
      Functional Connectomes Project (FCP) and its successor, the International
      Neuroimaging Datasharing Initiative (INDI). Beyond providing open access to
      thousands of clinical and non-clinical imaging datasets, the FCP and INDI have
      demonstrated the feasibility of large-scale data aggregation for hypothesis
      generation and testing. Yet, the success of the FCP and INDI should not be
      confused with widespread embracement of open-access data sharing. Reminiscent of
      the challenges faced by fMRIDC, key controversies persist and include participant
      privacy, the role of informatics, and the logistical and cultural challenges of
      establishing an open science ethos. We discuss the FCP and INDI in the context of
      these challenges, highlighting the promise of current initiatives and suggesting
      solutions for possible pitfalls. 

PMID- 23123685
TI  - The person in the mirror: using the enfacement illusion to investigate the
      experiential structure of self-identification.
AB  - How do we acquire a mental representation of our own face? Recently, synchronous,
      but not asynchronous, interpersonal multisensory stimulation (IMS) between one's
      own and another person's face has been used to evoke changes in self
      identification (enfacement illusion). We investigated the conscious experience of
      these changes with principal component analyses (PCA) that revealed that while
      the conscious experience during synchronous IMS focused on resemblance and
      similarity with the other's face, during asynchronous IMS it focused on
      multisensory stimulation. Analyses of the identified common factor structure
      revealed significant quantitative differences between synchronous and
      asynchronous IMS on self-identification and perceived similarity with the other's
      face. Experiment 2 revealed that participants with lower interoceptive
      sensitivity experienced stronger enfacement illusion. Overall, self
      identification and body-ownership rely on similar basic mechanisms of
      multisensory integration, but the effects of multisensory input on their
      experience are qualitatively different, possibly underlying the face's unique
      role as a marker of selfhood.

PMID- 23123686
TI  - The hereditary predisposition to hip osteoarthritis and its association with
      abnormal joint morphology.
AB  - OBJECTIVE: Genetic factors and abnormalities of joint morphology are important in
      the aetiology of hip osteoarthritis (OA). The extent to which genetic influences
      are manifest through joint morphology has undergone limited investigation. Using
      a cohort with an hereditary predisposition to end-stage hip OA and a control
      group with no inherited risk, we aimed to identify associations with abnormal
      joint morphology and clinical features. DESIGN: One hundred and twenty-three
      individuals (mean age 52 years) with a family history of total hip arthroplasty
      (THA) (termed 'sibkids') were compared with 80 spouse controls. Morphology was
      assessed using standardised radiographs and cam, dysplasia, and pincer
      deformities defined. Regression modelling described the association of cohort
      with abnormal joint morphology, adjusting for confounders [age, gender, body mass
      index (BMI), OA, and osteophyte]. RESULTS: Sibkids had an odds ratio of 2.1
      [95%confidence interval (CI) 1.3-3.5] for cam deformity. There were no
      differences in the prevalence of dysplasia or pincer deformities. In both groups,
      hips with cam deformities or dysplasia were more likely to have clinical features
      than normal hips [odds ratio (OR) 4.46 (1.8-11.3), and 4.40 (1.4-14.3)
      respectively]. Pincer deformity was associated with positive signs in the sibkids
      but not in the controls (OR 3.0; 1.1-8.2). DISCUSSION: After adjustment for
      confounders that cause secondary morphological change, individuals with an
      hereditary predisposition to end-stage hip OA had a higher prevalence of
      morphological abnormalities associated with hip OA. Sibkids were more likely to
      demonstrate clinical features in the presence of pincer deformity, suggesting
      that the genes are acting not only through abnormal morphology but also through
      other factors that influence the prevalence of pain.

PMID- 23123687
TI  - Features of missense/nonsense mutations in exonic splicing enhancer sequences
      from cancer-related human genes.
AB  - Missense/nonsense mutations, which are related to pathogenic conditions, are
      regarded as pathogenic mutations. The features of pathogenic mutations in gene
      coding regions are still unclear. To explore the pathogenic mutation features of
      human cancer-related genes, 1227 missense/nonsense mutations from 99 human cancer
      related genes were analyzed. We found that the mutability in exonic splicing
      enhancers (ESEs) is less than that outside ESEs. CpG sites are more enriched in
      ESEs than outside ESEs. Decrease of mutability in ESEs is much larger than that
      outside ESEs upon removal of CpG mutations since CpG is more mutable. In
      addition, the bases in ESEs are prone to undergo C->T/G->A mutations. What is
      more, mutations in ESEs were preferentially located within 50 nt flanking the
      short exons (<=250 nt), and tend to be of conservative type with minimum effect
      on the protein structure. Finally, nonsense mutation located in ESEs might be
      related to Nonsense Mediated Decay (NMD) pathway. In conclusion, this study
      explored the features of pathogenic mutations of human cancer-related genes.

PMID- 23123688
TI  - Amantadine for freezing of gait in patients with Parkinson disease.
AB  - BACKGROUND: Freezing of gait (FOG) is a common symptom in patients with advanced
      Parkinson's disease (PD) representing a major cause of disability and falls.
      Although the pathophysiology of FOG remains poorly understood, nondopaminergic
      pathways have been implicated. Treatment studies of levodopa and selegiline have
      shown limited benefit for FOG. Limited data suggest that amantadine, an N-methyl
      D-aspartate receptor antagonist, may be beneficial for FOG in PD. OBJECTIVE: To
      examine the relationship between treatment with oral amantadine and FOG in
      patients with PD. METHODS: We conducted a retrospective chart review of PD
      patients who received amantadine specifically for FOG and had a follow-up
      assessment of FOG. The primary outcome measure was self-reported effectiveness of
      amantadine (improvement, worsening, or no change in FOG) based on records from
      the follow-up assessment. RESULTS: Eleven patients with PD with median age of PD
      onset of 67 years (range, 51-84 years) and median Hoehn and Yahr stage 3 (range,
      2-4) met the study population selection criteria. Ten of 11 patients reported
      improvement in FOG after initiation of amantadine, whereas FOG worsened in one
      patient. Median amantadine dosage was 100 mg twice daily, and treatment duration
      was 20 months (range, 6-66 months). Four patients reported reduction in benefit
      after 4 months. Three patients reported adverse effects, including blurred
      vision, visual hallucinations, and peripheral edema; the latter 2 effects
      resulted in discontinuation of amantadine. CONCLUSION: Amantadine is associated
      with self-reported improvement in FOG in PD, but this effect may be transient.
      Further studies, including a randomized placebo-controlled trial, are needed to
      better evaluate this association.

PMID- 23123689
TI  - Prevalence and pharmacological factors associated with impulse-control disorder
      symptoms in patients with Parkinson disease.
AB  - BACKGROUND: Impulse-control disorders (ICDs) occur in patients with Parkinson
      disease (PD), especially in younger patients on dopamine therapies. OBJECTIVE: To
      assess the prevalence of ICD symptoms and its pharmacological correlations in a
      sample of French patients with PD and without PD (poststroke). METHODS:
      Outpatients with PD and without PD (poststroke) were screened for compulsive
      behaviors related to hypersexuality, compulsive shopping, pathological gambling,
      or compulsive eating by means of the Questionnaire for Impulse-Control Disorders-
      short version. Full medical history and Unified Parkinson's Disease Rating Scale
      scores were also recorded. Dose of dopamine agonists were converted to defined
      daily doses (DDDs), according to the World Health Organization Anatomical
      Therapeutic Chemical classification system classification system. RESULTS: Two
      hundred three patients with PD and 52 patients without PD were recruited (mean +/
      SD age, 67 +/- 1 vs 69 +/- 2, P= 0.4; males: 62% vs 55% P= 0.2). Symptoms of
      ICDs were reported by 0% of poststroke patients and 25% of the patients with PD
      (P < 0.001). Hypersexuality was reported by 10% of the patients with PD,
      compulsive shopping by 6%, pathological gambling by 3%, and compulsive eating by
      14%. A logistic regression analysis found that age younger than 68 years (odds
      ratio [OR], 3.3; 95% confidence interval, 1.6-6.6) and exposure to dopamine
      agonists (OR, 20.3; 95% confidence interval, 2.7-65.0) or monoaminooxidase-B
      inhibitor (OR, 3.7; 95% confidence interval, 1.1-12.6) were significant factors
      associated with increased ICD frequency. Patients with ICD symptoms were exposed
      to higher dopamine doses than those without them (1.6 +/- 0.1 vs 1.0 +/- 0.1
      daily-defined doses; P < 0.001). A dose-response pharmacodynamic model disclosed
      a significant nonlinear dose-response relationship between dopamine agonists and
      frequency of ICD symptoms (P < 0.01). CONCLUSIONS: Impulse-control disorder
      symptoms were more frequent in the patients with PD than in the poststroke
      patients with PD. Impulse-control disorder symptoms were related to younger age
      and exposure to monoaminooxidase-B inhibitors, and showed a nonlinear dose
      response relationship with dopamine agonists.

PMID- 23123690
TI  - Clinical experience of dose conversion ratios between 2 botulinum toxin products
      in the treatment of cervical dystonia.
AB  - OBJECTIVES: The units of different botulinum toxin products are not identical,
      and the dose equivalence has been debated for several years. In the year 2000,
      our clinic changed the recommended botulinum toxin product from Botox to Dysport
      for the treatment of cervical dystonia. Based on published reports, where dose
      conversion ratios from 1:1 to 1:6 (Botox:Dysport) had been used, and our own
      clinical experience, the dose conversion ratio was set to 1:2. The objective of
      this study was to retrospectively monitor the used doses of each product and the
      subsequent clinical effect. METHODS: A retrospective study, using casebook notes
      from 75 patients, was done to investigate treatment doses, subjective clinical
      effect, and the appearance of adverse events. RESULTS: The median dose conversion
      ratio that had been used at the product switch was 1:2.3 (Botox:Dysport). After
      clinical adjustment, the ratio was 1:2.1 at the next 3 treatments. There was a
      tendency for a more effective treatment and more adverse events after the product
      switch. A follow-up was performed 6.5 years later using casebook notes from 53 of
      the same patients. By this time, the doses had been reduced, and the median dose
      conversion ratio had decreased to 1:1.7 (Botox:Dysport). The adverse events
      reported at this point were fewer for the patients treated. CONCLUSIONS: In this
      study, the most appropriate dose conversion ratio to use when switching from
      Botox to Dysport was 1:1.7.

PMID- 23123691
TI  - Tolerability profile of clonidine in the treatment of adults with Tourette
      syndrome.
AB  - OBJECTIVE: Clonidine, an alpha-2 adrenergic agonist, has been used to treat
      Tourette syndrome (TS) for nearly 3 decades. This first-tier medication is
      especially recommended for children and adolescents with a combination of
      attention-deficit/hyperactivity disorder and mild tics. Although clonidine is
      thought to have a low rate of adverse effects (AEs), little is known about its
      tolerability profile in adult patients with TS. METHODS: This study investigated
      the prevalence and characteristics of AEs associated with clonidine through a
      retrospective chart review. We assessed 36 patients with TS (27 men; mean [SD]
      age, 24.6 +/- 13.9; range, 10-62 years), of whom 32 (88.8%) had comorbid
      conditions (most common: attention-deficit/hyperactivity disorder, n = 12;
      obsessive-compulsive disorder, n = 9). RESULTS: Seventeen patients (47.2%)
      experienced AEs. Eleven patients (30.5%) withdrew clonidine because of the
      severity of AE (n = 5) or absence (n = 4)/reduction (n = 2) in efficacy. The most
      commonly reported AEs were sedation and headache. In most cases, AEs were mild
      and occurred with higher starting doses. In 12 patients (70.6%) who also took
      other psychotropic medications, cotherapy could have been linked to the
      appearance of AE. CONCLUSIONS: Our findings suggest that clonidine is a safe and
      well-tolerated medication in the TS population. Adults with TS treated with this
      medication experience mild and relatively infrequent AE; high starting dose and
      polytherapy seem to be the only clinically relevant risk factors for AE
      development.

PMID- 23123692
TI  - Effectiveness of duloxetine for the treatment of chronic nonorganic orofacial
      pain.
AB  - OBJECTIVE: We examined the pain-relieving effect of duloxetine on chronic
      nonorganic orofacial pain (burning mouth syndrome and atypical odontalgia),
      considering the influence of baseline depressive symptoms. METHODS: In this study
      of 12 weeks, duloxetine was administered in a fixed-flexible dose of 20 to 40
      mg/d to 41 patients with burning mouth syndrome and/or atypical odontalgia. Pain
      was evaluated using the visual analog scale (VAS) at baseline and at 2, 4, 6, 8,
      10, and 12 weeks of treatment. Depressive symptoms were assessed using the
      Hamilton Depression Rating Scale at baseline and at 12 weeks of treatment.
      RESULTS: We analyzed the data from 29 patients who completed the study. The VAS
      score at 12 weeks of treatment was significantly lower than that at baseline. The
      time course of the VAS scores revealed its significant decrease from 2 weeks of
      treatment compared to the baseline score. To investigate the influence of
      baseline depressive symptoms on the pain-relieving effect of duloxetine, the
      subjects were divided into 2 groups based on the Hamilton Depression Rating Scale
      score on initial consultation: groups with (>=8) and without (<=7) depressive
      symptoms. Two-way repeated-measures analysis of variance revealed no significant
      interaction between time and initial presence or absence of depression. An
      additional intent-to-treat last-observation-carried-forward analysis including
      dropped-out patients revealed a similar result. CONCLUSION: Duloxetine
      significantly relieved chronic nonorganic orofacial pain. Its pain-relieving
      effect appeared from 2 weeks of treatment. Furthermore, the pain-relieving
      effects of duloxetine similarly appeared regardless of the presence or absence of
      baseline depressive symptoms.

PMID- 23123693
TI  - Breast nurse practitioner training and assessment: a proposed model.
AB  - The role of the breast nurse practitioner has been expanding in recent years and
      many breast units in the UK employ nurse practitioners to carry out a variety of
      clinical duties. Most of these involve diagnostic assessment of breast diseases
      and clinical breast examination. While most nurse practitioners have been trained
      by shadowing breast surgeons, working under supervision, and demonstrating a
      satisfactory concordance, in terms of clinical opinion with their clinical
      supervisors, there is a lack of literature describing a training programme that
      includes assessment. A proposed model including induction, training, assessment
      (using established tools from a medical school and Royal Surgical Colleges) and
      audit, with a competency-based 'sign-off', is described in this article and
      supported by the experience of a nurse practitioner who has been successfully
      trained in this way. The model can instil confidence and credibility to employers
      and the public, and can also be adapted and extended to other areas of clinical
      practice.

PMID- 23123694
TI  - Renal cell cancer: nurses' role  in prevention and management.
AB  - In both the UK and throughout Europe, more patients are presenting with renal
      cell cancer (RCC), also known as renal cell carcinoma or kidney cancer. The
      overall survival rate varies depending on tumour grade, nodal involvement and
      metastasis. For those with metastasis survival drops to 10%. This article
      explores the risk factors associated with RCC diagnosis and staging, treatments
      including drugs and procedures and the role of the nurse in diagnosis and
      accurate assessment. Nurses are ideally suited to consider the physical,
      functional, social, and emotional status of their patients In addition, it is
      essential that the nurse has an understanding of new pharmaceutical therapies,
      which have been licensed to treat RCC, and a sound knowledge of the possible side
      effects and nursing management associated with these drugs.

PMID- 23123695
TI  - Professional boundaries  when working with adolescents.
AB  - This article aims to explore the impact of breaking professional boundaries in
      nursing with a particular focus on the area of adolescent oncology nursing. It
      gives an overview of adolescent cancer and service provision followed by a brief
      discussion of some of the challenges in adolescence coupled with an outline of
      the concept of professional boundaries. A case study approach is used to
      demonstrate what happens when the boundaries are broken and this is followed by
      some discussion in relation to 'ways of helping'. These suggestions are broken
      down into specific activities, which may be beneficial to nurses and others
      working in this field. This discussion is supported by relevant literature from
      other professional groups. The article seeks to offer useful advice to
      practitioners who supervise recently qualified staff and to those who find
      themselves in this difficult situation.

PMID- 23123696
TI  - Use of this season's tools to improve cancer care.
AB  - The end of the summer in the professional cancer calendar always seems to signal
      the start of conference season, with many UK, European and international
      conferences taking place. Key conferences include those held by the International
      Society of Nursing in Cancer Care (ISNCC) in Prague this year, the European
      Society for Medical Oncology (ESMO) in Vienna, and the European Cancer Congress
      in Amsterdam, within the UK, October sees the joint United Kingdom Oncology
      Nursing Society (UKONS) and British Oncology Pharmacy Association (BOPA)
      conference at Harrogate.

PMID- 23123697
TI  - Cancer-related neuropathic  pain: pharmalogical options.
AB  - Based on recent estimates, approximately 320500 people were diagnosed with cancer
      in the UK in 2009 (Cancer Research UK, 2012). Cancer is a major public health
      problem and is becoming even more significant as the population grows, ages, and
      increasingly embraces cancer-causing habits such as smoking, poor diet, and
      physical inactivity.  Patients with cancer may experience acute and chronic pain
      as a consequence of their disease or as an outcome of its treatment. Extensive
      research findings indicate that cancer pain is a problem for many patients and
      that it is often undertreated (Breuer et al, 2011).

PMID- 23123698
TI  - Patient perspective: journey of a breast cancer survivor and her use of person
      centered thinking tools.
AB  - Patient perspective: journey of a breast cancer survivor and her use of person
      centered thinking tools.

PMID- 23123699
TI  - Early breast cancer: diagnosis, treatment and survivorship.
AB  - Breast cancer is the most common female cancer and globally remains a major
      public health concern. The diagnosis and treatment of breast cancer continues to
      develop. Diagnosis is now more precise, surgery is less mutilating and women now
      have the option of breast conserving therapy with better cosmesis, and without
      sacrificing survival. Radiotherapy is more targeted and the selection of patients
      for adjuvant chemotherapy is based not only on prognostic and predictive factors,
      but also on newer molecular profiling that will ensure that chemotherapy is given
      to the patients who need and respond to it. These developments all provide a more
      tailored approach to the treatment of breast cancer. Management now involves a
      multidisciplinary team approach in order to provide the highest standard of care
      for patients throughout their cancer journey from diagnosis through treatment and
      into follow-up care.

PMID- 23123700
TI  - Sorafenib and TRAIL have synergistic effect on hepatocellular carcinoma.
AB  - A multi-kinase inhibitor, sorafenib, was recently approved and is currently
      recommended for the treatment of advanced hepatocellular carcinoma (HCC).
      However, HCC treatment outcomes are still poor and necessitate improvement.
      Therefore, we investigated the influence of sorafenib in combination with each of
      cytotoxic chemotherapy agents, hypoxia or tumor necrosis factor (TNF)-related
      apoptosis-inducing ligand (TRAIL), on cytotoxicity to determine which is the
      better adjuvant. Additive cytotoxicity of sorafenib to chemotherapy agents,
      hypoxia and TRAIL, to HCC cells was assessed using cell viability assay.
      Intracellular levels of anti-apoptotic proteins were determined using western
      blot analysis. Activation of Wnt/beta-catenin signaling was assessed using a
      luciferase reporter gene assay. Sorafenib significantly and synergistically
      enhanced the cytotoxicity of TRAIL to HCC cells and 4',6-diamidino-2-phenylindole
      (DAPI) staining showed increased apoptosis among cells treated with sorafenib and
      TRAIL. This augmentation in cytotoxicity was derived from sorafenib-mediated
      downregulation of anti-apoptotic proteins. However, sorafenib did not enhance the
      cytotoxicity of chemotherapy agents (cisplatin, 5-FU or doxorubicin) or hypoxic
      treatment to HCC. Moreover, hypoxic treatment induced Wnt/beta-catenin signaling
      activation. Our data showed that in combination TRAIL and sorafenib had a
      synergistic cytokilling effect on HCC cells and that this effect derived from
      sorafenib-mediated downregulation of anti-apoptotic proteins.

PMID- 23123702
TI  - Effects of protein restriction during gestation and lactation on cell
      proliferation in the hippocampus and subventricular zone: functional
      implications. Protein restriction alters hippocampal/SVZ cell proliferation.
AB  - There is no consensus about the effects of protein restriction on neurogenesis
      and behavior. Here, for the first time, we evaluated the effects of protein
      restriction during gestation and lactation, on the two major neurogenic regions
      of the adult brain, the subgranular zone (SGZ) of the hippocampal dentate gyrus
      and the subventricular zone (SVZ), simultaneously. We also assessed different
      types of behavior relevant to each region. After mating, pregnant Wistar rats
      were divided into a control group (CG) that received a normal diet (20% protein);
      and a protein-restriction group (PRG) that received a low-protein diet (8%
      protein). After birth, the same diets were provided to the mother and pups until
      weaning, when some rats were analyzed and others received a normal-protein diet
      until adulthood. Different sets of rats were used for cellular and behavioral
      studies in juvenile or adult age. Brains were processed for immunohistochemistry
      anti-BrdU, anti-Ki67, or anti-pHisH3. Juvenile and adult rats from distinct
      litters also underwent several behavioral tests. Our data show that early protein
      restriction results in a reduction of hippocampal progenitors and deficits in
      object recognition during adult life. Moreover, longer periods of immobility in
      the tail suspension and in the forced swimming tests revealed that PRG rats show
      a depressive behavior at 21 days of age (P21) and in adulthood. Furthermore, we
      suggest that despite the reduced number/proliferation of neural stem cells (B
      and/or E cells) in SVZ there is a compensatory mechanism in which the progenitors
      (types C and A cells) proliferate in a higher rate, without affecting olfactory
      ability in adulthood.

PMID- 23123701
TI  - Phospholipase C mediates (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane
      (DOI)-, but not lysergic acid diethylamide (LSD)-elicited head bobs in rabbit
      medial prefrontal cortex.
AB  - The phenethylamine and indoleamine classes of hallucinogens demonstrate distinct
      pharmacological properties, although they share a serotonin(2A) (5-HT(2A))
      receptor mechanism of action (MOA). The 5-HT(2A) receptor signals through
      phosphatidylinositol (PI) hydrolysis, which is initiated upon activation of
      phospholipase C (PLC). The role of PI hydrolysis in the effects of hallucinogens
      remains unclear. In order to better understand the role of PI hydrolysis in the
      MOA of hallucinogens, the PLC inhibitor, 1-[6-((17beta-3-methoxyestra-1,3,5(10)
      trien-17-yl)amino)hexyl]-1H-pyrrole-2,5-dione (U73122), was used to study the
      effects of two hallucinogens, the phenethylamine, (+/-)-1-(2,5-dimethoxy-4
      iodophenyl)-2-aminopropane (DOI), and the indoleamine, lysergic acid diethylamide
      (LSD). PI hydrolysis was quantified through release of [3H]inositol-4-phosphate
      from living rabbit frontocortical tissue prisms. Head bobs were counted after
      hallucinogens were infused into the medial prefrontal cortex (mPFC) of rabbits.
      Both DOI and LSD stimulated PI hydrolysis in frontocortical tissue through
      activation of PLC. DOI-stimulated PI hydrolysis was blocked by 5-HT(2A/2C)
      receptor antagonist, ketanserin, whereas the LSD signal was blocked by 5
      HT(2B/2C) receptor antagonist, SB206553. When infused into the mPFC, both DOI-
      and LSD-elicited head bobs. Pretreatment with U73122 blocked DOI-, but not LSD
      elicited head bobs. The two hallucinogens investigated were distinct in their
      activation of the PI hydrolysis signaling pathway. The serotonergic receptors
      involved with DOI and LSD signals in frontocortical tissue were different.
      Furthermore, PLC activation in mPFC was necessary for DOI-elicited head bobs,
      whereas LSD-elicited head bobs were independent of this pathway. These novel
      findings urge closer investigation into the intracellular mechanism of action of
      these unique compounds.

PMID- 23123703
TI  - Brain-derived neurotrophic factor and the course of experimental cerebral
      malaria.
AB  - The role of neurotrophic factors on the integrity of the central nervous system
      (CNS) during cerebral malaria (CM) infection remains obscure, but the long
      standing neurocognitive sequelae often observed in rescued children can be
      attributed in part to the modulation of neuronal survival and synaptic
      plasticity. To discriminate the contribution of key responses in the time
      sequence of the pathogenic events that trigger the development of neurocognitive
      malaria syndrome we defined four stages (I-IV) of the neurological progression of
      CM in C57BL/6 mice infected with Plasmodium berghei ANKA. Upregulation of ICAM-1,
      VCAM-1, e-selectin and p-selectin expression was detected in all cerebral regions
      before parasitized red blood cells (pRBC) accumulation. As the severity of
      symptoms increased, BDNF mRNA progressively diminished in several brain regions,
      earliest in the thalamus-hypothalamus, cerebellum, brainstem and cortex, and
      correlated with a four-stage disease sequence. Immunohistochemical confocal
      microscopy revealed changes in the BDNF distribution pattern, suggesting altered
      axonal transport. During CM progression, molecular markers of neurological
      infection and inflammation in the parasite and the host, respectively, were
      accompanied by a switch in the brain constitutive proteasome to the
      immunoproteasome, which could impede normal protein turnover. In parallel with
      BDNF downregulation, NCAM expression also diminished with increased CM severity.
      Together, these data suggest that changes in BDNF availability could be involved
      in the pathogenesis of CM.

PMID- 23123704
TI  - Induction of the perceptual correlate of human long-term potentiation (LTP) is
      associated with the 5-HTT genotype.
AB  - The purpose of the present study was to examine how genetic variability in the
      promoter of the SLC6A4 gene encoding the serotonin transporter (5-HTT) may
      influence induction of long-term potentiation (LTP). The genotyping of the 53
      healthy volunteers was performed by a combination of TaqMan assay and gel
      electrophoresis. Based on the transcription rates, the subjects were divided in 3
      groups; 5-HTT SS, 5-HTT SL(G)/L(A)L(G)/SL(A) and 5-HTT L(A)L(A). The intensity of
      pain to test stimuli was rated on a visual analog scale (VAS). High frequency
      stimulation (HFS) conditioning applied to one arm was used to induce LTP. Only a
      minor change in pain was observed following the HFS conditioning evoked by
      electrical test stimuli delivered through the conditioning electrode. Moreover,
      the change in pain evoked by test stimuli delivered through the conditioning
      electrode was not related to the 5-HTT genotype. However, we observed a clear
      increase in pain following the HFS conditioning evoked by mechanical pin-prick
      test stimuli delivered at the skin adjacent to the conditioning. Also, the 9
      individuals with the 5-HTT SS genotype reported more pain than individuals with 5
      HTT SL(G)/L(A)L(G)/SL(A) genotype following HFS conditioning on mechanical pin
      prick test stimuli. Thus, the present data show that induction of the perceptual
      correlate of human LTP is associated with the genetic variability in the gene
      encoding the 5-HTT. Taken together, this suggests that the expression of 5-HTT,
      may be important for induction of LTP in humans.

PMID- 23123705
TI  - Involuntary attentional capture by speech and non-speech deviations: a combined
      behavioral-event-related potential study.
AB  - This study applied an auditory distraction paradigm to investigate involuntary
      attention effects of unexpected deviations in speech and non-speech sounds on
      behavior (increase in response time and error rate) and event-related brain
      potentials (DeltaN1/MMN and P3a). Our aim was to systematically compare identical
      speech sounds with physical vs. linguistic deviations and identical deviations
      (pitch) with speech vs. non-speech sounds in the same set of healthy volunteers.
      Sine tones and bi-syllabic pseudo-words were presented in a 2-alternative forced
      choice paradigm with occasional phoneme deviants in pseudo-words, pitch deviants
      in pseudo-words, or pitch deviants in tones. Deviance-related ERP components were
      elicited in all conditions. Deviance-related negativities (DeltaN1/MMN) differed
      in scalp distribution between phoneme and pitch deviants within phonemes,
      indicating that auditory deviance-detection partly operates in a deviance
      specific manner. P3a as an indicator of attentional orienting was similar in all
      conditions, and was accompanied by behavioral indicators of distraction. Yet
      smaller behavioral effects and prolonged relative MMN-P3a latency were observed
      for pitch deviants within phonemes relative to the other two conditions. This
      suggests that the similarity and separability of task-relevant and task
      irrelevant information is essential for the extent of attentional capture and
      distraction.

PMID- 23123707
TI  - Alexithymia is related to differences in gray matter volume: a voxel-based
      morphometry study.
AB  - OBJECTIVE: Alexithymia has been characterized as the inability to identify and
      describe feelings. Functional imaging studies have revealed that alexithymia is
      linked to reactivity changes in emotion- and face-processing-relevant brain
      areas. In this respect, anterior cingulate cortex (ACC), amygdala, anterior
      insula and fusiform gyrus (FFG) have been consistently reported. However, it
      remains to be clarified whether alexithymia is also associated with structural
      differences. METHODS: Voxel-based morphometry on T1-weighted magnetic resonance
      images was used to investigate gray matter volume in 17 high alexithymics (HA)
      and 17 gender-matched low alexithymics (LA), which were selected from a sample of
      161 healthy volunteers on basis of the 20-item Toronto Alexithymia Scale. Data
      were analyzed as statistic parametric maps for the comparisons LA>HA and HA>LA in
      a priori determined regions of interests (ROIs), i.e., ACC, amygdala, anterior
      insula and FFG. Moreover, an exploratory whole brain analysis was accomplished.
      RESULTS: For the contrast LA>HA, significant clusters were detected in the ACC,
      left amygdala and left anterior insula. Additionally, the whole brain analysis
      revealed volume differences in the left middle temporal gyrus. No significant
      differences were found for the comparison HA>LA. CONCLUSION: Our findings suggest
      that high compared to low alexithymics show less gray matter volume in several
      emotion-relevant brain areas. These structural differences might contribute to
      the functional alterations found in previous imaging studies in alexithymia.

PMID- 23123708
TI  - [Development of pharmaceutical research for cosmetic science and dermatology].

PMID- 23123706
TI  - Exogenous hydrogen sulfide protects against global cerebral ischemia/reperfusion
      injury via its anti-oxidative, anti-inflammatory and anti-apoptotic effects in
      rats.
AB  - The present study was undertaken to study the effects of exogenous hydrogen
      sulfide (H(2)S) on global cerebral ischemia-reperfusion(I/R) and the underlying
      mechanisms. After a 24h I/R, administration of NaHS, an exogenous donor for
      H(2)S, at the dose of 0.2 or 0.4 MUmol/kg significantly decreased the apoplexy
      index, neurological symptom scoring, and brain infarcted area as compared to the
      I/R group in a dose dependent manner. At the same time, NaHS-treated rats
      displayed significant reduction of MDA content, and striking increase of SOD
      activity in the brain tissues compared with I/R group. The up-regulated mRNA
      levels of p47(phox) and gp91(phox) subunits of NADPH oxidase were also suppressed
      by NaHS treatment. In this study, the pro-inflammatory markers TNF-alpha and MCP
      1 in I/R group were markedly increased by 24h I/R, which were significantly
      attenuated by NaHS in a dose-dependent manner. In contrast, the anti-inflammatory
      factor IL-10 was markedly induced by NaHS administration. In addition, the
      expression of the anti-apoptotic protein Bcl-2 was significantly decreased in I/R
      group compared with the sham-operated group. This reduction was significantly
      blunted in NaHS-treated group. On the contrary, the pro-apoptotic protein Bax
      content in brain tissues of I/R group was markedly elevated compared with sham
      operated animals. And such an induction of Bax content was significantly
      ameliorated by NaHS. Taken together, our results suggest that hydrogen sulfide
      has potent protective effect against a severe cerebral injury induced by a global
      I/R possibly through the inhibition of oxidative stress, inflammation and
      apoptosis.

PMID- 23123709
TI  - [Regulatory mechanisms of calcitonin gene-related peptide (CGRP) in skin
      inflammation].
AB  - Skin inflammation is one of several allergic symptoms that are regulated by
      several mediator molecules. One of these molecules, calcitonin gene-related
      peptide (CGRP) affects several immune cells including T cells, B cells,
      dendiritic cells and mast cells. CGRP binds to CGRP receptors composed of
      receptor activity-modifying protein 1 (RAMP1) and calcitonin receptor-like
      receptor (CLR) to modulate various functions such as pain transmission and
      vasodilation. Studies showing that CGRP physiologically regulates skin
      inflammation using a CGRP antagonist, capsaicin-induced depletion model, RAMP1
      deficient mice and mouse contact hypersensitivity (CHS) model have been reported.
      Interestingly, while CGRP has inhibitory effects on Th1-mediated CHS, it was
      demonstrated that CGRP enhances Th2-mediated CHS response. Moreover, these skin
      inflammations were affected by elevated CGRP concentrations through an abnormal
      condition of the nervous system induced by exposure to psychological stress or
      neonatal chemical stimulation. In this review, we present the importance of CGRP
      in the regulation of skin inflammation under the several nervous conditions and
      provide a new insight into understanding various types of skin inflammation and
      skin diseases.

PMID- 23123710
TI  - [Functions of prostaglandin receptors in contact dermatitis and application to
      drug discovery].
AB  - Contact dermatitis is an inflammatory skin disease caused by toxic factors that
      activate the skin innate immunity (irritant contact dermatitis) or by a T cell
      mediated hypersensitivity reaction (allergic contact dermatitis). These
      inflammatory skin diseases are sometimes still not easy to control. Therefore,
      the development of new effective drugs with fewer side effects is anticipated. In
      the skin under pathophysiological conditions, multiple prostaglandins are
      produced and their receptors are expressed in time- and/or cell-dependent
      manners. However, the precise role of prostaglandins and their receptors in
      contact dermatitis has not been fully understood. Recently, studies using mice
      with a disruption of each prostaglandin receptor gene, as well as receptor
      selective compounds revealed that prostaglandin receptors have manifold
      functions, sometimes resulting in opposite outcomes. Here, we review new advances
      in the roles of prostaglandin receptors in contact hypersensitivity as a
      cutaneous immune response model, and also discuss the clinical potentials of
      receptor-selective drugs.

PMID- 23123711
TI  - [Surfactant-induced itching and the involvement of histamine released from
      keratinocytes].
AB  - The primary function of surfactants is to remove dirt, exfoliated corneum cells,
      and microorganisms from the skin. However, the use of toiletries such as soaps
      and shampoos containing surfactants may cause adverse effects such as cutaneous
      irritation, dryness, and itching. Recently, skin pathologies, including dry skin,
      rough skin, and sensitive skin, have increased because of changes in living
      conditions and lifestyle. Although many people with skin pathologies complain of
      itching during and/or after skin washing using detergents, the mechanisms of
      detergent-induced itch are yet to be elucidated. Therefore, in this study, we
      investigated the mechanisms underlying surfactant-induced itching. We found that
      topical application of an anionic surfactant sodium laurate at an alkaline pH,
      but not N-lauroylsarcosine sodium salt at neutral pH, to mouse skin induced
      scratching, an itch-related response. Additionally, we found that the sodium
      laurate-induced scratching was inhibited by H(1) histamine receptor antagonist,
      but not mast cell deficiency. Sodium laurate application increased histamine
      content and the level of the active form (53 kDa) of L-histidine decarboxylase
      (HDC) in the mouse epidermis, but not the dermis. Furthermore, addition of sodium
      laurate to a human epidermal cell culture increased histamine release and HDC
      levels, without affecting cell viability. These results suggest that surfactants
      with alkaline properties are pruritogenic and that the pruritus is induced by the
      histamine released from epidermal keratinocytes. The increase in histamine
      release may be attributable to the activation of HDC in epidermal keratinocytes.

PMID- 23123712
TI  - [Safety assessment of nanomaterials for development of nano-cosmetics].
AB  - A diverse array of nanomaterials (NMs), such as amorphous nanosilica (nSP),
      carbon nanotubes and titanium dioxide, has become widespread in use due to the
      development of nanotechnology. NMs are already being applied in universal fields
      because they have unique physicochemical properties. On the other hands, the
      safety of NMs has not been well assessed, because NMs have been considered as
      safe as common larger sized materials which are known not to be absorbed by the
      body. Because NMs have the potential to improve the quality of human life, it is
      essential to ensure the safety of NMs and provide information for designing safer
      NMs. In this regard, we studied the biological distribution and hazard
      identification of nSP following dermal administration, because nSP is used NMs in
      the cosmetics field. In the future, our study would help to set the no observed
      adverse effect level (NOAEL) and acceptable daily intake (ADI), and be useful
      information for the safety/hazard assessment and evaluation.

PMID- 23123713
TI  - [Evaluation of efficacy and safety of drugs absorbed through skin using their
      physicochemical parameters].
AB  - Skin has been paid attention as a site of application of prescription drugs, over
      the-counter drugs (non-prescription drugs) and cosmetics. Skin permeation and
      skin concentration of the compounds should be considered after topical
      administration, as well as their blood concentration to evaluate efficacy and
      safety. Since the evaluation of the amount of drugs permeated through skin is
      important for topically applied drugs, studies on the skin permeation has been
      greatly advanced. In addition, many reports proved that skin permeabilities of
      drugs could be predicted from physicochemical parameters of drugs. On the other
      hand, few reports have been found on the prediction of skin concentration of
      drugs. Furthermore, many experimented problems are left to determine the skin
      concentration of drugs: severe consume of human or animal skins, difficult
      removal of applied drugs from the skin surface, low drug extraction ratio from
      skin and low sensitivity to determine skin concentration of drugs, and
      requirement of long time measurement. Thus, fast and accurate measurement of skin
      concentration of applied drugs are urgently required. This report describes the
      relationship between skin permeation and skin concentration, and the prediction
      of skin concentration of drugs using skin permeation parameters of drugs.

PMID- 23123714
TI  - [Possibility of therapy of brain functions by intranasal administration].

PMID- 23123715
TI  - [Characteristics of olfactory epithelium and manipulations of neural functions in
      the brain by the intranasal administration].
AB  - Olfactory cells receive numerous odorants including toxic substances. To avoid
      complete loss of the olfactory function by toxic odorants, continuous
      neurogenesis of olfactory cells occurs even at adulthood. Newly generated
      olfactory neurons extend their axons to the olfactory bulb. Various molecules
      including polypeptides, proteins, polynucleotides, virus, and cells administrated
      intranasally have been reported to move from the olfactory epithelium to the
      brain tissue via the olfactory epithelium-olfactory bulb pathway. I discuss the
      pathway of substances intranasally administrated to the brain from the view point
      of characteristics of the olfactory epithelium.

PMID- 23123717
TI  - [Clinical diagnosis of the olfactory nerve transport function].
AB  - Nasal administration of macromolecular drugs (peptides, nanoparticles) has a
      possibility to enable a drug delivery system beyond the blood brain barrier via
      olfactory nerve transport. Basic research on nasal drug delivery to the brain has
      been well studied. However, evaluation of the olfactory nerve transport function
      in patients with olfactory disorders has yet to be done, although such an
      evaluation is important in selecting candidates for clinical trials. Current
      olfactory function tests are useful for the analysis of olfactory thresholds in
      olfaction-impaired patients. However, the usefulness of using the increase in
      olfactory thresholds in patients as an index for evaluating olfactory nerve
      damage has not been confirmed because of the difficulty in directly evaluating
      the viability of the peripheral olfactory nerves. Nasally administered thallium
      201 migrates to the olfactory bulb, as has been shown in healthy volunteers.
      Furthermore, transection of olfactory nerve fibers in mice significantly
      decreases migration of nasally administered thallium-201 to the olfactory bulb.
      The migration of thallium-201 to the olfactory bulb is reduced in patients with
      impaired olfaction due to head trauma, upper respiratory tract infections, and
      chronic rhinosinusitis, relative to the values in healthy volunteers. Nasally
      administrating thallium-201 followed by single photon emission computed
      tomography, X-ray computed tomography and magnetic resonance imaging might be
      useful in choosing candidates for clinical trials of nasal drug delivery methods
      to the brain.

PMID- 23123716
TI  - [Basic studies on the nasal delivery of insulin].
AB  - Nasal absorption of insulin was discussed to develop a delivery system that
      targets the systemic circulation or central nervous system. Formation of insulin
      dimer and hexamer affects not only the diffusivity but also the membrane
      permeability of insulin via aqueous channels. The Renkin function was used to
      evaluate penetration pathways of hydrophilic compounds containing insulin through
      aqueous channels, and pore size and occupancy of the pathways were obtained as
      the membrane parameters on the basis of the function. Cationic polymers applied
      on the mucosal membranes as penetration enhancers increased the number of
      pathways for the hydrophilic compounds in the tight junctions, which suggested
      that these compounds could be sufficient as additives for the nasal delivery of
      insulin. However, excess interaction of the cationic enhancers with anionic
      insulin suppressed insulin permeation, and protection of insulin against
      degradation in the permeation process was required to improve the nasal
      absorption. PEGylation of insulin could be a possible way to improve the nasal
      delivery of insulin. In addition, combination of PEGylated insulin and modified
      cyclodextrin, which form pseudorotaxanes, can be applicable for further
      modification of pharmacokinetic and pharmacodynamic properties of insulin. Such
      well-designed complex systems may be required for specific delivery of insulin to
      the central nervous system.

PMID- 23123718
TI  - [Analysis of oncogenic signaling pathway induced by a myeloproliferative neoplasm
      associated Janus kinase 2 (JAK2) V617F mutant].
AB  - Janus kinase 2 (JAK2) is an essential non-receptor type tyrosine kinase for
      various cytokine signals. In 2005, a somatic JAK2 mutation (V617F) was found in
      the majority of myeloproliferative neoplasm (MPN) patients. It has been shown
      that the V617F mutation caused the constitutive activation of JAK2, exhibiting
      the cytokine-independent survival and proliferation of Ba/F3 cells. In addition,
      tumorigenesis was induced after a transplantation of Ba/F3 cells expressing JAK2
      V617F mutant in nude mice, suggesting that JAK2 V617F mutant behaves as a potent
      oncogene product. We found that JAK2 V617F mutant causes aberrant activation of a
      transcription factor c-Myc, which is critical for the JAK2 V617F mutant-caused
      oncogenic activities. In the screening of genes which expression was induced by
      JAK2 V617F mutant, we detected the significant induction of target genes of c-Myc
      such as Aurora kinase A (Aurka) and ornithine decarboxylase (ODC). Interestingly,
      JAK2 V617F mutant enhanced resistance to cisplatin (CDDP)-induced DNA damage and
      ectopic expression of Aurka in Ba/F3 cells exhibited similar resistance to CDDP.
      Conversely, knockdown and inhibition of Aurka in cells expressing JAK2 V617F
      mutant abolished the resistance to CDDP, suggesting that Aurka is most likely
      critical for resistance to DNA damage in cells transformed by JAK2 V617F mutant.
      In addition, we found that ODC inhibitor, DL-alpha-difluoromethylornithine (DFMO)
      prevented the proliferation of the JAK2 V617F mutant-induced transformed cells.
      Taking these observations together, c-Myc plays an essential role in JAK2 V617F
      mutant-induced hematopoietic disorder and would be a good target for the
      treatment of MPN.

PMID- 23123719
TI  - [Development of cell-selective gene transfection method using sugar-modified and
      ultrasound-responsive liposomes].
AB  - In the post-genome era, the analysis of disease-related genes has rapidly
      advanced, and the medical application of the information obtained from gene
      analysis is being put into practice. In particular, the development of a novel
      system to transfect the gene of interest selectively and efficiently into
      targeted cells is essential for the gene therapy of refractory diseases, in vivo
      functional analysis of genes, and establishment of animal models for diseases.
      However, a suitable carrier for selective gene delivery to targeted cells remains
      to be developed. The sonoporation method using microbubbles and ultrasound (US)
      exposure is one of the most promising approaches for effective gene transfection.
      However, it is difficult to transfect the therapeutic gene into the targeted
      organs/cells selectively by the conventional sonoporation method. Recently, our
      group has developed mannose-modified and US-responsive carriers/nucleic acid
      complexes (Man-PEG(2000) bubble lipoplexes), and succeeded in obtaining the
      enhanced and selective gene expression in mannose receptor-expressing cells by
      combination with US exposure. In this review, I described our gene transfection
      methods using Man-PEG(2000) bubble lipoplexes and external US exposure.
      Additionally, I also reviewed the enhancing mechanism of gene expression focusing
      on the intracellular transporting processes, in vivo distribution, and the
      activation of transcriptional factors. I believe that these findings help in the
      development of an effective gene transfection system using US-exposing system.

PMID- 23123720
TI  - [Platinum agent-induced nephrotoxicity via organic cation transport system].
AB  - Platinum agents are widely used in cancer chemotherapy. Cisplatin, carboplatin,
      oxaliplatin and nedaplatin have a common chemical structure consisting of
      platinum, carrier groups and leaving groups, and undergo the similar mechanism of
      cytotoxicity. Only cisplatin induces nephrotoxicity, although the molecular
      mechanism involved is unclear. Organic cation transporter (OCT)/SLC22A, and
      multidrug and toxin extrusion (MATE)/SLC47A play a role in renal handling of
      cationic drug in the kidney. We focused on a role of transporters in
      nephrotoxicity of platinum agents. OCT2 mediates the transport of cisplatin and
      is the determinant of cisplatin-induced nephrotoxicity. In addition, MATE1
      protects cisplatin-induced nephrotoxicity. Oxaliplatin, which was a superior
      substrate of the luminal efflux transporter, MATE2-K as well as OCT2, did not
      show nephrotoxicity. Moreover, carboplatin and nedaplatin were not transported by
      these transporters. Substrate specificity could regulate the features of platinum
      agents. Recent findings indicate that organic cation transporters are key to the
      nephrotoxicity of platinum agents.

PMID- 23123721
TI  - [Asymmetric synthesis of multi-substituted beta-lactams via C-N axially chiral
      enolates in intramolecular conjugate addition].
AB  - The synthesis of beta-lactams with contiguous tetra- and trisubstituted carbon
      centers has been accomplished via the 4-exo-trig intramolecular conjugate
      addition of C-N axially chiral enolates generated from alpha-amino acid
      derivatives. Use of a metal carbonate in a protic solvent (i.e., Cs(2)CO(3) in
      EtOH) was found to be critical for the success of the reaction. Under optimized
      reaction conditions, axially chiral enolates were generated in very low
      concentration, thereby favoring intramolecular conjugate addition while
      minimizing intermolecular side reactions. The highly strained beta-lactam
      enolates formed through this reversible intramolecular conjugate addition were
      rapidly protonated by EtOH in the reaction media to afford beta-lactams in up to
      97% ee.

PMID- 23123722
TI  - [Computational mutation analysis of enzymatic reaction].
AB  - Density functional theory (DFT) calculations are established as a useful research
      tool to investigate the structures and reactivity of biological systems; however,
      their high computational costs still restrict their applicability to systems of
      several tens up to a few hundred atoms. Recently, a combined quantum
      mechanical/molecular mechanical (QM/MM) approach has become an important method
      to study enzymatic reactions. In the past several years, we have investigated B12
      dependent diol dehydratase using QM/MM calculations. The enzyme catalyzes
      chemically difficult reactions by utilizing the high reactivity of free radicals.
      In this paper, we explain our QM/MM calculations for the structure and reactivity
      of diol dehydratase and report key findings with respect to the catalytic roles
      of the active-site amino acid residues, computational mutational analysis of the
      active-site amino acid residues, assignment of the central metal ion, and
      function of the central metal ion. Our QM/MM calculations can correctly describe
      the structures and activation barriers of intermediate and transition states in
      the protein environment. Moreover, predicted relative activities of mutants are
      consistent with experimentally observed reactivity. These results will encourage
      the application of QM/MM research to the mechanistic study of enzymatic
      reactions, functional analysis of active-site residues, and rational design of
      enzymes with new catalytic functions.

PMID- 23123723
TI  - [Improvement of dissolution test using micro-controlled roller pump].
AB  - The dissolution test is a core performance test in pharmaceutical development and
      quality control of solid drug products. The conventional HPLC dissolution method
      (batch-sampling method) involves many steps including the filtration, collection
      and replenishment of sample solutions. We previously reported a dissolution test
      that involved microdialysis methods (microdialysis-HPLC method) and allowed many
      steps to be omitted. However, the recovery rate of theophylline by the
      microdialysis-HPLC method was lower, and the decrease in the flow rate through
      the dialysis probe caused variation between each tablet. In this study, we have
      attempted to improve the dissolution test by using a precise micro-controlled
      roller pump and microfiltering probe (microfiltering-HPLC method). Sustained
      release preparations of Theodur (100 mg) were used, and the test solutions used
      were water, buffer at pH 1.2 and pH 6.8, and pH 6.8-buffer containing 0.1-1%
      polysorbate 80 or sodium lauryl sulfate. In all test solutions, the
      microfiltering-HPLC method was able to accomplish continuous sampling of sample
      solutions, and the recovery rate of theophylline was over 90%. The dissolution
      behavior by the microfiltering-HPLC method tends to reflect the pharmaceutical
      design in comparison with the batch-sampling method, and the standard deviations
      by the microfiltering-HPLC are lower than with the batch-sampling method. In
      addition, the microfiltering-HPLC method allows many steps to be omitted, such as
      the filtration, collection and replenishment of sample solutions. These findings
      provide significant information that can be used in the pharmaceutical
      development and quality assessment of solid drug products.

PMID- 23123724
TI  - [Effect of crystalline metastasis of lactose on hardness of compressed baby milk
      powder].
AB  - The purpose of this study was to examine the relationship between the crystalline
      metastasis of lactose, which is a main component baby milk powder, and the
      hardness of baby milk powder compressed by humidification followed by drying.
      Because baby milk powder is manufactured using a spray dryer, lactose in
      compressed baby milk powder exists in an amorphous (solid dispersion) form. X-ray
      diffraction measurement showed that this amorphous lactose metastasized to beta
      form crystalline lactose, and thereafter metastasized to the alpha-form during
      the humidification-drying process. As a result of this crystalline metastasis,
      the hardness of the compressed baby milk powder increased, and then decreased.
      Furthermore, scanning electron microscopy (SEM) showed bridging structures
      between the particles increased and then decreased during the humidification
      drying process. This showed that bridging structures between the particles
      produced by crystalline metastasis of lactose as a result of the humidification
      drying process, which leads to an increase in the hardness of the compressed baby
      milk powder. These results show that the necessary degree of hardness of the
      porous compressed baby milk powder (necessary for packaging and transportation)
      resulted from the humidification-drying process.

PMID- 23123725
TI  - Identification of polyoxometalates as inhibitors of basic fibroblast growth
      factor.
AB  - Angiogenesis is the process of new blood vessel formation from pre-existing ones.
      Angiogenic factors contribute to neovascularization that takes place in
      angiogenesis-dependent diseases, including cancer. Inhibiting the activity of the
      angiogenic factors to block the angiogenesis pathways is the current strategy of
      cancer therapy. Basic fibroblast growth factor (bFGF) is regarded as one of the
      most important angiogenic factors. Herein, we selected polyoxometalates (POMs)
      with different structures to study the interactions between bFGF and POMs. The
      results show that POMs could bind to the protein with high affinity, causing
      detectable changes in conformation and biophysical properties of protein. In
      addition, POMs could effectively inhibit the cell proliferation induced by bFGF.
      Significantly, we found that the structure, size and composition of POMs play a
      key role in the interactions between bFGF and POMs. This study will be meaningful
      for future screening and design of polyoxometalate-based anticancer drugs.

PMID- 23123726
TI  - Design, synthesis and biological evaluation of new peptide-based ureas and
      thioureas as potential antagonists of the thrombin receptor PAR1.
AB  - By applying a diversity oriented synthesis strategy for the search of new
      antagonists of the thrombin receptor PAR1, a series of peptide-based ureas and
      thioureas, including analogues of the PAR1 reference antagonist RWJ-58259, has
      been designed and synthesized. The general synthetic scheme involves reduction of
      basic amino acid-derived amino nitriles by hydrogen transfer from hydrazine
      monohydrate in the presence of Raney Ni, followed by reaction with diverse
      isocyanates and isothiocyanates, and protecting group removal. All new compounds
      have been evaluated as inhibitors of human platelet aggregation induced by the
      PAR1 agonist SFLLRN. Some protected peptide-based ureas displayed significant
      antagonist activity.

PMID- 23123727
TI  - Synthesis and antibacterial activity of novel 1,3-diphenyl-1H-pyrazoles
      functionalized with phenylalanine-derived rhodanines.
AB  - In the present study, a series of novel 1,3-diphenyl-1H-pyrazoles functionalized
      with phenylalanine-derived rhodanine derivatives were synthesized and evaluated
      for their antibacterial activity. Compounds 4, 6, 9, 10, 12 and 15 exhibited
      stronger activity than the standard drugs, norfloxacin and oxacillin, with MIC
      values of 1 MUg/mL against methicillin-resistant Staphylococcus aureus and
      quinolone-resistant S. aureus. None of the compounds showed any activity against
      Gram-negative bacteria.

PMID- 23123728
TI  - Synthesis, biological evaluation and molecular docking studies of 3-(triazolyl)
      coumarin derivatives: effect on inducible nitric oxide synthase.
AB  - A series of 3-(triazolyl)-coumarins were synthesized and tested as anti
      inflammatory agents. It was possible to infer that these compounds do not alter
      the interaction of LPS with TLR-4 or TLR-2, as the intracellular pathways
      involved in the TNF-alpha secretion and COX-2 activity were not affected.
      Nevertheless, the compounds inhibited iNOS-derived NO production, without
      affecting the eNOS activity. The outcome of the docking studies showed that
      pi...pi interactions with the heme group are important for the iNOS inhibition,
      thus making compound 3c a promising lead. Moreover, the efficacy of this compound
      was visualized by the reduced number of neutrophils in the LPS-inflamed
      subcutaneous tissue. Together, biological and docking data show that triazolyl
      substituted coumarins, that can act on iNOS, are a good scaffold to be explored.

PMID- 23123730
TI  - Association between MTHFR C677T polymorphism and primary open-angle glaucoma: a
      meta-analysis.
AB  - Epidemiological studies have evaluated the association between
      methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and primary open
      angle glaucoma (POAG) risk. However, the results remain conflicting. The aim of
      this study was to investigate the association between MTHFRC677T polymorphism and
      POAG risk. All genetic association studies on MTHFR C677T polymorphism and POAG
      were systematically searched by the electronic databases PubMed, Embase and Web
      of Science. Study selection, data abstraction and study quality evaluation were
      conducted in duplicate independently. The strength of association between MTHFR
      C677T polymorphism and POAG was measured by odds ratios (ORs) and 95% confidence
      intervals (CIs). Publication bias was tested by Begg's funnel plot and Egger's
      regression test. A total of 10 studies including 1224 cases and 1105 controls
      were included in our final meta-analysis. There was no evidence of significant
      association of the overall population (for allelic model: OR=1.17, 95% CI=0.94
      1.46; for additive model: OR=1.15, 95% CI=0.85-1.57; for dominant model: OR=1.19,
      95% CI=0.92-1.55 and for recessive model: OR=1.11, 95% CI=0.83-1.49). Significant
      associations were found between MTHFR C677T polymorphisms and POAG in allelic
      model (OR=1.39, 95% CI=1.05-1.83) and additive model (OR=1.88, 95% CI=1.04-3.43)
      for population-based (PB) subgroup. This meta-analysis suggested that there were
      significant associations between MTHFR C677T polymorphism and POAG in allelic
      model and additive model for PB subgroup which indicated that the T allele or TT
      genotype might increase the risk of POAG, whereas no evidence of significant
      association was shown of the overall studied population. However, this conclusion
      should be interpreted cautiously. More large sample-size and multi-ethnicity
      studies with well-defined POAG patients and well-study design are needed in the
      future study.

PMID- 23123729
TI  - ADAR1 ablation decreases bone mass by impairing osteoblast function in mice.
AB  - Bone mass is controlled through a delicate balance between osteoblast-mediated
      bone formation and osteoclast-mediated bone resorption. We show here that RNA
      editing enzyme adenosine deaminase acting on RNA 1 (ADAR1) is critical for proper
      control of bone mass. Postnatal conditional knockout of Adar1 (the gene encoding
      ADAR1) resulted in a severe osteopenic phenotype. Ablation of the Adar1 gene
      significantly suppressed osteoblast differentiation without affecting osteoclast
      differentiation in bone. In vitro deletion of the Adar1 gene decreased expression
      of osteoblast-specific osteocalcin and bone sialoprotein genes, alkaline
      phosphatase activity, and mineralization, suggesting a direct intrinsic role of
      ADAR1 in osteoblasts. ADAR1 regulates osteoblast differentiation by, at least in
      part, modulation of osterix expression, which is essential for bone formation.
      Further, ablation of the Adar1 gene decreased the proliferation and survival of
      bone marrow stromal cells and inhibited the differentiation of mesenchymal stem
      cells towards osteoblast lineage. Finally, shRNA knockdown of the Adar1 gene in
      MC-4 pre-osteoblasts reduced cyclin D1 and cyclin A1 expression and cell growth.
      Our results identify ADAR1 as a new key regulator of bone mass and suggest that
      ADAR1 functions in this process mainly through modulation of the intrinsic
      properties of osteoblasts (i.e., proliferation, survival and differentiation).

PMID- 23123731
TI  - MAP kinase signalling cascades and transcriptional regulation.
AB  - The MAP kinase (MAPK) signalling pathways play fundamental roles in a wide range
      of cellular processes and are often deregulated in disease states. One major mode
      of action for these pathways is in controlling gene expression, in particular
      through regulating transcription. In this review, we discuss recent significant
      advances in this area. In particular we focus on the mechanisms by which MAPKs
      are targeted to the nucleus and chromatin, and once there, how they impact on
      chromatin structure and subsequent gene regulation. We also discuss how systems
      biology approaches have contributed to our understanding of MAPK signaling
      networks, and also how the MAPK pathways intersect with other regulatory pathways
      in the nucleus. Finally, we summarise progress in studying the physiological
      functions of key MAPK transcriptional targets.

PMID- 23123732
TI  - A novel therapeutic system for malignant glioma: nanoformulation,
      pharmacokinetic, and anticancer properties of cell-nano-drug delivery.
AB  - Macrophage carriage, release, and antitumor activities of polymeric
      nanoformulated paclitaxel (PTX) were developed as a novel delivery system for
      malignant glioma. To achieve this goal, the authors synthesized PTX-loaded
      nanoformulations (nano-PTX), then investigated their uptake, release, and
      toxicological properties. Chemosensitivity was significant in U87 cells (P <
      0.05) at concentrations from 10(-4) to 10(-8) M following 72 hours' exposure to
      bone-marrow-derived macrophages (BMM)-nano-PTX in comparison with treatment with
      nano-PTX alone. The most significant reductions in U87 cell viability (P < 0.05)
      were observed in the transwell cocultures containing BMM-nano-PTX. Limited
      toxicity to BMM was observed at the same concentrations. BMM functions were
      tested by analysis of microtubules and actin filaments, as the cytoarchitecture,
      demonstrating a similar cytoskeleton pattern before and after nano-PTX was loaded
      into cells. This data indicate that nanoformulations of PTX facilitate cell
      uptake, delay toxicity, and show improved therapeutic efficacy by BMM-nano-PTX
      delivery. FROM THE CLINICAL EDITOR: In this study the delivery, release, and
      antitumor activity of polymeric nanoformulated paclitaxel carried by macrophages
      are described as a novel and efficient system for treatment of resistant
      malignant glioma.

PMID- 23123733
TI  - Phylogeny of Crocus (Iridaceae) based on one chloroplast and two nuclear loci:
      ancient hybridization and chromosome number evolution.
AB  - Crocus consists of about 100 species distributed from western Europe and northern
      Africa to western China, with the center of diversity on the Balkan Peninsula and
      in Asia Minor. Our study focuses on clarifying phylogenetic relationships and
      chromosome number evolution within the genus using sequences of the chloroplast
      trnL-F region, the nuclear ribosomal DNA internal transcribed spacer (ITS)
      region, and a part of the nuclear single-copy gene pCOSAt103. In a combined
      dataset of ITS and trnL-F sequences, 115 individuals representing 110 taxa from
      both subgenera and all sections and series of Crocus were analyzed with Bayesian
      phylogenetic inference. For pCOSAt103 79 individuals representing 74 Crocus taxa
      were included, and for the majority of them PCR amplicons were cloned and up to
      eight clones per individual were sequenced to detect allopolyploidization events.
      Romulea species were included as outgroup in both analyses. Characteristics of
      seed surface structures were evaluated by scanning electron microscopy.
      Phylogenetic analysis of ITS/trnL-F data resulted in a monophyletic genus Crocus,
      probably monophyletic sections Crocus and Nudiscapus, and inferred monophyly for
      eight of the 15 series of the genus. The C. biflorus aggregate, thought to be
      consisting of closely related subspecies, was found to be polyphyletic, the taxa
      occurring within three major clades in the phylogenetic tree. Cloning of
      pCOSAt103 resulted in the detection of homoeologous copies in about one third of
      the taxa of section Nudiscapus, indicating an allotetraploid origin of this
      section. Reconstruction of chromosome number evolution along the phylogenetic
      tree using a probabilistic and a parsimony approach arrived at partly
      contradictory results. Both analyses agreed however on the occurrence of multiple
      polyploidization and dysploidy events. B chromosomes evolved at least five times
      independently within the genus, preferentially in clades characterized by
      karyotype changes.

PMID- 23123735
TI  - A brief history of adrenal research: steroidogenesis - the soul of the adrenal.
AB  - The adrenal is a small gland that escaped anatomic notice until the 16th century,
      and whose essential role in physiology was not established until the mid 19th
      century. Early studies were confounded by failure to distinguish the effects of
      the cortex from those of the medulla, but advances in steroid chemistry permitted
      the isolation, characterization and synthesis of many steroids by the mid 20th
      century. Knowledge of steroid structures, radiolabeled steroid conversions, and
      the identification of accumulated urinary steroids in diseases of steroidogenesis
      permitted a generally correct description of the steroidogenic pathways, but one
      confounded by the failure to distinguish species-specific differences. The advent
      of cloning technologies and molecular genetics rapidly corrected and clarified
      the understanding of steroidogenic processes. Our laboratory in San Francisco was
      one of several contributing to this effort, focusing on human steroidogenic
      enzymes, the genetic disorders in their biosynthesis and the transcriptional and
      post-translational mechanisms regulating enzyme activity.

PMID- 23123734
TI  - Estrogen-related receptor alpha in normal adrenal cortex and adrenocortical
      tumors: involvement in development and oncogenesis.
AB  - AIMS: The nuclear hormone receptor estrogen-related receptor alpha (ERRalpha)
      regulates the activation of mitochondrial genes in various human tissues, but its
      role in the adrenal gland and its disorders has not been defined. Therefore, we
      examined ERRalpha expression in both normal adrenal cortex (NAC) and
      adrenocortical tumor (ACT) in order to study the possible correlation of ERRalpha
      with adrenal development and tumor development. METHODS: Human adrenal specimens
      (non-pathological fetal n=7; non-pathological post-birth n=40; aldosterone
      producing adenoma (APA) n=11; cortisol producing adenoma (CPA) n=11;
      adrenocortical carcinoma (ACC) n=8) were immunohistochemically examined in this
      study. NAC (n=13) and ACT (n=28) frozen tissue specimens were also available for
      studying ERRalpha mRNA levels. KEY FINDINGS: In fetal NAC tissues, ERRalpha
      labeling index (LI) in fetal zone (FZ) was significantly higher that that in
      neocortex (NC), and the differences among age groups for overall mean LI was
      statistically significant when analyzed according to individual cortical layers.
      ERRalpha LI was also significantly higher in ACC than in other types of ACT.
      ERRalpha mRNA was detected in NAC and all types of ACT. SIGNIFICANCE: Results of
      our present study suggest a possible role of ERRalpha in adrenal development and
      ACC.

PMID- 23123736
TI  - Damaged spermatogenic cells induce inflammatory gene expression in mouse Sertoli
      cells through the activation of Toll-like receptors 2 and 4.
AB  - Testicular inflammation, including noninfectious inflammatory responses in the
      testis, may impair male fertility. Mechanisms underlying the initiation of
      noninfectious testicular inflammation are poorly understood. In the current
      study, we demonstrate that damaged spermatogenic cell products (DSCPs) induce
      expression of various inflammatory mediators, including TNF-alpha, IL-1beta, IL
      6, and macrophage chemotactic protein 1 (MCP-1), in Sertoli cells. Notably, the
      DSCP-induced inflammatory gene expression was significantly reduced by knockout
      Toll-like receptor (TLR)2 or TLR4, and abolished by double knockout TLR2 and TLR4
      (TLR2(-/-)TLR4(-/-)). MCP-1 secreted by Sertoli cells after stimulation with
      DSCPs promotes macrophage migration. We also provide evidence that busulfan
      induced spermatogenic cell damages in vivo upregulate TNF-alpha and MCP-1
      expression in Sertoli cells, and facilitate macrophage infiltration into the
      testis in wild-type mice. These phenomena were not observed in TLR2(-/-)TLR4(-/-)
      mice. Data indicate that DSCPs induce inflammatory gene expression in Sertoli
      cells via the activation of TLR2 and TLR4, which may initiate noninfectious
      inflammatory responses in the testis. The results provide novel insights into the
      mechanisms underlying damaged spermatogenic cell-induced testicular inflammation.

PMID- 23123737
TI  - Involvement of the ANGPTs/Tie-2 system in ovarian hyperstimulation syndrome
      (OHSS).
AB  - Ovarian hyperstimulation syndrome (OHSS) is a disorder associated with ovarian
      stimulation. OHSS features are ovarian enlargement with fluid shifting to the
      third space. Disturbances in the vasculature are considered the main changes that
      lead to OHSS. Our aim was to analyze the levels of angiopoietins 1 and 2 (ANGPT1
      and 2) and their soluble and membrane receptors (s/mTie-2) in follicular fluid
      (FF) and in granulosa-lutein cells culture (GLCs) from women at risk of
      developing OHSS. We also evaluated the effect of ANGPT1 on endothelial cell
      migration. In ovaries from an OHSS rat model, we analyzed the protein
      concentration of ANGPTs, their mTie-2 receptor, and platelet-derived growth
      factor PDGF-B, -D and PDGFR-beta. ANGPT1 levels were increased in both FF and
      GLCs from women at risk of OHSS. Incubation of these FF with an ANGPT1
      neutralizing antibody decreased endothelial cell migration. In the ovaries of
      OHSS rat model, mTie-2 protein levels increased and PDGF-B and -D decreased. In
      summary, these results suggest that ANGPT1 could be another mediator in the
      development of OHSS.

PMID- 23123739
TI  - Cytotoxic steroidal saponins from Ophiopogon japonicus.
AB  - Four new steroidal saponins, named ophiopogonin P-S (1-4), together with eleven
      known ones (5-15) were isolated from the tuberous roots of Ophiopogon japonicus.
      Their structures were elucidated by spectroscopic and chemical analysis.
      Compounds 2-15 were evaluated for their cytotoxic activity against five human
      tumor cell lines (HepG2, HLE, BEL7402, BEL7403 and Hela). Compounds 2, 5, 6, 8
      and 9 were cytotoxic for all cell lines tested. Compounds 7, 11 and 15 showed
      selective cytotoxicity against some of the cell lines. The structure-activity
      relationship of these compounds was discussed.

PMID- 23123738
TI  - DHEA metabolites activate estrogen receptors alpha and beta.
AB  - Dehydroepiandrosterone (DHEA) levels were reported to associate with increased
      breast cancer risk in postmenopausal women, but some carcinogen-induced rat
      mammary tumor studies question this claim. The purpose of this study was to
      determine how DHEA and its metabolites affect estrogen receptors alpha or beta
      (ERalpha or ERbeta)-regulated gene transcription and cell proliferation. In
      transiently transfected HEK-293 cells, androstenediol, DHEA, and DHEA-S activated
      ERalpha. In ERbeta transfected HepG2 cells, androstenedione, DHEA,
      androstenediol, and 7-oxo DHEA stimulated reporter activity. ER antagonists ICI
      182,780 (fulvestrant) and 4-hydroxytamoxifen, general P450 inhibitor miconazole,
      and aromatase inhibitor exemestane inhibited activation by DHEA or metabolites in
      transfected cells. ERbeta-selective antagonist R,R-THC (R,R-cis-diethyl
      tetrahydrochrysene) inhibited DHEA and DHEA metabolite transcriptional activity
      in ERbeta-transfected cells. Expression of endogenous estrogen-regulated genes:
      pS2, progesterone receptor, cathepsin D1, and nuclear respiratory factor-1 was
      increased by DHEA and its metabolites in an ER-subtype, gene, and cell-specific
      manner. DHEA metabolites, but not DHEA, competed with 17beta-estradiol for
      ERalpha and ERbeta binding and stimulated MCF-7 cell proliferation, demonstrating
      that DHEA metabolites interact directly with ERalpha and ERbetain vitro,
      modulating estrogen target genes in vivo.

PMID- 23123740
TI  - 3beta,5alpha,6beta-Oxygenated sterols from the South China Sea gorgonian
      Muriceopsis flavida and their tumor cell growth inhibitory activity and apoptosis
      inducing function.
AB  - Three new polyhydroxysterols, named muriflasteroids A-C (1-3) were isolated from
      the South China Sea gorgonian Muriceopsis flavida, together with sixteen known
      analogs, cholest-3beta,5alpha,6beta-triol,3beta-acetate (4), 5alpha
      methoxycholest-3beta,6beta-diol (5), (22E)-cholest-22-en-3beta,5alpha,6beta-triol
      (6), cholest-3beta,5alpha,6beta-triol (7), (22E)-24-norcholest-22-en
      3beta,5alpha,6beta-triol (8), (22E,24S)-ergost-22-en-3beta,5alpha,6beta-triol
      (9), ergost-24(28)-en-3beta,5alpha,6beta-triol (10), (22E)-cholest-7,22-dien
      3beta,5alpha,6beta-triol (11), cholest-7-en-3beta,5alpha,6beta-triol (12), (22E)
      24-norcholest-7,22-dien-3beta,5alpha,6beta-triol (13), ergost-7,24(28)-dien
      3beta,5alpha,6beta-triol (14), (22E,24R)-ergost-7,22-dien-3beta,5alpha,6beta
      triol (15), (22E)-cholest-22-en-1beta,3beta,5alpha,6beta-tetrol (16), (22E)-24
      norcholest-22-en-1beta,3beta,5alpha,6beta-tetrol (17), cholest
      1beta,3beta,5alpha,6beta-tetrol (18), and (24xi)-ergost-1beta,3beta,5alpha,6beta
      tetrol (19). The structures of the new compounds were elucidated by detailed
      spectroscopic analysis in combination with comparison of reported data. All the
      compounds are reported for the first time from the animal. In the bioassay in
      vitro, these compounds exhibited different levels of growth inhibition activity
      against A549 and MG63 cell lines. In particular, compound 18 displayed a
      considerable activity, being similar as that of positive control adriamycin. An
      annexin V analysis indicated that compounds 7 and 18 can significantly induce
      apoptosis in A549 cell, and compound 7 is more potent in the induction of
      apoptosis. Preliminary structure-activity analysis suggests that the acetylation
      on 3-OH and appearance of Delta7 may decrease the activity while substitution of
      1-OH and the nature of side chain may also play an important role in the
      activity. Methylation of 5-OH contributed a little to the activity.

PMID- 23123741
TI  - Testosterone-induced persistent susceptibility to Plasmodium chabaudi malaria:
      long-term changes of lincRNA and mRNA expression in the spleen.
AB  - Testosterone (T) is known to induce persistent susceptibility to blood-stage
      malaria of Plasmodium chabaudi in otherwise resistant female C57BL/6 mice, which
      is associated with permanent changes in mRNA expression of the liver. Here, we
      investigate the spleen as the major effector against blood-stage malaria for any
      possible T-induced long-term effects on lincRNA and mRNA expression. Female
      C57BL/6 mice were treated with T for 3 weeks, then T was withdrawn for 12 weeks
      before challenging with P. chabaudi. LincRNA and mRNA expression was examined
      after 12 weeks of T-withdrawal and after subsequent infections using Agilent
      whole mouse genome oligo microarrays. Our data show for the first time long-term
      effects of T on lincRNA expression evidenced directly as persistent changes after
      T-withdrawal for 12 weeks and indirectly as altered responsiveness of expression
      to P. chabaudi infections. There are 3 lincRNA-species upregulated and 10
      lincRNAs downregulated by more than 2-fold (p<0.01). In addition, 11 and 10 mRNAs
      are persistently up- and downregulated by T, respectively. These changes remain
      not sustained during infections at peak parasitemia, when 15 other lincRNAs and 9
      other mRNAs exhibit an altered expression. The only exception is the Tnk1-mRNA
      encoding the non-receptor tyrosine kinase 1 that is persistently downregulated by
      0.34-fold after T-withdrawal and that becomes upregulated by 5.9-fold upon
      infection at peak parasitemia, suggesting an involvement of tyrosine
      phosphorylation by Tnk1 in mediating long-term effects of T in the spleen. The T
      induced changes in splenic mRNA expression are totally different to those
      previously observed in the liver. Collectively, our data support the view that T
      induces long-term organ-specific changes in both lincRNA and mRNA expression,
      that presumably contribute to organ-specific dysfunctions upon infection with
      blood-stage malaria of P. chabaudi.

PMID- 23123742
TI  - Salivary testosterone in female-to-male transgender adolescents during treatment
      with intra-muscular injectable testosterone esters.
AB  - INTRODUCTION: In our hospital, female-to-male (FtM) transgender adolescents from
      the age of 16 are treated with two- or four-weekly intra-muscular injections of
      testosterone-esters. Some patients treated with four-weekly injections have
      complaints of fatigue and experience mood swings towards the end of the inter
      injection period, which calls for an evaluation of the time-course of
      testosterone levels between injections. Evaluation of salivary testosterone is a
      practical approach for sequential measurements. Since only ~2% of total serum
      testosterone is present in saliva, a sensitive assay is necessary. The objective
      was to develop an isotope dilution-liquid chromatography-tandem mass spectrometry
      method (ID-LC-MS/MS) for salivary testosterone measurements and to evaluate the
      testosterone profiles after testosterone-ester mixture injections in FtM
      adolescents. EXPERIMENTAL: FtM treated with 125 mg/2 weeks or with 250 mg/4 weeks
      depots of testosterone-ester mixture collected saliva at different time
      intervals. Salivary testosterone was measured by a thoroughly validated ID-LC
      MS/MS assay. RESULTS: An ID-LC-MS/MS method for measuring salivary testosterone
      was developed with adequate accuracy and specificity. The reference range was
      established at 135-400 pmol/L. Testosterone levels peaked supra-physiologically
      immediately post-injection, and decreased to levels within the male reference
      range after nine days in all patients. 250 mg/4 weeks depots resulted in values
      below the reference range at the end of the 4 weeks. DISCUSSION: The development
      of an adequate ID-LC-MS/MS method for measuring salivary testosterone allowed us
      to investigate the testosterone profile in FtM-adolescents after testosterone
      esters mixture injections. These injections lead to extreme concentrations which
      may affect the wellbeing of the patients.

PMID- 23123743
TI  - Estrogen receptor ESR1 regulates the phospholipase C-inositol phosphate signaling
      in the hippocampus from rats in proestrous and estrous phases.
AB  - The aim of the present study was to investigate the involvement of estrogen
      receptors in the activation of phospholipase C (PLC)-phosphoinositide hydrolysis
      in the hippocampus from rats in estrous and proestrous phases. 17beta-Estradiol
      (E2) and ESR1-selective agonist PPT, but not ESR2-selective agonist DPN, induced
      a rapid increase on total [3H]-inositol phosphate accumulation in the hippocampus
      from both rats. These effects are mediated by PLC activation, since the
      inhibition of this protein decreased the total [3H]-inositol phosphate
      accumulation. The pretreatment with ESR1 and ESR2 antagonist ICI 182,780, but not
      with GPER antagonist G-15, blocked the total [3H]-inositol phosphate accumulation
      induced by E2 and PPT, confirming that ESR1 is upstream component regulating this
      rapid effect. SRC family of protein tyrosine kinases inhibitor PP2 blocked the
      total [3H]-inositol phosphate accumulation induced by E2 and PPT in hippocampus,
      suggesting that ESR1 undergoes translocation from the nuclei to the plasma
      membrane region via SRC to activate rapid signaling pathways. Furthermore, the
      magnitude of the response to E2 and PPT was higher in hippocampus from rats in
      proestrous than in estrous. On the other hand, the expression of the ESR1 is
      higher in hippocampus from rats in estrous than in proestrous, indicating that
      the regulation of this receptor by estrous cycle does not play a role in the
      magnitude of the response to E2 and PPT in hippocampus. In conclusion, our
      results indicate that E2 activates SRC-mediated translocation of ESR1 to the
      plasma membrane, which results in the activation of PLC-inositol phosphate
      signaling pathway in rat hippocampus. Thus, these rapid estrogen actions in
      hippocampus might be a key step mediating cellular events important for learning
      and memory.

PMID- 23123744
TI  - Do as I say, not as I do.
AB  - Nurses readily dispense prescriptions and advice but, what do they do themselves?
      Do they ever take their own medicine? The often heard saying, 'Do as I say, not
      as I do', could be an adage that is repeatedly used by nurses when working with
      and treating patients. Patients who are being treated by overweight nurses,
      nurses who are stressed and those who smoke may take with a pinch of salt
      (literally and metaphorically) any healthcare advice being offered by those
      nurses.

PMID- 23123745
TI  - In defence of the National Health Service.
AB  - As the Government takes the flack for the chaotic implementation of its re
      organisation of NHS structures, the real agenda behind it is starting to emerge.
      David Cameron's plans are designed to unpick the very fabric of a national health
      service and undermine its founding values.

PMID- 23123746
TI  - Hand hygiene compliance: is there  a theory-practice-ethics gap?
AB  - Practice is usually based on tradition, rituals and outdated information; there
      is often an additional gap between theoretical knowledge and its application in
      practice. This theory-practice gap has long existed (Allmark, 1995; Hewison et
      al, 1996). It often arises when theory is ignored because it is seen as
      idealistic and impractical, even if it is practical and beneficial. Most research
      relating to the lack of integration between theory and practice has concluded
      that environmental factors are responsible and will affect learning and practice
      outcomes. The author believes an additional dimension of ethics is required to
      bridge the gap between theory and practice. This would be a moral obligation to
      ensure theory and practice are integrated. To implement new practices
      effectively, healthcare practitioners must deem these practices worthwhile and
      relevant to their role. This introduces a new concept that the author calls the
      theory-practice-ethics gap. This theory-practice-ethics gap must be considered
      when examining some of the unacceptable outcomes in healthcare practice (Mortell,
      2009). The literature suggests that there is a crisis of ethics where theory and
      practice integrate, and practitioners are failing to fulfil their duty as
      providers of healthcare and as patient advocates. This article examines the
      theory-practice-ethics gap when applied to hand hygiene. Non-compliance exists in
      hand hygiene among practitioners, which may increase patient mortality and
      morbidity rates, and raise healthcare costs. Infection prevention and control
      programmes to improve hand hygiene among staff include: ongoing education and
      training; easy access to facilities such as wash basins; antiseptic/alcohol
      handgels that are convenient, effective, and skin- and user-friendly; and
      organisational recognition and support for clinicians in hand washing and handgel
      practices. Yet these all appear to have failed to achieve the required and
      desired compliance in hand hygiene.

PMID- 23123747
TI  - Exploring the cultural validity  of rheumatology outcomes.
AB  - In rheumatoid arthritis (RA), the use of a 'core' set of treatment outcomes was
      pioneered to ensure that the same outcomes are measured across all clinical
      trials to enable comparison of trial results. However, studies have not
      investigated the influence of patients' ethnic and cultural backgrounds on
      treatment outcomes. This pilot study identified 74 treatment outcomes from female
      Punjabi RA patients, including 21 new ones that were not identified in previous
      research with white British RA patients. The social impact of RA created
      significant additional burden for these Punjabi women, with 'less stigmatisation'
      and 'improved ability to carry out family duties' generated as important new
      outcomes. This study illustrates a need to address cultural validity in outcome
      elicitation and prioritisation, to ensure that interventions are evaluated using
      criteria that have meaning for people with that condition.

PMID- 23123748
TI  - First annual pioneers of care awards celebrates nurses.
AB  - The Pioneers of Care awards recognises nurses who have gone above and beyond the
      call of duty to affect patient care in a positive, efficient and empathetic way,
      and have helped to tackle problems in frontline care and improve the lives of
      patients by introducing new techniques or innovations.

PMID- 23123749
TI  - Exploring advanced nursing practice: past, present and future.
AB  - This article examines the nature of advanced nursing practice. It identifies
      confusion around the terms of advanced nurse practitioners (ANPs), nurse
      practitioners and specialist nurses, and identifies what advanced practice is.
      The history of how ANPs evolved is discussed from its haphazard development to a
      more organised approach. Current advanced practice is identified, along with NHS
      plans for nurse development. Law, ethics and professional accountability are
      examined in relation to the additional responsibility ANPs have. Finally, the
      author's role as an ANP is considered within the context of primary care and NHS
      reforms.

PMID- 23123750
TI  - Transition from child and adolescent to adult mental health services.
AB  - This article explores key issues in relation to adolescence and the transition
      from Child and Adolescent Mental Health Services (CAMHS) to Adult Mental Health
      Services (AMHS). A national review of services revealed some concern and
      dissatisfaction regarding existing service provision. Nurses are employed in both
      of these services and are well placed to play a significant role during
      transition. The challenges and opportunities for services are explored with
      reference to key policy documents. Several factors contribute to better outcomes,
      including collaboration between CAMHS and AMHS, the young person and the family,
      aligning services with the young person's development and maturity, and
      approaching transition in a flexible way. These factors are highlighted with the
      use of a case study and with reference to the nurses' role.

PMID- 23123751
TI  - A strategy to improve the health  of children and young people.
AB  - Professor Alan Glasper discusses how proposals by the Children and Young People's
      Health Outcomes Forum seek to improve the health of children and young people.

PMID- 23123752
TI  - Perspectives on shared decision making in health care.
AB  - The relationship between nurses, doctors and patients is not equal in terms of
      power. The nurse or doctor has a body of knowledge that the patient does not. The
      patient may be feeling ill and nervous, perhaps fearing a bad diagnosis. The
      nurse or doctor is nearly always the most powerful person in the care equation.
      The playing field in health is not a level one.

PMID- 23123753
TI  - Facing the final year and reflecting on the journey.
AB  - Emma Louise Botten, a student nurse at King's College Hospital, reflects on the
      first two years of training and considers what the future holds, in terms of the
      final year, and her fast-approaching career as a qualified nurse.

PMID- 23123754
TI  - Teaching and Learning: from staff nurse to nurse consultant. Part 7: teaching a
      skill.
AB  - I am always fascinated to watch people who are very competent at a particular
      task performing that skill. There is a confident ease that marks out a skilled
      performer but if you look deeper below the actual physical movements you can
      observe that the almost intuitive actions are guided by visual cues and sensory
      feedback. However, it is one thing to perform a skill but it is another to teach
      it.

PMID- 23123755
TI  - He who pays the fiddler  calls the tune!
AB  - September 2012 marks the beginning of yet another academic year and whether you
      are a new pre-registration student reading this column for the very first time, a
      continuing pre-registration student making the transition from first to second,
      or second to third year, a newly-qualified or established practising nurse, this
      is an important time.

PMID- 23123756
TI  - All change please!
AB  - The season is slowly changing from summer to autumn; happy memories of holidays
      and sunny days linger on, but it is certainly a time for change.

PMID- 23123757
TI  - Three-dimensional noninvasive ultrasound Joule heat tomography based on the
      acousto-electric effect using unipolar pulses: a simulation study.
AB  - Electrical properties of biological tissues are highly sensitive to their
      physiological and pathological status. Thus it is of importance to image
      electrical properties of biological tissues. However, spatial resolution of
      conventional electrical impedance tomography (EIT) is generally poor. Recently,
      hybrid imaging modalities combining electric conductivity contrast and ultrasonic
      resolution based on the acousto-electric effect has attracted considerable
      attention. In this study, we propose a novel three-dimensional (3D) noninvasive
      ultrasound Joule heat tomography (UJHT) approach based on the acousto-electric
      effect using unipolar ultrasound pulses. As the Joule heat density distribution
      is highly dependent on the conductivity distribution, an accurate and high
      resolution mapping of the Joule heat density distribution is expected to give
      important information that is closely related to the conductivity contrast. The
      advantages of the proposed ultrasound Joule heat tomography using unipolar pulses
      include its simple inverse solution, better performance than UJHT using common
      bipolar pulses and its independence of a priori knowledge of the conductivity
      distribution of the imaging object. Computer simulation results show that using
      the proposed method, it is feasible to perform a high spatial resolution Joule
      heat imaging in an inhomogeneous conductive media. Application of this technique
      on tumor scanning is also investigated by a series of computer simulations.

PMID- 23123760
TI  - Genetics and mathematics: FMR1 premutation female carriers.
AB  - Neuropsychological investigations of FMR1 premutation carriers without FXTAS
      present one domain resulting in contradictory findings, namely that of
      mathematical skills. One reason for this might be that standard clinical
      batteries used so far may be inadequate to uncover precise deficits within
      specific mathematical skills. In fact, these batteries do not clearly distinguish
      between specific mathematical abilities and are therefore likely to provide only
      a generic indication of a deficit. Mathematical skills in a group of females with
      FMR1 premutation were investigated through the use of an extensive, theoretically
      grounded battery of mathematical tasks, encompassing counting, number
      comprehension, numerical transcoding, calculation skills and arithmetic
      principles. Moreover, the mental representation of numbers was assessed by
      studying the Spatial Numerical Association of Response Codes (SNARC) effect and
      mental number line (MNL) bisection. The FMR1 premutation group (N=18) comprised
      29-50 years old women of normal intelligence, who were individually matched on
      age, sex and education to a group of healthy participants (N=18). Specific yet
      subtle weaknesses were detected on processes of basic number understanding such
      as dealing with analogue scales and certain aspects of number transcoding, in the
      presence of otherwise spared calculation abilities.

PMID- 23123761
TI  - Effects of temperature on the nitric oxide-dependent modulation of the Frank
      Starling mechanism: the fish heart as a case study.
AB  - The Frank-Starling law is a fundamental property of the vertebrate myocardium
      which allows, when the end-diastolic volume increases, that the consequent
      stretch of the myocardial fibers generates a more forceful contraction. It has
      been shown that in the eel (Anguilla anguilla) heart, nitric oxide (NO) exerts a
      direct myocardial relaxant effect, increasing the sensitivity of the Frank
      Starling response (Garofalo et al., 2009). With the use of isolated working heart
      preparations, this study investigated the relationship between NO modulation of
      Frank-Starling response and temperature challenges in the eel. The results showed
      that while, in long-term acclimated fish (spring animals perfused at 20  degrees
      C and winter animals perfused at 10  degrees C) the inhibition of NO production
      by L-N5 (1-iminoethyl)ornithine (L-NIO) significantly reduced the Frank-Starling
      response, under thermal shock conditions (spring animals perfused at 10 or 15 
      degrees C and winter animals perfused at 15 or 20  degrees C) L-NIO treatment
      resulted without effect. Western blotting analysis revealed a decrease of peNOS
      and pAkt expressions in samples subjected to thermal shock. Moreover, an increase
      in Hsp90 protein levels was observed under heat thermal stress. Together, these
      data suggest that the NO synthase/NO-dependent modulation of the Frank-Starling
      mechanism in fish is sensitive to thermal stress.

PMID- 23123762
TI  - Fluorescent differentiation and quantificational detection of free tryptophan in
      serum within a confined metal-organic tetrahedron.
AB  - A metal-organic cerium tetrahedron having size constraints and cooperated
      interactions within its cavity was used to selectively recognize tryptophan over
      other natural amino acids and Trp-containing peptides. It was applied in
      quantificational detection of free tryptophan in serum.

PMID- 23123763
TI  - Dietary fats and other nutrients on stroke.
AB  - PURPOSE OF REVIEW: This review summarizes current epidemiologic evidence
      regarding the associations of dietary fat and other nutrients with risk of
      stroke. RECENT FINDINGS: Recent epidemiologic studies show no association of
      total fat intake or absolute intakes of saturated, monounsaturated, or
      polyunsaturated fat with risk of stroke. Data on long-chain omega-3
      polyunsaturated fatty acids in relation to stroke risk are inconclusive but may
      favor fewer strokes in women. Insufficient evidence exists for trans fatty acids,
      other fatty acids, and dietary cholesterol intake. Present evidence indicates
      that high dietary magnesium and potassium intakes may lower the risk of stroke,
      whereas a high sodium (salt) intake and a low dietary vitamin D intake likely
      increase stroke risk. Calcium does not prevent stroke in populations with
      moderate-to-high calcium intakes but might play a role in populations with low
      calcium intakes. Supplementation with single vitamins likely has no protective
      effect on stroke in well nourished populations. SUMMARY: Available epidemiologic
      evidence indicates that diets high in magnesium and potassium may play a role in
      the prevention of stroke, whereas a high sodium intake is a risk factor. It
      remains unclear whether specific fatty acids, dietary cholesterol, and
      combinations of vitamins affect the risk of stroke.

PMID- 23123764
TI  - Microsome-associated lumenal lipid droplets in the regulation of lipoprotein
      secretion.
AB  - PURPOSE OF REVIEW: Liver is the major organ in mammals that possesses the
      capacity to release triglyceride within VLDL. VLDL assembly requires
      apolipoprotein (apo) B-100 with the assistance of microsomal triglyceride
      transfer protein (MTP), which facilitates the mobilization of triglyceride into
      the microsomal lumen. Recent experimental evidence has suggested that the lumenal
      triglyceride associated with endoplasmic reticulum (ER)/Golgi may represent an
      entity serving as precursors for large VLDL1. RECENT FINDINGS: Under lipid-rich
      conditions, discrete triglyceride-rich lipidic bodies, termed lumenal lipid
      droplets, are accumulated in association with ER/Golgi microsomes. Formation of
      the microsome-associated lumenal lipid droplets (MALD) is dependent on the
      activity of MTP, and the resulting apoB-free lipidic body is associated with a
      variety of proteins including apolipoproteins that are components of VLDL.
      Formation and utilization of MALD during the assembly and secretion of VLDL1 have
      a profound influence on hepatic cell physiology, such as ER stress responses.
      SUMMARY: This review summarizes current understanding of hepatic triglyceride
      homeostasis in general, and highlights the functional significance of
      triglyceride compartmentalization between cytosol and microsomes in particular.
      Understanding of MALD metabolism may shed new light on the prevention and
      treatment of liver diseases associated with abnormally elevated intracellular
      triglycerides.

PMID- 23123765
TI  - Identifying Community Needs and Resources in a Native Community: A Research
      Partnership in the Pacific Northwest.
AB  - Indigenous communities have engaged in needs and resources assessments for
      thousands of years. By blending CBPR/TPR approaches with community-driven assets
      and needs assessments, academic and community based researchers can work together
      to better understand and identify community strengths as well as issues of
      concern in Native communities. This best practice approach can set research
      agendas that are relevant to Native communities and result in interventions and
      health promotion programs that are respectful of Tribal sovereignty and that
      incorporate unique traditions and strengths of Native communities. A successful
      research partnership to develop and implement a needs and resources assessment
      using CBPR/TPR approaches is presented using a case study that can be used as a
      model for other research partnerships.

PMID- 23123766
TI  - High prevalence of epigenetic inactivation of the human four and a half LIM
      domains 1 gene in human oral cancer.
AB  - The four and a half LIM domains 1 (FHL1) gene has been related to carcinogenesis.
      However, the expression status of FHL1 in human oral squamous cell carcinoma
      (OSCC) remains unclear and the detailed mechanism of gene silencing is poorly
      understood. The aim of this study was to examine the FHL1 expression level and
      its regulatory mechanism in OSCCs. Quantitative reverse-transcriptase-polymerase
      chain reaction (PCR) and western blotting showed significant downregulation of
      FHL1 in all OSCC-derived cell lines (Sa3, HSC-2, HSC-3, HSC-4, HO-1-u-1, HO-1-N
      1, KON and Ca9-22) compared to human normal oral keratinocytes. We also found
      that FHL1 mRNA expression was frequently downregulated (P<0.01) in 51 (86.4%) of
      59 primary OSCCs compared with the corresponding normal oral tissues, while there
      was no significant difference between the status of the FHL1 protein expression
      in OSCCs and the clinicopathological features. Using methylation-specific PCR, we
      detected methylated FHL1 in all cell lines and treatment with the DNA
      methyltransferase inhibitor, 5-aza-2'-deoxycytidine restored the FHL1 expression.
      However, no significant restoration of FHL1 expression was observed using sodium
      butyrate, an inhibitor of histone deacetylase and chromatin immunoprecipitation
      showed that histone H3 lysine 9 in the FHL1 promoter region was significantly
      acetylated. In addition, no mutation in the entire coding region of the FHL1 gene
      was found. Therefore, our data suggested that inactivation of the FHL1 gene is a
      frequent event during oral carcinogenesis and that the mechanism of FHL1
      downregulation in OSCCs is through DNA methylation of the promoter region rather
      than histone deacetylation or mutation.

PMID- 23123767
TI  - Three minimally invasive methods of measuring of portal vein pressure in healthy
      dogs.
AB  - We compared wedged hepatic venous pressure (WHVP), splenic pulp pressure (SPP)
      and trans-splenic portal vein pressure (TSPVP) in healthy dogs. We found that
      portal blood pressure could be measured in dogs using any of these techniques.
      The WHVP, SPP and TSPVP were 7.8 +/- 1.0, 6.2 +/- 0.8 and 6.8 +/- 1.2 mmHg,
      respectively. Measuring SPP using ultrasound is most simple and minimally
      invasive, and it might be useful for evaluating portal hypertension in dogs with
      liver diseases.

PMID- 23123768
TI  - Simple ectopic kidney in three dogs.
AB  - Simple ectopic kidney was diagnosed in three dogs by means of radiography and
      ultrasonography. A 2-year-old castrated male Schnauzer, a 13-year-old female
      Schnauzer and a 9-year-old male Jindo were referred with vomiting, hematuria and
      ocular discharge, respectively. In all three dogs, oval-shaped masses with soft
      tissue density were observed in the mid to caudal abdomen bilaterally or
      unilaterally, and kidney silhouettes were not identified at the proper anatomic
      places on abdominal radiographs. Ultrasonography confirmed the masses were
      malpositioned kidney. The ectopic kidneys had relatively small size, irregular
      shape and short ureter but showed normal function on excretory urography.

PMID- 23123769
TI  - Magnetization dynamics in rare earth Gd3+ doped Mn(0.5)Zn(0.5)Fe2O4 magnetic
      fluid: electron spin resonance study.
AB  - The electron spin resonance (ESR) technique has been applied to study the spin
      dynamics in broad temperature range for rare earth doped
      Mn(0.5)Zn(0.5)Fe(1.9)Gd(0.1)O(4) (MZG5) magnetic fluid. Zero field cooled (ZFC)
      ESR spectra of MZG5 fluid exhibit an isotropic shift in the resonance field below
      40 K, while the field cooled (FC) ESR spectra show a deviation from sin(2)theta
      behavior and an angle dependent hysteresis, this unambiguously points to the
      dominating unidirectional freezing of surface spins below 40 K. Above 60 K, the
      resonance field exhibits sin(2)theta behavior, indicating the uniaxial anisotropy
      contribution of core spin. This indicates that surface spin freezing temperature
      is around 40 K. The presence of surface spin freezing and the coupling between
      core and surface spins are further supported by cycle dependent FC ESR spectra
      measured at 20 K, which show the systematic increase in resonance field (H(res))
      and intensity. The double peak behavior of blocking temperature distribution
      retrieved from ZFC-FC magnetization measurement is an additional corroboration of
      the existence of surface spin glass like layer.

PMID- 23123770
TI  - Frequency dependence of electron spin relaxation times in aqueous solution for a
      nitronyl nitroxide radical and perdeuterated-tempone between 250 MHz and 34 GHz.
AB  - Electron spin relaxation times of perdeuterated tempone (PDT) 1 and of a nitronyl
      nitroxide (2-(4-carboxy-phenyl)-4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl) 2
      in aqueous solution at room temperature were measured by 2-pulse electron spin
      echo (T(2)) or 3-pulse inversion recovery (T(1)) in the frequency range of 250
      MHz to 34 GHz. At 9 GHz values of T(1) measured by long-pulse saturation recovery
      were in good agreement with values determined by inversion recovery. Below 9 GHz
      for 1 and below 1.5 GHz for 2,T(1)~T(2), as expected in the fast tumbling regime.
      At higher frequencies T(2) was shorter than T(1) due to incomplete motional
      averaging of g and A anisotropy. The frequency dependence of 1/T(1) is modeled as
      the sum of spin rotation, modulation of g and A-anisotropy, and a thermally
      activated process that has maximum contribution at about 1.5 GHz. The spin
      lattice relaxation times for the nitronyl nitroxide were longer than for PDT by a
      factor of about 2 at 34 GHz, decreasing to about a factor of 1.5 at 250 MHz. The
      rotational correlation times, tau(R) are calculated to be 9 ps for 1 and about 25
      ps for 2. The longer spin lattice relaxation times for 2 than for 1 at 9 and 34
      GHz are due predominantly to smaller contributions from spin rotation that arise
      from slower tumbling. The smaller nitrogen hyperfine couplings for the nitronyl 2
      than for 1 decrease the contribution to relaxation due to modulation of A
      anisotropy. However, at lower frequencies the slower tumbling of 2 results in a
      larger value of omegatau(R) (omega is the resonance frequency) and larger values
      of the spectral density function, which enhances the contribution from modulation
      of anisotropic interactions for 2 to a greater extent than for 1.

PMID- 23123771
TI  - An Indian butyrylcholinesterase variant L307P is not structurally stable: a
      molecular dynamics simulation study.
AB  - The human butyrylcholinesterase (BChE) activity is less than 1% in the serum of
      silent variant individuals of Vysya community in India. They are homozygous for a
      point mutation at codon 307 (CTT -> CCT) resulting in the substitution of leucine
      307 by proline. The reason for the disappearance of the protein in the serum has
      not been explicated till date. Based on this background, we performed molecular
      dynamics simulation to probe the structural stability of Indian variant (L307P)
      in comparison with wild and other BChE variants (D70G, E497V, V142M) having
      differential esterase activity. The simulation of all the mutants except D70G
      showed a much larger Calpha root mean square deviation from the wild BChE crystal
      structure, showing the overall conformational disturbance. Further analysis
      revealed that secondary structure of the mutant proteins was not stable. The
      orientation of the catalytic triad is also distorted in all the mutants. The
      distance between delta nitrogen of His438 to epsilon oxygen of Glu325 and epsilon
      nitrogen of His438 to gamma oxygen of Ser198 were highly altered in L307P mutant
      than the wild and other three variants throughout the simulation. Such disparity
      of distances between the catalytic residues may be due to the change in the
      protein conformation attributing to their differential catalytic activity. Our
      studies thus prove that the Indian BChE L307P mutant with negligible activity is
      possibly due to its structural instability when compared to other BChE variants.

PMID- 23123772
TI  - Serotonin 2C receptor alternative splicing in a spinal cord injury model.
AB  - Spinal cord injury can have debilitating consequences, commonly resulting in
      motor dysfunction below the lesion site and the development of chronic pain
      syndromes. The serotonin pathway is important for inhibiting noxious stimuli and
      facilitating motor function after spinal cord injury. The serotonin 2C receptor
      (5HTR2C) has several characteristic features, and is regulated by the amount of
      serotonin 2C receptor as well as RNA editing and alternative splicing. In this
      study, we used a rat model of spinal contusion injury to investigate the
      relationship between the pain threshold and 5HTR2C alternative splicing. The pain
      threshold was assessed using mechanical stimulation with von Frey filaments. We
      then used real-time PCR to examine the RNA levels of 5HTR2C in three sections of
      the spinal cord: the rostral, injury-core, and caudal positions. On postoperative
      day 12, the pain threshold in injured rats was significantly reduced compared
      with sham-operated and naive rats. The total 5HTR2C levels were significantly
      lower in injured rats than in naive rats at all positions, and significantly
      lower in injured rats compared with sham-operated rats at injury-core and caudal
      positions. The ratio of exon Vb-skipped nonfunctional 5HTR2C mRNA to total 5HTR2C
      was significantly higher in injured rats compared with naive rats at the injury
      core and caudal positions, and significantly higher in injured rats compared with
      sham-operated rats at the caudal position. These results indicate that spinal
      contusion injury, which causes neuropathic pain, induces serotonergic
      dysfunction. This dysfunction appears to be mediated by decreased 5HTR2C mRNA
      expression, and alternative splicing. These results confirm the importance of
      considering splice variants when examining 5HTR2C.

PMID- 23123773
TI  - Magnetoencephalography assessment of evoked magnetic fields and cognitive
      function in subcortical ischemic vascular dementia patients.
AB  - OBJECTIVE: To investigate the relationship between cognitive impairment and
      somatosensory evoked magnetic field and auditory evoked magnetic field changes in
      elderly male patients with subcortical ischemic vascular dementia (SIVD).
      METHODS: Magnetoencephalography (MEG) was used to record evoked magnetic field
      changes from 4 SIVD patients (76-88 years), 3 patients with vascular cognitive
      impairment with no dementia (VCI-ND; 74-87 years), and 6 healthy volunteers (72
      85 years). Latency peaks, equivalent current dipole (ECD) strength, and bilateral
      ECD position were recorded. The MEG data were superimposed on magnetic resonance
      imaging to produce magnetic source imaging. RESULTS: Compared to controls, SIVD
      patients showed increased M20 latency and ECD strength. There were no significant
      differences in M20 inter-hemispheric positions across diagnostic categories. At
      M100, SIVD patients showed delayed auditory evoked magnetic field latency
      compared to controls. However, ECD strength and 3-dimensional inter-hemispheric
      differences were similar across the groups at the M100 measurement. CONCLUSIONS:
      Changes in somatosensory and auditory evoked magnetic field changes correlated
      with cognitive impairment in SIVD patients. Magnetic field latency measures may
      provide an objective and sensitive index for early dementia detection and
      monitoring of cognitive function.

PMID- 23123775
TI  - Contribution of the spinal P2X7 receptors to bee venom-induced nociception and
      inflammation in conscious rats.
AB  - Recently, P2X7 receptor (P2X7R) has been found to contribute to the development
      of inflammatory pain, however, the role of spinal P2X7R is not clear. The present
      study was designed to determine the roles of spinal P2X7R in the bee venom (BV)
      model, characterized by multiple pain-related behaviors and obvious inflammatory
      edema. We determined the effects of P2X7R antagonist A438790 on BV-induced PSN,
      mechanical allodynia and inflammatory swelling. Pre-treatment with intrathecal
      administration of A438079 significantly inhibited BV-induced PSN and mechanical
      allodynia in a dose-dependent manner, but had no effect on BV-induced
      inflammatory swelling. These data suggest that the activation of spinal P2X7Rs
      may play a key role in BV-induced nociception, but not inflammation.

PMID- 23123774
TI  - Anxiety correlates to decreased blood and prefrontal cortex IGF-1 levels in
      streptozotocin induced diabetes.
AB  - It is well known that diabetes mellitus may cause neuropsychiatric disorders such
      as anxiety disorders. Diabetes may also cause reduced IGF-1 (insulin like growth
      factor-1) levels in brain and blood. The purpose of the present study was to
      investigate the relationship between diabetes induced anxiety and IGF-1 levels in
      diabetic rats. The anxiety levels of rats were assessed 2 weeks after
      intraperitoneal injection of streptozotocin. Diabetic rats had higher levels of
      anxiety, as they spent more time in closed branches in elevated-plus-maze-test
      and less time in the center cells of open-field-arena. Prefrontal cortex (PFC)
      IGF-1 levels and neuron numbers were decreased and apoptosis was increased in
      diabetic rats. Blood IGF-1 levels decreased in a time dependent fashion following
      streptozotocin injection while blood corticosterone levels increased. They had
      higher malondialdehyde levels and lower superoxide dismutase enzyme activity.
      Oxidative stress may negatively affect blood and PFC tissue IGF-1 levels.
      Reduction in IGF-1 may cause PFC damage, which may eventually trigger anxiety in
      diabetic rats. Therapeutic strategies that increase blood and brain tissue IGF-1
      levels may be promising to prevent psychiatric sequelae of diabetes mellitus.

PMID- 23123776
TI  - Neuregulin-1 receptor tyrosine kinase ErbB4 is upregulated in midbrain
      dopaminergic neurons in Parkinson disease.
AB  - Previously we demonstrated that systemically administered neuregulin-1-beta1, a
      nerve growth and differentiation factor, passed the blood-brain barrier and
      accumulated in brain areas with expression of its receptor ErbB4. In substantia
      nigra (SN), neuregulin-1-beta1 phosphorylated ErbB4 and protected dopaminergic
      neurons in a toxin-based mouse model of Parkinson disease (PD). We studied ErbB4
      in the context of human midbrain dopaminergic degeneration in vivo and in vitro.
      Post-mortem ventral midbrain tissue sections of neuropsychiatric healthy
      individuals and PD patients (matched for age, gender and post-mortem delay) were
      immunostained for ErbB4. Cultured Lund human mesencephalic (LUHMES) post-mitotic
      dopaminergic neurons were treated with dopaminergic toxins and analyzed for ErbB4
      expression. In control individuals, 85.0+/-5.0% of dopaminergic neurons,
      containing cytoplasmic neuromelanin, expressed ErbB4 in the SN. In PD cases, the
      percentage of ErbB4-positive nigral dopaminergic neurons was increased to 94.9+/
      2.5%. The mean ErbB4 immunoreactivity of melanized neurons was higher in PD than
      controls. LUHMES neurons upregulated ErbB4 when exposed to toxins 1-methyl-4
      phenylpyridinium and 6-hydroxydopamine. Increased rate of ErbB4-positive
      dopaminergic neurons in PD may either reflect a better survival of ErbB4-positive
      neurons or an increased expression of ErbB4 by remaining neurons to seek trophic
      support. Enhanced ErbB4 expression in human in vitro toxin-based PD models
      supports the latter interpretation. Thus, dopaminergic neurons in SN might be
      susceptible to neuregulin-1 treatment in PD.

PMID- 23123777
TI  - Posture-related modulations in motor cortical excitability of the proximal and
      distal arm muscles.
AB  - The effect of postural orientation on the motor corticospinal excitability (MCE)
      of proximal and distal upper extremity (UE) muscles was investigated. In a
      crossover design, recruitment curves (RCs), short interval cortical inhibition
      (SICI) and intracortical facilitation (ICF) of resting anterior deltoid (AD) and
      first dorsal interosseus (FDI) was assessed in two postures: sitting and
      standing. Six healthy adults without contraindications to transcranial magnetic
      stimulation (TMS) participated in the study. TMS was applied over the motor
      cortical representation of FDI and AD at intensities ranging from 90% to 200% of
      resting motor threshold (RMT) in increments of 10%. SICI and ICF were assessed
      for each muscle using a conditioning stimulus (80% RMT) preceding a test stimulus
      (120% RMT) with an interstimulus interval of 2 ms and 15 ms, respectively. For
      AD, but not FDI, there was a significant and consistent increase in RC slope
      during standing compared to sitting. For FDI, there was no difference in ICF and
      SICI between sitting and standing. However, for AD, while there was no difference
      in ICF between the two postures, there was a clear trend for SICI to decrease
      (p=0.06) in standing compared to sitting. These results indicate that postural
      change from sitting to standing, affects the MCE of proximal but not distal
      muscles. While this indicates the role of proximal UE muscles in postural
      control, it also implies that rehabilitation protocols for enhancing proximal arm
      motor function may be advantaged if administered in a standing posture.

PMID- 23123778
TI  - Heterozygous mutations in the FGF8, SHH and nodal/transforming growth factor beta
      pathways do not confer increased dopaminergic neuron vulnerability--a zebrafish
      study.
AB  - Fibroblast growth factor 8 (FGF8), sonic hedgehog (SHH) and nodal signalling
      pathways play key roles in both development and survival of dopaminergic neurons.
      Both heterozygous mutations in autosomal recessively inherited Parkinson's
      disease (PD) genes such as parkin or PINK1 and exposure to exogenous toxins are
      thought to contribute to the pathogenesis of PD. The aim of our study was to
      investigate whether heterozygote mutations in fgf8, shh or oep lead to a reduced
      number of ascending dopaminergic neurons in zebrafish (Danio rerio) or confer
      increased susceptibility to the PD neurotoxin 1-methyl-4-phenyl-pyridinium
      (MPP+). At 3 days post fertilization, heterozygous mutations in fgf8, shh or oep
      did not affect the number of ascending dopaminergic neurons, nor did heterozygous
      mutations in fgf8, shh or oep result in increased susceptibility to MPP+. Further
      work is needed to determine whether haploinsufficiency in other
      neurodevelopmental genes might confer increased susceptibility to PD-related
      pathomechanisms.

PMID- 23123780
TI  - GABArho expression in the medial nucleus of the trapezoid body.
AB  - The Calyx of Held (CoH) synapse is the largest synapse in mammals. It is located
      in the medial nucleus of the trapezoid body (MNTB) and forms part of the auditory
      pathway. Modest GABAergic signaling is present in the CoH before hearing onset,
      when glutamatergic transmission predominates. In mice, after postnatal day 12,
      the absolute strength of glycinergic transmission increases markedly, while
      GABAergic signaling remains constant. The persistent GABAergic transmission in
      the MNTB is mediated by a slowly desensitizing component. In this study we
      recorded GABA-mediated responses from postsynaptic principal neurons (PPNs) of
      the MNTB and found that they are sensitive to TPMPA, suggesting the involvement
      of GABArho subunits. RT-PCR and immunohistofluorescence in the MNTB confirmed
      GABArho expression in PPNs. Interestingly, GABArho3 was present only before
      hearing onset, and there was a switch to GABArho1 and GABArho2 expression in
      adult animals.

PMID- 23123779
TI  - Mapping joint grey and white matter reductions in Alzheimer's disease using joint
      independent component analysis.
AB  - Alzheimer's disease (AD) is a neurodegenerative disease concomitant with grey and
      white matter damages. However, the interrelationship of volumetric changes
      between grey and white matter remains poorly understood in AD. Using joint
      independent component analysis, this study identified joint grey and white matter
      volume reductions based on structural magnetic resonance imaging data to
      construct the covariant networks in twelve AD patients and fourteen normal
      controls (NC). We found that three networks showed significant volume reductions
      in joint grey-white matter sources in AD patients, including (1)
      frontal/parietal/temporal-superior longitudinal fasciculus/corpus callosum, (2)
      temporal/parietal/occipital-frontal/occipital, and (3) temporal
      precentral/postcentral. The corresponding expression scores distinguished AD
      patients from NC with 85.7%, 100% and 85.7% sensitivity for joint sources 1, 2
      and 3, respectively; 75.0%, 66.7% and 75.0% specificity for joint sources 1, 2
      and 3, respectively. Furthermore, the combined source of three significant joint
      sources best predicted the AD/NC group membership with 92.9% sensitivity and
      83.3% specificity. Our findings revealed joint grey and white matter loss in AD
      patients, and these results can help elucidate the mechanism of grey and white
      matter reductions in the development of AD.

PMID- 23123781
TI  - Novel presenilin-1 Y159F sequence variant associated with early-onset Alzheimer's
      disease.
AB  - BACKGROUND: Mutations in the gene for presenilin-1 cause familial, early-onset
      Alzheimer's disease. METHODS: We report the case of a 43-year-old woman
      presenting with progressive cognitive decline and a family history of early-onset
      dementia. Her workup included cerebrospinal fluid amyloid-beta, tau, and phospho
      tau levels, as well as genetic sequencing of genes implicated in familial
      Alzheimer's disease. RESULTS: Cerebrospinal fluid biomarkers were consistent with
      a diagnosis of Alzheimer's disease. A novel nucleotide sequence variant (A476T)
      was discovered in one allele for presenilin-1, corresponding to a missense
      tyrosine-to-phenylalanine change at codon 159 (Y159F). An affected maternal uncle
      carried the same allele. The sequence variant occurs in a conserved region of the
      gene near other previously reported mutations. CONCLUSIONS: This novel presenilin
      1 sequence variant cosegregated with early onset dementia in the proband and at
      least one other affected family member, and likely represents a mutation causing
      familial, early-onset Alzheimer's disease.

PMID- 23123782
TI  - Difference of neural connectivity for motor function in chronic hemiparetic
      stroke patients with intracerebral hemorrhage.
AB  - Difference of neural connectivity for motor function had been studied by
      observation of neural activity within gray matter and nucleus using functional
      neuroimaging techniques. Diffusion tensor imaging (DTI) by a probabilistic
      tracking is useful for exploration of structural connectivity in the brain. We
      attempted to investigate difference of neural connectivity for motor function of
      the affected hand in chronic hemiparetic patients with intracerebral hemorrhage
      (ICH). Forty-four patients with ICH and 31 normal control subjects were
      recruited. Diffusion tensor imaging was acquired using a sensitivity-encoding
      head coil at 1.5 T. Motor function was evaluated using the motricity index (MI)
      for hand and Modified Brunnstrom Classification (MBC). The presence or absence of
      a connection was confirmed between the precentral knob of the affected hemisphere
      and seven areas. Compared with healthy subjects, the patient group showed lower
      connectivity to the contralesional primary motor cortex, ipsilesional basal
      ganglia, ipsilesional thalamus, contralesional cerebellum, and ipsilesional
      medullary pyramid in the affected hemisphere (p<0.05). Connections to the
      ipsilesional basal ganglia, ipsilesional thalamus, and ipsilesional medullary
      pyramid showed positive correlation with MI and MBC (p<0.05). We found difference
      of neural connectivity for motor function between chronic hemiparetic patients
      with ICH and control subjects. Our results suggest that the motor function of the
      stroke patient is related to neural connectivity between the ipsilesional M1 and
      the ipsilesional medullary pyramid, ipsilesional basal ganglia, and ipsilesional
      thalamus.

PMID- 23123783
TI  - Different functional reorganization of motor cortex after transfer of the
      contralateral C7 to different recipient nerves in young rats with total brachial
      plexus root avulsion.
AB  - Clinically, contralateral C7 transfer is used for nerve reconstruction in
      brachial plexus injuries. Postoperatively, synchronous motions at the donor limb
      are noteworthy. This study studied if different recipient nerves influenced
      transhemispheric functional reorganization of motor cortex after this procedure.
      90 young rats with total root avulsion of the brachial plexus were divided into
      groups 1-3 of contralateral C7 transfer to anterior division of the upper trunk,
      to both the musculocutaneous and median nerves, and to the median nerve,
      respectively. After reinnervation of target muscles, number of sites for forelimb
      representations in bilateral motor cortices was determined by intracortical
      microstimulation at 1.5, 3, 6, 9, and 12 months postoperatively. At nine months,
      transhemispheric reorganization of nerves neurotized by contralateral C7 was
      fulfilled in four of six rats in group 1, one of six in group 2 and none in group
      3, respectively; at 12 months, that was fulfilled in five of six in group 1, four
      of six in groups 2 and 3, respectively. Logistic regression analysis showed that
      rate of fulfilled transhemispheric reorganization in group 1 was 12.19 times that
      in group 3 (95% CI 0.006-0.651, p=0.032). At 12 months, number of sites for
      hindlimb representations which had encroached upon original forelimb
      representations on the uninjured side was statistically more in group 3 than in
      group 2 (t=9.5, p<0.0001). It is concluded that contralateral C7 transfer to
      upper trunk or to both the musculocutaneous and median nerves induces faster
      transhemispheric functional reorganization of motor cortex than that to median
      nerve alone in rats.

PMID- 23123784
TI  - Rit GTPase regulates a p38 MAPK-dependent neuronal survival pathway.
AB  - Rit, along with Rin and Drosophila Ric, comprises the Rit subfamily of Ras
      related small GTPases. Although the cellular functions of many Ras family GTPases
      are well established, the physiological significance of Rit remains poorly
      understood. Loss of Rit sensitizes multiple mammalian cell lines and mouse
      embryonic fibroblasts (MEFs) derived from Rit(-/-) mice to oxidative stress
      mediated apoptosis. However, whether Rit-mediated pro-survival signaling extends
      to other cell types, particularly neurons, is presently unknown. Here, to examine
      these issues we generated a transgenic mouse overexpressing constitutively active
      Rit (Rit(Q79L)) exclusively in neurons, under control of the Synapsin I promoter.
      Active Rit-expressing hippocampal neurons display a dramatic increase in
      oxidative stress resistance. Moreover, pharmacological inhibitor studies
      demonstrate that p38 MAPK, rather than a MEK/ERK signaling cascade, is required
      for Rit-mediated protection. Together, the present studies identify a critical
      role for the Rit-p38 MAPK signaling cascade in promoting hippocampal neuron
      survival following oxidative stress.

PMID- 23123785
TI  - Saccadic inhibition of return can arise from late-stage execution processes.
AB  - Inhibition of return (IOR) is thought to improve the efficiency of visual search
      behaviour by biasing attention, eye movements, or both, toward novel stimuli.
      Previous research suggests that IOR might arise from early sensory, attentional
      or motor programming processes. In the present study, we were interested in
      determining if IOR could instead arise from processes operating at or during
      response execution, independent from effects on earlier processes. Participants
      made consecutive saccades (from a common starting location) to central arrowhead
      stimuli. We removed the possible contribution of early sensory/attentional and
      motor preparation effects in IOR by allowing participants to fully prepare their
      responses in advance of an execution signal. When responses were prepared in
      advance, we continued to observe IOR. Our data therefore provide clear evidence
      that saccadic IOR can result from an execution bias that might arise from
      inhibitory effects on motor output neurons, or alternatively from late
      attentional engagement processes.

PMID- 23123786
TI  - Speech-induced modulation of interhemispheric inhibition.
AB  - This study aimed to determine the effects of speech and mastication on
      interhemispheric inhibition between the right and left primary motor areas (M1s)
      by using transcranial magnetic stimulation (TMS). Motor-evoked potentials (MEPs)
      were recorded from the first dorsal interossei (FDIs) of each hand of 10 healthy
      right-handed subjects under 3 conditions: at rest (control), during mastication
      (non-verbal oral movement), and during speech (reading aloud). Test TMS was
      delivered following conditioning TMS of the contralateral M1 at various
      interstimulus intervals. Under all conditions, the MEPs in the left FDIs were
      significantly inhibited after conditioning of the left M1 (i.e. inhibition of the
      right M1 by TMS of the left hemisphere). In contrast, the left M1 was
      significantly inhibited by the right hemisphere only during the control and
      mastication tasks, but not speech task. These results suggest that speech may
      facilitate the activity of the dominant M1 via functional connectivity between
      the speech area and the left M1, or may modify the balance of interhemispheric
      interactions, by suppressing inhibition of the dominant hemisphere by the non
      dominant hemisphere. Our findings show a novel aspect of interhemispheric
      dominance and may improve therapeutic strategies for recovery from stroke.

PMID- 23123787
TI  - Chronic inhibition of glycogen synthase kinase-3 protects against rotenone
      induced cell death in human neuron-like cells by increasing BDNF secretion.
AB  - Mitochondrial dysfunction is a common feature of many neurodegenerative
      disorders. Likewise, activation of glycogen synthase kinase-3 (GSK-3) has been
      proposed to play an important role in neurodegeneration. This multifunctional
      protein kinase is involved in a number of cellular functions and we previously
      showed that chronic inhibition of GSK-3 protects neuronal cells against
      mitochondrial dysfunction-elicited cell death, through a mechanism involving
      increased glucose metabolism and the translocation of hexokinase II (HKII) to
      mitochondria. Here, we sought to gain deeper insight into the molecular basis of
      this neuroprotection. We found that chronic inhibition of GSK-3, either
      genetically or pharmacologically, elicited a marked increase in brain-derived
      neurotrophic factor (BDNF) secretion, which in turn conferred resistance to
      mitochondrial dysfunction through subcellular re-distribution of HKII. These
      results define a molecular pathway through which chronic inhibition of GSK-3 may
      protect neuronal cells from death. Moreover, they highlight the potential
      benefits of enhanced neurotrophic factor secretion as a therapeutic approach to
      treat neurodegenerative diseases.

PMID- 23123788
TI  - Sensitivity to posed and genuine displays of happiness and sadness: a fMRI study.
AB  - The ability to distinguish posed from genuine facial displays of emotion and to
      act accordingly is a fundamental social skill. To investigate the neural
      correlates underpinning this sensitivity, we compared changes in brain activity
      associated with judging posed and genuine facial displays of happiness and
      sadness using fMRI. Photographs of displays were presented to 7 right-handed
      females who judged whether the person was feeling the target emotion and made
      yes/no responses. Results showed activity increases during the observation of
      genuine compared to posed happy displays in the left medial superior frontal
      gyrus (BA 9) and the middle cingulate cortex bilaterally (BAs 24 and 31). The
      same comparison for sad displays showed increased activity in the left medial
      superior frontal gyrus (BA 8), and in the right middle and triangular inferior
      frontal gyri (both BA 46). Participants who exhibited higher sensitivity to sad
      displays showed larger activity difference in the left medial superior frontal
      gyrus (BA 8). The present study provides evidence of differential neural activity
      when judging posed versus genuine facial displays of emotions. Further research
      is required to elucidate how this might impact social affective neuroscience and
      in what ways genuine facial displays can enhance our understanding of emotion
      perception.

PMID- 23123789
TI  - Neurochemical coding compared between varicose axons and cell bodies of myenteric
      neurons in the guinea-pig ileum.
AB  - The discrete functional classes of enteric neurons in the mammalian
      gastrointestinal tract have been successfully distinguished on the basis of the
      unique combination of molecules and enzymes in their cell bodies ("chemical
      coding"). Whether the same chemical coding exists in varicose axons of different
      functional classes has not been systematically tested. In this study, we
      quantified the coexistence of markers that define classes of nerve cell bodies in
      the myenteric plexus of the guinea-pig ileum, in varicose axons of the same
      neurons. Profound differences between the combinations of immunohistochemical
      markers in myenteric nerve cell bodies and in their varicosities were identified.
      These discrepancies were particularly notable for classes of neurons that had
      previously been classified as cholinergic, based on immunoreactivity for choline
      acetyltransferase (ChAT) in their cell bodies. To detect cholinergic varicose
      axons of enteric neurons in this study, we used antiserum against the vesicular
      acetylcholine transporter (VAChT). ChAT-immunoreactivity has been reported to be
      consistently co-localized with 5-hydroxytryptamine (5-HT) in interneuronal cell
      bodies, yet only 29+/-5% (n=4) of 5-HT-immunoreactive varicosities contained
      vesicular acetylcholine transporter (VAChT). Somatostatin coexists with ChAT
      immunoreactivity in a class of descending interneuron but only 21+/-1% (n=4) of
      somatostatin-immunoreactive varicosities were VAChT-immunoreactive. Comparable
      discrepancies were also noted for non-cholinergic markers. The results suggest
      that chemical coding of cell bodies does not necessarily reflect chemical coding
      of varicose axon terminals and that the assumption that nerve cell bodies that
      contain ChAT are functionally cholinergic may be questionable.

PMID- 23123790
TI  - Dose-response effects of exercise on abdominal obesity and risk factors for
      cardiovascular disease in adults: study rationale, design and methods.
AB  - Although progress has been made to elucidate the effects of exercise as a
      strategy for reducing obesity and related cardiometabolic risk factors, the
      specific exercise exposures required to achieve optimal benefit continue to be
      the source of considerable uncertainty and debate. Despite the inference of a
      dose-dependent relationship between exercise and health benefit, absent from the
      literature are randomized trials that, without alteration in caloric intake,
      examine the separate effects of exercise dose and intensity on obesity and
      associated cardiometabolic risk. We will perform a randomized, controlled trial
      designed to study the separate effects of habitual exercise differing in dose
      (energy expenditure, kcal/session) and intensity (relative to VO(2)peak) on
      abdominal obesity and selected cardiometabolic risk factors. The primary outcomes
      are waist circumference and 2-hour glucose. We will randomly assign 320
      sedentary, abdominally obese men (N=160) and women (N=160) to one of 4
      conditions: 1) no-exercise control, 2) low volume, low intensity exercise, 3)
      high volume, low intensity exercise, and 4) high volume, high intensity exercise.
      Duration of all treatments will be 6 months. The findings from this study may
      help resolve the following unanswered questions, "For a given exercise dose does
      higher exercise intensity result in greater health benefits?" "For a given
      exercise intensity does higher exercise dose result in greater health benefits?".
      Identification of the separate effects of exercise dose and intensity on obesity
      and related cardiometabolic risk factors under controlled conditions is important
      for development of optimal, lifestyle-based strategies that can subsequently be
      tested in long-term effectiveness trials.

PMID- 23123792
TI  - Improved EMCCD gamma camera performance by SiPM pre-localization.
AB  - High spatial resolution gamma-imaging can be achieved with scintillator readout
      by low-noise, fast, electron-multiplying charge-coupled devices (EMCCDs).
      Previously we have shown that false-positive events due to EMCCD noise can be
      rejected by using the sum signal from silicon photomultipliers (SiPMs) mounted on
      the sides of the scintillator. Here we launch a next generation hybrid CCD-SiPM
      camera that utilizes the individual SiPM signals and maximum likelihood
      estimation (MLE) pre-localization of events to discriminate between true and
      false events in CCD frames. In addition, SiPM signals are utilized for improved
      energy discrimination. The performance of this hybrid detector was tested for a
      continuous CsI:Tl crystal at 140 keV. With a pre-localization accuracy of 1.06 mm
      (full-width-at-half-maximum) attained with MLE the signal-to-background ratio
      (SBR) was improved by a factor of 5.9, 4.0 or 2.2 compared to the EMCCD-only
      readout, at the cost of rejecting, respectively, 47%, 9% or 4% of the events.
      Combining the pre-localization and SiPM energy estimation improved the energy
      resolution from 50% to (19 +/- 3)% while maintaining the spatial resolution at
      180 um.

PMID- 23123791
TI  - Pragmatic exercise intervention for people with multiple sclerosis (ExIMS trial):
      study protocol for a randomised controlled trial.
AB  - Exercise is an effective intervention for improving function, mobility and health
      related quality of life in people with multiple sclerosis (PwMS). Questions
      remain however, regarding the effectiveness of pragmatic exercise interventions
      for evoking tangible and sustained increases in physical activity and long-term
      impact on important health outcomes in PwMS. Furthermore, dose-response
      relationships between exercise and health outcomes have not previously been
      reported in PwMS. These issues, and improved knowledge of cost effectiveness, are
      likely to influence key decisions of health policy makers regarding the
      implementation of exercise therapy as part of the patient care pathway for PwMS.
      Hence, the primary aim of this study is to investigate whether a 12-week tapered
      programme of supervised exercise, incorporating cognitive-behavioural techniques
      to facilitate sustained behaviour change, is effective for evoking improvements
      in physical activity and key health outcomes in PwMS over 9 months of follow-up.
      A total of 120 PwMS will be randomised (1:1) to either a 12-week pragmatic
      exercise therapy intervention or usual care control group. Participants will be
      included on the basis of a clinical diagnosis of MS, with an expanded disability
      status score (EDSS) between 1 and 6.5. Outcome measures, to be assessed before
      and after the intervention and 6 months later, will include physical activity,
      clinical and functional measures and health-related quality of life. In addition,
      the cost effectiveness of the intervention will be evaluated and dose-response
      relationships between physical activity and the primary/secondary outcomes in
      those with mild and more severe disease will be explored.

PMID- 23123793
TI  - Natural killer cells display impaired responses to toll like receptor 9 that
      support viral persistence in chronic hepatitis B.
AB  - Toll like receptors (TLR) are crucial mediators of innate immune responses, but
      their influence on natural killer (NK) cell function in chronic hepatitis B
      infection (CHB) is not well understood. Here we evaluated the responses of
      peripheral NK cells from CHB patients to multiple TLR agonists. CHB was
      associated with an impaired NK cell IFN-gamma response to TLR9 stimulation
      compared to controls. This deficiency corrected with recombinant IFN-alpha, while
      anti-IFN-alpha neutralizing antibody diminished NK IFN-gamma production in
      controls. NK cell CD69 upregulation in response to TLR9 was maintained in CHB. No
      differences were noted in responses to the other TLR ligands. Our results
      demonstrate a dichotomous NK cell response to TLR9 that is mediated by IFN-alpha
      and reflect the multiple mechanisms involved with NK activation. Consequently, it
      is possible that when activated these cells are unable to contribute to viral
      clearance while still having the potential to mediate tissue injury.

PMID- 23123794
TI  - Fresh ginger (Zingiber officinale) has anti-viral activity against human
      respiratory syncytial virus in human respiratory tract cell lines.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Ginger, Zingiber officinale Roscoe, is a common
      spice and also a widely used medicinal plant in ancient China. Ginger is an
      ingredient of Ge-Gen-Tang (Kakkon-to; GGT). GGT has been proved to have antiviral
      activity against human respiratory syncytial virus (HRSV). However, it is unknown
      whether ginger is effective against HRSV. AIM OF THE STUDY: To find a readily
      available agent to manage HRSV infection, the authors tested the hypothesis that
      ginger can effectively decrease HRSV-induced plaque formation in respiratory
      mucosal cell lines. MATERIALS AND METHODS: Effect of hot water extracts of fresh
      and dried gingers on HRSV was tested by plaque reduction assay in both human
      upper (HEp-2) and low (A549) respiratory tract cell lines. Ability of ginger to
      stimulate anti-viral cytokines was evaluated by enzyme-linked immunosorbent assay
      (ELISA). RESULTS: Fresh ginger dose-dependently inhibited HRSV-induced plaque
      formation in both HEp-2 and A549 cell lines (p<0.0001). In contrast, dried ginger
      didn't show any dose-dependent inhibition. 300 MUg/ml fresh ginger could decrease
      the plaque counts to 19.7% (A549) and 27.0% (HEp-2) of that of the control group.
      Fresh ginger was more effective when given before viral inoculation (p<0.0001),
      particularly on A549 cells. 300 MUg/ml fresh ginger could decrease the plaque
      formation to 12.9% when given before viral inoculation. Fresh ginger dose
      dependently inhibited viral attachment (p<0.0001) and internalization (p<0.0001).
      Fresh ginger of high concentration could stimulate mucosal cells to secrete IFN
      beta that possibly contributed to counteracting viral infection. CONCLUSIONS:
      Fresh, but not dried, ginger is effective against HRSV-induced plaque formation
      on airway epithelium by blocking viral attachment and internalization.

PMID- 23123795
TI  - Sex dependent pharmacokinetics, tissue distribution and excretion of peimine and
      peiminine in rats assessed by liquid chromatography-tandem mass spectrometry.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Fritillaria thunbergii Miq. has been
      traditionally used in China as antitussive and expectorant herbs, and newly used
      in the clinical treatment of leukemia in recent years. AIM: To investigate
      whether gender exerted a significant influence on the pharmacokinetics, tissue
      distribution and excretion of peimine and peiminine in Sprague-Dawley rats who
      were given a single oral administration of 4.25 g/kg Fritillaria thunbergii Miq.
      extract. MATERIALS AND METHODS: Sprague-Dawley rats were assigned into two groups
      based on the gender and orally administered 4.25 g/kg Fritillaria thunbergii Miq.
      extract for each individual pharmacokinetics, tissue distribution and excretion
      study. RESULTS: Compared with female rats, peimine and peiminine were eliminated
      slowly from male rat plasma, and significant gender-related differences were
      observed in the pharmacokinetic parameters. Drug blood and tissue levels in male
      rats were significantly higher than the female counterparts except for several
      tissues, such as fat, muscle and skin. Gender also exerted a significant
      influence on the urine excretion but such effect was not observed in the feces
      excretion study. CONCLUSIONS: Gender exerted a significant influence on the
      pharmacokinetics, tissue distribution and urine excretion of peimine and
      peiminine. It is assumed that the sex-associated differences of peimine and
      peiminine in rats might be mainly result from sex-dependent expression and
      activity of drug metabolism enzymes and P-glycoprotein.

PMID- 23123796
TI  - Influence of polysaccharide fractions isolated from Caltha palustris L. on the
      cellular immune response in collagen-induced arthritis (CIA) in mice. A
      comparison with methotrexate.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The extracts from Caltha palustris have been used
      in traditional Canadian and Asian medicine to treat arthritis and rheumatism.
      AIMS: The aim of the study was to investigate the anti-arthritis and
      immunomodulatory activity of the polysaccharide fractions B and C of Caltha
      palustris L. herbal extracts in collagen-induced arthritis (CIA) mice, an animal
      model of rheumathoid arthritis. The results were compared with those of
      methotrexate (MTX) treatment. MATERIALS AND METHODS: CIA was induced in male and
      female DBA/1J mice by intradermal injection of chicken type II collagen in
      Freund's complete adjuvant (cFA). Booster injection of collagen (in incomplete
      Freund's adjuvant) was given on day 21 of the experiment. Mice were treated daily
      for 21 consecutive days with investigated fractions B or C at a dose of 10mg/kg
      (the first dose was given 24h after the booster) or phosphate buffered saline
      (PBS) (negative and positive control group). MTX was administered in parallel,
      intraperitoneally at three weekly cycles-every 48 h for 3 weeks at a dose of 6.6
      mg/kg, the first dose was given on day 22 of the experiment. The severity of
      arthritis was evaluated by arthritic scores. Flow cytometry was used to
      investigate subsets of T lymphocytes in the thymus, and T and B lymphocytes in
      the spleen, and in mesenteric lymph nodes. T regulatory lymphocytes in the spleen
      were also quantified by means of flow cytometry. The levels of IL-2, IL-6, IL-10,
      IFN-gamma and TNF-alpha in serum were also measured. RESULTS: The results
      revealed that fraction B significantly reduced the severity of joint swelling and
      erythema to a similar degree as MTX. It was also found that B fraction and MTX
      inhibited leucocytosis in peripheral blood caused by CIA, however the inhibitory
      effect of MTX persisted longer than that of fraction B. The analysis of
      lymphocyte T subsets demonstrated that both investigated fractions and MTX caused
      a partial or complete normalization in the percentage and the absolute number of
      CD4(-)CD8(-) thymocytes (immature, double-negative cells), and increased the
      percentage of CD8(+) T cells in peripheral lymphoid organs of mice with CIA.
      Moreover, an increase in the percentage of CD4(+) thymic cells was observed after
      treatment with fraction B or MTX. Fraction C showed the weakest effect in
      normalization of the percentage and the absolute number of CD4(-)CD8(-) thymus
      lymphocytes in mice with CIA. The potency of fraction B was comparable to MTX. A
      significant decrease in the percentage and the absolute count of splenic T
      regulatory cells (CD4(+)CD25(+)FOXP3(+)) was observed after treatment with both
      Caltha palustris fractions. The inhibiting influence of investigated fractions on
      TNF-alpha serum concentration was significant and lasted longer in the case of
      fraction C. Production of other cytokines was modulated slightly (increase in IFN
      gamma) or markedly (decrease in IL-2). CONCLUSION: The results of the experiment
      suggested that the administration of polysaccharide B fraction from Caltha
      palustris extract significantly suppressed the progression of CIA. These results
      are similar to those obtained in the case of MTX treatment. This indicates that
      fraction B may be a potent candidate for botanical anti-arthritic agent.

PMID- 23123797
TI  - From popular use to pharmacological validation: a study of the anti-inflammatory,
      anti-nociceptive and healing effects of Chenopodium ambrosioides extract.
AB  - ETHNO-PHARMACOLOGICAL RELEVANCE: Chenopodium ambrosioides (Amarantaceae) is an
      annual or perennial plant popularly known as 'erva de Santa Maria', 'mastruco'
      and 'erva-do-formigueiro'. This herb is used in folk medicine in the form of
      teas, poultices and infusions for inflammatory problems, contusions and lung
      infections, and as an anthelmintic and anti-fungal. AIM OF THE STUDY: The aim of
      the present study was to further the understanding of the anti-nociceptive, anti
      inflammatory and wound healing effects of ethanol extract (EE) obtained from the
      leaves and stems of Chenopodium ambrosioides in animal models of acute pain,
      inflammation and wound healing, thus supporting its medicinal use for the
      treatment of pain and inflammatory conditions MATERIALS AND METHODS: The anti
      nociceptive activity of EE (150-500 mg/kg) was evaluated using the nociception
      induced by formalin (2.5%), prostaglandin-E(2) (PGE2; 3 nmol/paw), capsaicin
      (CAP, 1.6 MUg/paw) and bradykinin (BK, 10 nmol/paw). The anti-inflammatory
      activity of EE (150-500 mg/kg) was evaluated in carrageenan- (Cg, 300 MUg/paw),
      PGE(2)- (3 nmol/paw), substance P- (SP, 20 nmol/paw) and BK- (3 nmol/paw) induced
      paw oedema. The topical anti-inflammatory activity of EE (1%, 3% and 5%) was
      evaluated in arachidonic acid- (AA, 2mg/ear), oil croton- (1 MUg/ear) and CAP-
      (250 MUg/ear) induced ear oedema. The effect of this extract in the inhibition of
      the influx of neutrophil, myeloperoxidase (MPO) and adenosine-deaminase (ADA)
      activities and nitric oxide (NO) and TNF-a levels was also determined using the
      mouse of pleurisy induced by Cg. The excision wound model in rats was used to
      evaluate the wound healing efficacy of EE (1%, 3% and 5%). To exclude the
      possible non-specific muscle relaxant or sedative effects of EE, mice motor
      performance was also evaluated with the rota-rod test. RESULTS: EE (5% per ear)
      was effective in reducing ear oedema induced by croton oil by 78.09%, CAP by
      70.85% and AA by 77.02%. EE (500 mg/kg; p.o.) also significantly inhibited paw
      oedema induced by Cg by 40%, PGE(2) by 51%, SP by 56% and BK by 57%. EE (500
      mg/kg; p.o.) inhibited the cell influx of leucocytes by 78% and neutrophils by
      53%, MPO activity by 62.22% and ADA activity by 23.07%, as well as NO by 77.77%
      and TNF-a levels by 50% in the fluid leakage due to the carrageenan-induced
      pleurisy. EE also inhibited the formalin-induced nociceptive in both phases of
      pain (neurogenic and inflammatory) at a dose of 500 mg/kg, resulting in
      inhibitions of 77.39% and 95.60%, respectively. EE (500 mg/kg; p.o.) was also
      effective in inhibiting the nociception induced by PGE(2) (68%), CAP (53%) and BK
      (32%). Topical application of EE (5%) on excision wounds caused a significant
      reduction in wound area when compared with the untreated controls. Finally,
      treatment with EE (150-500 mg/kg) did not show any significant alterations in
      motor performance or body temperature compared with the control group.
      CONCLUSIONS: The results, including the inhibition of mediators (BK, NO, SP,
      PGE(2) and TNF-a) and enzyme (MPO and ADA) activity, validate the use of the
      plant under study for therapeutic treatment of anti-inflammatory, painful and
      wound healing processes.

PMID- 23123798
TI  - Anti-inflammatory, wound healing and in-vivo antioxidant properties of the leaves
      of Ficus amplissima Smith.
AB  - ETHNO PHARMACOLOGICAL RELEVANCE: Ficus amplissima, commonly known as kal-itchchi,
      being used in folklore medicine, leaves juice is applied externally on old
      chronic wounds and the latex is applied on the wound. AIM: There was no
      scientific evidence justifying the medicinal use of Ficus amplissima, therefore
      the present study was aimed at evaluation of anti-inflammatory, wound healing and
      in-vivo antioxidant activity of the plant. MATERIALS AND METHODS: In the present
      study the acetone extract of Ficus amplissima leaves were studied for enzymatic
      antioxidant activity through different assays, anti-inflammatory by using
      carrageenan and histamine induced rat paw edema models (50mg, 100mg acetone
      extract) and wound healing activity by incorporating the two doses (1% (w/w) and
      2% (w/w)) of acetone extract and simple ointment base B.P. in concentration of
      0.5% (w/w) using excision and incision wound models in rats. In case of the
      excision wound model wound contraction and period of epithelization was studied
      while incision wound model was evaluated by determining tensile strength.
      RESULTS: Ficus amplissima leaves expressed the potent anti-inflammatory and in
      vivo antioxidant activity where 100mg acetone extract showed high activity.
      Treatment of wound with ointment containing 2% (w/w) acetone extract exhibited
      significant (P<0.001) wound healing activity. CONCLUSION: The acetone extract of
      Ficus amplissima leaves exhibited better anti-inflammatory, wound healing and in
      vivo antioxidant activity probably due to phenols constituents.

PMID- 23123799
TI  - Antiophidic activity of the extract of the Amazon plant Humirianthera ampla and
      constituents.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Although serotherapy against snakebite has been
      discovered more than one hundred years ago, antivenom is not available all over
      Brazil. The use of plants from folk medicine is common mainly in the Brazilian
      Amazon area. One of these plants is named Humirianthera ampla (HA). MATERIALS AND
      METHODS: We have investigated HA extract and constituents' antiophidic activity
      in different experimental protocols against some Bothrops snake venoms (Bothrops
      jararacussu, Bothrops atrox and Bothrops jararaca). The protocols investigated
      include phospholipase, proteolytic, pro-coagulant, hemorrhagic, edematogenic and
      myotoxic activities induced by these venoms in Swiss mice. RESULTS: All the
      venoms caused an increase in the rate of creatine kinase (CK) release from
      isolated muscles, indicating damage to the sarcolemma. The crude extract of HA
      decreased the myotoxic activity in a concentration-dependent fashion. The
      presence of HA 300 MUg/mL decreased up to 96% of Bothrops jararacussu and 94% of
      Bothrops atrox myotoxicity after 90 min of exposure. In vivo myotoxicity of
      Bothrops atrox venom was decreased in 75% when the venom was preincubated with HA
      500 mg/kg. Similar results were observed with lupeol against Bothrops jararacussu
      and Bothrops atrox venoms. The hemorrhagic activity was evaluated by intradermal
      injection of Bothrops atrox venom. Preincubation and oral pre- and posttreatment
      with HA decreased hemorrhage by 100%, 45% and 45%, respectively. Bothrops atrox
      venom also induced formation of edema, which was significantly inhibited by pre-
      and posttreatment with HA. All the venoms showed extensive pro-coagulating
      properties, and these activities were inhibited by up to 90% with HA, which
      presented concentration-dependent inhibition. Finally, proteolytic and
      phospholipase activities of the venoms were all inhibited by increasing
      concentrations of HA, lupeol and sitosterol. The inhibition of these activities
      might help explain the actions against in vivo myotoxicity and the in vivo
      effects observed, i.e., edema, myotoxicity, pro-coagulation and hemorrhage.
      CONCLUSIONS: Altogether, our results give support for the popular use of HA
      extracts in cases of accidents with snakes, suggesting that it can be used as an
      adjunct in the management of venomous snakebites.

PMID- 23123800
TI  - Encapsulation of yeast displaying glucose oxidase on their surface in graphene
      oxide hydrogel scaffolding and its bioactivation.
AB  - Yeast displaying glucose oxidase on their surface were encapsulated in a graphene
      oxide hydrogel. The ability of the modified yeast to reduce graphene oxide by
      glucose assimilation while maintaining viability was tested with time and deemed
      suitable for biofuel cell applications.

PMID- 23123801
TI  - Surface ion transfer growth of ternary CdS(1-x)Se(x) quantum dots and their
      electron transport modulation.
AB  - We report a surface ion transfer method to synthesise ternary alloy CdS(1-x)Se(x)
      (0 <=x<= 1) quantum dots (QDs) in situ on TiO(2) nanoparticles. By tuning the
      content of selenium in such quantum dots, the optical absorption spectra can be
      controllably widened to cover the most of the visible light range. The electron
      transport of such QDs can be modulated by changing the interfacial electronic
      energy between CdS(1-x)Se(x) QDs and TiO(2) nanoparticles. The QDs with optimized
      selenium content (x = 0.72) give a balance between a broad optical absorption and
      a suitable energy band alignment. The homogenous alloy CdS(1-x)Se(x) QDs achieve
      a maximum light-harvesting efficiency over 90%, and generate a photocurrent
      density larger than 10 mA cm(-2), which is 2.6- and 1.4-times that of binary CdS
      and CdSe QDs sensitized photovoltaic devices.

PMID- 23123802
TI  - The role of REM sleep in the processing of emotional memories: evidence from
      behavior and event-related potentials.
AB  - Emotional memories are vividly remembered for the long-term. Rapid eye movement
      (REM) sleep has been repeatedly proposed to support the superior retention of
      emotional memories. However, its exact contribution and, specifically, whether
      its effect is mainly on the consolidation of the contents or the processing of
      the affective component of emotional memories is not clear. Here, we investigated
      the effects of sleep rich in slow wave sleep (SWS) or REM sleep on the
      consolidation of emotional pictures and the accompanying changes in affective
      tone, using event-related potentials (ERPs) together with subjective ratings of
      valence and arousal. Sixteen healthy, young men learned 50 negative and 50
      neutral pictures before 3-h retention sleep intervals that were filled with
      either SWS-rich early or REM sleep-rich late nocturnal sleep. In accordance with
      our hypothesis, recognition was better for emotional pictures than neutral
      pictures after REM compared to SWS-rich sleep. This emotional enhancement after
      REM-rich sleep expressed itself in an increased late positive potential of the
      ERP over the frontal cortex 300-500 ms after stimulus onset for correctly
      classified old emotional pictures compared with new emotional and neutral
      pictures. Valence and arousal ratings of emotional pictures were not
      differentially affected by REM or SWS-rich sleep after learning. Our results
      corroborate that REM sleep contributes to the consolidation of emotional contents
      in memory, but suggest that the affective tone is preserved rather than reduced
      by the processing of emotional memories during REM sleep.

PMID- 23123804
TI  - Natural variation in enzyme activity of the African cichlid Pseudocrenilabrus
      multicolor victoriae.
AB  - This study describes the metabolic capacities of the African cichlid
      Pseudocrenilabrus multicolor victoriae from four sites in Uganda, East Africa.
      Fish were captured during the dry season, from two aquatic systems in different
      regions (Lake Nabugabo and Mpanga River). Within the Lake Nabugabo region,
      individuals were sampled from Lake Kayanja (normoxic) and Lwamunda Swamp
      (hypoxic); within the Mpanga River system, individuals were sampled from Bunoga
      and Kahunge (characterized by seasonal variation in dissolved oxygen (D.O.)).
      Enzyme activity levels of pyruvate kinase, lactate dehydrogenase, citrate
      synthase, and cytochrome C oxidase were measured in four tissues: white skeletal
      muscle, heart, brain, and liver. Two additional enzymes were measured in the
      liver, malate dehydrogenase and fructose 1,6-bisphosphatase. Regional differences
      between enzyme activities in most tissues were evident; however, little variation
      was observed between two sites within a region despite differences in D.O. In
      general, P. multicolor from the Mpanga River system displayed greater anaerobic
      enzyme activity in white skeletal muscle, lower gluconeogenic enzyme activity in
      the liver, and an overall higher enzyme activity in the heart and brain tissues
      than fish from the Nabugabo region. The latter may reflect a long-term adaptation
      to low-oxygen conditions at the metapopulation level in the Nabugabo region.

PMID- 23123803
TI  - Mice expressing the ADNFLE valine 287 leucine mutation of the Beta2 nicotinic
      acetylcholine receptor subunit display increased sensitivity to acute nicotine
      administration and altered presynaptic nicotinic receptor function.
AB  - Several mutations in alpha4 or beta2 nicotinic receptor subunits are linked to
      autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). One such missense
      mutation in the gene encoding the beta2 neuronal nicotinic acetylcholine receptor
      (nAChR) subunit (CHRNB2) is a valine-to-leucine substitution in the second
      transmembrane domain at position 287 (beta2VL). Previous studies indicated that
      the beta2VL mutation in mice alters circadian rhythm consistent with sleep
      alterations observed in ADNFLE patients (Xu et al., 2011). The current study
      investigates changes in nicotinic receptor function and expression that may
      explain the behavioral phenotype of beta2VL mice. No differences in beta2 mRNA
      expression were found between wild-type (WT) and heterozygous (HT) or homozygous
      mutant (MT) mice. However, antibody and ligand binding indicated that the
      mutation resulted in a reduction in receptor protein. Functional consequences of
      the beta2VL mutation were assessed biochemically using crude synaptosomes. A gene
      dose dependent increase in sensitivity to activation by acetylcholine and
      decrease in maximal nAChR-mediated [(3)H]-dopamine release and (86)Rb efflux were
      observed. Maximal nAChR-mediated [(3)H]-GABA release in the cortex was also
      decreased in the MT, but maximal [(3)H]-GABA release was retained in the
      hippocampus. Behaviorally both HT and MT mice demonstrated increased sensitivity
      to nicotine-induced hypolocomotion and hypothermia. Furthermore, WT mice display
      only a tonic-clonic seizure (EEG recordable) 3 min after injection of a high dose
      of nicotine, while MT mice also display a dystonic arousal complex (non-EEG
      recordable) event 30s after nicotine injection. Data indicate decreases in
      maximal response for certain measures are larger than expected given the decrease
      in receptor expression.

PMID- 23123806
TI  - The eyes of a tiny 'Orsten' crustacean - a compound eye at receptor level?
AB  - Among the oldest fossil crustaceans are those of the Late Cambrian (Furongian 499
      +/- 0.3-488.3 +/- 1.7 Ma) of Vastergotland, central Sweden and the lower
      Ordovician (Tremadocian 488.3 and 478.6 Ma) of the island of Oland. These are
      three-dimensionally preserved in nodules from the so called 'stinkstone'
      ('Orsten') limestone. 'Orsten'-like fossils represent tiny, often meiobenthic
      organsisms (Haug, Maas, & Waloszek, 2009) smaller than 2mm, which mainly were
      arthropods, especially crustaceans close to the stemline. As a result of
      phosphatisation, hairs, bristles and even cellular structures up to 0.3 MUm are
      preserved (Walossek, 1993), especially compound eyes, as typical for all visually
      orientated crustaceans (Schoenemann et al., 2011). We show a miniscule prototype
      of a compound eye (~40 MUm) in a small crustacean, which lived almost half a
      billion years ago. The eye is close to but comfortably established above being
      limited in its resolving power by diffraction, but it is too small to be an
      apposition eye, normally regarded as the basal form of all compound eyes, as is
      found in bees, dragonflies, crustaceans and many other arthropods still living
      today. The facets of this compound eye are ~8 MUm in size, the surface structure
      indicates the relicts of a tiny lens covering each facet. In order to work
      functionally and to ensure that that diffraction and waveguide problems were
      avoided, it seems reasonable to suppose that the compound eye consisted of visual
      units, each with a single photoreceptor cell directly below a weak lens for
      capturing and slightly focusing the light. The entire unit has a diameter similar
      to that of a normal sensory cell as found in compound eyes. Thus, the early
      compound eye analysed here may be interpreted as a prototype representing the
      earliest stages of the evolution of crustacean compound eyes.

PMID- 23123805
TI  - Kinesin-2 family motors in the unusual photoreceptor cilium.
AB  - This review focuses on recent advances in the understanding of kinesin-2 family
      motors in vertebrate photoreceptor development. Zebrafish photoreceptors develop
      by the 3rd day of embryogenesis, making it possible to study mutant phenotypes
      without the use of conditional alleles. Recent work using a zebrafish kif3b
      mutant allele validates the concept that the heterotrimeric kinesin II motor is
      generally required for ciliogenesis. In zebrafish photoreceptors, however, loss
      of kif3b function delays but does not block cilium formation. This is thought to
      occur because both kif3b or kif3c can dimerize with kif3a and function
      redundantly. The second ciliary kinesin thought to function in photoreceptor
      cells is kif17. Prior work has shown that either morpholino knockdown of this
      gene or the overexpression of its dominant negative form can reduce or delay
      photoreceptor cilium development without any evident impact on ciliogenesis in
      general. This has led to the idea that kif17 may play an important role only in
      some specialized cilium types, such the one in photoreceptor cells. In a recently
      identified kif17 mutant, however, photoreceptor outer segments are formed by 5
      dpf and an obvious delay of outer segment formation is seen only at the earliest
      stage analyzed (3 dpf). This work suggests that kif17 plays a significant role
      mainly at an early stage of photoreceptor development. Taken together, these
      studies lead to an intriguing concept that as they differentiate photoreceptors
      alter their kinesin repertoire.

PMID- 23123807
TI  - Cross-correlation in face discrimination.
AB  - An extensive body of literature suggests that face perception depends critically
      upon specialised face processing mechanisms. Although it seems clear that
      specialised face processing is required to explain face recognition, face
      discrimination is a simpler task that could possibly be solved with a general
      pattern discrimination mechanism. Observers were presented with face images that
      were either identical or not and judged whether they were the same or different.
      Face discrimination performance was well described by the point-by-point cross
      correlation between the face images, which is a simple mechanism of the type used
      for discriminating patterns such as gratings. This result held for male and
      female faces viewed frontally or in profile. Results for inverted and contrast
      reversed faces were also well described by cross-correlation, with observers
      having lowered efficiency relative to normal faces.

PMID- 23123808
TI  - Strain-induced suppression of weak localization in CVD-grown graphene.
AB  - We investigate the magnetic-field- and temperature-dependent transport properties
      of CVD-grown graphene transferred to a flexible substrate (Kapton) and subjected
      to externally applied strain. In zero magnetic field, a logarithmic temperature
      dependent conductivity correction, resulting from strong electron-electron
      interaction, becomes weaker with the application of strains as large as 0.6%
      because of an increased rate of chiral-symmetry-breaking scattering. With the
      application of a perpendicular magnetic field, we also observe positive
      magnetoconductance at low temperature (T = 5 K) due to weak localization. This
      magnetoconductance is suppressed with increasing strain, concomitant with a rapid
      decrease of the intervalley scattering rate (tau(i)(-1)). Our results are in good
      agreement with theoretical expectations and are consistent with a strain-induced
      decoupling between graphene and its underlying Kapton substrate.

PMID- 23123809
TI  - Professional standards within urology nursing.

PMID- 23123810
TI  - Patients' perspectives on timing of urinary catheter removal after surgery.
AB  - A prolonged catheter duration is a major risk factor for catheter-associated
      urinary tract infection, with bacteriuria increasing by 5% per day (Gokula et al,
      2004). AIM: In this study, the authors explored patients' perceptions of the care
      process relating to peri-operative catheterisation to identify patient factors
      that encourage early removal. METHOD: Semi-structured interviews, incorporating a
      grounded theory approach, were performed on three men and seven women during
      2010. Interviews were transcribed and analysed using constant comparative method
      and thematic framework analysis. RESULTS: Catheter duration ranged 1-10 days.
      Main themes elicited included: lack of understanding of the purpose and
      catheterisation process; loss of patient autonomy and dignity; and impact of
      environmental factors. CONCLUSION: Lack of knowledge of the catheterisation
      process among participants led to fears and concerns that may have contributed to
      delayed catheter removal. Changes to patient care that are likely to reduce
      catheter duration include ensuring the provision of pre-operative information,
      greater patient involvement in catheter removal decisions, and provision of
      easily accessible toilet facilities.

PMID- 23123811
TI  - Stress incontinence and pelvic floor exercises in pregnancy.
AB  - This literature review is a critique of the research looking at the impact of
      pelvic floor exercises during pregnancy on urinary stress incontinence in
      postnatal women. Seven studies were selected for review following a database
      search on the Cumulative Index to Nursing and Allied Health Literature (CINAHL),
      Embase, Medline and the British Nursing Index (BNI). The research produced mixed
      findings. Four of the seven studies demonstrated a significant improvement in
      urinary stress incontinence in postnatal women following pelvic floor muscle
      exercise during pregnancy. However, the studies that spanned a longer time period
      found no long-term effectiveness. More research is needed for a more conclusive
      picture as to whether antenatal pelvic floor exercises can improve stress
      incontinence in the postpartum period.

PMID- 23123812
TI  - Urinary incontinence in women.

PMID- 23123813
TI  - An overview of male  intermittent self-catheterisation.
AB  - Since the early 1970s intermittent self-catheterisation (ISC) has become
      increasingly popular and is now considered the method of choice for draining
      retained urine from the bladder and to treat urethral strictures in men. It is
      the preferred option for this kind of bladder dysfunction management instead of
      an indwelling urinary catheter. Learning ISC can be a challenging time for men,
      but with the support of knowledgeable experienced nurses in teaching ISC it can
      be successfully achieved. This article outlines the anatomy of the male urinary
      tract, offers practical tips for nurses who teach it, and highlights issues
      important to men when learning and living with ISC.

PMID- 23123814
TI  - Prostate cancer overview. Part 2: metastatic prostate cancer.
AB  - Advances in diagnosis mean that prostate cancer can be detected in the early
      stages, when options such as surgery and radiotherapy offer curative approaches
      and active surveillance is appropriate. However, advanced or metastatic disease
      continues to challenge medical management, which offers only palliative
      approaches. With such a prognosis, effective treatment of metastatic and
      metastatic castrate-resistant prostate cancer (mCRPC) is an important element of
      the management of these patients. The second article of this two-part series
      focuses on the main management approaches, emerging therapies and nursing roles.

PMID- 23123816
TI  - The secreted protein acidic and rich in cysteine (SPARC) induces endoplasmic
      reticulum stress leading to autophagy-mediated apoptosis in neuroblastoma.
AB  - Our previous studies showed that overexpression of secreted protein acidic and
      rich in cysteine (SPARC) induced autophagy-mediated apoptosis in PNET cells. In
      the present study, we attempted to elucidate the molecular mechanisms and
      signaling cascades associated with SPARC overexpression in combination with
      radiation therapy that eventually leads to autophagy-mediated apoptosis in
      neuroblastoma. SPARC expression in SK-N-AS and NB-1691 cells demonstrated the
      activation of caspase 3, cleavage of PARP and induction of apoptosis. The
      experiments to unravel the mechanisms associated with autophagy-apoptosis
      illustrated that SPARC overexpression triggered endoplasmic reticulum (ER) stress
      and thereby unfolded protein response (UPR). This was apparent with the
      activation of stress receptors, inositol-requiring enzyme (IRE 1alpha), RNA
      dependent protein kinase (PKR)-like ER kinase (PERK) and BiP. This study further
      demonstrated the induction of transcription factor CHOP as a result of IRE-JNK
      activation in response to increased SPARC levels. Inhibition of ER stress and JNK
      activation led to inhibition of autophagy-mediated apoptosis. Further, the
      apparent expression of ER stress molecules among the orthotopic tumors treated by
      SPARC overexpression plasmids substantiated our in vitro observations. Taken
      together, these results illustrate the critical role of ER stress in regulating
      autophagy-mediated apoptosis in SPARC-overexpressed neuroblastoma cells and
      radiation treatment.

PMID- 23123817
TI  - Muscle protein kinetics in cancer cachexia.
AB  - PURPOSE OF REVIEW: Skeletal muscle loss appears to be the most significant event
      in cancer cachexia and is associated with a poor outcome. The balance between
      mechanisms that control synthesis and degradation is fundamental when designing
      new therapies. This review aims to highlight the molecular mechanisms that are
      associated with protein kinetics. RECENT FINDINGS: The mechanisms that promote
      muscle synthesis have been explored in detail recently but moreover they have
      been the mechanisms behind degradation. Specific advances in cellular signalling
      molecules related to autophagy pathways including signal transducer and
      activators of transcription-3, activin type-2 receptor, TRAF6, and transcriptomic
      research have been given special attention in this review to highlight their
      roles in degradation and as potential targets for therapeutics. Ways to quantify
      muscle loss are badly needed for outcome measures; recent research using
      radiolabelled amino acids has also been discussed in this review. SUMMARY: Only
      by having an appreciation of the complex regulation of muscle protein synthesis
      and degradation, will potential new therapeutics be able to be developed. This
      review identifies known targets in molecular pathways of current interest,
      explores methods used to find novel genes which may be involved in muscle
      kinetics and also highlights ways in which muscle kinetics may be measured to
      assess the efficacy of such interventions.

PMID- 23123818
TI  - Translational implications of novel findings in cancer cachexia:  the use of
      metabolomics and the potential of cardiac malfunction.
AB  - PURPOSE OF REVIEW: Cancer cachexia is a complex metabolic syndrome that manifests
      as a progressive wasting disorder. Recent findings have substantially improved
      our understanding of this unique entity shedding light on a potentially
      significant and overlooked morbidity in the form of cardiac functional changes
      that may occur in tandem with cachexia. Moreover, recent technological advances,
      such as with the application of metabolomic analysis, have yielded a better
      understanding of the metabolic changes that accompany this condition. RECENT
      FINDINGS: Recent evidence from murine studies indicates that the skeletal muscle
      wasting in cancer cachexia may be accompanied by cardiac muscle wasting. This
      decreased heart weight is accompanied by functional cardiac changes, which are
      suggestive of congestive heart failure. In addition, metabolomic analysis of body
      fluids and tissues distinguishes cancer cachexia's unique metabolic fingerprint
      as a separate entity, different from healthy controls, tumor burden, caloric
      restriction, and aging. It also gives insight into the metabolic changes that
      occur in the affected tissues such as the Warburg effect that is not often
      described in muscle. SUMMARY: Translational investigations into potential cardiac
      malfunction in cancer patients and metabolomic analyses of patients' sera and
      tissues are warranted to determine whether these changes are upheld in humans.

PMID- 23123819
TI  - Editorial:  death to the fiefdoms.

PMID- 23123820
TI  - Topics in research:  structuring studies in palliative care.
AB  - PURPOSE OF REVIEW: This review describes the advances in trial methodology and
      presents new methodologies to meet some of the challenges of conducting trials in
      a palliative care setting. To describe why this review is timely and relevant.
      RECENT FINDINGS: This review discusses the process required to conduct trials of
      complex interventions described by the Britain's Medical Research Council. It
      discusses the importance of feasibility trials and the quantitative research
      inherent in these trials. It describes the design alternatives to the classic
      randomized controlled trials (RCTs), including cluster randomization, step wedge
      and fast-track randomization, and n-of-1 trial design. The strengths and
      weaknesses of each are described. SUMMARY: An understanding of the limitations of
      RCTs is important. It is important that clinicians and researchers understand the
      need for alternative trial design and how and when to use them.

PMID- 23123815
TI  - Mitochondrial glutathione: features, regulation and role in disease.
AB  - BACKGROUND: Mitochondria are the powerhouse of mammalian cells and the main
      source of reactive oxygen species (ROS) associated with oxygen consumption. In
      addition, they also play a strategic role in controlling the fate of cells
      through regulation of death pathways. Mitochondrial ROS production fulfills a
      signaling role through regulation of redox pathways, but also contributes to
      mitochondrial damage in a number of pathological states. SCOPE OF REVIEW:
      Mitochondria are exposed to the constant generation of oxidant species, and yet
      the organelle remains functional due to the existence of an armamentarium of
      antioxidant defense systems aimed to repair oxidative damage, of which
      mitochondrial glutathione (mGSH) is of particular relevance. Thus, the aim of the
      review is to cover the regulation of mGSH and its role in disease. MAJOR
      CONCLUSIONS: Cumulating evidence over recent years has demonstrated the essential
      role for mGSH in mitochondrial physiology and disease. Despite its high
      concentration in the mitochondrial matrix, mitochondria lack the enzymes to
      synthesize GSH de novo, so that mGSH originates from cytosolic GSH via transport
      through specific mitochondrial carriers, which exhibit sensitivity to membrane
      dynamics. Depletion of mGSH sensitizes cells to stimuli leading to oxidative
      stress such as TNF, hypoxia or amyloid beta-peptide, thereby contributing to
      disease pathogenesis. GENERAL SIGNIFICANCE: Understanding the regulation of mGSH
      may provide novel insights to disease pathogenesis and toxicity and the
      opportunity to design therapeutic targets of intervention in cell death
      susceptibility and disease. This article is part of a Special Issue entitled
      Cellular functions of glutathione.

PMID- 23123821
TI  - Current world literature.

PMID- 23123823
TI  - Evaluation of transcervical insemination using frozen semen by flexible endoscope
      in dogs.
AB  - We evaluated transcervical insemination (TCI) using frozen semen by flexible
      endoscopy in dogs. Eight female and eight male beagles were used in this study. A
      flexible endoscope and a washing tube were used for TCI. A tracheal tube was used
      as an alternative to the penis and was an auxiliary for inserting the flexible
      endoscope. The mean time required to insert the washing tube into the external os
      of the uterus after inserting the endoscope into the tracheal tube was 7.5 min.
      Slight or mild pain was observed in all bitches during TCI. However, TCI could be
      easily performed with retention in all bitches and without sedation anesthesia.
      The tracheal tube was useful to ensure the visual field using air sufflation.
      Clinical signs suspicious of infection were not observed in any bitches from the
      TCI to the pregnancy diagnosis. The conception rate was 87.5%, and the mean
      number of fetuses was 6.3. TCI using a flexible endoscope in bitches was
      performed quickly with minimal invasiveness. We present a new method of TCI in
      dogs. This method should be studied in small and large breeds to obtain more
      detailed results.

PMID- 23123824
TI  - Molecular identification of avian haemosporidia in wild birds and mosquitoes on
      Tsushima Island, Japan.
AB  - We investigated for the first time the prevalence of avian haemosporidia of
      genera Plasmodium, Haemoproteus and Leucocytozoon among birds and mosquitoes on
      Tsushima Island of Japan, which is located between Japan and the Korean
      Peninsula. Of 55 wild birds belonging to 33 species, 16 (29.1%) tested positive
      for haemosporidia as follows: Plasmodium spp. (11/55; 20.0%); Haemoproteus spp.
      (2/55; 3.6%); and Leucocytozoon spp. (3/55; 5.5%). A genetic lineage isolated
      from the Eurasian Sparrowhawk (Accipiter nisus) was identical to that of the
      known avian malaria parasite P. circumflexum. Several genetic lineages were
      identical or closely related to the parasite lineages that were previously
      detected in birds and mosquitoes in Japan and Korea. Another single identical
      genetic lineage was also detected in both migratory and resident birds. A total
      of 753 mosquitoes from 12 species were collected; and one fully fed Aedes
      albopictus was positive for avian Plasmodium(1/753; 0.13%) which is identical to
      a genetic lineage detected in both mosquitoes in Japan and birds in Korea. Blood
      meal identifications of blood-fed mosquitoes showed direct contact between the
      mosquitoes and 4 species of mammals including humans, cattle, rodents and the
      endangered Tsushima leopard cat (Prionailurus bengalensis euptilura). Migratory
      birds use Tsushima Island as a site for wintering, breeding and resting, and our
      results suggest the transmission of avian haematozoa between resident and
      migratory birds during their stay on Tsushima Island.

PMID- 23123825
TI  - Genetic and antigenic characterization of Indian foot-and-mouth disease virus
      serotype O isolates collected during the period 2001 to 2012.
AB  - The phylogenetic analysis of VP1 sequences of the 39 type O foot and mouth virus
      (FMDV) isolates collected from different regions of India during the year of 2001
      12 revealed that all isolates belonged to the Middle East - South Asia (ME-SA)
      topotype. Based on the amount of divergence among the isolates, the viruses were
      further classified into three distinct lineages namely Ind 2001, PanAsia and
      PanAsia-2 as well as a minor, unnamed group. Ind 2001 lineage viruses accounted
      for most of the current type O outbreaks. At the nucleotide level these isolates
      showed a divergence of 2% to 14% with an average sequence variation of ~9.9%. The
      serological spectrum of the current vaccine strain was studied by using bovine
      vaccinate serum (BVS) raised against O/IND/R2/75. All the current field isolates
      (n=24) were homologous ('r' value 0.4 to 1.0) to the vaccine strain. Examination
      of the amino acid sequences for selection pressure revealed the positive
      selection at amino acid sites 13 and 45.

PMID- 23123826
TI  - A multi-plane source model for out-of-field head scatter dose calculations in
      external beam photon therapy.
AB  - Our purpose was to assess the out-of-field dose component related to head scatter
      radiation in high-energy photon therapy beams and then derive a multisource model
      for this dose component. For scattered photons, several planar sources have been
      defined, with number, location and tilt depending on the complexity of the field
      shape. In the absence of precise knowledge of out-of-field scattering
      characteristics, several assumptions are made to derive emission spectra and
      radiation intensity from measurements. Among these, the Compton formula is used
      to evaluate scattered photon energy and the Henyey-Greenstein phase function is
      used to evaluate the scattered photon angular distribution. For measured doses
      under out-of-field conditions, the average local difference between the
      calculated and measured photon dose is 10%, including doses as low as 0.01% of
      the maximum dose on the beam axis. This study demonstrates that the multi-plane
      source approach is suitable for accurate analytical modeling of the out-of-field
      dose component related to head scatter radiation. These results should be taken
      into account when evaluating doses to the remaining volume at risk in external
      beam radiotherapy planning.

PMID- 23123828
TI  - Preanalytical evaluation of serum 25-hydroxyvitamin D3 and 25-hydroxyvitamin D2
      measurements using LC-MS/MS.
AB  - BACKGROUND: Vitamin D testing is increasing worldwide. Although immunoassays are
      still widely used in Japan for the measurement of serum 25-hydroxyvitamin D
      (25OHD) as an indicator of vitamin D status, development of a simple and high
      throughput MS-based method is still needed for routine use in clinical
      laboratories. METHODS: We designed a method using a triple quadrupole mass
      spectrometer equipped with a two-step separation approach that used the Aria TLX
      2 HPLC system in the selected reaction monitoring mode. Analytical performance of
      the system and effects of various preanalytical factors were tested. RESULTS:
      High-throughput quantitative analysis of 25OHD3 and D2 at 15 samples/h was
      achieved using 25 MUl of serum/plasma. Intra- and inter-assay CVs for 25OHD3 were
      5% and 7%, respectively. Limit of detection for 25OHD3 was 0.31 ng/ml. No
      significant effects were seen for clotting time, repeated freeze-thaw cycles,
      anti-coagulants and possible interfering substances. A good correlation
      (r(2)=0.947) was found between the present system and the DiaSorin
      radioimmunoassay. Serum 25OHD3 levels in apparently healthy Japanese subjects
      were 25.5+/-9.8 ng/ml for men and 20.9+/-7.1 ng/ml for women. CONCLUSIONS: This
      high-throughput LC-MS/MS 25-OHD assay has the potential to be used as a routine
      clinical laboratory assay for assessing vitamin D status.

PMID- 23123829
TI  - Quantification of citrulline by parallel fragmentation monitoring--a novel method
      using graphitized carbon nanoparticles and MALDI-TOF/TOF mass spectrometry.
AB  - BACKGROUND: Selected reaction monitoring (SRM) is a reliable mass spectrometry
      (MS)-based technique for quantification of small molecules. However, it is not
      applicable to matrix-assisted laser desorption/ionization time-of-flight/time-of
      flight tandem MS (MALDI-TOF/TOF MS) instruments. This work presents a novel
      comparable MALDI-TOF/TOF MS technique, "Parallel Fragmentation Monitoring" (PFM),
      for high-throughput quantification of citrulline. METHOD: Calibrator/sample
      solutions were spiked with internal standard that was a stable isotopic analog
      with 1 mass unit heavier than citrulline. Both citrulline and internal standard
      were isolated and fragmented in parallel by MALDI-TOF/TOF MS in the presence of
      graphitized carbon nanoparticles as matrix. The ratio of the peak intensities of
      the selected fragment of citrulline to that of internal standard was used to
      calibrate/calculate the concentrations of citrulline in samples. RESULTS: Linear
      calibration curves were obtained in the range of 10-250 MUmol/l citrulline with
      correlation coefficients >=0.997. Stored calibration curve and batch-specific
      calibration curve produced highly similar measurement values. Within- and between
      day CVs were 3.1-8.7% and 3.5-10.6%, respectively, illustrating the reliability
      and robustness of PFM. CONCLUSION: Using citrulline for proof-of-concept, we have
      developed the PFM technique with tremendous potential for high-throughput
      quantification of amino acids and other small molecules.

PMID- 23123827
TI  - Review of S100A9 biology and its role in cancer.
AB  - S100A9 is a calcium binding protein with multiple ligands and post-translation
      modifications that is involved in inflammatory events and the initial development
      of the cancer cell through to the development of metastatic disease. This review
      has a threefold purpose: 1) describe the S100A9 structural elements important for
      its biological activity, 2) describe the S100A9 biology in the context of the
      immune system, and 3) illustrate the role of S100A9 in the development of
      malignancy via interactions with the immune system and other cellular processes.

PMID- 23123831
TI  - Bacterial profile from caecal contents and soft faeces in growing rabbits given
      diets differing in soluble and insoluble fibre levels.
AB  - To verify if non-invasive collection of soft faeces (SF) from rabbits can be used
      as an index of bacterial biodiversity in caecal contents (CC), 24 weaned rabbits
      were given diets with low (LI) and high (HI) levels of insoluble fibre (neutral
      detergent fibre, NDF) and low (LS) and high (HS) levels of soluble fibre (neutral
      detergent soluble fibre, NDSF). After 21 days, animals were fitted with neck
      collars for SF collection. Two days later, animals were slaughtered and CC
      sampled. Total bacterial concentration quantified by real time PCR (log(10) ng
      DNA/mg DM) was higher in SF than CC (2.615 vs. 2.383). Among diets, in CC it was
      (P = 0.059) lowest in LILS diet, whereas in SF it decreased (P = 0.025) with the
      NDF level. DGGE profiles showed that structure of bacterial communities of SF was
      close to that of CC; however, similarity was higher in LI than HI diets (0.82 vs.
      0.74). Diversity indexes in CC decreased with NDSF (P < 0.05), whereas the effect
      of NDF (P < 0.05) was also appreciated in SF. Soft faeces can be an alternative
      to surgery or slaughter techniques to monitor changes in caecal bacterial
      community; however, high dietary NDF may decrease similarity between both
      communities.

PMID- 23123830
TI  - Association of vaspin gene polymorphisms with coronary artery disease in Chinese
      population and function study.
AB  - BACKGROUND: Visceral adipose tissue-derived serine protease inhibitor (vaspin) is
      a recently identified adipokine. Studies suggest it is involved in many diseases
      such as obesity, diabetes and coronary artery disease (CAD). This study is to
      investigate the association of single nucleotide polymorphisms (SNPs) in vaspin
      with CAD and its potential mechanisms. METHODS: A total of 1570 consecutive
      patients undergoing coronary angiography were enrolled and the genotypes were
      determined by TaqMan allelic discrimination. Serum vaspin concentrations and mRNA
      expression levels were determined by ELISA and RT-PCR, respectively. Reporter
      gene assay was performed to investigate the effect of polymorphism on vaspin
      promoter function. RESULTS: After multivariate analysis, allele A of rs2236242
      was found as an independent determinant of CAD (OR=1.32, p=0.004). Rs35262691 in
      vaspin promoter was associated with serum vaspin concentration and mRNA
      expression in peripheral blood mononuclear cells (PBMC) though no association had
      been found with CAD. Reporter gene assay further confirmed that CC genotype of
      rs35262691 had 2.1+/-0.4-fold higher activities than TT genotype in facilitating
      gene expression. CONCLUSIONS: Our results show that the variants of vaspin gene
      are associated with serum vaspin levels and risk for CAD in Chinese population.

PMID- 23123832
TI  - The antimicrobial effects of deglycyrrhizinated licorice root extract on
      Streptococcus mutans UA159 in both planktonic and biofilm cultures.
AB  - The objective of the study was to investigate the antimicrobial effects of
      deglycyrrhizinated licorice root extracts (DG-LRE) against Streptococcus mutans
      UA159 in both the planktonic and biofilm phases by determining the minimum
      inhibitory concentration and minimum bactericidal concentration, and by
      performing time-kill kinetic, growth, adhesion, and biofilm assays. The cell
      toxicity of DG-LRE on normal human gingival fibroblast (NHGF) cells was tested
      using a methyl thiazolyl tetrazolium assay. This study showed that DG-LRE had
      strong antimicrobial activity against S. mutans in the planktonic phase with
      little cytotoxic effect on NHGF cells. In addition, DG-LRE significantly
      inhibited biofilm formation by S. mutans UA159 at concentrations over 4 MUg/ml
      for glucose or 16 MUg/ml for sucrose, respectively, regardless of the presence of
      saliva-coating. To the best of our knowledge, this is the first report to provide
      evidence that DG-LRE demonstrates antimicrobial activity against S. mutans. These
      results suggest that DG-LRE can be used in developing oral hygiene products, such
      as gargling solution and dentifrice to prevent human dental caries.

PMID- 23123833
TI  - Micromotor-based lab-on-chip immunoassays.
AB  - Here we describe the first example of using self-propelled antibody
      functionalized synthetic catalytic microengines for capturing and transporting
      target proteins between the different reservoirs of a lab-on-a-chip (LOC) device.
      A new catalytic polymer/Ni/Pt microtube engine, containing carboxy moieties on
      its mixed poly(3,4-ethylenedioxythiophene) (PEDOT)/COOH-PEDOT polymeric outermost
      layer, is further functionalized with the antibody receptor to selectively
      recognize and capture the target protein. The new motor-based microchip
      immunoassay operations are carried out without any bulk fluid flow, replacing the
      common washing steps in antibody-based protein bioassays with the active
      transport of the captured protein throughout the different reservoirs, where each
      step of the immunoassay takes place. A first microchip format involving an 'on
      the-fly' double-antibody sandwich assay (DASA) is used for demonstrating the
      selective capture of the target protein, in the presence of excess of non-target
      proteins. A secondary antibody tagged with a polymeric-sphere tracer allows the
      direct visualization of the binding events. In a second approach the immuno
      nanomotor captures and transports the microsphere-tagged antigen through a
      microchannel network. An anti-protein-A modified microengine is finally used to
      demonstrate the selective capture, transport and convenient label-free optical
      detection of a Staphylococcus aureus target bacteria (containing proteinA in its
      cell wall) in the presence of a large excess of non-target (Saccharomyces
      cerevisiae) cells. The resulting nanomotor-based microchip immunoassay offers
      considerable potential for diverse applications in clinical diagnostics,
      environmental and security monitoring fields.

PMID- 23123834
TI  - Clicked europium dipicolinate complexes for protein X-ray structure
      determination.
AB  - New trisdipicolinic acid-lanthanide complexes are reported as phasing agents for
      X-ray crystallography of proteins. It is demonstrated that CuAAC modifications
      allow protein co-crystallization with low concentration of lanthanide complexes
      leading to an accurate structure determination.

PMID- 23123835
TI  - Health visiting services and the Government's pledge.

PMID- 23123836
TI  - Erasmus over 25 years - and a Swedish experience.

PMID- 23123837
TI  - Recent developments in enteral feeding for adults: an update.
AB  - In the 1980s, enteral nutrition became increasingly recognised as a safe,
      effective and cost-efficient method of providing nutrition to patients with a
      functional gut (Silk, 2003). With this came the development of feeding-specific
      nasogastric (NG) tubes (Rees et al, 1986) and the formulation of nutritionally
      complete, ready-to-hang feeds (Keohane et al, 1983), as well as the creation of
      gastrostomy tubes for direct access to the stomach by Ponsky and Gauderer (1981)
      followed by jejunostomys 11 years later (Shike et al, 1991). Since then there
      have been many developments in every aspect of enteral feeding, with over 30
      enteral feeds listed in the British National Formulary (BNF) (Joint Formulary
      Committee, 2012) and companies continually designing new tubes that are smaller
      or more comfortable and feeding pumps that are quieter and easier to use. This
      article discusses the developments in enteral feeding over the last 5 years to
      give the reader an update on current topics and issues in enteral feeding.

PMID- 23123838
TI  - Infection control in enteral feed and feeding systems in the community.
AB  - This article examines the infection risk to adult patients receiving home enteral
      nutrition (HEN) and strategies for its prevention and management. Enteral
      nutrition was historically associated with acute care settings owing to its
      invasive nature. The changing landscape of community care means that it is now
      likely to be administered in the patient's home or in other community settings
      such as nursing homes. HEN is associated with two main routes of infection risks:
      the risk of gastrointestinal infection from contamination of the feed and feeding
      accessories, and local wound infection at the stoma site. Guidelines for the
      prevention and control of HEN-associated infection are provided and explained.
      These guidelines emphasise patient and carer education, effective hand hygiene,
      correct storage and administration of the feed, early detection and management of
      potential infections.

PMID- 23123839
TI  - Developing a clinical academic career pathway for nursing.
AB  - Since the publication of the UK Clinical Research Collaboration's (UKRC, 2007)
      recommendations on careers in clinical research, interest has grown in the
      concept of clinical academic nursing careers, with increased debate on how such
      roles might be developed and sustained (Department of Health, 2012). To embed
      clinical academic nursing roles in the NHS and universities, a clear
      understanding and appreciation of the contribution that such posts might make to
      organisational objectives and outcomes must be developed. This paper outlines an
      initiative to define the potential practice and research contribution of clinical
      academic roles through setting out role descriptors. This exercise was based on
      our experience of a clinical academic career initiative at the University of
      Southampton run in partnership with NHS organisations. Role descriptors were
      developed by a group of service providers, academics and two clinical academic
      award-holders from the local programme. This paper outlines clinical academic
      roles from novice to professor and describes examples of role descriptors at the
      different levels of a career pathway. These descriptors are informed by clinical
      academic posts in place at Southampton as well as others at the planning stage.
      Understanding the nature of clinical academic posts and the contribution that
      these roles can make to healthcare will enable them to become embedded into
      organisational structures and career pathways.

PMID- 23123841
TI  - Proxemic communication between HIV-infected mother-child pairs.
AB  - Proxemic communication (behaviours and relations of human interaction) offered by
      the mother in an HIV-infected mother-child pair during infancy was analysed to
      determine which proxemic factors promote the exchange of affection. This study,
      conducted in an experimental laboratory in 2007, included mother-child pairs in
      which the mother was HIV-positive and the children, under 6 months of age, were
      born exposed to the virus. Video recordings of the mother-child interaction were
      analysed according to proxemic factors. Of the 364 interactions recorded for
      analysis of proxemic communication between the mother-child pair, the most
      significant proxemic factors were axis, contact behavior, visual code, and tone
      of voice. The mothers developed communicative strategies such as closer
      proximity, touch, vocalisation, and smiling to promote the exchange of affection
      when engaging in maternal care.

PMID- 23123840
TI  - Initiating growth hormone therapy for children and adolescents.
AB  - It is common for children and adolescents on growth hormone (GH) treatment to
      miss one or more injections per week, thereby compromising their linear growth
      outcome. Among factors likely to affect treatment concordance are patient
      education and support in the selection of the most appropriate GH injection
      device. The authors discovered inconsistencies in the process of starting
      patients on GH therapy throughout the UK, and found that there were no clinical
      recommendations to support health professionals starting patients on treatment.
      This article describes the issues involved and the development of practical
      recommendations for use when starting paediatric patients on long-term GH
      therapy.

PMID- 23123842
TI  - Time to repeal the  Tattooing of Minors Act 1969.
AB  - The Health Protection Agency has again issued a warning to teenagers about the
      risks of infection and transmission of bloodborne diseases from using home tattoo
      kits. The warning came after two children from Sussex needed hospital treatment
      for infected tattoos. The trend for teenagers to use kits bought online or to
      have home tattoo parties is becoming a more common way to overcome the legal ban
      on tattooing minors. Richard Griffith argues that the public health risk to
      children from the use of unsterile home tattooing equipment can be countered by
      repealing the law prohibiting the tattooing of minors so that they can be
      protected, as adults are, by a regulated and licensed tattoo industry.

PMID- 23123843
TI  - 'This is Nursing': an initiative to reshape the vision of nursing.

PMID- 23123844
TI  - Identifying defects in the quality  of primary and secondary care.

PMID- 23123845
TI  - Teaching and learning: from staff nurse to nurse consultant. Part 8: mentoring
      students.

PMID- 23123846
TI  - Issues of patient sexuality in nurse education.

PMID- 23123847
TI  - Facing up to the Francis report.

PMID- 23123848
TI  - Superluminous supernovae at redshifts of 2.05 and 3.90.
AB  - A rare class of 'superluminous' supernovae that are about ten or more times more
      luminous at their peaks than other types of luminous supernova has recently been
      found at low to intermediate redshifts. A small subset of these events have
      luminosities that evolve slowly and result in radiated energies of up to about
      10(51) ergs. Therefore, they are probably examples of 'pair-instability' or
      'pulsational pair-instability' supernovae with estimated progenitor masses of 100
      to 250 times that of the Sun. These events are exceedingly rare at low redshift,
      but are expected to be more common at high redshift because the mass distribution
      of the earliest stars was probably skewed to high values. Here we report the
      detection of two superluminous supernovae, at redshifts of 2.05 and 3.90, that
      have slowly evolving light curves. We estimate the rate of events at redshifts of
      2 and 4 to be approximately ten times higher than the rate at low redshift. The
      extreme luminosities of superluminous supernovae extend the redshift limit for
      supernova detection using present technology, previously 2.36 (ref. 8), and
      provide a way of investigating the deaths of the first generation of stars to
      form after the Big Bang.

PMID- 23123850
TI  - Astrophysics: Cosmic explosions in the young Universe.

PMID- 23123849
TI  - Structure of the Mediator head module.
AB  - Gene transcription by RNA polymerase (Pol) II requires the coactivator complex
      Mediator. Mediator connects transcriptional regulators and Pol II, and is linked
      to human disease. Mediator from the yeast Saccharomyces cerevisiae has a
      molecular mass of 1.4 megadaltons and comprises 25 subunits that form the head,
      middle, tail and kinase modules. The head module constitutes one-half of the
      essential Mediator core, and comprises the conserved subunits Med6, Med8, Med11,
      Med17, Med18, Med20 and Med22. Recent X-ray analysis of the S. cerevisiae head
      module at 4.3 A resolution led to a partial architectural model with three
      submodules called neck, fixed jaw and moveable jaw. Here we determine de novo the
      crystal structure of the head module from the fission yeast Schizosaccharomyces
      pombe at 3.4 A resolution. Structure solution was enabled by new structures of
      Med6 and the fixed jaw, and previous structures of the moveable jaw and part of
      the neck, and required deletion of Med20. The S. pombe head module resembles the
      head of a crocodile with eight distinct elements, of which at least four are
      mobile. The fixed jaw comprises tooth and nose domains, whereas the neck
      submodule contains a helical spine and one limb, with shoulder, arm and finger
      elements. The arm and the essential shoulder contact other parts of Mediator. The
      jaws and a central joint are implicated in interactions with Pol II and its
      carboxy-terminal domain, and the joint is required for transcription in vitro.
      The S. pombe head module structure leads to a revised model of the S. cerevisiae
      module, reveals a high conservation and flexibility, explains known mutations,
      and provides the basis for unravelling a central mechanism of gene regulation.

PMID- 23123853
TI  - Cancer: Complexion matters.

PMID- 23123854
TI  - An ultraviolet-radiation-independent pathway to melanoma carcinogenesis in the
      red hair/fair skin background.
AB  - People with pale skin, red hair, freckles and an inability to tan--the 'red
      hair/fair skin' phenotype--are at highest risk of developing melanoma, compared
      to all other pigmentation types. Genetically, this phenotype is frequently the
      product of inactivating polymorphisms in the melanocortin 1 receptor (MC1R) gene.
      MC1R encodes a cyclic AMP-stimulating G-protein-coupled receptor that controls
      pigment production. Minimal receptor activity, as in red hair/fair skin
      polymorphisms, produces the red/yellow pheomelanin pigment, whereas increasing
      MC1R activity stimulates the production of black/brown eumelanin. Pheomelanin has
      weak shielding capacity against ultraviolet radiation relative to eumelanin, and
      has been shown to amplify ultraviolet-A-induced reactive oxygen species. Several
      observations, however, complicate the assumption that melanoma risk is completely
      ultraviolet-radiation-dependent. For example, unlike non-melanoma skin cancers,
      melanoma is not restricted to sun-exposed skin and ultraviolet radiation
      signature mutations are infrequently oncogenic drivers. Although linkage of
      melanoma risk to ultraviolet radiation exposure is beyond doubt, ultraviolet
      radiation-independent events are likely to have a significant role. Here we
      introduce a conditional, melanocyte-targeted allele of the most common melanoma
      oncoprotein, BRAF(V600E), into mice carrying an inactivating mutation in the Mc1r
      gene (these mice have a phenotype analogous to red hair/fair skin humans). We
      observed a high incidence of invasive melanomas without providing additional gene
      aberrations or ultraviolet radiation exposure. To investigate the mechanism of
      ultraviolet-radiation-independent carcinogenesis, we introduced an albino allele,
      which ablates all pigment production on the Mc1r(e/e) background. Selective
      absence of pheomelanin synthesis was protective against melanoma development. In
      addition, normal Mc1r(e/e) mouse skin was found to have significantly greater
      oxidative DNA and lipid damage than albino-Mc1r(e/e) mouse skin. These data
      suggest that the pheomelanin pigment pathway produces ultraviolet-radiation
      independent carcinogenic contributions to melanomagenesis by a mechanism of
      oxidative damage. Although protection from ultraviolet radiation remains
      important, additional strategies may be required for optimal melanoma prevention.

PMID- 23123855
TI  - Vascular biology: Nitric oxide caught in traffic.

PMID- 23123856
TI  - Evolutionary biology: Birds of a feather.

PMID- 23123857
TI  - The global diversity of birds in space and time.
AB  - Current global patterns of biodiversity result from processes that operate over
      both space and time and thus require an integrated macroecological and
      macroevolutionary perspective. Molecular time trees have advanced our
      understanding of the tempo and mode of diversification and have identified
      remarkable adaptive radiations across the tree of life. However, incomplete joint
      phylogenetic and geographic sampling has limited broad-scale inference. Thus, the
      relative prevalence of rapid radiations and the importance of their geographic
      settings in shaping global biodiversity patterns remain unclear. Here we present,
      analyse and map the first complete dated phylogeny of all 9,993 extant species of
      birds, a widely studied group showing many unique adaptations. We find that birds
      have undergone a strong increase in diversification rate from about 50 million
      years ago to the near present. This acceleration is due to a number of
      significant rate increases, both within songbirds and within other young and
      mostly temperate radiations including the waterfowl, gulls and woodpeckers.
      Importantly, species characterized with very high past diversification rates are
      interspersed throughout the avian tree and across geographic space.
      Geographically, the major differences in diversification rates are hemispheric
      rather than latitudinal, with bird assemblages in Asia, North America and
      southern South America containing a disproportionate number of species from
      recent rapid radiations. The contribution of rapidly radiating lineages to both
      temporal diversification dynamics and spatial distributions of species diversity
      illustrates the benefits of an inclusive geographical and taxonomical
      perspective. Overall, whereas constituent clades may exhibit slowdowns, the
      adaptive zone into which modern birds have diversified since the Cretaceous may
      still offer opportunities for diversification.

PMID- 23123859
TI  - Planning prompts as a means of increasing preventive screening rates.

PMID- 23123858
TI  - Endothelial cell expression of haemoglobin alpha regulates nitric oxide
      signalling.
AB  - Models of unregulated nitric oxide (NO) diffusion do not consistently account for
      the biochemistry of NO synthase (NOS)-dependent signalling in many cell systems.
      For example, endothelial NOS controls blood pressure, blood flow and oxygen
      delivery through its effect on vascular smooth muscle tone, but the regulation of
      these processes is not adequately explained by simple NO diffusion from
      endothelium to smooth muscle. Here we report a new model for the regulation of NO
      signalling by demonstrating that haemoglobin (Hb) alpha (encoded by the HBA1 and
      HBA2 genes in humans) is expressed in human and mouse arterial endothelial cells
      and enriched at the myoendothelial junction, where it regulates the effects of NO
      on vascular reactivity. Notably, this function is unique to Hb alpha and is
      abrogated by its genetic depletion. Mechanistically, endothelial Hb alpha haem
      iron in the Fe(3+) state permits NO signalling, and this signalling is shut off
      when Hb alpha is reduced to the Fe(2+) state by endothelial cytochrome b5
      reductase 3 (CYB5R3, also known as diaphorase 1). Genetic and pharmacological
      inhibition of CYB5R3 increases NO bioactivity in small arteries. These data
      reveal a new mechanism by which the regulation of the intracellular Hb alpha
      oxidation state controls NOS signalling in non-erythroid cells. This model may be
      relevant to haem-containing globins in a broad range of NOS-containing somatic
      cells.

PMID- 23123860
TI  - Clustering of risk behaviors for chronic noncommunicable diseases: a population
      based study in southern Brazil.
AB  - OBJECTIVE: The purpose of this study was to investigate the prevalence and
      identify factors associated with simultaneous risk behaviors for chronic
      noncommunicable diseases in adults in a southern capital in Brazil. METHOD: A
      cross-sectional, population-based study was carried out with 1720 adults in
      Florianopolis, Brazil. The simultaneous occurrence of tobacco smoking, abusive
      drinking, inadequate or unhealthy diet, and physical inactivity during leisure
      was assessed. The independent variables were demographic and socioeconomic
      characteristics. RESULTS: Only 8.3% of the respondents did not have any of these
      factors, whereas the simultaneous occurrence of two or more risk behaviors was
      59.4%. The simultaneous presence of four risk behaviors (3.4%) was 220% higher of
      what would be expected by combining the individual prevalence of these factors
      (1.5%). The likelihood of individuals having two or more risk behaviors
      simultaneously was greater in young men, with black skin color, living without a
      partner, with lower household per capita income, and lower education. CONCLUSION:
      It is necessary to implement programs that reduce the risk behaviors for chronic
      noncommunicable diseases among adults in Brazil, especially between young men
      with low education and income.

PMID- 23123861
TI  - Creating a healthy milieu for all. Essay on the current state and future of
      preventive medicine.

PMID- 23123862
TI  - Psychiatric comorbidity and causal disease models.
AB  - In psychiatry, comorbidity is the rule rather than the exception. Up to 45% of
      all patients are classified as having more than one psychiatric disorder. These
      high rates of comorbidity have led to a debate concerning the interpretation of
      this phenomenon. Some authors emphasize the problematic character of the high
      rates of comorbidity because they indicate absent zones of rarities. Others
      consider comorbid conditions to be a validator for a particular reclassification
      of diseases. In this paper we will show that those at first sight contrasting
      interpretations of comorbidity are based on similar assumptions about disease
      models. The underlying ideas are that firstly high rates of comorbidity are the
      result of the absence of causally defined diseases in psychiatry, and second that
      causal disease models are preferable to non-causal disease models. We will argue
      that there are good reasons to seek after causal understanding of psychiatric
      disorders, but that causal disease models will not rule out high rates of
      comorbidity--neither in psychiatry, nor in medicine in general. By bringing to
      the fore these underlying assumptions, we hope to clear the ground for a
      different understanding of comorbidity, and of models for psychiatric diseases.

PMID- 23123864
TI  - The expanding universe of mitochondrial research.

PMID- 23123863
TI  - Big 5 personality traits and interleukin-6: evidence for "healthy Neuroticism" in
      a US population sample.
AB  - The current study investigated if the Big 5 personality traits predicted
      interleukin-6 (IL-6) levels in a national sample over the course of 5years. In
      addition, interactions among the Big 5 were tested to provide a more accurate
      understanding of how personality traits may influence an inflammatory biomarker.
      Data included 1054 participants in the Midlife Development in the U.S. (MIDUS)
      biomarkers subproject. The Big 5 personality traits were assessed in 2005-2006 as
      part of the main MIDUS survey. Medication use, comorbid conditions, smoking
      behavior, alcohol use, body mass index, and serum levels of IL-6 were assessed in
      2005-2009 as part of the biomarkers subproject. Linear regression analyses
      examined personality associations with IL-6. A significant
      Conscientiousness*Neuroticism interaction revealed that those high in both
      Conscientiousness and Neuroticism had lower circulating IL-6 levels than people
      with all other configurations of Conscientiousness and Neuroticism. Adjustment
      for health behaviors diminished the magnitude of this association but did not
      eliminate it, suggesting that lower comorbid conditions and obesity may partly
      explain the lower inflammation of those high in both Conscientiousness and
      Neuroticism. Our findings suggest, consistent with prior speculation, that
      average to higher levels of Neuroticism can in some cases be associated with
      health benefits - in this case when it is accompanied by high Conscientiousness.
      Using personality to identify those at risk may lead to greater personalization
      in the prevention and remediation of chronic inflammation.

PMID- 23123865
TI  - Heat dissipation at a graphene-substrate interface.
AB  - The development of nanoelectronics faces severe challenges from Joule heating,
      leading to high power density and spatial localization of heat, which nucleates
      thermal hot spots, limits the maximum current density and potentially causes
      catastrophic materials failure. Weak interfacial coupling with the substrate is a
      major route for effective heat mitigation in low-dimensional materials such as
      graphene and carbon nanotubes. Here we investigate the molecular-scale physics of
      this process by performing molecular dynamics simulations, and find that
      significant heating in graphene supported by a silicon carbide substrate cannot
      be avoided when the areal power density exceeds P(G) = 0.5 GW m(-2). A steady
      state will be established within 200 ps with a significant temperature difference
      built up across the interface, and the interfacial thermal conductivity kappa(c)
      increases at higher power densities from 10 to 50 MW m(-2) K(-1). These
      observations are explained by a two-resistor model, where strong phonon
      scattering at the interface may perturb the ballistic heat transport and lead to
      a diffusive mechanism. Nanoengineering the interfacial thermal coupling by
      intercalating guest atoms shows potential for designing thermally transparent but
      electronically insulating interfaces, which paves the way for simultaneously
      optimizing thermal management and charge carrier mobility in nanoelectronics.

PMID- 23123866
TI  - Understanding the mechanisms behind deficits in imitation: do individuals with
      autism know 'what' to imitate and do they know 'how' to imitate?
AB  - Although imitation problems have been associated with autism for many years, the
      underlying mechanisms of these problems remain subject to debate. In this
      article, the question whether imitation problems are caused by selection or
      correspondence problems is explored and discussed. This review revealed that
      hypotheses on the nature of imitation problems in autism are complicated and
      inconclusive at the present time. There is some evidence for impaired selection,
      especially implicating poor preferential attention to biological motion and poor
      ascription of intention to action. There is also some evidence that both
      transformations of perspectives and mapping of visual to motor information are
      impaired, characterized as correspondence problems. However, it is not yet clear
      how poor selection processes contribute to correspondence problems and vice
      versa. Insight in this interaction may provide a valuable contribution to our
      understanding of imitation problems in autism. For further research we recommend
      that tasks should be constrained to target as few mechanisms as possible in given
      experiments.

PMID- 23123867
TI  - A brief screening instrument for emotionally unstable and dissocial personality
      disorder in male offenders with intellectual disabilities.
AB  - Personality disorder is prevalent among offenders with intellectual disabilities
      (ID), and it is associated with their risk for violence and recurrent offending
      behaviour. A new staff-rated instrument, the Personality Disorder Characteristics
      Checklist (PDCC), designed to screen for ICD-10 dissocial and emotionally
      unstable personality characteristics was evaluated for its reliability and
      validity, as applied to 129 male forensic patients with ID. Internal consistency
      and test-retest reliability were very good. Supportive evidence for concurrent
      and discriminant validity was obtained in conjunction with an established staff
      rated instrument, but not for patient self-report measures. Construct validity
      support was found for the PDCC in association with violent offence and hospital
      assault history and in significantly accounting for the number of physical
      assaults in hospital, controlling for multiple covariates. Results for the new
      measure were favourable in comparison to established instruments. It clinical
      utility for treatment planning and for the management of risk is discussed.

PMID- 23123868
TI  - Managing lower extremity muscle tone and function in children with cerebral palsy
      via eight-week repetitive passive knee movement intervention.
AB  - This study used a repeated measures design to assess the effect of an eight-week
      repetitive passive movement (RPM) intervention on lower extremity muscle tone and
      function in children with cerebral palsy (CP). Eighteen children (aged 9.5 +/-
      2.1 years) with spastic CP were randomly assigned to a knee RPM intervention
      condition of 3 times a week for 8 weeks or a control condition. The 8 weeks were
      followed by 4 weeks of washout period, after which the participants were crossed
      over to the other group. In the RPM condition, each subject's knees were
      intervened with continuous passive motion device (at a velocity of 15 degrees /s)
      for 20 min. The subjects were evaluated via variables measuring range-of-motion,
      muscle tone, and ambulatory function before, after, 1 day after, and 3 days after
      each intervention. Repeated-measures statistical analyses found significant
      differences between condition variable on active range-of-motion of the knee
      (AROM, increased), relaxation index (RI, increased), Modified Ashworth Scale
      (MAS, decreased), timed up-and-go (TUG, decreased), 6-min walk test (6 MWT,
      increased); and significant differences among time variable including RI, MAS,
      and 6 MWT. No difference was found in passive range-of-motion measurements.
      Repetitive passive movement reduced lower extremity spastic hypertonia in
      children with cerebral palsy, and it also improved ambulatory function in terms
      of walking speed. Effects of this treatment protocol on ambulation lasted up to 3
      days post intervention. Findings of this study provide clinicians and patients an
      alternative, effective and efficient strategy for spastic control and ambulatory
      improvement.

PMID- 23123869
TI  - Predictors of diagnosis of child psychiatric disorder in adult-infant social
      communicative interaction at 12 months.
AB  - To establish which social interactive behaviours predict later psychiatric
      diagnosis, we examined 180 videos of a parent-infant interaction when children
      were aged one year, from within the Avon Longitudinal Study of Parents and
      Children (ALSPAC) cohort. Sixty of the videos involved infants who were later
      diagnosed with a psychiatric disorder at seven years, and 120 were a randomly
      selected sex-matched control group. Interactive behaviours for both the caregiver
      and the one year old infant were coded from the videos according to eight
      holistic categories of interpersonal engagement: Well-being, Contingent
      Responsiveness, Cooperativeness, Involvement, Activity, Playfulness, Fussiness,
      and Speech. Lower levels of adult activity and speech in interaction at one year
      significantly predicted overall diagnosis of child psychiatric disorder.

PMID- 23123870
TI  - The moderating effects of intellectual development on core symptoms of autism and
      PDD-NOS in toddlers and infants.
AB  - Little research has been conducted on whether deficits in developmental
      functioning affect the range of core symptoms for autism spectrum disorders
      (ASD). This study represents a first attempt to determine whether developmental
      level has an effect on the expression of ASD symptoms in infants and toddlers.
      Eight hundred and fifty-three infants were evaluated with respect to the nature
      and extent of their ASD symptoms and developmental functioning. Young children
      with autism displayed a higher number of symptoms than those with PDD-NOS on all
      three domains of impairment (social, communication, repetitive behaviors). As
      expected, children without an ASD evinced far fewer symptoms than both these
      groups. Developmental level was not found to be a moderator for expression of ASD
      symptoms for the entire sample, or individual diagnostic groups. Higher
      developmental level was associated with lower severity of evinced ASD symptoms in
      the sample.

PMID- 23123871
TI  - Psychosocial effects of reverse-integrated basketball activity compared to
      separate and no physical activity in young people with physical disability.
AB  - The purpose of this study was to examine the impact of participation in different
      sport modalities on quality of life (QOL) and perceived social competence (PSC)
      in young people with physical disability. Ninety participants (33 females and 57
      males) were monitored across four conditions: competitive separate physical
      activity (COSPA), recreational separate physical activity (RESPA), reverse
      integrated basketball activity (RIBA), and no physical activity (NOPA). QOL and
      PSC questionnaires were administered at the beginning and the end of the study's
      duration of six months. ANCOVA corrected for functional independence and gender
      revealed significant group effects for pre to post change values of QOL and PSC,
      with greater positive change in the RIBA compared to all other groups. In
      addition, one-way ANOVA on pre to post change values with LSD post hoc revealed
      significant differences. RIBA change values for QOL with 8.77%, and for PSC with
      9.98% change were significantly higher (p<.001) than in all other groups (ranges 
      0.18 through 1.36% for QOL, and -2.31 through 2.34% for PSC). These outcomes
      demonstrate a favorable outcome of the RIBA on participants. Low functional
      ability did not constrain the effects of sport participation.

PMID- 23123872
TI  - Determinants of inclusive education of 8-12 year-old children with cerebral palsy
      in 9 European regions.
AB  - The principle of inclusive education has been increasingly recognised over recent
      decades and most countries officially support schooling of children with
      disabilities in mainstream settings. The SPARCLE study offers the opportunity to
      report on the schooling practices for children with cerebral palsy according to
      the nature and severity of their impairments and the schooling policy in European
      regions. The aim of this paper is to describe the type of schooling of children
      with cerebral palsy in various European regions after controlling for relevant
      individual factors. Children aged 8-12 years with cerebral palsy from 9 European
      regions and their families were interviewed. Our findings support the hypothesis
      that between-region variations in the type of schooling are still significant
      after adjustment for individual factors; and that motor function and intellectual
      ability have different effects on inclusion in mainstream school, depending on
      the region.

PMID- 23123874
TI  - The role of linguistic context in deriving word meanings in individuals with Down
      Syndrome.
AB  - Deriving the meaning of unknown words from context and its relationship to text
      comprehension was investigated in 24 individuals with Down syndrome and in 24
      typically developing children matched for the Peabody Picture Vocabulary Test
      (PPVT) score. The study consisted of three phases. Unknown words were identified
      during the first phase (PPVT). Those words were presented embedded in brief
      linguistic contexts during the second phase. Recognition (maintenance) of word
      meanings was verified in the third and final phase. Both groups of participants
      recognized the meanings of a noteworthy number of words in contexts and a high
      percentage of these was maintained when they were presented at a later date
      without the support of context. Over and above group differences and basic
      linguistic skills, text comprehension seems to predict the ability to use
      context. Context provides the semantic information necessary to extract word
      meaning by activating relevant world knowledge.

PMID- 23123873
TI  - An examination of specific daily living skills deficits in adults with profound
      intellectual disabilities.
AB  - While some researchers have investigated daily living skills deficits in
      individuals with intellectual disability (ID) as a whole, research on specific
      daily living skills in a profound ID population is limited. Two hundred and four
      adults with profound ID residing in two large developmental centers in the
      southeast portion of the United States were studied. Data were collected on these
      individuals' daily living skills, utilizing the Vineland Adaptive Behavior Scales
      (VABS). Three dependent t-tests were conducted comparing the proportion of items
      endorsed by informants on each of the three subdomains of daily living skills on
      the VABS (personal, domestic, and community). A significantly larger proportion
      of Personal Subdomain items were endorsed compared to Domestic or Community
      Subdomain items. Additionally, participants exhibited a significantly larger
      proportion of Domestic Skills Subdomain items compared to Community Skills
      Subdomain items which is consistent with theoretical models suggesting that
      institutional living may curb broader community skill sets. No gender differences
      were found in daily living skills. Lastly, individuals between the ages 30 and 39
      exhibited significantly more Personal Subdomain skills than individuals who were
      60 or older, while participants between the ages 30 and 39 exhibited
      significantly more Domestic Subdomain skills than individuals between the ages 60
      and 69.

PMID- 23123875
TI  - Gaze aversion during social style interactions in autism spectrum disorder and
      Williams syndrome.
AB  - During face-to-face interactions typically developing individuals use gaze
      aversion (GA), away from their questioner, when thinking. GA is also used when
      individuals with autism (ASD) and Williams syndrome (WS) are thinking during
      question-answer interactions. We investigated GA strategies during face-to-face
      social style interactions with familiar and unfamiliar interlocutors.
      Participants with WS and ASD used overall typical amounts/patterns of GA with all
      participants looking away most while thinking and remembering (in contrast to
      listening and speaking). However there were a couple of specific disorder related
      differences: participants with WS looked away less when thinking and interacting
      with unfamiliar interlocutors; in typical development and WS familiarity was
      associated with reduced gaze aversion, however no such difference was evident in
      ASD. Results inform typical/atypical social and cognitive phenotypes. We conclude
      that gaze aversion serves some common functions in typical and atypical
      development in terms of managing the cognitive and social load of interactions.
      There are some specific idiosyncracies associated with managing familiarity in
      ASD and WS with elevated sociability with unfamiliar others in WS and a lack of
      differentiation to interlocutor familiarity in ASD. Regardless of the familiarity
      of the interlocutor, GA is associated with thinking for typically developing as
      well as atypically developing groups. Social skills training must take this into
      account.

PMID- 23123876
TI  - When there seem to be no predetermining factors: early child and proximal family
      risk predicting externalizing behavior in young children incurring no distal
      family risk.
AB  - The main objective of the current study was to examine the impact of two child
      risk factors, i.e. personality and inhibition, and two proximal family risk
      factors, i.e. parenting and attachment, and the impact of their cumulative effect
      on later externalizing behavior among young children incurring no distal family
      risk. Data were collected in a longitudinal two-wave design from 161 non-referred
      and referred children aged three to five years at the onset of the study. All of
      the children were raised in families of middle to high socio-economic status,
      i.e. their parents were educated to a middle to high level, had access to the job
      market and lived together as couples. The four risk domains were assessed at the
      onset of the study, while EB was rated both at the onset of the study and in the
      24-month follow-up. Results confirmed that the four risk domains were each both
      correlates of EB and efficient at discriminating non-referred from referred
      children; that their combination regardless of their content (cumulative risk)
      provided a strong prediction of both later EB and non-referred vs referred sample
      membership. The results are discussed both for research and clinical purposes.

PMID- 23123877
TI  - Early identification of Asperger syndrome in young children.
AB  - This study was designed to identify items of the ADI-R that allow an early and
      sensitive identification of children with possible Asperger syndrome (AS). The
      aim was to obtain an economic short interview suitable for screening purposes.
      The study was based on data from a clinical sample of 5-18-year-old children and
      adolescents (mean age 10.9 years) with either Attention-Deficit Hyperactivity
      Disorder (ADHD; n = 43) or AS (n = 62). The introductory questions and 36 items,
      which contribute to the diagnostic algorithm of the ADI-R, were subjected to
      content analysis and stepwise discriminant function analysis. Eight meaningful
      items were found, which were shown to be good predictors of AS and to
      discriminate between the children with AS and those with ADHD. The short
      interview was especially useful for the assessment and screening of children up
      to 11 years in our sample, because in this subgroup, sensitivity was even higher
      (.92) and specificity was also excellent (.90). Eight items with high
      discriminatory power allowed sensitive and economic screening for young children
      with suspected AS.

PMID- 23123878
TI  - Predictors, including blood, urine, anthropometry, and nutritional indices, of
      all-cause mortality among institutionalized individuals with intellectual
      disability.
AB  - As the life expectancy of people with intellectual disability (ID) increases, it
      is becoming necessary to understand factors affecting survival. However,
      predictors that are typically assessed among healthy people have not been
      examined. Predictors of all-cause mortality, including blood, urine,
      anthropometry, and nutritional indices, were examined among institutionalized
      people with ID. This retrospective cohort study involved 316 participants (191
      males, 125 females; mean age, 36.5 +/- 10.5 years) at a public facility for
      people with ID in Ibaraki Prefecture, Japan. During the follow-up from the
      examination day in 1984-1992 through December 31, 2007 (mean follow-up, 18.6
      years), 44 deaths occurred. Mean age at death was 47.1 +/- 10.0 years (range,
      22.3-65.3 years). Early deaths within three years (n = 4) were treated as
      censored cases. Cox proportional hazard regression models were used to calculate
      hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause mortality.
      Sex- and age-adjusted analysis (p<0.15) revealed positive associations with
      mortality for high serum cholesterol, high thymol turbidity test (TTT), and
      glucosuria and negative associations with mortality for high serum albumin, high
      uric acid, high potassium, high calcium, and high systolic blood pressure.
      Multivariate analysis revealed that male sex (HR, 4.11; 95% CI, 1.59-10.59), high
      serum cholesterol (1.01; 1.00-1.02), high serum TTT (1.21; 1.03-1.41), and
      epilepsy significantly increased the mortality risk. The results indicate that
      the predictors of life expectancy for people with ID included both factors that
      are shared with healthy people (male sex, high serum cholesterol) and factors
      specific to people with disabilities (high serum TTT and epilepsy).

PMID- 23123879
TI  - Parent-child interaction of mothers with depression and their children with ADHD.
AB  - Attention deficit/hyperactivity disorder (ADHD) is a developmental disorder that
      may have a chronic and pervasive impact on the child's function and cause long
      term stress to parents. A higher rate of depression is associated with mothers of
      children with ADHD. This observational study aimed to investigate the effect of
      maternal depression and the child's ADHD on the quality of the parent-child
      interaction in children with ADHD and their mothers with depression. The study
      participants comprised 39 mother-son dyads including children with ADHD and
      mothers with depression, children with ADHD and mothers without depression, and
      children without ADHD and mothers without depression. The Specific Affect Coding
      System, 20-code version was used to code interactional affect, including positive
      engagement, negative engagement, negative disengagement, and neural affect. There
      were no statistically significant group-by-context interaction effects or group
      effects on all affective variables between the group of children with ADHD and
      mothers without depression and the group of children without ADHD and mothers
      without depression. Stimulant medication may account for these nonsignificant
      findings. No significant difference of positive affect between neutral and
      conflict-solving contexts was observed in depressed mothers whose children were
      diagnosed as ADHD. Children with ADHD whose mothers were depressed were less
      positive in their parent-child interaction compared with children in the other
      groups. Maternal depression may play an important role in the affective
      presentation of dyads of children with ADHD and mothers with depression.
      Implications for clinical practice and future research are provided.

PMID- 23123880
TI  - Spatial-simultaneous and spatial-sequential working memory in individuals with
      Down syndrome: the effect of configuration.
AB  - Earlier research showed that visuospatial working memory (VSWM) is better
      preserved in Down syndrome (DS) than verbal WM. Some differences emerged,
      however, when VSWM performance was broken down into its various components, and
      more recent studies revealed that the spatial-simultaneous component of VSWM is
      more impaired than the spatial-sequential one. The difficulty of managing more
      than one item at a time is also evident when the information to be recalled is
      structured. To further analyze this issue, we investigated the advantage of
      material being structured in spatial-simultaneous and spatial-sequential tasks by
      comparing the performance of a group of individuals with DS and a group of
      typically-developing children matched for mental age. Both groups were presented
      with VSWM tasks in which both the presentation format (simultaneous vs.
      sequential) and the type of configuration (pattern vs. random) were manipulated.
      Findings indicated that individuals with DS took less advantage of the pattern
      configuration in the spatial-simultaneous task than TD children; in contrast, the
      two groups' performance did not differ in the pattern configuration of the
      spatial-sequential task. Taken together, these results confirmed difficulties
      relating to the spatial-simultaneous component of VSWM in individuals with DS,
      supporting the importance of distinguishing between different components within
      this system. The findings are discussed in terms of factors influencing this
      specific deficit.

PMID- 23123881
TI  - Evaluation of a behavioral treatment package to reduce sleep problems in children
      with Angelman Syndrome.
AB  - The purpose of this investigation was to evaluate the effectiveness of a
      behavioral treatment package to reduce chronic sleep problems in children with
      Angelman Syndrome. Participants were five children, 2-11 years-of-age. Parents
      maintained sleep diaries to record sleep and disruptive nighttime behaviors.
      Actigraphy was added to provide independent evaluations of sleep-wake activity.
      The treatment package targeted the sleep environment, the sleep-wake schedule,
      and parent-child interactions during sleep times. Treatment was introduced
      sequentially, across families, and evaluated in an interrupted time series,
      multiple baseline design. Data show that prior to treatment, baseline rates of
      nighttime disruptive behavior were stable or increasing and none of the
      participants were falling to sleep independently. With the introduction of
      treatment, all participants quickly learned to initiate sleep independently.
      Gradual reductions were reported in disruptive behaviors and these improvements
      were sustained over time. Results were replicated with two participants when
      treatment was withdrawn and reinstated. Changes in disruptive bedtime behaviors
      and in sleep onset were found to be statistically significant. Parents indicated
      high satisfaction with the treatment. A behavioral treatment package was found to
      be effective with five children with long histories of significant sleep-related
      behavior problems. These results suggest that behavioral treatment may be a
      reasonable way to address sleep problems in some children with Angelman Syndrome.

PMID- 23123882
TI  - Everyday memory in children with developmental coordination disorder.
AB  - Children with developmental coordination disorder (DCD) have deficits in working
      memory, but little is known about the everyday memory of these children in real
      life situations. We investigated the everyday memory function in children with
      DCD, and explored the specific profile of everyday memory across different
      domains. Nineteen children with DCD and 19 typically developing (TD) children
      participated in the study. Their everyday memory performance was evaluated using
      the Rivermead Behavioral Memory Test for Children, which showed that 52.6% of the
      children with DCD had everyday memory deficits. The overall everyday memory
      scores of the DCD group were significantly lower than those of the controls,
      particularly in the verbal and visual memory domains. Pearson correlation
      analysis indicated significant associations between verbal intelligence and
      memory scores. Analysis of covariance with verbal intelligence as a covariate
      showed no significant differences between groups in memory scores. Mediator
      analysis supported the notion that everyday memory deficits in children with DCD
      were fully mediated through verbal intelligence. We provide evidence of everyday
      memory deficits in most of the children with DCD, and hypothesize that language
      abilities are their underlying cause. The clinical implications of these findings
      and recommendations for additional research are discussed.

PMID- 23123883
TI  - Effects of fluid shear stress on the expression of Omi/HtrA2 in human umbilical
      vein endothelial cells.
AB  - To investigate the molecular mechanisms of laminar shear stress on the inhibition
      of apoptosis in endothelial cells, human umbilical vein endothelial cells
      (HUVECs) were starved in medium containing 2% fetal bovine serum (FBS) and
      treated with 15 dyne/cm2 shear stress. We confirmed that 15 dyne/cm2 shear stress
      inhibited the expression of Omi/HtrA2 at the mRNA and protein levels in cultured
      HUVECs. Furthermore, the release of Omi/HtrA2 from the mitochondria was induced
      by removal of basic fibroblast growth factor and decrease of FBS in the medium,
      while shear stress inhibited its release under the same conditions. These results
      suggest that downregulation of Omi/HtrA2 may contribute to the potent anti
      atherosclerotic effect of shear stress by preventing endothelial cells from
      entering apoptosis. 

PMID- 23123884
TI  - Retraction: Incidence Study of Brucella abortus and Brucella melitensis in Bovine
      and Buffalo Semen Samples by Real-Time PCR Assay in Iran.
AB  - This article released online on August 3, 2012 as advance publication was
      withdrawn from consideration for publication in The Journal of Veterinary Medical
      Science at author's request.

PMID- 23123885
TI  - Pathological features of polyneuropathy in three dogs.
AB  - Canine polyneuropathy is a neurological disorder characterized by a dysfunction
      of multiple peripheral nerves. The etiology of the disease is diverse; it may
      occur in cases of infectious, immune-mediated, or hereditary conditions or in
      association with endocrinopathy, neoplasm, or chemical intoxication. It is often
      difficult to determine the etiology through clinical symptoms. The aim of this
      study is to investigate pathological differences among three canine
      polyneuropathy cases with each presumably having a different etiology. Cases
      included a 13-month-old female border collie (Dog No.1), a 21-month-old male
      chihuahua (Dog No.2) and an 11-year-old male beagle (Dog No.3). Clinical
      examinations revealed hindlimb ataxia and sensory loss in Dog No.1, forelimb
      paralysis and vertebral pain in Dog No.2, and paddling-gait and hypothyroidism in
      Dog No.3. Histopathologically, axonal swelling and pale myelin were observed in
      Dog No.1. Giant axons mimicking giant axonal neuropathy were obvious in Dog No.2.
      Dog No.3 showed atrophic axons and severe interstitial edema. Distributions of
      peripheral nerve lesions coincided with respective clinical symptoms. According
      to their clinical and pathological features, Dogs No.1 and No.2 were suspected of
      hereditary polyneuropathy, while Dog No.3 seemed to have hypothyroidism
      associated polyneuropathy. As each case demonstrated unique pathological
      features, different pathogeneses of peripheral nerve dysfunction were suggested.

PMID- 23123888
TI  - The image of nursing.

PMID- 23123886
TI  - Testosterone and brain-derived neurotrophic factor interactions in the avian song
      control system.
AB  - Interaction between steroid sex hormones and brain-derived neurotrophic factor
      (BDNF) is a common feature of vertebrate brain organization. The avian song
      control system provides an excellent model for studying such interactions in
      neural circuits that regulate song, a learned sensorimotor behavior that is often
      sexually dimorphic and restricted to reproductive contexts. Testosterone (T) and
      its steroid metabolites interact with BDNF during development of the song system
      and in adult plasticity, including the addition of newborn neurons to the pallial
      nucleus HVC and seasonal changes in structure and function of these circuits. T
      and BDNF interact locally within HVC to influence cell proliferation and
      survival. This interaction may also occur transsynpatically; T increases the
      synthesis of BDNF in HVC, and BDNF protein is then released on to postsynaptic
      cells in the robust nucleus of the arcopallium (RA) where it has trophic effects.
      The interaction between sex steroids and BDNF is an example of molecular
      exploitation, with the evolutionarily ancient steroid-receptor complex having
      been captured by the more recently evolved BDNF. The functional linkage of sex
      steroids to BDNF may be of adaptive value in regulating the trophic effects of
      the neurotrophin in sexually dimorphic and reproductively relevant contexts.

PMID- 23123887
TI  - Neuroanatomical study on the tecto-suprageniculate-dorsal auditory cortex pathway
      in the rat.
AB  - Previous anatomical and physiological studies suggest that the superior
      colliculus sends integrated sensory information to the multimodal cortical areas
      via the thalamic suprageniculate nucleus (SG). However, the detailed distribution
      of rat tecto-SG axon terminals and SG neurons projecting to the multimodal
      cortex, as well as synaptic connections between these tectal axons and SG
      neurons, remains unclear. In this study, the organization of the tecto-thalamo
      cortical pathway was investigated via combined injections of anterograde and
      retrograde tracers followed by light and electron microscopic observations.
      Injections of a retrograde tracer, cholera toxin B subunit (CTB), into the
      temporal cortex, area 2, dorsal part (Te2D), and injections of an anterograde
      tracer, biotinylated dextran amine (BDA), into the deep layers of the superior
      colliculus produced the following results: (1) Retrogradely CTB-labeled neurons
      were found throughout SG, predominantly in its rostral part. CTB-labeled neurons
      were also found in other cortical areas such as the visual cortex, the auditory
      cortex, the parietal association cortex, and the perirhinal cortex. (2)
      Anterogradely BDA-labeled axons and their terminals were also observed throughout
      SG. Dual visualization of BDA and CTB showed that retrogradely labeled SG neurons
      and anterogradely labeled tectal axon terminal boutons overlapped considerably in
      the rostral part of SG, and their direct synaptic contacts were also confirmed
      via electron microscopy. These findings suggest that multimodal information from
      the superior colliculus can be processed directly in SG neurons projecting to
      Te2D.

PMID- 23123889
TI  - Proposing a cardiac model for vascular dementia.

PMID- 23123890
TI  - Quality of life after percutaneous coronary intervention: part 2.
AB  - This is the second in a two-part series on quality of life (QoL) after
      percutaneous coronary intervention (PCI). Part I presented the research
      methodology of this retrospective cross-sectional descriptive study that
      investigated the QoL of a systematic sample of clients after PCI with a response
      rate of 64% (n=228; menn=169, women n=59; age 40-89 years). Quantitative data was
      collected using the Maltese version of the mailed WHOQoL-BREF questionnaire. The
      study aimed to identify significant differences in QoL between subgroups of
      clients according to demographic characteristics and their perceived
      cardiovascular risk factors.Significant differences were found in the overall QoL
      between subgroups of gender,education, occupation, friends' support and stress.
      The domain of social support,which is characteristic of Maltese culture, appeared
      to yield high mean scores of the overall QoL, irrespective of cardiovascular risk
      factors, such as smoking and alack of physical exercise. Hence, social
      relationships may enhance QoL as they mayyield security in life, feelings of love
      and belonging to a community. Perceived stress and social support seemed to
      generate significant differences in QoL. Although these findings were consistent
      with existing research, the use of different operational definitions of QoL means
      they cannot be compared accurately. While considering the limitations of this
      study, recommendations addressed the need for holistic assessment of patients'
      needs, education, follow-up monitoring and community services. Further
      comparative longitudinal research is recommended to identify confounding
      variables and fluctuation of results across time.

PMID- 23123891
TI  - The role of the nurse practitioner within the Hospital at Night service.
AB  - The Hospital at Night (HaN) service uses a multidisciplinary approach to
      prioritise the care of acutely ill patients overnight. Nurse practitioners (NPs)
      play a key role in coordinating this service and provide support to ward-based
      staff. Despite evidence that HaN can positively impact on patient care, it may be
      met with scepticism owing to changes in how acutely ill patients are assessed
      overnight. The aim of this study was to identify the perceptions held by nursing
      and medical staff on the NP role within HaN. A sample of 46 nurses and 52 doctors
      in an acute hospital completed questionnaires, which were developed based on
      components of the nurse practitioner role description. Staff's perceptions were
      generally similar regarding most role components. However, some variations were
      identified about components such as patient assessment and teaching. Scheduled
      education sessions can potentially increase staff awareness of NP roles and
      improve staff collaboration around patients' care overnight.

PMID- 23123892
TI  - Addressing appearance-related distress across clinical conditions.
AB  - Evidence is accumulating about the nature and prevalence of appearance-related
      distress across a variety of clinical populations. Health professionals working
      with specific patient groups are often aware of these difficulties and their
      detrimental effect on quality of life and wellbeing. However, many health
      professionals lack knowledge and skills on how to support patients, either within
      the team or via referral to relevant service providers who have expertise in
      managing appearance-related distress. This is mainly owing to a lack of
      information about screening, assessment measures and available interventions. The
      aim of this article is to consider how health professionals can support patients
      who experience distress as a result of living with a long-term physical health
      condition that has altered their appearance. This article summarises the
      challenges for patients and health professionals surrounding body image, altered
      appearance and associated distress. Gaps in relation to screening measures,
      differing types of intervention, appearance-related skills training for
      healthcare teams, care pathways and access to services are identified. A summary
      of the limited range of interventions currently available has been mapped onto a
      stepped model of care, ranging from self-help to intensive therapies. Finally,
      readers are pointed to helpful resources for understanding, identifying,
      addressing and signposting patients with appearance-related distress.

PMID- 23123893
TI  - The role of the ward manager in promoting patient safety.
AB  - In this article the role of the ward manager in promoting patient safety is
      explored. The background to the development of the patient safety agenda is
      briefly discussed and the relationship between quality and safety is illustrated.
      The pivotal importance of the role of the ward manager in delivering services to
      patients is underlined and literature on patient safety is examined to identify
      what a ward manager can do to make care safer.  Possible actions of the ward
      manager to improve safety discussed in the literature are structured around the
      Leadership Framework. This framework identifies seven domains for the leadership
      of service delivery. Ward managers use their personal qualities, and network and
      work within teams, while managing performance and facilitating innovation, change
      and measurement for improvement. The challenge of promoting patient safety for
      ward managers is briefly explored and recommendations for further research are
      made.

PMID- 23123894
TI  - Nursing home residents' challenges with socialisation: can nurses help?
AB  - Nursing home residents experience significant changes in their social and
      emotional connections as a result of the unique challenges associated with their
      environment. One of the greatest changes is with whom they communicate on a day
      to-day basis. It is essential that social integration and, subsequently, social
      bonds develop in order to reinforce a sense of person, confidence, and hope.
      However, there are multiple and varied factors, such as cognitive impairment of
      other residents, which make building meaningful relationships especially
      challenging. This article investigates the challenges confronting cognitively
      intact nursing home residents and their impact toward successful socialisation in
      their environment. Based on findings in the literature, recommendations for
      strategies that nurses can use to promote a sense of community and feelings of
      being at home for residents are explored and areas for research identified.

PMID- 23123895
TI  - Medicines non-adherence: adult literacy and implications for practice.
AB  - Functional health literacy is defined as the level at which individuals can
      obtain, process and understand basic health information (Martin et al, 2009).
      Government statistics suggest low functional health literacy is an under
      recognised and growing problem in UK health care. It is associated with high
      hospitalisation (Baker et al, 1998) and increased medicines non-adherence
      (Kalichman et al, 1999). Health professionals are poor at assessing and
      identifying those at risk because they have yet to acknowledge the prevalence of
      the problem. Initiatives attempting to address medicines non-adherence promote
      patient involvement in treatment decisions but remain ineffective if patients
      cannot read or understand written instructions. To help patients with low
      functional health literacy practitioners should speak slowly, repeat information,
      use plain, non-medical language and adopt teach-back techniques. These actions
      take extra time but are relatively easy to adopt and with a little thought become
      part of everyday practice.

PMID- 23123896
TI  - Assistant practitioners: lessons learned from licensed practical nurses.
AB  - The role of the assistant practitioner (AP) needs to be defined so they have
      clear career pathways and opportunities for professional development. The author
      sought to learn from other countries where a sustained effort had been made to
      support practitioners fulfilling this intermediate role. The equivalent of an AP
      in Canada is the licensed practical nurse (LPN); LPNs are subject to clear
      regulation and practice within their remit of their license. The author travelled
      to Alberta, Canada, and performed a qualitative study to investigate the role of
      the LPN. LPNs undertake a 2-year diploma-level course and have the opportunity to
      enhance their careers through specialist courses or to train as a RN. LPNs
      benefit from careful regulation, enabling them to have a clear scope of practice,
      a career structure with opportunities for development and consistent ethical
      standards. Lessons can be learned from the LPN model and put in practice in the
      UK; APs need a consistent education programme, a career pathway that promotes
      development and effective regulation.

PMID- 23123898
TI  - A compassionate vision  for nursing and midwifery.

PMID- 23123897
TI  - The rollercoaster of life  as a student nurse.

PMID- 23123899
TI  - Teaching and Learning: from staff nurse to nurse consultant. Part 9: public
      speaking and lectures.

PMID- 23123900
TI  - The Patients Association wake-up call to primary health care.

PMID- 23123901
TI  - Human resources for health  care: a global issue?

PMID- 23123902
TI  - Whose choice is it anyway?

PMID- 23123903
TI  - The Bacillus subtilis response regulator gene degU is positively regulated by
      CcpA and by catabolite-repressed synthesis of ClpC.
AB  - In Bacillus subtilis, the response regulator DegU and its cognate kinase, DegS,
      constitute a two-component system that regulates many cellular processes,
      including exoprotease production and genetic competence. Phosphorylated DegU
      (DegU-P) activates its own promoter and is degraded by the ClpCP protease. We
      observed induction of degU by glucose in sporulation medium. This was abolished
      in two mutants: the ccpA (catabolite control protein A) and clpC disruptants.
      Transcription of the promoter of the operon containing clpC (PclpC) decreased in
      the presence of glucose, and the disruption of ccpA resulted in derepression of
      PclpC. However, this was not directly mediated by CcpA, because we failed to
      detect binding of CcpA to PclpC. Glucose decreased the expression of clpC,
      leading to low cellular concentrations of the ClpCP protease. Thus, degU is
      induced through activation of autoregulation by a decrease in ClpCP-dependent
      proteolysis of DegU-P. An electrophoretic mobility shift assay showed that CcpA
      bound directly to the degU upstream region, indicating that CcpA activates degU
      through binding. The bound region was narrowed down to 27 bases, which contained
      a cre (catabolite-responsive element) sequence with a low match to the cre
      consensus sequence. In a footprint analysis, CcpA specifically protected a region
      containing the cre sequence from DNase I digestion. The induction of degU by
      glucose showed complex regulation of the degU gene.

PMID- 23123904
TI  - Role of Pseudomonas aeruginosa peptidoglycan-associated outer membrane proteins
      in vesicle formation.
AB  - Gram-negative bacteria produce outer membrane vesicles (OMVs) that package and
      deliver proteins, small molecules, and DNA to prokaryotic and eukaryotic cells.
      The molecular details of OMV biogenesis have not been fully elucidated, but
      peptidoglycan-associated outer membrane proteins that tether the outer membrane
      to the underlying peptidoglycan have been shown to be critical for OMV formation
      in multiple Enterobacteriaceae. In this study, we demonstrate that the
      peptidoglycan-associated outer membrane proteins OprF and OprI, but not OprL,
      impact production of OMVs by the opportunistic pathogen Pseudomonas aeruginosa.
      Interestingly, OprF does not appear to be important for tethering the outer
      membrane to peptidoglycan but instead impacts OMV formation through modulation of
      the levels of the Pseudomonas quinolone signal (PQS), a quorum signal previously
      shown by our laboratory to be critical for OMV formation. Thus, the mechanism by
      which OprF impacts OMV formation is distinct from that for other peptidoglycan
      associated outer membrane proteins, including OprI.

PMID- 23123905
TI  - 2-nitrobenzoate 2-nitroreductase (NbaA) switches its substrate specificity from 2
      nitrobenzoic acid to 2,4-dinitrobenzoic acid under oxidizing conditions.
AB  - 2-Nitrobenzoate 2-nitroreductase (NbaA) of Pseudomonas fluorescens strain KU-7 is
      a unique enzyme, transforming 2-nitrobenzoic acid (2-NBA) and 2,4-dinitrobenzoic
      acid (2,4-DNBA) to the 2-hydroxylamine compounds. Sequence comparison reveals
      that NbaA contains a conserved cysteine residue at position 141 and two variable
      regions at amino acids 65 to 74 and 193 to 216. The truncated mutant Delta65-74
      exhibited markedly reduced activity toward 2,4-DNBA, but its 2-NBA reduction
      activity was unaffected; however, both activities were abolished in the Delta193
      216 mutant, suggesting that these regions are necessary for the catalysis and
      specificity of NbaA. NbaA showed different lag times for the reduction of 2-NBA
      and 2,4-DNBA with NADPH, and the reduction of 2,4-DNBA, but not 2-NBA, failed in
      the presence of 1 mM dithiothreitol or under anaerobic conditions, indicating
      oxidative modification of the enzyme for 2,4-DNBA. The enzyme was irreversibly
      inhibited by 5,5'-dithio-bis-(2-nitrobenzoic acid) and ZnCl(2), which bind to
      reactive thiol/thiolate groups, and was eventually inactivated during the
      formation of higher-order oligomers at high pH, high temperature, or in the
      presence of H(2)O(2). SDS-PAGE and mass spectrometry revealed the formation of
      intermolecular disulfide bonds by involvement of the two cysteines at positions
      141 and 194. Site-directed mutagenesis indicated that the cysteines at positions
      39, 103, 141, and 194 played a role in changing the enzyme activity and
      specificity toward 2-NBA and 2,4-DNBA. This study suggests that oxidative
      modifications of NbaA are responsible for the differential specificity for the
      two substrates and further enzyme inactivation through the formation of disulfide
      bonds under oxidizing conditions.

PMID- 23123906
TI  - Roles of AtpI and two YidC-type proteins from alkaliphilic Bacillus pseudofirmus
      OF4 in ATP synthase assembly and nonfermentative growth.
AB  - AtpI, a membrane protein encoded by many bacterial atp operons, is reported to be
      necessary for c-ring oligomer formation during assembly of some ATP synthase
      complexes. We investigated chaperone functions of AtpI and compared them to those
      of AtpZ, a protein encoded by a gene upstream of atpI that has a role in
      magnesium acquisition at near-neutral pH, and of SpoIIIJ and YqjG, two
      YidC/OxaI/Alb3 family proteins, in alkaliphilic Bacillus pseudofirmus OF4. A
      strain with a chromosomal deletion of atpI grew nonfermentatively, and its
      purified ATP synthase had a c-ring of normal size, indicating that AtpI is not
      absolutely required for ATP synthase function. However, deletion of atpI, but not
      atpZ, led to reduced stability of the ATP synthase rotor, reduced membrane
      association of the F(1) domain, reduced ATPase activity, and modestly reduced
      nonfermentative growth on malate at both pH 7.5 and 10.5. Both spoIIIJ and yqjG,
      but not atpI or atpZ, complemented a YidC-depleted Escherichia coli strain.
      Consistent with such overlapping functions, single deletions of spoIIIJ or yqjG
      in the alkaliphile did not affect membrane ATP synthase levels or activities, but
      functional specialization was indicated by YqjG and SpoIIIJ showing respectively
      greater roles in malate growth at pH 7.5 and 10.5. Expression of yqjG was
      elevated at pH 7.5 relative to that at pH 10.5 and in DeltaspoIIIJ strains, but
      it was lower than constitutive spoIIIJ expression. Deletion of atpZ caused the
      largest increase among the mutants in magnesium concentrations needed for pH 7.5
      growth. The basis for this phenotype is not yet resolved.

PMID- 23123908
TI  - Role of homologous recombination in adaptive diversification of extraintestinal
      Escherichia coli.
AB  - The contribution of homologous exchange (recombination) of core genes in the
      adaptive evolution of bacterial pathogens is not well understood. To investigate
      this, we analyzed fully assembled genomes of two Escherichia coli strains from
      sequence type 131 (ST131), a clonal group that is both the leading cause of
      extraintestinal E. coli infections and the main source of fluoroquinolone
      resistant E. coli. Although the sequences of each of the seven multilocus
      sequence typing genes were identical in the two ST131 isolates, the strains
      diverged from one another by homologous recombination that affected at least 9%
      of core genes. This was on a par with the contribution to genomic diversity of
      horizontal gene transfer and point gene mutation. The genomic positions of
      recombinant and mobile genetic regions were partially linked, suggesting their
      concurrent occurrence. One of the genes affected by homologous recombination was
      fimH, which encodes mannose-specific type 1 fimbrial adhesin, resulting in
      functionally distinct copies of the gene in ST131 strains. One strain, a
      uropathogenic isolate, had a pathoadaptive variant of fimH that was acquired by
      homologous replacement into the commensal strain background. Close examination of
      FimH structure and function in additional ST131 isolates revealed that
      recombination led to acquisition of several functionally distinct variants that,
      upon homologous exchange, were targeted by a variety of pathoadaptive mutations
      under strong positive selection. Different recombinant fimH strains also showed a
      strong clonal association with ST131 isolates that had distinct fluoroquinolone
      resistance profiles. Thus, homologous recombination of core genes plays a
      significant role in adaptive diversification of bacterial pathogens, especially
      at the level of clonally related groups of isolates.

PMID- 23123907
TI  - The tRNAarg gene and engA are essential genes on the 1.7-Mb pSymB megaplasmid of
      Sinorhizobium meliloti and were translocated together from the chromosome in an
      ancestral strain.
AB  - Bacterial genomes with two (or more) chromosome-like replicons are known, and
      these appear to be particularly frequent in alphaproteobacteria. The genome of
      the N(2)-fixing alfalfa symbiont Sinorhizobium meliloti 1021 contains a 3.7-Mb
      chromosome and 1.4-Mb (pSymA) and 1.7-Mb (pSymB) megaplasmids. In this study, the
      tRNA(arg) and engA genes, located on the pSymB megaplasmid, are shown to be
      essential for growth. These genes could be deleted from pSymB when copies were
      previously integrated into the chromosome. However, in the closely related strain
      Sinorhizobium fredii NGR234, the tRNA(arg) and engA genes are located on the
      chromosome, in a 69-kb region designated the engA-tRNA(arg)-rmlC region. This
      region includes bacA, a gene that is important for intracellular survival during
      host-bacterium interactions for S. meliloti and the related alphaproteobacterium
      Brucella abortus. The engA-tRNA(arg)-rmlC region lies between the kdgK and dppF2
      (NGR_c24410) genes on the S. fredii chromosome. Synteny analysis showed that kdgK
      and dppF2 orthologues are adjacent to each other on the chromosomes of 15
      sequenced strains of S. meliloti and Sinorhizobium medicae, whereas the 69-kb
      engA-tRNA(arg)-rmlC region is present on the pSymB-equivalent megaplasmids. This
      and other evidence strongly suggests that the engA-tRNA(arg)-rmlC region
      translocated from the chromosome to the progenitor of pSymB in an ancestor common
      to S. meliloti and S. medicae. To our knowledge, this work represents one of the
      first experimental demonstrations that essential genes are present on a
      megaplasmid.

PMID- 23123909
TI  - PhoY2 of mycobacteria is required for metabolic homeostasis and stress response.
AB  - The ability of pathogenic mycobacteria to adapt to diverse environments is
      essential for their success as pathogens. Here we describe a transposon
      inactivated phoY2 mutant of Mycobacterium marinum. PhoY2 of mycobacteria is a
      functional homologue of PhoU in Escherichia coli and an important component of
      the Pho regulon. We found that PhoY2 is required for maintaining intracellular
      inorganic phosphate (P(i)) homeostasis and balanced energy and redox states.
      Disruption of phoY2 resulted in elevated levels of intracellular poly-P(i) and
      ATP and an elevated NAD(+)/NADH ratio, and the mutant strain exhibited increased
      sensitivity to environmental stress conditions, including nutrient deprivation as
      well as SDS and antibiotic treatments. Taken together, our results suggest that
      PhoY2 is required for maintaining metabolic homeostasis and adaptation to stress
      conditions, which may provide an explanation for the suggested role of PhoY2 in
      drug tolerance.

PMID- 23123910
TI  - Gliding motility and Por secretion system genes are widespread among members of
      the phylum bacteroidetes.
AB  - The phylum Bacteroidetes is large and diverse, with rapid gliding motility and
      the ability to digest macromolecules associated with many genera and species.
      Recently, a novel protein secretion system, the Por secretion system (PorSS), was
      identified in two members of the phylum, the gliding bacterium Flavobacterium
      johnsoniae and the nonmotile oral pathogen Porphyromonas gingivalis. The
      components of the PorSS are not similar in sequence to those of other well
      studied bacterial secretion systems. The F. johnsoniae PorSS genes are a subset
      of the gliding motility genes, suggesting a role for the secretion system in
      motility. The F. johnsoniae PorSS is needed for assembly of the gliding motility
      apparatus and for secretion of a chitinase, and the P. gingivalis PorSS is
      involved in secretion of gingipain protease virulence factors. Comparative
      analysis of 37 genomes of members of the phylum Bacteroidetes revealed the
      widespread occurrence of gliding motility genes and PorSS genes. Genes associated
      with other bacterial protein secretion systems were less common. The results
      suggest that gliding motility is more common than previously reported.
      Microscopic observations confirmed that organisms previously described as
      nonmotile, including Croceibacter atlanticus, "Gramella forsetii," Paludibacter
      propionicigenes, Riemerella anatipestifer, and Robiginitalea biformata, exhibit
      gliding motility. Three genes (gldA, gldF, and gldG) that encode an apparent ATP
      binding cassette transporter required for F. johnsoniae gliding were absent from
      two related gliding bacteria, suggesting that the transporter may not be central
      to gliding motility.

PMID- 23123911
TI  - Missense mutations in cytochrome c maturation genes provide new insights into
      Rhodobacter capsulatus cbb3-type cytochrome c oxidase biogenesis.
AB  - The Rhodobacter capsulatus cbb(3)-type cytochrome c oxidase (cbb(3)-Cox) belongs
      to the heme-copper oxidase superfamily, and its subunits are encoded by the
      ccoNOQP operon. Biosynthesis of this enzyme is complex and needs dedicated
      biogenesis genes (ccoGHIS). It also relies on the c-type cytochrome maturation
      (Ccm) process, which requires the ccmABCDEFGHI genes, because two of the cbb(3)
      Cox subunits (CcoO and CcoP) are c-type cytochromes. Recently, we reported that
      mutants lacking CcoA, a major facilitator superfamily type transporter, produce
      very small amounts of cbb(3)-Cox unless the growth medium is supplemented with
      copper. In this work, we isolated "Cu-unresponsive" derivatives of a ccoA
      deletion strain that exhibited no cbb(3)-Cox activity even upon Cu
      supplementation. Molecular characterization of these mutants revealed missense
      mutations in the ccmA or ccmF gene, required for the Ccm process. As expected, Cu
      unresponsive mutants lacked the CcoO and CcoP subunits due to Ccm defects, but
      remarkably, they contained the CcoN subunit of cbb(3)-Cox. Subsequent
      construction and examination of single ccm knockout mutants demonstrated that
      membrane insertion and stability of CcoN occurred in the absence of the Ccm
      process. Moreover, while the ccm knockout mutants were completely incompetent for
      photosynthesis, the Cu-unresponsive mutants grew photosynthetically at lower
      rates and produced smaller amounts of cytochromes c(1) and c(2) than did a wild
      type strain due to their restricted Ccm capabilities. These findings demonstrate
      that different levels of Ccm efficiency are required for the production of
      various c-type cytochromes and reveal for the first time that maturation of the
      heme-Cu-containing subunit CcoN of R. capsulatus cbb(3)-Cox proceeds
      independently of that of the c-type cytochromes during the biogenesis of this
      enzyme.

PMID- 23123912
TI  - Gene conservation among endospore-forming bacteria reveals additional sporulation
      genes in Bacillus subtilis.
AB  - The capacity to form endospores is unique to certain members of the low-G+C group
      of Gram-positive bacteria (Firmicutes) and requires signature sporulation genes
      that are highly conserved across members of distantly related genera, such as
      Clostridium and Bacillus. Using gene conservation among endospore-forming
      bacteria, we identified eight previously uncharacterized genes that are enriched
      among endospore-forming species. The expression of five of these genes was
      dependent on sporulation-specific transcription factors. Mutants of none of the
      genes exhibited a conspicuous defect in sporulation, but mutants of two, ylxY and
      ylyA, were outcompeted by a wild-type strain under sporulation-inducing
      conditions, but not during growth. In contrast, a ylmC mutant displayed a slight
      competitive advantage over the wild type specific to sporulation-inducing
      conditions. The phenotype of a ylyA mutant was ascribed to a defect in spore
      germination efficiency. This work demonstrates the power of combining
      phylogenetic profiling with reverse genetics and gene-regulatory studies to
      identify unrecognized genes that contribute to a conserved developmental process.

PMID- 23123913
TI  - Role of binding in Mycoplasma mobile and Mycoplasma pneumoniae gliding analyzed
      through inhibition by synthesized sialylated compounds.
AB  - Mycoplasmas, which have been shown to be the causative pathogens in recent human
      pneumonia epidemics, bind to solid surfaces and glide in the direction of the
      membrane protrusion at a pole. During gliding, the legs of the mycoplasma catch,
      pull, and release sialylated oligosaccharides fixed on a solid surface.
      Sialylated oligosaccharides are major structures on animal cell surfaces and are
      sometimes targeted by pathogens, such as influenza virus. In the present study,
      we analyzed the inhibitory effects of 16 chemically synthesized sialylated
      compounds on the gliding and binding of Mycoplasma mobile and Mycoplasma
      pneumoniae and concluded the following. (i) The recognition of sialylated
      oligosaccharide by mycoplasma legs proceeds in a "lock-and-key" fashion, with the
      binding affinity dependent on structural differences among the sialylated
      compounds examined. (ii) The binding of the leg and the sialylated
      oligosaccharide is cooperative, with Hill constants ranging from 2 to 3. (iii)
      Mycoplasma legs may generate a drag force after a stroke, because the gliding
      speed decreased and pivoting motion occurred more frequently when the number of
      working legs was reduced by the addition of free sialylated compounds.

PMID- 23123914
TI  - Streptomycin interference in Jaffe reaction - possible false positive creatinine
      estimation in excessive dose exposure.
AB  - OBJECTIVES: To study the potential of commonly used aminoglycoside antibiotics to
      form non-creatinine chromogen with alkaline picrate reagent. DESIGN AND METHODS:
      We studied the non-creatinine chromogen formation of various concentrations of
      streptomycin, amikacin, kanamycin, netilmicin, gentamicin and tobramycin added to
      known creatinine concentrations by the Jaffe reaction based creatinine
      estimation. RESULTS: Only streptomycin above therapeutic concentrations of
      10mg/mL interfered in the Jaffe reaction and acted as non-creatinine chromogen.
      CONCLUSIONS: Therapeutic doses of the aminoglycosides do not form non-creatinine
      chromogens.

PMID- 23123916
TI  - Can a single "powerless" mitochondrion in the malaria parasite contribute to
      parasite programmed cell death in the asexual stages?
AB  - The protozoan pathogens responsible for malaria are from the Plasmodium genus,
      with Plasmodium falciparum and Plasmodium vivax accounting for almost all
      clinical infections. With recent estimates of mortality exceeding 800,000
      annually, malaria continues to take a terrible toll on lives and the early
      promises of medicine to eradicate the disease have yet to approach realization,
      in part due to the spread of drug resistant parasites. Recent reports of
      artemisinin-resistance have prompted renewed efforts to identify novel
      therapeutic options, and one such pathway being considered for antimalarial
      exploit is the parasite's programmed cell death (PCD) pathway. In this mini
      review, we will discuss the roles of the plasmodium mitochondria in cell death
      and as a target of antimalarial compounds, taking into account recent data
      suggesting that PCD pathways involving the mitochondria may be attractive
      antimalarial targets.

PMID- 23123917
TI  - In Vitro assessment of the utility of stearyl triphenyl phosphonium modified
      liposomes in overcoming the resistance of ovarian carcinoma Ovcar-3 cells to
      paclitaxel.
AB  - Paclitaxel loaded in liposomes modified with stearyl triphenyl phosphonium (STPP)
      showed improved mitochondrial colocalization and cytotoxicity in a paclitaxel
      resistant cell line. The improvement in cytotoxicity was not solely due to the
      increased accumulation of paclitaxel in mitochondria but also due to the specific
      toxicity of STPP towards the resistant cell line. Mechanistic studies revealed
      that the cytotoxicity of STPP was associated with a decrease in mitochondrial
      membrane potential and other hallmarks related to caspase-independent cell death
      (CICD). This specific toxicity of STPP towards the paclitaxel resistant cell line
      was also maintained in three-dimensional in vitro spheroid cultures. 

PMID- 23123918
TI  - Exploiting endobiotic metabolic pathways to target xenobiotic antioxidants to
      mitochondria.
AB  - Oxidative stress plays a role in a range of human disease entities. Hence,
      strategies to target antioxidants to mitochondria are an active area of
      investigation. Triphenylphosphonium cation-based antioxidants and SS-peptides
      have been described and show significant uptake by mitochondria and effectiveness
      in animal models of conditions linked to oxidative stress. We tested the
      hypothesis that the mitochondrial beta-oxidation pathway could be exploited to
      activate the antioxidant phenolic and methimazole prodrugs. Most compounds
      studied underwent mitochondrial biotransformation to release their antioxidant
      moieties, and some were cytoprotective in a hypoxia-reoxygenation model in rat
      cardiomyocytes. These results demonstrate the feasibility of exploiting
      mitochondrial bioactivation reactions for targeted drug delivery. 

PMID- 23123919
TI  - Different functions of hyperpolarization-activated cation channels for
      hippocampal sharp waves and ripples in vitro.
AB  - Hyperpolarization-activated currents (I(h)) affect multiple neuronal functions
      including membrane potential, intrinsic firing properties, synaptic integration
      and frequency-dependent resonance behavior. Consistently, I(h) plays a key role
      for oscillations at the cellular and network level, including theta and gamma
      oscillations in rodent hippocampal circuits. Little is known, however, about the
      contribution of I(h) to a prominent memory-related pattern of network activity
      called sharp-wave-ripple complexes (SPW-R). Here we report that pharmacological
      suppression of I(h) induces specific changes in SPW-R in mouse hippocampal slices
      depending on the specific drug used and the region analyzed. Spontaneous
      generation of the events was reduced by blocking I(h) whereas the amplitude was
      unaffected or increased. Interestingly, the superimposed ripple oscillations at
      ~200 Hz persisted with unchanged frequency, indicating that I(h) is not critical
      for generating this rhythmic pattern. Likewise, coupling between field
      oscillations and units was unchanged, showing unaltered recruitment of neurons
      into oscillating assemblies. Control experiments exclude a contribution of T-type
      calcium channels to the observed effects. Together, we report a specific
      contribution of hyperpolarization-activated cation currents to the generation of
      sharp waves in the hippocampus.

PMID- 23123921
TI  - Loss of survivin in neural precursor cells results in impaired long-term
      potentiation in the dentate gyrus and CA1-region.
AB  - In adult mammals, newborn neural precursor cells (NPCs) derived from either the
      subventricular zone (SVZ) or the subgranular zone (SGZ) migrate into the
      olfactory bulb and the dentate gyrus (DG), respectively, where some of them
      mature into excitatory and inhibitory neurons. There is increasing evidence that
      this neurogenesis process is important for some types of learning and synaptic
      plasticity and vice versa. Survivin, a member of the inhibitor-of-apoptosis
      protein (IAP) family, has been suggested to have a central role in the regulation
      of neurogenesis. The protein is abundantly expressed in nervous tissue during
      embryonic development while being restricted postnatally to proliferating and
      migrating NPCs in SVZ and SGZ. Here we examined adult Survivin(Camcre) mice with
      a conditional deletion of the survivin gene in embryonic neurogenic regions.
      Although the deletion of survivin had no effect on basic excitability in DG and
      CA1-region, there was a marked impairment of long-term potentiation (LTP) in
      these areas. Our data support a function of survivin in hippocampal synaptic
      plasticity and learning and underline the importance of adult brain neurogenesis
      for proper operation of the hippocampal tri-synaptic circuit and the
      physiological functions that depend on it.

PMID- 23123922
TI  - Photodermatoses in pigmented skin.
AB  - Photodermatoses are a group of skin diseases primarily caused by, or exacerbated
      by exposure to ultraviolet and or visible radiation. The effect of sunlight on
      skin depends on a number of factors including skin colour, skin phototype and the
      content and type of melanin in the skin. There are only a few studies describing
      photodermatoses in populations with dark skin. A PubMed search was conducted to
      summarize currently available information on differences in biology of melanin in
      dark and light skin and photodermatoses in dark skin. Dark skin is characterised
      by higher content of melanin, higher eumelanin to pheomelanin ratio, lower
      tyrosinase activity, and more effective distribution of melanin for protection
      against ultraviolet light. Photodermatoses are common in dark skinned patients
      with some variation in the spectrum of photodermatoses. Polymorphous light
      eruption (PMLE) is the commonest, followed by chronic actinic dermatitis. Pin
      point papular and lichenoid variants of PMLE and actinic lichen planus are more
      frequent in dark skin whereas actinic prurigo, solar urticaria and hydroa
      vacciniforme are uncommon. Photodermatoses are common in dark skinned patients
      despite better natural photoprotection. It is proposed that lichenoid
      photodermatoses may be added to the classification of photodermatoses in dark
      skin.

PMID- 23123924
TI  - The surprising link between hair curlers and drug discovery.

PMID- 23123923
TI  - Reactive astrocytes contribute to increased epileptic susceptibility induced by
      subthreshold dose of pilocarpine.
AB  - Seizures may influence epileptogenesis, but it is not yet clearly established
      whether subthreshold stimulations that are not sufficient to induce visible
      behavioral seizures change epileptic susceptibility, and the possible underlying
      mechanisms have not been completely understood. We assessed the susceptibility to
      epilepsy after subthreshold dose of pilocarpine, as well as glial fibrillary
      acidic protein (GFAP) expression using immunohistochemistry. An increase in the
      susceptibility to pentylenetetrazole (PTZ)-induced seizures was observed in rats
      previously subjected to subthreshold dose of pilocarpine. The immunoreactivity of
      GFAP was also increased, indicating that astrocytes became reactive in some brain
      subfields. The increased epileptic susceptibility was significantly reduced by L
      alpha-aminoadipic acid (L-AAA), an inhibitor of astrocytic function. Our results
      suggest that subthreshold stimulation may increase the susceptibility to
      subsequent development of epilepsy, and reactive astrocytes might be an important
      contributor to this process. Adequate inhibition of astrocytic function may be a
      potential preventive approach against epileptogenesis.

PMID- 23123915
TI  - Comparison of hematologic measurements between local and central laboratories:
      data from the BABY HUG trial.
AB  - OBJECTIVES: To investigate the concordance of blood count indices measured
      locally and at a central laboratory. DESIGN AND METHODS: In a multi-center
      clinical trial of hydroxyurea therapy in infants with sickle cell anemia (BABY
      HUG), the concordance between blood count indices measured locally and at a
      central laboratory was investigated. RESULTS: Local laboratory measurements of
      neutrophil and monocyte counts were significantly higher (44% and 37%,
      respectively) compared to the central measurements (p<0.0001), and mean
      corpuscular volume (MCV) was higher centrally. CONCLUSION: Overnight shipping
      with processing delay causes spurious reductions in absolute neutrophil count
      (ANC) and absolute monocyte count (AMC) that may result in incorrect monitoring
      decisions in multicenter clinical trials.

PMID- 23123925
TI  - Difference in time-course of improvement in asthma control measures between
      budesonide and budesonide/formoterol.
AB  - Combinations of inhaled corticosteroids (ICS) and inhaled long-acting beta(2)
      agonists (LABA) have become widely used for the initiation of maintenance
      treatment for asthma. However, it has not been fully elucidated whether ICS/LABA
      alters the time-course of different control outcome measures in steroid-naive
      patients with asthma compared to the treatment with ICS alone. We compared the
      time-response in Asthma Control Questionnaire (ACQ), forced expiratory volume in
      1 s (FEV1), exhaled nitric oxide fraction (FE(NO)), and airway responsiveness to
      methacholine (PD(200)) between budesonide (BUD) and budesonide/formoterol
      (BUD/FM). BUD/FM therapy significantly improved the ACQ score at week 2 and week
      4 (p < 0.01 and p < 0.05), and increased FEV1 and the methacholine threshold at
      week 8 and week 24 (all p < 0.05) compared to BUD alone. A logistic function
      model showed that the BUD/FM combination significantly improved ACQ, FEV1, FE(NO)
      and PD(200) at a faster rate than BUD over 24 weeks (p < 0.001 for ACQ, FEV1,
      PD(200), and p < 0.05 for FE(NO), z-test). A significant variance in the time
      response was also found in the outcomes of the two treatment groups (FE(NO) and
      ACQ > FEV1 and PD(200), p < 0.001, z-test). The present study provides evidence
      that ICS/LABA combination therapy results in a more rapid improvement in asthma
      symptoms, lung function, and airway inflammation compared to ICS monotherapy in
      steroid-naive patients with asthma.

PMID- 23123926
TI  - Retinoblastoma external beam photon irradiation with a special 'D'-shaped
      collimator: a comparison between measurements, Monte Carlo simulation and a
      treatment planning system calculation.
AB  - Retinoblastoma is the most common eye tumour in childhood. According to the
      available long-term data, the best outcome regarding tumour control and visual
      function has been reached by external beam radiotherapy. The benefits of the
      treatment are, however, jeopardized by a high incidence of radiation-induced
      secondary malignancies and the fact that irradiated bones grow asymmetrically. In
      order to better exploit the advantages of external beam radiotherapy, it is
      necessary to improve current techniques by reducing the irradiated volume and
      minimizing the dose to the facial bones. To this end, dose measurements and
      simulated data in a water phantom are essential. A Varian Clinac 2100 C/D
      operating at 6 MV is used in conjunction with a dedicated collimator for the
      retinoblastoma treatment. This collimator conforms a 'D'-shaped off-axis field
      whose irradiated area can be either 5.2 or 3.1 cm(2). Depth dose distributions
      and lateral profiles were experimentally measured. Experimental results were
      compared with Monte Carlo simulations' run with the penelope code and with
      calculations performed with the analytical anisotropic algorithm implemented in
      the Eclipse treatment planning system using the gamma test. penelope simulations
      agree reasonably well with the experimental data with discrepancies in the dose
      profiles less than 3 mm of distance to agreement and 3% of dose. Discrepancies
      between the results found with the analytical anisotropic algorithm and the
      experimental data reach 3 mm and 6%. Although the discrepancies between the
      results obtained with the analytical anisotropic algorithm and the experimental
      data are notable, it is possible to consider this algorithm for routine treatment
      planning of retinoblastoma patients, provided the limitations of the algorithm
      are known and taken into account by the medical physicist and the clinician.
      Monte Carlo simulation is essential for knowing these limitations. Monte Carlo
      simulation is required for optimizing the treatment technique and the dedicated
      collimator.

PMID- 23123920
TI  - Stress and the developing adolescent brain.
AB  - Adolescence is a time of continued brain maturation, particularly in limbic and
      cortical regions, which undoubtedly plays a role in the physiological and
      emotional changes coincident with adolescence. An emerging line of research has
      indicated that stressors experienced during this crucial developmental stage may
      affect the trajectory of this neural maturation and contribute to the increase in
      psychological morbidities, such as anxiety and depression, often observed during
      adolescence. In this review, we discuss the short- and long-term effects of
      periadolescent stress exposure on the structure and function of the brain. More
      specifically, we examine how stress at prepubertal and early adolescent stages of
      development affects the morphological plasticity of limbic and cortical brain
      regions, as well as the enduring effects of adolescent stress exposure on these
      brain regions in adulthood. We suggest that, due to a number of converging
      factors during this period of maturation, the adolescent brain may be
      particularly sensitive to stress-induced neurobehavioral dysfunctions with
      important consequences on an individual's immediate and long-term health and well
      being.

PMID- 23123927
TI  - EU-AIMS: a boost to autism research.
AB  - A ?30 million initiative bringing together academic centres, industry, charities
      and patient groups provides an unprecedented opportunity for translational
      research on autism.

PMID- 23123928
TI  - Cholesterol-lowering blockbuster candidates speed into Phase III trials.

PMID- 23123929
TI  - New class of kinase inhibitors poised to join the anticancer arsenal.

PMID- 23123931
TI  - Deal watch: 'Big data' deal for diabetes clinical trial modelling.

PMID- 23123932
TI  - Deal watch: J&J and Genmab deal to push forward CD38 as a blood cancer target.

PMID- 23123934
TI  - Garry Neil. Interview by Asher Mullard.

PMID- 23123935
TI  - Alzheimer's Disease: JNK3 as new target in AD?

PMID- 23123937
TI  - G protein-coupled receptors: Pioneering peptide GPCR structure determined.

PMID- 23123943
TI  - Identification of Bangladeshi domestic cats with GM1 gangliosidosis caused by the
      c.1448G>C mutation of the feline GLB1 gene: case study.
AB  - GM1 gangliosidosis is a fatal, progressive neurodegenerative lysosomal storage
      disease caused by mutations in the beta-galactosidase (GLB1) gene. In feline GM1
      gangliosidosis, a pathogenic mutation (c.1448G>C) in the feline GLB1 gene was
      identified in Siamese cats in the United States and Japan and in Korat cats in
      Western countries. The present study found the homozygous c.1448G>C mutation in 2
      apparent littermate native kittens in Bangladesh that were exhibiting
      neurological signs. This is the first identification of GM1 gangliosidosis in
      native domestic cats in Southeast Asia. This pathogenic mutation seems to have
      been present in the domestic cat population in the Siamese region and may have
      been transferred to pure breeds such as Siamese and Korat cats originating in
      this region.

PMID- 23123944
TI  - A spayed female cat with squamous cell carcinoma in the uterine remnant.
AB  - A 7-year-old spayed female domestic short-haired cat presented with dysuria and
      hematuria that had been unresponsive to medical therapy. Imaging tests such as
      ultrasonography, urethrocystography and computed tomography revealed a pelvic
      mass compressing the urethra. Based on histological examination of the mass
      following surgical resection, the cat was diagnosed squamous cell carcinoma (SCC)
      derived from the uterine remnant. After surgery, dysuria was resolved, but on
      instead, urine and fecal incontinence were observed. Then, about four months
      after surgery, recurrence of the mass and the symptoms was observed.
      Consequently, the cat was ultimately euthanized. This is the first report of SCC
      arising from the uterine remnant in a spayed female cat.

PMID- 23123946
TI  - Correlated recombination and annealing of point defects in dilute and
      concentrated Fe-Cr alloys.
AB  - In this work, we present a comprehensive combined modelling approach to study the
      annealing of lattice defects in dilute and concentrated metallic alloys. The
      developed approach consists in the combination of molecular dynamics, atomistic
      kinetic Monte Carlo (AKMC) and mean field rate theory methods, linked at
      appropriate time and space scales. For the first time, the AKMC tool has been
      designed to model the evolution of point defects (both vacancies and self
      interstitial atoms) in random concentrated alloys, taking into account the
      influence of lattice distortion on the local migration energy barrier due to the
      mutual interaction of point defects and solutes. Good accuracy and outstanding
      speed of calculations has been achieved by introducing the artificial neural
      network regression as an engine of the AKMC applied to calculate migration
      barriers for mobile defects. The developed method was applied to study correlated
      recombination in bcc Fe and random Fe-Cr alloys, aiming at the reproduction of a
      set of experimental studies after electron irradiation. The obtained results
      agree well with the available experimental data, implying that the developed
      modelling procedure correctly captures the undergoing physical process.

PMID- 23123941
TI  - Drug repositioning for Alzheimer's disease.
AB  - Existing drugs for Alzheimer's disease provide symptomatic benefit for up to 12
      months, but there are no approved disease-modifying therapies. Given the recent
      failures of various novel disease-modifying therapies in clinical trials, a
      complementary strategy based on repositioning drugs that are approved for other
      indications could be attractive. Indeed, a substantial body of preclinical work
      indicates that several classes of such drugs have potentially beneficial effects
      on Alzheimer's-like brain pathology, and for some drugs the evidence is also
      supported by epidemiological data or preliminary clinical trials. Here, we
      present a formal consensus evaluation of these opportunities, based on a
      systematic review of published literature. We highlight several compounds for
      which sufficient evidence is available to encourage further investigation to
      clarify an optimal dose and consider progression to clinical trials in patients
      with Alzheimer's disease.

PMID- 23123948
TI  - Shifting dying trajectories: integrating self-management and palliative care.

PMID- 23123945
TI  - Repeated exposure to the herbicide atrazine alters locomotor activity and the
      nigrostriatal dopaminergic system of the albino rat.
AB  - Atrazine (ATR) is used as a pre- and post-emergent herbicide; although banned in
      several countries of the European Community, it is still used extensively around
      the world. A recent study in rats has shown that chronic, daily exposure to 10 mg
      ATR/kg BW causes hyperactivity, disrupts motor coordination and learning of
      behavioral tasks, and decreases dopamine levels in the brain. In order to
      evaluate the short-term effect of ATR exposure on locomotor activity, monoamine
      markers, and antioxidants, adult male Sprague-Dawley rats received six IP
      injections of 100 mg ATR/kg BW or vehicle over two weeks. After every ATR
      injection we found hypoactivity that lasted up to five days, and it was
      accompanied by reductions in levels of striatal DA, DOPAC, and HVA without any
      alteration in the striatal expression of the mRNAs for Mn-SOD, Trx-1, DAR-D(1),
      or DAR-D(2). In contrast, in the nucleus accumbens no changes in monoamine
      markers were observed, and a down-regulation of Trx-1 expression was detected
      shortly after the ATR treatment. Moreover, in the ventral midbrain, we found that
      ATR induced a down-regulation of mRNA for Th and DAT, but it increased VMAT2 mRNA
      expression. Decreases of monoamine levels and of locomotor activity disappeared
      three months after ATR treatment; however, an amphetamine challenge (1 mg/kg)
      given two months after the ATR treatment resulted in a significant stimulation in
      the exposed group, revealing hidden effects of ATR on dopaminergic systems. These
      results indicate that ATR exposure differentially modifies the dopaminergic
      systems, and these modifications may underlie the behavioral changes observed.

PMID- 23123949
TI  - Giving people choice at the end of life.

PMID- 23123947
TI  - The use and role of open source software applications in public and not-for
      profit hospitals in the United States.
AB  - BACKGROUND: The potential cost savings and customizability of open source
      software (OSS) may be particularly attractive for hospitals. However, numerous
      health-care-specific OSS applications exist, the adoption of OSS health
      information technology (HIT) applications is not widespread in the United States.
      PURPOSE: This disconnect between the availability of promising software and low
      adoption raises the basic question: If OSS HIT is so advantageous, why are more
      health care organizations not using it? METHODOLOGY: We interviewed the chief
      information officer, or equivalent position, at 17 not-for-profit and public
      hospitals across the United States. Through targeted recruitment, our sample
      included nine hospitals using OSS HIT and eight hospitals not using OSS HIT. The
      open-ended interview questions were guided by domains included in the fit
      viability theory, an organizational-level innovation adoption framework, and
      those suggested by a review of the literature. Transcripts were analyzed using an
      inductive and comparative approach, which involved an open coding for relevant
      themes. FINDINGS: Interviews described the state of OSS use in hospitals.
      Specifically, general OSS applications were widely used by IT professionals. In
      addition, hospitals using OSS HIT still relied heavily on vendor support. In
      terms of why decisions arose to use OSS HIT, several hospitals using OSS HIT
      noted the cost advantages. In contrast, hospitals avoiding OSS HIT were clear,
      OSS as a class did not fit with clinical work and posed too much risk. PRACTICE
      IMPLICATIONS: Perceptions of OSS HIT ranged from enthusiastic embracement to
      resigned adoption, to refusal, to abandonment. Some organizations were achieving
      success with their OSS HIT choices, but they still relied on vendors for
      significant support. The decision to adopt OSS HIT was not uniform but contingent
      upon views of the risk posed by the technology, economic factors, and the
      hospital's existing capabilities.

PMID- 23123942
TI  - The spliceosome as a target of novel antitumour drugs.
AB  - Several bacterial fermentation products and their synthetic derivatives display
      antitumour activities and bind tightly to components of the spliceosome, which is
      the complex molecular machinery involved in the removal of introns from mRNA
      precursors in eukaryotic cells. The drugs alter gene expression, including
      alternative splicing, of genes that are important for cancer progression. A
      flurry of recent reports has revealed that genes encoding splicing factors,
      including the drug target splicing factor 3B subunit 1 (SF3B1), are among the
      most highly mutated in various haematological malignancies such as chronic
      lymphocytic leukaemia and myelodysplastic syndromes. These observations highlight
      the role of splicing factors in cancer and suggest that an understanding of the
      molecular effects of drugs targeting these proteins could open new perspectives
      for studies of the spliceosome and its role in cancer progression, and for the
      development of novel antitumour therapies.

PMID- 23123950
TI  - Neuropathic pain management  in children.
AB  - There are difficulties in assessing, managing, and evaluating neuropathic pain in
      dying children, particularly those with neurological impairment. Neuropathic pain
      in children often presents differently to how it presents in the adult
      population. Comprehensive assessment as well as pharmacological and non
      pharmacological interventions are crucial to its successful management and
      frequently require input from an interdisciplinary team. Notwithstanding the need
      for further research, this paper brings together research papers, reviews, and
      clinical guidelines to present an exploration of existing evidence regarding care
      for children with neuropathic pain and their families.

PMID- 23123951
TI  - Evaluation of the Dignity Care Pathway for community nurses caring for people at
      the end of life.
AB  - BACKGROUND: People nearing the end of life fear loss of dignity, and a central
      tenet of palliative care is to help people die with dignity. The Dignity Care
      Pathway (DCP) is an intervention based on the Chochinov theoretical model of
      dignity care. It has four sections: a manual, a Patient Dignity Inventory,
      reflective questions, and care actions. METHOD: The feasibility and acceptability
      of the DCP were evaluated using a qualitative design with a purposive sample of
      community nurses. Data was collected from April to October 2010 using in-depth
      interviews, reflective diaries, and case studies and then analysed using
      framework analysis. RESULTS: The DCP was acceptable to the community nurses,
      helped them identify when patients were at the end of life, identified patients'
      key concerns, and aided nurses in providing holistic end-of-life care. It
      requires the nurse to have excellent communication skills. Some of the nurses
      found it hard to initiate a conversation on dignity-conserving care. CONCLUSION:
      The DCP helps nurses to deliver individualised care and psychological care, which
      has previously been identified as a difficult area for community nurses. All of
      the nurses wished to continue to use the DCP and would recommend it to others.

PMID- 23123952
TI  - Family carers' experiences of support at the end of life: carers' and health
      professionals' views.
AB  - This paper reports findings from an exploratory qualitative study concerning end
      of-life support for family carers in an acute ward setting. The participants
      included bereaved carers of patients who had died in an acute ward or hospice, as
      well as health professionals. Interviews and focus groups were used to collect
      data. The study provides insights into the perceptions and needs of carers at the
      end of life and the challenges these present for nursing staff in an acute ward.
      This paper focuses on one key theme incorporating issues around communication
      between family and nursing staff and the availability of practical facilities. It
      provides information that may be beneficial to hospital staff who work in acute
      areas where there is an expectation they will support carers around the time of
      death.

PMID- 23123953
TI  - 'Making sense': nurses' experiences  of changing practice in caring for dying
      patients in New Zealand.
AB  - AIM: To explore nurses' experiences of a top-down change that involved the
      introduction of the Liverpool Care Pathway for the Dying Patient (LCP). METHODS:
      Using a qualitative design, two focus groups were conducted with a total of ten
      nurses and five semi-structured individual interviews were conducted with senior
      nurse managers. FINDINGS: The nurses viewed their experience with the LCP
      positively, highlighting an improvement in their knowledge base regarding care of
      the dying. 'Making sense' was a key theme that reflected how the nurses attempted
      to manage the impact of the change on their own practice and on the nursing team.
      CONCLUSION: Organisations need to invest skilled manpower, time, and resources
      into supporting nurses in their transitions. The benefits of such investment are
      an increased likelihood of implementing evidence-based care and sustained
      practice and organisational change. For patients and their families and friends
      this investment will result in tangible improvements in the delivery of treatment
      and care at a time in their lives when they are most vulnerable.

PMID- 23123954
TI  - Hospice nurses' perceptions of caring for patients with a non-malignant
      diagnosis: a single-site case study.
AB  - In the early stages of its development in the UK, palliative care focused almost
      exclusively on the care of patients with cancer, with efforts concentrated on
      relieving distressing physical symptoms in the last few weeks of life-often
      referred to as terminal care. It is increasingly expanding to include non
      malignant conditions, but is still predominantly accessed by cancer patients.
      This paper presents findings from a small-scale qualitative study into nurses'
      experiences of providing hospice care for patients with a non-malignant
      diagnosis. Two focus groups were conducted with nurses in one established UK
      hospice. The results highlight the importance of timely educational preparation,
      the need for proactive thinking regarding the shifting medical profiles of health
      care in the UK, and the need for hospice managers to critically consider existing
      infrastructures (including supervision and support) in anticipation of diverse
      patient populations. The paper also reiterates that collaboration remains the key
      to effective support.

PMID- 23123956
TI  - Hypothalamic melanin-concentrating hormone projections to the septo-hippocampal
      complex in the rat.
AB  - Melanin-concentrating hormone (MCH) and neuropeptide glutamic acid-isoleucine
      (NEI) are expressed in neurons that are located mainly in the hypothalamus and
      project widely throughout the rat central nervous system. One of the main targets
      of melanin-concentrating hormone is the hippocampal formation, although the exact
      origin of the projections is unknown. By using injections of the retrograde
      tracer True Blue into the hippocampus, together with immunohistochemical
      analysis, we observed retrogradely labeled melanin-concentrating hormone
      containing neurons in the lateral hypothalamic area, incerto-hypothalamic area,
      perifornical area, the periventricular nucleus of the hypothalamus, and in the
      internuclear area (between the dorsomedial and ventromedial nuclei of the
      hypothalamus), as well as a few retrogradely labeled and melanin-concentrating
      hormone-immunoreactive cells in the supramammillary nucleus. The afferents from
      the lateral hypothalamic area were confirmed using injection of the anterograde
      tracer biotinylated dextran amine, which enabled us to use histochemical analysis
      in order to visualize fibers and terminals in the hippocampal formation. In the
      medial septal nucleus, we found cholinergic neurons that are also putatively
      innervated by melanin-concentrating hormone immunoreactive fibers and project to
      the hippocampal formation. Finally, using two different protocols for
      immunoperoxidase, we were able to show GABAergic basket cells presumably
      innervated by melanin-concentrating hormone-immunoreactive fibers in the
      hippocampal formation. On the basis of the data collected herein, we hypothesize
      that the MCH/NEI projections from hypothalamic nuclei participate in spatial
      memory and learning through direct and indirect pathways. These pathways would
      enable the animal to organize its exploratory behavior during foraging.

PMID- 23123957
TI  - Purification and characterization of an antioxidant glycoprotein from the
      hydrolysate of Mustelus griseus.
AB  - An antioxidant glycoprotein (Fraction AIV-2) with molecular weight of 27.2 kDa
      was purified from the ethanol-soluble protein hydrolysate of Mustelus griseus
      muscle. The 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity of
      Fraction AIV-2 reached up to 96.73+/-2.33% and was higher than that of ascorbic
      acid at the concentration of 5.0mg/mL. Total protein and carbohydrate contents of
      Fraction AIV-2 were 62.65+/-0.63% and 33.49+/-1.60%, respectively. Seventeen
      amino acids were identified in Fraction AIV-2, most of which are serine. GC-MS
      analysis showed that Fraction AIV-2 was composed of fucose, arabinose, galactose,
      glucose and mannose with the ratio of 1.00:1.53:7.27:9.07:2.09. The FT-IR
      spectrum of Fraction AIV-2 showed typical characteristics of polysaccharide and
      protein. For Fraction AIV-2, the changes of ultraviolet absorption curve, amino
      acid composition after the beta-elimination reaction and its deglycosylation with
      the treatment of N-glycosidase F suggested that both O-glycosidic and N
      glycosidic bonds were involved in the polysaccharide and protein moieties.

PMID- 23123958
TI  - Monitoring protein denaturation using thermal conductivity probe.
AB  - We propose a method for probing denaturation of proteins by measuring the thermal
      conductivity of the solution. We use the three-omega method with a
      microfabricated ac thermal sensor to measure the thermal conductivity of
      lysozyme, beta-lactoglobulin, and bovine serum albumin protein solutions over a
      range of temperature and pH. Results suggest that conformation transformation of
      the protein during denaturation changes the thermal network in protein solutions
      and thus changes the thermal conductivity for all the tested proteins. The
      proposed method of denaturation monitoring requires much simpler experimental
      setup than conventional methods such as differential scanning calorimetry and
      circular dichroism detection. We also demonstrate that the proposed analytical
      technique can detect the protein denaturation in real time. Consequently, it is
      expected to be useful in lab-on-a-chip (LoC) applications as the probe can be
      easily miniaturized for integration into LoC devices and allows real-time
      analysis.

PMID- 23123959
TI  - Effect of fish collagen modification on its thermal and rheological properties.
AB  - This report describes the effects of different methods of silver carp collagen
      crosslinking on its properties, particularly their thermal, mechanical
      viscoelastic and biological behavior. Enzymatic analyses and determination of the
      degree of crosslinking showed the stabilizing effect of both dehydrothermal (DHT)
      and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC)/N-hydroxysuccinimide
      (NHS) treatments on fish collagen. The results of the thermal (DSC) measurements
      demonstrated that collagen crosslinked by EDC/NHS ensured a high thermal
      stability compared with collagen crosslinked dehydrothermally. The denaturation
      temperature (T(d)) of unmodified collagen samples increased from 77 to 80 degrees
      C and 88 degrees C for DHT- and EDC/NHS-treated collagen, respectively. The
      influence of DHT or EDC/NHS crosslinking on the viscoelastic behavior of fish
      collagen was elaborated by a shift of the tan delta(max) peak toward higher
      temperatures resulting in higher thermostability of the modified collagen
      samples.

PMID- 23123960
TI  - Antibacterial multilayer films fabricated by LBL immobilizing lysozyme and HTCC
      on nanofibrous mats.
AB  - Cellulose acetate nanofibrous mats were prepared by electrospunning technique.
      Positively charged and negatively charged composites were alternately deposited
      on negatively charged CA mats via layer-by-layer self-assembly technique. The
      morphology and inhibition rate of samples were investigated by regulating number
      of deposition bilayers and composition of outermost layer. Field emission
      scanning electron microscopy images indicated that the average diameter of fibers
      was increased with increasing the number of coating bilayers. Additionally, the
      catalytic activity of immobilized LY was measured and results showed "layer-by
      layer alternative oscillation" phenomenon. The results of antibacterial assay
      indicated that (LY-HTCC/ALG)(10.5) films coating had the best inhibitory effect.

PMID- 23123961
TI  - The zebrafish homologue of Parkinson's disease ATP13A2 is essential for embryonic
      survival.
AB  - ATP13A2 is a lysosome-specific transmembrane ATPase protein of unknown function.
      This protein was initially linked to Kufor-Rakeb syndrome where it is absent or
      mutated. More recently, point mutations in ATP13A2 were linked to familial cases
      of Parkinson's disease. Zebrafish is commonly used as a vertebrate model for the
      study of different neurodegenerative diseases and has homologues of several
      Parkinson's disease associated proteins. Here, we describe for the first time the
      zebrafish homologue of human ATP13A2, demonstrating the homology between the
      protein sequences, which supports a conserved biological role. Furthermore, the
      spatial pattern of protein expression was studied and the lethality of the
      knockdown of ATP13A2 suggests it plays a crucial role during embryonic
      development. Our findings bring new insight into the biology of ATP13A2 and open
      novel opportunities for its study using zebrafish as a model organism.

PMID- 23123962
TI  - Inverse opal tungsten trioxide films with mesoporous skeletons: synthesis and
      photoelectrochemical responses.
AB  - Inverse opal structured tungsten trioxide (WO(3)) films with mesoporous
      morphology were prepared using self-assembled polystyrene (PS) colloid as an
      organic template and by addition of polyethyleneglycol (PEG) to a precursor as an
      organic surfactant. The photoelectrochemical properties of these films were
      investigated. By adjusting the tungsten to PEG weight ratio in the precursor, an
      inverse opaline WO(3) film with a nano-particular skeleton and increased specific
      surface area was constructed. The unique morphology of this film led to enhanced
      photoelectrochemical catalytic responses under UV-Visible 1-sun illumination.

PMID- 23123963
TI  - The contactin RIG-6 mediates neuronal and non-neuronal cell migration in
      Caenorhabditis elegans.
AB  - Cell adhesion molecules of the Immunoglobulin Superfamily (IgCAMs) are key
      factors in nervous system formation. The contactin subgroup of IgCAMs consists of
      GPI-anchored glycoproteins implicated in axon outgrowth, guidance, fasciculation
      and neuronal differentiation. The mechanism by which contactins facilitate
      neuronal development is not understood. To gain insight into the function of
      contactins, we characterized RIG-6, the sole contactin of Caenorhabditis elegans.
      We show that the contactin RIG-6 is involved in excretory cell (EC) tubular
      elongation. We also show that RIG-6 mediates axon outgrowth and guidance along
      both the anterior-posterior and dorso-ventral axis, during C. elegans
      development. We find that optimal RIG-6 expression is critical for accurate
      mechanosensory neuron axon elongation and ventral nerve cord architecture. In
      addition, our data suggest that the cytoplasmic UNC-53/NAV2 proteins may
      contribute to relay signaling via contactins.

PMID- 23123964
TI  - The Retinoblastoma pathway regulates stem cell proliferation in freshwater
      planarians.
AB  - Freshwater planarians are flatworms of the Lophotrochozoan superphylum and are
      well known for their regenerative abilities, which rely on a large population of
      pluripotent adult stem cells. However, the mechanisms by which planarians
      maintain a precise population of adult stem cells while balancing proliferation
      and cell death, remain to be elucidated. Here we have identified, characterized,
      and functionally tested the core Retinoblastoma (Rb) pathway components in
      planarian adult stem cell biology. The Rb pathway is an ancient and conserved
      mechanism of proliferation control from plants to animals and is composed of
      three core components: an Rb protein, and a transcription factor heterodimer of
      E2F and DP proteins. Although the planarian genome contains all components of the
      Rb pathway, we found that they have undergone gene loss from the ancestral state,
      similar to other species in their phylum. The single Rb homolog (Smed-Rb) was
      highly expressed in planarian stem cells and was required for stem cell
      maintenance, similar to the Rb-homologs p107 and p130 in vertebrates. We show
      that planarians and their phylum have undergone the most severe reduction in E2F
      genes observed thus far, and the single remaining E2F was predicted to be a
      repressive-type E2F (Smed-E2F4-1). Knockdown of either Smed-E2F4-1 or its
      dimerization partner Dp (Smed-Dp) by RNAi resulted in temporary hyper
      proliferation. Finally, we showed that known Rb-interacting genes in other
      systems, histone deacetylase 1 and cyclinD (Smed-HDAC1; Smed-cycD), were similar
      to Rb in expression and phenotypes when knocked down by RNAi, suggesting that
      these established interactions with Rb may also be conserved in planarians.
      Together, these results showed that planarians use the conserved components of
      the Rb tumor suppressor pathway to control proliferation and cell survival.

PMID- 23123966
TI  - Depletion of Suds3 reveals an essential role in early lineage specification.
AB  - Preimplantation development culminates with the emergence of three distinct
      populations: the inner cell mass, primitive endoderm and trophectoderm. Here, we
      define the mechanisms underlying the requirement of Suds3 in pre/peri
      implantation development. Suds3 knockdown blastocysts exhibit a failure of both
      trophectoderm proliferation as well as a conspicuous lack of primitive endoderm.
      Expression of essential lineage factors Nanog, Sox2, Cdx2, Eomes, Elf5 and Sox17
      are severely reduced in the absence of Suds3. Importantly, we document deficient
      FGF4/ERK signaling and show that exogenous FGF4 rescues primitive endoderm
      formation and trophectoderm proliferation in Suds3 knockdown blastocysts. We also
      show that Hdac1 knockdown reduces Sox2/FGF4/ERK signaling in blastocysts.
      Collectively, these data define a role for Suds3 in activation of FGF4/ERK
      signaling and determine an essential molecular role of Suds3/Sin3/HDAC complexes
      in lineage specification in vivo.

PMID- 23123965
TI  - Negative regulation of Shh levels by Kras and Fgfr2 during hair follicle
      development.
AB  - Activating mutations in the KRAS oncogene are associated with three related human
      syndromes, which vary in hair and skin phenotypes depending on the involved
      allele. How variations in RAS signals are interpreted during hair and skin
      development is unknown. In this study, we investigated the developmental and
      transcriptional response of skin and hair to changes in RAS activity, using mouse
      genetic models and microarray analysis. While activation of Kras (Kras(G12D)) in
      the skin had strong effects on hair growth and hair shape, steady state changes
      in downstream RAS/MAPK effectors were subtle and detected only by transcriptional
      responses. To model the transcriptional response of multiple developmental
      pathways to active RAS, the effects of growth factor stimulation were studied in
      skin explants. Here FGF acutely suppressed Shh transcription within 90 min but
      had significantly less effect on Eda, WNT, Notch or BMP pathways. Furthermore, in
      vivo Fgfr2 loss-of-function in the ectoderm caused derepression of Shh, revealing
      a role for FGF in Shh regulation in the hair follicle. These studies define both
      dosage sensitive effects of RAS signaling on hair morphogenesis and reveal acute
      mechanisms for fine-tuning Shh levels in the hair follicle.

PMID- 23123968
TI  - Determinants of plasma copeptin: a systematic investigation in a pediatric
      mechanical ventilation model.
AB  - Copeptin, the C-terminal part of the arginine vasopressin precursor peptide,
      holds promise as a diagnostic and prognostic plasma biomarker in various acute
      clinical conditions. Factors influencing copeptin response in the critical care
      setting are only partially established and have not been investigated
      systematically. Using an in vivo infant ventilation model (Wistar rats, 14 days
      old), we studied the influence of commonly occurring stressors in critically ill
      children. In unstressed ventilated rats basal median copeptin concentration was
      22pmol/L. In response to respiratory alkalosis copeptin increased 5-fold, while
      exposure to hypoxemia, high PEEP, hemorrhage, and psycho-emotional stress
      produced a more than 10-fold increase. Additionally, we did not find a direct
      association between copeptin and acidosis, hypercapnia, and hyperthermia.
      Clinicians working in the acute critical care setting should be aware of factors
      influencing copeptin plasma concentrations. Moreover, our results do have
      implications for animal studies in the field of stress research.

PMID- 23123967
TI  - Expression and function of cell adhesion molecules during neural crest migration.
AB  - Neural crest cells are highly migratory cells that give rise to many derivatives
      including peripheral ganglia, craniofacial structures and melanocytes. Neural
      crest cells migrate along defined pathways to their target sites, interacting
      with each other and their environment as they migrate. Cell adhesion molecules
      are critical during this process. In this review we discuss the expression and
      function of cell adhesion molecules during the process of neural crest migration,
      in particular cadherins, integrins, members of the immunoglobulin superfamily of
      cell adhesion molecules, and the proteolytic enzymes that cleave these cell
      adhesion molecules. The expression and function of these cell adhesion molecules
      and proteases are compared across neural crest emigrating from different axial
      levels, and across different species of vertebrates.

PMID- 23123969
TI  - Effects of breath holding at low and high lung volumes on amount of exhaled
      particles.
AB  - Exhaled breath contains particles originating from the respiratory tract lining
      fluid. The particles are thought to be generated during inhalation, by reopening
      of airways closed in the preceding expiration. The aim here was to explore
      processes that control exhaled particle concentrations. The results show that 5
      and 10s breath holding at residual volume increased the median concentration of
      particles in exhaled air by 63% and 110%, respectively, averaged over 10
      subjects. An increasing number of closed airways, developing on a timescale of
      seconds explains this behaviour. Breath holds of 5, 10 and 20s at total lung
      capacity decreased the concentration to 63%, 45% and 28% respectively, of the
      directly exhaled concentration. The decrease in particle concentration after
      breath holding at total lung capacity is caused by gravitational settling in the
      alveoli and associated bronchioles. The geometry employed here when modelling the
      deposition is however not satisfactory and ways of improving the description are
      discussed.

PMID- 23123970
TI  - Exploratory behaviour in the open field test adapted for larval zebrafish: impact
      of environmental complexity.
AB  - This study aimed to develop and characterize a novel (standard) open field test
      adapted for larval zebrafish. We also developed and characterized a variant of
      the same assay consisting of a colour-enriched open field; this was used to
      assess the impact of environmental complexity on patterns of exploratory
      behaviours as well to determine natural colour preference/avoidance. We report
      the following main findings: (1) zebrafish larvae display characteristic patterns
      of exploratory behaviours in the standard open field, such as thigmotaxis/centre
      avoidance; (2) environmental complexity (i.e. presence of colours) differentially
      affects patterns of exploratory behaviours and greatly attenuates natural zone
      preference; (3) larvae displayed the ability to discriminate colours. As reported
      previously in adult zebrafish, larvae showed avoidance towards blue and black;
      however, in contrast to the reported adult behaviour, larvae displayed avoidance
      towards red. Avoidance towards yellow and preference for green and orange are
      shown for the first time, (4) compared to standard open field tests, exposure to
      the colour-enriched open field resulted in an enhanced expression of anxiety-like
      behaviours. To conclude, we not only developed and adapted a traditional rodent
      behavioural assay that serves as a gold standard in preclinical drug screening,
      but we also provide a version of the same test that affords the possibility to
      investigate the impact of environmental stress on behaviour in larval zebrafish
      while representing the first test for assessment of natural colour
      preference/avoidance in larval zebrafish. In the future, these assays will
      improve preclinical drug screening methodologies towards the goal to uncover
      novel drugs. This article is part of a Special Issue entitled: insert SI title.

PMID- 23123971
TI  - Phase-resolved acoustic radiation force optical coherence elastography.
AB  - Many diseases involve changes in the biomechanical properties of tissue, and
      there is a close correlation between tissue elasticity and pathology. We report
      on the development of a phase-resolved acoustic radiation force optical coherence
      elastography method (ARF-OCE) to evaluate the elastic properties of tissue. This
      method utilizes chirped acoustic radiation force to produce excitation along the
      sample's axial direction, and it uses phase-resolved optical coherence tomography
      (OCT) to measure the vibration of the sample. Under 500-Hz square wave modulated
      ARF signal excitation, phase change maps of tissue mimicking phantoms are
      generated by the ARF-OCE method, and the resulting Young's modulus ratio is
      correlated with a standard compression test. The results verify that this
      technique could efficiently measure sample elastic properties accurately and
      quantitatively. Furthermore, a three-dimensional ARF-OCE image of the human
      atherosclerotic coronary artery is obtained. The result indicates that our
      dynamic phase-resolved ARF-OCE method can delineate tissues with different
      mechanical properties.

PMID- 23123972
TI  - Photoacoustic tomography through a whole adult human skull with a photon
      recycler.
AB  - ABSTRACT. Photoacoustic tomography (PAT) of the human brain is challenging due to
      the fact that the skull strongly absorbs and scatters light, and attenuates and
      distorts ultrasound as well. For the first time, we demonstrated the feasibility
      of PAT through a whole adult human skull. A photon recycler (PR) was built to
      increase light transmittance through the skull. Both a graphite target and a
      canine brain were imaged through the skull. Use of the PR was found to improve
      the photoacoustic signal-to-noise ratio by a factor of 2.4. In addition,
      subtraction of photoacoustic signals that arise from light absorption within the
      skull significantly improved the contrast of the target. Our results indicate
      that PAT can potentially be applied to in vivo human brain imaging.

PMID- 23123973
TI  - Open source software for electric field Monte Carlo simulation of coherent
      backscattering in biological media containing birefringence.
AB  - ABSTRACT. We present an open source electric field tracking Monte Carlo program
      to model backscattering in biological media containing birefringence, with
      computation of the coherent backscattering phenomenon as an example. These
      simulations enable the modeling of tissue scattering as a statistically
      homogeneous continuous random media under the Whittle-Matern model, which
      includes the Henyey-Greenstein phase function as a special case, or as a
      composition of discrete spherical scatterers under Mie theory. The calculation of
      the amplitude scattering matrix for the above two cases as well as the
      implementation of birefringence using the Jones N-matrix formalism is presented.
      For ease of operator use and data processing, our simulation incorporates a
      graphical user interface written in MATLAB to interact with the underlying C
      code. Additionally, an increase in computational speed is achieved through
      implementation of message passing interface and the semi-analytical approach.
      Finally, we provide demonstrations of the results of our simulation for purely
      scattering media and scattering media containing linear birefringence.

PMID- 23123974
TI  - Refractive index of solutions of human hemoglobin from the near-infrared to the
      ultraviolet range: Kramers-Kronig analysis.
AB  - Because direct measurements of the refractive index of hemoglobin over a large
      wavelength range are challenging, indirect methods deserve particular attention.
      Among them, the Kramers-Kronig relations are a powerful tool often used to derive
      the real part of a refractive index from its imaginary part. However, previous
      attempts to apply the relations to solutions of human hemoglobin have been
      somewhat controversial, resulting in disagreement between several studies. We
      show that this controversy can be resolved when careful attention is paid not
      only to the absorption of hemoglobin but also to the dispersion of the refractive
      index of the nonabsorbing solvent. We present a Kramers-Kroning analysis taking
      both contributions into account and compare the results with the data from
      several studies. Good agreement with experiments is found across the visible and
      parts of near-infrared and ultraviolet regions. These results reinstate the use
      of the Kramers-Kronig relations for hemoglobin solutions and provide an
      additional source of information about their refractive index.

PMID- 23123975
TI  - In vivo photoacoustic microscopy with 7.6-um axial resolution using a commercial
      125-MHz ultrasonic transducer.
AB  - Photoacoustic microscopy has achieved submicron lateral resolution, but its axial
      resolution is much lower. Here an axial resolution of 7.6 MUm, the highest axial
      resolution validated by experimental data, has been achieved by using a
      commercial 125 MHz ultrasonic transducer for signal detection followed by the
      Wiener deconvolution for signal processing. Limited by the working distance, the
      high-frequency ultrasonic transducer can penetrate 1.2 mm into biological tissue
      from the ultrasound detection side. At this depth, the signal-to-noise ratio
      decreases by 11 dB, and the axial resolution degrades by 36%. The new system was
      demonstrated in imaging melanoma cells ex vivo and mouse ears in vivo.

PMID- 23123978
TI  - Development of a repeated-dose liver micronucleus assay using adult rats (II):
      further investigation of 1,2-dimethylhydrazine and 2,6-diaminotoluene.
AB  - Detecting genotoxicity in the liver is considered an effective approach for
      predicting hepatocarcinogenicity, as many genotoxic chemicals in vivo may act as
      hepatocarcinogens in rodents. Here, a genotoxic rodent hepatocarcinogen, 1,2
      dimethylhydrazine dihydrochloride (1,2-DMH), and a genotoxic (Ames positive)
      noncarcinogen, 2,6-diaminotolunene (2,6-DAT), were administered orally to rats
      for up to 28 days, and liver samples were then examined in a repeated-dose liver
      micronucleus (MN) assay, and additionally tested in the bone marrow (BM) MN assay
      concurrently. We recently established a simple method to isolate hepatocytes
      without in situ liver perfusion procedures, and applied this method in the liver
      MN assay. As a result, 1,2-DMH increased the proportion of micronucleated
      hepatocytes in both a dose- and duration-dependent manner at relatively low-dose
      levels that are routinely used in repeated-dose toxicity studies. In contrast to
      1,2-DMH, 2,6-DAT did not have a detectable effect. In addition to these two
      chemicals, two genotoxic rodent hepatocarcinogens, diethylnitrosamine and 2,4
      diaminotoluene, which gave positive responses in the liver MN assay in our
      previous investigation [Narumi et al., Mutat. Res. 747 (2012) 234-239], were
      subjected to the BM MN assay and histopathological evaluation. All four test
      chemicals gave negative responses in the BM MN assay. Furthermore, the three
      hepatocarcinogens displayed hepatotoxicity, including hepatocellular hypertrophy
      and anisokaryosis, but no abnormal findings were observed in the liver of rats
      treated with 2,6-DAT. Taken together, the present results indicate that the liver
      MN assay is effective for predicting hepatocarcinogenicity and may be integrated
      into repeated-dose toxicity studies without disturbing routine examinations, such
      as histopathology. Furthermore, with repeat-dose treatment protocols, our
      findings indicate that the liver MN assay is superior to the BM MN assay for
      detecting genotoxic or carcinogenic chemicals in rats.

PMID- 23123977
TI  - Extraordinary GU-rich single-strand RNA identified from SARS coronavirus
      contributes an excessive innate immune response.
AB  - A dangerous cytokine storm occurs in the SARS involving in immune disorder, but
      many aspects of the pathogenetic mechanism remain obscure since its outbreak. To
      deeply reveal the interaction of host and SARS-CoV, based on the basic structural
      feature of pathogen-associated molecular pattern, we created a new bioinformatics
      method for searching potential pathogenic molecules and identified a set of SARS
      CoV specific GU-rich ssRNA fragments with a high-density distribution in the
      genome. In vitro experiments, the result showed the representative SARS-CoV
      ssRNAs had powerful immunostimulatory activities to induce considerable level of
      pro-inflammatory cytokine TNF-a, IL-6 and IL-12 release via the TLR7 and TLR8,
      almost 2-fold higher than the strong stimulatory ssRNA40 that was found
      previously from other virus. Moreover, SARS-CoV ssRNA was able to cause acute
      lung injury in mice with a high mortality rate in vivo experiment. It suggests
      that SARS-CoV specific GU-rich ssRNA plays a very important role in the cytokine
      storm associated with a dysregulation of the innate immunity. This study not only
      presents new evidence about the immunopathologic damage caused by overactive
      inflammation during the SARS-CoV infection, but also provides a useful clue for a
      new therapeutic strategy.

PMID- 23123980
TI  - Striving for improvement against all odds.

PMID- 23123976
TI  - Continuous sensing of tumor-targeted molecular probes with a vertical cavity
      surface emitting laser-based biosensor.
AB  - Molecular optical imaging is a widespread technique for interrogating molecular
      events in living subjects. However, current approaches preclude long-term,
      continuous measurements in awake, mobile subjects, a strategy crucial in several
      medical conditions. Consequently, we designed a novel, lightweight miniature
      biosensor for in vivo continuous optical sensing. The biosensor contains an
      enclosed vertical-cavity surface-emitting semiconductor laser and an adjacent
      pair of near-infrared optically filtered detectors. We employed two sensors (dual
      sensing) to simultaneously interrogate normal and diseased tumor sites. Having
      established the sensors are precise with phantom and in vivo studies, we
      performed dual, continuous sensing in tumor (human glioblastoma cells) bearing
      mice using the targeted molecular probe cRGD-Cy5.5, which targets alphaVbeta3
      cell surface integrins in both tumor neovasculature and tumor. The sensors
      capture the dynamic time-activity curve of the targeted molecular probe. The
      average tumor to background ratio after signal calibration for cRGD-Cy5.5
      injection is approximately 2.43+/-0.95 at 1 h and 3.64+/-1.38 at 2 h (N=5 mice),
      consistent with data obtained with a cooled charge coupled device camera. We
      conclude that our novel, portable, precise biosensor can be used to evaluate both
      kinetics and steady state levels of molecular probes in various disease
      applications.

PMID- 23123979
TI  - Exonuclease VII is involved in "reckless" DNA degradation in UV-irradiated
      Escherichia coli.
AB  - The recA mutants of Escherichia coli exhibit an abnormal DNA degradation that
      starts at sites of double-strand DNA breaks (DSBs), and is mediated by RecBCD
      exonuclease (ExoV). This "reckless" DNA degradation occurs spontaneously in
      exponentially growing recA cells, and is stimulated by DNA-damaging agents. We
      have previously found that the xonA and sbcD mutations, which inactivate
      exonuclease I (ExoI) and SbcCD nuclease, respectively, markedly suppress
      "reckless" DNA degradation in UV-irradiated recA cells. In the present work, we
      show that inactivation of exonuclease VII (ExoVII) by an xseA mutation
      contributes to attenuation of DNA degradation in UV-irradiated recA mutants. The
      xseA mutation itself has only a weak effect, however, it acts synergistically
      with the xonA or sbcD mutations in suppressing "reckless" DNA degradation. The
      quadruple xseA xonA sbcD recA mutants show no sign of DNA degradation during post
      irradiation incubation, suggesting that ExoVII, together with ExoI and SbcCD,
      plays a crucial role in regulating RecBCD-catalyzed chromosome degradation. We
      propose that these nucleases act on DSBs to create blunt DNA ends, the preferred
      substrates for the RecBCD enzyme. In addition, our results show that in UV
      irradiated recF recA(+) cells, the xseA, xonA, and sbcD mutations do not affect
      RecBCD-mediated DNA repair, suggesting that ExoVII, ExoI and SbcCD nucleases are
      not essential for the initial targeting of RecBCD to DSBs. It is possible that
      the DNA-blunting activity provided by ExoVII, ExoI and SbcCD is required for an
      exchange of RecBCD molecules on dsDNA ends during ongoing "reckless" DNA
      degradation.

PMID- 23123981
TI  - Use of oxygen at the end of life:  on what basis are decisions made?
AB  - Discussing and conducting research on end-of-life issues is often difficult.
      However, it is important to initiate a dialogue about various topics surrounding
      death and dying. This paper looks at the available scientific literature relating
      to oxygen use at the end of life, describes associated attitudes and beliefs, and
      presents some brief examples of institutional practices. The aim is to stimulate
      thoughtful reflection and encourage research on this important topic. There is
      limited research regarding oxygen use at the end of life, and many questions
      remain. Despite the difficulty with research in this area, there is a need to
      expand the data and awareness in this field. Several authors have questioned the
      use of oxygen in end-of-life care, and the evidence that oxygen use may not
      always be indicated is growing.

PMID- 23123983
TI  - The search for a higher power among terminally ill people with no previous
      religion or belief.
AB  - In a palliative care setting, there is evidence from the practice of spiritual
      care delivery to suggest that some terminally ill patients may seek, with varying
      degrees of openness and articulation, to connect with a higher power, or God,
      despite having expressed no previous interest in religion or belief. Developing a
      better understanding of the thoughts and feelings of such patients requires
      insight into the initial triggers of their search. In this small qualitative
      study involving six patients, fear, hope, and a natural connection are posited as
      possible prompts. The results highlight the complexity of ambivalent feelings
      toward a transcendent being that can be the focus of anger and blame while
      simultaneously offering a source of comfort and hope for an afterlife. Moreover,
      the study revealed something of the extent to which health professionals may feel
      limited in facilitating necessary discussion by a need to protect patients and
      themselves from entering an unfamiliar and complex area.

PMID- 23123982
TI  - Burnout in nurses working in Portuguese palliative care teams:  a mixed methods
      study.
AB  - Repeat contact with suffering, dying, and death is considered to be a risk factor
      for burnout among health professionals, particularly nurses working in palliative
      care. A mixed methods study was conducted to identify burnout levels, risk and
      protective factors, prevention strategies, and the emotional impact of working in
      palliative care among nurses in Portugal. A quantitative questionnaire was
      completed by nursing members of nine different palliative care teams and was
      supported by interviews and observation. Although the participants were exposed
      to risk factors, such as work overload, disorganisation, difficult relationships
      within the team and with patients' relatives, they showed a low risk of burnout. 
      These results appear to be related both to the protective factors identified
      namely the ethic of care in the relationship the nurses establish with patients,
      families, and within their teams-and to the preventive strategies they actively
      adopt for burnout prevention. The positive aspects of the nurses' roles help them
      to build a positive view of their work, which also promotes their own personal
      and professional development.

PMID- 23123984
TI  - Educating prison staff in the principles of end-of-life care.
AB  - End-of-life (EoL) care is a priority in health care and aims to provide services
      for all those who are dying, irrespective of their location. Providing this care
      to those in prison services is challenging. This paper reports a project that
      aimed to provide an education programme to both prison nurses and officers to
      support their understanding of EoL care and how it may be provided within the
      confines of the prison environment. On offer was a mixed-methodology education
      programme incorporating a pre-existing university module not specifically
      tailored to the prison setting. The mentorship of a clinical nurse specialist
      already known to the prison staff proved crucial to its successful
      implementation. Following the educational programme, both the nurses and the
      prison officers reported having a deeper understanding of the issues and more
      confidence in providing EoL care to prisoners who are patients. Further delivery
      of the programme to a wider group is planned, and similar initiatives nationally
      may provide a flexible, affordable approach to EoL care for those ending their
      days in prison.

PMID- 23123985
TI  - Developing clinical guidelines  for end-of-life care:  blending evidence and
      consensus.
AB  - BACKGROUND: Developing clinical practice guidelines (CPGs) is challenging,
      particularly in areas that are difficult to research such as end-of-life care.
      AIM: To describe the process that staff in a large regional health-care service
      in Victoria, Australia, used to develop CPGs for managing diabetes at the end of
      life. METHOD: An interdisciplinary advisory group was appointed, a structured
      literature review undertaken, personal illness accounts sourced, and a guiding
      philosophy formulated. Individual interviews were conducted with people with
      diabetes and their carers. Formative and summative evaluation was undertaken.
      RESULTS: No level I or II evidence was identified. The interviews yielded
      important information about how people wanted their diabetes managed. Formative
      evaluation enabled stakeholders to participate in developing the CPGs. The
      summative evaluation confirmed the CPGs are easy to use and appropriate to
      clinical staff. CONCLUSIONS: The CPG development process yielded the best current
      evidence on which to base care plans and person-centred CPGs.

PMID- 23123986
TI  - Experiences implementing a 6-month pilot of a 7-day community CNS service in an
      urban hospice in Scotland.
AB  - BACKGROUND: Patients and carers may face challenges in the out-of-hours period,
      with inadequate support and variations in service provision, including access to
      specialist palliative care. A pilot was undertaken to extend availability of the
      community clinical nurse specialist (CNS) team to include weekends and public
      holidays. AIM: To examine the need for a 7-day community CNS service. METHOD:
      Activity data was collected for 6 months and feedback was sought from service
      users and the CNS team. RESULTS: There were 132 out-of-hours telephone contacts
      in the 6-month period, generating 35 home visits. Almost two thirds of these
      calls were proactive, 'planned' contacts. Most unplanned calls (68%) were from a
      carer for advice about symptom management and support as the patient's condition
      changed. CONCLUSION: The pilot demonstrated the need for a CNS service 7 days a
      week, and the service is now embedded in practice. Seven-day working benefits
      patients and families while being valued by the professional team.

PMID- 23123988
TI  - Drug, devices, technologies, and techniques for blood management in minimally
      invasive and conventional cardiothoracic surgery: a consensus statement from the
      International Society for Minimally Invasive Cardiothoracic Surgery (ISMICS)
      2011.
AB  - OBJECTIVE: The objectives of this consensus conference were to evaluate the
      evidence for the efficacy and safety of perioperative drugs, technologies, and
      techniques in reducing allogeneic blood transfusion for adults undergoing cardiac
      surgery and to develop evidence-based recommendations for comprehensive
      perioperative blood management in cardiac surgery, with emphasis on minimally
      invasive cardiac surgery. METHODS: The consensus panel short-listed the potential
      topics for review from a comprehensive list of potential drugs, devices,
      technologies, and techniques. The process of short-listing was based on the need
      to prioritize and focus on the areas of highest importance to surgeons,
      anesthesiologists, perfusionists, hematologists, and allied health care involved
      in the management of patients who undergo cardiac surgery whether through the
      conventional or minimally invasive approach. MEDLINE, Cochrane Library, and
      Embase databases were searched from their date of inception to May 2011, and
      supplemental hand searches were also performed. Detailed methodology and search
      strategies are outlined in each of the subsequently published systematic reviews.
      In general, all relevant synonyms for drugs (antifibrinolytic, aprotinin, [Latin
      Small Letter Open E]-aminocaproic acid, tranexamic acid [TA], desmopressin,
      anticoagulants, heparin, antiplatelets, anti-Xa agents, adenosine diphosphate
      inhibitors, acetylsalicylic acid [ASA], factor VIIa [FVIIa]), technologies (cell
      salvage, miniaturized cardiopulmonary bypass (CPB) circuits, biocompatible
      circuits, ultrafiltration), and techniques (transfusion thresholds, minimally
      invasive cardiac or aortic surgery) were searched and combined with terms for
      blood, red blood cells, fresh-frozen plasma, platelets, transfusion, and
      allogeneic exposure. The American Heart Association/American College of
      Cardiology system was used to label the level of evidence and class of each
      recommendation. RESULTS AND RECOMMENDATIONS: Database search identified more than
      6900 articles, with 4423 full-text randomized controlled trials assessed for
      eligibility, and the final 125 systematic reviews and meta-analyses were used in
      the consensus conference. The results of the consensus conference, including the
      evidence-based statements and the recommendations, are outlined in the text, with
      references given for the relevant evidence that formed the basis for the
      statements and recommendations. RECOMMENDATIONS FOR ANTIFIBRINOLYTICS: The lysine
      analogs ?-aminocaproic acid (Amicar) and tranexamic acid (TA) reduce exposure to
      allogeneic blood inpatients undergoing on-pump cardiac surgery. These agents are
      recommended to be used routinely as part of a blood conservation strategy
      especially in patients at risk of undergoing onpump cardiac surgery (Class I,
      Level A). It is important not to exceed maximum TA total dosages (50Y100mg/kg)
      because of potential neurotoxicity in the elderly and open-heart procedures
      (Class IIb, Level C). Aprotinin is not recommended in adult cardiac surgery until
      further studies on its safety profile have been performed (Class III, Level A).
      RECOMMENDATIONS FOR TA IN OFF-PUMP CORONARY ARTERY BYPASS: Tranexamic acid may be
      recommended as part of a blood conservation strategy in high risk patients
      undergoing off-pump coronary artery bypass (OPCAB) surgery (Class I, Level
      A).Tranexamic acid dosing in OPCAB surgery needs further study particularly with
      regard to possible neurotoxicity such as seizures.In addition, the benefit-risk
      ratio in OPCAB needs further eludication because of the lower inherent risk for
      bleeding in this group (Class IIb, Level C). RECOMMENDATIONS FOR DDAVP: DDAVP can
      be considered for prophylaxis in coronary artery bypass grafting (CABG) surgery,
      in particular, for patients onASA within 7 days or prolonged CPB more than 140
      minutes (Class IIa, Level A). Caution should be used with the DDAVP infusion rate
      to avoid significant systemic hypotension (Class I, Level A). RECOMMENDATIONS FOR
      TOPICAL HEMOSTATICS: The routine use of topical antifibrinolytics in cardiac
      surgery isnot recommended (Class IIa, Level A). Topical fibrin sealants may be
      considered in clinical situations where conventional approaches of surgical and
      medical improvement of hemostasis are not effective, that is, with bleeding
      problems more local than generalized, bearing in mind the blackbox warning of
      bovine thrombin by the US Food and Drug Administration (Class IIb, Level
      C).Recommendations for FVIIa:Prophylactic use of FVIIa cannot be recommended
      because of a significant increase in the risk of thromboembolic events and stroke
      (Class IIa, Level A).Factor VIIa may be considered in clinical situations where
      conventional approaches of surgical and pharmacologic hemostasis have failed and
      uncontrollable hemorrhage poses a high risk of severe and life-threatening
      outcomes (Class IIb, Level B). RECOMMENDATIONS FOR ERYTHROPOIETIN PLUS IRON: It
      is reasonable to administer erythropoietin preoperatively to increase red blood
      cell mass in patients who are anemic or refuse blood products (such as for
      Jehovah's Witness faith) or who are likely to have postoperative anemia (Class
      IIa, Level A). RECOMMENDATIONS FOR ANTIPLATELETS BEFORE CARDIAC SURGERY:
      Acetylsalicylic acid may be continued until surgery (Class IIa,Level B) For
      stable elective CABG procedures with no drug-elutingstent, stop clopidogrel 5
      days before surgery (Class I, Level A).h For stable elective CABG procedures with
      drug-eluting stents less than 1 year old, consider continuing clopidogrel or
      heparin as abridge to surgery (Class IIb, Level C).h Direct-acting P2Y12 receptor
      antagonists may be a better alternative than clopidogrel in acute coronary
      syndrome patients undergoing CABG surgery (Class IIa, Level B). RECOMMENDATIONS
      FOR ANTIPLATELETS AFTER CARDIAC SURGERY: In stable CABG surgery (nonYacute
      coronary syndrome patients), the routine use of postoperative clopidogrel with
      ASAis not warranted (Class IIb, Level B). RECOMMENDATIONS FOR ACUTE NORMOVOLEMIC
      HEMODILUTION: Acute normovolemic hemodilution can be considered in selected
      patients with adequate preoperative hemoglobin to reduce post-CPB bleeding (Class
      IIa, Level A).The routine use of acute normovolemic hemodilution is not
      recommended (Class IIb, Level B). RECOMMENDATIONS FOR RETROGRADE AUTOLOGOUS
      PRIMING: Retrograde autologous priming is recommended as a blood conservation
      modality to reduce allogeneic blood transfusion for onpump cardiac surgery (Class
      I, Level A). RECOMMENDATIONS FOR CELL SALVAGE: Routine use of cell salvage is
      recommended in operations where an increased blood loss is expected (Class 1,
      Level A). Cell salvage should be used throughout the entire operation and not
      merely as a replacement for CPB cardiotomy suction (Class IIa, Level A).
      RECOMMENDATIONS: BIOCOMPATIBLE CPB CIRCUITS: The routine use of biocompatible
      coated CPB circuitry may be considered as part of a multimodal blood conservation
      program. However, the heterogeneity of surface-modified products, anticoagulation
      management, and CPB technique does not significantly impact surgical blood loss
      and transfusion needs (Class IIb,Level A). RECOMMENDATIONS FOR MINIATURIZED
      EXTRACORPOREAL CARDIOPULMONARY CIRCUIT VERSUS CONVENTIONAL EXTRACORPOREAL
      CARDIOPULMONARY CIRCUIT: Miniaturized extracorporeal cardiopulmonary circuit can
      be considered as a blood conservation technique to reduce allogeneic blood
      exposure (Class IIa, Level A); however, issues related to heparinization
      management and biocompatible coatings remain to be clarified. RECOMMENDATIONS FOR
      ULTRAFILTRATION (CONTINUOUS OR MODIFIED):h Ultrafiltration may be considered for
      blood conservation (Class IIb, Level A); however, the impact on clinically
      relevant outcomes remains unknown. RECOMMENDATIONS FOR PLATELET PLASMAPHERESIS:It
      is reasonable to recommend platelet plasmapheresis for blood management in
      cardiac surgery (Class IIa, Level A), although the impact on clinically relevant
      outcomes remains unknown. RECOMMENDATIONS FOR POINT-OF-CARE MONITORING:The
      evidence is too premature to recommend point-of-caretechnology for routine use
      because its use has not been shown to impact clinical outcome (Class IIb, Level
      A). RECOMMENDATIONS FOR SURGICAL TECHNIQUES FOR OPCAB, MINIMALLY INVASIVE
      STERNOTOMY FOR AORTIC VALVE SURGERY, MINIMALLY INVASIVE STERNOTOMY FOR MITRAL
      VALVE SURGERY, AND TRANSCATHETHER AORTIC VALVE IMPLANTATION: Although these
      minimally invasive procedures are not primarily selected for the purpose of blood
      management, the reduced allogeneic blood exposure should be considered in the
      balance of benefits and risks when selecting the appropriate surgery for
      patients.

PMID- 23123989
TI  - The results of the enclose II proximal anastomotic device in 178 off-pump
      coronary artery bypass surgeries.
AB  - OBJECTIVE: Enclose II is a new device for proximal coronary artery bypass
      anastomoses. We evaluated the safety and effectiveness of Enclose II in patients
      who underwent off-pump coronary artery bypass grafting (CABG). METHODS: Enclose
      II was used for isolated off-pump CABG in 178 patients at six heart centers
      between October 2005 and December 2009. The preoperative characteristics of the
      patients, complications related to Enclose II, and early graft patency rates were
      examined. RESULTS: A total of 222 proximal anastomoses were performed in 178
      patients using Enclose II. Forty-four of these patients had two proximal
      anastomoses using this device. New cerebral infarction that arose in two patients
      (1.1%) was not related to Enclose II. No aortic injury occurred. The graft
      patency rate was 96.4% at 1 year after surgery. CONCLUSIONS: Enclose II is a safe
      and useful assist device for proximal anastomoses in patients undergoing off-pump
      CABG.

PMID- 23123990
TI  - The application of robotic surgery in vascular medicine.
AB  - OBJECTIVE: The feasibility of robotically assisted laparoscopic aortic surgery
      has already been adequately demonstrated. Our clinical experience with robot
      assisted aortoiliac reconstruction for occlusive diseases, aneurysms, and hybrid
      procedures performed using the Da Vinci system is described below. METHODS:
      Between November 2005 and November 2011, we performed 225 robot-assisted
      laparoscopic aortoiliac procedures. One hundred seventy-four patients were
      prospectively evaluated for occlusive diseases, 43 patients for abdominal aortic
      aneurysm, two for common iliac artery aneurysm, two for splenic artery aneurysm,
      three for hybrid procedures, and one for endoleak II treatment after endovascular
      aneurysm repair. The robotic system was applied to construct the vascular
      anastomosis for thromboendarterectomy, for aortoiliac reconstruction with a
      closure patch, for dissection of the splenic artery, and for posterior peritoneal
      suturing. A combination of conventional laparoscopic surgeries and robotic
      surgeries was routinely included. A modified fully robotic approach without
      laparoscopic surgery was used in the last 55 cases in our series. RESULTS: Two
      hundred seventeen cases (96%) were successfully completed robotically; one
      patient's surgery was discontinued during laparoscopy because of heavy aortic
      calcification. In seven patients (3%), conversion was necessary. The 30-day
      mortality rate was 0.4%, and nonlethal postoperative complications were observed
      in 10 patients (4.4%). CONCLUSIONS: Our experience with robot-assisted
      laparoscopic surgery has demonstrated the feasibility of this technique for
      aortoiliac vascular and hybrid procedures. Compared with purely laparoscopic
      techniques, the Da Vinci robotic system facilitated the creation of the aortic
      anastomosis and shortened the aortic clamping time.

PMID- 23123991
TI  - Successful treatment of lone persistent atrial fibrillation by means of a hybrid
      thoracoscopic-transcatheter approach.
AB  - OBJECTIVE: Ablation strategies for the treatment of lone persistent atrial
      fibrillation (AF) have rapidly evolved during the past decade both with
      electrophysiological (EP) and surgical approaches. We investigated the safety and
      efficacy of a novel staged hybrid approach combining surgical thoracoscopic and
      EP ablation in patients with lone persistent AF. METHODS: Twenty-four consecutive
      patients with either persistent (three patients, 12.5%) or long-standing
      persistent (21 patients, 87.5%) isolated AF were prospectively enrolled: the mean
      age was 63.2 +/- 9.3 years, the mean left atrial dimension was 50.5 +/- 8 mm, and
      the mean AF duration was 82.7 months (range, 7-240 months). The surgical
      procedure consisted of a monolateral, right-sided, thoracoscopic closed-chest
      approach to perform a "box" lesion set with a temperature-controlled, internally
      cooled, radiofrequency monopolar device with suction adherence (Cobra Adhere XL;
      Estech, San Ramon, CA USA). A continuous monitoring rhythm device (Reveal XT;
      Medtronic, Minneapolis, MN USA) was implanted at the time of surgery in all
      patients for continuous long-term monitoring of the heart rhythm. RESULTS:
      Successful completion of the procedure was achieved in all cases, with a mean
      ablation time of 29 +/- 9 minutes and an overall procedural time of 84 +/- 16
      minutes. After surgical ablation, the exit block was documented in all cases,
      whereas the entrance block was achieved in 87.5% (21 of 24 patients). No
      intensive care unit stay was required, and no complications occurred
      postoperatively; hospital mortality was 0%. At a mean interval of 33 +/- 2 days
      after surgery, an EP study was performed: bidirectional block was confirmed in
      79.1% (19 of 24 patients), whereas gaps at the level of the box lesion were
      observed in 20.8% of the patients (5 of 24 patients). Additional transcatheter
      endocardial right- and left-sided lesions were performed in 62.5% of cases (15 of
      24 patients). At a mean follow-up of 28 months (range, 1-55 months), 87.5% of the
      patients (21 of 24 patients) are in sinus rhythm, and the incidence of left
      atrial flutter was 0%. CONCLUSIONS: The combination of thoracoscopic box lesion
      and transcatheter ablation in a staged hybrid approach proved to be safe,
      providing excellent mid-term clinical outcomes in patients with long-standing,
      isolated, persistent AF. Moreover, the implantable loop recorders documented such
      incremental benefits in sinus rhythm restoration for up to 28 months.

PMID- 23123992
TI  - Increasing surgical experience with off-pump coronary surgery does not mitigate
      the morbidity of emergency conversion to cardiopulmonary bypass.
AB  - OBJECTIVE: Emergency conversion during off-pump coronary artery bypass (OPCAB)
      confers significant morbidity. We sought to determine whether the outcomes in
      these patients have changed as our experience with off-pump techniques has
      increased. METHODS: Between January 1999 and December 2010, 4763 patients
      underwent coronary artery surgery. An off-pump strategy was attempted in 4415
      cases (92.7%). The results of the most recent 50 patients who required emergency
      conversion were compared with the preceding 50 conversions and with patients who
      underwent either OPCAB (n = 2737) or on-pump coronary surgery (coronary artery
      bypass grafting) (n = 268) during the same time frame. RESULTS: The emergency
      conversion rate was 2.27% (n = 100), being 2.97% for the first 50 cases and 1.77%
      for the subsequent 50 patients. The two sequential groups of emergency
      conversions had similar indications and timing of conversion and comparable
      outcomes. When compared with patients who underwent OPCAB, the more recent 50
      conversions had higher mortality (P = 0.002) and more frequent sternal wound
      infection (P = 0.036), hemorrhage requiring reoperation (P = 0.003), respiratory
      failure (P < 0.0001), and all-cause sepsis (P = 0.001). Compared with the on-pump
      group, the more recent conversions had higher mortality (P = 0.055) and a greater
      rate of postoperative sepsis (P = 0.002). CONCLUSIONS: The incidence of emergency
      conversion during OPCAB has decreased with increasing surgical experience;
      however, the morbidity in these patients remains essentially unchanged. The
      outcomes in these patients remain worse than those in nonconverted patients.
      Safer bailout strategies during OPCAB are still warranted.

PMID- 23123993
TI  - Video-assisted thymectomy with contralateral surveillance camera: a means to
      minimize the risk of contralateral phrenic nerve injury.
AB  - OBJECTIVE: Thymectomy for thymoma has traditionally been performed through
      midsternotomy that provides excellent exposure for a complete and safe resection.
      Minimally invasive alternatives have not been extensively evaluated for this
      disease process because data regarding the long-term oncologic effectiveness of
      these techniques remain to be established. Furthermore, video-assisted surgery as
      a unilateral approach may compromise the extension of the resection and could
      cause irreversible damage to the phrenic nerve of the opposite side. We evaluated
      the clinical feasibility and safety of a bilateral concomitant video-assisted
      approach with contralateral surveillance camera in patients undergoing thymectomy
      for thymoma. METHODS: Four patients (3 females, 1 male) with thymoma causing
      myasthenia gravis (MG) were operated thoracoscopically at our institute under
      general anesthesia with double-lumen endotracheal intubation. The patients were
      placed in a supine position, and a 5-mm 30-degree lens thoracoscope was
      introduced into the left pleural space. Two other 10-mm working channels were
      applied. En bloc thymectomy was then performed, including mediastinal and
      pericardial fat pads, other tissue, and pleura from the level of the thoracic
      inlet to the diaphragm. A second 5-mm thoracoscope was inserted into the right
      hemithorax, and it was kept inside during the entire procedure to allow lateral
      surveillance of the extension and safety of the resection. Carbon dioxide
      insufflation and valved ports were used. RESULTS: The duration of the operation
      was 90 +/- 72 minutes. Complete resection was achieved in all patients without
      any nerve injury. There were no perioperative adverse events. Gradual remission
      from extremity and ocular weakness was achieved after recovery. CONCLUSIONS: The
      ultimate surgical goal of thymectomy is to completely remove the gland and
      anterior mediastinal tissue without nerve injury. Bilateral concomitant video
      assisted thoracic thymectomy with a contralateral surveillance camera was found
      feasible and safe. Given the capability of our technique to perform a complete
      and extensive thymectomy associated with less invasiveness and beneficial
      effects, there seems to be a role for minimally invasive thymectomy in the
      treatment of thymoma.

PMID- 23123994
TI  - Ten years' follow-up of single-surgeon minimally invasive reparative surgery for
      degenerative mitral valve disease.
AB  - OBJECTIVE: Granted that minimally invasive mitral valve (MV) surgery short-term
      results were found to be equivalent to those achieved with traditional sternotomy
      with respect to perioperative morbidity and echocardiographic outcomes, little is
      known about the long-term efficacy of this approach. This report analyzes a 10
      year single-surgeon experience with minimally invasive MV surgery through a right
      minithoracotomy with peripheral cannulation and external aortic cross-clamping
      and MV repair (MVR) by direct vision. METHODS: We studied 179 patients (48%
      female) who underwent MVR between December 1999 and December 2010. Mean age was
      40.2 +/- 10.1 years (range, 15-67 years). One hundred seventy patients (95.0%)
      had degenerative diseases, and nine patients (5.0%) had endocarditic diseases.
      Repair techniques for degenerative disease with posterior leaflet prolapse (74
      patients, 43.5%) consisted of quadrangular resection (QR) and annuloplasty (AP)
      combined with sliding plasty (49 patients, 58.1%); for anterior leaflet prolapse
      (28 patients, 16.5%) and bileaflet prolapse (66 patients, 38.8%), edge-to-edge
      repair (EE) and AP; in 2 patients (1.2%), annular dilatation alone consisting of
      AP. Repair techniques for endocarditic disease consisted of EE in six patients
      (66.7%), perforation closure in two patients (22.2%), and QR combined with AP in
      one patient (11.1%). RESULTS: All patients survived the operation and were
      discharged with MV regurgitation (MR) less than 2+/4+. At 10 years' follow-up,
      overall survival was 98.7% +/- 1.2%, freedom from redo was 98.5% +/- 1.1%,
      freedom from MR recurrence (>2+/4+) in QR and in EE repair were, respectively,
      91.7% +/- 2.2% and 90.0% +/- 2.4% (P = not significant). The linearized rates of
      overall mortality, MR recurrence (>2+/4+), and redo at follow-up are 0.10% +/-
      0.10% per year, 0.63% +/- 0.26% per year, and 0.21% +/- 0.15% per year,
      respectively. CONCLUSIONS: Minimally invasive MVR can be performed with very good
      perioperative and long-term results. Freedom from MR greater than 2+/4+
      recurrence for patients with QR is equivalent to that with EE repair in our
      patient cohort.

PMID- 23123995
TI  - Augmented reality image guidance improves navigation for beating heart mitral
      valve repair.
AB  - OBJECTIVE: Emerging off-pump beating heart valve repair techniques offer patients
      less invasive alternatives for mitral valve (MV) repair. However, most of these
      techniques rely on the limited spatial and temporal resolution of transesophageal
      echocardiography (TEE) alone, which can make tool visualization and guidance
      challenging. METHODS: Using a magnetic tracking system and integrated sensors, we
      created an augmented reality (AR) environment displaying virtual representations
      of important intracardiac landmarks registered to biplane TEE imaging. In a
      porcine model, we evaluated the AR guidance system versus TEE alone using the
      transapically delivered NeoChord DS1000 system to perform MV repair with chordal
      reconstruction. RESULTS: Successful tool navigation from left ventricular apex to
      MV leaflet was achieved in 12 of 12 and 9 of 12 (P = 0.2) attempts with AR
      imaging and TEE alone, respectively. The distance errors of the tracked tool tip
      from the intended midline trajectory (5.2 +/- 2.4 mm vs 16.8 +/- 10.9 mm, P =
      0.003), navigation times (16.7 +/- 8.0 seconds vs 92.0 +/- 84.5 seconds, P =
      0.004), and total path lengths (225.2 +/- 120.3 mm vs 1128.9 +/- 931.1 mm, P =
      0.003) were significantly shorter in the AR-guided trials compared with
      navigation with TEE alone. Furthermore, the potential for injury to other
      intracardiac structures was nearly 40-fold lower when using the AR imaging for
      tool navigation. The AR guidance also seemed to shorten the learning curve for
      novice surgeons. CONCLUSIONS: Augmented reality-enhanced TEE facilitates more
      direct and safe intracardiac navigation of the NeoChord DS tool from left
      ventricular apex to MV leaflet. Tracked tool path results demonstrate fourfold
      improved accuracy, fivefold shorter navigation times, and overall improved safety
      with AR imaging guidance.

PMID- 23123996
TI  - Effects of percutaneous stimulation of both sympathetic and parasympathetic
      cardiac autonomic nerves on cardiac function in dogs.
AB  - OBJECTIVE: Augmentation of left ventricular (LV) contractility and heart rate
      (HR) by sympathetic nerve stimulation and amelioration of heart failure by vagal
      nerve stimulation has been reported. However, the effects of concomitant
      electrical stimulation of both sympathetic and parasympathetic cardiac nerves in
      tissues such as those of the cardiac plexus remain unclear. This study sought to
      assess acute changes in cardiac function and hemodynamics in response to
      endovascular cardiac plexus stimulation (CPS). METHODS: Twelve dogs received
      endovascular CPS via a bipolar catheter within the right pulmonary artery.
      Stimulation frequency (20 Hz) and pulse width (4 milliseconds) were fixed;
      voltage varied (range, 15-60 V). RESULTS: Results fell into three categories: 1,
      no response (n = 4); 2, an increase in systemic arterial pressure that was
      dependent on electrode placement (n = 4); and 3, a very reproducible and stable
      increase in aortic pressure (n = 4). In the third group, mean systolic aortic
      pressures, maximum value of the first derivative of LV pressure, and LV stroke
      work increased with stimulation (P < 0.02 for all parameters) as did cardiac
      output, end-systolic elastance, and preload recruitable stroke work (P = 0.03).
      Systemic and pulmonary vascular resistance, central venous pressure, pulmonary
      arterial pressure, and HR remained unchanged (P > 0.05). CONCLUSIONS: In contrast
      to conventional inotropic agents, endovascular CPS induced significant and
      selective increases in LV contractility without increasing HR. Efforts to
      optimize electrode placement and fixation will improve the reproducibility of
      endovascular CPS treatment.

PMID- 23123997
TI  - Transapical 29-mm Edwards SAPIEN-XT aortic valve in a 34-mm mitral annuloplasty
      ring.
AB  - A 71-year-old woman with severe congestive heart failure and failed mitral valve
      repair was referred for surgery. Because of her low ejection fraction, a valve-in
      ring procedure was suggested. There was a great difference in the given size for
      the 34-mm Carpentier-Edwards-Physio-Ring and the biggest available transcatheter
      valve of 29 mm from Edwards. Therefore, we did a "bench test." We expanded a 29
      mm Edwards SAPIEN-XT aortic valve in a 34-mm Carpentier-Edwards-Physio-Ring. It
      fitted well and turned out circular with good coaptation of the leaflets.
      Thereafter, a successful transapical mitral valve-in-ring implantation on
      cardiopulmonary bypass was performed, and additional leads for cardiac
      resynchronization was placed.

PMID- 23123998
TI  - "Kissing stents" as an adjunct to thoracic endovascular aortic repair: warts and
      all.
AB  - A 75-year-old man presented with symptomatic thoracic aneurysm involving the
      origin of the left subclavian artery. To obtain an adequate landing zone, a
      simultaneous stent was placed in the left common carotid artery. Until
      fenestrated and branch graft technology is more available, snorkel approaches may
      be an acceptable approach for patients with contraindications to open repair.

PMID- 23123999
TI  - Minimal-access left ventricular assist device explantation.
AB  - Patients on left ventricular assist device (LVAD) support can be successfully
      bridged to recovery. A novel explantation technique is reviewed. Six HeartMate II
      patients were successfully explanted off-pump through a combination of a left
      anterior minithoracotomy and a subxiphoid incision. A retrospective review of the
      institutional LVAD database was performed. The median LVAD support duration was
      191 days (range, 69-307 days). There was no procedural or 30-day mortality
      associated with the LVAD explantation, and all patients are in New York Heart
      Association I to II at a median follow-up of 688 days (range, 127-1033 days).
      This procedure was associated with minimal blood transfusion and short intensive
      care unit stay (median, 1 day; range, 1-5 days) and hospitalization (median, 4.5
      days; range, 3-19 days). One postexplant embolic cerebral infarct occurred. The
      HeartMate II LVAD can be safely explanted through a less conventional minimal
      access approach.

PMID- 23124000
TI  - Minimally invasive implantation of the myopore sutureless myocardial pacing lead.
AB  - Cardiac resynchronization therapy improves symptoms and survival of patients
      with congestive heart failure. Usually, the transvenous placement of the left
      ventricular lead is feasible, but in case of anatomic abnormalities of the
      coronary sinus, an unintended left phrenic nerve stimulation, a dislodgement of
      the percutaneous electrode, or a loss of capture of the electrode, surgical
      treatment should be considered. From January 2010 to September 2011, 15 patients
      underwent surgical implantation of the left ventricular lead after failure of
      transvenous placement. The MyoPore sutureless myocardial pacing lead (MSMPL) was
      implanted through a left minithoracotomy (~5 cm) under selective right lung
      ventilation. Time of surgery was 38.5 +/- 3.0 minutes, and no surgical
      complications or early deaths are reported so far. After 10.7 +/- 8.3 months of
      follow-up, no cases of late mortality, dislodgement, or loss of capture of the
      electrode are described. The use of the MSMPL is not novel, although the
      association with a minimally invasive approach may represent an alternative for a
      high-risk population. The screw-in of the lead ensures low impedance and
      threshold of stimulation (1.1 +/- 0.6 V at 0.5 milliseconds) both in early and
      medium terms. In conclusion, in case of failure of the transvenous approach, the
      MSMPL may be easily implanted through a left minithoracotomy, and the results are
      noteworthy.

PMID- 23124002
TI  - Detection and typing of cutaneous human papillomavirus types--a comparison of
      three different methods.
AB  - Cutaneous human papillomavirus (HPV) may play a role in the development of
      cutaneous squamous cell carcinoma. HPV copy numbers in cutaneous squamous cell
      carcinoma are very low and hence sensitive and reliable detection methods are
      important, particularly to examine the natural history of cutaneous HPV. In the
      present study, the presence of cutaneous HPV types was examined in 194 skin swabs
      and in a subgroup of 91 skin swabs, and compared using three different PCR based
      methods: (i) beta/gamma cutaneous HPV PCR reverse-line-blotting (BGC-PCR RLB),
      (ii) multiplex cutaneous papillomavirus genotyping (McPG) and (iii) FAP PCR. The
      HPV prevalence was 75% (68/91) with BGC-PCR RLB, 64% (124/194) with McPG and 72%
      (139/194) with FAP PCR. The agreement for the detection of HPV between the three
      methods in the subset of 91 samples was 73% (66/91; kappa=0.34) for BGC-PCR RLB
      and McPG, 75% (68/91; kappa=0.32) for BGC-PCR RLB and FAP PCR, and 69% (63/91;
      kappa=0.25) for McPG and FAP PCR. For McPG and FAP PCR, 194 specimens were tested
      in total, with an overall agreement of 66% (129/194; kappa=0.24) for the
      detection of HPV. The concordance between the three methods was moderate, which
      could be explained by different HPV types detectable with each method; the high
      number of multiple infections and the low viral copy number in human skin.
      Overall, many cutaneous HPV types were identified and multiple HPV types were
      found frequently in the human skin swabs.

PMID- 23124001
TI  - A PCR-RFLP method for typing human papillomavirus type 16 variants.
AB  - Infection with some types of human papillomavirus (HPV) is required for cervical
      cancer development, being HPV type 16 (HPV 16) the most common type in
      premalignant and malignant cervical lesions. DNA sequencing has revealed the
      existence of intratypic variants of HPV 16 whose genotyping is clinically useful
      for distinguishing between persistent and recurrent infections. From the
      epidemiological perspective, the frequency of diverse HPV 16 variants in several
      populations could correlate with the presence of precursor high-risk lesions in
      different anatomical locations. Currently, the "gold standard" method for
      identifying HPV 16 variants involves the sequencing of genomic regions to
      identify characteristic polymorphic sites. Although some other methods have been
      described, they require specialized or high-cost equipment. In this study, a
      robust and low cost procedure is described for HPV 16 variant typing, based on
      the long control region of the virus.

PMID- 23124004
TI  - A method of increasing the film intrinsic robustness of radiochromic film
      dosimetry.
AB  - The radiochromic film, which is used, in combination with a flatbed scanner has
      become a widely used tool for a quantitative evaluation of radiation dose in
      radiation therapy. One aspect of uncertainty using the radiochromic film is the
      magnitude of orientation effects when the orientation of the film is not kept
      constant during the digitization process. The aim of this note was to investigate
      the impact of using a combination of two crossed sheets of EBT2 film on various
      aspects of radiochromic film dosimetry. First the impact on the film sensitivity
      was studied. We also investigated the influence on orientation effects during
      scanning. The results show that the double crossed film combination increases the
      sensitivity with a factor 1.7-2.1 and practically eliminates the effects of film
      orientation on the optical density read-out and the lateral correction profiles.

PMID- 23124003
TI  - Comparative quantitative analysis of hepatitis C mutations at amino acids 70 and
      91 in the core region by the Q-Invader assay.
AB  - Hepatitis C virus (HCV) is a major worldwide public health problem, and mutations
      at amino acids 70 and 91 in the genotype 1b core region predict the effectiveness
      of combination therapy with peginterferon and ribavirin. An assay based on the Q
      Invader technology was developed to determine the relative ratios of the mutant
      to wild-type virus with high sensitivity. The assay detected a minor type plasmid
      that constituted only 1% of a mixture of plasmids containing wild-type and mutant
      sequences. The calculated ratios agreed with those of the template DNA. A total
      of 123 serum samples of HCV in Japan were examined with the Q-Invader assay. The
      Q-Invader assay detected all of the mutations that were detected by direct
      sequencing and even some mutants that direct sequencing could not. PCR with
      mutant specific primers confirmed those mutations found by the Q-Invader assay
      and not by direct sequencing. The Q-Invader assay, thus, is a useful tool for
      detecting mutations at positions 70 and 91 in the HCV-1b core region.

PMID- 23124009
TI  - Validation of the Hebrew version of the MoCA test as a screening instrument for
      the early detection of mild cognitive impairment in elderly individuals.
AB  - INTRODUCTION: The English version of the Montreal Cognitive Assessment (MoCA)
      test has been shown to be reliable in screening for mild cognitive impairment
      (MCI). However, the sensitivity and specificity of the Hebrew version of this
      instrument are yet to be determined. METHODS: The study population consisted of 2
      groups of older individuals, 74 patients diagnosed with MCI and 80 patients who
      were cognitively asymptomatic. Cognitive evaluation included the Mini-Mental
      State Examination (MMSE), Mindstreams computerized cognitive assessment, and the
      MoCA test. RESULTS: The Hebrew version of MoCA distinguished between cognitively
      asymptomatic older individuals and those with MCI, with a sensitivity of 94.6%
      and a specificity of 76.3%, using a cutoff of 26/30 points. CONCLUSIONS: The
      Hebrew version of the MoCA test is effective for identifying MCI in older
      patients. As a screening instrument for MCI, its higher sensitivity makes it
      preferable o the MMSE, which is used extensively in the clinical setting.

PMID- 23124010
TI  - Symptom profile of postoperative delirium in patients with and without dementia.
AB  - This study compares the symptom profile of patients with postoperative delirium
      after femoral neck fracture surgery in those with and without dementia. In this
      study, 129 patients of age >=70 years (mean age +/-SD, 86+/-6 yr, 72% women) with
      postoperative delirium, were included. Delirium and dementia were diagnosed
      according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth
      Edition) criteria. Of the 129 patients with delirium, 54 (42%) had a dementia
      disorder. Patients with delirium superimposed on dementia more often had any
      hyperactive and pure emotional delirium. Communication difficulties and symptoms
      such as restlessness/agitation, aggressive behavior, and irritability were more
      commonly found in the dementia group. In contrast, patients with delirium but
      without dementia were more often diagnosed with pure hypoactive and any psychotic
      delirium. The symptom profile of postoperative delirium varies according to
      whether it occurs in patients with or without dementia. This may indicate that
      postoperative delirium among patients with hip fracture differs based on the
      presence or absence of dementia.

PMID- 23124011
TI  - Co-occurrence of anemia, marginal vitamin B6, and folate status and depressive
      symptoms in older adults.
AB  - Although nutrient deficiencies are thought to play roles in the development of
      depression, observational studies have yielded inconsistent results. This study
      aimed to investigate whether multiple marginal nutrient deficiencies are
      associated with symptoms of depression in community-dwelling older Taiwanese.
      Data from 1371 elderly adults recruited from the Elderly Nutrition and Health
      Survey in Taiwan was used in this study. Depressive symptom scores on depressed
      mood and emotions affecting daily life were derived from the Medical Outcomes
      Study Short Form-36 (SF-36). Hemoglobin, serum ferritin, plasma vitamins B(6),
      B(12), and folate concentration, and erythrocyte transketolase and glutathione
      reductase activation coefficients were measured. After adjusting for age, gender,
      cognitive function, physical activity, disease history, and medication in the
      multivariate analysis, anemia, and marginal B(6) deficiency were significantly
      associated with the presence of depression symptoms, respectively. In addition,
      co-occurrence of vitamin B(6) with low folate level and co-occurrence of anemia
      either with low vitamin B(6) or with folate level were all associated with the
      depressive mood and with depressive emotions defined by SF-36 (odds ratios [OR]
      in the range of 2.32-7.13, all P values <=.05). The magnitude of the ORs is
      larger when the number of deficiencies increased. Elderly people with coexisting
      marginal deficiencies of nutrients involved in the S-adenosylmethionine and
      hemoglobin production were more likely to experience depressed mood and emotion
      that affect daily activity. Examining status of these nutrients is worthy of
      consideration for older adults with depressed symptoms.

PMID- 23124014
TI  - Evaluation of neophobia and its potential impact upon predator control
      techniques: a study on two sympatric foxes in southern Patagonia.
AB  - An alternative approach to increase the efficiency of predator control and
      selectivity is to consider the natural behavioural repertoire of the target
      species and how such behaviours may increase their vulnerability. Neophobia, or
      the hesitancy to approach a novel food item, object, or place, is an important
      factor influencing the investigative behaviour of animals, and its incorporation
      to predator control techniques may help to reduce losses of livestock to
      predators. In this study, we simultaneously evaluated the existence and intensity
      of neophobic responses in two sympatric fox species, the Culpeo (Pseudalopex
      culpaeus) and the Grey (P. griseus) foxes in southern Patagonia, Argentina. For
      this purpose, we used bait stations to compare fox behavioural responses in the
      absence (pre-treatment), presence (treatment) and removal (post-treatment) of a
      novel stimulus, which consisted of an orange PVC-traffic cone. Both fox species
      showed a neophobic response: bait-station visitation rates decreased (P=0.005 and
      P=0.048, for Culpeo and Grey foxes, respectively) in the presence of the novel
      object. The intensity of the response differed between species being higher for
      Culpeo foxes (approximately 80% of reduction in visitation rate during treatment
      for Culpeo foxes vs. 10% for Grey foxes). However, the bait-station visitation
      pattern after novel object removal indicated that animals probably increased
      exploration of the station. The high level of neophobia achieved by the Culpeo
      fox, together with an increase in post-treatment site exploration, suggests that
      behavioural manipulations (reduction of neophobia and its consequent increase in
      risk taking) could improve selective and efficient fox control in rural areas
      where livestock production is a major economic activity.

PMID- 23124012
TI  - The contribution of heart failure to sleep disturbances and depressive symptoms
      in older adults.
AB  - BACKGROUND: The aim of this study was to explore the associations between
      physical symptoms, sleep disturbances, and depressive symptoms in community
      dwelling elderly individuals, comparing persons with and without heart failure
      (HF). METHODS: A total of 613 older adults (mean age 78 years) underwent clinical
      and echocardiographic examinations. Questionnaires were used to evaluate sleep
      disturbances and depressive symptoms. A model was developed in those with HF (n =
      107) and compared with those without HF (n = 506). RESULTS: Cardiopulmonary
      symptoms (ie, dyspnea and nighttime palpitations) and pain had significant direct
      associations with sleep disturbances, which indirectly affected depressive
      symptoms. The model was essentially the same in those with and without HF except
      that the effect of sleep disturbances on depressive symptoms was stronger in
      those with HF (beta = 0.64 vs beta = 0.45, P = .006). CONCLUSION: In community
      dwelling older adults, regardless of their diagnosis, physical symptoms had a
      direct effect on sleep disturbances and an indirect effect on depressive
      symptoms.

PMID- 23124015
TI  - Variation in reproductive traits of members of the genus Canis with special
      attention to the domestic dog (Canis familiaris).
AB  - We compare differences in the reproductive strategies of "free-living" dogs with
      their wild relatives in the genus Canis, of which the dog is a very recently
      evolved member. The members of this genus display a greater range of parental
      motor patterns than generally seen in other species of Carnivora, including pair
      bonding and extended parental care; parents regurgitate to offspring and
      provision them with food for months to as long as a year. But the domestic dog
      does not routinely display these genus-typical behaviors. While this has
      generally been assumed to be a result of direct human intervention, humans have
      little reproductive control over the vast majority of domestic dogs. We analyze
      the low frequency of display of genus-typical behaviors and postulate that the
      dog's reproductive behaviors are an adaptation to permanent human settlement and
      the waste resources associated with it. Adaptation to this environment has
      decreased seasonality, increased the fecundity of unrestrained dogs and reduced
      the need for prolonged parental care. The consequences of greater fecundity and
      reduced parental care are compared to the reproductive behavior of other species
      of the genus.

PMID- 23124016
TI  - Sensitivity to tactile novelty in the terrestrial isopod, Porcellio scaber.
AB  - Invertebrates have been studied at biochemical, ecological, and behavioural
      levels, but current knowledge about the impact that learning may have on
      behaviour is rather sparse. The present study aimed to examine the sensitivity of
      isolated rough woodlice (Porcellio scaber, Latreille, 1804) to the tactile
      novelty of their environment. A simple way to test this issue was to refer to the
      place preference paradigm, traditionally used in vertebrates. In Experiment 1,
      woodlice were placed in a compartment for 30 min in order to assess their ability
      to develop habituation in the absence of reward. In Experiment 2, woodlice were
      exposed to a compartment for 20 min (habituation phase) and were then given free
      choice between that compartment and a novel compartment for 2 min (preference
      phase). Depending on test conditions, rewards (humidity and/or shelter) were
      present or absent in the familiar compartment. The familiar and novel
      compartments differed with respect to the texture of the floor. In Experiment 3,
      the floor texture was the same in the two compartments in order to control for a
      novelty effect. The main results indicate that woodlice exhibited increased
      locomotion time, increased distance travelled, and increased speed in the novel
      compartment compared to the familiar compartment. There was no preference for
      either compartment when the floor textures of both were identical.

PMID- 23124017
TI  - Comparison of food hoarding of two sympatric rodent species under interspecific
      competition.
AB  - Competition can greatly affect the food hoarding strategies of rodents and the
      fate of seeds hoarded. In order to understand the influence of interspecific
      competition on food caching behavior of sympatric rodents, we investigated food
      hoarding patterns of two sympatric rodent species, buff-breasted rat (Rattus
      flavipectus) and Chinese white-bellied rat (Niviventor confucianus), and compared
      their responses and adjustment in hoarding behavior under interspecific
      competition. The results showed that: (1) the buff-breasted rat larder hoarded
      seeds only, while Chinese white-bellied rat hoarded seeds in both larder and
      scatter forms; (2) two species of rodents both larder hoarded more seeds when
      competitors were present; and (3) the Chinese white-bellied rats adjusted their
      seed hoarding from scatter to larder when competitors were introduced, which
      reduced the seed availability. Therefore, we concluded that rodents would adjust
      their food hoarding strategy when interspecific competitors were present, and
      this may produce a different effect on the fate of seeds and the recruitment of
      plants. This article is part of a Special Issue entitled: insert SI title.

PMID- 23124018
TI  - A facile and green ultrasonic-assisted synthesis of BSA conjugated silver
      nanoparticles.
AB  - The formation and growth of hybrid nanoparticles of a protein BSA and silver by
      ultrasonic assistance were tracked by surface plasmon resonance signal of silver
      nanoparticles and light scattering. The hybrid nanoparticles were characterized
      by surface plasmon resonance spectra, light scattering, TEM, circular dichroism
      spectroscopy and zeta potential. Size along with the spherical shape of the
      nanoparticles could be controlled and nanoparticles with diameters ranging from 8
      to 140 nm could be obtained, depending upon the ultrasonication time (15-30 min)
      and molar ratio of AgNO(3)/BSA (20-200). The role of single free thiol group in
      the reduction of silver ions was also investigated by using DTNB modified BSA and
      protein conjugated silver nanoparticles were formed even with thiol modified BSA.
      The growth and size of the nanoparticles were governed by ultrasonic assisted
      Ostwald ripening. BSA conjugated with silver nanoparticles showed changes in the
      secondary structure with an increase in the beta sheet structure to 33% as
      compared to 7% in native BSA as determined by CD spectra. Zeta potential
      measurements in the pH range of 2.0-12.0 demonstrated that the surface charges of
      the BSA conjugated silver nanoparticles were similar to that of native BSA
      suggesting that surface charges and overall three dimensional structure of BSA
      did not change much. This approach provides a strategy for completely green
      synthesis of hybrid nanoparticles consisting of a biological entity and an
      inorganic material. This is the first application of ultrasonic assistance in
      formation of such hybrid nanomaterials in aqueous media.

PMID- 23124019
TI  - Using double-stranded DNA probes to promote specificity in target capture.
AB  - The most prevalent nucleic acid detection schemes employ single-stranded
      sequences as probes for capture and detection of oligonucleotide targets in
      solution. In these systems elevated temperature conditions are generally used to
      enhance specificity and limit false positives from occurring with mismatched
      targets. In contrast, the current study uses a strand displacement approach
      between soluble targets and double-stranded DNA probes (dsProbes) immobilized on
      microspheres. In our approach the displacement of reporter strands from the
      dsProbes by the target of interest is promoted by the affinity differences
      between the reporter strand and the soluble DNA or RNA targets for the
      immobilized sequences. While displacement activity occurred readily in center
      mismatched dsProbes with a weaker intrinsic affinity, incorporating a two base
      long single-stranded segment at the free end of the immobilized dsProbes resulted
      in target discrimination not observed for dsProbes possessing only a center
      mismatch.

PMID- 23124020
TI  - Hair waving natural product: Dillenia indica seed sap.
AB  - Knowing keratin is the main component and mechanical strength of hair a study was
      performed to evaluate whether Dillenia indica seed sap can affect molecular
      strength of hair or not. In the present study the human hair collected from
      barber shop waste were subjected to purified sap for 12 h and then analysed using
      Fourier transform infrared spectroscopy (FTIR) for documenting evidence for
      keratin degradation. Further the deterioration was confirmed by thermo
      gravimetric analysis (TGA) and scanning electron microscopy (SEM).

PMID- 23124021
TI  - Preformulation studies of mucoadhesive tablets for carbamazepine sublingual
      administration.
AB  - The purpose of this research work was the realization of a bi-layered
      mucoadhesive dosage form intended for carbamazepine sublingual administration and
      planned in order to obtain a unidirectional drug release and diffusion only
      across buccal mucosa avoiding the liberation in the buccal environment. Bi
      layered tablets were constituted by an impermeable ethyl cellulose backing layer
      and a mucoadhesive layer. The latter was composed by a blend of a semisynthetic
      polymer, as hydroxyethyl cellulose or hydroxypropyl methylcellulose, and a
      synthetic polymer as, Carbopol((r)), physically mixed in different ratios. The
      active ingredient carbamazepine was homogeneously dispersed in the mucoadhesive
      layer. The prepared formulations were carefully characterized by thickness,
      friability, swelling index, matrix erosion, ex vivo and in vivo mucoadhesive
      force and time, moreover patient acceptability was evaluated as well. Tablets
      constituted by Carbopol((r)):hydroxypropyl methylcellulose (25%:75%) and
      Carbopol((r)):hydroxyethyl cellulose (75%:25%) showed the best properties and for
      this reason were submitted to in vitro release studies. Both tablet groups gave
      good results in terms of ex vivo and in vivo bioadhesive force and time giving a
      sustained release.

PMID- 23124022
TI  - Bioactive lipid mediators in skin inflammation and immunity.
AB  - The skin is the primary barrier from the outside environment, protecting the host
      from injury, infectious pathogens, water loss and solar ultraviolet radiation. In
      this role, it is supported by a highly organized system comprising elements of
      innate and adaptive immunity, responsive to inflammatory stimuli. The cutaneous
      immune system is regulated by mediators such as cytokines and bioactive lipids
      that can initiate rapid immune responses with controlled inflammation, followed
      by efficient resolution. However, when immune responses are inadequate or mounted
      against non-infectious agents, these mediators contribute to skin pathologies
      involving unresolved or chronic inflammation. Skin is characterized by active
      lipid metabolism and fatty acids play crucial roles both in terms of structural
      integrity and functionality, in particular when transformed to bioactive
      mediators. Eicosanoids, endocannabinoids and sphingolipids are such key bioactive
      lipids, intimately involved in skin biology, inflammation and immunity. We
      discuss their origins, role and influence over various cells of the epidermis,
      dermis and cutaneous immune system and examine their function in examples of
      inflammatory skin conditions. We focus on psoriasis, atopic and contact
      dermatitis, acne vulgaris, wound healing and photodermatology that demonstrate
      dysregulation of bioactive lipid metabolism and examine ways of using this
      insight to inform novel therapeutics.

PMID- 23124023
TI  - The action site of the synthetic kainoid (2S,3R,4R)-3-carboxymethyl-4-(4
      methylphenylthio)pyrrolidine-2-carboxylic acid (PSPA-4), an analogue of Japanese
      mushroom poison acromelic acid, for allodynia (tactile pain).
AB  - We previously demonstrated that intrathecal (i.t.) administration of acromelic
      acid A (Acro-A) induced allodynia in mice and that simultaneous administration of
      (2S,3R,4R)-3-carboxymethyl-4-(phenylthio)pyrrolidine-2-carboxylic acid (PSPA-1),
      an Acro-A analogue, attenuated the Acro-A-induced allodynia. To clarify a
      mechanism of PSPA-1, we attached methyl radical to PSPA-1 and synthesized
      (2S,3R,4R)-3-carboxymethyl-4-(4-methylphenylthio) pyrrolidine-2-carboxylic acid
      (PSPA-4) and [(11)C]PSPA-4 for behavioral and autoradiography studies. Although
      PSPA-4 inhibited the Acro-A-induced allodynia in a dose-dependent manner from 1
      to 10 fg/mouse, PSPA-4 itself induced allodynia at 10 to 100 pg/mouse. In vitro
      autoradiography, [(11)C]PSPA-4 was specifically bound to the rat brain and spinal
      cord, and the binding was significantly displaced by PSPA-1 and kainic acid, but
      not by AMPA and antagonists of NMDA, AMPA and kainate receptors. Conversely,
      [(3)H]kainate was specifically bound to the rat brain and the dorsal horn of
      spinal cord, and the binding was significantly displaced by PSPA-1 and PSPA-4.
      The PSPA-4-induced allodynia was blocked by the AMPA/kainate antagonist
      GYKI53655, but not by kainate antagonists NS102 and UBP296. PSPA-4 increased
      intracellular Ca(2+) concentration in 27.9% of cultured dorsal root ganglion
      neurons responding to glutamate, much higher than kainate in 10.9% of them. Taken
      together, these results suggest that PSPA-4 attenuated the Acro-A-induced
      allodynia at low doses and induced allodynia at high doses via a binding site
      different from known kainate antagonists. The development of a radio-labeled PSPA
      4 will enable us to promote the understanding of the action mechanism not only of
      Acro-A, but also of pain transmission in the periphery and central nervous
      system.

PMID- 23124024
TI  - Highly fluorescent core-shell hybrid nanoparticles templated by a unimolecular
      star conjugated polymer for a biological tool.
AB  - Highly fluorescent core-shell hybrid nanoparticles were readily fabricated from
      the soft template of a unimolecular star conjugated polymer (HCP-star-PDMAEMA).
      Since the hyperbranched conjugated polymer (HCP) core was isolated by a silicon
      dioxide (SiO(2)) shell, HCP@SiO(2) with excellent optical properties was retained
      in the aqueous solution for potential application in biological imaging.

PMID- 23124025
TI  - IL-4 and IL-13 employ discrete signaling pathways for target gene expression in
      alternatively activated monocytes/macrophages.
AB  - Monocytes/macrophages are innate immune cells that play a crucial role in the
      resolution of inflammation. In the presence of the Th2 cytokines interleukin-4
      (IL-4) and interleukin-13 (IL-13), they display an anti-inflammatory profile and
      this activation pathway is known as alternative activation. In this study we
      compare and differentiate pathways mediated by IL-4 and IL-13 activation of human
      monocytes/macrophages. Here we report differential regulation of IL-4 and IL-13
      signaling in monocytes/macrophages starting from IL-4/IL-13 cytokine receptors to
      Jak/Stat-mediated signaling pathways that ultimately control expression of
      several inflammatory genes. Our data demonstrate that although the receptor
      associated tyrosine kinases Jak2 and Tyk2 are activated after the recruitment of
      IL-13 to its receptor (containing IL-4Ralpha and IL-13Ralpha1), IL-4 stimulates
      Jak1 activation. We further show that Jak2 is upstream of Stat3 activation and
      Tyk2 controls Stat1 and Stat6 activation in response to IL-13 stimulation. In
      contrast, Jak1 regulates Stat3 and Stat6 activation in IL-4-induced monocytes.
      Our results further reveal that although IL-13 utilizes both IL
      4Ralpha/Jak2/Stat3 and IL-13Ralpha1/Tyk2/Stat1/Stat6 signaling pathways, IL-4 can
      use only the IL-4Ralpha/Jak1/Stat3/Stat6 cascade to regulate the expression of
      some critical inflammatory genes, including 15-lipoxygenase, monoamine oxidase A
      (MAO-A), and the scavenger receptor CD36. Moreover, we demonstrate here that IL
      13 and IL-4 can uniquely affect the expression of particular genes such as dual
      specificity phosphatase 1 and tissue inhibitor of metalloprotease-3 and do so
      through different Jaks. As evidence of differential regulation of gene function
      by IL-4 and IL-13, we further report that MAO-A-mediated reactive oxygen species
      generation is influenced by different Jaks. Collectively, these results have
      major implications for understanding the mechanism and function of alternatively
      activated monocytes/macrophages by IL-4 and IL-13 and add novel insights into the
      pathogenesis and potential treatment of various inflammatory diseases.

PMID- 23124026
TI  - Resveratrol ameliorates ionizing irradiation-induced long-term hematopoietic stem
      cell injury in mice.
AB  - Our recent studies showed that total body irradiation (TBI) induces long-term
      bone marrow (BM) suppression in part by induction of hematopoietic stem cell
      (HSC) senescence through NADPH oxidase 4 (NOX4)-derived reactive oxygen species
      (ROS). Therefore, in this study we examined whether resveratrol (3,5,4'
      trihydroxy-trans-stilbene), a potent antioxidant and a putative activator of
      Sirtuin 1 (Sirt1), can ameliorate TBI-induced long-term BM injury by inhibiting
      radiation-induced chronic oxidative stress and senescence in HSCs. Our results
      showed that pretreatment with resveratrol not only protected mice from TBI
      induced acute BM syndrome and lethality but also ameliorated TBI-induced long
      term BM injury. The latter effect is probably attributable to resveratrol
      mediated reduction of chronic oxidative stress in HSCs, because resveratrol
      treatment significantly inhibited TBI-induced increase in ROS production in HSCs
      and prevented mouse BM HSCs from TBI-induced senescence, leading to a significant
      improvement in HSC clonogenic function and long-term engraftment after
      transplantation. The inhibition of TBI-induced ROS production in HSCs is probably
      attributable to resveratrol-mediated downregulation of NOX4 expression and
      upregulation of Sirt1, superoxide dismutase 2 (SOD2), and glutathione peroxidase
      1 expression. Furthermore, we showed that resveratrol increased Sirt1 deacetylase
      activity in BM hematopoietic cells; and Ex527, a potent Sirt1 inhibitor, can
      attenuate resveratrol-induced SOD2 expression and the radioprotective effect of
      resveratrol on HSCs. These findings demonstrate that resveratrol can protect HSCs
      from radiation at least in part via activation of Sirt1. Therefore, resveratrol
      has the potential to be used as an effective therapeutic agent to ameliorate TBI
      induced long-term BM injury.

PMID- 23124028
TI  - Targeting neurohumoral signaling to treat pulmonary hypertension: the right
      ventricle coming into focus.

PMID- 23124027
TI  - GRK2-mediated inhibition of adrenergic and dopaminergic signaling in right
      ventricular hypertrophy: therapeutic implications in pulmonary hypertension.
AB  - BACKGROUND: The cause and consequences of impaired adrenergic signaling in right
      ventricular failure/hypertrophy (RVH) are poorly understood. We hypothesized that
      G protein-coupled receptor kinase-2 (GRK2)-mediated uncoupling of beta-adrenergic
      receptor signaling impairs inotropic reserve. The implications of right
      ventricular (RV) adrenergic remodeling for inotrope selection and the therapeutic
      benefit of interrupting Gbetagamma-GRK2 interaction, using gallein, were tested.
      METHODS AND RESULTS: Chamber-specificity and cellular localization of adrenergic
      remodeling were compared in rodent RVH associated with pulmonary arterial
      hypertension (PAH-RVH; SU5416+chronic-hypoxia or Monocrotaline) versus pulmonary
      artery banding-induced RVH (PAB-RVH). Results were corroborated in RV arrays from
      10 PAH patients versus controls. Inotropic reserve was assessed in RV- and left
      ventricular-Langendorff models and in vivo. Gallein therapy (1.8 mg/kg/day *2
      weeks) was assessed. Despite similar RVH, cardiac output (58.3+/-4.9 versus
      82.9+/-4.8 mL/min; P<0.001) and treadmill distance (41.5+/-11.6 versus 244.1+/
      12.4 m; P<0.001) were lower in PAH-RVH versus PAB-RVH. In PAH-RVH versus PAB-RVH
      there was greater downregulation of beta1-, alpha1- and dopamine-1 receptors,
      more left ventricular involvement, and greater impairment of RV contractile
      reserve. RV GRK2 activity increased in parallel with a reduction in both
      adrenergic receptor expression and inotrope-stimulated cAMP levels (P<0.01).
      beta1-receptor downregulation also occurred in human PAH-RVH. Dobutamine was
      superior to dopamine as an RV inotrope, both ex vivo and in vivo. CONCLUSIONS:
      GRK2-mediated desensitization-downregulation of adrenergic and dopaminergic
      receptors impairs inotropic reserve in PAH-RVH. Acute inotropic support in RVH is
      best accomplished by dobutamine, reflecting its better coupling to adenylyl
      cyclase and the reliance of dopamine on dopamine-1-receptor signaling, which is
      impaired in RVH. Inhibiting Gbetagamma-GRK2 interactions has therapeutic benefit
      in RVH.

PMID- 23124029
TI  - Fetal heart rate predictors of long QT syndrome.
AB  - BACKGROUND: Fetal long QT syndrome (LQTS) is associated with complex arrhythmias
      including torsades de pointes and 2 degrees  atrioventricular block. Sinus
      bradycardia has also been associated with fetal LQTS, but little is known of this
      rhythm manifestation. Our purpose was to characterize the fetal heart rate
      (FHR)/gestational age (GA) profile of fetal LQTS. METHODS AND RESULTS: We
      ascertained fetal LQTS subjects by family history (Group 1) or fetal arrhythmia
      referral (Group 2). We compared FHR in LQTS subjects versus normal fetuses. To
      identify FHR predictors of LQTS, we calculated a bradycardia index as % of LQTS
      FHR recordings either <=110 beats per minute (obstetric standard) or <=3(rd)
      percentile for GA. Among 42 LQTS subjects, 26 were in Group 1 and 16 in Group 2.
      There were 536 normal fetuses. The bradycardia index was only 15% for FHR <=110
      beats per minute, but 66% for FHR <=3rd percentile for GA. Ten fetuses with
      complex arrhythmias also had severe and sustained sinus bradycardia throughout
      gestation. Identifying a fetal proband in Group 2 resulted in LQTS diagnosis in 9
      unsuspected members of 6 families. CONCLUSIONS: FHR varies by GA in both normal
      and LQTS fetuses. Postnatal evaluation of neonates with FHR <=3(rd) percentile
      for GA may improve ascertainment of LQTS in fetuses, neonates, and undiagnosed
      family members.

PMID- 23124030
TI  - Sodium, blood pressure, and cardiovascular disease: further evidence supporting
      the American Heart Association sodium reduction recommendations.
AB  - Recent reports of selected observational studies and a meta-analysis have stirred
      controversy and have become the impetus for calls to abandon recommendations for
      reduced sodium intake by the US general population. A detailed review of these
      studies documents substantial methodological concerns that limit the usefulness
      of these studies in setting, much less reversing, dietary recommendations.
      Indeed, the evidence base supporting recommendations for reduced sodium intake in
      the general population remains robust and persuasive. The American Heart
      Association is committed to improving the health of all Americans through
      implementation of national goals for health promotion and disease prevention,
      including its recommendation to reduce dietary sodium intake to <1500 mg/d.

PMID- 23124031
TI  - Conversion of cardiovascular conference abstracts to publications.
AB  - BACKGROUND: The transition of scientific knowledge from discovery into practice
      is less than ideal. A key step in this translation occurs when presentations from
      major meetings are published in peer-reviewed literature, yet the completeness
      and speed of this process are not known. We performed a systematic and automated
      evaluation of rates, timing, and correlates of publication from scientific
      abstracts presented at 3 major cardiovascular conferences. METHODS AND RESULTS:
      Using an automated computer algorithm, we searched the ISI Web of Science to
      identify peer-reviewed publications of abstracts presented at the American Heart
      Association (AHA), American College of Cardiology (ACC), and European Society of
      Cardiology (ESC) scientific sessions from 2006 to 2008. We compared abstract
      publication rates and journal impact factor between the 3 meetings using
      multivariable logistic regression modeling. From 2006 to 2008, 11 365, 5005, and
      10 838 abstracts were presented at the AHA, ACC, and ESC meetings, respectively.
      Overall, 30.6% of presented abstracts were published within 2 years of the
      conference; ranging from 34.5% for AHA to 29.5% for ACC to 27.0% for ESC
      (P<0.0001). Five years after conference presentation in 2005, these rates had
      risen slightly to 49.7% for AHA, 42.6% for ACC, and 37.6% for ESC (P<0.0001).
      After adjustment for abstract characteristics and contributing countries,
      abstracts presented at the AHA meeting remained more likely for publication
      relative to the ESC (adjusted odds ratio, 1.24; 95% confidence interval, 1.16
      1.34) and the ACC (adjusted odds ratio, 1.20; 95% confidence interval, 1.11
      1.29). Median impact factors for subsequent publications varied from 4.8
      (interquartile range, 3.8-10.1) for AHA to 4.0 (interquartile range, 3.1-7.5) for
      ACC and 3.9 (quartile 1-3, 2.5-5.8) for ESC (P for difference between groups
      <0.01). Clinical science and population science were less likely to be published
      compared with basic science. CONCLUSIONS: One third of abstracts were translated
      into publications by 2 years after presentation and less than one half by 5 years
      after presentation. Our findings suggest that efforts to understand the barriers
      to publication and to facilitate the rapid dissemination of new knowledge are
      needed to speed up the transition of scientific discovery into clinical practice.

PMID- 23124032
TI  - Exercise physiology in the catheterization laboratory: still alive and well!

PMID- 23124033
TI  - Synergistic adaptations to exercise in the systemic and coronary circulations
      that underlie the warm-up angina phenomenon.
AB  - BACKGROUND: The mechanisms of reduced angina on second exertion in patients with
      coronary arterial disease, also known as the warm-up angina phenomenon, are
      poorly understood. Adaptations within the coronary and systemic circulations have
      been suggested but never demonstrated in vivo. In this study we measured central
      and coronary hemodynamics during serial exercise. METHODS AND RESULTS: Sixteen
      patients (15 male, 61+/-4.3 years) with a positive exercise ECG and exertional
      angina completed the protocol. During cardiac catheterization via radial access,
      they performed 2 consecutive exertions (Ex1, Ex2) using a supine cycle ergometer.
      Throughout exertions, distal coronary pressure and flow velocity were recorded in
      the culprit vessel using a dual sensor wire while central aortic pressure was
      recorded using a second wire. Patients achieved a similar workload in Ex2 but
      with less ischemia than in Ex1 (P<0.01). A 33% decline in aortic pressure
      augmentation in Ex2 (P<0.0001) coincided with a reduction in tension time index,
      a major determinant of left ventricular afterload (P<0.001). Coronary stenosis
      resistance was unchanged. A sustained reduction in coronary microvascular
      resistance resulted in augmented coronary flow velocity on second exertion (both
      P<0.001). These changes were accompanied by a 21% increase in the energy of the
      early diastolic coronary backward-traveling expansion, or suction, wave on second
      exercise (P<0.05), indicating improved microvascular conductance and enhanced
      left ventricular relaxation. CONCLUSIONS: On repeat exercise in patients with
      effort angina, synergistic changes in the systemic and coronary circulations
      combine to improve vascular-ventricular coupling and enhance myocardial
      perfusion, thereby potentially contributing to the warm-up angina phenomenon.

PMID- 23124034
TI  - Rhythm versus rate control therapy and subsequent stroke or transient ischemic
      attack in patients with atrial fibrillation.
AB  - BACKGROUND: Stroke is a debilitating condition with an increased risk in patients
      with atrial fibrillation. Although data from clinical trials suggest that both
      rate and rhythm control are acceptable approaches with comparable rates of
      mortality in the short term, it is unclear whether stroke rates differ between
      patients who filled prescriptions for rhythm or rate control therapy. METHODS AND
      RESULTS: We conducted a population-based observational study of Quebec patients
      >=65 years with a diagnosis of atrial fibrillation during the period 1999 to 2007
      with the use of linked administrative data from hospital discharge and
      prescription drug claims databases. We compared rates of stroke or transient
      ischemic attack (TIA) among patients using rhythm (class Ia, Ic, and III
      antiarrhythmics), versus rate control (beta-blockers, calcium channel blockers,
      and digoxin) treatment strategies (either current or new users). The cohort
      consisted of 16 325 patients who filled a prescription for rhythm control therapy
      (with or without rate control therapy) and 41 193 patients who filled a
      prescription for rate control therapy, with a mean follow-up of 2.8 years
      (maximum 8.2 years). A lower proportion of patients on rhythm control therapy
      than on rate control therapy had a CHADS(2) (congestive heart failure,
      hypertension, age >=75 years, diabetes mellitus, and previous stroke or TIA)
      score of >=2 (58.1% versus 67.0%, P<0.001). Treatment with any antithrombotic
      drug was comparable in the 2 groups (76.8% in rhythm control versus 77.8% in rate
      control group). Crude stroke/TIA incidence rate was lower in patients treated
      with rhythm control in comparison with rate control therapy (1.74 versus 2.49,
      per 100 person-years, P<0.001). This association was more marked in patients in
      the moderate- and high-risk groups for stroke according to the CHADS(2) risk
      score. In multivariable Cox regression analysis, rhythm control therapy was
      associated with a lower risk of stroke/TIA in comparison with rate control
      therapy (adjusted hazard ratio, 0.80; 95% confidence interval, 0.74, 0.87). The
      lower stroke/TIA rate was confirmed in a propensity score-matched cohort.
      CONCLUSIONS: In comparison with rate control therapy, the use of rhythm control
      therapy was associated with lower rates of stroke/TIA among patients with atrial
      fibrillation, in particular, among those with moderate and high risk of stroke.

PMID- 23124035
TI  - Prognosis of individuals with asymptomatic left ventricular systolic dysfunction
      in the multi-ethnic study of atherosclerosis (MESA).
AB  - BACKGROUND: Limited data exist on the prevalence, associations, and prognosis of
      individuals with asymptomatic left ventricular systolic dysfunction (ALVSD),
      especially in populations without previous clinical cardiovascular disease (CVD).
      METHODS AND RESULTS: Kaplan-Meier and Cox proportional hazard analyses were used
      to assess the association between ALVSD, defined as left ventricular ejection
      fraction <50%, and adjudicated incident congestive heart failure (CHF), all-cause
      mortality, and CVD events. Of 5004 participants, 112 participants had CHF, 321
      had a CVD event, and 278 died after 9 years of follow-up. The overall prevalence
      of ALVSD was 1.7%, with a higher prevalence in blacks (2.6%). ALVSD had a worse
      cardiovascular risk profile and was also associated with increased risk in
      unadjusted and adjusted models for incident CHF (HR [hazard ratio] [95% CI
      {confidence interval}]: 12.0 [7.04-20.3], P<0.0001 and 8.69 [4.89-15.45], P<0.001
      respectively), CVD (HR [95% CI]: 3.32 [1.98-5.58], P<0.001 and 2.21 [1.30-3.73],
      P=0.003 respectively), and all-cause mortality (HR [95% CI]: 3.47 [2.03-5.94],
      P<0.0001 and 2.00 [1.13-3.54], P=0.017, respectively). A 10% decrement in left
      ventricular ejection fraction at baseline was associated with an increase in risk
      in unadjusted and adjusted models for clinical CHF (HR [95% CI]: 2.17 [1.82
      2.63], P<0.0001 and 2.13 [1.73-2.51], P<0.001, respectively) and all-cause
      mortality (HR [95% CI]: 1.22 [1.05-1.41], P=0.009 and 1.17 [1.00-1.36], P=0.047,
      respectively). Among the subset of participants with ALVSD, the left ventricular
      mass index was particularly informative about risk for incident CHF (c
      index=0.74). CONCLUSIONS: ALVSD is uncommon in individuals without previous
      clinical CVD, but it is associated with high risk for CHF, CVD, and all-cause
      mortality. The left ventricular mass index had good discrimination for incident
      CHF in Multi-Ethnic Study of Atherosclerosis (MESA) participants with ALVSD.

PMID- 23124036
TI  - Regulation of p53 by reversible post-transcriptional and post-translational
      mechanisms in liver and skeletal muscle of an anoxia tolerant turtle, Trachemys
      scripta elegans.
AB  - The red-eared slider turtle (Trachemys scripta elegans) exhibits well-developed
      natural anoxia tolerance that depends on multiple biochemical adaptations,
      including anoxia-induced hypometabolism. We hypothesized that signaling by the
      p53 protein could aid in establishing the hypometabolic state by arresting the
      cell cycle, protecting against DNA damage as well as altering pathways of energy
      metabolism. Immunoblotting was used to evaluate the regulation and post
      transcriptional modifications of p53 in liver and skeletal muscle of red-eared
      slider turtles subjected to 5h or 20h of anoxic submergence. Tissue specific
      regulation of p53 was observed with the liver showing a more rapid activation of
      p53 in response to anoxia as well as differential expression of seven serine
      phosphorylation and two lysine acetylation sites when compared with skeletal
      muscle. Protein expression of MDM2, a major p53 inhibitor, was also examined but
      did not change during anoxia. Reverse-transcriptase PCR was used to assess
      transcript levels of selected p53 target genes (14-3-3sigma, Gadd45alpha and Pgm)
      and one microRNA (miR-34a); results showed down-regulation of Pgm and up
      regulation of the other three. These findings show an activation of p53 in
      response to anoxia exposure and suggest an important role for the p53 stress
      response pathway in regulating natural anoxia tolerance and hypometabolism in a
      vertebrate facultative anaerobe.

PMID- 23124037
TI  - Identification of MRI1, encoding translation initiation factor eIF-2B subunit
      alpha/beta/delta-like protein, as a candidate locus for infantile epilepsy with
      severe cystic degeneration of the brain.
AB  - Several neurodegenerative disorders are known to predominantly affect the white
      matter of the brain including vanishing white matter disease (VWMD), an autosomal
      recessive disorder characterized by leukodystrophy of varying severity in
      addition to variable systemic involvement. We report a consanguineous Arab family
      with three affected children, all of whom presented with severe neonatal epilepsy
      and profound neurodegenerative disease characterized by marked leukodystrophy
      with white matter cavitation mimicking VWMD. We combined autozygome and exome
      analysis to identify a novel variant in the gene encoding a member of the eIF2B
      related family of proteins (MRI1). This is a poorly understood family of proteins
      of unclear function. Our results represent the first link between a variant in a
      member of this family and a human disease, and suggest that it converges with the
      highly homologous eIF2B, known to be mutated in VWMD, on the molecular
      pathogenesis of neurodegeneration.

PMID- 23124038
TI  - Characterization of the first adult de novo case of
      46,X,der(Y)t(X;Y)(p22.3;q11.2).
AB  - Herein, we describe a case of an infertile man detected in postnatal diagnosis
      with FISH characterization and array-CGH used for genome-wide screening which
      allowed the identification of a complex rearrangement involving sex chromosomes,
      apparently without severe phenotypic consequences. The deletion detected in our
      patient has been compared with previously reported cases leading us to propose a
      hypothetical diagnostic algorithm that would be useful in similar clinical
      situations, with imperative multi disciplinary approach integrated with genetic
      counseling. Our patient, uniquely of reproductive age, is one of six reported
      cases of duplication of Xp22.3 (~8.4Mb) segment and contemporary deletion of Yq
      (~42.9Mb) with final karyotype as follows: 46,X,der(Y),t(X;Y)(Ypter
      >Yq11.221::Xp22.33->Xpter).ish der(Y) (Yptel+,Ycen+,RP11-529I21+,RP11-506M9-Yqtel
      ,Xptel+). arrXp22.33p22.31(702-8,395,963, 8,408,289x1), Yq11.221q12
      (14,569,317x1, 14,587,321-57,440,839x0).

PMID- 23124040
TI  - Novel PTEN germline mutation in a family with mild phenotype: difficulties in
      genetic counseling.
AB  - PTEN gene (phosphatase and tensin homolog deleted on chromosome ten, MIM 601628)
      is a tumor suppressor gene implicated in PTEN hamartoma tumor syndromes (PHTS)
      including Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome and Proteus-like
      syndrome. PTEN mutations have been more recently reported in children with
      macrocephaly and autism spectrum disorders or mental retardation, without other
      symptoms of PHTS. Although tumor risk has not been evaluated in these patients
      and their relatives, the same surveillance as for Cowden syndrome is usually
      proposed. We report a family including patients carrying a novel PTEN mutation
      and presenting with a mild phenotype consisting of macrocephaly, hypotonia during
      the first year of life and mild learning disabilities, without autistic features.
      None of these patients exhibited PTHS-related symptoms such as tumors, lipomas,
      vascular malformations or pigmented macules of the glans penis. This report
      raises the question of extending the indications of PTEN mutation screening to
      familial macrocephaly with learning disabilities. Detection of a mutation in this
      family led to difficult questions about surveillance, genetic counseling and
      familial information since the mother declined tumor screening and disclosure of
      genetic risk information to at-risk relatives.

PMID- 23124039
TI  - Angelman syndrome and severe infections in a patient with de novo 15q11.2-q13.1
      deletion and maternally inherited 2q21.3 microdeletion.
AB  - Angelman syndrome is a neurodevelopmental disorder characterized by mental
      retardation, severe speech disorder, facial dysmorphism, secondary microcephaly,
      ataxia, seizures, and abnormal behaviors such as easily provoked laughter. It is
      most frequently caused by a de novo maternal deletion of chromosome 15q11-q13
      (about 70-90%), but can also be caused by paternal uniparental disomy of
      chromosome 15q11-q13 (3-7%), an imprinting defect (2-4%) or in mutations in the
      ubiquitin protein ligase E3A gene UBE3A mostly leading to frame shift mutation.
      In addition, for patients with overlapping clinical features (Angelman-like
      syndrome), mutations in methyl-CpG binding protein 2 gene MECP2 and cyclin
      dependent kinase-like 5 gene CDKL5 as well as a microdeletion of 2q23.1 including
      the methyl-CpG binding domain protein 5 gene MBD5 have been described. Here, we
      describe a patient who carries a de novo 5Mb-deletion of chromosome 15q11.2-q13.1
      known to be associated with Angelman syndrome and a further, maternally inherited
      deletion 2q21.3 (~364kb) of unknown significance. In addition to classic features
      of Angelman syndrome, she presented with severe infections in the first year of
      life, a symptom that has not been described in patients with Angelman syndrome.
      The 15q11.2-q13.1 deletion contains genes critical for Prader-Willi syndrome, the
      Angelman syndrome causing genes UBE3A and ATP10A/C, and several non-imprinted
      genes: GABRB3 and GABRA5 (both encoding subunits of GABA A receptor), GOLGA6L2,
      HERC2 and OCA2 (associated with oculocutaneous albinism II). The deletion 2q21.3
      includes exons of the genes RAB3GAP1 (associated with Warburg Micro syndrome) and
      ZRANB3 (not disease-associated). Despite the normal phenotype of the mother, the
      relevance of the 2q21.3 microdeletion for the phenotype of the patient cannot be
      excluded, and further case reports will need to address this point.

PMID- 23124041
TI  - A Japanese child with geleophysic dysplasia caused by a novel mutation of FBN1.
AB  - Geleophysic dysplasia (GD) is a rare disorder characterized by severe short
      stature, short hands and feet, limited joint mobility, skin thickening,
      characteristic facial features (e.g., a "happy" face), and cardiac valvular
      disorders that often result in an early death. The genes ADAMTSL2 (a disintegrin
      like and metalloprotease with thrombospondin type 1 motif-like 2) and FBN1
      (fibrillin 1) were recently identified as causative genes for GD. Here, we
      describe a 10-year-old Japanese female with GD who was born to non-consanguineous
      parents. At the age of 11 months, she was referred to our hospital because of
      very short stature for her age (-4.4 standard deviations of the age-matched
      value) and a "happy" face with full cheeks, a shortened nose, hypertelorism, and
      a long and flat philtrum, characteristic of GD. Her hands and feet were small,
      her skin was thickened, and her joint mobility was generally limited. She had
      cardiac valvular disorders and history of recurrent respiratory failure. Mutation
      analysis revealed no abnormalities in ADAMTSL2. However, analysis of FBN1
      revealed a novel heterozygous mutation (c.5161T>T/G) in exon 41, which encodes
      transforming growth factor-beta-binding protein-like domain 5 (TB5). GD is an
      extremely rare disorder and, to our knowledge, only one case of GD with an FBN1
      mutation has been reported in Japan. Similar to the previously reported cases of
      GD, the mutation in the current patient was located in the TB5 domain, which
      suggests that abnormalities in this domain of FBN1 are responsible for GD.

PMID- 23124042
TI  - GRIM-19 inhibits the STAT3 signaling pathway and sensitizes gastric cancer cells
      to radiation.
AB  - Gastric cancer is one of the most common malignancies, and radiation resistance
      is one of the key obstacles in gastric cancer treatment. In this study, we
      demonstrate that "genes associated retinoid-IFN induced mortality-19" (GRIM-19)
      expression was lower in patients with radiotherapy-resistant tumors compared to
      patients with radiotherapy-sensitive tumors. In order to further investigate the
      effects of GRIM-19 expression on the radiation response in gastric cancer cells,
      we established BGC-803 clones stably expressing exogenous GRIM-19. We found that
      the percentage of apoptotic cells was higher in cells expressing GRIM-19 than
      untransfected cells post-radiation treatment. Furthermore, caspase-3, -8, and -9
      activity was significantly increased in GRIM-19-expressing cells compared to
      untransfected cells after radiation. Finally, we demonstrate that expression of
      GRIM-19 in BGC-803 cells suppresses accumulation of STAT3. Collectively, these
      data show that GRIM-19 expression sensitizes BGC-803 cells to radiation, and this
      is likely due to suppression of STAT3 accumulation. In summary, our results
      indicate that GRIM-19 expression might be a useful therapy to enhance apoptosis
      in gastric cancer cells in response to radiation treatment.

PMID- 23124043
TI  - Identification of a missense mutation in the melusin-encoding ITGB1BP2 gene in a
      patient with dilated cardiomyopathy.
AB  - In a heterogeneous cohort of patients (n=255) with sporadic and familial dilated
      cardiomyopathy (DCM), we searched for novel disease-associated mutations in the
      human melusin-encoding ITGB1BP2 gene and found only one missense mutation, which
      was a substitution of alanine for glycine at position 313 located in the carboxy
      terminal spacer region of the molecule. This point mutation (c.938C>G) was
      identified in a 45-year-old male with familial DCM and severe impairment of left
      ventricular function, but was absent in 300 healthy control subjects. However,
      its functional significance in the context of heart failure is unclear, as this
      amino acid substitution was predicted to be without disease-causing effects. In
      this report, we confirm the low prevalence of mutations and single nucleotide
      polymorphisms in the coding sequence of the human melusin gene in patients with
      DCM, ruling out the possibility that genetic variations in this myocardially
      transcribed gene may have a significant impact on the epidemiology of DCM-induced
      heart failure.

PMID- 23124044
TI  - cDNA cloning and the response to overfeeding in the expression of stearoyl-CoA
      desaturase 1 gene in Landes goose.
AB  - Stearoyl-CoA desaturase 1 (SCD1) is a rate limiting enzyme in the biosynthesis of
      monounsaturated fatty acids. It has been cloned from several species: Rattus
      norvegicus, Mus musculus, Homo Sapiens and Gallus gallus, but not from Anser
      anser. This study was conducted to isolate the SCD1 cDNA sequence and investigate
      the effect of overfeeding on SCD1 gene tissue expression in Landes goose. The
      complete cDNA is 3294 bp in length, with an ORF of 1.083 bp encoding a predicted
      polypeptide of 360 amino acids and 5'/3'-UTR of 74 and 2137 bp, respectively.
      Quantitative real time PCR (qPCR) was used to examine SCD1 expression in heart,
      liver, spleen, lung, kidney, gizzard, glandular stomach, intestine, crureus,
      pectoral muscle, hypothalamus and adipose tissue (abdominal fat) in both the
      overfed and control group. SCD1 mRNA was highly expressed in goose fatty liver,
      and the expression levels of SCD1 in liver and fat of overfeeding group were more
      than double that of the control group. During the overfeeding period, SCD1
      expression in liver and adipose tissue reached the highest level after 70 days,
      but declined at 79 days. In the control group, after fasting 24h, the expression
      level of SCD1 gene in tissues declined sharply. However, SCD1 gene expression in
      hypothalamus was unaffected. The results of this study provide a theoretical
      basis to study the relationship between SCD1 gene expression and the formation of
      fatty liver of Landes goose in response to overfeeding.

PMID- 23124045
TI  - Cloning and expression analysis of the cytochrome P450c17s enzymes during the
      reproductive cycle in ovoviviparous Korean rockfish (Sebastes schlegeli).
AB  - Cytochrome P450c17 (CYP17, 17alpha-hydroxylase/17, 20-lyase) plays a critical
      role in the production of androgens and estrogens in vertebrates. We isolated the
      full length cDNAs of P450c17-I and P450c17-II from Sebastes schlegeli. The cDNA
      sequences of P450c17-I and P450c17-II encoded 515 and 533 amino acid residues
      respectively. The putative P450c17-I and P450c17-II enzymes of Korean rockfish
      share high sequence identity with that of Japanese flounder (92% and 81%)
      respectively. Our current study describes that P450c17s of Korean rockfish are
      mainly expressed in gonads, head kidney and kidney by RT-PCR. Quantitative real
      time PCR showed that the expression patterns of Korean rockfish P450c17s were
      developmental stage-dependency. In addition, the testosterone (T) and
      gonadosomatic index (GSI) levels further support the important role of P450c17-I
      during shift in steroidogenesis. Taken together, this study provides information
      about the Korean rockfish P450c17s characterization and mRNA expression as such
      helps in further understanding of its function in gonadal development.

PMID- 23124049
TI  - Definitions in children's palliative care: black and white or shades of grey?

PMID- 23124046
TI  - Identification of a novel mutation in ZAP70 and prenatal diagnosis in a Turkish
      family with severe combined immunodeficiency disorder.
AB  - Protein tyrosine kinases (PTKs) play an important role in T cell development and
      activation. In vitro and in vivo defects, resulting in variable deficiencies in
      thymic development and in T cell antigen receptor (TCR) signal transduction, in
      PTKs have been shown. ZAP70, one of those PTKs, is a 70-kDa tyrosine
      phosphoprotein and associates with the zeta chain and undergoes tyrosine
      phosphorylation following TCR stimulation. It is expressed in T and natural
      killer (NK) cells. Several mutations were shown to lead to an autosomal recessive
      form of severe combined immunodeficiency disease (SCID). Here, we present a
      family with a novel mutation in ZAP70. The proband, the second child of the first
      cousin parents of Turkish origin, was diagnosed with SCID having R514C mutation
      on homozygous state. She had decreased CD8(+) T and natural killer cells, normal
      CD4(+) T cells, high serum Ig E level, perivascular dermatitis and ichthyosis.
      This article presents clinical features of a novel mutation on ZAP70 and the
      first prenatal molecular diagnosis of ZAP70 deficiency. Different mutations in
      ZAP70 and related phenotypes reported in the literature are also discussed.

PMID- 23124050
TI  - Advocating for palliative care for an ageing population:  living to the end.

PMID- 23124048
TI  - Modification of small interfering RNAs to prevent off-target effects by the sense
      strand.
AB  - OBJECTIVE: There is a broad therapeutic potential for the application of small
      interfering RNAs (siRNAs). However, one has to ensure that siRNAs act
      specifically, only targeting the expression of one gene. Off-target effects
      raised by the sense strand have to be eliminated. METHODS AND RESULTS: We
      examined a particular bidirectional siRNA molecule, able to knockdown
      intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor receptor-1
      (TNFR-1) by the sense or antisense strand, respectively. Transfection of human
      venous endothelial cells with an unmodified siRNA molecule led to equal silencing
      of ICAM-1 and TNFR-1. In contrast, modified siRNA was able to knockdown ICAM-1
      and TNFR-1 separately, with only the antisense strand. DISCUSSION: We found the
      modified siRNAs to inhibit off-target effects originated by the sense strand. Our
      approach demonstrates one possibility to modify siRNAs before starting a clinical
      approach to eliminate off-target effects.

PMID- 23124051
TI  - Nonsmoking policy  in Danish hospices.
AB  - The Danish Smoke-free Environments Act 2007 aimed to prevent the harmful health
      effects of secondhand smoking. It requires employers to take practicable steps to
      ensure smoke-free environments for all, i.e. employees as well as members of the
      public (visitors, clients, customers, etc). Palliative care aims for a holistic
      approach that takes into account all aspects of patients' psychological,
      physical, and social needs. This may be challenged by a smoke-free policy in an
      end-of-life care setting. This paper looks at the concept of smoke-free standards
      in Danish end-of-life care settings.

PMID- 23124047
TI  - Baseline reach and adoption characteristics in a randomized controlled trial of
      two weight loss interventions translated into primary care: a structured report
      of real-world applicability.
AB  - BACKGROUND: Although the Diabetes Prevention Program (DPP) lifestyle intervention
      reduced type 2 diabetes incidence by 58% among high-risk adults at academic
      centers, it requires translation into typical primary care settings. Using
      baseline data from the Evaluation of Lifestyle Interventions to Treat Elevated
      Cardiometabolic Risk in Primary Care (E-LITE) randomized controlled trial, we
      evaluated the potential of its two DPP-based interventions to reach their target
      populations and be adopted into routine use. METHODS: Overweight/obese adults
      with increased cardiometabolic risk enrolled from one primary care clinic. Using
      the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) model,
      we assessed reach with data on patient identification, participation, and
      representativeness, and adoption with data on intervention feasibility and
      potential for organizational diffusion. RESULTS: The target population was
      identified by searching electronic health records. Contact was attempted for 2391
      patients who completed initial screening by phone (56% uptake) or online (44%).
      Most (88%) of those screened ineligible were not within the target population;
      12% were excluded because of research requirements. Conservatively estimated
      participation rate was 44%. Participants (n=241) included 54% men and had a mean
      (SD) age of 52.9 years (10.6) and body mass index of 32 kg/m(2) (5.4). Regarding
      adoption, all clinic physicians agreed to participate. The feasibility of
      intervention implementation and dissemination was enhanced by leveraging existing
      intervention, training, and primary care resources. CONCLUSIONS: E-LITE's
      lifestyle interventions had fair-to-good potential for primary care reach and
      adoption. Our trial evidence and structured reporting may inform real-world
      implementation of translational trials by health networks, physicians, and
      payers.

PMID- 23124052
TI  - Interventional pain management  in the palliative care patient.
AB  - For the majority of patients, cancer pain can be treated using the World Health
      Organization cancer pain guidelines; however, for 10-20% of patients with
      advanced cancer, adequate pain control cannot be achieved using these methods
      owing to disease pathophysiology preventing administration/absorption of pain
      medications or intolerance due to opioid toxicities. The need to expand analgesic
      treatment when oral, transdermal, and intravenous therapies fail requires
      exploration of interventional pain management techniques such as neuraxial (e.g.
      epidural and intrathecal) infusion therapies and neurolytic interventions. Nurses
      caring for patients with cancer pain should develop their knowledge of these
      multimodal approaches to cancer pain management.

PMID- 23124053
TI  - Oral care in nursing practice:  a pragmatic representation.
AB  - Oral care for patients receiving non-specialist palliative care has been reported
      to be lacking in several respects. The present study explored the oral care
      social representation of nurses and health-care assistants providing non
      specialist palliative care. A mixed methodology utilising a questionnaire and
      focus groups was adopted. The research identified difficulties in providing oral
      care in this setting. The participants reported managing their emotions around
      carrying out oral care. They had resources available and were convinced of the
      positive effects. However, their personal efficacy needed to be reinforced and
      they needed to receive positive feedback.

PMID- 23124054
TI  - Use of electronic data collection  to assess pain in thalassaemia:  a feasibility
      study.
AB  - AIM: To assess the feasibility of collecting electronic pain data from
      thalassaemia patients, based on its acceptability and convenience to the
      participants and study team. METHODS: Participants in the Thalassemia Clinical
      Research Network Assessment of Pain Survey Study completed the Brief Pain
      Inventory (BPI) quarterly by paper or phone interview. Participants in a substudy
      completed the BPI Short Form daily over three non-consecutive transfusion cycles
      through an automated telephone system. RESULTS: The consent rate for the main
      study was 93%, with 93% retention. The substudy had 75% retention, with more than
      75% of scheduled calls completed. Regular monitoring of enrollment, missed calls,
      data quality, and the performance of the subcontractor for the automated system
      was crucial to fulfillment of the study goals. CONCLUSIONS: Use of electronic
      data collection for patient-reported outcomes was convenient for both patients
      and study personnel but required human interactions beyond the automated system
      to maximise data quantity and quality.

PMID- 23124055
TI  - The lived experience of patients receiving radiotherapy for head and neck cancer:
      a literature review.
AB  - It is estimated that 60% of patients diagnosed with head and neck cancer will
      receive radiotherapy at some stage in their disease trajectory. The aim of this
      literature review was to find and analyse papers pertaining to the lived
      experiences of patients with head and neck cancer receiving radiotherapy. The
      review identified a limited number of high-quality research papers focusing on
      this topic, with only 10 papers fitting the inclusion/exclusion criteria. The
      majority of the investigative studies were not generalisable owing to small
      sample sizes and many of them being conducted in only one centre. However, the
      findings do highlight and contribute to the understanding of the lived
      experiences of this patient group and provide some insight into the unique
      physical, social, and psychological difficulties they encounter as a result of
      their treatment. There appears to be a need for further high-level research into
      these patients, particularly focusing on the provision of support and information
      prior to, during, and following radiotherapy. Further attention needs to be paid
      to preparing patients for the slow recovery following radiotherapy.
      Interventional studies are also required to develop clinical guidelines and
      protocols that can assist health professionals in meeting the holistic needs of
      this patient group.

PMID- 23124057
TI  - Raman spectroscopic analysis of human skin tissue sections ex-vivo: evaluation of
      the effects of tissue processing and dewaxing.
AB  - Raman spectroscopy coupled with K-means clustering analysis (KMCA) is employed to
      elucidate the biochemical structure of human skin tissue sections and the effects
      of tissue processing. Both hand and thigh sections of human cadavers were
      analyzed in their unprocessed and formalin-fixed, paraffin-processed (FFPP), and
      subsequently dewaxed forms. In unprocessed sections, KMCA reveals clear
      differentiation of the stratum corneum (SC), intermediate underlying epithelium,
      and dermal layers for sections from both anatomical sites. The SC is seen to be
      relatively rich in lipidic content; the spectrum of the subjacent layers is
      strongly influenced by the presence of melanin, while that of the dermis is
      dominated by the characteristics of collagen. For a given anatomical site, little
      difference in layer structure and biochemistry is observed between samples from
      different cadavers. However, the hand and thigh sections are consistently
      differentiated for all cadavers, largely based on lipidic profiles. In dewaxed
      FFPP samples, while the SC, intermediate, and dermal layers are clearly
      differentiated by KMCA of Raman maps of tissue sections, the lipidic
      contributions to the spectra are significantly reduced, with the result that
      respective skin layers from different anatomical sites become indistinguishable.
      While efficient at removing the fixing wax, the tissue processing also
      efficiently removes the structurally similar lipidic components of the skin
      layers. In studies of dermatological processes in which lipids play an important
      role, such as wound healing, dewaxed samples are therefore not appropriate.
      Removal of the lipids does however accentuate the spectral features of the
      cellular and protein components, which may be more appropriate for retrospective
      analysis of disease progression and biochemical analysis using tissue banks.

PMID- 23124058
TI  - Use of Raman spectroscopy in the analysis of nickel allergy.
AB  - Raman spectra of the skin of subjects with nickel allergy are analyzed and
      compared to the spectra of healthy subjects to detect possible biochemical
      differences in the structure of the skin that could help diagnose metal allergies
      in a noninvasive manner. Results show differences between the two groups of Raman
      spectra. These spectral differences can be classified using principal component
      analysis. Based on these findings, a novel computational technique to make a fast
      evaluation and classification of the Raman spectra of the skin is presented and
      proposed as a noninvasive technique for the detection of nickel allergy.

PMID- 23124059
TI  - Selection of interdependent genes via dynamic relevance analysis for cancer
      diagnosis.
AB  - Microarray analysis is widely accepted for human cancer diagnosis and
      classification. However the high dimensionality of microarray data poses a great
      challenge to classification. Gene selection plays a key role in identifying
      salient genes from thousands of genes in microarray data that can directly
      contribute to the symptom of disease. Although various excellent selection
      methods are currently available, one common problem of these methods is that
      genes which have strong discriminatory power as a group but are weak as
      individuals will be discarded. In this paper, a new gene selection method is
      proposed for cancer diagnosis and classification by retaining useful intrinsic
      groups of interdependent genes. The primary characteristic of this method is that
      the relevance between each gene and target will be dynamically updated when a new
      gene is selected. The effectiveness of our method is validated by experiments on
      six publicly available microarray data sets. Experimental results show that the
      classification performance and enrichment score achieved by our proposed method
      is better than those of other selection methods.

PMID- 23124060
TI  - Clinical impact of the leptin to soluble leptin receptor ratio on subclinical
      carotid atherosclerosis in patients with type 2 diabetes.
AB  - AIM: The adipocyte-derived hormone leptin plays a key role in the regulation of
      food intake and energy expenditure. Recent studies have suggested that leptin is
      also involved in the pathogenesis of obesity-associated atherosclerosis and
      cardiovascular disease. In this study, we investigated the associations of leptin
      and the soluble leptin receptor (sOb-R) with atherosclerosis in patients with
      type 2 diabetes. METHODS: Three hundred seventeen type 2 diabetic subjects were
      enrolled in this cross-sectional study. Fasting plasma leptin and sOb-R
      concentrations were measured by enzyme-linked immunosorbent assays. The intima
      media thickness (IMT) of the common carotid artery was measured by ultrasound.
      RESULTS: The IMT was significantly associated with sOb-R concentrations, age,
      diabetes duration, serum creatinine (sCre) levels, and systolic blood pressure
      (SBP), but not with leptin concentrations or the leptin/sOb-R ratio. The
      concentrations of leptin (r=0.478, p<0.001) and the sOb-R (r= -0.404, p<0.001)
      and the leptin/sOb-R ratio (r=0.501, p<0.001) were strongly correlated with IMT
      in subjects treated with insulin for glycemic control, but not in those treated
      with diet alone or oral hypoglycemic agents. Multiple regression analysis,
      including age, sex, diabetes duration, body mass index, SBP, HbA1c,
      triglycerides, LDL-cholesterol, sCre, smoking, and insulin therapy, revealed that
      plasma leptin and the leptin/sOb-R ratio were independently associated with IMT
      in subjects treated with insulin. CONCLUSIONS: Plasma leptin and the leptin/sOb-R
      ratio are associated with atherosclerosis in patients with type 2 diabetes on
      insulin therapy, and these associations were independent of obesity and other
      cardiovascular risk factors.

PMID- 23124061
TI  - The protective immune response against Pseudorabies virus induced by DNA
      vaccination is impaired if the plasmid harbors a functional Porcine circovirus
      type 2 rep and origin of replication.
AB  - A plasmid rendered replicative in mammalian cells by inserting the Porcine
      circovirus 2 (PCV2) origin of replication and replicase gene (Ori-rep) has been
      previously constructed. The aim of the present study was to evaluate if the
      replication capacity of this plasmid could be advantageously used to improve the
      protective immunity induced by DNA vaccination. In this case we used the porcine
      Pseudorabies virus (PrV) DNA vaccination model. The replicative capacity of the
      DNA vaccine did not improve the protective immunity against PrV in pigs, but on
      the contrary the presence of the PCV2 Ori-rep sequence was harmful in the
      induction of this immunity compared to an equivalent but non-replicative DNA
      vaccine. In addition, the distribution and the persistence of the replicative and
      non-replicative plasmids inside the body were the same. This is the first study
      showing an in vivo deleterious effect of the replicative active PCV2 Ori-rep on
      the natural and specific protection against PrV infection.

PMID- 23124063
TI  - DNA methyltransferase3A as a molecular switch mediating the neural tube-to-neural
      crest fate transition.
AB  - Here, we explore whether silencing via promoter DNA methylation plays a role in
      neural versus neural crest cell lineage decisions. We show that DNA
      methyltransferase3A (DNMT3A) promotes neural crest specification by directly
      mediating repression of neural genes like Sox2 and Sox3. DNMT3A is expressed in
      the neural plate border, and its knockdown causes ectopic Sox2 and Sox3
      expression at the expense of neural crest markers. In vivo chromatin
      immunoprecipitation of neural folds demonstrates that DNMT3A specifically
      associates with CpG islands in the Sox2 and Sox3 promoter regions, resulting in
      their repression by methylation. Thus, DNMT3A functions as a molecular switch,
      repressing neural to favor neural crest cell fate.

PMID- 23124062
TI  - Biology of PIWI-interacting RNAs: new insights into biogenesis and function
      inside and outside of germlines.
AB  - PIWI-interacting RNAs (piRNAs) are endogenous small noncoding RNAs that act as
      guardians of the genome, protecting it from invasive transposable elements in the
      germline. Animals lacking piRNA functions show defects in gametogenesis and
      exhibit sterility. Their descendants are also predisposed to inheriting
      mutations. Thus, the piRNA pathway has evolved to repress transposons post
      transcriptionally and/or transcriptionally. A growing number of studies on piRNAs
      have investigated piRNA-mediated gene silencing, including piRNA biogenesis.
      However, piRNAs remain the most enigmatic among all of the silencing-inducing
      small RNAs because of their complexity and uniqueness. Although piRNAs have been
      previously suggested to be germline-specific, recent studies have shown that
      piRNAs also play crucial roles in nongonadal cells. Furthermore, piRNAs have also
      recently been shown to have roles in multigenerational epigenetic phenomena in
      worms. The purpose of this review is to highlight new piRNA factors and novel
      insights in the piRNA world.

PMID- 23124064
TI  - Essential role for Notch signaling in restricting developmental plasticity.
AB  - We report that Notch signaling is essential for the switch from developmental
      plasticity to commitment during Caenorhabditis elegans embryogenesis. The GLP-1
      and LIN-12 Notch receptors act to set a memory state that affects commitment of
      cells arising from the major ectodermal progenitor (AB blastomere) several cell
      divisions later, thereby preventing their forced reprogramming by an endoderm
      determining transcription factor. In contrast to Notch-dependent cell fate
      induction, this activity is autonomous to the AB lineage, is independent of the
      known cell fate-inducing Notch ligands, and requires a putative secreted Notch
      ligand, Delta Serrate Lag-3 (DSL-3). Thus, Notch signaling promotes developmental
      commitment by a mechanism that is distinct from that involved in specifying cell
      fates.

PMID- 23124065
TI  - Brr2p-mediated conformational rearrangements in the spliceosome during activation
      and substrate repositioning.
AB  - Brr2p is one of eight RNA helicases involved in pre-mRNA splicing. Detailed
      understanding of the functions of Brr2p and other spliceosomal helicases has been
      limited by lack of knowledge of their in vivo substrates. To address this, sites
      of direct Brr2p-RNA interaction were identified by in vivo UV cross-linking in
      budding yeast. Cross-links identified in the U4 and U6 small nuclear RNAs
      (snRNAs) suggest U4/U6 stem I as a Brr2p substrate during spliceosome activation.
      Further Brr2p cross-links were identified in loop 1 of the U5 snRNA and near
      splice sites and 3' ends of introns, suggesting the possibility of a previously
      uncharacterized function for Brr2p in the catalytic center of the spliceosome.
      Consistent with this, mutant brr2-G858R reduced second-step splicing efficiency
      and enhanced cross-linking to 3' ends of introns. Furthermore, RNA sequencing
      indicated preferential inhibition of splicing of introns with structured 3' ends.
      The Brr2-G858Rp cross-linking pattern in U6 was consistent with an open
      conformation for the catalytic center of the spliceosome during first-to-second
      step transition. We propose a previously unsuspected function for Brr2p in
      driving conformational rearrangements that lead to competence for the second step
      of splicing.

PMID- 23124066
TI  - The Prp8 RNase H-like domain inhibits Brr2-mediated U4/U6 snRNA unwinding by
      blocking Brr2 loading onto the U4 snRNA.
AB  - The spliceosomal RNA helicase Brr2 catalyzes unwinding of the U4/U6 snRNA duplex,
      an essential step for spliceosome catalytic activation. Brr2 is regulated in part
      by the spliceosomal Prp8 protein by an unknown mechanism. We demonstrate that the
      RNase H (RH) domain of yeast Prp8 binds U4/U6 small nuclear RNA (snRNA) with the
      single-stranded regions of U4 and U6 preceding U4/U6 stem I, contributing to its
      binding. Via cross-linking coupled with mass spectrometry, we identify RH domain
      residues that contact the U4/U6 snRNA. We further demonstrate that the same
      single-stranded region of U4 preceding U4/U6 stem I is recognized by Brr2,
      indicating that it translocates along U4 and first unwinds stem I of the U4/U6
      duplex. Finally, we show that the RH domain of Prp8 interferes with U4/U6
      unwinding by blocking Brr2's interaction with the U4 snRNA. Our data reveal a
      novel mechanism whereby Prp8 negatively regulates Brr2 and potentially prevents
      premature U4/U6 unwinding during splicing. They also support the idea that the RH
      domain acts as a platform for the exchange of U6 snRNA for U1 at the 5' splice
      site. Our results provide insights into the mechanism whereby Brr2 unwinds U4/U6
      and show how this activity is potentially regulated prior to spliceosome
      activation.

PMID- 23124067
TI  - Metabolic compensation of the Neurospora clock by a glucose-dependent feedback of
      the circadian repressor CSP1 on the core oscillator.
AB  - Conidial separation 1 (CSP1) is a global transcription repressor. It is expressed
      under control of the white collar complex (WCC), the core transcription factor of
      the circadian clock of Neurospora. Here we report that the length of the
      circadian period decreases with increasing glucose concentrations in csp1 mutant
      strains, while the period is compensated for changes in glucose concentration in
      wild-type strains. Glucose stimulated CSP1 expression. Overexpression of CSP1
      caused period lengthening and, eventually, complete dampening of the clock
      rhythm. We show that CSP1 inhibits expression of the WHITE COLLAR 1 (WC1) subunit
      of the WCC by repressing the wc1 promoter. Glucose-dependent repression of wc1
      transcription by CSP1 compensated for the enhanced translation of WC1 at high
      glucose levels, resulting in glucose-independent expression of the WCC and,
      hence, metabolic compensation that maintained a constant circadian period. Thus,
      the negative feedback of CSP1 on WC1 expression constitutes a molecular pathway
      that coordinates energy metabolism and the circadian clock.

PMID- 23124069
TI  - An unusual cause of acute appendicitis: Appendiceal endometriosis.
AB  - INTRODUCTION: While endometriosis is a common disorder in women of reproductive
      age, appendiceal endometriosis accounts for less than 1% of all pelvic
      endometriotic lesions. Appendiceal involvement may present as acute appendicitis
      and definitive diagnosis is made by only postoperative histological examination.
      PRESENTATION OF CASE: In this study, we present two cases of female patients who
      underwent an appendectomy presumed diagnosis as acute appendicitis, and a
      histopathological examination of the retrieved specimen revealed appendiceal
      endometriosis. DISCUSSION: Endometriosis is defined as the presence of ectopic
      endometrial tissue outside the lining of the uterine cavity. Gastrointestinal
      endometriosis is observed in 3-37% of all endometriosis cases, whereas
      appendiceal endometriosis accounts for only about 3% of gastrointestinal
      endometriosis. Appendiceal endometriosis is usually asymptomatic, although it
      sometimes causes abdominal cramps, nausea, chronic pelvic pain, lower
      gastrointestinal hemorrhage, intussusception, perforation, or acute appendicitis.
      CONCLUSION: Appendiceal endometriosis is an unusual histopathological finding. A
      preoperative diagnosis is difficult, but this condition should be considered when
      women of childbearing age present with clinical symptoms of acute appendicitis.

PMID- 23124070
TI  - Incidental thyroid papillary carcinoma in a thyroglossal duct cyst - management
      dilemmas.
AB  - INTRODUCTION: Benign thyroglossal duct tract remnants typically thyroglossal duct
      cysts, (TDCs) are one of the commonest congenital childhood midline neck masses.
      Clinical presentation of persistent TDCs in adults is uncommon and the occurrence
      of incidental primary thyroid papillary carcinoma (TPC) in these cysts is rare.
      PRESENTATION OF CASE: We report the case of a 32-year-old female with an
      asymptomatic midline neck mass compatible with a TDC that was excised by
      Sistrunk's procedure. Histopathological examination revealed an incidental
      primary intraluminal TPC arising from the wall of the TDC. DISCUSSION: Management
      dilemmas regarding the roles for total thyroidectomy, regional lymph node
      dissection, radioactive iodine, and suppressive thyroxine therapy are reviewed in
      the context of relevant evidence based literature. CONCLUSION: The occurrence of
      incidental TPC in a TDC is rare. Though Sistrunk's procedure is adequate
      treatment for TDC, based on low, moderate, and high risk stratification,
      recommendations for further management of incidental TPC in TDC is discussed.

PMID- 23124068
TI  - Mechanism for epigenetic variegation of gene expression at yeast telomeric
      heterochromatin.
AB  - Yeast contains heterochromatin at telomeres and the silent mating-type loci
      (HML/HMR). Genes positioned within the telomeric heterochromatin of Saccharomyces
      cerevisiae switch stochastically between epigenetically bistable ON and OFF
      expression states. Important aspects of the mechanism of variegated gene
      expression, including the chromatin structure of the natural ON state and the
      mechanism by which it is maintained, are unknown. To address this issue, we
      developed approaches to select cells in the ON and OFF states. We found by
      chromatin immunoprecipitation (ChIP) that natural ON telomeres are associated
      with Rap1 binding and, surprisingly, also contain known characteristics of OFF
      telomeres, including significant amounts of Sir3 and H4K16 deacetylated
      nucleosomes. Moreover, we found that H3K79 methylation (H3K79me), H3K4me, and
      H3K36me, which are depleted from OFF telomeres, are enriched at ON telomeres. We
      demonstrate in vitro that H3K79me, but not H3K4me or H3K36me, disrupts
      transcriptional silencing. Importantly, H3K79me does not significantly reduce Sir
      complex binding in vivo or in vitro. Finally, we show that maintenance of H3K79me
      at ON telomeres is dependent on transcription. Therefore, although Sir proteins
      are required for silencing, we propose that epigenetic variegation of telomeric
      gene expression is due to the bistable enrichment/depletion of H3K79me and not
      the fluctuation in the amount of Sir protein binding to nucleosomes.

PMID- 23124071
TI  - An atypical site of a retroperitoneal epidermoid cyst in a middle-aged woman.
AB  - INTRODUCTION: Retroperitoneal cysts are rare, usually asymptomatic, abdominal
      lesions. Epidermoid cysts developing in this space usually occur in middle-aged
      women and are incidentally discovered in the presacral region during ultrasound
      examination. Occasionally, cysts may arise from splenic tissue or adrenal glands
      and develop above the presacral area. PRESENTATION OF CASE: We present the
      unusual location of a cyst in the retroperitoneal space in a 41-year-old woman
      admitted to hospital due to detection of a lesion in ultrasound imaging. A CT
      scan confirmed large intra-abdominal cyst. At operation, a large retroperitoneal
      thin-walled cyst with no evident arising point was discovered. Histologic
      analysis revealed epidermoid cyst. DISCUSSION: Our patient presented with giant
      retroperitoneal cyst extending from the subhepatic region to the uterine and
      bladder. To our knowledge, this unusual location in adult has not been previously
      reported in the literature. In our case the lesion was adjacent to inferior vena
      cava and mesenteric vessel which required special attention during preparation
      and was technically demanding. CONCLUSION: Surgery is the gold standard for the
      diagnosis and treatment of retroperitoneal epidermoid cysts. Successful treatment
      of benign retroperitoneal epidermoid cysts depends on appropriate diagnosis,
      careful operative technique, and adequate management of the underlying pathology.

PMID- 23124072
TI  - Innate immunity: Splice-tailored to fit the bug.

PMID- 23124074
TI  - Comparative genome sequence analysis of Sulfolobus acidocaldarius and 9 other
      isolates of its genus for factors influencing codon and amino acid usage.
AB  - In the present study, major constraints for codon and amino acid usage of
      Sulfolobus acidocaldarius, Sulfolobus solfataricus, Sulfolobus tokodali,
      Sulfolobus islandis and 6 other isolates from islandicus species of genus
      Sulfolobus were investigated. Correspondence analysis revealed high significant
      correlation between the major trend of synonymous codon usage and gene expression
      level, as assessed by the "Codon Adaptation Index" (CAI). There is a significant
      negative correlation between Nc (Effective number of codons) and CAI
      demonstrating role of codon bias as an important determinant of codon usage. The
      significant correlation between major trend of synonymous codon usage and GC3s
      (G+C at third synonymous position) indicated dominant role of mutational bias in
      codon usage pattern. The result was further supported from SCUO (synonymous codon
      usage order) analysis. The amino acid usage was found to be significantly
      influenced by aromaticity and hydrophobicity of proteins. However, translational
      selection which causes a preference for codons that are most rapidly translated
      by current tRNA with multiple copy numbers was not found to be highly dominating
      for all studied isolates. Notably, 26 codons that were found to be optimally used
      by genes of S. acidocaldarius at higher expression level and its comparative
      analysis with 9 other isolates may provide some useful clues for further in vivo
      genetic studies on this genus.

PMID- 23124075
TI  - CYP1AI and CYP2E1 gene polymorphisms may increase susceptibility to oral
      submucous fibrosis among betel quid chewers of eastern India.
AB  - Chewing betel quid may release chemical carcinogens including xenobiotics
      resulting in oral malignancy cases preceded by potential malignant lesions and
      conditions - Oral Submucous Fibrosis (OSF) being one of them. The cytochrome
      P4501A1 (CYP1A1) enzyme is central to the metabolic activation of these
      xenobiotics, whereas CYP2E1 metabolizes the nitrosamines and tannins. The present
      study investigated the association of polymorphisms at CYP1A1m1 (T3801C), m2
      (A2455G), and CYP2E1 PstI site (nucleotide 21259) with the risk of OSF. The study
      was conducted on 75 OSF patients and 150 controls from an eastern Indian
      population. The above polymorphisms were analyzed by PCR-RFLP method. Analyses of
      data show that polymorphisms in CYP1A1m2 [OR=8.25 (4.31-15.80)]; CYP1A1m1
      [OR=2.88 (1.57-5.24)] and CYP2E1 PstI site [OR=3.16 (1.10-9.04)] revealed
      significant association with OSF. Our results suggest that polymorphism in CYP1A1
      and CYP2E1 may confer an increased risk for Oral Submucous Fibrosis.

PMID- 23124076
TI  - Differentiation within autologous fibrin scaffolds of porcine dermal cells with
      the mesenchymal stem cell phenotype.
AB  - Porcine mesenchymal stem cells (pMSCs) are an attractive source of cells for
      tissue engineering because their properties are similar to those of human stem
      cells. pMSCs can be found in different tissues but their dermal origin has not
      been studied in depth. Additionally, MSCs differentiation in monolayer cultures
      requires subcultured cells, and these cells are at risk of dedifferentiation when
      implanting them into living tissue. Following this, we attempted to characterize
      the MSCs phenotype of porcine dermal cells and to evaluate their cellular
      proliferation and differentiation in autologous fibrin scaffolds (AFSs). Dermal
      biopsies and blood samples were obtained from 12 pigs. Dermal cells were
      characterized by flow cytometry. Frozen autologous plasma was used to prepare
      AFSs. pMSC differentiation was studied in standard structures (monolayers and
      pellets) and in AFSs. The pMSCs expressed the CD90 and CD29 markers of the
      mesenchymal lineage. AFSs afforded adipogenic, osteogenic and chondrogenic
      differentiation. The porcine dermis can be proposed to be a good source of MSCs
      with adequate proliferative capacity and a suitable expression of markers. The
      pMSCs also showed optimal proliferation and differentiation in AFSs, such that
      these might serve as a promising autologous and implantable material for use in
      tissue engineering.

PMID- 23124077
TI  - miR-101 is down-regulated by the hepatitis B virus x protein and induces aberrant
      DNA methylation by targeting DNA methyltransferase 3A.
AB  - The hepatitis B virus x (HBx) protein has been implicated in HBV-related
      hepatocellular carcinoma (HCC) pathogenesis. However, whether HBx regulates miRNA
      expression that plays important roles in gene regulation during
      hepatocarcinogenesis remains unknown. The expression of microRNA-101 (miR-101) in
      HBV-related HCC tissues and HCC cells was evaluated by real-time PCR. The direct
      target of miR-101, DNA methyltransferase 3A (DNMT3A), was identified in silico
      and validated using a 3'-UTR reporter assay. miR-101 was functionally
      characterized in cells with transiently altered miR-101 expression. HBx
      expression was found to have a significant inverse correlation with miR-101
      expression in HBx-expressing HepG2 compared to control HepG2 cells. miR-101
      expression was frequently down-regulated in HBV-related HCC tissues compared to
      adjacent noncancerous hepatic tissues and had a significant inverse correlation
      with DNMT3A expression in HBV-related HCCs. Further characterization of miR-101
      revealed that it negatively regulated DNA methylation partly through targeting
      DNMT3A. HBx-mediated miR-101 down-regulation and DNMT3A up-regulation supported
      the enhanced DNA methylation of several tumor-suppressor genes in HBx-expressing
      cells. Our studies demonstrating the deregulation of miR-101 expression by HBx
      may provide novel mechanistic insights into HBV-mediated hepatocarcinogenesis and
      identify a potential miRNA-based targeted approach for treating HBV-related HCC.

PMID- 23124078
TI  - Expression of the Foxi2 and Foxi3 transcription factors during development of
      chicken sensory placodes and pharyngeal arches.
AB  - Foxi2 and Foxi3 are members of the Foxi class of Forkhead transcription factors.
      The Foxi transcription factor family has been shown to play roles in the
      development of the inner ear and pharyngeal arch derivatives in zebrafish. We
      describe the expression of Foxi2 and Foxi3 in chicken embryos during the first
      three days of embryonic development. Foxi3 is initially expressed broadly in the
      pre-placodal ectoderm surrounding the neural plate, which will give rise to all
      craniofacial sensory organs. It then becomes restricted to a region immediately
      anterior to the first pair of somites that will give rise to the otic and
      epibranchial placodes, before becoming down-regulated from this region and
      restricted to the ectoderm and endoderm of the pharyngeal arches. In contrast,
      Foxi2 is initially expressed broadly in cranial ectoderm with the striking
      exception of the otic placode, and ultimately becomes restricted to pharyngeal
      arch ectoderm. These expression patterns provide an insight into the roles of
      these transcriptional regulators during the development of the inner ear and
      pharyngeal arch derivatives.

PMID- 23124073
TI  - The role of the IAP E3 ubiquitin ligases in regulating pattern-recognition
      receptor signalling.
AB  - An inflammatory response is initiated when innate immune pattern-recognition
      receptors (PRRs) expressed by different cell types detect constituents of
      invading microorganisms and endogenous intracellular molecules released by dying
      cells. The intracellular cascades activated by PRRs induce the expression and
      maturation of inflammatory molecules that coordinate the removal of the
      infectious agents and of the infected or damaged cells. In this Review, we
      discuss the findings implicating members of the inhibitor of apoptosis protein
      (IAP) family in the ubiquitylation-dependent regulation of PRR signalling.
      Understanding the role of IAPs in innate immunity may open new therapeutic
      perspectives for the treatment of PRR-dependent inflammatory diseases.

PMID- 23124079
TI  - Rapid synthesis of oligomannosides with orthogonally protected monosaccharides.
AB  - We developed a facile synthesis to yield orthogonally protected mannose building
      blocks with high overall yields. The protection/glycosylation steps can be
      carried out in a successive manner without purification of intermediate products.
      This developed synthesis led to formation of linear/branched tri-, penta- and
      heptasaccharides.

PMID- 23124080
TI  - [Th17 cells and skin diseases].
AB  - Th17 cells have crucial functions in host defense, and dysregulated Th17
      responses mediate a variety of autoimmune and inflammatory conditions. Th17 cells
      coexpress IL-22, and its receptor is expressed on epidermal keratinocytes. IL-17
      and /or IL-22 induce the production of certain cytokines, chemokines and
      antimicrobial peptides by keratinocytes, and its cooperation with IL-22 has been
      documented. Recent findings have suggested that Th17 cells profoundly participate
      in the pathogenesis of certain skin disorders, in particular, psoriasis. The
      involvement of Th17 cells has also been shown in allergen-specific immune
      responses. The percentage of Th17 cells is increased in peripheral blood of
      patients with atopic dermatitis (AD) and associated with the severity of AD. Drug
      eruption is another disease where circulating Th17 cells are increased.

PMID- 23124081
TI  - [MAIT cells in autoimmunity].
AB  - Mucosal associated invariant T (MAIT) cells are restricted by a nonpolymorphic
      MHC-related molecule-1 (MR1), and express an invariant TCRalpha chain: Valpha7.2
      Jalpha33 in humans and Valpha19-Jalpha33 in mice. MAIT cells are selected in the
      thymus, but, interestingly, MAIT cells require B cells as well as commensal flora
      for their peripheral expansion. Bourhis et al demonstrated that MAIT cells
      display antimicrobial capacity. Both human and mouse MAIT cells have been shown
      to be activated by Escherichia coli-infected antigen presenting cells in an MR1
      dependent manner. MAIT cells show a protective role against Mycobacteriu
      abscessus or E. coli infections in mice. Human MAIT cells are capable of
      producing IFNgamma and IL-17 and are found in Mycobacterium tuberculosis-infected
      lung tissues. Thus, MAIT cells play an antimicrobial function under these
      infectious conditions. MAIT cells play a protective role against autoimmune
      encephalomyelitis (EAE), an animal model of human multiple sclerosis (MS),
      whereas they play a pathogenic role in murine models of arthritis. In patients
      with autoimmune diseases, the frequency of MAIT cells in peripheral blood was
      significantly reduced. The frequency of MAIT cells reflected the disease activity
      in MS patients, suggesting the involvement of MAIT cells in the regulation of
      autoimmune diseases.

PMID- 23124082
TI  - [Development, competition and plasticity of the T-lymph cells in inflammatory
      bowel disease].
AB  - The hypothesis of helper T (T(h))1/T(h)2 cytokine balance was often invoked to
      explain the development of inflammatory diseases, including inflammatory bowel
      diseases (IBD). Recently, a newly identified class of regulatory T cells (Tregs),
      which suppress inflammation and helper T(Th)17 cells, which produce Th17 family
      cytokines has been recognized as an essential subpopulation in the development of
      almost all kinds of human and animal inflammatory diseases. T cell subsets can
      act as terminally differentiated lineages, but they have been increasingly noted
      to demonstrated plasticity, depending on their surrounding such as intestinal
      microbiota. Th17 cells and Th1 cells coordinate to play a critical role in the
      formation of inflammatory bowel diseases. We showed Th1 and Th17 cells are
      competitive in lymphopenic mice, and that their orchestration results in a merged
      clinical phenotype of the two types of murine colitis. We also showed that Th17
      and Th17/Th1 cells become colitogenic alternative Th1 cells via Th17, Th17/Th1,
      and Th1-like cells, independently of classical Th1 cells. Treg cells suppress
      this pathway, resulting in accumulation of Th17 and Th17/Th1 cells. Here we
      review T cell development including their plasticity and recent advances in the
      study of such Treg cells and Th17 cells in the pathogenesis of IBD.

PMID- 23124083
TI  - [The regulation of antitumor immune responses by helper T cells--From the bench
      research to the discovery of H/K-HELP cancer vaccine].
AB  - During past decades, cancer vaccine therapy has been focused on only the
      activation of CTL, but its therapeutic effect was not successful though long SD
      was induced. The failure of cancer vaccine is derived from (i) the existence of a
      strong tumor escape mechanisms and (ii) the ignorance of helper T cell
      activation. We have proposed that Th1-dominant immunity played a critical role
      for overcoming immunosuppressive tumor-escape mechanisms to induce tumor-specific
      CTL, which are essential for the complete cure of tumor and prevention of tumor
      recurrence. To apply these basic findings, we started a clinical trial of a novel
      cancer vaccine/cell therapy (Th1 cell therapy) using H/K-HELP of MAGE-A4 or
      Survivin cancer antigen. In phase I study, H/K-HELP consisted of both killer and
      helper epitopes and Th1 adjuvants (OK-432 and Montanide) were subcutaneously
      administered into cancer patients 4 times at 2 wks intervals. Both MAGE-A4-H/K
      HELP and Survivin-H/K-HELP cancer vaccine induced cancer-specific Th1 and Tc1
      immune responses and cancer-specific C-fixing antibodies (IgG1 and IgG3) in
      cancer patients. Moreover, Survivin-H/K-HELP vaccination induced a complete
      regression of chemo and radio-resistant lateral deep cervical node recurrence of
      triple-negative breast cancer. H/K-HELP vaccination with Th1 adjuvants or its
      combination with Th1 cells will become a promising cancer vaccine/cell therapy of
      human cancer.

PMID- 23124084
TI  - [Regulatory T cells and regulatory NK cells play essential roles for maintenance
      of pregnancy].
AB  - During pregnancy, semiallograftic fetus is allowed to grow without being rejected
      by the maternal immune system. Recent data show that paternal antigen specific-
      or male antigen HY specific-regulatory T cells (Treg) increase during pregnancy.
      Seminal plasma is necessary for the accumulation of Treg cells in uterine
      draining lymph modes just before implantation, and in uterus just after
      implantation. It has been reported that decreased number of Treg cells in
      peripheral blood or pregnant uterus in abortion or preeclampsia. In human and
      rodent pregnant uterus, NK cells are the major population (~80%) of lymyhocytes,
      we have reported that CD25(+) NK cells increase in mouse pregnant uterus, and
      these NK cells produce immunoregulatory cytokines such as IL-10 and TGF-beta.
      They inhibit the expression of MHC class II antigen on dendritic cells and
      inhibit the cytotoxic T cell induction, suggesting that these NK cells have an
      ability for immunoregulation. Both Treg cells and regulatory NK cells play
      important roles for maintenance of pregnancy.

PMID- 23124085
TI  - [A case of Sjogren syndrome suspected, rheumatoid arthritis and Behcet's disease
      complicated with cochlear nerve and trigeminal nerve disorders].
AB  - We described a patient with secondary Sjogren's syndrome suspected showing
      multiple cranial neuropathies at the different time. A 68-year old woman has been
      treated as rheumatoid arthritis since 1963. In 2001, she was also diagnosed with
      Sjogren's syndrome suspected. Afterward, abducent and trigeminal neuropathies and
      uveites occurred. This case is important to insight into the cranial neuropathy
      with Sjogren's syndrome.

PMID- 23124087
TI  - [A case of calcinomatous polyarthritis presenting rheumatoid arthritis-like
      polyarthritis as the initial symptom of gastric cancer].
AB  - We report a case of calcinomatous polyarthritis presenting rheumatoid arthritis
      like polyarthritis as the initial symptom of gastric cancer. A 79-year-old male
      visited to our hospital with complaint of pain and swelling of multiple joints
      including bilateral hands, bilateral knees, elbows and small joints of fingers.
      He also complained of neck and back stiffness. Both of rheumatoid factor test and
      anti-cyclic citrullinated peptide antibody were negative. Non-steroidal anti
      inflammatory drug did not relieve his arthritic pain. He showed anorexia, body
      weight loss and was anemic. Upper gastrointestinal endoscopic evaluation
      demonstrated a gastric cancer. The patient underwent subtotal gastrectomy. Within
      1 week after the subtotal gastrectomy, both polyarthritis and stiffness started
      to improve. The polyarthritis in this case was diagnosed as calcinomatous
      plyarthritis for its features. Paraneoplastic rheumatism remains a rare event,
      but knowledge of it is essential for early diagnosis of underlying cancer.

PMID- 23124086
TI  - [A case of rheumatoid arthritis complicated with deteriorated interstitial
      pneumonia after the administration of abatacept].
AB  - We report a case of rheumatoid arthritis (RA) complicated with interstitial
      pneumonia that deteriorated after the administration of abatacept. A 55-year-old
      man developed RA and interstitial pneumonia. Although interstitial pneumonia was
      improved by high-dose glucocorticoids, various disease-modifying antirheumatic
      drugs including infliximab were ineffective for his arthritis. Tacrolimus was
      effective but was discontinued due to refractory itching and diarrhea. After 2
      months, he was registered on the Phase III trial of abatacept in Japan because of
      worsening of arthritis. From 2 days after the abatacept administration, frothy
      sputum frequently appeared, but sputum culture was negative. On 13 days after the
      administration, the interstitial shadow was deteriorated by chest CT as compared
      with that of 2 months before, and he was dropped out from the trial. On 27 days
      after the administration, the dose of prednisolone was increased from 2 to 10
      mg/day for his arthritis. On 44 days after the administration, the interstitial
      pneumonia improved. Abatacpet might be the cause of the deterioration of the
      interstitial pneumonia, but other possibilities such as discontinuation of
      tacrolimus, flare-up of RA itself or viral infection should be considered. This
      is the first report of deteriorated interstitial pneumonia after the abatacept
      administration in the literature. Further cases are needed to identify the
      relation between abatacept and interstitial pneumonia, however this possibility
      should be always kept in mind when we use abatacept.

PMID- 23124088
TI  - Toxicity effects of short term diesel exhaust particles exposure to human small
      airway epithelial cells (SAECs) and human lung carcinoma epithelial cells (A549).
AB  - In this study, confocal Raman spectroscopy, atomic force microscope (AFM) and
      multiplex ELISA were applied to analyze the biophysical responses (biomechanics
      and biospectroscopy) of normal human primary small airway epithelial cells
      (SAECs) and human lung carcinoma epithelial A549 cells to in vitro short term DEP
      exposure (up to 2h). Raman spectra revealed the specific cellular biomolecular
      changes in cells induced by DEP compared to unexposed control cells. Principal
      component analysis was successfully applied to analyze spectral differences
      between control and treated groups from multiple individual cells, and indicated
      that cell nuclei are more sensitive than other cell locations. AFM measurements
      indicated that 2h of DEP exposure induced a significant decrease in cell
      elasticity and a dramatic change in membrane surface adhesion force. Cytokine and
      chemokine production measured by multiplex ELISA demonstrated DEP-induced
      inflammatory responses in both cell types.

PMID- 23124089
TI  - Columbamine suppresses the proliferation and neovascularization of metastatic
      osteosarcoma U2OS cells with low cytotoxicity.
AB  - Osteosarcoma is one of the most common malignant bone tumors in children and
      adolescents. Although extensive efforts have been made in anti-osteosarcoma
      therapy in recent decades, there are no effective low-toxicity drugs for treating
      patients with metastatic osteosarcoma. Hence, potent anti-metastatic osteosarcoma
      drugs are highly desired. In this study, we explored novel small molecular anti
      metastatic osteosarcoma agents and found that columbamine (COL), an active
      component of the herb Coptis chinensis, inhibited the proliferation and
      neovascularization of metastatic osteosarcoma U2OS cells. COL effectively
      suppressed U2OS cell proliferation in vitro with an IC(50) of 21.31+/-0.38MUM,
      with low cytotoxicity. Mechanistic studies revealed that COL induces cell cycle
      arrest at the G2/M transition, which is associated with attenuating CDK6 gene
      expression and diminishing STAT3 phosphorylation. COL did not significantly
      promote U2OS cell apoptosis at any of the dosages tested. Additionally, COL
      inhibited U2OS cell-mediated neovascularization, which was accompanied by the
      down-regulation of matrix metalloproteinase (MMP) 2 expression and reduction of
      cell migration, adhesion, and invasion. Taken together, our data show that COL
      exerts anti-proliferative and anti-vasculogenic effects on metastatic human
      osteosarcoma U2OS cells with low toxicity. These results warrant further
      investigation of COL as a potential anti-osteosarcoma and anti-cancer drug.

PMID- 23124090
TI  - A microfluidic chip for axonal isolation and electrophysiological measurements.
AB  - A microfluidic chip for culturing neurons and spatially isolating axons from
      somas is presented for use with visually guided whole-cell electrophysiological
      measurements. A modular design consisting of detachable and re-sealable layers is
      used to satisfy the requirements of both long-term neuron culturing as well as
      electrophysiological measurements. Whole cell patch clamp recordings indicate
      functional viability of neurons with isolated axons. Fluidic isolation was used
      to achieve asymmetric lentiviral infection of neurons on a single side reservoir.
      Neurons were asymmetrically infected with lentiviruses expressing the light
      activated cationic channel channelrhodopsin-2. Light-evoked excitatory
      postsynaptic responses were detected by whole cell recordings of neurons on the
      uninfected side showing functional synaptic connectivity between the two isolated
      but axonally connected sides of the device.

PMID- 23124091
TI  - Novel nucleolar isolation method reveals rapid response of human nucleolar
      proteomes to serum stimulation.
AB  - The nucleolus is the location of ribosomal biogenesis, and plays crucial
      regulatory roles in nuclear responses to stress. Here, we report a new and
      improved nucleolar isolation method, which is simpler and more efficient than the
      traditional method. The purity of nucleoli obtained by using the new protocol is
      comparable to that by using the classical method, as judged by electron
      microscopy, Western blotting and SILAC-based quantitative proteomics. Moreover,
      the improved efficiency of cell harvesting in the new method, biochemical events
      in the nucleolus could be "frozen" and captured at precisely controlled time
      points. Time-lapse nucleolar proteomics after serum stimulation in HeLa cell
      revealed for the first time that some nucleolar proteins respond to serum
      stimulation within a time period as short as the first 5 min of serum re
      stimulation. Proteins involved in ribosomal biogenesis and in DNA damage repair
      are among the most dynamic proteins during the first 10 min after serum
      replenishment. Notably, the proliferation marker Ki-67 is also found to enter the
      nucleolus after serum replenishment. To our knowledge, this is the first study
      that demonstrates such fast responses in the nucleolus, further confirming the
      rapid plasticity of this organelle.

PMID- 23124092
TI  - Learning deficits in an odor reward-task induced by parafascicular thalamic
      lesions are ameliorated by pretraining D-cycloserine in the prelimbic cortex.
AB  - We investigated whether the N-methyl-D-aspartate (NMDA) receptor partial agonist
      D-cycloserine (DCS) infused into the prelimbic cortex (PLC) would reverse the
      learning deficits caused by bilateral excitotoxic lesions of the parafascicular
      nucleus (PFn) in an odor discrimination task (ODT). Rats with PFn lesions
      received a bilateral infusion of DCS (10 MUg/side) into the PLC 20 min before ODT
      acquisition. The task retention was evaluated in a drug-free test carried out 24
      h later. DCS significantly attenuated the PFn lesion-induced deficits as measured
      by both latency to nose-poke the rewarded odor and number of errors committed
      during ODT acquisition and retention. Therefore, DCS may be an enhancing memory
      treatment in animal models of cognitive impairment, such as PFn-lesioned rats.
      The PFn contribution to learning and memory may possibly be linked to its role in
      the modulation of glutamatergic PLC activity.

PMID- 23124093
TI  - Targeted protein identification, quantification and reporting for high-resolution
      nanoflow targeted peptide monitoring.
AB  - Mass spectrometry-based targeted proteomic assays are experiencing a surge in
      awareness due to the diverse possibilities arising from the re-application of
      traditional LC-SRM technology. The FDA-approved quantitative LC-SRM-pipeline in
      drug discovery motivates the use to quantitatively validate putative proteomic
      biomarkers. However, complexity of biological specimens bears a huge challenge to
      identify, in parallel, specific peptides and proteins of interest from large
      biomarker candidate lists. Methods have been devised to increase scan speeds,
      improve detection specificity and verify quantitative SRM-features. In contrast,
      high-resolution mass spectrometers could be used to improve reliability and
      precision of targeted proteomics assays. Here, we present a new method for
      identifying, quantifying and reporting peptides in high-resolution targeted
      proteomics experiments performed on an orbitrap hybrid instrument using stable
      isotope-labeled internal reference peptides. This high precision targeted peptide
      monitoring (TPM) method has unique advantages over existing techniques, including
      the need to only detect the most abundant product ion of a given target for
      confident peptide identification using a scoring function that evaluates assay
      performance based on 1) m/z-mass accuracy, 2) retention time accuracy of observed
      species relative to prediction, and 3) retention time accuracy relative to
      internal reference peptides. Further, we show management of multiplexed precision
      TPM-assays using sentinel peptide standards. This article is part of a Special
      Issue entitled: From protein structures to clinical applications.

PMID- 23124094
TI  - Defected red blood cell membranes and direct correlation with the uraemic milieu:
      the connection with the decreased red blood cell lifespan observed in
      haemodialysis patients.
AB  - Together with impaired production of erythropoietin and iron deficiency, the
      decreased lifespan of red blood cells (RBCs) is a main factor contributing to the
      chronic anaemia observed in haemodialysis (HD) patients. Atomic force microscopy
      is employed in this work to thoroughly survey the membrane of intact RBCs (iRBCs)
      of HD patients in comparison to those of healthy donors, aiming to obtain direct
      information on the structural status of RBCs that can be related to their
      decreased lifespan. We observed that the iRBC membrane of the HD patients is
      overpopulated with extended circular defects, termed 'orifices', that have
      typical dimension ranging between 0.2 and 1.0 MUm. The 'orifice' index-that is,
      the mean population of 'orifices' per top membrane surface-exhibits a pronounced
      relative increase of order 54 +/- 12% for the HD patients as compared to healthy
      donors. Interestingly, for the HD patients, the 'orifice' index, which relates to
      the structural status of the RBC membrane, correlates strongly with urea
      concentration, which is a basic index of the uraemic milieu. Thus, these results
      indicate that the uraemic milieu downgrades the structural status of the RBC
      membrane, possibly triggering biochemical processes that result in their
      premature elimination from the circulation. This process could decrease the
      lifespan of RBCs, as observed in HD patients.

PMID- 23124095
TI  - Peri-ictal network dynamics of spike-wave discharges: phase and spectral
      characteristics.
AB  - PURPOSE: The brain is a highly interconnected neuronal assembly in which network
      analyses can greatly enlarge our knowledge on seizure generation. The cortico
      thalamo-cortical network is the brain-network of interest in absence epilepsy.
      Here, network synchronization is assessed in a genetic absence model during 5 s
      long pre-ictal->ictal transition periods. METHOD: 16 male WAG/Rij rats were
      equipped with multiple electrodes targeting layer 4 to 6 of the somatosensory
      cortex, rostral and caudal RTN, VPM, anterior-(ATN) and posterior (Po) thalamic
      nucleus. Local field potentials measured during pre-ictal->ictal transition and
      during control periods were subjected to time-frequency and pairwise phase
      consistency analysis. RESULTS: Pre-ictally, all channels showed spike-wave
      discharge (SWD) precursor activity (increases in spectral power), which were
      earliest and most pronounced in the somatosensory cortex. The caudal RTN
      decoupled from VPM, Po and cortical layer 4. Strong increases in synchrony were
      found between cortex and thalamus during SWD. Although increases between cortex
      and VPM were seen in SWD frequencies and its harmonics, boarder spectral
      increases (6-48Hz) were seen between cortex and Po. All thalamic nuclei showed
      increased phase synchronization with Po but not with VPM. CONCLUSION: Absence
      seizures are not sudden and unpredictable phenomena: the somatosensory cortex
      shows highest and earliest precursor activity. The pre-ictal decoupling of the
      caudal RTN might be a prerequisite of SWD generation. Po nucleus might be the
      primary thalamic counterpart to the somatosensory-cortex in the generation of the
      cortico-thalamic-cortical oscillations referred to as SWD.

PMID- 23124096
TI  - Overexpression of DYRK1A inhibits choline acetyltransferase induction by oleic
      acid in cellular models of Down syndrome.
AB  - Histological brain studies of individuals with DS have revealed an aberrant
      formation of the cerebral cortex. Previous work from our laboratory has shown
      that oleic acid acts as a neurotrophic factor and induces neuronal
      differentiation. In order to characterize the effects of oleic acid in a cellular
      model of DS, immortalized cell lines derived from the cortex of trisomy Ts16
      (CTb) and normal mice (CNh) were incubated in the absence or presence of oleic
      acid. Oleic acid increased choline acetyltransferase expression (ChAT), a marker
      of cholinergic differentiation in CNh cells. However, in trisomic cells (CTb
      line) oleic acid failed to increase ChAT expression. These results suggest that
      the overdose of specific genes in trisomic lines delays differentiation in the
      presence of oleic acid by inhibiting acetylcholine production mediated by ChAT.
      The dual-specificity tyrosine (Y) phosphorylation-regulated kinase 1A (DYRK1A)
      gene is located on human chromosome 21 and encodes a proline-directed protein
      kinase. It has been proposed that DYRK1A plays a prominent role in several
      biological functions, leading to mental retardation in DS patients. Here we
      explored the potential role of DYRK1A in the modulation of ChAT expression in
      trisomic cells and in the signaling pathways of oleic acid. Down-regulation of
      DYRK1A by siRNA in trisomic CTb cells rescued ChAT expression up to levels
      similar to those of normal cells in the presence of oleic acid. In agreement with
      these results, oleic acid was unable to increase ChAT expression in neuronal
      cultures of transgenic mice overexpressing DYRK1A. In summary, our results
      highlight the role played by DYRK1A in brain development through the control of
      ChAT expression. In addition, the overexpression of DYRK1A in DS models prevented
      the neurotrophic effect of oleic acid, a fact that may account for mental
      retardation in DS patients.

PMID- 23124097
TI  - High-resolution imaging of entire organs by 3-dimensional imaging of solvent
      cleared organs (3DISCO).
AB  - One goal in neuroscience is to dissect neuronal connections within the nervous
      system in health and disease. To accomplish this, neurons and their extensions
      need to be imaged and followed in the entire brain and spinal cord. While non
      invasive imaging methods such as MRI do not have sufficient resolution to trace
      individual cells, standard histology - serial tissue sectioning and tracing in
      consecutive sections - is time consuming and prone to mistakes. Here, we review
      an alternative method called "3D imaging of solvent cleared organs" or "3DISCO"
      that can achieve high-resolution imaging of neuronal connections in several
      millimeters of depth without tissue sectioning. 3DISCO is fast: imaging of an
      entire organ at a cellular resolution can be completed within a few hours. 3DISCO
      is versatile: it is applicable to various tissues including the spinal cord,
      brain, lung, mammary glands, immune organs and tumors; it can be executed using
      various microscopy techniques, including light-sheet, widefield epifluorescence,
      confocal, 2-photon, light microscopy and optical coherent tomography. Here, we
      review the application of 3DISCO along with other popular clearing and imaging
      methods, their limitations and the obstacles that remain.

PMID- 23124098
TI  - Heme oxygenase-1-mediated reactive oxygen species reduction is involved in the
      inhibitory effect of curcumin on lipopolysaccharide-induced monocyte
      chemoattractant protein-1 production in RAW264.7 macrophages.
AB  - Monocyte chemoattractant protein 1 (MCP-1) is a CC chemokine which stimulates
      mononuclear leukocytes and is significant in the pathogenesis of inflammatory
      disease. Curcumin, extracted from Curcumae longae, has been shown to possess anti
      inflammatory activity, in inflammation associated with the induction of MCP-1
      expression. However, the underlying mechanisms involved in the effect of curcumin
      on MCP-1 expression remain unclear. In the current study, we investigated the
      effect of curcumin on the production of MCP-1 induced by lipopolysaccharide (LPS)
      in macrophages and the possible mechanisms involved. The results revealed that
      curcumin decreased MCP-1 production in a concentration-dependent manner and
      reduced the generation of reactive oxygen species (ROS) induced by LPS in
      RAW264.7 macrophages. Additionally, zinc protoporphyrin, a heme oxygenase-1 (HO
      1) inhibitor, blocked the inhibitory effect of curcumin on the LPS-induced MCP-1
      expression. The exposure of cells to curcumin was found to enhance HO-1
      expression. Furthermore, additional experiments indicated that the inhibitory
      effect of curcumin on LPS-induced MCP-1 expression was significantly attenuated
      in the presence of N-acetylcysteine (an effective ROS scavenger). The results
      presented in our study suggest that curcumin enhances the expression of HO-1 to
      reduce the LPS-induced production of ROS, which leads to the inhibition of MCP-1
      expression in RAW264.7 macrophages. 

PMID- 23124099
TI  - Vascular aging:  shifting the paradigm of risk assessment and reduction in
      hypertension.

PMID- 23124100
TI  - Evaluating interventions to reduce central aortic pressure, arterial stiffness
      and morbidity--mortality.
AB  - Arterial aging is associated with a progressive increase in aortic stiffening,
      which results in a rise in central aortic pressures. Traditionally, blood
      pressure (BP)-lowering therapy has been directed at brachial rather than central
      pressures. However, a key contemporary question is whether this strategy is
      optimal in reducing aortic pressure and aortic stiffness, and whether specific
      treatment strategies might be preferred to reduce the process of arterial aging.
      This review examines current evidence that BP-lowering treatments can
      differentially affect aortic pressure and stiffness parameters relative to
      brachial BP. There is now unequivocal evidence that different treatment regimens
      can differentially affect BP in the central aorta relative to brachial BP, and
      emerging evidence of BP-independent differential drug effects on arterial
      stiffness. A remaining challenge is to link any potentially favorable changes in
      aortic pressure and/or stiffness to improvements in morbidity and mortality over
      and above those expected from conventional BP lowering.

PMID- 23124101
TI  - Progress towards identifying biomarkers of vascular aging for total
      cardiovascular risk prediction.
AB  - Although several scoring systems for cardiovascular risk prediction are valuable
      in the assessment and management of asymptomatic individuals and patients,
      differences between predicted and actual events do exist. The concept of vascular
      aging as a cumulative measure of the impact of cardiovascular risk factors on the
      arterial wall has the potential to gauge an individual's overall cardiovascular
      risk. In this context, candidate arterial biomarkers, apart from proving an
      incremental predictive value over and above traditional risk factors, must
      fulfill stringent criteria in order to be integrated into clinical practice;
      these include calibration, discrimination and reclassification. Current evidence
      suggests that arterial stiffness fulfills the criteria for a biomarker of
      vascular aging, whereas central hemodynamics and carotid intima-media thickness
      are close. Endothelial function, although a valuable research tool, has
      shortcomings in terms of risk prediction, largely dependent on the methodological
      approach, which may make it less desirable as a biomarker.

PMID- 23124102
TI  - Defining vascular aging and cardiovascular risk.
AB  - Whereas vascular aging has been identified as an emerging cardiovascular risk
      factor, definitions of 'normal' and 'early' vascular aging (EVA) and their
      precise relationship with cardiovascular risk are currently equivocal. The
      present review discusses the concept of vascular aging; that structural and
      functional changes occur in the large arteries with aging; and EVA; that such age
      associated changes are accelerated in individuals at increased cardiovascular
      risk; and their metrics; indeed, in order to provide a definition of when EVA
      occurs in clinical practice, reference values of normal and accelerated vascular
      aging are needed. Due to the complex nature of age-associated changes in the
      large arteries described above, there are different parameters relating to
      vascular aging which can be measured. These broadly include aortic and carotid
      stiffening; aortic and carotid lumen dilation; endothelial dysfunction (usually
      measured via brachial flow-mediated dilatation); and carotid intima-media
      thickness.

PMID- 23124103
TI  - Anti-atherogenic effects of the combination therapy with olmesartan and
      azelnidipine in diabetic apolipoprotein E-deficient mice.
AB  - Many studies have aimed to identify anti-atherogenic agents in cardiovascular
      medicine.  We have recently demonstrated that the combination therapy with
      olmesartan (OLM), an angiotensin II receptor blocker, and azelnidipine (AZL), a
      dihydroprydine calcium-channel blocker, improves endothelial function in diabetic
      Apolipoprotein-deficient (ApoE(-/-)) mice.  In the present study, we examined
      whether this combination therapy also inhibits atherosclerosis in mice.  We used
      male control and streptozocin-induced diabetic ApoE(-/-) mice.  Diabetic ApoE(-/
      ) mice were orally treated for 5 weeks with vehicle (Untreated), OLM (30
      mg/kg/day), AZL (10 mg/kg/day), their combination (OLM+AZL), or hydralazine (HYD,
      5 mg/kg/day) as an antihypertensive control.  At 5 weeks, systolic blood pressure
      was significantly elevated in Untreated but was normalized in OLM+AZL and HYD. 
      The atherosclerosis area in the thoracic aorta, perivascular fibrosis and medial
      thickness of the coronary arteries were increased in Untreated and were
      ameliorated in OLM+AZL but not in HYD.  Staining with a fluorescent probe
      dihydroethidium showed that production of reactive oxygen species was increased
      in Untreated, and ameliorated in OLM+AZL.  Consistent with these findings,
      macrophage infiltration in the kidney and the expression of receptor for advanced
      glycation end-products in the heart, kidney and liver were increased in Untreated
      and were all ameliorated in OLM+AZL, associated with up-regulation of endothelial
      NO syntheses (eNOS).  In conclusion, the combination therapy with OLM and AZL
      exerts anti-atherogenic effect in diabetic ApoE(-/-) mice through suppression of
      oxidative stress and activation of eNOS, independent of its blood pressure
      lowering effects.  Clinically, this combination therapy may be useful for
      patients with hypertension, hyperlipidemia and diabetes.

PMID- 23124104
TI  - Injectable PLGA/hydrocortisone formulation produced by continuous supercritical
      emulsion extraction.
AB  - The objective of the present study was to develop an anti-inflammatory prolonged
      action formulation for local injection in prefilled syringes. Hydrocortisone
      acetate (HA) was selected as a model corticosteroid drug to be incorporated in
      poly(lactic-co-glycolic) (PLGA) microspheres. The formulation was obtained by
      supercritical emulsion extraction in continuous operation layout (SEE-C) to test
      the process robustness for a continuous industrial production. PLGA/HA
      microspheres with mean sizes between 1 MUm (SD+/-0.20) and 5 MUm (SD+/-1.45) were
      obtained when operating at 80 bar and 38  degrees C with a L/G ratio of 0.1 in
      the counter-current tower. The produced microdevices showed excellent
      encapsulation efficiencies between 75% and 80%, depending on the emulsion
      formulations tested, and different sustained release in the range of 6-15 days.
      In dependence of the different emulsion (single or double) processed by SEE-C,
      different products can be obtained according to the therapeutic requests. SEE-C
      confirms to be an innovative and flexible technology for biopolymer microdevices
      production, coupling the efficiency of continuous operation to the easy process
      scalability.

PMID- 23124105
TI  - The use of acoustic spectroscopy in the characterisation of ternary phase
      diagrams.
AB  - This study shows novel and interesting applications of acoustic spectroscopy for
      characterisation of ternary systems such as isopropylmiristate (IPM)/polysorbate
      80 (T)/water (W). Particle size and microrheological extensional moduli (i.e. G'
      and G") of different systems were determined by means of acoustic parameters such
      as sound attenuation and speed. Electric conductivity was also measured using the
      same instrument. The ultrasonic profile in terms of attenuation and sound speed
      in the megahertz frequency range, allowed the characterisation of the different
      zones of the ternary diagram such as microemulsion, emulsion and gel zones, as
      well as the evaluation of water state and particle size. This last parameter is a
      very effective tool in quantifying the phase transitions of systems and
      understanding which system is formed in any phase diagram zone. In fact, it is
      possible to analyse samples without dilution and despite their degree of
      turbidity, allowing complete characterisation of both properties and structure.

PMID- 23124106
TI  - Dry powder inhalation of macromolecules using novel PEG-co-polyester
      microparticle carriers.
AB  - This study investigated optimizing the formulation parameters for encapsulation
      of a model mucinolytic enzyme, alpha-chymotrypsin (alpha-CH), within a novel
      polymer; poly(ethylene glycol)-co-poly(glycerol adipate-co-omega
      pentadecalactone), PEG-co-(PGA-co-PDL) which were then applied to the formulation
      of DNase I. alpha-CH or DNase I loaded microparticles were prepared via spray
      drying from double emulsion (w(1)/o/w(2)) utilizing chloroform (CHF) as the
      organic solvent, L-leucine as a dispersibility enhancer and an internal aqueous
      phase (w(1)) containing PEG4500 or Pluronic((r)) F-68 (PLF68). alpha-CH released
      from microparticles was investigated for bioactivity using the azocasein assay
      and the mucinolytic activity was assessed utilizing the degradation of mucin
      suspension assay. The chemical structure of PEG-co-(PGA-co-PDL) was characterized
      by (1)H NMR and FT-IR with both analyses confirming PEG incorporated into the
      polymer backbone, and any unreacted units removed. Optimum formulation alpha-CH
      CHF/PLF68, 1% produced the highest bioactivity, enzyme encapsulation (20.08+/
      3.91%), loading (22.31+/-4.34 MUg/mg), FPF (fine particle fraction) (37.63+/
      0.97%); FPD (fine particle dose) (179.88+/-9.43 MUg), MMAD (mass median
      aerodynamic diameter) (2.95+/-1.61 MUm), and the mucinolytic activity was equal
      to the native non-encapsulated enzyme up to 5h. DNase I-CHF/PLF68, 1% resulted in
      enzyme encapsulation (17.44+/-3.11%), loading (19.31+/-3.27 MUg/mg) and activity
      (81.9+/-2.7%). The results indicate PEG-co-(PGA-co-PDL) can be considered as a
      potential biodegradable polymer carrier for dry powder inhalation of
      macromolecules for treatment of local pulmonary diseases.

PMID- 23124107
TI  - Aqueous solubility: simple predictive methods (in silico, in vitro and bio
      relevant approaches).
AB  - Aqueous solubility is a key physicochemical attribute required for the
      characterisation of an active pharmaceutical ingredient (API) during drug
      discovery and beyond. Furthermore, aqueous solubility is highly important for
      formulation selection and subsequent development processes. This review provides
      a summary of simple predictive methods used to assess aqueous solubility as well
      as an assessment of the more complex in silico methodologies and a review of the
      recent solubility challenge. In addition, a summary of experimental methods to
      determine solubility is included, with a discussion of some potential pitfalls. 

PMID- 23124108
TI  - Detoxifying emulsion for overdosed aspirin intoxication.
AB  - Aspirin overdose could lead to intoxication, with the clinical manifestations of
      vomit, pulmonary edema and severe dyspnea. Stomach washing, emetics and activated
      charcoal are the common treatments with a limited efficiency for the
      intoxication. In this study, an active emulsion for aspirin intoxication was
      prepared with the detoxifying efficiency of 100% in less than 15 min, with the
      conditions of dodecane used as the oil phase, 8% Abil EM90 as the surfactant and
      0.1 mol/L sodium hydroxide as the inner aqueous phase in a volume ratio of 2
      between internal aqueous phase and the oil phase.

PMID- 23124109
TI  - Crucial role of the N-glycans on the viral E-envelope glycoprotein in DC-SIGN
      mediated dengue virus infection.
AB  - We generated in the mosquito cell line C6/36 a dengue virus (DENV) resistant to
      Hippeastrum hybrid agglutinin (HHA), a carbohydrate-binding agent (CBA). The
      genotype and phenotype were characterized of the HHA resistant (HHA(res)) DENV
      compared to the wild-type (WT) DENV. Sequencing the structural proteins of
      HHA(res) resulted in two mutations, N67D and T155I, indicating a deletion of both
      N-glycosylation sites on the viral envelope E-glycoprotein. The HHA(res) DENV
      could replicate in mammalian and mosquito cells that are lacking dendritic cell
      specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN)
      expression. In contrast, DC-SIGN expressing human cells namely monocyte-derived
      dendritic cells as well as DC-SIGN-transfected cells were no longer susceptible
      to HHA(res) DENV. This demonstrates a crucial role of the N-glycans in the E
      glycoprotein in the infection of dendritic cells, which constitute primary target
      cells of DENV during viral pathogenesis in the human body.

PMID- 23124111
TI  - A Ni@ZrO2 nanocomposite for ethanol steam reforming: enhanced stability via
      strong metal-oxide interaction.
AB  - This communication describes the synthesis of a nanocomposite Ni@ZrO2 catalyst
      with enhanced metal-support interaction by introducing metal nanoparticles into
      the framework of the oxide support. The catalyst shows high catalytic activity
      and stability for hydrogen production via steam reforming of ethanol.

PMID- 23124110
TI  - Long distance relationships: enhancer-promoter communication and dynamic gene
      transcription.
AB  - The three-dimensional regulation of gene transcription involves loop formation
      between enhancer and promoter elements, controlling spatiotemporal gene
      expression in multicellular organisms. Enhancers are usually located in non
      coding DNA and can activate gene transcription by recruiting transcription
      factors, chromatin remodeling factors and RNA Polymerase II. Research over the
      last few years has revealed that enhancers have tell-tale characteristics that
      facilitate their detection by several approaches, although the hallmarks of
      enhancers are not always uniform. Enhancers likely play an important role in the
      activation of genes by functioning as a primary point of contact for
      transcriptional activators, and by making physical contact with gene promoters
      often by means of a chromatin loop. Although numerous transcriptional regulators
      participate in the formation of chromatin loops that bring enhancers into
      proximity with promoters, the mechanism(s) of enhancer-promoter connectivity
      remain enigmatic. Here we discuss enhancer function, review some of the many
      proteins shown to be involved in establishing enhancer-promoter loops, and
      describe the dynamics of enhancer-promoter contacts during development,
      differentiation and in specific cell types.

PMID- 23124112
TI  - UCP2 inhibition triggers ROS-dependent nuclear translocation of GAPDH and
      autophagic cell death in pancreatic adenocarcinoma cells.
AB  - Mitochondrial uncoupling protein 2 (UCP2) can moderate oxidative stress by
      favoring the influx of protons into the mitochondrial matrix, thus reducing
      electron leakage from respiratory chain and mitochondrial superoxide production.
      Here, we demonstrate that UCP2 inhibition by genipin or UCP2 siRNA strongly
      increases reactive oxygen species (ROS) production inhibiting pancreatic
      adenocarcinoma cell growth. We also show that UCP2 inhibition triggers ROS
      dependent nuclear translocation of the glycolytic enzyme glyceraldehyde 3
      phosphate dehydrogenase (GAPDH), formation of autophagosomes, and the expression
      of the autophagy marker LC3-II. Consistently, UCP2 over-expression significantly
      reduces basal autophagy confirming the anti-autophagic role of UCP2. Furthermore,
      we demonstrate that autophagy induced by UCP2 inhibition determines a ROS
      dependent cell death, as indicated by the apoptosis decrease in the presence of
      the autophagy inhibitors chloroquine (CQ) or 3-methyladenine (3-MA), or the
      radical scavenger NAC. Intriguingly, the autophagy induced by genipin is able to
      potentiate the autophagic cell death triggered by gemcitabine, the standard
      chemotherapeutic drug for pancreatic adenocarcinoma, supporting the development
      of an anti-cancer therapy based on UCP2 inhibition associated to standard
      chemotherapy. Our results demonstrate for the first time that UCP2 plays a role
      in autophagy regulation bringing new insights into mitochondrial uncoupling
      protein field.

PMID- 23124114
TI  - In situ fabrication of ultrathin porous alumina and its application for
      nanopatterning Au nanocrystals on the surface of ion-sensitive field-effect
      transistors.
AB  - In situ fabrication in a single step of thin films of alumina exhibiting a
      thickness of less than 100 nm and nanopores with a highly regular diameter
      distribution in order to pattern nanostructures over field-effect devices is a
      critical issue and has not previously been demonstrated. Here we report the
      fabrication in situ of 50 nm thick ultrathin nanoporous alumina membranes with a
      regular pore size directly over metal-free gate ion-sensitive field-effect
      transistors. Depositing thin films of aluminum by an electron beam at a
      relatively low rate of deposition on top of chips containing the transistors and
      using a conventional single-step anodization process permits the production of a
      well-adhering nanoporous ultrathin layer of alumina on the surface of the
      devices. The anodization process does not substantially affect the electrical
      properties of the transistors. The small thickness and pore size of ultrathin
      alumina membranes allow them to be sequentially employed as masks for patterning
      Au nanocrystals grown by an electroless approach directly on the top of the
      transistors. The patterning process using a wet chemical approach enables the
      size of the patterned crystals to be controlled not only by the dimensions of the
      pores of alumina, but also by the concentration of the reactants employed.
      Surface modification of these nanocrystals with alkanethiol molecules
      demonstrates that the electrostatic charge of the functional groups of the
      molecules can modulate the electrical characteristics of the transistors. These
      results represent substantial progress towards the development of novel
      nanostructured arrays on top of field-effect devices that can be applied for
      chemical sensing or non-volatile memories.

PMID- 23124113
TI  - Capturing single L-type Ca(2+) channel function with optics.
AB  - Advances in imaging technology have allowed optical analysis of Ca(2+)-permeable
      ion channel activity. Here, we briefly review novel developments in optical
      recording of L-type voltage-dependent Ca(2+) channel (LTCC) function with high
      spatial and temporal resolution. Underlying principles supporting the use of
      total internal reflection fluorescence (TIRF) microscopy for optical measurement
      of channel activity and new functional characteristics of LTCCs revealed by
      application of this approach are discussed. Visualization of Ca(2+) influx
      through single LTCCs ("LTCC sparklets") has demonstrated that channel activity is
      regionally heterogeneous and that clustered channels are capable of operating in
      a cooperative, or "coupled" manner. In light of these findings, we describe a
      current molecular model for the local control of LTCC activity and coupled gating
      in physiological and pathological contexts. This article is part of a Special
      Issue entitled: 12th European Symposium on Calcium.

PMID- 23124116
TI  - Swarming motility in Bradyrhizobium japonicum.
AB  - Flagellar-driven bacterial motility is an important trait for colonization of
      natural environments. Bradyrhizobium japonicum is a soil species that possesses
      two different flagellar systems: one subpolar and the other lateral, each with a
      filament formed by a different set of flagellins. While synthesis of subpolar
      flagellins is constitutive, translation of lateral flagellins was detected in
      rhizobia grown with l-arabinose, but not with d-mannitol as sole carbon source,
      independently of whether bacteria were in liquid or semisolid medium. We
      characterized swarming of B. japonicum in semisolid medium and found that this
      motility was faster with l-arabinose than with d-mannitol. By using mutants with
      deletions in each flagellin set, we evaluated the contribution of each flagellum
      system to swarming in semisolid culture media, and in soil. Mutants devoid of
      either of the flagella were affected in swarming in culture media, with this
      impairment being stronger for mutants without lateral flagella. In sterile soil
      at 100% or 80% field capacity, flagellar-driven motility of mutants able to swim
      but impaired in swarming was similar to wild type, indicating that swimming was
      the predominant movement here.

PMID- 23124117
TI  - Getting in touch: microbial molecular devices for cell-cell and cell-surface
      interactions.

PMID- 23124115
TI  - Biomolecular mechanism of urinary stone formation involving osteopontin.
AB  - Urinary stones consist of two phases-an inorganic (mineral) phase and an organic
      (matrix) phase. Studies on the organic components of kidney stones have been
      undertaken later than those on the inorganic components. After osteopontin was
      identified as one of the matrix components, the biomolecular mechanism of urinary
      stone formation became clearer. It also triggered the development of new
      preventive treatments. Osteopontin expression is sporadically observed in normal
      distal tubular cells and is markedly increased in stone-forming kidneys. Calcium
      oxalate crystals adhering to renal tubular cells are incorporated into cells by
      the involvement of osteopontin. Stimulation of crystal-cell adhesion impairs the
      opening of mitochondrial permeability transition pores (mPTP) in tubular cells
      and produces oxidative stress, apoptosis, and osteopontin expression. Macrophages
      phagocytose and digest a small amount of crystals, but many crystals aggregate
      into a mass containing osteopontin and epithelial cell debris and are excreted
      into the renal tubular lumen, becoming nuclei of urinary stones. This
      biomolecular mechanism is similar to atherosclerotic calcification. Based on
      these findings, new preventive treatments have been developed. Dietary control
      such as low-cholesterol intake and the ingestion of antioxidative foods and
      vegetables have successfully reduced the 5-year recurrence rate. Osteopontin
      antibodies and cyclosporine A, which blocks the opening of mPTP, have markedly
      inhibited the expression of osteopontin and urinary stone formation in animal
      models.

PMID- 23124118
TI  - High expression of survivin is prognostic of shorter survival but not predictive
      of adjuvant gemcitabine benefit in patients with resected pancreatic
      adenocarcinoma.
AB  - Overexpression of survivin has been associated with gemcitabine resistance in
      pancreatic adenocarcinoma, but previous studies have shown conflicting results.
      This study aims to determine its prognostic value in resected pancreatic
      adenocarcinoma with or without adjuvant therapy and its predictive value in
      adjuvant gemcitabine benefit in patients with resected pancreatic adenocarcinoma.
      This study included 118 patients who underwent pancreaticoduodectomy from 1999 to
      2007, with no neoadjuvant chemoradiation. Forty-five patients received adjuvant
      gemcitabine. Survivin expression was assessed immunohistochemically and was
      graded as low (<=10% positive cells) and high (>10% positive cells) by recursive
      partitioning analysis. Prognostic factors, including tumor size, number of
      positive lymph nodes, perineural invasion, and stage, were identified for overall
      survival (OS) and progression-free survival (PFS) using Cox proportional hazards
      models. Multivariable analysis of the entire cohort revealed that both high
      survivin expression and perineural invasion predict significantly shorter OS
      (hazard ratio [HR] 2.0, p=0.01; HR 1.9, p=0.01, respectively) and shorter PFS (HR
      1.9, p=0.04; HR 3.1, p=0.0006, respectively). Expression of survivin predicts
      neither OS nor PFS in patients treated with adjuvant gemcitabine. In summary,
      high expression of survivin is associated with shorter OS and PFS in patients
      with resected pancreatic adenocarcinoma after adjusting for other
      histopathological factors. However, survivin has no predictive value of adjuvant
      gemcitabine benefit.

PMID- 23124121
TI  - Learning is fundamental.

PMID- 23124120
TI  - An amplified chemiluminescence aptasensor based on bi-resonance energy transfer
      on gold nanoparticles and exonuclease III-catalyzed target recycling.
AB  - We have developed an amplified chemiluminescence aptasensor based on bi-resonance
      energy transfer on gold nanoparticles and exonuclease III-catalyzed target
      recycling. This assay exhibits high detection sensitivity over traditional
      biosensors in three orders of magnitude and high specificity for target
      molecules.

PMID- 23124122
TI  - Placing rehabilitation and recovery after spinal cord injury into a biographical
      context: a U.S. versus Danish case comparison.
AB  - Although medical and technological advances have extended survival rates through
      ever more effective acute clinical management for people with spinal cord
      injuries, the links between rehabilitation and recovery are less well understood.
      With ever shorter length of stays in inpatient rehabilitation, the focus of
      support has been shifting toward outpatient support pathways. In this article,
      the narrated rehabilitation experiences of two young men with comparable spinal
      cord injuries in the United States and Denmark are contrasted. From their
      biographical narratives, we examine the sociocontextual factors that underpin the
      rehabilitation pathways in two quite distinctive social and healthcare
      environments. Our analysis raises questions about the importance of factors such
      as readiness, timeliness, duration, and appropriateness of rehabilitation to
      facilitate independent living, achieve meaningful recovery, and provide equitable
      access to the goods and services afforded by society.

PMID- 23124124
TI  - A qualitative study of nutritional behaviors in adults with multiple sclerosis.
AB  - Few studies have explored how people living with multiple sclerosis (MS) cope
      with impairments and disability to participate in nutritional behaviors, such as
      meal preparation and grocery shopping. Thus, we conducted a qualitative study
      among eight individuals with MS who experienced mobility impairments. The eight
      individuals participated in semistructured, face-to-face interviews that focused
      on obtaining narratives about day-to-day dietary habits, preparing food, grocery
      shopping, and going to restaurants. Interviews were analyzed using an inductive
      category and theme development approach. Overall themes were (a) "it's a lot of
      work," (b) "it's not just up to me," (c) sifting through nutritional information,
      and (d) "why I eat what I eat." Participants frequently reported fatigue and
      mobility impairments as barriers to engagement in nutritional behaviors and often
      described family members as the "gatekeepers" for food selection and preparation
      (i.e., providing tangible support). Future research should explore the
      effectiveness of nutritional interventions that target family dynamics and create
      a supportive social environment to promote healthy eating habits and nutritional
      autonomy.

PMID- 23124123
TI  - The relationship between perceived life changes and depression in caregivers of
      stroke patients.
AB  - Most people with stroke are being cared for at home by family caregivers. Giving
      care is stressful, and family caregivers are predisposed to care-related
      complications such as life changes and depression. This article is a report of a
      study that examined the relationship between the perceived care-related life
      changes and depression in family caregivers of people with stroke, and it
      identified predictors influencing depression and perceived care-related life
      changes. A convenience sample of 60 family caregivers completed one demographic
      data sheet and two questionnaires: Bakas Caregiving Outcomes Scale and Center for
      Epidemiologic Studies Depression Scale. Data were collected in a 1-month period
      in 2008. According to the findings, the mean score of the subjects on the Bakas
      Caregiving Outcomes Scale was -5.70, representing an overall negative change
      related to the caregiving role. The prevalence of people at a risk of depression
      or being depressed was 40%. Correlation analysis showed that, as perceived life
      changes score decreases (change for the worst), the score for the feeling of
      depression increases (r = -.692, p <= .001). Stroke survivors' functional
      disability significantly predicted both perceived care-related life changes and
      depression in caregivers. Assessment of caregivers of people with stroke for
      depressive symptoms should be incorporated in the initial nursing assessment
      process. The perceived life changes among caregivers should be closely monitored,
      and follow-up meetings should be planned to support caregivers. The functional
      disability in people with stroke could be a valuable criterion for planning care
      for their caregivers.

PMID- 23124125
TI  - The use of focus groups to characterize symptoms in persons with multiple
      sclerosis.
AB  - Multiple sclerosis is a chronic neurological disease with a myriad of symptoms.
      Because most work has been quantitative, it is important to capture symptoms as
      described by patients who experience them, using a qualitative approach. The
      purpose of our study was to describe and identify symptoms, with emphasis on co
      occurrence, using focus groups. Three focus groups were conducted (N = 16) with
      relapsing-remitting multiple sclerosis patients. Common symptoms, described as
      both singular and co-occurring, were problems with balance, cognition, vision,
      and heat intolerance. These findings augment past characterizations of symptoms
      experienced in persons with relapsing-remitting multiple sclerosis and provide
      evidence for future studies.

PMID- 23124126
TI  - The effects of open and closed endotracheal suctioning on intracranial pressure
      and cerebral perfusion pressure: a crossover, single-blind clinical trial.
AB  - Although endotracheal suctioning is a routine nursing intervention, this
      procedure can lead to an increase in intracranial pressure (ICP). This study was
      planned to determine the appropriate suctioning technique (open system suctioning
      [OS] and closed system suctioning [CS]) to minimize variability of ICP and
      cerebral perfusion pressure (CPP) in neurologically impaired patients. The study,
      which was designed as a crossover, single-blind clinical trial, consisted of 32
      neurosurgical patients who underwent ICP monitoring, intra-arterial blood
      pressure monitoring, and endotracheal intubation in the intensive care unit.
      According to the need for suctioning, each patient in the experimental and
      control groups underwent suctioning with both closed and open systems. Recordings
      were composed of the patients' ICP, mean arterial blood pressure, CPP, heart rate
      (HR), and arterial blood gases during suctioning. It was observed that both
      suctioning techniques significantly increased ICP, mean arterial blood pressure,
      CPP, and HR; ICP was found to be significantly higher in OS compared with CS,
      whereas there were no significant differences in CPP and HR between the two
      techniques. The patients suctioned using OS had significantly lower mean PaO(2)
      than those suctioned using CS; however, the comparison of the two techniques
      revealed no significant differences in PaCO(2). The data obtained indicate that
      CS, compared with OS, can be used safely on this patient group.

PMID- 23124128
TI  - Proteomic analysis of TNF-alpha-activated endothelial cells and endothelial
      microparticles.
AB  - Endothelial microparticles (EMPs) are small vesicles released from endothelial
      cells (ECs) and found circulating in the blood. EMPs are formed by a plasma
      membrane surrounding a small amount of cytosol and contain a subset of cellular
      proteins. As the number of EMPs in the blood increases with certain diseases,
      they may be an attractive biomarker for clinical diagnosis. Proteomic analysis of
      EMPs has been previously performed by mass spectrometry. However, the proteomic
      information of the ECs that secrete EMPs is lacking. This study introduces an in
      vitro model of activated ECs we created for proteomic analyses and reports the
      changes of the protein content in the ECs and EMPs using proteomic methods. Thus,
      this study provides valuable information for the analysis of the highly dynamic
      secretion process of EMPs. There is a direct correlation between the proteins
      that form EMPs and tumor necrosis factor-alpha (TNF-alpha)-activated ECs. The
      endothelial proteins transferred by EMPs may play important roles in the
      interaction between EMPs and the target cells, which may lead to endothelial
      dysfunction. 

PMID- 23124129
TI  - Detergent enzymatic treatment for the development of a natural acellular matrix
      for oesophageal regeneration.
AB  - PURPOSE: Tissue engineering of the oesophagus has been proposed as a therapeutic
      alternative to organ transplantation. We previously demonstrated that a detergent
      enzymatic treatment (DET) is a valid method to obtain an acellular matrix with
      preservation of the native architecture. In this study, we aimed to develop a
      natural acellular matrix from pig oesophagus, as a valid framework for
      oesophageal replacement. METHODS: Pig oesophagi (n = 4) were decellularized with
      continuous luminal infusion of DET. To evaluate the efficiency of the
      decellularization, samples were assessed by histology and DNA quantification.
      Moreover, the ultra-structural characteristics of the acellular matrix were
      investigated by scanning electron microscopy (SEM) and transmission electron
      microscopy (TEM). RESULTS: Decellularization of the oesophagus was achieved after
      three cycles of DET. Histological analysis showed the maintenance of tissue
      matrix architecture with absence of cellular elements, verified by measurement of
      DNA. SEM and TEM analysis confirmed preservation of the ultra-structural
      characteristics of the native tissue. CONCLUSIONS: Oesophageal acellular matrix
      can be successfully obtained by decellularization of pig oesophagus using a
      gentle DET via the oesophageal lumen. This decellularization method preserves the
      ultrastructure of the native tissue and could represent the basis for a tissue
      engineered oesophagus.

PMID- 23124130
TI  - ROCK inhibitor (Y-27632) disrupts somitogenesis in chick embryos.
AB  - AIM: In chick embryos, administration of cadmium (Cd) induces ventral body wall
      defects (VBWD) similar to human omphalocele. It has been shown that failure of
      proper VBW formation may be due to disruption of somite development during early
      embryogenesis. In the VBWD chick model, Cd causes abnormal cell death in the
      somitic region resulting in improperly developed somites and tortuosity of the
      neural tube. However, the exact molecular mechanisms leading to VBWD still remain
      unclear. Wnt signaling is crucial during embryogenesis and plays a key role in
      normal somite formation. The Rho-associated coiled-coil containing protein kinase
      (ROCK) is involved in the non-canonical Wnt pathway which controls actin
      cytoskeleton assembly and cell contractility, and contributes to several
      developmental processes including somitogenesis. ROCK gene expression levels have
      recently been reported to be significantly decreased in the Cd-induced VBWD chick
      model. We designed this study to investigate the hypothesis that administration
      of ROCK inhibitor (Y-27632) in the absence of Cd disrupts somitogenesis and could
      contribute to the development of VBWD during early embryogenesis. METHODS: After
      60 h of incubation chick embryos were transferred from eggs to culture dishes
      containing 20 MUM of Y-27632 for experimental group (Y-27, n = 22) or chick
      saline for controls (n = 14). Following 24 h in the incubator they were assessed
      for stage development and gross abnormalities in morphology using the dissecting
      microscope. Western blot was performed to confirm Y-27632 inhibition of ROCK
      downstream signaling using an antibody against phosphorylated cofilin-2. RESULTS:
      20 (90.9 %) embryos from Y-27 group and all controls were alive at examination.
      Morphological abnormalities were detected in 14 (70 %) Y-27 embryos. Somites
      appeared improperly developed, flattened in the cranio-caudal direction, and
      elongated in transverse direction in relation to controls. Chick embryos in Y-27
      also presented with tortuosity of the neural tube in the lumbosacral region.
      Western blot analysis showed inhibition of cofilin-2 phosphorylation in affected
      embryos in comparison to controls. CONCLUSION: Our study provides evidence that
      ROCK inhibitor results in the disruption of normal somitogenesis in chick embryos
      which may contribute to the failure of fusion of the anterior abdominal wall
      causing VBWD.

PMID- 23124131
TI  - In vitro CO2-induced ROS production impairs cell cycle in SH-SY5Y neuroblastoma
      cells.
AB  - PURPOSE: We evaluated in vitro the role of CO(2)-induced oxidative stress on the
      expression of proteins involved in cell-cycle regulation of neuroblastoma cells.
      METHODS: SH-SY5Y cells were exposed to CO(2) at 15 mmHg pressure (100 %) for 4 h
      and then moved to normal condition for 24 h. Control cells were maintained in 5 %
      CO(2) for the same time. ROS production was determined by fluorescent staining
      with H2DCF-DA. DNA damage was measured by COMET assay. p53 protein expression was
      analyzed by western blot and confocal laser scanning microscopy was used to
      evaluate its sub-cellular localization. Cyclin expression was quantified by real
      time PCR and western blot. Cell-cycle analysis was performed by FACS. RESULTS:
      CO(2) incubation was associated with an increase in ROS production (p < 0.01),
      cell DNA damage mainly after 24 h (12 % increase of tail DNA content and 4-fold
      increase of tail length) and a significant up-regulation in p53 expression at 24
      h with an intense nuclear staining. In CO(2)-treated cells, we observed an S
      phase arrest in correlation with a reduction of cyclin B1 expression.
      CONCLUSIONS: In vitro-simulated pneumoperitoneum environment with CO(2) induces
      oxidative stress and cell DNA damage, leading to p53 up-regulation involved in
      cell-cycle arrest of neuroblastoma cells.

PMID- 23124132
TI  - When is virtual reality "therapy"?
AB  - The use of virtual reality (VR) systems within physical rehabilitation clinical
      practice and research is rapidly developing, highlighting the need for consensus
      as to the meaning and relevance of the label "VR therapy." The purpose of this
      communication is to argue that explicit examination of the inferences underlying
      this label and discussion regarding the role of clinicians in VR implementation
      are required. In this vein, we propose what we consider to be a more relevant
      label and discuss the need for evidence to support knowledge translation
      initiatives for therapists interested in integrating VR systems within clinical
      practice.

PMID- 23124133
TI  - Does postacute care site matter? A longitudinal study assessing functional
      recovery after a stroke.
AB  - OBJECTIVE: To determine the impact of postacute care site on stroke outcomes.
      DESIGN: Prospective cohort study. SETTING: Four northern California hospitals
      that are part of a single health maintenance organization. PARTICIPANTS: Patients
      with stroke (N=222) enrolled between February 2008 and July 2010. INTERVENTION:
      Not applicable. MAIN OUTCOME MEASURE: Baseline and 6-month assessments were
      performed using the Activity Measure for Post Acute Care (AM-PAC), a test of self
      reported function in 3 domains: Basic Mobility, Daily Activities, and Applied
      Cognition. RESULTS: Of the 222 patients analyzed, 36% went home with no
      treatment, 22% received home health/outpatient care, 30% included an inpatient
      rehabilitation facility (IRF) in their care trajectory, and 13% included a
      skilled nursing facility (but not IRF) in their care trajectory. At 6 months,
      after controlling for important variables such as age, functional status at acute
      care discharge, and total hours of rehabilitation, patients who went to an IRF
      had functional scores that were at least 8 points higher (twice the minimally
      detectable change for the AM-PAC) than those who went to a skilled nursing
      facility in all 3 domains and in 2 of 3 functional domains compared with those
      who received home health/outpatient care. CONCLUSIONS: Patients with stroke may
      make more functional gains if their postacute care includes an IRF. This finding
      may have important implications as postacute care delivery is reshaped through
      health care reform.

PMID- 23124134
TI  - Climate change and food security: health impacts in developed countries.
AB  - BACKGROUND: Anthropogenic climate change will affect global food production, with
      uncertain consequences for human health in developed countries. OBJECTIVES: We
      investigated the potential impact of climate change on food security (nutrition
      and food safety) and the implications for human health in developed countries.
      METHODS: Expert input and structured literature searches were conducted and
      synthesized to produce overall assessments of the likely impacts of climate
      change on global food production and recommendations for future research and
      policy changes. RESULTS: Increasing food prices may lower the nutritional quality
      of dietary intakes, exacerbate obesity, and amplify health inequalities. Altered
      conditions for food production may result in emerging pathogens, new crop and
      livestock species, and altered use of pesticides and veterinary medicines, and
      affect the main transfer mechanisms through which contaminants move from the
      environment into food. All these have implications for food safety and the
      nutritional content of food. Climate change mitigation may increase consumption
      of foods whose production reduces greenhouse gas emissions. Impacts may include
      reduced red meat consumption (with positive effects on saturated fat, but
      negative impacts on zinc and iron intake) and reduced winter fruit and vegetable
      consumption. Developed countries have complex structures in place that may be
      used to adapt to the food safety consequences of climate change, although their
      effectiveness will vary between countries, and the ability to respond to
      nutritional challenges is less certain. CONCLUSIONS: Climate change will have
      notable impacts upon nutrition and food safety in developed countries, but
      further research is necessary to accurately quantify these impacts. Uncertainty
      about future impacts, coupled with evidence that climate change may lead to more
      variable food quality, emphasizes the need to maintain and strengthen existing
      structures and policies to regulate food production, monitor food quality and
      safety, and respond to nutritional and safety issues that arise.

PMID- 23124135
TI  - BDE-99 congener induces cell death by apoptosis of human hepatoblastoma cell line
      - HepG2.
AB  - Polybrominated Diphenyl Ethers (PBDEs) are an important class of flame retardants
      with a wide range of toxic effects on biotic and abiotic systems. The toxic
      mechanisms of PBDEs are still not completely understood because there are several
      different congeners with different chemical and biological characteristics. BDE
      99 is one of these, widely found in the environment and biological samples,
      showing evidence of neurotoxic and endocrine disruption activities, but with
      little information about its action mechanism described in the current
      literature. This work investigated the effects of BDE-99 on the HepG2 cell line
      in order to clarify its toxic mechanism, using concentrations of 0.5-25 MUM (24
      and 48 h). Our results showed that BDE-99 could cause cell death in the higher
      concentrations, its activity being related to a decrease in mitochondrial
      membrane potential and an accumulation of ROS. It was also shown that BDE-99
      induced the exposure of phosphatidylserine, caspases 3 and 9 activation and DNA
      fragmentation in HepG2 cells, without causing the release of LDH. Thus it was
      shown that BDE-99 could cause HepG2 cell death by apoptosis, suggesting its
      toxicity to the human liver.

PMID- 23124136
TI  - Growth hormone reverses streptozotocin-induced cognitive impairments in male
      mice.
AB  - In recent decades, growth hormone (GH) replacement therapy in human subjects
      deficient in the hormone has resulted in a number of beneficial effects on
      cognitive performance. Studies in hypophysectomised rats report similar effects
      of GH treatment on learning and memory tasks. The purpose of this study was to
      investigate the ability of GH to reverse learning impairments in mice with
      streptozotocin (STZ)-induced diabetes. Diabetic and control mice were given
      recombinant human GH (rhGH) 0.1 IU/kg/day for ten consecutive days. In the latter
      phase of the treatment the cognitive abilities of the mice were tested using the
      Barnes maze (BM). A profound hormonal effect was seen when analysing the search
      patterns used by the animals in the maze. rhGH treatment significantly
      counteracted the cognitive disabilities expressed as lack of direct search
      strategies on the last day in the BM. In addition, the number of primary errors
      made by diabetic mice during the acquisition phase was reduced by rhGH treatment,
      although the primary escape latency was unchanged in these animals when compared
      to saline-treated diabetic animals. These results suggest that specific cognitive
      impairments induced by STZ, i.e. the disabilities seen in strategic behaviour,
      could be reversed by exogenous hormone treatment. Our findings highlight the
      influence of GH on brain function and in particular on cognitive behaviour
      related to learning and memory.

PMID- 23124137
TI  - Fusiform gyrus responses to neutral and emotional faces in children with autism
      spectrum disorders: a high density ERP study.
AB  - Face processing is a neural mechanism that allows understanding social
      information and cues conveyed by faces, whose dysfunction has been postulated to
      underlie some of the behavioral impairments characterizing autism spectrum
      disorders (ASD). A special region of the cortex, the fusiform gyrus (FG), is
      believed to be the specific area for processing face features and emotions.
      However, behavioral, fMRI and ERP studies addressed to investigate the role of FG
      dysfunction in ASD have led to conflicting results. Using a high-density EEG
      system, we recorded the face-sensitive ERP to neutral and emotional (happiness
      and fearful) faces, as a measure of early activity of the FG, in children with
      high functioning ASD. By controlling a number of experimental and clinical
      variables that could have biased previous research--such as gaze direction,
      attention to tasks, stimulus appearance and clinical profiles--we aimed to assess
      the effective role of the FG in the face emotion processing deficit hypothesized
      in ASD. No significant differences in early face-sensitive ERP components were
      found between ASD and neurotypical children. However, a systematic latency delay
      and amplitude reduction of all early potentials were observed in the ASD group,
      regardless of the stimulus, although more evident for emotions. Therefore, we can
      assume a diffuse dysfunction of neural mechanisms and networks in driving and
      integrating social information conveyed by faces, in particular when emotions are
      involved, rather than a specific impairment of the FG-related face processing
      circuit. Nevertheless, there is need of further investigation.

PMID- 23124138
TI  - The tyrosine phosphatase TC48 interacts with and inactivates the oncogenic fusion
      protein BCR-Abl but not cellular Abl.
AB  - The chimeric oncoprotein BCR-Abl exhibits deregulated protein tyrosine kinase
      activity and is responsible for the pathogenesis of certain human leukemias, such
      as chronic myelogenous leukemia. The activities of cellular Abl (c-Abl) and BCR
      Abl are stringently regulated and the cellular mechanisms involved in their
      inactivation are poorly understood. Protein tyrosine phosphatases can negatively
      regulate Abl mediated signaling by dephosphorylating the kinase and/or its
      substrates. This study investigated the ability of the intracellular T cell
      protein tyrosine phosphatase (TCPTP/PTPN2) to dephosphorylate and regulate the
      functions of BCR-Abl and c-Abl. TCPTP is expressed as two alternately spliced
      isoforms - TC48 and TC45, which differ in their C-termini and localize to the
      cytoplasm and nucleus respectively. We show that TC48 dephosphorylates BCR-Abl
      but not c-Abl and inhibits its activity towards its substrate, CrkII. Y1127 and
      Y1294 residues whose phosphorylation corresponds with BCR-Abl activation status
      were the primary sites targeted by TC48. Co-localization and immunoprecipitation
      experiments showed that TC48 interacted with BCR-Abl but not with c-Abl, and BCR
      domain was sufficient for interaction. TC48 expression resulted in the
      stabilization of Bcr-Abl protein dependent on its phosphatase activity.
      Inactivation of cellular TC48 in K562 cells by stable expression of a dominant
      negative catalytically inactive mutant TC48, enhanced proliferation. TC48
      expressing K562 clones showed reduced proliferation and enhanced sensitivity to
      STI571 compared to control clones suggesting that TC48 can repress the growth of
      CML cells. This study identifies a novel cellular regulator that specifically
      inhibits the activity of oncogenic BCR-Abl but not that of the cellular Abl
      kinase.

PMID- 23124139
TI  - Timing of chemotherapy-induced neutropenia is a prognostic factor in patients
      with metastatic non-small-cell lung cancer: a retrospective analysis in
      gemcitabine-plus-platinum-treated patients.
AB  - PURPOSE: Chemotherapy-induced neutropenia (CIN) has been associated with better
      therapeutic results in studies of various tumors. Herein, we explored the
      relationship between timing (onset) of CIN and clinical outcomes of patients with
      metastatic non-small-cell lung cancer (NSCLC). METHODS: Patients with stage IV
      NSCLC receiving at least two cycles of first-line doublet chemotherapy
      (gemcitabine plus platinum) were reviewed retrospectively. Subjects were
      stratified by onset of CIN into two groups: early-onset (lowest neutrophil count
      of cycles 1-2 <2.0 * 10(9)/L) and non-early-onset. The non-early-onset group was
      further subdivided into late-onset (lowest neutrophil count of cycles 3-6 <2.0 *
      10(9)/L) and absence of neutropenia. RESULTS: A total of 123 patients were
      studied. Significantly better disease control rate, progression-free survival
      (PFS), and overall survival (OS) were observed in early-onset versus non-early
      onset patients. Median PFS of 5.1 and 3.8 months (p = 0.0016) and median OS of
      16.7 and 11.2 months (p = 0.0004) were achieved for these groups, respectively.
      Patient subsets with late-onset and absence of neutropenia showed similarly poor
      clinical outcomes, with 4.8 and 3.8 months median PFS (p = 0.5067) and 13.0 and
      11.2 months median OS (p = 0.6304), respectively. CONCLUSIONS: Timing of CIN is
      predictive of prognosis in patients with metastatic NSCLC receiving
      gemcitabine/platinum doublet chemotherapy. Better clinical outcomes were achieved
      when onset of neutropenia was early versus late or absent altogether. Further
      research is warranted to determine whether above findings are applicable to other
      chemotherapeutic regimens.

PMID- 23124140
TI  - Brain metastases as the first symptom of lung cancer: a clinical study from an
      Asian medical center.
AB  - OBJECTIVE: Brain metastasis as the first symptom of lung cancer is a unique
      clinical entity. We conducted a retrospective study to investigate the clinical
      characteristics and survival of patients with lung cancer whose first symptom was
      brain metastases in an Asian population. METHODS: A retrospective study of 186
      such patients who had been admitted to one institution in China between January
      1, 2003 and December 30, 2008 was performed. The following data were collected
      and analyzed: manifesting signs and symptoms, imaging studies, extracerebral
      metastases, initial diagnosis, treatment, and patient survival. RESULTS: This
      sample population exhibited high rates of misdiagnosis upon initial presentation
      (46.8 %). Fifty-seven (30.6 %) patients presented with silent extracerebral
      metastases. Pathologies among this cohort varied, and adenocarcinomas were most
      commonly observed. Most patients received surgical resection, and some patients
      had additional whole-brain radiotherapy or stereotactic radiosurgery. The median
      survival time for the entire cohort was 15 months (95 % confidence interval, 12.9
      17.1 months). Survival rates for 1, 2, and 5 years were 58.2, 34.2, and 6.5 %,
      respectively. The median survival time was 15, 14, 19, and 7 months for the gross
      total resection, incomplete resection, surgery + whole-brain radiotherapy, and
      surgery + stereotactic radiosurgery groups, respectively. CONCLUSIONS: Brain
      metastasis as the first symptom of lung cancer is a distinct clinical entity.
      Although overall survival was poor, combined treatments based on surgery for
      selected patients were reasonable with the exception of a minority who
      experienced long-term survival.

PMID- 23124141
TI  - Temporal changes in echocardiographic findings in cardiac and non-cardiac
      sarcoidosis patients.
AB  - OBJECTIVE: Echocardiography is used for the detection of cardiac sarcoid
      involvement in patients with non-cardiac sarcoidosis. Little information is
      available regarding temporal changes in left ventricular ejection fraction (LVEF)
      and left ventricular end-diastolic dimension (LVDd) in non-cardiac sarcoidosis
      patients. METHODS AND RESULTS: Fifty-four sarcoidosis patients who received
      periodic follow-up with echocardiography at our institute were enrolled in this
      study. At the time of initial ultrasonography, 13 patients were diagnosed with
      cardiac sarcoid involvement. All of the remaining 41 patients with extra-cardiac
      sarcoidosis only had a LVEF of >50%. During the median follow-up period of 39
      months, two (4.9%) of the non-cardiac sarcoidosis patients were diagnosed with
      cardiac sarcoid involvement; one patient showed a progressive decline in the LVEF
      over a short period of time. It was also found that two of 41 non-cardiac
      sarcoidosis patients showed declines in the LVEF of >10% per year; however, they
      were not diagnosed with cardiac sarcoidosis during the follow-up period.
      CONCLUSION: Rapid deterioration of left ventricular function may increase the
      suspicion of sarcoid involvement of the heart in non-cardiac sarcoidosis
      patients; however, we must be aware that a certain subfraction of patients may
      not demonstrate significant abnormalities in LVEF or LVDd on periodic
      echocardiographic follow-up.

PMID- 23124142
TI  - A low fT3 level as a prognostic marker in patients with acute myocardial
      infarctions.
AB  - OBJECTIVE: To investigate the association between low free triiodothyronine (fT3)
      levels and the severity and prognosis of patients with acute myocardial
      infarction. METHODS: A total of 501 patients with acute myocardial infarctions
      were enrolled in our study. The circulating levels of thyroid hormones and
      clinical parameters were assayed. The patients were categorized into either the
      low fT3 group or the normal fT3 group according to the fT3 level on admission.
      All patients underwent a follow-up for 10+/-2 months for mortality from any cause
      and the occurrence of any adverse major cardiac events (MACE). RESULTS: There
      were 171 patients in the low fT3 group (fT3<3.5 pmol/L) and 330 patients in the
      normal fT3 group (>=3.5 pmol/L). During the follow-up period, 33 patients died
      (6.6%) and the overall survival rates were 86.0% and 97.3% in patients with a low
      fT3 level and a normal fT3 level, respectively. The rates of MACE were 66.7% and
      45.5% in the patients with and those without low fT3 levels, respectively. Using
      a multivariable Cox proportional hazards model, the fT3 level was found to be the
      most important predictor of cumulative death and MACE (hazard ratio [HR] for
      death: 0.142, p<0.001 and HR for major adverse cardiac events: 0.748, p=0.007). A
      Kaplan-Meier analysis revealed that those patients with low fT3 levels had higher
      rates of MACE and death. CONCLUSION: A low fT3 level, a common phenomenon in
      patients with acute myocardial infarctions, is a strong predictor of short-term
      and long-term poor prognoses in patients with acute myocardial infarctions.

PMID- 23124143
TI  - Prevalence of angiographically defined obstructive coronary artery disease in
      asymptomatic patients with type 2 diabetes according to the coronary calcium
      score.
AB  - OBJECTIVE: The aim of this study was to determine whether the absence of coronary
      artery calcium (CAC) can safely exclude obstructive coronary artery disease (CAD)
      in asymptomatic patients with type 2 diabetes. METHODS: We enrolled 478
      consecutive asymptomatic patients with type 2 diabetes who visited the diabetes
      clinic of the Asan Medical Center between October 1, 2009 and December 31, 2010.
      All patients underwent 64-slice dual-source computed tomography (DSCT) for CAC
      scoring as well as computed tomography angiography (CTA). Patients with at least
      one significant coronary stenosis with >50% luminal narrowing were classified as
      having obstructive CAD. The findings were confirmed using conventional coronary
      angiography (CAG). RESULTS: Among the 478 patients, 157 (33%) had a CAC score of
      0 (CAC=0). Of these, 17 (11%) had obstructive CAD confirmed on CAG. The presence
      of CAC had a negative predictive value for obstructive CAD on CAG of 89% and a
      sensitivity of 88%, a specificity of 42% and a positive predictive value of 38%.
      A multivariate logistic regression analysis showed that current smoking habits
      were significantly associated with the presence of obstructive CAD in patients
      with CAC=0 after adjusting for traditional cardiovascular risk factors (odds
      ratio 4.87, 95% confidence interval 1.65-14.42, p=0.004). CONCLUSION: Our
      findings suggest that CAC=0 on 64-slice DSCT cannot safely exclude obstructive
      CAD on CAG in asymptomatic patients with type 2 diabetes, particularly in current
      smokers. CTA should be combined with CAC scoring in screening for CAD in
      asymptomatic patients with type 2 diabetes.

PMID- 23124144
TI  - Sarcomatous hepatocellular carcinoma with remittent fever.
AB  - We herein report a rare case of hepatocellular carcinoma (HCC) with sarcomatous
      changes. A 66-year-old man was admitted to our hospital with a high fever and
      upper abdominal pain. Initially, he was diagnosed as having a liver abscess;
      however, antibiotic treatment and drainage were ineffective. Further imaging
      studies revealed the typical appearance of HCC: the tumor had invaded the hepatic
      and portal veins. Surgical resection of the tumor was performed. A pathological
      examination demonstrated the presence of a sarcomatous hepatocellular carcinoma.
      Sarcomatous hepatocellular carcinoma with remittent fever is a rare disease
      entity.

PMID- 23124145
TI  - Pulmonary embolism caused by intimal sarcoma of the pulmonary artery.
AB  - We herein report the case of a 39-year-old woman with a pulmonary embolism caused
      by intimal sarcoma of the pulmonary artery. She presented with shortness of
      breath and leg edema. Computed tomography showed a low density area that extended
      from the main pulmonary artery to the bilateral pulmonary arteries. We diagnosed
      her to have a pulmonary thromboembolism. The thrombosis did not decrease after
      the administration of anti-coagulant therapy, and she underwent resection of the
      thrombotic tissue. Histopathologically, the surgical specimen was not found to be
      thrombotic tissue but rather an intimal sarcoma of the pulmonary artery. After
      undergoing surgery, she received radiation therapy and chemotherapy; however, she
      died 31 months after being diagnosed.

PMID- 23124146
TI  - Seizures and syncope due to complete atrioventricular block in a patient with
      acute myocarditis with a normal left ventricular systolic function.
AB  - A 43-year-old man was admitted to our hospital presenting with seizures and
      syncope. He had a history of a cold with a fever of 39 degrees C occurring three
      days earlier. Electrocardiography (ECG) showed complete atrioventricular block
      (AV block) with a maximum pause of 32 seconds, for which temporary pacing was
      performed. Echocardiography showed mild hypertrophy of the left ventricle (LV)
      with a normal ejection fraction of 61%. Coronary angiography showed normal
      coronary arteries. Then, an endomyocardial biopsy was performed, the results of
      which indicated a diagnosis of acute myocarditis. After admission, the complete
      atrioventricular block disappeared together with normalization of the LV wall
      thickness.

PMID- 23124147
TI  - Left main coronary artery thrombus resulting from combined protein C and S
      deficiency.
AB  - Inherited hypercoagulopathies such as protein C and S deficiency usually lead to
      the formation of venous thrombi in clinical practice; however, they rarely lead
      to arterial thrombosis. It has been demonstrated that both protein C and S
      deficiency may lead to myocardial infarctions. However, our literature review
      revealed no reports of left main coronary artery thrombi caused by protein C and
      S deficiency. This paper presents a case of a left main coronary artery thrombus
      resulting from protein C and S deficiency in a young patient with normal coronary
      arteries.

PMID- 23124148
TI  - Pancreatitis with pancreatic tail swelling associated with incretin-based
      therapies detected radiologically in two cases of diabetic patients with end
      stage renal disease.
AB  - We herein report two cases of pancreatitis associated with incretin-based
      therapies in end-stage renal disease (ESRD) patients undergoing dialysis. A 75
      year-old woman with a history of liraglutide use and a 68-year-old man with a
      history of vildagliptin use both presented with nausea. They showed elevated
      levels of pancreatic enzymes and pancreatic tail swelling on CT. Their symptoms
      improved after discontinuing the drugs. In the absence of any obvious secondary
      causes of pancreatitis, we believe that the pancreatitis observed in these cases
      was associated with the incretin-based therapies. Few reports have been published
      on the safety and efficacy of incretin-based therapies in ESRD patients, and it
      remains uncertain whether the changes in the pancreas observed in the present
      cases are characteristic of ESRD patients.

PMID- 23124149
TI  - Successful treatment of serial opportunistic infections including disseminated
      nocardiosis and cryptococcal meningitis in a patient with ANCA-associated
      vasculitis.
AB  - We herein present a case of serial opportunistic infections that included
      disseminated nocardiosis and cryptococcal meningitis in a 67-year-old man who was
      diagnosed with ANCA-associated vasculitis and treated with corticosteroids. Upon
      admission, the initial manifestations of the disease included subcutaneous tumors
      and multiple lesions in the brain and lungs. Nocardia farcinica was identified in
      a culture of the aspirated pus. The patient was successfully treated for
      disseminated nocardiosis with antibiotics. However, three months after discharge,
      he was hospitalized with complaints of nuchal pain. Cryptococcus neoformans was
      identified on a culture of the cerebrospinal fluid. Anti-fungal treatment
      resulted in the remission of cryptococcal meningitis.

PMID- 23124150
TI  - Bronchial asthma developing after 15 years of immunosuppressive treatment
      following renal transplantation.
AB  - A 42-year-old woman who underwent renal transplantation from her mother at the
      age of 26 due to IgA nephropathy had since been treated with immunosuppressive
      agents, including prednisolone (PSL), azathioprine (AZA) and cyclosporine (CsA).
      The patient had remained clinically stable for 15 years. However, in the middle
      of May 2010, she developed bronchial asthma for the first time after performing
      house-cleaning activities and was treated with corticosteroids and antiasthmatic
      agents. The use of immunosuppressive agents as a treatment for severe bronchial
      asthma might have been related to the manifestation of bronchial asthma in this
      case.

PMID- 23124151
TI  - Mixed-type multicentric Castleman's disease developing during a 17-year follow-up
      of sarcoidosis.
AB  - Multicentric Castleman's Disease (MCD) is a systemic disease characterized by
      generalized lymphadenopathy and the proliferation of plasma cells. The
      development of MCD in a patient with preexisting sarcoidosis has not been
      previously reported. We herein describe a case of MCD developing in a 78-year-old
      woman with a 17-year history of sarcoidosis. The patient's serum interleukin-6
      (IL-6) levels were only slightly elevated; however, the IL-6 levels in the fluid
      of both pleural effusion and ascites were markedly elevated. The administration
      of steroid-pulse therapy and prednisolone was ineffective in treating the MCD,
      although treatment with tocilizumab proved highly effective.

PMID- 23124152
TI  - Lymphocyte-depleted Hodgkin lymphoma complicating hemophagocytic
      lymphohistiocytosis as an initial manifestation: a case report and review of the
      literature.
AB  - Hemophagocytic lymphohistocytosis (HLH) is commonly associated with infectious
      diseases or T/NK cell-lymphoma; however that with Hodgkin lymphoma (HL) was
      rarely reported. Herein, we describe a young male diagnosed with lymphocyte
      depleted HL (LD-HL) complicated by HLH as an initial manifestation. He was given
      high-dose steroid therapy plus recombinant thrombomodulin, and subsequent ABVd
      (doxorubicin, bleomycin, vinblastine, dacarbazine) treatment. In spite of the
      achievement of a partial remission treated with one cycle of ABVd, he relapsed
      after 3 cycles. To our knowledge, the present case is very rare, and more
      intensive treatment might be needed for the long-term control of HLH-complicated
      HL.

PMID- 23124153
TI  - Streptococcus sanguis meningitis: report of a case and review of the literature.
AB  - Viridans streptococcus, an indigenous bacterial species of the mouth and
      gastrointestinal tract, is thought to be a rare cause of bacterial meningitis.
      The type of streptococcus involved is important because each type causes a
      different kind of meningitis and is associated with a different outcome. A 39
      year-old previously healthy man was admitted due to the onset of acute purulent
      meningitis. A cerebrospinal fluid culture grew Streptococcus sanguis (S.
      sanguis). Although the patient was asymptomatic for dental caries, odontogenic
      maxillary sinusitis was found to be the cause of the meningitis. Treatment with
      intravenous antibiotics was successful. Following a review of the pertinent
      literature, we discuss the characteristics of S. sanguis meningitis.

PMID- 23124154
TI  - An ocular form of myasthenia gravis with a high titer of anti-MuSK antibodies
      during a long-term follow-up.
AB  - We herein report a case of ocular myasthenia gravis (MG) that was highly positive
      for anti-muscle-specific tyrosine kinase (MuSK) antibodies. The examined patient
      exhibited bilateral ptosis and lateral gaze palsy without any generalized
      symptoms and was diagnosed with ocular MG with anti-MuSK antibodies. She
      responded to treatment with prednisolone and immunosuppressants and experienced
      only ocular symptoms for four years and eight months after onset. Ocular MG with
      anti-MuSK antibodies lasting for a long term has rarely been described. Our
      findings suggest that it may be reasonable to test for the presence of anti-MuSK
      antibodies in patients who present with external ophthalmoplegia.

PMID- 23124155
TI  - Desmopressin-induced posterior reversible encephalopathy syndrome.
AB  - We herein report the case of a patient who presented with an acute decrease of
      visual acuity, hypertension, focal seizures and transient mental dysfunction
      while undergoing desmopressin treatment. Neuroimaging revealed bilateral
      occipital-parietal lesions that presented with vasogenic edema. After controlling
      the hypertension and discontinuing the desmopressin treatment, the patient's
      condition improved. A follow-up imaging examination performed six months later
      showed complete resolution of the lesions. It is important to recognize posterior
      reversible encephalopathy syndrome (PRES) as a rare and serious complication of
      desmopressin administration. Both the blood pressure and water electrolyte
      balance should be carefully monitored in patients receiving desmopressin therapy.

PMID- 23124156
TI  - Staphylococcal enterotoxin B toxic shock syndrome induced by community-acquired
      methicillin-resistant Staphylococcus aureus (CA-MRSA).
AB  - We herein report a case of toxic shock syndrome (TSS) associated with the 2009
      pandemic H1N1 (pH1N1) influenza virus and a community-acquired methicillin
      resistant Staphylococcus aureus (CA-MRSA) infection in a 16-year-old Vietnamese
      girl. Staphylococcal enterotoxin B (SEB) was detected in the patient's serum, and
      the level of anti-SEB antibodies was found to be elevated. A flow cytometric
      analysis showed evidence of activated SEB-reactive Vbeta3+ and Vbeta12+ T cells.
      These data suggest that the CA-MRSA-induced activation of SEB-reactive T cells
      may cause TSS in patients with pH1N1 virus infection. Moreover, this is the first
      report describing immunological confirmation of SEB contributing directly to TSS
      in a patient fulfilling the diagnostic criteria of TSS.

PMID- 23124158
TI  - Hepatic sarcoidosis with an increased serum level of immunoglobulin G4.
AB  - A 70-year-old woman with an increased uptake of 18-Fluorodeoxyglucose (FDG) in
      whole liver on positron emission tomography (PET) was referred to our hospital.
      Laboratory examinations showed increased serum levels of total immunoglobulin G
      (IgG) and IgG4. Gallium scintigraphy showed a remarkable uptake in the liver but
      not in any other organs. On computed tomography (CT) and magnetic resonance
      imaging (MRI), multiple foci of abnormal density were observed in the liver, but
      the pancreas and bile duct lacked any indications of IgG4-related sclerosing
      disease. A liver biopsy specimen revealed multiple non-necrotizing granulomas.
      This is the first report of hepatic sarocidosis in a patient with an elevated
      serum level of IgG4.

PMID- 23124157
TI  - Acquired immune-deficiency syndrome with focal onset of Mycobacterium avium
      infection displaying a histological/genetic pattern of disseminated mycobacteria.
AB  - A 66-year-old man with human immunodeficiency virus (HIV) infection was admitted
      for treatment of Pneumocystis pneumonia. Upon admission, a tumor mass adjacent to
      the thoracic descending aorta was revealed on computed tomography. Histology
      revealed an exudative granuloma with histiocytes packed with numerous acid-fast
      bacilli. Mycobacterium avium was isolated from the tissue. A genetic examination
      of the isolates demonstrated this strain to be located in the cluster consisting
      of strains that cause systemic infection. The patient's baseline CD4+ cell count
      was 9/MUL and the HIV-RNA viral load was 43,800 copies/mL. This case suggests the
      possibility of a localized onset of disseminated M. avium infection.

PMID- 23124159
TI  - Large bilateral isolated internal iliac artery aneurysms.

PMID- 23124160
TI  - Rare complications of systemic lupus erythematosus.

PMID- 23124162
TI  - Design of new arylamino-2-ethane-1,1-diyl- and benzoxazole-2-methylene
      bisphosphonates vs cytotoxicity and chronic inflammation diseases. From
      hydrophobicity prediction to synthesis and biological evaluation.
AB  - A general synthetic approach to two new series of methylenebisphosphonates:
      arylamino-2-ethane-1,1-diyl- and benzoxazole-2-methylenebisphosphonates is
      presented. Acid hydrolysis of selected BPs was undertaken to give the
      corresponding bisphosphonic acid (BP-acid). Next, the prediction of the
      permeability (hydrophobicity) of the target compounds was measured, by a
      combination of RP-HPLC and computational techniques, to study the capacity of
      transporting the molecule through cellular membranes. Cytotoxicity/growth
      inhibition of 50% (GI(50), mg/L) and antichronic inflammation properties of the
      products were evaluated. Later on, a comparison of the pharmacological results
      with water-octanol partition coefficients (log K(OW)) of the compounds was also
      reported.

PMID- 23124161
TI  - Synthesis and biological evaluation of new piplartine analogues as potent aldose
      reductase inhibitors (ARIs).
AB  - As a continuation of our efforts directed towards the development of anti
      diabetic agents from natural sources, piplartine was isolated from Piper chaba,
      and was found to inhibit recombinant human ALR2 with an IC(50) of 160 MUM. To
      improve the efficacy, a series of analogues have been synthesized by modification
      of the styryl/aromatic and heterocyclic ring functionalities of this natural
      product lead. All the derivatives were tested for their ALR2 inhibitory activity,
      and results indicated that adducts 3c, 3e and 2j prepared by the Michael addition
      of piplartine with indole derivatives displayed potent ARI activity, while the
      other compounds displayed varying degrees of inhibition. The active compounds
      were also capable of preventing sorbitol accumulation in human red blood cells.

PMID- 23124163
TI  - Design, synthesis and antibacterial activities of vanillic acylhydrazone
      derivatives as potential beta-ketoacyl-acyl carrier protein synthase III (FabH)
      inhibitors.
AB  - Fatty acid biosynthesis is essential for bacterial survival. FabH, beta-ketoacyl
      acyl carrier protein (ACP) synthase III, is a particularly attractive target,
      since it is central to the initiation of fatty acid biosynthesis and is highly
      conserved among Gram-positive and Gram-negative bacteria. A series of
      acylhydrazone derivatives were synthesized and developed as potent inhibitors of
      FabH. This inhibitor class demonstrates strong broad-spectrum antibacterial
      activity. Compounds with potent antibacterial activities were tested for their
      Escherichia coli FabH inhibitory activity. Especially, compound E9 showed the
      most potent antibacterial activity with MIC values of 0.39-1.56 MUg/mL against
      the tested bacterial strains and exhibited the most potent E. coli FabH
      inhibitory activity with IC(50) of 2.5 MUM. Docking simulation was performed to
      position compound E9 into the E. coli FabH active site to determine the probable
      binding conformation.

PMID- 23124164
TI  - Isolation and characterization of equine amnion mesenchymal stem cells.
AB  - The amnion is a particular tissue whose cells show features of multipotent stem
      cells proposed for use in cellular therapy and regenerative medicine. From equine
      amnion collected after the foal birth we have isolated MSCs (mesenchymal stem
      cells), namely EAMSCs (equine amnion mesenchymal stem cells), from the
      mesoblastic layer. The cells were grown in alpha-MEM (alpha-modified minimum
      essential medium) and the effect of EGF (epidermal growth factor) supplementation
      was evaluated. To assess the growth kinetic of EAMSCs we have taken into account
      some parameters [PD (population doubling), fold increase and DT (doubling time)].
      The differentiation in chondrogenic, adipogenic and osteogenic types of cells and
      their epitope expression by a cytofluorimetric study have been reported. EGF
      supplementation of the culture medium resulted in a significant increase in PD
      growth parameter and in the formation of bone nodules for the osteogenic
      differentiation. By immunohistochemistry the amnion tissue shows a positivity for
      the c-Kit (cluster tyrosine-protein kinase), CD105 and Oct-4 (octamer-binding
      transcription factor 4) antigens that confirmed the presence of MSCs with
      embryonic phenotype.

PMID- 23124165
TI  - Burrowing crab (Neohelice granulata) as a potential bioindicator of heavy metals
      in the Bahia Blanca estuary, Argentina.
AB  - Bioindicators can be used to determine spatial and/or temporal variations of
      heavy metals in a certain coastal or marine environments. This study investigated
      the potential use of the burrowing crab Neohelice granulata from two different
      locations in the Bahia Blanca estuary, a moderately polluted ecosystem.
      Concentrations of zinc (Zn), nickel (Ni), and lead (Pb) in soft tissues of male
      and female crabs were measured. In addition, concentrations of the three metals
      in eggs were compared with concentrations in female crabs. No geographical
      differences were found for any of the three metals, whereas sexual and seasonal
      differences were obtained for Zn and Ni, with the winter season posing lower
      concentrations. Moreover, the three metals were detectable in eggs and were lower
      than concentrations in female crabs (except for Zn). Finally, the usefulness of
      this species as a potential bioindicator of heavy-metal pollution within this
      estuarine ecosystem is discussed.

PMID- 23124166
TI  - Reproductive impairment of a viviparous fish species inhabiting a freshwater
      system with anthropogenic impact.
AB  - The potential threat to animal reproduction by contaminated freshwater systems
      posed the necessity to identify and develop bioindicators and biomarkers to be
      used for screening and evaluation of the effects in organisms. The main goal of
      this work was to determine, through histological analyses and changes in
      gonopodium morphology, whether a freshwater system polluted by anthropogenic
      activities-sewage, agricultural, and industrial-could cause alterations at the
      organ level. We also propose the live-bearing fish, Jenynsia multidentata, as a
      species suitable to study the effects of contaminated aquatic environments. We
      compared male fish sampled at two different stations in Suquia River basin
      (Cordoba, Argentina), both differing in degree of pollution, through liver and
      testis histology and gonopodial morphometric parameters. The water quality, based
      on the physicochemical characteristics of the studied stations, varied markedly
      with a decrease in water quality at the downstream site (station 2). At the
      highest polluted area, detrimental effects on liver and testis were evidenced on
      histological analysis. Male individuals from station 2 also presented noticeable
      structural changes of the anal fin, such as a straight gonopodium and abnormal
      tip area. The present results demonstrate that a freshwater system polluted by
      the impacts of anthropogenic activities has detrimental effects to J.
      multidentata. The alterations registered in individuals from the polluted station
      indicate an impairment of male reproductive performance and imply a risk for
      other live-bearing species as well as the entire biodiversity. We consider J.
      multidentata a sentinel species that is useful to evaluate the potential risk
      present in the studied basin not only to itself but to other species as well.

PMID- 23124167
TI  - Impacts of manganese mining activity on the environment: interactions among soil,
      plants, and arbuscular mycorrhiza.
AB  - The mining district of Molango in the Hidalgo State, Mexico, possesses one of the
      largest deposits of manganese (Mn) ore in the world. This research assessed the
      impacts of Mn mining activity on the environment, particularly the interactions
      among soil, plants, and arbuscular mycorrhiza (AM) at a location under the
      influence of an open Mn mine. Soils and plants from three sites (soil under
      maize, soil under native vegetation, and mine wastes with some vegetation) were
      analyzed. Available Mn in both soil types and mine wastes did not reach toxic
      levels. Samples of the two soil types were similar regarding physical, chemical,
      and biological properties; mine wastes were characterized by poor physical
      structure, nutrient deficiencies, and a decreased number of arbuscular
      mycorrhizal fungi (AMF) spores. Tissues of six plant species accumulated Mn at
      normal levels. AM was absent in the five plant species (Ambrosia psilostachya,
      Chenopodium ambrosoides, Cynodon dactylon, Polygonum hydropiperoides, and
      Wigandia urens) established in mine wastes, which was consistent with the
      significantly lower number of AMF spores compared with both soil types. A.
      psilostachya (native vegetation) and Zea mays showed mycorrhizal colonization in
      their root systems; in the former, AM significantly decreased Mn uptake. The
      following was concluded: (1) soils, mine wastes, and plant tissues did not
      accumulate Mn at toxic levels; (2) despite its poor physical structure and
      nutrient deficiencies, the mine waste site was colonized by at least five plant
      species; (3) plants growing in both soil types interacted with AMF; and (4)
      mycorrhizal colonization of A. psilostachya influenced low uptake of Mn by plant
      tissues.

PMID- 23124168
TI  - Effect of antisense TIMP-1 cDNA on the expression of TIMP-1 and MMP-2 in lung
      tissue with pulmonary fibrosis induced by bleomycin.
AB  - The aim of this study was to observe the effect of antisense tissue inhibitor of
      matrix metalloproteinase-1 (TIMP-1) cDNA on the concentration of hydroxyproline
      (HYP) and the expression of TIMP-1 and matrix metalloproteinase-2 (MMP-2) in the
      lung tissue of rats with bleomycin (BLM)-induced pulmonary fibrosis. Sprague
      Dawley rats were randomly divided into 5 groups: the control, pulmonary fibrosis
      model, sense TIMP-1 transfection, antisense TIMP-1 transfection and empty vector
      transfection groups. For the transfection groups, following the intratracheal
      injection of BLM on days 1, 3, 7, 14, 28 and 60, the rats were treated with
      retroviral vectors and sacrificed on day 28. The control and pulmonary fibrosis
      groups were treated with normal saline at the same time-points. The concentration
      of HYP and the expression levels of TIMP-1 and MMP-2 in the lung tissue were
      detected. The HYP concentration and lung tissue TIMP-1 expression levels of the
      antisense TIMP-1 group decreased significantly on days 1 and 3 compared with
      those of the empty vector and pulmonary fibrosis groups at the same time-points
      (P<0.01), but increased significantly in the sense TIMP-1 group (P<0.01). No
      significant differences were observed in the HYP concentration and TIMP-1
      expression levels in the antisense TIMP-1, sense TIMP-1, empty vector and
      pulmonary fibrosis groups on days 7, 14, 28 and 60. The lung expression levels of
      MMP-2 in all groups, with the exception of the control group, had no significant
      differences at all time-points (P>0.05). Antisense TIMP-1 cDNA retroviral vectors
      are able to suppress the development of pulmonary fibrosis in the early stages. 

PMID- 23124169
TI  - Synthesis of 5-halogenated 1,2,3-triazoles under stoichiometric Cu(I)-mediated
      azide-alkyne cycloaddition (CuAAC or 'Click Chemistry').
AB  - Glucosylated heterocycles have been identified as potent inhibitors of glycogen
      phosphorylase (GP), a biomolecular target for the treatment of hyperglycemia and
      therefore type 2 diabetes. Several glucosylated triazoles have been evaluated as
      GP inhibitors and additional structures are being considered in the present study
      with the introduction of a substituent at the 5-position of the triazole ring.
      The 1,3-dipolar cycloaddition of azide and alkyne using stoichiometric amounts of
      Cu(I) halides favored the formation of the 5-halogenated 1,2,3-triazoles. The
      influence of the copper halide introduced (CuI, CuBr, or CuCl) provided different
      results and more specifically for the CuCl system which afforded a dimeric 5,5'
      bistriazole in good yield (56%) as evidenced by crystallographic data.

PMID- 23124170
TI  - Schischkiniin support studies: synthetic access to 1,1'-bisindoles.
AB  - The first general synthetic approach to 1,1'-bisindoles is described. Two
      simultaneous, ambient temperature Mori-Ban reactions were used to effect
      bisindolization of several diallylated hydrazobenzenes with minimal cleavage of
      the N-N bond.

PMID- 23124171
TI  - Electrochemical impedance measurement of a carbon nanotube probe electrode.
AB  - We measured and analyzed the electrochemical impedance of carbon nanotube (CNT)
      probe electrodes fabricated through the physical separation of insulated CNT
      bridges. The fabricated CNT electrodes were free-standing CNTs that were
      completely covered with an insulator, except for their tips. Typical dimensions
      of the nanoelectrodes were 1-10 nm in CNT diameter, 80-300 nm in insulator
      diameter, 0.5-4 MUm in exposed CNT length and 1-10 MUm in probe length. The
      electrochemical impedance at frequencies ranging from 40 Hz to 1 MHz was measured
      in physiological saline. The measured impedance of the CNT electrode was constant
      at 32 MOmega at frequencies below 1 kHz and was inversely proportional to
      frequency at frequencies above 10 kHz. By means of comparison with the parasitic
      capacitive impedance of the insulator membrane, we confirmed that the electrode
      was sufficiently insulated such that the measured constant impedance was given by
      the exposed CNT tip. Consequently, we can use the CNT electrode for highly
      localized electrochemical impedance measurements below 1 kHz. Considering an
      equivalent circuit and the nanoscopic dimensions of the CNT electrode, we
      demonstrated that the constant impedance was governed by diffusion impedance,
      whereas the solution resistance, charge-transfer resistance and double-layer
      capacitance were negligible.

PMID- 23124172
TI  - Bipolar disorder: its explosion vs. research funding.

PMID- 23124173
TI  - Recording past experiences:  a qualitative study of how patients and family
      members adjust to the diagnosis of bipolar disorder.
AB  - Few studies have investigated the processes associated with patients' reactions
      to the diagnosis of biopolar disorder, yet assisting patients to develop an
      acceptance of the condition is a core component of effective psychosocial
      interventions. This study explored the views and experiences of patients and
      family members about receiving a diagnosis of bipolar disorder and its
      implications for the future. We interviewed 17 people with bipolar disorder (7
      diagnosed within the previous 12 months, 10 diagnosed 3-5 years ago), as well as
      9 family members. Using the Phenomenology and Lived Experience framework to
      analyze the interview transcripts, we identified 3 key themes: (1) Misdiagnosis
      and growing awareness; (2) Accepting the diagnosis (including initial reactions
      and adjusting to the diagnosis); and (3) Factors that may have facilitated an
      earlier acceptance. From the findings, we draw implications for clinicians.

PMID- 23124174
TI  - The sorry state of treatment research in bipolar disorder: an ongoing but
      preventable catastrophe.

PMID- 23124175
TI  - Burden, rewards, and coping--the ups and downs of caregivers of people with
      mental illness.
AB  - Besides burden, we need to examine potential rewards of caregiving and coping
      strategies to determine effective means of supporting caregivers of people with
      mental illness. Therefore, we conducted semistructured interviews with 60
      caregivers of patients with mental illness and analyzed the transcripts with a
      summarizing content analysis. The interviews focused on negative and positive
      aspects of providing care and on coping strategies; the latter was also evaluated
      with the Freiburg Questionnaire on Coping with Illness. The caregivers named 787
      individual statements of burden and 413 individual statements of rewards. A
      factor analysis of the rewards identified growth in character as the main factor.
      The items with the highest factor loading are increase in self-confidence, inner
      strength, maturity, and life experience. Linear regression and regression tree
      analysis identified predictors for caregiver burden. To effectively reduce the
      burden on caregivers, we need knowledge about their concrete burdens. However, to
      optimize resource orientation, we must also pay much more attention to the
      potential rewards of caring.

PMID- 23124176
TI  - Social distance and stigma toward individuals with schizophrenia: findings in an
      urban, African-American community sample.
AB  - Because schizophrenia is arguably among the most stigmatized health conditions,
      research assessing correlates of stigma is essential. This study examined factors
      associated with stigma in predominantly Protestant, low-income, urban African
      Americans in the Southeastern United States. A survey was distributed to 282
      patrons of an inner-city food court/farmers' market. Associations were assessed
      between two measures of stigma--an adapted version of the Social Distance Scale
      (SDS) and a Semantic Differential Measure (SDM) of attributes such as
      dangerousness, dirtiness, and worthlessness--and several key variables addressing
      sociodemographic characteristics and exposure to/familiarity with mental
      illnesses. Independent predictors of scores on the two measures were identified
      using linear regression modeling. Higher stigma (as measured by the SDM) was
      predicted by a family history of psychiatric treatment, whereas lower stigma (as
      indicated by the SDS) was predicted by personal psychiatric treatment history and
      higher annual income. The results suggest special considerations when working
      with disenfranchised populations, especially family members of individuals with
      mental illnesses, in treatment settings.

PMID- 23124177
TI  - Psychosocial functioning and cognitive deficits are not associated with membrane
      bound catechol-O-methyltransferase deoxyribonucleic acid methylation in siblings
      of patients with schizophrenia.
AB  - In this study, we investigated whether the siblings of patients with
      schizophrenia have deficits in cognition and psychosocial functioning and whether
      the psychosocial functioning and cognitive deficits correlate with the
      methylation status of the membrane-bound catechol-O-methyltransferase (MB-COMT)
      gene in peripheral leukocytes. Cognitive abilities were evaluated using the
      attention/vigilance Continuous Performance Test, delayed/immediate recall scores,
      the Wisconsin Card Sorting Test, and the Semantic Verbal Fluency Test.
      Psychosocial functioning was evaluated using the Scale for the Assessment of
      Negative Symptoms, the Global Assessment of Functioning scale, and the Social
      Adjustment Scale. A bisulfate-based sequencing was adopted to analyze the
      methylation status of the MB-COMT promoter in peripheral leukocytes. Significant
      impairments in attention/vigilance and verbal memory and significant decreases in
      immediate and delayed recall scores were observed in the siblings of patients
      with schizophrenia compared with the healthy subjects. In addition, significant
      deficits in global social functioning and in social interaction were found in the
      siblings. The tested region of the MB-COMT promoter was generally unmethylated in
      peripheral leukocytes, without significant correlation with behavioral deficits
      in the siblings.Our study demonstrated that the siblings have significant
      deficits in cognition and psychosocial functioning, which may not be associated
      with MB-COMT methylation in peripheral leukocytes.

PMID- 23124178
TI  - The effectiveness of solution-focused therapy and short- and long-term
      psychodynamic psychotherapy on self-concept during a 3-year follow-up.
AB  - This study compares the effectiveness of solution-focused therapy (SFT) and short
      and long-term psychodynamic psychotherapy (SPP and LPP) on self-concept during a
      3-year follow-up. Altogether, 326 patients with mood or anxiety disorder were
      randomized to SFT, SPP, and LPP in the Helsinki Psychotherapy Study. Outcome was
      assessed using the Structural Analysis of Social Behavior questionnaire at
      baseline and 7, 12, 24, and 36 months after. Overall, during the first year of
      follow-up, self-concept improved more in both SFT and SPP than in LPP, indicated
      by the primary outcome indicators self-directed affiliation (AF) and self
      directed autonomy, as well as by most of the eight secondary cluster scores.
      After the 3-year follow-up, LPP was more effective than SFT in AF and in the
      cluster scores self-affirm, self-blame, and self-neglect, whereas no difference
      was noted between LPP and SPP. Long duration and psychodynamic orientation of
      therapy may be beneficial for self-concept improvement.

PMID- 23124179
TI  - Lifetime polytraumatization in adolescence and being a victim of bullying.
AB  - The purposes of this study were to examine the mental health consequences of
      having been a victim of bullying and to investigate whether the impact of
      bullying was dependent on the co-occurrence of other potentially traumatic
      events, noninterpersonal traumas, interpersonal traumas, as well as adverse
      childhood circumstances. A community sample of participants (n = 462; 216 males
      and 246 females) aged 15 to 20 years completed the self-administered Linkoping's
      Youth Life Experience Scale about lifetime exposure to a range of traumatic and
      other adverse events and circumstances and the Trauma Symptom Checklist for
      Children (TSCC). The results showed that those who reported being a victim of
      bullying reported significantly higher scores on all TSCC clinical scales as well
      as significantly more other traumatic and adverse family exposures. Multiple
      linear regression analyses indicated that the impact of bullying on mental health
      was explained, to a considerable degree, by the accumulation of other adverse and
      traumatic exposures, particularly in the females.

PMID- 23124180
TI  - Recalled peritraumatic distress in survivors of violent crime: exploring its
      impact on the relationship between posttraumatic stress disorder symptoms and
      posttraumatic growth.
AB  - Several authors have speculated that the lack of consistency regarding the
      relationship between symptoms of posttraumatic stress disorder (PTSD) and
      posttraumatic growth (PTG) is caused by third variables. Recalled peritraumatic
      distress (PD) may operate as a third variable because previous research suggests
      that both PTSD and PTG correlate with recalled PD. Therefore, the present study
      explored how recalled PD impacts the relationship between PTSD and PTG. An
      Internet questionnaire on PTSD symptom severity, recalled PD, and PTG was
      administered to 678 survivors of violent crime. The results suggested that
      recalled PD suppresses the association between PTSD symptom severity and PTG. In
      addition, a significant association between the interaction term of PTSD symptom
      severity and recalled PD and PTG was observed. Simple slopes tests indicated that
      self-reported PTSD symptoms were negatively associated with PTG but only among
      survivors with high levels of PD.

PMID- 23124181
TI  - Comparing the symptoms of posttraumatic stress disorder with the distress and
      fear disorders.
AB  - New theoretical models of mood and anxiety disorders have been proposed to better
      understand the relations and patterns leading to their high diagnostic
      comorbidities. These models have highlighted two new groupings of the disorders,
      focused on the prevalence of fear and distress symptoms. The present study
      investigated the fit of the symptoms of posttraumatic stress disorder (PTSD) in
      these new models. The relations between the two primary sets of symptom scales of
      PTSD and the diagnoses of other comorbid disorders were examined in a large
      multisite sample of veterans from primary care clinics. The results suggested
      that there was no reliable difference in the predictive power of any of the PTSD
      symptom scales across the two diagnostic groups. New transdiagnostic models,
      assessment practices, and treatment approaches may provide better understanding
      of symptom overlap and diagnostic comorbidity in PTSD and related disorders.

PMID- 23124182
TI  - Temperament and character of young male conscripts with adjustment disorder: a
      case-control study.
AB  - Personality is an important clinical factor for successful adjustment in
      stressful situations. The aim of this study was to examine possible differences
      in temperament and character dimensions between patients with adjustment disorder
      with depressed mood and healthy controls. Among the young male conscripts, 86
      subjects with adjustment disorder with depressed mood and 86 healthy controls
      were included. The mean scores in the 7 dimensions and 25 subscales of the
      Temperament and Character Inventory were compared between the patients with
      adjustment disorder with depressed mood and the control group by an independent t
      test. The patients with adjustment disorder with depressed mood had significantly
      higher scores on harm-avoidance and lower scores on self-directedness,
      cooperativeness, and self-transcendence than did the controls. There were no
      differences in novelty seeking, reward dependence, and persistence in temperament
      between the two groups. The results of this study suggest that the personality
      traits of the subjects with adjustment disorder with depressed mood would make
      them vulnerable to stressful situations and less skilled in coping with
      conscription.

PMID- 23124183
TI  - Assessment of risk factors related to suicide attempts in patients with bipolar
      disorder.
AB  - We compared the characteristics of patients with bipolar disorder with and
      without a history of suicide attempts to identify the risk factors of suicide in
      this disorder. Among 212 patients with bipolar disorder, 44 (21.2%) patients had
      histories of suicide attempts. Suicide attempters were younger and more likely to
      be diagnosed with bipolar II. The variables that differentiated those who did
      from those who did not attempt suicide included age at first contact, lifetime
      history of antidepressant use, major depressive episode, mixed episode, auditory
      hallucinations, rapid cycling, the number of previous mood episodes, age of first
      depressive episode, and age of first psychotic symptoms. Strong predictors of
      suicide attempts were younger age at onset, lifetime history of auditory
      hallucinations, and history of antidepressant use. Antecedent depressive episodes
      and psychotic symptoms predicted the first suicide attempt in patients with
      bipolar disorder. This study could help clinicians to understand the major risk
      factors of suicidal behavior in bipolar disorder.

PMID- 23124184
TI  - Persistence of "past-life" memories in adults who, in their childhood, claimed
      memories of a past life.
AB  - This article tests the consistency and the continuation of alleged "past-life"
      memories from childhood into adulthood and the possible detrimental effects of
      such childhood memories on the development into adult life. Twenty-eight adults
      aged 28 to 56 years who had claimed to have memories of a past life when they
      were children were interviewed in Lebanon. Their memories had been recorded when
      they were children, at the mean age of 6 years. Of the 28 participants, 24 still
      reported some past-life memories, whereas 4 had forgotten everything. Twenty-one
      were sure that their memories were a continuation of their past-life memories in
      childhood, whereas three were unsure about it. For those who were sure of still
      having genuine past-life memories, the mean number of statements about the past
      life fell from 30, as children, to 4, as adults. Only half of the currently
      reported statements were reported when the participants were interviewed as
      children, raising the question of false and distorted memories. There were no
      indications that the past-life memories had a detrimental effect on the
      participants' development into adulthood. They were all leading normal active
      lives.

PMID- 23124185
TI  - Facets of perfectionism in a sample of hypersexual patients.
AB  - This study investigated the role of perfectionism in a treatment-seeking sample
      (N = 136) of adult men and women using the Perfectionism Inventory (PI) and the
      Hypersexual Behavior Inventory (HBI). Several facets of perfectionism were
      positively correlated with hypersexuality, with the concern over mistakes scale
      from the PI accounting for most of the predictive variance in patterns of
      hypersexual behavior measured by the HBI. Items associated with concern over
      mistakes closely parallel the construct of shame noted in other studies of
      hypersexual patients. To a lesser degree, the PI scale planfulness also showed a
      negative relationship with hypersexuality, suggesting tendencies of impulsivity
      in the current patients. These data reinforce the findings in other studies that
      patterns of harsh self-criticism and impulsivity seem to strongly influence
      hypersexual behavior.

PMID- 23124186
TI  - Telescoping phenomenon in pathological gambling: association with gender and
      comorbidities.
AB  - The course of pathological gambling (PG) in women has been described as having a
      later age of initiation but a shorter time to problematic gambling
      ("telescoped"). This study examined evidence for telescoping and its relationship
      with comorbidities. Seventy-one treatment-seeking individuals with PG underwent a
      diagnostic interview to examine gambling behaviors, age at initiation of
      gambling, and time from initiation to meeting criteria for PG. The women had a
      higher mean age at gambling initiation compared with that of the men (mean [SD]
      age, 31.3 [13.0] years, compared with 22.4 [7.9] years; p = 0.0003) and a
      significantly shorter time from initiation of gambling to meeting the criteria
      for PG (8.33 [8.7] years compared with 11.97 [9.1] years; p = 0.0476) after
      controlling for demographic and clinical variables. This study presents evidence
      for a gender-specific course of PG unrelated to psychiatric comorbidities and
      suggests a need for greater clinical focus on the gender differences of gambling
      behavior.

PMID- 23124187
TI  - Mindfulness-based stress reduction for comorbid anxiety and depression: case
      report and clinical considerations.
AB  - Growing research literature has documented the effectiveness of mindfulness-based
      interventions for anxiety and depressive disorders. Mindfulness-based stress
      reduction (MBSR) teaches a series of mindfulness meditation and yoga practices,
      delivered in a group format during eight weekly sessions plus one full-day
      session. This case report demonstrates how MBSR was associated with dramatic
      clinical improvement of an individual with symptoms of panic, generalized
      anxiety, and depression. Scores on clinical assessment measures suggested
      clinically severe levels of anxious arousal, generalized anxiety, worry, fear of
      negative evaluation, and depression at the beginning of the intervention. The
      scores on all these measures fell well within normal limits 7 weeks later at the
      end of the intervention, and no remaining symptoms were reported afterward.
      Increased life satisfaction and quality of life were documented as well. This
      case illustrates the potential benefit of MBSR as an alternative or adjunctive
      treatment for comorbid anxiety and depressive disorder symptoms.

PMID- 23124188
TI  - Disturbance of SHH signalling pathway during early embryogenesis in the cadmium
      induced omphalocele chick model.
AB  - INTRODUCTION: Administration of cadmium (Cd) after 60 h (H) incubation induces
      ventral body wall defect (VBWD) similar to the omphalocele phenotype in the chick
      embryo. In this model, the earliest histological changes have been observed in
      somites commencing at 4-h post-treatment (4H). The molecular mechanism by which
      Cd acts in this critical period of embryogenesis still remains unclear. Sonic
      hedgehog (SHH) signalling plays an important role in vertebrate development,
      including somitogenesis and thus ventral body wall formation. Patched (PTCH), a
      cell membrane receptor for SHH, is expressed in somites and Patched knockout mice
      display somite dysfunction. Another transmembrane receptor, Smoothened (SMO), is
      also expressed in somites and transduces the SHH signal regulated by PTCH. We
      designed this study to test the hypothesis that SHH signalling is downregulated
      during the critical period of early embryogenesis in the Cd-induced omphalocele
      chick model. METHODS: After 60 h of incubation, chicks were exposed to either
      chick saline or 50 MUL of 50 MUM cadmium acetate and divided into two groups:
      control and Cd (n = 24 for each group). Chicks were harvested 1, 4, and 8 h post
      treatment. Real-time RT-PCR was performed to evaluate the relative mRNA
      expression level of SHH, PTCH and SMO. Immunofluorescence confocal microscopy was
      then performed to evaluate protein expression/distribution of SHH, PTCH and SMO.
      RESULTS: The relative mRNA expression levels of SHH, PTCH and SMO were
      significantly downregulated in the Cd group compared to controls at 4H post
      treatment, whereas, there were no significant differences at the other time
      points. Immunohistochemistry revealed that the intensity of SHH, PTCH and SMO was
      markedly diminished at 4 h in Cd-treated embryos compared to controls.
      CONCLUSION: Disturbance of the SHH signalling pathway as evidenced by SHH, PTCH
      and SMO downregulation during the narrow window of early embryogenesis may result
      in somite maldevelopment, contributing to the omphalocele phenotype in the Cd
      chick model.

PMID- 23124191
TI  - Marinilabilia nitratireducens sp. nov., a lipolytic bacterium of the family
      Marinilabiliaceae isolated from marine solar saltern.
AB  - A Gram-negative, rod shaped, motile bacterium, was isolated from a marine solar
      saltern sample collected from Kakinada, India. Strain AK2(T) was determined to be
      positive for nitrate reduction, catalase, Ala-Phe-Pro-arylamidase, beta
      galactosidase, beta-N-acetylglucosaminidase, beta-glucosidase, beta-xylosidase,
      alpha-glucosidase, alpha-galactosidase and phosphatase activities, hydrolysis of
      aesculin, Tween 20/40/60/80 and urea. It was determined to be negative for
      oxidase, lysine decarboxylase and ornithine decarboxylase activities and could
      not hydrolyze agar, casein, gelatin and starch. The predominant fatty acids were
      identified as iso-C(15:0) (28.2 %), anteiso-C(15:0) (23.2 %), iso-C(13:0) (19.9
      %) and iso-C(15:0) 3-OH (13.9 %). Strain AK2(T) was found to contain menaquinone
      with seven isoprene units (MK-7) as the sole respiratory quinone and
      phosphatidylethanolamine, one unidentified phospholipid and three unidentified
      lipids as polar lipids. The 16S rRNA gene sequence analysis indicated the strain
      AK2(T) as a member of the genus Marinilabilia and is closely related to
      Marinilabilia salmonicolor with pair-wise sequence similarity of 98.2 %.
      Phylogenetic analysis of 16S rRNA gene revealed that the strain AK2(T) clustered
      with M. salmonicolor. However, DNA-DNA hybridization with M. salmonicolor JCM
      21150(T) showed a relatedness of 48 +/- 0.5 % with respect to strain AK2(T). The
      DNA G+C content of the strain was determined to be 40.2 mol%. Based on the
      phenotypic characteristics and phylogenetic inference, it is proposed that the
      strain AK2(T) represents a novel species of the genus Marinilabilia, for which
      the name Marinilabilia nitratireducens sp. nov. is proposed. The type strain of
      M. nitratireducens sp. nov. is AK2(T) (= MTCC 11402(T) = JCM 17679(T)).

PMID- 23124189
TI  - LOX-1 in atherosclerosis: biological functions and pharmacological modifiers.
AB  - Lectin-like oxidized LDL (oxLDL) receptor-1 (LOX-1, also known as OLR-1), is a
      class E scavenger receptor that mediates the uptake of oxLDL by vascular cells.
      LOX-1 is involved in endothelial dysfunction, monocyte adhesion, the
      proliferation, migration, and apoptosis of smooth muscle cells, foam cell
      formation, platelet activation, as well as plaque instability; all of these
      events are critical in the pathogenesis of atherosclerosis. These LOX-1-dependent
      biological processes contribute to plaque instability and the ultimate clinical
      sequelae of plaque rupture and life-threatening tissue ischemia. Administration
      of anti-LOX-1 antibodies inhibits atherosclerosis by decreasing these cellular
      events. Over the past decade, multiple drugs including naturally occurring
      antioxidants, statins, antiinflammatory agents, antihypertensive and
      antihyperglycemic drugs have been demonstrated to inhibit vascular LOX-1
      expression and activity. Therefore, LOX-1 represents an attractive therapeutic
      target for the treatment of human atherosclerotic diseases. This review aims to
      integrate the current understanding of LOX-1 signaling, regulation of LOX-1 by
      vasculoprotective drugs, and the importance of LOX-1 in the pathogenesis of
      atherosclerosis. 

PMID- 23124192
TI  - Atraumatic dislocation of the lunate: floating lunate syndrome.

PMID- 23124190
TI  - Alpha-synuclein elicits glucose uptake and utilization in adipocytes through the
      Gab1/PI3K/Akt transduction pathway.
AB  - Insulin is the main glucoregulator that promotes the uptake of glucose by tissues
      and the subsequent utilization of glucose as an energy source. In this paper, we
      describe a novel glucoregulator, the alpha-synuclein (SNCA) protein, that has
      previously been linked to Parkinson's disease. Treatment with recombinant SNCA
      promotes glucose uptake in vitro in preadipocytes and in vivo in the adipose
      tissues and skeletal muscles of mice through the LPAR2/Gab1/PI3K/Akt pathway;
      these effects occur independently of the insulin receptor. This function of SNCA
      represents a new mechanistic insight that creates novel avenues of research with
      respect to the process of glucose regulation.

PMID- 23124193
TI  - Exome-based linkage disequilibrium maps of individual genes: functional
      clustering and relationship to disease.
AB  - Exome sequencing identifies thousands of DNA variants and a proportion of these
      are involved in disease. Genotypes derived from exome sequences provide
      particularly high-resolution coverage enabling study of the linkage
      disequilibrium structure of individual genes. The extent and strength of linkage
      disequilibrium reflects the combined influences of mutation, recombination,
      selection and population history. By constructing linkage disequilibrium maps of
      individual genes, we show that genes containing OMIM-listed disease variants are
      significantly under-represented amongst genes with complete or very strong
      linkage disequilibrium (P = 0.0004). In contrast, genes with disease variants are
      significantly over-represented amongst genes with levels of linkage
      disequilibrium close to the average for genes not known to contain disease
      variants (P = 0.0038). Functional clustering reveals, amongst genes with
      particularly strong linkage disequilibrium, significant enrichment of essential
      biological functions (e.g. phosphorylation, cell division, cellular transport and
      metabolic processes). Strong linkage disequilibrium, corresponding to reduced
      haplotype diversity, may reflect selection in utero against deleterious mutations
      which have profound impact on the function of essential genes. Genes with very
      weak linkage disequilibrium show enrichment of functions requiring greater
      allelic diversity (e.g. sensory perception and immune response). This category is
      not enriched for genes containing disease variation. In contrast, there is
      significant enrichment of genes containing disease variants amongst genes with
      more average levels of linkage disequilibrium. Mutations in these genes may less
      likely lead to in utero lethality and be subject to less intense selection.

PMID- 23124194
TI  - Exposures to endocrine-disrupting chemicals and age of menarche in adolescent
      girls in NHANES (2003-2008).
AB  - BACKGROUND: The observed age of menarche has fallen, which may have important
      adverse social and health consequences. Increased exposure to endocrine
      disrupting compounds (EDCs) has been associated with adverse reproductive
      outcomes. OBJECTIVE: Our objective was to assess the relationship between EDC
      exposure and the age of menarche in adolescent girls. METHODS: We used data from
      female participants 12-16 years of age who had completed the reproductive health
      questionnaire and laboratory examination for the Centers for Disease Control and
      Prevention's National Health and Nutrition Examination Survey (NHANES) for years
      2003-2008 (2005-2008 for analyses of phthalates and parabens). Exposures were
      assessed based on creatinine-corrected natural log urine concentrations of
      selected environmental chemicals and metabolites found in at least 75% of samples
      in our study sample. We used Cox proportional hazards analysis in SAS 9.2 survey
      procedures to estimate associations after accounting for censored data among
      participants who had not reached menarche. We evaluated body mass index (BMI;
      kilograms per meter squared), family income-to-poverty ratio, race/ethnicity,
      mother's smoking status during pregnancy, and birth weight as potential
      confounders. RESULTS: The weighted mean age of menarche was 12.0 years of age.
      Among 440 girls with both reproductive health and laboratory data, after
      accounting for BMI and race/ethnicity, we found that 2,5-dichlorophenol (2,5-DCP)
      and summed environmental phenols (2,5-DCP and 2,4-DCP) were inversely associated
      with age of menarche [hazard ratios of 1.10; 95% confidence interval (CI): 1.01,
      1.19 and 1.09; 95% CI: 1.01, 1.19, respectively]. Other exposures (total
      parabens, bisphenol A, triclosan, benzophenone-3, total phthalates, and 2,4-DCP)
      were not significantly associated with age of menarche. CONCLUSIONS: Our findings
      suggest an association between 2,5-DCP, a potential EDC, and earlier age of
      menarche in the general U.S. population.

PMID- 23124195
TI  - Bilateral foveal cysts secondary to Streptococcus constellatus endocarditis.
AB  - Infective endocarditis can be acute or subacute, depending on the virulence of
      the causative organism. It can also cause loss of vision by a variety of
      mechanisms, ranging from embolic retinal artery occlusion to endogenous
      endophthalmitis. We illustrate the first report of foveal cyst formation
      secondary to infective endocarditis. A 53-year-old man presented to his general
      practitioner with a variety of constitutional symptoms, but initial laboratory
      and imaging investigations revealed only mild normocytic anaemia, and he was
      discharged from further medical care. Four weeks later he developed bilateral
      visual loss associated with whitish lesions of the superficial retina at both
      foveae. These later developed into foveal cysts with disruption of the
      photoreceptor inner segment-outer segment junction and persistent poor visual
      acuity of 6/60 OU. No retinal haemorrhages or Roth spots were noted. Only after
      he presented with visual loss did further investigations reveal the underlying
      diagnosis of streptococcal endocarditis. Ophthalmologists assessing retinal
      pathology which presents in association with undiagnosed constitutional symptoms
      are advised to refer such patients promptly for thorough medical investigation,
      including blood culture and echocardiography where appropriate.

PMID- 23124196
TI  - Clinical characteristics of high grade foveal hypoplasia.
AB  - To report clinical characteristics of high grade foveal hypoplasia. Patients with
      foveal hypoplasia of grade 3 or 4 on spectral domain optical coherence tomography
      according to a previously published scheme were enrolled. All patients underwent
      a full ophthalmologic assessment including visual acuity testing, slit lamp
      biomicroscopy, fundus examination, and evaluation of ocular alignment. The
      underlying causes of foveal hypoplasia were identified as albinism in five
      patients and aniridia in six patients. The mean logMAR visual acuity was 0.57 +/-
      0.24 (range 0.22-1.00) in the right eyes and 0.58 +/- 0.21 (range 0.30-1.00) in
      the left eyes. On fundus examination in patients with albinism, two patients
      showed marked transparency, one patient showed moderate transparency, and two
      patients showed minimal transparency. Among six patients with aniridia, five
      patients showed normal macular pigmentation without macular reflex and one
      patient showed decreased macular pigmentation with no macular reflex. Patients
      with high grade macular hypoplasia tended to have poor visual acuities; however,
      the range of visual acuity was quite variable. Other factors associated with
      underlying disease could be the reason of this variability. Therefore, careful
      consideration should be given when assessing visual prognosis in foveal
      hypoplasia using optical coherence tomography.

PMID- 23124197
TI  - Medical error: the second victim.

PMID- 23124198
TI  - Dix-Hallpike and Epley manoeuvres.

PMID- 23124199
TI  - The adult tracheostomy: a guide  for the hospital at night doctor.

PMID- 23124200
TI  - Managing airway obstruction.

PMID- 23124201
TI  - Localization and substrate selectivity of sea urchin multidrug (MDR) efflux
      transporters.
AB  - In this study, we cloned, expressed and functionally characterized
      Stronglycentrotus purpuratus (Sp) ATP-binding cassette (ABC) transporters. This
      screen identified three multidrug resistance (MDR) transporters with functional
      homology to the major types of MDR transporters found in humans. When
      overexpressed in embryos, the apical transporters Sp-ABCB1a, ABCB4a, and ABCG2a
      can account for as much as 87% of the observed efflux activity, providing a
      robust assay for their substrate selectivity. Using this assay, we found that sea
      urchin MDR transporters export canonical MDR susbtrates such as calcein-AM,
      bodipy-verapamil, bodipy-vinblastine, and mitoxantrone. In addition, we
      characterized the impact of nonconservative substitutions in the primary
      sequences of drug binding domains of sea urchin versus murine ABCB1 by mutation
      of Sp-ABCB1a and treatment of embryos with stereoisomeric cyclic peptide
      inhibitors (QZ59 compounds). The results indicated that two substitutions in
      transmembrane helix 6 reverse stereoselectivity of Sp-ABCB1a for QZ59 enantiomers
      compared with mouse ABCB1a. This suggests that subtle changes in the primary
      sequence of transporter drug binding domains could fine-tune substrate
      specificity through evolution.

PMID- 23124202
TI  - The human W42R gammaD-crystallin mutant structure provides a link between
      congenital and age-related cataracts.
AB  - Some mutants of human gammaD-crystallin are closely linked to congenital
      cataracts, although the detailed molecular mechanisms of mutant-associated
      cataract formation are generally not known. Here we report on a recently
      discovered gammaD-crystallin mutant (W42R) that has been linked to autosomal
      dominant, congenital cataracts in a Chinese family. The mutant protein is much
      less soluble and stable than wild-type gammaD-crystallin. We solved the crystal
      structure of W42R at 1.7 A resolution, which revealed only minor differences from
      the wild-type structure. Interestingly, the W42R variant is highly susceptible to
      protease digestion, suggesting the presence of a small population of partially
      unfolded protein. This partially unfolded species was confirmed and quantified by
      NMR spectroscopy. Hydrogen/deuterium exchange experiments revealed chemical
      exchange between the folded and unfolded species. Exposure of wild-type gammaD
      crystallin to UV caused damage to the N-terminal domain of the protein, resulting
      in very similar proteolytic susceptibility as observed for the W42R mutant.
      Altogether, our combined data allowed us to propose a model for W42R
      pathogenesis, with the W42R mutant serving as a mimic for photodamaged gammaD
      crystallin involved in age-related cataract.

PMID- 23124203
TI  - Structural basis for galectin-1-dependent pre-B cell receptor (pre-BCR)
      activation.
AB  - During B cell differentiation in the bone marrow, the expression and activation
      of the pre-B cell receptor (pre-BCR) constitute crucial checkpoints for B cell
      development. Both constitutive and ligand-dependent pre-BCR activation modes have
      been described. The pre-BCR constitutes an immunoglobulin heavy chain (IgMU) and
      a surrogate light chain composed of the invariant lambda5 and VpreB proteins. We
      previously showed that galectin-1 (GAL1), produced by bone marrow stromal cells,
      is a pre-BCR ligand that induces receptor clustering, leading to efficient pre
      BII cell proliferation and differentiation. GAL1 interacts with the pre-BCR via
      the unique region of lambda5 (lambda5-UR). Here, we investigated the solution
      structure of a minimal lambda5-UR motif that interacts with GAL1. This motif
      adopts a stable helical conformation that docks onto a GAL1 hydrophobic surface
      adjacent to its carbohydrate binding site. We identified key hydrophobic residues
      from the lambda5-UR as crucial for the interaction with GAL1 and for pre-BCR
      clustering. These residues involved in GAL1-induced pre-BCR activation are
      different from those essential for autonomous receptor activation. Overall, our
      results indicate that constitutive and ligand-induced pre-BCR activation could
      occur in a complementary manner.

PMID- 23124204
TI  - A refined analysis of superoxide production by mitochondrial sn-glycerol 3
      phosphate dehydrogenase.
AB  - The oxidation of sn-glycerol 3-phosphate by mitochondrial sn-glycerol 3-phosphate
      dehydrogenase (mGPDH) is a major pathway for transfer of cytosolic reducing
      equivalents to the mitochondrial electron transport chain. It is known to
      generate H(2)O(2) at a range of rates and from multiple sites within the chain.
      The rates and sites depend upon tissue source, concentrations of glycerol 3
      phosphate and calcium, and the presence of different electron transport chain
      inhibitors. We report a detailed examination of H(2)O(2) production during
      glycerol 3-phosphate oxidation by skeletal muscle, brown fat, brain, and heart
      mitochondria with an emphasis on conditions under which mGPDH itself is the
      source of superoxide and H(2)O(2). Importantly, we demonstrate that a substantial
      portion of H(2)O(2) production commonly attributed to mGPDH originates instead
      from electron flow through the ubiquinone pool into complex II. When complex II
      is inhibited and mGPDH is the sole superoxide producer, the rate of superoxide
      production depends on the concentrations of glycerol 3-phosphate and calcium and
      correlates positively with the predicted reduction state of the ubiquinone pool.
      mGPDH-specific superoxide production plateaus at a rate comparable with the other
      major sites of superoxide production in mitochondria, the superoxide-producing
      center shows no sign of being overreducible, and the maximum superoxide
      production rate correlates with mGPDH activity in four different tissues. mGPDH
      produces superoxide approximately equally toward each side of the mitochondrial
      inner membrane, suggesting that the Q-binding pocket of mGPDH is the major site
      of superoxide generation. These results clarify the maximum rate and mechanism of
      superoxide production by mGPDH.

PMID- 23124205
TI  - Staurosporines disrupt phosphatidylserine trafficking and mislocalize Ras
      proteins.
AB  - Oncogenic mutant Ras is frequently expressed in human cancers, but no anti-Ras
      drugs have been developed. Since membrane association is essential for Ras
      biological activity, we developed a high content assay for inhibitors of Ras
      plasma membrane localization. We discovered that staurosporine and analogs
      potently inhibit Ras plasma membrane binding by blocking endosomal recycling of
      phosphatidylserine, resulting in redistribution of phosphatidylserine from plasma
      membrane to endomembrane. Staurosporines are more active against K-Ras than H
      Ras. K-Ras is displaced to endosomes and undergoes proteasomal-independent
      degradation, whereas H-Ras redistributes to the Golgi and is not degraded. K-Ras
      nanoclustering on the plasma membrane is also inhibited. Ras mislocalization does
      not correlate with protein kinase C inhibition or induction of apoptosis.
      Staurosporines selectively abrogate K-Ras signaling and proliferation of K-Ras
      transformed cells. These results identify staurosporines as novel inhibitors of
      phosphatidylserine trafficking, yield new insights into the role of
      phosphatidylserine and electrostatics in Ras plasma membrane targeting, and
      validate a new target for anti-Ras therapeutics.

PMID- 23124206
TI  - Phosphatidylethanolamine biosynthesis in mitochondria: phosphatidylserine (PS)
      trafficking is independent of a PS decarboxylase and intermembrane space proteins
      UPS1P and UPS2P.
AB  - Phosphatidylethanolamine (PE) plays important roles for the structure and
      function of mitochondria and other intracellular organelles. In yeast, the
      majority of PE is produced from phosphatidylserine (PS) by a mitochondrion
      located PS decarboxylase, Psd1p. Because PS is synthesized in the endoplasmic
      reticulum (ER), PS is transported from the ER to mitochondria and converted to
      PE. After its synthesis, a portion of PE moves back to the ER. Two mitochondrial
      proteins located in the intermembrane space, Ups1p and Ups2p, have been shown to
      regulate PE metabolism by controlling the export of PE. It remains to be
      determined where PS is decarboxylated in mitochondria and whether decarboxylation
      is coupled to trafficking of PS. Here, using fluorescent PS as a substrate in an
      in vitro assay for Psd1p-dependent PE production in isolated mitochondria, we
      show that PS is transferred from the mitochondrial outer membrane to the inner
      membrane independently of Psd1p, Ups1p, and Ups2p and decarboxylated to PE by
      Psd1p in the inner membrane. Interestingly, Ups1p is required for the maintenance
      of Psd1p and therefore PE production. Restoration of Psd1p levels rescued PE
      production defects in ups1Delta mitochondria. Our data provide novel mechanistic
      insight into PE biogenesis in mitochondria.

PMID- 23124207
TI  - My life with bacteriophage phi29.
AB  - This article is a survey of my scientific work over 52 years. During my
      postdoctoral stay in Severo Ochoa's laboratory, I determined the direction of
      reading of the genetic message, and I discovered two proteins that I showed to be
      involved in the initiation of protein synthesis. The work I have done in Spain
      with bacteriophage phi29 for 45 years has been very rewarding. I can say that I
      was lucky because I did not expect that phi29 would give so many interesting
      results, but I worked hard, with a lot of dedication and enthusiasm, and I was
      there when the luck arrived. I would like to emphasize our work on the control of
      phi29 DNA transcription and, in particular, the finding for the first time of a
      protein covalently linked to the 5'-ends of phi29 DNA that we later showed to be
      the primer for the initiation of phage DNA replication. Very relevant was the
      discovery of the phi29 DNA polymerase, with its properties of extremely high
      processivity and strand displacement capacity, together with its high fidelity.
      The phi29 DNA polymerase has become an ideal enzyme for DNA amplification, both
      rolling-circle and whole-genome linear amplification. I am also very proud of the
      many brilliant students and collaborators with whom I have worked over the years
      and who have become excellent scientists. This Reflections article is not
      intended to be the end of my scientific career. I expect to work for many years
      to come.

PMID- 23124208
TI  - cAMP-responsive element modulator alpha (CREMalpha) contributes to decreased
      Notch-1 expression in T cells from patients with active systemic lupus
      erythematosus (SLE).
AB  - Notch signaling constitutes an evolutionarily conserved pathway that transduces
      signals between neighboring cells and determines major decisions in cell
      proliferation, survival, and differentiation. Notch signaling has been shown to
      play a pivotal role during T cell lineage determination. T lymphocytes from
      patients with systemic lupus erythematosus (SLE) display a severely altered
      phenotype with several molecular and functional aberrations, including defective
      capacities to up-regulate Notch-1 receptor expression upon T cell receptor
      activation. Here, we demonstrate that basal Notch-1 expression is decreased in T
      cells from active SLE patients at the mRNA and protein levels in various T cell
      subpopulations. Notch-1 transcript numbers inversely correlate with disease
      activity in SLE patients. We provide evidence that both enhanced histone H3
      methylation and CpG DNA methylation of the human Notch-1 promoter contribute to
      decreased Notch-1 expression in SLE T cells. Previous data from our group
      identified cAMP-responsive element modulator alpha (CREMalpha), which is up
      regulated in SLE T cells, as a key regulator of epigenetic patterns and gene
      transcription, e.g. that of IL2 and IL17 genes. In this study, we observed
      increased CREMalpha binding to the Notch-1 promoter, which eventually resulted in
      significantly reduced Notch-1 promoter activity and gene transcription. Notably,
      decreased Notch-1 levels were associated with elevated IL-17A levels. Our data
      suggest a role for Notch-1 in SLE immunopathogenesis, and for the first time, we
      present molecular mechanisms that mediate dysregulated Notch-1 expression in SLE
      T cells.

PMID- 23124210
TI  - Synthesis and cytotoxicity of novel ursolic acid derivatives containing an acyl
      piperazine moiety.
AB  - This study designed and synthesized a series of novel ursolic acid derivatives in
      an attempt to develop potent antitumor agents. Their structures were confirmed
      using MS, IR, (1)H NMR and (13)C NMR. The inhibitory activities of the title
      compounds against the MGC-803 (gastric cancer cell) and Bcap-37 (breast cancer
      cell) human cancer cell lines were evaluated using standard MTT assay in vitro.
      The pharmacological results showed that some of the compounds displayed moderate
      to high levels of antitumor activities against the tested cancer cell lines and
      that most exhibited more potent inhibitory activities compared with ursolic acid.
      The mechanism of compound 4b was preliminarily investigated by acridine
      orange/ethidium bromide staining, Hoechst 33258 staining, TUNEL assay and flow
      cytometry, which revealed that the compound can induce cell apoptosis in MGC-803
      cells.

PMID- 23124209
TI  - Detection of reaction intermediates during human cystathionine beta-synthase
      monitored turnover and H2S production.
AB  - Human cystathionine beta-synthase (CBS), a novel heme-containing pyridoxal 5'
      phosphate enzyme, catalyzes the condensation of homocysteine and serine or
      cysteine to produce cystathionine and H(2)O or H(2)S, respectively. The presence
      of heme in CBS has limited spectrophotometric characterization of reaction
      intermediates by masking the absorption of the pyridoxal 5'-phosphate cofactor.
      In this study, we employed difference stopped-flow spectroscopy to characterize
      reaction intermediates formed under catalytic turnover conditions. The reactions
      of L-serine and L-cysteine with CBS resulted in the formation of a common
      aminoacrylate intermediate (k(obs) = 0.96 +/- 0.02 and 0.38 +/- 0.01 mM(-1) s(
      1), respectively, at 24  degrees C) with concomitant loss of H(2)O and H(2)S and
      without detectable accumulation of the external aldimine or other intermediates.
      Homocysteine reacted with the aminoacrylate intermediate with k(obs) = 40.6 +/-
      3.8 s(-1) and re-formed the internal aldimine. In the reverse direction, CBS
      reacted with cystathionine, forming the aminoacrylate intermediate with k(obs) =
      0.38 +/- 0.01 mM(-1) s(-1). This study provides the first insights into the pre
      steady-state kinetic mechanism of human CBS and indicates that the reaction is
      likely to be limited by a conformational change leading to product release.

PMID- 23124211
TI  - Synthesis and structure-activity relationship of potent, selective and orally
      active anthranilamide-based factor Xa inhibitors: application of weakly basic
      sulfoximine group as novel S4 binding element.
AB  - A novel series of potent and efficacious factor Xa inhibitors which possesses
      sulfoximine moiety as novel S4 binding element in anthranilamide chemotype has
      been identified. Lead optimization at this novel P4 group led to many potent
      factor Xa inhibitors with excellent anticoagulant activity in human plasma.
      Selected compounds were dosed orally in rats and checked for their ex vivo
      prothrombin time prolonging activity, which resulted in identification of
      compound 5-chloro-N-(5-chloropyridin-2-yl)-2-(4-(N-(2-(diethylamino)acetyl)-S
      methylsulfonimidoyl)benzamido)benzamide (18f). The detailed pharmacokinetic
      evaluation and subsequent metabolism study of 18f suggested the presence of an
      active metabolite. The compound 18f and its active metabolite 18b demonstrated
      excellent in vivo efficacy in both arterial and venous thrombosis model in rats
      and were found to be highly selective against related serine proteases. Based on
      this promising profile, compound 18f was selected for further evaluation.

PMID- 23124212
TI  - Synthesis of novel 1H-1,2,3-triazole tethered C-5 substituted uracil-isatin
      conjugates and their cytotoxic evaluation.
AB  - The present manuscript describes the synthesis of uracil-isatin hybrids via azide
      alkyne cycloadditions and their cytotoxic evaluation against three human cancer
      cell lines viz. HeLa (cervix), MCF-7 (breast) and DU145 (prostate) using MTT
      assay. The evaluation studies revealed the dependence of cytotoxicity on C-5
      substituents of both uracil and isatin as well as the alkyl chain length with
      compounds 6g and 6k showing IC(50) values 18.21 and 13.90 MUM respectively
      against DU145 cell lines. Most of the synthesized conjugates exhibited
      considerable selectivity against MCF-7 and DU145 cell lines.

PMID- 23124213
TI  - Novel 1,4-benzoxazine and 1,4-benzodioxine inhibitors of angiogenesis.
AB  - Esters of 1,4-benzoxazine and 1,4-benzodioxine compounds 1 and 10, which combine
      thrombin inhibitory and GPIIb/IIIa antagonistic activity in one molecule are
      shown to inhibit endothelial cell migration and tube formation in vitro and
      angiogenesis in the chicken chorioallantoic membrane (CAM) assay. The
      corresponding carboxylic acids 1 (R(2) = H) and 11 were devoid of anti-angiogenic
      activity, most probably due to their insufficient entry into the cell. Although
      thrombin inhibition remains the most probable explanation for their inhibition of
      angiogenesis, VEGFR2 kinase assay suggest that other targets such as VEGFR2 might
      be involved.

PMID- 23124214
TI  - Synthesis and biological evaluation of N-arylbenzo[b]thieno[3,2-d]pyrimidin-4
      amines and their pyrido and pyrazino analogues as Ser/Thr kinase inhibitors.
AB  - A useful and rapid access to libraries of N-arylbenzo[b]thieno[3,2-d]pyrimidin-4
      amines and their pyrido and pyrazino analogues was designed and optimized for the
      first time via microwave-accelerated condensation and Dimroth rearrangement of
      the starting anilines with N'-(2-cyanoaryl)-N,N-dimethylformimidamides obtained
      by reaction of thiophene precursors with dimethylformamide dimethylacetal. The
      inhibitory potency of the final products against five protein kinases (CDK5/p25,
      CK1delta/E, GSK3alpha/beta, DYRK1A and CLK1) was estimated. N
      arylpyrido[3',2':4,5]thieno[3,2-d]pyrimidin-4-amine series of compounds (4a-j)
      turned out to be particularly promising for the development of new
      pharmacological inhibitors of CK1 and CLK1 kinases.

PMID- 23124215
TI  - Affinity and activity profiling of unichiral 8-substituted 1,4-benzodioxane
      analogues of WB4101 reveals a potent and selective alpha1B-adrenoceptor
      antagonist.
AB  - Unichiral 8-substituted analogues of 2-[(2-(2,6
      dimethoxyphenoxy)ethyl)aminomethyl]-1,4-benzodioxane (WB4101) were synthesized
      and tested for binding affinity at cloned human alpha(1a)-, alpha(1b)-and
      alpha(1d)-adrenoreceptor (alpha(1a)-, alpha(1b)-and alpha(1d)-AR) and at native
      rat 5-HT(1A) receptor and for antagonist affinity at alpha(1A)-, alpha(1B)-and
      alpha(1D)-AR and at alpha(2A/D)-AR. Among the selected 8-substituents, namely
      fluorine, chlorine, methoxyl and hydroxyl, only the last caused significant
      decrease of alpha(1) binding affinity in comparison with the lead compound.
      Functional tests on the S isomers confirmed the detrimental effect of OH
      positioned in proximity to benzodioxane O(1). For the other three substituents
      (F, Cl, OMe), the alpha(1A) and the alpha(1D) antagonist affinities were
      generally lower than the alpha(1a) and alpha(1d) binding affinities, but not the
      alpha(1B) antagonist affinity, which was similar and sensibly higher compared to
      alpha(1b) binding affinity in the case of F and OMe respectively. This trend
      confers significant alpha(1B)-AR selectivity, in particular, to the 8-methoxy
      analogue of (S)-WB4101, a new potent (pA(2) 9.58) alpha(1B)-AR antagonist. The S
      enantiomers of all the tested compounds were proved to act as alpha(1)-AR inverse
      agonists in a vascular model.

PMID- 23124216
TI  - Novel peptidomimetic compounds containing redox active chalcogens and quinones as
      potential anticancer agents.
AB  - Many types of cancer cells are associated with a disturbed intracellular redox
      balance and oxidative stress (OS). Among the various agents employed to modulate
      the intracellular redox state of cells, certain redox catalysts containing
      quinone and chalcogen moieties have shown considerable promise. Passerini
      multicomponent reaction has been developed for the synthesis of agents combining
      two, three or even four redox centers in one molecule in a good yield. When
      incubated with cancer cells these agents inhibited cell proliferation and induced
      apoptotic cell death. Interestingly, some of these redox active compounds
      exhibited quite low toxicity with normal cells. The cause was obviously OS, which
      was reflected by significant decrease in reduced glutathione, subsequently cell
      cycle arrest and induction of apoptosis.

PMID- 23124217
TI  - Design, synthesis and evaluation of N-(substituted benzothiazol-2-yl)amides as
      anticonvulsant and neuroprotective.
AB  - A series of N-(substituted benzothiazol-2-yl)amide derivatives 2a-h and 4a-h were
      synthesized by the EDC coupling reactions of substituted-benzothiazol-2-amine
      with 4-oxo-4-phenylbutanoic acid/2-benzoyl benzoic acid and evaluated for their
      anticonvulsant and neuroprotective effect. N-(6-methoxybenzothiazol-2-yl)-4-oxo-4
      phenylbutanamide (2f) emerged as the most effective anticonvulsant with median
      doses of 40.96 mg/kg (MES ED(50)), 85.16 mg/kg (scPTZ ED(50)) and 347.6 mg/kg
      (TD(50)). Furthermore, compound 2f displayed promising neuroprotective effect by
      lowering the levels of MDA and LDH; therefore, it represents a potential lead in
      search for safer and effective anticonvulsants having neuroprotective effects.

PMID- 23124218
TI  - Synthesis, biological evaluation and chemometric analysis of indazole
      derivatives. 1,2-Disubstituted 5-nitroindazolinones, new prototypes of
      antichagasic drug.
AB  - Chagas disease chemotherapy, currently based on only two drugs, nifurtimox and
      benznidazole, is far from satisfactory and therefore the development of new
      antichagasic compounds remains an important goal. On the basis of antichagasic
      properties previously described for some 1,2-disubstituted 5-nitroindazolin-3
      ones (21, 33) and in order to initiate the optimization of activity of this kind
      of compounds, we have prepared a series of related analogs (22-32, 34-38, 58 and
      59) and tested in vitro these products against epimastigote forms of Trypanosoma
      cruzi. 2-Benzyl-1-propyl (22), 2-benzyl-1-isopropyl (23) and 2-benzyl-1-butyl
      (24) derivatives have shown high trypanocidal activity and low unspecific
      toxicity. Other indazole derivatives with different substitution patterns (1
      substituted 3-alkoxy-1H-indazoles and 2-substituted 3-alkoxy-2H-indazoles),
      arising from the synthetic procedures used to prepare the mentioned
      indazolinones, have moderate to low effectiveness. The exploration of SAR
      information using the concept of an activity landscape has been carried out with
      SARANEA software. We have also searched for structural similarities between 225
      known antiprotozoan drugs and compound 22. The results confirm that compounds 22
      24 constitute promising leads and that 5-nitroindazolin-3-one system is a novel
      anti-T. cruzi scaffold which may represent an important therapeutic alternative
      for the treatment of Chagas disease.

PMID- 23124219
TI  - Mechanism-based design, synthesis and biological studies of N5-substituted
      tetrahydrofolate analogs as inhibitors of cobalamin-dependent methionine synthase
      and potential anticancer agents.
AB  - A number of 8-deazatetrahydrofolates bearing electrophilic groups on N(5) were
      designed and synthesized based on the action mechanism of methionine synthase,
      and their biological activities were investigated as well. Compounds (11b, 12b
      and 16) showed the most active against methionine synthase (IC(50): 8.11 MUM,
      1.73 MUM, 1.43 MUM). In addition, the cytotoxicity to human tumor cell lines and
      dihydrofolate reductase (DHFR) inhibition by target compounds were evaluated.

PMID- 23124220
TI  - Novel drug carriers: from grafted polymers to cross-linked vesicles.
AB  - A simple and straightforward method of self-assembling grafted copolymers was
      developed to fabricate cross-linked polymer vesicles, which could conjugate
      anticancer drug cis-platinum and possess the capability of a high drug loading
      content, and a steady release rate.

PMID- 23124221
TI  - Association of the gene encoding stearoyl-CoA desaturase (SCD) with fatty acid
      composition in an intercross population between Landrace and Korean native pigs.
AB  - Fatty acid (FA) composition is one of the most important parameters for the
      evaluation of meat quality. The stearoyl-CoA desaturase (SCD) gene is considered
      a positional candidate gene affecting FA composition in SSC14, based on previous
      quantitative trait loci studies. To evaluate the association of the SCD gene with
      FA composition in a Korean native pig * Landrace F(2) intercross population, we
      genotyped six single nucleotide polymorphisms (SNPs) of the SCD gene located in
      promoter region [2 SNPs (g.-353T>C, g.-233T>C)], exonic region [1 SNP (g.817C>T)
      in exon 2] and 3' UTR [3 SNPs (g.13311C>G, g.14384G>A, and g.14424C>T)]
      identified by massively parallel sequencing technology. Eighteen FA composition
      traits were measured in more than the 950 F(2) animals. A mixed-effect model was
      used to evaluate associations between these SNPs and FA composition traits in the
      F(2) intercross population. A detailed investigation detected that the five FA
      composition traits [palmitoleic acid (C16:1), stearic acid (C18:0), arachidic
      acid (C20:0), saturated FA, and unsaturated FA] were highly significant (P < 4.7
      * 10(-5); C20:0) in association with the SNP g.-233T>C, SNP g.817C>T, SNP
      g.13311C>G and SNP g.14384G>A in the SCD gene, whereas SNP g.14424C>T was only
      significantly associated with palmitoleic acid (C16:1, P = 1.4 * 10(-3)). No
      significant association of FA composition traits with SNP g.-353T>C was detected.
      In particular, the SNP g.14384G>A accounted for 30.6 % of the additive genetic
      variance of palmitoleic acid (P = 1.9 * 10(-10)). These results suggest the SCD
      gene has a strong effect on FA composition in the crossbred pig population.

PMID- 23124222
TI  - A synthetic cadmium metallothionein gene (PMCd1syn) of Paramecium species:
      expression, purification and characteristics of metallothionein protein.
AB  - Metallothioneins (MTs) are metal binding proteins that are rich in cysteine
      residues constituting 10-30 % of the total protein, and in which the thiol groups
      bind to the metal ions. The increasing amount of metal ions in the medium have
      shown increased production of MTs by different organisms such as bacteria,
      protozoa and mammals like humans. PMCd1 is the first gene ever discovered in
      Paramecium, a ciliated protozoan, that could produce this MT in response to
      cadmium. In this study the PMCd1syn gene has been cloned in pET41a expression
      vector and expressed in an Escherichia coli BL21-codonplus strain for the first
      time. Since the gene PMCd1 amplified from Paramecium contained 10 codons, which
      could act as stop codons during expression in E. coli, this gene of 612 bps was
      synthesized to substitute these (stop) codons for the Paramecium sp. specific
      amino acids. For stability of the expressed protein, glutathione-S-transferase
      gene was fused with PMCd1syn gene and coexpressed. The cells expressing PMCd1syn
      demonstrated increased accumulation of cadmium. This is the first report of
      cadmium MT protein expressed from Paramecium species, particularly from synthetic
      MT gene (PMCd1syn). This fusion protein, the molecular weight of which has been
      confirmed to be 53.03 kDa with MALDI analysis, is rich in cysteine residues, and
      has been shown for the first time in this ciliate to bind to and sequester Cd(2+)
      ions.

PMID- 23124223
TI  - Increased expression levels of vitronectin in the maternal-fetal interface of
      placenta in early-onset severe preeclampsia.
AB  - Preeclampsia (PE) is a pregnancy-specific disease, the pathogenesis of which
      remains unclear. The present study was designed to analyze whether vitronectin
      (VN), a multifunctional human glycoprotein, is expressed in PE and normal
      placentas. Furthermore, we aimed to explore VN expression profiles in relation to
      the pathogenesis of PE. Placental samples and plasma of early-onset severe PE
      (EOSP), late-onset severe PE (LOSP) and 2 control groups corresponding to EOSP
      and LOSP were collected. Immunohistochemistry, immunofluorescence and western
      blot analysis were used to detect VN protein expression profiles. mRNA expression
      levels of VN were detected by reverse transcription polymerase chain reaction (RT
      PCR). The impact of VN on coagulation was investigated by comparing differences
      in coagulation parameters. Our results demonstrate that expression levels of VN
      in the maternal-fetal interface of the EOSP group are the highest (P<0.001). The
      expression levels of VN in descending order in infarct center, infarct edge, near
      infarct tissues and away from infarct tissues were identified (P<0.001).
      Immunofluorescence and immunoblotting were consistent with immunohistochemical
      results. The VN mRNA expression was detected. Prothrombin time (PT) was
      significantly shorter in EOSP compared with the control group (P<0.05), which had
      a significant negative correlation with expression levels of VN in the placental
      tissue of the group. VN may play a key role in repairing the lesions and limiting
      necrotic components into maternal blood through its adhesion. VN may be involved
      in the pathogenesis of EOSP by inducing an imbalance between coagulation and
      fibrinolysis. 

PMID- 23124224
TI  - Engineering signal peptides for enhanced protein secretion from Lactococcus
      lactis.
AB  - Lactococcus lactis is an attractive vehicle for biotechnological production of
      proteins and clinical delivery of therapeutics. In many such applications using
      this host, it is desirable to maximize secretion of recombinant proteins into the
      extracellular space, which is typically achieved by using the native signal
      peptide from a major secreted lactococcal protein, Usp45. In order to further
      increase protein secretion from L. lactis, inherent limitations of the Usp45
      signal peptide (Usp45sp) must be elucidated. Here, we performed extensive
      mutagenesis on Usp45sp to probe the effects of both the mRNA sequence (silent
      mutations) and the peptide sequence (amino acid substitutions) on secretion. We
      screened signal peptides based on their resulting secretion levels of
      Staphylococcus aureus nuclease and further evaluated them for secretion of
      Bacillus subtilis alpha-amylase. Silent mutations alone gave an increase of up to
      16% in the secretion of alpha-amylase through a mechanism consistent with relaxed
      mRNA folding around the ribosome binding site and enhanced translation. Targeted
      amino acid mutagenesis in Usp45sp, combined with additional silent mutations from
      the best clone in the initial screen, yielded an increase of up to 51% in maximum
      secretion of alpha-amylase while maintaining secretion at lower induction levels.
      The best sequence from our screen preserves the tripartite structure of the
      native signal peptide but increases the positive charge of the n-region. Our
      study presents the first example of an engineered L. lactis signal peptide with a
      higher secretion yield than Usp45sp and, more generally, provides strategies for
      further enhancing protein secretion in bacterial hosts.

PMID- 23124225
TI  - Occurrence of virulence genes associated with Diarrheagenic pathotypes in
      Escherichia coli isolates from surface water.
AB  - Escherichia coli isolates (n = 300) collected from six sites in subtropical
      Brisbane, Australia, prior to and after storm events were tested for the presence
      of 11 virulence genes (VGs) specific to diarrheagenic pathotypes. The presence of
      eaeA, stx(1), stx(2), and ehxA genes specific for the enterohemorrhagic E. coli
      (EHEC) pathotype was detected in 56%, 6%, 10%, and 13% of isolates, respectively.
      The VGs astA (69%) and aggR (29%), carried by enteroaggregative (EAEC)
      pathotypes, were frequently detected in E. coli isolates. The enteropathogenic E.
      coli (EPEC) gene bfp was detected in 24% of isolates. In addition, enteroinvasive
      E. coli (EIEC) VG ipaH was also detected in 14% of isolates. During dry periods,
      isolates belonging to the EAEC pathotype were most commonly detected (23%),
      followed by EHEC (11%) and EPEC (11%). Conversely, a more uniform prevalence of
      pathotypes, EPEC (14%), EAEC (12%), EIEC (10%), EHEC (7%), and ETEC (7%), was
      observed after the storm events. The results of this study highlight the
      widespread occurrence of potentially diarrheagenic pathotypes in the urban
      aquatic ecosystems. While the presence of VGs in E. coli isolates alone is
      insufficient to determine pathogenicity, the presence of diarrheagenic E. coli
      pathotypes in high frequency after the storm events could lead to increased
      health risks if untreated storm water were to be used for nonpotable purposes and
      recreational activities.

PMID- 23124226
TI  - Comparing metabolic functionalities, community structures, and dynamics of
      herbicide-degrading communities cultivated with different substrate
      concentrations.
AB  - Two 4-chloro-2-methylphenoxyacetic acid (MCPA)-degrading enrichment cultures
      selected from an aquifer on low (0.1 mg liter(-1)) or high (25 mg liter(-1)) MCPA
      concentrations were compared in terms of metabolic activity, community
      composition, population growth, and single cell physiology. Different community
      compositions and major shifts in community structure following exposure to
      different MCPA concentrations were observed using both 16S rRNA gene denaturing
      gradient gel electrophoresis fingerprinting and pyrosequencing. The communities
      also differed in their MCPA-mineralizing activities. The enrichments selected on
      low concentrations mineralized MCPA with shorter lag phases than those selected
      on high concentrations. Flow cytometry measurements revealed that mineralization
      led to cell growth. The presence of low-nucleic acid-content bacteria (LNA
      bacteria) was correlated with mineralization activity in cultures selected on low
      herbicide concentrations. This suggests that LNA bacteria may play a role in
      degradation of low herbicide concentrations in aquifers impacted by agriculture.
      This study shows that subpopulations of herbicide-degrading bacteria that are
      adapted to different pesticide concentrations can coexist in the same environment
      and that using a low herbicide concentration enables enrichment of apparently
      oligotrophic subpopulations.

PMID- 23124227
TI  - Elimination of manganese(II,III) oxidation in Pseudomonas putida GB-1 by a double
      knockout of two putative multicopper oxidase genes.
AB  - Bacterial manganese(II) oxidation impacts the redox cycling of Mn, other
      elements, and compounds in the environment; therefore, it is important to
      understand the mechanisms of and enzymes responsible for Mn(II) oxidation. In
      several Mn(II)-oxidizing organisms, the identified Mn(II) oxidase belongs to
      either the multicopper oxidase (MCO) or the heme peroxidase family of proteins.
      However, the identity of the oxidase in Pseudomonas putida GB-1 has long remained
      unknown. To identify the P. putida GB-1 oxidase, we searched its genome and found
      several homologues of known or suspected Mn(II) oxidase-encoding genes (mnxG,
      mofA, moxA, and mopA). To narrow this list, we assumed that the Mn(II) oxidase
      gene would be conserved among Mn(II)-oxidizing pseudomonads but not in
      nonoxidizers and performed a genome comparison to 11 Pseudomonas species. We
      further assumed that the oxidase gene would be regulated by MnxR, a transcription
      factor required for Mn(II) oxidation. Two loci met all these criteria:
      PputGB1_2447, which encodes an MCO homologous to MnxG, and PputGB1_2665, which
      encodes an MCO with very low homology to MofA. In-frame deletions of each locus
      resulted in strains that retained some ability to oxidize Mn(II) or Mn(III); loss
      of oxidation was attained only upon deletion of both genes. These results suggest
      that PputGB1_2447 and PputGB1_2665 encode two MCOs that are independently capable
      of oxidizing both Mn(II) and Mn(III). The purpose of this redundancy is unclear;
      however, differences in oxidation phenotype for the single mutants suggest
      specialization in function for the two enzymes.

PMID- 23124228
TI  - Bacillus thuringiensis metalloproteinase Bmp1 functions as a nematicidal
      virulence factor.
AB  - Some Bacillus thuringiensis strains have high toxicity to nematodes. Nematicidal
      activity has been found in several families of crystal proteins, such as Cry5,
      Cry6, and Cry55. The B. thuringiensis strain YBT-1518 has three cry genes that
      have high nematicidal activity. The whole genome sequence of this strain contains
      multiple potential virulence factors. To evaluate the pathogenic potential of
      virulence factors, we focused on a metalloproteinase called Bmp1. It encompasses
      a consecutive N-terminal signal peptide, an FTP superfamily domain, an M4 neutral
      protease GluZincin superfamily, two Big-3 superfamily motifs, and a Gram-positive
      anchor superfamily motif as a C-terminal domain. Here, we showed that purified
      Bmp1 protein showed metalloproteinase activity and toxicity against
      Caenorhabditis elegans (the 50% lethal concentration is 610 +/- 9.37 MUg/ml). In
      addition, mixing Cry5Ba with Bmp1 protein enhanced the toxicity 7.9-fold (the
      expected toxicity of the two proteins calculated from their separate toxicities)
      against C. elegans. Confocal microscopic observation revealed that Bmp1 protein
      was detected from around the mouth and esophagus to the intestine. Striking
      microscopic images revealed that Bmp1 degrades intestine tissues, and the Cry5Ba
      causes intestinal shrinkage from the body wall. Thus, the B. thuringiensis Bmp1
      metalloproteinase is a nematicidal virulence factor. These findings give a new
      insight into the relationship between B. thuringiensis and its host nematodes.

PMID- 23124229
TI  - Chitin-induced gene expression in secondary metabolic pathways of Streptomyces
      coelicolor A3(2) grown in soil.
AB  - Microarray analyses revealed that the expression of genes for secondary
      metabolism together with that of primary metabolic genes was induced by chitin in
      autoclaved soil cultures of Streptomyces coelicolor A3(2). The data also
      indicated that DasR was involved in the regulation of gene expression for chitin
      catabolism, secondary metabolism, and stress responses.

PMID- 23124230
TI  - Quantification of yeast and bacterial gene transcripts in retail cheeses by
      reverse transcription-quantitative PCR.
AB  - The cheese microbiota contributes to a large extent to the development of the
      typical color, flavor, and texture of the final product. Its composition is not
      well defined in most cases and varies from one cheese to another. The aim of the
      present study was to establish procedures for gene transcript quantification in
      cheeses by reverse transcription-quantitative PCR. Total RNA was extracted from
      five smear-ripened cheeses purchased on the retail market, using a method that
      does not involve prior separation of microbial cells. 16S rRNA and malate:quinone
      oxidoreductase gene transcripts of Corynebacterium casei, Brevibacterium
      aurantiacum, and Arthrobacter arilaitensis and 26S rRNA and beta tubulin gene
      transcripts of Geotrichum candidum and Debaryomyces hansenii could be detected
      and quantified in most of the samples. Three types of normalization were applied:
      against total RNA, against the amount of cheese, and against a reference gene.
      For the first two types of normalization, differences of reverse transcription
      efficiencies from one sample to another were taken into account by analysis of
      exogenous control mRNA. No good correlation was found between the abundances of
      target mRNA or rRNA transcripts and the viable cell concentration of the
      corresponding species. However, in most cases, no mRNA transcripts were detected
      for species that did not belong to the dominant species. The applications of gene
      expression measurement in cheeses containing an undefined microbiota, as well as
      issues concerning the strategy of normalization and the assessment of
      amplification specificity, are discussed.

PMID- 23124231
TI  - Construction of a broad-host-range Tn7-based vector for single-copy P(BAD)
      controlled gene expression in gram-negative bacteria.
AB  - We describe a mini-Tn7-based broad-host-range expression cassette for arabinose
      inducible gene expression from the P(BAD) promoter. This delivery vector, pTJ1,
      can integrate a single copy of a gene into the chromosome of Gram-negative
      bacteria for diverse genetic applications, of which several are discussed, using
      Pseudomonas aeruginosa as the model host.

PMID- 23124232
TI  - Cello-oligosaccharide oxidation reveals differences between two lytic
      polysaccharide monooxygenases (family GH61) from Podospora anserina.
AB  - The genome of the coprophilic ascomycete Podospora anserina encodes 33 different
      genes encoding copper-dependent lytic polysaccharide monooxygenases (LPMOs) from
      glycoside hydrolase family 61 (GH61). In this study, two of these enzymes (P.
      anserina GH61A [PaGH61A] and PaGH61B), which both harbored a family 1
      carbohydrate binding module, were successfully produced in Pichia pastoris.
      Synergistic cooperation between PaGH61A or PaGH61B with the cellobiose
      dehydrogenase (CDH) of Pycnoporus cinnabarinus on cellulose resulted in the
      formation of oxidized and nonoxidized cello-oligosaccharides. A striking
      difference between PaGH61A and PaGH61B was observed through the identification of
      the products, among which were doubly and triply oxidized cellodextrins, which
      were released only by the combination of PaGH61B with CDH. The mass spectrometry
      fragmentation patterns of these oxidized products could be consistent with
      oxidation at the C-6 position with a geminal diol group. The different properties
      of PaGH61A and PaGH61B and their effect on the interaction with CDH are discussed
      in regard to the proposed in vivo function of the CDH/GH61 enzyme system in
      oxidative cellulose hydrolysis.

PMID- 23124233
TI  - Poly-gamma-(D)-glutamic acid capsule interferes with lytic infection of Bacillus
      anthracis by B. anthracis-specific bacteriophages.
AB  - The poly-gamma-d-glutamic acid capsule of Bacillus anthracis is a barrier to
      infection by B. anthracis-specific bacteriophages. Capsule expression was found
      to completely inhibit lytic infection by gamma phage, an observation supported by
      the demonstration that this phage does not elaborate a hydrolase that would
      facilitate penetration through the protective capsule outer layer.

PMID- 23124234
TI  - Diet-induced alterations of host cholesterol metabolism are likely to affect the
      gut microbiota composition in hamsters.
AB  - The gastrointestinal microbiota affects the metabolism of the mammalian host and
      has consequences for health. However, the complexity of gut microbial communities
      and host metabolic pathways make functional connections difficult to unravel,
      especially in terms of causation. In this study, we have characterized the fecal
      microbiota of hamsters whose cholesterol metabolism was extensively modulated by
      the dietary addition of plant sterol esters (PSE). PSE intake induced dramatic
      shifts in the fecal microbiota, reducing several bacterial taxa within the
      families Coriobacteriaceae and Erysipelotrichaceae. The abundance of these taxa
      displayed remarkably high correlations with host cholesterol metabolites. Most
      importantly, the associations between several bacterial taxa with fecal and
      biliary cholesterol excretion showed an almost perfect fit to a sigmoidal
      nonlinear model of bacterial inhibition, suggesting that host cholesterol
      excretion can shape microbiota structure through the antibacterial action of
      cholesterol. In vitro experiments suggested a modest antibacterial effect of
      cholesterol, and especially of cholesteryl-linoleate, but not plant sterols when
      included in model bile micelles. The findings obtained in this study are relevant
      to our understanding of gut microbiota-host lipid metabolism interactions, as
      they provide the first evidence for a role of cholesterol excreted with the bile
      as a relevant host factor that modulates the gut microbiota. The findings further
      suggest that the connections between Coriobacteriaceae and Erysipelotrichaceae
      and host lipid metabolism, which have been observed in several studies, could be
      caused by a metabolic phenotype of the host (cholesterol excretion) affecting the
      gut microbiota.

PMID- 23124235
TI  - Intracellular free iron and its potential role in ultrahigh-pressure-induced
      inactivation of Escherichia coli.
AB  - Intracellular free iron of Escherichia coli was determined by whole-cell electron
      paramagnetic resonance spectrometry. Ultrahigh pressure (UHP) increased both
      intracellular free iron and cell lethality in a pressure-dose-dependent manner.
      The iron chelator 2,2'-dipyridyl protected cells against UHP treatments. A
      mutation that produced iron overload conditions sensitized E. coli to UHP
      treatment.

PMID- 23124236
TI  - Molecular control of sucrose utilization in Escherichia coli W, an efficient
      sucrose-utilizing strain.
AB  - Sucrose is an industrially important carbon source for microbial fermentation.
      Sucrose utilization in Escherichia coli, however, is poorly understood, and most
      industrial strains cannot utilize sucrose. The roles of the chromosomally encoded
      sucrose catabolism (csc) genes in E. coli W were examined by knockout and
      overexpression experiments. At low sucrose concentrations, the csc genes are
      repressed and cells cannot grow. Removal of either the repressor protein (cscR)
      or the fructokinase (cscK) gene facilitated derepression. Furthermore,
      combinatorial knockout of cscR and cscK conferred an improved growth rate on low
      sucrose. The invertase (cscA) and sucrose transporter (cscB) genes are essential
      for sucrose catabolism in E. coli W, demonstrating that no other genes can
      provide sucrose transport or inversion activities. However, cscK is not essential
      for sucrose utilization. Fructose is excreted into the medium by the cscK
      knockout strain in the presence of high sucrose, whereas at low sucrose (when
      carbon availability is limiting), fructose is utilized by the cell.
      Overexpression of cscA, cscAK, or cscAB could complement the WDeltacscRKAB
      knockout mutant or confer growth on a K-12 strain which could not naturally
      utilize sucrose. However, phenotypic stability and relatively good growth rates
      were observed in the K-12 strain only when overexpressing cscAB, and full growth
      rate complementation in WDeltacscRKAB also required cscAB. Our understanding of
      sucrose utilization can be used to improve E. coli W and engineer sucrose
      utilization in strains which do not naturally utilize sucrose, allowing
      substitution of sucrose for other, less desirable carbon sources in industrial
      fermentations.

PMID- 23124237
TI  - Gene flow, recombination, and selection in cyanobacteria: population structure of
      geographically related Planktothrix freshwater strains.
AB  - Several Planktothrix strains, each producing a distinct oligopeptide profile,
      have been shown to coexist within Lake Steinsfjorden (Norway). Using nonribosomal
      peptide synthetase (NRPS) genes as markers, it has been shown that the
      Planktothrix community comprises distinct genetic variants displaying differences
      in bloom dynamics, suggesting a Planktothrix subpopulation structure. Here, we
      investigate the Planktothrix variants inhabiting four lakes in southeast of
      Norway utilizing both NRPS and non-NRPS genes. Phylogenetic analyses showed
      similar topologies for both NRPS and non-NRPS genes, and the lakes appear to have
      similar structuring of Planktothrix genetic variants. The structure of distinct
      variants was also supported by very low genetic diversity within variants
      compared to the between-variant diversity. Incongruent topologies and split
      decomposition revealed recombination events between Planktothrix variants. In
      several strains the gene variants seem to be a result of recombination. Both NRPS
      and non-NRPS genes are dominated by purifying selection; however, sites subjected
      to positive selection were also detected. The presence of similar and well
      separated Planktothrix variants with low internal genetic diversity indicates
      gene flow within Planktothrix populations. Further, the low genetic diversity
      found between lakes (similar range as within lakes) indicates gene flow also
      between Planktothrix populations and suggests recent, or recurrent, dispersals.
      Our data also indicate that recombination has resulted in new genetic variants.
      Stability within variants and the development of new variants are likely to be
      influenced by selection patterns and within-variant homologous recombination.

PMID- 23124238
TI  - Enhanced gene detection assays for fumarate-adding enzymes allow uncovering of
      anaerobic hydrocarbon degraders in terrestrial and marine systems.
AB  - The detection of anaerobic hydrocarbon degrader populations via catabolic gene
      markers is important for the understanding of processes at contaminated sites.
      Fumarate-adding enzymes (FAEs; i.e., benzylsuccinate and alkylsuccinate
      synthases) have already been established as specific functional marker genes for
      anaerobic hydrocarbon degraders. Several recent studies based on pure cultures
      and laboratory enrichments have shown the existence of new and deeply branching
      FAE gene lineages, such as clostridial benzylsuccinate synthases and homologues,
      as well as naphthylmethylsuccinate synthases. However, established FAE gene
      detection assays were not designed to target these novel lineages, and
      consequently, their detectability in different environments remains obscure.
      Here, we present a new suite of parallel primer sets for detecting the
      comprehensive range of FAE markers known to date, including clostridial
      benzylsuccinate, naphthylmethylsuccinate, and alkylsuccinate synthases. It was
      not possible to develop one single assay spanning the complete diversity of FAE
      genes alone. The enhanced assays were tested with a range of hydrocarbon
      degrading pure cultures, enrichments, and environmental samples of marine and
      terrestrial origin. They revealed the presence of several, partially unexpected
      FAE gene lineages not detected in these environments before: distinct
      deltaproteobacterial and also clostridial bssA homologues as well as
      environmental nmsA homologues. These findings were backed up by dual-digest
      terminal restriction fragment length polymorphism diagnostics to identify FAE
      gene populations independently of sequencing. This allows rapid insights into
      intrinsic degrader populations and degradation potentials established in aromatic
      and aliphatic hydrocarbon-impacted environmental systems.

PMID- 23124241
TI  - Spatiotemporal analysis of Cryptosporidium species/genotypes and relationships
      with other zoonotic pathogens in surface water from mixed-use watersheds.
AB  - Nearly 690 raw surface water samples were collected during a 6-year period from
      multiple watersheds in the South Nation River basin, Ontario, Canada.
      Cryptosporidium oocysts in water samples were enumerated, sequenced, and
      genotyped by detailed phylogenetic analysis. The resulting species and genotypes
      were assigned to broad, known host and human infection risk classes.
      Wildlife/unknown, livestock, avian, and human host classes occurred in 21, 13, 3,
      and <1% of sampled surface waters, respectively. Cryptosporidium andersoni was
      the most commonly detected livestock species, while muskrat I and II genotypes
      were the most dominant wildlife genotypes. The presence of Giardia spp.,
      Salmonella spp., Campylobacter spp., and Escherichia coli O157:H7 was evaluated
      in all water samples. The greatest significant odds ratios (odds of pathogen
      presence when host class is present/odds of pathogen presence when host class is
      absent) for Giardia spp., Campylobacter spp., and Salmonella spp. in water were
      associated, respectively, with livestock (odds ratio of 3.1), avian (4.3), and
      livestock (9.3) host classes. Classification and regression tree analyses (CART)
      were used to group generalized host and human infection risk classes on the basis
      of a broad range of environmental and land use variables while tracking
      cooccurrence of zoonotic pathogens in these groupings. The occurrence of
      livestock-associated Cryptosporidium was most strongly related to agricultural
      water pollution in the fall (conditions also associated with elevated odds ratios
      of other zoonotic pathogens occurring in water in relation to all sampling
      conditions), whereas wildlife/unknown sources of Cryptosporidium were
      geospatially associated with smaller watercourses where urban/rural development
      was relatively lower. Conditions that support wildlife may not necessarily
      increase overall human infection risks associated with Cryptosporidium since most
      Cryptosporidium genotypes classed as wildlife in this study (e.g., muskrat I and
      II genotype) do not pose significant infection risks to humans. Consequently,
      from a human health perspective, land use practices in agricultural watersheds
      that create opportunities for wildlife to flourish should not be rejected solely
      on the basis of their potential to increase relative proportions of wildlife
      fecal contamination in surface water. The present study suggests that mitigating
      livestock fecal pollution in surface water in this region would likely reduce
      human infection risks associated with Cryptosporidium and other zoonotic
      pathogens.

PMID- 23124240
TI  - Persistence and leaching potential of microorganisms and mineral N in animal
      manure applied to intact soil columns.
AB  - Pathogens may reach agricultural soils through application of animal manure and
      thereby pose a risk of contaminating crops as well as surface and groundwater.
      Treatment and handling of manure for improved nutrient and odor management may
      also influence the amount and fate of manure-borne pathogens in the soil. A study
      was conducted to investigate the leaching potentials of a phage (Salmonella
      enterica serovar Typhimurium bacteriophage 28B) and two bacteria, Escherichia
      coli and Enterococcus species, in a liquid fraction of raw pig slurry obtained by
      solid-liquid separation of this slurry and in this liquid fraction after
      ozonation, when applied to intact soil columns by subsurface injection. We also
      compared leaching potentials of surface-applied and subsurface-injected raw
      slurry. The columns were exposed to irrigation events (3.5-h period at 10 mm h(
      1)) after 1, 2, 3, and 4 weeks of incubation with collection of leachate. By the
      end of incubation, the distribution and survival of microorganisms in the soil of
      each treatment and in nonirrigated columns with injected raw slurry or liquid
      fraction were determined. E. coli in the leachates was quantified by both plate
      counts and quantitative PCR (qPCR) to assess the proportions of culturable and
      nonculturable (viable and nonviable) cells. Solid-liquid separation of slurry
      increased the redistribution in soil of contaminants in the liquid fraction
      compared to raw slurry, and the percent recovery of E. coli and Enterococcus
      species was higher for the liquid fraction than for raw slurry after the four
      leaching events. The liquid fraction also resulted in more leaching of all
      contaminants except Enterococcus species than did raw slurry. Ozonation reduced
      E. coli leaching only. Injection enhanced the leaching potential of the
      microorganisms investigated compared to surface application, probably because of
      a better survival with subsurface injection and a shorter leaching path.

PMID- 23124242
TI  - Regulons of three Pseudomonas syringae pv. tomato DC3000 iron starvation sigma
      factors.
AB  - Pseudomonas syringae pv. tomato DC3000 contains genes for 15 sigma factors. The
      majority are members of the extracytoplasmic function class of sigma factors,
      including five that belong to the iron starvation subgroup. In this study, we
      identified the genes controlled by three iron starvation sigma factors. Their
      regulons are composed of a small number of genes likely to be involved in iron
      uptake.

PMID- 23124239
TI  - Surveying the microbiome of ants: comparing 454 pyrosequencing with traditional
      methods to uncover bacterial diversity.
AB  - We are only beginning to understand the depth and breadth of microbial
      associations across the eukaryotic tree of life. Reliably assessing bacterial
      diversity is a key challenge, and next-generation sequencing approaches are
      facilitating this endeavor. In this study, we used 16S rRNA amplicon
      pyrosequencing to survey microbial diversity in ants. We compared 454 libraries
      with Sanger-sequenced clone libraries as well as cultivation of live bacteria.
      Pyrosequencing yielded 95,656 bacterial 16S rRNA reads from 19 samples derived
      from four colonies of one ant species. The most dominant bacterial orders in the
      microbiome of the turtle ant Cephalotes varians were Rhizobiales,
      Burkholderiales, Opitutales, Xanthomonadales, and Campylobacterales, as revealed
      through both 454 sequencing and cloning. Even after stringent quality filtering,
      pyrosequencing recovered 445 microbe operational taxonomic units (OTUs) not
      detected with traditional techniques. In comparing bacterial communities
      associated with specific tissues, we found that gut tissues had significantly
      higher diversity than nongut tissues, and many of the OTUs identified from these
      groups clustered within ant-specific lineages, indicating a deep coevolutionary
      history of Cephalotes ants and their associated microbes. These lineages likely
      function as nutritional symbionts. One of four ant colonies investigated was
      infected with a Spiroplasma sp. (order Entomoplasmatales), a potential ant
      pathogen. Our work shows that the microbiome associated with Cephalotes varians
      is dominated by a few dozen bacterial lineages and that 454 sequencing is a cost
      efficient tool to screen ant symbiont diversity.

PMID- 23124243
TI  - Molecular characterization of human-pathogenic microsporidia and Cyclospora
      cayetanensis isolated from various water sources in Spain: a year-long
      longitudinal study.
AB  - Recent studies suggest the involvement of water in the epidemiology of Cyclospora
      cayetanensis and some microsporidia. A total of 223 samples from four drinking
      water treatment plants (DWTPs), seven wastewater treatment plants (WWTPs), and
      six locations of influence (LI) on four river basins from Madrid, Spain, were
      analyzed from spring 2008 to winter 2009. Microsporidia were detected in 49% of
      samples (109/223), Cyclospora spp. were detected in 9% (20/223), and both
      parasites were found in 5.4% (12/223) of samples. Human-pathogenic microsporidia
      were detected, including Enterocytozoon bieneusi (C, D, and D-like genotypes),
      Encephalitozoon intestinalis, Encephalitozoon cuniculi (genotypes I and III), and
      Anncaliia algerae. C. cayetanensis was identified in 17 of 20 samples. To our
      knowledge, this is the first study that shows a year-long longitudinal study of
      C. cayetanensis in drinking water treatment plants. Additionally, data about the
      presence and molecular characterization of the human-pathogenic microsporidia in
      drinking water, wastewater, and locations of influence during 1 year in Spain are
      shown. It is noteworthy that although the DWTPs and WWTPs studied meet European
      and national regulations on water sanitary quality, both parasites were found in
      water samples from these plants, supporting the idea that new and appropriate
      controls and regulations for drinking water, wastewater, and recreational waters
      should be proposed to avoid health risks from these pathogens.

PMID- 23124245
TI  - Changes in microRNA expression in rat lungs caused by sevoflurane anesthesia: a
      TaqMan(r) low-density array study.
AB  - Reportedly, a large number of microRNAs (miRNAs) play an important role in
      inflammatory lung diseases such as asthma, idiopathic pulmonary fibrosis (IPF),
      acute respiratory distress syndrome (ARDS), and pulmonary arterial hypertension
      (PAH). Sevoflurane is routinely used to various patients, and its safety has been
      confirmed by clinical outcomes; however, its effects to lungs at the miRNA level
      have not been elucidated. In our previous genomic studies, we showed that
      sevoflurane anesthesia affected the expression of many genes and mRNAs in rat
      lungs. In this study, we comprehensively investigated changes in miRNA expression
      caused by sevoflurane anesthesia (2.0% and 4.0%). Sevoflurane anesthesia resulted
      in apparent changes in miRNA expression in rat lungs, and the pattern of 2.0%
      sevoflurane-induced changes in miRNA expression was similar to that of 4.0%
      sevoflurane. Some of the differentially expressed miRNAs are known to be involved
      in asthma, IPF, and PAH. Especially, miR-146a, the most up-regulated miRNA, is
      known to attenuate the toxic effects associated with LPS stimulation. We showed,
      for the first time, dynamic changes in miRNA expression caused by sevoflurane
      anesthesia, and moreover, our results were important to understand the influence
      of sevoflurane anesthesia on any patients suffered from various lung diseases.

PMID- 23124244
TI  - Bifidobacterial succession and correlation networks in a large unselected cohort
      of mothers and their children.
AB  - Bifidobacteria are a major microbial component of infant gut microbiota, which is
      believed to promote health benefits for the host and stimulate maturation of the
      immune system. Despite their perceived importance, very little is known about the
      natural development of and possible correlations between bifidobacteria in human
      populations. To address this knowledge gap, we analyzed stool samples from a
      randomly selected healthy cohort of 87 infants and their mothers with >90% of
      vaginal delivery and nearly 100% breast-feeding at 4 months. Fecal material was
      sampled during pregnancy, at 3 and 10 days, at 4 months, and at 1 and 2 years
      after birth. Stool samples were predicted to be rich in the species
      Bifidobacterium adolescentis, B. bifidum, B. dentium, B. breve, and B. longum.
      Due to high variation, we did not identify a clear age-related structure at the
      individual level. Within the population as a whole, however, there were clear age
      related successions. Negative correlations between the B. longum group and B.
      adolescentis were detected in adults and in 1- and 2-year-old children, whereas
      negative correlations between B. longum and B. breve were characteristic for
      newborns and 4-month-old infants. The highly structured age-related development
      of and correlation networks between bifidobacterial species during the first 2
      years of life mirrors their different or competing nutritional requirements,
      which in turn may be associated with specific biological functions in the
      development of healthy gut.

PMID- 23124246
TI  - Impairment of hippocampal long-term potentiation and failure of learning in mice
      treated with d-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol.
AB  - Gangliosides (sialic acid-containing glycosphingolipids) play important roles in
      many physiological functions, including synaptic plasticity in the hippocampus,
      which has been suggested as the basal cellular process of learning and memory in
      the brain. In the present study, long-term potentiation (LTP) and long-term
      depression (LTD) in CA1 hippocampal neurons and learning behavior were examined
      in mice treated with (D)-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol
      ((D)-PDMP), an inhibitor of ganglioside biosynthesis. Mice treated with (D)-PDMP,
      but not those treated with (L)-PDMP, showed impairment of LTP induction in
      hippocampal CA1 neurons without any significant change in LTD formation and also
      showed a failure of learning in the 4-pellet taking test. These results indicate
      that de novo synthesis of gangliosides in the brain is involved in synaptic
      plasticity of LTP in mouse hippocampal CA1 neurons and plays important roles in
      learning and memory.

PMID- 23124247
TI  - Collagen peptides enhance hippocampal neurogenesis and reduce anxiety related
      behavior in mice.
AB  - The present study examined the effects of enzymatically hydrolyzed collagen
      peptides on the level of hippocampal neurogenesis and emotional behavior in adult
      mice. For this purpose, two kinds of enzymatically hydrolyzed collagen peptides,
      the lower or higher molecular weight peptides (LP: below 2,000, HP: about 30,000)
      were administered orally to C57BL/6 mice for 4 weeks. As a result, the density of
      proliferating cells in subgranular zone of hippocampus showed a 1.2-fold increase
      in LP mice as compared with HP mice. Additionally, LP mice spent less time in
      closed arms than HP mice in elevated plus maze test to examine anxiety-related
      behavior. These results suggest that oral administration of the lower molecular
      weight peptides derived from collagen enhanced the hippocampal neurogenesis and
      exerted emotional behavior in adult mice.

PMID- 23124248
TI  - Application of floating cells for improved harvest in human chondrocyte culture.
AB  - Cell culture medium, which must be discarded during medium change, may contain
      many cells that do not attach to culture plates. In the present study, we focused
      on these floating cells and attempted to determine their usefulness for cartilage
      regeneration. We counted the number of floating cells discarded during medium
      change and compared the proliferation and differentiation between floating cells
      and their adherent counterparts. Chondrocyte monolayer culture at a density of 5
      * 103 cells/cm(2) produced viable floating cells at a rate of 2.7-3.2 * 10(3)
      cells/cm(2) per primary culture. When only the floating cells from one dish were
      harvested and replated in another dish, the number of cells was 2.8 * 10(4)
      cells/cm(2) (approximately half confluency) on culture day 7. The number of cells
      was half of that obtained by culturing only adherent cells (5 * 10(4)
      cells/cm(2)). The floating and adherent cells showed similar proliferation and
      differentiation properties. The recovery of floating cells from the culture
      medium could provide an approximately 1.5-fold increase in cell number over
      conventional monolayer culture. Thus, the collection of floating cells may be
      regarded as a simple, easy, and reliable method to increase the cell harvest for
      chondrocytes.

PMID- 23124249
TI  - Am80 induces neuronal differentiation via increased tropomyosin-related kinase B
      expression in a human neuroblastoma SH-SY5Y cell line.
AB  - Am80, a synthetic retinoid, has been used in differentiation therapy for acute
      promyelocytic leukemia (APL). All-trans retinoic acid (ATRA) as one of natural
      retinoid has been also used to treat APL. ATRA treatment causes neuronal
      differentiation by inducing tropomyosin-related kinase B (TrkB) expression and
      increasing the sensitivity to brain-derived neurotrophic factor (BDNF), a TrkB
      ligand. In the present study, we investigated the effects of Am80 on neuronal
      differentiation, BDNF sensitivity and TrkB expression in human neuroblastoma SH
      SY5Y cells. Treatment with Am80 induced morphological differentiation of neurite
      outgrowth and increased the expression of GAP43 mRNA, a neuronal differentiation
      marker. Additionally, TrkB protein was also increased, and exogenous BDNF
      stimulation after treatment with Am80 induced greater neurite outgrowth than
      without BDNF treatment. These results suggest that Am80 induced neuronal
      differentiation by increasing TrkB expression and BDNF sensitivity.

PMID- 23124250
TI  - Volatiles emitted from the roots of Vetiveria zizanioides suppress the decline in
      attention during a visual display terminal task.
AB  - The perennial grass Vetiveria zizanioides (vetiver) is mainly cultivated for its
      fragrant essential oil. Although the components of the oil and their biological
      activities have been studied extensively, the effect of the volatiles emitted
      from the roots of V. zizanioides on humans has so far remained unexplored. We
      investigated the effects of volatile compounds emitted from the cut roots of V.
      zizanioides (1.0 g, low-dose conditions; 30 g, high-dose conditions) on
      individuals during a visual display terminal task. Participants who breathed the
      volatile compounds emitted under low-dose conditions showed faster reaction times
      and stimulation of sympathetic nerve activity as measured by electrocardiography.
      These effects were not observed under high-dose conditions. The total amounnt of
      volatiles emitted during the experiment was 0.25 MUg under low-dose conditions
      and 1.35 MUg under high-dose conditions. These findings indicate that volatile
      compounds emitted from the roots of V. zizanioides under low-dose conditions may
      have helped subjects to maintain performance in visual discrimination tasks while
      maintaining high sympathetic nerve system activity.

PMID- 23124251
TI  - Laminin-5gamma2 chain expression is associated with tumor cell invasiveness and
      prognosis of lung squamous cell carcinoma.
AB  - Our previous study showed that tumor budding is a significant indicator of a poor
      prognosis in lung squamous cell carcinoma patients. Tumor budding-positive
      (Bud(+)) cases of lung squamous cell carcinoma (SqCC) showed locally aggressive
      growth, and the positivity was a useful indicator of the lymph node status and
      prognosis. The present study focused on the clinicopathologic significance of
      laminin-5gamma2 chain expression for local aggressiveness in lung SqCC. Laminin
      5gamma2 chain immunohistochemical stains in tissue samples were divided into
      three distinct types: basement membrane (B type; laminin-5gamma2 present in
      basement membrane), cytoplasmic (C type; laminin- 5gamma2 present in
      intracellular matrix), and invasive front (F type; laminin-5gamma2 present in
      cytoplasm, and strongly in part of peripheral nest). The F type was more common
      in Bud(+) cases than tumor budding-negative (Bud(-)) cases; B and C types were
      less common in Bud(+) cases (P < 0.001). The F type was more closely associated
      with decreased overall survival than the B and C types (P < 0.001 for both).
      Univariate analysis showed that the F type could be used to predict tumor size,
      lymph node metastasis, lymphatic invasion, tumor infiltrative patterns, tumor
      budding, and laminin-5gamma2 chain staining. Multivariate analysis showed that
      laminin-5gamma2 chain staining and tumor budding could be used to predict patient
      mortality (P < 0.001 and P = 0.005, respectively). The overall survival rate
      after curative resection was lower in patients with the F/Bud(+) type than in
      those with B+C/Bud(-) and B+C/Bud(+) types (P < 0.001 for both, log-rank test),
      and also lower with the F/Bud(-) type than the B+C/Bud(-) type. On the other
      hand, there was no significant difference between the F/Bud(+) and F/Bud(-)
      types. In conclusion, both laminin- 5gamma2 chain staining and tumor budding are
      associated with tumor cell invasiveness and are independent predictors of
      mortality in lung SqCC patients.

PMID- 23124252
TI  - Involvement of Prx3, a Drosophila ortholog of the thiol-dependent peroxidase
      PRDX3, in age-dependent oxidative stress resistance.
AB  - Peroxiredoxins (Prxs) are a family of multifunctional antioxidant thioredoxin
      dependent peroxidases. We used Drosophila melanogaster to examine the function of
      Prx3, the Drosophila homolog of human PRDX3. The oxidative stress response in
      adult Drosophila is age-dependent. RNAiinduced Prx3 knockdown in adult flies did
      not change their phenotype in normal conditions, but they had a shorter survival
      than the Prx3(+) controls in the presence of H2O2. The expression levels of the
      Prx3 were reduced by aging. These results suggest that Prx3 plays an important
      role in the oxidative stress response and is involved in the age-dependent
      competence of the oxidative stress response.

PMID- 23124253
TI  - 22-NBD-cholesterol as a novel fluorescent substrate for cholesterol-converting
      oxidoreductases.
AB  - Docking simulations and experimental data indicate that 22-(N-(7-nitrobenz-2-oxa
      1,3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3beta-ol (22-NBD-cholesterol), a
      common fluorescent sterol analog, binds into active sites of bovine cytochrome
      P450scc and microbial cholesterol dehydrogenases (CHDHs) and then undergoes
      regiospecific oxidations by these enzymes. The P450scc-dependent system was
      established to realize N-dealkylation activity toward 22-NBD-cholesterol,
      resulting in 7-nitrobenz[c][1,2,5]oxadiazole-4-amine (NBD-NH(2)) formation as a
      dominant fluorescent product. Basing on LC-MS data of the probes derivatized with
      hydroxylamine or cholesterol oxidase, both pregnenolone and 20-formyl-pregn-5-en
      3beta-ol were deduced to be steroidal co-products of NBD-NH(2), indicating
      intricate character of the reaction. Products of CHDH-mediated conversions of 22
      NBD-cholesterol were defined as 3-oxo-4-en and 3-oxo-5-en derivatives of the
      steroid. Moreover, the 3-oxo-4-en derivative was also found to be formed after 22
      NBD-cholesterol incubation with pathogenic bacterium Pseudomonas aeruginosa,
      indicating a possible application of the reaction for a selective and sensitive
      detection of some microbes. The 3-keto-4-en derivative of 22-NBD-cholesterol may
      be also suitable as a new fluorescent probe for steroid hormone-binding enzymes
      or receptors.

PMID- 23124254
TI  - Blood glucose concentrations and breast cancer risk in women without diabetes: a
      meta-analysis.
AB  - PURPOSE: Some studies have suggested an increased risk of breast cancer
      associated with elevated fasting serum glucose in nondiabetic subjects. Given how
      common both breast cancer and impaired glucose tolerance are in our aging
      societies, this is an important issue for public health. METHODS: We performed a
      systematic review of prospective cohort studies that examined the association
      between elevated serum glucose levels in nondiabetic subjects (levels below 7.0
      mml/L) and the subsequent risk of breast cancer. We performed a systematic
      literature search and extracted relevant data in a standard way. We then computed
      summary relative risks (SRR) and 95 % confidence intervals using a random effects
      model applied on the risk of highest versus lowest quantile of serum glucose
      concentrations. RESULTS: Ten cohort studies were retrieved. The SRR for all
      studies was 1.11 (1.00-1.23), with no evidence of heterogeneity or publication
      bias. The SRR was not affected when the analysis was restricted to the 8 studies
      that reported results for fasting subjects (SRR = 1.11; 95 % CI 0.98-1.25). Three
      studies provided BMI-unadjusted and BMI-adjusted SRRs of 1.24 (95 % CI 0.60-2.56)
      and 1.20 (95 % CI 0.63-2.27), respectively. Similar magnitudes of associations
      were observed in sensitivity analyses, but statistical significance was lost.
      CONCLUSION: In nondiabetic subjects, the risk of breast cancer associated with
      fasting serum glucose levels seems to be small. Potential limitations to this
      meta-analysis include the fact that not all studies reported risks adjusted for
      adiposity and that serum glucose levels of comparison groups were variable across
      studies.

PMID- 23124255
TI  - Five-year reoperation rates, cervical total disc replacement versus fusion,
      results of a prospective randomized clinical trial.
AB  - STUDY DESIGN: Prospective randomized clinical trial. OBJECTIVE: Determine the
      reasons for, and rates of, secondary surgical intervention up to 5 years at both
      the index and adjacent levels in patients treated with cervical total disc
      replacement (TDR) or anterior cervical discectomy and fusion (ACDF). Patients
      undergoing TDR received ProDisc-C. SUMMARY OF BACKGROUND DATA: Several outcome
      based prospective, randomized clinical trials have shown cervical TDR to be
      equivalent, if not superior, to fusion. The ability of TDR to allow decompression
      while maintaining motion has led many to suggest that adjacent-level degeneration
      and reoperation rates may be decreased when compared with fusion. METHODS: A
      total of 209 patients were treated and randomized (TDR, n = 103; ACDF, n = 106)
      at 13 sites. A secondary surgical intervention at any level was considered a
      reoperation. RESULTS: At 5 years, patients who received ProDisc-C had
      statistically significant higher probability of no secondary surgery at the index
      and adjacent levels than patients who underwent ACDF (97.1% vs. 85.5%, P =
      0.0079). No reoperations in patients who received ProDisc-C were performed for
      implant breakages or device failures. For patients who underwent ACDF, the most
      common reason for reoperation at the index level was pseudarthrosis, and for
      patients who underwent both ACDF and TDR, the most common reason for adjacent
      level surgery was recurrent neck and/or arm pain. CONCLUSION: Five-year follow-up
      of a prospective randomized clinical trial revealed 5-fold difference in
      reoperation rates when comparing patients who underwent ACDF (14.5%) with
      patients who underwent TDR (2.9%). These findings suggest the durability of TDR
      and its potential to slow the rate of adjacent-level disease.

PMID- 23124257
TI  - Creating a sustainable health system.

PMID- 23124256
TI  - Pain intensity and patients' acceptance of surgical complication risks with
      lumbar fusion.
AB  - STUDY DESIGN: Cross-sectional study with prospective recruitment. OBJECTIVE: To
      determine the relationship of pain intensity (back and leg) on patients'
      acceptance of surgical complication risks when deciding whether or not to undergo
      lumbar spinal fusion. SUMMARY OF BACKGROUND DATA: To formulate informed decisions
      regarding lumbar fusion surgery, preoperative discussions should include a review
      of the risk of complications balanced with the likelihood of symptom relief. Pain
      intensity has the potential to influence a patient's decision to consent to
      lumbar fusion. We hypothesized that pain intensity is associated with a patient's
      acceptance of surgical complication risks. METHODS: Patients being seen for the
      first time by a spine surgeon for treatment of a nontraumatic or non-neoplastic
      spinal disorder completed a structured questionnaire. It posed 24 scenarios, each
      presenting a combination of risks of 3 complications (nerve damage, wound
      infection, and nonunion) and probabilities of symptom relief. For each scenario,
      the patient indicated whether he or she would or would not consent to a fusion
      for low back pain (LBP). The sum of the scenarios in which the patient responded
      that he or she would elect surgery was calculated to represent acceptance of
      surgical complication risks. A variety of other data were also recorded,
      including age, sex, education level, race, history of nonspinal surgery, duration
      of pain, and history of spinal injections. Data were analyzed using bivariate and
      multivariate regression analyses. RESULTS: The mean number of scenarios accepted
      by 118 enrolled subjects was 10.2 (median, 8; SD, 8.5; range, 0-24, or 42.5% of
      scenarios). In general, subjects were more likely to accept scenarios with lower
      risks and higher efficacy. Spearman rank correlation estimates demonstrated a
      moderate association between the LBP intensity and acceptance of surgical
      complication risks (r = 0.37, P = 0.0001) whereas leg pain intensity had a weak
      but positive correlation (r = 0.19, P = 0.04). In bivariate analyses, a history
      of spinal injections was strongly associated with patients' acceptance of
      surgical complication risks and willingness to proceed with surgery (54.5% of
      scenarios accepted for those who had a history of spinal injections vs. 27.6% for
      those with no history of spinal injections, P = 0.0001). White patients were more
      willing to accept surgery (45.9% of scenarios) than non-white patients (28.4%, P
      = 0.03). With the available numbers, age, sex, history of nonspinal surgery,
      education, and the duration of pain demonstrated no clear association with
      acceptance of surgical complication risks. Although education overall was not an
      influential factor, more educated males had greater risk tolerance than less
      educated males whereas more educated females had less risk tolerance than less
      educated females (P = 0.023). In multivariate analysis, LBP intensity remained a
      highly statistically significant correlate (P = 0.001) of the proportion of
      scenarios accepted, as did a history of spinal injections (P = 0.001) and being
      white (0.03). CONCLUSION: The current investigation indicates that the intensity
      of LBP is the most influential factor affecting a patient's decision to accept
      risk of complication and symptom persistence when considering lumbar fusion. This
      relationship has not been previously shown for any surgical procedure. These data
      could potentially change the manner in which patients are counseled to make
      informed choices about spinal surgery. With growing interest in adverse events
      and complications, these data could be important in establishing guidelines for
      patient-directed surgical decision making.

PMID- 23124258
TI  - Occipital-C2 transarticular fixation for occipitocervical instability associated
      with occipitalization of the atlas in patients with klippel-feil syndrome, using
      intraoperative 3-dimensional navigation system.
AB  - STUDY DESIGN: Retrospective case series. OBJECTIVE: The aim of this study was to
      describe the clinical outcomes of cervical reduction and occipital-C2
      transarticular (OCTA) fixation with an assistance of intraoperative 3-dimensional
      navigation system (ITNS) during the treatment of reducible occipitocervical
      instability (OCI) in patients with Klippel-Feil syndrome (KFS) with
      occipitalization of the atlas and fusion of C2-C3. SUMMARY OF BACKGROUND DATA:
      Patients with KFS have congenital fusions of at least 2 cervical segments and may
      gradually develop symptoms at the hypermobile articulations adjacent to the
      cervical synostosis. This is particularly common in patients with KFS with
      occipitalization of the atlas and C2-C3 fusion. These patients may be at risk for
      instability and neurological complications of the occipitocervical junction that
      require occipitocervical reconstruction and fusion. Numerous treatment techniques
      are available for this pathological condition. However, there has yet to be a
      study of reducible OCI, showing successful treatment with intraoperative
      reduction and posterior OCTA fixation using ITNS. METHODS: From 2006 to 2011, 9
      patients with KFS with reducible OCI attributed to occipitalization of the atlas
      and C2-C3 fusion were surgically treated. After a limited foramen magnum
      decompression, reduction of the OCI was conducted by intraoperative cervical
      traction and extension, followed by OCTA fixation using a direct posterior
      approach and with the assistance of ITNS. The follow-up period ranged from 6 to
      60 months (mean, 31 mo). RESULTS: Good decompression and bone fusion were
      achieved in all the patients. The clinical symptoms had improved for all
      patients. There were no intraoperative or postoperative complications.
      CONCLUSION: In patients with KFS with occipitalization of the atlas and C2-C3
      fusion, manual cervical traction in tandem with cervical extension, followed by
      posterior OCTA fixation and fusion provides a safe, effective treatment of OCI
      and ventral brainstem impingement. IFTN is a feasible tool for monitoring
      cervical reduction and OCTA screw insertion in patients with KFS with this
      pathological condition.

PMID- 23124259
TI  - Biomechanical analysis of vertebral derotation techniques for the surgical
      correction of thoracic scoliosis. A numerical study through case simulations and
      a sensitivity analysis.
AB  - STUDY DESIGN: Biomechanical analysis of vertebral derotation techniques for the
      surgical correction of thoracic scoliosis. OBJECTIVE: To model and analyze
      vertebral derotation maneuvers biomechanically to maximize the tridimensional
      correction of scoliosis and minimize the implant-vertebra forces. SUMMARY OF
      BACKGROUND DATA: Vertebral derotation techniques were recently developed to
      improve the correction of scoliotic deformities in the transverse plane. Those
      techniques consist in applying a combination of moments and forces using a
      vertebral derotation device, cohesively linked to the thoracic apical pedicle
      screws, to derotate the spine and the rib cage. However, many variations of the
      technique exist and the correction mechanisms are not fully understood to achieve
      an optimal correction of scoliosis. METHODS: A biomechanical model was developed
      to simulate the instrumentation surgery numerically of 4 Lenke type 1 patients
      with scoliosis, instrumented using a vertebral derotation device and vertebral
      derotation maneuvers as major correction technique. Then, for each case, 32
      additional instrumentation surgical procedures were simulated to better
      understand the biomechanics of the vertebral derotation technique, varying the
      implant type and density, the number of derotation levels, the vertebral
      derotation angle and the posteriorly oriented force applied during the maneuver.
      RESULTS: On average, among 32 additional simulations, there was an important
      variability of the resulting apical vertebral rotation (15 degrees ) and the mean
      resultant implant-vertebra force (205 N) but little variability for the main
      thoracic Cobb angle (6 degrees ) and the thoracic kyphosis (4 degrees ). The
      implant type, the implant density and the vertebral derotation angle were the
      parameters that most influenced the correction of scoliosis. The correction in
      the coronal and transverse planes was improved using monoaxial pedicle screw
      density of 2 and a bilateral vertebral derotation maneuver on 3 levels at the
      apex of the thoracic curve, with an extra 15 degrees  applied on the vertebral
      derotation device. When reducing the implant density by 50%, it was possible to
      reduce the mean implant-vertebra forces while keeping a good correction.
      CONCLUSION: Biomechanically, it is possible to significantly improve the
      correction of thoracic scoliotic deformities, particularly in the transverse
      plane, when using vertebral derotation maneuvers.

PMID- 23124260
TI  - Anabolic effects of Peniel 2000, a peptide that regulates TGF-beta1 signaling on
      intervertebral disc degeneration.
AB  - STUDY DESIGN: An in vitro study with bovine intervertebral disc (IVD) cells and
      an in vivo study with a rabbit disc degeneration model on the extracellular
      matrix metabolism by a biglycan-derived peptide (Peniel 2000; P2K). OBJECTIVE: To
      investigate the mechanism for P2K-induced increases in extracellular matrix and
      in vitro and in vivo effects of the peptide on IVD. SUMMARY OF BACKGROUND DATA:
      Transforming growth factor-beta (TGF-beta) has a functional versatility on the
      metabolism of IVD cells, suggesting that the regulation of TGF-beta signaling is
      important in IVD degeneration. P2K was explored by an in silico drug discovery
      strategy to regulate TGF-beta signaling. METHODS: The putative target of P2K was
      verified by Biacore 3000 analysis and affinity purification using biotin-P2K. A
      monolayer culture system of bovine IVD cells was used to demonstrate the
      mechanism underlying the anabolic effects of P2K. Smad signaling and
      extracellular matrix metabolism of the IVD cells were investigated by Western
      blot and reverse transcription-polymerase chain reaction, respectively. The in
      vivo effect of P2K on degenerated disc was investigated using a rabbit model of
      disc degeneration. In 14 New Zealand white rabbits, disc degeneration was induced
      by percutaneous annular punctures. After 4 weeks, 3 consecutive discs in the same
      animal were treated with 5% lactose or P2K per disc. Twelve weeks after the
      treatment, the regenerative activity in the disc was examined by radiography,
      magnetic resonance imaging, and biochemical and histological analyses. RESULTS:
      Direct binding of P2K to an active form of TGF-beta1 was shown. Type II collagen
      and aggrecan were increased in TGF-beta1/P2K-treated bovine IVD cells, compared
      with nontreated and TGF-beta1-treated cells.In in vivo analysis, a single
      injection of P2K increased the disc height (P < 0.001) on the radiographs and
      improved the magnetic resonance imaging grade (P < 0.05) compared with controls.
      Biochemical analysis, showed a significant increase in PG content because of P2K
      treatment (P < 0.05). Histological analysis using disc degeneration grades
      demonstrated improvement in P2K-treated discs (P <0.01). CONCLUSION: A novel
      peptide, P2K, regulating TGF-beta1 signaling had an anabolic effect on bovine IVD
      cells and rabbit degenerated discs. The results suggest that P2K has considerable
      potential as a treatment of degenerative disc disease.

PMID- 23124261
TI  - In vivo tracing of neural tracts in tiptoe walking Yoshimura mice by diffusion
      tensor tractography.
AB  - STUDY DESIGN: Basic imaging experiment. OBJECTIVE: To determine whether in vivo
      diffusion tensor tractography (DTT) can be used to evaluate the axonal disruption
      of the chronically compressed spinal cord in tiptoe walking Yoshimura (twy) mice.
      SUMMARY OF BACKGROUND DATA: In cervical ossification of the posterior
      longitudinal ligament, axonal disruption results in motor and sensory functional
      impairment. Twy mice develop spontaneous calcification in the cervical ligaments,
      which causes chronic compression of the spinal cord. DTT is emerging as a
      powerful tool for tracing axonal fibers in vivo. METHODS: Five twy mice were
      subjected to DTT at 6, 15, and 20 weeks of age. Magnetic resonance imaging was
      performed using a 7.0-Tesla magnet (Biospec 70/16; Billerica, MA) with a
      CryoProbe. Diffusion tensor images were analyzed using TrackVis (Massachusetts
      General Hospital, MA). Motor performance was evaluated by Rotarod treadmill test
      and Digigait analysis. Histological analysis was performed by hematoxylin-eosin
      staining and immunostaining for RT-97 and SMI-31. RESULTS: High resolution DTT of
      twy mice in vivo was successful. A lower number of RT-97- or SMI-31-positive
      fibers were associated with more severe spinal cord compression, which was
      determined by observing the ligamentous calcification at the C2-C3 level in each
      twy mouse. The severity of canal stenosis based on magnetic resonance images was
      strongly correlated with the axial area of the spinal cord. The tract fiber (TF)
      ratio (the number of TFs at the C2-C3 level/the number of TFs at the C0-C1 level)
      was strongly correlated with the RT-97/SMI-31-positive area and with motor
      function (rotarod latency, stride length). Furthermore, a two-part linear
      regression analysis showed that canal stenosis around 50% to 60% caused a sharp
      decrease in the TF ratio before the deterioration of motor function. CONCLUSION:
      We conclude that DTT could be useful for detecting the early changes associated
      with the compressed spinal cord in cervical ossification of the posterior
      longitudinal ligament.

PMID- 23124262
TI  - Significant change or loss of intraoperative monitoring data: a 25-year
      experience in 12,375 spinal surgeries.
AB  - STUDY DESIGN: Retrospective. OBJECTIVE: The purpose of this study was to report
      the spectrum of intraoperative events responsible for a loss or significant
      change in intraoperative monitoring (IOM) data. SUMMARY OF BACKGROUND DATA: The
      efficacy of spinal cord/nerve root monitoring is demonstrated in a large, single
      institution series of patients, involving all levels of the spinal column
      (occiput to sacrum) and all spinal surgical procedures. METHODS: Multimodality
      IOM included somatosensory-evoked potentials, descending neurogenic-evoked
      potentials, neurogenic motor-evoked potentials, and spontaneous and triggered
      electromyography. A total of 12,375 patients who underwent surgery for spinal
      pathology between January 1985 and December 2010 were reviewed. There were 59.3%
      female patients (7178) and 40.7% male patients (5197). Procedures by spinal level
      were as follows: cervical 29.7% (3671), thoracic/thoracolumbar 45.4% (5624), and
      lumbosacral 24.9% (3080). Age at the time of surgery was as follows: older than
      18 years, 72.7% (242/8993) and younger than 18 years, 27.3% (144/3382). A total
      of 77.8% (9633) patients underwent primary surgical procedures and 22.2% (2742)
      patients underwent revision surgical procedures. RESULTS: A total of 406
      instances of IOM data change/loss occurred in 386 of 12,375 (3.1%) patients.
      Causes for data degradation/loss included the following: instrumentation (n =
      131), positioning (n = 85), correction (n = 56), systemic (n = 49), unknown (n =
      24), and focal spinal cord compression (n = 15). Data loss/change was seen in
      revision (6.1%/167 patients) surgical procedures more commonly than in primary
      procedures (2.3%/219 patients; P < 0.0001). Data improvement was demonstrated by
      88.7% (n = 360) after intervention versus 11.3% (n = 46) with no improvement in
      IOM data. One patient with improved data after intervention versus 14 with no
      improvement despite intervention had a permanent neurological deficit (P <
      0.0001). CONCLUSION: IOM data identified 386 (3.1%) patients with
      loss/degradation of data in 12,375 spinal surgical procedures. Fortunately, in
      93.3% of patients, intervention led to data recovery and no neurological
      deficits. Reduction from a potential (worst-case scenario) 3.1% (386) of patients
      with significant change/loss of IOM data to a permanent neurological deficit rate
      of 0.12% (15) patients was achieved (P < 0.0001), thus confirming efficacy of
      IOM.

PMID- 23124263
TI  - Predictors for mortality in elderly patients with cervical spine injury: a
      systematic methodological review.
AB  - STUDY DESIGN: Systematic methodological review. OBJECTIVE: Identify predictors
      for cervical spine injury (CSI) mortality in elderly patients by reviewing the
      available literature. SUMMARY OF BACKGROUND DATA: The proportion of active
      elderly individuals in society is increasing. This population is at high risk for
      CSI mortality. The results of studies identifying predictors for CSI mortality in
      the elderly population are often inconclusive or even conflicting. Currently,
      there is no set of predictors that can adequately identify and describe CSI
      mortality risk for the elderly. Thus, we performed a systematic review to
      identify the predictors for mortality in elderly patients with CSI. METHODS: We
      performed searches in the MEDLINE, EMBASE, ScienceDirect, and OVID databases
      (articles published prior to May 2012) for noninterventional studies that
      evaluated predictors for CSI mortality in the elderly. Only those observational
      studies with eligible data were included. Study quality was assessed using a
      modified quality assessment tool that was designed previously for an
      observational study. Study outcomes were combined with study quality scores using
      a best-evidence synthesis model. RESULTS: Twenty-three observational studies
      involving 2325 patients were included. These studies were published between 1993
      and 2011. According to the quality assessment criteria, 8 studies were of high
      quality, 11 studies were of moderate quality, and 4 studies were of low quality.
      We identified 3 strong evidence predictors for CSI mortality, including pre
      existing comorbidities, spinal cord injury, and age. We also identified 3
      moderate evidence predictors, 7 limited evidence predictors and 1 conflicting
      evidence predictor. CONCLUSION: Although there is no conclusive evidence
      regarding the mortality of elderly patients with CSI, these data provide
      information that can help us to make recommendations and to counsel patients and
      their families. Special attention should be paid to the 3 strong predictors.
      Further studies will be required to validate these predictors.

PMID- 23124264
TI  - Incidence of second cervical vertebral fractures far surpassed the rate predicted
      by the changing age distribution and growth among elderly persons in the United
      States (2005-2008).
AB  - STUDY DESIGN: Nationwide epidemiological cohort study. OBJECTIVE: To characterize
      the incidence of second cervical vertebral (C2) fractures by age and geographical
      region among the elderly Medicare population and to elucidate if the rate changed
      in the years 2005 to 2008. SUMMARY OF BACKGROUND DATA: Recent publications
      hypothesized that the rate of cervical vertebral fractures may be increasing. To
      date, there are no published nationwide reports describing the incidence and
      demographics of these injuries in the elderly US population. METHODS: Incidence
      of C2 fracture in the years 2005 to 2008 was determined by querying PearlDiver
      Technologies, Inc. (Warsaw, IN), a commercially available database, using
      International Classification of Diseases code 805.02. Rates were calculated using
      the PearlDiver reported person-counts as the numerator and the Center for
      Medicare and Medicare Services midyear population file as the denominator, and
      reported per 10,000 person-years (10,000 p-y). The age and geographical
      distributions of fractures were examined. Variability in rates was analyzed using
      the mean, standard deviation, 95% confidence intervals, chi tests, and Pearson
      correlation coefficients. RESULTS: Although the elderly population increased by
      6% between 2005 and 2008, the annual incidence of C2 fracture rose by 21%, from
      1.58 to 1.91 per 10,000 p-y, trending upward in a straight-line function (r =
      0.999, P = 0.0006). The incidence of fracture varied between age groups; however,
      an increase was observed in all age groups. Persons aged 65 to 74 years (the
      youngest age group) experienced the lowest incidence (0.63 in 2005 to 0.71 in
      2008), and the rate of increase was the smallest among the age groups examined
      (13%). Persons aged 85 and older demonstrated the highest incidence (4.36-5.67)
      and the greatest increase (30%). CONCLUSION: From 2005 to 2008, the overall
      incidence of C2 fracture rose at a rate that was 3.5 times faster than the
      elderly population growth.

PMID- 23124265
TI  - Comparison of the EuroQOL-5D with the Oswestry Disability Index, back and leg
      pain scores in patients with degenerative lumbar spine pathology.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVE: To evaluate the response behavior
      of EuroQOL-5D (EQ-5D) compared with the Oswestry Disability Index (ODI), and back
      and leg pain scores. SUMMARY OF BACKGROUND DATA: Recent changes in policies have
      highlighted the need for demonstration of both quality and cost effectiveness. In
      an effort to meet these requirements, surgeons are collecting health-related
      quality of life and utility data. Unfortunately, the burden of extensive data
      collection on both physician and patient is considerable. The EQ-5D is a commonly
      used, easily administered, brief utility measure that can provide both clinical
      and utility data. The EQ-5D has not yet been validated in spine patients in
      comparison with established outcome measures. METHODS: EQ-5D, ODI, back and leg
      pain (0-10) scores were collected as part of standard clinical practice. Spearman
      rank correlations between the ODI, back and leg pain scores, and the EQ-5D were
      determined. A subanalysis to determine dimension-specific effects was done. Data
      were categorized by level of low back disability and level of back and leg pain.
      RESULTS: Data from 8385 patients (5046 females, 3339 males), mean age 52 (range,
      18-96) were analyzed. There was a strong correlation between EQ-5D and ODI (r = 
      0.776) and between EQ-5D and back pain (r = -0.648); and moderate correlation
      between EQ-5D and leg pain scores (r = -0.538). Increasing disability, as
      measured by ODI, lead to lower EQ-5D scores, with similar response behavior for
      both back and leg pain scores. All correlations were statistically significant at
      P < 0.0001. CONCLUSION: The EQ-5D correlated well with established spine outcome
      measures, including ODI, and back and leg pain scores. EQ-5D correlated best with
      ODI scores. Correlation with back pain was stronger than leg pain, but all
      correlations were relatively strong. The EQ-5D can serve spine surgeons as an
      effective measure of clinical outcome and health utility for economic analysis.

PMID- 23124266
TI  - Cyclic-RGD is as effective as rhBMP-2 in anterior interbody fusion of the sheep
      cervical spine.
AB  - STUDY DESIGN: Radiological and histological assessment of fusion status after
      anterior cervical discectomy and fusion (ACDF) procedure in a sheep spinal fusion
      model. OBJECTIVE: To evaluate the efficacy of cyclic arginine-glycine-aspartic
      (cRGD) in comparison with recombinant human bone morphogenetic protein-2 (rhBMP
      2) on a mineralized collagen matrix (MCM). SUMMARY OF BACKGROUND DATA: A previous
      evaluation of MCM alone in comparison with autologous bone graft alone was not
      able to show an advantage on spinal fusion. The cRGD peptide sequence plays a
      major role in mediating cell adhesion. Studies have demonstrated enhances
      osteoblasts adhesion resulting in increased periimplant bone formation after
      implantcoating with cRGD. rhBMP-2 has already proven its ability to enhance
      spinal fusion. To date, no comparative in vivo evaluation of cRGD and rhBMP-2 in
      combination with a MCM for spinal fusion has been performed. METHODS: Twenty-four
      sheep (N = 8/group) underwent C3-C4 fusion. Implants: group 1: titanium cage with
      MCM and rhBMP-2; group 2: titanium cage with MCM and cRGD; control group:
      titanium cage with MCM alone. After 12 weeks fusion sites were evaluated by
      computed tomography to assess fusion status, bone mineral density as well as bony
      callus volume. Furthermore, histomorphological and histomorphometrical analysis
      of the fusion sites were performed. RESULTS: In comparison with the control
      group, cRGD, and rhBMP-2 groups showed a higher fusion rate in radiographical
      findings and a higher degree of interbody fusion in histomorphometrical analysis
      (P < 0.05). There was no significant difference in radiographical and
      histological parameters between the rhBMP-2 and the cRGD group. Although rhBMP-2
      demonstrated ectopic prevertebral bone formations, this effect was less prominent
      in the cRGD group. CONCLUSION: In this animal model the combination of cRGD and a
      mineralized collagen matrix showed superior fusion results in comparison with the
      mineralized collagen alone. Further, cRGD was comparably effective to rhBMP-2 in
      promoting interbody fusion by demonstrating less ectopic bone formations.

PMID- 23124268
TI  - Mid- to long-term outcomes in adolescent idiopathic scoliosis after instrumented
      posterior spinal fusion: a meta-analysis.
AB  - STUDY DESIGN: Meta-analysis on mid- to long-term outcomes in adolescent
      idiopathic scoliosis after instrumented posterior spinal fusion. OBJECTIVE: To
      compare mid- to long-term outcomes and complications of the most commonly used
      instrumentation systems in adolescent idiopathic scoliosis. SUMMARY OF BACKGROUND
      DATA: A meta-analysis of mid- to long-term results of different methods of
      instrumentation, including the most currently used all-pedicle screw construct,
      is lacking. METHODS: A structured literature review was conducted for studies
      concerning management of patients with adolescent idiopathic scoliosis with
      instrumented posterior fusion. Pooled means, standard deviations, and sample
      sizes were either identified or calculated on the basis of the results of each
      study. RESULTS: Meta-analyses were performed on outcomes from 27 studies.
      Overall, 1613 patients who had been treated with Harrington rods, 361 patients
      who had undergone Cotrel-Dubousset instrumentation, and 298 patients who managed
      with all-pedicle screw constructs were reviewed. The mean follow-up was 14.9
      years. Cotrel-Dubousset and pedicle screw instrumentations achieved a
      significantly greater degree of correction of the thoracic curve than Harrington
      rods (40.3 degrees  vs. 14.7 degrees ; P < 0.001 and 21.9 degrees  vs. 14.7
      degrees ; P = 0.005, respectively). Cotrel-Dubousset technique achieved a
      significantly higher degree of correction than all-pedicle screw construct in
      both the thoracic (40.3 degrees  vs. 21.9 degrees , respectively; P < 0.001) and
      lumbar curves (37.2 degrees  vs. 16 degrees , respectively; P < 0.001).
      Similarly, Cotrel-Dubousset construct achieved a greater correction of both
      thoracic kyphosis (33.5 degrees  vs. 23 degrees , respectively; P < 0.001) and
      lumbar lordosis (46 degrees  vs. 50.7 degrees , respectively; P = 0.002) than
      pedicle screws. All-pedicle screw fixation was associated with the lower risk of
      pseudarthrosis, infection, neurological deficit, and reoperation. CONCLUSION:
      This study confirms the negative effect of Harrington rods on sagittal alignment.
      We further found that the degree of correction in the coronal and sagittal planes
      was higher after Cotrel-Dubousset instrumentation than all-pedicle screw
      fixation. All-pedicle screw constructs offered the lower risk of mid- to long
      term complications and revision surgery.

PMID- 23124269
TI  - Incidence and risk factors of the retropharyngeal carotid artery on cervical
      magnetic resonance imaging.
AB  - STUDY DESIGN: Retrospective cohort. OBJECTIVE: Define incidence of anomalous
      carotid vasculature and associated risk factors as pertains to the anterior
      approach. SUMMARY OF BACKGROUND DATA: The carotid artery system, including the
      common, internal, and external branches, is lateral to the foramen
      transversarium. If unrecognized, aberrancies in carotid vessel anatomy can lead
      to devastating complications. METHODS: A total of 1000 cervical magnetic
      resonance imagings were screened to localize the carotid artery respective to
      medial/lateral location of the vessel at each segment from C2-C3 to C6-C7
      bilaterally. Vessel location was classified in 3 zones: lateral to the vertebral
      foramen (type I) (normal); between the lateral foramen and uncoverterbral joint
      (type II); and medial to the uncovertebral joint (type III). Type III locations
      were compared with age-matched controls for assessment of cervical alignment via
      the Ishihara index, C2-C7 angle, and degree of spondylosis. RESULTS: A total of
      123 patients demonstrated carotid artery anomalies (type II and III) (12.3%).
      Twenty-six patients had type III aberrancy (2.6%). Patients with anomalies were
      significantly older and more likely to be female (60 vs. 51 yr of age, 74% vs.
      57% female, respectively, P < 0.05). The type III group average age was 66.1
      years and 88% were female. Aberrancies were more likely right-sided and at C3-C4
      or cranial. C2-C7 angle showed significantly greater kyphosis in patients with
      anomalies compared with controls (6.2 vs. 14.4, P = 0.03). The number of severely
      spondolytic segments was significantly greater in patients with Type III
      locations than controls (2.0 vs. 1.1 P < 0.05). CONCLUSION: Carotid arterial
      anomalies occurred in 12.3% of cases; severe aberrancy was present in 2.6% of
      patients. In elderly females with kyphotic alignment, a high index of suspicion
      must be raised for aberrancy. Preoperative assessment of the vasculature in the
      anterior neck may avoid catastrophic complications.

PMID- 23124270
TI  - Fabrication of three-dimensional ordered nanodot array structures by a thermal
      dewetting method.
AB  - A new fabrication method for three-dimensional nanodot arrays with low  cost and
      high throughput is developed in this paper. In this process, firstly a 2D nanodot
      array is fabricated by combination of top-down and bottom-up approaches. A
      nanoplastic forming technique is utilized as the top-down approach to fabricate a
      groove grid pattern on an Au layer deposited on a substrate, and self
      organization by thermal dewetting is employed as the bottom-up approach. On the
      first-layer nanodot array, SiO(2) is deposited as a spacer layer. Au is then
      deposited on the spacer layer and thermal dewetting is conducted to fabricate a
      second-layer nanodot array. The effective parameters influencing dot formation on
      the second layer, including Au layer thickness and SiO(2) layer thickness, are
      studied. It is demonstrated that a 3D nanodot array of good vertical alignment is
      obtained by repeating the SiO(2) deposition, Au deposition and thermal dewetting.
      The mechanism of the dot agglomeration process is studied based on geometrical
      models. The effects of the spacer layer thickness and Au layer thickness on the
      morphology and alignment of the second-layer dots are discussed.

PMID- 23124272
TI  - Shoaling behaviour enhances risk of predation from multiple predator guilds in a
      marine fish.
AB  - Predicting the consequences of predator biodiversity loss on prey requires an
      understanding of multiple predator interactions. Predators are often assumed to
      have independent and additive effects on shared prey survival; however, multiple
      predator effects can be non-additive if predators foraging together reduce prey
      survival (risk enhancement) or increase prey survival through interference (risk
      reduction). In marine communities, juvenile reef fish experience very high
      mortality from two predator guilds with very different hunting modes and foraging
      domains-benthic and pelagic predator guilds. The few previous predator
      manipulation studies have found or assumed that mortality is independent and
      additive. We tested whether interacting predator guilds result in non-additive
      prey mortality and whether the detection of such effects change over time as prey
      are depleted. To do so, we examined the roles of benthic and pelagic predators on
      the survival of a juvenile shoaling zooplanktivorous temperate reef fish,
      Trachinops caudimaculatus, on artificial patch reefs over 2 months in Port
      Phillip Bay, Australia. We observed risk enhancement in the first 7 days, as
      shoaling behaviour placed prey between predator foraging domains with no
      effective refuge. At day 14 we observed additive mortality, and risk enhancement
      was no longer detectable. By days 28 and 62, pelagic predators were no longer
      significant sources of mortality and additivity was trivial. We hypothesize that
      declines in prey density led to reduced shoaling behaviour that brought prey more
      often into the domain of benthic predators, resulting in limited mortality from
      pelagic predators. Furthermore, pelagic predators may have spent less time
      patrolling reefs in response to declines in prey numbers. Our observation of the
      changing interaction between predators and prey has important implications for
      assessing the role of predation in regulating populations in complex communities.

PMID- 23124271
TI  - mTOR signaling in neural stem cells: from basic biology to disease.
AB  - The mammalian target of rapamycin (mTOR) pathway is a central controller of
      growth and homeostasis, and, as such, is implicated in disease states where
      growth is deregulated, namely cancer, metabolic diseases, and hamartoma syndromes
      like tuberous sclerosis complex (TSC). Accordingly, mTOR is also a pivotal
      regulator of the homeostasis of several distinct stem cell pools in which it
      finely tunes the balance between stem cell self-renewal and differentiation. mTOR
      hyperactivation in neural stem cells (NSCs) has been etiologically linked to the
      development of TSC-associated neurological lesions, such as brain hamartomas and
      benign tumors. Animal models generated by deletion of mTOR upstream regulators in
      different types of NSCs reproduce faithfully some of the TSC neurological
      alterations. Thus, mTOR dysregulation in NSCs seems to be responsible for the
      derangement of their homeostasis, thus leading to TSC development. Here we review
      recent advances in the molecular dissection of the mTOR cascade, its involvement
      in the maintenance of stem cell compartments, and in particular the implications
      of mTOR hyperactivation in NSCs in vivo and in vitro. 

PMID- 23124273
TI  - Evolutionary determinants of population differences in population growth rate *
      habitat temperature interactions in Chironomus riparius.
AB  - Little is known about intraspecific variation in fitness performance in response
      to thermal stress among natural populations and how this relates to evolutionary
      aspects of species ecology. In this study, population growth rate (PGR; a
      composite fitness measure) varied among five natural Chironomus riparius
      populations sampled across a climatic gradient when subjected to three
      temperature treatments reflecting the typical range of summer habitat
      temperatures (20, 24 and 28  degrees C). The variation could be explained by a
      complex model including effects of genetic drift, genetic diversity and
      adaptation to average temperature during the warmest month, in addition to
      experimental temperature. All populations suffered a decrease in PGR from 20 to
      28  degrees C and DeltaPGR was significantly correlated with the respective
      average habitat temperature in the warmest month-populations from warmer areas
      showing lower DeltaPGR. This implies that long-term exposure to higher
      temperatures in the warmest month (the key reproductive period for C. riparius)
      is likely to be a key selective force influencing fitness at higher temperatures.
      A comparison of phenotypic divergence and neutral genetic differentiation
      revealed that one phenotypic trait--the number of fertile egg masses per female-
      appeared to be under positive selection in some populations. Our findings support
      a role for response to temperature selection along a climatic gradient and
      suggest population history is a key determinant of intraspecific fitness
      variation. We stress the importance of integrating different types of data
      (climatic, experimental, genetic) in order to understand the effects of global
      climate change on biodiversity.

PMID- 23124274
TI  - Inaugural severe vaso-occlusive retinopathy in systemic lupus erythematosus.
AB  - Purpose To report the case of a patient with an inaugural severe bilateral vaso
      occlusive retinopathy due to systemic lupus erythematosus. Method Clinical
      examination, fundus pictures and fluorescein angiography were performed. Results
      A 26-year-old, healthy, African man presented with a meningo-encephalitic
      syndrome and a severe bilateral visual impairment. The fundus examination
      revealed multiple retinal vascular occlusions, and a fluorescein angiography
      showed retinal and choroidal ischemia bilaterally. In addition, based on the
      neurologic disorders, a pleuritis, a renal disorder and a hematologic disorder,
      systemic lupus erythematosus, was diagnosed. Conclusions Severe vaso-occlusive
      retinopathy in a 26-year-old man resulting in a significant visual loss as the
      initial manifestation of systemic lupus erythematosus. Central nervous system
      involvement during lupus might be more frequent in patients when serious retinal
      changes occur.

PMID- 23124276
TI  - Global exponential estimates of delayed stochastic neural networks with Markovian
      switching.
AB  - This paper is concerned with the global exponential estimating problem of delayed
      stochastic neural networks with Markovian switching. By fully taking the inherent
      characteristic of such kinds of neural networks into account, a novel stochastic
      Lyapunov functional is constructed in which as many as possible of the positive
      definite matrices are dependent on the system mode and a triple-integral term is
      introduced. Based on it, a delay- and mode-dependent criterion is derived under
      which not only the neural network is mean square exponentially stable but also
      the decay rate is well obtained. Moreover, it is shown that the established
      stability condition includes some existing ones as its special cases, and is thus
      less conservative. This approach is then extended to two more general cases where
      mode-dependent time-varying delays and parameter uncertainties are considered.
      Finally, three numerical examples are presented to demonstrate the performance
      and effectiveness of the developed approach.

PMID- 23124275
TI  - Therapist self-report of evidence-based practices in usual care for adolescent
      behavior problems: factor and construct validity.
AB  - This study introduces a therapist-report measure of evidence-based practices for
      adolescent conduct and substance use problems. The Inventory of Therapy
      Techniques-Adolescent Behavior Problems (ITT-ABP) is a post-session measure of 27
      techniques representing four approaches: cognitive-behavioral therapy (CBT),
      family therapy (FT), motivational interviewing (MI), and drug counseling (DC). A
      total of 822 protocols were collected from 32 therapists treating 71 adolescents
      in six usual care sites. Factor analyses identified three clinically coherent
      scales with strong internal consistency across the full sample: FT (8 items;
      alpha = .79), MI/CBT (8 items; alpha = .87), and DC (9 items, alpha = .90). The
      scales discriminated between therapists working in a family-oriented site versus
      other sites and showed moderate convergent validity with therapist reports of
      allegiance and skill in each approach. The ITT-ABP holds promise as a cost
      efficient quality assurance tool for supporting high-fidelity delivery of
      evidence-based practices in usual care. 

PMID- 23124277
TI  - A missense polymorphism (rs11466653, Met326Thr) of toll-like receptor 10 (TLR10)
      is associated with tumor size of papillary thyroid carcinoma in the Korean
      population.
AB  - Toll-like receptors (TLRs) are important components of innate immune response.
      The aim of this study was to investigate whether TLR gene cluster (TLR10-TLR1
      TLR6) polymorphisms are associated with the etiology of papillary thyroid
      carcinoma (PTC) and its clinicopathologic characteristics. We recruited 94 PTC
      patients and 325 control subjects. Genotypes for each SNP were determined by
      direct sequencing. SNPStats and SPSS 18.0 were used to evaluate odds ratios
      (ORs), 95 % confidence intervals (CIs), and P values. Multiple logistic
      regression analyzes of genetic data were performed. The missense SNP rs11466653
      was associated with small tumor size (<1 cm) in PTC. The frequency of the
      rs11466653 T allele was higher in PTC patients with tumors <1 cm in size than in
      the control group (95.8 vs. 87.2 %; P = 0.021, OR = 0.30, 95 % CI = 0.11-0.83).
      The T allele of rs11466653 (T/C, Met326Thr) in TLR10 may be a risk factor for the
      development of tumors in PTC in the Korean population.

PMID- 23124278
TI  - Risk factors for ulceration and amputation in diabetic foot: study in a cohort of
      496 patients.
AB  - Treatment strategies for foot at risk and diabetic foot are mainly preventive.
      Studies describing demographic data, clinical and impacting factors continue to
      be, however, scarce. Our objective was to determine the epidemiological
      presentation of diabetic foot and understand whether there were easily assessable
      variables capable of predicting the development of diabetic foot. This was a
      retrospective study of 496 patients with established foot at risk or diabetic
      foot, who were evaluated based on age, gender, type and duration of diabetes,
      foot at risk classification, and the presence of deformities, ulceration, and
      amputation. The presence of deformities, ulceration, and amputation was recorded
      in 45.9, 25.3, and 12.9 % of patients, respectively. As for diabetic foot
      classification, the great majority of our cohort had diabetic neuropathy (92.9
      %). Approximately 30 % had neuro-ischemic disease and only 7.1 % had ischemic
      disease alone. Sixty-two percent of patients presented neuropathy with no signs
      of arteriopathy. Foot classification was as a significant predictor for the
      presence of ulcer (p = 0.009; OR = 3.2; 95 % CI = 1.18-7.3). Only male gender was
      a significant predictor for ulceration (p < 0.001). Predictors of amputation were
      male gender (p < 0.001; OR = 3.44 95 % CI = 1.81-6.56) and neuro-ischemic
      diabetic foot (p < 0.049; OR = 4.6; 95 % CI = 1.01-20.9). The predictors for
      diabetic foot were male gender and the presence of neuropathy. The combination of
      neuropathy and peripheral vascular disease adds significantly to the risk for
      amputation among patients with the diabetic foot syndrome. Men, presenting
      combined risk factors, should be a group receiving special attention and in the
      foot clinic, due to their potentially worse evolution.

PMID- 23124281
TI  - Anaemia management in hospital patients: a UK perspective.

PMID- 23124280
TI  - 137Cs, 239,240Pu and 241Am in boreal forest soil and their transfer into wild
      mushrooms and berries.
AB  - Profiles of podzolic soil from boreal forests were sampled from eight sites in
      Finland and the distribution of (137)Cs in the soil layers was determined. In
      addition, (239,240)Pu and (241)Am were determined from two soil profiles taken at
      one sampling site. Inventories of (137)Cs in the soil profiles varied between 1.7
      kBq/m(2) and 42 kBq/m(2), reflecting known variation in (137)Cs fallout from the
      Chernobyl accident. The highest proportions of the radionuclides were found in
      the organic layer at a depth of less than 5 cm, which on average contained 47% of
      (137)Cs, 76% of (239,240)Pu and 79% of (241)Am. In the litter, clearly higher
      proportions of (137)Cs were found compared to (239,240)Pu and (241)Am, probably
      indicating its more effective recycling from the organic layer back to the
      surface. Only very minor proportions of (137)Cs were recorded below 20 cm. The
      concentration of (137)Cs in the soil profiles could be approximated with a
      declining logarithmic trend. The activity concentrations of (137)Cs were
      determined for six wild mushroom species and three wild berry species at two
      sites, as well as the aggregated transfer factors and the distribution of (137)Cs
      between their various parts. In addition, (239,240)Pu and (241)Am were determined
      in one mushroom and three berry species at one site. Very high concentrations of
      (137)Cs, up to 20 kBq/kg (d.w.), were found in mushrooms, and their transfer
      factors were between 0.1 m(2)/kg and 1.0 m(2)/kg. In berries, the transfer
      factors were an order of magnitude lower. (137)Cs accumulated more in the caps of
      mushrooms and in the fruits of berries than in other parts. Transfer factors for
      (239,240)Pu and (241)Am were two to three orders of magnitude lower than those of
      (137)Cs.

PMID- 23124279
TI  - Methicillin-resistant Staphylococcus aureus (MRSA) detected at four U.S.
      wastewater treatment plants.
AB  - BACKGROUND: The incidence of community-acquired methicillin-resistant
      Staphylococcus aureus (CA-MRSA) infections is increasing in the United States,
      and it is possible that municipal wastewater could be a reservoir of this
      microorganism. To date, no U.S. studies have evaluated the occurrence of MRSA in
      wastewater. OBJECTIVE: We examined the occurrence of MRSA and methicillin
      susceptible S. aureus (MSSA) at U.S. wastewater treatment plants. METHODS: We
      collected wastewater samples from two Mid-Atlantic and two Midwest wastewater
      treatment plants between October 2009 and October 2010. Samples were analyzed for
      MRSA and MSSA using membrane filtration. Isolates were confirmed using
      biochemical tests and PCR (polymerase chain reaction). Antimicrobial
      susceptibility testing was performed by Sensititre(r) microbroth dilution.
      Staphylococcal cassette chromosome mec (SCCmec) typing, Panton-Valentine
      leucocidin (PVL) screening, and pulsed field gel electrophoresis (PFGE) were
      performed to further characterize the strains. Data were analyzed by two-sample
      proportion tests and analysis of variance. RESULTS: We detected MRSA (n = 240)
      and MSSA (n = 119) in 22 of 44 (50%) and 24 of 44 (55%) wastewater samples,
      respectively. The odds of samples being MRSA-positive decreased as treatment
      progressed: 10 of 12 (83%) influent samples were MRSA-positive, while only one of
      12 (8%) effluent samples was MRSA-positive. Ninety-three percent and 29% of
      unique MRSA and MSSA isolates, respectively, were multidrug resistant. SCCmec
      types II and IV, the pvl gene, and USA types 100, 300, and 700 (PFGE strain types
      commonly found in the United States) were identified among the MRSA isolates.
      CONCLUSIONS: Our findings raise potential public health concerns for wastewater
      treatment plant workers and individuals exposed to reclaimed wastewater. Because
      of increasing use of reclaimed wastewater, further study is needed to evaluate
      the risk of exposure to antibiotic-resistant bacteria in treated wastewater.

PMID- 23124282
TI  - Time to intervene: patients who had  an in-hospital cardiorespiratory arrest.

PMID- 23124284
TI  - The MAGICC and practical approach to rheumatology transition.

PMID- 23124285
TI  - Comparison of juvenile and adult onset systemic lupus erythematosus.

PMID- 23124286
TI  - Juvenile idiopathic arthritis:  in adolescence and beyond.

PMID- 23124287
TI  - Anaemia in hospital practice.
AB  - This article describes the current problem of anaemia in hospital patients,
      functional iron deficiency and reviews the current roles of intravenous iron
      therapy. Attention to and correction of anaemia in the hospital patient may
      reduce the reliance for blood transfusion, with improvement in the patient's
      quality of life and outcomes.

PMID- 23124288
TI  - Ketamine cystitis: an emerging diagnostic and therapeutic challenge.
AB  - Ketamine abuse is increasingly common in the UK. Ketamine-induced cystitis can
      cause serious damage  to the urinary tract. This emerging problem presents a new
      diagnostic challenge and is very likely  to increase in incidence over the coming
      years.

PMID- 23124289
TI  - Pathogenesis of hepatitis B virus infection and potential for new therapies.
AB  - Chronic hepatitis B virus infection leads to about 1 million deaths per year,
      making it one of the top ten causes of death worldwide. An improved understanding
      of defective antiviral responses in chronic hepatitis B virus infection could
      allow specific immunotherapeutic interventions, enhancing the immune response to
      hepatitis B virus.

PMID- 23124290
TI  - Time to intervene? Lessons from the NCEPOD cardiopulmonary resuscitation report
      2012.

PMID- 23124291
TI  - An 85-year-old woman with acute back pain.

PMID- 23124292
TI  - Biliary cystadenocarcinoma complicated by intralesional haemorrhage.

PMID- 23124293
TI  - Testicular capillary haemangioma.

PMID- 23124294
TI  - Alexis Carrel receives the Nobel Prize for Medicine.

PMID- 23124295
TI  - Saving for your children's future.

PMID- 23124297
TI  - Should remifentanil be used for labour analgesia?

PMID- 23124298
TI  - Subhepatic appendicitis presenting  with right upper quadrant pain.

PMID- 23124299
TI  - Pulmonary embolism and patent foramen ovale causing an ischaemic stroke.

PMID- 23124300
TI  - Dental implant treatment after improvement of oral environment by orthodontic
      therapy.
AB  - A 57-year-old man presented with mesial inclination of the lower right first
      molar caused by untreated loss of the second premolar. The occlusal relationship
      was restored by dental implant treatment following improvement of the intraoral
      environment by orthodontic therapy. At his initial visit, the interdental spacing
      in the molar-premolar region was inadequate, as the first molar had mesially
      inclined into the extraction space of the second premolar. The patient had also
      lost the second molar and complained of masticatory problems on the right side.
      It was considered necessary to restore the second molar and improve the occlusal
      relationship with the first molar to recover occlusal function on the right side.
      After orthodontic therapy to correct the position of the mesially inclined tooth,
      occlusal restoration was carried out by dental implant treatment. The patient's
      clinical condition has remained excellent at over 5 years 2 months post
      surgically and the patient is satisfied with the treatment outcome. The
      combination of dental implant treatment and orthodontic therapy were effective in
      improving the intraoral environment in this patient, indicating the efficacy of
      interdisciplinary treatment planning and practice.

PMID- 23124301
TI  - A case of mucoepidermoid carcinoma associated with maxillary cyst.
AB  - We report a case of a mucoepidermoid carcinoma associated with a maxillary cyst.
      The patient was an 18-year-old man presenting with the chief complaint of left
      buccal swelling. The left maxillary third molar was semi-impacted in the
      direction of the crown on the buccal side. Orthopantomography revealed a cystic
      radiolucency extending over a wide area, ranging from the left maxilla to the
      maxillary sinus and nasal cavity. Computed tomography revealed a multilocular
      lesion surrounded by a thin shell of bone. Biopsy findings revealed a cystic
      lesion, but the cause could not be identified preoperatively. The cystic lesion
      was resected under general anesthesia. The lesion was multilocular and surrounded
      by a bone shell, and had expanded into the maxillary sinus. At the same time,
      indurated soft tissue adhering strongly to the palatine bone on the inferior
      palatine side of the lesion was resected. Histopathological examination showed a
      cystic lesion and mucoepidermoid carcinoma. An additional resection was planned
      and the maxilla partially resected. Mucoepidermoid carcinomas usually occur in
      the parotid and minor salivary glands, but in rare cases appear in the center of
      a jaw bone, almost always in the mandible. In the present case, the carcinoma was
      associated with a cystic lesion believed to have developed from maxillary bone
      and involved an impacted tooth adjacent to the tumor. This suggested a central
      mucoepidermoid carcinoma in the maxillary cyst. Postoperatively, the missing
      teeth have been replaced with a denture and the course has been good, with no
      recurrences or metastases identified.

PMID- 23124302
TI  - Autogenous bone graft combined with buccal fat pad as barrier in treatment of
      Class II furcation defect: a case report.
AB  - The treatment of furcation defects is a complex and difficult task that may
      compromise the success of periodontal therapy. Here we report a new clinical
      treatment of a Class II furcation defect using an autogenous bone graft
      associated with a buccal fat pad (BFP) used as a membrane. The surgical treatment
      was performed following initial periodontal therapy. Post-operative follow-up
      appointments were performed at 3, 7, and 12 months. Clinically, after 3 and 7
      months, a reduction in probing depth without bleeding on probing and an increase
      in vertical and horizontal clinical attachment level were observed. After 7 post
      operative months, an increase in keratinized gingiva was observed.
      Radiographically, a significant improvement was noted, with the furcation defect
      almost completely closed. These results could also be observed after 12
      postoperative months. It can be concluded that the combined use of autogenous
      bone graft and a BFP yielded clinically favorable outcome in the treatment of a
      mandibular Class II furcation defect.

PMID- 23124303
TI  - Case report of difficult dental prosthesis insertion due to severe gag reflex.
AB  - Susceptibility to the gag reflex may render insertion of removable dentures very
      difficult. The use of intravenous sedation in such cases allows for the
      fabrication of dentures with decreased discomfort to the patient. When the
      completed dentures are inserted, however, discomfort may still occur as the
      effects of the gag reflex will again be felt. We report a case of an edentulous
      maxillary patient who was unable to insert his dentures due to the gag reflex. A
      denture with a smaller than usual plate area was created so as to prevent anxiety
      occurring during insertion with subsequent triggering of the gag reflex. The
      dentures reached as far as the premolars. At first, long-term wear was difficult
      due to gagging at immediately after insertion. Full-time wear became possible,
      however, after approximately one and a half months. Hereafter, masticatory
      function will be enhanced through extension of the denture base and addition of
      artificial teeth in stages.

PMID- 23124304
TI  - Nonsurgical recovery of interdental papillae under supportive periodontal
      therapy.
AB  - We observed nonsurgical improvement of interdental papillae in a patient
      undergoing supportive periodontal therapy. The patient was a 47-year-old Japanese
      man presenting with widespread gingival recession at Daniele's papilla presence
      index level 3 and Miller Class I recession affecting the facial aspect of tooth
      number 42. Initial periodontal therapy for periodontitis was performed, included
      oral hygiene instruction, scaling and root planing, resulting in a reduction in
      inflammation. Use of an interdental brush was then suspended to allow the
      interdental papillae to recover. The type of toothbrush and tooth brushing method
      were checked repeatedly. Mechanical debridement was performed every 2 to 3
      months. A gradual improvement was observed in recession of the interdental
      papillae over a period of several years together with coronal regrowth of the
      gingival margin.

PMID- 23124305
TI  - Establishment and current status of patient community at Tokyo Dental College.
AB  - The "Dental students training to address the needs of each individual patient:
      enhancement of ability to make a comprehensive diagnosis and treatment plans with
      high ethical standards and good communication skills", project launched at Tokyo
      Dental College was adopted by the Ministry of Education, Culture, Sports, Science
      and Technology as part of its "Program for Promoting University Education and
      Student Support, Theme A: Program for Promoting University Education Reform" in
      2009. One of the main goals of this subject is "the establishment of Patient
      Community". Patient Community members allowed students to gain a more realistic
      experience of clinical practice than simulated patients. The Patient Community
      consists of patients and members of the parents' association who have agreed to
      cooperate for the advancement of dental education, becoming involved in dental
      student education through Communication Studies, which are held for first- to
      fourth-year students. Patient Community members were recruited at the open
      lectures (15 times, between July 10, 2010 and November 30, 2011). The Patient
      Community comprised 24 members, including 8 men and 16 women by November 30,
      2011. The cumulative number of attendees in Communication Studies (I-IV, 6 times)
      was 35, including 13 men and 22 women. Fourteen people applied for admission on
      the day of the open lecture. Seven people signed up between 1 and 7 days after
      the open lecture. On the other hand, only 3 people applied within 8 to 9 days
      after the open lecture. However, interestingly, the ratio of the attendance for
      Communication Studies by Patient Community members who applied 8 to 9 days after
      the open lecture was higher than that of members who applied for admission on the
      day of the open lecture. Since the number of Patient Community members is
      insufficient for the purposes of the Patient Community, it is necessary to think
      about how recruitment methods can be made more effective and how such open
      lectures should be conducted in future.

PMID- 23124306
TI  - Undergraduate students introduction to manual and rotary root canal
      instrumentation.
AB  - The aim of this study was to evaluate the performance of undergraduates in their
      first contact with manual and rotary root canal instrumentation. Forty-two
      students who had never worked on a root canal before instrumented 42 extracted
      lower-incisors. Participants were assigned to one of two groups: Rotary
      instrumentation or manual instrumentation. Pre- and post-operative computed
      tomography scans were obtained with a 3-dimensional dental imaging system.
      Starting and finishing times of preparation were recorded. The cross-sectional
      area of the root canal was analyzed with 2-mm-below-the-apex initial and final
      transverse images recorded through a digital imaging system and analyzed with
      software to measure the initial and final area of the root canal in mm(2). Data
      from the cross-sectional area of the root canal and time spent were subjected to
      the Mann-Whitney's U-test (p<0.05). The rotary instrumentation group showed
      smaller time for preparation (p=0.0204). No differences between rotary and manual
      instrumentation regarding the cross-sectional area of the root canal were
      observed (p=0.25). No accidents occurred. Undergraduate students showed good
      performance in their first contact with the manual and rotary instrumentation
      with regard to time spent and cross-sectional area of the root canal, with no
      operative accidents.

PMID- 23124307
TI  - Carbon nanomaterials for electronics, optoelectronics, photovoltaics, and
      sensing.
AB  - In the last three decades, zero-dimensional, one-dimensional, and two-dimensional
      carbon nanomaterials (i.e., fullerenes, carbon nanotubes, and graphene,
      respectively) have attracted significant attention from the scientific community
      due to their unique electronic, optical, thermal, mechanical, and chemical
      properties. While early work showed that these properties could enable high
      performance in selected applications, issues surrounding structural inhomogeneity
      and imprecise assembly have impeded robust and reliable implementation of carbon
      nanomaterials in widespread technologies. However, with recent advances in
      synthesis, sorting, and assembly techniques, carbon nanomaterials are
      experiencing renewed interest as the basis of numerous scalable technologies.
      Here, we present an extensive review of carbon nanomaterials in electronic,
      optoelectronic, photovoltaic, and sensing devices with a particular focus on the
      latest examples based on the highest purity samples. Specific attention is
      devoted to each class of carbon nanomaterial, thereby allowing comparative
      analysis of the suitability of fullerenes, carbon nanotubes, and graphene for
      each application area. In this manner, this article will provide guidance to
      future application developers and also articulate the remaining research
      challenges confronting this field.

PMID- 23124308
TI  - Archaic human genomics.
AB  - For much of the 20th century, the predominant view of human evolutionary history
      was derived from the fossil record. Homo erectus was seen arising in Africa from
      an earlier member of the genus and then spreading throughout the Old World and
      into the Oceania. A regional continuity model of anagenetic change from H.
      erectus via various intermediate archaic species into the modern humans in each
      of the regions inhabited by H. erectus was labeled the multiregional model of
      human evolution (MRE). A contrasting model positing a single origin, in Africa,
      of anatomically modern H. sapiens with some populations later migrating out of
      Africa and replacing the local archaic populations throughout the world with
      complete replacement became known as the recent African origin (RAO) model.
      Proponents of both models used different interpretations of the fossil record to
      bolster their views for decades. In the 1980s, molecular genetic techniques began
      providing evidence from modern human variation that allowed not only the
      different models of modern human origins to be tested but also the exploration
      demographic history and the types of selection that different regions of the
      genome and even specific traits had undergone. The majority of researchers
      interpreted these data as strongly supporting the RAO model, especially analyses
      of mitochondrial DNA (mtDNA). Extrapolating backward from modern patterns of
      variation and using various calibration points and substitution rates, a
      consensus arose that saw modern humans evolving from an African population around
      200,000 years ago. Much later, around 50,000 years ago, a subset of this
      population migrated out of Africa replacing Neanderthals in Europe and western
      Asia as well as archaics in eastern Asia and Oceania. mtDNA sequences from more
      than two-dozen Neanderthals and early modern humans re-enforced this consensus.
      In 2010, however, the complete draft genomes of Neanderthals and of heretofore
      unknown hominins from Siberia, called Denisovans, demonstrated gene flow between
      these archaic human species and modern Eurasians but not sub-Saharan Africans.
      Although the levels of gene flow may be very limited, this unexpected finding
      does not fit well with either the RAO model or MRE model. More thorough sampling
      of modern human diversity, additional fossil discoveries, and the sequencing of
      additional hominin fossils are necessary to throw light onto our origins and our
      history.

PMID- 23124309
TI  - Massive contamination of Exophiala dermatitidis and E. phaeomuriformis in railway
      stations in subtropical Turkey.
AB  - In order to reveal the source of contamination of opportunistic fungi, their
      natural habitat has to be understood. Black yeast-like fungi are abundant in man
      made environments, particularly in those that are rich in toxic hydrocarbons such
      as railway ties. In this study, we investigated the presence of black fungi on
      creosote-treated oak railway ties and concrete sleepers stained with petroleum
      oil. Samples were collected at two central stations in Turkish cities, Mersin and
      Adana, and from Tarsus town station located between these two. The sample
      locations had subtropical climates. A total of 570 railway samples, including 320
      from oak and 250 from concrete, were collected. Cotton swabs moistened with
      sterile physiological saline were applied to the ties and inoculated onto malt
      extract agar followed by incubation at 37  degrees C. Overall, we recovered 97
      black yeast-like fungi (17.0 % positive). Sixty-three fungi (19.7 %) were
      collected from creosote-treated oak, whereas 34 isolates (13.6 %) were derived
      from concrete; the difference was significant (P = 0.05). Identification using
      rDNA internal transcribed spacer revealed Exophiala dermatitidis (57.7 %) and
      Exophiala phaeomuriformis (42.3 %). This study suggested that hydrocarbons enrich
      these opportunistic black yeasts. An eventual health risk is discussed.

PMID- 23124310
TI  - mRNA expression of interleukins and Th1/Th2 imbalance in patients with pulmonary
      embolism.
AB  - Few studies have investigated the changes of Th1- and Th2-type cytokines in
      pulmonary embolism (PE) patients. In this study, the gene expression of
      interleukins and the balance of Th1- and Th2-type cytokines in the peripheral
      blood mononuclear cells (PBMCs) of PE patients and controls were investigated. A
      total of 20 PE patients and 20 gender- and age-matched controls were included in
      the study. Human cDNA microarray analysis was used to detect the differences in
      cytokine gene expression between the two groups and a random variance model
      corrected t-test was used to analyze the statistical data. In comparison with the
      controls, 12 genes were found to be downregulated, specifically IL1A, IL9, IL17B,
      IL19, IL23A, IL25 (p<0.05), IL2, IL3, IL13, IL22, IL24 and IL31 (p<0.01), and 2
      genes were found to be upregulated, specifically IL10 and IL28A, in the PE
      patients. The expression levels of IFN-gamma and IL2 mRNA in the PE patients were
      significantly lower than those in the control group (p<0.01), while the IL20 mRNA
      expression levels were significantly upregulated (p<0.01). We conclude that there
      are significant differences in interleukin gene expression between the PE
      patients and the control group. A shift of the Th1/Th2 balance comprising
      enhanced Th2 activity and reduced Th1 activity in the PE patients is also
      demonstrated. 

PMID- 23124318
TI  - Human endometrial stem cells as a new source for programming to neural cells.
AB  - Human EnSC (endometrial-derived stem cell) is an abundant and easily available
      source for cell replacement therapy. Many investigations have shown the potency
      of the cells to differentiate into several mesoderm-derived cell lineages,
      including osteocytes and adipocytes. Here, the potency of EnSC in neural
      differentiation has been investigated. Flow cytometric analysis showed that they
      were positive for CD90, CD105, OCT4, CD44 and negative for CD31, CD34, CD133. The
      characterized cells were induced into neural differentiation by bFGF (basic
      fibroblast growth factor), PDGF (platelet-derived growth factor) and EGF
      (epidermal growth factor) signalling molecules, respectively in a sequential
      protocol, and differentiated cells were analysed for expression of neuronal
      markers by RT-PCR (reverse transcription-PCR) and immunocytochemistry, including
      Nestin, GABA (gamma-aminobutyric acid), MAP2 (microtubule-associated protein 2),
      beta3-tub (class III beta-tubulin) and NF-L (neurofilament-light) at the level of
      their mRNAs. The expression of MAP2, beta3-tub and NF-L proteins in EnSC was
      confirmed 28 days PT (post-treatment) by immunocytochemistry. In conclusion, EnSC
      can respond to signalling molecules that are usually used as standards in neural
      differentiation and can programme neuronal cells, making these cells worth
      considering as a unique source for cell therapy in neurodegenerative disease.

PMID- 23124319
TI  - Incidence of myocardial infarction among cooks and other restaurant workers in
      Sweden 1987-2005.
AB  - OBJECTIVES: The aim of this study was to investigate the incidence of myocardial
      infarction (MI) among cooks and other restaurant workers. METHODS: A prospective
      cohort study comprised manual workers in the service sector in the Swedish
      National Census of 1985, totaling 543 497 women and 233 999 men. Restaurant
      workers were identified by occupational codes. Information on first time MI
      during 1987-2005 was obtained from nation-wide registers. We used Cox
      proportional hazards modeling, with separate analyses for men and women,
      adjusting for age, hypertension, diabetes, and socioeconomic status. RESULTS:
      Female cooks, restaurant and kitchen assistants, and wait staff all showed a
      statistically significant increase in risk of MI [hazard ratio (HR) 1.34, 95%
      confidence interval (95% CI) 1.21-1.48; HR 1.12, 95% CI 1.03-1.21; and HR 1.25,
      95% CI 1.06-1.47, respectively]. No increased risk was found among female cold
      buffet managers. Among men, there was no statistically significant increase in
      risk for any of these occupations. The association was not stronger for subjects
      working >=5 years. Group level information on smoking habits showed a similar
      percentage of daily smokers among female cooks compared to female manual workers
      in general. CONCLUSIONS: We found an increased risk of MI among female but not
      male cooks, restaurant and kitchen assistants, and wait staff. The excess risk
      may be related to occupational factors, but the results do not clearly support
      the hypothesis of cooking fumes as a risk factor for MI. Job strain could be a
      potential explanation for the findings.

PMID- 23124320
TI  - Comparison of urinary biomarkers for early detection of acute kidney injury after
      cardiopulmonary bypass surgery in infants and young children.
AB  - Acute kidney injury (AKI) is a potential complication for children with
      congenital heart disease (CHD) after cardiopulmonary bypass (CPB) surgery. This
      study was designed to investigate and compare the predictive values of urinary
      biomarkers for AKI after CPB surgery in infants and young children and to
      determine the optimal timing of testing and the cutoff value for each biomarker.
      The study prospectively enrolled 58 CHD children 3 years of age or younger who
      were undergoing CPB surgery. Urinary neutrophil gelatinase-associated lipocalin
      (NGAL), interleukin-18 (IL-18), microalbumin (MA), N-acetyl-beta-D
      glucosaminidase (NAG), alpha1-microglobulin (alpha1-MG), and creatinine (UCr)
      were measured at baseline and at various time points after surgery. Children who
      experienced AKI had more complex cardiac surgical procedures as evaluated by Risk
      Adjustment for Congenital Heart Surgery 1 (RACHS-1), longer CPB and aortic
      clamping times, and worse clinical outcomes than those who did not. In the AKI
      group, all five urinary biomarkers increased substantially and peaked at 4 h
      after surgery. In contrast, in the non-AKI group, they increased slightly or had
      no significant changes during the first 24 h. All the biomarkers had the best
      predictive performances at 4 h after surgery. At this time point, NAG had the
      minimum area under the curve (AUC) (0.747), which was significantly lower than
      that of the others (AUC, 0.82-0.85; P < 0.05). The optimal cutoff value of each
      biomarker was 290 ng/mg UCr for NAGL, 1,477 pg/mg UCr for IL-18, 400 mg/g UCr for
      MA, 225 U/g UCr for NAG, and 290 mg/g UCr for alpha1-MG. In conclusion, urinary
      NGAL, IL-18, MA, and alpha1-MG had similar predictive performances for the early
      detection of AKI after CPB surgery in infants and young children.

PMID- 23124321
TI  - A pilot open-label phase II trial of rituximab for non-criteria manifestations of
      antiphospholipid syndrome.
AB  - OBJECTIVE: The primary objective of this study was to evaluate the safety of
      rituximab in antiphospholipid antibody (aPL)-positive patients with non-criteria
      manifestations of antiphospholipid syndrome (APS). The secondary objectives were
      to evaluate the effect of rituximab on the aPL profile and to evaluate the
      efficacy of rituximab treatment for non-criteria manifestations of APS. METHODS:
      In this 12-month, phase II pilot study, adult aPL-positive patients with
      thrombocytopenia, cardiac valve disease, skin ulcer, aPL nephropathy, and/or
      cognitive dysfunction received 2 doses of rituximab (1,000 mg) on days 1 and 15.
      Antiphospholipid antibody profiles and clinical outcome measures, which were
      categorized as complete response, partial response, no response, or recurrence,
      were analyzed at preset time points. RESULTS: Two of 19 patients experienced
      infusion reactions, resulting in early termination. Twelve serious adverse events
      and 49 nonserious adverse events were recorded. All patients who had positive
      results of lupus anticoagulant, anticardiolipin, and anti-beta(2)-glycoprotein I
      antibody tests at baseline had positive results at 24 weeks and 52 weeks. The
      numbers of patients with a complete response, a partial response, no response,
      and recurrence for the clinical outcome measures at 24 weeks were as follows: for
      thrombocytopenia, 1, 1, 2, and 0, respectively; for cardiac valve disease, 0, 0,
      3, and not analyzed, respectively; for skin ulcer, 3, 1, 0, and 1, respectively;
      for aPL nephropathy, 0, 1, 0, and 0, respectively; and for cognitive dysfunction,
      3, 1, 1, and not analyzed, respectively. CONCLUSION: The results of this
      uncontrolled and nonrandomized pilot study suggest that the safety of rituximab
      in aPL-positive patients is consistent with the safety profile of rituximab.
      Despite causing no substantial change in aPL profiles, rituximab may be effective
      in controlling some but not all non-criteria manifestations of APS.

PMID- 23124322
TI  - Tnt1 retrotransposon mutagenesis: a tool for soybean functional genomics.
AB  - Insertional mutagenesis is a powerful tool for determining gene function in both
      model and crop plant species. Tnt1, the transposable element of tobacco
      (Nicotiana tabacum) cell type 1, is a retrotransposon that replicates via an RNA
      copy that is reverse transcribed and integrated elsewhere in the plant genome.
      Based on studies in a variety of plants, Tnt1 appears to be inactive in normal
      plant tissue but can be reactivated by tissue culture. Our goal was to evaluate
      the utility of the Tnt1 retrotransposon as a mutagenesis strategy in soybean
      (Glycine max). Experiments showed that the Tnt1 element was stably transformed
      into soybean plants by Agrobacterium tumefaciens-mediated transformation. Twenty
      seven independent transgenic lines carrying Tnt1 insertions were generated.
      Southern-blot analysis revealed that the copy number of transposed Tnt1 elements
      ranged from four to 19 insertions, with an average of approximately eight copies
      per line. These insertions showed Mendelian segregation and did not transpose
      under normal growth conditions. Analysis of 99 Tnt1 flanking sequences revealed
      insertions into 62 (62%) annotated genes, indicating that the element
      preferentially inserts into protein-coding regions. Tnt1 insertions were found in
      all 20 soybean chromosomes, indicating that Tnt1 transposed throughout the
      soybean genome. Furthermore, fluorescence in situ hybridization experiments
      validated that Tnt1 inserted into multiple chromosomes. Passage of transgenic
      lines through two different tissue culture treatments resulted in Tnt1
      transposition, significantly increasing the number of insertions per line. Thus,
      our data demonstrate the Tnt1 retrotransposon to be a powerful system that can be
      used for effective large-scale insertional mutagenesis in soybean.

PMID- 23124323
TI  - Comparative analysis of syntenic genes in grass genomes reveals accelerated rates
      of gene structure and coding sequence evolution in polyploid wheat.
AB  - Cycles of whole-genome duplication (WGD) and diploidization are hallmarks of
      eukaryotic genome evolution and speciation. Polyploid wheat (Triticum aestivum)
      has had a massive increase in genome size largely due to recent WGDs. How these
      processes may impact the dynamics of gene evolution was studied by comparing the
      patterns of gene structure changes, alternative splicing (AS), and codon
      substitution rates among wheat and model grass genomes. In orthologous gene sets,
      significantly more acquired and lost exonic sequences were detected in wheat than
      in model grasses. In wheat, 35% of these gene structure rearrangements resulted
      in frame-shift mutations and premature termination codons. An increased codon
      mutation rate in the wheat lineage compared with Brachypodium distachyon was
      found for 17% of orthologs. The discovery of premature termination codons in 38%
      of expressed genes was consistent with ongoing pseudogenization of the wheat
      genome. The rates of AS within the individual wheat subgenomes (21%-25%) were
      similar to diploid plants. However, we uncovered a high level of AS pattern
      divergence between the duplicated homeologous copies of genes. Our results are
      consistent with the accelerated accumulation of AS isoforms, nonsynonymous
      mutations, and gene structure rearrangements in the wheat lineage, likely due to
      genetic redundancy created by WGDs. Whereas these processes mostly contribute to
      the degeneration of a duplicated genome and its diploidization, they have the
      potential to facilitate the origin of new functional variations, which, upon
      selection in the evolutionary lineage, may play an important role in the origin
      of novel traits.

PMID- 23124324
TI  - Arabidopsis response Regulator1 and Arabidopsis histidine phosphotransfer
      Protein2 (AHP2), AHP3, and AHP5 function in cold signaling.
AB  - The Arabidopsis (Arabidopsis thaliana) two-component signaling system, which is
      composed of sensor histidine kinases, histidine phosphotransfer proteins, and
      response regulators, mediates the cytokinin response and various other plant
      responses. We have previously shown that ARABIDOPSIS HISTIDINE KINASE2 (AHK2),
      AHK3, and cold-inducible type A ARABIDOPSIS RESPONSE REGULATORS (ARRs) play roles
      in cold signaling. However, the roles of type B ARRs and ARABIDOPSIS HISTIDINE
      PHOSPHOTRANSFER PROTEINS (AHPs) have not been investigated in cold signaling.
      Here, we show that ARR1 and AHP2, AHP3, and AHP5 play positive roles in the cold
      inducible expression of type A ARRs. arr1 mutants showed greatly reduced cold
      responsive expression of type A ARRs compared with the wild type, whereas ARR1
      overexpressing Arabidopsis exhibited the hypersensitive cold response of type A
      ARRs as well as enhanced freezing tolerance with cytokinin, suggesting that ARR1
      functions as a positive factor of cold signaling. Transgenic Arabidopsis
      expressing ARR1DeltaDDK:GR lacking the amino-terminal receiver domain showed wild
      type expression levels of type A ARRs in response to cold, indicating that the
      signal receiver domain of ARR1 might be important for cold-responsive expression
      of type A ARRs. ahp2 ahp3 ahp5 triple mutations greatly reduced type A ARR
      expression in response to cold, whereas the single or double ahp mutants
      displayed wild-type levels of ARR expression, suggesting that AHP2, AHP3, and
      AHP5 are redundantly involved in cold signaling. Taken together, these results
      suggest that ARR1 mediates cold signal via AHP2, AHP3, or AHP5 from AHK2 and AHK3
      to express type A ARRs. We further identified a cold transcriptome affected by
      ahk2 ahk3 mutations by microarray analysis, revealing a new cold-responsive gene
      network regulated downstream of AHK2 and AHK3.

PMID- 23124325
TI  - Loose Plant Architecture1, an INDETERMINATE DOMAIN protein involved in shoot
      gravitropism, regulates plant architecture in rice.
AB  - Tiller angle and leaf angle are two important components of rice (Oryza sativa)
      plant architecture that play a crucial role in determining grain yield. Here, we
      report the cloning and characterization of the Loose Plant Architecture1 (LPA1)
      gene in rice, the functional ortholog of the AtIDD15/SHOOT GRAVITROPISM5 (SGR5)
      gene in Arabidopsis (Arabidopsis thaliana). LPA1 regulates tiller angle and leaf
      angle by controlling the adaxial growth of tiller node and lamina joint. LPA1 was
      also found to affect shoot gravitropism. Expression pattern analysis suggested
      that LPA1 influences plant architecture by affecting the gravitropism of leaf
      sheath pulvinus and lamina joint. However, LPA1 only influences gravity
      perception or signal transduction in coleoptile gravitropism by regulating the
      sedimentation rate of amyloplasts, distinct from the actions of LAZY1. LPA1
      encodes a plant-specific INDETERMINATE DOMAIN protein and defines a novel
      subfamily of 28 INDETERMINATE DOMAIN proteins with several unique conserved
      features. LPA1 is localized in the nucleus and functions as an active
      transcriptional repressor, an activity mainly conferred by a conserved ethylene
      response factor-associated amphiphilic repression-like motif. Further analysis
      suggests that LPA1 participates in a complicated transcriptional and protein
      interaction network and has evolved novel functions distinct from SGR5. This
      study not only facilitates the understanding of gravitropism mechanisms but also
      generates a useful genetic material for rice breeding.

PMID- 23124326
TI  - Pattern of auxin and cytokinin responses for shoot meristem induction results
      from the regulation of cytokinin biosynthesis by AUXIN RESPONSE FACTOR3.
AB  - De novo organ regeneration is an excellent biological system for the study of
      fundamental questions regarding stem cell initiation, cell fate determination,
      and hormone signaling. Despite the general belief that auxin and cytokinin
      responses interact to regulate de novo organ regeneration, the molecular
      mechanisms underlying such a cross talk are little understood. Here, we show that
      spatiotemporal biosynthesis and polar transport resulted in local auxin
      distribution in Arabidopsis (Arabidopsis thaliana), which in turn determined the
      cytokinin response during de novo shoot regeneration. Genetic and pharmacological
      interference of auxin distribution disrupted the cytokinin response and ATP/ADP
      ISOPENTENYLTRANSFERASE5 (AtIPT5) expression, affecting stem cell initiation and
      meristem formation. Transcriptomic data suggested that AUXIN RESPONSE FACTOR3
      (ARF3) mediated the auxin response during de novo organ regeneration. Indeed,
      mutations in ARF3 caused ectopic cytokinin biosynthesis via the misexpression of
      AtIPT5, and this disrupted organ regeneration. We further showed that ARF3
      directly bound to the promoter of AtIPT5 and negatively regulated AtIPT5
      expression. The results from this study thus revealed an auxin-cytokinin cross
      talk mechanism involving distinct intermediate signaling components required for
      de novo stem cell initiation and shed new light on the mechanisms of
      organogenesis in planta.

PMID- 23124327
TI  - Transcription activator-like effector nucleases enable efficient plant genome
      engineering.
AB  - The ability to precisely engineer plant genomes offers much potential for
      advancing basic and applied plant biology. Here, we describe methods for the
      targeted modification of plant genomes using transcription activator-like
      effector nucleases (TALENs). Methods were optimized using tobacco (Nicotiana
      tabacum) protoplasts and TALENs targeting the acetolactate synthase (ALS) gene.
      Optimal TALEN scaffolds were identified using a protoplast-based single-strand
      annealing assay in which TALEN cleavage creates a functional yellow fluorescent
      protein gene, enabling quantification of TALEN activity by flow cytometry. Single
      strand annealing activity data for TALENs with different scaffolds correlated
      highly with their activity at endogenous targets, as measured by high-throughput
      DNA sequencing of polymerase chain reaction products encompassing the TALEN
      recognition sites. TALENs introduced targeted mutations in ALS in 30% of
      transformed cells, and the frequencies of targeted gene insertion approximated
      14%. These efficiencies made it possible to recover genome modifications without
      selection or enrichment regimes: 32% of tobacco calli generated from protoplasts
      transformed with TALEN-encoding constructs had TALEN-induced mutations in ALS,
      and of 16 calli characterized in detail, all had mutations in one allele each of
      the duplicate ALS genes (SurA and SurB). In calli derived from cells treated with
      a TALEN and a 322-bp donor molecule differing by 6 bp from the ALS coding
      sequence, 4% showed evidence of targeted gene replacement. The optimized reagents
      implemented in plant protoplasts should be useful for targeted modification of
      cells from diverse plant species and using a variety of means for reagent
      delivery.

PMID- 23124328
TI  - Phylogenetic analysis based on 28S rRNA of Babesia spp. in ruminants in China.
AB  - Molecular phylogenetic analyses are mainly based on the small ribosomal RNA
      subunit (18S rRNA), internal transcribed spacer regions, and other molecular
      markers. We compared the phylogenetic relationships of Babesia spp. using large
      subunit ribosomal RNA, i.e., 28S rRNA, and the united 28S + 18S rRNA sequence
      fragments from 11 isolates of Babesia spp. collected in China. Due to sequence
      length and variability, the 28S rRNA gene contained more information than the 18S
      rRNA gene and could be used to elucidate the phlyogenetic relationships of B.
      motasi, B. major, and B. bovis. Thus, 28S rRNA is another candidate marker that
      can be used for the phylogenetic analysis of Babesia spp. However, the united
      fragment (28S + 18S) analysis provided better supported phylogenetic
      relationships than single genes for Babesia spp. in China.

PMID- 23124330
TI  - Visualization of surface plasmon interference by imprinting intensity patterns on
      a photosensitive polymer.
AB  - We report on sub-wavelength structuring of photosensitive azo-containing polymer
      films induced by a surface plasmon interference intensity pattern. The two
      surface plasmon waves generated at neighboring nano-slits in the metal layer
      during irradiation interfere constructively, resulting in an intensity pattern
      with a periodicity three times smaller than the wavelength of the incoming light.
      The near field pattern interacts with the photosensitive polymer film placed
      above it, leading to a topography change which follows the intensity pattern
      exactly, resulting in the formation of surface relief gratings of a size below
      the diffraction limit. We analyze numerically and experimentally how the depth of
      the nano-slit alters the interference pattern of surface plasmons and find that
      the sub-wavelength patterning of the polymer surface could be optimized by
      modifying the geometry and the size of the nano-slit.

PMID- 23124331
TI  - Provisioning of bioavailable carbon between the wet and dry phases in a semi-arid
      floodplain.
AB  - Ecosystem functioning on arid and semi-arid floodplains may be described by two
      alternate traditional paradigms. The pulse-reserve model suggests that rainfall
      is the main driver of plant growth and subsequent carbon and energy reserve
      formation in the soil of arid and semi-arid regions. The flood pulse concept
      suggests that periodic flooding facilitates the two-way transfer of materials
      between a river and its adjacent floodplain, but focuses mainly on the period
      when the floodplain is inundated. We compared the effects of both rainfall and
      flooding on soil moisture and carbon in a semi-arid floodplain to determine the
      relative importance of each for soil moisture recharge and the generation of a
      bioavailable organic carbon reserve that can potentially be utilised during the
      dry phase. Flooding, not rainfall, made a substantial contribution to moisture in
      the soil profile. Furthermore, the growth of aquatic macrophytes during the wet
      phase produced at least an order of magnitude more organic material than rainfall
      induced pulse-reserve responses during the dry phase, and remained as
      recognizable soil carbon for years following flood recession. These observations
      have led us to extend existing paradigms to encompass the reciprocal provisioning
      of carbon between the wet and dry phases on the floodplain, whereby, in addition
      to carbon fixed during the dry phase being important for driving biogeochemical
      transformations upon return of the next wet phase, aquatic macrophyte carbon
      fixed during the wet phase is recognized as an important source of energy for the
      dry phase. Reciprocal provisioning presents a conceptual framework on which to
      formulate questions about the resistance and ecosystem resilience of arid and
      semi-arid floodplains in the face of threats like climate change and alterations
      to flood regimes.

PMID- 23124329
TI  - Pipeline embolization device for intracranial aneurysm: a systematic review.
AB  - INTRODUCTION: The pipeline embolization device (PED) is a new endovascular stent
      designed for the treatment of challenging intracranial aneurysms (IAs). Its use
      has been extended to nonruptured and ruptured IAs of a variety of configurations
      and etiologies in both the anterior and posterior circulations. METHODS: We
      conducted a systematic review of ten eligible reports on its clinical efficacy
      and safety. RESULTS: There were 414 patients with 448 IAs. The majority of the
      IAs were large (40.2 %), saccular or blister-like (78.3 %), and were located
      mostly in the anterior circulation (83.5 %). The regimens of antiplatelet therapy
      varied greatly between and within studies. The mean number of the PED used was
      2.0 per IA. Deployment was successful in around 95 % of procedures. Aneurysm
      obliteration was achieved in 82.9 % of IAs at 6-month. The overall incidences of
      periprocedural intracranial vascular complication rate and mortality rate were
      6.3 and 1.5 %, respectively. CONCLUSION: The PED is a safe and effective
      treatment for nonruptured IAs. Its use in the context of acute subarachnoid
      hemorrhage (SAH) should be cautioned. Its main limitations include the need for
      prolonged antiplatelet therapy, as well as the potential risks of IA rupture and
      non-IA-related intracerebral hemorrhages (ICH). Future studies should aim at
      identifying factors that predispose to incomplete obliteration, delayed rupture,
      and thromboembolic complications.

PMID- 23124332
TI  - Multifunctional bracts enhance plant fitness during flowering and seed
      development in Rheum nobile (Polygonaceae), a giant herb endemic to the high
      Himalayas.
AB  - Specialized bracts are thought to be important for the successful reproduction of
      some plants and are regarded as adaptations to diverse driving forces. However,
      few empirical studies have quantified the adaptive significance of bracts within
      a cost-benefit framework. We explored the adaptive significance of large and
      showy bracts for reproduction in Rheum nobile, a giant herb endemic to the high
      Himalayas. We examined whether the bracts enhance reproductive success during
      flowering and seed development. Bracts increased flower and fruit temperature on
      sunny days, greatly decreased the intensity of ultraviolet-B (UV-B) radiation
      reaching flowers and fruits, and prevented pollen grains being washed away by
      rain. Experiments indicated that high temperature could promote pollen
      germination, while pollen grains exposed to rain and UV-B radiation at ambient
      levels were seriously damaged. Furthermore, bract removal decreased the number of
      pollinators visiting flowers. When bracts were removed before or after flowering,
      fecundity and progeny quality were adversely affected, but seed predation by
      larvae of pollinators decreased. A cost-benefit analysis demonstrated that the
      cost of bracts, i.e., increased seed predation, is modest. Our results suggest
      that the bracts of R. nobile promote pollen germination, protect pollen grains
      from rain and intense UV-B radiation, enhance pollinator visitation during
      flowering, and facilitate the development of fertilized ovules during seed
      development. We conclude that multifunctional bracts of R. nobile are an
      effective adaptive strategy in alpine environments and might have been selected
      for because of abiotic environmental conditions as well as for enhancing
      pollination success.

PMID- 23124333
TI  - Prey selectivity affects reproductive success of a corallivorous reef fish.
AB  - Most animals consume a narrower range of food resources than is potentially
      available in the environment, but the underlying basis for these preferences is
      often poorly understood. Foraging theory predicts that prey selection should
      represent a trade-off between prey preferences based on nutritional value and
      prey availability. That is, species should consume preferred prey when available,
      but select less preferred prey when preferred prey is rare. We employed both
      field observation and laboratory experiments to examine the relationship between
      prey selection and preferences in the obligate coral-feeding filefish,
      Oxymonacanthus longirostris. To determine the drivers of prey selection, we
      experimentally established prey preferences in choice arenas and tested the
      consequences of prey preferences for key fitness-related parameters. Field
      studies showed that individuals fed almost exclusively on live corals from the
      genus Acropora. While diet was dominated by the most abundant species, Acropora
      nobilis, fish appeared to preferentially select rarer acroporids, such as A.
      millepora and A. hyacinthus. Prey choice experiments confirmed strong preferences
      for these corals, suggesting that field consumption is constrained by
      availability. In a longer-term feeding experiment, reproductive pairs fed on non
      preferred corals exhibited dramatic reductions to body weight, and in hepatic and
      gonad condition, compared with those fed preferred corals. The majority of pairs
      fed preferred corals spawned frequently, while no spawning was observed for any
      pairs fed a non-preferred species of coral. These experiments suggest that fish
      distinguish between available corals based on their intrinsic value as prey, that
      reproductive success is dependent on the presence of particular coral species,
      and that differential loss of preferred corals could have serious consequences
      for the population success of these dietary specialists.

PMID- 23124334
TI  - The novel biological action of antimicrobial peptides via apoptosis induction.
AB  - Antimicrobial peptides (AMPs) exert antimicrobial activity against Gram-positive
      and Gram-negative bacteria, fungi, and viruses by various mechanisms. AMPs
      commonly possess particular characteristics by harboring cationic and amphipathic
      structures and binding to cell membranes, resulting in the leakage of essential
      cell contents by forming pores or disturbing lipid organization. These membrane
      disruptive mechanisms of AMPs are possible to explain according to the various
      structure forming pores in the membrane. Some AMPs inhibit DNA and/or RNA
      synthesis as well as apoptosis induction by reactive oxygen species (ROS)
      accumulation and mitochondrial dysfunction. Specifically, mitochondria play a
      major role in the apoptotic pathway. During apoptosis induced by AMPs, cells
      undergo cytochrome c release, caspase activation, phosphatidylserine
      externalization, plasma or mitochondrial membrane depolarization, DNA and nuclei
      damage, cell shrinkage, apoptotic body formation, and membrane blebbing. Even
      AMPs, which have been reported to exert membrane-active mechanisms, induce
      apoptosis in yeast. These phenomena were also discovered in tumor cells treated
      with AMPs. The apoptosis mechanism of AMPs is available for various therapeutics
      such as antibiotics for antibiotic-resistant pathogens that resist to the
      membrane active mechanism, and antitumor agents with selectivity to tumor cells.

PMID- 23124335
TI  - Comparison of multilocus sequence typing (MLST) and repetitive sequence-based PCR
      (rep-PCR) fingerprinting for differentiation of Campylobacter jejuni isolated
      from broiler in Chiang Mai, Thailand.
AB  - We compared rapid fingerprinting using repetitive sequence-based PCR (rep-PCR)
      for subtyping Campylobacter jejuni isolates to the widely used multilocus
      sequence typing (MLST). Representative C. jejuni isolates (n = 16) from broilers
      were analyzed using MLST and rep-PCR. Both techniques demonstrated an equal
      discriminatory power of 0.8917, and 9 subgroups were identified. Clonal
      identification of all 16 isolates was identical for both techniques. The rep-PCR
      as described in this study may be used as a rapid and cost-effective alternative
      for subtyping of C. jejuni isolates, or as an effective screening tool in large
      epidemiological studies.

PMID- 23124336
TI  - Metabolic roles of carotenoid produced by non-photosynthetic bacterium Gordonia
      alkanivorans SKF120101.
AB  - Carotenoids produced by non-photosynthetic bacteria protect organisms against
      lethal photodynamic reactions and scavenge oxygenic radicals. However, the
      carotenoid produced by Gordonia alkanivorans SKF120101 is coupled to reducing
      power generation. SKF120101 selectively produces carotenoid under light
      conditions. The growth yield of SKF120101 cultivated under light conditions was
      higher than that under dark condition. In the cyclic voltammetry, both upper and
      lower voltammograms for neutral red (NR) immobilized in intact cells of SKF120101
      were not shifted in the condition without external redox sources but were
      commonly shifted downward by glucose addition and light. Electric current
      generation in a biofuel cell system (BFCS) catalyzed by harvested cells of
      SKF120101 was higher under light than dark condition. The ratio of electricity
      generation to glucose consumption by SKF120101 cultivated in BFCS was higher
      under light than dark condition. The carotenoid produced by SKF120101 catalyzes
      production of reducing power from light energy, first evaluated by the
      electrochemical technique used in this research.

PMID- 23124337
TI  - New geldanamycin analogs from Streptomyces hygroscopicus.
AB  - Geldanamycin (GM) and its analogs are important anticancer agents that inhibit
      heat shock protein (Hsp) 90, which is a major chaperone protein in cancer cells.
      Accordingly, based on interest in obtaining novel natural GM derivatives, the
      potential of Streptomyces hygroscopicus JCM4427, a GM producer, was explored for
      novel natural GM derivative(s), resulting in the discovery of new GM analogs as a
      biosynthetic shunt product and intermediates from its fermentation broth. In this
      study, the fermentation, isolation, structure determination, and biological
      activity of the compounds, two new tetracyclic thiazinogeldanamycin (1) and 19
      hydroxy-4,5-dihydrogeldanamycin (3), together with the three known 4,5
      dihydrothiazinogeldanamycin (2), reblastatin (4), and 17-demethoxy-reblastatin
      (5), are described.

PMID- 23124338
TI  - An antitumor component from Fomitiporia ellipsoidea.
AB  - A natural furan derivative was isolated from the methanolic extract of the fruit
      bodies of Fomitiporia ellipsoidea. Its chemical structure was elucidated as
      methyl 3,5-dioxo- 1,3,5,7-tetrahydrobenzo[1,2-c:4,5-c']difuran-4-carboxylate by
      means of extensive NMR and MS data analysis, and named as fomitiporiaester A (1).
      Compound 1 showed significant antitumor activity to hepatoma H(22) in vivo, and
      the inhibition rates were 42.94%, 49.17%, and 58.15% at concentrations of 5, 10,
      and 20 mg/kg, respectively. Compound 1 showed weak cytotoxic activities against
      the human hepatoblastoma (HepG-2) and human oophoroma (Skov 3) cell lines with
      IC(50) values of more than 100 MUM.

PMID- 23124339
TI  - Long-term repeated-batch operation of immobilized Escherichia coli cells to
      synthesize galactooligosaccharide.
AB  - In this study, we investigated whether galactooligosaccharide (GOS) can be stably
      and steadily synthesized using immobilized beta-galactosidase (beta-gal)
      inclusion body (IB)- containing E. coli cells during long-term repeated-batch
      operation. To improve the operational stability of this enzyme reactor system,
      immobilized E. coli cells were crosslinked with glutaraldehyde (GA) after
      immobilization of the E. coli. When we treated with 2% GA for E. coli
      crosslinking, GOS production continued to an elapsed time of 576 h, in which
      seven batch runs were operated consecutively. GOS production ranged from 51.6 to
      78.5 g/l (71.2 +/- 10.5 g/l, n = 7) during those batch operations. In contrast,
      when we crosslinked E. coli with 4% GA, GOS production ranged from 31.5 to 64.0
      g/l (52.3 +/- 10.8, n = 4), and only four consecutive batch runs were operated.
      Although we did not use an industrial beta-gal for GOS production, in which a
      thermophile is used routinely, this represents the longest operation time for GOS
      production using E. coli beta-gal. Improved stability and durability of the cell
      immobilization system were achieved using the crosslinking protocol. This
      strategy could be directly applied to other microbial enzyme reactor systems
      using cell immobilization to extend the operation time and/or improve the reactor
      system stability.

PMID- 23124340
TI  - Study of the rheological properties of a fermentation broth of the fungus
      Beauveria bassiana in a bioreactor under different hydrodynamic conditions.
AB  - Fermentation with filamentous fungi in a bioreactor is a complex dynamic process
      that is affected by flow conditions and the evolution of the rheological
      properties of the medium. These properties are mainly affected by the biomass
      concentration and the morphology of the fungus. In this work, the rheological
      properties of a fermentation with the fungus Beauveria bassiana under different
      hydrodynamic conditions were studied and the rheological behavior of this broth
      was simulated through a mixture of carboxymethyl cellulose sodium and cellulose
      fibers (CMCNa-SF). The bioreactor was a 10 L CSTR tank operated at different stir
      velocities. Rheological results were similar at 100 and 300 rpm for both systems.
      However, there was a significant increase in the viscosity accompanied by a
      change in the consistence index, calculated according to the power law model, for
      both systems at 800 rpm. The systems exhibited shear-thinning behavior at all
      stir velocities, which was determined with the power law model. The mixing time
      was observed to increase as the cellulose content in the system increased and,
      consequently, the efficiency of mixing diminished. These results are thought to
      be due to the rheological and morphological similarities of the two fungal
      systems. These results will help in the optimization of scale-up production of
      these fungi.

PMID- 23124341
TI  - Purification and characterization of a thermophilic cellulase from a novel
      cellulolytic strain, Paenibacillus barcinonensis.
AB  - A novel bacterial strain, MG7, with high cellulase activity was isolated and
      identified by morphological characteristics and molecular phylogeny analysis as
      Paenibacillus barcinonensis. Maximum production of cellulase by MG7 was observed
      at pH 7.0 and 35 degrees C. The enzyme was purified with a specific activity of
      16.88 U/mg, the cellulase activity was observed in a zymogram, and its molecular
      mass (58.6 kDa) was confirmed by SDS-PAGE. The purified enzyme showed maximum
      activity at pH 6.0 and 65 degrees C and degraded cellulosic substrates such as
      carboxy methyl cellulose (CMC), Avicel, filter paper, and beta-glucan. The enzyme
      showed stability with 0.5% concentration of various surfactants. The K(m) and
      V(max) of cellulase for CMC and Avicel were found to be 0.459 mg/ml and 10.46
      mg/ml/h, and 1.01 mg/ml and 10.0 mg/ml/h, respectively. The high catalytic
      activity and its stability to temperature, pH, surfactants, and metal ions
      indicated that the cellulase enzyme by MG7 is a good candidate for
      biotechnological applications.

PMID- 23124342
TI  - Evaluation of the probiotic potential of Bacillus polyfermenticus CJ6 isolated
      from Meju, a Korean soybean fermentation starter.
AB  - To evaluate the probiotic potential of Bacillus polyfermenticus CJ6 isolated from
      meju, a Korean traditional soybean fermentation starter, its functionality and
      safety were investigated. B. polyfermenticus CJ6 was sensitive to all antibiotics
      listed by the European Food Safety Authority. The strain was also non-hemolytic,
      carried no emetic toxin or enterotoxin genes, and produced no enterotoxins. The
      resistance of B. polyfermenticus CJ6 vegetative cells and spores to simulated
      gastrointestinal conditions was high (60-100% survival rate). B. polyfermenticus
      CJ6 produced high amounts (0.36 g as a purified lyophilized form) of gamma
      polyglutamic acid (PGA). We speculate that the improved cell viability and the
      production of gamma-PGA have a significant correlation. Adhesion of the strain to
      Caco-2 and HT-29 cells was weaker than that of the reference strain (Lb.
      rhamnosus GG), but it was comparable to or stronger than those of reported
      Bacillus spp. When B. polyfermenticus CJ6 spores were given orally to mice, the
      number of cells excreted in the feces was 4-fold higher than the original
      inocula. This suggests the inoculated spores propagated within the intestinal
      tract of the mice. This idea was confirmed by field emission scanning electron
      microscopy, which revealed directly that B. polyfermenticus CJ6 cells germinated
      and adhered within the gastrointestinal tract of mice. Taken together, these
      findings suggest that B. polyfermenticus CJ6 has probiotic potential for both
      human consumption and use in animal feeds.

PMID- 23124343
TI  - Development of a chemically defined minimal medium for the exponential growth of
      Leuconostoc mesenteroides ATCC8293.
AB  - Leuconostoc mesenteroides is a heterofermentative Grampositive bacterium that
      plays key roles in fermentation of foods such as kimchi, sauerkraut, and milk,
      leading to the production of various organic acids and aromatic compounds. To
      study the microbiological and genomic characteristics of L. mesenteroides, we
      have developed a new chemically defined minimal medium by using the single
      omission technique. During the exponential cell growth, this species required
      glutamine, methionine, valine, and nicotinic acid as essential nutrients and 8
      amino acids (arginine, cysteine, histidine, leucine, phenylalanine, proline,
      threonine, and tryptophan), 5 vitamins (ascorbic acid, folic acid, inosine,
      calcium panthothenate, and thiamine), and others (manganese, magnesium, adenine,
      uracil, and Tween 80) as supplemental nutrients. This medium is useful to study
      the metabolic characteristics of L. mesenteroides and to explain its role in food
      fermentation.

PMID- 23124344
TI  - Mass spectrometry-based metabolite profiling and bacterial diversity
      characterization of Korean traditional meju during fermentation.
AB  - The metabolite profile of meju during fermentation was analyzed using mass
      spectrometry techniques, including GC-MS and LC-MS, and the bacterial diversity
      was characterized. The relative proportions of bacterial strains indicated that
      lactic acid bacteria, such as Enterococcus faecium and Leuconostoc lactis, were
      the dominant species. In partial least-squares discriminate analysis (PLS-DA),
      the componential changes, which depended on fermentation, proceeded gradually in
      both the GC-MS and LC-MS data sets. During fermentation, lactic acid, amino
      acids, monosaccharides, sugar alcohols, and isoflavonoid aglycones (daidzein and
      genistein) increased, whereas citric acid, glucosides, and disaccharides
      decreased. MS-based metabolite profiling and bacterial diversity characterization
      of meju demonstrated the changes in metabolites according to the fermentation
      period and provided a better understanding of the correlation between metabolites
      and bacterial diversity.

PMID- 23124345
TI  - Cloning, heterologous expression, and characterization of novel protease
      resistant alpha-galactosidase from new Sphingomonas strain.
AB  - The alpha-galactosidase-coding gene agaAJB13 was cloned from Sphingomonas sp.
      JB13 showing 16S rDNA (1,343 bp) identities of < or =97.2% with other identified
      Sphingomonas strains. agaAJB13 (2,217 bp; 64.9% GC content) encodes a 738-residue
      polypeptide (AgaAJB13) with a calculated mass of 82.3 kDa. AgaAJB13 showed the
      highest identity of 61.4% with the putative glycosyl hydrolase family 36 alpha
      galactosidase from Granulicella mallensis MP5ACTX8 (EFI56085). AgaAJB13 also
      showed <37% identities with reported protease-resistant or Sphingomonas alpha
      galactosidases. A sequence analysis revealed different catalytic motifs between
      reported Sphingomonas alpha-galactosidases (KXD and RXXXD) and AgaAJB13 (KWD and
      SDXXDXXXR). Recombinant AgaAJB13 (rAgaAJB13) was expressed in Escherichia coli
      BL21 (DE3). The purified rAgaAJB13 was characterized using p-nitrophenyl-alpha-D
      galactopyranoside as the substrate and showed an apparent optimum at pH 5.0 and
      60 degrees C and strong resistance to trypsin and proteinase K digestion.
      Compared with reported proteaseresistant alpha-galactosidases showing
      thermolability at 50 degrees C or 60 degrees C and specific activities of <71
      U/mg with or without protease treatments, rAgaAJB13 exhibited a better thermal
      stability (half-life of >60 min at 60 degrees C) and higher specific activities
      (225.0-256.5 U/mg). These sequence and enzymatic properties suggest AgaAJB13 is
      the first identified and characterized Sphingomonas alpha-galactosidase, and
      shows novel protease resistance with a potential value for basic research and
      industrial applications.

PMID- 23124346
TI  - Kinetic properties of manganese peroxidase from the mushroom Stereum ostrea and
      its ability to decolorize dyes.
AB  - Manganese peroxidase (MnP) was isolated from the culture filtrate of the wood log
      mushroom Stereum ostrea (S. ostrea), grown on Koroljova medium, and then purified
      by ammonium sulfate [70% (w/v)] fractionation, DEAE-cellulose anion exchange
      chromatography, and Sephadex G-100 column chromatography, with an attainment of
      88.6-fold purification and the recovery of 22.8% of initial activity. According
      to SDS-PAGE the molecular mass of the MnP was 40 kDa. The optimal pH and
      temperature were found to be 4.5 and 35 degrees C, respectively. The enzyme was
      stable even after exposure to a pH range of 4.5 to 6.0, and at temperatures of up
      to 35 degrees C at a pH of 4.5 for 1h. The K(m) and V(max) values for the
      substrate phenol red were found to be 8 micronm and 111.14 U/mg of protein,
      respectively. The MnP also oxidized other substrates such as guaiacol, DMP, and
      veratryl alcohol. Sodium azide, EDTA, SDS, Cu(2+), and Fe(2+), at 1-5 mM,
      strongly inhibited enzyme activity, whereas Ca(2+) and Zn(2+) increased enzyme
      activity. The participation of the purified enzyme in the decolorization of dyes
      suggests that S. ostrea manganese peroxidase could be effectively employed in
      textile industries.

PMID- 23124348
TI  - Glutathione reductase from Oryza sativa increases acquired tolerance to abiotic
      stresses in a genetically modified Saccharomyces cerevisiae strain.
AB  - Glutathione reductase (GR, E.C. 1.6.4.2) is an important enzyme that reduces
      glutathione disulfide (GSSG) to a sulfydryl form (GSH) in the presence of an
      NADPH-dependent system. This is a critical antioxidant mechanism. Owing to the
      significance of GR, this enzyme has been examined in a number of animals, plants,
      and microbes. We performed a study to evaluate the molecular properties of GR
      (OsGR) from rice (Oryza sativa). To determine whether heterologous expression of
      OsGR can reduce the deleterious effects of unfavorable abiotic conditions, we
      constructed a transgenic Saccharomyces cerevisiae strain expressing the GR gene
      cloned into the yeast expression vector p426GPD. OsGR expression was confirmed by
      a semiquantitative reverse transcriptase polymerase chain reaction
      (semiquantitative RT-PCR) assay, Western-blotting, and a test for enzyme
      activity. OsGR expression increased the ability of the yeast cells to adapt and
      recover from H2O2-induced oxidative stress and various stimuli including heat
      shock and exposure to menadione, heavy metals (iron, zinc, copper, and cadmium),
      sodium dodecyl sulfate (SDS), ethanol, and sulfuric acid. However, augmented OsGR
      expression did not affect the yeast fermentation capacity owing to reduction of
      OsGR by multiple factors produced during the fermentation process. These results
      suggest that ectopic OsGR expression conferred acquired tolerance by improving
      cellular homeostasis and resistance against different stresses in the genetically
      modified yeast strain, but did not affect fermentation ability.

PMID- 23124349
TI  - Application of Bacillus subtilis 168 as a multifunctional agent for improvement
      of the durability of cement mortar.
AB  - Microbiological calcium carbonate precipitation (MCCP) has been investigated for
      its ability to improve the durability of cement mortar. However, very few strains
      have been applied to crack remediation and strengthening of cementitious
      materials. In this study, we report the biodeposition of Bacillus subtilis 168
      and its ability to enhance the durability of cement material. B. subtilis 168 was
      applied to the surface of cement specimens. The results showed a new layer of
      deposited organic-inorganic composites on the surface of the cement paste. In
      addition, the water permeability of the cement paste treated with B. subtilis 168
      was lower than that of non-treated specimens. Furthermore, artificial cracks in
      the cement paste were completely remediated by the biodeposition of B. subtilis
      168. The compressive strength of cement mortar treated with B. subtilis 168
      increased by about 19.5% when compared with samples completed with only B4
      medium. Taken together, these findings suggest that the biodeposition of B.
      subtilis 168 could be used as a sealing and coating agent to improve the strength
      and water resistance of concrete. This is the first paper to report the
      application of Bacillus subtilis 168 for its ability to improve the durability of
      cement mortar through calcium carbonate precipitation.

PMID- 23124347
TI  - Fungal diversity and plant growth promotion of endophytic fungi from six
      halophytes in Suncheon Bay.
AB  - Endophytic fungi were isolated from roots of six halophytes in Suncheon Bay. The
      endophytic fungi of 35 species isolated from halophytes were identified by
      internal transcribed spacer (ITS) containing the ITS1, 5.8s, and ITS2 regions.
      All fungal strains were analyzed to diversity at the genus level. Fungal culture
      filtrates (FCF) of endophytic fungi were treated to Waito-c rice (WR) seedling
      for plant growth-promoting verification. It was confirmed that fungal strain Sj-2
      2 provided plant growth promotion (PGP) to WR seedling. Then, PGP of Suaeda
      japonica was confirmed by treating culture filtrate of Sj-2-2. As a result, it
      was verified that culture filtrate of Sj-2-2 had more advanced PGP than positive
      control when treated to S. japonica. The secondary metabolites involved in
      culture filtrate of Sj-2-2 were identified by HPLC and GC-MS SIM analysis. The
      presence of physiologically bioactive gibberellins (GAs) and other inactive GAs
      in culture filtrate of Sj-2-2 was detected. The molecular analysis of sequences
      of Sj-2-2 showed the similarity to Penicillium sp. of 99% homology. The PGP of Sj
      2-2 as well as symbiosis between endophytic fungi and halophytes growing
      naturally in salt marsh was confirmed. Sj-2-2 was identified as a new fungal
      strain producing GAs by molecular analysis of sequences. Consequently, the Sj-2-2
      fungal strain was named as Penicillium sp. Sj-2-2. In this study, the diversity
      of endophytic fungi isolated from roots of halophytes in salt marsh and the PGP
      of a new gibberellin-producing fungal strain were confirmed.

PMID- 23124350
TI  - Quantitative real-time PCR assay for detection of Paenibacillus polymyxa using
      membrane-fusion protein-based primers.
AB  - Paenibacillus polymyxa is known to be a plant-growthpromoting rhizobacterium. The
      present study describes a quantitative polymerase chain reaction (qPCR) assay for
      the specific detection and quantitation of P. polymyxa using a primer pair based
      on the sequence of a membranefusion protein for the amplification of a 268 bp DNA
      fragment. This study reports that the qPCR-based method is applicable for the
      rapid and sensitive detection of P. polymyxa and can be used as an alternative
      method for agricultural soil monitoring.

PMID- 23124351
TI  - Protective immunity of Pichia pastoris-expressed recombinant envelope protein of
      Japanese encephalitis virus.
AB  - Japanese encephalitis virus (JEV) envelope (E) protein holds great promise for
      use in the development of a recombinant vaccine. Purified recombinant E (rE)
      protein may be useful for numerous clinical applications; however, there are
      limitations in using the Escherichia coli expression system for producing high
      quality rE protein. Therefore, in this study, the yeast expression system was
      used to generate the rE protein. For protein production using the yeast system,
      the full-length JEV E gene was cloned into Pichia pastoris. SDS-PAGE and
      immunoblotting analysis demonstrated that the rE protein had a molecular mass of
      58 kDa and was glycosylated. The predicted size of the mature unmodified E
      protein is 53 kDa, suggesting that post-translational modifications resulted in
      the higher molecular mass. The rE protein was purified to greater than 95% purity
      using combined ammonium sulfate precipitation and a SP-Sepharose Fast Flow
      column. This purified rE protein was evaluated for immunogenicity and protective
      efficacy in mice. The survival rates of mice immunized with the rE protein were
      significantly increased over that of Hyphantria cunea nuclear polyhedrosis virus
      E protein (HcE). Our results indicate that the rE protein expressed in the P.
      pastoris expression system holds great promise for use in the development of a
      subunit vaccine against JEV.

PMID- 23124352
TI  - Characterization and cDNA cloning of a defensin-like peptide, harmoniasin, from
      Harmonia axyridis.
AB  - We compared the mRNA expression profile of the Harmonia axyridis larvae that were
      either untreated or treated with LPS. The extracted mRNAs were subjected to ACP
      RTPCR analysis using a combination of arbitrary primers and oligo (dT) primer.
      Among the 47 DEGs differentially expressed, we identified a cDNA showing homology
      with defensin-like antibacterial peptide. The cDNA showed a putative 32-residue
      signal sequence and a 50-residue mature peptide named harmoniasin. We also
      investigated the antibacterial activity of the harmoniasin analog, which
      exhibited potent antibacterial activities against Gramnegative and -positive
      bacteria strains and it also evidenced no hemolytic activity.

PMID- 23124353
TI  - HY251, a novel decahydrocyclopenta[a]indene analog, induces apoptosis via tBid
      mediated intrinsic pathway in human ovarian cancer PA-1 cells.
AB  - We previously isolated a novel compound, HY251, with the molecular structure of 3
      propyl-2-vinyl-1,2,3,3a,3b,6,7,7a,8,8adecahydrocyclopenta[ a]indene-3,3a,7a,8a
      tetraol from the roots of Aralia continentalis. The current study was designed to
      evaluate the detailed molecular mechanisms underlying the apoptotic induction by
      HY251 in human ovarian cancer PA-1 cells. TUNEL assay and Western blot analyses
      revealed an appreciable apoptotic induction in PA-1 cells treated with 60 MUM of
      HY251 for 24 h. This apoptotic induction was associated with caspase-8-dependent
      Bid cleavage, which in turn resulted in the formation of pro-apoptotic truncated
      Bid (tBid), and activation of caspase-9 and -3, as well as the cleavage of
      poly(ADP-ribose) polymerase (PARP). Moreover, we found that this death event was
      also associated with the significant upregulation and activation of the p53 tumor
      suppressor protein through phosphorylation at Ser15. Therefore, we suggest that
      HY251 may be a potent cancer chemotherapeutic candidate for the treatment of
      ovarian cancer.

PMID- 23124354
TI  - Inhibition of Leydig tumor growth by farnesoid X receptor activation: the in
      vitro and in vivo basis for a novel therapeutic strategy.
AB  - Leydig cell tumors (LCTs) are the most common tumors of the gonadal stroma and
      represent about 3% of all testicular neoplasms. In most cases, LCTs are benign;
      however, if the tumor is malignant, no effective treatments are currently
      available. We have recently reported that farnesoid X receptor (FXR) is expressed
      in R2C Leydig tumor cells, and it reduces the estrogen-dependent cell
      proliferation by negatively regulating aromatase expression. Here, we
      demonstrated that treatment with GW4064, a specific FXR agonist, markedly reduced
      Leydig tumor growth in vivo by inhibiting proliferation and inducing apoptosis.
      Indeed, the tumors from GW4064-treated mice exhibited a decrease in the
      expression of the proliferation marker Ki-67 and aromatase along with an increase
      in the apoptotic nuclei. FXR activation induced an enhanced poly(ADP-ribose)
      polymerase cleavage, a marked DNA fragmentation and a strong increase in TUNEL
      positive R2C cells also in vitro. Moreover, in both in vivo and in vitro models,
      FXR ligands upregulated mRNA and protein levels of p53 and of its downstream
      effector p21(WAF1/Cip1) . Functional experiments showed that FXR ligands
      upregulated p53 promoter activity and this occurred through an increased binding
      of FXR/nuclear factor-kB (NF-kB) complex to the NF-kB site located within p53
      promoter region as revealed by electrophoretic mobility shift assay and chromatin
      immunoprecipitation analysis. Taken together, results from our study show, for
      the first time, that treatment with FXR ligands induces Leydig tumor regression
      in vivo, suggesting that activation of FXR may represent a promising therapeutic
      strategy for LCTs.

PMID- 23124356
TI  - Association of myeloperoxidase gene variation with carotid atherosclerosis in
      patients with essential hypertension.
AB  - The aim of this study was to investigate the association between myeloperoxidase
      (MPO) gene polymorphisms and carotid atherosclerosis (AS) in patients with
      essential hypertension (EH). A total of 214 patients with EH were divided into an
      AS and a non-atherosclerosis (non-AS) group. MPO gene polymorphisms in EH were
      detected using PCR. The frequency of increased intima-media thickness and the
      occurrence of plaque in the carotid artery in the AS group was higher compared to
      the non-AS group. The frequency of the GC genotype in the AS group was
      significantly higher compared to the non-AS group. The frequency of carotid AS is
      higher in patients with hypertension, which is related to the MPO gene
      polymorphism. 

PMID- 23124355
TI  - Proximal tubular cells contain a phenotypically distinct, scattered cell
      population involved in tubular regeneration.
AB  - Regeneration of injured tubular cells occurs after acute tubular necrosis
      primarily from intrinsic renal cells. This may occur from a pre-existing
      intratubular stem/progenitor cell population or from any surviving proximal
      tubular cell. In this study, we characterize a CD24-, CD133-, and vimentin
      positive subpopulation of cells scattered throughout the proximal tubule in
      normal human kidney. Compared to adjacent 'normal' proximal tubular cells, these
      CD24-positive cells contained less cytoplasm, fewer mitochondria, and no brush
      border. In addition, 49 marker proteins are described that are expressed within
      the proximal tubules in a similar scattered pattern. For eight of these markers,
      we confirmed co-localization with CD24. In human biopsies of patients with acute
      tubular necrosis (ATN), the number of CD24-positive tubular cells was increased.
      In both normal human kidneys and the ATN biopsies, around 85% of proliferating
      cells were CD24-positive - indicating that this cell population participates in
      tubular regeneration. In healthy rat kidneys, the novel cell subpopulation was
      absent. However, upon unilateral ureteral obstruction (UUO), the novel cell
      population was detected in significant amounts in the injured kidney. In summary,
      in human renal biopsies, the CD24-positive cells represent tubular cells with a
      deviant phenotype, characterized by a distinct morphology and marker expression.
      After acute tubular injury, these cells become more numerous. In healthy rat
      kidneys, these cells are not detectable, whereas after UUO, they appeared de novo
      - arguing against the notion that these cells represent a pre-existing progenitor
      cell population. Our data indicate rather that these cells represent transiently
      dedifferentiated tubular cells involved in regeneration.

PMID- 23124357
TI  - The challenges presented by decomposition.

PMID- 23124358
TI  - Perception of pointing from biological motion point-light displays in typically
      developing children and children with autism spectrum disorder.
AB  - We examined whether the movement involved in a pointing gesture, depicted using
      point-light displays, is sufficient to cue attention in typically developing
      children (TD) and children with autism spectrum disorder (ASD) (aged 8-11 years).
      Using a Posner-type paradigm, a centrally located display indicated the location
      of a forthcoming target on 80% of trials and the opposite location on 20% of
      trials. TD children, but not children with ASD, were faster to identify a validly
      cued target than an invalidly cued target. A scrambled version of the point-light
      pointing gesture, retaining individual dot speed and direction of movement but
      not the configuration, produced no validity effect in either group. A video of a
      pointing gesture produced validity effects in both groups.

PMID- 23124359
TI  - Fatigue, stress and coping in mothers of children with an autism spectrum
      disorder.
AB  - Raising a child with an autism spectrum disorder (ASD) can be exhausting, which
      has the potential to impact on parental health and wellbeing. The current study
      investigated the influence of maternal fatigue and coping on the relationship
      between children's problematic behaviours and maternal stress for 65 mothers of
      young children (aged 2-5 years) with ASDs. Results showed that maternal fatigue
      but not maladaptive coping mediated the relationship between problematic child
      behaviours and maternal stress. These findings suggest child behaviour
      difficulties may contribute to parental fatigue, which in turn may influence use
      of ineffective coping strategies and increased stress. The significance of
      fatigue on maternal wellbeing was highlighted as an important area for
      consideration in families of children with an ASD.

PMID- 23124360
TI  - Orienting in response to gaze and the social use of gaze among children with
      autism spectrum disorder.
AB  - Potential relations between gaze cueing, social use of gaze, and ability to
      follow line of sight were examined in children with autism and typically
      developing peers. Children with autism (mean age = 10 years) demonstrated intact
      gaze cueing. However, they preferred to follow arrows instead of eyes to infer
      mental state, and showed decreased accuracy in following line of sight when
      several visual distracters were present. Performance across tasks was not
      correlated for either group. Findings suggest that children with autism are less
      inclined to prioritize and select eyes, particularly in visually-rich
      environments. Gaze-following deficits may lie at the level of selective
      attention, rather than cueing-a possibility that can be explored with more
      complex and ecologically valid tasks.

PMID- 23124362
TI  - Thermodynamic properties and structure of gaseous BMoO4.
AB  - The stability of gaseous BMoO(4) was confirmed by Knudsen effusion mass
      spectrometry. The gas-phase reaction involving B(2)O(3), MoO(2), MoO(3) and
      BMoO(4) was studied. On the basis of the equilibrium constants, the standard
      formation and atomization enthalpies of gaseous BMoO(4) (-744.1 +/- 24 kJ mol(-1)
      and 2963 +/- 25 kJ mol(-1), respectively) at 298 K were determined. To obtain the
      structure parameters and vibrational frequencies of gaseous BMoO(4), a quantum
      chemical investigation of this molecule was undertaken. Based on the critical
      analysis of the literature data concerning the standard formation enthalpies of
      gaseous BWO(4), BPO(4) and BPO(3), we adopted new values for Delta(f)H(0)(298)
      which are equal (-934.4 +/- 29.3 kJ mol(-1), -975.8 +/- 16.2 kJ mol(-1) and 
      717.0 +/- 19.3 kJ mol(-1)), respectively.

PMID- 23124361
TI  - Brief report: Predictors of outcomes in the Early Start Denver Model delivered in
      a group setting.
AB  - There is a paucity of studies that have looked at factors associated with
      responsiveness to interventions in preschoolers with autism spectrum disorder
      (ASD). We investigated learning profiles associated with response to the early
      start Denver model delivered in a group setting. Our preliminary results from 21
      preschool children with an ASD aged 2- to 5-years suggest that the children with
      more advanced skills in functional use of objects, goal understanding and
      imitation made the best developmental gains after 1 year of treatment. Cognitive
      abilities, social attention, intensity of the treatment and chronological age
      were not associated with treatment gains.

PMID- 23124363
TI  - Optimized signal peptides for the development of high expressing CHO cell lines.
AB  - Recombinant biotherapeutic proteins such as monoclonal antibodies are mostly
      produced in Chinese hamster ovary (CHO) cells and pharmaceutical companies are
      interested in an appropriate platform technology for the development of large
      scale production processes. A major aim of our study was therefore to improve the
      secretion efficiency of a recombinant biotherapeutic antibody by optimizing
      signal peptides. Reporter molecules such as gaussia and vargula luciferase or
      secreted alkaline phosphatase are frequently used to this end. In striking
      contrast, we used a biotherapeutic antibody that was fused to 16 different signal
      peptides during our study. In this way, the secretion efficiency of the
      recombinant antibody has been analyzed by transient expression experiments in CHO
      cell lines. Compared to the control signal peptide, it was not possible to
      achieve higher efficiencies with signal peptides derived from a variety of
      species or even natural immunoglobulin G signal peptides. The best results were
      obtained with natural signal peptides derived from human albumin and human
      azurocidin. These results were confirmed by fed-batch experiments with stably
      transfected cell pools, in which cell-specific productivities up to 90 pg cell(
      1) day(-1) and product concentrations up to 4 g L(-1) could be determined using
      the albumin signal peptide. Finally, the applicability of the identified signal
      peptides for both different antibodies and non-antibody products was demonstrated
      by transient expression experiments. In conclusion, it was found that signal
      peptides derived from human albumin and human azurocidin are most appropriate to
      generate cell lines with clearly improved production rates suitable for
      commercial purposes in a product-independent manner.

PMID- 23124364
TI  - Disseminated zygomycosis caused by Cunninghamella bertholletiae in patient with
      hematological malignancy and review of published case reports.
AB  - Cunninghamella bertholletiae is an unusual opportunistic pathogen belonging to
      the class Zygomycetes, order Mucorales, and the family Cunninghamellaceae. It has
      been identified with increased frequency in immunocompromised patients,
      especially those with hematological malignancy. Clinical infection by this fungus
      is almost always devastating. We report a fatal case of disseminated zygomycosis
      due to Cunninghamella bertholletiae in an acute myeloid leukemia patient without
      chemotherapy. We also reviewed the cases of Cunninghamella bertholletiae
      infection reported in these 20 years. These cases highlight the high mortality
      rate and rapid progression associated with this opportunistic fungal infection in
      immunocompromised patients.

PMID- 23124366
TI  - Whistleblowing.

PMID- 23124367
TI  - Hip examination.

PMID- 23124368
TI  - Compartment syndrome of the lower limb: how to  diagnose it, assess it and not to
      miss it.

PMID- 23124365
TI  - TDP-43 skeins show properties of amyloid in a subset of ALS cases.
AB  - Aggregation of TDP-43 proteins to form intracellular inclusions is the primary
      pathology in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar
      degeneration (FTLD) with TDP-43 inclusions (FTLD-TDP). Histologically, in the
      cerebral cortex and limbic regions of affected ALS and FTLD-TDP patients, these
      pathologies occur as a variety of cytoplasmic, neuritic and intranuclear TDP-43
      inclusions. In the spinal cord and lower brainstem of ALS patients, the lesions
      form cytoplasmic dashes or complex filamentous and spherical profiles in addition
      to skein-like inclusions (SLI). Ultrastructurally, the morphology of TDP-43
      inclusions is heterogeneous but mainly composed of loose bundles of 10- to 20-nm
      diameter straight filaments associated with electron-dense granular material. All
      of these TDP-43 inclusions are generally described as disordered amorphous
      aggregations unlike the amyloid fibrils that characterize protein accumulations
      in neurodegenerative diseases such as Alzheimer's disease and Parkinson's
      disease. We here report that Thioflavin-S positive SLI are present in a subset of
      ALS cases, while TDP-43 inclusions outside the spinal cord lack the chemical
      properties of amyloid. Further, we examine the differential enrichment of
      fibrillar profiles in SLI of ALS cases by TDP-43 immuno-electron microscopy
      (immuno-EM). The demonstration that pathological TDP-43 can be amyloidogenic in
      situ suggests the following conclusions: (1) the conformational changes
      associated with TDP-43 aggregation are more complex than previously thought; (2)
      Thioflavin-S positive SLI may be composed primarily of filamentous
      ultrastructures.

PMID- 23124369
TI  - Operative management of hip fractures:  a review of the NICE guidelines.

PMID- 23124370
TI  - Reshuffle kerfuffle?

PMID- 23124371
TI  - Managing a venous leg ulcer in the 21st century, by improving self-care.
AB  - This paper examines the context of managing a long-term condition within the
      community environment using appropriate evidence-based literature. It is a case
      study that focuses upon concordance with compression bandaging in treating venous
      leg ulceration and preventing ulcer recurrence through a well leg clinic. The
      challenges of this episode of care and the interventions put in place to improve
      concordance and promote self-care will be explained and analysed.

PMID- 23124373
TI  - Is there room at the inn? Palliative care for the homeless.

PMID- 23124372
TI  - Providing holistic support for patients with inflammatory bowel disease.
AB  - Inflammatory bowel diseases such as ulcerative colitis and Crohn's disease are
      life-long, complex conditions. They are characterised by periods of exacerbation
      and remission and surgical intervention may be required in severe cases. Drugs
      employed in the management of IBD are used to induce remission and maintain
      remission. IBD has a physical, psychological and sociological impact on
      individuals and IBD quality standards have been developed to provide a framework
      for addressing the services and care that should be available for them.
      Complementary and alternative medicine (CAM) therapies play an important role in
      the holistic approach to management of IBD as they are being increasingly used
      alongside conventional medical treatments. Community nurses have an important
      role to play in the management and care of individuals with IBD and in supporting
      them in making informed and appropriate choices that support their wellbeing and
      quality of life.

PMID- 23124374
TI  - Intravenous therapy: guidance on devices, management and care.
AB  - This article aims to provide guidance for practitioners on intravenous therapy
      devices, their management and care. It explains the indications for their use and
      considerations when selecting devices for intravenous therapy and treatment.  
      Both PVADs and CVADs are discussed in detail to provide the practitioner with a
      clear understanding for each. Infection control and how to reduce infection risks
      are also addressed with recommendations for best practice guidance on flushing
      devices, minimising complications and documentation.   This article addresses the
      importance of safe practice and aims to help practitioners to improve their
      knowledge and clinical decision-making for patients undergoing intravenous
      therapy.

PMID- 23124375
TI  - More than a sum of parts.

PMID- 23124376
TI  - Research to support evidence-based practice in COPD community nursing.
AB  - Evidence-based practice (EBP) is a requirement of nurses through the generation
      of evidence to implementing it, in a bid to to improve clinical practice.
      However, EBP is difficult to achieve. This paper highlights an approach to
      generating evidence for enhancing community nursing services for patients with
      chronic obstructive pulmonary disease (COPD) through a collaborative partnership.
      A district nurse and two nursing lecturers formed a partnership to devise a
      systematic review protocol and perform a systematic review to enhance COPD
      practice.  This paper illustrates the Joanna Briggs Institute (JBI) systematic
      review process, the review outcomes and the practitioner learning. Collaborative
      partnerships between academics, researchers and clinicians are a potentially
      useful model to facilitate enhanced outcomes in evidence-based practice and
      evidence application.

PMID- 23124377
TI  - Community matron caseload numbers: a literature review.
AB  - In early 2005, the Department of Health published its strategy for addressing the
      health and social care needs of people with long-term conditions (2005a; b).
      Community matrons were recruited to deliver this strategy. Since this time, there
      has been some debate around the optimum caseload number for community matrons to
      function effectively (Abell et al, 2010). One study by Sargent et al (2008)
      concluded that community matrons were struggling to achieve and maintain 50
      patients on their caseload, due to nine areas that impact on caseload
      manageability. This literature review concluded there is a wide variation
      regarding the optimum caseload number ranging from 14 patients in intensive case
      management to 80-100 families per full-time health visitor. A number of authors
      do not specify caseload numbers due to the complexity of the task. However, what
      clearly emerges is that the factors that impact on case management appear to
      correlate with the issues identified by Sargent et al (2008).

PMID- 23124378
TI  - The Bribery Act 2010: an overview for district nurses.
AB  - The Bribery Act 2010 has been in force for a little over a year and has already
      served to reinforce the need for NHS organisations to adopt a proactive approach
      to preventing any suggestion that their staff are accepting inducements, in the
      form of gifts or hospitality, that could influence their performance. The robust
      policies on the acceptance of gifts and hospitality demanded by the 2010 Act
      require district nurses to be very cautious when offered a gift by a patient or
      commercial organisation. This article considers the implications of the Bribery
      Act 2010 on district nurse practice and the implications of failing to meet its
      provisions.

PMID- 23124379
TI  - Overflowing hospitals...

PMID- 23124380
TI  - Differentiating literacy growth of ELL students with LD from other high-risk
      subgroups and general education peers: evidence from grades 3-10.
AB  - The authors used a large data set (N = 1,011,549) to examine literacy growth over
      a single school year comparing general education (GenEd) students to three high
      risk subgroups: English language learners (ELL), those with a specific learning
      disability (LD), and those identified as both LD and ELL (LD-ELL) in students in
      Grades 3-10. The authors were particularly interested in whether variability
      existed between initial status and the growth trajectories of the three high-risk
      groups on measures of spelling, fluency, and reading comprehension across the
      school year and whether this variability was differentiated because of
      socioeconomic status (SES) as defined by free and reduced lunch (FRL) status.
      Results indicate that all high-risk groups began the year at substantially lower
      levels than their GenEd peers, with the largest differences seen between the LD
      ELL students and the other subgroups. Further results suggest that students who
      are in the high-risk subgroups and also qualify for FRL perform significantly
      worse than their peers in similar risk status groups who do not qualify for FRL,
      demonstrating the significant impact of SES on academic outcomes for all groups. 

PMID- 23124382
TI  - H(2)S inhibits oscillatory shear stress-induced monocyte binding to endothelial
      cells via nitric oxide production.
AB  - H(2)S is a signaling molecule associated with protection against vascular
      diseases, including atherosclerosis. This protection involves the stimulation of
      vasorelaxation, but other possible contributing mechanisms have not been
      extensively explored. In this study, we found that the vascular H(2)S-producing
      enzyme, cystathionine-gamma-lyase (CSE), was down-regulated by oscillatory shear
      stress (OSS) among various vaso-regulators. Consistently, NaHS, an H(2)S donor,
      appeared to inhibit OSS-induced THP-1 cell adhesion. We also found that NaHS
      activated the nitric oxide (NO)-producing Akt/endothelial nitric oxide synthase
      (eNOS) signaling pathway in response to OSS, whereas NaHS had no effect on
      IkappaB, a well-known molecule regulating pro-inflammatory signaling pathways.
      Moreover, NaHS increased OSS-dependent eNOS expression and decreased expression
      of intercellular adhesion molecule-1 (ICAM-1). NG-nitro-L-arginine methyl ester
      (L-NAME), an eNOS inhibitor, abrogated the inhibitory effects of NaHS on
      OSSinduced endothelial ICAM-1 expression and monocyte adhesion to endothelial
      cells. These data suggest that down-regulation of CSE resulting in decreased
      levels of H(2)S is a key factor for OSS-associated atherogenesis and further
      suggest that regulation of H(2)S production can be a potential target for
      preventing cardiovascular diseases.

PMID- 23124384
TI  - Improve photo-electron conversion efficiency of ZnO/CdS coaxial nanorods by p
      type CdTe coating.
AB  - Coaxial nanorods with a single-crystalline core and nanocrystal sensitizer shell
      are a promising nanostructure to enhance the performance of semiconductor
      sensitized solar cells. Herein, we report the fabrication of coaxial nanorods by
      depositing n-type CdS and p-type CdTe nanocrystals sequentially on ZnO nanorods.
      We find that p-type CdTe nanocrystals can work jointly with n-type CdS
      nanocrystals to enhance the photocurrent and voltage, achieving a conversion
      efficiency more than three times that of pure ZnO/CdS nanorods. Electrochemical
      impedance spectroscopy characterization suggests that the stepwise band structure
      of ZnO/CdS/CdTe is conducive to improving charge separation and extending the
      electron diffusion length, finally contributing to a high conversion efficiency.

PMID- 23124381
TI  - Reactivity to stress and the cognitive components of math disability in grade 1
      children.
AB  - This study investigated the relationship among working memory, processing speed,
      math performance, and reactivity to stress in 83 Grade 1 children. Specifically,
      39 children with math disability (MD) were compared to 44 children who are
      typically achieving (TA) in mathematics. It is the first study to use a
      physiological index of stress (salivary cortisol levels) to measure children's
      reactivity while completing tasks that assess the core components of MD: working
      memory for numbers, working memory for words, digits backward, letter number
      sequence, digit span forward, processing speed for numbers and words, block
      rotation, and math tasks. Grade 1 children with MD obtained significantly lower
      scores on the letter number sequence and quantitative concepts tasks. Higher
      levels of reactivity significantly predicted poorer performance on the working
      memory for numbers, working memory for words, and quantitative concepts tasks for
      Grade 1 children, regardless of math ability. Grade 1 children with MD and higher
      reactivity had significantly lower scores on the letter number sequence task than
      the children with MD and low reactivity. The findings suggest that high
      reactivity impairs performance in working memory and math tasks in Grade 1
      children, and young children with high reactivity may benefit from interventions
      aimed at lowering anxiety in stressful situations, which may improve learning. 

PMID- 23124383
TI  - Constitutive expression of mammalian nitric oxide synthase in tobacco plants
      triggers disease resistance to pathogens.
AB  - Nitric oxide (NO) is known for its role in the activation of plant defense
      responses. To examine the involvement and mode of action of NO in plant defense
      responses, we introduced calmodulin-dependent mammalian neuronal nitric oxide
      synthase (nNOS), which controls the CaMV35S promoter, into wild-type and NahG
      tobacco plants. Constitutive expression of nNOS led to NO production and
      triggered spontaneous induction of leaf lesions. Transgenic plants accumulated
      high amounts of H(2)O(2), with catalase activity lower than that in the wild
      type. nNOS transgenic plants contained high levels of salicylic acid (SA), and
      they induced an array of SA-, jasmonic acid (JA)-, and/or ethylene (ET)-related
      genes. Consequently, NahG co-expression blocked the induction of systemic
      acquired resistance (SAR)-associated genes in transgenic plants, implying SA is
      involved in NO-mediated induction of SAR genes. The transgenic plants exhibited
      enhanced resistance to a spectrum of pathogens, including bacteria, fungi, and
      viruses. Our results suggest a highly ranked regulatory role for NO in SA-, JA-,
      and/or ET-dependent pathways that lead to disease resistance.

PMID- 23124385
TI  - The effect of individual differences in working memory capacity on sentence
      comprehension: an FMRI study.
AB  - This study explores the interaction between working memory systems and language
      processing by examining how differences in working memory capacity (WMC)
      modulates neural activation levels and functional connectivity during sentence
      comprehension. The results indicate that two working memory systems may be
      involved in sentence comprehension, the verbal working memory system and the
      episodic buffer, but during different phases of the task. A sub-region of the
      left inferior frontal gyrus (BA 45) was correlated with WMC during the probe and
      not during sentence reading while the only region to reveal a correlation with
      WMC during sentence reading was the posterior cingulate/precuneus area, a region
      linked to event representation. In addition, functional connectivity analysis
      suggests that there were two distinct networks affected by WMC. The first was a
      semantic network that included the middle temporal cortex, an anterior region of
      the inferior frontal gyrus and the inferior parietal region. The second included
      the posterior cingulate and BA 45 of the inferior frontal gyrus. We propose here
      that high capacity readers may generate an event representation of the sentence
      during reading that aids in comprehension and that this event representation
      involves the processing of the posterior cingulate cortex.

PMID- 23124386
TI  - Congenital atresia of the left main coronary artery with noncompaction of the
      ventricular myocardium in an asymptomatic young child.
AB  - Congenital atresia of the left main coronary artery (LMCA) is an extremely rare
      cardiac anomaly, and no cases have been reported from the mainland of China. The
      diagnosis for the 20-month-old boy in the reported case highlights the
      essentiality of comprehensive diagnostic measures. To avoid a misdiagnosis,
      electrocardiographic and echocardiographic evidence should be vigilantly explored
      in young children suspected of having dilated cardiomyopathy. This is the first
      case report of LMCA atresia associated with noncompaction of the left ventricular
      myocardium. 

PMID- 23124387
TI  - Response to intravenous potassium chloride supplementation in pediatric cardiac
      intensive care patients.
AB  - Potassium chloride (KCl) supplementation is common among critically ill children.
      Intravenous (IV) KCl supplementation for pediatric patients is poorly
      characterized. This study aimed to examine the efficacy and safety of IV KCL and
      to determine factors affecting patient responses to IV KCL in the pediatric
      cardiac intensive care unit (CICU). A retrospective review of 211 children (794
      KCl doses) undergoing cardiac surgery or a hospital stay for heart failure in the
      CICU of a tertiary care teaching and referral children's hospital in 2011 was
      performed. Demographic data, weight, height, creatinine, and concomitant
      medications during each KCl dose were recorded and analyzed. Body surface area
      (BSA), creatinine clearance, and change in [K(+)] were calculated. The median age
      of the children was 4 months (range, 10 days-18 years). In this study, 151 KCl
      doses were administered to neonates (19 %), 307 doses (39 %) to females, and 510
      doses (64 %) to patients with a BSA smaller than 0.33 m(2) (a group with relative
      renal insufficiency). The mean KCl dose was 0.97 +/- 0.006 mEq/kg. No adverse
      events were associated with IV KCl administration. Blood/plasma [K(+)] increased
      0.8 +/- 0.02 mEq/L. The responses to KCl did not differ significantly between
      males and females, between neonates and children, or between patients with a BSA
      smaller than 0.33 m(2) and those with a BSA of 0.33 m(2) or larger. The responses
      to IV KCl were attenuated by concomitant furosemide (p = 0.01), amphotericin B (p
      < 0.01), and KCl in parenteral nutrition (p < 0.01). The responses were augmented
      by concomitant enalapril (p = 0.03), ethacrynic acid (p < 0.001), and
      hemodialysis (p < 0.01). Intravenous KCl can be administered safely for CICU
      patients. Responses to KCl are altered when it is given with certain medications.
      Intravenous KCl should be used cautiously in children receiving angiotensin
      converting enzyme inhibitors. Future studies are needed for further
      characterization of factors affecting responses to IV KCl in children.

PMID- 23124388
TI  - Dexmedetomidine for patients undergoing diagnostic cardiac procedures: a
      noninferiority study.
AB  - When anesthetizing children with congenital heart disease for diagnostic cardiac
      catheterization, anesthesiologists and cardiologists seek to use anesthetic
      regimens that yield minimal hemodynamic changes and allow for spontaneous
      ventilations. Recently, dexmedetomidine has been used as an anesthesia adjunct
      because of its sedative and analgesic properties and minimal ventilatory
      depressive effects. We tested the hypothesis that the combination of sevoflurane
      and dexmedetomidine is non-inferior to sevoflurane alone as it refers to
      hemodynamic measurements during diagnostic cardiac catheterization in children
      with a transplanted heart, one ventricle (Fontan procedure), or normal cardiac
      physiology. Patients were anesthetized with inhalation of sevoflurane in nitrous
      oxide/oxygen and, after baseline hemodynamic measurements, successive boluses of
      dexmedetomidine followed by continuous infusion were administered. In this study,
      non-inferiority was shown when differences at steady-state (dexmedetomidine +
      sevoflurane) compared to baseline (sevoflurane alone) and its associated 95%
      confidence interval fell completely within the range of plus or minus 20%. Forty
      one (26 normal physiology, 9 cardiac transplantation, and 6 Fontan) patients were
      enrolled. Non-inferiority of sevoflurane + dexmedetomidine compared with
      sevoflurane alone was shown for heart rate, but not for arterial blood pressure
      in patients with normal and cardiac transplant physiology. In patients with
      normal cardiac physiology, non-inferiority was demonstrated for bispectral index.
      Therefore, while the lack of depressive respiratory effects and non-inferiority
      for heart rate are desirable, the lack of non-inferiority of dexmedetomidine +
      sevoflurane combination for arterial blood pressure do not justify the routine
      use of this combination compared with sevoflurane alone for children with
      congenital heart disease undergoing cardiac catheterization.

PMID- 23124389
TI  - A high-throughput SNP marker system for parental polymorphism screening, and
      diversity analysis in common bean (Phaseolus vulgaris L.).
AB  - Single nucleotide polymorphism (SNP) detection has become a marker system of
      choice, because of the high abundance of source polymorphisms and the ease with
      which allele calls are automated. Various technologies exist for the evaluation
      of SNP loci and previously we validated two medium throughput technologies. In
      this study, our goal was to utilize a 768 feature, Illumina GoldenGate assay for
      common bean (Phaseolus vulgaris L.) developed from conserved legume gene
      sequences and to use the new technology for (1) the evaluation of parental
      polymorphisms in a mini-core set of common bean accessions and (2) the analysis
      of genetic diversity in the crop. A total of 736 SNPs were scored on 236 diverse
      common bean genotypes with the GoldenGate array. Missing data and heterozygosity
      levels were low and 94 % of the SNPs were scorable. With the evaluation of the
      parental polymorphism genotypes, we estimated the utility of the SNP markers in
      mapping for inter-genepool and intra-genepool populations, the latter being of
      lower polymorphism than the former. When we performed the diversity analysis with
      the diverse genotypes, we found Illumina GoldenGate SNPs to provide equivalent
      evaluations as previous gene-based SNP markers, but less fine-distinctions than
      with previous microsatellite marker analysis. We did find, however, that the gene
      based SNPs in the GoldenGate array had some utility in race structure analysis
      despite the low polymorphism. Furthermore the SNPs detected high heterozygosity
      in wild accessions which was probably a reflection of ascertainment bias. The
      Illumina SNPs were shown to be effective in distinguishing between the genepools,
      and therefore were most useful in saturation of inter-genepool genetic maps. The
      implications of these results for breeding in common bean are discussed as well
      as the advantages and disadvantages of the GoldenGate system for SNP detection.

PMID- 23124390
TI  - Induced mutation in beta-CAROTENE HYDROXYLASE results in accumulation of beta
      carotene and conversion of red to orange color in pepper fruit.
AB  - Pepper fruit is typically red, but green, orange and yellow cultivars are gaining
      consumer acceptance. This color variation is mainly due to variations in
      carotenoid composition. Orange color in pepper can result from a number of
      carotenoid profiles, but its genetic basis is only partly known. We identified an
      EMS-induced orange-fruited mutant using the wild-type blocky red-fruited cultivar
      'Maor' as progenitor. This mutant accumulates mainly beta-carotene in its fruit,
      instead of the complex pattern of red and yellow carotenoids in 'Maor'. We
      identified an A(709) to G transition in the cDNA of beta-CAROTENE HYDROXYLASE2 in
      the orange pepper and complete co-segregation of this single-nucleotide
      polymorphism with the mutated phenotype. We therefore hypothesized that beta
      CAROTENE HYDROXYLASE2 controls the orange mutation in pepper. Interestingly, the
      expression of beta-CAROTENE HYDROXYLASE2 and additional carotenogenesis genes was
      elevated in the orange fruit compared with the red fruit, indicating possible
      feedback regulation of genes in the pathway. Because carotenoids serve as
      precursors for volatile compounds, we compared the volatile profiles of the two
      parents. The orange pepper contained more volatile compounds than 'Maor', with
      predominant elevation of norisoprenoids derived from beta-carotene degradation,
      while sesquiterpenes predominated in the red fruit. Because of the importance of
      beta-carotene as a provitamin A precursor in the human diet, the orange-fruited
      mutant might serve as a natural source for pepper fruit biofortification.
      Moreover, the change in volatile profile may result in a fruit flavor that
      differs from other pepper cultivars.

PMID- 23124391
TI  - Haplotype diversity and population structure in cultivated and wild barley
      evaluated for Fusarium head blight responses.
AB  - Fusarium head blight (FHB) is a threat to barley (Hordeum vulgare L.) production
      in many parts of the world. A number of barley accessions with partial resistance
      have been reported and used in mapping experiments to identify quantitative trait
      loci (QTL) associated with FHB resistance. Here, we present a set of barley
      germplasm that exhibits FHB resistance identified through screening a global
      collection of 23,255 wild (Hordeum vulgare ssp. spontaneum) and cultivated
      (Hordeum vulgare ssp. vulgare) accessions. Seventy-eight accessions were
      classified as resistant or moderately resistant. The collection of FHB resistant
      accessions consists of 5, 27, 46 of winter, wild and spring barley, respectively.
      The population structure and genetic relationships of the germplasm were
      investigated with 1,727 Diversity Array Technology (DArT) markers. Multiple
      clustering analyses suggest the presence of four subpopulations. Within
      cultivated barley, substructure is largely centered on spike morphology and
      growth habit. Analysis of molecular variance indicated highly significant genetic
      variance among clusters and within clusters, suggesting that the FHB resistant
      sources have broad genetic diversity. The haplotype diversity was characterized
      with DArT markers associated with the four FHB QTLs on chromosome 2H bin8, 10 and
      13 and 6H bin7. In general, the wild barley accessions had distinct haplotypes
      from those of cultivated barley. The haplotype of the resistant source Chevron
      was the most prevalent in all four QTL regions, followed by those of the
      resistant sources Fredrickson and CIho4196. These resistant QTL haplotypes were
      rare in the susceptible cultivars and accessions grown in the upper Midwest USA.
      Some two- and six-rowed accessions were identified with high FHB resistance, but
      contained distinct haplotypes at FHB QTLs from known resistance sources. These
      germplasm warrant further genetic studies and possible incorporation into barley
      breeding programs.

PMID- 23124392
TI  - Modification of response behavior of zinc sensing HydHG two-component system
      using a self-activation loop and genomic integration.
AB  - Characterizing the dynamics of HydHG-a two-component transcriptional regulatory
      network for exogenous zinc in E. coli-is essential in understanding the biology
      of these regulatory and signaling pathways. Here, we used a synthetic biology
      strategy to modify the dynamic characteristics of the HydHG network in two ways.
      First, a self-activation loop for HydHG network was created under the control of
      zraP promoter, after which the threshold Zn(2+) concentration for the self
      activated HydHG network significantly decreased from 200 to 10 MUM. Second, the
      self-activation loop was integrated into the E. coli genome allowing the
      threshold Zn(2+) concentration to be elevated to 500 MUM. As the threshold Zn(2+)
      concentration could be modified in both directions, the introduction of a self
      activation loop and the entire genomic integration strategy may prove useful for
      the creation of a two-component bacterial biosensor with varying sensitivities. 

PMID- 23124393
TI  - Long-range electronic connection in picket-fence like ferrocene-porphyrin
      derivatives.
AB  - The effects of a direct connection between ferrocene and porphyrin units have
      been thoroughly investigated by electrochemical and spectroscopic methods. These
      data not only reveal that substitution of the porphyrin macrocycle by one, two,
      three or four ferrocenyl groups strongly affects the electronic properties of the
      porphyrin and ferrocenyl moieties, they also clearly demonstrate that the
      metallocene centres are "connected" through the porphyrin-based electronic
      network. The dynamic properties of selected ferrocene-porphyrin conjugates have
      been investigated by VT NMR and metadynamic calculations. 1,3-Dithiolanyl
      protecting groups have been introduced on the upper rings of the ferrocene
      fragments to allow a straightforward and easy access to redox active picket-fence
      porphyrins. X-ray diffraction analyses of the zinc(II) 5-[1'-[2-(1,3
      dithiolanyl)]ferrocenyl]-10,15,20-tri(p-tolyl)porphyrin and 5,15-bis[1'-[2-(1,3
      dithiolanyl)]ferrocenyl]-10,20-bis(p-tolyl)porphyrin complexes reveal the
      existence of S-Zn bonds involved in supramolecular arrays. The solid state
      analysis of the trans-5,15-di-(1'-(formyl)ferrocenyl)-10,20-di-(p-tolyl)
      porphyrinatozinc(II) complex, obtained by deprotection of the dithiolane
      substituted analog, is conversely found in the crystal lattice as a monomer
      exhibiting a hexacoordinated zinc metal centre.

PMID- 23124394
TI  - The expression patterns of MHC class I molecules in the developmental human
      visual system.
AB  - It has been considered that healthy neurons in central nervous system (CNS) do
      not express major histocompatibility complex (MHC) class I molecules. However,
      recent studies clearly demonstrated the expression of functional MHC class I in
      the mammalian embryonic, neonatal and adult brain. Until now, it is still unknown
      whether MHC I molecules are expressed in the development of human brain. We
      collected nine human brain tissues from fetuses aged from 21 to 31 gestational
      weeks (GW), one newborn of postnatal 55 days and one adult. The expression of MHC
      class I molecules was detected during the development of visual system in human
      brain by immunohistochemistry and immunofluorescence. MHC class I proteins were
      located at lateral geniculate nucleus (LGN) and the expression was gradually
      increased from 21 GW to 31 GW and reached high levels at 30-31 GW when fine-scale
      refinement phase was mediated by neural electric activity. However, there was no
      expression of MHC class I molecules in the visual cortical cortex during all the
      developmental stages examined. We also concluded that MHC class I molecules were
      mainly expressed in neurons but not in astrocytes at LGN. In the developing
      visual system, the expression of beta2M protein on neurons was not found in our
      study.

PMID- 23124397
TI  - Developing and assessing  medical leadership.

PMID- 23124398
TI  - Changing trends in pituitary surgery.

PMID- 23124396
TI  - Bone density in peripubertal boys with autism spectrum disorders.
AB  - We determined whether bone mineral density (BMD) is lower in boys with autism
      spectrum disorders (ASD) than controls, and also assessed variables that may
      affect BMD in ASD. BMD was measured using dual energy X-ray absorptiometry (DXA)
      in 18 boys with ASD and 19 controls 8-14 years old. Boys with ASD had lower BMD Z
      scores at the spine, hip and femoral neck, and differences at the hip and femoral
      neck persisted after controlling for maturity and BMI. Vitamin D intake from food
      and in serum were lower in ASD subjects, as was exercise activity. We conclude
      that BMD is lower in peripubertal boys with ASD and may be associated with
      impaired vitamin D status and lower exercise activity.

PMID- 23124400
TI  - Combustion-derived air pollution and cardiovascular disease.
AB  - Air pollution is a modifiable risk factor for cardiovascular disease that affects
      the entire population and is thus a major public health concern. It is important
      to understand how air pollution increases cardiovascular risk to develop
      strategies to protect susceptible individuals and reduce the effect of air
      pollution on cardiovascular health.

PMID- 23124401
TI  - New oral anticoagulants:  an alternative to warfarin.
AB  - New agents have been introduced for the prevention of inappropriate thrombosis in
      the vascular tree and the heart. This article reviews, compares and contrasts the
      newer agents which inhibit activated factor X (Xa) or activated factor II
      (thrombin).

PMID- 23124395
TI  - Proteolytic remodeling of the synaptic cell adhesion molecules (CAMs) by
      metzincins in synaptic plasticity.
AB  - Cell adhesion molecules participate in the formation, maturation, function and
      plasticity of synaptic connections. The growing body of evidence indicates that
      in the regulation of the synaptic plasticity, in which these molecules play
      pivotal role, also the proteolytic processes are involved. This review focuses on
      extracellular proteolysis of the cell adhesion molecules by specific subgroup of
      the matrix metalloproteinases, a disintegrin and metalloproteases and a
      disintegrin and metalloproteinase with thrombospondin motifs, jointly referred to
      as metzincins, in driving coordinated synaptic structural and functional
      modifications underlying synaptic plasticity in the adult brain.

PMID- 23124402
TI  - Ventricular arrhythmias complicating hypertrophic cardiomyopathy.
AB  - Hypertrophic cardiomyopathy is the most common genetic cardiovascular disorder
      and the leading cause of sudden cardiac death in the young. This article reviews
      the ventricular arrhythmias associated with hypertrophic cardiomyopathy, the
      difficulties in risk stratification, and current and future therapeutic
      strategies.

PMID- 23124403
TI  - Systemic sclerosis.
AB  - This review updates the clinician on the pathogenesis, differential diagnosis and
      spectrum of disease  in systemic sclerosis. The wide range of current therapeutic
      options and  future targeted molecular therapies are also explored.

PMID- 23124404
TI  - Infections in biological agents used in rheumatic disease.
AB  - Immunosuppression and biological therapies are being used exponentially to treat
      inflammatory arthritis and connective tissue diseases. This article discusses the
      potential infectious complications of these therapies.

PMID- 23124405
TI  - The training needs and career intentions  of staff grade and associate specialist
      doctors.
AB  - This article outlines the results of a study which used an online survey to
      explore the career intentions of staff grade and associate specialist doctors in
      one region and their training needs to inform those managing the continued
      professional development of staff grade and associate specialist doctors.

PMID- 23124406
TI  - Audit of audit: review of a clinical audit programme in a teaching hospital
      intensive care unit.
AB  - OBJECTIVE: A comprehensive review of the clinical audit programme in a teaching
      hospital intensive care unit. DESIGN: A retrospective analysis of the clinical
      audit projects undertaken within the intensive care unit over the preceding 2
      years and compared with published national guidelines for clinical audit.
      SETTING: A 27-bedded teaching hospital intensive care unit in the UK.
      MEASUREMENTS: Each audit project was reviewed independently by two assessors. The
      following questions were assessed. 1. Were the projects true audits? 2. Were they
      prospective of retrospective? 3. Did the projects have input from appropriate
      members of the multidisciplinary team. 4. How many of the audit projects were re
      audits? 5. Of the re-audits how many showed evidence of service improvement? each
      audit project was also scored against the Audit Project Assessment Tool produced
      by the UK Clinical Governance Support Team. RESULTS: Of the twenty five audit
      projects reviewed twenty two were considered to be true audits. All of the
      projects used only retrospective data. Audit projects were contributed from all
      sections of the multidisciplinary critical care team but there were few truly
      multidisciplinary projects. Four of the audit projects were re-audits, of these
      three showed service improvement and one showed deterioration. Of the twenty two
      true audit projects reviewed, eleven were classified as good quality projects
      using the Audit Project Assessment Tool. CONCLUSIONS: Despite the clinical audit
      programme being active and well supported, objective evidence of clinical
      governance benefit was lacking. The overall clinical audit programme has been
      revitalised by a series of improvements since undertaking this review and this
      approach is recommended to other organizations who are interested in improving
      their clinical audit performance.

PMID- 23124407
TI  - Professor Ian Aird: a renowned teacher of surgery.

PMID- 23124408
TI  - Aortic valve insufficiency in antinuclear antibody positive large vessel
      vasculitis.

PMID- 23124409
TI  - Autoimmune haemolytic anaemia in ulcerative colitis.

PMID- 23124410
TI  - Coconut water-induced hyperkalaemia.

PMID- 23124411
TI  - Back to school investments.

PMID- 23124413
TI  - Should endotracheal cuff pressure be routinely measured during elective surgery?

PMID- 23124415
TI  - Fatty acid ethyl esters (FAEEs) as markers for alcohol in meconium: method
      validation and implementation of a screening program for prenatal drug exposure.
AB  - Alcohol consumption during pregnancy is a widespread problem and can cause severe
      fetal damage. As the diagnosis of fetal alcohol syndrome is difficult, the
      implementation of a reliable marker for alcohol consumption during pregnancy into
      meconium drug screening programs would be invaluable. A previously published gas
      chromatography mass spectrometry method for the detection of fatty acid ethyl
      esters (FAEEs) as alcohol markers in meconium was optimized and newly validated
      for a sample size of 50 mg. This method was applied to 122 cases from a drug
      using population. The meconium samples were also tested for common drugs of
      abuse. In 73 % of the cases, one or more drugs were found. Twenty percent of the
      samples tested positive for FAEEs at levels indicating significant alcohol
      exposure. Consequently, alcohol was found to be the third most frequently abused
      substance within the study group. This re-validated method provides an increase
      in testing sensitivity, is reliable and easily applicable as part of a drug
      screening program. It can be used as a non-invasive tool to detect high alcohol
      consumption in the last trimester of pregnancy. The introduction of FAEEs testing
      in meconium screening was found to be of particular use in a drug-using
      population.

PMID- 23124416
TI  - Influence of age, performance status, cancer activity, and IL-6 on anxiety and
      depression in patients with metastatic breast cancer.
AB  - Depression and anxiety are the core disorders causing emotional distress in
      patients (pts) with metastatic breast cancer. The aim of our study was to screen
      metastatic breast cancer outpatients for anxiety and depression, and to
      investigate the influence of age, Karnofsky Performance Status (KPS), cancer
      activity, and inflammation as represented by IL-6 levels on these two mood
      disorders. Pts treated with chemotherapy for metastatic breast cancer (n = 70)
      were assessed using the Hospital Anxiety and Depression Scale (HADS) for symptoms
      (scores 0-21) and caseness (score >=11) of clinical depression and anxiety. Blood
      samples for IL-6 concentrations were collected at 10:00 a.m. A total of 22 (31.4
      %) pts were diagnosed with caseness of clinical depression and 23 (32.9 %) pts
      with clinical anxiety, while 12 pts were diagnosed positive for both mood
      disorders. Depression and anxiety were positively but moderately correlated
      (Spearman's r (2) = 0.24, p < 0.001). IL-6 was significantly correlated with
      symptoms of depression (r (2) = 0.42, p < 0.001) and to a lesser extent to
      symptoms of anxiety (r (2) = 0.16, p = 0.001). In addition, IL-6 was positively
      associated with tumor progression (p < 0.001). Multiple linear regression
      analysis showed that tumor progression (standardized b = 0.226, p = 0.047),
      symptoms of anxiety (b = 0.292, p = 0.016), and IL-6 (b = 0.314, p = 0.007) were
      independently associated with clinical depression, whereas anxiety was linked to
      tumor progression (b = 0.238, p = 0.030), symptoms of depression (b = 0.407, p <
      0.001) and age (b = -0.381, p < 0.001), but not to IL-6 (b = 0.168, p = 0.134).
      Even though a positive correlation between depression and anxiety exists,
      clinical parameters like age, cancer activity, KPS, and IL-6 do influence
      depression and anxiety differently. Unlike clinical depression, anxiety is not
      associated with increased IL-6 levels, however, shows a reciprocal correlation
      with age.

PMID- 23124417
TI  - Association of large noncoding RNA HOTAIR expression and its downstream
      intergenic CpG island methylation with survival in breast cancer.
AB  - Large noncoding RNA HOTAIR, transcribed from the antisense strand of HOXC12,
      interacts with Polycomb Repressive Complex 2 (PRC2) in the regulation of gene
      activities. Recent work suggests that it may have effects on breast cancer
      progression and survival. We evaluated HOTAIR expression and the methylation
      status of its downstream intergenic CpG island in primary breast cancers, and
      examined associations of these factors with clinical and pathologic features and
      patient survival. HOTAIR expression and DNA methylation were analyzed in tissue
      from 348 primary breast cancers with quantitative RT-PCR and methylation-specific
      PCR, respectively. HOTAIR expression and methylation varied widely in the
      tissues. A positive correlation was found between DNA methylation and HOTAIR
      expression. Methylation was associated with unfavorable disease characteristics,
      whereas no significant associations were found between HOTAIR expression and
      clinical or pathologic features. In multivariate, but not in univariate, Cox
      proportional hazard regression models, patients with high HOTAIR expression had
      lower risks of relapse and mortality than those with low HOTAIR expression. These
      findings suggest that the intergenic DNA methylation may have important biologic
      relevance in regulating HOTAIR expression, and that HOTAIR expression may not be
      an independent prognostic marker in breast cancer, but needs further validation
      in independent studies.

PMID- 23124418
TI  - NHS: nobody has solutions?

PMID- 23124419
TI  - A silent epidemic: community nursing and effective pain management.
AB  - Effective pain management presents challenges to health care practitioners,
      particularly in the community setting. This is evident from the complexities
      associated with the phenomenon of pain and the circumstances for those patients
      suffering from pain. An overwhelming amount of literature and research
      surrounding pain exists in an effort to improve our understanding of pain,
      assessment and management strategies. But patients in pain are not managed well
      in the community or acute setting. Health care professionals continue to
      underestimate and under treat pain, failing to meet the patient's individual
      needs. Pain management it is not about cure, nor is it as simple as reporting
      zero on a pain score- it is about knowledge, expertise and understanding. Pain is
      a subjective and very personal experience, wherein health care professionals must
      listen to the patients' story. Myths and fears surrounding pain remains a barrier
      to effective management and care. This article aims to dispel the myths and
      improve clinical practice, particularly in effective pain assessment so patients
      in the community presenting with pain can be managed individually and
      effectively. Nurses need to be proactive in their approach, through effective
      communication and decision making, trusting in our patients' and their pain
      experience. This is key to a successful approach to managing patients' pain
      effectively.

PMID- 23124420
TI  - Case study: the use of telehealth  technology in a community setting.
AB  - Self-care is a great concept and telehealth can give any patient with a long term
      condition the confidence to understand and manage their health better. Patients
      are usually surprised at how small the equipment is and how easy it is to use.
      Giving patients control provides peace of mind and enables nurses to work more
      efficiently and effectively.

PMID- 23124421
TI  - Psoriasis: symptoms, treatments and its impact on quality of life.
AB  - Psoriasis affects between 1% and 3% of the population and there is no cure for
      this chronic skin disease. This article gives an overview of the condition and
      available treatments. It focuses on managing symptoms, the range of medications
      available and the impact this chronic condition can have on a sufferer's quality
      of life. The article looks at medication non adherence remaining the biggest
      obstacle to management of the condition and the debilitating effect psoriasis can
      have on an individual's self-esteem and general well-being. It concludes by
      considering the role of patient support services such as the touch programme.

PMID- 23124422
TI  - Diabetes: support for those at risk  of malnutrition in the community.
AB  - Diet is the cornerstone of treatment in diabetes and dietary advice should be
      tailored to the individual and their circumstances. This article focuses on
      patients with diabetes who are identified as being at risk of malnutrition and
      community nurses are ideally placed to meet patients' continuum of health needs.
      Emphasis should be put on nutritional support, encouraging food fortification
      (some recipes will need adapting), full-fat products and high-energy snacks.
      Diabetes treatment will need to be reviewed regularly to reflect changes in the
      patient's needs. Glycaemic targets need to be agreed with the patient and those
      at risk of hypoglycaemia identified. Strategies should be put in place for
      minimising risk and a clear treatment plan implemented. In cases where the risk
      of malnutrition is resolved, the patient and family may need support returning to
      previous dietary recommendations.

PMID- 23124423
TI  - Reflecting on the black and minority ethnic contribution to palliative care.

PMID- 23124424
TI  - Medication administration in the  domiciliary care setting: whose role?
AB  - Unqualified social care workers are increasingly delegated the responsibility of
      both assisting with and administering medication in the domiciliary care setting.
      This article discusses the considerations required before the delegation of these
      roles by both commissioners and nurses. In particular, variations in training,
      policies and provision are explored with reference to the Care Quality Commission
      guidance and Nursing and Midwifery Council standards. The levels of support and
      their definitions are clarified for use in policy documents, and the
      effectiveness of devices used to support self-care are critiqued within a legal
      framework. The importance of joint working to provide a seamless medication
      management service are highlighted using reflections on examples from practice.

PMID- 23124425
TI  - Developing a district nursing workforce with advanced skills, for care at home.

PMID- 23124427
TI  - The three questions patients need to ask to speed up consultation times.

PMID- 23124428
TI  - Identifying a deprivation of liberty:  a guide for community nurses.
AB  - The ability to identify situations that amount to a deprivation of liberty is
      crucial to a district nurse's role in protecting the vulnerable adults in their
      care. The courts acknowledge that the elements that have to be applied when
      assessing if there is a deprivation of liberty are complex and technical, so it
      is essential that district nurses apply the elements is a methodical manner and
      inform their decision-making by reference to the case law and the Mental Capacity
      Act 2005, Deprivation of Liberty Safeguards Code of Practice. This article
      reviews the European Court of Human Rights and UK domestic case law on
      deprivation of liberty and highlights the elements district nurses must take
      notice of when identifying situations that amount to a deprivation of liberty.

PMID- 23124429
TI  - Getting end of life care right.

PMID- 23124430
TI  - Phenotypic diversity and association mapping for fruit quality traits in
      cultivated tomato and related species.
AB  - Association mapping has been proposed as an efficient approach to assist in the
      identification of the molecular basis of agronomical traits in plants. For this
      purpose, we analyzed the phenotypic and genetic diversity of a large collection
      of tomato accessions including 44 heirloom and vintage cultivars (Solanum
      lycopersicum), 127 S. lycopersicum var. cerasiforme (cherry tomato) and 17
      Solanum pimpinellifolium accessions. The accessions were genotyped using a
      SNPlexTM assay of 192 SNPs, among which 121 were informative for subsequent
      analysis. Linkage disequilibrium (LD) of pairwise loci and population structure
      were analyzed, and the association analysis between SNP genotypes and ten fruit
      quality traits was performed using a mixed linear model. High level of LD was
      found in the collection at the whole genome level. It was lower when considering
      only the 127 S. lycopersicum var. cerasiforme accessions. Genetic structure
      analysis showed that the population was structured into two main groups,
      corresponding to cultivated and wild types and many intermediates. The number of
      associations detected per trait varied, according to the way the structure was
      taken into account, with 0-41 associations detected per trait in the whole
      collection and a maximum of four associations in the S. lycopersicum var.
      cerasiforme accessions. A total of 40 associations (30 %) were co-localized with
      previously identified quantitative trait loci. This study thus showed the
      potential and limits of using association mapping in tomato populations.

PMID- 23124431
TI  - QTL mapping in three tropical maize populations reveals a set of constitutive and
      adaptive genomic regions for drought tolerance.
AB  - Despite numerous published reports of quantitative trait loci (QTL) for drought
      related traits, practical applications of such QTL in maize improvement are
      scarce. Identifying QTL of sizeable effects that express more or less uniformly
      in diverse genetic backgrounds across contrasting water regimes could
      significantly complement conventional breeding efforts to improve drought
      tolerance. We evaluated three tropical bi-parental populations under water-stress
      (WS) and well-watered (WW) regimes in Mexico, Kenya and Zimbabwe to identify
      genomic regions responsible for grain yield (GY) and anthesis-silking interval
      (ASI) across multiple environments and diverse genetic backgrounds. Across the
      three populations, on average, drought stress reduced GY by more than 50 % and
      increased ASI by 3.2 days. We identified a total of 83 and 62 QTL through
      individual environment analyses for GY and ASI, respectively. In each population,
      most QTL consistently showed up in each water regime. Across the three
      populations, the phenotypic variance explained by various individual QTL ranged
      from 2.6 to 17.8 % for GY and 1.7 to 17.8 % for ASI under WS environments and
      from 5 to 19.5 % for GY under WW environments. Meta-QTL (mQTL) analysis across
      the three populations and multiple environments identified seven genomic regions
      for GY and one for ASI, of which six mQTL on chr.1, 4, 5 and 10 for GY were
      constitutively expressed across WS and WW environments. One mQTL on chr.7 for GY
      and one on chr.3 for ASI were found to be 'adaptive' to WS conditions. High
      throughput assays were developed for SNPs that delimit the physical intervals of
      these mQTL. At most of the QTL, almost equal number of favorable alleles was
      donated by either of the parents within each cross, thereby demonstrating the
      potential of drought tolerant * drought tolerant crosses to identify QTL under
      contrasting water regimes.

PMID- 23124432
TI  - An eceriferum locus, cer-zv, is associated with a defect in cutin responsible for
      water retention in barley (Hordeum vulgare) leaves.
AB  - Drought limits plant growth and threatens crop productivity. A barley (Hordeum
      vulgare) ethylene imine-induced monogenic recessive mutant cer-zv, which is
      sensitive to drought, was characterized and genetically mapped in the present
      study. Detached leaves of cer-zv lost 34.2 % of their initial weight after 1 h of
      dehydration. The transpiration was much higher in cer-zv leaves than in wild-type
      leaves under both light and dark conditions. The stomata of cer-zv leaves
      functioned normally, but the cuticle of cer-zv leaves showed increased
      permeability to ethanol and toluidine blue dye. There was a 50-90 % reduction in
      four major cutin monomers, but no reduction in wax loads was found in the cer-zv
      mutant as compared with the wild type. Two F(2) mapping populations were
      established by the crosses of 23-19 * cer-zv and cer-zv * OUH602. More
      polymorphisms were found in EST sequences between cer-zv and OUH602 than between
      cer-zv and 23-19. cer-zv was located in a pericentromeric region on chromosome 4H
      in a 10.8 cM interval in the 23-19 * cer-zv map based on 186 gametes tested and a
      1.7 cM interval in the cer-zv * OUH602 map based on 176 gametes tested. It co
      segregated with EST marker AK251484 in both maps. The results indicated that the
      cer-zv mutant is defective in cutin, which might be responsible for the increased
      transpiration rate and drought sensitivity, and that the F(2) of cer-zv * OUH602
      might better facilitate high resolution mapping of cer-zv.

PMID- 23124433
TI  - Identification of functional tissue-resident cardiac stem/progenitor cells in
      adult mouse.
AB  - In most somatic tissues, ASCs (adult stem cells) are crucial for the maintenance
      of tissue homoeostasis under normal physiological state and recovery from injury.
      LRC (label retaining cell) assay is a well-known method of identifying possible
      somatic stem/progenitor cells and their location both in situ and in vivo. BrdU
      (bromodeoxyuridine) was used here to tag the possible CSCs (cardiac stem
      cells)/CPCs (cardiac progenitor cells) in newborn pups, followed by a trace
      period of up to 24 months. In addition, we have used our newly developed 'KAL'
      method to rapidly Kill proliferating cells in adult heart tissues, then, Activate
      and Label the surviving CSCs/CPCs. LRCs that definitively exist in the heart
      tissues of adult mice, and some LRCs express the stem cell marker, Sca-1 or c
      Kit, and are located primarily in the myocardium and vascular endothelial
      regions. Moreover, the number of LRCs remains nearly constant during the lifespan
      of the mouse. After injury induced by 5-fluorouracil, the proliferating cells
      were almost completely cleared on day 3, and the activated CSCs/CPCs retained
      their BrdU label after regeneration was complete. A small percentage of the
      CSCs/CPCs express Sca-1 or c-Kit. Furthermore, the LRC method together with KAL
      may be used to identify and locate possible CSCs/CPCs, which has potential
      clinical application.

PMID- 23124434
TI  - Peroxide induced tin oxide coating of graphene oxide at room temperature and its
      application for lithium ion batteries.
AB  - We describe a new, simple and low-temperature method for ultra-thin coating of
      graphene oxide (GO) by peroxostannate, tin oxide or a mixture of tin and tin
      oxide crystallites by different treatments. The technique is environmentally
      friendly and does not require complicated infrastructure, an autoclave or a
      microwave. The supported peroxostannate phase is partially converted after drying
      to crystalline tin oxide with average, 2.5 nm cassiterite crystals. Mild heat
      treatment yielded full coverage of the reduced graphene oxide by crystalline tin
      oxide. Extensive heat treatment in vacuum at >500  degrees C yielded a mixture of
      elemental tin and cassiterite tin oxide nanoparticles supported on reduced
      graphene oxide (rGO). The usefulness of the new approach was demonstrated by the
      preparation of two types of lithium ion anodes: tin oxide-rGO and a mixture of
      tin oxide and tin coated rGO composites (SnO(2)-Sn-rGO). The electrodes exhibited
      stable charge/discharge cyclability and high charging capacity due to the
      intimate contact between the conductive graphene and the very small tin oxide
      crystallites. The charging/discharging capacity of the anodes exceeded the
      theoretical capacity predicted based on tin lithiation. The tin oxide coated rGO
      exhibited higher charging capacity but somewhat lower stability upon extended
      charge/discharge cycling compared to SnO(2)-Sn-rGO.

PMID- 23124435
TI  - Sequence variants in eukaryotic translation initiation factor 4-gamma (eIF4G1)
      are associated with Lewy body dementia.
AB  - We recently reported a missense mutation and four variants in eukaryotic
      translation initiation factor 4-gamma (EIF4G1) associated with parkinsonism,
      dementia or both. In those with a positive family history, the mode of
      inheritance was autosomal dominant. Detailed neuropathologic descriptions of
      individuals with EIF4G1 genetic variants have not been reported. Herein, we
      report neuropathologic findings of three individuals from two American families
      with EIF4G1 variants. The patients had initial clinical presentations of dementia
      or parkinsonism and all had dementia at the time of autopsy. One family carried
      an EIF4G1 double variant, c.2056G>T (p.G686C) and c.3589C>T (p.R1197 W), and one
      family carried variant c.1505C>T (p.A502V). All three patients also carried at
      least one epsilon4 allele of apolipoprotein E. One individual presented with
      cognitive impairment without significant parkinsonism; one presented with memory
      problems followed by bradykinesia; and the third presented with cardinal signs of
      Parkinson's disease, followed more than a year later by cognitive dysfunction.
      Pathological examination showed diffuse cortical Lewy bodies and Lewy neurites in
      all patients. A small subset of Lewy bodies and Lewy neurites were immunopositive
      for eIF4G1. All patients had moderate to frequent non-neuritic, cortical amyloid
      plaques, mostly medial temporal neurofibrillary pathology (Braak neurofibrillary
      tangle stages of II to IV), and minimal or no TDP-43 pathology. The results
      suggest that in some patients variants in EIF4G1 can be associated with pathology
      that has a high likelihood of association with clinical features of dementia with
      Lewy bodies.

PMID- 23124436
TI  - Rapeseed-straw enzymatic digestibility enhancement by sodium hydroxide treatment
      under ultrasound irradiation.
AB  - In this study, we carried out sodium hydroxide and sonication pretreatments of
      rapeseed straw (Brassica napus) to obtain monosugar suitable for production of
      biofuels. To optimize the pretreatment conditions, we applied a statistical
      response-surface methodology. The optimal pretreatment conditions using sodium
      hydroxide under sonication irradiation were determined to be 75.0  degrees C, 7.0
      % sodium hydroxide, and 6.8 h. For these conditions, we predicted 97.3 %
      enzymatic digestibility. In repeated experiments to validate the predicted value,
      98.9 +/- 0.3 % enzymatic digestibility was obtained, which was well within the
      range of the predicted model. Moreover, sonication irradiation was found to have
      a good effect on pretreatment in the lower temperature range and at all
      concentrations of sodium hydroxide. According to scanning electron microscopy
      images, the surface area and pore size of the pretreated rapeseed straw were
      modified by the sodium hydroxide pretreatment under sonication irradiation.

PMID- 23124437
TI  - Validation of tumor markers in central nervous system germ cell tumors by real
      time reverse transcriptase polymerase chain reaction using formalin-fixed
      paraffin-embedded tissues.
AB  - The therapeutic protocols for treatment of germinomas and non-germinomatous germ
      cell tumors (NGGCTs) are completely different, so it is important to distinguish
      pure germinomas from NGGCTs. As it can be difficult to diagnose by morphology
      alone, immunohisto-chemistry (IHC) has been widely used as an ancillary test to
      improve diagnostic accuracy. However, IHC has limitations due to the
      misinterpretation of results or the aberrant loss of immunoreactivity. However,
      real-time RT-PCR has certain advantages over IHC, including its quantitative
      nature. The aim of our study was to evaluate the usefulness of real-time RT-PCR
      on formalin-fixed paraffin-embedded (FFPE) tissue blocks for the diagnosis of
      germ cell tumors of the central nervous system. We selected eight markers of germ
      cell tumors using a literature search, and validated them using real-time RT-PCR.
      Among them, POU5F1, NANOG and TGFB2 were statistically significant (P=0.05) in
      multiple comparisons (MANOVA) of three groups (pure germinomas, mature teratomas
      and malignant germ cell tumors). Two-group (pure germinomas and NGGCTs)
      discriminant analysis achieved a 70.0% success rate in cross-validation. We
      concluded that real-time RT-PCR using FFPE tissue has adequate validating power
      comparable to IHC in the diagnosis of central nervous system germ cell tumors;
      therefore, when IHC is not available, not conclusive or not informative, RT-PCR
      is a potential alternative to a repeat biopsy. 

PMID- 23124438
TI  - Comment on Marciano et. al.: Effects of type 2 diabetes mellitus on coronary
      microvascular function and myocardial perfusion in patients without obstructive
      coronary artery disease.

PMID- 23124439
TI  - Effects of type 2 diabetes mellitus on coronary microvascular function and
      myocardial perfusion in patients without obstructive coronary artery disease:
      reply to Presotto.

PMID- 23124440
TI  - Combined administration of rituximab and on 013105 induces apoptosis in mantle
      cell lymphoma cells and reduces tumor burden in a mouse model of mantle cell
      lymphoma.
AB  - PURPOSE: Mantle cell lymphoma (MCL) is an incurable B-cell lymphoma, and new
      therapeutic strategies are urgently needed. EXPERIMENTAL DESIGN: The effects of
      ON 013105, a novel benzylstyryl sulfone kinase inhibitor, alone or with
      doxorubicin or rituximab, were examined in Granta 519 and Z138C cells. For in
      vivo studies, CB17/SCID mice were implanted subcutaneously with Z138C cells and
      treated with various combinations of ON 013105, doxorubicin, and rituximab. Tumor
      burden and body weight were monitored for 28 days. RESULTS: ON 013105 induced
      mitochondria-mediated apoptosis in MCL cells. Death was preceded by translocation
      of tBid to the mitochondria and cytochrome c release. In addition, ON 013105
      treated cells exhibited reduced levels of cyclin D1, c-Myc, Mcl-1, and Bcl-xL.
      Using nuclear magnetic resonance (NMR) spectroscopy, we showed specific binding
      of ON 013105 to eIF4E, a critical factor for the initiation of protein
      translation. We proffer that this drug-protein interaction preferentially
      prevents the translation of the aforementioned proteins and may be the mechanism
      by which ON 013105 induces apoptosis in MCL cells. Efficacy studies in a mouse
      xenograft model showed that ON 013105 inhibited MCL tumor growth and that
      combining ON 013105 with rituximab reduced tumor burden further with negligible
      unwanted effects. CONCLUSIONS: Our findings suggest that ON 013105, alone or in
      combination with rituximab, may be a potent therapeutic agent to treat MCLs.

PMID- 23124441
TI  - Domestic dogs conceal auditory but not visual information from others.
AB  - A number of studies have shown that dogs are sensitive to a human's perspective,
      but it remains unclear whether they use an egocentric strategy to assess what
      humans perceive. We investigated whether dogs know what a human can see and hear,
      even when the dogs themselves are unable to see the human. Dogs faced a task in
      which forbidden food was placed in a tunnel that they could retrieve by using
      their paw. Whereas the dogs could not see the experimenter during their food
      retrieval attempts, the experimenter could potentially see the dog's paw. In the
      first experiment, dogs could choose between an opaque and a transparent side of
      the tunnel, and in the second experiment, they could choose between a silent and
      a noisy approach to the tunnel. The results showed that dogs preferred a silent
      approach to forbidden food but they did not hide their approach when they could
      not see a human present. We conclude that dogs probably rely on what they
      themselves can perceive when they assess what the human can see and hear.

PMID- 23124442
TI  - Animal-assisted intervention for autism spectrum disorder: a systematic
      literature review.
AB  - The inclusion of animals in therapeutic activities, known as animal-assisted
      intervention (AAI), has been suggested as a treatment practice for autism
      spectrum disorder (ASD). This paper presents a systematic review of the empirical
      research on AAI for ASD. Fourteen studies published in peer-reviewed journals
      qualified for inclusion. The presentation of AAI was highly variable across the
      studies. Reported outcomes included improvements for multiple areas of
      functioning known to be impaired in ASD, namely increased social interaction and
      communication as well as decreased problem behaviors, autistic severity, and
      stress. Yet despite unanimously positive outcomes, most studies were limited by
      many methodological weaknesses. This review demonstrates that there is
      preliminary "proof of concept" of AAI for ASD and highlights the need for
      further, more rigorous research.

PMID- 23124443
TI  - Why be against Darwin? Creationism, racism, and the roots of anthropology.
AB  - In this work, I review recent works in science studies and the history of science
      of relevance to biological anthropology. I will look at two rhetorical practices
      in human evolution--overstating our relationship with the apes and privileging
      ancestry over emergence--and their effects upon how human evolution and human
      diversity have been understood scientifically. I examine specifically the
      intellectual conflicts between Rudolf Virchow and Ernst Haeckel in the 19th
      century and G. G. Simpson and Morris Goodman a century later. This will expose
      some previously concealed elements of the tangled histories of anthropology,
      genetics, and evolution-particularly in relation to the general roles of race and
      heredity in conceptualizing human origins. I argue that scientific racism and
      unscientific creationism are both threats to the scholarly enterprise, but that
      scientific racism is worse.

PMID- 23124444
TI  - Mononuclear and dinuclear Re(I) complexes incorporating 1-(2-pyridylazo)-2
      naphthol: synthesis, structure, spectral, DFT and TDDFT studies.
AB  - The Re(I) complexes [Re(HPAN)(CO)(3)Cl], 1, and [Re(2)(PAN)(2)(CO)(6)].C(6)H(12),
      2.C(6)H(12), have been prepared by reacting [Re(CO)(5)Cl] with HPAN. Here (PAN)(
      ) is the deprotonated form of 1-(2-pyridylazo)-2-naphthol. A subsequent reaction
      of [Re(HPAN)(CO)(3)(CF(3)SO(3))] with a chelating diphosphine ligand generates
      [Re(PAN)(CO)(P-P)].CH(2)Cl(2), 3.CH(2)Cl(2). The structures of the complexes are
      determined by X-ray crystallography. The molecular structures observed in the
      solid state are retained in the solution ((1)H, (13)C and (31)P NMR and mass
      spectra). The photophysical and electrochemical properties are also investigated.
      The gas-phase geometry optimization and the electronic structures of
      [Re(HPAN)(CO)(3)Cl], [Re(2)(PAN)(2)(CO)(6)] and [Re(PAN)(CO)(P-P)] have been
      investigated with the framework of density functional theory. The absorption
      spectra of the complexes are calculated by time dependent density functional
      theory (TDDFT) using a conductor-like polarizable continuum model (CPCM). DFT
      calculation shows good agreement with the experimental ground state IR and NMR
      values. Excited state TDDFT calculations provide a better insight into the
      experimental luminescence spectra of all the complexes in solution.

PMID- 23124446
TI  - Cadmium(II) chloride, bromide and iodide complexes with 4,4'-bipyridazine: when
      are diazine and halide bridges (in)compatible?
AB  - In poly[di-MU-chlorido-MU-(4,4'-bipyridazine)-kappa(2)N(1):N(1')-cadmium(II)],
      [CdCl(2)(C(8)H(6)N(4))](n), (I), and its isomorphous bromide analogue,
      [CdBr(2)(C(8)H(6)N(4))](n), (II), the halide atom lies on a mirror plane and the
      Cd(II) ion resides at the intersection of two perpendicular mirror planes with
      m2m site symmetry. The pyridazine rings of the ligand lie in a mirror plane and
      are related to each other by a second mirror plane perpendicular to the first.
      The compounds adopt the characteristic structure of the [M(II)X(2)(bipy)] type
      (bipy is bipyridine) based on crosslinking of [Cd(MU-X)(2)](n) chains [Cd-Cl =
      2.5955 (9) and 2.6688 (9) A; Cd-Br = 2.7089 (4) and 2.8041 (3) A] by bitopic rod
      like organic ligands [Cd-N = 2.368 (3)-2.380 (3) A]. This feature is discussed in
      terms of supramolecular stabilization, implying that the periodicity of the
      inorganic chain [Cd...Cd = 3.7802 (4) A in (I) and 3.9432 (3) A in (II)] is
      favourable for extensive parallel pi-pi stacking of monodentate pyridazine rings,
      with centroid-centroid distances of 3.7751 (4) A in (I) and 3.9359 (4) A in (II).
      This is not the case for the longer iodide bridges, which cannot stabilize such a
      pattern. In poly[tetra-MU-iodido-MU(4)-(4,4'-bipyridazine)
      kappa(4)N(1):N(2):N(1'):N(2')-dicadmium(II)], [Cd(2)I(4)(C(8)H(6)N(4))](n),
      (III), the ligands are situated across a centre of inversion; they are
      tetradentate [Cd-N = 2.488 (2) and 2.516 (2) A] and link successive [Cd(MU
      I)(2)](n) chains [Cd-I = 2.8816 (3)-3.0069 (4) A] into corrugated layers.

PMID- 23124447
TI  - trans-Chloridobis[(Z)-1-imino-1-methoxyethane-kappaN](triphenylphosphane
      kappaP)platinum(II) chloride monohydrate.
AB  - The title compound, [PtCl(C(3)H(7)NO)(2)(C(18)H(15)P)]Cl.H(2)O or trans-[PtCl{Z
      HN=C(Me)OMe}(2)(PPh(3))]Cl.H(2)O, crystallizes from an acetone solution of
      isomeric trans-[PtCl{E-HN=C(Me)OMe}(2)(PPh(3))]Cl. The two HN=C(Me)OMe ligands
      show typical pi-bond delocalization over the N-C-O group [Cini, Caputo, Intini &
      Natile (1995). Inorg. Chem. 34, 1130-1137] and have the unprecedented Z-anti
      configuration. The relative orientation of the imino ether ligands is head-to
      tail.

PMID- 23124445
TI  - Zone-specific gene expression patterns in articular cartilage.
AB  - OBJECTIVE: To identify novel genes and pathways specific to the superficial zone
      (SZ), middle zone (MZ), and deep zone (DZ) of normal articular cartilage.
      METHODS: Articular cartilage was obtained from the knees of 4 normal human
      donors. The cartilage zones were dissected on a microtome. RNA was analyzed on
      human genome arrays. The zone-specific DNA array data obtained from human tissue
      were compared to array data obtained from bovine cartilage. Genes differentially
      expressed between zones were evaluated using direct annotation for structural or
      functional features, and by enrichment analysis for integrated pathways or
      functions. RESULTS: The greatest differences in genome-wide RNA expression data
      were between the SZ and DZ in both human and bovine cartilage. The MZ, being a
      transitional zone between the SZ and DZ, thereby shared some of the same pathways
      as well as structural/functional features of the adjacent zones. Cellular
      functions and biologic processes that were enriched in the SZ relative to the DZ
      included, most prominently, extracellular matrix-receptor interactions, cell
      adhesion molecule functions, regulation of actin cytoskeleton, ribosome-related
      functions, and signaling aspects such as the IFN, IL4, Cdc42/Rac, and JAK/STAT
      signaling pathways. Two pathways were enriched in the DZ relative to the SZ,
      including PPARG and EGFR/SMRTE. CONCLUSION: These differences in cartilage zonal
      gene expression identify new markers and pathways that govern the unique
      differentiation status of chondrocyte subpopulations.

PMID- 23124448
TI  - catena-Poly[[[diaqua[3-(pyridin-4-yl)benzoato-kappa2O,O']terbium(III)]-bis[MU-3
      (pyridin-4-yl)benzoato-kappa2O:O']] monohydrate].
AB  - In the title compound, {[Tb(C(12)H(8)NO(2))(3)(H(2)O)(2)].H(2)O}(n), the Tb(III)
      cation is in an eight-coordinate environment, ligated by six carboxylate O atoms
      from five 3-(pyridin-4-yl)benzoate (L) ligands and by two O atoms from water
      molecules. The cations are bridged by the carboxylate O atoms of the L ligands to
      form a two-stranded polymeric chain which is assembled into a three-dimensional
      supramolecular network through regular interchain O-H...N hydrogen bonding. On
      excitation at 320 nm, the title compound displays a series of emissions, which
      were assigned to the characteristic electronic transitions of Tb(III).

PMID- 23124449
TI  - A new two-dimensional cadmium metal-organic framework: poly[bis(4,7-diphenyl-1,10
      phenanthroline)(MU3-5-nitroisophthalato)cadmium(II)].
AB  - In the title cadmium metal-organic framework complex,
      [Cd(C(8)H(3)NO(6))(C(24)H(16)N(2))](n) or [Cd(NIPH)(dpphen)] (NIPH is
      nitroisophthalate and dpphen is 4,7-diphenyl-1,10-phenanthroline), the unique
      Cd(II) cation in a general position is coordinated by four carboxy O atoms from
      three symmetry-related NIPH anions and two N atoms from a dpphen ligand. The
      Cd(II) cations are bridged by pairs of NIPH anions to generate a dinuclear
      molecular building block, [Cd(2)N(4)(CO(2)R)(4)], with a Cd...Cd separation of
      4.0936 (10) A. Each such building block is connected to four adjacent dinuclear
      building blocks by NIPH anions, resulting in a two-dimensional layer framework in
      the bc plane. The dpphen ligands occupy the space between these layers and are
      linked by pi-pi interactions, with a separation of 3.4541 (6) A between the
      central aromatic rings of inversion-related dpphen ligands. The thermogravimetric
      and photoluminescent properties of the complex have also been investigated.

PMID- 23124450
TI  - A fivefold interpenetrating diamond-like three-dimensional metal-organic
      framework: poly[(MU2-benzene-1,4-diacetato)[MU2-1,6-bis(1,2,4-triazol-1
      yl)hexane]zinc(II)].
AB  - In the mixed-ligand metal-organic title polymeric compound,
      [Zn(C(10)H(8)O(4))(C(10)H(16)N(6))](n) or [Zn(PBEA)(BTH)](n) [H(2)PBEA is benzene
      1,4-diacetic acid and BTH is 1,6-bis(1,2,4-triazol-1-yl)hexane], the asymmetric
      unit contains a Zn(II) atom, one half of a BTH ligand and one half of a doubly
      deprotonated H(2)PBEA ligand. Each Zn(II) centre lies on a crystallographic
      twofold rotation axis and is four-coordinated by two O atoms from two distinct
      PBEA(2-) ligands and two N atoms from two different BTH ligands in a {ZnO(2)N(2)}
      coordination environment. The three-dimensional topology of the title compound
      corresponds to that of a fivefold interpenetrating diamond-like metal-organic
      framework.

PMID- 23124451
TI  - Poly[di-MU-aqua-[MU6-N-(4-bromophenylsulfonyl)dithiocarbimato]dipotassium] and
      poly[di-MU-aqua-[MU4-N-(4-iodophenylsulfonyl)dithiocarbimato]dipotassium].
AB  - The rigid organic linkers N-(4-bromophenylsulfonyl)dithiocarbimate(2-) and N-(4
      iodophenylsulfonyl)dithiocarbimate(2-) crystallize with two potassium cations and
      two water molecules in their asymmetric units, forming the title coordination
      polymers, [K(2)(C(7)H(4)BrNO(2)S(3))(H(2)O)(2)](n) and
      [K(2)(C(7)H(4)INO(2)S(3))(H(2)O)(2)](n). The anions and the water molecules link
      the potassium cations into broad two-dimensional networks, which are further
      linked by K...halide interactions.

PMID- 23124452
TI  - Dichlorido{2-[(3,5-diphenyl-1H-pyrazol-1-yl-kappaN2)methyl]pyridine
      kappaN}palladium(II).
AB  - The title compound, [PdCl(2)(C(21)H(17)N(3))], is a member of a sequence of Pd,
      Pt and Co dichloride complexes bearing polysubstituted (pyrazol-1
      ylmethyl)pyridine ligands. It is shown that there is a correlation between the
      steric bulkiness of the bidentate (pyrazol-1-ylmethyl)pyridine ligands and the Pd
      N(pyrazole) distances, i.e. the larger the ligand, the longer the bond. In
      contrast, no trend is observed between the steric properties of the ligand and
      the Pd-N(pyridine) bond lengths.

PMID- 23124453
TI  - [N,N'-Bis(2,6-diisopropylphenyl)acenaphthene-1,2-diimine
      1kappa2N,N']heptacarbonyl-1kappaC,2kappa3C,3kappa3C-di-MU3-tellurido
      triiiron(II)(2 Fe-Fe).
AB  - The sterically hindered title complex, [Fe(3)Te(2)(C(36)H(40)N(2))(CO)(7)], was
      obtained by substitution of two carbonyl groups in the [Fe(3)(MU(3)
      Te)(2)(CO)(9)] cluster by the bulky redox-active N,N'-bis(2,6
      diisopropylphenyl)acenaphthene-1,2-diimine (dpp-BIAN) ligand. The asymmetric unit
      contains two molecules of the same geometry. The C=N bond lengths in dpp-BIAN
      indicate a rather low level of electron transfer from the cluster core to the dpp
      BIAN ligand.

PMID- 23124454
TI  - X-(Diiodoarsanyl)benzoic acid (X = 3 and 4).
AB  - The title compounds, 4-(diiodoarsanyl)benzoic acid, (I), and 3
      (diiodoarsanyl)benzoic acid, (II), both [As(C(7)H(5)O(2))I(2)], which possess a 
      COOH coordinating group, form molecular crystal structures composed of hydrogen
      bonded dimers, the packing differences of which are caused by the relative
      position of the diiodoarsanyl groups. The para isomer, with Z' = 1, crystallizes
      in a layered structure with shortened contacts of the As atoms to only the arene
      rings of adjacent molecules. In contrast, the meta isomer, with Z' = 3, forms
      separate rectangular blocks of three ribbons, each composed of dimeric molecular
      units positioned almost directly above each other and with the As atoms
      possessing only two As...I contacts to the I atoms of neighbouring molecules.

PMID- 23124455
TI  - X-ray and DFT studies of a mono- and binuclear copper(II) ionic compound
      containing a Schiff base.
AB  - In the structure of trans-bis(ethanol-kappaO)tetrakis(1H-imidazole
      kappaN(3))copper(II) bis[MU-N-(2-oxidobenzylidene)-D,L-glutamato]
      kappa(4)O(1),N,O(2'):O(2');kappa(4)O(2'):O(1),N,O(2')-bis[(1H-imidazole
      kappaN(3))cuprate(II)],
      [Cu(C(3)H(4)N(2))(4)(C(2)H(6)O)(2)][Cu(2)(C(15)H(14)N(3)O(5))(2)], both ions are
      located on centres of inversion. The cation is mononuclear, showing a distorted
      octahedral coordination, while the anion is a binuclear centrosymmetric dimer
      with a square-pyramidal copper(II) coordination. An extensive three-dimensional
      hydrogen-bonding network is formed between the ions. According to B3LYP/6-31G*
      calculations, the two equivalent components of the anion are in doublet states
      (spin density located mostly on Cu(II) ions) and are coupled as a triplet, with
      only marginal preference over an open-shell singlet.

PMID- 23124456
TI  - The inner-salt zwitterion, the dihydrochloride dihydrate and the dimethyl
      sulfoxide disolvate of 3,6-bis(pyridin-2-yl)pyrazine-2,5-dicarboxylic acid.
AB  - In the inner-salt zwitterion of 3,6-bis(pyridin-2-yl)pyrazine-2,5-dicarboxylic
      acid, (I), namely 5-carboxy-3-(pyridin-1-ium-2-yl)-6-(pyridin-2-yl)pyrazine-2
      carboxylate, [C(16)H(10)N(4)O(4), (Ia)], the pyrazine ring has a twist-boat
      conformation. The opposing pyridine and pyridinium rings are almost perpendicular
      to one another, with a dihedral angle of 80.24 (18) degrees , and are inclined to
      the pyrazine mean plane by 36.83 (17) and 43.74 (17) degrees , respectively. The
      carboxy and carboxylate groups are inclined to the mean plane of the pyrazine
      ring by 43.60 (17) and 45.46 (17) degrees , respectively. In the crystal
      structure, the molecules are linked via N-H...O and O-H...O hydrogen bonds,
      leading to the formation of double-stranded chains propagating in the [010]
      direction. On treating (Ia) with aqueous 1 M HCl, the diprotonated dihydrate form
      2,2'-(3,6-dicarboxypyrazine-2,5-diyl)bis(pyridin-1-ium) dichloride dihydrate
      [C(16)H(12)N(4)O(4)(2+).2Cl(-).2H(2)O, (Ib)] was obtained. The cation lies about
      an inversion centre. The pyridinium rings and carboxy groups are inclined to the
      planar pyrazine ring by 55.53 (9) and 19.8 (2) degrees , respectively. In the
      crystal structure, the molecules are involved in N-H...Cl, O-H...O(water) and
      O(water)-H...Cl hydrogen bonds, leading to the formation of chains propagating in
      the [010] direction. When (Ia) was recrystallized from dimethyl sulfoxide (DMSO),
      the DMSO disolvate 3,6-bis(pyridin-2-yl)pyrazine-2,5-dicarboxylic acid dimethyl
      sulfoxide disolvate [C(16)H(10)N(4)O(4).2C(2)H(6)OS, (Ic)] of (I) was obtained.
      Here, the molecule of (I) lies about an inversion centre and the pyridine rings
      are inclined to the planar pyrazine ring by only 23.59 (12) degrees . However,
      the carboxy groups are inclined to the pyrazine ring by 69.0 (3) degrees . In the
      crystal structure, the carboxy groups are linked to the DMSO molecules by O-H...O
      hydrogen bonds. In all three crystal structures, the presence of nonclassical
      hydrogen bonds gives rise to the formation of three-dimensional supramolecular
      architectures.

PMID- 23124457
TI  - Oxycodone N-oxide.
AB  - The title compound, (5R,9R,13S,14S,17R)-14-hydroxy-3-methoxy-17-methyl-4,5
      epoxymorphinan-6-one N-oxide, C(18)H(21)NO(5), has been prepared in a
      diastereomerically pure form by the reaction of oxycodone with 3-chloroperbenzoic
      acid and subsequent crystallization of the product from chloroform. The crystal
      packing shows that the molecule exhibits intramolecular O-H...O [D...A = 2.482
      (2) A] hydrogen bonding. In addition, there are weak intermolecular C-H...O
      interactions which, along with van der Waals forces, stabilize the structure. The
      new chiral center at the 17-position is demonstrated to be R.

PMID- 23124458
TI  - Methyl (3aRS,3cRS,6cSR,7RS,8RS,8aSR)-2,5-bis(4-chlorophenyl)-7,9-bis(1,3-diphenyl
      1H-pyrazol-4-yl)-1,3,4,6-tetraoxododecahydro-1H-dipyrrolo[3,4-a:3',4'
      f]pyrrolizine-3b-carboxylate dimethylformamide disolvate: a three-dimensional
      hydrogen-bonded framework.
AB  - The racemic title dipyrrolopyrrolizine compound crystallizes from
      dimethylformamide as a disolvate, C(55)H(39)Cl(2)N(7)O(6).2C(3)H(7)NO. None of
      the four fused heterocyclic rings is planar; one adopts an envelope conformation,
      two others adopt half-chair conformations and the fourth adopts a conformation
      intermediate between an envelope and a half-chair. The arrangement of the ring
      fusions is such as to preclude the possibility of internal mirror symmetry. The
      three independent molecular components are weakly linked by C-H...O hydrogen
      bonds, and the dipyrrolopyrrolizine molecules are linked by a combination of four
      C-H...O and one C-H...pi(arene) hydrogen bond to form a three-dimensional
      framework, from which the dimethylformamide solvent molecules are pendent.
      However, aromatic pi-pi stacking interactions are absent in the structure.

PMID- 23124459
TI  - Perindoprilat monohydrate.
AB  - The title compound [systematic name: (1S)-2-((S)-{1-[(2S,3aS,7aS)-2
      carboxyoctahydro-1H-indol-1-yl]-1-oxopropan-2-yl}azaniumyl)pentanoate
      monohydrate], C(17)H(28)N(2)O(5).H(2)O, (I).H(2)O, the active metabolite of the
      antihypertensive and cardiovascular drug perindopril, was obtained during
      polymorphism screening of perindoprilat. It crystallizes in the chiral
      orthorhombic space group P2(1)2(1)2(1), the same as the previously reported
      ethanol disolvate [Pascard, Guilhem, Vincent, Remond, Portevin & Laubie (1991).
      J. Med. Chem. 34, 663-669] and dimethyl sulfoxide hemisolvate [Bojarska,
      Maniukiewicz, Sieron, Fruzinski, Kopczacki, Walczynski & Remko (2012). Acta
      Cryst. C68, o341-o343]. The asymmetric unit of (I).H(2)O contains one independent
      perindoprilat zwitterion and one water molecule. These interact via strong
      hydrogen bonds to give a cyclic R(2)(2)(7) synthon, which provides a rigid
      molecular conformation. The geometric parameters of all three forms are similar.
      The conformations of the perhydroindole group are almost identical, but the n
      alkyl chain has conformational freedom. A three-dimensional hydrogen-bonding
      network of O-H...O and N-H...O interactions is observed in the crystal structure
      of (I).H(2)O, similar to the other two solvates, but because of the presence of
      different solvents the three crystal structures have diverse packing motifs. All
      three solvatomorphs are additionally stabilized by nonclassical weak C-H...O
      contacts.

PMID- 23124460
TI  - Supramolecular association in proton-transfer adducts containing benzamidinium
      cations. II. Concomitant polymorphs of the molecular salt of 2,6-dimethoxybenzoic
      acid with benzamidine.
AB  - Two concomitant polymorphs of the molecular salt formed by 2,6-dimethoxybenzoic
      acid, C(9)H(10)O(4) (Dmb), with benzamidine, C(7)H(8)N(2)
      (benzenecarboximidamide, Benzam) from water solution have been identified.
      Benzamidinidium 2,6-dimethoxybenzoate, C(7)H(9)N(2)(+).C(9)H(9)O(4)(-)
      (BenzamH(+).Dmb(-)), was obtained through protonation at the imino N atom of
      Benzam as a result of proton transfer from the acidic hydroxy group of Dmb. In
      the monoclinic polymorph, (I) (space group P2(1)/n), the asymmetric unit consists
      of two Dmb(-) anions and two monoprotonated BenzamH(+) cations. In the
      orthorhombic polymorph, (II) (space group P2(1)2(1)2(1)), one Dmb(-) anion and
      one BenzamH(+) cation constitute the asymmetric unit. In both polymorphic salts,
      the amidinium fragments and carboxylate groups are completely delocalized. This
      delocalization favours the aggregation of the molecular components of these acid
      base complexes into nonplanar dimers with an R(2)(2)(8) graph-set motif via N(+)
      H...O(-) charge-assisted hydrogen bonding. Both the monoclinic and orthorhombic
      forms exhibit one-dimensional isostructurality, as the crystal structures feature
      identical hydrogen-bonding motifs consisting of dimers and catemers.

PMID- 23124461
TI  - 2,4-Dimethyl-1,3-thiazole-5-carboxylic acid: an X-ray structural study at 100 K
      and Hirshfeld surface analysis.
AB  - The crystal structure of the title thiazolecarboxylic acid derivative,
      C(6)H(7)NO(2)S, (I), has been determined from single-crystal X-ray analysis at
      100 K. In the crystal packing, an interplay of O-H...N and C-H...O hydrogen bonds
      connects the molecules to form C(6)R(2)(2)(8) polymeric chains, which are further
      linked via weak C-H...O hydrogen bonds into a two-dimensional supramolecular
      framework. The relative contributions of different interactions to the Hirshfeld
      surface in (I) and a few related thiazolecarboxylic acid derivatives indicate
      that the H...H, N...H and O...H contacts can account for about 50-70% of the
      total Hirshfeld surface area in this class of compound.

PMID- 23124462
TI  - Felodipine-diazabicyclo[2.2.2]octane-water (1/1/1).
AB  - The title compound, C(18)H(19)Cl(2)NO(4).C(6)H(12)N(2).H(2)O, is a cocrystal
      hydrate containing the active pharmaceutical ingredient felodipine and
      diazabicyclo[2.2.2]octane (DABCO). The DABCO and water molecules are linked
      through O-H...N hydrogen bonds into chains around 2(1) screw axes, while the
      felodipine molecules form N-H...O hydrogen bonds to the water molecules. The
      felodipine molecules adopt centrosymmetric back-to-back arrangements that are
      similar to those present in all of its four reported polymorphs. The
      dichlorophenyl rings also form pi-stacking interactions. The inclusion of water
      molecules in the cocrystal, rather than formation of N-H...N hydrogen bonds
      between felodipine and DABCO, may be associated with steric hindrance that would
      arise between DABCO and the methyl groups of felodipine if they were directly
      involved in hydrogen bonding.

PMID- 23124463
TI  - Sulfonate pseudohalides of boron subphthalocyanine.
AB  - The crystal structures of three sulfonate pseudohalide derivatives of boron
      subphthalocyanine (BsubPc) are described and compared with four structures of
      three published sulfonate derivatives. Benzenesulfonate boron subphthalocyanine
      [(benzenesulfonato)(subphthalocyaninato)boron, C(30)H(17)BN(6)O(3)S, (I)]
      crystallizes in the space group P-1 with Z = 2. The structure contains two
      centrosymmetric pi-stacking interactions between the concave faces of the
      isoindoline units in the BsubPc ligands. 3-Nitrobenzenesulfonate boron
      subphthalocyanine [(3-nitrobenzenesulfonato)(subphthalocyaninato)boron,
      C(30)H(16)BN(7)O(5)S, (II)] crystallizes in the space group P2(1)/c with Z = 4.
      The structure contains an intermolecular S-O...pi interaction from the sulfonate
      group to a five-membered N-containing ring of an isoindoline unit on the concave
      side of a neighbouring BsubPc ligand, at a distance of 3.151 (3) A. The crystal
      of methanesulfonate boron subphthalocyanine
      [(methanesulfonato)(subphthalocyaninato)boron, C(25)H(15)BN(6)O(3)S, (III)] was
      produced via sublimation and it is not a solvate, in contrast with two previously
      published structures of the same compound. Compound (III) crystallizes in the
      space group P2(1)/n with Z = 2, and its structure is similar to that of the more
      common compound Cl-BsubPc.

PMID- 23124464
TI  - Tetranaphthyleno[5,6-bcd:11,12-b'c'd':17,18-b''c''d'':23,24
      b'''c'''d''']tetrafuran.
AB  - The title compound, C(40)H(16)O(4) or [C(10)H(4)O](4), is a planar tetrameric
      cyclooligomer which crystallizes in the monoclinic space group P2(1)/n. The
      compound is located on an inversion center with the asymmetric unit consisting of
      half of the molecule. The compound displays an interesting packing structure,
      where the cyclooligomer displays both layered packing with respect to nearest
      neighbors and a rotation of adjacent planar rings that results in additional
      interactions. The geometric parameters of the compound agree well with those of
      comparable cyclooligomers, while the packing reveals some similarities and
      differences.

PMID- 23124465
TI  - (Z)-5-[(5-Methyl-1H-imidazol-4-yl)methylidene]-2-sulfanylidene-1,3-thiazolidin-4
      one monohydrate: a three-dimensional hydrogen-bonded framework structure.
AB  - The non-H atoms in the organic component of the title compound,
      C(8)H(7)N(3)OS(2).H(2)O, are almost coplanar, as the dihedral angle between the
      two ring planes is only 1.8 (2) degrees ; there is a wide C-C-C angle of 127.8
      (3) degrees  at the methine C atom linking the two rings. The molecular
      components are linked into a three-dimensional framework structure by two-centre
      hydrogen bonds of N-H...O and O-H...N types, together with a three-centre O
      H...(N,S) system. Comparisons are made with some (Z)-5-arylmethylidene-2
      sulfanylidene-1,3-thiazolidin-4-ones.

PMID- 23124466
TI  - {5'-O-[Bis(4-methoxyphenyl)(phenyl)methyl]-2'-deoxy-beta-D
      threopentofuranosyl}thymine ethyl acetate 0.25-solvate.
AB  - The title compound, C(31)H(32)N(2)O(7).0.25C(4)H(8)O(2), is a key intermediate in
      the synthesis of [(18)F]fluorine-labelled thymidine ((18)F-FLT), which is the
      most widely used molecular imaging probe for positron emission tomography (PET).
      The crystallographic asymmetric unit contains two independent thymine molecules
      plus one partially occupied site for an ethyl acetate molecule. The two
      independent thymine molecules show similar geometrical features, except that the
      dimethoxytrityl groups adopt different orientations with respect to the remainder
      of the molecule. Each thymine base adopts an anti conformation with respect to
      the attached deoxyribose ring, and the deoxyribose rings show C3-endo puckering.
      The conformation of the side chain at the C1 position of the deoxyribose ring is
      gauche+. Intermolecular N-H...O and O-H...O hydrogen bonds link the molecules
      into one-dimensional chains.

PMID- 23124467
TI  - Three novel benzothiazine-fused triazoles as potential centrally acting muscle
      relaxants.
AB  - The structures of the novel triazolobenzothiazines 2,4-dihydro-1H
      benzo[b][1,2,4]triazolo[4,3-d][1,4]thiazin-1-one (IDPH-791), C(9)H(7)N(3)OS, (I),
      a potential muscle relaxant, its benzoyl derivative, 2-(2-oxo-2-phenylethyl)-2,4
      dihydro-1H-benzo[b][1,2,4]triazolo[4,3-d][1,4]thiazin-1-one, C(20)H(17)N(3)O(4)S,
      (II), and the beta-keto ester derivative, ethyl 3-oxo-2-(1-oxo-2,4-dihydro-1H
      benzo[b][1,2,4]triazolo[4,3-d][1,4]thiazin-2-yl)-3-phenylpropanoate,
      C(17)H(13)N(3)O(2)S, (III), are the first examples of benzothiazine-fused
      triazoles in the crystallographic literature. The heterocyclic thiazine rings in
      all three structures adopt a distorted half-chair conformation. Compound (III)
      exists in the trans-beta-diketo form. Other than N-H...O hydrogen bonds in (I)
      forming dimers, no formal intermolecular hydrogen bonds are involved in the
      crystal packing of any of the three structures, which is dominated by C-H...O/N
      and pi-pi stacking interactions.

PMID- 23124468
TI  - Supramolecular sheets in (4H-chromeno[4,3-c]isoxazol-3-yl)methanol and its
      hydrated 8-methyl-substituted analogue at 100 K.
AB  - The title compounds, (4H-chromeno[4,3-c]isoxazol-3-yl)methanol, C(11)H(9)NO(3),
      (I), and (8-methyl-4H-chromeno[4,3-c]isoxazol-3-yl)methanol monohydrate,
      C(12)H(11)NO(3).H(2)O, (II), crystallize in the monoclinic space groups P2(1)/c
      and C2/c, respectively. The simple addition of a methyl substituent in (II)
      results in a change in the structure type and substantially alters the
      intermolecular interaction patterns, while retaining the point-group symmetry
      2/m. Compound (II) crystallizes as a hydrate and the resulting hydrogen-bonding
      interactions involving the water molecule are the cause of differences in the
      hydrogen-bonded supramolecular motifs present in (I) and (II). The water molecule
      in (II) is disordered over two positions having very similar orientations, with
      occupancies of 0.571 (18) and 0.429 (18), although the pattern of hydrogen
      bonding interactions for the two disordered water molecules remains essentially
      the same. In both compounds, the primary donor hydroxy group adopts a trans
      conformation with respect to the isoxazole O atom, with a torsion angle of 170.65
      (8) degrees  for (I) and 179.56 (10) degrees  for (II), the small difference
      being due to differences in the hydrogen-bonding environment of the hydroxy
      group. In (I), molecules are linked through two independent O-H...N and C-H...O
      hydrogen bonds and form sheets of centrosymmetric R(4)(4)(18) and R(4)(4)(14)
      rings extending parallel to the (100) plane. The supramolecular motifs in (II)
      generate two-dimensional sheets parallel to the (100) plane through a combination
      of O-H...X (X = N, O) and C-H...O hydrogen bonds, leading to water-assisted
      noncentrosymmetric R(2)(2)(8) and R(6)(6)(20) motifs. The present work is an
      example of how the simple replacement of a substituent in the main molecular
      scaffold may transform the structure type, paving the way for a variety of
      supramolecular motifs and consequently altering the complexity of the
      intermolecular interaction patterns.

PMID- 23124469
TI  - Of [Hamsters] and men: a new perspective on host cell proteins.

PMID- 23124470
TI  - Enrichment of carbon dioxide in the atmosphere increases the capsaicinoids
      content in Habanero peppers (Capsicum chinense Jacq.).
AB  - BACKGROUND: The effects of the increase of atmospheric CO2 on agricultural
      productivity have been mainly analyzed through its impact on biomass yield, and
      little attention has been directed to quality traits, such as nutritional or
      organoleptic attributes. For this study, plants of hot Habanero pepper (Capsicum
      chinense Jacq.) were grown in growth chambers under three different CO2 levels:
      380 (normal atmospheric value), 760 and 1140 umol mol(-1), and their effects on
      pod yield, size, color and pungency, were monitored. RESULTS: The total number of
      pods per plant increased by 88.5% at the highest CO2 , in comparison to plants
      grown at normal CO2 conditions. Pod size and yield per plant also increased when
      plants were grown at the highest CO2 concentration (partial pressure).
      Furthermore, total capsaicinoids contents in ripe peppers under a high CO2
      atmosphere were 27% higher than those from plants under lower concentrations, but
      it was not the case for immature pods. CONCLUSION: These data suggest that the
      increase of atmospheric CO2 could modify specific routes of secondary metabolism
      as well as others desirable traits, thus affecting the quality of Capsicum pepper
      products.

PMID- 23124471
TI  - In vitro antifungal activity of sanguinarine and chelerythrine derivatives
      against phytopathogenic fungi.
AB  - In order to understand the antifungal activity of some derivatives of
      sanguinarine (S) and chelerythrine (C) and their structure-activity
      relationships, sixteen derivatives of S and C were prepared and evaluated for in
      vitro antifungal activity against seven phytopathogenic fungi by the mycelial
      growth rate method. The results showed that S, C and their 6-alkoxy dihydro
      derivatives S1-S4, C1-C4 and 6-cyanodihydro derivatives S5, C5 showed significant
      antifungal activity at 100 ug/mL against all the tested fungi. For most tested
      fungi, the median effective concentrations of S, S1, C and C1 were in a range of
      14-50 ug/mL. The structure-activity relationship showed that the C=N+ moiety was
      the determinant for the antifungal activity of S and C. S1-S5 and C1-C5 could be
      considered as the precursors of S and C, respectively. Thus, the present results
      strongly suggested that S and C or their derivatives S1-S5 and C1-C5 should be
      considered as good lead compounds or model molecules to develop new anti
      phytopathogenic fungal agents. can't login to work station for 2hrs--took 2 hrs
      vacation

PMID- 23124472
TI  - A facile synthesis of 5'-fluoro-5'-deoxyacadesine (5'-F-AICAR): a novel non
      phosphorylable AICAR analogue.
AB  - The substitution of a hydroxyl group by a fluorine atom in a potential drug is an
      efficient reaction that can, in principle, improve its pharmacological
      properties. Herein,  the synthesis of the novel compound 5'-fluoro-5'
      deoxyacadesine (5'-F-AICAR), a strict analogue of AICAR that cannot be 5'
      phosphorylated to ZMP by cellular kinases, is reported.

PMID- 23124473
TI  - Sol-gel entrapped Candida antarctica lipase B--a biocatalyst with excellent
      stability for kinetic resolution of secondary alcohols.
AB  - Sol-gel entrapment is an efficient immobilization technique that allows
      preparation of robust and highly stable biocatalysts. Lipase from Candida
      antarctica B was immobilized by sol-gel entrapment and by sol-gel entrapment
      combined with adsorption on Celite 545, using a ternary silane precursor system.
      After optimization of the immobilization protocol, the best enzyme loading was
      17.4 mg/g support for sol-gel entrapped lipase and 10.7 mg/g support for samples
      obtained by entrapment and adsorption. Sol-gel immobilized enzymes showed
      excellent values of enantiomeric ratio E and activity when ionic liquid 1-octyl-3
      methyl-imidazolium tetrafluoroborate was used as additive. Immobilization
      increased the stability of the obtained biocatalysts in several organic solvents.
      Excellent operational stability was obtained for the immobilized lipase,
      maintaining unaltered catalytic activity and enantioselectivity during 15 reuse
      cycles.  The biocatalysts were characterized using scanning electron microscopy
      (SEM) and fluorescence microscopy. The improved catalytic efficiency of entrapped
      lipases recommends their application for large-scale kinetic resolution of
      optically active secondary alcohols.

PMID- 23124474
TI  - Phosphane-based cyclodextrins as mass transfer agents and ligands for aqueous
      organometallic catalysis.
AB  - The replacement of hazardous solvents and the utilization of catalytic processes
      are two key points of the green chemistry movement, so aqueous organometallic
      catalytic processes are of great interest in this context. Nevertheless, these
      processes require not only the use of water-soluble ligands such as phosphanes to
      solubilise the transition metals in water, but also the use of mass transfer
      agents to increase the solubility of organic substrates in water. In this
      context, phosphanes based on a cyclodextrin skeleton are an interesting
      alternative since these compounds can simultaneously act as mass transfer agents
      and as coordinating species towards transition metals. For twenty years, various
      cyclodextrin-functionalized phosphanes have been described in the literature.
      Nevertheless, while their coordinating properties towards transition metals and
      their catalytic properties were fully detailed, their mass transfer agent
      properties were much less discussed. As these mass transfer agent properties are
      directly linked to the availability of the cyclodextrin cavity, the aim of this
      review is to demonstrate that the nature of the reaction solvent and the nature
      of the linker between cyclodextrin and phosphorous moieties can deeply influence
      the recognition properties. In addition, the impact on the catalytic activity
      will be also discussed.

PMID- 23124475
TI  - Three novel functional polymorphisms in the promoter of FGFR2 gene and breast
      cancer risk: a HuGE review and meta-analysis.
AB  - Published data on the association between three novel functional polymorphisms
      (rs11200014, rs2981579, and rs2981578) in the promoter of FGFR2 gene and breast
      cancer risk are inconclusive. The aim of this human genome epidemiology review
      and meta-analysis was to derive a more precise estimation of the relationship. A
      literature search of Pubmed, Embase, Web of science, and CBM databases from
      inception through July 2012 was conducted. Seventeen studies were included with a
      total of 21,742 breast cancer cases and 31,125 healthy controls. Crude odds
      ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the
      strength of association in allele model, dominant model, recessive model,
      homozygous model, and heterozygous model. When all the eligible studies were
      pooled into the meta-analysis, remarkable associations between the rs11200014
      (A>G) polymorphism and breast cancer risk were detected in Caucasians (G vs. A:
      OR = 1.28, 95 % CI: 1.21-1.35; GG/AG vs. AA: OR = 1.32, 95 % CI: 1.18-1.48), but
      not in Asians and Africans. In addition, there were statistically significant
      associations between the rs2981579 (G>A) polymorphism and increased risk of
      breast cancer risk in all ethnicities (A vs. G: OR = 1.20, 95 % CI: 1.11-1.29;
      AA/GA vs. GG: OR = 1.32, 95 % CI: 1.18-1.48; AA vs. GG: OR = 1.67, 95 % CI: 1.55
      1.81), including Caucasians, Asians, and Africans. However, the TT genotype of
      rs2981578 (C>T) polymorphism might decrease breast cancer risk (TT vs. CC/CT: OR
      = 0.55, 95 % CI: 0.38-0.79; TT vs. CC: OR = 0.51, 95 % CI: 0.35-0.76; TT vs. CT:
      OR = 0.58, 95 % CI: 0.40-0.85), especially among Asians. Results from the current
      meta-analysis indicates that three novel functional polymorphisms (rs11200014,
      rs2981579, and rs2981578) in the promoter of FGFR2 gene are associated with
      breast cancer susceptibility and might be a potential biomarkers for breast
      cancer risk.

PMID- 23124477
TI  - Cleft lip, cleft palate, hereditary diffuse gastric cancer and germline mutations
      in CDH1.

PMID- 23124476
TI  - Clinical and biologic features of triple-negative breast cancers in a large
      cohort of patients with long-term follow-up.
AB  - Studies on well characterized, large populations of estrogen receptor
      (ER)/progesterone receptor (PgR)/HER2-negative [triple-negative (TN)] breast
      cancer (BC) patients with long-term follow-up are lacking. In this study, we
      analyze clinical outcomes of TN BC and implications of epidermal growth factor
      receptor (EGFR) expression. Clinical and biologic features, time to first
      recurrence (TTFR), and overall survival (OS) were compared in 253 TN versus 1,036
      ER positive, PgR positive, HER2-negative [estrogen-driven (ED)] BC. Compared to
      ED, TN tumors were larger (p = 0.02), more proliferative (high S-phase 54 vs. 17
      %, p < 0.0001), more aneuploid (64 vs. 43 %, p < 0.0001) and more likely EGFR
      positive (>=10 fmol/mg by radioligand-binding assay, 49 vs. 7 %, p < 0.0001).
      Among TN, EGFR-positive BC were larger (p = 0.0018), more proliferative (p <
      0.0001), and more aneuploid, (p < 0.0001) than EGFR-negative BC. Adjuvant-treated
      TN patients had shorter TTFR (p = 0.0003), and OS (p = 0.0017), than ED patients.
      However, in untreated patients, no differences in TTFR and OS were observed at 8
      years median follow-up. Among TN patients, EGFR expression was not associated
      with worse outcome. TN tumors have a worse outcome in systemically treated
      patients but not in untreated patients. EGFR expression, does not predict for
      worse long-term survival.

PMID- 23124478
TI  - Changes in pyriform sinus morphology in the head rotated position as assessed by
      320-row area detector CT.
AB  - In patients with unilateral pharyngeal paresis and dysphagia, the head is rotated
      to the paretic side to prevent food flow to the rotated side during swallowing.
      Only a few studies to date have reported on pyriform sinus morphology upon head
      rotation. The purpose of this study was to measure the volume, depth, and cross
      sectional area of the pyriform sinus during head rotation using 320-row area
      detector computed tomography. We imaged the neck during head rotation at 0
      degrees  and at 30 degrees , 45 degrees , and 60 degrees  to the left or right in
      nine healthy young adults and determined the volume, depth, and cross-sectional
      area of the pyriform sinus in each position. On the rotated side, volume and
      cross-sectional area were significantly decreased at 60 degrees . In contrast,
      volume, cross-sectional area, and depth were all significantly increased on the
      opposite side at 60 degrees . These results suggest that head rotation at 60
      degrees  significantly increases the volume, cross-sectional area, and depth of
      the opposite side, and significantly decreases the volume and depth of the
      rotated side of the pyriform sinus.

PMID- 23124479
TI  - In silico multi-scale model of transport and dynamic seeding in a bone tissue
      engineering perfusion bioreactor.
AB  - Computer simulations can potentially be used to design, predict, and inform
      properties for tissue engineering perfusion bioreactors. In this work, we
      investigate the flow properties that result from a particular poly-L-lactide
      porous scaffold and a particular choice of perfusion bioreactor vessel design
      used in bone tissue engineering. We also propose a model to investigate the
      dynamic seeding properties such as the homogeneity (or lack of) of the cellular
      distribution within the scaffold of the perfusion bioreactor: a pre-requisite for
      the subsequent successful uniform growth of a viable bone tissue engineered
      construct. Flows inside geometrically complex scaffolds have been investigated
      previously and results shown at these pore scales. Here, it is our aim to show
      accurately that through the use of modern high performance computers that the
      bioreactor device scale that encloses a scaffold can affect the flows and
      stresses within the pores throughout the scaffold which has implications for
      bioreactor design, control, and use. Central to this work is that the boundary
      conditions are derived from micro computed tomography scans of both a device
      chamber and scaffold in order to avoid generalizations and uncertainties. Dynamic
      seeding methods have also been shown to provide certain advantages over static
      seeding methods. We propose here a novel coupled model for dynamic seeding
      accounting for flow, species mass transport and cell advection-diffusion
      attachment tuned for bone tissue engineering. The model highlights the timescale
      differences between different species suggesting that traditional homogeneous
      porous flow models of transport must be applied with caution to perfusion
      bioreactors. Our in silico data illustrate the extent to which these experiments
      have the potential to contribute to future design and development of large-scale
      bioreactors.

PMID- 23124480
TI  - Mental health of internally displaced preschool children: a cross-sectional study
      conducted in Bogota, Colombia.
AB  - PURPOSE: Ongoing armed conflicts, like the one in Colombia, have forcibly
      displaced millions of people including many young children. This study aimed to
      assess the mental health of internally displaced preschoolers in Bogota Colombia
      and to identify correlates of mental health in these children. METHODS: Cross
      sectional study conducted among 279 children attending four kindergartens in a
      deprived neighbourhood in Bogota. Child mental health was assessed with the Child
      Behaviour Checklist (CBCL) 1.5-5 years, a parent-report. Univariate analyses and
      multivariate logistic regressions were performed to assess the association
      between displacement and child mental health and to identify correlates of mental
      health in displaced children. RESULTS: Displaced children (n = 90) more often met
      borderline cut-off scores for the CBCL scales than non-displaced children (n =
      189) (e.g. total problems 46.7 vs. 22.8 %; p < 0.001). The association between
      displacement and presence of CBCL total problems remained after adjustment for
      socio-demographic factors (Adjusted OR 3.3, 95 % CI 1.5; 6.9). Caretaker's mental
      health partly explained the association. In displaced children, caretaker's
      mental health (p < 0.01) and family functioning (p < 0.01) were independently
      associated with child mental health. Exposure to traumatic events and social
      support was also associated with child mental health; however, associations were
      not independent. CONCLUSION: In this deprived neighbourhood in Bogota, preschool
      children registered as internally displaced presented worse mental health than
      non-displaced peers. Family functioning and caretaker's mental health were
      strongly and independently associated with displaced children's mental health.

PMID- 23124481
TI  - Evaluation of a campaign to improve awareness and attitudes of young people
      towards mental health issues.
AB  - PURPOSE: This study evaluated the effectiveness of the In One Voice campaign for
      raising mental health awareness and improving attitudes of youth and young adults
      towards mental health issues. The campaign featured a prominent male sports
      figure talking about mental health issues and used online social media. METHODS:
      A successive independent samples design assessed market penetration and
      attitudinal changes among the young people. Two samples completed an online
      questionnaire either immediately before (T1: n = 403) or 2 months after (T2: n =
      403) the campaign launch. Website analytics determined changes in activity levels
      of a youth-focused mental health website (mindcheck.ca). RESULTS: One-quarter
      (24.8 %, n = 100) of the respondents remembered the campaign. The proportion of
      respondents who were aware of the website increased significantly from 6.0 % at
      T1 to 15.6 % at T2. Average overall scores on standardized measures of personal
      stigma and social distance were not significantly different between T1 and T2
      respondents. Attitudes towards mental health issues were statistically similar
      between respondents who were or were not exposed to the campaign. Those who were
      exposed to the campaign were significantly more likely to talk about and seek
      information relating to mental health issues. CONCLUSIONS: The proximal outcomes
      of the campaign to increase awareness and use of the website were achieved. The
      distal outcome of the campaign to improve attitudes towards mental health issues
      was not successfully achieved. The brief social media campaign improved mental
      health literacy outcomes, but had limited effect on personal stigma and social
      distance.

PMID- 23124482
TI  - Public attitudes towards people with depression in times of uncertainty: results
      from three population surveys in Germany.
AB  - PURPOSE: The recent increase of so-called precarious work conditions plus the
      current financial crisis have led to a growing sense of uncertainty among the
      public. This may have repercussions on attitudes towards people with mental
      illness. Particularly, the public may have become more reluctant to support
      access to work for these people. METHODS: In 1990, 2001 and 2011, population
      surveys were conducted in the "old" states of Germany, using the same sampling
      procedure, interview mode and measures. Within the context of a fully structured
      interview respondents were presented a case-vignette depicting a person with
      symptoms of depression. They were then asked how willing they would be to accept
      the person in the vignette in various social relationships. RESULTS: While the
      German public's unwillingness to recommend an individual with depression for a
      job remained unchanged during the 1990s, it increased significantly during the
      subsequent decade. By contrast, in all other social relationships studied, no
      increase of the desire for social distance could be observed during this time
      period. The trend towards withholding access to jobs was most pronounced among
      employed respondents. CONCLUSIONS: The results of our study underline the
      importance of macro-social factors for the discrimination of people with mental
      illness.

PMID- 23124484
TI  - Statistical multi-path exposure method for assessing the whole-body SAR in a
      heterogeneous human body model in a realistic environment.
AB  - Assessing the whole-body absorption in a human in a realistic environment
      requires a statistical approach covering all possible exposure situations. This
      article describes the development of a statistical multi-path exposure method for
      heterogeneous realistic human body models. The method is applied for the 6-year
      old Virtual Family boy (VFB) exposed to the GSM downlink at 950 MHz. It is shown
      that the whole-body SAR does not differ significantly over the different
      environments at an operating frequency of 950 MHz. Furthermore, the whole-body
      SAR in the VFB for multi-path exposure exceeds the whole-body SAR for worst-case
      single-incident plane wave exposure by 3.6%. Moreover, the ICNIRP reference
      levels are not conservative with the basic restrictions in 0.3% of the exposure
      samples for the VFB at the GSM downlink of 950 MHz. The homogeneous spheroid with
      the dielectric properties of the head suggested by the IEC underestimates the
      absorption compared to realistic human body models. Moreover, the variation in
      the whole-body SAR for realistic human body models is larger than for homogeneous
      spheroid models. This is mainly due to the heterogeneity of the tissues and the
      irregular shape of the realistic human body model compared to homogeneous
      spheroid human body models.

PMID- 23124483
TI  - Correlation of telomere length shortening with TP53 somatic mutations,
      polymorphisms and allelic loss in breast tumors and esophageal cancer.
AB  - Genomic instability caused by telomere erosion is an important mechanism of
      tumorigenesis. p53 plays a key role in cellular senescence and/or apoptosis
      associated with telomere erosion which positions p53 as a guard against
      tumorigenesis. The present study was undertaken to investigate the potential
      interactions between p53 functional mutations, polymorphisms, allelic loss and
      telomere erosion in 126 breast tumor patients and 68 esophageal cancer patients.
      Telomere length (TL) was measured by real-time quantitative PCR. Somatic
      mutations, polymorphisms and allelic loss in the TP53 gene were detected by
      direct sequencing of both tumor and normal tissue samples. Our results showed
      that telomeres were significantly shorter in tumors with somatic p53 mutations
      compared with tumors with wild-type p53 in both breast tumors (P=0.007) and
      esophageal cancer (P=0.001). Telomeres of patients with minor genotype CC of
      rs12951053 and GG of rs1042522 were significantly shorter compared to patients
      with other genotypes of this single nucleotide polymorphism in esophageal cancer
      tissue. Furthermore, TP53 allelic loss was detected and significantly associated
      with somatic mutations in both types of tumor tissues. These findings suggest
      that somatic p53 mutations, rs12951053 genotype CC and rs1042522 genotype GG
      contribute to erosion of telomeres, and TP53 allelic loss may be one of the
      representations of chromosomal instability caused by telomere erosion combined
      with somatic p53 mutations. These results support that the TP53 gene has a strong
      interaction with TL erosion in tumorigenesis.

PMID- 23124486
TI  - Migralepsy: a new case confirming the existence of this migraine complication and
      proposing therapy.

PMID- 23124485
TI  - Influence of intra- and extracellular acidification on free radical formation and
      mitochondria membrane potential in rat brain synaptosomes.
AB  - Brain ischemia is accompanied by lowering of intra- and extracellular pH. Stroke
      often leads to irreversible damage of synaptic transmission by unknown mechanism.
      We investigated an influence of lowering of pH(i) and pH(o) on free radical
      formation in synaptosomes. Three models of acidosis were used: (1) pH(o) 6.0
      corresponding to pH(i) decrease down to 6.04; (2) pH(o) 7.0 corresponding to the
      lowering of pH(i) down to 6.92: (3) 1 mM amiloride corresponding to pH(i)
      decrease down to 6.65. We have shown that both types of extracellular
      acidification, but not intracellular acidification, increase 2',7'
      dichlorodihydrofluorescein diacetate fluorescence that reflects free radical
      formation. These three treatments induce the rise of the dihydroethidium
      fluorescence that reports synthesis of superoxide anion. However, the impact of
      amiloride on superoxide anion synthesis was less than that induced by moderate
      extracellular acidification. Superoxide anion synthesis at pH(o) 7.0 was almost
      completely eliminated by mitochondrial uncoupler carbonyl cyanide 4
      (trifluoromethoxy)phenylhydrazone. Furthermore, using fluorescent dyes JC-1 and
      rhodamine-123, we confirmed that pH(o) lowering, but not intracellular
      acidification, led to depolarization of intrasynaptosomal mitochondria. We have
      shown that pH(o) but not pH(i) lowering led to oxidative stress in neuronal
      presynaptic endings that might underlie the long-term irreversible changing in
      synaptic transmission.

PMID- 23124487
TI  - Septo-optic dysplasia plus bilateral perisylvian polymicrogyria: a case report.

PMID- 23124488
TI  - Aseptic meningitis in Kikuchi's disease mimicking tuberculous meningitis.

PMID- 23124489
TI  - Derivatives in discrete mathematics: a novel graph-theoretical invariant for
      generating new 2/3D molecular descriptors. I. Theory and QSPR application.
AB  - In this report, we present a new mathematical approach for describing chemical
      structures of organic molecules at atomic-molecular level, proposing for the
      first time the use of the concept of the derivative ([Formula: see text]) of a
      molecular graph (MG) with respect to a given event (E), to obtain a new family of
      molecular descriptors (MDs). With this purpose, a new matrix representation of
      the MG, which generalizes graph's theory's traditional incidence matrix, is
      introduced. This matrix, denominated the generalized incidence matrix, Q, arises
      from the Boolean representation of molecular sub-graphs that participate in the
      formation of the graph molecular skeleton MG and could be complete (representing
      all possible connected sub-graphs) or constitute sub-graphs of determined orders
      or types as well as a combination of these. The Q matrix is a non-quadratic and
      unsymmetrical in nature, its columns (n) and rows (m) are conditions (letters)
      and collection of conditions (words) with which the event occurs. This non
      quadratic and unsymmetrical matrix is transformed, by algebraic manipulation, to
      a quadratic and symmetric matrix known as relations frequency matrix, F, which
      characterizes the participation intensity of the conditions (letters) in the
      events (words). With F, we calculate the derivative over a pair of atomic nuclei.
      The local index for the atomic nuclei i, Delta(i), can therefore be obtained as a
      linear combination of all the pair derivatives of the atomic nuclei i with all
      the rest of the j's atomic nuclei. Here, we also define new strategies that
      generalize the present form of obtaining global or local (group or atom-type)
      invariants from atomic contributions (local vertex invariants, LOVIs). In respect
      to this, metric (norms), means and statistical invariants are introduced. These
      invariants are applied to a vector whose components are the values Delta(i) for
      the atomic nuclei of the molecule or its fragments. Moreover, with the purpose of
      differentiating among different atoms, an atomic weighting scheme (atom-type
      labels) is used in the formation of the matrix Q or in LOVIs state. The obtained
      indices were utilized to describe the partition coefficient (Log P) and the
      reactivity index (Log K) of the 34 derivatives of 2-furylethylenes. In all the
      cases, our MDs showed better statistical results than those previously obtained
      using some of the most used families of MDs in chemometric practice. Therefore,
      it has been demonstrated to that the proposed MDs are useful in molecular design
      and permit obtaining easier and robust mathematical models than the majority of
      those reported in the literature. All this range of mentioned possibilities open
      "the doors" to the creation of a new family of MDs, using the graph derivative,
      and avail a new tool for QSAR/QSPR and molecular diversity/similarity studies.

PMID- 23124490
TI  - Identification of flavonoids with trypsin inhibitory activity extracted from
      orange peel and green tea leaves.
AB  - BACKGROUND: Orange peel (Citrus sinensis) and green tea (Camellia sinensis)
      leaves, rich sources of food flavonoids, were analyzed for their trypsin
      inhibitory potential. Hesperetin, rutin and hesperidin from orange peel, and
      catechin from green tea leaves, were isolated and their chemical structures were
      analyzed. All four compounds were evaluated for their trypsin inhibitory
      potential. RESULTS: Among all the isolated compounds, rutin exhibited the highest
      protease inhibition activity (75.4 +/- 0.9%) with IC50 = 16 +/- 2 umol L(-1),
      followed by catechin (65.3 +/- 1.4%; IC50 = 83 +/- 9 umol L(-1)), hesperetin
      (62.1 +/- 1.3%; IC50 = 104 +/- 12 umol L(-1)) and hesperidin (59.7 +/- 1.1%; IC50
      = 127 +/- 14 umol L(-1)). Lineweaver-Burk and Dixon plots and their secondary
      replots indicated that all four compounds possessed non-competitive inhibition.
      The Ki values of hesperetin, rutin, hesperidin and catechin were calculated as
      90.2 +/- 1.1, 17.5 +/- 0.6, 84.2 +/- 1.5 and 65.1 +/- 1.5 umol L(-1)
      respectively. CONCLUSION: The present results suggest that the four isolated
      flavonoids can be used as a supplement in food for the treatment of pathologies
      associated with the degradation of a specific protein.

PMID- 23124491
TI  - Three to seven year follow-up of a tapered modular femoral prosthesis in revision
      total hip arthroplasty.
AB  - PURPOSE: Modular femoral prostheses can provide independent distal fixation and
      intraoperative flexibility and are being used increasingly, especially in
      patients with proximal femoral bone defects. This retrospective clinical study
      evaluated whether modular prostheses were effective and reliable implants for
      femoral revision. METHOD: This case series consisted of 58 patients who underwent
      hip revision with a tapered modular femoral prosthesis at our institution between
      2004 and 2008. Mean patient age at surgery was 64 years (range 18-86 years).
      Femoral bone defects before revision surgery were evaluated using the Paprosky
      classification. All patients were followed for a minimum of 3 years (mean 4.3
      years, range 3-7 years) with clinical and radiographic evaluation. Re-revisions
      and complications were also recorded. RESULTS: Two stems required re-revision,
      one each for recurrent deep infection and periprosthetic fracture. At last follow
      up, the Harris Hip Score and Visual Analog Pain Scores had improved
      significantly, the median radiographic stem migration was 1.6 mm, leg length
      discrepancy was corrected in 64 % of the patients and osseointegration occurred
      in 90 %. Complications included intraoperative fracture in 10 (17 %) patients and
      hip dislocation in 2 (3 %). CONCLUSION: Modular femoral components can improve
      hip function, provide distal fixation, equalize leg length, and result in fewer
      complications when used to revise failed femoral components.

PMID- 23124492
TI  - Treatment of periprosthetic tibial plateau fractures in unicompartmental knee
      arthroplasty: plates versus cannulated screws.
AB  - INTRODUCTION: Periprosthetic tibial plateau fractures (TPF) are rare but
      represent a serious complication in unicompartmental knee arthroplasty. The most
      common treatment for these fractures is osteosynthesis with cannulated screws or
      plates. The aim of this study was to evaluate two different treatment options for
      periprosthetic fractures. The hypothesis was that angle-stable plates show
      significantly higher fracture loads than fixation with cannulated screws.
      MATERIALS AND METHODS: Twelve matched, paired fresh-frozen tibiae with
      periprosthetic TPF were used for this study. In Group A, osteosyntheses with
      cannulated screws were performed, whereas in Group B plates fixated the
      periprosthetic fracture. DEXA bone density measurement and standard X-rays (AP
      and lateral) were performed before loading the tibiae under standardised
      conditions with a maximum load of up to 10.0 kN. After the specimens had been
      loaded, fracture patterns and fracture loads were analysed and correlated with
      BMD, BMI, bodyweight (BW), age and size of the tibial implant. RESULTS: In the
      plate group all tibiae fracture occured with a median load of F (max) = 2.64
      (0.45-5.68) kN, whereas in the group with cannulated screws fractures occurred at
      a mean load of F (max) = 1.50 (0.27-3.51) kN. The difference was statistically
      significant at p < 0.05. DISCUSSION: Angle-stable plates showed significantly
      higher fracture loads than fixation with cannulated screws. Cannulated screws
      show a reduced stability of the tibial plateau. Therefore in periprosthetic TPF,
      osteosyntheses with angle-stable plates should be recommended instead of
      cannulated screws.

PMID- 23124493
TI  - A porous Sm(III) coordination nanotube with hydrophobic and hydrophilic channels.
AB  - The pi-pi stacking interactions between tptz units from adjacent
      Sm(tptz)(HCOO)(3) coordination nanotubes leads to additional 1D channels (tptz =
      2,4,6-tris(2-pyridyl)-s-triazine). The present compound is a rare case of a
      tubular porous material with both hydrophobic and hydrophilic channels. Permanent
      porosity was confirmed by N(2) adsorption isotherms.

PMID- 23124494
TI  - Journal of Health Care for the Poor and Underserved. Introduction.

PMID- 23124495
TI  - Development of the polio vaccine: a historical perspective of Tuskegee
      University's role in mass production and distribution of HeLa cells.

PMID- 23124496
TI  - The prostate cancer screening controversy: addressing bioethical concerns at a
      community health promotion event for men.
AB  - There are bioethical concerns related to prostate cancer screening. A new
      prostate cancer screening approach at a community health promotion event used
      vouchers to promote informed decision-making in order to reduce these concerns.

PMID- 23124497
TI  - Tuskegee University experience challenges conventional wisdom: is integrative
      bioethics practice the new ethics for the public's health?
AB  - The Tuskegee University National Center for Bioethics in Research and Health Care
      was established in 1999 in partial response to the Presidential Apology for the
      United States Public Health Service's Study of Untreated Syphilis in the Negro
      Male conducted in Macon County, Alabama, from 1932 to 1972. The Center's mission
      of promoting equity and justice in health and health care for African Americans
      and other underserved populations employs an integrative bioethics approach
      informed by moral vision. Etymological and historical analyses are used to
      delineate the meaning and evolution of bioethics and to provide a basis for
      Tuskegee's integrative bioethics niche. Unlike mainstream bioethics, integrative
      bioethics practice is holistic in orientation, and more robust for understanding
      the epistemic realities of minority life, health disparities, and population
      health. The conclusion is that integrative bioethics is relevant to the survival
      of all people, not just a privileged few; it could be the new ethics for the
      public's health.

PMID- 23124499
TI  - HPV, oropharyngeal cancer, and the role of the dentist: a professional ethical
      approach.
AB  - Human papillomavirus (HPV) is an emerging risk factor for oropharyngeal cancer,
      especially among younger patients, and must be thoughtfully addressed by the
      dental community. The professional ethical decision-making model first advanced
      by Ozar and Sokol for use by dentists at chairside (define the dilemma, assess
      the facts, identify and rank the alternatives, and choose a course of action) was
      modified to delineate clearly inputs, considerations, and feedback loops based on
      what is professionally and ethically at stake in advising patients. As the link
      between HPV and oropharyngeal cancer is established through scientific studies,
      the role of the dentist in primary and secondary prevention will be crucial. In
      the absence of definitive evidence, the professional ethical decision-making
      framework presented here allows dentists to systematically work through available
      alternatives. Ultimately, the role of the dentist is to use discretion in
      choosing a professional and ethical course of action for each patient.

PMID- 23124498
TI  - Individual breast cancer risk assessment in underserved populations: integrating
      empirical bioethics and health disparities research.
AB  - Research suggests that individual breast cancer risk assessment may improve
      adherence to recommended screening and prevention guidelines, thereby decreasing
      morbidity and mortality. Further research on the use of risk assessment models in
      underserved minority populations is critical to informing national public health
      efforts to eliminate breast cancer disparities. However, implementing individual
      breast cancer risk assessment in underserved patient populations raises
      particular ethical issues that require further examination. After reviewing these
      issues, we will discuss how empirical bioethics research can be integrated with
      health disparities research to inform the translation of research findings. Our
      in-progress National Cancer Institute (NCI) funded study, How Do Underserved
      Minority Women Think About Breast Cancer?, conducted in the context of a larger
      study on individual breast cancer risk assessment, is presented as a model.

PMID- 23124500
TI  - Ethics of clear health communication: applying the CLEAN Look approach to
      communicate biobanking information for cancer research.
AB  - Cancer innovations, such as biobanking technologies, are continuously evolving to
      improve our understanding and knowledge about cancer prevention and treatment
      modalities. However, the public receives little communication about biobanking
      and is often unaware about this innovation until asked to donate biospecimens. It
      is the researchers' ethical duty to provide clear communications about biobanking
      and biospecimen research. Such information allows the public to understand
      biobanking processes and facilitates informed decision making about biospecimen
      donation. The aims of this paper are 1) to examine the importance of clear
      communication as an ethical imperative when conveying information about cancer
      innovations and 2) to illustrate the use of an organizing framework, the CLEAN (
      C ulture, L iteracy, E ducation, A ssessment, and N etworking) Look approach for
      creating educational priming materials about the topic of biobanking.

PMID- 23124501
TI  - Sociodemographic differences in fears and mistrust contributing to unwillingness
      to participate in cancer screenings.
AB  - Effective provider-patient relationships are vital for positive patient health
      outcomes. This analysis assessed sociodemographic differences in fears and
      mistrust related to the provider-patient relationship, which may contribute to
      unwillingness to participate in cancer screenings (CSs). The data are from a
      stratified, random-digit dial telephone questionnaire of non-institutionalized
      households in New York, Maryland, and Puerto Rico. Statistically significant
      results indicate that Hispanics, compared with Whites, were nearly two times more
      likely to report that fear of being a "guinea pig" and lacking trust in medical
      people would make them unwilling to participate in CSs. Additionally, those with
      less education were over two times more likely to indicate a fear of being
      embarrassed during the screening would make them unwilling to participate in CSs.
      These results highlight areas where health professionals can improve interactions
      with their patients and be attentive to their fears and/or mistrusts to promote
      CSs utilization.

PMID- 23124502
TI  - Community health workers support community-based participatory research ethics:
      lessons learned along the research-to-practice-to-community continuum.
AB  - Ethical principles of community-based participatory research (CBPR)-
      specifically, community engagement, mutual learning, action-reflection, and
      commitment to sustainability--stem from the work of Kurt Lewin and Paulo Freire.
      These are particularly relevant in cancer disparities research because vulnerable
      populations are often construed to be powerless, supposedly benefiting from
      programs over which they have no control. The long history of exploiting minority
      individuals and communities for research purposes (the U.S. Public Health Service
      Tuskegee Syphilis Study being the most notorious) has left a legacy of mistrust
      of research and researchers. The purpose of this article is to examine
      experiences and lessons learned from community health workers (CHWs) in the 10
      year translation of an educational intervention in the research-to-practice-to
      community continuum. We conclude that the central role played by CHWs enabled the
      community to gain some degree of control over the intervention and its delivery,
      thus operationalizing the ethical principles of CBPR.

PMID- 23124503
TI  - Head and neck cancer disparity in underserved communities: probable causes and
      the ethics involved.
AB  - Head and neck cancers are a cause of morbidity and mortality throughout the
      United States. For low-income, African American men they are one of the leading
      causes of excess cancer deaths: although all racial/ethnic groups suffer from
      these cancers, African American men disproportionately suffer and die from them.
      Low-income communities have increased risks for many adverse health conditions
      because of environmental factors and existing social determinants of health.
      These social determinants often lead to unhealthy life circumstances and
      ineffective coping behaviors. Early detection enhances effective treatment
      options, but such services are limited among African Americans, particularly
      African American men in underserved areas. Not addressing oral cancer because of
      these social conditions reflects unjust and unethical behavior by health care
      professionals. In Atlanta, one high-density, limited-resource area has the
      highest incidence of oral cavity cancers. Health Education, Assessment and
      Leadership (HEAL) was created to address the oral cancer incidence and
      prevalence, an example of a preventable health disparity between this underserved
      region and surrounding communities.

PMID- 23124504
TI  - Tuskegee redux: evolution of legal mandates for human experimentation.
AB  - Human health experiments systematically expose people to conditions beyond the
      boundaries of medical evidence. Such experiments have included legal-medical
      collaboration, exemplified in the U.S. by the Public Health Service (PHS)
      Syphilis Study (Tuskegee). That medical experiment was legal, conforming to
      segregationist protocols and specific legislative authorization which excluded a
      selected group of African Americans from any medical protection from syphilis.
      Subsequent corrective action outlawed unethical medical experiments but did not
      address other forms of collaboration, including PHS submission to laws which may
      have placed African American women at increased risk from AIDS and breast cancer.
      Today, anti-lobbying law makes it a felony for PHS workers to openly challenge
      legally anointed suspension of medical evidence. African Americans and other
      vulnerable populations may thereby face excess risks-not only from cancer, but
      also from motor vehicle crashes, firearm assault, end stage renal disease, and
      other problems-with PHS workers as silent partners.

PMID- 23124505
TI  - Evaluation of the Patient-Reported Outcomes Information System (PROMIS((r)))
      Spanish-language physical functioning items.
AB  - PURPOSE: To evaluate the equivalence of the PROMIS((r)) physical functioning item
      bank by language of administration (English versus Spanish). METHODS: The
      PROMIS((r)) wave 1 English-language physical functioning bank consists of 124
      items, and 114 of these were translated into Spanish. ANALYSIS: Item frequencies,
      means and standard deviations, item-scale correlations, and internal consistency
      reliability were calculated. The IRT assumption of unidimensionality was
      evaluated by fitting a single-factor confirmatory factor analytic model. IRT
      threshold and discrimination parameters were estimated using Samejima's Graded
      Response Model. DIF by language of administration was evaluated. RESULTS: Item
      means ranged from 2.53 (SD = 1.36) to 4.62 (SD = 0.82). Coefficient alpha was
      0.99, and item-rest correlations ranged from 0.41 to 0.89. A one-factor model
      fits the data well (CFI = 0.971, TLI = 0.970, and RMSEA = 0.052). The slope
      parameters ranged from 0.45 ("Are you able to run 10 miles?") to 4.50 ("Are you
      able to put on a shirt or blouse?"). The threshold parameters ranged from -1.92
      ("How much do physical health problems now limit your usual physical activities
      (such as walking or climbing stairs)?") to 6.06 ("Are you able to run 10
      miles?"). Fifty of the 114 items were flagged for DIF based on an R(2) of 0.02 or
      above criterion. The expected total score was higher for Spanish- than English
      language respondents. CONCLUSIONS: English- and Spanish-speaking subjects with
      the same level of underlying physical function responded differently to 50 of 114
      items. This study has important implications in the study of physical functioning
      among diverse populations.

PMID- 23124506
TI  - Joseph S. Weiner and the foundation of post-WW II human biology in the United
      Kingdom.
AB  - Both the United States and the United Kingdom experienced a transformation in the
      science of physical anthropology from the period before World War II until the
      post-war period. In the United States, Sherwood L. Washburn is credited with
      being a leading figure in this transformation. In the United Kingdom, two
      individuals were instrumental in bringing about a similar change in the
      profession. These were Joseph S. Weiner at the University of Oxford and Nigel
      Barnicot at the University of London, with Weiner playing the principal role as
      leader in what Washburn called the "New Physical Anthropology," that is, the
      application of evolutionary theory, the de-emphasis on race classification, and
      the application of the scientific method and experimental approaches to problem
      solving. Weiner's contributions to physical anthropology were broad-based-
      climatic and work physiology, paleoanthropology, and human variation--in what
      became known as human biology in the U.K. and human adaptability internationally.
      This biographical essay provides evidence for the significant influence of J.S.
      Weiner on the post-war development of human biology (biological or physical
      anthropology) inthe U.K.

PMID- 23124507
TI  - Cancer cells preferentially lose small chromosomes.
AB  - Genetic and genomic aberrations are the primary cause of cancer. Chromosome
      missegregation leads to aneuploidy and provides cancer cells with a mechanism to
      lose tumor suppressor loci and gain extra copies of oncogenes. Using cytogenetic
      and array-based comparative genomic hybridization data, we analyzed numerical
      chromosome aneuploidy in 43,205 human tumors and found that 68% of solid tumors
      are aneuploid. In solid tumors, almost all chromosomes are more frequently lost
      than gained with chromosomes 7, 12 and 20 being the only exceptions with more
      frequent gains. Strikingly, small chromosomes are lost more readily than large
      ones, but no such inverse size correlation is observed with chromosome gains.
      Because of increasing levels of proteotoxic stress, chromosome gains have been
      shown to slow cell proliferation in a manner proportional to the number of extra
      gene copies gained. However, we find that the extra chromosome in trisomic tumors
      does not preferentially have a low gene copy number, suggesting that a
      proteotoxicity-mediated proliferation barrier is not sustained during tumor
      progression. Paradoxically, despite a bias toward chromosome loss, gains of
      chromosomes are a poor prognostic marker in ovarian adenocarcinomas. In addition,
      we find that solid and non-solid cancers have markedly distinct whole-chromosome
      aneuploidy signatures, which may underlie their fundamentally different
      etiologies. Finally, preferential chromosome loss is observed in both early and
      late stages of astrocytoma. Our results open up new avenues of enquiry into the
      role and nature of whole-chromosome aneuploidy in human tumors and will redirect
      modeling and genetic targeting efforts in patients.

PMID- 23124508
TI  - Palmitate-derivatized human IL-2: a potential anticancer immunotherapeutic of low
      systemic toxicity.
AB  - PURPOSE AND EXPERIMENTAL DESIGN: Recombinant human IL-2 (rhIL-2) is a potent
      cytokine and FDA-approved anticancer drug. However, its clinical use has been
      limited by severe toxicity, associated primarily with systemic administration
      with excess protein distributing freely throughout the body. We hypothesized that
      rhIL-2 in alternate forms permitting more restricted localization may exert
      stronger antitumor efficacy and less toxicity. Here, we have tested the utility
      of palmitate-derivatized rhIL-2. rhIL-2 was reacted with N-hydroxysuccinimide
      palmitate ester. The resultant lipidated rhIL-2 (pIL-2), when mixed with cells,
      could spontaneously transfer from solution to cell surfaces. Next, anticancer
      efficacy of pIL-2 was assessed in two modalities. For adoptive T cell therapy,
      antitumor cytotoxic T cells (CTLs) were protein transferred ("painted") with pIL
      2 and injected into mice bearing lymphoma. For in situ therapy, pIL-2 was
      injected intratumorally into mice bearing melanoma. Tumor growth and IL-2
      associated toxicity were determined. RESULTS: In the lymphoma model, painting of
      the antitumor CTLs with pIL-2 markedly increased their viability and titer. In
      the melanoma model, intratumoral injection of pIL-2, but not rhIL-2, increased
      the number of activated CD8(+) T cells (IFN-gamma(+)) in the spleen, reduced lung
      metastasis and prolonged the survival of treated mice. Moreover, while repeated
      intratumoral injection of rhIL-2 at an excessively high dose (10 injections of
      10,000 IU/mouse) caused marked vascular leakage syndrome, the same regimen using
      pIL-2 caused no detectable toxicity. CONCLUSIONS: Transferring spontaneously from
      solution to cell surfaces, pIL-2 may bypass the current limitations of rhIL-2
      and, thus, serve as a more effective and tolerable anticancer drug.

PMID- 23124509
TI  - Alzheimer's disease: an update of the roles of receptors, astrocytes and primary
      cilia (review).
AB  - The pathophysiological mechanisms underlying the onset and inexorable progression
      of the late-onset form of Alzheimer's disease (AD) are still the object of
      controversy. This review takes stock of some most recent advancements of this
      field concerning the complex roles played by the amyloid-beta (Abeta)-binding p75
      neurotrophin receptor (p75NTR) and calcium-sensing receptor (CaSR) and by the
      primary cilia in AD. Apart from their physiological roles, p75NTR is more
      intensely expressed in the hippocampus of human AD brains and Abeta-bound p75NTR
      triggers cell death, whereas Abeta-bound CaSR signalling induces the de novo
      synthesis and release of nitric oxide (NO), vascular endothelial growth factor
      (VEGF)-A and Abeta peptides (Abetas), particularly on the part of normal adult
      human astrocytes. The latter effect could significantly increase the pool of
      Abeta- and NO-producing nerve cells favouring the progressive spread of a self
      sustaining and self-reinforcing 'infectious' mechanism of neural and vascular
      (i.e. blood-brain barrier) cell damage. Interestingly, primary cilia concentrate
      p75NTR receptors in their membranes and are abnormally structured/damaged in
      transgenic (Tg) AD-model mice, which could impact on the adult neurogenesis
      occurring in the dentate gyrus's subgranular zone (SGZ) that is necessary for new
      memory encoding, thereby favouring typical AD cognitive decline. Altogether,
      these findings may pave the way to novel therapeutic approaches to AD,
      particularly in its mild cognitive impairment (MCI) and pre-MCI stages of
      development.

PMID- 23124510
TI  - Anomalous temperature dependence of magnetic anisotropy in gradient-composition
      sputterred thin films.
AB  - An abnormal behavior of increasing magnetic anisotropy with temperature in
      magnetic thin films fabricated by a gradient-composition sputtering technique is
      observed and consistently confirmed by two independent measurements of static
      magnetic hysteresis loops and dynamic magnetic permeability spectra. This
      peculiar behavior is suggested to be due to the physical origin of stress-induced
      magnetic anisotropy.

PMID- 23124511
TI  - Home haemodialysis.
AB  - Haemodialysis (HD) began as an intensive care treatment offered to a very select
      number of patients in an attempt to keep them alive. Outcomes were extremely
      poor, and the procedure was cumbersome and labor intensive. With increasing
      expertise and advances in dialysis equipment, HD is now recognised as a life
      sustaining treatment that is considered a standard of care for children with end
      stage renal disease (ESRD). Assessment of efficacy has evolved from mere
      survival, through achieving minimal standards of "adequate" dialysis with reduced
      morbidity, towards the provision of "optimal dialysis", which includes attempts
      to more closely mimic normal renal function, and of individualised care that
      maximizes the patient's health, psychosocial well-being and life potential. There
      is a renewed interest in dialysis, and the research profile has extended,
      exploring themes around convective versus diffusive treatments, HD time versus
      frequency and home versus in-centre dialysis. The results thus far have led
      dialysis care full circle from prolonged, home-based therapies to shorter,
      intense in-centre dialysis back to the belief that long or frequent HD at home
      achieves the best outcomes.

PMID- 23124514
TI  - Interleukin-17A stimulates granulocyte-macrophage colony-stimulating factor
      release by murine osteoblasts in the presence of 1,25-dihydroxyvitamin D(3)  and
      inhibits murine osteoclast development in vitro.
AB  - OBJECTIVE: To investigate the effects of interleukin-17A (IL-17A) on
      osteoclastogenesis in vitro. METHODS: Bone marrow cells (BMCs) were isolated from
      the excised tibia and femora of wild-type C57BL/6J mice, and osteoblasts were
      obtained by sequential digestion of the calvariae of ddY, C57BL/6J, and
      granulocyte-macrophage colony-stimulating factor-knockout (GM-CSF(-/-)) mice.
      Monocultures of BMCs or cocultures of BMCs and osteoblasts were supplemented with
      or without 1,25-dihydroxyvitamin D(3)(1,25[OH](2)D(3)), recombinant human
      macrophage colony-stimulating factor (M-CSF), RANKL, and IL-17A. After 5-6 days,
      the cultures were fixed with 4% paraformaldehyde and subsequently stained for the
      osteoclast marker enzyme tartrate-resistant acid phosphatase (TRAP).
      Osteoprotegerin (OPG) and GM-CSF expression were measured by enzyme-linked
      immunosorbent assay, and transcripts for RANK and RANKL were detected by real
      time polymerase chain reaction. RESULTS: In both culture systems, IL-17A alone
      did not affect the development of osteoclasts. However, the addition of IL-17A
      plus 1,25(OH)(2)D(3) to cocultures inhibited early osteoclast development within
      the first 3 days of culture and induced release of GM-CSF into the culture
      supernatants. Furthermore, in cocultures of GM-CSF(-/-) mouse osteoblasts and
      wild-type mouse BMCs, IL-17A did not affect osteoclast development, corroborating
      the role of GM-CSF as the mediator of the observed inhibition of
      osteoclastogenesis by IL-17A. CONCLUSION: These findings suggest that IL-17A
      interferes with the differentiation of osteoclast precursors by inducing the
      release of GM-CSF from osteoblasts.

PMID- 23124515
TI  - Modulation of the shape and speed of a chemical wave in an unstirred Belousov
      Zhabotinsky reaction by a rotating magnet.
AB  - The objective of this study was to observe whether a rotating magnetic field
      (RMF) could change the anomalous chemical wave propagation induced by a moderate
      intensity gradient static magnetic field (SMF) in an unstirred Belousov
      Zhabotinsky (BZ) reaction. The application of the SMF (maximum magnetic flux
      density = 0.22 T, maximum magnetic flux density gradient = 25.5 T/m, and peak
      magnetic force product (flux density * gradient) = 4 T(2) /m) accelerated the
      propagation velocity in a two-dimensional pattern. Characteristic anomalous
      patterns of the wavefront shape were generated and the patterns were dependent on
      the SMF distribution. The deformation and increase in the propagation velocity
      were diminished by the application of an RMF at a rotation rate of 1 rpm for a
      few minutes. Numerical simulation by means of the time-averaged value of the
      magnetic flux density gradient or the MF gradient force over one rotation
      partially supported the experimental observations. These considerations suggest
      that RMF exposure modulates the chemical wave propagation and that the degree of
      modulation could be, at least in part, dependent on the time-averaged MF
      distribution over one rotation. Bioelectromagnetics 34:220-230, 2013. (c) 2012
      Wiley Periodicals, Inc.

PMID- 23124512
TI  - Proteinuria and progression of glomerular diseases.
AB  - One of the major challenges of nephrology is to develop therapeutic strategies to
      halt the progression of kidney diseases. In clinical settings, nephrotic-range
      proteinuria correlates with the rate of progression, particularly in glomerular
      diseases. Hence, the degree of proteinuria has been utilized to monitor the
      response to treatment as well as to predict outcome. However, the pathophysiology
      of proteinuria-induced progression remains unknown. Albumin accounts for the
      majority of the protein in nephrotic urine and as a result of this clinical
      observation studies have focused on understanding the adverse effects of albumin
      overload in the kidney. Albumin is internalized by receptor-mediated endocytosis
      in proximal tubule cells via low density lipoprotein (LDL) type receptor,
      megalin. Albumin at high concentrations mimicking nephrotic milieu has resulted
      in the upregulation of pro-inflammatory/fibrogenic genes and apoptosis in
      proximal tubule cells in in vivo and in vitro models of albumin overload. These
      properties of albumin on proximal tubule cells may explain extensive
      tubulointerstitial fibrosis and tubular atrophy observed in end-stage kidney
      disease. In addition to tubular toxicity, podocytes respond to proteinuric states
      by cytoskeletal alterations and loss of the differentiation marker synaptopodin.
      Identifying the molecular network of proteins involved in albumin handling will
      enable us to manipulate the specific signaling pathways and prevent damage caused
      by proteinuria.

PMID- 23124516
TI  - The utilization of carotid artery imaging beyond metabolic scores and high
      sensitivity CRP in screening intermediate-to-high Framingham risk of asymptomatic
      Taiwanese population.
AB  - To compare the diagnostic accuracy of various cardiovascular screening tools in
      asymptomatic subjects with intermediate-to-high risk Framingham risk score (FRS).
      In addition, we also investigated whether carotid artery study could further add
      incremental value beyond metabolic abnormality and inflammatory marker in this
      issue. 1,200 asymptomatic subjects who underwent health evaluation were recruited
      in our study. FRS was calculated in all participants based on clinical variables,
      body surface electrocardiography, medical histories, and life styles. Metabolic
      scores, serum high-sensitivity C reactive protein (hs-CRP) level and carotid
      artery study in assessing intima-media-thickness (CIMT) and plaque were all
      obtained and compared to FRS. Comparison of diagnostic accuracy was then
      conducted among these different tools aiming at a more efficient screen in
      identifying intermediate-to-high FRS. Of all, 1,101 participants (mean age 50.6
      +/- 10.4, 38.6 % women) were finally entered in our study after exclusion of
      known cardiovascular diseases. By utilizing common carotid IMT (CCIMT) equal or
      larger than 1 mm, best specificity (98.27, 95 % CI 97.24-98.99) was achieved in
      identifying intermediate-to-high FRS subject. The most optimal cut-off in
      identifying intermediate-to-high FRS for metabolic scores, hs-CRP and CCIMT was
      2, 0.101 mg/dL and 0.65 mm, respectively. Both receiver operating characteristic
      curve and likelihood ratio tests showed that information provided by carotid
      artery study further showed significant incremental value when superimposed on
      metabolic scores and hs-CRP (all p < 0.05) in screening intermediate-to-high FRS
      subjects. Though diagnostic accuracy may differ to some degree by using different
      cut-off values, a low metabolic score seemed to have the best sensitivity with
      abnormal CCIMT yielded highest specificity in screening a subject with future
      cardiovascular risks. Carotid artery study added significant clinical incremental
      value in discriminating projected risk beyond metabolic scores and hs-CRP.

PMID- 23124517
TI  - Atypical parkinsonism and cerebrotendinous xanthomatosis: report of a family with
      corticobasal syndrome and a literature review.
AB  - Cerebrotendinous xanthomatosis is an autosomal recessive inborn error of
      cholesterol metabolism. It presents with systemic and neurological symptoms,
      rarely including parkinsonism. Presented here are a clinical description of a new
      family with cerebrotendinous xanthomatosis and parkinsonism and a review of 13
      additional cases reported in the literature. The index case developed
      corticobasal syndrome, previously not reported in cerebrotendinous xanthomatosis.
      His brother had parkinsonism with cerebellar features and cognitive impairment.
      In a literature review, median age of onset of parkinsonism was found to be 40
      years. Nearly all patients had other neurological symptoms: cognitive (93%),
      pyramidal (93%), or cerebellar (53%). All patients had walking difficulties, with
      falls in 27%. Systemic features were common: cataracts (93%) or tendon xanthomata
      (87%). Frequent MRI abnormalities included cerebellar atrophy (100%), cerebral
      atrophy (80%), and dentate nuclei signal changes (80%). Functional dopaminergic
      imaging often demonstrated presynaptic denervation. Improvement with levodopa was
      frequent (91%) but mild. Progressive neurological decline occurred in 92% of
      patients despite treatment with chenodeoxycholic acid. Cerebrotendinous
      xanthomatosis should be considered in the differential diagnosis of atypical
      parkinsonism, including corticobasal syndrome, particularly with early age of
      onset and in the context of a complex neurological phenotype. Tendon xanthomata,
      early-onset cataracts, and radiological findings of cerebellar atrophy with
      lesions of the dentate nuclei are useful clinical clues. Symptomatic treatment
      with levodopa may help, but progressive neurological decline is frequent despite
      treatment with chenodeoxycholic acid.

PMID- 23124518
TI  - Etoposide sensitizes neuroblastoma cells expressing caspase 8 to TRAIL.
AB  - TRAIL [TNF (tumour necrosis factor)-related apoptosis-inducing ligand] is a
      promising agent for clinical use since it kills a wide range of tumour cells
      without affecting normal cells. We provide evidence that pretreatment with
      etoposide significantly enhanced TRAIL-mediated apoptosis via up-regulation of
      DR5 (death receptor 5 or TRAIL-R2) expression in the caspase 8 expressing
      neuroblastoma cell line, SK-N-MC. In addition, sequential treatment with
      etoposide and TRAIL increased caspases 8, 9 and 3 activation, Mcl-1 cleavage and
      Bid truncation, which suggests that the ability of etoposide and TRAIL to induce
      apoptosis is mediated through activation of an intrinsic signalling pathway.
      Although TRAIL-R2 expression increased in IMR-32 cells in response to etoposide
      treatment, cell death was not increased by concurrent treatment with TRAIL
      compared with etoposide alone, because the cells lacked caspase 8 expression.
      Restoration of caspase 8 expression by exposure to IFNgamma (interferon gamma)
      sensitizes IMR-32 cells to TRAIL. Moreover, pretreatment with etoposide increased
      TRAIL-induced apoptosis in caspase 8 restored IMR-32 cells through activation of
      a caspase cascade that included caspases 8, 9 and 3. These results indicate that
      the etoposide-mediated sensitization of neuroblastoma cells to TRAIL is
      associated with an increase in TRAIL-R2 expression and requires caspase 8
      expression. These observations support the potential use of a combination of
      etoposide and TRAIL in future clinical trials.

PMID- 23124519
TI  - Acute toxicity bioassay with the amphipod, Grandidierella bonnieroides S. after
      exposure to sediments from an urban estuary (Macae River Estuary, RJ, Brazil).
AB  - Acute toxicity to Grandidierella bonnieroides and physicochemical analysis were
      used for quality assessment of the sediment of the Macae River urban estuary,
      located in the Brazilian coast where rapid socioeconomic growth has been induced
      by offshore oil and gas exploration at the Campos Basin. Sediment samples were
      collected during four events in four sampling sites of the estuary and also in a
      control site. Organism mortality after exposure to the estuarine sediments was,
      on average, 30 % a value higher than in the control site where it was 10 %. This
      result together with the physicochemical analysis suggests an initial toxicity
      condition of the sediments from this aquatic coastal environment.

PMID- 23124520
TI  - Somatic rearrangements across cancer reveal classes of samples with distinct
      patterns of DNA breakage and rearrangement-induced hypermutability.
AB  - Whole-genome sequencing using massively parallel sequencing technologies enables
      accurate detection of somatic rearrangements in cancer. Pinpointing large numbers
      of rearrangement breakpoints to base-pair resolution allows analysis of
      rearrangement microhomology and genomic location for every sample. Here we
      analyze 95 tumor genome sequences from breast, head and neck, colorectal, and
      prostate carcinomas, and from melanoma, multiple myeloma, and chronic lymphocytic
      leukemia. We discover three genomic factors that are significantly correlated
      with the distribution of rearrangements: replication time, transcription rate,
      and GC content. The correlation is complex, and different patterns are observed
      between tumor types, within tumor types, and even between different types of
      rearrangements. Mutations in the APC gene correlate with and, hence, potentially
      contribute to DNA breakage in late-replicating, low %GC, untranscribed regions of
      the genome. We show that somatic rearrangements display less microhomology than
      germline rearrangements, and that breakpoint loci are correlated with local
      hypermutability with a particular enrichment for   transversions.

PMID- 23124521
TI  - Constitutive nuclear lamina-genome interactions are highly conserved and
      associated with A/T-rich sequence.
AB  - In metazoans, the nuclear lamina is thought to play an important role in the
      spatial organization of interphase chromosomes, by providing anchoring sites for
      large genomic segments named lamina-associated domains (LADs). Some of these LADs
      are cell-type specific, while many others appear constitutively associated with
      the lamina. Constitutive LADs (cLADs) may contribute to a basal chromosome
      architecture. By comparison of mouse and human lamina interaction maps, we find
      that the sizes and genomic positions of cLADs are strongly conserved. Moreover,
      cLADs are depleted of synteny breakpoints, pointing to evolutionary selective
      pressure to keep cLADs intact. Paradoxically, the overall sequence conservation
      is low for cLADs. Instead, cLADs are universally characterized by long stretches
      of DNA of high A/T content. Cell-type specific LADs also tend to adhere to this
      "A/T rule" in embryonic stem cells, but not in differentiated cells. This
      suggests that the A/T rule represents a default positioning mechanism that is
      locally overruled during lineage commitment. Analysis of paralogs suggests that
      during evolution changes in A/T content have driven the relocation of genes to
      and from the nuclear lamina, in tight association with changes in expression
      level. Taken together, these results reveal that the spatial organization of
      mammalian genomes is highly conserved and tightly linked to local nucleotide
      composition.

PMID- 23124523
TI  - Value of 11C-choline PET/CT for lung cancer diagnosis and the relation between
      choline metabolism and proliferation of cancer cells.
AB  - The aim of this study was to investigate the efficacy of 11C-choline PET/CT
      imaging for lung cancer and the correlation between choline uptake of lung cancer
      tissue and the expression of choline kinase (ChoK), phosphorylcholine-cytidyl
      transferase and Ki-67 index. Between March 2008 and June 2010, 53 patients
      diagnosed or suspected of having lung cancer underwent integrated 11C-choline
      PET/CT and contrast-enhanced CT scans before surgery. After surgery, specimens
      from 42 patients diagnosed with lung cancer were used to detect the expression of
      ChoK, phosphorylcholine-cytidyl transferase and the Ki-67 index. The PET/CT
      results were analyzed using visual methods and the standardized uptake value
      (SUV) of lesions was measured using semi-quantitative methods. Finally, the
      analyzed results were compared to the histopathological results. The accuracy of
      the 11C-choline PET/CT for diagnosing lung cancer was 81.13% (43/53), compared
      with 71.70% (38/53) for CT scanning. The difference was not statistically
      significant (P=0.61). The accuracy of 11C-choline PET/CT for diagnosing lymph
      nodes was 83.76% (227/271), compared with 66.79% (181/271) for CT scanning. This
      difference was statistically significant (P=0.04); the SUVmean value of lesions
      correlated positively with the Ki-67 index (r=0.51, p=0.002). Of the 35 patients
      with positive 11C-choline PET results, 29 (82.86%) overexpressed ChoK, 26
      (74.29%) overexpressed phosphorylcholine-cytidyl transferase. The seven patients
      with negative 11C-choline PET results did not exhibit overexpression of ChoK or
      phosphorylcholine-cytidyl transferase; the SUVmean value correlated positively
      with the expression of both ChoK and phosphorylcholine-cytidyl transferase
      (r=0.52, p=0.001; r=0.37, p=0.029). In conclusion, compared with contrast
      enhanced CT, 11C-choline PET offers nodal staging with higher accuracy. The SUV
      value of PET is correlated with the proliferation of tumor cells and the
      mechanism of PET imaging is associated with the overexpression of ChoK and
      phosphorylcholine-cytidyl transferase.

PMID- 23124524
TI  - Polymer characterization and optimization of conditions for the enhanced
      bioproduction of benzaldehyde by Pichia pastoris in a two-phase partitioning
      bioreactor.
AB  - Benzaldehyde, with its apricot and almond-like aroma, is the second most
      abundantly used molecule in the flavor industry, and is most commonly produced
      via chemical routes, such as by the oxidation of toluene. Biologically produced
      benzaldehyde, whether by extraction of plant material or via microbial
      biotransformation, commands a substantial price advantage, and greater consumer
      acceptance. Methylotrophic yeast, such as Pichia pastoris, contain the enzyme
      alcohol oxidase (AOX), which, in the presence of alcohols other than methanol,
      are able to yield aldehydes as dead-end products, for example, benzaldehyde from
      benzyl alcohol. In this work, we have determined that benzaldehyde, and not
      benzyl alcohol, is inhibitory to the transformation reaction by P. pastoris,
      prompting the development of a selection strategy for identifying sequestering
      polymers for use in a partitioning bioreactor that was based on the ratio of
      partition coefficients (PCs) for the two target molecules. Additionally, we have
      now confirmed for the first time, that the mechanism of solute uptake by
      amorphous polymers is via absorption, not adsorption. Finally, we have adopted a
      common strategy used for the production of heterologous proteins by P. pastoris,
      namely the use of a mixed methanol/glycerol feed for inducing the required AOX
      enzyme, while reducing the time required for high density biomass generation. All
      of these components were combined in a final experiment in which 10% of the
      polymer Kraton D1102K, whose PC ratio of benzaldehyde to benzyl alcohol was 14.9,
      was used to detoxify the biotransformation in a 5 L partitioning bioreactor,
      resulting in a 3.4-fold increase in benzaldehyde produced (14.4 g vs. 4.2 g)
      relative to single phase operation, at more than double the volumetric
      productivity (97 mg L(-1) h(-1) vs. 41 mg L(-1) h(-1) ).

PMID- 23124522
TI  - Stabilization of the promoter nucleosomes in nucleosome-free regions by the yeast
      Cyc8-Tup1 corepressor.
AB  - The yeast Cyc8 (also known as Ssn6)-Tup1 complex regulates gene expression
      through a variety of mechanisms, including positioning of nucleosomes over
      promoters of some target genes to limit accessibility to the transcription
      machinery. To further define the functions of Cyc8-Tup1 in gene regulation and
      chromatin remodeling, we performed genome-wide profiling of changes in nucleosome
      organization and gene expression that occur upon loss of CYC8 or TUP1 and
      observed extensive nucleosome alterations in both promoters and gene bodies of
      derepressed genes. Our improved nucleosome profiling and analysis approaches
      revealed low-occupancy promoter nucleosomes (P nucleosomes) at locations
      previously defined as nucleosome-free regions. In the absence of CYC8 or TUP1,
      this P nucleosome is frequently lost, whereas nucleosomes are gained at -1 and +1
      positions, accompanying up-regulation of downstream genes. Our analysis of public
      ChIP-seq data revealed that Cyc8 and Tup1 preferentially bind TATA-containing
      promoters, which are also enriched in genes derepressed upon loss of CYC8 or
      TUP1. These results suggest that stabilization of the P nucleosome on TATA
      containing promoters may be a central feature of the repressive chromatin
      architecture created by the Cyc8-Tup1 corepressor, and that releasing the P
      nucleosome contributes to gene activation.

PMID- 23124525
TI  - A novel PET scanner with semiconductor detectors may improve diagnostic accuracy
      in the metastatic survey of head and neck cancer patients.
AB  - OBJECTIVES: Our research group developed new PET scanner with semiconductor
      detectors for high spatial resolution with low scatter noise. On head and neck
      cancer (HNC) surgery, FDG-PET may often provide false-positive findings in
      cervical node involvements. Accordingly, we assessed diagnostic accuracy using
      this new scanner in the HNC patients as compared with the conventional lutetium
      oxyorthosilicate (LSO) PET. METHODS: We prospectively studied FDG imaging in 35
      HNC patients by both semiconductor PET and LSO-PET. At 60 min after (18)F-FDG
      injection, two PET scans were obtained using both scanners consecutively and in
      random order. Two nuclear medicine specialists scored FDG abnormalities using 5
      point scale system for receiver operating characteristic (ROC) curve analysis.
      RESULTS: 63 suspected of metastatic or recurrent lesions were evaluated and
      correlated by the final confirmation by pathological findings or clinical courses
      (malignant 26/benign 37). Semiconductor PET showed sensitivity of 92.3 % (24/26),
      specificity of 51.4 % (19/37), and accuracy of 68.2 % (43/63), while LSO-PET
      showed sensitivity of 84.6 % (22/26), specificity of 16.2 %(6/37), and accuracy
      of 44.4 % (28/63), respectively. Especially, semiconductor PET accurately
      diagnosed as true negative in the 13 of 14 lesions only detected by LSO-PET. ROC
      analyses revealed the diagnostic superiority of semiconductor PET from location
      of- and area under curve particularly in the study of small (<=10 mm) lesions.
      CONCLUSION: A new novel semiconductor PET scanner can increase diagnostic
      accuracy with reduction in false positive findings in the HNC patients mainly due
      to higher spatial resolution and lower noise than the LSO-PET. This new
      technology can lead to more accurate diagnosis and the more optimal therapeutic
      tactics in head and neck surgery.

PMID- 23124526
TI  - Conducting cryogel scaffold as a potential biomaterial for cell stimulation and
      proliferation.
AB  - The aim of the study was to demonstrate the potential of the cryogelation
      technique for the synthesis of the conducting cryogel scaffolds which would
      encompass the advantages of the cryogel matrix, like the mechanical strength and
      interconnected porous network as well as the conductive properties of the
      incorporated conducting polymeric material, polypyrrole. The cryogels were
      synthesized using different combinations of oxidizing agents and surfactants
      like, sodium dodecyl sulfate (SDS)/ammonium persulfate (APS), SDS/iron chloride
      (FeCl(3)), cetyl trimethyl ammonium bromide (CTAB)/APS, and CTAB/FeCl(3). The
      synthesized gels were characterized by scanning electron microscopic analysis for
      morphology, Fourier transform infrared spectroscopy for analyzing the presence of
      the polypyrrole (0.5-4 %) as nano-fillers in the gel. It was observed that the
      presence of these nano-fillers increased the swelling ratio by approximately 50
      %. The synthesized conducting cryogels displayed high stress bearing capacity
      without being deformed as analysed by rheological measurements. The degradation
      studies showed 12-15 % degradation in 4 weeks time. In vitro studies with
      conducting and non-conducting cryogel scaffold were carried out to optimize the
      stimulation conditions for the two cell lines, neuro2a and cardiac muscle C2C12.
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed
      approximately 25 and 15 % increase in the cell proliferation rate for neuro2a and
      C2C12 cell line, respectively. This was observed at a specific voltage of 100 mV
      and 2 V, for a specified duration of 2 h and 1 min, respectively for the
      conducting scaffold as compared to the control. This can play an important role
      in tissue engineering applications for cell lines where acquiring a high cell
      number and functionality is desired.

PMID- 23124527
TI  - Plasma surface modification of polylactic acid to promote interaction with
      fibroblasts.
AB  - In this work, medium pressure plasma treatment of polylactic acid (PLA) is
      investigated. PLA is a biocompatible aliphatic polymer, which can be used for
      bone fixation devices and tissue engineering scaffolds. Due to inadequate surface
      properties, cell adhesion and proliferation are far less than optimal and a
      surface modification is required for most biomedical applications. By using a
      dielectric barrier discharge (DBD) operating at medium pressure in different
      atmospheres, the surface properties of a PLA foil are modified. After plasma
      treatment, water contact angle measurements showed an increased hydrophilic
      character of the foil surface. X-ray photoelectron spectroscopy (XPS) revealed an
      increased oxygen content. Cell culture tests showed that plasma modification of
      PLA films increased the initial cell attachment both quantitatively and
      qualitatively. After 1 day, cells on plasma-treated PLA showed a superior cell
      morphology in comparison with unmodified PLA samples. However, after 7 days of
      culture, no significant differences were observed between untreated and plasma
      modified PLA samples. While plasma treatment improves the initial cell
      attachment, it does not seem to influence cell proliferation. It has also been
      observed that the difference between the 3 discharge gases is negligible when
      looking at the improved cell-material interactions. From economical point of
      view, plasma treatments in air are thus the best choice.

PMID- 23124528
TI  - Functional results and quality of life after bilateral scaphoid reconstruction: a
      case series.
AB  - Unilateral scaphoid non-union remains a major problem, which can lead to major
      functional limitations. Until now there is no evidence of outcome of the rare
      case of bilateral scaphoid non-unions and in how far two-stage bilateral
      reconstruction affects functional results and the quality of life. Between 1997
      and 2010, altogether four bilateral scaphoid non-unions were treated in the
      centre and retrospectively analyzed. The mean follow-up was performed 36.8 months
      after reconstruction. The measures included analysis of patient data, analysis of
      functional measures and quality of life after follow-up. The reconstructions were
      performed with implantation of a free, non-vascularized iliac crest bone graft
      (4), osteosynthesis with implantation of a pedicled vascularized bone graft (3)
      and osteosynthesis with cancellous bone graft (1). The mean range of motion of
      the wrist was extension/flexion 111.3 degrees . The average grip strength by
      JAMAR dynamometer showed right versus left sight 32.7 kg (+/-3.5) versus 33.7 (+/
      2.9). The evaluation of the DASH score resulted in 11.6 (+/-12.5), the SF36 scale
      in 87.1 (+/-9.2) points. The present case series for the first time demonstrated
      functional mid-term results of the rare event of bilateral scaphoid
      reconstruction after non-union. With respect to the impact on one affected hand,
      functional results, DASH score and quality of life are excellent and thus justify
      good prognosis in patient education after injury.

PMID- 23124529
TI  - The relation between mindfulness and fear of negative evaluation over the course
      of cognitive behavioral therapy for social anxiety disorder.
AB  - OBJECTIVES: This study examined the relation between mindfulness and fear of
      negative evaluation over the course of nonmindfulness based cognitive-behavioral
      therapy (CBT) for social anxiety disorder (SAD). We expected that higher levels
      of mindfulness would be associated with a more positive response to treatment.
      METHOD: This study is a secondary report from a randomized controlled trial in
      which participants (N = 65) diagnosed with SAD were randomly assigned to receive
      8 weeks of 1 of 2 manualized treatments (exposure group therapy, n = 33; or
      virtual reality exposure therapy, n = 32) either immediately or following an 8
      week waiting period. RESULTS: Fear of negative evaluation decreased following
      treatment and was negatively related to mindfulness throughout treatment and
      follow-up. Mindfulness did not moderate treatment outcome. CONCLUSIONS: These
      findings indicate that while mindfulness is related to fear, it is not a
      moderator of symptom reduction in nonmindfulness-based treatment. Implications
      for treatment and future research are discussed.

PMID- 23124530
TI  - Multivalent design of apoptosis-inducing bid-BH3 peptide-oligosaccharides boosts
      the intracellular activity at identical overall peptide concentrations.
AB  - Multivalent peptide-oligosaccharide conjugates were prepared and used to
      investigate the multivalency effect concerning the activity of Bid-BH3 peptides
      in live cells. Dextran oligosaccharides were carboxyethylated selectively in the
      2-position of the carbohydrate units and activated for the ligation of N
      terminally cysteinylated peptides. Ligation through maleimide coupling was found
      to be superior to the native chemical ligation protocol. Monomeric Bid-BH3
      peptides were virtually inactive, whereas pentameric peptide conjugates induced
      apoptosis up to 20-fold stronger at identical peptide concentrations. Comparison
      of lowly multivalent and highly multivalent peptide dextrans proved a
      multivalency effect in life cells which was specific for the BH3 peptide
      sequence.

PMID- 23124531
TI  - Ground reaction forces and center of mass mechanics of bipedal capuchin monkeys:
      implications for the evolution of human bipedalism.
AB  - Tufted capuchin monkeys are known to use both quadrupedalism and bipedalism in
      their natural environments. Although previous studies have investigated limb
      kinematics and metabolic costs, their ground reaction forces (GRFs) and center of
      mass (CoM) mechanics during two and four-legged locomotion are unknown. Here, we
      determine the hind limb GRFs and CoM energy, work, and power during bipedalism
      and quadrupedalism over a range of speeds and gaits to investigate the effect of
      differential limb number on locomotor performance. Our results indicate that
      capuchin monkeys use a "grounded run" during bipedalism (0.83-1.43 ms(-1)) and
      primarily ambling and galloping gaits during quadrupedalism (0.91-6.0 ms(-1)).
      CoM energy recoveries are quite low during bipedalism (2-17%), and in general
      higher during quadrupedalism (4-72%). Consistent with this, hind limb vertical
      GRFs as well as CoM work, power, and collisional losses are higher in bipedalism
      than quadrupedalism. The positive CoM work is 2.04 +/- 0.40 Jkg(-1) m(-1)
      (bipedalism) and 0.70 +/- 0.29 Jkg(-1) m(-1) (quadrupedalism), which is within
      the range of published values for two and four-legged terrestrial animals. The
      results of this study confirm that facultative bipedalism in capuchins and other
      nonhuman primates need not be restricted to a pendulum-like walking gait, but
      rather can include running, albeit without an aerial phase. Based on these
      results and similar studies of other facultative bipeds, we suggest that
      important transitions in the evolution of hominin locomotor performance were the
      emergences of an obligate, pendulum-like walking gait and a bouncy running gait
      that included a whole-body aerial phase.

PMID- 23124534
TI  - Infrared spectra, Raman spectra, microwave dielectric properties and simulation
      for effective permittivity of temperature stable ceramics AMoO4-TiO2 (A = Ca,
      Sr).
AB  - In this work, temperature stable microwave dielectric materials (1 - x)AMoO(4)
      xTiO(2) (A = Ca, Sr) were prepared by a solid state reaction method. The phase
      composition, sintering behaviors, microstructures, microwave dielectric
      properties, effective permittivity and vibrational phonon modes were
      investigated. The X-ray diffraction pattern and scanning electron microscope
      analysis indicated that the AMoO(4) (A = Ca, Sr) phase could coexist with the
      TiO(2) phase. The effective dielectric constants of the AMoO(4)-TiO(2) composites
      were calculated by the finite element method (FEM), compared with the measured
      values and the numerical results obtained by the classical mixing rules. The
      correlation between the dielectric properties and the crystal structures were
      studied using IR and Raman spectroscopy. The infrared spectra were analyzed using
      the classical harmonic oscillator model, and revealed that the external vibration
      modes of AMoO(4) (A = Ca, Sr) had the most significant influence on the
      dielectric constant. The Raman spectra showed that there were strong interactions
      in the [MoO(4)] tetrahedron due to the sharp and intense Raman modes. Finally,
      the low-firing (900  degrees C) microwave dielectric ceramics were obtained with
      3 wt% H(3)BO(3)-CuO addition (BCu), and they possess good microwave dielectric
      properties with epsilon(r) = 10.6-13, high Q*f values (40 700-72 050 GHz), and
      near-zero temperature coefficients of resonant frequency (TCF or tau(f) values).
      These results also show that (1 - x)AMoO(4)-xTiO(2)-BCu (A = Ca, Sr) ceramics are
      good candidates for microwave electronic device applications.

PMID- 23124532
TI  - The independent effect of body mass index on health-related quality of life among
      racial and ethnic subgroups.
AB  - PURPOSE: To evaluate the impact of race/ethnicity on the relationship between
      body mass index (BMI) and health-related quality of life (HRQOL) among blacks,
      Hispanics, and whites. METHODS: We used the Sinai Urban Health Institute's
      Improving Community Health Survey dataset to measure physical and mental HRQOL
      using the Physical Component Score (PCS-12) and the Mental Component Score (MCS
      12) of the Short Form-12. Multivariate linear regression models were applied to
      the overall sample and in models stratified by race/ethnicity to evaluate the
      effects of BMI on physical and mental HRQOL outcome variables while controlling
      for confounders. RESULTS: Considering physical HRQOL, increasing BMI was
      independently associated with worse PCS-12 (beta = -0.22, p value <0.001) in the
      overall sample; the magnitude was not significantly different across
      racial/ethnic subgroups (blacks: beta = -0.18, p value = 0.02; Hispanics: beta = 
      0.28, p value = 0.01; whites: beta = -0.20, p value = 0.02). Overall, Hispanic
      participants reported a worse PCS-12 compared to whites (beta = -3.06, p value =
      0.002). Considering mental HRQOL, BMI was not significantly associated with MCS
      12 in the overall sample (beta = -0.06, p value = 0.21) nor was BMI significantly
      associated with MCS-12 in any racial/ethnic subgroups. Overall, black
      participants reported better MCS-12 compared to whites (beta = 2.51, p value =
      0.001). CONCLUSIONS: BMI was associated with worse physical HRQOL to a similar
      degree among blacks, Hispanics, and whites. This finding suggests that
      interventions leading to obesity reduction should be associated with substantial
      and equal improvements in the physical HRQOL of all race/ethnicity groups.

PMID- 23124533
TI  - A practical definition of minor stroke.
AB  - It is generally assumed that minor stroke (MS) is an ischemic stroke with a short
      term, good functional outcome. However, no clear definition of MS exists.
      Modified Rankin Scale (mRS) and National Institute of Health Stroke Scale (NIHSS)
      are still the most accredited standards, but scores and timing of the assessment
      are not homogeneous. As suggested by a qualified sample of Italian neurologists,
      the index parameter chosen in our analysis was mRS at the time of hospital
      discharge. The database of the SIRIO study (a large observational study of 2,573
      patients with stroke admitted in Italian hospitals in 2005) was used to identify
      an mRS threshold to define MS. Reference was made to outcome markers such as rate
      of discharge to home, 1-year disability and 1-year mortality. The rate of
      discharge progressively decreased with increase in mRS, while the rates of 1-year
      mortality and disability progressively increased. Our proposal is one of defining
      a stroke "minor" when the rate of discharge to home is above the SIRIO database
      overall value and the 1-year mortality and disability is below the respective
      overall values. This definition is consistent with a score <=2 on the mRS. 

PMID- 23124536
TI  - Effects of vacuum packing on eggshell microbial activity and egg quality in table
      eggs under different storage temperatures.
AB  - BACKGROUND: The aim of this study was to establish the effects of vacuum packing
      on eggshell microbial activity and egg quality traits in table eggs during 42
      days of storage at 5 and 22  degrees C. Treatments were no vacuum packing
      (control) and vacuum packing (VP). Egg quality traits measured included egg
      weight loss, specific gravity, shell strength, albumen height, Haugh unit, yolk
      index, albumen pH, yolk pH, albumen colour and yolk colour. RESULTS: VP eggs
      maintained higher specific gravity, albumen height, Haugh unit and yolk index and
      lower egg weight loss, albumen pH and yolk pH compared with control eggs after 42
      days at 22  degrees C. VP eggs had lower levels of total aerobic mesophilic
      bacteria, Salmonella spp., Staphylococcus spp. and moulds/yeasts than control
      eggs over the storage period at both 5 and 22  degrees C. However, VP eggs had a
      higher level of coliforms than control eggs after 42 days at 5  degrees C.
      CONCLUSION: The results indicated that vacuum packing extended the egg shelf life
      to at least 42 days compared with control eggs at 5 and 22  degrees C.

PMID- 23124535
TI  - Association of fibromyalgia with altered skeletal muscle characteristics which
      may contribute to postexertional fatigue in postmenopausal women.
AB  - OBJECTIVE: To identify muscle physiologic properties that may contribute to
      postexertional fatigue and malaise in women with fibromyalgia (FM). METHODS:
      Healthy postmenopausal women with (n = 11) and without (n = 11) FM, ages 51-70
      years, participated in this study. Physical characteristics and responses to self
      reported questionnaires were evaluated. Strength loss and tissue oxygenation in
      response to a fatiguing exercise protocol were used to quantify fatigability and
      the local muscle hemodynamic profile. Muscle biopsies were performed to assess
      between-group differences in baseline muscle properties using histochemical,
      immunohistochemical, and electron microscopic analyses. RESULTS: There was no
      significant difference between healthy controls and FM patients in muscle fatigue
      in response to exercise. However, self-reported fatigue and pain were correlated
      with prolonged loss of strength following 12 minutes of recovery in patients with
      FM. Although there was no difference in percent succinate dehydrogenase (SDH)
      positive (type I) and SDH-negative (type II) fibers or in mean fiber cross
      sectional area between groups, FM patients exhibited greater variability in fiber
      size and altered fiber size distribution. In healthy controls only, fatigue
      resistance was strongly correlated with the size of SDH-positive fibers and
      hemoglobin oxygenation. In contrast, FM patients with the highest percentage of
      SDH-positive fibers recovered strength most effectively, and this was correlated
      with capillary density. However, overall, capillary density was lower in the FM
      group. CONCLUSION: Peripheral mechanisms, i.e., altered muscle fiber size
      distribution and decreased capillary density, may contribute to postexertional
      fatigue in FM. Understanding of these defects in fibromyalgic muscle may provide
      valuable insight with regard to treatment.

PMID- 23124537
TI  - Late recovery of renal function by rituximab in a patient with Wegener's
      granulomatosis.
AB  - BACKGROUND: Rituximab has proven effective in the treatment of complicated
      granulomatosis with polyangiitis (Wegener's, GPA). Two controlled trials in
      adults demonstrated beneficial effects of rituximab compared to cyclophosphamide
      in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis to induce
      remission and to treat relapses. Pediatric experience with rituximab in GPA is
      limited; the impact on renal function is unknown. CASE-DIAGNOSIS/TREATMENT: We
      report a female adolescent with GPA and necrotizing glomerulonephritis that lead
      to end-stage renal disease (ESRD). After 22 months of peritoneal dialysis, she
      still experienced relapses and major treatment-associated adverse effects. After
      a single dose of rituximab, she rapidly achieved clinical remission and,
      unexpectedly, steadily recovered glomerular filtration rate, plateauing at 25
      ml/min/1.73 m(2). Peritoneal dialysis could be discontinued for 16 months.
      CONCLUSIONS: This case documents a potent beneficial effect of rituximab on renal
      manifestation of GPA even in long-established ESRD.

PMID- 23124538
TI  - Effects of guided imagery on biobehavioral factors in women with fibromyalgia.
AB  - Women diagnosed with fibromyalgia (N = 72) participated in a 10-week randomized
      trial to examine the effectiveness of guided imagery on self-efficacy, perceived
      stress, and selected biobehavioral factors (FMS symptoms; immune biomarkers).
      Participants in both guided imagery and usual care control conditions completed
      measures and donated 3 cc of blood at baseline, 6- and 10-weeks. A mixed effects
      linear model to test for differences between groups for all behavioral and
      biologic variables demonstrated that after 10 weeks of daily intervention use,
      guided imagery participants reported statistically significant increases in self
      efficacy and statistically significant decreases in stress, fatigue, pain, and
      depression. There were no statistically significant changes in biomarker levels,
      although total group C-reactive protein was elevated at baseline (4.7 mg/L),
      indicating an inflammatory process. Subsequent studies should be undertaken to
      more fully elucidate the biobehavioral aspects of nonpharmacological intervention
      effectiveness. 

PMID- 23124546
TI  - PCDD/Fs, PBDD/Fs, and PBDEs in the air of an e-waste recycling area (Taizhou) in
      China: current levels, composition profiles, and potential cancer risks.
AB  - Atmospheric concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans
      (PCDD/Fs), polybrominated dibenzo-p-dioxins and dibenzofurans (PBDD/Fs), and
      polybrominated diphenyl ethers (PBDEs) were measured in Taizhou, a large
      electronic equipment waste (e-waste) recycling area in East China. The mean
      concentrations (in summer and winter) of PCDD/Fs (0.45 and 0.39 pg WHO-TEQ m-3,
      where WHO-TEQ is the toxic equivalent set by the World Health Organisation),
      PBDD/Fs (0.22 and 0.18 pg WHO-TEQ m-3), and PBDEs (270 and 225 pg m-3) in this
      region have declined compared with those in 2005, due to regulations on primitive
      e-waste recycling activities. However, these concentrations remain higher than
      the historically highest levels in Europe and North America. The congener
      profiles of 2,3,7,8-substituted PCDD/Fs were similar, with OCDD, 1,2,3,4,6,7,8
      HpCDF, OCDF, and 1,2,3,4,6,7,8-HpCDD being the most abundant congeners at all
      sites. The PCDD/F homologue profiles in the present study were different from
      those typically observed at non-e-waste locations, indicating a distinct source
      in this region. Seasonal differences were found in the lower brominated PBDE
      profiles. These differences indicate that the PBDE emission sources in summer
      (e.g., strong evaporation sources) differed from those in winter. However, the
      relatively steady congener profiles of the highly brominated PBDEs suggest that
      these PBDEs were controlled primarily by similar emission mechanisms. The
      lifetime excess cancer risks from exposure to PCDD/Fs and PBDD/Fs via inhalation
      ranged from 0.7 * 10-5 to 5.4 * 10-5, or approximately 80 cancer cases in the
      Taizhou population.

PMID- 23124547
TI  - Clinical significance of human leukocyte antigen loss and melanoma-associated
      antigen 4 expression in smokers of non-small cell lung cancer patients.
AB  - BACKGROUND: Melanoma-associated antigen-A4 (MAGE-A4) is one of the candidates for
      a target of immunotherapy and is expressed in non-small cell lung cancer (NSCLC).
      However, tumors sometimes lose human leukocyte antigen (HLA) class I expression,
      and tumor-specific T cells cannot eliminate the tumor with loss of HLA. However,
      the relationship between MAGE-A4 expression and HLA loss has remained unclear.
      METHODS: Among 363 NSCLC patients who consecutively underwent curative surgery,
      187 cases whose material could be analyzed were reviewed. The expression of HLA
      class I molecules was assessed by immunohistochemical staining. The expression of
      MAGE-A4 was analyzed by RT-PCR. RESULTS: Seventy-seven tumors expressed HLA
      normally; however, 110 tumors lost HLA. The proportion of patients with a smoking
      habit and expressing the MAGE-A4 gene in patients with HLA loss was higher than
      those with HLA expression (p = 0.04 and 0.028, respectively). Five-year overall
      survival (OS) rate in the patients expressing MAGE-A4 but with loss of HLA was
      52.4 %, and OS was significantly poorer than their counterparts (74.0 %, p =
      0.036). Multivariate analysis indicated that advanced stage or history of smoking
      and HLA loss was an independently poor prognostic predictor of OS in NSCLC (p <
      0.01 and p = 0.04, respectively). CONCLUSION: HLA class I loss in NSCLC was
      related to smoking history and MAGE-A4 expression of tumors. HLA class I loss in
      smokers or patients with the MAGE-A4 gene was a prognostic factors in NSCLC.

PMID- 23124548
TI  - Selected variants of the melanocortin 4 receptor gene (MC4R) do not confer
      susceptibility to female pattern hair loss.
AB  - Female pattern hair loss (FPHL) is a common hair loss disorder in women with a
      complex mode of inheritance. Its etiopathogenesis is poorly understood.
      Widespread assumptions of overlapping susceptibility variants between FPHL and
      male pattern baldness (androgenetic alopecia) and a crucial role of androgens or
      distinct sexual steroid hormones in the development of FPHL could neither be
      clearly demonstrated nor completely excluded at the molecular level up to date.
      Interestingly, recent studies suggested an association of metabolic syndrome
      including obesity, hyperlipidaemia, hypertension and diabetes mellitus type 2 or
      abnormally high fasting blood glucose-with FPHL. Of note, mutations in the
      melanocortin 4 receptor gene (MC4R) have been identified in patients with morbid
      obesity. Interestingly, this neuropeptide receptor has been detected amongst
      others in the dermal papilla of the hair follicle. As almost half of our FPHL
      patients of German origin present with adipositas and/or obesity, we hypothesized
      as to whether FPHL could be associated with variants of the MC4R gene. Thus, we
      genotyped a total of six variants from MC4R in our case-control sample comprising
      245 UK patients of German and UK origin. However, based on our present study none
      of the genotyped MC4R variants displayed any significant association, neither in
      the overall UK and German samples nor in any subgroup analyses. In summary, these
      results do not point to an involvement of MC4R in FPHL.

PMID- 23124549
TI  - Light-responsive current generation by phototrophically enriched anode biofilms
      dominated by green sulfur bacteria.
AB  - The objective of this study was to employ microbial electrochemical cells (MXCs)
      to selectively enrich and examine anoxygenic photosynthetic bacteria for
      potential anaerobic respiration capabilities using electrodes. In the process, we
      designed a novel enrichment strategy that manipulated the poised anode potential,
      light, nitrogen availability, and media supply to promote growth of phototrophic
      bacteria while minimizing co-enrichment of non-phototrophic anode-respiring
      bacteria (ARB). This approach resulted in light-responsive electricity generation
      from fresh- and saltwater inocula. Under anoxic conditions, current showed a
      negative light response, suggesting that the enriched phototrophic consortia
      shifted between phototrophic and anaerobic respiratory metabolism. Molecular,
      physical, and electrochemical analyses elucidated that anode biofilms were
      dominated by green sulfur bacteria, and biofilms exhibited anode respiration
      kinetics indicative of non-mediated electron transfer, but kinetic parameters
      differed from values previously reported for non-phototrophic ARB. These results
      invite the utilization of MXCs as microbiological tools for exploring anaerobic
      respiratory capabilities among anoxygenic photosynthetic bacteria.

PMID- 23124550
TI  - Changes in determinants of deforestation and forest degradation in Popa Mountain
      Park, Central Myanmar.
AB  - Implementing effective conservation requires an understanding of factors
      affecting deforestation and forest degradation. Previous studies have
      investigated factors affecting deforestation, while few studies have examined the
      determinants of both of deforestation and forest degradation for more than one
      period. To address this gap, this study examined factors influencing
      deforestation and forest degradation during 1989-2000 and 2000-2005 in the Popa
      Mountain Park, Myanmar. We applied multinomial logistic regression (MNL) using
      land cover maps derived from Landsat images as the dependent variables as well as
      spatial and biophysical factors as the independent variables. The MNL models
      revealed influences of the determinants on deforestation and forest degradation
      changes over time. For example, during 1989-2000, deforestation from closed
      forest was positively correlated to the distance from the park boundary and was
      negatively correlated with distance from villages, roads, the park circular road,
      slope, western aspect and elevation. On the other hand, during 2000-2005,
      deforestation of closed forest was positively correlated with distance from
      villages, roads, the park circular road, slope and western aspect, and negatively
      correlated with distance from the park boundary and elevation. Similar scenarios
      were observed for the deforestation of open forest and forest degradation of
      closed forest. The study also found most of the determinants influenced
      deforestation and forest degradation differently. The changes in determinants of
      deforestation and forest degradation over time might be attributable to the
      general decrease in resource availability and to the effect of conservation
      measures conducted by the park.

PMID- 23124551
TI  - Dam design can impede adaptive management of environmental flows: a case study
      from the Opuha Dam, New Zealand.
AB  - The Opuha Dam was designed for water storage, hydropower, and to augment summer
      low flows. Following its commissioning in 1999, algal blooms (dominated first by
      Phormidium and later Didymosphenia geminata) downstream of the dam were
      attributed to the reduced frequency and magnitude of high-flow events. In this
      study, we used a 20-year monitoring dataset to quantify changes associated with
      the dam. We also studied the effectiveness of flushing flows to remove periphyton
      from the river bed. Following the completion of the dam, daily maximum flows
      downstream have exceeded 100 m(3) s(-1) only three times; two of these floods
      exceeded the pre-dam mean annual flood of 203 m(3) s(-1) (compared to 19 times
      >100 m(3) s(-1) and 6 times >203 m(3) s(-1) in the 8 years of record before the
      dam). Other changes downstream included increases in water temperature, bed
      armoring, frequency of algal blooms, and changes to the aquatic invertebrate
      community. Seven experimental flushing flows resulted in limited periphyton
      reductions. Flood wave attenuation, bed armoring, and a shortage of surface sand
      and gravel, likely limited the effectiveness of these moderate floods. Floods
      similar to pre-dam levels may be effective for control of periphyton downstream;
      however, flushing flows of that magnitude are not possible with the existing dam
      infrastructure. These results highlight the need for dams to be planned and built
      with the capacity to provide the natural range of flows for adaptive management,
      particularly high flows.

PMID- 23124552
TI  - Grading of parameters for urban tree inventories by city officials, arborists,
      and academics using the delphi method.
AB  - Tree inventories are expensive to conduct and update, so every inventory carried
      out must be maximized. However, increasing the number of constituent parameters
      increases the cost of performing and updating the inventory, illustrating the
      need for careful parameter selection. This article reports the results of a
      systematic expert rating of tree inventories aiming to quantify the relative
      importance of each parameter. Using the Delphi method, panels comprising city
      officials, arborists, and academics rated a total of 148 parameters. The total
      mean score, the top ranking parameters, which can serve as a guide for decision
      making at practical level and for standardization of tree inventories, were:
      Scientific name of the tree species and genera, Vitality, Coordinates, Hazard
      class, and Identification number. The study also examined whether the different
      responsibilities and usage of urban tree databases among organizations and people
      engaged in urban tree inventories affected their prioritization. The results
      revealed noticeable dissimilarities in the ranking of parameters between the
      panels, underlining the need for collaboration between the research community and
      those commissioning, administrating, and conducting inventories. Only by applying
      such a transdisciplinary approach to parameter selection can urban tree
      inventories be strengthened and made more relevant.

PMID- 23124553
TI  - Improving national-scale carbon stock inventories using knowledge on land use
      history.
AB  - National-scale inventories of soil organic carbon (SOC) and forest floor carbon
      (FFC) stocks have a high uncertainty. Inventories are often based on the
      interpolation of sampled information, often using a number of covariables to help
      such interpolation. The rationale for the choice of these covariables is not
      always documented, despite the fact that many local-scale studies have identified
      the factors explaining spatial variability of SOC and FFC stocks. These studies
      indicate, among others the importance of long-term land use history. Despite
      this, information on the effects of land use history has never been used to
      explain variability of carbon stocks in national-scale inventories. We designed
      an alternative method to improve national-scale inventories of SOC and FCC for
      the Dutch sand area that takes stock of the findings of detailed case studies.
      Determinants for SOC and FFC stocks derived from landscape-scale case studies
      were used to map national-scale spatial variability and to calculate national
      totals. The resulting national-scale spatial distribution was compared with the
      SOC stock map from the current Dutch greenhouse gas inventory. Using land use
      history to explain SOC variability decreased the error of the SOC stock estimate
      in 60 % of the area. The error in FFC stocks decreased in half of the forest area
      after including soil fertility, tree species, and forest age as explanatory
      factors. Estimates with reduced uncertainty will make land use and land
      management a more attractive and acceptable mitigation option to reduce emissions
      of greenhouse gases for the LULUCF sector.

PMID- 23124555
TI  - Shared pathogeneses of posttrauma pathologies: attachment, emotion regulation,
      and cognitions.
AB  - OBJECTIVE: To demonstrate how intrapersonal functioning variables related to
      attachment, cognition, and emotion are implicated in mental health outcomes for
      two samples of interpersonal trauma survivors, including undergraduates and women
      from the community. METHOD: Two samples of survivors of interpersonal trauma were
      included: undergraduates (n = 290, 60% female) and intimate partner violence
      survivors from the community (n = 114). Participants completed self-report
      measures that assessed psychopathology, emotion dysregulation, attachment
      processes, and cognitions about the world, self, and others. RESULTS: Emotion
      dysregulation was strongly linked to symptoms of depression, posttraumatic stress
      disorder, and somatization in both samples. Cognitions also accounted for unique
      variance in predicting symptoms of depression and somatization in both samples.
      CONCLUSIONS: Results suggest that disruption in the ability to regulate emotions
      is the most consistent predictor of mental health in survivors of interpersonal
      trauma, followed by cognitions regarding the world, self, and others. Treatment
      implications are discussed.

PMID- 23124556
TI  - 4-methylumbelliferone leads to growth arrest and apoptosis in canine mammary
      tumor cells.
AB  - Hyaluronan (HA), a major component of the extracellular matrix (ECM), is
      synthesized by HA synthase (HAS) 1, HAS2 and HAS3 and is intricately involved in
      cell growth and metastasis. The HA synthesis inhibitor 4-methylumbelliferone (4
      MU) has been reported to exhibit anticancer properties in various types of
      malignant tumors. However, the underlying mechanisms at the molecular and
      cellular levels remain unclear. In this study, to establish an animal model for
      studying the function of HA in human breast cancer, we investigated the antitumor
      effects of 4-MU using canine mammary tumor (CF33) cells. First, we investigated
      the effects of 4-MU on HA production in CF33 cells. Quantitative analysis of HA
      in culture media showed that 4-MU inhibited HA synthesis, accompanied by
      downregulation of HAS2 mRNA levels, in a dose-dependent manner at 24-72 h.
      Additionally, we observed a 4-MU-mediated decrease in the extent of the cell
      associated HA matrix. We examined the effect of 4-MU on cell growth and apoptosis
      in CF33 cells. 4-MU markedly inhibited cell proliferation and induced apoptosis
      in CF33 cells. In particular, our experiments showed that the mechanism of 4-MU
      induced apoptosis in CF33 cells involved increased levels of expression of pro
      apoptotic BAX mRNA and protein molecules. These data suggest that 4-MU may be a
      candidate therapeutic agent for the treatment of canine mammary tumors.
      Furthermore, this study provides the first indication that the canine mammary
      tumor may be a suitable model for comparative study of the function of HA in
      human breast cancer.

PMID- 23124558
TI  - United3D: a protein model quality assessment program that uses two consensus
      based methods.
AB  - In protein structure prediction, such as template-based modeling and free
      modeling (ab initio modeling), the step that assesses the quality of protein
      models is very important. We have developed a model quality assessment (QA)
      program United3D that uses an optimized clustering method and a simple Calpha
      atom contact-based potential. United3D automatically estimates the quality scores
      (Qscore) of predicted protein models that are highly correlated with the actual
      quality (GDT_TS). The performance of United3D was tested in the ninth Critical
      Assessment of protein Structure Prediction (CASP9) experiment. In CASP9, United3D
      showed the lowest average loss of GDT_TS (5.3) among the QA methods participated
      in CASP9. This result indicates that the performance of United3D to identify the
      high quality models from the models predicted by CASP9 servers on 116 targets was
      best among the QA methods that were tested in CASP9. United3D also produced high
      average Pearson correlation coefficients (0.93) and acceptable Kendall rank
      correlation coefficients (0.68) between the Qscore and GDT_TS. This performance
      was competitive with the other top ranked QA methods that were tested in CASP9.
      These results indicate that United3D is a useful tool for selecting high quality
      models from many candidate model structures provided by various modeling methods.
      United3D will improve the accuracy of protein structure prediction.

PMID- 23124557
TI  - Capsofulvesins A-C, cholinesterase inhibitors from Capsosiphon fulvescens.
AB  - Activity-directed isolation of the n-hexane and dichloromethane fractions of
      Capsosiphon fulvescens resulted in the identification of four new glycolipids (1
      3): (2S)-1-O-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-O-(4Z,7Z,10Z,13Z
      hexadecatetraenoyl)-3-O-beta-D-galactopyranosyl glycerol (1, capsofulvesin A),
      (2S)-l-O-(9Z,12Z,15Z-octadecatrienoyl)-2-O-(10Z,13Z-hexadecadienoyl)-3-O-beta-D
      galactopyranosyl glycerol (2, capsofulvesin B), (2S)-1-O-(6Z,9Z,12Z,15Z
      octadecatetraenoyl)-3-O-beta-D-galacatopyranosyl glycerol (3, capsofulvesin C).
      Compounds 1-6 exhibited acetylcholinesterase (AChE) inhibitory activities with
      IC(50) values ranging from 50.90 to 82.83 uM, whereas 2-6 showed
      butyrylcholinesterase (BChE) inhibitory activities with IC(50) values of 114.75
      185.55 uM. Although most of the compounds isolated lacked scavenging activity for
      1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and peroxynitrite (ONOO(-)),
      compound 8 showed ONOO(-) scavenging activity with an IC(50) value of 26.23
      ug/mL.

PMID- 23124559
TI  - Influence of manufacturing factors on physical stability and solubility of solid
      dispersions containing a low glass transition temperature drug.
AB  - In this study, we investigated the effect of manufacturing factors such as
      particle size, water content and manufacturing method on the physical stability
      and solubility of solid dispersion formulations of a low-glass-transition
      temperature (T(g)) drug. Solid dispersions were prepared from
      polyvinylpyrrolidone (PVP) and hydroxypropylmethylcellulose (HPMC) by hot melt
      extrusion or spray drying. Water content of solid dispersions prepared by hot
      melt extrusion determined by dynamic moisture sorption measurement was increased
      drastically with relative humidity below a certain level of particle size. The
      blends with a lower water content (0.8%) prepared by hot melt extrusion during
      storage were more stable than those with a higher water content (3.5%) prepared
      by spray drying, which caused rapid recrystallization. Physical stability in the
      hot melt blends may be attributed to reduced molecular mobility due to a higher
      T(g). Dissolution study revealed that solid dispersions prepared by hot melt
      extrusion with the smallest particle size showed decreased solubility, attributed
      to reduced wetting properties (surface energy), which is not predictable by the
      Noyes-Whitney equation. Taken together, these results indicate that the control
      of particle size concerned in water content or wetting properties is critical to
      ensuring the physical stability or enhancing solubility of low-T(g) drugs.
      Further, hot melt extrusion, which can reduce water content, is a suitable
      manufacturing method for solid dispersions of low-T(g) drugs.

PMID- 23124560
TI  - Synthesis, antitumor, antitrypanosomal and antileishmanial activities of
      benzo[4,5]canthin-6-ones bearing the N'-(Substituted benzylidene)-carbohydrazide
      and N-Alkylcarboxamide groups at C-2.
AB  - A series of novel benzo[4,5]canthin-6-ones, bearing the N'-(substituted
      benzylidene)-carbohydrazide (11a-e) and N-alkylcarboxamide (13a-g) moieties at
      position-2, were synthesized and screened for their in vitro antitumor activity,
      against seven human cancer cell lines, and for antitrypanosomal and
      antileishmanial activities against Trypanosoma cruzi and Leishmania amazonensis.
      The results indicated that N-methylpiperazyl-6-oxobenzo[4,5]canthine-2
      carboxamide (13f) displayed potent antitumor activity with IC(50) values in the
      range of 1.15-8.46 uM for all cell lines tested. Compounds 13f and 13g bearing an
      N-methylpiperazylcarboxamide and N-morpholylcarboxamide at C-2, respectively,
      showed potent activities towards both Trypanosoma cruzi and Leishmania
      amazonensis parasites, with IC(50) in the range of 0.4 to 16.70 uM.

PMID- 23124561
TI  - Evaluation of models for predicting spray mist diameter for scaling-up of the
      fluidized bed granulation process.
AB  - We evaluated models for predicting spray mist diameter suitable for scaling-up
      the fluidized bed granulation process. By precise selection of experimental
      conditions, we were able to identify a suitable prediction model that considers
      changes in binder solution, nozzle dimension, and spray conditions. We used
      hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC), or
      polyvinylpyrrolidone (PVP) binder solutions, which are commonly employed by the
      pharmaceutical industry. Nozzle dimension and spray conditions for oral dosing
      were carefully selected to reflect manufacturing and small (1/10) scale process
      conditions. We were able to demonstrate that the prediction model proposed by
      Mulhem optimally estimated spray mist diameter when each coefficient was
      modified. Moreover, we developed a simple scale-up rule to produce the same spray
      mist diameter at different process scales. We confirmed that the Rosin-Rammler
      distribution could be applied to this process, and that its distribution
      coefficient was 1.43-1.72 regardless of binder solution, spray condition, or
      nozzle dimension.

PMID- 23124562
TI  - Micellar electrokinetic chromatographic method for mianserin hydrochloride and
      analysis of degradation products by mass spectrometry.
AB  - A simple, stability-indicating micellar electrokinetic chromatography (MEKC)
      method was developed and validated for the analysis of mianserin hydrochloride in
      coated tablets. The method employed (hydroxymethyl)aminomethane (TRIS) 50 mM to
      which sodium dodecyl sulfate (SDS) 50 mM was added at pH 10.6 as the electrolyte
      and the voltage applied was 25 kV. The capillary used was 48.5 cm long (40.0 cm
      effective length and 50.0 um i.d.) and the detection wavelength was 220 nm.
      Tetracycline was used as internal standard. The method was validated in
      accordance with the International Conference on Harmonization (ICH) requirements,
      which involved specificity, linearity, precision, accuracy and robustness. The
      stability-indicating capability of the method was established by enforced
      degradation studies combined with peak purity assessment using photodiode array
      detection. The degradation products formed under photolytic and oxidative
      conditions were investigated by electrospray ionization mass spectrometry. The
      method was linear over the concentration range of 50-130 ug/mL. The method was
      precise as demonstrated by an inter-day and intra-day relative standard deviation
      of less than 2.0%. The proposed validated MEKC method showed recoveries between
      98.16 and 102.80% of the nominal contents. The Plackett-Burman design was applied
      for the robustness test in order to examine potential sources of variability by
      screening a large number of factors in a relatively small number of experiments.

PMID- 23124563
TI  - Synthesis of a key intermediate for the preparation of FTY720 analogs.
AB  - A concise synthesis of a useful intermediate 10 for the preparation of fingolimod
      (FTY-720) analogs was achieved by utilizing a chemoselective Sonogashira reaction
      of trihalobenzene 12 with alkyne 13. The reaction proceeded with high selectivity
      to give alkyne 11 containing the dihalobenzene moiety in good yield. Compound 11
      was converted into intermediate 10 by hydrogenation without reduction of the
      halogen atoms.

PMID- 23124564
TI  - Design space construction of multiple dose-strength tablets utilizing bayesian
      estimation based on one set of design-of-experiments.
AB  - Design spaces for multiple dose strengths of tablets were constructed using a
      Bayesian estimation method with one set of design of experiments (DoE) of only
      the highest dose-strength tablet. The lubricant blending process for theophylline
      tablets with dose strengths of 100, 50, and 25 mg is used as a model
      manufacturing process in order to construct design spaces. The DoE was conducted
      using various Froude numbers (X(1)) and blending times (X(2)) for theophylline
      100-mg tablet. The response surfaces, design space, and their reliability of the
      compression rate of the powder mixture (Y(1)), tablet hardness (Y(2)), and
      dissolution rate (Y(3)) of the 100-mg tablet were calculated using multivariate
      spline interpolation, a bootstrap resampling technique, and self-organizing map
      clustering. Three experiments under an optimal condition and two experiments
      under other conditions were performed using 50- and 25-mg tablets, respectively.
      The response surfaces of the highest-strength tablet were corrected to those of
      the lower-strength tablets by Bayesian estimation using the manufacturing data of
      the lower-strength tablets. Experiments under three additional sets of conditions
      of lower-strength tablets showed that the corrected design space made it possible
      to predict the quality of lower-strength tablets more precisely than the design
      space of the highest-strength tablet. This approach is useful for constructing
      design spaces of tablets with multiple strengths.

PMID- 23124565
TI  - Formulation, characterization and optimization of valsartan self-microemulsifying
      drug delivery system using statistical design of experiment.
AB  - The aim of the present research was to systematically investigate the main,
      interaction and the quadratic effects of formulation variables on the performance
      of self-microemulsifying drug delivery system (SMEDDS) of valsartan using design
      of experiment. A 17-run Box-Behnken design (BBD) with 3-factors and 3-levels,
      including 5 replicates at the centre point, was used for fitting a 2nd-order
      response surface. After the preliminary screening, Labrafil M 2125 CS as oil,
      Tween 20 as surfactant and Capryol 90 as co-surfactant were taken as independent
      variables. The dependent factors (responses) were particle size, polydispersity
      index (PDI), dissolution after 15 min and equilibrium solubility. Coefficients
      were estimated by regression analysis and the model adequacy was checked by an F
      test and the determination coefficient (R(2)). All the responses were optimized
      simultaneously by using desirability function. Our results demonstrated marked
      main and interaction effects of independent factors on responses. The optimized
      formulation consisted of 26.8% (w/w) oil, 60.1% (w/w) surfactant and 13.1% (w/w)
      co-surfactant, and showed average micelle size of 90.7 nm and 0.246 PDI, 91.2%
      dissolution after 15 min and 226.7 mg/g equilibrium solubility. For the optimized
      formulation, predicted value and experimental value were in close agreement.
      After oral administration, the optimized formulation gave more than 2-fold higher
      area under curve (AUC) and about 6-fold higher C(max) in rats than valsartan
      powder (p<0.05). The BBD facilitated in the better understanding of inherent
      relationship of formulation variables with the responses and in the optimization
      of valsartan SMEDDS in relatively time and labor effective manner.

PMID- 23124566
TI  - Validated stability-indicating reversed-phase-HPLC method for simultaneous
      determination of orphenadrine citrate, caffeine and aspirin.
AB  - New, simple, rapid and precise reversed-phase high-performance liquid
      chromatographic method was developed for the simultaneous determination of
      orphenadrine citrate, caffeine and aspirin in presence of aspirin degradation
      products, orphenadrine citrate and caffeine process related impurities, and
      excipients. Good resolution and quantization were achieved on reversed-phase
      column [PhenomenexTM Luna ODS C(18) (25 cm*4.6 mm, 5 um particles)]. Gradient
      elution based on; eluant [A]: 0.1% triethylamine in aqueous potassium dihydrogen
      phosphate buffer (50 mM; pH 3.0), while as, eluant [B]: acetonitrile, at a flow
      rate of 1.5 mL min(-1). UV quantitation was set at 215 nm. Linearity was
      exhibited for orphenadrine citrate, caffeine and aspirin within 0.5-150, 0.5-360
      or 0.7-301 ug mL(-1) ranges, respectively. Satisfactory validation results were
      ascertained in terms of low limits of quantiation (6.33*10(-2)-7.94*10(-2)), mean
      percentage recovery (98.9-101.4%), precision (<2%) and robustness. The proposed
      method was proved to be specific, robust and accurate for the determination of
      cited drugs in pharmaceutical preparations in presence of their degradation
      products.

PMID- 23124567
TI  - Butyrolactone and cycloheptanetrione from mangrove-associated fungus Aspergillus
      terreus.
AB  - A new butyrolactone, 7"-hydroxybutyrolactone III (1) and three new
      cycloheptanetriones, terretrione A-C (2-4), together with five known compounds,
      butyrolactone I, cyclo(Leu-Pro), cyclo(Val-Pro), cyclo(Ile-Pro), cyclo(Phe-Pro),
      were isolated from mangrove-associated marine fungus Aspergillus terreus. The
      structures of these compounds were elucidated on the basis of physical data
      analysis (NMR, high resolution-electrospray ionization (HR-ESI)-MS), especially
      by 2D-NMR techniques. These compounds showed weak cytotoxicity in vitro against
      HCT-8, Bel-7402, BGC-823, A2780 cell lines.

PMID- 23124568
TI  - Speedy and clean hypervalent iodine/nitroxyl radical mediated oxidation of
      alcohols using recyclable adamantane reagent with highly active 2-azaadamantane-N
      oxyl organocatalyst.
AB  - By utilizing a specific solvent and highly active 2-azaadamantane-N-oxyl (AZADO)
      as an organocatalyst, we have improved the recycling protocol of the adamatane
      reagent 1 to be faster and more operationally simple for the hypervalent
      iodine/nitroxyl radical mediated alcohol oxidation. This very mild system can
      efficiently mediate the oxidation of a range of alcohols to carbonyl compounds
      with a broad substrate scope, and after the reactions, the reduced adamantane
      tetraiodide 1', which automatically precipitated from the reaction mixtures as
      the reactions progresses, could be directly recovered by filtration.

PMID- 23124569
TI  - A simple procedure for preparation of N-thiazol, thiadiazol, pyridyl and
      sulfanylamidocantharidinimines analogues and evaluation of their cytotoxicities
      against human HL-60, MCF7, Neuro-2a and A549 carcinoma cell.
AB  - The lab made an effort to prepare some biological active cantharidinimines by
      heating the reactant 1 and 2a-g, 5h-i and 7j-r amines to suitable temperature
      with ethanol to provide 18 N-thiazolyl-, sulfanyl-, aminopyridyl-, bromopyridyl-,
      alkylpyridyl- and hydroxypyridylcantharidinimines 3a-g, 4a-c, 6h-i and 8j-r in
      yield of 4-77% (Chart 1). These cantharidinimine derivatives were tested for
      their capabilities to suppress growth of the human carcinoma cell lines, HL-60,
      MCF7, Neuro-2a and A549, because the incidence rate is more prominent in Asian
      countries than western countries. Compounds 3c-d and 6h-i were found to have some
      antitumor activity in HL-60 but less activity in MCF cell and compounds 8j-l
      displayed some inhibition effects to A549 cell line, but less effect to Neuro-2a
      cell line. Compounds 8m-r had no cytotoxic effect against both cell lines. The
      cytotoxic effects of these cantharidinimine compounds seemed to be better than
      the cantharidinimide compounds which we had mentioned several years ago.

PMID- 23124570
TI  - Preparation of benzo[b]furans having five-membered heterocycles at the 2-position
      and 2-(4-Alkylcarbamoylbuta-1,3-dienyl)benzo[b]furans, and their cysteinyl
      leukotriene receptor (cysLT1, cysLT2) inhibitory activity.
AB  - A series of benzo[b]furan derivatives having a five-membered heterocyclic
      substituent at the 2-position were prepared from 2-(1-chloro-2
      formylvinyl)benzo[b]furans (2) and 2-(4-alkylcarbamoylbuta-1,3
      dienyl)benzo[b]furans. These 2-heterocyclic benzo[b]furans were evaluated for
      their cysteinyl leukotriene receptor (cysLT1, cysLT2) inhibitory activity.
      Several compounds showed moderate inhibition of calcium mobilization in HEK 293T
      cysLT2 or CHO-cysLT1 cells.

PMID- 23124571
TI  - Improved supersaturation and oral absorption of dutasteride by amorphous solid
      dispersions.
AB  - In this study, amorphous solid dispersions containing dutasteride and various
      excipients, manufactured by spray-drying processes, were characterized to
      determine the effects on their ability to form supersaturated solutions and to
      identify the effects of supersaturation on increasing the bioavailability of
      dutasteride. The excipients included Eudragit E, hydroxypropyl-beta-cyclodextrin
      (HP-beta-CD), hydroxypropyl cellulose (HPC), hydroxypropylmethyl cellulose
      (HPMC), and polyvinylpyrrolidone (PVP K30). A solid dispersion with Eudragit E
      displayed a high maximum supersaturation with extended supersaturation, compared
      with a water-soluble polymer. The maximum concentration and the degree of
      supersaturation increased in the following order: PVP K30<HP-beta
      CD=HPC<HPMC<Eudragit E. Oral drug absorption of solid dispersions was obviously
      higher when compared with micronized raw material and physical mixtures, in the
      following order: HPC<HPMC<Eudragit E. In fact, the AUC(0->24 h) and C(max) of
      dutasteride increased with supersaturation concentration. These results suggest
      that amorphous solid dispersions containing Eudragit E, formed by a spray-drying
      process, offer enhanced supersaturation characteristics, leading to increased
      oral absorption of dutasteride.

PMID- 23124572
TI  - Technical note: a novel geometric morphometric approach to the study of long bone
      shape variation.
AB  - Procrustes-based geometric morphometrics (GM) is most often applied to problems
      of craniofacial shape variation. Here, we demonstrate a novel application of GM
      to the analysis of whole postcranial elements in a study of 77 hominoid tibiae.
      We focus on two novel methodological improvements to standard GM approaches: 1)
      landmark configurations of tibiae including 15 epiphyseal landmarks and 483
      semilandmarks along articular surfaces and muscle insertions along the tibial
      shaft and 2) an artificial affine transformation that sets moments along the
      shaft equal to the sum of the moments estimated in the other two anatomical
      directions. Diagrams of the principal components of tibial shapes support most
      differences between human and non-human primates reported previously. The
      artificial affine transformation proposed here results in an improved clustering
      of the great apes that may prove useful in future discriminant or clustering
      studies. Since the shape variations observed may be related to different
      locomotor behaviors, posture, or activity patterns, we suggest that this method
      be used in functional analyses of tibiae or other long bones in modern
      populations or fossil specimens.

PMID- 23124574
TI  - [Editorial: Pharmazie in unserer Zeit 6/2012].

PMID- 23124573
TI  - Tumor location and nature of lymphatic vessels are key determinants of cancer
      metastasis.
AB  - Tumor metastasis to lymph nodes is a key indicator of patient survival, and is
      enhanced by the neo-lymphatics induced by tumor-secreted VEGF-C or VEGF-D, acting
      via VEGFR-3 signalling. These targets constitute important avenues for anti
      metastatic treatment. Despite this new understanding, clinical observations
      linking metastasis with tumor depth or location suggest that lymphangiogenic
      growth factors are not the sole determinants of metastasis. Here we explored the
      influence of tumor proximity to lymphatics capable of responding to growth
      factors on nodal metastasis in a murine VEGF-D over-expression tumor model. We
      found that primary tumor location profoundly influenced VEGF-D-mediated lymph
      node metastasis: 89 % of tumors associated with the flank skin metastasised, in
      contrast with only 19 % of tumors located more deeply on the body wall (p <
      0.01). Lymphatics in metastatic tumors arose from small lymphatics, and displayed
      distinct molecular and morphological profiles compared with those found in normal
      lymphatics. Smaller lymphatic subtypes were more abundant in skin (2.5-fold, p <
      0.01) than in body wall, providing a richer source of lymphatics for VEGF-D(+)
      skin tumors, a phenomenon also confirmed in human samples. This study shows that
      the proximity of a VEGF-D(+) primary tumor to small lymphatics is an important
      determinant of metastasis. These observations may explain why tumor location
      relative to the lymphatic network is prognostically important for some human
      cancers.

PMID- 23124575
TI  - Clopidogrel treatment and the incidence and severity of community acquired
      pneumonia in a cohort study and meta-analysis of antiplatelet therapy in
      pneumonia and critical illness.
AB  - Platelet activation results in the release and upregulation of mediators
      responsible for immune cell activation and recruitment, suggesting that platelets
      play an active role in immunity. Animal models and retrospective data have
      demonstrated benefit of antiplatelet therapy on inflammatory mediator expression
      and clinical outcomes. This study sought to characterize effects of clopidogrel
      on the incidence and severity of community-acquired pneumonia (CAP). A
      retrospective cohort study was conducted of Kentucky Medicaid patients (2001
      2005). The exposed cohort consisted of patients receiving at least six
      consecutive clopidogrel prescriptions; the non-exposed cohort was comprised of
      patients not prescribed clopidogrel. Primary endpoints included incidence of CAP
      and inpatient treatment. Secondary severity endpoints included mortality,
      intensive care unit admission, mechanical ventilation, sepsis, and acute
      respiratory distress syndrome/acute lung injury. CAP incidence was significantly
      greater in the exposed cohort (OR 3.39, 95% CI 3.27-3.51, p < 0.0001) that
      remained after adjustment (OR 1.48, 95% CI 1.41-1.55, p < 0.0001). Inpatient
      treatment was more common in the exposed cohort (OR 1.96, 95% CI 1.85-2.07, p <
      0.0001), but no significant difference remained after adjustment. Trends favoring
      the exposed cohort were found for the secondary severity endpoints of mechanical
      ventilation (p = 0.07) and mortality (p = 0.10). Pooled analysis of published
      studies supports these findings. While clopidogrel use may be associated with
      increased CAP incidence, clopidogrel does not appear to increase--and may reduce-
      its severity among inpatients. Because this study was retrospective and could not
      quantify all variables (e.g., aspirin use), these findings should be explored
      prospectively.

PMID- 23124576
TI  - Reducing radiation exposure using commonly available objects.
AB  - OBJECTIVES: One and a half years have passed since the Fukushima Daiichi nuclear
      power plant disaster. The environmental radiation dose rate was not critical, but
      an existing exposure situation has been identified in a large part of Fukushima
      Prefecture. Although people continue to live and work in the contaminated area,
      they are not provided with sufficient information to reduce their exposure to
      radiation by themselves. In this study, we attempt to evaluate the efficiency of
      radiation shielding by using everyday items widely available to people. METHODS:
      NaI scintillation and Geiger-Muller survey meters were used to measure the
      radiation dose of (1) contaminated soil and (2) soil covered with commonly
      available items. RESULTS: In the soil at a depth of 10 cm from the surface, the
      radiation dose rate decreased from 3.36 to 0.65 MUSv/h, and the count rate
      decreased from 3,120 to 352 cpm. Both the radiation dose rate and count rate
      reduced when the soil was covered with everyday items, such as a magazine more
      than 20 mm thick, a polystyrene foam board, and a wooden board of the same
      thickness. CONCLUSIONS: To protect residents from unnecessary radiation exposure
      in the existing exposure situation, covering contaminated soil with a wooden
      board or a magazine, either of them 20 mm thick, is useful to reduce the
      radiation dose.

PMID- 23124577
TI  - microRNA changes in the dorsal horn of the spinal cord of rats with chronic
      constriction injury: A TaqMan(r) Low Density Array study.
AB  - Elucidation of the mechanisms underlying neuropathic pain is expected to aid in
      the discovery and selection of effective therapeutic methods. Currently, microRNA
      (miRNA) is thought to play an important role in the development and maintenance
      of the nervous system. We, therefore, hypothesized that miRNAs are involved in
      neuropathic pain, and investigated this possibility by analyzing miRNA expression
      in the dorsal horn of the spinal cord in a chronic constriction injury (CCI) rat
      model using the TaqMan(r) Low Density Array (TLDA). Neuropathic pain model rats
      were produced by CCI induced by ligation of the sciatic nerve. The miRNA
      expression in the dorsal horn of the spinal cord was analyzed in Day 0 rats, with
      no sciatic nerve ligation or sham operation, Day 7 rats, examined 7 days after
      sciatic nerve ligation or sham operation, and Day 14 rats, examined 14 days after
      sciatic nerve ligation or sham operation using TLDA. In this study, 111 miRNAs
      were significantly regulated in CCI rats in both the Day 7 and Day 14 groups
      compared with sham rats in both groups. Of these 111, there were 75 miRNAs
      (67.6%) that had been analyzed in previous reports and 36 miRNAs (32.4%) related
      to the development of tumors of the nervous system and neurodegenerative
      diseases. Certain miRNAs were reported to be related to neuropathic pain; miR
      500, -221 and -21. The expression levels of a large number of miRNAs in the
      dorsal horn of the spinal cord in CCI rats changed. These results provide a step
      toward elucidation of the mechanisms underlying neuropathic pain.

PMID- 23124578
TI  - Total synthesis of (+)-trans-trikentrin A.
AB  - Several syntheses have already been reported for cis-trikentrins and herbindoles,
      which are indole alkaloids unsubstituted at the C2 and C3 positions that bear a
      trans-1,3-dimethylcyclopentyl unit. Herein, we describe the first asymmetric and
      stereoselective synthesis of the more challenging trans-trikentrin A as its
      naturally occurring isomer. Different approaches were investigated and the
      strategy of choice was a combination of an enzymatic kinetic resolution and a
      thallium(III)-mediated ring contraction. The antiproliferative activities of the
      natural product and related intermediates have been tested against human tumor
      cell lines, leading to the discovery of new compounds with potent antitumor
      activity.

PMID- 23124579
TI  - Communicating synovial pseudocyst in small joint of the hand assessed by
      ultrasound.

PMID- 23124580
TI  - Seizures in juvenile Huntington's disease: frequency and characterization in a
      multicenter cohort.
AB  - Little is known about the epilepsy that often occurs in the juvenile form of
      Huntington's disease (HD), but is absent from the adult-onset form. The primary
      aim of this study was to characterize the seizures in juvenile HD (JHD) subjects
      with regard to frequency, semiology, defining EEG characteristics, and response
      to antiepileptic agents. A multicenter, retrospective cohort was identified by
      database query and/or chart review. Data on age of HD onset, primary HD
      manifestations, number of CAG repeats, the presence or absence of seizures,
      seizure type(s), antiepileptic drugs used, subjects' response to antiepileptic
      drugs (AEDs), and EEG results were assembled, where available. Ninety subjects
      with genetically confirmed JHD were included. Seizures were present in 38% of
      subjects and were more likely to occur with younger ages of HD onset. Generalized
      tonic-clonic seizures were the most common seizure type, followed by tonic,
      myoclonic, and staring spells. Multiple seizure types commonly occurred within
      the same individual. Data on EEG findings and AED usage are presented. Seizure
      risk in JHD increases with younger age of HD onset. Our ability to draw firm
      conclusions about defining EEG characteristics and response to AEDs was limited
      by the retrospective nature of the study. Future prospective studies are
      required.

PMID- 23124581
TI  - Sexual mixing, drug exchanges, and infection risk among long-haul truck drivers.
AB  - Despite extensive anecdotal evidence on US long-haul truckers' risk interactions
      on the road, links between their sexual mixing and drug exchanges and their
      potential risk for STI/BBI acquisition and dissemination remain insufficiently
      documented. Grounded in social ecological theories and multi method ethnographic
      data, this paper examines the sexual transactions and drug exchanges of key
      members of US trucker risk networks within diverse trucking milieux. Research has
      uncovered four key trucker-centered populations and their diverse risk exchanges:
      (a) straight male truckers who engage in casual sex with women; (b) female
      sexworkers (known as "lot lizards") who solicit truckers; (c) intermediaries who
      broker sex and drug exchanges between truckers, drug dealers and sexworkers; and
      (d) male truckchasers who cruise for truckers in physical and virtual milieux to
      engage in sex. Concurrent sexual partnerships of truckers have the potential to
      amplify initial infections by linking individuals of disparate epidemiological
      settings, thereby enabling pathogens to travel rapidly and efficiently to
      disparate regions. The comprehensive delineation of the role of long-haul
      trucking in potential disease spread is required for the development of effective
      STI/HIV prevention programs for populations of interest.

PMID- 23124583
TI  - Microfluidic trap-and-release system for lab-on-a-chip-based studies on giant
      vesicles.
AB  - We present a microfluidic array that allows lab-on-a-chip-based studies on
      hundreds of giant vesicles through immobilization, engineering and release of the
      vesicles. Real-time observations of the vesicular response are reported. This
      trap-and-release system is also used to efficiently narrow the size distribution
      of the vesicle population. In addition, it can be applied to a wide range of
      deformable objects.

PMID- 23124582
TI  - Coordinating research and practice: challenges testing messages to increase
      medical reserve corps participation in local health department activities.
AB  - Local health departments (LHDs) increasingly depend on volunteers, often Medical
      Reserve Corps (MRC) volunteers, to assist with a variety of functions. While LHDs
      have extensive lists of volunteers, only about 10 % are actively involved in LHD
      activities. Psychological literature has shown that well-designed messages can
      motivate behavior among individuals. Key to this theory is the concept of
      "framing," defined as the influence the characterization of an issue can have on
      its understanding. Research has been conducted on how to frame and disseminate
      both political and public health messages to alter individual behavior. We aimed
      to design and test appropriate evidence-based messages to increase volunteer
      participation rates in LHD flu clinics. After inviting over 900 MRC units to
      participate during the 2011-2012 influenza season, five were able to collect and
      report data to the research team. Using a randomized trial design, we tested
      messages among the five participating MRC units consisting of a total of 2,020
      volunteers. Chi Square analysis showed no difference in attendance between those
      who received either of the test messages versus the control message (p = .305).
      Our small sample size of MRC units likely biased our sample and reduced the
      external validity of our study. Our experience in conducting research with MRC
      coordinators and volunteers highlights the challenges of conducting research with
      practitioners who lack the time, infrastructure and resources necessary to work
      with researchers. There is a strong need for more supportive infrastructure for
      conducting research with practitioners.

PMID- 23124584
TI  - Endoloop ligation technique for prolapsed pedunculated submucous uterine myoma:
      utility and reliability.
AB  - PURPOSE: We use a non-surgical endoloop snare technique to remove prolapsed
      pedunculated submucous uterine myomas under the concept that ligating the pedicle
      causes tumor necrosis and natural elimination of the tumor. We evaluated our
      method on the basis of clinical outcomes. METHODS: For pertinent clinical data,
      we reviewed the hospital records of 11 patients treated by our new method between
      July 2009 and 2010 and followed up for 22-31 months. RESULTS: Patients' mean age
      was 40.9 years, and the mean hemoglobin level was 10.6 g/dl. None required urgent
      hospitalization, blood transfusion, or laparotomy. The tumors were eliminated
      naturally or removed by cutting necrotic pedicle within 4-11 days. One patient
      required a second endoloop application. Another one patient required follow-up
      surgery for a second submucous myoma, adenomyosis, and persistent hypermenorrhea.
      CONCLUSIONS: Endoloop ligation is feasible for eliminating prolapsed pedunculated
      submucous myoma. It is simple and safe and can be performed in the outpatient
      setting.

PMID- 23124585
TI  - Aortic pulse wave velocity measurements with undersampled 4D flow-sensitive MRI:
      comparison with 2D and algorithm determination.
AB  - PURPOSE: To compare pulse wave velocity (PWV) measurements obtained from radially
      undersampled 4D phase-contrast magnetic resonance imaging (PC-MRI) with 2D PC
      measurements and to evaluate four PWV algorithms. MATERIALS AND METHODS: PWV was
      computed from radially undersampled 3D, 3-directionally velocity-encoded PC-MRI
      (4D) acquisitions performed on a 3T MR scanner in 18 volunteers. High temporal
      resolution 2D PC scans serving as a reference standard were available in 14
      volunteers. Four PWV algorithms were tested: time-to-upstroke (TTU), time-to-peak
      (TTP), time-to-foot (TTF), and cross-correlation (XCorr). Bland-Altman analysis
      was used to determine inter- and intraobserver reproducibility and to compare
      differences between algorithms. Differences in age and PWV measurements were
      analyzed with Student's t-tests. The variability of age-corrected data was
      assessed with a Brown-Forsythe analysis of variance (ANOVA) test. RESULTS: 2D
      (4.6-5.3 m/s) and 4D (3.8-4.8 m/s) PWV results were in agreement with previously
      reported values in healthy subjects. Of the four PWV algorithms, the TTU, TTF,
      and XCorr algorithms gave similar and reliable results. Average biases of +0.30
      m/s and -0.01 m/s were determined for intra- and interobserver variability,
      respectively. The Brown-Forsythe test revealed that no differences in variability
      could be found between 2D and 4D PWV measurements. CONCLUSION: 4D PC-MRI with
      radial undersampling provides reliable and reproducible measurements of PWV. TTU,
      TTF, and XCorr were the preferred PWV algorithms.

PMID- 23124586
TI  - Variation in neuronal differentiation of a newly isolated mouse embryonic stem
      cell line: a detailed immunocytochemistry study.
AB  - Neural precursor differentiation from mouse ES (embryonic stem) cells have been
      demonstrated using EB (embryoid body), co-culture on stromal feeder layers, and
      in the absence of external inducing signals. Most of available mouse ES cell
      original research articles have worked with only six different cell lines. Our
      goals were to isolate one new mouse ES lineage, and perform a detailed
      immunocytochemistry study during neural differentiation, making use of an EB
      strategy protocol following the generation of neural progenitors, glial cells and
      postmitotic neurons. The dynamics of differentiation of ES cell derived neuronal
      precursors into differentiated glia cells and neurons were followed in vitro and
      correlated to exposure to specific elements of feeder medium. Morphological
      aspects of generated cellular types, including its immunocytochemical expression
      of differentiation markers were studied. Immuno-positivity against beta-III
      tubulin, PGP and TH (tyrosine hydroxylase) was observed from stage I.
      Approximately 80% of cells were positive for TH at stage I. The first glial cell
      type appears in stage III. TH, PGP or beta-III tubulin-positive cells with
      neuronal typical morphology only being seen in stage III when TH-positive cells
      corresponded to approximately 12% of total cells. Variations among other
      literature findings can be explained by the choice we made to use a newly
      isolated ES cell line. As colonies may behave differently during neuronal
      differentiation, it reinforces the necessity of studying original ES cell lines.

PMID- 23124587
TI  - Transanal access for rectal tumors: the simultaneous use of a flexible endoscope
      and SILS.
AB  - The authors report that TEM with a single-incision laparoscopic surgery (SILS)
      port can be facilitated by the use of a colonoscope instead of a conventional
      laparoscopic camera. The colonoscope can be inserted through one of the SILS
      channels and has the added benefit of flexibility, insufflation, irrigation,
      suction, and an operative port. 

PMID- 23124588
TI  - The influence of family stability on self-control and adjustment.
AB  - OBJECTIVES: The aim of the present study was to replicate previous evidence for a
      model in which self-control mediates the relationship between family stability
      and internalizing symptoms, and to evaluate a similar model with regard to
      externalizing problems. METHOD: Participants were 155 female and 134 male
      undergraduates--mean age of 19.03 years. Participants completed measures of
      stability in the family of origin (Stability of Activities in the Family
      Environment), self-control (Self-Control scale), current externalizing (Adult
      Self-Report), and internalizing problems (Beck Depression Inventory II and Beck
      Anxiety Inventory). RESULTS: Multiple regression analyses largely support the
      proposed model for both the externalizing and internalizing domains. CONCLUSIONS:
      Family stability may foster the development of self-control and, in turn, lead to
      positive adjustment.

PMID- 23124589
TI  - A simple eccentric stirred tank mini-bioreactor: mixing characterization and
      mammalian cell culture experiments.
AB  - In industrial practice, stirred tank bioreactors are the most common mammalian
      cell culture platform. However, research and screening protocols at the
      laboratory scale (i.e., 5-100 mL) rely primarily on Petri dishes, culture
      bottles, or Erlenmeyer flasks. There is a clear need for simple-easy to assemble,
      easy to use, easy to clean-cell culture mini-bioreactors for lab-scale and/or
      screening applications. Here, we study the mixing performance and culture
      adequacy of a 30 mL eccentric stirred tank mini-bioreactor. A detailed mixing
      characterization of the proposed bioreactor is presented. Laser induced
      fluorescence (LIF) experiments and computational fluid dynamics (CFD)
      computations are used to identify the operational conditions required for
      adequate mixing. Mammalian cell culture experiments were conducted with two
      different cell models. The specific growth rate and the maximum cell density of
      Chinese hamster ovary (CHO) cell cultures grown in the mini-bioreactor were
      comparable to those observed for 6-well culture plates, Erlenmeyer flasks, and 1
      L fully instrumented bioreactors. Human hematopoietic stem cells were
      successfully expanded tenfold in suspension conditions using the eccentric mini
      bioreactor system. Our results demonstrate good mixing performance and suggest
      the practicality and adequacy of the proposed mini-bioreactor.

PMID- 23124590
TI  - Net carbon sequestration potential and emissions in home lawn turfgrasses of the
      United States.
AB  - Soil analyses were conducted on home lawns across diverse ecoregions of the U.S.
      to determine the soil organic carbon (SOC) sink capacity of turfgrass soils.
      Establishment of lawns sequestered SOC over time. Due to variations in
      ecoregions, sequestration rates varied among sites from 0.9 Mg carbon (C) ha(-1)
      year(-1) to 5.4 Mg C ha(-1) year(-1). Potential SOC sink capacity also varied
      among sites ranging from 20.8 +/- 1.0-96.3 +/- 6.0 Mg C ha(-1). Average
      sequestration rate and sink capacity for all sites sampled were 2.8 +/- 0.3 Mg C
      ha(-1) year(-1) and 45.8 +/- 3.5 Mg C ha(-1), respectively. Additionally, the
      hidden carbon costs (HCC) due to lawn mowing (189.7 kg Ce (carbon equivalent) ha(
      1) year(-1)) and fertilizer use (63.6 kg Ce ha(-1) year(-1)) for all sites
      totaled 254.3 kg Ce ha(-1) year(-1). Considering home lawn SOC sink capacity and
      HCC, mean home lawn sequestration was completely negated 184 years post
      establishment. The potential SOC sink capacity of home lawns in the U.S. was
      estimated at 496.3 Tg C, with HCC of between 2,504.1 Gg Ce year(-1) under low
      management regimes and 7551.4 Gg Ce year(-1) under high management. This leads to
      a carbon-positive system for between 66 and 199 years in U.S. home lawns. More
      efficient and reduction of C-intensive maintenance practices could increase the
      overall sequestration longevity of home lawns and improve their climate change
      mitigation potential.

PMID- 23124591
TI  - Electrical stimulation modulates osteoblast proliferation and bone protein
      production through heparin-bioactivated conductive scaffolds.
AB  - Electrical fields are known to interact with human cells. This principle has been
      explored to regulate cellular activities for bone tissue regeneration. In this
      work, Saos-2 cells were cultured on conductive scaffolds made of biodegradable
      poly(L-lactide) and the heparin-containing, electrically conducting polypyrrole
      (PPy/HE) to study their reaction to electrical stimulation (ES) mediated through
      such scaffolds. Both the duration and intensity of ES enhanced cell
      proliferation, generating a unique electrical intensity and temporal "window"
      within which osteoblast proliferation was upmodulated in contrast to the
      downmodulation or ineffectiveness in other ES regions. The favourable ES
      intensity (200 mV/mm) was further investigated in terms of the gene activation
      and protein production of two important osteoblast markers characterised by
      extracellular matrix maturation and mineralisation, that is alkaline phosphatase
      (ALP) and osteocalcin (OC). Both genes were found activated and the relevant
      protein production increased significantly following ES. In contrast, ES in the
      down-modulation region (400 mV/mm) suppressed the production of both ALP and OC.
      This work demonstrated that important osteoblast markers can be modulated with
      specific ES parameters mediated through conductive polymer substrates, providing
      a unique strategy for bone tissue engineering.

PMID- 23124592
TI  - Overexpression of oxidored-nitro domain containing protein 1 inhibits human
      nasopharyngeal carcinoma and cervical cancer cell proliferation and induces
      apoptosis: Involvement of mitochondrial apoptotic pathways.
AB  - Oxidored-nitro domain containing protein 1 (NOR1) is a novel member of the
      nitroreductase family that was first isolated as a tumor suppressor gene from
      human nasopharyngeal carcinoma (NPC). However, the role of NOR1 gene dysfunction
      in human cancers has not been addressed. We analyzed the expression of NOR1 in
      various human cancer and benign tissue specimens and found significant
      downregulation in nine types of cancer compared with corresponding non-tumor
      tissues. The recombinant expression vector pCDNA3.1-myc-his-NOR1 was constructed
      and transfected into human NPC 6-10B nasopharyngeal cancer and HeLa cervical
      cancer (CCA) cells. We found that stable NOR1 overexpression resulted in
      suppression of 6-10B and HeLa cell proliferation and led to S phase cell cycle
      arrest. In addition, NOR1 upregulation enhanced apoptosis in pCDNA3.1-myc-his
      NOR1 stably transfected cells, and it also altered the expression of proteins
      involved in the mitochondria-dependent apoptotic pathway. Furthermore, we also
      found that the NOR1 protein is a cytoplasmic protein that is partially localized
      in the mitochondria and endoplasmic reticulum. Therefore, NOR1 is an important
      tumor suppressor gene associated with NPC and CCA and may play antitumor roles by
      inhibiting proliferation, preventing colony formation, and promoting the
      apoptosis of tumor cells via the mitochondrial-dependent apoptotic pathway.
      However, the precise mechanism behind the NOR1 antitumor effects needs to be
      investigated further.

PMID- 23124593
TI  - Victims and survivors: stable isotopes used to identify migrants from the Great
      Irish Famine to 19th century London.
AB  - Historical evidence documents mass migration from Ireland to London during the
      period of the Great Irish Famine of 1845-52. The rural Irish were reliant on a
      restricted diet based on potatoes but maize, a C(4) plant, was imported from the
      United States of America in 1846-47 to mitigate against Famine. In London, Irish
      migrants joined a population with a more varied diet. To investigate and
      characterize their diet, carbon and nitrogen isotope ratios were obtained from
      bone collagen of 119 and hair keratin of six individuals from Lukin Street
      cemetery, Tower Hamlets (1843-54), and bone collagen of 20 individuals from the
      cemetery at Kilkenny Union Workhouse in Ireland (1847-51). A comparison of the
      results with other contemporaneous English populations suggests that Londoners
      may have elevated delta(15) N compared with their contemporaries in other cities.
      In comparison, the Irish group have lower delta(15) N. Hair analysis combined
      with bone collagen allows the reconstruction of perimortem dietary changes. Three
      children aged 5-15 years from Kilkenny have bone collagen delta(13) C values that
      indicate consumption of maize (C(4)). As maize was only imported into Ireland in
      quantity from late 1846 and 1847, these results demonstrate relatively rapid bone
      collagen turnover in children and highlight the importance of age-related bone
      turnover rates, and the impact the age of the individual can have on studies of
      short-term dietary change or recent migration. Stable light isotope data in this
      study are consistent with the epigraphic and documentary evidence for the
      presence of migrants within the London cemetery.

PMID- 23124594
TI  - Absolute quantitation of stevioside and rebaudioside A in commercial standards by
      quantitative NMR.
AB  - The extract prepared from the leaves of Stevia rebaudiana BERTONI (Asteraceae)
      contains sweet steviol glycosides, mainly stevioside and rebaudioside A. Highly
      purified stevia extracts have become popular worldwide as a natural, low-calorie
      sweetener. They contain various types of steviol glycosides, and their main
      components are stevioside and rebaudioside A. The content of each steviol
      glycoside is quantified by comparing the ratios of the molecular weights and the
      chromatographic peak areas of the samples to those of stevioside or rebaudioside
      A standards of the Food and Agriculture Organization of the United Nations
      (FAO)/World Health Organization (WHO) Joint Expert Committee on Food Additives
      (JECFA) and other specifications. However, various commercial standard reagents
      of stevioside and rebaudioside A are available. Their purities are different and
      their exact purities are not indicated. Therefore, the measured values of
      stevioside and rebaudioside A contained in a sample vary according to the
      standard used for the quantification. In this study, we utilized an accurate
      method, quantitative NMR (qNMR), for determining the contents of stevioside and
      rebaudioside A in standards, with traceability to the International System of
      Units (SI units). The purities of several commercial standards were determined to
      confirm their actual values.

PMID- 23124595
TI  - In situ gel-to-crystal transition and synthesis of metal nanoparticles obtained
      by fluorination of a cyclic beta-aminoalcohol gelator.
AB  - A new fluorinated version of a cyclic beta-aminoalcohol gelator derived from
      1,2,3,4-tetrahydroisoquinoline is presented. The gelator is able to gel various
      nonprotic solvents through OH???N hydrogen bonds and additional CH???F
      interactions due to the introduction of fluorine. A bimolecular lamellar
      structure is formed in the gel phase, which partly preserves the pattern of
      molecular organization in the single crystal. The racemate of the chiral gelator
      shows lower gelation ability than its enantiomer because of a higher tendency to
      form microcrystals, as shown by X-ray diffraction analysis. The influence of
      fluorination on the self-assembly of the gelator and the properties of the gel
      was investigated in comparison to the original fluorine-free gel system. The
      introduction of fluorine brings two new features. The first is good recognition
      of o-xylene by the gelator, which induces an in situ transition from gels of o
      xylene and of an o-xylene/toluene mixture to identical single crystals with
      unique tubular architecture. The second is the enhanced stability of the toluene
      gel towards ions, including quaternary ammonium salts, which enables the
      preparation of a stable toluene gel in the presence of chloroaurate or
      chloroplatinate. The gel system can be used as a template for the synthesis of
      spherical gold nanoparticles with a diameter of 5 to 9 nm and wormlike platinum
      nanostructures with a diameter of 2 to 3 nm and a length of 5 to 12 nm. This is
      the first example of a synthesis of platinum nanoparticles in an organogel
      medium. Therefore, the appropriate introduction of a fluorine atom and
      corresponding nonbonding interactions into a known gelator to tune the properties
      and functions of a gel is a simple and effective tactic for design of a gel
      system with specific targets.

PMID- 23124596
TI  - Value of pelvic sonography in the diagnosis of various forms of precocious
      puberty in girls.
AB  - PURPOSE: To evaluate the role of pelvic sonography (US) in the diagnosis and
      differentiation of various forms of precocious puberty in girls, and to explore
      reliable cutoff points of pelvic US measurements for differentiating between
      these conditions. METHODS: Uterine length, uterine cross-sectional area, uterine
      volume, fundocervical ratio, and ovarian volumes of 143 healthy girls were
      compared with those of 125 girls with different forms of sexual precocity.
      Ovaries were morphologically classified as homogenous, paucicystic, multicystic,
      macrocystic, and isolated cystic. RESULTS: Almost all US measurements of girls
      with central precocious puberty in the 0- to 8-year age group were significantly
      increased compared with controls and girls with premature thelarche and
      adrenarche (p < 0.05, except for ovarian volumes in premature thelarche group),
      whereas no statistically significant difference was found in the 8- to 10-year
      group (p > 0.05). Ovarian morphology distributions did not differ significantly
      between patient subgroups, but all had more mature forms compared with controls.
      Due to the wide overlap between the measurements, no reliable cutoff points could
      be determined by charting receiver operating characteristics curves. CONCLUSIONS:
      Pelvic US can improve the diagnosis of central precocious puberty in girls of 0-8
      years of age but provides no reliable type differentiation alone. It provides no
      valuable information for this diagnosis in girls of 8-10 years of age.

PMID- 23124597
TI  - Functional analysis of Spodoptera frugiperda nucleopolyhedrovirus late expression
      factors in Sf9 cells.
AB  - We used transient expression assays to assess the function of the baculovirus
      Spodoptera frugiperda M nucleopolyhedrovirus (SfMNPV) homologs of Autographa
      californica MNPV (AcMNPV) factors involved in late gene expression (lefs), in the
      Sf9 insect cell-line, which is permissive for both viruses. It is well
      established that nineteen AcMNPV lefs support optimal levels of activity from a
      late promoter-reporter gene cassette in this assay. A subgroup of SfMNPV lefs
      predicted to function in transcription-specific events substituted the
      corresponding AcMNPV lefs very efficiently. When all SfMNPV lefs were assayed,
      including replication lefs, activity was low, but addition of two AcMNPV lefs not
      encoded in SfMNPV genome, resulted in augmented reporter activity. SfMNPV IE-1
      was able to activate an early promoter cis-linked to an hr-derived element from
      SfMNPV but not from AcMNPV. However, the level of early promoter activation with
      SfMNPV IE-1 was lower compared to AcMNPV IE-1.

PMID- 23124599
TI  - Outcome-dependent coactivation of lip and tongue primary somatosensory
      representation following hypoglossal-facial transfer after peripheral facial
      palsy.
AB  - A hypoglossal-facial transfer is a common surgical strategy for reanimating the
      face after persistent total hemifacial palsy. We were interested in how motor
      recovery is associated with cortical reorganization of lip and tongue
      representation in the primary sensorimotor cortex after the transfer. Therefore,
      we used functional magnetic resonance imaging (fMRI) in 13 patients who underwent
      a hypoglossal-facial transfer after unilateral peripheral facial palsy. To
      identify primary motor and somatosensory tongue and lip representation sites, we
      measured repetitive tongue and lip movements during fMRI. Electromyography (EMG)
      of the perioral muscles during tongue and lip movements and standardized
      evaluation of lip elevation served as outcome parameters. We found an association
      of cortical representation sites in the pre- and postcentral gyrus (decreased
      distance of lip and tongue representation) with symmetry of recovered lip
      movements (lip elevation) and coactivation of the lip during voluntary tongue
      movements (EMG-activity of the lip during tongue movements). Overall, our study
      shows that hypoglossal-facial transfer resulted in an outcome-dependent cortical
      reorganization with activation of the cortical tongue area for restituded
      movement of the lip.

PMID- 23124598
TI  - Global microRNA profiling in favorable prognosis subgroups of cancer of unknown
      primary (CUP) demonstrates no significant expression differences with metastases
      of matched known primary tumors.
AB  - No data exist on biologic differences between Cancer of unknown primary (CUP) and
      metastatic solid tumors of known primary site. We assigned a primary tissue of
      origin in 40 favorable CUP patients (A: serous peritoneal carcinomatosis n = 14,
      B: axillary adenocarcinoma n = 8, C: upper squamous cervical adenopathy n = 18)
      by means of a 64-microRNA assay. Subsequently, we profiled the expression of 733
      microRNAs (miRs) in the CUP cases and compared results with metastases from 20
      ovarian carcinomas, 10 breast adenocarcinomas, 20 squamous head neck or lung
      tumors. In the Peritoneal CUP versus Ovarian (Known Primary Metastases) KPM
      comparison, a total of 12 miR were significantly differentially expressed: higher
      than twofold expression difference in CUP was seen only for miR-513a-5p (3.7-fold
      upregulated) and miR-483-5p (2.5-fold upregulated), while miR-708 exhibited a
      twofold downregulation. In the Breast CUP versus Breast KPM comparison, only miR
      29c that were downregulated in CUP by 2.7-fold satisfied the FDR threshold. miR
      30e and miR-27b, downregulated in ovarian CUPs versus KPMs, were also non
      significantly downregulated in breast CUP by 2.0- and 1.4-fold respectively. Six
      miRs, which belong to the 17-92 oncocluster showed a trend of upregulation in
      Breast CUP versus Breast KPM cases. A CUP signature remains elusive.

PMID- 23124600
TI  - Ascites, hydrocolpos, hydrometrocolpos with normal amniotic fluid in a fetus with
      partial urorectal septum malformation sequence.
AB  - Urorectal septum malformation sequence (URSMS) describes a range of anatomic
      anomalies in the urogenital and lower gastrointestinal organs caused by
      incomplete urorectal membrane septation and persistence of the cloacal membrane.
      Partial URSMS is a milder version characterized by a single perineal opening. We
      report a case of partial URSMS that associated an intact Mullerian system, single
      perineal opening, blind colon, imperforate anus and vagina, urethrovaginal
      connection, and ambiguous genitalia. Hydrocolpos, hydrometrocolpos, and ascites
      were seen in utero and confirmed on postnatal surgery. This case describes the
      changes in sonographic findings that evolved throughout the gestation.

PMID- 23124601
TI  - No difference in anterior knee pain between a fixed and a mobile posterior
      stabilized total knee arthroplasty after 7.9 years.
AB  - PURPOSE: The presence of anterior knee pain remains one of the major complaints
      following total knee arthroplasty (TKA). Since the introduction of the mobile
      TKA, many studies have been performed and only a few show a slight advantage for
      the mobile. In our short-term follow-up study, we found less anterior knee pain
      in the posterior stabilized mobile knees compared to the posterior stabilized
      knees. The concept of self-alignment and the results from our short-term study
      led us to form the hypothesis that the posterior stabilized mobile knee leads to
      a lower incidence of anterior knee pain compared to the posterior stabilized
      fixed knee. This study was designed to see whether this difference remains after
      7.9 years in the follow-up. A secondary line of enquiry was to see whether one
      was superior to the other regarding pain, function, quality of life and survival.
      METHODS: This current report is a 6-10-year (median 7.9 years) follow-up study of
      the remaining 69 patients with a cemented three-component TKA for osteoarthritis
      in a prospective, randomized, double-blinded clinical trial. RESULTS: In the
      posterior stabilized group, five of the 40 knees (13%) versus five of the 29
      posterior stabilized mobile group (17%) experienced anterior knee pain. No
      differences were observed with regard to ROM, VAS, Oxford 12-item knee
      questionnaire, SF-36, HSS patella, Kujala or the AKSS score. Patients with
      anterior knee pain reported more pain, lower levels of the AKSS, HSS patella and
      the Kujala scores than the patients without anterior knee pain. CONCLUSION: In
      the current clinical practice, the appearance of anterior knee pain persists as a
      problem; simply changing to a mobile bearing does not seem to be the solution.
      The posterior stabilized mobile total knee did not sustain the advantage of less
      anterior knee pain, compared with the posterior stabilized fixed total knee
      arthroplasty. LEVEL OF EVIDENCE: Therapeutic study, Level II.

PMID- 23124602
TI  - Anteromedial ridging of the femoral intercondylar notch: an anatomic study of 170
      archival skeletal specimens.
AB  - PURPOSE: (1) To identify the relationship between anteromedial notch ridging, a
      recently identified non-contact anterior cruciate ligament injury risk factor,
      and patient demographics in a general population. (2) To characterize the
      symmetry of the femoral notch between knees. METHODS: The femoral notches of 170
      non-arthritic archival skeletal specimens devoid of soft-tissue attachments (n =
      79 females, 90 males, 34.3 +/- 15.7 years) were measured for notch width, ridge
      thickness, and outlet stenosis due to ridging. Measurements were compared by race
      and sex by ANOVA, and Pearson correlations were calculated for all continuous
      measures. RESULTS: Percent stenosis was associated with increasing age (p <
      0.001, r = 0.40). Ridge thickness was similar among men (2.7 +/- 1.6 mm) and
      women (3.1 +/- 1.5; n.s.). Women had narrower notches (16.0 +/- 2.1 mm) and
      higher percent stenosis (19.6 +/- 9.9 %) than men (p <= 0.001; men 19.3 +/- 2.4
      mm; 14.4 +/- 8.7 %). African American men have narrower notches than Caucasian
      men (20.4 +/- 2.5 vs. 18.7 +/- 2.3 mm, respectively; p = 0.002) with no
      difference between women of both races (16.2 +/- 2.5 vs. 15.8 +/- 1.6 mm,
      respectively; n.s.). A positive association was observed between height and notch
      width among men only (18+ years men p = 0.004, r = 0.33; women n.s., r = 0.21).
      Finally, both total notch width and ridge thickness are symmetric between knees
      (p < 0.001; r = 0.98 and 0.93, respectively). CONCLUSIONS: Women have narrower
      femoral notches overall and also exhibit greater percent notch stenosis due to
      anteromedial ridging than men. Anteromedial ridging increases with age,
      suggesting progressive formation over time. Finally, both notch width and ridge
      thickness are highly symmetric between knees.

PMID- 23124603
TI  - The relationship between transient elastography and histological collagen
      proportionate area for assessing fibrosis in chronic viral hepatitis.
AB  - BACKGROUND: Collagen proportionate area (CPA) has a better correlation with
      hepatic venous pressure gradient (HVPG) than with Ishak stage. Liver stiffness
      measurement (LSM) is proposed as non invasive marker of portal
      hypertension/disease progression. Our aim was to compare LSM and CPA with Ishak
      staging in chronic viral hepatitis, and HVPG in HCV hepatitis after
      transplantation. METHODS: One hundred and sixty-nine consecutive patients with
      chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections pre/post
      liver transplantation (LT), had a liver biopsy combined with LSM (transient
      elastography), CPA (biopsies stained with Sirius Red and evaluated by digital
      image analysis and expressed as CPA) and HVPG (measured contemporaneously with
      transjugular biopsies in LT HCV patients). RESULTS: LSM was dependent on CPA in
      HBV (r (2) = 0.61, p < 0.0001), HCV (r (2) = 0.59, p < 0.0001) and LT groups (r
      (2) = 0.64, p < 0.0001). In all three groups, CPA and Ishak were predictors of
      LSM, but multivariately CPA was better related to LSM (HBV: r (2) = 0.61, p <
      0.0001; HCV: r (2) = 0.59, p < 0.0001; post-LT: r (2) = 0.68, p < 0.0001) than
      Ishak stage. In the LT group, multiple regression analysis including HVPG, LSM,
      aspartate aminotransferase to platelet ratio index (APRI) and Ishak stage/grade,
      showed that only CPA was related to HVPG (r (2) = 0.41, p = 0.01), both for HVPG
      >=6 mmHg (OR 1.34, 95 % CI 1.14-1.58; p < 0.0001) or >=10 mmHg (OR 1.25, 95 % CI
      1.06-1.47; p = 0.007). CONCLUSION: CPA was related to LSM in HBV or HCV hepatitis
      pre/post-LT. CPA was better related to LSM than Ishak stage. In the LT HCV group,
      CPA was better related to HVPG than Ishak stage/grade, LSM or APRI. CPA may
      represent a better comparative histological index for LSM, rather than
      histological stages.

PMID- 23124605
TI  - Src and fibroblast growth factor 2 independently regulate signaling and gene
      expression induced by experimental injury to intact articular cartilage.
AB  - OBJECTIVE: To investigate whether cartilage injury activates protein tyrosine
      kinases distinct from fibroblast growth factor (FGF)-related signaling, and
      whether they contribute to injury-induced gene responses. METHODS: Phosphokinases
      and protein tyrosine phosphorylation were assayed by Western blotting of
      cartilage lysates. Immunoprecipitation and Western blotting with 4G10 antibody
      and immunoprecipitation kinase assay were carried out. Tyrosine-phosphorylated
      proteins on silver-stained gels of injured cartilage lysates were identified by
      mass spectrometry. Messenger RNA induction in cartilage explants was assessed by
      quantitative reverse transcriptase-polymerase chain reaction. RESULTS: Protein
      tyrosine phosphorylation occurred within seconds of injury to the surface of
      intact articular cartilage, as did activation of MAPKs and IKK. Activation did
      not reoccur upon reinjury of cultured explants. The prominent tyrosine
      phosphorylated proteins focal adhesion kinase, paxillin, and cortactin were
      identified as substrates of Src family kinases. The Src family kinase inhibitor
      PP2 blocked injury-induced tyrosine phosphorylation. It did not prevent
      activation of the MAPKs and IKK but differentially inhibited 8 of 10 inflammatory
      response genes that were induced by injury. In contrast, FGF signaling blockade
      with PD173074 reduced all MAPK and IKK activation by ~50% and inhibited a
      different subset of genes but had no effect on Src-like signaling. CONCLUSION:
      Injury to the surface of intact articular cartilage activates Src-like kinases as
      well as MAPKs and IKK (implying NF-kappaB activation). FGF-2 contributes to
      MAPK/IKK activation but not to Src-like signaling, suggesting that the latter is
      a parallel pathway that also regulates the injury-induced inflammatory gene
      response.

PMID- 23124607
TI  - Relationships among identity, perceived discrimination, and depressive symptoms
      in eight ethnic-generational groups.
AB  - OBJECTIVE: Examine whether personal identity confusion and ethnic identity,
      respectively, moderate and/or mediate the relationship between perceived
      discrimination (PD) and depressive symptoms (DS) in eight ethnic-generational
      groups. METHOD: The sample consisted of 9665 students (73% women; mean age 20.31)
      from 30 colleges and universities from around the United States. Cross-sectional
      data were gathered through a confidential online survey. RESULTS: Across groups,
      PD and ethnic identity levels varied, while identity confusion levels were mostly
      similar. Neither identity confusion nor ethnic identity moderated the PD-DS
      relationship for any groups. However, identity confusion was a partial mediator
      for immigrant and nonimmigrant Hispanic/Latino(a) and White/European American
      participants. Identity confusion also suppressed the PD-DS relationship for
      Black/African American participants. CONCLUSIONS: Results highlight the need for
      additional research on identity confusion's role in the PD-distress link and the
      importance of addressing ethnicity and generation status when examining the
      effects of PD on college students' mental health.

PMID- 23124604
TI  - Sexual function and patients' perceptions in inflammatory bowel disease: a case
      control survey.
AB  - BACKGROUND: Sexuality is important when assessing quality of life (QoL), which is
      often disturbed in inflammatory bowel disease (IBD). However, sexuality is not
      addressed in most QoL questionnaires. AIMS: To evaluate the prevalence and
      predisposing factors of sexual dysfunction among IBD patients, and their own
      perception. METHODS: A postal survey was conducted in IBD patients 25-65 years of
      age from two tertiary centres. Patients were asked to provide a control of the
      same gender and age without IBD. The questionnaire assessed patient perception of
      the impact of IBD on their sexuality, and also allowed calculation of the
      Erectile Function International Index or the Female Sexual Function Index.
      RESULTS: A total of 355 patients and 200 controls were available for the final
      analysis. Both groups were comparable except for a higher proportion of
      individuals who had been treated for depression among patients. Half of the
      female and one-third of the male patients considered that both sexual desire and
      satisfaction worsened after IBD diagnosis. As compared to controls, both men and
      women with IBD showed significantly lower scores in sexual function indexes, but
      a higher prevalence of sexual dysfunction was only noticed among women.
      Independent predictors of sexual dysfunction among IBD patients were the use of
      corticosteroids in women, and the use of biological agents, depression and
      diabetes in men. CONCLUSIONS: Sexuality is often disturbed in IBD patients,
      particularly among women. Many factors seem to contribute to worsened intimacy.
      Sexuality should be considered when QoL is assessed in these patients.

PMID- 23124608
TI  - A comparison of subchondral bone mineralization between the glenoid cavity and
      the humeral head on 57 cadaverous shoulder joints.
AB  - PURPOSE: Mineralization distribution of the subchondral bone plate can be used as
      a marker for long-term stress distribution in diarthrodial joints. Severe
      injuries or pathological changes of the glenohumeral joint often end in
      osteoarthritis, where shoulder arthroplasty has become the treatment of choice.
      The computed tomography osteoabsorptiometry (CT-OAM) is a non-invasive method to
      determine the distribution of the mineralization of the subchondral bone plate in
      vivo, which is an important factor concerning the implantation of orthopedic
      endoprostheses. The aim of this study was to investigate the mineralization of
      both joint partners of the glenohumeral joint and to compare them with each
      other. METHODS: The distribution of the mineralization of the subchondral bone
      plate of 57 shoulder specimens was determined by means of CT-OAM. To evaluate a
      correlation between age and localization of subchondral mineralization maxima,
      the Chi-square test correlation test was applied. RESULTS: Forty-nine glenoid
      cavities (86 %) showed a bicentric mineralization distribution pattern with
      anterior and posterior maxima, only 8 glenoid cavities (14 %) revealed a
      monocentric mineralization pattern with anterior maxima. Forty-five humeral heads
      (79 %) showed a bicentric distribution pattern with anterior and posterior
      maxima, 12 humeral heads (21 %) could be classified as monocentric with a centro
      posterior pronounced maximum. CONCLUSIONS: We could demonstrate that stress
      distribution in both joint partners of the glenohumeral joint is inhomogeneous
      and characteristically bicentric due to the physiological incongruity.
      Monocentric mineralization patterns can result as a cause of age-related loss of
      incongruity.

PMID- 23124609
TI  - Difference in subchondral cancellous bone between postmenopausal women with hip
      osteoarthritis and osteoporotic fracture: implication for fatigue microdamage,
      bone microarchitecture, and biomechanical properties.
AB  - OBJECTIVE: Osteoarthritis (OA) and osteoporosis (OP) of the hip rarely occur in
      the same patient. The purpose of this study was to determine whether this
      difference might be attributable to the different quantity and quality of
      subchondral cancellous bone in the two conditions. METHODS: Subchondral
      cancellous bone from the femoral head was obtained at the time of hip
      arthroplasty from 60 postmenopausal women, 30 with OA and 30 with OP. In each
      group, 10 specimens were subjected to compressive fatigue loading and 20 were
      left nonloaded. Specimens were examined by compressive mechanical testing, micro
      computed tomography scanning, fluorescence microscopy, and nanoindentation
      techniques. RESULTS: Both the ultimate stress and the elastic modulus of
      cancellous bone from OA patients were significantly higher than those of
      cancellous bone from OP patients (P < 0.05). Compared to cancellous bone from OP
      patients, the bone volume fraction and trabecular thickness were significantly
      increased, but bone matrix mineralization was significantly decreased, in
      cancellous bone from OA patients (P < 0.05 for each comparison). The microcrack
      density was significantly higher in OP cancellous bone than in OA cancellous bone
      (P < 0.001), irrespective of fatigue loading. In addition, fatigue loading
      resulted in a significant increase in microcrack density in both OA and OP
      cancellous bone (P < 0.001). There was no significant difference in
      nanoindentation elastic modulus and hardness between cancellous bone from OA and
      OP patients, as well as between bones with and without fatigue loading.
      CONCLUSION: The difference in mechanical properties between OA and OP cancellous
      bone is attributed to different bone mass and bone structure. OP cancellous bone
      is susceptible to fatigue damage due to insufficient structure. However,
      increased bone volume and plate-like structure provide OA cancellous bone a
      superior capacity to resist fatigue damage.

PMID- 23124612
TI  - BOLD signal in memory paradigms in hippocampal region depends on echo time.
AB  - PURPOSE: To evaluate the hypothesis that the entire hippocampus might be affected
      by susceptibility artifacts. Previous studies described susceptibility artifacts
      in the amygdala and the anterior hippocampus. MATERIALS AND METHODS: We
      investigated 20 subjects with a verbal memory paradigm aiming at testing two
      different TEs (45 vs. 64 msec) at 1.5 T for hippocampal blood oxygenation level
      dependent (BOLD) activity. T2* maps were calculated from the normalized mean echo
      planar imaging (EPI) of the two echo times (TEs). RESULTS: Within the hippocampal
      region of interest (ROI), the amount of suprathreshold voxels was significantly
      higher at TE = 64 msec compared to TE = 45 msec. When corrected for multiple
      comparisons (family-wise error [FWE] in a small volume of interest, P < 0.05) we
      no longer found significant activations at TE = 45 msec, while a significant
      number of voxels remained after the small volume correction (P < 0.05, FWE)
      within the ROI at TE = 64 msec. CONCLUSION: Although a shorter TE demonstrates
      advantages, a TE of 45 msec leads to a significant loss of BOLD signal detection
      in memory functional magnetic resonance imaging (fMRI) studies when compared to
      64 msec. We assume that the hippocampal region, even the anterior part, is not
      strongly affected by susceptibility gradients.

PMID- 23124613
TI  - Downregulation of LRIG1 expression by RNA interference promotes the aggressive
      properties of glioma cells via EGFR/Akt/c-Myc activation.
AB  - The LRIG1 [leucine-rich repeats and immunoglobulin-like domains (LRIG)] gene is
      not universally downregulated in human cancers, and its role in tumorigenesis and
      the development of glioma has not been well addressed. In this study, we used
      short hairpin RNA (shRNA)-triggered RNA interference (RNAi) to block LRIG1 gene
      expression in the GL15 human glioma cell line. Specific downregulation of LRIG1
      by shRNA resulted in significantly enhanced capabilities of proliferation,
      inhibition of apoptosis and invasion in the GL15 cells. LRIG1 repression induced
      marked activation of epidermal growth factor receptor (EGFR), protein kinase B
      (Akt) and c-Myc signaling molecules. Our results demonstrated that RNAi against
      LRIG1 may effectively downregulate LRIG1 gene expression. LRIG1 functions as a
      tumor suppressor in the pathogenesis of glioma via EGFR/Akt/c-Myc activation.

PMID- 23124614
TI  - The professional medical ethics model of decision making under conditions of
      clinical uncertainty.
AB  - The professional medical ethics model of decision making may be applied to
      decisions clinicians and patients make under the conditions of clinical
      uncertainty that exist when evidence is low or very low. This model uses the
      ethical concepts of medicine as a profession, the professional virtues of
      integrity and candor and the patient's virtue of prudence, the moral management
      of medical uncertainty, and trial of intervention. These features combine to
      justifiably constrain clinicians' and patients' autonomy with the goal of
      preventing nondeliberative decisions of patients and clinicians. To prevent
      biased recommendations by the clinician that promote such nondeliberative
      decisions, medically reasonable alternatives supported by low or very low
      evidence should be offered but not recommended. The professional medical ethics
      model of decision making aims to improve the quality of decisions by reducing the
      unacceptable variation that can result from nondeliberative decision making by
      patients and clinicians when evidence is low or very low.

PMID- 23124615
TI  - Decision support for patients: values clarification and preference elicitation.
AB  - Providing a patient with decision support involves helping that person to choose
      among two or more elective health care options. "Values Clarification" and
      "Preference Elicitation" are integral to the full decision-support process.
      During values clarification, the patient and clinician gain insight into the
      importance that the patient ascribes to the options' positive and negative
      characteristics. During preference elicitation, the patient identifies which
      options are, overall, personally most favored (and, by corollary, which are least
      favored). This article identifies the roles that values clarification/preference
      elicitation (VC/PE) play in the full process of patients' decision support,
      outlines various approaches to fostering VC/PE, and poses some fundamental and
      applied research questions about VC/PE. It also argues that, in order to proceed
      to answer the posed research questions, investigators in the field of patients'
      decision support require a systematic set of criteria for comparing the
      performance of different VC/PE techniques.

PMID- 23124616
TI  - Supporting shared decisions when clinical evidence is low.
AB  - There is growing interest in shared decision making (SDM) in the United States
      and globally, at both the clinical and policy levels. SDM is typically employed
      during "preference-sensitive" decisions, where there is equipoise between
      treatment options with equal or similar outcomes from a medical standpoint. In
      these situations, patients' preferences for the possible risks, benefits, and
      trade-offs between options are central to the decision. However, SDM also may be
      appropriate in clinical situations besides those in which data demonstrate
      equipoise. In situations of low evidence, where evidence is conflicting,
      unavailable or not applicable to an individual patient, supporting SDM can
      present unique challenges, above and beyond the challenges faced during more
      standard preference-sensitive decisions. This article discusses challenges in
      supporting shared decisions when clinical evidence is low, describes strategies
      that can facilitate SDM despite low evidence, and suggests avenues for future
      research to explore further these proposed strategies.

PMID- 23124617
TI  - Supporting shared decision making when clinical evidence is low.
AB  - Shared decision making (SDM) is the process of providing the patient with
      critical information that can support his or her informed participation in
      decision making. Shared decision making has become accepted as an important
      component of quality health care. Influenced by its foundations in law and ethics
      and by empirical work on its value as a tool to reduce variability in care, a
      perception has developed that SDM is relevant primarily to clinical situations
      with high-quality clinical evidence. This raises the question of the role of SDM
      in situations when clinical evidence is lacking or of low quality. This article
      posits that SDM is equally relevant and important to low-evidence situations in
      four ways--SDM fosters shared acceptance of uncertainty, closes the gap in
      knowledge between patient and physician, promotes patient empowerment, and
      enhances trust through transparent communication.

PMID- 23124618
TI  - Expression of the cysteinyl leukotriene 1 receptor and glucocorticoid receptor
      beta in nasal polyps.
AB  - The objective of this study was to analyze the expression of cysteinyl
      leukotriene 1 (CysLT1) receptor and glucocorticoid receptors (GRs) in nasal
      polyps, and to evaluate the relationship between the expression of CysLT1
      receptors and that of GRs. Nasal polyps were taken from 32 patients of chronic
      rhinosinusitis with nasal polyposis. Samples of middle turbinate from seven
      healthy subjects were used as controls. Specimens were immunohistochemically
      stained for CysLT1 receptor, GR-alpha and GR-beta receptor, and were quantified
      in the unit area of the tissues. Numbers of CysLT1 receptor-positive cells were
      much increased in nasal polyps than in middle turbinate (281 +/- 67 vs. 157 +/-
      85 cells/mm(2), P = .01). There was no significant difference in the numbers of
      GR-alpha positive cells between nasal polyps and normal turbinate mucosa. GR-beta
      positive cells were increased in nasal polyps as compared to normal turbinate
      mucosa (36 +/- 8 vs. 19 +/- 7 cells/mm(2), P = .03). A significant relationship
      was found between the expression of CysLT1 receptor and GR-beta in nasal polyps
      (R = .525, P = .04), whereas there was no significant relationship between the
      expression of CysLT1 receptor and GR-alpha in nasal polyps. Our study shows that
      CysLT1 receptor expression predominates on GR-beta over-expressed polyps. This
      may suggest the additional effect of CysLT1 receptor antagonist for the treatment
      of nasal polyposis resistant to steroid alone.

PMID- 23124619
TI  - Value of laparoscopy before cytoreductive surgery and hyperthermic
      intraperitoneal chemotherapy for peritoneal carcinomatosis.
AB  - BACKGROUND: The outcome of cytoreductive surgery combined with hyperthermic
      intraperitoneal chemotherapy (HIPEC) depends on the extent of peritoneal
      carcinomatosis. The role of laparoscopy in the preoperative assessment of extent
      of peritoneal carcinomatosis in potential candidates for cytoreductive surgery
      and HIPEC was evaluated in a consecutive series. METHODS: Patients with
      peritoneal carcinomatosis from colorectal cancer or appendiceal cancer,
      pseudomyxoma peritonei or peritoneal mesothelioma referred to a single, national
      HIPEC centre were included prospectively between June 2006 and January 2012. From
      September 2010, preoperative evaluation also included a laparoscopy in patients
      deemed amenable to cytoreductive surgery and HIPEC after radiological evaluation,
      apart from those with pseudomyxoma peritonei with massive amounts of mucin.
      RESULTS: In the period before laparoscopic evaluation, 70 patients underwent
      laparotomy of whom 39 (56 per cent) completed cytoreductive surgery and HIPEC.
      After the introduction of laparoscopic assessment, diagnostic laparoscopy was
      planned in 45 patients and successful in 43. The laparoscopic evaluation excluded
      18 patients from surgery because of extensive disease, among other reasons.
      Laparoscopy was uneventful and associated with no deaths. Twenty-seven patients
      were considered amenable to cytoreductive surgery and HIPEC based on laparoscopic
      findings, of whom 17 completed this treatment; the disease was unresectable in
      the remaining ten patients. Of 13 patients who were not eligible for laparoscopic
      evaluation and were subjected to cytoreductive surgery plus HIPEC, 11 completed
      the procedure. The overall completion rate of cytoreductive surgery and HIPEC
      increased to 70 per cent (28 of 40) after the introduction of laparoscopic
      evaluation. CONCLUSION: Diagnostic laparoscopy was valuable in preoperative
      evaluation of the extent of peritoneal carcinomatosis, and improved patient
      selection for cytoreductive surgery and HIPEC.

PMID- 23124620
TI  - Prediction of the stability of imipenem in intravenous mixtures.
AB  - The purpose of this study was to predict the stability of imipenem in a mixed
      infusion. The hydrolysis of imipenem in aqueous solution was found to be
      accelerated by pH, and by increasing concentrations of sodium bisulfite (SBS) and
      L-cysteine. Equations were derived for the degradation rate constants (k(obs)) of
      pH, SBS and L-cysteine and fractional rate constants were estimated by nonlinear
      least-squares method (quasi-Newton method using the solver in Microsoft Excel) at
      25 degrees C. The activation energy (Ea) and frequency factor (A) were calculated
      using the Arrhenius equation. The pH of the mixed infusion was estimated using
      the pH characteristic (PHC) curve. From these results, an equation was derived
      giving the residual ratio (%) of imipenem at any time after mixing an infusion
      containing SBS and/or L-cysteine at any temperature and at pH 4.0-10.0. A high
      correlation was shown to exist between the estimated and determined residual
      ratios (%).

PMID- 23124621
TI  - Bending rigid molecular rods: formation of oligoproline macrocycles.
AB  - Bent but not broken: cyclic oligoprolines are accessed in a reaction that
      effectively bends rigid oligoproline peptides (see scheme; TBDMS=tert
      butyldimethylsilyl). The stitching is accomplished during macrocyclization
      enabled by aziridine aldehydes and isocyanides. Molecular modeling studies
      suggest that electrostatic attraction between the termini of the linear peptide
      is pivotal for macrocyclization. The macrocycles were studied by circular
      dichroism with a polyproline II structure being observed in larger macrocycles.

PMID- 23124622
TI  - Progression of cortical thinning in early Parkinson's disease.
AB  - The aim of this study was to investigate the progression of cortical thinning and
      gray-matter (GM) volume loss in early Parkinson's disease (PD). MRI and
      neuropsychological assessment were obtained at baseline and follow-up (mean +/-
      standard deviation = 35.50 +/- 1.88 months) in a group of 16 early-PD patients (H
      & Y stage <=II and disease duration <=5 years) and 15 healthy controls matched
      for age, gender, and years of education. FreeSurfer software was used for the
      analysis of cortical thickness as well as for cortical and subcortical volumetric
      analyses. Voxel-based morphometry analysis was performed using SPM8. Compared to
      controls, PD patients showed greater regional cortical thinning in bilateral
      frontotemporal regions as well as greater over-time total GM loss and amygdalar
      volume reduction. PD patients and controls presented similar over-time changes in
      cognitive functioning. In early-PD patients, global GM loss, amygdalar atrophy,
      and cortical thinning in frontotemporal regions are specifically associated with
      the PD-degenerative process.

PMID- 23124624
TI  - Diabetes mellitus and risk of prostate cancer: an updated meta-analysis based on
      12 case-control and 25 cohort studies.
AB  - The association between diabetes and risk of prostate cancer has been
      investigated widely. However, study results remain inconsistent and
      contradictory. Using a meta-analytic approach, the present study explore the
      relationship incorporating more recent studies and provide more powerful evidence
      without the limitations of any individual study. Relevant studies were identified
      by searching Pubmed and the Cochrane Central Register of Controlled Trials
      through May 18, 2012. The strength of the relationship between diabetes mellitus
      and risk of prostate cancer was assessed using relative risk (RR). Either a fixed
      effects or random effects model was used to calculate the pooled RRs.
      Stratification analyses and sensitivity analyses were conducted, and publication
      bias was assessed by Egger's test and Begg's test. Twelve case-control studies
      involving 9,767 cases and 19,790 controls, and 25 cohort studies involving
      118,825 cases were included. The person-years of follow-up ranged from 29,963 to
      6,264,890 among included cohort studies. Diabetes was not significantly
      associated with incidence of prostate cancer in our analysis of case-control
      studies only (RR = 0.846, 95 % CI [0.710, 1.009]) or that of cohort studies only
      (RR = 0.925, 95 % CI [0.811, 1.054]). However, through subgroup analyses,
      statistically significant associations between diabetes and prostate cancer were
      found when considering population-based studies only (RR = 0.719, 95 % CI [0.637,
      0.812]), cohort studies conducted in the United States (RR = 0.789, 95 % CI
      [0.727, 0.857]), and studies with follow-up of more than 5 years. Compared to
      risk of prostate cancer among people without diabetes, diabetic patients using
      insulin treatment experienced reduced incidence of prostate cancer in both case
      control and cohort studies. The results suggest that diabetes mellitus is
      associated with decreased incidence of prostate cancer, specifically in the
      population of the United States. In addition, the time since onset of diabetes
      was positively associated with decreasing incidence of prostate cancer. The
      present conclusions should be considered carefully, however, and confirmed with
      further studies.

PMID- 23124623
TI  - Age-related effect of serotonin transporter genotype on amygdala and prefrontal
      cortex function in adolescence.
AB  - The S and LG alleles of the serotonin transporter-linked polymorphic region (5
      HTTLPR) lower serotonin transporter expression. These low-expressing alleles are
      linked to increased risk for depression and brain activation patterns found in
      depression (increased amygdala activation and decreased amygdala-prefrontal
      cortex connectivity). Paradoxically, serotonin transporter blockade relieves
      depression symptoms. Rodent models suggest that decreased serotonin transporter
      in early life produces depression that emerges in adolescence, whereas decreased
      serotonin transporter that occurs later in development ameliorates depression.
      However, no brain imaging research has yet investigated the moderating influence
      of human development on the link between 5-HTTLPR and effect-related brain
      function. We investigated the age-related effect of 5-HTTLPR on amygdala
      activation and amygdala-prefrontal cortex connectivity using a well-replicated
      probe, an emotional face task, in children and adolescents aged 9-19 years. A
      significant genotype-by-age interaction predicted amygdala activation, such that
      the low-expressing genotype (S/S and S/LG ) group showed a greater increase in
      amygdala activation with age compared to the higher expressing (LA /LA and S/LA )
      group. Additionally, compared to the higher expressing group, the low-expressing
      genotype group exhibited decreased connectivity between the right amygdala and
      ventromedial prefrontal cortex with age. Findings indicate that low-expressing
      genotypes may not result in the corticolimbic profile associated with depression
      risk until later adolescence.

PMID- 23124625
TI  - The lysine48-based polyubiquitin chain proteasomal signal: not a single child
      anymore.
AB  - The conjugation of ubiquitin (Ub) to proteins is involved in the regulation of
      many processes. The modification serves as a recognition element in trans, in
      which downstream effectors bind to the modified protein and determine its fate
      and/or function. A polyUb chain that is linked through internal lysine (Lys)-48
      of Ub and anchored to an internal Lys residue of the substrate has become the
      accepted "canonical" signal for proteasomal targeting and degradation. However,
      recent studies show that the signal is far more diverse and that chains based on
      other internal linkages, as well as linear or heterologous chains made of Ub and
      Ub-like proteins and even monoUb, are recognized by the proteasome. In addition,
      chains linked to residues other than internal Lys were described, all challenging
      the current paradigm.

PMID- 23124626
TI  - Effect of metformin treatment on endometrial vascular indices in anovulatory
      obese/overweight women with polycystic ovarian syndrome using three-dimensional
      power doppler ultrasonography.
AB  - PURPOSE: Metformin has been shown to be an effective treatment for anovulatory
      polycystic ovary syndrome (PCOS) patients in terms of menstrual cyclicity,
      ovulation, and pregnancy, as well as reduction of early miscarriage rate. The aim
      of the study is to assess the effect of metformin on the endometrial vascular
      indices in anovulatory obese PCOS women using three-dimensional power Doppler
      sonography (3DPDUS). METHODS: A prospective study was set to determine the
      beneficial effects of metformin on PCOS patients. Fifty anovulatory obese PCOS
      patients were compared with another 50 healthy volunteers who were age- and body
      mass index-matched (control group). PCOS patients were treated with metformin
      (Glucophage; MerckSerono) 850 mg 3 times a day for 6 months. Assessment of the
      endometrial thickness and volume, uterine Doppler indices, and Doppler vascular
      indices of the endometrium and subendometrium in the periovulatory and midluteal
      phases were performed with 3DPDUS. RESULTS: There was a significant increase in
      the endometrial thickness, endometrial volume, and endometrial and subendometrial
      vascularity indices (vascularization index, flow index, vascularization flow
      index) after 6 months of metformin treatment in PCOS women, whereas there was no
      change in the resistance index and the pulsatility index of the uterine artery in
      both periovulatory and midluteal phases. CONCLUSIONS: Metformin, owing to its
      metabolic, endocrine, vascular, and anti-inflammatory effects, improves markers
      of endometrial receptivity.

PMID- 23124627
TI  - Has the arthroscopically assisted reduction of acute AC joint separations with
      the double tight-rope technique advantages over the clavicular hook plate
      fixation?
AB  - PURPOSE: The purpose of this study was to compare the results after
      arthroscopically assisted double TightRope((r))-(TR) reduction with results after
      clavicular hook plate (HP) fixation in acute high-grade acromioclavicular (AC)
      joint separations. METHODS: Between 2004 and 2010, 69 consecutive patients with
      acute AC joint separations type Rockwood III and V were subjected to surgical
      reconstruction. 56 patients (81 %) were available for evaluation. Thereof, 30
      (median age: 39 years; n = 12 acute Rockwood III and n = 18 Rockwood V injuries)
      were treated by a clavicular HP and 26 (median age: 39 years; n = 10 acute
      Rockwood III and n = 16 Rockwood V injuries) using the double TR technique. Group
      HP was evaluated at a median of 48 (7-77) months after surgery and the TR group
      17 (7-29) months after stabilization. Visual Analogue Scale (VAS) for Pain,
      Simple Shoulder Test (SST), Constant Score (CS) and Taft Score (TS) were
      assessed. Sonographic measurements were performed to evaluate recurrent
      instability. RESULTS: Clinical examination demonstrated comparable results
      without significant differences. In the groups HP and TR, the VAS was median 0.8
      (range, 0.0-7.5) and 0.4 (range, 0.0-5.7), the SST reached median 11 (range, 0-12
      points) and 12 points (range, 8-12 points). The CS was median 92.4 % (range, 21.5
      105.4 %) and 94.0 % (range, 54.6-105.3 %) and the TS median 10 (range, 3-12
      points) and 10 points (range, 5-12 points). Sonographic measurements showed a
      mean coracoclavicular (CC) distance of 25.3 +/- 4.5 (HP) and 25.5 +/- 4.3 mm (TR)
      (n.s.). In both groups, CC distance of the operated side was significantly higher
      compared to the uninjured side. The complication rate was 13 % in group HP and 12
      % in group TR. CONCLUSIONS: In acute high-grade AC joint instabilities, both
      techniques lead to mostly good and excellent clinical results, although
      comparable partial recurrent vertical instability could be observed. Diagnosis
      and therapy of concomitant glenohumeral injuries and no obligatory implant
      removal are advantages of the arthroscopic procedure.

PMID- 23124629
TI  - Anatomical and electrophysiological mechanisms for asymmetrical excitatory
      propagation in the rat insular cortex: in vivo optical imaging and whole-cell
      patch-clamp studies.
AB  - The insular cortex (IC) integrates limbic information from the amygdala and
      hypothalamic nucleus to multimodal sensory inputs, including visceral, gustatory,
      and somatosensory information. However, the functional framework of excitation in
      the IC is still unknown. We performed optical imaging and single pyramidal
      neuronal staining using a whole-cell patch-clamp technique in urethane
      anesthetized rats to elucidate the precise anatomical and physiological features
      of IC pyramidal neurons, which regulate cortical information processing via their
      horizontal connections. Optical imaging revealed that electrical stimulation of
      the granular (GI) or dysgranular (DI) IC elicited characteristic excitatory
      propagations along the rostrocaudal axis parallel to the rhinal fissure, with a
      preference toward the rostral direction. Spatial patterns of the dendrites and
      axons of layer II/III pyramidal cells in the DI/GI support these functional
      features of excitation; for example, rostrocaudal axonal arbors tend to extend
      with a rostral directional preference. The mean length of the axons from the soma
      to the farthest site rostrally was ~50% longer than that of the caudal length.
      Pyramidal cells in the DI/GI exhibited spontaneous membrane oscillation in the UP
      and DOWN states. Similarly to the evoked signals obtained by optical imaging,
      repetitive electrical stimulation of the caudal IC ~1 mm away from the recorded
      cells (five pulses at 50 Hz) induced the summation of evoked excitatory
      postsynaptic potentials during the DOWN state and profound inhibitory
      postsynaptic potentials during the UP state. Clarification of the excitation
      feature with its cellular basis provides new clues about the functional
      mechanisms of the asymmetric propagation of neural activities in the IC.

PMID- 23124628
TI  - Patella instability: building bridges across the ocean a historic review.
AB  - The diagnosis of and treatment for musculoskeletal disease and injuries have seen
      an explosion of new knowledge. More precise imaging, correlative injury anatomy,
      more focused physical examination features, among others, have led this upsurge
      of current insight. Crucial to this knowledge revolution is the expansion of
      international knowledge, which is aided by an adoption of a universal scientific
      language, electronic transfer of information, and personal communication of
      surgeons and scientists across national boundaries. One area where this is
      particularly evident is in our knowledge and treatment for patellofemoral
      disorders. This article will review the developments in the management of
      patellar dislocations by tracing their historical roots. This is not meant to be
      a comprehensive review, but rather to give current readers a "historical memory"
      upon which to judge and interpret our present-day bridge of knowledge. Level of
      evidence V.

PMID- 23124630
TI  - Quantitative imaging of murine osteoarthritic cartilage by phase-contrast micro
      computed tomography.
AB  - OBJECTIVE: The mouse is an optimal model organism in which gene-environment
      interactions can be used to study the pathogenesis of osteoarthritis (OA). The
      gold standard for arthritis research in mice is based on histopathology and
      immunohistochemistry, which are labor-intensive, prone to sampling bias and
      technical variability, and limited in throughput. The aim of this study was to
      develop a new technique that assesses mouse cartilage by integrating quantitative
      volumetric imaging techniques. METHODS: A novel mouse model of OA was generated
      by cruciate ligament transection (CLT) and evaluated by histopathology and
      immunohistochemistry. Knee joint specimens were then imaged using a new technique
      that combines high-resolution micro-computed tomography (micro-CT) and phase
      contrast optics followed by quantitative analyses. A comparative analysis was
      also performed in a previously established mouse model of OA generated by
      destabilization of the medial meniscus (DMM). RESULTS: Phase-contrast micro-CT
      achieved cellular resolution of chondrocytes and quantitative assessment of
      parameters such as articular cartilage volume and surface area. In mouse models
      of OA generated by either CLT or DMM, we showed that phase-contrast micro-CT
      distinguished control and OA cartilage by providing quantitative measures with
      high reproducibility and minimal variability. Features of OA at the cellular or
      tissue level could also be observed in images generated by phase-contrast micro
      CT. CONCLUSION: We established an imaging technology that comprehensively
      assessed and quantified the 2-dimensional and 3-dimensional changes of articular
      cartilage. Application of this technology will facilitate the rapid and high
      throughput assessment of genetic and therapeutic models of OA in mice.

PMID- 23124631
TI  - A pilot study of health priorities of Somalis living in Kansas City: laying the
      groundwork for CBPR.
AB  - African immigrant and refugee communities remain medically underserved in the
      United States. Formative efforts are being directed to address the local needs of
      communities by researchers, community agencies, and local populations. However,
      there is a paucity of data and sparse documentation regarding these efforts. The
      objectives for this pilot study were to identify the health priorities of the
      Kansas City Somali community and to establish a working relationship between an
      academic medical university and the local Somali community. Our team used
      community-based participatory research principles and interviewed Somali
      community members (n = 11). Participants stated that chronic and mental health
      conditions were of primary concern. Medical system navigation and literacy
      struggles were identified as barriers. Participants offered possible solutions to
      some health issues, e.g., using community health workers and Qur'anic readers.
      Preliminary findings will help guide future research and inform strategies to
      improve the health and well-being of this community.

PMID- 23124632
TI  - A comparison of health access between permanent residents, undocumented
      immigrants and refugee claimants in Toronto, Canada.
AB  - Understanding the immigrant experience accessing healthcare is essential to
      improving their health. This qualitative study reports on experiences seeking
      healthcare for three groups of immigrants in Toronto, Canada: permanent
      residents, refugee claimants and undocumented immigrants. Undocumented immigrants
      who are on the Canadian Border Services Agency deportation list are understudied
      in Canada due to their precarious status. This study will examine the
      vulnerabilities of this particular subcategory of immigrant and contrast their
      experiences seeking healthcare with refugee claimants and permanent residents.
      Twenty-one semi-structured, one-on-one qualitative interviews were conducted with
      immigrants to identify barriers and facilitators to accessing healthcare. The
      open structure of the interviews enabled the participants to share their
      experiences seeking healthcare and other factors that were an integral part of
      their health. This study utilized a community-based participatory research
      framework. The study identifies seven sections of results. Among them,
      immigration status was the single most important factor affecting both an
      individual's ability to seek out healthcare and her experiences when trying to
      access healthcare. The healthcare seeking behaviour of undocumented immigrants
      was radically distinct from refugee claimants or immigrants with permanent
      resident status, with undocumented immigrants being at a greater disadvantage
      than permanent residents and refugee claimants. Language barriers are also noted
      as an impediment to healthcare access. An individual's immigration status further
      complicates their ability to establish relationships with family doctors, access
      prescriptions and medications and seek out emergency room care. Fear of
      authorities and the complications caused by the above factors can lead to the
      most disadvantaged to seek out informal or black market sources of healthcare.
      This study reaffirmed previous findings that fear of deportation forestalls
      undocumented immigrants from seeking out healthcare through standard means. The
      findings bring to light issues not discussed in great depth in the current
      literature on immigrant health access, the foremost being the immigration status
      of an individual is a major factor affecting that person's ability to seek, and
      experience of, healthcare services. Further, that undocumented immigrants have
      difficulty gaining access to pharmaceuticals and so may employ unregulated means
      to obtain medication, often with the assistance of a doctor. Also, there exists
      two streams of healthcare access for undocumented immigrants--from conventional
      healthcare facilities but also from informal systems delivered mainly through
      community-based organizations. Finally, within the umbrella term 'immigrant'
      there appears to be drastically different healthcare utilization patterns and
      attitudes toward seeking out healthcare between the three subgroups of immigrants
      addressed by this study.

PMID- 23124633
TI  - hMSCs possess the potential to differentiate into DP cells in vivo and in vitro.
AB  - DP (dermal papilla) is a mesenchyme-derived structure situated at the base of the
      HF (hair follicle) that plays an important role in embryonic hair morphogenesis
      and maintenance of the hair growth cycle. hMSCs (human mesenchymal stem cells)
      have gained widespread attention in the field of tissue engineering, but not much
      is known about the differentiation of hMSCs into DP cells. hMSCs involved in HF
      formation were examined in our previous study. Here, we have explored the
      differentiation potential of hMSCs into DP cells by co-culturing hMSCs with DP
      cells, which proved to be the case. During the differentiation process, the
      expression of versican, CD133, SCF (stem cell factor), ET-1 (endothelin-1) and
      bFGF (basic fibroblast growth factor) increased. Compared with hMSCs alone, the
      aggregate number clearly increased when co-cultured with DP cells. The expression
      in vivo of HLA-I (human leucocyte antigen class I) was confined to DP of the
      newly formed HF. The data suggest that hMSCs possess the potential to
      differentiate into DP cells in vivo and in vitro.

PMID- 23124634
TI  - Emergency noninvasive angiography for acute intracerebral hemorrhage.
AB  - Spontaneous ICH is a devastating condition and is associated with significant
      mortality in the acute phase due to ongoing hemorrhage and hematoma expansion. A
      growing body of evidence suggests that there may be considerable utility in
      performing noninvasive vascular imaging during the acute-to-early phase of ICH.
      CTA has become widely available and is sensitive and specific for detecting
      vascular causes of secondary ICH such as aneurysms, arteriovenous malformations,
      dural arteriovenous fistulas, intracranial dissections, and neoplasm. CT
      venography can also diagnose dural sinus thrombosis presenting as hemorrhagic
      infarction. Recent data from stroke populations demonstrate a relatively low risk
      to patients when contrast is administered in the absence of a known serum
      creatinine. Detection of acute contrast extravasation within the hematoma ("spot
      sign") with CT angiography is predictive of subsequent hematoma expansion and is
      associated with increased morbidity and mortality. Risk stratification based on
      acute CTA can inform and expedite decision-making regarding intensive care unit
      admission, blood pressure control, correction of coagulopathy, and neurosurgical
      consultation. Noninvasive vascular imaging should be considered as an important
      component of the initial diagnostic work-up for patients presenting with acute
      ICH.

PMID- 23124635
TI  - Diffusion-weighted MRI: distinction of skull base chordoma from chondrosarcoma.
AB  - BACKGROUND AND PURPOSE: Chordoma and chondrosarcoma of the skull base are rare
      tumors with overlapping presentations and anatomic imaging features but different
      prognoses. We hypothesized that these tumors might be distinguished by using
      diffusion-weighted MR imaging. MATERIALS AND METHODS: We retrospectively reviewed
      19 patients with pathologically confirmed chordoma or chondrosarcoma who
      underwent both conventional and diffusion-weighted MR imaging. Differences in
      distributions of ADC were assessed by the Kruskal-Wallis test. Associations
      between histopathologic diagnosis and conventional MR imaging features (T2 signal
      intensity, contrast enhancement, and tumor location) were assessed with the
      Fisher exact test. RESULTS: Chondrosarcoma was associated with the highest mean
      ADC value (2051 +/- 261 * 10(-6) mm(2)/s) and was significantly different from
      classic chordoma (1474 +/- 117 * 10(-6) mm(2)/s) and poorly differentiated
      chordoma (875 +/- 100 * 10(-6) mm(2)/s) (P < .001). Poorly differentiated
      chordoma was characterized by low T2 signal intensity (P = .001), but other
      conventional MR imaging features of enhancement and/or lesion location did not
      reliably distinguish these tumor types. CONCLUSIONS: Diffusion-weighted MR
      imaging may be useful in assessing clival tumors, particularly in differentiating
      chordoma from chondrosarcoma. A prospective study of a larger cohort will be
      required to determine the value of ADC in predicting histopathologic diagnosis.

PMID- 23124636
TI  - Prevalence and topography of small hypointense foci suggesting microbleeds on 3T
      susceptibility-weighted imaging in various types of dementia.
AB  - BACKGROUND AND PURPOSE: The prevalence and topography of small hypointense foci
      suggesting microbleeds on 3T SWI in various types of dementia have not been
      systematically investigated. The purpose of this study was to determine the
      prevalence and topography of SHF on 3T SWI in patients with different dementia
      subtypes. MATERIALS AND METHODS: We included 347 consecutive patients (217 women,
      130 men; age range, 42-93 years; mean age, 74 years) who attended our memory
      clinic and underwent 3T SWI. They were divided into 6 groups: subjective
      complaints, MCI, AD, DLB, VaD, and FTLD. Two neuroradiologists evaluated the
      number and location of SHF on SWIs. Statistical analyses were performed to
      evaluate inter- and intragroup differences. RESULTS: Of the 347 patients, 160
      (46.1%) exhibited at least 1 small hypointense focus. This was true in 86% with
      VaD, 54% with DLB, 48% with AD, 41% with MCI, 27% with FTLD, and 22% with
      subjective complaints. With the subjective complaints group as a reference, the
      odds ratio adjusted by age, sex, and arterial hypertension was 9.2 (95% CI, 2.0
      43.6) for VaD; 5.4 (95% CI, 1.2-24.3) for AD; 3.1 for DLB (95% CI, 1.1-8.8); 2.0
      for MCI (95% CI, 0.5-8.1); and 1.5 for FTLD (95% CI, 0.4-5.4). There was a
      significant lobar predilection for AD, DLB, and FTLD groups (P < .05).
      CONCLUSIONS: On 3T SWI, patients with VaD, AD, and DLB manifested a high SHF
      prevalence. In patients with AD, DLB, and FTLD, the SHF exhibited a lobar
      predilection.

PMID- 23124637
TI  - Age-related trends in the treatment and outcomes of ruptured cerebral aneurysms:
      a study of the nationwide inpatient sample 2001-2009.
AB  - BACKGROUND AND PURPOSE: Patient age substantially influences treatment decisions
      for ruptured cerebral aneurysms. It would be useful to understand national age
      related trends of treatment techniques and outcomes in patients treated for
      ruptured cerebral aneurysm in the United States. MATERIALS AND METHODS: Using the
      US Nationwide Inpatient Sample, we evaluated trends in treatment technique
      (clipping versus coiling) and discharge status of patients undergoing clipping or
      coiling of ruptured cerebral aneurysms between 2001 and 2009. Outcomes were
      evaluated in relation to 4 age strata: 1) younger than 50 years of age, 2) 50-64
      years of age, 3) 65-79 years of age, and 4) patients 80 years or older. We
      compared outcomes between treatment groups for patients treated between 2001-2004
      with those treated between 2005-2009. RESULTS: A significant increase in the
      proportion of patients undergoing endovascular coiling between 2001 and 2009 was
      noted for all age groups (P < .0001). For both clipped and coiled patients,
      mortality and the proportion of patients discharged to long-term facilities
      increased with age. Overall mortality for patients clipped and coiled decreased
      modestly for all age groups, and overall proportions of patients discharged home
      increased modestly (P < .01) for all age groups except those older than 80 years
      of age. CONCLUSIONS: Between 2001 and 2009, there has been a significant increase
      in the proportion of patients with ruptured aneurysms undergoing endovascular
      coiling rather than aneurysm clipping. This increase was more pronounced in older
      patients. Mortality from aneurysmal subarachnoid hemorrhage decreased during the
      past decade, regardless of aneurysm treatment technique.

PMID- 23124638
TI  - Diagnostic accuracy of PET for recurrent glioma diagnosis: a meta-analysis.
AB  - BACKGROUND AND PURPOSE: Studies have assessed PET by using various tracers to
      diagnose disease recurrence in patients with previously treated glioma; however,
      the accuracy of these methods, particularly compared with alternative imaging
      modalities, remains unclear. We conducted a meta-analysis to quantitatively
      synthesize the diagnostic accuracy of PET and compare it with alternative imaging
      modalities. MATERIALS AND METHODS: We searched PubMed and Scopus (until June
      2011), bibliographies, and review articles. Two reviewers extracted study
      characteristics, validity items, and quantitative data on diagnostic accuracy. We
      performed meta-analysis when >=5 studies were available. RESULTS: Twenty-six
      studies were eligible. Studies were heterogeneous in treatment strategies and
      diagnostic criteria of PET; recurrence was typically suspected by CT or MR
      imaging. The diagnostic accuracies of (18)F-FDG (n = 16) and (11)C-MET PET (n =
      7) were heterogeneous across studies. (18)F-FDG PET had a summary sensitivity of
      0.77 (95% CI, 0.66-0.85) and specificity of 0.78 (95% CI, 0.54-0.91) for any
      glioma histology; (11)C-methionine PET had a summary sensitivity of 0.70 (95% CI,
      0.50-0.84) and specificity of 0.93 (95% CI, 0.44-1.0) for high-grade glioma.
      These estimates were stable in subgroup and sensitivity analyses. Data were
      limited on (18)F-FET (n = 4), (18)F-FLT (n = 2), and (18)F-boronophenylalanine (n
      = 1). Few studies performed direct comparisons between different PET tracers or
      between PET and other imaging modalities. CONCLUSIONS: (18)F-FDG and (11)C-MET
      PET appear to have moderately good accuracy as add-on tests for diagnosing
      recurrent glioma suspected by CT or MR imaging. Studies comparing alternative
      tracers or PET versus other imaging modalities are scarce. Prospective studies
      performing head-to-head comparisons between alternative imaging modalities are
      needed.

PMID- 23124639
TI  - Radiation risk due to shunted hydrocephalus and the role of MR imaging-safe
      programmable valves.

PMID- 23124640
TI  - Postoperative changes in cerebral metabolites associated with cognitive
      improvement and impairment after carotid endarterectomy: a 3T proton MR
      spectroscopy study.
AB  - BACKGROUND AND PURPOSE: Cognitive function can improve or decline after carotid
      endarterectomy. Proton MR spectroscopy can be used evaluate cerebral metabolites,
      such as N-acetylaspartate, choline, and creatine, in vivo. The purpose of the
      present study was to determine whether postoperative changes in cerebral
      metabolites measured by using 3T proton MR spectroscopy were associated with
      changes in cognitive function after CEA. MATERIALS AND METHODS: In 100 patients
      undergoing CEA for ipsilateral cervical internal carotid artery stenosis (>=70%),
      brain proton MR spectroscopy was performed before and after surgery. NAA/Cr and
      Cho/Cr ratios were measured in regions of interest placed in the centrum
      semiovale of both cerebral hemispheres. Neuropsychological testing was also
      performed preoperatively and 1 month postoperatively. Multivariate statistical
      analysis of factors related to postoperatively changed cognition was performed,
      and odds ratios with 95% confidence intervals were calculated. RESULTS: On the
      basis of the neuropsychological assessments, 10 (10%), 80 (80%), and 10 (10%)
      patients were defined as having postoperatively improved, unchanged, and impaired
      cognition, respectively. A positive and high DeltaNAA/Cr ratio (postoperative
      value-preoperative value) in the cerebral hemisphere ipsilateral to the operative
      site was significantly associated with postoperatively improved cognition (95%
      CI, 13.3-21.3; P = .0016). Negative and high absolute values of the DeltaNAA/Cr
      ratio (95% CI, 0.018-0.101; P = .0039) and DeltaCho/Cr ratio (95% CI, 0.042
      0.135; P = .0046) in the ipsilateral cerebral hemisphere were significantly
      associated with postoperatively impaired cognition. CONCLUSIONS: Postoperative
      changes in cerebral metabolites measured by using proton MR spectroscopy were
      associated with changes in cognitive function after CEA.

PMID- 23124642
TI  - Treatment of acute vertebrobasilar occlusion using thrombectomy with stent
      retrievers: initial experience with 18 patients.
AB  - BACKGROUND AND PURPOSE: Acute vertebrobasilar occlusion is an ominous disease
      with few proved effective treatments. Experience with stent retrievers is scarce
      and limited to combined therapies (stent retrievers associated with previous
      intravenous fibrinolysis, intra-arterial thrombolysis, or other mechanical
      devices). We present our experience with 18 patients treated with direct
      thrombectomy by using stent retrievers. MATERIALS AND METHODS: Eighteen patients
      with vertebrobasilar occlusion were treated with direct thrombectomy by using
      stent retrievers at our hospital. The mean age was 67.5 years. Clinical
      presentation was sudden deterioration in consciousness level in 61.2% and
      progressive or fluctuating brain stem symptoms in 38.8%. Stroke subtype (TOAST)
      was atherothrombotic (33.3%), undetermined (33.3%), cardioembolic (27.7%), and of
      unusual etiology (5.5%). RESULTS: The occlusion site was the vertebral artery in
      1 case, proximal basilar artery in 4, middle basilar artery in 6, distal basilar
      artery in 5, and unilateral posterior cerebral artery in 2 cases. SRs included
      the Solitaire AB in 8 cases, Solitaire FR in 5 cases, and Trevo Pro in 5 cases.
      An 8F Merci balloon guide catheter was used in 15 patients, and a Neuron 6F, in 3
      patients. Post-clot retrieval definitive intracranial stents were used in 5
      patients (27.7%). Postprocedural TICI >= 2b was achieved in 17 patients (94.4%).
      Clinically, 72.2% of patients experienced an improved NIHSS score at discharge,
      22.2% died, and in 5.5% the NIHSS scores did not change. The mRS score at 3
      months was 0-2 in 9 patients (50%) and 3-5 in 5 patients (27.7%). CONCLUSIONS:
      Thrombectomy with stent retrievers is feasible in the treatment of
      vertebrobasilar occlusion. These initial results must be confirmed by further
      prospective studies with a larger number of cases.

PMID- 23124641
TI  - A DSA-based method using contrast-motion estimation for the assessment of the
      intra-aneurysmal flow changes induced by flow-diverter stents.
AB  - BACKGROUND AND PURPOSE: Flow-diverter stents modify intra-aneurysmal blood flow
      and induce the progressive thrombosis of intracranial aneurysms followed by
      stable vascular reconstruction. The aim of this study was to report a new method
      for the appraisal of intracranial blood flow from DSA performed during
      endovascular treatment procedures. MATERIALS AND METHODS: A cohort of 24 patients
      with unruptured IAs who underwent FDS implantation was prospectively recruited.
      Pre- and post-DSA sequences in combination with 3D rotational angiography were
      acquired. The quantification of arterial and intra-aneurysmal flow was
      accomplished by using an optical flow approach. Flow reduction was assessed by
      using a new metric termed the mean aneurysm flow amplitude ratio. The correlation
      between the MAFA ratio and the incidence of aneurysm thrombosis was assessed by
      using receiver operating characteristic analysis and the Fisher exact test when
      the optimum Youden index was found. RESULTS: The quantification of flow was
      successfully achieved in 21 of 24 patients (87.5%). On the imaging follow-up, 18
      aneurysms developed complete thrombosis (87.5%) and 3 displayed residual
      circulation (12.5%). The threshold analysis of the MAFA ratio significantly
      predicted thrombosis at 12 months below a threshold of 1.03 (P=.035). There was
      no significant correlation between the time for complete occlusion of the
      aneurysm and contrast stagnation inside the aneurysm after treatment (P>.05).
      CONCLUSIONS: The MAFA ratio based on DSA flow quantification appears to be a
      reliable predictor for the assessment of stent treatment outcomes in this small
      study. These results open the door for perioperative flow quantification and
      provide indices that may help clinicians make appropriate intraprocedural
      decisions.

PMID- 23124643
TI  - CT perfusion spot sign improves sensitivity for prediction of outcome compared
      with CTA and postcontrast CT.
AB  - BACKGROUND AND PURPOSE: Recent studies have recommended both early and late
      imaging to increase spot sign detection. However optimal acquisition timing for
      spot detection and impact on outcome prediction is uncertain. Our aim was to
      assess the utility of CTP in spot sign detection and characterization with
      emphasis on its impact on the prediction of outcome in patients with acute
      primary ICH. MATERIALS AND METHODS: A retrospective review of 28 patients
      presenting within 6 hours of ICH, studied with CTA, CTP, and postcontrast CT, was
      performed. CTA, CTP, and postcontrast CT spot sign characteristics were recorded
      according to predefined radiologic criteria. A combined primary outcome of
      hematoma expansion or poor clinical outcome was used and defined as hematoma
      expansion >=6 mL or >=30%, need for surgical drainage, or in-hospital mortality.
      Associations with the primary outcome and spot sign presence were examined
      against baseline clinical, laboratory, and radiographic variables. Predictive
      ability of CTA, CTP, and postcontrast CT spot characteristics were compared among
      modalities. RESULTS: Primary outcome criteria were met in 18 patients (61%). CTP
      spot sign presence was an independent predictor of hematoma expansion or poor
      outcome (P = .040) and demonstrated greater sensitivity (78%) than spots detected
      on CTA (44%, P = .034) and postcontrast CT (50%, P = .025). Specificity and
      positive predictive value of the spot sign was high (100%) on all modalities. CTP
      detected the greatest number of spots (80%) with peak spot attenuation
      demonstrated at a median (interquartile range) time of 50 seconds (range, 34-63
      seconds) after contrast bolus injection. CTP spot appearance was later than CTA
      detected spots (P = .002) and earlier than postcontrast CT spots (P < .001).
      CONCLUSIONS: CTP spot sign detection improves the sensitivity for prediction of
      outcome compared with CTA or postcontrast CT-detected spots.

PMID- 23124645
TI  - Whither the gonads? (Comment on DOI 10.1002/bies.201200081).

PMID- 23124644
TI  - Anatomic MR imaging and functional diffusion tensor imaging of peripheral nerve
      tumors and tumorlike conditions.
AB  - BACKGROUND AND PURPOSE: A number of benign and malignant peripheral nerve tumor
      and tumorlike conditions produce similar imaging features on conventional
      anatomic MR imaging. Functional MR imaging using DTI can increment the diagnostic
      performance in differentiation of these lesions. Our aim was to evaluate the role
      of 3T anatomic MR imaging and DTI in the characterization of peripheral nerve
      tumor and tumorlike conditions. MATERIALS AND METHODS: Twenty-nine patients (13
      men, 16 women; mean age, 41+/-18 years; range, 11-83 years) with a nerve tumor or
      tumorlike condition (25 benign, 5 malignant) underwent 3T MR imaging by using
      anatomic (n=29), functional diffusion, DWI (n=21), and DTI (n=24) techniques.
      Images were evaluated for image quality (3-point scale), ADC of the lesion,
      tractography, and fractional anisotropy of nerves with interobserver reliability
      in ADC and FA measurements. RESULTS: No significant differences were observed in
      age (benign, 40+/-18 versus malignant, 45+/-19 years) and sex (benign,
      male/female=12:12 versus malignant, male/female=3:2) (P>.05). All anatomic
      (29/29, 100%) MR imaging studies received "good" quality; 20/21 (95%) DWI and
      21/24 (79%) DTI studies received "good" quality. ADC of benign lesions (1.848+/
      0.40*10(-3) mm2/s) differed from that of malignant lesions (0.900+/-0.25*10(-3)
      mm2/s, P<.001) with excellent interobserver reliability (ICC=0.988 [95% CI, 0.976
      0.994]). There were no FA or ADC differences between men and women (P>.05). FA of
      involved nerves was lower than that in contralateral healthy nerves (P<.001) with
      excellent interobserver reliability (ICC=0.970 [95% CI, 0.946-0.991]). ADC on DTI
      and DWI was not statistically different (P>.05), with excellent intermethod
      reliability (ICC=0.943 [95% CI, 0.836-0.980]). Tractography differences were
      observed in benign and malignant lesions. CONCLUSIONS: 3T MR imaging and DTI are
      valuable methods for anatomic and functional evaluation of peripheral nerve
      lesions with excellent interobserver reliability. While tractography and low FA
      provide insight into neural integrity, low diffusivity values indicate malignancy
      in neural masses.

PMID- 23124648
TI  - Phase 1 study of trebananib (AMG 386), an angiogenesis targeting angiopoietin-1/2
      antagonist, in Japanese patients with advanced solid tumors.
AB  - PURPOSE: To evaluate the safety, tolerability, pharmacokinetics, and antitumor
      activity of trebananib (AMG 386)--a first-in-class angiopoietin-1/2 antagonist
      peptide-Fc fusion protein--in Japanese patients, we conducted a phase 1, dose
      escalation study. METHODS: Eligible patients were men or women, aged between 20
      and 74 years, who had histologically or cytologically confirmed advanced solid
      tumors refractory to standard treatment. Trebananib (3, 10, and 30 mg/kg) was
      administered intravenously over 60 min in weekly cycles. RESULTS: From June 2009
      to April 2010, a total of 18 patients (6 for each dose cohort) were enrolled into
      the study. Trebananib was tolerated at all dose levels. No dose-limiting
      toxicities were observed. The most common adverse events were peripheral edema,
      constipation, fatigue, and pyrexia. Exposure to trebananib appeared to increase
      according to the dose administered. Serum clearance appeared to be similar across
      the dose range with the mean terminal-phase half-life ranging from 93.9 to 95.9
      h. No neutralizing antibodies were detected. Tumor response was assessed in 18
      patients. Of these, one patient with colon cancer in the 3-mg/kg cohort and one
      with bladder cancer in the 30-mg/kg cohort had partial responses as their best
      responses. These 2 patients were on treatment at the time of data cutoff (January
      17, 2012). CONCLUSION: Trebananib was tolerated and showed acceptable safety
      profile in Japanese patients with advanced solid tumors. The pharmacokinetic
      profiles were similar to those in the previous studies in the United States.
      Trebananib also showed evidence of durable antitumor activity in some patients.

PMID- 23124649
TI  - Phase II study of nedaplatin and irinotecan in patients with extensive small-cell
      lung cancer.
AB  - BACKGROUND: The standard chemotherapy for Japanese patients with extensive
      disease of small-cell lung cancer (ED-SCLC) is cisplatin and irinotecan. METHODS:
      Patients with untreated ED-SCLC were treated with nedaplatin (NP) at 50 mg/m(2)
      and irinotecan (CPT) at 50 mg/m(2) on days 1 and 8 every 4 weeks for four cycles.
      RESULTS: Twenty-five patients were registered. Nineteen patients were male and
      six female, with a median age of 64 years (50-79 years). Two patients had a
      performance status of 2. Nineteen of them were able to receive 4 courses of NP
      and CPT chemotherapy. Grade 3 or 4 anemia, neutropenia, and thrombocytopenia
      occurred in 8.0, 68.0, and 36.0 % of patients, respectively. Other grade 3
      toxicities were SGOT, hyponatremia, fatigue, vomiting, diarrhea, hypotension,
      febrile neutropenia, oral hemorrhage, and pneumonia. Grade 4 fatigue occurred in
      one patient. There was no treatment-related death. The overall response rate was
      100 %. The median progression-free and overall survivals were 6.6 and 16.0
      months, respectively, and the 2-year survival rate was 28 %. CONCLUSION: NP with
      CPT is effective and safe for patients with ED-SCLC.

PMID- 23124646
TI  - An update on spinal cord injury research.
AB  - Spinal cord injury (SCI) can have a range of debilitating effects and permanently
      alter the capabilities and quality of life of survivors. The first specialized
      centers of care for SCI were established in 1944 and since then an increasing
      amount of research has been carried out in this area. Despite this, the present
      treatment and care levels for SCI are not comparable to those in other areas of
      medicine. In the clinic, the aim of SCI treatment is primarily to limit secondary
      damage by reducing compression in trauma spots and stabilizing the spinal column.
      Currently, no effective strategy for functional recovery is offered. In this
      review, we focus on research progress on the molecular mechanisms underlying SCI,
      and assess the treatment outcomes of SCI in animal models, i.e., neurotrophins
      and stem cells are discussed as pre-clinical therapies in animal models. We also
      assess the resources available and national research projects carried out on SCI
      in China in recent years, as well as making recommendations for the future
      allocation of funds in this area.

PMID- 23124647
TI  - Neuroimaging studies of bilingual expressive language representation in the
      brain: potential applications for magnetoencephalography.
AB  - Bilingualism is the ability to use two or more languages with equal or near equal
      fluency. How the brain, often seamlessly, selects, controls, and switches between
      languages is an enigma. Neuroimaging studies offer the unique opportunity to
      probe the mechanisms underlying bilingual brain function. Non-invasive methods,
      in particular, functional MRI (fMRI) and event-related potentials (ERPs), have
      allowed examination in healthy control populations. Whole-head
      magnetoencephalography (MEG), a relatively new addition to the cadre of
      neuroimaging tools, offers a combination of the high spatial resolution of fMRI
      with the high temporal resolution of ERPs. Thus far, MEG has been applied to the
      studies of bilingual receptive language, or bilingual language comprehension. MEG
      has not yet been applied to the study of bilingual language production as such
      studies have faced more challenges (see Salmelin, 2007 for a review), and these
      have only recently been addressed. Here, we review the literature on MEG
      expressive language studies and point out a direction for the application of MEG
      to the study of bilingual language production.

PMID- 23124651
TI  - Software for automated MRI-based quantification of abdominal fat and preliminary
      evaluation in morbidly obese patients.
AB  - PURPOSE: To present software for supervised automatic quantification of visceral
      and subcutaneous adipose tissue (VAT, SAT) and evaluates its performance in terms
      of reliability, interobserver variation, and processing time, since fully
      automatic segmentation of fat-fraction magnetic resonance imaging (MRI) is fast
      but susceptible to anatomical variations and artifacts, particularly for advanced
      stages of obesity. MATERIALS AND METHODS: Twenty morbidly obese patients (average
      BMI 44 kg/m(2) ) underwent 1.5-T MRI using a double-echo gradient-echo sequence.
      Fully automatic analysis (FAA) required no user interaction, while supervised
      automatic analysis (SAA) involved review and manual correction of the FAA results
      by two observers. Standard of reference was provided by manual segmentation
      analysis (MSA). RESULTS: Average processing times per patient were 6, 6+4, and 21
      minutes for FAA, SAA, and MSA (P < 0.001), respectively. For VAT/SAT assessment,
      Pearson correlation coefficients, mean (bias), and standard deviations of the
      differences were R = 0.950, +0.003, and 0.043 between FAA and MSA and R = 0.981,
      +0.009, and 0.027 between SAA and MSA. Interobserver variation and intraclass
      correlation were 3.1% and 0.996 for SAA, and 6.6% and 0.986 for MSA,
      respectively. CONCLUSION: The presented supervised automatic approach provides a
      reliable option for MRI-based fat quantification in morbidly obese patients and
      was much faster than manual analysis.

PMID- 23124650
TI  - The role of sleep problems in central pain processing in rheumatoid arthritis.
AB  - OBJECTIVE: Among rheumatoid arthritis (RA) patients, the intensity of pain may be
      out of proportion to the severity of peripheral inflammation. This observation
      suggests that mechanisms of central nervous system pain amplification, such as
      diminished conditioned pain modulation (CPM), may play a role in enhancing pain
      perception among some RA patients. This study was undertaken to examine the level
      of CPM, pressure-pain threshold, and pressure-pain tolerance among RA patients
      compared to healthy controls. METHODS: Fifty-eight female RA patients and 54 age
      matched female control subjects without chronic pain underwent quantitative
      sensory testing (QST) to assess CPM levels, pressure-pain thresholds, and
      pressure-pain tolerance levels. CPM was induced using a cold water bath, and the
      pain threshold (when patients first felt pain) and pain tolerance (when pain was
      too much to bear) were assessed with an algometer. Associations between RA and
      each QST outcome were analyzed using linear regression. Sleep problems, mental
      health, and inflammation were assessed as mediators of the relationship between
      RA and QST outcomes. RESULTS: The median CPM level was 0.5 kg/cm2 (interquartile
      range [IQR] -0.1, 1.6) among RA patients, compared to a median of 1.5 kg/cm2 (IQR
      -0.1, 2.5) among controls (P=0.04). RA patients, compared to controls, had a
      lower pain threshold and lower pain tolerance at the wrists (each P<=0.05). In
      addition, RA patients had greater problems with sleep, pain catastrophizing,
      depression, and anxiety (P<0.0001 versus controls). Results of mediation analyses
      suggested that low CPM levels might be attributed, in part, to sleep disturbance
      (P=0.04). CONCLUSION: RA patients have impaired CPM when compared to pain-free
      control subjects. Sleep problems may mediate the association between RA and
      attenuated CPM.

PMID- 23124652
TI  - The Notch1/cyclooxygenase-2/Snail/E-cadherin pathway is associated with hypoxia
      induced hepatocellular carcinoma cell invasion and migration.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide;
      however, the prognosis of HCC patients remains poor. This poor prognosis is
      mainly attributed to the high rate of intrahepatic and distant metastasis. HCC
      often occurs in a hypoxic environment and hypoxia can activate metastatic
      programs, ultimately leading to tumor recurrence or metastasis. Thus, the
      discovery and subsequent development of novel agents to block HCC invasion and
      migration are the primary objectives of hepatic cancer research. The Notch1
      signaling pathway might be involved in hypoxia-induced carcinoma metastasis.
      However, the mechanisms by which Notch1 mediates cell metastasis, particularly in
      hepatocellular carcinoma, are not yet entirely clear. The results of the present
      study show that hypoxia increases the invasion and migration capacities of
      different HCC cells. Activation of the Notch1 signaling pathway contributes to
      hypoxia-induced invasion and migration in HCC cells. The activated Notch1
      signaling pathway can regulate Snail/E-cadherin through cyclooxygenase-2 (COX-2)
      under hypoxic conditions. The above results suggest that the Notch1/COX-2/Snail/E
      cadherin pathway is possibly associated with hypoxia-induced invasion and
      migration in HCC cells. Thus, targeting Notch1 may be useful for devising novel
      preventive and therapeutic strategies for HCC.

PMID- 23124653
TI  - Vitamin K2 administration is associated with decreased disease activity in
      patients with rheumatoid arthritis.
AB  - OBJECTIVES: Vitamin K2 (VitK2) is reported to induce not only bone mineralization
      of human osteoblasts and apoptosis of osteoclasts, but also apoptosis of
      rheumatoid arthritis (RA) synovial cells, while its clinical effect on disease
      activity of RA remains unknown. METHODS: 158 female RA patients (mean age 62.5
      years) who had not been treated with warfarin, biologics, or teriparatide were
      enrolled in this study. VitK2 (45 mg/day) was administered in 70 patients with a
      serum undercarboxylated osteocalcin level of >4.5 ng/ml or with decreased bone
      mineral density in spite of the treatment with other anti-osteoporosis
      medications, regardless of RA disease activity. A longitudinal study was
      conducted in 52 patients who were additionally treated with VitK2 without
      changing their other medications for three months. RESULTS: In the cross
      sectional study, as compared to the VitK2-naive group (n = 88), the VitK2-treated
      group (n = 70) showed lower serum CRP (1.7 +/- 0.2 vs. 0.5 +/- 0.1 mg/dl; P <
      0.001), MMP-3 (220.4 +/- 21.9 vs. 118.0 +/- 14.4 ng/ml; P < 0.001), and DAS28-CRP
      (2.9 +/- 0.1 vs. 2.4 +/- 0.1; P < 0.05). In the longitudinal study, patients who
      were additionally treated with VitK2 showed significant decreases in serum CRP
      (1.1 +/- 0.2 to 0.6 +/- 0.2 mg/dl; P < 0.001), MMP-3 (160.1 +/- 25.6 to 125.0 +/-
      17.8 ng/ml; P < 0.05), and DAS28-CRP (3.1 +/- 0.2 to 2.4 +/- 0.1; P < 0.001).
      CONCLUSIONS: VitK2 may have the potential to improve disease activity besides
      osteoporosis in RA.

PMID- 23124654
TI  - Evaluating agarwood products for 2-(2-phenylethyl)chromones using direct analysis
      in real time time-of-flight mass spectrometry.
AB  - RATIONALE: Agarwood is the resinous material harvested from threatened Aquilaria
      species. We investigated how many protonated 2-(2-phenylethyl)chromone ions were
      sufficient to make an accurate identification of agarwood. Analysis of 125
      reference samples was carried out by direct analysis in real time time-of-flight
      mass spectrometry (DART-TOFMS). The identification criteria developed were
      applied to commercial samples. METHODS: We developed a technique that uses DART
      TOFMS to detect 2-(2-phenylethyl)chromones. Additionally, we developed a set of
      criteria to infer the presence of Aquilaria in commercial samples of wood chips,
      sawdust, incense and liquids. Additionally, we examined other fragrant woods to
      determine if they contained a chemical profile that could be falsely identified
      as agarwood. RESULTS: Analysis of reference and commercial samples (n = 151)
      established that DART-TOFMS provides reproducible mass spectra that are useful
      for inferring the genus of suspected agarwood samples. We identified 17 ions
      which were useful for authenticating agarwood. Comparison of the number of
      chromone ions detected by direct analyses of dry wood chips versus eluent
      analysis of methanol-extracted wood showed that results were similar. Lastly,
      analysis of 25 scented woods of other species did not give false positive
      results. CONCLUSIONS: Reliable criteria for inferring agarwood include the
      presence of diagnostic ions, m/z 319.118 or 349.129, in addition to ten or more
      ions characteristic of 2-(2-phenylethyl)chromones. Wood anatomists challenged
      with difficult morphological identifications can use this tool to assist in their
      analyses. Published 2012. This article is a US Government work and is in the
      public domain in the USA.

PMID- 23124655
TI  - How large is large: estimating ecologically meaningful isotopic differences in
      observational studies of wild animals.
AB  - RATIONALE: In ecological studies of wildlife movements and foraging, bio-logging
      and isotopic data are routinely collected and increasingly analyzed in tandem.
      Such analyses have two shortcomings: (1) small sample size linked with the number
      of telemetric tags that can be deployed, and (2) the observational nature of
      isotopic gradients. Wildlife ecologists are thus put in a statistical conundrum
      known as the small n, large p problem. METHODS: Using shrinkage regression, which
      directly addresses the issue of accurately estimating effects from sparse data,
      we studied what counts as a biologically meaningful isotopic difference (a
      prerequisite to delineate isoscapes) in the southern elephant seal (Mirounga
      leonina), a large and elusive marine predator. RESULTS: Seals foraging in
      Antarctic waters had a lower carbon isotopic value (by ~ 20/00) than seals
      foraging either in the interfrontal zone or on the Kerguelen Plateau. The latter
      two foraging strategies were indistinguishable on the sole basis of delta(13) C
      values with our data. CONCLUSIONS: Shrinkage regression is a conservative
      statistical technique that has wide applicability in isotopic ecology to help
      separate robust biological signals from noise.

PMID- 23124656
TI  - Rapid screening of synthetic cathinones as trace residues and in authentic
      seizures using a portable mass spectrometer equipped with desorption electrospray
      ionization.
AB  - RATIONALE: Recently, the surge in synthetic cathinone abuse has become a matter
      of public concern. With the influx of confiscated synthetic cathinones
      dramatically on the rise, laboratory workloads are expected to increase at a
      similar rate. This prompts the need for rapid analytical methods capable of
      detecting and identifying such compounds. METHODS: A ruggedized, portable ion
      trap mass spectrometer capable of desorption electrospray ionization mass
      spectrometry (DESI-MS) was used to rapidly characterize various synthetic
      cathinones. Target analytes were directly analyzed as trace residues on various
      substrates and as major components in authentic, powder-based forensic evidence.
      Physical transfer swabs can also be examined with this method, allowing efficient
      screening of large areas and geometrically complex samples. RESULTS: Method
      validity was tested on trace residues, mock forensic samples, and authentic
      evidentiary seizures, yielding low- to sub-ng detection limits from several
      substrates of interest to crime scene investigation. Analyte confirmation was
      accomplished through MS(2) analysis, providing characteristic fragmentation
      similar to that reported in literature. High-throughput analysis was demonstrated
      with no significant instrumental carryover, even for powdered samples. The
      robustness of this DESI-MS method to multi-component samples was examined, marked
      by high chemical specificity. CONCLUSIONS: Coupling DESI-MS with portable
      instrumentation allowed sensitive and selective examination of synthetic
      cathinones from various substrates, in complex mixtures, and directly from mock
      and authentic forensic evidence. This instrumental method has the potential to
      assess the evidentiary value of forensic samples at crime scenes, reducing
      backlogs and expediting criminal investigations.

PMID- 23124657
TI  - Electrospray ionisation mass spectrometry molecular-level structural
      characterisation of novel phenoxycarboxylic acid-oligo(3-hydroxybutyrate)
      conjugates with potential agricultural applications.
AB  - RATIONALE: Due to the low resistance of forms of pesticides to environmental
      conditions, agrochemicals frequently do not reach their objective, which may
      cause environmental pollution. The minimisation of the adverse effects of
      pesticides requires the development of a system for their long-term controlled
      release. In the present work, we report the synthesis and structural studies of
      novel controlled-release pesticide-oligo-3-hydroxybutyrate systems with potential
      agricultural applications. METHODS: The novel controlled-release pesticide
      oligo(3-hydroxybutyrate) systems were obtained via the anionic ring-opening
      oligomerisation of (R,S)-beta-butyrolactone initiated by the potassium salt of
      selected pesticides. Electrospray ionisation mass spectrometry (ESI-MS(n))
      analyses in positive-ion mode, supported by (1)H NMR results, were used for the
      structural characterisation of the obtained conjugates. The presence of the
      respective pesticides in an unchanged form associated with oligo-3
      hydroxybutyrate chains was confirmed by ESI-MS/MS experiments performed for
      selected pesticide-oligo(3-hydroxybutyrate) ions and by the subsequent
      investigation of their fragmentation pathways. RESULTS: The structures of the
      resulting conjugates were established at the molecular level with the aid of ESI
      MS(n). The presence of one and two chlorine atoms (derived from MCPA and 2,4-D
      pesticides) in the conjugates studied was confirmed by comparison of the
      calculated and experimental isotopic profiles for the selected ions of the
      respective conjugates. The fragmentation of the selected ions of the resulting
      conjugates confirmed that the respective pesticides are covalently bonded with
      oligo(3-hydroxybutyrate) through a hydrolysable ester bond. CONCLUSIONS: An
      analytical method has been developed for the characterisation of new pesticide
      oligo(3-hydroxybutyrate) conjugates. A detailed NMR and MS structural
      characterisation of the designed controlled-release system of the pesticides was
      performed. These results are important in the analysis of designed biodegradable
      polymeric conjugates with potential agricultural applications.

PMID- 23124659
TI  - Quantifying the abundance and stable isotope composition of pyrogenic carbon
      using hydrogen pyrolysis.
AB  - RATIONALE: Pyrogenic carbon (C(P)) is an important component of the global carbon
      budget. Accurate determination of the abundance and stable isotope composition of
      C(P) in soils and sediments is crucial for understanding the dynamics of the C(P)
      cycle and interpreting records of biomass burning, climate and vegetation change
      in the past. Here we test hydrogen pyrolysis (hypy) as a new technique
      potentially capable of eliminating labile organic carbon (C(L)) from total
      organic carbon (C(T)) in a range of matrices in order to enable reliable
      quantification of both the C(P) component of C(T) and the stable carbon isotope
      composition of C(P) (delta(13)C(P)). METHODS: We mixed C(P) at a range of
      concentrations with common C(P)-free matrices (C(L) = cellulose, chitin, keratin,
      decomposed wood, leaf litter, grass and algae) and determined the amount of
      residual carbon not removed by hydrogen pyrolysis (C(R)) as a ratio of C(T)
      (C(R)/C(T)). Mixing C(P) with a unique delta(13)C value provided a natural
      abundance isotope label from which to precisely determine the ratio of C(P) to
      residual C(L) remaining after hypy. RESULTS: All C(P)-free matrices contained
      trace carbon after hypy, indicating that hypy does not remove all the C(L).
      However, there was a strong correlation between C(R)/C(T) and C(P)/C(T), viz.
      C(R)/C(T)= 1.02(C(P)/C(T)) + 4.0 * 10(-3), r(2) = 0.99, p <0.001, suggesting that
      only a small and reasonably constant fraction of C(L) remains after hypy.
      Uncertainties associated with the correction for contamination of C(R) by
      residual C(L) are minimal allowing for reliable determinations of both C(P) and
      delta(13)C(P) in many cases. CONCLUSIONS: Hydrogen pyrolysis appears to be a
      robust technique for estimating C(P) abundance and delta(13)C(P) across a range
      of materials. Nevertheless, caution is required in interpreting delta(13)C(P)
      values when C(P)/C(T) is low, with C(P)/C(T)>4% being required for the
      determination of the delta(13)C(P) values within an interpretable error under our
      experimental conditions.

PMID- 23124658
TI  - Effect of 20(S)-ginsenoside Rg3 on streptozotocin-induced experimental type 2
      diabetic rats: a urinary metabonomics study by rapid-resolution liquid
      chromatography/mass spectrometry.
AB  - RATIONALE: 20(S)-ginsenoside Rg3 is an active component of Panax ginseng. It is
      known that 20(S)-ginsenoside Rg3 has a protective effect against hyperglycemia,
      obesity and diabetes in vivo, but the precise mechanisms of these actions have
      not yet been entirely elucidated. METHODS: A urinary metabonomics method based on
      rapid-resolution liquid chromatography/mass spectrometry (RRLC/MS) was developed
      to investigate the effect of 20(S)-ginsenoside Rg3 on type 2 diabetic rats.
      RESULTS: With multivariate statistical analysis, a clear separation between type
      2 diabetic rats and those treated with 20(S)-ginsenoside Rg3 was achieved. Six
      potential biomarkers were found and identified. CONCLUSIONS: This work shows that
      the mechanism of the effect of 20(S)-ginsenoside Rg3 on type 2 diabetes may be
      involved with the regulation of nucleic acid metabolism, energy metabolism and
      gut flora metabolism.

PMID- 23124660
TI  - Simultaneous multiple mycotoxin quantification in feed samples using three
      isotopically labeled internal standards applied for isotopic dilution and data
      normalization through ultra-performance liquid chromatography/electrospray
      ionization tandem mass spectrometry.
AB  - RATIONALE: Mycotoxins are typically present in grain and are also concentrated in
      distillers dried grains with solubles (DDGS), common feed ingredients for food
      animals. The diversity of mycotoxins and feed matrices has made the routine
      detection and quantification of mycotoxins in feed both complex and prohibitively
      expensive. METHODS: Ultra-performance liquid chromatography/electrospray
      ionization triple quadrupole detection (UPLC/ESI-TQD) (tandem mass spectrometry,
      MS/MS) with (13) C-labeled isotopic dilution was used to analyze internal
      standard isotopologues of three mycotoxin molecules, as well as 29 other
      structurally differing mycotoxin molecules from four common feed matrices: corn,
      wheat, barley, or DDGS. Mycotoxins were extracted via a single-step procedure
      using a mixture of acetonitrile/water/formic acid. Labeled isotopologues were
      used as a surrogate to account for extraction quality and as internal standards
      for the evaluation of the feed matrix signal suppression/enhancement (SSE)
      contributed by each mycotoxin and by each matrix. The SSE was corrected by matrix
      matched calibration with blank certified reference feed material. RESULTS: The
      limits of detection for individual mycotoxins in buffer ranged from 0.01 to 206.7
      ug/mL but could increase by up to four times depending on the matrix effect. The
      accuracy and precision were enhanced by the use of isotopically labeled
      standards. The recoveries were somewhat negatively affected by the SSE
      contributed by each matrix. Each mycotoxin was successfully detected and assigned
      to one of four SSE categories: high (-66%), intermediate (-48%), low (-19%)
      signal suppression and signal enhancement (> +300%). CONCLUSIONS: An improved
      LC/MS method was validated, which offers a practical and economical means for
      large-scale detection and quantification of multiple mycotoxins in common animal
      feed matrices, including DDGS.

PMID- 23124661
TI  - Determination of stimulants using gas chromatography/high-resolution time-of
      flight mass spectrometry and a soft ionization source.
AB  - RATIONALE: The aim of this study was to investigate the mass spectral
      fragmentation of a small set of stimulants in a high-resolution time-of-flight
      mass spectrometer equipped with a soft ionization source using vacuum ultraviolet
      (VUV) photons emitted from different plasma gases. It was postulated that the use
      of a plasma gas such as Xe, which emits photons at a lower energy than Kr or Ar,
      would lead to softer ionization of the test compounds, and thus to less
      fragmentation. METHODS: A set of nine stimulants: cocaine, codeine, nicotine,
      methadone, phenmetrazine, pentylenetetrazole, niketamide, fencamfamine, and
      caffeine, was analyzed by gas chromatography/time-of-flight mass spectrometry
      (GC/TOFMS) in positive ion mode with this soft ionization source, using either
      Xe, Kr, or Ar as plasma gases. Working solutions of the test compounds at 0.1 to
      100 ng/MUL were used to establish instrument sensitivity and linearity. RESULTS:
      All test compounds, except methadone and pentylenetetrazole, exhibited strong
      molecular ions and no fragmentation with Xe-microplasma photoionization (MPPI).
      Methadone exhibited significant fragmentation not only with Xe, but also with Kr
      and Ar, and pentylenetetrazole could not be ionized with Xe, probably because its
      ionization energy is above 8.44 eV. The Kr- and Ar-MPPI mass spectra of the test
      compounds showed that the relative intensity of the molecular ion decreased as
      the photon energy increased. CONCLUSIONS: When coupled to a TOF mass spectrometer
      this soft ionization source has demonstrated signal-to-noise (S/N) ratios from 7
      to 730 at 100 pg per injection (depending on the compound), and a dynamic range
      of three orders of magnitude (100 pg to 100 ng) for some of the test compounds.

PMID- 23124662
TI  - Scanning probe electrospray ionization for ambient mass spectrometry.
AB  - RATIONALE: Ambient sampling and ionization techniques have been attracting
      attention in imaging mass spectrometry because they offer the advantage of rapid
      testing. We have developed a method which exploits the fluid motion of charged
      solvents for both local sampling and ionization with a single vibrating capillary
      probe. METHODS: The capillary probe was used to supply solvents in order to form
      a liquid bridge between the probe and a sample surface. A bias voltage was
      applied to the solvents to generate electrospray ionization (ESI). The probe was
      also vibrated by either an ultrasonic transducer fixed at the back of the sample
      (contact-mode) or spontaneous vibration of probe itself (tapping-mode). The ions
      generated by ESI were detected by a triple quadrupole mass spectrometer. RESULTS:
      Sampling of the specimens at the liquid bridge and ESI of the dissolved solutions
      both occurred around the probe apex. The sampling and ionization co-existed in
      contact-mode, while they were explicitly separated in the tapping-mode. The one
      dimensional mapping of solid samples such as protein films and tissue sections
      was demonstrated. The results indicated that there was little cross-contamination
      during the operation. CONCLUSIONS: The method, named scanning probe electrospray
      ionization (SPESI), promises to be a simple and unique approach toward direct
      sampling and ionization methodology.

PMID- 23124663
TI  - High-precision measurements of 17O/16O and 18O/16O ratios in CO2.
AB  - RATIONALE: Measurements of delta(17)O and delta(18)O values of tropospheric CO(2)
      are of great importance. However, to be useful, such measurements must be an
      order of magnitude more precise than in current published literature. With this
      purpose we developed a new method for high-precision mass spectrometric
      measurements of (17)O/(16)O and (18)O/(16)O ratios in CO(2), which is presented
      in this study. METHODS: The method is based on isotopic exchange equilibration
      between H(2)O and CO(2) in sealed glass ampoules followed by water fluorination
      to produce O(2). Dual inlet isotope ratio mass spectrometric (IRMS) measurements
      of the delta(17)O and delta(18)O values of this O(2) allow delta(17)O values of
      CO(2) to be obtained with very high precision (0.01 to 0.03 0/00). This method
      requires about 70 umol of CO(2). RESULTS: Measurements of standard CO(2) gas and
      atmospheric CO(2) yield reproducibility of 0.01 to 0.03 0/00 for both delta(17)O
      and delta(18)O values, and 5 per meg for (17)O(excess). Fractionation factors
      (17)alpha and (18)alpha were determined in the H(2)O-CO(2) equilibrium at 25 
      degrees C as 1.021254 +/- 0.00004 and 1.041036 +/- 0.00008, respectively, and the
      ratio ln(17)alpha/ln(18)alpha as 0.5229 +/- 0.0001. CONCLUSIONS: The results
      demonstrate that the new method is the most accurate analytical procedure ever
      presented for measurements of (17)O(excess) of CO(2) gas. It is suitable for
      measurements of CO(2) extracted from relatively small samples of air (~5 L), and
      is thus useful for monitoring the (17)O(excess) of CO(2) on a broad global scale.

PMID- 23124664
TI  - Hydrogen scrambling in non-covalent complexes of peptides.
AB  - RATIONALE: Mass spectrometry analysis combined with hydrogen-deuterium exchange
      (HDX-MS) is arising as a tool for quick analysis of native protein conformation.
      However, during collision-induced dissociation (CID) the spatial distribution of
      deuterium is not always conserved. It is therefore important to find out how
      hydrogen scrambling occurs--this study concentrates on the possibility of
      scrambling between amino acid residues spatially close together, but not
      connected by covalent bonds. METHODS: Peptides used in this study were
      synthesized by Fmoc strategy. Deuteration occurred in ammonia formate solution in
      D(2)O. Non-covalent complexes consisting of a deuterated and a non-deuterated
      peptide were analyzed by electrospray ionization (ESI) Fourier transform ion
      cyclotron resonance (FT-ICR-MS) with quadrupole mass filter. Low-energy CID was
      used for complex dissociation. RESULTS: The complexes were isolated on a
      quadrupole and subjected to CID to cause dissociation. The deuterium distribution
      before and after the dissociation of a non-covalent complex to its components was
      measured. The study revealed that no significant scrambling occurred between the
      constituents of the complexes--the degree of scrambling did not exceed 10%.
      CONCLUSIONS: The results obtained for the complexes should be similar to those
      for protein parts spatially close together--hydrogen scrambling between them
      should be negligible. The knowledge that almost all the scrambling occurs along
      peptide chains gives a better insight into the mechanism of HDX inside a protein.

PMID- 23124665
TI  - Accounting for the effects of lipids in stable isotope (delta13C and delta15N
      values) analysis of skin and blubber of balaenopterid whales.
AB  - RATIONALE: Stable isotope values (delta(13)C and delta(15)N) of darted skin and
      blubber biopsies can shed light on habitat use and diet of cetaceans, which are
      otherwise difficult to study. Non-dietary factors affect isotopic variability,
      chiefly the depletion of (13)C due to the presence of (12)C-rich lipids. The
      efficacy of post hoc lipid-correction models (normalization) must be tested.
      METHODS: For tissues with high natural lipid content (e.g., whale skin and
      blubber), chemical lipid extraction or normalization is necessary. C:N ratios,
      delta(13)C values and delta(15)N values were determined for duplicate control and
      lipid-extracted skin and blubber of fin (Balaenoptera physalus), humpback
      (Megaptera novaeangliae) and minke whales (B. acutorostrata) by continuous-flow
      elemental analysis isotope ratio mass spectrometry (CF-EA-IRMS). Six different
      normalization models were tested to correct delta(13)C values for the presence of
      lipids. RESULTS: Following lipid extraction, significant increases in delta(13)C
      values were observed for both tissues in the three species. Significant increases
      were also found for delta(15)N values in minke whale skin and fin whale blubber.
      In fin whale skin, the delta(15)N values decreased, with no change observed in
      humpback whale skin. Non-linear models generally out-performed linear models and
      the suitability of models varied by species and tissue, indicating the need for
      high model specificity, even among these closely related taxa. CONCLUSIONS: Given
      the poor predictive power of the models to estimate lipid-free delta(13)C values,
      and the unpredictable changes in delta(15)N values due to lipid-extraction, we
      recommend against arithmetical normalization in accounting for lipid effects on
      delta(13)C values for balaenopterid skin or blubber samples. Rather, we recommend
      that duplicate analysis of lipid-extracted (delta(13)C values) and non-treated
      tissues (delta(15)N values) be used.

PMID- 23124666
TI  - Evaluation of electrospray ionisation mass spectrometry as a technique for the
      investigation of competitive interactions: a case study of the ternary Th-Mn-EDTA
      system.
AB  - RATIONALE: Electrospray ionisation mass spectrometry (ESI-MS) is a useful tool
      for exploring the speciation of solution-phase metal complexes; however, the
      quantification of ternary systems is challenging due to the differences in the
      electrospray response of different species. Here, the Th-Mn-EDTA system was
      investigated to evaluate the capability of ESI-MS for quantifying the species
      present. METHODS: Increasingly complex mixtures of Th(IV), Mn(II) and EDTA were
      analysed using manual flow injection of samples into an HPLC grade water mobile
      phase delivered to an ion trap mass spectrometer fitted with an ESI interface
      (ThermoQuest Finnigan Mat LCQ). Mass spectra were obtained in the positive and
      negative ion modes over a mass-to-charge (m/z) range from 50-2000. RESULTS: The
      instrumental response to EDTA was affected by the addition of Th(NO(3))(4) but
      not MnCl(2), while the response to both Th-EDTA and Mn-EDTA species was affected
      by addition of the other metal salt. Internal standards were also found to
      suppress signals to different extents. Therefore, each signal suppression was
      carefully quantified as the solution became more complex, and signal correction
      factors were used in conjunction with regular external calibration. Mixed metal
      signals were quantified adequately. CONCLUSIONS: This study showed the complexity
      of quantifying a ternary system involving different co-existing species.
      Nonetheless, the step-wise protocol developed provided quantitative data on the
      displacement of Mn from its EDTA complex by Th.

PMID- 23124667
TI  - More inclusive or selective ionization for mass spectrometry using obstructive
      sonic spray ionization and voltage polarity switching.
AB  - RATIONALE: A new variation of sonicspray ionization (SSI) significantly enhances
      its sensitivity with an advantage of producing selective or more inclusive
      ionization by changing the polarity of the potential applied to an obstruction in
      the path of the SSI spray. This technique also provides high sensitivity with
      water solutions, which is difficult for electrospray ionization (ESI) without
      added organic solvent. METHODS: An Orbitrap Exactive mass spectrometer with an
      IonMax source heated electrospray ionization (ESI) probe operating at its maximum
      sheath gas setting was used for SSI. Both positive and negative polarities
      varying from 0.1 to 4 kV were applied to a metal obstruction positioned in the
      path of the spray using an atmospheric solid analysis probe. All mass spectra for
      this study were acquired in the positive ion mode. RESULTS: SSI using a variety
      of obstructions improved the observed analyte ion abundance of small molecules,
      peptides, and proteins by approximately two orders of magnitude. The addition of
      a DC or AC voltage to a metal obstruction further enhanced the abundance of
      analyte ions by an additional two orders of magnitude. The relative abundances of
      the detected positive ions were considerably altered by switching the voltage
      polarity on the obstruction. CONCLUSIONS: SSI with an obstruction improves the
      sensitivity of various samples compared with SSI. An applied voltage onto the
      obstruction further enhances the analyte ion abundances to approximately equal
      that of ESI but has the added advantage that switching the voltage polarity from
      positive to negative on the obstruction emphasizes different compounds present in
      the sample.

PMID- 23124668
TI  - Sensitive ionization of non-volatile analytes using protein solutions as spray
      liquid in desorption electrospray ionization mass spectrometry.
AB  - RATIONALE: Desorption electrospray ionization (DESI) is the most popular ambient
      ionization technique for direct analysis of complex samples without sample
      pretreatment. However, for many applications, especially for trace analysis, it
      is of interest to improve the sensitivity of DESI-mass spectrometry (MS).
      METHODS: In traditional DESI-MS, a mixture of methanol/water/acetic acid is
      usually used to generate the primary ions. In this article, dilute protein
      solutions were electrosprayed in the DESI method to create multiply charged
      primary ions for the desorption ionization of trace analytes on various surfaces
      (e.g., filter paper, glass, Al-foil) without any sample pretreatment. The analyte
      ions were then detected and structurally characterized using a LTQ XL mass
      spectrometer. RESULTS: Compared with the methanol/water/acetic acid (49:49:2,
      v/v/v) solution, protein solutions significantly increased the signal levels of
      non-volatile compounds such as benzoic acid, TNT, o-toluidine, peptide and
      insulin in either positive or negative ion detection mode. For all the analytes
      tested, the limits of detection (LODs) were reduced to about half of the original
      values which were obtained using traditional DESI. The results showed that the
      signal enhancement is highly correlated with the molecular weight of the proteins
      and the selected solid surfaces. CONCLUSIONS: The proposed DESI method is a
      universal strategy for rapid and sensitive detection of trace amounts of strongly
      bound and/or non-volatile analytes, including explosives, peptides, and proteins.
      The results indicate that the sensitivity of DESI can be further improved by
      selecting larger proteins and appropriate solid surfaces.

PMID- 23124669
TI  - Improved reporter ion assignment of raw isobaric stable isotope labeled liquid
      chromatography/matrix-assisted laser desorption/ionization tandem time-of-flight
      mass spectral data for quantitative proteomics.
AB  - RATIONALE: Isobaric labeling strategies (e.g. iTRAQ or TMT) are commonly applied
      in tandem mass spectrometric (MS/MS) level quantitative proteomics. However, we
      frequently observed missing isotope reporter ion signals in a large-scale liquid
      chromatography/matrix-assisted laser desorption/ionization tandem time-of-flight
      mass spectrometric (LC/MALDI-TOF/TOF) quantitative proteomics experiment. To
      understand this issue, we systematically investigated the processing of MS/MS
      spectra into peak lists prior to peptide identification and quantification.
      METHODS: A 15-protein standard, with six proteins in different concentrations,
      was labeled with iTRAQ 4-plex, iTRAQ 8-plex or TMT 6-plex, tryptic digested and
      measured using LC/MALDI-TOF/TOF. Three commercially and open-source available
      peak list generation software tools were compared based on missing reporter ions,
      peptide identification and quantification. RESULTS: We found that each tool
      discarded lower-intensity reporter ions, when they followed a higher intensity
      reporter ion, due to the implemented de-isotoping algorithms. By using the non-de
      isotoping setting within TS2Mascot, we found that all reporter ions are exported,
      yet less peptides were identified with Mascot. Therefore, we developed a strategy
      merging the de-isotoped and non-de-isotoped outputs from TS2Mascot using the Perl
      script RICmerge.pl. CONCLUSIONS: With this approach, we correctly quantified all
      labeled peptides that were identified within the 15-protein standard. This
      strategy allows improved annotation of isobaric tag labeled peptide MS/MS spectra
      and improves downstream peptide and protein quantification in proteomics studies.

PMID- 23124670
TI  - Compact two-step laser time-of-flight mass spectrometer for in situ analyses of
      aromatic organics on planetary missions.
AB  - RATIONALE: A miniature time-of-flight mass spectrometer measuring 20 cm in length
      has been adapted to demonstrate two-step laser desorption/ionization (LDI) in a
      compact instrument package for enhanced organics detection. Two-step LDI
      decouples the desorption and ionization processes, relative to traditional LDI,
      in order to produce low-fragmentation mass spectra of organic analytes. Tuning
      the UV ionization laser energy would allow control of the degree of
      fragmentation, which might enable better identification of constituent species.
      METHODS: A reflectron time-of-flight mass spectrometer prototype was modified to
      allow a two-laser configuration, with IR (1064 nm) desorption followed by UV (266
      nm) postionization. A relatively low ion extraction voltage of 5 kV was applied
      at the sample inlet. RESULTS: The instrument capabilities and performance were
      demonstrated with analysis of a model polycyclic aromatic hydrocarbon,
      representing a class of compounds important to the fields of Earth and planetary
      science. Two-step laser mass spectrometry (L2MS) analysis of a model PAH, pyrene,
      was demonstrated, including molecular ion identification and the onset of tunable
      fragmentation as a function of ionizing laser energy. Mass resolution m/Deltam =
      380 at full width at half-maximum was achieved for gas-phase postionization of
      desorbed neutrals in this highly compact mass analyzer. CONCLUSIONS: Achieving
      L2MS in a highly miniaturized instrument enables a powerful approach to the
      detection and characterization of aromatic organics in remote terrestrial and
      planetary applications. Tunable detection of molecular and fragment ions with
      high mass resolution, diagnostic of molecular structure, is possible on such a
      compact L2MS instrument. The selectivity of L2MS against low-mass inorganic salt
      interferences is a key advantage when working with unprocessed, natural samples,
      and a mechanism for the observed selectivity is proposed.

PMID- 23124671
TI  - Nitrogen and triple oxygen isotopes in near-road air samples using chemical
      conversion and thermal decomposition.
AB  - RATIONALE: The determination of triple oxygen (delta(18)O and delta(17)O) and
      nitrogen isotopes (delta(15)N) is important when investigating the sources and
      atmospheric paths of nitrate and nitrite. To fully understand the atmospheric
      contribution into the terrestrial nitrogen cycle, it is crucial to determine the
      delta(15)N values of oxidised and reduced nitrogen species in precipitation and
      dry deposition. METHODS: In an attempt to further develop non-biotic methods and
      avoid expensive modifications of the gas-equilibration system, we have combined
      and modified sample preparation procedures and analytical setups used by other
      researchers. We first chemically converted NO(3)(-) and NH(4)(+) into NO(2)(-)
      and then into N(2)O. Subsequently, the resulting gas was decomposed into N(2) and
      O(2) and analyzed by isotope ratio mass spectrometry (IRMS) using a pre
      concentration system equipped with a gold reduction furnace. RESULTS: The
      delta(17)O, delta(18)O and delta(15)N values of nitrate and nitrite samples were
      acquired simultaneously in one run using a single analytical system. Most
      importantly, the entire spectrum of delta(17)O, delta(18)O and/or delta(15)N
      values was determined from atmospheric nitrate, nitric oxide, ammonia and
      ammonium. The obtained isotopic values for air and precipitation samples were in
      good agreement with those from previous studies. CONCLUSIONS: We have further
      advanced chemical approaches to sample preparation and isotope analyses of
      nitrogen-bearing compounds. The proposed methods are inexpensive and easily
      adaptable to a wide range of laboratory conditions. This will substantially
      contribute to further studies on sources and pathways of nitrate, nitrite and
      ammonium in terrestrial nitrogen cycling.

PMID- 23124672
TI  - Microsynthesis and electron ionization mass spectral studies of O(S)-alkyl N,N
      dimethyl alkylphosphono(thiolo)thionoamidates for Chemical Weapons Convention
      verification.
AB  - RATIONALE: The availability of mass spectra and interpretation skills are
      essential for unambiguous identification of the Chemical Weapons Convention (CWC)
      related chemicals. The O(S)-alkyl N,N-dimethyl
      alkylphosphono(thiolo)thionoamidates are included in the list of scheduled CWC
      related compounds, but there are very few spectra from these compounds in the
      literature. This paper examines these spectra and their mass spectral
      fragmentation routes. METHODS: The title chemicals were prepared through
      microsynthetic protocols and were analyzed using electron ionization mass
      spectrometry with gas chromatography as a MS-inlet system. Structures of
      fragments were confirmed using analysis of fragment ions of deuterated analogs,
      tandem mass spectrometry and density functional theory (DFT) calculations.
      RESULTS: Mass spectrometric studies revealed some interesting fragmentation
      pathways during the ionization process, such as alkene and amine elimination and
      McLafferty-type rearrangements. The most important fragmentation route of the
      chemicals is the thiono-thiolo rearrangement. DFT calculations are used to
      support MS results and to reveal relative preference formation of fragment ions.
      The retention indices (RIs) of all the studied compounds are also reported.
      CONCLUSIONS: Mass spectra of the synthesized compounds were investigated with the
      aim to enrich the Organization for the Prohibition of Chemical Weapons (OPCW)
      Central Analytical Database (OCAD) which may be used for detection and
      identification of CWC-related chemicals during on-site inspection and/or off-site
      analysis such as OPCW proficiency tests.

PMID- 23124675
TI  - Mass spectrometry studies of Lycopodium alkaloid sauroine.

PMID- 23124676
TI  - Investigation on the hydrolysis of the anticancer drug cisplatin by Fourier
      transform ion cyclotron resonance mass spectrometry.

PMID- 23124673
TI  - Identification and separation of protein, contaminant and substrate peaks using
      gentle-secondary ion mass spectrometry and the g-ogram.
AB  - RATIONALE: Secondary ion mass spectrometry (SIMS) is an important technique for
      the characterization of proteins at surfaces. However, interpretation of the mass
      spectra is complicated owing to confusion with peaks from contaminants and the
      substrate which is further compounded by complex fragmentation mechanisms. We
      test a new development of the G-SIMS method called the g-ogram to separate out
      spectral components without a priori information about which peaks to include in
      the analysis and which peaks relate to each component. METHODS: The effectiveness
      of the g-ogram method is investigated using a model system of lysozyme adsorbed
      onto a silicon wafer and indium tin oxide substrates. In the method, two SIMS
      spectra are acquired using Bi(+) and Mn(+) primary ions which create lower and
      higher fragmentation in the spectra, respectively. The g-ogram separates out
      components using a separation parameter that is related to the fragmentation
      energy. RESULTS: The g-ogram separates the spectrum of lysozyme adsorbed onto a
      silicon wafer into three components: (i) the substrate and PDMS contamination;
      (ii) a second, but unexpected, contaminant; and (iii) peaks from the protein
      amino acids. Similar results are achieved for the indium tin oxide substrate. In
      addition, evidence of fragments from plural amino acids with two candidate peaks
      at 140.12 Da and 185.08 Da is observed. CONCLUSIONS: The g-ogram method
      effectively separates out mass peaks relating to the substrate, contamination and
      protein without any a priori information or subjective decisions about which
      peaks to include in the analysis (so called 'peak picking'). This is a great help
      to analysts. We find two possible peaks from plural amino acids but no evidence
      of pluralities is found for peaks above 240 Da that are generated from when using
      Bi or Mn primary ions.

PMID- 23124674
TI  - Electrospray ionization mass spectrometric observation of the interaction between
      cesium ions and amino acids.

PMID- 23124679
TI  - A case of alpha-synuclein gene duplication presenting with head-shaking
      movements.
AB  - BACKGROUND: PARK4 is a candidate locus for familial Parkinson's disease (PD),
      combined with multiplication of the alpha-synuclein gene (SNCA). The eventual
      phenotype is dependent on the copy number of SNCA. Mutations in leucine-rich
      repeat kinase 2 (LRRK2) are also causative of parkinsonism. This report describes
      a man who presented at our hospital complaining of a stagger after running and
      difficulty in handling the mouse of a personal computer, having suffered tremors
      since his twenties. Nine months after treatment and discharge, he developed
      titubation and began to drag his right foot. METHODS: We examined the patient's
      family pedigree for SNCA dosage, using quantitative polymerase chain reaction. We
      also screened this pedigree for mutations in parkin and LRRK2, using gene
      sequencing techniques. RESULTS: We identified the proband, his sister, and his
      paternal uncle as carrying a duplication of SNCA. In addition, we found that the
      proband and his mother carried the G2385R variant of the LRRK2, a strong risk
      factor for PD in Asians and the rare V1450I variant, although only the proband
      showed symptoms of parkinsonism. No mutations were found in parkin. CONCLUSIONS:
      The combination of SNCA gene duplication and LRRK2 G2385R variant may explain the
      early onset of disease in this patient.

PMID- 23124678
TI  - Comparison of the feasibility of laparoscopic resection of the primary tumor in
      patients with stage IV colon cancer with early and advanced disease: the short-
      and long-term outcomes at a single institution.
AB  - PURPOSE: The role of resection of the primary tumor in patients with stage IV
      colorectal cancer (CRC) remains controversial. Laparoscopic resection has become
      an accepted therapeutic option for treating early stage I-III CRC; however, it
      has not been evaluated for use in patients with advanced stage disease. METHODS:
      We conducted a retrospective observational study to evaluate the feasibility of
      laparoscopic resection of the primary tumor exclusively in patients with stage IV
      colon cancer compared to open resection in patients with stage IV colon cancer
      and laparoscopic resection in patients with stage I-III colon cancer in terms of
      operative results and short- and long-term outcomes. RESULTS: Laparoscopic
      resection was performed in 35 stage IV patients and open resection was performed
      in 40 stage IV patients. One hundred and eighteen stage I-III patients who
      underwent laparoscopic resection were evaluated. In the comparison between the
      laparoscopic group and the open group among patients with stage IV colon cancer,
      postoperative recovery appeared to be better in the laparoscopic group than in
      the open group, as reflected by shorter times to resumption of a regular diet (p
      = 0.049), shorter lengths of hospitalization (p = 0.083), increased feasibility
      of postoperative chemotherapy (p < 0.001), shorter time intervals from surgery to
      chemotherapy (p = 0.031) and longer median survival (p = 0.078) at the expense of
      longer operative times (p = 0.025). In the comparison between the laparoscopic
      resection in stage IV and stage I-III disease groups, no significant differences
      were observed in operative results and short- and long-term outcomes, except for
      the rate of ostomy creation (48.5 vs. 8.5%, p = 0.02). CONCLUSION: Laparoscopic
      resection of the primary tumor in patients with stage IV colon cancer achieves
      equivalent results to that performed in patients with stage I-III disease and
      that performed in patients with stage IV disease using open resection. The use of
      a minimally invasive approach in the laparoscopic procedure is beneficial because
      it results in shorter times to resumption of a normal diet, shorter lengths of
      hospitalization, increased feasibility of postoperative chemotherapy and shorter
      time intervals from surgery to chemotherapy at the expense of longer operative
      times. We believe that patients undergoing laparoscopic resection can receive
      targeted chemotherapy earlier and more aggressively, which might provide a
      survival benefit.

PMID- 23124684
TI  - A test of the occupational matching hypothesis for rehabilitation clients with
      severe mental illness.
AB  - PURPOSE: This study compared job matching rates for clients with severe mental
      illness enrolled in two types of employment programs. Also examined was the
      occupational matching hypothesis that job matching is associated with better
      employment outcomes. METHODS: The study involved a secondary analysis of a
      randomized controlled trial comparing evidence-based supported employment to a
      diversified placement approach. The study sample consisted of 187 participants,
      of whom 147 obtained a paid job during the 2-year follow-up. Jobs were coded
      using the Dictionary of Occupational Titles classification system. Match between
      initial job preferences and type of job obtained was the predictor variable.
      Outcomes included time to job start, job satisfaction, and job tenure on first
      job. RESULTS: Most occupational preferences were for clerical and service jobs,
      and most participants obtained employment in these two occupational domains. In
      most cases, the first job obtained matched a participant's occupational
      preference. The occupational matching hypothesis was not supported for any
      employment outcome. The occupational matching rate was similar in this study to
      previous studies. CONCLUSIONS: Most clients who obtain employment with the help
      of evidence-based supported employment or diversified placement services find
      jobs matching their occupational preference, and most often it is a rough match.
      Occupational matching is but one aspect of job matching; it may be time to
      discard actuarial classification systems such as the Dictionary of Occupational
      Titles as a basis for assessing job match.

PMID- 23124682
TI  - Role of MR imaging in laryngoscleroma.
AB  - To evaluate the role of MR imaging in patients with laryngoscleroma. We
      retrospectively reviewed the MR imaging of 14 patients (11 female, 3 male with
      mean age of 31 years) with pathologically proven laryngoscleroma. They presented
      with dysphonia (n = 12), stridor (n = 8) and airway obstruction (n = 4). They
      underwent T1- and T2-weighted MR images and post contrast study after injection
      of 0.1 mmol Gd/DTPA. Laryngoscleroma was seen in the subglottic (n = 13) and
      supraglottic (n = 1) regions. Laryngoscleroma at granulomatous stage (n = 6)
      appeared as diffuse circumferential soft tissue mass with high (n = 4) or mixed
      (n = 2) signal intensity on T2-weighted images with homogenous (n = 4) and
      inhomogeneous (n = 2) pattern of contrast enhancement. At fibrotic stage (n = 8),
      laryngoscleroma was seen as diffuse asymmetrical circumferential thickening of
      the subglottic region with low signal intensity on T2-weighted images and mild
      contrast enhancement. Subglottic lesions encircled the subglottic region with
      marked (n = 5) and mild (n = 9) narrowing of the airway with variable degree of
      extension into the trachea in three patients. There was diffuse thickening of the
      epiglottis, aryepiglottic folds in one patient with supraglottic scleroma. MR
      imaging is a non-invasive imaging modality for accurate localization, extension
      and staging of laryngoscleroma. These data is important for treatment planning.

PMID- 23124683
TI  - Internal validation of models with several interventions.
AB  - In cost-effectiveness analyses, models are used typically to synthesize the best
      available data and/or extrapolate beyond clinical trial data. Ideally, models
      should be validated both internally and externally. The purpose of this paper is
      to suggest a test for internal validation of models where several interventions
      for the same clinical indication are compared. To the best of our knowledge, such
      a specific test does not yet exist. There are four versions of the test, which
      consider the relationship between incremental downstream costs and effects in the
      case of a single or several endpoints. We apply two versions of the validation
      test to published cost-effectiveness analyses of physical activity programs and
      demonstrate internal validity of the model in one study and lack of internal
      validity of the model in the other study. 

PMID- 23124677
TI  - Cadmium chelation by frustulins: a novel metal tolerance mechanism in Nitzschia
      palea (Kutzing) W. Smith.
AB  - The ubiquity of diatom distribution, species richness, short generation time, and
      specific sensitivity to several environmental stressors such as metals, make
      diatoms particularly useful for scientific studies. Anthropogenic activities have
      increased the concentration of metals in air, soil and water. Due to their
      toxicity and persistent character, the effects of metals on organisms have been
      extensively studied. In this work, the association of cadmium to different
      extracellular molecules of Nitzschia palea cells was investigated. Cells were
      grown in the absence and presence (0.2 mg l(-1)) of cadmium in Chu no. 10 medium.
      Extracellular polysaccharides were extracted, and subsamples were used for
      polysaccharide and Cd determination. The frustules were broken mechanically under
      liquid nitrogen and the intracellular and frustule fractions separated.
      Frustulins, a protein family found on the outmost frustule layer, constituting a
      protection coating to environmental stress, were extracted. In each fraction
      proteins were quantified by the BCA method and separated by gel electrophoresis
      (SDS-PAGE). Cadmium associated to each fraction was quantified by Inductively
      Coupled Plasma Mass Spectrometry (ICP-MS) analysis. Exposure of Nitzschia palea
      to cadmium decreased extracellular polysaccharides by 52.8 % and increased 6
      times the amount of frustulins. Cadmium was mostly retained extracellularly: 85.4
      % was bound to the frustulin fraction, and 11.1 % to polysaccharides. The ability
      of Nitzschia palea to increase the production of frustulins due to the presence
      of Cd, the extracellular location of this frustulin coating and the ability of
      these proteins to bind Cd, suggests a new cellular defense mechanism to metals
      unknown until now.

PMID- 23124681
TI  - Activity and coexpression of Drosophila black with ebony in fly optic lobes
      reveals putative cooperative tasks in vision that evade electroretinographic
      detection.
AB  - Drosophila mutants black and ebony show pigmentation defects in the adult
      cuticle, which disclose their cooperative activity in beta-alanyl-dopamine
      formation. In visual signal transduction, Ebony conjugates beta-alanine to
      histamine, forming beta-alanyl-histamine or carcinine. Mutation of ebony disrupts
      signal transduction and reveals an electroretinogram (ERG) phenotype. In contrast
      to the corresponding cuticle phenotype of black and ebony, there is no ERG
      phenotype observed when black expression is disrupted. This discrepancy calls
      into question the longstanding assumption of Black and Ebony interaction. The
      purpose of this study was to investigate the role of Black and Ebony in fly optic
      lobes. We excluded a presynaptic histamine uptake pathway and confirmed histamine
      recycling via carcinine formation in glia. beta-Alanine supply for this pathway
      is independent of enzymatic synthesis by Black and beta-alanine synthase Pyd3.
      Two versions of Black are expressed in vivo. Black is a specific aspartate
      decarboxylase with no activity on glutamate. RNA in situ hybridization and anti
      Black antisera localized Black expression in the head. Immunolabeling revealed
      expression in lamina glia, in large medulla glia, in glia of the ocellar
      ganglion, and in astrocyte-like glia below the ocellar ganglion. In these glia
      types, Black expression is strictly accompanied by Ebony expression. Activity,
      localization, and strict coexpression with Ebony strongly indicate a specific
      mode of functional interaction that, however, evades ERG detection.

PMID- 23124685
TI  - Return to work perceptions and actual return to work in workers with common
      mental disorders.
AB  - INTRODUCTION: Return to work (RTW) perceptions have been found to predict actual
      RTW of workers with common mental disorders. This study aims to (1) assess the
      relative value of RTW self-efficacy (RTW-SE) and RTW expectation in predicting
      actual RTW and (2) explore the role of mental health symptoms, work
      characteristics and their interaction as determinants of these RTW perceptions at
      baseline and over time. METHODS: Workers (N = 179) with common mental disorders
      were included at the start of their sick leave and followed-up at 3, 6, 9, and 12
      months. RTW self-efficacy, RTW expectation, mental health and RTW were assessed
      by self-report. Kaplan-Meier survival analysis was used to test the predictive
      value of RTW-SE and RTW expectation against the actual RTW. Linear regression was
      used to study the associations of mental health symptoms, work characteristics
      and their interaction with RTW-SE at baseline. Mental health symptoms in relation
      to RTW-SE over the first 6 months were analyzed using Linear Mixed Models.
      RESULTS: Compared to RTW expectation, differences in RTW-SE were more predictive
      of actual RTW. At baseline, lower fatigue, depressive symptoms, and work pace-
      and load were associated with higher RTW-SE. Decreasing levels of fatigue and
      depressive symptoms over time were associated with parallel improvements in RTW
      SE. Workers with high work pace and workload at baseline showed lower levels of
      RTW-SE at all time points. CONCLUSIONS: We recommend the use of the RTW-SE scale
      to detect workers with common mental disorders at risk of a late RTW. Work
      characteristics and changes in mental health symptoms were associated with RTW-SE
      over time.

PMID- 23124680
TI  - Alpha2-antiplasmin regulates the development of dermal fibrosis in mice by
      prostaglandin F(2alpha)  synthesis through adipose triglyceride lipase/calcium
      independent phospholipase A(2).
AB  - OBJECTIVE: Systemic sclerosis (SSc) is characterized by fibrosis of the skin and
      visceral organs. Patients with SSc have enhanced plasma levels of the plasmin
      alpha2-antiplasmin (alpha2AP) complex, and we recently implicated alpha2AP in the
      development of fibrosis through transforming growth factor beta (TGFbeta)
      production. This study was undertaken to clarify how alpha2AP induces TGFbeta
      production and the development of fibrosis. METHODS: To clarify the detailed
      mechanism by which alpha2AP induces TGFbeta production, we focused on adipose
      triglyceride lipase (ATGL)/calcium-independent phospholipase A(2) (iPLA(2)) and
      examined whether ATGL/ iPLA(2) is associated with alpha2AP-induced TGFbeta
      production. The mouse model of bleomycin-induced SSc was used to evaluate the
      role of alpha2AP in the development of fibrosis. Dermal thickness and collagen
      content were determined in mouse skin treated with phosphate buffered saline or
      bleomycin. Moreover, we cultured SSc-like fibroblasts from the bleomycin-treated
      mouse skin and examined the production of TGFbeta and prostaglandin F(2alpha)
      (PGF(2alpha)). RESULTS: We found that alpha2AP binding to ATGL promoted
      PGF(2alpha) synthesis through iPLA(2) in fibroblasts, and the PGF(2alpha)
      synthesis that was promoted by alpha2AP induced TGFbeta production in
      fibroblasts. In addition, the neutralization of alpha2AP attenuated the
      production of TGFbeta and PGF(2alpha) in SSc-like fibroblasts from mice. The
      alpha2AP deficiency attenuated bleomycin-induced fibrosis and PGF(2alpha)
      synthesis, while the administration of PGF(2alpha) to alpha2AP-deficient mice
      facilitated alpha2AP deficiency-attenuated fibrosis. CONCLUSION: These findings
      suggest that alpha2AP regulates the development of fibrosis by PGF(2alpha)
      synthesis through ATGL/iPLA(2). The inhibition of alpha2AP-initiated pathways
      might provide a novel therapeutic approach to fibrotic diseases.

PMID- 23124687
TI  - Sacral nerve stimulation for constipation.
AB  - BACKGROUND: For over 10 years sacral nerve stimulation (SNS) has been used for
      patients with constipation resistant to conservative treatment. A review of the
      literature is presented. METHODS: PubMed, MEDLINE and Embase databases were
      searched for studies demonstrating the use of SNS for the treatment of
      constipation. RESULTS: Thirteen studies have been published describing the
      results of SNS for chronic constipation. Of these, three were in children and ten
      in adults. Test stimulation was successful in 42-100 per cent of patients. In
      those who proceeded to permanent SNS, up to 87 per cent showed an improvement in
      symptoms at a median follow-up of 28 months. The success of stimulation varied
      depending on the outcome measure being used. Symptom improvement correlated with
      improvement in quality of life and patient satisfaction scores. CONCLUSION: SNS
      appears to be an effective treatment for constipation, but this needs to be
      confirmed in larger prospective studies with longer follow-up. Improved outcome
      measures need to be adopted given the multiple symptoms that constipation may be
      associated with. Comparison with other established surgical therapies also needs
      consideration.

PMID- 23124686
TI  - Obstacles to and facilitators of return to work after work-disabling back pain:
      the workers' perspective.
AB  - INTRODUCTION: Back pain entails considerable costs, particularly because many
      injured workers are absent from work for long periods. Factors that influence
      return to work among workers with back pain are still, however, not well
      understood. This qualitative study aimed at documenting affected workers'
      perspective on the: 1--difficulties caused by back pain, and 2--most important
      obstacles to and facilitators of return to work. METHODS: Two focus groups
      composed of workers having suffered from work-disabling back pain were held: a
      group of participants who had returned to work (n = 9) and a group of
      participants who had not returned or had recently returned to work (n = 10). The
      verbatim accounts of the discussions were transcribed and a content analysis was
      carried out that included a ranking of items. RESULTS: Difficulties caused by
      back pain were related to: (1) personal, (2) family, (3) social, (4)
      occupational, and (5) financial factors, and (6) health services. Obstacles to
      and facilitators of return to work were of 4 different types: (1) occupational
      factors, (2) factors associated with the utilization of health services, (3)
      clinical, and (4) personal factors. Persistent pain, lack of access to
      information or support groups, and lack of collaboration and understanding from
      employer were the most important obstacles identified, whereas knowledge of one's
      limits and physical training were perceived to be the most important facilitators
      of return to work, ahead of work-related factors. Differences between groups'
      perceptions were attributed mainly to control beliefs. CONCLUSIONS: Personal,
      clinical, occupational and health services factors are perceived by workers with
      back pain to play a crucial role in determining whether they return to work or
      not.

PMID- 23124688
TI  - Analytical approach to determine biogenic amines in urine using microextraction
      in packed syringe and liquid chromatography coupled to electrochemical detection.
AB  - The goal of this work was to develop and validate an analytical method for the
      detection and quantification of the biogenic amines serotonin (5-HT), dopamine
      (DA) and norepinephrine (NE), using microextraction in packed syringe (MEPS) and
      liquid chromatography coupled to electrochemical detection (HPLC-ED) in urine.
      The method was validated according to internationally accepted guidelines from
      the Food and Drug Administration. Linearity was established between 50 and 1000
      ng/mL for 5-HT and between 5 and 1000 ng/mL for DA and NE, with determination
      coefficients (R(2)) >0.99 for all compounds. The limits of quantification and
      detection were respectively 50 and 20 ng/mL for 5-HT, and 5 and 2 ng/mL for DA
      and NE. Within- and between-run precision ranged from 0.84 to 9.41%, while
      accuracy ranged from 0.79 to 12.76% for all compounds. The intermediate precision
      and accuracy were 1.50-8.36 and 0.54-13.51%, respectively. The method was found
      suitable for clinical routine analysis of the studied compounds, using a sample
      volume of 0.5 mL. This is the first study employing a commercially available MEPS
      column for the simultaneous detection and quantification of 5-HT, DA and NE in
      urine by coulometric detection.

PMID- 23124689
TI  - Tandem Bronsted acid promoted and Nazarov carbocyclizations of enyne acetals to
      hydroazulenones.

PMID- 23124691
TI  - Prenatal sonographic findings of duodenal duplication: case report.
AB  - We report a rare case of duodenal duplication cyst that was suspected prenatally.
      Routine prenatal sonography (US) at 19 weeks' gestation showed an abdominal
      cystic mass on the left side of the abdomen. Follow-up US examinations showed a
      partial "double-wall" sign, highly suggestive of enteric duplication, and changes
      in cyst size and wall thickness. Postnatal US examination suggested enteric
      duplication cyst. A laparotomy revealed a duodenal cyst that was completely
      resected. The antenatal US findings associated with this condition, the accuracy
      of its antenatal diagnosis, and its differential diagnosis are discussed.

PMID- 23124690
TI  - Three-dimensional surface deformation-based shape analysis of hippocampus and
      caudate nucleus in children with fetal alcohol spectrum disorders.
AB  - Surface deformation-based analysis was used to assess local shape variations in
      the hippocampi and caudate nuclei of children with fetal alcohol spectrum
      disorders. High-resolution structural magnetic resonance imaging images were
      acquired for 31 children (19 controls and 12 children diagnosed with fetal
      alcohol syndrome/partial FAS). Hippocampi and caudate nuclei were manually
      segmented, and surface meshes were reconstructed. An iterative closest point
      algorithm was used to register the template of one control subject to all other
      shapes in order to capture the true geometry of the shape with a fixed number of
      landmark points. A point distribution model was used to quantify the shape
      variations in terms of a change in co-ordinate positions. Using the localized
      Hotelling T(2) method, regions of significant shape variations between the
      control and exposed subjects were identified and mapped onto the mean shapes.
      Binary masks of hippocampi and caudate nuclei were generated from the segmented
      volumes of each brain. These were used to compute the volumes and for further
      statistical analysis. The Mann-Whitney test was performed to predict volume
      differences between the groups. Although the exposed and control subjects did not
      differ significantly in their volumes, the shape analysis showed the hippocampus
      to be more deformed at the head and tail regions in the alcohol-exposed children.
      Between-group differences in caudate nucleus morphology were dispersed across the
      tail and head regions. Correlation analysis showed associations between the
      degree of compression and the level of alcohol exposure. These findings
      demonstrate that shape analysis using three-dimensional surface measures is
      sensitive to fetal alcohol exposure and provides additional information than
      volumetric measures alone.

PMID- 23124692
TI  - Lack of effect of concomitant stage II cystocele repair on lower urinary tract
      symptoms and surgical outcome after tension-free vaginal tape procedure:
      randomized controlled trial.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of this study was to compare the lower
      urinary tract symptom changes and surgical outcome between the tension-free
      vaginal tape (TVT) procedure with and without concomitant stage II pelvic organ
      prolapse (cystocele) repair in a randomized clinical trial setting. METHODS:
      Patients with urodynamically proven stress urinary incontinence (SUI) and
      asymptomatic stage II cystocele were randomly and equally allocated to either a
      TVT and concomitant cystocele repair group or TVT only group. SUI was corrected
      with TVT in all cases. The cystocele repair procedure was performed with
      Gynemesh. Lower urinary tract symptoms and surgical outcome were assessed at
      postoperative year 1. Lower urinary tract symptoms were assessed with the
      American Urological Association Symptom Score (AUASS) questionnaire,
      uroflowmetry, and postvoid residual (PVR). RESULTS: The cure rate of TVT only and
      the concomitant repair group was 87 and 91%, respectively (p > 0.05). Cystocele
      was cured in all patients in the concomitant repair group. After the operation,
      the total AUASS were 6.4 and 8.4 in the TVT only group and concomitant repair
      group, respectively, with no statistical difference. There was no difference in
      the change in peak flow rate (Qmax) and PVR between the two groups. The
      prevalence of postoperative mixed incontinence was not different between the two
      groups. CONCLUSIONS: In patients with stage II cystocele and SUI, there was no
      difference in the surgical outcome and lower urinary tract symptoms between the
      TVT sling only group and concomitant repair group. Cystocele repair can be safely
      omitted in patients with stage II cystocele.

PMID- 23124693
TI  - Elevated serum high-sensitivity C-reactive protein levels in fibromyalgia
      syndrome patients correlate with body mass index, interleukin-6, interleukin-8,
      erythrocyte sedimentation rate.
AB  - The levels of several inflammatory cytokines are abnormal in many patients with
      the fibromyalgia syndrome (FMS) and may play a role in its pathogenesis. The
      inflammatory marker C-reactive protein (CRP) is associated with the disease
      activity in patients with inflammatory rheumatic diseases, but its role in FMS is
      unknown. We undertook this study to determine whether high-sensitivity CRP
      (hsCRP) is elevated in FMS and whether its levels relate to key biologic or
      clinical measures. One hundred and five patients with FMS (1990 ACR criteria) and
      61 healthy normal controls (HNC) at a ratio of 2:1 were recruited. The serum
      concentrations of hsCRP, interleukin-8 (IL-8), and interleukin-6 (IL-6) were
      assessed using enzyme-linked immunosorbent assays. The hsCRP levels were
      marginally higher in FMS than in HNC (p = 0.06) and its abnormality rate (>1.5 SD
      above the HNC mean) was significantly higher in FMS (25 %) compared with HNC (6.8
      %) (p = 0.03). Serum IL-8 levels, IL-6 levels, and erythrocyte sedimentation rate
      (ESR) in FMS did not differ from those in HNC. Body mass index (BMI), ESR, IL-8,
      and IL-6 levels correlated with hsCRP levels in FMS. No associations were found
      between hsCRP and age, gender, ethnicity, or other clinical measures. Serum CRP
      levels were higher in FMS and significantly correlated with BMI, ESR, IL-8, and
      IL-6 levels, suggesting that inflammation may contribute to the symptoms in some
      FMS patients, particularly those who are obese. Weight loss and therapies
      directed against inflammation may be useful in the management of FMS patients
      with elevated hsCRP.

PMID- 23124694
TI  - Association of suboptimal 25-hydroxyvitamin D levels with knee osteoarthritis
      incidence in post-menopausal Egyptian women.
AB  - The main aim of this study was to assess the vitamin D status of newly diagnosed
      knee osteoarthritis (OA) patients. Thirty-six post-menopausal Egyptian females of
      mean age 54.7 years with knee OA were recruited alongside ten healthy males of
      mean age 25.8 years. The body mass index of all knee OA patients was calculated,
      and full patient history was gathered to screen for vitamin D status altering
      conditions or medication. Total 25-hydroxyvitamin D [25(OH)D] was assessed using
      HPLC which permitted an individualized assessment of both forms of the vitamin's
      metabolite, 25(OH)D2 and 25(OH)D3. Results showed that mean 25(OH)D +/- SEM
      concentrations were 25.0 +/- 1.6 ng/mL and 35.4 +/- 2.1 ng/mL for female patients
      and healthy male participants, respectively. Student's t test statistical
      comparison yielded a significant result (P = 0.001) when comparing healthy and
      osteoarthritic participants, and insignificant results when comparing patients of
      different BMI class, and the different forms of the vitamin's metabolite (P =
      0.184 and 0.335, respectively). The 95 % confidence interval associated with knee
      OA incidence is 21.9-28.1 ng/mL, which is in the vitamin D insufficiency zone. In
      Conclusion, suboptimal 25(OH)D levels are associated with knee OA incidence in
      post-menopausal Egyptian females which further fortifies accumulating evidence.

PMID- 23124695
TI  - Complicated brucellar spondylodiscitis: experience from an endemic area.
AB  - The demographical, clinical, and therapeutical features of patients with
      brucellar spondylodiscitis (BS) were evaluated in this study. Of the 96 patients
      with brucellosis, 20 (20.8%) were diagnosed with spondylodiscitis. Patients who
      had BS were more likely to be older (p = 0.001), have higher erythrocyte
      sedimentation rates (p = 0.01), and more likely to be anemic (p = 0.017). Lumbar
      segment (18/20) was frequently involved region. BS was complicated with
      paravertebral or epidural abscess in seven, radiculitis in six, and psoas abscess
      in five of cases. Antibiotic regimens including two or three antibiotics with
      combination of doxycycline, rifampin, and streptomycin were used. In this series,
      the mean duration of antimicrobial therapy was 18 weeks (range 12-56 weeks).
      Attention is drawn to this disease given the need for prolonged duration of
      treatment especially in complicated cases in order to avoid possible sequelae.

PMID- 23124696
TI  - Sexuality of men with fibromyalgia: what are the factors that cause sexual
      dysfunction?
AB  - The purpose of the present study is to compare male patients with the
      fibromyalgia syndrome (FMS) with healthy individuals in terms of the sexual
      function. For the purposes of this study, 37 sexually active male FMS patients
      and 30 healthy controls were enrolled. The demographic data of the patients were
      recorded, and the widespread pain observed in FMS was graded with the help of the
      visual analogue scale (VAS 0-100 mm). Sexual function was assessed according to
      the international index of erectile function (IIEF) scoring system. The disease
      related quality of life was measured with the help of the Short Form-36 quality
      of life questionnaire (SF-36 QoL). Levels of anxiety and depression observed in
      the patients were graded through the Hospital Anxiety and Depression Scale
      (HADS). Patients with FMS had significantly lower scores in each of the five
      domains of the IIEF in comparison with the healthy control group (p < 0.001).
      Patients' age and widespread pain were negatively correlated with the IIEF scores
      (p < 0.05). The SF-36 scores (physical functioning, role limitations due to
      physical problems, pain and general health perception) were observed to be
      positively correlated with the IIEF scores (p < 0.05). No significant
      relationship has been observed between the scores obtained from the domains of
      IIEF and the psychological status (p > 0.05). FMS leads to an impairment in the
      sexual function in male patients, which is especially strongly associated with
      the age, widespread pain and the quality of life.

PMID- 23124697
TI  - Authorship problems in scholarly journals: considerations for authors, peer
      reviewers and editors.
AB  - Authorship problems in scholarly journals shake the foundations of research,
      diminish scientific quality of papers and devalue records of citation tracking
      services. The 'Publish or Perish' mantra is thought to drive some instances of
      unfair, honorary authorship, particularly in countries of emerging scientific
      power. Though causes of honorary, gift, guest and ghost authorship are still ill
      defined, it is possible to avoid some of these instances by improving awareness
      of what constitutes authorship and by adhering to the editorial policies of
      learned associations. This paper overviews common cases of inappropriate
      authorship and suggests options to solve related problems by authors, reviewers
      and editors of scholarly journals.

PMID- 23124699
TI  - Sensitivity of early life stages of white sturgeon, rainbow trout, and fathead
      minnow to copper.
AB  - Populations of white sturgeon (WS; Acipenser transmontanus) are in decline in
      several parts of the United States and Canada, attributed primarily to poor
      recruitment caused by degradation of habitats, including pollution with
      contaminants such as metals. Little is known about sensitivity of WS to
      contaminants or metals such as copper (Cu). Here, acute (96 h) mortalities of WS
      early life stages due to exposure to Cu under laboratory conditions are reported.
      Two standard test species, rainbow trout (Oncorhynchus mykiss) and fathead minnow
      (Pimephales promelas), were exposed in parallel to determine relative sensitivity
      among species. Swim-up larvae [15 days post-hatch (dph)] and early juveniles (40
      45 dph) of WS were more sensitive to Cu (LC(50) = 10 and 9-17 MUg/L,
      respectively) than were yolksac larvae (8 dph; LC(50) = 22 MUg/L) and the later
      juvenile life stage (100 dph; LC(50) = 54 MUg/L). WS were more sensitive to Cu
      than rainbow trout and fathead minnow at all comparable life stages tested.
      Yolksac larvae of rainbow trout and fathead minnow were 1.8 and 4.6 times,
      respectively, more tolerant than WS, while swim-up and juvenile life stages of
      rainbow trout were between 1.4- and 2.4-times more tolerant than WS. When plotted
      in a species sensitivity distribution with other fishes, the mean acute toxicity
      value for early life stage WS was ranked between the 1st and 2nd centile. The WS
      life stage of greatest Cu sensitivity coincides with the beginning of active
      feeding and close association with sediment, possibly increasing risk. WS early
      life stages are sensitive to aqueous copper exposure and site-specific water
      quality guidelines and criteria should be evaluated closely to ensure adequate
      protection.

PMID- 23124698
TI  - Fetal head-symphysis distance: a simple and reliable ultrasound index of fetal
      head station in labor.
AB  - OBJECTIVES: To assess the reproducibility of measurement of a new sonographic
      index of fetal head station in labor, the fetal head-symphysis distance (HSD),
      using three-dimensional ultrasound, and its correlation with digital assessment
      of fetal head descent and with the angle of progression (AoP). METHODS: Three
      dimensional (3D) ultrasound volumes were acquired from 47 nulliparous women in
      active labor following assessment of fetal head station with digital examination.
      The HSD (the distance between the lower edge of the pubic symphysis and the
      nearest point of the fetal skull) was measured independently by two operators in
      order to evaluate intra- and interobserver reproducibility. The correlation
      between HSD, AoP and fetal head station was evaluated using regression analysis.
      Using 3D tomographic ultrasound imaging (TUI), measurements of the HSD were
      obtained in different parasagittal planes to evaluate the influence of inaccurate
      alignment of the probe with the midline of the pelvis. RESULTS: Measurement of
      HSD showed high intraobserver (intraclass correlation coefficient (ICC) = 0.995;
      95% CI, 0.991-0.997) and interobserver (ICC = 0.991; 95% CI, 0.984-0.995)
      reliability. In addition, a high correlation was demonstrated between mid
      sagittal and parasagittal HSD measurements. HSD showed significant negative
      correlation with both fetal head station and AoP. CONCLUSION: Fetal HSD is a
      simple and reliable method for the assessment of fetal head descent in labor.

PMID- 23124700
TI  - Sexing mammalian sperm - Where do we go from here?
AB  - The only commercially viable method of sexing mammalian sperm is to use a flow
      cytometer to measure sperm DNA content via fluorescence of the DNA-bound
      fluorophore Hoechst 33342, and then sort sperm into three populations, probably
      X, probably Y, and undetermined. Millions of insemination doses of sexed sperm
      are produced annually by this procedure. Although accuracy of sexing usually
      exceeds 90%, this procedure of sexing one sperm at a time has serious
      limitations, including cost, sort rates, and damage to sperm resulting in lowered
      fertility, but not abnormalities in offspring. Suggested areas for research
      include determining how sperm are damaged and where in the process of
      fertilization and embryonic development the infertility is manifest. Pre and post
      sorting procedures are done in approximately hourly batches, and these might be
      changed to continuous procedures. Numerous genetic, physical, and immunological
      procedures for sexing millions of sperm in parallel have been proposed, but none
      appears to be suitable for commercialization at this time due to issues of
      accuracy, repeatability, damage to sperm, and other problems. However, increasing
      numbers of reports are appearing concerning improvements in these procedures, and
      it appears inevitable that one or more of them eventually will prove to be
      efficacious. In developing such procedures, it is critical to monitor sexing
      accuracy regularly by rapid and inexpensive procedures such as fluorescence in
      situ hybridization, quantitative PCR, or sort reanalysis by flow cytometry.
      Furthermore, monitoring fertility of sexed sperm such as in vitro fertilization
      should be integral to the development process. Intellectual property issues could
      be substantive.

PMID- 23124701
TI  - The release of EGF domain from EGF-like factors by a specific cleavage enzyme
      activates the EGFR-MAPK3/1 pathway in both granulosa cells and cumulus cells
      during the ovulation process.
AB  - In mammalian preovulatory follicles, LH stimulation induces the ovulation
      process, including follicular wall rupture, granulosa cell luteinization, cumulus
      cell expansion and meiotic maturation of the oocyte. The receptor for LH (LHCGR)
      is expressed mostly in granulosa cells of preovulatory follicles, and is rarely
      expressed in cumulus cells or oocytes. The expression level in granulosa cells
      dramatically decreases after ovulation stimuli. Thus, a potent factor(s) secreted
      by granulosa cells is required to stimulate not only granulosa cells via an
      autocrine manner but also cumulus cells and/or oocytes via a paracrine pathway.
      Recent reports showed that granulosa cells and cumulus cells express EGF-like
      factors that activate the EGF receptor (EGFR)-mitogen-activated protein kinase3/1
      (MAPK3/1) (also known as extracellular signal-regulated kinase1/2 (ERK1/2))
      pathway in both cell types. EGF-like factors are composed of a signal sequence,
      transmembrane domain and EGF domain, suggesting that release of the EGF domain by
      a specific enzyme is essential for interaction with the EGFR to induce the
      ovulation process. In our studies, TACE/ADAM17, which is known to be a
      proteolytic enzyme of EGF-like factors in many types of tissue, was found to be
      expressed in FSH/LH-stimulated granulosa cells and cumulus cells together with
      activation of the EGFR-MAPK3/1 pathway. When TACE/ADAM17 activity was decreased
      by a specific inhibitor or siRNA technique, granulosa cell luteinization, cumulus
      expansion and oocyte maturation were suppressed in an in vitro culture. Thus,
      TACE/ADAM17 is one of the key genes expressed in both granulosa cells and cumulus
      cells for induction of the ovulation process.

PMID- 23124702
TI  - Physically active vs. inactive lifestyle, muscle properties, and glucose
      homeostasis in middle-aged and older twins.
AB  - Exercise-induced positive changes in skeletal muscle properties and metabolism
      decrease the risk for disability, cardiometabolic diseases and mortality. Here,
      we studied muscle properties and glucose homeostasis in a non-exercise stage in
      twin pairs with co-twins discordant for physical activity habits for at least 32
      years of their adult lives. Isometric knee extension force, MR imaging of
      midthigh tissue composition and muscle volume, and fasting blood samples were
      acquired from 16 same-sex (seven monozygotic, nine dizygotic) middle-aged and
      older twin pairs. The consistently active twins had 20 % higher knee extension
      forces than their inactive co-twins (p = 0.006) although the active twins had
      only 4 % higher midthigh muscle cross-sectional areas (p = 0.072). These results
      were similar in intrapair analysis in which only the seven identical twin pairs
      were included. The ratio between the area of midthigh fat and muscle tissues was
      significantly lower among the active twins (0.65 vs. 0.48, p = 0.006). The active
      twins had also lower fasting plasma glucose levels (5.1 vs 5.6 mmol/l, p =
      0.041). The area of midthigh intramuscular (extramyocellular) fat was associated
      with the markers of glucose homeostasis, especially with glycated hemoglobin, and
      these associations were emphasized by the diabetic and inactive twins. Regular
      exercise throughout the adult life retains muscle strength and quality but not
      necessarily mass. The regular use of muscles also prevents from the accumulation
      of intramuscular fat which might be related to maintained glucose metabolism and,
      thus, prevention of metabolic disorders.

PMID- 23124703
TI  - Netrin-4 overexpression suppresses primary and metastatic colorectal tumor
      progression.
AB  - Tumor angiogenesis is closely associated with clinical staging and has been
      proposed to correlate with clinical response in terms of subsequent metastases
      following primary resection. Netrin-4 (NT-4) regulates angiogenic responses.
      Therefore, we sought to examine the effects of NT-4 on the primary tumor growth
      of colon cancer cells, liver and lung metastases of colon cancer cells, and
      responses following primary tumor resection. We used 3 different mouse models of
      orthotopic primary tumor and liver and lung metastases, comparing 2 human colon
      cancer cells lines: wild-type (low expression of NT-4) and NT-4 (overexpression
      of NT-4) LS174 cells. NT-4 overexpression inhibited the primary tumor growth of
      colorectal LS174 xenografts in nude mice (144.3+/-12.9 vs. 62.4+/-4.5 mm3;
      p<0.0001) as well as its related local and systemic recurrence (38 vs. 0%;
      p<0.01). NT-4 overexpression also markedly decreased colorectal cancer
      progression in terms of tumor number and volume of liver metastases in the NT-4
      group of the orthotopic liver metastasis model (25 vs. 90% and 4+/-1 vs. 709+/
      190 mm3, p<0.001 and p<0.05). Collectively, our findings indicate that NT-4
      overexpression decreases colorectal lung metastasis and its associated lymph node
      involvement. NT-4 overexpression decreases tumor recurrence and metastasis after
      surgical resection, likely via an anti-angiogenic effect. These observations
      suggest that NT-4 may hold therapeutic potential in the treatment of colorectal
      cancer growth and major metastatic sites.

PMID- 23124704
TI  - Finding a role for leptin in the regulation of the Th17 response in experimental
      arthritis: comment on the article by Deng et al.

PMID- 23124705
TI  - Blood oxygenation level-dependent (BOLD) contrast magnetic resonance imaging
      (MRI) for prediction of breast cancer chemotherapy response: a pilot study.
AB  - PURPOSE: To determine whether a simple noninvasive method of assessing tumor
      oxygenation is feasible in the clinical setting and can provide useful,
      potentially predictive information. Tumor microcirculation and oxygenation play
      critical roles in tumor growth and responsiveness to cytotoxic treatment and may
      provide prognostic indicators for cancer therapy. Deoxyhemoglobin is paramagnetic
      and can serve as an endogenous contrast agent causing signal loss in echo planar
      magnetic resonance imaging (MRI) (blood oxygenation level-dependent [BOLD]-MRI).
      We used BOLD-MRI to provide early evaluation of response to neoadjuvant
      chemotherapy in patients with locally advanced breast cancer. MATERIALS AND
      METHODS: MRI was performed on 11 patients with biopsy-proven malignancy. MRI
      exams were scheduled before, during, and after chemotherapy. The BOLD study
      applied a 6-minute oxygen breathing challenge. RESULTS: Seven patients
      successfully completed the exams. Before chemotherapy, BOLD contrast enhancement
      was observed in all tumors, but the patients, who ultimately had complete
      pathological response, exhibited a significantly higher BOLD response to oxygen
      breathing. CONCLUSION: We have successfully implemented an oxygen-breathing
      challenge BOLD contrast technique as part of the standard breast MRI exam in
      patients with locally advanced breast cancer. The preliminary observation that a
      large BOLD response correlated with better treatment response suggests a
      predictive capability for BOLD MRI.

PMID- 23124707
TI  - Diffusely infiltrative squamous cell carcinoma of the esophagus presenting as a
      case with diagnostic difficulty.
AB  - We report a rare case of diffusely infiltrative squamous cell carcinoma of the
      esophagus. The patient, a 68-year-old man, was admitted to our hospital for
      investigation of dysphagia. Esophagography and upper gastrointestinal endoscopy
      revealed esophageal stenosis and gastric cancer. As a biopsy from the esophagus
      revealed no sign of malignancy, he underwent only distal gastrectomy. After 3
      months, the stenosis became worse. Again, biopsy from a gastrointestinal
      endoscopy showed no malignancy, but endobronchial ultrasound-guided
      transbronchial needle aspiration revealed squamous cell carcinoma of the
      esophagus. Despite various treatments, the patient died of disease progression 20
      months after its onset. Autopsy revealed diffusely infiltrative squamous cell
      carcinoma of the esophagus, which is a rare malignancy with few case reports
      documented.

PMID- 23124706
TI  - Therapeutic application of mesenchymal stem cells in bone and joint diseases.
AB  - Mesenchymal stem cells (MSCs), the non-hematopoietic progenitor cells, are multi
      potent stem cells from a variety of tissues with the capability of self-renewal,
      proliferation, differentiation into multi-lineage cell types, as well as anti
      inflammatory and immunomodulatory. These properties make MSCs an ideal source of
      cell therapy in bone and joint diseases. This review describes the advances of
      animal study and preliminary clinical application in the past few years, related
      to MSC-based cell therapy in the common bone and joint diseases, including
      osteoarthritis, rheumatoid arthritis, osteoporosis, osteonecrosis of the femoral
      head and osteogenesis imperfecta. It highlights the promising prospect of MSC in
      clinical application of bone and joint diseases. 

PMID- 23124709
TI  - Extraperitoneal colostomy in laparoscopic abdominoperineal resection using a
      laparoscopic retractor.
AB  - Although extraperitoneal colostomy is often performed to prevent postoperative
      parastomal hernia formation following an open abdominoperineal resection of lower
      rectal cancer, it has not been widely employed laparoscopically because of the
      difficulty associated with the extraperitoneal route. This paper describes a
      laparoscopic extraperitoneal sigmoid colostomy using the Endo RetractTM Maxi
      instrument. This surgical technique is easy, and helps to prevent the development
      of parastomal hernias.

PMID- 23124708
TI  - Risk analysis of pulmonary resection for elderly patients with lung cancer.
AB  - PURPOSE: The indications for pulmonary resection in elderly patients with lung
      cancer concomitant with another disease are unclear. We conducted this
      retrospective study to establish the risk factors of complications and survival
      to improve patient selection. METHODS: The subjects were 295 patients aged >= 75
      years, who underwent pulmonary resection for lung cancer. We assessed comorbidity
      according to the Charlson comorbidity index (CCI) and examined risk factors for
      morbidity and the prognostic factors. RESULTS: Postoperative complications
      developed in 55 patients (morbidity 18.6 %). The median survival time was 59.3
      months and the 5-year survival rate was 69.7 %. Multivariate logistic regression
      analyses selected smoking and thoracotomy as risk factors for complications, and
      a history of cerebrovascular disease, cancer stage, and thoracotomy as risk
      factors for a prolonged hospital stay (PHS). Video-assisted thoracic surgery
      (VATS) decreased the risk of morbidity and PHS, and influenced survival.
      Multivariate analysis with the Cox proportional hazard model identified CCI >= 2,
      morbidity, and PHS as unfavorable survival factors, in addition to age >= 80 and
      cancers that were non-adenocarcinoma or advanced. CONCLUSIONS: Although CCI >= 2
      was associated with poorer survival, it was not necessarily a risk factor of
      postoperative complications or PHS. Performing VATS when possible could reduce
      the incidence of postoperative complications and PHS in elderly patients.

PMID- 23124710
TI  - Single ketamine infusion in bipolar depression resistant to antidepressants: are
      neurotrophins involved?
AB  - OBJECTIVES: We investigated serum brain-derived neurotrophin factor (BDNF), nerve
      growth factor (NGF), neurotrophin-3 (NTF3), neurotrophin-4 (NTF4) and the glial
      derived neurotrophic factor (GDNF), in relation to ketamine efficacy, in bipolar
      depressed patients resistant to treatment with antidepressants. METHODS: Twenty
      five patients (4 male, 21 female), aged 27-67 years, with bipolar depression,
      receiving mood-stabilizing medications, were studied. Antidepressants were
      discontinued for at least 7 days before single intravenous ketamine infusion (0.5
      mg/kg body weight). Response to ketamine was defined as >= 50% reduction on 17
      item Hamilton Depression Rating Scale (HDRS) after 1 week, and remission as HDRS
      score <= 7. Serum BDNF, NGF, NTF3, NTF4 and GDNF levels were estimated by enzyme
      linked immunosorbent assay. RESULTS: There were 13 ketamine responders and 12 non
      responders. The remission was obtained in eight and 12 patients after seven and
      14 days, respectively. At baseline, there were no differences between responders
      and non-responders in any of the neurotrophins. Serum BDNF was significantly
      reduced after 7 days in non-responders. Serum NGF, NT3, NT4 and GDNF did not
      significantly change. CONCLUSIONS: The results confirm an antidepressant effect
      of ketamine infusion as an add-on to mood-stabilizing drugs in bipolar depression
      resistant to antidepressant treatment. They may also suggest a possible
      involvement of BDNF in this effect.

PMID- 23124711
TI  - Comparative proteomics of skeletal muscle mitochondria from myostatin-null mice.
AB  - Myostatin, a secreted protein, is a negative regulator of skeletal muscle growth.
      Down-regulating its expression increases skeletal muscle mass that is accompanied
      by a marked change in the fibre composition from one reliant on mitochondrial
      oxidative metabolism to glycolysis. A comparative proteomic investigation of this
      altered metabolism was carried out on mitochondria from the gastrocnemius muscle
      of myostatin-null mice compared with wild-type. Most of the proteins identified
      showed no significant modulation between the 2 phenotypes, but give interesting
      insight into previous observations. Several proteins were modulated, of which
      only one was identified. This protein, having a sequence similar to that of
      aldehyde reductase, was up-regulated in myostatin-null mitochondria, but its
      importance was not established, although it might play a role in the
      detoxification of harmful products of lipid peroxidation.

PMID- 23124712
TI  - Stimulation of superficial zone protein accumulation by hedgehog and Wnt
      signaling in surface zone bovine articular chondrocytes.
AB  - OBJECTIVE: To determine the roles of the hedgehog and Wnt signaling pathways in
      accumulation of superficial zone protein (SZP) in surface zone articular
      chondrocytes. METHODS: Explant cultures of disks of surface zone cartilage or
      isolated chondrocytes from the surface zone of articular cartilage of bovine
      stifle joints were cultured in serum-free chemically defined medium. Accumulation
      of SZP in the culture medium, in response to hedgehog proteins (sonic hedgehog
      [SHH] and Indian hedgehog [IHH]), Wnt proteins (Wnt-3a, Wnt-5a, and Wnt-11),
      agonists of the Wnt/beta-catenin pathway (glycogen synthase kinase 3beta [GSK
      3beta] inhibitors), and antagonists of the Wnt/beta-catenin pathway, was
      investigated. The interaction between transforming growth factor beta1 (TGFbeta1)
      and hedgehog proteins or antagonists of the Wnt/beta-catenin pathway was also
      investigated. RESULTS: Hedgehog proteins stimulated SZP accumulation. Activation
      of the Wnt/beta-catenin pathway by Wnt-3a and GSK-3beta inhibitors led to
      inhibition of SZP accumulation; however, Wnt-5a and Wnt-11 had no influence on
      SZP accumulation. Conversely, antagonists of the Wnt/beta-catenin pathway
      stimulated SZP accumulation. In addition, there were combinatorial effects of
      TGFbeta1 and hedgehog proteins or antagonists of the Wnt/beta-catenin pathway on
      SZP accumulation. CONCLUSION: SHH and IHH signaling has a stimulatory effect on
      SZP accumulation in surface zone cartilage and isolated articular chondrocytes.
      These findings provide insight into the regulatory mechanisms of articular
      cartilage homeostasis and maintenance by morphogens.

PMID- 23124713
TI  - Perceived discrimination and peer victimization among African American and Latino
      youth.
AB  - Perceptions of racial discrimination constitute significant risks to the
      psychological adjustment of minority youth. The present study examined the
      relationship between perceived racial discrimination and peer nominations of
      victimization among 173 (55 % female) African American, European American and
      Latino youth. All respondents completed peer nominations of victimization status
      whereas the African American and Latino youth completed subjective measures of
      racial discrimination. The results indicated that African American and Latino's
      subjective perceptions of racial discrimination were linked to nominations of
      overt and relational victimization when rated by their European American peers.
      The results suggest that there is consistency between African American and Latino
      youth's perceptions of racial discrimination and nominations of peer
      victimization by their European American peers.

PMID- 23124714
TI  - A quantitative analysis of branching, growth cone turning, and directed growth in
      zebrafish retinotectal axon guidance.
AB  - The topographic projection from the eye to the tectum (amphibians and
      fish)/superior colliculus (birds and mammals) is a paradigm model system for
      studying mechanisms of neural wiring development. It has previously been proposed
      that retinal ganglion cell axons use distinct guidance strategies in fish vs.
      mammals, with direct guidance to the tectal target zone in the former and
      overshoot followed by biased branching toward the target zone in the latter. Here
      we visualized individual retinal ganglion cell axons as they grew over the tectum
      in zebrafish for periods of 10-21 hours and analyzed these results using an array
      of quantitative measures. We found that, although axons were generally guided
      directly toward their targets, this occurred without growth cone turning.
      Instead, axons branched dynamically and profusely throughout pathfinding, and
      successive branches oriented growth cone extension toward a target zone in a
      stepwise manner. These data suggest that the guidance strategies used between
      fish and mammals may be less distinct than previously thought.

PMID- 23124715
TI  - Assessing the relative and absolute reliability of the Falls Efficacy Scale
      International questionnaire in elderly individuals with increased fall risk and
      the questionnaire's convergent validity in elderly women with osteoporosis.
AB  - The Falls Efficacy Scale-International (FES-I) is a highly reliable questionnaire
      for assessing fear of falling in elderly individuals with increased fall risk and
      has low or no convergent validity with balance performance tests and health
      related quality of life (HRQL) among elderly women with osteoporosis, which
      indicates that both measurements should be included as they are measuring
      different components. INTRODUCTION: Fear of falling is increased in elderly
      individuals with osteoporosis and FES-I is a widely used questionnaire to assess
      fear of falling. There is limited evidence of the reliability and convergent
      validity in elderly with increased risk of falling and osteoporosis. METHODS:
      Reliability and validity study of the FES-I. Community-dwelling elderly with
      increased fall risk, 59 subjects, were recruited to the reliability assessment,
      and 81 women with osteoporosis, in the validity assessment. For the reliability
      assessment, two postal surveys were used. For the validity assessment, we used
      baseline data from an on-going study in women with osteoporosis. The FES-I was
      correlated to a single-item question regarding fear of falling, self-reported
      history of falls, balance performance tests and health-related quality of life.
      RESULTS: The FES-I had very good relative reliability (intra-class correlation
      0.88) and internal consistency reliability (Cronbach's alpha 0.94). The value for
      absolute reliability was a standard error of measure 2.9 (10.6 %), smallest real
      difference 7.9 (29 %). There was "little if any" to "low" correlation between the
      FES-I and the single-item question regarding fear of falling and self-reported
      history of falls, HRQL and balance performance tests. CONCLUSION: The FES-I seems
      to be a highly reliable questionnaire for assessing fear of falling in elderly
      with increased fall risk but has low relation to/convergent validity with balance
      performance and HRQL among elderly women with osteoporosis.

PMID- 23124716
TI  - Circulating activin-A is elevated in postmenopausal women with low bone mass: the
      three-month effect of zoledronic acid treatment.
AB  - Activin-A is expressed in bone and seems to regulate osteoclastogenesis. In this
      study, serum activin-A was increased in postmenopausal women with low bone mass
      and was positively correlated to age and negatively to lumbar spinal bone mineral
      density (BMD). Serum activin-A levels did not change 3 months after zoledronic
      acid infusion. INTRODUCTION: The aims of the study were to evaluate prospectively
      the circulating activin-A levels in postmenopausal women with low bone mass and
      explore possible correlations with clinical and laboratory data, as well as the 3
      month effect of zoledronic acid infusion. METHODS: Postmenopausal women with low
      bone mass assigned to receive zoledronic acid infusion (Patients, n = 47) and age
      matched, postmenopausal women with normal bone mass (Controls, n = 27) were
      recruited on an outpatient basis. Main outcome measurement was serum activin-A
      levels. RESULTS: Serum activin-A was higher in patients at baseline compared to
      controls (p < 0.001) and activin-A in the serum of patients and controls was
      positively correlated with age (Spearman's coefficient of correlation [rs] =
      0.325; p = 0.005) and negatively with lumbar spinal (LS) BMD (rs = -0.425; p <
      0.001). In multiple linear regression analysis, only age (B = 8.93; 95 % CI =
      4.39-13.46; p < 0.001) was associated with serum activin-A levels at baseline,
      independent from group (patients or controls), previous anti-osteoporotic
      treatment, LS BMD and follicle-stimulating hormone. Circulating activin-A levels
      were not affected 3 months after zoledronic acid infusion. CONCLUSIONS: Serum
      activin-A is increased in postmenopausal women with low bone mass compared with
      postmenopausal women with normal bone mass and is positively correlated to age
      and negatively to LS BMD.

PMID- 23124718
TI  - Extracardiac juvenile rhabdomyoma of the larynx: a rare pathological finding.
AB  - The extracardiac juvenile rhabdomyoma is extremely rare in the field of
      Otorhinolaryngology. The tumour usually arises from the soft tissue of the face
      or from mucosal sites, especially the oropharynx and the oral cavity but only
      sporadic endolaryngeal cases have been described in literature so far with
      predominance of young males. Here, we describe the very rare case of
      endolaryngeal extracardiac juvenile rhabdomyoma in a 42-year-old male. Clinical
      examination showed a mass of the right vocal cord, resembling a cystic lesion.
      Microlaryngoscopy revealed a non-encapsulated lesion and histopathology including
      immunohistochemistry which consecutively led to the correct diagnosis. This case
      suggests that the endolaryngeal extracardiac juvenile rhabdomyoma can be easily
      confused with a vocal cord cyst. Malignant transformations have not been reported
      but recurrences have been described. When total excision cannot be accomplished,
      reoperation or narrow follow-up is indicated to prevent advanced revision
      surgeries.

PMID- 23124720
TI  - Multicentre European study of preoperative biliary drainage for hilar
      cholangiocarcinoma.
AB  - BACKGROUND: Indications for preoperative biliary drainage (PBD) in the context of
      hepatectomy for hilar malignancies are still debated. The aim of this study was
      to investigate current European practice regarding biliary drainage before
      hepatectomy for Klatskin tumours. METHODS: This was a retrospective analysis of
      all patients who underwent formal or extended right or left hepatectomy for hilar
      cholangiocarcinoma between 1997 and 2008 at 11 European teaching hospitals, and
      for whom details of serum bilirubin levels at admission and at the time of
      surgery were available. PBD was performed at the physicians' discretion. The
      primary outcome was 90-day mortality. Secondary outcomes were morbidity and cause
      of death. The association of PBD and of preoperative serum bilirubin levels with
      postoperative mortality was assessed by logistic regression, in the entire
      population as well as separately in the right- and left-sided hepatectomy groups,
      and was adjusted for confounding factors. RESULTS: A total of 366 patients were
      enrolled; PBD was performed in 180 patients. The overall mortality rate was 10.7
      per cent and was higher after right- than left-sided hepatectomy (14.7 versus 6.6
      per cent; adjusted odds ratio (OR) 3.16, 95 per cent confidence interval 1.50 to
      6.65; P = 0.001). PBD did not affect overall postoperative mortality, but was
      associated with a decreased mortality rate after right hepatectomy (adjusted OR
      0.29, 0.11 to 0.77; P = 0.013) and an increased mortality rate after left
      hepatectomy (adjusted OR 4.06, 1.01 to 16.30; P = 0.035). A preoperative serum
      bilirubin level greater than 50 umol/l was also associated with increased
      mortality, but only after right hepatectomy (adjusted OR 7.02, 1.73 to 28.52; P =
      0.002). CONCLUSION: PBD does not affect overall mortality in jaundiced patients
      with hilar cholangiocarcinoma, but there may be a difference between patients
      undergoing right-sided versus left-sided hepatectomy.

PMID- 23124721
TI  - The cost of prescription drugs: a comparison of two countries.

PMID- 23124719
TI  - Resting state functional connectivity of the hippocampus associated with
      neurocognitive function in left temporal lobe epilepsy.
AB  - The majority of patients with temporal lobe epilepsy (TLE) experience
      disturbances of episodic memory from structural damage or dysfunction of the
      hippocampus. The objective of this study was to use functional Magnetic Resonance
      Imaging (fMRI) to identify regions where resting state connectivity to the left
      hippocampus (LH) is correlated with neuropsychological measures of verbal memory
      retention in TLE patients. Eleven left TLE (LTLE) patients and 15 control
      subjects participated in resting state fMRI scans. All LTLE patients underwent
      neuropsychological testing. Resting state functional connectivity maps to the LH
      were calculated for each patient, and subsequently used in a multiple regression
      analysis with verbal memory retention scores as a covariate. The analysis
      identified brain regions whose connectivity to the LH was linearly related to
      memory retention scores across the group of patients. In LTLE patients, right
      sided (contralateral) clusters in the precuneus and inferior parietal lobule
      (IPL) exhibited increased connectivity to the LH with increased memory retention
      score; left sided (ipsilateral) regions in the precuneus and IPL showed increased
      connectivity to the LH with decreased retention score. Patients with high memory
      retention scores had greater connectivity between the LH-right parietal clusters
      than between the LH-left parietal clusters; in contrast, control subjects had
      significantly and consistently greater LH-left hemisphere than LH-right
      hemisphere connectivity. Our results suggest that increased connectivity in
      contralateral hippocampal functional pathways within the episodic verbal memory
      network represents a strengthening of alternative pathways in LTLE patients with
      strong verbal memory retention abilities.

PMID- 23124722
TI  - Local antimicrobial administration for prophylaxis of surgical site infections.
AB  - Despite a lack of consensus guidelines, local antibiotic administration for
      prophylaxis of surgical site infections is used during many surgical procedures.
      The rationale behind this practice is to provide high antibiotic concentrations
      at the site of surgery while minimizing systemic exposure and adverse effects.
      Local antibiotic administration for surgical site prophylaxis has inherent
      limitations in that antibiotics are applied after the incision is made, rather
      than the current standard for surgical site prophylaxis that recommends providing
      adequate antibiotic concentrations at the site before the incision. The efficacy
      and safety of local application of antibiotics for surgical site prophylaxis have
      been assessed in different types of surgery with a variety of antibiotic agents
      and methods of application. We identified 22 prospective, randomized, controlled
      trials that evaluated local application of antibiotics for surgical site
      prophylaxis. These trials were subsequently divided and analyzed based on the
      type of surgical procedure: dermatologic, orthopedic, abdominal, colorectal, and
      cardiothoracic. Methods of local application analyzed included irrigations,
      powders, ointments, pastes, beads, sponges, and fleeces. Overall, there is a
      significant lack of level I evidence supporting this practice for any of the
      surgical genres evaluated. In addition, the literature spans several decades, and
      changes in surgical procedures, systemic antibiotic prophylaxis, and microbial
      flora make conclusions difficult to determine. Based on available data, the
      efficacy of local antibiotic administration for the prophylaxis of surgical site
      infections remains uncertain, and recommendations supporting this practice for
      surgical site prophylaxis cannot be made.

PMID- 23124723
TI  - Performance of new anticoagulants for thromboprophylaxis in patients undergoing
      hip and knee replacement surgery.
AB  - Venous thromboembolism (VTE) represents one of the most preventable complications
      that occur during hospitalization, and measurement of hospital-associated VTE is
      becoming a key component in hospital quality measures. Guidelines for the
      prevention of deep vein thrombosis and pulmonary embolism have been published by
      several organizations to guide quality of care; however, some of the guidelines
      are divergent in their recommendations. This disagreement among guidelines is
      most pronounced in patients undergoing major orthopedic surgery. The advent of
      newer anticoagulants, which are now approved or in late-phase development, have
      already had an effect on the guidelines and may also affect quality measures in
      the future. In this article, we review the burden of VTE in patients undergoing
      major orthopedic surgery, highlight the differences in the guidelines, and
      examine the new anticoagulants as they are related to VTE prophylaxis in this
      patient group.

PMID- 23124724
TI  - Recurrent peritoneal carcinomatosis in the scrotum in a patient with a history of
      mucocele of the appendix.
AB  - Paratesticular metastases are rare entities and a paratesticular metastasis of a
      mucinous appendiceal adenocarcinoma with peritoneal carcinomatosis has not been
      reported in the literature in the last 15 years. We present a case of mucinous
      appendiceal adenocarcinoma that progressed to peritoneal carcinomatosis. Twenty
      months following surgery and intraperitoneal therapy, the patient presented with
      testicular pain and swelling. Ultrasound examination raised suspicion for a
      neoplastic process and pathology confirmed a metastatic mucinous adenocarcinoma
      of appendiceal origin. Radiologists should be cognizant of potential
      paratesticular metastases in patients with a known history of malignancy with new
      testicular pain and swelling.

PMID- 23124726
TI  - Engineering of complex order and the macroscopic deformation of liquid crystal
      polymer networks.
AB  - Rise or fall: Complex-structured freestanding polymer films with molecular order
      in three dimensions were prepared through photoalignment of polymerizable liquid
      crystals. The resulting films deform into cone and saddle shapes upon heating.

PMID- 23124725
TI  - Effect of atypical antipsychotics on antioxidant enzyme activities in human
      erythrocytes (in vitro study).
AB  - OBJECTIVE: This study was set out to examine the impact of atypical antipsychotic
      drugs: aripiprazole, clozapine, ziprasidone, olanzapine, quetiapine, sertindole
      and amisulpride on the activity of antioxidant defence enzymes in human
      erythrocytes in vitro. METHODS: Cu,Zn-superoxide dismutase (SOD1), catalase
      (CAT), selenium-dependent glutathione peroxidase and glutathione reductase
      activities were determined after drugs incubation with blood of 15 apparently
      healthy non-smoking male volunteers (ages 23-39) for 1 h at 37  degrees C.
      RESULTS: A statistically significant increase in SOD1 activity was found in
      samples incubated with aripiprazole (p < 0.01) and quetiapine (p < 0.05) compared
      with incubated control. SOD1 activity profile following native polyacrylamide gel
      electrophoresis indicates that aripiprazole and quetiapine protect enzyme
      activity from inhibition with hydrogen peroxide. Our results showed that
      sertindole decreases activity of CAT comparing with control non-treated
      erythrocytes. Moreover, in sertindole treated erythrocytes, negative correlation
      between SOD1 and glutathione peroxidase activities was found. Increased amount of
      hydrogen peroxide in such situation may leave erythrocytes and transform their
      role in circulation from anti-oxidative to pro-oxidative. CONCLUSIONS: Our
      results indicate that mechanism through sertindole could express its in vivo
      toxic effects and point toward possible (neuro)protective effects of aripiprazole
      and quetiapine.

PMID- 23124727
TI  - Milwaukee shoulder syndrome affecting the elbow.

PMID- 23124728
TI  - Radon in indoor concentrations and indoor concentrations of metal dust particles
      in museums and other public buildings.
AB  - The aim of this study was to evaluate the public and occupational exposure to
      radon and metal-bearing particles in museums and public buildings located in the
      city of Rio de Janeiro, Brazil. For this study, four buildings were selected: two
      historic buildings, which currently house an art gallery and an art museum; and
      two modern buildings, a chapel and a club. Integrated radon concentration
      measurements were performed using passive radon detectors with solid state
      nuclear track detector-type Lexan used as nuclear track detector. Air samplers
      with a cyclone were used to collect the airborne particle samples that were
      analyzed by the particle-induced X-ray emission technique. The average unattached
      radon concentrations in indoor air in the buildings were above 40 Bq/m(3), with
      the exception of Building D as measured in 2009. The average radon concentrations
      in indoor air in the four buildings in 2009 were below the recommended reference
      level by World Health Organization (100 Bq/m(3)); however, in 2011, the average
      concentrations of radon in Buildings A and C were above this level, though lower
      than 300 Bq/m(3). The average concentrations of unattached radon were lower than
      148 Bq/m(3) (4pCi/L), the USEPA level recommended to take action to reduce the
      concentrations of radon in indoor air. The unattached-radon average
      concentrations were also lower than the value recommended by the European Union
      for new houses. As the unattached-radon concentrations were below the
      international level recommended to take action to reduce the radon concentration
      in air, it was concluded that during the period of sampling, there was low risk
      to human health due to the inhalation of unattached radon in these four
      buildings.

PMID- 23124729
TI  - Leflunomide addition in patients with articular manifestations of psoriatic
      arthritis resistant to methotrexate.
AB  - In contrast to rheumatoid arthritis, in psoriatic arthritis (PsA), the efficacy
      of disease-modifying antirheumatic drugs (DMARDs) combination has not been
      documented. We conducted a retrospective study to evaluate the effectiveness of
      leflunomide (LEF) addition in 11 PsA patients with articular manifestations that
      failed to respond to methotrexate (MTX) monotherapy [disease activity score in 28
      joints (DAS28) > 3.2)]. Eight of them, all with moderate disease activity (DAS28
      < 5.1) at baseline, tolerated the combination. A statistically significant
      improvement of the mean DAS28, based on erythrocyte sedimentation rate (ESR), and
      its variables, and C-reactive protein (CRP) at 12-16 weeks after LEF addition was
      observed. Mean change of DAS28 in patients with polyarticular disease did not
      differ compared with those with oligoarticular. Based on the European League
      Against Rheumatism (EULAR) response criteria, none of our patients achieved a
      good response, seven had a moderate response, and one was a non-responder. The
      two patients with the lower DAS28 at baseline attained low disease activity (LDA,
      DAS28 <= 3.2), while none reached remission (DAS28 <= 2.6). Achievement of
      clinical remission or at least LDA has been recently proposed as the goal of
      treatment in PsA. Our results imply that LEF addition may serve as an alternative
      therapeutic modality for patients with moderately active PsA and, as lower as
      possible, residual disease activity after the initial therapy with MTX alone.

PMID- 23124730
TI  - Exercise capacity in relation to autoantibodies in systemic sclerosis patients.
AB  - Autoantibodies have been detected in systemic sclerosis patients, and typical
      clinical features regarding organ involvement by each autoantibody have been
      reported. To reveal differences in exercise intolerance in patients with either
      anti-topoisomerase-I or anti-centromere antibodies, 53 systemic sclerosis
      patients were investigated retrospectively. A 6-min walking distance showed no
      significant differences (P = 0.090) between autoantibodies, while exercise
      induced hypoxia during the 6-min walking test was significant in subjects with
      the anti-topoisomerase-I antibody (P = 0.033). The percent predicted of vital
      capacity, the diffusion capacity of the lung for carbon monoxide, and the
      modified Rodnan skin score were affected more in subjects with the anti
      topoisomerase-I antibody than the anti-centromere antibody. The main parameter
      affecting the 6-min walking distance was the percent predicted of vital capacity
      for each autoantibody, and there was a significant positive relationship for all
      subjects (R (2) = 0.30, P < 0.0001). Exercise-induced hypoxia was also shown in
      the more affected subjects in the percent predicted of vital capacity and the
      diffusion capacity of the lung for carbon monoxide. Lung parameters were
      suggested to be more important factors determining exercise intolerance and
      induced hypoxia than detected autoantibodies.

PMID- 23124731
TI  - Nontyphoid Salmonella-infected mycotic aneurysm in a patient with rheumatoid
      arthritis.

PMID- 23124732
TI  - Prevalence and severity of insomnia in chronic low back pain patients.
AB  - The purpose of this study was to assess prevalence and severity of insomnia in
      participants diagnosed with chronic low back pain (CLBP) and to identify factors
      associated with this insomnia. One hundred CLBP consenting participants were
      recruited. Sociodemographic, CLBP features and sleep characteristics were
      collected. Patients answered validated measures of insomnia severity and fatigue.
      Statistical analysis examined the relationship between insomnia, sociodemographic
      characteristics of patients and CLBP parameters. Seventy-eight percent of
      patients suffered from insomnia. Insomnia due to back pain was reported in 64 %
      of cases. Insomnia was early, middle and late in, respectively, 39, 60 and 41 %
      of patients. Insomnia was sub-threshold, moderate and severe in, respectively,
      34, 42 and 2 % of patients. ISI Global score was at 18.07 +/- 7.3. ISI correlated
      significantly with pain intensity (r = 0.587; p < 0.0001), fatigue level (r =
      0.495; p < 0.0001) and body mass index (r = -0.209; p = 0.03). Multiple linear
      regression models have revealed that pain intensity (beta = 1.984; 95 % CI (1.517
      2.451); p < 0.0001) and fatigue (beta = 0.284; 95 % CI (0.192-0.377); p < 0.0001)
      were the strongest determinants for predicting insomnia in CLBP patients. Our
      study suggests that the prevalence of insomnia is important in CLBP patients,
      occurring especially at the middle of sleep. Insomnia was essentially sub
      threshold or moderate. Back pain and fatigue experienced by patients were the
      strongest factors associated with this insomnia.

PMID- 23124733
TI  - Kawasaki disease without fever in a Costa Rican girl: first report from Central
      America.

PMID- 23124734
TI  - The co-occurrence of Hashimoto thyroiditis in primary Sjogren's syndrome defines
      a subset of patients with milder clinical phenotype.
AB  - To evaluate in a cohort of 100 consecutive patients affected by primary Sjogren's
      syndrome (pSS) the incidence of Hashimoto thyroiditis (HT) and to compare the
      clinical features and the laboratory parameters of patients affected by pSS with
      and without concomitant HT. In 100 consecutive patients affected by pSS, the
      occurrence of other autoimmune diseases was recorded and a full examination of
      thyroid function obtained. HT was associated with pSS in 27 cases. The comparison
      between pSS cases with and without HT showed that only patients with isolated pSS
      had low C4 level [p = 0.032, OR (IC 95 %) 230 (13.13-4,046)]. In addition, only
      patients affected by pSS without HT had evidence of cryoglobulins, cutaneous
      vasculitis with palpable purpura, peripheral neuropathy, and development of
      lymphoma, although all these manifestations were observed in a 4.1-8.2 % of the
      cases, without reaching statistical significance. The association of HT in
      patients suffering from pSS defines a subset of patients with milder disease and
      normal C4 levels.

PMID- 23124735
TI  - Implementing combination DMARDs strategy in early RA not as nice as we like?

PMID- 23124736
TI  - Emerging role of Fluorine-18-fluorodeoxyglucose positron emission tomography in
      patients with retroperitoneal fibrosis: a systematic review.
AB  - To systematically review the literature data on the role of Fluorine-18
      fluorodeoxyglucose positron emission tomography and positron emission
      tomography/computed tomography (FDG-PET and PET/CT) in patients with
      retroperitoneal fibrosis (RF), PubMed/MEDLINE, Embase and Scopus databases were
      searched for articles that evaluated the usefulness of FDG-PET and PET/CT in
      patients with RF from inception to March 31, 2012. Review articles or editorials,
      articles not in the field of interest of this review, case reports and
      preclinical studies were excluded. Only studies including FDG-PET or PET/CT scans
      performed in at least three patients with RF were included. Ten studies
      comprising a total of 101 patients with RF were found. The main findings of the
      included studies are described. FDG-PET and PET/CT are feasible and suitable
      imaging methods for evaluating patients with RF. These functional imaging
      techniques seem to be useful both in the diagnosis (mainly in the assessment of
      activity and extent of the disease) and in evaluating the treatment response in
      patients with RF. Given the heterogeneity among the various studies for PET
      analysis and diagnostic criteria, a standardization of the technique is required
      in order to achieve reproducible and inter-observer independent results.
      Moreover, further studies are needed to substantiate the role of FDG-PET and
      PET/CT in patients with RF.

PMID- 23124737
TI  - IRAK1, a potential therapeutic target for rheumatoid arthritis?

PMID- 23124738
TI  - The role of type III secretion system 2 in Vibrio parahaemolyticus pathogenicity.
AB  - Vibrio parahaemolyticus, a Gram-negative marine bacterial pathogen, is emerging
      as a major cause of food-borne illnesses worldwide due to the consumption of raw
      seafood leading to diseases including gastroenteritis, wound infection, and
      septicemia. The bacteria utilize toxins and type III secretion system (T3SS) to
      trigger virulence. T3SS is a multi-subunit needle-like apparatus used to deliver
      bacterial proteins, termed effectors, into the host cytoplasm which then target
      various eukaryotic signaling pathways. V. parahaemolyticus carries two T3SSs in
      each of its two chromosomes, named T3SS1 and T3SS2, both of which play crucial
      yet distinct roles during infection: T3SS1 causes cytotoxicity whereas T3SS2 is
      mainly associated with enterotoxicity. Each T3SS secretes a unique set of
      effectors that contribute to virulence by acting on different host targets and
      serving different functions. Emerging studies on T3SS2 of V. parahaemolyticus,
      reveal its regulation, translocation, discovery, characterization of its
      effectors, and development of animal models to understand the enterotoxicity.
      This review on recent findings for T3SS2 of V. parahaemolyticus highlights a
      novel mechanism of invasion that appears to be conserved by other marine
      bacteria.

PMID- 23124739
TI  - Reliability of non-culturable virus monitoring by PCR-based detection methods in
      environmental waters containing various concentrations of target RNA.
AB  - Owing to the lack of practical cell culture system for human noroviruses (HuNoV),
      various detection methods based on conventional reverse transcription-PCR (RT
      PCR) and the quantitative real-time PCR have been major tools for monitoring
      environmental water safety. In this study, we showed that the proportion of water
      sample concentrates used for one-step RT-PCR significantly influences false
      negative findings of the non-culturable viruses. In total, 59 archived samples of
      previously analyzed water concentrates were reexamined for HuNoV RNA by the one
      step RT-PCR and semi-nested PCR. Using new aliquots for RNA extraction for every
      trial, up to 20 PCR trials were performed for each archive to determine whether
      the crosscheck results supported the previous determinations. We reconfirmed that
      27.6% (8/29) of the samples were HuNoV-positive samples: 6.7% (1/15) from
      groundwater, 33.3% (3/9) from river water, and 80% (4/5) from treated sewage
      effluent (TSE). These results corresponded to the ratio of previously negative
      HuNoV samples now identified as positive (8/30): 6.7% (1/15) from groundwater,
      20% (1/5) from river water, and 60% (6/10) from TSE. To elucidate the cause of
      these results, 16 different concentrations of murine norovirus (MNV) RNA (from
      2*10(2) to 8*10(3) copies, divided into 10 tubes for each concentration) were
      subjected to one-step RT-PCR. The detection frequency and reproducibility
      decreased sharply when the number of MNV RNA copies fell below threshold levels.
      These observations suggest that the proportion of water concentrate used for PCR
      based detection should be considered carefully when deciding viral presence in
      certain types of environmental water, particularly in regard with legal controls.

PMID- 23124740
TI  - Pyrosequencing analysis of the bacterial communities in the guts of honey bees
      Apis cerana and Apis mellifera in Korea.
AB  - The bacterial communities in the guts of the adults and larvae of the Asian honey
      bee Apis cerana and the European honey bee Apis mellifera were surveyed by
      pyrosequencing the 16S rRNA genes. Most of the gut bacterial 16S rRNA gene
      sequences were highly similar to the known honey bee-specific ones and affiliated
      with Pasteurellaceae or lactic acid bacteria (LAB). The numbers of operational
      taxonomic units (OTUs, defined at 97% similarity) were lower in the larval guts
      (6 or 9) than in the adult guts (18 or 20), and the frequencies of
      Pasteurellaceae-related OTUs were higher in the larval guts while those of LAB
      related OTUs in the adult guts. The frequencies of Lactococcus, Bartonella,
      Spiroplasma, Enterobacteriaceae, and Flavobacteriaceae-related OTUs were much
      higher in A. cerana guts while Bifidobacterium and Lachnospiraceae-related OTUs
      were more abundant in A. mellfera guts. The bacterial community structures in the
      midguts and hindguts of the adult honey bees were not different for A. cerana,
      but significantly different for A. mellifera. The above results substantiated the
      previous observation that honey bee guts are dominated by several specific
      bacterial groups, and also showed that the relative abundances of OTUs could be
      markedly changed depending on the developmental stage, the location within the
      gut, and the honey bee species. The possibility of using the gut bacterial
      community as an indicator of honey bee health was discussed.

PMID- 23124741
TI  - Comparative study of olive oil mill wastewater treatment using free and
      immobilized Coriolopsis polyzona and Pycnoporus coccineus.
AB  - The efficiency of the two white-rot fungi Pycnoporus coccineus and Coriolopsis
      polyzona in the Olive Oil Mill Wastewater (OOMW) treatment was investigated. Both
      fungi were active in the decolourisation and COD removal of OOMW at 50 g/L COD,
      but only the first fungus remains effective on the crude effluent (COD=100 g/L).
      Moreover P. coccineus was less affected by oxygen supplementation and exhibited a
      high tolerance to agitation in comparison to C. polyzona. However, it required a
      nitrogen supplementation to obtain faster and higher COD removal. To overcome the
      negative effect of agitation on fungi growth and efficiency, immobilisation of C.
      polyzona and P. coccineus in polyurethane foam was applied. The immobilized
      system showed better COD decreases during three consecutive batches without
      remarkable loss of performances. The results obtained in this study suggested
      that immobilized C. polyzona and especially immobilized P. coccineus might be
      applicable to a large scale for the removal colour and COD of OOMW.

PMID- 23124744
TI  - Functional characterization of the genes tauO, tauK, and tauI in the biosynthesis
      of tautomycetin.
AB  - Tautomycetin is a specific protein phosphatase I inhibitor. In an effort to
      elucidate the biosynthetic mechanism of tautomycetin, we inactivated genes of the
      tautomycetin biosynthetic gene cluster, tauI, tauO, and tauK, which encode for
      putative P450 oxidase, citryl-CoA lyase, and esterase enzymes, respectively. The
      mutant STQ0606 (DeltatauO) did not produce any detectable amount of tautomycetin
      intermediates but could convert dialkylmaleic anhydride to tautomycetin, strongly
      indicating that TauO was involved in dialkylmaleic anhydride biosynthesis.
      STQ1211 (DeltatauK) accumulated dialkylmaleic anhydride, whereas the
      cofermentation of STQ1211 (DeltatauK) and STQ0606 (DeltatauO) restored the
      production of tautomycetin. Together, these results suggest that TauK was
      responsible for the conjugation of dialkylmaleic anhydride and the polyketide
      moiety in tautomycetin biosynthesis. The disruption of tauI resulted in the
      accumulation of 5-des-keto-tautomycetin, revealing that TauI was responsible for
      the oxidation at C5 as the last step. Although the shunt pathways were involved
      in the biosynthesis of tautomycetin, the main post-polyketide synthase tailoring
      steps were dehydration, decarboxylation and oxidation, taking place
      consecutively. This study allowed us to predict the biosynthesis of tautomycetin
      more accurately and provided novel insights into the mechanism of the
      biosynthesis of tautomycetin.

PMID- 23124743
TI  - PyroTrimmer: a software with GUI for pre-processing 454 amplicon sequences.
AB  - The ultimate goal of metagenome research projects is to understand the ecological
      roles and physiological functions of the microbial communities in a given natural
      environment. The 454 pyrosequencing platform produces the longest reads among the
      most widely used next generation sequencing platforms. Since the relatively
      longer reads of the 454 platform provide more information for identification of
      microbial sequences, this platform is dedicated to microbial community and
      population studies. In order to accurately perform the downstream analysis of the
      454 multiplex datasets, it is necessary to remove artificially designed sequences
      located at either ends of individual reads and to correct low-quality sequences.
      We have developed a program called PyroTrimmer that removes the barcodes,
      linkers, and primers, trims sequence regions with low quality scores, and filters
      out low-quality sequence reads. Although these functions have previously been
      implemented in other programs as well, PyroTrimmer has novelty in terms of the
      following features: i) more sensitive primer detection using Levenstein distance
      and global pairwise alignment, ii) the first stand-alone software with a graphic
      user interface, and iii) various options for trimming and filtering out the low
      quality sequence reads. PyroTrimmer, written in JAVA, is compatible with multiple
      operating systems and can be downloaded free at http://pyrotrimmer.kobic.re.kr.

PMID- 23124742
TI  - Characterization of the bacterial and archaeal communities in rice field soils
      subjected to long-term fertilization practices.
AB  - The bacterial and archaeal communities in rice field soils subjected to different
      fertilization regimes for 57 years were investigated in two different seasons, a
      non-planted, drained season (April) and a rice-growing, flooded season (August),
      by performing soil dehydrogenase assay, real-time PCR assay and pyrosequencing
      analysis. All fertilization regimes increased the soil dehydrogenase activity
      while the abundances of bacteria and archaea increased in the plots receiving
      inorganic fertilizers plus compost and not in those receiving inorganic
      fertilizers only. Rice-growing and flooding decreased the soil dehydrogenase
      activity while they increased the bacterial diversity in rice field soils. The
      bacterial communities were dominated by Chloroflexi, Proteobacteria, and
      Actinobacteria and the archaeal communities by Crenarchaeota at the phylum level.
      In principal coordinates analysis based on the weighted Fast UniFrac metric, the
      bacterial and archaeal communities were separated primarily by season, and
      generally distributed along with soil pH, the variation of which had been caused
      by long-term fertilization. Variations in the relative abundance according to the
      season or soil pH were observed for many bacterial and archaeal groups. In
      conclusion, the microbial activity, prokaryotic abundance and diversity, and
      prokaryotic community structure in the rice field soils were changed by season
      and long-term fertilization.

PMID- 23124745
TI  - Identification and characterization of an autolysin gene, atlA, from
      Streptococcus criceti.
AB  - AtlA of Streptococcus mutans is a major autolysin and belongs to glycoside
      hydrolase family 25 with cellosyl of Streptomyces coelicolor. The autolysin gene
      (atlA) encoding AtlA was identified from S. criceti. AtlA of S. criceti comprises
      the signal sequence in the N-terminus, the putative cell-wall-binding domain in
      the middle, and the catalytic domain in the C-terminus. Homology modeling
      analysis of the catalytic domain of AtlA showed the resemblance of the spatial
      arrangement of five amino acids around the predicted catalytic cavity to that of
      cellosyl. Recombinant AtlA and its four point mutants, D655A, D747A, W831A, and
      D849A, were evaluated on zymogram of S. criceti cells. Lytic activity was
      destroyed in the mutants D655A and D747A and diminished in the mutants W831A and
      D849A. These results suggest that Asp655 and Asp747 residues are critical for
      lytic activity and Trp831 and Asp849 residues are also associated with enzymatic
      activity.

PMID- 23124746
TI  - Genome-wide enrichment screening reveals multiple targets and resistance genes
      for triclosan in Escherichia coli.
AB  - Triclosan is a widely used biocide effective against different microorganisms. At
      bactericidal concentrations, triclosan appears to affect multiple targets, while
      at bacteriostatic concentrations, triclosan targets FabI. The site-specific
      antibiotic-like mode-of-action and a widespread use of triclosan in household
      products claimed to possibly induce cross-resistance to other antibiotics. Thus,
      we set out to define more systematically the genes conferring resistance to
      triclosan; A genomic library of Escherichia coli strain W3110 was constructed and
      enriched in a selective medium containing a lethal concentration of triclosan.
      The genes enabling growth in the presence of triclosan were identified by using a
      DNA microarray and confirmed consequently by ASKA clones overexpressing the
      selected 62 candidate genes. Among these, forty-seven genes were further
      confirmed to enhance the resistance to triclosan; these genes, including the FabI
      target, were involved in inner or outer membrane synthesis, cell-surface material
      synthesis, transcriptional activation, sugar phosphotransferase (PTS) systems,
      various transporter systems, cell division, and ATPase and
      reductase/dehydrogenase reactions. In particular, overexpression of pgsA, rcsA,
      or gapC conferred to E. coli cells a similar level of triclosan resistance
      induced by fabI overexpression. These results indicate that triclosan may have
      multiple targets other than well-known FabI and that there are several undefined
      novel mechanisms for the resistance development to triclosan, thus probably
      inducing cross antibiotic resistance.

PMID- 23124747
TI  - Characterization of thermostable deblocking aminopeptidases of archaeon
      Thermococcus onnurineus NA1 by proteomic and biochemical approaches.
AB  - Thermococcus onnurineus NA1 is a hyperthermophilic archaeon that grows optimally
      at >80 degrees C. The deblocking aminopeptidase (DAP) (TNA1-DAP1) encoded in
      Ton_1032 of T. onnurineus NA1 is considered a major DAP. However, four genes
      encoding putative DAP have been identified from a genomic analysis of T.
      onnurineus NA1. A proteomic analysis revealed that all four DAPs were
      differentially induced in YPS culture medium and, particularly, two DAPs (TNA1
      DAP1 and TNA1-DAP2) were dominantly expressed in T. onnurineus NA1. The
      biochemical properties and enzyme activity of DAPs induced in an E. coli
      expression system suggested that the two major DAPs play complementary roles in
      T. onnurineus NA1.

PMID- 23124748
TI  - Selection of a Streptomyces strain able to produce cell wall degrading enzymes
      and active against Sclerotinia sclerotiorum.
AB  - Control of plant pathogen Sclerotinia sclerotiorum is an ongoing challenge
      because of its wide host range and the persistence of its sclerotia in soil.
      Fungicides are the most commonly used method to control this fungus but these can
      have ecotoxicity impacts. Chitinolytic Streptomyces strains isolated from
      Brazilian tropical soils were capable of inhibiting S. sclerotiorum growth in
      vitro, offering new possibilities for integrated pest management and biocontrol,
      with a new approach to dealing with an old problem. Strain Streptomyces sp. 80
      was capable of irreversibly inhibiting fungal growth. Compared to other strains,
      its crude enzymes had the highest chitinolytic levels when measured at 25 degrees
      C and strongly inhibited sclerotia from S. sclerotiorum. It produced four
      hydrolytic enzymes involved in fungal cell wall degradation when cultured in
      presence of the fungal mycelium. The best production, obtained after three days,
      was 0.75 U/ml for exochitinase, 0.9 U/ml for endochitinase, 0.16 U/ml for
      glucanase, and 1.78 U/ml for peptidase. Zymogram analysis confirmed two
      hydrolytic bands of chitinolytic activity with apparent molecular masses of 45.8
      and 206.8 kDa. One glucanase activity with an apparent molecular mass of 55 kDa
      was also recorded, as well as seven bands of peptidase activity with apparent
      molecular masses ranging from 15.5 to 108.4 kDa. Differential interference
      contrast microscopy also showed alterations of hyphal morphology after co
      culture. Streptomyces sp. 80 seems to be promising as a biocontrol agent against
      S. sclerotiorum, contributing to the development of new methods for controlling
      plant diseases and reducing the negative impact of using fungicides.

PMID- 23124749
TI  - In vitro development and transfer of resistance to chlortetracycline in Bacillus
      subtilis.
AB  - The present criteria and rules controlling the approval of the use of probiotics
      are limited to antibiotic resistance patterns and the presence of antibiotic
      resistance genes in bacteria. There is little information available in the
      literature regarding the risk of the usage of probiotics in the presence of
      antibiotic pressure. In this study we investigated the development and transfer
      of antibiotic resistance in Bacillus subtilis selected in vitro by
      chlortetracycline in a stepwise manner. Bacillus subtilis was exposed to
      increasing concentrations of chlortetracyclineto induce in vitro resistance to
      chlortetracycline, and the minimal inhibitory concentrations were determinedfor
      the mutants. Resistant B. subtilis were conjugated with Escherichia coli NK5449
      and Enterococcus faecalis JH2-2 using the filter mating. Three B. subtilis
      tetracycline resistant mutants (namely, BS-1, BS-2, and BS-3) were derived in
      vitro. A tetracycline resistant gene, tet (K), was found in the plasmids of BS-1
      and BS-2. Three conjugates (BS-1N, BS-2N, and BS-3N) were obtained when the
      resistant B. subtilis was conjugated with E. coli NK5449. The conjugation
      frequencies for the BS-1N, BS-2N, and BS-3N conjugates were 4.57*10(-7), 1.4*10(
      7), and 1.3*10(-8), respectively. The tet(K) gene was found only in the plasmids
      of BS-1N. These results indicate that long-term use of probiotics under
      antibiotic selection pressure could cause antibiotic resistance, and the
      resistance gene could be transferred to other bacteria. The risk arising from the
      use of probiotics under antibiotic pressure should be considered in the criteria
      and rules for the safety assessment of probiotics.

PMID- 23124751
TI  - Establishment and characterization of the epithelioma papulosum cyprini (EPC)
      cell line persistently infected with infectious pancreatic necrosis virus (IPNV),
      an aquabirnavirus.
AB  - Infectious pancreatic necrosis virus (IPNV), a type species of aquabirnaviruses
      in the family Birnaviridae, is an etiological agent of infectious pancreatic
      necrosis and has been isolated from epizootics of cultured salmonids. In the
      present study, an epithelioma papulosum cyprini (EPC) cell line persistently
      infected with IPNV (PI-EPC) was experimentally established by subculturing EPC
      cells surviving IPNV infection, and was characterized. PI-EPC cells were
      morphologically indistinguishable from EPC, but continued to grow and yield IPNV.
      PI-EPC cells showed no cytopathic effect due to IPNV inoculation, and
      susceptibility of PI-EPC cells against heterologous viruses was not different
      from that of EPC cells. Only one cell of 10(3.5) PI-EPC cells produced IPNV at
      approximately 10(0.5) 50% tissue culture infectious dose (TCID50)/cell/day, which
      was approximately 1,000 times lower than that of normal EPC cells. PI-EPC cells
      that did not yield IPNV (N-PI-EPC) were screened. The IPNV genome was detected
      from both PI-EPC and N-PI-EPC cells, and the IPNV VP2 structural protein was
      detected from both cell lines, but no other IPNV proteins were observed by
      Western blot analysis with anti-IPNV serum. Thus, multiplication of IPNV in PI
      EPC cells was regulated by some host cell factors, except interferon.

PMID- 23124750
TI  - The production and immunogenicity of human papillomavirus type 58 virus-like
      particles produced in Saccharomyces cerevisiae.
AB  - Human papillomavirus (HPV) is the cause of most cases of cervical cancer. HPV
      type 58 (HPV58) is the second most frequent cause of cervical cancer and high
      grade squamous intraepithelial lesions (HSIL) in Asia and South / Central
      America, respectively. However, there is no vaccine against HPV58, although there
      are commercially available vaccines against HPV16 and 18. In this study, we
      produced HPV58 L1 protein from Saccharomyces cerevisiae, and investigated its
      immunogenicity. We first determined the optimum period of culture for obtaining
      HPV58 L1. We found that a considerable portion of the HPV58 L1 resulting from 48
      h culture cannot be recovered by purification, while the HPV58 L1 resulting from
      144 h culture is recovered efficiently: the yield of HPV58 L1 finally recovered
      from 144 h culture was 2.3 times higher than that from 48 h culture, although the
      production level of L1 protein from 144 h culture was lower than that from 48 h
      culture. These results indicate that the proportion of functional L1 protein from
      144 h-cultured cells is significantly higher than that of 48 h-cultured cells.
      The HPV58 L1 purified from the 144 h culture was correctly assembled into
      structures similar to naturally occurring HPV virions. Immunization with the
      HPV58 L1 efficiently elicited anti-HPV58 neutralizing antibodies and antigen
      specific CD4+ and CD8+ T cell proliferations, without the need for adjuvant. Our
      findings provide a convenient method for obtaining substantial amounts of highly
      immunogenic HPV58 L1 from S. cerevisiae.

PMID- 23124752
TI  - Possible translocation of periodontal pathogens into the lymph nodes draining the
      oral cavity.
AB  - Numerous publications have reported the presence of periodontopathogenic bacteria
      in peripheral and central vascular lesions. However, it is unclear how this
      bacterial translocation occurs. The objective of this study was to investigate
      whether periodontopathic bacteria are translocated to lymph nodes proximal to the
      oral cavity. Obtaining lymph node samples is not ethically feasible unless they
      are excised as part of the surgical management of patients with cancer. This
      study analyzed formalin-fixed and paraffin-embedded lymph nodes, histologically
      negative for cancer cell invasion, that were excised from 66 patients with
      histories of head and neck cancer. Real-time PCR was performed to amplify the 16S
      ribosomal DNA fragments from Porphyromonas gingivalis, Treponema denticola,
      Aggregatibacter actinomycetemcomitans, Tannerella forsythia, and Prevotella
      intermedia. The relationship between bacterial detection and cancer severity,
      gender, and the use of anti-cancer therapy was examined by Fisher's exact test.
      P. gingivalis, T. forsythia, and P. intermedia were present in 17%, 8%, and 8% of
      the samples of submandibular and submental lymph nodes, respectively. There were
      no significant relationships between bacterial detection and the cancer disease
      status, patient gender or use of anticancer therapy. According to these data, it
      appears that the translocation of periodontopathic bacteria may occur via
      lymphatic drainage, irrespective of the cancer disease status, gender or
      anticancer therapy.

PMID- 23124753
TI  - Intestinal intraepithelial TCRgammadelta+ T cells are activated by normal
      commensal bacteria.
AB  - TCRgammadelta(+) T cells play a critical role in protecting the intestinal mucosa
      against pathogenic infection. In the absence of infection, TCRgammadelta(+) T
      cell activation must be continuously regulated by T regulatory cells (Treg) to
      prevent the development of colitis. However, the activation of intestinal
      TCRgammadelta(+) T cells under normal conditions has not been clearly resolved.
      In order to determine TCRgammadelta(+) T cell activation in vivo, we designed an
      NF-kappaB based reporter system. Using the recombinant lentiviral method, we
      delivered the NF-kappaB reporter to isolated TCRgammadelta(+) T cells, which were
      then adoptively transferred into normal mice. Our data indicate that the NF
      kappaB activation level in TCRgammadelta(+) T cells is higher in the intestinal
      intraepithelial layer than in the lamina propria region. In addition, the surface
      expression level of lymphocyte activation marker CD69 in TCRgammadelta(+) T cells
      is also higher in the intestinal intraepithelial layer and this activation was
      reduced by Sulfatrim treatment which removes of commensal bacteria. Collectively,
      our data indicate that the TCRgammadelta(+) T cell population attached to the
      intestinal lumen is constitutively activated even by normal commensal bacteria.

PMID- 23124754
TI  - Antifungal activity of Leuconostoc citreum and Weissella confusa in rice cakes.
AB  - The antifungal activity of organic acids greatly improves the shelf life of bread
      and bakery products. However, little is known about the effect of lactic acid
      fermentation on fungal contamination in rice cakes. Here, we show that lactic
      acid fermentation in rice dough can greatly retard the growth of three fungal
      species when present in rice cakes, namely Cladosporium sp. YS1, Neurospora sp.
      YS3, and Penicillium crustosum YS2. The antifungal activity of the lactic acid
      bacteria against these fungi was much better than that of 0.3% calcium
      propionate. We found that organic acids including lactic and acetic acid, which
      are byproducts of lactic fermentation or can be artificially added, were the main
      antifungal substances. We also found that some Leuconostoc citreum and Weissella
      confusa strains could be good starter species for rice dough fermentation. These
      results imply that these lactic acid bacteria can be applicable to improve the
      preservation of rice cakes.

PMID- 23124755
TI  - Antifungal activity of extracellular hydrolases produced by autolysing
      Aspergillus nidulans cultures.
AB  - Carbon-starving Aspergillus nidulans cultures produce high activities of
      versatile hydrolytic enzymes and, among these, ChiB endochitinase and EngA beta
      1,3-endoglucanase showed significant antifungal activity against various fungal
      species. Double deletion of engA and chiB diminished the antifungal activity of
      the fermentation broths and increased conidiogenesis and long-term viability of
      A. nidulans, but decreased the growth rate on culture media containing weak
      carbon sources. Production of ChiB and EngA can influence fungal communities
      either directly due to their antifungal properties or indirectly through their
      effects on vegetative growth. Our data suggest saprophytic fungi as promising
      future candidates to develop novel biocontrol technologies.

PMID- 23124757
TI  - Next-generation sequencing-based genome-wide mutation analysis of L-lysine
      producing Corynebacterium glutamicum ATCC 21300 strain.
AB  - In order to identify single nucleotide polymorphism and insertion/deletion
      mutations, we performed whole-genome re-sequencing of the enhanced L-lysine
      producing Corynebacterium glutamicum ATCC 21300 strain. In total, 142 single
      nucleotide polymorphisms and 477 insertion/deletion mutations were identified in
      the ATCC 21300 strain when compared to 3,434 predicted genes of the wild-type C.
      glutamicum ATCC 13032 strain. Among them, 110 transitions and 29 transversions of
      single nucleotide polymorphisms were found from genes of the ATCC 21300 strain.
      In addition, 11 genes, involved in the L-lysine biosynthetic pathway and central
      carbohydrate metabolism, contained mutations including single nucleotide
      polymorphisms and insertions/deletions. Interestingly, RT-PCR analysis of these
      11 genes indicated that they were normally expressed in the ATCC 21300 strain.
      This information of genome-wide gene-associated variations will be useful for
      genome breeding of C. glutamicum in order to develop an industrial amino acid
      producing strain with minimal mutation.

PMID- 23124756
TI  - Burkholderia denitrificans sp. nov., isolated from the soil of Dokdo Island,
      Korea.
AB  - A novel, Gram-negative, bacterial strain KIS30-44(T) was identified from wet
      forest soil collected on the Korean island of Dokdo. Growth of the strain was
      observed at 15-30 degrees C, pH 5-9, 0-3% NaCl, and 950 mM KNO(3). KIS30-44(T)
      reduced nitrate to nitrogen gas. Analysis of the 16S rRNA gene sequence showed
      that KIS30-44(T) was phylogenetically related to Burkholderia sacchari,
      Burkholderia mimosarum, and Burkholderia oxyphila (98.1%, 98.0%, and 98.0%
      sequence similarity, respectively). The genomic G+C content was 63.5 mol%. KIS30
      44(T) exhibited less than 52% DNA-DNA relatedness with the type strains of 9
      closely related Burkholderia species. The major isoprenoid quinone was Q-8. The
      polar lipid profile consisted of diphosphatidylglycerol,
      phosphatidylethanolamine, phosphatidylglycerol and two unknown aminolipids. The
      major fatty acids in KIS30-44(T) were C(16:0), C(18:1) omega7c and summed feature
      3 (iso-C(15:0) 2-OH and C(16:1) omega7c), and the strain contained half the
      amount of C(17:0) cyclo found in the 9 closely related Burkholderia species. The
      results of these phenotypic, 16S rRNA gene sequence, DNA-DNA hybridization, and
      chemotaxonomic data indicate that KIS30-44(T) represents a novel species within
      the genus Burkholderia, for which the name Burkholderia denitrificans (Type
      strain KIS30-44(T) =KACC 12733(T) =DSM 24336(T)) is proposed.

PMID- 23124758
TI  - Caenimonas terrae sp. nov., isolated from a soil sample in Korea, and emended
      description of the genus Caenimonas Ryu et al. 2008.
AB  - A white-coloured bacterium, SGM1-15(T), was isolated from a paddy soil sample
      from Suwon, Republic of Korea. The cells were strictly aerobic, Gram-negative and
      curved rod-shaped. A phylogenetic analysis based on 16S rRNA gene sequences
      revealed that strain SGM1-15(T) was closely related to Curvibacter delicatus LMG
      4328(T) (97.6% similarity) and Caenimonas koreensis EMB320(T) (97.5% similarity).
      The major respiratory quinone system was Q-8 and the predominant cellular fatty
      acids were C(16:0) (39.9%), summed feature 3 (C(16:1) omega7c and/or iso-C(15:0)
      2-OH; 24.3%) and C(17:0) cyclo (22.7%). The major polar lipids were
      diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. The
      major polyamines were 2-hydroxypurescine, purescine and spermidine. The DNA G+C
      content was 68.7 mol%. On the basis of the phylogenetic, physiologicl and
      chemotaxonomic data, stain SGM1-15(T) represents a novel species of the genus
      Caenimonas, for which the name Caenimonas terrae sp. nov. is proposed. The type
      strain of Caenimonas terrae is SGM1-15(T) (=KACC 13365(T) =NBRC 106341(T)).

PMID- 23124759
TI  - Envelope diversity, characteristics of V3 region and predicted co-receptor usage
      of human immunodeficiency viruses infecting north Indians.
AB  - Subtypes of human immunodeficiency virus type 1 circulating in 21 north Indian
      patients were characterized based on the partial sequence of the gp120 envelope
      protein. A majority of viruses (85.7%, 18/21) were subtype C, while 14.3% (3/21)
      were subtype A. Sequence analysis revealed that the V3 region was highly
      conserved compared with V4 and V5. The predicted use of co-receptors indicated
      exclusive usage of R5, except for two subtype A viruses (AIIMS279 and AIIMS281).
      Our results demonstrate conservation within the V3 loop of subtype C viruses, and
      suggest the emergence of non-clade C viruses in the north Indian population.

PMID- 23124760
TI  - Construction and characterisation of an antifungal recombinant Bacillus
      thuringiensis with an expanded host spectrum.
AB  - A novel antifungal Bacillus thuringiensis strain 19-22, ssp. kurstaki (H3a3b3c),
      was characterised. This strain included cry1Aa, cry1Ab, cry1Ac, and cry1D, which
      have high insecticidal activities against lepidopteran larvae other than
      Spodoptera exigua. To expand the host spectrum, a cry1E gene whose product is
      active against S. exigua was introduced into the isolate. The transformant
      successfully expressed the Cry1E protein without any loss of its original
      antifungal activities. These results indicate that this recombinant strain
      exhibits dual activities and may be used as an integrated control agent to
      control plant diseases and insect pests.

PMID- 23124761
TI  - Identification of chaperones in freeze tolerance in Saccharomyces cerevisiae.
AB  - Exposure to low temperatures reduces protein folding rates and induces the cold
      denaturation of proteins. Considering the roles played by chaperones in
      facilitating protein folding and preventing protein aggregation, chaperones must
      exist that confer tolerance to cold stress. Here, yeast strains lacking
      individual chaperones were screened for reduced freezing tolerance. In total, 19
      of 82 chaperone-deleted strains tested were more sensitive to freeze-thaw
      treatment than wild-type cells. The reintroduction of the respective chaperone
      genes into the deletion mutants recovered the freeze tolerance. The freeze
      sensitivity of the chaperone-knockout strains was also retained in the presence
      of 20% glycerol.

PMID- 23124762
TI  - Winogradskyella jejuensis sp. nov., a marine bacterium isolated from a brown alga
      Carpopeltis affinis.
AB  - A Gram-negative, orange-pigmented, rod-shaped bacterium, designated strain
      CP32(T) was isolated from a brown alga Carpopeltis affinis collected on the coast
      of Jeju Island, Republic of Korea. The isolate grew at 10-37 degrees C (optimum
      25 degrees C) and at pH 6.5-9.5 (optimum pH 7.0). The 16S rRNA gene sequence of
      the isolate showed much similarity with the type strains of recognized species of
      the genus Winogradskyella (94.0-96.6%). The most closely related species were
      Winogradskyella echinorum KMM 6211(T), Winogradskyella ulvae KMM 6390(T),
      Winogradskyella thalassocola KMM 3907(T), Winogradskyella poriferorum UST030701
      295(T), and Winogradskyella eximia KMM 3944(T). The major respiratory quinone was
      menaquinone-6 (MK-6) and the predominant cellular fatty acids were iso-C(15:1) G
      (24.8%), iso-C(15:0) (23.4%), and iso-C(17:0) 3-OH (11.6 %). The DNA G+C content
      was 33.3 mol%. The polar lipid profile was composed of phosphatidylethanolamine,
      two aminolipids, and five unknown lipids. On the basis of phenotypic features,
      and the result of 16S rRNA gene sequence analysis, strain CP32(T) (=KCTC 23835(T)
      =JCM 18454(T)) represents a novel species of the genus Winogradskyella, for which
      the name Winogradskyella jejuensis sp. nov. is proposed.

PMID- 23124764
TI  - Genotypic diversity, antibiotic resistance and bacteriocin production of
      enterococci isolated from rhizospheres.
AB  - This study aimed to identify and to characterize rhizospheric-derived
      enterococci. The results showed the prevalence of Enterococcus faecium species
      (97%) vs. Enterococcus durans (3%). Susceptibility testing for antibiotics showed
      a low percentage of resistance to erythromycin (3.2%) and tetracycline (11.2%),
      and intermediate resistance to vancomycin (6.5%). Nevertheless, a high proportion
      of bacteriocin production was recorded. Furthermore, PCR detection of antibiotic
      resistance and bacteriocin production-encoding genes was investigated. Pulsed
      field gel electrophoresis typing (PFGE) showed a great variability of enterococci
      in the rhizosphere. Moreover, mutilocus-sequence-typing analysis (MLST) revealed
      the identification of three new sequence types (STs), which were registered as
      ST613, ST614 and ST615.

PMID- 23124766
TI  - Impact of chloramination on the development of laboratory-grown biofilms fed with
      filter-pretreated groundwater.
AB  - This study evaluated the continuous impact of monochloramine disinfection on
      laboratory-grown biofilms through the characterization of biofilm architecture
      and microbial community structure. Biofilm development and disinfection were
      achieved using CDC (Centers for Disease Control and Prevention) biofilm reactor
      systems with polyvinyl chloride (PVC) coupons as the substratum and sand filter
      pretreated groundwater as the source of microbial seeding and growth nutrient.
      After 2 weeks of growth, the biofilms were subjected to chloramination for 8 more
      weeks at concentrations of 7.5+/-1.4 to 9.1+/-0.4 mg Cl2 L(-1). Control reactors
      received no disinfection during the development of biofilms. Confocal laser
      scanning microscopy and image analysis indicated that chloramination could lead
      to 81.4-83.5% and 86.3-95.6% reduction in biofilm biomass and thickness,
      respectively, but could not eliminate biofilm growth. 16S rRNA gene terminal
      restriction fragment length polymorphism analysis indicated that microbial
      community structures between chloraminated and non-chloraminated biofilms
      exhibited different successional trends. 16S rRNA gene pyrosequencing analysis
      further revealed that chloramination could select members of Actinobacteria and
      Acidobacteria as the dominant populations, whereas natural development leads to
      the selection of members of Nitrospira and Bacteroidetes as dominant biofilm
      populations. Overall, chloramination treatment could alter the growth of multi
      species biofilms on the PVC surface, shape the biofilm architecture, and select a
      certain microbial community that can survive or proliferate under chloramination.

PMID- 23124765
TI  - CARD-FISH for environmental microorganisms: technical advancement and future
      applications.
AB  - Fluorescence in situ hybridization (FISH) has become a standard technique in
      environmental microbiology. More than 20 years have passed since this technique
      was first described, and it is currently used for the detection of ribosomal RNA,
      messenger RNA, and functional genes encoded on chromosomes. This review focuses
      on the advancement and applications of FISH combined with catalyzed reporter
      deposition (CARD, also known as tyramide signal amplification or TSA), in the
      detection of environmental microorganisms. Significant methodological
      improvements have been made in CARD-FISH technology, including its combination
      with other techniques and instruments.

PMID- 23124767
TI  - Quantification of left ventricular indices from SSFP cine imaging: impact of real
      world variability in analysis methodology and utility of geometric modeling.
AB  - PURPOSE: To assess the impact of "real-world" practice variation in the process
      of quantifying left ventricular (LV) mass, volume indices, and ejection fraction
      (EF) from steady-state free precession cardiovascular magnetic resonance (CMR)
      images. The utility of LV geometric modeling techniques was also assessed.
      MATERIALS AND METHODS: The effect of short-axis- versus long-axis-derived LV base
      identification, simplified versus detailed endocardial contouring, and visual
      versus automated identification of end-systole were evaluated using CMR images
      from 50 consecutive, prospectively recruited patients. Additionally, the
      performance of six geometric models was assessed. Repeated measurements were
      performed on 25 scans (50%) in order to assess observer variability. RESULTS:
      Simplified endocardial contouring significantly overestimated volumes and
      underestimated EF (-6 +/- 4%, P < 0.0005) compared to detailed contouring. A mean
      difference of -34g (P < 0.0005) was observed between mass measurements made using
      short-axis- versus long-axis-derived LV base positioning. A technique involving
      long-axis LV base identification, signal threshold-based detailed endocardial
      contouring, and automated identification of end-systole had significantly higher
      observer agreement. Geometric models showed poor agreement with conventional
      analysis and high variability. CONCLUSION: Real-world variability in CMR image
      analysis leads to significant differences in LV mass, volume and EF measurements,
      and observer variability. Appropriate reference ranges should be applied. Use of
      geometric models should be discouraged.

PMID- 23124768
TI  - Repression of oxalic acid-mediated mineral phosphate solubilization in
      rhizospheric isolates of Klebsiella pneumoniae by succinate.
AB  - Two strains of Klebsiella (SM6 and SM11) were isolated from rhizospheric soil
      that solubilized mineral phosphate by secretion of oxalic acid from glucose.
      Activities of enzymes for periplasmic glucose oxidation (glucose dehydrogenase)
      and glyoxylate shunt (isocitrate lyase and glyoxylate oxidase) responsible for
      oxalic acid production were estimated. In presence of succinate, phosphate
      solubilization was completely inhibited, and the enzymes glucose dehydrogenase
      and glyoxylate oxidase were repressed. Significant activity of isocitrate lyase,
      the key enzyme for carbon flux through glyoxylate shunt and oxalic acid
      production during growth on glucose suggested that it could be inducible in
      nature, and its inhibition by succinate appeared to be similar to catabolite
      repression.

PMID- 23124769
TI  - Differential expression profiles of microRNAs as potential biomarkers for the
      early diagnosis of esophageal squamous cell carcinoma.
AB  - Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies
      worldwide. To reduce the high morbidity and mortality of the disease, sensitive
      and specific biomarkers for early detection are urgently needed. Tumor-specific
      microRNAs (miRNAs) seem to be potential biomarkers for the early diagnosis and
      treatment of cancer. In this study, differentially expressed miRNAs in tumor
      tissues and adjacent non-tumor tissues were detected by miRNA microarrays. Stem
      loop real-time reverse transcription PCR was conducted to verify the candidate
      miRNAs discovered by microarray analysis. The data showed that hsa-miR-338-3p,
      hsa-miR-218 and hsa-miR-139-5p were downregulated in tumor tissues compared with
      adjacent non-tumor tissues, while hsa-miR-183, hsa-miR-574-5p, hsa-miR-21* and
      hsa-miR-601 were upregulated in tumor tissues. Multiple regression analysis
      revealed the aberrant expression of hsa-miR-338-3p, hsa-miR-139-5p, hsa-miR-574
      5p and hsa-miR-601 increased the risk of esophageal cancer. Furthermore, we found
      hsa-miR-21* was significantly increased in heavy drinking patients. Therefore,
      there is a set of differentially expressed miRNAs in esophageal cancer which may
      be associated with the incidence and development of ESCC. Differential expression
      profiles of miRNAs in ESCC may be promising biomarkers for the early screening of
      high-risk populations and early detection.

PMID- 23124770
TI  - Cortical projections to the superior colliculus in tree shrews (Tupaia
      belangeri).
AB  - The visuomotor functions of the superior colliculus depend not only on direct
      inputs from the retina, but also on inputs from neocortex. As mammals vary in the
      areal organization of neocortex, and in the organization of the number of visual
      and visuomotor areas, patterns of corticotectal projections vary. Primates in
      particular have a large number of visual areas projecting to the superior
      colliculus. As tree shrews are close relatives of primates, and they are also
      highly visual, we studied the distribution of cortical neurons projecting to the
      superior colliculus by injecting anatomical tracers into the colliculus. Since
      projections from visuotopically organized visual areas are expected to match the
      visuotopy of the superior colliculus, injections at different retinotopic
      locations in the superior colliculus provide information about the locations and
      organization of topographic areas in extrastriate cortex. Small injections in the
      superior colliculus labeled neurons in locations within areas 17 (V1) and 18 (V2)
      that are consistent with the known topography of these areas and the superior
      colliculus. In addition, the separate locations of clusters of labeled cells in
      temporal visual cortex provide evidence for five or more topographically
      organized areas. Injections that included deeper layers of the superior
      colliculus also labeled neurons in medial frontal cortex, likely in premotor
      cortex. Only occasional labeled neurons were observed in somatosensory or
      auditory cortex. Regardless of tracer injection location, we found that, unlike
      primates, a substantial projection to the superior colliculus from posterior
      parietal cortex is not a characteristic of tree shrews.

PMID- 23124771
TI  - Region-specific causal mechanism in the effects of ammonia on cerebral glucose
      metabolism in the rat brain.
AB  - Ammonia, which is considered to be the main agent responsible for hepatic
      encephalopathy, inhibits oxidative glucose metabolism in the brain. However, the
      effects of ammonia on cerebral glucose metabolism in different brain regions
      remains unclear. To clarify this issue, we added ammonia directly to fresh rat
      brain slices and measured its effects on glucose metabolism. Dynamic positron
      autoradiography with [(18)F]2-fluoro-2-deoxy-D-glucose and 2-(4-iodophenyl)-3-(4
      nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium (WST-1) colorimetric assay
      revealed that ammonia significantly increased the cerebral glucose metabolic rate
      and depressed mitochondrial function, as compared to the unloaded control in each
      of the brain regions examined (cerebral cortex, striatum, and cerebellum),
      reflecting increased glycolysis that compensates for the decrease in aerobic
      metabolism. Pre-treatment with (+)-5-methyl-10,11-dihydro-5H
      dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801), a N-methyl-D
      aspartate (NMDA) receptor antagonist, significantly attenuated these changes
      induced by ammonia in cerebellum, but not in cerebral cortex or striatum. The
      addition of ammonia induced an increase in cyclic guanosine monophosphate (cGMP)
      levels in cerebellum, but not in cerebral cortex or striatum, reflecting the
      activation of the NMDA receptor-nitric oxide-cGMP pathway. These results
      suggested that NMDA receptor activation is responsible for the impairment of
      glucose metabolism induced by ammonia specifically in cerebellum.

PMID- 23124772
TI  - Changes in distribution of cell wall polysaccharides in floral and fruit
      abscission zones during fruit development in tomato (Solanum lycopersicum).
AB  - After fruit development has been triggered by pollination, the abscission zone
      (AZ) in the pedicel strengthens its adhesion to keep the fruit attached.
      Unpollinated flowers are shed at their respective AZs, whereas an enlargement of
      the same tissue is observed in pollinated flowers. After the fruit has developed
      and is fully ripened, shedding occurs easily at the AZ, indicating an
      acceleration of abscission. Cell wall degradation and synthesis may play
      important roles in these processes; however, little is understood. In this
      report, we have visualized changes in polysaccharide distribution in the AZs of
      pollinated versus unpollinated flowers and in the ripened fruits using
      immunohistochemistry. During floral abscission, a large increase was observed in
      LM15 labeling of xyloglucan specifically at the AZ in the abscising pedicel. LM5
      and LM6 labeling of galactan and arabinan, respectively, also increased-LM5
      throughout the pedicel and LM6 at the basal side of the AZ. The results suggest
      that xyloglucan, pectic galactan and arabinan play key roles in the abscission
      process. During fruit abscission, unlike in floral abscission, no AZ-specific
      cell wall polysaccharide deposition was observed; however, high autofluorescence
      was seen in the AZ of over-ripe fruit pedicels, suggesting secondary cell wall
      synthesis and lignification of the AZ prior to fruit abscission.

PMID- 23124773
TI  - Mortality of 403 patients with mood disorders 48 to 52 years after their
      psychiatric hospitalisation.
AB  - The purpose is to analyse differences in mortality among patients with major
      depressive disorders (MDD), bipolar-II (BP-II), bipolar-I (BP-I) disorders and
      mania with or without minor depressive disorders and to identify risk factors of
      mortality. The sample represents all admissions for depression or mania over 5
      years (1959-1963) to the Psychiatric Hospital of Zurich University, serving a
      large area. 403 patients were included and followed up every 5 years until 1985;
      thereafter, mortality data were collected repeatedly until 2009 when 352 (87 %)
      patients had died. Standardised mortality ratios (SMRs) were computed and
      survival analyses applied. With the exception of BP-II disorder, the three other
      diagnostic groups showed elevated SMRs. The group with mania had the highest SMR
      for cardiovascular deaths and the group with MDD the highest for deaths by
      suicide. Mortality was also high among patients with late-onset MDD. Across the
      diagnostic spectrum, we found differences in risk factors for mortality, such as
      a family history of suicides and personality type: more anxious patients with MDD
      lived longer, and among patients with BP disorders, more tense (aggressive) types
      had shorter lives. Long-term medication had a protective effect against mortality
      in patients with MDD during years 1-9 and in patients with BP disorders during
      years 1-19 after admission. We found marked differences in causes of death and
      risk factors between subgroups of mood disorders. For the purpose of further
      research, it would be recommendable to distinguish pure mania from bipolar
      disorders.

PMID- 23124775
TI  - Effect of 60 Hz electromagnetic fields on the activity of hsp70 promoter: an in
      vivo study.
AB  - Exposure to EMFs (electromagnetic fields) results in a number of important
      biological changes, including modification of genetic expression. We have
      investigated the effect of 60 Hz sinusoidal EMFs at a magnetic flux density of 80
      MUT on the expression of the luciferase gene contained in a plasmid labelled as
      pEMF (EMF plasmid). This gene construct contains the specific sequences for the
      induction of hsp70 (heat-shock protein 70) expression by EMFs, as well as the
      reporter for the luciferase gene. The pEMF vector was electrotransferred into
      quadriceps muscles of BALB/c mice that were later exposed to EMFs. Increased
      luciferase expression was observed in mice exposed to EMFs 2 h daily for 7 days
      compared with controls (P<0.05). These data along with other reports in the
      literature suggest that EMFs can have far-reaching effects on the genome.

PMID- 23124774
TI  - Do radiographic disease and pain account for why people with or at high risk of
      knee osteoarthritis do not meet physical activity guidelines?
AB  - OBJECTIVE: Knee osteoarthritis (OA) and pain are assumed to be barriers to
      meeting physical activity guidelines, but this has not been formally evaluated.
      The purpose of this study was to determine the proportions of people with and
      those without knee OA and knee pain who meet recommended physical activity levels
      through walking. METHODS: We performed a cross-sectional analysis of community
      dwelling adults from the Multicenter Osteoarthritis Study who had or who were at
      high risk of knee OA. Participants wore a StepWatch activity monitor to record
      steps per day for 7 days. The proportion of participants who met the recommended
      physical activity levels was defined as those accumulating>=150 minutes per week
      at >=100 steps per minute in bouts lasting >=10 minutes. These proportions were
      also determined for those with and those without knee OA, as classified by
      radiography and by severity of knee pain. RESULTS: Of the 1,788 study
      participants (mean+/-SD age 67.2+/-7.7 years, mean+/-SD body mass index 30.7+/
      6.0 kg/m2, 60% women), lower overall percentages of participants with
      radiographic knee OA and knee pain met recommended physical activity levels.
      However, these differences were not statistically significant between those with
      and those without knee OA; 7.3% and 10.1% of men (P=0.34) and 6.3% and 7.8% of
      women (P=0.51), respectively, met recommended physical activity levels.
      Similarly, for those with moderate/severe knee pain and those with no knee pain,
      12.9% and 10.9% of men (P=0.74) and 6.7% and 11.0% of women (P=0.40),
      respectively, met recommended physical activity levels. CONCLUSION: Disease and
      pain have little impact on achieving recommended physical activity levels among
      people with or at high risk of knee OA.

PMID- 23124776
TI  - In situ liver transection with portal vein ligation for rapid growth of the
      future liver remnant in two-stage liver resection.
AB  - BACKGROUND: Portal vein embolization (PVE) has become a standard procedure to
      increase the future liver remnant (FLR) and enable curative resection of
      initially unresectable liver tumours. This study investigated the safety and
      feasibility of a new two-stage liver resection technique that uses in situ liver
      transection (ISLT) and portal vein ligation before completion hepatectomy.
      METHODS: A consecutive series of patients undergoing ISLT and extended right
      hepatectomy between 2009 and 2011 were compared with consecutive patients
      undergoing extended right hepatectomy after PVE. All patients had initially
      unresectable primary or secondary liver tumours, owing to an insufficient FLR
      (liver segments II/III). RESULTS: Fifteen patients who had PVE and seven who
      underwent ISLT before extended right hepatectomy were evaluated. ISLT induced
      rapid growth of the FLR within 3 days, particularly after insufficient PVE, from
      a mean(s.d.) of 293(58) ml to 477(85) ml, corresponding to a volume increase of
      63(29) per cent. All patients who had ISLT underwent completion extended right
      hepatectomy within 8 days (range 4-8 days). CONCLUSION: ISLT is an effective and
      reliable technique to induce rapid growth of the FLR, even in patients with
      insufficient volume increase after PVE.

PMID- 23124777
TI  - Severe cerebral injury in a recipient with twin anemia-polycythemia sequence.
AB  - Twin anemia-polycythemia sequence (TAPS) results from slow intertwin blood
      transfusion through minuscule placental vascular anastomoses and is characterized
      by large intertwin hemoglobin differences in the absence of amniotic fluid
      discordance. The optimal management of TAPS is not clear. We report a case of
      TAPS detected antenatally by Doppler ultrasound examination at 15 + 6 weeks'
      gestation. After counseling, the parents opted for expectant management. Regular
      Doppler measurements were performed and these remained fairly stable. An
      emergency Cesarean section was performed at 34 + 5 weeks following signs of fetal
      distress. The donor twin was severely anemic while the recipient twin had severe
      polycythemia-hyperviscosity syndrome. On day 1, the recipient developed
      respiratory insufficiency and subclinical status epilepticus. Magnetic resonance
      imaging showed a total loss of gray-white matter differentiation as a sign of
      severe diffuse cerebral ischemia and bilateral intra- and extra-axial
      hemorrhages. There was almost complete lack of arterial and venous cerebral blood
      flow. On day 3 intensive care treatment was withdrawn in view of the severity of
      the brain injury. This case report demonstrates that TAPS may lead to severe
      cerebral injury and fatal outcome in the recipient twin, and highlights the
      importance of antenatal Doppler ultrasound monitoring and choice of management.

PMID- 23124778
TI  - Identifying implausible gestational ages in preterm babies with Bayesian mixture
      models.
AB  - Infant birth weight and gestational age are two important variables in obstetric
      research. The primary measure of gestational age used in US birth data is based
      on a mother's recall of her last menstrual period, which has been shown to
      introduce random or systematic errors. To mitigate some of those errors, Oja et
      al., Platt et al., and Tentoni et al. estimated the probabilities of gestational
      ages being misreported under the assumption that the distribution of infant birth
      weights for a true gestational age is approximately Gaussian. From this
      assumption, Oja et al. fitted a three-component mixture model, and Tentoni et al.
      and Platt et al. fitted two-component mixture models. We build on their methods
      and develop a Bayesian mixture model. We then extend our methods using reversible
      jump Markov chain Monte Carlo to incorporate the uncertainty in the number of
      components in the model. We conduct simulation studies and apply our methods to
      singleton births with reported gestational ages of 23-32 weeks using 2001-2008 US
      birth data. Results show that a three-component mixture model fits the birth data
      better for gestational ages reported as 25 weeks or less; and a two-component
      mixture model fits better for the higher gestational ages. Under the assumption
      that our Bayesian mixture models are appropriate for US birth data, our research
      provides useful statistical tools to identify records with implausible
      gestational ages, and the techniques can be used in part of a multiple-imputation
      procedure for missing and implausible gestational ages.

PMID- 23124779
TI  - Association between AKI, recovery of renal function, and long-term outcomes after
      hospital discharge.
AB  - BACKGROUND AND OBJECTIVES: This study aimed to determine if recovery of kidney
      function after AKI modifies the association between AKI during hospitalization
      and adverse outcomes after discharge. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: The effect of renal recovery after AKI was evaluated in a
      population-based cohort study (n=190,714) with participants identified from a
      provincial claims registry in Alberta, Canada, between November 1, 2002 and
      December 31, 2007. AKI was identified by a two-fold increase between prehospital
      and peak in-hospital serum creatinine (SCr). Recovery was assessed using SCr
      drawn closest to 90 days after the AKI event. All-cause mortality and a combined
      renal outcome of sustained doubling of SCr or progression to kidney failure were
      evaluated. RESULTS: Overall, 3.7% of the participants (n=7014) had AKI, 62.7% of
      whom (n=4400) survived 90 days. In the 3231 patients in whom recovery could be
      assessed over a median follow-up of 34 months, 30.8% (n=1268) of AKI survivors
      died and 2.1% (n=85) progressed to kidney failure. Participants who did not
      recover kidney function had a higher risk for mortality and adverse renal
      outcomes when AKI participants who recovered to within 25% of baseline SCr were
      used as the reference group (adjusted mortality hazard ratio (HR), 1.26; 95%
      confidence interval, 1.10, 1.43) (adjusted renal outcomes HR, 4.13; 95%
      confidence interval, 3.38, 5.04). Mortality HR was notably higher when
      participants failed to recover within 55% of baseline. CONCLUSIONS: Renal
      recovery after AKI is associated with a lower risk of death or adverse renal
      outcomes after hospital discharge.

PMID- 23124780
TI  - Associations of serum skeletal alkaline phosphatase with elevated C-reactive
      protein and mortality.
AB  - BACKGROUND AND OBJECTIVES: Higher serum total alkaline phosphatase (AP) levels
      are associated with increased serum C-reactive protein (CRP) levels and mortality
      in the general and CKD populations. It is unclear to what extent these
      associations are related to bone disease. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: In a nationally representative sample of 10,707 adult participants
      from the 1999-2004 National Health and Nutrition Examination Survey, serum
      nonskeletal AP levels were estimated from the measured serum skeletal and total
      AP levels. The associations of serum skeletal AP and nonskeletal AP levels with
      elevated serum CRP concentrations (>3 mg/L) and mortality were examined in
      multivariable models. RESULTS: Skeletal AP was not associated with elevated CRP
      (for each doubling in non-CKD: odds ratio [OR], 1.00; 95% confidence interval
      [95% CI], 0.90-1.11; in CKD: OR, 1.19; 95% CI, 0.83-1.70) or mortality (for each
      doubling in non-CKD: hazard ratio [HR], 1.10; 95% CI, 0.94-1.29; in CKD: HR,
      0.98; 95% CI, 0.75-1.28). In contrast, nonskeletal AP was associated with
      elevated CRP (for each doubling in non-CKD: OR, 4.51; 95% CI, 3.80-5.35; in CKD:
      OR, 5.98; 95% CI, 3.40-10.51). Nonskeletal AP was associated with mortality in
      non-CKD (for each doubling: HR, 1.96; 95% CI, 1.37-2.80) but not in CKD (for each
      doubling: HR, 0.92; 95% CI, 0.51-1.67) (interaction P=0.03). CONCLUSIONS: Bone
      disease is unlikely to account for the known associations of serum total AP with
      increased inflammation and mortality.

PMID- 23124782
TI  - Randomized clinical trial of the iron-based phosphate binder PA21 in hemodialysis
      patients.
AB  - BACKGROUND AND OBJECTIVES: A dose-finding study was undertaken to investigate the
      efficacy of PA21, a novel polynuclear iron(III)-oxyhydroxide phosphate binder.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a randomized, active
      controlled, multicenter, open-label study at 50 clinical sites in Europe and the
      United States, hemodialysis patients were randomized to PA21 at dosages of 1.25,
      5.0, 7.5, 10.0, or 12.5 g/d or sevelamer-HCl 4.8 g/d for 6 weeks. The primary
      efficacy endpoint was the change in serum phosphorus concentration from baseline.
      RESULTS: There were 154 participants who were randomized and received the study
      drug. All groups except PA21 1.25 g/d showed a significant decrease in serum
      phosphorus. Mean decreases in serum phosphorus in PA21 10 g/d and 12.5 g/d were 
      2.00+/-1.71 mg/dl and -1.69+/-1.81 mg/dl, respectively. A similar decrease to
      sevelamer-HCl (-1.06+/-1.35 mg/dl) was seen with PA21 5.0 g/d (-1.08+/-2.12
      mg/dl) and 7.5 g/d (-1.25+/-1.21 mg/d). Overall, 60.9% of participants randomized
      to PA21 and 57.7% randomized to sevelamer-HCl reported >=1 adverse event. The
      most frequent adverse events were hypophosphatemia (18.0%) and discolored feces
      (11.7%) for the pooled PA21 dose groups, and diarrhea, hypophosphatemia, and
      hypotension (each 11.5%) for sevelamer-HCl. Discontinuation due to adverse events
      occurred at a similar rate in PA21-treated (21.1%) and sevelamer-HCl-treated
      (23.1%) participants. CONCLUSIONS: PA21 5-12.5 g/d significantly reduces serum
      phosphorus in hemodialysis patients. The 5 g/d and 7.5 g/d dosages showed similar
      efficacy to 4.8 g/d of sevelamer-HCl. The adverse events rate was similar for
      PA21 and sevelamer-HCl.

PMID- 23124781
TI  - Change in cardiac geometry and function in CKD children during strict BP control:
      a randomized study.
AB  - BACKGROUND AND OBJECTIVES: Left ventricular hypertrophy (LVH) and abnormal
      systolic function are present in a high proportion of children with CKD. This
      study evaluated changes in left ventricular (LV) geometry and systolic function
      in children with mild to moderate CKD as an ancillary project of the Effect of
      Strict Blood Pressure Control and ACE Inhibition on Progression of Chronic Renal
      Failure in Pediatric Patients trial. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: Echocardiograms and ambulatory BP monitoring were performed at
      baseline and at 1- or 2-year follow-up in 84 patients with CKD and 24-hour mean
      BP above the 50th percentile and/or receiving fixed high-dose angiotensin
      converting enzyme inhibition and randomized to conventional or intensified BP
      control. RESULTS: LVH prevalence decreased from 38% to 25% (P<0.05). Changes in
      LV mass index (LVMI) were restricted to patients with LVH at baseline (-7.9
      g/m(2.7); P<0.02). Changes in LVMI were independent of randomization, reduction
      in BP, hemoglobin, and estimated GFR. A significant increase in midwall
      fractional shortening was observed in the total cohort (P<0.05), and was greater
      in the intensified group compared with the conventional BP control group (12%+/
      1.9% versus 8%+/-1.5%; P=0.05). In multivariate analysis, improvement in
      myocardial function was associated with reduction in BP (r=-0.4; P<0.05),
      independently of LVMI reduction. CONCLUSIONS: In children with CKD, angiotensin
      converting enzyme inhibition with improved BP control, LVH regression, and
      improved systolic function was observed within 12 months. Lowering BP to the low
      normal range led to a slightly more marked improvement in myocardial function but
      not in LVMI.

PMID- 23124783
TI  - Effect of hemodiafiltration on quality of life over time.
AB  - BACKGROUND AND OBJECTIVES: It is unclear if hemodiafiltration leads to a better
      quality of life compared with hemodialysis. It was, therefore, the aim of this
      study to assess the effect of hemodiafiltration on quality of life compared with
      hemodialysis in patients with ESRD. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: This study analyzed the data of 714 patients with a median follow
      up of 2 years from the Convective Transport Study. The patients were enrolled
      between June of 2004 and December of 2009. The Convective Transport Study is a
      randomized controlled trial on the effect of online hemodiafiltration versus low
      flux hemodialysis on all-cause mortality. Quality of life was assessed with the
      Kidney Disease Quality of Life-Short Form. This questionnaire provides data for a
      physical and mental composite score and describes kidney disease-specific quality
      of life in 12 domains. The domains have scales from 0 to 100. RESULTS: There were
      no significant differences in changes in health-related quality of life over time
      between patients treated with hemodialysis (n=358) or hemodiafiltration (n=356).
      The quality of life domain patient satisfaction declined over time in both
      dialysis modalities (hemodialysis: -2.5/yr, -3.4 to -1.5, P<0.001;
      hemodiafiltration: -1.4/yr, -2.4 to -0.5, P=0.004). CONCLUSIONS: Compared with
      hemodialysis, hemodiafiltration had no significant effect on quality of life over
      time.

PMID- 23124784
TI  - Effect of the dialysis fluid buffer on peritoneal membrane function in children.
AB  - BACKGROUND AND OBJECTIVES: Double-chamber peritoneal dialysis fluids exert less
      toxicity by their neutral pH and reduced glucose degradation product content. The
      role of the buffer compound (lactate and bicarbonate) has not been defined in
      humans. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A multicenter randomized
      controlled trial in 37 children on automated peritoneal dialysis was performed.
      After a 2-month run-in period with conventional peritoneal dialysis fluids,
      patients were randomized to neutral-pH, low-glucose degradation product
      peritoneal dialysis fluids with 35 mM lactate or 34 mM bicarbonate content.
      Clinical and biochemical monitoring was performed monthly, and peritoneal
      equilibration tests and 24-hour clearance studies were performed at 0, 3, 6, and
      10 months. RESULTS: No statistically significant difference in capillary blood
      pH, serum bicarbonate, or oral buffer supplementation emerged during the study.
      At baseline, peritoneal solute equilibration and clearance rates were similar.
      During the study, 4-hour dialysis to plasma ratio of creatinine tended to
      increase, and 24-hour dialytic creatinine and phosphate clearance increased with
      lactate peritoneal dialysis fluid but not with bicarbonate peritoneal dialysis
      fluid. Daily net ultrafiltration, which was similar at baseline (lactate
      fluid=5.4+/-2.6 ml/g glucose exposure, bicarbonate fluid=4.9+/-1.9 ml/g glucose
      exposure), decreased to 4.6+/-1.0 ml/g glucose exposure in the lactate peritoneal
      dialysis fluid group, whereas it increased to 5.1+/-1.7 ml/g glucose exposure in
      the bicarbonate content peritoneal dialysis fluid group (P=0.006 for
      interaction). CONCLUSIONS: When using biocompatible peritoneal dialysis fluids,
      equally good acidosis control is achieved with lactate and bicarbonate buffers.
      Improved long-term preservation of peritoneal membrane function may, however, be
      achieved with bicarbonate-based peritoneal dialysis fluids.

PMID- 23124785
TI  - Multiple pregnancies in CKD patients: an explosive mix.
AB  - BACKGROUND AND OBJECTIVES: CKD and multiple pregnancies bear important risks for
      pregnancy outcomes. The aim of the study was to define the risk for adverse
      pregnancy-related outcomes in multiple pregnancies in CKD patients in comparison
      with a control group of "low-risk" multiple pregnancies. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: The study was performed in the Maternal Hospital of
      the University of Turin, Italy. Of 314 pregnancies referred in CKD (2000-2011),
      20 were multiple (15 twin deliveries). Control groups consisted of 379 low-risk
      multiple pregnancies (314 twin deliveries) and 19 (15 twin deliveries) cases with
      hypertension-collagen diseases. Baseline data and outcomes were compared by
      univariate and logistic regression analyses. RESULTS: The prevalence of multiple
      pregnancies was relatively high in the CKD population (6.4%); all referred cases
      were in early CKD stages (I-II); both creatinine (0.68 to 0.79 mg/dl; P=0.010)
      and proteinuria (0.81 to 3.42 g/d; P=0.041) significantly increased from referral
      to delivery. No significant difference in demographic data at baseline was found
      between cases and low-risk controls. CKD was associated with higher risk of
      adverse pregnancy outcomes versus low-risk twin pregnancies. Statistical
      significance was reached for preterm delivery (<34 weeks: 60% vs 26.4%; P=0.005;
      <32 weeks: 53.3% vs 12.7%; P<0.001), small for gestational age babies (28.6% vs
      8.1%; P<0.001), need for Neonatal Intensive Care Unit (60% vs 12.7%; P<0.001),
      weight discordance between twins (40% vs 17.8%; P=0.032), and neonatal and
      perinatal mortality (6.6% vs 0.8%; P=0.032). CONCLUSION: This study suggests that
      maternal-fetal risks are increased in multiple pregnancies in the early CKD
      stages.

PMID- 23124786
TI  - Effect of oral anabolic steroid on muscle strength and muscle growth in
      hemodialysis patients.
AB  - BACKGROUND AND OBJECTIVES: Sarcopenia is common in hemodialysis patients. This
      study examined whether the anabolic steroid oxymetholone improves muscle mass and
      handgrip strength in hemodialysis patients and possible mechanisms that might
      engender such changes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Forty-three
      eligible hemodialysis patients were randomly assigned to ingest oxymetholone or
      placebo for 24 weeks. Body composition, handgrip strength, and quality of life
      were measured during the study. Muscle biopsies were performed and analyzed for
      mRNA levels for myostatin, IGF-I, IGF binding proteins, and myosin heavy chains
      and protein expression. Muscle fiber types and diameter were assessed by reduced
      nicotinamide-adenine dinucleotide staining. RESULTS: There was a significantly
      greater increase in fat-free mass and handgrip strength and decrease in fat mass
      in the oxymetholone compared with the placebo group. Moreover, compared with
      baseline values, patients given oxymetholone exhibited an increase in fat-free
      mass, handgrip strength, physical functioning scores, and type I muscle fiber
      cross-sectional area and a decrease in fat mass, whereas patients receiving
      placebo did not undergo changes. There was a significantly greater increase in
      muscle mRNA levels for myosin heavy chain 2*, IGF-I, and IGF-II receptor with
      oxymetholone treatment than placebo. Liver enzyme rose significantly in the
      oxymetholone group, but the number of values greater than three times the upper
      limit of normal were not different between these groups. CONCLUSIONS: In
      hemodialysis patients, ingesting oxymetholone was associated with an increase in
      fat-free mass, handgrip strength, and muscle mRNA levels for several growth
      factors and a decrease in fat mass, but it also induced liver injury.

PMID- 23124787
TI  - Association of physical activity with survival among ambulatory patients on
      dialysis: the Comprehensive Dialysis Study.
AB  - BACKGROUND AND OBJECTIVES: Despite high mortality and low levels of physical
      activity (PA) among patients starting dialysis, the link between low PA and
      mortality has not been carefully evaluated. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: The Comprehensive Dialysis Study was a prospective cohort study
      that enrolled patients who started dialysis between June 2005 and June 2007 in a
      random sample of dialysis facilities in the United States. The Human Activity
      Profile (HAP) was administered to estimate PA among 1554 ambulatory enrolled
      patients in the Comprehensive Dialysis Study. Patients were followed until death
      or September 30, 2009, and the major outcome was all-cause mortality. RESULTS:
      The average age was 59.8 (14.2) years; 55% of participants were male, 28% were
      black, and 56% had diabetes mellitus. The majority (57.3%) had low fitness
      estimated from the HAP score. The median follow-up was 2.6 (interquartile range,
      2.2-3.1) years. The association between PA and mortality was linear across the
      range of scores (1-94). After multivariable adjustment, lower adjusted activity
      score on the HAP was associated with higher mortality (hazard ratio, 1.30; 95%
      confidence interval, 1.23-1.39 per 10 points). Patients in the lowest level of
      fitness experienced a 3.5-fold (95% confidence interval, 2.54-4.89) increase in
      risk of death compared with those with average or above fitness. CONCLUSIONS: Low
      levels of PA are strongly associated with mortality among patients new to
      dialysis. Interventions aimed to preserve or enhance PA should be prospectively
      tested.

PMID- 23124788
TI  - The USRDS: what you need to know about what it can and can't tell us about ESRD.
AB  - This article summarizes the administrative structure underlying the Unites States
      Renal Data System (USRDS); summarizes incidence, prevalence, patient
      characteristics, and treatment modalities; and describes data regarding clinical
      indicators and preventive care, hospitalization, survival, and costs. The USRDS
      recently instituted a comprehensive assessment system to characterize the
      transition to the new Centers for Medicare & Medicaid Services Prospective
      Payment System, which bundles into a single payment several integral components
      of dialysis care. This challenging initiative will be an important component of
      future USRDS Annual Data Reports. The main strengths of the USRDS are its size
      and representativeness, nearly complete inclusion of the US end-stage renal
      disease population, and linkage to Medicare claims. Limitations include lack of
      continuous validation of its methods, lack of complete comorbidity and laboratory
      data at registration, an initial survival bias, and lack of accuracy of cause-of
      death reporting.

PMID- 23124789
TI  - Time to secondary progression in patients with multiple sclerosis who were
      treated with first generation immunomodulating drugs.
AB  - BACKGROUND: It is currently unknown whether early immunomodulatory treatment in
      relapsing-remitting MS (RRMS) can delay the transition to secondary progression
      (SP). OBJECTIVE: To compare the time interval from onset to SP in patients with
      RRMS between a contemporary cohort, treated with first generation disease
      modifying drugs (DMDs), and a historical control cohort. METHODS: We included a
      cohort of contemporary RRMS patients treated with DMDs, obtained from the Swedish
      National MS Registry (disease onset between 1995-2004, n = 730) and a historical
      population-based incidence cohort (onset 1950-64, n = 186). We retrospectively
      analyzed the difference in time to SP, termed the "period effect" within a 12
      year survival analysis, using Kaplan-Meier and Cox regression analysis. RESULTS:
      We found that the "period" affected the entire severity spectrum. After adjusting
      for onset features, which were weaker in the contemporary material, as well as
      the therapy initiation time, the DMD-treated patients still exhibited a longer
      time to SP than the controls (hazard ratios: men, 0.32; women, 0.53). CONCLUSION:
      Our results showed there was a longer time to SP in the contemporary subjects
      given DMD. Our analyses suggested that this effect was not solely driven by the
      inclusion of benign cases, and it was at least partly due to the long-term
      immunomodulating therapy given.

PMID- 23124791
TI  - Mesenchymal stem cells as treatment for MS - progress to date.
AB  - The unmet need for therapies capable of repairing the central nervous system
      (CNS) damage occurring in many diseases including multiple sclerosis (MS) has
      sparked the interest of the neurological community for stem cell-based therapies.
      An exhaustive amount of preclinical data has shown that the intravenous
      administration of mesenchymal stem cells (MSC), a subset of progenitor cells
      isolated from many mesodermal tissues, effectively ameliorates experimental
      autoimmune encephalomyelitis (EAE), a model of MS, through the release of anti
      inflammatory and neuroprotective molecules. Based on these results, several small
      pilot clinical trials in subjects with advanced MS have demonstrated that MSC
      administration is safe and provided an early signal of clinical effectiveness.
      The current aim of clinicians and scientists interested in the development of MSC
      based strategies for the treatment of MS is to have the ultimate demonstration in
      large clinical trials that MSC can inhibit CNS inflammation and foster tissue
      repair as realized clinically, with functional recovery, or visualized by
      magnetic resonance imaging (MRI).

PMID- 23124790
TI  - Co-occurrence of two cases of progressive multifocal leukoencephalopathy in a
      natalizumab "infusion group".
AB  - We observed two cases of progressive multifocal leukoencephalopathy (PML) that
      occurred in the same "infusion group". The group consisted of four patients with
      relapsing-remitting multiple sclerosis (RRMS) who had been treated with
      natalizumab (NAT) in the same medical practice for more than four years at the
      same times and in the same room, raising concerns about viral transmission
      between members of the infusion group. DNA amplification and sequence comparison
      of the non-coding control region (NCCR) of JC virus (JCV) present in
      cerebrospinal fluid (CSF) samples from PML patients #1 and #2 revealed that the
      amplified JCV sequences differed from the JCV archetype. The NCRR of the viral
      DNA was unique to each patient, arguing against the possibility of viral
      transmission between patients. Statistical considerations predict that similar co
      occurrences of PML are likely to happen in the future. 

PMID- 23124792
TI  - Saliva levels of 3-methoxy-4-hydroxyphenylglycol and clinical efficacy of
      mirtazapine or selective serotonin reuptake inhibitors in patients with major
      depression.
AB  - OBJECTIVE: This study compared saliva levels of 3-methoxy-4-hydroxyphenylglycol
      (sMHPG) in patients with major depressive disorder (MDD) to levels in healthy
      controls and explored whether sMHPG levels in patients with MDD were a predictive
      marker for antidepressant efficacy. METHODS: sMHPG levels were compared in 53
      patients with MDD and 275 age-matched healthy controls. Patients' depressive
      symptoms were assessed by the 17-item Hamilton Rating Scale for Depression at
      baseline and 4 weeks after treatment with selective serotonin reuptake inhibitors
      (SSRIs, n = 23) or mirtazapine (n = 30), followed by saliva sampling. The
      mirtazapine group included nine patients who had been treated with an SSRI for
      more than 4 weeks without any improvement. sMHPG levels were measured by gas
      chromatography-mass spectrometry. RESULTS: sMHPG levels in MDD patients were
      significantly higher than in controls. The responder rate to drug treatment at 4
      weeks was 62% for mirtazapine (13/21), 57% for SSRIs (13/23), and 89% (8/9) for
      SSRI plus mirtazapine. sMHPG at baseline in 13 responders treated with SSRIs, but
      not mirtazapine, was significantly higher than that in non-responder group and
      showed consequent reduction 4 weeks after treatment. The area under the receiver
      operating characteristic (ROC) curves of sMHPG for discrimination of SSRI
      responders and non-responders was 0.86 +/- 0.10 (95% confidence interval: 0.64
      1.0, p = 0.005). In contrast, the ROC curve of sMHPG levels for discrimination of
      mirtazapine responders and non-responders was not significant. Adjunctive
      treatment with mirtazapine to SSRI non-responders was effective, regardless of
      baseline sMHPG levels. CONCLUSION: sMHPG in patients with MDD was higher than in
      healthy controls. High baseline sMHPG levels in patients with MDD maybe a
      predictive marker for SSRI response.

PMID- 23124793
TI  - Methionine-101 from one strain of H5N1 NS1 protein determines its IFN
      antagonizing ability and subcellular distribution pattern.
AB  - Influenza A virus NS1 protein has developed two main IFN-antagonizing mechanisms
      by inhibiting retinoic-acid-inducible gene I (RIG-I) signal transduction, or by
      suppressing cellular pre-mRNA processing through binding to cleavage and
      polyadenylation specific factor 30 (CPSF30). However, the precise effects of NS1
      on suppressing type I IFN induction have not been well characterized. Here we
      report that compared with PR/8/34 NS1, which is localized partially in the
      cytoplasm and has strong IFN-antagonizing ability via specifically inhibiting IFN
      beta promoter activity, H5N1 NS1 has strikingly different characteristics. It
      mainly accumulates in the nucleus of transfected cells and exerts rather weak IFN
      counteracting ability through suppression of the overall gene expression. The
      M101I mutation of H5N1 NS1, namely H5-M101I, fully reversed its functions. H5
      M101I gained the ability to specifically inhibit IFN-beta promoter activity,
      translocate to the cytoplasm, and release CPSF30. The previously reported NES
      (nuclear export signal) (residues 138-147) was unable to lead H5N1 NS1 to
      translocate. This suggests that other residues may serve as a potent NES.
      Findings indicated that together with leucine-100, methionine-101 enhanced the
      regional NES. In addition, methionine-101 was the key residue for the NS1-CPSF30
      interaction. This study reveals the importance of methionine-101 in the influenza
      A virus life cycle and may provide valuable information for antiviral strategies.

PMID- 23124794
TI  - MRI can reveal metabolic changes in lily bulbs in vivo during dormancy release.
AB  - The factors influencing dormancy release in lily bulbs strongly affect
      commercialization success, but the mechanism of dormancy release is still
      unclear. Magnetic resonance imaging (MRI) can detect changes in morphology and
      water status in a living plant bulb and aid in investigating release factors. To
      evaluate whether MRI could be used to detect intra-bulb metabolic changes during
      the dormant period in Oriental Lilies (Lilium 'Sorbonne'), a series of MRI and
      sugar concentration measurements were performed weekly on bulbs stored for 11
      weeks at 4 degrees C. The image quality of intra-bulb structure obtained using T
      (1)-weighted imaging was superior to that obtained using T (2)-weighted imaging
      and had a higher signal-to-noise ratio (0.97 +/- 0.01). Magnetization transfer
      ratio values for the bud and basal plate declined during the first eight weeks of
      cold storage (P>0.05), and were well correlated with concentration of soluble
      sugar in the bud (R (2)=0.95) and basal plate (R (2)=0.93). Thus, MRI can serve
      as a valuable tool for observation and analysis of dynamic morphological and
      metabolic changes in vivo during dormancy release. This information is
      potentially useful as a guide in the improvement of horticultural product
      quality.

PMID- 23124795
TI  - The role of maize root size in phosphorus uptake and productivity of maize/faba
      bean and maize/wheat intercropping systems.
AB  - Interspecific root/rhizosphere interactions affect phosphorus (P) uptake and the
      productivity of maize/faba bean and maize/wheat intercropping systems. The aim of
      these experiments was to determine whether manipulation of maize root growth
      could improve the productivity of the two intercropping systems. Two near
      isogenic maize hybrids (the larger-rooted T149 and smaller-rooted T222) were
      intercropped with faba bean and wheat, under conditions of high- and low-P
      availability. The larger-rooted T149 showed greater competitive ability than the
      smaller-rooted T222 in both maize/faba bean and maize/wheat intercropping
      systems. The higher competitive ability of T149 improved the productivity of the
      maize/faba bean intercropping system in P-sufficient conditions. In maize/wheat
      intercropping systems, root growth, shoot biomass, and P uptake of maize were
      inhibited by wheat, regardless of the P-supply. Compared with T222, the larger
      rooted T149 suffered less in the intercropping systems. The total biomass of the
      maize/wheat intercropping system was higher for wheat/T149 than for wheat/T222
      under low-P conditions. These data suggested that genetic improvement of maize
      root size could enhance maize growth and its ability to compete for P resources
      in maize/faba bean and maize/wheat intercropping systems. In addition, depending
      on the P availability, larger maize roots could increase the productivity of
      intercropping systems.

PMID- 23124796
TI  - Progression and prospects of translational medicine in China.

PMID- 23124797
TI  - A remarkable switch from a diamination to a hydrohydrazination catalyst and
      observation of an unprecedented catalyst resting state.

PMID- 23124800
TI  - Echogenic splenic lesions in a child with type B Niemann-Pick disease.
AB  - We report the case of a 15-year-old boy with Niemann-Pick disease type B with
      characteristic sonographic findings of splenic involvement. There were multiple
      well-defined echogenic nodular lesions within the spleen parenchyma, and these
      lesions were surrounded by ring-like blood flow on color Doppler imaging. Most of
      the patients with Niemann-Pick disease type B are children and they undergo
      repeated imaging studies. Therefore, familiarity with sonographic findings of the
      disease is required.

PMID- 23124798
TI  - Factors associated with depressive symptoms in the early postpartum period among
      women with recent gestational diabetes mellitus.
AB  - Women with gestational diabetes mellitus (GDM) have a substantial risk of
      subsequently developing type 2 diabetes. This risk may be mitigated by engaging
      in healthy eating, physical activity, and weight loss when indicated. Since
      postpartum depressive symptoms may impair a woman's ability to engage in
      lifestyle changes, we sought to identify factors associated with depressive
      symptoms in the early postpartum period among women with recent GDM. The
      participants are part of the baseline cohort of the TEAM GDM (Taking Early Action
      for Mothers with Gestational Diabetes Mellitus) study, a one-year randomized
      trial of a lifestyle intervention program for women with a recent history of GDM,
      conducted in Boston, Massachusetts between June 2010 and September 2012. We
      administered the Edinburgh Postnatal Depression Scale (EPDS) at 4-15 weeks
      postpartum to women whose most recent pregnancy was complicated by GDM (confirmed
      by laboratory data or medical record review). An EPDS score >=9 indicated
      depressive symptoms. We measured height and thyroid stimulating hormone, and
      administered a questionnaire to collect demographic data and information about
      breastfeeding and sleep. We calculated body mass index (BMI) using self-reported
      pre-pregnancy weight and measured height. We reviewed medical records to obtain
      data about medical history, including history of depression, mode of delivery,
      and insulin use during pregnancy. We conducted bivariable analyses to identify
      correlates of postpartum depressive symptoms, and then modeled the odds of
      postpartum depressive symptoms using multivariable logistic regression. Our study
      included 71 women (mean age 33 years +/- 5; 59 % White, 28 % African-American, 13
      % Asian, with 21 % identifying as Hispanic; mean pre-pregnancy BMI 30 kg/m(2) +/-
      6). Thirty-four percent of the women scored >=9 on the EPDS at the postpartum
      visit. In the best fit model, factors associated with depressive symptoms at 6
      weeks postpartum included cesarean delivery (aOR 4.32, 95 % CI 1.46, 13.99) and
      gestational weight gain (aOR 1.21 [1.02, 1.46], for each additional 5 lbs
      gained). Use of insulin during pregnancy, breastfeeding, personal history of
      depression, and lack of a partner were not retained in the model. Identifying
      factors associated with postpartum depression in women with GDM is important
      since depression may interfere with lifestyle change efforts in the postpartum
      period. In this study, cesarean delivery and greater gestational weight gain were
      correlated with postpartum depressive symptoms among women with recent GDM
      (Clinicaltrials.gov NCT01158131). 

PMID- 23124799
TI  - Demographic and placement variables associated with overweight and obesity in
      children in long-term foster care.
AB  - Overweight and obesity is a growing problem for children in foster care. This
      study describes the prevalence of overweight and obesity in an urban, ethnic
      minority population of children ages 2-19 in long-term foster care (N = 312) in
      Los Angeles, California. It also investigates whether demographics or placement
      settings are related to high body mass index. The estimates of prevalence of
      overweight/obesity (>=85th percentile) and obesity (>=95th percentile) were
      presented for gender, age, ethnicity, and placement type. Multiple logistic
      regression was used to examine potential associations between demographic and
      placement variables and weight status. The prevalence of overweight/obesity was
      almost 40 % and obesity was 23 % for the study population. Children placed in a
      group home had the highest prevalence of overweight/obesity (60 %) and obesity
      (43 %) compared to other types of placement. Within this study, older children
      (ages 12-19) were more likely to be overweight/obese than normal weight compared
      to children between 2 and 5 years old when controlling for gender, ethnicity and
      placement (OR = 2.10, CI = 1.14-3.87). These findings suggest that older age and
      long-term foster care in general may be risk factors for obesity. Child welfare
      agencies and health care providers need to work together to train caregivers with
      children in long-term foster care in obesity treatment interventions and obesity
      prevention strategies. 

PMID- 23124801
TI  - Antiaromatic hexaphyrins and octaphyrins stabilized by the hydrogen-bonding
      interactions of meso-imidazolyl groups.
AB  - Stable antiaromatic expanded porphyrins were designed by the judicious
      implementation of meso-imidazolyl groups, which cause stabilization through the
      creation of a hydrogen-bonding network that overcomes antiaromatic electronic
      destabilization. Both the [28]hexaphyrin 1 and the [36]octaphyrin 2, which
      contain imidazolyl groups at two opposite meso positions, are shown to be stable
      Huckel antiaromatic species.

PMID- 23124803
TI  - Polar protein transport between apical and basal cells during tobacco early
      embryogenesis.
AB  - KEY MESSAGE : We found that protein trafficking between apical and basal cell can
      be unidirectional, which reveals the different roles of the two cells in the cell
      to-cell communication between them during early embryogenesis. In most angiosperm
      species, asymmetric zygote division results in an apical cell and a basal cell
      that have distinct cell fates. Much has been speculated about possible
      communication between these cell types in relation to their cell fate
      determination. Here, we report on the use of photoactivatable green fluorescent
      protein (PA-GFP) in tobacco to trace intercellular communication between apical
      and basal cells during early embryogenesis. We found that PA-GFP was transported
      between apical and basal cells of a two-celled proembryo, and that protein
      trafficking was unidirectional toward the apical cell, highlighting different
      cell communication roles. Further ultrastructural analysis showed numerous
      plasmodesmata in the walls connecting the apical and basal cells, which may
      provide channels for protein trafficking. Our data show a possible unique method
      of cell-to-cell communication between apical and basal cells during early
      embryogenesis.

PMID- 23124804
TI  - Screening results for subclinical coronary artery calcification in asymptomatic
      individuals in relation to a detailed parental history of premature coronary
      heart disease.
AB  - A parental history of premature coronary heart disease (CHD) is an established
      risk factor for CHD events in descendants. The study aim was to investigate
      whether subclinical coronary artery calcification (CAC) differs between
      asymptomatic individuals (a) without a parental CHD history, (b) with a parental
      history and (c) without knowledge of parental CHD history. The inclusion of
      individuals without knowledge of parental CHD history is a new approach. We also
      differentiated between CHD of mother and father to gain insight into their
      individual contributions. Data was obtained for 4,301 subjects aged 45-75 years
      free of overt CHD from the baseline screening of the population-based Heinz
      Nixdorf Recall study. CAC, measured by electron-beam computed tomography, was
      modeled conducting logistic regressions. Model 1 included family history, Model 2
      was adjusted for age (and gender) and Model 3 added common CHD risk factors. The
      CAC score was dichotomized using the age and sex-specific 75th percentile. The
      odds ratio (OR) for CAC >= age and sex-specific 75th percentile was 1.33 among
      individuals with parental premature CHD history (95 % confidence interval [95
      %CI]: 1.08, 1.63), which did not change after full adjustment (OR 1.40, 95 %CI:
      1.13, 1.74). Individuals with an unknown biological father or mother had a high
      chance of elevated CAC scores (fully adjusted; father: OR 1.38, 95 %CI: 1.01,
      1.90, mother: OR 1.86, 95 %CI: 0.90, 3.84) compared to the reference group. The
      current study showed an association between parental CHD history and CAC
      independent of common CHD risk factors. This association affirms the use of
      parental CHD history in cardiovascular risk assessment among asymptomatic adults
      in routine practice. The observation that individuals who did not know their
      mother or father are prone to increased CAC scores needs further confirmation in
      large scale studies.

PMID- 23124805
TI  - Clinical and transcriptional response to the long-acting interleukin-1 blocker
      canakinumab in Blau syndrome-related uveitis.
AB  - OBJECTIVE: To report on the clinical response to canakinumab in a patient with
      sporadic nucleotide-binding oligomerization domain-containing protein 2 (NOD-2)
      associated pediatric granulomatous arthritis (Blau syndrome) and severe resistant
      panuveitis, and to describe gene expression profile changes throughout such
      treatment. METHODS: A 4-year-old boy was diagnosed as having Blau syndrome on the
      basis of typical clinical features, histologic evidence of noncaseating
      granulomas, and a NOD2 mutation. Ocular involvement was initially controlled by
      topical and oral corticosteroids, but over the years visual impairment and
      complications, such as macular edema and retinal detachment, progressed. Ocular
      disease remained persistently active despite treatment with multiple different
      immunosuppressants; therefore, canakinumab treatment was started. Before and
      during the first 6 months of treatment, the gene expression profile was
      determined each month. RESULTS: Canakinumab treatment was well tolerated and led
      to rapid quiescence of uveitis, which had been continuously active before this
      treatment. Gene expression profiling analysis of the patient's blood prior to
      initiation of interleukin-1 (IL-1) blockade revealed differential expression of
      1,993 transcripts when compared to healthy controls, and among the up-regulated
      transcripts, pathway analysis showed that the predominant network consisted of
      innate immunity-related transcripts. The transcriptional signature of the patient
      overlapped with the transcriptional signature of patients with systemic-onset
      juvenile idiopathic arthritis, and canakinumab treatment led to the normalization
      of most of these transcriptional changes. CONCLUSION: The pathogenesis of Blau
      syndrome may be mediated by IL-1, and canakinumab may be useful when this
      disorder is unresponsive to more conventional treatments.

PMID- 23124806
TI  - Hyperpolarized helium-3 magnetic resonance imaging of chronic obstructive
      pulmonary disease exacerbation.
AB  - A chronic obstructive pulmonary disease (COPD) exsmoker underwent pulmonary
      function tests and hyperpolarized helium-3 ((3) He) magnetic resonance imaging
      (MRI) serially over 4 years, twice prior to and twice following an acute
      exacerbation (AE). About 2.5 years pre-AE, (3) He ventilation defect percent
      (VDP) was 16%, the apparent diffusion coefficient (ADC) was 0.34 cm(2) /s, and
      forced expiratory volume in 1 sec (FEV1 ) was 41%pred . Six months pre-AE, VDP
      and ADC were worse (29% and 0.38 cm(2) /s, respectively) without worsening FEV1
      (47%pred ). After hospitalization and AE treatment, VDP was 20%, whereas FEV1 did
      not improve (45%pred ); 16 months post-AE, both VDP and ADC remained improved and
      similar to 4 years prior.

PMID- 23124807
TI  - Charcot's arthropathy of the spine.

PMID- 23124808
TI  - Specializations of intercellular junctions are associated with the presence and
      absence of hair cell regeneration in ears from six vertebrate classes.
AB  - Sensory hair cell losses lead to hearing and balance deficits that are permanent
      for mammals, but temporary for nonmammals because supporting cells in their ears
      give rise to replacement hair cells. In mice and humans, vestibular supporting
      cells grow exceptionally large circumferential F-actin belts and their junctions
      express E-cadherin in patterns that strongly correlate with postnatal declines in
      regeneration capacity. In contrast, chicken supporting cells retain thin F-actin
      belts throughout life and express little E-cadherin. To determine whether the
      junctions in chicken ears might be representative of other ears that also
      regenerate hair cells, we investigated inner ears from dogfish sharks, zebrafish,
      bullfrogs, Xenopus, turtles, and the lizard, Anolis. As in chickens, the
      supporting cells in adult zebrafish, Xenopus, and turtle ears retained thin
      circumferential F-actin belts and expressed little E-cadherin. Supporting cells
      in adult sharks and bullfrogs also retained thin belts, but were not tested for E
      cadherin. Supporting cells in adult Anolis exhibited wide, but porous webs of F
      actin and strong E-cadherin expression. Anolis supporting cells also showed some
      cell cycle reentry when cultured. The results reveal that the association between
      thin F-actin belts and low E-cadherin is shared by supporting cells in
      anamniotes, turtles, and birds, which all can regenerate hair cells. Divergent
      junctional specializations in supporting cells appear to have arisen
      independently in Anolis and mammals. The presence of webs of F-actin at the
      junctions in Anolis appears compatible with supporting cell proliferation, but
      the solid reinforcement of the F-actin belts in mammals is associated with its
      absence.

PMID- 23124811
TI  - Subsyndromal delirium in older people: a systematic review of frequency, risk
      factors, course and outcomes.
AB  - OBJECTIVE: To determine the frequency, risk factors, course and outcomes of
      subsyndromal delirium (SSD) in older people by systematically reviewing evidence
      on these topics. METHODS: Subsyndromal delirium was defined as the presence of
      one or more symptoms of delirium, not meeting criteria for delirium and not
      progressing to delirium. MEDLINE, EMBASE, PsycINFO and the Web of Science were
      searched for potentially relevant articles published from 1996 to June 2011. The
      bibliographies of relevant articles were searched for additional references.
      Twelve studies met the inclusion criteria. The validity of included studies was
      assessed according to Evidence-Based Medicine criteria. Information about the
      study population and methods, age, gender, proportion with dementia, diagnostic
      criteria, period and frequency of observation, and the topics above was
      systematically abstracted, tabulated and synthesized using standard meta-analysis
      techniques. RESULTS: The combined prevalence of SSD was 23% (95% CI, 9-42%); the
      combined incidence was 13% (95% CI, 6-23%). Risk factors were similar to those
      for delirium. Episodes lasted up to 133 days and were often recurrent. Outcomes
      were poor and often intermediate between those of older people with or without
      delirium. Of note, there was significant unexplained heterogeneity in the results
      of studies of prevalence, incidence and some risk factors. CONCLUSIONS: SSD in
      older people may be a frequent and clinically important condition that falls on a
      continuum between no symptoms and full delirium. Because of significant
      unexplained heterogeneity in the results of studies of SSD, however, the results
      of this review must be interpreted cautiously. Further research is necessary.

PMID- 23124809
TI  - PLD4 as a novel susceptibility gene for systemic sclerosis in a Japanese
      population.
AB  - OBJECTIVE: Systemic sclerosis (SSc) is an autoimmune disease for which multiple
      susceptibility genes have been reported. Genome-wide association studies have
      shown that large numbers of susceptibility genes are shared among autoimmune
      diseases. Recently, our group identified 9 novel susceptibility genes associated
      with rheumatoid arthritis (RA) in a Japanese population. The aim of this study
      was to elucidate whether the 18 genes that displayed associations or suggestive
      associations for RA in our previous study are associated with SSc in Japanese.
      METHODS: We performed an association study that included 415 patients with SSc
      and 16,891 control subjects, followed by a replication study that included 315
      patients and 21,054 control subjects. The 18 markers reported to display
      association with RA were analyzed for their associations with SSc in the first
      study, and 5 markers were further analyzed in the replication study. The inverse
      variance method was used to evaluate the associations of these markers with SSc
      in a combined study. RESULTS: In the phospholipase D4 gene (PLD4), rs2841277
      displayed a significant association with SSc in Japanese patients (P = 0.00017).
      We observed that rs2841280 in exon 2 of PLD4 was in strong linkage disequilibrium
      with rs2841277 and introduced an amino acid alteration. We also observed
      associations between SSc and rs6932056 in TNFAIP3 and rs2280381 in IRF8 (P =
      0.0000095 and P = 0.0030, respectively), both of which displayed associations
      with SSc in a European population. CONCLUSION: We determined that PLD4 is a novel
      susceptibility gene for SSc in Japanese, thus confirming the involvement of PLD4
      in autoimmunity. Associations between SSc and TNFAIP3 or IRF8 were also detected
      in our Japanese population. SSc and RA appear to share relatively large
      proportions of their genetic backgrounds.

PMID- 23124812
TI  - A novel synthetic peptide from a tomato defensin exhibits antibacterial
      activities against Helicobacter pylori.
AB  - Defensins are a class of cysteine-rich proteins, which exert broad spectrum
      antimicrobial activity. In this work, we used a bioinformatic approach to
      identify putative defensins in the tomato genome. Fifteen proteins had a mature
      peptide that includes the well-conserved tetradisulfide array. We selected a
      representative member of the tomato defensin family; we chemically synthesized
      its gamma-motif and tested its antimicrobial activity. Here, we demonstrate that
      the synthetic peptide exhibits potent antibacterial activity against Gram
      positive bacteria, such as Staphylococcus aureus A170, Staphylococcus
      epidermidis, and Listeria monocytogenes, and Gram-negative bacteria, including
      Salmonella enterica serovar Paratyphi, Escherichia coli, and Helicobacter pylori.
      In addition, the synthetic peptide shows minimal (<5%) hemolytic activity and
      absence of cytotoxic effects against THP-1 cells. Finally, SolyC exerts an anti
      inflammatory activity in vitro, as it downregulates the level of the
      proinflammatory cytokines TNF-alpha and IFN-gamma.

PMID- 23124813
TI  - Off-line determination of the optimal number of iterations of the robust
      anisotropic diffusion filter applied to denoising of brain MR images.
AB  - Although anisotropic diffusion filters have been used extensively and with great
      success in medical image denoising, one limitation of this iterative approach,
      when used on fully automatic medical image processing schemes, is that the
      quality of the resulting denoised image is highly dependent on the number of
      iterations of the algorithm. Using many iterations may excessively blur the edges
      of the anatomical structures, while a few may not be enough to remove the
      undesirable noise. In this work, a mathematical model is proposed to
      automatically determine the number of iterations of the robust anisotropic
      diffusion filter applied to the problem of denoising three common human brain
      magnetic resonance (MR) images (T1-weighted, T2-weighted and proton density). The
      model is determined off-line by means of the maximization of the mean structural
      similarity index, which is used in this work as metric for quantitative
      assessment of the resulting processed images obtained after each iteration of the
      algorithm. After determining the model parameters, the optimal number of
      iterations of the algorithm is easily determined without requiring any extra
      computation time. The proposed method was tested on 3D synthetic and clinical
      human brain MR images and the results of qualitative and quantitative evaluation
      have shown its effectiveness.

PMID- 23124810
TI  - Cognitive mapping in humans and its relationship to other orientation skills.
AB  - Human orientation in novel and familiar environments is a complex skill that can
      involve numerous different strategies. To date, a comprehensive account of how
      these strategies interrelate at the behavioural level has not been documented,
      impeding the development of elaborate systems neuroscience models of spatial
      orientation. Here, we describe a virtual environment test battery designed to
      assess five of the core strategies used by humans to orient. Our results indicate
      that the ability to form a cognitive map is highly related to more basic
      orientation strategies, supporting previous proposals that encoding a cognitive
      map requires inputs from multiple domains of spatial processing. These findings
      provide a topology of numerous primary orientation strategies used by humans
      during orientation and will allow researchers to elaborate on neural models of
      spatial cognition that currently do not account for how different orientation
      strategies integrate over time based on environmental conditions.

PMID- 23124814
TI  - Biomechanical analysis of the wrist arthroplasty in rheumatoid arthritis: a
      finite element analysis.
AB  - The total replacement of wrists affected by rheumatoid arthritis (RA) has had
      mixed outcomes in terms of failure rates. This study was therefore conducted to
      analyse the biomechanics of wrist arthroplasty using recently reported implants
      that have shown encouraging results with the aim of providing some insights for
      the future development of wrist implants. A model of a healthy wrist was
      developed using computed tomography images from a healthy volunteer. An RA model
      was simulated based on all ten general characteristics of the disease. The
      ReMotion TM total wrist system was then modelled to simulate total wrist
      arthroplasty (TWA). Finite element analysis was performed with loads simulating
      the static hand grip action. The results show that the RA model produced
      distorted patterns of stress distribution with tenfold higher contact pressure
      than the healthy model. For the TWA model, contact pressure was found to be
      approximately fivefold lower than the RA model. Compared to the healthy model,
      significant improvements were observed for the TWA model with minor variations in
      the stress distribution. In conclusion, the modelled TWA reduced contact pressure
      between bones but did not restore the stress distribution to the normal healthy
      condition.

PMID- 23124815
TI  - Practical limits on muscle synergy identification by non-negative matrix
      factorization in systems with mechanical constraints.
AB  - Statistical decomposition, including non-negative matrix factorization (NMF), is
      a convenient tool for identifying patterns of structured variability within
      behavioral motor programs, but it is unclear how the resolved factors relate to
      actual neural structures. Factors can be extracted from a uniformly sampled, low
      dimension command space. In practical application, the command space is limited,
      either to those activations that perform some task(s) successfully or to
      activations induced in response to specific perturbations. NMF was applied to
      muscle activation patterns synthesized from low dimensional, synergy-like control
      modules mimicking simple task performance or feedback activation from
      proprioceptive signals. In the task-constrained paradigm, the accuracy of control
      module recovery was highly dependent on the sampled volume of control space, such
      that sampling even 50% of control space produced a substantial degradation in
      factor accuracy. In the feedback paradigm, NMF was not capable of extracting more
      than four control modules, even in a mechanical model with seven internal degrees
      of freedom. Reduced access to the low-dimensional control space imposed by
      physical constraints may result in substantial distortion of an existing low
      dimensional controller, such that neither the dimensionality nor the composition
      of the recovered/extracted factors match the original controller.

PMID- 23124816
TI  - Standard error of inverse prediction for dose-response relationship: approximate
      and exact statistical inference.
AB  - This paper develops a new metric, the standard error of inverse prediction
      (SEIP), for a dose-response relationship (calibration curve) when dose is
      estimated from response via inverse regression. SEIP can be viewed as a
      generalization of the coefficient of variation to regression problem when x is
      predicted using y-value. We employ nonstandard statistical methods to treat the
      inverse prediction, which has an infinite mean and variance due to the presence
      of a normally distributed variable in the denominator. We develop confidence
      intervals and hypothesis testing for SEIP on the basis of the normal
      approximation and using the exact statistical inference based on the noncentral t
      distribution. We derive the power functions for both approaches and test them via
      statistical simulations. The theoretical SEIP, as the ratio of the regression
      standard error to the slope, is viewed as reciprocal of the signal-to-noise
      ratio, a popular measure of signal processing. The SEIP, as a figure of merit for
      inverse prediction, can be used for comparison of calibration curves with
      different dependent variables and slopes. We illustrate our theory with electron
      paramagnetic resonance tooth dosimetry for a rapid estimation of the radiation
      dose received in the event of nuclear terrorism.

PMID- 23124818
TI  - Comorbid ADHD and mental health disorders: are these children more likely to
      develop reading disorders?
AB  - While attention-deficit/hyperactivity disorder (ADHD) has been associated with
      both internalizing and externalizing childhood behaviour disorders, the specific
      relationship of these comorbid disorders to ADHD and reading problems is less
      well defined. The present study analysed data from the Australian Twin ADHD
      Project, which utilized DSM-IV-based ratings of ADHD, separation anxiety
      disorder, generalized anxiety disorder, depression, conduct disorder, and
      oppositional defiant disorder for twins and siblings aged 6 to 18 years. While
      differences between children with and without ADHD were demonstrated for those
      with separation anxiety disorder, generalized anxiety disorder, depression,
      conduct disorder, oppositional defiant disorder and a reading disorder, for all
      age groups, regression analysis of ADHD diagnostic subtypes by age and reading
      disorder showed that only generalized anxiety disorder remained significant after
      controlling for ADHD subtypes. Analysis of the mean reading disorder scores in
      children with and without ADHD showed that children with conduct disorder had
      significantly more reading problems, as did children with multiple comorbid
      disorders. In summary, both age and ADHD diagnosis were associated with
      variations in these comorbid disorders, and multiple comorbid disorders were
      associated with greater reading impairment.

PMID- 23124817
TI  - Health status and health insurance coverage of women with live-born infants: an
      opportunity for preventive services after pregnancy.
AB  - Most women in the US have access to health care and insurance during pregnancy;
      however women with Medicaid-paid deliveries lose Medicaid eligibility in the
      early postpartum period. This study examined the association between health
      insurance coverage at the time of delivery and health conditions that may require
      preventive or treatment services extending beyond pregnancy into the postpartum
      period. We used 2008 Pregnancy Risk Assessment Monitoring System data from 27
      states (n = 35,980). We calculated the prevalence of maternal health conditions,
      including emotional and behavioral risks, by health insurance status at the time
      of delivery. We used multivariable logistic regression to assess the association
      between health insurance coverage, whether Medicaid or private, and maternal
      health status. As compared to women with private health insurance, women with
      Medicaid-paid deliveries had higher odds of reporting smoking during pregnancy
      (adjusted odds ratio [AOR]: 1.85, 95 % confidence interval [CI]: 1.56-2.18),
      physical abuse during pregnancy (AOR: 1.73, 95 % CI: 1.24-2.40), having six or
      more stressors during pregnancy (AOR: 2.48, 95 % CI: 1.93-3.18), and experiencing
      postpartum depressive symptoms (AOR: 1.24, 95 % CI: 1.04-1.48). There were no
      significant differences by insurance status at delivery in pre-pregnancy
      overweight/obesity, pre-pregnancy physical activity, weight gain during
      pregnancy, alcohol consumption during pregnancy, or postpartum contraceptive use.
      Compared to women with private insurance, women with Medicaid-paid deliveries
      were more likely to experience risk factors during pregnancy such as physical
      abuse, stress, and smoking, and postpartum depressive symptoms for which
      continued screening, counseling, or treatment in the postpartum period could be
      beneficial.

PMID- 23124819
TI  - Dissolution of platinum: limits for the deployment of electrochemical energy
      conversion?
AB  - Platinum stability: Dissolution of Pt, which is one major degradation mechanism
      in, for example, hydrogen/air fuel cells, was monitored under potentiodynamic and
      potentiostatic conditions. The highly sensitive and time-resolving dissolution
      monitoring enables the distinction between anodic and cathodic dissolution
      processes during potential transient and chronoamperometric experiments, and the
      precise quantification of the amount of dissolved Pt.

PMID- 23124820
TI  - Cholesterol and Alzheimer's disease: a still poorly understood correlation.
AB  - A large amount of evidence suggests a pathogenic link between cholesterol
      homeostasis dysregulation and Alzheimer's disease (AD). In cell culture systems,
      the production of amyloid-beta (Abeta) is modulated by cholesterol, and studies
      on animal models have consistently demonstrated that hypercholesterolemia is
      associated with an increased deposition of cerebral Abeta peptides. Consequently,
      a number of epidemiological studies have examined the effects of cholesterol
      lowering drugs (i.e., statins) in the prevention and the treatment of AD.
      However, while retrospective studies suggested a potential benefit of statin
      therapy, clinical trials produced inconsistent results. Here, we summarize the
      main findings from in vitro and in vivo research where the correlation between
      cholesterol and the neurodegenerative disorder was investigated. Recognition of
      this correlation could be an important step forward for our understanding of AD
      pathogenesis and, possibly, for the development of new therapeutic strategies.

PMID- 23124821
TI  - Fluid shift from intravascular compartment during fetal red blood cell
      transfusion.
AB  - OBJECTIVES: Intrauterine transfusion imposes a considerable burden on the fetal
      circulation by increasing volume and pressure, and a fluid shift from the fetal
      circulation occurs even during the procedure. The aim of this study was to
      quantify the intraprocedural fluid shift and to investigate the effect of
      procedural and fetal characteristics on this fluid shift. METHODS: In 95
      alloimmunized pregnancies, we calculated fluid shift at the first intrauterine
      transfusion by determining initial and final blood volumes. We evaluated the
      association of the fluid shift with the speed and volume of the transfusion, the
      severity of anemia and the presence of hydrops. RESULTS: Of the included fetuses,
      11 were mildly hydropic and four were severely hydropic. A mean fluid shift of
      36% of the transfused volume was found. Fluid shift related positively to
      transfused volume (P < 0.001). The percentage fluid shift of transfused volume
      was inversely related to the speed of transfusion (mL/kg/min) (P < 0.041) and was
      not related to the severity of anemia (P = 0.55) or to hydrops (P = 0.66). It was
      found that younger fetuses had been unintentionally subject to high volumes and
      speeds of transfusion relative to their size. CONCLUSIONS: Around one-third of
      the transfused volume is lost from the intravascular compartment during the
      procedure of intrauterine transfusion. There is a large variation between
      fetuses, partly explained by the volume and speed of the transfusion. Neither
      severity of anemia nor hydrops plays a clear-cut role, and thus other factors may
      explain the variation in fluid shift. The probability that hematocrit will still
      increase after transfusion, as a result of a continuing fluid shift, should be
      considered in transfusion policy. Advice is given on gestational age-adjusted
      speed of transfusion.

PMID- 23124823
TI  - Tandem Heck/decarboxylation/Heck strategy: protecting-group-free synthesis of
      symmetric and unsymmetric hydroxylated stilbenoids.

PMID- 23124822
TI  - Association of legumain expression pattern with prostate cancer invasiveness and
      aggressiveness.
AB  - OBJECTIVES: To investigate the clinical implication of legumain, an asparaginyl
      endopeptidase that is highly expressed in several types of cancer, expression in
      prostate cancer. METHODS: Legumain expression in prostate cancer cell lines was
      determined by real-time reverse transcriptase PCR and Western blot. Furthermore,
      legumain expression in 88 prostatectomy specimens was evaluated by
      immunohistochemistry. The association between legumain expression and
      clinicopathological factors was analyzed. RESULTS: Legumain expression was
      confirmed at the mRNA and protein levels in all the cells. Although all the
      cancer tissues were positive for legumain, 2 staining patterns were observed in
      the cytoplasm: diffuse cytoplasmic and vesicular positivity. The rates of Gleason
      score >=8, extracapsular extension, and perineural invasion in the group with
      vesicular staining were significantly higher than those in the diffuse
      cytoplasmic group (p < 0.05). The maximum size of the tumor with vesicular
      staining was significantly greater than that of the tumor with diffuse
      cytoplasmic staining (p = 0.0302). The 5-year biochemical recurrence-free rate in
      the patients with vesicular legumain staining was 53.2%; this rate was
      significantly lower than that (78.8%) in the patients with diffuse cytoplasmic
      staining (p = 0.0269). CONCLUSIONS: Tumors that showed a vesicular staining
      pattern of legumain had the potential of being highly invasive and aggressive in
      patients with prostate cancer who were treated with radical prostatectomy. This
      suggests that legumain might contribute to the invasiveness and aggressiveness of
      prostate cancer.

PMID- 23124824
TI  - Relationship Stability through Lenses of Complexity.
AB  - Research on relationship stability usually considers the effect of couple
      outcomes and individual differences on relationship stability in isolation from
      each other. These separate bodies of research often lead to inconsistent results.
      In order to better understand relationship stability and explain inconsistencies
      in the literature, it is important to investigate more complex models that
      integrate couple outcomes and behaviors with individual differences. Motivated by
      these considerations, we examined the complex interplay between personal
      characteristics, couple interactions, and relationship stability. In particular,
      we investigated the relationships among investment model, big five personality
      traits, attachment dimensions, relationship factors and relationship stability.
      Participants of this study included 162 individuals (Female N=117) who are
      currently in a relationship from a large Midwestern university campus. Analyses
      were conducted using Structural Equation Modeling. Examination of the structural
      path parameters indicated that attachment had significant direct effect on
      personality, relationship factors, and relationship stability. Personality also
      had a significant direct effect on relationship stability. Finally personality
      had no direct effect on relationship factors and relationship factors had no
      direct effect on relationship stability. These results suggest that the effect of
      personality on relationship stability is direct, rather than being mediated by
      relationship factors.

PMID- 23124825
TI  - Sonographic diagnosis of a viable abdominal pregnancy with planned delivery after
      fetal lung maturation.
AB  - We report a case of a viable abdominal pregnancy with successful outpatient
      management until fetal lung maturation and planned delivery. Advanced abdominal
      pregnancy is a very rare extrauterine pregnancy, which results in serious
      maternal and fetal morbidity. A 28-year-old nullipara was referred from the local
      clinic to our tertiary center at 18 weeks' gestation. We diagnosed an
      extrauterine fetus on sonographic examination. The patient had weekly antenatal
      sonographic examinations. We performed a planned laparotomy at 34 weeks'
      gestation, and a female baby weighing 2,100 g was delivered. The placenta was
      completely removed and the uterus was preserved. Both the mother and the baby had
      no postoperative morbidity.

PMID- 23124826
TI  - Independent analysis of the radiation risk for leukaemia in children and adults
      with mortality data (1950-2003) of Japanese A-bomb survivors.
AB  - A recent analysis of leukaemia mortality in Japanese A-bomb survivors has applied
      descriptive models, collected together from previous studies, to derive a joint
      excess relative risk estimate (ERR) by multi-model inference (MMI) (Walsh and
      Kaiser in Radiat Environ Biophys 50:21-35, 2011). The models use a linear
      quadratic dose response with differing dose effect modifiers. In the present
      study, a set of more than 40 models has been submitted to a rigorous statistical
      selection procedure which fosters the parsimonious deployment of model parameters
      based on pairwise likelihood ratio tests. Nested models were consequently
      excluded from risk assessment. The set comprises models of the excess absolute
      risk (EAR) and two types of non-standard ERR models with sigmoidal responses or
      two line spline functions with a changing slope at a break point. Due to clearly
      higher values of the Akaike Information Criterion, none of the EAR models has
      been selected, but two non-standard ERR models qualified for MMI. The preferred
      ERR model applies a purely quadratic dose response which is slightly damped by an
      exponential factor at high doses and modified by a power function for attained
      age. Compared to the previous analysis, the present study reports similar point
      estimates and confidence intervals (CI) of the ERR from MMI for doses between 0.5
      and 2.5 Sv. However, at lower doses, the point estimates are markedly reduced by
      factors between two and five, although the reduction was not statistically
      significant. The 2.5 % percentiles of the ERR from the preferred quadratic
      exponential model did not fall below zero risk in exposure scenarios for
      children, adolescents and adults at very low doses down to 10 mSv. Yet, MMI
      produced risk estimates with a positive 2.5 % percentile only above doses of some
      300 mSv. Compared to CI from a single model of choice, CI from MMI are broadened
      in cohort strata with low statistical power by a combination of risk
      extrapolations from several models. Reverting to MMI can relieve the dilemma of
      needing to choose between models with largely different consequences for risk
      assessment in public health.

PMID- 23124827
TI  - Chronic low-dose exposure in the Techa River Cohort: risk of mortality from
      circulatory diseases.
AB  - The aim of the present study was to analyze the mortality from circulatory
      diseases for about 30,000 members of the Techa River cohort over the period 1950
      2003, and to investigate how these rates depend on radiation doses. This
      population received both external and internal exposures from (90)Sr, (89)Sr,
      (137)Cs, and other uranium fission products as a result of waterborne releases
      from the Mayak nuclear facility in the Southern Urals region of the Russian
      Federation. The analysis included individualized estimates of the total (external
      plus internal) absorbed dose in muscle calculated based on the Techa River
      Dosimetry System 2009. The cohort-average dose to muscle tissue was 35 mGy, and
      the maximum dose was 510 mGy. Between 1950 and 2003, 7,595 deaths from
      circulatory diseases were registered among cohort members with 901,563 person
      years at risk. Mortality rates in the cohort were analyzed using a simple
      parametric excess relative risk (ERR) model. For all circulatory diseases, the
      estimated excess relative risk per 100 mGy with a 15-year lag period was 3.6 %
      with a 95 % confidence interval of 0.2-7.5 %, and for ischemic heart disease it
      was 5.6 % with a 95 % confidence interval of 0.1-11.9 %. A linear ERR model
      provided the best fit. Analyses with a lag period shorter than 15 years from the
      beginning of exposure did not reveal any significant risk of mortality from
      either all circulatory diseases or ischemic heart disease. There was no evidence
      of an increased mortality risk from cerebrovascular disease (p > 0.5). These
      results should be regarded as preliminary, since they will be updated after
      adjustment for smoking and alcohol consumption.

PMID- 23124828
TI  - Sirtuin 1 enzymatic activity is required for cartilage homeostasis in vivo in a
      mouse model.
AB  - OBJECTIVE: We and others previously demonstrated that sirtuin 1 (SIRT-1)
      regulates apoptosis and cartilage-specific gene expression in human chondrocytes
      and mouse models. This study was undertaken to determine if SIRT-1 enzymatic
      activity plays a protective role in cartilage homeostasis in vivo, by
      investigating mice with SIRT-1 mutations to characterize their cartilage.
      METHODS: Articular cartilage was harvested from the paws and knees of 5- and 6
      month-old wild-type (WT) mice and mice homozygous for SIRT-1tm2.1Mcby (SIRT
      1y/y), an allele carrying a point mutation that encodes a SIRT-1 protein with no
      enzymatic activity (y/y mice). Mice ages 2 days old and 6-7 days old were also
      examined. Mouse joint cartilage was processed for histologic examination or
      biochemical analyses of chondrocyte cultures. RESULTS: We found that articular
      cartilage tissue sections from y/y mice of up to 6 months of age contained
      reduced levels of type II collagen, aggrecan, and glycosaminoglycan compared to
      sections from WT mice. In contrast, protein levels of matrix metalloproteinase 8
      (MMP-8), MMP-9, and MMP-13 were elevated in the cartilage of y/y mice. In
      addition, chondrocyte apoptosis was elevated in SIRT-1 mutant mice as compared to
      their WT littermates. Consistent with these observations, protein tyrosine
      phosphatase 1b was elevated in the y/y mice. CONCLUSION: Our in vivo findings in
      this animal model demonstrate that mice with defective SIRT-1 also have defective
      cartilage, with elevated rates of cartilage degradation with age. Hence, normal
      cartilage homeostasis requires enzymatically active SIRT-1 protein.

PMID- 23124830
TI  - The distinct pathogenesis of IgG4 Mickulicz's disease and Sjogren's syndrome in
      Japan; the role of IL-21 and IL-6.

PMID- 23124829
TI  - Comparison of polycyclic aromatic hydrocarbon emissions on gasoline- and diesel
      dominated routes.
AB  - Three diesel-dominated routes (DDRs) and three gasoline-dominated routes (GDRs)
      were chosen as the study sites. The total number of vehicles on GDRs (47,200) was
      much higher than that on DDRs (14,500). The concentration of polycyclic aromatic
      hydrocarbons (PAHs), elemental carbon, organic carbon, and metals from GDR
      roadsides was higher than that for DDRs. The diagnostic ratios (ANTHR/PHE +
      ANTHR, FLT/FLT + PYR, BaA/BaA + CHR, and IND/IND + BghiP + ANTHN) all indicated
      that the major PAH source on DDR and GDR was emissions from vehicle engine
      combustion. The marked diesel ratios of low molecular weight PAH2.5/T-PAH2.5,
      methyl-PAH2.5/T-PAH2.5, methyl-PHE/PHE, and Mo/PM2.5 on DDRs were higher than
      those on GDRs. Significant correlations were found between the number of vehicles
      and the concentration of T-PAH2.5, Car-PAHs2.5, and BaPeq2.5 on DDRs and GDRs.
      The increase in the levels of T-PAH2.5, Car-PAHs2.5, and BaPeq2.5 per 100
      vehicles on DDRs was about 3.3, 3.5, and 4.2 times higher than that on GDRs,
      respectively. The higher percentage of high-exhaust volume from the larger amount
      of diesel vehicles on DDRs than that on GDRs was the main factor leading to these
      results. The diagnostic ratios BaA2.5/CHR2.5 and (BbF + BkF)2.5/BghiP2.5 showed
      significant differences between the fine PAH sources emitted on DDRs and GDRs,
      whereas the diagnostic ratios Me-PAH2.5/T-PAH2.5 and (BbF + BkF)2.5/BghiP2.5
      showed good correlations with the percentages of diesel exhaust volume in the
      total exhaust volume (E(diesel)/E(total)) on DDRs.

PMID- 23124831
TI  - Exploring moral distress in potential sibling stem cell donors.
AB  - In relation to the phenomenon of moral distress, this article presents two
      original perspectives. First, the literature to date reflects a focus on moral
      distress in an occupational context. In this article, however, the impact of
      moral distress on siblings is explored. Moral distress is considered in a
      particular context, stem cell donation, but there are clear insights and
      implications for wider practice, particularly in life-threatening contexts and
      situations where live donation enhances the potential for survival. Second, the
      article represents some progress in relation to creating conceptual clarity. It
      is suggested that in addition to external and internal moral constraints a
      further classification of constraint emerges, and that this is useful in teasing
      out the distinction between moral stress and moral distress. The insights drawn
      from exploring the experiences of these siblings should enhance the ability to
      pre-empt and ameliorate potential distress and, ultimately, reduce harm.

PMID- 23124832
TI  - Mapping owl's eye cells of patients with cytomegalovirus corneal endotheliitis
      using in vivo laser confocal microscopy.
AB  - PURPOSE: To produce a two-dimensional reconstruction map of owl's eye cells using
      in vivo laser confocal microscopy in patients with cytomegalovirus (CMV) corneal
      endotheliitis, and to demonstrate any association between owl's eye cells and
      coin-shaped lesions observed with slit-lamp biomicroscopy. METHOD: Two patients
      (75- and 77-year-old men) with polymerase chain reaction-proven CMV corneal
      endotheliitis were evaluated in this study. Slit-lamp biomicroscopy and in vivo
      laser confocal microscopy were performed. Images of owl's eye cells in the
      endothelial cell layer were arranged and mapped into subconfluent montages.
      Montage images of owl's eye cells were then superimposed on a slit-lamp photo of
      the corresponding coin-shaped lesion. Degree of concordance between the confocal
      microscopic images and slit-lamp photos was evaluated. RESULTS: In both eyes, a
      two-dimensional reconstruction map of the owl's eye cells was created by computer
      software using acquired confocal images; the maps showed circular patterns.
      Superimposing montage images of owl's eye cells onto the photos of a coin-shaped
      lesion showed good concordance in the two eyes. CONCLUSIONS: This study suggests
      that there is an association between owl's eye cells observed by confocal
      microscopy and coin-shaped lesions observed by slit-lamp biomicroscopy in
      patients with CMV corneal endotheliitis. The use of in vivo laser confocal
      microscopy may provide clues as to the underlying causes of CMV corneal
      endotheliitis.

PMID- 23124833
TI  - Corneal biomechanical properties in eyes with no previous surgery, with previous
      penetrating keratoplasty and with deep anterior lamellar keratoplasty.
AB  - PURPOSE: To compare the biomechanical properties of the cornea in eyes with no
      previous surgery, with keratoconus with previous penetrating keratoplasty (PK)
      and with keratoconus with previous deep anterior lamellar keratoplasty (DALK)
      using the Reichert Ocular Response Analyzer (ORA). METHODS: One hundred twenty
      eyes of 120 patients were included in this prospective comparative study. Forty
      eyes were with no previous ocular surgery (group 1), 40 eyes were with previous
      PK for keratoconus (group 2), and 40 eyes were with previous DALK for keratoconus
      (group 3). Corneal hysteresis (CH) and the corneal resistance factor (CRF) were
      measured with ORA. RESULTS: The CH and CRF values in group 2 were significantly
      lower than in group 1 and group 3 (p = 0.001). The CH and CRF values were similar
      in group 1 and group 3. There was no statistically significant difference between
      group 1 and 3. CONCLUSION: Although the post-PK keratoconus cornea has weaker
      biomechanical properties, post-DALK keratoconus cornea is similar to normal
      cornea. A cornea weakened by keratoconus can be strengthened with lamellar
      keratoplasty.

PMID- 23124834
TI  - Use of 3T MRI and an unspoiled 3D fast gradient echo sequence for porcine knee
      cartilage volumetry: preliminary findings.
AB  - PURPOSE: To assess the utility of knee cartilage volumetry using an unspoiled fat
      suppressed 3D fast gradient echo (FGRE) sequence at 3T. MATERIALS AND METHODS:
      Sagittal magnetic resonance (MR) images were obtained with an unspoiled fat
      suppressed 3D FGRE sequence in eight porcine knees. Manual segmentation was used
      to derive the cartilage volume. This volume was compared to a volume measurement
      of cartilage scraping specimens obtained by water displacement. Imaging was
      repeated five times in four of the knees to assess interscan volume measurement
      reproducibility and calculate precision error. A single 3D dataset was manually
      segmented five times at weekly intervals to assess intraobserver volume
      measurement reproducibility. RESULTS: Total cartilage volume obtained from MRI
      and water displacement correlated well (r = 0.75). The interscan reproducibility
      of total volume measurements, expressed as the coefficient of variation (CV), was
      4.2%, and the precision error (root mean square [RMS] CV) was 4.1%. The CV of
      intraobserver estimates of total cartilage volume by MRI was 3.6%. CONCLUSION:
      Interscan reproducibility of quantification of total cartilage volume and
      reproducibility of the manual segmentation technique were both high (>95%).
      Accurate and reproducible cartilage volumetry can be obtained by using a clinical
      unspoiled fat-suppressed 3D FGRE acquired at 3T MRI.

PMID- 23124835
TI  - Differential recruitment and activation of natural killer cell sub-populations by
      Mycobacterium bovis-infected dendritic cells.
AB  - Through complex interplay with APCs, subsets of NK cells play an important role
      in shaping adaptive immune responses. Bovine tuberculosis, caused by
      Mycobacterium bovis, is increasing in incidence and detailed knowledge of host
      pathogen interactions in the natural host is essential to facilitate disease
      control. We investigated the interactions of NK-cell sub-populations and M. bovis
      infected DCs to determine early innate mechanisms in the response to infection. A
      sub-population of NK cells (NKp46(+) CD2(-) ) selectively expressing lymphoid
      homing and inflammatory chemokine receptors were induced to migrate towards M.
      bovis-infected DCs. This migration was associated with increased expression of
      chemokines CCL3, 4, 5, 20 and CXCL8 by M. bovis-infected DCs. Activation of
      NKp46(+) CD2(-)  NK cells and secretion of IFN-gamma was observed, a response
      reliant on localised IL-12 release and direct cellular interaction. In a
      reciprocal manner, NKp46(+) CD2(-)  cells induced an increase in the intensity of
      cell surface MHC class II expression on DCs. In contrast, NKp46(+) CD2(+)  NK
      cells were unable to secrete IFN-gamma and did not reciprocally affect DCs. This
      study provides novel evidence to demonstrate distinct effector responses between
      bovine NK-cell subsets during mycobacterial infection.

PMID- 23124836
TI  - Functional, anatomical, and neurochemical differentiation of medial preoptic area
      subregions in relation to maternal behavior in the mouse.
AB  - In rodents, previous findings indicate critical involvement of the medial
      preoptic area (MPOA) in the neural control of maternal behavior. However, the
      specification of the particular MPOA subregions involved in maternal behavior and
      the identification of the neurochemical phenotype(s) of the essential neurons
      demands additional study. Therefore, we investigated the chemical neuroanatomy of
      the essential MPOA subregion for maternal behavior in C57BL/6J female mice. Using
      the oxytocinergic neurons in the dorsal MPOA as a primary regional marker, we
      first assessed the distribution of c-Fos-expressing neurons in the MPOA during
      maternal behavior using immunohistochemistry. Results showed that non
      oxytocinergic neurons in the dorsal and ventral MPOA prominently expressed c-Fos
      during maternal behavior. Then using excitotoxic lesion studies, we determined
      the specific MPOA area that is necessary for maternal behavior. Bilateral lesions
      of the central MPOA, where c-Fos was expressed only moderately, effectively
      disrupted maternal behavior, although lesions to the dorsal and ventral MPOA
      regions were ineffective. These centrally lesioned females were highly
      infanticidal irrespective of their previous maternal experience. Neurochemical
      investigations showed that more than 75% of the c-Fos-expressing neurons in
      central MPOA were GABAergic. Many of them also expressed galanin, neurotensin,
      and/or tachykinin2 mRNAs. Finally, the central MPOA was populated by numerous
      glutamatergic neurons, although only a small percentage of these neurons
      colocalized with c-Fos. To conclude, the central MPOA is the indispensable
      subregion for mouse maternal behavior, and GABAergic and/or peptidergic neurons
      in this area were transcriptionally activated during maternal behavior.

PMID- 23124839
TI  - The time constant of the somatogravic illusion.
AB  - Without visual feedback, humans perceive tilt when experiencing a sustained
      linear acceleration. This tilt illusion is commonly referred to as the
      somatogravic illusion. Although the physiological basis of the illusion seems to
      be well understood, the dynamic behavior is still subject to discussion. In this
      study, the dynamic behavior of the illusion was measured experimentally for three
      motion profiles with different frequency content. Subjects were exposed to pure
      centripetal accelerations in the lateral direction and were asked to indicate
      their tilt percept by means of a joystick. Variable-radius centrifugation during
      constant angular rotation was used to generate these motion profiles. Two self
      motion perception models were fitted to the experimental data and were used to
      obtain the time constant of the somatogravic illusion. Results showed that the
      time constant of the somatogravic illusion was on the order of two seconds, in
      contrast to the higher time constant found in fixed-radius centrifugation
      studies. Furthermore, the time constant was significantly affected by the
      frequency content of the motion profiles. Motion profiles with higher frequency
      content revealed shorter time constants which cannot be explained by self-motion
      perception models that assume a fixed time constant. Therefore, these models need
      to be improved with a mechanism that deals with this variable time constant.
      Apart from the fundamental importance, these results also have practical
      consequences for the simulation of sustained accelerations in motion simulators.

PMID- 23124840
TI  - p27(Kip1)  inhibits systemic autoimmunity through the control of Treg cell
      activity and differentiation.
AB  - OBJECTIVE: Despite the importance of Treg cells in the maintenance of immunologic
      tolerance, the mechanisms that control their generation and activity are unknown.
      Since the cell cycle inhibitor p27(Kip1)  (p27) was involved in T cell anergy, we
      undertook this study to explore its role in both Treg cell processes. METHODS:
      The development of type II collagen-induced arthritis (CIA) and lupus-like
      abnormalities was compared between transgenic mice overexpressing human Bcl-2 in
      T cells (BCL2-TgT mice) and nontransgenic mice that were deficient or not
      deficient in p27. The contribution of Treg cells to disease evolution was also
      explored. Finally, the in vitro activity of Treg cells and their differentiation
      from naive CD4+ cells was compared between these strains of mice. RESULTS: BCL2
      TgT mice were protected against CIA by a Treg cell-dependent mechanism. In
      association with this protection, the overexpression of Bcl-2 in T cells enhanced
      the differentiation and activity of Treg cells. Both Bcl-2 effects were
      independent of its antiapoptotic activity but dependent on its capacity to induce
      the expression of p27 that augmented the strength of transforming growth factor
      beta (TGFbeta) signaling in T cells. Accordingly, down-modulation of p27
      expression in BCL2-TgT mice promoted CIA. In addition, p27 deficiency in aged
      C57BL/6 mice reduced the number and activity of Treg cells and induced the
      development of mild lupus-like abnormalities. CONCLUSION: Our results point to
      p27 as a critical regulator of Treg cell differentiation and function through the
      positive modulation of TGFbeta signaling strength in T cells.

PMID- 23124837
TI  - mTOR-dependent cell survival mechanisms.
AB  - The mechanistic target of rapamycin (mTOR) kinase is a conserved regulator of
      cell growth, proliferation, and survival. In cells, mTOR is the catalytic subunit
      of two complexes called mTORC1 and mTORC2, which have distinct upstream
      regulatory signals and downstream substrates. mTORC1 directly senses cellular
      nutrient availability while indirectly sensing circulating nutrients through
      growth factor signaling pathways. Cellular stresses that restrict growth also
      impinge on mTORC1 activity. mTORC2 is less well understood and appears only to
      sense growth factors. As an integrator of diverse growth regulatory signals, mTOR
      evolved to be a central signaling hub for controlling cellular metabolism and
      energy homoeostasis, and defects in mTOR signaling are important in the
      pathologies of cancer, diabetes, and aging. Here we discuss mechanisms by which
      each mTOR complex might regulate cell survival in response to metabolic and other
      stresses.

PMID- 23124842
TI  - Can brucellosis influence the course of chronic hepatitis C in dual infection?
AB  - Hepatitis C and brucellosis are infectious diseases that occur worldwide, and
      both are endemic in Egypt. Co-infection with both agents is possible, and this
      can involve the liver in various ways. In this study, we investigated serum
      tissue inhibitor metalloproteinase-1 (TIMP-1), viral load, and liver functions in
      patients co-infected with hepatitis C virus (HCV) before and after brucellosis
      treatment. Over 3 years, 241 consecutive HCV patients (before interferon therapy
      was received) with recurrent fever who had occupational contact with animals were
      tested for brucellosis co-infection by a standard tube agglutination test. In
      patients with dual infection, viraemia (RT-PCR), TIMP-1 measured by ELISA, and
      liver functions were assessed and re-evaluated 2 months after brucellosis
      treatment. The number of patients with HCV/brucellosis co-infection was 32 out of
      241 (13.3%). TIMP-1, viraemia, AST, ALT and bilirubin showed significant decrease
      (improvement) after brucellosis treatment (p < 0.001) but an insignificant
      difference (p > 0.05) with regard to serum albumin and prothrombin concentration.
      The study revealed that brucellosis is an important infection in HCV-infected
      patients and can aggravate the course of disease, suggesting that early treatment
      and prevention are important.

PMID- 23124841
TI  - Psychopathology in the aftermath of the Haiti earthquake: a population-based
      study of posttraumatic stress disorder and major depression.
AB  - BACKGROUND: In the first population-based study of psychopathology conducted in
      Haiti, we documented earthquake-related experiences associated with risk for
      posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) 2-4
      months following the 2010 Haiti earthquake. METHODS: A population-based survey
      was conducted of 1,323 survivors randomly selected from the general nondisplaced
      community, internally displaced persons camps, and a community clinic.
      Respondents were from the Nazon area of Port-au-Prince, ~20 miles from the
      epicenter. RESULTS: Respondents (90.5%) reported at least one relative/close
      friend injured/killed, 93% saw dead bodies, and 20.9% lost their job post
      earthquake. The prevalence of PTSD (24.6%) and MDD (28.3%) was high. History of
      violent trauma was associated with risk of PTSD and MDD (adjusted odds ratio
      [AOR] 1.4, 95% confidence interval [CI], 1.0-1.9; AOR, 1.7, 95% CI 1.3, 2.2,
      respectively). Low social support (AOR, 1.7, 95% CI 1.2, 2.3; AOR 1.4, 95% CI
      1.0, 1.9, respectively) increased risk of PTSD and MDD among women. Suffering
      damage to the home increased risk of MDD in males (AOR 2.8, 95% CI 1.5, 5.5).
      Associations between being trapped in rubble, major damage to house, job loss,
      and PTSD; and participation in rescue/recovery, friends/family injured/killed,
      and MDD varied based on prior history of violent trauma. CONCLUSIONS: Addressing
      mental health in a post-earthquake setting such as Haiti will require focusing
      resources on screening and treatment of identified vulnerable groups while
      targeting improvement of post-earthquake living conditions. Investment in sources
      of social support for women may make help mitigate the vulnerability of women to
      PTSD and MDD.

PMID- 23124845
TI  - A highly efficient photocatalyst--hydrogenated black TiO2 for the photocatalytic
      splitting of water.
AB  - In black and white: The hydrogenation of TiO(2) can extend its optical absorption
      into the visible and infrared region and change its color from white to black.
      Furthermore, the hydrogenated black TiO(2) exhibits excellent photocatalytic
      activity for the splitting of water to yield H(2).

PMID- 23124843
TI  - Genetic diversity of porcine sapoviruses, kobuviruses, and astroviruses in
      asymptomatic pigs: an emerging new sapovirus GIII genotype.
AB  - Small, non-enveloped RNA viruses belonging to the genera Sapovirus, Kobuvirus,
      and Mamastrovirus are usually associated with gastroenteritis in humans and
      animals. These enteric pathogens are considered potential zoonotic agents. In
      this study, the prevalence and genetic diversity of sapoviruses (SaVs),
      kobuviruses (KoVs), and astroviruses (AstVs) in asymptomatic pigs were
      investigated using a PCR approach. KoV was found to be the most prevalent virus
      (87.3 %), followed by AstV (34.2 %) and SaV (10.2 %). Interestingly, the intra-
      and inter-cluster distances between porcine SaV capsid sequences revealed one
      strain (P38/11/CZ) that formed a new genotype within genogroup III of porcine
      SaVs, and it is tentatively called "P38/11-like" genotype. Moreover, this is the
      first report of porcine kobuvirus detection on Czech pig farms. The high
      prevalence rate of gastroenteritis-producing viruses in clinically healthy pigs
      represents a continuous source of infection of pigs, and possibly to humans.

PMID- 23124844
TI  - Functional connectivity networks associated with chronic musculoskeletal pain in
      old age.
AB  - OBJECTIVE: Musculoskeletal disorders are common and often lead to chronic pain in
      older adults. Because the efficacy of interventions varies with the duration of
      pain, the identification of early biomarkers for chronic pain would have
      important public health consequences. Imaging of functional connectivity
      differences between brain regions might identify some of the earliest functional
      consequences of a disease process. We tested the hypothesis that chronic
      musculoskeletal pain in older persons is associated with changes in functional
      brain connectivity. METHOD: We used resting-state functional magnetic resonance
      imaging and a spherical seed-based region of interest approach to assess
      functional connectivity of brain regions on a sample of 128 (64 who reported
      chronic musculoskeletal pain and 64 demographically matched, pain free)
      nondemented older adults from the Memory and Aging Project, a clinical
      pathological cohort study of aging and dementia. RESULTS: Older adults with
      chronic pain showed greater functional connectivity between the posterior
      cingulate and left insula, left superior temporal gyrus, and left cerebellum.
      CONCLUSION: Chronic musculoskeletal pain is associated with a specific pattern of
      functional connectivity between brain regions among older adults.

PMID- 23124846
TI  - Nitrogen-doped graphene foams as metal-free counter electrodes in high
      performance dye-sensitized solar cells.

PMID- 23124847
TI  - Accurate risk assessment of patients with asymptomatic hematuria for the presence
      of bladder cancer.
AB  - PURPOSE: Bladder cancer is frequently diagnosed during a workup for hematuria.
      However, most patients with microscopic hematuria and many with gross hematuria
      are not appropriately referred to urologists. We hypothesized that in patients
      presenting with asymptomatic hematuria the risk of having bladder cancer can be
      predicted with high accuracy. Toward this end, we analyzed risk factors in
      patients with asymptomatic hematuria and developed a nomogram for the prediction
      of bladder cancer presence. METHODS: Data from 1,182 consecutive subjects without
      a history of bladder cancer undergoing initial evaluation for asymptomatic
      hematuria were collected at three centers. Clinical risk factors including age,
      gender, smoking status, and degree of hematuria were recorded. All subjects
      underwent standard workup including voided cytology, upper tract imaging, and
      cystourethroscopy. Factors associated with the presence of bladder cancer were
      evaluated by univariable and multivariable logistic regression analyses. The
      multivariable analysis was used to construct a nomogram. Internal validation was
      performed using 200 bootstrap samples. RESULTS: Of the 1,182 subjects who
      presented with asymptomatic hematuria, 245 (20.7 %) had bladder cancer.
      Increasing age (OR = 1.03, p < 0.0001), smoking history (OR = 3.72, p < 0.0001),
      gross hematuria (OR = 1.71, p = 0.002), and positive cytology (OR = 14.71, p <
      0.0001) were independent predictors of bladder cancer presence. The multivariable
      model achieved 83.1 % accuracy for predicting the presence of bladder cancer.
      CONCLUSIONS: Bladder cancer presence can be predicted with high accuracy in
      patients who present with asymptomatic hematuria. We developed a nomogram to help
      optimize referral patterns (i.e., timing and prioritization) of patients with
      asymptomatic hematuria.

PMID- 23124849
TI  - An exploratory study of the interplay between decreased concentration of
      tryptophan, accumulation of kynurenines, and inflammatory arthritis.
AB  - Tryptophan is an essential amino acid which influences a wide range of
      physiological processes, including mood, cognition, and immunity. In the
      autoimmune diseases, such as rheumatoid arthritis (RA), the induction of
      tryptophan catabolism may help to diminish exacerbated immune responses. In this
      study, using collagen-induced arthritis (CIA) in DBA/1 mice which is an animal
      model of RA, the endogenous activity of the kynurenine pathway in the immune
      system was monitored before and after onset of the disease. An increased rate of
      the initiation of tryptophan catabolism via the kynurenine pathway throughout CIA
      has been observed. However, decreased tryptophan concentration in the lymph nodes
      from pre-arthritic mice was not enough to prevent development of CIA. In
      contrast, resolution of inflammation coincided with the decreased concentration
      of tryptophan and accumulation of its catabolites: kynurenine, anthranilic acid,
      and 3-hydroxyanthranilic acid in lymph nodes but not in the spleen. In addition,
      the lack of the accumulation of kynurenine and its downstream metabolites in the
      pre-arthritic lymph nodes coincided with increased mRNA expression for genes
      involved in the catabolism of kynurenine (Kynureninase, kynurenine 3
      monooxygenase, and 3-hydroxyanthranilate 3,4 dioxygenase). However, in the lymph
      nodes from mice with established CIA, mRNA expression for these genes was
      normalized. Hence, keeping in mind an exploratory character of the results, it
      can be postulated that an anti-inflammatory role of the kynurenine pathway
      reaches its full potential only when decreased concentration of tryptophan
      coincides with accumulation of kynurenines driven by metabolic regulation of gene
      expression on the kynurenine pathway.

PMID- 23124848
TI  - Brief Report: Single-nucleotide polymorphisms in VKORC1 are risk factors for
      systemic lupus erythematosus in Asians.
AB  - OBJECTIVE: The increased risk of thrombosis in systemic lupus erythematosus (SLE)
      may be partially explained by interrelated genetic pathways for thrombosis and
      SLE. The present study was undertaken to investigate whether 33 established and
      novel single-nucleotide polymorphisms (SNPs) in 20 genes involved in hemostasis
      pathways that have been associated with deep venous thrombosis (DVT) in the
      general population are risk factors for SLE among Asian subjects. METHODS:
      Patients in the discovery cohort were enrolled in 1 of 2 North American SLE
      cohorts. Patients in the replication cohort were enrolled in 1 of 4 Asian or 2
      North American cohorts. We first genotyped 263 Asian patients with SLE and 357
      healthy Asian control subjects for 33 SNPs in the discovery phase, and then
      genotyped 5 SNPs in up to an additional 1,496 patients and 993 controls in the
      replication phase. Patients were compared to controls for bivariate association
      with minor alleles. Principal components analysis was used to control for intra
      Asian ancestry in the replication cohort. RESULTS: Two genetic variants in the
      gene VKORC1 were highly significant in both the discovery and replication
      cohorts: rs9934438 (in the discovery cohort, odds ratio [OR] 2.45, P=2*10(-9); in
      the replication cohort, OR 1.54, P=4*10(-6)) and rs9923231 (in the discovery
      cohort, OR 2.40, P=6*10(-9); in the replication cohort, OR 1.53, P=5*10(-6)).
      These associations were significant in the replication cohort after adjustment
      for intra-Asian ancestry: for rs9934438, OR 1.34, P=0.0029; for rs9923231, OR
      1.34, P=0.0032. CONCLUSION: Genetic variants in VKORC1, which are involved in
      vitamin K reduction and associated with DVT, correlate with SLE development in
      Asian subjects. These results suggest that there may be intersecting genetic
      pathways for the development of SLE and thrombosis.

PMID- 23124850
TI  - Nowcasting influenza epidemics using non-homogeneous hidden Markov models.
AB  - Timeliness of a public health surveillance system is one of its most important
      characteristics. The process of predicting the present situation using available
      incomplete information from surveillance systems has received the term nowcasting
      and has high public health interest. Generally in Europe, general practitioners'
      sentinel networks support the epidemiological surveillance of influenza activity,
      and each week's epidemiological bulletins are usually issued between Wednesday
      and Friday of the following week. In this work, we have developed a non
      homogeneous hidden Markov model (HMM) that, on a weekly basis, uses as covariates
      an early observation of influenza-like illness (ILI) incidence rate and the
      number of ILI cases tested positive to nowcast the current week ILI rate and the
      probability that the influenza activity is in an epidemic state. We use Bayesian
      inference to find estimates of the model parameters and nowcasted quantities. The
      results obtained with data provided by the Portuguese influenza surveillance
      system show the additional value of using a non-homogeneous HMM instead of a
      homogeneous one. The use of a non-homogeneous HMM improves the surveillance
      system timeliness in 2 weeks.

PMID- 23124851
TI  - Chronic treatment with LY294002, an inhibitor of phosphatidylinositol 3-kinase,
      attenuates ischemia/reperfusion-induced cardiac dysfunction in normotensive and
      hypertensive diabetic animals.
AB  - Diabetes is associated with increased incidence of cardiovascular disease.
      Mechanisms that contribute to development of diabetic cardiopathy are not well
      understood. Phosphatidylinositol 3-kinase (PI3K) is a family of protein kinases
      that play an important role in regulation of cardiac function. It has been shown
      that inhibition of certain PI3K enzymes may produce cardiovascular protection.
      The aim of the present study was to determine whether chronic treatment with
      LY294002, an inhibitor of PI3K, can attenuate diabetes-induced cardiac
      dysfunction in isolated hearts obtained from normotensive and hypertensive rats.
      Recovery of cardiac function after 40 min of global ischemia and 30 min of
      reperfusion, measured as left ventricular developed pressure, left ventricular
      end-diastolic pressure, coronary flow and coronary vascular resistance, was worse
      in hearts obtained from diabetic and/or hypertensive animals compared to their
      respective controls. Treatment with LY294002 (1.2 mg/kg/day) for 4 weeks
      significantly prevented diabetes-induced cardiac dysfunction in both normotensive
      and hypertensive rats. Treatment with LY294002 did not significantly alter blood
      pressure or blood glucose levels. These results suggest that inhibition of PI3K
      signaling pathways can prevent ischemia/reperfusion-induced cardiac dysfunction
      in normotensive and hypertensive rats without correcting hyperglycemia or high
      blood pressure.

PMID- 23124852
TI  - Wnt/beta-catenin signaling induces the aging of mesenchymal stem cells through
      promoting the ROS production.
AB  - Recent studies have demonstrated that the Wnt/beta-catenin signaling plays an
      important role in stem cell aging. However, the mechanisms of cell senescence
      induced by Wnt/beta-catenin signaling are still poorly understood. Our
      preliminary study has indicated that activated Wnt/beta-catenin signaling can
      induce MSC aging. In this study, we reported that the Wnt/beta-catenin signaling
      was a potent activator of reactive oxygen species (ROS) generation in MSCs. After
      scavenging ROS with N-acetylcysteine, Wnt/beta-catenin signaling-induced MSC
      aging was significantly attenuated and the DNA damage and the expression of
      p16(INK4A), p53, and p21 were reduced in MSCs. These results indicated that the
      Wnt/beta-catenin signaling could induce MSC aging through promoting the
      intracellular production of ROS, and ROS may be the main mediators of MSC aging
      induced by excessive activation of Wnt/beta-catenin signaling.

PMID- 23124853
TI  - Biochemical markers of vascular calcification in elderly hemodialysis patients.
AB  - The increased vascular calcification, cardiovascular morbidity, and mortality in
      chronic kidney disease (CKD) patients has been associated with disturbances in
      mineral-bone metabolism. In order to determine markers of the vascular
      calcification frequently observed in these patients, blood samples of elderly
      male and female hemodialysis CKD patients were used to measure serum levels of:
      osteoprotegerin (OPG), total soluble receptor activator of nuclear factor-kappaB
      ligand (sRANKL), and fetuin-A by enzyme immunoassay; tartrate-resistant acid
      phosphatase (TRACP-5b), and bone-specific alkaline phosphatase (BAP) by
      immunoenzymometric assay; osteocalcin (OC) by ELISA; iPTH by immunoradiometric
      assay; 25(OH)D(3) and 1,25(OH)(2)D(3), by I(125) radioimmunoassay; and calcium
      and phosphorus by photometric assay. Serum OPG, BAP, iPTH, phosphorus, and OC
      levels were higher and serum 25(OH)D(3), 1,25(OH)(2)D(3), and fetuin-A levels
      lower in both male and female CKD patients than in their respective controls. Our
      results indicate that the bone formation and resorption parameters are altered in
      elderly male and female hemodialysis CKD patients. These changes may lead to
      vascular calcifications and cardiovascular complications, given that elevated OPG
      and OC levels and reduced fetuin-A levels are associated with cardiovascular
      events.

PMID- 23124855
TI  - Gender differences in diagnostic testing for suspected coronary artery disease?

PMID- 23124854
TI  - Activation of the unfolded protein response during anoxia exposure in the turtle
      Trachemys scripta elegans.
AB  - Red-eared slider turtles, Trachemys scripta elegans, can survive for several
      weeks without oxygen when submerged in cold water. We hypothesized that
      anaerobiosis is aided by adaptive up-regulation of the unfolded protein response
      (UPR), a stress-responsive pathway that is activated by accumulation of unfolded
      proteins in the endoplasmic reticulum (ER) and functions to restore ER
      homeostasis. RT-PCR, western immunoblotting and DNA-binding assays were used to
      quantify the responses and/or activation status of UPR-responsive genes and
      proteins in turtle tissues after animal exposure to 5 or 20 h of anoxic
      submergence at 4  degrees C. The phosphorylation state of protein kinase-like ER
      kinase (PERK) (a UPR-regulated kinase) and eukaryotic initiation factor 2
      (eIF2alpha) increased by 1.43-2.50 fold in response to anoxia in turtle heart,
      kidney, and liver. Activation of the PERK-regulated transcription factor,
      activating transcription factor 4 (ATF4), during anoxia was documented by
      elevated atf4 transcripts and total ATF4 protein (1.60-2.43 fold), increased
      nuclear ATF4 content, and increased DNA-binding activity (1.44-2.32 fold). ATF3
      and GADD34 (downstream targets of ATF4) also increased by 1.38-3.32 fold in heart
      and liver under anoxia, and atf3 transcripts were also elevated in heart. Two
      characteristic chaperones of the UPR, GRP78, and GRP94, also responded positively
      to anoxia with strong increases in both the transcript and protein levels. The
      data demonstrate that the UPR is activated in turtle heart, kidney, and liver in
      response to anoxia, suggesting that this pathway mediates an integrated stress
      response to protect tissues during oxygen deprivation.

PMID- 23124856
TI  - Symptomatic severe aortic stenosis in the TAVI era: heart team assessment for
      all.

PMID- 23124859
TI  - microRNAs: fine tuning of erythropoiesis.
AB  - Cell proliferation and differentiation is a complex process involving many
      cellular mechanisms. One of the best-studied phenomena in cell differentiation is
      erythrocyte development during hematopoiesis in vertebrates. In recent years, a
      new class of small, endogenous, non-coding RNAs called microRNAs (miRNAs) emerged
      as important regulators of gene expression at the post-transcriptional level.
      Thousands of miRNAs have been identified in various organisms, including
      protozoa, fungi, bacteria and viruses, proving that the regulatory miRNA pathway
      is conserved in evolution. There are many examples of miRNA-mediated regulation
      of gene expression in the processes of cell proliferation, differentiation and
      apoptosis, and in cancer genesis. Many of the collected data clearly show the
      dependence of the proteome of a cell on the qualitative and quantitative
      composition of endogenous miRNAs. Numerous specific miRNAs are present in the
      hematopoietic erythroid line. This review attempts to summarize the state of
      knowledge on the role of miRNAs in the regulation of different stages of
      erythropoiesis. Original experimental data and results obtained with
      bioinformatics tools were combined to elucidate the currently known regulatory
      network of miRNAs that guide the process of differentiation of red blood cells.

PMID- 23124857
TI  - Liprin alpha3: a putative estrogen regulated acrosomal protein.
AB  - Liprin alpha3 was reported for the first time using sperm proteomics. Present
      study reports its localization on sperm and immunochemical characterization.
      Liprin alpha3 is identified as a 133 kDa protein in testis and epididymal protein
      extracts. In testis, immunohistochemical localization was seen in pachytenes,
      diplotenes, round spermatids whereas it was localized in the epithelial cells and
      luminal sperm in all the three regions of epididymis. Protein was localized in
      acrosome of rat sperm, which was further confirmed by sequential treatment of
      sperm with hypertonic solution. In the spermatogenic cells the protein was found
      to be located in developing acrosome as evident by its co-localization with Golgi
      marker. Protein was found to be developmentally regulated. In silico analysis of
      Liprin alpha3 revealed presence of the estrogen responsive elements upstream to
      initiation site and its regulation by estrogen was experimentally validated using
      a tamoxifen treated rat model. Western blot analysis of epididymosomes showed the
      presence of Liprin alpha3, indicating its involvement in trafficking of vesicle.
      The protein expression was seen in both mouse and human sperm indicating
      conserved nature and a probable role in acrosome reaction.

PMID- 23124858
TI  - Regulation of angiogenesis by hypoxia: the role of microRNA.
AB  - Understanding the cellular pathways that regulate angiogenesis during hypoxia is
      a necessary aspect in the development of novel treatments for cardiovascular
      disorders. Although the pathways of angiogenesis have been extensively studied,
      there is limited information on the role of miRNAs in this process. miRNAs or
      their antagomirs could be used in future therapeutic approaches to regulate
      hypoxia-induced angiogenesis, so it is critical to understand their role in
      governing angiogenesis during hypoxic conditions. Although hypoxia and ischemia
      change the expression profile of many miRNAs, a functional role for a limited
      number of so-called hypoxamiRs has been demonstrated in angiogenesis. Here, we
      discuss the best examples that illustrate the role of hypoxamiRs in angiogenesis.

PMID- 23124860
TI  - Practice patterns for the management of hepatic metastases from colorectal
      cancer: a mixed methods analysis.
AB  - PURPOSE: The optimal management of colorectal cancer liver metastases (CRC-LM)
      has changed during the past two decades. However, clinical practice lags behind
      best evidence recommendations. We sought to characterize the gap between current
      practice and best evidence for the management of these patients and to identify
      barriers that hamper effective utilization of metastasectomy. METHODS: A mixed
      methods approach was used. A survey was mailed to all general surgeons (GS) and
      medical oncologists (MO) in Ontario, Canada. Domains examined included:
      physician/practice characteristics, indications for hepatectomy, use of multi
      modality therapy and referral patterns. Physician focus groups were conducted
      that explored issues relating to access to care. RESULTS: The survey was mailed
      to 942 physicians with a response rate of 68 % (n = 348; GS n = 295, 69 %; MO n =
      53, 63 %). Current practice patterns demonstrated that 97 % of physicians refer
      patients with low tumor burden (e.g., solitary CRC-LM), but referral rates for
      hepatectomy decreased as the tumor burden increased. Physicians still consider
      extrahepatic disease as a strong contraindication to metastasectomy. Barriers to
      care included: economic, time, and resource constraints; lack of physician
      engagement, local medical expertise, and high-quality guidelines.
      Multidisciplinary cancer conferences were identified as an enabler of clinical
      care and a potential platform for the acquisition of new medical knowledge.
      CONCLUSIONS: Current management of CRC-LM does not reflect best evidence.
      Patients who may benefit from surgery are not being referred for metastasectomy.
      We have identified an evidence-practice gap at the level of physician, which
      should be targeted with novel quality improvement strategies.

PMID- 23124862
TI  - From specific to global analysis of posttranscriptional regulation in eukaryotes:
      posttranscriptional regulatory networks.
AB  - Regulation of gene expression occurs at several levels in eukaryotic organisms
      and is a highly controlled process. Although RNAs have been traditionally viewed
      as passive molecules in the pathway from transcription to translation, there is
      mounting evidence that their metabolism is controlled by a class of proteins
      called RNA-binding proteins (RBPs), as well as a number of small RNAs. In this
      review, I provide an overview of the recent developments in our understanding of
      the repertoire of RBPs across diverse model systems, and discuss the
      computational and experimental approaches currently available for the
      construction of posttranscriptional networks governed by them. I also present an
      overview of the different roles played by RBPs in the cellular context, based on
      their cis-regulatory modules identified in the literature and discuss how their
      interplay can result in the dynamic, spatial and tissue-specific expression maps
      of RNAs. I finally present the concept of posttranscriptional network of RBPs and
      their cognate RNA targets and discuss their cross-talk with other important
      posttranscriptional regulatory molecules such as microRNAs s, resulting in
      diverse functional network motifs. I argue that with rapid developments in the
      genome-wide elucidation of posttranscriptional networks it would not only be
      possible to gain a deeper understanding of regulation at a level that has been
      under-appreciated in the past, but would also allow us to use the newly developed
      high-throughput approaches to interrogate the prevalence of these phenomena in
      different states, and thereby study their relevance to physiology and disease
      across organisms.

PMID- 23124863
TI  - Codon 72 polymorphism of p53 and HPV type 16 E6 variants as risk factors for
      patients with squamous epithelial lesion of the uterine cervix.
AB  - The Arg/Arg genotype versus Arg/Pro or Pro/Pro at codon 72 of the p53 gene in
      association with human papillomavirus (HPV) 16 E6 variants has been implicated as
      a risk marker in cervical neoplasia. However, research on this topic has produced
      controversial results. The association of p53 codon 72 polymorphism alone and in
      combination with specific HPV 16 E6 variants with risk of developing squamous
      intraepithelial cervical lesion has been investigated in low and high-grade
      squamous intraepithelial lesions and in HPV-negative controls from an Italian
      population. The data obtained showed statistically significant different
      distribution of p53 genotypes between healthy controls and precursor lesions,
      with the p53 arginine homozygous increased in high-grade squamous intraepithelial
      lesions. The T350G HPV 16 variant was the most frequent variant observed in the
      analyzed group of Italian women, showing a slight decreasing with the severity of
      the lesion. At the same time, the number of the prototype T350 slightly increased
      with the severity of the cytological lesions. In conclusion, p53 arginine
      homozygous was found to be increased in high-grade lesions, supporting the
      results of previous investigations indicating that HPV-positive patients with p53
      Arg/Arg have an increased risk of developing pre-cancerous lesions. In addition,
      T350G HPV 16 variant was over-represented in p53 Arg homozygous women with
      cervical lesions. When p53 genotype and HPV 16 variants are considered together,
      no difference emerges between cases and controls so is not possible to assess
      that the oncogenic effect of HPV 16 T350G variant may be influenced by the p53
      genotype.

PMID- 23124864
TI  - A questionnaire to document self-medication history in adult patients visiting
      emergency departments.
AB  - PURPOSE: To develop the first questionnaire to obtain a complete medication
      history by documenting self-medication history in adult patients admitted to a
      medical emergency department (ED). METHODS: A Questionnaire to document Self
      Medicating Behaviours (QSMB) was developed between January and September 2008
      (reference period), tested and refined between October and December 2008, and
      used routinely between January and December 2009 (routine period) in a tertiary
      care medical ED. The rate of SMBs measured with QSMB during the routine period
      was compared to the SMB rate measured with a spontaneous reporting method during
      the reference period. As survey teams changed every trimester, we also analysed
      the evolution of SMB rate over time. RESULTS: QSMB is divided into two parts. The
      first part consists of 20 closed-ended questions exploring all indications and
      dimensions of self-medication. The second part assesses the characteristics of
      each medication mentioned by the patient in the first 20 questions. The patients
      interviewed during reference and routine periods did not significantly differ.
      The routine period patients reported a third more SMBs (89.8% vs 57.6%,
      respectively; p < 0.0001) and twice more self-medication drugs than the reference
      period patients. SMB rate was significantly different between the survey teams
      during the reference period (p < 0.0001), but not during the routine period (p =
      0.078). CONCLUSIONS: This questionnaire complements the traditional tools that
      are already available to collect medication histories of prescribed drugs. It may
      improve the recognition of iatrogenic conditions related to self-medication, and
      provide support to public health efforts and research programs on self
      medication.

PMID- 23124865
TI  - Reevaluation of a walleye (Sander vitreus) bioenergetics model.
AB  - Walleye (Sander vitreus) is an important sport fish throughout much of North
      America, and walleye populations support valuable commercial fisheries in certain
      lakes as well. Using a corrected algorithm for balancing the energy budget, we
      reevaluated the performance of the Wisconsin bioenergetics model for walleye in
      the laboratory. Walleyes were fed rainbow smelt (Osmerus mordax) in four
      laboratory tanks each day during a 126-day experiment. Feeding rates ranged from
      1.4 to 1.7% of walleye body weight per day. Based on a statistical comparison of
      bioenergetics model predictions of monthly consumption with observed monthly
      consumption, we concluded that the bioenergetics model estimated food consumption
      by walleye without any significant bias. Similarly, based on a statistical
      comparison of bioenergetics model predictions of weight at the end of the monthly
      test period with observed weight, we concluded that the bioenergetics model
      predicted walleye growth without any detectable bias. In addition, the
      bioenergetics model predictions of cumulative consumption over the 126-day
      experiment differed from observed cumulative consumption by less than 10%.
      Although additional laboratory and field testing will be needed to fully evaluate
      model performance, based on our laboratory results, the Wisconsin bioenergetics
      model for walleye appears to be providing unbiased predictions of food
      consumption.

PMID- 23124866
TI  - Muscle development and body growth in larvae and early post-larvae of shi drum,
      Umbrina cirrosa L., reared under different larval photoperiod: muscle structural
      and ultrastructural study.
AB  - Shi drum specimens were maintained under four different photoperiod regimes: a
      natural photoperiod regime (16L:8D), constant light (24L), equal durations of
      light and dark (12L:12D) and a reduced number of daylight hours (6L:18D) from
      hatching until the end of larval metamorphosis. Specimens were then kept under
      natural photoperiod conditions until 111 days post-hatching. Muscle and body
      parameters were studied. During the vitelline phase, there was little muscle
      growth and no photoperiod effects were reported; however, a monolayer of red
      muscle and immature white muscle fibres were observed in the myotome. At
      hatching, external cells (presumptive myogenic cells) were already present on the
      surface of the red muscle. At the mouth opening, some presumptive myogenic cells
      appeared between the red and white muscles. At 20 days, new germinal areas were
      observed in the apical extremes of the myotome. At this stage, the 16L:8D group
      (followed by the 24L group) had the longest body length, the largest cross
      sectional area of white muscle and the largest white muscle fibres. Conversely,
      white muscle hyperplasia was most pronounced in the 24L group. Metamorphosis was
      complete at 33 days in the 24L and 12L:12D groups. At this moment, both groups
      showed numerous myogenic precursors on the surface of the myotome as well as
      among the adult muscle fibres (mosaic hyperplastic growth). The 16L:8D group
      completed metamorphosis at 50 days, showing a similar degree of structural
      maturity in the myotome to that described in the 24L and 12L:12D groups at 33
      days. When comparing muscle growth at the end of the larval period, hypertrophy
      was highest in the 16L:8D group, whereas hyperplasia was higher in the 24L and
      16L:8D groups. At 111 days, all groups showed the adult muscle pattern typical of
      teleosts; however, the cross-sectional area of white muscle, white muscle fibre
      hyperplasia, body length and body weight were highest in the 24L group, followed
      by the 12L:12D group; white muscle hypertrophy was similar in all groups. Larval
      survival was higher under natural photoperiod conditions compared to all the
      other light regimes.

PMID- 23124868
TI  - From the angio suite to the gamma-camera: vascular mapping and 99mTc-MAA hepatic
      perfusion imaging before liver radioembolization--a comprehensive pictorial
      review.
AB  - Endovascular mapping and conjoint (99m)Tc-macroaggregated albumin ((99m)Tc-MAA)
      hepatic perfusion imaging provide essential information before liver
      radioembolization with (90)Y-loaded microspheres in patients with primary and
      secondary hepatic malignancies. The aims of this integrated procedure are to
      determine whether there is a risk for excessive shunting of (90)Y-microspheres to
      the lungs; to detect extrahepatic perfusion emerging from the injected vascular
      territory, which might lead to nontargeted radioembolization; to reveal
      incomplete coverage of the liver parenchyma involved by the tumor, which may be
      related to anatomic or acquired variants of the arterial vasculature; and to aid
      in calculation of the (90)Y-microsphere dose to be delivered to the liver. This
      pictorial essay presents an integrated comprehensive review of the anatomic,
      angiographic, and nuclear imaging aspects of planned liver radioembolization. The
      relevant anatomy of the liver, including the standard and the variant arterial
      vasculature, will be shown using digital subtraction angiography, SPECT/CT,
      contrast-enhanced CT, and anatomic illustrations. Technical details that will
      optimize the imaging protocols and important imaging findings will be discussed.
      From the angio suite to the gamma-camera-the goal of this review is to help the
      reader better understand how the technical details of the angiographic procedure
      are reflected in the imaging findings of the (99m)Tc-MAA hepatic perfusion study.
      In addition, the reader should learn to better recognize the pertinent findings
      and their clinical implications. This knowledge will enable the reader to provide
      a more useful interpretation of this complex multidisciplinary procedure.

PMID- 23124869
TI  - Henry N. Wagner, Jr., MD 1927-2012.

PMID- 23124871
TI  - Berman receives de Hevesy Award.

PMID- 23124867
TI  - Projections of the superior colliculus to the pulvinar in prosimian galagos
      (Otolemur garnettii) and VGLUT2 staining of the visual pulvinar.
AB  - An understanding of the organization of the pulvinar complex in prosimian
      primates has been somewhat elusive due to the lack of clear architectonic
      divisions. In the current study we reveal features of the organization of the
      pulvinar complex in galagos by examining superior colliculus (SC) projections to
      this structure and comparing them with staining patterns of the vesicular
      glutamate transporter, VGLUT2. Cholera toxin subunit beta (CTB), Fluoro-ruby
      (FR), and wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP)
      were placed in topographically different locations within the SC. Our results
      showed multiple topographically organized patterns of projections from the SC to
      several divisions of the pulvinar complex. At least two topographically
      distributed projections were found within the lateral region of the pulvinar
      complex, and two less obvious topographical projection patterns were found within
      the caudomedial region, in zones that stain darkly for VGLUT2. The results,
      considered in relation to recent observations in tree shrews and squirrels,
      suggest that parts of the organizational scheme of the pulvinar complex in
      primates are present in rodents and other mammals.

PMID- 23124872
TI  - Alavi and Larson awarded 2012 Benedict Cassen Prize.

PMID- 23124873
TI  - Humm recognized with Loevinger-Berman Award.

PMID- 23124874
TI  - Goodman recognized with 2012 Aebersold Award.

PMID- 23124875
TI  - Robert E. Henkin Government Relations Fellowship.

PMID- 23124876
TI  - A bright future on the horizon for SNMMI.

PMID- 23124877
TI  - Flt3 ligand expands CD4+ FoxP3+ regulatory T cells in human subjects.
AB  - CD4(+) CD25(+) FoxP3(+)  naturally occurring regulatory T (Treg) cells play a
      crucial role in the maintenance of immune tolerance and in preventing autoimmune
      pathology. Interventions that expand Treg cells are highly desirable, as they may
      offer novel treatment options in a variety of autoimmune and transplantation
      settings. Paralleling previous preclinical studies, we demonstrate here that
      administration of the hematopoietic growth factor Flt3L to human subjects
      increases the frequency and absolute number of Treg cells, and reduces the ratio
      of CD8(+)  T cells to Treg cells in the peripheral blood. The increase in Treg
      cells was due to enhanced Treg-cell proliferation rather than release of Treg
      cells from the thymus. Further studies revealed that Flt3L-induced proliferation
      of Treg cells was an indirect effect that occurred via the interaction of Treg
      cells with the Flt3L-expanded pool of CD1c(+)  myeloid dendritic cells. On the
      basis of these findings, Flt3L may represent a promising agent for promoting
      immune tolerance in a variety of clinical settings.

PMID- 23124879
TI  - Oligothiophene amphiphiles as planarizable and polarizable fluorescent membrane
      probes.

PMID- 23124878
TI  - beta-catenin regulates parathyroid hormone/parathyroid hormone-related protein
      receptor signals and chondrocyte hypertrophy through binding to the intracellular
      C-terminal region of the receptor.
AB  - OBJECTIVE: To investigate the underlying mechanisms of action and functional
      relevance of beta-catenin in chondrocytes, by examining the role of beta-catenin
      as a novel protein that interacts with the intracellular C-terminal portion of
      the parathyroid hormone (PTH)/PTH-related protein (PTHrP) receptor type 1 (PTHR
      1). METHODS: The beta-catenin-PTHR-1 binding region was determined with deletion
      and mutagenesis analyses of the PTHR1 C-terminus, using a mammalian two-hybrid
      assay. Physical interactions between these 2 molecules were examined with an in
      situ proximity ligation assay and immunostaining. To assess the effects of gain-
      and loss-of-function of beta-catenin, transfection experiments were performed to
      induce overexpression of the constitutively active form of beta-catenin (ca-beta
      catenin) and to block beta-catenin activity with small interfering RNA, in cells
      cotransfected with either wild-type PTHR1 or mutant forms (lacking binding to
      beta-catenin). Activation of the G protein alpha subunits G(alphas) and G(alphaq)
      in the cells was determined by measurement of the intracellular cAMP accumulation
      and intracellular Ca(2+) concentration, while activation of canonical Wnt
      pathways was assessed using a TOPflash reporter assay. RESULTS: In differentiated
      chondrocytes, beta-catenin physically interacted and colocalized with the cell
      membrane-specific region of PTHR-1 (584-589). Binding of beta-catenin to PTHR-1
      caused suppression of the G(alphas)/cAMP pathway and enhancement of the
      G(alphaq)/Ca(2+) pathway, without affecting the canonical Wnt pathway. Inhibition
      of Col10a1 messenger RNA (mRNA) expression by PTH was restored by overexpression
      of ca-beta-catenin, even after blockade of the canonical Wnt pathway, and Col10a1
      mRNA expression was further decreased by knockout of beta-catenin (via the Cre
      recombinase) in chondrocytes from beta-catenin-floxed mice. Mutagenesis analyses
      to block the binding of beta-catenin to PTHR1 caused an inhibition of chondrocyte
      hypertrophy markers. CONCLUSION: beta-catenin binds to the PTHR-1 C-tail and
      switches the downstream signaling pathway from G(alphas)/cAMP to
      G(alphaq)/Ca(2+), which is a possible mechanism by which chondrocyte hypertrophy
      may be regulated through the PTH/PTHrP signal independent of the canonical Wnt
      pathway.

PMID- 23124880
TI  - Characteristics and outcome of 16 periprosthetic shoulder joint infections.
AB  - PURPOSE: Shoulder arthroplasties are increasingly performed, but data on
      periprosthetic joint infections (PJI) in this anatomical position are limited. We
      retrospectively investigated the characteristics and outcome of shoulder PJI
      after primary arthroplasty from 1998 to 2010 in a single centre. METHODS:
      Periprosthetic joint infection was defined as periprosthetic purulence, presence
      of sinus tract or microbial growth. A Kaplan-Meier survival method was used to
      estimate relapse-free survival of prosthesis. RESULTS: From 1,571 primary
      shoulder prostheses, we evaluated 16 patients with a PJI at different stages,
      i.e, early (n = 4), delayed (n = 6) and late (n = 6) infections. The median
      patient age was 67 (range 53-86) years, and 69 % were females. The most commonly
      isolated microorganism was Propionibacterium acnes in 38 % of patients
      (monobacterial in four and polymicrobial in two patients). In 14 of the 16
      patients, surgical interventions consisting of debridement and implant retention
      (6 patients), exchange (7) and explantation (1) were performed. Four patients had
      a relapse of infection with P. acnes (n = 3) or Bacteroides fragilis (n = 1). The
      relapse-free survival of the prosthesis was 75 % (95 % confidence interval 46-90
      %) after 1 and 2 years, 100 % in six patients following the treatment algorithm
      for hip and knee PJI and 60 % in 10 patients not followed up. All but one of the
      relapses were previously treated without exchange of the prosthesis. CONCLUSIONS:
      As recommended for hip and knee PJI, we suggest treating shoulder PJI with a low
      grade infection by microorganisms such as P. acnes with an exchange of the
      prosthesis. Cohort studies are needed to verify our results.

PMID- 23124881
TI  - C-F bond activation of unactivated aliphatic fluorides: synthesis of fluoromethyl
      3,5-diaryl-2-oxazolidinones by desymmetrization of 2-aryl-1,3-difluoropropan-2
      ols.

PMID- 23124882
TI  - PulseNet China, a model for future laboratory-based bacterial infectious disease
      surveillance in China.
AB  - Surveillance is critical for the prevention and control of infectious disease.
      China's real-time web-based infectious disease reporting system is a
      distinguished achievement. However, many aspects of the current China Infectious
      Disease Surveillance System do not yet meet the demand for timely outbreak
      detection and identification of emerging infectious disease. PulseNet, the
      national molecular typing network for foodborne disease surveillance was first
      established by the Centers for Disease Control and Prevention of the United
      States in 1995 and has proven valuable in the early detection of outbreaks and
      tracing the pathogen source. Since 2001, the China CDC laboratory for bacterial
      pathogen analysis has been a member of the PulseNet International family; and has
      been adapting the idea and methodology of PulseNet to develop a model for a
      future national laboratory-based surveillance system for all bacterial infectious
      disease.We summarized the development progress for the PulseNet China system and
      discussed it as a model for the future of China's national laboratory-based
      surveillance system.

PMID- 23124883
TI  - Genome-wide association studies: inherent limitations and future challenges.
AB  - Genome-wide association studies (GWAS) have achieved great success in identifying
      genetic variants related to complex human diseases such as cancer and have
      provided valuable insights into their genetic architecture. Recently, GWAS is
      quite the fashion in China. However, there are issues related to its nature.
      Enormous work needs to be done in the post-GWAS era. Deep sequencing followed by
      functional studies will be needed to elucidate the underpinning biological
      mechanisms and further translate GWAS findings into medical practice. Along with
      pharmacogenomics, the success of GWAS in identifying genetic risk factors and
      genetic differences in drug response has been gradually enabling personalized
      medicine. In this article, we used hepatocellular carcinoma (HCC) as an example
      to demonstrate some of the inherent limitations and summarized future challenges
      of GWAS.

PMID- 23124884
TI  - Tramadol reinforces antidepressant effects of ketamine with increased levels of
      brain-derived neurotrophic factor and tropomyosin-related kinase B in rat
      hippocampus.
AB  - Ketamine exerts rapid and robust antidepressant properties in both animal models
      and depressed patients and tramadol possesses potential antidepressant effects.
      Brain-derived neurotrophic factor (BDNF) is an important biomarker for mood
      disorders and tropomyosin-related kinase B (TrkB) is a high affinity catalytic
      receptor for BDNF.We hypothesized that tramadol pretreatment might reinforce
      ketamine-elicited antidepressant effects with significant changes in hippocampal
      BDNF and TrkB levels in rats. Immobility time of rats receiving different
      treatment in the forced swimming test (FST) was observed. Levels of BDNF and TrkB
      in hippocampus were measured by enzyme linked immunosorbent assay. Results showed
      that tramadol (5 mg/kg) administrated alone neither elicited antidepressant
      effects nor altered BDNF or TrkB level. However, pretreatment with tramadol (5
      mg/kg) enhanced the ketamine (10 mg/kg) -elicited antidepressant effects and
      upregulated the BDNF and TrkB levels in hippocampus. In conclusion, tramadol
      pretreatment reinforces the ketamine-elicited antidepressant effects, which is
      associated with the increased levels of BDNF and TrkB in rat hippocampus.

PMID- 23124886
TI  - Finding a role for leptin in the regulation of the Th17 response in experimental
      arthritis: comment on the article by Deng et al. Reply.

PMID- 23124885
TI  - Role of the forkhead transcription factor FOXO-FOXM1 axis in cancer and drug
      resistance.
AB  - The forkhead transcription factors FOXO and FOXM1 have pivotal roles in
      tumorigenesis and in mediating chemotherapy sensitivity and resistance. Recent
      research shows that the forkhead transcription factor FOXM1 is a direct
      transcriptional target repressed by the forkhead protein FOXO3a, a vital
      downstream effector of the PI3K-AKT-FOXO signaling pathway. Intriguingly, FOXM1
      and FOXO3a also compete for binding to the same gene targets, which have a role
      in chemotherapeutic drug action and sensitivity. An understanding of the role and
      regulation of the FOXO-FOXM1 axis will impact directly on our knowledge of
      chemotherapeutic drug action and resistance in patients, and provide new insights
      into the design of novel therapeutic strategy and reliable biomarkers for
      prediction of drug sensitivity.

PMID- 23124887
TI  - First molecular characterization of visna/maedi viruses from naturally infected
      sheep in Turkey.
AB  - Recent worldwide serological and genetic studies of small ruminant lentiviruses
      (SRLV) have led to the description of new genotypes and the development of new
      diagnostic tests. This study investigated the detection and molecular
      characterization of visna/maedi virus (VMV) infection in serum and blood samples
      from pure and mixed sheep breeds acquired from different regions in Turkey using
      ELISA and PCR techniques. The prevalence of VMV was 67.8 % by ELISA and/or LTR
      PCR with both assays showing a medium level of agreement (kappa: 0.26; +/- 0.038
      CI). Positivity of VMV in sheep increased according to the age of the animal,
      although PCR positivity was higher than ELISA in young individuals. Phylogenetic
      analysis of 33 LTR sequences identified two distinct clades that were closely
      related to American and Greek LTR sequences. Phylogenetic analysis of 10 partial
      gag gene sequences identified A2, A3, A5, A9, A11 subtypes of genotype A SRLVs.
      In vitro culture of all isolates in fetal sheep lung cells (FSLC) showed a
      slow/low phenotype causing less or no lytic infection compared with infection
      with the WLC-1 American strain characterized by a rapid/highly lytic phenotype.
      Phylogenetic analysis revealed that Turkish VMV sequences preceded the
      establishment of American or Greek strains that were associated with the
      migration of sheep from the Middle East to Western Europe several centuries ago.
      This is the first study that describes Turkish VMV sequences with the molecular
      characterization of LTR and gag genes, and it strongly suggests that SRLV
      genotype A originated in Turkey.

PMID- 23124888
TI  - Molecular identification and phylogenetic study of coxsackievirus A24 variant
      isolated from an outbreak of acute hemorrhagic conjunctivitis in India in 2010.
AB  - An outbreak of acute hemorrhagic conjunctivitis (AHC) occured in India between
      August and October 2010. Molecular typing by RT-PCR and sequencing of a partial
      VP1 region identified coxsackievirus A24 variant (CV A24v) as the serotype
      involved in this outbreak. Phylogenetic analysis based on the VP1 and 3C genes
      revealed that CV A24v strains associated with the 2010 AHC outbreak in India were
      genetically similar to strains from Central and South America that caused
      outbreaks of AHC in Cuba between 2008 and 2009 and Brazil in 2009. The result
      shows that the Indian strain of CV A24v may be responsible for the recent AHC
      outbreak in Marseille, France, in 2012.

PMID- 23124889
TI  - An exploration of fixed and random effects selection for longitudinal binary
      outcomes in the presence of nonignorable dropout.
AB  - We explore a Bayesian approach to selection of variables that represent fixed and
      random effects in modeling of longitudinal binary outcomes with missing data
      caused by dropouts. We show via analytic results for a simple example that
      nonignorable missing data lead to biased parameter estimates. This bias results
      in selection of wrong effects asymptotically, which we can confirm via
      simulations for more complex settings. By jointly modeling the longitudinal
      binary data with the dropout process that possibly leads to nonignorable missing
      data, we are able to correct the bias in estimation and selection. Mixture priors
      with a point mass at zero are used to facilitate variable selection. We
      illustrate the proposed approach using a clinical trial for acute ischemic
      stroke.

PMID- 23124890
TI  - A joint experimental and computational search for authentic nano-electrocatalytic
      effects: electrooxidation of nitrite and L-ascorbate on gold nanoparticle
      modified glassy carbon electrodes.
AB  - The investigation of electrocatalytic nanoeffects is tackled via joint
      electrochemical measurements and computational simulations. The cyclic
      voltammetry of electrodes modified with metal nanoparticles is modeled
      considering the kinetics of the electrochemical process on the bulk materials of
      the different regions of the electrode, that is, the substrate (glassy carbon)
      and the nanoparticles (gold). Comparison of experimental and theoretical results
      enables the detection of changes in the electrode kinetics at the nanoscale due
      to structural and/or electronic effects. This approach is applied to the
      experimental assessment of electrocatalytic effects by gold nanoparticles (Au
      NPs) in the electrooxidation of nitrite and L-ascorbate. Glassy carbon electrode
      is modified with Au NPs via seed-mediated growth method. Divergence between the
      kinetics of these processes on gold macroelectrodes and gold nanoparticles is
      examined. Whereas claimed catalytic effects are not observed in the
      electrooxidation of nitrite, electrocatalytic nanoeffects are verified in the
      case of L-ascorbate. This is probably due to that the electron transfer process
      follows an adsorptive mechanism. The combination of simulation with experiments
      is commended as a general strategy of authentification, or not, of
      nanoelectrocatalytic effects.

PMID- 23124891
TI  - DSM-5 field survey: hair-pulling disorder (trichotillomania).
AB  - BACKGROUND: The aim of this multisite field survey was to examine the DSM-IV-TR
      criteria, proposed DSM-5 diagnostic criteria, as well as a number of possible
      additional diagnostic criteria, in patients with hair-pulling disorder (HPD, or
      trichotillomania). METHODS: Four sites were involved. Participants older than 10
      years of age, male or female, with hair-pulling symptoms in the last 4 weeks were
      included. Participants were assessed with two modules based on the Structured
      Clinical Interview for DSM (SCID-I/P), which addressed the DSM-IV-TR criteria set
      as well as proposed DSM-5 diagnostic criteria for HPD, respectively. Additional
      questions were established to test other possible diagnostic criteria. RESULTS:
      Eighty-four (79 female, 5 male, 83 adult) participants with current hair-pulling
      symptoms were included. All of these participants had recurrent hair-pulling and
      most (n = 82 [98%]) reported repeated attempts to decrease or stop hair-pulling,
      and 70 (n = 70 [83%]) met the clinical significance criterion. Diagnostic
      criteria focused on "urge," "tension," "need," "drive," or "impulse" to pull, or
      pleasure, gratification or relief during or after pulling, were endorsed by many,
      but not all. Individuals who did endorse such criteria had significantly more
      severe hair-pulling symptoms. CONCLUSIONS: These data support the proposed
      diagnostic criteria for HPD in adults. Although most adult patients have urges to
      pull or experience a sense of relief on pulling, as in the case of skin-picking
      disorder, such phenomena are not universal and so should not be included in the
      diagnostic criteria. An additional criterion focused on repeated attempts to
      decrease or stop hair-pulling seems warranted.

PMID- 23124893
TI  - Gene expression of carnosine-related enzymes and transporters in skeletal muscle.
AB  - Chronic oral beta-alanine supplementation can elevate muscle carnosine (beta
      alanyl-L-histidine) content and improve high-intensity exercise performance.
      However, the regulation of muscle carnosine levels is poorly understood. The
      uptake of the rate-limiting precursor beta-alanine and the enzyme catalyzing the
      dipeptide synthesis are thought to be key steps. The aims of this study were to
      investigate the expression of possible carnosine-related enzymes and transporters
      in both human and mouse skeletal muscle in response to carnosine-altering
      stimuli. Human gastrocnemius lateralis and mouse tibialis anterior muscle samples
      were subjected to HPLC and qPCR analysis. Mice were subjected to chronic oral
      supplementation of beta-alanine and carnosine or to orchidectomy (7 and 30 days,
      with or without testosterone replacement), stimuli known to, respectively,
      increase and decrease muscle carnosine and anserine. The following carnosine
      related enzymes and transporters were expressed in human and/or mouse muscles:
      carnosine synthase (CARNS), carnosinase-2 (CNDP2), the carnosine/histidine
      transporters PHT1 and PHT2, the beta-alanine transporters TauT and PAT1, beta
      alanine transaminase (ABAT) and histidine decarboxylase (HDC). Six of these genes
      showed altered expression in the investigated interventions. Orchidectomy led to
      decreased muscle carnosine content, which was paralleled with decreased TauT
      expression, whereas CARNS expression was surprisingly increased. Beta-alanine
      supplementation increased both muscle carnosine content and TauT, CARNS and ABAT
      expression, suggesting that muscles increase beta-alanine utilization through
      both dipeptide synthesis (CARNS) and deamination (ABAT) and further oxidation, in
      conditions of excess availability. Collectively, these data show that muscle
      carnosine homeostasis is regulated by nutritional and hormonal stimuli in a
      complex interplay between related transporters and enzymes.

PMID- 23124894
TI  - Apoptosis of the reduced enamel epithelium and its implications for bone
      resorption during tooth eruption.
AB  - Bone remodeling, the selective deposition and resorption of bone, is an important
      cause of tooth eruption. During tooth eruption, reduced enamel epithelia of the
      enamel organ interact with follicle cells to recruit osteoclasts for bone
      remodeling. However, little is known about the relationship between cellular
      activity of reduced enamel epithelium and bone resorption during tooth eruption.
      The purpose of this study was to investigate the effect of apoptosis in reduced
      enamel epithelium on osteoclastogenesis and its implications for bone resorption.
      We have analyzed erupting mandibular molars in mice by TdT-mediated dUTP-biotin
      nick end labeling assay, tartrate-resistant acid phosphatase (TRAP) staining, and
      immunohistochemistry. TRAP-positive cells were detected in the osteoclasts near
      both the buccal and lingual sides of tooth socket at postnatal day 0 (PN0). They
      significantly increased until PN3 and decreased thereafter as the tooth erupted.
      Interestingly, apoptosis was barely detected in the reduced enamel epithelium at
      PN3 but clearly at PN7. A few apoptotic cells were also investigated within the
      dental follicle surrounding developing tooth at PN7 and PN10. We observed
      apoptotic osteoblast-lineage cells along the inner margin of alveolar bone facing
      the buccal cusp and at the base of the bony crypt at PN3 decreasing until PN10.
      In contrast, expression levels of bone sialoprotein increased at PN10 compared to
      levels at PN3. These results suggest that apoptosis of reduced enamel epithelium
      resulted in a reduction of osteoclast activity and of bone resorption mediated by
      dental follicle during tooth eruption.

PMID- 23124895
TI  - Combining cell lines to optimize isolation of human enterovirus from clinical
      specimens: report of 25 years of experience.
AB  - Cell culture is still the gold standard for the diagnosis of human enteroviruses
      (HEVs) although molecular techniques are required for detection of some
      serotypes. Due to the diversity of HEVs, a single cell line is not susceptible to
      all serotypes, and several lines are required to optimize the isolation of HEVs.
      In this study, the results of HEV isolation during the last 25 years are
      reported. A total of 1,192 HEVs were isolated and isolation rates varied
      depending on the cell line used. MRC5 cells yielded the best results (70.7%),
      followed by A549 cells (52.6%), RD cells (37.5%), and HEp-2 cells (29.7%). A
      total of 521 HEVs were characterized, and HEV-B was the most frequent species
      (81%). Polioviruses (PV) and HEV-A were isolated less frequently (17% and 1%,
      respectively). None of the cell lines detected all the enteroviruses. MRC5 cells
      were the most susceptible for isolation of echoviruses (85.7%) and PVs (85.4%),
      whereas HEp2 was the most susceptible for Coxsackieviruses B (82.6%). Some
      serotypes were isolated in one cell line only. 40.5% of echoviruses were isolated
      in MRC5 cells whereas 42.3% and 23.9% of Coxsackieviruses B were isolated in RD
      cells and HEp2 cells, respectively. Although A549 cells did not achieve the best
      performance for any enterovirus serotypes, they isolated 52.6% of the total HEVs.
      In view of these results, MRC5 cells, A549 cells, and RD cells should be combined
      to optimize isolation of HEVs.

PMID- 23124892
TI  - Increasing use of atypical antipsychotics and anticonvulsants during pregnancy.
AB  - PURPOSE: To quantify maternal use of atypical antipsychotics, typical
      antipsychotics, anticonvulsants, and lithium during pregnancy. METHODS: Tennessee
      birth and death records were linked to Tennessee Medicaid data to conduct a
      retrospective cohort study of 296,817 women enrolled in Tennessee Medicaid
      throughout pregnancy who had a live birth or fetal death from 1985 to 2005.
      RESULTS: During the study time period, the adjusted rate of use of any study
      medication during pregnancy increased from nearly 14 to 31 per 1000 pregnancies
      (beta = 0.08, 95% CI = 0.07, 0.09). Significant increases were reported in use of
      anticonvulsants alone among mothers with pain and other psychiatric disorders,
      atypical antipsychotics alone among mothers with bipolar disorders,
      schizophrenia, unipolar depressive disorders, and other psychiatric disorders,
      and more than one studied medication for mothers with epilepsy, pain disorders,
      bipolar disorders, unipolar depressive disorders, and other psychiatric
      disorders. Significant decreases were reported in use of lithium alone and
      typical antipsychotics alone for all clinically meaningful diagnosis groups.
      CONCLUSIONS: There was a substantial increase in use of atypical antipsychotics
      alone, anticonvulsants alone, and medications from multiple studied categories
      among Tennessee Medicaid-insured pregnant women during the study period. Further
      examination of the maternal and fetal consequences of exposure to these
      medications during pregnancy is warranted.

PMID- 23124896
TI  - Retention in the endoplasmic reticulum is the underlying mechanism of some
      hereditary haemorrhagic telangiectasia type 2 ALK1 missense mutations.
AB  - Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disease
      characterised by vascular dysplasia and increased bleeding that affect 1 in 5,000
      people world-wide. Pathology is linked to mutations in genes encoding components
      of the heteromeric transforming growth factor-beta receptor (TGF-beta) and SMAD
      signalling pathway. Indeed HHT1 and HHT2 result from mutations in the genes
      encoding endoglin and activin-like kinase 1 (ALK1), TGF-beta receptor components.
      However, the fundamental cellular defects underlying HHT is poorly understood.
      Previously using confocal microscopy and N-glycosylation analysis, we found
      evidence that defective trafficking of endoglin from the endoplasmic reticulum
      (ER) to the plasma membrane is a mechanism underlying HHT1 in some patients. In
      this study, we used confocal microscopy to investigate whether a similar
      mechanism contributes to HHT2 pathology. To do this we expressed wild-type ALK1
      and a number of HHT2 patient mutant variants as C-terminally tagged EGFP fusion
      proteins and tested their localisation in HeLa cells. We found that wild-type
      ALK1-EGFP was targeted predominantly to the plasma membrane, as evidenced by its
      colocalisation with the  co-expressed HA-tagged endoglin. However, we found that
      in the majority of cases analysed the HHT2 patient mutant protein was retained
      within the ER as indicated by their colocalisation with the ER resident marker
      (calnexin) and lack of colocalisation with cell surface associated HA-endoglin.
      We conclude that defective trafficking and retention in the ER of mutant ALK1
      protein is a possible mechanism of HHT2 in some patients.

PMID- 23124898
TI  - Stress-induced stabilization of crystals in shape memory natural rubber.
AB  - In contrast to all known shape memory polymers, the melting temperature of
      crystals in shape memory natural rubber (SMNR) can be greatly manipulated by the
      application of external mechanical stress. As shown previously, stress
      perpendicular to the prior programming direction decreases the melting
      temperature by up to 40 K. In this study, we investigated the influence of
      mechanical stress parallel to prior stretching direction during programming on
      the stability of the elongation-stabilizing crystals. It was found that parallel
      stress stabilizes the crystals, which is indicated by linear increase of the
      trigger temperature by up to 17 K. The crystal melting temperature can be
      increased up to 126.5  degrees C under constrained conditions as shown by X-ray
      diffraction measurements.

PMID- 23124897
TI  - INMAP, a novel truncated version of POLR3B, represses AP-1 and p53
      transcriptional activity.
AB  - INMAP was first identified as an interphase nucleus and mitotic apparatus
      associated protein that plays essential roles in the formation of the spindle and
      cell-cycle progression. Here, we report that INMAP might be conserved from
      prokaryotes to humans, is a truncated version of the RNA polymerase III subunit B
      POLR3B, and is up-regulated in several human cancer cell lines including HeLa,
      Bel-7402, HepG2 and BGC-823. Deletion analysis revealed that the 209-290 amino
      acid region is necessary for the punctate distribution of INMAP in the nucleus.
      Furthermore, over-expression of INMAP inhibited the transcriptional activities of
      p53 and AP-1 in a dose-dependent manner. These results suggest that INMAP may
      function through the p53 and AP-1 pathways, thus providing a possible link of its
      activity with tumourigenesis. Integrating our data and those in previous studies,
      it can be concluded that INMAP plays dual functional roles in the coordination of
      mitotic kinetics with gene expression as well as in cell-fate determination and
      proliferation.

PMID- 23124899
TI  - Laminar segregation of GABAergic neurons in the avian nucleus isthmi pars
      magnocellularis: a retrograde tracer and comparative study.
AB  - The isthmic complex is part of a visual midbrain circuit thought to be involved
      in stimulus selection and spatial attention. In birds, this circuit is composed
      of the nuclei isthmi pars magnocellularis (Imc), pars parvocellularis (Ipc), and
      pars semilunaris (SLu), all of them reciprocally connected to the ipsilateral
      optic tectum (TeO). The Imc conveys heterotopic inhibition to the TeO, Ipc, and
      SLu via widespread gamma-aminobutyric acid (GABA)ergic axons that allow global
      competitive interactions among simultaneous sensory inputs. Anatomical studies in
      the chick have described a cytoarchitectonically uniform Imc nucleus containing
      two intermingled cell types: one projecting to the Ipc and SLu and the other to
      the TeO. Here we report that in passerine species, the Imc is segregated into an
      internal division displaying larger, sparsely distributed cells, and an external
      division displaying smaller, more densely packed cells. In vivo and in vitro
      injections of neural tracers in the TeO and the Ipc of the zebra finch
      demonstrated that neurons from the external and internal subdivisions project to
      the Ipc and the TeO, respectively, indicating that each Imc subdivision contains
      one of the two cell types hodologically defined in the chick. In an extensive
      survey across avian orders, we found that, in addition to passerines, only
      species of Piciformes and Rallidae exhibited a segregated Imc, whereas all other
      groups exhibited a uniform Imc. These results offer a comparative basis to
      investigate the functional role played by each Imc neural type in the competitive
      interactions mediated by this nucleus.

PMID- 23124900
TI  - Revisiting flow-chemiluminescence techniques: pharmaceutical analysis.
AB  - The state of the art in flow-chemiluminescence (flow-CL) technique for automated
      pharmaceutical analysis is reviewed. Flow-CL approaches have become powerful and
      promising tools for pharmaceutical screening in recent years due to their
      simplicity, low cost and high sensitivity. Because of these advantages, these
      methods have been widely used for pharmaceutical analysis in recent years. The
      literature reviewed covers papers of analytical interest that appeared between
      2007 and mid-2012 and have been divided into several sections based on
      fundamental types of CL systems employed. Furthermore, entries have been
      summarized alphabetically in tabular form giving details of analytical figures of
      merit of the methods.

PMID- 23124901
TI  - Reply: Expression of free HLA class I heavy chains in an immune-privileged site:
      comment on the article by Taurog et al.

PMID- 23124902
TI  - Multivalent proteoglycan modulation of FGF mitogenic responses in perivascular
      cells.
AB  - Sprouting of angiogenic perivascular cells is thought to be highly dependent upon
      autocrine and paracrine growth factor stimulation. Accordingly, we report that
      corneal angiogenesis induced by ectopic FGF implantation is strongly impaired in
      NG2/CSPG4 proteoglycan (PG) null mice known to harbour a putative deficit in
      pericyte proliferation/mobilization. Conversely, no significant differences were
      seen between wild type and knockout corneas when VEGF was used as an angiocrine
      factor. Perturbed responsiveness of NG2-deficient pericytes to paracrine and
      autocrine stimulation by several FGFs could be confirmed in cells isolated from
      NG2 null mice, while proliferation induced by other growth factors was equivalent
      in wild type and knockout cells. Identical results were obtained after siRNA
      mediated knock-down of NG2 in human smooth muscle-like cell lines, as also
      demonstrated by the decreased levels of FGF receptor phosphorylation detected in
      these NG2 deprived cells. Binding assays with recombinant proteins and molecular
      interactions examined on live cells asserted that FGF-2 bound to NG2 in a
      glycosaminoglycan-independent, core protein-mediated manner and that the PG was
      alone capable of retaining FGF-2 on the cell membrane for subsequent receptor
      presentation. The use of dominant-negative mutant cells, engineered by combined
      transduction of NG2 deletion constructs and siRNA knock-down of the endogenous
      PG, allowed us to establish that the FGF co-receptor activity of NG2 is entirely
      mediated by its extracellular portion. In fact, forced overexpression of the NG2
      ectodomain in human smooth muscle-like cells increased their FGF-2-induced
      mitosis and compensated for low levels of FGF receptor surface expression, in a
      manner equivalent to that produced by overexpression of the full-length NG2. Upon
      FGF binding, the cytoplasmic domain of NG2 is phosphorylated, but there is no
      evidence that this event elicits signal transductions that could bypass the FGFR
      mediated ones. Pull-down experiments, protein-protein binding assays and flow
      cytometry FRET coherently revealed an elective ligand-independent association of
      NG2 with FGFR1 and FGFR3. The NG2 cooperation with these receptors was also
      corroborated functionally by the outcome of FGF-2 treatments of cells engineered
      to express diverse NG2/FGFR combinations. Comprehensively, the findings suggest
      that perivascular NG2 may serve as a dual modulator of the
      availability/accessibility of FGF at the cell membrane, as well as the resulting
      FGFR transducing activity.

PMID- 23124903
TI  - N-heterocyclic-carbene-catalyzed asymmetric oxidative hetero-Diels-Alder
      reactions with simple aliphatic aldehydes.

PMID- 23124905
TI  - Kinetic properties of a novel Fusarium solani (phospho)lipase: a monolayer study.
AB  - Using the monomolecular film technique, we studied interfacial properties of
      Fusarium solani lipase (FSL). This lipolytic enzyme was found to be unique among
      the fungal lipases possessing not only a lipase activity but also a high
      phospholipase one.The FSL was able to hydrolyze dicaprin films at various surface
      pressures. The surface pressure dependency, the stereospecificity, and the
      regioselectivity of FSL were performed using optically pure stereoisomers of
      diglyceride (1,2-sn- dicaprin and 2,3-sn-dicaprin) and a prochiral isomer (1,3-sn
      dicaprin) spread as monomolecular films at the air-water interface. The FSL
      prefers adjacent ester groups of the diglyceride isomers (1,2-sn-dicaprin and 2,3
      sn-dicaprin) at low and high surface pressures. Furthermore, FSL was found to be
      markedly stereospecific for the sn-1 position of the 1,2-sn-enantiomer of
      dicaprin at both low and high surface pressures.Moreover, FSL shows high
      activities on phospholipids monolayers. However, this enzyme displays high
      preference to zwitterionic phospholipids compared to the negatively charged ones.

PMID- 23124904
TI  - Qualitative development of the PROMIS(R) pediatric stress response item banks.
AB  - OBJECTIVE: To describe the qualitative development of the Patient-Reported
      Outcome Measurement Information System (PROMIS(r)) Pediatric Stress Response item
      banks. METHODS: Stress response concepts were specified through a literature
      review and interviews with content experts, children, and parents. A library
      comprising 2,677 items derived from 71 instruments was developed. Items were
      classified into conceptual categories; new items were written and redundant items
      were removed. Items were then revised based on cognitive interviews (n = 39
      children), readability analyses, and translatability reviews. RESULTS: 2
      pediatric Stress Response sub-domains were identified: somatic experiences (43
      items) and psychological experiences (64 items). Final item pools cover the full
      range of children's stress experiences. Items are comprehensible among children
      aged >=8 years and ready for translation. CONCLUSIONS: Child- and parent-report
      versions of the item banks assess children's somatic and psychological states
      when demands tax their adaptive capabilities.

PMID- 23124906
TI  - Comparison of polymyxin B with other antimicrobials in the treatment of
      ventilator-associated pneumonia and tracheobronchitis caused by Pseudomonas
      aeruginosa or Acinetobacter baumannii.
AB  - PURPOSE: This study was designed to compare the efficacy of polymyxin B with
      other antimicrobials in the treatment of ventilator-associated pneumonia (VAP)
      and tracheobronchitis (VAT) by Pseudomonas aeruginosa or Acinetobacter baumannii.
      METHODS: A prospective cohort study was performed. Patients >18 years of age with
      the diagnosis of VAP or VAT who received appropriate therapy for >48 h were
      analyzed. The primary outcome was 30-day mortality. Clinical covariates were
      assessed and compared between the groups. RESULTS: A total of 67 episodes were
      analyzed: 45 (67 %) treated with polymyxin B and 22 (33 %) with comparators. The
      crude 30-day mortality was 53 % (24 of 45) in the polymyxin B group and 27 % (6
      of 22) in the comparator group (P = 0.08). Multivariable analysis using Cox
      regression models indicated that polymyxin B treatment was independently
      associated with increased mortality. CONCLUSIONS: Polymyxin B treatment in the
      currently recommended dosage may be inferior to other drugs in the treatment of
      VAP and VAT caused by organisms tested as susceptible in vitro to this agent.

PMID- 23124907
TI  - Why is antimicrobial de-escalation under-prescribed for urinary tract infections?
AB  - PURPOSE: To assess the frequency of de-escalation in inpatients treated for
      community-acquired urinary tract infection and the frequency of conditions
      legitimating not de-escalating therapy. METHODS: A retrospective study of
      inpatients (age >15 years) at a large academic hospital who were empirically
      treated for urinary tract infections due to Escherichia coli susceptible to at
      least one of the following antibacterial agents: amoxicillin, co-amoxiclav, and
      cotrimoxazole. De-escalation was defined as the replacement of the empirical
      broad-spectrum therapy by amoxicillin, co-amoxiclav, or cotrimoxazole. RESULTS:
      Eighty patients were included. De-escalation was prescribed for 32 of 69 patients
      for whom it was possible from both a bacteriological and clinical point of view
      (46 %, 95 % CI, 34-59 %). Initial treatment was switched to amoxicillin (n = 21),
      co-amoxiclav (n = 2), or cotrimoxazole (n = 8). Thirteen conditions justifying
      not de-escalating antibacterial therapy were detected in 11 of 48 patients who
      were not de-escalated (23 %, 95 % CI, 12-37 %): shock, n = 5; renal abscess, n =
      1; obstructive uropathy, n = 4; bacterial resistance or clinical contraindication
      to both cotrimoxazole and beta-lactams, n = 3. CONCLUSIONS: De-escalation is
      under-prescribed for urinary tract infections. Omission of de-escalation is
      seldom legitimate. Interventions aiming to de-escalate antibacterial therapy for
      UTIs should be actively implemented.

PMID- 23124908
TI  - The Austrian syndrome: a case report and review of the literature.
AB  - A 61-year-old man presented with fever and altered mental status. He was
      intubated for respiratory distress and was found to have multilobar pneumonia for
      which antibiotic therapy was instituted. However, his mental status continued to
      deteriorate despite appropriate antibiotic therapy for his pneumonia. The results
      from lumar puncture revealed meningitis and endocarditis was evident on a trans
      esophageal echocardiogram. His blood and respiratory cultures grew Streptococcus
      pneumoniae. The patient was diagnosed with Austrian syndrome. After appropriate
      changes to his antibiotic regimen and an aortic valve replacement, he recovered
      and was discharged.

PMID- 23124909
TI  - Binary Janus porous coordination polymer coatings for sensor devices with tunable
      analyte affinity.
AB  - Janus MOF: thin films consisting of non-centrosymmetric heterostructured metal
      organic frameworks (MOFs) were fabricated directly on quartz-crystal microbalance
      (QCM) sensor devices. Depending on the spatial configuration of two frameworks,
      the thin MOF films could tune the affinity for analytes, thus giving high
      selectivity to the QCM sensors.

PMID- 23124910
TI  - Neuronal control of pedal sole cilia in the pond snail Lymnaea stagnalis
      appressa.
AB  - 5-HT (serotonin) is a ubiquitous neurotransmitter that produces ciliary beating
      in gastropods when applied topically, but ciliary beating caused by gastropod
      serotonergic neurons has been described in only three neuron pairs. We extend
      these results to the North American Lymnaea stagnalis appressa, which is a
      different species from the European Lymnaea stagnalis. We describe a non
      serotonergic neuron pair, PeV1, which accelerates pedal sole mucociliary
      transport and a serotonergic neuron pair, PeD7, which slows mucociliary
      transport. We compare and discuss development and identified neurons in L. s.
      appressa and in L. stagnalis, which have homologs to L. s. appressa PeD7 and PeV1
      neurons. In addition to PeD7 and PeV1 neurons, we test neurons immunoreactive to
      Tritonia pedal peptide antibodies with negative results for mucociliary
      transport. In characterizing PeD7 and PeV1 neurons, we find that PeV1 does not
      excite PeD7. In semi-intact preparations, a strong increase in PeD7 neuron
      activity occurs during tactile stimulation, but V1 neurons are inhibited during
      tactile stimulation. Following tactile stimulation, PeV1 neurons show strong
      activity. This suggests a distinct difference in function of the two neuron
      pairs, which both have their axons overlying pedal sole ciliary cells.
      Application of 5-HT to the pedal sole initiates mucociliary transport in 1.4-1.9
      s with a time course similar to that seen when stimulating a PeV1 neuron. This
      result appears to be through a 5-HT(1A)-like receptor on the pedal sole. We
      describe a possible external source of 5-HT on the pedal sole from 5-HT
      immunoreactive granules that are released with mucus.

PMID- 23124911
TI  - Genome-wide profiling of bone reveals differentially methylated regions in
      osteoporosis and osteoarthritis.
AB  - OBJECTIVE: To determine genome-wide methylation profiles of bone from patients
      with hip osteoarthritis (OA) and those with osteoporotic (OP) hip fractures.
      METHODS: Trabecular bone pieces were obtained from the central part of the
      femoral head of 27 patients with hip fractures and 26 patients with hip OA. DNA
      was isolated, and methylation was explored with Illumina methylation arrays. RNA
      was extracted, pooled, and deep-sequenced to obtain the whole transcriptome.
      Differentially methylated regions were identified, and connections between genes
      with differentially methylated regions were explored by pathway and text-mining
      analyses. RESULTS: After quality control, methylation of 23,367 CpG sites (13,463
      genes) was analyzed. There was a genome-wide inverse relationship between
      methylation and gene expression in both patient groups. Comparison of OP and OA
      bones revealed 241 CpG sites, located in 228 genes, with significant differences
      in methylation (false discovery rate<0.05). Of them, 217 were less methylated in
      OP than in OA. The absolute methylation differences were >5% in 128 CpG sites and
      >10% in 45 CpG sites. The differentially methylated genes were enriched for
      association with bone traits in the genome-wide association study catalog.
      Pathway analysis and text-mining analysis with Gene Relationships Across
      Implicated Loci software revealed enrichment in genes participating in
      glycoprotein metabolism or cell differentiation, and particularly in the homeobox
      superfamily of transcription factors. CONCLUSION: Genome-wide methylation
      profiling of bone samples revealed differentially methylated regions in OP and
      OA. These regions were enriched in genes associated with cell differentiation and
      skeletal embryogenesis, such as those in the homeobox superfamily, suggesting the
      existence of a developmental component in the predisposition to these disorders.

PMID- 23124912
TI  - Pervasive refusal syndrome among inpatient asylum-seeking children and
      adolescents: a follow-up study.
AB  - BACKGROUND: Pervasive refusal syndrome (PRS) is a rare but severe condition,
      characterised by social withdrawal and a pervasive active refusal in terms of
      eating, mobilisation, speech and personal hygiene. PRS has been proposed as a new
      diagnostic entity in child and adolescent psychiatry, although the diagnostic
      criteria are debated. In the past 10 years there has been an increase in PRS
      symptoms among asylum-seeking children and adolescents in Sweden. Here, we
      describe five cases of PRS among asylum-seeking children and adolescents. METHOD:
      Three females and 2 males, 7-17 years of age with the clinical picture of PRS,
      treated as inpatients at the Department of Child and Adolescent Psychiatry,
      Malmo, Sweden, 2002-2010, were analysed on the basis of their medical records.
      Subjects were diagnosed using previously suggested criteria for PRS. At follow
      up, a semi-structured interview focusing on the inpatient stay and current status
      was performed. The subjects were assessed with Global Assessment of Functioning
      (GAF) and self-rating questionnaires regarding depression and post-traumatic
      stress disorder (PTSD). RESULTS: The pattern of refusal varied among the five
      subjects. All subjects originated from former Soviet republics, indicating a
      possible cultural factor. Mean period of inpatient treatment was 5 months. All
      subjects received intense nursing and were treated with nasogastric tube feeding.
      Parents were involved and were given support and instructions. All subjects
      gradually improved after receiving permanent residency permits. Depression and
      PTSD were co-morbid states. At follow-up, 1-8 years after discharge, all subjects
      were recovered. CONCLUSION: Although a severe condition, our five cases suggest a
      good prognosis for PRS among asylum-seeking children and adolescents.

PMID- 23124914
TI  - The efficacy of a topical sialogogue spray containing 1% malic acid in patients
      with antidepressant-induced dry mouth: a double-blind, randomized clinical trial.
AB  - BACKGROUND: One of the most important antidepressants side effects is dry mouth.
      The aim of this study was to evaluate the clinical efficacy of a topical
      sialogogue spray containing 1% malic acid on patients affected by dry mouth
      caused by antidepressants drug. MATERIALS AND METHODS: This research took the
      form of a double-blind, randomized clinical trial at Faculty of Dentistry of
      University of Granada (Spain). Seventy participants with antidepressant-induced
      dry mouth were divided into two groups: for the first "intervention group" (35
      subjects) a topical sialogogue spray (1% malic acid) was applied, while for the
      second "control group" (35 subjects), a placebo spray was applied; for both
      groups, the sprays were applied on demand during 2 weeks. The dry mouth
      questionnaire (DMQ) was used to evaluate dry mouth symptoms before and after
      product/placebo application. Unstimulated and stimulated salivary flows rates,
      before and after application, were measured. RESULTS: Dry mouth symptoms improved
      after 1% malic acid topical spray application (p < .05). After 2 weeks of 1%
      malic acid application, unstimulated and stimulated salivary flows rates
      increased significantly (p < .05). CONCLUSIONS: A sialogogue spray containing 1%
      malic acid improved dry mouth feeling of the patients suffering antidepressant
      induced dry mouth and increased unstimulated and stimulated salivary flows rates.

PMID- 23124913
TI  - Treatment for chronic heart failure in the elderly: current practice and
      problems.
AB  - Treatment for chronic heart failure (CHF) is strongly focused on evidence-based
      medicine. However, large trials are often far away from the "real world" of
      geriatric patients and their messages are poorly transferable to the clinical
      management of CHF elderly patients. Precipitating factors and especially non
      cardiac comorbidity may decompensate CHF in the elderly. More importantly, drugs
      of first choice, such as angiotensin-converting enzyme inhibitors and beta
      blockers, are still underused and effective drugs on diastolic dysfunction are
      not available. Poor adherence to therapy, especially for cognitive and depression
      disorders, worsens the management. Electrical therapy is indicated, but attention
      to the older age groups with reduced life expectancy has to be paid. Physical
      exercise, stem cells, gene delivery, and new devices are encouraging, but
      definitive results are still not available. Palliative care plays a key role to
      the end-stage of the disease. Follow-up of CHF elderly patient is very important
      but tele-medicine is the future. Finally, self-care management, caregiver
      training, and multidimensional team represent the critical point of the treatment
      for CHF elderly patients.

PMID- 23124916
TI  - Prevention and treatment of vitamin D deficiency.
AB  - Vitamin D insufficiency and deficiency are widespread in many countries. We
      review the evidence pertaining to its prevention and treatment. Deficiency may be
      adequately treated with many different therapeutic regimens of either
      cholecalciferol or ergocalciferol, owing to the high therapeutic index of both
      compounds. Nevertheless, the current evidence suggests that regular dosing with
      oral cholecalciferol (e.g., 60,000 IU weekly) may have slight advantages over
      other regimens when replenishing vitamin D stores following deficiency. For long
      term supplementation, smaller regular doses, such as cholecalciferol 1,000 IU
      daily, or 10,000 IU weekly, are suitable. Giving reliable and specific advice
      about appropriate sunlight exposure remains difficult because of differing
      interindividual skin pigmentation and variable sunlight UVB content at different
      latitudes, at different times of year, and in different terrestrial environments.

PMID- 23124915
TI  - Lipidomic profiling of chylomicron triacylglycerols in response to high fat
      meals.
AB  - Using lipidomic methodologies the impact that meal lipid composition and
      metabolic syndrome (MetS) exerts on the postprandial chylomicron triacylglycerol
      (TAG) response was examined. Males (9 control; 11 MetS) participated in a
      randomised crossover trial ingesting two high fat breakfast meals composed of
      either dairy-based foods or vegetable oil-based foods. The postprandial lipidomic
      molecular composition of the TAG in the chylomicron-rich (CM) fraction was
      analysed with tandem mass spectrometry coupled with liquid chromatography to
      profile CM TAG species and targeted TAG regioisomers. Postprandial CM TAG
      concentrations were significantly lower after the dairy-based foods compared with
      the vegetable oil-based foods for both control and MetS subjects. The CM TAG
      response to the ingested meals involved both significant and differential
      depletion of TAG species containing shorter- and medium-chain fatty acids (FA)
      and enrichment of TAG molecular species containing C16 and C18 saturated,
      monounsaturated and diunsaturated FA. Furthermore, there were significant changes
      in the TAG species between the food TAG and CM TAG and between the 3- and 5-h
      postprandial samples for the CM TAG regioisomers. Unexpectedly, the postprandial
      CM TAG concentration and CM TAG lipidomic responses did not differ between the
      control and MetS subjects. Lipidomic analysing of CM TAG molecular species
      revealed dynamic changes in the molecular species of CM TAG during the
      postprandial phase suggesting either preferential CM TAG species formation and/or
      clearance.

PMID- 23124917
TI  - Revealing rotational modes of functionalized gold nanorods on live cell
      membranes.
AB  - A full understanding of cell mechanics requires knowledge of both translational
      and rotational dynamics. The single particle orientation and rotational tracking
      (SPORT) technique is combined here with correlation analysis to identify the
      fundamental rotational modes: in-plane rotation and out-of-plane tilting, as well
      as other more complex rotational patterns, from the vast image data captured at a
      temporal resolution of 5 ms for single gold nanorod probes in live cell imaging
      experiments. The unique capabilities of visualizing and understanding rotational
      motions of functional nanoparticles on live cell membranes allow correlation of
      the rotational and translational dynamics in unprecedented detail and provide new
      insights into complex membrane processes. Particles with functionalized surfaces,
      which interact with the membrane in fundamentally different ways, can exhibit
      distinct rotational modes and are, for the first time, directly visualized, and
      these show the early events for membrane approach and attachment.

PMID- 23124918
TI  - A computational model of visually guided locomotion in lamprey.
AB  - This study addresses mechanisms for the generation and selection of visual
      behaviors in anamniotes. To demonstrate the function of these mechanisms, we have
      constructed an experimental platform where a simulated animal swims around in a
      virtual environment containing visually detectable objects. The simulated animal
      moves as a result of simulated mechanical forces between the water and its body.
      The undulations of the body are generated by contraction of simulated muscles
      attached to realistic body components. Muscles are driven by simulated
      motoneurons within networks of central pattern generators. Reticulospinal
      neurons, which drive the spinal pattern generators, are in turn driven directly
      and indirectly by visuomotor centers in the brainstem. The neural networks
      representing visuomotor centers receive sensory input from a simplified retina.
      The model also includes major components of the basal ganglia, as these are
      hypothesized to be key components in behavior selection. We have hypothesized
      that sensorimotor transformation in tectum and pretectum transforms the place
      coded retinal information into rate-coded turning commands in the reticulospinal
      neurons via a recruitment network mimicking the layered structure of tectal
      areas. Via engagement of the basal ganglia, the system proves to be capable of
      selecting among several possible responses, even if exposed to conflicting
      stimuli. The anatomically based structure of the control system makes it possible
      to disconnect different neural components, yielding concrete predictions of how
      animals with corresponding lesions would behave. The model confirms that the
      neural networks identified in the lamprey are capable of responding appropriately
      to simple, multiple, and conflicting stimuli. 

PMID- 23124919
TI  - Dynamic primitives of motor behavior.
AB  - We present in outline a theory of sensorimotor control based on dynamic
      primitives, which we define as attractors. To account for the broad class of
      human interactive behaviors-especially tool use-we propose three distinct
      primitives: submovements, oscillations, and mechanical impedances, the latter
      necessary for interaction with objects. Owing to the fundamental features of the
      neuromuscular system-most notably, its slow response-we argue that encoding in
      terms of parameterized primitives may be an essential simplification required for
      learning, performance, and retention of complex skills. Primitives may
      simultaneously and sequentially be combined to produce observable forces and
      motions. This may be achieved by defining a virtual trajectory composed of
      submovements and/or oscillations interacting with impedances. Identifying
      primitives requires care: in principle, overlapping submovements would be
      sufficient to compose all observed movements but biological evidence shows that
      oscillations are a distinct primitive. Conversely, we suggest that kinematic
      synergies, frequently discussed as primitives of complex actions, may be an
      emergent consequence of neuromuscular impedance. To illustrate how these dynamic
      primitives may account for complex actions, we briefly review three types of
      interactive behaviors: constrained motion, impact tasks, and manipulation of
      dynamic objects.

PMID- 23124920
TI  - Germ line specific expression of a vasa homologue gene in turbot (Scophthalmus
      maximus): evidence for vasa localization at cleavage furrows in euteleostei.
AB  - Specification of primordial germ cells during early embryogenesis is a critical
      biological issue in reproduction and development. Yet, little is known in marine
      economic fish species. Vasa, a component of germ plasm, is the most-documented
      germ cell marker in teleosts. We isolated a full-length vasa cDNA (Smvas) from
      turbot (Scophthalmus maximus), a marine Euteleostei species, and investigated its
      expression patterns by RT-PCR and in situ hybridization during embryogenesis and
      gametogenesis to identify the germ cell lineage in this species. The deduced
      amino acid sequence of the isolated cDNA shared typical characteristics of Vasa
      protein and high identity to Vasa homologues in medaka (76.9%) and zebrafish
      (68.5%). The Smvas transcripts were exclusively detected in germ cells of testis
      and ovary, and exhibited an interesting dynamic localization pattern during
      oogenesis. The distribution pattern of Smvas during embyogenesis in this
      Euteleostei closely resembled the pattern observed in zebrafish (belonging to
      Osteriophysans) rather than medaka (belonging to Euteleostei). Thus, it is
      concluded that Smvas isolated in this study is a germ cell specific molecular
      marker in turbot. Furthermore, we hypothesize that Euteleostei could localize
      vasa mRNA by a special mode. The results not only facilitate the germ cell
      manipulation of the turbot, but also improve our understanding of germline
      development and evolution of vasa localization in teleost.

PMID- 23124921
TI  - Oxidative stress: a systemic factor implicated in the pathogenesis of hepatic
      encephalopathy.
AB  - Although ammonia is considered the main factor involved in the pathogenesis of
      hepatic encephalopathy (HE), it correlates well with the severity of HE in acute
      liver failure, but not in chronic liver disease. Oxidative stress is another
      factor believed to play a role in the pathogenesis of this syndrome; it
      represents an imbalance between the production and neutralization of reactive
      oxygen species, which leads to cellular dysfunction. In the setting of liver
      disease, oxidative stress represents a systemic phenomenon induced by several
      mechanisms: decreased antioxidant synthesis, increased systemic release of
      oxidant enzymes, generation of reactive oxygen species, and impaired neutrophil
      function. High ammonia concentrations induce cerebral oxidative stress, thus
      contributing to severe hepatic encephalopathy, as observed in acute liver
      failure. In chronic liver disease, significantly lower degrees of hyperammonemia
      (<500 MUM) do not induce cerebral nor systemic oxidative stress. Data from both
      animal and human studies sustain that there is a synergistic effect between
      systemic oxidative stress, and ammonia that is implicated in the pathogenesis of
      hepatic encephalopathy.

PMID- 23124922
TI  - Frontal silent sinus syndrome.

PMID- 23124923
TI  - Total laryngectomy: national and regional case volume trends 1998-2008.
AB  - OBJECTIVE: The management of advanced laryngeal cancer is evolving, with
      increasing use of chemoradiation as initial treatment. Recent reports confirm a
      decline in total laryngectomies (TLs) in the United States. A study was
      undertaken to evaluate national and regional trends in TLs performed over the
      most recent decade for which data were available and to use multivariate analysis
      to characterize these trends in more detail. STUDY DESIGN: Population-based
      cohort study. SETTING: Healthcare Cost and Utilization Project-Nationwide
      Inpatient Sample from 1998 to 2008. SUBJECTS AND METHODS: All patients underwent
      radical or complete laryngectomy. Descriptive statistics and linear and
      multivariate regressions were performed on both raw case volumes and nationally
      extrapolated figures. RESULTS: In this nationally representative sample, 8288 TL
      cases met inclusion criteria between 1998 and 2008. The TL case volumes decreased
      by 27.3 per year (P = .005) and showed increasing trends in high-volume centers.
      The number of hospitals performing TLs decreased by 12.3 per year (P < .0005).
      The South and Midwest showed higher case volumes even after controlling for
      multiple covariates. CONCLUSION: Total laryngectomy cases are decreasing and
      concentrating into high-volume centers. This study demonstrated unexplained
      regional variation in case volumes. These findings may affect patients,
      otolaryngology residency training, surgeons, and reimbursement.

PMID- 23124924
TI  - Adult recurrent respirator papillomatosis: a new therapeutic approach with
      pegylated interferon alpha 2a (Peg-IFNalpha-2a) and GM-CSF.
AB  - OBJECTIVE: To determine a new therapeutic approach using granulocyte monocyte
      colony-stimulating factor (GM-CSF) and pegylated interferon alpha 2a (Peg
      IFNalpha-2a) as adjuvant therapy in patients with adult recurrent respiratory
      papillomatosis. STUDY DESIGN: Descriptive observational clinical trial. SETTING:
      Departments of Otolaryngology and Immunology. METHODS: Fourteen patients with
      adult recurrent respiratory papillomatosis were examined regarding medical
      history and number of operations before and after treatment. Voice disorder and
      glottal stop were evaluated using the Voice-Related Quality-of-Life instrument.
      Papilloma staging was determined using the Coltera/Derkay diagram. The patients
      received Peg-IFNalpha-2a at 180 mcg weekly for 6 months. In the third month, the
      patients began GM-CSF treatment at 400 mcg weekly for 2 months. The patients were
      observed for 12 months after treatment ended. RESULTS: Eleven patients met the
      study criteria; 3 patients had tracheotomies before treatment, and they were
      decannulated after treatment. Before treatment, the scale of voice quality ranged
      from 34 to 45 points (mean, 38.31). After treatment, the range was 12 to 35
      points (mean, 21.09; P < .001). Prior to therapy, the glottal stop ranged from
      50% to 90% (average, 62.27%). After therapy, the range decreased to 0% to 15%
      (mean, 4.63%; P < .001). The number of surgical interventions decreased. Two
      patients each had 1 surgical intervention after treatment began. CONCLUSION: A
      new adjuvant treatment based on immunogenetic mechanisms against human laryngeal
      papilloma virus, with expectations of reducing disease aggressiveness and the
      number of operations, avoids the risks of surgery. IMPLICATION FOR PRACTICE: Peg
      IFNalpha-2a and GM-CSF is an adjuvant therapy for treating adult recurrent
      respiratory papillomatosis.

PMID- 23124925
TI  - The importance of the number of reflux episodes in the diagnosis of
      laryngopharyngeal reflux disease.
AB  - OBJECTIVE: The aim of this study is to evaluate the sensitivity parameters of the
      percentage of time the pH is <4 and >7, as well as the total number of
      laryngopharyngeal reflux episodes in 24 hours, in patients with suspected
      laryngopharyngeal reflux disease. STUDY DESIGN: Retrospective controlled study.
      SETTING: University hospital. SUBJECTS AND METHODS: The study was conducted on 46
      patients with laryngopharyngeal reflux disease and 58 healthy controls. Patients
      and controls underwent 24 hours of dual-probe pH monitoring of the distal and
      cervical esophagus. Patients completed a Reflux Symptom Index questionnaire and
      underwent esophageal manometry. Data concerning the percentage of time the pH was
      <4 and >7 and the number of reflux episodes registered at the cervical esophagus
      were collected and evaluated. RESULTS: The percentage of time the pH is <4 and
      the number of laryngopharyngeal reflux episodes seem to be a reliable diagnostic
      laryngopharyngeal reflux criterion reaching satisfactory sensitivity (81% and
      83%, respectively). Although the pH >7 parameter appeared statistically different
      between the 2 groups (P < .001), the sensitivity of the test appeared to be poor
      (55%). CONCLUSION: Our study demonstrates the importance of the absolute number
      of laryngopharyngeal reflux episodes in 24 hours in the diagnosis of patients
      with suspected laryngopharyngeal reflux, proposing it as a new diagnostic
      criterion.

PMID- 23124926
TI  - The anthocyanin metabolites gallic acid, 3-O-methylgallic acid, and 2,4,6
      trihydroxybenzaldehyde decrease human colon cancer cell viability by regulating
      pro-oncogenic signals.
AB  - Anthocyanins are a class of polyphenols abundant in the skins of red grapes, and
      have been shown to have anti-cancer effects in models of colon cancer [Cooke et
      al. Int J Cancer 2006;119:2213-2220; Jing et al. J Agric Food Chem 2008;56:9391
      9398]. Gut microflora metabolize anthocyanins to phenolic acids and aldehydes.
      These metabolites may explain the relationship between anthocyanin consumption
      and reduced incidence of colorectal cancer (CRC). Previously, gallic acid (Gal),
      3-O-methylgallic acid (Megal), and 2,4,6-trihydroxybenzaldehyde (THBA) were found
      to decrease Caco-2 cell viability to a larger extent than other anthocyanin
      metabolites. To better understand the potential anti-CRC action of these
      compounds, this paper investigated their capacity to modulate the cell cycle, and
      induce apoptotic cell death. Dividing Caco-2 cells were incubated for 24-72 h in
      the presence of 10-100 uM Gal, Megal, THBA, and malvidin-3-glucoside (M3g). THBA
      reduced cell viability only at 100 uM, while Gal and Megal (10-100 uM) caused a
      time- and dose-dependent decrease in cell viability. After 72 h incubation, the
      metabolites caused cell cycle arrest at G0 /G1 . The activation of the apoptotic
      pathway by Megal, Gal, and THBA was evidenced by the activation of caspase-3.
      However, only Megal and Gal caused DNA fragmentation and nuclear condensation.
      Megal, Gal, and THBA inhibited transcription factors NF-kappaB, AP-1, STAT-1, and
      OCT-1 which are known to be activated in CRC. In conclusion, the anti-cancer
      effects of Megal and Gal occurs as a consequence of both the inhibition of cell
      proliferation and induction of apoptosis. The inhibition of transcription factors
      that promote cell proliferation and survival can in part underlie the observed
      effects.

PMID- 23124928
TI  - Friedel-Crafts arylation for the formation of C(sp2)-C(sp2) bonds: a route to
      unsymmetrical and functionalized polycyclic aromatic hydrocarbons from aryl
      triazenes.

PMID- 23124927
TI  - Expression of free HLA class I heavy chains in an immune-privileged site: comment
      on the article by Taurog et al.

PMID- 23124929
TI  - Eu3+-activated Y2MoO6: a narrow band red-emitting phosphor with strong near-UV
      absorption.
AB  - Near-UV excited narrow line red-emitting phosphors, Eu(3+)-activated Y2MoO6
      systems, were synthesized using a simple molten salt reaction. The structure and
      photoluminescence characteristics were investigated using X-ray powder
      diffraction, UV-Vis absorption and fluorescent spectrophotometry. The excitation
      spectra show strong broad-band absorptions in the near-UV to blue light regions
      which match the radiation of near-UV light-emitting diode chips well. Under
      excitation of either near-UV or blue light, intense red emission with a main peak
      of 611 nm is observed, ascribed to the (5)D0-(7)F2 transition of Eu(3+) ions; the
      optimal doping concentration is 20 mol%. The chromaticity coordinates (x = 0.65,
      y = 0.34) of the as-obtained phosphor are very close to the National Television
      Standard Committee standard values (x = 0.67, y = 0.33). All these
      characteristics suggest that this material is a promising red-emitting phosphor
      candidate for white-LEDs based on near-UV LED chips.

PMID- 23124930
TI  - Immediate and long-term results following balloon mitral valvotomy in patients
      with atrial fibrillation.
AB  - BACKGROUND: The purpose of this study was to examine the influence of atrial
      fibrillation (AF) on the immediate and long-term outcome of patients undergoing
      balloon mitral valvotomy (BMV). HYPOTHESIS: Patients with atrial fibrillation
      fair poorly after balloon mitral valvotomy. METHODS: There were a total of 818
      consecutive patients who underwent elective BMV in this institute from 1997 to
      2003, with either double-lumen or triple-lumen BMV catheters included in the
      study. Of them, 95 were with AF. The clinical, echocardiographic, and hemodynamic
      data of these patients were compared with those of 723 patients in normal sinus
      rhythm (NSR). Immediate procedural results and long-term events were compared
      between the 2 study groups. RESULTS: Patients with AF were older (39.9 +/- 9.9
      years vs 29.4 +/- 10.1, P < 0.001) and presented more frequently with New York
      Heart Association (NYHA) class III-IV (53.7% vs 32.9%, P < 0.001),
      echocardiographic score >8 (47.4% vs 24.9%, P < 0.001), and with history of
      previous surgical commissurotomy (33.7% vs 11.5%, P < 0.001). In patients with
      AF, BMV resulted in inferior immediate and long-term outcomes, as reflected in a
      lesser post-BMV mitral valve area (1.3 +/- 0.4 vs 1.6 +/- 0.4 cm(2), P = 0.032)
      and higher event rate on follow-up. CONCLUSIONS: Patients with AF were older,
      sicker, and had advanced rheumatic mitral valve disease. They had a higher
      incidence of stroke, new onset heart failure, and need for reinterventions on
      long-term follow-up. These patients need intense and more frequent follow-up.

PMID- 23124931
TI  - Anatomical distribution of sex steroid hormone receptors in the brain of female
      medaka.
AB  - Estrogen and androgen play crucial roles in coordinating reproductive functions
      through estrogen receptors (ERs) and androgen receptors (ARs), respectively.
      These receptors are considered important for regulation of the hypothalamo
      pituitary-gonadal (HPG) axis. Despite their biological importance, the
      distribution of sex steroid receptors has not been fully analyzed anatomically in
      the teleost brain. The teleosts have many characteristic features, which allow
      unique approaches toward an understanding of the regulatory mechanisms of
      reproductive functions. Medaka serves as a good model system for studying the
      mechanisms by which steroid receptor-mediated systems are regulated, because (1)
      their breeding conditions can be easily manipulated; (2) we can take advantage of
      the genome database; and 3) molecular genetic tools, such as transgenic
      techniques, are applicable. We analyzed the distribution of ERalpha, ERbeta1,
      ERbeta2, ARalpha, and ARbeta mRNA by in situ hybridization in the brain of female
      medaka. We found that all subtypes of ERs and ARs were expressed in the following
      nuclei: the dorsal part of the ventral telencephalic area (Vd), supracommissural
      part of the ventral telencephalic area (Vs), postcommissural part of the ventral
      telencephalic area (Vp), preoptic area (POA), and nucleus ventralis tuberis
      (NVT). These regions are known to be involved in the regulation of sexual
      behavior (Vd, Vs, Vp, POA) or the HPG axis (NVT). These ER- and/or AR-expressing
      neurons may regulate sexual behavior or the HPG axis according to their axonal
      projections. Future analysis should be targeted to the neurons described in the
      present study to extend our understanding of the central regulatory mechanisms of
      reproduction.

PMID- 23124932
TI  - Validation of a coding algorithm to identify patients with hepatocellular
      carcinoma in an administrative database.
AB  - PURPOSE: International Classification of Disease, Ninth Revision, Clinical
      Modification (ICD-9-CM)-based algorithms to identify patients with hepatocellular
      carcinoma (HCC) have not been developed outside of the Veterans Affairs
      healthcare setting. The development and validation of such algorithms are
      necessary for the conduct of population-based studies evaluating the epidemiology
      and comparative effectiveness and safety of therapies for HCC. METHODS: We
      queried electronic medical records at two tertiary care hospitals to identify
      patients with two ICD-9-CM diagnosis codes for a chronic liver disease and/or
      cirrhosis plus two ICD-9-CM codes for HCC. We determined the positive predictive
      value (PPV) of this algorithm by comparing it to diagnoses of HCC confirmed by
      expert medical record review. RESULTS: Among 101 patients meeting the algorithm,
      88 (PPV: 87.1%; 95% CI: 79.0-93.0%) had confirmed HCC. The algorithm's
      sensitivity was 91.7% among patients with confirmed HCC, and its specificity was
      98.7% among chronic liver disease patients without HCC. Excluding patients who
      received systemic chemotherapy in the 12 months prior to or 6 months after the
      initial ICD-9-CM code in the algorithm, the PPV increased to 91.6% (87/95; 95%
      CI: 84.1-96.3%). CONCLUSIONS: The presence of at least two ICD-9-CM codes for a
      chronic liver disease and/or cirrhosis plus two ICD-9-CM codes for HCC has a high
      PPV for identifying HCC cases. This simple, claims-based algorithm can be used in
      future epidemiologic studies to examine risk factors for HCC and evaluate
      outcomes and adverse events of medical therapies prescribed for HCC patients.

PMID- 23124933
TI  - Cardiac tamponade due to rupture of coronary artery fistula to the coronary sinus
      with giant aneurysm of coronary artery: usefulness of transthoracic
      echocardiography.
AB  - A 68-year-old woman was admitted to our hospital because of back pain and
      syncope. Transthoracic echocardiography revealed pericardial effusion, a
      collapsed right ventricle, a giant aneurysm connected to the coronary sinus, a
      dilated left main trunk coronary artery, and a dilated left circumflex artery
      (LCx). Furthermore, there was a coronary artery fistula arising from the LCx that
      drained into the coronary sinus. We diagnosed cardiac tamponade due to rupture of
      the coronary artery fistula or giant aneurysm, and successful emergency surgery
      was performed. Rupture of coronary artery aneurysm or coronary artery fistula is
      very rare. Transthoracic two-dimensional echocardiography was very useful in our
      case for the diagnosis of cardiac tamponade, giant coronary aneurysm, and
      coronary artery fistula. 

PMID- 23124934
TI  - Rhodium-catalyzed enantioselective nucleophilic fluorination: ring opening of
      oxabicyclic alkenes.

PMID- 23124936
TI  - Nanotechnology-enabled energy harvesting for self-powered micro-/nanosystems.
AB  - Health, infrastructure, and environmental monitoring as well as networking and
      defense technologies are only some of the potential areas of application of micro
      /nanosystems (MNSs). It is highly desirable that these MNSs operate without an
      external electricity source and instead draw the energy they require from the
      environment in which they are used. This Review covers various approaches for
      energy harvesting to meet the future demand for self-powered MNSs.

PMID- 23124937
TI  - Competency frameworks: universal or local.

PMID- 23124938
TI  - Overview of influenza viruses.
AB  - The influenza virus (IV) is still of great importance as it poses an immanent
      threat to humans and animals. Among the three IV-types (A, B, and C) influenza A
      viruses are clinically the most important being responsible for severe epidemics
      in humans and domestic animals. Aerosol droplets transmit the virus that causes a
      respiratory disease in humans that can lead to severe pneumonia and ultimately
      death. The high mutation rate combined with the high replication rate allows the
      virus to rapidly adapt to changes in the environment. Thereby, IV escape the
      existing immunity and become resistant to drugs targeting the virus. This causes
      annual epidemics and demands for new compositions of the yearly vaccines.
      Furthermore, due to the nature of their segmented genome, IV can recombine
      segments. This can eventually lead to the generation of a virus with the ability
      to replicate in humans and with novel antigenic properties that can be the cause
      of a pandemic outbreak. For its propagation the virus binds to the target cells
      and enters the cell to replicate its genome. Newly produced viral proteins and
      genomes are packaged at the cell membrane where progeny virions are released. As
      all viruses IV depends on cellular functions and factors for their own
      propagation, and therefore intensively interact with the cells. This dependency
      opens new possibilities for anti-viral strategies.

PMID- 23124935
TI  - Rituximab in the treatment of refractory adult and juvenile dermatomyositis and
      adult polymyositis: a randomized, placebo-phase trial.
AB  - OBJECTIVE: To assess the safety and efficacy of rituximab in a randomized, double
      blind, placebo-phase trial in adult and pediatric myositis patients. METHODS:
      Adults with refractory polymyositis (PM) and adults and children with refractory
      dermatomyositis (DM) were enrolled. Entry criteria included muscle weakness and
      >=2 additional abnormal values on core set measures (CSMs) for adults. Juvenile
      DM patients required >=3 abnormal CSMs, with or without muscle weakness. Patients
      were randomized to receive either rituximab early or rituximab late, and
      glucocorticoid or immunosuppressive therapy was allowed at study entry. The
      primary end point compared the time to achieve the International Myositis
      Assessment and Clinical Studies Group preliminary definition of improvement (DOI)
      between the 2 groups. The secondary end points were the time to achieve >=20%
      improvement in muscle strength and the proportions of patients in the early and
      late rituximab groups achieving the DOI at week 8. RESULTS: Among 200 randomized
      patients (76 with PM, 76 with DM, and 48 with juvenile DM), 195 showed no
      difference in the time to achieving the DOI between the rituximab late (n = 102)
      and rituximab early (n = 93) groups (P = 0.74 by log rank test), with a median
      time to achieving a DOI of 20.2 weeks and 20.0 weeks, respectively. The secondary
      end points also did not significantly differ between the 2 treatment groups.
      However, 161 (83%) of the randomized patients met the DOI, and individual CSMs
      improved in both groups throughout the 44-week trial. CONCLUSION: Although there
      were no significant differences in the 2 treatment arms for the primary and
      secondary end points, 83% of adult and juvenile myositis patients with refractory
      disease met the DOI. The role of B cell-depleting therapies in myositis warrants
      further study, with consideration for a different trial design.

PMID- 23124939
TI  - One health from a social-ecological systems perspective: enriching social and
      cultural dimensions.
AB  - This chapter offers insights from the environmental management paradigm of
      'social-ecological systems' and related bodies of theory on people-environment
      relationships to assist the evolution of the One Health interdisciplinary
      endeavour of health promotion across human-animal ecosystem relationships. It
      also seeks to expand thinking about the social and cultural dimensions that are
      likely to prove important in the development of thinking and practice in the One
      Health field. It advocates consideration of cultural and economic relationships
      affecting people's interactions with domesticated and wild animal species and
      ecosystems, and exploration of the cognitive and behavioural aspects of these
      interactions. 

PMID- 23124942
TI  - Treatment of inherited homocystinurias.
AB  - Inherited homocystinurias, have in common, accumulation of homocysteine with
      subsequent neurotoxicity; they also encompass two distinctive clinical entities:
      classical homocystinuria due to cystathionine beta-synthase (CBS) deficiency and
      the rare inborn errors of cobalamin and folate metabolism. In the latter group,
      remethylation disorders of homocysteine to methionine (chiefly CblC defect and
      5,10-methylenetetrahydrofolate reductase [MTHFR] deficiency) are by far the most
      frequently encountered situations. The natural history of CBS deficiency is
      relatively well known and described. Similarly, clinical presentations of
      remethylation defects are becoming better recognized and reported. Conversely,
      few data are available regarding treatment of these disorders, especially for
      remethylation defects. In this review, after an overview of the metabolic
      pathophysiology and the clinical features of inherited homocystinurias due to CBS
      deficiency, CblC defect, and MTHFR deficiency, we focus on present and
      prospective therapeutic approaches.

PMID- 23124940
TI  - Cardiac metabolism in hypertrophy and heart failure: implications for therapy.
AB  - The heart consumes huge amounts of energy to fulfil its function as a relentless
      pump. A highly sophisticated system of energy generation based on flexibility of
      substrate use and efficient energy production, effective energy sensing and
      energy transfer ensures function of the healthy heart across a range of
      physiological situations. In left ventricular hypertrophy and heart failure,
      these processes become disturbed, leading as will be discussed to impaired
      cardiac energetic status and to further impairment of cardiac function. These
      metabolic disturbances form a potential target for therapy. 

PMID- 23124941
TI  - Fibrosis and heart failure.
AB  - The extracellular matrix (ECM) is a living network of proteins that maintains the
      structural integrity of the myocardium and allows the transmission of electrical
      and mechanical forces between the myocytes for systole and diastole. During
      ventricular remodeling, as a result of iterations in the hemodynamic workload,
      collagen, the main component of the ECM, increases and occupies the areas between
      the myocytes and the vessels. The resultant fibrosis (reparative fibrosis) is
      initially a compensatory mechanism and may progress adversely influencing tissue
      stiffness and ventricular function. Replacement fibrosis appears at sites of
      previous cardiomyocyte necrosis to preserve the structural integrity of the
      myocardium, but with the subsequent formation of scar tissue and widespread
      distribution, it has adverse functional consequences. Continued accumulation of
      collagen impairs diastolic function and compromises systolic mechanics.
      Nevertheless, the development of fibrosis is a dynamic process wherein
      myofibroblasts, the principal cellular elements of fibrosis, are not only
      metabolically active and capable of the production and upregulation of cytokines
      but also have contractile properties. During the process of reverse remodeling
      with left ventricular assist device unloading, cellular, structural, and
      functional improvements are observed in terminal heart failure patients. With the
      advent of anti-fibrotic pharmacologic therapies, cellular therapy, and
      ventricular support devices, fibrosis has become an important therapeutic target
      in heart failure patients. Herein, we review the current concepts of fibrosis as
      a main component of ventricular remodeling in heart failure patients. Our aim is
      to integrate the histopathologic process of fibrosis with the neurohormonal,
      cytochemical, and molecular changes that lead to ventricular remodeling and its
      physiologic consequences in patients. The concept of fibrosis as living scar
      allows us to envision targeting this scar as a means of improving ventricular
      function in heart failure patients. 

PMID- 23124944
TI  - Presence of adrenergic receptors in rat endolymphatic sac epithelial cells.
AB  - Intravenous application of catecholamines produces a depression in the
      endolymphatic sac direct current potential (ESP) and increases endolymphatic
      pressure via the beta-adrenergic receptor (AR) in guinea pigs, suggesting that
      catecholamines play a role in the endolymphatic system. However, the localization
      of ARs in the endolymphatic sac (ES) is still undetermined. The presence of ARs
      in the rat ES was investigated by reverse transcriptase-polymerase chain reaction
      using laser capture microdissection (LCM) and immunohistochemical analysis.
      Expression of alpha(1A)-, alpha(1B)-, alpha(2A)-, alpha(2B)-, beta(1)-, beta(2)-
      and beta(3)-ARs was observed in LCM samples of ES epithelia. Immunohistochemical
      analysis using specific antibodies showed immunofluorescence of beta(2)- and
      beta(3)-ARs in epithelial cells of the ES intermediate portion, and no specific
      staining results were obtained for alpha(1)-, alpha(2A)-, alpha(2B)- and beta(1)
      ARs. The presence of beta(2)-AR with no clear immunostaining of beta(1)-AR in ES
      epithelial cells is in accordance with previous electrophysiological and
      pharmacological results, which suggests that beta(2)-AR mediates the action of
      catecholamines on the ESP. The presence of beta(3)-AR in the ES epithelial cells
      and its absence in the stria vascularis implies that beta(3)-AR plays a specific
      role in the ES.

PMID- 23124946
TI  - C-terminal membrane association of Bestrophin 3 and its activation as a chloride
      channel.
AB  - Bestrophin 3 (Best3), a member of the bestrophin Cl(-) channel family, is a
      candidate of cGMP-sensitive, Ca(2+)-activated Cl(-) channel in vascular smooth
      muscle cells. The Best3 channel was recently found to play an important role in
      vasomotion. However, the mechanism for its activation has not been clarified. In
      previous studies, we found that a Best3 C-terminal sequence (amino acids 353-404)
      was associated with the cellular membrane. The sequence includes an
      autoinhibitory domain ((356)IPSFLGS(362)) and a downstream basic residue domain
      (amino acids 384-397). In this study, we found that the sequence (368-383)
      between the two domains is actually a determinant for Best3 C-terminal membrane
      associability. Deletion of the sequence almost abolished the membrane association
      but did not activate the Best3 channel. Treatment of Best3-expressing HEK293
      cells with the PI3Kalpha inhibitor IV (a Best3 activator) could not abolish but
      weakened the Best3 membrane association. The result supports the assumption that
      the positively charged basic residues in the Best3 C terminus are likely
      associated with the membranous negatively charged phospholipids, which plays a
      role in the regulation of Best3 activation. But the relationship between membrane
      associability and Best3 activation seems more complicated than expected.

PMID- 23124945
TI  - Susceptibility test of two Ca(2+)-ATPase conformers to denaturants and polyols to
      outline their structural difference.
AB  - To determine the effect of denaturants [guanidine hydrochloride (GdnHCl) and
      urea] and polyols [with various molecular masses (62.1-600)] on calcium binding
      at the two hypothesized conformers (A and B forms) of the chemically equivalent
      sarcoplasmic reticulum Ca(2+)-ATPase, which bind two calcium ions in different
      manners, we examined the effect of these reagents on the calcium dependence of
      ATP-supported phosphorylation of the ATPase molecules and of their calcium
      activated, acetyl phosphatate hydrolytic activity. (1) GdnHCl (~0.05 M) and urea
      (~0.5 M) increased the apparent calcium affinity (K (0.5)) of 2-6 MUM of
      noncooperative binding [Hill coefficient (n (H)) ~ 1] of the A form to 10-40 MUM.
      (2) The employed polyols transformed the binding of the A form into cooperative
      binding (n (H) ~ 2), accompanying the approach of its K (0.5) value to that (K
      (0.5) = 0.04-0.2 MUM) of the cooperative binding (n (H) ~ 2) of the B form; the
      transition concentration (0.025-2 M) of the polyols, above which such
      transformation occurs, was in inverse relation to their molecular mass. (3) The
      binding of the B form was resistant to these denaturants and polyols. Based on
      these data, a structural model of the two forms, calcium-binding domains of which
      are loosely and compactly folded, is presented.

PMID- 23124947
TI  - Environmental regulation of mitochondria-rich cells in Chalcalburnus tarichi
      (Pallas, 1811) during reproductive migration.
AB  - Chalcalburnus tarichi is an anadromous cyprinid fish that has adapted to extreme
      conditions (salinity 22 0/00, pH 9.8 and alkalinity 153 mEq * l-1) in Lake Van in
      eastern Turkey. Changes in immunoreactivity of Na+/K+-ATPase in gill tissue and
      osmolarity and ion levels in plasma were investigated in C. tarichi during
      reproductive migration. Physicochemical characteristics and ion levels in Lake
      Van were high compared freshwater. Plasma osmolality and plasma ion
      concentrations ([Na+], [K+] and [Cl-]) increased after transfer from freshwater
      to Lake Van. The mitochondria-rich (MR) cells of the gill were stained in both
      filament and lamellar epithelia of C. tarichi by immunocytochemistry with a
      specific antiserum for Na+/K+-ATPase in river fish samples. Density and area of
      MR cells were decreased in lake-adapted fishes. These results indicated that
      freshwater acclimation capacity is correlated with the size and distribution of
      MR cells in C. tarichi, in contrast to many teleost fishes.

PMID- 23124948
TI  - Retraction. ATP consumption by sarcoplasmic reticulum Ca2+ pumps accounts for 50%
      of resting metabolic rate in mouse fast and slow twitch skeletal muscle. Am J
      Physiol Cell Physiol. 2010 Mar;298(3):C521-9. doi: 10.1152/ajpcell.00479.2009.

PMID- 23124950
TI  - Transparent nanowire network electrode for textured semiconductors.
AB  - This work presents an inexpensive and easily manufacturable, highly conductive
      and transparent nanowire network electrode for textured semiconductors. It is
      based on lines of silver nanoparticles transformed into a nanowire network by
      microwave or furnace sintering. The nanonetwork electrode on crystalline silicon
      is demonstrated experimentally, with the nanoparticles self-assembling in the
      valleys between the pyramids of the textured surface. Optical experiments show
      that this conductive nanowire network electrode can be essentially 'invisible'
      when covered with the conventional anti-reflection coating (ARC), and thus could
      be employed in photovoltaic applications.

PMID- 23124951
TI  - Synthesis, pharmacological evaluation and conformational investigation of
      endomorphin-2 hybrid analogues.
AB  - This study reports on new pharmacologically active endomorphin-2 analogues,
      incorporating beta(2)-hPhe, beta(3)-hPhe and beta(3)-hTic unnatural amino acids
      in the place of the Phe(3)-Phe(4)residues. Such alpha, beta-hybrid analogues were
      designed to exploit the great potential of beta-amino acids in generating
      conformational variation at the key positions 3 and 4, with the aim of evaluating
      the effect on the opioid binding affinity. Ligand-stimulated binding assays
      indicated that some analogues retained a significant affinity, especially for the
      delta receptor. (1)H NMR and molecular modelling suggested the predominance of
      bent structures for all compounds. The molecular docking with the MU-opioid
      receptor model was also performed, highlighting a common binding mode for active
      compounds and helping to rationalize the observed structure-activity data.

PMID- 23124952
TI  - Using self-organizing map (SOM) and support vector machine (SVM) for
      classification of selectivity of ACAT inhibitors.
AB  - Using a self-organizing map (SOM) and support vector machine, two classification
      models were built to predict whether a compound is a selective inhibitor toward
      the two Acyl-coenzyme A: cholesterol acyltransferase (ACAT) isozymes, ACAT-1 and
      ACAT-2. A dataset of 97 ACAT inhibitors was collected. For each molecule, the
      global descriptors, 2D and 3D property autocorrelation descriptors and
      autocorrelation of surface properties were calculated from the program
      ADRIANA.Code. The prediction accuracies of the models (based on the training/
      test set splitting by SOM method) for the test sets are 88.9 % for SOM1, 92.6 %
      for SVM1 model. In addition, the extended connectivity fingerprints (ECFP_4) for
      all the molecules were calculated and the structure-activity relationship of
      selective ACAT inhibitors was summarized, which may help find important
      structural features of inhibitors relating to the selectivity of ACAT isozymes.

PMID- 23124953
TI  - Renal denervation: a potential new treatment for severe hypertension.
AB  - Hypertension is a leading cause of cardiovascular morbidity and mortality. Drug
      resistant hypertension remains common despite the availability of several classes
      of effective antihypertensive agents. Sympathetic hyperactivity has long been
      recognized as a major contributor to resistant hypertension, but radical
      sympathectomy was abandoned several decades ago due to its significant side
      effects. The newly developed, minimally invasive, catheter-based renal
      sympathetic denervation procedure has been shown in recent trials to produce
      impressive blood pressure reductions and a favorable safety profile in drug
      resistant hypertension. Although the long-term efficacy and safety of renal
      denervation remains to be determined, emerging data suggest that the benefits of
      renal denervation may extend beyond blood pressure control.

PMID- 23124954
TI  - Trans-platinum/thiazole complex interferes with Sp1 zinc-finger protein.

PMID- 23124957
TI  - Transgenic labeling of higher order neuronal circuits linked to phospholipase C
      beta2-expressing taste bud cells in medaka fish.
AB  - The sense of taste plays a pivotal role in the food-selecting behaviors of
      vertebrates. We have shown that the fish ortholog of the phospholipase C gene
      (plc-beta2) is expressed in a subpopulation of taste bud cells that transmit
      taste stimuli to the central nervous system to evoke favorable and aversive
      behaviors. We generated transgenic medaka expressing wheat germ agglutinin (WGA)
      under the control of a regulatory region of the medaka plc-beta2 gene to analyze
      the neuronal circuit connected to these sensory cells. Immunohistochemical
      analysis of the transgenic fish 12 days post fertilization revealed that the WGA
      protein was transferred to cranial sensory ganglia and several nuclei in the
      hindbrain. WGA signals were also detected in the secondary gustatory nucleus in
      the hindbrain of 3-month-old transgenic fish. WGA signals were observed in
      several diencephalic and telencephalic regions in 9-month-old transgenic fish.
      The age-dependent increase in the labeled brain regions strongly suggests that
      labeling occurred at taste bud cells and progressively extended to cranial nerves
      and neurons in the central nervous system. These data are the first to
      demonstrate the tracing of higher order gustatory neuronal circuitry that is
      associated with a specific subpopulation of taste bud cells. These results
      provide insight into the basic neuronal architecture of gustatory information
      processing that is common among vertebrates.

PMID- 23124958
TI  - Identifying periods of acceptable computer usage in primary care research
      databases.
AB  - PURPOSE: To examine the effect of applying different data quality filters on the
      incidence of disease and prescribing trends over time in a primary care research
      database and validate a new method for defining periods of adequate computer
      usage. METHODS: Acceptable computer usage (ACU) was defined as the year in which
      a general practice was continuously entering on average at least two therapy
      records, one medical record and one additional health data record per patient per
      year. The effect of using this date on the incidence of a range of outcomes
      (antibiotic prescriptions, myocardial infarction, colon cancer, lung cancer) over
      time was compared with other methods for defining the start of patient follow-up
      in The Health Improvement Network (THIN) primary care database containing UK
      patient records. Various combinations of the follow-up start dates were applied
      to the data to calculate incidence rates: (i) registration date, (ii) practice
      computerization date, (iii) acceptable mortality recording (AMR) (iv) ACU.
      RESULTS: On average, the ACU date was 3.3 years after the AMR date. Applying the
      AMR or ACU dates separately or in combination produced trends in incidence rates
      more comparable with external data sources than using the year of practice
      registration or computerization. The estimated incidence rates were highly
      sensitive to different methods of defining start date in early time periods.
      CONCLUSIONS: Using the latest of AMR and ACU dates is useful for improving the
      integrity of THIN data.

PMID- 23124959
TI  - Reversible sensing of the anticoagulant heparin with protamine permselective
      membranes.
AB  - A permselective membrane electrode allows the rapid and operationally reversible
      detection of the polycationic polypeptide protamine in physiological samples.
      Anticoagulant levels of heparin can be measured in undiluted whole blood by
      adding a known excess of its antidote protamine to discrete blood samples.

PMID- 23124960
TI  - Temporal dynamics of microbial communities in the rhizosphere of two genetically
      modified (GM) maize hybrids in tropical agrosystems.
AB  - The use of genetically modified (GM) plants still raises concerns about their
      environmental impact. The present study aimed to evaluate the possible effects of
      GM maize, in comparison to the parental line, on the structure and abundance of
      microbial communities in the rhizosphere. Moreover, the effect of soil type was
      addressed. For this purpose, the bacterial and fungal communities associated with
      the rhizosphere of GM plants were compared by culture-independent methodologies
      to the near-isogenic parental line. Two different soils and three stages of plant
      development in two different periods of the year were included. As evidenced by
      principal components analysis (PCA) of the PCR-DGGE profiles of evaluated
      community, clear differences occurred in these rhizosphere communities between
      soils and the periods of the year that maize was cultivated. However, there were
      no discernible effects of the GM lines as compared to the parental line. For all
      microbial communities evaluated, soil type and the period of the year that the
      maize was cultivated were the main factors that influenced their structures. No
      differences were observed in the abundances of total bacteria between the
      rhizospheres of GM and parental plant lines.

PMID- 23124961
TI  - Left ventricular function in pulmonary hypertension.
AB  - To elucidate left ventricular function in pulmonary hypertension, we measured
      parameters of left ventricular as well as right ventricular function by
      echocardiography in 11 patients with pulmonary hypertension (idiopathic pulmonary
      artery hypertension in 4, chronic thromboembolic pulmonary hypertension in 5, and
      other pulmonary hypertension in 2). The percent change in these parameters 6
      months after treatment with pulmonary artery vasodilators (beraprost in 8 and
      sildenafil in 3) was assessed. There was a correlation between the relative
      change in right ventricular systolic pressure (RVSP) and the relative changes in
      left ventricular outflow tract velocity-time integral (r = -0.730, P = 0.011) and
      mitral valve velocity-time integral (r = -0.621, P = 0.041). However, there was
      no correlation between the relative change in RVSP and the relative changes in
      left ventricular ejection fraction, left ventricular diastolic dimension, and
      systolic blood pressure. The relative change in RVSP was also correlated with the
      relative change in early diastolic myocardial velocity at the medial mitral
      annulus (r = -0.675, P = 0.023). Reduction of RVSP by pulmonary artery
      vasodilators might increase left ventricular preload, leading to an increase in
      stroke volume. Right ventricular load reduction might improve left ventricular
      diastolic function in patients with pulmonary hypertension, possibly through
      altered interventricular septal performance. 

PMID- 23124962
TI  - ADAM-10 is overexpressed in rheumatoid arthritis synovial tissue and mediates
      angiogenesis.
AB  - OBJECTIVE: To examine the expression of ADAM-10 in rheumatoid arthritis (RA)
      synovial tissue (ST) and the role it plays in angiogenesis. METHODS: ADAM-10
      expression was determined using immunohistology, Western blotting, and
      quantitative polymerase chain reaction. In order to examine the role of ADAM-10
      in angiogenesis, we performed in vitro Matrigel tube formation and chemotaxis
      assays using human microvascular endothelial cells (HMVECs) transfected with
      control or ADAM-10 small interfering RNA (siRNA). To determine whether ADAM-10
      plays a role in angiogenesis in the context of RA, we performed Matrigel assays
      using a coculture system of HMVECs and RA synovial fibroblasts. RESULTS:
      Endothelial cells and lining cells within RA ST expressed high levels of ADAM-10
      compared with cells within osteoarthritis ST and normal ST. ADAM-10 expression
      was significantly elevated at the protein and messenger RNA levels in HMVECs and
      RA synovial fibroblasts stimulated with proinflammatory mediators compared with
      unstimulated cells. ADAM-10 siRNA-treated HMVECs had decreased endothelial cell
      tube formation and migration compared with control siRNA-treated HMVECs. In
      addition, ADAM-10 siRNA-treated HMVECs from the RA synovial fibroblast coculture
      system had decreased endothelial cell tube formation compared with control siRNA
      treated HMVECs. CONCLUSION: These data show that ADAM-10 is overexpressed in RA
      and suggest that ADAM-10 may play a role in RA angiogenesis. ADAM-10 may be a
      potential therapeutic target in inflammatory angiogenic diseases such as RA.

PMID- 23124963
TI  - American Society for Apheresis white paper: considerations for medical staff
      apheresis medicine physician credentialing and privileging.
AB  - INTRODUCTION: Physician supervision of apheresis contributes to safe and high
      quality patient care. Literature is limited regarding the requirements for
      hospital privileges of physicians providing apheresis services. This report
      provides recommendations from the American Society for Apheresis (ASFA) regarding
      this topic. MATERIALS AND METHODS: The ASFA Public Affairs Committee was charged
      by the society's Board of Directors (BOD) to work collaboratively with other ASFA
      committees to develop guidance pertaining to requirements for hospital privileges
      of physicians in apheresis medicine. After review of the literature and
      discussions with members from diverse practice environments, draft guidance was
      created and circulated among pertinent parties for comment and revision. The
      final document, approved by the BOD in 2011, is presented herein. RESULTS:
      Assurance of patient safety was the paramount focus in the deliberations.
      Establishment and maintenance of physician competency in the discipline of
      apheresis medicine, and the documentation thereof, were consensus priorities. The
      importance of care teams involving non-physicians and the support structures
      within hospitals were also identified as other important contributors to patient
      safety. CONCLUSION: Patient safety during therapeutic apheresis involves both
      practitioners' and institutional provision of care aspects. Physician training
      experiences, medical licensing, and board certification status, along with
      continuing medical education and participation in risk management/patient safety
      projects are characteristic facets of physician competency in the provision of
      quality apheresis medicine interventions. Documentation of such indicators may
      help in medical staff deliberations regarding physician privileging in the
      oversight and management of apheresis medicine activities in hospitals.

PMID- 23124965
TI  - Expression analysis of the polypyrimidine tract binding protein (PTBP1) and its
      paralogs PTBP2 and PTBP3 during Xenopus tropicalis embryogenesis.
AB  - The PTB (polypyrimidine tract binding protein) family of RNA-binding proteins
      plays a critical role in development through the regulation of post
      transcriptional events. We have determined expression patterns of the three
      members of this gene family ptbp1, ptbp2 and ptbp3 during Xenopus tropicalis
      embryogenesis using whole-mount in situ hybridization. Our results show that each
      paralog presents a unique pattern of expression. ptbp1 is the prevalent maternal
      mRNA and is differentially expressed in the three germ layers. Later in
      development, it is widely expressed in the embryo including the epidermis, the
      dermatome, the intermediate mesoderm, the lateral plate mesoderm and the neural
      crest. ptbp2 expression is restricted to the nervous system including the brain,
      the neural retina and the spinal cord and the intermediate mesoderm. In addition
      to being expressed in erythroid precursors, ptbp3 is present in specific
      subdomains of the brain and the spinal cord, as well as in the posterior part of
      the notochord, suggesting it may play a role in the patterning of the nervous
      system. In the eye, each of the three genes is expressed in a specific structure
      which emphasizes their non-redundant function during development. Strickingly,
      our experiments also revealed that none of the three paralogs was expressed in
      the myotome, suggesting that the absence of PTB activity is a key determinant to
      display myotomal splicing patterns.

PMID- 23124964
TI  - Calcium carbonate polyamorphism and its role in biomineralization: how many
      amorphous calcium carbonates are there?
AB  - Although the polymorphism of calcium carbonate is well known, and its polymorphs-
      calcite, aragonite, and vaterite--have been highly studied in the context of
      biomineralization, polyamorphism is a much more recently discovered phenomenon,
      and the existence of more than one amorphous phase of calcium carbonate in
      biominerals has only very recently been understood. Here we summarize what is
      known about polyamorphism in calcium carbonate as well as what is understood
      about the role of amorphous calcium carbonate in biominerals. We show that
      consideration of the amorphous forms of calcium carbonate within the physical
      notion of polyamorphism leads to new insights when it comes to the mechanisms by
      which polymorphic structures can evolve in the first place. This not only has
      implications for our understanding of biomineralization, but also of the means by
      which crystallization may be controlled in medical, pharmaceutical, and
      industrial contexts.

PMID- 23124966
TI  - Relationship between brassinosteroids and genes controlling stomatal production
      in the Arabidopsis hypocotyl.
AB  - Stomata are excellent model systems for examining the mechanisms that regulate
      cell fate determination and pattern formation. It has recently been demonstrated
      that brassinosteroids control stomatal development by regulating both the MAPK
      kinase kinase YODA and the basic helix-loop-helix transcriptional factor
      SPEECHLESS. Here, we show that these plant regulators positively regulate
      stomatal formation in the hypocotyl and also accelerate their development.
      Hormone tests, reporter gene studies and mutant analyses revealed that
      brassinosteroids act upstream of the transcriptional factors CAPRICE and GLABRA2.
      These plant regulators control an earlier stage of stomatal production than those
      regulated by the membrane receptor TOO MANY MOUTHS. This work highlights
      differences in the genetic control of stomatal development between cotyledons or
      leaves and hypocotyls.

PMID- 23124967
TI  - Loss of plakophilin 2 disrupts heart development in zebrafish.
AB  - The desmosomal armadillo protein plakophilin 2 is the only plakophilin expressed
      in the heart, and mutations in the human plakophilin 2 gene result in
      arrhythmogenic right ventricular cardiomyopathy. To investigate loss of function,
      we knocked down plakophilin 2 by morpholino microinjection in zebrafish. This
      resulted in decreased heart rate, cardiac oedema, blood pooling, a failure of the
      heart to pattern correctly and a twisted tail. Co-injection of plakophilin 2 mRNA
      rescued the morphant phenotype, indicating the specificity of the knockdown.
      Desmosome numbers were decreased in morphant hearts and the plaque and midline
      structures of the desmosomes in the intercalated discs were disrupted when
      examined by electron microscopy. cmlc2 and vmhc expression at 48 hours post
      fertilization (hpf)  showed incomplete looping of the heart in morphant embryos
      by whole mount in situ hybridization, and bmp4 expression was expanded into the
      ventricle. The domain of expression of the heart marker nkx2.5 at 24 hpf was
      expanded. At the 18 somite stage, expression of the cardiogenic gene lefty2 was
      abolished in the left cardiac field, with concomitant increases in bmp4, spaw and
      lefty1 expression, likely resulting in the looping defects. These results
      indicate that plakophilin 2 has both structural and signalling roles in zebrafish
      heart development.

PMID- 23124968
TI  - The secondary human yolk sac has an immunophenotype indicative of both hepatic
      and intestinal differentiation.
AB  - Although the microscopy of the secondary human yolk sac (SHYS) is well known, few
      studies have addressed its immunohistochemical profile. The SHYS is involved in
      the synthesis, absorption and transfer of various proteins and behaves as a
      temporary liver and intestine. The objective of this study was to evaluate the
      presence of immunohistochemical markers of hepatic and intestinal function in the
      SHYS. We performed a retrospective histological and immunohistochemical study of
      26 SHYS from spontaneous abortions and tubal pregnancies, 15 of which were from
      the 7th to 8th week. The antibodies used were against alpha-foetoprotein (AFP),
      glypican 3 (GLP3), hepatocyte-paraffin-1 (HepPar-1), villin, CDX2, SALL4 and
      podoplanin (D2-40). Early SHYS from the 5th to the 8th week revealed a network of
      intracellular vesicles communicating with the lumen of endodermal tubules that
      were highlighted by intense membrane AFP expression. Endodermal cells
      consistently expressed AFP, GLP3, SALL4, hep-par-1, villin and CDX2, while
      mesothelial cells only expressed D2-40. The endodermal layer of the SHYS from the
      5th to the 8th week revealed a transient canalicular network which was
      highlighted by strong membranous AFP expression; this may represent the substrate
      of a SHYS transport system during its period of maximal activity. The synthetic
      and transfer functions of the yolk sac endoderm were reflected in a hybrid
      immunophenotype in which proteins characteristic of hepatic function such as AFP,
      GLP3, SALL4 and hep-par-1 were coexpressed simultaneously with others such as
      villin and CDX2, indicative of an intestinal role.

PMID- 23124969
TI  - The discontinuous nature of neurofilament transport accommodates both
      establishment and repair of the axonal neurofilament array.
AB  - Neurofilaments (NFs) provide structural support to axons. Timely and regional
      deposition of NFs is essential during axonogenesis, since progressive
      stabilization of proximal axons is essential to support continued pathfinding of
      distal axonal regions. NFs undergo short bursts of microtubule-mediated axonal
      transport interspersed by prolonged pauses. We demonstrate herein that it is this
      unique "on-off" method of axonal transport, coupled with the ability of NFs to
      form cation-dependent, phosphomediated lateral associations that allow neurons to
      mediate the orderly transition from exploratory process to stabilized axon
      following synaptogenesis. We further demonstrate how this transport method
      provides for NF maintenance following maturation and encompasses the potential
      for regeneration.

PMID- 23124970
TI  - Physician response to financial incentives when choosing drugs to treat breast
      cancer.
AB  - This paper considers physician agency in choosing drugs to treat metastatic
      breast cancer, a clinical setting in which patients have few protections from
      physicians' rent seeking. Physicians have explicit financial incentives attached
      to each potential drug treatment, with profit margins ranging more than a hundred
      fold. SEER-Medicare claims and Medispan pricing data were formed into a panel of
      4,503 patients who were diagnosed with metastatic breast cancer and treated with
      anti-cancer drugs from 1992 to 2002. We analyzed the effects of product
      attributes, including profit margin, randomized controlled trial citations, FDA
      label, generic status, and other covariates on therapy choice. Instruments and
      drug fixed effects were used to control for omitted variables and possible
      measurement error associated with margin. We find that increasing physician
      margin by 10% yields between an 11 and 177% increase in the likelihood of drug
      choice on average across drugs. Physicians were more likely to use drugs with
      which they had experience, had more citations, and were FDA-approved to treat
      breast cancer. Oncologists are susceptible to financial incentives when choosing
      drugs, though other factors play a large role in their choice of drug.

PMID- 23124973
TI  - Direct and indirect use of GFP whole cell biosensors for the assessment of
      bioprocess performances: design of milliliter scale-down bioreactors.
AB  - Substrate limitation responsive biosensors have been used for the development of
      a mini-bioreactor platform that can be used as a scale-down tool. Three green
      fluorescent protein (GFP) transcriptional reporters have been chosen in
      Escherichia coli, i.e., uspA::gfp, csiE::gfp, and yciG::gfp. Our previous studies
      have shown that these kinds of promoters are induced in response to substrate
      limitation and are significantly repressed when cultures are carried out in
      heterogeneous bioreactors. This sensitivity to substrate limitation has been
      confirmed in the case of the csiE and yciG biosensors. A mini-scale-down platform
      is proposed as a high throughput tool to rapidly investigate the usefulness of a
      given microbial biosensor. This platform is composed of shake flasks able to
      operate in fed-batch mode either using the slow release or the intermittent
      feeding principle. Local heterogeneities were reproduced at the level of these
      mini-bioreactors (operating under the intermittent feeding principle) and caused
      a decrease in GFP expression as in conventional scale-down reactors. The presence
      of GFP in supernatants was also noted and seems to be correlated with the
      substrate limitation signal for the three cultivation systems considered in this
      work (i.e., chemostat, conventional and mini-bioreactors) and with membrane
      permeability.

PMID- 23124974
TI  - High-temperature operating non-volatile memory of printable single-wall carbon
      nanotubes self-assembled with a conjugate block copolymer.
AB  - Printable non-volatile polymer memories are fabricated with solution-processed
      nanocomposite films of poly(styrene-block-paraphenylene) (PS-b-PPP) and single
      wall carbon nanotubes (SWNTs). The devices show stable data retention at high
      temperatures of up to 100  degrees C without significant performance degradation
      due to the strong, non-destructive, and isomorphic pi-pi interactions between the
      SWNTs and PPP block.

PMID- 23124975
TI  - Imitation and speech: commonalities within Broca's area.
AB  - The so-called embodiment of communication has attracted considerable interest.
      Recently a growing number of studies have proposed a link between Broca's area's
      involvement in action processing and its involvement in speech. The present
      quantitative meta-analysis set out to test whether neuroimaging studies on
      imitation and overt speech show overlap within inferior frontal gyrus. By means
      of activation likelihood estimation (ALE), we investigated concurrence of brain
      regions activated by object-free hand imitation studies as well as overt speech
      studies including simple syllable and more complex word production. We found
      direct overlap between imitation and speech in bilateral pars opercularis (BA 44)
      within Broca's area. Subtraction analyses revealed no unique localization neither
      for speech nor for imitation. To verify the potential of ALE subtraction analysis
      to detect unique involvement within Broca's area, we contrasted the results of a
      meta-analysis on motor inhibition and imitation and found separable regions
      involved for imitation. This is the first meta-analysis to compare the neural
      correlates of imitation and overt speech. The results are in line with the
      proposed evolutionary roots of speech in imitation. 

PMID- 23124976
TI  - Co-hydrolysis of lignocellulosic biomass for microbial lipid accumulation.
AB  - The herbaceous perennial energy crops miscanthus, giant reed, and switchgrass,
      along with the annual crop residue corn stover, were evaluated for their
      bioconversion potential. A co-hydrolysis process, which applied dilute acid
      pretreatment, directly followed by enzymatic saccharification without
      detoxification and liquid-solid separation between these two steps was
      implemented to convert lignocellulose into monomeric sugars (glucose and xylose).
      A factorial experiment in a randomized block design was employed to optimize the
      co-hydrolysis process. Under the optimal reaction conditions, corn stover
      exhibited the greatest total sugar yield (glucose + xylose) at 0.545 g g(-1) dry
      biomass at 83.3% of the theoretical yield, followed by switch grass (0.44 g g(-1)
      dry biomass, 65.8% of theoretical yield), giant reed (0.355 g g(-1) dry biomass,
      64.7% of theoretical yield), and miscanthus (0.349 g g(-1) dry biomass, 58.1% of
      theoretical yield). The influence of combined severity factor on the
      susceptibility of pretreated substrates to enzymatic hydrolysis was clearly
      discernible, showing that co-hydrolysis is a technically feasible approach to
      release sugars from lignocellulosic biomass. The oleaginous fungus Mortierella
      isabellina was selected and applied to the co-hydrolysate mediums to accumulate
      fungal lipids due to its capability of utilizing both C5 and C6 sugars. Fungal
      cultivations grown on the co-hydrolysates exhibited comparable cell mass and
      lipid production to the synthetic medium with pure glucose and xylose. These
      results elucidated that combining fungal fermentation and co-hydrolysis to
      accumulate lipids could have the potential to enhance the utilization efficiency
      of lignocellulosic biomass for advanced biofuels production.

PMID- 23124977
TI  - Genomic ancestry of rural African-derived populations from Southeastern Brazil.
AB  - OBJECTIVES: xMany Africans were brought to Brazil as slaves. The runaway or
      abandoned slaves founded isolated communities named quilombos. There are many
      quilombo remnants in Vale do Ribeira region in the southern part of Sao Paulo
      State. The aim of our study was to contribute to understanding the origins of
      these populations, through admixture studies. METHODS: We genotyped 307 unrelated
      DNA samples obtained from ten quilombo populations from Vale do Ribeira region,
      using a panel of 48 INDEL polymorphisms. We estimated genetic differentiation
      between populations (F(ST) ) and genomic ancestry from these populations. Our
      data were compared to a similar study performed in quilombo remnants from the
      Brazilian Amazon region. RESULTS: Population admixture estimates showed high
      degree of miscegenation in the quilombo remnants from Vale do Ribeira (average
      admixture estimates at 39.7% of African, 39.0% of European and 21.3% of
      Amerindian contribution). The proportions of ancestral genes varied greatly among
      individuals, ranging from 7.3 to 69.5%, 12.9 to 68.3%, and 7.3 to 58.5% (African,
      European, and Amerindian, respectively). Genetic differentiation between these
      populations was low (all F(ST) values <5%), indicating gene flow between them.
      Both groups of quilombos, from Vale do Ribeira and Amazon, presented similar
      patterns of admixture. CONCLUSIONS: INDEL markers were useful to evidence the
      triple interbreeding among African, European, and Amerindian in the formation of
      quilombo populations. The low F(ST) values suggested gene flow among quilombos
      from Vale do Ribeira. Our data highlight the important role of Amerindians in the
      formation of quilombo populations.

PMID- 23124978
TI  - Thermoelectric characterization of bismuth telluride nanowires, synthesized via
      catalytic growth and post-annealing.
AB  - Bi(2) Te(3)  nanowires are of significant interest for two fields: nanostructured
      thermoelectrics and topological insulators. The vapor-liquid-solid method is
      employed in combination with annealing in a Te atmosphere, to obtain single
      crystalline Bi(2) Te(3)  nanowires with reproducible electronic transport
      properties (electrical conductivity and Seebeck coefficient) that are close to
      those of intrinsic bulk Bi(2) Te(3) .

PMID- 23124980
TI  - Counterintuitive influence of protonation on radical-anion photoionization.
AB  - Protonation of a radical anion M(.-) greatly facilitates its green-light
      photoionization despite much less favorable energetics for the resulting ketyl
      radical MH(.). The state symmetry of the radical species absorbing the ionizing
      photon might provide an explanation.

PMID- 23124982
TI  - Commissural axons of the mouse cochlear nucleus.
AB  - The axons of commissural neurons that project from one cochlear nucleus to the
      other were studied after labeling with anterograde tracer. Injections were made
      into the dorsal subdivision of the cochlear nucleus in order to restrict labeling
      only to the group of commissural neurons that gave off collaterals to, or were
      located in, this subdivision. The number of labeled commissural axons in each
      injection was correlated with the number of labeled radiate multipolar neurons,
      suggesting radiate neurons as the predominant origin of the axons. The radiate
      commissural axons are thick and myelinated, and they exit the dorsal acoustic
      stria of the injected cochlear nucleus to cross the brainstem in the dorsal half,
      near the crossing position of the olivocochlear bundle. They enter the opposite
      cochlear nucleus via the dorsal and ventral acoustic stria and at its medial
      border. Reconstructions of single axons demonstrate that terminations are mostly
      in the core and typically within a single subdivision of the cochlear nucleus.
      Extents of termination range from narrow to broad along both the dorsoventral
      (i.e., tonotopic) and the rostrocaudal dimensions. In the electron microscope,
      labeled swellings form synapses that are symmetric (in that there is little
      postsynaptic density), a characteristic of inhibitory synapses. Our labeled axons
      do not appear to include excitatory commissural axons that end in edge regions of
      the nucleus. Radiate commissural axons could mediate the broadband inhibition
      observed in responses to contralateral sound, and they may balance input from the
      two ears with a quick time course.

PMID- 23124984
TI  - In vivo tracking of segmental bone defect healing reveals that callus patterning
      is related to early mechanical stimuli.
AB  - This study addresses the hypothesis that callus formation, patterning, and
      mineralisation are impaired during the early phase of critical sized bone defect
      healing, and may relate to inter-fragmentary tissue strains within the bone
      defect area. Twenty four 12 week old Sprague Dawley rats were used for this
      study. They were divided into two groups defined by the femur bone defect size:
      (i) 1 mm resulting in normal healing (NH), and (ii) a large sized 5 mm defect
      resulting in critical healing (CH). Callus formation, patterning, and
      mineralisation kinetics in both groups were examined in the periosteal and
      osteotomy gap regions using a novel longitudinal study setup. Finite element
      analyses on uCT generated tomograms were used to determine inter-fragmentary
      tissue strain patterns and compared to callus formation and patterning over the
      course of time. Using a novel longitudinal study technique with uCT, in vivo
      tracking and computer simulation approaches, this study demonstrates that: (i)
      periosteal bone formation and patterning are significantly influenced by bone
      defect size as early as 2 weeks; (ii) osteotomy gap callus formation and
      patterning are influenced by bone defect size, and adapt towards a non-union in
      critical cases by deviating into a medullary formation route as early as 2 weeks
      after osteotomy; (iii) the new bone formation in the osteotomy gap enclosing the
      medullary cavity in the CH group is highly mineralised; (iv) inter-fragmentary
      strain patterns predicted during the very early soft callus tissue phase (less
      than 2 weeks) are concurrent with callus formation and patterning at later
      stages. In conclusion, bone defect size influences early onset of critical
      healing patterns.

PMID- 23124983
TI  - Slowing down DNA translocation through a nanopore by lowering fluid temperature.
AB  - In the next-generation nanopore-based DNA sequencing technique, the DNA
      nanoparticles are electrophoretically driven through a nanopore by an external
      electric field, and the ionic current through the nanopore is simultaneously
      altered and recorded during the DNA translocation process. The change in the
      ionic current through the nanopore as the DNA molecule passes through the
      nanopore represents a direct reading of the DNA sequence. Due to the large
      mismatch of the cross-sectional areas of the nanopore and the microfluidic
      reservoirs, the electric field inside the nanopore is significantly higher than
      that in the fluid reservoirs. This results in high-speed DNA translocation
      through the nanopore and consequently low read-out accuracy on the DNA sequences.
      Slowing down DNA translocation through the nanopore thus is one of the challenges
      in the nanopore-based DNA sequencing technique. Slowing down DNA translocation by
      lowering the fluid temperature is theoretically investigated for the first time
      using a continuum model, composed of the coupled Poisson-Nernst-Planck equations
      for the ionic mass transport and the Navier-Stokes equations for the hydrodynamic
      field. The results qualitatively agree with the existing experimental results.
      Lowering the fluid temperature from 25 to 0 degrees C reduces the translocation
      speed by a magnitude of about 6.21 to 2.50 mm/sK (i.e. 49.82 to 49.71%) for the
      salt concentration at 200 and 2000 mM, respectively, improving the read-out
      accuracy considerably. As the fluid temperature decreases, the magnitude of the
      ionic current signal decreases (increases) when the salt concentration is high
      (sufficiently low).

PMID- 23124985
TI  - Visible-light-induced photocatalytic reductive transformations of organohalides.

PMID- 23124986
TI  - Monosodium iodoacetate induces apoptosis via the mitochondrial pathway involving
      ROS production and caspase activation in rat chondrocytes in vitro.
AB  - Monosodium iodoacetate (MIA) is an inhibitor of glyceraldehyde-3-phosphate
      dehydrogenase activity, and causes dose-dependent cartilage degradation
      resembling the pathological changes of human osteoarthritis (OA). In this study,
      we assessed the apoptosis induced by MIA and clarified the underlying mechanisms
      using the primary rat chondrocytes. The apoptosis of primary rat chondrocytes was
      analyzed by flow cytometry. The levels of mitochondrial membrane potential
      (DeltaPsim) were evaluated using fluorescence spectrophotometer. The production
      of reactive oxygen species (ROS) was determined by fluorescence
      spectrophotometer. Apoptosis-related protein cytochrome c and procaspase-3
      expressions were examined by Western blotting. We found that MIA treatment
      induces apoptosis in chondrocytes, as confirmed by increases in the percent of
      apoptotic cells, up-regulation of cytochrome c and caspase-3 protein levels.
      Treatment with MIA increases ROS production and decreases the levels of
      DeltaPsim. The antioxidant, N-acetylcysteine (NAC), significantly prevented the
      production of ROS, the reduction of DeltaPsim, the release of cytochrome c and
      the activation of caspase-3. Further, NAC completely protected the cells from MIA
      induced apoptosis. Together these observations suggest that the mechanisms of MIA
      induced apoptosis are primarily via ROS production and mitochondria-mediated
      caspase-3 activation in primary rat chondrocytes.

PMID- 23124987
TI  - Tracking injectable microspheres in dynamic tissues with encapsulated
      superparamagnetic iron oxide nanoparticles.
AB  - Trackable spheres of similar size to those typically used for sustained protein
      delivery are prepared by incorporating superparamagnetic iron oxide (SPIO)
      nanoparticles into the core of poly(lactide-co-glycolide) microspheres. The
      visibility of injections in static and temporally in dynamic tissue systems is
      demonstrated. This method improves upon other, less sensitive imaging modalities
      in their ability to track injectable delivery systems. The results obtained
      confirm the localization of microspheres to the injected target area and
      highlight the novelty of tracking delivery vehicles for other applications.

PMID- 23124989
TI  - Reply: The effect of triple therapy versus etanercept plus methotrexate in
      rheumatoid arthritis: comment on the article by Moreland et al.

PMID- 23124988
TI  - Microtubule modifications and stability are altered by cilia perturbation and in
      cystic kidney disease.
AB  - Disruption of the primary cilium is associated with a growing number of human
      diseases collectively termed ciliopathies. Ciliopathies present with a broad
      range of clinical features consistent with the near ubiquitous nature of the
      organelle and its role in diverse signaling pathways throughout development and
      adult homeostasis. The clinical features associated with cilia dysfunction can
      include such phenotypes as polycystic kidneys, skeletal abnormalities, blindness,
      anosmia, and obesity. Although the clinical relevance of the primary cilium is
      evident, the effects that cilia dysfunction has on the cell and how this
      contributes to disease remains poorly understood. Here, we show that loss of
      ciliogenesis genes such as Ift88 and Kif3a lead to increases in post
      translational modifications on cytosolic microtubules. This effect was observed
      in cilia mutant kidney cells grown in vitro and in vivo in cystic kidneys. The
      hyper-acetylation of microtubules resulting from cilia loss is associated with
      both altered microtubule stability and increased alpha-tubulin acetyl-transferase
      activity. Intriguingly, the effect on microtubules was also evident in renal
      samples from patients with autosomal recessive polycystic kidneys. These findings
      indicate that altered microtubule post-translational modifications may influence
      some of the phenotypes observed in ciliopathies.

PMID- 23124990
TI  - Effects of heel lifting on transtibial amputee gait before and after treadmill
      walking: a case study.
AB  - BACKGROUND: Prosthetic alignment is usually unchanged once optimized. However, a
      previous study indicated that long-distance walking significantly altered gait
      patterns, suggesting some alignment adjustments after walking are required. This
      study investigated the effects of alignment changes (by inserting a heel lift) on
      gait of a transtibial amputee before and after treadmill walking. CASE
      DESCRIPTION AND METHODS: The subject walked, without heel lifts, on a treadmill
      until perception of fatigue. Gait changes upon heel lifting at the prosthetic
      side were studied before and after the treadmill walking FINDINGS AND OUTCOMES:
      For this subject before the treadmill walking, heel lifting induced drop-off with
      increased prosthetic-side knee flexion at mid-stance and pre-swing. The sound
      limb outreached to stabilize the gait. After the treadmill walking, the same heel
      lift did not induce drop-off. It reduced the plantar flexor power generation,
      potentially delaying its fatigue. CONCLUSION: After walking prosthetic-side heel
      lifting could be beneficial. CLINICAL RELEVANCE: Many lower-limb amputees have
      difficulties in long-distance walking due to muscle fatigue. This case study
      proposes that appropriate alignment changes after some walking potentially
      relieve fatigue and encourage them to walk longer distances.

PMID- 23124991
TI  - Performance of elite seated discus throwers in F30s classes: part II: does feet
      positioning matter?
AB  - BACKGROUND: Studies on the relationship between performance and design of the
      throwing frame have been limited. Part I provided only a description of the whole
      body positioning. OBJECTIVES: The specific objectives were (a) to benchmark feet
      positioning characteristics (i.e. position, spacing and orientation) and (b) to
      investigate the relationship between performance and these characteristics for
      male seated discus throwers in F30s classes. STUDY DESIGN: Descriptive analysis.
      METHODS: A total of 48 attempts performed by 12 stationary discus throwers in F33
      and F34 classes during seated discus throwing event of 2002 International
      Paralympic Committee Athletics World Championships were analysed in this study.
      Feet positioning was characterised by tridimensional data of the front and back
      feet position as well as spacing and orientation corresponding to the distance
      between and the angle made by both feet, respectively. RESULTS: Only 4 of 30 feet
      positioning characteristics presented a coefficient correlation superior to 0.5,
      including the feet spacing on mediolateral and anteroposterior axes in F34 class
      as well as the back foot position and feet spacing on mediolateral axis in F33
      class. CONCLUSIONS: This study provided key information for a better
      understanding of the interaction between throwing technique of elite seated
      throwers and their throwing frame. CLINICAL RELEVANCE: This study aimed at
      improving the understanding of the relationship between performance and the
      design of the throwing frame of seated discus throwers, with a particular
      emphasis on the importance of feet positioning. This knowledge is particularly
      important in the current debate around general principles underlying design of
      throwing frame and classification of athletes with a disability, including those
      with lower limb amputation.

PMID- 23124993
TI  - A novel counter-selection method for markerless genetic modification in
      Synechocystis sp. PCC 6803.
AB  - The cyanobacterium Synechocystis sp. PCC 6803 is a photosynthetic organism
      capable of efficient harnessing of solar energy while capturing CO(2) from the
      environment. Methods to genetically alter its genomic DNA are essential for
      elucidating gene functions and are useful tools for metabolic engineering. In
      this study, a novel counter-selection method for the genetic alteration of
      Synechocystis was developed. This method utilizes the nickel inducible expression
      of mazF, a general protein synthesis inhibitor, as a counter-selection marker.
      Counter-selection is particularly useful because the engineered strain is free of
      any markers which make further genetic modification independent of available
      antibiotic resistance genes. The usability of this method was further
      demonstrated by altering genes at several loci in two variants of Synechocystis.

PMID- 23124992
TI  - Impact of esophageal cancer staging on overall survival and disease-free survival
      based on the 2010 AJCC classification by lymph nodes.
AB  - This retrospective study investigated the effect of modifications presented in
      the seventh edition of the American Joint Committee on Cancer (AJCC) Manual for
      staging esophageal cancer on the characterization of the effectiveness of post
      operative chemotherapy and/or radiotherapy, as measured by overall and disease
      free survival. The seventh edition of the AJCC Manual classifies the number of
      lymph nodes (N) positive for regional metastasis into three subclasses. We used
      the AJCC classification system to characterize the cancers of 413 Chinese
      patients with esophageal cancer who underwent radical resection plus regional
      lymph node dissection over a 10-year period. The 10-year survival rate was 14.3%
      for stage N1 patients and 6.1% for stage N2 patients. Only one stage N3 patient
      was followed >4 years (53.4 months). The 10-year disease-free rate was 13.6% for
      stage N1 patients. Patients with stage N2 or N3 cancer were more likely to have
      tumor recurrences, metastases or death than patients with stage N1 cancer. Post
      operative radiotherapy provided no survival benefit, and may have had a negative
      effect on survival. In this study, the N stage of esophageal cancer was an
      independent factor affecting overall and disease-free survival. Our results did
      not clarify whether or not radiotherapy after radical esophagectomy offers any
      survival benefit to patients with esophageal cancer.

PMID- 23124994
TI  - Artificial spores: cytocompatible encapsulation of individual living cells within
      thin, tough artificial shells.
AB  - Cells are encapsulated individually within thin and tough shells in a
      cytocompatible way, by mimicking the structure of bacterial endospores that
      survive under hostile conditions. The 3D 'cell-in-shell' structures-coined as
      'artificial spores'-enable modulation and control over cellular metabolism, such
      as control of cell division, resistance to external stresses, and surface
      functionalizability, providing a useful platform for applications, including cell
      based sensors, cell therapy, regenerative medicine, as well as for fundamental
      studies on cellular metabolism at the single-cell level and cell-to-cell
      communications. This Concept focuses on chemical approaches to single-cell
      encapsulation with artificial shells for creating artificial spores, including
      cross-linked layer-by-layer assembly, bioinspired mineralization, and mussel
      inspired polymerization. The current status and future prospects of this emerging
      field are also discussed.

PMID- 23124995
TI  - A set of specific miRNAs is connected with murine and human gastric cancer.
AB  - MircoRNAs as a new class of regulatory molecules have been investigated in many
      specific cells and organs in healthy and diseased conditions. Although miRNA
      signatures can be directly assessed in patients' affected tissues such as tumor
      sections, recent studies revealed that miRNA profiles can also be obtained
      indirectly, that is, from the patients' peripheral blood. For better
      understanding of miRNA's contribution to gastric carcinoma (one of the leading
      causes of cancer-related mortality worldwide), we screened for deregulated miRNAs
      in blood collected from human cancer patients and compared the expression
      patterns with a gastric carcinoma mouse model (Tff1 knock-out). The profiles were
      assessed using species-specific miRNA microarrays. Among many dozens of
      deregulated miRNAs (219 in H. sapiens; 75 in M. musculus), a subset of eight
      miRNAs comparable in sequence from both species was noted. By in silico analysis,
      their involvement in targeting neoplastic and MAPkinase pathways was
      demonstrated. We found a high probability of linkage of all noted miRNAs to
      pathways in cancer with P-values of 0.013 and 0.018 in mice and humans,
      respectively. Linkage to the MAPK-signaling pathway in mice was observed with a P
      value of 0.01. Moreover, when comparing the 219 deregulated miRNAs obtained from
      blood with deregulated miRNAs derived from gastric cancer (GC) tissues, as
      published previously, 24 miRNAs were identical. If confirmed in a larger patient
      pool, these miRNAs could constitute appropriate blood-born biomarkers for GC.

PMID- 23124996
TI  - Donation after cardiac death liver transplantation: another fly in the ointment.

PMID- 23124997
TI  - Balancing redox cofactor generation and ATP synthesis: key microaerobic responses
      in thermophilic fermentations.
AB  - Geobacillus thermoglucosidasius is a Gram-positive, thermophilic bacterium
      capable of ethanologenic fermentation of both C5 and C6 sugars and may have
      possible use for commercial bioethanol production [Tang et al., 2009; Taylor et
      al. (2009) Trends Biotechnol 27(7): 398-405]. Little is known about the
      physiological changes that accompany a switch from aerobic (high redox) to
      microaerobic/fermentative (low redox) conditions in thermophilic organisms. The
      changes in the central metabolic pathways in response to a switch in redox
      potential were analyzed using quantitative real-time PCR and proteomics. During
      low redox (fermentative) states, results indicated that glycolysis was uniformly
      up-regulated, the Krebs (tricarboxylic acid or TCA) cycle non-uniformly down
      regulated and that there was little to no change in the pentose phosphate
      pathway. Acetate accumulation was accounted for by strong down-regulation of the
      acetate CoA ligase gene (acs) in addition to up-regulation of the pta and ackA
      genes (involved in acetate production), thus conserving ATP while reducing flux
      through the TCA cycle. Substitution of an NADH dehydrogenase (down-regulated) by
      an up-regulated NADH:FAD oxidoreductase and up-regulation of an ATP synthase
      subunit, alongside the observed shifts in the TCA cycle, suggested that an oxygen
      scavenging electron transport chain likely remained active during low redox
      conditions. Together with the observed up-regulation of a glyoxalase and down
      regulation of superoxide dismutase, thought to provide protection against the
      accumulation of toxic phosphorylated glycolytic intermediates and reactive oxygen
      species, respectively, the changes observed in G. thermoglucosidasius NCIMB 11955
      under conditions of aerobic-to-microaerobic switching were consistent with
      responses to low pO(2) stress.

PMID- 23124998
TI  - Influence of age on wound healing and fibrosis.
AB  - The incidence and severity of fibrotic lung diseases increase with age, but very
      little is known about how age-related changes affect the mechanisms that underlie
      disease emergence and progression. Normal ageing includes accumulation of DNA
      mutations, oxidative and cell stresses, mitochondria dysfunction, increased
      susceptibility to apoptosis, telomere length dysfunction and differential gene
      expression as a consequence of epigenetic changes and miR regulation. These
      inevitable ageing-related phenomena may cause dysfunction and impaired repair
      capacity of lung epithelial cells, fibroblasts and MSCs. As a consequence, the
      composition of the extracellular matrix changes and the dynamic interaction
      between cells and their environment is damaged, resulting ultimately in
      predisposition for several diseases. This review summarizes what is known about
      age-related molecular changes that are implicated in the pathobiology of lung
      fibrosis in lung tissue.

PMID- 23125000
TI  - FeCl3-mediated Friedel-Crafts hydroarylation with electrophilic N-acetyl indoles
      for the synthesis of benzofuroindolines.
AB  - IRONic electrophilic indoles! The C3-regioselective hydroarylation of N-acetyl
      indoles with aromatic nucleophiles mediated by FeCl(3)  features a rare example
      of the electrophilic reactivity of the indole core in a Friedel-Crafts reaction.
      This indole umpolung allows us straightforward access to the tetracyclic
      benzofuroindoline motif found in the natural product diazonamide A, which is a
      potent antitumor agent.

PMID- 23124999
TI  - Chemistry as an expanding resource in protein science: fully synthetic and fully
      active human parathyroid hormone-related protein (1-141).

PMID- 23125002
TI  - Free energy simulation of helical transitions.
AB  - An umbrella sampling method for the calculation of free energies for helical
      transitions is presented. The method biases structures toward helices of a
      desired radius and pitch. Although computationally complex, the method has
      negligible overhead in actual applications. To illustrate the method,
      calculations of the helical free energy landscape of several peptides are
      presented for both the CHARMM and the AMBER force fields.

PMID- 23125001
TI  - First-principles calculations of lithium-ion migration at a coherent grain
      boundary in a cathode material, LiCoO(2).
AB  - Results of theoretical calculations are reported, examining the effect of a
      coherent twin boundary on the electrical properties of LiCoO(2) . This study
      suggests that internal interfaces in LiCoO(2)  strongly affect the battery
      voltage, battery capacity, and power density of this material, which is of
      particular concern if it is used in all-solid-state Li-ion batteries.

PMID- 23125003
TI  - Nicotine reduced MMP-9 expression in the primary porcine tenocytes exposed to
      cyclic stretch.
AB  - Nicotine is one of the major chemical components of the cigarette smoke, which
      has been known as a risk factor for tendon ruptures including rotator cuff tears.
      This study investigated the effect of nicotine on tenocytes under cyclic
      stretched condition. Particularly, we focused on the morphologic changes of
      tenocytes and their expression of MMPs. Primary porcine tenocytes were obtained
      from the infraspinatus tendon. The cells were cultured on elastic chambers under
      static or cyclic-stretched condition for 24 h in the existence of nicotine (0, 1,
      10, and 100 uM). Cell shape, gene expression of collagen type I and III, MMPs (
      1, -2, -3, -9, and -13) and TIMPs (-1, -2, and -3) and enzyme activity of MMP-9
      were analyzed using immunohistochemistry, RT-PCR, and zymography. Tenocytes
      exposed to nicotine represented significantly decreased gene expressions in MMP-9
      (p < 0.001) and TIMP-3 (p < 0.05) under the cyclic stretch. Enzymatic activity of
      MMP-9 was also reduced by nicotine exposure in a dose-dependent manner (p <
      0.001). The down-regulation of MMP and TIMP expression by nicotine shown in our
      in vitro experiment might deteriorate normal metabolism of the tendon. These
      mechanisms might affect the mechanical properties of the extracellular matrix of
      the rotator cuff tendon.

PMID- 23125004
TI  - Trajectories of psychological distress after colorectal cancer.
AB  - OBJECTIVE: Heightened psychological distress after cancer is common but likely
      highly heterogeneous. This raises potential challenges in how and when to target
      services; however, data describing longitudinal patterns of distress are limited.
      This study describes the long term psychological outcomes for colorectal cancer
      (CRC) survivors and trajectories of adjustment over time. METHODS: A prospective
      survey of a population-based sample of 1966 CRC survivors assessed
      sociodemographic variables, perceived social support and psychological distress,
      including distress subtypes of anxiety, depression and somatization, at six time
      points from 5 months to 5 years post-diagnosis. RESULTS: Over the 5-year
      trajectory, the prevalence of high overall distress ranged between 44% and 32%
      but was greater for men compared with women (p < 0.001). Four distress trajectory
      styles within clusters were identified for overall distress and for each distress
      subtype with a constant low distress group providing the basis for comparison.
      Higher distress trajectories varied for overall distress and distress subtypes
      but were generally differentiated by gender, younger age, lower education, poor
      socioeconomic advantage, late disease stage and poor social support. CONCLUSIONS:
      For global distress, by comparison with women, men with CRC are vulnerable to
      distress, with men who are younger and with low education and poor social support
      being a priority for targeted intervention. While distress screening early in the
      cancer experience will identify those with a constant high distress trajectory,
      others with late emerging distress or caseness may be missed. On this basis,
      distress screening through the illness trajectory into long term survivorship
      seems warranted.

PMID- 23125005
TI  - Aberrant genes promoter methylation in neural crest-derived tumors.
AB  - Disturbances in the epigenetic landscape by aberrant methylation of CpG islands
      can lead to inactivation of cancer-related genes in solid tumors. We analyzed the
      promoter methylation status of 6 genes previously reported as cancer-specific
      methylated (MCAM, SSBP2, NISCH, B4GALT1, KIF1A and RASSF1A) in 38 neural crest
      derived tumors by quantitative methylation-specific real-time PCR (QMSP). The
      results demonstrated that the determination of the methylation status of RASSF1A
      is able to distinguish between normal and tumor samples in cutaneous melanomas,
      lung carcinoids and small bowel carcinoids. MCAM methylation levels were
      significantly higher in lung carcinoids tumors (p=0.001), suggesting that this
      alteration may represent a molecular biomarker in this tumor type.

PMID- 23125006
TI  - Expression and significance of vascular endothelial growth factor C from multiple
      specimen sources in esophageal squamous cell carcinoma.
AB  - BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a common malignancy with
      a very poor prognosis. Vascular endothelial growth factor C (VEGF-C) plays an
      important role in angiogenesis and lymphangiogenesis. This study was designed to
      analyze the correlation of VEGF-C expression with clinicopathological features
      and survival in multiple specimen sources from patients with ESCC. MATERIAL AND
      METHODS: The expression of VEGF-C in tissues (tVEGF-C), serum (sVEGF-C), and
      lymph fluid (lVEGF-C) from 48 patients with ESCC was detected by different
      methods. RESULTS: There were significant correlations between a high level of
      tVEGF-C expression and tumor differentiation, tumor depth, lymph node metastasis,
      TNM stage and metastasis. sVEGF-C was only significantly related to lymph node
      metastasis, TNM stage and metastasis. The results of lVEGF-C expression were
      similar to those of tVEGG-C expression, but no relationship to tumor depth was
      found. High expression levels of tVEGF-C, sVEGF-C and lVEGF-C were significantly
      associated with shorter overall survival times in univariate analysis (log-rank
      test). CONCLUSIONS: The expression of VEGF-C in multiple specimen sources from
      patients with ESCC was associated with certain clinicopathological parameters.
      High expression of VEGF-C may be an important factor related to a poor prognosis
      of ESCC.

PMID- 23125007
TI  - Survey of KRAS, BRAF and PIK3CA mutational status in 209 consecutive Italian
      colorectal cancer patients.
AB  - Molecular testing for KRAS and BRAF mutations in tumor tissue is a fundamental
      tool to identify patients with metastatic colorectal cancer (CRC) who are
      eligible for anti-EGFR monoclonal antibody therapy. We here report a molecular
      analysis by high-resolution melting analysis and direct sequencing of KRAS, BRAF
      and PIK3CA hot spot mutations in 209 Italian CRC patients. One hundred and ten
      patients (51%) were identified who were potentially nonresponders to anti-EGFR
      therapy: 90/209 patients (43%) harboring KRAS mutations, 13/117 (11.1%) with the
      V600E BRAF mutation, and 7/209 (3.3%) with mutations in PIK3CA exon 20. The
      prevalence of BRAF and PIK3CA mutations was significantly higher in patients
      older than 65 years (p=0.014 and p=0.018), while patients with triple-negative
      tumors were significantly younger than mutation carriers (p=0.000011). Patients
      with gene mutations also showed a trend towards preferential tumor location in
      the colon (p=0.026). Moreover, although involving a relatively small number of
      samples, we report the presence of a discordant mutational profile between
      primary tumors and secondary lesions (3/9 patients), suggesting that it is
      worthwhile to test other available tissues in order to better define the efficacy
      of targeted therapy. Further correlations of specific clinical features with
      tumor mutational profile could be helpful to predict the response of CRC patients
      to monoclonal antibody therapy.

PMID- 23125008
TI  - Expression of beclin 1 in bladder cancer and its clinical significance.
AB  - BACKGROUND: The aim of this study is to explore the expression of beclin 1, an
      autophagy gene, in bladder cancer and to evaluate its clinical and prognostic
      significance in patients with bladder cancer. METHODS: Beclin 1 expression was
      examined at mRNA and protein levels by real-time quantitative polymerase chain
      reaction (RT-PCR), Western blotting, and immunohistochemistry in bladder cancer
      tissues and adjacent normal bladder tissues. The relationship between the
      expression of beclin 1 and clinicopathological characteristics and prognosis was
      statistically analyzed.? RESULTS: mRNA level, protein expression and
      immunoreactivity of beclin 1 were decreased in bladder cancer tissues compared
      with adjacent normal tissues. Downregulation of beclin 1 was more frequent in
      tumors with higher histological grades (the expression of beclin 1 was reduced by
      49.0% in G1 and G2, and by 71.8% in G3, p=0.010), and was also reduced by 69.5%
      in the muscle invasive type and by 51.1% in the non-muscle invasive type
      (p=0.04). Reduced beclin 1 expression was positively associated with higher
      histological grade and more advanced clinical stage (p<0.05). Kaplan-Meier
      survival analysis revealed that patients exhibiting lower beclin 1 expression
      experienced a shorter survival than those with higher expression (p=0.006). Cox
      proportional hazards regression analysis showed that beclin 1 protein is an
      independent predictor of survival (p=0.005).? CONCLUSION: Beclin 1 has an
      influence on the progression of bladder cancer and might serve as a potential
      prognostic factor for patients with bladder cancer.

PMID- 23125009
TI  - Significance of cyclin D1 polymorphisms in patients with head and neck cancer.
AB  - Cyclin D1 plays a key role in cell cycle control, particularly in the transition
      from G1 to S phase, regulated by cyclin-dependent kinases. The objective of the
      present study was to screen the cyclin D1 gene (CCND1) for polymorphisms in
      patients with head and neck cancer (HNC). Genomic DNA was isolated from blood
      samples of 380 HNC patients and 350 controls. In a hospital-based case-control
      study using the PCR-SSCP technique we found 3 novel germline mutations: g3578C>A,
      g3475G>C and g3383delA. The commonly reported guanine to adenine polymorphisms in
      exon 4 g7656G>A (rs9344) and g10861C>A (rs7177) in 3'UTR of CCND1 were also
      observed. The calculated frequencies of the g7656G>A (rs9344) polymorphism in GG,
      GA and AA genotypes were 27.3%, 38.6%, and 33.9% in HNC cases, and 44.2%, 29.4%,
      and 26.2% in normal healthy controls, respectively. Adjusted by age (in years),
      sex and smoking status, multivariate logistic regression analysis showed that the
      AA and GA genotypes were associated with a significantly increased risk (OR 1.34,
      95% CI 1.03-1.64, p=0.028) for HNC. The CCND1 AA genotype variant was associated
      with an increased risk in individuals who were <40 years old (OR 1.45, 95% CI
      1.02-2.08, p=0.04). In conclusion, it is suggested that the CCND1 G/A
      polymorphism is associated with the early onset of HNC and may contribute to HNC
      susceptibility in a Pakistani population.

PMID- 23125010
TI  - Charge-balanced metal fluoride complexes for protein kinase A with adenosine
      diphosphate and substrate peptide SP20.

PMID- 23125011
TI  - Incorporation of prognostic and predictive factors into glioma clinical trials.
AB  - Treatment of brain tumors is increasingly informed by biomarkers that predict
      patient prognosis and response to therapy. While this progress represents a great
      opportunity for the field of neuro-oncology, it also presents significant
      challenges. Biomarkers are not straightforward to identify, and previously used
      clinical trial paradigms are poorly suited to the task of identifying treatments
      effective only in selected subsets of patients. Unless investigators adapt new
      tools and procedures that better account for the biological diversity of gliomas,
      future clinical trials run the dual risk of missing important treatment effects
      and exposing patients to interventions destined to prove ineffective for their
      tumors. In this article, we will review the progress made in the past decade with
      respect to biomarkers in neuro-oncology, address barriers to ongoing progress,
      and discuss clinical trial designs that may prove useful in moving neuro-oncology
      fully into the era of personalized medicine.

PMID- 23125012
TI  - Current and future immunomodulation strategies to restore tolerance in autoimmune
      diseases.
AB  - Autoimmune diseases reflect a breakdown in self-tolerance that results from
      defects in thymic deletion of potentially autoreactive T cells (central
      tolerance) and in T-cell intrinsic and extrinsic mechanisms that normally control
      potentially autoreactive T cells in the periphery (peripheral tolerance). The
      mechanisms leading to autoimmune diseases are multifactorial and depend on a
      complex combination of genetic, epigenetic, molecular, and cellular elements that
      result in pathogenic inflammatory responses in peripheral tissues driven by self
      antigen-specific T cells. In this article, we describe the different checkpoints
      of tolerance that are defective in autoimmune diseases as well as specific events
      in the autoimmune response which represent therapeutic opportunities to restore
      long-term tolerance in autoimmune diseases. We present evidence for the role of
      different pathways in animal models and the therapeutic strategies targeting
      these pathways in clinical trials in autoimmune diseases.

PMID- 23125013
TI  - Intercellular interactions, position, and polarity in establishing blastocyst
      cell lineages and embryonic axes.
AB  - The formation of the three lineages of the mouse blastocyst provides a powerful
      model system to study interactions among cell behavior, cell signaling, and
      lineage development. Hippo signaling differences between the inner and outer
      cells of the early cleavage stages, combined with establishment of a stably
      polarized outer epithelium, lead to the establishment of the inner cell mass and
      the trophectoderm, whereas FGF signaling differences among the individual cells
      of the ICM lead to gradual separation and segregation of the epiblast and
      primitive endoderm lineages. Events in the late blastocyst lead to the formation
      of a special subset of cells from the primitive endoderm that are key sources for
      the signals that establish the subsequent body axis. The slow pace of mouse early
      development, the ability to culture embryos over this time period, the increasing
      availability of live cell imaging tools, and the ability to modify gene
      expression at will are providing increasing insights into the cell biology of
      early cell fate decisions.

PMID- 23125014
TI  - Primordial germ cells in mice.
AB  - Germ cell development creates totipotency through genetic as well as epigenetic
      regulation of the genome function. Primordial germ cells (PGCs) are the first
      germ cell population established during development and are immediate precursors
      for both the oocytes and spermatogonia. We here summarize recent findings
      regarding the mechanism of PGC development in mice. We focus on the
      transcriptional and signaling mechanism for PGC specification, potential
      pluripotency, and epigenetic reprogramming in PGCs and strategies for the
      reconstitution of germ cell development using pluripotent stem cells in culture.
      Continued studies on germ cell development may lead to the generation of
      totipotency in vitro, which should have a profound influence on biological
      science as well as on medicine.

PMID- 23125015
TI  - The role of the apoptotic machinery in tumor suppression.
AB  - Multicellular organisms have evolved processes to prevent abnormal proliferation
      or inappropriate tissue infiltration of cells, and these tumor suppressive
      mechanisms serve to prevent tissue hyperplasia, tumor development, and metastatic
      spread of tumors. These include potentially reversible processes such as cell
      cycle arrest and cellular senescence, as well as apoptotic cell death, which in
      contrast eliminates dangerous cells that may initiate tumor development. Tumor
      suppressive processes are organized as complex, extensive signaling networks,
      controlled by central "nodes." These "nodes" are prominent tumor suppressors,
      such as P53 or PTEN, whose loss is responsible for the development of the
      majority of human cancers. In this review we discuss the processes by which some
      of these prominent tumor suppressors trigger apoptotic cell death and how this
      process protects us from cancer development.

PMID- 23125017
TI  - MAP kinase pathways.

PMID- 23125016
TI  - Fueling the flames: Mammalian programmed necrosis in inflammatory diseases.
AB  - Programmed necrosis or necroptosis is an inflammatory form of cell death driven
      by TNF-like death cytokines, toll-like receptors, and antigen receptors. Unlike
      necrosis induced by physical trauma, a dedicated pathway is involved in
      programmed necrosis. In particular, a kinase complex composed of the receptor
      interacting protein kinase 1 (RIPK1) and RIPK3 is a central step in necrotic cell
      death. Assembly and activation of this RIPK1-RIPK3 "necrosome" is critically
      controlled by protein ubiquitination, phosphorylation, and caspase-mediated
      cleavage events. The molecular signals cumulate in formation of intracellular
      vacuoles, organelle swelling, internal membrane leakage, and eventually plasma
      membrane rupture. These morphological changes can result in spillage of
      intracellular adjuvants to promote inflammation and further exacerbate tissue
      injury. Because of the inflammatory nature of necrosis, it is an attractive
      pathway for therapeutic intervention in acute inflammatory diseases.

PMID- 23125018
TI  - Mitochondrial quality control mediated by PINK1 and Parkin: links to
      parkinsonism.
AB  - Mutations in Parkin or PINK1 are the most common cause of recessive familial
      parkinsonism. Recent studies suggest that PINK1 and Parkin form a mitochondria
      quality control pathway that identifies dysfunctional mitochondria, isolates them
      from the mitochondrial network, and promotes their degradation by autophagy. In
      this pathway the mitochondrial kinase PINK1 senses mitochondrial fidelity and
      recruits Parkin selectively to mitochondria that lose membrane potential. Parkin,
      an E3 ligase, subsequently ubiquitinates outer mitochondrial membrane proteins,
      notably the mitofusins and Miro, and induces autophagic elimination of the
      impaired organelles. Here we review the recent rapid progress in understanding
      the molecular mechanisms of PINK1- and Parkin-mediated mitophagy and the
      identification of Parkin substrates suggesting how mitochondrial fission and
      trafficking are involved. We also discuss how defects in mitophagy may be linked
      to Parkinson's disease.

PMID- 23125019
TI  - Disulfide bond formation in the mammalian endoplasmic reticulum.
AB  - The formation of disulfide bonds between cysteine residues occurs during the
      folding of many proteins that enter the secretory pathway. As the polypeptide
      chain collapses, cysteines brought into proximity can form covalent linkages
      during a process catalyzed by members of the protein disulfide isomerase family.
      There are multiple pathways in mammalian cells to ensure disulfides are
      introduced into proteins. Common requirements for this process include a
      disulfide exchange protein and a protein oxidase capable of forming disulfides de
      novo. In addition, any incorrect disulfides formed during the normal folding
      pathway are removed in a process involving disulfide exchange. The pathway for
      the reduction of disulfides remains poorly characterized. This work will cover
      the current knowledge in the field and discuss areas for future investigation.

PMID- 23125023
TI  - Features of transport in ultrathin gold nanowire structures.
AB  - The origin of the interface formation appearing due to the realization of
      contacts to ultrathin gold nanowire devices is revealed. Such interfaces play an
      important role in transport mechanisms in nanowire structures and can determine
      the electrical and operating parameters of a nanodevice. Based on experimental
      results, the specific electrical properties of bundles of ultrathin gold
      nanowires fabricated by wet chemical synthesis and subsequently assembled and
      contacted with gold electrodes are reported. It is demonstrated that these
      properties are strongly affected by the monolayers of organic molecules
      inevitably present on the surface of the nanowires due to synthetic conditions.
      In particular, such layers form a potential barrier to tunneling of the electrons
      from contacts to the nanowires. The electric transport behavior of the
      investigated nanowire structures in the temperature range from 500 mK to 300 K
      obeys the model of thermal fluctuation-induced tunneling conduction through the
      nanowire-metal electrode molecular junction. Application of this model allows
      calculation of the parameters of the molecular potential barrier. The formation
      of such a molecular barrier is verified by scanning tunneling microscope (STM)
      and transmission electron microscope (TEM) measurements performed using a
      supporting graphene layer. These findings are important for designing novel
      nanodevices for molecular electronics on the basis of ultrathin nanowires.

PMID- 23125021
TI  - miR-10b*, a master inhibitor of the cell cycle, is down-regulated in human breast
      tumours.
AB  - Deregulated proliferation is a hallmark of cancer cells. Here, we show that
      microRNA-10b* is a master regulator of breast cancer cell proliferation and is
      downregulated in tumoural samples versus matched peritumoural counterparts. Two
      canonical CpG islands (5 kb) upstream from the precursor sequence are
      hypermethylated in the analysed breast cancer tissues. Ectopic delivery of
      synthetic microRNA-10b* in breast cancer cell lines or into xenograft mouse
      breast tumours inhibits cell proliferation and impairs tumour growth in vivo,
      respectively. We identified and validated in vitro and in vivo three novel target
      mRNAs of miR-10b* (BUB1, PLK1 and CCNA2), which play a remarkable role in cell
      cycle regulation and whose high expression in breast cancer patients is
      associated with reduced disease-free survival, relapse-free survival and
      metastasis-free survival when compared to patients with low expression. This also
      suggests that restoration of microRNA-10b* expression might have therapeutic
      promise.

PMID- 23125024
TI  - Superresolution STED microscopy reveals differential localization in primary
      cilia.
AB  - The primary cilium is an organelle that serves as a signaling center of the cell
      and is involved in the cAMP, Wnt, and hedgehog signaling pathways. Adenylyl
      cyclase type III (ACIII) is enriched in primary cilia and acts as a marker that
      is involved in cAMP signaling, while also playing an important role in regulating
      ciliogenesis and sensory functions. Ciliary function relies on the transportation
      of molecules between the primary cilium and the cell, which is facilitated by
      intraflagellar transport (IFT). The detailed localization and interactions of
      these important proteins remain unclear due to the limited resolution of
      conventional microscopy. We conducted superresolution imaging of immunostained
      ACIII and IFT88 in human fibroblasts using stimulated emission depletion (STED)
      microscopy. Instead of a homogeneous distribution along a primary cilium, our
      STED images revealed that ACIII formed a periodic punctate pattern with a roughly
      equal spacing between groups of puncta. Superresolution imaging of IFT88, an
      important protein of the IFT complexes, demonstrated two novel distinct
      distribution patterns at the basal end: a triangle of three puncta with similar
      fluorescence intensities, and a Y-shaped configuration of a bright punctum
      connected to two branches. We also performed STED imaging of IFT88 in mouse inner
      medullary collecting duct cells and mouse embryonic fibroblasts. The similar
      three-puncta and Y-shape patterns were observed in these cells, suggesting that
      these distribution patterns are common among primary cilia of different cell
      types. Our results demonstrate the ability of superresolution STED microscopy to
      reveal novel structural characteristics in primary cilia.

PMID- 23125025
TI  - The effect of triple therapy versus etanercept plus methotrexate in rheumatoid
      arthritis: comment on the article by Moreland et al.

PMID- 23125026
TI  - Targeted nitric oxide delivery preferentially induces glioma cell
      chemosensitivity via altered p53 and O(6) -methylguanine-DNA methyltransferase
      activity.
AB  - Glioblastoma multiforme is the most common malignant central nervous system
      tumor, and also among the most difficult to treat due to a lack of response to
      chemotherapeutics. New methods of countering the mechanisms that confer
      chemoresistance to malignant gliomas could lead to significant advances in the
      quest to identify novel drug combinations or targeted drug delivery systems for
      cancer therapy. In this study, we investigate the use of a targeted nitric oxide
      (NO) donor as a pretreatment to sensitize glioma cells to chemotherapy. The
      protein chlorotoxin (CTX) has been shown to preferentially target glioma cells,
      and we have developed CTX-NO, a glioma-specific, NO-donating CTX derivative.
      Pretreatment of cells with CTX-NO followed by 48-h exposure to either carmustine
      (BCNU) or temozolomide (TMZ), both common chemotherapeutics used in glioma
      treatment, resulted in increased efficacy of both therapeutics. After CTX-NO
      exposure, both T98G and U-87MG human malignant glioma cells show increased
      sensitivity to BCNU and TMZ. Further investigation revealed that the consequences
      of this combination therapy was a reduction in active levels of the
      cytoprotective enzyme MGMT and altered p53 activity, both of which are essential
      in DNA repair and tumor cell resistance to chemotherapy. The combination of CTX
      NO and chemotherapeutics also led to decreased cell invasion. These studies
      indicate that this targeted NO donor could be an invaluable tool in the
      development of novel approaches to treat cancer.

PMID- 23125027
TI  - PARK2 and PACRG are commonly downregulated in clear-cell renal cell carcinoma and
      are associated with aggressive disease and poor clinical outcome.
AB  - PARK2 is an E3 ligase, known to be involved in ubiquitination of several proteins
      and to play a role in neuronal protection. The gene PARK2 and its potentially co
      regulated gene PACRG have been previously found to be deleted in clear-cell renal
      cell carcinomas (ccRCCs). The aim of our study was to evaluate the mRNA and
      protein expression of PARK2 and PACRG in a large cohort of ccRCC, and to
      investigate their association with outcome. The expression of both genes was
      measured by quantitative PCR in 94 primary ccRCCs and autologous nonmalignant
      kidney tissues. PACRG and PARK2 protein expression was determined
      immunohistochemically using tissue microarrays comprising 133 ccRCCs. The mRNA
      and protein expression of PARK2 and PACRG was significantly downregulated in
      ccRCCs compared with nonmalignant tissues. Low levels of PARK2 mRNA were
      associated with high-grade ccRCC and lymph node metastasis. Patients with low
      PARK2 mRNA levels showed a higher tumor-specific mortality rate and a shorter
      overall survival (OS) than those with high PARK2 expression. Patients without
      PACRG mRNA expression in the tumor had a shorter disease-free survival and OS
      than those with tumors expressing PACRG. In multivariate analyses, neither PARK2
      nor PACRG expression were independent prognostic factors. The protein expression
      of PARK2 and PACRG was significantly downregulated in ccRCCs (82.8, and 96.9%,
      respectively), but no association with clinical outcome was noticed.

PMID- 23125028
TI  - Psychometric evaluation of a coping questionnaire in two independent samples of
      people with diabetes.
AB  - The study examines internal item/scale structure and concurrent validity of a
      newly developed 48-item questionnaire [General Coping Questionnaire (GCQ)] that
      measures 10 aspects of coping with chronic illness (self-trust, problem-reducing
      actions, change of values, social trust, minimization, fatalism, resignation,
      protest, isolation and intrusion). The tests were performed in two independent
      samples of persons with diabetes mellitus. The first sample consisted of 119
      subjects with type I diabetes and the second sample of 184 subjects with type II
      diabetes. Concurrent validity was examined by comparisons with measures of health
      related quality of life (SF-36), a measure of metabolic control (HbA1c) and
      incidence of diabetic complications. The item/scale structure was found to be
      similar and very good in both samples. The 10 dimensions correlated as expected
      with the measure of mental health, although the 'negative' dimensions of the GCQ
      correlated higher compared with the 'positive' dimensions. Weaker relations with
      metabolic control were also found in one of the samples. These tests provide
      further evidence that GCQ is a well-structured, relevant and reliable instrument
      for assessing coping reactions in chronic somatic conditions.

PMID- 23125029
TI  - Triple-helical recognition of RNA using 2-aminopyridine-modified PNA at
      physiologically relevant conditions.
AB  - Peptide nucleic acids containing thymidine and 2-aminopyridine (M) nucleobases
      form stable and sequence-selective triple helices with double-stranded RNA at
      physiologically relevant conditions. The M-modified PNA showed unique RNA
      selectivity by having two orders of magnitude higher affinity for the double
      stranded RNAs than for the same DNA sequences.

PMID- 23125030
TI  - Regulation of the immune and inflammatory responses by the 'atypical' chemokine
      receptor D6.
AB  - Chemokines and their receptors are key regulators of leukocyte migration and
      intra-tissue accumulation under both homeostatic and inflammatory conditions.
      Regulation of chemokine-dependent responses, particularly those relating to
      inflammation, is essential to avoid the development of inflammatory and
      autoimmune pathologies. Recently, a new subfamily of chemokine receptors referred
      to as the 'atypical' chemokine receptors has emerged, members of which have been
      shown to play important roles in controlling in vivo chemokine biology. Here we
      review the basic biology of the chemokine and chemokine receptor family,
      introduce the topic of 'atypical' chemokine receptor biology and focus
      specifically on the best-characterized of the 'atypical' chemokine receptors, D6.
      D6 is a 'scavenging' receptor for inflammatory CC chemokines and plays a central
      role in the resolution of in vivo inflammatory responses. We describe the
      biology, biochemistry and pathological relevance of D6 and outline emerging data
      suggesting that it has additional important roles in integrating innate and
      adaptive immune responses.

PMID- 23125031
TI  - Succeeding in the face of stereotype threat: the adaptive role of engagement
      regulation.
AB  - Two experiments examined Engagement Regulation, the systematic increase or
      decrease of self-esteem engagement in a domain following positive or negative
      outcomes, respectively. We hypothesized that, under threat, more positive
      outcomes increase engagement, and greater engagement augments the influence of
      subsequent outcomes on self-esteem and performance. Female participants completed
      an initial math test, received bogus feedback, and then completed a second test.
      Results indicated that more positive feedback evoked greater engagement and that
      this relationship was strongest under stereotype threat (Study 1). Under
      stereotype threat, engagement interacted with subsequent feedback, such that
      greater engagement to positive feedback increased performance, but greater
      engagement to negative feedback decreased self-esteem and performance (Study 2).
      Together, these findings suggest that Engagement Regulation facilitates self
      esteem maintenance and positive performance under stereotype threat.

PMID- 23125032
TI  - Theoretical study on the mechanism and kinetics of addition of hydroxyl radicals
      to fluorobenzene.
AB  - Geometries, frequencies, reaction barriers, and reaction rates were calculated
      for the addition of OH radical to fluorobenzene using Moller-Plesset second-order
      perturbation (MP2) and G3 methods. Four stationary points were found along each
      reaction path: reactants, prereaction complex, transition state, and product. A
      potential for association of OH radical and fluorobenzene into prereaction
      complex was calculated, and the associated transition state was determined for
      the first time. G3 calculations give higher reaction barriers than MP2, but also
      a significantly deeper prereaction complex minimum. The rate constants,
      calculated with Rice-Ramsperger-Kassel-Marcus (RRKM) theory using G3 energies,
      are much faster and in much better agreement with the experiment than those
      calculated with MP2 method, as the deeper well favors the formation of
      prereaction complex and also increases the final relative populations of adducts.
      The discrepancies between the experimental and calculated rate constants are
      attributed to the errors in calculated frequencies as well as to the
      overestimated G3 reaction barriers and underestimated prereaction complex well
      depth. It was possible to rectify those errors and to reproduce the experimental
      reaction rates in the temperature range 230-310 K by treating the relative
      translation of OH radical and fluorobenzene as a two-dimensional particle-in-the
      box approximation and by downshifting the prereaction complex well and reaction
      barriers by 0.7 kcal mol(-1). The isomeric distribution of
      fluorohydroxycyclohexadienyl radicals is calculated from the reaction rates to be
      30.9% ortho, 22.6% meta, 38.4% para, and 8.3% ipso. These results are in
      agreement with experiment that also shows dominance of ortho and para channels.

PMID- 23125033
TI  - Proteome dynamics: revisiting turnover with a global perspective.
AB  - Although bulk protein turnover has been measured with the use of stable isotope
      labeled tracers for over half a century, it is only recently that the same
      approach has become applicable to the level of the proteome, permitting analysis
      of the turnover of many proteins instead of single proteins or an aggregated
      protein pool. The optimal experimental design for turnover studies is dependent
      on the nature of the biological system under study, which dictates the choice of
      precursor label, protein pool sampling strategy, and treatment of data. In this
      review we discuss different approaches and, in particular, explore how complexity
      in experimental design and data processing increases as we shift from unicellular
      to multicellular systems, in particular animals.

PMID- 23125034
TI  - Molecular analysis of the rare in(Lu) blood type: toward decoding the phenotypic
      outcome of haploinsufficiency for the transcription factor KLF1.
AB  - KLF1 encodes an erythroid transcription factor, whose essential function in
      erythropoiesis has been demonstrated by extensive studies in mouse models. The
      first reported mutations in human KLF1 were found in individuals with a rare and
      asymptomatic blood type called In(Lu). Here, we show that KLF1 haploinsufficiency
      is responsible for the In(Lu) blood type, after redefining this peculiar blood
      type using flow cytometry to quantify the levels of BCAM and CD44 on red blood
      cells. We found 10 (seven novel) heterozygous KLF1 mutations responsible for the
      In(Lu) blood type. Although most were obligate loss-of-function mutations due to
      the truncation of the DNA-binding domain of KLF1, three were missense mutations
      that were located in its DNA-binding domain and impaired the transactivation
      capacity of KLF1 in vitro. We further showed that the levels of the hemoglobin
      variants HbF and HbA(2)  were increased in the In(Lu) blood type, albeit
      differently. The levels of the membrane glycoproteins BCAM and CD44 were also
      differently reduced on In(Lu) red blood cells. This biochemical and genetic
      analysis of the In(Lu) blood type tackles the phenotypic outcome of
      haploinsufficiency for a transcription factor.

PMID- 23125035
TI  - Effect of selenophene in a DPP copolymer incorporating a vinyl group for high
      performance organic field-effect transistors.
AB  - A new polymeric semiconductor, PDPPDTSE, is reported which is composed of a
      diketopyrrolopyrrole moiety and selenophenylene vinylene selenophene, with a high
      field-effect mobility achieved through intermolecular donor-acceptor
      interactions. The field-effect mobility of OFET devices based on PDPPDTSE by spin
      casting is 4.97 cm(2)  V(-1)  s(-1) , which is higher than predecessor polymeric
      semiconductors.

PMID- 23125036
TI  - Intrapopulation variation in macro tooth wear patterns--a case study from
      Igloolik, Canada.
AB  - The pattern of human tooth wear-the way it varies between teeth in the mouth-is
      crucial to our understanding of important questions in archeology and
      paleoanthropology, such as the contrasts in diet and behavior between
      Neanderthals and early modern humans in Europe and Asia, or with the adoption of
      agriculture in the Americas. Little is known, however, about the way in which
      wear patterns develop with increasing age or the way in which they differ between
      males and females. One explanation is that few living people show the high rates
      of tooth wear seen worldwide throughout the preindustrial archaeological record.
      The study described here investigates the macroscopic pattern of tooth wear in a
      unique group of known age and sex dental casts from living Canadian Inuit from
      Igloolik. The results show that the Igloolik people possessed a pattern of
      extremely heavy anterior tooth wear, relative to the first molar and the other
      posterior teeth, which is attributed to the use of the anterior teeth in cultural
      practices as well as the extreme and marginal environments in which they lived.
      Heavy anterior tooth wear was established at an early age and maintained
      throughout life; statistically significant differences were found between the
      wear patterns of males and females and are explained in terms of sexual division
      of labor within the community. This study highlights the need to understand both
      intra- and interpopulation variation in tooth wear patterns when interpreting
      patterns in past human groups.

PMID- 23125038
TI  - 1H NMR spectra. Part 29S: Proton chemical shifts and couplings in esters--the
      conformational analysis of methyl gamma-butyrolactones.
AB  - The (1)H NMR spectra of 35 cyclic and acyclic esters are analysed to give the
      (1)H chemical shifts and couplings. The substituent chemical shifts of the ester
      group were analysed using three-bond (gamma) effects for near protons and the
      electric field, magnetic anisotropy and steric effect of the ester group for more
      distant protons. The electric field is calculated from the partial atomic charges
      on the O?C = O atoms, and the asymmetric magnetic anisotropy of the carbonyl
      group acts at the midpoint of the C = O bond. The values of the anisotropies
      Deltachi(parl) and Deltachi(perp) were for the aliphatic esters 10.35 and -18.84
      and for the conjugated esters 7.33 and -15.75 (*10(-6) A(3)/molecule). The oxygen
      steric coefficients found were 104.4 (aliphatic C = O), 45.5 (aromatic C = O) and
      16.0 (C-O) (*10(-6) A(6)/molecule). After parameterisation, the overall RMS error
      for the data set of 280 entries was 0.079 ppm. The strongly coupled (1) H NMR
      spectra of the 2-methyl, 3-methyl and 4-methyl gamma-butyrolactones were analysed
      and the methyl conformational equilibrium obtained from the observed couplings.
      The observed versus calculated density functional theory (DFT) DeltaG(ax-eq) was
      1.0 (1.01), 0.34 (0.54) and 0.65 (0.71) kcal/mol res. The shielding effect of a
      methyl cis to a proton in the five-membered lactone rings is -0.40 +/-0.05 ppm
      and deshielding trans effect 0.12 +/-0.05 ppm, which is common to both five and
      six membered rings. The cis/trans isomerism in the vinyl esters methyl acrylate,
      crotonate and methacrylate and methyl furoate was examined using the (1)H
      chemical shifts. The calculated shifts of both the cis and trans isomers were in
      good agreement with the observed shifts.

PMID- 23125037
TI  - A novel small molecule facilitates the reprogramming of human somatic cells into
      a pluripotent state and supports the maintenance of an undifferentiated state of
      human pluripotent stem cells.
AB  - Booster of pluripotency: RSC133, a new synthetic derivative of indoleacrylic
      acid/indolepropionic acid, exhibits dual activity by inhibiting histone
      deacetylase and DNA methyltransferase. Furthermore it potently improves the
      reprogramming of human somatic cells into a pluripotent state and aids the growth
      and maintenance of human pluripotent stem cells (hPSCs).

PMID- 23125039
TI  - Editorial: Biotechnology's impact on sustainable development.
AB  - Biotechnology is increasingly recognized in society as a technology to improve
      the quality of life in a sustainable manner. It is clear that bioenergy and
      biofuel cannot solve a world energy crisis or reverse global warming, but from a
      local perspective it can contribute a lot.

PMID- 23125042
TI  - Genetically modified mosquito: the Malaysian public engagement experience.
AB  - On December 21, 2010, 6000 genetically modified (GM) mosquitoes were released in
      an uninhabited forest in Malaysia. The purpose of the deliberate release was a
      limited "marked release and recapture" (MRR) experiment, a standard ecological
      method in entomology, to evaluate under field conditions, the flight distance and
      longevity of the sterile male Aedes aegypti strain OX513A(My1), a GM strain. As
      with any other GM technologies, the release was received with mixed responses. As
      the scientific community debate over the public engagement strategies for similar
      GM releases, dengue incidence continues to rise with a heavy toll on morbidity,
      mortality and healthcare budgets. Meanwhile the wild female Aedes aegypti
      continues to breed offspring, surviving and evading conventional interventions
      for vector control.

PMID- 23125046
TI  - TP53*P72 allele influences negatively female life expectancy in a population of
      central Italy: cross-sectional study and genetic-demographic approach analysis.
AB  - The association of TP53 P72R (rs1042522) with longevity remains uncertain and
      varies with ethnicity. Here, we tested its association with longevity in a cross
      sectional population of Central Italy (18-106 years, N = 1,072), by integrating
      demographic information and frequency data to account for the different survival
      rates between sexes through the application of a genetic-demographic approach.
      rs1042522 affects females longevity, showing significant associations in
      Comparison 2 (Age Class 3 [>91 years] vs Age Class 2 [73-91 years]) under both
      additive (odds ratio [OR] 0.574; p = .006) and dominant (OR 0.513; p = .006)
      models. The TP53*P72 allele is significantly underrepresented in Age Class 3 only
      in women (OR 0.575; p = .008). The genetic-demographic approach demonstrated that
      the frequency of female TP53*P72 carriers underwent a significant reduction after
      82 years (OR 0.586; p = .002). The same analyses gave nonsignificant results in
      men. The discrepancies among the results obtained on rs1042522 for longevity
      could result from the pleiotropic effects of p53 and the potential ethnic
      variation of its functional variants.

PMID- 23125047
TI  - The efficacy of rituximab in refractory myositis: the jury is still out.

PMID- 23125048
TI  - Hyperbranched polymeric ionic liquids with onion-like topology as transporters
      and compartmentalized systems.
AB  - A new family of hyperbranched polymeric ionic liquids ("hyperILs") with onion
      like topology and facile polarity design were tailored as transporters and
      compartmentalized systems. Applications include transport and dispersion of water
      soluble dyes and functionalized graphene nanosheets from aqueous phase into
      nonpolar fluids, including polymer melts.

PMID- 23125049
TI  - Harnessing thermal expansion mismatch to form hollow nanoparticles.
AB  - Nano popcorn: a new formation mechanism for the synthesis of hollow metal oxide
      nanoparticles through a melt fracture mechanism. The hollow nanoparticles are
      formed via brittle fracture following the generation of tensile stresses arising
      due to liquid-phase thermal expansion of a low melting point core metal. The
      progress of this physical process can be monitored using in situ transmission
      electron microscopy for a model system of indium/indium oxide.

PMID- 23125050
TI  - Ultrastructure and motility of the spermatozoa of Polypedates leucomystax
      (Amphibia, Anura, Rhacophoridae).
AB  - Sperm morphology is thought to be shaped by evolutionary pressure from the
      fertilization environment. Rhacophoridae (Amphibia, Anura) include both foam
      nesting and nonfoam-nesting species and exhibit a variety of sperm morphologies.
      Here, we examine the sperm morphology and motility of a foam-nesting
      Rhacophoridae frog, Polypedates leucomystax. Their spermatozoa have a sickle
      shaped head and a thick tail containing two axonemes with their doublet
      microtubule ones (Db1s) facing one another. These two axonemes are surrounded by
      hundreds of satellite microtubules that form a hexagonal lattice structure. The
      spermatozoa move spirally by directly converting their tail movements into
      propulsion force, similar to the movement of the sickle-shaped spermatozoa of
      Xenopus laevis. By comparing the spermatozoa of P. leucomystax to those of other
      foam-nesting Rhacophoridae frogs, Rhacophorus and Chiromantis, and to the nonfoam
      nesting Rhacophoridae frog, Buergeria buergeri, we found the following: (i)
      Spermatozoa of foam-nesting Rhacophoridae share common morphological features, a
      pair of axonemes and crystallized satellite microtubules. (ii) Spermatozoa of
      nonfoam-nesting Rhacophoridae do not exhibit these features. (iii) Sperm motility
      in foam-nesting Rhacophoridae is adapted to viscous environments. (iv) A
      diversity of sperm morphology and motility exists even among foam-nesting
      Rhacophoridae frogs. (v) The spermatozoa of Rhacophorus are more adapted to the
      foam nest than the spermatozoa of Polypedates.

PMID- 23125051
TI  - Optimization of a two-step process comprising lipase catalysis and thermal
      cyclization improves the efficiency of synthesis of six-membered cyclic carbonate
      from trimethylolpropane and dimethylcarbonate.
AB  - Six-membered cyclic carbonates are potential monomers for phosgene and/or
      isocyanate free polycarbonates and polyurethanes via ring-opening polymerization.
      A two-step process for their synthesis comprising lipase-catalyzed
      transesterification of a polyol, trimethylolpropane (TMP) with dimethylcarbonate
      (DMC) in a solvent-free system followed by thermal cyclization was optimized to
      improve process efficiency and selectivity. Using full factorial designed
      experiments and partial least squares (PLS) modeling for the reaction catalyzed
      by Novozym(r)435 (N435; immobilized Candida antarctica lipase B), the optimum
      conditions for obtaining either high proportion of monocarbonated TMP and TMP
      cyclic-carbonate (3 and 4), or dicarbonated TMP and monocarbonated TMP-cyclic
      carbonate (5 and 6) were found. The PLS model predicted that the reactions using
      15%-20% (w/w) N435 at DMC:TMP molar ratio of 10-30 can reach about 65% total
      yield of 3 and 4 within 10 h, and 65%-70% total yield of 5 and 6 within 32-37 h,
      respectively. High consistency between the predicted results and empirical data
      was shown with 66.1% yield of 3 and 4 at 7 h and 67.4% yield of 5 and 6 at 35 h,
      using 18% (w/w) biocatalyst and DMC:TMP molar ratio of 20. Thermal cyclization of
      the product from 7 h reaction, at 110 degrees C in the presence of acetonitrile
      increased the overall yield of cyclic carbonate 4 from about 2% to more than 75%
      within 24 h. N435 was reused for five consecutive batches, 10 h each, to give 3+4
      with a yield of about 65% in each run.

PMID- 23125052
TI  - Newer anticonvulsants: lamotrigine.

PMID- 23125053
TI  - Heinz A. Staab (1926-2012).

PMID- 23125054
TI  - Quantitative determination of magnetic force on a coronary stent in MRI.
AB  - PURPOSE: To introduce an analytical method for a quantitative determination of
      magnetic force on a coronary stent in the magnetic resonance imaging (MRI) magnet
      that is generally applicable to metallic implants. Magnetic forces on metallic
      implants in the MRI magnets are traditionally determined empirically by measuring
      deflection from the vertical plane at the central axis of the magnet and at the
      point of the largest force along the longitudinal axis of the magnet. MATERIALS
      AND METHODS: Magnetic and chemical characterization of the stents was performed
      by a commercial magnetometer and energy-dispersive X-ray spectroscopy. Magnetic
      force on the stents fabricated of paramagnetic alloys (surgical stainless steel
      and cobalt-chromium) was determined by measuring the stent's magnetic dipole
      moment and employing the on-axis magnetic field profile of an MRI magnet.
      RESULTS: The maximum force on the stainless steel stent was found to be F(S,max)
      = 0.18 mN, whereas on the cobalt-chromium stent it was F(C,max) = 0.06 mN.
      CONCLUSION: The magnetic force on the investigated paramagnetic stents is even
      smaller than the gravitational force acting on the stents in the Earth's gravity
      field, so that it has no physiological impact on the stented vessels.

PMID- 23125055
TI  - Microfluidic systems: a new toolbox for pluripotent stem cells.
AB  - Conventional culture systems are often limited in their ability to regulate the
      growth and differentiation of pluripotent stem cells. Microfluidic systems can
      overcome some of these limitations by providing defined growth conditions with
      user-controlled spatiotemporal cues. Microfluidic systems allow researchers to
      modulate pluripotent stem cell renewal and differentiation through biochemical
      and mechanical stimulation, as well as through microscale patterning and
      organization of cells and extracellular materials. Essentially, microfluidic
      tools are reducing the gap between in vitro cell culture environments and the
      complex and dynamic features of the in vivo stem cell niche. These microfluidic
      culture systems can also be integrated with microanalytical tools to assess the
      health and molecular status of pluripotent stem cells. The ability to control
      biochemical and mechanical input to cells, as well as rapidly and efficiently
      analyze the biological output from cells, will further our understanding of stem
      cells and help translate them into clinical use. This review provides a
      comprehensive insignt into the implications of microfluidics on pluripotent stem
      cell research.

PMID- 23125057
TI  - ELF exposure system for live cell imaging.
AB  - A programmable system has been developed for the study of both transient and
      persistent effects of extremely low frequency (ELF) magnetic field exposure of
      cell cultures. This high-precision exposure system enables experimental blinding
      and fully characterized exposure while simultaneously allowing live cell imaging.
      It is based on a live imaging cell around which two asymmetrical coils are wound
      in good thermal contact to a temperature-controlled water jacket, and is mounted
      on a microscope stage insert. The applied B-field uniformity of the active volume
      is better than 1.2% with an overall exposure uncertainty of less than 4.3% with
      very low transient field levels. The computer-controlled apparatus allows signal
      waveforms that are sinusoidal or composed of several harmonics, blind protocols,
      and monitoring of exposure and environmental conditions. B-fields up to 4 mT root
      mean square amplitude are possible with minimal temperature variation and no
      recognizable temperature differences between exposure and sham states. Sources of
      artifacts have been identified and quantified. There are no visible vibrations
      observable even at the highest magnifications and exposure levels.

PMID- 23125056
TI  - Unraveling sexual associations in contact and noncontact child sex offenders
      using the single category - implicit association test.
AB  - Previous studies found associations between children and sex in child sex
      offenders (CSOs) using the Implicit Association Test (IAT). We used a
      modification of this task, the Single Category-Implicit Association Test (SC-IAT)
      to unravel child-sex associations in CSOs. Using the SC-IAT, we were able to test
      whether CSOs indeed hold stronger child-sex associations relative to adult-sex
      associations, compared to adult sex offenders and nonoffenders. Furthermore, we
      examined whether contact CSOs differed from noncontact CSOs in their child-sex
      associations. The hypothesis that CSOs would have stronger child-sex
      associations, relative to their adult-sex associations, than adult sex offenders
      and nonoffenders was confirmed. No difference between contact CSOs and noncontact
      CSOs was found. Although the Sex SC-IAT was able to distinguish CSOs from
      nonoffenders, the sensitivity and specificity of the test was poor (AUC of .65)
      and needs refinement. The results of this study support the existence of a child
      sex association as a distinctive characteristic of CSOs. These findings are
      discussed in the context of theories on deviant cognitions in CSOs and risk for
      sexual offending. 

PMID- 23125058
TI  - Solution-processed fullerene-based organic Schottky junction devices for large
      open-circuit-voltage organic solar cells.
AB  - A solution-processed fullerene-based organic Schottky junction photovoltaic
      device is fabricated to produce a large open circuit voltage, 0.85-0.95 V, which
      is higher than that of most organic bulk-heterojunction devices. A power
      conversion efficiency of 5% is achieved in fullerene-derivative [6,6]-phenyl-C71
      butyric acid methylester-based Schottky junction devices.

PMID- 23125059
TI  - Simultaneous analysis of small organic acids and humic acids using high
      performance size exclusion chromatography.
AB  - An accurate and fast method for simultaneous determination of small organic acids
      and much larger humic acids was developed using high performance size exclusion
      chromatography. Two small organic acids, i.e. salicylic acid and 2,3
      dihydroxybenzoic acid, and one purified humic acid material were used in this
      study. Under the experimental conditions, the UV peaks of salicylic acid and 2,3
      dihydroxybenzoic acid were well separated from the peaks of humic acid in the
      chromatogram. Concentrations of the two small organic acids could be accurately
      determined from their peak areas. The concentration of humic acid in the mixture
      could then be derived from mass balance calculations. The measured results agreed
      well with the nominal concentrations. The detection limits are 0.05 mg/L and 0.01
      mg/L for salicylic acid and 2,3-dihydroxybenzoic acid, respectively.
      Applicability of the method to natural samples was tested using groundwater,
      glacier, and river water samples (both original and spiked with salicylic acid
      and 2,3-dihydroxybenzoic acid) with a total organic carbon concentration ranging
      from 2.1 to 179.5 mg C/L. The results obtained are promising, especially for
      groundwater samples and river water samples with a total organic carbon
      concentration below 9 mg C/L.

PMID- 23125060
TI  - Osteogenic differentiation and osteochondral tissue engineering using human
      adipose-derived stem cells.
AB  - Osteogenesis and the production of composite osteochondral tissues were
      investigated using human adult adipose-derived stem cells and polyglycolic acid
      (PGA) mesh scaffolds under dynamic culture conditions. For osteogenesis, cells
      were expanded with or without osteoinduction factors and cultured in control or
      osteogenic medium for 2 weeks. Osteogenic medium enhanced osteopontin and
      osteocalcin gene expression when applied after but not during cell expansion.
      Osteogenesis was induced and mineralized deposits were present in tissues
      produced using PGA culture in osteogenic medium. For development of osteochondral
      constructs, scaffolds seeded with stem cells were precultured in either
      chondrogenic or osteogenic medium, sutured together, and cultured in dual-chamber
      stirred bioreactors containing chondrogenic and osteogenic media in separate
      compartments. After 2 weeks, total collagen synthesis was 2.1-fold greater in the
      chondroinduced sections of the composite tissues compared with the osteoinduced
      sections; differentiation markers for cartilage and bone were produced in both
      sections of the constructs. The results from the dual-chamber bioreactor
      highlight the challenges associated with achieving simultaneous chondrogenic and
      osteogenic differentiation in tissue engineering applications using a single stem
      cell source.

PMID- 23125061
TI  - Epidemiological analysis of retinopathy of prematurity in a referral centre in
      Turkey.
AB  - PURPOSE: To collect data towards the establishment of a guideline to predict the
      population under risk for the development of retinopathy of prematurity (ROP) in
      Turkey. METHODS: Medical reports of 2950 preterm infants who underwent screening
      examinations for ROP between 1996 and 2010 at Istanbul Faculty of Medicine,
      Department of Ophthalmology were reviewed. The study population was classified as
      inpatient infants and referred infants. A risk factor analysis was performed
      limited to the 788 inpatient infants. The demographical variables regarding birth
      weight (BW), gestational age (GA) and postnatal age at the time of treatment were
      compared independently between 403 referred and 64 inpatient infants who were
      treated for severe ROP. RESULTS: The mean GA of the infants with severe ROP was
      31.2+/-2.7 weeks, mean BW was 1543.4+/-508.3 g. The risk factor analysis of
      inpatient infants revealed BW<1500 g, GA<32 weeks; intraventricular haemorrhage,
      respiratory distress syndrome, sepsis, apnoea and phototherapy were associated
      with a higher incidence of ROP. In addition, sepsis, male gender, multiple
      gestations, BW<1500 g were associated with a higher incidence of progression to
      severe ROP, whereas maternal pre-eclampsia was associated with a lower incidence.
      On the other hand, comparison of demographic features revealed that the referred
      infants with ROP were born at a significantly higher BW and needed significantly
      earlier treatment than inpatient infants with ROP. CONCLUSIONS: The high BW and
      GA of infants with severe ROP indicate wider screening criteria should be used in
      our country. BW might be a more important criterion than GA for ROP screening.

PMID- 23125062
TI  - Lacrimal sac mucocele.

PMID- 23125063
TI  - Mitomycin-augmented non-penetrating deep sclerectomy: preoperative gonioscopy and
      postoperative perimetric, tonometric and medication trends.
AB  - BACKGROUND/AIMS: Non-penetrating deep sclerectomy (NPDS) can enhance drainage of
      aqueous humour without disrupting the trabecular endothelial layer, reducing
      risks of postoperative hypotony and hyphema. This study explores associations of
      angle morphology with surgical efficacy in eyes with open and obstructed angles.
      METHODS: Eighty-nine consecutive eyes undergoing successful NPDS (non-implant,
      with 0.4 mg/ml mitomycin C and limbus-based two-layer closure) were studied in
      this institutional review board-approved retrospective quality assurance study.
      Postoperative complication frequency, intraocular pressure (IOP), glaucoma
      medications required and acuity were monitored (baseline vs 3, 6, 9, 12 and 18
      month postoperative levels), along with 30-2 Humphrey MD and corrected pattern
      standard deviation (CPSD) (baseline vs 6, 12 and 18-month postoperative values).
      Preoperative gonioscopy was compared with the subsequent requirement for specific
      postoperative interventions. RESULTS: IOP at all five postoperative intervals was
      reduced (22 +/- 0.9 to 12 +/- 0.5 mm Hg; p<0.0001). No hyphema were observed.
      Postoperative hypotony (IOP < 4 mm Hg) occurred rarely (8/445; 1.8%). Mean
      glaucoma medication use dropped from 3.1 +/- 0.1 to 0.23 +/- 0.1 at 18 months
      (p<0.0001). Mean 30-2 MD improved by approximately 1.4 dB at 6, 12 and 18 months
      (p<0.002); CPSD remained stable. CONCLUSIONS: Following NPDS, a sustained IOP
      decrease of 10 mm Hg (45%) was attained, with stable acuity, increased perimetric
      generalised light sensitivity and 90% reduction in medical therapy requirement.
      Morbidity risk was associated with narrow gonioscopic angle insertion and
      synechia, but not with shallow approach or trabecular pigmentation.

PMID- 23125064
TI  - Retinal mosaicism in a girl with an X-Y translocation.

PMID- 23125065
TI  - Position of the central retinal vessel trunk and pattern of remaining visual
      field in advanced glaucoma.
AB  - BACKGROUND: To investigate the association between the position of the central
      retinal vessel trunk (CRVT) in the optic nerve head and the pattern of remaining
      visual field and thickness of the retinal nerve fibre layer (RNFL) in end-stage
      glaucoma. METHODS: The clinical observational study included patients with end
      stage glaucoma with a remaining central visual field island (CI-group) or
      temporal visual field remnant (TI-group). The position of the CRVT exit on the
      lamina cribrosa was evaluated on optic disc photographs. The RNFL thickness was
      measured by optical coherence tomography. RESULTS: The study included 21 glaucoma
      patients with a remaining central visual field island and 22 glaucoma patients
      with a temporal visual field remnant. Both groups did not differ significantly in
      age, gender, refractive error, central corneal thickness, axial length and mean
      RNFL thickness. RNFL in the temporal region (48.1+/-5.5 MUm vs 37.2+/-7.9 MUm;
      p<0.001) was significantly thicker, and RNFL in the nasal region (41.6+/-8.3 MUm
      vs 48.0+/-7.8 MUm; p=0.01) was significantly thinner in the CI-group than TI
      group. The CRVT was located in the temporal disc part significantly more often in
      the CI-group than in the TI-group (6/21 vs 0/22; p=0.009). The distance from the
      CRVT to the temporal disc border expressed as percentage of total disc diameter
      was significantly smaller in the CI-group than in the TI-group(0.55+/-0.07 vs
      0.79+/-0.08; p<0.001). CONCLUSIONS: The pattern of perimetric loss was associated
      with the CRVT position: eyes with a central visual field island tended to have
      the CRVT in the temporal optic disc region.

PMID- 23125066
TI  - A novel photoaffinity-based probe for selective detection of cathepsin L active
      form.
AB  - Detecting the active forms of proteases by using activity-based probes in complex
      proteomes has become an intensively investigated field of research over the past
      years because many pathogenic conditions involve alterations in protease
      activities. The detection of lysosomal cysteine proteases, the cathepsins, has
      mostly relied on the use of probes that incorporate reactive electrophilic
      moieties to modify a cysteine in the active site covalently. Here we report the
      first example of an activity-based probe that targets the cathepsins and
      incorporates a photoactivatable benzophenone group for covalent labelling. When
      tested on a set of five cathepsins (B, K, L, S and V), this probe selectively
      labelled the active site of cathepsin L. Furthermore, when tested on crude cell
      extracts, the probe specifically detected cathepsin L quantities as low as a few
      picomoles. This study suggests that photoaffinity labelling is a promising
      approach for developing highly selective and useful cathepsin L probes. In
      particular, this probe might allow the detection of small amounts of the secreted
      active cathepsin L form in the cellular microenvironment in vitro and ex vivo.

PMID- 23125067
TI  - Characterization of the cardiac response to a low and high dose of dobutamine in
      the mouse model of dilated cardiomyopathy by MRI in vivo.
AB  - PURPOSE: To assess the cardiac response to low (0.15-0.5 mg/kg i.p.) and high
      (1.5-20 mg/kg i.p.) doses of dobutamine in Tgalphaq*44 mice with dilated
      cardiomyopathy at the stage of advanced heart failure. MATERIALS AND METHODS:
      Inotropic, lusitropic, and chronotropic response to beta(1) -adrenergic
      stimulation was assessed by the cine magnetic resonance imaging (MRI) protocol
      based on the electrocardiogram (ECG)-triggered bright-blood images of one
      midventricular short-axis slice. RESULTS: In wildtype mice increasing doses of
      dobutamine resulted in subsequent increase in the left ventricular function and
      heart rate acceleration, but significant inotropic, lusitropic, and chronotropic
      cardiac response was observed only after high doses of dobutamine, what is
      typical. In the Tgalphaq*44 mice low doses of dobutamine significantly increased
      inotropic and lusitropic cardiac performance without chronotropic changes. An
      increased heart rate was observed only after high doses of dobutamine, but then
      inotropic and lusitropic cardiac functional reserve was lost. CONCLUSION: We
      described MRI stress test protocol based on a low and high dose of dobutamine
      induced response that proves useful in revealing alternation in cardiac function
      in mice with heart failure.

PMID- 23125068
TI  - Visualization of latent fingermarks by nanotechnology: reversed development on
      paper--a remedy to the variation in sweat composition.

PMID- 23125069
TI  - Comment on changes in sex ratio in neural tube defects since food fortification
      with folic acid: re "hypothesis: the female excess in cranial neural tube defects
      reflects an epigenetic drag of the inactivating X chromosome on the molecular
      mechanisms of neural tube fold elevation".

PMID- 23125070
TI  - Contribution of Leydig and Sertoli cells to testosterone production in mouse
      fetal testes.
AB  - Testosterone is a final product of androgenic hormone biosynthesis, and Leydig
      cells are known to be the primary source of androgens. In the mammalian testis,
      two distinct populations of Leydig cells, the fetal and the adult Leydig cells,
      develop sequentially, and these two cell types differ both morphologically and
      functionally. It is well known that the adult Leydig cells maintain male
      reproductive function by producing testosterone. However, it has been
      controversial whether fetal Leydig cells can produce testosterone, and the
      synthetic pathway of testosterone in the fetal testis is not fully understood. In
      the present study, we generated transgenic mice in which enhanced green
      fluorescence protein was expressed under the control of a fetal Leydig cell
      specific enhancer of the Ad4BP/SF-1 (Nr5a1) gene. The transgene construct was
      prepared by mutating the LIM homeodomain transcription factor (LHX9)-binding
      sequence in the promoter, which abolished promoter activity in the
      undifferentiated testicular cells. These transgenic mice were used to collect
      highly pure fetal Leydig cells. Gene expression and steroidogenic enzyme
      activities in the fetal Leydig cells as well as in the fetal Sertoli cells and
      adult Leydig cells were analyzed. Our results revealed that the fetal Leydig
      cells synthesize only androstenedione because they lack expression of Hsd17b3,
      and fetal Sertoli cells convert androstenedione to testosterone, whereas adult
      Leydig cells synthesize testosterone by themselves. The current study
      demonstrated that both Leydig and Sertoli cells are required for testosterone
      synthesis in the mouse fetal testis.

PMID- 23125071
TI  - Arteriovenous malformations and other vascular malformation syndromes.
AB  - Vascular malformations are a disruption of the normal vascular pattern in which
      it is expected that a capillary network of microscopic vessels lies interposed
      between high-pressure arteries that deliver blood and thin-walled veins that
      collect low-pressure blood for return to the heart. In the case of arteriovenous
      malformations, arteries or arterioles connect directly to the venous collection
      system, bypassing any capillary bed. Clinical consequences result from rupture
      and hemorrhage, from dramatically increased blood flow, or from the loss of
      capillary functions such as nutrient exchange and filtering function. These
      malformations can occur sporadically or as a component of inherited vascular
      malformation syndromes. In these and other hereditary vascular malformation
      syndromes, genetic studies have identified proteins and pathways involved in
      vascular morphogenesis and development. A common theme observed is that vascular
      malformations result from disruption in pathways involved in vascular stability.
      Here we review the vascular malformations and pathways involved in hereditary
      hemorrhagic telangiectasia, capillary malformation-arteriovenous malformation,
      cerebral cavernous malformations, and mucocutaneous venous malformations.

PMID- 23125072
TI  - Medications development for opioid abuse.
AB  - Here we describe methods for preclinical evaluation of candidate medications to
      treat opioid abuse and dependence. Our perspective is founded on the propositions
      that (1) drug self-administration procedures provide the most direct method for
      assessment of medication effects, (2) procedures that assess choice between
      opioid and nondrug reinforcers are especially useful, and (3) the states of
      opioid dependence and withdrawal profoundly influence both opioid reinforcement
      and the effects of candidate medications. Effects of opioid medications on opioid
      choice in nondependent and opioid-dependent subjects are reviewed. Various
      nonopioid medications have also been examined, but none yet have been identified
      that safely and reliably reduce opioid choice. Future research will focus on (1)
      strategies for increasing safety and/or effectiveness of opioid medications, and
      (2) continued development of nonopioids such as inhibitors of endocannabinoid
      catabolic enzymes or inhibitors of opioid-induced glial activation.

PMID- 23125074
TI  - MAGE-A10 cancer/testis antigen is highly expressed in high-grade non-muscle
      invasive bladder carcinomas.
AB  - Bladder cancer is a common urinary malignancy and a prevalent cause of cancer
      related death. Current therapies of early stage non-muscle-invasive bladder
      cancer (NMIBC) are frequently associated with undesirable toxicities and
      recurrence. Active antigen-specific immunotherapy may provide a valid therapeutic
      option for patients with NMIBC. Cancer-testis antigens (CTA) expressed in various
      tumour types and in a limited range of healthy tissues may represent potential
      targets for specific immunotherapy. MAGE-A10 is probably the most immunogenic
      antigen of the MAGE-A family. We evaluated the expression of MAGE-A10 in NMIBC.
      Seventy-nine patients undergoing surgical treatment for NMIBC were enrolled in
      the study. MAGE-A10 gene expression was assessed by quantitative real-time
      polymerase chain reaction. Immunohistochemistry was performed on paraffin
      embedded sections. MAGE-A10 gene was specifically expressed in one-third of NMIBC
      (n = 24: 32.43%). Gene expression was correlated with high tumour grade. MAGE-A10
      protein was exclusively detectable in nuclei of tumour cells. More importantly,
      MAGE-A10 protein was also more frequently detectable in high-grade tumours (p =
      0.0001) and in stage T1 tumours invading subepithelial tissue or lamina propria
      (p = 0.01). A strong correlation between MAGE-A10 staining score and tumour grade
      and stage could accordingly be observed. These data indicate that MAGE-A10
      expression is a feature of aggressive NMIBC and might be used as a novel target
      for specific immunotherapy of these cancers.

PMID- 23125073
TI  - Diabetes in Kyrgyzstan: changes between 2002 and 2009.
AB  - Health system reform in Kyrgyzstan is seen as a relative success story in central
      Asia. Initially, most attention focused on structural changes, and it is only
      since 2006 that the delivery of care and the experience of health service users
      have risen on the agenda. One exception from the earlier period was a rapid
      appraisal of the management of diabetes, undertaken in 2002. Using that study as
      a baseline, we describe the findings of a new evaluation of diabetes management,
      undertaken in 2009, using the Rapid Assessment Protocol for Insulin Access, now
      implemented in seven countries. Access to care has improved through the creation
      of the Family Medical Centres and the deployment of endocrinologists to them.
      Another improvement is the access to insulin and related medicines, although
      assessment of the procurement system reveals that the government is getting very
      poor value for money. Looking ahead, there are grounds for optimism that the
      passage of the law on diabetes may progressively have a greater impact. Although
      the law is not yet fully implemented, it has enabled the diabetes associations to
      defend the rights of their members. This increased capacity is credited with some
      improvements in diabetes care.

PMID- 23125075
TI  - Engaging consumers in medicaid nursing home reimbursement policy: lessons from
      New York and Minnesota.
AB  - PURPOSE OF THE STUDY: This study draws lessons for successful consumer engagement
      in Medicaid nursing home (NH) reimbursement policy from New York and Minnesota.
      In these two states, resident advocates have influenced reimbursement policy to
      better encourage access, care quality, and quality of life. DESIGN AND METHODS:
      Twenty-four semi-structured interviews were conducted, including consumer
      advocates, state agency officials, legislators/legislative staff, and NH industry
      representatives. Transcripts were coded to identify recurring themes and patterns
      in responses. Related documents were reviewed as well. FINDINGS: Interviewees
      report that consumer advocates should participate in NH reimbursement policy
      making to provide a unique perspective distinct from other stakeholder groups.
      Skills necessary for successful participation include developing, demonstrating,
      and sharing expertise to gain credibility as a legitimate actor. Effective
      strategies include participating on state workgroups and taskforces and
      developing and accessing relationships with key legislative and executive branch
      officials. A division of labor may be useful with those consumer advocates
      possessing expertise in NH reimbursement policy partnering with other
      organizations with the experience and resources necessary to marshal grassroots
      support. IMPLICATIONS: State and federal reimbursement reform provide
      opportunities for consumer advocacy influence during the design and
      implementation process. The experience of consumer groups in New York and
      Minnesota provide lessons for advocates looking to influence these and other
      reimbursement initiatives.

PMID- 23125076
TI  - Current strategies in antibody engineering: Fc engineering and pH-dependent
      antigen binding, bispecific antibodies and antibody drug conjugates.
AB  - Antibody engineering technologies are constantly advancing to improve the
      clinical effectiveness of monoclonal antibodies (mAbs). Effector functions may be
      modified by engineering the Fc region, for example to improve or reduce binding
      to Fc gamma receptors (FcgammaRs) or complement factors. Other examples for Fc
      engineering include modification of the half-life of immunoglobulin G (IgG);
      various studies have shown that half-life can be prolonged by increasing the
      affinity of Fc for the Fc neonatal receptor (FcRn). Furthermore, engineered pH
      dependent antigen binding can be applied to enhance the recycling of IgG via
      FcRn, enabling binding to additional target molecules. Since bispecific
      approaches may elicit desired effects on disease targets, a variety of bispecific
      formats have been developed, including variants that structurally mimic IgG.
      Finally, antibody-drug conjugates (ADCs) create new opportunities for treatment
      of certain diseases. Advances in antibody generation, selection of highly
      cytotoxic molecules and production of stable linkers have paved the way to the
      development of many ADCs that can be tested in clinical trials. This review
      covers current antibody engineering strategies for the modification of
      therapeutic antibodies in the areas of Fc engineering and pH-dependent antigen
      binding, bispecific antibodies and ADCs.

PMID- 23125077
TI  - Layer-by-layer-assembled reduced graphene oxide/gold nanoparticle hybrid double
      floating-gate structure for low-voltage flexible flash memory.

PMID- 23125078
TI  - Nkx2-1: a novel tumor biomarker of lung cancer.
AB  - Nkx2-1 (Nkx homeobox-1 gene), also known as TTF-1 (thyroid transcription factor
      1), is a tissue-specific transcription factor of the thyroid, lung, and ventral
      forebrain. While it has been shown to play a critical role in lung development
      and lung cancer differentiation and morphogenesis, molecular mechanisms mediating
      Nkx2-1 cell- and tissue-specific expression in normal and cancerous lungs have
      yet to be fully elucidated. The recent identification of prognostic biomarkers in
      lung cancer, particularly in lung adenocarcinoma (ADC), and the different
      reactivity of patients to chemotherapeutic drugs have opened new avenues for
      evaluating patient survival and the development of novel effective therapeutic
      strategies. The function of Nkx2-1 as a proto-oncogene was recently characterized
      and the gene is implicated as a contributory factor in lung cancer development.
      In this review, we summarize the role of this transcription factor in the
      development, diagnosis, and prognosis of lung cancer in the hope of providing
      insights into the utility of Nkx2-1 as a novel biomarker of lung cancer.

PMID- 23125079
TI  - Tetrandrine citrate eliminates imatinib-resistant chronic myeloid leukemia cells
      in vitro and in vivo by inhibiting Bcr-Abl/beta-catenin axis.
AB  - OBJECTIVE: To evaluate the effects of tetrandrine citrate, a novel tetrandrine
      salt with high water solubility, on the growth of imatinib (IM)-resistant chronic
      myeloid leukemia (CML) in vitro and in vivo, and reveal action molecular
      mechanisms. METHODS: Cell viability in vitro was measured using methyl thiazolyl
      tetrazolium (MTT) assay. CML cell growth in vivo was assessed using a xenograft
      model in nude mice. Bcr-Abl and beta-catenin protein levels were determined using
      Western blotting. Bcr-Abl messenger RNA (mRNA) was measured by reverse
      transcription polymerase chain reaction (RT-PCR). Flow cytometry (FCM) was used
      to determine cell cycle status. RESULTS: Tetrandrine citrate inhibited the growth
      of IM-resistant K562 cells, primary leukemia cells, and primitive CD34(+)
      leukemia cells, and their inhibition concentration that inhibited 50% of target
      cells (IC(50)) ranged from 1.20 to 2.97 MUg/ml. In contrast, tetrandrine citrate
      did not affect normal blood cells under the same conditions, and IC(50) values
      were about 10.12-13.11 MUg/ml. Oral administration of tetrandrine citrate caused
      complete regression of IM-resistant K562 xenografts in nude mice without overt
      toxicity. Western blot results revealed that treatment of IM-resistant K562 cells
      with tetrandrine citrate resulted in a significant decrease of both p210(Bcr-Abl)
      and beta-catenin proteins, but IM did not affect the Bcr-Abl protein levels.
      Proteasome inhibitor, MG132, did not prevent tetrandrine-mediated decrease of the
      p210(Bcr-Abl) protein. RT-PCR results showed that tetrandrine treatment caused a
      decrease of Bcr-Abl mRNA. FCM analysis indicated that tetrandrine induced gap 1
      (G(1)) arrest in CML cells. CONCLUSIONS: Tetrandrine citrate is a novel orally
      active tetrandrine salt with potent anti-tumor activity against IM-resistant K562
      cells and CML cells. Tetrandrine citrate-induced growth inhibition of leukemia
      cells may be involved in the depletion of p210(Bcr-Abl) mRNA and beta-catenin
      protein.

PMID- 23125080
TI  - XRCC1 Arg399Gln and clinical outcome of platinum-based treatment for advanced non
      small cell lung cancer: a meta-analysis in 17 studies.
AB  - OBJECTIVE: XRCC1 polymorphism is a research hotpot in individual treatment for
      non-small cell lung cancer (NSCLC). To obtain the association between XRCC1
      polymorphism and clinical outcome of platinum-based treatment for NSCLC, a meta
      analysis was conducted. METHODS: Databases including PubMed, Embase, Cochrane,
      and Chinese National Knowledge Infrastructure (CNKI) were searched for
      publications that met the inclusion criteria. A fixed effect model was used to
      estimate pooled odds ratio (OR) and hazard ratio (HR) with 95% confidence
      interval (CI) for the association between XRCC1 Arg399Gln and response or
      survival of platinum-based treatment for advanced NSCLC. A chi-squared-based Q
      test was used to test the heterogeneity hypothesis. Egger's test was used to
      check publication bias. RESULTS: Seventeen published case-control studies that
      focus on the association between XRCC1 Arg399Gln and response or survival of
      platinum-based treatment for advanced NSCLC in 2256 subjects were included in
      this meta-analysis, of whom 522 were AA genotypes (23.2% frequency), 916 AG
      genotypes (40.6% frequency), and 818 GG genotypes (36.2% frequency). The overall
      response rate (ORR) was 45.2% (110/243) for AA genotype patients, 29.9% for AG
      genotype (73/244), and 30.7% for GG genotype (124/403). The heterogeneity test
      did not show any heterogeneity and the Egger's test did not reveal an obvious
      publication bias among the included studies. The meta-analysis indicated that AA
      genotype patients presented higher response rates toward platinum drug treatment
      compared with G model (GG+GA) patients (GG vs. AA model: OR=0.489, 95% CI 0.266
      0.900, P=0.021; AG vs. AA model: OR=0.608, 95% CI 0.392-0.941, P=0.026; GA+AA vs.
      GG model: OR=1.259, 95% CI 0.931-1.701, P=0.135; GG+GA vs. AA model: OR=0.455,
      95% CI 0.313-0.663, P=0.0001). However, no evidence validates XRCC1 associates
      with the survival following platinum drug therapy. CONCLUSIONS: Our meta-analysis
      suggested that XRCC1 Arg399Gln is related with the sensitivity of NSCLC patients
      to platinum-based treatment. AA genotype patients present more desirable curative
      effectiveness compared with other patients.

PMID- 23125081
TI  - ST13, a proliferation regulator, inhibits growth and migration of colorectal
      cancer cell lines.
AB  - BACKGROUND AND OBJECTIVE: ST13, is the gene encoding the HSP70 interacting
      protein (HIP). Previous research has shown that ST13 mRNA and protein levels are
      down-regulated in colorectal cancer (CRC) tissues compared with adjacent normal
      tissues. This study aims at the role of ST13 in the proliferation and migration
      of CRC cells. METHODS: The transcript level of ST13 in different CRC cell lines
      was evaluated by quantitative reverse transcriptase-polymerase chain reaction
      (qRT-PCR). ST13-overexpressed and ST13-knockdown CRC cells were constructed
      respectively by lentiviral transduction, followed by 3-[4,5-dimethylthiazol-2-yl]
      2,5-diphenyl tetrazolium bromide (MTT) assay, plate colony formation, cell-cycle
      analysis, and migration assays to evaluate the influence of ST13 on proliferation
      and migration in vitro. Moreover, a mouse xenograft study was performed to test
      in vivo tumorigenicity of ST13-knockdown CRC cells. RESULTS: Lentivirus-mediated
      overexpression of ST13 in CRC cells inhibited cell proliferation, colony
      formation, and cell migration in vitro. In contrast, down-regulation of ST13 by
      lentiviral-based short hairpin RNA (shRNA) interference in CRC cells
      significantly increased cell proliferation and cloning efficiency in vitro. In
      addition, down-regulation of ST13 expression significantly increased the
      tumorigenicity of CRC cells in vivo. CONCLUSIONS: ST13 gene is a proliferation
      regulator that inhibits tumor growth in CRC and may affect cell migration.

PMID- 23125082
TI  - Influence of gonadotropin-releasing hormone agonist on the effect of chemotherapy
      upon ovarian cancer and the prevention of chemotherapy-induced ovarian damage: an
      experimental study with nu/nu athymic mice.
AB  - BACKGROUND AND OBJECTIVE: Gonadotropin-releasing hormone (GnRH) plays an
      important role in the regulation of ovarian function and ovarian cancer cell
      growth. In this study, we determined whether administration of the GnRH agonist
      (GnRHa), triporelin, prior to cisplatin treatment affects cisplatin and/or
      prevents cisplatin-induced ovarian damage. METHODS: nu/nu mice were injected with
      ovarian cancer OVCAR-3 cells intraperitoneally. After two weeks, the mice were
      treated with saline (control), cisplatin, GnRHa, or cisplatin plus GnRHa for four
      weeks. At the end of the experimental protocol, blood, tumor, ovary, and uterine
      tissues were resected for hematoxylin and eosin (H&E) staining,
      immunohistochemical analyses of Ki67, nuclear factor-kappaB (NF-kappaB), and
      caspase-3, transmission electron microscopy of apoptosis, or enzyme-linked
      immunosorbent assay (ELISA) analyses of anti-Mullerian hormone (AMH). RESULTS:
      Cisplatin treatment effectively inhibited tumor growth in mice treated with human
      ovarian cancer cells; however the treatment also induced considerable toxicity.
      Immunohistochemical analyses showed that Ki67 expression was reduced in cisplatin
      treated mice compared to control (P<0.05), but there was no statistically
      significant differences between cisplatin-treated mice and cisplatin plus GnRHa
      treated mice (P>0.05), while expressions of NF-kappaB and caspase-3 were reduced
      and induced, respectively, in cisplatin-treated mice and cisplatin plus GnRHa
      treated mice. Apoptosis occurred in the GnRHa, cisplatin, and cisplatin plus
      GnRHa-treated mice, but not in control mice. Ovaries exposed to GnRHa in both
      GnRHa mice and cisplatin-treated mice (combination group) had significantly more
      primordial and growth follicles and serum levels of AMH than those in the control
      mice and cisplatin-treated mice (P<0.05). CONCLUSIONS: Administration of GnRHa to
      mice significantly decreased the extent of ovarian damage induced by cisplatin,
      but did not affect the anti-tumor activity of cisplatin.

PMID- 23125083
TI  - Comparison of the effects of acute and chronic psychological stress on metabolic
      features in rats.
AB  - This study was aimed to compare the effects of acute and chronic psychological
      stress on metabolic factors. Forty-two male Wistar rats were divided into control
      and stressed groups. Stress was applied by a communication box acutely (1 d) and
      chronically (15 and 30 d). Blood sampling was carried out by retro-orbital
      puncture method. The plasma levels of glucose, cholesterol, triglyceride,
      insulin, and corticosterone were measured. In addition, feed and water intake,
      latency to eat and drink, adrenal and body weights were determined. Acute and
      chronic psychological stress did not significantly change basal plasma
      corticosterone levels. However, immediately (1 min) after acute exposure to
      stress, plasma corticosterone level increased compared to that before stress
      exposure. Acute stress increased plasma insulin levels significantly. Fifteen
      days of stress exposure resulted in plasma glucose increase. Chronic stress
      significantly increased feed intake, latency to eat, and adrenal weight compared
      to acute stress. The body weights of both control and stressed groups increased
      markedly during the experiment. Homeostasis model assessment of insulin
      resistance (HOMA-IR) index did not change significantly in the stressed group. In
      conclusion, application of acute and chronic psychological stress leads to
      different metabolic and/or behavioral changes but the metabolic changes resulting
      from acute exposure to stress seem to be more pronounced.

PMID- 23125084
TI  - DEL RBC transfusion should be avoided in particular blood recipient in East Asia
      due to allosensitization and ineffectiveness.
AB  - Previously, both primary and secondary anti-D alloimmunizations induced by "Asian
      type" DEL (RHD1227A allele) were observed in two incidents. We investigated how
      often these alloimmunization events occur. The transfusions of any D-negative
      patients were investigated in the First Affiliated Hospital of Xi'an Jiaotong
      University Medical College, China, during the entire 2009. The antigens of D, C,
      c, E, and e were routinely serotyped. The "Asian type" DEL variant was genotyped
      and the RHD heterozygote was determined through two published methods. The
      changes in anti-D levels were monitored by the indirect antiglobulin test (IAT)
      and flow cytometry. Thirty D-negative transfused patients were included in the
      study. We focused on 11 recipients who were transfused with packed red blood
      cells (RBCs) from DEL donors at least one time. Of those 11 recipients, seven
      were anti-D negative before transfusion and four were anti-D positive (one
      patient with an autoantibody). One of the seven pre-transfusion anti-D negative
      patients produced a primary-response anti-D after being transfused with 400 ml of
      DEL blood twice. All four pre-transfusion antibody positive patients were not
      observed hemoglobin (Hb) levels increased, as expected after transfusions. Two
      patients had an increase in anti-D from 1:8 to 1:64 by IAT, which was also shown
      by flow cytometry. None of the patients experienced an acute hemolytic episode.
      Our data indicated that the primary anti-D induced by DEL transfusion or the
      secondary anti-D elevated by DEL in a truly D-negative patient might not be
      unusual. We suggest that a truly D-negative childbearing-aged woman should avoid
      DEL transfusion to protect her from primary anti-D allosensitization. In
      addition, anti-D positive recipients should also avoid DEL red cell transfusion
      due to the delayed hemolytic transfusion reaction (DHTR).

PMID- 23125086
TI  - Propolis modulates vitronectin, laminin, and heparan sulfate/heparin expression
      during experimental burn healing.
AB  - OBJECTIVE: This study was aimed at assessing the dynamics of vitronectin (VN),
      laminin (LN), and heparan sulfate/heparin (HS/HP) content changes during
      experimental burn healing. METHODS: VN, LN, and HS/HP were isolated and purified
      from normal and injured skin of domestic pigs, on the 3rd, 5th, 10th, 15th, and
      21st days following thermal damage. The wounds were treated with apitherapeutic
      agent (propolis), silver sulfadiazine (SSD), physiological salt solution, and
      propolis vehicle. VN and LN were quantified using an immunoenzymatic assay and
      HS/HP was estimated by densitometric analysis. RESULTS: Propolis treatment
      stimulated significant increases in VN, LN, and HS/HP contents during the initial
      phase of study, followed by a reduction in the estimated extracellular matrix
      molecules. Similar patterns, although less extreme, were observed after treatment
      with SSD. CONCLUSIONS: The beneficial effects of propolis on experimental wounds
      make it a potential apitherapeutic agent in topical burn management.

PMID- 23125087
TI  - Establishment of reference mandibular plane for anterior alveolar morphology
      evaluation using cone beam computed tomography.
AB  - To propose a method of establishing the reference mandibular plane (MP), which
      could be reestablished according to the coordinates of the reference points, and
      then facilitate the assessment of anterior alveolar morphology using cone beam
      computed tomography (CBCT), sixty patients with bimaxillary protrusion were
      randomly selected and CBCT scans were taken. The CBCT scans were transferred to
      Materialism's interactive medical image control system 10.01 (MIMICS 10.01), and
      three dimensional models of the entire jaws were constructed. Reference points
      determining the reference MP were positioned in the coronal, axial, sagittal
      windows, and the points were exactly located by recording their coordinates in
      the interfaces of software. The reference MP provided high intra-observer
      reliability (Pearson's r 0.992 to 0.999), and inter-observer reliability (intra
      class correlation coefficients (ICCs) 0.996 to 0.999).

PMID- 23125085
TI  - Effects of dexamethasone and Salvia miltiorrhiza on multiple organs in rats with
      severe acute pancreatitis.
AB  - OBJECTIVE: To investigate the protective effects and mechanisms of action of
      dexamethasone and Salvia miltiorrhiza on multiple organs in rats with severe
      acute pancreatitis (SAP). METHODS: The rats were divided into sham-operated,
      model control, dexamethasone treated, and Salvia miltiorrhiza treated groups. At
      3, 6, and 12 h after operation, the mortality rate of different groups,
      pathological changes, Bcl-2-associated X protein (Bax) and nuclear factor-kappaB
      (NF-kappaB) protein expression levels in multiple organs (the pancreas, liver,
      kidneys, and lungs), toll-like receptor 4 (TLR-4) protein levels (only in the
      liver), intercellular adhesion molecule 1 (ICAM-1) protein levels (only in the
      lung), and terminal deoxynucleotidy transferase mediated deoxyuridine
      triphosphate (dUTP) nick end labeling (TUNEL) staining expression levels, as well
      as the serum contents of amylase, glutamate-pyruvate transaminase (GPT), glutamic
      oxaloacetic transaminase (GOT), blood urea nitrogen (BUN), and creatinine (CREA)
      were observed. RESULTS: The mortality rate of the dexamethasone treated group was
      significantly lower than that of the model control group (P<0.05). The
      pathological changes in multiple organs in the two treated groups were relieved
      to different degrees (P<0.05 and P<0.01, respectively), the expression levels of
      Bax and NF-kappaB proteins, and apoptotic indexes of multiple organs were reduced
      (P<0.05 and P<0.01, respectively). The contents of amylase, GPT, GOT, BUN, and
      CREA in the two treated groups were significantly lower than those in model
      control groups (P<0.05 and P<0.01, respectively). The expression level of ICAM-1
      protein in the lungs (at 3 and 12 h) in the dexamethasone treated group was
      significantly lower than that in the Salvia miltiorrhiza treated group (P<0.05).
      The serum contents of CREA (at 12 h) and BUN (at 6 h) of the Salvia miltiorrhiza
      treated group were significantly lower than those in the dexamethasone treated
      group (P<0.05). CONCLUSIONS: Both dexamethasone and Salvia miltiorrhiza can
      reduce the inflammatory reaction, regulate apoptosis, and thus protect multiple
      organs of rats with SAP.

PMID- 23125088
TI  - Immunological effects of a 10-MUg dose of domestic hepatitis B vaccine in adults.
AB  - OBJECTIVE: To evaluate the immunological effects of three types of domestic 10
      ug/dose hepatitis B vaccines in adults compared with a foreign vaccine, and to
      provide scientific evidence in support of adult hepatitis B vaccination. METHODS:
      Adults from five counties (Deqing, Changxing, Nanxun, Wuxing, Anji) in Huzhou
      City, Shaoxing County and Tongxiang County, Zhejiang Province, China were
      selected. Blood samples were taken to assess serum HBsAg, anti-HBs, and anti-HBc
      using a chemiluminescence immunoassay. Adults, aged 16 to 49 years and who were
      anti-HBs negative at baseline, received hepatitis B immunizations at 0, 1, and 6
      months. Anti-HBs levels were assessed one month after the third and final
      vaccination. RESULTS: A total of 1872 adults were immunized and the average
      positive rate was 89.5%. Four types of hepatitis B vaccine were used, including
      three from Chinese companies (Shenzhen Kangtai, Dalian High-Tech, and North China
      Pharmaceutical) and one from a UK company (GlaxoSmithKline). Their seroconversion
      rates were 81.67%, 95.05%, 89.64%, and 86.81%, respectively. There was a
      significant difference between the anti-HBs positive conversion rates of the four
      types (P<0.005) but the seroconversion rates among the different vaccines were
      not significantly different (chi(2)=2.123, P=0.145). The average anti-HBs
      geometric mean titers (GMTs) of non-immune adults immunized with each of the four
      vaccines were 177.28, 473.23, 246.13, and 332.20 mIU/ml, respectively. There were
      no statistically significant differences in the GMTs between the three types of
      domestic vaccine and the foreign vaccine (t=-1.575, P=0.116). CONCLUSIONS:
      Domestic recombinant hepatitis B vaccines can achieve immunization effects
      comparable to those of a foreign vaccine.

PMID- 23125089
TI  - Study on the PEG-based microwave-assisted extraction of flavonoid compounds from
      persimmon leaves.
AB  - A method for PEG-based microwave-assisted extraction (MAE) of flavonoid compounds
      from persimmon leaves has been successfully developed. The extraction efficiency
      of total flavonoid content was evaluated by the chromatographic peak areas of
      quercetin and kaempferol, which are two bioactive components typically found in
      persimmon leaves. The best combination of extraction parameters was obtained with
      response surface methodology. A microwave power of 525 W, liquid to solid ratio
      of 17:1 mL/g, and PEG aqueous solution concentration of 60% w/w were identified
      as the optimum parameters. Extraction dynamics analysis indicated that the
      quercetin, kaempferol, and total flavonoid contents were rising with increasing
      extraction time up to 20-25 min, from which point onwards they all decreased.
      Under the optimum conditions, quercetin, kaempferol, and total flavonoid contents
      obtained from the sample were 1.20 +/- 0.05, 0.64 +/- 0.11, and 16.90 +/- 0.06
      mg/g, respectively. Compared with ethanol-based MAE, and ethanol-based and PEG
      based ultrasonic-assisted extractions, PEG-based MAE had higher efficiency for
      the extraction of flavonoid compounds from persimmon leaves. Overall, PEG-based
      MAE represents an efficient choice for the extraction of bioactive substances
      from traditional Chinese medicines.

PMID- 23125091
TI  - Metal-free hydrogenation of electron-poor allenes and alkenes.

PMID- 23125090
TI  - Dimethylarginine-dimethylaminohydrolase-2 (DDAH-2) does not metabolize
      methylarginines.
AB  - Free endogenous methylarginines, N(omega)-monomethyl-L-arginine (L-NMMA) and
      N(omega),N(omega')-dimethyl-L-arginine (ADMA), inhibit NO synthases (NOSs) and
      are metabolized by dimethylargininedimethylaminohydrolase (DDAH). A postulated
      metabolism has been shown several times for DDAH-1, but the involvement of DDAH-2
      in the degradation of ADMA and L-NMMA is still a matter of debate. Determination
      of the isoform-specific DDAH protein expression profiles in various porcine
      tissue types shows a correlation of DDAH activity only with DDAH-1 levels. DDAH
      activity (measured as L-citrulline formation from the conversion of
      methylarginines and alternative DDAH substrates) was detected in DDAH-1-rich
      porcine tissue types, that is, kidney, liver, and brain, but not in DDAH-2-rich
      porcine fractions, that is, spleen and thyroid. Furthermore, several ex vivo
      studies showed DDAH activity to be important for L-citrulline formation in
      porcine tissue and indicated the absence of an endogenous DDAH inhibitor in
      porcine tissue. This study provides new insights into tissue distributions as
      well as substrate selectivity for both DDAH isoforms. Although DDAH-1 is known to
      metabolize the endogenous NOS inhibitors L-NMMA and ADMA, a physiological
      function for DDAH-2 has yet to be determined. Hence, determining DDAH activity by
      methylarginine conversion is not suitable for analyzing isoform selectivity of
      DDAH-1 inhibitors as postulated.

PMID- 23125092
TI  - Blood oxygen level-dependent liver MRI: can it predict microvascular invasion in
      HCC?
AB  - PURPOSE: To assess Blood Oxygen Level-Dependent (BOLD) Magnetic Resonance Imaging
      (MRI) for noninvasive preoperative prediction of Microvascular Invasion (MVI) in
      Hepatocellular Carcinoma (HCC). MATERIALS AND METHODS: In this prospective,
      institutional review board approved study, 26 patients (21 men and 5 women age
      range, 34-77 years with mean age of 61 years) with HCC were evaluated
      preoperatively with liver MRI including baseline and post oxygen (O2) breathing
      BOLD MRI. Post processing of MRI data was performed to obtain R2* values (1/s)
      and correlated with histopathological assessment of MVI. Statistical analysis was
      performed to assess correlation of baseline R2*, post O2 R2* and R2* ratios to
      presence of MVI in HCC by binary logistic regression analysis. RESULTS: MVI was
      present in 15/26 (58%) of HCC on histopathology. The mean R2* values +/- SD at
      baseline and post O2 with and without MVI were 35 +/- 12, 36 +/- 12, 38 +/- 10,
      42 +/- 17. The R2* values between the groups with and without MVI were not
      significantly different statistically. CONCLUSION: BOLD MRI is unable to
      accurately predict MVI in HCC. The noninvasive preoperative MRI detection of MVI
      in HCC remains elusive.

PMID- 23125093
TI  - Association between thyroxine levels at birth and choanal atresia or stenosis
      among infants in Texas, 2004-2007.
AB  - BACKGROUND: The causes of choanal atresia or stenosis (CA) are largely unknown.
      Infant thyroxine (T(4) ) levels collected during newborn screening may be proxy
      measures for a risk factor present during the critical period of development.
      Therefore, we conducted a case-control study to examine the association between
      newborn T(4) levels and CA. METHODS: Data for cases with CA and controls were
      obtained from the Texas Birth Defects Registry for the period of 2004 to 2007.
      Information on infant T(4) levels at birth was obtained from the Texas Newborn
      Screening Program. Controls (n = 3570) were drawn from unaffected births in Texas
      for the same period and frequency matched to cases (n = 69) on year of birth,
      then linked to the newborn screening database. Logistic regression was used to
      evaluate the association between continuous and categorical infant T(4) levels
      and nonsyndromic CA. RESULTS: After adjustment for gestational age and year of
      birth, infant T(4) levels were inversely associated with CA (adjusted odds ratio
      [AOR], 0.85; 95% confidence interval [CI], 0.80-0.90). We observed a linear trend
      (p < 0.001) across quartiles of T(4) ; compared to infants with low levels, AORs
      for CA were 0.50 (95% CI, 0.28-0.91), 0.39 (95% CI, 0.20-0.75), and 0.15 (95% CI,
      0.06-0.40) for infants with medium-to-low, medium, and high levels, respectively.
      CONCLUSIONS: Our findings suggest a role of low thyroid hormone levels in the
      development of CA, or that low newborn T(4) levels are potential proxy measures
      of a risk factor present during the critical period. Birth Defects Research (Part
      A), 2012.

PMID- 23125094
TI  - Mutations in NLRP7 and KHDC3L confer a complete hydatidiform mole phenotype on
      digynic triploid conceptions.
AB  - Digynic triploidy is classically associated with a severely growth restricted
      fetus and a small nonmolar placenta. However, in genotyping hydatidiform moles as
      part of clinical practice, we identified two digynic triploid conceptions
      presenting with histopathological features of classical complete hydatidiform
      mole (CHM). Both cases occurred in women with a history of previous molar
      pregnancies and no normal pregnancies. Pathological review and genotyping of
      other molar pregnancies in these cases showed them to be typical CHM with
      negative p57(KIP2)  immunostaining of the cytotrophoblast cells and villous
      stroma and to be diploid but biparental, confirming a diagnosis of familial
      recurrent hydatidiform mole (FRHM). Mutation screening of NLRP7 had identified a
      homozygous duplication, leading to a truncated protein, in case 1 whereas
      mutation screening of KHDC3L (C6orf221) in case 2 showed both the proband and her
      sister to be compound heterozygotes for mutations in KHDC3L. The observation of a
      single digynic, triploid conception presenting as a CHM in women with FRHM, where
      other pregnancies are diploid and biparental, supports the hypothesis that the
      role of both NLRP7 and KHDC3L in pregnancy is in setting and/or maintaining the
      maternal imprint. Clinically, a diagnosis of FRHM should be considered in women
      with genetically unusual conceptions that are phenotypically CHM.

PMID- 23125095
TI  - Evaluation of matrix solid-phase dispersion extraction for the determination of
      polycyclic aromatic hydrocarbons in household dust with the aid of experimental
      design and response surface methodology.
AB  - A simple, fast, and inexpensive procedure for sample preparation based on matrix
      solid-phase dispersion was developed for the determination of Environmental
      Protection Agency 16 priority polycyclic aromatic hydrocarbons in indoor dust
      samples. Parameters that affect the extraction efficiency such as type of
      dispersant, elution solvent, and solvent volume were evaluated and optimized with
      the aid of experimental design and response surface methodology. Analysis was
      performed by HPLC coupled with UV-Vis diode array detector (UV-DAD). For
      verification, a GC coupled with a mass spectrometer in SIM mode was also applied.
      Recoveries obtained were from 53 to 120% for all target analytes with detection
      limits ranging from 0.2 to 10 ng/g and 0.2 to 2 ng/g for LC-UV-DAD and GC-MS,
      respectively. The optimized method was used for the analysis of 11 household dust
      samples collected from private houses.

PMID- 23125096
TI  - Estimating the unit costs of public hospitals and primary healthcare centers.
AB  - BACKGROUND: Many factors have affected the rise of health expenditures, such as
      high-cost medical technologies, changes in disease patterns and increasing demand
      for health services. All countries allocate a significant portion of resources to
      the health sector. In 2008, the gross domestic product of Palestine was estimated
      to be at $6.108bn (current price) or about $1697 per capita. Health expenditures
      are estimated at 15.6% of the gross domestic product, almost as much as those of
      Germany, Japan and other developed countries. The numbers of hospitals, hospital
      beds and primary healthcare centers in the country have all increased. The
      Ministry of Health (MOH) currently operates 27 of 76 hospitals, with a total of
      3074 beds, which represent 61% of total beds of all hospitals in the Palestinian
      Authorities area. Also, the MOH is operating 453 of 706 Primary Health Care
      facilities. By 2007, about 40 000 people were employed in different sectors of
      the health system, with 33% employed by the MOH. AIM: This purpose of this study
      was to develop a financing strategy to help cover some or all of the costs
      involved in operating such institutions and to estimate the unit cost of primary
      and secondary programs and departments. METHODS: A retrospective study was
      carried out on data from government hospitals and primary healthcare centers to
      identify and analyze the costs and output (patient-related services) and to
      estimate the unit cost of health services provided by hospitals and PHCs during
      the year 2008. All operating costs are assigned and allocated to the departments
      at MOH hospitals and primary health care centers (PPHCs) and are identified as
      overhead departments, intermediate-service and final-service departments.
      Intermediate-service departments provide procedures and services to patients in
      the final-service departments. The costs of the overhead departments are
      distributed to the intermediate-service and final-service departments through a
      step-down method, according to allocation criteria devised to resemble as closely
      as possible the actual use of resources by each of the departments. The data were
      analyzed using spss. Data cleaning was carried out by cross-validating the
      results through conducting cross-tabulations between the hospital/center and
      section/program to identify errors from the data collection or entry process.
      Depreciation of assets and the consumption of capital costs are ignored in this
      study, as it is difficult to evaluate the MOH facilities owing to a lack of
      recording of depreciation of assets or other costs of servicing capital assets.
      RESULTS: Inpatient costs contributed about 75% of all costs, whereas outpatient
      services contributed the remaining 25% of total costs. The average cost per visit
      was $13.00 for outpatient departments, whereas the average cost per patient day
      for inpatient departments was $90.00. As for the unit cost for each department,
      intensive care unit and intermediate care unit services were the highest among
      all categories of daily hospital services ($208.00). This is in contrast to
      surgical operations ($124.00), specialized surgeries ($106.00), delivery
      department ($99.00), orthopedics ($98.50) and general surgery ($85.00). The
      lowest unit cost was found in the neonatology department ($72.00). In PHCs, the
      unit cost per visit was highest for psychiatry programs ($26.00), followed by
      other programs ($21.50), chronic diseases ($21.00), maternal and child health
      ($11.50), preventive programs ($9.00) and general medicine ($6.50). The exchange
      rate listed by The Wall Street Journal as of Wednesday August 25, 2010 is 1 US
      dollar = 3.82 new Israeli shekel (NIS). CONCLUSION: The findings have
      implications for policy and decision making in the health sector in Palestine
      concerning the cost of services provided by hospitals and PHCs. The availability
      of a standardized data set for cost assessment would greatly enhance and improve
      the quality of financial information as well as efficiency in the use of scarce
      resources.

PMID- 23125097
TI  - Diffuse reflectance spectroscopy in Barrett's esophagus: developing a large field
      of-view screening method discriminating dysplasia from metaplasia.
AB  - We evaluated diffuse reflectance spectroscopy implemented as a small field-of
      view technique for discrimination of dysplasia from metaplasia in Barrett's
      esophagus as an adjuvant to autofluorescence endoscopy. Using linear discriminant
      analysis on 2579 spectra measured in 54 patients identified an optimum a 4
      wavelength classifier (at 485, 513, 598 and 629 nm). Sensitivity and specificity
      for a test data set were 0.67 and 0.85, respectively. Spectroscopic results show
      that this technique could be implemented in wide-field imaging mode to improve
      the accuracy of existing endoscopy techniques for finding early pre-malignant
      lesions in Barrett's esophagus. Results show that the discrimination occurs
      likely due to redistribution of blood content in the tissue sensed by the optical
      probing with the wavelength-dependent sampling depth.

PMID- 23125098
TI  - Glucocorticoid mediates water avoidance stress-sensitized colon-bladder cross
      talk via RSK2/PSD-95/NR2B in rats.
AB  - Unexpected environmental and social stimuli could trigger stress. Although coping
      with stress is essential for survival, long-term stress impacts visceral
      functions, and therefore, it plays a role in the development and exacerbation of
      symptoms of gastrointestinal/urogenital disorders. The aim of this study is to
      characterize the role of corticosterone in stress-sensitized colon-bladder cross
      talk, a phenomenon presumed to underlie the comorbidity of functional bowel and
      bladder disorders. Cystometry and protein/mRNA expression in the lumbosacral
      dorsal horn (L6-S1) in response to intracolonic mustard oil (MO) instillation
      were analyzed in female Wistar-Kyoto rats subjected to water avoidance stress
      (WAS; 1 h/day for 10 days) or sham stress (WAsham). Whereas it had no effect on
      baseline-voiding function, chronic stress upregulated plasma corticosterone
      concentration and dorsal horn spinal p90 ribosomal S6 kinase 2 (RSK2)
      protein/mRNA levels, and RSK2 immunoreactivity colocalized with NeuN-positive
      neurons. Intracolonic MO dose-dependently decreased intrercontraction intervals
      and threshold pressure, provoked spinal RSK2 and NR2B phosphorylation, and
      enhanced PSD-95-RSK2 and PSD-95-NR2B coupling. Intrathecal kaempferol (a RSK2
      activation antagonist; 30 min before MO instillation), bilateral adrenalectomy (7
      days prior the stress paradigm), and subcutaneous RU-38486 (a glucocorticoid
      receptor antagonist; 30 min daily before stress sessions), but not RU-28318 (a
      mineralocorticoid receptor antagonist), attenuated MO-induced bladder
      hyperactivity, protein phosphorylation, and protein-protein interactions in the
      WAS group. Our results suggest that stress-associated glucocorticoid release
      mediates WAS-dependent sensitization of colon-bladder cross-talk via the spinal
      RSK2/PSD-95/NR2B cascade and offer a possibility for developing pharmacological
      strategies for the treatment of stress-related pelvic pain.

PMID- 23125099
TI  - Xylosyl- and glucuronyltransferase functions of LARGE in alpha-dystroglycan
      modification are conserved in LARGE2.
AB  - LARGE-dependent modification enables alpha-dystroglycan (alpha-DG) to bind to its
      extracellular matrix ligands. Mutations in the LARGE gene and several others
      involved in O-mannosyl glycan synthesis have been identified in congenital and
      limb-girdle muscular dystrophies that are characterized by perturbed
      glycosylation and reduced ligand-binding affinity of alpha-DG. LARGE is a
      bifunctional glycosyltransferase that alternately transfers xylose and glucuronic
      acid, thereby generating the heteropolysaccharides on alpha-DG that confer its
      ligand binding. Although the LARGE paralog LARGE2 (also referred to as GYLTL1B)
      has likewise been shown to enhance the functional modification of alpha-DG in
      cultured cells, its enzymatic activities have not been identified. Here, we
      report that LARGE2 is also a bifunctional glycosyltransferase and compare its
      properties with those of LARGE. By means of a high-performance liquid
      chromatography-based enzymatic assay, we demonstrate that like LARGE, LARGE2 has
      xylosyltransferase (Xyl-T) and glucuronyltransferase (GlcA-T) activities, as well
      as polymerizing activity. Notably, however, the pH optima of the Xyl-T and GlcA-T
      of LARGE2 are distinct from one another and also from those of LARGE. Our results
      suggest that LARGE and LARGE2 catalyze the same glycosylation reactions for the
      functional modification of alpha-DG, but that they have different biochemical
      properties.

PMID- 23125100
TI  - Assessment of the efficacy of MRI for detection of changes in bone morphology in
      a mouse model of bone injury.
AB  - PURPOSE: To determine whether magnetic resonance imaging (MRI) could be used to
      track changes in skeletal morphology during bone healing using high-resolution
      micro-computed tomography (MUCT) as a standard. We used a mouse model of bone
      injury to compare MUCT with MRI. MATERIALS AND METHODS: Surgery was performed to
      induce a burr hole fracture in the mouse tibia. A selection of biomaterials was
      immediately implanted into the fractures. First we optimized the imaging
      sequences by testing different MRI pulse sequences. Then changes in bone
      morphology over the course of fracture repair were assessed using in vivo MRI and
      MUCT. Histology was performed to validate the imaging outcomes. RESULTS: The
      rapid acquisition with relaxation enhancement (RARE) sequence provided sufficient
      contrast between bone and the surrounding tissues to clearly reveal the fracture.
      It allowed detection of the fracture clearly 1 and 14 days postsurgery and
      revealed soft tissue changes that were not clear on MUCT. In MRI and MUCT the
      fracture was seen at day 1 and partial healing was detected at day 14.
      CONCLUSION: The RARE sequence was the most suitable for MRI bone imaging. It
      enabled the detection of hard and even soft tissue changes. These findings
      suggest that MRI could be an effective imaging modality for assessing changes in
      bone morphology and pathobiology.

PMID- 23125101
TI  - Palladium-catalyzed coupling of ortho-alkynylanilines with terminal alkynes under
      aerobic conditions: efficient synthesis of 2,3-disubstituted 3-alkynylindoles.

PMID- 23125103
TI  - Online transient micellar phase concentration of anions using CTAB in CE.
AB  - A transient micellar phase extractor using CTAB was described for the online
      sample concentration of various anionic analytes (drugs and herbicides) in CE.
      Stacking and separation was performed at neutral pH in coelectroosmotic flow in a
      hexadimethrine bromide coated fused-silica capillary. A micellar plug (e.g. 10 mM
      CTAB) was injected prior to hydrodynamic injection of the analytes prepared in
      aqueous organic solvent (e.g. with 30% ACN). In the presence of an electric
      field, the micelles interacted with the anions inside the capillary. This was
      followed by selective analyte focusing via the mechanism of micelle to solvent
      stacking. The micelles acted as transient extractor because the stacking ends
      when the injected micelles completely migrated through the boundary between the
      sample and micellar plug. Fundamental studies were performed (effect of
      surfactant concentration, etc.) and the technique yielded 13- to 30-fold
      improvements in peak height. A stacking CE method in conjunction with liquid
      liquid extraction was also tested for the detection of the herbicides fenoprop
      and mecoprop in fortified drinking water at analyte concentration levels relevant
      to Australian Drinking Water Guidelines.

PMID- 23125102
TI  - Moderately high intake of folic acid has a negative impact on mouse embryonic
      development.
AB  - BACKGROUND: The incidence of neural tube defects has diminished considerably
      since the implementation of food fortification with folic acid (FA). However, the
      impact of excess FA intake, particularly during pregnancy, requires
      investigation. In a recent study, we reported that a diet supplemented with 20
      fold higher FA than the recommended intake for rodents had adverse effects on
      embryonic mouse development at embryonic days (E)10.5 and 14.5. In this report,
      we examined developmental outcomes in E14.5 embryos after administering a diet
      supplemented with 10-fold higher FA than recommended to pregnant mice with and
      without a mild deficiency of methylenetetrahydrofolate reductase (MTHFR).
      METHODS: Pregnant mice with or without a deficiency in MTHFR were fed a control
      diet (recommended FA intake of 2 mg/kg diet for rodents) or an FA-supplemented
      diet (FASD; 10-fold higher than the recommended intake [20 mg/kg diet]). At
      E14.5, mice were examined for embryonic loss and growth retardation, and hearts
      were assessed for defects and for ventricular wall thickness. RESULTS: Maternal
      FA supplementation was associated with embryonic loss, embryonic delays, a higher
      incidence of ventricular septal defects, and thinner left and right ventricular
      walls, compared to mothers fed control diet. CONCLUSIONS: Our work suggests that
      even moderately high levels of FA supplementation may adversely affect fetal
      mouse development. Additional studies are warranted to evaluate the impact of
      high folate intake in pregnant women. Birth Defects Research (Part A), 2013. (c)
      2012 Wiley Periodicals, Inc.

PMID- 23125106
TI  - A selenium-substituted low-bandgap polymer with versatile photovoltaic
      applications.

PMID- 23125107
TI  - Levodopa infusion does not decrease the onset of abnormal involuntary movements
      in parkinsonian rats.
AB  - The short duration of effect of levodopa is linked to pulsatile stimulation of
      striatal dopamine receptors and dyskinesia induction. However, the recent
      introduction of intraduodenal (i.d.) infusions and novel oral controlled release
      formulations of l-dopa may prevent dyskinesia induction and reduce the severity
      of established involuntary movements. We have compared the effects of twice-daily
      intraperitoneal (i.p.) administration and daily i.d. infusion of l-dopa on the
      induction and expression of abnormal involuntary movements in 6-hydroxydopamine
      (6-OHDA)-lesioned rats. Animals were treated with either twice-daily i.p.
      administration of l-dopa/carbidopa (7.85/12.5 mg/kg) or an 8-hour i.d. infusion
      of l-dopa/carbidopa (20/5 mg/mL; infusion rate: 0.04 mL/h) for 14 days, after
      which treatments were switched between groups and continued for a further 14
      days. Pulsatile i.p. administration of l-dopa induced moderate to severe abnormal
      involuntary movements, which gradually increased in severity over the 14 days,
      but i.d. infusion of l-dopa induced abnormal involuntary movements of a similar
      severity. Switching from continuous i.d. to pulsatile i.p. administration of l
      dopa continued to provoke severe abnormal involuntary movements expression.
      Switching from pulsatile i.p. to continuous i.d. l-dopa administration did not
      alter the peak abnormal involuntary movement severity but tended to reduce their
      duration. Treatment with less pulsatile l-dopa administration using i.d. infusion
      does not reduce the risk of the appearance of dyskinesia. By contrast, the
      duration of established dyskinesia can be reduced by more continuous l-dopa
      delivery in agreement with clinical experience.

PMID- 23125109
TI  - FTIR microspectroscopy of selected rare diverse sub-variants of carcinoma of the
      urinary bladder.
AB  - Urothelial carcinomas of the bladder are a heterogeneous group of tumours,
      although some histological sub-variants are rare and sparsely reported in the
      literature. Diagnosis of sub-variants from conventional urothelial carcinoma can
      be challenging, as they may mimic the morphology of other malignancies or benign
      tumours and therefore their distinction is important. For the first time, the
      spectral pathology of some of these sub-variants has been documented by infrared
      microspectroscopy and an attempt made to profile their biochemistry. It is
      important not only to identify and separate the cancer-associated epithelial
      tissue spectra from common tissue features such as stroma or blood, but also to
      detect the signatures of tumour sub-variants. As shown, their spectroscopic
      signals can change dramatically as a consequence of differentiation. Example
      cases are discussed and compared with histological evaluations.

PMID- 23125110
TI  - Building high-throughput molecular junctions using indented graphene point
      contacts.

PMID- 23125111
TI  - Performance evaluation of ion-exchange chromatography in capillary format.
AB  - The performance of a recently introduced capillary ion-exchange chromatography
      system was explored. Experiments were conducted in isocratic mode with a
      commercial capillary anion-exchange column (id = 0.4 mm, L = 15 cm) using a five
      anion standard mixture. The achieved results were compared to the performance of
      a standard bore ion-exchange system (id = 4 mm, L = 15 cm), which was considered
      as a reference. The first-generation capillary columns exhibited a minimal
      reduced plate-height value below two witnessing a good packing quality and system
      performance. However, compared to the standard bore system the capillary system
      displayed an increased apparent C-term which could be due to a difference in
      packing morphology and/or possible external band-broadening contributions. For
      fast separations, the standard bore system outperformed the capillary system,
      while for complex separations both systems performed nearly equally well. In
      addition, the retention characteristics of the capillary system were
      investigated. To illustrate the suitability of the capillary system, the analysis
      of real-world water samples originating from two local Belgian rivers was
      demonstrated.

PMID- 23125112
TI  - Shifts in the ESR spectra of alkali-metal atoms (Li, Na, K, Rb) on helium
      nanodroplets.
AB  - He-droplet-induced changes of the hyperfine structure constants of alkali-metal
      atoms are investigated by a combination of relativistically corrected ab initio
      methods with a simulation of the helium density distribution based on He density
      functional theory. Starting from an accurate description of the variation of the
      hyperfine structure constant in the M-He diatomic systems (M=Li, Na, K, Rb) as a
      function of the interatomic distance we simulate the shifts induced by droplets
      of up to 10,000 (4)He atoms. All theoretical predictions for the relative shifts
      in the isotropic hyperfine coupling constants of the alkali-metal atoms attached
      to helium droplets of different size are then tied to a single, experimentally
      derived parameter of Rb.

PMID- 23125113
TI  - Surface energy engineered, high-resolution micropatterning of solution-processed
      reduced graphene oxide thin films.

PMID- 23125108
TI  - A meta-analysis of cerebellar contributions to higher cognition from PET and fMRI
      studies.
AB  - A growing interest in cerebellar function and its involvement in higher cognition
      have prompted much research in recent years. Cerebellar presence in a wide range
      of cognitive functions examined within an increasing body of neuroimaging
      literature has been observed. We applied a meta-analytic approach, which employed
      the activation likelihood estimate method, to consolidate results of cerebellar
      involvement accumulated in different cognitive tasks of interest and
      systematically identified similarities among the studies. The current analysis
      included 88 neuroimaging studies demonstrating cerebellar activations in higher
      cognitive domains involving emotion, executive function, language, music, timing
      and working memory. While largely consistent with a prior meta-analysis by
      Stoodley and Schmahmann ([2009]: Neuroimage 44:489-501), our results extended
      their findings to include music and timing domains to provide further insights
      into cerebellar involvement and elucidate its role in higher cognition. In
      addition, we conducted inter- and intradomain comparisons for the cognitive
      domains of emotion, language, and working memory. We also considered task
      differences within the domain of verbal working memory by conducting a comparison
      of the Sternberg with the n-back task, as well as an analysis of the differential
      components within the Sternberg task. Results showed a consistent cerebellar
      presence in the timing domain, providing evidence for a role in time keeping.
      Unique clusters identified within the domain further refine the topographic
      organization of the cerebellum.

PMID- 23125114
TI  - Testing the feasibility of a National Spina Bifida Patient Registry.
AB  - BACKGROUND: The purpose of this study was to describe the development and early
      implementation of a national spina bifida (SB) patient registry, the goal of
      which is to monitor the health status, clinical care, and outcomes of people with
      SB by collecting and analyzing patient data from comprehensive SB clinics.
      METHODS: Using a web-based, SB-specific electronic medical record, 10 SB clinics
      collected health-related information for patients diagnosed with
      myelomeningocele, lipomyelomeningocele, fatty filum, or meningocele. This
      information was compiled and de-identified for transmission to the Centers for
      Disease Control and Prevention (CDC) for quality control and analysis. RESULTS: A
      total of 2070 patients were enrolled from 2009 through 2011: 84.9% were younger
      than 18 years of age; 1095 were women; 64.2% were non-Hispanic white; 6.5% were
      non-Hispanic black or African American; and 24.2% were Hispanic or Latino.
      Myelomeningocele was the most common diagnosis (81.5%). CONCLUSIONS: The creation
      of a National Spina Bifida Patient Registry partnership between the CDC and SB
      clinics has been feasible. Through planned longitudinal data collection and the
      inclusion of additional clinics, the data generated by the registry will become
      more robust and representative of the population of patients attending SB clinics
      in the United States and will allow for the investigation of patient outcomes.

PMID- 23125115
TI  - Coronary and systemic arterial physiology and immunohistochemical markers related
      to early coronary arterial lesions in beagle dogs given the potassium channel
      opener, ZD6169, or the endothelin receptor antagonist, ZD1611.
AB  - We evaluated immunohistochemistry (von Willebrand Factor [vWF] or fibrinogen) and
      systemic and coronary arterial physiological parameters in beagle dogs to
      investigate early arterial lesions induced by the potassium channel opener,
      ZD6169, or the endothelin receptor antagonist, ZD1611. Dogs given an oral dose of
      ZD6169 (experiment 1) were terminated 1 day later and showed arterial and
      myocardial lesions. Minimal arterial lesions exhibited few condensed medial
      smooth muscle cells only, with others showing segmental medial necrosis
      occasionally with medial/adventitial acute inflammation. Intercellular
      immunostaining was seen in ostensibly normal tissue, where no pathology was
      present in conventionally stained sections. vWF and fibrinogen are valuable tools
      for detecting disruption of arterial integrity. In experiment 2, 2 dogs were
      given a single high dose of ZD6169 or ZD1611 and BP/HR monitored by conventional
      measures or telemetry. Substantially reduced systolic/diastolic BP and increased
      HR occurred within 10 min of ZD6169 infusion: ZD1611 caused minor BP decrease and
      HR increase. In experiment 3, both drugs given to anaesthetized dogs induced
      markedly exaggerated systolic phasic forward and reverse flow in left descending
      and right coronary arteries. Diastolic coronary artery flows were unaffected with
      ZD1611 and increased slightly with ZD6169. In both coronary arteries, the ZD1611
      induced increase in flows paralleled decreased resistance. 

PMID- 23125116
TI  - Evaluation of expression profiles of hematopoietic stem cell, endothelial cell,
      and myeloid cell antigens in spontaneous and chemically induced hemangiosarcomas
      and hemangiomas in mice.
AB  - It is unclear whether the process of spontaneous and chemically induced
      hemangiosarcoma and hemangioma formation in mice involves the transformation of
      differentiated endothelial cells (ECs) or recruitment of multipotential bone
      marrow-derived hematopoietic stem cells or endothelial progenitor cells (EPCs),
      which show some degree of endothelial differentiation. In the present study,
      immunohistochemical staining for hematopoietic stem cell markers (CD45 and CD34),
      EC markers (vascular endothelial growth factor receptor 2 [VEGFR2], CD31, and
      factor VIII-related antigen), and a myeloid lineage marker (CD14) was employed to
      better define the origin of hemangiosarcomas and hemangiomas in mice. Staining
      was negative for CD45, factor VIII-related antigen, and CD14 and positive for
      CD34, VEGFR2, and CD31, indicating that mouse hemangiosarcomas and hemangiomas
      are composed of cells derived from EPCs expressing CD34, VEGFR2, and CD31 but not
      factor VIII-related antigen. The lack of CD45 expression suggests that mouse
      vascular tumors may arise from EPCs that are at a stage later than hematopoietic
      stem cells. Since factor VIII-related antigen expression is known to occur later
      than CD31 expression in EPCs, our observations may indicate that these tumor
      cells are arrested at a stage prior to complete differentiation.  In addition,
      myeloid lineage cells do not appear to contribute to hemangiosarcoma and
      hemangioma formation in mice. 

PMID- 23125118
TI  - Naringenin degradation by the endophytic diazotroph Herbaspirillum seropedicae
      SmR1.
AB  - Several bacteria are able to degrade flavonoids either to use them as carbon
      sources or as a detoxification mechanism. Degradation pathways have been proposed
      for several bacteria, but the genes responsible are not known. We identified in
      the genome of the endophyte Herbaspirillum seropedicae SmR1 an operon potentially
      associated with the degradation of aromatic compounds. We show that this operon
      is involved in naringenin degradation and that its expression is induced by
      naringenin and chrysin, two closely related flavonoids. Mutation of fdeA, the
      first gene of the operon, and fdeR, its transcriptional activator, abolished the
      ability of H. seropedicae to degrade naringenin.

PMID- 23125117
TI  - Toxicology and carcinogenesis study of senna in C3B6.129F1-Trp53 tm1Brd N12
      haploinsufficient mice.
AB  - Senna is a pod or leaf of Senna alexandrina P. Mill and is used as a stimulant
      laxative. In the large intestine, bacterial enzymes reduce sennosides to rhein-9
      anthrone, the active form for the laxative effect. To determine the potential
      toxic effects of senna, a 5-week dose range finding study in the C57BL/6N mouse
      and a 40-week toxicology and carcinogenesis study in the C3B6.129F1-Trp53
      (tm1Brd) N12 haploinsufficient (p53(+/-)) mouse were conducted. In the 5-week
      study, C57BL/6N mice were exposed to up to 10,000 ppm senna in feed. Increased
      incidences of epithelial hyperplasia of the cecum and colon were observed in
      males and females exposed to 5,000 or 10,000 ppm senna. These intestinal lesions
      were not considered to be of sufficient severity to cause mortality and, thus, in
      the p53(+/-) mouse 40-week study, the high dose of 10,000 ppm was selected.
      Significant increases in the incidences of epithelial hyperplasia of the colon
      and cecum were observed at 10,000 ppm in p53(+/-) males and females, and the
      incidence of hyperplasia of the colon was significantly increased at 3,000 ppm in
      females. In conclusion, the large intestine was the major target of senna-induced
      toxicity in both wild-type and the p53(+/-) mouse model. There was no neoplastic
      change when senna was administered to p53(+/-) mouse. 

PMID- 23125119
TI  - Genetics of germination-arrest factor (GAF) production by Pseudomonas fluorescens
      WH6: identification of a gene cluster essential for GAF biosynthesis.
AB  - The genetic basis of the biosynthesis of the germination-arrest factor (GAF)
      produced by Pseudomonas fluorescens WH6, and previously identified as 4
      formylaminooxyvinylglycine, has been investigated here. In addition to inhibiting
      the germination of a wide range of grassy weeds, GAF exhibits a selective
      antimicrobial activity against the bacterial plant pathogen Erwinia amylovora. We
      utilized the in vitro response of E. amylovora to GAF as a rapid screen for loss
      of-function GAF phenotypes generated by transposon mutagenesis. A Tn5 mutant
      library consisting of 6364 WH6 transformants was screened in this Erwinia assay,
      resulting in the identification of 18 non-redundant transposon insertion sites
      that led to loss of GAF production in WH6, as confirmed by TLC analysis. These
      insertions mapped to five different genes and four intergenic regions. Three of
      these genes, including two putative regulatory genes (gntR and iopB homologues),
      were clustered in a 13 kb chromosomal region containing 13 putative ORFs. A GAF
      mutation identified previously as affecting an aminotransferase also maps to this
      region. We suggest that three of the genes in this region (a
      carbamoyltransferase, an aminotransferase and a formyltransferase) encode the
      enzymes necessary to synthesize dihydroGAF, the putative immediate precursor of
      GAF in a proposed GAF biosynthetic pathway. RT-qPCR analyses demonstrated that
      mutations in the gntR and iopB regulatory genes, as well as in a prtR homologue
      identified earlier as controlling GAF formation, suppressed transcription of at
      least two of the putative GAF biosynthetic genes (encoding the aminotransferase
      and formyltransferase) located in this 13 kb region.

PMID- 23125120
TI  - Induction of the NFkappa-B signal transduction pathway in response to
      Corynebacterium diphtheriae infection.
AB  - Corynebacterium diphtheriae, the causative agent of diphtheria, has been
      thoroughly studied with respect to toxin production and pili formation, while
      knowledge on host responses to C. diphtheriae infection is limited. In this
      study, we studied adhesion to and invasion of epithelial cells by different C.
      diphtheriae isolates. When NFkappa-B reporter cell lines were used to monitor the
      effect of C. diphtheriae infection on human cells, strain-specific differences
      were observed. While adhesion to host cells had no effect, a correlation of
      invasion rate with NFkappa-B induction was found, which indicates that
      internalization of bacteria is crucial for NFkappa-B induction.
      Immunofluorescence microscopy experiments used to support the reporter assays
      showed that translocation of p65, as a hallmark of NFkappa-B induction, was only
      observed in association with cell invasion by C. diphtheriae. Our data indicate
      that the response of epithelial cells to C. diphtheriae infection is determined
      by internalization of bacteria and that invasion of these cells is an active
      process; tetracycline-treated C. diphtheriae was still able to attach to host
      cells, but lost its ability to invade the cytoplasm. Recognition of pathogen
      associated molecular patterns such as pili subunits by membrane-bound receptors
      facing the outside of the cell is not sufficient for NFkappa-B induction.

PMID- 23125122
TI  - Perceptions of issues relating to exercise and joint health in rheumatoid
      arthritis: a UK-based questionnaire study.
AB  - OBJECTIVES: This questionnaire study investigated the perceptions of rheumatoid
      arthritis (RA) patients across the UK in relation to exercise and joint health.
      The validity of the measure was also assessed. METHODS: Members of the National
      Rheumatoid Arthritis Society (NRAS) with self-reported RA completed the
      questionnaire online. Items related to five factors that emerged from previous
      qualitative research. Participants responded using a five-point Likert-style
      scale (strongly disagree to strongly agree). The International Physical Activity
      Questionnaire (IPAQ) assessed physical activity. The model was tested using
      confirmatory factor analysis (LISREL 8.8); statistical analyses were conducted
      using the Statistical Package for the Social Sciences (SPSS). RESULTS: A total of
      247 responses were collected over 47 days (88% females; age: 18-77 years; disease
      duration: <1-51 years). Acceptable factorial validity was revealed (Satorra
      Bentler chi(2)  = 774.47, df = 454, p < 0.001, root mean squared error of
      approximation (RMSEA) = 0.05, 90% confidence interval RMSEA = 0.05-0.06,
      comparative fit index = 0.94, standardized root mean square residual = 0.09),
      with the following factor endorsements: 'Health professionals show exercise
      knowledge' (19%); 'Knowing what exercise should be done' (43%); 'Having to
      exercise because it is helpful' (72%); 'Worry about causing harm to joints'
      (44%); and 'Not wanting to exercise as joints hurt' (52%). Patient concerns about
      joint pain, joint harm and how to exercise were significantly associated with
      lower physical activity (p < 0.05). CONCLUSIONS: These results confirm that
      patients perceive exercise as beneficial. However, concerns about how to
      exercise, joint pain, causing harm to joints and a perceived lack of exercise
      knowledge among health professionals remain. Addressing these concerns may have
      implications for increasing physical activity within the RA population.

PMID- 23125121
TI  - Ventromedial-frontopolar prefrontal cortex atrophy correlates with insight loss
      in frontotemporal dementia and Alzheimer's disease.
AB  - Loss in insight is a major feature of frontotemporal dementia (FTD) but has been
      investigated relatively little. More importantly, the neural basis of insight
      loss is still poorly understood. The current study investigated insight deficit
      profiles across a large cohort of neurodegenerative patients (n = 81), including
      FTD and Alzheimer's disease (AD) patients. We employed a novel insight
      questionnaire, which tapped into changes across different domains: social
      interaction, emotion, diagnosis/treatment, language, and motivation. FTD subtypes
      varied considerably for insight loss, with the behavioral variant worst and the
      progressive non-fluent variant least affected. All other subtypes and AD showed
      milder but consistent insight loss. Voxel-based morphometry analysis revealed
      that overall insight loss correlated with ventromedial and frontopolar prefrontal
      atrophy, with exception of social interaction and emotion insight loss, which
      additionally correlated with lateral temporal and amygdala atrophy, respectively.
      Our results show that patients with neurodegenerative conditions show variable
      loss of insight, with ventromedial and frontopolar cortex regions appearing to be
      particularly important for insight.

PMID- 23125124
TI  - Characterisation of a label-free biosensor based on long period grating.
AB  - Optical fibre gratings, especially long period gratings, have been recently
      proposed as optical devices for biochemical sensing. A biochemical interaction
      along the grating portion induces a refractive index change and hence a change in
      the fiber transmission spectrum. This provides an alternative methodology with
      respect to other label-free optical approaches, such as surface plasmon
      resonance, interferometric configurations and optical resonators. The fibre
      biofunctionalization has been carried out by means of a novel chemistry using
      Eudragit L100 copolymer as opposed to the commonly used silanization procedure.
      Antigen-antibody interaction has been analysed by means of an IgG/anti-IgG
      bioassay. The biosensor was fully characterised, monitoring the kinetics during
      the antibody immobilization and the antigen interaction and achieving the
      calibration curve of the assay. A comparison of the biosensor performance was
      made by using two different long period gratings with distinct periods.

PMID- 23125123
TI  - Solid-state NMR spectroscopy of functional amyloid from a fungal hydrophobin: a
      well-ordered beta-sheet core amidst structural heterogeneity.
AB  - GrEASy fibrils: Hydrophobins are fungal proteins that assemble into an
      amphipathic fibrillar monolayer with amyloid properties and a hydrophobic face as
      water-resistant as Teflon. Solid-state NMR studies on EAS hydrophobin fibrils
      reveal direct evidence of a partial molecular rearrangement on assembly and an
      ordered beta-sheet-rich core in the context of a whole protein in this functional
      amyloid.

PMID- 23125126
TI  - Where's the evidence for gluten sensitivity?

PMID- 23125127
TI  - Revalidation seems to add little to the current appraisal process.

PMID- 23125128
TI  - Recovery of coma patient sparks confusion over when to ask about organ donation.

PMID- 23125129
TI  - Medicine's dystopian future.

PMID- 23125130
TI  - Second hospital is evacuated as New York struggles to recover from hurricane.

PMID- 23125131
TI  - Frequency-specific alternations in the amplitude of low-frequency fluctuations in
      schizophrenia.
AB  - Schizophrenia has been associated with abnormal task-related brain activation in
      sensory and motor regions as well as social cognition network. Recently, two
      studies investigated temporal correlation between resting-state functional
      magnetic resonance imaging (R-fMRI) low-frequency oscillations (LFOs) in
      schizophrenia but reported mixed results. This may be due to the different
      frequency bands used in these studies. Here we utilized R-fMRI to measure the
      amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) in
      three different frequency bands (slow-5: 0.01-0.027 Hz; slow-4: 0.027-0.08 Hz;
      and typical band: 0.01-0.08 Hz) in 69 patients with schizophrenia and 62 healthy
      controls. We showed that there were significant differences in ALFF/fALFF between
      the two bands (slow-5 and slow-4) in regions including basal ganglia, midbrain,
      and ventromedial prefrontal cortex. Importantly, we also identified significant
      interaction between frequency bands and groups in inferior occipital gyrus,
      precuneus, and thalamus. The results suggest that the abnormalities of LFOs in
      schizophrenia is dependent on the frequency band and suggest that future studies
      should take the different frequency bands into account when measure intrinsic
      brain activity.

PMID- 23125132
TI  - A supramolecular system for the electrochemically controlled release of cells.

PMID- 23125133
TI  - Model-based analysis on the extractability of information from data in dynamic
      fed-batch experiments.
AB  - Dynamic changes of physiological bioprocess parameters, e.g. a change in the
      specific growth rate MU, are frequently observed during industrial manufacturing
      as well as bioprocess development. A quantitative description of these variations
      is of great interest, since it can bring elucidation to the physiological state
      of the culture. The goal of this contribution was to show limitations and issues
      for the calculation of rates with regard to temporal resolution for dynamic fed
      batch experiments. The impact of measurement errors, temporal resolution and the
      physiological activity on the signal to noise ratio (SNR) of the calculated rates
      was evaluated using an in-silico approach. To make use of that in practice, a
      generally applicable rule of thumb equation for the estimation of the SNR of
      specific rates was presented. The SNR calculated by this rule of thumb equation
      helps with definition of sampling intervals and making a decision whether an
      observed change is statistically significant or should be attributed to random
      error. Furthermore, a generic reconciliation approach to remove random as well as
      systematic error from data was presented. This reconciliation technique requires
      only little prior knowledge. The validity of the proposed tools was checked with
      real data from a fed-batch culture of E. coli with dynamic variations due to feed
      profile.

PMID- 23125134
TI  - Exposure of pregnant mice to chlorpyrifos-methyl alters embryonic H19 gene
      methylation patterns.
AB  - The aim of this study was to identify whether chlorpyrifos methyl (CPM) exposure
      during pregnancy leads to changes in the methylation patterns of H19 gene. CPM 4,
      20, 100 mg/kg bw/day was administered to 4 pregnant mice per group between 7 and
      12 days post coitum (d.p.c.). Pregnant mice were killed at 13 d.p.c. The genomic
      methylation in primordial germ cells (PGCs) and fetal organs (the liver,
      intestine, and placenta) was examined. Four polymorphism sites in the H19 alleles
      of maternal (C57BL/6J) and paternal (CAST/Ei) alleles were identified at
      nucleotide position 1407, 1485, 1566, and 1654. The methylation patterns of 17
      CpG sites were analyzed. The methylation level in male and female PGCs was not
      altered by CPM treatment in the maternal allele H19. The methylation level of the
      paternal H19 allele was altered in only male PGCs in response to the CPM
      treatment. The methylation level at a binding site for the transcriptional
      regulator CTCF2 was higher than that at the CTCF1 binding site in all CPM-treated
      groups. In the placenta, the aggregate methylation level of H19 was 56.89%in
      control group. But, those levels were ranged from 47.7% to 49.89% after treatment
      with increasing doses of CPM. H19 gene from the liver and intestine of 13 d.p.c.
      fetuses treated with CPM was hypomethylated as compared with controls, although
      H19 mRNA expression was unaltered. In the placenta, H19 expression was slightly
      increased in the CPM-treated group, although not significantly. IGF2 expression
      levels were not significantly changed in the placenta. In conclusion, CPM
      exposure during pregnancy alters the methylation status of the H19 gene in PGCs
      and embryonic tissues. We infer that these alterations are likely related to
      changes in DNA demethylase activity.

PMID- 23125135
TI  - Profiling pluripotent stem cells and organelles using synchrotron radiation
      infrared microspectroscopy.
AB  - FTIR micro-spectroscopy is a sensitive, non-destructive and label-free method
      offering diffraction-limited resolution with high signal-to-noise ratios when
      combined with a synchrotron radiation source. The vibrational signature of
      individual cells was used to validate an alternative strategy for reprogramming
      induced pluripotent stem cells generated from amniocytes. The iPSC lines PB09 and
      PB10, were reprogrammed from the same amniocyte cell line using respectively the
      Oct54, Sox2, Lin28, and Nanog and the Oct4 and Sox2 transcription factor
      cocktail. We show that cells reprogrammed by the two different sets of
      transfection factors have similar spectral signatures after reprogramming, except
      for a small subpopulation of cells in one of the cell lines. Mapping HeLa cells
      at subcellular resolution, we show that the Golgi apparatus, the cytoplasm and
      the nucleus have a specific spectral signature. The CH(3):CH(2) ratio is the
      highest in the nucleus and the lowest in the Golgi apparatus/endoplasmic
      reticulum, in agreement with the membrane composition of these organelles. This
      is confirmed by specific staining of the organelles with fluorescent dyes.
      Subcellular differentiation of cell compartments is also demonstrated in living
      cells.

PMID- 23125136
TI  - Calcium-phosphate microprecipitates mimic microparticles when examined with flow
      cytometry.
AB  - There are increased levels of circulating microparticles (MPs) in several disease
      states. Flow cytometry is a common method to examine MPs, but their small size
      necessitates the use of markers to distinguish specifically MPs from artifact.
      Annexin V, which binds phosphatidylserine, is a commonly used marker for MP
      detection. Annexin V requires millimolar calcium ion for optimum binding. Ca(++)
      can precipitate with phosphate in phosphate-buffered saline (PBS). Calcium
      phosphate microprecipitates were formed by titrating Ca(++) into PBS and examined
      using flow cytometry. Calcium-phosphate microprecipitates were compared with MPs
      derived from aged donor blood units. Microprecipitates were ~0.7-0.9 MUm in
      diameter compared with standard beads of known size. The microprecipitates
      disappeared with the addition of Ca(++) chelator. When we added fluorescently
      labeled antibodies to microprecipitates, the median fluorescent signal increased
      with increasing Ca(++) concentration regardless of specificity of the antibody.
      When repeated with a biological sample, there was an apparent increase in the
      fluorescent signal that returned to baseline after Ca(++) chelation. The flow
      cytometry signal of calcium-phosphate microprecipitates overlaps with the MP
      signal. Since Ca(++) is essential for annexin V binding, it is essential to avoid
      artifacts from calcium-phosphate microprecipitates when using any buffer or
      biological fluid containing phosphate. This also highlights the potential utility
      of flow cytometry for the analysis of crystals in biological fluids.

PMID- 23125137
TI  - Recombinant expression and purification of the antimicrobial peptide magainin-2.
AB  - Magainin-2 (MAG2) is a polycationic antimicrobial peptide isolated from the skin
      of the African clawed frog Xenopus laevis. It has a wide spectrum of
      antimicrobial activities against gram-positive and gram-negative bacteria, fungi,
      and induces osmotic lysis of protozoa. MAG2 also possesses antiviral and
      antitumoral properties. These activities make this peptide a promising candidate
      for therapeutic applications. Recombinant expression systems are necessary for
      the affordable production of large amounts of the biologically active peptide. In
      this work, MAG2 has been cloned to the N-terminal of a family III carbohydrate
      binding module fused to the linker sequence (LK-CBM3) from Clostridium
      thermocellum; a formic acid recognition site was introduced between the two
      modules for chemical cleavage of the peptide. The recombinant protein MAG2-LK
      CBM3 was expressed in Escherichia coli BL21 (DE3) and MAG2 was successfully
      cleaved and purified from the fusion partner LK-CBM3. Its functionality was
      confirmed by testing its activity against gram-negative bacteria.

PMID- 23125138
TI  - Comparative effect of technical and commercial formulations of methamidophos on
      sperm quality and DNA integrity in mice.
AB  - Methamidophos (MET), widely used in developing countries, is a highly neurotoxic
      organophosphate pesticide that has been associated with male reproductive
      alterations. Commercial formulations of pesticides used by agricultural workers
      and urban sprayers are responsible for thousands of intoxications in developing
      countries and may not have the same effects as active pure ingredients.
      Therefore, we compared effects of MET technical (METt) and commercial (METc)
      grades on sperm quality and DNA integrity. Male mice were injected
      (intraperitoneal, i.p.) with METt or METc (3.75, 5, and 7 mg/kg bw/day/4 days)
      and sacrificed 24 h post-treatment. Sperm cells collected from epididymis-vas
      deferens were evaluated for quality parameters, DNA damage by the comet assay,
      and lipoperoxidation by malondialdehyde (MDA) production. Erythrocyte
      acetylcholinesterase (AChE) activity was evaluated by acetylthiocholine
      inhibition as an index of overall toxicity. A dose-dependent AChE inhibition was
      observed with both formulations. Sperm quality was decreased after treatment with
      both MET compounds, but the commercial formulation showed stronger effects; a
      similar profile was observed with the DNA damage, being METc more genotoxic. None
      MET formulation increased MDA, suggesting no peroxidative damage involved. In
      summary, the commercial formulation of MET was more reprotoxic and genotoxic than
      the active pure ingredient, highlighting that commercial formulations must be
      considered for more appropriate risk assessment of pesticide exposures.

PMID- 23125140
TI  - Munich hospital closes liver transplantation list after audit uncovers errors.

PMID- 23125139
TI  - Molecular photoacoustic tomography of breast cancer using receptor targeted
      magnetic iron oxide nanoparticles as contrast agents.
AB  - In this report, we present a breast imaging technique combining high-resolution
      near-infrared (NIR) light induced photoacoustic tomography (PAT) with NIR dye
      labeled amino-terminal fragments of urokinase plasminogen activator receptor
      (uPAR) targeted magnetic iron oxide nanoparticles (NIR830-ATF-IONP) for breast
      cancer imaging using an orthotopic mouse mammary tumor model. We show that
      accumulation of the targeted nanoparticles in the tumor led to photoacoustic
      contrast enhancement due to the high absorption of iron oxide nanoparticles
      (IONP). NIR fluorescence images were used to validate specific delivery of NIR830
      ATF-IONP to mouse mammary tumors. We found that systemic delivery of the targeted
      IONP produced 4- and 10-fold enhancement in photoacoustic signals in the tumor,
      compared to the tumor of the mice that received non-targeted IONP or control
      mice. The use of targeted nanoparticles allowed imaging of tumors located as deep
      as 3.1 cm beneath the normal tissues. Our study indicates the potential of the
      combination of photoacoustic tomography and receptor-targeted NIR830-ATF-IONP as
      a clinical tool that can provide improved specificity and sensitivity for breast
      cancer detection.

PMID- 23125141
TI  - Direct exchange of a ketone methyl or aryl group to another aryl group through C
      C bond activation assisted by rhodium chelation.

PMID- 23125142
TI  - Determination of binding curves via protein micropatterning in vitro and in
      living cells.
AB  - Quantification of protein interactions in living cells is of key relevance for
      understanding cellular signaling. With current techniques, however, it is
      difficult to determine binding affinities and stoichiometries of protein
      complexes in the plasma membrane. We introduce here protein micropatterning as a
      convenient and versatile method for such investigations. Cells are grown on
      surfaces containing micropatterns of capture antibody to a bait protein, so that
      the bait gets rearranged in the live cell plasma membrane. Upon interaction with
      the bait, the fluorescent prey follows the micropatterns, which can be readout
      with fluorescence microscopy. In this study, we addressed the interaction between
      Lck and CD4, two central proteins in early T-cell signaling. Binding curves were
      recorded using the natural fluctuations in the Lck expression levels.
      Surprisingly, the binding was not saturable up to the highest Lck expression
      levels: on average, a single CD4 molecule recruited more than nine Lck molecules.
      We discuss the data in view of protein- and lipid-mediated interactions.

PMID- 23125143
TI  - An in vitro study of the photodynamic effect of rose bengal on Trichophyton
      rubrum.
AB  - Onychomycosis, a fungal infection of the finger or toenails, is predominantly
      caused by Trichophyton rubrum. Treatment is difficult due to high recurrence
      rates and problems with treatment compliance. For these reasons, alternative
      therapies are needed. Here we describe the photoactivation of Rose Bengal (RB)
      using a green laser (lambda = 532 nm) at fluences of 68, 133 and 228 J/cm(2) ,
      and assess its fungicidal activity on T. rubrum spore suspensions. A 140 uM RB
      solution was able to induce a fungicidal effect on T. rubrum when photosensitized
      with the fluence of 228 J/cm(2) . RB photosensitization using a green laser
      provides a potential novel treatment for T. rubrum infections.

PMID- 23125144
TI  - Apoptosis in normal and Coxiella burnetii-infected placentas from Alaskan
      northern fur seals (Callorhinus ursinus).
AB  - In 2010, Coxiella burnetii was identified in 75% of northern fur seal placentas
      from a single rookery in Alaska, but nothing was known about the significance of
      this organism in the population. Although many infectious organisms cause
      increased cell death, C. burnetii has been shown to suppress apoptosis of the
      host macrophages as an intracellular survival mechanism. To determine if
      infection induces a similar functional change in the placenta,
      immunohistochemistry for antibodies to cleaved caspase-3 (activated caspase-3)
      and the (TDT)-mediated dUTP-digoxigenin nick end labeling (TUNEL) technique were
      used to compare the amount of placental apoptosis in infected and noninfected
      placentas. There was a statistically significant difference in the frequency of
      apoptotic cells between infected and uninfected placentas, with more apoptosis
      identified in the uninfected placentas. This finding suggests that the survival
      mechanism of C. burnetii in host macrophages to reduce apoptosis may also be
      utilized in trophoblasts. The significance of decreased trophoblastic apoptosis
      for the northern fur seal fetus requires further investigation.

PMID- 23125145
TI  - Molecular profiling reveals prognostically significant subtypes of canine
      lymphoma.
AB  - We performed genomewide gene expression analysis of 35 samples representing 6
      common histologic subtypes of canine lymphoma and bioinformatics analyses to
      define their molecular characteristics. Three major groups were defined on the
      basis of gene expression profiles: (1) low-grade T-cell lymphoma, composed
      entirely by T-zone lymphoma; (2) high-grade T-cell lymphoma, consisting of
      lymphoblastic T-cell lymphoma and peripheral T-cell lymphoma not otherwise
      specified; and (3) B-cell lymphoma, consisting of marginal B-cell lymphoma,
      diffuse large B-cell lymphoma, and Burkitt lymphoma. Interspecies comparative
      analyses of gene expression profiles also showed that marginal B-cell lymphoma
      and diffuse large B-cell lymphoma in dogs and humans might represent a continuum
      of disease with similar drivers. The classification of these diverse tumors into
      3 subgroups was prognostically significant, as the groups were directly
      correlated with event-free survival. Finally, we developed a benchtop diagnostic
      test based on expression of 4 genes that can robustly classify canine lymphomas
      into one of these 3 subgroups, enabling a direct clinical application for our
      results.

PMID- 23125147
TI  - On-target and nanoparticle-facilitated selective enrichment of peptides and
      proteins for analysis by MALDI-MS.
AB  - Over the course of the last decade, a number of investigators have come to
      appreciate that the surface of a MALDI target, after suitable modification, can
      be used for selective enrichment of peptides and proteins. More recently, surface
      modified nanoparticles (NPs) that readily co-crystallize in MALDI matrix, are not
      ionized by laser desorption/ionization, and do not interfere with MS have
      attracted interest as alternatives to surface-modified targets for selective
      enrichment of peptides and proteins. Surface-modified targets and NPs facilitate
      parallel processing of samples, and when used in conjunction with MALDI mass
      spectrometers with kHz lasers enable development of high-throughput proteomics
      platforms. Targets and NPs for reversed phase and ion exchange retention,
      selective enrichment of glycopeptides, selective enrichment of phosphopeptides,
      and immunoaffinity MS are described in conjunction with details regarding their
      preparation and utility. Commercial availability of the reagents and substrates
      required to prepare surface-modified targets and NPs is also discussed.

PMID- 23125146
TI  - Epidemic of salmonellosis in passerine birds in Switzerland with spillover to
      domestic cats.
AB  - A die-off of passerine birds, mostly Eurasian siskins (Carduelis spinus),
      occurred in multiple areas of Switzerland between February and March 2010.
      Several of the dead birds were submitted for full necropsy. Bacteriological
      examination was carried out on multiple tissues of each bird. At gross
      examination, common findings were light-tan nodules, 1 to 4 mm in diameter,
      scattered through the esophagus/crop. Histologically, a necroulcerative
      transmural esophagitis/ingluvitis was observed. Bacterial cultures yielded
      Salmonella enterica subsp. enterica serovar Typhimurium. At the same time, 2 pet
      clinics reported an unusual increase of domestic cats presented with fever,
      anorexia, occasionally dolent abdomen, and history of presumed consumption of
      passerine birds. Analysis of rectal swabs revealed the presence of S. Typhimurium
      in all tested cats. PFGE (pulsed field electrophoresis) analysis was performed to
      characterize and compare the bacterial isolates, and it revealed an
      indistinguishable pattern between all the avian and all but 1 of the feline
      isolates. Cloacal swabs collected from clinically healthy migrating Eurasian
      siskins (during autumn 2010) did not yield S. Typhimurium. The histological and
      bacteriological findings were consistent with a systemic infection caused by S.
      Typhimurium. Isolation of the same serovar from the dead birds and ill cats,
      along with the overlapping results of the PFGE analysis for all the animal
      species, confirmed a spillover from birds to cats through predation. The sudden
      increase of the number of siskins over the Swiss territory and their persistency
      during the whole winter of 2009-2010 is considered the most likely predisposing
      factor for the onset of the epidemic.

PMID- 23125148
TI  - Immobilization of Oenococcus oeni in lentikats(r) to develop malolactic
      fermentation in wines.
AB  - Entrapment of Oenococcus oeni into a polymeric matrix based on polyvinyl alcohol
      (PVA) (Lentikats(r)) was successfully used to get a better development of
      malolactic fermentation (MLF) in wine. The incubation of immobilized cells in a
      nutrient medium before starting the MLF, did not improve the degradation of malic
      acid. In only one day, 100% of conversion of malic acid was achieved using a high
      concentration of immobilized cells (0.35 g gel/ml of wine with a cell-loading of
      0.25 mg cells/mg of gel). While a low concentration of 0.21 g gel/ml of wine
      (cell-loading of 0.25 mg cells/mg of gel) needed 3 days to get a reduction of
      40%. The entrapped cells could be reused through six cycles (runs of 3 days),
      retaining 75% of efficacy for the conversion of malic acid into lactic acid. The
      immobilized cells in PVA hydrogels gave better performance than free cells
      because of the increase of the alcohol toleration. Consequently, the inhibitory
      effect of ethanol for developing MLF could be reduced using immobilized cells
      into PVA hydrogels.

PMID- 23125149
TI  - Cascade activation of Si-H, C-H, and Si-C bonds at a rhodium beta-diiminate
      complex.

PMID- 23125150
TI  - Biomarker responses in caged carp (Cyprinuscarpio) and native collected fish
      (Leporinus obtusidens) in the Rio de la Plata Estuary, Argentina.
AB  - Punta Lara is located in the Rio de la Plata estuary near industrial areas
      contaminated mainly by organic pollutants. In this work, the responses and status
      of hepatic biomarkers were studied in juvenile carp (Cyprinus carpio) by means of
      a 21-day field exposure in cages and collection of juvenile native fish
      (Leporinus obtusidens) at Punta Lara. The analyzed hepatic biomarkers were:
      enzymatic activity of glutathione-S-transferase (GST), catalase (CAT) and
      superoxide dismutase (SOD), lipid peroxidation level using the thiobarbituric
      acid reaction (TBARS), and CYP1A protein expression, condition factor (CF) and
      liver somatic (LSI) index. Taking into account oxidative stress responses, SOD
      activity was increased in both species, while CAT was increased in C. carpio and
      decreased in L. obtusidens; TBARS levels indicated that oxidative damage was
      possibly exerted only in L. obtusidens. Biotransformation responses mediated by
      CYP1A were observed in both species, while GST activity was induced mainly in
      carps. Considering morphometric indices, CF and LSI were significantly increased
      in carps while CF decreased in native species. The anthropogenic pollution
      detected in this study in Punta Lara was associated with differences in
      biomarkers on both fish species, although a different pattern of response was
      observed.

PMID- 23125151
TI  - Silk fibroin-based scaffolds for bone regeneration.
AB  - Porous scaffolds were prepared using regenerated Bombyx mori silk fibroin
      dissolved in water or hexafluoroisopropanol (HFIP). The effects of these two
      preparations on the formation and growth of new bone on implantation into the
      rabbit femoral epicondyle was examined. The aqueous-based fibroin (A-F) scaffold
      exhibited significantly greater osteoconductivity as judged by bone volume, bone
      mineral content, and bone mineral density at the implant site than the HFIP-based
      fibroin (HFIP-F) scaffold. Micro-CT analyses showed that the morphology of the
      newly formed bone differed significantly in the two types of silk fibroin
      scaffold. After 4 weeks of implantation, new trabecular bone was seen inside the
      pores of the A-F scaffold implant while the HFIP-F scaffold only contained
      necrotic cells. No trabecular bone was seen within the pores of the latter
      scaffolds, although the pores of these did contain giant cells and granulation
      tissue.

PMID- 23125152
TI  - Affinity chromatographic purification of human immunoglobulin a from Chinese
      hamster ovary cell culture supernatant.
AB  - Hexamer peptide ligand HWRGWV, initially screened from a solid phase
      combinatorial peptide library for immunoglobulins G (IgG) purification, is shown
      to also have potential for immunoglobulin A (IgA) purification. The determined
      dissociation constants for hIgA on HWRGWV resins at three different peptide
      densities from 0.11 to 0.55 meq/g fall in the range of 10(-6) -10(-7) M, which
      are somewhat lower than those for hIgG. Although relatively low dynamic binding
      capacity (DBC) in the range of 9.2-16.8 mg IgA/mL resin at linear flow rates from
      173 to 35 cm/h were obtained for IgA compared to IgG, the DBC value of HWRGWV for
      IgA is much greater than current commercially available affinity ligands.
      Although relatively lower binding affinity to secretory IgA compared to monomeric
      IgA was observed, the peptide ligand resins exhibit great potential for large
      scale purification of both human IgA and secretory IgA. Recoveries of 96.0% and
      94.3%, and purities of 90.3% and 91.7% were achieved for human IgA and secretory
      IgA purification, respectively, from spiked Chinese hamster ovary cell culture
      supernatants without an extra afterwash step. Over 95% in purities were achieved
      for IgA and secretory IgA with an extra afterwash step; however, the recoveries
      would decrease at least 15% and 40% for IgA and secretory IgA, respectively.

PMID- 23125153
TI  - Quantitative analysis of dynamic behavior of osteoblasts during in vitro
      formation of micro-mass cell cultures.
AB  - Improvements in bone tissue engineering require an understanding of cellular and
      tissue level behavior of osteoblast-like cells. Experiments indicate that in the
      absence of an anchoring material, intercellular adhesion may be based on signals
      that promote cell activity resulting in the formation of a spheroid cell-matrix.
      The aim of the present study is to investigate the formation of scaffold-free
      three-dimensional micro-mass cell spheroids in vitro, and to characterize
      quantitatively the cell movement. A new correlation based automated tracking
      method is evaluated in order to optimize the processing parameters and to
      identify statistical parameters that characterize the cell behavior. Results
      suggest that the temporal development of the mean distance of the cells to the
      center of gravity may be described by an exponential function, thus providing a
      characteristic time constant as a quantitative measure of cell dynamics. ((c)
      2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim). 

PMID- 23125154
TI  - Membrane proteomics by high performance liquid chromatography-tandem mass
      spectrometry: Analytical approaches and challenges.
AB  - Membrane proteins (MPs) play diverse biologically important structural and
      functional roles including molecular transport, cell communication, and signal
      transduction. The dysfunctions of many are linked to deleterious human diseases
      and thus are of utmost importance in drug discovery. MPs comprise approximately
      20-30% of all open reading frames (ORFs), however they are typically under
      represented in many LC-MS proteomics experiments due to their low abundance and
      poor solubility. To address these analytical challenges, various MP enrichment,
      solubilization, digestion, and fractionation strategies have been employed to
      further improve the coverage of the membrane systems while maintaining
      compatibility with MS detection. This review discusses both established and
      emerging high-throughput gel-free analytical workflows in membrane proteomics,
      and the inherent advantages, disadvantages, and orthogonality of the various
      approaches. The issues of critical importance for successful LC-MS/MS detection
      such as detergent selection and minimizing ion suppression in detergent-based
      workflows are discussed in detail. Recent studies comparing the performance of
      different analytical strategies are highlighted in order to provide practical
      insight into the choice of the most appropriate method for membrane-centric
      applications ranging from cell surface biomarker discovery to MP interaction
      network mapping.

PMID- 23125155
TI  - Critical role of interleukin-17A in murine intestinal ischemia-reperfusion
      injury.
AB  - Intestinal ischemia-reperfusion (I/R) injury causes severe illness frequently
      complicated by remote multiorgan dysfunction and sepsis. Recent studies
      implicated interleukin-17A (IL-17A) in regulating inflammation, autoimmunity, and
      I/R injury. Here, we determined whether IL-17A is critical for generation of
      intestinal I/R injury and subsequent liver and kidney injury. Mice subjected to
      30 min of superior mesenteric artery ischemia not only developed severe small
      intestinal injury (necrosis, apoptosis, and neutrophil infiltration) but also
      developed significant renal and hepatic injury. We detected large increases in IL
      17A in the small intestine, liver, and plasma. IL-17A is critical for generating
      these injuries, since genetic deletion of IL-17A- or IL-17A-neutralizing antibody
      treatment markedly protected against intestinal I/R injury and subsequent liver
      and kidney dysfunction. Intestinal I/R caused greater increases in portal plasma
      and small intestine IL-17A, suggesting an intestinal source for IL-17A
      generation. We also observed that intestinal I/R caused rapid small intestinal
      Paneth cell degranulation and induced murine alpha-defensin cryptdin-1
      expression. Furthermore, genetic or pharmacological depletion of Paneth cells
      significantly attenuated the intestinal I/R injury as well as hepatic and renal
      dysfunction. Finally, Paneth cell depletion significantly decreased small
      intestinal, hepatic, and plasma IL-17A levels after intestinal I/R. Taken
      together, we propose that Paneth cell-derived IL-17A may play a critical role in
      intestinal I/R injury as well as extraintestinal organ dysfunction.

PMID- 23125156
TI  - The guggulsterone derivative GG-52 inhibits NF-kappaB signaling in gastric
      epithelial cells and ameliorates ethanol-induced gastric mucosal lesions in mice.
AB  - Gastric mucosal inflammation can develop after challenge with noxious stimuli
      such as alcohol. Specially, alcohol stimulates the release of inflammatory
      cytokines but does not increase gastric acid secretion, leading to gastric
      mucosal damage. The plant sterol guggulsterone and its novel derivative GG-52
      have been reported to inhibit nuclear factor-kappaB (NF-kappaB) signaling in
      intestinal epithelial cells and experimental colitis. In the present study, we
      investigated the anti-inflammatory effects of GG-52 on gastric epithelial cells
      and on ethanol-induced gastric mucosal inflammation in mice. GG-52 inhibited the
      expression of interleukin-8 (IL-8) in gastric epithelial AGS and MKN-45 cell
      lines stimulated with tumor necrosis factor (TNF)-alpha in a dose-dependent
      manner. Pretreatment with GG-52 suppressed TNF-alpha-induced activation of
      IkappaB kinase (IKK) and NF-kappaB signaling in MKN-45 cells. In contrast, the
      inactive analog GG-46 did not produce significant changes in IL-8 expression or
      NF-kappaB activation. In a model of ethanol-induced murine gastritis,
      administration of GG-52 significantly reduced the severity of gastritis, as
      assessed by macroscopic and histological evaluation of gastric mucosal damage. In
      addition, the ethanol-induced upregulation of chemokine KC, a mouse homolog of IL
      8, and phosphorylated p65 NF-kappaB signals were significantly inhibited in
      murine gastric mucosa pretreated with GG-52. These results indicate that GG-52
      suppresses NF-kappaB activation in gastric epithelial cells and ameliorates
      ethanol-induced gastric mucosal lesions in mice, suggesting that GG-52 may be a
      potential gastroprotective agent.

PMID- 23125157
TI  - Vitamin D deficiency: protective against enteric infection?

PMID- 23125158
TI  - Oxidative modification of the intestinal mucus layer is a critical but
      unrecognized component of trauma hemorrhagic shock-induced gut barrier failure.
AB  - Recent studies demonstrate that mechanisms underlying gut barrier failure include
      systemic processes and less studied luminal processes. We thus tested the
      hypothesis that mucus layer oxidation is a component of trauma/hemorrhagic shock
      induced gut injury and dysfunction. Male Sprague-Dawley rats underwent
      trauma/hemorrhagic shock. Controls underwent trauma only. Mucus from the terminal
      30 cm of the ileum was collected, processed, and analyzed for reactive nitrogen
      intermediates (RNI)-mediated damage, reactive oxygen species (ROS)-induced
      damage, and total antioxidant capacity. The distal ileum was stained to quantify
      the mucus layer; gut permeability was assessed physiologically. A time course
      study was conducted to determine the temporal sequence of mucus layer damage. The
      role of free radical-mediated damage to the gut barrier was investigated by the
      effect of the free radical scavenger dimethyl sulfoxide on trauma/hemorrhagic
      shock-induced changes on the mucus and on gut permeability. Trauma/hemorrhagic
      shock increased intestinal permeability, which was associated with evidence of
      loss of the unstirred mucus layer. These changes correlated with increased ROS-
      and RNI-mediated mucus damage and loss of mucus total antioxidant capacity. Based
      on the time course study, ROS-mediated mucus damage and loss of total antioxidant
      capacity were present immediately following shock, whereas RNI-mediated damage
      was delayed for 3 h. Dimethyl sulfoxide ameliorated gut barrier loss, ROS
      mediated changes to the mucus layer, and loss of total antioxidant capacity.
      There was no change in RNI-induced changes to the mucus layer. These results
      support the hypothesis that trauma/hemorrhagic shock leads to mucus damage and
      gut dysfunction through the generation of free radical species.

PMID- 23125160
TI  - Neurologists appeal to health secretary over withdrawal of drug for MS patients.

PMID- 23125159
TI  - The hepatic bile acid transporters Ntcp and Mrp2 are downregulated in
      experimental necrotizing enterocolitis.
AB  - Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency of
      premature infants and is characterized by an extensive hemorrhagic inflammatory
      necrosis of the distal ileum and proximal colon. We have previously shown that,
      during the development of experimental NEC, the liver plays an important role in
      regulating inflammation in the ileum, and accumulation of ileal bile acids (BA)
      along with dysregulation of ileal BA transporters contributes to ileal damage.
      Given these findings, we speculated that hepatic BA transporters would also be
      altered in experimental NEC. Using both rat and mouse models of NEC, levels of
      Cyp7a1, Cyp27a1, and the hepatic BA transporters Bsep, Ntcp, Oatp2, Oatp4, Mrp2,
      and Mrp3 were investigated. In addition, levels of hepatic BA transporters were
      also determined when the proinflammatory cytokines tumor necrosis factor (TNF)
      alpha and interleukin (IL)-18, which are both elevated in NEC, are neutralized
      during disease development. Ntcp and Mrp2 were decreased in NEC, but elevated
      ileal BA levels were not responsible for these reductions. However,
      neutralization of TNF-alpha normalized Ntcp, whereas removal of IL-18 normalized
      Mrp2 levels. These data show that the hepatic transporters Ntcp and Mrp2 are
      downregulated, whereas Cyp27a1 is increased in rodent models of NEC. Furthermore,
      increased levels of TNF-alpha and IL-18 in experimental NEC may play a role in
      the regulation of Ntcp and Mrp2, respectively. These data suggest the gut-liver
      axis should be considered when therapeutic modalities for NEC are developed.

PMID- 23125161
TI  - Hydrogen-bond-mediated supramolecular iminium ion catalysis.

PMID- 23125162
TI  - Effects of dietary polyphenols on neuroregulatory factors and pathways that
      mediate food intake and energy regulation in obesity.
AB  - Polyphenols are natural substances and are enriched in vegetables, fruits,
      grains, bark, tea, and wine. Some polyphenols have insulin-potentiating and anti
      inflammatory effects, both of which are important in obesity. Dietary
      supplementation with polyphenolic compounds is associated with reduced diet
      induced obesity and/or metabolic syndrome in animal and human studies. Insights
      into mechanisms that regulate food intake and satiety have led to an increased
      understanding of obesity but the pathogenesis underlying obesity is lacking. Food
      intake is subject to a complex regulation by the hypothalamus and other brain
      centers including the brain stem and the hippocampus. An intricate network of
      interacting feedback mechanisms that involve the aforementioned neural centers
      along with the stomach, gut, liver, thyroid, and adipose tissue in the periphery,
      influence the eventual outcome of food intake and satiety. Key peripheral
      signals, such as leptin, insulin, and ghrelin, have been linked to hypothalamic
      neuropeptide systems in energy regulation. This review will examine the neural
      centers important in food intake, the role of various neuropeptides, and the
      neurohormonal influence on food intake. The potential role of polyphenols in
      influencing the neuroregulatory factors, the neural signaling pathways and/or the
      peripheral feedback mechanisms that modulate food intake will also be examined.

PMID- 23125163
TI  - Carbon and clay nanoparticles induce minimal stress responses in gram negative
      bacteria and eukaryotic fish cells.
AB  - We investigated in vitro the potential mutagenic and toxic effects of two clay
      based nanoparticles, Cloisite(r) Na(+) (Cloisite) and halloysite; and multi
      walled carbon nanotubes (MWCNT), commonly used in the polymer composite industry.
      Using the Ames test, the three nanoparticles did not have a true mutagenic
      effect, although growth of Salmonella enterica var. Typhimurium (S.typhimurium)
      was diminished at higher nanoparticle concentrations. We investigated the impact
      of nanoparticles on Escherichia coli and S. typhimurium including oxyR and rpoS
      mutants, which are susceptible to oxidative stress. The oxyR mutants were
      inhibited in the presence of nanoparticles, when grown aerobically with light.
      Toxicity was not observed in the absence of light or during anaerobic growth. E.
      coli rpoS mutants exhibited some toxicity when cultured with Cloisite and MWCNT
      only when grown aerobically with light. There was no effect with other
      nanoparticles, or with S. typhimurium rpoS mutants. MWCNT exhibited a slight
      toxic effect against Epithelioma papulosum cyprini (EPC) cells only at the
      highest concentration tested. There was no discernable toxicity to EPC cells
      caused by the clay nanoparticles. We conclude that clay-based nanoparticles and
      MWCNT do not exert a mutagenic effect and do not have a general toxic effect
      across all bacterial species or between prokaryotic and eukaryotic cells. Modest
      toxicity was only observed in eukaryotic EPC cells against MWCNT at the highest
      concentration tested. Limited species-specific toxicity to clay based and MWCNT
      nanoparticles was seen in bacterial strains primarily due to culture conditions
      and mutations that exacerbate oxidative stress.

PMID- 23125165
TI  - Siloxides as supporting ligands in uranium(III)-mediated small-molecule
      activation.

PMID- 23125164
TI  - Proteomics for understanding miRNA biology.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs that play important roles in
      posttranscriptional regulation of gene expression. Mature miRNAs associate with
      the RNA interference silencing complex to repress mRNA translation and/or degrade
      mRNA transcripts. Mass spectrometry-based proteomics has enabled identification
      of several core components of the canonical miRNA processing pathway and their
      posttranslational modifications which are pivotal in miRNA regulatory mechanisms.
      The use of quantitative proteomic strategies has also emerged as a key technique
      for experimental identification of miRNA targets by allowing direct determination
      of proteins whose levels are altered because of translational suppression. This
      review focuses on the role of proteomics and labeling strategies to understand
      miRNA biology.

PMID- 23125167
TI  - High Court quashes suspension of GP who was alleged to have been involved in a
      "cash for crash" scam.

PMID- 23125166
TI  - Cryopreservation of pluripotent stem cell aggregates in defined protein-free
      formulation.
AB  - Cultivation of undifferentiated pluripotent stem cells (PSCs) as aggregates has
      emerged as an efficient culture configuration, enabling rapid and controlled
      large scale expansion. Aggregate-based PSC cryopreservation facilitates the
      integrated process of cell expansion and cryopreservation, but its feasibility
      has not been demonstrated. The goals of current study are to assess the
      suitability of cryopreserving intact mouse embryonic stem cell (mESC) aggregates
      and investigate the effects of aggregate size and the formulation of
      cryopreservation solution on mESC survival and recovery. The results demonstrated
      the size-dependent cell survival and recovery of intact aggregates. In
      particular, the generation of reactive oxygen species (ROS) and caspase
      activation were reduced for small aggregates (109 +/- 55 MUm) compared to medium
      (245 +/- 77 MUm) and large (365 +/- 141 MUm) ones, leading to the improved cell
      recovery. In addition, a defined protein-free formulation was tested and found to
      promote the aggregate survival, eliminating the cell exposure to animal serum.
      The cryopreserved aggregates also maintained the pluripotent markers and the
      differentiation capacity into three-germ layers after thawing. In summary, the
      cryopreservation of small PSC aggregates in a defined protein-free formulation
      was shown to be a suitable approach toward a fully integrated expansion and
      cryopreservation process at large scale.

PMID- 23125170
TI  - Number needed to treat in COPD: exacerbations versus pneumonias.
AB  - BACKGROUND: Several recent trials in chronic obstructive pulmonary disease (COPD)
      have assessed the effectiveness of the fluticasone-salmeterol combination inhaler
      in preventing COPD exacerbations, while finding an increased risk of pneumonia.
      The number needed to treat (NNT) is a simple measure to perform the comparative
      benefit-risk impact, but its calculation involving repeated outcome events such
      as COPD exacerbations has been incorrect. We describe the proper methods to
      calculate the NNT and, using data from published trials, apply them to evaluate
      the relative impact of fluticasone-salmeterol treatment on exacerbations and
      pneumonias in patients with COPD. METHODS: We review the fundamental definition
      of NNT and quantify it for situations with varying follow-up times. We review the
      'event-based' NNT, proposed and used for repeated event outcomes, show its
      inaccuracy, describe its proper use and provide an approximate formula for its
      application. RESULTS: We show that a 1-year trial of the fluticasone-salmeterol
      combination versus salmeterol used the incorrect event-based approach to
      calculate the NNT as two patients that need to be treated for 1 year to prevent
      one COPD exacerbation, when the proper calculation results in a NNT of 14. In
      contrast, 20 patients need to be treated to induce one pneumonia case. For the
      TORCH trial, the NNT is 44 patients treated for 3 years with fluticasone
      salmeterol versus salmeterol to prevent one exacerbation compared with 16
      patients to induce one pneumonia case. CONCLUSIONS: The NNT is a useful measure
      of the effect of drugs, but its proper calculation is essential to prevent
      misleading clinical practice guidelines.

PMID- 23125172
TI  - Downstream processing, characterization, and structure-function relationship of
      solvent-, detergent-, psychro-, thermo-, alkalistable metalloprotease from metal
      , solvent-tolerant psychrotrophic Pseudomonas putida SKG-1 isolate.
AB  - The purification and characterization of psychro-thermoalkalistable protease from
      psychrotrophic Pseudomonas putida isolate is being reported for the first time. A
      ~53 kDa protease was purified 21.4-folds with 57.2% recovery by ultrafiltration
      and hydrophobic interaction chromatography. Kinetic analyses revealed the K(m)
      and V(max) to be 1.169 mg mL(-1) and 0.833 mg mL(-1) min(-1) , respectively. The
      k(cat) value of 3.05 * 10(2) s(-1) indicated high affinity and catalytic
      efficiency toward casein. The protease was most active at pH 9.5 and 40 degrees
      C, with 100% stability in pH and temperature range of 6.0-11.0 and 10-40 degrees
      C, respectively. Presence of Zn(2+) increased the thermostability of protease (at
      70 degrees C) by 433%. Ethylene diamine tetra acetic acid (EDTA) and 1,10
      phenanthroline were inhibitory, whereas phenyl methyl sulfonyl fluoride (PMSF), p
      chloro mercuric benzoate (PCMB), and beta-mercaptoethanol were ineffective,
      revealing the enzyme to be a metalloprotease. Zinc, calcium, iron, nickel, and
      copper at 1 mM increased the enzyme activity (102-134%). Complete reversion of
      enzyme inhibition (caused by Ethylene diamine tetra acetic acid [EDTA]) by Zn(2+)
      affirmed this enzyme as zinc-dependent metalloprotease. At 0.1% concentration,
      Triton X-100 and Tween 80 slightly increased, while SDS and H(2) O(2) reduced the
      protease activity. In the presence of 0.1% commercial detergents, the enzyme was
      fairly stable (54-81%). In the presence of organic solvent, the protease was
      remarkably stable exhibiting 72-191% activities. In contrast, savinase exhibited
      good stability in the presence of hydrophilic solvents, while chymotrypsin showed
      elevated activities with benzene, toluene, and xylene only. Circular dichroism
      analysis revealed the protease as a beta-rich protein, having large fraction
      (~40%) of beta-sheets. Presence of different environmental conditions altered the
      beta-content, which accordingly affected the protease activity.

PMID- 23125173
TI  - Sex-related shape dimorphism in the human radiocarpal and midcarpal joints.
AB  - Previous research has revealed significant size differences between human male
      and female carpal bones but it is unknown if there are significant shape
      differences as well. This study investigated sex-related shape variation and
      allometric patterns in five carpal bones that make up the radiocarpal and
      midcarpal joints in modern humans. We found that many aspects of carpal shape
      (76% of all variables quantified) were similar between males and females, despite
      variation in size. However, 10 of the shape ratios were significantly different
      between males and females, with at least one significant shape difference
      observed in each carpal bone. Within-sex standard major axis regressions (SMA) of
      the numerator (i.e., the linear variables) on the denominator (i.e., the
      geometric mean) for each significantly different shape ratio indicated that most
      linear variables scaled with positive allometry in both males and females, and
      that for eight of the shape ratios, sex-related shape variation is associated
      with statistically similar sex-specific scaling relationships. Only the length of
      the scaphoid body and the height of the lunate triquetrum facet showed a
      significantly higher SMA slope in females compared with males. These findings
      indicate that the significant differences in the majority of the shape ratios are
      a function of subtle (i.e., not statistically significant) scaling differences
      between males and females. There are a number of potential developmental,
      functional, and evolutionary factors that may cause sex-related shape differences
      in the human carpus. The results highlight the potential for subtle differences
      in scaling to result in functionally significant differences in shape.

PMID- 23125171
TI  - Tissue proteomics in pancreatic cancer study: discovery, emerging technologies,
      and challenges.
AB  - Pancreatic cancer is a highly lethal disease that is difficult to diagnose and
      treat. The advances in proteomics technology, especially quantitative proteomics,
      have stimulated a great interest in applying this technology for pancreatic
      cancer study. A variety of tissue proteomics approaches have been applied to
      investigate pancreatic cancer and the associated diseases. These studies were
      carried out with various goals, aiming to better understand the molecular
      mechanisms underlying pancreatic tumorigenesis, to improve therapeutic treatment
      and to identify cancer associated protein signatures, signaling events as well as
      interactions between cancer cells and tumor microenvironment. Here, we provide an
      overview on the tissue proteomics studies of pancreatic cancer reported in the
      past few years in light of discovery and technology development.

PMID- 23125175
TI  - Tensilely strained germanium nanomembranes as infrared optical gain media.
AB  - The use of tensilely strained Ge nanomembranes as mid-infrared optical gain media
      is investigated. Biaxial tensile strain in Ge has the effect of lowering the
      direct energy bandgap relative to the fundamental indirect one, thereby
      increasing the internal quantum efficiency for light emission and allowing for
      the formation of population inversion, until at a strain of about 1.9% Ge is even
      converted into a direct-bandgap material. Gain calculations are presented showing
      that, already at strain levels of about 1.4% and above, Ge films can provide
      optical gain in the technologically important 2.1-2.5 MUm spectral region, with
      transparency carrier densities that can be readily achieved under realistic
      pumping conditions. Mechanically stressed Ge nanomembranes capable of
      accommodating the required strain levels are developed and used to demonstrate
      strong strain-enhanced photoluminescence. A detailed analysis of the high-strain
      emission spectra also demonstrates that the nanomembranes can be pumped above
      transparency, and confirms the prediction that biaxial-strain levels in excess of
      only 1.4% are required to obtain significant population inversion.

PMID- 23125174
TI  - Single-round, multiplexed antibody mimetic design through mRNA display.
AB  - In a single round: By combining the high-efficiency enrichment through the
      continuous-flow magnetic separation (CFMS) technique with the analytical power of
      next-generation sequencing, the generation of antibody mimetics with a single
      round of mRNA display is made possible. This approach eliminates iterative
      selection cycles and provides a path to fully automated ligand generation (see
      picture).

PMID- 23125176
TI  - Project to increase availability of malaria drug has worked, study finds.

PMID- 23125177
TI  - Avidity-mediated virus separation using a hyperthermophilic affinity ligand.
AB  - Immunoaffinity separation of large multivalent species such as viruses is limited
      by the stringent elution conditions necessary to overcome their strong and highly
      avid interaction with immobilized affinity ligands on the capture surface. Here
      we present an alternate strategy that harnesses the avidity effect to overcome
      this limitation. Red clover necrotic mosaic virus (RCNMV), a plant virus relevant
      to drug delivery applications, was chosen as a model target for this study. An
      RCNMV binding protein (RBP) with modest binding affinity (K(D) ~100 nM) was
      generated through mutagenesis of the Sso7d protein from Sulfolobus solfataricus
      and used as the affinity ligand. In our separation scheme, RCNMV is captured by a
      highly avid interaction with RBP immobilized on a nickel surface through a
      hexahistidine (6xHis) tag. Subsequently, disruption of the multivalent
      interaction and release of RCNMV is achieved by elution of RBP from the nickel
      surface. Finally, RCNMV is separated from RBP by exploiting the large difference
      in their molecular weights (~8 MDa vs. ~10 kDa). Our strategy not only eliminates
      the need for harsh elution conditions, but also bypasses chemical conjugation of
      the affinity ligand to the capture surface. Stable non-antibody affinity ligands
      to a wide spectrum of targets can be generated through mutagenesis of Sso7d and
      other hyperthermophilic proteins. Therefore, our approach may be broadly relevant
      to cases where capture of large multivalent species from complex mixtures and
      subsequent release without the use of harsh elution conditions is necessary.

PMID- 23125178
TI  - Proteomics of nonmodel plant species.
AB  - Until recently, large scale proteomic investigations in the plant field have only
      been possible for a few model species for which the whole genome sequence had
      been fully determined. In contrast, for many other species with a strong economic
      interest as sources of human food and animal feed, as well as industrial and
      pharmacological molecules, little was known about their genome sequence and
      identifying the proteome in these species was still considered challenging.
      However, progress has been made as a result of several recent advances in
      proteomics tools, e.g. in MS technology and data search programs, and the
      increasing availability of genomic and cDNA sequences from various species.
      Moreover, next-generation sequencing technologies now make it possible to rapidly
      determine, at a reasonable cost, the genome or RNA sequence of species not
      currently considered as models, thus considerably expanding the plant sequence
      databases. This review will show how these advances make it possible to identify
      a large set of proteins, even for species for which few sequences are currently
      available.

PMID- 23125179
TI  - TFPI-2 downregulates multidrug resistance protein in 5-FU-resistant human
      hepatocellular carcinoma BEL-7402/5-FU cells.
AB  - Tissue factor pathway inhibitor-2 (TFPI-2) is known to induce apoptosis and to
      suppress tumor metastasis in several types of cancer cells. However, there is
      little known about its reversal effect on chemoresistant tumor cells. This study
      investigated the effect of TFPI-2 in 5-fluorouracil (5-FU)-resistant human
      hepatocellular cancer BEL-7402/5-FU cells in vitro. We constructed TFPI-2
      overexpression BEL-7402/5-FU cell lines and explored resistance index (RI) of 5
      FU, function of the P-glycoprotein (P-gp) efflux pump, and the mRNA and protein
      expression of drug resistance gene, including multidrug resistance gene (MDR1),
      lung-resistance protein (LRP), multidrug resistance-associated protein (MRP1),
      glutathione-S-transferase-pi (GST-pi), excision repair cross-complementing gene 1
      (ERCC1), and p38 phosphorylation. We found that TFPI-2 improved the RI of 5-FU
      and inhibited P-gp function. Western blotting and real-time PCR revealed that
      TFPI-2 also decreased mRNA and protein expression of MDR1, LRP, MRP1, GST-pi, and
      ERCC1, whereas p38 phosphorylation was increased. We considered that TFPI-2
      reduces 5-FU resistance in BEL-7402/5-FU cells, and the mechanism appears to
      involve p38-mediated downregulation of drug resistance gene expression such as
      MDR1, LRP, MRP1, GST-pi, and ERCC1.

PMID- 23125180
TI  - Cross-species transcriptomic analysis of mouse and rat lung exposed to
      chloroprene.
AB  - beta-Chloroprene (2-chloro-1,3-butadiene), a monomer used in the production of
      neoprene elastomers, is of regulatory interest due to the production of
      multiorgan tumors in mouse and rat cancer bioassays. A significant increase in
      female mouse lung tumors was observed at the lowest exposure concentration of
      12.8 ppm, whereas a small, but not statistically significant increase was
      observed in female rats only at the highest exposure concentration of 80 ppm. The
      metabolism of chloroprene results in the generation of reactive epoxides, and the
      rate of overall chloroprene metabolism is highly species dependent. To identify
      potential key events in the mode of action of chloroprene lung tumorigenesis,
      dose-response and time-course gene expression microarray measurements were made
      in the lungs of female mice and female rats. The gene expression changes were
      analyzed using both a traditional ANOVA approach followed by pathway enrichment
      analysis and a pathway-based benchmark dose (BMD) analysis approach. Pathways
      related to glutathione biosynthesis and metabolism were the primary pathways
      consistent with cross-species differences in tumor incidence. Transcriptional BMD
      values for the pathway were more similar to differences in tumor response than
      were estimated target tissue dose surrogates based on the total amount of
      chloroprene metabolized per unit mass of lung tissue per day. The closer
      correspondence of the transcriptional changes with the tumor response is likely
      due to their reflection of the overall balance between metabolic activation and
      detoxication reactions, whereas the current tissue dose surrogate reflects only
      oxidative metabolism.

PMID- 23125181
TI  - Organized plasmonic clusters with high coordination number and extraordinary
      enhancement in surface-enhanced Raman scattering (SERS).

PMID- 23125182
TI  - Production and scale-up of a monoclonal antibody against 17-hydroxyprogesterone.
AB  - The hybridoma 192 was used to produce a monoclonal antibody (MAb) against 17
      hydroxyprogesterone (17-OHP), for possible use in screening for congenital
      adrenal hyperplasia (CAH). The factors influencing the MAb production were
      screened and optimized in a 2 L stirred bioreactor. The production was then
      scaled up to a 20 L bioreactor. All of the screened factors (aeration rate,
      stirring speed, dissolved oxygen concentration, pH, and temperature) were found
      to significantly affect production. Optimization using the response surface
      methodology identified the following optimal production conditions: 36.8 degrees
      C, pH 7.4, stirring speed of 100 rpm, 30% dissolved oxygen concentration, and an
      aeration rate of 0.09 vvm. Under these conditions, the maximum viable cell
      density achieved was 1.34 +/- 0.21 * 10(6) cells mL(-1) and the specific growth
      rate was 0.036 +/- 0.004 h(-1) . The maximum MAb titer was 11.94 +/- 4.81 MUg mL(
      1) with an average specific MAb production rate of 0.273 +/- 0.135 pg cell(-1) h(
      1) . A constant impeller tip speed criterion was used for the scale-up. The
      specific growth rate (0.040 h(-1) ) and the maximum viable cell density (1.89 *
      10(6) cells mL(-1) ) at the larger scale were better than the values achieved at
      the small scale, but the MAb titer in the 20 L bioreactor was 18% lower than in
      the smaller bioreactor. A change in the culture environment from the static
      conditions of a T-flask to the stirred bioreactor culture did not affect the
      specificity of the MAb toward its antigen (17-OHP) and did not compromise the
      structural integrity of the MAb.

PMID- 23125184
TI  - Integration of phosphoproteomic, chemical, and biological strategies for the
      functional analysis of targeted protein phosphorylation.
AB  - Reversible phosphorylation, tightly controlled by protein kinases and
      phosphatases, plays a central role in mediating biological processes, such as
      protein-protein interactions, subcellular translocation, and activation of
      cellular enzymes. MS-based phosphoproteomics has now allowed the detection and
      quantification of tens of thousands of phosphorylation sites from a typical
      biological sample in a single experiment, which has posed new challenges in
      functional analysis of each and every phosphorylation site on specific signaling
      phosphoproteins of interest. In this article, we review recent advances in the
      functional analysis of targeted phosphorylation carried out by various chemical
      and biological approaches in combination with the MS-based phosphoproteomics.
      This review focuses on three types of strategies, including forward functional
      analysis, defined for the result-driven phosphoproteomics efforts in determining
      the substrates of a specific protein kinase; reverse functional analysis, defined
      for tracking the kinase(s) for specific phosphosite(s) derived from the discovery
      driven phosphoproteomics efforts; and MS-based analysis on the structure-function
      relationship of phosphoproteins. It is expected that this review will provide a
      state-of-the-art overview of functional analysis of site-specific phosphorylation
      and explore new perspectives and outline future challenges.

PMID- 23125185
TI  - Lysosome dysfunction enhances oxidative stress-induced apoptosis through
      ubiquitinated protein accumulation in Hela cells.
AB  - The role of lysosomal system in oxidative stress-induced apoptosis in cancer
      cells is not fully understood. Menadione is frequently used as oxidative stress
      model. It is indicated that menadione could induce autophagy in Hela cells. In
      the present study, we examined whether the lysosomal inhibitor, ammonium chloride
      (NH(4)Cl) could prevent the autophagy flux by inhibiting the fusion of
      autophagosomes with lysosomes and enhance apoptosis induced by menadione via
      mitochondrial pathway. The results demonstrated generation and accumulation of
      reactive oxygen species and increased levels of ubiquitinated proteins and GRP78
      in cells treated with both menadione and NH(4)Cl. Our data indicates that
      lysosomal system through autophagy plays an important role in preventing
      menadione-induced apoptosis in Hela cells by clearing misfolded proteins, which
      alleviates endoplasmic reticulum stress.

PMID- 23125183
TI  - Acid extrusion via blood-brain barrier causes brain alkalosis and seizures after
      neonatal asphyxia.
AB  - Birth asphyxia is often associated with a high seizure burden that is predictive
      of poor neurodevelopmental outcome. The mechanisms underlying birth asphyxia
      seizures are unknown. Using an animal model of birth asphyxia based on 6-day-old
      rat pups, we have recently shown that the seizure burden is linked to an increase
      in brain extracellular pH that consists of the recovery from the asphyxia-induced
      acidosis, and of a subsequent plateau level well above normal extracellular pH.
      In the present study, two-photon imaging of intracellular pH in neocortical
      neurons in vivo showed that pH changes also underwent a biphasic acid-alkaline
      response, resulting in an alkaline plateau level. The mean alkaline overshoot was
      strongly suppressed by a graded restoration of normocapnia after asphyxia. The
      parallel post-asphyxia increase in extra- and intracellular pH levels indicated a
      net loss of acid equivalents from brain tissue that was not attributable to a
      disruption of the blood-brain barrier, as demonstrated by a lack of increased
      sodium fluorescein extravasation into the brain, and by the electrophysiological
      characteristics of the blood-brain barrier. Indeed, electrode recordings of pH in
      the brain and trunk demonstrated a net efflux of acid equivalents from the brain
      across the blood-brain barrier, which was abolished by the Na/H exchange
      inhibitor, N-methyl-isobutyl amiloride. Pharmacological inhibition of Na/H
      exchange also suppressed the seizure activity associated with the brain-specific
      alkalosis. Our findings show that the post-asphyxia seizures are attributable to
      an enhanced Na/H exchange-dependent net extrusion of acid equivalents across the
      blood-brain barrier and to consequent brain alkalosis. These results suggest
      targeting of blood-brain barrier-mediated pH regulation as a novel approach in
      the prevention and therapy of neonatal seizures.

PMID- 23125186
TI  - Comparative analysis of heterologous expression, biochemical characterization
      optimal production of an alkaline alpha-amylase from alkaliphilic Alkalimonas
      amylolytica in Escherichia coli and Pichia pastoris.
AB  - An alkaline alpha-amylase gene from alkaliphilic Alkalimonas amylolytica was
      synthesized based on the preferred codon usage of Escherichia coli and Pichia
      pastoris, respectively, and then was expressed in the according heterologous
      host, E. coli BL21 (DE3) and P. pastoris GS115. The alkaline alpha-amylase
      expressed in E. coli was designated AmyA, whereas that produced by P. pastoris
      was designated AmyB. The specific activity of AmyA and AmyB was 16.0 and 16.6
      U/mg at pH 9.5 and 50 degrees C, respectively. The optimal pH and pH stability of
      AmyA and AmyB were similar, whereas the optimum temperature and thermal stability
      of AmyB were slightly enhanced compared with those of AmyA. The AmyA and AmyB had
      a similar melting temperature of 64 degrees C and the same catalytic efficiency
      (k(cat) /K(m) ) of 2.0 * 10(6) L/(mol min). AmyA and AmyB were slightly activated
      by 1 mM Co(2+) , Ca(2+) , or Na(+) , but inhibited by all other metal ions (K(+)
      , Mg(2+) , Fe(3+) , Fe(2+) , Zn(2+) , Mn(2+) , and Cu(2+) ). Tween 80 or Tween 60
      (10% (w/v)) had little influence on the stability of AmyA and AmyB, while the 10%
      (w/v) sodium dodecyl sulfate caused the complete loss of AmyA and AmyB
      activities. The AmyA and AmyB were stable in the presence of solid detergents
      (washing powder), while were less stable in liquid detergents. Under the optimal
      conditions in 3-L bioreactor, the extracellular AmyB activity reached 600 U/mL,
      which was about 10 times as that of AmyA. These results indicated that P.
      pastoris was a preferable host for alkaline alpha-amylase expression and the
      produced alkaline alpha-amylase had a certain application potential in solid
      detergents.

PMID- 23125187
TI  - Hydrogenation of a rhodium peroxido complex by formate derivatives: mechanistic
      studies and the catalytic formation of H2O2 from O2.
AB  - Hydrogenation of dioxygen: The rhodium peroxido complex 1, which can be prepared
      from 2 and dioxygen, can be reduced with dihydrogen sources to yield hydrogen
      peroxide. In a catalytic experiment, hydrogen peroxide is produced from dioxygen
      and ammonium formate under ambient conditions in the presence of 1 (see scheme).

PMID- 23125190
TI  - Fed-batch CHO cell t-PA production and feed glutamine replacement to reduce
      ammonia production.
AB  - Industrial therapeutic protein production has been greatly improved through fed
      batch development. In this study, improvement to the productivity of a tissue
      plasminogen activator (t-PA) expressing Chinese hamster ovary (CHO) cell line was
      investigated in shake flask culture through the optimization of the fed-batch
      feed and the reduction of ammonia generation by glutamine replacement. The t-PA
      titer was increased from 33 mg/L under batch conditions to 250 mg/L with daily
      feeding starting after three days of culture. A commercially available fed-batch
      feed was supplemented with cotton seed hydrolysate and the four depleted amino
      acids, aspartic acid, asparagine, cysteine, and tyrosine. The fed-batch operation
      increased the generation of by-products such as lactate and ammonia that can
      adversely affect the fed-batch performance. To reduce the ammonia production, a
      glutamine-containing dipeptide, pyruvate, glutamate, and wheat gluten
      hydrolysate, were investigated as glutamine substitutes. To minimize the lag
      phase as the cells adjusted to the new energy source, a feed glutamine
      replacement process was developed where the cells were initially cultured with a
      glutamine containing basal medium to establish cell growth followed by feeding
      with a feed containing the glutamine substitutes. This two-step feed glutamine
      replacement process not only reduced the ammonia levels by over 45% but, in the
      case of using wheat gluten hydrolysate, almost doubled the t-PA titer to over 420
      mg/L without compromising the t-PA product quality or glycosylation pattern. The
      feed glutamine replacement process combined with optimizing other feed medium
      components provided a simple, practical, and effective fed-batch strategy that
      could be applied to the production of other recombinant therapeutic proteins.

PMID- 23125192
TI  - Solubility properties and diffusional extraction behavior of natamycin from
      Streptomyces gilvosporeus biomass.
AB  - Natamycin is a type of polyene macrolide antibiotic and has been produced in
      submerged microbial cultures of some natural Streptomyces strains. Natamycin
      extraction from cellular biomass is greatly affected by the molecular and
      solubilization characteristics of the extraction solvent, and this is a major
      reason for the routine attainment of low volumetric titers, resulting from
      sparing natamycin solubility. In this work, a series of experiments were
      conducted to investigate the solubility of natamycin in some selected organic
      solvents in order to assess the influence on natamycin extraction yield.
      Natamycin showed the highest solubility in 75% aqueous methanol under the
      conditions of pH 2, 30 degrees C and 1 atm. Furthermore, the extraction of
      natamycin using 75% aqueous methanol was performed and the highest extraction
      yield of 45.7% was obtained under pH 2. A mathematical model derived from Fick's
      law of the biomolecular diffusion process was developed to fit the experimental
      kinetic data of natamycin extraction.

PMID- 23125191
TI  - Targeting C4-demethylating genes in the cholesterol pathway sensitizes cancer
      cells to EGF receptor inhibitors via increased EGF receptor degradation.
AB  - Persistent signaling by the oncogenic EGF receptor (EGFR) is a major source of
      cancer resistance to EGFR targeting. We established that inactivation of 2 sterol
      biosynthesis pathway genes, SC4MOL (sterol C4-methyl oxidase-like) and its
      partner, NSDHL (NADP-dependent steroid dehydrogenase-like), sensitized tumor
      cells to EGFR inhibitors. Bioinformatics modeling of interactions for the sterol
      pathway genes in eukaryotes allowed us to hypothesize and then extensively
      validate an unexpected role for SC4MOL and NSDHL in controlling the signaling,
      vesicular trafficking, and degradation of EGFR and its dimerization partners,
      ERBB2 and ERBB3. Metabolic block upstream of SC4MOL with ketoconazole or CYP51A1
      siRNA rescued cancer cell viability and EGFR degradation. Inactivation of SC4MOL
      markedly sensitized A431 xenografts to cetuximab, a therapeutic anti-EGFR
      antibody. Analysis of Nsdhl-deficient Bpa(1H/+) mice confirmed dramatic and
      selective loss of internalized platelet-derived growth factor receptor in
      fibroblasts, and reduced activation of EGFR and its effectors in regions of skin
      lacking NSDHL. SIGNIFICANCE: This work identifies a critical role for SC4MOL and
      NSDHL in the regulation of EGFR signaling and endocytic trafficking and suggests
      novel strategies to increase the potency of EGFR antagonists in tumors.

PMID- 23125193
TI  - Identification of small molecule inhibitors of cytokinesis and single cell wound
      repair.
AB  - Screening of small molecule libraries offers the potential to identify compounds
      that inhibit specific biological processes and, ultimately, to identify
      macromolecules that are important players in such processes. To date, however,
      most screens of small molecule libraries have focused on identification of
      compounds that inhibit known proteins or particular steps in a given process, and
      have emphasized automated primary screens. Here we have used "low tech" in vivo
      primary screens to identify small molecules that inhibit both cytokinesis and
      single cell wound repair, two complex cellular processes that possess many common
      features. The "diversity set", an ordered array of 1990 compounds available from
      the National Cancer Institute, was screened in parallel to identify compounds
      that inhibit cytokinesis in Dendraster excentricus (sand dollar) embryos and
      single cell wound repair in Xenopus laevis (frog) oocytes. Two small molecules
      were thus identified: Sph1 and Sph2. Sph1 reduces Rho activation in wound repair
      and suppresses formation of the spindle midzone during cytokinesis. Sph2 also
      reduces Rho activation in wound repair and may inhibit cytokinesis by blocking
      membrane fusion. The results identify two small molecules of interest for
      analysis of wound repair and cytokinesis, reveal that these processes are more
      similar than often realized and reveal the potential power of low tech screens of
      small molecule libraries for analysis of complex cellular processe.

PMID- 23125194
TI  - Common mechanisms regulating cell cortex properties during cell division and cell
      migration.
AB  - Single cell morphogenesis results from a balance of forces involving internal
      pressure (also called turgor pressure in plants and fungi) and the plastic and
      dynamic outer shell of the cell. Dominated by the cell wall in plants and fungi,
      mechanical properties of the outer shell of animal cells arise from the cell
      cortex, which is mostly composed of the plasma membrane (and membrane proteins)
      and the underlying meshwork of actin filaments and myosin motors (and associated
      proteins). In this review, following Bray and White [1988; Science 239:883-889],
      we draw a parallel between the regulation of the cell cortex during cell division
      and cell migration in animal cells. Starting from the similarities in shape
      changes and underlying mechanical properties, we further propose that the analogy
      between cell division and cell migration might run deeper, down to the basic
      molecular mechanisms driving cell cortex remodeling. We focus our attention on
      how an heterogeneous and dynamic cortex can be generated to allow cell shape
      changes while preserving cell integrity.

PMID- 23125195
TI  - Evidence for effects of manufactured nanomaterials on crops is inconclusive.

PMID- 23125196
TI  - A zoo of computable binary normal sequences.
AB  - Historically there has been a virtual absence of constructive methods to produce
      broad classes of "certifiably random" infinite sequences, despite considerable
      interest in this endeavor. Previously, we proved a theorem that yielded explicit
      algorithms to produce diverse sets of normal numbers, reasonable candidates for
      random sequences, given their limiting equidistribution of subblocks of all
      lengths. Herein, we develop this algorithmic approach much further, systematizing
      the normal number generation process in several ways. We construct delineated,
      distinct sets of normal numbers (classified by the extent to which initial
      segments deviate from maximal irregularity), with virtually any allowable
      specified rate of convergence to 0 of this deviation, encompassing arbitrarily
      fast and slow rates, and accommodating asymmetric behavior above or below a
      centered median. As a corollary, we provide an explicit construction of a normal
      number that satisfies the Law of the Iterated Logarithm. We also produce distinct
      families of "biased" normal numbers, with virtually any specified rate of
      convergence of the bias (to 0). This latter theory is in part motivated by the
      remarkable observation that the binary version of Champernowne's number, which is
      also normal, is biased-any initial segment has more 1s than 0s. Finally, we
      construct an interesting normal sequence with arbitrarily fast convergence to
      equidistribution of singleton blocks, yet arbitrarily slow convergence of pairs,
      which has profound implications both for probability theory, and for metrics to
      evaluate the "near-randomness" of sequences.

PMID- 23125197
TI  - Common polymorphisms in angiogenesis.
AB  - A wide variety of diseases have a significant genetic component, including major
      causes of morbidity and mortality in the western world. Many of these diseases
      are also angiogenesis dependent. In humans, common polymorphisms, although more
      subtle in effect than rare mutations that cause Mendelian disease, are expected
      to have greater overall effects on human disease. Thus, common polymorphisms in
      angiogenesis-regulating genes may affect the response to an angiogenic stimulus
      and thereby affect susceptibility to or progression of such diseases. Candidate
      gene studies have identified several associations between angiogenesis gene
      polymorphisms and disease. Similarly, emerging pharmacogenomic evidence indicates
      that several angiogenesis-regulating polymorphisms may predict response to
      therapy. In contrast, genome-wide association studies have identified only a few
      risk alleles in obvious angiogenesis genes. As in other traits, regulatory
      polymorphisms appear to dominate the landscape of angiogenic responsiveness.
      Rodent assays, including the mouse corneal micropocket assay, tumor models, and a
      macular degeneration model have allowed the identification and comparison of loci
      that directly affect the trait. Complementarity between human and animal
      approaches will allow increased understanding of the genetic basis for
      angiogenesis-dependent disease.

PMID- 23125200
TI  - Supramolecular dynamics of mucus.
AB  - Our purpose here is not to address specific issues of mucus pathology, but to
      illustrate how polymer networks theory and its remarkable predictive power can be
      applied to study the supramolecular dynamics of mucus. Avoiding unnecessary
      mathematical formalization, in the light of available theory, we focus on the
      rather slow progress and the still large number of missing gaps in the complex
      topology and supramolecular dynamics of airway mucus. We start with the limited
      information on the polymer physics of respiratory mucins to then converge on the
      supramolecular organization and resulting physical properties of the mucus gel.
      In each section, we briefly discuss progress on the subject, the uncertainties
      associated with the established knowledge, and the many riddles that still
      remain.

PMID- 23125198
TI  - Angiogenic factors in preeclampsia and related disorders.
AB  - During fetal development, the human placenta undergoes high levels of both
      angiogenesis and vasculogenesis. Additionally, the developing placenta undergoes
      a process of vascular mimicry (referred to as pseudovasculogenesis) as
      cytotrophoblasts convert from an epithelial to an endothelial phenotype. The
      initiation, maturation, and maintenance of the placental vasculature are of
      critical importance. Failure to do so can lead to adverse obstetric outcomes such
      as preeclampsia and/or intrauterine growth restriction (IUGR). Furthermore, the
      foundation of many aspects of adult health is laid in utero. In this context,
      normal placental function is not only critical for normal fetal development but
      can also permanently influence long-term health and disease. Understanding the
      mechanisms that regulate placental vasculogenesis and angiogenesis is therefore
      of critical importance. This chapter will focus on placental vascular development
      with a particular emphasis on the role of angiogenic factors in the pathogenesis
      of the maternal syndrome of preeclampsia and related disorders.

PMID- 23125199
TI  - The pathogenesis and natural history of type 1 diabetes.
AB  - The purpose of this article is to provide an overview that summarizes much in the
      way of our current state of knowledge regarding the pathogenesis and natural
      history of type 1 diabetes in humans. This information is presented to the reader
      as a series of seminal historical discoveries that, when advanced through
      research, transformed our understanding of the roles for the immune system,
      genes, and environment in the formation of this disease. In addition, where
      longitudinal investigations of these three facets occurred, their roles within
      the development of type 1 diabetes, from birth to symptomatic onset and beyond,
      are discussed, including their most controversial elements. Having an
      understanding of this disorder's pathogenesis and natural history is key for
      attempts seeking to understand the issues of what causes type 1 diabetes, as well
      as to develop a means to prevent and cure the disorder.

PMID- 23125201
TI  - Entry of Listeria monocytogenes in mammalian epithelial cells: an updated view.
AB  - Listeria monocytogenes is a bacterial pathogen that promotes its internalization
      into host epithelial cells. Interaction between the bacterial surface molecules
      InlA and InlB and their cellular receptors E-cadherin and Met, respectively,
      triggers the recruitment of endocytic effectors, the subversion of the
      phosphoinositide metabolism, and the remodeling of the actin cytoskeleton that
      lead to bacterial engulfment. Additional bacterial surface and secreted virulence
      factors also contribute to entry, albeit to a lesser extent. Here we review the
      increasing number of signaling effectors that are reported as being subverted by
      L. monocytogenes during invasion of cultured cell lines. We also update the
      current knowledge of the early steps of in vivo cellular infection, which, as
      shown recently, challenges previous concepts generated from in vitro data.

PMID- 23125202
TI  - Alzheimer disease in 2020.
AB  - Remarkable advances in unraveling the biological underpinnings of Alzheimer
      disease (AD) have occurred during the last 25 years. Despite this, we have made
      only the smallest of dents in the development of truly disease-modifying
      treatments. What will change over the next 10 years? While the answer is not
      clear, we make several predictions on the state of the field in 2020, based on
      the rich knowledge described in the other contributions in this collection. As
      such, our predictions represent some of the principal unresolved questions that
      we believe deserve special investigative attention in the coming decade.

PMID- 23125203
TI  - Development of gene therapy for thalassemia.
AB  - Retroviral vector-mediated gene transfer into hematopoietic stem cells provides a
      potentially curative therapy for severe beta-thalassemia. Lentiviral vectors
      based on human immunodeficiency virus have been developed for this purpose and
      have been shown to be effective in curing thalassemia in mouse models. One
      participant in an ongoing clinical trial has achieved transfusion independence
      after gene transfer into bone marrow stem cells owing, in part, to a genetically
      modified, dominant clone. Ongoing efforts are focused on improving the efficiency
      of lentiviral vector-mediated gene transfer into stem cells so that the curative
      potential of gene transfer can be consistently achieved.

PMID- 23125204
TI  - Responses to novelty and vulnerability to cocaine addiction: contribution of a
      multi-symptomatic animal model.
AB  - Epidemiological studies have revealed striking associations between several
      distinct behavioral/personality traits and drug addiction, with a large emphasis
      on the sensation-seeking trait and the associated impulsive dimension of
      personality. However, in human studies, it is difficult to identify whether
      personality/behavioral traits actually contribute to increased vulnerability to
      drug addiction or reflect psychobiological adaptations to chronic drug exposure.
      Here we show how animal models, including the first multi-symptomatic model of
      addiction in the rat, have contributed to a better understanding of the
      relationships between different subdimensions of the sensation-seeking trait and
      different stages of the development of cocaine addiction, from vulnerability to
      initiation of cocaine self-administration to the transition to compulsive drug
      intake. We argue that sensation seeking predicts vulnerability to use cocaine,
      whereas novelty seeking, akin to high impulsivity, predicts instead vulnerability
      to shift from controlled to compulsive cocaine use, that is, addiction.

PMID- 23125206
TI  - Perspectives on mucus properties and formation--lessons from the biochemical
      world.
AB  - Our model of the MUC2 mucin shows a well-organized netlike gel that is cross
      linked by six different covalent and noncovalent bonds. When the MUC2 mucin is
      packed in the mucin granule it is organized by an amino-terminal concatenated
      ring platform formed at high calcium and low pH. This packing allows an ordered
      release and a normal mucin expansion when calcium is removed and pH increased by
      bicarbonate. This process is defective in the absence of cystic fibrosis
      transmembrane conductance regulator (CFTR)-dependent bicarbonate transport. The
      expanded secreted mucin is suggested to be self-organizing by properties
      inherited in the MUC2 mucin and by proteolytic processes.

PMID- 23125207
TI  - Discovery of high-confidence single nucleotide polymorphisms from large-scale de
      novo analysis of leaf transcripts of Aegilops tauschii, a wild wheat progenitor.
AB  - Construction of high-resolution genetic maps is important for genetic and genomic
      research, as well as for molecular breeding. Single nucleotide polymorphisms
      (SNPs) are the predominant class of genetic variation and can be used as
      molecular markers. Aegilops tauschii, the D-genome donor of common wheat, is
      considered a valuable genetic resource for wheat improvement. Our previous study
      implied that Ae. tauschii accessions can be genealogically divided into two major
      lineages. In this study, the transcriptome of two Ae. tauschii accessions from
      each lineage, lineage 1 (L1) and 2 (L2), was sequenced, yielding 9435 SNPs and
      739 insertion/deletion polymorphisms (indels) after de novo assembly of the
      reads. Based on 36 contig sequences, 31 SNPs and six indels were validated on 20
      diverse Ae. tauschii accessions. Because almost all of the SNP markers were
      polymorphic between L1 and L2, and the D-genome donor of common wheat is presumed
      to belong to L2, these markers are available for D-genome typing in crosses
      between common wheat varieties and L1-derived synthetic wheat. Due to the
      conserved synteny between wheat and barley chromosomes, the high-density
      expressed sequence tag barley map and the hypothetical gene order in barley can
      be applied to develop markers on target chromosomal regions in wheat.

PMID- 23125205
TI  - Bacterial quorum sensing: its role in virulence and possibilities for its
      control.
AB  - Quorum sensing is a process of cell-cell communication that allows bacteria to
      share information about cell density and adjust gene expression accordingly. This
      process enables bacteria to express energetically expensive processes as a
      collective only when the impact of those processes on the environment or on a
      host will be maximized. Among the many traits controlled by quorum sensing is the
      expression of virulence factors by pathogenic bacteria. Here we review the quorum
      sensing circuits of Staphylococcus aureus, Bacillus cereus, Pseudomonas
      aeruginosa, and Vibrio cholerae. We outline these canonical quorum-sensing
      mechanisms and how each uniquely controls virulence factor production.
      Additionally, we examine recent efforts to inhibit quorum sensing in these
      pathogens with the goal of designing novel antimicrobial therapeutics.

PMID- 23125208
TI  - A novel hemoglobin-binding peptide reduces cell-free hemoglobin in murine
      hemolytic anemia.
AB  - Hemolysis can saturate the hemoglobin (Hb)/heme scavenging system, resulting in
      increased circulating cell-free Hb (CF-Hb) in hereditary and acquired hemolytic
      disease. While recent studies have suggested a central role for intravascular
      hemolysis and CF-Hb in the development of vascular dysfunction, this concept has
      stimulated considerable debate. This highlights the importance of determining the
      contribution of CF-Hb to vascular complications associated with hemolysis.
      Therefore, a novel Hb-binding peptide was synthesized and linked to a small
      fragment of apolipoprotein E (amino acids 141-150) to facilitate endocytic
      clearance. Plasma clearance of hE-Hb-b10 displayed a rapid phase t(1/2) of 16 min
      and slow phase t(1/2) of 10 h, trafficking primarily through the liver. Peptide
      hE-Hb-B10 decreased CF-Hb in mice treated with phenylhydrazine, a model of acute
      hemolysis. Administration of hE-Hb-B10 also attenuated CF-Hb in two models of
      chronic hemolysis: Berkeley sickle cell disease (SS) mice and mice with severe
      hereditary spherocytosis (HS). The hemolytic rate was unaltered in either chronic
      hemolysis model, supporting the conclusion that hE-Hb-B10 promotes CF-Hb
      clearance without affecting erythrocyte lysis. Interestingly, hE-Hb-B10 also
      decreased plasma ALT activity in SS and HS mice. Although acetylcholine-mediated
      facialis artery vasodilation was not improved by hE-Hb-B10 treatment, the peptide
      shifted vascular response in favor of NO-dependent vasodilation in SS mice. Taken
      together, these data demonstrate that hE-Hb-B10 decreases CF-Hb with a
      concomitant reduction in liver injury and changes in vascular response.
      Therefore, hE-Hb-B10 can be used to investigate the different roles of CF-Hb in
      hemolytic pathology and may have therapeutic benefit in the treatment of CF-Hb
      mediated tissue damage.

PMID- 23125209
TI  - Antisickling fetal hemoglobin reduces hypoxia-inducible factor-1alpha expression
      in normoxic sickle mice: microvascular implications.
AB  - Chronic inflammation is a salient feature of sickle cell disease (SCD) and
      transgenic-knockout sickle (BERK) mice. Inflammation is implicated in the
      activation of hypoxia-inducible factor-1alpha (HIF-1alpha) under normoxic
      conditions. We hypothesize that, in SCD, inflammation coupled with nitric oxide
      (NO) depletion will induce expression of HIF-1alpha, a transcription factor with
      wide-ranging effects including activation of genes for vasoactive molecules. To
      this end, we have examined the expression of HIF-1alpha in normoxic BERK mice
      expressing exclusively human alpha- and beta(S)- globins, and evaluated the
      effect of fetal hemoglobin (HbF) in BERK mice (i.e., <1.0%, 20%, and 40% HbF).
      HbF exerts antisickling and anti-inflammatory effects. Here, we show that HIF
      1alpha is expressed in BERK mice under normoxic conditions, accompanied by
      increased expression of its vasoactive biomarkers such as VEGF, heme oxygenase-1
      (HO-1), and serum ET-1 levels. In BERK mice expressing HbF, HIF-1alpha expression
      decreases concomitantly with increasing HbF, commensurately with increased NO
      bioavailability, and shows a strong inverse correlation with plasma NO
      metabolites (NOx) levels. Reduced HIF-1alpha expression is associated with
      decreased HO-1, VEGF, and ET-1. Notably, arteriolar dilation, enhanced volumetric
      blood flow, and low blood pressure in normoxic BERK mice all show a trend toward
      normalization with the introduction of HbF. Also, arginine treatment reduced HIF
      1alpha, as well as VEGF expression in normoxic BERK mice, supporting a role of NO
      bioavailability in HIF-1alpha activation. Thus HIF-1alpha expression in normoxic
      sickle mice is likely a consequence of chronic inflammation, and HbF exerts an
      ameliorating effect by decreasing sickling, increasing NO bioavailability, and
      reducing inflammation.

PMID- 23125210
TI  - Construction of two novel reciprocal conplastic rat strains and characterization
      of cardiac mitochondria.
AB  - Because of the lack of appropriate animal models, the potentially causal
      contributions of inherited mitochondrial genomic factors to complex traits are
      less well studied compared with inherited nuclear genomic factors. We previously
      detected variations between the mitochondrial DNA (mtDNA) of the Dahl salt
      sensitive (S) rat and the spontaneously hypertensive rat (SHR). Specifically,
      multiple variations were detected in mitochondrial genes coding for subunits of
      proteins essential for electron transport, in mitochondrial reactive oxygen
      species production, and within the D-loop region. To evaluate the effects of
      these mtDNA variations in the absence of the corresponding nuclear genomic
      factors as confounding variables, novel reciprocal strains of S and SHR were
      constructed and characterized. When compared with that of the S rat, the heart
      tissue from the S.SHR(mt) conplastic strain wherein the mtDNA of the S rat was
      substituted with that of the SHR had a significant increase in mtDNA copy number
      and decrease in mitochondrial reactive oxygen species production. A corresponding
      increase in aerobic treadmill running capacity and a significant increase in
      survival that was not related to changes in blood pressure were observed in the
      S.SHR(mt) rats compared with the S rat. The reciprocal SHR.S(mt) rats did not
      differ from the SHR in any phenotype tested, suggesting lower penetrance of the S
      mtDNA on the nuclear genomic background of the SHR. These novel conplastic
      strains serve as invaluable tools to further dissect the relationship between
      heart function, aerobic fitness, cardiovascular disease progression, and
      mortality.

PMID- 23125211
TI  - Hibernating myocardium results in partial sympathetic denervation and nerve
      sprouting.
AB  - Hibernating myocardium due to chronic repetitive ischemia is associated with
      regional sympathetic nerve dysfunction and spontaneous arrhythmic death in the
      absence of infarction. Although inhomogeneity in regional sympathetic innervation
      is an acknowledged substrate for sudden death, the mechanism(s) responsible for
      these abnormalities in viable, dysfunctional myocardium (i.e., neural stunning
      vs. sympathetic denervation) and their association with nerve sprouting are
      unknown. Accordingly, markers of sympathetic nerve function and nerve sprouting
      were assessed in subendocardial tissue collected from chronically instrumented
      pigs with hibernating myocardium (n = 18) as well as sham-instrumented controls
      (n = 7). Hibernating myocardium exhibited evidence of partial sympathetic
      denervation compared with the normally perfused region and sham controls, with
      corresponding regional reductions in tyrosine hydroxylase protein (-32%, P <
      0.001), norepinephrine uptake transport protein (-25%, P = 0.01), and tissue
      norepinephrine content (-45%, P < 0.001). Partial denervation induced nerve
      sprouting with regional increases in nerve growth factor precursor protein (31%,
      P = 0.01) and growth associated protein-43 (38%, P < 0.05). All of the changes in
      sympathetic nerve markers were similar in animals that developed sudden death (n
      = 9) compared with electively terminated pigs with hibernating myocardium (n =
      9). In conclusion, sympathetic nerve dysfunction in hibernating myocardium is
      most consistent with partial sympathetic denervation and is associated with
      regional nerve sprouting. The extent of sympathetic remodeling is similar in
      animals that develop sudden death compared with survivors; this suggests that
      sympathetic remodeling in hibernating myocardium is not an independent trigger
      for sudden death. Nevertheless, sympathetic remodeling likely contributes to
      electrical instability in combination with other factors.

PMID- 23125212
TI  - An angiogenesis model for investigating multicellular interactions across intact
      microvascular networks.
AB  - Developing therapies aimed at manipulating microvascular remodeling requires a
      better understanding of angiogenesis and how angiogenesis relates to other
      network remodeling processes, such as lymphangiogenesis and neurogenesis. The
      objective of this study was to develop an angiogenesis model that enables probing
      of multicellular and multisystem interactions at the molecular level across an
      intact adult microvascular network. Adult male Wistar rat mesenteric windows were
      aseptically harvested and cultured in serum-free minimum essential media.
      Viability/cytotoxicity analysis revealed that cells remain alive for at least 7
      days. Immunohistochemical labeling at 3 days for platelet endothelial cell
      adhesion molecule (PECAM), neuron-glial antigen 2 (NG2), lymphatic vessel
      endothelial hyaluronan receptor-1 (LYVE-1), and class III beta-tubulin identified
      endothelial cells, pericytes, lymphatics, and nerves, respectively. Media
      supplemented with bFGF or VEGF induced an increase in endothelial cell sprouting
      off existing vessels. Endothelial cell sprouting in both growth factor groups was
      inhibited by targeting pericytes with NG2 functional blocking antibody. VEGF
      caused an increase in the number of lymphatic/blood endothelial cell connections
      compared with media alone or bFGF groups. Finally, the comparison of the same
      network before and after angiogenesis stimulated by the supplement of media with
      20% serum identified the ability of disconnected endothelial segments to
      reconnect to nearby vessels. The results establish a novel in situ angiogenesis
      model for investigating the location of capillary sprouting within an intact
      network, the role of pericytes, lymphatic/blood endothelial cell interactions,
      and the fate of specific endothelial cell segments. The rat mesentery culture
      system offers a unique tool for understanding the complex dynamics associated
      with angiogenesis in an intact adult tissue.

PMID- 23125213
TI  - Vascular dysfunction in young, mid-aged and aged mice with latent cytomegalovirus
      infections.
AB  - Human cytomegalovirus (HCMV) is associated with vascular diseases in both
      immunosuppressed and immunocompetent individuals. CMV infections cycle between
      active and latent phases throughout life. We and others have shown vascular
      dysfunction during active mouse CMV (mCMV) infections. Few studies have examined
      changes in physiology during latent CMV infections, particularly vascular
      responses or whether the negative effects of aging on vascular function and
      fertility will be exacerbated under these conditions. We measured vascular
      responses in intact mesenteric and uterine arteries dissected from young, mid
      aged, and aged latently mCMV-infected (mCMV genomes are present but infectious
      virus is undetectable) and age-matched uninfected mice using a pressure myograph.
      We tested responses to the alpha(1)-adrenergic agonist phenylephrine, the nitric
      oxide donor sodium nitroprusside, and the endothelium-dependent vasodilator
      methacholine. In young latently mCMV-infected mice, vasoconstriction was
      increased and vasodilation was decreased in mesenteric arteries, whereas both
      vasoconstriction and vasodilation were increased in uterine arteries compared
      with those in age-matched uninfected mice. In reproductively active mid-aged
      latently infected mice, mesenteric arteries showed little change, whereas uterine
      arteries showed greatly increased vasoconstriction. These vascular effects may
      have contributed to the decreased reproductive success observed in mid-aged
      latently mCMV-infected compared with age-matched uninfected mice (16.7 vs. 46.7%,
      respectively). In aged latently infected mice, vasodilation is increased in
      mesenteric and uterine arteries likely to compensate for increased
      vasoconstriction to mediators other than phenylephrine. The novel results of this
      study show that even when active mCMV infections become undetectable, vascular
      dysfunction continues and differs with age and artery origin.

PMID- 23125214
TI  - Relaxant effect of all-trans-retinoic acid via NO-sGC-cGMP pathway and calcium
      activated potassium channels in rat mesenteric artery.
AB  - Intraperitoneal injection of all-trans-retinoic acid (ATRA) results in a
      reduction of blood pressure in spontaneously hypertensive rats. However, the
      mechanisms involved in this effect are not clear. We hypothesized that ATRA may
      relax resistance arteries. In this study, we found that ATRA relaxed
      phenylephrine-preconstricted mesenteric arterial rings, which were abrogated by
      the removal of the endothelium. Pretreatment of endothelium-intact arterial rings
      with an inhibitor of endothelial nitric oxide (NO) synthase, N(G)-nitro-l
      arginine methyl ester (l-NAME), or soluble guanylyl cyclase, 1H-[1,2,4]
      oxadiazole-[4,3-alpha]-quinoxaline-1-one, reduced the vasorelaxant effect of
      ATRA. Incubation of mesenteric arterial rings with ATRA increased the production
      of NO and cGMP, which were blocked by N(G)-nitro-l-arginine methyl ester. The
      vasorelaxant effect of ATRA was markedly attenuated in the presence of an
      inhibitor of big conductance calcium-activated potassium channels
      (charybdotoxin), but not with an inhibitor of voltage-dependent potassium channel
      (4-aminopyridine) or ATP-sensitive potassium channel (glibenclamide). Activation
      of retinoic acid receptors (RARs) with CH55 or retinoic X receptors (RXRs) with
      LGD1069 induced the vasorelaxation of phenylephrine-preconstricted mesenteric
      arterial rings. The RAR (BMS493) and RXR (UVI3003) antagonists blocked the ATRA
      induced vasorelaxation. The vasorelaxant effect ATRA is physiologically relevant
      because the intravenous infusion of ATRA decreased blood pressure in normotensive
      rats. We conclude that ATRA relaxes resistance vessels via both RARs and RXRs
      receptors that are mediated by the endothelium-dependent NO-cGMP pathway, which
      may participate in the control of blood pressure.

PMID- 23125216
TI  - Artery wall layer dimensions during normal pregnancy: a longitudinal study using
      noninvasive high-frequency ultrasound.
AB  - The vascular effects of normal pregnancy were investigated by estimating the
      intima and media thicknesses of the common carotid artery separately using 22-MHz
      ultrasound (Collagenoson, Meudt, Germany) in 57 healthy women with normal
      pregnancies and pregnancy outcomes, in all three trimesters and at 1 yr
      postpartum. A thick intima, thin media, and high intima-to-media (I/M) ratio are
      signs of a less healthy artery wall. Mean artery wall layer dimensions remained
      fairly constant during pregnancy, but the intima thickness and I/M thickness
      ratio appeared to improve (decrease) postpartum (P < 0.001 for both). The
      cardiovascular risk parameters of age, body mass index, and blood pressure in the
      first trimester were associated with higher I/M ratios, especially in the second
      trimester, whereas higher serum estradiol levels were significantly associated
      with a lower I/M ratio. Changes from the first to second trimesters in I/M ratio,
      taking into account differential changes in intima and media thickness, were
      significantly (P < 0.05-0.001) associated with all risk parameters tested except
      age, which was associated with increased intima thickness (P = 0.02).
      Associations with third trimester values and changes from first to third
      trimesters were similar but less apparent. Thus, fairly constant mean artery wall
      layer dimensions during pregnancy appeared to improve postpartum. However, higher
      age, body mass index, or blood pressure and lower serum estradiol levels in the
      first trimester appeared to negatively affect the artery wall, strongly
      suggesting that pregnancy has negative vascular effects in some women. A less
      likely explanation involves possible adaptation to physiological changes during
      and after pregnancy.

PMID- 23125215
TI  - MAP kinase kinase kinase-2 (MEKK2) regulates hypertrophic remodeling of the right
      ventricle in hypoxia-induced pulmonary hypertension.
AB  - Pulmonary hypertension (PH) results in pressure overload of the right ventricle
      (RV) of the heart, initiating pathological RV remodeling and ultimately leading
      to right heart failure. Substantial research indicates that signaling through the
      MAPK superfamily mediates pathological cardiac remodeling. These considerations
      led us to test the hypothesis that the regulatory protein MAPKKK-2 (MEKK2)
      contributes to RV hypertrophy in hypoxia-induced PH. Transgenic mice with global
      knockout of MEKK2 (MEKK2(-/-) mice) and age-matched wild-type (WT) mice were
      exposed to chronic hypobaric hypoxia (10% O(2), 6 wk) and compared with animals
      under normoxia. Exposure to chronic hypoxia induced PH in WT and MEKK2(-/-) mice.
      In response to PH, WT mice showed RV hypertrophy, demonstrated as increased ratio
      of RV weight to body weight, increased RV wall thickness at diastole, and
      increased cardiac myocyte size compared with normoxic control animals. In
      contrast, each of these measures of RV hypertrophy seen in WT mice after chronic
      hypoxia was attenuated in MEKK2(-/-) mice. Furthermore, chronic hypoxia elicited
      altered programs of hypertrophic and inflammatory gene expression consistent with
      pathological RV remodeling in WT mice; MEKK2 deletion selectively inhibited
      inflammatory gene expression compared with WT mice. The actions of MEKK2 were
      mediated in part through regulation of the abundance and phosphorylation of its
      effector, ERK5. In conclusion, signaling by MEKK2 contributes to RV hypertrophy
      and altered myocardial inflammatory gene expression in response to hypoxia
      induced PH. Therapies targeting MEKK2 may protect the myocardium from hypertrophy
      and pathological remodeling in human PH.

PMID- 23125217
TI  - Interleukin-17 induces AP-1 activity and cellular transformation via upregulation
      of tumor progression locus 2 activity.
AB  - Inflammatory conditions elicited by extrinsic environmental factors promote
      malignant transformation, tumor growth and metastasis. Although the role of T
      cells in cancer promotion has been examined, little is known about the underlying
      molecular mechanisms of interleukin-17 A (IL-17A), a proinflammatory cytokine
      produced by activated CD4(+) memory T cells, in carcinogenesis. Here, we report
      that IL-17A induces neoplastic transformation of JB6 Cl41 cells through
      activation of tumor progression locus 2 (TPL2). IL-17A dose- and time-dependently
      increases TPL2 phosphorylation in JB6 Cl41 cells through IL-17A receptor. IL-17A
      activates  mitogen-activated protein kinase/extracellular signal-regulated kinase
      kinases, c-jun N-terminal kinases and STAT3 signaling pathways, which are
      inhibited by a TPL2 kinase inhibitor (TKI). Furthermore, IL-17A activates c-fos
      and c-jun promoter activity, resulting in increased activator protein-1 (AP-1)
      activity. When small interfering RNA of IL-17A receptor (IL-17R), IL-17A and TPL2
      were introduced into JB6 Cl41 cells, respectively, IL-17A-induced AP-1 activity
      was significantly decreased compared with control cells. Similarly, TPL2
      inhibition suppressed AP-1 activity induced by IL-17A. The knockdown of IL-17R
      and TKI treatment in JB6 Cl41 cells resulted in decreased IL-17A-induced cell
      transformation. The in vivo chorioallantoic membrane assay also showed that IL
      17A increased tumor formation of JB6 Cl41 cells, whereas TKI inhibited the
      tumorigenesis promoted by IL-17A. Consistent with these observations, knockdown
      of IL-17A and/or inhibition of TPL2 attenuated tumorigenicity of human breast
      cancer MCF7 cells. Together, our findings point to a critical role for the IL-17A
      induced TPL2 signaling pathway in supporting cancer-associated inflammation in
      the tumor microenvironment. Therapeutic approaches that target this pathway may,
      therefore, effectively inhibit carcinogenesis.

PMID- 23125218
TI  - MicroRNA-152 targets DNA methyltransferase 1 in NiS-transformed cells via a
      feedback mechanism.
AB  - Nickel (Ni) compounds are well-recognized human carcinogens, yet the molecular
      mechanisms by which they cause human cancer are still not well understood.
      MicroRNAs (miRNAs), which are small non-coding RNAs, are involved in diverse
      biological functions and carcinogenesis. In previous study, we identified
      upregulation of DNA methyltransferase 1 (DNMT1) expression in nickel sulfide
      (NiS)-transformed human bronchial epithelial (16HBE) cells. Here, we investigated
      whether some miRNAs are aberrantly expressed and targets DNMT1 in NiS-transformed
      cells. Our results showed that the expression of miRNA-152 (miR-152) was
      specifically downregulated in NiS-transformed cells via promoter DNA
      hypermethylation, whereas ectopic expression of miR-152 in NiS-transformed cells
      resulted in a marked reduction of DNMT1 expression. Further experiments revealed
      that miR-152 directly downregulated DNMT1 expression by targeting the 3'
      untranslated regions of its transcript. Interestingly, treatment of DNMT
      inhibitor, 5-aza-2-deoxycytidine, or depletion of DNMT1 led to increased miR-152
      expression by reversion of promoter hypermethylation, DNMT1 and MeCP2 binding to
      miR-152 promoter in NiS-transformed cells. Moreover, inhibition of miR-152
      expression in 16HBE cells could increase DNMT1 expression and result in an
      increase in DNA methylation, DNMT1 and MeCP2 binding to miR-152 promoter,
      indicating an interaction between miR-152 and DNMT1 is regulated by a double
      negative circuit. Furthermore, ectopic expression of miR-152 in NiS-transformed
      cells led to a significant decrease of cell growth. Conversely, inhibition of miR
      152 expression in 16HBE cells significantly increased cell growth. Taken
      together, these observations demonstrate a crucial functional crosstalk between
      miR-152 and the DNMT1 via a feedback loop involved in NiS-induced malignant
      transformation.

PMID- 23125219
TI  - Genotoxicity of alcohol is linked to DNA replication-associated damage and
      homologous recombination repair.
AB  - Although alcohol consumption is related to increased cancer risk, its molecular
      mechanism remains unclear. Here, we demonstrate that an intake of 10% alcohol for
      4 weeks in rats is genotoxic due to induction of micronuclei. Acetaldehyde (AA),
      the first product of ethanol metabolism, is believed to be responsible for DNA
      damage induced by alcohol. Here, we observe that AA effectively blocks DNA
      replication elongation in mammalian cells, resulting in DNA double-strand breaks
      associated with replication. AA-induced DNA damage sites colocalize with the
      homologous recombination (HR) repair protein RAD51. HR measured in the
      hypoxhantineguaninefosforibosyltransferase (HPRT) gene is effectively induced by
      AA and recombination defective mammalian cells are hypersensitive to AA, clearly
      demonstrating that HR is essential in the repair of AA-induced DNA damage.
      Altogether, our data indicate that alcohol genotoxicity related to AA produces
      replication lesions on DNA triggering HR repair.

PMID- 23125220
TI  - MicroRNA-144 promotes cell proliferation, migration and invasion in
      nasopharyngeal carcinoma through repression of PTEN.
AB  - Nasopharyngeal carcinoma (NPC) is a type of head and neck cancer with
      significantly high prevalence in Southern China. Unlike other head and neck
      cancers, mutations or deletions of tumor suppressor genes in NPC are not common.
      Recently, downregulation of tumor suppressor genes expression by microRNA (miRNA)
      is increasingly recognized as an important mechanism of nasopharyngeal
      tumorigenesis. In this study, we reported that microRNA-144 (miR-144) was
      frequently upregulated in NPC specimens and cell lines. Repression of miR-144
      significantly decreased cell proliferation, clonogenicity, migration, invasion
      and tumor formation in nude mice, while restoring miR-144 in miR-144-attenuated
      NPC cells exhibited a strong tumorigenic role. Further, we found that miR-144 was
      inversely correlated with the tumor suppressor gene phosphatase and tensin
      homolog (PTEN) in NPC specimens and cell lines, and then we identified PTEN as a
      direct target of miR-144 in NPC cell lines. PTEN downregulation in miR-144
      attenuated cells could increase cell growth, migration and invasion. Mechanistic
      investigations revealed that miR-144 suppressed the expression of PTEN to
      increase the expression of pAkt and cyclin D1 to promote G(1)-phase transition
      and decrease E-cadherin to promote migration and invasion. Taken together, we
      provide compelling evidence that miR-144 functions as an onco-miRNA in NPC, and
      its oncoeffects are mediated chiefly by repressing PTEN expression to activate
      the PI3K/Akt pathway.

PMID- 23125221
TI  - Ginsenoside Rh2 induces cell cycle arrest and differentiation in human leukemia
      cells by upregulating TGF-beta expression.
AB  - The triterpene saponin ginsenoside Rh2 has been shown to have antiproliferative
      effects on various cancer cells. However, the effect of Rh2 on the cell cycle and
      its underlying molecular mechanism in human leukemia cells are not fully
      understood. In this study, we found that Rh2 inhibited the proliferation of human
      leukemia cells concentration- and time-dependently with an IC(50) of ~38 uM. DNA
      flow cytometric analysis indicated that Rh2 blocked cell cycle progression at the
      G(1) phase in HL-60 and U937 cells, and this was found to be accompanied by the
      downregulations of cyclin-dependent kinase (CDK) 4, CDK6, cyclin D1, cyclin D2,
      cyclin D3 and cyclin E at the protein level. However, CDK inhibitors (CDKIs),
      such as p21(CIP1/WAF1) and p27(KIP1), were gradually upregulated after Rh2
      treatment at the protein and messenger RNA (mRNA) levels. In addition, Rh2
      markedly enhanced the bindings of p21(CIP1/WAF1) and p27(KIP1) to CDK2, CDK4 and
      CDK6, and these bindings reduced CDK2, CDK4 and CDK6 activities. Furthermore, Rh2
      induced the differentiation of HL-60 cells as demonstrated by biochemical assays
      and the expression levels of cell surface antigens. In addition, treatment of HL
      60 cells with Rh2 significantly increased transforming growth factor-beta (TGF
      beta) production, and cotreatment with TGF-beta neutralizing antibody prevented
      the Rh2-induced downregulations of CDK4 and CDK6, upregulations of p21(CIP1/WAF1)
      and p27(KIP1) levels and the induction of differentiation. These results
      demonstrate that the Rh2-mediated G(1) arrest and the differentiation are closely
      linked to the regulation of TGF-beta production in human leukemia cells.

PMID- 23125222
TI  - Curcumin-induced mitotic arrest is characterized by spindle abnormalities,
      defects in chromosomal congression and DNA damage.
AB  - The chemopreventive agent curcumin has anti-proliferative effects in many tumour
      types, but characterization of cell cycle arrest, particularly with
      physiologically relevant concentrations, is still incomplete. Following oral
      ingestion, the highest concentrations of curcumin are achievable in the gut.
      Although it has been established that curcumin induces arrest at the G(2)/M stage
      of the cell cycle in colorectal cancer lines, it is not clear whether arrest
      occurs at the G(2)/M transition or in mitosis. To elucidate the precise stage of
      arrest, we performed a direct comparison of the levels of curcumin-induced G(2)/M
      boundary and mitotic arrest in eight colorectal cancer lines (Caco-2, DLD-1, HCA
      7, HCT116p53+/+, HCT116p53(-)/(-), HCT116p21(-)/(-), HT-29 and SW480). Flow
      cytometry confirmed that these lines underwent G(2)/M arrest following treatment
      for 12h with clinically relevant concentrations of curcumin (5-10 MUM). In all
      eight lines, the majority of this arrest occurred at the G(2)/M transition, with
      a proportion of cells arresting in mitosis. Examination of the mitotic index
      using fluorescence microscopy showed that the HCT116 and Caco-2 lines exhibited
      the highest levels of curcumin-induced mitotic arrest. Image analysis revealed
      impaired mitotic progression in all lines, exemplified by mitotic spindle
      abnormalities and defects in chromosomal congression. Pre-treatment with
      inhibitors of the DNA damage signalling pathway abrogated curcumin-induced
      mitotic arrest, but had little effect at the G(2)/M boundary. Moreover, pH2A.X
      staining seen in mitotic, but not interphase, cells suggests that this aberrant
      mitosis results in DNA damage.

PMID- 23125223
TI  - Organomagnesium suppresses inflammation-associated colon carcinogenesis in male
      Crj: CD-1 mice.
AB  - Magnesium (Mg) deficiency increases genomic instability and Mg intake has been
      reported to be inversely associated with a risk of colorectal cancer (CRC). This
      study was designed to determine whether organo-Mg in drinking water suppresses
      inflammation-associated colon carcinogenesis in mice. Male Crj: CD-1 mice were
      initiated with a single i.p. injection of azoxymethane (AOM, 10mg/kg body weight)
      and followed by a 1 week exposure to dextran sulfate sodium (DSS, 1.5%, w/v) in
      drinking water to induce colonic neoplasms. They were then given the drinking
      water containing 7, 35 or 175 p.p.m. organo-Mg for 13 weeks. The chemopreventive
      efficacy of organo-Mg was determined 16 weeks after the AOM exposure.
      Administration with organo-Mg at all doses caused a significant inhibition of CRC
      development (P < 0.01 and P < 0.001). Especially, the highest dose of organo-Mg
      significantly suppressed the occurrence of all the colonic pathological lesions
      (mucosal ulcer, dysplasia, adenoma and adenocarcinoma). Organo-Mg also
      significantly reduced the number of mitoses/anaphase bridging, as well as
      proliferation of CRC. Additionally, at week 4, organo-Mg lowered the messenger
      RNA expression of certain proinflammatory cytokines, such as interleukin-1beta,
      interleukin-6, interferon-gamma and inducible nitric oxide synthase in the lesion
      free colorectal mucosa at week 4 but increased the Nrf-2 messenger RNA
      expression. Our findings that organo-Mg inhibits inflammation-related mouse colon
      carcinogenesis by modulating the proliferative activities and chromosomal
      instability of CRC and suppressing colonic inflammation may suggest potential use
      of organo-Mg for clinical chemoprevention trials of CRC in the inflamed colon.

PMID- 23125226
TI  - Oncrasin targets the JNK-NF-kappaB axis to sensitize glioma cells to TNFalpha
      induced apoptosis.
AB  - Resistance of glioblastoma multiforme (GBM) to tumor necrosis factor (TNF) alpha
      induced apoptosis have been attributed to increased nuclear factor-kappaB (NF
      kappaB) activation. As we have previously reported that certain anticancer
      chemotherapeutics can sensitize glioma cells to TNFalpha-induced apoptosis by
      abrogating NF-kappaB activation, we investigated the potential of oncrasin in
      sensitizing glioma cells to TNFalpha-induced apoptosis. Oncrasin reduced glioma
      cell viability, inhibited TNFalpha-mediated NF-kappaB activation and sensitized
      cells to TNFalpha-induced apoptosis. Apoptosis was accompanied by elevated Fas
      and Fas-associated death domain (FADD) levels, increased caspase-8 activation and
      formation of death-inducing signaling complex (DISC). Oncrasin also (i) affected
      expression of cell cycle regulators, (ii) triggered DNA damage response, (iii)
      induced G(2)/M cell cycle arrest, (iv) decreased telomerase activity, (v)
      abrogated STAT3 activation and (v) mediated extracellular release of high
      mobility group box 1 (HMGB1) along with its increased association with
      nucleosomes. Oncrasin-induced apoptosis did not involve mitochondria.
      Importantly, oncrasin increased c-jun N-terminal kinase (JNK) phosphorylation and
      pharmacological inhibition of JNK rescued oncrasin-induced apoptosis. JNK
      inhibition prevented oncrasin-induced decrease in TNFalpha-induced NF-kappaB
      activity and inhibition of NF-kappaB increased JNK phosphorylation in TNFalpha
      treated cells. Oncrasin induced DISC formation and inhibited anchorage
      independent growth of glioma cells in a JNK-dependent manner. By elucidating the
      existence of JNK-NF-kappaB cross-talk that regulates resistance to TNFalpha
      induced apoptosis, this study has highlighted the importance of JNK in regulating
      viability of glioma cells.

PMID- 23125225
TI  - Effects of limiting energy availability via diet and physical activity on
      mammalian target of rapamycin-related signaling in rat mammary carcinomas.
AB  - This study evaluated how different approaches to limiting energy availability
      (LEA) by 15% affected mammalian target of rapamycin (mTOR)-related signaling in
      mammary carcinomas. Female Sprague Dawley rats, injected with 50mg 1-methyl-1
      nitrosourea per kilogram body weight, were randomized to a control or three LEA
      interventions: (i) sedentary and restricted rats fed to 85% of energy available
      to the control or motorized wheel running (37 m/min) for an average of (ii) 1621
      +/- 55 (WRL) or (iii) 3094 +/- 126 (WRH) meters/day with food intake adjusted to
      provide the same net amount of available energy across LEA interventions. Under
      these conditions, LEA reduced overall cancer burden by 28% (P = 0.04) and down
      regulated mTOR-related signaling (Hotelling multivariate, P = 0.002). Among the
      regulatory nodes assessed, reduced levels of activated protein kinase B (pAkt)
      and induction of sirtuin 1 (SIRT1) were the most influential factors in
      distinguishing between sham control and LEA carcinomas. P-Akt was predictive of
      observed changes in levels of proteins involved in cell cycle control (r = 0.698,
      P < 0.0001) and induction of apoptosis (r = -0.429, P = 0.014). Plasma insulin
      and leptin were strongly associated with carcinoma pAkt levels. Consistent with
      downregulation of mTOR-related signaling by LEA, evidence of decreased lipid
      synthesis in carcinomas was observed (Hotelling multivariate, P < 0.001) and was
      negatively correlated with SIRT1 induction. Despite large differences between
      control and LEA, effects on mTOR regulation were insufficient to distinguish
      among LEA intervention groups. Given the modest effects observed on the LKB1/AMP
      activated protein kinase regulatory node, NADH and NADPH rather than ATP may be
      more limiting for tumor growth when LEA is 15%.

PMID- 23125224
TI  - Cell cycle-related genes as modifiers of age of onset of colorectal cancer in
      Lynch syndrome: a large-scale study in non-Hispanic white patients.
AB  - Heterogeneity in age of onset of colorectal cancer in individuals with mutations
      in DNA mismatch repair genes (Lynch syndrome) suggests the influence of other
      lifestyle and genetic modifiers. We hypothesized that genes regulating the cell
      cycle influence the observed heterogeneity as cell cycle-related genes respond to
      DNA damage by arresting the cell cycle to provide time for repair and induce
      transcription of genes that facilitate repair. We examined the association of
      1456 single nucleotide polymorphisms (SNPs) in 128 cell cycle-related genes and
      31 DNA repair-related genes in 485 non-Hispanic white participants with Lynch
      syndrome to determine whether there are SNPs associated with age of onset of
      colorectal cancer. Genotyping was performed on an Illumina GoldenGate platform,
      and data were analyzed using Kaplan-Meier survival analysis, Cox regression
      analysis and classification and regression tree (CART) methods. Ten SNPs were
      independently significant in a multivariable Cox proportional hazards regression
      model after correcting for multiple comparisons (P < 5 * 10(-4)). Furthermore,
      risk modeling using CART analysis defined combinations of genotypes for these
      SNPs with which subjects could be classified into low-risk, moderate-risk and
      high-risk groups that had median ages of colorectal cancer onset of 63, 50 and 42
      years, respectively. The age-associated risk of colorectal cancer in the high
      risk group was more than four times the risk in the low-risk group (hazard ratio
      = 4.67, 95% CI = 3.16-6.92). The additional genetic markers identified may help
      in refining risk groups for more tailored screening and follow-up of non-Hispanic
      white patients with Lynch syndrome.

PMID- 23125227
TI  - Preventative topical diclofenac treatment differentially decreases tumor burden
      in male and female Skh-1 mice in a model of UVB-induced cutaneous squamous cell
      carcinoma.
AB  - Ultraviolet B (UVB) light is the major environmental carcinogen contributing to
      non-melanoma skin cancer (NMSC) development. There are over 3.5 million NMSC
      diagnoses in two million patients annually, with men having a 3-fold greater
      incidence of squamous cell carcinoma (SCC) compared with women. Chronic
      inflammation has been linked to tumorigenesis, with a key role for the
      cyclooxygenase-2 (COX-2) enzyme. Diclofenac, a COX-2 inhibitor and non-steroidal
      anti-inflammatory drug, currently is prescribed to patients as a short-term
      therapeutic agent to induce SCC precursor lesion regression. However, its
      efficacy as a preventative agent in patients without evidence of precursor
      lesions but with significant UVB-induced cutaneous damage has not been explored.
      We previously demonstrated in a murine model of UVB-induced skin carcinogenesis
      that when exposed to equivalent UVB doses, male mice had lower levels of
      inflammation but developed increased tumor multiplicity, burden and grade
      compared with female mice. Because of the discrepancy in the degree of
      inflammation between male and female skin, we sought to determine if topical
      treatment of previously damaged skin with an anti-inflammatory COX-2 inhibitor
      would decrease tumor burden and if it would be equally effective in the sexes.
      Our results demonstrated that despite observed sex differences in the
      inflammatory response, prolonged topical diclofenac treatment of chronically UVB
      damaged skin effectively reduced tumor multiplicity in both sexes. Unexpectedly,
      tumor burden was significantly decreased only in male mice. Our data suggest a
      new therapeutic use for currently available topical diclofenac as a preventative
      intervention for patients predisposed to cutaneous SCC development before lesions
      appear.

PMID- 23125228
TI  - LINE-1-derived poly(A) microsatellites undergo rapid shortening and create
      somatic and germline mosaicism in mice.
AB  - Interspersed and tandem repeat sequences comprise the bulk of mammalian genomes.
      Interspersed repeats result from successive replication by transposable elements,
      such as Alu and long interspersed element type 1 (L1). Microsatellites are tandem
      repeats of 1-6 base pairs, among which poly(A) microsatellites are the most
      abundant in the human genome. The rise and fall of a microsatellite has been
      depicted as a life cycle. Previous studies have demonstrated that Alu and L1
      insertions are a major source of A-rich microsatellites owing to the concurrent
      formation of a poly(A) DNA tract at the 3'-end of each insertion. The fate of
      such poly(A) tracts has been studied by surveying the length distribution of
      genomic resident Alu and L1 insertions. However, these cross-sectional studies
      provide no information about the tempo of mutation immediately after birth. In
      this study, de novo L1 insertions were created using a transgenic L1 mouse model
      and traced through generations to investigate the early life of poly(A)
      microsatellites. High frequencies of intra-individual and intergenerational
      shortening were observed for long poly(A) tracts, creating somatic and germline
      mosaicism at the insertion site, whereas little variation was observed for short
      poly(A) alleles. As poly(A) microsatellites are the major intrinsic signal for
      nucleosome positioning, their remarkable abundance and variability make them a
      significant source of epigenetic variation. Thus, the birth of poly(A)
      microsatellites from retrotransposons and the subsequent rapid and variable
      shortening represent a new way with which retrotransposons can modify the genetic
      and epigenetic architecture of our genome.

PMID- 23125229
TI  - Yeast adapts to a changing stressful environment by evolving cross-protection and
      anticipatory gene regulation.
AB  - Organisms can protect themselves against future environmental change. An example
      is cross-protection, where physiological adaptation against a present
      environmental stressor can protect an organism against a future stressor. Another
      is anticipation, where an organism uses information about its present environment
      to trigger gene expression and other physiological changes adaptive in future
      environments. "Predictive" abilities like this exist in organisms that have been
      exposed to periodic changes in environments. It is unknown how readily they can
      evolve. To answer this question, we carried out laboratory evolution experiments
      in the yeast Saccharomyces cerevisiae. Specifically, we exposed three replicate
      populations of yeast to environments that varied cyclically between two
      stressors, salt stress and oxidative stress, every 10 generations, for a total of
      300 generations. We evolved six replicate control populations in only one of
      these stressors for the same amount of time. We analyzed fitness changes and
      genome-scale expression changes in all these evolved populations. Our populations
      evolved asymmetric cross protection, where oxidative stress protects against salt
      stress but not vice versa. Gene expression data also suggest the evolution of
      anticipation and basal gene expression changes that occur uniquely in cyclic
      environments. Our study shows that highly complex physiological states that are
      adaptive in future environments can evolve on very short evolutionary time
      scales.

PMID- 23125230
TI  - Endothelial NF-kappaB: the remote controller of the backyard fire in the vascular
      wall?

PMID- 23125231
TI  - Statin-induced lowering of LDL cholesterol associated with a reduced risk for
      cardiovascular events, not likely outweighed by the risk of diabetes, for people
      at low short-term risk of cardiovascular disease.

PMID- 23125232
TI  - Cranberry-containing products are associated with a protective effect against
      urinary tract infections.

PMID- 23125233
TI  - Statins induce hyperglycaemia of uncertain importance.

PMID- 23125234
TI  - Breastfeeding is protective against early childhood asthma.

PMID- 23125235
TI  - Double-balloon catheter results in higher rate of vaginal delivery within 24 h
      when compared with dinoprostone vaginal insert.

PMID- 23125236
TI  - Early surgery in infective endocarditis with large vegetations significantly
      reduced mortality compared with conventional treatment.

PMID- 23125237
TI  - Lactobacillus probiotics may prevent recurrent UTIs in postmenopausal women.

PMID- 23125238
TI  - Postpartum bleeding is reduced with sublingual powdered misoprostol when compared
      with oxytocin injection, but a new formulation of misoprostol is unlikely to
      revolutionise postpartum haemorrhage care.

PMID- 23125239
TI  - A brief intervention by emergency department providers decreased 12 month alcohol
      use.

PMID- 23125240
TI  - Early planned birth may reduce neonatal sepsis compared to expectant management
      following preterm premature rupture of the membranes close to term.

PMID- 23125241
TI  - Do educated natural killer cells make the grade in treating acute myeloid
      leukemia?

PMID- 23125242
TI  - Extramedullary involvement in multiple myeloma.

PMID- 23125243
TI  - A novel combination therapy approach for the treatment of acute myeloid leukemia:
      the multi-kinase inhibitor sorafenib and the HDM2 inhibitor nutlin-3.

PMID- 23125244
TI  - The use of age-dependent D-dimer cut-off values to exclude deep vein thrombosis.
      Reply to "Using an age-dependent D-dimer cut-off value increases the number of
      older patients in whom deep vein thrombosis can be safely excluded".
      Haematologica 2012;97(10):1507-13.

PMID- 23125245
TI  - Fc gamma receptor 3a genotype in follicular lymphoma: the end of the story? Reply
      to "Fc gamma receptor 3a genotype predicts overall survival in follicular
      lymphoma patients treated on SWOG trials with combined monoclonal antibody plus
      chemotherapy but not chemotherapy alone". Haematologica. 2012;97(6):937-942.

PMID- 23125247
TI  - The authors' reply--surgery for rheumatic mitral valve disease and the forgotten
      role of concomitant organic tricuspid valve impairment.

PMID- 23125248
TI  - Improvement of hyponatraemia during hospitalisation for acute heart failure is
      not associated with improvement of prognosis: an analysis from the Korean Heart
      Failure (KorHF) registry.
AB  - OBJECTIVE: Hyponatraemia predicts poor prognosis in patients hospitalised for
      acute heart failure (AHF). Yet, the association of hyponatraemia improvement with
      better postdischarge outcome has not been elucidated. Here, we determined the
      clinical impact of hyponatraemia improvement during hospitalisation on
      postdischarge outcome in patients admitted for AHF. DESIGN: Prospective cohort
      study. SETTING: Nation-wide twenty-four academic hospitals in Korea (mean follow
      up of 1.7 years after discharge). PATIENTS: 2888 patients hospitalised for AHF.
      MAIN OUTCOME MEASURES: Primary endpoints were composite of death or
      rehospitalisation due to heart failure. RESULTS: Hyponatraemia was present in 575
      of total 2888 patients hospitalised for AHF at admission. Hyponatraemia was
      normalised in 274 patients (47.7%) at discharge. During mean follow-up of 1.7
      years total 735 rehospitalisations and 397 deaths were documented. Persistent
      hyponatraemia during hospitalisation was significantly associated with increased
      incidence of composite endpoint of death or rehospitalisation in multivariate
      analysis compared with normonatraemia at admission (HR 1.345, 95% CI 1.075 to
      1.683, p=0.010). However, improvement of hyponatraemia during hospitalisation was
      not significantly associated with lower incidence of composite endpoint of death
      or rehospitalisation in multivariate analysis (HR 1.084, 95% CI 0.709 to 1.659,
      p=0.709). Improved hyponatraemia was not associated with better prognosis in
      analysis with propensity score matching, either (HR 1.111, 95% CI 0.588 to 2.100,
      p=0.746). CONCLUSIONS: In patients hospitalised for AHF, hyponatraemia on
      admission is associated with a worse prognosis compared with normonatraemia,
      irrespective of whether hyponatraemia improves during hospitalisation.

PMID- 23125249
TI  - Discrepancy between mitral valve areas measured by two-dimensional planimetry and
      three-dimensional transoesophageal echocardiography in patients with mitral
      stenosis.
AB  - OBJECTIVE: To compare mitral valve area (MVA) measurements obtained by 2D
      transthoracic planimetry and 3D transoesophageal echocardiography (TOE) in
      patients with mitral stenosis (MS), and to determine the causes of discrepancies
      between the two techniques. DESIGN: Reliability and agreement study. SETTING:
      Tertiary referral centre. PATIENTS: Eighty-seven patients with MS. METHODS: MVA
      was determined by transthoracic 2D planimetry and 3D TOE. Clinical and
      echocardiographic variables were evaluated. The angle (Malpha) between the lines
      of the true mitral valve (MV) tip and the echo beam-to-MV tip was measured at
      early diastole from the parasternal long-axis view obtained from 2D
      echocardiography. RESULTS: Although MVA measurements using 2D planimetry and 3D
      TOE showed good agreement (intraclass correlation coefficient, 0.853; p<0.001),
      2D planimetry overestimated MVA by 0.19+/-0.2 cm(2) compared with 3D TOE
      (p<0.001). Left atrial (LA) dimension obtained from the parasternal long-axis
      view at end-systole (p=0.012), Malpha (p<0.001), and left ventricular ejection
      fraction (p=0.022) were independent determinants of the MVA difference (MVA by 2D
      MVA by 3D TOE; MVA(2D-3D)) according to multiple linear regression analysis. The
      LA dimensions correlated with Malpha (r=0.352, p=0.001). The best cut-off values
      for predicting significant overestimation by 2D planimetry (MVA(2D-3D)>0.2 cm(2))
      were LA dimension >=49 mm (78% sensitivity, 72% specificity) and Malpha>=9.5
      degrees  (56% sensitivity, 89% specificity). CONCLUSIONS: Because 2D planimetry
      tends to overestimate MVA, 3D TOE should be considered for accurate MVA
      assessment, especially in patients with a large LA and large Malpha.

PMID- 23125250
TI  - Defining the best time point to maximise the prognostic value of biomarkers.

PMID- 23125251
TI  - Development and characterization of a 3D multicell microtissue culture model of
      airway smooth muscle.
AB  - Airway smooth muscle (ASM) cellular and molecular biology is typically studied
      with single-cell cultures grown on flat 2D substrates. However, cells in vivo
      exist as part of complex 3D structures, and it is well established in other cell
      types that altering substrate geometry exerts potent effects on phenotype and
      function. These factors may be especially relevant to asthma, a disease
      characterized by structural remodeling of the airway wall, and highlights a need
      for more physiologically relevant models of ASM function. We utilized a tissue
      engineering platform known as microfabricated tissue gauges to develop a 3D
      culture model of ASM featuring arrays of ~0.4 mm long, ~350 cell "microtissues"
      capable of simultaneous contractile force measurement and cell-level microscopy.
      ASM-only microtissues generated baseline tension, exhibited strong cellular
      organization, and developed actin stress fibers, but lost structural integrity
      and dissociated from the cantilevers within 3 days. Addition of 3T3-fibroblasts
      dramatically improved survival times without affecting tension development or
      morphology. ASM-3T3 microtissues contracted similarly to ex vivo ASM, exhibiting
      reproducible responses to a range of contractile and relaxant agents. Compared
      with 2D cultures, microtissues demonstrated identical responses to acetylcholine
      and KCl, but not histamine, forskolin, or cytochalasin D, suggesting that
      contractility is regulated by substrate geometry. Microtissues represent a novel
      model for studying ASM, incorporating a physiological 3D structure, realistic
      mechanical environment, coculture of multiple cells types, and comparable
      contractile properties to existing models. This new model allows for rapid
      screening of biochemical and mechanical factors to provide insight into ASM
      dysfunction in asthma.

PMID- 23125252
TI  - IL-13 receptor alpha2-arginase 2 pathway mediates IL-13-induced pulmonary
      hypertension.
AB  - Although previous literature suggests that interleukin (IL)-13, a T-helper type 2
      cell effector cytokine, might be involved in the pathogenesis of pulmonary
      hypertension (PH), direct proof is lacking. Furthermore, a potential mechanism
      underlying IL-13-induced PH has never been explored. This study's goal was to
      investigate the role and mechanism of IL-13 in the pathogenesis of PH. Lung
      specific IL-13-overexpressing transgenic (Tg) mice were examined for hemodynamic
      changes and pulmonary vascular remodeling. IL-13 Tg mice spontaneously developed
      PH phenotype by the age of 2 mo with increased expression and activity of
      arginase 2 (Arg2). The role of Arg2 in the development of IL-13-stimulated PH was
      further investigated using Arg2 and IL-13 receptor alpha2 (Ralpha2) null mutant
      mice and the small-interfering RNA (siRNA)-silencing approach in vivo and in
      vitro, respectively. IL-13-stimulated medial thickening of pulmonary arteries and
      right ventricle systolic pressure were significantly decreased in the IL-13 Tg
      mice with Arg2 null mutation. On the other hand, the production of nitric oxide
      was further increased in the lungs of these mice. In our in vitro evaluations,
      the recombinant IL-13 treatment significantly enhanced the proliferation of human
      pulmonary artery smooth muscle cells in an Arg2-dependent manner. The IL-13
      stimulated cellular proliferation and the expression of Arg2 in hpaSMC were
      markedly decreased with IL-13Ralpha2 siRNA silencing. Our studies demonstrate
      that IL-13 contributes to the development of PH via an IL-13Ralpha2-Arg2
      dependent pathway. The intervention of this pathway could be a potential
      therapeutic target in pulmonary arterial hypertension.

PMID- 23125253
TI  - Enhancing community knowledge and health behaviors to eliminate blinding trachoma
      in Mali using radio messaging as a strategy.
AB  - The National Blindness Prevention Program in Mali has broadcast messages on the
      radio about trachoma as part of the country's trachoma elimination strategy since
      2008. In 2011, a radio impact survey using multi-stage cluster sampling was
      conducted in the regions of Kayes and Segou to assess radio listening habits,
      coverage of the broadcasts, community knowledge and behavior specific to trachoma
      and facial cleanliness of children. Radio access and listening were high, with
      60% of respondents having heard a message on the radio about trachoma. The
      majority of respondents knew about trachoma, its root causes, its impact on
      health and prevention measures. Additionally, 66% reported washing their
      children's faces more than or equal to twice/day and 94% reported latrine
      disposal of feces. A high percentage of persons who gave a positive response to
      knowledge and behavior questions reported hearing the trachoma messages on the
      radio with 60% reporting that the radio is where they learned about trachoma.
      There was no significant difference in facial cleanliness when comparing children
      whose primary caregiver had/had not heard the trachoma messages. Next steps
      include revising the current messages to include more focused behavior change
      messaging and to engage in a more robust use of community radios.

PMID- 23125254
TI  - MPs call on the Government to stop the badger cull.

PMID- 23125255
TI  - Vets tell MPs that dog welfare council should become a regulatory body.

PMID- 23125256
TI  - Concern about impact of new vet school.

PMID- 23125257
TI  - Research suggests 'hidden burden' of bovine TB infection.

PMID- 23125258
TI  - Top dogs at Westminster.

PMID- 23125259
TI  - Guide to stop feathers being ruffled.

PMID- 23125260
TI  - Adapting to life in a digital world.

PMID- 23125262
TI  - Vet removed from the Register following welfare offences.

PMID- 23125263
TI  - Aiding the transition from vet school to practice.

PMID- 23125264
TI  - Ethical decision-making in veterinary practice: using the head and the heart.

PMID- 23125265
TI  - Suspected ethanol toxicity in juvenile blackbirds and redwings.

PMID- 23125266
TI  - Canine trombiculosis and seasonal canine illness.

PMID- 23125267
TI  - Bovine TB and badger culling.

PMID- 23125268
TI  - Bovine TB and badger culling.

PMID- 23125275
TI  - Study of 23 advanced-practice nurses suggest that their ability to facilitate
      evidence-based practice among frontline nurses is influenced by their personal
      attributes, relationships with stakeholders, responsibility and workload and
      organisational context.
AB  - Implications for practice and research: Role development of advance practice
      nurses (APNs) and organisational culture are important contributing factors for
      the adoption of evidence-based practice (EBP) by nurses. Nursing and APN workload
      were factors limiting adoption of EBPs. Education on EBP, leadership and
      facilitation should be part of all APN education. Further research across a range
      of settings is needed to determine additional factors that may influence adoption
      of EBP.

PMID- 23125276
TI  - Among elderly men, feelings of loneliness are associated with increased 10-year
      mortality risk, independent of social isolation and medical and psychiatric
      conditions.
AB  - Implications for practice and research: Clinicians should have heightened
      awareness and inquire about feelings of loneliness when providing care for older
      adults. More studies are needed to further elucidate gender-based differences on
      the relationship between loneliness and mortality.

PMID- 23125277
TI  - Overweight and obese middle-aged women have increased risk of venous
      thromboembolism, particularly following surgery.
AB  - Implications for practice and research: Obesity is associated with an increased
      risk of venous thromboembolism (VTE) including both spontaneous and postoperative
      events. Further research is needed regarding factors responsible for the increase
      in postoperative VTE in overweight patients, and whether management should be
      altered (eg, increased focus on postoperative mobilisation,altered doses of
      prophylactic anticoagulants, lower threshold for starting prophylactic
      anticoagulation for minor surgical procedures). Weight loss prior to surgery may
      reduce risk of venous thrombosis.

PMID- 23125278
TI  - Management of pericardial effusion.
AB  - Pericardial effusion is a common finding in clinical practice either as
      incidental finding or manifestation of a systemic or cardiac disease. The
      spectrum of pericardial effusions ranges from mild asymptomatic effusions to
      cardiac tamponade. The aetiology is varied (infectious, neoplastic, autoimmune,
      metabolic, and drug-related), being tuberculosis the leading cause of pericardial
      effusions in developing countries and all over the world, while concurrent HIV
      infection may have an important promoting role in this setting. Management is
      guided by the haemodynamic impact, size, presence of inflammation (i.e.
      pericarditis), associated medical conditions, and the aetiology whenever
      possible. Pericardiocentesis is mandatory for cardiac tamponade and when a
      bacterial or neoplastic aetiology is suspected. Pericardial biopsy is generally
      reserved for cases with recurrent cardiac tamponade or persistence without a
      defined aetiology, especially when a bacterial or neoplastic aetiology is
      suspected and cannot be assessed by other conventional and less invasive means. A
      true isolated effusion may not require a specific treatment if the patient is
      asymptomatic, but large ones are at risk of progression to cardiac tamponade (up
      to one third). Pericardiocentesis alone may be curative for large effusions, but
      recurrences are also common and pericardiectomy or less invasive options (i.e.
      pericardial window) should be considered with recurrent cardiac tamponade or
      symptomatic pericardial effusion (either circumferential or loculated). The aim
      of this paper was to summarize and critically evaluate current knowledge on the
      management of pericardial effusion.

PMID- 23125279
TI  - The STarT back screening tool and individual psychological measures: evaluation
      of prognostic capabilities for low back pain clinical outcomes in outpatient
      physical therapy settings.
AB  - BACKGROUND: Psychologically informed practice emphasizes routine identification
      of modifiable psychological risk factors being highlighted. OBJECTIVE: The
      purpose of this study was to test the predictive validity of the STarT Back
      Screening Tool (SBT) in comparison with single-construct psychological measures
      for 6-month clinical outcomes. DESIGN: This was an observational, prospective
      cohort study. METHODS: Patients (n=146) receiving physical therapy for low back
      pain were administered the SBT and a battery of psychological measures (Fear
      Avoidance Beliefs Questionnaire physical activity scale and work scale [FABQ-PA
      and FABQ-W, respectively], Pain Catastrophizing Scale [PCS], 11-item version of
      the Tampa Scale of Kinesiophobia [TSK-11], and 9-item Patient Health
      Questionnaire [PHQ-9]) at initial evaluation and 4 weeks later. Treatment was at
      the physical therapist's discretion. Clinical outcomes consisted of pain
      intensity and self-reported disability. Prediction of 6-month clinical outcomes
      was assessed for intake SBT and psychological measure scores using multiple
      regression models while controlling for other prognostic variables. In addition,
      the predictive capabilities of intake to 4-week changes in SBT and psychological
      measure scores for 6-month clinical outcomes were assessed. RESULTS: Intake pain
      intensity scores (beta=.39 to .45) and disability scores (beta=.47 to .60) were
      the strongest predictors in all final regression models, explaining 22% and 24%
      and 43% and 48% of the variance for the respective clinical outcome at 6 months.
      Neither SBT nor psychological measure scores improved prediction of 6-month pain
      intensity. The SBT overall scores (beta=.22) and SBT psychosocial scores
      (beta=.25) added to the prediction of disability at 6 months. Four-week changes
      in TSK-11 scores (beta=-.18) were predictive of pain intensity at 6 months. Four
      week changes in FABQ-PA scores (beta=-.21), TSK-11 scores (beta=-.20) and SBT
      overall scores (beta=-.18) were predictive of disability at 6 months.
      LIMITATIONS: Physical therapy treatment was not standardized or accounted for in
      the analysis. CONCLUSIONS: Prediction of clinical outcomes by psychology-based
      measures was dependent upon the clinical outcome domain of interest. Similar to
      studies from the primary care setting, initial screening with the SBT provided
      additional prognostic information for 6-month disability and changes in SBT
      overall scores may provide important clinical decision-making information for
      treatment monitoring.

PMID- 23125280
TI  - Participants' perspectives on the feasibility of a novel, intensive, task
      specific intervention for individuals with chronic stroke: a qualitative
      analysis.
AB  - BACKGROUND: Evidence-based practice promotes patient-centered care, yet the
      majority of rehabilitative research fails to take patient perspectives into
      consideration. Qualitative research provides a unique opportunity for patients to
      express opinions and provide valuable insight on intervention processes.
      OBJECTIVE: The purpose of this study was to assess the feasibility of a novel,
      intensive, task-specific intervention from the patient's perspective. DESIGN: A
      phenomenological approach to qualitative inquiry was used. METHODS: Eight
      individuals with chronic stroke participated in an intensive intervention, 3
      hours per day for 10 consecutive days. Participants were interviewed twice
      regarding their impressions of the therapy, and a focus group was conducted with
      participants and family members. Data analysis included an analytical thematic
      approach. RESULTS: Five major themes arose related to the feasibility of the
      intervention: (1) a manageable amount of fatigue; (2) a difficult, yet doable,
      level of intensity; (3) a disappointingly short therapy duration; (4) enjoyment
      of the intervention; and (5) muscle soreness. CONCLUSIONS: The findings suggest
      that participants perceived this novel and intensive, task-specific intervention
      as a feasible therapeutic option for individuals with chronic stroke. Despite the
      fatigue and muscle soreness associated with intensive rehabilitation,
      participants frequently reported enjoying the therapy and stated disappointment
      with the short duration (10 days). Future research should include a feasibility
      trial of longer duration, as well as a qualitative analysis of the benefits
      associated with the intervention.

PMID- 23125281
TI  - Many randomized trials of physical therapy interventions are not adequately
      registered: a survey of 200 published trials.
AB  - BACKGROUND: Clinical trial registration has several putative benefits: prevention
      of selective reporting, avoidance of duplication, encouragement of participation,
      and facilitation of reviews. Previous surveys suggest that most trials are
      registered. However, these surveys examined only trials in journals with high
      impact factors, which may bias the results. PURPOSE: This study examined the
      completeness of clinical trial registration and the extent of selective reporting
      of outcomes in a random sample of published randomized trials in physical
      therapy. DATA SOURCES: This was a retrospective cohort study in which 200
      randomized trials of physical therapy interventions were randomly selected from
      those published in 2009 and indexed in the Physiotherapy Evidence Database
      (PEDro), regardless of the publishing journal. DATA EXTRACTION: Evidence of
      registration was sought for each trial in the study, on clinical trial registers,
      and by contacting authors. DATA SYNTHESIS: The proportion of randomized trials
      that were registered was 67/200 (34%). This proportion was significantly lower
      than among the trials in journals with high impact factors, where the proportion
      was 75% (odds ratio=7.4, 95% confidence interval=2.6-21.4). Unambiguous primary
      outcomes (ie, method and time points of measurement clearly defined in the trial
      registry entry) were registered for 32 trials, and registration was adequate (ie,
      prospective with unambiguous primary outcomes) for 5/200 (2.5%) trials. Selective
      outcome reporting occurred in 23 (47%) of the 49 trials in which selective
      reporting was assessable. LIMITATIONS: The inclusion of only English-language
      trials prevents generalization of the results to non-English-language trials.
      CONCLUSIONS: Registration of randomized trials of physical therapy interventions
      is rarely adequate. Consequently, the putative benefits of registration are not
      being fully realized.

PMID- 23125282
TI  - Trans-chromosomic mice containing a human CYP3A cluster for prediction of
      xenobiotic metabolism in humans.
AB  - Human CYP3A is the most abundant P450 isozyme present in the human liver and
      small intestine, and metabolizes around 50% of medical drugs on the market. The
      human CYP3A subfamily comprises four members (CYP3A4, CYP3A5, CYP3A7, CYP3A43)
      encoded on human chromosome 7. However, transgenic mouse lines carrying the
      entire human CYP3A cluster have not been constructed because of limitations in
      conventional cloning techniques. Here, we show that the introduction of a human
      artificial chromosome (HAC) containing the entire genomic human CYP3A locus
      recapitulates tissue- and stage-specific expression of human CYP3A genes and
      xenobiotic metabolism in mice. About 700 kb of the entire CYP3A genomic segment
      was cloned into a HAC (CYP3A-HAC), and trans-chromosomic (Tc) mice carrying a
      single copy of germline-transmittable CYP3A-HAC were generated via a chromosome
      engineering technique. The tissue- and stage-specific expression profiles of
      CYP3A genes were consistent with those seen in humans. We further generated mice
      carrying the CYP3A-HAC in the background homozygous for targeted deletion of most
      endogenous Cyp3a genes. In this mouse strain with 'fully humanized' CYP3A genes,
      the kinetics of triazolam metabolism, CYP3A-mediated mechanism-based inactivation
      effects and formation of fetal-specific metabolites of dehydroepiandrosterone
      observed in humans were well reproduced. Thus, these mice are likely to be
      valuable in evaluating novel drugs metabolized by CYP3A enzymes and in studying
      the regulation of human CYP3A gene expression. Furthermore, this system can also
      be used for generating Tc mice carrying other human metabolic genes.

PMID- 23125283
TI  - MicroRNA-205 regulates the expression of Parkinson's disease-related leucine-rich
      repeat kinase 2 protein.
AB  - Recent genome-wide association studies indicate that a simple alteration of
      Leucine-rich repeat kinase 2 (LRRK2) gene expression may contribute to the
      etiology of sporadic Parkinson's disease (PD). However, the expression and
      regulation of LRRK2 protein in the sporadic PD brains remain to be determined.
      Here, we found that the expression of LRRK2 protein was enhanced in the sporadic
      PD patients using the frontal cortex tissue from a set of 16 PD patients and 7
      control samples. In contrast, no significant difference was detected in the level
      of LRRK2 mRNA expression between the control and PD cases, suggesting a potential
      post-transcriptional modification of the LRRK2 protein expression in the sporadic
      PD brains. Indeed, it was identified that microRNA-205 (miR-205) suppressed the
      expression of LRRK2 protein through a conserved-binding site at the 3'
      untranslated region (UTR) of LRRK2 gene. Interestingly, miR-205 expression was
      significantly downregulated in the brains of patients with sporadic PD, showing
      the enhanced LRRK2 protein levels. Also, in vitro studies in the cell lines and
      primary neuron cultures further established the role of miR-205 in modulating the
      expression of LRRK2 protein. In addition, introduction of miR-205 prevented the
      neurite outgrowth defects in the neurons expressing a PD-related LRRK2 R1441G
      mutant. Together, these findings suggest that downregulation of miR-205 may
      contribute to the potential pathogenic elevation of LRRK2 protein in the brains
      of patients with sporadic PD, while overexpression of miR-205 may provide an
      applicable therapeutic strategy to suppress the abnormal upregulation of LRRK2
      protein in PD.

PMID- 23125284
TI  - A mutation in the FAM36A gene, the human ortholog of COX20, impairs cytochrome c
      oxidase assembly and is associated with ataxia and muscle hypotonia.
AB  - The mitochondrial respiratory chain complex IV (cytochrome c oxidase) is a multi
      subunit enzyme that transfers electrons from cytochrome c to molecular oxygen,
      yielding water. Its biogenesis requires concerted expression of mitochondria- and
      nuclear-encoded subunits and assembly factors. In this report, we describe a
      homozygous missense mutation in FAM36A from a patient who displays ataxia and
      muscle hypotonia. The FAM36A gene is a remote, putative ortholog of the fungal
      complex IV assembly factor COX20. Messenger RNA (mRNA) and protein co-expression
      analyses support the involvement of FAM36A in complex IV function in mammals. The
      c.154A>C mutation in the FAM36A gene, a mutation that is absent in sequenced
      exomes, leads to a reduced activity and lower levels of complex IV and its
      protein subunits. The FAM36A protein is nearly absent in patient's fibroblasts.
      Cells affected by the mutation accumulate subassemblies of complex IV that
      contain COX1 but are almost devoid of COX2 protein. We observe co-purification of
      FAM36A and COX2 proteins, supporting that the FAM36A defect hampers the early
      step of complex IV assembly at the incorporation of the COX2 subunit. Lentiviral
      complementation of patient's fibroblasts with wild-type FAM36A increases the
      complex IV activity as well as the amount of holocomplex IV and of individual
      subunits. These results establish the function of the human gene FAM36A/COX20 in
      complex IV assembly and support a causal role of the gene in complex IV
      deficiency.

PMID- 23125285
TI  - Is retrograde cerebral perfusion dead?

PMID- 23125286
TI  - Reply to Myers et al.

PMID- 23125287
TI  - Biodegradable materials for tricuspid valve repair in infective endocarditis.

PMID- 23125288
TI  - Ductal pseudoaneurysm as a late complication of patent ductus arteriosus
      ligation.

PMID- 23125289
TI  - Plasma Dickkopf1 (DKK1) concentrations negatively associate with atherosclerotic
      calcified plaque in African-Americans with type 2 diabetes.
AB  - BACKGROUND: Bone mineral density (BMD) and atherosclerotic arterial calcified
      plaque (CP) demonstrate inverse relationships through unknown mechanisms.
      Dickkopf-1 (DKK1) is an endogenous inhibitor of bone formation, and serum DKK1
      has been associated with impaired osteoblast activation and susceptibility to
      bone loss. Plasma DKK1, BMD in the spine, and CP in three arterial beds were
      assessed in African-Americans (AAs) to determine relationships of serum DKK1 with
      atherosclerotic vascular calcification. METHODS: Plasma DKK1, computed tomography
      derived trabecular volumetric BMD (vBMD) in thoracic and lumbar vertebrae, and
      coronary artery, carotid artery, and aortoiliac CP were measured in 450 unrelated
      AAs with type 2 diabetes. Generalized linear models were fitted to test for
      associations between DKK1, vBMD, and CP. RESULTS: Participants were 56% female
      with mean/SD/median age of 55.4/9.5/55.0 yr, diabetes duration of 10.3/8.2/8.0
      yr, plasma DKK1 of 481.6/271.8/417 pg/ml, coronary artery CP mass score of
      284/648/13, carotid artery CP mass score of 46/132/0, and aortoiliac CP mass
      score of 1613/2910/282. Adjusting for age, sex, body mass index, mean arterial
      blood pressure, smoking, hemoglobin A(1c), and low-density lipoprotein
      cholesterol, DKK1 was inversely associated with coronary artery and aortoiliac CP
      [parameter estimates -0.0011 (P = 0.0137) and -0.0010 (P = 0.0214),
      respectively], with a trend for carotid artery CP (P = 0.1404). No associations
      were observed between DKK1 and vBMD in the thoracic or lumbar vertebrae.
      CONCLUSIONS: Plasma DKK1 levels were inversely associated with coronary artery
      and aortoiliac CP, but not vBMD, in this cross-sectional study of AAs with type 2
      diabetes. DKK1 may play a role in vascular mineral metabolism in this clinical
      setting.

PMID- 23125290
TI  - Bone mineral density and body composition in short children born SGA during
      growth hormone and gonadotropin releasing hormone analog treatment.
AB  - CONTEXT: Postponement of puberty by GnRH analog (GnRHa) in addition to GH
      treatment might increase adult height (AH) in short adolescents born small for
      gestational age (SGA). GnRHa treatment is thought to have negative effects on
      bone mineral density (BMD) and body composition. OBJECTIVE: The objective of the
      study was to assess the BMD of total body (BMD(TB)), lumbar spine (BMD(LS)), bone
      mineral apparent density lumbar spine (BMAD(LS)), lean body mass, fat mass, and
      fat distribution during GH treatment, with or without an additional 2 yr of
      GnRHa. PATIENTS AND DESIGN: This was a prospective GH trial involving short SGA
      adolescents (>=8 yr). Eighty-eight children (50 girls) were treated until AH (GH
      randomized 1 or 2 mg/m(2) . d during puberty); 52 of these children received
      additional GnRHa. BMD and body composition were longitudinally assessed by dual
      energy X-ray absorptiometry. RESULTS: Baseline BMD(TB) sd score (SDS) and BMD(LS)
      SDS were significantly reduced (both P < 0.001), but BMAD(LS) SDS was comparable
      with zero (P = 0.129). BMD(TB) SDS and BMD(LS) SDS improved (both P < 0.001) from
      the start until AH, whereas BMAD(LS) SDS remained similar (P = 0.168). At AH, 93%
      of patients had a normal BMD(TB), 99% a normal BMD(LS), and 98% a normal BMAD(LS)
      (> -2 and < +2 SDS). From the start until AH, lean body mass SDS(height) and fat
      mass SDS increased significantly toward zero (both P <0.001). Multiple regression
      analyses showed that additional GnRHa treatment had no adverse effect on the
      changes in BMD and body composition during GH treatment, also after correction
      for influencing variables. CONCLUSION: Untreated short SGA adolescents had
      reduced BMD(TB) and BMD(LS) but normal bone size-corrected BMAD(LS). During GH
      treatment, BMD(TB) and BMD(LS) increased significantly, leading to a normal adult
      BMD in almost all patients. Two years of GnRHa in addition to GH treatment had no
      adverse effect on BMD or body composition.

PMID- 23125291
TI  - Chronic asymptomatic dislocation of the bearing in an Oxford unicompartmental
      knee replacement.
AB  - Unicompartmental knee replacement is a common procedure for the treatment of
      osteoarthritis confined to one compartment of the knee. Dislocation of the mobile
      bearing is a recognised complication. We present a patient with a 6-year
      asymptomatic bearing dislocation, missed on original presentation.

PMID- 23125292
TI  - The importance of cardiac MR in diagnosis of myocarditis in a 30-year-old man
      presenting with inferior ST elevation, elevated cardiac troponin but unobstructed
      coronary arteries.
AB  - A 30-year-old man presented with chest pain, inferior ST elevation and elevated
      troponin T. Emergency coronary angiography showed unobstructed coronary arteries.
      A clinical diagnosis of myocarditis was made. This was supported by cardiac MRI
      (CMR) which showed a dilated left ventricle with severely impaired systolic
      function, and patchy delayed gadolinium enhancement (DGE). He was admitted to the
      coronary care unit where he had episodes of monomorphic ventricular tachycardia
      (VT). He was treated with ACE inhibitors, beta-blockers and corticosteroids.
      Targeted cardiac biopsies were taken during admission, and also 6 weeks later;
      none showed histological evidence of myocarditis. Repeat CMR on day 11 showed
      improvement in left ventricular systolic function, extent of oedema and DGE. He
      has subsequently had episodes of nonsustained ventricular tachycardia and
      evidence of established myocardial scar on CMR several months later.

PMID- 23125293
TI  - Viral encephalitis and atherothrombotic stroke.
AB  - The clinical hallmark of viral encephalitis is an acute febrile illness, but
      stroke-like presentations have been rarely described. We report a patient who
      arrived at A&E with an acute right middle cerebral artery syndrome, without
      fever. Following thrombolytic treatment, clinical deficit almost disappeared and
      a critical ipsilateral carotid stenosis was identified. Stenting was implemented
      and 7 days later the patient started with high fever and reappearance of the
      initial deficit. Hyperperfusion syndrome and pneumonia were initially considered
      as the diagnosis but herpetic encephalitis (HE) was the final diagnosis. A very
      good response to antiviral treatment was achieved. We discuss whether the patient
      suffered from an unusual sudden stroke-like onset HE without encephalitic
      features or whether a stroke led to delayed HE.

PMID- 23125294
TI  - Digital gangrene as the initial presentation of systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) has rarely been reported among African blacks.
      However, recent reports may indicate otherwise. Digital gangrene in lupus
      patients has been reported in different populations and has mostly been seen in
      patients with long-standing lupus. Digital gangrene as the initial presentation
      of SLE has rarely been reported, even among African blacks. Two cases of digital
      gangrene as the initial presentation in Nigerian lupus patients are hereby
      presented. The medical and surgical managements, as well as relevant literature
      are hereby discussed.

PMID- 23125295
TI  - Atypical 'benign behaviour' of eyelid sebaceous carcinoma.
AB  - Eyelid sebaceous carcinoma is a rare tumour with slow growth and it is one of the
      most aggressive malignancies of the eyelid. Death rate can reach 6%. The
      diagnosis is often delayed because it is confused with other periocular lesions.
      The authors describe a case with atypical presentation, regarding rapid growth
      rate and exophytic aspect. Female, 78 years, presenting lower eyelid tumour with
      4 months of evolution. Ophthalmological examination showed a tarsal exophytic
      tumour (22 mm), non-adherent to bulbar conjunctiva. She was medicated topically
      for 3 months, with the diagnosis of chalazio. Total excision was performed for
      histological diagnosis. After diagnosis of sebaceous carcinoma with specific
      immunohistochemical markers, and without free tumour surgical limits, a second
      surgery was performed with a pentagon entire thickness excision. Being a rare
      tumour but with a considerable morbidity and mortality; early diagnosis and
      treatment is essential for a good prognosis and preservation of visual function.

PMID- 23125296
TI  - A staged management of prolonged chylothorax in a patient with yellow nail
      syndrome.
AB  - Spontaneous chylothorax remains an unusual condition with diverse aetiologies and
      non-unified management strategies. Owing to the rarity of the condition, the
      evidence of management remains from case reports and limited retrospective
      studies. This case represents a difficult-to-manage chylothorax secondary to
      yellow nail syndrome with initial failure of both surgical and conservative
      treatment methods. Pleurovenous shunting represents a surgical management
      approach allowing the patient to live with and control an ongoing chyle leak.

PMID- 23125297
TI  - Clinical benefits of alpharadin in castrate-chemotherapy-resistant prostate
      cancer: case report and literature review.
AB  - Prostate cancer has the second-highest mortality worldwide in men. The most
      common site of metastasis is bone. Bone metastases and their resulting
      complications represent a significant source of morbidity. Radioisotopes have
      been used for treatment of painful bony metastases. Although shown to decrease
      pain and analgesia use, this has not improved outcomes. The following case report
      describes a patient with castrate-resistant prostate cancer who was treated with
      the radioisotope radium-223 as part of the phase III clinical trial Alpharadin in
      Patients with Symptomatic Hormone Refractory Prostate Cancer with Skeletal
      Metastases (ALSYMPCA). He responded to radium-223 with pain relief, bone scan
      response, stabilisation of prostate specific antigen (PSA) and normalisation of
      alkaline phosphatase. Interim analysis of this trial has shown that radium-223
      significantly prolongs overall survival, time to first skeletal-related event and
      is well tolerated. Alpharadin is a new treatment option for men with castrate
      resistant prostate cancer and symptomatic bone metastases.

PMID- 23125298
TI  - Silent sinus syndrome.

PMID- 23125299
TI  - Pregnancy in Shwachman-Diamond syndrome: a novel genetic mutation with minimal
      consequence.
AB  - Shwachman-Diamond syndrome (SDS) is a rare inherited bone marrow failure
      syndrome, characterised by neutropenia, exocrine pancreatic dysfunction and often
      skeletal abnormalities. To date, and to our knowledge, we report a novel genetic
      mutation in SDS that, we believe, is associated with minimal consequence,and
      report the fertility and pregnancy in this individual.

PMID- 23125300
TI  - Fetal warfarin syndrome.
AB  - A case of a baby born preterm with an antenatal diagnosis of aortic coarctation
      for which prostin was electively started at birth. The baby was found to be
      profoundly anaemic with no clear obstetric cause. Features consistent with
      antenatal intracerebral haemorrhage were noted on cranial ultrasonography in the
      context of severe coagulopathy, prompting investigations which confirmed fetal
      maternal haemorrhage. It transpired that, following aortic and mitral valve
      replacements, the mother was anticoagulated with warfarin at conception, having
      misunderstood her cardiologist's advice that: 'you cannot get pregnant whilst on
      warfarin'. Following conversion to low molecular weight heparin, she suffered a
      stroke, thus warfarin was restarted, with an international normalised ratio of 3
      4.7 during pregnancy. Following transfer to the paediatric intensive care unit,
      fetal warfarin syndrome was diagnosed. The coagulopathy and anaemia were
      corrected and aortic coarctation was excluded. The baby returned to the neonatal
      intensive care unit for ongoing care and was discharged home in good condition
      around his due date. At the present time, there is no clinically overt
      neurological deficit.

PMID- 23125301
TI  - Acute pyelonephritis and secondary bacteraemia caused by Veillonella during
      pregnancy.
AB  - We report a case of pyelonephritis and secondary bacteraemia caused by
      Veillonella species during pregnancy. Veillonella is part of the normal flora
      from the oral cavity, gut and vagina. However, because Veillonella is usually
      isolated from cultures of clinical specimens as part of commensal flora, it is
      frequently regarded as a contaminant. In the present case, Veillonella was
      isolated from the patient's urine and blood samples that showed evidence of
      pyelonephritis and secondary bacteraemia. We found that ureteral stenting is an
      extremely effective therapeutic option for pregnant woman with hydronephrosis and
      clear signs and symptoms of urosepsis.

PMID- 23125302
TI  - Unusual manifestations of Epstein-Barr virus infection in an 8-month-old male
      infant.
AB  - Severe acute hepatitis is a rare complication of Epstein-Barr virus (EBV)
      infection. The authors report a case of an 8-month-old male infant who presented
      with subacute fever and jaundice. The physical examination showed
      hepatosplenomegaly and ecchymoses on his abdomen, chest wall and extremities. He
      received vitamin K therapy and prednisolone, and he recovered well without
      further complications or sequelae. Although severe acute hepatitis is a rare
      complication of EBV infection, clinicians should recognise this condition in
      order to provide a prompt treatment.

PMID- 23125303
TI  - Paediatric type III dyslipidaemia: a case of vanishing hyperlipidaemia.
AB  - An 11-year-old girl presented with palmar and tuberoeruptive xanthomas, and
      elevated triglycerides and total cholesterol levels. She had an apolipoprotein
      E2/E2 genotype. A diagnosis of type III dyslipidaemia was made and the patient
      started on niacin, fenofibrate and salmon oil. At age 18, her lipid levels were
      well controlled with fenofibrate once weekly. At age 21, the fenofibrate was
      discontinued and her lipid profile has been normal for the last 4 years. This
      case history may be consistent with a transient dyslipidaemia.

PMID- 23125304
TI  - Sorafenib therapy decreases the clearance of thyrotropin.
AB  - OBJECTIVE: Thyroid function abnormalities are common during treatment with
      tyrosine kinase inhibitors such as sorafenib. Suggested causes are direct effects
      on thyroid tissue and increased extrathyroidal metabolism of serum thyroxine and
      3,5,3-triiodothyronine. We postulated that tyrosine kinase inhibitors may affect
      the peripheral metabolism of TSH as well. The effect of sorafenib on TSH
      clearance was studied. DESIGN: In a study of athyreotic patients on TSH
      suppression therapy, TSH concentrations were measured after recombinant human TSH
      (rhTSH) injections before and after 26 weeks of sorafenib therapy. METHODS:
      Before and after the last week of sorafenib therapy, 20 patients with progressive
      differentiated thyroid carcinoma received a standard dose regimen of two
      injections 0.9 mg rhTSH on two consecutive days. TSH concentrations were measured
      48 h (TSH(48 h)) and 96 h (TSH(96 h)) after the first rhTSH injection. The area
      under the curve (TSH-AUC), reflecting TSH content between 48 and 96 h following
      rhTSH administration, was calculated. RESULTS: TSH(48 h) levels (120.5 mU/l
      before vs 146.3 mU/l after; P=0.029), TSH(96 h) levels (22.0 mU/l before vs 35.5
      mU/l after; P=0.001), and TSH-AUC (142.7 vs 186.8 mU/l; P=0.001) were
      significantly higher after sorafenib treatment. Higher sorafenib doses were
      associated with increased changes in TSH(96 h) and TSH-AUC. In two patients, TSH
      levels after sorafenib therapy exceeded 200 mU/l. CONCLUSIONS: Sorafenib therapy
      is accompanied by higher rhTSH levels, probably due to a decreased TSH clearance.
      Further studies are recommended to clarify whether a decreased clearance of TSH
      is sorafenib specific.

PMID- 23125305
TI  - Will PAXgene substitute formalin? A morphological and molecular comparative study
      using a new fixative system.
AB  - Formalin fixation and paraffin embedding present the standard procedures for
      conserving clinical tissues for histological analysis. However, molecular
      analysis is impaired by the cross linking properties of formalin. The PAXgene
      tissue system (PreAnalytix, Switzerland) is a new formalin-free tissue collection
      device. AIMS: In this study we aimed to evaluate this new tissue preservation
      technique in comparison with formalin fixation and fresh frozen tissue samples.
      METHODS: 12 melanoma biopsy samples were divided and fixed simultaneously with
      formalin, PAXgene or fresh frozen in liquid nitrogen and analysed with regard to
      morphology, immunohistochemistry,  DNA and RNA content and quality. Markers of
      melanocytic differentiation and tumour cell proliferation were used. RESULTS:
      Morphology was well preserved in PAXPE samples. However, 5 out of 11
      immunohistochemical markers showed significantly lower overall staining and
      staining intensity with PAXPE tissues in comparison with formalin-fixed, paraffin
      embedded (FFPE). Increasing membrane permeability through adding a detergent did
      proportionally increase staining intensity in PAXPE samples. Amplification of
      different mRNA amplicons showed a direct relationship with the size of the
      amplicon with greater template integrity observed in PAXPE samples. Sequencing
      and mutational analysis of DNA samples were comparable for all the different
      fixation methods, while the level of DNA fragmentation seemed to be lower in
      PAXPE compared with FFPE tissues. CONCLUSIONS: The switch from formalin to
      PAXgene fixation would require a re-evaluation of immunohistochemical markers and
      staining procedures originally developed for FFPE tissues. Our data demonstrate
      that PAXPE fixation offers some advantages concerning molecular analysis.
      However, these advantages would not justify substituting formalin fixation in any
      routine pathology laboratory.

PMID- 23125306
TI  - Is there a surgeon or hospital volume-outcome relationship in off-pump coronary
      artery bypass surgery?
AB  - A best evidence topic was written according to a structured protocol. The
      question addressed was whether there is a surgeon or hospital volume-outcome
      relationship in patients undergoing off-pump coronary artery bypass surgery. A
      total of 281 papers were found using the reported searches, of which six
      represented the best evidence to answer the clinical question. The authors, date,
      journal, study type, population, main outcome measures and results are tabulated.
      The studies found analysed the outcomes of off-pump coronary artery bypass
      surgery in relation to surgeon or hospital volume and evaluated the presence of a
      volume-outcome relationship. Reported measures included mortality and major
      adverse cardiovascular and cerebrovascular events. The methodological quality and
      strength of each study for exploring volume-outcome relationships were
      quantitatively assessed using a predefined scoring system. Three studies analysed
      surgeon volume and three studies analysed hospital volume. The two largest and
      most recent studies presented a significant volume-outcome relationship in
      mortality and postoperative complications. Perhaps owing to the smaller sample
      size, this significant relationship in mortality was not observed in the four
      smaller studies; however, one of these studies demonstrated a significantly
      positive relationship for postoperative complications and another study
      demonstrated a similar significant relationship for the number of grafts and the
      degree of completeness of revascularization. While the volume-outcome
      relationship in coronary artery bypass graft surgery is very well-documented, the
      technically challenging nature of off-pump surgery, the length of the learning
      curve associated with the operation and the higher risk profile of patients
      undergoing off-pump surgery in comparison with routine on-pump surgery render
      these results difficult to interpret. Although our review does support the idea
      of a volume-outcome relationship in off-pump coronary artery bypass surgery, this
      relationship may not be so clearly defined and requires further analysis by
      higher-quality studies.

PMID- 23125307
TI  - A novel low-fidelity simulator for both mitral valve and tricuspid valve surgery:
      the surgical skills trainer for classic open and minimally invasive techniques.
AB  - OBJECTIVES: Simulators have been proven to equip trainee surgeons with better
      skills than the traditional, standard approach to skill development. The purpose
      of this study was to develop a low-fidelity, low-cost, reusable and portable
      simulation device, which could provide training in nearly the full range of
      mitral valve surgery techniques, in both the classic, open approach as well as
      the minimally invasive approach. METHODS: This novel simulator is made up of
      commonly available components. The basic elements are a classic baby bottle, with
      the associated feeding teat and screw ring, in combination with a sheet of dental
      dam. The detailed process for making this simulator is outlined in this article.
      Maximum suture tensile strength on the different components was tested with a
      digital force gauge. Reusability and the rate of wear as a result of suturing
      were documented. Total cost was calculated in euros (?). RESULTS: This study
      resulted in a simulation model very similar in size to the actual anatomical
      dimensions of the mitral valve. Various pathological conditions, according to
      Carpentier's Functional Classification, could be simulated. This led to the
      possibility of providing training in several mitral valve surgical techniques. As
      the model developed, it became clear that it could also be used to practice
      tricuspid valve surgery techniques. Maximum mean suture tensions on the silicone
      teat and dental dam were 42.11 and 11.15 N/m(2), respectively. The feeding teat
      started wearing after approximately 45 suture placements. Total cost of the study
      model was ?5.14. CONCLUSIONS: This relatively simple, low-cost, low-fidelity
      model can provide simulation training in nearly the full range of mitral valve
      and tricuspid valve surgical techniques, in both the classic open approach and
      the minimally invasive approach-and do so almost anywhere. Especially when used
      by young cardiothoracic surgeons in training, this model may contribute to the
      development of technical skills and procedural knowledge required for adequate
      performance in the operating room.

PMID- 23125308
TI  - Circumferential ascending aortic strain and aortic stenosis.
AB  - BACKGROUND: Two-dimensional speckle tracking (2D-ST) echocardiography for the
      measurement of circumferential ascending thoracic aortic strain (CAAS) in the
      context of aortic stenosis (AS) is not elucidated. Purpose This study assesses
      the thoracic ascending aortic deformation using 2D-ST echocardiography in AS
      patients. Population and methods Forty-five consecutive patients with an aortic
      valvular area (AVA) <=0.85 cm(2)/m(2) were included. Regarding aortic
      deformation, the global peak CAAS was the parameter used, and an average of six
      segments of arterial wall deformation was calculated. The corrected CAAS was
      calculated as the global CAAS/pulse pressure (PP). Aortic stiffness (beta2) index
      was assessed according to ln(Ps/Pd)/CAAS. The sample was stratified according to
      the stroke volume index (SVI) as: Group A (low flow, SVI <=35 mL/m(2); n = 19)
      and Group B (normal flow, SVI >35 mL/m(2); n = 26). RESULTS: The mean age was
      76.8 +/- 10.3 years, 53.3% were male, the mean indexed AVA was 0.43 +/- 0.15
      cm(2)/m(2), and the mean CAAS was 6.3 +/- 3.0%. The CAAS was predicted by SVI
      (beta = 0.31, P < 0.01) and by valvulo-arterial impedance (Zva). The corrected
      CAAS was correlated with the M-mode guided aortic stiffness index (beta1) (r = 
      0.39, P < 0.01), and was predicted by SVI, Zva, and systemic arterial compliance
      (beta = 0.15, P < 0.01). The beta2 index was significantly higher for the low
      flow patients (16.1 +/- 4.8 vs. 9.8 +/- 5.3, P < 0.01), and was predicted by SVI
      (beta -0.58, P < 0.01) and PP (beta = 0.17, P < 0.01). Global CAAS was more
      accurate to predict low flow than Zva, systolic function and systemic vascular
      resistance. CONCLUSION: In patients with moderate-to-severe aortic stenosis, SVI
      and LV afterload-related variables were the most important determinants of 2S-ST
      global CAAS.

PMID- 23125309
TI  - Airway obstruction due to aspiration of muddy water.
AB  - We report a case of complete airway obstruction due to aspiration of muddy water.
      An innovative approach to clear the airway is described, which may be a
      potentially life saving manoeuver in similar cases of suspected muddy water
      aspiration. 

PMID- 23125310
TI  - Toll-like receptor 4 activation reduces adrenal chromaffin cell excitability
      through a nuclear factor-kappaB-dependent pathway.
AB  - The adrenal medulla contains fenestrated capillaries that allow catecholamines
      and neuropeptides secreted by adrenal chromaffin cells (ACCs) to readily access
      the circulation. These capillaries may also allow bacterial products to enter the
      adrenal medulla and interact with ACCs during infection. One potential mediator
      of this interaction is toll-like receptor 4 (TLR-4), a pattern-recognition
      receptor that detects lipopolysaccharide (LPS) from Gram-negative bacteria.
      Evidence suggests that excitable cells can express TLR-4 and that LPS can
      modulate important neuronal and endocrine functions. The present study was
      therefore performed to test the hypothesis that TLR-4 activation by LPS affects
      ACC excitability and secretory output. RT-PCR revealed that TLR-4, cluster of
      differentiation 14, myeloid differentiation protein-2, and myeloid-derived factor
      88 are expressed within mouse adrenal medullae. TLR-4 immunoreactivity was
      observed within all tyrosine hydroxylase immunoreactive ACCs. Incubation of
      isolated ACCs in LPS dose dependently hyperpolarized the resting membrane
      potential and enhanced large conductance (BK) Ca(2+)-activated K(+) currents. LPS
      (10 MUg/ml) also increased rheobase, decreased the number of action potentials
      fired at rheobase, and reduced the percentage of ACCs exhibiting spontaneous and
      anodal break action potentials. Although catecholamine release was unaltered, LPS
      significantly reduced high-K(+)-stimulated neuropeptide Y release from isolated
      ACCs. LPS did not alter the excitability of ACCs from TLR-4(-/-) mice. Inhibition
      of nuclear factor-kappaB signaling with SC-514 (20 MUm) abolished the effects of
      LPS on ACC excitability. Our findings suggest that LPS acts at TLR-4 to reduce
      ACC excitability and neuropeptide Y release through an nuclear factor-kappaB
      dependent pathway.

PMID- 23125311
TI  - Contribution of endogenous glucocorticoids and their intravascular metabolism by
      11beta-HSDs to postangioplasty neointimal proliferation in mice.
AB  - Exogenous glucocorticoids inhibit neointimal proliferation in animals. We aimed
      to test the hypothesis that endogenous glucocorticoids influence neointimal
      proliferation; this may be mediated by effects on systemic risk factors or
      locally in vessels and modulated by either adrenal secretion or enzymes expressed
      in vessels that mediate local inactivation [11beta-hydroxysteroid dehydrogenase
      type II (11beta-HSD2) in endothelium] or regeneration [11beta-hydroxysteroid
      dehydrogenase type I (11beta-HSD1) in smooth muscle] of glucocorticoids. Femoral
      artery wire angioplasty was conducted in C57BL/6J, Apo-E(-/-), 11beta-HSD1(-/-),
      Apo-E, 11beta-HSD1(-/-) (double knockout), and 11beta-HSD2(-/-) mice after
      glucocorticoid administration, adrenalectomy, glucocorticoid or mineralocorticoid
      receptor antagonism, or selective 11beta-HSD1 inhibition. In C57BL/6J mice,
      neointimal proliferation was reduced by systemic or local glucocorticoid
      administration, unaffected by adrenalectomy, reduced by the mineralocorticoid
      receptor antagonist eplerenone, and increased by the glucocorticoid receptor
      antagonist RU38486. 11beta-HSD2 deletion had no effect on neointimal
      proliferation, with or without eplerenone. 11beta-HSD1 inhibition or deletion had
      no effect in chow-fed C57BL/6J mice but reduced neointimal proliferation in Apo
      E(-/-) mice on Western diet. Reductions in neointimal size were accompanied by
      reduced macrophage and increased collagen content. We conclude that
      pharmacological administration of glucocorticoid receptor agonists or of
      mineralocorticoid receptor antagonists may be useful in reducing neointimal
      proliferation. Endogenous corticosteroids induce beneficial glucocorticoid
      receptor activation and adverse mineralocorticoid receptor activation. However,
      manipulation of glucocorticoid metabolism has beneficial effects only in mice
      with exaggerated systemic risk factors, suggesting effects mediated primarily in
      liver and adipose rather than intravascular glucocorticoid signaling. Reducing
      glucocorticoid action with 11beta-HSD1 inhibitors that are being developed for
      type 2 diabetes appears not to risk enhanced neointimal proliferation.

PMID- 23125312
TI  - Corticosteroids, heart failure, and hypertension: a role for immune cells?
AB  - Aldosterone and its receptor the mineralocorticoid receptor (MR) are best known
      for their regulation of fluid and electrolyte homeostasis in epithelial cells.
      However, it is now clear that MR are also expressed in a broad range of
      nonepithelial tissues including the cardiovascular system. In the heart and
      vascular tissues, pathological activation of MR promotes cardiovascular
      inflammation and remodeling for which there is increasing evidence that
      macrophages and other immune cells (e.g. T cells and dendritic cells) play a
      significant role. While the glucocorticoids and their receptors have well
      described antiinflammatory actions in immune cells, a role for aldosterone and/or
      the MR in these cells is largely undefined. Emerging evidence, however, suggests
      that MR signaling may directly or indirectly promote proinflammatory responses in
      these immune cells. This review will discuss the current understanding of the
      role of corticosteroid receptors in macrophages and their effect on
      cardiovascular diseases involving inflammation.

PMID- 23125313
TI  - Involvement of GR and p300 in the induction of H6PD by cortisol in human amnion
      fibroblasts.
AB  - Human fetal membranes express 11beta-hydroxysteroid dehydrogenase type 1 (11beta
      HSD1), which reduces biologically inert cortisone to active cortisol and may
      provide an extraadrenal source of cortisol mediating fetal development and
      parturition. The reductase activity of 11beta-HSD1 depends on the availability of
      the cofactor reduced form of nicotinamide adenine dinucleotide phosphate (NADPH)
      derived from the enzymatic activity of hexose-6-phosphodehydrogenase (H6PD).
      Based on the feed-forward induction of 11beta-HSD1 by glucocorticoids in human
      fetal membranes, we hypothesize that glucocorticoids simultaneously induce H6PD
      in the fetal membranes. We found a parallel distribution of H6PD and 11beta-HSD1
      in the amnion, chorion, and decidua. In cultured human amnion fibroblasts, small
      interfering RNA-mediated knockdown of H6PD expression significantly attenuated
      the conversion of cortisone to cortisol. Cortisol (0.01-1 MUm) induced H6PD
      expression in a concentration-dependent manner, which was attenuated by
      glucocorticoid receptor (GR) antagonist RU486. Cortisol induced the expression of
      p300, a histone acetyltransferase, whereas C646, an inhibitor of p300, attenuated
      the induction of H6PD by cortisol. Coimmunoprecipitation revealed GR and p300 in
      the same nuclear protein complex upon cortisol stimulation. Chromatin
      immunoprecipitation showed that cortisol increased the binding of p300 and GR to
      H6PD promoter and the acetylation of histone 3 lysine 9 on the promoters. In
      conclusion, the induction of H6PD by cortisol requires the participation of GR
      and p300 as well as the acetylation of H3K9 by p300. This may be a prerequisite
      for the parallel induction of reductase activity of 11beta-HSD1 in human amnion
      fibroblasts in a feed-forward loop that may influence fetal development and the
      onset of parturition.

PMID- 23125314
TI  - The integrity of the plant Golgi apparatus depends on cell growth-controlled
      activity of GNL1.
AB  - Membrane traffic and organelle integrity in the plant secretory pathway depend on
      ARF-GTPases, which are activated by guanine-nucleotide exchange factors (ARF
      GEFs). While maintenance of conserved roles, evolution of unique functions as
      well as tissue-specific roles have been shown for a handful of plant ARF-GEFs, a
      fundamental yet unanswered question concerns the extent to which their function
      overlaps during cell growth. To address this, we have characterized pao, a novel
      allele of GNOM-like 1 (GNL1), a brefeldin A (BFA)-insensitive ARF-GEF, isolated
      through a confocal microscopy-based forward genetics screen of the Golgi in
      Arabidopsis thaliana. Specifically, we have analyzed the dependence of the
      integrity of trafficking routes and secretory organelles on GNL1 availability
      during expansion stages of cotyledon epidermal cells, an exquisite model system
      for vegetative cell growth analyses in intact tissues. We show that Golgi traffic
      is influenced largely by GNL1 availability at early stages of cotyledon cell
      expansion but by BFA-sensitive GEFs when cell growth terminates. These data
      reveal an unanticipated level of complexity in the biology of GNL1 by showing
      that its cellular roles are correlated with cell growth. These results also
      indicate that the cell growth stage is an important element weighting into
      functional analyses of the cellular roles of ARF-GEFs.

PMID- 23125315
TI  - Brassinosteroids regulate the differential growth of Arabidopsis hypocotyls
      through auxin signaling components IAA19 and ARF7.
AB  - Brassinosteroids (BRs) are an important class of phytohormones which regulates a
      wide range of physiological processes. Genetic and physiological studies have
      revealed that BR responses usually depend on an intact auxin signaling pathway.
      Here, we demonstrate that high BR concentration or enhanced BR signaling induce
      the differential growth of etiolated hypocotyls and result in the morphological
      changes, while auxin-resistant mutants, msg2 (dominant mutant of IAA19) and arf7,
      are insensitive to the BR effect and can partially suppress the phenotype of bzr1
      D (dominant mutant of BZR1 with enhanced BR signaling). Interestingly, BZR1
      protein can directly bind to the promoter regions of both IAA19 and ARF7,
      indicating that IAA19 and ARF7 mediate the BR-induced differential growth by
      serving as direct targets of BZR1. Systemic microarray analysis revealed that a
      number of BR-responsive genes showed reduced BR response in msg2, confirming that
      BR employs auxin signaling components IAA19 and ARF7 to modulate the specific
      downstream processes. These results provide informative clues on the crosstalk of
      BR-auxin signaling and the mechanisms of BR-auxin effects in regulating
      differential growth.

PMID- 23125316
TI  - Lachancea lanzarotensis sp. nov., an ascomycetous yeast isolated from grapes and
      wine fermentation in Lanzarote, Canary Islands.
AB  - During the characterization of the microbiota biodiversity associated with grapes
      and wineries in different bioclimatic conditions of the Canary Islands (Spain), a
      novel yeast species was isolated from Lanzarote, the driest wine-producing region
      of the archipelago. Seven strains isolated from grapes, microvinifications and
      wineries are described. Sequence analysis of the D1/D2 domain of the LSU rDNA
      gene and 5.8S-ITS regions revealed that the isolates were phylogenetically a
      member of the genus Lachancea and are closely related to Lachancea meyersii NRRL
      Y-27269(T) and Lachancea nothofagi NRRL Y-48670(T). On the basis of
      morphological, biochemical and physiological characterization and phylogenetic
      analysis, a novel ascosporogenous yeast species, Lachancea lanzarotensis sp.
      nov., is proposed. The type strain is L2C-15(T) ( = CBS 12615(T) = CECT 13066(T))
      which was isolated from grape berries of Vitis vinifera L. cv. Listan Negro red
      grape variety in Tinajo, Lanzarote. The MycoBank no. is MB 801390.

PMID- 23125317
TI  - Comamonas jiangduensis sp. nov., a biosurfactant-producing bacterium isolated
      from agricultural soil.
AB  - A novel biosurfactant-producing strain, designated YW1(T), was isolated from
      agricultural soil. Its taxonomic position was investigated using a polyphasic
      approach. The cells were short rods, Gram-negative, non-sporulating and motile.
      Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain
      YW1(T) was a member of the genus Comamonas, and showed highest sequence
      similarities to Comamonas aquatica LMG 2370(T) (98.5%), Comamonas kerstersii LMG
      3475(T) (97.7%) and Comamonas terrigena LMG 1253(T) (97.7%). Furthermore, DNA-DNA
      hybridization experiments against these three strains gave results that were
      clearly lower than 70% DNA-DNA similarity, and consequently confirmed that this
      new strain does not belong to a previously described species of the genus
      Comamonas. The major respiratory quinone was ubiquinone-8. The major fatty acids
      (>5%) were C16:0 (30.1%), summed feature 3 (C16:1omega6c and/or C16:1omega7c;
      25.4%), summed feature 8 (C18:1omega6c and/or C18:1omega7c; 15.3%), C17:0 cyclo
      (7.4%) and C14:0 (5.8%). The major polar lipids were diphosphatidylglycerol,
      phosphatidylglycerol, phosphatidylethanolamine, unknown phospholipids and unknown
      lipids. Based on the phylogenetic analysis, DNA-DNA hybridization, whole-cell
      fatty acid composition as well as biochemical characteristics, strain YW1(T) was
      clearly distinguishable from all species of the genus Comamonas with validly
      published names and should be classified as a representative of a novel species
      of the genus Comamonas, for which the name Comamonas jiangduensis sp. nov. is
      proposed. The type strain is YW1(T) (=CCTCC AB 2012033(T)=KACC 16697(T)).

PMID- 23125318
TI  - Acrocarpospora phusangensis sp. nov., isolated from a temperate peat swamp forest
      soil.
AB  - A novel actinomycete, strain PS33-18(T), that formed club-shaped and spherical
      structures borne on the tip of the aerial mycelia was isolated from a temperate
      peat swamp forest soil in Phu-Sang National Park, Phayao Province, Thailand. The
      isolate contained glutamic acid, alanine and meso-diaminopimelic acid in the cell
      wall peptidoglycan. The whole-cell sugars of strain PS33-18(T) were glucose,
      madurose, mannose, rhamnose and ribose. The characteristic phospholipids were
      phosphatidylethanolamine, phosphatidylmethylethanolamine, hydroxy
      phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol,
      phosphatidylinositol, phosphatidylinositol mannosides and ninhydrin-positive
      phosphoglycolipids. The predominant menaquinone was MK-9(H4). The major cellular
      fatty acids were C17:1omega8c, iso-C16:0 and C16:0. The G+C content of the
      genomic DNA of strain PS33-18(T) was 71.0 mol%. Phylogenetic analysis using 16S
      rRNA gene sequences revealed that strain PS33-18(T) should be classified in the
      genus Acrocarpospora. The level of similarity between this strain and the closely
      related species Acrocarpospora macrocephala NBRC 16266(T) was 98.3%,
      Acrocarpospora pleiomorpha NBRC 16267(T) was 97.9%, Acrocarpospora corrugata NBRC
      13972(T) was 97.6%, Herbidospora sakaeratensis NBRC 102641(T) was 97.6% and
      Planotetraspora kaengkrachanensis NBRC 104272(T) was 97.3%. DNA-DNA hybridization
      results and physiological and biochemical properties indicated that strain PS33
      18(T) could be distinguished readily from its closest phylogenetic relatives. On
      the basis of these phenotypic and genotypic data, this strain represents a novel
      species, for which the name Acrocarpospora phusangensis sp. nov. is proposed. The
      type strain is PS33-18(T) (=BCC 46906(T)=NBRC 108782(T)).

PMID- 23125319
TI  - Salinisphaera japonica sp. nov., a moderately halophilic bacterium isolated from
      the surface of a deep-sea fish, Malacocottus gibber, and emended description of
      the genus Salinisphaera.
AB  - A moderately halophilic, slightly acidophilic, aerobic bacterium, designated
      strain YTM-1(T), was isolated from the body surface of Malacocottus gibber. Cells
      were Gram-stain-negative, short rods or cocci, approximately 0.9-1.1 um long and
      1.0-1.8 um wide. Strain YTM-1(T) was able to grow with 1-30% NaCl (optimum, 7.5
      10%, w/v), at 4-30  degrees C (optimum, 20-25  degrees C) and at pH 3.8-9.5
      (optimum, pH 5.0-5.5). Phylogenetic analysis based on 16S rRNA gene sequence
      similarities showed that strain YTM-1(T) belonged to the genus Salinisphaera with
      low similarity values to the type strains of recognized species of this genus
      (<94.8-94.4%). The polar lipids of strain YTM-1(T) consisted of
      diphosphatidylglycerol, phosphatidylcholine, phosphatidylglycerol,
      phosphatidylethanolamine, phosphatidylserine, three unknown phospholipids and one
      unknown lipid. The predominant isoprenoid quinone was Q-8. The major fatty acids
      were C19:0omega8c cyclo, C18:1omega7c, C16:1omega5c and C16:0. The DNA G+C
      content of strain YTM-1(T) was 67.3 mol%. These phylogenetic, physiological and
      chemotaxonomic data indicated that strain YTM-1(T) represents a novel species of
      the genus Salinisphaera, for which the name Salinisphaera japonica sp. nov. is
      proposed. The type strain is YTM-1(T) (=JCM 18087(T)=CECT 8012(T)). An emended
      description of the genus Salinisphaera is also proposed.

PMID- 23125320
TI  - Sphingopyxis indica sp. nov., isolated from a high dose point
      hexachlorocyclohexane (HCH)-contaminated dumpsite.
AB  - A Gram-stain-negative, aerobic, non-motile, non-spore-forming, rod-shaped and
      light-yellow-pigmented bacterium, designated DS15(T), was isolated from a soil
      sample collected from a hexachlorocyclohexane dumpsite in Lucknow, Uttar Pradesh,
      India. Strain DS15(T) showed highest 16S rRNA gene sequence similarity to
      Sphingopyxis panaciterrulae DCY34(T) (98.7%) and Sphingopyxis soli BL03(T)
      (98.0%). The 16S rRNA gene sequence similarity between strain DS15(T) and species
      of genus Sphingopyxis with validly published names ranged from 92.5% to 98.7%.
      The DNA G+C content of strain DS15(T) was 67.5 mol%. The chemotaxonomic markers
      in strain DS15(T) were consistent with its classification in the genus
      Sphingopyxis, i.e. Q-10 as the major ubiquinone and summed feature 8
      (C18:1omega7c/C18:1omega9c), C17:1omega6c, summed feature 3
      (C16:1omega7c/C16:1omega6c), C14:0 2-OH, C15:0 2-OH, C16:0 and C17:1omega8c as
      the predominant fatty acids. The major polar lipids of strain DS15(T) were
      phosphatidylethanolamine (PE), diphosphatidylglycerol (DPG), phosphatidylcholine
      (PC), phosphatidylglycerol (PG) and sphingoglycolipids (SGL) and spermidine was
      detected as the major polyamine. Phylogenetic analysis, DNA-DNA hybridization,
      and chemotaxonomic and phenotypic analysis support the conclusion that strain
      DS15(T) represents a novel species within the genus Sphingopyxis, for which the
      name Sphingopyxis indica is proposed. The type strain is DS15(T) (=MTCC
      9455(T)=CCM 7542(T)=MCC 2023(T)).

PMID- 23125321
TI  - Halopelagius fulvigenes sp. nov., a halophilic archaeon isolated from a lake.
AB  - Two extremely halophilic archaea, designated YIM 94188(T) and YIM 94189, were
      isolated from Qijiaojing lake in Xinjiang province, north-west China and
      subjected to taxonomic characterization using a polyphasic approach. The cells of
      the two strains were coccoid, non-motile and Gram-stain-negative. Colonies were
      pink-white-pigmented and aerobic. Growth occurred at 10-30% (w/v) NaCl, 20-55 
      degrees C and pH 6.0-8.0 (optimum: 20-25% NaCl, 37-42  degrees C, pH 6.5-7.0).
      Magnesium was necessary for growth in the range of 0.2-1.2 M. Phylogenetic
      analysis based on the 16S rRNA gene sequences indicated that the two strains
      belonged to the genus Halopelagius showing 98.5% sequence similarity to the
      closest phylogenetic neighbour, Halopelagius inordinatus RO5-2(T). In addition,
      the DNA-DNA hybridization values of strains YIM 94188(T) and YIM 94189 to
      Halopelagius inordinatus RO5-2(T) were 35.7% and 37.7%, respectively. Polar lipid
      analyses revealed that the two strains contained phosphatidylglycerol (PG),
      phosphatidylglycerol phosphate methyl ester (PGP-Me), sulfated mannosyl glucosyl
      diether (S-DGD-1) and mannosyl glucosyl diether (DGD-1). The DNA G+C contents of
      strains YIM 94188(T) and YIM 94189 were 66.3 mol% and 64.6 mol%, respectively. On
      the basis of physiological and chemotaxonomic data, and phylogenetic analysis,
      strains YIM 94188(T) and YIM 94189 were classified as representing a novel
      species in the genus Halopelagius. The name Halopelagius fulvigenes sp. nov. is
      proposed, with YIM 94188(T) (=CCTCC AB 2010456(T)=JCM 17506(T)) as the type
      strain.

PMID- 23125322
TI  - Why not a shot of prevention?

PMID- 23125323
TI  - Q: Should N-acetylcysteine be used routinely to prevent contrast-induced acute
      kidney injury?

PMID- 23125324
TI  - A rash after streptococcal infection.

PMID- 23125325
TI  - Tattooing: medical uses and problems.
AB  - Decorative tattooing is a custom thousands of years old and is growing in
      popularity today. Medical professionals may be less familiar with its medical
      applications-medical alert tattooing, reconstructive and cosmetic applications,
      endoscopic tattooing, corneal tattooing, tattooing in radiation oncology, and
      uses in forensic medicine. We review current medically related tattooing
      applications and discuss their potential risks and benefits.

PMID- 23125326
TI  - Emergency contraception: separating fact from fiction.
AB  - Rates of unintended pregnancy and abortion are high, yet many doctors do not feel
      comfortable discussing emergency contraception with patients, even in cases of
      sexual assault. Since the approval of ulipristal acetate (ella) for emergency
      contraception, there has been even more confusion and controversy. This article
      reviews various emergency contraceptive options, their efficacy, and special
      considerations for use, and will attempt to clarify myths surrounding this topic.

PMID- 23125327
TI  - 2012-2013 influenza update: hitting a rapidly moving target.
AB  - From the deadly 2009 influenza A H1N1 pandemic to the looming threat of bird flu
      H5N1, the recent outbreak of swine flu H3N2v at agriculture fairs, and the
      emergence of drug-resistant H1N1, we are constantly challenged by influenza
      viruses. Vaccination remains the main strategy for prevention. With the knowledge
      gained from past pandemics, an adequate vaccine supply, and an updated preventive
      strategy, we are in a better position to face the challenge.

PMID- 23125328
TI  - Nail pigmentation and fatigue.

PMID- 23125329
TI  - Detecting and managing hereditary colorectal cancer syndromes in your practice.
AB  - Hereditary syndromes account for 5% to 10% of cases of colorectal cancer. In
      clinical practice, patients with these syndromes need to be identified to ensure
      that they and their families receive genetic counseling and testing and
      appropriate risk-reducing treatment. Genetic testing can offer a precise
      diagnosis. It allows for risk stratification and focused management and
      surveillance.

PMID- 23125330
TI  - Androgen deficiency in older men: indications, advantages, and pitfalls of
      testosterone replacement therapy.
AB  - The decline in testosterone with age has been associated with specific physical
      changes that affect quality of life and life expectancy, although a cause-and
      effect relationship is yet to be established. While female menopause is rapid and
      well described, "male menopause" or androgen decline in older men is gradual and
      marked by nonspecific symptoms. This makes diagnosis of true testosterone
      deficiency and prediction of response to testosterone replacement therapy (TRT)
      challenging. This article reviews androgen decline in men, focusing on those over
      age 40, and covers symptoms, indications, contraindications,diagnosis,
      treatments, and the risks and benefits of treatment [corrected].

PMID- 23125331
TI  - Plasmacytoid dendritic cells have a cytokine-producing capacity to enhance ICOS
      ligand-mediated IL-10 production during T-cell priming.
AB  - Plasmacytoid dendritic cells (pDCs) have the potential to prime CD4(+) T-cells to
      differentiate into IL-10-producing T regulatory cells through preferential
      expression of inducible co-stimulatory ligand (ICOS-L). Although pDCs produce
      cytokines such as type-I IFNs, TNF-alpha, or IL-6 accompanying up-regulation of
      ICOS-L expression during activation in response to toll-like receptor (TLR)
      ligands or IL-3, the roles of the pDC-derived cytokines in T-cell priming remain
      largely elusive. Therefore, we investigated the functional involvement of these
      cytokines in generating IL-10-producing T regulatory cells. We found that either
      IFN-alpha or IL-6 enhanced the pDC- or ICOS-L-driven generation of IL-10
      producing T-cells from naive CD4(+) T-cells and their regulatory functions.
      However, IFN-alpha stimulation in the absence of ICOS-L showed only a marginal
      tendency to increase the T-cell production of IL-10 and thus pDC-derived type-I
      IFNs in response to CpG could function together with ICOS-L. In addition, IL-6
      functioned to generate IL-10-producing T-cells only on T-cell priming by pDCs
      activated by IL-3 or under IL-4-mediated T(h)2 conditions. Thus, type-I IFNs and
      IL-6 act as supplementary factors for the ICOS-L-dependent IL-10-producing T-cell
      differentiation in pDCs activated along the TLR-dependent and IL-3-dependent
      pathways, respectively. We also showed that pDC-derived TNF-alpha induced ICOS-L
      expression on pDCs in an autocrine manner and that IL-6 promoted ICOS expression
      on T-cells, contributing to the ICOS/ICOS-L-mediated T-cell response. Our results
      suggest that the ICOS-L-mediated tolerogenic pDC function in adaptive immunity is
      backed up by the elaborate cytokine-producing ability of pDCs.

PMID- 23125332
TI  - Relationship between orbital optic nerve axon counts and retinal nerve fiber
      layer thickness measured by spectral domain optical coherence tomography.
AB  - PURPOSE: We determined the relationship between total optic nerve axon counts and
      peripapillary retinal nerve fiber layer thickness (RNFLT) measured in vivo by
      spectral domain optical coherence tomography (SDOCT). METHODS: A total of 22
      rhesus macaques had three or more baseline measurements in both eyes of
      peripapillary RNFLT made by SDOCT. Laser photocoagulation then was applied to the
      trabecular meshwork of one eye to induce chronic unilateral IOP elevation. SDOCT
      measurements of RNFLT continued approximately every two weeks until the
      predefined study endpoint was reached in each animal. At endpoint, animals were
      sacrificed and the optic nerve was sampled approximately 2 mm behind the globe to
      obtain thin sections for histologic processing and automated axon counting across
      100% of the optic nerve cross-sectional area. RESULTS: At the final imaging
      session, the average loss of RNFLT was 20 +/- 21%, ranging from essentially no
      loss to nearly 65% loss. Total optic nerve axon count in control eyes ranged from
      812,478 to 1,280,474. The absolute number of optic nerve axons was related
      linearly to RNFLT (axon count = 12,336 * RNFLT((MUm)) - 257,050, R(2) = 0.65, P <
      0.0001), with a Pearson correlation coefficient of 0.81. There also was a strong
      linear relationship between relative optic nerve axon loss (glaucomatous-to
      control eye) and relative RNFLT at the final imaging session, with a slope close
      to unity but a significantly negative intercept (relative axon loss((%)) = 1.05 *
      relative RNFLT loss((%)) - 14.4%, R(2) = 0.75, P < 0.0001). The negative
      intercept was robust to variations of fitted model because relative axon loss was
      -14% on average for all experimental glaucoma (EG) eyes within 6% (measurement
      noise) of zero relative loss. CONCLUSIONS: There is a strong linear relationship
      between total optic nerve axon count and RNFLT measured in vivo by SDOCT.
      However, substantial loss of optic nerve axons (~10%-15%) exists before any loss
      of RNFLT manifests and this discrepancy persists systematically throughout a wide
      range of damage.

PMID- 23125334
TI  - State-level uterine corpus cancer incidence rates corrected for hysterectomy
      prevalence, 2004 to 2008.
AB  - BACKGROUND: The interpretation of uterine cancer rates is hindered by the
      inclusion of women whose uterus has been surgically removed in the population at
      risk. Hysterectomy prevalence varies widely by state and race/ethnicity,
      exacerbating this issue. METHODS: We estimated hysterectomy-corrected, age
      adjusted uterine corpus cancer incidence rates by race/ethnicity for 49 states
      and the District of Columbia during 2004 to 2008 using case counts obtained from
      population-based cancer registries; population data from the U.S. Census Bureau;
      and hysterectomy prevalence data from the Behavioral Risk Factor Surveillance
      System. Corrected and uncorrected incidence rates were compared with regard to
      geographic and racial/ethnic disparity patterns and the association with obesity.
      RESULTS: Among non-Hispanic Whites, uterine cancer incidence rates (per 100,000
      woman-years) uncorrected for hysterectomy prevalence ranged from 17.1 in
      Louisiana to 32.1 in New Jersey, mirrored regional hysterectomy patterns, and
      were not correlated with obesity prevalence (Pearson correlation coefficient, r =
      0.06, two-sided P = 0.68). In comparison, hysterectomy-corrected rates were
      higher by a minimum of 30% (District of Columbia) to more than 100% (Mississippi,
      Louisiana, Alabama, and Oklahoma), displayed no discernible geographic pattern,
      and were moderately associated with obesity (r = 0.37, two-sided P = 0.009). For
      most states, hysterectomy correction diminished or reversed the Black/White
      deficit and accentuated the Hispanic/White deficit. CONCLUSION: Failure to adjust
      uterine cancer incidence rates for hysterectomy prevalence distorts true
      geographic and racial patterns and substantially underestimates the disease
      burden, particularly for Southern states. IMPACT: Correction for hysterectomy is
      necessary for the accurate evaluation of uterine cancer rates.

PMID- 23125333
TI  - Common genetic variation of the calcium-sensing receptor and lethal prostate
      cancer risk.
AB  - BACKGROUND: Bony metastases cause substantial morbidity and mortality from
      prostate cancer (PCa). The calcium-sensing receptor (CaSR) is expressed on
      prostate tumors and may participate in bone metastases development. We assessed
      whether (i) common genetic variation in CaSR was associated with PCa risk and
      (ii) these associations varied by calcium intake or plasma 25-hydroxyvitamin D
      [25(OH)D] levels. METHODS: We included 1,193 PCa cases and 1,244 controls nested
      in the prospective Health Professionals Follow-up Study (1993-2004). We genotyped
      18 CaSR single-nucleotide polymorphism (SNPs) to capture common variation. The
      main outcome was risk of lethal PCa (n = 113); secondary outcomes were overall (n
      = 1,193) and high-grade PCa (n = 225). We used the kernel machine approach to
      conduct a gene-level multimarker analysis and unconditional logistic regression
      to compute per-allele ORs and 95% confidence intervals (CI) for individual SNPs.
      RESULTS: The joint association of SNPs in CaSR was significant for lethal PCa (P
      = 0.04); this association was stronger in those with low 25(OH)D (P = 0.009). No
      individual SNPs were associated after considering multiple testing; three SNPs
      were nominally associated (P < 0.05) with lethal PCa with ORs (95% CI) of
      0.65(0.42-0.99): rs6438705; 0.65(0.47-0.89): rs13083990; and 1.55(1.09-2.20):
      rs2270916. The three nonsynonymous SNPs (rs1801725, rs1042636, and rs1801726)
      were not significantly associated; however, the association for rs1801725 was
      stronger in men with low 25(OH)D [OR(95%CI): 0.54(0.31-0.95)]. There were no
      significant associations with overall or high-grade PCa. CONCLUSIONS: Our
      findings indicate that CaSR may be involved in PCa progression. IMPACT: Further
      studies investigating potential mechanisms for CaSR and PCa, including bone
      remodeling and metastases are warranted.

PMID- 23125335
TI  - Forelimb kinematics during swimming in the pig-nosed turtle, Carettochelys
      insculpta, compared with other turtle taxa: rowing versus flapping, convergence
      versus intermediacy.
AB  - Animals that swim using appendages do so by way of rowing and/or flapping
      motions. Often considered discrete categories, rowing and flapping are more
      appropriately regarded as points along a continuum. The pig-nosed turtle,
      Carettochelys insculpta, is unusual in that it is the only freshwater turtle to
      have limbs modified into flippers and swim via synchronous forelimb motions that
      resemble dorsoventral flapping, traits that evolved independently from their
      presence in sea turtles. We used high-speed videography to quantify forelimb
      kinematics in C. insculpta and a closely related, highly aquatic rower (Apalone
      ferox). Comparisons of our new data with those previously collected for a
      generalized freshwater rower (Trachemys scripta) and a flapping sea turtle
      (Caretta caretta) allow us to: (1) more precisely quantify and characterize the
      range of limb motions used by flappers versus rowers, and (2) assess whether the
      synchronous forelimb motions of C. insculpta can be classified as flapping (i.e.
      whether they exhibit forelimb kinematics and angles of attack more similar to
      closely related rowing species or more distantly related flapping sea turtles).
      We found that the forelimb kinematics of previously recognized rowers (T. scripta
      and A. ferox) were most similar to each other, but that those of C. insculpta
      were more similar to rowers than to flapping C. caretta. Nevertheless, of the
      three freshwater species, C. insculpta was most similar to flapping C. caretta.
      'Flapping' in C. insculpta is achieved through humeral kinematics very different
      from those in C. caretta, with C. insculpta exhibiting significantly more
      anteroposterior humeral motion and protraction, and significantly less
      dorsoventral humeral motion and depression. Based on several intermediate
      kinematic parameters and angle of attack data, C. insculpta may in fact represent
      a synchronous rower or hybrid rower-flapper, suggesting that traditional views of
      C. insculpta as a flapper should be revised.

PMID- 23125336
TI  - Thermal effects on motor control and in vitro muscle dynamics of the ballistic
      tongue apparatus in chameleons.
AB  - Temperature strongly affects whole-organism performance through its effect on
      muscle contractile rate properties, but movements powered by elastic recoil are
      liberated from much of the performance decline experienced by muscle-powered
      movements at low temperature. We examined the motor control and muscle
      contractile physiology underlying an elastically powered movement - tongue
      projection in chameleons - and the associated muscle powered retraction to test
      the premise that the thermal dependence of muscle contractile dynamics is
      conserved. We further tested the associated hypothesis that motor control
      patterns and muscle contractile dynamics must change as body temperature varies,
      despite the thermal robustness of tongue-projection performance. We found that,
      over 14-26 degrees C, the latency between the onset of the tongue projector
      muscle activity and tongue projection was significantly affected by temperature
      (Q(10) of 2.56), as were dynamic contractile properties of the tongue projector
      and retractor muscles (Q(10) of 1.48-5.72), supporting our hypothesis that
      contractile rates slow with decreasing temperature and, as a result, activity
      durations of the projector muscle increase at low temperatures. Over 24-36
      degrees C, thermal effects on motor control and muscle contractile properties
      declined, indicating that temperature effects are more extreme across lower
      temperature ranges. Over the entire 14-36 degrees C range, intensity of muscle
      activity for the tongue muscles was not affected by temperature, indicating that
      recruitment of motor units in neither muscle increases with decreasing
      temperature to compensate for declining contractile rates. These results reveal
      that specializations in morphology and motor control, not muscle contractile
      physiology, are responsible for the thermal robustness of tongue projection in
      chameleons.

PMID- 23125337
TI  - Temperature-dependent sex determination modulates cardiovascular maturation in
      embryonic snapping turtles Chelydra serpentina.
AB  - We investigated sex differences in cardiovascular maturation in embryos of the
      snapping turtle Chelydra serpentina, a species with temperature-dependent sex
      determination. One group of eggs was incubated at 26.5 degrees C to produce
      males. Another group of eggs was incubated at 26.5 degrees C until embryos
      reached stage 17; eggs were then shifted to 31 degrees C for 6 days to produce
      females, and returned to 26.5 degrees C for the rest of embryogenesis. Thus,
      males and females were at the same temperature when autonomic tone was determined
      and for most of development. Cholinergic blockade increased resting blood
      pressure (P(m)) and heart rate (f(H)) in both sexes at 75% and 90% of incubation.
      However, the magnitude of the f(H) response was enhanced in males compared with
      females at 90% of incubation. beta-adrenergic blockade increased P(m) at 75% of
      incubation in both sexes but had no effect at 90% of incubation. beta-adrenergic
      blockade reduced f(H) at both time points but produced a stronger response at 90%
      versus 75% of incubation. We found that alpha-adrenergic blockade decreased P(m)
      in both sexes at 75% and 90% of incubation and decreased f(H) at 75% of
      incubation in both sexes. At 90% of incubation, f(H) decreased in females but not
      males. Although these data clearly demonstrate sexual dimorphism in the autonomic
      regulation of cardiovascular physiology in embryos, further studies are needed to
      test whether differences are caused by endocrine signals from gonads or by a
      hormone-independent temperature effect.

PMID- 23125338
TI  - Information content of visual scenes influences systematic search of desert ants.
AB  - Many animals - including insects - navigate visually through their environment.
      Solitary foraging desert ants are known to acquire visual information from the
      surrounding panorama and use it to navigate along habitual routes or to pinpoint
      a goal such as the nest. Returning foragers that fail to find the nest entrance
      engage in searching behaviour, during which they continue to use vision. The
      characteristics of searching behaviour have typically been investigated in
      unfamiliar environments. Here we investigated in detail the nest-searching
      behaviour of Melophorus bagoti foragers within the familiar visual environment of
      their nest. First, by relating search behaviour to the information content of
      panoramic (360 deg) images, we found that searches were more accurate in visually
      cluttered environments. Second, as observed in unfamiliar visual surrounds,
      searches were dynamic and gradually expanded with time, showing that nest
      pinpointing is not rigidly controlled by vision. Third, contrary to searches
      displayed in unfamiliar environments, searches observed here could be modelled as
      a single exponential search strategy, which is similar to a Brownian walk, and
      there was no evidence of a Levy walk. Overall, our results revealed that
      searching behaviour is remarkably flexible and varies according to the relevance
      of information provided by the surrounding visual scenery.

PMID- 23125339
TI  - Differential strain patterns of the human Achilles tendon determined in vivo with
      freehand three-dimensional ultrasound imaging.
AB  - The human Achilles tendon (AT) has often been considered to act as a single
      elastic structure in series with the muscles of the triceps surae. As such it has
      been commonly modelled as a Hookean spring of uniform stiffness. However, the
      free AT and the proximal AT have distinctly different structures that lend
      themselves to different elastic properties. This study aimed to use three
      dimensional freehand ultrasound imaging to determine whether the proximal AT and
      the free AT exhibit different elastic behaviour during sub-maximal, fixed-end
      contractions of the triceps surae. Six male and five female participants (mean +/
      s.d. age=27 +/- 5 years) performed fixed position contractions of the plantar
      flexors on an isokinetic dynamometer at 50% of their maximum voluntary
      contraction in this position. Freehand three-dimensional ultrasound imaging was
      used to reconstruct the free-tendon and proximal AT at rest and during
      contraction. The free-tendon exhibited significantly (P=0.03) greater
      longitudinal strain (5.2 +/- 1.7%) than the proximal AT (2.6 +/- 2.0%). The
      lesser longitudinal strain of the proximal AT was linked to the fact that it
      exhibited considerable transverse (orthogonal to the longitudinal direction)
      strains (5.0 +/- 4%). The transverse strain of the proximal AT is likely due to
      the triceps surae muscles bulging upon contraction, and thus the level of bulging
      may influence the elastic behaviour of the proximal AT. This might have
      implications for the understanding of triceps surae muscle-tendon interaction
      during locomotion, tendon injury mechanics and previous measurements of AT
      elastic properties.

PMID- 23125340
TI  - More than a feeling: incidental learning of array geometry by blindfolded adult
      humans revealed through touch.
AB  - View-based matching theories of orientation suggest that mobile organisms encode
      a visual memory consisting of a visual panorama from a target location and
      maneuver to reduce discrepancy between current visual perception and this stored
      visual memory to return to a location. Recent success of such theories to explain
      the orientation behavior of insects and birds raises questions regarding the
      extent to which such an explanation generalizes to other species. In the present
      study, we attempted to determine the extent to which such view-based matching
      theories may explain the orientation behavior of a mammalian species (in this
      case adult humans). We modified a traditional enclosure orientation task so that
      it involved only the use of the haptic sense. The use of a haptic orientation
      task to investigate the extent to which view-based matching theories may explain
      the orientation behavior of adult humans appeared ideal because it provided an
      opportunity for us to explicitly prohibit the use of vision. Specifically, we
      trained disoriented and blindfolded human participants to search by touch for a
      target object hidden in one of four locations marked by distinctive textural cues
      located on top of four discrete landmarks arranged in a rectangular array.
      Following training, we removed the distinctive textural cues and probed the
      extent to which participants learned the geometry of the landmark array. In the
      absence of vision and the trained textural cues, participants showed evidence
      that they learned the geometry of the landmark array. Such evidence cannot be
      explained by an appeal to view-based matching strategies and is consistent with
      explanations of spatial orientation related to the incidental learning of
      environmental geometry.

PMID- 23125341
TI  - The energy cost of voluntary running in the weasel Mustela nivalis.
AB  - The small size and elongate shape of weasels (Mustela nivalis) probably evolved
      to facilitate movement within the burrow systems of prey species, but result in
      high energy costs of thermoregulation. In this study we measured metabolic rates
      of weasels during voluntary locomotion to determine whether energy costs of
      transport are also high in these unusually shaped mammals. In addition, we
      measured the lower and upper limits of aerobic metabolism [resting metabolic rate
      (RMR) and maximal oxygen consumption in forced exercise (V(O(2),max))], and used
      the wide size range of adult weasels to investigate the intraspecific scaling of
      energy metabolism. Finally, we combined measurements of energy use during running
      with radiotracking and doubly labeled water data from free-living weasels to
      estimate the importance of locomotor costs in daily energy budgets. We found that
      weasels have higher than predicted costs of running, largely because of an
      elevated intercept of the speed versus metabolic rate relationship. Running costs
      were strongly affected by the approximately fourfold range of body size in
      adults. As reported in other studies, the RMR of weasels was considerably higher
      than predicted from body mass. Maximal oxygen consumption was also higher than
      predicted, but factorial aerobic scope (V(O(2),max)/RMR) was within the normal
      range for mammals. Intraspecific mass scaling of RMR and V(O(2),max) did not
      differ from typical interspecific mammalian allometries. In wild weasels,
      locomotor costs comprised roughly 5% of daily energy expenditures; this low value
      was primarily a result of short travel times and distances.

PMID- 23125342
TI  - Low-pass filters and differential tympanal tuning in a paleotropical bushcricket
      with an unusually low frequency call.
AB  - Low-frequency sounds are advantageous for long-range acoustic signal
      transmission, but for small animals they constitute a challenge for signal
      detection and localization. The efficient detection of sound in insects is
      enhanced by mechanical resonance either in the tracheal or tympanal system before
      subsequent neuronal amplification. Making small structures resonant at low sound
      frequencies poses challenges for insects and has not been adequately studied.
      Similarly, detecting the direction of long-wavelength sound using interaural
      signal amplitude and/or phase differences is difficult for small animals.
      Pseudophylline bushcrickets predominantly call at high, often ultrasonic
      frequencies, but a few paleotropical species use lower frequencies. We
      investigated the mechanical frequency tuning of the tympana of one such species,
      Onomarchus uninotatus, a large bushcricket that produces a narrow bandwidth call
      at an unusually low carrier frequency of 3.2 kHz. Onomarchus uninotatus, like
      most bushcrickets, has two large tympanal membranes on each fore-tibia. We found
      that both these membranes vibrate like hinged flaps anchored at the dorsal wall
      and do not show higher modes of vibration in the frequency range investigated
      (1.5-20 kHz). The anterior tympanal membrane acts as a low-pass filter,
      attenuating sounds at frequencies above 3.5 kHz, in contrast to the high-pass
      filter characteristic of other bushcricket tympana. Responses to higher
      frequencies are partitioned to the posterior tympanal membrane, which shows
      maximal sensitivity at several broad frequency ranges, peaking at 3.1, 7.4 and
      14.4 kHz. This partitioning between the two tympanal membranes constitutes an
      unusual feature of peripheral auditory processing in insects. The complex
      tracheal shape of O. uninotatus also deviates from the known tube or horn shapes
      associated with simple band-pass or high-pass amplification of tracheal input to
      the tympana. Interestingly, while the anterior tympanal membrane shows
      directional sensitivity at conspecific call frequencies, the posterior tympanal
      membrane is not directional at conspecific frequencies and instead shows
      directionality at higher frequencies.

PMID- 23125343
TI  - Condition-dependent strategies of eggshell pigmentation: an experimental study of
      Japanese quail (Coturnix coturnix japonica).
AB  - A relationship has been suggested between eggshell colour and female body
      condition based on the opposing antioxidant properties of the two main eggshell
      pigments: the antioxidant biliverdin (blue-green) and the pro-oxidant
      protoporphyrin (brown). We hypothesized that experimentally food-restricted
      females with low antioxidant capacity would deposit more protoporphyrin and less
      biliverdin in their eggshells, resulting in eggshells of reduced brightness but
      increased colour intensity. Two eggs were collected at the beginning and two at
      the end of a 2 week period from each of 24 female Japanese quails that were
      either food restricted or receiving ad libitum food (i.e. controls) during that
      time. Reflectance spectra were recorded and analysed using spectral shape
      descriptors, chromatic and achromatic contrasts were computed accounting for
      avian visual sensitivities, and eggshell pigments were quantified. We examined
      both spot and background pigmentation and found no significant effect of food
      restriction on eggshell reflectance. However, food-restricted females in lower
      body condition increased the deposition of protoporphyrin and decreased the
      amount of biliverdin invested in their eggshells. We hypothesize that in species
      laying brown-spotted eggshells, females modulate eggshell pigment investment in
      response to their body condition. According to this hypothesis, we predict that
      females maintain eggshell colour to limit visible changes that could be detected
      by predators and thereby conceal their eggs, although this work has yet to be
      conducted. We suggest that further experimental work on egg camouflage under
      different environmental conditions will elaborate on the process of pigment
      deposition and the physiological costs to females of laying heavily pigmented
      eggshells.

PMID- 23125344
TI  - Social status-dependent modulation of LG-flip habituation in the crayfish.
AB  - Strong stimuli applied to the tailfan of the crayfish Procambarus clarkii evoked
      lateral giant interneurone (LG)-mediated tailflips. When the sensory stimulus was
      applied repeatedly, the response of the LG habituated until it failed to give
      rise to a spike. We found that this LG-flip habituation was dependent on social
      status. With a short interstimulus interval of 5 s, the rate of habituation of
      the LG in both socially dominant and subordinate crayfish was lower than that in
      socially isolated animals. By contrast, with a long interstimulus interval of 60
      s, the rate of habituation of subordinate animals was lower than that of both
      socially isolated and dominant animals. The excitability of the LGs following
      habituation was also dependent on social status. Following habituation, the spike
      response of LGs recovered within several minutes; however, they showed
      significant depression with a decrease in excitability. With a 5 or 60 s
      interstimulus interval, subordinate animals showed longer delays of depression
      compared with dominant animals. A decrease in the rate of habituation and a delay
      of depression in subordinate crayfish would be advantageous for maintaining an
      active escape response to evade repeated attacks of dominant animals and a
      reduced learning ability to adapt to social status.

PMID- 23125345
TI  - Implantation reduces the negative effects of bio-logging devices on birds.
AB  - Animal-borne logging or telemetry devices are widely used for measurements of
      physiological and movement data from free-living animals. For such measurements
      to be relevant, however, it is essential that the devices themselves do not
      affect the data of interest. A recent meta-analysis reported an overall negative
      effect of these devices on the birds that bear them, i.e. on nesting
      productivity, clutch size, nest initiation date, offspring quality, body
      condition, flying ability, foraging behaviours, energy expenditure and survival
      rate. Method of attachment (harness, collar, glue, anchor, implant, breast
      mounted or tailmount) had no influence on the strength of these effects but
      anchored and implanted transmitters had the highest reported rates of device
      induced mortality. Furthermore, external devices, but not internal devices,
      caused an increase in 'device-induced behaviour' (comfort behaviours such as
      preening, fluffing and stretching, and unrest activities including unquantifiable
      'active' behaviours). These findings suggest that, with the exception of device
      induced behaviour, external attachment is preferable to implantation. In the
      present study we undertake a meta-analysis of 183 estimates of device impact from
      39 studies of 36 species of bird designed to explicitly compare the effects of
      externally attached and surgically implanted devices on a range of traits,
      including condition, energy expenditure and reproduction. In contrast to a
      previous study, we demonstrate that externally attached devices have a consistent
      detrimental effect (i.e. negative influences on body condition, reproduction,
      metabolism and survival), whereas implanted devices have no consistent effect. We
      also show that the magnitude of the negative effect of externally attached
      devices decreases with time. We therefore conclude that device implantation is
      preferable to external attachment, providing that the risk of mortality
      associated with the anaesthesia and surgery required for implantation can be
      mitigated. We recommend that studies employing external devices use devices that
      can be borne for long periods, and, wherever possible, deploy devices in advance
      of the time period of interest.

PMID- 23125346
TI  - Physiological and agonistic behavioural response of Procambarus clarkii to an
      acoustic stimulus.
AB  - This study examined the effects of an acoustic stimulus on the haemolymph and
      agonistic behaviour of the red swamp crayfish, Procambarus clarkii. The
      experiment was conducted in a tank equipped with a video recording system using
      six groups (three control and three test groups) of five adult crayfish (30
      specimens in total). After 1 h of habituation, the behaviour of the crayfish was
      monitored for 2 h. During the second hour, the animals in the test groups were
      exposed to a linear sweep (frequency range 0.1-25 kHz; peak amplitude 148 dB(rms)
      re. 1 MUPa at 12 kHz) acoustic stimulus for 30 min. Exposure to the noise
      produced significant variations in haemato-immunological parameters as well as a
      reduction in agonistic behaviour.

PMID- 23125347
TI  - Changes in the neural representation of odorants after olfactory deprivation in
      the adult mouse olfactory bulb.
AB  - Olfactory sensory deprivation during development has been shown to induce
      significant alterations in the neurophysiology of olfactory receptor neurons
      (ORNs), the primary sensory inputs to the brain's olfactory bulb. Deprivation has
      also been shown to alter the neurochemistry of the adult olfactory system, but
      the physiological consequences of these changes are poorly understood. Here we
      used in vivo synaptopHluorin (spH) imaging to visualize odorant-evoked
      neurotransmitter release from ORNs in adult transgenic mice that underwent 4
      weeks of unilateral olfactory deprivation. Deprivation reduced odorant-evoked spH
      signals compared with sham-occluded mice. Unexpectedly, this reduction was
      equivalent between ORNs on the open and plugged sides. Changes in odorant
      selectivity of glomerular subpopulations of ORNs were also observed, but only in
      ORNs on the open side of deprived mice. These results suggest that naris
      occlusion in adult mice produces substantial changes in primary olfactory
      processing which may reflect not only the decrease in olfactory stimulation on
      the occluded side but also the alteration of response properties on the intact
      side. We also observed a modest effect of true sham occlusions that included
      noseplug insertion and removal, suggesting that conventional noseplug techniques
      may have physiological effects independent of deprivation per se and thus require
      more careful controls than has been previously appreciated.

PMID- 23125348
TI  - Isolation and characterization of GtMYBP3 and GtMYBP4, orthologues of R2R3-MYB
      transcription factors that regulate early flavonoid biosynthesis, in gentian
      flowers.
AB  - Flavonoids are one of the major plant pigments for flower colour. Not only
      coloured anthocyanins, but also co-pigment flavones or flavonols, accumulate in
      flowers. To study the regulation of early flavonoid biosynthesis, two R2R3-MYB
      transcription factors, GtMYBP3 and GtMYBP4, were identified from the petals of
      Japanese gentian (Gentiana triflora). Phylogenetic analysis showed that these two
      proteins belong to the subgroup 7 clade (flavonol-specific MYB), which includes
      Arabidopsis AtMYB12, grapevine VvMYBF1, and tomato SlMYB12. Gt   MYBP3 and Gt  
      MYBP4 transcripts were detected specifically in young petals and correlated with
      the profiles of flavone accumulation. Transient expression assays showed that
      GtMYBP3 and GtMYBP4 enhanced the promoter activities of early biosynthetic genes,
      including flavone synthase II (FNSII) and flavonoid 3'-hydroxylase (F3'H), but
      not the late biosynthetic gene, flavonoid 3',5'-hydroxylase (F3'5'H). GtMYBP3
      also enhanced the promoter activity of the chalcone synthase (CHS) gene. In
      transgenic Arabidopsis, overexpression of Gt   MYBP3 and Gt   MYBP4 activated the
      expression of endogenous flavonol biosynthesis genes and led to increased
      flavonol accumulation in seedlings. In transgenic tobacco petals, overexpression
      of Gt   MYBP3 and Gt   MYBP4 caused decreased anthocyanin levels, resulting in
      pale flower colours. Gt   MYBP4-expressing transgenic tobacco flowers also showed
      increased flavonols. As far as is known, this is the first functional
      characterization of R2R3-MYB transcription factors regulating early flavonoid
      biosynthesis in petals.

PMID- 23125349
TI  - Normal adaptation of Candida albicans to the murine gastrointestinal tract
      requires Efg1p-dependent regulation of metabolic and host defense genes.
AB  - Although gastrointestinal colonization by the opportunistic fungal pathogen
      Candida albicans is generally benign, severe systemic infections are thought to
      arise due to escape of commensal C. albicans from the gastrointestinal (GI)
      tract. The C. albicans transcription factor Efg1p is a major regulator of GI
      colonization, hyphal morphogenesis, and virulence. The goals of this study were
      to identify the Efg1p regulon during GI tract colonization and to compare C.
      albicans gene expression during colonization of different organs of the GI tract.
      Our results identified significant differences in gene expression between cells
      colonizing the cecum and ileum. During colonization, efg1(-) null mutant cells
      expressed higher levels of genes involved in lipid catabolism, carnitine
      biosynthesis, and carnitine utilization than did colonizing wild-type (WT) cells.
      In addition, during laboratory growth, efg1(-) null mutant cells grew to a higher
      density than WT cells. The efg1(-) null mutant grew in depleted medium, while WT
      cells could grow only if the depleted medium was supplemented with carnitine, a
      compound that promotes the metabolism of fatty acids. Altered gene expression and
      altered growth capability support the ability of efg1(-) cells to hypercolonize
      naive mice. Also, Efg1p was shown to be important for transcriptional responses
      to the stresses present in the cecum environment. For example, during
      colonization, SOD5, encoding a superoxide dismutase, was highly upregulated in an
      Efg1p-dependent manner. Ectopic expression of SOD5 in an efg1(-) null mutant
      increased the fitness of the efg1(-) null mutant cells during colonization. These
      data show that EFG1 is an important regulator of GI colonization.

PMID- 23125350
TI  - White-opaque switching of Candida albicans allows immune evasion in an
      environment-dependent fashion.
AB  - Candida albicans strains that are homozygous at the mating type locus can
      spontaneously and reversibly switch from the normal yeast morphology (white) to
      an elongated cell type (opaque), which is the mating-competent form of the
      fungus. White-opaque switching also influences the ability of C. albicans to
      colonize and proliferate in specific host niches and its susceptibility to host
      defense mechanisms. We used live imaging to observe the interaction of white and
      opaque cells with host phagocytic cells. For this purpose, we generated
      derivatives of the switching-competent strain WO-1 that express green fluorescent
      protein from a white-specific promoter and red fluorescent protein from an opaque
      specific promoter or vice versa. When mixed populations of these differentially
      labeled white and opaque cells were incubated with human polymorphonuclear
      neutrophils (PMNs) on a glass slide, the neutrophils selectively phagocytosed and
      killed white cells, despite frequent physical interaction with opaque cells.
      White cells were attacked only after they started to form a germ tube, indicating
      that the suppression of filamentation in opaque cells saved them from recognition
      by the PMNs. In contrast to neutrophils, dendritic cells internalized white as
      well as opaque cells. However, when embedded in a collagen matrix, the PMNs also
      phagocytosed both white and opaque cells with similar efficiency. These results
      suggest that, depending on the environment, white-opaque switching enables C.
      albicans to escape from specific host defense mechanisms.

PMID- 23125351
TI  - Circadian activation of the mitogen-activated protein kinase MAK-1 facilitates
      rhythms in clock-controlled genes in Neurospora crassa.
AB  - The circadian clock regulates the expression of many genes involved in a wide
      range of biological functions through output pathways such as mitogen-activated
      protein kinase (MAPK) pathways. We demonstrate here that the clock regulates the
      phosphorylation, and thus activation, of the MAPKs MAK-1 and MAK-2 in the
      filamentous fungus Neurospora crassa. In this study, we identified genetic
      targets of the MAK-1 pathway, which is homologous to the cell wall integrity
      pathway in Saccharomyces cerevisiae and the extracellular signal-regulated kinase
      1/2 (ERK1/2) pathway in mammals. When MAK-1 was deleted from Neurospora cells,
      vegetative growth was reduced and the transcript levels for over 500 genes were
      affected, with significant enrichment for genes involved in protein synthesis,
      biogenesis of cellular components, metabolism, energy production, and
      transcription. Additionally, of the ~500 genes affected by the disruption of MAK
      1, more than 25% were previously identified as putative clock-controlled genes.
      We show that MAK-1 is necessary for robust rhythms of two morning-specific genes,
      i.e., ccg-1 and the mitochondrial phosphate carrier protein gene NCU07465.
      Additionally, we show clock regulation of a predicted chitin synthase gene,
      NCU04352, whose rhythmic accumulation is also dependent upon MAK-1. Together,
      these data establish a role for the MAK-1 pathway as an output pathway of the
      circadian clock and suggest a link between rhythmic MAK-1 activity and circadian
      control of cellular growth.

PMID- 23125352
TI  - Role of cytosolic glyceraldehyde-3-phosphate dehydrogenase in visceral organ
      infection by Leishmania donovani.
AB  - The initial 7 steps of the glycolytic pathway from glucose to 3-phosphoglycerate
      are localized in the glycosomes in Leishmania, including step 6, catalyzed by the
      enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In L. donovani and L.
      mexicana, there exists a second GAPDH enzyme present in the cytosol that is
      absent in L. braziliensis and that has become a pseudogene in L. major. To
      investigate the role of the cytosolic GAPDH (cGAPDH), an L. donovani cGAPDH-null
      mutant was generated, and conversely, the functional L. donovani cGAPDH was
      introduced into L. major and the resulting engineered parasites were
      characterized. The L. donovani cGAPDH-null mutant was able to proliferate at the
      same rate as the wild-type parasite in glucose-deficient medium. However, in the
      presence of glucose, the L. donovani cGAPDH-null mutant consumed less glucose and
      proliferated more slowly than the wild-type parasite and displayed reduced
      infectivity in visceral organs of experimentally infected mice. This demonstrates
      that cGAPDH is functional in L. donovani and is required for survival in visceral
      organs. Restoration of cGAPDH activity in L. major, in contrast, had an adverse
      effect on L. major proliferation in glucose-containing medium, providing a
      possible explanation of why it has evolved into a pseudogene in L. major. This
      study indicates that there is a difference in glucose metabolism between L.
      donovani and L. major, and this may represent an important factor in the ability
      of L. donovani to cause visceral disease.

PMID- 23125353
TI  - Dual functions of alpha-ketoglutarate dehydrogenase E2 in the Krebs cycle and
      mitochondrial DNA inheritance in Trypanosoma brucei.
AB  - The dihydrolipoyl succinyltransferase (E2) of the multisubunit alpha
      ketoglutarate dehydrogenase complex (alpha-KD) is an essential Krebs cycle enzyme
      commonly found in the matrices of mitochondria. African trypanosomes
      developmentally regulate mitochondrial carbohydrate metabolism and lack a
      functional Krebs cycle in the bloodstream of mammals. We found that despite the
      absence of a functional alpha-KD, bloodstream form (BF) trypanosomes express
      alpha-KDE2, which localized to the mitochondrial matrix and inner membrane.
      Furthermore, alpha-KDE2 fractionated with the mitochondrial genome, the
      kinetoplast DNA (kDNA), in a complex with the flagellum. A role for alpha-KDE2 in
      kDNA maintenance was revealed in alpha-KDE2 RNA interference (RNAi) knockdowns.
      Following RNAi induction, bloodstream trypanosomes showed pronounced growth
      reduction and often failed to equally distribute kDNA to daughter cells,
      resulting in accumulation of cells devoid of kDNA (dyskinetoplastic) or
      containing two kinetoplasts. Dyskinetoplastic trypanosomes lacked mitochondrial
      membrane potential and contained mitochondria of substantially reduced volume.
      These results indicate that alpha-KDE2 is bifunctional, both as a metabolic
      enzyme and as a mitochondrial inheritance factor necessary for the distribution
      of kDNA networks to daughter cells at cytokinesis.

PMID- 23125354
TI  - Molecular and morphological data support the existence of a sexual cycle in
      species of the genus Paracoccidioides.
AB  - The genus Paracoccidioides includes the thermodimorphic species Paracoccidioides
      brasiliensis and P. lutzii, both of which are etiologic agents of
      paracoccidioidomycosis, a systemic mycosis that affects humans in Latin America.
      Despite the common occurrence of a sexual stage among closely related fungi, this
      has not been observed with Paracoccidioides species, which have thus been
      considered asexual. Molecular evolutionary studies revealed recombination events
      within isolated populations of the genus Paracoccidioides, suggesting the
      possible existence of a sexual cycle. Comparative genomic analysis of all
      dimorphic fungi and Saccharomyces cerevisiae demonstrated the presence of
      conserved genes involved in sexual reproduction, including those encoding mating
      regulators such as MAT, pheromone receptors, pheromone-processing enzymes, and
      mating signaling regulators. The expression of sex-related genes in the yeast and
      mycelial phases of both Paracoccidioides species was also detected by real-time
      PCR, with nearly all of these genes being expressed preferentially in the
      filamentous form of the pathogens. In addition, the expression of sex-related
      genes was responsive to the putative presence of pheromone in the supernatants
      obtained from previous cocultures of strains of two different mating types. In
      vitro crossing of isolates of different mating types, discriminated by
      phylogenetic analysis of the alpha-box (MAT1-1) and the high-mobility-group (HMG)
      domain (MAT1-2), led to the identification of the formation of young ascocarps
      with constricted coiled hyphae related to the initial stage of mating. These
      genomic and morphological analyses strongly support the existence of a sexual
      cycle in species of the genus Paracoccidioides.

PMID- 23125355
TI  - Electromagnetic interference with cardiac pacemakers and implantable cardioverter
      defibrillators from low-frequency electromagnetic fields in vivo.
AB  - AIMS: Electromagnetic interference (EMI) can pose a danger to workers with
      pacemakers and implantable cardioverter-defibrillators (ICDs). At some workplaces
      electromagnetic fields are high enough to potentially inflict EMI. The purpose of
      this in vivo study was to evaluate the susceptibility of pacemakers and ICDs to
      external electromagnetic fields. METHODS AND RESULTS: Eleven volunteers with a
      pacemaker and 13 with an ICD were exposed to sine, pulse, ramp, and square
      waveform magnetic fields with frequencies of 2-200 Hz using Helmholtz coil. The
      magnetic field flux densities varied to 300 uT. We also tested the occurrence of
      EMI from an electronic article surveillance (EAS) gate, an induction cooktop, and
      a metal inert gas (MIG) welding machine. All pacemakers were tested with bipolar
      settings and three of them also with unipolar sensing configurations. None of the
      bipolar pacemakers or ICDs tested experienced interference in any of the exposure
      situations. The three pacemakers with unipolar settings were affected by the
      highest fields of the Helmholtz coil, and one of them also by the EAS gate and
      the welding cable. The induction cooktop did not interfere with any of the
      unipolarly programmed pacemakers. CONCLUSION: Magnetic fields with intensities as
      high as those used in this study are rare even in industrial working
      environments. In most cases, employees can return to work after implantation of a
      bipolar pacemaker or an ICD, after an appropriate risk assessment. Pacemakers
      programmed to unipolar configurations can cause danger to their users in
      environments with high electromagnetic fields, and should be avoided, if
      possible.

PMID- 23125356
TI  - Plant responses to heterogeneous salinity: growth of the halophyte Atriplex
      nummularia is determined by the root-weighted mean salinity of the root zone.
AB  - Soil salinity is generally spatially heterogeneous, but our understanding of
      halophyte physiology under such conditions is limited. The growth and physiology
      of the dicotyledonous halophyte Atriplex nummularia was evaluated in split-root
      experiments to test whether growth is determined by: (i) the lowest; (ii) the
      highest; or (iii) the mean salinity of the root zone. In two experiments, plants
      were grown with uniform salinities or horizontally heterogeneous salinities (10
      450 mM NaCl in the low-salt side and 670 mM in the high-salt side, or 10 mM NaCl
      in the low-salt side and 500-1500 mM in the high-salt side). The combined data
      showed that growth and gas exchange parameters responded most closely to the root
      weighted mean salinity rather than to the lowest, mean, or highest salinity in
      the root zone. In contrast, midday shoot water potentials were determined by the
      lowest salinity in the root zone, consistent with most water being taken from the
      least negative water potential source. With uniform salinity, maximum shoot
      growth was at 120-230 mM NaCl; ~90% of maximum growth occurred at 10 mM and 450
      mM NaCl. Exposure of part of the roots to 1500 mM NaCl resulted in an enhanced
      (+40%) root growth on the low-salt side, which lowered root-weighted mean
      salinity and enabled the maintenance of shoot growth. Atriplex nummularia grew
      even with extreme salinity in part of the roots, as long as the root-weighted
      mean salinity of the root zone was within the 10-450 mM range.

PMID- 23125357
TI  - A combined histology and transcriptome analysis unravels novel questions on
      Medicago truncatula seed coat.
AB  - The seed coat is involved in the determination of seed quality traits such as
      seed size, seed composition, seed permeability, and hormonal regulation.
      Understanding seed coat structure is therefore a prerequisite to deciphering the
      genetic mechanisms that govern seed coat functions. By combining histological and
      transcriptomic data analyses, cellular and molecular events occurring during
      Medicago truncatula seed coat development were dissected in order to relate
      structure to function and pinpoint target genes potentially involved in seed coat
      traits controlling final seed quality traits. The analyses revealed the
      complexity of the seed coat transcriptome, which contains >30 000 genes. In
      parallel, a set of genes showing a preferential expression in seed coat that may
      be involved in more specific functions was identified. The study describes how
      seed coat anatomy and morphological changes affect final seed quality such as
      seed size, seed composition, seed permeability, and hormonal regulation. Putative
      regulator genes of different processes have been identified as potential
      candidates for further functional genomic studies to improve agronomical seed
      traits. The study also raises new questions concerning the implication of seed
      coat endopolyploidy in cell expansion and the participation of the seed coat in
      de novo abscisic acid biosynthesis at early seed filling.

PMID- 23125358
TI  - The secreted purple acid phosphatase isozymes AtPAP12 and AtPAP26 play a pivotal
      role in extracellular phosphate-scavenging by Arabidopsis thaliana.
AB  - Orthophosphate (P(i)) is an essential but limiting macronutrient for plant
      growth. Extensive soil P reserves exist in the form of organic P (P(o)), which is
      unavailable for root uptake until hydrolysed by secretory acid phosphatases
      (APases). The predominant purple APase (PAP) isozymes secreted by roots of P(i)
      deficient (-P(i)) Arabidopsis thaliana were recently identified as AtPAP12
      (At2g27190) and AtPAP26 (At5g34850). The present study demonstrated that
      exogenous P(o) compounds such as glycerol-3-phosphate or herring sperm DNA: (i)
      effectively substituted for P(i) in supporting the P nutrition of Arabidopsis
      seedlings, and (ii) caused upregulation and secretion of AtPAP12 and AtPAP26 into
      the growth medium. When cultivated under -P(i) conditions or supplied with P(o)
      as its sole source of P nutrition, an atpap26/atpap12 T-DNA double insertion
      mutant exhibited impaired growth coupled with >60 and >30% decreases in root
      secretory APase activity and rosette total P(i) concentration, respectively.
      Development of the atpap12/atpap26 mutant was unaffected during growth on P(i)
      replete medium but was completely arrested when 7-day-old P(i)-sufficient
      seedlings were transplanted into a -P(i), P(o)-containing soil mix. Both PAPs
      were also strongly upregulated on root surfaces and in shoot cell-wall extracts
      of -P(i) seedlings. It is hypothesized that secreted AtPAP12 and AtPAP26
      facilitate the acclimation of Arabidopsis to nutritional Pi deficiency by: (i)
      functioning in the rhizosphere to scavenge P(i) from the soil's accessible P(o)
      pool, while (ii) recycling P(i) from endogenous phosphomonoesters that have been
      leaked into cell walls from the cytoplasm. Thus, AtPAP12 and AtPAP26 are
      promising targets for improving crop P-use efficiency.

PMID- 23125359
TI  - Plant sex chromosome evolution.
AB  - It is now well established that plants have an important place in studies of sex
      chromosome evolution because of the repeated independent evolution of separate
      sexes and sex chromosomes. There has been considerable recent progress in
      studying plant sex chromosomes. In this review, I focus on how these recent
      studies have helped clarify or answer several important questions about sex
      chromosome evolution, and I shall also try to clarify some common misconceptions.
      I also outline future work that will be needed to make further progress,
      including testing some important ideas by genetic, molecular, and developmental
      approaches. Systems with different ages can clearly help show the time course of
      events during changes from an ancestral co-sexual state (hermaphroditism or
      monoecy), and I will also explain how different questions can be studied in
      lineages whose dioecy or sex chromosomes evolved at different times in the past.

PMID- 23125360
TI  - Sensitive measurement of single-nucleotide polymorphism-induced changes of RNA
      conformation: application to disease studies.
AB  - Single-nucleotide polymorphisms (SNPs) are often linked to critical phenotypes
      such as diseases or responses to vaccines, medications and environmental factors.
      However, the specific molecular mechanisms by which a causal SNP acts is usually
      not obvious. Changes in RNA secondary structure emerge as a possible explanation
      necessitating the development of methods to measure the impact of single
      nucleotide variation on RNA structure. Despite the recognition of the importance
      of considering the changes in Boltzmann ensemble of RNA conformers in this
      context, a formal method to perform directly such comparison was lacking. Here,
      we solved this problem and designed an efficient method to compute the relative
      entropy between the Boltzmann ensembles of the native and a mutant structure. On
      the basis of this theoretical progress, we developed a software tool, remuRNA,
      and investigated examples of its application. Comparing the impact of common SNPs
      naturally occurring in populations with the impact of random point mutations, we
      found that structural changes introduced by common SNPs are smaller than those
      introduced by random point mutations. This suggests a natural selection against
      mutations that significantly change RNA structure and demonstrates, surprisingly,
      that randomly inserted point mutations provide inadequate estimation of random
      mutations effects. Subsequently, we applied remuRNA to determine which of the
      disease-associated non-coding SNPs are potentially related to RNA structural
      changes.

PMID- 23125361
TI  - The mammalian TRIM-NHL protein TRIM71/LIN-41 is a repressor of mRNA function.
AB  - TRIM-NHL proteins are conserved regulators of development and differentiation but
      their molecular function has remained largely elusive. Here, we report an as yet
      unrecognized activity for the mammalian TRIM-NHL protein TRIM71 as a repressor of
      mRNAs. We show that TRIM71 is associated with mRNAs and that it promotes
      translational repression and mRNA decay. We have identified Rbl1 and Rbl2, two
      transcription factors whose down-regulation is important for stem cell function,
      as TRIM71 targets in mouse embryonic stem cells. Furthermore, one of the defining
      features of TRIM-NHL proteins, the NHL domain, is necessary and sufficient to
      target TRIM71 to RNA, while the RING domain that confers ubiquitin ligase
      activity is dispensable for repression. Our results reveal strong similarities
      between TRIM71 and Drosophila BRAT, the best-studied TRIM-NHL protein and a well
      documented translational repressor, suggesting that BRAT and TRIM71 are part of a
      family of mRNA repressors regulating proliferation and differentiation.

PMID- 23125362
TI  - Rfam 11.0: 10 years of RNA families.
AB  - The Rfam database (available via the website at http://rfam.sanger.ac.uk and
      through our mirror at http://rfam.janelia.org) is a collection of non-coding RNA
      families, primarily RNAs with a conserved RNA secondary structure, including both
      RNA genes and mRNA cis-regulatory elements. Each family is represented by a
      multiple sequence alignment, predicted secondary structure and covariance model.
      Here we discuss updates to the database in the latest release, Rfam 11.0,
      including the introduction of genome-based alignments for large families, the
      introduction of the Rfam Biomart as well as other user interface improvements.
      Rfam is available under the Creative Commons Zero license.

PMID- 23125363
TI  - A co-localization model of paired ChIP-seq data using a large ENCODE data set
      enables comparison of multiple samples.
AB  - Deep sequencing approaches, such as chromatin immunoprecipitation by sequencing
      (ChIP-seq), have been successful in detecting transcription factor-binding sites
      and histone modification in the whole genome. An approach for comparing two
      different ChIP-seq data would be beneficial for predicting unknown functions of a
      factor. We propose a model to represent co-localization of two different ChIP-seq
      data. We showed that a meaningful overlapping signal and a meaningless background
      signal can be separated by this model. We applied this model to compare ChIP-seq
      data of RNA polymerase II C-terminal domain (CTD) serine 2 phosphorylation with a
      large amount of peak-called data, including ChIP-seq and other deep sequencing
      data in the Encyclopedia of DNA Elements (ENCODE) project, and then extracted
      factors that were related to RNA polymerase II CTD serine 2 in HeLa cells. We
      further analyzed RNA polymerase II CTD serine 7 phosphorylation, of which their
      function is still unclear in HeLa cells. Our results were characterized by the
      similarity of localization for transcription factor/histone modification in the
      ENCODE data set, and this suggests that our model is appropriate for
      understanding ChIP-seq data for factors where their function is unknown.

PMID- 23125364
TI  - Global analysis of mRNA stability in Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis (MTB) is a highly successful pathogen that infects
      over a billion people. As with most organisms, MTB adapts to stress by modifying
      its transcriptional profile. Remodeling of the transcriptome requires both
      altering the transcription rate and clearing away the existing mRNA through
      degradation, a process that can be directly regulated in response to stress. To
      understand better how MTB adapts to the harsh environs of the human host, we
      performed a global survey of the decay rates of MTB mRNA transcripts. Decay rates
      were measured for 2139 of the ~4000 MTB genes, which displayed an average half
      life of 9.5 min. This is nearly twice the average mRNA half-life of other
      prokaryotic organisms where these measurements have been made. The transcriptome
      was further stabilized in response to lowered temperature and hypoxic stress. The
      generally stable transcriptome described here, and the additional stabilization
      in response to physiologically relevant stresses, has far-ranging implications
      for how this pathogen is able to adapt in its human host.

PMID- 23125365
TI  - HBVdb: a knowledge database for Hepatitis B Virus.
AB  - We have developed a specialized database, HBVdb (http://hbvdb.ibcp.fr), allowing
      the researchers to investigate the genetic variability of Hepatitis B Virus (HBV)
      and viral resistance to treatment. HBV is a major health problem worldwide with
      more than 350 million individuals being chronically infected. HBV is an enveloped
      DNA virus that replicates by reverse transcription of an RNA intermediate. HBV
      genome is optimized, being circular and encoding four overlapping reading frames.
      Indeed, each nucleotide of the genome takes part in the coding of at least one
      protein. However, HBV shows some genome variability leading to at least eight
      different genotypes and recombinant forms. The main drugs used to treat infected
      patients are nucleos(t)ides analogs (reverse transcriptase inhibitors).
      Unfortunately, HBV mutants resistant to these drugs may be selected and be
      responsible for treatment failure. HBVdb contains a collection of computer
      annotated sequences based on manually annotated reference genomes. The database
      can be accessed through a web interface that allows static and dynamic queries
      and offers integrated generic sequence analysis tools and specialized analysis
      tools (e.g. annotation, genotyping, drug resistance profiling).

PMID- 23125366
TI  - Xenbase: expansion and updates of the Xenopus model organism database.
AB  - Xenbase (http://www.xenbase.org) is a model organism database that provides
      genomic, molecular, cellular and developmental biology content to biomedical
      researchers working with the frog, Xenopus and Xenopus data to workers using
      other model organisms. As an amphibian Xenopus serves as a useful evolutionary
      bridge between invertebrates and more complex vertebrates such as birds and
      mammals. Xenbase content is collated from a variety of external sources using
      automated and semi-automated pipelines then processed via a combination of
      automated and manual annotation. A link-matching system allows for the wide
      variety of synonyms used to describe biological data on unique features, such as
      a gene or an anatomical entity, to be used by the database in an equivalent
      manner. Recent updates to the database include the Xenopus laevis genome, a new
      Xenopus tropicalis genome build, epigenomic data, collections of RNA and protein
      sequences associated with genes, more powerful gene expression searches, a
      community and curated wiki, an extensive set of manually annotated gene
      expression patterns and a new database module that contains data on over 700
      antibodies that are useful for exploring Xenopus cell and developmental biology.

PMID- 23125367
TI  - Natural zinc ribbon HNH endonucleases and engineered zinc finger nicking
      endonuclease.
AB  - Many bacteriophage and prophage genomes encode an HNH endonuclease (HNHE) next to
      their cohesive end site and terminase genes. The HNH catalytic domain contains
      the conserved catalytic residues His-Asn-His and a zinc-binding site [CxxC](2).
      An additional zinc ribbon (ZR) domain with one to two zinc-binding sites
      ([CxxxxC], [CxxxxH], [CxxxC], [HxxxH], [CxxC] or [CxxH]) is frequently found at
      the N-terminus or C-terminus of the HNHE or a ZR domain protein (ZRP) located
      adjacent to the HNHE. We expressed and purified 10 such HNHEs and characterized
      their cleavage sites. These HNHEs are site-specific and strand-specific nicking
      endonucleases (NEase or nickase) with 3- to 7-bp specificities. A minimal HNH
      nicking domain of 76 amino acid residues was identified from Bacillus phage gamma
      HNHE and subsequently fused to a zinc finger protein to generate a chimeric NEase
      with a new specificity (12-13 bp). The identification of a large pool of
      previously unknown natural NEases and engineered NEases provides more 'tools' for
      DNA manipulation and molecular diagnostics. The small modular HNH nicking domain
      can be used to generate rare NEases applicable to targeted genome editing. In
      addition, the engineered ZF nickase is useful for evaluation of off-target sites
      in vitro before performing cell-based gene modification.

PMID- 23125368
TI  - Identification of one of the apurinic/apyrimidinic lyase active sites of
      topoisomerase V by structural and functional studies.
AB  - Topoisomerase V (Topo-V) is the only member of a novel topoisomerase subtype.
      Topo-V is unique because it is a bifunctional enzyme carrying both topoisomerase
      and DNA repair lyase activities within the same protein. Previous studies had
      shown that the topoisomerase domain spans the N-terminus of the protein and is
      followed by 12 tandem helix-hairpin-helix [(HhH)(2)] domains. There are at least
      two DNA repair lyase active sites for apurinic/apyrimidinic (AP) site processing,
      one within the N-terminal region and the second within the C-terminal domain of
      Topo-V, but their exact locations and characteristics are unknown. In the present
      study, the N-terminal 78-kDa fragment of Topo-V (Topo-78), containing the
      topoisomerase domain and one of the lyase DNA repair domains, was characterized
      by structural and biochemical studies. The results show that an N-terminal 69-kDa
      fragment is the minimal fragment with both topoisomerase and AP lyase activities.
      The lyase active site of Topo-78 is at the junction of the fifth and sixth
      (HhH)(2) domains. From the biochemical and structural data, it appears that
      Lys571 is the most probable nucleophile responsible for the lyase activity. Our
      experiments also suggest that Topo-V most likely acts as a Class I AP
      endonuclease in vivo.

PMID- 23125369
TI  - Telomerase-dependent generation of 70-nt-long telomeric single-stranded 3'
      overhangs in yeast.
AB  - Telomeres, the chromatin structures at the ends of eukaryotic chromosomes, are
      essential for chromosome stability. The telomere terminates with a TG-rich 3'
      overhang, which is bound by sequence-specific proteins that both protect the end
      and regulate the telomerase elongation process. Here, we demonstrate the presence
      of 3' overhangs as long as 200 nt in asynchronously growing cells of the budding
      yeast Saccharomyces castellii. The 3' overhangs show a wide distribution of 14
      200 nt in length, thus resembling the distribution found in human cells. A
      substantially large fraction of the 3' overhangs resides in the 70-200 nt range.
      Remarkably, we found an accumulation of a distinct class of 70-nt-long 3'
      overhangs in the S phase of the cell cycle. Cells without a functional telomerase
      showed the same wide distribution of 3' overhangs, but significantly, lacked the
      specific fraction of 70-nt 3' overhangs. Hence, our data show that the highly
      defined 70-nt 3' overhangs are generated by a telomerase-dependent mechanism,
      which is uncoupled to the mechanisms producing the bulk of the 3' overhangs.
      These data provide new insights that will be helpful for deciphering the complex
      interplay between the specialized telomere replication machinery and the
      conventional DNA replication.

PMID- 23125370
TI  - MiR-210 disturbs mitotic progression through regulating a group of mitosis
      related genes.
AB  - MiR-210 is up-regulated in multiple cancer types but its function is disputable
      and further investigation is necessary. Using a bioinformatics approach, we
      identified the putative target genes of miR-210 in hypoxia-induced CNE cells from
      genome-wide scale. Two functional gene groups related to cell cycle and RNA
      processing were recognized as the major targets of miR-210. Here, we investigated
      the molecular mechanism and biological consequence of miR-210 in cell cycle
      regulation, particularly mitosis. Hypoxia-induced up-regulation of miR-210 was
      highly correlated with the down-regulation of a group of mitosis-related genes,
      including Plk1, Cdc25B, Cyclin F, Bub1B and Fam83D. MiR-210 suppressed the
      expression of these genes by directly targeting their 3'-UTRs. Over-expression of
      exogenous miR-210 disturbed mitotic progression and caused aberrant mitosis.
      Furthermore, miR-210 mimic with pharmacological doses reduced tumor formation in
      a mouse metastatic tumor model. Taken together, these results implicate that miR
      210 disturbs mitosis through targeting multi-genes involved in mitotic
      progression, which may contribute to its inhibitory role on tumor formation.

PMID- 23125371
TI  - FlyBase: improvements to the bibliography.
AB  - An accurate, comprehensive, non-redundant and up-to-date bibliography is a
      crucial component of any Model Organism Database (MOD). Principally, the
      bibliography provides a set of references that are specific to the field served
      by the MOD. Moreover, it serves as a backbone to which all curated biological
      data can be attributed. Here, we describe the organization and main features of
      the bibliography in FlyBase (flybase.org), the MOD for Drosophila melanogaster.
      We present an overview of the current content of the bibliography, the pipeline
      for identifying and adding new references, the presentation of data within
      Reference Reports and effective methods for searching and retrieving
      bibliographic data. We highlight recent improvements in these areas and describe
      the advantages of using the FlyBase bibliography over alternative literature
      resources. Although this article is focused on bibliographic data, many of the
      features and tools described are applicable to browsing and querying other
      datasets in FlyBase.

PMID- 23125372
TI  - Non-B DB v2.0: a database of predicted non-B DNA-forming motifs and its
      associated tools.
AB  - The non-B DB, available at http://nonb.abcc.ncifcrf.gov, catalogs predicted non-B
      DNA-forming sequence motifs, including Z-DNA, G-quadruplex, A-phased repeats,
      inverted repeats, mirror repeats, direct repeats and their corresponding subsets:
      cruciforms, triplexes and slipped structures, in several genomes. Version 2.0 of
      the database revises and re-implements the motif discovery algorithms to better
      align with accepted definitions and thresholds for motifs, expands the non-B DNA
      forming motifs coverage by including short tandem repeats and adds key
      visualization tools to compare motif locations relative to other genomic
      annotations. Non-B DB v2.0 extends the ability for comparative genomics by
      including re-annotation of the five organisms reported in non-B DB v1.0, human,
      chimpanzee, dog, macaque and mouse, and adds seven additional organisms:
      orangutan, rat, cow, pig, horse, platypus and Arabidopsis thaliana. Additionally,
      the non-B DB v2.0 provides an overall improved graphical user interface and
      faster query performance.

PMID- 23125373
TI  - Iodinated contrast injection data from a new technology.
AB  - PURPOSE: To introduce a new power injection technology that generates data as a
      digital imaging and communications in medicine (DICOM) image linked to individual
      patient imaging studies. In addition, to determine the fraction of patients in a
      subject cohort whose contrast injection data was captured as a DICOM image and to
      analyze contrast injection properties for those patients. METHODS: Over a 1-month
      period, authors performed a retrospective evaluation of 242 patients' consecutive
      contrast-enhanced computed tomography (CT) studies from a single 320-detector CT
      scanner in an academic radiology department. Authors gathered unique patient and
      examination identifiers, prescribed and injected contrast and saline volumes,
      prescribed and injected flow rate, and mean and maximum injection pressures. The
      literature was reviewed for the initial description of power injectors in
      radiology. RESULTS: Of the 242 CT studies evaluated, 98% had contrast injection
      data amended to the radiology images. For all patients, the mean volume of
      residual contrast was 5 mL. The differences between the prescribed and actual
      flow rate were small. Three patients reached the maximum pressure of 300 psi.
      There were no contrast extravasations. Discussion The most clinically relevant
      finding was that the injector and software system generated a detailed report of
      contrast administration. In 98% of the cases, this report was incorporated into
      the patient's permanent medical record and was available to the radiologist via a
      single DICOM image. CONCLUSION: Contrast injection data can be captured in DICOM
      format and reliably attached to a clinical contrast-enhanced CT image set for
      radiologist use.

PMID- 23125374
TI  - Degree Requirement.

PMID- 23125377
TI  - Kudos.

PMID- 23125378
TI  - How cultural competency can help reduce health disparities.
AB  - Radiologic technologists encounter patients from a variety of racial, ethnic, and
      socioeconomic backgrounds. Reduced income and access to health care among
      minority and immigrant populations accounts for many health disparities.
      Enhancing cultural competency among health care providers and providing
      culturally appropriate services can improve communication, access to health care,
      and eventually health outcomes. Although awareness of a patient's ethnic or
      racial background can aid in screening and diagnosis, patient-centered care
      requires that everyone be seen as individuals first and members of a racial or
      ethnic minority second.

PMID- 23125379
TI  - Pediatric bone densitometry.
AB  - Discussions regarding bone density typically focus on postmenopausal women,
      osteoporosis, and fracture risk. Although these are the most common reasons
      patients have skeletal strength assessments, the use of bone densitometry and
      bone mineral density measurement in pediatric patients is becoming increasingly
      valuable to assess children with diseases that cause inadequate bone growth. This
      article discusses pediatric bone disease and current and emerging imaging options
      for assessing bone density in children and adolescents.

PMID- 23125380
TI  - Diagnosing an ectopic pregnancy with ultrasound imaging.

PMID- 23125381
TI  - A consumer health overview for imaging professionals.

PMID- 23125385
TI  - Survey research.

PMID- 23125386
TI  - Saving lecture from the dustbin.

PMID- 23125387
TI  - What is the big deal about student supervision?

PMID- 23125388
TI  - UpRight: a radiographic marker that displays upright angle on portable chest and
      abdominal radiographs.

PMID- 23125389
TI  - Foundations of CT: the radon problem.

PMID- 23125390
TI  - Emergency situation.

PMID- 23125391
TI  - Plasma fibrinogen is an accurate marker of disease activity in patients with
      polymyalgia rheumatica.
AB  - OBJECTIVE: The overall aim of this study was to establish whether plasma
      fibrinogen was a superior biomarker of disease activity in active PMR than the
      standard biomarkers, ESR and CRP. METHODS: Sixty patients with PMR were divided
      into active (n = 25) or inactive (n = 35) disease groups based on symptoms,
      physician assessment and biomarkers ESR and CRP. Plasma fibrinogen was assayed.
      Groups underwent assessment at baseline and 6 weeks. Disease activity as per the
      PMR activity score (PMR-AS) was recorded at all visits. Receiver operator curves
      (ROCs), predictive values and likelihood ratios were calculated for all
      biomarkers. RESULTS: Disease activity measures improved significantly in the
      active group between weeks 1 and 6 (P < 0.001). There was no significant
      difference between the activity scores at week 6 in the active group and the
      inactive group. Mean fibrinogen decreased from 5.2 to 3.5 g/l (normal <4 g/l)
      between weeks 1 and 6 in the active group. Mean ESR and CRP decreased from 59.6
      to 24.3 mm/h (normal <30 mm/h) and 45.9 to 12.66 mg/l (normal <5 mg/l),
      respectively. Receiver operator curve analysis revealed fibrinogen to be more
      specific than either ESR or CRP for the detection of response to treatment in
      active PMR, with an overall sensitivity and specificity of 92% and 96%,
      respectively. Values above the upper limit of normal for fibrinogen, CRP and ESR
      were associated with likelihood ratios for active disease of 20.53, 2.9 and 2.8,
      respectively (P < 0.001). CONCLUSION: Plasma fibrinogen is at least as useful as
      CRP and ESR for the diagnosis of active PMR and more specific for confirmation of
      response to treatment than either ESR or CRP.

PMID- 23125392
TI  - Non-invasive vascular imaging in perforator flap surgery.
AB  - Preoperative imaging using a range of imaging modalities has become increasingly
      popular for preoperative planning in plastic surgery, in particular in perforator
      flap surgery. Modalities in this role include ultrasound (US), magnetic resonance
      angiography (MRA), and computed tomographic angiography (CTA). The evidence for
      the use of these techniques has been reported in only a handful of studies. In
      this paper we conducted a non-systematic review of the literature to establish
      the role for each of these modalities. The role of state-of-the-art vascular
      imaging as an application in perforator flap surgery is thus offered.

PMID- 23125393
TI  - Uncommon gastrointestinal complications after liver transplantation: radiologic
      findings and clinical features.
AB  - There are various uncommon gastrointestinal complications, as liver
      transplantation becomes increasingly popular as the only curative method for
      patients with end-stage liver diseases. It is important for radiologists
      evaluating postoperative liver transplantation recipients to have a perspective
      on the possible gastrointestinal complications after liver transplantation and
      their radiologic features for early detection and early treatment. This article
      illustrates radiologic findings and clinical features of various uncommon
      gastrointestinal complications after liver transplantation.

PMID- 23125394
TI  - Three-dimensional Look-Locker MRI for evaluation of postcontrast myocardial and
      blood T1 values: comparison with two-dimensional Look-Locker and late gadolinium
      enhancement MRI.
AB  - BACKGROUND: Two-dimensional (2D) Look-Locker MRI technique can identify
      myocardial fibrosis, but cannot cover the whole left ventricle during a single
      scan. PURPOSE: To develop breath-hold three-dimensional (3D) Look-Locker MRI for
      the evaluation of postcontrast myocardial and blood T1 values and myocardial
      scarring in the left ventricle. MATERIAL AND METHODS: A phantom and 24 patients
      with myocardial diseases underwent gadolinium-enhanced 2D and 3D Look-Locker MRI
      using a 1.5-T unit. We compared the T1 value of the phantom and the values of the
      myocardium and blood in the patients between the two Look-Locker MRI sequences.
      In the patient study, the scan ordering of the two Look-Locker MRI was selected
      randomly. We also assessed the ability of the 3D imaging to detect myocardial
      scarring that was confirmed by late gadolinium enhancement MRI. RESULTS: The
      phantom study showed a good agreement for the T1 value between 2D and 3D Look
      Locker MRI. There were no significant differences in the myocardial T1 values
      after contrast between 2D and 3D Look-Locker MRI or in the T1 values between the
      two imaging slices on the 3D Look-Locker MRI (P > 0.10). A better agreement for
      the myocardial T1 values was found when the 3D Look-Locker imaging was performed
      first. The T1 values for blood were affected by the scan order (P < 0.05). The 3D
      Look-Locker MRI showed myocardial scarring with a shorter T1 value (290.4 +/-
      62.7 ms) than those for unscarred myocardium (360.8 +/- 30.3 ms). CONCLUSION:
      Three-dimensional Look-Locker MRI may precisely estimate the postcontrast
      myocardial and blood T1 values for the entire left ventricle during a single
      scan.

PMID- 23125395
TI  - Prevalence of thyroid dysfunction and effect of contrast medium on thyroid
      metabolism in cardiac patients undergoing coronary angiography.
AB  - BACKGROUND: Iodinated contrast media (CM) may influence thyroid function.
      Precautions are generally taken in patients with hyperthyroidism, even if
      subclinical, whereas the risks in patients with hypothyroidism or low
      triiodothyronine (T3) syndrome are not considered as appreciable. PURPOSE: To
      assess the presence and type of thyroid dysfunction in patients admitted for
      coronary angiography (CA), to assess the concentration of free-iodide in five non
      ionic CM, and to evaluate changes in thyroid function after CA in patients with
      low T3 syndrome. MATERIAL AND METHODS: We measured free T3, free thyroxine (T4),
      and thyroid-stimulating hormone (TSH) in 1752 consecutive patients prior to CA
      and free-iodide in five non-ionic CM. Urinary free-iodide before and 24 h after
      CA, and thyroid hormone profile 48 h after CA were also made in 17 patients with
      low T3 syndrome. Patients were followed up for an average duration of 63.5
      months. RESULTS: The patients were divided into four groups: euthyroidism (60%),
      low T3 syndrome (28%), hypothyroidism (10%), and hyperthyroidism (2%). The free
      iodide resulted far below the recommended limit of 50 ug/mL in all tested CM. In
      low T3 syndrome, 24-h free-iodide increased after CA from 99.9 +/- 63 ug to 12276
      +/- 9285 ug (P < 0.0001). A reduction in TSH (4.97 +/- 1.1 vs. 4.17 +/- 1.1
      mUI/mL, P < 0.01) and free T3 (1.44 +/- 0.2 vs. 1.25 +/- 0.3 pg/mL, P < 0.01),
      with an increase in free T4 (11.3 +/- 2.9 vs. 12.5 +/- 3.4 pg/dL, P < 0.001), was
      found. Patients with functional thyroid disease in the follow-up had a
      significant lower rate survival compared to euthyroid patients (90.7 vs. 82.2%, P
      < 0.00001). CONCLUSION: Thyroid dysfunction is frequent in patients who perform a
      CA, and low T3 syndrome is the predominant feature. The administration of
      contrast medium may further compromise the thyroid function.

PMID- 23125396
TI  - Improving social cognition in schizophrenia: a pilot intervention combining
      computerized social cognition training with cognitive remediation.
AB  - BACKGROUND: Social cognition is significantly impaired in schizophrenia and
      contributes to poor community functioning. This study examined whether cognitive
      remediation (CR; COGPACK), shown to improve neurocognition, improves an integral
      component of social cognition, emotion perception, compared with CR combined with
      a computerized Emotion Perception intervention (Mind Reading: Interactive Guide
      to Emotions [MRIGE]). METHODS: 59 stable schizophrenia or schizoaffective
      predominantly inpatients were randomized to either CR (N=27) alone or CR+MRIGE
      (N=32) for 12 weeks. Assessments included the Facial Emotion Identification Task
      (FEIT), Facial Emotion Discrimination Task (FEDT), MCCB-MATRICS, Personal and
      Social Performance Scale, and the Positive and Negative Syndrome Scale. RESULTS:
      There was a significant group-by-time effect on FEIT (F=11.509, P=.004); CR+MRIGE
      demonstrated significantly greater improvement than CR alone (CR+MRIGE, Z=1.89,
      P=.05; CR alone Z=0.57, P=.13). There was significant group-by-time effect on
      FEDT (F=5.663, P=.022); CR+MRIGE demonstrated significantly greater improvement
      than CR alone (CR+MRIGE, Z=1.90, P=.05; CR alone Z=0.67, P=.21). There was also a
      significant group by time effect for social cognition, measured by the Mayer
      Salovey-Caruso Emotional Intelligence Test (F=5.473, P=.050): CR+MRIGE
      demonstrated significantly greater improvement than CR alone (CR+MRIGE, Z=1.98,
      P=.02; CR alone, Z=1.00, P=.05). CONCLUSIONS: Combined CR with emotion perception
      remediation produced greater improvements in emotion recognition, emotion
      discrimination, social functioning, and neurocognition compared with CR alone in
      chronic schizophrenia.

PMID- 23125397
TI  - Disentangling consumer and provider predictors of advance care planning.
AB  - Factorial surveys were used to examine community-based long-term care providers'
      judgments about consumers' need for advance care planning (ACP) and comfort
      levels in discussing ACP. Providers (448 registered nurses and social workers)
      judged vignettes based on hypothetical consumers. Hierarchical linear models
      indicated providers judged consumers who were older, had end-stage diagnoses,
      multiple emergency department visits, and uninvolved caregivers as most in need
      of ACP. These variables explained 10% of the variance in judgments. Providers'
      beliefs about ACP predicted judgments of need for ACP and comfort level in
      discussing ACP. Provider characteristics explained more variance in comfort
      levels (44%) than in judgments of need (20%). This study demonstrates the need
      for tailored educational programs to increase comfort levels and address ACP
      misconceptions. 

PMID- 23125398
TI  - Physician attitudes toward advanced directives: a literature review of variables
      impacting on physicians attitude toward advance directives.
AB  - PURPOSE: To review physician's attitudes as well as the variables that may impact
      on physicians' attitude toward advance directives (ADs). METHOD: Literature
      review of 17 published articles, covering the period 1989 to 2011. FINDINGS:
      Physicians overall have a positive attitude toward patients' AD. However, other
      factors affect this "general positive attitude." These factors influence the
      attitude-behavior relationship of physicians, and hence their actual practice in
      relation to patients' AD. CONCLUSION: The findings from this review are of
      importance in explaining the differences in the attitude of physicians toward AD
      and their compliance. This raises the issue of consideration of other ethical
      paradigms/theories in the clinical context other than the framework of
      "principlism-"based autonomy, on which AD leans on. This is important in light of
      the pluralism of ethical theories.

PMID- 23125399
TI  - Pharmacotherapy of obsessive-compulsive disorder: evidence-based treatment and
      beyond.
AB  - BACKGROUND: Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder
      associated with a significant degree of functional disability and poor quality of
      life. Pharmacotherapy may have a substantial impact on the course and outcome of
      OCD. METHOD: We review the evidence supporting available strategies for the
      pharmacological treatment of OCD. RESULTS: Selective serotonin reuptake
      inhibitors (SSRIs) remain the pharmacological treatment of choice and are
      associated with improved health-related quality of life. Discontinuation is
      associated with relapse and loss of quality of life, implying treatment should
      continue long-term. A substantial minority of patients who fail to respond to
      SSRI may benefit from dose elevation or adjunctive antipsychotics, though long
      term trials validating the effectiveness and tolerability of these strategies are
      relatively lacking. CONCLUSION: The pharmacological evidence-base for the
      treatment of OCD is becoming increasingly robust. Treatment with SSRIs and
      clomipramine remains uncontroversial and improvements are sustained over time.
      Newer compounds targeting serotonin receptor subtypes and other neurotransmitter
      systems are undergoing evaluation.

PMID- 23125400
TI  - Out of the darkness: the impact of a mood disorder over time.
AB  - OBJECTIVE: Being diagnosed with depression or bipolar disorder has a significant
      impact on an individual's life. This paper reports data examining how patients
      view having had such a condition. METHOD: Patients attending the Black Dog
      Institute Depression Clinic were asked to complete questionnaires examining the
      impact of being diagnosed with a mood disorder and dealing with that condition
      over time. RESULTS: Patient responses were analysed qualitatively (in terms of
      positive, negative and neutral responses) and their quantitative distribution was
      examined. Themes were relatively consistent across unipolar and bipolar patients.
      Negative themes included family and work consequences, social impairment and a
      loss of self-confidence. Positive themes included the development of stronger
      familial bonds, the provision of relief and hope, positive treatment outcomes and
      the explanatory benefits of receiving a diagnosis. CONCLUSIONS: Findings indicate
      quite contrasting courses reported by patients with mood disorders (irrespective
      of polarity), ranging from negative to very positive evaluations.

PMID- 23125401
TI  - Risk perception of obesity and bariatric surgery in patients seeking treatment
      for obesity.
AB  - Bariatric surgery (BSx) produces clinically relevant weight loss that translates
      into improved quality of life, decreased mortality, and reduction in medical
      comorbidities, including cardiovascular (CV) risk. Little is known about
      patients' decision-making process to undergo BSx, but risk perception is known to
      influence medical decision-making. This study examined CV and BSx risk perception
      in obese subjects undergoing BSx (n = 268) versus those managed medically (MM) (n
      = 273). This retrospective population-based survey of subjects evaluated for BSx
      had 148 (55%) and 88 (32%) responders in the BSx and MM groups, respectively.
      Survey questions assessed risk perceptions and habits prior to weight loss
      intervention. CV risk was calculated using the Framingham Risk Score (FRS). At
      baseline, BSx subjects had a greater body mass index and greater prevalence of
      diabetes and depression. Follow-up mean weight loss was greater in the BSx group.
      BSx subjects perceived obesity as a greater risk to their overall health than the
      surgical risk. FRS declined in the BSx group (10 to 5%; p < 0.001) while there
      was no change in the MM group (8 to 8%; p = 0.54). Those without a measurable
      decrease in CV risk had a greater tendency to perceive the risk of BSx as greater
      than that of obesity. Obese subjects undergoing BSx are more likely than MM
      subjects to perceive obesity as a greater risk to their health than BSx. MM
      subjects generally underestimate their CV risk and overestimate the risk of BSx.
      Active discussion of CV risk using the FRS and the perception of risk associated
      with bariatric surgery can enhance patients' ability to make an informed decision
      regarding their management. 

PMID- 23125402
TI  - Association of risk factors with acute myocardial infarction in Middle Eastern
      countries: the INTERHEART Middle East study.
AB  - BACKGROUND AND OBJECTIVES: Mortality from cardiovascular disease in the Middle
      East (ME) is projected to increase substantially by 2020. There are no large
      studies on the impact of risk factors for acute myocardial infarction (AMI) in
      the region. This is a report on the association of nine risk factors with AMI in
      the ME. METHODS AND RESULTS: As part of the INTERHEART (IH) study, we enrolled
      1364 cases of first AMI and 1525 matching controls from eight ME countries. The
      age at first AMI was 51.2 +/- 10.3 years, which is the youngest, and with the
      largest proportion of patients <40 years in the entire IH population. The overall
      population attributable risk (PAR) of the nine risk factors to AMI was higher in
      the ME (97.5%) than worldwide (90.4%). Elevated apolipoprotein (Apo)B/ApoA1 had
      the strongest association with AMI, with odds ratio (OR) of 3.43 and PAR of
      57.1%, followed by smoking (OR 3.63 and PAR 45.6%). ApoB/ApoA1 had greater
      association than the conventional low-density lipoprotein (LDL)/high-density
      lipoprotein (HDL) cholesterol ratio. Both diabetes (OR 3.42, PAR 16.4%) and
      hypertension (OR 1.89, PAR 10.7%) had greater association with AMI in women than
      men. Abdominal obesity (OR 2.12, PAR 26.1%) and depression (OR 1.97, PAR 45.3%),
      but not conventional BMI, were significantly associated with AMI (p < 0.0001).
      CONCLUSION: This is the largest prospective population study of risk factors
      associated with AMI in the ME. AMI occurs at younger age in the ME than all other
      regions. The PAR for the nine risk factors was higher in the ME (97.5%) than the
      rest of the world. These findings should guide serious prevention strategies.

PMID- 23125404
TI  - Genetic variation and structure within 3 endangered Calanthe species
      (Orchidaceae) from Korea: inference of population-establishment history and
      implications for conservation.
AB  - It is thought that the warm-temperate vegetation of Korea, which at present is
      limited to southern coastal areas, was founded by individuals from glacial
      refugia putatively located in southern Japan and/or southern China. Two scenarios
      of postglacial recolonization can be hypothesized: 1) extant Korean populations
      are derived from multiple source populations or, 2) they originated from a single
      source. To test which of these scenarios is more likely, we surveyed patterns of
      genetic diversity in 3 congeneric terrestrial orchids that are typical of Korean
      warm-temperate vegetation, Calanthe discolor, C. sieboldii, and C. reflexa. In
      total, we studied 14 populations with 17 allozyme loci. To complement the study,
      we also tested the 2 scenarios with previous population-genetics data reported
      for other warm-temperate plant species native to Korea. Levels of genetic
      variation in the 3 Calanthe species were substantially higher than those typical
      of allozyme-based studies in other terrestrial orchid species, which clearly
      suggest a pattern of postglacial recolonization fitting the first scenario.
      However, previous studies with native Korean species showed equivocal patterns
      and suggest conflicting scenarios. The Calanthe species studied here and the
      previous genetic surveys conducted on other species indicate that the
      establishment of contemporary warm-temperate vegetation in Korea has been diverse
      since deglaciation. From a conservation perspective, C. reflexa should be
      regarded as endangered in Korea, needing special attention to preserve its
      current genetic diversity and to prevent further decreases in population sizes.

PMID- 23125405
TI  - Evaluating the performance of captive breeding techniques for conservation
      hatcheries: a case study of the delta smelt captive breeding program.
AB  - The delta smelt, an endangered fish species endemic to the San Francisco Bay
      Delta, California, United States, was recently brought into captivity for species
      preservation. This study retrospectively evaluates the implementation of a
      genetic management plan for the captive delta smelt population. The captive
      genetic management plan entails tagging fish, molecular data collection, pedigree
      reconstruction, relatedness estimation, and recommending fish crosses annually in
      an effort to minimize the average coancestry in the population and limit
      inbreeding. We employed 12 microsatellite DNA markers to examine temporal genetic
      diversity in consecutive, discrete generations to determine the effects of
      intensive genetic management on the population and to quantify the amount of wild
      genetic diversity present within each captive generation. Wild fish are
      incorporated into the captive population each generation to minimize genetic
      drift, and 91% of the original founders are still represented in the F(3)
      generation. The average mean kinship in the third generation in captivity was
      0.0035. There was no evidence of significant genetic divergence of the captive
      population from the wild population. The results of this study yield management
      insights into the practical application of genetic management plans for captive
      populations and conservation hatcheries, in an attempt to preserve the genetic
      integrity of endangered species.

PMID- 23125403
TI  - Balancing a cline by influx of migrants: a genetic transition in water frogs of
      eastern Greece.
AB  - Variation patterns of allozymes and of ND3 haplotypes of mitochondrial DNA reveal
      a zone of genetic transition among western Palearctic water frogs extending
      across northeastern Greece and European Turkey. At the western end of the zone,
      allozymes characteristic of Central European frogs known as Pelophylax ridibundus
      predominate, whereas at the eastern end, alleles characteristic of western
      Anatolian water frogs (P. cf. bedriagae) prevail. The ND3 haplotypes reveal 2
      major clades, 1 characteristic of Anatolian frogs, the other of European; the
      European clade itself has distinct eastern and western subclades. Both the 2
      major clades and the 2 subclades overlap within the transition zone. Using
      Bayesian model selection methods, allozyme data suggest considerable immigration
      into the Nestos River area from eastern and western populations. In contrast, the
      ND3 data suggest that migration rates are so high among all locations that they
      form a single panmictic unit; the best model for allozymes is second best for
      mitochondrial DNA (mtDNA). Nuclear markers (allozymes), which have roughly 4
      times as deep a coalescent history as mtDNA data and thus may reflect patterns
      over a longer time, indicate that eastern and western refugial populations have
      expanded since deglaciation (in the last 10,000 years) and have met near the
      Nestos River, whereas the mtDNA with its smaller effective population size has
      already lost the signal of partitioning into refugia.

PMID- 23125406
TI  - Rapid characterization of mitochondrial genome rearrangements in Australian
      songbirds using next-generation sequencing technology.
AB  - Using next-generation sequencing technology, we describe the complete
      mitochondrial genomes for 5 Australian passerine birds (Epthianura albifrons,
      Petroica phoenicea, Petroica goodenovii, Petroica boodang, and Eopsaltria
      australis). We successfully assemble each mitogenome de novo using just 1/8th of
      a Roche GL FSX 454 pyrosequencing plate. From the assembled mitogenomes, we
      identify 2 different mitochondrial gene arrangements in the region spanning 5'-3'
      from Cytochrome B to 12s RNA. These gene arrangements represent 2 of the 4 known
      avian mitochondrial gene arrangements. Our results, together with other
      previously described avian mitogenomes, highlight that certain mitochondrial
      rearrangements appear to have arisen multiple times.

PMID- 23125407
TI  - Historical and anthropogenic factors affecting the population genetic structure
      of Ontario's inland lake populations of Walleye (Sander vitreus).
AB  - Populations existing in formerly glaciated areas often display composite
      historical and contemporary patterns of genetic structure. For Canadian
      freshwater fishes, population genetic structure is largely reflective of
      dispersal from glacial refugia and isolation within drainage basins across a
      range of scales. Enhancement of sport fisheries via hatchery stocking programs
      and other means has the potential to alter signatures of natural evolutionary
      processes. Using 11 microsatellite loci genotyped from 2182 individuals, we
      analyzed the genetic structure of 46 inland lake walleye (Sander vitreus)
      populations spanning five major drainage basins within the province of Ontario,
      Canada. Population genetic analyses coupled with genotype assignment allowed us
      to: 1) characterize broad- and fine-scale genetic structure among Ontario walleye
      populations; and 2) determine if the observed population divergence is primarily
      due to natural or historical processes, or recent anthropogenic events. The
      partitioning of genetic variation revealed higher genetic divergence among lakes
      than among drainage basins or proposed ancestries-indicative of relatively high
      isolation among lakes, study-wide. Walleye genotypes were clustered into three
      major groups, likely reflective of Missourian, Mississippian, and Atlantic
      glacial refugial ancestry. Despite detectable genetic signatures indicative of
      anthropogenic influences, province-wide spatial genetic structure remains
      consistent with the hypothesis of dispersal from distinct glacial refugia and
      subsequent isolation of lakes within primary drainage basins. Our results provide
      a novel example of minimal impacts from fishery enhancement to the broad-scale
      genetic structure of inland fish populations.

PMID- 23125408
TI  - Genealogy and Demographic History of a Widespread Amphibian throughout Indochina.
AB  - Relatively little is known about spatial patterns of cryptic diversity in
      tropical species and the processes that generate them. Few studies examine the
      geographic distribution of genetic lineages in Southeast Asia, an area
      hypothesized to harbor substantial cryptic diversity. We investigated the
      evolutionary history of Asian tree frogs of the Polypedates leucomystax complex
      (n = 172) based on 1800 bp of the mtDNA genes ND1 and cytochrome b and tested
      hypotheses pertaining to climate, geology, and dispersal patterns. Analyses
      revealed substantial genetic diversity and lineage divergence throughout the
      region with evidence for widespread sympatric lineages and a general north versus
      south clustering. Relaxed molecular clock analysis and tests for demographic
      expansion identified an initial cladogenesis during the Miocene with subsequent
      Plio-Pleistocene diversification, with the former corresponding to periods of
      increased aridity and the onset of monsoonal weather systems. Rates of
      diversification were relatively constant until the Early Pleistocene when rates
      increased exponentially. We found equivocal evidence for isolation-by-distance
      and a potential role of some landscape features as partial barriers to dispersal.
      Finally, our analyses showed that divergence between insular and mainland
      populations occurred before Homo sapiens colonized Southeast Asia, suggesting
      that historical human-mediated dispersal did not drive insular diversification.
      Our results suggested that demographic expansion in the Late Pleistocene resulted
      in widespread sympatric lineages in the P. leucomystax complex throughout
      southern China and Indochina and further clarified the evolutionary history of
      lineages within P. leucomystax.

PMID- 23125409
TI  - Genetic relationships of extant brown bears (Ursus arctos) and polar bears (Ursus
      maritimus).
AB  - Polar bears (Ursus maritimus) and brown bears (Ursus arctos) are closely related
      species for which extensive mitochondrial and nuclear phylogenetic comparisons
      have been made. We used previously published genotype data for 8 microsatellite
      DNA loci from 930 brown bears in 19 populations and 473 polar bears in 16
      populations to compare the population genetic relationships of extant populations
      of the species. Genetic distances (Nei standard distance = 1.157), the proportion
      of private alleles (52% of alleles are not shared by the species), and Bayesian
      cluster analysis are consistent with morphological and life-history
      characteristics that distinguish polar bears and brown bears as different species
      with little or no gene flow among extant populations.

PMID- 23125410
TI  - The role of men's physical attractiveness in women's perceptions of sexual risk:
      danger or allure?
AB  - The rate of casual sexual encounters is increasing on college campuses. To
      decrease sexual risk behavior, information used to judge sexual risk in others
      needs to be identified. Women rated male targets on willingness to have
      unprotected sex with the target and likelihood that the target has a sexually
      transmitted infection. Physical attractiveness was the strongest predictor of
      ratings, accounting for all the target variance in willingness to have
      unprotected sex. However, risk factors reported by the target were inconsistent
      predictors of perceived sexual risk. Findings are discussed within the context of
      safer sex interventions for college students. 

PMID- 23125411
TI  - Population structure of the Gulf pipefish in and around Mobile Bay and the
      northern Gulf of Mexico.
AB  - The genetic structure of inshore aquatic populations can be influenced by a
      number of factors, including coastal configurations, flow rates, and local
      adaptation. Properties such as salinity and temperature can differ significantly
      along the coasts and into the bays and rivers that contribute to these systems.
      Within these environments, low migratory euryhaline species provide a unique
      system to examine how these factors influence population structure, even when
      these populations are continuously distributed. In this study, we utilized
      microsatellite data to assess the population structure of 7 Gulf pipefish
      populations located in and around Mobile Bay and the northern Gulf of Mexico.
      Global F  (ST) values (F  (ST) = 0.025) suggest moderate levels of genetic
      structure among the populations. Local genetic structure was present among all
      coastal pipefish populations. Significant levels of genetic structure were also
      observed between coastal and estuarine populations (P < 0.05), with bay
      populations being distinct from their coastal counterparts. Cluster analysis
      suggests 2 parental populations, with one consisting mainly of estuarine
      individuals and the other comprising mainly coastal individuals. However,
      although these populations were genetically distinct, the genetic data also
      suggested moderate levels of migration between coastal and estuarine areas. We
      suggest that the differentiation between these populations is likely due to the
      colonization of individuals from coastal populations followed by limited
      dispersal out of the bay. It is also possible that different selective pressures
      between coastal and estuarine habitats may be contributing to the genetic
      differences between these populations.

PMID- 23125412
TI  - IFN-gamma limits Th9-mediated autoimmune inflammation through dendritic cell
      modulation of IL-27.
AB  - IL-9-producing Th9 cells have been associated with autoimmune diseases, such as
      experimental autoimmune encephalitis. However, the factors that negatively
      regulate Th9 cells during autoimmune inflammation are unclear. In this article,
      we show that IFN-gamma inhibits Th9 differentiation both in vitro and in vivo.
      This suppressive activity was dependent on the transcription factor STAT-1. In
      addition to its direct inhibitory effect on Th9 differentiation, IFN-gamma
      suppressed Th9 cells through the induction of IL-27 from dendritic cells. In
      vitro, treatment of naive CD4(+) T cells with IL-27 suppressed the development of
      Th9 cells, which was partially dependent on the transcription factors STAT-1 and
      T-bet. Moreover, IL-27 treatment completely abrogated the encephalitogenicity of
      Th9 cells in the experimental autoimmune encephalomyelitis model. Thus, our
      results identify a previously unknown mechanism by which IFN-gamma limits Th9
      mediated autoimmune inflammation through dendritic cell modulation of IL-27.

PMID- 23125413
TI  - IL-10 produced by induced regulatory T cells (iTregs) controls colitis and
      pathogenic ex-iTregs during immunotherapy.
AB  - "Natural" regulatory T cells (nTregs) that express the transcription factor Foxp3
      and produce IL-10 are required for systemic immunological tolerance. "Induced"
      regulatory T cells (iTregs) are nonredundant and essential for tolerance at
      mucosal surfaces, yet their mechanisms of suppression and stability are unknown.
      We investigated the role of iTreg-produced IL-10 and iTreg fate in a treatment
      model of inflammatory bowel disease. Colitis was induced in Rag1(-/-) mice by the
      adoptive transfer of naive CD4(+) T cells carrying a nonfunctional Foxp3 allele.
      At the onset of weight loss, mice were treated with both iTregs and nTregs where
      one marked subset was selectively IL-10 deficient. Body weight assessment,
      histological scoring, cytokine analysis, and flow cytometry were used to monitor
      disease activity. Transcriptional profiling and TCR repertoire analysis were used
      to track cell fate. When nTregs were present but IL-10 deficient, iTreg-produced
      IL-10 was necessary and sufficient for the treatment of disease, and vice versa.
      Invariably, ~85% of the transferred iTregs lost Foxp3 expression (ex-iTregs) but
      retained a portion of the iTreg transcriptome, which failed to limit their
      pathogenic potential upon retransfer. TCR repertoire analysis revealed no clonal
      relationships between iTregs and ex-iTregs, either within mice or between mice
      treated with the same cells. These data identify a dynamic IL-10-dependent
      functional reciprocity between regulatory T cell subsets that maintains mucosal
      tolerance. The niche supporting stable iTregs is limited and readily saturated,
      which promotes a large population of ex-iTregs with pathogenic potential during
      immunotherapy.

PMID- 23125414
TI  - Mechanism of action of inhibition of allergic immune responses by a novel
      antedrug TLR7 agonist.
AB  - Triggering innate immune responses through TLRs is expected to be a novel
      therapeutic strategy for the treatment of allergic diseases. TLR agonists are
      able to modulate Th2 immune responses through undefined mechanisms. We
      investigated the mechanism of action of the suppression of Th2 immune responses
      with a novel antedrug TLR7 agonist. The antedrug is rapidly metabolized by plasma
      esterases to an acid with reduced activity to limit systemic responses. Topical
      administration of this compound inhibited features of the allergic airway
      inflammatory response in rat and murine allergic airways model. Type I IFN played
      a role in the suppression of Th2 cytokines produced from murine splenocytes.
      Inhibition of Th2 immune responses with the antedrug TLR7 agonist was shown to be
      via a type I IFN-dependent mechanism following short-term exposure to the
      compound, although there might be type I IFN-independent mechanisms following
      long-term exposure. We have demonstrated that local type I IFN signaling and
      plasmacytoid dendritic cells, but not Th1 immune responses, are required for in
      vivo efficacy against murine airway Th2-driven eosinophilia. Furthermore,
      migration of dendritic cell subsets into the lung was related to efficacy and is
      dependent on type I IFN signaling. Thus, the mechanism of action at the cytokine
      and cellular level involved in the suppression of Th2 allergic responses has been
      characterized, providing a potential new approach to the treatment of allergic
      disease.

PMID- 23125415
TI  - Integrins alphavbeta3 and alpha4beta1 act as coreceptors for fractalkine, and the
      integrin-binding defective mutant of fractalkine is an antagonist of CX3CR1.
AB  - The membrane-bound chemokine fractalkine (FKN, CX3CL1) on endothelial cells plays
      a role in leukocyte trafficking. The chemokine domain (FKN-CD) is sufficient for
      inducing FKN signaling (e.g., integrin activation), and FKN-CD binds to its
      receptor CX3CR1 on leukocytes. Whereas previous studies suggest that FKN-CD does
      not directly bind to integrins, our docking simulation studies predicted that FKN
      CD directly interacts with integrin alpha(v)beta(3). Consistent with this
      prediction, we demonstrated that FKN-CD directly bound to alpha(v)beta(3) and
      alpha(4)beta(1) at a very high affinity (K(D) of 3.0 * 10(-10) M to
      alpha(v)beta(3) in 1 mM Mn(2+)). Also, membrane-bound FKN bound to integrins
      alpha(v)beta(3) and alpha(4)beta(1), suggesting that the FKN-CD/integrin
      interaction is biologically relevant. The binding site for FKN-CD in
      alpha(v)beta(3) was similar to those for other known alpha(v)beta(3) ligands.
      Wild-type FKN-CD induced coprecipitation of integrins and CX3CR1 in U937 cells,
      suggesting that FKN-CD induces ternary complex formation (CX3CR1, FKN-CD, and
      integrin). Based on the docking model, we generated an integrin-binding defective
      FKN-CD mutant (the K36E/R37E mutant). K36E/R37E was defective in ternary complex
      formation and integrin activation, whereas K36E/R37E still bound to CX3CR1. These
      results suggest that FKN-CD binding to CX3CR1 is not sufficient for FKN
      signaling, and that FKN-CD binding to integrins as coreceptors and the resulting
      ternary complex formation are required for FKN signaling. Notably, excess
      K36E/R37E suppressed integrin activation induced by wild-type FKN-CD and
      effectively suppressed leukocyte infiltration in thioglycollate-induced
      peritonitis. These findings suggest that K36E/R37E acts as a dominant-negative
      CX3CR1 antagonist and that FKN-CD/integrin interaction is a novel therapeutic
      target in inflammatory diseases.

PMID- 23125416
TI  - CCR1-mediated STAT3 tyrosine phosphorylation and CXCL8 expression in THP-1
      macrophage-like cells involve pertussis toxin-insensitive Galpha(14/16) signaling
      and IL-6 release.
AB  - Agonists of CCR1 contribute to hypersensitivity reactions and atherosclerotic
      lesions, possibly via the regulation of the transcription factor STAT3. CCR1 was
      demonstrated to use pertussis toxin-insensitive Galpha(14/16) to stimulate
      phospholipase Cbeta and NF-kappaB, whereas both Galpha(14) and Galpha(16) are
      also capable of activating STAT3. The coexpression of CCR1 and Galpha(14/16) in
      human THP-1 macrophage-like cells suggests that CCR1 may use Galpha(14/16) to
      induce STAT3 activation. In this study, we demonstrated that a CCR1 agonist,
      leukotactin-1 (CCL15), could indeed stimulate STAT3 Tyr(705) and Ser(727)
      phosphorylation via pertussis toxin-insensitive G proteins in PMA-differentiated
      THP-1 cells, human erythroleukemia cells, and HEK293 cells overexpressing CCR1
      and Galpha(14/16). The STAT3 Tyr(705) and Ser(727) phosphorylations were
      independent of each other and temporally distinct. Subcellular fractionation and
      confocal microscopy illustrated that Tyr(705)-phosphorylated STAT3 translocated
      to the nucleus, whereas Ser(727)-phosphorylated STAT3 was retained in the cytosol
      after CCR1/Galpha(14) activation. CCL15 was capable of inducing IL-6 and IL-8
      (CXCL8) production in both THP-1 macrophage-like cells and HEK293 cells
      overexpressing CCR1 and Galpha(14/16). Neutralizing Ab to IL-6 inhibited CCL15
      mediated STAT3 Tyr(705) phosphorylation, whereas inhibition of STAT3 activity
      abolished CCL15-activated CXCL8 release. The ability of CCR1 to signal through
      Galpha(14/16) provides a linkage for CCL15 to regulate IL-6/STAT3-signaling
      cascades, leading to expression of CXCL8, a cytokine that is involved in
      inflammation and the rupture of atherosclerotic plaque.

PMID- 23125417
TI  - Migrating lymph dendritic cells contain intracellular CD40 that is mobilized to
      the immunological synapse during interactions with antigen-specific T
      lymphocytes.
AB  - Steady state migrating rat lymph dendritic cells (LDC) are semimature, expressing
      high levels of surface MHC class II, but low levels of surface costimulatory
      molecules. In this study, we show that surface CD40 is not detectable, but LDC
      contain intracellular CD40. Multiple isoforms of CD40 were detected, including
      the type 1 isoform required for signal transduction. Culture of LDC with
      syngeneic T cells does not induce redistribution of cytoplasmic CD40. When LDC
      were cultured with naive allogeneic CD4(+) T lymphocytes, polarization of CD40 to
      the immune synapse occurred between 3 and 6 h postculture. By 24 h, although
      large numbers of T cells were engaged with LDC, CD40 could not be detected in LDC
      or at the synapses. We conclude that migrating LDC contain stores of CD40 that
      can be mobilized rapidly to the sites of interaction with Ag-specific T cells.
      The disappearance of CD40 by 24 h may help in the regulation of T cell
      activation.

PMID- 23125418
TI  - Macrophage migration inhibitory factor promotes tumor growth and metastasis by
      inducing myeloid-derived suppressor cells in the tumor microenvironment.
AB  - The macrophage migration inhibitory factor (MIF), an inflammatory cytokine, is
      overexpressed in many solid tumors and is associated with poor prognosis. We
      previously identified inhibitors of MIF within a class of natural products with
      demonstrated anti-cancer activities. We therefore sought to determine how MIF
      contributes to tumor growth and progression. We show in this study that in murine
      tumors including the 4T1 model of aggressive, spontaneously metastatic breast
      cancer in immunologically intact mice, tumor-derived MIF promotes tumor growth
      and pulmonary metastasis through control of inflammatory cells within the tumor.
      Specifically, MIF increases the prevalence of a highly immune suppressive
      subpopulation of myeloid-derived suppressor cells (MDSCs) within the tumor. In
      vitro, MIF promotes differentiation of myeloid cells into the same population of
      MDSCs. Pharmacologic inhibition of MIF reduces MDSC accumulation in the tumor
      similar to MIF depletion and blocks the MIF-dependent in vitro differentiation of
      MDSCs. Our results demonstrate that MIF is a therapeutically targetable mechanism
      for control of tumor growth and metastasis through regulation of the host immune
      response and support the potential utility of MIF inhibitors, either alone or in
      combination with standard tumor-targeting therapeutic or immunotherapy
      approaches.

PMID- 23125419
TI  - Autotaxin emerges as a therapeutic target for idiopathic pulmonary fibrosis:
      limiting fibrosis by limiting lysophosphatidic acid synthesis.

PMID- 23125421
TI  - A novel, privacy-preserving cryptographic approach for sharing sequencing data.
AB  - OBJECTIVE: DNA samples are often processed and sequenced in facilities external
      to the point of collection. These samples are routinely labeled with patient
      identifiers or pseudonyms, allowing for potential linkage to identity and private
      clinical information if intercepted during transmission. We present a
      cryptographic scheme to securely transmit externally generated sequence data
      which does not require any patient identifiers, public key infrastructure, or the
      transmission of passwords. MATERIALS AND METHODS: This novel encryption scheme
      cryptographically protects participant sequence data using a shared secret key
      that is derived from a unique subset of an individual's genetic sequence. This
      scheme requires access to a subset of an individual's genetic sequence to acquire
      full access to the transmitted sequence data, which helps to prevent sample
      mismatch. RESULTS: We validate that the proposed encryption scheme is robust to
      sequencing errors, population uniqueness, and sibling disambiguation, and
      provides sufficient cryptographic key space. DISCUSSION: Access to a set of an
      individual's genotypes and a mutually agreed cryptographic seed is needed to
      unlock the full sequence, which provides additional sample authentication and
      authorization security. We present modest fixed and marginal costs to implement
      this transmission architecture. CONCLUSIONS: It is possible for genomics
      researchers who sequence participant samples externally to protect the
      transmission of sequence data using unique features of an individual's genetic
      sequence.

PMID- 23125422
TI  - Explaining accesses to electronic medical records using diagnosis information.
AB  - OBJECTIVE: Ensuring the security and appropriate use of patient health
      information contained within electronic medical records systems is challenging.
      Observing these difficulties, we present an addition to the explanation-based
      auditing system (EBAS) that attempts to determine the clinical or operational
      reason why accesses occur to medical records based on patient diagnosis
      information. Accesses that can be explained with a reason are filtered so that
      the compliance officer has fewer suspicious accesses to review manually. METHODS:
      Our hypothesis is that specific hospital employees are responsible for treating a
      given diagnosis. For example, Dr Carl accessed Alice's medical record because
      Hem/Onc employees are responsible for chemotherapy patients. We present metrics
      to determine which employees are responsible for a diagnosis and quantify their
      confidence. The auditing system attempts to use this responsibility information
      to determine the reason why an access occurred. We evaluate the auditing system's
      classification quality using data from the University of Michigan Health System.
      RESULTS: The EBAS correctly determines which departments are responsible for a
      given diagnosis. Adding this responsibility information to the EBAS increases the
      number of first accesses explained by a factor of two over previous work and
      explains over 94% of all accesses with high precision. CONCLUSIONS: The EBAS
      serves as a complementary security tool for personal health information. It
      filters a majority of accesses such that it is more feasible for a compliance
      officer to review the remaining suspicious accesses manually.

PMID- 23125423
TI  - Placing a primary arteriovenous fistula that works--more or less known aspects,
      new ideas.
AB  - Despite the pre-operative availability of well-defined criteria to create a
      primary arteriovenous fistula (AVF) a high early failure/missing maturation is
      complained worldwide. Based on new results from basic research using numerical
      techniques, the authors try to guide attention to a widely neglected field in
      published data: the unremarkable, small, but essential surgical details in
      creating a successful AVF. The aim is to describe their significance and to give
      them a place in a cross-border context.

PMID- 23125424
TI  - C3 glomerulonephritis and CFHR5 nephropathy.
AB  - Complement is an important aspect of defence against infection and its activation
      and regulation are finely balanced. Disordered complement regulation can lead to
      C3 glomerulonephritis (C3GN), which is characterized by complement (but not
      immunoglobulin) deposition in the glomerulus of the kidney. Although only
      recently recognized as a clinical entity, C3GN is important and elucidation of
      its molecular causes, by studies of single cases and families, has identified key
      proteins that protect the kidney from complement-mediated damage. The commonest
      cause of C3GN is complement factor H-related 5 (CFHR5) nephropathy, which is
      endemic in Greek Cypriots. Genetic evidence implicates some of the same
      complement regulators in the aetiology of common immune complex glomerular
      disorders such as IgA nephropathy and lupus nephritis. Importantly, therapeutic
      manipulation of the complement pathway is now feasible. An exciting challenge is
      to determine whether this can be applied to kidney diseases that are caused by
      complement dysregulation, and also whether they might be used to intervene in
      other kidney diseases.

PMID- 23125425
TI  - Comment on "constitutive nuclear localization of NFAT in Foxp3(+) regulatory T
      cells independent of calcineurin activity".

PMID- 23125427
TI  - Transfemoral endovascular treatment of atherosclerotic stenotic lesions of the
      left common carotid artery ostium: case series and review of the literature.
AB  - OBJECTIVE: Endovascular treatment of atherosclerotic stenosis of the left common
      carotid artery ostium (LCCAO) represents a technical challenge. Unlike stenting
      of other supra-aortic trunk lesions, LCCAO stenting is not able to be performed
      from a retrograde approach through the brachial artery. Stenting may be performed
      via a retrograde approach with a carotid artery cut-down or with total
      endovascular technique via a transfemoral approach. A consecutive case series is
      presented to demonstrate the feasibility and safety of the endovascular
      transfemoral LCCAO stenting technique. METHODS: Our prospectively maintained
      database of elective neuroendovascular procedures was searched for cases of LCCAO
      angioplasty and stenting for atherosclerotic stenosis performed between January
      2003 and April 2012. Cases identified were isolated and analyzed for clinical and
      anatomic data. The primary outcome of interest was the incidence of
      periprocedural (30-day) neurological or cardiopulmonary complications. RESULTS:
      Fourteen patients were treated with a transfemoral approach (mean arterial
      stenosis 72%; symptomatic lesions 86%). Six (43%) had tandem stenosis of the
      proximal left internal carotid artery. In these cases, embolic protection was
      used. Stent revascularization was a technical success in all 14 patients,
      resulting in <20% residual stenosis in each. One intraprocedural complication
      (transient ischemic attack) was noted in a patient with symptomatic stenosis. One
      additional patient was identified who was treated with retrograde stenting due to
      bilateral leg amputations and no femoral access, with no periprocedural
      complication. CONCLUSIONS: In our experience, transfemoral stenting of stenotic
      LCCAO lesions is feasible and no permanent neurological or cardiopulmonary
      sequelae occurred in 14 patients treated with this technique.

PMID- 23125426
TI  - Regulatory T cell induction, migration, and function in transplantation.
AB  - Regulatory T cells (Treg) are important in maintaining immune homeostasis and in
      regulating a variety of immune responses, making them attractive targets for
      modulating immune-related diseases. Success in using induction or transfer of
      Treg in mice to mediate transplant tolerance suggests Treg-based therapies as
      mechanisms of long-term drug-free transplant tolerance in human patients.
      Although more work is needed, critical analyses suggest that key factors in Treg
      induction, migration, and function are important areas to concentrate
      investigative efforts and therapeutic development. Elucidation of basic biology
      will aid in translating data gleaned from mice to humans so that Treg therapies
      become a reality for patients.

PMID- 23125428
TI  - Risk of contrast-induced nephropathy in patients undergoing endovascular
      treatment of acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: We report the incidence and risk factors for contrast
      induced nephropathy after the use of iodinated contrast for endovascular
      treatment of acute ischemic stroke. METHODS: A retrospective chart review was
      performed in 194 consecutive patients who underwent endovascular treatment for
      acute ischemic stroke between January 2006 and January 2011. No patients were
      excluded from treatment for elevated creatinine (Cr). Each patient received
      approximately 150 ml intra-arterial non-ionic low-osmolar contrast agent (Optiray
      320) during the endovascular procedure. Contrast-induced nephropathy (CIN) was
      defined according to the Acute Kidney Injury Network criteria as a relative
      increase of serum Cr 50% above the baseline or an absolute increase of 0.3 mg/dl
      at 48 h following the endovascular procedure. RESULTS: Of 194 patients (mean age
      65 +/- 14 years), 52% were women (n=100) and 25% (n=48) were diabetic. Baseline
      Cr levels for 191 patients ranged between 0.4 and 2.7 mg/dl. Three patients on
      chronic hemodialysis had baseline Cr levels ranging between 5.3 and 6.1 mg/dl. Cr
      was <= 1.5 mg/dl in 163 patients (84%) and >= 1.5 mg/dl in 31 (16%). Three of the
      191 patients (1.5%) developed CIN as noted from Cr measurements between baseline
      and within 48 h. One patient who developed an elevated Cr level had a known
      history of chronic renal insufficiency (Cr > 1.5 mg/dl) and two had baseline Cr
      levels within the normal range. An additional CT angiogram was obtained in 44
      patients, none of which developed CIN. Female gender and diabetes were not
      associated with a higher risk of developing CIN. CONCLUSIONS: The risk of
      developing CIN is low among patients with acute stroke who undergo emergency
      endovascular treatment. Treatment of acute stroke should be performed
      irrespective of Cr levels.

PMID- 23125429
TI  - Ultrashort imaging to reperfusion time interval arrests core expansion in
      endovascular therapy for acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: The shorter the time interval between the estimation of
      the ischemic core by imaging and reperfusion, the more likely that core expansion
      is minimized. We aimed to assess the feasibility of achieving an ultrashort
      imaging to reperfusion time in routine clinical practice. METHODS: The study
      subjects were a prospective cohort of patients with acute ischemic stroke treated
      with endovascular therapy in a tertiary center in whom an imaging to reperfusion
      time of <60 min was achieved. RESULTS: Imaging to reperfusion time of <60 min was
      accomplished in 11 patients. The median baseline National Institutes of Health
      Stroke Scale (NIHSS) score was 11 and the median baseline Alberta Stroke Program
      Early CT Score (ASPECTS) was 8. The median time interval from imaging to
      endovascular reperfusion was 47 min. The median ASPECTS score on the 24 h CT scan
      was also 8 and the median 24 h NIHSS score was 1. Upon discharge, 82% of patients
      achieved a modified Rankin scale score of <= 1. CONCLUSIONS: An imaging to
      endovascular reperfusion time of <60 min is feasible and resulted in minimal core
      expansion on follow-up imaging in patients with acute ischemic stroke.

PMID- 23125430
TI  - Genetic analyses of nickel tolerance in a North American serpentine endemic
      plant, Caulanthus amplexicaulis var. barbarae (Brassicaceae).
AB  - PREMISE OF THE STUDY: The evolution of metal tolerance in plants is an important
      model for studies of adaptation to environment, population genetics, and
      speciation. Here, we investigated nickel tolerance in the North American
      serpentine endemic Caulanthus amplexicaulis var. barbarae in comparison with its
      nonserpentine sister taxon C. amplexicaulis var. amplexicaulis. We hypothesized
      that the serpentine endemic would have a heritable growth advantage on nickel
      containing substrates. METHODS: We employed an artificial growth assay to
      quantify biomass accumulation. Study plants were crossed to create an F(2:3)
      population that was used to determine the heritability of nickel tolerance and to
      map quantitative trait loci (QTL). Nickel accumulation in both laboratory
      populations and native specimens was examined using energy-dispersive x-ray
      fluorescence (EDXRF). KEY RESULTS: The serpentine endemic had a dramatic growth
      advantage at concentrations of nickel >30 umol/L. Caulanthus amplexicaulis var.
      barbarae and its nonserpentine sister taxon both accumulated nickel to
      substantial levels. Nickel tolerance was highly heritable (h(2) = 0.59) and not
      associated with accumulation. The QTL analyses identified two major loci for
      nickel tolerance, on linkage group 2 (LG2) and linkage group 9 (LG9).
      CONCLUSIONS: In our study, nickel tolerance was determined by two major loci with
      large effects. At both loci, alleles from the serpentine parent conferred
      positive effects on nickel tolerance, suggesting that they are adaptive in the
      natural serpentine environment. The mechanism of nickel tolerance in the
      serpentine plant was not exclusion of nickel. Nickel tolerance may have an
      inducible component in C. amplexicaulis var. barbarae.

PMID- 23125431
TI  - Cereal grass pulvini: agronomically significant models for studying gravitropism
      signaling and tissue polarity.
AB  - Cereal grass pulvini have emerged as model systems that are not only valuable for
      the study of gravitropism, but are also of agricultural and economic
      significance. The pulvini are regions of tissue that are apical to each node and
      collectively return a reoriented stem to a more vertical position. They have
      proven to be useful for the study of gravisensing and response and are also
      providing clues about the establishment of polarity across tissues. This review
      will first highlight the agronomic significance of these stem regions and their
      benefits for use as model systems and provide a brief historical overview. A
      detailed discussion of the literature focusing on cell signaling and early
      changes in gene expression will follow, culminating in a temporal framework
      outlining events in the signaling and early growth phases of gravitropism in this
      tissue. Changes in cell wall composition and gene expression that occur well into
      the growth phase will be touched upon briefly. Finally, some ongoing research
      involving both maize and wheat pulvini will be introduced along with prospects
      for future investigations.

PMID- 23125432
TI  - Evolution of morphological traits in Verbenaceae.
AB  - PREMISE OF THE STUDY: A new infrafamilial circumscription of the Verbenaceae with
      eight tribes: Casselieae, Citharexyleae, Duranteae, Lantaneae, Neospartoneae,
      Petreeae, Priveae, and Verbeneae, has been recently proposed, on the basis of
      molecular phylogenetic studies. Two genera, Dipyrena and Rhaphithamnus, remain
      unplaced. The aim of this work is to reconstruct the evolutionary history of
      morphological characters traditionally employed in the classification of the
      Verbenaceae, with special attention to tribes Verbeneae and Lantaneae. METHODS:
      Twenty-one characters, related to habit and vegetative morphology, inflorescence
      and floral morphology, ovary and fruit morphology, as well as chromosome number,
      were optimized over a molecular phylogeny of Verbenaceae. KEY RESULTS: All tribes
      are supported by at least one morphological trait except tribes Duranteae and
      Citharexyleae. Suffrutescent habit, sessile flowers, and four cluses are
      synapomorphies for tribe Verbeneae. Gynoecium with short style and entire stigma
      are synapomorphic traits for tribe Lantaneae. Sessile flowers and unicarpellate
      ovaries are morphological synapomorphies for the new tribe Neospartoneae.
      Suffrutescent habit is a synapomorphic trait for tribe Priveae. Homothetic
      pleiobotrya and absence of the adaxial staminode are synapomorphic traits for
      tribe Casselieae. Undivided fleshy fruits are probably a synapomorphic trait for
      tribe Petreeae. Putative plesiomorphies for the ancestor of the Verbenaceae are
      discussed as well as synapomorphic traits within other Verbenaceae clades.
      CONCLUSIONS: Many of the characters traditionally employed in classification have
      proven to be very homoplastic, or have been shown not to support relationships
      within the family. Moreover, traditional assumptions concerning character
      polarity have in some cases been shown to be incorrect.

PMID- 23125433
TI  - Low phosphate alters lateral root setpoint angle and gravitropism.
AB  - PREMISE OF THE STUDY: Lateral roots, responsible for water and nutrient uptake,
      maintain nonvertical angles throughout development. Soil phosphate is one
      limiting nutrient for plant growth that is known to induce changes to root system
      architecture, such as increased lateral root formation. This study seeks to
      determine whether phosphate concentration affects lateral root orientation in
      addition to its previously described influences on root architecture. METHODS:
      Images of intact Arabidopsis root systems were recorded for 24 h, and lateral
      root tip angles were measured for wild-type and mutant pgm-1 and pin3-1 roots on
      a full or low phosphate medium. Setpoint angles of unstimulated root systems were
      determined, as were gravitropic responses of lateral roots over time. KEY
      RESULTS: The root system setpoint angles of wild-type and mutant pin3-1 roots
      showed a shift toward a more vertical orientation on low orthophosphate (Pi)
      medium. The gravitropic responses of both pgm-1 and pin3-1 roots on low Pi medium
      was elevated relative to control Pi medium. Mutations in two phosphate
      transporters with high levels of expression in the root showed a gravitropic
      response similar to wild-type roots grown on low Pi, supporting a role for Pi
      status in regulating lateral root gravitropism. CONCLUSIONS: Lateral root
      orientation and gravitropism are affected by Pi status and may provide an
      important additional parameter for describing root responses to low Pi. The data
      also support the conclusion that gravitropic setpoint angle reacts to nutrient
      status and is under dynamic regulation.

PMID- 23125434
TI  - Zamia (Cycadales: Zamiaceae) on Puerto Rico: asymmetric genetic differentiation
      and the hypothesis of multiple introductions.
AB  - PREMISE OF THE STUDY: This study of Zamia in Puerto Rico is the most intensive
      population genetics investigation of a cycad to date in terms of number of
      markers, and one of few microsatellite DNA studies of plants from the highly
      critical Caribbean biodiversity hotspot. Three distinctive Zamia taxa occur on
      the island: Z. erosa on the north coast, and Z. portoricensis and Z. pumila, both
      in the south. Their relationships are largely unknown. We tested three hypotheses
      about their genetic diversity, including the possibility of multiple
      introductions. METHODS: We used 31 microsatellite loci across 10 populations and
      analyzed the data with AMOVA, Bayesian clustering, and ABC coalescent modeling.
      KEY RESULTS: Puerto Rican zamias exhibit an amalgam of patterns of genetic
      differentiation that have been reported for cycads. Overall, the taxa are
      slightly inbred, with high infra-populational variation and little evidence of
      recent bottlenecks. Zamia erosa exhibits a more than threefold greater degree of
      population differentiation than the other two taxa. Admixture is evident only
      between Z. portoricensis and Z. pumila. Zamia portoricensis is inferred to be the
      youngest taxon on the island, on the basis of estimates of coalescence time and
      effective population size. A selective sweep may be underway in a small
      population of Z. erosa in a saline environment. CONCLUSIONS: Zamia erosa may
      represent an independent introduction into Puerto Rico; Z. portoricensis and Z.
      pumila fit a scenario of allopatric speciation. This will be explored further in
      the context of genetic analysis across the entire Caribbean region.

PMID- 23125435
TI  - Symplasmic, long-distance transport in xylem and cambial regions in branches of
      Acer pseudoplatanus (Aceraceae) and Populus tremula x P. tremuloides
      (Salicaceae).
AB  - PREMISE OF THE STUDY: The picture of how long-distance transport proceeds in
      trees is still far from being complete. Beside the apoplasmic pathway, transport
      undoubtedly also takes place within the system of living cells in the secondary
      xylem and cambial region. Because detailed, thorough studies of the symplasmic
      routes in woody branches, using direct localization with fluorescent tracers, had
      not been done, here we focused on the main routes of long-distance symplasmic
      transport in xylem and cambial tissues and analyzed in detail tracer distribution
      in the rays on the extended cambial surface in branches of Acer pseudoplatanus
      and Populus tremula *P. tremuloides. METHODS: Fluorescent tracers were loaded
      into branches through the vascular system, then their distribution in xylem and
      cambial regions was analyzed. KEY RESULTS: Tracer signal was present in the
      symplast of axial and radial xylem parenchyma cells and in both types of cambial
      cells. The living cells of xylem parenchyma and of the cambium were
      symplasmically interconnected via xylem rays. Tracer distribution in rays was
      uneven on the extended cambial surface; cambial regions with intensively or
      sparsely dyed rays alternated along the vertical axis of analyzed branches.
      CONCLUSIONS: Symplasmic, long-distance transport is present between the living
      cells of xylem and the cambial region in woody branches. The uneven distribution
      of fluorescent tracers in cambial rays along the stems is surprising and suggests
      the presence of an intrinsic pattern caused by an unknown mechanism.

PMID- 23125436
TI  - Association between the geographic distribution during the last glacial maximum
      of Asian wild rice, Oryza rufipogon (Poaceae), and its current genetic variation.
AB  - PREMISE OF THE STUDY: The combination of traditional population genetic studies
      and species distribution modeling (SDM) provides many new insights in detecting
      phylogeographic signals. In Asian wild rice (Oryza rufipogon), the progenitor of
      cultivated Asian rice, geographical subdivision has been documented in many
      genetic studies although the root cause of this subdivision remains unknown.
      Surprisingly, environmental factors associated with the spatial and temporal
      distribution of O. rufipogon have rarely been examined. The aim of this study is
      to understand the historical distribution of O. rufipogon and its relationship to
      the current geographical pattern of genetic variation. METHODS: We used SDM to
      examine the present, past, and future distribution of O. rufipogon. The estimated
      distribution during the Last Glacial Maximum was then compared with genetic data
      from our previous work. KEY RESULTS: The predicted paleodistribution of O.
      rufipogon at the Last Glacial Maximum was separated into disconnected east and
      west ranges. This past distribution is consistent with the current geographic
      pattern of genetic variation, with two genetic groups that intergrade. Annual
      precipitation is the single factor that contributes most to SDM estimates. SDM
      predictions for 2080 indicate a general trend of increasing probability of
      presence and range expansion. CONCLUSIONS: (1) The historically disjunct
      distribution potentially contributes to the current genetic subdivision of O.
      rufipogon. (2) Water availability is an important factor that limits the
      distribution of O. rufipogon. (3) Global warming is a lesser threat than other
      human-mediated factors to the conservation of this endangered species.

PMID- 23125437
TI  - The emergency department action in smoking cessation (EDASC) trial: impact on
      cessation outcomes.
AB  - INTRODUCTION: The focus on acute care, time pressure, and lack of resources
      hamper the implementation of smoking cessation guidelines in the emergency
      department (ED). The purpose of this study was to determine whether an emergency
      nurse- initiated intervention based on the 5A's (Ask-Advise-Assess-Assist
      Arrange) framework improves quit rates. METHODS: We conducted a pre-post
      implementation trial in 789 adult smokers who presented to two EDs in Iowa
      between August 13, 2008 and August 4, 2010. The intervention focused on improving
      delivery of the 5A's by ED nurses and physicians using academic detailing,
      charting/reminder tools, and group feedback. Performance of ED cessation
      counseling was measured using a 5A's composite score (ranging from 0 to 5).
      Smoking status was assessed by telephone interview at 3- and 6-month follow-up
      (with biochemical confirmation in those participants who reported abstinence at 6
      month follow-up). RESULTS: Based on data from 650 smokers who completed the post
      ED interview, there was a significant improvement in the mean 5A's composite
      score for emergency nurses during the intervention period at both hospitals
      combined (1.51 vs. 0.88, difference = 0.63, 95% confidence interval [CI] [0.41,
      0.85]). At 6-month follow-up, 7-day point prevalence abstinence (PPA) was 6.8 and
      5.1% in intervention and preintervention periods, respectively (adjusted odds
      ratio [OR] = 1.7, 95% CI [0.99, 2.9]). CONCLUSIONS: It is feasible to improve the
      delivery of brief smoking cessation counseling by ED staff. The observed
      improvements in performance of cessation counseling, however, did not translate
      into statistically significant improvements in cessation rates. Further
      improvements in the effectiveness of ED cessation interventions are needed.

PMID- 23125438
TI  - Urban Chinese smokers from lower socioeconomic backgrounds face more barriers to
      quitting: results from the international tobacco control-China survey.
AB  - INTRODUCTION: Research findings on social disparities in barriers to quitting
      faced by smokers from mainly Western English-language countries may or may not
      generalize to smokers in China. This paper sought to determine whether nicotine
      dependence, quitting self-efficacy, quitting interest differ by socio-economic
      status (SES), and whether they mediate the relationship between SES and quitting
      behavior of urban Chinese smokers. METHODS: Data come from 7,309 adult smokers
      who participated in the first 3 waves of the International Tobacco Control-China
      survey conducted in 7 cities across China. The association of socio-economic
      indicators with nicotine dependence, quitting self-efficacy, quitting interest,
      and behavior was evaluated using generalized estimating equations models along
      with a formal test of mediational effects. RESULTS: The SES index indicated that
      those from lower SES were significantly more addicted (p < .001), less confident
      (p < .001), and less interested in quitting (p < .05). This finding was
      replicated by education and employment status, but it was not clearly related to
      income. Mediational analyses revealed that the effects of SES on making quit
      attempts and quit success among those who tried were indirect. For quit attempts,
      self-efficacy, interest to quit, and heaviness of smoking index (HSI) were all
      significant mediators of the SES effect (p < .001), but for maintenance, only HSI
      was a significant mediator (p < .001). CONCLUSIONS: Urban Chinese smokers from
      lower socio- economic backgrounds experience greater levels of psychological and
      behavioral barriers to quitting than their counterparts from higher socio
      economic backgrounds and as such, they need more help to quit and do so
      successfully.

PMID- 23125439
TI  - A prospective study of serum 25-hydroxyvitamin d levels and mortality among
      African Americans and non-African Americans.
AB  - The beneficial biologic effects attributed to vitamin D suggest a potential to
      influence overall mortality. Evidence addressing this hypothesis is limited,
      especially for African Americans who have a high prevalence of vitamin D
      insufficiency. The authors conducted a nested case-control study within the
      prospective Southern Community Cohort Study to relate baseline serum levels of 25
      hydroxyvitamin D (25(OH)D) with subsequent mortality. Cases were 1,852
      participants who enrolled from 2002 to 2009 and died >12 months postenrollment.
      Controls (n = 1,852) were matched on race, sex, age, enrollment site, and blood
      collection date. The odds ratios for quartile 1 (<10.18 ng/mL) versus quartile 4
      (>21.64 ng/mL) levels of 25(OH)D were 1.60 (95% confidence interval (CI): 1.20,
      2.14) for African Americans and 2.11 (95% CI: 1.39, 3.21) for non-African
      Americans. The effects were strongest for circulatory disease death, where
      quartile 1 versus quartile 4 odds ratios were 2.53 (95% CI: 1.44, 4.46) and 3.25
      (95% CI: 1.33, 7.93) for African Americans and non-African Americans,
      respectively. The estimated odds of total mortality were minimized in the 25(OH)D
      range of 35-40 ng/mL. These findings provide support for the hypothesis that
      vitamin D status may have an important influence on mortality for both African
      Americans and non-African Americans.

PMID- 23125440
TI  - A mutation in the promoter of the chicken beta,beta-carotene 15,15'-monooxygenase
      1 gene alters xanthophyll metabolism through a selective effect on its mRNA
      abundance in the breast muscle.
AB  - A polymorphism in the promoter of the beta,beta-carotene 15,15'-monooxygenase 1
      (BCMO1) gene recently was identified in an experimental cross between 2 chicken
      lines divergently selected on growth rate and found to be associated with
      variations in the yellow color of the breast meat. In this study, the effects of
      the polymorphism on several aspects of carotenoid metabolism were evaluated in
      chickens sharing the same genetic background except for their genotype at the
      BCMO1 locus. We confirmed that BCMO1 mRNA abundance varied (P < 0.001) between
      the 2 homozygous genotypes (GG << AA) and in the pectoralis major muscle. By
      contrast, BCMO1 mRNA expression was not affected (P > 0.05) by the polymorphism
      in the duodenum, liver, or sartorius muscle. The breast meat of GG chickens was
      more (P < 0.001) yellow and richer in lutein (P < 0.01) and zeaxanthin (P < 0.05)
      compared to that of AA chickens whereas these variables did not differ (P > 0.05)
      in the other tissues tested. The GG were also characterized by reduced (P < 0.01)
      plasma lutein and zeaxanthin concentrations than AA without affecting plasma and
      tissue content of fat-soluble vitamins A and E. As lutein and zeaxanthin are
      usually not considered as substrates of the BCMO1 enzyme, the impact of BCMO1
      polymorphism on the activity of other genes involved in carotenoid transport
      (SCARB1 and CD36 encoding the scavenger receptor class B type I and the cluster
      determinant 36, respectively) and metabolism (BCDO2 encoding beta,beta-carotene
      9',10'-dioxygenase 2) was evaluated. The BCMO1 polymorphism did not affect mRNA
      abundance of BCDO2, SCARB1, or CD36, regardless of tissue considered. Taken
      together, these results indicated that a genetic variant of BCMO1 specifically
      changes lutein and zeaxanthin content in the chicken plasma and breast muscle
      without impairing vitamin A and E metabolism.

PMID- 23125441
TI  - Application and assessment of a regular environmental monitoring of the
      antineoplastic drug contamination level in pharmacies - the MEWIP project.
AB  - A large-scale study was carried out in order to determine the contamination level
      of antineoplastic drugs in pharmacies and to investigate the suitability and
      effects of wipe sample monitoring at regular intervals. A specific study design
      was developed. The 130 participating pharmacies were divided into a study and a
      control group, carrying out five and two wipe sampling cycles, respectively. The
      work practice was analyzed using questionnaires to identify factors that
      influence the contamination level. From 1269 wipe samples, 774 (61%) were
      contaminated with at least one of the analyzed cytotoxic drugs: cyclophosphamide,
      docetaxel, etoposide, 5-fluorouracil, gemcitabine, ifosfamide, methotrexate, and
      paclitaxel. A significant decrease of the contamination with cyclophosphamide and
      5-fluorouracil was observed in the study group. The Monitoring-Effect Study of
      Wipe Sampling in Pharmacies method has proven to be a reliable and affordable
      tool for contamination control. Based on the 90th percentile of the contamination
      values, a substance-independent performance-based guidance value of 0.1ng cm(-2)
      has been derived.

PMID- 23125442
TI  - Phosphorylation of mitogen-activated protein kinases contributes to interferon
      gamma production in response to Mycobacterium tuberculosis.
AB  - Immune control of Mycobacterium tuberculosis depends on interferon gamma (IFN
      gamma)-producing CD4(+) lymphocytes. Previous studies have shown that T cells
      from patients with tuberculosis produce less IFN-gamma, compared with healthy
      donors, in response to mycobacterial antigens, although IFN-gamma responses to
      mitogens are preserved. In this work, we found that M. tuberculosis-induced IFN
      gamma production by human T cells correlated with phosphorylation of the mitogen
      activated protein kinases (MAPKs), extracellular signal-regulated kinase (ERK),
      and p38. Moreover, the majority of IFN-gamma-producing T cells expressed
      signaling lymphocyte activation molecule (SLAM), and SLAM activation further
      increased ERK phosphorylation. Interestingly, patients with tuberculosis had
      delayed activation of ERK and p38, and this was most marked in patients with the
      poorest IFN-gamma responses (ie, low responders). Besides, SLAM signaling failed
      to phosphorylate ERK in low responders. Our findings suggest that activation of
      p38 and ERK, in part through SLAM, mediates T-cell IFN-gamma production in
      response to M. tuberculosis, a pathway that is defective in patients with
      tuberculosis.

PMID- 23125443
TI  - Characterization of humoral and cellular immune responses elicited by a
      recombinant adenovirus serotype 26 HIV-1 Env vaccine in healthy adults (IPCAVD
      001).
AB  - BACKGROUND: Adenovirus serotype 26 (Ad26) has been developed as a novel candidate
      vaccine vector for human immunodeficiency virus type 1 (HIV-1) and other
      pathogens. The primary safety and immunogenicity data from the Integrated
      Preclinical/Clinical AIDS Vaccine Development Program (IPCAVD) 001 trial, the
      first-in-human evaluation of a prototype Ad26 vector-based vaccine expressing
      clade A HIV-1 Env (Ad26.ENVA.01), are reported concurrently with this article.
      Here, we characterize in greater detail the humoral and cellular immune responses
      elicited by Ad26.ENVA.01 in humans. METHODS: Samples from the IPCAVD 001 trial
      were used for humoral and cellular immunogenicity assays. RESULTS: We observed a
      dose-dependent expansion of the magnitude, breadth, and epitopic diversity of Env
      specific binding antibody responses elicited by this vaccine. Antibody-dependent
      cell-mediated phagocytosis, virus inhibition, and degranulation functional
      activity were also observed. Env-specific cellular immune responses induced by
      the vaccine included multiple CD8(+) and CD4(+) T-lymphocyte memory
      subpopulations and cytokine secretion phenotypes, although cellular immune
      breadth was limited. Baseline vector-specific T-lymphocyte responses were common
      but did not impair Env-specific immune responses in this study. CONCLUSION:
      Ad26.ENVA.01 elicited a broad diversity of humoral and cellular immune responses
      in humans. These data support the further clinical development of Ad26 as a
      candidate vaccine vector. CLINICAL TRIALS REGISTRATION: NCT00618605.

PMID- 23125445
TI  - Schistosoma mansoni infection in preschool-aged children: development of
      immunoglobulin E and immunoglobulin G4 responses to parasite allergen-like
      proteins.
AB  - Specific immunoglobulin E (IgE) responses are upregulated during chronic
      schistosome infection and during allergy. These responses are tightly regulated
      during schistosomiasis. We have previously shown that IgE regulation depends on
      the extent and length of exposure to individual parasite allergen-like proteins.
      Here we compare the development of IgE and immunoglobulin G4 (IgG(4)) responses
      to the differentially expressed allergen-like proteins SmTAL1 and SmTAL2 among
      preschool-aged children from 2 villages with different levels of Schistosoma
      mansoni transmission. We found a lack of SmTAL1 responsiveness among all
      children, but evidence for IgG(4)-dependent IgE-SmTAL2 desensitization in both
      villages, occurring earlier among children from the village where the level of
      transmission was greater. Findings provide insights into the development and
      regulation of allergic-type immune responses.

PMID- 23125446
TI  - Use of human monoclonal antibodies to treat Chikungunya virus infection.
AB  - Chikungunya virus (CHIKV) is an alphavirus prevalent in tropical regions. It
      causes an acute febrile disease that, in elderly individuals and newborns, is
      often associated with severe complications. We previously reported the isolation
      and characterization of 2 human monoclonal antibodies neutralizing CHIKV in
      vitro: 5F10 and 8B10. Here, we tested their efficacy in vivo as prophylactic and
      therapeutic treatments of CHIKV infection in AGR129 mice. In both settings, 5F10
      and 8B10 were able to significantly delay CHIKV-driven lethality. Our results
      support the development of prophylactic and therapeutic treatments for CHIKV
      infection, using a combination of 5F10 and 8B10.

PMID- 23125444
TI  - First-in-human evaluation of the safety and immunogenicity of a recombinant
      adenovirus serotype 26 HIV-1 Env vaccine (IPCAVD 001).
AB  - BACKGROUND: We report the first-in-human safety and immunogenicity assessment of
      a prototype Ad26 vector-based human immunodeficiency virus (HIV) vaccine in
      humans. METHODS: Sixty Ad26-seronegative, healthy, HIV-uninfected subjects were
      enrolled in a randomized, double-blinded, placebo-controlled, dose-escalation
      phase 1 study. Five groups of 12 subjects received 10(9)-10(11) vp of the Ad26
      EnvA vaccine (N = 10/group) or placebo (N = 2/group) at weeks 0 and 24 or weeks
      0, 4, and 24. Safety and immunogenicity were assessed. RESULTS: Self-limited
      reactogenicity was observed after the initial immunization at the highest (10(11)
      vp) dose. No product-related SAEs were observed. All subjects who received the
      Ad26-EnvA vaccine developed Ad26 NAb titers, EnvA-specific enzyme-linked
      immunosorbent assays (ELISA) titers, and EnvA-specific enzyme-linked immunospot
      assays (ELISPOT) responses. These responses persisted at week 52. At week 28 in
      the 10(9), 10(10), 10(11) vp 3-dose and the 10(10) and 5 * 10(10) vp 2-dose
      groups, geometric mean EnvA ELISA titers were 6113, 12 470, 8545, 3470, and 9655
      and mean EnvA ELISPOT responses were 397, 178, 736, 196, and 1311 SFC/10(6)
      peripheral blood mononuclear cells, respectively. CONCLUSION: This Ad26 vectored
      vaccine was generally safe and immunogenic at all doses tested. Reactogenicity
      was minimal with doses of 5 * 10(10) vp or less. Ad26 is a promising new vaccine
      vector for HIV-1. CLINICAL TRIALS REGISTRATION: NCT00618605.

PMID- 23125447
TI  - Macrophage migration inhibitory factor deficiency is associated with impaired
      killing of gram-negative bacteria by macrophages and increased susceptibility to
      Klebsiella pneumoniae sepsis.
AB  - The cytokine macrophage migration inhibitory factor (MIF) is an important
      component of the early proinflammatory response of the innate immune system.
      However, the antimicrobial defense mechanisms mediated by MIF remain fairly
      mysterious. In the present study, we examined whether MIF controls bacterial
      uptake and clearance by professional phagocytes, using wild-type and MIF
      deficient macrophages. MIF deficiency did not affect bacterial phagocytosis, but
      it strongly impaired the killing of gram-negative bacteria by macrophages and
      host defenses against gram-negative bacterial infection, as shown by increased
      mortality in a Klebsiella pneumonia model. Consistent with MIF's regulatory role
      of Toll-like 4 expression in macrophages, MIF-deficient cells stimulated with
      lipopolysaccharide or Escherichia coli exhibited reduced nuclear factor kappaB
      activity and tumor necrosis factor (TNF) production. Addition of recombinant MIF
      or TNF corrected the killing defect of MIF-deficient macrophages. Together, these
      data show that MIF is a key mediator of host responses against gram-negative
      bacteria, acting in part via a modulation of bacterial killing by macrophages.

PMID- 23125448
TI  - Antibody against TcdB, but not TcdA, prevents development of gastrointestinal and
      systemic Clostridium difficile disease.
AB  - BACKGROUND: A dramatic increase in morbidity and mortality from Clostridium
      difficile infection (CDI) due to the recent emergence of virulent, antibiotic
      resistant strains has led to a search for alternatives to antibiotics, including
      vaccines and immune-based therapy that target the 2 key toxins-TcdA and TcdB.
      METHODS: We investigated the efficacy of specific human monoclonal antibodies
      (HuMab) and alpaca polyclonal antibodies against each toxin separately and in
      combination in the gnotobiotic piglet model of CDI. Additionally, the HuMab and
      polyclonal antibodies were exploited to investigate the precise contribution of
      each toxin to systemic and/or gastrointestinal (GI) tract disease. RESULTS: Our
      results indicate that TcdB is an important virulence factor associated with GI
      and systemic pathology. Administration of anti-TcdB antibody alone or with anti
      TcdA protected 100% of piglets from development of systemic CDI and minimized GI
      lesions. Conversely, 100% of piglets administered only anti-TcdA developed severe
      GI and systemic disease, with 67%-83% fatality, faring worse than placebo-treated
      control animals. CONCLUSIONS: These results highlight the importance of TcdB in
      the pathogenesis of CDI and the effectiveness of TcdB-specific antibody in
      treating CDI. However, the results raise new questions regarding the nature of
      TcdA interaction with therapeutic antibodies.

PMID- 23125456
TI  - Stem cell factor contributes to tumorigenesis of mast cells via an
      autocrine/paracrine mechanism.
AB  - Mastocytosis is a disease accompanied by the abnormal expansion and accumulation
      of mast cells. Although the D816V mutation is detected in most cases of systemic
      mastocytosis, the mutation is rarely observed in other forms of mastocytosis,
      such as cutaneous mastocytosis and mast cell leukemia/sarcoma, for which the
      mechanism of tumorigenesis remains unknown. In this study, we demonstrated a
      novel mechanism of mast cell tumorigenesis via SCF autocrine/paracrine release.
      SCF was highly expressed in a WT KIT-expressing HRMC line, contributing to the
      phosphorylation of KIT. Neutralization of external SCF using a neutralizing
      antibody or suppression of SCF production by RNA interference inhibited the
      growth of HRMC cells, indicating the essential role of SCF in cell proliferation.
      To the best of our knowledge, this is the first report to determine the
      significant contribution of SCF autoproduction to neoplastic proliferation of
      mast cells. These results indicate the possibility that targeting SCF production
      may become a novel treatment for mast cell malignancies.

PMID- 23125457
TI  - Integrin subtype-dependent CD18 cleavage under shear and its influence on
      leukocyte-platelet binding.
AB  - Previous studies showed that exposure of neutrophils to shear stress induces
      cysteine protease-mediated shedding of surface CD18 integrins involved in
      leukocyte-platelet interactions. Based on this, we hypothesized that, under
      noninflamed conditions, shear-induced CD18 cleavage is a control mechanism to
      minimize spontaneous leukocyte-platelet binding. For this purpose, we
      characterized the influence of shear on CD18 surface expression and platelet
      binding by the different leukocyte subsets. Shear stress elicited magnitude-
      (between 0 and 5 dyn/cm(2)) and time-dependent reductions in CD18 surface
      expression. This response was integrin- and cell type-specific, with neutrophils
      and monocytes exhibiting Mac-1 proteolysis but lymphocytes displaying LFA-1
      shedding. Correspondingly, platelet binding, through CD18-fibrinogen
      interactions, was also influenced by shear exposure in a leukocyte-dependent
      manner. After treatment with cysteine protease inhibitor E64, neutrophils, but
      neither monocytes nor lymphocytes, exhibited significantly (P<0.05) enhanced
      platelet binding and CD18 surface expression under shear. Furthermore, shear
      exposure significantly (P<0.05) inhibited binding of naive but not E64-treated
      neutrophils to fibrinogen. Combined, we provide first evidence that the CD18
      cleavage responses of neutrophils to shear interfere with fibrinogen binding and
      platelet adhesion. These findings have implications as it relates to the
      efficiency of leukocyte passage through the microcirculation.

PMID- 23125449
TI  - HIV nonnucleoside reverse transcriptase inhibitors and trimethoprim
      sulfamethoxazole inhibit plasmodium liver stages.
AB  - BACKGROUND: Although nonnucleoside reverse transcriptase inhibitors (NNRTIs) are
      usually part of first-line treatment regimens for human immunodeficiency virus
      (HIV), their activity on Plasmodium liver stages remains unexplored.
      Additionally, trimethoprim-sulfamethoxazole (TMP-SMX), used for opportunistic
      infection prophylaxis in HIV-exposed infants and HIV-infected patients, reduces
      clinical episodes of malaria; however, TMP-SMX effect on Plasmodium liver stages
      requires further study. METHODS: We characterized NNRTI and TMP-SMX effects on
      Plasmodium liver stages in vivo using Plasmodium yoelii. On the basis of these
      results, we conducted in vitro studies assessing TMP-SMX effects on the rodent
      parasites P. yoelii and Plasmodium berghei and on the human malaria parasite
      Plasmodium falciparum. RESULTS: Our data showed NNRTI treatment modestly reduced
      P. yoelii liver stage parasite burden and minimally extended prepatent period.
      TMP-SMX administration significantly reduced liver stage parasite burden,
      preventing development of patent parasitemia in vivo. TMP-SMX inhibited
      development of rodent and P. falciparum liver stage parasites in vitro.
      CONCLUSIONS: NNRTIs modestly affect liver stage Plasmodium parasites, whereas TMP
      SMX prevents patent parasitemia. Because drugs that inhibit liver stages target
      parasites when they are present in lower numbers, these results may have
      implications for eradication efforts. Understanding HIV drug effects on
      Plasmodium liver stages will aid in optimizing treatment regimens for HIV-exposed
      and HIV-infected infected patients in malaria-endemic areas.

PMID- 23125458
TI  - Effect of weight loss, independent of change in diet composition, on
      apolipoprotein AI kinetic in men with metabolic syndrome.
AB  - We investigated the effect of weight loss, independent of change in diet
      composition, on HDL and apoAI metabolism in men with metabolic syndrome (MetS).
      Subjects (19 men with MetS [NCEP-ATPIII]) were fed an isoenergetic Mediterranean
      style diet for 5 weeks (all foods provided). Participants then underwent a 20
      week free-living period during which they were counseled to restrict energy
      intake, after which they were again fed an isoenergetic Mediterranean-style diet
      for 5 weeks. At the end of the two controlled diets, participants received a
      single bolus of [5,5,5-(2)H(3)] (L)-leucine, and fasting blood samples were
      collected over a 96 h period. ApoAI kinetic was assessed using multicompartmental
      modeling of the tracer enrichment data. Participants achieved a 9.1 +/- 2.8%
      reduction in body weight (P < 0.001). Weight loss resulted in an increase in
      plasma HDL-cholesterol (HDL-C) concentrations of 6.0% (P = 0.059) and HDL(3)-C of
      7.9% (P = 0.045), attributable to a reduction in apoAI fractional catabolic rate
      (-7.8%; P = 0.046) with no change in apoAI production rate (2.2%; P = 0.58).
      These data indicate that weight loss, independent of variation in diet
      composition, increases plasma HDL primarily by delaying the catabolism of apoAI.

PMID- 23125459
TI  - Localization and regulation of pancreatic selenoprotein P.
AB  - Progressive loss of pancreatic beta-cell mass is a crucial feature of type 2
      diabetes mellitus. As beta-cells express very low amounts of the antioxidant
      enzymes catalase and glutathione peroxidase (GPx), they appear to be particularly
      vulnerable to oxidative damage in the pathogenesis of diabetes. Here, we
      investigated the pancreatic expression pattern and regulation of selenoprotein P
      (Sepp1), which may serve as an additional antioxidant enzyme inside and outside
      of cells. Sepp1 was detected in rodent pancreas by immunofluorescence and real
      time RT-PCR. Regulation of Sepp1 biosynthesis in INS-1 rat insulinoma cells was
      investigated by real-time RT-PCR, luciferase gene reporter assay, and
      immunoblotting. Sepp1 and Gpx1 gene expressions in rat pancreas were 58 and 22%
      respectively of the liver values. Pancreatic Sepp1 expression was restricted to
      the endocrine tissue, with Sepp1 being present in the alpha- and beta-cells of
      mouse islets. In INS-1 insulinoma cells, Sepp1 expression was stimulated by the
      selenium compound sodium selenate and diminished in the presence of high glucose
      (16.7 vs 5  mM) concentrations. Sepp1 mRNA stability was also lowered at 16.7  mM
      glucose. Moreover, Sepp1 mRNA levels were decreased in isolated murine islets
      cultured in high-glucose (22  mM) medium compared with normal glucose (5.5  mM)
      medium. Pancreatic Sepp1 expression was elevated upon treatment of mice with the
      beta-cell toxin streptozotocin. This study shows that pancreatic islets express
      relatively high levels of Sepp1 that may fulfill a function in antioxidant
      protection of beta-cells. Downregulation of Sepp1 expression by high glucose
      might thus contribute to glucotoxicity in beta-cells.

PMID- 23125460
TI  - Novel KIF7 mutations extend the phenotypic spectrum of acrocallosal syndrome.
AB  - BACKGROUND: Acrocallosal syndrome (ACLS) is a rare recessive disorder
      characterised by corpus callosum agenesis or hypoplasia, craniofacial
      dysmorphism, duplication of the hallux, postaxial polydactyly, and severe mental
      retardation. Recently, we identified mutations in KIF7, a key component of the
      Sonic hedgehog pathway, as being responsible for this syndrome. METHODS: We
      sequenced KIF7 in five suspected ACLS cases, one fetus and four patients, based
      on facial dysmorphism and brain anomalies. RESULTS: Seven mutations were
      identified at the KIF7 locus in these five cases, six of which are novel. We
      describe the first four compound heterozygous cases. In all patients, the
      diagnosis was suspected based on the craniofacial features, despite the absence
      of corpus callosum anomaly in one and of polydactyly in another. Hallux
      duplication was absent in 4/5 cases. CONCLUSIONS: These results show that ACLS
      has a variable expressivity and can be diagnosed even in the absence of the two
      major features, namely polydactyly or agenesis or hypoplasia of the corpus
      callosum. Facial dysmorphism with hypertelorism and prominent forehead in all the
      cases, as well as vermis dysgenesis with brainstem anomalies (molar tooth sign),
      strongly indicated the diagnosis. KIF7 should be tested in less typical patients
      in whom craniofacial features are suggestive of ACLS.

PMID- 23125462
TI  - Linear Solvation Energy Relationships in the Determination of Specificity and
      Selectivity of Stationary Phases.
AB  - The retention of fifty structurally different compounds has been studied using
      linear solvation energy relationships. Investigations were performed with the use
      of six various stationary phases with two mobile phases (50/50 % v/v
      methanol/water and 50/50 % v/v acetonitrile/water). Packing materials were home
      made and functionalized with octadecyl, alkylamide, cholesterol, alkyl-phosphate
      and phenyl molecules. This is the first attempt to compare all of these
      stationary phases synthesized on the same silica gel batch. Therefore, all of
      them may be compared in more complex and believable way, than it was performed
      earlier in former investigations. The phase properties (based on Abraham model)
      were used to the classification of stationary phases according to their
      interaction properties. The hydrophilic system properties s, a, b indicate
      stronger interactions between solute and mobile phase for most of the columns.
      Both e and v cause greater retention as a consequence of preferable interactions
      with stationary phase by electron pairs and cavity formation as well as
      hydrophobic bonds. However, alkyl-phosphate phase has different retention
      properties, as it was expressed by positive sign of s coefficient. It may be
      concluded that most important parameters influencing the retention of compounds
      are volume and hydrogen bond acceptor basicity. The LSER coefficients showed also
      the dependency on the type of organic modifier used as a mobile phase component.

PMID- 23125463
TI  - Effects of Individualized and Standardized Interventions on Middle School
      Students With Reading Disabilities.
AB  - This study reports the effectiveness of a year-long, small-group, tertiary (Tier
      3) intervention that examined 2 empirically derived but conceptually different
      treatments and a comparison condition. The researchers had randomly assigned all
      students to treatment or comparison conditions. The participants were seventh-
      and eighth-grade students from the previous year who received an intervention and
      did not meet exit criteria. The researchers assigned them to one of two
      treatments: standardized (n = 69) or individualized (n = 71) for 50 min a day, in
      group sizes of 5, for the entire school year. Comparison students received no
      researcher-provided intervention (n = 42). The researchers used multigroup
      modeling with nested comparisons to evaluate the statistical significance of Time
      3 estimates. Students in both treatments outperformed the comparison students on
      assessments of decoding, fluency, and comprehension. Intervention type did not
      moderate the pattern of effects, although students in the standardized treatment
      had a small advantage over individualized students on word attack. This study
      provides a framework from which to refine further interventions for older
      students with reading disabilities.

PMID- 23125461
TI  - A multi-centre clinico-genetic analysis of the VPS35 gene in Parkinson disease
      indicates reduced penetrance for disease-associated variants.
AB  - BACKGROUND: Two recent studies identified a mutation (p.Asp620Asn) in the
      vacuolar protein sorting 35 gene as a cause for an autosomal dominant form of
      Parkinson disease . Although additional missense variants were described, their
      pathogenic role yet remains inconclusive. METHODS AND RESULTS: We performed the
      largest multi-center study to ascertain the frequency and pathogenicity of the
      reported vacuolar protein sorting 35 gene variants in more than 15,000
      individuals worldwide. p.Asp620Asn was detected in 5 familial and 2 sporadic PD
      cases and not in healthy controls, p.Leu774Met in 6 cases and 1 control,
      p.Gly51Ser in 3 cases and 2 controls. Overall analyses did not reveal any
      significant increased risk for p.Leu774Met and p.Gly51Ser in our cohort.
      CONCLUSIONS: Our study apart from identifying the p.Asp620Asn variant in familial
      cases also identified it in idiopathic Parkinson disease cases, and thus provides
      genetic evidence for a role of p.Asp620Asn in Parkinson disease in different
      populations worldwide.

PMID- 23125464
TI  - Stress relaxation via addition-fragmentation chain transfer in high T(g), high
      conversion methacrylate-based systems.
AB  - To reduce shrinkage stress which arises during the polymerization of crosslinked
      polymers, allyl sulfide functional groups were incorporated into methacrylate
      polymerizations to determine their effect on stress relaxation via addition
      fragmentation chain transfer (AFCT). Additionally, stoichiometrically balanced
      thiol and allyl sulfide-containing norbornene monomers were incorporated into the
      methacrylate resin to maximize the overall functional group conversion and
      promote AFCT while also enhancing the polymer's mechanical properties. Shrinkage
      stress and reaction kinetics for each of the various functional groups were
      measured by tensometry and Fourier-transform infrared (FTIR) spectroscopy,
      respectively. The glass transition temperature (T(g)) and elastic moduli (E')
      were measured using dynamic mechanical analysis. When the allyl sulfide
      functional group was incorporated into dimethacrylates, the polymerization
      induced shrinkage stress was not relieved as compared with analogous propyl
      sulfide-containing resins. These analogous propyl sulfide containing monomers are
      incapable of undergoing AFCT while having similar chemical structure and
      crosslink density to the allyl sulfide containing methacrylates. Here, a
      monomethacrylate monomer that also contains a cyclic allyl sulfide (PAS) was
      found to increase the crosslinking density nearly 20 times as compared to an
      analogous monomethacrylate in which the allyl sulfide was replaced with an ethyl
      sulfide. Despite the much higher crosslink density, the PAS formulation exhibited
      no concomitant increase in stress. Thiol-norbornene resins were copolymerized in
      PAS to promote AFCT as well as to synergistically combine the ring opening
      benefits associated with the thiol-ene reaction. AFCT resulted in a 63% reduction
      of polymerization stress and a 45 degrees C enhancement of the glass transition
      temperature in the allyl sulfide-containing thiol-norbornene-methacrylate system
      compared with rubbery dimethacrylates. When compared with conventional glassy
      dimethacrylates, this combined system has less than 10% of the typical shrinkage
      stress level while having similarly excellent mechanical properties.

PMID- 23125465
TI  - Soil metaproteomics - Comparative evaluation of protein extraction protocols.
AB  - Metaproteomics and its potential applications are very promising to study
      microbial activity in environmental samples and to obtain a deeper understanding
      of microbial interactions. However, due to the complexity of soil samples the
      exhaustive extraction of proteins is a major challenge. We compared soil protein
      extraction protocols in terms of their protein extraction efficiency for two
      different soil types. Four different protein extraction procedures were applied
      based on (a) SDS extraction without phenol, (b) NaOH and subsequent phenol
      extraction, (c) SDS-phenol extraction and (d) SDS-phenol extraction with prior
      washing steps. To assess the suitability of these methods for the functional
      analysis of the soil metaproteome, they were applied to a potting soil high in
      organic matter and a forest soil. Proteins were analyzed by two-dimensional
      liquid chromatography/tandem mass spectrometry (2D-LC-MS/MS) and the number of
      unique spectra as well as the number of assigned proteins for each of the
      respective protocols was compared. In both soil types, extraction with SDS-phenol
      (c) resulted in "high" numbers of proteins. Moreover, a spiking experiment was
      conducted to evaluate protein recovery. To this end sterilized forest soil was
      amended with proteins from pure cultures of Pectobacterium carotovorum and
      Aspergillus nidulans. The protein recovery in the spiking experiment was almost
      50%. Our study demonstrates that a critical evaluation of the extraction protocol
      is crucial for the quality of the metaproteomics data, especially in highly
      complex samples like natural soils.

PMID- 23125466
TI  - Functionalized Cyclopropenes and Methylenecyclopropenes from Dianions of 3
      Hydroxymethylcyclopropenes.
AB  - 1,2-Disubstituted-3-hydroxymethylcyclopropene derivatives have been synthesized
      by reacting the dianions of 1-alkyl-3-hydroxymethylcyclopropenes with a range of
      electrophiles. Additionally, a complementary procedure is described for one-pot
      sequential alkylation/rearrangement to provide a convenient synthesis of a chiral
      methylenecyclopropane directly from a 1-alkyl-3-hydroxymethylcyclopropene.

PMID- 23125467
TI  - New methodology for the preparation of 3-hydroxy-2-pyridinone (3,2-HOPO)
      chelators - Reaction of amines with a novel electrophilic 3,2-HOPO precursor.
AB  - The preparation of the new electrophilic iminium ester mesylate salt 5 and its
      reaction with primary and secondary amines have been investigated. Aniline, t
      butylamine, and secondary amines react with 5 via ring opening to give the
      corresponding HOPO derivatives in high yields. The usefulness of this methodology
      has been demonstrated by the preparation of two new di-HOPO derivatives 19 and
      21. This method allows the introduction of the HOPO ligand onto a variety of
      amine platforms without the concomitant formation of an amide bond and provides
      access to HOPO chelators of increased water solubility.

PMID- 23125468
TI  - Surface Modification of Poly(amidoamine) (PAMAM) Dendrimer as Antimicrobial
      Agents.
AB  - Poly(amidoamine) (PAMAM) (G3) dendrimer was modified into quaternary ammonium
      salts using tertiary amines with different chain lengths: dimethyldodecyl amine,
      dimethylhexyl amine, and dimethylbutyl amine using an efficient synthetic route.
      The antimicrobial activity of these dendrimer ammonium salts against
      Staphylococcus and E-coli bacteria was examined using the disc diffusion method.
      It was found that quaternary ammonium salt prepared with the dimethyldodecyl
      amine exhibits antimicrobial efficacy against Staphalococus and E.coli bacteria.

PMID- 23125469
TI  - Image Generation in Individuals with Generalized Social Phobia.
AB  - Individuals with social phobia report experiencing recurrent negative images of
      themselves in social situations. However, research on the role of visual imagery
      in social phobia has relied exclusively on self-report measures. In the first
      study, we used a visual image generation task with social-threat and neutral
      stimuli to test the hypothesis that individuals with Generalized Social Phobia
      (GSP, n = 32) are more efficient at generating images related to social-threat
      words than are non-anxious-controls (NACs, n = 28). We found that, contrary to
      our hypothesis, the GSP and NAC groups did not differ in speed of generating
      images related to social-threat words. However, the GSP group was significantly
      slower than the NAC group at generating images related to neutral words. To
      further examine the generation of neutral images, we conducted a second study
      using a well-validated neutral image generation task, and found that the GSP
      group (n = 24) was slower to generate neutral images than were the NAC (n = 21)
      and anxious-control (AC, n = 15) groups, which did not differ from each other.
      Taken together, findings from the two studies suggest that social phobia is
      characterized by less efficient generation of neutral images.

PMID- 23125470
TI  - Recursively Imputed Survival Trees.
AB  - We propose recursively imputed survival tree (RIST) regression for right-censored
      data. This new nonparametric regression procedure uses a novel recursive
      imputation approach combined with extremely randomized trees that allows
      significantly better use of censored data than previous tree based methods,
      yielding improved model fit and reduced prediction error. The proposed method can
      also be viewed as a type of Monte Carlo EM algorithm which generates extra
      diversity in the tree-based fitting process. Simulation studies and data analyses
      demonstrate the superior performance of RIST compared to previous methods.

PMID- 23125471
TI  - Posterior Reversible Encephalopathy Syndrome Presenting as Opsoclonus-Myoclonus.
AB  - Opsoclonus-myoclonus may be caused by various neurological conditions and toxic
      metabolic states, but typically occurs as a parainfectious or paraneoplastic
      manifestation. The development of opsoclonus-myo-clonus has been variably
      attributed to lesions in the pons or cerebellum. Herein the authors describe a
      case of opsoclonus-myoclonus due to posterior reversible encephalopathy syndrome
      in which magnetic resonance imaging revealed lesions in the region of the
      cerebellar dentate nuclei. Clinical and radiological resolution of the opsoclonus
      myoclonus and of the posterior reversible encephalopathy syndrome followed
      antihyperten-sive therapy.

PMID- 23125472
TI  - Parenting Stress, Social Support, and Mother-Child Interactions in Families of
      Multiple and Singleton Preterm Toddlers.
AB  - The study investigated family support as a buffer of stress in 153 mothers and
      preterm toddlers. Data were collected regarding maternal depressive symptoms,
      parenting stress, and family support; infant health; and videotaped mother-child
      interactions. Although more parenting stress related to less optimal child play,
      only information support functioned as a protective factor. Information support
      predicted positive play under high, but not low, maternal stress. Mothers of
      multiples reported more parenting stress than mothers of singletons.

PMID- 23125473
TI  - THE EFFECT OF PREGNANCY AND POSTPARTUM RECOVERY ON THE VISCOELASTIC BEHAVIOR OF
      THE RAT CERVIX.
AB  - The objective of this study was to elucidate the normal functional adaptations of
      the cervix in pregnancy. Utilizing a Long-Evans rodent model, the cervix was
      divided into distal and proximal portions for virgin, mid-pregnant, and four
      weeks postpartum animals. The quasi-linear viscoelastic theory describes the
      elastic and viscous behavior of the cervix. A hydroxyproline assay was used to
      measure collagen content. The nonlinearity of the elastic response significantly
      increased throughout the entire cervix during pregnancy when compared to virgin
      samples (p < 0.05) and was similar to virgin samples postpartum. All viscous
      behavior, except for the short-term relaxation of the proximal cervix,
      significantly differed for pregnant specimens (p < 0.05) and remained similar to
      pregnant samples postpartum. Collagen content was found to increase by mid
      pregnancy only in the proximal cervix when compared to virgin. Distal and
      proximal portions, however, were found to differ in collagen content at all time
      points (p < 0.05). This study finds that the cervix becomes elastically stiffer
      with increasing strain and exhibits increased viscous behavior during pregnancy,
      with incomplete recovery postpartum. These alterations allow for quick
      dissipation of loads, and are likely related to altered matrix organization and
      porosity reported by others.

PMID- 23125474
TI  - Lexical diversity for adults with and without aphasia across discourse
      elicitation tasks.
AB  - BACKGROUND: Differences in lexical diversity (LD) across different discourse
      elicitation tasks have been found in neurologically intact adults (NIA)
      (Fergadiotis, Wright, & Capilouto, 2010) but have not been investigated
      systematically in people with aphasia (PWA). Measuring lexical diversity in PWA
      may serve as a useful clinical tool for evaluating the impact of word retrieval
      difficulties at the discourse level.  AIMS: The study aims were (a) to explore
      the differences between the oral language samples of PWA and NIA in terms of LD
      as measured by dedicated computer software (voc-D), (b) to determine whether PWA
      are sensitive to discourse elicitation task in terms of LD, and (c) to identify
      whether differences between PWA and NIA vary in magnitude as a function of
      discourse task.  METHOD #ENTITYSTARTX00026; PROCEDURES: Oral language samples
      from 25 PWA and 27 NIA were analysed. Participants completed three commonly used
      discourse elicitation tasks (single pictures, sequential pictures, story telling)
      and voc-D was used to obtain estimates of their LD.  OUTCOMES #ENTITYSTARTX00026;
      RESULTS: A mixed 2 * 3 ANOVA revealed a significant group task interaction that
      was followed by an investigation of simple main effects and tetrad*comparisons.
      Different patterns of LD were uncovered for each group. For the NIA group results
      were consistent with previous findings in the literature according to which LD
      varies as a function of elicitation technique. However, for PWA sequential
      pictures and story telling elicited comparable estimates of LD.  CONCLUSIONS:
      Results indicated that LD is one of the microlinguistic indices that are
      influenced by elicitation task and the presence of aphasia. These findings have
      important implications for modelling lexical diversity and selecting and
      interpreting results from different discourse elicitation tasks.

PMID- 23125475
TI  - Cognitive Correlates of Inadequate Response to Reading Intervention.
AB  - The cognitive attributes of Grade 1 students who responded adequately and
      inadequately to a Tier 2 reading intervention were evaluated. The groups included
      inadequate responders based on decoding and fluency criteria (n = 29), only
      fluency criteria (n = 75), adequate responders (n = 85), and typically achieving
      students (n = 69). The cognitive measures included assessments of phonological
      awareness, rapid letter naming, oral language skills, processing speed,
      vocabulary, and nonverbal problem solving. Comparisons of all four groups
      identified phonological awareness as the most significant contributor to group
      differentiation. Measures of rapid letter naming, syntactic comprehension/working
      memory, and vocabulary also contributed uniquely to some comparisons of adequate
      and inadequate responders. In a series of regression analyses designed to
      evaluate the contributions of responder status to cognitive skills independently
      of variability in reading skills, only the model for rapid letter naming achieved
      statistical significance, accounting for a small (1%) increment in explained
      variance beyond that explained by models based only on reading levels.
      Altogether, these results do not suggest qualitative differences among the
      groups, but are consistent with a continuum of severity associated with the level
      of reading skills across the four groups.

PMID- 23125476
TI  - Statistical Model for Biochemical Network Inference.
AB  - We describe a statistical method for predicting most likely reactions in a
      biochemical reaction network from the longitudinal data on species
      concentrations. Such data is relatively easily available in biochemical
      laboratories, for instance, via the popular RT-PCR technology. Under the assumed
      kinetics of the law of mass action, we also propose the data-based algorithms for
      estimating the prediction errors and for network dimension reduction. The second
      algorithm allows in particular for the application of the original algebraic
      inferential procedure described in [4] without the unnecessary restrictions on
      the dimension of the network stoichiometric space. Simulated examples of
      biochemical networks are analyzed, in order to assess the proposed methods'
      performance.

PMID- 23125477
TI  - Predicting Route Choices of Drivers Given Categorical and Numerical Information
      on Delays Ahead: Effects of Age, Experience, and Prior Knowledge.
AB  - In recent years there has been a considerable increase in the systems used to
      provide real-time traffic information to motorists. Examples of such systems
      include dynamic message signs and 511 travel information systems. However, such
      systems can be used to reduce congestion-one of their primary purposes-only if
      one can predict the route choices of drivers as a function of the information
      displayed. This simulator study looks at the diversion pattern that occurs when
      delays are reported ahead on the main route and how these diversion patterns vary
      as a function of delay times (for numerical delay signs), message content (for
      categorical delay signs), use of 511, and drivers' familiarity with the
      alternative route travel times across two different age groups. For numerical
      delay signs, the study shows that one can reliably predict the diversion
      frequencies at the different delays and across the different ages; then it is
      possible for traffic engineers to know ahead of time how likely it is for drivers
      to take an alternative route. For categorical delay signs, the findings indicate
      that drivers' knowledge of the alternative route travel time affects the choices
      of older versus younger or middle-aged adults differently. When the times are not
      known, the two groups behave differently; when the times are known, the groups
      behave similarly. This finding suggests that traffic engineers should try where
      possible to present the alternative route travel times as well as the delays on
      the main route.

PMID- 23125478
TI  - Changes in Marital and Partner Relationships in the Aftermath of Hurricane
      Katrina: An Analysis With Low-Income Women.
AB  - Little is known about the impact of natural disasters on marital and partner
      relationships. In this study, the authors aimed to fill this gap by investigating
      the changes in such relationships in a sample of 40 low-income, mostly African
      American women who survived Hurricane Katrina. Through in-depth interviews,
      participants described how the hurricane affected their intimate relationships.
      The authors found that, although many participants reported negative changes in
      their relationships, others reported that their relationships grew stronger,
      often despite initial strain. As a framework for understanding the processes
      underlying participants' negative and positive outcomes, the authors drew on the
      family stress model. Consistent with the model, participants reported that the
      hurricane led to external stressors, including unemployment and prolonged
      separations, and that these stressors, in turn, undermined both individual
      functioning and relational processes (e.g., communication and support).
      Conversely, participants reporting positive changes experienced new employment
      opportunities, a greater sense of perspective, and high levels of effective
      communication and support in their relationships. Based on the findings, policies
      that reduce the economic strain of low-income families in the aftermath of
      disasters and empirically supported, culturally sensitive, clinical interventions
      for individuals and couples are recommended.

PMID- 23125479
TI  - High Performance Multiple Sequence Alignment System for Pyrosequencing Reads from
      Multiple Reference Genomes.
AB  - Genome resequencing with short reads generated from pyrosequencing generally
      relies on mapping the short reads against a single reference genome. However,
      mapping of reads from multiple reference genomes is not possible using a pairwise
      mapping algorithm. In order to align the reads w.r.t each other and the reference
      genomes, existing multiple sequence alignment(MSA) methods cannot be used because
      they do not take into account the position of these short reads with respect to
      the genome, and are highly inefficient for large number of sequences. In this
      paper, we develop a highly scalable parallel algorithm based on domain
      decomposition, referred to as P-Pyro-Align, to align such large number of reads
      from single or multiple reference genomes. The proposed alignment algorithm
      accurately aligns the erroneous reads, and has been implemented on a cluster of
      workstations using MPI library. Experimental results for different problem sizes
      are analyzed in terms of execution time, quality of the alignments, and the
      ability of the algorithm to handle reads from multiple haplotypes. We report high
      quality multiple alignment of up to 0.5 million reads. The algorithm is shown to
      be highly scalable and exhibits super-linear speedups with increasing number of
      processors.

PMID- 23125480
TI  - Identifying Feasible Design Concepts for Products with Competing Performance
      Requirements by Metamodeling of Loss-Scaled Principal Components.
AB  - Engineering design often involves the determination of design variable settings
      to optimize competing performance requirements. In the early design stages we
      propose narrowing down the domain of design solutions using metamodels of
      principal components of the multiple performance levels that have been scaled by
      a multivariate quadratic loss function. The multivariate quadratic loss function
      is often used as the objective function in reaching optimal solutions because it
      utilizes the correlation structure of the design's performance metrics and
      penalizes off-target performance in a symmetrical manner. We also compare the
      computational performance of these loss-scaled principal components when used to
      solve for the design with minimal expected multivariate quadratic loss under
      three modeling approaches: response surface methodology, multivariate adaptive
      regression splines, and spatial point modeling. We demonstrate the technique on
      the design of the mechanical frame of an electric vehicle with six desired
      performance levels determined simultaneously by the dimensions of eight
      mechanical design elements. The method is the focus in this work.

PMID- 23125481
TI  - Biomass productivity and productivity of fatty acids and amino acids of
      microalgae strains as key characteristics of suitability for biodiesel
      production.
AB  - Microalgae are discussed as an alternative source for the production of biofuels.
      The lipid content compared to cultivation time of used species is the main reason
      for any choice of a special strain. This paper reviews more analytical data of 38
      screened microalgae strains. After the cultivation period, total content of
      lipids was analysed. The extracted fatty acids were quantified as fatty acid
      methyl esters by GC analysis. The amino acids were analysed by HPLC. Chlorella
      sp., Chlorella saccharophila, Chlorella minutissima and Chlorella vulgaris were
      identified as species with the highest productivity of fatty acids relevant to
      transesterification reactions. The components were mainly linoleic acid, palmitic
      acid and oleic acid. To increase productivity of highly saturated fatty acids,
      cultivation parameters light intensity and temperature were varied. In this
      manner, the ideal conditions for biodiesel production were defined in this
      publication. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this
      article (doi:10.1007/s10811-012-9795-3) contains supplementary material, which is
      available to authorized users.

PMID- 23125482
TI  - Synthesis of Farnesol Analogues Containing Triazoles in Place of Isoprenes
      through 'Click Chemistry'
AB  - A solid-phase three-component Huisgen reaction has been used to generate polar
      farnesol and farnesyl diphosphate analogues. The Cu(I)-catalyzed 1,3
      cycloadditions of various azides with solid supported (E)-3-methylhept-2-en-6-yn
      1-ol provided only the 1,4-disubstituted 1,2,3-triazole regioisomers. The organic
      azides were generated in situ to minimize handling of potentially explosive
      azides. We have employed this powerful 'click chemistry' to make farnesol
      analogues where both beta- and gamma-isoprenes were replaced by triazole and
      substituted aromatic rings, respectively.

PMID- 23125483
TI  - New ratiometric optical oxygen and pH dual sensors with three emission colors for
      measuring photosynthetic activity in Cyanobacteria.
AB  - Photosynthetic algae and cyanobacteria have been proposed for producing biofuels
      through a direct photoconversion process. To accelerate the efforts of
      discovering and screening microbes for biofuel production, sensitive and high
      throughput methods to measure photosynthetic activity need to be developed. Here
      we report the development of new ratiometric optical oxygen and pH dual sensors
      with three emission colors for measuring photosynthetic activities directly. The
      dual sensor system can measure oxygen (O(2)) generation and pH increase resulted
      from carbon dioxide (CO(2)) consumption simultaneously. The sensor was prepared
      by a copolymerization of three monomeric probes, an intra-reference probe (IRP)
      which does not respond to pH or O(2), a probe for pH sensing (pHS), and an O(2)
      probe for O(2) sensing (OS) with 2-hydroxyethyl methacrylate (HEMA) and
      acrylamide (AM). After polymerization, the three probes were chemically
      immobilized in an ion and O(2) permeable poly(2-hydroxyethyl methacrylate)-co
      polyacrylamide (PHEMA-co-PAM) matrix. The resulted sensing films (membranes)
      exhibited three emission colors with well separated emission spectra, covering
      blue, green, and red emission windows, under 380 nm light excitation. Responses
      of the sensors to pH and dissolved O(2) were investigated in buffers and
      cyanobacterial cell cultures (Synechocystis sp. PCC 6803). In spite of the strong
      autofluorescence from cyanobacteria, the sensors were able to determine the pH
      values and dissolved O(2) concentrations accurately and reproducibly. The
      measured results using the optical sensors were well in accordance with
      measurements using electrodes with minimal experimental variations. The sensors
      were further applied for evaluation of photosynthetic activities of Synechocystis
      sp. PCC 6803 at the exponential and stationary phases. The results were
      consistent with biological observation that the photosynthetic activity in the
      exponential phase was higher than that in the stationary phase.

PMID- 23125484
TI  - Value of C-reactive protein as a risk factor for acute coronary syndrome: a
      comparison with apolipoprotein concentrations and lipid profile.
AB  - OBJECTIVE: To investigate whether assessment of C-reactive protein (CRP) and
      apolipoproteins, besides the traditional lipid profile, enhances the assessment
      process for the risk of acute coronary syndrome (ACS). METHODS: The study group
      consisted of 220 consecutive patients admitted to hospital within the first 6
      hours from the onset of chest pain. Patients were diagnosed with unstable angina
      (n = 96), non-ST-elevation myocardial infarction (NSTEMI; n = 57), or ST
      elevation myocardial infarction (STEMI; n = 67). ACS patients were compared with
      116 healthy volunteers in a case-control study. The serum was assayed on
      admission for CRP, apolipoproteins ApoAI and ApoB100, and lipid parameters.
      RESULTS: The highest concentrations of CRP were found in NSTEMI and STEMI, with a
      median value four-fold higher in ACS patients than in controls (P < 0.0001). Only
      CRP significantly increased the probability of ACS development (adjusted odds
      ratio for a 1 mg/L increase 1.90; 95% confidence interval [CI] 1.34-2.89) and
      explained 90% of the variation for ACS development. Similarly, we demonstrated
      the highest diagnostic accuracy for CRP among all investigated markers (area
      under the curve 0.80; 95% CI 0.75-0.85). CONCLUSIONS: Our study indicates that
      CRP superiorly to apolipoproteins and lipid profile facilitates the risk
      stratification for ACS occurrence.

PMID- 23125485
TI  - Atherosclerosis in rheumatoid arthritis.

PMID- 23125488
TI  - 'Only fixation' as rationale treatment for spinal canal stenosis.

PMID- 23125486
TI  - Altered AKT1 and MAPK1 gene expression on peripheral blood mononuclear cells and
      correlation with T-helper-transcription factors in systemic lupus erythematosus
      patients.
AB  - Kinases have been implicated in the immunopathological mechanisms of Systemic
      Lupus Erythematosus (SLE). v-akt murine-thymoma viral-oncogene-homolog 1 (AKT1)
      and mitogen-activated-protein-kinase 1 (MAPK1) gene expressions in peripheral
      mononuclear cells from thirteen SLE patients with inactive or mild disease were
      evaluated using quantitative real-time reverse-transcription polymerase-chain
      reaction and analyzed whether there was any correlation with T-helper (Th)
      transcription factors (TF) gene expression, cytokines, and S100A8/S100A9
      (Calprotectin). Age- and gender-matched thirteen healthy controls were examined.
      AKT1 and MAPK1 expressions were upregulated in SLE patients and correlated with
      Th17-(Retinoic acid-related orphan receptor (ROR)-C), T-regulatory-(Treg)
      (Transforming Growth Factor Beta (TGFB)-2), and Th2-(interleukin (IL)-5)-related
      genes. MAPK1 expression correlated with Th1-(IL-12A, T-box TF-(T-bet)), Th2-(GATA
      binding protein-(GATA)-3), and IL-10 expressions. IL-10 expression was increased
      and correlated with plasma Tumor Necrosis Factor (TNF)-alpha and Th0-(IL-2), Th1
      (IL-12A, T-bet), GATA3, Treg-(Forkhead/winged-helix transcription factor- (FOXP)
      3), and IL-6 expressions. FOXP3 expression, FOXP3/RORC, and FOXP3/GATA3
      expression ratios were increased. Plasma IL-1beta, IL-12(p70), Interferon-(IFN)
      gamma, and IL-6 cytokines were augmented. Plasma IL-1beta, IL-6, IL-2, IFN-gamma,
      TNF-alpha, IL-10, and IL-13 correlated with C-reactive protein, respectively.
      Increased Calprotectin correlated with neutrophils. Conclusion, SLE patients
      presented a systemic immunoinflammatory activity, augmented AKT1 and MAPK1
      expressions, proinflammatory cytokines, and Calprotectin, together with increased
      expression of Treg-related genes, suggesting a regulatory feedback opposing the
      inflammatory activity.

PMID- 23125487
TI  - A Picrorhiza kurroa derivative, picroliv, attenuates the development of dextran
      sulfate-sodium-induced colitis in mice.
AB  - BACKGROUND: Free radicals and proinflammatory cytokines have been shown to play a
      critical role in the pathogenesis of ulcerative colitis (UC). Picroliv, a
      Picrorhiza kurroa derivative, has been demonstrated to have antioxidant and anti
      inflammatory effect. The purpose of the study was to investigate the effects of
      picroliv on experimental model of UC in mice. MATERIALS AND METHODS: Picroliv was
      administrated orally by gavage to mice with colitis induced by dextran sulfate
      sodium (DSS). Disease activity index (DAI), colon length, and histology score
      were observed. Myeloperoxidase (MPO) activity, and SOD, MDA concentrations were
      measured by enzyme-linked immunosorbent assay (ELISA) while the expression of
      cytokine mRNAs was studied by real-time-quantitative polymerase chain reaction
      and also ELISA. The expression of NF-kappaB p65 was observed by
      immunohistochemistry staining and western blotting. RESULTS: A significant
      improvement was observed in DAI and histological score in mice treated with
      picroliv, and incerased MPO activity, MDA concentrations, and the expression of
      IL-1beta, TNF-alpha, and NF-kappaB p65 in mice with DSS-induced colitis were
      significantly reduced while decreased SOD level increased following
      administration of picroliv. CONCLUSION: The administration of picroliv leads to
      an amelioration of DSS-induced colitis, suggesting administration of picroliv may
      provide a therapeutic approach for UC.

PMID- 23125489
TI  - Penetrating spinal injuries and their management.
AB  - Penetrating spinal trauma due to missile/gunshot injuries has been well reported
      in the literature and has remained the domain of military warfare more often.
      Civic society's recent upsurge in gunshot injuries has created a dilemma for the
      treating neurosurgeon in many ways as their management has always involved
      certain debatable and controversial issues. Both conservative and surgical
      management of penetrating spinal injuries (PSI) have been practiced widely. The
      chief neurosurgical concern in these types of firearm injuries is the degree of
      damage sustained during the bullet traversing through the neural tissue and the
      after-effects of the same in long term. We had an interesting case of a
      penetrating bullet injury to cervical spine at C2 vertebral level. He was
      operated and the bullets were removed from posterior midline approach. Usually,
      the management of such cases differs from region to region depending on the
      preference of the surgeon but still certain common principles are followed world
      over. Thus, we realized the need to review the literature regarding spinal
      injuries with special emphasis on PSI and to study the recent guidelines for
      their treatment in light of our case.

PMID- 23125490
TI  - Significant relationship between local angle at fused segments and C2-7 angle:
      Average duration of longer than 20 years after anterior cervical discectomy and
      fusion.
AB  - BACKGROUND: The authors have focused their attention to the radiological
      durability of cervical sagittal alignment after anterior cervical discectomy and
      fusion (ACDF) using autologous bone grafting. MATERIALS AND METHODS: Among the
      patients who underwent ACDF with trans-unco-discal (TUD) approach between 1976
      and 1997, 22 patients (16 males and 6 females) made return visits for a clinical
      evaluation. Patients with trauma or previously treated by anterior cervical
      fusion or by posterior decompression were excluded from the present study.
      Clinical evaluation included adjacent segment degeneration (ASD), osseous fusion,
      local angle at the fused segments and C2-7 angle of cervical spine. RESULTS: The
      duration after ACDF ranged from 13 to 34 years with an average of 21.3 +/- 7.0
      years. A single level fusion was done on 8 patients, 2 levels on 11 patients, 3
      levels on 2 patients, and 4 levels on 1 patient. Imaging studies indicated that
      12 of the 22 patients (54.5%) were graded as having symptomatic ASD. Osseous bony
      fusion at ACDF was recognized in all cases. None of the patients demonstrated
      kyphotic malalignment of the cervical spine. Average degrees of local angle at
      the fused segments and the C2-7 angle were 7.06 and 17.6, respectively.
      Statistical analysis indicated a significant relationship between the local at
      the fused segments and C2-7 angles. CONCLUSIONS: Sagittal alignment of the
      cervical spine was durable long after ACDF when the local angle at the fused
      segments was well stabilized.

PMID- 23125491
TI  - Evaluation of the subaxial injury classification system.
AB  - STUDY DESIGN: Retrospective clinical study of patients treated for subaxial
      cervical spine trauma (SCST) at a tertiary medical center. PURPOSE: Evaluate the
      validity of the Subaxial Injury Classification (SLIC) system in surgical versus
      non-surgical decision making for SCST. INCLUSION CRITERIA: Age >12 years,
      presence of SCST with complete clinical and radiological (CT and MRI) data.
      EXCLUSION CRITERIA: Patients with incomplete radiographic or clinical data,
      pathological fractures, isolated upper cervical trauma (occiput to C2), isolated
      transverse process or spinous process fractures, chronic or age indeterminate
      fractures, isolate MRI findings, and severe systemic trauma with death prior to
      either surgical or non-surgical treatment. RESULTS: Fourteen patients were
      treated non-surgically (C), whereas 24 were treated surgically (S). In the C
      group, the SLIC score ranged from 0 to 5 points (standard deviation [SD] = 1.20
      points; mean 1.07; median 1). Just 1 patient had an SLIC score greater than 2
      (7.1% of the patients). In the S group, the SLIC score ranged from 1 to 10 points
      (standard deviation [SD] = 2.03 points; mean 5.6; median 6). Just 2 patients had
      an SLIC score smaller than 4 (both with 1 point each, 8.3% of the total group).
      All the other 22 (accounting for 91.6%) patients had an SLIC of 4 or more points.
      CONCLUSIONS: Our study suggests that the SLIC classification looks to be a
      promising system to aid spinal surgeons in the decision-making process of
      subaxial cervical trauma, but a large prospective cohort study is required.

PMID- 23125492
TI  - Cervical vertebrae anomalies in patients with class III skeletal malocclusion.
AB  - BACKGROUND AND OBJECTIVE: Studies have documented that deviations in skeletal
      components such as the cranial base, the mid-facial complex and the mandible may
      be associated with morphological factors in patients with class III skeletal
      malocclusion. Furthermore, deviations in head and neck posture may be associated
      with the class III skeletal malocclusion. The purpose of this study was to
      compare cervical vertebrae morphology in patients with class III skeletal
      malocclusion and adults with normal occlusion. MATERIALS AND METHODS: This case
      control study assessed 30 patients with class III skeletal malocclusion (aged 17
      30 yrs, with normal vertical growth pattern and ANB<0) were compared with 46
      controls (aged 17-30 years, with normal vertical growth pattern, ANB=3+1).
      Cervical vertebrae anomalies (fusion anomalies and posterior arch deficiency)
      were assessed via evaluation of their lateral cephalograms. The t- test and
      Fisher's exact test were used for statistical analysis. RESULTS: In the study
      group, 73.3% had fusion of the body of the cervical vertebrae, while in the
      control group only 32.6% showed fusion. The fusion in the control group was
      between C2 and C3 in all cases; whereas, in the study group, fusion was seen
      between C2-C3, C3-C!4 or C4-C!5. Additionally, cervical column deviations
      occurred significantly more often in the study group compared to the control
      group (P<0.001). CONCLUSION: Class III skeletal malocclusion may be associated
      with fusion of cervical vertebrae and deviation of the cervical column.

PMID- 23125493
TI  - Normal variation of diffusion tensor parameters of the spinal cord in healthy
      subjects at 3.0-Tesla.
AB  - AIMS: The purposes of the present study were to clarify the normal variation and
      to determine the normal reference values of diffusion tensor (DT) parameters
      (mean diffusivity [MD] and fractional anisotropy [FA]) of the spinal cord in
      single-shot fast spin-echo-based sequence at 3.0-Tesla (3T). MATERIALS AND
      METHODS: Thirty healthy subjects (mean age = 44.2 years, range = 20-72 years)
      were enrolled for this study. Mean values of MD and FA in six spinal levels
      (C2/3, C3/4, C4/5, C5/6, C6/7, and C7/Th1) were measured. Mean values, variances,
      and distributions of the MD and FA in each spinal level were analyzed. Age
      dependent change of MD and FA as well as correlation between MD and FA was also
      analyzed. RESULTS: At all spinal levels, the values can be considered to be
      Gaussian distribution in MD but not in FA. A significant statistical negative
      correlation was observed between aging and the values of MD (r = 0.429, P =
      0.018), but insignificant between the values of FA (P = 0.234). A slight
      significant statistical negative correlation was observed between the values of
      MD and FA (r = 0.156, P = 0.037). One way repeated measures analysis of variance
      indicated the significant difference between the spinal levels in both MD (P =
      0.003) and FA (P < 0.0001). CONCLUSIONS: The analyzed data in the present study
      would be helpful for comparison when investigating the spinal condition of spinal
      disorders.

PMID- 23125494
TI  - Activ C cervical disc replacement for myelopathy.
AB  - BACKGROUND: Cervical disc replacement is becoming an increasingly popular
      treatment option for cervical myelopathy. It retains motion at the affected
      segment, unlike anterior cervical discectomy and fusion. The aim of this study is
      to assess the outcomes of a series of patients who underwent Activ C disc
      replacement for cervical myelopathy. MATERIALS AND METHODS: A series of patients
      at the above Trust with clinical and radiological evidence of cervical myelopathy
      who were suitable for cervical disc replacement from 2007 to 2009 were included.
      Implants were inserted by one of two consultant surgeons {IMS, MO'M}. Patients
      were assessed preoperatively and at six, 12 and 24 months, postoperatively, with
      a visual analogue score (VAS) for neck and arm pain severity and frequency, the
      Neck Disability Index questionnaire (NDI) and the Centre for Epidemiologic
      Studies Depression questionnaire (CES-D). RESULTS: Ten patients underwent surgery
      between May 2007 and July 2009, 6 women, and 4 men. Average age was 54 years (40
      64). Disc levels replaced were: four at C4-5; eight at C5-6; seven at C6-7. Three
      patients had one disc replaced, five patients had two discs replaced, and two
      patients had three discs replaced. The VAS for neck pain improved from 5.9 pre
      operatively to 1.4-24 months postoperatively and the VAS arm pain improved from
      5.4 to 2.6. The NDI improved from 51% preoperatively to 26.8% at 24 months
      postoperatively. The CES-D showed a slight increase from 19.5 preoperatively to
      21.7 at 24 months, postoperatively. CONCLUSION: Cervical decompression and disc
      replacement improves pain and function in patients with cervical myelopathy. This
      benefit is maintained at 24 months post op, with no cases requiring revision.

PMID- 23125495
TI  - An interesting clinical association of short neck with an unusual laryngeal
      anomaly.
AB  - An elongated high-rising epiglottis can represent a normal variation of the
      larynx in a majority of pediatric patients. However, there are virtually no
      reports available for visible or high-rising epiglottis on routine oral
      examination in adult patients without upper respiratory tract inflammation. We
      report an unusual case with prominently visible epiglottis on oral examination.
      We diagnosed him with a rare congenital disorder based on associated physical
      examination and imaging evidence of short neck, low hair line, Sprengel's
      anomaly, left digital hypoplasia, restricted neck movements, cervical vertebra
      fusion, and mirror movements (synkinesia).

PMID- 23125496
TI  - One-stage surgery through posterior approach-for L5-S1 spondyloptosis.
AB  - Grade 5 spondylolisthesis or spondyloptosis is a rare condition. Generally, the
      surgical management of spondyloptosis includes multi-staged procedures instead of
      one-staged procedures. One-stage treatment for spondyloptosis is very rare. A 15
      year-old girl with L5-S1 spondyloptosis was admitted with severe low back pain.
      There was no history of trauma. The patient underwent L5 laminectomy, L5-S1
      discectomy, resection of sacral dome, reduction, L3-L4-L5-S1 pedicular screw
      fixation, and interbody-posterolateral fusion through the posterior approach. The
      reduction was maintained with bilateral L5-S1 discectomy, resection of the sacral
      dome, and transpedicular instrumentation from L3 to S1. In this particular case,
      one-staged approach was adequate for the treatment of L5-S1 spondyloptosis. One
      staged surgery using the posterior approach may be adequate for the treatment of
      L5-S1 spondyloptosis while avoiding the risks inherent in anterior approaches.

PMID- 23125497
TI  - Langerhans' cell histiocytosis involving posterior elements of the dorsal spine:
      An unusual cause of extradural spinal mass in an adult.
AB  - Langerhans cell histiocytosis (LCH) is a clonal proliferation of Langerhans cells
      occurring as an isolated lesion or as part of a systemic proliferation. It is
      commoner in children younger than 10 years of age with sparing of the posterior
      elements in more than 95% of cases. We describe a case of LCH in an adult female
      presenting with paraplegia. MRI revealed a well-defined extradural contrast
      enhancing mass at D2-D4 vertebral level involving the posterior elements of
      spine. D2-5 laminectomy with excision of lesion was performed which lead to
      marked improvement of patients neurological status. Histopathology was suggestive
      of eosinophilic granuloma. We describe the case, discuss its uniqueness and
      review the literature on this rare tumor presentation.

PMID- 23125498
TI  - The transparaspinal approach: A novel technique for one-step removal of dumb-bell
      shaped spinal tumors.
AB  - Complex dumb-bell spinal tumors are challenging surgical lesions. Combined antero
      posterior exposures have traditionally been used in their management. This
      combined exposure has the disadvantage of a two-stage operation with
      transthoracic or retroperitoneal dissection. With better understanding of
      biomechanics of spine and evolution of microsurgical technique, there has been
      resurgence of single stage surgeries, among which the transparaspinal exposure
      provides the simplest and the most direct route for resection of dumb-bell
      tumors. A 16-year-old male was admitted with history of back pain with radiation
      to left lower limb for 6 months, progressive weakness of both lower limbs for two
      months, and hesitancy of micturition for 1 month. A clinical diagnosis of cauda
      conus lesion was made. Radiological investigations revealed a complex dumb-bell
      spinal tumor extending from lower part of L2-L4 vertebra, with large paraspinal
      extension through left L3 intervertebral foramina. Tumor was successfully removed
      in one step using a transparaspinal approach. We discuss technical details of
      this novel approach along with limitations and possible complications.

PMID- 23125499
TI  - Aneurysmal bone cyst of thoracic spine mimicking spinal tuberculosis.
AB  - A 22-year-old female presented to our services with back pain and paraparesis for
      11 months. She was earlier diagnosed with tuberculosis of spine, and
      antitubercular chemotherapy was started. However her condition had worsened.
      Plain and contrast-enhanced computed tomography scans of the thorax and magnetic
      resonance imaging of the thoracic spine showed heterogenous, lytic, expansile
      lesion involving third thoracic vertebra with epidural extension and large
      bilateral paraspinal and mediastinal components. Multiple variably sized
      loculations with fluid-fluid levels were seen within the lesion. These imaging
      findings suggestive of aneurysmal bone cyst of thoracic spine were compared with
      the findings seen 11 months earlier, which were mistaken for spinal tuberculosis.
      Histopathology confirmed the diagnosis of aneurysmal bone cyst. The imaging
      features, diagnostic challenges and the lessons learned have been briefly
      discussed.

PMID- 23125500
TI  - Posterior transodontoid fixation (Kotli technique): Not for all odontoid
      fractures.

PMID- 23125501
TI  - The concern on clinical use of recombinant human bone morphogenetic protein-2.

PMID- 23125502
TI  - Use of recombinant human bone morphogenetic protein-2 (rhBMP-2) as an adjunct for
      instrumented posterior arthrodesis in the occipital cervical region: An analysis
      of safety, efficacy and dosing.

PMID- 23125503
TI  - Large ventral foramen magnum meningioma: Retrosigmoid suboccipital approach.

PMID- 23125504
TI  - Ayurveda: Finding place in own house.

PMID- 23125505
TI  - Exploratory study to evaluate tolerability, safety, and activity of Ashwagandha
      (Withania somnifera) in healthy volunteers.
AB  - Ashwagandha (Withania somnifera) (WS), a "rasayana" drug, is recommended for
      balavardhan and mamsavardhan. The study was intended to evaluate dose-related
      tolerability, safety, and activity of WS formulation in normal individuals. The
      design was prospective, open-labeled, variable doses in volunteers. Eighteen
      apparently healthy volunteers (12M:6F, age:18-30 years, and BMI: 19-30) were
      enrolled. After baseline investigations, they received WS capsules (Rx) (aqueous
      extract, 8:1) daily in two divided doses with increase in daily dosage every 10
      days for 30 days (750 mg/day *10 days, 1 000 mg/day * 10 days, 1 250 mg/day * 10
      days). Volunteers were assessed for symptoms/signs, vital functions,
      hematological and biochemical organ function tests. Muscle activity was measured
      by hand grip strength, quadriceps strength, and back extensor force. Exercise
      tolerance was determined using cycle ergometry. Lean body weight and fat% were
      computed from skin fold thickness measurement. Adverse events were recorded, as
      volunteered by the subjects. Repeated measures ANOVA, McNemar's test, and paired
      t test were employed. All but one volunteer tolerated WS without any adverse
      event. One volunteer showed increased appetite, libido, and hallucinogenic
      effects with vertigo at the lowest dose and was withdrawn from study. In six
      subjects, improvement in quality of sleep was found. Organ function tests were in
      normal range before and after the intervention. Reduction in total- and LDL-
      cholesterol and increase of strength in muscle activity was significant. Total
      body fat percentage showed a reduction trend. WS, in escalated dose, was
      tolerated well. The formulation appeared safe and strengthened muscle activity.
      In view of its traditional Rasayana use, further studies are planned to evaluate
      potential of this drug in patients of sarcopenia.

PMID- 23125506
TI  - Management of internal hemorrhoids by Kshara karma: An educational case report.
AB  - A 66-year-old male patient came to the anorectal clinic, Outpatient department,
      AVT Institute for Advanced Research, Coimbatore, Tamil Nadu, with complaints of
      prolapsing pile mass during defecation and bleeding while passing stool. The case
      was diagnosed as "Raktarsha" - 11 & 7 'o' clock position II degree internal
      hemorrhoids, deeply situated, projecting one and caused by pitta and rakta; with
      bleeding tendency. Kshara karma (application of caustic alkaline paste)
      intervention was done in this case to internal hemorrhoids under local
      anesthesia. The pile mass and per rectal bleeding resolved in 8 days and the
      patient was relieved from all symptoms within 21 days. No complications were
      reported after the procedure. The patient was followed up regularly from 2004
      onward till date and proctoscopic examination did not reveal any evidence of
      recurrence of the hemorrhoids.

PMID- 23125507
TI  - The ontological status of western science and medicine.
AB  - This paper traces the revolutionary changes that have transformed the ontological
      status of western physics and biology over the last thirty years, so as to show
      in detail how they have moved towards the perspective of the Vedic sciences. From
      this it appears that Ayurveda's more holistic approach is no longer in opposition
      to the views of physics and biology. In physics, experimental verification of
      phenomena associated with quantum correlations have forced scientists to accept
      that the macroscopic world is not strongly objective: traditional western
      scientific ontology stands rejected. One consequence is that the world is not
      necessarily reductionist i.e. based solely on the properties of its tiniest
      constituents. In biology, the 1930's discovery of homeostasis has reached a
      natural climax: the feedback instabilities, identified by Norbert Wiener as
      inevitably accompanying control processes, are now recognized to be states of
      optimal regulation, where organisms centre their function. The non-reductive
      properties of these states clearly distinguish the theory of control from
      previous physical theories; they now occupy the centre-stage of life. Possibly
      against expectation, their non-reductive nature makes their physics holistic:
      western biology seems to have broken free of reductionist physics. When Ayurveda
      and bioscience are compared in light of these little appreciated advances in
      fundamental science, the supposed differences between them are vastly reduced -
      they practically dissolve. Instead of being poles apart, the ontologies of
      western science and Ayurveda seem to have become almost identical.

PMID- 23125508
TI  - Traditional healing practice and folk medicines used by Mishing community of
      North East India.
AB  - Assam and Arunachal Pradesh have very rich tradition of herbal medicines used in
      the treatment of various ailments. Tribal communities practice different types of
      traditional healing practices. Enough documentation is available on the healing
      practices in other tribal communities except Mishing community of Assam and foot
      hill of East Siang district of Arunachal Pradesh hence the attempt was made for
      the same. A survey on folk medicinal plants and folk healers of Mishing tribe was
      conducted in few places of Lakhimpur and Dhemaji district of Assam and East Siang
      district of Arunachal Pradesh, where this ethnic group is living since time
      immemorial. All information was collected based on interview and field studies
      with local healers within the community. The identification of medicinal plants
      collected with help of indigenous healers was done. Such medicines have been
      shown to have significant healing power, either in their natural state or as the
      source of new products processed by them. This study is mainly concentrated with
      plants used to cure diseases and to enquire about different healing systems.
      Detail note on the method of preparation of precise dose, the part/parts of
      plants used and method of application is given.

PMID- 23125509
TI  - Strengthening of antioxidant defense by Azadirachta indica in alloxan-diabetic
      rat tissues.
AB  - BACKGROUND: Azadirachta indica has been reported to correct altered glycaemia in
      diabetes. OBJECTIVE: The aqueous extract of A. indica leaf and bark has been
      evaluated for its effect on antioxidant status of alloxan diabetic rats and
      compared with insulin treatment. MATERIALS AND METHODS: The oral effective dose
      of A. indica leaf (500 mg/kg body weight) and A. indica bark (100 mg/kg body
      weight) were given once daily for 21 days to separate groups of diabetic rats. At
      the end of the experimental period blood glucose level and activity of superoxide
      dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione
      reductase (GR), glucose-6-phosphate dehydrogenase (G-6-PD), and membrane lipid
      peroxidation were determined in different fractions of liver and kidney tissues.
      RESULTS: Diabetic rats showed high blood glucose (P<0.01), increased level of
      malondialdehyde (P<0.05) and a significant decrease in the activity of
      antioxidant enzymes. Treatment with insulin, A. indica leaf extract (AILE), and
      A. indica bark extract (AIBE) restored the above altered parameters close to the
      control ones. CONCLUSIONS: Both AILE and AIBE were found significantly effective
      in reducing hyperglycemia-induced oxidative stress. The findings suggest further
      investigations for the possible use of A. indica as alternative medicine to
      prevent long-term complications of diabetes.

PMID- 23125510
TI  - DNA barcoding of authentic and substitute samples of herb of the family
      Asparagaceae and Asclepiadaceae based on the ITS2 region.
AB  - BACKGROUND: Herbal drugs used to treat illness according to Ayurveda are often
      misidentified or adulterated with similar plant materials. OBJECTIVE: To aid
      taxonomical identification, we used DNA barcoding to evaluate authentic and
      substitute samples of herb and phylogenetic relationship of four medicinal plants
      of family Asparagaceace and Asclepiadaceae. MATERIALS AND METHODS: DNA extracted
      from dry root samples of two authentic and two substitutes of four specimens
      belonging to four species were subjected to polymerase chain reaction (PCR) and
      DNA sequencing. Primers for nuclear DNA (nu ITS2) and plastid DNA (matK and
      rpoC1) were used for PCR and sequence analysis was performed by Clustal W. The
      intraspecific variation and interspecific divergence were calculated using MEGA V
      4.0. STATISTICAL ANALYSIS: Kimura's two parameter model, neighbor joining and
      bootstrapping methods were used in this work. RESULTS: The result indicates the
      efficiency of amplification for ITS2 candidate DNA barcodes was 100% for four
      species tested. The average interspecific divergence is 0.12 and intraspecific
      variation was 0.232 in the case of two Asparagaceae species. In two
      Asclepiadaceae species, average interspecific divergence and intraspecific
      variation were 0.178 and 0.004 respectively. CONCLUSIONS: Our findings show that
      the ITS2 region can effectively discriminate Asparagus racemosus and Hemidesmus
      indicus from its substitute samples and hence can resolve species admixtures in
      raw samples. The ITS2 region may be used as one of the standard DNA barcodes to
      identify closely related species of family Asclepiadaceae but was noninformative
      for Asparagaceae species suggesting a need for the development of new markers for
      each family. More detailed studies involving more species and substitutes are
      warranted.

PMID- 23125511
TI  - Adjunct therapy of Ayurvedic medicine with anti tubercular drugs on the
      therapeutic management of pulmonary tuberculosis.
AB  - BACKGROUND: Pulmonary tuberculosis (PTB) is an age old disease described in Vedic
      Medicine as 'Yakshma'. Later on, in Ayurveda it earned a prefix and found way
      into mythology as 'Rajayakshma'. After the discovery of streptomycin, the
      therapeutic management of PTB received a major breakthrough. The treatment module
      changed remarkably with the formulation of newer anti-tubercular drugs (ATD) with
      appreciable success. Recent resurgence of PTB in developed countries like United
      States posed a threat to the medical community due to resistant strains.
      Consequently, WHO looked toward traditional medicine. Literature reveals that
      Ayurvedic treatment of PTB was in vogue in India before the introduction of ATD
      with limited success. Records show that 2766 patients of PTB were treated with
      Ayurvedic drugs in a tertiary care hospital in Kolkata in the year 1933-1947.
      OBJECTIVES: To evaluate the toxicity reduction and early restoration by adjunct
      therapy of Ayurvedic drugs by increasing the bio-availability of ATDs. MATERIALS
      AND METHODS: In the present study, treatment response of 99 patients treated with
      ATD as an adjunct with Aswagandha (Withania somnifera) and a multi-herbal
      formulation described in Chikitsa-sthana of Charaka samhita i.e. Chyawanprash
      were investigated. Hematological profile, sputum bacterial load count,
      immunoglobulin IgA and IgM, blood sugar, liver function test, serum creatinine
      were the assessed parameters besides blood isoniazid and pyrazinamide, repeated
      after 28 days of treatment. RESULTS: The symptoms abated, body weight showed
      improvement, ESR values were normal, there was appreciable change in IgA and IgM
      patterns and significantly increased bioavailability of isoniazid and
      pyrazinamide were recorded. CONCLUSION: This innovative clinical study coupled
      with empowered research may turn out to be promising in finding a solution for
      the treatment of PTB.

PMID- 23125512
TI  - Association of constitutional type of Ayurveda with cardiovascular risk factors,
      inflammatory markers and insulin resistance.
AB  - CONTEXT: Ayurveda propounds that diseases manifest from imbalance of doshas.
      There, have been attempts to indicate biochemical basis of constitutional types
      described in Ayurveda. AIMS: The study was intended to assess the association of
      constitutional types (Prakriti) with cardiovascular risk factors, inflammatory
      markers and insulin resistance in subjects with coronary artery disease (CAD).
      SETTINGS AND DESIGN: Hospital based cross sectional study. MATERIALS AND METHODS:
      Three hundred patients with CAD >25 years were studied. Assessment of Prakriti
      was done by using Ayusoft software. Biochemical parameters, inflammatory markers
      (hsCRP, TNF-alpha and IL-6) and insulin resistance (HOMA-IR) were measured.
      STATISTICAL ANALYSIS: Was done using EPI INFO, version 3.5.3. RESULTS: Mean age
      of patients was 60.97+/-12.5 years. Triglyceride, VLDL and LDL was significantly
      higher (P<0.0001, P<0.0001 and 0.0355, respectively) and HDL cholesterol
      (P<0.0001) significantly lower in vatta kapha (VK) Prakriti when compared with
      other constitution type. VK Prakriti was correlated with diabetes mellitus
      (r=0.169, P=0.003), hypertension (r=0.211, P<=0.0001) and dyslipidemia (r=0.541,
      P<=0.0001). Inflammatory markers; IL6, TNF alpha, hsCRP and HOMA IR was highest
      in VK Prakriti. Inflammatory markers were correlated positively with both VK and
      Kapha group. CONCLUSIONS: There is strong relation of risk factors (diabetes,
      hypertension, dyslipidemia), insulin resistance, and inflammatory markers with
      Vata Kapha and Kapha Prakriti.

PMID- 23125513
TI  - Bhishagratna achanta lakshmipathi: pioneer of ayurveda in public health.

PMID- 23125514
TI  - Future events.

PMID- 23125515
TI  - Short reports.

PMID- 23125516
TI  - Proceedings.

PMID- 23125517
TI  - Counterion and pH-Mediated Structural Changes in Charged Biopolymer Gels.
AB  - DNA solutions and gels exhibit a wide range of phenomena, many of which have not
      yet been fully understood. In the presence of multivalent counterions, attraction
      between charged DNA strands occurs. Increasing the concentration of multivalent
      ions leads to a decrease of the osmotic pressure, and a sufficiently high ion
      concentration results in the precipitation of the polymer. Replacing the
      monovalent counterions by hydrogen ions (decreasing the pH) also produces a
      marked decrease of the osmotic pressure, and at low pH a phase transition takes
      place. In this paper we analyze osmotic swelling pressure measurements and small
      angle neutron scattering (SANS) measurements made on chemically cross-linked DNA
      gels swollen in near physiological salt solutions. The effect of calcium ions is
      compared with that of decreasing the pH of the equilibrium salt solution. We
      demonstrate that both the concentration dependence of the osmotic pressure and
      the SANS response of DNA gels display significant differences in the two cases.

PMID- 23125518
TI  - Stress in Adolescents with a Chronically Ill Parent: Inspiration from Rolland's
      Family Systems-Illness Model.
AB  - This article was inspired by Rolland's Family Systems-Illness (FSI) model, aiming
      to predict adolescent stress as a function of parental illness type. Ninety-nine
      parents with a chronic medical condition, 82 partners, and 158 adolescent
      children (51 % girls; mean age = 15.1 years) participated in this Dutch study.
      The Dutch Stress Questionnaire for Children was used to measure child report of
      stress. Ill parents completed the Beck Depression Inventory. Children filled in a
      scale of the Inventory of Parent and Peer Attachment measuring the quality of
      parent attachment. Both parents filled in the Parent-Child-Interaction
      Questionnaire-Revised. We conducted multilevel regression analyses including
      illness type, the ill parent's depressive symptoms, family functioning (quality
      of marital relationship, parent-child interaction, and parent attachment), and
      adolescents' gender and age. Four regression analyses were performed separately
      for each illness type as defined by disability (Model 1), and onset (Model 2),
      course (Model 3), and outcome of illness (Model 4). In all models, higher
      adolescent stress scores were linked to lower quality of parent-child interaction
      and parent attachment, and adolescents' female gender. The four models explained
      approximately 37 % of the variance in adolescent stress between individuals and
      43-44 % of the variance in adolescent stress between families. Adolescent stress
      was not related to parental illness type. Our results partially supported the FSI
      model stating that family functioning is essential in point of child adjustment
      to parental illness. In the chronic stage of parental illness, adolescent stress
      does not seem to vary depending on illness type.

PMID- 23125519
TI  - The cost of Medicaid savings: the potential detrimental public health impact of
      neonatal circumcision defunding.
AB  - OBJECTIVE: To project the increased incidence of HIV and subsequent costs
      resulting from the expected decreased rate of circumcision due to Medicaid
      defunding in one southeastern state. METHODS: Using 2009 South Carolina (SC)
      Medicaid birth cohort (n = 29, 316), we calculated expected heterosexually
      acquired HIV cases at current circumcision rates. To calculate age/race/gender
      specific HIV incidence rates, we used 2009 South Carolina Department of Health
      and Environmental Control reported gender and race specific HIV cases, CDC
      reported age distribution of HIV cases, and 2009 S.C. population data. Accounting
      for current circumcision rates, we calculated the change in incidence of
      heterosexually acquired HIV assuming circumcision provides 60% protection against
      HIV transmission to males and 46% protection against male to female transmission.
      Published lifetime cost of HIV was used to calculate the cost of additional HIV
      cases. RESULTS: Assuming Medicaid circumcision rates decrease from current
      nationally reported levels to zero secondary to defunding, we project an
      additional 55 male cases of HIV and 47 female cases of HIV among this birth
      cohort. The total cost discounted to time of infection of these additional HIV
      cases is $20,924,400 for male cases and $17,711,400 for female cases. The cost to
      circumcise males in this birth cohort at currently reported rates is $4,856,000.
      CONCLUSIONS: For every year of decreased circumcision rates due to Medicaid
      defunding, we project over 100 additional HIV cases and $30,000,000 in net
      medical costs.

PMID- 23125520
TI  - Flexible Distributed Lag Models using Random Functions with Application to
      Estimating Mortality Displacement from Heat-Related Deaths.
AB  - As climate continues to change, scientists are left to analyze the effects these
      changes will have on the public. In this article, a flexible class of distributed
      lag models are used to analyze the effects of heat on mortality in four major
      metropolitan areas in the U.S. (Chicago, Dallas, Los Angeles, and New York).
      Specifically, the proposed methodology uses Gaussian processes as a prior model
      for the distributed lag function. Gaussian processes are adequately flexible to
      capture a wide variety of distributed lag functions while ensuring smoothness
      properties of process realizations. Additionally, the proposed framework allows
      for probabilistic inference of the maximum lag. Applying the proposed methodology
      revealed that mortality displacement (or, harvesting) was present for most age
      groups and cities analyzed suggesting that heat advanced death in some
      individuals. Additionally, the estimated shape of the DL functions gave evidence
      that prolonged heat exposure and highly variable temperatures pose a threat to
      public health.

PMID- 23125521
TI  - Retell as an Indicator of Reading Comprehension.
AB  - The purpose of this narrative synthesis is to determine the reliability and
      validity of retell protocols for assessing reading comprehension of students in
      grades K-12. Fifty-four studies were systematically coded for data related to the
      administration protocol, scoring procedures, and technical adequacy of the retell
      component. Retell was moderately correlated with standardized measures of reading
      comprehension and, with older students, had a lower correlation with decoding and
      fluency. Literal information was retold more frequently than inferential, and
      students with learning disabilities or reading difficulties needed more supports
      to demonstrate adequate recall. Great variability was shown in the prompting
      procedures, but scoring methods were more consistent across studies. The
      influences of genre, background knowledge, and organizational features were often
      specific to particular content, texts, or students. Overall, retell has not yet
      demonstrated adequacy as a progress monitoring instrument.

PMID- 23125522
TI  - Potential role of kringle-integrin interaction in plasmin and uPA actions (a
      hypothesis).
AB  - We previously showed that the kringle domains of plasmin and angiostatin, the N
      terminal four kringles (K1-4) of plasminogen, directly bind to integrins.
      Angiostatin blocks tumor-mediated angiogenesis and has great therapeutic
      potential. Angiostatin binding to integrins may be related to the
      antiinflammatory action of angiostatin. We reported that plasmin induces signals
      through protease-activated receptor (PAR-1), and plasmin-integrin interaction may
      be required for enhancing plasmin concentration on the cell surface, and enhances
      its signaling function. Angiostatin binding to integrin does not seem to induce
      proliferative signals. One possible mechanism of angiostatin's inhibitory action
      is that angiostatin suppresses plasmin-induced PAR-1 activation by competing with
      plasmin for binding to integrins. Interestingly, plasminogen did not interact
      with alphavbeta3, suggesting that the alphavbeta3-binding sites in the kringle
      domains of plasminogen are cryptic. The kringle domain of urokinase-type
      plasminogen activator (uPA) also binds to integrins. The uPA-integrin interaction
      enhances uPA concentrations on the cell surface and enhances plasminogen
      activation on the cell surface. It is likely that integrins bind to the kringle
      domain, and uPAR binds to the growth factor-like domain (GFD) of uPA
      simultaneously, making the uPAR-uPA-integrin ternary complex. We present a
      docking model of the ternary complex.

PMID- 23125524
TI  - The plasminogen receptor, Plg-R(KT), and macrophage function.
AB  - When plasminogen binds to cells its activation to plasmin is markedly enhanced
      compared to the reaction in solution. Thus, cells become armed with the broad
      spectrum proteolytic activity of plasmin. Cell-surface plasmin plays a key role
      in macrophage recruitment during the inflammatory response. Proteins exposing
      basic residues on the cell surface promote plasminogen activation on eukaryotic
      cells. We have used a proteomics approach combining targeted proteolysis with
      carboxypeptidase B and multidimensional protein identification technology,
      MudPIT, and a monocyte progenitor cell line to identify a novel transmembrane
      protein, the plasminogen receptor, Plg-R(KT). Plg-R(KT) exposes a C-terminal
      lysine on the cell surface in an orientation to bind plasminogen and promote
      plasminogen activation. Here we review the characteristics of this new protein,
      with regard to membrane topology, conservation of sequence across species, the
      role of its C-terminus in plasminogen binding, its function in plasminogen
      activation, cell migration, and its role in macrophage recruitment in the
      inflammatory response.

PMID- 23125523
TI  - Ectonucleotidases in solid organ and allogeneic hematopoietic cell
      transplantation.
AB  - Extracellular nucleotides are ubiquitous signalling molecules which modulate
      distinct physiological and pathological processes. Nucleotide concentrations in
      the extracellular space are strictly regulated by cell surface enzymes, called
      ectonucleotidases, which hydrolyze nucleotides to the respective nucleosides.
      Recent studies suggest that ectonucleotidases play a significant role in
      inflammation by adjusting the balance between ATP, a widely distributed
      proinflammatory danger signal, and the anti-inflammatory mediator adenosine.
      There is increasing evidence for a central role of adenosine in alloantigen
      mediated diseases such as solid organ graft rejection and acute graft-versus-host
      disease (GvHD). Solid organ and hematopoietic cell transplantation are
      established treatment modalities for a broad spectrum of benign and malignant
      diseases. Immunological complications based on the recognition of nonself
      antigens between donor and recipient like transplant rejection and GvHD are still
      major challenges which limit the long-term success of transplantation. Studies in
      the past two decades indicate that purinergic signalling influences the severity
      of alloimmune responses. This paper focuses on the impact of ectonucleotidases,
      in particular, NTPDase1/CD39 and ecto-5'-nucleotidase/CD73, on allograft
      rejection, acute GvHD, and graft-versus-leukemia effect, and on possible clinical
      implications for the modulation of purinergic signalling after transplantation.

PMID- 23125525
TI  - CD73-generated adenosine: orchestrating the tumor-stroma interplay to promote
      cancer growth.
AB  - Despite the coming of age of cancer immunotherapy, clinical benefits are still
      modest. An important barrier to successful cancer immunotherapy is that tumors
      employ a number of mechanisms to facilitate immune escape, including the
      production of anti-inflammatory cytokines, the recruitment of regulatory immune
      subsets, and the production of immunosuppressive metabolites. Significant
      therapeutic opportunity exists in targeting these immunosuppressive pathways. One
      such immunosuppressive pathway is the production of extracellular adenosine by
      CD73, an ectonucleotidase overexpressed in various types of cancer. We hereafter
      review the biology of CD73 and its role in cancer progression and metastasis. We
      describe the role of extracellular adenosine in promoting tumor growth through
      paracrine and autocrine action on tumor cells, endothelial cells, and immune
      cells.

PMID- 23125526
TI  - In silico biology of H1N1: molecular modelling of novel receptors and docking
      studies of inhibitors to reveal new insight in flu treatment.
AB  - Influenza is an infectious disease caused by RNA viruses of the family
      Orthomyxoviridae. The new influenza H1N1 viral stain has emerged by the genetic
      combination of genes from human, pig, and bird's H1N1 virus. The influenza virus
      is roughly spherical and is enveloped by a lipid membrane. There are two
      glycoproteins in this lipid membrane; namely, hemagglutinin (HA) which helps in
      attachment of the viral strain on the host cell surface and neuraminidase (NA)
      that is responsible for initiation of viral infection. We have developed homology
      models of both Hemagglutinin and Neuraminidase receptors from H1N1 strains in
      eastern India. The docking studies of B-Sialic acid and O-Sialic acid in the
      optimized and energy-minimized homology models show important H-bonding
      interactions with ALA142, ASP230, GLN231, GLU232, and THR141. This information
      can be used for structure-based and pharmacophore-based new drug design. We have
      also calculated ADME properties (Human Oral Absorption (HOA) and % HOA) for
      Oseltamivir which have been subject of debate for long.

PMID- 23125527
TI  - Ectonucleotidases in cancer and inflammation.

PMID- 23125529
TI  - Maternal infectious diseases, antimicrobial therapy or immunizations: Very few
      contraindications to breastfeeding.

PMID- 23125528
TI  - Long-term MRI tracking of dual-labeled adipose-derived stem cells homing into
      mouse carotid artery injury.
AB  - BACKGROUND: Stem cell therapy has shown great promise for regenerative repair of
      injured or diseased tissues. Adipose-derived stem cells (ADSCs) have become
      increasingly attractive candidates for cellular therapy. Magnetic resonance
      imaging has been proven to be effective in tracking magnetic-labeled cells and
      evaluating their clinical relevance after cell transplantation. This study
      investigated the feasibility of imaging green fluorescent protein-expressing
      ADSCs (GFP-ADSCs) labeled with superparamagnetic iron oxide particles, and
      tracked them in vivo with noninvasive magnetic resonance imaging after cell
      transplantation in a model of mouse carotid artery injury. METHODS: GFP-ADSCs
      were isolated from the adipose tissues of GFP mice and labeled with
      superparamagnetic iron oxide particles. Intracellular stability, proliferation,
      and viability of the labeled cells were evaluated in vitro. Next, the cells were
      transplanted into a mouse carotid artery injury model. Clinical 3 T magnetic
      resonance imaging was performed immediately before and 1, 3, 7, 14, 21, and 30
      days after cell transplantation. Prussian blue staining and histological analysis
      were performed 7 and 30 days after transplantation. RESULTS: GFP-ADSCs were found
      to be efficiently labeled with superparamagnetic iron oxide particles, with no
      effect on viability and proliferation. Homing of the labeled cells into the
      injured carotid artery tissue could be monitored by magnetic resonance imaging.
      CONCLUSION: Magnetically labeled ADSCs with expression of GFP can home into sites
      of vascular injury, and may provide new insights into understanding of cell-based
      therapy for cardiovascular lesions.

PMID- 23125531
TI  - A New Route to Azadithiolato Complexes.
AB  - The reaction of [(MeC(5)H(4))(2)Ti(SH)(2)] with cyclic imines with the formula
      (CH(2)NR)(3) gives 2-aza-1,3-dithiolato chelate complexes
      [(MeC(5)H(4))(2)Ti{(SCH(2))(2)NR}] (1, R = Ph; 2, R = Me; 3, R = CH(2)Ph). These
      compounds demonstrate that azadithiolate ligands can exist on mononuclear metal
      centers. The complexes were characterized by (1)H NMR spectroscopy, ESI-mass
      spectrometry, and X-ray crystallography. Variable-temperature (1)H NMR studies
      reveal that the dithiolate ligands undergo ring inversion like other
      dithiatitanacyclohexanes. Treatment of [(MeC(5)H(4))(2)Ti{(SCH(2))(2)NPh}] (1)
      with [Fe(benzylideneacetone)(CO)(3)] afforded [Fe(2){(SCH(2))(2)NPh}(CO)(6)] in
      good yield.

PMID- 23125533
TI  - Challenges for medical residency in hematology and transfusion medicine in
      Brazil.

PMID- 23125530
TI  - beta-Catenin Does Not Confer Tumorigenicity When Introduced into Partially
      Transformed Human Mesenchymal Stem Cells.
AB  - Although osteosarcoma is the most common primary malignant bone tumor in children
      and adolescents, its cell of origin and the genetic alterations are unclear.
      Previous studies have shown that serially introducing hTERT, SV40 large TAg, and
      H-Ras transforms human mesenchymal stem cells into two distinct sarcomas cell
      populations, but they do not form osteoid. In this study, beta-catenin was
      introduced into mesenchymal stem cells already containing hTERT and SV40 large
      TAg to analyze if this resulted in a model which more closely recapitulated
      osteosarcoma. Results. Regardless of the level of induced beta-catenin expression
      in the stable transfectants, there were no marked differences induced in their
      phenotype or invasion and migration capacity. Perhaps more importantly, none of
      them formed tumors when injected into immunocompromised mice. Moreover, the
      resulting transformed cells could be induced to osteogenic and chondrogenic
      differentiation but not to adipogenic differentiation. Conclusions. beta-catenin,
      although fostering osteogenic differentiation, does not induce the malignant
      features and tumorigenicity conveyed by oncogenic H-RAS when introduced into
      partly transformed mesenchymal stem cells. This may have implications for the
      role of beta-catenin in osteosarcoma pathogenesis. It also may suggest that
      adipogenesis is an earlier branch point than osteogenesis and chondrogenesis in
      normal mesenchymal differentiation.

PMID- 23125534
TI  - BCR-ABL rearrangement and HLA antigens: a possible link to leukemia pathogenesis
      and immunotherapy.

PMID- 23125535
TI  - Comment on: clinical impact of systematic nutritional care in adults submitted to
      allogeneic hematopoietic stem cell transplantation.

PMID- 23125536
TI  - Importance of functional evaluation after hematopoietic cell transplantation.

PMID- 23125537
TI  - Anemia and the blood donor.

PMID- 23125538
TI  - Blood donation, blood supply, iron deficiency and anemia - it is time to shift
      attention back to donor health.

PMID- 23125539
TI  - A step towards the cure of Burkitt's lymphoma in developing countries.

PMID- 23125540
TI  - Clinical impact of systematic nutritional care in adults submitted to allogeneic
      hematopoietic stem cell transplantation.
AB  - BACKGROUND: The development of nutrition care programs for patients undergoing
      hematopoietic stem cell transplantation is necessity in view of the rapid and
      aggressive consequences frequently seen with this procedure. Patients require
      constant care to reduce complications and to contribute to the success of
      therapy. METHODS: In an attempt to ascertain the impact of systematic nutritional
      care on patients submitted to allogeneic hematopoietic stem cell transplantation,
      the present study assessed the nutritional and clinical status, use of parenteral
      nutrition, and complication and mortality rates in two groups of patients, who
      were submitted to transplantation between April 2003 and December 2004 (Non
      intervention Group - NIG; n = 57) and between March 2006 and January 2008
      (Intervention Group - IG; n = 34). RESULTS: There were no significant differences
      between groups in terms of clinical or nutritional profiles. Additionally, the
      length of hospital stay and complication and mortality rates were similar for
      both groups. However, time on parenteral nutrition during treatment was shorter
      for the IG [median 6.5 days (range: 1-28) for related donor recipients and 11
      days (range: 1-21) for unrelated donor recipients] than for the NIG [median 20.5
      days (range, 4-73) for patients submitted to myeloablative conditioning and 18.5
      days (range: 11-59 days) for those submitted to nonablative conditioning].
      CONCLUSION: The implementation of a nutritional follow-up and therapy protocol
      for adult patients submitted to hematopoietic stem cell transplantation shortens
      the duration of parenteral nutrition. It certainly has an impact on
      hospitalization costs and, potentially, on the rate of complications, even though
      this was not demonstrated in this study.

PMID- 23125541
TI  - A model of genetic guidance for hemoglobinopathy patients and laboratory
      diagnosis of family members as educational and preventive measures.
AB  - BACKGROUND: The high frequency of hemoglobinopathies in Brazil constitutes a
      public health problem and thus educational and preventive measures are necessary
      to reduce the incidence. Genetic guidance, a modality of genetic counseling, and
      family screening are measures that can assist in reproductive decisions and
      mitigate clinical, psychological and social problems of families with these
      disorders. OBJECTIVE: The objective of the current study was to evaluate the
      effectiveness of educational and preventive measures for hemoglobinopathies using
      genetic guidance and laboratory screening of families. METHODS: The diagnoses of
      patients with hemoglobinopathies were confirmed and then the level of knowledge
      about their disease was evaluated and genetic guidance was provided. Three months
      later, the level of assimilated information of these patients was evaluated. In
      addition, laboratory diagnosis of family members was carried out. RESULTS:
      Diagnosis of sickle cell anemia was confirmed for most patients. Moreover, the
      majority of the patients who had a low level of knowledge before genetic guidance
      (68.8%) demonstrated a higher level of assimilated information after the process
      (81.8%). Almost 70% of the family members had hemoglobin changes and some had
      hemoglobinopathies(2.6%). They were duly informed about the results of the
      examinations, which made it possible to investigate further. CONCLUSION: Genetic
      guidance and family screening were effective preventive and educational measures
      that improved the quality of life of patients, preventing complications and
      sequels and allowed the referral of those who may transmit altered genes for
      clinical diagnosis and to genetic counseling services.

PMID- 23125542
TI  - Functional evaluation indicates physical losses after hematopoietic stem cell
      transplantation.
AB  - OBJECTIVE: To perform a function evaluation of patients before and after
      hematopoietic stem cell transplantation. METHODS: From November 2008 to November
      2010, 29 female (58%) and 21 male patients (42%) with median age of 48 years
      (range: 24-67) were enrolled in this study. Data collection was performed before
      and after autologous or allogeneic hematopoietic stem cell transplantation.
      Evaluation instruments included the 2-minute walking test to evaluate gait
      performance with assessment of the oxygen saturation, heart rate and Borg Scale
      before and after the test; grip strength for strength evaluation, Schober Test
      for spine mobility testing and maximum and adapted activity scores of the Human
      Activity Profile questionnaire to test functionality in daily activities.
      RESULTS: Fifty patients were evaluated at baseline; six did not undergo
      hematopoietic stem cell transplantation (three died, one refused and two were
      excluded). Thus 44/50 (88% - 21 allogeneic and 23 autologous) transplantations
      were performed. Only 33 of the 44 patients (75%) performed evaluations after
      transplantation (nine died and two were excluded). Of the patients who performed
      both evaluations, significantly lower values were found in the evaluation after
      transplantation for the 2-minute walking test (p-value = 0.004), grip strength of
      both right and left hands (p-value = 0.004 and p-value < 0.0001, respectively),
      the Schober Test, and maximum and adapted activity scores (p-value < 0.0001). The
      heart rate was higher (p-value = 0.01) before the 2-minute walking test and
      oxygen saturation was higher (p-value = 0.02) after. CONCLUSION: Statistical
      differences indicate functional impairment after transplantation showing physical
      losses in this population.

PMID- 23125543
TI  - Serum concentrations of nitrite and malondialdehyde as markers of oxidative
      stress in chronic myeloid leukemia patients treated with tyrosine kinase
      inhibitors.
AB  - BACKGROUND: Chronic myeloid leukemia is a neoplasm characterized by clonal
      expansion of hematopoietic progenitor cells resulting from the (9:22)(q34,11)
      translocation. The tyrosine kinase abl fusion protein,the initial leukemogenic
      event in chronic myeloid leukemia, is constitutively activated thus inducing the
      production of reactive oxygen species. Of particular relevance is the fact that
      an increase in reactive oxygen species can facilitate genomic instability and may
      contribute to disease progression. OBJECTIVE: To evaluate oxidative stress by
      determining the levels of malondialdehyde and nitrite in chronic myeloid leukemia
      patients under treatment with 1st and 2nd generation tyrosine kinase inhibitors
      monitored at a referral hospital in Fortaleza, Ceara. METHODS: A cross-sectional
      study was performed of 64 male and female adults. Patients were stratified
      according to treatment. The levels of malondialdehyde and nitrite were determined
      by spectrophotometry. Statistical differences between groups were observed using
      the Student t-test and Fisher's exact test. The results are expressed as mean +/-
      standard error of mean. The significance level was set for a p-value < 0.05 in
      all analyses. RESULTS: The results show significantly higher mean concentrations
      of nitrite and malondialdehyde in chronic myeloid leukemia patients using second
      generation tyrosine kinase inhibitors compared to patients on imatinib.
      CONCLUSION: It follows that chronic myeloid leukemia patients present higher
      oxidative activity and that the increases in oxidative damage markers can
      indicate resistance to 1st generation tyrosine kinase inhibitors.

PMID- 23125544
TI  - Etiology of anemia of blood donor candidates deferred by hematologic screening.
AB  - OBJECTIVE: Iron deficiency is the most common cause of anemia and one of the main
      factors in the clinical deferral of blood donors. This fact prompted the current
      study that aimed to determine the prevalence and etiology of anemia in blood
      donor candidates and to evaluate the hematological screening technique used for
      the exclusion of these donors. METHODS: This was a prospective study that
      compared two groups (Anemic and Non-anemic). Initially screening for anemia was
      performed by manually measuring hemoglobin (Bioclin((r)) Kit); the results were
      subsequently compared with an automated screening method (Coulter T-890). The
      etiology was investigated by hemoglobin electrophoresis in alkaline and acid pH,
      Hb A2 dosage and measurement of the ferritin concentration by
      immunoagglutination. Differences and associations of interest were analyzed using
      the Yates and McNemar's Chi-square tests and the Fisher, Mann-Whitney, Wilcoxon
      and Kruskal-Wallis tests. RESULTS: The deferral rate due to anemia was 4.2%; iron
      deficiency was identified in 37.5% and beta thalassemia in 9.3% of the excluded
      candidates. There was a significant discrepancy between the two techniques used
      to measure hemoglobin with 38.1% of initially deferred donors presenting normal
      hemoglobin levels by the automated method. CONCLUSION: The results show a high
      rate of blood donors being deferred for anemia and confirm that iron deficiency
      is the most prevalent cause. The discrepancies found by comparing screening
      methods suggest that hemoglobin and hematocrit levels should be confirmed before
      deferring a donor due to anemia; this may increase supplies in blood banks.

PMID- 23125545
TI  - Clinical course and prognostic factors of children with Burkitt's lymphoma in a
      developing country: the experience of a single centre in Brazil.
AB  - OBJECTIVE: Burkitt's lymphoma is the most common subtype of non-Hodgkin lymphoma
      in children. The aim of this study was to characterize the clinical course and
      prognostic factors of children and adolescents with Burkitt's lymphoma treated in
      the Hematology Unit of Hospital das Clinicas, Universidade Federal de Minas
      Gerais (UFMG). METHODS: A retrospective cohort study was made of 50 consecutive
      cases of children and adolescents aged 16 years or less with Burkitt's lymphoma
      admitted between January 1981 and December 2007. Prognostic factors associated
      with death were evaluated using the Kaplan-Meier method and compared by the two
      tailed log-rank test. RESULTS: The median age at diagnosis was 4.7 years. Most
      patients had abdominal tumors (66.7%) and advanced disease (68.9%) at diagnosis.
      Thirty-eight patients (84.4%) achieved complete clinical remission and 33 (73.3%)
      were alive at the first remission. Twelve children (26.7%) died. The median
      follow-up was 35 months with the probability of overall survival being 73% (89.2%
      and 35.7% for patients with uric acid < 7 mg/dL and >= 7.0 mg/dL, respectively -
      p-value < 0.001). Uric acid was the only significant prognostic factor at
      diagnosis. CONCLUSION: Our findings confirm the favorable prognosis of children
      with Burkitt's lymphoma even when treated with intermediate doses of methotrexate
      (500 mg/m2). Survival was significantly lower for individuals with concentrations
      of uric acid > 7 mg/dL.

PMID- 23125548
TI  - Neonatal screening in the state of Piaui: an urgent need - a study on the
      prevalence of sickle cell disease in newborns.

PMID- 23125546
TI  - Chronic myeloid leukemia treatment guidelines: Brazilian Association of
      Hematology, Hemotherapy and Cell Therapy. Brazilian Medical Association
      Guidelines Project - 2012.

PMID- 23125547
TI  - Use of antifungal drugs in hematology.
AB  - Invasive fungal disease represents a major complication in hematological
      patients. Antifungal agents are frequently used in hematologic patients for
      different purposes. In neutropenic patients, antifungal agents may be used as
      prophylaxis, as empiric or preemptive therapy, or to treat an invasive fungal
      disease that has been diagnosed. The hematologist must be familiar with the
      epidemiology, diagnostic tools and strategies of antifungal use, as well as the
      pharmacologic proprieties of the different antifungal agents. In this paper the
      principal antifungal agents used in hematologic patients will be discussed as
      will the clinical scenarios where these agents have been used.

PMID- 23125549
TI  - Leukocyte superoxide dismutase activity in patients with chronic myeloid
      leukemia.

PMID- 23125550
TI  - The utility of multiparametric flow cytometry for the detection of minimal
      residual disease in acute lymphoblastic leukemia.

PMID- 23125551
TI  - Developing a Strategic Plan for Transitioning to Healthcare Knowledge Services
      Centers (HKSCs).
AB  - Facing a negative trend in the form of downsizing, layoffs, and closures, a small
      committee of hospital librarians in New England was formed in 2004 to provide
      library advocacy. Between 2008 and 2010, 23 hospital libraries closed in New
      England. In 2010, the committee shifted its focus from advocacy to a platform for
      change. This resulted in the creation of the Healthcare Knowledge Services Center
      (HKSC) Template. The Template is the basis for a 3-phased, 5-year strategic plan
      to establish several regional pilots, transitioning traditional hospital
      libraries to healthcare knowledge services centers. This article focuses on Phase
      One of the strategic plan, Development.

PMID- 23125552
TI  - Psychometric Properties of Maze Tasks in Middle School Students.
AB  - Maze tasks have appealing properties as progress-monitoring tools, but there is a
      need for a thorough examination of the psychometric properties of Maze tasks
      among middle school students. We evaluated form effects, reliability, validity,
      and practice effects of Maze among students in Grades 6 through 8. We
      administered the same (familiar) and novel Maze passages for progress monitoring
      of a reading intervention among typical readers (n = 588), struggling readers
      receiving researcher-provided intervention (n = 471), and struggling readers not
      receiving intervention (n = 284). Form effects accounted for significant variance
      in Maze performance. Familiar passages had greater test-retest reliability than
      novel passages. Both administrative conditions had similar, moderate correlations
      (validity coefficients) with other measures of reading fluency and comprehension.
      There were also significant practice effects. Students who read the same passage
      showed steeper slopes in Maze performance than students who read different
      passages over time. Practice effects were influenced by beginning levels of
      reading comprehension and by intervention status.

PMID- 23125553
TI  - Fetal and neonatal levels of omega-3: effects on neurodevelopment, nutrition, and
      growth.
AB  - Nutrition in pregnancy, during lactation, childhood, and later stages has a
      fundamental influence on overall development. There is a growing research
      interest on the role of key dietary nutrients in fetal health. Omega-3
      polyunsaturated fatty acids (n-3 LCPUFAs) play an important role in brain
      development and function. Evidence from animal models of dietary n-3 LCPUFAs
      deficiency suggests that these fatty acids promote early brain development and
      regulate behavioral and neurochemical aspects related to mood disorders (stress
      responses, depression, and aggression and growth, memory, and cognitive
      functions). Preclinical and clinical studies suggest the role of n-3 LCPUFAs on
      neurodevelopment and growth. n-3 LCPUFAs may be an effective adjunctive factor
      for neural development, growth, and cognitive development, but further large
      scale, well-controlled trials and preclinical studies are needed to examine its
      clinical mechanisms and possible benefits. The present paper discusses the use of
      n-3 LCPUFAs during different developmental stages and the investigation of
      different sources of consumption. The paper summarizes the role of n-3 LCPUFAs
      levels during critical periods and their effects on the children's
      neurodevelopment, nutrition, and growth.

PMID- 23125554
TI  - Effect of composting on dissolved organic matter in animal manure and its binding
      with Cu.
AB  - The agricultural application of raw animal manure introduces large amounts of
      dissolved organic matter (DOM) into soil and would increase transport of heavy
      metals such as Cu which are widely present in animal manure. The purpose of this
      research was to evaluate the evolution of DOM from pig and cattle manures during
      composting through excitation-emission matrix (EEM) fluorescence spectroscopy and
      the binding ability of DOM toward copper (Cu) ions with the aid of fluorescence
      quenching titration. The excitation-emission matrix spectra indicated that
      tyrosine-like, tryptophan-like, and soluble microbial byproduct-like fluorescence
      decreased significantly, while humic-like and fulvic-like fluorescence increased
      and became the main peaks in composted manure DOM. Fluorescence quenching
      titration showed that the complexing capacities of pig and cattle manure DOM
      decreased after composting. Correlation analysis confirmed that complexing
      capacity of DOM positively and significantly correlates with tyrosine-like and
      soluble microbial byproduct-like materials which mostly degraded after
      composting. These results would suggest that the ability of manure DOM to complex
      with Cu is inhibited as a result of reduced protein-like materials after
      composting.

PMID- 23125555
TI  - Grade 2 spondylolisthesis at L4-5 treated by XLIF: safety and midterm results in
      the "worst case scenario".
AB  - Spondylolisthesis is one of the most common indications for spinal surgery.
      However, no one approach has been proven to be more effective in treating
      spondylolisthesis. Recent advances in minimally invasive spine technology have
      allowed for different approaches to be applied to this indication, notably
      extreme lateral interbody fusion (XLIF). The risk, however, of using XLIF in
      treating grade II spondylolisthesis is the ventral position of the lumbar plexus,
      particularly at L4-5. OBJECTIVE: This study reports the safety and midterm
      clinical and radiographic outcomes of patients with grade II lumbar
      spondylolisthesis treated with XLIF. METHODS: 63 patients with grade II
      spondylolisthesis and spinal stenosis were treated with XLIF and were available
      for 12-month followup. Of those, 61 (97%) were treated at L4-5. Clinical (VAS,
      complications, and reoperation rate) and radiographic (anterolisthesis, disk
      height, and fusion) parameters were assessed. STUDY DESIGN: Data were collected
      via a prospective registry and analyzed retrospectively. RESULTS: Sixty-three
      patients were available for evaluations at least one year postoperatively.
      Average pain (visual analog scale) decreased from a score of 8.7 at baseline to
      2.2 at 12 months postoperatively. Average anterior slippage was reduced by 73%
      and was well maintained. Average disk height (4.6 mm pre-op and 9.0 mm post-op)
      nearly doubled after surgery. Slight settling (average 1.3 mm) occurred over the
      twelve-month follow-up period. There were no neural injuries and no nonunions
      noted. CONCLUSIONS: XLIF is a safe and effective minimally invasive treatment
      alternative for grade II spondylolisthesis. Real-time neurological monitoring and
      attention to technique are mandatory.

PMID- 23125556
TI  - Fasting blood glucose and lipid profile alterations following twelve-month
      androgen deprivation therapy in men with prostate cancer.
AB  - PURPOSE: In this retrospective study, we aimed to investigate the effects of
      androgen deprivation therapy (ADT) on blood glucose and blood cholesterol levels
      over a 12-month period. MATERIALS AND METHODS: Between January 2010 and June
      2012, the data of 44 patients with prostate cancer who were receiving ADT were
      collected from a hospital database. Patients with additional malignancy or
      diabetes and those who had been prescribed and were currently taking cholesterol
      lowering medication were excluded from the study. Data (including fasting blood
      glucose levels and a cholesterol profile) were collected and analysed
      statistically. A P value <0.05 was considered statistically significant. RESULTS:
      Twelve months after the initiation of ADT, fasting blood glucose (FBG), total
      cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density
      lipoprotein (HDL) cholesterol, and triglyceride (TG) levels changed. FBG, TC, LDL
      cholesterol, and TG increased significantly (P = 0.009, 0.000, 0.000, and 0.000,
      resp.), while HDL cholesterol decreased (P = 0.000). CONCLUSION: ADT may increase
      FBG, TC, LDL cholesterol, and TG but decrease HDL cholesterol by the end of a
      year of treatment. Therefore, close followup may be needed as a consequence of
      one-year ADT regarding metabolic alterations.

PMID- 23125557
TI  - Summer watering patterns of mule deer in the Great Basin Desert, USA:
      implications of differential use by individuals and the sexes for management of
      water resources.
AB  - Changes in the abundance and distribution of free water can negatively influence
      wildlife in arid regions. Free water is considered a limiting factor for mule
      deer (Odocoileus hemionus) in the Great Basin Desert. Consequently, a better
      understanding of differential use of water by individuals and the sexes could
      influence the conservation and management of mule deer and water resources in
      their habitats. We deployed remote cameras at all known water sources (13
      wildlife water developments and 4 springs) on one mountain range in western Utah,
      USA, during summer from 2007 to 2011 to document frequency and timing of water
      use, number of water sources used by males and females, and to estimate
      population size from individually identified mule deer. Male and female mule deer
      used different water sources but visited that resource at similar frequencies.
      Individual mule deer used few water sources and exhibited high fidelity to that
      resource. Wildlife water developments were frequently used by both sexes. Our
      results highlight the differing use of water sources by sexes and individual mule
      deer. This information will help guide managers when siting and reprovisioning
      wildlife water developments meant to benefit mule deer and will contribute to the
      conservation and management of this species.

PMID- 23125558
TI  - Ethylene inhibitors enhance shoot organogenesis of gloxinia (Sinningia speciosa).
AB  - Shoot organogenesis and plant regeneration in Sinningia speciosa were improved
      using ethylene inhibitors. The leaf explants were cultured on initial shoot
      regeneration media (MS media with BAP at 2 mg/L + NAA at 0.1 mg/L) supplemented
      with different concentrations of aminoethoxyvinylglycine (AVG), cobalt chloride
      (CoCl2), and silver thiosulphate (STS). The addition of AVG, CoCl2, and STS
      significantly improved the regeneration frequency giving higher shoots per
      explant and longer shoot length. The highest shoot growth was found when STS at 5
      mg/L was incorporated with generation medium, performing highest regeneration
      frequency with highest number of shoots. This treatment (STS at 5 mg/L) produced
      40% more shoots per explant compared to control followed by STS at 10 mg/L with
      increasing 37% more shoots compared to control. In the cases of AVG and CoCl2 the
      highest shoot number per explant was found at 1 mg/L. Treated with AVG and CoCl2
      at 1 mg/L increased shoot number by 16 and 12%, respectively, compared to
      control. Ethylene inhibitors could be used as a possible micropropagation and
      plant transformation protocol in S. speciosa for plant regenerations.

PMID- 23125559
TI  - Once is Enough: N400 Indexes Semantic Integration of Novel Word Meanings from a
      Single Exposure in Context.
AB  - We investigated the impact of contextual constraint on the integration of novel
      word meanings into semantic memory. Adults read strongly or weakly constraining
      sentences ending in known or unknown (novel) words as scalp-recorded electrical
      brain activity was recorded. Word knowledge was assessed via a lexical decision
      task in which recently seen known and unknown word sentence endings served as
      primes for semantically related, unrelated, and synonym/identical target words.
      As expected, N400 amplitudes to target words preceded by known word primes were
      reduced by prime-target relatedness. Critically, N400 amplitudes to targets
      preceded by novel primes also varied with prime-target relatedness, but only when
      they had initially appeared in highly constraining sentences. This demonstrates
      for the first time that fast-mapped word representations can develop strong
      associations with semantically related word meanings and reveals a rapid neural
      process that can integrate information about word meanings into the mental
      lexicon of young adults.

PMID- 23125560
TI  - Synthesis, Spectroscopic Characterization, and In Vitro Antimicrobial Studies of
      Pyridine-2-Carboxylic Acid N'-(4-Chloro-Benzoyl)-Hydrazide and Its Co(II),
      Ni(II), and Cu(II) Complexes.
AB  - N-substituted pyridine hydrazide (pyridine-2-carbonyl chloride and 4-chloro
      benzoic acid hydrazide) undergoes hydrazide formation of the iminic carbon
      nitrogen double bond through its reaction with cobalt(II), nickel(II), and
      copper(II) metal salts in ethanol which are reported and characterized based on
      elemental analyses, IR, solid reflectance, magnetic moment, molar conductance,
      and thermal analysis (TG). From the elemental analyses data, 1 : 2 metal
      complexes are formed having the general formulae [MCl(2)(HL)(2)] .yH(2)O (where M
      = Co(II), Ni(II), and Cu(II), y = 1-3). The important infrared (IR) spectral
      bands corresponding to the active groups in the ligand and the solid complexes
      under investigation were studied. IR spectra show that ligand is coordinated to
      the metal ions in a neutral bidentate manner with ON donor sites. The solid
      complexes have been synthesized and studied by thermogravimetric analysis. All
      the metal chelates are found to be nonelectrolytes. From the magnetic and solid
      reflectance spectra, the complexes (cobalt(II), nickel(II), and copper(II)) have
      octahedral and square planner geometry, respectively. The antibacterial and
      antifungal activity's data show that the metal complexes have a promising
      biological activity comparable with the parent ligand against bacterial and
      fungal species.

PMID- 23125561
TI  - Internet Addiction: A Brief Summary of Research and Practice.
AB  - Problematic computer use is a growing social issue which is being debated
      worldwide. Internet Addiction Disorder (IAD) ruins lives by causing neurological
      complications, psychological disturbances, and social problems. Surveys in the
      United States and Europe have indicated alarming prevalence rates between 1.5 and
      8.2% [1]. There are several reviews addressing the definition, classification,
      assessment, epidemiology, and co-morbidity of IAD [2-5], and some reviews [6-8]
      addressing the treatment of IAD. The aim of this paper is to give a preferably
      brief overview of research on IAD and theoretical considerations from a practical
      perspective based on years of daily work with clients suffering from Internet
      addiction. Furthermore, with this paper we intend to bring in practical
      experience in the debate about the eventual inclusion of IAD in the next version
      of the Diagnostic and Statistical Manual of Mental Disorders (DSM).

PMID- 23125563
TI  - TiGeS(3).
AB  - The new ternary titanium(II) thio-germanate(IV), TiGeS(3), was synthesized using
      the reactive halide flux method. The title compound shows features of a ribbon
      type structure formed from double chains composed of edge-sharing octa-hedral
      TiS(6) and pyramidal GeS(3) units, with all atoms in the asymmmetric unit
      positioned on mirror planes. While the TiS(6) octa-hedron is regular, the
      coordination around the Ge atom is rather irregular, which can be described as [3
      + 3]. Three S atoms build up a triangle that is bound to the Ge atom, the
      coordination of which is augmented by three additional S atoms at considerably
      longer distances. The charge balance can formally be described as
      [Ti(4+)][Ge(2+)][S(2-)](3).

PMID- 23125564
TI  - Redetermination of junitoite, CaZn(2)Si(2)O(7).H(2)O.
AB  - The crystal structure of the mineral junitoite, ideally CaZn(2)Si(2)O(7).H(2)O
      (calcium dizinc disilicate monohydrate), was first determined by Hamilton &
      Finney [Mineral. Mag. (1985), 49, 91-95] based on the space group Ama2, yielding
      a reliability factor R of 0.10, with isotropic displacement parameters for all
      non-H atoms. The present study reports a structure redetermination of junitoite
      using single-crystal X-ray diffraction data from a natural sample, demonstrating
      that the space group of this mineral is actually Aea2, which can be attained
      simply by shifting the origin. Topologically, the structure models in the space
      groups Aea2 and Ama2 are analogous, consisting of chains of corner-sharing ZnO(4)
      tetra-hedra parallel to the b axis, cross-linked by Si(2)O(7) tetra-hedral dimers
      (the site symmetry of the bridging O atom is ..2) along a and c, forming a three
      dimensional framework. The Ca(2+) cations (site symmetry ..2) are situated in
      cavities of the framework and are bonded to five O atoms and one H(2)O mol-ecule
      (site symmetry ..2) in a distorted octa-hedral coordination environment. However,
      some bond lengths, especially for the SiO(4) tetra-hedron, are noticeably
      different between the two structure models. Hydrogen bonding in junitoite is
      found between the water mol-ecule and a framework O atom.

PMID- 23125565
TI  - Robertsite, Ca(2)Mn(III) (3)O(2)(PO(4))(3).3H(2)O.
AB  - Robertsite, ideally Ca(2)Mn(3)O(2)(PO(4))(3).3H(2)O [calcium manganese(III) tris
      (orthophosphate) trihydrate], can be associated with the arseniosiderite
      structural group characterized by the general formula
      Ca(2)A(3)O(2)(TO(4))(3).nH(2)O, with A = Fe, Mn; T = As, P; and n = 2 or 3. In
      this study, single-crystal X-ray diffraction data were used to determine the
      robertsite structure from a twinned crystal from the type locality, the Tip Top
      mine, Custer County, South Dakota, USA, and to refine anisotropic displacement
      parameters for all atoms. The general structural feature of robertsite resembles
      that of the other two members of the arseniosiderite group, the structures of
      which have previously been reported. It is characterized by sheets of [MnO(6)]
      octa-hedra in the form of nine-membered pseudo-trigonal rings. Located at the
      center of each nine-membered ring is a PO(4) tetra-hedron, and the other eight
      PO(4) tetra-hedra sandwich the Mn-oxide sheets. The six different Ca(2+) ions are
      seven-coordinated in form of distorted penta-gonal bipyramids,
      [CaO(5)(H(2)O)(2)], if Ca-O distances less than 2.85 A are considered. Along with
      hydrogen bonding involving the water mol-ecules, they hold the manganese
      phosphate sheets together. All nine [MnO(6)] octa-hedra are distorted by the Jahn
      Teller effect.

PMID- 23125566
TI  - Caesium diuranium hexa-telluride.
AB  - Single crystals of CsU(2)Te(6) were synthesized from the reaction of U, Te, and
      Cs(2)Te(3) at 1273 K. CsU(2)Te(6) crystallizes in the space group Cmcm in the
      CsTh(2)Te(6) structure type. The asymmetric unit comprises one U (site symmetry
      m2m), one Cs (m2m; half-occupancy) and two Te atoms (m.. and m2m). The structure
      of CsU(2)Te(6) consists of infinite [U(2)Te(6)] layers perpendicular to [010]
      separated by Cs atoms. There are infinite Te-Te-Te linear chains along [001].

PMID- 23125567
TI  - Redetermination of Ba(2)CdTe(3) from single-crystal X-ray data.
AB  - The previous structure determination of the title compound, dibarium
      tritelluridocadmate, was based on powder X-ray diffraction data [Wang & DiSalvo
      (1999 ?). J. Solid State Chem.148, 464-467]. In the current redetermination from
      single-crystal X-ray data, all atoms were refined with anisotropic displacement
      parameters. The previous structure report is generally confirmed, but with some
      differences in bond lengths. Ba(2)CdTe(3) is isotypic with Ba(2)MX(3) (M = Mn,
      Cd; X = S, Se) and features (1) (infinity)[CdTe(2/2)Te(2/1)](4-) chains of corner
      sharing CdTe(4) tetra-hedra running parallel [010]. The two Ba(2+) cations are
      located between the chains, both within distorted monocapped trigonal-prismatic
      coordination polyhedra. All atoms in the structure are located on a mirror plane.

PMID- 23125568
TI  - Redetermination of clinobaryl-ite, BaBe(2)Si(2)O(7).
AB  - Clinobaryl-ite, ideally BaBe(2)Si(2)O(7) (chemical name barium diberyllium
      disilicate), is a sorosilicate mineral and dimorphic with baryl-ite. It belongs
      to a group of compounds characterized by the general formula BaM(2+)
      (2)Si(2)O(7), with M(2+) = Be, Mg, Fe, Mn, Zn, Co, or Cu, among which the Be-, Fe
      , and Cu-members have been found in nature. The crystal structure of clinobaryl
      ite has been re-examined in this study based on single-crystal X-ray diffraction
      data collected from a natural sample from the type locality (Khibiny Massif, Kola
      Peninsula, Russia). The structure of clinobaryl-ite can be considered as a
      framework of BeO(4) and SiO(4) tetra-hedra, with one of the O atoms coordinated
      to two Be and one Si, one coordinated to two Si, and two O atoms coordinated to
      one Si and one Be atom. The BeO(4) tetra-hedra share corners, forming chains
      parallel to the c axis, which are inter-linked by the Si(2)O(7) units oriented
      parallel to the a axis. The Ba(2+) cations (site symmetry m..) are in the
      framework channels and are coordinated by eleven O atoms in form of an irregular
      polyhedron. The Si-O(br) (bridging O atom, at site symmetry m..) bond length, the
      Si-O(nbr) (non-bridging O atoms) bond lengths, and the Si-O-Si angle within the
      Si(2)O(7) unit are in marked contrast to the corresponding values determined in
      the previous study [Krivovichev et al. (2004 ?). N. Jb. Miner. Mh. pp. 373-384].

PMID- 23125569
TI  - (18-Crown-6)potassium [(1,2,5,6-eta)-cyclo-octa-1,5-diene][(1,2,3,4-eta)-naph-tha
      lene]-ferrate(-I).
AB  - The title salt, [K(C(12)H(24)O(6))][Fe(C(8)H(12))(C(10)H(8))], is the only known
      naphthalene complex containing iron in a formally negative oxidation state. Each
      (naphthalene)(1,5-cod)ferrate(-I) anion is in contact with one (18-crown
      6)potassium cation via K?C contacts to the outer four carbon atoms of the
      naphthalene ligand (cod = 1,5-cyclo-octa-diene, 18-crown-6 = 1,4,7,10,13,16-hexa
      oxacyclo-octa-deca-ne). When using the midpoints of the coordinating olefin
      bonds, the overall geometry of the coordination sphere around iron can be best
      described as distorted tetra-hedral. The naphthalene fold angle between the plane
      of the iron-coordinating butadiene unit and the plane containing the exo-benzene
      moiety is 19.2 (1) degrees .

PMID- 23125570
TI  - (eta(6)-Benzene)-(benzyl-diphenyl-phos-phane)dichloridoruthenium(II).
AB  - In the title compound, [RuCl(2)(C(6)H(6))(C(19)H(17)P)], the Ru(II) atom has a
      distorted pseudo-octa-hedral coordination environment with the metrical
      parameters around the metallic core as Ru-centroid(eta(6)-benzene) = 1.6894 (11)
      A, Ru-P = 2.3466 (6), Ru-Cl(avg.) = 2.4127 (7) A; Cl-Ru-Cl = 88.07 (2) and Cl-Ru
      P = 82.77 (2), 87.65 (2) degrees . The effective cone angle for the benzyl
      diphenyl-phosphane was calculated to be 143 degrees . In the crystal C-H?Cl and C
      H?pi inter-actions are observed.

PMID- 23125571
TI  - Tetra-kis(dimethyl-ammonium) trans-di-chloridobis[5,5'-(pyrazine-2,3-diyl)bis(1H
      tetra-zol-1-ido-kappaN(1))]copper(II).
AB  - The title compound, (C(2)H(8)N)(4)[Cu(C(6)H(2)N(10))(2)Cl(2)], consists of an
      anionic complex which is composed of a Cu(II) ion surrounded by four N atoms from
      two pyrazine-2,3-diylbis(1H-tetra-zol-1-ide) ligands, and two Cl(-) atoms in a
      trans-Cl(2)N(4) coordination geometry; the Cu(II) atom lies on a site of symmetry
      2/m. The Cu-Cl distance of 2.8719 (5) A is long due to the Jahn-Teller distortion
      of the d(9) electron configuration of Cu(II) ion. The tetra-zole and pyrazine
      rings make an N-C-C-N torsion angle of 38.25 (17) degrees . The charge of the
      anionic complex is balanced by four dimethyl-ammonium cations, which inter-act
      with the anionic complexes via N-H?N and N-H?Cl hydrogen bonds.

PMID- 23125572
TI  - Bis(methanol-kappaO)bis-(1,2-diamino-2-hy-droxy-imino-ethanone oximato
      kappa(2)N,N')copper(II) bis-(oxamide dioxime) methanol disolvate.
AB  - In the title compound,
      [Cu(C(2)H(5)N(4)O(2))(2)(CH(3)OH)(2)].2C(2)H(6)N(4)O(2).2CH(3)OH, the Cu(II)
      atom, lying on an inversion center, is coordinated by four N atoms from two 1,2
      diamino-2-hy-droxy-imino-ethanone oximate anion and two O atoms from two methanol
      mol-ecules in a distorted octa-hedral geometry. The two uncoordinating oxamide
      dioxime mol-ecules, each lying on an inversion center, adopt a trans
      conformation. In the crystal, O-H?O, N-H?O and N-H?N hydrogen bonds link the
      complex mol-ecules and the oxamide dioxime and methanol mol-ecules.

PMID- 23125573
TI  - Tris(2,2'-bipyridine-kappa(2)N,N')cobalt(III) bis-[bis-(pyridine-2,6-dicarboxyl
      ato-kappa(3)O(2),N,O(6))cobaltate(III)] perchlorate dimethyl-formamide
      hemisolvate 1.3-hydrate.
AB  - In the title compound,
      [Co(C(10)H(8)N(2))(3)][Co(C(7)H(3)NO(4))(2)](2)(ClO(4)).0.5C(3)H(7)NO.1.3H(2)O,
      the Co(III) atom in the complex cation is pseudoocta-hedrally coordinated by six
      N atoms of three chelating bipyridine ligands. The Co(III) atom in the complex
      anion is coordinated by two pyridine N atoms and four carboxyl-ate O atoms of two
      doubly deprotonated pyridine-2,6-dicarboxyl-ate ligands in a distorted octa
      hedral geometry. One dimethyl-formamide solvent mol-ecule and two water mol
      ecules are half-occupied and one water mol-ecule is 0.3-occupied. O-H?O hydrogen
      bonds link the water mol-ecules, the perchlorate anions and the complex anions.
      pi-pi inter-actions between the pyridine rings of the complex anions are also
      observed [centroid-centroid distance = 3.804 (3) A].

PMID- 23125575
TI  - Poly[MU(3)-aqua-aqua(MU(3)-3,5-dinitro-benzoato-kappaO(1):O(3):O(5))caesium].
AB  - In the structure of the title complex, [Cs(C(7)H(3)N(2)O(6))(H(2)O)(2)](n), the
      Cs salt of 3,5-dinitro-benzoic acid, the metal complex centres have have
      irregular CsO(8) coordination, comprising two water mol-ecules (one triply
      bridging and the other monodentate) and four O-atom donors from two nitro groups
      and one bridging carboxyl-ate O-atom donor from the ligand. Intra-unit O-H?O
      hydrogen-bonding inter-actions involving both water mol-ecules are observed in
      the three-dimensional polymeric complex structure.

PMID- 23125574
TI  - Diaqua-tris-(nitrato-kappa(2)O,O'){2,2'-[pyridine-2,6-diylbis(methyl-ene
      oxy)]dibenzaldehyde-kappaO(1)}dysprosium(III)-2,2'-[pyridine-2,6-diylbis(methyl
      ene-oxy)]dibenzaldehyde (1/1).
AB  - The title compound, [Dy(NO(3))(3)(C(21)H(17)NO(4))(H(2)O)(2)].C(21)H(17)NO(4),
      may be considered as an organic-metalorganic 1:1 co-crystal, in which the two
      dialdehyde mol-ecules act as a ligand and as an organic moiety, respectively. The
      Dy(III) atom coordinates nine O atoms from the organic ligand, bidentate nitrate
      ions and water mol-ecules, approximating a square-face-tricapped trigonal
      prismatic geometry. The coordinated dialdehyde is not planar: the uncoordinated
      oxybenzaldehyde group is twisted by 39.96 (4) degrees  from the rest of the
      ligand. In contrast, the free organic moiety is almost planar, with an r.m.s.
      deviation of 0.15 A. In the crystal, segregated stacks of dialdehyde are formed
      in the [100] direction. For the complex, the shortest pi-pi contact is found at
      3.781 (2) A, and for the free ligand, at 3.785 (2) A. The crystal structure is
      further stabilized by O-H?O and O-H?N hydrogen bonds in which coordinated water
      mol-ecules are the donor groups.

PMID- 23125576
TI  - Guanidinium dioxidobis(picolinato-kappa(2)N,O)(picolinato-kappaO)uranate(VI).
AB  - In the title compound, (CH(6)N(3))[U(C(6)H(4)NO(2))(3)O(2)], the uranyl group is
      coordinated by two O and two N atoms from two chelating picolinate ligands, and
      one O atom from a third picolinate ligand. The coordination environment of the
      U(VI) atom (N(2)O(5)) is distorted penta-gonal-bipyramidal. In the crystal, all
      amino groups are involved in the formation of N-H?O and N-H?N hydrogen bonds,
      which link cations and anions into layers parallel to the ac plane.

PMID- 23125577
TI  - catena-Poly[[dichloridomercury(II)]-MU-{N-[(E)-pyridin-2-yl-methyl-idene
      kappaN]pyridin-3-amine-kappa(2)N(1):N(3)}].
AB  - In the title coordination polymer, [HgCl(2)(C(11)H(9)N(3))](n), the Hg(II) ion is
      coordinated by three N atoms from two N-[(E)-pyridin-2-yl-methyl-idene]pyridin-3
      amine (L) ligands and two chloride anions in a distorted trigonal-bipyramidal
      geometry. The two pyridine rings in L form a dihedral angle of 50.0 (2) degrees .
      L ligands bridge adjacent HgCl(2) units into polymeric chains propagating in
      [010]. The crystal packing is further stabilized by weak inter-molecular C-H?Cl
      hydrogen bonds and pi-pi inter-actions between the pyridine rings, with a
      centroid-centroid separation of 3.529 (9) A.

PMID- 23125578
TI  - Tetra-bromidobis(dicyclo-hexyl-phosphane-kappaP)digallium(Ga-Ga).
AB  - The title compound, a Ga(II) dimer, [Ga(2)Br(4)(C(12)H(23)P)(2)], was synthesized
      by reaction of GaBr(THF)(n) (THF is tetra-hydro-furan) with dicyclo-hexyl
      phosphine in toluene. At 150 K the crystallographically centrosymmetric molecule
      exhibits disorder in which one of the two independent cyclo-hexyl groups is
      modelled over two sites in a 62 (1):38 (1) ratio. In d(6)-benzene solution, the
      compound exhibits virtual C(2h) symmetry as determined by (1)H NMR. The
      coordination environment of the Ga(II) atom is distorted tetrahedral.

PMID- 23125579
TI  - Diaqua-bis-(1H-imidazole-4-carboxyl-ato-kappa(2)N(3),O)cobalt(II).
AB  - In the title compound, [Co(C(4)H(3)N(2)O(2))(2)(H(2)O)(2)], the Co(II) ion is
      located on a twofold rotation axis and shows a distorted octa-hedral coordination
      configuration, defined by two N,O-bidentate 1H-imidazole-4-carboxyl-ate ligands
      in the equatorial plane and two water mol-ecules in the axial positions. In the
      crystal, O-H?O and N-H?O hydrogen bonds link the mol-ecules into a three
      dimensional supra-molecular network. pi-pi stacking inter-actions between the
      imidazole rings [centroid-centroid distances = 3.4914 (15) and 3.6167 (15) A]
      further stabilize the crystal structure.

PMID- 23125580
TI  - Bis[(1,1'-biphenyl-2,2'-di-yl)di-tert-butyl-phospho-nium] di-MU-chlorido-bis
      [dichlorido-palladate(II)].
AB  - In the title compound, (C(20)H(26)P)(2)[Pd(2)Cl(6)], the Pd(II) atom within the
      hexachloridodipalladate(II) dianion has a square-planar geometry. It resides on a
      centre of inversion with the asymmetric unit containing half of the dianion and
      one phospho-nium cation. Only weak C-H?pi inter-actions are present in the
      crystal structure.

PMID- 23125581
TI  - (Naphthalene-2,3-diolato-kappa(2)O,O')[tris-(pyridin-2-ylmeth-yl)amine
      kappa(4)N]cobalt(III) tetra-phenyl-borate acetone monosolvate hemihydrate.
AB  - In the title salt,
      [Co(C(10)H(6)O(2))(C(18)H(18)N(4))](C(24)H(20)B).C(3)H(6)O.0.5H(2)O, the Co(III)
      ion in the complex cation is six-coordinated in a rigid octa-hedral N(4)O(2)
      geometry. The asymmetric unit contains one complete
      [Co(C(10)H(6)O(2))(C(18)H(18)N(4))](+) unit, one tetraphenylborate counter-anion
      and one acetone and one water mol-ecule that is located on an inversion centre.
      All the features of the Co(III) ion are fully consistent with the formulation of
      the cation as a Co(3+)-catecholate complex. Variable-temperature magnetic
      measurements in the region 2-380 K show a obvious diamagnetism over the observed
      temperature range.

PMID- 23125582
TI  - (Acetato-kappaO){bis-[(2,4-dimethyl-1H-pyrazol-1-yl)meth-yl][(pyridin-2-yl)meth
      yl]amine}-cobalt(II) hexa-fluorido-phosphate.
AB  - In the title compound, [Co(CH(3)CO(2))(C(18)H(24)N(6))]PF(6), the Co(II) atom is
      penta-coordinated in a distorted trigonal-bipyramidal geometry by four N atoms
      from a tripodal ligand and one O atom from a monodentate acetate ligand. The
      crystal packing is stabilized by inter-molecular C-H?F and C-H?O hydrogen bonds.

PMID- 23125583
TI  - Dichlorido[2-(pyridin-2-yl)-N-(pyridin-2-yl-methyl-idene)ethanamine
      kappa(3)N,N',N'']manganese(II) monohydrate.
AB  - In the title complex, [MnCl(2)(C(13)H(13)N(3))].H(2)O, the Mn(II) atom is in a
      distorted square-pyramidal environment, with an Addison tau parameter of 0.037.
      The coordination geometry is defined by three N-atom donors from the tridentate 2
      (pyridin-2-yl)-N-(pyridin-2-yl-methyl-idene)ethanamine ligand and two terminal Cl
      atoms. Although the H atoms of the lattice water molecule were not located, O?O
      distances of 3.103 (7) A and O?Cl distances of 3.240 (3) and 3.482 (4) A suggest
      that hydrogen bonding is responsible for the stabilization of the crystal
      packing.

PMID- 23125584
TI  - {4,4',6,6'-Tetrachloro-2,2'-[2,2-dimethyl-propane-1,3-diylbis(nitrilo-methanylyl
      idene)]diphenolato}dioxidomolyb-denum(VI).
AB  - The asymmetric unit of the title compound, [Mo(C(19)H(16)Cl(4)N(2)O(2))O(2)],
      comprises two independent mol-ecules (A and B). The geometry around the Mo(VI)
      atom is distorted octa-hedral in each complex mol-ecule, supported by two oxide O
      atoms and the N(2)O(2) donor atoms of the coordinating ligand. The dihedral angle
      between the benzene rings is 74.96 (11) A for mol-ecule A and 76.05 (11) A for
      mol-ecule B. In the crystal, the B mol-ecules are linked by pairs of C-H?Cl
      hydrogen bonds, forming inversion dimers. The crystal structure is further
      stabilized by C-H?pi inter-actions. An inter-esting feature of the crystal
      structure is a Cl?Cl contact [3.3748 (18) A], which is shorter than the sum of
      the van der Waals radii of Cl atoms (3.50 A).

PMID- 23125585
TI  - Bromidobis[3-(1H-pyrazol-1-yl-kappaN(2))propionamide-kappaO]copper(II) bromide
      methanol monosolvate.
AB  - The title copper(II) N-pyrazolylpropanamide (PPA) complex, [CuBr(PPA)(2)]Br, was
      obtained in 78% yield by treatment of CuBr(2) with an excess of the ligand in
      methanol. Crystallization from the mother liquid afforded the title compound,
      i.e. the methanol solvate [CuBr(C(6)H(9)N(3)O)(2)]Br.CH(3)OH or
      [CuBr(PPA)(2)]Br.MeOH, as bright green crystals. In the solid state, the title
      salt comprises isolated [CuBr(PPA)(2)](+) cations, separated bromide ions and
      methanol of crystallization. In the cation, the central Cu(II) ion is coordinated
      by two N,O-chelating PPA ligands and one Br(-) ion. The coordination geometry
      around the Cu(II) ion is distorted trigonal-bipyramidal with the bromide ligand
      and the amide O atoms occupying the equatorial positions [Cu-Br = 2.4443 (4) A;
      Cu-O = 2.035 (2) and 2.179 (2) A], while the pyrazole N atoms coordinate in the
      axial positions [Cu-N = 1.975 (2) and 1.976 (2) A]. In the crystal, the three
      constituents are linked by N-H?Br, O-H?Br, and N-H?O hydrogen bonds, forming a
      three-dimensional network.

PMID- 23125586
TI  - {4,4'-Dimeth-oxy-2,2'-[2,2-dimethyl-propane-1,3-diylbis(nitrilo-methanylyl
      idene)]diphenolato}copper(II) monohydrate.
AB  - The asymmetric unit of the title compound, [Cu(C(21)H(24)N(2)O(4))].H(2)O,
      comprises half of a Schiff base complex and a water mol-ecule. The Cu(II) atom,
      water mol-ecule and one C atom of the central propyl-ene segment are located on a
      twofold rotation axis. The geometry around the Cu(II) atom is distorted square
      planar, supported by the N(2)O(2) donor atoms of the coordinating ligand. The
      dihedral angle between the symmetry-related benzene rings is 42.56 (19) degrees .
      In the crystal, O-H?O hydrogen bonds involving the water mol-ecule make an R(2)
      (1)(6) ring motif. Complex mol-ecules are linked into a chain along the c axis
      via C-H?O inter-actions.

PMID- 23125587
TI  - Trichlorido(dimethyl sulfoxide-kappaO)(di-2-pyridyl-amine
      kappa(2)N,N')indium(III).
AB  - In the title compound, [InCl(3)(C(10)H(9)N(3))(C(2)H(6)OS)], the In(III) atom is
      six-coordinated in a distorted octa-hedral geometry by two N atoms from a
      chelating di-2-pyridyl-amine ligand, one O atom from a dimethyl sulfoxide ligand
      and three Cl atoms. Inter-molecular C-H?Cl hydrogen bonds and pi-pi contacts
      between the pyridine rings [centroid-centroid distance = 3.510 (3) A] are present
      in the crystal.

PMID- 23125588
TI  - (2.2.2-Cryptand)potassium tetra-kis-(eta(2)-ethyl-ene)cobaltate(-I).
AB  - The title salt, [K(C(18)H(36)N(2)O(6))][Co(C(2)H(4))(4)], is one of only two
      known homoleptic ethyl-enemetalates. The cation and anion are well separated,
      which gives an unperturbed tetra-hedral anion as is expected for a formally Co(
      I)d(10) metal center. The considerable elongation of the C=C bonds of the ethyl
      ene ligands [average 1.401 (6) A], relative to that of free ethyl-ene (1.333 A),
      is consistent with metal->pi* back-bonding models. One arm of the 2.2.2-cryptand
      (4,7,13,16,21,24-hexa-oxa-1,10-diaza-bicyclo-[8.8.8]hexa-cosa-ne) complexant is
      disordered and was modeled over two positions with a refined occupancy ratio of
      0.559 (2):0.441 (2). In the crystal, the cationic K(2.2.2-cryptand) units are
      linked via C-H?O hydrogen bonds, forming inversion dimers. There are no other
      significant inter-molecular inter-actions in the crystal structure.

PMID- 23125589
TI  - (2,9-Dimethyl-1,10-phenanthroline-kappa(2)N,N')bis-(thio-cyanato
      kappaS)mercury(II).
AB  - The asymmetric unit of the title compound, [Hg(SCN)(2)(C(14)H(12)N(2))], contains
      two complex mol-ecules in which the Hg(II) atoms are both four-coordinated in a
      distorted tetra-hedral configuration by two N atoms from a chelating 2,9-dimethyl
      1,10-phenanthroline ligand and by two S atoms from two thio-cyanate anions. The
      1,10-phenanthroline ligand is slightly folded for one complex, the dihedral angle
      between the pyridine planes being 5.3 (1) degrees . In contrast it is nearly
      planar [0.5 (1) degrees ] as it complexes with the other Hg(II) atom. The thio
      cyanate ligands are virtually linear and the S atom is bonded to Hg(II) with N?S
      Hg angles ranging from 99.3 (1) to 103.5 (1) degrees . Despite the presence of
      six aromatic rings in the asymmetric unit, there are no significant inter
      molecular pi-pi contacts between phenanthroline ligands as the centroid-centroid
      distance of the closest contact between six-membered rings is 4.11 (1) A degrees
      .

PMID- 23125591
TI  - (2.2.2-Cryptand)potassium bis-(cyanato-kappaN)(5,10,15,20-tetra-phenyl-por-phy
      rin-ato-kappa(4)N)cobaltate(III) chloro-benzene hemisolvate.
AB  - In the title compound,
      [K(C(18)H(36)N(2)O(6))][Co(NCO)(2)(C(44)H(28)N(4))].0.5C(6)H(5)Cl or [K(2,2,2
      crypt)(+)][Co(III)(NCO)(2)(TPP)(-)].0.5C(6)H(5)Cl, the Co(III) ion is octa
      hedrally coordin-ated by two axial N-bonded NCO(-) anions and four pyrrole N
      atoms of the porphyrin. There is a major ruffling distortion of the porphyrin:
      the dihedral angles between trans pyrrole rings are 34.32 (14) and 34.72 (14)
      degrees . The potassium ion is coordinated by the six O atoms and two N atoms of
      the cryptand-222 mol-ecule and a weak K-O [3.407 (3) A] bond to one of the
      cyanate O atoms also occurs. The packing also features weak C-H?O and C-H?pi
      inter-actions. The contribution to the scattering of the disordered chloro
      benzene solvent mol-ecules was removed with the SQUEEZE function in PLATON [Spek
      (2009 ?). Acta Cryst. D65, 148-155].

PMID- 23125590
TI  - (Acetato-kappa(2)O,O')(acetato-kappaO)bis(2-amino-3-methyl-pyridine
      kappaN(1))cobalt(II).
AB  - In the title compound, [Co(CH(3)COO)(2)(C(6)H(8)N(2))(2)], the Co(II) ion is five
      coordinated by two pyridine N atoms from two 2-amino-3-methyl-pyridine ligands,
      two O atoms from one acetate ion and one O atom from another acetate ion in a
      distorted trigonal-bipyramidal geometry. The pyridine rings are nearly
      perpendicular to each other [dihedral angle = 84.49 (16) degrees ]. The crystal
      packing is stabilized by intra-molecular and inter-molecular N-H?O hydrogen
      bonding inter-actions.

PMID- 23125592
TI  - Bis(MU-4,4''-difluoro-1,1':3',1''-terphenyl-2'-carboxylato
      kappa(2)O:O')bis[aqua(4,4''-di-fluoro-1,1':3',1''-terphenyl-2'-carboxyl-ato
      kappaO)(pyridine-kappaN)cobalt(II)] diethyl ether disolvate.
AB  - The structure of the title compound,
      [Co(2)(C(19)H(11)F(2)O(2))(4)(C(5)H(5)N)(2)(H(2)O)(2)].2C(4)H(10)O, comprises two
      Co(II) atoms in a distorted square pyramidal coordination environment, straddling
      a crystallographic inversion center with a Co?Co separation of 3.1923 (15) A.
      Each Co(2+) cation is coordinated by three O atoms of three 4,4''-difluoro
      1,1':3',1''-terphenyl-2'-carboxyl-ate ligands, one water O atom and one pyridine
      N atom, forming a CoO(4)N polyhedron. Strong intra-molecular O-H?O hydrogen bonds
      are observed between terminal metal-bound carboxyl-ate groups and water O atoms.

PMID- 23125593
TI  - Tetra-kis(MU(2)-cyanido-kappa(2)C:N)dicyanido-tetra-kis-[tris-(2-amino-eth
      yl)amine-kappa(3)N,N',N'',N''']tetra-copper(II)iron(II)
      bis[pentacyanidonitrosoferrate(II)] hexahydrate.
AB  - The asymmetric unit of the title complex,
      [Cu(4)Fe(CN)(6)(C(6)H(18)N(4))(4)][Fe(CN)(5)(NO)](2).6H(2)O, comprises a complex
      [{Cu(tren)CN}(4)Fe(CN)(2)](4+) [tren is tris-(2-amino-eth-yl)amine] cation, which
      exhibits -1 symmetry with the terminal cyanide ligands oriented trans to each
      other, and two [Fe(CN)(5)(NO)](2-) nitroprussiate counter-anions. In the crystal,
      N-H?N hydrogen-bonding inter-actions are observed between H atoms on the primary
      amine groups of the tren ligand and the terminal cyanide groups of the nitro
      prussiate counter-ions. The N atom in the terminal CN ligand of the cation is
      equally disordered over two positions. The structure also contains disordered
      lattice water mol-ecules. Their contribution was elimin-ated from the refinement
      using the procedure described by van der Sluis & Spek (1990 ?).

PMID- 23125594
TI  - Poly[diammonium [(MU(4)-butane-1,2,3,4-tetra-carboxyl-ato)zincate] tetra
      hydrate].
AB  - In the title compound, {(NH(4))(2)[Zn(C(8)H(6)O(8))].4H(2)O}(n), the asymmetric
      unit contains one ammonium cation, half of a butane-1,2,3,4-tetra-carboxyl-ate
      anion, one Zn(2+) cation and two water mol-ecules. The butane-1,2,3,4-tetra
      carboxyl-ate ligand is located about an inversion centre at the mid-point of the
      central C-C bond. The Zn(2+) cation is situated on a twofold rotation axis and is
      surrounded by four O atoms from four symmetry-related butane-1,2,3,4-tetra
      carboxyl-ate anions in a distorted tetra-hedral environment. In turn, each anion
      coordinates to four Zn(2+) cations. The bridging mode of the anions leads to a
      three-dimensional framework structure with channels extending along [110] and
      [010] in which the ammonium cations and the water mol-ecules are located. N-H?O
      and O-H?O hydrogen bonding between the cations and water mol-ecules and the
      uncoordinating O atoms of the carboxyl-ate groups consolidates the crystal
      packing.

PMID- 23125595
TI  - Poly[hexa-aqua-bis-(MU(4)-pyrimidine-4,6-dicarboxyl-ato)tetra-lithium].
AB  - The asymmetric unit of the title compound,
      [Li(4)(C(6)H(2)N(2)O(4))(2)(H(2)O)(6)](n), comprises two Li(+) ions bridged by a
      completely deprotonated pyrimidine-3,6-dicarboxyl-ate ligand and coordinated by
      two water mol-ecules; the asymmetric units related by an inversion operation
      create a structural unit which forms part of a two-dimensional polymeric
      structure parallel to (10-1). One of the Li(+) ions shows a distorted tetra
      hedral arrangement involving two symmetry-related coordinating water mol-ecules
      and two carboxyl-ate O atoms. The other Li(+) ion is in distorted trigonal
      bipyramidal geometry defined by N and O atoms of the ligands and a water mol
      ecule. Water O atoms are proton donors to carboxyl-ate O atoms forming hydrogen
      bonds.

PMID- 23125596
TI  - Bis[4-amino-3,5-bis-(pyridin-2-yl)-4H-1,2,4-triazole-kappa(2)N(1),N(5)]diaqua
      cobalt(II) bis-(perchlorate).
AB  - In the title structure, [Co(C(12)H(10)N(6))(2)(H(2)O)(2)](ClO(4))(2), the Co(II)
      atom lies on an inversion centre and is coordinated in a slightly distorted octa
      hedral geometry by four N atoms from two 4-amino-3,5-bis-(pyridin-2-yl)-4H-1,2,4
      triazole (adpt) ligands in equatorial positions and two O atoms from two water
      mol-ecules in axial positions. An intra-molecular N-H?N inter-action stabilizes
      the mol-ecular conformation. Inter-molecular N-H?O and O-H?O inter-actions
      involving the perchlorate counter-anions extend the monomeric compound into a two
      dimensional network parallel to the bc plane.

PMID- 23125597
TI  - 3-(Ferrocen-1-ylcarbon-yl)-1-methyl-4-(4-methyl-phen-yl)spiro-[pyrrolidine-2,11'
      indeno-[1,2-b]quinoxaline].
AB  - In the title compound, [Fe(C(5)H(5))(C(32)H(26)N(3)O)], the pyrrolidine ring
      adopts a twist conformation. The indeno-quinoxaline ring system [86.44 (5)
      degrees ], the methyl-phenyl ring [86.06 (7) degrees ] and the ferrocene rings
      [82.00 (7) and 83.95 (9) degrees ] are almost perpendicular to the pyrrolidine
      ring. The two cyclopentadienyl rings adopt an eclipsed conformation. The crystal
      structure features C-H?N inter-actions.

PMID- 23125598
TI  - (MU-3,5,9,11-Tetra-oxo-4,10-diaza-tetra-cyclo-[5.5.2.0(2,6).0(8,12)]tetra-dec-13
      ene-4,10-diido-kappa(2)N:N')bis-[(2,2'-bipyridine-kappa(2)N,N')silver(I)]
      dihydrate.
AB  - In the title complex, [Ag(2)(C(12)H(8)N(2)O(4))(C(10)H(8)N(2))(2)].2H(2)O, the
      Ag(I) ion is three-coordinated by two N atoms from a chelating 2,2'-bipyridine
      ligand and one N atom from an imide ligand in a Y-shaped fashion. The imide
      ligand and the complex lie on a twofold rotation axis. The ligand bridges two
      Ag(I) ions, forming a dinuclear complex. In the crystal, O-H?O hydrogen bonds
      link the lattice water mol-ecules and the complex mol-ecules into a ribbon-like
      structure along [001]. pi-pi inter-actions are observed between the pyridine
      rings [centroid-centroid distance = 3.8289 (14) A].

PMID- 23125599
TI  - Poly[(MU(4)-biphenyl-2,4'-dicarboxyl-ato
      kappa(5)O(2):O(2'):O(4):O(4),O(4'))zinc].
AB  - The crystal structure of the polymeric title complex, [Zn(C(14)H(8)O(4))](n), is
      composed of layers parallel to (110) formed by linking of Zn-carboxyl-ate chains
      with biphenyl units of the biphenyl-2,4'-dicarboxyl-ate (bpdc) ligands. The
      Zn(II) atom is five-coordinated in a distorted square-pyramidal geometry by five
      O atoms from four bpdc ligands. The dihedral angle between the benzene rings is
      52.32 (12) degrees .

PMID- 23125600
TI  - catena-Poly[[[iodidocopper(I)]-{MU-N-[(pyridin-2-yl-kappaN)methyl-idene]pyridin-3
      amine-kappa(2)N(3):N(1)}] acetonitrile hemisolvate].
AB  - In the asymmetric unit of the title polymeric complex,
      {[CuI(C(11)H(9)N(3))].0.5CH(3)CN}(n), there are two Cu(I) atoms, two N-[(pyridin
      2-yl-kappaN)methyl-idene]pyridin-3-amine (PyPy) ligands and two I atoms. Both
      Cu(I) atoms have a distorted tetra-hedral geometry, each being coordinated by one
      I atom, two N atoms of one PyPy ligand and one N atom from an adjacent PyPy
      ligand. In the crystal, infinite helical chains of [Cu(2)(PyPy)(2)](n) are formed
      propagating along the b axis. These chains are linked via weak C-H?I hydrogen
      bonds and pi-pi stacking inter-actions [shortest centroid-centroid distance =
      3.2727 (14) A]. During the refinement, electron-density peaks were located that
      were believed to be highly disordered solvent mol-ecules (possibly acetonitrile).
      The SQUEEZE option in PLATON [Spek (2009 ?). Acta Cryst. D65, 148-155] indicated
      there were solvent cavities with a total volume of 196 A(3) containing
      approximately 60 electrons per unit cell, which equated to one mol-ecule of
      acetonitrile per asymmetric unit.

PMID- 23125601
TI  - Trimethyl-ammonium dichlorido-triphenyl-stannate(IV).
AB  - In the structure of the title monomeric coordination salt,
      (C(3)H(10)N)[Sn(C(6)H(5))(3)Cl(2)], the Sn(IV) atom is five coordinate, with the
      SnC(3)Cl(2) entity in a trans trigonal-bipyramidal arrangement and the chlorine
      atoms in apical positions. In the crystal, the cations and anions are connected
      by N-H?Cl hydrogen bonds.

PMID- 23125602
TI  - Two coordination modes of Cu(II) in a binuclear complex with N-(pyridin-2-yl
      carbon-yl)pyridine-2-carboxamidate ligands.
AB  - In the title dinuclear complex, (acetonitrile-1kappaN)[MU-N-(pyri-din-2
      ylcarbonyl)pyridine-2-carboxamidato-1:2kappa(5)N,N',N'':O,O'][N-(pyridin-2
      ylcarbonyl)pyridine-2-carboxamidato
      2kappa(3)N,N',N'']bis(trifluoromethanesulfonato-1kappaO)dicopper(II),
      [Cu(2)(C(12)H(8)N(3)O(2))(2)(CF(3)O(3)S)(2)(CH(3)CN)], one of the Cu(II) ions is
      five-coordinated in a distorted square-pyramidal N(3)O(2) environment provided by
      two N-(pyridin-2-ylcarbon-yl)pyridine-2-carboxamidate (bpca) ligands, while the
      second Cu(II) ion is six-coordinated in a distorted octa-hedral N(4)O(2)
      environment provided by one bpca ligand, two trifluoro-methansulfonate ligands
      and one acetonitrile mol-ecule. Weak inter-molecular C-H?O and C-H?F hydrogen
      bonds and pi-pi stacking inter-actions with centroid-centroid distances of 3.6799
      (15) and 3.8520 (16) A stabilize the crystal packing and lead to a three
      dimensional network.

PMID- 23125603
TI  - {2,6-Bis[(2,6-diisopropyl-phosphan-yl)-oxy]-4-fluoro-phenyl-kappa(3)P,C(1),P'}(1H
      pyrazole-kappaN(2))nickel(II) hexa-fluoro-phosphate.
AB  - The title compound, [Ni(C(18)H(30)FO(2)P(2))(C(3)H(4)N(2))]PF(6), was prepared by
      halide abstraction with TlPF(6) in the presence of CH(3)CN in CDCl(3) from the
      respective neutral pincer chlorido analogue followed by addition of pyrazole. The
      PO-C-OP pincer ligand acts in typical trans-P(2) tridentate fashion to generate a
      distorted square-planar nickel structure. The Ni-N(pyrazole) distance is 1.925
      (2) A and the plane of the pyrazole ligand is rotated 56.2 (1) degrees  relative
      to the approximate square plane surrounding the Ni(II) center in which the
      pyrazole is bound to the Ni(II) atom through its sp(2)-hybridized N atom. This Ni
      N distance is similar to bond lengths in the other reported Ni(II) pincer-ligand
      square-planar pyrazole complex structures; however, its dihedral angle is
      significantly larger than any of those for the latter set of pyrazole complexes.

PMID- 23125604
TI  - Dibutyl-ammonium bis-(hydrogen methylphosphonato-kappaO)triphenylstannate(IV).
AB  - The asymmetric unit of the title organotin salt,
      (C(8)H(20)N)[Sn(C(6)H(5))(3)(CH(4)O(3)P)(2)], contains two dibutyl-ammonium
      cations and two stannate(IV) anions consisting each of two monodentately bonding
      methyl hydrogenphosphate groups attached to an Sn(C(6)H(5)) unit. The overall
      coordination environment of the two Sn(IV) atoms is trigonal-bipyramidal defined
      by three phenyl C atoms in equatorial positions and two methyl hydrogenphosphate
      O atoms at the apical sites. In the crystal, the stannate(IV) anions are linked
      to each other via pairs of short O-H?O hydrogen bonds, leading to an infinite
      chain extending parallel to the b-axis direction. Neighbouring chains are linked
      by N-H?O hydrogen bonds involving the butyl-ammonium cations, giving a two
      dimensional structure parallel to the ab plane. The crystal under investigation
      was found to be twinned by reticular merohedry with twin fractions of 0.5342
      (7):0.4658 (7).

PMID- 23125605
TI  - Poly[diaqua-[MU-1,4-bis-(1H-imidazol-1-yl)benzene-kappa(2)N(3):N(3')](MU-fumarato
      kappa(2)O(1):O(4))nickel(II)].
AB  - In the title compound, [Ni(C(4)H(2)O(4))(C(12)H(10)N(4))(H(2)O)(2)](n), the
      Ni(II) ion has a distorted octa-hedral coordination geometry. The asymmetric unit
      is composed of an Ni(2+) ion, located on a twofold rotation axis, one half of a
      1,4-bis-(1H-imidazol-1-yl)benzene (BIMB) ligand and one half of a fumarte (fum(2
      )) dianion, both ligands being located about inversion centers, and a
      coordinating water mol-ecule. The Ni(II) ions are linked by two BIMB ligands and
      two fum(2-) dianions, forming a four-connected layered structure parallel to
      (010) with a 4(4)-sql topology. Within each layer, there are rhombic grids with
      dimensions of ca 13.5 * 9.0 A and approximate angles of 109 and 70 degrees . The
      crystal packing features a two-dimensional -> two-dimensional parallel/parallel
      interpenetration in which one undulating layer is catenated to another equivalent
      one, forming a new bilayer. Moreover, the entangled two-dimensional layers are
      connected by O-H?O and C-H?O hydrogen bonds, generating a three-dimensional
      structure.

PMID- 23125606
TI  - Bis(1H-benzimidazole-2-carboxyl-ato-kappa(2)N(3),O)bis-(ethanol
      kappaO)manganese(II).
AB  - In the title compound, [Mn(C(8)H(5)N(2)O(2))(2)(C(2)H(5)OH)(2)], the Mn(II) atom
      is six-coordinated by two N and two O atoms from two 1H-benzimidazole-2-carboxyl
      ate (L) ligands and by two O atoms from two ethanol mol-ecules in a distorted
      octa-hedral geometry. The mean planes of the two L ligands are inclined to each
      other at 7.6 (1) degrees . In the crystal, N-H?O and O-H?O hydrogen bonds link
      the mol-ecules into layers parallel to the ab plane.

PMID- 23125607
TI  - Poly[[MU(2)-1,4-bis-(imidazol-1-ylmethyl)-benzene](MU(4)-3,5,9,11-tetra-oxo-4,10
      diaza-tetra-cyclo-[5.5.2.0(2,6).0(8,12)]tetra-dec-13-ene-4,10-diido)disilver(I)].
AB  - In the title complex, [Ag(2)(C(12)H(8)N(2)O(4))(C(14)H(14)N(4))](n), one Ag(I)
      ion, lying on a twofold rotation axis, is coordinated by two N atoms from two
      3,5,9,11-tetra-oxo-4,10-diaza-tetra-cyclo-[5.5.2.0(2,6).0(8,12)]tetra-dec-13-ene
      4,10-diide (L) ligands in a nearly linear arrangement. The other Ag(I) ion, lying
      on an inversion center, is coordinated by two O atoms from two L ligands and two
      N atoms from two 1,4-bis-(imidazol-1-ylmeth-yl)benzene ligands in a distorted
      square-planar geometry. An additional Ag?Ag [3.0119 (3) A] inter-action links the
      Ag(I) ions into a chain along [010]. The two types of ligands have mirror
      symmetry and connect the Ag(I) ions into a layer parallel to (100).

PMID- 23125608
TI  - Poly[tetra-kis-(dimethyl-formamide)tris(MU(4)-terephthalato)trimagnesium].
AB  - The title framework compound, [Mg(3)(C(8)H(4)O(4))(3)(C(3)H(7)NO)(4)](n) or
      [Mg(3)(bdc)(3)(DMF)(4)](n), was obtained as a side product of the solvothermal
      reaction of magnesium nitrate, terephthalic acid (bdcH(2)), and 1,3-bis-(4-pyrid
      yl)propane in a 1:2:1 ratio in dimethyl-formamide (DMF). The asymmetric unit
      consists of three Mg(II) cations, three terephthalate anions, and four
      coordinating DMF mol-ecules. One of the four DMF mol-ecules was refined as
      disordered over two mutually exclusive positions, with an occupancy rate for the
      major moiety of 0.923 (4). The three Mg(II) cations possess distorted octa-hedral
      coordination geometries that form linear Mg trimers. Of the three Mg(II) cations,
      the central Mg(II) is octa-hedrally coordinated by six different carboxyl-ate O
      atoms. The terminal Mg(II) cations are bonded to four O atoms of three bdc
      linkers and to two O atoms of coordinating DMF mol-ecules. The compound has a two
      dimensional 3(6)-network structure parallel to (001) that is formed by connection
      of the Mg trimers as distorted octa-hedral nodes to the bdc ligands as linkers.

PMID- 23125610
TI  - Di-MU-chlorido-bis-{chlorido[2,3-dimethyl-N-(pyridin-2-yl-methyl-idene)aniline
      kappa(2)N,N']mercury(II)}.
AB  - In the centrosymmetric binuclear molecule of the title complex,
      [Hg(2)Cl(4)(C(14)H(14)N(2))(2)], the five-coordinated Hg(II) ions have a
      distorted square-pyramidal geometry defined by two N atoms belonging to the
      chelating imino-pyridine ligand and three Cl atoms. The benzene and pyridine
      rings are oriented at a dihedral angle of 56.7 (6) degrees . The crystal packing
      is stabilized by C-H?Cl hydrogen bonds and pi-pi inter-actions between the
      pyridine rings [centroid-centroid distance = 3.796 (6) A].

PMID- 23125609
TI  - Octa-carbonyldi-MU(2)-hydrido-[MU(3)-(1,3,5-trimethyl-phen-yl)phosphinidene](tri
      phenyl-phosphane)-triangulo-triruthenium.
AB  - In the crystal structure of the title compound,
      [Ru(3)(C(9)H(11)P)H(2)(C(18)H(15)P)(CO)(8)], the triangular Ru(3) unit is capped
      with one mesitylphosphin-idene ligand. In the trigonal-pyramidal Ru(3)P core, one
      Ru(II) atom is coordinated by a triphenyl-phosphane ligand in a terminal fashion.
      Two hydride ligands bridge over two Ru-Ru bonds. These Ru-Ru bonds [2.9400 (4)
      and 2.9432 (4) A] are slightly longer than the nonhydride-bridged Ru-Ru bond
      [2.8146 (4) A]. The terminal triphenyl-phosphane ligand coordinates to the Ru(II)
      atom, which is involved in two hydride bridges.

PMID- 23125611
TI  - Iodido[5-methyl-1H-benzimidazole-2(3H)-thione-kappaS]bis-(triphenyl-phosphane
      kappaP)copper(I) methanol monosolvate.
AB  - In the title compound, [CuI(C(8)H(8)N(2)S)(C(18)H(15)P)(2)].CH(3)OH, the
      coordination environment around the Cu(I) atom is distorted tetra-hedral, defined
      by two P atoms of two triphenyl-phosphane ligands, one S atom of a 5-methyl-1H
      benzimidazole-2(3H)-thione ligand and one I atom. The complex mol-ecules and the
      methanol solvent mol-ecules are connected via N-H?O and O-H?I hydrogen bonds,
      forming a chain along [010]. An intra-molecular N-H?I hydrogen bond is also
      observed.

PMID- 23125612
TI  - Tetra-kis(MU-2-phenyl-quinoline-4-carboxyl-ato-kappa(2)O:O')bis-[(methanol
      kappaO)copper(II)].
AB  - The title complex, [Cu(2)(C(16)H(10)NO(2))(4)(CH(3)OH)(2)], consists of
      centrosymmetric wheel-shaped dinuclear neutral mol-ecules in which each Cu(II)
      atom is coordinated in a slightly distorted square-pyramidal geometry by four O
      atoms of carboxyl-ate groups from different ligands at the basal plane and an O
      atom of a methanol mol-ecule at the axial position. In the crystal, the dinuclear
      complex mol-ecules are linked into one-dimensional supra-molecular columns
      parallel to the b axis by O-H?N hydrogen bonds and pi-pi stacking inter-actions
      [centroid-centroid distance = 3.7259 (11) A].

PMID- 23125613
TI  - Dioxido{4,4',6,6'-tetrabromo-2,2'-[2,2-dimethylpropane-1,3
      diylbis(nitrilomethanylylidene)]diphenolato}molyb-denum(VI).
AB  - The asymmetric unit of the title compound, [Mo(C(19)H(16)Br(4)N(2)O(2))O(2)],
      comprises two mol-ecules. The coordination environments around the Mo(VI) atoms
      are distorted octa-hedral, defined by two oxide ligands and an N(2)O(2) donor set
      of the tetra-dentate Schiff base in each mol-ecule. The dihedral angles between
      the benzene rings in the mol-ecules are 76.2 (3) and 77.7 (3) degrees . An inter
      esting feature of the crystal structure is the presence of Br?Br contacts [3.4407
      (11), 3.5430 (11) and 3.6492 (10) A], which are shorter than the sum of the van
      der Waals radius of Br atoms (3.70 A). The crystal structure is further
      stabilized by inter-molcular C-H?Br and C-H?pi inter-actions. The crystal under
      investigation was twinned by nonmerohedry in a 0.053 (1):0.947 (1) ratio.

PMID- 23125614
TI  - catena-Poly[[[bis-(thio-cyanato-kappaN)zinc]bis-[MU-1,3,5-tris-(1H-1,2,4-triazol
      1-yl-meth-yl)benzene-kappa(2)N(4):N(4')]] mono-hydrate].
AB  - In the title complex, {[Zn(NCS)(2)(C(15)H(15)N(9))(2)].H(2)O}(n), the Zn(II) ion
      is located on an inversion centre and is six-coordinated in a distorted octa
      hedral geometry, coordinated by N atoms from four bridging 1,3,5-tris-(1,2,4
      triazol-1-ylmeth-yl)benzene (ttmb) ligands and two terminal SCN(-) counter
      anions. Two of the three triazol groups in each ttmb ligand link the Zn(II)
      atoms, forming a looped-chain structure along [0-11]. The lattice water molecule
      shows half-occupancy due to disorder around an inversion centre.

PMID- 23125615
TI  - Di-MU-chlorido-bis-[(2-amino-4-methyl-pyridine-kappaN)-chloridomercury(II)].
AB  - In the centrosymmetric dinuclear title compound, [Hg(2)Cl(4)(C(6)H(8)N(2))(2)],
      the Hg(II) ion is four-coordinated by one pyridine N atom from a 2-amino-4-methyl
      pyridine ligand, one terminal Cl atom and two bridging Cl atoms. A distorted
      tetra-hedral geometry is formed around each Hg(II) ion. The crystal packing is
      stabilized by intra- and inter-molecular N-H?Cl hydrogen bonding. There are also
      pi-pi stacking inter-actions in the structure, with centroid-to-centroid
      distances of 3.594 (6) A.

PMID- 23125616
TI  - (1-{(E)-[Phen-yl(pyridin-2-yl-kappaN)methyl-idene]amino-kappaN}pyrrolidin-2-one
      kappaO)bis-(thio-cyanato-kappaN)copper(II).
AB  - The Cu(II) atom in the title compound, [Cu(NCS)(2)(C(16)H(15)N(3)O)], is bonded
      to the N atoms of two thio-cyanate ions, and is N,N'-chelated by the Schiff base
      ligand. The four N atoms surround the metal atom to form a distorted square; the
      square environment is distorted towards a square pyramid by a long Cu?O inter
      action. In the crystal, two C atoms of the pyrrolidin-2-one ring are disordered
      over two positions in a 1:1 ratio.

PMID- 23125617
TI  - Poly[MU-aqua-diaquabis-[MU-2-cyano-2-(oxidoimino)-acetato]
      copper(II)dipotassium].
AB  - In the title compound, [CuK(2)(C(3)N(2)O(3))(2)(H(2)O)(3)](n), the Cu(2+) atom is
      in a distorted square-pyramidal coordination geometry. Two N atoms belonging to
      the oxime groups and two O atoms belonging to the carboxyl-ate groups of two
      trans-disposed doubly deprotonated residues of 2-cyano-2-(hy-droxy-imino)-acetic
      acid make up the basal plane and the apical position is occupied by the water mol
      ecule. The neighboring Cu-containing moieties are linked into a three-dimensional
      framework by K-O and K-N contacts formed by two potassium cations with the
      carboxyl-ate and the oxime O atoms and the nitrile N atoms of the ligand. The
      environments of the K(+) cations are complemented to octa- and nona-coordinated,
      by K-O contacts with H(2)O mol-ecules. The crystal structure features O-H?O
      hydrogen bonds.

PMID- 23125618
TI  - Bis(MU-3-carb-oxy-2-hy-droxy-propane-1,2-dicarboxyl-ato)bis(diaquazinc)-1,2-bis
      (pyridin-4-yl)ethene-water (1/1/2).
AB  - The asymmetric unit of the title compound,
      [Zn(2)(C(6)H(6)O(7))(2)(H(2)O)(4)].C(12)H(10)N(2).2H(2)O, comprises half of a
      centrosymmetric complex dimer, half of a 1,2-bis-(pyridin-4-yl)ethene mol-ecule,
      which lies across an inversion centre, and one lattice water mol-ecule. Carboxyl
      ate groups of two dianionic citrate ligands bridge two Zn(II) ions to give the
      cyclic dimer, with each Zn(II) ion coordinated by four O atoms from the chelating
      citrate ligand (one hy-droxy and three carboxyl-ate, with one bridging) and two
      water O atoms, forming a distorted octa-hedral environment [Zn-O = 2.040 (3)
      2.244 (3) A]. In the crystal, O-H?O and O-H?N hydrogen bonds involving hy-droxy
      groups and both coordinating and lattice water mol-ecules link the dimers to give
      a three-dimensional framework structure.

PMID- 23125619
TI  - Poly[[diaqua-(MU-4,4'-bipyridine N,N'-di-oxide-kappa(2)O:O')(MU-terephthalato
      kappa(2)O(1):O(4))cobalt(II)] 4,4'-bipyridine N,N'-dioxide monosolvate].
AB  - In the title compound,
      {[Co(C(8)H(4)O(4))(C(10)H(8)N(2)O(2))(H(2)O)(2)].C(10)H(8)N(2)O(2)}(n), the
      Co(II) atom, lying on an inversion center, is hexa-coordinated in a distorted
      octa-hedral geometry defined by two O atoms from two terephthalate (tp) ligands,
      two O atoms from two 4,4'-bipyridine N,N'-dioxide (bpydo) ligands and two water
      mol-ecules. The coordinated tp and bpydo ligands and uncoordinated bpydo mol
      ecule all have an inversion center. The Co(II) atoms are connected by the tp and
      bpydo ligands into a layer parallel to (111). In the crystal, O-H?O hydrogen
      bonds link the uncoordinated bpydo mol-ecules and the layers into a three
      dimensional supra-molecular structure. Intra-layer O-H?O hydrogen bonds and pi-pi
      inter-actions [centroid-to-centroid distances = 3.6643 (13) and 3.8048 (13) A]
      are also observed.

PMID- 23125620
TI  - (Acetato-kappa(2)O,O')[2'-(di-tert-butyl-phosphanyl)-1,1'-biphenyl
      kappa(2)P,C(2)]palladium(II).
AB  - The structure of the title compound, [Pd(C(2)H(3)O(2))(C(20)H(26)P)], shows a
      distorted square-planar geometry for the Pd(II) atom, with significant deviations
      being evident owing to the asymmetric coordination mode of the acetate ligand. A
      weak intra-molecular C-H?O inter-action is noted. The crystal studied was a
      racemic twin.

PMID- 23125621
TI  - (2-Ethyl-2-oxazoline-kappaN)bis(N-ethyl-N-phenyl-dithio-carbamato
      kappa(2)S,S')cadmium.
AB  - In the title compound, [Cd(C(9)H(10)NS(2))(2)(C(5)H(9)NO)], the Cd(II) atom is
      five-coordinated in a distorted square-pyramidal geometry by four S atoms from
      two chelating N-ethyl-N-phenyl dithio-carbamate ligands and one N atom from a 2
      ethyl-2-oxazoline ligand. Inter-molecular C-H?pi inter-actions are observed in
      the crystal structure.

PMID- 23125622
TI  - MU-Oxalato-kappa(4)O(1),O(2):O(1'),O(2')-bis-[aqua-(2,2'-bipyridine
      kappaN)(nitrato-kappa(2)O,O')lead(II)].
AB  - The title compound, [Pb(2)(C(2)O(4))(NO(3))(2)(C(10)H(8)N(2))(2)(H(2)O)(2)], was
      synthesized hydro-thermally. The binuclear complex mol-ecule is centrosymmetric,
      the inversion centre being located at the mid-point of the oxalate C-C bond. The
      Pb(II) ion is hepta-coordinated by the O atom of one water mol-ecule, two oxalate
      O atoms, two nitrate O atoms and two 2,2'-bipyridine N atoms, forming an
      irregular coordination environemnt. Inter-molecular O-H?O hydrogen bonds between
      water mol-ecules and oxalate and nitrate ions result in the formation of layers
      parallel to (010). pi-pi inter-actions between pyridine rings in adjacent layers,
      with centroid-centroid distances of 3.584 (2) A, stabilize the structural set-up.

PMID- 23125624
TI  - Tris(eta(5)-cyclo-penta-dien-yl)-tris-[eta(6)-[9,10-dihydro-anthracene-9,10-endo
      3',4'-(N-benz-yl)pyrrolidine]]triruthenium(II) tris-(hexa-fluoro-phosphate)
      acetone disolvate.
AB  - In the title compound, [Ru(3)(C(25)H(23)N)(C(5)H(5))(3)].3PF(6).2C(3)H(6)O], the
      cation is a triruthenium complex of a 9,10-dihydro-anthracene derivative. Three
      RuCp(+) (Cp is cyclo-penta-dien-yl) groups are bonded to the three aromatic rings
      of the ligand. Surprisingly, the pyramidalized N atom of the heterocycle (Sigma C
      N-C = 329.0 degrees ) points towards the anthracenyl group, so losing its
      coordinative ability. There is an inter-molecular C-H?pi inter-action involving
      an acetone mol-ecule and the adjacent benzyl ring of the ligand. In the crystal,
      mol-ecules are linked via a number of C-H?O and C-H?F inter-actions and a C-H?pi
      inter-action, leading to the formation of a three-dimensional supra-molecular
      structure. One of the Cp groups is disordered over two positions, with refined
      occupancies of 0.695 (14):0.305 (14). Two of the three hexa-fluoro-phospate
      anions are disordered, with refined occupancies of 0.630 (6):0.370 (6) and 0.771
      (8):0.229 (8). One of the two solvent acetone mol-ecules is also disordered, with
      refined occupancies of 0.82 (2):0.18 (2).

PMID- 23125623
TI  - cis-Chloridobis(4,4'-dimethyl-2,2'-bipyridine-kappa(2)N,N')oxidovanadium(IV)
      chloride ethanol monosolvate monohydrate.
AB  - In the title compound, [VClO(C(12)H(12)N(2))(2)]Cl.C(2)H(5)OH.H(2)O, the V(IV)
      atom is six-coordinated in a distorted octa-hedral geometry by four N atoms from
      two 4,4'-dimethyl-2,2'-bipyridine ligands, one O atom and one Cl atom. In the
      crystal, O-H?Cl, C-H?O and C-H?Cl hydrogen bonds and pi-pi contacts between the
      pyridine rings [centroid-centroid distances = 3.7236 (17) and 3.6026 (19) A]
      stabilize the structure. Intra-molecular C-H?O and C-H?Cl hydrogen bonds are also
      present.

PMID- 23125625
TI  - catena-Poly[(MU-anilido)(MU-1,2-dimeth-oxy-ethane-kappa(3)-O,O':O)sodium].
AB  - In the title compound, [Na(C(6)H(5)NH)(C(4)H(10)O(2))], the Na(+) cation is
      coordinated by the N atoms of two anilide anions, two O atoms of a chelating 1,2
      dimeth-oxy-ethane (dme) ligand and one O atom of an adjacent dme ligand. The
      coordination polyhedron around Na(+) corresponds to a distorted square pyramid
      with the N atoms of the anilide groups and the O atoms of the chelating dme unit
      at the base and a third O atom at the apical position. The anilide anions act as
      MU-bridging ligands and the 1,2-dimeth-oxy-ethane mol-ecules display a MU(2)
      kappa(3)-O,O' coordination mode. As a result of this connectivity, a polymeric
      chain structure parallel to [100] is formed, consisting of Na(2)O(2) and
      Na(2)N(2) four-membered rings. It should be noted that the remaining H atom of
      the anilide NH group is not involved in hydrogen bonding.

PMID- 23125626
TI  - MU(2)-m-Xylylenebis(salicylaldiminato)-bis-(eta(4)-1,5-cyclo-octa
      diene)dirhodium(I) dichloro-methane solvate.
AB  - In the title solvate, [Rh(2)(C(22)H(18)N(2)O(2))(C(8)H(12))(2)].CH(2)Cl(2), each
      organometallic mol-ecule is composed of two Rh(I) cations, the tetra-dentate
      dianion alpha,alpha'-bis-(salicylaldiminato)-m-xylene and two 1,5-cyclo-octa
      diene (COD) ligands. Each Rh(I) atom is coordinated by one O atom [Rh-O = 2.044
      (2) and 2.026 (2) A], one N atom [Rh-N = 2.083 (2) and 2.090 (2) A], and one COD
      ligand via two eta(2)-bonds, each directed toward the mid-point of a C=C bond
      (Cg): Rh-Cg = 2.007 (2), 2.013 (2), 2.000 (2) and 2.021 (2) A. Each Rh(I) atom
      has a quasi-square-planar coordination geometry, with average r.m.s. deviations
      of 0.159 (1) and 0.204 (1) A from the mean planes defined by Rh and the termini
      of its four coordinating bonds. The two COD ligands have quasi-C(2) symmetry,
      twisted from ideal C(2v) symmetry by 30.0 (3) and -33.1 (3) degrees , and are
      quasi-enanti-omers of one another. The intra-molecular Rh?Rh distance of 5.9432
      (3) A suggests that there is no direct metal-metal inter-action.

PMID- 23125627
TI  - N-Ferrocenylmethyl-2-nitro-aniline.
AB  - In the title compound, [Fe(C(5)H(5))(C(12)H(11)N(2)O(2))], the two cyclo-penta
      dienyl (Cp) rings are nearly eclipsed and parallel to each other, the dihedral
      angle between their mean planes being 2.54 (1) degrees . One of the Cp rings is
      substituted by a nitro-benzenamine group, which is essentially perpendicular to
      the substituted cyclo-penta-dienyl ring, with an N-C(H(2))-C-C torsion angle of
      89.8 (2) degrees . Intra-molecular N-H?O and N-H?N hydrogen bonds occur. In the
      crystal, weak C-H?O hydrogen bonds link adjacent mol-ecules.

PMID- 23125628
TI  - N'-[(E)-5-Bromo-2-hy-droxy-3-meth-oxy-benzyl-idene]-4-meth-oxy-benzohydrazide
      monohydrate.
AB  - In the title compound, C(16)H(15)BrN(2)O(4).H(2)O, the hydrazide mol-ecule is
      nearly planar, with a largest deviation from the mean plane through the non-H
      atoms of 0.106 (4) A and a dihedral angle between the benzene rings of 1.98 (16)
      degrees . This mol-ecule adopts an E conformation about the C=N bond and an intra
      molecular O-H?N hydrogen bond increases the rigidity. In the crystal, some mol
      ecules of the title hydrazide are replaced by mol-ecules of its 6-bromo isomer,
      and the Br atom from this admixture mol-ecule was refined to give a partial
      occupancy of 0.0523 (13). The hydrazide and water mol-ecules are linked through
      classical N-H?O and O-H?O hydrogen bonds, forming layers parallel to (110). C
      H?pi inter-actions are also present.

PMID- 23125629
TI  - N-(3,5-Dimethyl-phen-yl)-2-nitro-benzene-sulfonamide.
AB  - The asymmetric unit of the title compound, C(14)H(14)N(2)O(4)S, consists of two
      crystallographically independent mol-ecules. The mol-ecules are twisted at the S
      N bonds with C-S-N-C torsion angles of 44.2 (3) and -49.3 (3) degrees . The
      dihedral angles between the benzene rings in the two mol-ecules are 71.53 (7) and
      72.11 (7) degrees . The amide H atoms exhibit bifurcated intra- and inter
      molecular hydrogen bonds; the intra-molecular N-H?O(N) hydrogen bonds generate
      S(7) motifs. In the crystal, the independent mol-ecules are separately connected
      through the inter-molecular N-H?O(S) hydrogen bonds, generating a C(4) motif and
      a helical chain along the b axis for one mol-ecule and an R(2) (2)(8) motif and
      an inversion dimer for the other. The crystal studied was a pseudo-merohedral
      twin with twin law (-100/0-10/001), the refined ratio of the twin domains being
      0.7876 (12):0.2124 (12).

PMID- 23125630
TI  - 4-Methyl-N-(2-phenyl-eth-yl)-2-propyl-1H-benzimidazole-6-carboxamide.
AB  - There are two independent mol-ecules in the asymmetric unit of the title
      compound, C(20)H(23)N(3)O, in which the dihedral angles between the phenyl ring
      of the phenyl-ethyl-amino group and the benzimidazole system are 73.98 (15) and
      15.93 (16) degrees . The crystal packing features N-H?O and N-H?N hydrogen bonds.

PMID- 23125631
TI  - S-Phenyl benzothio-ate.
AB  - In the title compound, C(13)H(10)OS, the phenyl rings are inclined to one another
      by 51.12 (8) degrees . There is a short C-H?S contact in the molecule.In the
      crystal, molecules are linked via C-H?O hydrogen bonds forming chains along the a
      axis. Molecules are also linked by C-H?pi and weak pi-pi interactions [centroid
      centroid distance = 3.9543 (10) A].

PMID- 23125632
TI  - Quinoline-8-sulfonamide.
AB  - In the title compound, C(9)H(8)N(2)O(2)S, the sulfamoyl NH(2) group is involved
      in intra-molecular N-H?N and inter-molecular N-H?O hydrogen bonding. In the
      crystal, molecules are linked via pairs of N-H?O hydrogen bonds, forming
      inversion dimers, which are further associated through pi-pi stacking inter
      actions between the quinoline benzene rings [centroid-centroid distance = 3.649
      (1) A] into a one-dimensional polymeric structure extending along the a axis.

PMID- 23125633
TI  - 3,3'-(Piperazine-1,4-diium-1,4-di-yl)di-propionate dihydrate.
AB  - During the recrystallization of 3-[4-(2-carb-oxy-eth-yl)piperazin-1-yl]propionic
      acid, the carb-oxy-lic acid H atoms were transferred to the piperazine N atoms,
      forming the title compound, C(10)H(18)N(2)O(4).2H(2)O, in which the zwitterion
      lies about an inversion center. In the crystal, bifurcated N-H?(O,O) hydrogen
      bonds connect the zwitterions into a two-dimensional framework parallel to (-102)
      forming R(4) (4)(30) rings. O-H?O hydrogen bonds involving the solvent water mol
      ecules connect the two-dimensional framework into a three-dimensional network. In
      addition, weak C-H?O hydrogen bonds are observed.

PMID- 23125634
TI  - 4-Dimethyl-amino-N'-(4-nitro-benzyl-idene)benzohydrazide methanol monosolvate.
AB  - In the title compound, C(16)H(16)N(4)O(3).CH(3)OH, the aromatic rings form a
      dihedral angle of 0.4 (2) degrees . The nitro group is twisted from the attached
      benzene ring by 7.5 (2) degrees . In the crystal, N-H?O and O-H?O hydrogen bonds
      link alternating hydrazone and methanol mol-ecules into chains in [100]. The
      crystal packing exhibits pi-pi inter-actions between aromatic rings from
      neighbouring chains [centroid-centroid distances = 3.734 (3) and 3.903 (3) A].

PMID- 23125635
TI  - 2-[(Anilino)(2-nitro-phen-yl)meth-yl]cyclo-hexa-none.
AB  - In the title compound, C(19)H(20)N(2)O(3), the cyclo-hexa-none ring adopts a
      chair conformation with the amino-methyl group is positioned equatorially. An
      intra-molecular N-H?O hydrogen bond occurs. In the crystal, mol-ecules are linked
      by N-H?O hydrogen bonds.

PMID- 23125636
TI  - A triclinic polymorph of 4-cyano-pyridinium hydrogen chloranilate.
AB  - THE ASYMMETRIC UNIT OF THE TRICLINIC POLYMORPH OF THE TITLE COMPOUND (SYSTEMATIC
      NAME: 4-cyano-pyridinium 2,5-dichloro-4-hy-droxy-3,6-dioxocyclo-hexa-1,4-dien-1
      olate), C(6)H(5)N(2) (+).C(6)HCl(2)O(4) (-), consists of two crystallographically
      independent cation-anion units, in each of which the cation and the anion are
      linked by an N-H?O hydrogen bond. In the units, the dihedral angles between the
      cation and anion rings are 78.43 (11) and 80.71 (11) degrees . In the crystal,
      each unit independently forms a chain through N-H?O and O-H?N hydrogen bonds; one
      chain runs along the c axis while the other runs along [011]. Weak C-H?O, C-H?N
      and C-H?Cl inter-actions are observed between the chains.

PMID- 23125637
TI  - N-(2-{[5-Bromo-2-(piperidin-1-yl)pyrimidin-4-yl]sulfan-yl}-4-meth-oxy-phen-yl)-4
      methyl-benzene-sulfonamide.
AB  - In the title compound, C(23)H(25)BrN(4)O(3)S(2), the benzene rings bridged by the
      sulfonamide group are tilted relative to each other by 69.7 (1) degrees  and the
      dihedral angle between the sulfur-bridged pyrimidine and benzene rings is 70.4
      (1) degrees . The mol-ecular conformation is stabilized by a weak intra-molecular
      pi-pi stacking inter-action between the pyrimidine and the 4-methyl benzene rings
      [centroid-centroid distance = 3.633 (2) A]. The piperidine ring adopts a chair
      conformation. In the crystal, mol-ecules are linked into inversion dimers by
      pairs of N-H?O hydrogen bonds.

PMID- 23125638
TI  - 2,2,2-Trichloro-N-(3-nitro-phen-yl)acetamide.
AB  - In the title compound, C(8)H(5)Cl(3)N(2)O(3), the dihedral angle between the
      nitro-phenyl ring and the acetamide group is 5.47 (6) degrees . In the crystal, N
      H?O and C-H?O hydrogen bonds link the mol-ecules into chains running parallel to
      the b axis.

PMID- 23125639
TI  - A new polymorph of 2-(2H-benzotriazol-2-yl)acetic acid.
AB  - A new polymorph of 2-(benzotriazol-2-yl)acetic acid, C(8)H(7)N(3)O(2),
      crystallizes in the space group C2/c (Z = 8). The non-planar mol-ecule has a
      synplanar conformation of the carb-oxy group. The crystal structure features
      helices parallel to the b axis sustained by O-H?N hydrogen bonding which are
      similar to those in the known polymorph [Giordano & Zagari (1978 ?). J. Chem.
      Soc. Perkin Trans. 2, pp. 312-315]. However, in the title structure, columns are
      formed by pi-pi stacking inter-actions between benzotriazole fragments of
      centrosymmetrically related adjacent mol-ecules [centroid-centroid distances =
      3.593 (10) and 3.381 (10) A] whereas pi-pi stacking inter-actions are not
      observed in the other polymorph. In the crystal of the title compound, C-H?O
      inter-actions are also observed.

PMID- 23125640
TI  - Ethyl N-[2-(4-phen-oxy-phen-oxy)eth-yl]carbamate.
AB  - The title compound, C(17)H(19)NO(4), which is a non-toxic insect growth regulator
      with the common name fenoxycarb, contains two independent and conformationally
      different mol-ecules in the asymmetric unit. Although the inter-ring dihedral
      angles are similar [62.21 (15) and 63.00 (14) degrees ], the side-chain
      orientations differ. In the crystal, the mol-ecules are linked through N-H?O
      hydrogen-bonding associations, giving chains which extend along [110], while
      intra- and inter-molecular aromatic C-H?pi inter-actions give sheet structures
      parallel to [110].

PMID- 23125641
TI  - 5-Cyclo-hexyl-2-(4-methyl-phen-yl)-3-methyl-sulfinyl-1-benzofuran.
AB  - In the title compound, C(22)H(24)O(2)S, the cyclo-hexyl ring adopts a chair
      conformation. In the crystal, mol-ecules are linked by weak C-H?O and C-H?pi
      inter-actions. In the methyl-sulfinyl group, the methyl group and S atom are
      disordered over two sets of sites, with site-occupancy factors of 0.58 (3) and
      0.42 (3). In the ring of the 4-methyl-phenyl group, the four C atoms are
      disordered over two sets of sites, with site-occupancy factors of 0.858 (5) and
      0.142 (5).

PMID- 23125642
TI  - Dimethyl 7-meth-oxy-tetra-cyclo-[6.4.0.0(2,4).0(3,7)]dodeca-1(12),5,8,10-tetra
      ene-3,4-dicarboxyl-ate.
AB  - The title compound, C(17)H(16)O(5), is a previously unreported substituted
      semibulvalene cage compound (that is, a tricyclic hydro-carbon formed from one
      cyclo-propane and two cyclo-pentene rings which also has one double bond fused to
      a benzene ring). It has one meth-oxy substituent attached to the bridgehead C
      atom that links only the two cyclo-pentene rings and two methyl carboxyl-ate
      groups located on the C atom shared by all three non-benzene rings and that
      shared only between the cyclo-propane and the cyclo-pentene rings. The
      stereochemistry of the two enanti-omers (racemate) that assemble in each unit
      cell is RRRS and SSSR. In the crystal, mol-ecules are linked via C-H?O hydrogen
      bonds and C-H?pi inter-actions, forming double-layered sheets lying perpendicular
      to the a axis.

PMID- 23125643
TI  - 5-Ethyl-3-(2-fluoro-phenyl-sulfon-yl)-2-methyl-1-benzofuran.
AB  - In the title compound, C(17)H(15)FO(3)S, the 2-fluoro-phenyl ring makes a
      dihedral angle of 89.12 (8) degrees  with the mean plane of the benzofuran
      fragment. In the crystal, mol-ecules are linked by weak C-H?O and C-H?pi inter
      actions.

PMID- 23125644
TI  - 5-(4-Fluoro-benzyl-idene)-4'-(4-fluoro-phen-yl)-1,1'-dimethyl-dispiro-[piperidine
      3,3'-pyrrolidine-2',3''-indoline]-4,2''-dione.
AB  - The asymmetric unit of the title compound, C(30)H(27)F(2)N(3)O(2), contains two
      independent mol-ecules. The pyrrolidine five-membered ring assumes an envelope
      conformation (with the CH(2) atom at the flap) in one mol-ecule and a twisted
      conformation in the other one. In both independent mol-ecules, the 4-piperidinone
      rings adopt a similar twisted chair conformation. In the crystal, the two
      independent mol-ecules form an R(2) (2)(8) dimer through a pair of N-H?O hydrogen
      bonds; the R(2) (2)(8) dimers are connected via weak C-H?O hydrogen bonds,
      leading to a chain extending along the c axis.

PMID- 23125645
TI  - 2,4-Bis(4-eth-oxy-phen-yl)-3-aza-bicyclo-[3.3.1]nonan-9-one.
AB  - The title compound, C(24)H(29)NO(3), exists in a twin-chair conformation with an
      equatorial orientation of the 4-eth-oxy-phenyl groups. The benzene rings are
      inclined to each other at an angle of 28.0 (1) degrees . In the crystal, weak C
      H?O inter-actions link mol-ecules related by translation into chains along the b
      axis. The crystal packing exhibits pi-pi inter-actions between the benzene rings
      of neighbouring mol-ecules [centroid-centroid distance = 3.692 (3) A].

PMID- 23125646
TI  - (2E)-N-Methyl-2-[(2E)-3-phenyl-prop-2-en-1-yl-idene]hydrazinecarbothio-amide.
AB  - The title compound, C(11)H(13)N(3)S, is close to being planar, with a dihedral
      angle of 9.64 (3) degrees  between the benzene ring and the thio-semicarbazone
      mean plane, maintained by the presence of pi-conjugation in the chain linking the
      the two systems. In the crystal, N-H?S hydrogen bonds form centrosymmetric dimers
      through a cyclic association [graph-set R(2) (2)(8)].

PMID- 23125647
TI  - 2,6-Dimeth-oxy-9,10-anthraquinone.
AB  - The title compound, C(16)H(12)O(4), crystallizes with two half-mol-ecules in the
      asymmetric unit, each of which is completed by a crystallographic inversion
      center. The two crystallographically independent mol-ecules have almost the same
      geometry and are almost planar [maximum deviations = 0.018 (3) and 0.049 (3) A].
      They adopt a conformation in which the C(meth-yl)-O bonds are directed along the
      mol-ecular short axis [C-C-O-C torsion angles of 179.6 (2) and 178.0 (2) degrees
      ]. In the crystal, the mol-ecular packing is characterized by a combination of a
      columnar stacking and a herringbone-like arrangement. The mol-ecules form slipped
      pi-stacks along the b axis, in which there are two kinds of columns differing
      from each other in their slippage. The inter-planar distances between neighboring
      mol-ecules are 3.493 (3) for one column and 3.451 (2) A for the other.

PMID- 23125648
TI  - (3,4-Dimeth-oxy-phen-yl)[2-(thio-phen-2-ylcarbon-yl)phen-yl]methanone.
AB  - In the title compound, C(20)H(16)O(4)S, the thiophene ring makes dihedral angles
      of 72.9 (2) and 60.5 (2) degrees , respectively, with the dimethoxy benzene and
      phenyl rings. In the crystal, C-H?O hydrogen bonds link the mol-ecules into a
      C(9) chain along the b axis. The S and C atoms of the thio-phene ring are
      disordered over two sets of sites [site occupancies = 0.675 (3) and 0.325 (3)]. A
      short inter-molecular S?O contact [3.084 (2) A] is observed in the crystal
      structure, which also features C-H?pi inter-actions.

PMID- 23125649
TI  - 1-(2,4-Dinitro-phen-yl)-3-phenyl-4-phenyl-sulfanyl-1H-pyrazole.
AB  - In the title mol-ecule, C(21)H(14)N(4)O(4)S, the pyrazole ring forms dihedral
      angles of 45.6 (1), 87.7 (1) and 27.4 (1) degrees  with the phenyl, sulfur
      substituted benzene and nitro-substituted benzene rings, respectively. In the
      crystal, mol-ecules are connected by weak C-H?O and C-H?N hydrogen bonds into
      layers parallel to (010).

PMID- 23125650
TI  - (E)-4-Meth-oxy-N'-(3,4,5-trihy-droxy-benzyl-idene)benzohydrazide methanol
      monosolvate.
AB  - The title compound, C(15)H(14)N(2)O(5).CH(3)OH, displays an E conformation about
      the azomethine double bond [C=N = 1.277 (2) A] and the benzene rings are inclined
      to one another by 18.28 (9) degrees . An intra-molecular O-H?O hydrogen bond
      occurs between the para-OH group and one of the meta-O atoms of the 3,4,5-trihy
      droxy-benzyl-idene group. In the crystal, the components are linked into a three
      dimensional network by O-H?O, O-H?N and C-H?O hydrogen bonds.

PMID- 23125651
TI  - (Z)-1,4-Diphenyl-but-1-en-3-ynyl acetate.
AB  - The title compound, C(18)H(14)O(2), is almost planar with a dihedral angle of
      1.24 (2) degrees  between the phenyl-ethynyl and styryl groups. The acet-oxy
      group is tilted by 82.46 (2) and 82.26 (3) degrees  with respect to the benzene
      ring planes.

PMID- 23125652
TI  - meso-(1S*,21R*)-25-Methyl-8,11,14-trioxa-22,24,25-triaza-tetra-cyclo
      [19.3.1.0(2,7).0(15,20)]penta-cosa-2,4,6,15(20),16,18-hexa-ene-23-thione chloro
      form monosolvate.
AB  - The title compound crystallizes as a chloro-form solvate,
      C(20)H(23)N(3)O(3)S.CHCl(3), with two crystallographically independent units. The
      independent units have distinctly different inter-action patterns between the aza
      crown macrocycle and the chloro-form solvent mol-ecule. In one of them, the
      chloro-form mol-ecule forms C-H?N and Cl?H-C hydrogen bonds with the aza-crown
      macrocycle (as a proton donor and an acceptor, respectively), whereas in the
      other, one of the chloro-form mol-ecules is bound to the aza-crown macrocycle by
      an attractive Cl?O [3.080 (3) A] inter-action. The aza-crown macrocycles of
      different units are structurally similar; the aza-14-crown-3-ether ring adopts a
      bowl conformation with dihedral angles between the planes of the fused benzene
      rings of 60.7 (1) and 68.0 (1) degrees . The triazinane-thione ring in both cases
      has a sofa conformation. The crystal packing is characterized by N-H?S, N-H?O, C
      H?Cl and C-H?S hydrogen bonds.

PMID- 23125653
TI  - (4-Meth-oxy-phen-yl)(4-methyl-cyclo-hex-yl)methanone.
AB  - The title compound, C(15)H(20)O(2), crystallizes with two independent mol-ecules
      of similar geometry in the asymmetric unit. The cyclo-hexyl ring adopts a chair
      conformation in each mol-ecule. In the crystal, mol-ecules related by translation
      are linked into chains along the a axis via weak C-H?O inter-actions.

PMID- 23125654
TI  - 6-Bromo-4-[2-(4-fluoro-benzyl-idene)hydrazin-1-yl-idene]-1-methyl-3,4-dihydro-1H
      2lambda(6),1-benzothia-zine-2,2-dione.
AB  - In the title compound, C(16)H(13)BrFN(3)O(2)S, the dihedral angle between the
      aromatic rings is 2.55 (19) degrees  and the C=N-N=C torsion angle is 178.9 (3)
      degrees . The conformation of the thia-zine ring is an envelope, with the S atom
      displaced by -0.811 (3) A from the mean plane of the other five atoms (r.m.s.
      deviation = 0.042 A). In the crystal, C-H?O inter-actions link the mol-ecules and
      weak aromatic pi-pi stacking between the fluoro-benzene and bromo-benzene rings
      [centroid-centroid separation = 3.720 (2) A and inter-planar angle = 2.6 (2)
      degrees ] is also observed.

PMID- 23125655
TI  - 2,2'-{[(2,2'-Dieth-oxy-1,1'-binaphthalene-6,6'-di-yl)bis-(4,1-phenyl-ene)]bis
      (methan-ylyl-idene)}dimalononitrile.
AB  - The title compound, C(44)H(30)N(4)O(2), was prepared from 6,6'-dibromo-2,2'-dieth
      oxy-1,1'-binaphthalene through a coupling reaction with 4-(4,4,5,5-tetra-methyl
      1,3,2-dioxaborolan-2-yl)benzaldehyde followed by a Knoevenagel reaction with
      malononitrile. The dihedral angle between the symmetry-related naphthalene ring
      systems is 68.82 (8) degrees  while the dihedral angle between the the
      naphthalene ring system and the adjacent benzene ring is 16.92 (7) degrees . Four
      symmetry-independent mol-ecules which are linked by inter-molecular C-H?pi inter
      action generate the packing motif in the crystal structure. One of the CN groups
      is disordered over two sets of sites in a 0.60 (2):0.40 (2) ratio.

PMID- 23125656
TI  - Benzyl 2-benzyl-4-[(3aS,7aR)-2,3,3a,4,5,6,7,7a-octa-hydro-1H-isoindol-2-yl]-4
      oxobutano-ate.
AB  - In the title compound, C(26)H(31)NO(3), the octa-hydro-1H-isoindole ring is not
      planar and the two rings are twisted with a C-C-C-C torsion angle of 73.6 (4)
      degrees . The six-membered ring has a chair conformation while the five-membered
      ring has an envelope conformation on the C-atom in position 7a. The H atoms in
      the 3a- and 7a-psitions are cis and the H-C-C-H torsion angle is 42.36 degrees .

PMID- 23125657
TI  - 9-Meth-oxy-9-(2-meth-oxy-phen-yl)-9H-xanthene.
AB  - In the title compound, C(21)H(18)O(3), the xanthene system and the meth-oxy
      phenyl ring are practically orthogonal with a dihedral angle between their mean
      planes of 89.27 (3) degrees . The meth-oxy group attached to the phenyl ring
      makes a C-O-C-C torsion angle of 11.56 (18) degrees . In the crystal, mol-ecules
      are linked by C-H?O inter-actions into chains along [010]. Weak C-H?pi inter
      actions also occur.

PMID- 23125658
TI  - (2Z,2'Z)-Diethyl 3,3'-[butane-1,4-diylbis(aza-nedi-yl)]bis-(but-2-enoate).
AB  - The whole mol-ecule of the title beta-enamino-ester, C(16)H(28)N(2)O(4), is
      generated by a crystallographic inversion center, situated at the mid-point of
      the central C-C bond of the 1,4-diamino-butane segment. There are two intra
      molecular N-H?O hydrogen bonds that generate S(6) ring motifs. This leads to the
      Z conformation about the C=C bonds [1.3756 (17) A]. The mol-ecule is S-shaped
      with the planar central 1,4-diamino-butane segment [maximum deviation for non H
      atoms = 0.0058 (13) A] being inclined to the ethyl butyl-enonate fragment [C-C-O
      C-C=C-C; maximum deviation = 0.0710 (12) A] by 15.56 (10) degrees . In the
      crystal, mol-ecules are linked via C-H?O inter-actions, leading to the formation
      of an undulating two-dimensional network lying parallel to the bc plane.

PMID- 23125659
TI  - 3-Methyl-amino-3-phenyl-propan-1-ol.
AB  - The title compound, C(10)H(15)NO, is an amino alcohol with the hy-droxy group
      residing on the terminal C atom. Apart from the hy-droxy group and the phenyl
      ring, all non-H atoms are almost coplanar. In the crystal, classical O-H?N and N
      H?O hydrogen bonds connect the mol-ecules into centrosymmetric dimers [R(2)
      (2)(12) descriptor] and tetra-meric units [R(4) (4)(8) descriptor] as ring
      motifs, consolidating a three-dimensional network.

PMID- 23125660
TI  - 3-(9H-Fluoren-9-yl)-1,3-diphenyl-propan-1-one.
AB  - In the title compound, C(28)H(22)O, the fluorene ring system is approximately
      planar [maximum deviation = 0.044 (2) A] and forms dihedral angles of 69.88 (6)
      and 89.46 (6) degrees  with the phenyl rings. The crystal packing is stabilized
      by weak pi-pi stacking inter-actions, with centroid-centroid distances of 3.7172
      (13) and 3.7827 (11) A.

PMID- 23125662
TI  - Intra- and inter-molecular proton transfer in 2,6-diamino-pyridinium 4-hy-droxy
      pyridin-1-ium-2,6-dicarboxyl-ate.
AB  - Chelidamic acid (4-hy-droxy-pyridine-2,6-dicarb-oxy-lic acid) and 2,6-diamino
      pyridine react to form the title salt, C(5)H(8)N(3) (+).C(7)H(4)NO(5) (-); there
      are two formula units in the asymmetric unit. The pyridine N atom of 2,6-diamino
      pyridine is protonated whereas chelidamic acid is deprotonated at both carboxyl
      ate groups but protonated at the N atom; the reaction involves intra- and inter
      molecular proton transfer. In the crystal, each 2,6-diamino-pyridinium cation
      participates in five strong N-H?O hydrogen bonds (including one bifurcated
      hydrogen bond). The crystal structure also features strong O-H?O hydrogen bonds
      between the chelidamate anions, leading to chains along the a axis.

PMID- 23125663
TI  - 1-Butyl-3-ethyl-1H-benzimidazol-3-ium tetra-fluoro-borate.
AB  - In the title salt, C(13)H(19)N(2) (+).BF(4) (-), an ionic liquid, the butyl and
      ethyl substituents bonded to the N atoms of the imidazole ring [r.m.s. deviation
      = 0.019 (1) A] adopt equatorial positions. The crystal structure exhibits slipped
      pi-pi inter-actions between the imidazole and benzene rings of neighbouring mol
      ecules [centroid-centroid distance = 3.529 (2) A]. In the tetra-fluoro-borate
      anion, the B and F atoms are disordered over two sets of sites with site
      occupancy factors of 0.813 (7) and 0.187 (7).

PMID- 23125664
TI  - 1-(3-Benzyl-4,6-dibenz-yloxy-2-hy-droxy-phen-yl)ethanone.
AB  - The title compound, C(29)H(26)O(4), is essentially planar in the acetophenone
      portion that includes both the hy-droxy and a benz-yloxy O atoms, with an r.m.s.
      deviation of 0.0311 A. The other two substituents inter-sect the plane at 70.45
      (3) and 59.55 (4) degrees . In the molecule there is an intramolecular O-H?O
      hydrogen bond. In the crystal, mol-ecules are linked by C-H?O hydrogen bonds, as
      well as C-H?pi and pi-stacking inter-actions, with centroid-centroid distances
      3.6570 (2) A.

PMID- 23125661
TI  - 2-(3,5-Dimethyl-1,1-dioxo-2H-1lambda(6),2,6-thia-diazin-4-yl)benzoic acid.
AB  - In the title mol-ecule, C(12)H(12)N(2)O(4)S, the S atom of the thia-diazine ring
      deviates by 0.5104 (4) A from the mean plane of the other five atoms [largest
      deviation = 0.0623 (15) A] giving a slightly distorted sofa conformation. The
      carb-oxy H atom was refined as disordered over two sets of sites with refined
      occupancies of 0.58 (2) and 0.48 (2). This corresponds to rotational disorder of
      the C=O and O-H groups about the attached C-C bond. In the crystal, O-H?O and N
      H?O hydrogen bonds connect the mol-ecules into chains along [110].

PMID- 23125665
TI  - 2-Carbamoyl-3,4,5,6-tetra-fluoro-benzoic acid.
AB  - In the title compound, C(8)H(3)F(4)NO(3), the carb-oxy group lies nearly in the
      plane of the ring with a C-C-C-O torsion angle of -10.5 (4) degrees . The
      carbamoyl group is almost perpendic-ular to the benzene ring [C-C-C-O torsion
      angle = 82.2 (4)  degrees ]. In the crystal, molecules are linked via O-H?O and N
      H?O hydrogen bonds involving the carbamoyl and carb-oxy groups.

PMID- 23125666
TI  - N-(2-Carb-oxy-eth-yl)-2,5-dide-oxy-2,5-imino-d-mannonic acid [(3R,4R,5R)-1-(2
      carb-oxy-eth-yl)-3,4-dihy-droxy-5-hy-droxy-methyl-l-proline].
AB  - The absolute stereochemistry of the title compound, C(9)H(15)NO(7), was
      determined from the use of d-glucuronolactone as the starting material. The
      compound crystallizes as the zwitterion. The five-membered ring adopts an
      envelope conformation with the -CH(2)OH-substituted C atom forming the flap. An
      intramolecular N-H?O hydrogen-bond occurs. In the crystal, the compound exists as
      a three-dimensional O-H?O intermolecular hydrogen-bonded network with each mol
      ecule acting as a donor and acceptor for four hydrogen bonds.

PMID- 23125667
TI  - 2-Amino-5-nitro-N-[(E)-thio-phen-2-yl-methyl-idene]aniline.
AB  - In the title mol-ecule, C(11)H(9)N(3)O(2)S, the thio-phene and benzene rings form
      a dihedral angle of 17.68 (9) degrees . The thio-phene S atom and the imine N
      atom are syn with respect to each other. In the crystal, N-H?O and N-H?N hydrogen
      bonds connect mol-ecules, forming a two-dimensional network parallel to (10-1).

PMID- 23125669
TI  - (Z)-N-(1-Eth-oxy-ethyl-idene)-2,6-bis-(propan-2-yl)anilinium chloride
      hemihydrate.
AB  - In the title compound, C(16)H(26)NO(+).Cl(-).0.5H(2)O, the asymmetric unit
      consists of two independent cations, their respective chloride anions and a
      solvent water mol-ecule. Together they form a discrete crescent-shaped entity
      linked by hydrogen bonds from the central water atom to two Cl(-) ions and from
      the latter to two protonated imine groups. The geometries of the two independent
      cations are essentially the same. The planar N=C(O)CH(3) groups in each (r.m.s.
      deviations = 0.0011 and 0.0026 A) form dihedral angles of 75.28 (5) and 79.10 (4)
      degrees  with the benzene rings. In one cation, the methyl atoms of one of the
      isopropyl groups were modeled as disordered over two sets of sites, with refined
      occupancies of 0.589 (17) and 0.411 (17).

PMID- 23125668
TI  - (Z)-N-Ethyl-2-(5-fluoro-2-oxoindolin-3-yl-idene)hydrazinecarbothio-amide.
AB  - In the title compound, C(11)H(11)FN(4)OS, an intra-molecular N-H?O hydrogen bond
      generates an S(6) ring. In the crystal, mol-ecules form chains through N-H?O
      hydrogen bonds, which are extended by N-H?S hydrogen bonds into an infinite three
      dimensional network.

PMID- 23125670
TI  - Tautomerism in 10-(hy-droxy-imino)-phenanthren-9-one.
AB  - In the title compound, C(14)H(9)NO(2), a static disorder exists between the keto
      oxime and hy-droxy-nitroso tautomers, in an approximate ratio of 4.6:1, based on
      refined occupancies for disordered parts. No inter-molecular hydrogen bonding is
      present in the crystal structure. Instead, both tautomers exhibit similar intra
      molecular O-H?O hydrogen bonds.

PMID- 23125671
TI  - 4-Nitro-N-phenyl-benzene-sulfonamide.
AB  - In the title compound, C(12)H(10)N(2)O(4)S, the dihedral angle between the
      aromatic rings is 36.19 (18) degrees . In the crystal, N-H?O hydrogen bonds link
      the mol-ecules into C(4) chains running along the a axis.

PMID- 23125672
TI  - 2,6-Dibromo-4-formyl-phenyl 3-phenyl-prop-2-enoate.
AB  - Mol-ecules of the title compound, C(16)H(10)Br(2)O(3), adopt an E conformation
      about the C=C double bond. The dihedral angle between the two aromatic rings is
      78.0 (7) degrees . In the crystal, mol-ecules are linked through weak C-H?O
      hydrogen bonds.

PMID- 23125673
TI  - Ethyl 2-benzene-sulfonamido-4-methyl-penta-noate.
AB  - In the title compound, C(14)H(21)NO(4)S, the O-S-O angle is 120.06 (11) degrees ,
      with the S atom adopting a distorted tetra-hedral geometry. In the crystal, N-H?O
      hydrogen bonds connect the mol-ecules along the a axis, generating an infinite
      chain. The disordered C atoms of the isobutyl group were refined with the C-C
      distances restrained to 1.52 (1) A and the occupancy ratio refined to 0.504
      (3):0.496 (3).

PMID- 23125674
TI  - 2,2'-[(3-Bromo-4-hy-droxy-5-meth-oxy-phen-yl)methyl-idene]bis-(3-hy-droxy-5,5
      dimethyl-cyclo-hex-2-en-1-one).
AB  - In the title compound, C(24)H(29)BrO(6), the dihedral angle between the cyclo
      hexenone mean planes is 57.63 (2) degrees  while the dihedral angles between the
      benzene ring and the cyclo-hexenone mean planes are 58.42 (2) and 69.08 (3)
      degrees . The two cyclo-hexenone rings both show an envelope conformation, with
      the C atom bearing two methyl groups as the flap atom in each ring. Two intra
      molecular O-H?O hydrogen bonds occur. In the crystal, molecules are linked via
      pairs of O-H?O hydrogen bonds, forming inversion dimers.

PMID- 23125675
TI  - 2-(5-Chloro-1,3-benzothia-zol-2-yl)-4-meth-oxy-phenol.
AB  - In the mol-ecule of the title compound, C(14)H(10)ClNO(2)S, the dihedral angle
      between the almost planar benzothia-zole ring system [maximum deviation = 0.005
      (2) A] and the benzene ring is 1.23 (9) degrees . The conformation of the mol
      ecule is stabilized by an intra-molecular O-H?N hydrogen bond, forming an S(6)
      ring motif. In the crystal, mol-ecules are linked into layers parallel to the ac
      plane by C-H?O hydrogen bonds and pi-pi stacking inter-actions [centroid-centroid
      distance = 3.7365 (12) A].

PMID- 23125677
TI  - 1-(Piperidin-1-yl)-9,10-anthraquinone.
AB  - In the title compound, C(19)H(17)NO(2), the piperidine ring adopts a chair
      conformation. The mean planes of the piperidine ring and the anthracene ring
      system are inclined at a dihedral angle of 38.7 (1) degrees . In the crystal,
      adjacent mol-ecules are linked through C-H?pi and pi-pi [centroid-centroid
      distance = 3.782 (1) A] inter-actions, forming a layer parallel to the bc plane.

PMID- 23125676
TI  - Ethyl 3-eth-oxy-carbonyl-methyl-7-methyl-5-phenyl-5H-thia-zolo[3,2-a]pyrimidine-6
      carboxyl-ate.
AB  - In the title compound, C(20)H(22)N(2)O(4)S, the central pyrimidine ring
      incorporating a chiral C atom is significantly puckered and adopts a slight boat
      conformation with C atom bearing the phenyl ring and the N atom opposite
      displaced by 0.367 (2) and 0.107 (2) A, respectively, from the plane formed by
      the remaining ring atoms. The benzene ring is positioned axially to the
      pyrimidine ring, making a dihedral angle of 88.99 (5) degrees . The thia-zole
      ring is essentially planar (r.m.s. deviation = 0.0033 A). In the crystal, pairs
      of C-H?O inter-actions result in centrosymmetric dimers with graph-set motifs
      R(1) (2)(7) and R(2) (2)(8). A weak C-H?pi contact is also observed.

PMID- 23125678
TI  - 2-(4-Fluoro-phen-yl)-1-(4-methyl-phen-yl)-1H-phenanthro[9,10-d]imidazole.
AB  - The phenanthrene tricyclic ring system in the title mol-ecule, C(28)H(19)FN(2),
      is slightly skewed with a dihedral angle of 7.50 (6) degrees  between the outer
      benzene rings. The p-tolyl and fluoro-benzene rings are twisted from the attached
      imidazole ring by 70.40 (7) and 28.33 (7) degrees , respectively. In the crystal,
      C-H?F hydrogen bonds link the mol-ecules into zigzag chains in [001], and weak C
      H?pi inter-actions further consolidate the crystal packing.

PMID- 23125679
TI  - (1S,8R,15S,19R)-17-Benzyl-17-aza-penta-cyclo-[6.6.5.0(2,7).0(9,14).0(15,19)]nona
      deca-2(7),3,5,9(14),10,12-hexa-ene chloro-form monosolvate.
AB  - In the title compound, C(25)H(23)N.CHCl(3), the dihydro-anthracene unit is bent
      with a dihedral angle between the benzene rings of 57.82 (8) degrees . The N atom
      of the pyrrolidine heterocycle, which has an envelope conformation with the N
      atom as the flap, exhibits a pronounced pyramidalization [Sigma(C-N-C) = 328.07
      degrees ], indicating an accentuated N-donor character. In the crystal, this
      behaviour is evident by the C-H?N hydrogen bond involving a solvent mol-ecule and
      the N atom. The absolute configuration at the C-atom fused positions of the
      pyrrolidine group were crystallographically confirmed to be S and R.

PMID- 23125680
TI  - 1-(Naphthalen-1-yl)-3-[(thio-phen-2-yl)carbon-yl]thio-urea.
AB  - In the title compound, C(16)H(12)N(2)OS(2), the dihedral angles between the mean
      planes of the central thio-urea core and the thio-phene ring and the naphthalene
      ring system are 1.8 (2) and 6.45 (18) degrees , respectively. The mol-ecule
      adopts a trans-cis conformation with respect to the position of thio-phenoyl and
      naphthyl groups relative to the S atom across the thiourea C-N bonds. Both the
      thio-phene ring and the sulfanyl-idene S atom are disordered over two sets of
      sites with occupancies of 0.862 (3):0.138 (3) and 0.977 (3):0.023 (3),
      respectively. An intra-molecular N-H?O hydrogen bond is observed. The crystal
      packing features two N-H?S hydrogen bonds.

PMID- 23125681
TI  - 4-Cyano-anilinium bromide.
AB  - In the crystal structure of the title compound, C(7)H(7)N(2) (+).Br(-), the
      cations are associated into inversion dimers through weak pairwise C-H?N hydrogen
      bonds. The dimers further form stepped sheets via weak pairwise C-H?N hydrogen
      bonds. In the sheets, the spacing between the mean planes of the laterally
      displaced aromatic rings in adjacent dimers is 1.124 (6) A. Three N-H?Br inter
      actions and two weak C-H?Br inter-actions per cation tie the sheets together.

PMID- 23125682
TI  - 3-Amino-1H-1,2,4-triazole-5(4H)-thione-4,4'-bipyridine (1/1).
AB  - The title two-component mol-ecular crystal, C(10)H(8)N(2).C(2)H(4)N(4)S, was
      obtained unexpectedly by reaction of Zn(NO(3))(2).6H(2)O, NH(4)BF(4) with 3-amino
      1,2,4-triazole-5-thione (3-AMT) and 4,4'-bipyridine in water. The dihedral angle
      between the pyridine rings in the 4,4'-bipyridine molecule is 17.00 (13) degrees
      . In the crystal, N-H?N and N-H?S hydrogen bonds between the components lead to
      the formation of a three-dimensional network. Furthermore, the structure features
      face-to-face pi-pi stacking inter-actions between the 4,4'-bipyridine and
      triazole rings, with a centroid-centroid distance of 2.976 (2) A.

PMID- 23125683
TI  - 4-[(2E)-2-(2-Hy-droxy-benzyl-idene)hydrazin-1-yl]benzonitrile.
AB  - The asymmetric unit of the title Schiff base, C(14)H(11)N(3)O, contains two
      independent mol-ecules which have similar conformations. The dihedral angles
      between the benzene rings are 4.19 (9) and 14.18 (9) degrees  in the two mol
      ecules. An intra-molecular O-H?N hydrogen bond stabilizes the mol-ecular
      conformation of each mol-ecules. The crystal packing is dominated by pairs of
      equivalent N-H?N and C-H?O hydrogen bonds which arrange the mol-ecules into
      layers parallel to (-111).

PMID- 23125684
TI  - N-[1-(1H-Pyrrol-2-yl)ethyl-idene]aniline.
AB  - There are two independent mol-ecules in the asymmetric unit of the title
      compound, C(12)H(12)N(2), in which the pyrrole and benzene rings form dihedral
      angles of 72.37 (7) and 82.34 (8) degrees . The imino N-C bond lengths in the two
      mol-ecules are equal [1.286 (2) A] and indicate C=N character. In the crystal,
      each mol-ecule forms a dimer with an inversion-related mol-ecule through a pair
      of classical N-H?N hydrogen bonds.

PMID- 23125685
TI  - 2,4,6-Trimethyl-N-[1-(1H-pyrrol-2-yl)ethyl-idene]aniline.
AB  - There are two independent mol-ecules in the asymmetric unit of the title
      compound, C(15)H(18)N(2), each of which features a syn disposition of the N
      atoms. In each mol-ecule, the pyrrole and benzene rings are essentially
      perpendicular, with dihedral angles of 78.90 (9) and 79.96 (9) degrees . In the
      crystal, the independent mol-ecules are connected by a pair of pyrrole-imino N
      H?N hydrogen bonds, forming a two-mol-ecule aggregate.

PMID- 23125686
TI  - 2-[4-(1H-1,2,4-Triazol-1-yl)phen-yl]-1H-benzimidazole.
AB  - In the title compound, C(15)H(11)N(5), the benzimidazole ring system is nearly
      planar [maximum deviation = 0.039 (2) A], and is oriented at a dihedral angle of
      28.85 (10) degrees  with respect to the benzene ring; the dihedral angle between
      the triazole and benzene rings is 17.30 (15) degrees . In the crystal N-H?N
      hydrogen bonds link the mol-ecules into chains. Weak C-H?N inter-actions are also
      present.

PMID- 23125687
TI  - O,O'-Dimethyl (cyclo-hexyl-amido)-thio-phosphate.
AB  - The P atom in the title compound, C(8)H(18)NO(2)PS, is bonded in a distorted
      tetra-hedral PSO(2)N environment with bond angles in the range of 99.23 (5)
      115.17 (4) degrees . The cyclo-hexane ring is disordered over two sets of sites
      with refined occupancies of 0.528 (5) and 0.472 (5). The ring in both disorder
      components adopts a chair conformation with the N-H group oriented equatorially.
      In the crystal, pairs of P=S?H-N hydrogen bonds form inversion dimers.

PMID- 23125688
TI  - 2-(4-Methyl-phen-yl)quinoline-4-carb-oxy-lic acid.
AB  - In the title compound, C(17)H(13)NO(2), the dihedral angle between the plane of
      the carb-oxy group and the quinoline mean plane is 45.05 (13) degrees , and that
      between the toluene ring mean plane and the quinoline mean plane is 25.29 (7)
      degrees . In the crystal, molecules are linked via O-H?.N hydrogen bonds, forming
      chains propagating along the b-axis direction. These chain are linked via C-H?O
      interactions, forming two-dimensional networks lying parallel to the ab plane.

PMID- 23125689
TI  - 5-Iodo-2,7-dimethyl-3-(4-methyl-phenyl-sulfon-yl)-1-benzofuran.
AB  - In the title compound, C(17)H(15)IO(3)S, the 4-methyl-phenyl ring makes a
      dihedral angle of 76.95 (5) degrees  with the mean plane [r.m.s. deviation =
      0.019 (2) A] of the benzofuran fragment. In the crystal, mol-ecules are linked
      via pairs of C-H?O hydrogen bonds, forming inversion dimers. These dimers are
      connected by slipped pi-pi inter-actions between the benzene rings of
      neighbouring mol-ecules [centroid-centroid distance = 3.671 (3) A and slippage =
      1.049 (3) A].

PMID- 23125690
TI  - 3-(3-Fluoro-phenyl-sulfin-yl)-5-iodo-2,7-dimethyl-1-benzofuran.
AB  - In the title compound, C(16)H(12)FIO(2)S, the 3-fluoro-phenyl ring makes a
      dihedral angle of 76.47 (6) degrees  with the mean plane [r.m.s. deviation =
      0.013 (2) A] of the benzofuran fragment. In the crystal, mol-ecules are linked by
      weak C-H?O hydrogen bonds,forming chains along the b-axis direction, and an I?O
      contact [3.204 (2) A]. The crystal structure also exhibits slipped pi-pi inter
      actions between the 3-fluoro-phenyl rings of neighbouring mol-ecules [centroid
      centroid distance = 3.683 (3) A and slippage = 1.708 (3) A].

PMID- 23125691
TI  - 5-Anilino-3-benzyl-sulfanyl-6-(3-chloro-anilino)-1-phenyl-1H-pyrazolo-[3,4
      d]pyrimidin-4(5H)-one.
AB  - In the title compound, C(30)H(23)ClN(6)OS, the benzyl, the 3-chloro-anilino, the
      phenyl and the anilino groups form dihedral angles of 85.95 (6), 29.63 (7), 28.55
      (1) and 87.48 (6) degrees , respectively, with the pyrazolo-[3,4-d]pyrimidine
      unit [maximum deviation = 0.052 (2) A]. An intra-molecular N-H?N hydrogen bond
      occurs. The crystal structure features N-H?O hydrogen bonds.

PMID- 23125692
TI  - 3,5,3',5'-Tetra-methyl-4,4'-bi(1H-pyrazol-yl) hemihydrate.
AB  - In the title compound, C(10)H(14)N(4).0.5H(2)O, the amino H atom of one of the
      two pyrazole rings is disordered over its two N atoms in a 1:1 ratio. The
      pyrazole rings are aligned at 60.1 (1) degrees . In the crystal, two bipyrazolyl
      mol-ecules are linked by an N-H?N hydrogen bond, generating a dimer; the dimer is
      connected to the water mol-ecule, which lies on a twofold rotation axis,
      resulting in the formation of a chain that makes an angle of ca 45.3 (1) degrees 
      with the ab plane. The chains are cross-linked by N-H?O and O-H?N inter-actions,
      forming a three-dimensional network.

PMID- 23125693
TI  - 2-(1,3-Dioxoisoindolin-2-yl)acetic acid-N'-[(E)-4-meth-oxy-benzyl-idene]pyridine
      4-carbohydrazide (2/1).
AB  - In the crystal structure of the title compound,
      2C(10)H(7)NO(4).C(14)H(13)N(3)O(2), the two independent acid mol-ecules are
      connected through strong O-H?N and O-H?O hydrogen bonds to the central mol-ecule
      of the anti-tubercular drug N'-[(E)-4-meth-oxy-benzyl-idene]pyridine-4
      carbohydrazide. Two such trimolecular units related by an inversion centre inter
      act through a pair of N-H?O hydrogen bonds, forming a 3 + 3 mol-ecular aggregate.
      The dihedral angle between the aromatic rings of the hydrazone mol-ecule is 1.99
      (12) degrees . The crystal packing features weak C-H?O and pi-pi stacking inter
      actions, with centroid-centroid distances of 3.8460 (19) and 3.8703 (13) A.

PMID- 23125694
TI  - (Dimethyl-phosphor-yl)methanaminium chloride.
AB  - The crystal structure of the title salt, C(3)H(11)NOP(+).Cl(-), is primarily
      built from centrosymmetric dimers of two cations, connected head-to-tail by two
      charge-supported strong N-H?O hydrogen bonds, with a graph-set descriptor R(2)
      (2)(10). The chloride counter-anions connect these dimeric cationic units into
      chains along the a-axis direction.

PMID- 23125695
TI  - Methyl (3S,3'R)-1-methyl-2,2''-dioxo-1',2',3',5',6',7',8',8a'-octa-hydro-dispiro
      [indoline-3,2'-indolizine-3',3''-indoline]-1'-carboxyl-ate.
AB  - In the title compound, C(25)H(25)N(3)O(4), the central pyrrolidine ring and the
      two pyrrolidine rings adopt twisted conformations, whereas the piperidine ring in
      the octa-hydro-indolizine fused ring system adopts a chair conformation. The
      indoline ring systems are almost perpendicular with respect to the mean plane of
      the octa-hydro-indolizine ring system, making dihedral angles of 84.4 (5) and
      79.4 (5) degrees . The acetate group attached to the octa-hydro-indolizine ring
      system assumes an extended conformation. In the crystal, N-H?O hydrogen bonds
      result in the formation of a helical C(7) chain running parallel to [101]. The
      crystal packing features C-H?O hydrogen bonds and C-H?pi inter-actions.

PMID- 23125696
TI  - Methyl (3R*,3'S*)-1',1''-dimethyl-2,2''-dioxodispiro-[indoline-3,2'-pyrrolidine
      3',3''-indoline]-4'-carboxyl-ate.
AB  - In the title compound, C(22)H(21)N(3)O(4), the central pyrrolidine ring adopts an
      envelope conformation with the N atom in the flap position. The indoline ring
      systems are almost perpendic-ular to the mean plane of the pyrrolidine ring,
      making dihedral angles of 86.4 (8) and 83.1 (8) degrees . The acetate group
      attached to the pyrrolidine ring assumes an extended conformation. In thecrystal,
      N-H?O hydrogen bonds result in the formation of a C(7) chain running along [100].
      The crystal packing also features pi-pi inter-actions [centroid-centroid distance
      = 3.2032 (11) A].

PMID- 23125697
TI  - N-(2-Chloro-phen-yl)-1-phenyl-formamido 3-(2-nitro-phen-yl)propano-ate.
AB  - In the title mol-ecule, C(22)H(17)ClN(2)O(5), the nitro-substituted benzene ring
      makes a dihedral angle of 79.22 (1) degrees  with the benzoyl ring and 53.03 (1)
      degrees  with the chloro-substituted benzene ring. An intra-molecular C-H?O
      hydrogen bond occurs. The crystal structure features weak C-H?Cl and C-H?O inter
      actions.

PMID- 23125698
TI  - 2-[(Phenyl-carbamo-yl)amino]-butyl N-phenyl-carbamate.
AB  - In the title compound, C(18)H(21)N(3)O(3), the terminal phenyl rings make a
      dihedral angle of 86.3 (5) degrees . In the crystal, mol-ecules are linked by N
      H?O hydrogen bonds into chains along [001], forming parallel C(4) and R(1) (2)(6)
      graph-set motifs.

PMID- 23125699
TI  - 5''-(2,4-Dichloro-benzyl-idene)-1'-(2,4-dichloro-phen-yl)-1''-methyl
      1',2',3',5',6',7',8',8a'-octa-hydro-dispiro-[acenaphthyl-ene-1,3'-indolizine
      2',3''-piperidine]-2,4''(1H)-dione.
AB  - In the title compound, C(37)H(30)Cl(4)N(2)O(2), the pyridinone ring adopts a
      twisted half-chair conformation. In the octa-hydro-indolizine fused-ring system,
      the piperidine ring is in a chair conformation and the pyrrole ring is twisted
      about the C-N bond linking the five- and six-membered rings. The mol-ecular
      structure features an intra-molecular C-H?O inter-action and the crystal packing
      is stabilized by C-H?pi inter-actions.

PMID- 23125700
TI  - 4'-(3-Bromo-phen-yl)-1'-methyl-dispiro-[indan-2,2'-pyrrolidine-3',2''-indan]
      1,3,1''-trione.
AB  - In the title compound, C(27)H(20)BrNO(3), two intra-molecular C-H?O hydrogen
      bonds both form S(6) rings. The pyrrolidine ring adopts a twisted conformation
      about the C-C bond bearing the indane ring systems. The other two five-membered
      rings within the indane systems are in shallow envelope conformations, with the
      spiro C atoms as the flap atoms. The mean plane of the pyrrolidine ring [maximum
      deviation = 0.275 (1) A] makes dihedral angles of 65.25 (7), 78.33 (6) and 75.25
      (6) degrees  with the bromo-substituted benzene ring and the mean planes of the
      mono- and dioxo-substituted indane rings, respectively. In the crystal, mol
      ecules are linked by C-H?O and C-H?N hydrogen bonds into a three-dimensional
      network. In addition, C-H?pi inter-actions are observed.

PMID- 23125702
TI  - 6-(4-Meth-oxy-phen-yl)-1,3,5-triazine-2,4-diamine.
AB  - In the title compound, C(10)H(11)N(5)O, the triazine ring forms a dihedral angle
      of 10.37 (4) degrees  with the benzene ring. In the crystal, adjacent mol-ecules
      are linked by a pair of N-H?N hydrogen bonds, forming an inversion dimer with an
      R(2) (2)(8) ring motif. The dimers are further connected via N-H?O and N-H?N
      hydrogen bonds, resulting in a three-dimensional network.

PMID- 23125701
TI  - (E)-1-[4-(Hex-yloxy)phen-yl]-3-(2-hy-droxy-phen-yl)prop-2-en-1-one.
AB  - In the title compound, C(21)H(24)O(3), the enone moiety adopts an s-cis
      conformation and the dihedral angle between the benzene rings is 12.89 (6)
      degrees . The hex-yloxy tail adopts an extended conformation. In the crystal,
      inversion dimers are linked by pairs of O-H?O hydrogen bonds and pairs of C-H?O
      inter-actions, forming two R(2) (2)(7) and one R(2) (2)(10) loops. The dimers are
      then arranged into sheets lying parallel to (201) and weak C-H?pi inter-actions
      consolidate the packing.

PMID- 23125703
TI  - (E)-1-(3-Hy-droxy-phen-yl)-3-[4-(tetra-dec-yl-oxy)phen-yl]prop-2-en-1-one.
AB  - In the title compound, C(29)H(40)O(3), the enone moiety adopts an s-cis
      conformation. The dihedral angle between the benzene rings is 4.33 (5) degrees 
      The least-squares mean line through the tetra-decyl side chain forms a dihedral
      angle of 83.99 (7) degrees  with the normal to the attached benzene ring. In the
      crystal, O-H?O and C-H?O hydrogen bonds involving the keto and the hy-droxy O
      atoms form ribbons along [-41-1]. The crystal structure also features C-H?pi
      inter-actions.

PMID- 23125704
TI  - 2,9,12,15,18,25,27,34,37,40,43,50-Dodeca-oxa-56-aza-hepta-cyclo
      [24.24.5.1(51,55).0(3,8).0(19,24).0(28,33).0(44,49)]hexa-penta-conta
      3,5,7,19(24),20,22,28(33),29,31,44,46,48,51,53,55-penta-deca-ene.
AB  - The title compound, C(43)H(45)NO(12), was prepared from the reaction of 2,6-bis
      (dibromo-meth-yl)pyridine and bis-phenol in the presence of caesium carbonate as
      a base. The central ring makes dihedral angles of 64.83 (6), 13.48 (6), 56.96 (6)
      and 66.21 (6) degrees  with the peripheral rings. In the crystal, mol-ecules are
      linked by weak C-H?O and C-H?pi inter-actions, forming a folded structure.

PMID- 23125705
TI  - 4-[4-(4-Chloro-benzo-yl)-2,3-diphenyl-isoxazolidin-5-yl]-1-(4-meth-oxy-phen-yl)-3
      phenyl-azetidin-2-one.
AB  - In the title compound, C(38)H(31)ClN(2)O(4), the isoxazole ring adopts an
      envelope conformation with the N atom as the flap. The crystal packing is
      stabilized by C-H?O hydrogen bonds, forming chains running along the c-axis
      direction.

PMID- 23125706
TI  - 3-(2-Acetamido-eth-yl)-1H-indol-5-yl 4-nitro-phenyl carbonate.
AB  - In the title mol-ecule, C(19)H(17)N(3)O(6), the indole ring system is essentially
      planar (r.m.s. deviation = 0.009 A) and forms a dihedral angle of 31.96 (9)
      degrees  with the nitro-substituted benzene ring. In the crystal, mol-ecules are
      linked by pairs of N-H?O hydrogen bonds, forming inversion dimers which are
      connected by further N-H?O hydrogen bonds into a two-dimensional network parallel
      to (102).

PMID- 23125707
TI  - N-[2-({[1-(4-Chloro-phen-yl)-1H-pyrazol-3-yl]-oxy}meth-yl)phen-yl]-N-meth-oxy
      hydrazinecarboxamide.
AB  - In the title compound, C(18)H(18)ClN(5)O(3), the hydrazinecarboxamide N-N-C(O)-N
      unit is nearly planar [maximum deviation = 0.074 (2) A] and is inclined at a
      dihedral angle of 57.43 (7) degrees  with respect to the plane of the attached
      benzene ring. The chloro-phenyl group makes dihedral angles of 19.71 (7) and
      34.07 (6) degrees  with the pyrazole and benzene rings, respectively. In the
      crystal, pairs of N-H?O hydrogen bonds link the mol-ecules into inversion dimers
      that are further linked into chains along the a-axis direction by N-H?N hydrogen
      bonds. In addition, pi-pi stacking inter-actions are observed between benzene
      rings [centroid-centroid distance = 3.680 (1) A].

PMID- 23125708
TI  - Ethyl 6-(4-bromo-phen-yl)-4-(4-fluoro-phen-yl)-2-oxocyclo-hex-3-ene-1-carboxyl
      ate.
AB  - There are two independent mol-ecules in the asymmetric unit of the title
      compound, C(21)H(18)BrFO(3), in which the dihedral angles between the fluoro
      phenyl and bromo-phenyl groups are 77.0 (1) and 85.8 (1) degrees . In one of the
      mol-ecules, two methine C-H groups of the cyclo-hexene ring are disordered over
      two sets of sites in a 0.53 (2):0.47 (2) ratio. In both mol-ecules, the atoms of
      the ethyl group were refined as disordered over two sets of sites with
      occupancies of 0.67 (2):0.33 (2) and 0.63 (4):0.37 (4). The cyclo-hexene rings
      have slightly distorted sofa conformations in both mol-ecules. In the crystal, C
      H?O inter-actions link mol-ecules into chains along the b axis.

PMID- 23125709
TI  - 1,5,7,8',11-Penta-meth-oxy-13H-spiro-[dibenzo[a,g]fluorene-13,1'(4'H)-naphthalen]
      4'-one toluene monosolvate.
AB  - In the title compound, C(35)H(28)O(6).C(7)H(8), the dihedral angle between the
      mean planes through the naphthalene ring systems of the dibenzo[a,g]fluorene
      moiety is 22.44 (3) degrees . The aromatic ring system of the naphthalenone unit
      is approximately perpendicular to the mean plane of the five-membered ring,
      forming a dihedral angle of 87.51 (5) degrees . An intra-molecular C-H?O hydrogen
      bond is observed. In the crystal, pairs of C-H?pi inter-actions link the mol
      ecules, forming inversion dimers.

PMID- 23125710
TI  - 6-Methyl-4-oxo-4H-chromene-3-carbaldehyde.
AB  - In the title compound, C(11)H(8)O(3), the benzopyran-4-one or chromone ring
      system is almost planar, with a maximum deviation of 0.045 (2) A. The crystal
      structure is stablized by pi-pi inter-actions between the benzene and pyran rings
      of inversion-related mol-ecules stacked along the b axis, with a centroid
      centroid distance of 3.5463 (12) A

PMID- 23125711
TI  - (E)-1-(5-Iodo-thio-phen-2-yl)-3-(3,4,5-trimeth-oxy-phen-yl)prop-2-en-1-one.
AB  - In the title compound, C(16)H(15)IO(4)S, the dihedral angle between the thio
      phene and benzene rings is 11.50 (2) degrees . The methoxy O atoms deviate by
      0.0060 (2), -0.1319 (2) and 0.0426 (2) A from the phenyl ring plane. The crystal
      packing features C-H?O hydrogen bonds, which link the molecules into C(11) chains
      propagating in [100xxx].

PMID- 23125712
TI  - 5-[(4-Fluoro-anilino)meth-yl]-6-methyl-N-(4-methyl-phen-yl)-2-phenyl-pyrimidin-4
      amine.
AB  - In the title compound, C(25)H(23)FN(4), the pyrimidine ring makes dihedral angles
      of 11.3 (2), 24.5 (2) and 70.1 (2) degrees  with the phenyl and two benzene
      rings, and the mol-ecular conformation is stabilized by an intra-molecular N-H?N
      hydrogen bond with an S(6) ring motif. In the crystal, a pair of weak C-H?F
      hydrogen bonds link two mol-ecules into an inversion dimer with an R(2) (2)(16)
      motif. In the dimer, there is also an inter-molecular pi-pi stacking inter-action
      [centroid-centroid distance = 3.708 (4) A] between the fluorinated benzene rings.
      The dimers are further linked by a C-H?pi inter-action, so forming a column along
      the c axis.

PMID- 23125713
TI  - N'-[(E)-4-Hy-droxy-benzyl-idene]-2-(naph-tha-len-2-yl-oxy)acetohydrazide.
AB  - The asymmetric unit of the title compound, C(19)H(16)N(2)O(3), contains two
      independent mol-ecules in which the dihedral angles between the naphthalene ring
      system and the benzene ring are 10.0 (1) and 35.3 (1) degrees . In the crystal,
      mol-ecules are linked by N-H?O and O-H?O hydrogen bonds, forming a two
      dimensional framework parallel to (001). Weak C-H?O and C-H?N hydrogen bonds
      complete a three-dimensional network.

PMID- 23125714
TI  - Bis(2-amino-pyrimidin-1-ium) sulfate.
AB  - In the title compound, 2C(4)H(6)N(3) (+).SO(4) (2-), the cations are each
      essentially planar with r.m.s. deviations of the fitted atoms of 0.008 and 0.002
      A. In the crystal, adjacent ions are linked by N-H?O, C-H?O and C-H?N hydrogen
      bonds, forming a three-dimensional network.

PMID- 23125715
TI  - 3-(2-Chloro-3-hy-droxy-4-meth-oxy-phen-yl)-1-(4,5-dimeth-oxy-2-methyl-phen
      yl)prop-2-en-1-one.
AB  - The title compound, C(19)H(19)ClO(5), is a chloro derivative of a biologically
      significant chalcone family. The mean plane of the two substituted benzene rings
      are twisted by 55.33 (8) degrees  with respect to each other. An intra-molecular
      C-H?Cl hydrogen bond generates an S(5) graph-set motif. In the crystal, a
      bifurcated O-H?(O,O) hydrogen bond leads to an R(1) (2)(5) graph-set motif and to
      the formation of zigzag chains propagating along the c-axis direction. A weak pi
      pi inter-action involving the methyl-phenyl rings [centroid-centroid distance =
      3.8185 (10) A] and C-H?pi inter-actions also occur.

PMID- 23125716
TI  - 3-Chloro-meth-yl-2-hy-droxy-benzaldehyde.
AB  - In the title compound, C(8)H(7)ClO(2), the hydroxyl and aldehyde groups are co
      planar with the benzene ring [maximum deviation 0.018 (3) A], and the Cl-C-C
      plane is almost perpendicular to the benzene ring [dihedral angle 83.7 (2)
      degrees ]. An intra-molecular O-H?O hydrogen bond occurs between the hydroxyl and
      aldehyde groups.

PMID- 23125717
TI  - N-[4-(Azetidin-1-ylsulfon-yl)phen-yl]-N-(2,4-difluoro-benz-yl)acetamide.
AB  - In the title mol-ecule, C(18)H(18)F(2)N(2)O(3)S, the dihedral angle between the
      benzene rings is 79.40 (11) degrees . The 2,4-difluoro-benzyl and azetidine
      fragments adopt a trans arrangement relative to the central benzene ring. In the
      crystal, weak C-H?O hydrogen bonds connect mol-ecules into a two-dimensional
      network parallel to (001).

PMID- 23125718
TI  - 4-(2,3-Dimethyl-anilino)pent-3-en-2-one.
AB  - In the title compound, C(13)H(17)NO, the dihedral angle between the aryl ring and
      the amino-acryl-aldehyde mean plane [N-C=C-C=O; maximum deviation = 0.0144 (9) A]
      is 53.43 (4) degrees . There is an intra-molecular N-H?O hydrogen bond involving
      the amine and carbonyl groups. In the crystal, mol-ecules are linked by C-H?O
      hydrogen bonds, forming chains propagating along [001].

PMID- 23125719
TI  - Paliperidonium nitrate.
AB  - In the title mol-ecular salt (systematic name: 3-{2-[4-(6-fluoro-1,2-benzoxazol-3
      yl)piperidin-1-yl]eth-yl}-9-hy-droxy-2-methyl-1,6,7,8,9,9a-hexa-hydro-pyrido[1,2
      a]pyrimidin-4-one nitrate), C(23)H(29)FN(4)O(3) (+).NO(3) (-), the piperidine
      ring displays a chair conformation and its N atom is protonated; the N-H bond is
      in an axial orientation. The ring bearing the hy-droxy group exhibits a half
      chair conformation. The hy-droxy group as well as the adjacent methyl-ene group
      are disordered over two sets of sites in a 0.823 (5):0.177 (5) ratio. In the
      crystal, O-H?N, O-H?O, N-H?O and N-H?N hydrogen bonds connect the components into
      a three-dimensional network.

PMID- 23125720
TI  - Acetyl-ene-ammonia-18-crown-6 (1/2/1).
AB  - The title compound, C(2)H(2).C(12)H(24)O(6).2NH(3), was formed by co
      crystallization of 18-crown-6 and acetyl-ene in liquid ammonia. The 18-crown-6
      mol-ecule has threefold rotoinversion symmetry. The acteylene mol-ecule lies on
      the threefold axis and the whole mol-ecule is generated by an inversion center.
      The two ammonia mol-ecules are also located on the threefold axis and are related
      by inversion symmetry. In the crystal, the ammonia mol-ecules are located below
      and above the crown ether plane and are connected by inter-molecular N-H?O
      hydrogen bonds. The acetyl-ene mol-ecules are additionally linked by weak C-H?N
      inter-actions into chains that propagate in the direction of the crystallographic
      c axis. The 18-crown-6 mol-ecule [occupancy ratio 0.830 (4):0.170 (4)] is
      disordered and was refined using a split model.

PMID- 23125721
TI  - Diphenyl (methyl-amido)-phosphate.
AB  - The N-H bond in the title compound, C(13)H(14)NO(3)P, is syn-oriented relative to
      the P=O bond. The N atom deviates somewhat from planarity, the sum of the bond
      angles being 353.3 degrees . The P atom has a distorted tetra-hedral
      coordination; its bond angles are in the range 93.96 (5)-116.83 (6) degrees . In
      the crystal, mol-ecules form centrosymmetric dimers through P=O?H-N hydrogen
      bonds.

PMID- 23125722
TI  - (E)-1-(4-Decyl-oxyphen-yl)-3-(2-hy-droxy-phen-yl)prop-2-en-1-one.
AB  - In the title compound, C(25)H(32)O(3), the enone group adopts an s-cis
      conformation. The alk-oxy chain is in an all-trans conformation. The dihedral
      angle between the benzene rings is 7.86 (5) degrees . In the crystal, mol-ecules
      are connected by pairs of O-H?O hydrogen bonds, forming inversion dimers and
      giving R(2) (2)(10) rings. Within these dimers, weak C-H?O hydrogen bonds form
      two R(2) (2)(7) rings. In the crystal, the approximately planar mol-ecules
      [largest deviation for an atom being 0.4737 (12) A for the terminal C atom of the
      alk-oxy chain] are arranged in sheets parallel to (20-1). Weak C-H?pi inter
      actions are also observed.

PMID- 23125723
TI  - 1-(2-Carb-oxy-eth-yl)-5-ethyl-2-methyl-pyridinium chloride.
AB  - In the crystal structure of the title salt, C(11)H(16)NO(2) (+).Cl(-), the
      cations and anions are linked by O-H?Cl hydrogen bonds. The structure is further
      stabilized by weak C-H?Cl hydrogen bonds.

PMID- 23125724
TI  - Adipic acid-2,4-diamino-6-(4-meth-oxy-phen-yl)-1,3,5-triazine (1/2).
AB  - The asymmetric unit of the title compound, 2C(10)H(11)N(5)O.C(6)H(10)O(4),
      consists of a 2,4-diamino-6-(4-meth-oxy-phen-yl)-1,3,5-triazine mol-ecule and one
      half mol-ecule of adipic acid which lies about an inversion center. The triazine
      ring makes a dihedral angle of 12.89 (4) degrees  with the adjacent benzene ring.
      In the crystal, the components are linked by N-H?O and O-H?N hydrogen bonds, thus
      generating a centrosymmetric 2 + 1 unit of triazine and adipic acid mol-ecules
      with R(2) (2)(8) motifs. The triazine mol-ecules are connected to each other by N
      H?N hydrogen bonds, forming an R(2) (2)(8) motif and a supra-molecular ribbon
      along the c axis. The 2 + 1 units and the supra-molecular ribbons are further
      inter-linked by weak N-H?O, C-H?O and C-H?pi inter-actions, resulting in a three
      dimensional network.

PMID- 23125725
TI  - N-[2-(Phenyl-sulfon-yl)eth-yl]benzyl-amine.
AB  - The title compound, C(15)H(17)NO(2)S, exhibits intra-molecular hydrogen bonding
      between the amine H atom and a sulfonyl O atom. The conformation of the mol-ecule
      is described by the four PhCH(2)-NH-CH(2)-CH(2)-SO(2)Ph torsion angles of 79.6
      (2), -166.21 (14), -70.29 (17) and -58.93 (13) degrees .

PMID- 23125726
TI  - 1-(5-Amino-2,4-dinitro-phen-yl)pyridinium chloride monohydrate.
AB  - In the cation of the title hydrated salt, C(11)H(9)N(4)O(4) (+).Cl(-).H(2)O, the
      six-membered rings are inclined to each other at 79.0 (1) degrees  and an intra
      molecular N-H?O hydrogen bond occurs. In the crystal, N-H?Cl hydrogen bonds link
      two cations and two anions into centrosymmetric group, and O-H?Cl hydrogen bonds
      involving the water mol-ecules further link these groups into chains in [101]. An
      O-H?O inter-action is also present. The water mol-ecule is disordered over two
      sets of sites in a 0.555 (13):0.445 (13) ratio.

PMID- 23125727
TI  - (E)-2-[(2-Amino-phen-yl)imino-meth-yl]-4,6-di-tert-butyl-phenol.
AB  - In the title compound, C(21)H(28)N(2)O, the dihedral angle between the rings is
      35.2 (2) degrees . A weak intra-molecular O-H?N hydrogen bond is observed between
      the O-H H atom and the imine N atom. In the crystal, mol-ecules are linked by
      additional inter-molecular N-H?O hydrogen bonding, resulting in a wave-like chain
      along the b-axis direction.

PMID- 23125728
TI  - 1-[(2-Methyl-piperidin-1-yl)(phen-yl)meth-yl]naphthalen-2-ol.
AB  - In the title compound, C(23)H(25)NO, an intra-molecular O-H?N hydrogen bond
      defines the mol-ecular conformation; the naphthol mean plane and the benzene ring
      form a dihedral angle of 75.8 (2) degrees . The piperidine ring adopts a chair
      conformation. The crystal packing exhibits no short inter-molecular contacts.

PMID- 23125729
TI  - 2-(2H-Benzotriazol-2-yl)-6-[(dicyclo-hexyl-amino)-meth-yl]-4-(2,4,4-trimethyl
      pentan-2-yl)phenol.
AB  - In the title mol-ecule, C(33)H(48)N(4)O, the dihedral angle between the mean
      planes of the benzotriazole ring system [maximun deviation = 0.038 (2) A] and the
      phenol ring is 16.6 (2) degrees . There is an intra-molecular O-H?N hydrogen bond
      between the phenol and benzotriazole groups.

PMID- 23125730
TI  - Penta-cyclo-[8.2.1.1(4,7).0(2,9).0(3,8)]tetra-deca-5,11-diene.
AB  - The title compound, C(14)H(16), was prepared through [2 + 2] cyclo-addition of
      norbornadiene. There are two independent mol-ecules in the asymmetric unit: each
      is centrosymmetric with the centroid of the four-membered ring located about an
      inversion center. Each mol-ecule possesses an exo-trans-exo conformation.

PMID- 23125731
TI  - 2,4-Bis(2-bromo-phen-yl)-7-tert-pentyl-3-aza-bicyclo-[3.3.1]nonan-9-one.
AB  - The title compound, C(25)H(29)Br(2)NO, is a tert-pentyl analog of 2,4-bis-(2
      bromo-phen-yl)-3-aza-bicyclo-[3.3.1]nonan-9-one [Par-thiban et al. (2008 ?). Acta
      Cryst. E64, o2385]. Similar to its analog, the title compound exists in a twin
      chair conformation with an equatorial orientation of the 2-bromo-phenyl groups.
      The benzene rings are inclined to each other at a dihedral angle of 29.6 (3)
      degrees . The tert-pentyl group on the cyclo-hexa-none ring also adopts an
      exocyclic equatorial disposition.

PMID- 23125732
TI  - 4-Acetyl-1H-pyrrole-2-carbaldehyde.
AB  - The title compound, C(7)H(7)NO(2), was synthesized via a one-pot Vilsmeier-Haack
      and subsequent Friedel-Crafts reaction. The pyrazole ring makes dihedral angles
      of 4.50 (9) and 2.06 (8) degrees , respectively, with the aldehyde and acetyl
      groups. In the crystal, classical N-H?O hydrogen bonds and weak C-H?O inter
      actions assemble the mol-ecules into a chain along the b axis.

PMID- 23125733
TI  - Ethyl (E)-3-(6-methyl-4-oxo-4H-chromen-3-yl)prop-2-enoate.
AB  - In the title compound, C(15)H(14)O(4), the chromone ring system is close to being
      planar [maximum deviation = 0.015 (2) A]. The double bond of the ethyl prop-2
      enoate chain adopts an E conformation and an intra-molecular C-H?O hydrogen bond
      generates an S6 ring. In the crystal, inversion dimers linked by pairs of C-H?O
      hydrogen bonds generate R(2) (2)(14) loops. Weak pi-pi inter-actions [centroid
      centroid distance = 3.8493 (12) A] also occur.

PMID- 23125734
TI  - (2S*,3S*,3aS*,6S*,7aR*)-3-Hy-droxy-2-[(2R*,3S*)-3-isopropyl-oxiran-2-yl]-3,6
      dimethyl-3,3a,5,6,7,7a-hexa-hydro-1-benzofuran-4(2H)-one.
AB  - In the title compound, C(15)H(24)O(4), the six-membered ring shows a distorted
      chair conformation and the five-membered ring adopts an envelope conformation
      with the C atom bearing the methyl and OH groups as the flap. In the crystal, O
      H?O hydrogen bonds link the mol-ecules into chains running along the a-axis
      direction.

PMID- 23125735
TI  - [2-(Biphenyl-4-yl)-1,3-thia-zol-4-yl]methanol.
AB  - In the title compound, C(16)H(13)NOS, the central benzene ring makes dihedral
      angles of 3.25 (7) and 41.32 (8) degrees , respectively, with the thia-zole and
      phenyl rings. In the crystal, O-H?N hydrogen bonds link the mol-ecules into a
      chain along the c axis. A weak C-H?O inter-action further connects the chains
      into a layer parallel to the ac plane.

PMID- 23125736
TI  - Methyl 3-[(1,1-dioxo-1lambda(6),2-benzothiazol-3-yl)amino]-5-nitrothiophene-2
      carboxyl-ate.
AB  - The title nitro-thio-phene compound, C(13)H(9)N(3)O(6)S(2), crystallizes with two
      independent mol-ecules in the asymmetric unit; the mol-ecular structure of each
      is stabilized by an intra-molecular N-H?O hydrogen bond. The two mol-ecules adopt
      flattened but slightly different conformations, viz. the dihedral angle between
      the thio-phene ring and the essentailly planar 1,2-benzisothia-zole fragment
      (r.m.s. deviations = 0.0227 and 0.0108 A, respectively) is 15.62 (11) degrees  in
      one mol-ecule and 5.46 (11) degrees  in the other. In the crystal, mol-ecules are
      arranged into layers parallel to (-111) with weak C(ar)-H?O inter-actions formed
      within the layer. N-H?O hydrogen bonds also occur. There are pi-pi stacking inter
      actions between the mol-ecules in neighbouring layers, the distance between the
      centroids of the 1,2-benzisothia-zole benzene rings being 3.8660 (16) A.
      Moreover, dipolar S=O?C=O inter-actions with an O?C distance of 2.893 (3) A are
      observed between the symmetry-independent mol-ecules in different layers. The
      title compound showed weak inhibition of HLE (human leukocyte elastase).

PMID- 23125737
TI  - N,N-Dicyclo-hexyl-3,5-dinitro-benzamide.
AB  - In the title compound, C(19)H(25)N(3)O(5), the benzene ring is not coplanar with
      the amide group [dihedral angle = 61.90 (5) degrees ]. The cyclo-hexyl rings are
      in chair conformations. There is a strong inter-molecular inter-action between
      the C=O group of the amide group and the nitro group of an adjoining mol-ecule,
      with a short O?N distance of 2.7862 (17) A. In the crystal, C-H?O inter-actions
      occur along the [100] direction.

PMID- 23125738
TI  - N-(4-Chloro-phen-yl)-1-(5-{[(2-phenyl-ethen-yl)sulfon-yl]meth-yl}-1,3,4-oxadiazol
      2-yl)methane-sulfonamide.
AB  - In the title compound, C(18)H(16)ClN(3)O(5)S(2), the dihedral angles between the
      oxadiazole ring and the phenyl and chloro-benzene rings are 23.4 (2) and 45.4 (2)
      degrees , respectively. The C-S-N-C and C(ox)-C-S-C (ox = oxadiazole) torsion
      angles are 89.3 (5) and -69.1 (3) degrees , respectively. A short intra-molecular
      C-H?O contact closes an S(6) ring. In the crystal, mol-ecules are linked by N-H?O
      hydrogen bonds, generating C(10) chains propagating in [001]. The packing is
      consolidated by C-H?O, C-H?pi and very weak aromatic pi-pi stacking inter-actions
      [centroid-centroid separation = 4.085 (2) A].

PMID- 23125739
TI  - 4-Eth-oxy-benzohydrazide.
AB  - The title compound, C(9)H(12)N(2)O(2), is approximately planar (r.m.s. deviation
      = 0.13 A for all non-H atoms). The carbonyl O atom is involved as acceptor in
      three different hydrogen-bond inter-actions. One N-H?O and the C-H?O(carbonyl)
      contact together with a weak C-H?O(eth-oxy) interaction link the mol-ecules into
      sheets parallel to (102). These are further linked into a three-dimensional
      network via the remaining C-H?O(carbon-yl) hydrogen bond and a C(methyl-ene)-H?pi
      inter-action.

PMID- 23125740
TI  - 3-Benzyl-5-methyl-1,2-benzoxazole 2-oxide.
AB  - In the title compound, C(15)H(13)NO(2), the isoxazole unit and the attached
      benzene ring are almost coplanar, making a dihedral angle of 1.42 (8) degrees .
      The benzyl ring is inclined to the isoxazole ring by 74.19 (8) degrees  and is in
      a +sc conformation with respect to the benzisoxazole unit. In the crystal, C-H?O
      hydrogen bonds link the mol-ecules, forming zigzag chains propagating along the b
      axis. There are also pi-pi inter-actions present involving the isoxazole and
      benzyl rings [centroid-centroid distance = 3.5209 (10) A], and C-H?pi inter
      actions involving the benzene ring of the benzoisoxazole unit and the methyl-ene
      bridging group.

PMID- 23125741
TI  - 4-{(E)-2-[4-(But-3-en-1-yl-oxy)phen-yl]diazen-1-yl}benzoic acid.
AB  - The title compound, C(17)H(16)N(2)O(3), has an E conformation about the
      azobenzene (-N=N-) linkage. The benzene rings are twisted slightly with respect
      to each other [6.79 (9) degrees ], while the dihedral angle between the plane
      through the carb-oxy group and the attached benzene ring is 3.2 (2) degrees . In
      the crystal, mol-ecules are oriented with the carb-oxy groups head-to-head,
      forming O-H?O hydrogen-bonded inversion dimers. These dimers are connected by C
      H?O hydrogen-bonds into layers lying parallel to the (013) plane.

PMID- 23125742
TI  - l-Leucinium fluoride monohydrate.
AB  - The asymmetric unit of the title hydrated salt, C(6)H(14)NO(2) (+).F(-).H(2)O,
      contains a discrete cation with a protonated amino group, a halide anion and one
      water mol-ecule. The crystal structure is composed of double layers parallel to
      (010) held together by N-H?O, N-H?F, O-H?F and C-H?F hydrogen bonds, forming a
      two-dimensional network, and stacked along the c axis, viz. hydro-philic layers
      at z = 0 and 1/2 and hydro-phobic layers at z = 1/3 and 2/3.

PMID- 23125743
TI  - Tetra-methyl 1,4-dimethyl-13,14-dioxa-penta-cyclo
      [8.2.1.1(4,7).0(2,9).0(3,8)]tetra-deca-5,11-diene-5,6,11,12-tetra-carboxyl-ate.
AB  - In the title compound, C(22)H(24)O(14), the relative stereochemistry at the cyclo
      butane ring is cis-anti-cis and the methyl groups in the bicyclic rings are syn
      to each other. The two carboxyl-ate groups attached to the same -C=C- bond are
      disordered over two sets of sites in a 0.603 (2):0.397 (2) ratio. In the crystal,
      weak C-H?O hydrogen bonds connect mol-ecules into C(12) chains along [001]
      incorporating R(2) (2) (2)(10) rings.

PMID- 23125744
TI  - Tetra-tert-butyl 13,14-dioxapenta-cyclo-[8.2.1.1(4,7).0(2,9).0(3,8)]tetra-deca
      5,11-diene-5,6,11,12-tetra-carboxyl-ate.
AB  - The stereochemistry of the title compound, C(32)H(44)O(10), at the cyclo-butane
      ring is cis-anti-cis. The mol-ecule lies across an inversion center. In the
      crystal, weak C-H?O hydrogen bonds connect mol-ecules into chains along [100],
      forming R(2) (2)(6) rings.

PMID- 23125745
TI  - Hexamethyl 13,14-dioxapenta-cyclo-[8.2.1.1(4,7).0(2,9).0(3,8)]tetra-deca-5,11
      diene-1,4,5,6,11,12-hexa-carboxyl-ate.
AB  - In the title compound, C(24)H(24)O(14), the stereochemistry at the cyclo-butane
      ring is cis-anti-cis and the -COOMe groups in the bicyclic rings are syn to each
      other. The mol-ecule lies on a twofold rotation axis. In the crystal, weak C-H?O
      hydrogen bonds connect mol-ecules into chains along [001], forming R(2) (2)(10)
      rings.

PMID- 23125746
TI  - Bis(2-methyl-1H-benzimidazol-3-ium) naphthalene-1,5-disulfonate.
AB  - The asymmetric unit of the title compound, 2C(8)H(9)N(2) (+).C(10)H(6)O(6)S(2) (2
      ), contains a 2-methyl-benzimidazolium cation and one half of a naphthalene-1,5
      disulfonate anion. The formula unit is generated by an inversion center. In the
      crystal, N-H?O hydrogen bonds link the components into chains along [001]. In
      addition, weak C-H?O hydrogen bonds and weak C-H?pi inter-actions are observed.
      The methyl H atoms were refined as disordered over two sets of sites with equal
      occupancy.

PMID- 23125747
TI  - 3-Ethyl-sulfinyl-2-(3-fluoro-phen-yl)-5-iodo-7-methyl-1-benzofuran.
AB  - In the title compound, C(17)H(14)FIO(2)S, the 3-fluoro-phenyl ring makes a
      dihedral angle of 14.56 (5) degrees  with the mean plane [r.m.s. deviation =
      0.012 (1) A] of the benzofuran fragment. In the crystal, mol-ecules are linked
      via pairs of I?O contacts [3.038 (2) A], forming inversion dimers. In the 3
      fluoro-phenyl ring, the F atom is disordered over two positions, with site
      occupancy factors of 0.747 (3) and 0.253 (3).

PMID- 23125748
TI  - N-(Naphthalen-1-yl-methyl-idene)-4H-1,2,4-triazol-4-amine.
AB  - In the title mol-ecule, C(13)H(10)N(4), the dihedral angle between the triazole
      ring and the naphthalene ring system is is 56.1 (2) degrees . In the crystal, mol
      ecules are connected by weak C-H?N hydrogen bonds into chains along [100]. A
      short intra-molecular C-H?N contact is also observed.

PMID- 23125749
TI  - Ethyl 2-[4-(morpholin-4-yl)phen-yl]-1-[3-(2-oxopyrrolidin-1-yl)prop-yl]-1H-1,3
      benzimidazole-5-carboxyl-ate monohydrate.
AB  - The asymmetric unit of the title compound, C(27)H(32)N(4)O(4).H(2)O, contains two
      independent benzimidazole-5-carboxyl-ate mol-ecules and two water mol-ecules. In
      both main mol-ecules, the pyrrolidine rings are in an envelope conformation with
      a methyl-ene C atom as the flap. The morpholine rings adopt chair conformations.
      Both benzimidazole rings are essentially planar, with maximum deviations of 0.008
      (1) A, and form dihedral angles of 37.65 (6) and 45.44 (6) degrees  with the
      benzene rings. In one mol-ecule, an intra-molecular C-H?O hydrogen bond forms an
      S(7) ring motif. In the crystal, O-H?O and O-H?N hydrogen bonds connect pairs of
      main mol-ecules and pairs of water mol-ecules into two independent
      centrosymmetric four-compoment aggregates. These aggregates are connect by C-H?O
      hydrogen bonds leading to the formation of a three-dimensional network, which is
      stabilized by C-H?pi interactions.

PMID- 23125750
TI  - 5-Chloro-N-{4-oxo-2-[4-(trifluoro-meth-yl)phen-yl]-1,3-thia-zolidin-3-yl}-3
      phenyl-1H-indole-2-carboxamide.
AB  - In the title compound, C(25)H(17)ClF(3)N(3)O(2)S, the five-membered 1,3-thia
      zolidine ring adopts a twist conformation. The three F atoms of the CF(3) group
      are disordered over two sets of sites with refined occupancies of 0.542 (18) and
      0.458 (18). In the nine-membered 1H-indoline ring system, the 1H-pyrrole ring
      forms a dihedral angle of 4.7 (2) degrees  with the benzene ring, while it is
      twisted at an angle of 46.5 (2) degrees  with respect to the attached phenyl
      ring. The dihedral angle between the phenyl and trifluoro-methyl-substituted
      benzene rings is 56.0 (2) degrees . In the crystal, N-H?O hydrogen bonds connect
      the mol-ecules into a three-dimensional network. In addition, weak C-H?O hydrogen
      bonds and weak C-H?pi inter-actions are observed.

PMID- 23125751
TI  - (4Z)-1-Methyl-4-[(2E)-2-(4-methyl-benzyl-idene)hydrazin-1-yl-idene]-3,4-dihydro
      1H-2lambda(6),1-benzothia-zine-2,2-dione.
AB  - In the title compound, C(17)H(17)N(3)O(2)S, the dihedral angle between the
      aromatic rings is 6.3 (5) degrees  and the C=N-N=C group is statistically planar
      [torsion angle = 179.8 (8) degrees ]. The conformation of the thia-zine ring is
      an envelope, with the S atom displaced by 0.823 (9) A from the mean plane of the
      other five atoms (r.m.s. deviation = 0.012 A). In the crystal, C-H?O inter
      actions link the mol-ecules into C(5) chains propagating along [101]. The chains
      are consolidated by weak aromatic pi-pi stacking between the benzene and toluene
      rings [centroid-to-centroid separation = 3.826 (5) A and inter-planar angle = 6.3
      (4) degrees ].

PMID- 23125752
TI  - (E)-N'-[1-(Thio-phen-2-yl)ethyl-idene]isonicotinohydrazide.
AB  - In the title compound, C(12)H(11)N(3)OS, the dihedral angle between the pyridine
      and thio-phene rings is 46.70 (9) degrees  and the C-N-N-C torsion angle is
      178.61 (15) degrees . In the crystal, inversion dimers linked by pairs of N-H?O
      hydrogen bonds generate R(2) (2)(8) loops.

PMID- 23125753
TI  - N-(2,3-Dimethyl-phen-yl)-4-fluoro-N-[(4-fluoro-phen-yl)sulfon-yl]benzene
      sulfonamide.
AB  - In the title compound, C(20)H(17)F(2)NO(4)S(2), the dihedral angles between the o
      xylene ring and the fluoro-benzene rings are 31.7 (1) and 32.8 (1) degrees , and
      the dihedral angle between the fluoro-benzene rings is 50.9 (1) degrees . The C-N
      S-C torsion angles are 76.7 (2) and 101.8 (2) degrees . In the crystal, mol
      ecules are connected by C-H?O inter-actions into sheets in the ab plane.

PMID- 23125754
TI  - N-(4-Methyl-phen-yl)-N-{[(2-nitro-phen-yl)acet-yl]-oxy}benzamide.
AB  - In the title mol-ecule, C(22)H(18)N(2)O(5), the nitro-substituted benzene ring
      makes dihedral angles of 71.56 (1) degrees  with the benzoyl ring and 16.28 (1)
      degrees  with the methyl-substituted benzene ring. The crystal structure features
      C-H?O inter-actions, which generate chains.

PMID- 23125755
TI  - N-[2,6-Bis(1-methyl-eth-yl)phen-yl]pyridine-4-carboxamide.
AB  - In the title compound, C(18)H(22)N(2)O, the dihedral angle between the benzene
      ring and the pyridine ring is 80.0 (1) degrees . In the crystal, N-H?O hydrogen
      bonds connect the mol-ecules into chains along the b axis. The packing also
      features C-H?O and C-H?N hydrogen bonds and C-H?pi interactions, one directed to
      the benzene ring and the other to the center of the pyridine ring.

PMID- 23125756
TI  - Methyl (E)-2-[(3-chloro-4-cyano-phenyl)-imino]-4-(4-chloro-phen-yl)-6-methyl
      1,2,3,4-tetra-hydro-pyrimidine-5-carboxyl-ate.
AB  - In the title compound, C(20)H(16)Cl(2)N(4)O(2), the dihedral angles between the
      planes of the chloro-phenyl, chloro-cyano-phenyl-imine and ester groups and the
      plane of the six-membered tetra-hydro-pyrimidine ring are 86.9 (2), 72.6 (2) and
      7.9 (2) degrees , respectively. The Cl atom substituent on the cyano-phenyl ring
      is disordered over two rotationally related sites [occupancy factors 0.887
      (2):0.113 (2)], while the mol-ecular conformation is stabilized by the presence
      of an intra-molecular aromatic C-H?pi inter-action. Both N-H groups participate
      in separate inter-molecular hydrogen-bonding associations with centrosymmetric
      cyclic motifs [graph sets R(2) (2)(8) and R(2) (2)(12)], resulting in ribbons
      parallel to [010]. Further weak C-H?O hydrogen bonds link these ribbons into a
      two-dimensional mol-ecular assembly.

PMID- 23125757
TI  - 2-(3,4-Dimeth-oxy-phen-yl)-4,5-diphenyl-1-(prop-2-en-1-yl)-1H-imidazole.
AB  - In the title compound, C(26)H(24)N(2)O(2), the planar 1H-imidazole ring makes
      dihedral angles of 35.78 (4), 26.35 (5) and 69.75 (5) degrees , respectively,
      with the dimeth-oxy-phenyl ring and the phenyl rings in the 4- and 5-positions.
      In the crystal, C-H?O hydrogen bonds connect neighbouring mol-ecules, forming
      infinite chains running along the b axis. Furthermore, the crystal structure
      exhibits a C-H-?pi inter-action between a methyl H atom and a phenyl ring from an
      adjacent mol-ecule.

PMID- 23125758
TI  - 5''-Benzyl-idene-1''-methyl-1'-phenyl-1',2',3',5',6',7',8',8a'-octa-hydro
      dispiro[acenaphthyl-ene-1,3'-indolizine-2',3''-piperidine]-2,4''(1H)-dione.
AB  - In the title compound, C(37)H(34)N(2)O(2), the pyridinone ring adopts a half
      chair conformation. In the octa-hydro-indolizine fused-ring system, the
      piperidine ring is in a chair conformation and the pyrrole ring is twisted about
      the N-C(piperidine) bond. The mol-ecular structure features a weak intra
      molecular C-H?O inter-action.

PMID- 23125759
TI  - N-Ethyl-2-[1-(2-hy-droxy-6-meth-oxy-phenyl)ethyl-idene]hydrazinecarbothio-amide.
AB  - In the title compound, C(12)H(17)N(3)O(2)S, the dihedral angle between the mean
      planes of the hydrazinecarbothio-amide group and the benzene ring is 86.8 (4)
      degrees . In the crystal, inter-molecular O-H?S hydrogen bonds link the mol
      ecules into chains along [001]. The crystal studied was an inversion twin, the
      refined ratio of the twin components being 0.98021 (3):0.01978 (7).

PMID- 23125760
TI  - 2,6-Dimethyl-pyridinium bromide.
AB  - The asymmetric unit of the title salt, C(7)H(10)N(+).Br(-), comprises two 2,6
      dimethyl-pyridinium cations and two bromide anions. One cation and one anion are
      situated in general positions, while the other cation and the other anion lie on
      a crystallographic mirror plane parallel to (010). Each pair of ions inter-act
      via N-H?Br and C-H?Br hydrogen bonding, generating motifs depending on the cation
      and anion involved. Thus, the cation and the anion on the mirror plane generate
      infinite chains along the c axis, while the other ionic pair leads to sheets
      parallel to the ac plane. In the overall crystal packing, both motifs alternate
      along the b axis, with a single layer of the chain motif sandwiched between two
      double layers of the sheet motif. The sheets and chains are further connected via
      aryl pi-pi inter-actions [centroid-centroid distances = 3.690 (2) and 3.714 (2)
      A], giving a three-dimensional network.

PMID- 23125761
TI  - (2E)-2-[1-(2-Hy-droxy-4-meth-oxy-phenyl)ethyl-idene]-N-phenyl-hydrazine-carbox
      amide monohydrate.
AB  - The title compound, C(16)H(17)N(3)O(3).H(2)O, exists in the E conformation with
      respect to the azomethine C=N double bond. While the phenyl ring is almost
      coplanar with the central hydrazinecarboxamide group [dihedral angle = 14.18 (11)
      degrees ], it is twisted slightly with respect to the other aromatic ring in the
      mol-ecule, with a dihedral angle of 22.88 (13) degrees . The packing is dominated
      by O-H?O, N-H?O and C-H?O hydrogen-bond inter-actions, forming a three
      dimensional supra-molecular structure which is augmented by two types of C-H?pi
      inter-actions. An intramolecular O-H?N interaction is also present in the
      molecule.

PMID- 23125762
TI  - 2-(4-Meth-oxy-phenyl)-2-oxoethan-aminium chloride.
AB  - In the cation of the title compound, C(9)H(12)NO(2) (+).Cl(-), the dihedral angle
      between the 2-oxoethanaminium N-C-C(=O)- plane [maximum deviation = 0.0148 (12)
      A] and the benzene ring is 7.98 (8) degrees . The meth-oxy group is approximately
      in-plane with the benzene ring, with a C-O-C-C torsion angle of -2.91 (18)
      degrees . In the crystal, the cations and chloride anions are connected by N-H?Cl
      and C-H?Cl hydrogen bonds, forming a layer parallel to the bc plane. A C-H?pi
      inter-action further links the layers.

PMID- 23125763
TI  - (E)-N'-(4-Meth-oxy-benzyl-idene)-2-(2-methyl-4-nitro-1H-imidazol-1
      yl)acetohydrazide.
AB  - In the title compound, C(14)H(15)N(5)O(4), the central -C=N-N-C(=O)-C- bridge is
      nearly planar [maximum deviation = 0.037 (1) A] and forms dihedral angles of 7.37
      (9) and 73.33 (5) degrees , respectively, with the benzene and imidazole rings.
      The dihedral angle between the benzene and imidazole rings is 66.08 (9) degrees .
      The meth-oxy and nitro groups are nearly coplanar with the benzene and imidazole
      rings, respectively, with a C-O-C-C torsion angle of 5.9 (2) degrees  and an O-N
      C-C angle of -0.2 (2) degrees . In the crystal, mol-ecules are linked by a pair
      of N-H?O hydrogen bonds with an R(2) (2)(8) ring motif, forming an inversion
      dimer. The dimers are further inter-connected by C-H?O hydrogen bonds into a
      sheet parallel to the (111) plane. A C-H?pi inter-action is also observed between
      the sheets.

PMID- 23125764
TI  - 2,2'-Diethoxy-4,4'-[(E,E)-hydrazine-diyl-idenebis(methanylylidene)]diphenol.
AB  - The complete molecule of the title compound, C(18)H(20)N(2)O(4), is generated by
      inversion symmetry. The conformation around the C=N bond is E. With the exception
      of the eth-oxy substituent, the mol-ecule is essentially planar with an r.m.s.
      deviation of 0.0455 A. In the crystal, mol-ecules are linked by O-H?N hydrogen
      bonds into a two-dimensional supra-molecular network parallel to the bc plane.

PMID- 23125765
TI  - 2-{3-Cyano-4-[2-(4-diethylamino-2-hy-droxyphenyl)ethenyl]-5,5-dimethyl-2,5
      dihydrofuran-2-ylidene}malononitrile acetone 0.25-solvate.
AB  - In the title compound, C(22)H(22)N(4)O(2).0.25C(3)H(6)O, the disordered acetone
      mol-ecule lies with partial occupancy about the 2 axis. The mol-ecule of the
      malononitrile derivative is essentially planar excluding the methyl groups, with
      the largest deviation from the mean plane through the non-H atoms being 0.1955
      (13) A. Two rotamers with different orientations of the benzene ring are observed
      in the ratio of 0.919 (2):0.081 (2), and as a result the OH group is disordered
      over two sets of sites. In the crystal, the mol-ecules form ribbons along (101)
      utilizing a strong O-H?N(cyano) hydrogen bond. Inter-leaving of the nearly planar
      ribbons is provided by the twofold disordered acetone molecule through C-H?O
      inter-actions.

PMID- 23125766
TI  - 1,1,2,2-Tetra-kis[2,4-dichloro-6-(dieth-oxy-meth-yl)phen-oxy-meth-yl]ethene.
AB  - In the title compound, C(50)H(60)Cl(8)O(12), the mol-ecules are disordered about
      an inversion center located at the mid-point of the central C=C bond. These atoms
      show disorder and were modelled with two different orientations with site
      occupancies of 0.828 (3) and 0.172 (3). The dihedral angle between the two
      benzene rings in the asymmetric unit is 52.80 (6) degrees . Intramolecular C-H?O
      and C-H?Cl interactions occur and the crystal packing features inversion dimers
      linked by pairs of C-H?O bonds, generating R(2) (2)(10) loops.

PMID- 23125767
TI  - 6-Meth-oxyisobenzofuran-1(3H)-one.
AB  - In the title compound, C(9)H(8)O(3), the mol-ecular skeleton is almost planar
      [r.m.s. deviation = 0.016 (2) A]. Weak inter-molecular C-H?O and C-H?pi inter
      actions consolidate the crystal packing, with the mol-ecules stacking in the
      [101] direction.

PMID- 23125768
TI  - 2-Acetyl-1,1,3,3-tetra-methyl-guanidine.
AB  - In the mol-ecule of the title compound, C(7)H(15)N(3)O, the central C atom is
      surrounded in a nearly ideal trigonal-planar geometry by three N atoms. The C-N
      bond lengths in the CN(3) unit are 1.3353 (13), 1.3463 (12) and 1.3541 (13) A,
      indicating an inter-mediate character between a single and a double bond for each
      C-N bond. The bonds between the N atoms and the terminal C-methyl groups all have
      values close to that of a typical single bond [1.4526 (13)-1.4614 (14) A]. In the
      crystal, the guanidine mol-ecules are connected by weak C-H?O and C-H?N hydrogen
      bonds, generating layers parallel to the ab plane.

PMID- 23125769
TI  - rac-4-Chloro-2-[({2-[(3-chloro-6-hy-droxy-2,4-dimethyl-benz-yl)(meth-yl)amino]
      prop-yl}(meth-yl)amino)-meth-yl]-3,5-dimethyl-phenol.
AB  - The title compound, C(23)H(32)Cl(2)N(2)O(2), a potential chiral ligand for
      coordination chemistry, was prepared by a two-step reaction. The mol-ecule is
      located on a crystallographic centre of inversion. As a result, the methyl group
      bonded to the methyl-ene group is disordered over two equally occupied positions,
      sharing the same site as the H atom of the chiral C atom. As a further
      consequence of the crystallographic centrosymmetry, the 1,2-diamino-propane unit
      adopts an anti-periplanar conformation and the two benzene rings are coplanar.
      The central chain is in an all-trans arrangement. An intra-molecular O-H?N
      hydrogen bond makes an S(6) ring motif. A C-H?pi inter-action links the mol
      ecules into one-dimensional chains along the [001] direction.

PMID- 23125770
TI  - 4-Dimethyl-amino-N'-(2-hy-droxy-4-meth-oxy-benzyl-idene)benzohydrazide methanol
      monosolvate.
AB  - The asymmetric unit of the title compound, C(17)H(19)N(3)O(3).CH(4)O, comprises
      two Schiff base mol-ecules and two methanol solvent mol-ecules. The Schiff base
      mol-ecules are approximately planar, with r.m.s. deviations from the planes
      defined by the non-H atoms of 0.107 and 0.154 A, and with dihedral angles between
      the benzene rings of 4.49 (15) and 8.39 (15) degrees , respectively. This near
      planarity is assisted by the formation of intra-molecular O-H?N hydrogen bonds in
      each mol-ecule. In the crystal, the components are linked by N-H?O and O-H?O
      hydrogen bonds to form chains along [010].

PMID- 23125771
TI  - 2,4-Bis(4-eth-oxy-phen-yl)-1-methyl-3-aza-bicyclo-[3.3.1]nonan-9-one.
AB  - In the title compound, C(25)H(30)NO(3), a crystallographic mirror plane bis-ects
      the mol-ecule. Although it is a positional isomer of 2,4-bis(4-eth-oxy-phen-yl)-7
      methyl-3-aza-bicyclo-[3.3.1]non-an-9-one [C(25)H(31)NO(3), M(r) = 393.51; Park et
      al. (2012c ?). Acta Cryst. E68, o779-780], its mol-ecular weight is 392.50 due to
      the 50:50 ratio of the methyl group at bridgehead C atoms. However, the title
      compound exists in the same twin-chair conformation as its 7-methyl isomer. Also,
      the 4-eth-oxy-phenyl groups are equatorially oriented on the bicycle as in its
      isomer. In the title compound, the cyclo-hexanone ring deviates from an ideal
      chair (total puckering amplitude Q(T) = 0.5390 A) and the piperidone ring is
      closer to an ideal chair (Q(T) = 0.6064 A). These Q(T) values are very similar to
      those of its isomer. Even though a center of symmetry passes through the 7-methyl
      analog, the benzene rings are oriented 26.11 (3) degrees  with respect to each
      other, whereas the orientation is 53.10 (3) degrees  for the title compound. The
      title compound exhibits inter-molecular N-H?O inter-actions [H?A = 2.25 (2) A,
      versus 2.26 (2) A for the analog].

PMID- 23125772
TI  - N-[(3RS,4SR)-1-Benzyl-4-methyl-piperi-din-3-yl]-1-(4-methylphenyl-sulfonyl)-5
      nitro-1H-pyrrolo-[2,3-b]pyridin-4-amine.
AB  - The structure of the title compound, C(27)H(29)N(5)O(4)S, displays an intra
      molecular N-H?O hydrogen bond. The pyrrolo-[2,3-b]pyridine core makes a dihedral
      angle of 85.5 (4) degrees  with the benzyl residue and a dihedral angle of 89.4
      (9) degrees  with the tosyl ring. The nitro group is slightly twisted out of the
      plane of the planar pyrrolo-pyridine system [(-N-)C-C-N-O torsion angle = -4.61
      (18) degrees  and (-NH-)C-C-N-O = -6.46 (18) degrees ].

PMID- 23125773
TI  - (3-Oxo-3H-benzo[f]chromen-1-yl)methyl N,N-dimethyl-carbamodithio-ate.
AB  - In the title compound, C(17)H(15)NO(2)S(2), the 3H-benzo[f]chromene ring system
      is distinctly twisted; the dihedral angle between the pyran ring and its opposite
      benzene ring is 9.11 (8) degrees . The N,N-dimethyl-carbamodithio-ate residue
      lies almost perpendicular to the pyran ring [dihedral angle = 85.15 (7) degrees
      ]. In the crystal, weak C-H?O hydrogen bonds link the mol-ecules into C(10)
      chains propagating in [001].

PMID- 23125774
TI  - 4-(Naphthalene-2-carboxamido)-pyridin-1-ium thio-cyanate-N-(pyridin-4
      yl)naphthalene-2-carboxamide (1/1).
AB  - The asymmetric unit of the title compound, C(16)H(13)N(2)O(+).NCS(
      ).C(16)H(12)N(2)O, contains two N-(pyridin-4-yl)naphthalene-2-carboxamide mol
      ecules, both are partially protonated in the pyridine moiety, i.e. the H atom
      attached to the pyridine N atom is partially occupied with an occupancy factor of
      0.61 (3) and 0.39 (3), respectively. In the crystal, protonated and neutral N
      (pyridin-4-yl)naphthalene-2-carboxamide mol-ecules are linked by N-H?N hydrogen
      bonding; the thio-cyanate counter-ion links with both protonated and neutral N
      (pyridin-4-yl)naphthalene-2-carboxamide mol-ecules via N-H?S and N-H?N hydrogen
      bonding. The dihedral angles between the pyridine ring and naphthalene ring
      systems are 11.33 (6) and 9.51 (6) degrees , respectively. pi-pi stacking is
      observed in the crystal structure, the shortest centroid-centroid distance being
      3.5929 (8) A. The crystal structure was determined from a nonmerohedral twin
      {ratio of the twin components = 0.357 (1):0.643 (1) and twin law [-100 0-10 
      101]}.

PMID- 23125775
TI  - 2-Ethyl-3,5,6-triphenyl-pyrazine.
AB  - In the title mol-ecule, C(24)H(20)N(2), the pyrazine ring is significantly
      distorted from planarity, presumably due to steric crowding, and its conformation
      is well described as a flattened twist-boat. The benzene ring adjacent to the
      ethyl group forms dihedral angles of 53.79 (13) and 85.47 (12) degrees  with the
      other benzene rings; the dihedral angle between adjacent benzene rings is 57.90
      (12) degrees . The ethyl group is disordered over two positions; the site
      occupancy factor of the major component is 0.546 (4). No hydrogen bonds are found
      in the crystal structure.

PMID- 23125776
TI  - Benzyl-ammonium hexa-noate.
AB  - A binary mixture of benzyl-amine and hexa-noic acid has been reacted to form the
      title salt, C(7)H(10)N(+).C(6)H(11)O(2) (-). This crystal has a 1:1 stoichiometry
      of acid- and amine-derived species which contrasts with other related species
      which can have a number of other integer ratios of acid and amine components. The
      diffraction data indicate complete transfer of a proton from the acid to the
      amine to give the salt, comprising a cation and anion combination, with the
      formation of three hydrogen bonds around each ammonium group. This contrasts with
      other related species.

PMID- 23125777
TI  - N-{2-[2-(2-Cyano-4,6-di-nitro-phen-yl)diazen-yl]-5-(diethyl-amino)phen
      yl}acetamide.
AB  - The title compound, C(19)H(19)N(7)O(5), exhibits substitutional disorder of the
      ortho-nitro and cyano groups, with site-occupancy factors of 0.686 (7):0.314 (7).
      The two aromatic rings are essentially coplanar, with a dihedral angle of 6.6 (5)
      degrees . In the diethyl-amino group, the two ethyl groups lie on the same side
      of the amino-benzene plane. An intra-molecular N-H?N hydrogen bond links the
      amino and diazenyl groups.

PMID- 23125778
TI  - 2-(Furan-2-yl)-1,3-bis(furan-2-ylmeth-yl)-1H-benzimidazol-3-ium chloride
      monohydrate.
AB  - The title hydrated salt, C(21)H(17)N(2)O(3) (+).Cl(-).H(2)O, exhibits disorder in
      one of the furan rings. The major and minor components have a refined occupancy
      ratio of 0.844 (19):0.156 (19). The structure displays intermolecular hydrogen
      bonding involving the water molecule and the chloride anion. Close intermolecular
      C-H?Cl and C-H?(furan ring) inter-actions complete the hydrogen bonding.

PMID- 23125779
TI  - 3-Chloro-methyl-6,7-dimethyl-1,2-benz-oxazole.
AB  - In the title compound, C(10)H(10)ClNO, the benzoisoxazole ring is almost planar
      (r.m.s. deviation = 0.0121 A) and the chloro substituent in the side chain is
      anti-clinal relative to the N-C bond of the isoxazole ring. In the crystal,
      adjacent mol-ecules are linked via a pair of weak C-H?N hydrogen bonds, forming
      dimers through a cyclic R(2) (2)(8) association.

PMID- 23125780
TI  - N,N'-Dibenzyl-N''-(2-chloro-2,2-difluoro-acet-yl)phospho-ric triamide.
AB  - In the title mol-ecule, C(16)H(17)ClF(2)N(3)O(2)P, the N-H unit of the
      C(=O)NHP(=O) fragment adopts a syn orientation with respect to the P=O group. The
      two F atoms and the Cl atom of the ClF(2)C group are disordered over two sets of
      sites with refined occupancies of 0.605 (6) and 0.395 (6). In the crystal, mol
      ecules are linked via N-H?O=C hydrogen bonds the and the (N-H?)(N-H?)O=P group
      into chains along [010].

PMID- 23125781
TI  - Ethyl 2-(3,4-dimethyl-5,5-dioxo-1H,4H-benzo[e]pyrazolo-[4,3-c][1,2]thia-zin-1
      yl)acetate.
AB  - In the title mol-ecule, C(15)H(17)N(3)O(4)S, the heterocyclic thia-zine ring
      adopts a twist-boat conformation, which differs from that in related compounds,
      with adjacent S and C atoms displaced by 0.981 (4) and 0.413 (5) A, respectively,
      on the same side of the mean plane formed by the remaining ring atoms. The mean
      plane of the benzene ring makes a dihedral angle of 23.43 (14) degrees  with the
      mean plane of the pyrazole ring. In the crystal, mol-ecules are connected by weak
      C-H?O hydrogen bonds to form a three-dimensional network. The H atoms of the
      methyl group attached to the pyrazole ring were refined over six sites with equal
      occupancies.

PMID- 23125782
TI  - 4-Diphenyl-phosphanyl-1,5-naphthyridine.
AB  - The asymmetric unit of the title compound, C(20)H(15)N(2)P, contains two
      independent mol-ecules with similar structures. The 1,5-naphthyridine ring system
      is nearly planar, with maximum deviations of 0.010 (3) and 0.012 (3) A; its mean
      plane is oriented with respect to the two phenyl rings at 79.69 (12) and 84.00
      (10) degrees  in one mol-ecule, and at 74.25 (12) and 82.05 (11) degrees  in the
      other. The two phenyl rings are twisted with respect to each other with a
      dihedral angle of 75.96 (14) degrees  in one mol-ecule and 86.30 (13) degrees  in
      the other.

PMID- 23125783
TI  - (2-Benzoyl-phen-yl)(naphthalen-1-yl)methanone.
AB  - In the title compound, C(24)H(16)O(2), the naphthalene ring system makes dihedral
      angles of 78.5 (6) and 65.5 (7) degrees  with the terminal and central benzene
      rings, respectively. The dihedral angle between the benzene rings is 74.5 (8)
      degrees . In the crystal, neighbouring molecules are interlinked through two C
      H?pi interactions, which construct a two-dimensional supramolecular framework
      extending infinitely along (010).

PMID- 23125784
TI  - N-(2,3-Dimethyl-phen-yl)-4-methyl-N-(4-methyl-phenyl-sulfon-yl)benzene
      sulfonamide.
AB  - In the title compound, C(22)H(23)NO(4)S(2), the dihedral angles between the
      dimethyl-phenyl ring and the two methyl-phenyl rings are 41.19 (15) and 20.50
      (17) degrees ; the dihedral angle between the methyl-phenyl rings is 48.11 (14)
      degrees . The C-N-S-C torsion angles are -87.6 (2) and 77.43 (18) degrees . The
      only possible directional inter-actions in the crystal are very weak C-H?pi inter
      actions and very weak pi-pi stacking between parallel methyl-phenyl rings
      [centroid-to-centroid separation = 4.010 (2) A and slippage = 1.987 A].

PMID- 23125785
TI  - Tetra-methyl-ammonium hydrogen terephthalate.
AB  - The asymmetric unit of the title salt, C(4)H(12)N(+).C(8)H(5)O(4) (-), contains
      one half of a tetra-methyl-ammonium cation and one half of a hydrogen
      terephthalate monoanion. The N atom of the ammonium cation lies on a twofold
      rotation axis and the centre of mass of the terephthalate anion is on a centre of
      inversion. In the crystal, the centrosymmetric terephthalate ions are linked by a
      very short symmetric O-H?O hydrogen bond [O?O = 2.4610 (19) A] into a one
      dimensional polymeric chain along [1-12]. The tetra-methyl-ammonium cations and
      terephthalate anions are then connected through a pair of bifurcated acceptor C
      H?O hydrogen bonds, generating a three-dimensional supra-molecular network. The
      carboxyl-ate groups at both ends of the terephthalate anion are charge-shared
      with an equal probability of 0.5.

PMID- 23125786
TI  - 6-Bromo-1,3-benzothia-zol-2-amine.
AB  - The r.m.s. deviation from the mean plane for the non-H atoms in the title
      compound, C(7)H(5)BrN(2)S, is 0.011 A. In the crystal, the mol-ecules are linked
      by N-H?N and N-H?Br hydrogen bonds to generate (010) sheets. Weak aromatic pi-pi
      stacking [centroid-to-centroid separation = 3.884 (10) A] and possible C-H?Br
      inter-actions are also observed. The crystal studied was found to be an inversion
      twin.

PMID- 23125787
TI  - Ethyl 4-{[1-(2,4-dichloro-benz-yl)-1H-1,2,3-triazol-4-yl]meth-oxy}-8-(trifluoro
      meth-yl)quinoline-3-carboxyl-ate.
AB  - In the title compound, C(23)H(17)Cl(2)F(3)N(4)O(3), the triazole ring makes
      dihedral angles of 50.27 (6) and 82.78 (7) degrees  with the quinoline ring
      system and the dichloro-substituted benzene ring. The dihedral angle between the
      quinoline and dichloro-substituted benzene rings is 38.17 (4) degrees . In the
      crystal, mol-ecules are linked via C-H?N, C-H?F and C-H?O hydrogen bonds into a
      three-dimensional network. The crystal is further consolidated by C-H?pi contacts
      to the triazole ring and inversion-related pi-pi inter-actions between the
      benzene and pyridine rings of quinoline systems [centroid-centroid distance =
      3.7037 (7) A].

PMID- 23125788
TI  - 4,4'-[(2R*,3R*,4R*,5R*)-3,4-Dimethyl-tetra-hydro-furan-2,5-di-yl]diphenol.
AB  - The title mol-ecule, C(18)H(20)O(3), is a furan-oid lignan extracted from the
      leaves of Larrea tridentata. The relative absolute configuration for the four
      chiral centers was established, showing that this compound is 4-epi-larreatricin,
      which has been previously reported in the literature. The mol-ecule displays
      noncrystallographic C(2) symmetry, with the methyl and phenol substituents
      alternating above and below the mean plane of the furan ring. The conformation of
      this ring is described by the pseudorotation phase angle P = 171.3 degrees  and
      the maximum out-of-plane pucker nu(m) = 37.7 degrees . These parameters indicate
      that the furan ring adopts the same conformation as the ribose residues in B-DNA.
      The packing is dominated by inter-molecular O-H?O hydrogen bonds. The phenol hy
      droxy groups form chains in the [110] direction and these chains inter-act via O
      H?O(furan) contacts.

PMID- 23125789
TI  - Propan-2-yl r-4-(4-fluoro-phen-yl)-3-hy-droxy-c-6-methyl-2-phenyl-4,5-dihydro-2H
      indazole-t-5-carboxyl-ate.
AB  - In the title compound, C(24)H(23)FN(2)O(3), the cyclo-hexene ring adopts a screw
      boat conformation. The fluorobenzene ring attached to the cyclo-hexene ring and
      the phenyl ring attached to the indazole moiety are inclined to one another by
      57.77 (13) degrees . In the crystal, mol-ecules are linked by O-H?N and C-H?O
      hydrogen bonds, forming chains with C(5) and C(10) graph-set motifs. There are
      also C-H?pi inter-actions present. The isopropoxycarbonyl group undergoes
      considerable thermal motion.

PMID- 23125790
TI  - tert-Butyl N-{4-[N-(4-hy-droxy-phen-yl)carbamo-yl]benz-yl}carbamate.
AB  - In the title compound, C(19)H(22)N(2)O(4), the dihedral angle between the
      aromatic rings is 67.33 (2) degrees . In the crystal, mol-ecules are linked
      through N-H?O and O-H?O hydrogen bonds, generating a two-dimensional network
      lying parallel to (100). As a result of the twist of the mol-ecular skeleton and
      the hindrance of the tert-butyl groups, no pi-pi inter-actions exist between the
      aromatic rings.

PMID- 23125791
TI  - Methyl 2-oxo-2H-chromene-3-carboxyl-ate.
AB  - The title compound, C(11)H(8)O(4), features an almost planar mol-ecule (r.m.s.
      deviation = 0.033 A for all non-H atoms). In the crystal, the mol-ecules are
      linked via C-H?O hydrogen bonds, forming two-dimensional networks lying parallel
      to (1-21).

PMID- 23125792
TI  - 2-Amino-4-methyl-4,5,6,7-tetrahydro-1-benzothiophene-3-carbonitrile.
AB  - In the title compound, C(10)H(12)N(2)S, the thio-phene ring is essentially planar
      (r.m.s. deviation = 0.0290 A). The two C atoms of the cyclo-hexene ring (at
      positions 6 and 7) are disordered over two sets of sites in a 0.810 (5):0.190 (5)
      ratio. The cyclo-hexene rings in both the major and minor occupancy conformers
      adopt a half-chair conformation. In the crystal, there are two types of N-H?N
      inter-action. One of these results in centrosymmetric head-to-head dimers
      corresponding to an R(2) (2)(12) graph-set motif and the other forms a 20
      membered macrocyclic ring involving six mol-ecules.

PMID- 23125793
TI  - 4-Meth-oxy-N-[(E)-(5-nitro-thio-phen-2-yl)methyl-idene]aniline.
AB  - The title mol-ecule, C(12)H(10)N(2)O(3)S, is nonplanar with an inter-planar angle
      of 33.44 (7) degrees  between the benzene and thio-phene rings. In the crystal
      there exist only weak inter-molecular C-H?O inter-actions, pi-pi inter-actions
      between the benzene rings [centroid-centroid distance = 3.7465 (14) A] and X-Y?pi
      inter-actions to the thio-phene and benzene rings [N?centroid distances = 3.718
      (3) and 3.355 (3) A, respectively]. Inter-molecular C-H?O inter-actions link the
      mol-ecules into chains parallel to the a axis.

PMID- 23125794
TI  - (E)-1-[(3-Iodo-phen-yl)imino-meth-yl]naphthalen-2-ol.
AB  - In the title mol-ecule, C(17)H(12)INO, the dihedral angle between the
      naphthaldeyde plane and the 3-iodo-aniline plane is20.07 (13) degrees . It exists
      in the solid state as an enol-imine tautomer with a strong intra-molecular O-H?N
      hydrogen bond.

PMID- 23125795
TI  - 4-Meth-oxy-N-(4-meth-oxy-2-nitro-phen-yl)benzamide.
AB  - In the title compound, C(15)H(14)N(2)O(5), the central amide C-C(=O)-N-C unit
      forms dihedral angles of 28.17 (13) and 26.47 (13) degrees  with the two benzene
      rings, whereas the two benzene rings are almost coplanar, making a dihedral angle
      of 4.52 (13) degrees . The two meth-oxy and the nitro substituents are almost
      coplanar with their attached benzene rings, with C-O-C-C torsion angles of -1.3
      (4) and -4.6 (4) degrees , and an O-N-C-C torsion angle of 17.1 (3) degrees . In
      the crystal, mol-ecules are linked via C-H?O and N-H?O inter-actions, forming a
      tape running along the b axis.

PMID- 23125796
TI  - 4-(Cyclo-propane-carboxamido)-benzoic acid.
AB  - In the title compound, C(11)H(11)NO(3), the dihedral angle between the benzene
      ring and the cyclo-propane ring is 63.2 (1) degrees . In the crystal, mol-ecules
      are linked through classical cyclic carb-oxy-lic acid O-H?O hydrogen-bond inter
      actions [graph set R(2) (2)(8)] giving centrosymmetric dimers which are extended
      along the b-axis direction through amide N-H?O hydrogen-bond inter-actions,
      giving one-dimensional ribbon structures. Weak C-H?O inter-actions are also
      present in the structure.

PMID- 23125797
TI  - (E)-N-(3,3-Diphenyl-allyl-idene)-3-nitro-aniline.
AB  - In the title compound, C(21)H(16)N(2)O(2), the 3-nitro-phenyl and two phenyl
      rings are twisted from the mean plane of the enimino fragment by 44.4 (1), 37.2
      (1) and 74.1 (1) degrees , respectively. The crystal packing exhibits no
      classical inter-molecular contacts.

PMID- 23125798
TI  - (E)-N-(3,3-Diphenyl-allyl-idene)-4-nitro-aniline.
AB  - In the title compound, C(21)H(16)N(2)O(2), the dihedral angles between the mean
      planes of the 4-nitro-phenyl ring and the two phenyl rings are 57.3 (5) and 16.8
      (6) degrees . The imine group displays a C-C-N-C torsion angle of -24.9 (3)
      degrees .

PMID- 23125799
TI  - Ethyl 2,4-dimethyl-pyrido[1,2-a]benz-imidazole-3-carboxyl-ate.
AB  - The title compound, C(16)H(16)N(2)O(2), was synthesized using a novel tandem
      annulation reaction between 1-(1H-benzo[d]imidazol-2-yl)ethanone and ethyl (E)-4
      bromo-but-2-enoate under mild conditions. The dihedral angles formed by the mean
      plane of the five-membered imidazole ring with the dihydro-pyridin and benzene
      rings are 1.54 (9) and 1.85 (9) degrees , respectively.

PMID- 23125800
TI  - Redetermination of 2,2'-bipyridine-1,1'-diium dibromide.
AB  - In the title mol-ecular salt, C(10)H(10)N(2) (2+).2Br(-), the dihedral angle
      between the aromatic rings is 20.83 (14) degrees  and the N-H groups have a
      transoid conformaton [N-C-C-N = 158.5 (3) degrees ]. In the crystal, the cations
      are linked to the anions by two N-H?Br and five C-H?Br hydrogen bonds, generating
      corrugated sheets incorporating R(2) (1)(7), R(4) (2)(10), R(4) (2)(11) and two
      different R(4) (2)(12) loops. This structure was originally reported by Nakatsu
      et al. [Acta Cryst (1972), A28, S24], but no atomic coordinates are available.

PMID- 23125801
TI  - (8aR,9R)-9-Hy-droxy-7,8,8a,9-tetra-hydro-furo[3,2-f]indolizin-6(4H)-one.
AB  - The title compound, C(10)H(11)NO(3), crystallizes with four independent mol
      ecules in the asymmetric unit. Their geometries are very similar and
      corresponding bond distances are almost identical. The central six-membered ring
      of the indolizine moiety adopts a envelope conformation [the displacement of the
      flap atom (the C atom opposite the N atom) being 0.539 (2), 0.548 (3), 0.509 (3)
      and 0.544 (3) A in the four molecules], while the conformation of the
      oxopyrrolidine ring is close to that of a flat envelope. The displacements of the
      non-fused C atom opposite the C=O group of the pyrrolidine ring of the four mol
      ecules are 0.366 (3), 0.335 (3), 0.173 (3) and -0.310 (3) A. In the crystal, O
      H?O hydrogen bonds link the mol-ecules into chains, which run parallel to the c
      axis. The absolute configuration was assigned from the synthesis.

PMID- 23125802
TI  - (Z)-3-Methyl-1-phenyl-4-[(p-tol-yl)(p-tolyl-amino)-methyl-idene]-1H-pyrazol-5(4H)
      one.
AB  - In the title mol-ecule, C(25)H(23)N(3)O(2), the pyrazole ring forms dihedral
      angles of 28.56 (7), 80.35 (7) and 31.99 (7) degrees  with the phenyl ring, the p
      tolyl ring and the p-tolyl-amino ring, respectively. The N-H group attached to
      the exocyclic C=C bond is in a syn arrangement with respect to the C=O bond of
      the pyrazolone group and an intra-molecular N-H?O hydrogen bond is observed. In
      the crystal, weak C-H?pi inter-actions link mol-ecules along [100].

PMID- 23125803
TI  - 6-Hy-droxy-imino-5alpha-cholestane.
AB  - The title compound, C(27)H(47)NO, is a steroid derivative composed of a saturated
      carbon fused-ring framework with an alkyl side chain. Ring bond lengths have
      normal values with an average of 1.533 (2) A, while the cholestane side chain
      shows an average bond length of 1.533 (2) A. The three cyclohexane rings adopt
      chair conformations or close to chair conformations while the cyclopentane ring
      is twisted. The cholesterol side-chain is fully extended with a gauche-trans
      conformation of the terminal methyl groups. There are eight chiral centres in the
      molecule; the absolute configuration of these sites was determined from the
      structure presented. There are two molecules in the asymmetric unit; in one, the
      alkyl chain is disordered over two sets of sites [occupancy ratios of 0.50:0.50
      and 0.67:0.33].

PMID- 23125804
TI  - 1-Benzyl-piperidin-4-one O-(2-bromo-benz-yl)oxime.
AB  - In the title mol-ecule, C(19)H(21)BrN(2)O, the piperidone ring adopts a chair
      conformation with a total puckering amplitude Q(T) of 0.554 (2) A. The dihedral
      angle between the benzene rings is 64.10 (7) degrees . There are no significant
      inter-molecular inter-actions.

PMID- 23125805
TI  - 12-(4-Meth-oxy-benzo-yl)-2-methyl-benzo[f]pyrido[1,2-a]indole-6,11-dione.
AB  - In the title compound, C(25)H(17)NO(4), the indolizine fused naphthaquinone unit
      is approximately planar [r.m.s deviation = 0.0678 A] and makes a dihedral angle
      of 57.82 (5) degrees  with the benzene ring of the meth-oxy-benzene group. The
      naphtho-quinone O atoms deviate, in the same sense, from the mean plane of the
      fused six-membered rings by 0.2001 (14) and 0.0516 (14) A. In the crystal there
      is pi-pi stacking of inversion-related pairs of mol-ecules [inter-planar spacing
      = 3.514 (2) A].

PMID- 23125806
TI  - (2S,7S)-10-Ethyl-1,8,10,12-tetra-aza-tetra-cyclo-[8.3.1.1(8,12).0(2,7)]penta
      decan-10-ium iodide.
AB  - The title chiral quaternary ammonium salt, C(13)H(25)N(4) (+).I(-), was
      synthesized through the Menschutkin reaction between the cage aminal (2S,7S)
      1,8,10,12-tetra-aza-tetra-cyclo-[8.3.1.1(8,12).0(2,7)]penta-decane and ethyl
      iodide. The quaternization occurred regioselectively on the nitrogen with major
      sp3 character. The crystal structure consists of anions and cations separated by
      normal distances. Ions are not linked through C-H?I hydrogen bonds.

PMID- 23125807
TI  - 4,4'-Difluoro-2,2'-[imidazolidine-1,3-diylbis(methyl-ene)]diphenol.
AB  - In the title compound, C(17)H(18)F(2)N(2)O(2), the imidazolidine ring system
      exists in a twist conformation. The mean plane through this ring system forms
      dihedral angles of 80.8 (8) degrees  and 66.2 (13) degrees , with the benzene
      rings. The dihedral angle between the benzene rings is 52.0 (14) degrees . Two
      intra-molecular O-H?N hydrogen bonds each generate S(6) ring motifs. In the
      crystal, weak C-H?O hydrogen bonds form dimers, which are connected by further C
      H?O inter-actions.

PMID- 23125808
TI  - 3-Methyl-5-methyl-sulfanyl-1,3,4-thia-diazole-2(3H)-thione.
AB  - The title compound, C(4)H(6)N(2)S(3), has two very similar mol-ecules per
      asymmetric unit. The nine non-H atoms in each mol-ecule are coplanar, both having
      comparable r.m.s. deviations of 0.002 A. The main inter-est in the rather simple
      structure resides in a survey of very weak (in some cases, borderline) non
      bonding inter-actions of various kinds, viz. S?S, C-H?pi, pi-pi [centroid
      centroid distance = 3.8958 (13) A] and C-S?pi [3.7271 (11) A], which act as the
      major driving force for the arrangement of mol-ecules in the structure. The role
      of long, though highly directional, S?S contacts (d > 3.60 A), and their
      relevance to the stability of the structure is discussed.

PMID- 23125809
TI  - 7-Bromo-1-(3-fluoro-phenyl-sulfon-yl)-2-methyl-naphtho-[2,1-b]furan.
AB  - In the title compound, C(19)H(12)BrFO(3)S, the 3-fluoro-phenyl ring makes a
      dihedral angle of 80.85 (5) degrees  with the mean plane [r.m.s. deviation =
      0.009 (2)A] of the naphtho-furan fragment. In the crystal, mol-ecules are linked
      by slipped pi-pi inter-actions between the furan and the outer benzene rings of
      neighbouring mol-ecules [centroid-centroid distance = 3.756 (3) A and slippage of
      1.189 (3) A].

PMID- 23125810
TI  - 1-(5-Hy-droxy-2,2,8,8-tetra-methyl-2H,8H-pyrano[2,3-f]chromen-6-yl)ethanone.
AB  - In the title compound, C(18)H(20)O(4),the pyran ring of the chromene unit adopts
      a half-chair conformation. An intra-molecular O-H?O hydrogen bond occurs. In the
      crystal, mol-ecules are linked along the b axis by C-H?O hydrogen bonds.

PMID- 23125811
TI  - 2-Acetyl-phenyl (2E)-3-(4-fluoro-phen-yl)acrylate.
AB  - In the title compound, C(17)H(13)FO(3), the dihedral angle between the benzene
      rings is 70.34 (5) degrees . In the crystal, molecules are linked via pairs of
      bifurcated C-H?(O,O) hydrogen bonds, forming inversion dimers. These dimers are
      linked via C-H?O and C-H?F inter-actions, forming a three-dimensional structure.

PMID- 23125812
TI  - 4,4'-Diethyl-2,2'-[(N-cyclo-hexyl-imino)-bis-(methyl-ene)]diphenol.
AB  - The title compound, C(24)H(33)NO(2), exhibits an intra-molecular hydrogen bond
      between a phenol -OH group and the N atom. In the crystal, mol-ecules are
      connected by pairs of O-H?O hydrogen bonds.

PMID- 23125813
TI  - N-[(3RS,4RS)-1-Benzyl-4-methyl-piperidin-3-yl]-5-nitro-1-phenyl-sulfonyl-1H
      pyrrolo-[2,3-b]pyridine-4-amine.
AB  - The pyrrolo-pyridine system in the title compound, C(27)H(29)N(5)O(4)S, is
      oriented at a dihedral angle of 71.20 (5) degrees  towards the phenyl ring of the
      tosyl residue and at a dihedral angle of 45.43 (4) degrees  towards the benzyl
      group. The structure shows an intra-molecular N-H?O and a weak intra-molecular N
      H?N hydrogen bond. The piperidine ring adopts a chair conformation, with the cis
      substituents displaying a torsion angle of -54.59 (18) degrees .

PMID- 23125814
TI  - 1-[(3RS,4RS)-1-Benzyl-4-methyl-piperi-din-3-yl]-1,6-dihydro-imidazo[4,5-d]pyrrolo
      [2,3-b]pyridine hemihydrate.
AB  - The benzyl residue in the title compound, C(21)H(23)N(5).0.5H(2)O, is oriented at
      a dihedral angle of 83.8 (3) degrees  towards the 1,6-dihydro-imidazo[4,5
      d]pyrrolo-[2,3-b]pyridine system. The piperidine ring adopts a chair conformation
      with the cis substituents displaying a torsion angle of -45.91 (16) degrees . In
      the crystal, mol-ecules are accumulated as racemic dimers by two inter-molecular
      hydrogen bonds between the pyrrolo-pyridine systems. Another hydrogen bond is
      formed between the imidazole ring and the cocrystallized water mol-ecule, which
      is located on a twofold rotation axis.

PMID- 23125815
TI  - 3-[1-(3-Hy-droxy-benz-yl)-1H-benzimid-azol-2-yl]phenol dimethyl sulfoxide
      monosolvate.
AB  - Crystals of the title compound were obtained as a 1:1 dimethyl sulfoxide solvate,
      C(20)H(16)N(2)O(2).C(2)H(6)O. The mol-ecular conformation of the organic mol
      ecule is similar to that in the previously reported unsolvated structure [Eltayeb
      et al. (2009 ?). Acta Cryst. E65, o1374-o1375]. Thus, the dihedral angles formed
      by the benzimidazole moiety with the two benzene rings are 57.54 (4) and 76.22
      (5) degrees , and the dihedral angle between the benzene rings is 89.23 (5)
      degrees . In the crystal, a three-dimensional network features O-H?O, O-H?N and O
      H?S hydrogen bonds, as well as C-H?O and C-H?pi inter-actions.

PMID- 23125816
TI  - (2E)-2-{[3-Methyl-5-(2-naphth-yloxy)-1-phenyl-1H-pyrazol-4-yl]methyl
      idene}hydrazinecarbothio-amide monohydrate.
AB  - In the title compound, C(22)H(19)N(5)OS.H(2)O, the naphthalene ring system and
      the benzene ring [dihedral angle = 85.19 (8) degrees ] make dihedral angles of
      87.02 (9) and 14.41 (10) degrees , respectively, with the pyrazole ring. The mean
      plane through the 2-methyl-enehydrazinecarbothio-amide group [C-N-N-C(=S)-N;
      maximum deviation = 0.022 (1) A] is slightly twisted from the pyrazole ring
      [dihedral angle = 5.60 (11) degrees ]. In the crystal, mol-ecules are linked by N
      H?S, N-H?O, O-H?S, O-H?N and C-H?S hydrogen bonds into sheets parallel to the ab
      plane. pi-pi inter-actions are also observed [centroid-to-centroid distances =
      3.7778 (12) and 3.7010 (12) A].

PMID- 23125817
TI  - 5-Chloro-2-(3,4,5-trimeth-oxy-phen-yl)-1,3-benzothia-zole.
AB  - In the title compound, C(16)H(14)ClNO(3)S, the dihedral angle between the almost
      planar benzothia-zole ring system [maximum deviation = 0.012 (3) A] and the
      aromatic ring of the trimeth-oxy-phenyl group is 15.56 (6) degrees . In the
      crystal, the mol-ecules are arranged into layers parallel to the bc plane, held
      together only by weak van der Waals forces.

PMID- 23125818
TI  - 5-Phenyl-1,3,4-oxadiazol-2-amine.
AB  - In the title complex, C(8)H(7)N(3)O, the C-O [1.369 (2) and 1.364 (3) A] and C=N
      [1.285 (3) and 1.289 (3) A] bond lengths in the oxadiazole ring are each almost
      identical within systematic errors, although different substituents are attached
      to the ring. The phenyl ring is inclined to the planar oxadiazole ring [r.m.s.
      deviation 0.002 A] by 13.42 (18) degrees . In the crystal, molecules are linked
      via N-H?N hydrogen bonds, forming double-stranded chains propagating along [010].

PMID- 23125819
TI  - 4-Nitro-anilinium p-toluene-sulfonate.
AB  - In the cation of the title salt, C(6)H(7)N(2)O(2) (+).C(7)H(7)O(3)S(-), the
      benzene ring makes a dihedral angle of 10.2 (2) degrees  with the nitro group. In
      the crystal, the cations and anions are linked by weak N-H?O hydrogen bonds,
      forming a layer parallel to the ac plane. A weak C-H?O inter-action and pi-pi
      inter-actions [centroid-centroid distances of 3.738 (3) and 3.748 (3) A] also
      observed within the layer.

PMID- 23125820
TI  - The relationship between older adults' self-management abilities, well-being and
      depression.
AB  - This study aimed to identify the relationship between self-management abilities,
      well-being and depression. Our study was conducted among older adults (>65 years
      of age) who were vulnerable to loss of function after hospital discharge. Three
      months after hospital admission, 296/456 patients (65 % response rate) were
      interviewed in their homes. The 30-item Self-Management Ability Scale was used to
      measure six self-management abilities: taking initiative, investing in resources
      for long-term benefits, taking care of a variety of resources, taking care of
      resource multifunctionality, being self-efficacious and having a positive frame
      of mind. Well-being was measured with the Social Production Function (SPF)
      Instrument for the Level of Well-being (SPF-IL) and Cantril's ladder. The
      Geriatric Depression Scale was used to assess depression. Correlation analyses
      showed that all self-management abilities were strong indicators for well-being
      (p < 0.001 for all). Regression analyses revealed that investing in resources for
      long-term benefits, taking care of a variety of resources, taking care of
      resource multifunctionality and being self-efficacious were associated with well
      being. While no significant relationship was found between well-being and having
      a positive frame of mind or taking initiative, regression analyses revealed that
      these self-management abilities were related to depression. Investing in
      resources for long-term benefits and taking care of a variety of resources were
      significantly related to depression. This research showed that self-management
      abilities are related to well-being and depression among older adults. In
      addition, this study identified key self-management abilities for older adults
      who had recently been discharged from a hospital.

PMID- 23125821
TI  - Movements that are both variable and optimal.
AB  - This brief review addresses two major aspects of the neural control of multi
      element systems. First, the principle of abundance suggests that the central
      nervous system unites elements into synergies (co-variation of elemental
      variables across trials quantified within the framework of the uncontrolled
      manifold hypothesis) that stabilize important performance variables. Second, a
      novel method, analytical inverse optimization, has been introduced to compute
      cost functions that define averaged across trials involvement of individual
      elements over a range of values of task-specific performance variables. The two
      aspects reflect two features of motor coordination: (1) using variable solutions
      that allow performing secondary tasks and stabilizing performance variables; and
      (2) selecting combinations of elemental variables that follow an optimization
      principle. We suggest that the conflict between the two approaches (a single
      solution vs. families of solutions) is apparent, not real. Natural motor
      variability may be due to using the same cost function across slightly different
      initial states; on the other hand, there may be variability in the cost function
      itself leading to variable solutions that are all optimal with respect to
      slightly different cost functions. The analysis of motor synergies has revealed
      specific changes associated with atypical development, healthy aging,
      neurological disorders, and practice. These have allowed formulating hypotheses
      on the neurophysiological mechanisms involved in the synergic control of actions.

PMID- 23125822
TI  - Acute stress influences neural circuits of reward processing.
AB  - People often make decisions under aversive conditions such as acute stress. Yet,
      less is known about the process in which acute stress can influence decision
      making. A growing body of research has established that reward-related
      information associated with the outcomes of decisions exerts a powerful influence
      over the choices people make and that an extensive network of brain regions,
      prominently featuring the striatum, is involved in the processing of this reward
      related information. Thus, an important step in research on the nature of acute
      stress' influence over decision-making is to examine how it may modulate
      responses to rewards and punishments within reward processing neural circuitry.
      In the current experiment, we employed a simple reward processing paradigm -
      where participants received monetary rewards and punishments - known to evoke
      robust striatal responses. Immediately prior to performing each of two task runs,
      participants were exposed to acute stress (i.e., cold pressor) or a no stress
      control procedure in a between-subjects fashion. No stress group participants
      exhibited a pattern of activity within the dorsal striatum and orbitofrontal
      cortex (OFC) consistent with past research on outcome processing - specifically,
      differential responses for monetary rewards over punishments. In contrast, acute
      stress group participants' dorsal striatum and OFC demonstrated decreased
      sensitivity to monetary outcomes and a lack of differential activity. These
      findings provide insight into how neural circuits may process rewards and
      punishments associated with simple decisions under acutely stressful conditions.

PMID- 23125824
TI  - An updated update to personality and error monitoring.

PMID- 23125823
TI  - Age-related changes in synaptic markers and monocyte subsets link the cognitive
      decline of APP(Swe)/PS1 mice.
AB  - Alzheimer's disease (AD) is characterized by a progressive memory decline and
      numerous pathological abnormalities, including amyloid beta (Abeta) accumulation
      in the brain and synaptic dysfunction. Here we wanted to study whether these
      brain changes were associated with alteration in the population of monocyte
      subsets since accumulating evidence supports the concept that the innate immune
      system plays a role in the etiology of this disease. We then determined the
      immune profile together with expression of genes encoding synaptic proteins and
      neurotrophins in APP(Swe)/PS1 mice and their age-matched wild-type (WT)
      littermates. We found that the progressive cognitive decline and the dramatic
      decrease in the expression of numerous synaptic markers and neurotrophins
      correlated with a major defect in the subset of circulating inflammatory
      monocytes. Indeed the number of CX(3)CR1(low)Ly6-C(high)CCR2(+)Gr1(+) monocytes
      remained essentially similar between 5 weeks and 6 months of age in APP(Swe)/PS1
      mice, while these cells significantly increased in 6-month-old WT littermates. Of
      great interest is that the onset of cognitive decline was closely associated with
      the accumulation of soluble Abeta, disruption of synaptic activity, alteration in
      the BDNF system, and a defective production in the subset of CX(3)CR1(low)Ly6
      C(high)CCR2(+)Gr1(+) monocytes. However, these memory impairments can be
      prevented or restored by boosting the monocytic production, using a short
      treatment of macrophage colony-stimulating factor (M-CSF). In conclusion, low
      CCR2(+) monocyte production by the hematopoietic system may be a direct biomarker
      of the cognitive decline in a context of AD.

PMID- 23125825
TI  - The cognitive chronometric architecture of reading aloud: semantic and lexical
      effects on naming onset and duration.
AB  - We examined onset reaction time (RT) in a word naming task using an additive
      factors method (AFM). The pattern of additive and over-additive joint effects on
      RT among Instructions (INST: name all, name words), Word Frequency (WF: log(10)
      HAL), Semantic Neighborhood Density (SND: Inverse Ncount), and Word Type (WT:
      regular, exception) supported a cognitive chronometric architecture consisting of
      at least two cascaded stages of processing, with the orthographic lexical system
      as the locus of the INST * WF and the INST * SND interactions, and the
      phonological output system as the locus of the WF * WT and the SND * WT
      interactions. Additivity between INST and WT supports the notion that these
      variables affect separable systems, and a WF * SND interaction supports a common
      locus of their effects. These results support stage-like/cascaded processing
      models over parallel processing models of basic reading. We also examined
      response duration (RD) in these data by recording and hand-marking vocal
      responses, which provides evidence that basic reading processes are ongoing even
      after the initiation of a vocal response, and supports the notion that the more
      lexically a word is read, the shorter the RD. As such, the effects of WT and INST
      on RD were opposite to their effects on RT however the effects of WF and SND on
      RD were in the same direction as their effects on RT. Given the combination of
      consistent and dissociating effects between RT and RD, these results provide new
      challenges to all models of basic reading processes.

PMID- 23125826
TI  - Structural correlates of skilled performance on a motor sequence task.
AB  - The brain regions functionally engaged in motor sequence performance are well
      established, but the structural characteristics of these regions and the fiber
      pathways involved have been less well studied. In addition, relatively few
      studies have combined multiple magnetic resonance imaging (MRI) and behavioral
      performance measures in the same sample. Therefore, the current study used
      diffusion tensor imaging (DTI), probabilistic tractography, and voxel-based
      morphometry (VBM) to determine the structural correlates of skilled motor
      performance. Further, we compared these findings with fMRI results in the same
      sample. We correlated final performance and rate of improvement measures on a
      temporal motor sequence task (TMST) with skeletonized fractional anisotropy (FA)
      and whole brain gray matter (GM) volume. Final synchronization performance was
      negatively correlated with FA in white matter (WM) underlying bilateral
      sensorimotor cortex-an effect that was mediated by a positive correlation with
      radial diffusivity. Multi-fiber tractography indicated that this region contained
      crossing fibers from the corticospinal tract (CST) and superior longitudinal
      fasciculus (SLF). The identified SLF pathway linked parietal and auditory
      cortical regions that have been shown to be functionally engaged in this task.
      Thus, we hypothesize that enhanced synchronization performance on this task may
      be related to greater fiber integrity of the SLF. Rate of improvement on
      synchronization was positively correlated with GM volume in cerebellar lobules
      HVI and V-regions that showed training-related decreases in activity in the same
      sample. Taken together, our results link individual differences in brain
      structure and function to motor sequence performance on the same task. Further,
      our study illustrates the utility of using multiple MR measures and analysis
      techniques to specify the interpretation of structural findings.

PMID- 23125827
TI  - A sensorimotor paradigm for Bayesian model selection.
AB  - Sensorimotor control is thought to rely on predictive internal models in order to
      cope efficiently with uncertain environments. Recently, it has been shown that
      humans not only learn different internal models for different tasks, but that
      they also extract common structure between tasks. This raises the question of how
      the motor system selects between different structures or models, when each model
      can be associated with a range of different task-specific parameters. Here we
      design a sensorimotor task that requires subjects to compensate visuomotor shifts
      in a three-dimensional virtual reality setup, where one of the dimensions can be
      mapped to a model variable and the other dimension to the parameter variable. By
      introducing probe trials that are neutral in the parameter dimension, we can
      directly test for model selection. We found that model selection procedures based
      on Bayesian statistics provided a better explanation for subjects' choice
      behavior than simple non-probabilistic heuristics. Our experimental design lends
      itself to the general study of model selection in a sensorimotor context as it
      allows to separately query model and parameter variables from subjects.

PMID- 23125828
TI  - Effects of mindful-attention and compassion meditation training on amygdala
      response to emotional stimuli in an ordinary, non-meditative state.
AB  - The amygdala has been repeatedly implicated in emotional processing of both
      positive and negative-valence stimuli. Previous studies suggest that the amygdala
      response to emotional stimuli is lower when the subject is in a meditative state
      of mindful-attention, both in beginner meditators after an 8-week meditation
      intervention and in expert meditators. However, the longitudinal effects of
      meditation training on amygdala responses have not been reported when
      participants are in an ordinary, non-meditative state. In this study, we
      investigated how 8 weeks of training in meditation affects amygdala responses to
      emotional stimuli in subjects when in a non-meditative state. Healthy adults with
      no prior meditation experience took part in 8 weeks of either Mindful Attention
      Training (MAT), Cognitively-Based Compassion Training (CBCT; a program based on
      Tibetan Buddhist compassion meditation practices), or an active control
      intervention. Before and after the intervention, participants underwent an fMRI
      experiment during which they were presented images with positive, negative, and
      neutral emotional valences from the IAPS database while remaining in an ordinary,
      non-meditative state. Using a region-of-interest analysis, we found a
      longitudinal decrease in right amygdala activation in the Mindful Attention group
      in response to positive images, and in response to images of all valences
      overall. In the CBCT group, we found a trend increase in right amygdala response
      to negative images, which was significantly correlated with a decrease in
      depression score. No effects or trends were observed in the control group. This
      finding suggests that the effects of meditation training on emotional processing
      might transfer to non-meditative states. This is consistent with the hypothesis
      that meditation training may induce learning that is not stimulus- or task
      specific, but process-specific, and thereby may result in enduring changes in
      mental function.

PMID- 23125830
TI  - Effect of biomechanical constraints in the hand laterality judgment task: where
      does it come from?
AB  - Several studies have reported that, when subjects have to judge the laterality of
      rotated hand drawings, their judgment is automatically influenced by the
      biomechanical constraints of the upper limbs. The prominent account for this
      effect is that, in order to perform the task, subjects mentally rotate their
      upper limbs toward the position of the displayed stimulus in a way that is
      consistent with the biomechanical constraints underlying the actual movement.
      However, the effect of such biomechanical constraints was also found in the
      responses of motor-impaired individuals performing the hand laterality judgment
      (HLJ) task, which seems at odds with the "motor imagery" account for this effect.
      In this study, we further explored the source of the biomechanical constraint
      effect by assessing the ability of an individual (DC) with a congenital absence
      of upper limbs to judge the laterality of rotated hand or foot drawings. We found
      that DC was as accurate and fast as control participants in judging the
      laterality of both hand and foot drawings, without any disadvantage for hands
      when compared to feet. Furthermore, DC's response latencies (RLs) for hand
      drawings were influenced by the biomechanical constraints of hand movements in
      the same way as control participants' RLs. These results suggest that the effect
      of biomechanical constraints in the HLJ task is not strictly dependent on "motor
      imagery" and can arise from the visual processing of body parts being sensitive
      to such constraints.

PMID- 23125829
TI  - Enactive cinema paves way for understanding complex real-time social interaction
      in neuroimaging experiments.
AB  - We outline general theoretical and practical implications of what we promote as
      enactive cinema for the neuroscientific study of online socio-emotional
      interaction. In a real-time functional magnetic resonance imaging (rt-fMRI)
      setting, participants are immersed in cinematic experiences that simulate social
      situations. While viewing, their physiological reactions-including brain
      responses-are tracked, representing implicit and unconscious experiences of the
      on-going social situations. These reactions, in turn, are analyzed in real-time
      and fed back to modify the cinematic sequences they are viewing while being
      scanned. Due to the engaging cinematic content, the proposed setting focuses on
      living-by in terms of shared psycho-physiological epiphenomena of experience
      rather than active coping in terms of goal-oriented motor actions. It constitutes
      a means to parametrically modify stimuli that depict social situations and their
      broader environmental contexts. As an alternative to studying the variation of
      brain responses as a function of a priori fixed stimuli, this method can be
      applied to survey the range of stimuli that evoke similar responses across
      participants at particular brain regions of interest.

PMID- 23125831
TI  - An investigation of dendritic delay in octopus cells of the mammalian cochlear
      nucleus.
AB  - Octopus cells, located in the mammalian auditory brainstem, receive their
      excitatory synaptic input exclusively from auditory nerve fibers (ANFs). They
      respond with accurately timed spikes but are broadly tuned for sound frequency.
      Since the representation of information in the auditory nerve is well understood,
      it is possible to pose a number of questions about the relationship between the
      intrinsic electrophysiology, dendritic morphology, synaptic connectivity, and the
      ultimate functional role of octopus cells in the brainstem. This study employed a
      multi-compartmental Hodgkin-Huxley model to determine whether dendritic delay in
      octopus cells improves synaptic input coincidence detection in octopus cells by
      compensating for the cochlear traveling wave delay. The propagation time of post
      synaptic potentials from synapse to soma was investigated. We found that the
      total dendritic delay was approximately 0.275 ms. It was observed that low
      threshold potassium channels in the dendrites reduce the amplitude dependence of
      the dendritic delay of post-synaptic potentials. As our hypothesis predicted, the
      model was most sensitive to acoustic onset events, such as the glottal pulses in
      speech when the synaptic inputs were arranged such that the model's dendritic
      delay compensated for the cochlear traveling wave delay across the ANFs. The
      range of sound frequency input from ANFs was also investigated. The results
      suggested that input to octopus cells is dominated by high frequency ANFs.

PMID- 23125833
TI  - Aging specifically impairs switching to an allocentric navigational strategy.
AB  - Navigation abilities decline with age, partly due to deficits in numerous
      component processes. Impaired switching between these various processes (i.e.,
      switching navigational strategies) is also likely to contribute to age-related
      navigational impairments. We tested young and old participants on a virtual plus
      maze task (VPM), expecting older participants to exhibit a specific strategy
      switching deficit, despite unimpaired learning of allocentric (place) and
      egocentric (response) strategies following reversals within each strategy. Our
      initial results suggested that older participants performed worse during place
      trial blocks but not response trial blocks, as well as in trial blocks following
      a strategy switch but not those following a reversal. However, we then separated
      trial blocks by both strategy and change type, revealing that these initial
      results were due to a more specific deficit in switching to the place strategy.
      Place reversals and switches to response, as well as response reversals, were
      unaffected. We argue that this specific "switch-to-place" deficit could account
      for apparent impairments in both navigational strategy switching and allocentric
      processing and contributes more generally to age-related decline in navigation.

PMID- 23125834
TI  - Potential drug mechanism(s) targeting the contractile status of hepatic stellate
      cells.

PMID- 23125832
TI  - The computational power of astrocyte mediated synaptic plasticity.
AB  - Research in the last two decades has made clear that astrocytes play a crucial
      role in the brain beyond their functions in energy metabolism and homeostasis.
      Many studies have shown that astrocytes can dynamically modulate neuronal
      excitability and synaptic plasticity, and might participate in higher brain
      functions like learning and memory. With the plethora of astrocyte mediated
      signaling processes described in the literature today, the current challenge is
      to identify, which of these processes happen under what physiological condition,
      and how this shapes information processing and, ultimately, behavior. To answer
      these questions will require a combination of advanced physiological, genetical,
      and behavioral experiments. Additionally, mathematical modeling will prove
      crucial for testing predictions on the possible functions of astrocytes in
      neuronal networks, and to generate novel ideas as to how astrocytes can
      contribute to the complexity of the brain. Here, we aim to provide an outline of
      how astrocytes can interact with neurons. We do this by reviewing recent
      experimental literature on astrocyte-neuron interactions, discussing the dynamic
      effects of astrocytes on neuronal excitability and short- and long-term synaptic
      plasticity. Finally, we will outline the potential computational functions that
      astrocyte-neuron interactions can serve in the brain. We will discuss how
      astrocytes could govern metaplasticity in the brain, how they might organize the
      clustering of synaptic inputs, and how they could function as memory elements for
      neuronal activity. We conclude that astrocytes can enhance the computational
      power of neuronal networks in previously unexpected ways.

PMID- 23125835
TI  - Ocular drug delivery: a clue from nanotechnology.

PMID- 23125836
TI  - Group I metabotropic glutamate receptor-mediated gene transcription and
      implications for synaptic plasticity and diseases.
AB  - Stimulation of group I metabotropic glutamate receptors (mGluRs) initiates a wide
      variety of signaling pathways. Group I mGluR activation can regulate gene
      expression at both translational and transcriptional levels, and induces
      translation or transcription-dependent synaptic plastic changes in neurons. The
      group I mGluR-mediated translation-dependent neural plasticity has been well
      reviewed. In this review, we will highlight group I mGluR-induced gene
      transcription and its role in synaptic plasticity. The signaling pathways (PKA,
      CaMKs, and MAPKs) which have been shown to link group I mGluRs to gene
      transcription, the relevant transcription factors (CREB and NF-kappaB), and
      target proteins (FMRP and ARC) will be documented. The significance and future
      direction for characterizing group I mGluR-mediated gene transcription in fragile
      X syndrome, schizophrenia, drug addiction, and other neurological disorders will
      also be discussed.

PMID- 23125837
TI  - From form to function: the role of Nox4 in the cardiovascular system.
AB  - The NADPH oxidase (Nox) family of proteins is comprised of seven members,
      including Noxes1-5 and the Duoxes 1 and 2. Nox4 is readily distinguished from the
      other Nox isoforms by its high level of expression in cardiovascular tissues and
      unique enzymatic properties. Nox4 is constitutively active and the amount of
      reactive oxygen species (ROS) contributed by Nox4 is primarily regulated at the
      transcriptional level although there is recent evidence for post-translational
      control. Nox4 emits a different pattern of ROS and its subcellular localizations,
      tissue distribution and influence over signaling pathways is different from the
      other Nox enzymes. Previous investigations have revealed that Nox4 is involved in
      oxygen sensing, vasomotor control, cellular proliferation, differentiation,
      migration, apoptosis, senescence, fibrosis, and angiogenesis. Elevated expression
      of Nox4 has been reported in a number of cardiovascular diseases, including
      atherosclerosis, pulmonary fibrosis, and hypertension, cardiac failure and
      ischemic stroke. However, many important questions remain regarding the
      functional significance of Nox4 in health and disease, including the role of Nox4
      subcellular localization and its downstream targets. The goal of this review is
      to summarize the recent literature on the genetic and enzymatic regulation,
      subcellular localization, signaling pathways, and the role of Nox4 in
      cardiovascular disease states.

PMID- 23125839
TI  - Stress "deafness" in a Language with Fixed Word Stress: An ERP Study on Polish.
AB  - The aim of the present contribution was to examine the factors influencing the
      prosodic processing in a language with predictable word stress. For Polish, a
      language with fixed penultimate stress but several well-defined exceptions,
      difficulties in the processing and representation of prosodic information have
      been reported (e.g., Peperkamp and Dupoux, 2002). The present study utilized
      event-related potentials (ERPs) to investigate the factors influencing prosodic
      processing in Polish. These factors are (i) the predictability of stress and (ii)
      the prosodic structure in terms of metrical feet. Polish native speakers were
      presented with correctly and incorrectly stressed Polish words and instructed to
      judge the correctness of the perceived stress patterns. For some stress
      violations, an early negativity was found which was interpreted as a reflection
      of an error-detection mechanism. In addition, exceptional stress patterns
      (=antepenultimate stress) and post-lexical (=initial) stress evoked a task
      related positivity effect (P300) whose amplitude and latency is correlated with
      the degree of anomaly and deviation from an expectation. In contrast, violations
      involving the default (=penultimate stress) did not produce such an effect. This
      asymmetrical result is interpreted to reflect that Polish native speakers are
      less sensitive to the default pattern than to the exceptional or post-lexical
      patterns. Behavioral results are orthogonal to the electrophysiological results
      showing that Polish speakers had difficulties to reject any kind of stress
      violation. Thus, on a meta-linguistic level Polish speakers appeared to be stress
      "deaf" for any kind of stress manipulation, whereas the neural reactions
      differentiate between the default and lexicalized patterns.

PMID- 23125840
TI  - Mechano-Growth Factor: an important cog or a loose screw in the repair machinery?

PMID- 23125838
TI  - Towards solving the riddle of forgetting in functional amnesia: recent advances
      and current opinions.
AB  - Remembering the past is a core feature of human beings, enabling them to maintain
      a sense of wholeness and identity and preparing them for the demands of the
      future. Forgetting operates in a dynamic neural connection with remembering,
      allowing the elimination of unnecessary or irrelevant information overload and
      decreasing interference. Stress and traumatic experiences could affect this
      connection, resulting in memory disturbances, such as functional amnesia. An
      overview of clinical, epidemiological, neuropsychological, and neurobiological
      aspects of functional amnesia is presented, by preponderantly resorting to own
      data from patients with functional amnesia. Patients were investigated medically,
      neuropsychologically, and neuroradiologically. A detailed report of a new case is
      included to illustrate the challenges posed by making an accurate differential
      diagnosis of functional amnesia, a condition that may encroach on the boundaries
      between psychiatry and neurology. Several mechanisms may play a role in
      "forgetting" in functional amnesia, such as retrieval impairments, consolidating
      defects, motivated forgetting, deficits in binding and reassembling details of
      the past, deficits in establishing a first person autonoetic connection with
      personal events, and loss of information. In a substantial number of patients, we
      observed a synchronization abnormality between a frontal lobe system, important
      for autonoetic consciousness, and a temporo-amygdalar system, important for
      evaluation and emotions, which provides empirical support for an underlying
      mechanism of dissociation (a failure of integration between cognition and
      emotion). This observation suggests a mnestic blockade in functional amnesia that
      is triggered by psychological or environmental stress and is underpinned by a
      stress hormone mediated synchronization abnormality during retrieval between
      processing of affect-laden events and fact-processing.

PMID- 23125842
TI  - Macrophages in inflammation and its resolution.

PMID- 23125841
TI  - Characterization of staufen1 ribonucleoproteins by mass spectrometry and
      biochemical analyses reveal the presence of diverse host proteins associated with
      human immunodeficiency virus type 1.
AB  - The human immunodeficiency virus type 1 (HIV-1) unspliced, 9 kb genomic RNA
      (vRNA) is exported from the nucleus for the synthesis of viral structural
      proteins and enzymes (Gag and Gag/Pol) and is then transported to sites of virus
      assembly where it is packaged into progeny virions. vRNA co-exists in the
      cytoplasm in the context of the HIV-1 ribonucleoprotein (RNP) that is currently
      defined by the presence of Gag and several host proteins including the double
      stranded RNA-binding protein, Staufen1. In this study we isolated Staufen1 RNP
      complexes derived from HIV-1-expressing cells using tandem affinity purification
      and have identified multiple host protein components by mass spectrometry. Four
      viral proteins, including Gag, Gag/Pol, Env and Nef as well as >200 host proteins
      were identified in these RNPs. Moreover, HIV-1 induces both qualitative and
      quantitative differences in host protein content in these RNPs. 22% of Staufen1
      associated factors are virion-associated suggesting that the RNP could be a
      vehicle to achieve this. In addition, we provide evidence on how HIV-1 modulates
      the composition of cytoplasmic Staufen1 RNPs. Biochemical fractionation by
      density gradient analyses revealed new facets on the assembly of Staufen1 RNPs.
      The assembly of dense Staufen1 RNPs that contain Gag and several host proteins
      were found to be entirely RNA-dependent but their assembly appeared to be
      independent of Gag expression. Gag-containing complexes fractionated into a
      lighter and another, more dense pool. Lastly, Staufen1 depletion studies
      demonstrated that the previously characterized Staufen1 HIV-1-dependent RNPs are
      most likely aggregates of smaller RNPs that accumulate at juxtanuclear domains.
      The molecular characterization of Staufen1 HIV-1 RNPs will offer important
      information on virus-host cell interactions and on the elucidation of the
      function of these RNPs for the transport of Gag and the fate of the unspliced
      vRNA in HIV-1-producing cells.

PMID- 23125844
TI  - Expression of ROS-responsive genes and transcription factors after metabolic
      formation of H(2)O(2) in chloroplasts.
AB  - Glycolate oxidase (GO) catalyses the oxidation of glycolate to glyoxylate,
      thereby consuming O(2) and producing H(2)O(2). In this work, Arabidopsis thaliana
      plants expressing GO in the chloroplasts (GO plants) were used to assess the
      expressional behavior of reactive oxygen species (ROS)-responsive genes and
      transcription factors (TFs) after metabolic induction of H(2)O(2) formation in
      chloroplasts. In this organelle, GO uses the glycolate derived from the oxygenase
      activity of RubisCO. Here, to identify genes responding to an abrupt production
      of H(2)O(2) in chloroplasts we used quantitative real-time PCR (qRT-PCR) to test
      the expression of 187 ROS-responsive genes and 1880 TFs after transferring GO and
      wild-type (WT) plants grown at high CO(2) levels to ambient CO(2) concentration.
      Our data revealed coordinated expression changes of genes of specific functional
      networks 0.5 h after metabolic induction of H(2)O(2) production in GO plants,
      including the induction of indole glucosinolate and camalexin biosynthesis genes.
      Comparative analysis using available microarray data suggests that signals for
      the induction of these genes through H(2)O(2) may originate in the chloroplast.
      The TF profiling indicated an up-regulation in GO plants of a group of genes
      involved in the regulation of proanthocyanidin and anthocyanin biosynthesis.
      Moreover, the upregulation of expression of TF and TF-interacting proteins
      affecting development (e.g., cell division, stem branching, flowering time,
      flower development) would impact growth and reproductive capacity, resulting in
      altered development under conditions that promote the formation of H(2)O(2).

PMID- 23125843
TI  - Role of KIR3DS1 in human diseases.
AB  - The function of natural killer (NK) cells is controlled by several activating and
      inhibitory receptors, including the family of killer-immunoglobulin-like
      receptors (KIRs). One distinctive feature of KIRs is the extensive number of
      various haplotypes generated by the gene content within the KIR gene locus as
      well as by highly polymorphic members of the KIR gene family, namely KIR3DL1/S1.
      Within the KIR3DL1/S1 gene locus, KIR3DS1 represents a conserved allelic variant
      and displays other unique features in comparison to the highly polymorphic
      KIR3DL1 allele. KIR3DS1 is present in all human populations and belongs to the
      KIR haplotype group B. KIR3DS1 encodes for an activating receptor featuring the
      characteristic short cytoplasmic tail and a positively charged residue within the
      transmembrane domain, which allows recruitment of the ITAM-bearing adaptor
      molecule DAP12. Although HLA class I molecules are thought to represent natural
      KIR ligands, and HLA-Bw4 molecules serve as ligands for KIR3DL1, the ligand for
      KIR3DS1 still needs to be identified. Despite the lack of formal evidence for an
      interaction of KIR3DS1 with HLA-Bw4-I80 or any other HLA class I subtype to date,
      a growing number of associations between the presence of KIR3DS1 and the outcome
      of viral infections have been described. Especially, the potential protective
      role of KIR3DS1 in combination with HLA-Bw4-I80 in the context of HIV-1 infection
      has been studied intensively. In addition, a number of recent studies have
      associated the presence or absence of KIR3DS1 with the occurrence and outcome of
      some malignancies, autoimmune diseases, and graft-versus-host disease (GVHD). In
      this review, we summarize the present knowledge regarding the characteristics of
      KIRD3S1 and discuss its role in various human diseases.

PMID- 23125846
TI  - Validation of genome-wide intervertebral disk calcification associations in
      dachshund and further investigation of the chromosome 12 susceptibility locus.
AB  - Herniation of the intervertebral disk is a common cause of neurological
      dysfunction in the dog, particularly in the Dachshund. Using the Illumina
      CanineHD BeadChip, we have previously identified a major locus on canine
      chromosome 12 nucleotide positions 36,750,205-38,524,449 that strongly associates
      with intervertebral disk calcification in Danish wire-haired Dachshunds. In this
      study, targeted resequencing identified two synonymous variants in MB21D1 and one
      in the 5'-untranslated region of KCNQ5 that associates with intervertebral disk
      calcification in an independent sample of wire-haired Dachshunds. Haploview
      identified seven linkage disequilibrium blocks across the disease-associated
      region. The effect of haplotype windows on disk calcification shows that all
      haplotype windows are significantly associated with disk calcification. However,
      our predictions imply that the causal variant(s) are most likely to be found
      between nucleotide 36,750,205-37,494,845 as this region explains the highest
      proportion of variance in the dataset. Finally, we develop a risk prediction
      model for wire-haired Dachshunds. We validated the association of the chromosome
      12 locus with disk calcification in an independent sample of wire-haired
      Dachshunds and identify potential risk variants. Additionally, we estimated
      haplotype effects and set up a model for prediction of disk calcifications in
      wire-haired Dachshunds based on genotype data. This genetic prediction model may
      prove useful in selection of breeding animals in future breeding programs.

PMID- 23125845
TI  - Clinical implications of human population differences in genome-wide rates of
      functional genotypes.
AB  - There have been a number of recent successes in the use of whole genome
      sequencing and sophisticated bioinformatics techniques to identify pathogenic DNA
      sequence variants responsible for individual idiopathic congenital conditions.
      However, the success of this identification process is heavily influenced by the
      ancestry or genetic background of a patient with an idiopathic condition. This is
      so because potential pathogenic variants in a patient's genome must be contrasted
      with variants in a reference set of genomes made up of other individuals' genomes
      of the same ancestry as the patient. We explored the effect of ignoring the
      ancestries of both an individual patient and the individuals used to construct
      reference genomes. We pursued this exploration in two major steps. We first
      considered variation in the per-genome number and rates of likely functional
      derived (i.e., non-ancestral, based on the chimp genome) single nucleotide
      variants and small indels in 52 individual whole human genomes sampled from 10
      different global populations. We took advantage of a suite of computational and
      bioinformatics techniques to predict the functional effect of over 24 million
      genomic variants, both coding and non-coding, across these genomes. We found that
      the typical human genome harbors ~5.5-6.1 million total derived variants, of
      which ~12,000 are likely to have a functional effect (~5000 coding and ~7000 non
      coding). We also found that the rates of functional genotypes per the total
      number of genotypes in individual whole genomes differ dramatically between human
      populations. We then created tables showing how the use of comparator or
      reference genome panels comprised of genomes from individuals that do not have
      the same ancestral background as a patient can negatively impact pathogenic
      variant identification. Our results have important implications for clinical
      sequencing initiatives.

PMID- 23125847
TI  - Pharmacological and Toxicological Advances in PPAR-Related Medicines.

PMID- 23125849
TI  - Pantoprazole before Endoscopy in Patients with Gastroduodenal Ulcer Bleeding:
      Does the duration of Infusion and Ulcer Location Influence the Effects?
AB  - The aim of this study was to investigate the effect of preemptive pantoprazole
      infusion on early endoscopic findings in patients with acute ulcer bleeding.
      Records of 333 patients admitted with acute ulcer bleeding were analyzed. Ulcer
      bleeders were given either 80 mg bolus of pantoprazole followed by continuous
      infusion of 8 mg per hour or saline infusion until endoscopy. In 93 patients
      saline infusion whereas in 240 patients bolus plus infusion of pantoprazole was
      administrated with mean (+/-SD) durations of 5.45 +/- 12.9 hours and 6.9 +/- 13.2
      hours, respectively (P = 0.29). Actively bleeding ulcers were detected in 46/240
      (19.2%) of cases in the pantoprazole group as compared with 23/93 (24.7%) in the
      saline infusion group (P = 0.26). Different durations of pantoprazole infusion (0
      4 hours, >4 hours, and >6 hours) had no significant effect on endoscopic and
      clinical outcome parameters in duodenal ulcer bleeders. Gastric ulcer bleeders on
      pantoprazole infusion longer than 4 and 6 hours before endoscopy had actively
      bleeding ulcers in 4.3% and 5% compared to the 19.5% active bleeding rate in the
      saline group (P = 0.02 and P = 0.04). Preemptive infusion of high-dose
      pantoprazole longer than 4 hours before endoscopy decreased the ratio of active
      bleeding only in gastric but not in duodenal ulcer patients.

PMID- 23125848
TI  - Influence of tumour necrosis factor alpha on the outcome of ischaemic
      postconditioning in the presence of obesity and diabetes.
AB  - Obesity and diabetes contribute to cardiovascular disease and alter cytokine
      profile. The cytokine, tumour necrosis factor alpha (TNFalpha), activates a
      protective signalling cascade during ischaemic postconditioning (IPostC).
      However, most successful clinical studies with IPostC have not included obese
      and/or diabetic patients. We aimed to investigate the influence of TNFalpha on
      the outcome of IPostC in obese or diabetic mice. TNF knockout or wildtype mice
      were fed for 11 weeks with a high carbohydrate diet (HCD) to induce modest
      obesity. Diabetes was induced in a separate group by administration of a single
      intraperitoneal injection of streptozotocin. Hearts were then isolated and
      subjected to ischaemia (35 min of global ischaemia) followed by 45 min of
      reperfusion. HCD increased body weight, plasma insulin and leptin levels while
      the glucose level was unchanged. In streptozotocin-treated mice, blood glucose,
      plasma leptin and insulin were altered. Control, obese or diabetic mice were
      protected with IPostC in wiltype animals. In TNF knockout mice, IPostC failed to
      protect control and diabetic hearts while a slight protection was observed in
      obese hearts. Our data confirm a bidirectional role for TNFalpha associated with
      the severity of concomitant comorbidities and suggest that diabetic and/or
      modestly obese patients may still benefit from IPostC.

PMID- 23125850
TI  - Desmoplasia in pancreatic cancer. Can we fight it?
AB  - The hallmark of pancreatic tumours, the desmoplastic reaction, provides a unique
      microenvironment that affects pancreatic tumour behaviour, its ability to grow
      and metastasize as well as resist the effects of chemotherapy. Complex molecular
      interactions and pathways give rise to the desmoplastic reaction. Breakdown or
      penetration of the desmoplastic reaction may hold the key to overcoming the
      limits of delivery of efficacious chemotherapy or the development of new targeted
      treatments. Herein we discuss such new developments to fight the desmoplastic
      reaction, including inhibitors of the epidermal growth factor, fibroblast growth
      factor, the hedgehog pathway, as well as new molecular targets like CD40 agonist
      and its effects on T cells, extracellular matrix modifying enzymes such as LOXL2
      inhibitor and novel tumour penetrating peptides for delivery of drugs.

PMID- 23125851
TI  - Association between Habitual Dietary Salt Intake and Risk of Gastric Cancer: A
      Systematic Review of Observational Studies.
AB  - Purpose. Systematic reviews of case-control and prospective studies showed a
      positive association between habitual salt intake and gastric cancer. Given new
      studies published thereafter, we carried out a meta-analysis to assess the
      association between dietary salt intake and gastric cancer. Methods. Case-control
      studies and cohort studies published between January 1992 and January 2012 on
      PubMed and Embase were searched. We quantified associations between salt intake
      and gastric cancer with meta-analysis. Results. Eleven studies (7 case controls
      and 4 cohorts) finally were included in the meta-analysis (total population: n =
      2076498; events: n = 12039). The combined odds ratio showed significantly
      positive association between high salt intake and gastric cancer compared with
      low salt intake (OR = 2.05, 95% CI [1.60, 2.62]; P < 0.00001). In subgroup meta
      analysis, findings were slightly different when analyses were restricted to salty
      food intake (OR = 2.41, 95% CI [2.08, 2.78]; P < 0.00001) as well as in Asia (OR
      = 1.27 95% CI [1.22, 1.32]; P < 0.00001). There was no evidence that sample size,
      exposure assessment substantially influenced the estimate of effects.
      Conclusions. The systemic review supports the hypothesis that dietary salt intake
      is positively associated with the risk of gastric cancer.

PMID- 23125852
TI  - Influence of Rosiglitazone on the Expression of PPARgamma, NF-kappaB, and TNF
      alpha in Rat Model of Ulcerative Colitis.
AB  - Aim. To observe the disease activity index (DAI) and the colonic mucosa damage
      index (CMDI), detect the colonic mucosal expression of PPARgamma, NF-kappaB, and
      TNF-alpha in rats with ulcerative colitis (UC), and to investigate the protective
      role of rosiglitazone in UC. Methods. Sprague-Dawley (SD) rats were divided into
      three groups: a control group, a rosiglitazone treatment group, and a UC model
      group. Rats were sacrificed on days 7, 14, 21, or 35 following administration of
      treatment after enema and DAI, CMDI and colonic expression of PPARgamma, NF
      kappaB, and TNF-alpha were assessed. Results. In the UC model group, DAI, CDMI
      and the colonic expression of NF-kappaB and TNF-alpha increased significantly
      compared to the control group at all timepoints, but PPARgamma decreased
      significantly. Furthermore, in the rosiglitazone treatment group, DAI and CMDI
      decreased significantly on the 14-day, 21-day, and 35-day timepoints compared to
      the UC model group; the colonic expression of NF-kappaB and TNF-alpha decreased
      compared to UC model group at all timepoints, but the PPARgamma expression
      increased significantly. Conclusions. Rosiglitazone can alleviate colonic mucosal
      inflammation and have the protective role on UC by upregulating PPARgamma
      expression and downregulating NF-kappaB and TNF-alpha expression.

PMID- 23125853
TI  - Anxiolytic and Antidepressant-Like Effects of the Aqueous Extract of Alafia
      multiflora Stem Barks in Rodents.
AB  - The present study examined the anxiolytic and antidepressant effects of the
      aqueous extract of Alafia multiflora Stapf (AM) stem barks (150 and 300 mg/kg, 7
      days administration) on rats and mice, using experimental paradigms of anxiety
      and depression. In the open field, the aqueous extract increased significantly
      the number of center square crossed and the time spent at the center of the field
      as well as the rearing time, while the grooming time was reduced significantly.
      In the elevated plus maze, the aqueous extract increased the time spent and the
      number of entries in the open arms. All these effects were also completely
      reversed by flumazenil, an antagonist of benzodiazepine receptors and pindolol a
      beta-adrenoceptors blocker/5-HT 1A/1B receptor antagonist. The time spent in the
      light compartment, the latency time, and the number of the light-dark transitions
      increased significantly in the light/dark exploration test after the treatment
      with AM. The extract was able to reduce significantly the immobility time and
      increase swimming as well as climbing duration. Taken together, the present work
      evidenced anxiolytic effects of the aqueous extract of AM that might involve an
      action on benzodiazepine-type receptors and an antidepressant effect where
      noradrenergic mechanisms will probably play a role.

PMID- 23125854
TI  - Safety assessment of zigbir(r): a polyherbal formulation in sprague-dawley rats.
AB  - The safety of Zigbir(r), a polyherbal formulation intended for use as food
      supplement, was evaluated in Sprague-Dawley rats treated orally at the dose of
      2000 mg/kg in acute and at 250, 500, and 1000 mg/kg for 90 days in subchronic
      toxicity study. The median lethal dose of Zigbir(r) was found to be more than
      2000 mg/kg, and fourteen-day repeated dose toxicity study revealed it to be safe
      up to 1000 mg/kg. The subchronic study did not show any mortality or treatment
      related adverse clinical signs. The treated animals exhibited normal feed intake
      and comparable body weight gain except for a decrease in females of 500 and 1000
      mg/kg groups. Ocular examination revealed no abnormalities. Further, Zigbir(r)
      administration in rats did not induce any major changes in urinalysis,
      hematological, and biochemical evaluations except for minor alterations in few
      parameters at different dose levels. Gross and histopathological findings did not
      show any lesions attributable to Zigbir(r) administration. The no observed effect
      level of Zigbir(r) was found to be 500 and 250 mg/kg in male and female Sprague
      Dawley rats.

PMID- 23125855
TI  - Medical applications of clostridia and clostridial toxins.

PMID- 23125856
TI  - Update of assessment of survival in head and neck cancer after regional
      recurrence.
AB  - Objective. To evaluate site of regional recurrence in patients with squamous cell
      carcinoma of upper aerodigestive tract after neck dissection and the results of
      salvage treatment. Methods. 95 patients with regional recurrence as the first
      manifestation of relapse were selected between 943 patients who underwent neck
      dissection. We evaluated level and side of recurrence, as well disease control
      after salvage treatment. Results. Level II was the most frequent site of
      recurrence. Salvage treatment was performed in 51% of ipsilateral and in 75% of
      contralateral (nondissected neck) recurrences. Control of the disease 12 months
      after salvage surgery was 25% in the ipsilateral and 37% in contralateral
      recurrences. Conclusions. Cervical recurrences occur predominantly in level II.
      Relapse in level I is frequent only in oral cavity tumors and relapse in level V
      is rare. The neck recurrence carries a poor prognosis even among patients who
      underwent retreatment with curative intent.

PMID- 23125858
TI  - Selenium in the prevention of anthracycline-induced cardiac toxicity in children
      with cancer.
AB  - High cumulative doses of anthracyclines (300-500 mg/m(2)) used in the treatment
      of children with cancer may result in cardiotoxicity, a major long-term adverse
      effect that limits clinical usefulness of this class of chemotherapeutic agents.
      We assessed anthracycline-induced cardiotoxicity by measuring Pro-BNP levels and
      echocardiographic (ECHO) findings and investigated potential protective effect of
      selenium (Se) supplementation in a group of pediatric cancer patients. Plasma
      level of Pro-BNP was measured, and ECHO was performed in 67 patients (45 boys, 22
      girls; ages 2-18 years; median age 12 years) after they completed anthracycline
      containing chemotherapy. Serum Se level was measured in 37 patients. Eleven
      patients had high Pro-BNP levels and/or cardiac failure with Pro-BNP levels of 10
      8,022 pg/mL (median 226.3 pg/mL; laboratory normal level is less than 120 pg/mL).
      Serum Se levels were low (20-129 mcg/L, median 62 mcg/L) in ten of these eleven
      patients. Eight of 10 patients with low Se and high Pro-BNP levels were
      supplemented with Se 100 mcg/day for a period of 4-33 months (median 6 months)
      which resulted in improvement in Pro-BNP and/or ECHO findings. These results
      suggest that Se supplementation may have a role in protection against
      anthracycline-induced cardiac toxicity.

PMID- 23125857
TI  - Adrenocortical Carcinoma: Current Therapeutic State-of-the-Art.
AB  - Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy that generally
      conveys a poor prognosis. Currently, surgical resection is considered the lone
      curative treatment modality. In addition, the low prevalence of ACC has limited
      effective clinical trial design to develop evidence-based approaches to ACC
      therapy. The proper role of radio- and chemotherapy treatment for ACC is still
      being defined. Similarly, the molecular pathogenesis of ACC remains to be fully
      characterized. Despite these challenges, progress has been made in several areas.
      After years of refinement, an internationally accepted staging system has been
      defined. International collaborations have facilitated increasingly robust
      clinical trials, especially regarding agent choice and patient selection for
      chemotherapeutics. Genetic array data and molecular profiling have identified new
      potential targets for rational drug design as well as potential tumor markers and
      predictors of therapeutic response. However, these advances have not yet been
      translated into a large outcomes benefit for ACC patients. In this paper, we
      summarize established therapy for ACC and highlight recent findings in the field
      that are impacting clinical practice.

PMID- 23125860
TI  - Fertility preservation in female cancer patients.

PMID- 23125859
TI  - Folate Intake, MTHFR Polymorphisms, and the Risk of Colorectal Cancer: A
      Systematic Review and Meta-Analysis.
AB  - Background. The objective was to determine whether relationships exist between
      the methylene-tetrahydrofolate reductase (MTHFR) polymorphisms and risk of
      colorectal cancer (CRC) and examine whether the risk is modified by level of
      folate intake. Methods. MEDLINE, Embase, and SCOPUS were searched to May 2012
      using the terms "folic acid," "folate," "colorectal cancer,"
      "methylenetetrahydrofolate reductase," "MTHFR." Observational studies were
      included which (1) assessed the risk of CRC for each polymorphism and/or (2) had
      defined levels of folate intake for each polymorphism and assessed the risk of
      CRC. Results. From 910 references, 67 studies met our criteria; hand searching
      yielded 10 studies. The summary risk estimate comparing the 677CT versus CC
      genotype was 1.02 (95% CI 0.95-1.10) and for 677TT versus CC was 0.88 (95% CI
      0.80-0.96) both with heterogeneity. The summary risk estimates for A1298C
      polymorphisms suggested no reduced risk. The summary risk estimate for high
      versus low total folate for the 677CC genotype was 0.70 (95% CI 0.56-0.89) and
      the 677TT genotype 0.63 (95% CI 0.41-0.97). Conclusion. These results suggest
      that the 677TT genotype is associated with a reduced risk of developing CRC,
      under conditions of high total folate intake, and this associated risk remains
      reduced for both MTHFR 677 CC and TT genotypes.

PMID- 23125861
TI  - Hemiballismus, Hyperphagia, and Behavioral Changes following Subthalamic Infarct.
AB  - The function of subthalamic nucleus (STN) which is a part of the basal ganglia
      system is not clear, but it is hypothesized that this component might be involved
      in action selection. Unilateral damage to STN, which can commonly occur due to
      the small vessel stroke mainly, causes hemiballismus and sometimes hemichorea
      hemiballismus. This paper deals with a 60-year-old patient with sudden onset of
      abnormal movements in his right limbs. He had increased appetite and hyperphagia
      and also developed mood and behavioral changes (aggressiveness, irritability,
      anxiety, and sometimes obscene speech). The magnetic resonance imaging revealed
      infarct area in left subthalamus. In our case, hemiballismus is caused by
      infarction in left subthalamic area. Occurrence of irritability, anxiety, and
      some behavioral changes such as aggressiveness and obscene speech can be
      explained by impairment of STN role in nonmotor behavior and cognitive function
      as a result of infarct.

PMID- 23125862
TI  - Congenital transmission by protozoan.

PMID- 23125863
TI  - Factors contributing to urban malaria transmission in sub-saharan Africa: a
      systematic review.
AB  - Sub-Saharan Africa suffers by far the greatest malaria burden worldwide and is
      currently undergoing a profound demographic change, with a growing proportion of
      its population moving to urban areas. Urbanisation is generally expected to
      reduce malaria transmission; however the disease still persists in African
      cities, in some cases at higher levels than in nearby rural areas. Objective.
      This paper aims to collate and analyse risk factors for urban malaria
      transmission throughout sub-Saharan Africa and to discuss their implications for
      control. Methods. A systematic search on malaria and urbanisation was carried out
      focusing on sub-Saharan Africa. Particular interest was taken in vector breeding
      sites in urban and periurban areas. Results. A variety of urban vector breeding
      sites were catalogued, the majority of which were artificial, including urban
      agriculture, tyre tracks, and ditches. Natural breeding sites varied according to
      location. Low socioeconomic status was a significant risk factor for malaria,
      often present in peri-urban areas. A worrying trend was seen in the adaptation of
      malaria vector species to the urban environment. Urban malaria is highly focused
      and control programs should reflect this. Conclusion. As urbanisation continues
      and vector species adapt, continued monitoring and control of urban malaria in
      sub-Saharan Africa is essential.

PMID- 23125864
TI  - The Effect of Second-Language Experience on Native-Language Processing.
AB  - Previous work on bilingual language processing indicates that native-language
      skills can influence second-language acquisition. The goal of the present work
      was to examine the influence of second-language experiences on native-language
      vocabulary and reading skills in two groups of bilingual speakers. English
      Spanish and English-Mandarin bilingual adults were tested on vocabulary knowledge
      and reading fluency in English, their native language. Participants also provided
      detailed information regarding their history of second-language acquisition,
      including age of L2 acquisition, degree of L2 exposure, L2 proficiency, and
      preference of L2 use. Comparisons across the two bilingual groups revealed that
      both groups performed similarly on native-language vocabulary and reading
      measures. However, in English-Spanish bilinguals, higher self-reported reading
      skills in Spanish were associated with higher English reading-fluency scores,
      while in English-Mandarin bilinguals, higher self-reported reading skills in
      Mandarin were associated with lower English reading-fluency scores. These
      findings suggest that second-language experiences influence native-language
      performance, and can facilitate or reduce it depending on the properties of the
      second-language writing system.

PMID- 23125865
TI  - Expression of the autoimmune regulator gene and its relevance to the mechanisms
      of central and peripheral tolerance.
AB  - The autoimmune polyendocrine syndrome type 1 (APS-1) is a monogenic disease due
      to pathogenic variants occurring in the autoimmune regulator (AIRE) gene. Its
      related protein, AIRE, activates the transcription of genes encoding for tissue
      specific antigens (TsAgs) in a subset of medullary thymic epithelial cells: the
      presentation of TsAgs to the maturating thymocytes induces the apoptosis of the
      autoreactive clones and constitutes the main form of central tolerance.
      Dysregulation of thymic AIRE expression in genetically transmitted and acquired
      diseases other than APS-1 may contribute to further forms of autoimmunity. As
      AIRE and its murine homolog are also expressed in the secondary lymphoid organs,
      the extent and relevance of AIRE participation in the mechanisms of peripheral
      tolerance need to be thoroughly defined.

PMID- 23125867
TI  - Antidiabetic Effects of Add-On Gynostemma pentaphyllum Extract Therapy with
      Sulfonylureas in Type 2 Diabetic Patients.
AB  - Aims. To investigate the antidiabetic effect of the traditional Vietnamese herb
      Gynostemma pentaphyllum (GP) together with sulfonylurea (SU) in 25 drug-naive
      type 2 diabetic patients. Methods. After 4-week treatment with gliclazide (SU),
      30 mg daily, all patients were randomly assigned into 2 groups to add on GP
      extract or placebo extract, 6 g daily, during eight weeks. Results. After 4-week
      SU treatment, fasting plasma glucose (FPG) and HbA(1C) decreased significantly (P
      < 0.001). FPG was further reduced after add-on therapy with 2.9 +/- 1.7 and 0.9
      +/- 0.6 mmol/L in the GP and placebo groups, respectively (P < 0.001). Therapy
      with GP extract also reduced 30- and 120-minute oral glucose tolerance test
      postload values. HbA(1C) levels decreased approximately 2% units in the GP group
      compared to 0.7% unit in the placebo group (P < 0.001). Conclusion. GP extract in
      addition to SU offers an alternative to addition of other oral medication to
      treat type 2 diabetic patients.

PMID- 23125866
TI  - TRAF1 gene polymorphism correlates with the titre of Gp210 antibody in patients
      with primary biliary cirrhosis.
AB  - BACKGROUND: Polymorphisms of TRAF1 (Tumor necrosis factor receptor-associated
      factor 1) are associated with rheumatoid arthritis (RA). Whether TRAF1
      polymorphisms confer increased risk for primary biliary cirrhosis (PBC), an
      autoimmune liver disease which can co-exist with RA, is unknown. AIM OF THE
      STUDY: To assess the frequency of the RA-conferring susceptibility TRAF1
      polymorphisms rs3761847 and rs2900180 in a cohort of PBC patients. The
      association of TRAF1 polymorphisms with clinical features and autoantibody
      markers was also analyzed. METHODS: We studied 179 PBC patients and 300 controls.
      Samples were genotyped for TRAF1 gene polymorphisms by real-time PCR.
      Autoantibodies were tested by ELISA. RESULTS: The frequency of rs3761847 and
      rs2900180 polymorphisms did not differ between patients and controls. Laboratory
      or clinical features were not associated with specific polymorphisms. Gp210
      autoantibody titres were conspicuously higher among GG homozygotes of rs3761847
      as compared with AA homozygotes (P = 0.02). In contrast, antichromatin titers
      were higher in AA compared to GG rs3761847 homozygotes (P = 0.04). Rheumatoid
      factor IgG titres were significantly higher in rs2900180 TT homozygotes than CC
      homozygotes (P = 0.02). CONCLUSIONS: TRAF1 polymorphisms occur with the similar
      frequency in PBC patients and in the general population, but their presence is
      probably involved in the regulation of specific PBC-related autoantibodies.

PMID- 23125868
TI  - Cardioprotective Effects of 20(S)-Ginsenoside Rh2 against Doxorubicin-Induced
      Cardiotoxicity In Vitro and In Vivo.
AB  - Doxorubicin (DOX) is considered as one of the best antineoplastic agents.
      However, its clinical use is restricted by its associated cardiotoxicity, which
      is mediated by the production of reactive oxygen species. In this study, 20(S)
      ginsenoside Rh2 (Rh2) was explored whether it had protective effects against DOX
      induced cardiotoxicity. In vitro study on H9C2 cell line, as well as in vivo
      investigation in one mouse and one rat model of DOX-induced cardiomyopathy, was
      carried out. The results showed that pretreatment with Rh2 significantly
      increased the viability of DOX-injured H9C2 cells. In the mouse model, Rh2 could
      suppress the DOX-induced release of the cardiac enzymes into serum and improved
      the occurred pathological changes through ameliorating the decreased antioxidant
      biomolecules and the cumulated lipid peroxidation malondialdehyde in heart
      tissues. In the rat model, Rh2 could attenuate the change of ECG resulting from
      DOX administration. Furthermore, Rh2 enhanced the antitumor activity of DOX in
      A549 cells. Our findings thus demonstrated that Rh2 pretreatment could
      effectively alleviate heart injury induced by DOX, and Rh2 might act as a novel
      protective agent in the clinical usefulness of DOX.

PMID- 23125869
TI  - Acetone Extract from Rhodomyrtus tomentosa: A Potent Natural Antioxidant.
AB  - Rhodomyrtus tomentosa (Myrtaceae) has been employed in traditional Thai medicine
      to treat colic diarrhoea, dysentery, abscesses, haemorrhage, and gynaecopathy. In
      addition, it has been used to formulate skin-whitening, anti-aging and skin
      beautifying agents. Ethnomedical activities of this plant may be due its
      antioxidant property. Hence, the aim of this study was to evaluate both in vitro
      and in vivo antioxidant activities of R. tomentosa leaf extract. In vitro
      antioxidant activity of the extract was assessed by lipid peroxidation inhibition
      capacity, ferric reducing antioxidant power, and metal chelating activity. R.
      tomentosa extract demonstrated its free radical scavenging effects in
      concentration dependent manner. In vivo antioxidant activity of the extract was
      conducted in Swiss Albino mice. Levels of thio-barbituric acid reactive
      substances (TBARS), glutathione (GSH), and the activities of antioxidant enzymes
      including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase
      (GPx) in blood, liver, and kidney were analyzed using microtitre plate
      photometer. Administration of CCl(4) caused significant increase in TBARS and
      decrease in GSH, SOD, CAT and GPx levels. In contrast, R. tomentosa extract (0.8
      g/kg) effectively prevented these alterations and maintained the antioxidant
      status. The results suggest that R. tomentosa extract can serve as a potent
      antioxidant.

PMID- 23125870
TI  - Yoga & cancer interventions: a review of the clinical significance of patient
      reported outcomes for cancer survivors.
AB  - Limited research suggests yoga may be a viable gentle physical activity option
      with a variety of health-related quality of life, psychosocial and symptom
      management benefits. The purpose of this review was to determine the clinical
      significance of patient-reported outcomes from yoga interventions conducted with
      cancer survivors. A total of 25 published yoga intervention studies for cancer
      survivors from 2004-2011 had patient-reported outcomes, including quality of
      life, psychosocial or symptom measures. Thirteen of these studies met the
      necessary criteria to assess clinical significance. Clinical significance for
      each of the outcomes of interest was examined based on 1 standard error of the
      measurement, 0.5 standard deviation, and relative comparative effect sizes and
      their respective confidence intervals. This review describes in detail these
      patient-reported outcomes, how they were obtained, their relative clinical
      significance and implications for both clinical and research settings. Overall,
      clinically significant changes in patient-reported outcomes suggest that yoga
      interventions hold promise for improving cancer survivors' well-being. This
      research overview provides new directions for examining how clinical significance
      can provide a unique context for describing changes in patient-reported outcomes
      from yoga interventions. Researchers are encouraged to employ indices of clinical
      significance in the interpretation and discussion of results from yoga studies.

PMID- 23125871
TI  - Analysis of multiple cell reservoirs expressing unspliced HIV-1 gag-pol mRNA in
      patients on antiretroviral therapy.
AB  - AIMS: Longitudinal percentage change of eight HIV-1 gag-pol mRNA cellular
      reservoirs from HIV-infected subjects on antiretroviral therapy was ascertained
      by simultaneous ultrasensitive subpopulation staining/hybridization in situ
      (SUSHI).  MATERIALS #ENTITYSTARTX00026; METHODS: Serial peripheral blood
      mononuclear cells were taken from three subjects with treatment success, limited
      response and viral breakthrough plasma viral load (PVL) profiles. SUSHI was
      carried out on monocytes, macrophages, CD4(+) cells and naive, memory and
      activated T-cell reservoirs followed with broad light scatter flow cytometry. 
      RESULTS: All gag-pol(+) reservoirs declined in the treatment success patient and
      similar to PVL. Only some gag-pol(+) reservoirs responded similarly to PVL for
      the limited treatment patient, and most gag-pol(+) reservoirs increased 16 weeks
      prior to PVL breakthrough in the viral breakthrough patient.  CONCLUSION: SUSHI
      measures changes in a wide range of gag-pol(+) reservoirs in response to
      antiretroviral therapy.

PMID- 23125872
TI  - Automatic identification of the number of food items in a meal using clustering
      techniques based on the monitoring of swallowing and chewing.
AB  - The number of distinct foods consumed in a meal is of significant clinical
      concern in the study of obesity and other eating disorders. This paper proposes
      the use of information contained in chewing and swallowing sequences for meal
      segmentation by food types. Data collected from experiments of 17 volunteers were
      analyzed using two different clustering techniques. First, an unsupervised
      clustering technique, Affinity Propagation (AP), was used to automatically
      identify the number of segments within a meal. Second, performance of the
      unsupervised AP method was compared to a supervised learning approach based on
      Agglomerative Hierarchical Clustering (AHC). While the AP method was able to
      obtain 90% accuracy in predicting the number of food items, the AHC achieved an
      accuracy >95%. Experimental results suggest that the proposed models of automatic
      meal segmentation may be utilized as part of an integral application for
      objective Monitoring of Ingestive Behavior in free living conditions.

PMID- 23125873
TI  - Automatic food intake detection based on swallowing sounds.
AB  - This paper presents a novel fully automatic food intake detection methodology, an
      important step toward objective monitoring of ingestive behavior. The aim of such
      monitoring is to improve our understanding of eating behaviors associated with
      obesity and eating disorders. The proposed methodology consists of two stages.
      First, acoustic detection of swallowing instances based on mel-scale Fourier
      spectrum features and classification using support vector machines is performed.
      Principal component analysis and a smoothing algorithm are used to improve
      swallowing detection accuracy. Second, the frequency of swallowing is used as a
      predictor for detection of food intake episodes. The proposed methodology was
      tested on data collected from 12 subjects with various degrees of adiposity.
      Average accuracies of >80% and >75% were obtained for intra-subject and inter
      subject models correspondingly with a temporal resolution of 30s. Results
      obtained on 44.1 hours of data with a total of 7305 swallows show that detection
      accuracies are comparable for obese and lean subjects. They also suggest
      feasibility of food intake detection based on swallowing sounds and potential of
      the proposed methodology for automatic monitoring of ingestive behavior. Based on
      a wearable non-invasive acoustic sensor the proposed methodology may potentially
      be used in free-living conditions.

PMID- 23125874
TI  - Is Self-Other Overlap the Key to Understanding Empathy?
AB  - Preston and Hofelich (2012) suggested that researchers disagree on the role of
      self-other overlap in empathy due to a failure to differentiate among neural
      overlap, subjective resonance, and personal distress; they also developed a
      framework for tying neural and subjective overlap to various aspects of
      functioning they include in the construct of empathy. Although we found their
      discussion of different processes that have been labeled empathy interesting and
      helpful, we found their discussion of self-other overlap to be somewhat less
      useful for conceptualizing differences among empathy-related processes. In
      addition, we provide an alternative perspective to their reasoning regarding the
      role of experience and neural overlap in an aspect of empathy-related responding
      (e.g., concern or compassion).

PMID- 23125875
TI  - Attenuated psychosis and the schizophrenia prodrome: current status of risk
      identification and psychosis prevention.
AB  - Recent efforts in the prevention of schizophrenia have focused on defining
      psychosis-risk syndromes and evaluating treatments that can prevent transition to
      psychosis in these ultra-high risk groups. In this review, different kinds of
      prevention approaches are enumerated and necessary conditions for a disease
      prevention strategy are summarized. The broad overlap as well as the significant
      difference between a schizophrenia prodrome and a 'psychosis-risk syndrome' is
      discussed and the present status of approaches to identify individuals at
      increased risk for developing psychosis and schizophrenia are critically examined
      along with evaluations on therapeutic interventions to reduce these risks.
      Finally, to conclude, recommendations for current best clinical practice and key
      questions for the future are suggested.

PMID- 23125876
TI  - TARGETING OF MACROPHAGE FOAM CELLS IN ATHEROSCLEROTIC PLAQUE USING
      OLIGONUCLEOTIDE-FUNCTIONALIZED NANOPARTICLES.
AB  - Macrophage foam cells are key components of atherosclerotic plaque and play an
      important role in the progression of atherosclerosis leading to plaque rupture
      and thrombosis. Foam cells are emerging as attractive targets for therapeutic
      intervention and for imaging the progression of disease. Therefore, designing
      nanoparticles (NPs) targeted to macrophage foam cells in plaque is of
      considerable therapeutic significance. Here we report the construction of an
      oligonucleotide functionalized NP system with high affinity for foam cells.
      Nanoparticles functionalized with a 23-mer poly-Guanine (polyG) oligonucleotide
      are specifically recognized by the scavenger receptors on lipid-laden foam cells
      in vitro and ex vivo. The enhanced uptake of polyG-functionalized NPs by foam
      cells is inhibited in the presence of acetylated-LDL, a known ligand of scavenger
      receptors. Since polyG oligonucleotides are stable in serum and are unlikely to
      induce an immune response, their use for scavenger receptor-mediated targeting of
      macrophage foam cells provides a strategy for targeting atherosclerotic lesions.

PMID- 23125877
TI  - Strategies of preventing ureteral iatrogenic injuries in obstetrics-gynecology.
AB  - The incidence of ureteral lesions varies between 0.1% and 30% depending on the
      type of the surgical intervention. However, the surgical interventions in
      Obstetrics and Gynecology are responsible for 50% of the total iatrogenic
      ureteral lesions. Sadly, only 1/3 of the iatrogenic ureteral lesions are
      recognized during surgeries and 25% of the unrecognized cases of ureteral lesions
      lead towards the loss of the damaged kidney, while a delayed diagnostic may also
      lead to a progressive deterioration of the renal function. On this matter, of
      decreasing the rate of morbidity and the following forensic risks, the
      gynecologist surgeon must be able to anticipate the potential apparition of a
      specific ureteral lesion, based on the known risk factors of the patient, so that
      he can then prevent the iatrogenic ureteral lesion.

PMID- 23125878
TI  - Lipopolysaccharide binding protein (L.B.P.)--an inflammatory marker of prognosis
      in the acute appendicitis.
AB  - LIPOPOLYSACCHARIDE BINDING PROTEIN (LBP) is an important mediator of the
      inflammatory reaction. A multitude of factors can determine the genic
      transcription activation and the increase of the LBP in the blood and the human
      body humours: Il1, Il 6, lipopolysaccharides, Gram-negative bacteria, as well as
      non-infectious agents. This paper is a prospective study performed on 147
      patients admitted for acute appendicitis in 2010-2012 and evaluates the dynamics
      of LBP in acute appendicitis, by identifying the correlations between the pre-
      and post-operatory levels of LBP (up to 72 hours after surgery) and the
      anatomopathological type (i.e. catarrhal, phlegmonous and gangrenous). The mean
      pre-op LBP values are significantly different as to the histopathological result
      (p<0,005). Among the biological inflammatory markers measured in this present
      study, LBP has a dynamics of its own in the catarrhal and phlegmonous
      appendicitis. Thus, if after the surgical removal of the infectious source, the
      leukocites and neutrophiles decrease 72 hrs after surgery, LBP continues an
      ascending curve. The importance of this study consists in the introduction of
      last generation LBP-type inflammatory markers' dosage in the cecal appendix
      pathology. This implementation is brand new in the Romanian surgical practice.
      The good correlation between the LBP pre-op values and the histopathological
      diagnosis of the appendicits form that we discovered during the present study
      opens the way to large-scale use of the biochemical dosage of LBP in the
      management of acute appendicitis.

PMID- 23125879
TI  - Acute rosiglitazone treatment during reperfusion after hyperglycemic stroke is
      neuroprotective not vascular protective.
AB  - Reperfusion therapy for ischemic stroke can cause secondary brain injury,
      especially under hyperglycemic (HG) conditions. Here we investigated the effect
      of acute treatment with rosiglitazone, a peroxisome proliferator-activated
      receptor-gamma (PPAR-gamma) agonist, prior to postischemic reperfusion, on stroke
      outcome during HG stroke. Male Wistar rats that were either normoglycemic (NG) or
      HG by STZ (50 mg/kg; for 5-6 days) underwent middle cerebral artery occlusion
      (MCAO) for 2 hours with 2 hours of reperfusion. Animals were treated i.v. with
      rosiglitazone (1mg/kg; n=16), rosiglitazone (1mg/kg) + the free radical scavenger
      Tempol (50mg/kg; n=10) or vehicle (n=16) ten minutes prior to reperfusion and
      infarct volume, edema formation and cerebral blood flow (CBF) were measured.
      Compared to NG, HG stroke significantly increased infarct volume from 5.2+/-3.0%
      vs. 14.7+/-3.6% (p<0.05). Rosiglitazone prevented the increased infarct volume
      induced by HG that was only 6.9+/-2.0% (p<0.05 vs. HG) but did not have any
      effect on edema formation that was increased by 3.0% in both HG vehicle and
      rosiglitazone-treated ipsilateral vs. contralateral hemispheres (p<0.05).
      Combined treatment of rosiglitazone + Tempol did not significantly change brain
      water content that remained 2.2% greater than contralateral (p<0.05), but
      reversed the neuroprotective properties of rosiglitazone in HG MCAO animals such
      that infarct volume was 14.3+/-4.4% (p>0.05 vs. vehicle). The lack of an effect
      of combined treatment of rosiglitazone + Temple may be due to a decrease in
      reperfusion CBF that was only 60% of baseline (p<0.01) compared to 82% and 89%
      for HG vehicle and rosiglitazone treated animals (p>0.05). In conclusion, acute
      rosiglitazone treatment prior reperfusion was neuroprotective but not vascular
      protective during HG stroke. 

PMID- 23125880
TI  - Differential Effects for Sexual Risk Behavior: An Application of Finite Mixture
      Regression.
AB  - Understanding the multiple factors that place individuals at risk for sexual risk
      behavior is critical for developing effective intervention programs. Regression
      based methods are commonly used to estimate the average effects of risk factors,
      however such results can be difficult to translate to prevention implications at
      the individual level. Although differential effects can be examined to some
      extent by including interaction terms, as risk factors and moderators are added
      to the model interpretation can become difficult. The current study presents
      finite mixture regression as an alternative approach, where population subgroups
      are identified based on the pattern of associations between multiple risk factors
      and sexual risk behavior. Data from participants in the National Longitudinal
      Study on Adolescent Health were used to explore the effects of five adolescent
      risk factors (early sexual debut, heavy episodic drinking, school connectedness,
      positive consequences of having sex, and negative consequences of having sex) on
      the total number of sexual partners in adulthood. Four latent classes were
      identified on the basis of the Poisson regression parameter estimates. Gender,
      race, and grade were included as predictors of latent class membership. Results
      suggest that prevention programs focused on mediating these particular risk
      factors may be most effective for adolescents who are at lower risk for later
      engaging in risky sexual behaviour; however, for the subgroup of adolescents who
      go on to have the most sexual partners, the evidence is less conclusive and
      warrants further study.

PMID- 23125881
TI  - Management and Treatment Guidelines for Sepsis in Pediatric Patients.
AB  - Sepsis remains one of the leading causes of morbidity and mortality in children
      despite improved understanding of the pathophysiology leading to better clinical
      management and survival. Recent studies have identified several areas that must
      be addressed by the clinician in order to continue to impact the morbidity and
      mortality associated with sepsis. In this review, we discuss the evidence in
      several of these areas including initial resuscitation, pathogen eradication,
      maintenance of oxygen delivery, and directed modifiers of the inflammatory
      response. Our overall goal is to provide the bedside clinician with an updated
      systematic approach to treat sepsis in children.

PMID- 23125882
TI  - Effective use of small-interfering RNA to characterize residual B-cell non
      Hodgkin lymphoma cells following chemotherapy.
AB  - BACKGROUND: Children diagnosed with non-Hodgkin lymphoma (NHL) respond well to
      therapy resulting in relatively good prognosis. The exceptions are those who
      continue to have minimal residual disease (MRD). MRD NHL cells have been
      characterized as having increased mitochondrial DNA (mtDNA) copy numbers with
      increased expression of citrate synthase and isocitrate dehydrogenase. A proof-of
      concept was designed to use small-interfering RNA (siRNA) as a tool to elucidate
      the relationship between citrate synthase and isocitrate dehydrogenase with
      cancer cell integrity.  METHODS: mtDNA copy number and lactate dehydrogenase
      activities were assessed in chemotherapy-exposed residual NHL cells after
      introduction of siRNA against citrate synthase and/or isocitrate dehydrogenase
      expression.  RESULTS: There was a significant decrease in lactate production in
      cells transfected with citrate synthase siRNA (p=0.02). Citrate synthase-silenced
      cells had decreased mtDNA copy numbers (p=0.03) compared to isocitrate
      dehydrogenase-silenced cells or combined citrate synthase- and isocitrate
      dehydrogenase-silenced cells.  CONCLUSION: Inhibition of citrate synthase
      expression in siRNA-treated NHL cells resulted in decreased mtDNA copy numbers
      and lactate dehydrogenase expression. This observation needs further validation
      to determine the role of citrate synthase in mtDNA integrity and if citrate
      synthase siRNA could be a potential therapeutic modality in eradicating residual
      B-NHL cells.

PMID- 23125883
TI  - Epidemiology and Management of Depression Following Coronary Heart Disease
      Diagnosis in Women.
AB  - Coronary heart disease (CHD) and depression are both highly prevalent in women.
      Importantly, depression is associated with significantly elevated morbidity and
      mortality in women with CHD. There are intriguing speculations about biological
      mechanisms underlying this association, such as endothelial dysfunction,
      subclinical atherosclerosis, inflammation, and autonomic dysregulation. Social
      and behavioral mechanisms, such as lack of social support and physical
      inactivity, have also been shown to play important roles. Unfortunately, many
      randomized clinical trials of counseling and pharmacologic interventions for
      depression in patients with CHD have failed to improve cardiovascular outcomes,
      and in fact have raised the possibility that interventions might be harmful in
      women. Several recent trials of new treatment strategies, however, have been more
      effective in improving depressive symptoms and quality of life and deserve
      further investigation. In this review, we summarize recent findings with regards
      to the epidemiology, etiology, diagnosis, and management of depression in women
      diagnosed with CHD.

PMID- 23125884
TI  - Longitudinal analysis of serum miR-122 in a rat model of Wilson's disease.
AB  - PURPOSE: MicroRNA-122 (miR-122) has recently been shown to represent a novel
      biomarker of liver disease. However, the presence of serum miR-122 after liver
      injury was mostly studied at singular time points. The course of serum miR-122
      was determined at consecutive time points during the onset of disease. METHODS:
      Fulminant hepatitis was induced by a high-copper diet in Long-Evans Cinnamon
      (LEC) rats that were used as models for Wilson's disease (WD). Levels of serum
      miR-122, alanine aminotransferase (ALT), aspartate aminotransferase (AST),
      bilirubin, and liver histology were determined. RESULTS: Toxic copper given to
      isolated hepatocytes induced release of miR-122 into the tissue culture medium.
      Levels of serum miR-122 were highly elevated (21.9 +/- 5) in LEC rats after high
      copper diet in fulminant hepatitis, whereas healthy rats showed low (<0.6)
      baseline levels of miR-122. Levels of miR-122 in the serum of LEC rats after high
      copper diet continuously increased for about 4 weeks prior to the onset of
      fulminant hepatitis. In most of the animals (77.8%), significantly increased
      levels of miR-122 were detected about 2 weeks (13.7 +/- 2 days) earlier as
      compared to hepatitis-associated serum markers ALT, AST, and bilirubin. Analysis
      of miR-122 in survivors after cell-based therapy of WD demonstrated a rapid
      decrease of miR-122 levels following hepatocyte transplantation. miR-122
      expression in the serum was normalized to baseline levels in most of the (4/5)
      survivors. CONCLUSION: Our results suggest that longitudinal analysis of miR-122
      allows detection of severe liver disease at an early stage and might be
      excellently suited to monitor therapy, at least when severe liver disease can be
      restored as observed after cell-based therapy of WD. ELECTRONIC SUPPLEMENTARY
      MATERIAL: The online version of this article (doi:10.1007/s12072-012-9348-5)
      contains supplementary material, which is available to authorized users.

PMID- 23125885
TI  - Lipodissolve for body sculpting: safety, effectiveness, and patient satisfaction.
AB  - Lipodissolve, to reduce superficial deposits of fat, has gained popularity in
      recent years. A simple solution of phosphatidylcholine in deoxycholate evolved
      around 2004 and has been used by two collaborating physicians in Minnesota. Their
      experience encompassing 1,616 patients receiving a total of 15,122 treatments is
      described. Relatively modest volumes of injections produced satisfactory and
      smooth results in 74.5 to 86.5 percent of the patients in the two practices. No
      serious complications developed. Minor and rare side effects included pain,
      lightheadedness, tender nodules, pigmentation, and ulceration in two patients.
      The authors offer useful tips to enhance safety, effectiveness, and patient
      satisfaction with the procedure.

PMID- 23125886
TI  - Efficacy and safety of a low-molecular weight hyaluronic Acid topical gel in the
      treatment of facial seborrheic dermatitis.
AB  - OBJECTIVE: Hyaluronic acid sodium salt gel 0.2% is a topical device effective in
      reducing skin inflammation. Facial seborrheic dermatitis, characterized by
      erythema and or flaking/scaling in areas of high sebaceous activity, affects up
      to five percent of the United States population. Despite ongoing studies, the
      cause of the condition is yet unknown, but has been associated with yeast
      colonization and resultant immune-derived inflammation. First-line management
      typically is with topical steroids as well as the immunosuppressant agents
      pimecrolimus and tacrolimus. The objective of this study was to evaluate the
      efficacy and safety of a topical anti-inflammatory containing low-molecular
      weight hyaluronic acid. DESIGN AND SETTING: Prospective, observational, non
      blinded safety and efficacy study in an outpatient setting. PARTICIPANTS:
      Individuals 18 to 75 years of age with facial seborrheic dermatitis.
      MEASUREMENTS: Outcome measures included scale, erythema, pruritus, and the
      provider global assessment, which were all measured on a five-point scale.
      Subjects were assessed at Baseline, Week 2, Week 4, and Week 8. RESULTS: Interim
      data for 7 of 15 subjects are presented. Hyaluronic acid sodium salt gel 0.2% was
      shown through visual grading assessments to improve the provider global
      assessment by 47.62 percent from Baseline to Week 4. Reductions in scale,
      erythema, and pruritus were 66.67, 50, and 60 percent, respectively at Week 4. At
      Week 8, the provider global assessment was improved from baseline in 100 percent
      of subjects. CONCLUSION: Treatment with topical low-molecular weight hyaluronic
      acid resulted in improvement in the measured endpoints. Topical low-molecular
      weight hyaluronic acid is another option that may be considered for the treatment
      of facial seborrheic dermatitis in the adult population. Compliance and tolerance
      were excellent.

PMID- 23125887
TI  - Osteopathic manipulative treatment: novel application to dermatological disease.
AB  - Dermatological diseases, such as dysesthesia syndromes, stasis dermatoses, and
      hyperhidrosis are difficult to treat due to their complex etiologies. Current
      theories suggest these diseases are caused by physiological imbalances, such as
      nerve impingement, localized tissue congestion, and impaired autonomic
      regulation. Osteopathic manipulative therapy targets these physiological
      dysfunctions and may serve as a beneficial therapeutic option. Osteopathic
      manipulative therapy techniques include high velocity low amplitude, muscle
      energy, counterstrain, myofascial release, craniosacral, and lymphatic drainage.
      An osteopathic manipulative therapy technique is chosen based on its
      physiological target for a particular disease. Osteopathic manipulative therapy
      may be useful alone or in combination with standard therapeutic options. However,
      due to the lack of standardized trials supporting the efficacy of osteopathic
      manipulative therapy treatment for dermatological disease, randomized, well
      controlled studies are necessary to confirm its therapeutic value.

PMID- 23125888
TI  - Invasive ductal breast carcinoma underneath a lipoma in a male patient.
AB  - Male breast cancer is a rare malignancy and accounts for less than one percent of
      all cancers in men. The authors describe the case of a 76-year-old Caucasian man
      with invasive ductal breast carcinoma who presented with a common lipoma. This
      paper reviews the current literature on epidemiology, risk factors, etiology,
      different types of breast cancer, clinical presentation, imaging, diagnostic
      workup, and treatment.

PMID- 23125889
TI  - Lymphocytic thrombophilic arteritis induced by minocycline.
AB  - Lymphocytic thrombophilic arteritis is an entity only recently defined in the
      literature. This term describes a distinctive histopathological combination of
      lymphocytic vascular inflammation associated with a hyalinized fibrin ring in the
      vessel lumina, changes reflecting a thrombophilic endovasculitis. The authors
      present the case of a woman who developed lymphocytic thrombophilic arteritis
      coinciding with the use of minocycline. In addition to these histopathological
      findings, the cutaneous manifestations of this case reflect previously reported
      clinical findings of progressive localized livedo racemosa characterized by
      reticular patchy hyperpigmentation predominately affecting the lower extremities.

PMID- 23125890
TI  - Sister Mary joseph nodule as a presenting sign of pancreatobiliary
      adenocarcinoma.
AB  - Sister Mary Joseph nodules represent metastatic cancer of the umbilicus. These
      malignancies are usually associated with the ovary and gastrointestinal tract.
      The authors report the case of a Sister Mary Joseph nodule originating from the
      bifurcation of the common hepatic duct. Umbilical nodules should prompt clinical
      evaluations, as these tumors are usually associated with poor prognosis.

PMID- 23125891
TI  - Acute painful nodules in a young healthy adult.

PMID- 23125892
TI  - Effects of temperature and water-filtered infrared-A alone or in combination on
      healthy and glyoxal-stressed fibroblast cultures.
AB  - Water-filtered infrared-A (wIRA) radiation has been described as supportive for
      tissue regeneration. We sought to investigate in detail the wIRA effect at
      different temperatures in 3T3 fibroblasts that were treated with glyoxal to
      induce formation of advanced glycation end products (AGEs). Nonirradiated and
      nonglyoxal-treated cells served as controls. Experiments were carried out over a
      range of 37 degrees -45 degrees C with exact temperature monitoring to
      distinguish between temperature and wIRA effects. Metabolic activity was assessed
      by resazurin assay. Mitochondrial membrane potential was assessed by JC-1 vital
      staining. Apoptotic changes were determined by vital staining with annexin V and
      YO-PRO-1 and determination of subG1 DNA content. Temperature had a dominant
      effect overriding effects exerted by wIRA or glyoxal treatment. The number of
      apoptotic cells was significantly higher at 45 degrees C, while the percentage of
      healthy cells was significantly lower at 45 degrees C. WIRA irradiation itself or
      in combination with glyoxal treatment exerted no damaging effects on the
      fibroblasts at physiological (37 degrees -40 degrees C) or higher (42 degrees -45
      degrees C) temperatures compared to untreated controls. Temperatures of 45
      degrees C, which can occur during inappropriate application of infrared
      irradiation, damage cells even in the absence of wIRA or glyoxal application.

PMID- 23125893
TI  - Hypoxia-induced oxidative stress in ischemic retinopathy.
AB  - Oxidative stress plays a crucial role in the pathogenesis of retinal
      ischemia/hypoxia, a complication of ocular diseases such as diabetic retinopathy
      (DR) and retinopathy of prematurity (ROP). Oxidative stress refers to the
      imbalance between the production of reactive oxygen species (ROS) and the ability
      to scavenge these ROS by endogenous antioxidative systems. Free radicals and ROS
      are implicated in the irreversible damage to cell membrane, DNA, and other
      cellular structures by oxidizing lipids, proteins, and nucleic acids. Anti
      oxidants that can inhibit the oxidative processes can protect retinal cells from
      ischemic/hypoxic insults. In particular, treatment using anti-oxidants such as
      vitamin E and lutein, inhibition of nicotinamide adenine dinucleotide phosphate
      oxidase (NADPH oxidase) or related signaling pathways, and administration of
      catalase and superoxide dismutase (SOD) are possible therapeutic regimens for DR,
      ROP, and other retinal ischemic diseases. The role of oxidative stress in the
      pathogenesis of DR and ROP as well as the underlying mechanisms involved in the
      hypoxia/ischemia-induced oxidative damage is discussed. The information provided
      will be beneficial in understanding the underlying mechanisms involved in the
      pathogenesis of the diseases as well as in developing effective therapeutic
      interventions to treat oxidative stress-induced damages.

PMID- 23125894
TI  - Protein oxidative damage at the crossroads of cellular senescence, aging, and age
      related diseases.
AB  - Protein damage mediated by oxidation, protein adducts formation with advanced
      glycated end products and with products of lipid peroxidation, has been
      implicated during aging and age-related diseases, such as neurodegenerative
      diseases. Increased protein modification has also been described upon replicative
      senescence of human fibroblasts, a valid model for studying aging in vitro.
      However, the mechanisms by which these modified proteins could impact on the
      development of the senescent phenotype and the pathogenesis of age-related
      diseases remain elusive. In this study, we performed in silico approaches to
      evidence molecular actors and cellular pathways affected by these damaged
      proteins. A database of proteins modified by carbonylation, glycation, and lipid
      peroxidation products during aging and age-related diseases was built and
      compared to those proteins identified during cellular replicative senescence in
      vitro. Common cellular pathways evidenced by enzymes involved in intermediate
      metabolism were found to be targeted by these modifications, although different
      tissues have been examined. These results underscore the potential effect of
      protein modification in the impairment of cellular metabolism during aging and
      age-related diseases.

PMID- 23125895
TI  - Diagnosis and management of Barrett's metaplasia: What's new.
AB  - Barrett's esophagus (BE) is a complication of gastroesophageal reflux disease,
      and a premalignant lesion for esophageal adenocarcinoma (EAC). Observational
      studies suggest that endoscopic surveillance is associated with the detection of
      dysplasia and EAC at an early stage along with improved survival, but
      controversies still remain. The management of patients with BE involves
      endoscopic surveillance, preventive and clinical measures for cancer, and
      endoscopic and surgical approaches to treatment. Deciding upon the most
      appropriate treatment is a challenge. This study presents the results and the
      effectiveness of these practices.

PMID- 23125896
TI  - Role of narrow band imaging in endoscopic submucosal dissection.
AB  - Narrow band imaging (NBI) is a new image enhancement system employing optic
      digital methods to enhance images of blood vessels on mucosal surfaces, allowing
      improved visualization of mucosal surface structures. Studies have progressed
      over the last several years, and the clinical usefulness has been demonstrated.
      NBI has become frequently applied for preoperative diagnosis before endoscopic
      submucosal dissection (ESD) of digestive tract cancers, as well as for assessment
      of the range of ESD for en-bloc resection of large lesions. Consensus has been
      reached with regard to the usefulness of NBI for detecting micro-lesions of
      esophageal squamous cell carcinoma indicated for ESD, for the diagnosis of the
      range and depth. NBI has also been attracting attention for diagnosing gastric
      cancer based on the observation of micro blood vessels on the mucosal surface and
      mucosal surface microstructures. The usefulness of NBI has been reported in
      relation to various aspects of colon cancer, including diagnoses of the presence,
      quality, range, and depth of lesions. However, as NBI has not surpassed
      diagnostic methods based on magnifying observation combined with the established
      and widely employed dye method, its role in ESD is limited at present. Although
      NBI is very useful for the diagnosis of digestive tract cancers, comprehensive
      endoscopic diagnosis employing the combination of conventional endoscopy
      including dye spraying, EUS, and NBI may be important and essential for ESD.

PMID- 23125897
TI  - Comparison between needle-knife fistulotomy and standard cannulation in ERCP.
AB  - AIM: To compare the rates of success and complications of two different methods
      of access into the common bile duct (CBD). METHODS: Between October 2007 and
      November 2008, 173 consecutive patients (71 men, 102 women, mean age 68.6 years)
      requiring endoscopic retrograde cannulation of the papilla and endoscopic
      treatment were studied. In the first 88 patients CBD cannulation was performed
      through supra-papillary fistulotomy (group F); in the following 85 patients
      standard cannulation was performed through the Oddi sphincter (group S).
      Indications for the procedure were: choledocholithiasis, biliary obstruction,
      postoperative leak, sclerosing cholangitis, and Mirizzi's syndrome. RESULTS: Deep
      CBD cannulation was successful in 85/88 patients (96.5%) in group F vs 60/85
      patients (70.6%) in group S (P < 0.0001). The remaining 25 group S patients in
      whom cannulation failed were shifted to fistulotomy. Fistulotomy was successful
      in 21/25 patients (84%). As for complications, hyperamilasemia occurred in 7
      (7.9%) group F patients vs 7 (8.2%) group S patients (P = NS); mild pancreatitis
      in 1 (1.1%) group F patient vs 5 (5.8%) group S patients (P = NS); bleeding in 3
      (3.4%) group F patients vs 3 (3.5%) group S patients (P = NS). CONCLUSION: Needle
      knife fistulotomy should represent either the first approach to therapeutic
      cannulation or rescue therapy after unsuccessful standard cannulation.

PMID- 23125898
TI  - Fully covered self-expandable metal stents for treatment of malignant and benign
      biliary strictures.
AB  - AIM: To present a series of covered self-expandable metal stents (CSEMS) placed
      for different indications and to evaluate the effectiveness, complications and
      extractability of these devices. METHODS: We therefore retrospectively reviewed
      the courses of patients who received CSEMS due to malignant as well as benign
      biliary strictures and post-sphincterotomy bleeding in our endoscopic unit
      between January 2010 and October 2011. RESULTS: Twenty-six patients received 28
      stents due to different indications (20 stents due to malignant biliary
      strictures, six stents due to benign biliary strictures and two stents due to
      post-sphincterotomy bleeding). Biliary obstruction was relieved in all cases,
      regardless of the underlying cause. Hemostasis could be achieved in the two
      patients who received the stents for this purpose. Complications occurred in five
      patients (18%). Two patients (7%) developed cholecystitis, stents
      dislocated/migrated in other two patients (7%), and in one patient (3.6%) stent
      occlusion was documented during the study period. Seven stents were extracted
      endoscopically. Removal of stents was easily possible in all cases in which it
      was desired using standard forceps. Twelve patients underwent surgery with
      pylorus preserving duodenopancreatectomy. In all patients stents could be removed
      during the operation without difficulties. CONCLUSION: Despite the higher costs
      of these devices, fully covered self-expanding metal stents may be suitable to
      relief biliary obstruction due to bile duct stenosis, regardless of the
      underlying cause. CSEMS may also represent an effective treatment strategy of
      severe post-sphincterotomy bleeding, not controlled by other measures.

PMID- 23125899
TI  - Impact of antiplatelet treatment on colorectal cancer staging characteristics.
AB  - AIM: To evaluate whether antiplatelet medication leads to an earlier stage
      colorectal cancer (CRC) diagnosis. METHODS: From January 2002 until March 2010,
      patients that presented to our institution with the initial diagnosis of CRC and
      were submitted to an open curative CRC resection or a palliative procedure were
      retrospectively reviewed. Exclusion criteria were the use of antithrombotic
      medication, i.e., coumarins, and appendiceal malignancies. Data acquired from
      medical files included age, gender, past medical history, antithrombotic
      treatment received prior to endoscopic diagnosis, preoperative imaging staging,
      location of the tumor, surgical and final histopathological report. Patients that
      did not receive any antithrombotic medication prior to the endoscopic diagnosis
      comprised the control group of the study, while patients that were on
      antiplatelet medication comprised the antiplatelet group. Primary end point was a
      comparison of CRC stage in the two groups of the study. CRC presenting symptoms
      and the incidence of each cancer stage in the two groups were also evaluated.
      RESULTS: A total of 387 patients with the diagnosis of CRC were submitted to our
      department for further surgical treatment. Ninety-eight patients (25.32%), with a
      median age of 71 years (range 52-91 years), were included in the antiplatelet
      group, while 289 (74.67%) patients, with a median age of 67 years (range 41-90
      years), were not in any thrombosis prophylaxis medication (control group). Thirty
      one patients were treated with some kind of palliative procedure, either
      endoscopic, such as endoscopic stent placement, or surgical, such as de
      compressive colostomy or deviation. Coronary disease (77.55% - 76 patients),
      stroke recurrence prevention (14.28% - 14 patients) and peripheral arterial
      disease (8.16% - 8 patients) were the indications for the administration of
      antiplatelet treatment (aspirin, clopidogrel, ticlopidine or dipyridamole) in the
      antiplatelet group. All patients on aspirin treatment received a dosage of 100
      mg/d, while the minimum prophylactic dosages were also used for the rest of the
      antiplatelet drugs. Investigation of an iron deficiency anemia (147 patients),
      per rectum blood loss (84 patients), bowel obstruction and/or perforation (81
      patients), bowel habits alterations (32 patients), non-specific symptoms, such as
      weight loss, intermittent abdominal pain and fatigue, (22 patients) or population
      screening (21 patients) were the indications for the endoscopic investigation in
      both groups. Bleeding, either chronic presenting as anemia or acute was
      significantly higher (P = 0.002) for the antiplatelet arm of the study (71
      patients - 72.4% of the antiplatelet group vs 160 patients - 55.3% of the control
      group). The mean tumor, node and metastasis stage was 2.57 +/- 0.96 for the
      control group, 2.27 +/- 0.93 for the antiplatelet group (P = 0.007) and 2.19 +/-
      0.92 for the subgroup of patients taking aspirin (P = 0.003). The incidence of
      advanced disease (stage IV) was lower for the antiplatelet group of the study (P
      = 0.033). CONCLUSION: The adverse effect of bleeding that is justifiably attached
      to this drug category seems to have a favorable impact on the staging
      characteristics of CRC.

PMID- 23125900
TI  - Diagnostic accuracy of confocal laser endomicroscopy in diagnosing dysplasia in
      patients affected by long-standing ulcerative colitis.
AB  - AIM: To evaluate the diagnostic accuracy of confocal laser endomicroscopy (CLE)
      for the detection of dysplasia in long-standing ulcerative colitis (UC). METHODS:
      We prospectively performed a surveillance colonoscopy in 51 patients affected by
      long-standing UC. Also, in the presence of macroscopic areas with suspected
      dysplasia, both targeted contrasted indigo carmine endoscopic assessment and
      probe-based CLE were performed. Colic mucosal biopsies and histology, utilised as
      the gold standard, were assessed randomly and on visible lesions, in accordance
      with current guidelines. RESULTS: Fourteen of the 51 patients (27%) showed
      macroscopic mucosal alterations with the suspected presence of dysplasia, needing
      chromoendoscopic and CLE evaluation. In 5 macroscopically suspected cases, the
      presence of dysplasia was confirmed by histology (3 flat dysplasia; 2 DALMs). No
      dysplasia/cancer was found on any of the outstanding random biopsies. The
      diagnostic accuracy of CLE for the detection of dysplasia compared to standard
      histology was sensitivity 100%, specificity 90%, positive predictive value 83%
      and negative predictive value 100%. CONCLUSION: CLE is an accurate tool for the
      detection of dysplasia in long-standing UC and shows optimal values of
      sensitivity and negative predictivity. The scheduled combined application of
      chromoendoscopy and CLE could maximize the endoscopic diagnostic accuracy for
      diagnosis of dysplasia in UC patients, thus limiting the need for biopsies.

PMID- 23125901
TI  - Efficacy of computed image modification of capsule endoscopy in patients with
      obscure gastrointestinal bleeding.
AB  - AIM: To investigate whether flexible spectral color enhancement (FICE) improves
      diagnostic yields of capsule endoscopy (CE) for obscure gastro-intestinal
      bleeding (OGIB). METHODS: The study subjects consisted of 81 patients. Using
      FICE, there were three different sets with different wavelengths. Using randomly
      selected sets of FICE, images of CE were evaluated again by two individuals who
      were not shown the conventional CE reports and findings. The difference between
      FICE and conventional imaging was examined. RESULTS: The overall diagnostic
      yields in FICE sets 1, 2, 3 and conventional imaging (48.1%) were 51.9%, 40.7%,
      51.9% and 48.1%, respectively, which showed no statistical difference compared to
      conventional imaging. The total numbers of detected lesions per examination in
      FICE imaging and conventional imaging were 2.5 +/- 2.1 and 1.8 +/- 1.7,
      respectively, which showed a significant difference (P = 0.01). CONCLUSION: The
      diagnostic yield for OGIB is not improved by FICE. However, FICE can detect
      significantly more small bowel lesions compared to conventional imaging.

PMID- 23125902
TI  - Basketing a basket: A novel emergency rescue technique.
AB  - Fracture of the central lead wire of an impacted basket during a mechanical
      lithotripsy for large common bile duct (CBD) stones poses a special challenge.
      Different maneuvers have been described to resolve this problem. Most techniques
      require equipment or facilities which may not be readily available in small
      community hospitals. We present here a similar situation in a patient with a
      large stone at the level of the cystic duct. Through the duodenoscope, a smaller
      Dormia basket was introduced into the CBD along the side of the impacted broken
      basket. The tip of the impacted basket was grasped and, by pulling downwards, the
      basket was disengaged from the stone. The two baskets were then removed
      successfully. We suggest this simple technique should be tried initially, before
      resorting to more advanced procedures.

PMID- 23125903
TI  - Mucosal hyperplasia in an uncovered portion of partially covered metal stent.
AB  - Covered self-expandable metal stents were developed to overcome tumor in-growth
      through the metal mesh. Stent migration is one of their malfunctions. Recently,
      the partially covered wallflex stent (PCWS) was developed with flared ends to
      prevent migration However, difficulty has been reported in its removal. We
      describe the removal of a PCWS embedded in mucosal hyperplasia at the uncovered
      proximal flared end, visualized by using SpyGlass cholangioscopy.

PMID- 23125904
TI  - Submucosal hematoma is a highly suggestive finding for amyloid light-chain
      amyloidosis: Two case reports.
AB  - The clinical and endoscopic features of amyloid light-chain (AL) amyloidosis are
      diverse and mimic various other diseases. Endoscopically, few reports on
      submucosal hematomas of the gastrointestinal (GI) tract are available in the
      literature. Here, we report two cases of AL amyloidosis presenting as submucosal
      hematomas in the absence of clinical disease elsewhere in the body. The 2 cases
      were referred to our hospital because of hematochezia. The endoscopic findings in
      both cases were similar in submucosal hematoma formation. However, the clinical
      courses differed. In the first case, there was no evidence of systemic
      amyloidosis and the disease was conservatively managed. In the second case, the
      disease progressed to systemic amyloidosis and the patient died within a short
      time. We conclude that the endoscopic detection of a submucosal hematoma in the
      setting of GI bleeding should raise suspicion of AL amyloidosis. Referral to a
      hematologist should be done immediately for treatment while the involvement is
      limited to the GI tract.

PMID- 23125905
TI  - Antidiabetic treatment: Though lovers be lost, love shall not.
AB  - The new position statement of the American Diabetes Association and the European
      Association for the Study of Diabetes on the management of type 2 diabetes
      mellitus represents a paradigm shift in our understanding of antidiabetic
      treatment. It emphasises the necessity to individualise management based on
      patient needs. Glycaemic targets should also be pursued on an individualised
      basis. New therapeutic combinations are discussed, and the uncertainty
      surrounding the ideal choice is acknowledged. Above all, it is the mindful and
      experienced clinician who will implement the best available evidence towards
      flexible and efficacious treatment. Some areas of uncertainty may ensue, but it
      is expected that the new position statement will improve patient healthcare and
      treatment satisfaction. This now remains to be seen in practice.

PMID- 23125906
TI  - Efficacy and safety of vildagliptin in clinical practice-results of the PROVIL
      study.
AB  - AIM: To investigate efficacy and safety of vildagliptin compared to other oral
      antidiabetics in clinical practice in Germany. METHODS: In this prospective,
      open, observational study, patients with type 2 diabetes mellitus (T2DM)
      previously on oral monotherapy were selected by their treating physician to
      receive either vildagliptin add-on to metformin (cohort 1), vildagliptin +
      metformin single-pill combination (SPC) (cohort 2) or another dual combination
      therapy with oral antidiabetic drugs (OADs) (cohort 3). According to routine
      clinical practice, interim examinations occurred every 3 mo: at baseline, after
      approximately 3 mo and after approximately 6 mo. Parameters documented in the
      study included demographic and diagnostic data, history of T2DM, data on diabetes
      control, vital signs, relevant prior and concomitant medication and disease
      history. Efficacy was assessed by changes in HbA1c and fasting plasma glucose
      (FPG) 3 mo and 6 mo after initiation of dual combination therapy. Safety was
      assessed by adverse event reporting and measurement of specific laboratory values
      (serum creatinine, total bilirubin, alanine aminotransferase, aspartate
      aminotransferase, creatine kinase). RESULTS: Between October 2009 and January
      2011, a total of 3881 patients were enrolled in this study. Since 47 patients
      were withdrawn due to protocol violations, 3834 patients were included in the
      statistical analysis. There were no relevant differences between the three
      cohorts concerning age, body weight and body mass index. Average diabetes
      duration was approximately 6 years and mean HbA1c was between 7.6% and 7.9% at
      baseline. Antidiabetic treatment was recorded in 3648 patients. Patients were
      treated with vildagliptin add-on to metformin (n = 603), vildagliptin + metformin
      (SPC) (n = 2198), and other oral OADs including combinations of metformin with
      sulfonylurea (n = 370), with glitazones (n = 123), other dipeptidyl peptidase-4
      inhibitors (n = 99). After 6 mo of treatment, the absolute decrease in HbA1c
      (mean +/- SE) was significantly more pronounced in patients receiving
      vildagliptin add-on to metformin (-0.9% +/- 0.04%) and vildagliptin + metformin
      (SPC) (-0.9% +/- 0.03%) than in patients receiving other OADs (-0.6% +/- 0.04%; P
      < 0.0001). In addition, significant cohort differences were observed for the
      improvement in FPG after 6 mo treatment (vildagliptin add-on to metformin: -291
      mg/L +/- 18.3 mg/L; vildagliptin +metformin (SPC): -305 mg/L +/- 9.6 mg/L; other
      antidiabetic drugs: -209 mg/L +/- 14.0 mg/L for (P < 0.0001). Moderate decreases
      in body weight (absolute difference between last control and baseline: mean +/-
      SE) were observed for patients in all cohorts (vildagliptin add-on to metformin: 
      1.4 kg +/- 0.17 kg; vildagliptin + metformin (SPC): -1.7 kg +/- 0.09 kg; other
      OADs: -0.8 kg +/- 0.13 kg). No significant differences in adverse events (AEs)
      and other safety measures were observed between the cohorts. When performing an
      additional analysis by age (patients < 65 years vs patients >= 65 years), there
      was no relevant difference in the most common AEs between the two age groups and
      the AE profile was similar to that of the overall patient population. CONCLUSION:
      Clinical practice confirms that vildagliptin is an effective and well-tolerated
      treatment in combination with metformin in T2DM patients.

PMID- 23125907
TI  - Severe insulin resistance treatment with intravenous chromium in septic shock
      patient.
AB  - Insulin resistance has been well documented in critically ill patients. Adequate
      blood sugar control has been associated with better wound healing, and better
      outcomes in selected patient populations. Chromium is an essential component of
      human diet. It is believed to affect changes in glucose uptake. Several studies
      have shown beneficial effects of oral chromium in diabetic patients with insulin
      resistance, but role of intravenous chromium infusion has not been completely
      evaluated. We present a case of extreme insulin resistance in a 62-year-old woman
      with history of diabetes who suffered a cardiac arrest and respiratory failure,
      leading to aspiration pneumonia and septic shock requiring greater than 7000
      units of insulin over a period of 12 h which was successfully treated with
      intravenous chromium replacement.

PMID- 23125908
TI  - Characterization of the fungal microflora in raw milk and specialty cheeses of
      the province of Quebec.
AB  - The cheese microbial ecosystem is complex, and the presence of non-starter
      adventitious microorganisms in milk may have an influence on the organoleptic
      characteristics of cheese. The aim of this study was to analyze the composition
      and diversity of the fungal flora of raw milk destined for cheesemaking from 19
      dairy farms in Quebec and to monitor their evolution throughout ripening. Six
      hundred ten yeast and mold isolates were collected from raw milk and raw milk
      cheeses over a 9-month period. Based on the sequences of the rDNA ITS1-5.8S-ITS2
      region, 67% of the raw milk isolates were yeasts, which were assigned to 37
      species across 11 genera, while 33% were molds, which were assigned to 33 species
      across 25 genera. A semi-quantitative analysis of the yeasts and molds in the raw
      milk from four farms was performed over a 5-month period. The composition and
      diversity of the fungal microflora were totally different for each farm, each of
      which had a unique species profile. To determine whether adventitious yeast
      strains from the milk could develop in raw milk cheese, a multilocus-sequence
      typing (MLST) analysis was performed on 13 Issatchenkia orientalis (syn. Pichia
      kudriavzevii, anamorph: Candida krusei) isolates. The same MLST genotypes were
      identified for strains independently isolated from raw milk and raw milk cheese
      from a farm processing its own milk. This study contributes to the understanding
      of the natural fungal microflora of raw milk and suggests that non-starter yeasts
      and molds can transfer from raw milk to raw milk cheese and may influence cheese
      ripening. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article
      (doi:10.1007/s13594-011-0051-4) contains supplementary material, which is
      available to authorized users.

PMID- 23125910
TI  - Molecular breeding for the development of multiple disease resistance in Basmati
      rice.
AB  - BACKGROUND AND AIMS: Basmati rice grown in the Indian subcontinent is highly
      valued for its unique culinary qualities. Production is, however, often
      constrained by diseases such as bacterial blight (BB), blast and sheath blight
      (ShB). The present study developed Basmati rice with inbuilt resistance to BB,
      blast and ShB using molecular marker-assisted selection. METHODOLOGY: The rice
      cultivar 'Improved Pusa Basmati 1' (carrying the BB resistance genes xa13 and
      Xa21) was used as the recurrent parent and cultivar 'Tetep' (carrying the blast
      resistance gene Pi54 and ShB resistance quality trait loci (QTL), qSBR11-1) was
      the donor. Marker-assisted foreground selection was employed to identify plants
      possessing resistance alleles in the segregating generations along with stringent
      phenotypic selection for faster recovery of the recurrent parent genome (RPG) and
      phenome (RPP). Background analysis with molecular markers was used to estimate
      the recovery of RPG in improved lines. PRINCIPAL RESULTS: Foreground selection
      coupled with stringent phenotypic selection identified plants homozygous for
      xa13, Xa21 and Pi54, which were advanced to BC(2)F(5) through pedigree selection.
      Marker-assisted selection for qSBR11-1 in BC(2)F(5) using flanking markers
      identified seven homozygous families. Background analysis revealed that RPG
      recovery was up to 89.5%. Screening with highly virulent isolates of BB, blast
      and ShB showed that the improved lines were resistant to all three diseases and
      were on a par with 'Improved Pusa Basmati 1' for yield, duration and Basmati
      grain quality. CONCLUSIONS: This is the first report of marker-assisted transfer
      of genes conferring resistance to three different diseases in rice wherein genes
      xa13 and Xa21 for BB resistance, Pi54 for blast resistance, and a major QTL
      qSBR11-1 have been combined through marker-assisted backcross breeding. In
      addition to offering the potential for release as cultivars, the pyramided lines
      will serve as useful donors of gene(s) for BB, blast and ShB in future Basmati
      rice breeding programmes.

PMID- 23125909
TI  - The overlooked relationship between motivational abilities and posttraumatic
      stress: a review.
AB  - How does traumatic stress change the ability to motivate oneself to achieve
      certain goals? How do motivational abilities influence the development and course
      of trauma sequelae? Few studies have focused on motivational constructs within
      posttraumatic stress research. From a trauma research perspective, it can be
      hypothesized that traumatic stress may contribute to motivational dysfunction.
      The main goal of the present article is to fill this gap in research by reviewing
      and discussing the existing trauma literature in terms of motivation-related
      concepts, such as self-efficacy, locus of control, self-esteem, and self
      control/impulsivity. Fifty-four studies were reviewed, 10 of which were
      longitudinal studies. Approximately 20% of the reviews assessed whether
      motivational concepts predict posttraumatic stress, whereas only 8% examined the
      reverse relationship. With the exception of a few studies, motivational
      constructs seem to predict posttraumatic stress over the life span. The strongest
      relationships were reported for self-efficacy, followed by locus of control and
      self-esteem and, lastly, impulsivity/self-control. Overall, the findings of this
      review indicate that there is a lack of research investigating motivational
      factors as outcome variables following traumatic experiences. Furthermore, the
      need for longitudinal studies and studies with older adults is noted.

PMID- 23125911
TI  - Total Synthesis of Hyacinthacine A2: Stereocontrolled 5-aza-cyclooctene
      Photoisomerization and Transannular Hydroamination with Planar-to-Point Chirality
      Transfer.
AB  - The total synthesis of hyacinthacine A2 is reported via a novel transannular
      hydroamination in which planar chirality of a 5-aza-trans-cyclooctene precursor
      is transferred to point chirality in the product. Key to the success of this
      strategy was the development of a method for establishing absolute planar
      chirality via stereocontrolled photoisomerization of a 5-aza-cis-cyclooctene.
      This was accomplished by constructing a 5-aza-cis-cyclooctene precursor with a
      trans-fused acetonide. The improved diastereoselectivity observed upon
      photoisomerization of this derivative is attributed to the conformational strain
      of the eight-membered ring in the minor diastereomer.

PMID- 23125912
TI  - Rh(2)(S-PTTL)(3)TPA-A Mixed Ligand Dirhodium(II) Catalyst for Enantioselective
      Reactions of alpha-Alkyl-alpha-Diazoesters.
AB  - Herein we report the synthesis of the mixed ligand paddlewheel complex
      dirhodium(II) tris[N-phthaloyl-(S)-tert-leucinate] triphenylacetate, Rh(2)(S
      PTTL)(3)TPA, the structure of which bears similarity to the chiral crown complex
      Rh(2)(S-PTTL)(4). Rh(2)(S-PTTL)(3)TPA engages substrate classes (aliphatic
      alkynes, silylacetylenes, alpha-olefins) that are especially challenging in
      intermolecular reactions of alpha-alkyl-alpha-diazoesters, and catalyzes
      enantioselective cyclopropanation, cyclopropenation, and indole C-H
      functionalization with yields and enantioselectivities that are comparable or
      superior to Rh(2)(S-PTTL)(4). Mixing ligands on paddlewheel complexes offers a
      versatile handle for diversifying catalyst structure and reactivity. The results
      described herein illustrate how mixed ligand catalysts can create new
      opportunities for the optimization of catalytic asymmetric processes.

PMID- 23125913
TI  - Templated synthesis of nylon nucleic acids and characterization by nuclease
      digestion.
AB  - Nylon nucleic acids containing oligouridine nucleotides with pendent polyamide
      linkers and flanked by unmodified heteronucleotide sequences were prepared by DNA
      templated synthesis. Templation was more efficient than the single-stranded
      synthesis: Coupling step yields were as high as 99.2%, with up to 7 amide
      linkages formed in the synthesis of a molecule containing 8 modified nucleotides.
      Controlled digestion by calf spleen phosphodiesterase enabled the mapping of
      modified nucleotides in the sequences. A combination of complete degradation of
      nylon nucleic acids by snake venom phosphodiesterase and dephosphorylation of the
      resulting nucleotide fragments by bacterial alkaline phosphatase, followed by
      LCMS analysis, clarified the linear structure of the oligo-amide linkages. The
      templated synthesis strategy afforded nylon nucleic acids in the target structure
      and was compatible with the presence heteronucleotides. The complete digestion
      procedure produced a new species of DNA analogues, nylon ribonucleosides, which
      display nucleosides attached via a 2'-alkylthio linkage to each diamine and
      dicarboxylate repeat unit of the original nylon nucleic acids. The binding
      affinity of a nylon ribonucleoside octamer to the complementary DNA was evaluated
      by thermal denaturing experiments. The octamer was found to form stable duplexes
      with an inverse dependence on salt concentration, in contrast to the salt
      dependent DNA control.

PMID- 23125914
TI  - Conditional over-expression of PITX1 causes skeletal muscle dystrophy in mice.
AB  - Paired-like homeodomain transcription factor 1 (PITX1) was specifically up
      regulated in patients with facioscapulohumeral muscular dystrophy (FSHD) by
      comparing the genome-wide mRNA expression profiles of 12 neuromuscular disorders.
      In addition, it is the only known direct transcriptional target of the double
      homeobox protein 4 (DUX4) of which aberrant expression has been shown to be the
      cause of FSHD. To test the hypothesis that up-regulation of PITX1 contributes to
      the skeletal muscle atrophy seen in patients with FSHD, we generated a tet
      repressible muscle-specific Pitx1 transgenic mouse model in which expression of
      PITX1 in skeletal muscle can be controlled by oral administration of doxycycline.
      After PITX1 was over-expressed in the skeletal muscle for 5 weeks, the mice
      exhibited significant loss of body weight and muscle mass, decreased muscle
      strength, and reduction of muscle fiber diameters. Among the muscles examined,
      the tibialis anterior, gastrocnemius, quadricep, bicep, tricep and deltoid showed
      significant reduction of muscle mass, while the soleus, masseter and diaphragm
      muscles were not affected. The most prominent pathological change was the
      development of atrophic muscle fibers with mild necrosis and inflammatory
      infiltration. The affected myofibers stained heavily with NADH-TR with the
      strongest staining in angular-shaped atrophic fibers. Some of the atrophic fibers
      were also positive for embryonic myosin heavy chain using immunohistochemistry.
      Immunoblotting showed that the p53 was up-regulated in the muscles over
      expressing PITX1. The results suggest that the up-regulation of PITX1 followed by
      activation of p53-dependent pathways may play a major role in the muscle atrophy
      developed in the mouse model.

PMID- 23125915
TI  - Gene transfer of heme oxygenase-1 using an adeno-associated virus serotype 6
      vector prolongs cardiac allograft survival.
AB  - Introduction. Allograft survival can be prolonged by overexpression of
      cytoprotective genes such as heme oxygenase-1 (HO-1). Modifications in vector
      design and delivery have provided new opportunities to safely and effectively
      administer HO-1 into the heart prior to transplantation to improve long-term
      graft outcome. Methods. HO-1 was delivered to the donor heart using an adeno
      associated virus vector (AAV) with a pseudotype 6 capsid and vascular endothelial
      growth factor (VEGF) to enhance myocardial tropism and microvascular
      permeability. Survival of mouse cardiac allografts, fully or partially mismatched
      at the MHC, was determined with and without cyclosporine A. Intragraft cytokine
      gene expression was examined by PCR. Results. The use of AAV6 to deliver HO-1 to
      the donor heart, combined with immunosuppression, prolonged allograft survival by
      55.3% when donor and recipient were completely mismatched at the MHC and by 94.6%
      if partially mismatched. The combination of gene therapy and immunosuppression
      was more beneficial than treatment with either AAV6-HO-1 or CsA alone. IL-17a, b,
      e and f were induced in the heart at rejection. Conclusions. Pretreatment of
      cardiac allografts with AAV6-HO-1 plus cyclosporine A prolonged graft survival.
      HO-1 gene therapy represents a beneficial adjunct to immunosuppressive therapy in
      cardiac transplantation.

PMID- 23125916
TI  - Transcriptional Profile and Structural Conservation of SUMO-Specific Proteases in
      Schistosoma mansoni.
AB  - Small ubiquitin-related modifier (SUMO) is involved in numerous cellular
      processes including protein localization, transcription, and cell cycle control.
      SUMOylation is a dynamic process, catalyzed by three SUMO-specific enzymes and
      reversed by Sentrin/SUMO-specific proteases (SENPs). Here we report the
      characterization of these proteases in Schistosoma mansoni. Using in silico
      analysis, we identified two SENPs sequences, orthologs of mammalian SENP1 and
      SENP7, confirming their identities and conservation through phylogenetic
      analysis. In addition, the transcript levels of Smsenp1/7 in cercariae, adult
      worms, and in vitro cultivated schistosomula were measured by qRT-PCR. Our data
      revealed upregulation of the Smsenp1/7 transcripts in cercariae and early
      schistosomula, followed by a marked differential gene expression in the other
      analyzed stages. However, no significant difference in expression profile between
      the paralogs was observed for the analyzed stages. Furthermore, in order to
      detect deSUMOylating capabilities in crude parasite extracts, SmSENP1 enzymatic
      activity was evaluated using SUMO-1-AMC substrate. The endopeptidase activity
      related to SUMO-1 precursor processing did not differ significantly between
      cercariae and adult worms. Taken together, these results support the
      developmentally regulated expression of SUMO-specific proteases in S. mansoni.

PMID- 23125917
TI  - Schistosoma tegument proteins in vaccine and diagnosis development: an update.
AB  - The development of a vaccine against schistosomiasis and also the availability of
      a more sensitive diagnosis test are important tools to help chemotherapy in
      controlling disease transmission. Bioinformatics tools, together with the access
      to parasite genome, published recently, should help generate new knowledge on
      parasite biology and search for new vaccines or therapeutic targets and antigens
      to be used in the disease diagnosis. Parasite surface proteins, especially those
      expressed in schistosomula tegument, represent interesting targets to be used in
      vaccine formulations and in the diagnosis of early infections, since the tegument
      represents the interface between host and parasite and its molecules are
      responsible for essential functions to parasite survival. In this paper we will
      present the advances in the development of vaccines and diagnosis tests achieved
      with the use of the information from schistosome genome focused on parasite
      tegument as a source for antigens.

PMID- 23125918
TI  - Pathogenicity of Trichobilharzia spp. for Vertebrates.
AB  - Bird schistosomes, besides being responsible for bird schistosomiasis, are known
      as causative agents of cercarial dermatitis. Cercarial dermatitis develops after
      repeated contact with cercariae, mainly of the genus Trichobilharzia, and was
      described as a type I, immediate hypersensitivity response, followed by a late
      phase reaction. The immune response is Th2 polarized. Primary infection leads to
      an inflammatory reaction that is insufficient to eliminate the schistosomes and
      schistosomula may continue its migration through the body of avian as well as
      mammalian hosts. However, reinfections of experimental mice revealed an immune
      reaction leading to destruction of the majority of schistosomula in the skin.
      Infection with the nasal schistosome Trichobilharzia regenti probably represents
      a higher health risk than infections with visceral schistosomes. After the skin
      penetration by the cercariae, parasites migrate via the peripheral nerves, spinal
      cord to the brain, and terminate their life cycle in the nasal mucosa of
      waterfowl where they lay eggs. T. regenti can also get over skin barrier and
      migrate to CNS of experimental mice. During heavy infections, neuroinfections of
      both birds and mammals lead to the development of a cellular immune response and
      axonal damage in the vicinity of the schistosomulum. Such infections are manifest
      by neuromotor disorders.

PMID- 23125919
TI  - Production, Purification, and Characterization of Polygalacturonase from
      Rhizomucor pusillus Isolated from Decomposting Orange Peels.
AB  - A thermophilic fungal strain producing polygalacturonase was isolated after
      primary screening of 40 different isolates. The fungus was identified as
      Rhizomucor pusilis by Microbial Type Culture Collection (MTCC), Chandigarh,
      India. An extracellular polygalacturonase (PGase) from R. pusilis was purified to
      homogeneity by two chromatographic steps using Sephadex G-200 and Sephacryl S
      100. The purified enzyme was a monomer with a molecular weight of 32 kDa. The
      PGase was optimally active at 55 degrees C and at pH 5.0. It was stable up to 50
      degrees C for 120 min of incubation and pH condition between 4.0 and 5.0. The
      stability of PGase decreases rapidly above 60 degrees C and above pH 5.0. The
      apparent K(m) and V(max) values were 0.22 mg/mL and 4.34 U/mL, respectively. It
      was the first time that a polygalacturonase enzyme was purified in this species.
      It would be worthwhile to exploit this strain for polygalacturonase production.
      Polygalacturonase from this strain can be recommended for the commercial
      production because of its constitutive and less catabolically repressive nature,
      thermostability, wide range of pH, and lower K(m) properties. However, scale-up
      studies are needed for the better output for commercial production.

PMID- 23125920
TI  - Choosing between GLP-1 Receptor Agonists and DPP-4 Inhibitors: A Pharmacological
      Perspective.
AB  - In recent years the incretin therapies have provided a new treatment option for
      patients with type 2 diabetes mellitus (T2DM). The incretin therapies focus on
      the increasing levels of the two incretin hormones, glucagon-like peptide 1 (GLP
      1) and glucose-dependent insulinotropic polypeptide (GIP). This results in
      increased glucose dependent insulin synthesis and release. GLP-1 receptor
      agonists such as liraglutide and exenatide exert an intrinsic biological effect
      on GLP-1 receptors directly stimulating the release of insulin from pancreatic
      beta cells. DPP-4 inhibitors such as sitagliptin and linagliptin prevent the
      inactivation of endogenous GLP-1 and GIP through competitive inhibition of the
      DPP-4 enzyme. Both incretin therapies have good safety and tolerability profiles
      and interact minimally with a number of medications commonly prescribed in T2DM.
      This paper focuses on the pharmacological basis by which the incretin therapies
      function and how this knowledge can inform and benefit clinical decisions. Each
      individual incretin agent has benefits and pitfalls relating to aspects such as
      glycaemic and nonglycaemic efficacy, safety and tolerability, ease of
      administration, and cost. Overall, a personalized medicine approach has been
      found to be favourable, tailoring the incretin agent to benefit and suit
      patient's needs such as renal impairment (RI) or hepatic impairment (HI).

PMID- 23125921
TI  - The opposite effects of high-sucrose and high-fat diet on Fatty Acid oxidation
      and very low density lipoprotein secretion in rat model of metabolic syndrome.
AB  - Aims. To determine the effect of two different diets (high-sucrose (HS) and high
      fat (HF)) on the main metabolic pathways potentially contributing to the
      development of steatosis: (1) activity of the liver lysosomal and heparin
      releasable lipases; (2) fatty acid (FFA) oxidation; (3) FFA synthesis de novo;
      (4) VLDL output in vivo in a rat model of metabolic syndrome (MetS), hereditary
      hypertriglyceridemic (HHTg) rats fed HS or HF diets. Results. Both diets resulted
      in triacylglycerol (TAG) accumulation in the liver (HF > HS). The intracellular
      TAG lipolysis by lysosomal lipase was increased in both groups and positively
      correlated with the liver TAG content. Diet type significantly affected
      partitioning of intracellular TAG-derived fatty acids among FFA-utilizing
      metabolic pathways as HS feeding accentuated VLDL secretion and downregulated FFA
      oxidation while the HF diet had an entirely opposite effect. FFA de novo
      synthesis from glucose was significantly enhanced in the HS group (fed ? fasted)
      while being completely eradicated in the HF group. Conclusions. We found that in
      rats prone to the development of MetS associated diseases dietary-induced
      steatosis is not simply a result of impaired TAG degradation but that it depends
      on other mechanisms (elevated FFA synthesis or attenuated VLDL secretion) that
      are specific according to diet composition.

PMID- 23125922
TI  - Goal-directed therapy: new trends and horizons.

PMID- 23125923
TI  - Preparation and Support of Patients through the Transplant Process: Understanding
      the Recipients' Perspectives.
AB  - Preparation for heart transplant commonly includes booklets, instructional
      videos, personalized teaching sessions, and mentorship. This paper explores heart
      transplant recipients' thoughts on their preparation and support through the
      transplant process. Twenty-five interviews were audio-/videotaped capturing voice
      and body language and transcribed verbatim. Coding addressed language, bodily
      gesture, volume, and tone in keeping with our visual methodology. Recipients
      reported that only someone who had a transplant truly understands the experience.
      As participants face illness and life-altering experiences, maintaining a
      positive attitude and hope is essential to coping well. Healthcare professionals
      provide ongoing care and reassurance about recipients' medical status. Mentors,
      family members, and close friends play vital roles in supporting recipients.
      Participants reported that only heart transplant recipients understood the
      experience, the hope, and ultimately the suffering associated with living with
      another persons' heart. Attention needs to be focused not solely on the use of
      teaching modalities, but also on the development of innovative support networks.
      This will promote patient and caregiver engagement in self-management. Enhancing
      clinicians' knowledge of the existential aspects of transplantation will provide
      them with a nuanced understanding of the patients' experience, which will
      ultimately enhance their ability to better prepare and support patients and their
      caregivers.

PMID- 23125924
TI  - Minimally invasive cardiac surgery: transapical aortic valve replacement.
AB  - Minimally invasive cardiac surgery is less traumatic and therefore leads to
      quicker recovery. With the assistance of engineering technologies on devices,
      imaging, and robotics, in conjunction with surgical technique, minimally invasive
      cardiac surgery will improve clinical outcomes and expand the cohort of patients
      that can be treated. We used transapical aortic valve implantation as an example
      to demonstrate that minimally invasive cardiac surgery can be implemented with
      the integration of surgical techniques and engineering technologies. Feasibility
      studies and long-term evaluation results prove that transapical aortic valve
      implantation under MRI guidance is feasible and practical. We are investigating
      an MRI compatible robotic surgical system to further assist the surgeon to
      precisely deliver aortic valve prostheses via a transapical approach. Ex vivo
      experimentation results indicate that a robotic system can also be employed in in
      vivo models.

PMID- 23125925
TI  - The long-term effects of mandibular distraction osteogenesis on developing
      deciduous molar teeth.
AB  - Background. Many studies have demonstrated the effectiveness of mandibular
      distraction osteogenesis (MDO) in alleviating the micrognathia-associated upper
      airway obstruction but very few studies have focused on long-term dental
      outcomes. Objective. To report the effect of MDO on developing deciduous molars
      in the distraction area. Methods. A retrospective chart review was performed to
      identify patients with Pierre Robin sequence who underwent MDO with documented
      long-term dental assessments. Results. Ten children (mean age at surgery 69.8
      days; 6 boys and 4 girls) were included for analysis. All patients underwent
      bilateral MDO with an inverted L-shaped osteotomy to avoid injuring tooth buds.
      The dental developmental stage was primary dentition in all children. Overall, 3
      patients developed minor dental problems involving 4 molar teeth (2 root
      malformations and 2 shape anomalies) but they did not require any interventions.
      Conclusion. Significant primary molar developmental complications were not seen
      in our patients. The use of internal distractor device with an inverted L-shaped
      osteotomy seems to be a safe surgical approach in regards to dental outcomes.

PMID- 23125926
TI  - Lung radiofrequency ablation: potential as a therapy to oligometastasis and
      oligorecurrence.
AB  - The early results (e.g., patient survival) of RFA for the treatment of patients
      with NSCLC and pulmonary metastasis from various primary lesions including
      colorectal cancer, lung cancer, hepatocellular carcinoma, renal cell carcinoma,
      and sarcoma appear encouraging and suggest the potential to offer long-term
      survival for the patients with oligorecurrence or oligometastasis of lung cancer.
      The usefulness of RFA for oligorecurrence or oligometastasis of lung cancer
      should be clarified by prospective studies in the future.

PMID- 23125927
TI  - A call for the aggressive treatment of oligometastatic and oligo-recurrent non
      small cell lung cancer.
AB  - Metastatic non-small cell lung cancer (NSCLC) carries a dismal prognosis.
      Clinical evidence suggests the existence of an intermediate, or oligometastatic,
      state when metastases are limited in number and/or location. In addition,
      following initial curative therapy, many patients present with limited metastatic
      disease, or oligo-recurrence. Metastasis-directed, anti-cancer therapies may
      benefit these patients. A growing evidence-base supports the use of
      hypofractionated, image-guided radiotherapy (HIGRT) for a variety of malignant
      conditions including inoperable stage I NSCLC and many metastatic sites. When
      surgical resection is not possible, HIGRT offers an effective alternative for
      local treatment of limited metastatic disease. Early studies have produced
      promising results when HIGRT was delivered to all known sites of disease in
      patients with oligometastatic/oligo-recurrent NSCLC. In a population of patients
      formerly considered rapidly terminal, these studies report five year overall
      survival rates of 13-22%. HIGRT for metastatic NSCLC warrants further study. We
      call for large, intergroup, and even international randomized trials
      incorporating HIGRT and other metastasis-directed therapies into the treatment of
      patients with oligometastatic/oligo-recurrent NSCLC.

PMID- 23125928
TI  - Double Bolus Application in TWIST-MR-Angiography of the Cervical Arteries.
AB  - Purpose. The aim of the present work was to test the feasibility of the time
      resolved MR-angiography (TWIST-MRA) of cervical arteries using double bolus
      injection. Material and Methods. TWIST-MRA with a temporal resolution of 8.4
      seconds for each frame and a spatial resolution with a voxel size of 0.61 * 0.58
      * 0.8 mm(3) was performed in 24 patients. A biphasic bolus injection protocol was
      used with the second injection being started 21 seconds after the first contrast
      dye bolus. Diagnostic image quality was rated according to a 4-point scale.
      Results. In 12 patients (50%) no clear separation between the cervical venous and
      arterial vessels was evident after the first bolus injection. Using TWIST-MRA
      data acquired after the second bolus a sufficient diagnostic image quality
      (rating >=3, mean 3.5) could be obtained in 22 of 24 patients (92%). Discussion.
      The double bolus injection protocol using TWIST-MRA allows for very good
      separation of the cervical arteries.

PMID- 23125929
TI  - Entrapment neuropathies in the upper and lower limbs: anatomy and MRI features.
AB  - Peripheral nerve entrapment occurs at specific anatomic locations. Familiarity
      with the anatomy and the magnetic resonance imaging (MRI) features of nerve
      entrapment syndromes is important for accurate diagnosis and early treatment of
      entrapment neuropathies. The purpose of this paper is to illustrate the normal
      anatomy of peripheral nerves in the upper and lower limbs and to review the MRI
      features of common disorders affecting the peripheral nerves, both
      compressive/entrapment and noncompressive, involving the suprascapular nerve, the
      axillary nerve, the radial nerve, the ulnar nerve, and the median verve in the
      upper limb and the sciatic nerve, the common peroneal nerve, the tibial nerve,
      and the interdigital nerves in the lower limb.

PMID- 23125930
TI  - Jumping to conclusions is associated with paranoia but not general
      suspiciousness: a comparison of two versions of the probabilistic reasoning
      paradigm.
AB  - Theoretical models ascribe jumping to conclusions (JTCs) a prominent role in the
      pathogenesis of paranoia. While many earlier studies corroborated this account,
      some newer investigations have found no or only small associations of the JTC
      bias with paranoid symptoms. The present study examined whether these
      inconsistencies in part reflect methodological differences across studies. The
      study was built upon the psychometric high-risk paradigm. A total of 1899
      subjects from the general population took part in an online survey and were
      administered the Paranoia Checklist as well as one of two different variants of
      the probabilistic reasoning task: one variant with a traditional instruction (a)
      and one novel variant that combines probability estimates with decision judgments
      (b). Factor analysis of the Paranoia Checklist yielded an unspecific
      suspiciousness factor and a psychotic paranoia factor. The latter was
      significantly associated with scores indicating hasty decision making. Subjects
      scoring two standard deviations above the mean of the Paranoia Checklist showed
      an abnormal data-gathering style relative to subjects with normal scores.
      Findings suggest that the so-called decision threshold parameter is more
      sensitive than the conventional JTC index. For future research the specific
      contents of paranoid beliefs deserve more consideration in the investigation of
      decision making in schizophrenia as JTC seems to be associated with core
      psychosis-prone features of paranoia only.

PMID- 23125931
TI  - Is there successful aging for nonagenarians? The vitality 90+ study.
AB  - Objectives. This study was designed (1) to estimate the prevalence of successful
      aging among nonagenarians based on six different models and (2) to investigate
      whether successful aging is associated with socio-demographic factors. Methods. A
      mailed survey was conducted with people aged 90+ in Tampere in 2010. Responses
      were received from 1283 people. The prevalence of successful aging was measured
      by six multidimensional models including physical, social, and psychological
      components. Age, sex, marital status, level of education, and place of living
      were studied as factors associated with successful aging. Results. The prevalence
      of successful aging varied from 1.6% to 18.3% depending on the model applied.
      Successful aging was more prevalent in men, and also more prevalent among
      community-living people. In most models, successful aging was also associated
      with younger age, being married, and a higher level of education. Discussion.
      Models which emphasize the absence of disease and activity as criteria for
      successful aging may not be the most relevant and applicable in oldest old.
      Instead, preference should be given to models that focus more on autonomy,
      adaptation and sense of purpose. Age-sensitive approaches would help us better
      understand the potential of successful aging among individuals who already have
      success in longevity.

PMID- 23125932
TI  - Induced brain plasticity after a facilitation programme for autobiographical
      memory in multiple sclerosis: a preliminary study.
AB  - This preliminary study tackles the assessment and treatment of autobiographical
      memory (AbM) in relapsing-remitting multiple sclerosis (RR-MS) patients. Our aim
      was to investigate cerebral activation changes, following clinical improvement of
      AbM due to a cognitive training based on mental visual imagery (MVI). We assessed
      AbM using the Autobiographical Interview (AI) in eight patients and 15 controls.
      The latter subjects established normative data. The eight patients showed
      selective defective performance on the AI. Four patients were trained cognitively
      and underwent pre- and post-AI and fMRI. The remaining four patients took a
      second AI, at the same interval, but with no intervention in between. Results
      showed a significant improvement of AbM performance after the facilitation
      programme that could not be explained by learning effects since the AI scores
      remained stable between the two assessments in the second group of patients. As
      expected, AbM improvement was accompanied by an increased cerebral activity in
      posterior cerebral regions in post-facilitation fMRI examination. We interpret
      this activation changes in terms of reflecting the emphasis made on the role of
      MVI in memory retrieval through the facilitation programme. These preliminary
      significant clinical and neuroimaging changes suggest the beneficial effects of
      this technique to alleviate AbM retrieval deficit in MS patients.

PMID- 23125933
TI  - Multiple roles for VEGF in non-melanoma skin cancer: angiogenesis and beyond.
AB  - Vascular endothelial growth factor (VEGF) is known to play a critical role in the
      development of non-melanoma skin cancers. VEGF is a potent pro-angiogenic factor
      and it is elevated in mouse and human skin tumors. The use of transgenic and
      knockout mice has shown that VEGF is essential for tumor development in multiple
      models of skin carcinogenesis and, until recently, the mechanism of action has
      been primarily attributed to the induction of angiogenesis. However, additional
      roles for VEGF have now been discovered. Keratinocytes can respond directly to
      VEGF, which could influence skin carcinogenesis by altering proliferation,
      survival, and stemness. In vivo studies have shown that loss of epidermal VEGFR-1
      or neuropillin-1 inhibits carcinogenesis, indicating that VEGF can directly
      affect tumor cells. Additionally, VEGF has been shown to promote tumor growth by
      recruiting macrophages to skin tumors, which likely occurs through VEGFR-1.
      Overall, these new studies show that VEGF carries out functions beyond its well
      established effects on angiogenesis and highlight the need to consider these
      alternative activities when developing new treatments for non-melanoma skin
      cancer.

PMID- 23125934
TI  - Diagnostic role of chromosomal instability in melanoma.
AB  - Early diagnosis gives melanoma patients the best chance for long term survival.
      However discrimination of an early melanoma from an unusual/atypical benign nevus
      can represent a significant challenge. There are no current pathological markers
      to definitively define malignant potential in these indeterminate lesions. Thus,
      there is a need for improved diagnostic tools. Chromosomal instability (CIN) is a
      hallmark of cancer and is markedly prevalent in melanoma. Advances in genomics
      have opened the door for the development of molecular tools to better segregate
      benign and malignant lesions. This paper focuses on CIN in melanoma and the role
      of current diagnostic approaches.

PMID- 23125935
TI  - A New Generation Microarray for the Simultaneous Detection and Identification of
      Yersinia pestis and Bacillus anthracis in Food.
AB  - The use of microarrays as a multiple analytic system has generated increased
      interest and provided a powerful analytical tool for the simultaneous detection
      of pathogens in a single experiment. A wide array of applications for this
      technology has been reported. A low density oligonucleotide microarray was
      generated from the genetic sequences of Y. pestis and B. anthracis and used to
      fabricate a microarray chip. The new generation chip, consisting of 2,240 spots
      in 4 quadrants with the capability of stripping/rehybridization, was designated
      as "Y-PESTIS/B-ANTHRACIS 4x2K Array." The chip was tested for specificity using
      DNA from a panel of bacteria that may be potentially present in food. In all, 37
      unique Y. pestis-specific and 83 B. anthracis-specific probes were identified.
      The microarray assay distinguished Y. pestis and B. anthracis from the other
      bacterial species tested and correctly identified the Y. pestis-specific
      oligonucleotide probes using DNA extracted from experimentally inoculated milk
      samples. Using a whole genome amplification method, the assay was able to detect
      as low as 1 ng genomic DNA as the start sample. The results suggest that
      oligonucleotide microarray can specifically detect and identify Y. pestis and B.
      anthracis and may be a potentially useful diagnostic tool for detecting and
      confirming the organisms in food during a bioterrorism event.

PMID- 23125936
TI  - Periarticular injection with bupivacaine for postoperative pain control in total
      knee replacement: a prospective randomized double-blind controlled trial.
AB  - Background. Local periarticular injection with bupivacaine alone in TKA has not
      been studied. Thus, we aimed to examine the effectiveness of local periarticular
      injection with bupivacaine for post-operative pain control in TKA. Method. Sixty
      patients undergoing TKA by a single surgeon were randomly assigned into two
      groups in a double-blind, placebo-controlled study. In the injection group,
      patients received periarticular injections with 0.25% bupivacaine before wound
      closure; in the control group, patients received a 0.9% normal saline injection.
      Both groups received the same anesthetic procedure, post-operative pain control,
      and rehabilitation protocol. Results. There was a significant reduction in post
      operative morphine consumption in the first six hours after the operation (mean
      0.9 mg and 2.43 mg, P = 0.01), but there was no significant difference in post
      operative morphine consumption between six hours and ninety-six hours after the
      operation, visual analogue scale (VAS) score, morphine side effects during the
      first 96 hours, length of hospital stay, or complications from morphine
      consumption. Conclusion. Local periarticular injection with bupivacaine alone
      before wound closer was shown to be an effective method to improve pain control
      after TKA with a few complications and ease of use.

PMID- 23125938
TI  - Radix entomolaris in mandibular first molars in Indian population: a review and
      case reports.
AB  - Purpose. The aim of this paper is to present cases of mandibular first molars
      with an additional distolingual root and their management using appropriate
      instruments and techniques. Basic Procedures and Main Findings. Mandibular molars
      can sometimes present a variation called radix entomolaris, wherein the tooth has
      an extra root attached to its lingual aspect. This additional root may complicate
      the endodontic management of the tooth if it is misdiagnosed or maltreated. This
      paper reviews the prevalence of such cases in Indian population and reports the
      management of 6 such teeth. Principal Conclusions. (1) It is crucial to be
      familiar with variations in tooth/canal anatomy and characteristic features since
      such knowledge can aid location and negotiation of canals, as well as their
      subsequent management. (2) Accurate diagnosis and careful application of clinical
      endodontic skill can favorably alter the prognosis of mandibular molars with this
      root morphology.

PMID- 23125939
TI  - Primary oral myiasis: a case report.
AB  - Myiasis commonly refers to invasion of live human or animal tissue by fly larvae
      of the Diptera order where they complete their cycle totally or in part, feeding
      on living or dead tissue, as well as on body fluids. Infestation of tissues of
      vertebrate species is pandemic but more frequently found in tropical and
      subtropical countries where poor hygiene, poor housing infrastructure, warm humid
      climate, and proximity with domestic animals prevail. Its diagnosis is made
      basically by the presence of larvae. The present paper reports a case of gingival
      myiasis involving 14-16 larvae in a 12-year-old boy.

PMID- 23125937
TI  - The adaptive neuroplasticity hypothesis of behavioral maintenance.
AB  - Physical activity is a seemingly simple and clinically potent method to decrease
      morbidity and mortality in people with coronary heart disease (CHD). Nonetheless,
      long-term maintenance of physical activity remains a frustratingly elusive goal
      for patients and practitioners alike. In this paper, we posit that among older
      adults with CHD, recidivism after the initiation of physical activity reflects
      maladaptive neuroplasticity of malleable neural networks, and people will revert
      back to learned and habitual physical inactivity patterns, particularly in the
      setting of stress or depression. We hypothesize that behavioral interventions
      that successfully promote physical activity may also enhance adaptive
      neuroplasticity and play a key role in the maintenance of physical activity
      through the development of new neuronal pathways that enhance functional ability
      in older adults. Conversely, without such adaptive neuroplastic changes,
      ingrained maladaptive neuroplasticity will prevail and long-term maintenance of
      physical activity will fail. In this paper we will: (1) describe the enormous
      potential for neuroplasticity in older adults; (2) review stress and depression
      as examples of maladaptive neuroplasticity; (3) describe an example of adaptive
      neuroplasticity achieved with a behavioral intervention that induced positive
      affect in people with CHD; and (4) discuss implications for future work in bench
      to bedside translational research.

PMID- 23125940
TI  - Laparoscopic splenectomy for splenic hamartoma: a case report.
AB  - Hamartoma is a rare splenic benign tumor usually accidentally detected as a
      radiologic finding. Preoperative diagnosis poses a challenge and thus surgery
      becomes necessary to confirm the clinical suspicion. Laparoscopic splenectomy has
      gained consensus as a standard surgical procedure particularly for autoimmune
      hematological diseases. This former experience has allowed this technique to be
      extended to other splenic pathologies. Here we report a case of total
      laparoscopic splenectomy for a bulky splenic hamartoma in a young male patient.

PMID- 23125941
TI  - Parkinson's disease and autophagy.
AB  - It is generally accepted that a correlation between neurodegenerative disease and
      protein aggregation in the brain exists; however, a causal relationship has not
      been elucidated. In neurons, failure of autophagy may result in the accumulation
      of aggregate-prone proteins and subsequent neurodegeneration. Thus,
      pharmacological induction of autophagy to enhance the clearance of
      intracytoplasmic aggregate-prone proteins has been considered as a therapeutic
      strategy to ameliorate pathology in cell and animal models of neurodegenerative
      disorders. However, autophagy has also been found to be a factor in the onset of
      these diseases, which raises the question of whether autophagy induction is an
      effective therapeutic strategy, or, on the contrary, can result in cell death. In
      this paper, we will first describe the autophagic machinery, and we will consider
      the literature to discuss the neuroprotective effects of autophagy.

PMID- 23125943
TI  - Determining the Feasibility of Ambulance-Based Randomised Controlled Trials in
      Patients with Ultra-Acute Stroke: Study Protocol for the "Rapid Intervention with
      GTN in Hypertensive Stroke Trial" (RIGHT, ISRCTN66434824).
AB  - Background. Time from acute stroke to enrolment in clinical trials needs to be
      reduced to improve the chances of finding effective treatments. No completed
      randomised controlled trials of ambulance-based treatment for acute stroke have
      been reported in the UK, and the practicalities of recruiting, consenting, and
      treating patients are unknown. Methods. RIGHT is an ambulance based, single
      blind, randomised controlled trial with blinded-outcome assessment. The trial
      will assess feasibility of using ambulance services to deliver ultra-acute stroke
      treatments; a secondary aim is to assess the effect of glyceryl trinitrate (GTN)
      on haemodynamic variables and functional outcomes. Initial consent,
      randomisation, and treatment are performed by paramedics prior to
      hospitalisation. Patients with ultra-acute stroke (<=4 hours of onset) are
      randomised to transdermal GTN (5 mg/24 hours) or gauze dressing daily for 7 days.
      The primary outcome is systolic blood pressure at 2 hours. Secondary outcomes
      include feasibility, haemodynamics, dependency, and other functional outcomes. A
      nested qualitative study is included. Trial Status. The trial has all relevant
      ethics and regulatory approvals and recruitment started on February 15, 2010. The
      trial stopped recruitment in December 2011 after 41 patients were recruited.
      Trial Registration. The trial registration number is ISRCTN66434824 and EudraCT
      number is 2007-004766-40.

PMID- 23125944
TI  - Assessing Chemical Mixtures and Human Health: Use of Bayesian Belief Net
      Analysis.
AB  - BACKGROUND: Despite humans being exposed to complex chemical mixtures, much of
      the available research continues to focus on a single compound or metabolite or a
      select subgroup of compounds inconsistent with the nature of human exposure.
      Uncertainty regarding how best to model chemical mixtures coupled with few
      analytic approaches remains a formidable challenge and served as the impetus for
      study.  OBJECTIVES: To identify the polychlorinated biphenyl (PCB) congener(s)
      within a chemical mixture that was most associated with an endometriosis
      diagnosis using novel graphical modeling techniques.  METHODS: Bayesian Belief
      Network (BBN) models were developed and empirically assessed in a cohort
      comprising 84 women aged 18-40 years who underwent a laparoscopy or laparotomy
      between 1999 and 2000; 79 (94%) women had serum concentrations for 68 PCB
      congeners quantified. Adjusted odds ratios (AOR) for endometriosis were estimated
      for individual PCB congeners using BBN models.  RESULTS: PCB congeners #114 (AOR
      = 3.01; 95% CI = 2.25, 3.77) and #136 (AOR = 1.79; 95% CI = 1.03, 2.55) were
      associated with an endometriosis diagnosis. Combinations of mixtures inclusive of
      PCB #114 were all associated with higher odds of endometriosis, underscoring its
      potential relation with endometriosis.  CONCLUSIONS: BBN models identified PCB
      congener 114 as the most influential congener for the odds of an endometriosis
      diagnosis in the context of a 68 congener chemical mixture. BBN models offer
      investigators the opportunity to assess which compounds within a mixture may
      drive a human health effect.

PMID- 23125942
TI  - Clinical features, pathophysiology, and treatment of levodopa-induced dyskinesias
      in Parkinson's disease.
AB  - Dyskinetic disorders are characterized by excess of motor activity that may
      interfere with normal movement control. In patients with Parkinson's disease, the
      chronic levodopa treatment induces dyskinetic movements known as levodopa-induced
      dyskinesias (LID). This paper analyzed the pathophysiology, clinical
      manifestations, pharmacological treatments, and surgical procedures to treat
      hyperkinetic disorders. Surgery is currently the only treatment available for
      Parkinson's disease that may improve both parkinsonian motor syndrome and LID.
      However, this paper shows the different mechanisms involved are not well
      understood.

PMID- 23125945
TI  - Suppression of Nitric Oxide Production and Cardiovascular Risk Factors in Healthy
      Seniors and Hypercholesterolemic Subjects by a Combination of Polyphenols and
      Vitamins.
AB  - BACKGROUND: Dysregulated immune function associated with ageing has been
      implicated in a variety of human diseases. We have demonstrated the anti
      inflammatory properties of resveratrol, pterostilbene, morin hydrate, quercetin,
      delta-tocotrienol, riboflavinin a variety of experimental animal models, and
      determined that these compounds act by inhibiting proteasome activity.  AIMS: To
      determine whether serum nitric oxide (NO) levels increase with age in humans, and
      whether the combined cholesterol-lowering and inflammation-reducing properties of
      resveratrol, pterostilbene, Morin hydrate, quercetin, delta-tocotrienol,
      riboflavin, and nicotinic acid would reduce cardiovascular risk factors in humans
      when used as nutritional supplements with, or without, other dietary changes. 
      METHODS: Elderly human subjects were stratified into two groups based on total
      serum cholesterol levels. Initial total serum cholesterol levels were normal and
      elevated in Group 1 and 2 subjects, respectively. Baseline serum NO, C-reactive
      protein (CRP), gamma-glutamyltransferase (gamma-GT) activity, uric acid, total
      antioxidant status (TAS), total cholesterol, HDL-cholesterol, LDL-cholesterol,
      and triglycerides levels were established over a four week period. Group 1
      subjects subsequently received nutritional supplementation with one of two
      different combinations (NS-7 = 25 mg of each, resveratrol, pterostilbene,
      quercetin, delta-tocotrienol, nicotinic acid, morin hydrate or NS-6 = morin
      hydrate replaced with quercetin, 50 mg/capsule). Group 2 subjects also received
      these nutritional supplements (two capsules/d), but an AHA Step-1 diet was also
      implemented. After these interventions were administered for four weeks, the
      above parameters were re-measured and changes from baseline levels determined.
      Nitric acid (NO) levels in children, young adults, and seniors were also
      compared.  RESULTS: The key results of the current study were: 1) that serum NO
      levels were significantly increased in seniors compared to both children (~80%)
      and young adults (~65%); 2) that the intake of two capsules/d of NS-7 or NS-6 for
      four weeks significantly (P < 0.05) decreased serum NO (39%, 24%), CRP (19%,
      21%), uric acid (6%, 12%) levels, and gamma-GT activity (8%, 6%), respectively in
      free-living healthy seniors; 3) that serum NO (36%, 29%), CRP (29%, 20%), uric
      acid (6%, 9%) gamma-GT activity (9%, 18%), total cholesterol (8%, 11%), LDL
      cholesterol (10%, 13%), and triglycerides (16%, 23%) levels were significantly (P
      < 0.02) decreased in hypercholesterolemic subjects restricted to AHA Step-1 diet
      plus intake of SN-7 or SN-6 (two capsules/d), respectively; 4) that TAS was
      increased (3%, 9%; P < 0.05) in free-living healthy seniors receiving NS-7 or NS
      6 alone, and in hypercholesterolemic subjects plus AHA Step-1 diet (20%, 12%; P <
      0.02) with either of the combinations tested.  CONCLUSIONS: Serum NO levels are
      elevated in elderly humans compared to children or young adults. Diet
      supplementation with combinations of resveratrol, pterostilbene, morin hydrate,
      quercetin, delta-tocotrienol, riboflavin, and nicotinic acid reduce
      cardiovascular risk factors in humans when used as nutritional supplements with,
      or without, other dietary changes.

PMID- 23125948
TI  - A note from the Editor-in-Chief.

PMID- 23125946
TI  - Japanese Encephalitis Vaccines.
AB  - Japanese encephalitis (JE) is a significant human health concern in Asia,
      Indonesia and parts of Australia with more than 3 billion people potentially at
      risk of infection with Japanese encephalitis virus (JEV), the causative agent of
      JE. Given the risk to human health and the theoretical potential for JEV use as a
      bioweapon, the development of safe and effective vaccines to prevent JEV
      infection is vital for preserving human health. The development of vaccines for
      JE began in the 1940s with formalin-inactivated mouse brain-derived vaccines.
      These vaccines have been shown to induce a protective immune response and to be
      very effective. Mouse brain-derived vaccines were still in use until May 2011
      when the last lots of the BIKEN((r)) JE-VAX((r)) expired. Development of modern
      JE vaccines utilizes cell culture-derived viruses and improvements in
      manufacturing processes as well as removal of potential allergens or toxins have
      significantly improved vaccine safety. China has developed a live-attenuated
      vaccine that has proven to induce protective immunity following a single
      inoculation. In addition, a chimeric vaccine virus incorporating the prM and E
      structural proteins derived from the live-attenuated JE vaccine into the live
      attenuated yellow fever 17D vaccine virus backbone is currently in clinical
      trials. In this article, we provide a summary of JE vaccine development and on
      going clinical trials. We also discuss the potential risk of JEV as a bioweapon
      with a focus on virus sustainability if used as a weapon.

PMID- 23125947
TI  - Genetically Engineered Mesenchymal Stem Cells Influence Gene Expression in Donor
      Cardiomyocytes and the Recipient Heart.
AB  - AIMS: Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) or mesenchymal
      stem cells (MSCs) facilitate post-infarct recovery, but the potential benefit of
      combination therapy using MSCs and hESC-CMs has not been examined. Our objective
      was to define the gene expression changes in donor and host-derived cells that
      are induced in vivo after co-transplantation of cardiomyocytes with and without
      mesenchymal stem cells expressing the prosurvival gene heme oxygenase 1.  METHODS
      AND RESULTS: Human MSCs were engineered to over-express heme oxygenase-1 (HO-1)
      following lentiviral vector-mediated transduction. Athymic nude rats were
      subjected to myocardial infarction and received hESC-CMs alone, hESC-CMs plus
      human MSCs, hESC-CMs plus MSCs overexpressing HO-1, or saline. Real time PCR
      identified gene expression changes. Cardiac function was assessed by angiography.
      Co-transplantation of unmodified MSCs plus hESC-CMs elevated CXCR4, HGF, and IGF
      expression over levels induced by injection of hESC-derived cardiomyocytes alone.
      In animals co-transplanted with MSC over-expressing HO-1, the expression of these
      genes was further elevated. Gene expression levels of VEGF, TGF-beta, CCL2,
      SMAD7, STAT3 and cardiomyocyte transcription factors were highest in the HO-1 MSC
      plus hESC-CM group at 30 days. Human CD31+, CD34+, isl-1+, NXK2.5 and c-kit+
      transcripts were elevated. Rodent genes encoding NKX2.5, troponin T and CD31 were
      elevated and cell cycle genes were induced. Ejection fraction improved by six to
      seven percent.  CONCLUSIONS: Co-administration of HO-1 MSCs plus hESC-CMs
      increased expression of pro-survival and angiogenesis-promoting genes in human
      cells and transcripts of cardiac and endothelial cell markers in rodent cells,
      consistent with activation of tissue repair in both transplanted hESC-CMs and the
      host heart.

PMID- 23125949
TI  - The PAKs come of age: Celebrating 18 years of discovery.
AB  - Protein kinases are versatile signaling molecules that are involved in the
      regulation most physiological responses. The p21-activated kinases (PAKs) can be
      activated directly by the small GTPases Rac and Cdc42 and are among the best
      characterized downstream effectors of these Rho proteins. The structure,
      substrate specificity and functional role of PAKS are evolutionarily conserved
      from protozoa to mammals. Vertebrate PAKs are particularly important for
      cytoskeletal remodeling and focal adhesion assembly, thereby contributing to
      dynamic processes such as cell migration and synaptic plasticity. This issue of
      Cellular Logistics focuses on the PAK family of kinases, with ten reviews written
      by researchers currently working in the field. Here in this introductory overview
      we highlight some of the most interesting recent discoveries regarding PAK
      biochemistry and biology. The reviews in this issue cover a range of topics
      including the atomic structures of PAK1 and PAK4, their role in animals as
      assessed by knockout studies, and how PAKs are likely to contribute to cancer and
      neurodegenerative diseases. The promise remains that PAK inhibitors will emerge
      that validate current pre-clinical studies suggesting that blocking PAK activity
      will positively contribute to human health.

PMID- 23125950
TI  - Untangling the complexity of PAK1 dynamics: The future challenge.
AB  - PAK1 kinase is a crucial regulator of a variety of cellular processes, such as
      motility, cell division, gene transcription and apoptosis. Its deregulation is
      involved in several pathologies, including cancer, viral infection and
      neurodegenerative diseases. Due to this strong implication in human health, the
      complex network of signaling pathways centered on PAK1 is a subject of intensive
      investigations. This review summarizes the present knowledge on the multiple PAK1
      intracellular localizations and on its shuttling between different compartments.
      The dynamics of PAK1 localization and activation are finely tuned by the cell and
      it is this tight control that underlies the capacity of PAK1 to participate in
      the regulation of many fundamental cell functions. Recently, PAK1 biosensors have
      been developed to visualize PAK1 activation in live cells. These new imaging
      tools should be of great help to better understand PAK1 biology and to conceive
      strategies for efficient and specific PAK1 inhibitors.

PMID- 23125951
TI  - PAK4-6 in cancer and neuronal development.
AB  - PAKs 4, 5 and 6 are members of the group B family of p21-activated kinases. Among
      this group, PAK4 has been most extensively studied. While it has essential roles
      in embryonic development, in adults high levels of PAK4 are frequently associated
      with cancer. PAK4 is overexpressed in a variety of cancers, and the Pak4 gene is
      amplified in some cancers. PAK4 overexpression is sufficient to cause oncogenic
      transformation in cells and in mouse models. The tight connection between PAK4
      and cancer make it a promising diagnostic tool as well as a potential drug
      target. The group B PAKs also have important developmental functions. PAK4 is
      important for many early developmental processes, while PAK5 and PAK6 play roles
      in learning and memory in mice. This chapter provides an overview of the roles of
      the group B PAKs in cancer as well as development, and includes a discussion of
      PAK mediated signaling pathways and cellular functions.

PMID- 23125952
TI  - PAK in pathogen-host interactions.
AB  - Eukaryotic, prokaryotic and viral pathogens are known to interfere with signaling
      pathways of their host to promote their own survival and proliferation. Here, we
      present selected examples of modulation of PAK activity in human cells by both
      intracellular and extracellular pathogens, focusing on one eukaryotic pathogen,
      the human malaria parasite Plasmodium falciparum, two Gram-negative bacteria
      (Helicobacter pylori and Pseudomonas aeruginosa), and two viruses belonging to
      distinct groups, the lentivirus HIV and the orthomyxovirus Influenza virus A.

PMID- 23125953
TI  - A challenging empirical question: What are the effects of media on psychogenic
      illness during a community crisis?
AB  - Psychogenic illness during disasters can cripple emergency healthcare services.
      Almost all research into this phenomenon has been retrospective and
      observational, and much of it suggests that media coverage can amplify
      psychogenic outbreaks. But there is little empirical evidence that this is true
      or that, conversely, media reports can mitigate psychogenic symptoms. In their
      work experimentally inducing psychogenic illness, the authors became sharply
      aware that it is difficult to experimentally mimic real-time media coverage. Yet
      clarifying media's effects on psychogenic illness is important if we want to
      prevent psychological disturbance. To meet this challenge, the authors advocate
      the funding and development of research protocols in advance of public
      emergencies, ready to be implemented in real-time. Coupled with digital media,
      which can track the reading and viewing behavior of millions of people, this
      approach can help us better understand media's impact on public health during an
      emergency, for better or for worse.

PMID- 23125954
TI  - Connective Tissue Disease-associated Interstitial Lung Disease: A review.
AB  - Interstitial lung disease (ILD) is commonly encountered in patients with
      connective tissue diseases (CTD). Besides the lung parenchyma, the airways,
      pulmonary vasculature and structures of the chest wall may all be involved,
      depending on the type of CTD. As a result of this so-called multi-compartment
      involvement, airflow limitation, pulmonary hypertension, vasculitis and
      extrapulmonary restriction can occur alongside fibro-inflammatory parenchymal
      abnormalities in CTD. Rheumatoid arthritis (RA), systemic sclerosis (SSc), poly
      /dermatomyositis (PM/DM), Sjogren's syndrome (SjS), systemic lupus erythematosus
      (SLE), and undifferentiated (UCTD) as well as mixed connective tissue disease
      (MCTD) can all be associated with the development of ILD. Non-specific
      interstitial pneumonia (NSIP) is the most commonly observed histopathological
      pattern in CTD-ILD, but other patterns including usual interstitial pneumonia
      (UIP), organizing pneumonia (OP), diffuse alveolar damage (DAD) and lymphocytic
      interstitial pneumonia (LIP) may occur. Although the majority of patients with
      CTD-ILD experience stable or slowly advancing ILD, a small yet significant group
      exhibits a more severe and progressive course. Randomized placebo-controlled
      trials evaluating the efficacy of immunomodulatory treatments have been conducted
      only in SSc-associated ILD. However, clinical experience suggests that a handful
      of immunosuppressive medications are potentially effective in a sizeable portion
      of patients with ILD caused by other CTDs. In this manuscript, we review the
      clinical characteristics and management of the most common CTD-ILDs.

PMID- 23125955
TI  - Lifestyle Modification with Diet and Exercise in Obese Patients with Heart
      Failure - A Pilot Study.
AB  - OBJECTIVE: There is a paucity of data regarding intentional weight loss in obese
      heart failure patients. This study sought to ascertain the safety and
      effectiveness of a lifestyle modification program in patients with systolic heart
      failure and metabolic syndrome.  METHODS: Patients (n=20) with systolic heart
      failure (ejection fraction < 50%) and metabolic syndrome were randomized to
      standard medical therapy (Control) versus medical therapy and lifestyle
      modification (Lifestyle) and followed prospectively for 3 months. Lifestyle
      modification involved a walking program and reduced calorie diet with 2 meal
      replacement products (Slim Fast(r)) daily. Patients attended weekly meetings with
      a dietitian for 12 weeks. Endpoints were obtained at baseline and 3 months and
      included physical exam, laboratory values, quality of life questionnaire, 6
      minute walk, and brachial ultrasound.  RESULTS: At 3 months, 5 patients in each
      group had lost weight. Excluding 1 patient in each group who had increased
      diuretic dosing, the overall change in weight was -0.84 +/- 3.82 and -0.50 +/-
      3.64 kg (p=0.85) in the control versus lifestyle groups respectively. No
      significant differences in the defined endpoints were noted. None of the patients
      had an adverse event that was related to weight loss or exercise.  CONCLUSIONS:
      This study is the first to assess the effects of a comprehensive program of
      dietary, behavioral, and exercise modifications in this population. Institution
      of lifestyle modification in patients with systolic heart failure and metabolic
      syndrome was well tolerated, but did not result in significant weight loss.

PMID- 23125957
TI  - Safety reporting - Making it safely effective or effectively safe?

PMID- 23125956
TI  - Environmental Risk and Protective Factors and Their Influence on the Emergence of
      Psychosis.
AB  - Environmental risk and protective factors in schizophrenia play a significant
      role in the development and course of the disorder. The following article reviews
      the current state of evidence linking a variety of environmental factors and
      their impact on the emergence of psychotic disorders. The environmental factors
      include pre- and perinatal insults, stress and trauma, family environment, and
      cannabis use. The review of evidence is followed by case examples and clinical
      applications to facilitate the integration of the evidence into clinical
      practice.

PMID- 23125958
TI  - Government's role in shaping public perceptions about clinical research.

PMID- 23125959
TI  - Knowledge, attitude and perception/practices (KAP) of medical practitioners in
      India towards adverse drug reaction (ADR) reporting.
AB  - OBJECTIVE: The objective was to assess knowledge, attitude and
      perceptions/practices (KAP) of medical practitioners (MPs) in India towards
      Adverse Drug Reaction (ADR) reporting. MATERIALS AND METHODS: A questionnaire was
      designed for assessment of KAP of medical practitioners in India toward ADR
      reporting. This questionnaire was administered to 2-3 medical practitioners from
      each zone prior to administering final questionnaire which was approved by Disha
      Independent Ethics Committee, Mumbai. 1200 medical practitioners (about 300 from
      each zone) from India were selected randomly. RESULTS: 1000 medical practitioners
      out of 1200 (90%), selected at random were approached. A total of 870 provided
      responses to the questionnaire, giving a response rate of 73% of 1200 selected
      randomly. A total of 47.5% respondents reported that they were aware of
      Government ADR centers. A total of 59.2% reported that they are familiar with the
      procedure of reporting ADRs to Government centers. However, only 18.5% of MPs
      have reported the observed ADRs to Government ADR centers. As against this
      relatively large number of MPs (87.9%) have reported ADRs observed during their
      routine practice to medical representatives of pharmaceutical company and NGOs
      (non-Govt. Organizations). A total of 80.5% of respondents agreed that safety
      plays an important role and 96% reported that ADR centers are useful. However,
      only 55.6% of respondents have reported that there is a need for ADR centers.
      CONCLUSION: The study reveals that practitioners are aware of ADR reporting;
      their perception toward ADR reporting is right but it is not reflected when it
      comes to the act of reporting of ADRs. In our sample of 870 respondents only 18.5
      % reported ADRs to some organizations. Only 5% of respondents recorded the
      details of ADR and reported to the manufacturer and 1% of respondents to
      government health ministry. Thus, medical practitioners in India appear to have a
      good knowledge about ADR reporting, the right perception toward ADR reporting.
      However, as far as practice of ADR reporting is concerned it is discouraging.

PMID- 23125960
TI  - Knowledge and attitudes of HIV-infected patients on antiretroviral therapy
      regarding adverse drug reactions (ADRs) in selected hospitals in Nigeria.
AB  - PURPOSE: The study evaluated the knowledge and attitudes of HIV-infected patients
      on ART regarding ADRs following routine patient counseling and education in
      selected hospitals in Nigeria. MATERIALS AND METHODS: From 36,459 HIV-infected
      patients on ART in the 36 selected hospitals, a study-specific instrument was
      administered to 3,650 patients in a cross-sectional study. Patients were provided
      counseling and education on ADRs before and after commencing ART. Factor analysis
      was performed using principal components extraction. Item score means above
      midpoint (3.7) on a 5-point scale were regarded as positive attitudes and below
      as negative attitudes. A chi-square test was used for inferential statistics;
      P<0.05 was used to determine statistical significance. RESULTS: The mean
      questionnaire return rate was 47.5%. Data from 2329 (63.8%) participants were
      analyzed, 63.1% females and 34.4% aged 25-34 years old. A total of 80.1%
      participants accepted to have been counseled on ADRs; 65.8% knew that all
      medicines cause some kind of adverse effects; 55.1% knew the adverse effects of
      their medicines; 60.8% knew what to do when they suspect ADRs and it included
      mainly reporting to the healthcare provider (88.1%). However, only 31.9% had
      experienced ADRs previously. The knowledge of ADRs was associated with gender and
      educational and employment status of the patients (P<0.05). A total of 95.6%
      reported self-efficacy to ART. Majority of the rated attitude score means were
      >3.7 which denotes positive attitudes to ADRs. Three extracted factors accounted
      for 73.1% of cumulative variability. All attitude items had very significant
      loadings of >=0.5. CONCLUSION: Overall, participants reported good knowledge and
      positive attitudes to adverse effects of their medicines compared to what was
      reported previously. The patient counseling and education on drug therapy
      provided to patients may have contributed to these findings and are highly
      recommended.

PMID- 23125961
TI  - Management of third stage of labor with misoprostol: A comparison of three routes
      of administration.
AB  - BACKGROUND AND CONTEXT: Misoprostol is a versatile drug with an effective
      uterotonic effect on the postpartum uterine tissue and is used through various
      routes during the third stage of labor. AIMS AND OBJECTIVES: A randomized
      prospective study was carried out to analyze the most effective route for
      misoprostol administration, with an emphasis on parturients' acceptability and
      compliance, a possible shortening of the duration of the third stage of labor,
      minimization of blood loss and possibly reducing the incidence of potential side
      effects. MATERIALS AND METHODS: The study groups comprised of 300 healthy
      parturients, divided randomly into three groups of 100 parturients each, who were
      administered misoprostol 400 MUg through the oral (O), rectal (R), and sublingual
      (S) routes, respectively, during the third stage of labor. Estimation of blood
      loss was measured in terms of fall in hemoglobin, hematocrit, and packed cell
      volume (PCV) levels, and duration of the third stage of labor was also compared.
      RESULTS: The mean duration for the third stage of labor was significantly shorter
      in group S (3.62 minutes) as compared to R (4.12 minutes), and O (4.94 minutes)
      (P = 0.02). The average blood loss was observed to be the least in the group S
      (210 ml) as compared to group R (230 ml), and group O. The incidence of shivering
      and fever was observed to be significantly higher (25 and 15%) in the parturients
      of group S (P < 0.05). CONCLUSIONS: All routes were equally effective in managing
      the third stage of labor, but administration of misoprostol through the rectal
      route evoked better acceptability, comparable efficacy, and had an incidence of
      minimal side effects.

PMID- 23125962
TI  - Diabetes mellitus: Exploring the challenges in the drug development process.
AB  - Diabetes mellitus has reached epidemic proportions and continues to be a major
      burden on society globally. The International Diabetes Federation (IDF) estimated
      the global burden of diabetes to be 366 million in 2011 and predicted that by
      2030 this will have risen to 552 million. In spite of newer and effective
      treatment options, newer delivery and diagnostic devices, stricter glycaemic
      targets, better treatment guidelines and increased awareness of the disease,
      baseline glycosylated hemoglobin remains relatively high in subjects diagnosed
      and treated with type 2 diabetes. The search continues for an ideal anti diabetic
      drug that will not only normalize blood glucose but also provide beta cell rest
      and possibly restoration of beta cell function. The development of anti diabetic
      drugs is riddled with fundamental challenges. The concept of beta cell rest and
      restoration is yet to be completely understood and proven on a long term. The
      ideal therapeutic approach to treating type 2 diabetes is not yet determined. Our
      understanding of drug safety in early clinical development is primarily limited
      to "Type A" reactions. Until marketing authorization most drugs are approved
      based on the principle of confirming non-inferiority with an existing gold
      standard or determining superiority to a placebo. The need to obtain robust
      pharmaco-economic data prior to marketing authorization in order to determine
      appropriate pricing of a new drug remains a major challenge. The present review
      outlines some of the challenges in drug development of anti-diabetic drugs citing
      examples of pulmonary insulin, insulin analogues, thiazolidinediones and the GLP1
      analogues.

PMID- 23125963
TI  - What to use to express the variability of data: Standard deviation or standard
      error of mean?
AB  - Statistics plays a vital role in biomedical research. It helps present data
      precisely and draws the meaningful conclusions. While presenting data, one should
      be aware of using adequate statistical measures. In biomedical journals, Standard
      Error of Mean (SEM) and Standard Deviation (SD) are used interchangeably to
      express the variability; though they measure different parameters. SEM quantifies
      uncertainty in estimate of the mean whereas SD indicates dispersion of the data
      from mean. As readers are generally interested in knowing the variability within
      sample, descriptive data should be precisely summarized with SD. Use of SEM
      should be limited to compute CI which measures the precision of population
      estimate. Journals can avoid such errors by requiring authors to adhere to their
      guidelines.

PMID- 23125964
TI  - Protocol deviation and violation.

PMID- 23125965
TI  - From the world of clinical research.

PMID- 23125967
TI  - Synanthropic rodents as possible reservoirs of shigatoxigenic Escherichia coli
      strains.
AB  - Shigatoxigenic Escherichia coli (STEC) strains are worldwide zoonotic pathogen
      responsible for different cases of human disease including hemolytic uremic
      syndrome (HUS). Transmission of STEC to humans occurs through the consumption of
      food and water contaminated by faeces of carriers and by person-to-person
      contact. The objective of this study was two-fold: (1) to investigate whether
      synanthropic rodents are possible reservoirs of STEC in the urban area and (2)
      whether a particular genus out of synanthropic rodent is the principal carrier of
      STEC. One hundred and forty-five rodents were captured in Buenos Aires City.
      Screening for stx1/stx2 and rfbO157 was done by PCR from the confluence zone.
      STEC isolates were further characterized with biochemical tests by standard
      methods. Additional virulence factors (eae, ehxA, and saa) were also determined
      by PCR. Forty-one of the rodents were necropsied and sample of kidney and small
      and large intestine were taken for histopathological diagnosis. The samples
      sections were stained with hematoxylin-eosin, and observed by light microscopy to
      evaluate the systemic involvement of these species in natural infections. STEC
      was isolated from seven out of 27 suspect animals at screening. The following
      genotypes were found in the STEC strains: stx1/stx2/ehxA (1), stx2 (4), stx2/ehxA
      (1), stx2/ehxA/eae (1). Neither gross nor microscopic lesions compatible with
      those produced by Shiga toxin were observed in the studied organs of necropsied
      rodents. The bivariate analysis including the 145 rodent's data showed that the
      isolation of STEC is associated positively to Rattus genus. This synanthropic
      species may play a role in the transmissibility of the agent thus being a risk to
      the susceptible population. Their control should be included specifically in
      actions to dismiss the contamination of food and water by STEC in the urban area,
      as additional strategies for epidemiological control.

PMID- 23125968
TI  - Novel Mechanism for Sleep-Wake Control: Electrical Coupling.

PMID- 23125966
TI  - Telomere components as potential therapeutic targets for treating microbial
      pathogen infections.
AB  - In a number of microbial pathogens that undergoes antigenic variation to evade
      the host's immune attack, genes encoding surface antigens are located at
      subtelomeric loci, and recent studies have revealed that telomere components play
      important roles in regulation of surface antigen expression in several of these
      pathogens, indicating that telomeres play critical roles in microbial pathogen
      virulence regulation. Importantly, although telomere protein components and their
      functions are largely conserved from protozoa to mammals, telomere protein
      homologs in microbial pathogens and humans have low sequence homology. Therefore,
      pathogen telomere components are potential drug targets for therapeutic
      approaches because first, most telomere proteins are essential for pathogens'
      survival, and second, disruption of pathogens' antigenic variation mechanism
      would facilitate host's immune system to clear the infection.

PMID- 23125969
TI  - Positively charged polymer brush-functionalized filter paper for DNA sequence
      determination following Dot blot hybridization employing a pyrrolidinyl peptide
      nucleic acid probe.
AB  - As inspired by the Dot blot analysis, a well known technique in molecular biology
      and genetics for detecting biomolecules, a new paper-based platform for
      colorimetric detection of specific DNA sequences employing peptide nucleic acid
      (PNA) as a probe has been developed. In this particular study, a pyrrolidinyl PNA
      bearing a conformationally rigid d-prolyl-2-aminocyclopentanecarboxylic acid
      backbone (acpcPNA) was used as a probe. The filter paper was modified to be
      positively charged with grafted polymer brushes of quaternized
      poly(dimethylamino)ethyl methacrylate (QPDMAEMA) prepared by surface-initiated
      polymerization of 2-(dimethylamino)ethyl methacrylate from the filter paper via
      ARGET ATRP followed by quaternization with methyl iodide. Following the Dot blot
      format, a DNA target was first immobilized via electrostatic interactions between
      the positive charges of the QPDMAEMA brushes and negative charges of the
      phosphate backbone of DNA. Upon hybridization with the biotinylated pyrrolidinyl
      peptide nucleic acid (b-PNA) probe, the immobilized DNA can be detected by naked
      eye observation of the yellow product generated by the enzymatic reaction
      employing HRP-labeled streptavidin. It has been demonstrated that this newly
      developed assay was capable of discriminating between complementary and single
      base mismatch targets at a detection limit of at least 10 fmol. In addition, the
      QPDMAEMA-grafted filter paper exhibited a superior performance to the commercial
      membranes, namely Nylon 66 and nitrocellulose.

PMID- 23125970
TI  - Solvent-assisted mechanochemistry.
AB  - The literature on solvent-assisted mechanochemistry is reviewed with a view to
      linking observations concerning the applicability of the technique to theories of
      its mechanism, and summarizing the advantages and limitations of the technique
      when applied to a variety of different reaction types. Previously unnoticed links
      between "solvent-free" and solvent-assisted reaction mechanisms are presented,
      and reasons why the method should be considered more widely by synthetic chemists
      are given.

PMID- 23125971
TI  - One-pot synthesis of colloidal silicon quantum dots and surface functionalization
      via thiol-ene click chemistry.
AB  - A solution method for preparing surface functionalized colloidal silicon quantum
      dots (SiQDs) is presented. SiQDs prepared by this method are reasonably
      monodispersed and can be further functionalized via thiol-ene click reactions to
      introduce specific functionalities (i.e. -NH(2), -COOH, -SO(3)(-), alkane,
      alkene).

PMID- 23125972
TI  - Mutual binding of polymer end-groups by complementary pi-pi-stacking: a molecular
      "Roman Handshake".
AB  - Self-complementary tweezer-molecules based on a naphthalenediimide core self
      assemble into supramolecular dimers through mutual pi-pi-stacking and hydrogen
      bonding. The resulting motif is extremely stable in solution (K(a) = 10(5) M(
      1)), and its attachment to one terminal position of a poly(ethylene glycol) chain
      leads to a doubling of the polymer's apparent molecular weight.

PMID- 23125973
TI  - Facile growth of a single-crystal pattern: a case study of HKUST-1.
AB  - In order to fabricate metal-organic framework (MOF) based devices, it is
      desirable to precisely position high-quality and mono-sized MOF crystals on
      supports. In this work, we demonstrate a facile solution procedure for the
      fabrication of oriented and monodispersed single-crystal MOF pattern. We expect
      that such capability will expand the scope of applications of MOFs to advanced
      fields.

PMID- 23125974
TI  - Enhancement of the visible light absorption intensity of microporous
      vanadosilicate AM-6.
AB  - AM-6 with high intensity visible light absorption at 400-800 nm was synthesized
      via a hydrothermal route in the presence of F(-) ions. Structure characterization
      and DFT calculations indicate that the unusual optical properties originate from
      the connection of octahedral VO(6) wires with distorted tetrahedral VO(4) units,
      which are stabilized in the framework of AM-6.

PMID- 23125975
TI  - Ultrafast charge separation in supramolecular tetrapyrrole-graphene hybrids.
AB  - Supramolecular donor-acceptor hybrids composed of few-layer graphene as an
      electron acceptor and phthalocyanine or porphyrin bearing four pyrene entities as
      photosensitizer donors have been synthesized, and occurrence of ultrafast charge
      separation in the order of 10(11)-10(12) s(-1) due to close proximity of the
      donor and acceptor entities is demonstrated.

PMID- 23125976
TI  - A bifunctionalized organic-inorganic hybrid silica: synergistic effect enhances
      enantioselectivity.
AB  - An imidazolium-based bifunctional heterogeneous catalyst exhibits excellent
      catalytic efficiency in asymmetric transfer hydrogenation of aromatic ketones in
      aqueous medium. The superior catalytic performance and the enhanced
      enantioselectivity is attributed to the synergistic effect of salient imidazolium
      phase-transfer function and the confined nature of the chiral organoiridium
      catalyst.

PMID- 23125977
TI  - Deep cavitands featuring functional acetal-based walls.
AB  - The synthesis of deep cavitands with functionalized acetals as a fourth-wall is
      described. Recognition properties and stabilities of the complexes of two
      representative cavitands with aliphatic, aromatic, carbocyclic and adamantane
      guests were evaluated by NMR methods.

PMID- 23125978
TI  - Proton-electron transfer pathways in the reactions of peroxyl and dpph radicals
      with hydrogen-bonded phenols.
AB  - The kinetics of the reaction of peroxyl and dpph radicals with phenols H-bonded
      to N-bases have been studied for the first time. Electron-transfer processes are
      observed in MeCN but only with the dpph radical.

PMID- 23125979
TI  - A one-step homogeneous plasmonic circular dichroism detection of aqueous mercury
      ions using nucleic acid functionalized gold nanorods.
AB  - In this work, we report the application of gold nanorods ladder assemblies as
      chiroptical sensors for detecting mercury ions (Hg(2+)). By taking advantage of
      the Hg(2+)-mediated T-T base pair of DNA and the high sensitivity of CD
      measurements, the method offers a simple and sensitive detection of target Hg(2+)
      residues in water. Therefore, the developed method will be a promising tool for
      monitoring heavy metal ions, other small molecules and biomacromolecules.

PMID- 23125980
TI  - Porous organic cage crystals: characterising the porous crystal surface.
AB  - The characterisation of porous crystalline solids often relies on single crystal
      X-ray diffraction, which does not give direct information about the surface of
      the material. Here, crystals of a porous organic cage, CC3-R, are investigated by
      atomic force microscopy and shown to possess two distinct gas-solid interfaces,
      proving that the bulk crystal structure is preserved at the porous crystal
      surface.

PMID- 23125981
TI  - In vitro selection of a photo-responsive peptide aptamer using ribosome display.
AB  - A photo-responsive peptide aptamer against microbeads immobilized streptavidin
      was isolated using in vitro selection combined with photo-manipulation. This is
      the first example of the introduction of a peptide aptamer in the photo-control
      of dynamic molecular recognition.

PMID- 23125982
TI  - Catalytic coupling of nitriles with amines to selectively form imines under mild
      hydrogen pressure.
AB  - Imines are selectively formed by coupling of nitriles and amines under mild
      hydrogen pressure. The reaction is catalyzed by a bipyridine-based PNN Ru(II)
      pincer complex and proceeds under mild, neutral conditions at 4 bar of H(2).

PMID- 23125983
TI  - One-step synthesis of novel glycosyltransferase inhibitors.
AB  - A one-step synthesis of two 5-CF(3) UDP-sugars is reported. These non-natural
      sugar-nucleotides are micromolar inhibitors of two different
      galactosyltransferases.

PMID- 23125984
TI  - Bio-inspired catechol chemistry: a new way to develop a re-moldable and
      injectable coacervate hydrogel.
AB  - A new way is demonstrated to develop a bio-inspired coacervate hydrogel by
      following catechol chemistry showing injectable and re-moldable physical
      properties. The formed coacervate shows potential long-term stability under
      water. Depending on pH, formation of the coacervate has been verified which is
      confirmed by XPS and zeta potential measurements.

PMID- 23125985
TI  - Bioluminescence resonance energy transfer coupled near-infrared quantum dots
      using GST-tagged luciferase for in vivo imaging.
AB  - Bioluminescence resonance energy transfer coupled near-infrared quantum dots
      using glutathione-s-transferase (GST) tagged luciferase were synthesized as
      luminescent probes for in vivo imaging.

PMID- 23125986
TI  - Neutrophil gelatinase-associated lipocalin (NGAL): the laboratory perspective.

PMID- 23125999
TI  - Temperature and salt effects on settling velocity in granular sludge technology.
AB  - Settling velocity is a crucial parameter in granular sludge technology. In this
      study the effects of temperature and salt concentrations on settling velocities
      of granular sludge particles were evaluated. A two-fold slower settling velocity
      for the same granules was observed when the temperature of water decreases from
      40  degrees C to 5  degrees C. Settling velocities also decreased with increasing
      salt concentrations. Experiments showed that when granules were not pre-incubated
      in a solution with increased salt concentration, they initially floated. The time
      dependent increase in mass and hence in settling speed of a granule due to salt
      diffusion into the granule was dependent on the granule diameter. The time needed
      for full salt equilibrium with the bulk liquid took 1 min for small particles
      from the top of the sludge bed and up to 30 min for big granules from the bottom
      of the sludge bed. These results suggest that temperature and salt concentration
      are important parameters to consider in the design, start-up and operation of
      granular sludge reactors and monitoring of these parameters will aid in a better
      control of the sludge management in anaerobic and aerobic granular sludge
      technology. The observations also give an explanation for previous reports which
      were suggesting that a start-up of granular sludge reactors is more difficult at
      low temperatures.

PMID- 23125998
TI  - Canadian HIV Pregnancy Planning Guidelines: No. 278, June 2012.
AB  - OBJECTIVE: Four main clinical issues need to be considered for HIV-positive
      individuals and couples with respect to pregnancy planning and counselling: (1)
      pre-conceptional health; (2) transmission from mother to infant, which has been
      significantly reduced by combined antiretroviral therapy; (3) transmission
      between partners during conception, which requires different prevention and
      treatment strategies depending on the status and needs of those involved; and (4)
      management of infertility issues. The objective of the Canadian HIV Pregnancy
      Planning Guidelines is to provide clinical information and recommendations for
      health care providers to assist HIV-positive individuals and couples with their
      fertility and pregnancy planning decisions. These guidelines are evidence- and
      community-based and flexible, and they take into account diverse and intersecting
      local/population needs and the social determinants of health. OUTCOMES: Intended
      outcomes are (1) reduction of risk of vertical transmission and horizontal
      transmission of HIV, (2) improvement of maternal and infant health outcomes in
      the presence of HIV, (3) reduction of the stigma associated with pregnancy and
      HIV, and (4) increased access to pregnancy planning and fertility services.
      EVIDENCE: PubMed and Medline were searched for articles published in English or
      French to December 20, 2010, using the following terms: "HIV" and "pregnancy" or
      "pregnancy planning" or "fertility" or "reproduction" or "infertility" or
      "parenthood" or "insemination" or "artificial insemination" or "sperm washing" or
      "IVF" or "ICSI" or "IUI." Other search terms included "HIV" and 'horizontal
      transmission" or "sexual transmission" or "serodiscordant." The following
      conference databases were also searched: Conference on Retroviruses and
      Opportunistic Infections, International AIDS Conference, International AIDS
      Society, Interscience Conference on Antimicrobial Agents and Chemotherapy, the
      Canadian Association of HIV/AIDS Research, and the Ontario HIV Treatment Network
      Research Conference. Finally, a hand search of key journals and conferences was
      performed, and references of retrieved articles were reviewed for additional
      citations. Subsequently, abstracts were categorized according to their primary
      topic (based on an outline of the guidelines) into table format with the
      following headings: author, title, study purpose, participants, results and
      general comments. Finally, experts in the field were consulted for their opinions
      as to whether any articles were missed. VALUES: The quality of evidence was rated
      using the criteria described in the Report of the Canadian Task Force on
      Preventive Health Care. Recommendations for practice were ranked according to the
      method described in that report (Table) and through use of the Appraisal of
      Guidelines Research and Evaluation instrument for the development of clinical
      guidelines. SPONSORS: The Society of Obstetricians and Gynecologists of Canada,
      Women and HIV Research Program, Women's College Research Institute, Women's
      College Hospital, University of Toronto, Abbott Laboratories Canada, the Ontario
      HIV Treatment Network, the Canadian Institutes of Health Research, and the
      Canadian HIV Trials Network.

PMID- 23126000
TI  - Exercise testing in the clinical management of patients affected by pulmonary
      arterial hypertension.
AB  - Patients affected by pulmonary arterial hypertension (PAH) show a reduced
      exercise tolerance with early occurrence of dyspnoea and fatigue. The origin of
      functional capacity limitation is multifactorial and several mechanisms have been
      proposed, including right heart failure, which leads to a limited increase in
      cardiac output during exercise, and hyperventilation with a reduced perfusion of
      properly ventilated alveoli. In addition, abnormalities in arterial blood gases
      are observed, with the occurrence of hypoxemia and hypocapnia, related to an
      abnormal ventilation/perfusion match, gas diffusion abnormalities, low mixed
      venous oxygen saturation and to the development of intra- and extra-pulmonary
      right-to-left shunts. At present, the 6-minute walking test is the most used
      method to assess exercise tolerance in PAH; it is also useful to monitor the
      response to therapy and provides prognostic information. However, the assessment
      of functional capacity by cardiopulmonary exercise test (CPET) seems to be more
      complete, because CPET allows for discrimination between the metabolic,
      cardiovascular and pulmonary components of exercise limitation. Moreover, CPET
      estimates the severity of disease and assesses patients' prognosis and response
      to therapy. In PAH, a typical CPET-response is observed, characterized by a
      severe reduction in peak VO2, work rate, O2 pulse and anaerobic threshold and by
      a marked increase in VE/VCO2 slope and in the dead space to tidal volume ratio.
      However, the use of CPET should be limited to experienced centres. This review
      will focus on resting lung function and exercise tolerance tests, showing that
      CPET can provide the physiological explanation of functional limitation in PAH.

PMID- 23126001
TI  - Recommendations for physical activity, recreation sport, and exercise training in
      paediatric patients with congenital heart disease: a report from the Exercise,
      Basic & Translational Research Section of the European Association of
      Cardiovascular Prevention and Rehabilitation, the European Congenital Heart and
      Lung Exercise Group, and the Association for European Paediatric Cardiology.
AB  - All children have a natural need to move, play, and perform activities. Physical
      activity is necessary for optimal physical, emotional, and psychosocial
      development for healthy children as well as children with congenital heart
      disease (CHD). In this paper we provide recommendations for physical activity,
      recreational sport, and exercise training in children and adolescents with CHD.
      In general, children with CHD should be advised to comply with public health
      recommendations of daily participation in 60 min or more of moderate-to-vigorous
      physical activity that is developmentally appropriate and enjoyable and involves
      a variety of activities. While all patients with CHD can participate and benefit
      from physical activity and exercise, those with specific lesions or complications
      may require counselling regarding precautions and recommendations.

PMID- 23126002
TI  - Addressing the growing burden of atrial fibrillation: evidence, sustainability
      and accessibility more important than territory.

PMID- 23126003
TI  - Lifestyle risk reduction interventions in atrial fibrillation: a systematic
      review.
AB  - BACKGROUND: The burden of atrial fibrillation (AF) is escalating even though it
      is potentially modifiable. Affected persons, at high risk of stroke and death,
      are typically not targeted for risk reduction. We aimed to determine if risk
      factor interventions can improve physical functioning, health-related quality of
      life (HRQoL) and cardiovascular risk in AF. METHODS: We conducted a systematic
      review of clinical trials evaluating lifestyle and biomedical risk reduction
      interventions in AF patients. Trials were identified by searching electronic
      databases, reference lists and grey literature. Trials were included if conducted
      by a health professional, and reported changes in multiple risk factor levels or
      HRQoL. RESULTS: Five trials, solely exercise based, were identified (166
      participants): two randomised controlled trials, one quasi-experimental and two
      pre-post designs. Exercise capacity improved after 2-12 months in the
      intervention group in all trials. This was assessed by maximal oxygen uptake (two
      trials, 2.5-5.4 ml/kg/min (17-32%) improvement, p < 0.02); six-minute walking
      distance (one trial, 114 m (27%) improvement, p < 0.001); cumulated work (one
      trial, 564 W/min (37%) improvement, p < 0.001) and incremental exercise testing
      (one trial, 11 m/min (10%) improvement, p = 0.05). Three trials evaluated heart
      rate (HR), demonstrating HR reduction at rest (7-13 bpm, p < 0.05) and during
      exercise (9 bpm, p < 0.05). Two trials measured HRQoL, both reporting significant
      improvements in SF-36 physical summary scores. CONCLUSIONS: Literature suggests
      risk reduction interventions for AF can improve exercise levels, HRQoL and reduce
      HR, but the evidence base is small, methodologically compromised and focused on
      physical functioning. High-quality research in this area is required in order to
      help the multitudes of people living with AF.

PMID- 23126004
TI  - Smoking and metabolism; asenapine; irreversible MAOIs.

PMID- 23126005
TI  - [Toward a transatlantic collaboration for the development of a research
      perspective focused on immunomodulation in ARDS].

PMID- 23126006
TI  - [Effects of hydrocortisone in trauma patients].

PMID- 23126007
TI  - [Impact of iron deficiency on fatigue in anaesthesia and intensive care: from
      bench to bedside].

PMID- 23126008
TI  - [Remifentanil: a neuroprotective effect on the developing brain?].

PMID- 23126010
TI  - Retraction statement: Behavioural effects of automatic interpersonal versus
      intergroup social comparison.

PMID- 23126009
TI  - Retraction statement: It depends on how you look at it: being versus becoming
      mindsets determine responses to social comparisons.

PMID- 23126011
TI  - Characterising hepatic mitochondrial function as a model for systemic toxicity: a
      commentary.

PMID- 23126012
TI  - 1 October news.

PMID- 23126013
TI  - Cardioprotection with adenosine in patients with ST-segment elevation myocardial
      infarction.

PMID- 23126014
TI  - Dl-3-n-butylphthalide and its emerging beneficial effects in neurology.

PMID- 23126015
TI  - [Activity of phenylalanine-ammonia-lyase in callus cultures of sugar beat
      infected by Acholeplasma].
AB  - The effect of Acholeplasma laidlawii var. granulum 118 on activity of
      phenylalanine-ammonia-lyase (PAL) in callus cultures of sugar beat was
      researched. The optimal conditions of enzyme reaction were: using the L
      phenilalanine as a substrate, pH 8.4-8.8, the temperature optimum 38-40 degrees
      C. It was established that at the infecting of sugar beat callus culture by
      phytopathogenic mollicute the PAL activity was temporarily increased and reached
      its maximum after 2 h of infecting. Then it gradually decreased and in 24 h
      reached its initial level. An increase of PAL activity of plant is considered as
      protective reaction in response to the action of pathogen.

PMID- 23126016
TI  - [The action of hydrogen peroxide on mutants of Streptomyces globisporus 1912 with
      different carotene-synthesizing activity].
AB  - The paper deals with dependence of survival of Crt(+)- and Crt- mutants of
      Streptomyces globisporus 1912 in conditions of oxidizing stress caused by
      hydrogen peroxide on the level of lycopene and beta-carotene biosynthesis. Pink
      mutants 4Lcp, RVLcp and R3Lcp, which produce lycopene, are the most resistant to
      hydrogen peroxide. Red mutants 4Crt, 6Crt, 7Crt, 7Y RVCrt, R3Crt--producers of
      lycopene and beta-carotene have the average level of resistance to H2O2.
      Pigmentless mutants (Crt-) 4W, 4W1, 7W2 and yellow one 7Y have preserved
      sensitivity to H2O2 characteristic of the initial strain 1912.

PMID- 23126017
TI  - [Dynamics of diazotrophic bacteria number in the root zone of wheat Vrn lines
      isogenic by genes].
AB  - The number of diazotrophic bacteria and nitrogenase activity in the root zone of
      isogenic monogene-dominant Vrn lines were measured in the field experiments
      throughout their vegetation from tillering to heading. The total number of
      diazotrophic bacteria and nitrogenase activity in the root zone of these lines
      during this period were increased irrespective of their genotypes. The above
      indices of the winter cultivar (Vrn loci bottom recessive) were lower than those
      of the spring lines--Vrn-A1, Vrn-B1 and Vrn-D1. Plants of Vrn-B1 line have the
      lowest indices among the spring lines with the exception of some indices. This
      line plants flowered later than those of Vrn-A1 and Vrn-D1 lines. We hypothesized
      the differences between plants of these lines as to nitrogen fixation activity
      and the number of diazotrophic bacteria are mediately determined by Vrn loci
      through their effects on metabolism intensity and assimilate reflux in the form
      of root exudates, therefore the total number of diazotrophic bacteria and
      nitrogenase activity increases.

PMID- 23126018
TI  - [Future of management of H. pylori infection. Discussion].

PMID- 23126019
TI  - [Q & A. Case of metastatic cancer discovered at the detection of melena].

PMID- 23126020
TI  - Canadian Guidelines on Parkinson's Disease.

PMID- 23126021
TI  - [Annotation to the history of Merkur University Hospital and to the development
      of clinical cytology in Merkur University Hospital].

PMID- 23126022
TI  - [Perception of cytology from the clinician standpoint].

PMID- 23126023
TI  - [55 years of clinical cytology in Zagreb--55 reasons for anniversary].

PMID- 23126024
TI  - [50 years of the Laboratory for Gynecologic Cytology and Clinical Genetics].

PMID- 23126025
TI  - [Why is cytology a profession (branch), not a method? Ten rules for success of
      the cytology profession].
AB  - Clinical cytology is an interdisciplinary medical diagnostic profession that
      integrates clinical, laboratory and analytical fields along with final
      cytologist's expert opinion. Cytology involves nonaggressive, minimally invasive
      and simple for use procedures that are fully acceptable for the patient. Cytology
      offers rapid orientation, while in combination with additional technologies on
      cytologic smear analysis (cytochemistry, immunocytochemistry for cell marker
      analysis, computer image analysis) or sophisticated methods on cytologic samples
      (flow cytometry, molecular and cytogenetic analysis) it plays a major role in the
      diagnosis, subtyping and prognosis of malignant tumors. Ten rules for successful
      performance in cytology are as follows: 1) due knowledge of overall cytology
      (general cytologist); 2) inclusion in all stages of cytologic sample manipulation
      from sampling through reporting; 3) due knowledge of additional technologies to
      provide appropriate interpretation and/or rational advice in dubious cases; 4) to
      preserve dignity of the profession because every profession has its advantages,
      shortcomings and limitations; 5) to insist on quality control of the performance,
      individual cytologists and cytology team; 6) knowledge transfer to young
      professionals; 7) assisting fellow professionals in dubious cases irrespective of
      the time needed and fee because it implies helping the patient and the profession
      itself; 8) experience exchange with other related professionals to upgrade mutual
      understanding; 9) to prefer the interest of the profession over one's own
      interest; and 10) to love cytology.

PMID- 23126026
TI  - [The purpose of clinical laboratory accreditation in transplantation medicine].
AB  - Although transplantation of solid organs has become a more standardized method of
      treatment, liver transplantation represents an exceptional multidisciplinary
      clinical procedure requiring understanding of specific pathophysiological changes
      that occur in the end stage of liver disease. Liver transplantation has been
      performed at Merkur University Hospital since 1998, with 360 transplantations
      performed to date. The most common indications are alcohol liver disease,
      cirrhosis caused by hepatitis B and C virus, hepatocellular carcinoma and
      cryptogenetic liver cirrhosis. Laboratory tests required for liver
      transplantation are performed at Department of Clinical Chemistry, Merkur
      University Hospital, accredited according to ISO 15189 in 2007 for the areas of
      clinical chemistry, laboratory hematology and coagulation, laboratory immunology
      cell immunophenotyping, and molecular diagnosis. The complexity of liver
      transplant patients requires constant interaction between the anesthesiologist
      team and clinical laboratory, which has to ensure fast and efficient
      intraoperative monitoring of biochemical and liver profile: electrolytes and acid
      base status, complete blood count, coagulation profile and monitoring of graft
      function according to the individual patient's health status. Dynamics of
      intraoperative changes is measured in whole arterial blood samples on a Nova
      Biomedical Stat Profile Critical Care Xpress mobile acid-base analyzer. Frequent
      monitoring of ionized calcium and magnesium levels is very important because of
      citrated blood transfusion and for appropriate therapeutic procedure. During
      anhepatic stage, there is a progressive increase in lactate level concentration.
      After reperfusion, a rapid increase in lactate clearance is an excellent
      indicator of stable graft initial function and its adequate size. During the
      transplantation procedure, there is usually a biphasic acid-base disturbance
      characterized by metabolic acidosis and then by metabolic alkalosis. The loss of
      base equivalents starts during the dissection stage and accelerates during the
      anhepatic stage. Fast and efficient intraoperative monitoring of hematological
      tests and coagulation status is of great help in detecting the cause of possible
      hemorrhage and consequential complications during transplantation procedure. The
      possibility of organ and tissue transplantation mostly depends on well regulated
      international cooperation in the areas of donating, transplanting and exchange of
      required organs and tissues, while laboratory test results must be comparable
      regardless of their geographical area, methodology employed or analytical
      equipment used, which is mainly warranted through accreditation according to the
      international ISO 15189 standard.

PMID- 23126027
TI  - [The unclassifiable myeloproliferative neoplasm--morphological, cytogenetic and
      clinical features].
AB  - Myeloproliferative neoplasm, unclassifiable (MPN,U) has clinical, laboratory and
      morphological features of an MPN but fails to meet the criteria for any of the
      specific MPN entities. Because overlapping features, morphological findings in
      bone marrow, BCR-ABL1 fusion gene, V617F JAK2 mutation and cytogenetic
      abnormalities were analyzed in ten patients diagnosed with MPN,U. Bone marrow
      biopsy showed hypercellularity with trilineage myeloproliferation, dispersed
      megakaryocytes with mild pleomorphism and mature nuclei, and absence of reticulin
      fibrosis. All patients were BCL-ABL1 negative, while V617F JAK2 mutation was
      found in 6 of 8 patients. Trisomy 8 was found in two patients and
      t(6;12)(q12;p13) in one patient. Morphological features of MPN,U are nonspecific,
      however, in study cases they were most similar to diagnostic morphological
      features of polycythemiea vera. The high frequency of V617F JAK2 mutation in
      MPN,U cases analyzed revealed that its presence does not confirm a specific type
      of MPN.

PMID- 23126028
TI  - [Post-transplant lymphoproliferative disease in liver transplant recipients-
      Merkur University Hospital single center experience].
AB  - Post-transplant lymphoproliferative disorder (PTLD) is an increasingly recognized
      condition as the number of solid organ and bone marrow transplant recipients
      increases. It can be a life threatening fulminant disorder and affects
      approximately 8% of solid organ transplant recipients. Epstein-Barr virus (EBV)
      is closely involved in the pathogenesis of PTLD and the majority of PTLD cases
      arise in response to primary infection with EBV or to re-activation of previously
      acquired EBV. The principal risk factors underlying the development of PTLD are
      the degree of overall immunosuppression and EBV serostatus of the recipient. The
      most commonly used pathologic classification of PTLD is the World Health
      Organization classification, which divides PTLD into three categories: early
      lesions, polymorphic PTLD, and monomorphic PTLD. Early lesions are characterized
      by reactive plasmacytic hyperplasia. Polymorphic PTLD may be either polyclonal or
      monoclonal and is characterized by destruction of the underlying lymphoid
      architecture, necrosis, and nuclear atypia. In monomorphic PTLD, the majority of
      cases (>80%) arise from B cells, similar to non-Hodgkin's lymphoma in
      immunocompetent hosts. The most common subtype is diffuse large B-cell lymphoma,
      but Burkitt's/Burkitt's-like lymphoma and plasma cell myeloma are also seen.
      Rarely T-cell variants occur, which include peripheral T-cell lymphomas and,
      rarely, other uncommon types, including gamma/delta T-cell lymphoma and T-natural
      killer (NK) cell varieties. Hodgkin's disease-like lymphoma is very unusual. An
      accurate diagnosis of PTLD requires a high index of suspicion, since the disorder
      may present subtly and/or extranodally. Radiologic evidence of a mass or the
      presence of elevated serum markers (such as increased LDH levels) are suggestive
      of PTLD, with positive finding on ultrasonography, computed tomography, magnetic
      resonance and/or positron emission tomography scanning (possibly indicating
      metabolically active areas) also favoring the diagnosis. The management of PTLD
      poses a major therapeutic challenge and although there is reasonable agreement
      about the overall principles of treatment, there is still considerable
      controversy about the optimal treatment of individual patients. EBV-related PTLDs
      are a significant cause of mortality in patients undergoing orthotopic liver
      transplantation with the observed mortality rate of up to 50%. This paper
      presents the experience acquired at Merkur University Hospital in the diagnosis
      and treatment of patients with liver transplantation and PTLD.

PMID- 23126029
TI  - [Diagnostic and prognostic significance of CD45 cell surface antigen expression
      in hematologic malignancies with main focus on acute leukemias].
AB  - CD45 cell surface antigen is a transmembrane protein with tyrosine phosphatase
      activity, expressed by all nucleated cells of hematopoietic origin, except
      erythrocytes and platelets. Monoclonal antibodies directed against CD45 represent
      irreplaceable tool in differential diagnosis of hematologic and other, non
      hematologic low differentiated malignancies, primarily in cases of: extranodal
      lymphomas, non-hematologic malignancies with nodal or bone marrow localization or
      their metastases in mentioned sites. As cell surface immunophenotype marker, CD45
      is of great value in differentiation of lymphoproliferative diseases subtypes. By
      flow cytometry, based on CD45 expression, the malignant cell population is being
      identified and that fact is used in, not only diagnosis, but also in detection of
      minimal residual disease, especially in cases of CD45 negative acute leukemias.
      Incidence of childhood CD45 negative acute lymphoblastic leukemias (ALL) is about
      10%. Children diagnosed with low CD45 expression ALL generally have better
      prognosis than those with high CD45 expression, especially when cut-off value for
      CD45 expression is set on 90%. We have analyzed CD45 expression by flow cytometry
      in 28 consecutive patients diagnosed with ALL in our institution during a 5-year
      period. Among these patients 7.1% were CD45 negative. A positive correlation
      between CD45 and CD20 expression was found, and a negative correlation between
      CD45 and CD34. In our group of patients, CD45 expression did not have any
      influence on survival.

PMID- 23126030
TI  - [P16NIK4a expression in premalignant cervical lesions].
AB  - Increased expression of viral E6 and E7 oncoproteins within the host cells
      results in an increase in cellular protein p16INK4a expression. That increase may
      serve as a marker for dysplastic and neoplastic cells of the uterine cervical
      epithelium. The aim of this study is to assess the p16INK4a protein expression in
      different stages of cytological abnormality in correlation with the proven high
      oncogenic risk human papillomavirus infection in order to demonstrate its value
      as the diagnostic marker. The study included cervical smear samples of 371
      patient in whom the viral typization was done. In 171 patient, during their
      regular gynaecological examination, along with conventional Pap smear sampling an
      additional smear was taken. Two hundred cervix brush (Rovers Medical DevicesOss,
      the Netherlands) samples were obtained and analyzed by the LBC method and the
      ThinPrep2000 machine. All samples were analyzed cytologically, classified
      according to the Bethesda system, and immunostained with the p16INK4a-specific
      monoclonal antibody E6H4 (MTM Laboratories, Heidelberg, Germany). A significant
      difference is seen in p16 positivity between the cytological diagnosis of a high
      grade cervical squamous intraepithelial lesion and the group with mild dysplasia
      (chi2=146,48; D.F.=4; p<0,01) while most of the mild dysplastic lesions were p16
      negative. In cases of p16 positive mild dysplastic lesions, that positivity is
      the result of viral integration into the host genome, which would imply lesions
      at high risk of further progression. The potential and value of p16INK4a protein
      not only as a prognostic, but also as a diagnostic factor is proved in this way.
      Reproducibility of the p16 staining technique renders it suitable for follow-up
      monitoring as well as for comparison of the cytological results.

PMID- 23126031
TI  - [Standardization in laboratory hematology by participating in external quality
      assurance programs].
AB  - Since 1985, Department of Clinical Chemistry and Laboratory Medicine, Merkur
      University Hospital, Zagreb, has been participating in the International External
      Quality Assessment Scheme for Hematology (IEQAS-H) organized by the World Health
      Organization (WHO). Owing to very good results, in 1987 the Department received a
      certificate of participation in this control scheme. Department has been
      cooperating in the external quality assessment program in laboratory hematology
      which has been continuously performed in Croatia since 1986 by the Committee for
      External Quality Assessment Schemes under the auspices of the Croatian Society of
      Medical Biochemists and School of Pharmacy and Biochemistry, University of
      Zagreb. Nowadays, 186 medical biochemical laboratories are included in the
      National External Quality Assessment program, which is performed three times per
      year. Our Department has participated in the international projects of the
      European Committee for External Quality Assurance Programs in Laboratory Medicine
      (EQALM).

PMID- 23126032
TI  - [Association of CD34 cell surface antigen expression with cytomorphological
      characteristics of acute promyelocytic leukemia blasts and clinical
      characteristics of patients: one center experience].
AB  - The aims of the study were to investigate the association between cytomorphology
      and immunophenotypic expression of CD34 cell surface antigen of blasts and their
      relationship with clinical and laboratory characteristics of patients with acute
      promyelocytic leukemia (APL). Sixteen consecutive patients (male 69% and female
      31%) diagnosed with APL at Department of Hematology, Merkur University Hospital
      between August 1998 and December 2010 were included in the study. The mean age of
      patients was 43.9 (range: 18-78, SD 14.9). The patients' clinical and laboratory
      features, cytomorphological characteristics of APL-blasts and their
      immunophenotype determined by flow cytometry were analyzed. Patients were divided
      into two groups, CD34- and CD34+, and were then compared according to clinical
      and laboratory characteristics. There was no difference according to age, sex or
      white blood cell count between two groups. The mean value of
      hypogranular/agranular APL-blasts was markedly higher in CD34+ group than CD34-
      group (34%, range 9-60, SD 24.4 vs. 11.5%, range 0-38, SD 13.7), with borderline
      statistical significance (P=0.055). CD34- patients had significantly better
      overall survival than CD34+ ones (P=0.02). Patients without Auer rods detected in
      APL-blasts had higher CD34 expression (69.4% +/- 33.8) compared to patients with
      detected Auer rods (7.3% +/- 24.8), but statistical significance was not reached
      (p=0.053). Our results are consistent with the results of other published studies
      and point to the fact that higher CD34 expression and lower cytoplasmic
      granularity of APL-blasts are factors that seem to define a specific subgroup of
      APL patients. Together with other diagnostic tools currently available, they
      could be of value in planning treatment of APL patients.

PMID- 23126033
TI  - [Flow cytometry and acute renal rejection confirmed by histopathologic analysis].
AB  - Transplantation of solid organs, tissues or hematopoietic cells is now standard
      in the treatment of patients with terminal stage disease in order to cure and
      improve the recipients' quality of life. The study included 54 patients having
      undergone single or multiple organ transplantation. All patients received a
      combination of immunosuppressant therapy consisting of corticosteroids,
      calcineurin inhibitor (cyclosporine; tacrolimus), anti-CD25 (daclizumab) and
      mycophenolate-mofetil. In 24 patients, acute rejection was stratified by
      histopathologic analysis of renal biopsy. Fifteen highly sensitized patients were
      administered antithymocyte globulin (ATG) therapy. Absolute count and percentage
      of B/T lymphocyte subsets, NK cells and CD25+ or CD69+ activated T cells were
      measured on a flow cytometer (EPICS XL, Coulter) using single platform
      standardized protocol. Upon ATG therapy, rapid decline to a very low level of T
      and NK cell lymphocyte count was observed, as well of B lymphocytes, resulting in
      redistribution of lymphocyte compartment. Between consecutive measurements,
      kinetic changes of lymphocyte subset numbers (absolute count or percentage) did
      not differ in a large spectrum of immune parameters between the groups with and
      without rejection episode and having received quadruple immunosuppressive
      induction and maintenance therapy. Immunologic monitoring must be initiated prior
      to transplantation and continued consistently and frequently post
      transplantation. Such a program is expensive and time-consuming and stressful for
      the patient, therefore, prospective studies should identify whether treatment
      decisions can be based reliably on these immune parameters. Serial measurement of
      immune cell counts is necessary for maintenance of ATG therapy and could be
      useful for monitoring patient recovery.

PMID- 23126034
TI  - [Fine needle aspirate of lymph node as the analytical sample for
      immunophenotyping].
AB  - In modern clinical laboratory routine, cell analysis by flow cytometry means help
      in setting up the diagnosis by determination of B-lymphocyte clonality and thus
      separation of benign and malignant lymphoproliferative diseases. The aim of this
      study was to assess the value of cytologic diagnosis and adequacy of the material
      obtained by fine needle aspiration (FNA) of lymph nodes for flow cytometry
      analysis in cases of benign lesions and primary malignant lesions of lymph nodes.
      In addition, the aim was to determine B-lymphocyte clonality in different groups
      of benign and malignant lymph node lesions. The study was based on medical
      documentation, cytologic smears of FNA lymph node samples and results of flow
      cytometry immunophenotyping. A total of 239 patients were included over a one
      year period. Patients were classified according to cytologic findings in the
      groups of non-Hodgkin's lymphoma of B cell origin (55%), benign
      lymphoproliferative disease (22%), undefined group of monomorphic population of
      lymphatic cells (16%), and the rest in the group of non-Hodgkin's non B cell
      origin. Study results showed FNA to be an appropriate method for obtaining
      sufficient numbers of cells for analysis by flow cytometry because there was no
      inadequate samples in our study group. In some cases of monomorphic lymphoid cell
      population, cytologic diagnosis was limited to small cell lymphomas, so
      determining the clonality by flow cytometry is crucial in separating malignant
      from benign lymphoproliferative disease. It is concluded that FNA associated with
      the flow cytometry method is a simple and safe method in the diagnosis of
      lymphoproliferative disease.

PMID- 23126035
TI  - [Recollections of the development of clinical cytology at Merkur University
      Hospital].
AB  - My recollections of the development of clinical cytology at Merkur University
      Hospital cover a 30-year period, from 1955 to 1985, and succession of
      generations. The beginning is always exciting, pervaded by youthful enthusiasm,
      while memories are quite nostalgic. That is how I also felt at the "Ruzdic's"
      medical biochemistry laboratory. The founders of clinical cytology at Merkur
      University Hospital were the clinicians Erik Hauptmann (hematologist), Zdenko
      Skrabalo (endocrinologist) and Zvonimir Singer (gynecologist, cytogeneticist),
      with great contribution by Ibrahim Ruzdic (biochemist). As the first head of
      cytology laboratory at University Department of Medicine, I realized what was
      crucial for such a successful development of clinical cytology at our Hospital;
      it was so because new technologies were continuously introduced in agreement with
      clinicians, along with the basic routine cytodiagnosis, while paying special
      attention to staff education (postgraduate study in clinical cytology since 1967;
      residency in cytology since 1974; education of cytotechnologists since 1968). A
      number of MS theses and doctoral dissertations have been defended at our cytology
      laboratories. The Section of Cytology (now Croatian Society of Clinical
      Cytologists, Croatian Medical Association) was founded in 1970, owing to the
      efforts invested by E. Hauptmann. Clinical cytologists from Merkur University
      Hospital contributed to the foundation of the Association of Clinical Cytologists
      of the then Yugoslavia and organized their first congress in 1979; in 1972, we
      were adopted members of the EFCS, while Z. Singer and I. Crepinko are IAC
      members. I wish that written memories help remember the foundation and
      development of clinical cytology at Merkur University Hospital because we should
      not forget that every future has its origin.

PMID- 23126036
TI  - [Education of cytotechnologists--are we satisfied with what we had, what we have,
      and what we want?].
AB  - Our aim is to present training of cytotechnologists in Croatia as it looked in
      the past, as it appears at present, and our desires, needs, and upcoming changes
      necessary in future education of cytotechnologists. Education in cytotechnology
      begins at the School of Health Technicians, where the first organized training of
      cytotechnologists was held in 1968/1969, thanks to the efforts invested by
      Professor Inga Crepinko. After a period of training in a six-month course, during
      the 1981-1992 period training took place in the form of a one-year program
      evaluated as education level V. Since then, efforts to establish education at all
      academic institutions in Croatia have failed. At Medical College, one-year
      training was introduced in 1993, however, for only one generation. Under the
      auspices of the Ministry of Health and Social Welfare and the Croatian Society of
      Clinical Cytology of the Croatian Medical Association, 5 one-year courses with
      630 hours of theoretical classes with practical work and 200 hours of practical
      training in cytologic activities have been held since 2000. Now, we ask ourselves
      was there any reason for us to be satisfied in the past and is it there now. In
      Croatia, there is the need of optimized and standardized training of
      cytotechnologists at the university level, with a valid certificate in European
      countries and a curriculum that will meet the needs of new technologies
      (molecular techniques, LBC, HPV testing, etc.).

PMID- 23126037
TI  - [Significance of participation in programs of external quality assessment in
      molecular diagnostic--our experience].
AB  - Harmonization of molecular diagnostic tests in laboratories in the Republic of
      Croatia has only just started. According to laboratory accreditation standard ISO
      15189 participation in external quality assessment (EQA) schemes or programs is a
      prerequisite and support tool for clinical laboratory accreditation process. As
      there are no national quality assurance schemes yet, an European external quality
      assessment (EQA) scheme or program should be found. Because of variation in the
      molecular diagnostic test performance of clinical laboratories across Europe, EQA
      is recognized as a system whereby a set of reagents and techniques are assessed
      by an external provider making inter-laboratory performance comparability
      possible through already integrated recommendations and practice guidelines of
      molecular diagnostic test performance. Today, wide range of various EQA schemes
      and programs already in action have been available and most of them began within
      the last ten years. This paper is therefore intended to present and summarize the
      four-year EQA activities in the Institute of Clinical Chemistry, Merkur
      University Hospital, in three different international EQA schemes: United Kingdom
      National External Quality Assessment Scheme (UK NEQAS), the European Molecular
      Genetic Quality Network (EMQN) and Multi-National External Quality Assay program
      (EQUAL- qual)) and to point out their educational role in standardization of
      laboratory performance of any test intended for patient testing. from a
      laboratory point of view.

PMID- 23126038
TI  - [Causes and frequency of unsatisfactory cervicovaginal smears].
AB  - Inadequate Pap smear by definition is a specimen in which detection of cervical
      epithelial abnormality is impossible or uncertain. This causes poorer detection
      of intraepithelial lesions of a mild and more severe grade, including the
      possible false-negative diagnosis. Sample adequacy is most crucial in the
      evaluation of the finding, alerting the gynecologist to the limitations of the
      finding, its possible inaccuracy, and need to repeat the examination in order to
      obtain as precise results as possible. The aim of the study was to establish the
      frequency and reasons of unsatisfactory cervicovaginal smear samples in the
      course of one year, during which 1594 of 12,242 conventionally obtained cervical
      samples were sorted out as inadequate. These were reassessed with respect to
      their adequacy. Eight percent of the smears in which the evaluation of cell
      abnormality failed due to sample inadequacy were identified and these smears were
      repeated and analyzed for adequacy and presence of abnormality. The most common
      reasons included insufficient endocervical epithelial cells, excessive smear
      thickness, cells obscured with numerous inflammatory elements and erythrocytes,
      and sample inadequacy due to the presence of foreign material, poor fixation or
      staining. Inadequate equipment, insufficient material for cytologic analysis, and
      poor preparation technique may lead to failure to observe abnormality and errors
      in microscopic analysis. This implies each team member's responsibility for the
      accuracy of the result as well for the assurance of specimen adequacy. Reduction
      in the frequency of the reasons mentioned above is possible if internal control,
      performance quality monitoring and continuing education of each team member are
      conducted on a regular basis. The necessity to repeat sampling adds to the cost
      of health care with no considerable increase in the detection rate of epithelial
      abnormalities, inadequate specimens being the most common cause of false-negative
      cytologic findings.

PMID- 23126039
TI  - [Erythrocyte morphology in urine determined by light microscopy in patients with
      bladder cancer].
AB  - A finding of 80% or more of dysmorphic erythrocytes is assumed to point to kidney
      glomeruli, and of 80% or more of isomorphic erythrocytes to lower urinary tract
      as the origin of bleeding. In urine samples without significant origin of
      bleeding, there were 20%-80% of mixed results with both dysmorphic and isomorphic
      erythrocytes. The aim of the study was to show the origin of erythrocytes in
      malignant urine samples. Samples were fresh native urine sediment contrast
      stained with 0.1% safranin solution and analyzed under light microscope (X40).
      Out of 72 patients with malignant cells detected in urine, the origin of
      erythrocytes was identified in 25 patients (nine female and 16 male) through 90
      samples (approximately 3-4 samples per patient); 26 (28.9%) samples did not have
      enough erythrocytes to define their origin, a mixed origin of erythrocytes was
      identified in 33 (36.7%) samples, dysmorphic erythrocytes were found in 25
      (27.9%) samples, and isomorphic erythrocytes in 6 (6.3%) samples. In conclusion,
      there was no specific connection between malignant cell findings in urine and
      origin of erythrocytes. However, the high presence of mixed erythrocyte origin in
      malignant samples may suggest that the existence of a malignant process and renal
      disease should be taken in consideration.

PMID- 23126040
TI  - [Acute plastic bronchitis--case report].
AB  - Plastic bronchitis is a rare disorder characterized by formation and sometimes
      dramatic expectoration of bronchial casts. It may occur at any age, but most
      published cases refer to pediatric population. We report a case of an 81-year-old
      man hospitalized at intensive care unit, who presented with the appearance of
      plastic bronchitis type I. He had profuse expectoration of several pieces, a few
      cm long and up to 1 cm wide, of wormlike reddish-brownish "tissue".
      Histologically, it was a slimy purulent secretion with abundant fibrin and blood
      and with cytopathic effect of herpes virus. The pathogenesis of plastic
      bronchitis is not clear.

PMID- 23126041
TI  - [Isolated myeloid sarcoma involving the mediastinum].
AB  - Myeloid sarcoma is a rare extramedullary solid tumor consisting of immature
      myeloid cells and most commonly involving the bone, skin, lymph nodes, soft
      tissue, gastrointestinal tract and testis. Mediastinal myeloid sarcoma is very
      rare. There are two major types of myeloid sarcoma: granulocytic sarcoma and
      monoblastic sarcoma, according to immature cell type. Myeloid sarcoma is found in
      2%-8% of patients with acute myeloid leukemia (AML). Myeloid sarcoma may develop
      before or concurrently with AML, or may be the initial manifestation of AML
      relapse in previously treated patients. Blast transformation of some form of
      myeloproliferative neoplasm or myelodysplastic syndrome may also manifest as
      myeloid sarcoma. A major differential diagnostic problem is isolated primary
      myeloid sarcoma without bone marrow and peripheral blood involvement, which may
      precede leukemic stage for months or years, and which is frequently misdiagnosed,
      mostly as malignant lymphoma. A case is presented of a 56-year-old female patient
      complaining of weakness, vertigo, dry cough and breathing difficulties. Clinical
      examination revealed enhanced vascular pattern on the right chest and right arm
      edema. Computed tomography (CT) of the thorax showed an expansive growth
      measuring 11 cm craniocaudally in the anterior mediastinum. Fine needle
      aspiration cytology of tumor mass yielded a scarcely cellular sample with
      individual atypical immature cells, fine chromatin structure and scarce cytoplasm
      with occasional granules and Auer rods. Considering the morphological,
      cytochemical and immunocytochemical characteristics of immature cells, the
      diagnosis of myeloid sarcoma was made and verified by histopathology of tumor
      biopsy sample. Immature cells were not found by analysis of bone marrow puncture
      sample, immunophenotyping of bone marrow cells and bone biopsy analysis. As
      immature cell proliferation was not detected in bone marrow and peripheral blood,
      while spread of the disease beyond the mediastinum was ruled out by imaging
      methods (CT, ultrasonography), it was decided to be a primary non-leukemic form
      of mediastinal myeloid sarcoma. Myeloid sarcoma should be taken in consideration
      on differential diagnosis of solid tumors because making an accurate diagnosis is
      necessary for timely initiation of appropriate therapy. Weakly expressed or
      lacking clear signs of myeloid differentiation may hamper morphological
      diagnosis. As isolated myeloid sarcoma is a very rare entity frequently
      resembling lymphoma in clinical presentation, it poses a major diagnostic
      challenge for both morphologists and clinicians.

PMID- 23126042
TI  - [Antiaggregation therapy after percutaneous coronary intervention in a patient
      with thrombocytopenia: case report].
AB  - Dual antiaggregation (antiplatelet) therapy is mandatory in patients having
      received a stent during percutaneous coronary intervention. This therapy usually
      consists of acetylsalicylic acid (100 mg per day) and clopidogrel (75 mg per day)
      for at least 6 to 12 months (depending on the type of stent). Such therapy has
      been shown to reduce significantly unwanted clinical events, although slightly
      increasing the risk of bleeding. Coronary stents must rarely be implanted in
      patients who have or develop thrombocytopenia. In such patients, the risk of
      bleeding is increased manifold. On the other hand, the risk of potentially fatal
      thrombotic events is unknown. In this case report, we present a patient who
      developed thrombocytopenia shortly (one month) after the stent had been
      implanted. After thorough clinical workup, we could not find the remediable cause
      of thrombocytopenia. Because of the potential of acetylsalicylic acid to induce
      thrombocytopenia, it was excluded from therapy and a double dose of clopidogrel
      (150 mg per day) was introduced. Then we decided to evaluate platelet function
      with the ADP aggregation test (which indicates the degree to which the function
      of platelets is blocked by clopidogrel) and aspirin resistance test (which
      indicates the degree to which the function of platelets is blocked by
      acetylsalicylic acid). In the first set of tests, the patient was shown to be
      hyperreactive to both substances. We then lowered the dose of clopidogrel to the
      standard dose and evaluated the function of platelets with the same tests two
      weeks later and the results were the same. Because the patient was without
      obvious and laboratory signs of bleeding, we decided not to change the prescribed
      antiplatelet therapy because of fear from potentially fatal thrombotic events.
      The use of dual antiplatelet therapy in patients with thrombocytopenia is
      particularly challenging. We believe that in such patients, firstly, the cause of
      thrombocytopenia should be sought for by thorough clinical investigation. If not
      found, as in our patient, tailoring of such therapy should be done using
      currently available aggregation tests. In such a way, patients could be protected
      from both excessive bleeding and potentially devastating thrombotic events.
      Unfortunately, this is a sole example and definite conclusions could only be made
      on larger studies.

PMID- 23126043
TI  - [Clear cell carcinoma of the endometrium confined to atrophic endometrial polyp-
      case report].
AB  - Clear cell carcinoma is a rare form of endometrial carcinoma inline type II
      estrogen-independent. It accounts for only 1% to 5.5% of all endometrial
      carcinomas. It is usually detected in postmenopausal women, who are older than
      those with endometrioid carcinoma. Clear cell carcinoma may exhibit solid,
      papillary, tubular and cystic patterns. The malignant cells are characterized by
      a moderate amount of clear or foamy cytoplasm; however, its recognition as a
      clear cell type of cancer cytologically is not often possible. The tumor is
      usually poorly differentiated, tends to be high grade, with deep myometrial
      invasion, lymphovascular space invasion, and metastasis in pelvic lymph node.
      That is why this tumor has a poor prognosis, as in our case of a 72-year-old
      woman with symptoms of deficient uterine bleeding. In a period of two months, two
      suction endometrial curettages were performed. The material obtained by
      endometrial curettage for histopathologic verification was very scanty. The
      assessment described an inactive endometrium with degenerative epithelial cells
      in scanty necrotic background. Direct endometrial samples with uterobrush yielded
      a finding of atypical epithelial cells of open etiology with dense chromatin and
      prominent nucleoli, also with foam cell histiocytes and old blood in the
      background. Cytologic diagnosis of intraepithelial lesion, possible
      adenocarcinoma was made. Ultrasonography of the uterus was suspect of neoplasm.
      After surgery, the pathologic diagnosis of endometrial clear cell carcinoma was
      made. It was a rare case of aggressive type of endometrial carcinoma confined to
      an atrophic endometrial polyp. In conclusion, we might say that direct
      endometrial sample can provide accurate diagnosis of endometrial tumor,
      especially when the endometrial tumor is a small one, thus saving time for
      diagnostic testing. This is based on the potential of cytology to make malignant
      diagnosis possible even with a few tumor cells on the slide.

PMID- 23126044
TI  - [Hepatocellular carcinoma initially diagnosed by fine needle aspiration cytology
      of the pelvic bone metastasis].
AB  - Hepatocellular carcinoma mostly develops in patients with liver cirrhosis due to
      chronic hepatitis C virus (HCV) infection. A case is presented of a patient with
      hepatorenal syndrome as a sequel of liver cirrhosis due to HCV infection. Primary
      tumor of the liver was not diagnosed by routine procedures, but by fine needle
      aspiration cytology of the extensive osteolytic lesion of the pelvic bone,
      performed as part of the pre-transplantation workup. Transplantation procedure
      was abandoned because of inappropriate donor liver (hepatic artery thrombosis),
      and palliative pain-relieving irradiation was recommended. However, hepatic coma
      developed very rapidly and the patient died within a month of the diagnosis of
      metastatic hepatocellular carcinoma. Although hepatocellular carcinoma metastases
      are not rare, massive bone infiltration from a primary tumor undetectable by
      routine methods is not frequently encountered.

PMID- 23126045
TI  - [Multifocal epithelioid hemangioendothelioma treated by liver transplantation-
      case report].
AB  - Multifocal epithelioid hemangioendothelioma of the liver is a rare primary tumor
      with a variable course of disease. A case is presented of a 27-year-old female
      patient with multiple hepatic lesions on ultrasonography, suspect of metastatic
      tumor of the liver. Serum tumor markers were not elevated, while clinical
      examination of the lungs, gastrointestinal and gynecologic systems did not
      confirm the presence of a primary tumor process. Metastatic tumor and primary
      hepatocellular tumor were ruled out by fine needle aspiration cytology. Along
      with a characteristic immunophenotype of the vascular cell endothelium (positive
      for CD31 and CD34), high proliferation demonstrated by the analysis of
      argyrophilic nucleolar organization regions (AgNOR) and DNA aneuploidy,
      cytomorphological pattern suggested the diagnosis of angiosarcoma.
      Histopathologic finding corresponded to epithelioid hemangioendothelioma. Ten
      years after orthotopic liver transplantation, the patient is free from disease
      relapse, with regular follow up testing. Hemangioendothelioma of the liver is
      characterized by multifocality, which excludes resection; thus, liver
      transplantation is the method of choice. Therefore, preoperative diagnostic
      workup is of utmost importance to differentiate it from other primary and
      metastatic tumors of the liver.

PMID- 23126046
TI  - [Preoperative diagnosis of fallopian tube carcinoma by cytology].
AB  - Carcinoma of the fallopian tube is a rare, extremely aggressive neoplasm that is
      uncommonly diagnosed in early stages of the disease. We present a case of a 56
      year-old nulliparous patient with tubal carcinoma stage Ic (FIGO).
      Preoperatively, the only suspect finding were atypical glandular cells of
      extrauterine origin presented on a routine Papanicolaou smear. Histopathologic
      finding of D&C implicated the same suspicion of extrauterine genital malignancy.
      After hysterectomy with bilateral adnexectomy and omentectomy, histopathology
      confirmed stage I primary adenocarcinoma of the right fallopian tube
      (alveomedullary type) with positive intraoperative cytology of Douglas pouch
      lavage. As the patient had bilateral occlusion of the tubes, we presumed that
      tumor cells were leaking through the uterus into the vagina, and we were luckily
      alerted within the pathological cervical smear to the possible presence of a
      malignancy in the abdomen. The patient received 6 courses of cyclophosphamide and
      cisplatin chemotherapy postoperatively. Two years after the diagnosis, the
      patient is healthy, without a trace of primary malignant disease. Cytology
      undoubtedly plays a vital role as a screening tool in the detection of
      premalignant and malignant diseases of the female genital tract, particularly
      lesions in the uterine cervix. However, its role in clinical staging of
      gynecologic diseases should not be underestimated either, due to its ability to
      detect malignant epithelial cells in peritoneal samples as well as for its
      detecting and diagnostic value in other malignant gynecologic diseases.

PMID- 23126047
TI  - [Extramedullary multiple myeloma of the colon--case presentation and literature
      review].
AB  - Multiple myeloma with gastrointestinal infiltration is rare, and it has been
      usually described in some case reports or case series. Stomach and small
      intestine are mostly involved, while large bowell involvement is very rare.
      Multiple myeloma should be considered in the differential diagnosis of some other
      diseases of the large bowel associated with weight loss, diarrhoea,
      malabsorption, frequent lumbar pain, effort intolerance. Colonoscopic biopsy
      followed by histopathological examination is essential for the diagnosis of
      multiple myeloma. Multiple myeloma with extramedullary infiltration of the colon
      has no well defined treatment guideline. Localised infiltration of
      gastrointestinal tract could be treated by surgical resection, but as these
      tumors are radiosensitive, radiotherapy has also been used. Chemotherapy with
      pulsed dexamethasone and afterwards a combination of cyclophosphamide,
      vincristine, melphalan and prednisone has been described in some case studies.
      Some patients were treated with other therapies incuding thalidomide, bortezomib,
      autologous or allogeneic stem cell transplantation. The clinical presentation,
      diagnosis and therapy may be challenging, so we present a 66-year old patient
      with extramedullary multiple myeloma of the colon who was treated at our
      Department.

PMID- 23126048
TI  - [Multiple myeloma in a patient with chronic lymphocytic leukemia--case report and
      literature review].
AB  - The occurrence of B-cell chronic lymphocytic leukemia (B-CLL) and another B-cell
      neoplasm in the same patient is a rare event and is mostly described in the
      literature as single case reports. In most cases reported in the literature, CLL
      was diagnosed several years before multiple myeloma. Some patients were only
      observed for CLL without therapy, whereas others had already been treated for CLL
      when the diagnosis of myeloma was established. Some authors came to a conclusion
      that therapy used for treating CLL can induce some secondary neoplasms, like
      multiple myeloma. We present a male patient who was diagnosed with multiple
      myeloma 11 years after B-CLL had been diagnosed. Two hematologic neoplasms in one
      patient could be a diagnostic problem, but also a therapeutic challenge.

PMID- 23126049
TI  - [Acute renal failure as first manifestation of B-CLL].
AB  - In December 2005, the 55-year-old patient was hospitalized because of acute
      kidney failure and suspected hemorrhagic fever. The physical examination showed
      splenomegaly (spleen ultrasound-18 cm in large diameter, and 11 cm by palpation)
      with thrombocytopenia and anemia. He underwent kidney biopsy which described
      infiltration of small B cell lymphocytes with positive lambda chains. His bone
      marrow showed infiltration of atypical lymphocytes, and flow cytometry was
      typical of B-cell CLL. Patient started therapy with corticosteroids
      (methylprednisolone 80 mg iv) and continued treatment with prednisone (Decortin
      20 mg tablets) and chlorambucil (Leukeran 16 mg tablets) through three days. An
      addition to therapy lead to an increase in platelet count, creatinine level
      decline and recovery of renal function was observed. He was treated with 6 cycles
      of therapy with prednisone and chlorambucil and achieved a satisfactory
      therapeutic effect with adequate hematologic parameters and less severe
      splenomegaly. Maintenance therapy was continued with prednison at daily dose of
      10 mg. Our patient is one of the amongst previously reported as an example of a
      rare complication of CLL'with leukemic infiltrate causing acute renal
      insufficiency. Renal biopsy is necessary to confirm the diagnosis. This
      complication appears to respond well to a variety of treatments. Our patient
      achieved complete resolution of renal failure and partial hematological response
      with combination of chlorambucil and prednisone.

PMID- 23126050
TI  - [Erythroblasts in the peripheral blood of adult patient as an adverse prognostic
      sign--a case report].
AB  - Red blood cells (RBC) normally lose their nuclei before appearing in peripheral
      blood. After having undergone differentiation in bone marrow, blood cells must
      cross the blood-marrow barrier to enter the bloodstream. Erythroblasts, or
      nucleated red blood cells (NRBC), do not distort easily, so they cannot escape
      this barrier. Therefore, with the exception of the neonatal period, the presence
      of NRBCs in peripheral blood is always a pathologic finding. NRBCs may be found
      in the course of severe diseases and are associated with poor prognosis and
      higher mortality. The underlying pathophysiology of NRBCs in peripheral blood is
      not fully understood. It is hypothesized that their appearance could be provoked
      by either increased erythropoiesis or bone marrow micro-architectural damage
      mostly caused by inflammation and/or decreased tissue oxygenation. In addition,
      it is known that the mortality is higher in NRBC-positive patients as compared
      with NRBC-negative patients. Hereby we present a patient admitted to the hospital
      with the symptoms of cardiac failure and decompensated liver cirrhosis. The
      patient was already known to have liver cirrhosis of ethylic etiology, cardiac
      decompensation caused by hypertensive heart disease with permanent atrial
      fibrillation, chronic obstructive pulmonary disease, diabetes mellitus type 2,
      and cholelithiasis. During hospital stay, the patient developed acute
      pancreatitis and, soon after that, a stroke with left hemiparesis followed by
      cardiopulmonary arrest. Then he was transferred to the intensive care unit.
      Despite appropriate therapy, intensive care treatment and cardiopulmonary
      support, the patient's general state worsened, he developed multiple organ
      failure and died on day 10 of intensive care unit stay. Three days earlier, NRBCs
      were detected in peripheral blood and their concentration increased during the
      next two days before death. NRBCs are known to appear 1-3 weeks before death, but
      their appearance does not seem to be related to one particular cause of death.
      Still, detection of NRBCs is an independent risk of poor outcome, where the
      mortality increases with the increasing NRBC concentration. Detection of NRBCs in
      blood is a relatively early phenomenon prior to death, so screening for NRBCs may
      aid in the early identification of patients at high risk, and in making duly
      decision for NRBC-positive patients to obtain ongoing intensive care treatment.

PMID- 23126051
TI  - [Needle tract seeding of hepatocellular carcinoma after liver transplantation].
AB  - Ultrasound guided fine needle aspiration cytology (FNAC) and core needle biopsy
      (CNB) are effective methods for the diagnosis of focal hepatic lesions. In case
      of neoplastic lesions, however, this may be followed by the seeding of malignant
      cells along the needle tract. We report a case of subcutaneous needle tract
      seeding of hepatocellular carcinoma (HCC) 25 months after liver transplantation.
      A 57-year-old man with compensated hepatitis-B-related liver cirrhosis was
      diagnosed with HCC by CNB, and the lesion was resected. Ten months after the
      procedure, FNAC of a small hepatic lesion confirmed tumor recurrence. The patient
      was successfully transplanted and 25 months later, a subcutaneous tumor appeared
      on the abdominal wall over the previous site of puncture without further
      dissemination of the disease. Total resection of the lesion confirmed HCC. It
      remains undetermined whether the seeding appeared after FNAC or CNB. After 18
      month follow-up the patient was uneventful. The objectives of this report are to
      present clinical aspects and outcome of HCC needle tract seeding in a
      transplanted patient, discussing the problems and pitfalls of diagnostic workup
      and management of HCC.

PMID- 23126052
TI  - [Longterm indolent course of pleomorphic mantle cell lymphoma with multiple
      chromosomal abnormalities].
AB  - Mantle cell lymphoma (MCL) is a B-cell neoplasm characterized by aggressive
      clinical course with an average 3- to 5-year patient survival. We present a
      patient whose illness turned from initial classical morphological variant to a
      more aggressive pleomorphic form of MCL in only a few months, but with unchanged
      long-term indolent clinical course. At the time when lymphoid cell pleomorphism
      was proven, the disease presented itself through recurrent peripheral
      lymphadenopathy without extranodal involvement or general symptoms. Other
      numerous abnormalities were found next to typical cytogenetic translocation t
      (11,14). Histopathology confirmed the diagnosis of MCL, pleomorphic type. After
      autologous stem cell transplantation, the disease remained morphologically the
      same, but the patient was in a good general condition for a long period of time.
      More than two years after the pleomorphic MCL had been diagnosed and one year
      after the transplantation, major lymphadenopathy occurred. Our case report points
      to a large spectrum of morphological and cytogenetic variability of MCL, which
      often does not correlate with the clinical course of the disease.

PMID- 23126053
TI  - [Disseminated aspergillosis in a patient with simultaneous pancreas and kidney
      transplant].
AB  - A 31-year-old woman suffering from diabetes type1 and terminal kidney disease,
      with simultaneously transplanted kidney and pancreas, developed an episode of
      acute organ rejection caused by antibodies. The management of organ rejection was
      complicated by cytomegalovirus viremia, with accompanying leukopenia and
      neutropenia. The patient also developed invasive aspergillosis of the lungs,
      which progressed and disseminated hematogenously to the thyroid gland and the
      skin. Due to resistance to classical antimycotic therapy, the patient was treated
      with a combination of caspofungin and variconazole. In the beginning of
      treatment, the effects of this combined therapy were not evident due to strong
      immunosuppression caused by antimycotic immunoglobulin, which the patient had
      been administered on her previous hospital stay to treat acute kidney transplant
      rejection caused by antibodies, as well as due to immunosuppression caused by
      tacrolimus, mycophenolate mofetil and prednisone. On combined therapy with
      antimycotic drugs and supportive therapy, the patient was completely cured.

PMID- 23126054
TI  - [Billateral pleural effusion as first manifestation of multiple myeloma].
AB  - Multiple myeloma is clonal malignancy of plasma cells with overproduction of
      monoclonal antibodies and destruction of bones. Hypercalcemia, anemia and renal
      disfunction are common manifestations of the disease. Billateral pleural effusion
      is rare multiple myeloma presentation with unfavorable prognosis so it is
      important to recognizze it for better diagnostic and therapy approach. 59-year
      old woman was admitted to Hematology Department with history of severe caugh,
      dyspnea and left chest pain. Physical examination and chest X-ray showed
      billateral pleural effusion while cytologic examination of pleural aspirate found
      plasma cells. Bone marrow examination and skeleton X-ray confirmed diagnosis of
      multiple myeloma. Serum and urine immunoelectrophoresis detected lambda Bence
      Jones protein. This case is rare manifestation of multiple myeloma.

PMID- 23126055
TI  - [Pleural mesothelioma--case report].
AB  - Pleural mesothelioma is a rare neoplasm with the incidence of 1-2 per million
      people. The incidence is higher in male population (10-30/million), whereas the
      incidence in female population is 2 per million. It occurs predominantly at older
      age (65+ years). The most common clinical manifestation of pleural mesothelioma
      is pleural effusion with dyspnea, which makes it a diagnostic problem since many
      cardiac diseases can have the same presentation. We report a case of pleural
      mesothelioma in an 80-year-old woman that presented with dyspnea and pleural
      effusion, which was at first considered as a sign of heart failure. Clinical
      presentation also included metabolic disorders and deep vein thrombosis, and the
      patient's epidemiologic history was negative, so diagnostic procedures including
      pleurocentesis were directed towards detection of the possible malignant disease.
      Cytologic analysis followed by biopsy pointed to the diagnosis of pleural
      mesothelioma. Persistent pleural effusions that do not coincide with cardiac
      disease, especially if accompanied by metabolic disorders and paraneoplastic
      syndromes, require additional diagnostic workup to identify the etiology of
      pleural effusion.

PMID- 23126056
TI  - [Secondary (AA) renal/bone amyloidosis complicating rheumatoid arthritis].
AB  - Amyloidosis is a clinical entity that results from deposition of an extracellular
      protein material that causes disruption in normal architecture and impairs
      function of multiple organs and tissues. Secondary amyloidosis (AA) is a rare but
      serious complication that appears in the context of cancer, chronic inflammation,
      and chronic infectious disease, including rheumatoid arthritis. Renal failure is
      the most common clinical presentation of AA, ranging from nephrotic syndrome and
      impaired renal function to renal failure, with a potential for high morbidity. We
      present a case of a 52-year-old female patient diagnosed with rheumatoid
      arthritis at age 27. She was hospitalized due to worsening clinical condition.
      Physical examination revealed marked peripheral edema in both lower extremities.
      Laboratory tests showed an increase of inflammatory reactants, anemia,
      electrolyte disbalance, and severe hypoalbuminemia and hypoproteinemia. She had
      proteinuria 15.4 g/24 h and renal function estimated by creatinine clearance was
      78 mL/min, within the second degree of chronic kidney disease. Renal biopsy was
      performed for evaluation of renal insufficiency with nephrotic range proteinuria.
      Congo red staining showed the presence of characteristic amyloid deposits that
      immunoreacted with the antibody against amyloid A protein, thus confirming the
      diagnosis of secondary amyloidosis.

PMID- 23126057
TI  - [Hyperhaemolytic siyndrome in patient without haemoglobinopathies].
AB  - Hyperhemolysis syndrome usually occurs in patients with sickle cell disease and
      possibly thalassemia who receive multiple transfusions. There are only few
      clinical reports on patients without hemoglobinopathies as in this report. Our
      patient was diagnosed with hyperhemolytic reaction and was infused with IVIG and
      methylprednisolone for several days. Signs of tissue hypoxia developed along with
      increased cardiac enzymes, hepatocellular and cerebrovascular injury, and finally
      death. On autopsy, there was no evidence for hemolytic uremic syndrome or
      thrombotic thrombocytopenic purpura.

PMID- 23126058
TI  - [Primary ovarian malignant mixed mesodermal tumor (MMMT) as a second primary
      tumor in a patient with invasive breast carcinoma--case report].
AB  - Malignant mixed mesodermal tumor (MMMT) of the ovary is a rare aggressive tumor
      that consists of an epithelial (carcinoma) and a stromal (sarcoma) component.
      MMMT accounts for less than 2% of ovarian cancers and has a very poor prognosis.
      We present a case and difficulties of diagnosing an ovarian MMMT in a
      postmenopausal woman with a history of invasive breast carcinoma treated
      postoperatively with radiotherapy and tamoxifen. A 52-year-old patient presented
      with unilateral ovarian tumor and moderately elevated CA125 (107 U/mL) and
      underwent laparotomy. Fine needle aspiration of the ovary and ascites for
      cytologic analysis, and tumor biopsy for histopathology were performed
      intraoperatively. Intraoperative cytologic sample showed necrotic background with
      rare single malignant cells with pale, abundant cytoplasm and conspicuous
      nucleoli suggesting clear cell carcinoma. Ascites sample showed inflammatory and
      reactive background with suspected papillary formations mimicking adenocarcinoma.
      Postoperatively, cytochemical PAS staining and immunocytologic staining with
      epithelial antigen (EA), cytokeratin (CK)7 and vimentin showed EA and PAS
      positivity for ovarian tumor, and EA and CK7 for ascites, suggesting a clear cell
      carcinoma. Histology revealed ovarian clear cell carcinoma. Three months later,
      the patient underwent hemicolectomy because of tumors on the right large bowel
      serosa with intraoperative morphological finding of metastatic malignant tumor
      without other specific features. Postoperative morphological analysis and
      immunohistochemical staining of the tumor revealed two malignant components,
      epithelial and stromal one. Repeat histologic analysis of the ovarian tumor
      confirmed ovarian MMMT (with a clear cell carcinoma component). Other studies of
      breast cancer emphasize that patients with invasive breast cancer and mutations
      of BRCA1 and BRCA2 genes are at an increased risk of primary ovarian cancer. Our
      study confirmed it and suggested considering a second primary malignant tumor of
      ovarian origin in patients with a history of breast carcinoma, postoperatively
      treated with radiotherapy and tamoxifen. Although rare, second primary ovarian
      tumors may present as MMMT.

PMID- 23126059
TI  - [The history and definition of inflammatory bowel diseases].

PMID- 23126060
TI  - [Recent advances in the immunopathogenesis of inflammatory bowel diseases].

PMID- 23126061
TI  - [Progress and prospect of inflammatory bowel disease diagnostics].

PMID- 23126062
TI  - [Recent advances and future goals in the treatment of inflammatory bowel
      diseases].

PMID- 23126063
TI  - [Recent progress in surgical treatment of IBD].

PMID- 23126064
TI  - [Descriptive epidemiology of inflammatory bowel disease in Japan].

PMID- 23126065
TI  - [Familial prevalence of inflammatory bowel disease].

PMID- 23126066
TI  - [Natural history and prognosis of inflammatory bowel diseases].

PMID- 23126067
TI  - [Risk factors for inflammatory bowel disease].

PMID- 23126068
TI  - [Mechanism of pathogenesis of inflammatory bowel diseases].

PMID- 23126069
TI  - [Genetics of inflammatory bowel disease].

PMID- 23126070
TI  - [Etiology of inflammatory bowel disease--lifestyle and environmental risk
      factors].

PMID- 23126071
TI  - [Dysbiosis in inflammatory bowel disease].

PMID- 23126072
TI  - [Contribution of intestinal macrophage to gut immune homeostasis and its
      disruption in inflammatory bowel disease].

PMID- 23126073
TI  - [Innate and acquired immunity in inflammatory bowel disease].

PMID- 23126074
TI  - [Roles of inflammatory mediators and cytokines in the pathogenesis of
      inflammatory bowel disease].

PMID- 23126075
TI  - [Involvement of lymphocyte homing and adhesion molecules].

PMID- 23126076
TI  - [Nervous and endocrine aspects of inflammatory bowel disease].

PMID- 23126077
TI  - [Role of blood flow and microcirculation disturbance in inflammatory bowel
      disease].

PMID- 23126078
TI  - [Mechanism of mucosal regeneration in inflammatory bowel disease].

PMID- 23126079
TI  - [Animal experimental models for inflammatory bowel diseases].

PMID- 23126080
TI  - [Diagnostic criteria of ulcerative colitis].

PMID- 23126081
TI  - [Diagnostic criteria for Crohn disease].

PMID- 23126082
TI  - [Clinical course of ulcerative colitis].

PMID- 23126083
TI  - [Natural history and disease progression of Crohn's disease].

PMID- 23126084
TI  - [Classifications and activity indexes of ulcerative colitis].

PMID- 23126085
TI  - [Classification of Crohn's disease].

PMID- 23126087
TI  - [Diagnostic process of inflammatory bowel disease].

PMID- 23126086
TI  - [Differential diagnosis of ulcerative colitis and Crohn's disease].

PMID- 23126088
TI  - [Clinical features of inflammatory bowel disease].

PMID- 23126089
TI  - [Blood test and bacteriological examination in diagnosis and prognostic
      prediction of inflammatory bowel disease].

PMID- 23126090
TI  - [Disease-specific biomarkers of inflammatory bowel disease].

PMID- 23126091
TI  - [Recent advance of diagnostic tools for patients with inflammatory bowel
      disease].

PMID- 23126092
TI  - [Radiographic examination of inflammatory bowel disease].

PMID- 23126093
TI  - [Colonoscopy in the practice of inflammatory bowel diseases].

PMID- 23126094
TI  - [Usefulness of videocapsule endoscopy and double-balloon endoscopy for small
      bowel lesions of patients with inflammatory bowel disease].

PMID- 23126095
TI  - [Diagnosis of inflammatory bowel disease by computed tomography and magnetic
      resonance imaging].

PMID- 23126096
TI  - [Imaging in inflammatory bowel disease: ultrasound and computed tomography (CT
      enterography/colonography)].

PMID- 23126097
TI  - [Pathological diagnosis and differential diagnosis of Crohn's disease and
      ulcerative colitis].

PMID- 23126098
TI  - [Indeterminate colitis-concept and clinical treatment].

PMID- 23126099
TI  - [Esophagogastroduodenal mucosal lesions in patients with inflammatory bowel
      disease].

PMID- 23126100
TI  - [Anorectal lesions in inflammatory bowel disease].

PMID- 23126101
TI  - [Extraintestinal complications of inflammatory bowel disease].

PMID- 23126102
TI  - [Clinical characteristic of inflammatory bowel disease in the elderly].

PMID- 23126103
TI  - [Therapeutic strategy for ulcerative colitis].

PMID- 23126104
TI  - [Therapeutic strategy for Crohn's disease].

PMID- 23126105
TI  - [Treatment strategy for severe and refractory inflammatory bowel disease].

PMID- 23126106
TI  - [A treatment indicator revision plan of the ulcerative colitis].

PMID- 23126107
TI  - [Guidelines for treatment of Crohn's disease].

PMID- 23126108
TI  - [5-Aminosalicylate derivatives].

PMID- 23126109
TI  - [Corticosteroid].

PMID- 23126110
TI  - [Immunomodulator: azathioprine and 6-mercaptopurine].

PMID- 23126111
TI  - [Effect of immunosuppressants on inflammatory bowel disease: tacrolimus and
      cyclosporine].

PMID- 23126112
TI  - [Anti tumor necrosis factor alpha antibody: infliximab].

PMID- 23126113
TI  - [Anti-TNF alpha antibody: adalimumab].

PMID- 23126114
TI  - [Topical therapy].

PMID- 23126115
TI  - [Antibiotics for inflammatory bowel disease].

PMID- 23126116
TI  - [Clinical efficacy and indications of leukocytic cytapheresis in inflammatory
      bowel disease].

PMID- 23126117
TI  - [Dietary therapy and nutritional therapy for inflammatory bowel disease].

PMID- 23126118
TI  - [Efficacy of probiotics in inflammatory bowel disease].

PMID- 23126119
TI  - [Kampo therapy for inflammatory bowel diseases].

PMID- 23126120
TI  - [Psychosomatic approaches to inflammatory bowel disease].

PMID- 23126121
TI  - [Current status of new drug development for inflammatory bowel diseases].

PMID- 23126122
TI  - [Balloon dilatation for intestinal stricture in Crohn's disease].

PMID- 23126123
TI  - [Anti-viral therapy for ulcerative colitis complicated with cytomegalovirus
      colitis].

PMID- 23126124
TI  - [Chemoprevention of colorectal cancer associated with IBD].

PMID- 23126125
TI  - [Practical management and medical treatment for inflammatory bowel disease during
      pregnancy].

PMID- 23126126
TI  - [Intestinal manifestations of inflammatory bowel disease].

PMID- 23126127
TI  - [Extraintestinal complications of inflammatory bowel disease].

PMID- 23126128
TI  - [Strategy of surgical treatment for inflammatory bowel disease].

PMID- 23126129
TI  - [Surgical indication and treatment for ulcerative colitis].

PMID- 23126130
TI  - [Operative indication and problem in Crohn's disease].

PMID- 23126131
TI  - [Indication and problems of laparoscopic surgery for ulcerative colitis and
      Crohn's disease].

PMID- 23126132
TI  - [Treatment for perianal Crohn's disease].

PMID- 23126133
TI  - [Clinical course and complications of fecal diversion for the patients with
      Crohn's disease].

PMID- 23126134
TI  - [Diagnosis and management of pouchitis].

PMID- 23126135
TI  - [Diagnosis and treatment for toxic megacolon].

PMID- 23126136
TI  - [Perioperative care for inflammatory bowel disease].

PMID- 23126137
TI  - [Long-term outcome of surgery for inflammatory bowel disease].

PMID- 23126138
TI  - [Epidemiology, statuses, and problems in children with IBD].

PMID- 23126139
TI  - [Diagnosis and clinical characteristics of pediatric inflammatory bowel disease].

PMID- 23126140
TI  - [Guidelines for treatment of inflammatory bowel disease in children].

PMID- 23126141
TI  - [Surgical indication and consideration for inflammatory bowel disease in
      children].

PMID- 23126142
TI  - [Carcinogenesis of ulcerative colitis and significance and practice of
      surveillance].

PMID- 23126143
TI  - [Intestinal cancer in patients with Crohn's disease].

PMID- 23126144
TI  - [Carcinogenesis in inflammatory bowel disease].

PMID- 23126145
TI  - [Magnifying endoscopy of neoplasm associated with ulcerative colitis].

PMID- 23126146
TI  - [Clinicopathological features and surgery of intestinal cancer associated with
      inflammatory bowel disease].

PMID- 23126147
TI  - [Surgery for rectal and anal canal cancer with ulcerative colitis].

PMID- 23126148
TI  - [Diagnosis and treatment for anal canal cancer and fistula-associated anal cancer
      in Crohn's disease].

PMID- 23126149
TI  - [Nutrition, diet therapy of inflammatory bowel disease].

PMID- 23126150
TI  - [Lifestyle guidance for inflammatory bowel disease patients].

PMID- 23126151
TI  - [Quality of life in the patients with inflammatory bowel disease].

PMID- 23126152
TI  - [Social support for inflammatory bowel disease patients].

PMID- 23126153
TI  - [Characteristic future of intestinal Behcet's disease and simple ulcer].

PMID- 23126154
TI  - [Intestinal tuberculosis].

PMID- 23126155
TI  - [Yersinia enterocolitis, Salmonella enterocolitis, Campylobacter enterocolitis].

PMID- 23126156
TI  - [Amebic colitis].

PMID- 23126157
TI  - [Cytomegalovirus enterocolitis].

PMID- 23126158
TI  - [Ischemic colitis].

PMID- 23126159
TI  - [Irritable bowel syndrome].

PMID- 23126160
TI  - [Antibiotic associated diarrhea (AAD)].

PMID- 23126161
TI  - [NSAIDs-induced intestinal mucosal injury].

PMID- 23126162
TI  - [APC (argon plasma coagulation) therapy of radiation colitis].

PMID- 23126163
TI  - [Nonspecific multiple ulcers of the small intestine].

PMID- 23126164
TI  - [Clinical characteristics of cases of primary sclerosing cholangitis associated
      with inflammatory bowel disease].

PMID- 23126165
TI  - [Practice guidelines for Crohn's disease and ulcerative colitis; features and
      application to clinical practice].

PMID- 23126166
TI  - [Genetic factors affecting elevated thiopurine sensitivity in Japanese patients
      with inflammatory bowel disease].

PMID- 23126167
TI  - [Incomplete synthesis of carbohydrate determinants in ulcerative colitis].

PMID- 23126168
TI  - [Genetic alterations leading to the development of colitis-associated colorectal
      cancers].

PMID- 23126169
TI  - [Dental students and research].

PMID- 23126170
TI  - [Stomach protection with use of NSAIDs 2].

PMID- 23126171
TI  - [Immediate treatment in apical radiolucency. Yes].

PMID- 23126172
TI  - [Immediate treatment in apical radiolucency. No].

PMID- 23126173
TI  - [Disciplinary board censures improper delegation].
AB  - A regional disciplinary board censured a dentist who allowed someone without
      proper authorisation to carry out a procedure and that judgement was the
      motivation for providing some clarification concerning the Dutch law. In the
      Netherlands, more than in most other countries, a relatively large amount of
      freedom is given to people who are not medical doctors to carry out dental
      procedures. This freedom does, however, have its limits and they are established
      in the law governing the registration of healthcare professionals (in the BIG
      register). The central requirement in this law is competence. In addition, the
      law makes a distinction, at the present time, among a group of healthcare
      providers who are authorised to carry out, independently, restricted treatments
      (dentists), a group of healthcare providers who are authorised to perform certain
      functions (dental hygienists), and a group who are not authorised. Provided they
      satisfy legal requirements, non-authorised individuals can also carry out
      restricted treatments. In the future, this system might be breached, in the sense
      that the requirementfor authorisation will lapse.

PMID- 23126174
TI  - [Scoliosis: review of types, aetiology, diagnostics, and treatment 1].
AB  - A scoliosis is a flexible or rigid deformity of the spine in the frontal plane.
      There are several types of scoliosis, each with specific characteristics. The
      most prevalent types are idiopathic, congenital, and neuromuscular scoliosis and
      scoliosis in adults. The aetiology is varied and largely undetermined. Essential
      components of diagnostics are patient history, physical examination, and
      radiographs. Treatment options are a conservative approach involving observation
      and follow-up, a conservative approach involving non-surgical treatment, and
      surgical treatment. Usually, idiopathic scoliosis causes no or only few
      complaints at a young age. Up to 35% of patients have a certain degree of back
      pain. The choice of a certain treatment is determined by the likelihood of
      progression of the spine deformity. The objective of brace treatment is
      preventing progression of the deformity. Important objectives of surgical
      treatment are preventing progression of the deformity and correcting the
      deformity with correction or preservation of physical equilibrium.

PMID- 23126175
TI  - [Odontogenic maxillary sinusitis based on overextension of root canal filling
      material].
AB  - In a 48-year-old woman and a 35-year-old man, a sinusitis maxillaris resulting
      from overextension of root canal filling material after an endodontic treatment
      ofa maxillary molar could be diagnosed through computed tomography. The woman
      complained of nasal congestion and in the man 2 radiopaque abnormalities in the
      maxillary sinus were discovered coincidentally. The corpora aliena were removed
      surgically. Root canal filling materials containing zinc oxide or hydrocortisone
      may cause aspergillosis of the maxillary sinus because they encountergrowth of
      Aspergillus species. In case ofmaxillary sinusitis, surgical removal of
      overextended root canal filling material from the maxillary sinus is indicated.
      No treatment consensus consists for cases without maxillary sinusitis symptoms.

PMID- 23126176
TI  - [A local gingival swelling which was based on a peripheral giant cell lesion].
AB  - A 29-year-old woman consulted her dentist about a localgingival swelling which
      bled during tooth-brushing and had been present for 1 year. In the differential
      diagnosis, epulis gravidarum, a peripheral giant cell lesion, and peripheral
      ossifying granuloma were considered. After surgical removal, histopathological
      examination revealed a peripheral giant cell lesion. The presence of a peripheral
      giant cell lesion requires thorough excochleation of the underlying bone. If the
      bone is cleaned thoroughly, recurrence is rare.

PMID- 23126177
TI  - [Oral medicine 1. Causes and clinical symptoms of dry mouth].
AB  - Healthcare providers do not always recognize dry mouth and the problems
      associated with it. The symptoms of dry mouth and the patterns of complaints
      associated with it are the feeling that the mouth is dry; foamy or very watery
      saliva; a red appearance of the mucosa under a denture and the excessive presence
      of remaining food particles on the mucosa or the denture. The most serious
      detrimental aspect of dry mouth complaints is a reduced secretion of saliva, but
      afeeling ofa dry mouth can also exist without an objectively assessed
      hyposalivation. The most important causes of dry mouth are the side effects
      ofmedications, systemic diseases, radiotherapy in the head and neck region and
      occasionally a psychiatric disorder. Early recognition of the symptoms and the
      establishment ofa precise diagnosis are essential for proper treatment and for
      optimizing the quality of life of the patient. Basic investigation consists of an
      extensive patient history, inspection of the head and neck region and the oral
      cavity, evaluation ofthefunctioning of the salivary glands, and, if necessary,
      additional investigations.

PMID- 23126178
TI  - [Unilateral condylar hyperactivity].
AB  - Unilateral condylar hyperactivity is a growth disorder which is characterised by
      a progressive asymmetry in the mandibula and in some cases also secondarily in
      the maxilla. Various forms are hemimandibular hyperplasia, hemimandibular
      elongation and a hybridform. In deciding on a plan of treatment, it is important
      to determine whether there is a question of continuous and/or excessive condylar
      activity, possibly with the help of a skeletal scintigraphy.

PMID- 23126179
TI  - [Effects of seedling quality on growth of Rehmannia glutinosa and oligosaccharide
      content].
AB  - OBJECTIVE: To study the effect of seedling quality on growth, yield and quality
      of Rehmannia glutinosa at harvest and build a basis for its GAP. METHOD: The
      seedling quality of R. glutinosa in main producing regions was surveyed to
      understand the current status of seedling quality. Field experiments with
      different varieties and seedling quality were conducted to measure dry matter
      accumulation with different growth of R. glutinosa and oligosaccharide content,
      and economic yield at harvest. RESULT: The seedling was randomly selected by
      farmers in R. glutinosa producing regions. Seedling quality could significantly
      improve on seedling emergence rate, and promote seedling growth, especially with
      early stage R. glutinosa, finally increase yield at harvest. At harvest, 63% and
      50% of yield with A and B seedling could be improved for variety of 85-5, and 50%
      and 47% of yield could be increased for variety of Beijing No. 1, compared to the
      C seeding. CONCLUSION: In cultivation, the seedlings with the diameter > 1.5 cm
      should be transplanted firstly.

PMID- 23126180
TI  - [Effect of endophytic fungi on expression amount of key enzyme genes in saponins
      biosynthesis and Eleutherococcus senticosus saponins content].
AB  - OBJECTIVE: To analyze the effect of endophytic fungi on expression amount of key
      enzyme genes SS (squalene synthase gene), SE (squalene epoxidase gene) and bAS
      (beta-amyrin synthase gene) in saponin biosynthesis and saponins content in
      Eleutherococcus senticosus. METHOD: Wound method was used for back meeting the
      endophytic fungi to E. senticosus. With GAPDH as internal control gene, the
      expression of key enzyme genes was detected by real time PCR method. E.
      senticosus saponins content was measured by spectrophotometry method. RESULT:
      When wound method back meeting P116-1a and P116-1b after 30 d, the expression
      content of SS improved significantly (P < 0.05), however the back meeting of P109
      4 and P312-1 didnt change the expression of SS. After that SS expression showed
      reduction-equality-reduction varying trend. Thirty days after back meeting P312
      1, the expression content of SE improved significantly (P < 0.05). Ninty days
      after back meeting P116-1b and P312-1, the expression content of SE improved
      significantly to 130%,161%, respectively (P < 0.05). After 120 d, back meeting
      four endophytic fungi, the expression of SE were significantly higher than the
      control (P < 0.05). Back meeting four endophytic fungi form 60 d to 120 d, the
      expression of bAS was significantly higher than the control (P < 0.05). The back
      meeting four endophytic fungi improved E. senticosus saponins content
      significantly (P < 0.05). CONCLUSION: Endophytic fungi P116-1a, P116-1b, P1094
      and P312-1 significantly effected the expression of key enzyme genes SS, SE and
      bAS and then affected E. senticosus saponins content. Among the genes, bAS was
      key target gene.

PMID- 23126181
TI  - [In vitro embryo culture of Epimedium wushanense].
AB  - OBJECTIVE: To study the in vitro embryo culture of Epimedium wushanense and
      provide scientific basis for large scale production of tissue culture. METHOD:
      Cullus and buds were induced from embryo of E. wushanense on a MS medium
      supplemented with different 2,4-D,6-BA, NAA, IBA. RESULT: The optimal
      compositions of medium that induced callus and buds from embryo were the MS
      medium supplemented with 2,4-D 2 mg x L(-1), IBA 2 mg x L(-1) and NAA 0.5 mg x L(
      1) and the MS medium supplemented with IBA 2 mg x L(-1) and 6-BA 0.5 mg x L(-1),
      respectively. The optimum medium for callus differentiation was MS + 6-BA 1 mg x
      L(-1) + NAA 0.5 mg x L(-1) + IBA 1 mg x L(-1), and MS +6-BA 1.0 mg x L(-1) + NAA
      0.5 mg x L(-1) for shoots proliferation. CONCLUSION: Using embryo as explants,
      the method of induction and culture of E. wushanense was established by the
      callus and buds, and the embryo of E. wushanense can be quickly propagated.

PMID- 23126182
TI  - [Quality classification standard of Aucklandia lappa seed].
AB  - OBJECTIVE: To establish a quality classification standard for Aucklandia lappa.
      METHOD: Seed purity, 1 000-grain weight, germination rate, water content of 37
      seed samples from different areas were measured, and seed external characters
      were observed. The cluster analysis was applied for establishment of the primary
      quality classification standard of A. lappa seed. RESULT: The seed quality
      grading of A. lappa was described as three grades. The seed quality of each grade
      should reach following requirements: for first grade seeds, seed germination rate
      > or = 85%, purity > or = 99%, 1 000-grain weight > or = 26.0 g, water content <
      or = 8.8%; for second grade seeds, seed germination rate > or = 70%, purity > or
      = 98%, 1 000-grain weight > or = 23.8 g, water content < or = 10%; for third
      grade seeds, seed germination rate > or = 50%, purity > or = 96%, 1 000-grain
      weight > or = 23.0 g, water content < or = 11%. CONCLUSION: This quality
      classification standard of A. lappa can be used as the quality control standard
      of A. lappa.

PMID- 23126183
TI  - [Effects of different light quality on growth, active ingredients and enzymes
      activitiesof Salvia miltiorrhiza].
AB  - OBJECTIVE: This study aimed to investigate the effects of different light quality
      on the growth, accumulation of active ingredients and enzymes activities of
      Salvia miltiorrhiza. METHOD: The seedlings of S. miltiorrhiza were treated by
      different light quality, and relative parameters were measured. The data was
      statistically processed. RESULT: Plant height was significantly decreased with
      supplemental blue light (WB), and the root length, root diameter, root fresh
      weight and root dry weight were significantly increased with supplemental red
      light (WR). Salvianolic acid B concentration in S. miltiorrhiza was highly
      increased by supplemental blue and red light, but tanshinone IIA concentration
      was not significantly affected by supplemental blue and red light. Enzymes
      activities of SOD, POD, PAL, TAT and PPO in S. miltiorrhiza were significant
      increased by supplemental blue light, and enzymes activities of POD, TAT and PPO
      were significant increased by supplemental red light. CONCLUSION: The root growth
      of S. miltiorrhiza was greatly promoted by supplemental red light (WR).
      Salvianolic acid B concentration in S. miltiorrhiza was highly increased by
      supplemental blue and red light. Enzymes activities of TAT and PPO in S.
      miltiorrhiza were significant increased by supplemental blue light and red light.

PMID- 23126184
TI  - [Comparison of leaf morphological characters among different major varieties of
      Rehmannia glutinosa].
AB  - OBJECTIVE: To provide theoretical evidences for the identification and selective
      breeding of different major varieties of Rehmannia glutinosa by comparing their
      leaf characters such as the shapes, non-glandular hairs and the size and density
      of stomata. METHOD: The length, width and the ratio of the length to the width of
      leaves were measured, and the density and length of the non-glandular hair, the
      density, size and density of the stomata in the epidermis were measured by
      scanning electron microscope. RESULT: The results showed that there were obvious
      differences in length, width and the ratio of the length to the width of leaves,
      the density and length of the non-glandular hair, the density and size of the
      stomata in the epidermis. CONCLUSION: The morphological characters of the leaves
      mentioned above may serve as the identification standards of major varieties of
      R. glutinosa.

PMID- 23126185
TI  - [Seed dormancy mechanisms of Pseudostellaria heterophylla and its germination
      characteristics].
AB  - OBJECTIVE: Seed dormancy mechanisms, breaking dormancy and the optimal
      germinating conditions were studied to improve reproductive efficiency and
      quality standard of Pseudostellaria heterophylla. METHOD: The P. heterophylla
      seeds were stratified into wettish sand for 65 days under the temperature of -2-3
      degrees C, embryo length and germination dynamic change of seeds were measured in
      prophase every other 10 days and in middle every other 5 days. The influences on
      seed germination and seedling growth under different temperatures, germination
      beds were investigated. RESULT: The P. heterophylla seeds embryo morphology was
      unchanged in stratification. The seeds could not germinate at stratification
      within the first 35 days. The germination rate and germination energy of seeds
      increased with the stratification time after 35 days. Germination rate,
      germination energy, plant height and fresh weight under the 10 degrees C were
      significantly higher than those under other temperatures. Germination rate,
      germination energy, plant height, fresh weight and dry weight of plant in sand
      bed were higher than those of plant in other beds, and seed mildew rate and
      abnormal seedling proportion of plant in sand bed were less than those of plant
      in other beds. CONCLUSION: The dormancy of P. heterophylla seeds is mainly the
      physiological post-maturation. The optimal germination conditions of seeds is 10
      degrees C the culture of sand. The dormancy was broke under -2-3 degrees C of
      wettish sand for 45-50 days in practice.

PMID- 23126186
TI  - [Preparation procedures of anti-complementary polysaccharides from Houttuynia
      cordata].
AB  - OBJECTIVE: To establish and optimize the preparation procedures of the anti
      complementary polysaccharides from Houttuynia cordata. METHOD: Based on the yield
      and anti-complementary activity in vitro, the conditions of extraction and
      alcohol precipitating process were optimized by orthogonal tests. The optimal
      condition of deproteinization was determined according to the results of protein
      removed and polysaccharide maintained. The best decoloring method was also
      optimized by orthogonal experimental design. RESULT: The optimized preparation
      procedures were given as follows: extract the coarse powder 3 times with 50 times
      volume of water at 90 degrees C for 2 hours every time, combine the extracts and
      concentrate appropriately, equivalent to 0.12 g of H. cordata per milliliter. Add
      4 times volume of 90% ethanol to the extract, allow to stand for 24 hours to
      precipitate totally, filter and the precipitate was successfully washed with
      anhydrous alcohol, acetone and anhydrous ether. Resolve the residue with water,
      add trichloroacetic acid (TCA) to a concentration of 20% to remove protein.
      Decoloration was at a concentration of 3% with activated carbon at pH 3.0, 50
      degrees C for 50 min. The above procedures above were tested 3 times, resulting
      in the average yield of polysaccharides at 4.03% (RSD 0.96%), the average
      concentrations of polysaccharides and protein at 80.97% (RSD 1.5%) and 2.02% (RSD
      2.3%), and average CH50 at 0.079 g x L-(-1) (RSD 3.6%). CONCLUSION: The
      established and optimized procedures are repeatable and reliable to prepare the
      anti-complementary polysaccharides with high quality and activity from H.
      cordata.

PMID- 23126187
TI  - [Effect of Zingiber offiicinale and Aconitum cainichaeli before and after
      compatibility on contents of four gingerols].
AB  - OBJECTIVE: To discuss the synergistic mechanism of compatible use of two
      medicinal herbs, Zingiber offiicinale and Aconitum cainichaeli, by determining
      single decoction of Z. offiicinale and four gingerols (6-gingerol, 8-gingerol, 6
      shogaol, 10-gingerol) contained in compound decoction of Z. offiicinale and A.
      cainichaeli of different compatibility ratio using HPLC. METHOD: Kromasil-C18
      column (4.6 mm x 250 mm, 5 microm) was adopted. The mobile phase was acetonitrile
      (B) and 0.1% aqueous acetic acid (A) for gradient elution (0-30 min, 40%-90% B;
      30-35 min, 90%-40% B). The flow rate was 1.0 mL x min(-1). The detection
      wavelength was set at 275 nm. The column temperature was 30 degrees C. RESULT:
      The four gingerols were in baseline separation, with a good linearity (r >
      0.999), an average recovery of 100.9% -103.5% and RSD < 3.0%. Compared with the
      single decoction of Z. offiicinale, the content of gingerols in the compound
      decoction of Z. offiicinale and A. cainichaeli was on the rise and in direct
      proportion with the increase in the volume of A. cainichaeli. CONCLUSION: The
      synergistic mechanism of the compatibility of Z. offiicinale and A. cainichaeli
      can be proved with the increased release of gingerols from Z. offiicinale.

PMID- 23126188
TI  - [Study on intestinal absorption kinetics of gambogic acid in rats].
AB  - OBJECTIVE: To investigate the intestinal absorption kinetics of gambogic acid
      (GA) in rats. METHOD: In situ single-way intestinal perfusion model was
      established to study the intestinal absorption kinetics of GA in different
      absorption segments, and the concentration of GA in the perfusate was determined
      by HPLC. The effect of drug concentrations on intestinal absorption was also
      detected. RESULT: GA showed a higher absorption rate than other intestinal
      segments (P < 0.05) and kept unchanged in duodenum after addition in drug
      concentration. CONCLUSION: GA can be absorbed in all intestinal segments in rats
      with the higher absorption rate in duodenum. Its mechanism is passive diffusion.

PMID- 23126189
TI  - [Influence of different processing techniques of massa medicata fermentata on
      their amylase activity].
AB  - OBJECTIVE: To optimize different processing techniques of Massa Medicata
      Fermentata. METHOD: Single factor test was adopted, with the amylase activity of
      Massa Medicata Fermentata as the assessment indicator, to observe the influence
      of such factors as fermentation time and mixture techniques of active
      pharmaceutical ingredients on the amylase activity of Massa Medicata Fermentata.
      Meanwhile, Massa Medicata Fermentata prepared with the optimum processing
      techniques and superior and inferior products of Massa Medicata Fermentata in the
      market were compared in amylase activity, soluble starch content and soluble
      polysaccharide content. RESULT: The optimum fermentation time was 7 days. Adzuki
      bean shall be boiled before mixed with other materials. Artemisia annua,
      Polygonum hydropiper and Cocklebur grass shall be evenly mixed water decoction.
      The amylase activity, the soluble starch content and the soluble polysaccharide
      content of fermented Massa Medicata Fermentata could reach to 49.372 mg x min(-1)
      x g(-1), 7.967%, and 16.65% respectively, significantly higher than the two types
      of Massa Medicata Fermentata sold in the market. CONCLUSION: According to the
      optimum processing techniques, Adzuki beans were smashed and mixed equally with
      flour and Armeniacae Semen Amarum powder, and then successively added with A.
      annua, P. hydropiper and C. grass for even mixture. The fermentation time was 7
      days.

PMID- 23126190
TI  - [A new C-28 nortriterpenoid from fruits of Leonurus japonicus].
AB  - OBJECTIVE: To study the chemical constituents from the fruits of Leonurus
      japonicus. METHOD: The compounds were extracted by 70% methanol, then isolated
      and purified by column chromatography on silica gel, RP-18, Sephedax LH-20 and
      HPLC. Their structures were determined on the basis of spectroscopic data and
      physicochemical property. RESULT: Two 28-noroleanane-derived spirocyclic
      triterpenoids including a new acylated nortriterpenoid were isolated and
      identified as (17R)-19(18 --> 17)-abeo-2alpha,18beta,23-trihydroxy-3beta-E
      feruloyoxy-28-norolean-12-ene (1) and phlomistetraol B (2). CONCLUSION: Compound
      1 is a new compound,named as leonujaponin A. Both compounds 1-2 are isolated for
      the first time from Leonurus plants.

PMID- 23126191
TI  - [Non-anthraquinones constituents from the roots of Knoxia valerianoides].
AB  - Twenty-one non-anthraquinones constituents were isolated for the first time from
      an ethanol extract of the roots of Knoxia valerianoides by using a combination of
      various chromatographic techniques including column chromatography over silica
      gel, Sephadex LH-20, and reversed-phase HPLC. Their structures were identified by
      their physical-chemical properties and spectroscopic analysis including NMR and
      MS. The compounds include ten triterpenoids: ursolic acid (1), oleanolic acid
      (2), 2-oxo pomolic acid (3), pomolic acid (4), maslinic acid (5), rotungenic acid
      (6), tormentic accid (7), rotundic acid 3,23-acetonide (8), arjungenin (9), and
      2alpha, 3beta, 19alpha, 23-tetrahydroxy-urs-12-en-28-oic acid (10), four
      sitosterones: (24R)-24-ethylcholesta-4,22-dien-3-one (11), 3-oxo-4-en-sitosterone
      (12), 7-oxostigmasterol (13), and 7-oxo-beta-sitosterol (14), two lignans:
      eudesmin (15) and ciwujiatone (16), one coumarin: cnidilin (17), and four simple
      aromatic analogues: 5-hydroxymethylenefural (18), 3-hydroxy-4-methoxybenzoic acid
      (19), benzoic acid (20), and 2-hydroxy-5-methxoycinnamaldehydes (21). In the in
      vitro assays against human cancer cell lines (HCT-8, Bel7402, BGC-823, A549, and
      A2780), against deserum and glutamate induced PC12-syn cell damage, and against
      HIV-1 replication, and inhibiting protein tyrosine phosphatase 1B (PTP1 B), LPS
      induced NO production in macrophage, and Fe(2+)-cystine induced rat liver
      microsomal lipid peroxidation, at a concentration of 1 x 10(-5) mol x L(-1), no
      compound showed activity.

PMID- 23126192
TI  - [Constituents from the bark of Annona squamosa and their anti-tumor activity].
AB  - OBJECTIVE: To investigate the constituents of the Annona squamosa and evaluate
      their anti-tumor activity. METHOD: The compounds were isolated and purified by
      various column chromatography. Their structures were elucidated by spectral data
      analysis. Their anti-tumor activity was assayed by SRB method. RESULT: Eleven
      compounds were obtained from the 95% EtOH extract. The structures were determined
      as: annosquamosin C(1),15, 16-epoxy-17-hydroxy-ent-kau-ran-19-oic acid (2),16,17
      dihydroxy-ent-kau-ran-19-oic acid(3), annosquamosin A(4), ent-kaur-16-en-19-oic
      acid (5), 19-nor-ent-kauran4-ol-17-oic acid (6),16-hydroxy ent-kau ran-19-oic
      acid (7), ent-15beta-hydroxy-kaur-16-en-19-oic acid (8), annosquamosin B (9), ent
      16beta, 17-dihydroxykauran-19-al (10), 16, 17-dihydroxy-ent-kauran-19-oic acid me
      thyl ester (11). Compounds 1,2,3,5,9 showed different inhibitory activities
      against 95-D lung cancer cells,the effect of compound 5 was strongest with the
      IC50 value 7.78 micromol x L(-1); Compounds 2, 5, 9 showed inhibitory activities
      against A2780 ovarian cancer cells, the effects of compounds 2 and 9 were strong
      with the IC50 values being 0.89, 3.10 micromol x L(-1), respectively. CONCLUSION:
      Compound 2 was firstly isolated from this family, while compound 8 and 10 were
      first found from this genus and the title species, respectively. The in vitro
      anti-tumor test showed compound 5 significantly inhibited 95-D lung cancer cells
      and compounds 2 and 9 exhibited remarkbale activity against A2780 ovarian cancer
      cells.

PMID- 23126193
TI  - [Chemical constituents and antibacterial activity contained in Caesalpinia
      millettii].
AB  - To study chemical constituents contained in roots of Caesalpinia millettii by
      HPLC. Six homoisoflavonoids were identified by spectroscopic data and
      physicochemical property as eucomin (1), intricatinol (2), 8-methoxybonducellin
      (3), bonducellin (4), 8-methoxyisobonducellin (5) and 3-(4-methoxybenzyl) -5, 7
      dimethoxychroman-4-one (6). All compounds were separated from the root of this
      genus for the first time. An antibacterial screening was made on eight monomeric
      compounds. Among them, 8-methoxyisobonducellin, intricatinol, bergenin,
      hyperoside and 11-O-galloylbergenin showed a inhibitory effect on Staphylococcus
      aureus, Klebsiella Peneumoniae, Beta streptococcus and Aeruginosus bacillus.

PMID- 23126194
TI  - [Water-soluble non-alkaloid chemical constituents contained in Corydalis yanhusuo
      by trimethylsilyl derivatization GC-MS].
AB  - OBJECTIVE: To study the water-soluble non-alkaloid chemical constituents of
      Corydalis yanhusuo. METHOD: The 80% alcohol extracts of C. yanhusuo passed
      through DA201 macroporous resin. Eluted fractions were collected and passed
      though 732 # cation exchange resin. Water eluate was collected, dried and derived
      with trimethylsilane. Gas Chromatography/Mass Spectrometry and NIST 2005 library
      were adopted for MS/MS mass spectrogram to infer the compound structure. RESULT:
      Sixteen compounds were tentatively identified from about fifty peaks detected by
      GC-MS and identified as hydroxyl and carboxyl polar compounds. CONCLUSION: These
      sixteen compounds were found for the first time in C. yanhusuo. The results
      provide scientific basis for in-depth development of C. yanhusuo.

PMID- 23126195
TI  - [Quantitative model for patchouli alcohol in Pogostemon cablin by near-infrared
      spectroscopy].
AB  - OBJECTIVE: To establish a near-infrared spectroscopy quantitative model for rapid
      determination of the patchouli alcohol content in Pogostemon cablin. METHOD: The
      gas chromatography was adopted for determining the content of patchouli alcohol
      content in 102 batches of P. cablin samples. Their near-infrared spectrograms
      were collected and preprocessed by standard normal variate and the first
      derivative of Savitsky-Golay. The quantitative model of patchouli alcohol content
      was established by the partial least squares regression analysis. RESULT:
      According to the correction model established in this study, the root-mean-square
      error of calibration, the root-mean-square error of prediction and the root-mean
      square error of cross-validation of the calibration model for Patchouli alcohol
      were 0.991 10, 0.012 9, 0.012 8 and 0.033 15, respectively. CONCLUSION: The near
      infrared spectroscopy quantitative model established in this study is stable,
      accurate and reliable for the rapid determination of the content of patchouli
      alcohol in P. cablin.

PMID- 23126196
TI  - [Effect of icariin on learning and memory abilities and activity of cholinergic
      system of senescence-accelerated mice SAMP10].
AB  - OBJECTIVE: To investigate the effect of icariin (ICA) on learning and memory
      abilities and cholinergic system in senescence-accelerated mice SAMP10. METHOD:
      The 8-month-old senescence-accelerated mice were randomly divided into the model
      SAMP10 group and the positive Donepezil group (1 mg x kg(-1)) and ICA groups (50,
      100, 200 mg x kg(-1)), with 12 mice in each group. Another 12 8-month-old mice
      SAMR1 were selected as the normal control group. After 30 days of oral
      administration, Morris water maze, SMG-2 water maze and experimental platform
      were used to test the effects of ICA on learning and memory abilities of SAMP10
      groups. By colorimetric determination of AChE activity in the cortex, enzyme
      linked immunosorbent assay detection of ACh, ChAT, MCBC of the cerebral cortex,
      the effect of ICA on the cholinergic system of SAMP10 was observed. RESULT: ICA
      could improve the abilities of space exploration and positioning navigation of
      SAMP10, shorten the latency in SMG-2 water maze, enhance their jumping ability in
      response to the passive test, and increase levels of ACh, ChAT, MCBC in the
      cerebral cortex of SAMP10. But its active effect on AChE in SAMP10 cortex was not
      obvious. CONCLUSION: Different doses of icariin can improve learning and memory
      abilities of SAMP10 to varying degrees, which may be related to its effect on the
      cholinergic system.

PMID- 23126197
TI  - [Study on effect and mechanism of salidroside on cognitive ability of Abeta1-40 
      induced Alzheimer's disease model rats].
AB  - OBJECTIVE: To study the effect and possible impact mechanism of salidroside on
      cognitive ability of Alzheimer's disease (AD) model rats induced by amyloid beta
      peptide (Abeta1-40). METHOD: Abeta1-40 was injected into bilateral hippocampus to
      create the AD model. Afterwards, different doses of salidroside (25, 50, 75 mg x
      kg(-1)) were orally administered for 21 days. Rats' learning and memory abilities
      were detected by Morris water maze testing system. The levels of the superoxide
      dismutase (SOD), malondialdehyde (MDA), and the expression of nuclear factor
      kappaB (NF-kappaB), inducible nitric oxide synthase (iNOS) and receptor for
      advanced glycation end products (RAGE) protein in hippocampus were also detected
      by different methods. RESULT: The place navigation test showed longer escape
      latency, low frequency of platform quadrant crossing per unit time, damage in
      learning capacity, significant decrease in SOD acivity in hippocampus, notable
      increase in MDA content, NF-kappaB, iNOS and RAGE protein expressions in rats.
      Salidroside (50, 75 mg x kg(-1)) significantly alleviated the impairments of
      learning and memory ability. The activity of SOD increased in salidroside (50
      droside group compared with that of the Alzheimer's disease group (P < 0.01).
      CONCLUSION: Salidroside may treat Alzheimer's disease by inhibiting the oxidative
      stress.

PMID- 23126198
TI  - [Effect of Panax notoginseng saponins on expression of alpha-secretase mRNA in
      brains of senescence-accelerated SAMP8 mice].
AB  - OBJECTIVE: To study the effect of Panax notoginseng saponins (PNS) on expression
      of alpha-aecretase mRNA in the brains of senescence-accelerated SAMP8 mice.
      METHOD: SAMP8 mice were randomly divided into the control group, the PNS high
      dosage group (200 mg x kg(-1)), the PNS low-dosage group (100 mg x kg(-1)) and
      the huperzine A group (0.3 mg x kg(-1)), with eight mice in each group. The
      control group and each administration group were orally administered with the
      same volume of double distilled water once for consecutively two months. The
      expression of alpha-secretase (ADAM 9, ADAM10, ADAM17) mRNA was assayed by real
      time fluorescence quantitative polymerase chain reaction (Real-time PCR). RESULT:
      The expression of ADAM9 mRNA in PNS high-dosage group and huperzine A group were
      significantly higher than that of the control group (P < 0.05). The expression of
      ADAM10 in the PNS high-dosage group, the PNS low-dosage group and the huperzine A
      group showed no significant difference from the control group. CONCLUSION: PNS
      can up-regulate expressions of ADAM9 mRNA and down-regulate expressions of ADAM10
      mRNA in the brains of SAMP8 mice.

PMID- 23126199
TI  - [Regulating effect of Ginkgo biloba extract 50 on hippocampal inflammation
      related cytokines in senile rats].
AB  - OBJECTIVE: To investigate the regulating effect of Ginkgo biloba extract 50
      (GBE50) on pre-inflammatory factors interleukin-1 beta (IL-1beta), tumor necrosis
      factor-alpha (TNF-alpha) and anti-inflammatory factors interleukin-4 (IL-4),
      interleukin-10 (IL-10) of hippocampus in senile rats, in order to explore the
      protective mechanism of GBE50 on central nervous system of senile animals.
      METHOD: SD rats were randomly divided into four groups: the normal group, the
      model group, the GBE50 group and the EGB761 group. Rats were intraperitoneally
      injected with 100 mg x kg(-1) D-galactose every day for 42 days to establish the
      senile rat model. At the 21st day, the GBE50 group and the EGB761 group were
      orally administered with 60 mg x kg(-1) for 21 days. IL-1beta mRNA and TNF-alpha
      mRNA expressions were detected by real-time fluorescence quantitative PCR assay,
      IL-1beta and TNF-alpha protein expressions were detected by immunohistochemistry,
      IL-4 and IL-10 protein contents were detected by ELISA. RESULT: D-galactose
      caused imbalance between pre-inflammatory factors and anti-inflammatory factors
      of hippocampus in senile rats, GBE50 and EGB761 reduced IL-1beta mRNA expression
      (P < 0.05) and TNF-alpha and IL-1beta protein level (P < 0.01) and up-regulated
      IL-10 protein content (P < 0.01, P < 0.05). CONCLUSION: The mechanism of GBE50 in
      protecting central nervous system is probably related to its effect in mitigating
      inflammatory of central nervous system.

PMID- 23126200
TI  - [Effect and mechanism of gastrodin in relaxing isolated thoracic aorta rings in
      rats].
AB  - OBJECTIVE: To investigate the effect of gastrodin in relaxing isolated thoracic
      aorta rings in rats and discuss its possible mechanism. METHOD: Isotonic tension
      of isolated thoracic aortic rings in rats with norepineprine (NE) and KCl was
      recorded to observe the vasodilatory effect of gastrodin and the influence of
      various drugs on it. RESULT: Gastrodin had the effect in relaxing thoracic aortas
      with or without endothelium, and there was no significant difference. NG-nitro-L
      argininemethylester (L-NAME, 1 x 10(-4) mol x L(-1)), methylene blue (MB, 1 x 10(
      5) mol x L(-1)), indomethacin (INDO, 1 x 10(-5) mol x L(-1)) had no effect on the
      vasodilation action of gastrodin on thoracic aortas precontracted by NE. 4
      aminopyrimide (4-AP, 1 x 10(-4) mol x L(-1)), tetrathylamonium (TEA, 1 x 10(-3)
      mol x L(-1)), BaCl2 (1 x 10(-4) mol x L(-1)) and glibenclamide (Gli, 1 x 10(-5)
      mol x L(-1)) could inhibit gastrodin's effect in relaxing thoracic aorta rings.
      In the absence of Ca2+, pre-incubated gastrodin showed a notable inhibitory
      effect in relaxing NE contraction. CONCLUSION: Gastrodin shows a dose-dependent
      and endothelium-independent effect in relaxing rat isolated thoracic aorta rings.
      The mechanism is related to K+ channel, inhibition of release of Ca+ stored in
      endoplasmic reticulum of vascular smooth muscle cells and inflow of external
      calcium Ca2+.

PMID- 23126201
TI  - [Study on toxicity of uniform design-based compatible use of Veratrum nigrum and
      asarum].
AB  - The compatible use of Veratrum nigrum with asarum, is one of the eighteen
      incompatible pairs. To research the toxic regularity of the compatible use of V.
      nigrum and asarum, this experiment adopted the uniform design combining with
      acute toxicity test, with the number of died animals as the observation
      indicator. The results showed that the toxicity came from the common effect of V.
      nigrum and asarum, and V. nigrum after the compatible use, and V. nigrum made a
      greater contribution to the toxicity caused by the compatible use. But the
      toxicity did not absolutely enhance with the increase in use of V. nigrum.

PMID- 23126202
TI  - [Study on protective effect and mechanism of fufang tangshang gao on deep grade
      II skin burn in rats].
AB  - OBJECTIVE: To observe the protective effect and mechanism of Fufang Tangshang Gao
      (FFTSG) on deep grade II burn wounds in rats. METHOD: The deep grade II skin burn
      model was established. FFTSG was adopted for wounds once everyday for 21 d.
      Samples were collected at different time points after burn to determine the wound
      healing rate, the wound tissues water content, VEGF, TNF-alpha and IL-1. RESULT:
      At different time points, FFTSG (0.4, 0.2, 0.1 g x g(-1)) could increase the
      wound healing rate and VEGF content and decrease the tissues water content, TNF
      alpha and IL-1. CONCLUSION: FFTSG shows a notable protective effect on deep grade
      II burn wounds in rats by obviously promoting the wound healing and decreasing
      the wound tissues water content. Its mechanisms may be related with the increase
      in VEGF synthesis and release of wound tissues and the decrease in TNF-alpha and
      IL-1 in rat blood serum.

PMID- 23126203
TI  - [Preliminary study of effects of andrographolide on Staphylococcus epidermidis
      biofilms].
AB  - OBJECTIVE: To provide a new therapeutic approach for Staphylococcus epidermidis
      biofilm-associated infections by the study of inhibitory effect of
      andrographolide (AG) on S. epidermidis biofilm. METHOD: S. epidermidis biofilms
      were set up in vitro, erythromycin was acted as the positive control agent, XTT
      reduction assay was used to evaluate AG on the initial adhesion of S. epidermidis
      and bacterial metabolism within biofilm, microscope was applied to observe
      biofilm morphology, and Congo red assay was used to detect polysacchatide interc
      ellular adhesion (PIA)formation when exposed to AG. RESULT: AG showed inhibitory
      effects against the initial adhesion of S. epidermidis at concentrations of 1
      000,100, 10 mg x L(-1), respectively,and inhibited metabolism of biofilm bacteria
      at the concentration of 31.25 mg x L(-1), and exhibited significantly inhibition
      against the biofilm morphology at the concentration of 250 mg x L(-1), while did
      not display inhibition against PIA formation at the concentration of 10 mg x L(
      1). CONCLUSION: AG could remarkably inhibit biofilm formation of S. epidermidis,
      although it was less potent than erythromycin.

PMID- 23126204
TI  - [Identification of two small molecule inhibitors of hypoxia-inducible factor 1
      with different cell-based screening model].
AB  - OBJECTIVE: To investigate the inhibitory activity of HIF-1 by triptolide and
      manasaantin A, two cell-based models with luciferase report gene assay were
      established. METHOD: Two cell-based models of HIF-1 were used to evaluate HIF-1
      inhibition activity of triptolide and manasaantin A. Secreted VEGF expression
      induced by hypoxia was detected by ELISA with two compounds. The growth
      inhibition of different solid tumor cell lines was measured by the MTT assay.
      RESULT: The expression of firefly luciferase was induced by hypoxia in U251-HRE
      and T47D-HRE cells. U251-HRE model was suitable for the detection of HIF-1
      inhibition activity of triptolide. The IC50 of triptolide on HIF-1 activity was
      (3.4 +/- 0.5) x 10(-8) mol x L(-1). The report gene assay using T47D cells co
      transfected with pGL2-TK-HRE and pRL-CMV showed more sensitive inhibition
      activity of HIF-1 on manassantin A than that of detected by U251-HRE model. The
      IC50 of manassantin A on HIF-1 activity was (2.4 +/- 0.6) x 10(-8) mol x L(-1).
      HIF-1 target gene VEGF was also inhibited by test compounds on protein level in
      T47D cells. Manasaantin A showed selective inhibition on the growth of human
      solid cancer cell lines, especially on breast cancer and pancreatic cancer cells.
      Meanwhile, triplotide showed strong proliferation inhibition activity on all
      tested cell lines. CONCLUSION: It is very important to select a suitable cell
      based report gene assay of HIF-1 for screening of different kinds of inhibitor.

PMID- 23126205
TI  - [Mechanisms of Wuling mycelia powder on memory retrieval impairment in rats with
      chronic epilepsy].
AB  - OBJECTIVE: To investigate the mechanisms of Wuling mycelia powder on memory
      retrieval impairment in rats with chronic epilepsy. METHOD: SD rats were randomly
      divided into four groups: the pentylenetetrazole-kindling group (the model
      control group), the low dose of Wuling mycelia powder (0.3 g x kg(-1), ig) group,
      the high dose of Wuling mycelia powder (0.6 g x kg(-1), ig) group and the blank
      control group. After being successfully trained in the 8-arm (4-arm baited)
      radial maze, the rats were intraperitoneally injected with a subconvulsive dose
      (35 mg x kg(-1)) of pentylenetetrazole (saline in control group) every 48 h for
      12 times. Wuling mycelia powder were orally administered 30 min before every
      pentylenetetrazole injection. Memory retrieval was tested at the same maze.
      Phosphorylated CREB were analyzed by Western blot. Brain pathological sections
      were stained using HE, hippocampal nerve cells were observed under optical
      microscopes. RESULT: Both of reference and working memory abilities of these
      chronic epilepsy rats were impaired as expressed in the 8-arm radial maze but
      reversed by Wuling mycelia powder to some extent. Chronic epilepsy caused a
      decreasing p-CREB in hippocampal nerve cells and injury in hippocampal CA1 region
      and CA3 region among rats. Wuling mycelia powder inhibited hippocampal p-CREB
      from decreasing and protected hippocampal nerve cells. CONCLUSION: Wuling mycelia
      powder could ameliorate memory impairment induced by epilepsia. Its mechanism may
      be related to the increase in p-CREB expression in brain and the protective
      effect on hippocampal nerve cells.

PMID- 23126206
TI  - [Comparison on in vivo pharmacokinetics of brucine, total alkaloids of Strychni
      Semen and Strychni Semen pulveratum in rats].
AB  - OBJECTIVE: To study different in vivo pharmacokinetic regularity of brucine,
      total alkaloids of scorched sand-prepared Strychni Semen products and Strychni
      Semen pulveratum in rats, and probe into mutual impact between single component
      and compound. METHOD: Rats in each group were orally administered with brucine,
      total alkaloids of scorched sand-prepared Strychni Semen products and Strychni
      Semen pulveratum suspension. The in vivo plasma concentrations of brucine in rats
      were determined by HPLC. A compartment model was made for the blood drug
      concentration-time curve using 3P97 software package and the pharmacokinetic
      parameters of each group were calculated and compared. RESULT: The in vivo
      metabolic process of brucine in rats complied with the two-compartment model,
      weight W = 1/C2. The results of variance analysis showed that among three
      existing forms of brucine with same dosage, the brucine solution group and the
      total alkaloids group of scorched sand-prepared Strychni Semen products showed
      significant differences in C(max), MRT (P < 0.05); and the brucine solution group
      and the Strychni Semen pulveratum suspension group showed significant differences
      in C(max), AUC(0-t), and AUC(0-infinity), in which the latter displayed minimum
      C(max), AUC(0-t) and AUC(0-infinity). CONCLUSION: The total alkaloids group of
      scorched sand-prepared Strychni Semen products showed a relatively longer
      retention time of effective components of brucine in plasma, while the Strychni
      Semen pulveratum suspension group showed a lower bioavailability.

PMID- 23126207
TI  - [In vitro effect of Banxiaxiexin Tang and different conbinations on hepatic
      CYP450 in rats].
AB  - To study the effect of Banxiaxiexin Tang and different conbinations on CYP450 in
      rat liver microsomes, from the point of liver metabolism, evaluate significance
      of Banxiaxiexin Tang compatibility. The rats were randomly divided into five
      groups: Banxiaxiexin Tang group, pungent-swelling group, bitter-descending group,
      sweet-invigorating group and control group, which were all given decoction by
      gavage. Using liver microsomes in vitro incubation method, probe substrate were
      incubated and their metabolites was detected by ultra-high performance liquid
      chromatography, then was calculated metabolic rate to reflect the drug-treated
      liver microsomes CYP2C6, CYP2E1, CYP3A1/2 activity. The results showed that
      comparing with the control group, both Banxiaxiexin Tang group and bitter
      descending group showed inhibition on all enzyme subtype (P < 0.01), pungent
      swelling group showed significant inhibition on CYP2C6, but no inhibition on
      CYP2E1 and CYP3A1/2; sweet-invigorating group showed inhibition on CYP2C6 and
      CYP2E1, but no inhibition on CYP3A1/2. Compared the inhibition on CYP with the
      three conbinations, bitter-descending group was significant higher than other
      groups. Banxiaxiexin Tang group showed inhibition on rat liver microsomes CYP450,
      and the activity maybe come from bitter-descending group.

PMID- 23126208
TI  - [Determination of plasma protein binding rate of vitexin].
AB  - OBJECTIVE: To establish an analytical method on vitexin concentration in plasma
      to determine the plasma protein binding rate of vitexin. METHOD: The equilibrium
      dialysis method and HPLC were adopted to determine vitexin concentration in
      plasma, calculate human plasma protein binding rate of vitexin and compare rat
      and human plasma protein binding rates of vitexin. RESULT: At 2-16 mg x L(-1),
      there was no significant difference in the plasma protein binding rate. But the
      human plasma protein binding rate of vitexin was higher than its rat plasma
      protein binding rate, indicating a significant difference in rat and human plasma
      protein binding rates of vitexin. CONCLUSION: Vitexin has a higher protein
      binding rate with both rat plasma and human plasma.

PMID- 23126210
TI  - [Establishing quality assurance system of processed Chinese medicine to ensure
      clinical effect of traditional Chinese medicine].
AB  - For the purpose of stabilizing and enhancing the clinical effect, the author
      suggested that it should develop the key technology of integrated innovation
      research such as origin producing area processing technology, medicinal parts and
      energy-saving rapid drying technology, process control technology, quality
      evaluation key technology, packaging and bar code identification technology to
      establish the quality assurance system of processed Chinese medicine, which is
      the key to ensure the clinical effect of traditional Chinese medicine.

PMID- 23126211
TI  - [Thought and application of traditional Chinese medicine multiple drug delivery
      system based on material basis component].
AB  - To aim directly at the research status of Chinese drugs pharmaceutics, this study
      provides a new research idea "traditional Chinese medicine multiple drug delivery
      system based on material basis component". This thought according to whole
      concept, syndrome, and Chinese medicine characteristics of multi-component, multi
      target, multi-effect. The premise of designing traditional Chinese medicine
      multiple drug delivery system is material basis component, and the purpose is to
      improve bioavailability. The example of multi-drug delivery system of tongmai
      micro-pellets is expounded for application. This new research model of Chinese
      drugs pharmaceutics provides new strategies and methods for the development of
      modern Chinese drug delivery systems.

PMID- 23126209
TI  - [Advance of pharmacological studies on Valeriana jatamansi].
AB  - As a traditional Chinese medicine, Valeriana jatamansi has a long history of
      application in China. It is widely distributed and commonly adopted by many
      ethnic groups. In particular, its roots have a wide range of medicinal value.
      With the increasingly more attention on it from domestic and foreign researchers,
      there have been more and more studies on its pharmacological activity and
      mechanism. This essay summarizes domestic and foreign reports on its
      pharmacological activity and mechanism.

PMID- 23126212
TI  - [Development and application of Dai ethnic medicine "Jajie"].
AB  - "Jajie" means antidote in Dai language. As an important part of theories of Dia
      ethnic medicine, "Jajie" focuses on antidote before treatment. With wide
      application and exact effect, "Jajie" plays an important role in preventing and
      treating diseases, especially liver disease, digestive system diseases, metabolic
      diseases, skin diseases and so on. Therefore, systematic collection, analysis and
      studies on Dai ethnic medicine "Jajie" is an important content in the development
      of the theory of Dai ethnic medicine as well as new drugs. This essay briefs the
      general situation of "Jajie" and the advance of its studies, and gives comments
      on Jajie's development.

PMID- 23126213
TI  - [Burning sensation in oral cavity--burning mouth syndrome in everyday medical
      practice].
AB  - Burning mouth syndrome (BMS) refers to chronic orofacial pain, unaccompanied by
      mucosal lesions or other evident clinical signs. It is observed principally in
      middle-aged patients and postmenopausal women. BMS is characterized by an intense
      burning or stinging sensation, typically on the tongue or in other areas of the
      oral mucosa. It can be accompanied by other sensory disorders such as dry mouth
      or taste alterations. Probably of multifactorial origin, and often idiopathic,
      with a still unknown etiopathogenesis in which local, systemic and psychological
      factors are implicated. Currently there is no consensus on the diagnosis and
      classification of BMS. This study reviews the literature on this syndrome, with
      special reference to the etiological factors that may be involved and the
      clinical aspects they present. The diagnostic criteria that should be followed
      and the therapeutic management are discussed with reference to the most recent
      studies.

PMID- 23126214
TI  - Administration of preemptive analgesia by diclofenac to prevent acute
      postcraniotomy headache.
AB  - PURPOSE: Postcraniotomy headache (PCH) is a frequent perioperative complication
      in neuroanesthesia. The aim of the present work was to assess the incidence of
      PCH and to test the efficacy and safety of preoperatively administered
      diclofenac. METHODS: Patients undergoing craniotomies for intracranial tumor
      resections were enrolled. In the case group 100 mg diclofenac p.o. one hour prior
      to surgery was used as a preemptive analgesic along with infiltration of the
      surgical site with a combination of lidocaine and epinephrine. In controls only
      surgical site infiltration was used. VAS scores were assessed preoperatively, on
      the day of surgery (DoS), on the 1st and 5th postoperative days. RESULTS: We have
      found that PCH of any severity is between 50-90% during the first five days after
      surgery. The number of cases characterized as "no pain" significantly decreased
      in the early postoperative period, but remained in both groups still higher on
      the 5th postoperative day than observed preoperatively. In both groups, the
      number of headaches characterized as mild pain remained relatively stable and
      substantial increases in case numbers were observed in moderate and severe
      headaches, showing a declining tendency over time in the postoperative period. A
      significant effect of diclofenac pretreatment was observed compared to controls
      on DoS (chi2: 10.429, p<0.015), on the 1st (chi2: 8.75, p<0.032) and 5th
      postoperative days (chi2: 14.3, p<0.002). CONCLUSIONS: The relatively low
      incidence of severe PCH on day five in the diclofenac group may indicate that
      preoperatively administered diclofenac effectively reduces postcraniotomy
      headache. A randomized study is encouraged to test this hypothesis.

PMID- 23126216
TI  - [Prospective study of the clinical features of cluster headache].

PMID- 23126215
TI  - [Prospective study of the clinical features of cluster headache].
AB  - INTRODUCTION: Although cluster headache (CH) is one of the most severe human pain
      syndromes, its symptoms and therapeutic possibilities may be suboptimally
      recognised in current medical practice in Hungary. AIM: To present the clinical
      characteristics of CH based on a prospective study of patients attending the
      Headache Service of the Department of Neurology, Semmelweis University. METHODS:
      We collected information about the symptoms, diagnosis and previous treatment of
      CH patients by filling in a 108-item questionnaire during outpatient visits.
      RESULTS: In the 5-year period between 2004 and 2008 we obtained data from 78 CH
      patients (57 males and 21 females; mean age: 44.6 +/- 14.6 years). The
      male:female ratio did not change in subgroups based on disease onset (calendar
      years). Ninety-three percent considered CH the most severe pain state of their
      life. The pain was strictly unilateral, affecting the territory of the 1st
      trigeminal division in all patients. The attacks were accompanied by signs of
      ipsilateral cranial parasympathetic activation (lactimation 83%, conjunctival
      injection 67%, rhinorrhea 56%, nasal congestion 43%); less frequently, signs of
      sympathetic dysfunction (ptosis 48%, miosis 7%) were also present. Two patients
      had attacks showing the typical localisation, severity and time course of CH
      attacks, but not accompanied by autonomic phenomena. A considerable part of the
      patients also observed symptoms that are usually ascribed to migraine (nausea
      41%, vomiting 18%, photophobia 68%, phonophobia 58%). This may have been
      instrumental in the fact that, regardless of the characteristic clinical
      symptoms, the diagnosis of CH took 10 years on average. At the time of their
      examination 63% of patients were not using adequate abortive medications and 59%
      did not have an adequate prophylactic measure. DISCUSSION: Cluster headache is
      characterised by attacks of devastating pain that warrant an early diagnosis and
      adequate treatment. Our study underlines that information about the diagnosis and
      therapy of CH should be emphasized on occasions of neurology specialty training
      and continuing medical education.

PMID- 23126217
TI  - Health status and costs of ambulatory patients with multiple sclerosis in
      Hungary.
AB  - BACKGROUND AND PURPOSE: Data on disease burden of multiple sclerosis from Eastern
      Central Europe are very limited. Our aim was to explore the quality of life,
      resource utilisation and costs of ambulating patients with multiple sclerosis in
      Hungary. METHODS: Cross-sectional questionnaire survey was performed in two
      outpatient neurology centres in 2009. Clinical history, health care utilisation
      in the past 12 months were surveyed, the Expanded Disability Status Scale and the
      EQ-5D questionnaires were applied. Cost calculation was conducted from the
      societal perspective. RESULTS: Sixty-eight patients (female 70.6%) aged 38.0 (SD
      9.1) with disease duration of 7.8 (SD 6.7) years were involved. Fifty-five
      (80.9%) had relapsing-remitting form and 52 (76.5%) were taking immunomodulatory
      drug. The average scores were: Expanded Disability Status Scale 1.9 (SD 1.7), EQ
      5D 0.67 (SD 0.28). Mean total cost amounted to 10 902 Euros/patient/year (direct
      medical 67%, direct nonmedical 13%, indirect costs 20%). Drugs, disability
      pension and informal care were the highest cost items. Costs of mild (Expanded
      Disability Status Scale 0-3.5) and moderate (Expanded Disability Status Scale 4.0
      6.5) disease were 9 218 and 17 634 Euros/patient/year respectively (p<0.01), that
      is lower than results from Western European countries. CONCLUSION: Our study
      provides current inputs for policy making and contributes to understanding
      variation of cost-of-illness of multiple sclerosis in Europe.

PMID- 23126218
TI  - [Brain tissue water content determination based on T1 relaxation time of water
      and quantitative cerebral 1H MRS at 3T using water as an internal reference].
AB  - OBJECTIVE: Application of a quantitative MR-spectroscopic method for 3T clinical
      scanners based on tissue water content as an internal reference. PATIENTS AND
      METHODS: Six (22 +/- 2 yrs) volunteers were involved in the study. We performed
      T1 relaxation time measurements in a particular slice of the brain at 1T and 3T.
      Based on the validated water content measurement at 1T, the correlation of
      relaxation time T1 and water content was determined at 3T. The resulting water
      content served as internal reference for the quantification of localizated MR
      spectroscopic measurement. RESULTS: At 3T our method resulted in 37.6 +/- 0.5
      mol/l and 46.4 +/- 1.5 mol/l tissue water content in the white and gray matter,
      respectively. Calibration based on water content led to following metabolite
      concentrations: N-acetyl-aspartate 7.79 +/- 0.67 mmol/l; creatine 3.76 +/- 0.28
      mmol/l; choline 3.68 +/- 0.47 mmol/l; myo-inositol 10.35 +/- 3.70 mmol/l in the
      white matter; and N-acetyl-aspartate 8.20 +/- 0.45 mmol/l; creatine 4.76 +/- 0.18
      mmol/l; choline 2.64 +/- 0.35 mmol/l; myo-inositol 8.32 +/- 1.42 mmol/l in the
      grey matter. CONCLUSIONS: Tissue water content based on T value at 3T shows good
      accordance with gravimetric or other MR methods in the literature. Using it as an
      internal reference resulted in white matter metabolite concentrations that are in
      the range of previously published data. Comparing metabolite values of grey
      matter is more difficult because data in the literature substantially differ. The
      presented method is simple and easily applicable on any MR scanner without
      complicated correction and calibration steps.

PMID- 23126219
TI  - [Role of the intraoperative electrical brain stimulation in conserving the speech
      and language function in neurosurgical procedures on conscious patients].
AB  - AIM OF THE STUDY: To summarize the results gained with awake craniotomies, which
      were performed in either low grade glioma patients or epilepsy surgical patients
      whose tumor or epileptogenic zone, was in the vicinity of eloquent, mostly
      language, cortices. PATIENT SELECTION AND METHODS: In our retrospective study we
      selected 16 patients who were operated awake between 1999-2011 at the
      Neurosurgical Department of MAV Korhaz Budapest, or at the National Institute of
      Neurosciences in Budapest, or at the Neurosurgical Department of the University
      of Debrecen in Debrecen. In the presurgical evaluation if it was possible we
      performed functional magnetic resonance imaging, tractography and detailed
      neuropsychological testing. At the National Institute of Neurosciences all
      patients were operated with the aid of MR guided neuronavigation. RESULTS:
      Anesthesia was carried out without complications in all of the 16 cases.
      Monitoring of sleep deepness has significantly contributed to the safety of
      anesthesia during the superficial anesthezied states of the operation. The
      intraoperative neuropsychological tasks used for testing language were sensitive
      enough to judge the little disturbances in speech during stimulation. Stimulation
      evoked seizures could be adequately managed during surgery and did not influence
      the outcome of the procedures. The use of neuronavigation helped significantly by
      planning the optimal place for the craniotomy and by intraoperative orientation.
      CONCLUSIONS: Awake craniotomies require well practiced surgical teams, which
      requires the cooperation of neuro-anesthesiologits, neurosurgeons,
      neuropsychologist and electrophysiologists. It has two goals, first to reduce the
      time of surgery to minimize surgical complications, secondly the detailed
      intraoperative mapping of cognitive and motor functions to avoid any neurological
      deficit. The intraoperative anatomical data provided by the neuronavigation and
      the functional data provided by awake intraoperative stimulation of the patient
      together serve the safety of the patient which is essential in the neurologically
      minimal invasive neurosurgical approach of the 21st century.

PMID- 23126220
TI  - Multiple sclerosis coexisting with spinal cord ependymoma: a case report.
AB  - BACKGROUND: In this paper, we report a coexistence of multiple sclerosis and an
      intradural spinal cord tumor. CASE REPORT: A 34-year-old woman who had a history
      of relapsing-remitting multiple sclerosis for the last 15-years presented with
      acute sensory loss and spasticity in her left lower limb and her spinal magnetic
      resonance imaging study revealed an intradural spinal cord tumor in the lumbar
      spine, further diagnosed as ependymoma. CONCLUSION: We call attention to this
      rare association of MS and a spinal cord tumor, emphasizing the need for
      investigation of new symptoms during the evolution of MS.

PMID- 23126221
TI  - [Rivaroxaban versus warfarin: results of the ROCKET study].

PMID- 23126222
TI  - [Hungarian neurologists, Gyula Donath (1849-1944)].

PMID- 23126223
TI  - [Neurosciences and artificial intelligence].

PMID- 23126224
TI  - [Dear colleagues! Rehabilitative care in Hungary].

PMID- 23126225
TI  - Thermal ablation in renal cell carcinoma: what affects renal function?
AB  - Because of its minimally invasive nature, thermal ablation is increasingly
      performed in patients with renal cell carcinoma (RCC) who are poor surgical
      candidates. Thermal ablation has been associated with excellent outcomes, and
      thus has been regarded as a viable alternative to nephron-sparing surgery. Many
      papers report minimal to no reduction in renal function after ablation therapies.
      However, in order to achieve good local control, normal renal tissue must be
      sacrificed, subsequently leading to reduced renal function. The amount of normal
      renal tissue to be ablated depends on the size, location, and number of RCCs, as
      well as the type of thermal ablation applied. However, there are few reports
      about what reduces renal function following thermal ablation therapies. The
      purpose of this review was to discuss factors that affect reduction in renal
      function and to assess the relationship between local tumour control and renal
      function.

PMID- 23126227
TI  - NanoUPLC-MSE proteomic data assessment of soybean seeds using the Uniprot
      database.
AB  - BACKGROUND: Recombinant DNA technology has been extensively employed to generate
      a variety of products from genetically modified organisms (GMOs) over the last
      decade, and the development of technologies capable of analyzing these products
      is crucial to understanding gene expression patterns. Liquid chromatography
      coupled with mass spectrometry is a powerful tool for analyzing protein contents
      and possible expression modifications in GMOs. Specifically, the NanoUPLC-MSE
      technique provides rapid protein analyses of complex mixtures with supported
      steps for high sample throughput, identification and quantization using low
      sample quantities with outstanding repeatability. Here, we present an assessment
      of the peptide and protein identification and quantification of soybean seed
      EMBRAPA BR16 cultivar contents using NanoUPLC-MSE and provide a comparison to the
      theoretical tryptic digestion of soybean sequences from Uniprot database.
      RESULTS: The NanoUPLC-MSE peptide analysis resulted in 3,400 identified peptides,
      58% of which were identified to have no miscleavages. The experiment revealed
      that 13% of the peptides underwent in-source fragmentation, and 82% of the
      peptides were identified with a mass measurement accuracy of less than 5 ppm.
      More than 75% of the identified proteins have at least 10 matched peptides, 88%
      of the identified proteins have greater than 30% of coverage, and 87% of the
      identified proteins occur in all four replicates. 78% of the identified proteins
      correspond to all glycinin and beta-conglycinin chains.The theoretical Uniprot
      peptide database has 723,749 entries, and 548,336 peptides have molecular weights
      of greater than 500 Da. Seed proteins represent 0.86% of the protein database
      entries. At the peptide level, trypsin-digested seed proteins represent only 0.3%
      of the theoretical Uniprot peptide database. A total of 22% of all database
      peptides have a pI value of less than 5, and 25% of them have a pI value between
      5 and 8. Based on the detection range of typical NanoUPLC-MSE experiments, i.e.,
      500 to 5000 Da, 64 proteins will not be identified. CONCLUSIONS: NanoUPLC-MSE
      experiments provide good protein coverage within a peptide error of 5 ppm and a
      wide MW detection range from 500 to 5000 Da. A second digestion enzyme should be
      used depending on the tissue or proteins to be analyzed. In the case of seed
      tissue, trypsin protein digestion results offer good databank coverage. The
      Uniprot database has many duplicate entries that may result in false protein
      homolog associations when using NanoUPLC-MSE analysis. The proteomic profile of
      the EMBRAPA BR-16 seed lacks certain described proteins relative to the profiles
      of transgenic soybeans reported in other works.

PMID- 23126226
TI  - Human stem cell-derived astrocytes and their application to studying Nrf2
      mediated neuroprotective pathways and therapeutics in neurodegeneration.
AB  - Glia, including astrocytes, are increasingly at the forefront of
      neurodegenerative research for their role in the modulation of neuronal function
      and survival. Improved understanding of underlying disease mechanisms, including
      the role of the cellular environment in neurodegeneration, is central to
      therapeutic development for these currently untreatable diseases. In these
      endeavours, experimental models that more closely reproduce the human condition
      have the potential to facilitate the transition between experimental studies in
      model organisms and patient trials. In this review we discuss the growing role of
      astrocytes in neurodegenerative diseases, and how astrocytes generated from human
      pluripotent stem cells represent a useful tool for analyzing astrocytic
      signalling and influence on neuronal function.

PMID- 23126229
TI  - Karyotype evolution and phylogenetic analyses in the genus Cardiospermum L.
      (Paullinieae, Sapindaceae).
AB  - Cardiospermum L. belongs to the Paullinieae tribe (Sapindaceae) and comprises 16
      species. Of these, 12 species are present in South America and all occur in
      Brazil. Cardiospermum shows the most variable chromosome number of the tribe.
      Phylogenetic relationships within the genus Cardiospermum, especially with other
      species of the tribe, are poorly understood. This research focuses on
      characterisation of the karyotypic features of Cardiospermum using conventional
      cytogenetic methods, CMA/DAPI chromosome banding and fluorescence in situ
      hybridisation (FISH). To elucidate the phylogeny of the genus, the nuclear
      markers ITS1 and ITS2 were sequenced and analysed using maximum parsimony and
      Bayesian inference. Cardiospermum shows important diversity in basic numbers,
      with x = 7, 9, 10, 11 and 12. All species studied have metacentric and
      submetacentric chromosomes, some species have subtelocentric chromosomes, while
      telocentric chromosomes are absent. The interphase nuclei differentiate the
      Cardiospermum species into two groups. The CMA(3) /DAPI chromosome banding
      revealed the presence of an AT-rich terminal region in C. corindum, C.
      grandiflorum and C. urvilleoides, whereas GC-rich regions were found in C.
      grandiflorum, C. halicacabum var. halicacabum, C. halicacabum var. microcarpum,
      C. heringeri and C. integerrimum. FISH revealed syntenic and non-syntenic
      distribution of the 18-5.8-26S and 5S rDNA. The syntenic distribution always
      occurred in the short arms of the same chromosome in all of the species. The
      phylogenetic relationships reveal, in part, the taxonomic arrangement of the
      genus Cardiospermum.

PMID- 23126228
TI  - Novel polypyrrole-coated polylactide scaffolds enhance adipose stem cell
      proliferation and early osteogenic differentiation.
AB  - An electrically conductive polypyrrole (PPy) doped with a bioactive agent is an
      emerging functional biomaterial for tissue engineering. We therefore used
      chondroitin sulfate (CS)-doped PPy coating to modify initially electrically
      insulating polylactide resulting in novel osteogenic scaffolds. In situ chemical
      oxidative polymerization was used to obtain electrically conductive PPy coating
      on poly-96L/4D-lactide (PLA) nonwoven scaffolds. The coated scaffolds were
      characterized and their electrical conductivity was evaluated in hydrolysis. The
      ability of the coated and conductive scaffolds to enhance proliferation and
      osteogenic differentiation of human adipose stem cells (hASCs) under electrical
      stimulation (ES) in three-dimensional (3D) geometry was compared to the noncoated
      PLA scaffolds. Electrical conductivity of PPy-coated PLA scaffolds (PLA-PPy) was
      evident at the beginning of hydrolysis, but decreased during the first week of
      incubation due to de-doping. PLA-PPy scaffolds enhanced hASC proliferation
      significantly compared to the plain PLA scaffolds at 7 and 14 days. Furthermore,
      the alkaline phosphatase (ALP) activity of the hASCs was generally higher in PLA
      PPy seeded scaffolds, but due to patient variation, no statistical significance
      could be determined. ES did not have a significant effect on hASCs. This study
      highlights the potential of novel PPy-coated PLA scaffolds in bone tissue
      engineering.

PMID- 23126231
TI  - IWH: an Initiative for Women's Health with a better quality of life.

PMID- 23126230
TI  - Detection of Burkholderia pseudomallei O-antigen serotypes in near-neighbor
      species.
AB  - BACKGROUND: Burkholderia pseudomallei is the etiological agent of melioidosis and
      a CDC category B select agent with no available effective vaccine. Previous
      immunizations in mice have utilized the lipopolysaccharide (LPS) as a potential
      vaccine target because it is known as one of the most important antigenic
      epitopes in B. pseudomallei. Complicating this strategy are the four different B.
      pseudomallei LPS O-antigen types: A, B, B2, and rough. Sero-crossreactivity is
      common among O-antigens of Burkholderia species. Here, we identified the presence
      of multiple B. pseudomallei O-antigen types and sero-crossreactivity in its near
      neighbor species. RESULTS: PCR screening of O-antigen biosynthesis genes,
      phenotypic characterization using SDS-PAGE, and immunoblot analysis showed that
      majority of B. mallei and B. thailandensis strains contained the typical O
      antigen type A. In contrast, most of B. ubonensis and B. thailandensis-like
      strains expressed the atypical O-antigen types B and B2, respectively. Most B.
      oklahomensis strains expressed a distinct and non-seroreactive O-antigen type,
      except strain E0147 which expressed O-antigen type A. O-antigen type B2 was also
      detected in B. thailandensis 82172, B. ubonensis MSMB108, and Burkholderia sp.
      MSMB175. Interestingly, B. thailandensis-like MSMB43 contained a novel serotype B
      positive O-antigen. CONCLUSIONS: This study expands the number of species which
      express B. pseudomallei O-antigen types. Further work is required to elucidate
      the full structures and how closely these are to the B. pseudomallei O-antigens,
      which will ultimately determine the efficacy of the near-neighbor B serotypes for
      vaccine development.

PMID- 23126232
TI  - Gas-phase kinetics of the hydroxyl radical reaction with allene: absolute rate
      measurements at low temperature, product determinations, and calculations.
AB  - The gas phase reaction of the hydroxyl radical with allene has been studied
      theoretically and experimentally in a continuous supersonic flow reactor over the
      range 50 <= T/K <= 224. This reaction has been found to exhibit a negative
      temperature dependence over the entire temperature range investigated, varying
      between (0.75 and 5.0) * 10(-11) cm(3) molecule(-1) s(-1). Product formation from
      the reaction of OH and OD radicals with allene (C(3)H(4)) has been investigated
      in a fast flow reactor through time-of-flight mass spectrometry, at pressures
      between 0.8 and 2.4 Torr. The branching ratios for adduct formation (C(3)H(4)OH)
      in this pressure range are found to be equal to 34 +/- 16% and 48 +/- 16% for the
      OH and OD + allene reactions, respectively, the only other channel being the
      formation of CH(3) or CH(2)D + H(2)CCO (ketene). Moreover, the rate constant for
      the OD + C(3)H(4) reaction is also found to be 1.4 times faster than the rate
      constant for the OH + C(3)H(4) reaction at 1.5 Torr and at 298 K. The
      experimental results and implications for atmospheric chemistry have been
      rationalized by quantum chemical and RRKM calculations.

PMID- 23126233
TI  - Prevalence of and risk factors for MRSA colonization in HIV-positive outpatients
      in Singapore.
AB  - BACKGROUND: Whilst there have been studies on the risks and outcomes of MRSA
      colonization and infections in HIV-positive patients, local data is limited on
      the risk factors for MRSA colonization among these patients. We undertook this
      study in a tertiary HIV care centre to document the risk factors for colonization
      and to determine the prevalence of MRSA colonization among HIV-positive
      outpatients in Singapore. METHODS: This was a cross-sectional study in which
      factors associated with MRSA positivity among patients with HIV infection were
      evaluated. A set of standardized questionnaire and data collection forms were
      available to interview all recruited patients. Following the interview, trained
      nurses collected swabs from the anterior nares/axilla/groin (NAG), throat and
      peri-anal regions. Information on demographics, clinical history, laboratory
      results and hospitalization history were retrieved from medical records. RESULTS:
      MRSA was detected in swab cultures from at least 1 site in 15 patients (5.1%).
      Inclusion of throat and/or peri-anal swabs increased the sensitivity of NAG
      screening by 20%. Predictors for MRSA colonization among HIV-positive patients
      were age, history of pneumonia, lymphoma, presence of a percutaneous device
      within the past 12 months, history of household members hospitalized more than
      two times within the past 12 months, and a most recent CD4 count less than 200.
      CONCLUSIONS: This study highlights that a proportion of MRSA carriers would have
      been undetected without multiple-site screening cultures. This study could shed
      insight into identifying patients at risk of MRSA colonization upon hospital
      visit and this may suggest that a risk factor-based approach for MRSA
      surveillance focusing on high risk populations could be considered.

PMID- 23126234
TI  - Emerging cell-cycle inhibitors for pancreatic cancer therapy.
AB  - INTRODUCTION: Patients with pancreatic cancer (PC) present with advanced disease
      that is lethal and notoriously difficult to treat. The research focused initially
      on combining cytotoxic therapies with gemcitabine, and over the past decade, a
      large number of studies have been published that aimed to target the molecular
      abnormalities implicated in pancreatic tumor growth. AREAS COVERED: The cell
      cycle is a tightly regulated series of events that governs cell replication and
      division. Deregulation of cell cycle kinases have been implicated in PC
      tumorigenesis. In this review, we discuss the potential and limitations of
      current cyclin-kinase inhibitors. We also summarize progress in evaluating other
      mitotic kinase inhibitors and novel cell-cycle kinase inhibitors as potential
      therapeutic agents in PC. EXPERT OPINION: While the successful development and
      approval of cell-cycle inhibitors for PC therapy remains unresolved, pre-clinical
      identification of resistant mechanisms would help design better early- phase
      clinical trials where relevant combinations may be evaluated prior to Phase II
      testing. The authors believe that cell-cycle kinases are important anti-cancer
      targets that operate in collaboration with other oncogenes intimately involved in
      uncontrolled tumor proliferation and by providing a unique, targeted, and
      complimentary anti-cancer mechanism, expand the available armamentarium against
      PC.

PMID- 23126235
TI  - Hair fiber as a nanoreactor in controlled synthesis of fluorescent gold
      nanoparticles.
AB  - The synthesis and detailed characterization of gold nanoparticles (AuNPs) inside
      human hair has been achieved by treatment of hair with HAuCl(4) in alkaline
      medium. The AuNPs, which show a strong red fluorescence under blue light, are
      generated inside the fiber and are arranged in the cortex in a remarkably regular
      pattern of whorls based on concentric circles, like a fingerprint. It opens an
      area of genuine nanocomposites with novel properties due to AuNPs inside the hair
      shaft.

PMID- 23126236
TI  - Relationship between anti-apoptotic proteins survivin and Bcl-2, and response to
      treatment in patients undergoing post-operative RT for laryngeal cancer: a pilot
      study.
AB  - BACKGROUND: Clinicopathological research has focused on identifying molecular and
      biological prognostic factors for laryngeal carcinoma (LSCC) treated with post
      operative radiotherapy (RT). The aim of this study was to assess the prognostic
      importance of anti-apoptotic proteins survivin and B-cell lymphoma-2 (Bcl-2) in a
      series of patients with LSCC who had primary surgery followed by RT. METHODS:
      Thirty-three consecutive patients who underwent primary surgery followed by RT
      were considered. Survivin nuclear and cytoplasmic expressions and Bcl-2
      expression were determined immunohistochemically. RESULTS: The loco-regional
      recurrence rate was significantly higher among LSCC patients with a nuclear
      survivin expression >10.0% (P = 0.029), and their disease-free survival (DFS) was
      shorter than in cases whose nuclear survivin expression was <=10.0% (P = 0.002).
      DFS was significantly shorter in cases with a Bcl-2 expression >2.0% than in
      those whose Bcl-2 expression was <=2.0% (P = 0.035). CONCLUSIONS: Nuclear
      survivin expression and Bcl-2 expression warrant further investigation as
      potential predictive biomarkers to enable individualized treatments (e.g. post
      operative chemo-radiotherapy instead of RT alone for patients whose LSCCs
      strongly express nuclear survivin or/and Bcl-2). This preliminary evidence
      justifies the design of new studies on the association of agents targeting
      survivin and Bcl-2 with conventional chemotherapeutic agents and RT for advanced
      LSCC.

PMID- 23126237
TI  - Budesonide/formoterol maintenance and reliever therapy via Turbuhaler versus
      fixed-dose budesonide/formoterol plus terbutaline in patients with asthma: phase
      III study results.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the efficacy and tolerability of
      budesonide/formoterol as maintenance and reliever therapy versus
      budesonide/formoterol maintenance plus terbutaline in adults with persistent
      asthma not adequately controlled with inhaled corticosteroid (ICS) therapy alone.
      METHODS: In this 12-month, randomized, double-blind, parallel-group, phase III
      study (NCT00839800), patients (age >= 16 years; receiving maintenance ICS; >= 1
      severe exacerbation in the 12 months prior to study entry) were randomized to
      either budesonide/formoterol 160/4.5 MUg 1 inhalation twice daily plus
      budesonide/formoterol 160/4.5 MUg as-needed or budesonide/formoterol 160/4.5 MUg
      1 inhalation twice daily plus terbutaline 0.4 mg as-needed for 12 months. PRIMARY
      OUTCOME: time to first severe asthma exacerbation; secondary outcomes included:
      lung function, asthma symptom variables and tolerability. RESULTS: Two thousand
      and ninety-one patients were randomized: 170 (16%) receiving
      budesonide/formoterol maintenance and reliever therapy experienced 259 severe
      exacerbations versus 229 patients (22%) receiving budesonide/formoterol plus
      terbutaline who experienced 363 severe exacerbations. Budesonide/formoterol
      maintenance and reliever therapy prolonged the time to first severe exacerbation
      versus budesonide/formoterol plus terbutaline (P = 0.0007) and reduced the
      instantaneous risk of an exacerbation by 30% (hazard ratio 0.70, 95% confidence
      interval 0.57-0.85, P = 0.0003). Times to first oral steroid use, first
      hospitalization and first emergency room treatment were all significantly
      prolonged in the budesonide/formoterol maintenance and reliever group versus
      budesonide/formoterol plus terbutaline. Both treatment groups were well
      tolerated. CONCLUSIONS: Budesonide/formoterol maintenance and reliever therapy
      provided more effective asthma control, including a prolonged time to first
      severe asthma exacerbation, than budesonide/formoterol plus terbutaline and was
      well tolerated. Budesonide/formoterol maintenance and reliever therapy also
      improved lung function and asthma symptoms.

PMID- 23126238
TI  - Essential oil variation in the populations of Artemisia spicigera from northwest
      of Iran: chemical composition and antibacterial activity.
AB  - CONTEXT: Artemisia spicigera C. Koch (Asteraceae) is a perennial shrubby herb and
      is generally distributed in Armenia, Iran, and Middle Anatolia. This species
      traditionally has been used in medicines. OBJECTIVE: The aim of this research is
      to study the chemical composition and antibacterial activity of essential oils
      from Artemisia spicigera populations in northwest of Iran. MATERIALS AND METHODS:
      The essential oil of A. spicigera was obtained by hydrodistillation from eight
      populations collected from different regions of East Azerbaijan and West
      Azerbaijan provinces (Iran) and analyzed by gas chromatography-mass spectrometry
      (GC-MS). The antibacterial activity of the oils was investigated against four
      Gram-positive and four Gram-negative bacteria using MIC determinations and the
      agar-gel diffusion method. RESULTS: Fourteen compounds were identified as the
      main components of the essential oils and the most abundant constituents are 1,8
      cineole, camphor, alpha-thujone, camphene, beta-thujone and p-cymene. Essential
      oil of population No. 1 showed the highest activity against Escherichia coli,
      Enterobacter aerogenes, Serratia marcescens and Staphylococcus aureus but the
      highest activity against St. saprophyticus, Bacillus megaterium, and B. cereus
      was found with population No. 6 and for Citrobacter amalonaficus with population
      No. 5. MIC values of essential oils ranged from 6 ug/mL against Bacillus
      megaterium to 12 ug/mL against Citrobacter amalonaficus. DISCUSSION: This study
      demonstrates the occurrence of 1,8-cineole/camphor/camphene chemotype of A.
      spicigera but there is also significant chemical variation between the studied
      populations. The findings showed the studied oils have good antibacterial
      activity, and thus potential to be used as natural health products.

PMID- 23126240
TI  - Fatal accidental hydrogen sulfide poisoning: a domestic case.
AB  - Hydrogen sulfide (H(2)S) poisonings are classically reported in occupational
      settings. We describe an unusual domestic case of fatal acute poisoning by H(2)S
      inhalation. A mother and her infant daughter were found dead in the kitchen of
      their home. The emergency medical team described a strong smell of rotten eggs,
      suggesting acute H(2)S poisoning. Autopsies revealed only multiorgan congestion.
      H(2) S was measured in blood and lung tissue samples by gas chromatography/mass
      spectrometry. Body fluids were negative, but H(2) S was found in the lungs of
      both the mother and the child at concentrations of 1.46 and 1.92 mg/kg,
      respectively, concentrations described in the literature as potentially lethal.
      Expert surveys of the premises suggested a complex mechanism involving both
      defective maintenance of the pipes and drains of the building and faulty assembly
      of the sink siphon, which led to stagnation of waste water and formation of a
      pocket of H(2)S.

PMID- 23126239
TI  - Analysis of grey matter in thalamus and basal ganglia based on EEG alpha3/alpha2
      frequency ratio reveals specific changes in subjects with mild cognitive
      impairment.
AB  - GM (grey matter) changes of thalamus and basal ganglia have been demonstrated to
      be involved in AD (Alzheimer's disease). Moreover, the increase of a specific EEG
      (electroencephalogram) marker, alpha3/alpha2, have been associated with AD
      converters subjects with MCI (mild cognitive impairment). To study the
      association of prognostic EEG markers with specific GM changes of thalamus and
      basal ganglia in subjects with MCI to detect biomarkers (morpho-physiological)
      early predictive of AD and non-AD dementia. Seventy-four adult subjects with MCI
      underwent EEG recording and high-resolution 3D MRI (three-dimensional magnetic
      resonance imaging). The alpha3/alpha2 ratio was computed for each subject. Three
      groups were obtained according to increasing tertile values of alpha3/alpha2
      ratio. GM density differences between groups were investigated using a VBM (voxel
      based morphometry) technique. Subjects with higher alpha3/alpha2 ratios when
      compared with subjects with lower and middle alpha3/alpha2 ratios showed minor
      atrophy in the ventral stream of basal ganglia (head of caudate nuclei and
      accumbens nuclei bilaterally) and of the pulvinar nuclei in the thalamus; The
      integrated analysis of EEG and morpho-structural markers could be useful in the
      comprehension of anatomo-physiological underpinning of the MCI entity.

PMID- 23126241
TI  - Abdominal ultrasonography of the normal St. Kitts vervet monkey (Chlorocebus
      sabaeus).
AB  - BACKGROUND: Normal ultrasonography of non-reproductive abdominal and male
      reproductive anatomy in the vervet monkey were prospectively assessed. This has
      not been previously reported. METHODS: Ten non-sexually active male and 10 non
      gravid female clinically healthy vervet monkeys between 5 and 12 years of age and
      weighing between 3.13 and 6.85 kg were evaluated with ultrasound. Individuals
      were randomly divided by gender groups into one of two immobilization protocols
      and scanned at 18.0 MHz. RESULTS: High-quality images of the liver, gallbladder,
      kidneys, urinary bladder, spleen, adrenal glands, gastrointestinal tract, and
      testes were acquired. The prostate was never visualized. Abdominal lymph nodes
      other than an ileocolic, the pancreas, and the female reproductive tract were not
      evaluated. Gastric and duodenal motility were significantly different between
      immobilization protocols (P<0.05). CONCLUSIONS: Abdominal sonographic anatomy was
      successfully characterized and normal size parameters for non-reproductive
      abdominal viscera and the testes were established.

PMID- 23126242
TI  - High-fidelity simulation is superior to case-based discussion in teaching the
      management of shock.
AB  - BACKGROUND: Case-based discussion (CBD) is an established method for active
      learning in medical education. High-fidelity simulation has emerged as an
      important new educational technology. There is limited data from direct
      comparisons of these modalities. AIMS: The primary purpose of this study was to
      compare the effectiveness of high-fidelity medical simulation with CBD in an
      undergraduate medical curriculum for shock. METHODS: The subjects were 85 third
      year medical students in their required surgery rotation. Scheduling
      circumstances created two equal groups. One group managed a case of septic shock
      in simulation and discussed a case of cardiogenic shock, the other group
      discussed septic shock and experienced cardiogenic shock through simulation.
      Student comprehension of the assessment and management of shock was then
      evaluated by oral examination (OE). RESULTS: Examination scores were superior in
      all comparisons for the type of shock experienced through simulation. This was
      true regardless of the shock type. Scores associated with patient evaluation and
      invasive monitoring, however, showed no difference between groups or in crossover
      comparison. CONCLUSIONS: In this study, students demonstrated better
      understanding of shock following simulation than after CBD. The secondary finding
      was the effectiveness of an OE with just-in-time deployment in curriculum
      assessment.

PMID- 23126243
TI  - Determining measures of insight and foresight from responses to multiple choice
      questions.
AB  - BACKGROUND: Clinical decisions require insight and foresight. When these are
      lacking, overconfidence and error can occur. AIMS: Multiple choice questions
      (MCQ) responses were used to estimate insight, as determined by confidence in
      responses, and foresight, as determined by the safety of incorrect responses.
      METHODS: An MCQ response system was developed which reflected confidence in, and
      safeness of, responses. An optional examination incorporating this system was
      offered to medical students at one university. RESULTS: A total of 372 students
      completed the study. There was evidence of insight. The proportion of responses
      that were correct rose from 32% for low confidence to 77% for high confidence.
      The proportion that was incorrect and not unsafe fell from 34% for low confidence
      to 7% for high confidence. There was less evidence of foresight. Of the responses
      that were incorrect, the proportion that was unsafe increased from 52% for low
      confidence to 68% for high confidence. Measures of insight and foresight
      increased with experience. Students with poorer knowledge chose more unsafe
      responses, but with lower confidence. Five students gave multiple highly unsafe
      responses held with high confidence. CONCLUSIONS: Students had insight but less
      foresight. Experience and knowledge altered measures of both. This response
      system identified students who appeared to lack both.

PMID- 23126244
TI  - Medical versus surgical termination of pregnancy in primigravid women--is the
      next delivery differently at risk? A population-based register study.
AB  - OBJECTIVE: To compare the effect of medical versus surgical termination of
      pregnancy (TOP), performed in primigravid women, on subsequent delivery. DESIGN:
      Population-based register study. SETTING: Finland 2000-2009. POPULATION: All
      primigravid women (n = 8294) who underwent TOP during first trimester of
      pregnancy by medical (n = 3441) or surgical (n = 4853) method, and whose
      subsequent pregnancy resulted in singleton delivery. METHODS: The women were
      identified in the Finnish Register of Induced Abortions, and the data were linked
      to the Medical Birth and the Hospital Discharge Registries. MAIN OUTCOME
      MEASURES: Risk of preterm birth, low birthweight, small-for-gestational-age (SGA)
      infant and placental complications (placenta praevia, placental abruption,
      retained placenta, placenta accreta). RESULTS: No statistically significant
      differences in the incidences of preterm birth (4.0% in the medical group versus
      4.9% in the surgical group), low birthweight (3.4% versus 4.0%), SGA infants
      (2.6% versus 2.9%) or placental complications (2.6% versus 2.8%) emerged between
      the two groups. After adjusting for various background factors, medical TOP was
      not associated with significantly altered risks of preterm birth (odds ratio [OR]
      0.87, 95% confidence interval [95% CI] 0.68-1.13), low birthweight (OR 0.90, 95%
      CI 0.68-1.19), SGA infant (OR 0.87, 95% CI 0.64-1.20) or placental complications
      (OR 0.98, 95% CI 0.72-1.34) versus surgical TOP. In a sub-analysis excluding
      women who underwent surgical evacuation following the index TOP, medical TOP was
      associated with a reduced risk of preterm birth (P < 0.01), but the difference
      became insignificant after adjusting for gestational age at the time of TOP,
      inter-pregnancy interval, maternal age, cohabitation status, socio-economic
      status, residence and smoking during pregnancy. CONCLUSIONS: A history of one
      medical versus surgical TOP, performed in primigravid women, is associated with
      similar obstetric risks in the subsequent delivery.

PMID- 23126246
TI  - Calling all pharmacologists with time to spare! We need you! Build the drug
      discovery knowledge base, GuidetoPharmacology.org.

PMID- 23126247
TI  - Why is publication of negative clinical trial data important?

PMID- 23126245
TI  - Renal pericytes: regulators of medullary blood flow.
AB  - Regulation of medullary blood flow (MBF) is essential in maintaining normal
      kidney function. Blood flow to the medulla is supplied by the descending vasa
      recta (DVR), which arise from the efferent arterioles of juxtamedullary
      glomeruli. DVR are composed of a continuous endothelium, intercalated with smooth
      muscle-like cells called pericytes. Pericytes have been shown to alter the
      diameter of isolated and in situ DVR in response to vasoactive stimuli that are
      transmitted via a network of autocrine and paracrine signalling pathways.
      Vasoactive stimuli can be released by neighbouring tubular epithelial,
      endothelial, red blood cells and neuronal cells in response to changes in NaCl
      transport and oxygen tension. The experimentally described sensitivity of
      pericytes to these stimuli strongly suggests their leading role in the phenomenon
      of MBF autoregulation. Because the debate on autoregulation of MBF fervently
      continues, we discuss the evidence favouring a physiological role for pericytes
      in the regulation of MBF and describe their potential role in tubulo-vascular
      cross-talk in this region of the kidney. Our review also considers current
      methods used to explore pericyte activity and function in the renal medulla.

PMID- 23126248
TI  - Redox-dependent stability of the gamma-glutamylcysteine synthetase enzyme of
      Escherichia coli: a novel means of redox regulation.
AB  - Glutathione is a thiol-containing tripeptide that plays important roles in redox
      related processes. The first step in glutathione biosynthesis is catalysed by
      gamma-GCS (gamma-glutamylcysteine synthetase). The crystal structure of
      Escherichia coli gamma-GCS has revealed the presence of a disulfide bond. As the
      disulfide-bonding cysteine residues Cys372 and Cys395 are not well conserved
      among gamma-GCS enzymes in this lineage, we have initiated a biochemical genetic
      strategy to investigate the functional importance of these and other cysteine
      residues. In a cysteine-free gamma-GCS that was non-functional, suppressor
      analysis yielded combinations of cysteine and aromatic residues at the position
      of the disulfide bond, and one mutant that lacked any cysteine residues. Kinetic
      analysis of the wild-type and mutant enzymes revealed that the disulfide bond was
      not involved in determining the affinity of the enzyme towards its substrate, but
      had an important role in determining the stability of the protein, and its
      catalytic efficiency. We show that in vivo the gamma-GCS enzyme can also exist in
      a reduced form and that the mutants lacking the disulfide bond show a decreased
      half-life. These results demonstrate a novel means of regulation of gamma-GCS by
      the redox environment that works by an alteration in its stability.

PMID- 23126249
TI  - DHEA and intracrinology at menopause, a positive choice for evolution of the
      human species.
AB  - Menopause has been chosen by evolution as the convergence of three factors,
      namely cessation of ovarian function (reproduction and estrogen secretion), high
      circulating dehydroepiandrosterone (DHEA), and intracrine enzymes able to convert
      DHEA into active sex steroids in peripheral tissues. The arrest of estrogen
      secretion by the ovaries at menopause causes a decrease of circulating estradiol
      below the threshold of biological activity, thus eliminating stimulation of the
      endometrium and risk of endometrial cancer. As much as the arrest of secretion of
      estradiol by the ovaries is essential to protect the uterus, it is of major
      importance that sex steroids continue to be made available in most other tissues
      which need estrogens and/or androgens for their normal functioning. Evolution,
      through 500 million years, has progressively provided the peripheral tissues with
      the enzymes able to make androgens and estrogens while high levels of DHEA, the
      precursor of all sex steroids, have appeared much later with the primates
      approximately 20 million years ago. All elements were thus in place for the
      functioning of intracrinology or the cell-specific formation of estrogens and
      androgens in peripheral tissues from the inactive precursor DHEA, with no
      significant release of active sex steroids in the circulation, thus eliminating
      the risks of adverse effects in the other tissues, especially the uterus. The
      presence of subthreshold levels of circulating estradiol combined with the
      formation of sex steroids from DHEA in specific peripheral tissues
      (intracrinology) makes menopause a positive characteristic supporting many years
      of good-quality postmenopausal life, useful for taking care of children and
      grandchildren. DHEA, however, decreases with age and is present at very different
      concentrations between different women, with the consequence that approximately
      75% of postmenopausal women have too low circulating DHEA levels and suffer from
      symptoms/signs of hormone deficiency.

PMID- 23126250
TI  - Emerging therapies for gout.
AB  - INTRODUCTION: Gout is the commonest inflammatory arthritis in adults that affects
      4% of the US population. Gout is symptomatic, leading to joint pain and
      inflammation, frequent acute flares associated with disability, pain and
      suffering. When not treated optimally, chronic inflammation can lead to chronic
      pain, joint destruction and deformities and decrements in function and quality of
      life. AREAS COVERED: Different therapeutic strategies that are being developed in
      preclinical and clinical settings are discussed. EXPERT OPINION: Multiple new
      treatment approaches have emerged for gout. Several target acute inflammation of
      gout flares by inhibiting interleukin-1, either with an antibody or with a
      molecule that traps interleukin-1. Two drugs in this category are rilonacept and
      canakinumab. Similarly, new approaches targeting and increasing urate excretion
      by the kidney are emerging. One such promising drug is lesinurad that decreases
      serum urate through inhibition of the uric acid transporter (URAT1) in the
      proximal tubule of the kidney. We hope these and other new treatments and new
      strategies for gout will lead to additional options. The expansion of the
      armamentarium for gout treatment will allow clinicians and patients to increase
      the chances to have gout remission.

PMID- 23126251
TI  - Antifungal activity of the Algerian Lawsonia inermis (henna).
AB  - CONTEXT: Lawsonia inermis Linn. (Lythraceae) or henna has been used since the
      earliest times as a medicine, preservative, and cosmetic. It has long been
      recommended in traditional medicine as an astringent, purgative, and
      abortifacient. OBJECTIVE: Lawsone and six extracts of L. inermis plant, used by
      Algerian traditional healers to treat infectious diseases, were screened for
      their antifungal activity against filamentous fungi. MATERIALS AND METHODS: Water
      and five organic extracts - DMSO, ethanol, chloroform, ethyl acetate, and di
      ethyl ether - of L. inermis leaves, collected in the area of Adrar (Algeria),
      were prepared by soaking 25 g of powdered plant in 100 mL of solvent. The
      extracts were screened for antifungal activity using the poisoned food technique
      against five filamentous fungi. RESULTS: Results demonstrated that the best yield
      (8.03%) was obtained with the ethanol extract. The commercial lawsone showed
      potentially interesting MICs against the strains Fusarium oxysporum (12 ug/mL)
      and Aspergillus flavus (50 ug/mL). The ethanol extract showed the only
      interesting MIC (230 ug/mL of crude extract) against the strain F. oxysporum
      compared with other extracts. DISCUSSION AND CONCLUSION: These results suggest
      that the Algerian L. inermis plant has antifungal activity that can be related to
      the presence of lawsone in the leaves plant. The results can be exploited largely
      in research of new antifungal drugs.

PMID- 23126254
TI  - HDR brachytherapy combined with interstitial hyperthermia in locally advanced
      cervical cancer patients initially treated with concomitant radiochemotherapy: a
      phase I study.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to investigate whether
      hyperthermia (HT) combined with interstitial brachytherapy (ISBT) has any
      influence on acute and late side effects in patients with advanced cervical
      cancer. Local control (LC) and disease-free survival (DFS) were also analysed.
      MATERIALS AND METHODS: Following the completion of radiochemotherapy, patients
      with cervical cancer (FIGO stages I-III) were assigned to two treatment groups,
      either ISBT combined with interstitial hyperthermia (ISHT) or ISBT alone as a
      control group. Selection criterion for the ISBT combined with HT group was
      advanced cervical cancer with poor response to external beam radiotherapy. A
      total of 76 patients were included in the statistical analysis. Once a week, HT
      (at a temperature above 42.5 degrees C) was administered for 45 min before and
      during high dose rate (HDR) brachytherapy (BT) in 43 patients. Four HT treatments
      were administered. RESULTS: The median follow-up time was 43 months (range 4-73
      months). Significant differences were not observed for the distribution of early
      and late complications between the HT and no HT groups. Despite this, LC was
      similar in both groups. The 5-year DFS for the BT and BT + HT groups was 73.6%
      and 65.8%, respectively. The 5-year LC for the BT and BT + HT groups was 89% and
      83%, respectively. For the majority of patients the maximum temperature level of
      44-45 degrees C was achieved during the ISHT. CONCLUSIONS: ISHT is well tolerated
      and does not affect treatment-related early or late complications.

PMID- 23126253
TI  - Benzodiazepine dependence and its treatment with low dose flumazenil.
AB  - Globally benzodiazepines remain one of the most prescribed medication groups,
      especially in the primary care setting. With such high levels of prescribing it
      is not surprising that benzodiazepine dependence is common, cutting across all
      socioeconomic levels. Despite recognition of the potential for the development of
      iatrogenic dependence and the lack of any effective treatment, benzodiazepines
      continue to be widely prescribed in general practice. Conventional dependence
      management, benzodiazepine tapering, is commonly a protracted process over
      several weeks or months. It is often associated with significant withdrawal
      symptoms and craving leading to patient drop out and return to use. Accordingly,
      there is a worldwide need to find effective pharmacotherapeutic interventions for
      benzodiazepine dependence. One drug of increasing interest is the GABAA
      benzodiazepine receptor antagonist/partial agonist, flumazenil. Multiple bolus
      intravenous infusions of low dose flumazenil used either with or without
      benzodiazepine tapering can reduce withdrawal sequelae, and/or longer term
      symptoms in the months following withdrawal. Preliminary data suggest that
      continuous intravenous or subcutaneous flumazenil infusion for 4 days
      significantly reduces acute benzodiazepine withdrawal sequelae. The subcutaneous
      infusion was shown to be tissue compatible so the development of a longer acting
      (i.e. several weeks) depot flumazenil formulation has been explored. This could
      be capable of managing both acute and longer term benzodiazepine withdrawal
      sequelae. Preliminary in vitro water bath and in vivo biocompatibility data in
      sheep show that such an implant is feasible and so is likely to be used in
      clinical trials in the near future. 

PMID- 23126255
TI  - Increased titers of neutralizing antibodies after immunization with both envelope
      proteins of the porcine endogenous retroviruses (PERVs).
AB  - Despite enormous difficulties to induce antibodies neutralizing HIV-1, especially
      broadly neutralizing antibodies directed against the conserved membrane proximal
      external region (MPER) of the transmembrane envelope protein, such antibodies can
      be easily induced in the case of gammaretroviruses, among them the porcine
      endogenous retroviruses (PERVs). In addition to neutralizing antibodies directed
      against the transmembrane envelope protein p15E, neutralizing antibodies were
      also induced by immunization with the surface envelope protein gp70. PERVs
      represent a special risk for xenotransplantation using pig tissues or organs
      since they are integrated in the genome of all pigs and infect human cells and a
      vaccine may protect from transmission to the recipient. To investigate the effect
      of simultaneous immunization with both proteins in detail, a study was performed
      in hamsters. Gp70 and p15E of PERV were produced in E. coli, purified and used
      for immunization. All animals developed binding antibodies against the antigens
      used for immunization. Sera from animals immunized with p15E recognized epitopes
      in the MPER and the fusion peptide proximal region (FPPR) of p15E. One MPER
      epitope showed a sequence homology to an epitope in the MPER of gp41 of HIV-1
      recognized by broadly neutralizing antibodies found in HIV infected individuals.
      Neutralizing antibodies were detected in all sera. Most importantly, sera from
      animals immunized with gp70 had a higher neutralizing activity when compared with
      the sera from animals immunized with p15E and sera from animals immunized with
      gp70 together with p15E had a higher neutralizing activity compared with sera
      from animals immunized with each antigen alone. These immunization studies are
      important for the development of vaccines against other retroviruses including
      the human immunodeficiency virus HIV-1.

PMID- 23126256
TI  - Characterization of UDP-glucuronosyltransferases involved in glucuronidation of
      diethylstilbestrol in human liver and intestine.
AB  - Diethylstilbestrol (DES), a synthetic estrogen, is famous for its carcinogenic
      effects. Human exposure to this compound can occur frequently through dietary
      ingestion and medical treatment. Glucuronidation has been demonstrated to be a
      predominant metabolic pathway for DES in human. Therefore, glucuronidation
      metabolism may have a significant impact on its toxicities, and it is essential
      to clarify this metabolic pathway. Accordingly, this in vitro study is designed
      to characterize the UGTs involved in DES glucuronidation and, furthermore, to
      identify the roles of individual isoforms in the reaction in liver and intestine.
      Human liver microsomes (HLM) displayed much higher potential for DES
      glucuronidation than human intestinal microsomes (HIM). The intrinsic clearances
      in HLM and HIM were demonstrated to be 459 and 14 MUL/min/mg protein,
      respectively. Assays with recombinant UGTs demonstrated that UGT1A1, -1A3, -1A8,
      and -2B7 could catalyze DES glucuronidation, among which UGT2B7 showed the
      highest affinity. Chemical inhibitors of UGT2B7 and UGT1A1/1A3 both displayed
      similar inhibition against the reaction in UGT2B7 and HLM. In addition, DES
      glucuronidation in individual HLM exhibited a large individual variability and
      strongly correlated to UGT2B7 activity. All evidence indicates that UGT2B7 may
      act as a major enzyme responsible for DES glucuronidation in human liver. For
      HIM, both UGT2B7 inhibitor and UGT1A1/1A3/1A8 inhibitor exerted moderate
      inhibition. It is suggested that although UGT2B7 contributes to DES
      glucuronidation in intestine, other UGTs may contribute equally. In summary, this
      study characterizes human UGTs involved in DES glucuronidation in human liver and
      intestine, which may be helpful for further study about DES-related toxicities.

PMID- 23126258
TI  - Visuospatial asymmetry in dual-task performance after subacute stroke.
AB  - Various authors have referred to an association between neglect and non-spatial
      components of attention. It has been suggested that an increase in attentional
      load could exacerbate neglect symptoms and reveal subtle, well-compensated
      neglect. In the present study, 21 RH and 22 LH subacute stroke patients and 20
      controls performed a computerized single-detection task (CVRT) and a dual task
      (CVRT-D) combining the detection task with a driving simulation task. Omissions,
      reaction times (RTs) and RT asymmetries were analysed to investigate the
      influence of increasing attentional load on neglect symptoms. RT asymmetries were
      most pronounced in RH patients. Although a clear increase in RT asymmetries
      between CVRT and CVRT-D was observed, the amount of increase did not differ
      between both patient groups. Within both patient groups, correlations between RT
      asymmetries and ipsilesional RTs as a measure of general attention were
      significant in the single task but not in the dual task, indicating that
      increased attentional load may result in different degrees of lateralized and
      general attentional problems. Half of the patients with neglect on the BIT
      (Behavioural Inattention Test) showed increased RT asymmetries from CVRT to CVRT
      D. Moreover, two LH and RH patients without neglect symptoms on the BIT and CVRT
      showed distinctively increased asymmetries in the CVRT-D, fostering the idea of
      an emergence of subtle neglect under increased attentional load. Dual-task
      performance may draw attention towards patients who, without obvious signs of
      neglect, may show visuospatial attention deficits in complex situations.

PMID- 23126257
TI  - Functional characterization of long-chain prenyl diphosphate synthases from
      tomato.
AB  - The electron transfer molecules plastoquinone and ubiquinone are formed by the
      condensation of aromatic head groups with long-chain prenyl diphosphates. In the
      present paper we report the cloning and characterization of two genes from tomato
      (Solanum lycopersicum) responsible for the production of solanesyl and decaprenyl
      diphosphates. SlSPS (S. lycopersicum solanesyl diphosphate synthase) is targeted
      to the plastid and both solanesol and plastoquinone are associated with thylakoid
      membranes. A second gene [SlDPS (S. lycopersicum solanesyl decaprenyl diphosphate
      synthase)], encodes a long-chain prenyl diphosphate synthase with a different
      subcellular localization from SlSPS and can utilize geranyl, farnesyl or
      geranylgeranyl diphosphates in the synthesis of C45 and C50 prenyl diphosphates.
      When expressed in Escherichia coli, SlSPS and SlDPS extend the prenyl chain
      length of the endogenous ubiquinone to nine and ten isoprene units respectively.
      In planta, constitutive overexpression of SlSPS elevated the plastoquinone
      content of immature tobacco leaves. Virus-induced gene silencing showed that
      SlSPS is necessary for normal chloroplast structure and function. Plants silenced
      for SlSPS were photobleached and accumulated phytoene, whereas silencing SlDPS
      did not affect leaf appearance, but impacted on primary metabolism. The two genes
      were not able to complement silencing of each other. These findings indicate a
      requirement for two long-chain prenyl diphosphate synthases in the tomato.

PMID- 23126259
TI  - Ambulatory oximetry fails to predict survival in chronic obstructive pulmonary
      disease with mild-to-moderate hypoxaemia.
AB  - BACKGROUND AND OBJECTIVE: Although long-term oxygen therapy is one of few
      treatments known to improve survival in COPD, no patient subgroup likely to
      derive benefit has been identified in over 30 years. We assessed the prognostic
      value of point measurement of P(a) O(2) and proportion of ambulatory oximetry
      with saturations below 90% in this context. METHODS: Subjects were community
      living patients with COPD and P(a) O(2) 56-70 mm Hg when stable. Baseline
      assessments included clinical, physiological and laboratory assessments, as well
      as 24-h ambulatory oximetry. Patients were followed to death from any cause,
      first exacerbation and first admission. RESULTS: Despite poor survival overall,
      there was no significant difference in prognosis between mildly hypoxaemic and
      moderately hypoxaemic patients. There were also no significant differences for
      secondary end-points (exacerbation and hospital admission). On multivariate
      analysis, trends were observed towards improved survival, with higher P(a) O(2)
      and greater proportion of ambulatory oximetry below 90%. CONCLUSIONS: Neither
      resting P(a) O(2) nor proportion of ambulatory oximetry below 90% saturation
      effectively predicted survival in COPD.

PMID- 23126261
TI  - Catalyst-free growth of millimeter-long topological insulator Bi2Se3 nanoribbons
      and the observation of the pi-Berry phase.
AB  - We report the growth of single-crystalline Bi(2)Se(3) nanoribbons with lengths up
      to several millimeters via a catalyst-free physical vapor deposition method.
      Scanning transmission electron microscopy analysis reveals that the nanoribbons
      grow along the (1120) direction. We obtain a detailed characterization of the
      electronic structure of the Bi(2)Se(3) nanoribbons from measurements of Shubnikov
      de Haas (SdH) quantum oscillations. Angular dependent magneto-transport
      measurements reveal a dominant two-dimensional contribution originating from
      surface states. The catalyst-free synthesis yields high-purity nanocrystals
      enabling the observation of a large number of SdH oscillation periods and
      allowing for an accurate determination of the pi-Berry phase, one of the key
      features of Dirac fermions in topological insulators. The long-length nanoribbons
      open the possibility for fabricating multiple nanoelectronic devices on a single
      nanoribbon.

PMID- 23126260
TI  - Impact of electroacupuncture on quality of life for patients with Relapsing
      Remitting Multiple Sclerosis under treatment with immunomodulators: a randomized
      study.
AB  - BACKGROUND: Multiple sclerosis (MS) is a complex autoimmune disease mediated by
      an immune response to central nervous system antigens. Modern immunomodulatory
      therapies, however, do not ameliorate many of the symptoms, such as pain and
      depression. Patients thus seek alternative treatments, such as acupuncture,
      although the benefits of such treatments have not been objectively evaluated. The
      present study was thus designed to evaluate the effect of the use of acupuncture
      in the alleviation of the symptoms of patients with MS. METHODS: Thirty-one
      patients with Relapsing-Remitting Multiple Sclerosis undergoing treatment with
      immunomodulators were randomly distributed into sex-stratified experimental and
      placebo groups in a patient- and evaluator-blind design; they received either
      true or sham electroacupuncture during regular visits to the doctor in the
      university hospital outpatient clinic. Standardized questionnaires were used to
      evaluate the effect of electroacupuncture on the quality of life of these
      patients. Initial and follow-up assessment included the evaluation of clinical
      status (Expanded Disability Status Scale), pain (Visual Analogue Scale) and
      quality of life (Functional Assessment of multiple Sclerosis) to ascertain the
      impact of electroacupuncture on the quality of life of these patients. RESULTS:
      Electroacupuncture improved various aspects of quality of life, including a
      reduction in pain and depression. The self-report scales were more sensitive to
      improvement than was the more objective clinical measure. CONCLUSION: This paper
      provides evidence that electroacupuncture can significantly improve the quality
      of life of such patients. The results suggest that the routine use of a self
      report scale evaluating quality of life should be included in regular clinical
      evaluations in order to detect changes more rapidly. TRIAL REGISTRATION: RBR
      58yq52.

PMID- 23126262
TI  - Forensic identification of seal oils using lipid profiles and statistical models.
AB  - Seal blubber oils are used as a source of omega-3 polyunsaturated fatty acids in
      Canada but prohibited in the United States and (FA) European Union. Thus, a
      reliable method is needed to identify oils originating from seals versus fish.
      Two lipid profiling methods, fatty acid analysis using gas chromatography and
      triacylglycerol (TAG) analysis using liquid chromatography and mass spectrometry,
      were applied with statistical models to discriminate commercial oils and blubber
      samples harvested from marine fish and seals. Significant differences were
      observed among FA profiles, and seal samples differed from each of the fish oils
      (p <= 0.001). FA and TAG profiles were used to discriminate sample groups using a
      random forest classifier; all samples were classified correctly as seals versus
      fish using both methods. We propose a two-step method for the accurate
      identification of seal oils, with preliminary identification based on FA profile
      analysis and confirmation with TAG profiles. 

PMID- 23126263
TI  - Crystal packing effects on the magnetic slow relaxation of Tb(III)-nitronyl
      nitroxide radical cyclic dinuclear clusters.
AB  - Four lanthanide-based nitronyl nitroxide radical cyclic molecular clusters of
      formula [Ln(hfac)3(NITPhPO(OEt)2)]2 (Ln(III) = Gd (1), Tb (2A and 2B), and Dy (3)
      and NITPhPO(OEt)2 = 4'-[2-(1-oxyl-3-4,4,5,5
      tetramethylimidazoline)phenyl]diethoxylphosphine oxide) have been synthesized.
      Their X-ray structures have been solved and highlight two different crystal
      packings. For the particular case of the Tb(III) derivative, both of them can be
      obtained. In 2A, the molecules are well-isolated, while 2B shows short contacts
      between N-O radical groups. Static magnetic studies on the Gd(III) derivative (1)
      demonstrate that lanthanides and radicals are ferromagnetically coupled (J = 3.46
      +/- 0.04 cm(-1)). Dynamic magnetic studies show that both compounds 2A and 2B
      exhibit single molecule magnet behavior. A comparison of their magnetic behaviors
      highlights that the crystal packing has a crucial influence on the temperature
      range in which the SMM behavior is observed. In the case of the well-insulated
      Tb(III)-based derivative (2A), the SMM behavior is observed at higher
      temperatures and lower frequencies than for the one that presents close-packing
      between the molecules (2B). Comparisons are then possible only under an applied
      external magnetic field (0.2 T) with Delta = 27.5(6) and 21.0(5) K and tau0 =
      2.64(25) * 10(-9) and 1.76(20) * 10(-9) s for 2A and 2B, respectively. 

PMID- 23126264
TI  - The effect of unpredicted visual feedback on activation in the secondary
      somatosensory cortex during movement execution.
AB  - BACKGROUND: A mechanism that monitors the congruence between sensory inputs and
      motor outputs is necessary to control voluntary movement. The representation of
      limb position is constantly updated on the basis of somatosensory and visual
      information and efference copy from motor areas. However, the cortical mechanism
      underlying detection of limb position using somatosensory and visual information
      has not been elucidated. This study investigated the influence of visual feedback
      on information processing in somatosensory areas during movement execution using
      magnetoencephalography. We used an experimental condition in which the visual
      information was incongruent despite the motor execution and somatosensory
      feedback being congruent. Subjects performed self-paced bimanual movements of
      both thumbs, either symmetric or asymmetric, under normal visual and mirrored
      conditions. The mirror condition provided a visual feedback by showing a
      reflection of the subject's right hand in place of the left hand. Therefore, in
      the Asymmetric task of the Mirror condition, subjects saw symmetric movements
      despite performing asymmetric movements. RESULTS: Activation in the primary
      somatosensory area (SI) revealed inhibition of neural activity and that in the
      secondary somatosensory area (SII) showed enhancement with voluntary movement. In
      addition, the SII contralateral to the side of stimulation was significantly
      enhanced in the Asymmetric task of the Mirror condition, which provided non
      veridical visual feedback. CONCLUSIONS: These results suggested that visual
      information influenced the neuronal activity concerning sensorimotor interaction
      in the SII during motor execution. The SII contributes to the detection of
      unpredicted visual feedback of movement execution.

PMID- 23126265
TI  - Transcriptional and functional variation of NF-YC1 in genetically diverse
      accessions of Phaseolus vulgaris during the symbiotic association with Rhizobium
      etli.
AB  - Phaseolus vulgaris (common bean) is an agronomic important legume crop native to
      America, where two centres of genetic diversification (GD) are recognised, one in
      Mesoamerica and the other in the south Andes. Mesoamerican bean accessions have
      preferential and more efficient nodulation with Rhizobium etli strains carrying
      the allele nodC type-alpha, which is predominant in soils of Mesoamerica. It was
      previously demonstrated that the host nuclear factor NF-YC1, which is involved in
      nodule formation and rhizobial infection, contributes to this preferential
      selection and enhances nodulation in the domesticated accession NAG12 from
      Mesoamerica. Here, we show that both domesticated and wild Mesoamerican beans
      exhibit higher nodulation performance with a nodC type-alpha than with a nodC
      type-delta strain. Transcripts of NF-YC1 significantly increased in roots of
      these accessions 24 h post-inoculation (hpi) with the nodC type-alpha strain. On
      the other hand, accessions from the Andean GD centre formed a higher number of
      nodules with a strain carrying the nodC type-delta, which is predominant in
      Andean soils. However, NF-YC1 transcript levels did not exhibit significant
      changes in Andean accessions upon inoculation with the nodC type-delta strain, at
      least at 24 hpi. RNA interference (RNAi)-mediated gene silencing of NF-YC1 in the
      domesticated Andean accession Alubia showed that NF-YC1 or a closely related
      member of this family is required for nodule formation and bacterial infection,
      in agreement with observations in Mesoamerican common beans. Isolation and
      sequencing of the full-length ORF of NF-YC1 from Alubia revealed that it was
      identical to the sequence previously identified in the Mesoamerican accession
      NAG12. Interestingly, overexpression of NF-YC1 had a negative impact on nodule
      formation in the Alubia accession, independently of the R. etli lineage. Our
      findings suggest that transcriptional and functional variation of NF-YC1 occurs
      among genetically diverse bean accessions, which might positively or negatively
      contribute to the fine-tuning mechanisms that regulate nodule formation in the
      common bean-R. etli symbiosis.

PMID- 23126267
TI  - Structure and Bonding analysis of the cationic electrophilic phosphinidene
      complexes of iron, ruthenium, and osmium [(eta(5)-C5Me5)(CO)2M{PN(i)Pr2}]+,
      [(eta(5)-C5H5)(CO)2M{PNR2}]+ (R = Me, (i)Pr), and [(eta(5)-C5H5)(PMe3)2M{PNMe2}]+
      (M = Fe, Ru, Os).
AB  - Quantum-chemical DFT calculations for the electronic, molecular structure and M
      PNR(2) bonding analyses of the experimentally known cationic electrophilic
      phosphinidene complexes [(eta(5)-C(5)Me(5))(CO)(2)M{PN(i)Pr(2)}](+) and of the
      model complexes [(eta(5)-C(5)H(5))(CO)(2)M{PNR(2)}](+) (R = (i)Pr, Me) and
      [(eta(5)-C(5)H(5))(PMe(3))(2)M{PNMe(2)}](+) were carried out using BP86/TZ2P/ZORA
      level of theory. The calculated geometrical parameters of the studied complexes
      are in good agreement with the reported experimental values. The short M-P bond
      distances and calculated Pauling bond orders (range of 1.23-1.68), suggest the
      presence of M-P multiple bond characters. The Hirshfeld charge analysis shows
      that the overall charge flows from phosphinidene ligand to metal fragment. The M
      P sigma-bonding orbitals are well-occupied (>1.80e). The energy decomposition
      analysis revealed that the contribution of the electrostatic interaction
      DeltaE(elstat) is, in all studied complexes, significantly larger (55.2-62.6%)
      than the orbital interactions DeltaE(orb). The orbital interactions between metal
      and PNR(2) in [(eta(5)-C(5)H(5))(L)(2)M{PNR(2)}](+) arise mainly from M <- PNR(2)
      sigma-donation. The pi-bonding contribution (19-36%) is much smaller than the
      sigma-bonding. The interaction energies, as well as bond dissociation energies,
      depend on the auxiliary ligand framework around the metal and decrease in the
      order (eta(5)-C(5)H(5)) > (eta(5)-C(5)Me(5)) and CO > PMe(3). Upon substitution
      of R = (i)Pr with smaller group R = Me, the M-PNR(2) bond strength slightly
      decreases.

PMID- 23126266
TI  - Expression of oral secretory leukocyte protease inhibitor in HIV-infected
      subjects with long-term use of antiretroviral therapy.
AB  - BACKGROUND: The objectives of this study were to determine (i) the expression of
      oral secretory leukocyte protease inhibitor (SLPI) in HIV-infected subjects
      compared with non-HIV controls, (ii) the oral SLPI expression in HIV-infected
      subjects with antiretroviral therapy (ART) compared with those without ART, and
      (iii) factors associated with the expression of oral SLPI. METHODS: Oral tissues
      and samples of both un-stimulated and stimulated saliva were collected from HIV
      infected subjects with and without ART, and non-HIV individuals. The expression
      of SLPI mRNA in the tissue was determined by quantitative real-time PCR. Salivary
      SLPI protein was detected using ELISA. Chi-square test and logistic regression
      analysis were performed to determine the association between HIV/ART status and
      the expression of oral SLPI. RESULTS: One hundred and fifty-seven HIV-infected
      subjects were enrolled: 99 on ART (age range, 23-57 years; mean, 39 years), 58
      not on ART (age range, 20-59 years; mean, 34 years), and 50 non-HIV controls (age
      range, 19-59 years; mean, 36 years). The most common ART regimen was 2NRTIs +
      1NNRTI. The expression of oral SLPI in stimulated saliva was significantly
      decreased with HIV infection (P < 0.001). The expression was also significantly
      different with respect to ART use (P = 0.007). Smoking, CD4(+) cell count, and
      HIV viral load were the factors associated with the oral SLPI expression.
      CONCLUSION: The expression of oral SLPI is altered by HIV infection and use of
      ART. Thus, oral SLPI may be the useful biomarker to identify subjects at risk of
      infections and malignant transformation due to HIV infection and long-term ART.

PMID- 23126268
TI  - Expression of Orseolia oryzae nucleoside diphosphate kinase (OoNDPK) is enhanced
      in rice gall midge feeding on susceptible rice hosts and its over-expression
      leads to salt tolerance in Escherichia coli.
AB  - The Asian rice gall midge, Orseolia oryzae, is a major dipteran pest of rice,
      with many known biotypes. The present investigation was initiated to understand
      the molecular mechanisms of infestation for developing novel integrated pest
      management strategies. We isolated and characterized a gene, nucleoside
      diphosphate kinase (OoNDPK), from the rice gall midge, encoding a protein with
      169 amino acid residues and with a secretory signal sequence - an observation
      that assumes significance as salivary gland secretions have been implicated to
      play a major role in insect-plant interactions. Furthermore, up-regulation (> 18
      folds) of OoNDPK was observed in the salivary glands of maggots feeding on
      susceptible host in contrast to those feeding on resistant host. Phylogenetic
      analysis revealed similarity of OoNDPK with its dipteran orthologues.
      3DLigandSite analysis, of the predicted OoNDPK and its orthologues, revealed
      phenylalanine and tyrosine residues to be specifically present in NDPK proteins
      from the plant feeders. Results suggest secretion of OoNDPK into the host plant
      and its probable involvement in gall midge-rice interaction. Using the coleoptile
      cell elongation assay, we demonstrated that the recombinant OoNDPK is capable of
      causing elongation of rice coleoptile cells. Additionally, heterologous
      expression of OoNDPK in Escherichia coli increased the tolerance of these cells
      to salt (NaCl; up to 1 mM), hinting at the involvement of this gene in abiotic
      stress response as well.

PMID- 23126269
TI  - Molecular cloning and characterization of an endogenous digestive beta
      glucosidase from the midgut of the fungus-growing termite Macrotermes barneyi.
AB  - beta-glucosidase from the midgut of the fungus-growing termite Macrotermes
      barneyi was first cloned and characterized to gain a better understanding of
      cellulolytic systems in fungus-growing termites. beta-glucosidase activity was
      proven to present primarily in the midgut of M. barneyi and two beta-glucosidases
      were partially purified from the midgut. Based on the N-terminus sequence of one
      of the beta-glucosidases, a full-length cDNA fragment of 1708 bp was obtained.
      This sequence encodes a 493 amino acid protein belonging to glycoside hydrolase
      family 1. Quantitative real-time PCR analysis proved that the beta-glucosidase
      gene was primarily expressed in the midgut. beta-glucosidase was expressed
      heterologously and biochemically characterized. Results indicate that beta
      glucosidase is an endogenous, midgut-origin termite digestive enzyme. It may have
      applications in understanding the mechanism of lignocellulose degradation in
      fungus-growing termites.

PMID- 23126270
TI  - Associative learning mechanisms underpinning the transition from recreational
      drug use to addiction.
AB  - Learning theory proposes that drug seeking is a synthesis of multiple
      controllers. Whereas goal-directed drug seeking is determined by the anticipated
      incentive value of the drug, habitual drug seeking is elicited by stimuli that
      have formed a direct association with the response. Moreover, drug-paired stimuli
      can transfer control over separately trained drug seeking responses by retrieving
      an expectation of the drug's identity (specific transfer) or incentive value
      (general transfer). This review covers outcome devaluation and transfer of
      stimulus-control procedures in humans and animals, which isolate the differential
      governance of drug seeking by these four controllers following various degrees of
      contingent and noncontingent drug exposure. The neural mechanisms underpinning
      these four controllers are also reviewed. These studies suggest that although
      initial drug seeking is goal-directed, chronic drug exposure confers a
      progressive loss of control over action selection by specific outcome
      representations (impaired outcome devaluation and specific transfer), and a
      concomitant increase in control over action selection by antecedent stimuli
      (enhanced habit and general transfer). The prefrontal cortex and mediodorsal
      thalamus may play a role in this drug-induced transition to behavioral autonomy.

PMID- 23126271
TI  - Timing of administration of prophylactic antibiotics for caesarean section: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Prophylactic antibiotics reduce infectious morbidity from caesarean
      section. The timing of their administration, however, is a matter of controversy.
      OBJECTIVES: To examine maternal and neonatal infectious morbidity in women
      receiving preoperative prophylaxis compared with those receiving intraoperative
      administration. SEARCH STRATEGY: Medline, Embase, Current Controlled Trials and
      Cochrane Central were searched from their inception dates to December 2011.
      SELECTION CRITERIA: Randomised controlled trials of a single dose of any
      antibiotic comparing preoperative with intraoperative administration were
      selected. DATA COLLECTION AND ANALYSIS: Trial characteristics, outcomes and
      quality measures, based on the Cochrane tool for risk of bias, were independently
      extracted. The random effect model of DerSimonian and Laird to estimate relative
      risks (RRs) for maternal and neonatal outcomes was used. MAIN RESULTS: Six trials
      met the inclusion criteria, reporting on 2313 women and 2345 newborns.
      Preoperative administration was associated with a significant 41% reduction in
      the rate of endometritis compared with intraoperative administration (RR 0.59;
      95% confidence interval [95% CI] 0.37-0.94; I2 0%). In the preoperative group,
      there were nonsignificant reductions in the rates of wound infection (RR 0.71;
      95% CI 0.44-1.14; I2 0%), maternal febrile morbidity (RR 0.94; 95% CI 0.46-1.95;
      I2 0%), neonatal sepsis (RR 0.81; 95% CI 0.47-1.41; I2 0%), neonatal septic work
      up (RR 0.93; 95% CI 0.71-1.21; I2 0%) and neonatal intensive-care unit admission
      (RR 0.92; 95% CI 0.65-1.28; I2 0%). There were nonsignificant increases in the
      rates of maternal pyelonephritis (RR 1.09; 95% CI 0.49-2.43; I2 0%) and neonatal
      pneumonia (RR 3.36; 95% CI 0.55-20.47; I2 0%). CONCLUSIONS: Compared with
      intraoperative administration, preoperative antibiotics significantly reduce the
      rate of endometritis. The lack of neonatal adverse effects should be cautiously
      interpreted given the limited power of the trials to detect such effects.

PMID- 23126273
TI  - Pharmacokinetic evaluation of eszopiclone: clinical and therapeutic implications.
AB  - INTRODUCTION: Eszopiclone is the active S-enantiomer of R,S-zopiclone, and is a
      cyclopyrrolone hypnotic acting via the GABA-benzodiazepine receptor system.
      Nearly 6 million prescriptions for eszopiclone are written yearly in the United
      States. AREAS COVERED: This paper addresses the pharmacokinetic properties of
      eszopiclone and the extent to which the longer half-life of eszopiclone compared
      to other commonly used hypnotics (immediate-release zolpidem, modified-release
      zolpidem, triazolam, zaleplon) may translate into either improved efficacy in
      enhancing sleep maintenance, or increased probability of residual sedative or
      performance-impairing effects. EXPERT OPINION: Eszopiclone is metabolized mainly
      by Cytochrome P450-3A (CYP3A) isoforms. The mean half-life in healthy nonelderly
      individuals (6.1 h) is prolonged in the elderly, in patients with hepatic
      insufficiency, and by coadministration of CYP3A inhibitors. In clinical trials,
      eszopiclone consistently improves sleep maintenance relative to placebo, based on
      measures of shortened wake time after sleep onset, and prolonged total sleep
      time. However eszopiclone may also produce residual sedation and impairment of
      driving performance in the initial morning waking hours. A bitter or metallic
      taste is a common though non-serious adverse effect of eszopiclone. Overall,
      eszopiclone provides a therapeutic option for patients with sleep maintenance
      problems, though with accompanying potential for residual morning sedation, as
      well as a relatively high dollar cost of treatment.

PMID- 23126274
TI  - Detection of the GD2+/CD56+/CD45- immunophenotype by flow cytometry in
      cerebrospinal fluids from a patient with retinoblastoma.
AB  - Triple-color flow cytometry with a panel of antibodies comprising GD2, CD56, and
      CD45 was performed to analyze cerebrospinal fluids (CSF) from a patient with
      retinoblastoma who was suspicious of meningeal metastasis based on clinical
      presentation. Our results showed that the cells in CSF demonstrated the
      immunophenotype positive for GD2 and CD56 but negative for CD45 antigen, which
      suggested the presence of CSF metastasis of retinoblastoma. At the end of eight
      cycles of intrathecal chemotherapy, CSF specimen was analyzed with Flow cytometry
      immunophenotyping (FCI) again and the result showed no detectable malignant cells
      with the same immunophenotype. Our conclusion is that FCI can be a quick and
      reliable method for the diagnosis of CSF metastasis of retinoblastoma and the
      immunophenotype (GD2+, CD56+, and CD45-) can be used to recognize residual
      retinoblastoma cells in CSF.

PMID- 23126272
TI  - Ca(2+) sparks promote myogenic tone in retinal arterioles.
AB  - BACKGROUND AND PURPOSE: Ca(2+) imaging reveals subcellular Ca(2+) sparks and
      global Ca(2+) waves/oscillations in vascular smooth muscle. It is well
      established that Ca(2+) sparks can relax arteries, but we have previously
      reported that sparks can summate to generate Ca(2+) waves/oscillations in
      unpressurized retinal arterioles, leading to constriction. We have extended these
      studies to test the functional significance of Ca(2+) sparks in the generation of
      myogenic tone in pressurized arterioles. EXPERIMENTAL APPROACH: Isolated retinal
      arterioles (25-40 MUm external diameter) were pressurized to 70 mmHg, leading to
      active constriction. Ca(2+) signals were imaged from arteriolar smooth muscle in
      the same vessels using Fluo4 and confocal laser microscopy. KEY RESULTS: Tone
      development was associated with an increased frequency of Ca(2+) sparks and
      oscillations. Vasomotion was observed in 40% of arterioles and was associated
      with synchronization of Ca(2+) oscillations, quantifiable as an increased cross
      correlation coefficient. Inhibition of Ca(2+) sparks with ryanodine, tetracaine,
      cyclopiazonic acid or nimodipine, or following removal of extracellular Ca(2+) ,
      resulted in arteriolar relaxation. Cyclopiazonic acid-induced dilatation was
      associated with decreased Ca(2+) sparks and oscillations but with a sustained
      rise in the mean global cytoplasmic [Ca(2+) ] ([Ca(2+) ]c ), as measured using
      Fura2 and microfluorimetry. CONCLUSIONS AND IMPLICATIONS: This study provides
      direct evidence that Ca(2+) sparks can play an excitatory role in pressurized
      arterioles, promoting myogenic tone. This contrasts with the generally accepted
      model in which sparks promote relaxation of vascular smooth muscle. Changes in
      vessel tone in the presence of cyclopiazonic acid correlated more closely with
      changes in spark and oscillation frequency than global [Ca(2+) ]c , underlining
      the importance of frequency-modulated signalling in vascular smooth muscle.

PMID- 23126275
TI  - Perception of affective prosody in patients at an early stage of relapsing
      remitting multiple sclerosis.
AB  - Cognitive dysfunction is well known in patients suffering from multiple sclerosis
      (MS) and has been described for many years. Cognitive impairment, memory, and
      attention deficits seem to be features of advanced MS stages, whereas depression
      and emotional instability already occur in early stages of the disease. However,
      little is known about processing of affective prosody in patients in early stages
      of relapsing-remitting MS (RRMS). In this study, tests assessing attention,
      memory, and processing of affective prosody were administered to 25 adult
      patients with a diagnosis of RRMS at an early stage and to 25 healthy controls
      (HC). Early stages of the disease were defined as being diagnosed with RRMS in
      the last 2 years and having an Expanded Disability Status Scale (EDSS) of 2 or
      lower. Patients and HC were comparable in intelligence quotient (IQ), educational
      level, age, handedness, and gender. Patients with early stages of RRMS performed
      below the control group with respect to the subtests 'discrimination of affective
      prosody' and 'matching of affective prosody to facial expression' for the emotion
      'angry' of the 'Tubingen Affect Battery'. These deficits were not related to
      executive performance. Our findings suggest that emotional prosody comprehension
      is deficient in young patients with early stages of RRMS. Deficits in
      discriminating affective prosody early in the disease may make misunderstandings
      and poor communication more likely. This might negatively influence interpersonal
      relationships and quality of life in patients with RRMS.

PMID- 23126276
TI  - Effect of co-exposure to nickel and particulate matter on insulin resistance and
      mitochondrial dysfunction in a mouse model.
AB  - BACKGROUND: It has been well recognized that toxicity of fine ambient air
      particulate matter (PM(2.5)) may depend on its chemical constituents, including
      components such as soluble metals that may theoretically exert distinctive
      effects. We have recently demonstrated an important effect of PM(2.5) on
      metabolic function. Since transition metals, such as nickel (Ni), represent an
      important component of exposure in certain environments, and may significantly
      influence the toxicity of inhalational exposure, we investigated the effects of
      Ni as a variable component of ambient PM(2.5) exposure. METHODS: Male ApoE
      knockout mice were exposed to filtered air (FA), fine-sized nickel sulfate
      particles alone (Ni) at 0.44 MUg/m(3), concentrated ambient air PM(2.5) (CAPs) at
      a mean of 70 MUg/m(3), or CAPs+Ni in Tuxedo, NY, 6 hours/day, 5 days/week, for 3
      months. RESULTS: Exposure to Ni, irrespective of co-exposure to CAPs, resulted in
      body weight gain, while exposure to CAPs+Ni significantly enhanced fasting
      glucose and worsened insulin resistance measures (HOMA-IR), when compared with
      exposure to CAPs alone. CAPs+Ni exposure induced a significant decrease in
      phosphorylation of AMP-activated protein kinase (AMPK) alpha. Exposure to Ni or
      CAPs+Ni significantly induced microcirculatory dysfunction and increased
      monocytic cell infiltration into lung and adipose, and decreased uncoupling
      protein 1 expression at gene and protein levels and several brown adipocyte
      specific genes in adipose tissue. CONCLUSIONS: Ni exposure has effects on
      metabolic and inflammatory parameters that are comparable to that of CAPs.
      Additionally, Ni synergistically exacerbates CAPs-induced adverse effects on some
      of, but not all of, these parameters, that may be mediated via the AMPK signaling
      pathway. These findings have important implications for inhaled transition metal
      toxicity that may exert synergistic effects with other PM(2.5) components.

PMID- 23126278
TI  - Detection of acrolein-derived cyclic DNA adducts in human cells by monoclonal
      antibodies.
AB  - Acrolein (Acr) is a ubiquitous environmental pollutant found in cigarette smoke
      and automobile exhaust. It can also be produced endogenously by oxidation of
      polyunsaturated fatty acids. The Acr-derived 1,N(2)-propanodeoxyguanosine (Acr
      dG) adducts in DNA are mutagenic lesions that are potentially involved in human
      cancers. In this study, monoclonal antibodies were raised against Acr-dG adducts
      and characterized using ELISA. They showed strong reactivity and specificity
      toward Acr-dG, weaker reactivity toward crotonaldehyde- and trans-4-hydroxy-2
      nonenal-derived 1,N(2)-propanodeoxyguanosines, and weak or no reactivity toward
      1,N(6)-ethenodeoxyadenosine and 8-oxo-deoxyguanosine. Using these antibodies, we
      developed assays to detect Acr-dG in vivo: first, a simple and quick FACS-based
      assay for detecting these adducts directly in cells; second, a highly sensitive
      direct ELISA assay for measuring Acr-dG in cells and tissues using only 1 MUg of
      DNA without DNA digestion and sample enrichment; and third, a competitive ELISA
      for better quantitative measurement of Acr-dG levels in DNA samples. The assays
      were validated using Acr-treated HT29 cell DNA samples or calf thymus DNA, and
      the results were confirmed by LC-MS/MS-MRM. An immunohistochemical assay was also
      developed to detect and visualize Acr-dG in HT29 cells as well as in human oral
      cells. These antibody-based methods provide useful tools for the studies of Acr
      dG as a cancer biomarker and of the molecular mechanisms by which cells respond
      to Acr-dG as a ubiquitous DNA lesion.

PMID- 23126277
TI  - Population pharmacokinetics of abacavir in infants, toddlers and children.
AB  - AIMS: To characterize the pharmacokinetics of abacavir in infants, toddlers and
      children and to assess the influence of covariates on drug disposition across
      these populations. METHODS: Abacavir concentration data from three clinical
      studies in human immunodeficiency virus-infected children (n = 69) were used for
      model building. The children received either a weight-normalized dose of 16 mg
      kg(-1) day(-1) or the World Health Organization recommended dose based on weight
      bands. A population pharmacokinetic analysis was performed using nonlinear mixed
      effects modelling VI. The influence of age, gender, bodyweight and formulation
      was evaluated. The final model was selected according to graphical and
      statistical criteria. RESULTS: A two-compartmental model with first-order
      absorption and first-order elimination best described the pharmacokinetics of
      abacavir. Bodyweight was identified as significant covariate influencing the
      apparent oral clearance and volume of distribution. Predicted steady-state
      maximal plasma concentration and area under the concentration-time curve from 0
      to 12 h of the standard twice daily regimen were 2.5 mg l(-1) and 6.1 mg h l(-1)
      for toddlers and infants, and 3.6 mg l(-1) and 8.7 mg h l(-1) for children,
      respectively. Model-based predictions showed that equivalent systemic exposure
      was achieved after once and twice daily dosing regimens. There were no
      pharmacokinetic differences between the two formulations (tablet and solution).
      The model demonstrated good predictive performance for dosing prediction in
      individual patients and, as such, can be used to support therapeutic drug
      monitoring in conjunction with sparse sampling. CONCLUSIONS: The disposition of
      abacavir in children appears to be affected only by differences in size,
      irrespective of the patient's age. Maturation processes of abacavir metabolism in
      younger infants should be evaluated in further studies to demonstrate the
      potential impact of ontogeny.

PMID- 23126279
TI  - Autologous platelet-rich plasma promotes neurogenic differentiation of human
      adipose-derived stem cells in vitro.
AB  - Nervous system injury causes severe medical and social problems worldwide, and
      doctors have not found any ultimate solutions to it until now. The regenerative
      medicine using stem cells is a promising technology to conquer this challenge. In
      this study, we explored the influence of platelet-rich plasma (PRP) on neural
      differentiation of adipose-derived stem cells (ASCs). Human ASCs (hASCs) were
      harvested and isolated from lipoaspirates of liposuction operations. They were
      cultured to the third passage and characterized by specific cell markers and
      multilineage differentiation capacities. Autologous PRP was isolated and prepared
      from venous blood of the same patient underwent liposuction. The cultured hASCs
      were treated with either neural inductive conditioned medium plus 10% PRP
      (experimental group) or neural inductive conditioned medium alone (control
      group). The supplement of autologous PRP into culture medium obviously promoted
      proliferation of hASCs. After two weeks of neurogenic induction, the hASCs
      treated with PRP displayed higher level of neuron-specific enolase and membrane
      associated protein-2 compared with the control group. Gene expression level of
      growth associated protein-43 (GAP-43), neural cell adhesion molecule (NCAM), and
      synapsin 1 (SYN-1) in the PRP group was also higher than in the control group.
      These results indicate PRP is capable of promoting cell proliferation and
      neurogenic differentiation of hASCs in vitro. Addition of autologous PRP could
      facilitate the potential use of hASCs in nerve regeneration.

PMID- 23126281
TI  - Sonographic assessment of changes in diaphragmatic kinetics induced by
      inspiratory resistive loading.
AB  - BACKGROUND AND OBJECTIVE: Diaphragmatic breathing patterns under resistive
      loading remain poorly documented. To our knowledge, this is the first study
      assessing diaphragmatic motion under conditions of inspiratory resistive loading
      with the use of sonography. METHODS: We assessed diaphragmatic motion during
      inspiratory resistive loading in 40 healthy volunteers using M-mode sonography.
      In phase I of the study, sonography was performed during normal quiet breathing
      without respiratory loading. In phase II, sonography was performed after
      application of a nose clip and connection of the subjects to a pneumotachograph
      through a mouth piece. In phase III, the participants were assessed while
      subjected to inspiratory resistive loading of 50 cm H(2)O/L/s. RESULTS: Compared
      with baseline, the application of a mouth piece and nose clip induced a
      significant increase in diaphragmatic excursion (from 1.7 to 2.3 cm, P < 0.001)
      and a decrease in respiratory rate (from 13.4 to 12.2, P < 0.01). Inspiratory
      resistive loading induced a further decrease in respiratory rate (from 12.2 to
      8.0, P < 0.01) and a decrease in diaphragmatic velocity contraction (from 1.2 to
      0.8 cm/s, P < 0.01), and also an increase in tidal volume (from 795 to 904 mL, P
      < 0.01); diaphragmatic excursion, however, did not change significantly.
      CONCLUSIONS: Inspiratory resistive loading induced significant changes in
      diaphragmatic contraction pattern, which mainly consisted of decreased velocity
      of diaphragmatic displacement with no change in diaphragmatic excursion. Tidal
      volume, increased significantly; the increase in tidal volume, along with the
      unchanged diaphragmatic excursion, provides sonographic evidence of increased
      recruitment of extradiaphragmatic muscles under inspiratory resistive loading.

PMID- 23126280
TI  - Regulation of adipogenesis by cytoskeleton remodelling is facilitated by
      acetyltransferase MEC-17-dependent acetylation of alpha-tubulin.
AB  - Cytoskeleton remodelling is a prerequisite step for the morphological transition
      from preadipocytes to mature adipocytes. Although microtubules play a pivotal
      role in organizing cellular structure, regulation of microtubule dynamics during
      adipogenesis remains unclear. In the present paper we show that acetylation of
      alpha-tubulin is up-regulated during adipogenesis, and adipocyte development is
      dependent on alpha-tubulin acetylation, as expression of an acetylation-resistant
      alpha-tubulin mutant significantly inhibits adipogenesis. Moreover, acetylation
      of alpha-tubulin is under the control of the acetyltransferase MEC-17 and
      deacetylases SIRT2 (Sirtuin 2) and HDAC6 (histone deacetylase 6). Adipocyte
      development is inhibited in MEC-17-knockdown cells, but enhanced in MEC-17
      overexpressing cells. Finally, we show that katanin, a microtubule-severing
      protein with enhanced activity on acetylated alpha-tubulin, is actively involved
      in adipogenesis. We propose that co-ordinated up-regulation of alpha-tubulin
      acetylation initiates cytoskeleton remodelling by promoting alpha-tubulin
      severing by katanin which, in turn, allows expansion of lipid droplets and
      accelerates the morphological transition toward mature adipocytes.

PMID- 23126283
TI  - Synthesis of the peptaibol framework of the anticancer agent culicinin D:
      stereochemical assignment of the AHMOD moiety.
AB  - The postulated structure of the potent anticancer peptaibol culicinin D has been
      synthesized using Fmoc-based solid-phase peptide synthesis (SPPS). Comparison of
      the (1)H NMR data for the reported structure of culicinin D with the data
      obtained for the two synthetic polypeptides epimeric at C-6 in the AHMOD unit
      established the C-6 stereochemistry of the AHMOD residue in the natural product
      to be (R).

PMID- 23126282
TI  - Antiangiogenesis and antioxidant activity of ethanol extracts of Pithecellobium
      jiringa.
AB  - BACKGROUND: Angiogenesis plays a critical role in embryonic development and
      various physiological processes. However, excessive angiogenesis is associated
      with several pathological conditions including cancer. Pithecellobium jiringa
      (Jack) Prain is a traditional medicinal plant from the family Leguminosae. It is
      native to the Southeast Asia, where it has been used traditionally for treatment
      of various ailments such as hypertension and diabetes. The present work is aimed
      to study antioxidant and antiangiogenesis activities of P. jiringa ethanol
      extracts. METHODS: P. jiringa fruit rinds were extracted with ethanol and 50%
      ethanol. The antioxidant property was analysed using, 1,1-diphenyl-2-picryl
      hydrazyl free radical scavenging assay. Phytochemical analysis was performed
      using thin layer chromatography and colorimetric methods. Then, cell growth
      inhibition was studied against a panel of human cell lines by MTT test. In vitro
      inhibition of angiogenesis was studied by the following assays: isolated rat
      aortic rings cell viability, colony formation, endothelial cell migration,
      endothelial tube formation on matrigel, and expression of vascular endothelial
      growth factor by endothelial cells. In vivo antiangiogenesis effect was studied
      by utilising fertilised chick embryos assay. The results were statistically
      analysed by analysis of variance. RESULTS: Ethanolic and 50% hydro-ethanolic
      extracts showed relatively high concentration of total phenolics associated with
      potent antioxidant activity. The rat aortic rings study conducted showed potent
      inhibition of the microvessels outgrowth with IC50s 5.27 +/- 0.81 MUg/ml
      (ethanolic) and 4.45 +/- 0.63 MUg/ml (50% hydro-ethanolic). Both extracts
      arrested the growth of human endothelial cells via down-regulation of VEGF
      expression, leading to inhibition of other angiogenesis cascades including
      migration of endothelial cells, and formation of capillary network on matrigel
      matrix. The extracts also inhibited the neovascularisation of chick embryo
      chorioallantoic membrane. CONCLUSIONS: P. jiringa extracts inhibit angiogenesis
      by blocking the VEGF expression thus inhibiting endothelial cells proliferation,
      migration and differentiation most likely due to presence of the antioxidant
      phenolics.

PMID- 23126284
TI  - Rib butterfly fractures as a possible indicator of blast trauma.
AB  - Forensic anthropologists have become increasingly involved in the interpretation
      of skeletal trauma caused by exploding ordnance. This study examines the cause
      and significance of butterfly fractures observed in a recent study investigating
      skeletal blast trauma by Christensen et al. Fractured ribs resulting from blast
      events carried out in the original study were re-examined revealing that rib
      butterfly fractures with the tensile indicator on the visceral surface were
      present in 100% of viable pig specimens. Additionally, manual fracture testing
      was performed on 46 pig ribs to simulate the bending force believed to have been
      sustained in the original blast events. Fracture testing resulted in 93% of
      specimens presenting butterfly fractures with the tensile indicator on the
      visceral surface. This fracture pattern differs significantly from that normally
      observed in association with other types of trauma events and may aid forensic
      anthropologists and other investigators in the identification and interpretation
      of blast events.

PMID- 23126252
TI  - Effects of dalcetrapib in patients with a recent acute coronary syndrome.
AB  - BACKGROUND: In observational analyses, higher levels of high-density lipoprotein
      (HDL) cholesterol have been associated with a lower risk of coronary heart
      disease events. However, whether raising HDL cholesterol levels therapeutically
      reduces cardiovascular risk remains uncertain. Inhibition of cholesteryl ester
      transfer protein (CETP) raises HDL cholesterol levels and might therefore improve
      cardiovascular outcomes. METHODS: We randomly assigned 15,871 patients who had
      had a recent acute coronary syndrome to receive the CETP inhibitor dalcetrapib,
      at a dose of 600 mg daily, or placebo, in addition to the best available evidence
      based care. The primary efficacy end point was a composite of death from coronary
      heart disease, nonfatal myocardial infarction, ischemic stroke, unstable angina,
      or cardiac arrest with resuscitation. RESULTS: At the time of randomization, the
      mean HDL cholesterol level was 42 mg per deciliter (1.1 mmol per liter), and the
      mean low-density lipoprotein (LDL) cholesterol level was 76 mg per deciliter (2.0
      mmol per liter). Over the course of the trial, HDL cholesterol levels increased
      from baseline by 4 to 11% in the placebo group and by 31 to 40% in the
      dalcetrapib group. Dalcetrapib had a minimal effect on LDL cholesterol levels.
      Patients were followed for a median of 31 months. At a prespecified interim
      analysis that included 1135 primary end-point events (71% of the projected total
      number), the independent data and safety monitoring board recommended termination
      of the trial for futility. As compared with placebo, dalcetrapib did not alter
      the risk of the primary end point (cumulative event rate, 8.0% and 8.3%,
      respectively; hazard ratio with dalcetrapib, 1.04; 95% confidence interval, 0.93
      to 1.16; P=0.52) and did not have a significant effect on any component of the
      primary end point or total mortality. The median C-reactive protein level was 0.2
      mg per liter higher and the mean systolic blood pressure was 0.6 mm Hg higher
      with dalcetrapib as compared with placebo (P<0.001 for both comparisons).
      CONCLUSIONS: In patients who had had a recent acute coronary syndrome,
      dalcetrapib increased HDL cholesterol levels but did not reduce the risk of
      recurrent cardiovascular events. (Funded by F. Hoffmann-La Roche; dal-OUTCOMES
      ClinicalTrials.gov number, NCT00658515.).

PMID- 23126285
TI  - Discrete nanomolecular polyhedral borane scaffold supporting multiple
      gadolinium(III) complexes as a high performance MRI contrast agent.
AB  - An icosahedral closo-B(12)(2-) scaffold supports 12 copies of Gd(3+)-chelate held
      in close proximity with each other by suitable linkers which employ azide-alkyne
      click chemistry. This design is the first member of a new class of polyfunctional
      MRI contrast agents carrying a high payload of Gd(3+)-chelate in a sterically
      constrained configuration. The resulting contrast agent shows higher relaxivity
      values at high magnetic fields. MRI contrast agents currently in use are not as
      effective in this regard, presumably due to a lack of steric constraint of
      gadolinium centers and lower water exchange rates. In vivo MRI studies in mice
      show excellent contrast enhancement even at one-seventh of the safe clinical dose
      (0.04 mmol Gd/kg) for up to a 1 h exposure.

PMID- 23126286
TI  - The role of the tolerance-fecundity trade-off in maintaining intraspecific seed
      trait variation in a widespread dimorphic herb.
AB  - Coexistence of species with different seed sizes is a long-standing issue in
      community ecology, and a trade-off between fecundity and stress tolerance has
      been proposed to explain co-occurrence in heterogeneous environments. Here we
      tested an intraspecific extension of this model: whether such trade-off also
      explains seed trait variation among populations of widespread plants under stress
      gradients. We collected seeds from 14 populations of Plantago coronopus along the
      Atlantic coast in North Africa and Europe. This herb presents seed dimorphism,
      producing large basal seeds with a mucilaginous coat that facilitates water
      absorption (more stress tolerant), and small apical seeds without coats (less
      stress tolerant). We analysed variation among populations in number, size and
      mucilage production of basal and apical seeds, and searched for relationships
      between local environment and plant size. Populations under higher stress (higher
      temperature, lower precipitation, lower soil organic matter) had fewer seeds per
      fruit, higher predominance of basal relative to apical seeds, and larger basal
      seeds with thicker mucilaginous coats. These results strongly suggest a trade-off
      between tolerance and fecundity at the fruit level underpins variation in seed
      traits among P. coronopus populations. However, seed production per plant showed
      the opposite pattern to seed production per fruit, and seemed related to plant
      size and other life-cycle components, as an additional strategy to cope with
      environmental variation across the range. The tolerance-fecundity model may
      constitute, under stress gradients, a broader ecological framework to explain
      trait variation than the classical seed size-number compromise, although several
      fecundity levels and traits should be considered to understand the diverse
      strategies of widespread plants to maximise fitness in each set of local
      conditions. 

PMID- 23126289
TI  - Impact of photosensitivity disorders on the life quality of children.
AB  - BACKGROUND/PURPOSE: Abnormal cutaneous sensitivity to the ultraviolet and/or
      visible radiation in sunlight characterizes photosensitivity disorders. Little is
      known regarding their impact in childhood. Our objective was to characterize
      childhood photosensitivity disorders presenting to a photoinvestigation unit,
      evaluating their impact on quality of life (QoL). METHODS: Photoinvestigation
      records of children attending from 2000 to 2007 were evaluated for diagnosis,
      clinical, demographic and phototest parameters. These children were subsequently
      contacted during summertime to evaluate the impact of photosensitivity on QoL,
      utilizing the children's dermatology life quality index (CDLQI). RESULTS: 83
      children underwent photoinvestigation; 62 (74.7%) were diagnosed photosensitive
      (mean age 8.6 years, range 2-16; 33 female), with abnormal phototest findings in
      35 children. 38/55 questionnaires (69.1%) were returned. Mean (+/- standard
      deviation) CDLQI score (all diagnoses) was 10.2 +/- 7.3 with very high scores in
      xeroderma pigmentosum (20.7 +/- 5.7; n = 3) and actinic prurigo (18.2 +/- 7.1; n
      = 6) and moderate scores in photoaggravated eczema (7.9 +/- 4.2; n = 8) and
      polymorphic light eruption (6.2 +/- 4.4 n = 18). CDLQI correlated with number of
      months affected per year (r = 0.595, P = 0.001). CONCLUSION: Photosensitivity
      disorders have a substantial impact, ranging from moderate to extremely large, on
      QoL in childhood, and the psychological consequences should be considered in
      their management.

PMID- 23126287
TI  - Transcranial magnetic stimulation with a half-sine wave pulse elicits direction
      specific effects in human motor cortex.
AB  - BACKGROUND: Transcranial magnetic stimulation (TMS) commonly uses so-called
      monophasic pulses where the initial rapidly changing current flow is followed by
      a critically dampened return current. It has been shown that a monophasic TMS
      pulse preferentially excites different cortical circuits in the human motor hand
      area (M1-HAND), if the induced tissue current has a posterior-to-anterior (PA) or
      anterior-to-posterior (AP) direction. Here we tested whether similar direction
      specific effects could be elicited in M1-HAND using TMS pulses with a half-sine
      wave configuration. RESULTS: In 10 young participants, we applied half-sine
      pulses to the right M1-HAND which elicited PA or AP currents with respect to the
      orientation of the central sulcus.Measurements of the motor evoked potential
      (MEP) revealed that PA half-sine stimulation resulted in lower resting motor
      threshold (RMT) than AP stimulation. When stimulus intensity (SI) was gradually
      increased as percentage of maximal stimulator output, the stimulus-response curve
      (SRC) of MEP amplitude showed a leftward shift for PA as opposed to AP half-sine
      stimulation. Further, MEP latencies were approximately 1 ms shorter for PA
      relative to AP half-sine stimulation across the entire SI range tested. When
      adjusting SI to the respective RMT of PA and AP stimulation, the direction
      specific differences in MEP latencies persisted, while the gain function of MEP
      amplitudes was comparable for PA and AP stimulation. CONCLUSIONS: Using half-sine
      pulse configuration, single-pulse TMS elicits consistent direction-specific
      effects in M1-HAND that are similar to TMS with monophasic pulses. The longer MEP
      latency for AP half-sine stimulation suggests that PA and AP half-sine
      stimulation preferentially activates different sets of cortical neurons that are
      involved in the generation of different corticospinal descending volleys.

PMID- 23126290
TI  - Single administration of lesion-limited high-dose (TURBO) ultraviolet B using the
      excimer laser: clinical clearing in association with apoptosis of epidermal and
      dermal T cell subsets in psoriasis.
AB  - BACKGROUND/PURPOSE: Development of effective therapy for psoriasis is confounded
      by numerous factors contributing to disease pathogenesis, including pathogenic
      immunocytes which appear to drive epidermal keratinocyte hyperproliferation. Our
      objective was to study clinical and biomarker effects of a single dose of TURBO
      laser UVB (308 nm) applied directly to psoriatic plaques. METHODS: Eighteen
      patients with chronic plaque psoriasis received a single dose of 10 minimal
      erythema dose (MED) UVB and were followed for 8 weeks. Keratome and punch
      biopsies were assessed for T cell depletion and apoptosis following a single 308
      nm dose of UVB. RESULTS: Patients demonstrated clinical improvement as indicated
      by decreased global Psoriasis Area and Severity Index scores and reduced numbers
      of pathogenic memory/effector T cells infiltrating lesional epidermis and dermis.
      Consistent with apoptosis induction, caspase activation increased in lesional T
      cells after treatment. CONCLUSION: We conclude that a single 10 MED dose of TURBO
      UVB is effective at reducing the severity and extent of psoriatic lesions. We
      hypothesize that the reason a single treatment is sufficient to clear a psoriatic
      plaque is that the 10 MED dose is able to deliver sufficient photons to a
      microanatomic area of the lesion where susceptible pathogenic T cell mechanisms
      are operative.

PMID- 23126291
TI  - Antiphotoaging effect of chitooligosaccharides on human dermal fibroblasts.
AB  - BACKGROUND/PURPOSE: In the present study, the effect of 3-5 kDa
      chitooligosaccharide (COS) on homeostasis between the expression of collagen
      degrading matrix metalloproteinases (MMPs) and collagen synthesis was
      investigated using ultraviolet (UV)-A irradiated dermal fibroblasts. METHODS: UV
      protection imparted by 3-5 kDa COS was measured by examining the UV absorption
      spectrum. Collagenase MMP secretion was examined using an enzyme-linked
      immunosorbent assay. The levels of collagenases and collagen synthetic markers
      were determined by employing the reverse transcriptase-polymerase chain reaction
      and Western blot analysis. RESULTS: The 3-5 kDa COS not only absorbed UV-A and UV
      B light but also inhibited collagenase (MMP-1, MMP-8, and MMP-13) and gelatinase
      (MMP-2 and MMP-9) MMP expression. The suppression of MMP expression was found to
      be due to an increase in expression of the tissue inhibitors of MMP (TIMP)-1 and
      TIMP-2. Treatment with 3-5 kDa COS enhanced collagen synthetic markers such as
      procollagen, type I, III, and IV collagens in UV-A-irradiated dermal fibroblasts.
      Furthermore, the effects of 3-5 kDa COS on collagen degradation and collagen
      synthesis in UV-A irradiated dermal fibroblasts were regulated via the inhibition
      of activating protein-1 (AP-1) signaling. CONCLUSION: Our results suggest that 3
      5 kDa COS can be used to develop as topical applications for antiphotoaging
      cosmeceuticals as it enhances collagen synthesis.

PMID- 23126292
TI  - The effect of ultraviolet radiation from a novel portable fluorescent lamp on
      serum 25-hydroxyvitamin D3 levels in healthy adults with Fitzpatrick skin types
      II and III.
AB  - BACKGROUND/PURPOSE: Ultraviolet (UV) B irradiation may provide a safe and
      effective method to treat vitamin D deficiency. The objective of this study was
      to assess the effectiveness of a novel Sperti D/UV-Fluorescent lamp in converting
      7-dehydrocholesterol (7-DHC) to previtamin D(3) in vitro and in raising serum 25
      hydroxyvitamin D(3) [25(OH)D(3) ] in healthy adults. METHODS: The lamp was
      assessed in vitro using a 7-DHC solution and a human skin sample. In a
      prospective cohort study, five healthy adults with skin types II and III were
      exposed to a 0.75 minimal erythemal dose of UV radiation over ~ 9% of body
      surface area three times a week for 4 weeks. The main outcomes were percentage of
      conversion from 7-DHC to previtamin D(3) in vitro and changes in serum 25(OH)D(3)
      after irradiation in vivo. RESULTS: A dose response between UV irradiation time
      and conversion of 7-DHC to previtamin D(3) was seen in the 7-DHC solution and
      surgically obtained human skin. The subjects had a significant increase in mean
      25(OH)D(3) from 18.4 +/- 8.2 to 27.3 +/- 7.6 ng/ml (P < 0.001) after 4 weeks of
      irradiation. No adverse events occurred. CONCLUSION: The Sperti D/UV-Fluorescent
      lamp is effective in converting 7-DHC to previtamin D(3) in vitro and in raising
      serum 25(OH)D(3) in healthy adults.

PMID- 23126293
TI  - Photoprotective effects of Bifidobacterium breve supplementation against skin
      damage induced by ultraviolet irradiation in hairless mice.
AB  - BACKGROUND: Probiotics have been considered to affect not only the gut but also
      the skin. This study aimed at examining whether oral administration of live
      Bifidobacterium breve strain Yakult (BBY), a typical probiotic, could exert
      photoprotective effects in hairless mouse skin. METHODS: BBY cell suspensions and
      fermented milk containing BBY (BBYM) were orally administered to hairless mice
      for 9 and 14 days, respectively. Mice were irradiated with ultraviolet (UV) light
      daily for the last four consecutive days. Twenty-four hours after the final
      irradiation, skin elasticity, appearance, elastase activity and interleukin (IL)
      1beta levels were evaluated in the dorsal skin. RESULTS: BBY and BBYM
      significantly prevented UV-induced deleterious changes in skin elasticity and
      appearance. BBY suppressed the increases in both elastase activity and IL-1beta
      levels in the skin. There was a significant negative correlation between elastase
      activity and the ratio of elastic recovery to total deformation and a significant
      positive correlation between elastase activity and the area ratio of furrows,
      independent of UV irradiation or BBY administration. CONCLUSION: Our findings
      suggest that oral administration of probiotic BBY has the potential to prevent UV
      induced skin damage, supporting the hypothesis that probiotics are beneficial not
      only to the intestine but also to the skin.

PMID- 23126294
TI  - Normal minimal erythema dose responses in patients with suspected
      photosensitivity disorders.
AB  - PURPOSE: Our study identified the most common diagnoses in patients with a
      history of photosensitivity or with a photodistributed eruption and normal
      minimal erythema dose (MED) responses. METHODS: We retrospectively reviewed the
      diagnoses and phototest results of 319 patients who were phototested at the New
      York University Photomedicine Section of the Charles C. Harris Skin and Cancer
      Pavilion from 1993 to 2009. Patients were phototested if they had a history of
      photosensitivity or had an eruption with a distribution that suggested
      photosensitivity. RESULTS: The majority of patients with normal MEDs were
      diagnosed with polymorphous light eruption, followed by contact or photocontact
      dermatitis, photodistributed dermatitis not otherwise specified (idiopathic),
      solar urticaria and photoexacerbated atopic dermatitis. DISCUSSION: The clinical
      history of photosensitivity and physical findings remain as important metrics in
      the diagnosis of patients with photodistributed dermatoses and normal MEDs.

PMID- 23126295
TI  - Phloroglucinol protects human keratinocytes from ultraviolet B radiation by
      attenuating oxidative stress.
AB  - BACKGROUND: Ultraviolet B generates reactive oxygen species by interacting with
      water in irradiated skin tissues and cells in turn causes lipid peroxidation,
      protein modification and further DNA damage. PURPOSE: This study examined the
      cytoprotective effects of phloroglucinol (1,3,5-trihydroxybenzene) on ultraviolet
      B-irradiated cultured human keratinocytes. METHODS: The human keratinocyte cell
      line HaCaT cells were treated with 10 MUM of phloroglucinol. After 1 h, the cells
      were irradiated with ultraviolet B light at 30 mJ/cm(2) and incubated at 37
      degrees C. RESULTS: Phloroglucinol scavenged both the superoxide anion and
      hydroxyl radical in a cell-free system and ultraviolet B-induced intracellular
      reactive oxygen species. Phloroglucinol reduced ultraviolet B-generated lipid
      peroxidation, protein modification and DNA strand breaks. The enzymatic effects
      of phloroglucinol restored cellular glutathione levels, superoxide dismutase and
      catalase activities, which were impaired by ultraviolet B radiation. CONCLUSION:
      Phloroglucinol provides the protective effects in human keratinocyte cell line
      exposed to ultraviolet B radiation, suggesting that phloroglucinol can be used as
      a photoprotective agent.

PMID- 23126296
TI  - Low-irradiance red LED traffic lamps as light source in PDT for actinic
      keratoses.
AB  - LED light sources for photodynamic therapy have become increasingly popular due
      to their narrow emission spectra that accurately match the absorption spectrum of
      porphyrins. Photodynamic therapy at low fluence rates has been shown to be as
      effective as high output irradiation for treatment of non-melanoma skin cancers.
      Fifteen patients with multiple non-hypertrophic actinic keratoses covering the
      scalp and the face were treated with aminolaevulinic acid photodynamic therapy
      using ordinary red LED traffic lamps as light source. All 15 patients improved
      clinically after one photodynamic therapy session. Only two patients required a
      second session to obtain satisfactory remission. Pain was minimal during these
      sessions. Red LED traffic lights constitute a simple alternative to far more
      complicated and expensive PDT light sources.

PMID- 23126297
TI  - Photoprotection counseling of non-white ethno-racial groups: a survey of the
      practice of expert dermatologists.
AB  - The morbidity of skin cancer in non-white, ethno-racial populations is well
      established, yet no specific guidelines exist addressing the manner in which this
      population should be counseled on photoexposure. We conducted a 20-item survey to
      assess the behavior of specialized dermatologists when providing photoprotection
      recommendations to non-white, ethno-racial patients as well as the perceived
      relevance of counseling for this group. Our study demonstrated that key opinion
      leaders within the fields of photodermatology and ethnic dermatology believe that
      photoprotection counseling is beneficial for ethno-racial minorities. Based on
      these preliminary data and other recently published reports, the development of
      photoprotection guidelines specific to non-white, ethno-racial groups may be
      warranted.

PMID- 23126298
TI  - Perception of xeroderma pigmentosum support group members of xeroderma
      pigmentosum lifestyle impact.
AB  - Xeroderma pigmentosum (XP) is a genetic condition, which can cause an extreme
      sensitivity to sunlight and an increased risk of skin cancer due to errors in DNA
      repair. An online survey was administered to a convenience sample of participants
      who were members of an online support group for XP patients and their families to
      determine common symptoms and quality of life. The Dermatologic Life Quality
      Index (DLQI) or the Children's Dermatologic Life Quality Index (CDLQI) was used
      depending on patient age. A total of four patients and two parents of young
      patients completed our survey. Quality of life as measured through the DLQI and
      CDLQI was moderately affected.

PMID- 23126299
TI  - Optogenetic reporters.
AB  - The discovery of naturally evolved fluorescent proteins and their subsequent
      tuning by protein engineering provided the basis for a large family of
      genetically encoded biosensors that report a variety of physicochemical processes
      occurring in living tissue. These optogenetic reporters are powerful tools for
      live-cell microscopy and quantitative analysis at the subcellular level. In this
      review, we present an overview of the transduction mechanisms that have been
      exploited for engineering these genetically encoded reporters. Finally, we
      discuss current and future efforts towards the combined use of various
      optogenetic actuators and reporters for simultaneously controlling and imaging
      the physiology of cells and tissues.

PMID- 23126300
TI  - Theoretical study on the reaction mechanisms of CH3O- with O2(X3Sigma(g)-) and
      O2(a1Delta(g)).
AB  - The detailed potential energy surfaces (PESs) of poorly understood  ion-molecule
      reactions of CH(3)O(-) with O(2)(X(3)Sigma(g)(-)) and O(2)(a(1)Delta(g)) are
      accounted for by the density functional theory and ab initio of QCISD and CCSD(T)
      (single-point) theoretical levels with 6-311++G(d,p) and 6-311++G(3df,2pd) basis
      sets for the first time. For the reaction of CH(3)O(-) with O(2)(X(3)Sigma(g)(-))
      ((3)R), it is shown that a hydrogen-bonded complex (3)1 is initially formed on
      the triplet PES, which is 1.8 kcal/mol above reactants (3)R at the CCSD(T)//QCISD
      level, from which all the products P(1)-P(8) can be generated. As to the reaction
      of CH(3)O(-) with O(2)(a(1)Delta(g)) ((1)R), it is found that the two
      energetically low-lying complexes of (1)1(-31.5 kcal/mol) and (1)2(-24.1
      kcal/mol) are initiated on the singlet PES. Starting from them, a total of seven
      products may be possible, that is, besides P(1), P(2), P(3), P(4), and P(8),
      which are the same as on the triplet PES, there exist also another two products,
      P(9) and P(10). For both reactions, taking the thermodynamics and kinetics into
      consideration, the hydride-transfer species P(1)(CH(2)O + HO(2)(-)) should be the
      most favorable product followed by P(8)(e + CH(2)O + HO(2)), which is a secondary
      product of electron-detachment from P(1), and the generation of endothermic
      P(7)(17.7 kcal/mol) for the reaction of CH(3)O(-) with O(2)(X(3)Sigma(g)(-)) is
      also possible at high temperature, whereas the remaining products are negligible.
      The measured branching ratio of products for CH(3)O(-) with O(2)(X(3)Sigma(g)(-))
      by Midey et al. is 0.85:0.15 for P(1) and P(8), and that of CH(3)O(-) with
      O(2)(a(1)Delta(g)) is 0.52:0.48 with more P(8), which can be rationalized by our
      theoretical results that P(8) on the triplet PES is 4.9 kcal/mol above (3)R,
      whereas both P(1) and P(8) on the singlet PES are very low-lying at 45.6 and 25.2
      kcal/mol below (1)R energetically. The measured total reaction rate constant of
      CH(3)O(-) with O(2)(a(1)Delta(g)) is k = 6.9 * 10(-10) cm(3) s(-1) at 300 K,
      which is larger than that of k = 1.1 * 10(-12) cm(3) s(-1) for the reaction of
      CH(3)O(-) with O(2)(X(3)Sigma(g)(-)). This is understandable because both P(1)
      and P(8) on the singlet PES can be generated barrierlessly, whereas to give all
      the products on the triplet PES has to pass the barrier of (3)1(1.8 kcal/mol) at
      the CCSD(T)//QCISD level. It is expected that the present theoretical study may
      be helpful for understanding the reaction mechanisms related to CH(3)O(-) and
      even CH(3)S(-).

PMID- 23126303
TI  - Poster presentations in the virtual world.
AB  - This column describes a creative virtual-world approach used by the American
      Nurses Association Center for Continuing Education and Professional Development
      to provide an additional venue for continuing nursing education within a large
      conference format. Hurdles that were overcome in developing a virtual world of
      poster presentations included determining how to award contact hours, how to
      secure funding, how to separate sponsorship from the integrity of the learning
      activity, and how to manage submissions and content.

PMID- 23126304
TI  - Palliative care in a community hospital: educating nurses to embrace this new
      initiative.
AB  - Palliative care, often mistaken for hospice care, improves patients' quality of
      life via symptom management of life-limiting illnesses. A community hospital
      began a palliative care team. Along with Nursing Education, this team educated a
      group of nurses to implement treatment modalities and offered ongoing education
      to prepare nurses to become certified in palliative and hospice nursing.

PMID- 23126305
TI  - The Learner-Centered Syllabus.
AB  - The Learner-Centered Syllabus (LCS) is a carefully constructed all-inclusive
      course guide. Using a LCS encourages and empowers students to take an active role
      in the learning process.

PMID- 23126307
TI  - Aspirin in the prevention of pre-eclampsia in high-risk women: a randomised
      placebo-controlled PREDO Trial and a meta-analysis of randomised trials.
AB  - OBJECTIVE: To study the effect of aspirin in the prevention of pre-eclampsia in
      high-risk women. DESIGN: Randomised, double-blinded, placebo-controlled trial.
      SETTING: Maternity clinics in ten Finnish hospitals participating in the PREDO
      Project. SAMPLE: A total of 152 women with risk factors for pre-eclampsia and
      abnormal uterine artery Doppler velocimetry. METHODS: Participants were
      randomised to start either aspirin 100 mg/day or placebo at 12 + 0 to 13 + 6
      weeks + days of gestation. Because of the limited power of this trial, we also
      conducted a meta-analysis of randomised controlled trials that included data on
      346 women with abnormal uterine artery Doppler flow velocimetry, and aspirin 50
      150 mg/day started at or before 16( ) weeks of gestation. MAIN OUTCOME MEASURE:
      Pre-eclampsia, gestational hypertension and birthweight standard deviation (SD)
      score. Outcome measures for the meta-analysis were pre-eclampsia, severe pre
      eclampsia, preterm (diagnosed <37 + 0 weeks of gestation) and term pre-eclampsia.
      RESULTS: From the 152 randomised women, 121 were included in the final analysis.
      Low-dose aspirin did not reduce the rate of pre-eclampsia (relative risk [RR]
      0.7, 95% CI 0.3-1.7); gestational hypertension (RR 1.6, 95% CI 0.6-4.2); early
      onset pre-eclampsia (diagnosed <34 + 0 weeks of gestation) (RR 0.2, 95% CI 0.03
      2.1); or severe pre-eclampsia (RR 0.4, 95% CI 0.1-1.3); and the results were not
      statistically significant in an intention-to-treat analysis. However, our meta
      analysis, including the current data, suggested that low-dose aspirin initiated
      before 16 weeks of gestation reduces the risk of pre-eclampsia (RR 0.6, 95% CI
      0.4-0.8) and severe pre-eclampsia (RR 0.3, 95% CI 0.1-0.7). CONCLUSIONS: Our
      trial showed no statistically significant effect of aspirin in preventing pre
      eclampsia in high-risk women. However, our meta-analysis suggested that aspirin
      may reduce the incidence of pre-eclampsia.

PMID- 23126310
TI  - Chinese teachers' use of humour in coping with stress.
AB  - The purpose of this study was to examine the mentality of Chinese teachers
      regarding their use of humour in coping with stress. Specifically, the study
      investigated their frequency of use of humour in coping with stress as compared
      to other coping styles and their perceptions about the relationship of humour
      with other coping styles. Data were collected from a sample of 789 Chinese
      teachers holding teaching posts at local Hong Kong secondary schools. Based on
      responses made to the COPE questionnaire, there was evidence that Chinese
      teachers had a lower frequency of use of humour as compared to other coping
      styles. As suggested by the results of a factor analysis, there was a perception
      among Chinese teachers that the use of humour was related more closely to
      escaping and/or avoidance as coping strategies, but more differentiable from
      problem-focused/task-oriented and emotional/social coping. It is interesting to
      find that the results of our study echoed those of a previous crosscultural
      comparison between Chinese and Canadian university students, in which the Chinese
      university students reported less use of humour in coping with stress than did
      their Canadian counterparts. These results have provided some empirical support
      for the notion that "humor has been traditionally given little respect in Chinese
      culture mainly due to the Confucian emphasis on keeping proper manners in social
      interactions" (Yue, 2010, p. 403). As teachers in Chinese societies are regarded
      as persons who are full of wisdom and capable of problem-solving, it is expected
      that they should act as role models to their students. These social expectations
      on Chinese teachers could further mould their perceptions on the use of humour in
      coping with stress. 

PMID- 23126308
TI  - Deferasirox (ICL670A) effectively inhibits oesophageal cancer growth in vitro and
      in vivo.
AB  - BACKGROUND AND PURPOSE: Growing evidence implicates iron in the aetiology of
      gastrointestinal cancer. Furthermore, studies demonstrate that iron chelators
      possess potent anti-tumour activity, although whether iron chelators show
      activity against oesophageal cancer is not known. EXPERIMENTAL APPROACH: The
      effect of the iron chelators, deferoxamine (DFO) and deferasirox, on cellular
      iron metabolism, viability and proliferation was assessed in two oesophageal
      adenocarcinoma cell lines, OE33 and OE19, and the squamous oesophageal cell line,
      OE21. A murine xenograft model was employed to assess the effect of deferasirox
      on oesophageal tumour burden. The ability of chelators to overcome
      chemoresistance and to enhance the efficacy of standard chemotherapeutic agents
      (cisplatin, fluorouracil and epirubicin) was also assessed. KEY RESULTS:
      Deferasirox and DFO effectively inhibited cellular iron acquisition and promoted
      intracellular iron mobilization. The resulting reduction in cellular iron levels
      was reflected by increased transferrin receptor 1 expression and reduced cellular
      viability and proliferation. Treating oesophageal tumour cell lines with an iron
      chelator in addition to a standard chemotherapeutic agent resulted in a reduction
      in cellular viability and proliferation compared with the chemotherapeutic agent
      alone. Both DFO and deferasirox were able to overcome cisplatin resistance.
      Furthermore, in human xenograft models, deferasirox was able to significantly
      suppress tumour growth, which was associated with decreased tumour iron levels.
      CONCLUSIONS AND IMPLICATIONS: The clinically established iron chelators, DFO and
      deferasirox, effectively deplete iron from oesophageal tumour cells, resulting in
      growth suppression. These data provide a platform for assessing the utility of
      these chelators in the treatment of oesophageal cancer patients.

PMID- 23126309
TI  - Ion mobility-mass spectrometry analysis of serum N-linked glycans from esophageal
      adenocarcinoma phenotypes.
AB  - Three disease phenotypes, Barrett's esophagus (BE), high-grade dysplasia (HGD),
      esophageal adenocarcinoma (EAC), and a set of normal control (NC) serum samples
      are examined using a combination of ion mobility spectrometry (IMS), mass
      spectrometry (MS), and principal component analysis (PCA) techniques. Samples
      from a total of 136 individuals were examined, including 7 characterized as BE,
      12 as HGD, 56 as EAC, and 61 as NC. In typical data sets, it was possible to
      assign ~20 to 30 glycan ions based on MS measurements. Ion mobility distributions
      for these ions show multiple features. In some cases, such as the [S1H5N4+3Na]3+
      and [S1F1H5N4+3Na]3+ glycan ions, the ratio of intensities of high-mobility
      features to low-mobility features vary significantly for different groups. The
      degree to which such variations in mobility profiles can be used to distinguish
      phenotypes is evaluated for 11 N-linked glycan ions. An outlier analysis on each
      sample class followed by an unsupervised PCA using a genetic algorithm for
      pattern recognition reveals that EAC samples are separated from NC samples based
      on 46 features originating from the 11-glycan composite IMS distribution.

PMID- 23126311
TI  - Alteration of affective Theory of Mind in amnestic mild cognitive impairment.
AB  - The concept of amnestic mild cognitive impairment (aMCI) concerns a population of
      older individuals at high risk of developing probable Alzheimer's disease (AD).
      Impairments of the cognitive component of Theory of Mind (ToM), that is the
      inference about other people's beliefs, have been well documented in AD; on the
      contrary, controversial findings have been reported on the affective component of
      ToM (inference about other's feelings), a process mainly based on medial portions
      of the prefrontal cortex. The current study aimed at evaluating the affective
      component of ToM in aMCI subjects. Twenty aMCI subjects and 20 age-matched
      healthy controls (HC) underwent a standard neuropsychological assessment and the
      assessment of affective ToM with the full 36-item version of reading the mind in
      the eyes (RME). Although aMCI subjects had formal impaired performances only in
      memory tasks, HC outperformed aMCI subjects in several cognitive tasks, including
      also the RME (mean RME scores 21.7 +/- 3.0 vs. 17.0 +/- 3.8%; 60.3% of correct
      answers vs. 47.2%). The lower RME performance of aMCI patients provides the first
      empirical evidence that aMCI may be associated with difficulties in tasks of
      affective ToM, in accordance with recent findings of early difficulties of aMCI
      patients in other processes that are mainly dependent on the medial prefrontal
      cortex, such as reversal learning and decision making under ambiguity. Findings
      of the current study need further empirical confirmation in larger samples of
      aMCI patients and also the investigation of other MCI subtypes is needed.

PMID- 23126313
TI  - Outcome following secondary autogenous bone grafting before and after canine
      eruption in patients with unilateral cleft lip and palate.
AB  - OBJECTIVE: To determine whether the long axis and eruption of the cleft-adjacent
      canine affect postoperative outcomes in secondary autogenous bone grafting
      (SABG). DESIGN: Retrospective longitudinal study. SETTING: Multidisciplinary long
      term follow-up at Kagoshima University Hospital. SUBJECTS AND METHODS: Twenty
      five patients with complete unilateral cleft lip and palate (11 male, 14 female)
      were compared between unerupted and erupted groups for canine developmental
      stage, canine angle, and vertical height at bone grafting at 1 year and more than
      4 years after SABG. The interalveolar septal heights at 1 and more than 4 years
      were evaluated by orthopantomograms. RESULTS: All patients in both groups
      accomplished dental rehabilitation with orthodontic treatment alone without
      prosthetic appliances. Although the rate of an acceptable bone bridge tended to
      be lower in the unerupted group (62.5%) than in the erupted group (88.8%), the
      difference was not significant (P = .158). The canine angle at bone grafting was
      significantly different between acceptable (69.2 degrees  +/- 12.2 degrees ) and
      poor cases (77.3 degrees  +/- 6.2 degrees ) at more than 4 years in the unerupted
      group (P = .049). The acceptable bone bridge rate might reflect mechanical stress
      added by natural eruption and orthodontic force. CONCLUSIONS: We suggest that
      SABG should be planned in accordance with the canine angle, crown and root
      development, the eruption position of the cleft-adjacent canine, and the timing
      of added mechanical stress in the alveolar cleft, considering the bone formation
      in the alveolar cleft.

PMID- 23126312
TI  - Patient directed self management of pain (PaDSMaP) compared to treatment as usual
      following total knee replacement: study protocol for a randomized controlled
      trial.
AB  - BACKGROUND: In 2009, 665 patients underwent total knee replacements (TKRs) at the
      Norfolk and Norwich University Hospitals NHS Foundation Trust (NNUH),
      representing nearly 1% of the national total. Pain control following the
      operation can be poor, and this can cause poor mobilization and potential long
      term adverse events. Although high levels of pain are not associated with patient
      dissatisfaction, brief periods of pain may lead to neuronal remodeling and
      sensitization. Patient controlled oral analgesia (PCOA) may improve pain relief;
      however, the evidence to date has been inconclusive. Patient directed self
      management of pain (PaDSMaP) is a single center randomized controlled trial,
      which aims to establish if patient self-medication improves, or is equivalent to,
      treatment as usual and to create an educational package to allow implementation
      elsewhere. METHODS/DESIGN: Patients eligible for a TKR will be recruited and
      randomized in the outpatient clinic. All patients will undergo their operations
      according to normal clinical practice but will be randomized into two groups.
      Once oral medication has commenced, one group will have pain relief administered
      by nursing staff in the usual way (treatment as usual; TAU), whilst the second
      group will self manage their pain medication (patient directed self management of
      pain; PaDSMaP). Those recruited for self-medication will undergo a training
      program to teach the use of oral analgesics according to the World Health
      Organization (WHO) pain cascade and how to complete the study documentation. The
      primary endpoint of the trial is the visual analogue scale (VAS) pain score at 3
      days or discharge, whichever is sooner. The follow-up time is 6 weeks with a
      planned trial period of 3 years. The secondary objectives are satisfaction with
      the management of patient pain post-operatively whilst an inpatient after primary
      TKR; overall pain levels and pain on mobilization; satisfaction with pain
      management information provided; global outcomes, such as quality of life (QOL)
      and activities of daily living (ADLs); time to mobilization and whether time to
      mobilization is associated with frequency of adverse events, improvements in QOL,
      ADLs and pain at 6 weeks after the operation; incidence of adverse events;
      quantity and type of pain medications used whilst an inpatient; the acceptability
      of PaDSMaP and/or TAU protocols for patients and the healthcare professionals
      involved in their care; to investigate the health-related costs associated with a
      PaDSMaP system; and to estimate the cost-effectiveness of PaDSMaP compared to
      TAU. TRIAL REGISTRATION: Current Controlled Trials ISRCTN: 10868989.

PMID- 23126314
TI  - Patterns of tooth agenesis in patients with crouzon or apert syndrome.
AB  - PURPOSE: Dental agenesis is the most common anomaly of dental development and can
      be a component of a congenital syndrome. The purpose of this study was to
      evaluate the prevalence of agenesis and to describe patterns of tooth agenesis in
      patients with Crouzon or Apert syndrome compared with nonsyndromic controls.
      PATIENTS AND METHODS: Longitudinal records of 67 patients with Crouzon syndrome
      (n = 39) or Apert syndrome (n = 28) from the Erasmus Medical Centre were
      examined. Syndromic patients were compared with patients in a nonsyndromic
      control group (n = 284). RESULTS: Prevalence of tooth agenesis in patients with
      Crouzon syndrome (35.9%) and patients with Apert syndrome (46.4%) was
      significantly higher than the prevalence in control subjects (27.5%) (P < .005).
      In all groups third molars were the most likely to be agenetic. Tooth agenesis
      excluding third molars was significantly higher in syndromic patients than in
      control subjects (P < .001). Bilateral agenesis of mandibular second premolars
      occurred significantly more often in patients with Crouzon and Apert syndrome
      than in control subjects (P < .001). CONCLUSIONS: Tooth agenesis is more
      prevalent in patients with Crouzon or Apert syndrome than in control subjects.
      Tooth agenesis and mandibular symmetrical patterns of second premolar agenesis
      are more prevalent in syndromic patients.

PMID- 23126316
TI  - Evaluation of the effectiveness of diode laser on pain and edema in individuals
      with cleft lip and palate submitted to secondary bone graft.
AB  - OBJECTIVE : To clinically evaluate the effects of diode laser, Gallium-Aluminum
      Arsenide laser (GaAlAs), on the pain and edema after secondary alveolar bone
      graft. DESIGN : Case-control, double-blind study. Setting : Institutional
      tertiary referral hospital. Participants : The sample was composed of 60
      individuals with complete unilateral cleft lip and palate, of both genders, aged
      9 to 15 years, submitted to secondary alveolar bone graft. MAIN OUTCOME MEASURES
      : The individuals were divided into an experimental group (patients irradiated
      with diode laser GaAlAs, energy density of 4 J/cm(2), power of 100 mW, and
      wavelength in the infrared spectrum, for 10 seconds per point on 10 points,
      adding up to a dose of 40 J/cm(2)) and a placebo group (simulated laser
      application for 60 seconds per point, also on 10 points). Applications were made
      on the receptor site immediately postoperatively and after 24 and 48 hours. The
      pain and edema were assessed preoperatively and at each application. RESULTS :
      The two groups presented increase in pain and edema in 24 and 48 hours. No
      statistically significant difference was found between groups. CONCLUSIONS :
      According to the present methodology, the use of low-level laser to control the
      pain and edema in the postoperative period of secondary alveolar bone graft was
      not effective.

PMID- 23126317
TI  - Tinnitus pitch, masking, and the effectiveness of hearing aids for tinnitus
      therapy.
AB  - OBJECTIVE: To assess the benefits of hearing aids on tinnitus according to the
      tinnitus reaction questionnaire (TRQ; Wilson et al, 1991), to verify whether the
      degree of masking provided by the hearing aid influenced the TRQ score, to
      examine whether the matched tinnitus pitch predicted the effectiveness of hearing
      aids in masking tinnitus, and to determine whether prescription of high-frequency
      amplification might be desirable in tinnitus management when tinnitus pitch is
      high. DESIGN AND STUDY SAMPLE: A retrospective evaluation of the clinical
      outcomes of 70 tinnitus patients fitted with hearing aids was undertaken. The
      primary outcome measure was the TRQ, with a secondary subjective measure of
      tinnitus masking. RESULTS: Participants who achieved masking with their hearing
      aids had greater reduction in TRQ scores. Masking was more likely to be achieved
      when participants had good low-frequency hearing and tinnitus pitch fell into the
      frequency range of the hearing aids. CONCLUSIONS: The results support the use of
      hearing aids for tinnitus management, and suggest that masking may be a
      significant contributor to hearing aid success, implying that high-frequency
      amplification may be effective in high-pitch tinnitus.

PMID- 23126318
TI  - Etoricoxib  and the treatment of ankylosing spondylitis.
AB  - INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAIDs) are first-line
      therapies in the management of patients with ankylosing spondylitis. This chronic
      inflammatory skeletal disorder, a subtype of spondyloarthritis, is characterized
      by inflammatory back pain and affects young adults causing important suffering
      and disability. Long-term use of conventional NSAIDs is associated with a risk of
      gastrointestinal complications. Etoricoxib is a specific cyclooxygenase 2
      inhibitor with strong anti-inflammatory effects and a favorable pharmacokinetic
      profile for the management of inflammatory disorders. The drug has been
      associated with reduced severe gastrointestinal adverse events. However, the
      cardiovascular safety of cyclooxygenase 2 inhibitors has been debated. AREAS
      COVERED: This review discusses etoricoxib in the treatment of ankylosing
      spondylitis. Literature searches were performed in PubMed, Web of Science, and
      the Cochrane library based on the terms "etoricoxib" and "ankylosing spondylitis"
      or "spondyloarthritis" as well as "safety" and "side-effects." EXPERT OPINION:
      Etoricoxib is useful in the first-line management of ankylosing spondylitis
      patients. Its anti-inflammatory effects and relative protection against severe
      gastrointestinal side effects should be balanced with negative effects on the
      cardiovascular system and an overall subjective tolerance not better than that of
      conventional NSAIDs. Whether etoricoxib will also become a mainstay in the
      prevention of structural damage in ankylosing spondylitis is not yet clear.

PMID- 23126320
TI  - Neuropathic pain, depressive symptoms, and C-reactive protein in sciatica
      patients.
AB  - There is evidence that neuropathic pain component in low back pain (LBP) patients
      is associated with higher ratings of comorbidities such as depression and anxiety
      disorders. In line with current findings, the purpose of this clinical study is
      to examine a hypothesis regarding a relationship of neuropathic pain component,
      depression, and other psychopathological symptoms in a specific group of LBP
      patients with sciatica pain. With respect to findings that depression is related
      to inflammatory changes, and inflammatory mediators may play a role in
      neuropathic pain generation, we have assessed also serum C-reactive protein
      (CRP). Results of the present study show that increased neuropathic pain
      component in sciatica patients is associated with elevated levels of depression,
      anxiety, alexithymia, and serum CRP levels. In conclusion, results of this study
      indicate that CRP levels in sciatica patients are closely associated with
      neuropathic pain.

PMID- 23126321
TI  - Base-catalyzed efficient tandem [3 + 3] and [3 + 2 + 1] annulation-aerobic
      oxidative benzannulations.
AB  - An efficient synthesis of substituted benzenes via a base-catalyzed [3 + 3]
      aerobic oxidative aromatization of alpha,beta-unsaturated carbonyl compounds with
      dimethyl glutaconate was reported. All the reactions were carried out under mild,
      metal-free conditions to afford the products in high to excellent yields with
      molecular oxygen as the sole oxidant and water as the sole byproduct.
      Furthermore, a more convenient tandem [3 + 2 + 1] aerobic oxidative aromatization
      reaction was developed through the in situ generation of the alpha,beta
      unsaturated carbonyl compounds from aldehydes and ketones.

PMID- 23126319
TI  - Antifungal agents and therapy for infants and children with invasive fungal
      infections: a pharmacological perspective.
AB  - Invasive fungal infections, although relatively rare, are life-threatening
      diseases in premature infants and immunocompromised children. While many advances
      have been made in antifungal therapeutics in the last two decades, knowledge of
      the pharmacokinetics and pharmacodynamics of antifungal agents for infants and
      children remains incomplete. This review summarizes the pharmacology and clinical
      utility of currently available antifungal agents and discusses the opportunities
      and challenges for future research.

PMID- 23126323
TI  - 3-D PSF fitting for fluorescence microscopy: implementation and localization
      application.
AB  - Localization microscopy relies on computationally efficient Gaussian
      approximations of the point spread function for the calculation of fluorophore
      positions. Theoretical predictions show that under specific experimental
      conditions, localization accuracy is significantly improved when the localization
      is performed using a more realistic model. Here, we show how this can be achieved
      by considering three-dimensional (3-D) point spread function models for the wide
      field microscope. We introduce a least-squares point spread function fitting
      framework that utilizes the Gibson and Lanni model and propose a computationally
      efficient way for evaluating its derivative functions. We demonstrate the
      usefulness of the proposed approach with algorithms for particle localization and
      defocus estimation, both implemented as plugins for ImageJ.

PMID- 23126322
TI  - The dynamic action of SecA during the initiation of protein translocation.
AB  - The motor ATPase SecA drives protein secretion through the bacterial Sec complex.
      The PPXD (pre-protein cross-linking domain) of the enzyme has been observed in
      different positions, effectively opening and closing a clamp for the polypeptide
      substrate. We set out to explore the implicated dynamic role of the PPXD in
      protein translocation by examining the effects of its immobilization, either in
      the position occupied in SecA alone with the clamp held open or when in complex
      with SecYEG with the clamp closed. We show that the conformational change from
      the former to the latter is necessary for high-affinity association with SecYEG
      and a corresponding activation of ATPase activity, presumably due to the PPXD
      contacting the NBDs (nucleotide-binding domains). In either state, the
      immobilization prevents pre-protein transport. However, when the PPXD was
      attached to an alternative position in the associated SecYEG complex, with the
      clamp closed, the transport capability was preserved. Therefore large-scale
      conformational changes of this domain are required for the initiation process,
      but not for translocation itself. The results allow us to refine a model for
      protein translocation, in which the mobility of the PPXD facilitates the transfer
      of pre-protein from SecA to SecYEG.

PMID- 23126324
TI  - Practical capability and cost effectiveness of a DNA pool-based genome-wide
      association study using BovineSNP50 array in a cattle population.
AB  - Genome-wide association mapping for complex traits in cattle populations is a
      powerful, but expensive, selection tool. The DNA pooling technique can
      potentially reduce the cost of genome-wide association studies. However, in DNA
      pooling design, the additional variance generated by pooling-specific errors must
      be taken into account. Therefore, this study aimed to investigate factors such
      as: (i) the accuracy of allele frequency estimation; (ii) the magnitude of errors
      in pooling construction and in the array; and (iii) the effect of the number of
      replicate arrays on P-values estimated by a genome-wide association study.
      Results showed that the Illumina correction method is the most effective method
      to correct the allele frequency estimation; pooling errors, especially array
      variance, should be taken into account in DNA pooling design; and the risk of a
      type I error can be reduced by using at least two replicate arrays. These results
      indicate the practical capability and cost-effectiveness of pool-based genome
      wide association studies using the BovineSNP50 array in a cattle population.

PMID- 23126325
TI  - McrA gene and 16S rRNA gene in the phylogenetic analysis of methanogens in the
      rumen of faunated and unfaunated cattle.
AB  - The influence of rumen protozoa on the composition of rumen methanogens was
      studied by using seven growing Holstein cattle divided into two groups: four
      faunated and three unfaunated. 16S ribosomal RNA gene (rDNA) and methyl coenzyme
      M reductase (MCR) alpha subunit (mcrA) gene clonal libraries were constructed.
      The results of each analysis showed that Methanobacteriales was dominant in the
      rumen of both groups. By mcrA gene analysis, 22.1% of unfaunated clones were
      classified into unfaunated group 1, which was not detected from faunated cattle.
      The 16S rRNA gene analysis showed that the number of operational taxonomic units
      was higher in unfaunated than faunated cattle, suggesting the diversity of
      methanogens tended to be higher by the removal of protozoa. The results of the
      LIBSHUFF program indicated that the 16S rRNA gene and mcrA gene clone libraries
      for the faunated group differed from those for the unfaunated group (P = 0.001).
      It was suggested that the presence of protozoa strongly affected the composition
      of rumen methanogens.

PMID- 23126326
TI  - Effects of adding food by-products mainly including noodle waste to total mixed
      ration silage on fermentation quality, feed intake, digestibility, nitrogen
      utilization and ruminal fermentation in wethers.
AB  - Four wethers were used in a 4 * 4 Latin square design experiment to evaluate the
      applicability of two types of total mixed ration (TMR) silage with food by
      products. Four food by-products (i.e., potato waste, soy sauce cake, soybean curd
      residue and noodle waste) were obtained and mixed with commercial concentrate
      (CC) as TMR silage. The two types of TMR silage, T1 and T2, each contained CC, in
      addition to all by-products for T1 (TRE1), and soy sauce cake and noodle waste
      for T2 (TRE2) on a dry matter (DM) basis. The silage was well-fermented with low
      pH values and high lactic acid concentration. As the experimental treatments, T1,
      T2 and CC (CTL) were fed with a basal diet. The result showed that the
      digestibility of DM and organic matter (OM) were higher for T1 than for CC (P <
      0.05), while crude protein digestibility was not significantly different among
      T1, T2 and CC. The retained nitrogen was not affected by inclusion of food by
      products. Ruminal pH in TRE1 and TRE2 immediately decreased compared to that in
      CTL. The study suggested that the two types of TMR silage, including food by
      products, might be used as a substitute for commercial concentrate.

PMID- 23126327
TI  - Nitrogen balance during compensatory growth when changing the levels of dietary
      lysine from deficiency to sufficiency in growing pigs.
AB  - Two experiments were conducted to elucidate the nitrogen (N) balance of pigs
      exhibiting compensatory growth when changing the dietary lysine levels from
      deficiency to sufficiency. Experiment 1 elucidated whether pigs exhibited
      compensatory growth with dietary lysine sufficiency. Twenty 6-week-old males were
      assigned to one of two treatments: control and LC (lysine and control). Control
      pigs were fed a control diet throughout the 24-day experimental period, whereas
      LC pigs were fed a low lysine diet until day 21 of the experiment, followed by
      the control diet until the end of experiment. The dietary lysine sufficiency
      treatment induced an 80% increase in the growth rate of LC pigs (P < 0.05).
      Experiment 2 focused on the N balance of pigs that exhibited compensatory growth
      with dietary lysine sufficiency. Eighteen 6-week-old males were assigned to one
      of three treatments: control, LC, and LL (low lysine). LL pigs were fed a low
      lysine diet throughout the 24-day experimental period. Pigs that exhibited
      compensatory growth with dietary lysine sufficiency tended to retain a higher
      amount of N than control pigs (P = 0.10). These finding suggest that the
      compensatory growth induced in pigs by dietary lysine sufficiency was partly
      attributable to a higher level of N retention.

PMID- 23126328
TI  - Relationships between muscle growth potential, intramuscular fat content and
      different indicators of muscle fibre types in young Charolais bulls.
AB  - Genetic selection in favor of muscle growth at the expense of fat should affect
      characteristics of muscles, and therefore beef quality. This study was conducted
      with two extreme groups of six animals selected among 64 Charolais young bulls
      ranked according to their genetic potential for muscle growth. Muscle
      characteristics were assessed in Rectus abdominis (RA, slow oxidative) and
      Semitendinosus (ST, fast glycolytic) muscles. Intramuscular fat content and
      proportions of myosin heavy chains I (slow) and IIA (fast oxido-glycolytic) and
      certain indicators of oxidative metabolism (activities of citrate synthase (CS),
      isocitrate dehydrogenase and cytochrome-c oxidase (COX); expression of H-fatty
      acid binding protein (FABP)) were higher in RA than in ST muscle. Genetic
      selection for muscle growth reduced intramuscular fat content and the activities
      of some oxidative metabolism indicators (namely CS, COX only). The positive
      correlation between muscle triacylglycerol content and A-FABP messenger RNA level
      (a marker of adipocyte differentiation) (r = 0.53, P < 0.05) suggests that A-FABP
      may be a good marker of the ability of bovines to deposit intramuscular fat. In
      conclusion, the metabolic muscle characteristics which respond to the selection
      process in favor of muscle growth clearly differ from the muscle characteristics
      which allow muscle types to be differentiated.

PMID- 23126329
TI  - Calf training for loading onto vehicle at weaning.
AB  - The aim of this study is to examine whether calf training for loading at the
      weaning period improves later loading. Five calves were allocated to the trained
      group and the control group, respectively. Calves in the trained group were
      loaded onto a livestock trailer for 5 successive days at weaning. Trainers led or
      hauled the calves by rope only. When loading was completed, trainers fed calves
      with sugar cubes as rewards. Calves in the control group were weaned without any
      treatment. Five weeks after weaning, tests were carried out under similar
      conditions as the trained group. Loading efficiency, physical effort on the
      handler and handling stress on calves between groups were compared. Trained
      calves were loaded significantly faster than control calves. Trained calves
      balked less during loading than control calves. Heart rates of handlers after
      loading were significantly lower in the trained group than in the control group;
      however, salivary amylase activity and cortisol concentration was not different
      between groups. Physical effort and stress on handlers would be almost the same
      in both groups. Heart rate, plasma cortisol, NEFA and CPK of calves were
      significantly increased only in the control group after loading. These results
      show calf training improves loading efficiency and reduces stress on calves.

PMID- 23126330
TI  - Synthetic models for the active site of the [FeFe]-hydrogenase: catalytic proton
      reduction and the structure of the doubly protonated intermediate.
AB  - This report compares biomimetic hydrogen evolution reaction catalysts with and
      without the amine cofactor (adt(NH)): Fe(2)(adt(NH))(CO)(2)(dppv)(2) (1(NH)) and
      Fe(2)(pdt)(CO)(2)(dppv)(2) (2) [(adt(NH))(2-) = HN(CH(2)S)(2)(2-), pdt(2-) = 1,3
      (CH(2))(3)S(2)(2-), and dppv = cis-C(2)H(2)(PPh(2))(2)]. These compounds are
      spectroscopically, structurally, and stereodynamically very similar but exhibit
      very different catalytic properties. Protonation of 1(NH) and 2 gives three
      isomeric hydrides each, beginning with the kinetically favored terminal hydride,
      which converts sequentially to sym and unsym isomers of the bridging hydrides. In
      the case of 1(NH), the corresponding ammonium hydrides are also observed. In the
      case of the terminal amine hydride [t-H1(NH)]BF(4), the ammonium/amine hydride
      equilibrium is sensitive to counteranions and solvent. The species [t
      H1(NH(2))](BF(4))(2) represents the first example of a crystallographically
      characterized terminal hydride produced by protonation. The NH---HFe distance of
      1.88(7) A indicates dihydrogen-bonding. The bridging hydrides [MU-H1(NH)](+) and
      [MU-H2](+) reduce near -1.8 V, about 150 mV more negative than the reductions of
      the terminal hydride [t-H1(NH)](+) and [t-H2](+) at -1.65 V. Reductions of the
      amine hydrides [t-H1(NH)](+) and [t-H1(NH(2))](2+) are irreversible. For the pdt
      analogue, the [t-H2](+/0) couple is unaffected by weak acids (pK(a)(MeCN) = 15.3)
      but exhibits catalysis with HBF(4).Et(2)O, albeit with a turnover frequency (TOF)
      around 4 s(-1) and an overpotential greater than 1 V. The voltammetry of [t
      H1(NH)](+) is strongly affected by relatively weak acids and proceeds at 5000 s(
      1) with an overpotential of 0.7 V. The ammonium hydride [t-H1(NH(2))](2+) is a
      faster catalyst, with an estimated TOF of 58 000 s(-1) and an overpotential of
      0.5 V.

PMID- 23126331
TI  - Mating in the pseudogamic apomictic Anemopaegma acutifolium DC: another case of
      pseudo-self-compatibility in Bignoniaceae?
AB  - Self-compatibility in apomictic pseudogamic species is considered fundamental to
      assure reproduction by seeds in extreme situations, making apomictic species more
      advantageous than sexual ones in these scenarios. Anemopaegma acutifolium is a
      polyploidy, apomictic sporophytic species with no endosperm development in ovules
      of unpollinated pistils, which indicates obligate pseudogamy. Thus, the aim of
      the present work is to study the breeding system and post-pollination events to
      test if there is similar pseudogamous development irrespective of pollination
      treatment. We analysed fruit and seed set obtained in controlled experimental
      pollinations, as well as embryo number per seed, and the progress of ovule
      penetration, fertilisation and early endosperm development between self- and
      cross-pollinated pistils. We found that the species is self-fertile and that
      spontaneous selfing fruit set is also possible, although emasculated flowers
      never form fruits. Selfed pistils were as efficient as crossed ones for all
      parameters analysed, except for a delay in endosperm development observed in the
      former that may be an effect of the late-acting self-incompatibility. Therefore,
      the avoidance of selfed pistil abortion seems to be promoted by the presence of
      adventitious embryos and a normal endosperm. We conclude that A. acutifolium
      shows apomixis-related pseudo-self-compatibility, as in other self-fertile
      apomictic species of Bignoniaceae, which confer reproductive assurance and
      increases fruit-set and persistence ability in fast-changing tropical habitats. 

PMID- 23126332
TI  - What do medical students think about their quality of life? A qualitative study.
AB  - BACKGROUND: Medical education can affect medical students' physical and mental
      health as well as their quality of life. The aim of this study was to assess
      medical students' perceptions of their quality of life and its relationship with
      medical education. METHODS: First- to sixth-year students from six Brazilian
      medical schools were interviewed using focus groups to explore what medical
      student's lives are like, factors related to increases and decreases of their
      quality of life during medical school, and how they deal with the difficulties in
      their training. RESULTS: Students reported a variety of difficulties and crises
      during medical school. Factors that were reported to decrease their quality of
      life included competition, unprepared teachers, excessive activities, and medical
      school schedules that demanded exclusive dedication. Contact with pain, death and
      suffering and harsh social realities influence their quality of life, as well as
      frustrations with the program and insecurity regarding their professional future.
      The scarcity of time for studying, leisure activities, relationships, and rest
      was considered the main factor of influence. Among factors that increase quality
      of life are good teachers, classes with good didactic approaches, active learning
      methodologies, contact with patients, and efficient time management. Students
      also reported that meaningful relationships with family members, friends, or
      teachers increase their quality of life. CONCLUSION: Quality of teachers,
      curricula, healthy lifestyles related to eating habits, sleep, and physical
      activity modify medical students' quality of life. Lack of time due to medical
      school obligations was a major impact factor. Students affirm their quality of
      life is influenced by their medical school experiences, but they also reframe
      their difficulties, herein represented by their poor quality of life, understood
      as necessary and inherent to the process of becoming doctors.

PMID- 23126334
TI  - Stabilization of hypophosphite in the binding pocket of a dinuclear macrocyclic
      complex: synthesis, structure, and properties of [Ni(2)L(MU-O(2)PH(2))]BPh(4) (L
      = N(6)S(2) donor ligand).
AB  - The dinickel(II) complex [Ni2L(ClO4)]ClO4 (1), where L(2-) represents a 24
      membered macrocyclic hexaamine-dithiophenolate ligand, reacts with [nBu4N]H2PO2
      to form the hypophosphito-bridged complex [Ni2L(MU-O2PH2)](+), which can be
      isolated as an air-stable perchlorate [Ni2L(MU-O2PH2)]ClO4 (2) or
      tetraphenylborate [Ni2L(MU-O2PH2)]BPh4 (3) salt. 3.MeCN crystallizes in the
      triclinic space group P1. The bisoctahedral [Ni2L(MU-O2PH2)](+) cation has a
      N3Ni(MU1,3-O2PH2)(MU-S)2NiN3 core structure with the hypophosphito ligand
      attached to the two Ni(II) ions in a MU1,3-bridging mode. The hypophosphito
      ligand is readily replaced by carboxylates, in agreement with a higher affinity
      of the [Ni2L](2+) dication for more basic oxoanions. Treatment of [Ni2L(MU
      O2PH2)]ClO4 with H2O2 or MCPBA results in the oxidation of the bridging thiolato
      to sulfonato groups. The hypophosphito group is not oxidized under these
      conditions due to the steric protection offered by the supporting ligand. An
      analysis of the temperature-dependent magnetic susceptibility data for 3 reveals
      the presence of ferromagnetic exchange interactions between the Ni(ii) (S = 1)
      ions with a value for the magnetic exchange coupling constant J of +22 cm(-1) (H
      = -2JS1S2). These results are additionally supported by DFT (density functional
      theory) calculations. 

PMID- 23126333
TI  - High-density cell systems incorporating polymer microspheres as
      microenvironmental regulators in engineered cartilage tissues.
AB  - To address the significant clinical need for tissue-engineered therapies for the
      repair and regeneration of articular cartilage, many systems have recently been
      developed using bioactive polymer microspheres as regulators of the chondrogenic
      microenvironment within high-density cell cultures. In this review, we highlight
      various densely cellular systems utilizing polymer microspheres as three
      dimensional (3D) structural elements within developing engineered cartilage
      tissue, carriers for cell expansion and delivery, vehicles for spatiotemporally
      controlled growth factor delivery, and directors of cell behavior via regulation
      of cell-biomaterial interactions. The diverse systems described herein represent
      a shift from the more traditional tissue engineering approach of combining cells
      and growth factors within a biomaterial scaffold, to the design of modular
      systems that rely on the assembly of cells and bioactive polymer microspheres as
      building blocks to guide the creation of articular cartilage. Cell-based assembly
      of 3D microsphere-incorporated structures represents a promising avenue for the
      future of tissue engineering.

PMID- 23126336
TI  - The impact of staff and service user gender on staff responses towards adults
      with intellectual disabilities who display aggressive behaviour.
AB  - BACKGROUND: The impact of staff and service user gender on responses of staff in
      intellectual disability (ID) services is poorly understood. The present study set
      out to assess the role of gender in influencing staff emotions, attributions and
      behavioural intentions in response to aggression displayed by adults with ID.
      METHOD: A new scale measuring staff behavioural intentions was developed. A two *
      two (staff gender * service user gender) between subjects design was used to
      compare the responses of day and residential support staff to physical aggression
      by a hypothetical service user. In response to a vignette depicting a service
      user with ID assaulting a member of staff, 160 respondents completed measures of
      affective responses, causal attributions and behavioural intentions while
      imagining themselves as the target of the service user's assault. RESULTS: Female
      participants reported feeling more fear/anxiety, more depression/anger and less
      confident/relaxed than male participants. The longer staff had worked with people
      with ID, the more likely they were to favour safety-focused behaviours. More
      confident female participants were less likely to favour safety-focused
      behaviours, but confidence had no effect on male participants' endorsement of
      these behaviours. Increased confidence in both was associated with lower
      agreement of safety-focused behaviours in relation to the female vignette,
      regardless of participant gender. The more control women believed the service
      user had over their behaviour, the more likely they were to choose safety-focused
      behaviours. Punitive behaviours were favoured more in response to the male rather
      than the female service user. Punitive behaviours were also favoured more by more
      junior staff and by participants who expected feeling more depressed/angry in
      response to the vignettes. CONCLUSIONS: Both staff and service user gender
      influenced staff responses to aggression, yet the latter played a smaller role
      than expected. The role of gender in staff-service user interactions should be
      the focus of further research and should be considered in service delivery.

PMID- 23126335
TI  - Visualization of odor-induced neuronal activity by immediate early gene
      expression.
AB  - BACKGROUND: Sensitive detection of sensory-evoked neuronal activation is a key to
      mechanistic understanding of brain functions. Since immediate early genes (IEGs)
      are readily induced in the brain by environmental changes, tracing IEG expression
      provides a convenient tool to identify brain activity. In this study we used in
      situ hybridization to detect odor-evoked induction of ten IEGs in the mouse
      olfactory system. We then analyzed IEG induction in the cyclic nucleotide-gated
      channel subunit A2 (Cnga2)-null mice to visualize residual neuronal activity
      following odorant exposure since CNGA2 is a key component of the olfactory signal
      transduction pathway in the main olfactory system. RESULTS: We observed rapid
      induction of as many as ten IEGs in the mouse olfactory bulb (OB) after olfactory
      stimulation by a non-biological odorant amyl acetate. A robust increase in
      expression of several IEGs like c-fos and Egr1 was evident in the glomerular
      layer, the mitral/tufted cell layer and the granule cell layer. Additionally, the
      neuronal IEG Npas4 showed steep induction from a very low basal expression level
      predominantly in the granule cell layer. In Cnga2-null mice, which are usually
      anosmic and sexually unresponsive, glomerular activation was insignificant in
      response to either ambient odorants or female stimuli. However, a subtle
      induction of c-fos took place in the OB of a few Cnga2-mutants which exhibited
      sexual arousal. Interestingly, very strong glomerular activation was observed in
      the OB of Cnga2-null male mice after stimulation with either the neutral odor
      amyl acetate or the predator odor 2, 3, 5-trimethyl-3-thiazoline (TMT).
      CONCLUSIONS: This study shows for the first time that in vivo olfactory
      stimulation can robustly induce the neuronal IEG Npas4 in the mouse OB and
      confirms the odor-evoked induction of a number of IEGs. As shown in previous
      studies, our results indicate that a CNGA2-independent signaling pathway(s) may
      activate the olfactory circuit in Cnga2-null mice and that neuronal activation
      which correlates to behavioral difference in individual mice is detectable by in
      situ hybridization of IEGs. Thus, the in situ hybridization probe set we
      established for IEG tracing can be very useful to visualize neuronal activity at
      the cellular level.

PMID- 23126337
TI  - Long-term survival of calcium phosphate-coated dental implants: a meta-analytical
      approach to the clinical literature.
AB  - BACKGROUND: Calcium phosphate ceramic coatings have the potential to compensate
      for challenging bone conditions such as delayed or impaired bone healing and low
      bone quantity or density. Thus, the increasing universal prevalence of subjects
      with such challenging bone conditions might be paralleled by an enhanced global
      use of calcium phosphate ceramic-coated dental implants. However, it is
      speculated that the long-term clinical survival of calcium phosphate-coated
      dental implants might be adversely affected by coating delamination. OBJECTIVE:
      The aims of the current review were (1) to systematically appraise and (2) to
      meta-analyse long-term survival data of calcium phosphate-coated dental implants
      in clinical trials. MATERIALS AND METHODS: An extensive search in the electronic
      databases of the National Library of Medicine (http://www.ncbi.nlm.nih.gov), The
      Cochrane Central Register of Controlled Trials and the ISI Web of Knowledge, was
      carried out for articles published between January 2000 and November 2011 to
      identify randomized controlled clinical trials, prospective clinical trials as
      well as retrospective analysis of cases (RA) presenting survival data on the
      topic of calcium phosphate-coated dental implants. Only publications in English
      were considered, and the search was narrowed to studies in humans with a follow
      up of at least 5 years only. Furthermore, the reference lists of related review
      articles and publications selected for inclusion in this review were
      systematically screened. The primary outcome variable was percentage annual
      failure rate (AFR), and the secondary outcome variable was percentage cumulative
      survival rate (CSR). RESULTS: The electronic search in the database of the
      National Library of Medicine, The Cochrane Central Register of Controlled Trials
      and the ISI Web of Knowledge, resulted in the identification of 385 titles. These
      titles were initially screened by the two independent reviewers for possible
      inclusion, resulting in 29 publications suitable for further consideration.
      Screening the abstracts led to 20 full-text articles. From these articles, 15
      reports were excluded. Finally, five of these original research reports could be
      selected for evaluation. No additional publications were identified by manual
      search. Thus, a total of five articles were included for analysis. Meta-analysis
      revealed that neither AFRs of calcium phosphate-coated dental implants increased
      progressively nor that long-term CSRs for calcium phosphate-coated dental
      implants were inferior to survival rates of noncoated implants. CONCLUSION: We
      conclude that (1) published long-term survival data for calcium phosphate-coated
      dental implants are very limited, (2) AFRs of calcium phosphate-coated dental
      implants do not increase progressively, and (3) long-term CSRs for calcium
      phosphate-coated dental implants are comparable to survival rates of noncoated
      implants.

PMID- 23126338
TI  - Levels of satisfaction with current chronic constipation treatment options in
      Europe - an internet survey.
AB  - BACKGROUND: Data on treatment satisfaction in European men and women with chronic
      constipation are limited. AIM: To assess satisfaction with current treatment
      among European men and women with chronic constipation. METHODS: An internet
      based survey was conducted in 2009 in 10 European countries: Austria, Germany,
      France, Ireland, Italy, Spain, Switzerland, the UK, Belgium and the Netherlands.
      Participants had self-reported chronic constipation (<3 bowel movements/week and
      >=1 symptoms for >=6 months of: pain during defecation; lumpy/hard faeces; and
      feeling of incomplete evacuation). Demographic data and disease history were
      collected. For participants using laxatives, drug name/class, satisfaction with
      treatment and interest in other treatments were collected. RESULTS: Of the 1941
      participants screened, 1355 had chronic constipation and met the inclusion
      criteria (chronic constipation population). The majority of the chronic
      constipation population who disclosed their sex (n = 811) were women (82%). Sixty
      eight per cent of respondents (n = 855/1255) reported using laxatives, with the
      proportion of laxative users differing between subsets. Twenty-eight per cent (n
      = 225/793) were (very) satisfied with their treatment, whereas 44% (n = 345/793)
      were neutral and 28% (n = 223/793) (very) dissatisfied. There was no relationship
      between type of laxative and degree of (dis)satisfaction. Interest in other
      treatments was high with 83% (n = 686/827) of respondents 'absolutely' or
      'probably' interested. Respondents dissatisfied with their treatment were more
      likely to be interested in other treatments. CONCLUSIONS: Laxative-use is common
      for chronic constipation. In this large survey, 28% of participants were
      dissatisfied with their treatment, with the majority interested in other
      treatments.

PMID- 23126340
TI  - First record of the fish pathogen Flavobacterium columnare genomovar II from
      bluegill, Lepomis macrochirus (Rafinesque), with observations on associated
      lesions.

PMID- 23126341
TI  - Doubly coarctate-stabilized carbenes: synthetic and computational studies.
AB  - Isoindazoles joined by an ethynyl linker to either a phenyltriazene or a
      phenyldiazene moiety were synthesized, and their subsequent reactivity was
      examined. Computations suggest that these molecules could rearrange at moderate
      temperatures via carbene intermediates that are doubly stabilized by coarctate
      conjugation. The experimental results corroborate the calculations, as the
      transient carbene can either be trapped with oxygen or undergo ring-opening to
      afford a rearranged product. Additional calculations illustrate some design
      principles that might lead to stable carbenes that are the global minimum on the
      coarctate hypersurface.

PMID- 23126339
TI  - Up-regulation of aldolase A and methylglyoxal production in adipocytes.
AB  - BACKGROUND AND PURPOSE: We previously reported that up-regulation of aldolase B,
      a key enzyme in fructose metabolism, was mainly responsible for vascular
      methylglyoxal (MG) overproduction under different pathological conditions. Here
      we investigated whether aldolase A, an enzyme of the glycolytic pathway, also
      caused MG overproduction in insulin-sensitive adipocytes. EXPERIMENTAL APPROACH:
      The relative contributions of different metabolic pathways or enzymes to MG
      generation were evaluated in cultured 3T3-L1 adipocytes. KEY RESULTS: Glucose (25
      mM) had no effect on aldolase A gene expression, but insulin (100 nM) up
      regulated aldolase A mRNA and protein levels in the absence or presence of 25 mM
      glucose in adipocytes. Treatment with insulin increased levels of basal or
      glucose (25 mM)-induced MG and glucose 6-phosphate. However, insulin, glucose (25
      mM) or their combination had no effect on cellular levels of sorbitol and
      fructose, but down-regulated gene expression of aldolase B to a similar extent,
      when compared with the control group. Incubation of 3T3-L1 adipocytes with
      fructose, acetone, acetol, threonine or glycine (25 mM), with or without insulin
      did not alter cellular MG levels. The elevated MG levels induced by insulin,
      glucose (25 mM) or their combination in adipocytes was completely reduced by
      siRNA knock down of aldolase A or application of 2-deoxy-D-glucose (a non
      specific inhibitor of glucose uptake and glycolysis), but not by knock down of
      aldolase B. CONCLUSION AND IMPLICATIONS: Insulin enhanced MG overproduction in
      insulin-sensitive adipocytes by up-regulating aldolase A, a mechanism that could
      be involved in the development of insulin resistance and obesity.

PMID- 23126342
TI  - Factors governing the conformational tendencies of C(alpha)-ethylated alpha-amino
      acids: chirality and side-chain size effects.
AB  - The intrinsic conformational properties of the N-acetyl-N'-methylamide
      derivatives of d-C(alpha)-ethylglycine (Abu), d-C(alpha)-methyl-C(alpha)
      ethylglycine (Iva), and C(alpha,alpha)-diethylglycine (Deg) have been
      investigated using quantum mechanical calculations in the gas phase and in
      chloroform, dichloromethane and aqueous solutions. Although the large number of
      flexible dihedral angles results in many minimum energy conformations, only a few
      of them are energetically representative because of the repulsive interactions
      between the ethyl groups and the backbone atoms. The conformational restrictions
      imposed by such repulsions increase as follows: Abu < Iva < Deg. The most
      important characteristics of the investigated residues are as follows: (i) the
      conformation tendencies of Abu resemble those of standard residues with similar
      constitution (e.g., Val or Leu); (ii) the properties of Iva are relatively
      similar to those of C(alpha,alpha)-dimethylglycine, which is the simplest
      C(alpha,alpha)-dialkylated alpha-amino acid, even though the former is more
      restricted than the latter; (iii) the conformational flexibility of Deg is even
      lower than that of C(alpha,alpha)-dialkylated residues with bulkier side groups
      (e.g., C(alpha,alpha)-diphenylglycine and C(alpha,alpha)-dibenzylglycine).

PMID- 23126343
TI  - Perceived antecedents of marital satisfaction among Turkish, Turkish-Dutch, and
      Dutch couples.
AB  - We studied mainstream couples in The Netherlands and Turkey as well as Turkish
      Dutch immigrant couples to address cultural factors associated with marital
      satisfaction. A total of 13 Turkish (mainstream couples living in Turkey), 19
      Turkish-Dutch (Turkish immigrant couples living in The Netherlands), and 17 Dutch
      (mainstream couples living in The Netherlands) married dyads (total of 98
      individuals) were independently interviewed about positive and negative
      characteristics of marriages, determinants of general marital satisfaction and
      dissatisfaction, spousal communication, marital conflict, and marital roles.
      Multivariate tests revealed ethnic group differences on all marriage-related
      domains except the conflict resolution strategies. However, univariate analyses
      showed differences in few themes within domains; main differences were assessed
      between the Turkish/Turkish-Dutch (who put more emphasis on children and
      economical aspects) and Dutch couples (who put more emphasis on behavior, and
      personality of the spouse, reciprocity, emotional sharing, and psychological
      roles). Turkish-Dutch couples were more similar to Turkish than to Dutch couples.
      Results were discussed in light of the socioeconomic development and cultural
      value theories, which are believed to provide a useful framework for
      understanding the role of culture in marital satisfaction. 

PMID- 23126344
TI  - How well do we care for patients with hypertension?

PMID- 23126345
TI  - Blood pressure measurement device, number and timing of visits, and intra
      individual visit-to-visit variability of blood pressure.
AB  - Visit-to-visit variability (VVV) of blood pressure is associated with
      cardiovascular disease. The authors examined the effects of visit number and
      timing and automated or manual measurement device on VVV in the placebo arm of
      the Trial of Preventing Hypertension (TROPHY) (N=225) and simulations. VVV was
      assessed using intra-individual standard deviation (SD), range, maximum,
      coefficient of variation, successive variation, and average real variability of
      systolic blood pressure. VVV increased with number of visits used to calculate it
      in the TROPHY population (P for trend <.05 for all metrics) and simulations.
      Using consecutive visits in TROPHY, average SD was 5.6 mm Hg from 3 visits, 6.8
      mm Hg from 7 visits, and 7.7 mm Hg from 18 visits. When 7 visits were spread out
      across 4 years, the average SD was higher (7.5 mm Hg) than when visits were
      consecutive over 18 months (P<.001). SD was higher using a single blood pressure
      measurement per visit (compared with the mean of 3 measurements per visit P<.001)
      and with automated vs manual devices (P<.001). In summary, number and timing of
      visits and device used to measure blood pressure influence VVV and need to be
      considered when designing, interpreting, and comparing studies.

PMID- 23126346
TI  - Impact of the number of blood pressure measurements on blood pressure
      classification in US adults: NHANES 1999-2008.
AB  - Clinical guidelines recommend averaging >= 2 blood pressure (BP) measurements on
      each visit. Only one BP is measured on many clinical visits, especially if the
      value is <120/<80 mm Hg, ie, normal. The impact of this practice on accurate
      assignment of BP category is incompletely defined. Data were analyzed from 22,641
      adults 18 years and older who had 3 BP readings in the National Health and
      Nutrition Examination Surveys 1999-2008. BP category defined by initial
      measurement was compared with the category determined by mean of the first and
      second, first through third, and second and third readings. Among 8553
      nonhypertensive patients with initial BP <120/<80 mm Hg, 2.9%, 3.3%, and 6.7%,
      respectively, were reclassified as prehypertensive, ie, BP 120-139/80-89 mm Hg,
      and two patients as stage 1 hypertension (140-159/90-99 mm Hg). In 733 treated
      hypertensive patients with initial BP <120/<80 mm Hg, 5.1%-8.9% were reclassified
      as prehypertensive and only one patient as hypertensive. Among nonhypertensive
      and hypertensive patients with initial BP in the prehypertensive range, 8.0%
      23.6% were reclassified as normal. Among stage 1 and 2 hypertensive patients
      based on initial BP, 18.2%-33.5% were reclassified to lower BP categories. By
      multivariable logistic regression, older age and higher systolic and diastolic BP
      were associated with reclassification to a lower BP category. In nonhypertensive
      and hypertensive patients with normal initial BP values, one BP measurement
      appears adequate as <10% are re-classified as prehypertensive and <0.5% as
      hypertensive. In contrast, patients with an initial BP above normal are often
      reclassified to a lower category, which supports recommendations for additional
      measurements.

PMID- 23126347
TI  - Cost-effectiveness evaluation of a collaborative patient education hypertension
      intervention in Utah.
AB  - This study analyzed the cost-effectiveness of a patient hypertension education
      intervention that provided patient education through interactive voice response
      technology and distribution of automated blood pressure monitors to high-risk
      plan members with uncontrolled hypertension. A total of 17,318 members were
      identified with hypertension in an administrative database. The study sample
      consisted of all 534 high-risk hypertensive plan members who received blood
      pressure monitors. Using data on activity-based program costs and changes in
      hypertension control, this study modeled the intervention's cost-effectiveness
      relative to no intervention. The intervention was estimated to have brought
      hypertension under control in 151 patients during the study year. Across all 534
      participants in 1 year, 0.3 events (acute myocardial infarction, stroke,
      congestive heart failure, and renal failure) were avoided and 2.77 life-years
      were gained (LYG). The incremental cost-effectiveness ratio (ICER) for the
      intervention compared with no intervention was $767 per person brought under
      control or $41,927 per LYG. If the gains in hypertension control from 1 year's
      investment were assumed to last 10 years, the 10-year ICER relative to no
      intervention was $1857 per LYG. The intervention is a cost-effective strategy to
      address hypertension and can serve as a model for future innovations.

PMID- 23126348
TI  - Lifestyle educational program strongly increases compliance to nonpharmacologic
      intervention in hypertensive patients: a 2-year follow-up study.
AB  - The authors investigated the efficacy of a lifestyle educational program,
      organized in small group meetings, in improving the outcome of a nonpharmacologic
      intervention. One hundred and eighty-eight hypertensive patients with stable
      blood pressure (BP) levels and drug therapy in the previous 6 months were
      randomly divided into educational care (EC) and usual care (UC) groups. They were
      followed at 3-month intervals up to 2 years. In addition to the visits in an
      outpatient clinic, patients in the EC program participated in small group
      meetings in order to improve their knowledge of the disease and reinforce their
      motivation for treatment. At baseline, EC and UC groups were similar for age,
      sex, body mass index (BMI), blood pressure (BP) levels, and pharmacologic
      treatment. Patients in the EC group had significantly reduced total energy, total
      and saturated fats, and sodium intake. Physical activity was significantly
      increased in the EC group as well. At the end of the 1-year follow-up, BMI
      (P<.001), visceral fat (P<.001), and BP (P<.001) were significantly lower in the
      EC group compared with the UC group. Pharmacologic treatment during the study was
      similar for all classes of drugs apart from diuretics whose dose was higher in
      the UC group at the end of the study.

PMID- 23126349
TI  - Changes in aortic pulse wave velocity in hypertensive postmenopausal women:
      comparison between a calcium channel blocker vs angiotensin receptor blocker
      regimen.
AB  - Postmenopausal women are at greater risk for hypertension-related cardiovascular
      disease. Antihypertensive therapy may help alleviate arterial stiffness that
      represents a potential modifiable risk factor of hypertension. This randomized
      controlled study investigated the difference between an angiotensin receptor
      blocker and a calcium channel blocker in reducing arterial stiffness. Overall,
      125 postmenopausal hypertensive women (age, 61.4 +/- 6 years; systolic blood
      pressure/diastolic blood pressure [SBP/DBP], 158 +/- 11/92 +/- 9 mm Hg) were
      randomized to valsartan 320 mg +/- hydrochlorothiazide (HCTZ) (n = 63) or
      amlodipine 10 mg +/- HCTZ (n = 62). The primary outcome was carotid-to-femoral
      pulse wave velocity (PWV) changes after 38 weeks of treatment. Both treatments
      lowered peripheral blood pressure (BP) (-22.9/-10.9 mm Hg for valsartan and 
      25.2/-11.7 mm Hg for amlodipine, P = not significant) and central BP (-15.7/-7.6
      mm Hg for valsartan and -19.2/-10.3 mm Hg for amlodipine, P<.05 for central DBP).
      Both treatments similarly reduced the carotid-femoral PWV (-1.9 vs -1.7 m/s; P =
      not significant). Amlodipine was associated with a higher incidence of peripheral
      edema compared with the valsartan group (77% vs 14%, P<.001). BP lowering in
      postmenopausal women led to a reduction in arterial stiffness as assessed by PWV
      measurement. Both regimens reduced PWV to a similar degree after 38 weeks of
      treatment despite differences in central BP lowering, suggesting that the effect
      of valsartan on PWV is mediated through nonhemodynamic effects.

PMID- 23126350
TI  - Elderly hypertensives: how are they different?
AB  - Once considered an inconsequential part of the aging process, the development of
      isolated systolic hypertension represents a late manifestation of increased
      elastic artery stiffness and is the predominant hypertensive subtype in the
      middle-aged and elderly populations. Its inherent increased risk for vascular
      events, such as coronary heart disease, stroke, heart failure, peripheral artery
      disease, chronic kidney disease, and dementia, highlights the importance of its
      control. The purpose of this short review is to summarize how hypertension is
      different in the elderly when compared with "essential hypertension" in younger
      adults. The emphasis will be on the multiple ways that increased artery stiffness
      affects the natural history and clinical manifestations of hypertension in the
      elderly.

PMID- 23126351
TI  - The dilemma of nocturnal blood pressure.
AB  - During the past decades, blood pressure (BP) measurement technique has evolved
      rapidly from the traditionally manual measuring to fully automatic monitoring. In
      terms of management of BP, there have been tremendous changes from the
      controlling of daytime BP, nondipping pattern to nocturnal BP (NBP). Since the
      focus has turned to NBP, a number of dilemmas of NBP measurement have gradually
      emerged in clinical practice and research settings, including methods for
      monitoring NBP, different period definition of nocturnal time, different
      diagnostic thresholds of abnormal NBP, whether to control abnormal NBP, and how
      to manage abnormal NBP. Currently, these issues have hindered progress in the
      appropriate management of hypertensive patients. Therefore, the purpose of this
      review is to concisely discuss the dilemmas of NBP.

PMID- 23126352
TI  - Alcohol consumption and the risk of hypertension in men and women: a systematic
      review and meta-analysis.
AB  - Heavy alcohol intake increases the risk of hypertension, but the relationship
      between light to moderate alcohol consumption and incident hypertension remains
      controversial. The authors sought to analyze the dose-response relationship
      between average daily alcohol consumption and the risk of hypertension via
      systematic review and meta-analysis. Electronic databases were searched for
      prospective control studies examining quantitative measurement of alcohol
      consumption and biological measurement of outcome. The primary endpoint was the
      risk of developing hypertension based on alcohol consumption. The level of
      alcohol consumption from each study was assigned to categorical groups based on
      the midpoint of their alcohol consumption classes to make possible the comparison
      of heterogeneous classification of alcohol intake. A total of 16 prospective
      studies (33,904 men and 193,752 women) were included in the analysis. Compared
      with nondrinkers, men with alcohol consumption with <10 g/d and 11 to 20 g/d had
      a trend toward increased risk of hypertension (relative risk [RR], 1.03; 95%
      confidence interval [CI], 0.94-1.13; P=.51) and (RR, 1.15; 95% CI, 0.99-1.33;
      P=.06), respectively, whereas a significantly increased risk of hypertension was
      found with heavy alcohol consumption of 31 to 40 g/d (RR, 1.77; 95% CI, 1.39
      2.26; P<.001) and >50 g/d (RR, 1.61; 95% CI, 1.38-1.87; P<.001). Among women, the
      meta-analysis indicated protective effects at <10 g/d (RR, 0.87; 95% CI, 0.82
      0.92; P<.001) and a trend toward decreased risk of hypertension with alcohol
      consumption 11 to 20 g/d (RR, 0.9; 95% CI, 0.87-1.04; P=.17), whereas a
      significantly increased risk of hypertension was indicated with heavy alcohol
      consumption of 21 to 30 g/d (RR, 1.16; 95% CI, 0.91-1.46; P=.23) and 31 to 40 g/d
      (RR, 1.19; 95% CI, 1.07-1.32; P=.002). In men, heavy alcohol consumption is
      associated with increased risk of hypertension, whereas there is a trend toward
      increased risk of hypertension with low and moderate alcohol consumption. The
      relationship between alcohol consumption and hypertension is J-shaped in women.
      Limiting alcohol intake should be advised for both men and women.

PMID- 23126353
TI  - Renal denervation in a hypertensive patient with end-stage renal disease and
      small arteries: a direction for future research.
AB  - Sympathetic overactivity plays a crucial pathogenetic role in the maintenance and
      aggravation of arterial hypertension in patients with end-stage renal disease
      (ESRD). Renal denervation has been shown to be effective and safe in reducing
      blood pressure (BP) in patients with treatment-resistant hypertension; however,
      there are only case reports in hypertensive patients with ESRD and data are
      lacking about possibility of renal denervation in small renal arteries. A woman
      with uncontrolled treatment-resistant hypertension on chronic hemodialysis
      underwent bilateral native kidney, catheter-based renal denervation. Both native
      renal arteries were <4 mm. After 6 months without any change of antihypertensive
      medication or hemodialysis parameters, the authors observed a remarkable BP
      reduction of 38/30 mm Hg (from baseline 172/100 mm Hg to 134/70 mm Hg) as
      evaluated by 24-hour ambulatory BP monitoring. The authors report that renal
      denervation seems to be effective in controlling hypertension in patients with
      ESRD, even in cases of small renal arteries.

PMID- 23126354
TI  - Recurrent hypertensive cerebral hemorrhages in a boy caused by a reninoma: rare
      manifestations and distinctive electron microscopy findings.
AB  - Recurrent cerebral hemorrhages caused by hypertension secondary to reninoma are
      extremely rare in children. Because of its detrimental effects on children's
      health, the importance of early diagnosis of and treatment for reninoma should be
      emphasized. Here, the authors present a 10-year-old boy with intermittent
      headaches and neurologic deficiency symptoms caused by hypertension. A reninoma
      in the right kidney was detected and successfully treated with laparoscopic
      partial nephrectomy. Two cell types were revealed in the tumor tissue under
      electron microscopy: renin secreting tumor cells and mast cells. This rare case
      expands our knowledge of hypertension in children and provides direct evidence
      that mast cells may infiltrate reninoma.

PMID- 23126355
TI  - Some questionable conclusions in the article "Dietary supplements and
      hypertension: potential benefits and precautions".

PMID- 23126356
TI  - Comparative effectiveness of ACEIs and ARBs.

PMID- 23126357
TI  - Is isolated systolic hypertension worse than combined systolic/diastolic
      hypertension?
AB  - New developments in cardiovascular translational sciences have significantly
      advanced our understanding of the endovascular biology of blood pressure.
      Reductions in vascular elasticity and vessel compliance of conduit arteries are
      key components of both ISH and SDH. Vascular changes from the matrix
      metalloproteinase family of enzymes are involved in arterial wall remodeling and
      vascular stiffness. This new translational information helps further our
      understanding of both ISH and SDH.

PMID- 23126358
TI  - The 50th anniversary of the Kefauver-Harris Amendments: efficacy assessment and
      the randomized clinical trial.

PMID- 23126359
TI  - Should we be recommending vitamin D supplementation for hypertension and
      cardiovascular disease prevention?

PMID- 23126360
TI  - Exposure to air pollution increases the incidence of hypertension and diabetes in
      black women living in Los Angeles.

PMID- 23126361
TI  - Lower cyclooxygenase-2 expression is associated with recurrence of solitary non
      muscle invasive bladder carcinoma.
AB  - BACKGROUND: A new modality is necessary to prevent recurrence of superficial
      bladder cancer after complete transurethral resection because of the high
      recurrence rate even with current prophylaxis protocols. METHODS: In order to
      analyze the predictive value of cyclooxygenase-2 (COX-2) expression and tumor
      infiltrating lymphocytes (TILs) in recurrence of this disease tumor specimens
      from 127 patients with solitary papillary non-muscle invasive bladder cancer
      (NMIBC), 78 with recurrent disease and 49 without recurrence during follow up of
      minimum 5 years, were retrieved for tissue microarrays construction and
      immunohistochemical analysis. COX-2 expression was scored according to Allred's
      scoring protocol, while presence of TILs was categorized as absent (no) or
      present (yes) on whole tissue sections. RESULTS: COX-2 immunoreactivity was
      presented in 70 (71%), weak in 16% and strong in 55% of cases, while 29 (29%)
      tumors were negative. TILs were present in 64 (58%) NMIBC, while 44 cases (41%)
      did not reveal mononuclear infiltration in tumoral stroma. Statistical analysis
      demonstrated a higher proportion of patients with recurrence in the group with
      the COX-2 score 0, and lower in the group with score 2 (p=0.0001, p=0.0101,
      respectively). In addition, a higher proportion of recurrent patients in the
      group with no TILs, and lower proportion in the group with TILs were found
      (p=0.009, p=0.009, respectively). Univariate and multivariate analysis revealed
      overexpression of COX-2 and presence of TILs as negative predictors. CONCLUSION:
      Patients with lower COX-2 expression and absence of TILs in NMIBC need to be
      followed up more vigorously and probably selected for adjuvant therapy. VIRTUAL
      SLIDE: The virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1411318819790406.

PMID- 23126362
TI  - The laxative effects of Maesil (Prunus mume Siebold & Zucc.) on constipation
      induced by a low-fibre diet in a rat model.
AB  - Maesil (the fruit of Prunus mume Siebold & Zucc.) has long been used as an
      alternative medicine and functional food in Korea and Japan for preventive and
      therapeutic purposes. We examined the laxative effect of unripe Maesil (UM) and
      ripe Maesil (RM) in a rat model on constipation induced by a low-fibre diet and
      the possible mechanisms of Maesil in the rat colon. In vivo studies were
      conducted on the low-fibre diet-induced constipation rat model, and isolated rat
      colon was used in in vitro experiments to measure the changes in spontaneous
      colon contraction generated by Maesil and organic acids as standard and effectual
      ingredients, respectively. The aqueous extract of both UM and RM applied orally
      (100 and 300 mg/kg) produced significant increase of faeces frequency (p < 0.05)
      and moisture (p < 0.001). Moreover, the number faecal pellets number was reduced
      (p < 0.05) in the distal colons of the Maesil-treated rats. Gastrointestinal (GI)
      motility, measured by charcoal meal, was activated more fully by UM than in the
      low-fibre diet group. Both UM and RM and its organic acids produced a dose
      dependent stimulation of the spontaneous contractile amplitude (p < 0.001) and
      frequency (p < 0.01) of the isolated rat colon. Although both UM and RM were an
      effective laxative, the RM was significantly more effective than the UM in the in
      vivo and in vitro constipation experiments because of the changes in the
      composition of organic acids during the ripening of the fruit. Our results
      demonstrated that Maesil was effective in promoting the frequency of defaecation
      and contraction of the rat colon, which provided scientific basis to support the
      use of Maesil as potential therapeutics in treating constipation.

PMID- 23126363
TI  - High-throughput immunomagnetic scavenging technique for quantitative analysis of
      live VX nerve agent in water, hamburger, and soil matrixes.
AB  - We have developed a novel immunomagnetic scavenging technique for extracting
      cholinesterase inhibitors from aqueous matrixes using biological targeting and
      antibody-based extraction. The technique was characterized using the
      organophosphorus nerve agent VX. The limit of detection for VX in high
      performance liquid chromatography (HPLC)-grade water, defined as the lowest
      calibrator concentration, was 25 pg/mL in a small, 500 MUL sample. The method was
      characterized over the course of 22 sample sets containing calibrators, blanks,
      and quality control samples. Method precision, expressed as the mean relative
      standard deviation, was less than 9.2% for all calibrators. Quality control
      sample accuracy was 102% and 100% of the mean for VX spiked into HPLC-grade water
      at concentrations of 2.0 and 0.25 ng/mL, respectively. This method successfully
      was applied to aqueous extracts from soil, hamburger, and finished tap water
      spiked with VX. Recovery was 65%, 81%, and 100% from these matrixes,
      respectively. Biologically based extractions of organophosphorus compounds
      represent a new technique for sample extraction that provides an increase in
      extraction specificity and sensitivity.

PMID- 23126364
TI  - Health-related quality of life after stroke: a 2-year prospective cohort study in
      Wuhan, China.
AB  - Little is known about health-related quality of life (HRQoL) after stroke in
      Chinese populations. We conducted the present study to evaluate HRQoL after
      stroke in a group of Chinese patients. We followed 114 patients diagnosed with a
      first-ever stroke for 2 years. The HRQoL at discharge, 1 year poststroke, and 2
      years poststroke was evaluated with the medical outcome short form 36. After a 2
      year follow-up, there were 92 (88.5%) survivors. All eight domains of the HRQoL
      had the lowest scores at discharge, greatly improved over the first year after
      discharge, and showed continuous improvement. The HRQoL of patients after stroke
      significantly improved in two mental health domains (social function and mental
      health) and all four physical health domains 2 years after discharge. However,
      patients with stroke still had significantly lower scores in every domain than an
      age-matched reference group even 2 years after discharge. Age, sex, and
      activities of daily living were associated with HRQoL in the mental or physical
      domain in patients with stroke. Our results suggest that HRQoL greatly improved 2
      years after discharge in patients with stroke. This study also confirmed the
      usefulness of the HRQoL assessment for prognosis evaluation in patients after
      stroke. Further studies from Chinese populations are still warranted.

PMID- 23126365
TI  - Structural characterization of the mechanism through which human glutamic acid
      decarboxylase auto-activates.
AB  - Imbalances in GABA (gamma-aminobutyric acid) homoeostasis underlie psychiatric
      and movement disorders. The ability of the 65 kDa isoform of GAD (glutamic acid
      decarboxylase), GAD65, to control synaptic GABA levels is influenced through its
      capacity to auto-inactivate. In contrast, the GAD67 isoform is constitutively
      active. Previous structural insights suggest that flexibility in the GAD65
      catalytic loop drives enzyme inactivation. To test this idea, we constructed a
      panel of GAD65/67 chimaeras and compared the ability of these molecules to auto
      inactivate. Together, our data reveal the important finding that the C-terminal
      domain of GAD plays a key role in controlling GAD65 auto-inactivation. In support
      of these findings, we determined the X-ray crystal structure of a GAD65/67
      chimaera that reveals that the conformation of the catalytic loop is intimately
      linked to the C-terminal domain.

PMID- 23126367
TI  - Grapefruit juice markedly increases the plasma concentrations and antiplatelet
      effects of ticagrelor in healthy subjects.
AB  - AIM: This study examined the effects of grapefruit juice on the new P2Y12
      inhibitor ticagrelor, which is a substrate of CYP3A4 and P-glycoprotein. METHODS:
      In a randomized crossover study, 10 healthy volunteers ingested 200 ml of
      grapefruit juice or water thrice daily for 4 days. On day 3, they ingested a
      single 90 mg dose of ticagrelor. RESULTS: Grapefruit juice increased ticagrelor
      geometric mean peak plasma concentration (Cmax ) to 165% (95% confidence interval
      147, 184%) and area under the concentration-time curve (AUC(0,infinity)) to 221%
      of control (95% confidence interval 200, 245%). The Cmax and AUC(0,34 h) (P <
      0.05) but not the AUC(0,infinity) of the active metabolite C12490XX were
      decreased significantly. Grapefruit juice had a minor effect on ticagrelor
      elimination half-life prolonging it from 6.7 to 7.2 h (P = 0.036). In good
      correlation with the elevated plasma ticagrelor concentrations, grapefruit juice
      enhanced the antiplatelet effect of ticagrelor, assessed with VerifyNow(r) and
      Multiplate(r) methods, and postponed the recovery of platelet reactivity.
      CONCLUSIONS: Grapefruit juice increased ticagrelor exposure by more than two
      fold, leading to an enhanced and prolonged ticagrelor antiplatelet effect. The
      grapefruit juice-ticagrelor interaction seems clinically important and indicates
      the significance of intestinal metabolism to ticagrelor pharmacokinetics.

PMID- 23126368
TI  - Niche opportunities and invasion dynamics in a desert annual community.
AB  - Although many factors influence the ability of exotics to invade successfully,
      most studies focus on only a few variables to explain invasion; attempts at
      theoretical synthesis are largely untested. The niche opportunities framework
      proposes that the demographic success of an invader is largely affected by the
      availability of resources and the abundance of its enemies. Here, we use a 31
      year study from a desert ecosystem to examine the niche opportunities framework
      via the invasion of the annual plant Erodium cicutarium. While the invader
      remained rare for two decades, a decline in granivory combined with an ideal
      climate window created an opportunity for E. cicutarium to escape control and
      become the dominant annual plant in the community. We show that fluctuations in
      consumption and resources can create niche opportunities for invaders and
      highlight the need for additional long-term studies to track the influence of
      changing climate and community dynamics on invasions.

PMID- 23126369
TI  - Evaluation of misindexing of EBSD patterns in a ferritic steel.
AB  - The systematic misindexing caused by pseudo-symmetry Kikuchi diffraction patterns
      in automated Electron Backscatter Diffraction analysis has been studied in a 9Cr
      1Mo ferritic steel. Grains with its [1 1 1] directed towards detector centre were
      found to be prone to misindexing, and the solutions exhibit a relative
      orientation of +/-30 degrees  and 60 degrees  about the common [1 1 1] axis (as
      compared to the true orientation). Fictitious boundaries were detected within
      such grains, which satisfy the Sigma3 or Sigma13b type coincidence site lattice
      boundary criteria. Misindexing rate was reduced with more than six detected
      bands, but 30 degrees  rotated solution was comparatively more persistent, as the
      additional bands of (3 1 0)-type exhibited a nearly good pattern match. Increase
      in detector collection angle to 0.96 sr or number of detected bands to nine were
      found to be beneficial in preventing the misindexing problem.

PMID- 23126370
TI  - Applying a framework for assessing the health system challenges to scaling up
      mHealth in South Africa.
AB  - BACKGROUND: Mobile phone technology has demonstrated the potential to improve
      health service delivery, but there is little guidance to inform decisions about
      acquiring and implementing mHealth technology at scale in health systems. Using
      the case of community-based health services (CBS) in South Africa, we apply a
      framework to appraise the opportunities and challenges to effective
      implementation of mHealth at scale in health systems. METHODS: A qualitative
      study reviewed the benefits and challenges of mHealth in community-based services
      in South Africa, through a combination of key informant interviews, site visits
      to local projects and document reviews. Using a framework adapted from three
      approaches to reviewing sustainable information and communication technology
      (ICT), the lessons from local experience and elsewhere formed the basis of a
      wider consideration of scale up challenges in South Africa. RESULTS: Four key
      system dimensions were identified and assessed: government stewardship and the
      organisational, technological and financial systems. In South Africa, the
      opportunities for successful implementation of mHealth include the high
      prevalence of mobile phones, a supportive policy environment for eHealth,
      successful use of mHealth for CBS in a number of projects and a well-developed
      ICT industry. However there are weaknesses in other key health systems areas such
      as organisational culture and capacity for using health information for
      management, and the poor availability and use of ICT in primary health care. The
      technological challenges include the complexity of ensuring interoperability and
      integration of information systems and securing privacy of information. Finally,
      there are the challenges of sustainable financing required for large scale use of
      mobile phone technology in resource limited settings. CONCLUSION: Against a
      background of a health system with a weak ICT environment and limited
      implementation capacity, it remains uncertain that the potential benefits of
      mHealth for CBS would be retained with immediate large-scale implementation.
      Applying a health systems framework facilitated a systematic appraisal of
      potential challenges to scaling up mHealth for CBS in South Africa and may be
      useful for policy and practice decision-making in other low- and middle-income
      settings.

PMID- 23126371
TI  - Microcarriers designed for cell culture and tissue engineering of bone.
AB  - Microspherical particulates have been an attractive form of biomaterials that
      find usefulness in cell delivery and tissue engineering. A variety of
      compositions, including bioactive ceramics, degradable polymers, and their
      composites, have been developed into a microsphere form and have demonstrated the
      potential to fill defective bone and to populate tissue cells on curved matrices.
      To enhance the capacity of cell delivery, the conventional solid form of spheres
      is engineered to have either a porous structure to hold cells or a thin shell to
      in-situ encapsulate cells within the structure. Microcarriers can also be a
      potential reservoir system of bioactive molecules that have therapeutic effects
      in regulating cell behaviors. Due to their specific form, advanced technologies
      to culture cell-loaded microcarriers are required, such as simple agitation or
      shaking, spinner flask, and rotating chamber system. Here, we review
      systematically, from material design to culture technology, the microspherical
      carriers used for the delivery of cells and tissue engineering, particularly of
      bone.

PMID- 23126372
TI  - Deficiency in mural vascular cells coincides with blood-brain barrier disruption
      in Alzheimer's disease.
AB  - Neurovascular dysfunction contributes to Alzheimer's disease (AD).
      Cerebrovascular abnormalities and blood-brain barrier (BBB) damage have been
      shown in AD. The BBB dysfunction can lead to leakage of potentially neurotoxic
      plasma components in brain that may contribute to neuronal injury. Pericytes are
      integral in maintaining the BBB integrity. Pericyte-deficient mice develop a
      chronic BBB damage preceding neuronal injury. Moreover, loss of pericytes was
      associated with BBB breakdown in patients with amyotrophic lateral sclerosis.
      Here, we demonstrate a decrease in mural vascular cells in AD, and show that
      pericyte number and coverage in the cortex and hippocampus of AD subjects
      compared with neurologically intact controls are reduced by 59% and 60% (P <
      0.01), and 32% and 33% (P < 0.01), respectively. An increase in extravascular
      immunoglobulin G (IgG) and fibrin deposition correlated with reductions in
      pericyte coverage in AD cases compared with controls; the Pearson's correlation
      coefficient r for the magnitude of BBB breakdown to IgG and fibrin vs. reduction
      in pericyte coverage was -0.96 (P < 0.01) and -0.81 (P < 0.01) in the cortex,
      respectively, and -0.86 (P < 0.01) and -0.98 (P < 0.01) in the hippocampus,
      respectively. Thus, deficiency in mural vascular cells may contribute to
      disrupted vascular barrier properties and resultant neuronal dysfunction during
      AD pathogenesis.

PMID- 23126374
TI  - Real-world health care costs of relapsed/refractory multiple myeloma during the
      era of novel cancer agents.
AB  - WHAT IS KNOWN AND OBJECTIVE: High costs of novel agents increasingly put pressure
      on limited healthcare budgets. Demonstration of their real-world costs and cost
      effectiveness is often required for reimbursement. However, few published
      economic evaluations of novel agents for multiple myeloma exist. Moreover,
      existing cost analyses were heavily based on conventionally treated patients. We
      investigated real-world health care costs of relapsed/refractory multiple myeloma
      in Dutch daily practice. METHODS: A retrospective medical chart review was
      conducted for 139 patients treated between January 2001 and May 2009. Total
      monthly costs attributable to each cost component were described across all
      regimens and for bortezomib-, thalidomide- and lenalidomide-based treatment
      regimens. RESULTS: Mean monthly total costs (?3,981) varied depending on the
      sequence of therapy (range: ?442-?31,318). Significant cost drivers across all
      regimens included costs of therapy and hospital admissions. The acquisition costs
      for novel agents in particular accounted for 32% of mean total monthly costs.
      Prognostic factors associated with increased mean total monthly costs in
      multivariate regression analysis included low platelet counts (P = 0.01) and
      worsening performance status (P < 0.001). Mean total monthly costs of bortezomib-
      and lenalidomide-based regimens were significantly higher than those for
      thalidomide-based regimens in second, third and fourth treatment line. WHAT IS
      NEW AND CONCLUSIONS: Real-world costs during treatment of relapsed/refractory
      multiple myeloma vary greatly. Cost drivers include hospital admissions and
      acquisition costs of novel agents. Costs also vary by prognostic factors and
      treatment-related resource use. Future studies assessing the costs of combination
      therapy consisting of two or more novel agents are encouraged.

PMID- 23126373
TI  - Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine
      kinase, in cancer patients.
AB  - BACKGROUND AND PURPOSE: Famitinib is a novel multi-targeted receptor tyrosine
      kinase inhibitor under development for cancer treatment. This study aims to
      characterize the metabolic and bioactivation pathways of famitinib. EXPERIMENTAL
      APPROACH: The metabolites in human plasma, urine and feces were identified via
      ultra-high performance liquid chromatography-quadrupole-time of flight-mass
      spectrometry and confirmed using synthetic standards. Biotransformation and
      bioactivation mechanisms were investigated using microsomes, recombinant
      metabolic enzymes and hepatocytes. KEY RESULTS: Famitinib was extensively
      metabolized after repeated oral administrations. Unchanged famitinib was the
      major circulating material, followed by N-desethylfaminitib (M3), whose steady
      state exposure represented 7.2 to 7.5% that of the parent drug. Metabolites in
      the excreta were mainly from oxidative deamination (M1), N-desethylation (M3),
      oxidative defluorination (M7), indolylidene hydroxylation (M9-1 and M9-5) and
      secondary phase-II conjugations. CYP3A4/5 was the major contributor to M3
      formation, CYP3A4/5 and aldehyde dehydrogenase to M1 formation and CYP1A1/2 to
      M7, M9-1 and M9-5 formations. Minor cysteine conjugates were observed in the
      plasma, urine and feces, implying the formation of reactive intermediate(s). In
      vitro microsomal studies proved that famitinib was bioactivated through
      epoxidation at indolylidene by CYP1A1/2 and spontaneously defluorinated
      rearrangement to afford a quinone-imine species. A correlation between famitinib
      hepatotoxicity and its bioactivation was observed in the primary human
      hepatocytes. CONCLUSION AND IMPLICATIONS: Famitinib is well absorbed and
      extensively metabolized in cancer patients. Multiple enzymes, mainly CYP3A4/5 and
      CYP1A1/2, are involved in famitinib metabolic clearance. The quinone-imine
      intermediate formed through bioactivation may be associated with famitinib
      hepatotoxicity. Co-administered CYP1A1/2 inducers or inhibitors may potentiate or
      suppress its hepatotoxicity.

PMID- 23126375
TI  - Mechanistic and exploratory investigations into the synthesis of 1,3,5
      triaroylbenzenes from 1-aryl-2-propyn-1-ones and 1,3,5-triacetylbenzene from 4
      methoxy-3-buten-2-one by cyclotrimerization in hot water in the absence of added
      acid or base.
AB  - Neat 1-phenyl- and 1-(p-tolyl)-2-propyn-1-ones (1 and 1', respectively) were
      heated in water without any additive at 150  degrees C for 2 h to give 1,3,5
      tribenzoyl- and 1,3,5-tri-(p-toluoyl)benzenes (2 and 2', respectively) in 74 and
      52% yields, respectively. The crossed reactions of 1 with the enolate of p
      toluoylacetaldehyde (3') and 1' with the enolate of benzoylacetaldehyde (3) were
      carried out to give unsymmetrically substituted 1-toluoyl-3,5-dibenzoylbenzene
      (Ph2Tol) and 1,3-ditoluoyl-5-benzoylbenzene (PhTol2), respectively, corroborating
      the previously proposed reaction mechanism in which 3 and 3' that are formed by
      rate-determining nucleophilic attack of HO(-) on 1 and 1' or its conjugate acids
      formed by subsequent protonation would serve as a common intermediate for the
      formation of 2, 2' and the acetophenone derivatives as byproducts. When 4-methoxy
      3-buten-2-one (4) was heated in hot pure water without any additive at 150 
      degrees C for 30 min, 1,3,5-triacetylbenzene (5) was obtained in an isolated
      yield of 77% just by removing water by filtering the crystalline product from the
      cooled reaction mixture. The reaction did not take place in the absence of water.
      Slow decompositions of 5 in water set in at the temperature of 300  degrees C for
      30 min.

PMID- 23126377
TI  - Strategic processing in long-term repetition priming in the lexical decision
      task.
AB  - In a lexical decision task, faster reaction times (RTs) for old than new items is
      taken as evidence for an implicit memory involvement in this task. In contrast,
      the present study shows the involvement of both implicit and explicit memory in
      repetition priming. We propose a dual route model, in which lexical decisions can
      be made using one of two parallel processing routes: a lexical route, in which
      the lexical properties of the stimulus are used to determine whether it is a word
      or not, and a strategic route that builds on the inherent correlation between
      "wordness" and "oldness" in the experiment. Eliminating the strategic route by
      removing this correlation diminishes the priming effect at the slow end of the RT
      distribution, but not at the fast end. This dissociation is interpreted as
      evidence for the involvement of both implicit and explicit memory in repetition
      priming.

PMID- 23126376
TI  - The family of DOF transcription factors in Brachypodium distachyon: phylogenetic
      comparison with rice and barley DOFs and expression profiling.
AB  - BACKGROUND: Transcription factors (TFs) are proteins that have played a central
      role both in evolution and in domestication, and are major regulators of
      development in living organisms. Plant genome sequences reveal that approximately
      7% of all genes encode putative TFs. The DOF (DNA binding with One Finger) TF
      family has been associated with vital processes exclusive to higher plants and to
      their close ancestors (algae, mosses and ferns). These are seed maturation and
      germination, light-mediated regulation, phytohormone and plant responses to
      biotic and abiotic stresses, etc. In Hordeum vulgare and Oryza sativa, 26 and 30
      different Dof genes, respectively, have been annotated. Brachypodium distachyon
      has been the first Pooideae grass to be sequenced and, due to its genomic,
      morphological and physiological characteristics, has emerged as the model system
      for temperate cereals, such as wheat and barley. RESULTS: Through searches in the
      B. distachyon genome, 27 Dof genes have been identified and a phylogenetic
      comparison with the Oryza sativa and the Hordeum vulgare DOFs has been performed.
      To explore the evolutionary relationship among these DOF proteins, a combined
      phylogenetic tree has been constructed with the Brachypodium DOFs and those from
      rice and barley. This phylogenetic analysis has classified the DOF proteins into
      four Major Cluster of Orthologous Groups (MCOGs). Using RT-qPCR analysis the
      expression profiles of the annotated BdDof genes across four organs (leaves,
      roots, spikes and seeds) has been investigated. These results have led to a
      classification of the BdDof genes into two groups, according to their expression
      levels. The genes highly or preferentially expressed in seeds have been subjected
      to a more detailed expression analysis (maturation, dry stage and germination).
      CONCLUSIONS: Comparison of the expression profiles of the Brachypodium Dof genes
      with the published functions of closely related DOF sequences from the cereal
      species considered here, deduced from the phylogenetic analysis, indicates that
      although the expression profile has been conserved in many of the putative
      orthologs, in some cases duplication followed by subsequent divergence may have
      occurred (neo-functionalization).

PMID- 23126378
TI  - High-throughput SISCAPA quantitation of peptides from human plasma digests by
      ultrafast, liquid chromatography-free mass spectrometry.
AB  - We investigated the utility of an SPE-MS/MS platform in combination with a
      modified SISCAPA workflow for chromatography-free MRM analysis of proteotypic
      peptides in digested human plasma. This combination of SISCAPA and SPE-MS/MS
      technology allows sensitive, MRM-based quantification of peptides from plasma
      digests with a sample cycle time of ~7 s, a 300-fold improvement over typical MRM
      analyses with analysis times of 30-40 min that use liquid chromatography upstream
      of MS. The optimized system includes capture and enrichment to near purity of
      target proteotypic peptides using rigorously selected, high affinity, antipeptide
      monoclonal antibodies and reduction of background peptides using a novel
      treatment of magnetic bead immunoadsorbents. Using this method, we have
      successfully quantitated LPS-binding protein and mesothelin (concentrations of
      ~5000 ng/mL and ~10 ng/mL, respectively) in human plasma. The method eliminates
      the need for upstream liquid-chromatography and can be multiplexed, thus
      facilitating quantitative analysis of proteins, including biomarkers, in large
      sample sets. The method is ideal for high-throughput biomarker validation after
      affinity enrichment and has the potential for applications in clinical
      laboratories.

PMID- 23126379
TI  - Correlation of lumbar medial branch neurotomy results with diagnostic medial
      branch block cutoff values to optimize therapeutic outcome.
AB  - OBJECTIVE: We sought an optimal medial branch block (MBB) cutoff value for both
      single and double MBB protocols that would best correlate with a positive outcome
      of medial branch neurotomy (MBN). OUTCOME MEASURES: We analyzed the percentage of
      subjective pain relief following MBB, confirmed by numerical rating scale (NRS)
      in aggravating positions before and 45 minutes after MBB. The percentage of
      overall pain relief following MBB was plotted against the following outcome
      variables: degree of subjective pain relief, duration of relief, patient
      satisfaction and activity level, no other doctor's visits, and reduction in
      medications use. RESULTS: Using the percent of pain relief post-MBB plotted in
      10% increments in the double-MBB group, patients reporting 70% or greater pain
      relief following MBB showed statistically favorable outcome for the following
      four criteria: percentage of pain relief, duration of relief, patient
      satisfaction, and pain medications reduction. In the single MBB group, patients
      reporting 80% or greater pain relief following MBB had favorable outcomes for
      improvement in activity level and patient satisfaction. CONCLUSIONS: The double
      MBB protocol better correlated with favorable MBN outcomes compared with a single
      MBB protocol. Using a double MBB protocol, a 70% cutoff value for reported
      subjective pain relief post-MBB best predicted overall outcome following MBN.
      Without a confirmatory MBB, an 80% cutoff value was the optimal value.

PMID- 23126380
TI  - Genetic variation in Norwegian piscine myocarditis virus in Atlantic salmon,
      Salmo salar L.
AB  - Cardiomyopathy syndrome (CMS) in Atlantic salmon, Salmo salar L., is a severe
      cardiac disease characterized by a necrotizing myocarditis involving the atrium
      and the spongious part of the ventricle. The disease is caused by piscine
      myocarditis virus (PMCV), a double-stranded RNA virus likely belonging to the
      family Totiviridae. The objective of this study was to evaluate the genetic
      variation in Norwegian PMCV isolates focusing on the putative structural proteins
      encoded by open reading frames (ORFs) 1 and 3. The virus isolates were sampled
      from a total of 36 farms along the Norwegian coastline. This study represents the
      first investigation of PMCV genome variation and shows that Norwegian isolates
      are highly similar, with the most divergent isolates sharing 98.6% nucleotide
      identity. Interestingly, amino acid sequence diversity within ORF3 is
      approximately threefold higher than for ORF1. While phylogenetic analysis based
      on concatenated nucleotide data covering ORF1 and ORF3 revealed four main
      clusters, the maximum sequence variation of 1.4% at the nucleotide level suggests
      that all Norwegian isolates belong to a single genogroup. Substantial sequence
      variation within farms was also observed, which may complicate future molecular
      epidemiological investigations. The genetic homogeneity among the Norwegian
      isolates might facilitate development of both diagnostic tools and an efficient
      vaccine against CMS in the future.

PMID- 23126381
TI  - Gradual scoliosis correction over time with shape-memory metal: a preliminary
      report of an experimental study.

PMID- 23126382
TI  - How the structural integrity of the matrix can influence the microstructural
      response of articular cartilage to compression.
AB  - This study investigated how the structural integrity of healthy, surface-removed
      (healthy), and degenerate matrices can modify the response of cartilage to
      compression. Six groups of specimens were loaded up to the onset of consolidation
      or at full consolidation (N = 30, 5 per group, respectively) and then
      subsequently chemically fixed to capture the deformed state of the tissues. Creep
      compression was applied through an 8 mm flat-ended indenter containing a 450 MUm
      diameter central pore, providing a region of high stress that also allowed the
      tissue samples to deform freely around the indenter pore during compression.
      Differential interference contrast microscopy was used in order to explore the
      microstructural responses of the tissues. The results demonstrated that
      superficial layer removal or tissue degeneration can reduce the observed
      deformation within the tissue region corresponding to the central pore of the
      loading indenter. Fibril crimping within the central pore matrix and matrix shear
      at the indenter edge regions are also reduced by both superficial layer removal
      and by tissue degeneration. These findings suggest that surface removal or tissue
      degeneration renders the matrix more susceptible to deformation and can also
      reduce the tissue's ability to transfer forces over a greater surface area and
      induce stress within the matrix.

PMID- 23126383
TI  - Aquaporin-4 knockout abolishes apomorphine-induced tardive dyskinesia following
      chronic treatment with neuroleptics.

PMID- 23126384
TI  - Tailored second-line therapy in asthmatic children with the Arg(16) genotype.
AB  - The Arg(16) beta(2) receptor genotype confers increased susceptibility to
      exacerbations in asthmatic children taking regular LABA (long-acting beta(2)
      agonists). We therefore evaluated using montelukast as an alternative to
      salmeterol as tailored second-line asthma controller therapy in children
      expressing this susceptible genotype. A total of 62 persistent asthmatic children
      with the homozygous Arg16 genotype were randomized to receive salmeterol (50 MUg,
      b.i.d.) or montelukast (5 or 10 mg, once daily) as an add-on to inhaled
      fluticasone for 1 year. School absences (the primary outcome) were reduced with
      montelukast compared with salmeterol {difference in score=-0.40 [95% CI
      (confidence interval), -0.22 to -0.58]; P=0.005}. Salbutamol use was also reduced
      with montelukast compared with salmeterol [difference in score=-0.47 (95% CI, 
      0.16 to -0.79); P<0.0001]. Greater improvements occurred in both symptom and
      quality of life scores with montelukast against salmeterol, whereas there was no
      difference in FEV(1) (forced expiratory volume in 1 s). In conclusion,
      montelukast may be suitable as tailored second-line controller therapy instead of
      salmeterol in asthmatic children expressing the susceptible Arg(16) genotype, a
      move towards a personalized medicine approach to management.

PMID- 23126385
TI  - Leucine-rich repeat kinase 2 inhibitors: a patent review (2006 - 2011).
AB  - INTRODUCTION: Leucine-rich repeat kinase 2 (LRRK2) has received considerable
      attention since the discovery of LRRK2 mutations in families with dominantly
      inherited Parkinson's disease (PD) in 2004. The missense mutation G2019S is the
      most common LRRK2 mutation and has been identified in both familial and sporadic
      PD cases. The G2019S mutation enhances kinase activity suggesting that LRRK2
      could be an attractive therapeutic target for PD and small-molecule ATP
      competitive LRRK2 kinase inhibitors are one way to investigate this possibility.
      AREAS COVERED: Currently, LRRK2 kinase inhibitors are being actively pursued by
      industry and academia. Herein, patents detailing the discovery of LRRK2 kinase
      inhibitors from 2006 through 2011 and the corresponding publications from 2006
      through July of 2012 are summarized. EXPERT OPINION: Wild-type and mutant forms
      of LRRK2 are currently being actively pursued as therapeutic targets for the
      potential treatment of PD. The increasing number of patent applications being
      filed for inhibitors of LRRK2 is a testament to this activity. Numerous distinct
      chemo-types have been reported as LRRK2 inhibitors with some demonstrating
      exceptional potency and selectivity for LRRK2 relative to other kinases. These
      compounds are being used as pharmacological 'tools' to elucidate the
      physiological and pathophysiological function of LRRK2 and it appears likely that
      some will be investigated for their potential therapeutic effects for the
      treatment of PD.

PMID- 23126386
TI  - Neuroprotective treatment of cerebral infarction: an experimental study.
AB  - We investigated the effect of the amniotic-derived peptide Plaferon-LB on
      cerebral tissue damage during photochemical insults in rats. Plaferon-LB (US
      patent number: 20070123467 A1) was extracted from the amniochorionic membrane of
      a human placenta and showed a relatively strong antihypoxic effect compared to
      other interferon. Thrombotic infarction was induced by photochemical illumination
      after intravenous injection of Rose Bengal. The infarct volume, cerebral tissue
      oxygen tension, cerebral blood flow, and capillary damage were measured in the
      following groups: untreated control rats, Plaferon-LB-alone rats, insult-alone
      rats, and insult in Plaferon-LB pretreated rats. The technique of electron
      paramagnetic resonance (EPR) spectroscopy was used to study free-radical
      metabolites in the blood and brain tissue ex vivo. Plaferon-LB alone had no
      effect on systemic blood pressure, cerebral blood flow, and reactive metabolites
      in the brains of intact animals. In the insult-alone group, a focal hemorrhage
      was observed in the ischemic area. The cerebral blood flow and tissue oxygen
      pressure declined to zero within an hour and remained at this level throughout
      the insult. The treatment with Plaferon-LB 0.5 hr before illumination resulted in
      a significant reduction of the median infarct size in the insult-alone group. The
      total length and percentage ratio of thrombotic vessels were significantly
      diminished in the infarct area. The intensity of Fe2+, Mn2+ -, Mo5+ 
      xanthinoxidase-containing complexes, and nitric oxide EPR signals was decreased,
      and the electron transport in the mitochondria was normalized. The results
      indicate a significant beneficial effect of Plaferon-LB on cerebral infarct,
      which is likely due to its antioxidative properties.

PMID- 23126387
TI  - Chemical plants: high-value molecules from essential oils.
AB  - As society faces a future of dwindling petrochemical supplies at increasing cost,
      much attention has been focused on methods to degrade biomass into renewable
      commodity-chemical building blocks. Reported here is a powerful complementary
      approach that amplifies the complexity of molecular structures present in plant
      materials. Essential-oil phenylpropenoids are transformed via acrylate cross
      metathesis into potent antioxidants that are widely used in perfumery and
      cosmetics, and in treating disorders associated with oxidative damage.

PMID- 23126388
TI  - Spillover of fish naivete from marine reserves.
AB  - Spillover of adult fish biomass is an expected benefit from no-take marine
      reserves to adjacent fisheries. Here, we show fisher-naive behaviour in reef
      fishes also spills over from marine reserves, potentially increasing access to
      fishery benefits by making fishes more susceptible to spearguns. The distance at
      which two targeted families of fishes began to flee a potential fisher [flight
      initiation distance (FID)] was lower inside reserves than in fished areas, and
      this reduction extended outside reserve boundaries. Reduced FID persisted further
      outside reserves than increases in fish biomass. This finding could help increase
      stakeholder support for marine reserves and improve current models of spillover
      by informing estimates for spatial changes in catchability. Behavioural changes
      of fish could help explain differences between underwater visual census and catch
      data in quantifying the spatial extent of spillover from marine reserves, and
      should be considered in the management of adjacent fisheries.

PMID- 23126389
TI  - For the love of labour.

PMID- 23126390
TI  - Advances in maternal fetal medicine practice.
AB  - Maternal fetal medicine (MFM) is a subspecialty of obstetrics that focuses on
      identified risk pregnancies. The role includes obstetric ultrasound for fetal
      assessment and diagnosis of anomalies, invasive prenatal diagnosis and management
      of pregnancies complicated by maternal medical disorders, multiple fetuses and
      the antenatal management of extreme prematurity. Skill specialisation within MFM
      includes fetal interventions such as fetal shunting procedures, intrauterine
      transfusion, fetoscopic laser photocoagulation of anastomotic vessels for twin to
      twin transfusion syndrome and ex utero intrapartum treatment. MFM specialists are
      actively involved in clinical and basic science research to improve maternal and
      neonatal outcomes. Most Australian MFM specialists are associated with
      metropolitan teaching hospitals. MFM sub-specialisation has reduced the impact of
      disability associated with aneuploidy, structural anomalies, multiple pregnancy
      and extreme prematurity. Management aims are to give families timely counselling,
      appropriate intervention, and optimisation of the time and location of delivery.
      The aim of this paper is to update the reader regarding current advances in MFM
      practices.

PMID- 23126391
TI  - Developmental dysplasia of the hip: controversies and current concepts.
AB  - Developmental dysplasia of the hip is an important but poorly understood disorder
      as evidenced by the vast amount of literature published to date on this topic.
      The precise definition of hip dysplasia is controversial and it encompasses a
      spectrum of abnormalities, rather than a single condition, which at one end
      overlap with normal hip maturation. We review the risk factors, clinical
      examination and radiological imaging of the hip in the infant and young child,
      the controversies of ultrasound screening for hip dysplasia and the current
      management, both operative and non-operative, of this condition according to
      patient age.

PMID- 23126392
TI  - Performance of the Australian Developmental Screening Test in a clinical setting.
AB  - AIMS: The study aims to assess the sensitivity and specificity of the Australian
      Developmental Screening Test (ADST) in a clinical setting in detecting
      developmental concerns that warrant further assessment or treatment. METHODS:  
      Clients referred to an inner Sydney Community Health Centre with developmental
      concerns were initially assessed using the ADST, followed within 12 weeks by an
      assessment using the Griffiths Mental Developmental Scales (GMDS) as the gold
      standard. RESULTS: Of the 65 eligible children, 46 (71%) had results indicating
      further assessment (42) or follow-up (4) was needed (using the criteria
      recommended in the ADST manual). However, of these only 21 (46%) had an abnormal
      GMDS. This gave a sensitivity of 95% but a specificity of only 52%. New threshold
      criteria for further assessment were developed and applied to three age groups.
      If children aged under 2 years are assessed using the standard ADST threshold,
      and children 2 years or older are assessed using the new ADST cut-off, then the
      tool has a sensitivity of 95%, a specificity of 82%, a positive likelihood ratio
      of 5.24 (95% CI 2.78, 9.88) and negative likelihood ratio of 0.06 (0.01, 0.40).
      CONCLUSIONS: Modified criteria for the ADST developed in this study showed good
      specificity and sensitivity for detection of developmental problems in this
      population, referred because of developmental concerns. Further testing to see if
      these new criteria perform well in a different population is now needed.

PMID- 23126393
TI  - Does prophylaxis with palivizumab reduce hospitalisation rates for respiratory
      syncytial-virus-related infection in cystic fibrosis children less than 2 years
      of age?

PMID- 23126394
TI  - Bilateral upper eyelid oedema.

PMID- 23126396
TI  - Mycotic pseudoaneurysm of the lingual artery: a rare complication of
      parapharyngeal abscess.

PMID- 23126397
TI  - Terra Firma Forme disease.

PMID- 23126398
TI  - Venlafaxine ingestion in a 4-year-old girl.

PMID- 23126399
TI  - Universal paediatric refugee health screening.

PMID- 23126401
TI  - A data-driven epidemiological prediction method for dengue outbreaks using local
      and remote sensing data.
AB  - BACKGROUND: Dengue is the most common arboviral disease of humans, with more than
      one third of the world's population at risk. Accurate prediction of dengue
      outbreaks may lead to public health interventions that mitigate the effect of the
      disease. Predicting infectious disease outbreaks is a challenging task; truly
      predictive methods are still in their infancy. METHODS: We describe a novel
      prediction method utilizing Fuzzy Association Rule Mining to extract
      relationships between clinical, meteorological, climatic, and socio-political
      data from Peru. These relationships are in the form of rules. The best set of
      rules is automatically chosen and forms a classifier. That classifier is then
      used to predict future dengue incidence as either HIGH (outbreak) or LOW (no
      outbreak), where these values are defined as being above and below the mean
      previous dengue incidence plus two standard deviations, respectively. RESULTS:
      Our automated method built three different fuzzy association rule models. Using
      the first two weekly models, we predicted dengue incidence three and four weeks
      in advance, respectively. The third prediction encompassed a four-week period,
      specifically four to seven weeks from time of prediction. Using previously unused
      test data for the period 4-7 weeks from time of prediction yielded a positive
      predictive value of 0.686, a negative predictive value of 0.976, a sensitivity of
      0.615, and a specificity of 0.982. CONCLUSIONS: We have developed a novel
      approach for dengue outbreak prediction. The method is general, could be extended
      for use in any geographical region, and has the potential to be extended to other
      environmentally influenced infections. The variables used in our method are
      widely available for most, if not all countries, enhancing the generalizability
      of our method.

PMID- 23126402
TI  - Enhanced human endothelial progenitor cell adhesion and differentiation by a
      bioinspired multifunctional nanomatrix.
AB  - Endothelial progenitor cell (EPC)-capturing techniques have led to revolutionary
      strategies that can improve the performance of cardiovascular implant devices and
      engineered tissues by enhancing re-endothelialization and angiogenesis. However,
      these strategies are limited by controversies regarding the phenotypic identities
      of EPCs as well as their inability to target and prevent the other afflictions
      associated with current therapies, namely, thrombosis and neointimal hyperplasia.
      Therefore, the goal of this study was to study the efficacy of a bioinspired
      multifunctional nanomatrix in recruiting and promoting the differentiation of
      EPCs toward an endothelial lineage. The bioinspired nanomatrix combines multiple
      components, including self-assembled peptide amphiphiles (PAs) that include cell
      adhesive ligands, nitric oxide (NO)-producing donors, and enzyme-mediated
      degradable sequences to achieve an endothelium-mimicking character. In this
      study, human peripheral blood mononuclear cells (PBMNCs) were isolated and
      cultured on the bioinspired multifunctional nanomatrix. Initial cell adhesion,
      lectin staining, acetylated low-density lipoprotein uptake, and expression of
      endothelial markers, including CD31, CD34, von Willebrand Factor, and VEGFR2,
      were analyzed. The results from this study indicate that the NO releasing
      bioinspired multifunctional nanomatrix promotes initial adhesion of EPCs when
      compared to control surfaces. The expression of endothelial markers is also
      increased on the bioinspired multifunctional nanomatrix, suggesting that it
      directs the differentiation of EPCs toward an endothelial phenotype. The
      bioinspired nanomatrix therefore provides a novel biomaterial-based platform for
      capturing as well as directing EPC behavior. Therefore, this study has the
      potential to positively impact the patency of cardiovascular devices such as
      stents and vascular grafts as well as enhanced angiogenesis for ischemic or
      engineered tissues.

PMID- 23126404
TI  - Hazards and respect: revisiting commentary, scholarship and argument in our field
      of persons.

PMID- 23126403
TI  - Shortening baroreflex delay in hypertrophic cardiomyopathy patients -- an unknown
      effect of beta-blockers.
AB  - AIMS: Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular
      hypertrophy and impaired diastolic and systolic function. Abnormal sympathetic
      parasympathetic balance is a potential stimulus for left ventricular hypertrophy
      in HCM patients. beta-Blockers are routinely used in HCM for their strong
      negative inotropic effect; however, these drugs also influence the sympathetic
      parasympathetic balance. This study aimed to determine the autonomic control of
      the cardiovascular system and the autonomic effects of beta-blockers in HCM
      patients treated or untreated with beta-blockers. METHODS: Among 51 HCM
      outpatients (18-70 years old; 29 men) there were 19 individuals with no
      medication and 32 subjects treated with a beta-blocker. Fourteen age- and gender
      matched (23-70 years old; nine men) healthy volunteers were enrolled in the
      control group. Continuous, non-invasive finger blood pressure was recorded during
      supine rest for 30 min. Autonomic regulation of the cardiovascular system was
      measured by heart rate variability and spontaneous baroreflex function (cross
      correlation sequence method). RESULTS: The mean pulse interval, time domain and
      spectral measures of heart rate variability and baroreflex sensitivity were
      comparable between HCM patients, treated or not with beta-blockers, and the
      control group. However, the delay of the baroreflex was significantly longer in
      HCM patients who were not treated with beta-blockers [2.0 (1.6-2.3) s] in
      comparison with HCM patients receiving beta-blockers [1.4 (1.1-1.8) s; P =
      0.0072] or control subjects [1.2 (0.8-1.8) s; P = 0.0025]. This delay did not
      differ between HCM patients treated with beta-blockers and the control group.
      CONCLUSIONS: Hypertrophic cardiomyopathy not treated with beta-blockers is
      accompanied by prolonged baroreflex delay. The use of beta-blockers normalizes
      this delay.

PMID- 23126405
TI  - Ion beam polishing for three-dimensional electron backscattered diffraction.
AB  - Serial sectioning by focused ion beam milling for three-dimensional electron
      backscatter diffraction (3D-EBSD) can create surface damage and amorphization in
      certain materials and consequently reduce the EBSD signal quality. Poor EBSD
      signal causes longer data acquisition time due to signal averaging and/or poor 3D
      EBSD data quality. In this work a low kV focused ion beam was successfully
      implemented to automatically polish surfaces during 3D-EBSD of La- and Nb-doped
      strontium titanate of volume 12.6 * 12.6 * 3.0 MUm. The key to achieving this
      technique is the combination of a defocused low kV high current ion beam and line
      scan milling. The line scan was used to restrict polishing to the sample surface
      and the ion beam was defocused to ensure the beam contacted the complete sample
      surface. In this study 1 min polishing time per slice increases total acquisition
      time by approximately 3.3% of normal 3D-EBSD mapping compared to a significant
      increase of indexing percentage and pattern quality. The polishing performance in
      this investigation is discussed, and two potential methods for further
      improvement are presented.

PMID- 23126406
TI  - Daily variation in natural disaster casualties: information flows, safety, and
      opportunity costs in tornado versus hurricane strikes.
AB  - Casualties from natural disasters may depend on the day of the week they strike.
      With data from the Spatial Hazard Events and Losses Database for the United
      States (SHELDUS), daily variation in hurricane and tornado casualties from 5,043
      tornado and 2,455 hurricane time/place events is analyzed. Hurricane forecasts
      provide at-risk populations with considerable lead time. Such lead time allows
      strategic behavior in choosing protective measures under hurricane threat;
      opportunity costs in terms of lost income are higher during weekdays than during
      weekends. On the other hand, the lead time provided by tornadoes is near zero;
      hence tornados generate no opportunity costs. Tornado casualties are related to
      risk information flows, which are higher during workdays than during leisure
      periods, and are related to sheltering-in-place opportunities, which are better
      in permanent buildings like businesses and schools. Consistent with theoretical
      expectations, random effects negative binomial regression results indicate that
      tornado events occurring on the workdays of Monday through Thursday are
      significantly less lethal than tornados that occur on weekends. In direct
      contrast, and also consistent with theory, the expected count of hurricane
      casualties increases significantly with weekday occurrences. The policy
      implications of observed daily variation in tornado and hurricane events are
      considered.

PMID- 23126407
TI  - Synthesis and characterization of mono-, di-, and tri-poly(ethylene glycol)
      chlorin e6 conjugates for the photokilling of human ovarian cancer cells.
AB  - PEGylated chlorin e(6) photosensitizers were synthesized with tri(ethylene
      glycol) attached at the ester bond(s) for a 1:1 conjugate at the 17(3)-position,
      a 2:1 conjugate at the 15(2)- and 17(3)-positions, and a 3:1 conjugate at the
      13(1)-, 15(2)-, and 17(3)-positions. These chlorin sensitizers were studied for
      hydrolytic stability and solubility, as well as ovarian OVCAR-5 cancer cell
      uptake, localization, and phototoxicity. Increasing numbers of the PEG groups in
      the mono-, di-, and tri-PEG chlorin conjugates increased the water solubility and
      sensitivity to hydrolysis and uptake into the ovarian cancer cells. The PEG
      chlorin conjugates accumulated in the cytoplasm and mitrochondria, but not in
      lysosomes. Higher phototoxicity was roughly correlated with higher numbers of PEG
      groups, with the tri-PEG chlorin conjugate showing the best overall ovarian
      cancer cell photokilling of the series. Singlet oxygen lifetimes, solvent
      deuteration, and the effects of additives azide ion and d-mannitol were examined
      to help clarify the photokilling mechanisms. A Type-II (singlet oxygen)
      photosensitized mechanism is suggested for the di- and tri-PEG chlorin
      conjugates; however, a more complicated process based in part on a Type-I
      (radicals or radical ions) mechanism is suggested for the parent chlorin e(6) and
      the mono-PEG chlorin conjugate.

PMID- 23126408
TI  - Coupling a detergent lysis/cleanup methodology with intact protein fractionation
      for enhanced proteome characterization.
AB  - The expanding use of surfactants for proteome sample preparations has prompted
      the need to systematically optimize the application and removal of these MS
      deleterious agents prior to proteome measurements. Here we compare four detergent
      cleanup methods (trichloroacetic acid (TCA) precipitation,
      chloroform/methanol/water (CMW) extraction, a commercial detergent removal spin
      column method (DRS) and filter-aided sample preparation (FASP)) to provide
      efficiency benchmarks with respect to protein, peptide, and spectral
      identifications in each case. Our results show that for protein-limited samples,
      FASP outperforms the other three cleanup methods, while at high protein amounts,
      all the methods are comparable. This information was used to investigate and
      contrast molecular weight-based fractionated with unfractionated lysates from
      three increasingly complex samples ( Escherichia coli  K-12, a five microbial
      isolate mixture, and a natural microbial community groundwater sample), all of
      which were prepared with an SDS-FASP approach. The additional fractionation step
      enhanced the number of protein identifications by 8% to 25% over the
      unfractionated approach across the three samples.

PMID- 23126410
TI  - Normal and pathological generosity.
AB  - This contribution delineates the formal and dynamic characteristics of
      generosity. It traces the origins of the trait of generosity to a complex
      interplay of hard-wired capacities for concern and altruism with gratifying
      experiences of early infancy and identifications with the generative parental
      qualities during later childhood and adolescence. Five pathological syndromes
      (namely, unrelenting generosity, begrudging generosity, fluctuating generosity,
      controlling generosity, and beguiling generosity) seem to exist in this realm.
      Technical implications of the notions outlined in this paper include: (i) having
      and maintaining an attitude of generosity towards the patient, (ii) listening and
      intervening with an attitude of generosity, (iii) recognizing and accepting the
      patient's healthy generosity, (iv) diagnosing and interpreting the patient's
      pathological generosity, (v) unmasking and interpreting defenses against
      generosity, and (vi) discerning and utilizing the countertransference to
      generosity. The paper also touches briefly upon miserliness, the opposite of
      generosity, and upon sociocultural dimensions of the matters involved.

PMID- 23126409
TI  - KNOX1 is expressed and epigenetically regulated during in vitro conditions in
      Agave spp.
AB  - BACKGROUND: The micropropagation is a powerful tool to scale up plants of
      economical and agronomical importance, enhancing crop productivity. However, a
      small but growing body of evidence suggests that epigenetic mechanisms, such as
      DNA methylation and histone modifications, can be affected under the in vitro
      conditions characteristic of micropropagation. Here, we tested whether the
      adaptation to different in vitro systems (Magenta boxes and Bioreactors) modified
      epigenetically different clones of Agave fourcroydes and A. angustifolia.
      Furthermore, we assessed whether these epigenetic changes affect the regulatory
      expression of KNOTTED1-like HOMEOBOX (KNOX) transcription factors. RESULTS: To
      gain a better understanding of epigenetic changes during in vitro and ex vitro
      conditions in Agave fourcroydes and A. angustifolia, we analyzed global DNA
      methylation, as well as different histone modification marks, in two different
      systems: semisolid in Magenta boxes (M) and temporary immersion in modular
      Bioreactors (B). No significant difference was found in DNA methylation in A.
      fourcroydes grown in either M or B. However, when A. fourcroydes was compared
      with A. angustifolia, there was a two-fold difference in DNA methylation between
      the species, independent of the in vitro system used. Furthermore, we detected an
      absence or a low amount of the repressive mark H3K9me2 in ex vitro conditions in
      plants that were cultured earlier either in M or B. Moreover, the expression of
      AtqKNOX1 and AtqKNOX2, on A. fourcroydes and A. angustifolia clones, is affected
      during in vitro conditions. Therefore, we used Chromatin ImmunoPrecipitation
      (ChIP) to know whether these genes were epigenetically regulated. In the case of
      AtqKNOX1, the H3K4me3 and H3K9me2 were affected during in vitro conditions in
      comparison with AtqKNOX2. CONCLUSIONS: Agave clones plants with higher DNA
      methylation during in vitro conditions were better adapted to ex vitro
      conditions. In addition, A. fourcroydes and A. angustifolia clones displayed
      differential expression of the KNOX1 gene during in vitro conditions, which is
      epigenetically regulated by the H3K4me3 and H3K9me2 marks. The finding of an
      epigenetic regulation in key developmental genes will make it important in future
      studies to identify factors that help to find climate-resistant micropropagated
      plants.

PMID- 23126411
TI  - The Creative Transformation of Trauma: Marcel Proust's in search of lost time.
AB  - Hidden childhood trauma beneath poignant memories is a central aspect of In
      Search of Lost Time. Marcel Proust's magnum opus may be psychoanalytically
      understood as an extraordinary literary transformation of severe trauma and
      associated unconscious confiicts. Proust's nearly fatal childhood asthma and
      concomitant medical mistreatment contributed to an intense ambivalent bond and
      bondage with his mother, replicated in the ambivalent relationships depicted in
      his novel. The retrieved and re-created past is relived in the novel's fantasy
      playground of time and space. Proust's intuitive grasp of signiflcant aspects of
      time, memory, trauma, and transference was consistent with psychoanalytic
      thought. In the vast novel, the narcissistic mortiflcation and losses of the
      protagonist are mourned, worked through, and partially redeemed. I interpret the
      famed joyous tasting of the madeleine in tea as an artfully disguised, temporally
      displaced, and affective reversal of life-threatening trauma. This article probes
      the role of Proust's intractable asthma in his breathless journey to ego mastery
      and timeless creativity.

PMID- 23126412
TI  - The emergence of athleticism and participation in athletics: a proposed line of
      development.
AB  - A developmental line focusing on interest and participation in sports is
      proposed. The changing role of the body in the development of the ego is
      considered. The body as an early source of pleasure eventually becomes the site
      of a source of primordial competence, and by the latency phase, full-fiedged
      competence can be generated by the ego's control of the body in space.
      Participation in sports and acquisition of athletic skills can follow.

PMID- 23126413
TI  - How the analytic process is captured and absorbed into the familiar, the feared,
      and the desired.
AB  - In their transference efforts to maintain psychic equilibrium (Joseph, 1989),
      some patients will do their best to convert their analysts into familiar,
      dreaded, or desired internal objects which they then react to or relate to. The
      interpersonal, interactional, and intrapsychic pull for the absorption and
      utilization of the analyst into a predesigned and pathologically limited figure
      creates countertransference struggles and phases of enactment that can go
      unnoticed, denied, or justified. Even when analysts maintain their analytic
      balance, the patient can manipulate, mishear, and transform words, actions, and
      intentions into very specific archaic objects or part objects.   Case material is
      used to illustrate the way in which patients attempt to turn the analytic process
      and the therapeutic relationship into an acting out of wished for or painfully
      familiar self and object interactions. This method of subsuming the analytic
      method can be quite subtle, or it can be very obvious but still extremely
      difficult to shift, interpret, or recover from. Indeed, the analyst can easily be
      drawn into this perversion of analytic procedure and end up participating in
      various enactments.   With such patients, the nature of the unconscious fantasies
      projected into the transference matrix and the intensity of the patient's object
      relational conflicts almost guarantee some degree of ongoing countertransference
      acting out. So, the ongoing and repetitive interpretive style needed with such
      patients is both helpful and healing as well as often becoming a contribution to
      the fundamental pathology the patient repeats in the clinical setting. Although
      the transference dynamic being examined could be understood from a number of
      theoretical perspectives, the author focuses on the Kleinian psychoanalytic
      method.

PMID- 23126414
TI  - Leader psychobiography and social movement studies: a Kleinian case study of
      Bruce Gagnon and the outer space protection movement.
AB  - This paper begins by highlighting the necessity of combining sociological and
      psychoanalytic approaches in the study of social movements, but acknowledges that
      psychobiographical studies of prominent movement leaders sit uneasily within the
      sociological tradition. The author attempts to illustrate that leader
      psychobiography can make a contribution to understanding social movements,
      however, provided it offers a way into understanding broader psychosocial issues
      within the movement. This is achieved through a psychobiographical portrait of
      Bruce Gagnon, a leader within the outer space protection movement. The author
      argues for the central importance of both paranoid-schizoid and depressive
      mechanisms throughout Gagnon's activist career. These eventually came to underpin
      Gagnon's commitment to protecting outer space as a Kleinian "good object." The
      paper concludes by suggesting how Gagnon's psychobiography might be instructive
      in attempts to understand the wider movement, utilizing Erikson's model for
      psychohistorical study as a framework.

PMID- 23126417
TI  - A new submaximal cycle ergometer test for prediction of VO2max.
AB  - Maximal oxygen uptake (VO2max) is an important, independent predictor of
      cardiovascular health and mortality. Despite this, it is rarely measured in
      clinical practice. The aim of this study was to create and evaluate a submaximal
      cycle ergometry test based on change in heart rate (HR) between a lower standard
      work rate and an individually chosen higher work rate. In a mixed population (n =
      143) with regard to sex (55% women), age (21-65 years), and activity status
      (inactive to highly active), a model included change in HR per unit change in
      power, sex, and age for the best estimate of VO2max. The association between
      estimated and observed VO2max for the mixed sample was r = 0.91, standard error
      of estimate = 0.302 L/min, and mean measured VO2max = 3.23 L/min. The
      corresponding coefficient of variation was 9.3%, a significantly improved
      precision compared with one of the most commonly used submaximal exercise tests,
      the Astrand test, which in the present study was estimated to be 18.1%. Test
      retest reliability analysis over 1 week revealed no mean difference in the
      estimated VO2max (-0.02 L/min, 95% confidence interval: -0.07-0.03). The new test
      is low-risk, easily administered, and valid for a wide capacity range, and is
      therefore suitable in situations as health evaluations in the general population.

PMID- 23126418
TI  - Acid-base site detection and mapping on solid surfaces by Kelvin force microscopy
      (KFM).
AB  - Electrostatic potential at the surface of acidic or basic solids changes under
      higher relative humidity (RH), as determined by using Kelvin force microscopy
      (KFM). The potential on acid surfaces becomes more negative as the water vapor
      pressure increases, while it becomes more positive on basic solids. These results
      verify the following hypothesis: OH(-) or H(+) ions associated with atmospheric
      water ion clusters are selectively adsorbed on solid surfaces, depending on the
      respective Bronsted acid or base character. Therefore, Kelvin microscopy, under
      variable humidity, is a rigorous but convenient alternative to determine the acid
      base character of solid surfaces, with a great advantage: it uses only one
      amphoteric and simple reagent to determine both the acid and base sites.
      Moreover, this technique provides information on the spatial distribution of acid
      base sites, which is currently inaccessible to any other method.

PMID- 23126420
TI  - Interprofessional collaborative practice: a deconstruction.
AB  - This paper uses (and perhaps abuses) deconstruction to revisit the meanings of
      collaboration and practice. We start with a description of deconstruction itself,
      as espoused by Jacques Derrida, and then move onto challenging the notion that
      words, such as collaboration, can have fixed meanings. And, in the spirit of
      Derrida, "I can foresee the impatience of the bad reader: this is the way I name
      or accuse the fearful reader, the reader in a hurry to be determined, decided
      upon deciding (in order to annul, in other words to bring back to oneself, one
      has to wish to know in advance what to expect...)" (Derrida, 1987, p. 4--original
      italics), we move straight into the text.

PMID- 23126421
TI  - Social capital and relational coordination in outpatient clinics: an
      interprofessional analysis.
AB  - Coordination is a vital component in healthcare provision and teamwork.
      Relational coordination (RC) represents a type of informal coordination
      reinforced by communication and supportive relationships. It is an important
      concept in the study of interprofessional team performance and is associated with
      improved patient care outcomes. However, little is known about the specific
      relational characteristics that contribute to higher levels of RC. This study
      examined the association between social capital (resources embedded within
      relationships) and RC in outpatient clinics. RC was hypothesized to be predicted
      by social capital. In addition, social capital was hypothesized to be predicted
      by team tenure, and RC was hypothesized to be predicted by formal coordination
      mechanisms. A cross-sectional design was used to survey a random sample of 342
      physicians and nurses from outpatient clinics. Study variables were measured
      using previously validated instruments with acceptable levels of reliability and
      validity. Structural equation modeling was used for hypothesis testing. Final
      analysis revealed a good fit of data to the hypothesized model (comparative fit
      index = 0.966; standardized root mean square residual = 0.0316). Results
      suggested that social capital predicted both factors of RC (b = 0.70 and 0.81, p
      < 0.001) and team tenure predicted social capital (b = 0.13, p < 0.05). Also, the
      association between team tenure and RC (b = 0.09, p < 0.05) was found to be
      partially mediated by social capital. Findings of this study suggest that
      characteristics within relational ties are predictive of informal coordination.
      The strength and pattern of these associations provide a better understanding in
      how relationships may facilitate interprofessional teamwork.

PMID- 23126422
TI  - 2-Amino-4-arylthiazole compounds as TRPA1 antagonists (WO 2012085662): a patent
      evaluation.
AB  - The patent claims 2-amino-4-arylthiazole derivative compounds as inhibitors of
      the TRPA1 (transient receptor potential ankyrin, member 1) receptor. These
      compounds are potent antagonists on the basis of the results of in vitro assays,
      and are expected to be useful for treating conditions and disorders associated
      with TRPA1 function such as pain, chronic pain, neuropathic pain, rheumatoid
      arthritic pain, osteoarthritic pain, diabetic neuropathy and inflammatory
      disorders.

PMID- 23126423
TI  - Consistent condom use increases spontaneous regression in high-risk non-HPV16 but
      not in HPV16 CIN2-3 lesions, a prospective population-based cohort study.
AB  - BACKGROUND: The major cause of cervical intraepithelial neoplasia (CIN) is
      persistent infection with human papillomavirus (HPV). Most CIN grade 2 and 3
      lesions are treated with cone excision, although a substantial proportion (6-50%)
      of CIN2-3 lesions will regresses spontaneously. Predictors for regression of CIN2
      3 are desirable in order to reduce this overtreatment. METHODS: In this
      prospective cohort study, 145 consecutive women with first-time onset CIN2-3 in
      colposcopy-directed biopsies and standardized biopsy-cone excision interval were
      included. The genotype of the high-risk human papillomaviruses (=hrHPV) and
      clinical factors including sexual behaviour, parity, contraception and smoking
      were assessed. Patients were divided into two groups according to lesions
      containing HPV16 (hrHPV16+) and high-risk non-HPV16 (hrHPV16-) genotypes.
      RESULTS: Women whose partners consistently used condoms showed a significantly
      higher regression rate than women using other types of contraception (53% versus
      13%, p<0.0001). However, this effect was only seen in hrHPV16- patients (73%
      regression rate versus 13%, p<0.0001). HrHPV16+ patients had a significantly
      higher number of sexual partners and more current smokers compared to hrHPV16-
      patients. The regression rate was not significantly different in CIN2-3 lesions
      containing HPV16 (hrHPV16+) versus hrHPV16- genotypes. CONCLUSIONS: Heterogeneity
      among hrHPV genotypes excists. HPV-genotype analyses can identify women who
      significantly increase their chance of regression by consistent condom use.

PMID- 23126424
TI  - Recent advances in laparoscopic surgery.
AB  - Laparoscopic surgery has been widely adopted and new technical innovation,
      procedures and evidence based knowledge are persistently emerging. This review
      documents recent major advancements in laparoscopic surgery. A PubMed search was
      made in order to identify recent advances in this field. We reviewed the recent
      data on randomized trials in this field as well as papers of systematic review.
      Laparoscopic cholecystectomy is the most frequently performed procedure, followed
      by laparoscopic bariatric surgery. Although bile duct injuries are relatively
      uncommon (0.15%-0.6%), intraoperative cholangiography still plays a role in
      reducing the cost of litigation. Laparoscopic bariatric surgery is the most
      commonly performed laparoscopic gastrointestinal surgery in the USA, and
      laparoscopic Nissen fundoplication is the treatment of choice for intractable
      gastroesophageal reflux disease. Recent randomized trials have demonstrated that
      laparoscopic gastric and colorectal cancer resection are safe and oncologically
      correct procedures. Laparoscopic surgery has also been widely developed in
      hepatic, pancreatic, gynecological and urological surgery. Recently, SILS and
      robotic surgery have penetrated all specialties of abdominal surgery. However,
      evidence-based medicine has failed to show major advantages in SILS, and the
      disadvantage of robotic surgery is the high costs related to purchase and
      maintenance of technology. Laparoscopic surgery has become well developed in
      recent decades and is the choice of treatment in abdominal surgery. Recently
      developed SILS techniques and robotic surgery are promising but their benefits
      remain to be determined.

PMID- 23126425
TI  - Insulin-like growth factor-binding protein-6 and cancer.
AB  - The IGF (insulin-like growth factor) system is essential for physiological growth
      and it is also implicated in a number of diseases including cancer. IGF activity
      is modulated by a family of high-affinity IGF-binding proteins, and IGFBP-6 is
      distinctive because of its marked binding preference for IGF-II over IGF-I. A
      principal role for IGFBP-6 is inhibition of IGF-II actions, but recent studies
      have indicated that IGFBP-6 also has IGF-independent effects, including
      inhibition of angiogenesis and promotion of cancer cell migration. The present
      review briefly summarizes the IGF system in physiology and disease before
      focusing on recent studies on the regulation and actions of IGFBP-6, and its
      potential roles in cancer cells. Given the widespread interest in IGF inhibition
      in cancer therapeutics, increasing our understanding of the mechanisms underlying
      the actions of the IGF ligands, receptors and binding proteins, including IGFBP
      6, will enhance our ability to develop optimal treatments that can be targeted to
      the most appropriate patients.

PMID- 23126426
TI  - The defence of body weight: a physiological basis for weight regain after weight
      loss.
AB  - Although weight loss can usually be achieved by restricting food intake, the
      majority of dieters regain weight over the long-term. In the hypothalamus,
      hormonal signals from the gastrointestinal tract, adipose tissue and other
      peripheral sites are integrated to influence appetite and energy expenditure.
      Diet-induced weight loss is accompanied by several physiological changes which
      encourage weight regain, including alterations in energy expenditure, substrate
      metabolism and hormone pathways involved in appetite regulation, many of which
      persist beyond the initial weight loss period. Safe effective long-term
      strategies to overcome these physiological changes are needed to help facilitate
      maintenance of weight loss. The present review, which focuses on data from human
      studies, begins with an outline of body weight regulation to provide the context
      for the subsequent discussion of short- and long-term physiological changes which
      accompany diet-induced weight loss.

PMID- 23126427
TI  - Role of the TGF-beta/BMP-7/Smad pathways in renal diseases.
AB  - TGF-beta (transforming growth factor-beta) and BMP-7 (bone morphogenetic protein
      7), two key members in the TGF-beta superfamily, play important but diverse roles
      in CKDs (chronic kidney diseases). Both TGF-beta and BMP-7 share similar
      downstream Smad signalling pathways, but counter-regulate each other to maintain
      the balance of their biological activities. During renal injury in CKDs, this
      balance is significantly altered because TGF-beta signalling is up-regulated by
      inducing TGF-beta1 and activating Smad3, whereas BMP-7 and its downstream
      Smad1/5/8 are down-regulated. In the context of renal fibrosis, Smad3 is
      pathogenic, whereas Smad2 and Smad7 are renoprotective. However, this counter
      balancing mechanism is also altered because TGF-beta1 induces Smurf2, a ubiquitin
      E3-ligase, to target Smad7 as well as Smad2 for degradation. Thus overexpression
      of renal Smad7 restores the balance of TGF-beta/Smad signalling and has
      therapeutic effect on CKDs. Recent studies also found that Smad3 mediated renal
      fibrosis by up-regulating miR-21 (where miR represents microRNA) and miR-192, but
      down-regulating miR-29 and miR-200 families. Therefore restoring miR-29/miR-200
      or suppressing miR-21/miR-192 is able to treat progressive renal fibrosis.
      Furthermore, activation of TGF-beta/Smad signalling inhibits renal BMP-7
      expression and BMP/Smad signalling. On the other hand, overexpression of renal
      BMP-7 is capable of inhibiting TGF-beta/Smad3 signalling and protects the kidney
      from TGF-beta-mediated renal injury. This counter-regulation not only expands our
      understanding of the causes of renal injury, but also suggests the therapeutic
      potential by targeting TGF-beta/Smad signalling or restoring BMP-7 in CKDs. Taken
      together, the current understanding of the distinct roles and mechanisms of TGF
      beta and BMP-7 in CKDs implies that targeting the TGF-beta/Smad pathway or
      restoring BMP-7 signalling may represent novel and effective therapies for CKDs.

PMID- 23126429
TI  - Changes of serum myeloperoxidase and nitric oxide in the early stage of
      Edwardsiella ictaluri infection in channel catfish, Ictalurus punctatus
      (Rafinesque).

PMID- 23126428
TI  - Rural African American parents' knowledge and decisions about human
      papillomavirus vaccination.
AB  - PURPOSE: To identify predictors of human papillomavirus (HPV) vaccination among
      rural African American families. DESIGN: Cross-sectional descriptive study in
      schools in three rural counties in southeastern United States. The sample
      consisted of African American parents or caregivers with children 9 to 13 years
      of age who attended elementary or middle school in 2010-2011. METHODS: Using an
      anonymous, 26-item survey, we collected descriptive data during parent-teacher
      events from African American parents with children in elementary or middle
      school. The main outcome was measured as a response of "yes" to the statement "I
      have or will vaccinate my child with the HPV vaccine." In addition, composite
      scores of knowledge and positive attitudes and beliefs were compared. No
      interventions were conducted. FINDINGS: We identified predictors of HPV
      vaccination and found that religious affiliation had a correlation with
      vaccinating or planning to vaccinate a child. CONCLUSIONS: Results indicate a
      need for further research on the role of local culture, including religion and
      faith, in rural African Americans' decisions about giving their children the HPV
      vaccination. CLINICAL RELEVANCE: This study emphasizes the importance of
      understanding rural African American parents' knowledge, attitudes, and spiritual
      beliefs when designing health education programs and public health interventions
      to increase HPV vaccination uptake among African American boys and girls living
      in rural areas.

PMID- 23126430
TI  - Reversible and oriented immobilization of ferrocene-modified proteins.
AB  - Adopting supramolecular chemistry for immobilization of proteins is an attractive
      strategy that entails reversibility and responsiveness to stimuli. The reversible
      and oriented immobilization and micropatterning of ferrocene-tagged yellow
      fluorescent proteins (Fc-YFPs) onto beta-cyclodextrin (betaCD) molecular
      printboards was characterized using surface plasmon resonance (SPR) spectroscopy
      and fluorescence microscopy in combination with electrochemistry. The proteins
      were assembled on the surface through the specific supramolecular host-guest
      interaction between betaCD and ferrocene. Application of a dynamic covalent
      disulfide lock between two YFP proteins resulted in a switch from monovalent to
      divalent ferrocene interactions with the betaCD surface, yielding a more stable
      protein immobilization. The SPR titration data for the protein immobilization
      were fitted to a 1:1 Langmuir-type model, yielding K(LM) = 2.5 * 10(5) M(-1) and
      K(i,s) = 1.2 * 10(3) M(-1), which compares favorably to the intrinsic binding
      constant presented in the literature for the monovalent interaction of ferrocene
      with betaCD self-assembled monolayers. In addition, the SPR binding experiments
      were qualitatively simulated, confirming the binding of Fc-YFP in both divalent
      and monovalent fashion to the betaCD monolayers. The Fc-YFPs could be patterned
      on betaCD surfaces in uniform monolayers, as revealed using fluorescence
      microscopy and atomic force microscopy measurements. Both fluorescence microscopy
      imaging and SPR measurements were carried out with the in situ capability to
      perform cyclic voltammetry and chronoamperometry. These studies emphasize the
      repetitive desorption and adsorption of the ferrocene-tagged proteins from the
      betaCD surface upon electrochemical oxidation and reduction, respectively.

PMID- 23126431
TI  - Stakeholder perceptions of a nurse led walk-in centre.
AB  - BACKGROUND: As many countries face primary care medical workforce shortages and
      find it difficult to provide timely and affordable care they seek to find new
      ways of delivering first point of contact health care through developing new
      service models. In common with other areas of rural and regional Australia, the
      Australian Capital Territory (ACT) is currently experiencing a general
      practitioner (GP) workforce shortage which impacts significantly on the ability
      of patients to access GP led primary care services. The introduction of a nurse
      led primary care Walk-in Centre in the ACT aimed to fulfill an unmet health care
      need in the community and meet projected demand for health care services as well
      as relieve pressure on the hospital system. Stakeholders have the potential to
      influence health service planning and policy, to advise on the potential of
      services to meet population health needs and to assess how acceptable health
      service innovation is to key stakeholder groups. This study aimed to ascertain
      the views of key stakeholders about the Walk-in Centre. METHODS: Stakeholders
      were purposively selected through the identification of individuals and
      organisations which had organisational or professional contact with the Walk-in
      Centre. Semi structured interviews around key themes were conducted with
      seventeen stakeholders. RESULTS: Stakeholders were generally supportive of the
      Walk-in Centre but identified key areas which they considered needed to be
      addressed. These included the service's systems, full utilisation of the nurse
      practitioner role and adequate education and training. It was also suggested that
      a doctor could be available to the Centre as a source of referral for patients
      who fall outside the nurses' scope of practice. The location of the Centre was
      seen to impact on patient flows to the Emergency Department. CONCLUSION: Nurse
      led Walk-in Centres are one response to addressing primary health care medical
      workforce shortages. Whilst some stakeholders have reservations about the model
      others are supportive and see the potential the model has to provide accessible
      primary health care. Any further developments of nurse-led Walk-in Centres need
      to take into account the views of key stakeholders so as to ensure that the model
      is acceptable and sustainable.

PMID- 23126432
TI  - Segmenting time-lapse phase contrast images of adjacent NIH 3T3 cells.
AB  - We present a new method for segmenting phase contrast images of NIH 3T3
      fibroblast cells that is accurate even when cells are physically in contact with
      each other. The problem of segmentation, when cells are in contact, poses a
      challenge to the accurate automation of cell counting, tracking and lineage
      modelling in cell biology. The segmentation method presented in this paper
      consists of (1) background reconstruction to obtain noise-free foreground pixels
      and (2) incorporation of biological insight about dividing and nondividing cells
      into the segmentation process to achieve reliable separation of foreground pixels
      defined as pixels associated with individual cells. The segmentation results for
      a time-lapse image stack were compared against 238 manually segmented images
      (8219 cells) provided by experts, which we consider as reference data. We chose
      two metrics to measure the accuracy of segmentation: the 'Adjusted Rand Index'
      which compares similarities at a pixel level between masks resulting from manual
      and automated segmentation, and the 'Number of Cells per Field' (NCF) which
      compares the number of cells identified in the field by manual versus automated
      analysis. Our results show that the automated segmentation compared to manual
      segmentation has an average adjusted rand index of 0.96 (1 being a perfect
      match), with a standard deviation of 0.03, and an average difference of the two
      numbers of cells per field equal to 5.39% with a standard deviation of 4.6%.

PMID- 23126433
TI  - Sexual violence and genital injury: the physiology of HIV transmission risk.

PMID- 23126434
TI  - The nature of "internal sensations" of higher brain functions may be derived from
      the design rules for artificial machines that can produce them.
AB  - Modeling various neuronal functions in search of emergent properties may achieve
      success when the gold standard of replicating the models in physical systems
      starts exhibiting some of these properties. Since very large number of functions
      can be modeled and need testing, we suggest an alternate method of examining
      higher brain functions: seeing them as internal sensations formed from their
      hypothetical basic units. Here, we explain the need to replicate the natural
      mechanism using electronic circuits, discuss some of the technical aspects and
      introduce some concepts for searching for properties of internal sensations
      evolving from them.

PMID- 23126435
TI  - Pyoverdine biosynthesis and secretion in Pseudomonas aeruginosa: implications for
      metal homeostasis.
AB  - Pyoverdines are siderophores produced by fluorescent Pseudomonads to acquire
      iron. At least 60 different pyoverdines produced by diverse strains have been
      chemically characterized. They all consist of a dihydroquinoline-type chromophore
      linked to a peptide. These peptides are of various lengths and the sequences are
      strain specific. Pyoverdine biosynthesis in Pseudomonas aeruginosa and
      fluorescent Pseudomonads is a complex process involving at least 12 different
      proteins, starting in the cytoplasm and ending in the periplasm. The cellular
      localization of pyoverdine precursors was recently shown to be consistent with
      their biosynthetic enzymes. In the cytoplasm, pyoverdine appears to be assembled
      at the inner membrane and particularly at the old cell pole of the bacterium.
      Mature pyoverdine is uniformly distributed throughout the periplasm, like the
      periplasmic enzyme PvdQ. Secretion of pyoverdine involves a recently identified
      ATP-dependent efflux pump, PvdRT-OpmQ. This efflux system does not only secrete
      newly synthesized pyoverdine but also pyoverdine that already transported iron
      into the bacterial periplasm and any pyoverdine-metal complex other than ferri
      pyoverdine present in the periplasm. This review considers how these new insights
      into pyoverdine biosynthesis and secretion contribute to our understanding of the
      role of pyoverdine in iron and metal homeostasis in fluorescent Pseudomonads.

PMID- 23126436
TI  - A quantitative assessment of the prion risk associated with wastewater from
      carcass-handling facilities.
AB  - Wastewater from facilities processing livestock that may harbor transmissible
      spongiform encephalopathies (TSEs) infectivity is permitted under license for
      application to land where susceptible livestock may have access. Several previous
      risk assessments have investigated the risk of bovine spongiform encephalopathy
      (BSE) associated with wastewater effluents; however, the risk of exposure to
      classical scrapie and atypical scrapie has not been assessed. With the prevalence
      of certain TSEs (BSE in cattle and classical scrapie in sheep) steadily in
      decline, and with considerable changes in the structure of carcass-processing
      industries in Great Britain, a reappraisal of the TSE risk posed by wastewater is
      required. Our results indicate that the predicted number of new TSE infections
      arising from the spreading of wastewater on pasture over one year would be low,
      with a mean of one infection every 1,000 years for BSE in cattle (769, 555,556),
      and one infection every 30 years (16, 2,500), and 33 years (16, 3,333) for
      classical and atypical scrapie, respectively. It is assumed that the values and
      assumptions used in this risk assessment remain constant. For BSE in cattle the
      main contributors are abattoir and rendering effluent, contributing 35% and 22%
      of the total number of new BSE infections. For TSEs in sheep, effluent from small
      incinerators and rendering plants are the major contributors (on average 32% and
      31% of the total number of new classical scrapie and atypical scrapie
      infections). This is a reflection of the volume of carcass material and Category
      1 material flow through such facilities. 

PMID- 23126438
TI  - Media multitasking is associated with symptoms of depression and social anxiety.
AB  - We investigated whether multitasking with media was a unique predictor of
      depression and social anxiety symptoms. Participants (N=318) completed measures
      of their media use, personality characteristics, depression, and social anxiety.
      Regression analyses revealed that increased media multitasking was associated
      with higher depression and social anxiety symptoms, even after controlling for
      overall media use and the personality traits of neuroticism and extraversion. The
      unique association between media multitasking and these measures of psychosocial
      dysfunction suggests that the growing trend of multitasking with media may
      represent a unique risk factor for mental health problems related to mood and
      anxiety. Further, the results strongly suggest that future research investigating
      the impact of media use on mental health needs to consider the role that
      multitasking with media plays in the relationship.

PMID- 23126437
TI  - Ketorolac reduces spinal astrocytic activation and PAR1 expression associated
      with attenuation of pain after facet joint injury.
AB  - Chronic neck pain affects up to 70% of persons, with the facet joint being the
      most common source. Intra-articular injection of the non-steroidal anti
      inflammatory drug ketorolac reduces post-operative joint-mediated pain; however,
      the mechanism of its attenuation of facet-mediated pain has not been evaluated.
      Protease-activated receptor-1 (PAR1) has differential roles in pain maintenance
      depending on the type and location of painful injury. This study investigated if
      the timing of intra-articular ketorolac injection after painful cervical facet
      injury affects behavioral hypersensitivity by modulating spinal astrocyte
      activation and/or PAR1 expression. Rats underwent a painful joint distraction and
      received an injection of ketorolac either immediately or 1 day later. Separate
      control groups included injured rats with a vehicle injection at day 1 and sham
      operated rats. Forepaw mechanical allodynia was measured for 7 days, and spinal
      cord tissue was immunolabeled for glial fibrillary acidic protein (GFAP) and PAR1
      expression in the dorsal horn on day 7. Ketorolac administered on day 1 after
      injury significantly reduced allodynia (p=0.0006) to sham levels, whereas
      injection immediately after the injury had no effect compared with vehicle.
      Spinal astrocytic activation followed behavioral responses and was significantly
      decreased (p=0.009) only for ketorolac given at day 1. Spinal PAR1 (p=0.0025) and
      astrocytic PAR1 (p=0.012) were significantly increased after injury. Paralleling
      behavioral data, astrocytic PAR1 was returned to levels in sham only when
      ketorolac was administered on day 1. Yet, spinal PAR1 was significantly reduced
      (p<0.0001) by ketorolac independent of timing. Spinal astrocyte expression of
      PAR1 appears to be associated with the maintenance of facet-mediated pain.

PMID- 23126439
TI  - Homozygous c.649dupC mutation in PRRT2 worsens the BFIS/PKD phenotype with mental
      retardation, episodic ataxia, and absences.
AB  - Heterozygous mutations of PRRT2, which encodes proline-rich transmembrane protein
      2, are associated with heterogeneous phenotypes including benign familial
      infantile seizures (BFIS), or familial paroxysmal kinesigenic dystonia (PKD). We
      report a consanguineous Italian family with BFIS/PKD phenotype that contained 14
      living members with 6 affected individuals (four men, ranging in age from 6-44
      years). We identified the reported c.649dupC (p.Arg217ProfsX8) mutation of PRRT2
      gene that cosegregated with the disease and was not observed in 100 controls of
      matched ancestry. Four patients with BFIS phenotype were heterozygous for this
      mutation, including the consanguineous parents of the two affected brothers with
      more severe phenotypes of BFIS/PKD--mental retardation, episodic ataxia, and
      absences--who were the only individuals to carry a homozygous c.649dupC mutation.
      This family provides strong evidence that homozygous PRRT2 mutations give rise to
      more severe clinical disease of mental retardation, episodic ataxia, and
      absences, and, thus, enlarges the clinical spectrum related to PRRT2 mutations.
      Moreover, it suggests an additive effect of double dose of the genetic mutation
      and underscores the complexity of the phenotypic consequences of mutations in
      this gene.

PMID- 23126440
TI  - Total synthesis of (+/-)-maoecrystal V.
AB  - The total synthesis of racemic maoecrystal V has been accomplished. Key steps
      include an intramolecular Diels-Alder cyclization to rapidly construct the core
      system from simple starting materials and the creation of the A-C ring trans
      fusion through intramolecular delivery of a hydrogen to the hindered beta-face of
      the ring system.

PMID- 23126441
TI  - Influence of cyclic mechanical stretch and tissue constraints on cellular and
      collagen alignment in fibroblast-derived cell sheets.
AB  - Mechanical forces play an important role in shaping the organization of the
      extracellular matrix (ECM) in developing and mature tissues. The resulting
      organization gives the tissue its unique functional properties. Understanding how
      mechanical forces influence the alignment of the ECM is important in tissue
      engineering, where recapitulating the alignment of the native tissue is essential
      for appropriate mechanical anisotropy. In this work, a novel method was developed
      to create and stretch tubular cell sheets by seeding neonatal dermal fibroblasts
      onto a rotating silicone tube. We show the fibroblasts proliferated to create a
      confluent monolayer around the tube and a collagenous, isotropic tubular tissue
      over 4 weeks of static culture. These silicone tubes with overlying tubular
      tissue constructs were mounted into a cyclic distension bioreactor and subjected
      to cyclic circumferential stretch at 5% strain, 0.5 Hz for 3 weeks. We found that
      the tissue subjected to cyclic stretch compacted axially over the silicone tube
      in comparison to static controls, leading to a circumferentially aligned tissue
      with higher membrane stiffness and maximum tension. In a subsequent study, the
      tissue constructs were constrained against axial compaction during cyclic
      stretching. The resulting alignment of fibroblasts and collagen was perpendicular
      (axial) to the stretch direction (circumferential). When the cells were
      devitalized with sodium azide before stretching, similarly constrained tissue did
      not develop strong axial alignment. This work suggests that both mechanical
      stretching and mechanical constraints are important in determining tissue
      organization, and that this organization is dependent on an intact cytoskeleton.

PMID- 23126442
TI  - NMR spectroscopic characterization and DFT calculations of zirconium(IV)-3,3'-Br2
      BINOLate and related complexes used in an enantioselective Friedel-Crafts
      alkylation of indoles with alpha,beta-unsaturated ketones.
AB  - Experimental and theoretical studies on the structure of several complexes based
      on (R)-3,3'-Br(2)-BINOL ligand and group (IV) metals used as catalysts in an
      enantioselective Friedel-Crafts alkylation of indoles with alpha,beta-unsaturated
      ketones have been carried out. NMR spectroscopic studies of these catalysts have
      been performed, which suggested that at room temperature the catalysts would form
      a monomeric structure in the case of Ti(IV) and a dimeric structure in the cases
      of Zr(IV) and Hf(IV). Density functional theory (DFT) calculations clearly
      corroborate the conclusions of these experimental spectroscopic studies. The
      dimeric structure with a doubly bridged motif [Zr(IV)(2)(MU-(R)-3,3'-Br(2)
      BINOL)(2)] where each binaphthol ligand acts as bridge between the metal centers
      (Novak's model) is more stable than the dimeric structure with a doubly bridged
      motif [Zr(IV)(2)(MU-O(t)Bu)(2)] where the tert-butoxide groups act as bridging
      ligands (Kobayashi's model). The scope of the Friedel-Crafts alkylation with
      regard to the indole structure has been studied. Finally a plausible mechanism
      for the Friedel-Crafts reaction and a stereomodel for the mode of action of the
      catalyst that explain the observed stereochemistry of the reaction products have
      been proposed.

PMID- 23126444
TI  - Useful and convenient procedure for intermittent vascular occlusion in
      laparoscopic hepatectomy.
AB  - INTRODUCTION: While the amount of blood loss during laparoscopic hepatectomy
      tends to be smaller than that during open hepatectomy, intermittent vascular
      occlusion to control hepatic inflow can diminish blood loss during laparoscopic
      hepatectomy. Described herein is a useful and convenient method for intermittent
      vascular occlusion, which was standardized for laparoscopic hepatectomy. METHODS:
      A tourniquet system consisting of cloth tape and a 20-cm catheter was used for
      intermittent vascular occlusion. This was placed through a hole in the abdominal
      wall from which a 5-mm trocar had been extracted. By operating this tourniquet
      system outside the patient's body, we were easily able to repeat intermittent
      vascular occlusion. Twenty-three patients underwent laparoscopic hepatectomy
      using this system. RESULTS: The mean time of operation and vascular occlusion
      were 311.6 and 83.6 min, respectively. The mean blood loss was 215.0 mL. There
      were no intraoperative blood transfusions or critical postoperative
      complications. The average length of postoperative hospital stay was 6.5 days.
      The mean time to place this system was 354 s, and there were no complications
      caused by this system. CONCLUSION: During totally laparoscopic hepatectomy,
      surgeons can perform intermittent vascular occlusion safely by using this method.

PMID- 23126443
TI  - Enhanced AMPA receptor activity increases operant alcohol self-administration and
      cue-induced reinstatement.
AB  - Long-term alcohol exposure produces neuroadaptations that contribute to the
      progression of alcohol abuse disorders. Chronic alcohol consumption results in
      strengthened excitatory neurotransmission and increased alpha-amino-3-hydroxyl-5
      methyl-4-isoxazole-propionate receptors (AMPA) receptor signaling in animal
      models. However, the mechanistic role of enhanced AMPA receptor activity in
      alcohol-reinforcement and alcohol-seeking behavior remains unclear. This study
      examined the role of enhanced AMPA receptor function using the selective positive
      allosteric modulator, aniracetam, in modulating operant alcohol self
      administration and cue-induced reinstatement. Male alcohol-preferring (P-) rats,
      trained to self-administer alcohol (15%, v/v) versus water were pre-treated with
      aniracetam to assess effects on maintenance of alcohol self-administration. To
      determine reinforcer specificity, P-rats were trained to self-administer sucrose
      (0.8%, w/v) versus water, and effects of aniracetam were tested. The role of
      aniracetam in modulating relapse of alcohol-seeking was assessed using a response
      contingent cue-induced reinstatement procedure in P-rats trained to self
      administer 15% alcohol. Aniracetam pre-treatment significantly increased alcohol
      reinforced responses relative to vehicle treatment. This increase was not
      attributed to aniracetam-induced hyperactivity as aniracetam pre-treatment did
      not alter locomotor activity. AMPA receptor involvement was confirmed because 6,7
      dinitroquinoxaline-2,3-dione (AMPA receptor antagonist) blocked the aniracetam
      induced increase in alcohol self-administration. Aniracetam did not alter sucrose
      reinforced responses in sucrose-trained P-rats, suggesting that enhanced AMPA
      receptor activity is selective in modulating the reinforcing function of alcohol.
      Finally, aniracetam pre-treatment potentiated cue-induced reinstatement of
      alcohol-seeking behavior versus vehicle-treated P-rats. These data suggest that
      enhanced glutamate activity at AMPA receptors may be key in facilitating alcohol
      consumption and seeking behavior, which could ultimately contribute to the
      development of alcohol abuse disorders.

PMID- 23126445
TI  - Expression of lymphangiogenic vascular endothelial growth factor family members
      in bovine corpus luteum.
AB  - The aim of this study was to evaluate mRNA expression, protein concentration and
      localization of the assumedly important lymphangiogenic factors VEGFC and VEGFD
      and the receptor FLT4 in bovine corpora lutea (CL) during different physiological
      stages. In experiment 1, CL were collected in a slaughterhouse and stages (days 1
      2, 3-4, 5-7, 8-12, 13-16, >18) of oestrous cycle and month <3, 3-5, 6-7 and >8 of
      pregnancy. In experiment 2, prostaglandin F2alpha (PGF)-induced luteolysis was
      performed in 30 cows, which were injected with PGF analogue on day 8-12 (mid
      luteal phase), and CL were collected before and 0.5, 2, 4, 12, 24, 48 and 64 h
      after PGF injection. The mRNA expression was characterized by RT-qPCR. All three
      factors were clearly expressed and showed significant changes during different
      groups and periods examined in both experiments. Protein concentrations of VEGFD
      and FLT4 measured by ELISA were not detectable in early cyclic CL but increased
      to higher plateau levels during pregnancy. After PGF-induced luteolysis FLT4
      protein showed an increase within 2-24 h after the injection. FLT4 localization
      by immunohistochemistry in the cytoplasm of luteal cells was relatively weak in
      early CL. It increased in late CL and especially in CL during pregnancy. During
      pregnancy, a positive FLT4 staining in both the nucleus and cytoplasm of
      lymphatic endothelial cells in peripheral tissue was observed. In conclusion, our
      results lead to the assumption that lymphangiogenic factors are produced and
      regulated in CL and may be involved in mechanisms regulating CL function,
      especially during pregnancy.

PMID- 23126446
TI  - Rhodium-catalyzed carbon-silicon bond activation for synthesis of benzosilole
      derivatives.
AB  - A rhodium-catalyzed coupling reaction of 2-trimethylsilylphenylboronic acid with
      internal alkynes is developed for the synthesis of 2,3-disubstituted benzosilole
      derivatives. A range of functional groups, encompassing ketones, esters, amines,
      aryl bromides, and heteroarenes, are compatible, which provides rapid access to
      diverse benzosiloles. Sequential 2-fold coupling enables modular synthesis of
      asymmetrically substituted 1,5-dihydro-1,5-disila-s-indacene, a pi-extended
      molecule of interest in organic electronics. In terms of the mechanism, the
      reaction involves cleavage of a C(alkyl)-Si bond in a trialkylsilyl group, which
      normally requires extremely harsh conditions for activation. Mechanistic studies,
      including effects of substituents, reveal that C-Si bond cleavage does not
      proceed through a hypercoordinated silicon species, but rather through a rhodium
      mediated activation process. The potential use of the reaction in catalytic
      asymmetric synthesis of Si-chiral benzosiloles is also demonstrated.

PMID- 23126447
TI  - Depression is associated with longer emergency department length of stay in acute
      coronary syndrome patients.
AB  - BACKGROUND: Patient demographic characteristics have been associated with longer
      emergency department (ED) treatment times, but the influence of psychosocial
      characteristics has not been assessed. We evaluated whether depression was
      associated with greater ED length of stay (LOS) in non-ST elevation myocardial
      infarction (NSTEMI) and unstable angina (UA) patients presenting to a large
      metropolitan academic medical center. METHODS: We calculated ED LOS for NSTEMI or
      UA patients enrolled an observational cohort study by taking the difference
      between ED triage time in the medical record and time of transfer to an inpatient
      bed from standardized transfer documentation forms. Depression status was defined
      as current, past, or never by clinical interview and also by self-report on the
      Beck Depression Inventory. RESULTS: Participants were 120 NSTEMI/UA patients
      [mean age= 62, 36% women, 56% Hispanic, 26% Black/African American, 40% NSTEMI,
      mean global registry of acute cardiac events (GRACE) score= 93.9]. Mean ED LOS
      was 11.6 hours, SD= 8.3. A multiple linear regression model that included the
      above demographic and clinical variables, and time of presentation to ED,
      explained 11% of the variance in ED LOS, F (11, 108)= 2.35, p= .01, R2 adj.= .11.
      Currently depressed patients spent 5.4 more hours (95% CI= .40, 10.4 hours) in
      the ED on average than patients who had never been depressed. CONCLUSIONS:
      Currently depressed NSTEMI/UA patients are in the ED for an average of 5 hours
      longer than those who have never been depressed. Further research is needed to
      identify the reasons for this difference.

PMID- 23126448
TI  - Development of a multiplex PCR for the identification of pathogenic Edwardsiella
      tarda and application to edwardsiellosis diagnostics.

PMID- 23126449
TI  - Migraine treated using a prophylactic combination of candesartan and
      hydrochlorothiazide (ECARD Combination Tablets LD).
AB  - We describe the use of the antihypertensive, candesartan, with
      hydrochlorothiazide (ECARD Combination Tablets LD) as a preventive therapy that
      decreased the frequency of migraine accompanied by premonitory leg edema. Two
      women (aged 26 and 50 years) presented to hospital with an increasing frequency
      of migraine without aura accompanied by leg edema. We prescribed ECARD half
      tablet (candesartan, 2 mg and hydrochlorothiazide, 3.125 mg), and the migraines
      and leg edema disappeared. The use of ECARD to treat a series of migraines by
      controlling premonitory leg edema has not been reported. ECARD, combined with a
      low-dose diuretic, may have been helpful in these patients with the premonitory
      migraine symptom of leg edema.

PMID- 23126450
TI  - Quasi-real time quantification of uric acid in urine using boron doped diamond
      microelectrode with in situ cleaning.
AB  - We report herein an innovative electrochemical (EC) technique based on boron
      doped diamond (BDD) microelectrodes which enable the fast determination of uric
      acid (UA) concentrations in urine. On the basis of fast cyclic voltammetry (CV),
      the technique was assessed in human urine samples and compared successfully using
      routine spectrophotometric diagnosis. The approach relies on the use of BDD's
      superior properties such as low background current, low adsorption of species,
      long-term stability, and antifouling capabilities using electrochemical
      reactivation. Moreover, the article also describes an in situ activation
      technique, where the electrodes were reactivated within human urine, thereby
      opening the way toward automatic quantification of UA with in situ cleaning. The
      time taken to quantify UA concentration and cleaning remains below 0.5 s. Two
      analytic models were derived, based on different concentrations of ascorbic acid
      (AA) and uric acid, consisting of 2 s order calibration curves. Solving the
      second order equation enables the direct estimation of UA concentration, and
      values demonstrated good accuracy when compared with spectrophotometric
      measurements.

PMID- 23126451
TI  - Concentrations of free amino acids and sugars in nine potato varieties: effects
      of storage and relationship with acrylamide formation.
AB  - Acrylamide forms during cooking and processing predominately from the reaction of
      free asparagine and reducing sugars in the Maillard reaction. The identification
      of low free asparagine and reducing sugar varieties of crops is therefore an
      important target. In this study, nine varieties of potato (French fry varieties
      Maris Piper (from two suppliers), Pentland Dell, King Edward, Daisy, and Markies;
      and chipping varieties Lady Claire, Lady Rosetta, Saturna, and Hermes) grown in
      the United Kingdom in 2009 were analyzed at monthly intervals through storage
      from November 2009 to July 2010. Acrylamide formation was measured in heated
      flour and chips fried in oil. Analysis of variance revealed significant
      interactions between varieties nested within type (French fry and chipping) and
      storage time for most free amino acids, glucose, fructose, and acrylamide
      formation. Acrylamide formed in chips correlated significantly with acrylamide
      formed in flour and with chip color. There were significant correlations between
      glucose or total reducing sugar concentration and acrylamide formation in both
      variety types, but with fructose the correlation was much stronger for chipping
      than for French fry varieties. Conversely, there were significant correlations
      with acrylamide formation for both total free amino acid and free asparagine
      concentration in the French fry but not chipping varieties. The study showed the
      potential of variety selection for preventing unacceptable levels of acrylamide
      formation in potato products and the variety-dependent effect of long-term
      storage on acrylamide risk. It also highlighted the complex relationship between
      precursor concentration and acrylamide risk in potatoes.

PMID- 23126452
TI  - Robotic versus laparoscopic partial nephrectomy for tumor in a solitary kidney: a
      single institution comparative analysis.
AB  - OBJECTIVES: To compare the outcomes of robot-assisted laparoscopic partial
      nephrectomy and laparoscopic partial nephrectomy for renal tumor in patients with
      a solitary kidney. METHODS: We retrospectively reviewed data of patients with
      solitary kidney who underwent laparoscopic (n = 52) and robot-assisted (n = 15)
      partial nephrectomy for renal tumor at Cleveland Clinic, Cleveland, Ohio, USA,
      between June 2000 and April 2012. Patient demographic data, perioperative
      parameters and follow-up data were compared. RESULTS: The two groups were similar
      in terms of patients and tumor characteristics, including preoperative renal
      function and etiology of solitary kidney. The median operative time (225 vs 171
      min, P = 0.02), warm ischemia time (19 vs 15 min, P = 0.04) and hospital stay (4
      vs 3 days, P = 0.03) were significantly shorter in the robotic group. No
      significant differences were found in terms of estimated blood loss, transfusion,
      complications, pathological results and margin status. The median percentage
      change of renal function was not significantly different between two groups. Long
      term hemodialysis was required for three patients in the laparoscopic group (6%)
      and none of the patients in the robotic group. Median follow up was 15.6 and 5.9
      months in the laparoscopic and robotic group, respectively. CONCLUSIONS: Robot
      assisted partial nephrectomy represents a safe and effective minimally-invasive
      treatment option for renal masses in patients with a solitary kidney. Early
      comparative outcomes suggest that it offers a significant benefit over the
      laparoscopic approach in terms of operative time, warm ischemia time and hospital
      stay. Further studies with a longer follow up are required to confirm the
      likelihood of better long-term functional and oncological outcomes.

PMID- 23126453
TI  - Risk of large-scale evacuation based on the effectiveness of rescue strategies
      under different crowd densities.
AB  - Crowd density is a key factor that influences the moving characteristics of a
      large group of people during a large-scale evacuation. In this article, the macro
      features of crowd flow and subsequent rescue strategies were considered, and a
      series of characteristic crowd densities that affect large-scale people movement,
      as well as the maximum bearing density when the crowd is extremely congested,
      were analyzed. On the basis of characteristic crowd densities, the queuing theory
      was applied to simulate crowd movement. Accordingly, the moving characteristics
      of the crowd and the effects of typical crowd density-which is viewed as the
      representation of the crowd's arrival intensity in front of the evacuation
      passageways-on rescue strategies was studied. Furthermore, a "risk axle of crowd
      density" is proposed to determine the efficiency of rescue strategies in a large
      scale evacuation, i.e., whether the rescue strategies are able to effectively
      maintain or improve evacuation efficiency. Finally, through some rational
      hypotheses for the value of evacuation risk, a three-dimensional distribution of
      the evacuation risk is established to illustrate the risk axle of crowd density.
      This work aims to make some macro, but original, analysis on the risk of large
      scale crowd evacuation from the perspective of the efficiency of rescue
      strategies. 

PMID- 23126454
TI  - The role of planktonic Flavobacteria in processing algal organic matter in
      coastal East Antarctica revealed using metagenomics and metaproteomics.
AB  - Heterotrophic marine bacteria play key roles in remineralizing organic matter
      generated from primary production. However, far more is known about which groups
      are dominant than about the cellular processes they perform in order to become
      dominant. In the Southern Ocean, eukaryotic phytoplankton are the dominant
      primary producers. In this study we used metagenomics and metaproteomics to
      determine how the dominant bacterial and archaeal plankton processed bloom
      material. We examined the microbial community composition in 14 metagenomes and
      found that the relative abundance of Flavobacteria (dominated by Polaribacter)
      was positively correlated with chlorophyll a fluorescence, and the relative
      abundance of SAR11 was inversely correlated with both fluorescence and
      Flavobacteria abundance. By performing metaproteomics on the sample with the
      highest relative abundance of Flavobacteria (Newcomb Bay, East Antarctica) we
      defined how Flavobacteria attach to and degrade diverse complex organic material,
      how they make labile compounds available to Alphaproteobacteria (especially
      SAR11) and Gammaproteobacteria, and how these heterotrophic Proteobacteria target
      and utilize these nutrients. The presence of methylotrophic proteins for archaea
      and bacteria also indicated the importance of metabolic specialists. Overall, the
      study provides functional data for the microbial mechanisms of nutrient cycling
      at the surface of the coastal Southern Ocean.

PMID- 23126455
TI  - Adolescents at risk of psychosis have higher level of hopelessness than
      adolescents not at risk of psychosis.
AB  - BACKGROUND: Hopelessness has been a widely studied phenomenon in psychotic
      disorders. However, previous evidence of hopelessness in at-risk state of
      psychosis is lacking. The primary aim of the present study was to investigate
      associations between at-risk state of psychosis and the level of hopelessness,
      the secondary aim being to investigate, at item-level, hopelessness differences
      in hopelessness profile of adolescents at risk of psychosis. METHODS:
      Hopelessness was assessed with the Beck Hopelessness Scale (BHS) and risk of
      psychosis with the PROD screen by an early detection team at the Helsinki
      University Central Hospital in a sample of 200 help-seeking adolescents between
      11 and 22 years of age. Of them, 66 were classified as belonging to the at-risk
      of psychosis group and 134 to the not-at-risk of psychosis group. RESULTS: The at
      risk group scored higher in total sum scores of hopelessness than the not-at-risk
      group (9.15 vs. 6.63, P = 0.002). In an additional analysis of the BHS, the sub
      item "I have great faith in the future" (P < 0.001) differed by risk status of
      psychosis after correction for multiple analysis. In a logistic regression
      analysis, BHS subfactor III (sum scores of items "I can't imagine what my life
      would be like in 10 years" and "I don't expect to get what I really want")
      explained (P = 0.047) the at-risk status of psychosis after age, gender and other
      BHS subfactors had been adjusted for. CONCLUSIONS: Adolescents at risk of
      psychosis have higher hopelessness than other help-seekers. In light of a
      heightened possibility of suicidal behaviour, psychiatric care should pay
      attention to these findings.

PMID- 23126456
TI  - Malpractice awareness among surgeons at a teaching hospital in Pakistan.
AB  - BACKGROUND: The duty of a doctor to take care presumes the person who offers
      medical advice and treatment to unequivocally possess the skills and knowledge to
      do so. However, a sense of responsibility cannot be guaranteed in the absence of
      accountability, which in turn requires a comprehensive medical law system to be
      in place. Such a system is almost non-existent in Pakistan. Keeping the above in
      mind, we designed this study to assess the knowledge, attitudes and practices of
      surgeons regarding malpractice at a tertiary care center in Pakistan. METHODS:
      This was an observational, cross-sectional, questionnaire-based study conducted
      during a three month period from 31st March, 2012 to 30th June, 2012 at Civil
      Hospital, Karachi. Surgeons who were available during the period of our study and
      had been working in the hospital for at least 6 months were included. Self
      administered questionnaires were distributed after seeking informed, written
      consent. The specialties included were general surgery, cardiothoracic surgery,
      neurosurgery, ophthalmology, otolaryngology, plastic surgery, pediatric surgery,
      orthopedic surgery, oral and maxillofacial surgery and gynecology and obstetrics.
      The study questionnaire comprised of four sections. The first section was
      concerned with the demographics of the surgeons. The second section analyzed the
      knowledge of the respondents regarding professional negligence and malpractice.
      The third section assessed the attitudes surgeons with regard to malpractice. The
      last section dealt with the general and specific practices and experiences of
      surgeons regarding malpractice. RESULTS: Of the 319 surgeons interviewed, 68.7%
      were oblivious of the complete definition of malpractice. Leaving foreign objects
      inside the patient (79.6%) was the most commonly agreed upon form of malpractice,
      whereas failure to break news in entirety (43.9%) was most frequently disagreed.
      In the event of a medical error, majority (67.7%) were ready to disclose their
      error to the patient. The most common perceived reason for not disclosing the
      error was threat of a claim or assault (90.9%). Majority (68.3%) believed that
      malpractice had a negative effect on reputation. Only 13(4.1%) had received at
      least one legal claim for damages. Only about three-fourths (75.5%) had the habit
      of frequently obtaining informed consent from the patients. 83(26.0%) expressed
      reluctance in accepting a case that was deemed to be difficult. Financial gains
      and liabilities were responsible for biased approach in 8.5% and 12.2% of the
      respondents respectively. CONCLUSION: There is a dire need of programs aimed at
      increasing awareness among practicing surgeons in our setup. Proactive measures
      are required for the formulation of an efficient system of litigation. Physician
      accountability will not only arouse a greater sense of responsibility in them,
      but will also augment the confidence placed by patients on the healthcare system.

PMID- 23126457
TI  - Debt, shame, and survival: becoming and living as widows in rural Kerala, India.
AB  - BACKGROUND: The health and well-being of widows in India is an important but
      neglected issue of public health and women's rights. We investigate the lives of
      Indian women as they become widows, focussing on the causes of their husband's
      mortality and the ensuing consequences of these causes on their own lives and
      identify the opportunities and challenges that widows face in living healthy and
      fulfilling lives. METHODS: Data were collected in a Gram Panchayat (lowest level
      territorial decentralised unit) in the south Indian state of Kerala. Interviews
      were undertaken with key informants in order to gain an understanding of local
      constructions of 'widowhood' and the welfare and social opportunities for widows.
      Then we conducted semi-structured interviews with widows in the community on
      issues related to health and vulnerability, enabling us to hear perspectives from
      widows. Data were analysed for thematic content and emerging patterns. We
      synthesized our findings with theoretical understandings of vulnerability and
      Amartya Sen's entitlements theory to develop a conceptual framework. RESULTS: Two
      salient findings of the study are: first, becoming a widow can be viewed as a
      type of 'shock' that operates similarly to other 'economic shocks' or 'health
      shocks' in poor countries except that the burden falls disproportionately on
      women. Second, widowhood is not a static phenomenon, but rather can be viewed as
      a multi-phased process with different public health implications at each stage.
      CONCLUSION: More research on widows in India and other countries will help to
      both elucidate the challenges faced by widows and encourage potential solutions.
      The framework developed in this paper could be used to guide future research on
      widows.

PMID- 23126458
TI  - Food and Drug Administration (FDA) drug approval end points for chronic cutaneous
      ulcer studies.
AB  - The rising costs of caring for chronic cutaneous ulcers (CCUs) and recent
      appreciation of the mortality of CCUs have led to consideration of the reasons
      for the failure to have new drug therapies. No new chemical entities to heal CCUs
      have been approved by the Food and Drug Administration (FDA) in over a decade, in
      part due to an inability to reach the FDA accepted end point of "complete wound
      closure." The frequent failure to reach the complete closure end point brings
      forward the question of the relevance of other healing end points such as
      improved quality of life, or partial healing. Because CCUs carry a prognosis and
      mortality rate worse than many cancers, it is reasonable to compare the FDA trial
      end points for cancer drug approval with those for CCUs. And the difference is
      quite striking. While there is only one end point for CCUs, there are five
      surrogate and three direct end points for cancers. In contrast to cancer,
      surrogate end points and partial healing are not acceptable for therapies aimed
      at CCUs. For example, making tumors smaller is an acceptable end point, but
      making CCUs smaller is not and improvement in the signs and symptoms of cancer is
      an acceptable end point for cancers but not CCUs. As CCUs carry a prognosis and
      mortality rate worse than many cancers, we believe a reconsideration of end
      points for CCUs is highly warranted.

PMID- 23126459
TI  - Histopathologic staining of low temperature cutaneous burns: comparing biomarkers
      of epithelial and vascular injury reveals utility of HMGB1 and hematoxylin
      phloxine saffron.
AB  - Histopathology remains the gold standard for evaluation of burn depth,
      progression, and healing, but burn literature offers little guidance on the best
      stains for analysis of these complex and evolving injuries. A battery of
      histochemical and immunohistochemical stains was compared on adjacent sections to
      determine the best stains for histopathologic study and imaging of burns. Using a
      validated porcine model of vertical burn progression, full-thickness cutaneous
      biopsies were stained using hematoxylin and eosin, Hematoxylin phloxine saffron
      (HPS), Masson Trichrome, Elastin Von Gieson, Movatt's Pentachrome, vimentin,
      CD31, KI-67, caspase 3a, and high mobility group box 1. Depth of collagen
      degeneration, cellular necrosis, apoptosis, and vascular occlusion; and
      reparative processes of cellular hyperplasia, reepithelialization, and new
      collagen deposition were measured by ocular microscopy. High mobility group box 1
      was superior for necrosis between 1 and 24 hours postburn. Vimentin
      underestimated necrosis until 48 hours postburn. For overall assessment,
      hematoxylin and eosin and HPS were comparable, except for analysis of thermally
      injured collagen, vessel occlusion, erythrocyte extravasation, and polariscopic
      study of collagen deposition, where HPS was superior. HPS stain offers specific
      advantages in histopathologic burn analysis. Inexpensive and rapid to produce,
      HPS allows users to analyze eosinophilic components more precisely than standard
      hematoxylin and eosin.

PMID- 23126460
TI  - Mesial temporal lobe epilepsy as a neuropsychiatric syndrome of systemic lupus
      erythematosus.
AB  - In this study, we aimed to investigate the types of seizures and epilepsy
      associated with systemic lupus erythematosus (SLE). We searched the medical
      records at a tertiary referral center to identify a cohort of epilepsy patients
      with SLE who were treated between January 2000 and August 2011. We analyzed the
      clinical and immunologic profiles of these patients, their seizure and epilepsy
      classifications, electroencephalography (EEG) and magnetic resonance imaging
      (MRI) assessments, and the treatment administered for epilepsy and SLE. As the
      result, 17 patients with SLE and epilepsy were identified. Seven patients had
      mesial temporal lobe epilepsy (MTLE), eight had epilepsy secondary to stroke, and
      two had generalized epilepsy. Of the seven patients with MTLE, anteriotemporal
      spikes were noted in all patients with EEG, and MRI findings suggesting
      hippocampal sclerosis were noted in four patients. Clobazam and levetiracetam
      were effective in treating three patients, and one patient underwent
      amygdalohippocampectomy. In conclusion, MTLE may be a characteristic
      manifestation of neuropsychiatric syndrome of systemic lupus erythematosus.

PMID- 23126461
TI  - Risk factors for postconcussion symptom reporting after traumatic brain injury in
      U.S. military service members.
AB  - The purpose of this study was to identify factors that are predictive of, or
      associated with, postconcussion symptom reporting after traumatic brain injury
      (TBI) in the U.S. military. Participants were 125 U.S. military service members
      (age: M=29.6 years, standard deviation [SD]=8.9, range=18-56 years) who sustained
      a TBI, divided into two groups based on symptom criteria for postconcussional
      disorder (PCD): PCD-Present (n=65) and PCD-Absent (n=60). Participants completed
      a neuropsychological evaluation at Walter Reed Army Medical Center (M=9.4 months
      after injury, SD=9.9; range: 1.1 to 44.8). Factors examined included demographic
      characteristics, injury-related variables, psychological testing, and effort
      testing. There were no significant group differences for age, sex, education,
      race, estimated premorbid intelligence, number of deployments, combat versus non
      combat related injury, or mechanism of injury (p>0.098 for all). There were
      significant main effects for severity of body injury, duration of loss of
      consciousness, duration of post-traumatic amnesia, intracranial abnormality, time
      tested post-injury, possible symptom exaggeration, poor effort, depression, and
      traumatic stress (p<0.044 for all). PCD symptom reporting was most strongly
      associated with possible symptom exaggeration, poor effort, depression, and
      traumatic stress. PCD rarely occurred in the absence of depression, traumatic
      stress, possible symptom exaggeration, or poor effort (n=7, 5.6%). Many factors
      unrelated to brain injury were influential in self-reported postconcussion
      symptoms in this sample. Clinicians cannot assume uncritically that endorsement
      of items on a postconcussion symptom checklist is indicative of residual effects
      from a brain injury.

PMID- 23126463
TI  - Identification of two novel HLA alleles: HLA-DRB1*12:03:03 and HLA-DRB1*13:143.
AB  - The novel alleles DRB1*12:03:03 and DRB1*13:143 differ from DRB1*12:03:02 and
      DRB1*13:02:01 by one nucleotide in exon 2, respectively.

PMID- 23126464
TI  - Nonlinear optical thin film device from a chiral octopolar phenylacetylene liquid
      crystal.
AB  - A set of chiral discotic phenylacetylenes have been synthesized by 3-fold
      Sonogashira coupling between different ethynylbenzenes and triiodobenzenes. The
      resultant bulk materials are fully characterized by polarized optical microscopy
      (POM), differential scanning calorimetry (DSC), and X-ray diffraction. The
      octopolar nature of the target compounds is studied by UV-vis absorption
      spectroscopy and hyper-Raleigh scattering in solution. Optimization of the donor
      acceptor substitution yields both high hyperpolarizability values and appreciable
      mesomorphic properties. A simple thin film device for second harmonic generation
      has been prepared from the nitro-substituted liquid crystalline derivative.

PMID- 23126465
TI  - Xenofree enzymatic products for the isolation of human adipose-derived
      stromal/stem cells.
AB  - Human adipose-derived stromal/stem cells (ASCs) are an abundant, readily
      available population of adult stem cells that reside in adipose tissue and that
      have a great potential utility for tissue engineering and regenerative medicine
      therapeutic applications. Several preclinical studies have shown that ASCs have
      therapeutic applicability, but a standardized isolation and expansion methodology
      for clinical cell therapy has yet to be established. ASC are typically isolated
      and expanded using reagents with xenogenic components and this may pose certain
      risks and safety issues, such as exposure to infectious agents and immune
      reactions, creating further obstacles to the translation of ASC-based therapies
      to clinical scenarios. The objective of this study was to determine the
      suitability and efficacy of various alternative enzymatic products, CLS1
      (Worthington), CLSAFA (Worthington), NB4 (SERVA), and Liberase (Roche), for the
      digestion of adipose tissue and subsequent isolation of ASCs, assessing cell
      functionality concerning their proliferation and differentiation ability. Results
      show that there are no statistically significant differences on yield and
      proliferation of cells isolated after enzymatic digestion with any of the studied
      products. The differentiation potential of the cells was not affected, and cell
      surface marker expression was similar among all products. We concluded that
      clinical grade products can replace current research-grade products effectively
      in our cell isolation protocols without any negative effect in the yield or
      function of human ASCs.

PMID- 23126466
TI  - Cell-cycle analysis and micronuclei frequency reveals G0/G1 blockers as weak
      micronuclei inducers.
AB  - Micronuclei (MN) formation is generally attributed to error in DNA synthesis or
      mitosis, which are represented by the S or G(2)/M phase respectively, in the cell
      cycle histogram. Interestingly, many of the known anticancer drugs target these
      cell-cycle phases to elicit cytotoxicity. Here, we attempted to identify whether
      any correlation exists between the cell-cycle effect and MN induction potential
      using various treatments. In addition, we tracked down MN in cycling cells to
      assess its final fate. We treated SiHa cells with various known drugs and
      correlated their effects on cell-cycle and MN frequency. MN-tracking studies were
      performed in peripheral mononuclear and siHa cells upon staining with Giemsa and
      ethidium bromide respectively. We observed MN induction by all the tested drugs
      irrespective of their basic effect on cell cycle. However, MN induction was more
      with drugs which interfere with the S or G(2)/M than the G(0)/G(1) phase. Our
      results indicate G(0)/G(1) blockers to be comparatively safer drugs.
      Additionally, our results show that expulsion out of cells may be one of the main
      fates of drug-induced MN.

PMID- 23126467
TI  - Morphological tuning of polymeric nanoparticles via microfluidic platform for
      fuel cell applications.
AB  - At nanoscale length scales, the properties of particles change rapidly with the
      slightest change in dimension. The use of a microfluidic platform enables precise
      control of sub-100 nm organic nanoparticles (NPs) based on polybenzimidazole.
      Using hydrodynamic flow focusing, we can control the size and shape of the NPs,
      which in turn controls a number of particle material properties. The anhydrous
      proton-conducting nature of the prepared NPs allowed us to make a high
      performance ion exchange membrane for fuel cell applications, and microfluidic
      tuning of the NPs allowed us subsequently to tune the fuel cell performance.

PMID- 23126468
TI  - Health problems and male firearm suicide.
AB  - Drawing on constructs of masculinity as it relates to both gun ownership and
      men's health, we use a rich data set, the New Jersey Violent Death Reporting
      System as well as hospital discharge data, to analyze 3,413 completed male
      suicides between the years of 2003 and 2009. We test the hypotheses that the use
      of firearms is more common when physical health problems are cited as suicide
      circumstances, and that suicide decedents who use firearms have poorer physical
      health than those who used other methods. Results show that firearms are
      disproportionately used in male suicides when physical health is listed as a
      circumstance. Additionally, among suicide decedents with a hospitalization during
      the 3 years prior to death, those who used firearms were in poorer health than
      those who used other methods. These findings have implications for prevention
      efforts, because restricting access to lethal means is an important aspect of
      suicide prevention.

PMID- 23126470
TI  - Extension of a classic low frequency dielectric dispersion theory of colloidal
      suspensions to include different counterion and co-ion valences, a broad
      frequency range, and the stagnant layer conductivity.
AB  - A unified extension of the classic Shilov-Dukhin theory of the low frequency
      dielectric dispersion of colloidal dispersions is presented. Purely analytical
      expressions for the AC dielectric and electrokinetic response over a broad
      frequency range including different counterion and co-ion valences and the
      presence of the stagnant layer conductivity are deduced. The obtained results are
      generally in good to very good agreement with available numerical data, showing
      that they should be useful for the interpretation of a broad range of
      experimental results without having to rely on numerical calculations.

PMID- 23126469
TI  - MCMC-ODPR: primer design optimization using Markov Chain Monte Carlo sampling.
AB  - BACKGROUND: Next generation sequencing technologies often require numerous primer
      designs that require good target coverage that can be financially costly. We
      aimed to develop a system that would implement primer reuse to design degenerate
      primers that could be designed around SNPs, thus find the fewest necessary
      primers and the lowest cost whilst maintaining an acceptable coverage and provide
      a cost effective solution. We have implemented Metropolis-Hastings Markov Chain
      Monte Carlo for optimizing primer reuse. We call it the Markov Chain Monte Carlo
      Optimized Degenerate Primer Reuse (MCMC-ODPR) algorithm. RESULTS: After repeating
      the program 1020 times to assess the variance, an average of 17.14% fewer primers
      were found to be necessary using MCMC-ODPR for an equivalent coverage without
      implementing primer reuse. The algorithm was able to reuse primers up to five
      times. We compared MCMC-ODPR with single sequence primer design programs Primer3
      and Primer-BLAST and achieved a lower primer cost per amplicon base covered of
      0.21 and 0.19 and 0.18 primer nucleotides on three separate gene sequences,
      respectively. With multiple sequences, MCMC-ODPR achieved a lower cost per base
      covered of 0.19 than programs BatchPrimer3 and PAMPS, which achieved 0.25 and
      0.64 primer nucleotides, respectively. CONCLUSIONS: MCMC-ODPR is a useful tool
      for designing primers at various melting temperatures at good target coverage. By
      combining degeneracy with optimal primer reuse the user may increase coverage of
      sequences amplified by the designed primers at significantly lower costs. Our
      analyses showed that overall MCMC-ODPR outperformed the other primer-design
      programs in our study in terms of cost per covered base.

PMID- 23126471
TI  - Differential effects of baclofen and oxytocin on the increased ethanol
      consumption following chronic psychosocial stress in mice.
AB  - Chronic stress is known to enhance the susceptibility for addiction disorders
      including alcoholism. While these findings have been recapitulated in animal
      models, the majority of these studies have utilized non-social rather than social
      stress paradigms; the latter of which are believed to be more relevant to the
      human situation. Therefore, the major aim of this study was to investigate, if 14
      days of chronic subordinate colony housing (CSC), a pre-clinically validated
      psychosocial stress paradigm relevant for human psychiatric and somatic
      disorders, enhances ethanol (EtOH) consumption in male mice. To assess this, we
      employed the well-established two-bottle free-choice paradigm where mice were
      given access to water and 2, 4, 6 and 8% EtOH solutions (with the concentrations
      increasing each fourth day) following termination of the stress procedure. After
      14 days of CSC, stressed mice consumed significantly more EtOH at all
      concentrations tested and displayed increased EtOH preference at concentrations
      of 6 and 8%. This effect was not due to an altered taste preference in CSC mice
      as assessed by saccharine- and quinine-preference tests, but was accompanied by
      increased anxiety-related behavior. Systemic administration of baclofen (2.5
      mg/kg) or oxytocin (OXT; 10 mg/kg) reduced the EtOH intake in single housed
      control (baclofen, OXT) and CSC (baclofen) mice, whereas intracerebroventricular
      OXT (0.5 MUg/2 MUl) was ineffective in both groups. Taken together, these results
      suggest that (i) chronic psychosocial stress enhances EtOH consumption, and (ii)
      baclofen and OXT differentially affect EtOH intake in mice.

PMID- 23126472
TI  - Microstructure of single chain quaternary ammonium cations intercalated into
      montmorillonite: a molecular dynamics study.
AB  - This study uses molecular dynamics (MD) modeling to examine the interlayer
      microstructures of montmorillonite intercalated with single chain QACs. Three
      types of QACs-tetramethylammonium (TMA), decyltrimethylammonium (DTMA), and
      hexadecyltrimethylammonium (HDTMA)-were selected to synthesize the organoclay
      complex, and the surfactant arrangement was analyzed quantitatively in systems in
      the absence of water. A series of arrangement patterns of interlayer QAC
      surfactant were observed, including lateral monolayers, lateral bilayers,
      pseudotrilayers, and paraffin monolayers, in agreement with previous experimental
      results. The effects of increasing one carbon chain length and amount of loading
      of QAC on the resultant QAC arrangement are summarized, yielding a model that
      provides insight into the prediction of synthesized QAC-clay microstructure and
      engineering behavior in practice.

PMID- 23126473
TI  - Duration of patients' visits to the hospital emergency department.
AB  - BACKGROUND: Length of stay is an important indicator of quality of care in
      Emergency Departments (ED). This study explores the duration of patients' visits
      to the ED for which they are treated and released (T&R). METHODS: Retrospective
      data analysis and multivariate regression analysis were conducted to investigate
      the duration of T&R ED visits. Duration for each visit was computed by taking the
      difference between admission and discharge times. The Healthcare Cost and
      Utilization Project (HCUP) State Emergency Department Databases (SEDD) for 2008
      were used in the analysis. RESULTS: The mean duration of T&R ED visit was 195.7
      minutes. The average duration of ED visits increased from 8 a.m. until noon, then
      decreased until midnight at which we observed an approximately 70-minute spike in
      average duration. We found a substantial difference in mean duration of ED visits
      (over 90 minutes) between Mondays and other weekdays during the transition time
      from the evening of the day before to the early morning hours. Black / African
      American patients had a 21.4-minute longer mean duration of visits compared to
      white patients. The mean duration of visits at teaching hospitals was
      substantially longer than at non-teaching hospitals (243.8 versus 175.6 minutes).
      Hospitals with large bed size were associated with longer duration of visits
      (222.2 minutes) when compared to hospitals with small bed size (172.4 minutes) or
      those with medium bed size (166.5 minutes). The risk-adjusted results show that
      mean duration of visits on Mondays are longer by about 4 and 9 percents when
      compared to mean duration of visits on non-Monday workdays and weekends,
      respectively. CONCLUSIONS: The duration of T&R ED visits varied significantly by
      admission hour, day of the week, patient volume, patient characteristics,
      hospital characteristics and area characteristics.

PMID- 23126474
TI  - Change in infectivity titre of nervous necrosis virus (NNV) in brain tissue of
      sevenband grouper, Epinephalus fasciatus Thunberg, with Poly(I:C) administration.

PMID- 23126475
TI  - Duloxetine and pregabalin for pain management in multiple rheumatic diseases
      associated with fibromyalgia.
AB  - The fibromyalgia syndrome (FMS) is characterized by chronic and widespread
      musculoskeletal pain and soreness accompanied by sleep disorders, chronic fatigue
      and affective disorders. FMS is often associated with other forms of immuno
      rheumatic diseases. Although FMS pathophysiology is still not fully understood, a
      number of neuroendocrine, neurotransmission and neurosensitive disorders might
      generate a mechanism for the elicitation of pain by "central sensitization,"
      which is common to many other painful conditions. The present case describes the
      success of a therapeutic scheme, which associates two different pharmacological
      classes, anticonvulsants and new-generation antidepressants, when FMS complicates
      a rare pathology called Cogan's syndrome. The association of two drugs might
      noticeably affect the molecular mechanisms of difficult pain, thus solving
      painful conditions of multifactorial origin. 

PMID- 23126476
TI  - Quantitative analysis of deamidation and isomerization in beta2-microglobulin by
      18O labeling.
AB  - Deamidation of asparagine residues in proteins via the formation of a 5-membered
      succinimide ring intermediate is a nonenzymatic intramolecular reaction and, in
      general, occurs most rapidly at an Asn-Gly sequence. A protein containing this
      sequence would, therefore, be susceptible to modification, and the result would
      produce a structural alteration in the molecule. An Asn would be replaced with an
      Asp, resulting in an increase in the overall negative charge on the molecule but
      also an isomerization to isoAsp. Despite the fact that such a structural
      replacement could affect the functional properties of a protein, estimating the
      susceptibility of the Asn-Gly sequence to deamidation/isomerization remains a
      difficult task. This is especially true for proteins that are subjected to
      enzymatic digestion during their characterization, since the above transformation
      could occur spontaneously during this treatment. To address this issue, we
      applied a stable-isotope (18)O-labeling method combined with nano-LC-MS/MS to
      examine the susceptibility of two Asn-Gly sites in beta2-microglobulin (beta2m)
      to the reaction. The method permits the reaction occurring in a protein to be
      distinguished from that during enzymatic treatment. When beta2m was incubated for
      60 days at 37  degrees C, deamidation at Asn17-Gly and Asn42-Gly with half-lives
      of 33 and 347 days occurred, respectively. Moreover, a comparison of the
      deamidated products to synthetic peptides revealed that 44% of the Asp17 and 96%
      of the Asp42 had been converted into isoAsp forms. Interestingly, such
      structurally altered beta2m showed a specific affinity for divalent Cu(2+) ions,
      which is thought to be a candidate for initiating fibril formation.

PMID- 23126477
TI  - Editorial comment to robotic versus laparoscopic partial nephrectomy for tumor in
      a solitary kidney: a single institution comparative analysis.

PMID- 23126478
TI  - Outreach visits by clinical pharmacists improve screening for the metabolic
      syndrome among mentally ill patients.
AB  - BACKGROUND: Patients suffering from schizophrenia and affective disorder have an
      increased risk of the metabolic syndrome (MeS); hence identification of patients
      developing MeS may help preventing morbidity and mortality. AIMS: The aim of the
      study was to evaluate the effect of outreach visit by clinical pharmacists to
      support the implementation of screening of MeS at a psychiatric ward. METHODS:
      The study was conducted at the psychiatric ward, Odense University Hospital. In
      2008, clinical guidelines for systematic screening and prevention of metabolic
      risk were developed and implemented by passive dissemination (PD) followed by a
      period of active implementation (AI). AI contained outreach visits by clinical
      pharmacists on a weekly basis. Patients with affective disorder or schizophrenia
      were included. The study was designed as a before-and-after study, and electronic
      patient charts were used for assessment of adherence to the clinical guidelines.
      RESULTS: In total, 205 patients were included in the study (93 patients in the PD
      group, 112 patients in the AI group). A significant improvement of the use of the
      screening sheet from 36% in the PD group to 81% in the AI group was found (p <
      0.001). Consequently, the quality of the screening increased significantly
      resulting in 45% in the AI group being identified with MeS compared with 10% in
      the PD group (p < 0.001). CONCLUSION: The outreach visits by clinical pharmacists
      significantly improved the use of the screening sheet and resulted in a
      significant increase in the proportion of patients identified with MeS (p <
      0.001). CLINICAL IMPLICATIONS: The increase in the use of a screening sheet for
      MeS among patients admitted to a psychiatric ward as a result of outreach visits
      by clinical pharmacist improve assessment for MeS. This may lead to better
      identification of patients suffering from MeS and hence increase the possibility
      of treating MeS and preventing morbidity and mortaligy.

PMID- 23126479
TI  - There is no evidence for an association between the serotonin receptor 3A gene
      C178T polymorphism and tardive dyskinesia in Korean schizophrenia patients.
AB  - BACKGROUND: Tardive dyskinesia (TD) is a potential adverse effect of long-term
      treatment with antipsychotics. Previous studies have suggested a link between
      brain serotonergic systems and TD vulnerability. A recent report described that a
      serotonin 3 receptor (5-HTR3) agonist induced rhythmic movements in mice with
      complete paraplegia. Furthermore, it has been reported that the 5-HTR3 antagonist
      ondansetron is efficacious in the treatment of Gilles de la Tourette syndrome
      (GTS). AIM: The aim of the present study was to determine whether the 5-HTR3A
      gene C178T polymorphism is associated with antipsychotic-induced TD in Korean
      schizophrenia patients. METHODS: We investigated 280 Korean schizophrenia
      patients. Subjects with TD (n = 105) and without TD (n = 175) were matched for
      antipsychotic drug exposure and other relevant variables. RESULTS: The
      distributions of genotypic (chi-squared = 3.55, p = 0.169) and allelic (chi
      squared = 0.40, p = 0.528) frequencies did not differ between patients with and
      without TD. The total score on the Abnormal Involuntary Movement Scale also did
      not differ between the two genotype groups (F = 0.94, p = 0.391). CONCLUSIONS:
      The findings of the present study do not support the involvement of the 5-HTR3A
      gene C178T polymorphism in TD in Korean schizophrenia subjects.

PMID- 23126480
TI  - Associations between high levels of conduct problems and co-occurring problems
      among the youngest boys and girls in schools: a cross-sectional study.
AB  - BACKGROUND: Few studies have focused on conduct problems and co-occurring
      problems among the youngest children in schools, such as social, internalizing
      and attention problems. In particular, there is a lack of studies that
      differentiate between boys and girls in terms of such problems. AIM: The aim of
      the current study was to test associations between conduct problems and social,
      internalizing and attention problems, as well as adaptive school functioning,
      which was rated by the teachers of boys and girls in grades 1-3. METHODS: In a
      cross-sectional study, 103 boys and 108 girls in grades 1-3 at six schools
      participated in a national Norwegian study of child conduct problems in the
      normal population. Linear regression analysis was used to test the associations
      between conduct problems, social skills, problems of internalization, attention
      problems and adaptation to school among boys and girls. RESULTS: There were
      significant associations between high levels of conduct problems and social
      skills problems, attention problems and low adaptive school functioning scores
      among boys and girls. Attention problems had the most powerful associations with
      conduct problems for both genders. CONCLUSIONS: Young schoolchildren with high
      levels of conduct problems also had co-occurring problems. Schools and teachers
      need to adopt a comprehensive approach to help these children during their first
      years in school.

PMID- 23126481
TI  - Comorbidity of disruptive behavioral disorders and attention-deficit
      hyperactivity disorder--indicator of severity in problematic behavior?
AB  - BACKGROUND: Disruptive behavioral disorders (DBD) and attention-deficit
      hyperactivity disorder (ADHD) are both characterized by certain patterns of
      misbehavior among adolescents. AIMS: The aim of this study was to examine how the
      comorbidity of DBD and ADHD affects in misbehavior among adolescents. METHODS: A
      total of 158 adolescents aged 16-18 years, from a subsample of the Northern
      Finland Birth Cohort 1986 (NFBC 1986), were interviewed with the Finnish
      translation of the semi-structured Schedule for Affective Disorders and
      Schizophrenia for School-Age Children--Present and Lifetime (K-SADS-PL) in order
      to obtain DBD, including conduct disorder (CD) and oppositional defiant disorder
      (ODD), and ADHD diagnoses. The structure of the CD symptoms, obtained from the K
      SADS-PL, was compared with the previously formed model about the development of
      the problematic behavior. The severity of the CD symptoms was compared with
      adolescents diagnosed with only DBD, only ADHD and with both DBD and ADHD. Also,
      the associations with other psychiatric disorders diagnosed at age 16 were
      evaluated. RESULTS: The boys in the study sample were diagnosed with ADHD or with
      comorbid DBD and ADHD more often than girls. The severity of CD symptoms was
      statistically significantly associated with the comorbid DBD and ADHD group. The
      adolescents diagnosed with comorbid DBD and ADHD had an increased risk for
      anxiety disorders, depressive disorders and substance abuse disorders.
      CONCLUSIONS: The comorbidity of DBD and ADHD seems to indicate the severity of CD
      symptoms. CLINICAL IMPLICATIONS: The comorbidity between DBD and ADHD should be
      considered in clinical practice because it could indicate more serious
      problematic behavior than pure disorders alone.

PMID- 23126482
TI  - Interaction of tannins and other sorghum phenolic compounds with starch and
      effects on in vitro starch digestibility.
AB  - This study investigated interactions of sorghum proanthocyanidins (PAs) with
      starch molecules and the effect on in vitro starch digestibility. High tannin
      (predominant in PA), black (monomeric polyphenols), and white (low in
      polyphenols) sorghum phenolic extracts were mixed and cooked with starches
      varying in amylose content. Starch pasting properties, polyphenol profile, and
      resistant starch (RS) were determined. PAs decreased setback of normal starch and
      were least extractable after cooking with all starches. Pure amylose interacted
      more strongly with oligomeric and polymeric PA compared to amylopectin. The PA
      extract increased the net RS in normal starch by about 2 times more than the
      monomeric polyphenol extract; debranching amylopectin increased the difference by
      4.3 times. Only treatments with PA increased RS in high amylose starch (52%
      higher than the control). Sorghum PAs interact strongly with starch, decreasing
      starch digestibility. The interactions appear to be specific to amylose and
      linear fragments of amylopectin, suggesting hydrophobic interactions are
      involved.

PMID- 23126483
TI  - Enhancing self-protective behavior: efficacy beliefs and peer feedback in risk
      communication.
AB  - In times of a high-impact safety incident citizens may have a variety of sources
      available to help them cope with the situation. This research focuses on the
      interplay of efficacy information in risk communication messages and peer
      feedback, such as responses on social network sites (SNSs) in the context of a
      high-impact risk on the intention to engage in self-protective behavior. The
      study pitted high and low efficacy information messages against supporting and
      opposing peer feedback (N = 242). Results show a significant interaction effect
      between efficacy information in a news article and peer feedback from SNS
      messages on both the intention to engage in self-protective behavior and levels
      of involvement. Participants who received the article with more efficacy
      information and also received supportive peer feedback via SNS messages were more
      likely to express higher levels of involvement and greater intentions to engage
      in protective behavior. When confronted with a low efficacious news article, the
      effect of peer feedback on these two variables was significantly stronger.
      Finally, implications for theory and government risk communication are discussed.

PMID- 23126484
TI  - Carbohydrate utilization by enterohaemorrhagic Escherichia coli O157:H7 in bovine
      intestinal content.
AB  - The bovine gastrointestinal (GI) tract is the main reservoir for
      enterohaemorrhagic Escherichia coli (EHEC) responsible for food-borne infections.
      Characterization of nutrients preferentially used by EHEC in the bovine intestine
      would help to develop ecological strategies to reduce EHEC carriage. However, the
      carbon sources that support the growth of EHEC in the bovine intestine are poorly
      documented. In this study, a very low concentration of glucose, the most abundant
      monomer included in the cattle dietary polysaccharides, was detected in bovine
      small intestine contents (BSIC) collected from healthy cows at the
      slaughterhouse. Six carbohydrates reported to be included in the mucus layer
      covering the enterocytes [galactose, N-acetyl-glucosamine (GlcNAc), N-acetyl-
      galactosamine (GalNAc), fucose, mannose and N-acetyl neuraminic acid (Neu5Ac)]
      have been quantified for the first time in BSIC and accounted for a total
      concentration of 4.2 mM carbohydrates. The genes required for enzymatic
      degradation of the six mucus-derived carbohydrates are highly expressed during
      the exponential growth of the EHEC strain O157:H7 EDL933 in BSIC and are more
      strongly induced in EHEC than in bovine commensal E. coli. In addition, EDL933
      consumed the free monosaccharides present in the BSIC more rapidly than the
      resident microbiota and commensal E. coli, indicating a competitive ability of
      EHEC to catabolize mucus-derived carbohydrates in the bovine gut. Mutations of
      EDL933 genes required for the catabolism of each of these sugars have been
      constructed, and growth competitions of the mutants with the wild-type strain
      clearly demonstrated that mannose, GlcNAc, Neu5Ac and galactose catabolism
      confers a high competitive growth advantage to EHEC in BSIC and probably
      represents an ecological niche for EHEC strains in the bovine small intestine.
      The utilization of these mucus-derived monosaccharides by EDL933 is apparently
      required for rapid growth of EHEC in BSIC, and for maintaining a competitive
      growth rate as compared with that of commensal E. coli. The results suggest a
      strategy for O157:H7 E. coli survival in the bovine intestine, whereby EHEC
      rapidly consumes mucus-derived carbohydrates that are poorly consumed by bacteria
      belonging to the resident intestinal microbiota, including commensal E. coli.

PMID- 23126485
TI  - What do we know when we know a person across contexts? Examining self-concept
      differentiation at the three levels of personality.
AB  - OBJECTIVE: Previous research examining self-concept differentiation (SCD) has
      been characterized by (a) a focus on behavioral traits and (b) the conflation of
      mean-level and inter-contextual differentiation. In two studies, we considered
      non-conflated measures of SCD at the three levels of personality description in
      relation to adjustment. METHOD: In Study 1, participants completed measures of
      adjustment, rated their behavioral tendencies (dispositional traits), produced a
      list of goals (characteristic adaptations), and recalled a self-defining memory
      (life narratives), from within professional and personal domains. In Study 2, the
      procedure was modified: Participants reporting either low or high levels of
      adjustment subsequently rated their behavioral traits, provided a list of goals,
      or produced a self-defining memory, from five contexts. RESULTS: In Study 1,
      adjustment related positively to SCD at the level of characteristic adaptations
      but negatively to SCD at the level of life narratives. In Study 2, well-adjusted
      participants exhibited a greater degree of SCD at the level of characteristic
      adaptations but a greater degree of thematic consistency at the level of life
      narratives, relative to those low in adjustment. CONCLUSIONS: These results
      highlight the dynamic nature of SCD across levels of personality and align with
      the notion that differentiation represents virtue and vice.

PMID- 23126486
TI  - An experimental and computational assessment of acid-catalyzed azide-nitrile
      cycloadditions.
AB  - The mechanism of the azide-nitrile cycloaddition mediated by different Bronsted
      and Lewis acids has been addressed through DFT calculations. In all cases
      activation of the nitrile substrate by the Bronsted or Lewis acid catalyst was
      found to be responsible for the rate enhancement. According to DFT calculations
      the cycloaddition proceeds in a stepwise fashion involving the initial formation
      of an open-chain imidoyl azide intermediate. Kinetic experiments performed using
      N-methyl-2-pyrrolidone as solvent and sodium azide as azide source demonstrate
      that all evaluated Bronsted acids have the same efficiency toward cycloaddition
      with benzonitrile, suggesting that hydrazoic acid is the actual dominant
      catalytic species in these tetrazole syntheses. Lewis acids such as Zn or Al
      salts perform in a similar manner, activating the nitrile moiety and leading to
      an open-chain intermediate that subsequently cyclizes to produce the tetrazole
      nucleus. The most efficient catalyst evaluated was 5-azido-1-methyl-3,4-dihydro
      2H-pyrrolium azide, which can readily be generated in situ from aluminum
      chloride, sodium azide in N-methyl-2-pyrrolidone. The efficiency of this catalyst
      has been examined by preparation of a series of 5-substituted-1H-tetrazoles. The
      desired tetrazole structures were obtained in high yields within 3-10 min
      employing controlled microwave heating.

PMID- 23126487
TI  - Does cerclage improve neonatal outcomes in a molar pregnancy and a coexistent
      fetus? A case report.
AB  - BACKGROUND: Complete hydatiform mole and coexistent viable fetus is very rare.
      The use of a cervical cerclage for cervical indications in the presence of this
      condition has never been reported. Although the diagnosis was made postnatal, the
      objective is to present a case with good neonatal outcome. CASE PRESENTATION: A
      patient presented with vaginal spotting around 23 weeks. She has a history of
      four preterm deliveries. Her cervix was dilated and a cerclage was placed. She
      presented again with PPROM around 25 weeks. She went into spontaneous preterm
      labor and delivered a viable fetus that is a healthy girl today. Eventually the
      pathology of the placenta showed a complete hydatidiform mole. CONCLUSION: It is
      necessary to inform patients about the potential risks and poor outcomes of this
      condition. For those who desire all potential interventions, cerclage placement
      could be considered.

PMID- 23126488
TI  - A nude mouse model of hypertrophic scar shows morphologic and histologic
      characteristics of human hypertrophic scar.
AB  - Hypertrophic scar (HSc) is a fibroproliferative disorder that occurs following
      deep dermal injury. Lack of a relevant animal model is one barrier toward better
      understanding its pathophysiology. Our objective is to demonstrate that grafting
      split-thickness human skin onto nude mice results in survival of engrafted human
      skin and murine scars that are morphologically, histologically, and
      immunohistochemically consistent with human HSc. Twenty nude mice were
      xenografted with split-thickness human skin. Animals were euthanized at 30, 60,
      120, and 180 days postoperatively. Eighteen controls were autografted with full
      thickness nude mouse skin and euthanized at 30 and 60 days postoperatively. Scar
      biopsies were harvested at each time point. Blinded scar assessment was performed
      using a modified Manchester Scar Scale. Histologic analysis included hematoxylin
      and eosin, Masson's trichrome, toluidine blue, and picrosirius red staining.
      Immunohistochemistry included anti-human human leukocyte antigen-ABC, alpha
      smooth muscle actin, decorin, and biglycan staining. Xenografted mice developed
      red, shiny, elevated scars similar to human HSc and supported by blinded scar
      assessment. Autograft controls appeared morphologically and histologically
      similar to normal skin. Xenografts survived up to 180 days and showed increased
      thickness, loss of hair follicles, adnexal structures and rete pegs,
      hypercellularity, whorled collagen fibers parallel to the surface,
      myofibroblasts, decreased decorin and increased biglycan expression, and
      increased mast cell density. Grafting split-thickness human skin onto nude mice
      results in persistent scars that show morphologic, histologic, and
      immunohistochemical consistency with human HSc. Therefore, this model provides a
      promising technique to study HSc formation and to test novel treatment options.

PMID- 23126490
TI  - Neurocognitive profiles in children with epilepsy.
AB  - PURPOSE: The presence of specific neurocognitive deficits may help explain why
      school achievement and psychosocial functioning are often worse in children with
      epilepsy than would be predicted by their global intellectual functioning. This
      study compared children with two forms of epilepsy: localization-related epilepsy
      with complex partial seizures (CPS) and childhood absence epilepsy (CAE), to
      determine whether they display distinct neurocognitive profiles. METHODS: Fifty
      one children with CPS, 31 children with CAE, and 51 controls underwent
      neuropsychological testing assessing verbal memory, visual memory, and executive
      functioning. Groups were compared in these cognitive domains. Within-group
      analyses were also conducted to examine seizure-related factors that may be
      related to neuropsychological test performance. KEY FINDINGS: When compared to
      controls, children with CPS showed a mild generalized cognitive deficit, whereas
      children with CAE did not. When we controlled for intelligent quotient (IQ), both
      epilepsy groups showed poorer performance relative to controls in the domain of
      verbal memory. When the epilepsy groups were compared to one another, the CPS
      group performed significantly poorer than the CAE group on a test of generalized
      cognitive functioning. However, in the specific domains of executive functioning,
      verbal memory, and visual memory the epilepsy groups did not differ when compared
      to one another. SIGNIFICANCE: Neurocognitive deficits present in the context of
      grossly intact global intellectual functioning highlight the importance of
      neuropsychological screening in both children with CPS and children with CAE.

PMID- 23126491
TI  - Polymer triplet energy levels need not limit photocurrent collection in organic
      solar cells.
AB  - We study charge recombination via triplet excited states in donor/acceptor
      organic solar cells and find that, contrary to intuition, high internal quantum
      efficiency (IQE) can be obtained in polymer/fullerene blend devices even when the
      polymer triplet state is significantly lower in energy than the intermolecular
      charge transfer (CT) state. Our model donor system comprises the copolymer PIDT
      PhanQ: poly(indacenodithiophene-co-phenanthro[9,10-b]quinoxaline), which when
      blended with phenyl-C(71)-butyric acid methyl ester (PC(71)BM) is capable of
      achieving power conversion efficiencies of 6.0% and IQE ~ 90%, despite the fact
      that the polymer triplet state lies 300 meV below the interfacial CT state.
      However, as we push the open circuit voltage (V(OC)) higher by tailoring the
      fullerene reduction potential, we observe signatures of a new recombination loss
      process near V(OC) = 1.0 V that we do not observe for PCBM-based devices. Using
      photoinduced absorption and photoluminescence spectroscopy, we show that a new
      recombination path opens via the fullerene triplet manifold as the energy of the
      lowest CT state approaches the energy of the fullerene triplet. This pathway
      appears active even in cases where direct recombination via the polymer triplet
      remains thermodynamically accessible. These results suggest that kinetics, as
      opposed to thermodynamics, can dominate recombination via triplet excitons in
      these blends and that optimization of charge separation and kinetic suppression
      of charge recombination may be fruitful paths for the next generation of
      panchromatic organic solar cell materials with high V(OC) and J(SC).

PMID- 23126492
TI  - The antimicrobial effect of apical box versus apical cone preparation using
      iodine potassium iodide as root canal dressing: a pilot study.
AB  - PURPOSE: The purpose was to study the reduction of intra-canal microflora in
      premolars with apical periodontitis instrumented with either apical box or apical
      cone preparation and to provide measurements of intervention effects to allow
      proper power calculation in future clinical trials. METHODS: Twenty-four patients
      were centrally randomized to apical box preparation (size #60) or cone
      preparation (apical size #25). The groups were comparable regarding the presence
      of primary caries and type of coronal restoration. In the course of canal
      preparation each tooth was irrigated with 2.5% NaOCl (12 ml). Lastly, the canals
      were filled with 17% EDTA (2 * 30 s) and 5% iodine potassium iodide (IKI) for 10
      min. The canals were sampled for micro-organisms on four occasions: before
      instrumentation, after instrumentation, after application of IKI dressing and at
      the beginning of the second appointment 1 week later. Between the treatment
      sessions, the root canals were sealed with IRM cement. In the laboratory, culture
      techniques were used to measure microbial growth, which was classified as: none,
      very sparse, sparse, moderate, heavy or very heavy. RESULTS: Initially, microbes
      were recovered in 88% of the teeth. Growth was classified as none in 35% of the
      teeth after instrumentation and in 50% after the application of IKI. Irrespective
      of the time of sampling, no significant difference in microbial growth reduction
      was observed between the two types of apical preparation. Based on the 1-week
      post-sampling, a power calculation revealed that over 900 patients are needed to
      show a difference of 9% between the two protocols tested. CONCLUSIONS: Future
      trials should be conducted using stringent protocols and as multi-centre trials
      for reaching the required information size.

PMID- 23126494
TI  - Differences in onset of disease and severity of psychopathology between
      toxoplasmosis-related and toxoplasmosis-unrelated schizophrenia.
AB  - OBJECTIVE: Toxoplasmosis is a lifelong parasitic disease that appears to be
      associated to schizophrenia. However, no distinguishing attributes in Toxoplasma
      infected schizophrenia patients have been described as yet. METHOD: We searched
      for differences in symptom profile, cognitive performance and treatment response
      between 194 Toxoplasma-free and 57 (22.7%) Toxoplasma-infected schizophrenia
      patients treated in Prague Psychiatric Centre between 2000 and 2010. RESULTS:
      Infected and non-infected patients differed in severity of symptoms (P = 0.032)
      measured with the Positive and Negative Symptom Scale (PANSS). Infected patients
      scored higher in positive subscale of PANSS, but not in the general and negative
      subscales. Infected men scored higher also in Total PANSS score, and negative,
      reality distortion, disorganisation and cognitive scores. Higher PANSS scores of
      positive, negative and disorganised psychopathology were associated with the
      lower titres of anti-Toxoplasma antibodies suggesting that psychopathology
      deteriorates with duration of parasitic infection. Infected patients remained
      about 33 days longer in hospital during their last admission than uninfected ones
      (P = 0.003). Schizophrenia started approximately 1 year earlier in infected men
      and about 3 years later in infected women, no such difference was observed in
      uninfected subjects. CONCLUSION: Latent toxoplasmosis in schizophrenia may lead
      to more severe positive psychopathology and perhaps less favourable course of
      schizophrenia.

PMID- 23126493
TI  - Ameliorative effects of 7-methylcoumarin and 7-methoxycoumarin against CCl4
      induced hepatotoxicity in rats.
AB  - The available conventional remedies for the treatment of drug-induced liver
      diseases are highly inadequate and possess serious adverse effects; therefore,
      the development of new, effective drugs is considered necessary. This article
      explores the hepatoprotective and antioxidant potential of 7-methylcoumarin (MC)
      and 7-methoxycoumarin (MOC) in CCl(4)-induced hepatotoxicity in rats. MC and MOC
      individually, at doses of 50 and 100 mg/kg body weight, were administered orally
      once-daily for 7 days. The hepatoprotective activity was assessed using various
      biochemical parameters, such as alanine aminotransferase (ALT), aspartate
      aminotransferase (AST), serum bilirubin (TB), total protein (TP), and albumin
      (TA). Serum antioxidant enzyme [e.g., superoxide dismutase (SOD) and catalase
      (CAT)] levels were determined. Also, thiobarbituric-acid-related substances
      (TBARS) levels, along with histopathological studies of liver tissue, were
      scrutinized. Pretreatment with MC and MOC significantly decreased ALT, AST, and
      TB in the serum of CCl(4)-induced liver damaged rats in a dose-dependent manner.
      TA and TP levels in the serum were also restored significantly in all
      presupplemented MC and MOC groups. In addition, oxidative stress induced by
      CCl(4) was prevented significantly; thereby, increasing SOD and CAT levels and
      decreasing TBARS levels in liver homogenates. Histopathological studies revealed
      the ameliorative natures of both the compounds. This study demonstrates the
      strong hepatoprotective activity of MC and MOC, which could be attributed to
      their potent antioxidant effects.

PMID- 23126495
TI  - Bioactive constituents of Salvia chrysophylla Stapf.
AB  - The dichloromethane extract of the aerial parts of Salvia chrysophylla Stapf
      (Lamiaceae), which is an endemic species to south-western Anatolia, was studied
      for non-volatile secondary metabolites for the first time in this study.
      Structures of the isolated compounds were elucidated as sclareol, beta
      sitosterol, salvigenin, oleanolic acid and ursolic acid. The lipid peroxidation
      inhibitory activity and the DPPH free radical scavenging activity of the pure
      isolates were investigated to establish their antioxidant potential. Their
      anticholinesterase activity was carried out by the Ellman assay against both
      enzymes, acetylcholinesterase (AChE) and butyrylcholinesterase, and diterpene
      sclareol exhibited fairly good activity against both the enzymes while the two
      triterpenoids oleanolic and ursolic acids exhibited selective activity against
      AChE.

PMID- 23126497
TI  - cIAP1/2 negatively regulate RANKL-induced osteoclastogenesis through the
      inhibition of NFATc1 expression.
AB  - Receptor activator of nuclear factor kappaB (RANK) is a member of the tumor
      necrosis factor receptor superfamily (TNFRSF) and triggers osteoclastogenesis by
      inducing the expression of NFATc1 through the activation of the NF-kappaB and
      MAPK pathways. Cellular inhibitors of apoptosis proteins 1 and 2 (cIAP1/2), which
      are ubiquitin E3 ligases, are involved in the activation of the NF-kappaB and
      MAPK pathways by various members of the TNFRSF. However, the involvement of
      cIAP1/2 in RANK signaling has remained largely unknown. In this study, we reveal
      the involvement of cIAP1/2 in RANK ligand (RANKL)-induced osteoclastogenesis. The
      over-expression of cIAP1 or cIAP2 in the mouse monocytic cell line Raw264.7
      resulted in the significant suppression of RANKL-induced NFATc1 mRNA expression
      and osteoclastogenesis, whereas the activation of the NF-kappaB and MAPK pathways
      was barely changed by these over-expressions. The depletion of endogenous cIAP1/2
      by their specific inhibitor MV1 or their siRNA-mediated knockdown resulted in
      enhanced RANKL-induced NFATc1 expression and osteoclastogenesis without affecting
      the activation of the NF-kappaB and MAPK pathways. In combination, these results
      indicate that cIAP1/2 negatively regulate osteoclastogenesis by inhibiting NFATc1
      mRNA expression in a manner that is distinct from the previously identified
      functions of cIAP1/2.

PMID- 23126498
TI  - An epidemiologic study on anthropometric dimensions of 7-11-year-old Iranian
      children: considering ethnic differences.
AB  - Anthropometric data can be used to identify the physical dimensions of equipment,
      furniture, clothing and workstations. The use of poorly designed furniture that
      fails to fulfil the users' anthropometric dimensions, has a negative impact on
      human health. In this study, we measured some anthropometric dimensions of
      Iranian children from different ethnicities. A total of 12,731 Iranian primary
      school children aged 7-11 years were included in the study and their static
      anthropometric dimensions were measured. Descriptive statistics such as mean,
      standard deviation and key percentiles were calculated. All dimensions were
      compared among different ethnicities and different genders. This study showed
      significant differences in a set of 22 anthropometric dimensions with regard to
      gender, age and ethnicity. Turk boys and Arab girls were larger than their
      contemporaries in different ages. According to the results of this study,
      difference between genders and among different ethnicities should be taken into
      account by designers and manufacturers of school furniture. PRACTITIONER SUMMARY:
      In this study, we measured 22 static anthropometric dimensions of 12,731 Iranian
      primary school children aged 7-11 years from different ethnicities. Descriptive
      statistics such as mean, standard deviation and key percentiles were measured for
      each dimension. This study showed significant differences in a set of 22
      anthropometric dimensions in different genders, ages and ethnicities.

PMID- 23126496
TI  - Association between body size and blood pressure in children from different
      ethnic origins.
AB  - OBJECTIVE: To assess associations between body size and blood pressure in
      children (5-6 years) from different ethnic origins. METHOD: Five ethnic groups of
      the ABCD cohort were examined: Dutch (n=1 923), Turkish (n=99), Moroccan (n=187),
      Black-African (n=67) and Black-Caribbean (n=121). Data on body-mass-index (BMI),
      waist-to-height ratio (WHtR), fat-mass-index (FMI), and systolic blood pressure
      (SBP) and diastolic blood pressure (DBP), were collected. Linear regression
      analysis with restricted cubic splines was used to examine non-linear
      associations between body size and blood pressure, adjusted for age, sex, height
      and birth weight. RESULTS: Ethnic differences were found in associations of BMI
      with SBP and DBP (SBP: p=0.001 and DBP: p=0.01) and FMI with SBP (p=0.03). BMI
      and FMI had a relatively large positive association with SBP in Turkish children
      (BMI: beta=2.46mmHg; 95%CI:1.20-3.72; FMI: beta=2.41mmHg; 95%CI:1.09-3.73)
      compared to Dutch (BMI: beta=1.31mmHg; 95%CI:0.71-1.92; FMI: beta=0.84mmHg;
      95%CI:0.23-1.45). Black-Caribbean and Moroccan children showed high blood
      pressure with low BMI and FMI. Moroccan children showed higher SBP with high BMI
      and FMI. WHtR was positively associated with SBP and DBP, similar in all ethnic
      groups. Generally, strongest associations with blood pressure were found for BMI
      in all ethnic groups. CONCLUSION: Ethnic-specific associations between BMI, and
      FMI and blood pressure are present at young age, with Turkish children showing
      the highest increase in blood pressure with increasing body size. The higher
      blood pressure in the Black-Caribbean and Moroccan children with low BMI needs
      further research. WHtR or FMI do not seem to be associated more strongly to blood
      pressure than BMI in any ethnic group.

PMID- 23126499
TI  - PAnalyzer: a software tool for protein inference in shotgun proteomics.
AB  - BACKGROUND: Protein inference from peptide identifications in shotgun proteomics
      must deal with ambiguities that arise due to the presence of peptides shared
      between different proteins, which is common in higher eukaryotes. Recently data
      independent acquisition (DIA) approaches have emerged as an alternative to the
      traditional data dependent acquisition (DDA) in shotgun proteomics experiments.
      MSE is the term used to name one of the DIA approaches used in QTOF instruments.
      MSE data require specialized software to process acquired spectra and to perform
      peptide and protein identifications. However the software available at the moment
      does not group the identified proteins in a transparent way by taking into
      account peptide evidence categories. Furthermore the inspection, comparison and
      report of the obtained results require tedious manual intervention. Here we
      report a software tool to address these limitations for MSE data. RESULTS: In
      this paper we present PAnalyzer, a software tool focused on the protein inference
      process of shotgun proteomics. Our approach considers all the identified proteins
      and groups them when necessary indicating their confidence using different
      evidence categories. PAnalyzer can read protein identification files in the XML
      output format of the ProteinLynx Global Server (PLGS) software provided by Waters
      Corporation for their MSE data, and also in the mzIdentML format recently
      standardized by HUPO-PSI. Multiple files can also be read simultaneously and are
      considered as technical replicates. Results are saved to CSV, HTML and mzIdentML
      (in the case of a single mzIdentML input file) files. An MSE analysis of a real
      sample is presented to compare the results of PAnalyzer and ProteinLynx Global
      Server. CONCLUSIONS: We present a software tool to deal with the ambiguities that
      arise in the protein inference process. Key contributions are support for MSE
      data analysis by ProteinLynx Global Server and technical replicates integration.
      PAnalyzer is an easy to use multiplatform and free software tool.

PMID- 23126500
TI  - Brain meningioma in a patient with complaints of low back pain and leg weakness.
AB  - BACKGROUND: Meningiomas are the most common form of benign brain tumors in
      adults. Due to a wide range of symptom presentation, tumors can be difficult to
      diagnose. For physical therapists, it is important to be aware that brain tumors
      can mimic other diagnoses and present in conjunction with other musculoskeletal
      disorders. The purpose of this case report is to describe the physical
      therapists' management of a patient who presented with initial signs and symptoms
      of low back pain (LBP) and radicular symptoms, but whose symptoms became atypical
      and required further diagnostic work-up and medical management. DIAGNOSIS: The
      patient was ultimately diagnosed with a large, benign meningioma in the left
      motor cortex of the brain. One week following referral from the physical
      therapist, the tumor was surgically excised. DISCUSSION: This case report brings
      attention to the importance of regular, systematic examination of the patient's
      clinical presentation to identify mechanical and non-mechanical signs and
      symptoms and make the appropriate medical referral.

PMID- 23126501
TI  - Guillain-Barre syndrome patient's satisfaction with physiotherapy: A two-part
      observational study.
AB  - The purpose of this observational study was to assess Guillain-Barre' syndrome
      (GBS) patients' satisfaction with physiotherapy in the acute and sub-acute
      setting, and provide an overview of inpatient case management, including the
      number of complications. Twenty-seven patients admitted to Sir Charles Gairdner
      Hospital (SCGH) with GBS between 1 May 2005 and 30 April 2010 were considered for
      inclusion. Nineteen patients consented and a waiver of consent was granted for
      four other patients. Data were collected from case-note audit (n = 23) and
      telephone survey (n = 19) during June and July 2011. Participants receiving
      physiotherapy (n = 16) reported they were satisfied with management (87%),
      treatment frequency (88%), duration (94%), and timetabling (81%) of treatment and
      the professionalism and rapport (100%) of physiotherapists. Median length of
      hospital stay was 20 days (range 5-198) for 23 participants. Physiotherapists
      documented patient assessment within 2 days from admission (range 1-5). First
      functional improvements were documented on day 6 (median, range 2-34).
      Physiotherapists were most commonly first to mobilize patients to sit, stand,
      transfer, and walk (83%, 82%, 81%, and 90%, respectively). Twenty patients (87%)
      developed complications during their hospital stay, the most common being low
      back pain (61%). This study has demonstrated that GBS patients were satisfied
      with care provided by physiotherapy.

PMID- 23126502
TI  - 1,25-dihydroxyvitamin D3 inhibits nuclear factor kappa B activation by
      stabilizing inhibitor IkappaBalpha via mRNA stability and reduced phosphorylation
      in passively sensitized human airway smooth muscle cells.
AB  - Excessive activation of nuclear transcription factor-kappaB (NF-kappaB) is
      involved in human airway smooth muscle cells (HASMCs) activities in asthma. We
      investigated the effects of 1,25 - dihydroxyvitamin D3 [1,25 - (OH) 2D3] on the
      NF- kappaB signaling pathway in passively sensitized HASMCs and the molecular
      mechanisms involved. HASMCs were treated with either healthy controls' serum,
      asthma patients' serum or pretreated with 1,25 - (OH) 2D3 prior to treatment with
      asthmatics' serum. At 1 h after serum treatment: electrophoretic mobility shift
      assay (EMSA) was used to detect NF-kappaB DNA binding activity;
      immunocytochemical staining was used to observe the nuclear translocation of NF
      kappaB p65; Western blots were used for NF-kappaB p65, IkappaBalpha, and phospho
      IkappaBalpha protein levels and the nuclear translocation of NF-kappaB p65; real
      time quantitative PCR was used for NF-kappaB p65 and IkappaBalpha mRNA
      expressions; and actinomycin D treatment was used to determine IkappaBalpha mRNA
      stability. Our major findings were: (1) 1,25 - (OH) 2D3 significantly reduced
      asthma serum passively sensitized HASMCs NF-kappaB DNA binding activity and
      inhibited the nuclear translocation of NF-kappaB p65; (2) 1,25 - (OH) 2D3
      increased the stability of IkappaBalpha mRNA with reduced IkappaBalpha
      phosphorylation in asthma serum passively sensitized HASMCs and significantly
      increased IkappaBalpha expression in these HASMCs. Inhibiting NF-kappaB
      signalling with 1,25 - dihydroxyvitamin D3 may be a therapeutic approach for
      controlling HASMC-related remodelling in asthma.

PMID- 23126503
TI  - Comparative binding effects of aspirin and anti-inflammatory Cu complex in the
      active site of LOX-1.
AB  - (1)H NMR Saturation Transfer Difference (STD) experiments were applied to study
      the binding of aspirin and of an anti-inflammatory complex of Cu(I), namely
      [Cu(tpp)(pmt)](2) [pmt = 2-mercaptopyrimidine), synthesized in an attempt to
      develop novel metallotherapeutic molecules. While aspirin showed only very weak
      binding, the complex [Cu(tpp)(pmt)](2) clearly favored binding to LOX-1. In
      silico docking experiments in LOX-1 showed that aspirin does only weakly bind to
      LOX-1, while the complex binds with high affinity. In addition, docking
      experiments and molecular dynamics (MD) simulations showed that the complex binds
      via hydrogen bonding (HB), to an allosteric site of LOX-1, revealing that this
      enzyme has more than one accessible site for complex metallotherapeutic
      molecules. When aspirin was added in the solution containing LOX and the complex
      [Cu(tpp)(pmt)](2), the former was shown to hinder the binding of the Cu complex
      significantly. This may be interpreted as the copper complex aiding the transfer
      of aspirin through an acid-base reaction at the LOX enzyme which subsequently
      blocks its binding.

PMID- 23126505
TI  - Reduced dimensionality (4,3)D-HN(C)NH for rapid assignment of 1H(N)-15N HSQC
      peaks in proteins: an analytical tool for protein folding, proteomics, and drug
      discovery programs.
AB  - While nuclear magnetic resonance (NMR) has had commendable success in atomic
      level investigation of folded proteins, intrinsically unfolded and partially
      folded proteins have always posed a great challenge, because of poor chemical
      shift dispersions. We present here a reduced-dimensionality-based NMR triple
      resonance pulse sequence, (4,3)D-HN(C)NH, which not only helps to disperse the
      peaks further by combining (15)N and amide (1)H chemical shifts, but also
      directly establishes correlations between (1)H(i)(N), (15)N(i), (1)H(i+1)(N), and
      (15)N(i+1) spins along the F(1)-F(3) planes. The F(2)-F(3) projection planes of
      this experiment provide unique identification of the check points in amide
      resonances. An assignment strategy derived by combining information along the
      F(1)-F(3) planes and in the F(2)-F(3) projection planes of the experiment has
      been presented and shown to be very useful for both intrinsically
      disordered/unfolded proteins and folded protein alike. The experiment and the
      protocol would be valuable for protein folding, proteomics, and drug discovery
      programs.

PMID- 23126504
TI  - Cholera risk factors, Papua New Guinea, 2010.
AB  - BACKGROUND: Cholera is newly emergent in Papua New Guinea but may soon become
      endemic. Identifying the risk factors for cholera provides evidence for targeted
      prevention and control measures. METHODS: We conducted a hospital-based case
      control study to identify cholera risk factors. Using stool culture as the
      standard, we evaluated a cholera point of care test in the field. RESULTS: 176
      participants were recruited: 54 cases and 122 controls. Independent risk factors
      for cholera were: being over 20 years of age (aOR 2.5; 95%CI 1.1, 5.4),
      defecating in the open air (or river) (aOR 4.5; 95% CI 1.4, 14.4) and knowing
      someone who travelled to a cholera affected area (aOR 4.1; 95%CI 1.6, 10.7);
      while the availability of soap for handwashing at home was protective (aOR 0.41;
      95%CI 0.19, 0.87). Those reporting access to a piped water distribution system in
      the home were twice as likely to report the availability of soap for handwashing.
      The sensitivity and specificity of the rapid test were 72% (95% CI 47-90) and 71%
      (95%CI 44-90%). CONCLUSIONS: Improving population access to the piped water
      distribution system and sanitation will likely reduce transmission by enabling
      enhanced hygiene and limiting the contamination of water sources. The One step V.
      cholerae O1/O139 Antigen Test is of limited utility for clinical decision making
      in a hospital setting with access to traditional laboratory methods. Settlement
      dwellers and mobile populations of all age groups should be targeted for
      interventions in Papua New Guinea.

PMID- 23126506
TI  - Enhanced angiogenesis and relaxation of bladder as early response to bladder
      outlet obstruction.
AB  - OBJECTIVES: To provide insights into the pathogenesis of bladder insult secondary
      to bladder outlet obstruction. METHODS: Six-week-old female Sprague-Dawley rats
      (n = 80) were divided into eight groups, 10 rats each, according to the duration
      of bladder outlet obstruction, including 0, 3, 6, 12, 24, 48, 72 h and 1 week.
      Cystometric parameters were evaluated at 72 h and 1 week after bladder outlet
      obstruction. Bladder tissues were harvested and Masson's trichrome staining was
      carried out. Each slide was inspected microscopically and the mean percent
      collagen area was examined. Changes of collagen deposition and pathological
      expression of several factors including hypoxia inducible factor-1alpha, vascular
      endothelial growth factor, transforming growth factor-beta1 and nitric oxide
      synthase messenger ribonucleic acid of bladders were evaluated. RESULTS: A
      significant time-dependent increase in the bladder weight after 6 h and the
      percent of collagen area after 24 h of bladder outlet obstruction were found.
      Increase in hypoxia inducible factor-1alpha, transforming growth factor-beta1,
      inducible nitric oxide synthase messenger ribonucleic acid expression, time
      dependent increase in vascular endothelial growth factor, neuronal nitric oxide
      synthase and endothelial nitric oxide synthase messenger ribonucleic acid
      expression after 6 h of bladder outlet obstruction was found. The
      intercontraction interval decreased significantly after 72 h of bladder outlet
      obstruction. CONCLUSIONS: Cellular remodeling in the bladder secondary to bladder
      outlet obstruction starts in the early hours and it includes enhanced
      angiogenesis and bladder relaxation. Early relief from bladder outlet obstruction
      is helpful to preserve bladder structure and function.

PMID- 23126507
TI  - Avoidance goal pursuit depletes self-regulatory resources.
AB  - OBJECTIVE: Research on the strength model of self-regulation is burgeoning, but
      little empirical work has focused on the link between distinct types of daily
      goal pursuit and the depletion of self-regulatory resources. The authors
      conducted two studies on the link between avoidance goals and resource depletion.
      METHOD: Study 1 (283 [228 female] Caucasians, ages 18-51) investigated the
      concurrent and longitudinal relations between avoidance goals and resource
      depletion over a 1-month period. Study 2 (132 [93 female] Caucasians, ages 18-49)
      investigated the concurrent and longitudinal relations between avoidance goals
      and resource depletion over a 1-month period and explored resource depletion as a
      mediator of the avoidance goal to subjective well-being relation. RESULTS:
      Studies 1 and 2 documented both a concurrent and a longitudinal negative
      relationship between avoidance goals and self-regulatory resources, and Study 2
      additionally showed that self-regulatory resources mediate the negative link
      between avoidance goals and subjective well-being. Ancillary analyses
      demonstrated that the results observed in the two studies were independent of
      neuroticism. CONCLUSIONS: These findings advance knowledge in both the resource
      depletion and avoidance goal literatures, and bolster the view that avoidance
      goal pursuit over time represents a self-regulatory vulnerability.

PMID- 23126508
TI  - Bacterial and archaeal diversities in Yunnan and Tibetan hot springs, China.
AB  - Thousands of hot springs are located in the north-eastern part of the Yunnan
      Tibet geothermal zone, which is one of the most active geothermal areas in the
      world. However, a comprehensive and detailed understanding of microbial diversity
      in these hot springs is still lacking. In this study, bacterial and archaeal
      diversities were investigated in 16 hot springs (pH 3.2-8.6; temperature 47-96
      degrees C) in Yunnan Province and Tibet, China by using a barcoded 16S rRNA gene
      pyrosequencing approach. Aquificae, Proteobacteria, Firmicutes, Deinococcus
      Thermus and Bacteroidetes comprised the large portion of the bacterial
      communities in acidic hot springs. Non-acidic hot springs harboured more and
      variable bacterial phyla than acidic springs. Desulfurococcales and unclassified
      Crenarchaeota were the dominated groups in archaeal populations from most of the
      non-acidic hot springs; whereas, the archaeal community structure in acidic hot
      springs was simpler and characterized by Sulfolobales and Thermoplasmata. The
      phylogenetic analyses showed that Aquificae and Crenarchaeota were predominant in
      the investigated springs and possessed many phylogenetic lineages that have never
      been detected in other hot springs in the world. Thus findings from this study
      significantly improve our understanding of microbial diversity in terrestrial hot
      springs.

PMID- 23126509
TI  - Switching the stereochemical outcome of 6-endo-trig cyclizations; synthesis of
      2,6-cis-6-substituted 4-oxopipecolic acids.
AB  - A base-mediated 6-endo-trig cyclization of readily accessible enone-derived alpha
      amino acids has been developed for the direct synthesis of novel 2,6-cis-6
      substituted-4-oxo-L-pipecolic acids. A range of aliphatic and aryl side chains
      were tolerated by this mild procedure to give the target compounds in good
      overall yields. Molecular modeling of the 6-endo-trig cyclization allowed some
      insight as to how these compounds were formed, with the enolate intermediate
      generated via an equilibrium process, followed by irreversible
      tautomerization/neutralization providing the driving force for product formation.
      Stereoselective reduction and deprotection of the resulting 2,6-cis-6-substituted
      4-oxo-l-pipecolic acids to the corresponding 4-hydroxy-L-pipecolic acids was also
      performed.

PMID- 23126510
TI  - The patient protection and affordable care act: implications for geriatric nurses
      and patients.

PMID- 23126512
TI  - A note about endnotes.

PMID- 23126514
TI  - Evidence-based practice guideline: oral hygiene care for functionally dependent
      and cognitively impaired older adults.

PMID- 23126516
TI  - Topical application of a film-forming emulgel dressing that controls the release
      of stratifin and acetylsalicylic acid and improves/prevents hypertrophic
      scarring.
AB  - Here, we evaluate the efficacy of an emulgel dressing to control the release of
      an antifibrogenic factor, stratifin (SFN), along with an anti-inflammatory drug,
      acetylsalicylic acid (ASA), to be used as a wound dressing with hypertrophic scar
      reducing features. Emulgel dressings were prepared by dispersing positively
      charged submicron vesicles in carboxymethyl cellulose gel. Release kinetics of
      SFN/ASA and toxicity for primary skin cells were assessed in vitro.
      Antifibrogenic efficacy of medicated emulgel dressings was tested on a rabbit ear
      fibrotic model. Following topical application on the wounds, emulgels formed an
      occlusive film and controlled the release of SFN and ASA for 7 and 24 hours,
      respectively. Wounds treated with SFN/ASA-containing emulgel dressings showed an
      80% reduction in scar elevation compared with untreated controls. Topical
      formulations were nontoxic for cultured human keratinocytes and fibroblasts.
      Inflammation was significantly controlled in treated wounds, as shown by a
      reduced number of infiltrated CD3(+)  T cells (p < 0.001) and macrophages.
      SFN/ASA-treated wounds showed a significantly higher (p < 0.001) expression of
      matrix metalloproteinase-1, resulting in reduced collagen deposition and less
      scarring. Film-forming emulgel dressings that control the release of
      antifibrogenic and anti-inflammatory factors provide an excellent treatment
      option for postburn hypertrophic scar management.

PMID- 23126517
TI  - iMinerva: a mathematical model of distributional statistical learning.
AB  - Statistical learning refers to the ability to identify structure in the input
      based on its statistical properties. For many linguistic structures, the relevant
      statistical features are distributional: They are related to the frequency and
      variability of exemplars in the input. These distributional regularities have
      been suggested to play a role in many different aspects of language learning,
      including phonetic categories, using phonemic distinctions in word learning, and
      discovering non-adjacent relations. On the surface, these different aspects share
      few commonalities. Despite this, we demonstrate that the same computational
      framework can account for learning in all of these tasks. These results support
      two conclusions. The first is that much, and perhaps all, of distributional
      statistical learning can be explained by the same underlying set of processes.
      The second is that some aspects of language can be learned due to domain-general
      characteristics of memory.

PMID- 23126518
TI  - Fibrocalculous pancreatic diabetes in a young Ugandan patient, a rare form of
      secondary diabetes.
AB  - BACKGROUND: Fibrocalculous pancreatic diabetes is an infrequent type of secondary
      diabetes due to chronic tropical non alcoholic calcific pancreatitis. It has been
      widely described exclusively in developing tropical countries. A diagnosis is
      made basing on the presence of abdominal pain, presence of pancreatic
      calcifications, steatorrhoea, and diabetes mellitus. CASE PRESENTATION: We report
      a case of a 20 year old Ugandan female patient who presented with features of
      chronic tropical calcific pancreatitis complicated by diabetes mellitus,
      oedematous malnutrition and micronutrient deficiencies. CONCLUSION: This case
      report demonstrates that fibrocalculous pancreatic diabetes still exists in
      developing countries like Uganda. Clinicians in such settings should possess a
      high clinical suspicion of fibrocalculous pancreatic diabetes especially in
      presence of malnutrition. Challenges of management of such patients in resource
      limited settings are comprehensively discussed in the review of literature.

PMID- 23126519
TI  - Prevalence of migraine in patients with celiac disease and inflammatory bowel
      disease.
AB  - OBJECTIVE: To assess the prevalence of headache in clinic and support group
      patients with celiac disease and inflammatory bowel disease (IBD) compared with a
      sample of healthy controls. BACKGROUND: European studies have demonstrated
      increased prevalence of headache of patients with celiac disease compared with
      controls. METHODS: Subjects took a self-administered survey containing clinical,
      demographic, and dietary data, as well as questions about headache type and
      frequency. The ID-Migraine screening tool and the Headache Impact Test (HIT-6)
      were also used. RESULTS: Five hundred and two subjects who met exclusion criteria
      were analyzed - 188 with celiac disease, 111 with IBD, 25 with gluten sensitivity
      (GS), and 178 controls (C). Chronic headaches were reported by 30% of celiac
      disease, 56% of GS, 23% of IBD, and 14% of control subjects (P<.0001). On
      multivariate logistic regression, celiac disease (odds ratio [OR] 3.79, 95%
      confidence interval [CI] 1.78-8.10), GS (OR 9.53, 95%CI 3.24-28.09), and IBD (OR
      2.66, 95%CI 1.08-6.54) subjects all had significantly higher prevalence of
      migraine headaches compared with controls. Female sex (P=.01), depression, and
      anxiety (P=.0059) were independent predictors of migraine headaches, whereas age
      >65 was protective (P=.0345). Seventy-two percent of celiac disease subjects
      graded their migraine as severe in impact, compared with 30% of IBD, 60% of GS,
      and 50% of C subjects (P=.0919). There was no correlation between years on gluten
      free diet and migraine severity. CONCLUSIONS: Migraine was more prevalent in
      celiac disease and IBD subjects than in controls. Future studies should include
      screening migraine patients for celiac disease and assessing the effects of
      gluten-free diet on migraines in celiac disease.

PMID- 23126520
TI  - Nitrogen-doped colloidal graphene quantum dots and their size-dependent
      electrocatalytic activity for the oxygen reduction reaction.
AB  - Nitrogen doping has been a powerful way to modify the properties of carbon
      materials ranging from activated carbon to graphene. Here we report on a solution
      chemistry approach to nitrogen-doped colloidal graphene quantum dots with well
      defined structures. N-doping was demonstrated to significantly affect the
      properties of the quantum dots, including the emergence of size-dependent
      electrocatalytic activity for the oxygen reduction reaction.

PMID- 23126521
TI  - Prenatal antidepressant exposure and behavioral problems in early childhood--a
      cohort study.
AB  - OBJECTIVE: To estimate a potential association between in utero exposure to
      antidepressants and behavioral problems in childhood. METHOD: Information on
      exposures was obtained from the Danish National Birth Cohort. We studied the
      children of 127 mothers who had used antidepressants during pregnancy and
      compared these to 98 children of mothers with a prenatal depression with no use
      of antidepressants during pregnancy and 723 children of mothers with no prenatal
      depression and no use of antidepressant during pregnancy (unexposed). Behavioral
      problems were assessed at 4 or 5 years of age by the parent-reported Strengths
      and Difficulties Questionnaire (SDQ). RESULTS: Prenatal antidepressant exposure
      was not associated with abnormal SDQ scores compared with prenatal exposure to
      untreated prenatal depression or to no exposure. Untreated prenatal depression
      was associated with abnormal SDQ scores in the subscales of conduct [adjusted
      odds ratio (aOR) 2.3 (95% CI, 1.2-4.5)] and prosocial problems [aOR 3.0 (95% CI,
      1.2-7.8)] compared with unexposed children. Total SDQ score was higher in
      children of mothers with untreated prenatal depression. These associations
      attenuated after adjusting for postnatal maternal psychiatric disease.
      CONCLUSION: Prenatal antidepressant exposure was not associated with behavioral
      or emotional problems in early childhood.

PMID- 23126522
TI  - LC-DAD-MS-based metabolite profiling of three species of Justicia (Acanthaceae).
AB  - Olean-12-en-3beta-24 diol (A), auranamide (B), aurantiamide acetate (C),
      2alpha,3beta-dihydroxy-olean-12-en-28-oic acid (D) and quindoline (E) were
      isolated from the dichloromethane (CH2Cl2) extract of the stems of Justicia
      secunda (Acanthaceae). Liquid chromatography with ultraviolet and mass
      spectrometric detection was used to acquire more knowledge of the chemical
      composition of this extract and to monitor variations in profiles of both the
      isolated and the other non-identified compounds in Justicia refractifolia and
      Justicia graciliflora. The compound classes, phenolic and olefinic amides,
      feruloyltyramine amides, 2,5-diaryl-3,4-dimethyltetrahydrofuranoid lignans,
      peptide alkaloids, phenylalanine derivatives, conjugated ynones, indolquinoline
      alkaloids, triterpenes and pigments, were tentatively identified based on the LC
      DAD-APCI-MS analysis. The most frequently encountered compound among the species
      was auranamide while the distribution of quindoline was limited to J. secunda.
      Moreover, the acetylcholinesterase inhibitory activity of the isolated compounds
      was determined.

PMID- 23126523
TI  - Assessment of the interstitial fluid pressure of tumors by dynamic contrast
      enhanced magnetic resonance imaging with contrast agents of different molecular
      weights.
AB  - BACKGROUND: Cancer patients showing highly elevated interstitial fluid pressure
      (IFP) in the primary tumor may benefit from particularly aggressive treatment.
      There is some evidence that gadolinium diethylene-triamine penta-acetic acid (Gd
      DTPA)-based dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) may be
      a useful non-invasive method for providing information on the IFP of tumors. The
      purpose of this preclinical study was to investigate whether any association
      between DCE-MRI-derived parametric images and tumor IFP can be strengthened by
      using MR contrast agents with higher molecular weights than that of Gd-DTPA.
      MATERIAL AND METHODS: A-07 human melanoma xenografts were used as preclinical
      models of human cancer. Three contrast agents were compared: Gd-DTPA (0.55 kDa),
      P846 (3.5 kDa), and gadomelitol (6.5 kDa). A total of 46 tumors were subjected to
      DCE-MRI and subsequent measurement of IFP. Parametric images of K(trans) (the
      volume transfer constant of the contrast agent) and v(e) (the fractional
      distribution volume of the contrast agent) were produced by pharmacokinetic
      analysis of the DCE-MRI series. RESULTS: Significant inverse correlations were
      found between median K(trans) and IFP for Gd-DTPA (p = 0.0076; R(2) = 0.46; n =
      14) and P846 (p = 0.0042; R(2) = 0.45; n = 16), whereas there was no correlation
      between median K(trans) and IFP for gadomelitol (p > 0.05; n = 16). Significant
      correlation between median v(e) and IFP was not found for any of the contrast
      agents (p > 0.05 for Gd-DTPA, P846, and gadomelitol). CONCLUSION: K(trans)
      images, but not v(e) images, derived by pharmacokinetic analysis of DCE-MRI data
      for low-molecular-weight contrast agents may provide information on the IFP of
      tumors. Any association between K(trans) and IFP cannot be expected to be
      improved by using contrast agents with higher molecular weights than those of Gd
      DTPA and P846.

PMID- 23126524
TI  - Comparable cell survival between high dose rate flattening filter free and
      conventional dose rate irradiation.
AB  - PURPOSE: Investigation of clonogenic cell survival and cell proliferation
      following single dose and fractionated delivery of high dose rate flattening
      filter free (FFF) irradiation compared to conventional dose rates. MATERIAL AND
      METHODS: The human astrocytoma D384, glioma T98 and lung carcinoma SW1573 cell
      lines were irradiated using either a single dose (0-12 Gy) or a fractionated
      protocol of 5 daily fractions of 2 Gy (D384) or 3 Gy (SW1573). Cells were
      irradiated inside a phantom using fixed gantry beams of a linear accelerator. A
      sliding window technique created homogeneous dose distributions over the surface
      of the cell cultures. Irradiations using standard beams (6 MV, 600 MU/min.) and
      high dose rate FFF beams (10 MV, 2400 MU/min.) were compared. Cell survival was
      determined by clonogenic assay. In the fractionated irradiation set-up, the
      number of clonogenic cells was estimated by including tumor cell proliferation
      during the overall treatment time in the analysis. RESULTS: All cell lines showed
      equal cell survival following irradiation using either the FFF beams or
      conventional flattened (FF) beams. This was observed after single dose exposure
      (0-12 Gy) as well as after fractionated irradiation (p = 0.08 for D384 and 0.20
      for SW1373 cell lines). CONCLUSION: FFF irradiation with a dose rate of 2400
      MU/min and four times higher dose per pulse compared to irradiation with FF beams
      did not change cell survival for three human cancer cell lines up to a fraction
      dose of 12 Gy compared to irradiation using FF beams.

PMID- 23126525
TI  - The modulatory effect of melatonin on genotoxicity of irinotecan in healthy human
      lymphocytes and cancer cells.
AB  - Drug-target interactions can be modified by adding modulatory agents to increase
      treatment efficacy and clinical outcome. Combination chemotherapy has become
      increasingly important because drugs acting synergistically can achieve
      therapeutic effects at substantially lower doses and with a limited spectrum of
      side effects. Irinotecan, known as one of the camptothecin analogs, has shown a
      broad spectrum of antitumor activity against various malignancies. In this study,
      we evaluated the effect of melatonin on the genotoxic activity of irinotecan in
      healthy human lymphocytes and a lung cancer cell line (A549) and a colorectal
      adenocarcinoma cell line (HT29) in vitro. Irinotecan, as a single agent, was
      shown to induce DNA damage in all types of analyzed cells. The combination of
      melatonin at concentrations of 50 MUM with increasing doses of irinotecan (7.5,
      15, 30, and 60 MUM) resulted in an increase in the amount of DNA damage in A549
      and HT29 cancer cells, but was not effective in inducing DNA damage in healthy
      human lymphocytes. Analysis of the efficacy of DNA repair, performed after 60 and
      120 minutes of postincubation, showed the gradual decrease of DNA percentage in
      comet tails during repair postincubation in all experimental samples. Our results
      indicate that melatonin can modulate the genotoxic activity of irinotecan and DNA
      repair efficacy in human cancer cells in vitro. These findings may be supportive
      for the optimization of therapeutic efficacy in irinotecan treatment.

PMID- 23126526
TI  - Towards scalable production of a collagen-like protein from Streptococcus
      pyogenes for biomedical applications.
AB  - BACKGROUND: Collagen has proved valuable as biomedical materials for a range of
      clinical applications, particularly in wound healing. It is normally produced
      from animal sources, such as from bovines, but concerns have emerged over
      transmission of diseases. Recombinant collagens would be preferable, but are
      difficult to produce. Recently, studies have shown that 'collagens' from
      bacteria, including Streptococcus pyogenes, can be produced in the laboratory as
      recombinant products, and that these are biocompatible. In the present study we
      have established that examples of bacterial collagens can be produced in a
      bioreactor with high yields providing proof of manufacture of this important
      group of proteins. RESULTS: Production trials in shake flask cultures gave low
      yields of recombinant product, < 1 g/L. Increased yields, of around 1 g/L, were
      obtained when the shake flask process was transferred to a stirred tank
      bioreactor, and the yield was further enhanced to around 10 g/L by implementation
      of a high cell density fed-batch process and the use of suitably formulated fully
      defined media. Similar yields were obtained with 2 different constructs, one
      containing an introduced heparin binding domain. The best yields, of up to 19 g/L
      were obtained using this high cell density strategy, with an extended 24 h
      production time. CONCLUSIONS: These data have shown that recombinant bacterial
      collagen from S. pyogenes, can be produced in sufficient yield by a scalable
      microbial production process to give commercially acceptable yields for broad use
      in biomedical applications.

PMID- 23126527
TI  - Illness perceptions and treatment perceptions of patients with chronic kidney
      disease: different phases, different perceptions?
AB  - OBJECTIVES: To examine the variability of illness and treatment perceptions -
      that have been found to be associated with chronic kidney disease (CKD) patients'
      outcomes (e.g., quality of life) - across the CKD trajectory, by investigating
      whether there are differences in perceptions in patients: (1) on varying
      treatments (pre-dialysis, haemodialysis, peritoneal dialysis), (2) with varying
      lengths of time on (dialysis) treatment, and (3) over time on dialysis, with an 8
      month interval. DESIGN AND METHODS: Mixed cross-sectional and longitudinal
      design, using self-report questionnaires on illness and treatment perceptions;
      the study sample consisted of 105 pre-dialysis and 161 dialysis patients; of the
      161 dialysis patients, 87 patients filled in the questionnaires again after an 8
      month interval. Data were examined using multilevel (multivariate) repeated
      measurements regression analyses, controlled for background characteristics and
      repeated measures. RESULTS: Patients on haemodialysis and peritoneal dialysis
      believed more strongly that their treatment controls their illness (p < .05, p <
      .01, respectively) and perceived more illness consequences (p < .001, p < .05,
      respectively) than pre-dialysis patients. Haemodialysis patients perceived more
      treatment consequences than pre-dialysis (p < .001) and peritoneal dialysis
      patients (p < .01). The perception of illness understanding fluctuated between
      patients with varying lengths of time on dialysis (p < .05). Perceived treatment
      consequences were more negative in patients who were on dialysis for longer
      lengths of time (p < .01). Lastly, perceptions of illness and treatment varied
      within dialysis patients over an 8-month interval, with treatment control and
      personal control showing the lowest correlations. CONCLUSIONS: Findings suggest
      that illness and treatment perceptions vary across the CKD trajectory. This
      indicates that perceptions are amenable to influences and that interventions
      might potentially be helpful in influencing them in order to improve outcomes.
      STATEMENT OF CONTRIBUTION: What is already known on this subject? Dialysis
      patients' perceptions of illness understanding and illness symptoms vary over the
      first year on dialysis. Established haemodialysis patients' perceptions of
      illness understanding, emotional response and treatment control vary over a 2
      year period. Certain illness perceptions as well as treatment perceptions vary as
      a function of treatment type in patients with CKD stage 5 (dialysis patients,
      patients with a kidney transplant). What does this study add? Patients'
      perceptions of illness understanding and treatment consequences vary between
      patients as a function of length of time on (haemo-, peritoneal-) dialysis,
      taking into account a wide range of time (0-10 years). Illness perceptions and
      treatment perceptions of patients on haemodialysis and peritoneal dialysis vary
      within patients over an 8-month interval, with perceptions of treatment control
      and personal control showing the highest variations. Perceptions of illness
      consequences, treatment consequences and treatment control vary as a function of
      type of treatment, taking into account pre-dialysis treatment (CKD stage 4) and
      dialysis (haemodialysis, peritoneal dialysis) treatment (CKD stage 5).

PMID- 23126528
TI  - The utility of comparative models and the local model quality for protein crystal
      structure determination by Molecular Replacement.
AB  - BACKGROUND: Computational models of protein structures were proved to be useful
      as search models in Molecular Replacement (MR), a common method to solve the
      phase problem faced by macromolecular crystallography. The success of MR depends
      on the accuracy of a search model. Unfortunately, this parameter remains unknown
      until the final structure of the target protein is determined. During the last
      few years, several Model Quality Assessment Programs (MQAPs) that predict the
      local accuracy of theoretical models have been developed. In this article, we
      analyze whether the application of MQAPs improves the utility of theoretical
      models in MR. RESULTS: For our dataset of 615 search models, the real local
      accuracy of a model increases the MR success ratio by 101% compared to
      corresponding polyalanine templates. On the contrary, when local model quality is
      not utilized in MR, the computational models solved only 4.5% more MR searches
      than polyalanine templates. For the same dataset of the 615 models, a workflow
      combining MR with predicted local accuracy of a model found 45% more correct
      solution than polyalanine templates. To predict such accuracy MetaMQAPclust, a
      "clustering MQAP" was used. CONCLUSIONS: Using comparative models only marginally
      increases the MR success ratio in comparison to polyalanine structures of
      templates. However, the situation changes dramatically once comparative models
      are used together with their predicted local accuracy. A new functionality was
      added to the GeneSilico Fold Prediction Metaserver in order to build models that
      are more useful for MR searches. Additionally, we have developed a simple method,
      AmIgoMR (Am I good for MR?), to predict if an MR search with a template-based
      model for a given template is likely to find the correct solution.

PMID- 23126529
TI  - Evaluation and validation of two microbiological tests for screening antibiotic
      residues in honey according to the European guideline for the validation of
      screening methods.
AB  - Two microbiological kits based on Bacillus stearothermophilus (Eclipse 50(r) and
      Premi(r)Test) have been evaluated and validated according to the European
      guideline for the validation of screening methods (January 2010) and in relation
      to the concentrations recommended by the EU-RL in 2007. Both tests are robust, a
      fast method and easy to implement. Both tests are applicable to a very large
      variety of honeys from different floral and geographical origins (rosemary,
      lavender, scrub, heath, alder, forest, lemon, acacia, chestnut, raspberry,
      mountain and flowers) as well as honey of different colours (from blank honey to
      brown honey, including yellow and orange honey). A satisfactory false-positive
      rate of 5% was obtained for the Eclipse 50(r) test. The observed detection
      capabilities CCbeta of the Eclipse 50(r) kit were: chlortetracycline (>75 ug kg(
      1)), oxytetracycline (<=200 ug kg(-1)), tetracycline (>100 ug kg(-1)),
      cloxacillin (<=40 ug kg(-1)), tylosin (<=200 ug kg(-1)), desmycosin (>400 ug kg(
      1)), sulfadiazine (<=300 ug kg(-1)), sulfadimethoxine (<=250 ug kg(-1)),
      sulfamerazine (>300 ug kg(-1)), sulfamethazine (>1000 ug kg(-1)), sulfamethizole
      (>75 ug kg(-1)), sulfamethoxazole (<=25 ug kg(-1)), sulfanilamide (>>1000 ug kg(
      1)), sulfaquinoxaline (>75 ug kg(-1)), sulfathiazole (<=250 ug kg(-1)) and
      lincomycin (>1500 ug kg(-1)). These levels were all higher than the recommended
      concentrations where they exist. Due to its lack of sensitivity, it cannot be
      recommended for reliable routine use. The observed CCbeta of the Premi(r)Test kit
      were: chlortetracycline (10 ug kg(-1)), oxytetracycline (>10 ug kg(-1)),
      tetracycline (<=10 ug kg(-1)), cloxacillin (<=5 ug kg(-1)), tylosin (<=10 ug kg(
      1)), desmycosin (<=15 ug kg(-1)), sulfadiazine (<=25 ug kg(-1)), sulfadimethoxine
      (<=25 ug kg(-1)), sulfamerazine (<=25 ug kg(-1)), sulfamethazine (<=25 ug kg(
      1)), sulfamethizole (<=25 ug kg(-1)), sulfamethoxazole (<=10 ug kg(-1)),
      sulfanilamide (<=25 ug kg(-1)), sulfaquinoxaline (<=10 ug kg(-1)), sulfathiazole
      (25 ug kg(-1)) and lincomycin (<=25 ug kg(-1)). The Premi(r)Test kit could be
      recommended for reliable use in routine control due to its low detection
      capabilities (except for aminoglycosides), but the disadvantage is a high false
      positive rate of 14%.

PMID- 23126530
TI  - Doppler indices of intrarenal arterial stiffness are useful in monitoring
      scleroderma renal crisis.

PMID- 23126531
TI  - Alcohol facilitates HCV RNA replication via up-regulation of miR-122 expression
      and inhibition of cyclin G1 in human hepatoma cells.
AB  - BACKGROUND: Clinical studies demonstrate synergistic liver damage by alcohol and
      hepatitis C virus (HCV); however, the mechanisms by which alcohol promotes HCV
      infection remain obscure. The liver-specific microRNA-122 (miR-122) regulates HCV
      replication and expression of host genes, including Cyclin G1. Here, we
      hypothesized that alcohol regulates miR-122 expression and thereby modulates HCV
      RNA replication. METHODS: The J6/JFH/Huh-7.5 model of HCV infection was used in
      this study. Real-time quantitative polymerase chain reaction, Western blotting,
      electrophoretic mobility shift assay, and confocal microscopy were used for
      experimental analysis. RESULTS: We found that acute alcohol exposure (25 mM)
      significantly increased intracellular HCV RNA as well as miR-122 levels in Huh
      7.5 and Huh-7.5/CYP2E1 expressing cells in the presence and absence of J6/JFH-HCV
      infection. Expression of the miR-122 target, Cyclin G1, was inhibited by alcohol
      both in J6/JFH-infected and uninfected Huh-7.5 cells. The use of a miR-122
      inhibitor increased Cyclin G1 expression and prevented the alcohol-induced
      increase in HCV RNA and protein levels, suggesting a mechanistic role for alcohol
      induced miR122 in HCV replication. We discovered that siRNA-mediated silencing of
      Cyclin G1 significantly increased intracellular HCV RNA levels compared with
      controls, suggesting a mechanistic role for Cyclin G1 in HCV replication. Alcohol
      induced increase in miR-122 was associated with increased nuclear translocation
      and DNA binding of the nuclear regulatory factor-kappaB and could be prevented by
      NF-kappaB inhibition. CONCLUSIONS: Our novel data indicate a miR-122-mediated
      mechanism for alcohol increasing HCV RNA replication. We show for the first time
      that Cyclin G1, a miR-122 target gene, has regulatory effects on HCV replication
      and that alcohol increases HCV replication by regulating miR-122 and Cyclin G1.

PMID- 23126532
TI  - Functional response to cholinesterase inhibitor therapy in a naturalistic
      Alzheimer's disease cohort.
AB  - BACKGROUND: Activities of daily living (ADL) are an essential part of the
      diagnostic criteria for Alzheimer's disease (AD). A decline in ADL affects
      independent living and has a strong negative impact on caregiver burden.
      Functional response to cholinesterase inhibitor (ChEI) treatment and factors that
      might influence this response in naturalistic AD patients need investigating. The
      aim of this study was to identify the socio-demographic and clinical factors that
      affect the functional response after 6 months of ChEI therapy. METHODS: This
      prospective, non-randomised, multicentre study in a routine clinical setting
      included 784 AD patients treated with donepezil, rivastigmine or galantamine. At
      baseline and after 6 months of treatment, patients were assessed using several
      rating scales, including the Instrumental Activities of Daily Living (IADL)
      scale, Physical Self-Maintenance Scale (PSMS) and Mini-Mental State Examination
      (MMSE). Demographic and clinical characteristics were investigated at baseline.
      The functional response and the relationships of potential predictors were
      analysed using general linear models. RESULTS: After 6 months of ChEI treatment,
      49% and 74% of patients showed improvement/no change in IADL and in PSMS score,
      respectively. The improved/unchanged patients exhibited better cognitive status
      at baseline; regarding improved/unchanged PSMS, patients were younger and used
      fewer anti-depressants. A more positive functional response to ChEI was observed
      in younger individuals or among those having the interaction effect of better
      preserved cognition and lower ADL ability. Patients with fewer concomitant
      medications or those using NSAIDs/acetylsalicylic acid showed a better PSMS
      response. CONCLUSIONS: Critical characteristics that may influence the functional
      response to ChEI in AD were identified. Some predictors differed from those
      previously shown to affect cognitive response, e.g., lower cognitive ability and
      older age predicted better cognitive but worse functional response.

PMID- 23126533
TI  - Parametric analysis of a novel cryogenic CO2 capture system based on Stirling
      coolers.
AB  - CO(2) capture and storage (CCS) is an important alternative to control greenhouse
      gas (GHG) effects. In previous work, a novel desublimation CO(2) capture process
      has been exploited making use of three free piston Stirling coolers (namely, SC
      1, SC-2, and SC-3, respectively). Based on the developed system, moisture and
      CO(2) in the flue gas can condense and desublimate in the prefreezing and main
      freezing towers, respectively. Meanwhile, the storage column is chilled by SC-3
      to preserve the frosted CO(2), and permanent gas (such as N(2)) passes through
      the system without phase change. The whole process can be implemented at
      atmospheric pressure and reduce the energy penalty (e.g., solvent regeneration
      and pressure drop) in other technologies. In this work, the influence of process
      parameters has been investigated in detail. The optimal conditions for the system
      are as follows: idle operating time is 240 min, flow rate is 5 L/min, vacuum
      degree of the interlayer is 2.2 * 10(3) Pa, and temperatures of SC-1, -2, and -3
      are -30, -120, and -120  degrees C, respectively. Under these conditions, the
      energy consumption of the system is around 0.5 MJ(electrical)/kg CO(2) with above
      90% CO(2) recovery.

PMID- 23126534
TI  - Complementary and alternative therapies for back pain II.
AB  - BACKGROUND: Back and neck pain are important health problems with serious
      societal and economic implications. Conventional treatments have been shown to
      have limited benefit in improving patient outcomes. Complementary and Alternative
      Medicine (CAM) therapies offer additional options in the management of low back
      and neck pain. Many trials evaluating CAM therapies have poor quality and
      inconsistent results. OBJECTIVES: To systematically review the efficacy,
      effectiveness, cost-effectiveness, and harms of acupuncture, spinal manipulation,
      mobilization, and massage techniques in management of back, neck, and/or thoracic
      pain. DATA SOURCES: MEDLINE, Cochrane Central, Cochrane Database of Systematic
      Reviews, CINAHL, and EMBASE were searched up to 2010; unpublished literature and
      reference lists of relevant articles were also searched. study selection: All
      records were screened by two independent reviewers. Primary reports of
      comparative efficacy, effectiveness, harms, and/or economic evaluations from
      randomized controlled trials (RCTs) of the CAM therapies in adults (age >= 18
      years) with back, neck, or thoracic pain were eligible. Non-randomized controlled
      trials and observational studies (case-control, cohort, cross-sectional)
      comparing harms were also included. Reviews, case reports, editorials,
      commentaries or letters were excluded. DATA EXTRACTION: Two independent reviewers
      using a predefined form extracted data on study, participants, treatments, and
      outcome characteristics. RESULTS: 265 RCTs and 5 non-RCTs were included.
      Acupuncture for chronic nonspecific low back pain was associated with
      significantly lower pain intensity than placebo but only immediately post
      treatment (VAS: -0.59, 95 percent CI: -0.93, -0.25). However, acupuncture was not
      different from placebo in post-treatment disability, pain medication intake, or
      global improvement in chronic nonspecific low back pain. Acupuncture did not
      differ from sham-acupuncture in reducing chronic non-specific neck pain
      immediately after treatment (VAS: 0.24, 95 percent CI: -1.20, 0.73). Acupuncture
      was superior to no treatment in improving pain intensity (VAS: -1.19, 95 percent
      CI: 95 percent CI: -2.17, -0.21), disability (PDI), functioning (HFAQ), well
      being (SF-36), and range of mobility (extension, flexion), immediately after the
      treatment. In general, trials that applied sham-acupuncture tended to produce
      negative results (i.e., statistically non-significant) compared to trials that
      applied other types of placebo (e.g., TENS, medication, laser). Results regarding
      comparisons with other active treatments (pain medication, mobilization, laser
      therapy) were less consistent Acupuncture was more cost-effective compared to
      usual care or no treatment for patients with chronic back pain. For both low back
      and neck pain, manipulation was significantly better than placebo or no treatment
      in reducing pain immediately or short-term after the end of treatment.
      Manipulation was also better than acupuncture in improving pain and function in
      chronic nonspecific low back pain. Results from studies comparing manipulation to
      massage, medication, or physiotherapy were inconsistent, either in favor of
      manipulation or indicating no significant difference between the two treatments.
      Findings of studies regarding costs of manipulation relative to other therapies
      were inconsistent. Mobilization was superior to no treatment but not different
      from placebo in reducing low back pain or spinal flexibility after the treatment.
      Mobilization was better than physiotherapy in reducing low back pain (VAS: -0.50,
      95 percent CI: -0.70, -0.30) and disability (Oswestry: -4.93, 95 percent CI: 
      5.91, -3.96). In subjects with acute or subacute neck pain, mobilization compared
      to placebo significantly reduced neck pain. Mobilization and placebo did not
      differ in subjects with chronic neck pain. Massage was superior to placebo or no
      treatment in reducing pain and disability only amongst subjects with acute/sub
      acute low back pain. Massage was also significantly better than physical therapy
      in improving back pain (VAS: -2.11, 95 percent CI: -3.15, -1.07) or disability.
      For subjects with neck pain, massage was better than no treatment, placebo, or
      exercise in improving pain or disability, but not neck flexibility. Some evidence
      indicated higher costs for massage use compared to general practitioner care for
      low back pain. Reporting of harms in RCTs was poor and inconsistent. Subjects
      receiving CAM therapies reported soreness or bleeding on the site of application
      after acupuncture and worsening of pain after manipulation or massage. In two
      case-control studies cervical manipulation was shown to be significantly
      associated with vertebral artery dissection or vertebrobasilar vascular accident.
      CONCLUSIONS: Evidence was of poor to moderate grade and most of it pertained to
      chronic nonspecific pain, making it difficult to draw more definitive conclusions
      regarding benefits and harms of CAM therapies in subjects with acute/subacute,
      mixed, or unknown duration of pain. The benefit of CAM treatments was mostly
      evident immediately or shortly after the end of the treatment and then faded with
      time. Very few studies reported long-term outcomes. There was insufficient data
      to explore subgroup effects. The trial results were inconsistent due probably to
      methodological and clinical diversity, thereby limiting the extent of
      quantitative synthesis and complicating interpretation of trial results. Strong
      efforts are warranted to improve the conduct methodology and reporting quality of
      primary studies of CAM therapies. Future well powered head to head comparisons of
      CAM treatments and trials comparing CAM to widely used active treatments that
      report on all clinically relevant outcomes are needed to draw better conclusions.

PMID- 23126535
TI  - Botulinum toxin type A injection for neurogenic detrusor overactivity: clinical
      outcome in Japanese patients.
AB  - OBJECTIVES: To report our experience with intravesical injection of botulinum
      toxin type A into the detrusor muscle of patients with neurogenic detrusor
      overactivity secondary to suprasacral spinal cord lesions or multiple sclerosis.
      METHODS: Between January 2003 and March 2011, 11 patients (aged 23-75 years) were
      treated with 40 injections of botulinum toxin type A 300 U. The patients were
      followed up for 4, 8 and 12 weeks after treatment. The King's Health
      Questionnaire was administered and cystometric studies were carried out at
      baseline and 8 weeks after treatment. RESULTS: A total of six women and five men
      were treated. Analysis of the King's Health Questionnaire showed a significant
      improvement in eight of the nine domain scores at 8 weeks from baseline. On
      cystometric studies, the mean maximum cystometric capacity increased
      significantly in all patients at 8 weeks from baseline (P < 0.001). Bladder
      compliance also increased significantly (P < 0.001). The number of urinary
      incontinence episodes per day improved significantly from baseline after
      injection (4 weeks, P < 0.001; 8 weeks, P < 0.001; 12 weeks, P < 0.001). Lack of
      efficacy appeared 7.15 +/- 3.4 months after treatment. CONCLUSIONS: Injection of
      botulinum toxin type A into the detrusor muscle of patients with neurogenic
      detrusor overactivity secondary to suprasacral spinal cord lesions or multiple
      sclerosis consistently improves bladder control and quality of life.

PMID- 23126536
TI  - Generation of potent cytotoxic T lymphocytes against castration-resistant
      prostate cancer cells by dendritic cells loaded with dying allogeneic prostate
      cancer cells.
AB  - To induce a potent cytotoxic T lymphocyte (CTL) response in dendritic cell (DC)
      based immunotherapy against prostate cancer, various tumour antigens should be
      loaded onto DCs. The aim of this study was to establish a method of immunotherapy
      for castration-resistant prostate cancer (CRPC) using prostate cancer-specific
      CTLs generated in vitro by DCs. Monocyte-derived DCs from patients with CRPC were
      induced to mature using a standard cytokine cocktail (in IL-1beta, TNF-alpha, IL
      6 and PGE(2) : standard DCs, sDCs) or using an alpha-type 1-polarized DC
      (alphaDC1) cocktail (in IL-1beta, TNF-alpha, IFN-alpha, IFN-gamma and
      polyinosinic:polycytidylic acid) and loaded with the UVB-irradiated CRPC cell
      line PC-3. Antigen-loaded DCs were evaluated by morphological and functional
      assays. The alphaDC1s significantly increased the expression of several molecules
      related to DC maturation, regardless of whether the alphaDC1s were loaded with
      tumour antigens or not, compared to sDCs. The alphaDC1s showed a higher
      production of interleukin-12 both during maturation and after subsequent
      stimulation with CD40L, which was not significantly affected by loading with
      tumour antigens, as compared to standard DCs (sDCs). Prostate cancer-specific
      CTLs against autologous CRPC cells were successfully induced by alphaDC1s loaded
      with dying PC-3 cells. Autologous alphaDC1s loaded with an allogeneic CRPC cell
      line can generate greater CRPC-specific CTL responses as compared to sDCs and may
      provide a novel source of DC-based vaccines that can be used for the development
      of immunotherapy in patients with CRPC.

PMID- 23126537
TI  - Silicon isotope ratios affected by sodium-induced broadband interference in high
      resolution multicollector-ICPMS.
AB  - The measurement of isotope ratios of silicon highly enriched in (28)Si ("Si28",
      x((28)Si) > 99.99%) is influenced by a significant interference (20%) on the
      (30)Si(+) signal when using a cup configuration of C ((29)Si(+)) and H3
      ((30)Si(+)) on a Neptune MC-ICPMS. This interference was observed in silicon
      solutions with aqueous NaOH (w(NaOH) > 0.001 g/g) and in highly concentrated
      aqueous NaOH blank solutions (e.g., w(NaOH) = 0.25 g/g) but never in KOH
      solutions. By redirecting the ions, the interference was detected with all other
      Faraday cups except the center cup. The interference can be explained by ion
      scattering induced by the presence of large amounts of sodium. Due to its
      shielded location, these stray ions were not detected in the center cup. This
      effect explains an anomalous increase of the abundance of the (30)Si(+) signal in
      (30)Si/(29)Si isotope ratio measurements made using aqueous NaOH blank solutions
      with w(NaOH) >= 0.001 g/g. For silicon isotopic measurements, it is recommended
      to use alkaline solutions for sample dissolution and dilution that do not contain
      sodium. The effects of this interference are extremely important for the
      experimental determination of the Avogadro constant N(A) using the "silicon
      sphere approach". It can also have a significant effect on Si isotope analyses in
      matrices with a naturally high concentration of sodium (e.g., seawater).

PMID- 23126539
TI  - Unifying the aspects of the Big Five, the interpersonal circumplex, and trait
      affiliation.
AB  - OBJECTIVE: Two dimensions of the Big Five, Extraversion and Agreeableness, are
      strongly related to interpersonal behavior. Factor analysis has indicated that
      each of the Big Five contains two separable but related aspects. The present
      study examined the manner in which the aspects of Extraversion (Assertiveness and
      Enthusiasm) and Agreeableness (Compassion and Politeness) relate to interpersonal
      behavior and trait affiliation, with the hypothesis that these four aspects have
      a structure corresponding to the octants of the interpersonal circumplex. A
      second hypothesis was that measures of trait affiliation would fall between
      Enthusiasm and Compassion in the IPC. METHOD: These hypotheses were tested in
      three demographically different samples (N = 469; 294; 409) using both behavioral
      frequency and trait measures of the interpersonal circumplex, in conjunction with
      the Big Five Aspect Scales (BFAS) and measures of trait affiliation. RESULTS:
      Both hypotheses were strongly supported. CONCLUSIONS: These findings provide a
      more thorough and precise mapping of the interpersonal traits within the Big Five
      and support the integration of the Big Five with models of interpersonal behavior
      and trait affiliation.

PMID- 23126540
TI  - A stereoselective cyclization strategy for the preparation of gamma-lactams and
      their use in the synthesis of alpha-methyl-beta-proline.
AB  - A straightforward stereoselective and enantiodivergent cyclization strategy for
      the construction of gamma-lactams is described. The cyclization strategy makes
      use of chiral malonic esters prepared from enantiomerically enriched monoesters
      of disubstituted malonic acid. The cyclization occurs with the selective
      displacement of a substituted benzyl alcohol as the leaving group. A Hammett
      study illustrates that the cyclization is under electronic control. The resulting
      gamma-lactam can be readily converted into a novel proline analogue.

PMID- 23126541
TI  - Embryonic stem cell-derived M2-like macrophages delay cutaneous wound healing.
AB  - In adults, repair of deeply injured skin wounds results in the formation of scar
      tissue, whereas in embryos wounds heal almost scar-free. Macrophages are
      important mediators of wound healing and secrete cytokines and tissue remodeling
      enzymes. In contrast to host defense mediated by inflammatory M1 macrophages,
      wound healing and tissue repair involve regulatory M2/M2-like macrophages.
      Embryonic/fetal macrophages are M2-like, and this may promote scar-free wound
      healing. In the present study, we asked whether atopical application of ex vivo
      generated, embryonic stem cell-derived macrophages (ESDM) improve wound healing
      in mice. ESDM were tested side by side with bone marrow-derived macrophages
      (BMDM). Compared to BMDM, ESDM resembled a less inflammatory and more M2-like
      macrophage subtype as indicated by their reduced responsiveness to
      lipopolysaccharide, reduced expression of Toll-like receptors, and reduced
      bacterial phagocytosis. Despite this anti-inflammatory phenotype in cell culture,
      ESDM prolonged the healing of deep skin wounds even more than BMDM. Healed wounds
      had more scar formation compared to wounds receiving BMDM or cell-free treatment.
      Our data indicate that atopical application of ex vivo generated macrophages is
      not a suitable cell therapy of dermal wounds.

PMID- 23126542
TI  - Neural computation and the computational theory of cognition.
AB  - We begin by distinguishing computationalism from a number of other theses that
      are sometimes conflated with it. We also distinguish between several important
      kinds of computation: computation in a generic sense, digital computation, and
      analog computation. Then, we defend a weak version of computationalism-neural
      processes are computations in the generic sense. After that, we reject on
      empirical grounds the common assimilation of neural computation to either analog
      or digital computation, concluding that neural computation is sui generis. Analog
      computation requires continuous signals; digital computation requires strings of
      digits. But current neuroscientific evidence indicates that typical neural
      signals, such as spike trains, are graded like continuous signals but are
      constituted by discrete functional elements (spikes); thus, typical neural
      signals are neither continuous signals nor strings of digits. It follows that
      neural computation is sui generis. Finally, we highlight three important
      consequences of a proper understanding of neural computation for the theory of
      cognition. First, understanding neural computation requires a specially designed
      mathematical theory (or theories) rather than the mathematical theories of analog
      or digital computation. Second, several popular views about neural computation
      turn out to be incorrect. Third, computational theories of cognition that rely on
      non-neural notions of computation ought to be replaced or reinterpreted in terms
      of neural computation.

PMID- 23126543
TI  - An online survey of exercise-related headaches among cyclists.
AB  - BACKGROUND: Primary exertional headache (PEH) is a long-known phenomenon.
      Divergent prevalences of between 0.2 and 12.3% are reported among the general
      population. The aim of this study was to establish the prevalence among an
      athletic population. METHOD: A link to an online questionnaire was sent to all
      participants of a tough cycling event held in The Netherlands. RESULTS: Four
      thousand participants filled out the questionnaire. One thousand eight hundred
      and ten (45%) stated that they had suffered, at least once in their lives, from
      exercise-related headaches (EHs). Thirty-seven percent (668) of them had those
      headaches at least once a month and 10% (174) experienced a weekly occurrence.
      The rate of female cyclists with a history of EHs was 54%. With an increasing
      age, a decline of EHs was found. Five hundred eighty-one (37%) of the
      participants used medication for EHs. CONCLUSIONS: An estimation of the
      prevalence of PEHs among the studied population by comparison to the
      International Headache Society criteria resulted in a rate of 26%. The lower
      prevalence among older cyclists could be caused by avoidance of (high-intensity)
      exercise due to the burden that EH brings along. PEH appears to be quite common
      among an athletic population and merits further investigation.

PMID- 23126544
TI  - A comparison of internal model validation methods for multifactor dimensionality
      reduction in the case of genetic heterogeneity.
AB  - BACKGROUND: Determining the genes responsible for certain human traits can be
      challenging when the underlying genetic model takes a complicated form such as
      heterogeneity (in which different genetic models can result in the same trait) or
      epistasis (in which genes interact with other genes and the environment).
      Multifactor Dimensionality Reduction (MDR) is a widely used method that
      effectively detects epistasis; however, it does not perform well in the presence
      of heterogeneity partly due to its reliance on cross-validation for internal
      model validation. Cross-validation allows for only one "best" model and is
      therefore inadequate when more than one model could cause the same trait. We
      hypothesize that another internal model validation method known as a three-way
      split will be better at detecting heterogeneity models. RESULTS: In this study,
      we test this hypothesis by performing a simulation study to compare the
      performance of MDR to detect models of heterogeneity with the two different
      internal model validation techniques. We simulated a range of disease models with
      both main effects and gene-gene interactions with a range of effect sizes. We
      assessed the performance of each method using a range of definitions of power.
      CONCLUSIONS: Overall, the power of MDR to detect heterogeneity models was
      relatively poor, especially under more conservative (strict) definitions of
      power. While the overall power was low, our results show that the cross
      validation approach greatly outperformed the three-way split approach in
      detecting heterogeneity. This would motivate using cross-validation with MDR in
      studies where heterogeneity might be present. These results also emphasize the
      challenge of detecting heterogeneity models and the need for further methods
      development.

PMID- 23126545
TI  - High Curie temperature Bi(1.85)Mn(0.15)Te3 nanoplates.
AB  - Bi(1.85)Mn(0.15)Te(3) hexagonal nanoplates with a width of ~200 nm and a
      thickness of ~20 nm were synthesized using a solvothermal method. According to
      the structural characterization and compositional analysis, the Mn(2+) and Mn(3+)
      ions were found to substitute Bi(3+) ions in the lattice. High-level Mn doping
      induces significant lattice distortion and decreases the crystal lattice by 1.07%
      in the a axis and 3.18% in the c axis. A high ferromagnetic state with a Curie
      temperature of ~45 K is observed in these nanoplates due to Mn(2+) and Mn(3+) ion
      doping, which is a significant progress in the field of electronics and
      spintronics.

PMID- 23126546
TI  - Inhaled nitric oxide in preterm infants.
AB  - OBJECTIVES: To systematically review the evidence on the use of inhaled nitric
      oxide (iNO) in preterm infants born at or before 34 weeks gestation age who
      receive respiratory support. DATA SOURCES: We searched MEDLINE, EMBASE, the
      Cochrane Central Register of Controlled Studies (CENTRAL) and PsycInfo in June
      2010. We also searched the proceedings of the 2009 and 2010 Pediatric Academic
      Societies Meeting and ClinicalTrials.gov. We identified additional studies from
      reference lists of eligible articles and relevant reviews, as well as from
      technical experts. REVIEW METHODS: Questions were developed in collaboration with
      technical experts, including the chair of the upcoming National Institutes of
      Health Office of Medical Applications of Research Consensus Development
      Conference. We limited our review to randomized controlled trials (RCTs) for the
      question of survival or occurrence of bronchopulmonary dysplasia (BPD) and for
      the question on short-term risks. All study designs were considered for long-term
      pulmonary or neurodevelopmental outcomes, and for questions about whether
      outcomes varied by subpopulation or by intervention characteristics. Two
      investigators independently screened search results, and abstracted data from
      eligible articles. RESULTS: We identified a total of 14 RCTs, reported in 23
      articles, and eight observational studies. Mortality rates in the NICU did not
      differ for infants treated with iNO versus those not treated with iNO (RR 0.97
      (95% CI 0.82, 1.15)). BPD at 36 weeks for iNO and control groups also did not
      differ (RR 0.93 (0.86, 1.003) for survivors). A small difference was found
      between iNO and control infants in the composite outcome of death or BPD (RR 0.93
      (0.87, 0.99)). There was inconsistent evidence about the risk of brain injury
      from individual RCTs, but meta-analyses showed no difference between iNO and
      control groups. We found no evidence of differences in other short term risks.
      There was no evidence to suggest a difference in the incidence of cerebral palsy
      (RR 1.36 (0.88, 2.10)), neurodevelopmental impairment (RR 0.91 (0.77, 1.12)), or
      cognitive impairment (RR 0.72 (0.35, 1.45)). Evidence was limited on whether the
      effect of iNO varies by subpopulation or by characteristics of the therapy
      (timing, dose and duration, mode of delivery, or concurrent therapies).
      CONCLUSIONS: There was a seven percent reduction in the risk of the composite
      outcome of death or BPD at 36 weeks PMA for infants treated with iNO compared to
      controls, but no reduction in death or BPD alone. Further studies are needed to
      explore particular subgroups of infants and to assess long term outcomes
      including function in childhood. There is currently no evidence to support the
      use of iNO in preterm infants with respiratory failure outside the context of
      rigorously conducted randomized clinical trials.

PMID- 23126547
TI  - Rapid expansion of T cells: Effects of culture and cryopreservation and
      importance of short-term cell recovery.
AB  - BACKGROUND: Successful cell therapy relies on the identification and mass
      expansion of functional cells for infusion. Cryopreservation of cells is an
      inevitable step in most cell therapies which also entails consequences for the
      frozen cells. MATERIAL AND METHODS: This study assessed the impact of
      cryopreservation and the widely used protocol for rapid expansion of T
      lymphocytes. The effects on cell viability, immunocompetence and the impact on
      apoptotic and immunosuppressive marker expression were analyzed using validated
      assays. RESULTS AND CONCLUSION: Cryopreservation of lymphocytes during the rapid
      expansion protocol did not affect cell viability. Lymphocytes that underwent mass
      expansion or culture in high dose IL-2 were unable to respond to PHA stimulation
      by intracellular ATP production immediately after thawing (ATP = 16 +/- 11
      ng/ml). However, their reactivity to PHA was regained within 48 hours of recovery
      (ATP = 356 +/- 61 ng/ml). Analysis of mRNA levels revealed downregulation of TGF
      beta and IL-10 at all time points. Culture in high dose IL-2 led to upregulation
      of p73 and BCL-2 mRNA levels while FoxP3 expression was elevated after culture in
      IL-2 and artificial TCR stimuli. FoxP3 levels decreased after short-term recovery
      without IL-2 or stimulation. Antigen specificity, as determined by IFNgamma
      secretion, was unaffected by cryopreservation but was completely lost after
      addition of high dose IL-2 and artificial TCR stimuli. In conclusion, allowing
      short-time recovery of mass expanded and cryopreserved cells before reinfusion
      could enhance the outcome of adoptive cell therapy as the cells regain immune
      competence and specificity.

PMID- 23126548
TI  - Memory deficit associated with worse functional trajectories in older adults in
      low-vision rehabilitation for macular disease.
AB  - OBJECTIVES: To examine whether performance on a brief memory test is related to
      functional outcomes in older individuals undergoing low-vision rehabilitation
      (LVR) for macular disease. DESIGN: Observational cohort study of individuals
      receiving outpatient LVR. SETTING: Academic center. PARTICIPANTS: Ninety-one
      individuals (average age 80.1) with macular disease. MEASUREMENTS: Memory was
      assessed at baseline using a 10-word list; memory deficit was defined as
      immediate recall of two or fewer words. Vision-related function was measured
      using the 25-item Visual Function Questionnaire (VFQ-25) administered at baseline
      and during subsequent interviews (mean follow-up, 115 days). Linear mixed models
      were constructed to compare average trajectories of four VFQ-25 subscales: near
      activities, distance activities, dependency, and role difficulty. RESULTS: The
      29.7% of participants with memory deficits tended to decline in ability to
      accomplish activities that involved near vision. Controlling for age, sex, and
      education, the functional trajectory of participants with memory deficit differed
      significantly from that of those with better memory (P = .002), who tended to
      report improvements in ability to accomplish near activities. CONCLUSION: Of
      older adults receiving LVR for macular disease, those with memory deficits
      experienced worse functional trajectories in their ability to perform specific
      visually mediated tasks. A brief memory screen may help explain variability in
      rehabilitation outcomes and identify individuals who might require special
      accommodations.

PMID- 23126549
TI  - Evaluating the lethal and pre-lethal effects of a range of fungi against adult
      Anopheles stephensi mosquitoes.
AB  - BACKGROUND: Insecticide resistance is seriously undermining efforts to eliminate
      malaria. In response, research on alternatives to the use of chemical
      insecticides against adult mosquito vectors has been increasing. Fungal
      entomopathogens formulated as biopesticides have received much attention and have
      shown considerable potential. This research has necessarily focused on relatively
      few fungal isolates in order to 'prove concept'. Further, most attention has been
      paid to examining fungal virulence (lethality) and not the other properties of
      fungal infection that might also contribute to reducing transmission potential.
      Here, a range of fungal isolates were screened to examine variation in virulence
      and how this relates to additional pre-lethal reductions in feeding propensity.
      METHODS: The Asian malaria vector, Anopheles stephensi was exposed to 17
      different isolates of entomopathogenic fungi belonging to species of Beauveria
      bassiana, Metarhizium anisopliae, Metarhizium acridum and Isaria farinosus. Each
      isolate was applied to a test substrate at a standard dose rate of 1*109 spores
      ml-1 and the mosquitoes exposed for six hours. Subsequently the insects were
      removed to mesh cages where survival was monitored over the next 14 days. During
      this incubation period the mosquitoes' propensity to feed was assayed for each
      isolate by offering a feeding stimulant at the side of the cage and recording the
      number probing. RESULTS AND CONCLUSIONS: Fungal isolates showed a range of
      virulence to A. stephensi with some causing >80% mortality within 7 days, while
      others caused little increase in mortality relative to controls over the study
      period. Similarly, some isolates had a large impact on feeding propensity,
      causing >50% pre-lethal reductions in feeding rate, whereas other isolates had
      very little impact. There was clear correlation between fungal virulence and
      feeding reduction with virulence explaining nearly 70% of the variation in
      feeding reduction. However, there were some isolates where either feeding decline
      was not associated with high virulence, or virulence did not automatically prompt
      large declines in feeding. These results are discussed in the context of choosing
      optimum fungal isolates for biopesticide development.

PMID- 23126550
TI  - Highly ordered cubic mesoporous materials with the same symmetry but tunable pore
      structures.
AB  - In this article, two highly ordered mesoporous silica materials with the same
      face-centered cubic (fcc) symmetry but distinctly different pore structures have
      been synthesized by simply changing the amount of silica source. Their structures
      have been extensively studied by Synchrotron small-angle X-ray scattering, N(2)
      sorption analysis, scanning and transmission electron microscopy observations,
      and electron tomography. One mesoporous material formed by a hard sphere packing
      (HSP) pathway exhibits a bimodal pore distribution, while the other has a
      conventional FDU-12-type mesostructure with a single-sized pore. By increasing
      the amount of the silica source, the cavities formed by the packing of composite
      spherical micelles in the HSP mesostructure are gradually filled by the excess of
      siliceous species, leading to the conventional FDU-12-type mesostructure with the
      disappearance of bimodal pores. The pore connectivity of the HSP mesoporous
      material hydrothermally treated at 150  degrees C has been further investigated.
      Taking advantage of the ultrathin tomographic slices, the sizes of cage, cavity,
      and connectivity are measured to be 14.5, 10.5, and 6.4 nm, respectively. More
      importantly, the pore connection between the cage and cavity is directly observed
      to occur along the ?100? direction, different from the FDU-12-type mesostructure
      in which the connection appears between two adjacent cages along the ?110?
      direction. This work represents an unusual example where two ordered cage-type
      mesoporous materials with the same symmetry can be synthesized by slightly
      changing the synthesis condition, but their pore structures and pore connections
      are significantly different. Our finding is important for understanding the
      formation mechanism and for the rational design and controllable synthesis of
      novel mesoporous materials.

PMID- 23126551
TI  - Dispositional emotion coping styles and physiological responses to expressive
      writing.
AB  - OBJECTIVES: The purpose of these two studies was to assess how repressors and
      defensive, high-anxious individuals exhibit their psychological and health
      characteristics subjectively through self-reports and objectively through
      physiological markers and ratings of emotional expression. DESIGN: Cross
      sectional descriptive design (study one) and randomized controlled design (study
      two). METHODS: In the first descriptive study, repressors, defensive, high
      anxious individuals and low-anxious individuals were identified from a pool of
      748 undergraduates. Participants were asked to complete questionnaires assessing
      psychological and health characteristics. In the second experimental study, the
      three groups were randomized into either emotional or non-emotional writing
      conditions. Participants were asked to write three essays on either an emotional
      or a non-emotional topic in a single day. RESULTS: In the first study, defensive,
      high-anxious individuals reported significantly more distress, symptoms, sickness
      behaviours and difficulty expressing anger relative to repressors. In the second
      study, there was a significant difference in salivary cortisol concentrations
      between the two writing conditions regardless of the emotional coping grouping.
      Analysis of the writing showed no significant differences among repressors,
      defensive, high-anxious and low-anxious individuals in their cognitive and
      affective expression. CONCLUSIONS: Whereas self-reports of health outcomes and
      psychological traits clearly distinguish repressors and defensive, high-anxious
      individuals, more objective indices of emotional expressiveness and physiology do
      not appear to do so. The results also indicate that expressive writing may be
      helpful to reduce physiological arousal towards emotionally charged memories.

PMID- 23126552
TI  - Antibacterial and antifungal activities of Otanthus maritimus (L.) Hoffmanns. &
      Link essential oil from Sicily.
AB  - The chemical composition of the essential oil obtained from the flowers of
      Otanthus maritimus L., a perennial plant growing wild in maritime sands in the
      Mediterranean region, was investigated by GC and GC-MS analyses. Totally 66 were
      identified. The oil was dominated by the high content of monoterpene compounds,
      especially oxygenated monoterpenes which accounted for 73.1%. The most abundant
      components were yomogi alcohol (20.8%), camphor (15.8%), artemisyl acetate
      (15.3%) and artemisia alcohol (13.7%). The oil was tested against two Gram (+)
      and six Gram (-) bacterial strains, both American Type Culture Collection
      standard strains and clinically isolated (CI), one potentially pathogenic yeast
      (Candida albicans CI) and two filamentous phytopathogenic fungi (Botrytis cinerea
      and Rhizoctonia solani). The results show that the oil from O. maritimus exerts
      strong antibacterial and antifungal activities.

PMID- 23126553
TI  - Engineered nanomaterial risk. Lessons learnt from completed nanotoxicology
      studies: potential solutions to current and future challenges.
AB  - PARTICLE_RISK was one of the first multidisciplinary projects funded by the
      European Commission's Framework Programme that was responsible for evaluating the
      implications of nanomaterial (NM) exposure on human health. This project was the
      basis for this review which identifies the challenges that exist within the
      assessment of NM risk. We have retrospectively reflected on the findings of
      completed nanotoxicology studies to consider what progress and advances have been
      made within the risk assessment of NMs, as well as discussing the direction that
      nanotoxicology research is taking and identifying the limitations and failings of
      existing research. We have reflected on what commonly encountered challenges
      exist and explored how these issues may be resolved. In particular, the following
      is discussed (i) NM selection (ii) NM physico-chemical characterisation; (iii) NM
      dispersion; (iv) selection of relevant doses and concentrations; (v)
      identification of relevant models, target sites and endpoints; (vi) development
      of alternatives to animal testing; and (vii) NM risk assessment. These knowledge
      gaps are relatively well recognised by the scientific community and
      recommendations as to how they may be overcome in the future are provided. It is
      hoped that this will help develop better defined hypothesis driven research in
      the future that will enable comprehensive risk assessments to be conducted for
      NMs. Importantly, the nanotoxicology community has responded and adapted to
      advances in knowledge over recent years to improve the approaches used to assess
      NM hazard, exposure and risk. It is vital to learn from existing information
      provided by ongoing or completed studies to avoid unnecessary duplication of
      effort, and to offer guidance on aspects of the experimental design that should
      be carefully considered prior to the start of a new study.

PMID- 23126554
TI  - Pharmacological characterization of the 20% alcohol intermittent access model in
      Sardinian alcohol-preferring rats: a model of binge-like drinking.
AB  - BACKGROUND: Binge drinking is defined as a pattern of alcohol drinking that
      brings blood alcohol levels to 80 mg/dl or above. In this study, we
      pharmacologically characterized the intermittent access to 20% ethanol (EtOH)
      model (Wise, Psychopharmacologia 1973;29:203) in Sardinian alcohol-preferring
      (sP) rats to determine to which of the compounds known to reduce drinking in
      specific animal models this binge-like drinking was sensitive to. METHODS: Adult
      male sP rats were divided into 2 groups and allowed to drink either 20% v/v
      alcohol or water for 24 hours on alternate days (Monday, Wednesday, and Friday)
      or 10% v/v alcohol and water for 24 hours every day. After stabilization of their
      intake, both groups were administered 3 pharmacological agents with different
      mechanisms of action, naltrexone-an opioid receptor antagonist, SCH 39166-a
      dopamine D1 receptor antagonist, and R121919-a Corticotropin-Releasing Factor 1
      (CRF1 ) receptor antagonist, and their effects on alcohol and water intake were
      determined. RESULTS: Intermittent 20% alcohol ("Wise") procedure in sP rats led
      to binge-like drinking. Alcohol drinking was suppressed by naltrexone and by SCH
      39166, but not by R121919. Finally, naltrexone was more potent in reducing
      alcohol drinking in the intermittent 20% binge-drinking group than in the 10%
      continuous access drinking group. CONCLUSIONS: The Wise procedure in sP rats
      induces binge-like drinking, which appears opioid- and dopamine-receptor
      mediated; the CRF1 system, on the other hand, does not appear to be involved. In
      addition, our results suggest that naltrexone is particularly effective in
      reducing binge drinking. Such different pharmacological responses may apply to
      subtypes of alcoholic patients who differ in their motivation to drink, and may
      eventually contribute to treatment response.

PMID- 23126555
TI  - Risk of fractures in patients with multiple sclerosis: record-linkage study.
AB  - BACKGROUND: Patients with multiple sclerosis (MS) have been reported to be at
      higher risk of fracture than other people. We sought to test this hypothesis in a
      large database of hospital admissions in England. METHODS: We analysed a database
      of linked statistical records of hospital admissions and death certificates for
      the whole of England (1999-2010). Rate ratios for fractures were determined,
      comparing fracture rates in a cohort of all people in England admitted with MS
      and rates in a comparison cohort. RESULTS: Significantly elevated risk for all
      fractures was found in patients with MS (rate ratio (RR) = 1.99, 95% confidence
      interval (CI) = 1.93-2.05)). Risks were particularly high for femoral fractures
      (femoral neck fracture RR = 2.79 (2.65-2.93); femoral shaft fracture RR 6.69
      (6.12-7.29)), and fractures of the tibia or ankle RR = 2.81 (2.66-2.96).
      CONCLUSIONS: Patients with MS have an increased risk of fractures. Caregivers
      should aim to optimize bone health in MS patients.

PMID- 23126556
TI  - The adhesion modulation protein, AmpA localizes to an endocytic compartment and
      influences substrate adhesion, actin polymerization and endocytosis in vegetative
      Dictyostelium cells.
AB  - BACKGROUND: AmpA is a secreted 24Kd protein that has pleiotropic effects on
      Dictyostelium development. Null mutants delay development at the mound stage with
      cells adhering too tightly to the substrate. Prestalk cells initially specify as
      prespore cells and are delayed in their migration to the mound apex.
      Extracellular AmpA can rescue these defects, but AmpA is also necessary in a cell
      autonomous manner for anterior like cells (ALCs) to migrate to the upper cup. The
      ALCs are only 10% of the developing cell population making it difficult to study
      the cell autonomous effect of AmpA on the migration of these cells. AmpA is also
      expressed in growing cells, but, while it contains a hydrophobic leader sequence
      that is cleaved, it is not secreted from growing cells. This makes growing cells
      an attractive system for studying the cell autonomous function of AmpA. RESULTS:
      In growing cells AmpA plays an environment dependent role in cell migration.
      Excess AmpA facilitates migration on soft, adhesive surfaces but hinders
      migration on less adhesive surfaces. AmpA also effects the level of actin
      polymerization. Knockout cells polymerize less actin while over expressing cells
      polymerize more actin than wild type. Overexpression of AmpA also causes an
      increase in endocytosis that is traced to repeated formation of multiple
      endocytic cups at the same site on the membrane. Immunofluorescence analysis
      shows that AmpA is found in the Golgi and colocalizes with calnexin and the slow
      endosomal recycling compartment marker, p25, in a perinuclear compartment. AmpA
      is found on the cell periphery and is endocytically recycled to the perinuclear
      compartment. CONCLUSION: AmpA is processed through the secretory pathway and
      traffics to the cell periphery where it is endocytosed and localizes to what has
      been defined as a slow endosomal recycling compartment. AmpA plays a role in
      actin polymerization and cell substrate adhesion. Additionally AmpA influences
      cell migration in an environment dependent manner. Wild type cells show very
      little variation in migration rates under the different conditions examined here,
      but either loss or over expression of AmpA cause significant substrate and
      environment dependent changes in migration.

PMID- 23126557
TI  - Moment of inertia as a means to evaluate the biomechanical impact of pelvic organ
      prolapse.
AB  - OBJECTIVES: To present an alternative measure (moment of inertia) to describe the
      anatomical features of the pelvic organ prolapse. METHODS: A total of 30 women
      (21 diagnosed as having pelvic organ prolapse and 9 as controls) were evaluated
      by clinical scales and magnetic resonance imaging. Imaging biometric measures
      were carried out. Moment of inertia, pubovisceral muscle thickness and area, and
      levator hiatus anterior-to-posterior and lateral measures were compared by means
      of non-parametric tests, as well as their correlation with demographic features
      of the two sample groups. RESULTS: Moment of inertia, muscle area and levator
      hiatus diameters were statistically different between patients and controls.
      Furthermore, they were also well correlated with prolapse-associated factors,
      such as the number of vaginal deliveries and age, as well as Pelvic Organ
      Prolapse Quantification system and imaging staging of levator ani defects.
      CONCLUSIONS: Moment of inertia can be used as a new parameter to evaluate pelvic
      floor damage resulting from prolapse.

PMID- 23126558
TI  - Anti-cyclic citrullinated peptide antibodies: a comparison of different assays
      for the diagnosis of rheumatoid arthritis.
AB  - OBJECTIVES: Anti-cyclic citrullinated peptide (anti-CCP) antibodies are highly
      specific markers of rheumatoid arthritis (RA). Considering the heterogeneity of
      the target antigens involved, and the test platforms and conjugates proposed in
      commercial anti-CCP assays, we assessed the diagnostic performances of four fully
      automated anti-CCP assays in a cohort of patients with RA compared to patients
      with other autoimmune and inflammatory disorders. We also evaluated the agreement
      between the qualitative results of these immunoassays. METHOD: We evaluated three
      anti-CCP2 assays [Eurodiagnostica enzyme-linked immunosorbent assay (ELISA),
      Elecsys electrochemiluminescence immunoassay (ECLIA) on the Modular E170
      Analyzer, and Zenit chemiluminescence immunoassay (CLIA) on the Zenit RA
      Analyzer] and one anti-CCP3 assay (Inova ELISA). ELISAs were performed on an
      automated workstation. Samples from 112 patients with RA and a disease control
      group of 136 patients (53 with autoimmune diseases, 65 non-autoimmune disorders,
      and 18 infectious diseases) were studied (included 161 samples submitted
      consecutively to the laboratory). RESULTS: At a fixed specificity of 92%, the
      anti-CCP3 assay presented the highest sensitivity (75%) compared to the anti-CCP2
      assays evaluated (63-72%). The Zenit anti-CCP2 assay gave the most false-positive
      results (especially in patients with viral infections and connective tissue
      diseases). The agreement between assays ranged from 86.3% to 95.2% and Kappa
      coefficients ranged from 0.724 to 0.899. CONCLUSIONS: Recently released automated
      workstations provide a valuable alternative to ELISA to diagnose RA. However,
      differences in diagnostic performances are highlighted in our experience,
      especially for the Zenit assay. In our cohort, the anti-CCP3 assay gave slightly
      better performances than the anti-CCP2 assays (with the exception of the Zenit
      assay).

PMID- 23126559
TI  - Assessment of thiopurine methyltransferase activity in patients prescribed
      azathioprine or other thiopurine-based drugs.
AB  - OBJECTIVES: To examine whether pretreatment determination of thiopurine
      methyltransferase (TPMT) enzymatic activity (phenotyping) or TPMT genotype, to
      guide thiopurine therapy in chronic autoimmune disease patients, reduces
      treatment harms. Other objectives included assessing: preanalytic, analytic, and
      postanalytic requirements for TPMT testing; diagnostic accuracy of TPMT
      genotyping versus phenotyping; association of thiopurine toxicity with TPMT
      genotypic or phenotypic status; and costs of testing, care, and treating drug
      associated complications. DATA SOURCES: MEDLINE(r), EMBASE(r), and Healthstar
      were searched from inception to May 2010; the Cochrane Library(r) to October
      2009; and BIOSIS(r), Genetics Abstracts, and EconLitTM to May 2009, for English
      language records. REVIEW METHODS: A reviewer screened records, and a second
      reviewer verified exclusions and subsequent selection of relevant studies.
      Studies in patients with leukemia and organ transplant were excluded.
      Additionally, laboratories that provide TPMT analytical services were surveyed to
      assess means of TPMT testing in practice. Where possible, risk of bias was
      assessed using standard criteria. Meta-analyses estimated diagnostic sensitivity,
      and specificity; and odds ratios of associations. RESULTS: 1790 titles or
      abstracts, and 538 full text records were screened. 114 observational studies and
      one RCT were included. Majority of studies were rated fair quality, except for
      diagnostic studies with 37 percent of studies rated poor. In general, there were
      few patients who were homozygous (or compound heterozygous) for TPMT variant
      alleles in the included studies limiting applicability.  There is insufficient
      evidence examining effectiveness of pretesting in terms of reduction in clinical
      adverse events.  Sufficient preanalytical data were available regarding preferred
      specimen collection, stability and storage conditions for TPMT testing. There was
      no clinically significant effect of age, gender, various coadministered drugs, or
      most morbidities (with the exception of renal failure and dialysis). TPMT
      phenotyping methods had coefficients of variation generally below 10 percent.
      TPMT genotyping reproducibility is generally between 95-100 percent.  The
      sensitivity of genotyping to identify patients with low or intermediate TPMT
      enzymatic activity is imprecise, ranging from 70.70 to 82.10 percent (95 percent
      CI, lower bound range 37.90 to 54.00 percent; upper bound range 84.60 to 96.90
      percent). Sensitivity of homozygous TPMT genotype to correctly identify patients
      with low to absent enzymatic activity was 87.10 percent (95 percent CI 44.30 to
      98.30 percent). Genotyping specificity approached 100 percent.  Leukopenia was
      significantly associated with low and intermediate enzymatic activity (low
      activity OR 80.00, 95 percent CI 11.5 to 559; and intermediate activity OR 2.96,
      95 percent CI 1.18 to 7.42), and homozygous and heterozygous TPMT variant allele
      genotype (OR 18.60, 95 percent CI 4.12 to 83.60; and 4.62, 95 percent CI 2.34 to
      9.16, respectively). In general, TPMT phenotyping costs less than genotyping,
      although estimates across studies are quite heterogeneous. CONCLUSIONS: There is
      insufficient direct evidence regarding the effectiveness of pretesting of TPMT
      status in patients with chronic autoimmune diseases. Indirect evidence confirms
      strong association of leukopenia with lower levels of TPMT activity and carrier
      genotype already established in the literature.

PMID- 23126560
TI  - Chemical speciation of Fe and Ni in residual oil fly ash fine particulate matter
      using X-ray absorption spectroscopy.
AB  - Epidemiological studies have linked residual oil fly ash fine particulate matter
      with aerodynamic diameter <2.5 MUm (ROFA PM(2.5)) to morbidity and mortality from
      cardiovascular and respiratory illnesses. Bioavailable transition metals within
      PM have been cited as one of the components that induce such illnesses. By
      combining synchrotron-based X-ray absorption spectroscopy with leaching
      experiment, we studied the effect of residual oil compositions and combustion
      conditions on the speciation of Fe and Ni in ROFA PM(2.5) and the implication of
      these species for human health and environment. PM(2.5) samples were obtained
      from two types of combustors, a fire tube boiler (FTB) and a refractory line
      combustor (RLC). The study reveals that only Fe(2)(SO(4))(3).nH(2)O is present in
      RLC PM(2.5) while Fe(2)(SO(4))(3).nH(2)O predominates in FTB PM(2.5) with
      inclusion of varying amounts of nickel ferrite. The finding that RLC PM(2.5) is
      more bioavailable and hence more toxic than FTB PM(2.5) is significant. The
      reduction of toxicity of FTB PM(2.5) is due to the immobilization of a portion of
      Fe and Ni in the formation of an insoluble NiFe(2)O(4). This may explain the
      variation of toxicity from exposure to different ROFA PM(2.5). Additionally, the
      speciation data are sought for developing emission inventories for source
      apportionment study and understanding the mechanism of PM formation.

PMID- 23126561
TI  - 31P-edited diffusion-ordered 1H NMR spectroscopy for the spectral isolation and
      identification of organophosphorus compounds related to chemical weapons agents
      and their degradation products.
AB  - Organophosphorus compounds represent a large class of molecules that include
      pesticides, flame-retardants, biologically relevant molecules, and chemical
      weapons agents (CWAs). The detection and identification of organophosphorus
      molecules, particularly in the cases of pesticides and CWAs, are paramount to the
      verification of international treaties by various organizations. To that end,
      novel analytical methodologies that can provide additional support to traditional
      analyses are important for unambiguous identification of these compounds. We have
      developed an NMR method that selectively edits for organophosphorus compounds via
      (31)P-(1)H heteronuclear single quantum correlation (HSQC) and provides an
      additional chromatographic-like separation based on self-diffusivities of the
      individual species via (1)H diffusion-ordered spectroscopy (DOSY): (1)H-(31)P
      HSQC-DOSY. The technique is first validated using the CWA VX (O-ethyl S-[2
      (diisopropylamino)ethyl] methylphosphonothioate) by traditional two-dimensional
      DOSY spectra. We then extend this technique to a complex mixture of VX
      degradation products and identify all the main phosphorus-containing byproducts
      generated after exposure to a zinc-cyclen organometallic homogeneous catalyst.

PMID- 23126562
TI  - Liver transplantation outcome in patients with angiographically proven coronary
      artery disease: a multi-institutional study.
AB  - Over the last decade the age of liver transplant (LT) recipients and the
      likelihood of coronary artery disease (CAD) in this population have increased.
      There are no multicenter studies that have examined the impact of CAD on LT
      outcomes. In this historical cohort study, we identified adult LT recipients who
      underwent angiography prior to transplantation at seven institutions over a 12
      year period. For each patient we recorded demographic data, recipient and donor
      risk factors, duration of follow-up, the presence of angiographically proven
      obstructive CAD (>=50% stenosis) and post-LT survival. Obstructive CAD was
      present in 151 of 630 patients, the CAD(+) group. Nonobstructive CAD was found in
      479 patients, the CAD(-) group. Patient survival was similar for the CAD(+) group
      (adjusted HR 1.13, CI = [0.79, 1.62], p = 0.493) compared to the CAD(-) group.
      The CAD(+) patients were further stratified into severe (CADsev, >70% stenosis, n
      = 96), and moderate CAD (CADmod, 50-70% stenosis, n = 55) groups. Survival for
      the CADsev (adjusted HR = 1.26, CI = [0.83, 1.91], p = 0.277) and CADmod
      (adjusted HR = 0.93, CI = [0.52, 1.66], p = 0.797) groups were similar to the
      CAD(-) group. We conclude that when current CAD treatment strategies are employed
      prior to transplant, post-LT survival is not significantly different between
      patients with and without obstructive CAD.

PMID- 23126563
TI  - The role of personality in predicting repeat participation in periodic health
      screening.
AB  - OBJECTIVE: Drawing on the Five-Factor Model of personality, the aim of the
      present study was to find out which personality traits predict health maintenance
      behaviors, reflected in routine participation in health screenings, over and
      above objective and subjective health status. METHOD: Participants were 2,803
      employed individuals (61% men), free of background diseases, who underwent a
      routine health examination and were subsequently notified whether they were
      healthy or at risk. These participants were invited to repeat the examination
      within the next few years, as is medically recommended. RESULTS: Logistic and
      negative binomial regressions were used to predict participants' odds of
      returning for a second examination, within the next 7 years, as well as the
      number of consecutive visits, while controlling for sociodemographic factors,
      objective and subjective health, and length of follow-up. We found that both
      endpoints were positively predicted by Conscientiousness and negatively predicted
      by Extraversion and Openness. The association between Neuroticism and these
      endpoints followed a bell-shaped curve (i.e., individuals high or low in
      Neuroticism were less likely to return). CONCLUSIONS: The present findings
      suggest that personality traits should be taken into consideration in the
      planning and implementation of health-promoting interventions.

PMID- 23126564
TI  - Antigenicity and epitope specificity of ZnT8 autoantibodies in type 1 diabetes.
AB  - The single nucleotide polymorphism (SNP) rs13266634 encodes either an Arginine
      (R) or a Tryptophan (W) (R325W) at the amino acid position 325 in the Zinc
      Transporter 8 (ZnT8) protein. Autoantibodies (Ab) that recognize ZnT8R, ZnT8W or
      both at the polymorphic site are common in newly diagnosed type 1 diabetes (T1D)
      patients. The epitope specificity and affinity of ZnT8Ab are poorly understood,
      but may be of importance for the prediction and clinical classification of T1D.
      Therefore, the aims were to 1) determine the immunogenicity of short (318-331)
      ZnT8 peptides in mice and 2) test the affinity of short and long (268-369) ZnT8
      proteins in T1D patients positive for either ZnT8RAb or ZnT8wAb. Sera from
      BALB/cByJ mice immunized with short R, W or Q (Glutamine) ZnT8 peptides were
      tested for ZnT8-peptide antibodies in ELISA and radiobinding assay (RBA). Using
      reciprocal permutation experiment, short synthetic ZnT8R and ZnT8W (318-331) and
      long in vitro transcription translation ZnT8R and ZnT8W (268-369) proteins were
      tested in competitive RBA with R- and W-monospecific T1D sera samples. All mouse
      sera developed non-epitope-specific peptide antibodies in ELISA and only 6/12
      mice had ZnT8-RWQ antibodies in RBA. Both long ZnT8R and ZnT8W (268-369), but not
      any short, proteins displaced labelled ZnT8 (268-369) proteins in binding to T1D
      ZnT8Ab-specific sera. The reciprocal cross-over tests showed that half-maximal
      displacement varied 2- to 11-fold indicating variable affinity of patient ZnT8Ab,
      signifying crucial autoantibody epitope spreading. The present approach should
      make it possible to dissect the importance of the R325W ZnT8 autoantigen epitope
      in the T1D pathogenesis.

PMID- 23126565
TI  - Bending benzene: syntheses of [n]cycloparaphenylenes.
AB  - Since the first successful synthesis in 2008, methods to prepare the
      [n]cycloparaphenylenes have evolved rapidly. The aim of this synopsis is to
      provide an overview of recent advancements in this emerging field. The
      optoelectronic properties and supramolecular chemistry of these unique structures
      are presented as well.

PMID- 23126567
TI  - Lagniappe: the impact of headache disorders in America.
AB  - The immense burden of headache disorders in America has been very rarely
      considered during the formal deliberations of Congress. On February 14, 2012, the
      Committee on Health, Education, Labor, and Pensions of the United States Senate
      held a public hearing on Pain in America: Exploring Challenges to Relief. During
      that hearing, Senator Bernard Sanders of Vermont entered into the Congressional
      Record testimony on the impact of headache disorders on behalf of the Alliance
      for Headache Disorders Advocacy.

PMID- 23126566
TI  - Residential proximity to nearest major roadway and cognitive function in
      community-dwelling seniors: results from the MOBILIZE Boston Study.
AB  - OBJECTIVES: To evaluate the association between residential distance to nearest
      major roadway, as a marker of long-term exposure to traffic pollution, and
      cognitive function in older adults. DESIGN: Prospective cohort study with median
      follow-up of 16.8 months. SETTING: Community. PARTICIPANTS: Seven hundred sixty
      five community-dwelling seniors. MEASUREMENTS: The Mini-Mental State Examination,
      Hopkins Verbal Learning Test-Revised (HVLT-R), Trail Making Test (TMT), category
      and letter fluency tests, and Clock-in-the-Box Test were administered during home
      visits on two occasions. The residential distance to the nearest major roadway
      was calculated, and generalized estimating equations were used to evaluate the
      association between performance on each test and residential distance to nearest
      major roadway, adjusting for participant demographics, education, socioeconomic
      status, and past medical history. RESULTS: Shorter distance to major roadway was
      associated with statistically significantly poorer performance on the immediate
      and delayed recall components of the HVLT-R, TMT Part B, TMT delta, and letter
      and category fluency tests. Generally, participants residing less than 100 m from
      a major roadway performed worst. Performance improved monotonically with
      increasing distance. CONCLUSION: In this cohort of community-dwelling older
      adults, residential proximity to a major roadway was associated with poorer
      performance on cognitive tests of verbal learning and memory, psychomotor speed,
      language, and executive functioning. If causal, these results add to the growing
      evidence that living near major roadways is associated with adverse health
      outcomes.

PMID- 23126568
TI  - Expression of recombinant HA1 protein for specific detection of influenza
      A/H1N1/2009 antibodies in human serum.
AB  - The hemagglutinin genes (HA1 subunit) from human and animal 2009 pandemic H1N1
      virus isolates were expressed with a baculovirus vector. Recombinant HA1 (rHA1)
      protein-based ELISA was evaluated for detection of specific influenza
      A(H1N1)pdm09 antibodies in serum samples from vaccinated humans. It was found
      that rHA1 ELISA consistently differentiated between antibodies recognizing the
      seasonal influenza H1N1 and pdm09 viruses, with a concordance of 94% as compared
      to the hemagglutination inhibition test. This study suggests the utility of rHA1
      ELISA in serosurveillance.

PMID- 23126569
TI  - Trimethylsilyl-terminated oligo(phenylene ethynylene)s: an approach to single
      molecule junctions with covalent Au-C sigma-bonds.
AB  - A new and efficient approach using cleaving of trimethylsilyl groups to create
      covalent Au-C anchoring sites has been developed for single-molecule junction
      conductance measurements. Employing the mechanically controllable break junction
      (MCBJ) technique in liquid, we demonstrate the formation of highly conducting
      single molecular junctions of several OPE derivatives. The created junctions are
      mechanically stable and exhibit conductances around one order of magnitude higher
      than those of their dithiol analogues. Extended assembly and reaction times lead
      to oligomerization. Combined STM imaging and gap-mode Raman experiments provide
      structure evidence to support the formation of covalent Au-C contacts and further
      oligomerization.

PMID- 23126570
TI  - Multiscale forward electromagnetic model of uterine contractions during
      pregnancy.
AB  - BACKGROUND: Analyzing and monitoring uterine contractions during pregnancy is
      relevant to the field of reproductive health assessment. Its clinical importance
      is grounded in the need to reliably predict the onset of labor at term and pre
      term. Preterm births can cause health problems or even be fatal for the fetus.
      Currently, there are no objective methods for consistently predicting the onset
      of labor based on sensing of the mechanical or electrophysiological aspects of
      uterine contractions. Therefore, modeling uterine contractions could help to
      better interpret such measurements and to develop more accurate methods for
      predicting labor. In this work, we develop a multiscale forward electromagnetic
      model of myometrial contractions during pregnancy. In particular, we introduce a
      model of myometrial current source densities and compute its magnetic field and
      action potential at the abdominal surface, using Maxwell's equations and a four
      compartment volume conductor geometry. To model the current source density at the
      myometrium we use a bidomain approach. We consider a modified version of the
      Fitzhugh-Nagumo (FHN) equation for modeling ionic currents in each myocyte,
      assuming a plateau-type transmembrane potential, and we incorporate the
      anisotropic nature of the uterus by designing conductivity-tensor fields.
      RESULTS: We illustrate our modeling approach considering a spherical uterus and
      one pacemaker located in the fundus. We obtained a travelling transmembrane
      potential depolarizing from -56 mV to -16 mV and an average potential in the
      plateau area of -25 mV with a duration, before hyperpolarization, of 35 s, which
      is a good approximation with respect to the average recorded transmembrane
      potentials at term reported in the technical literature. Similarly, the
      percentage of myometrial cells contracting as a function of time had the same
      symmetric properties and duration as the intrauterine pressure waveforms of a
      pregnant human myometrium at term. CONCLUSIONS: We introduced a multiscale
      modeling approach of uterine contractions which allows for incorporating
      electrophysiological and anatomical knowledge of the myometrium jointly. Our
      results are in good agreement with the values reported in the experimental
      technical literature, and these are potentially important as a tool for helping
      in the characterization of contractions and for predicting labor using
      magnetomyography (MMG) and electromyography (EMG).

PMID- 23126571
TI  - Investigation of the skin repair and healing mechanism of N-carboxymethyl
      chitosan in second-degree burn wounds.
AB  - N-carboxymethyl chitosan (NCMC) was synthesized with the modification of
      chitosan; the substitution degree was measured by titration. The biocompatibility
      and degradability of the NCMC were studied in vivo and the results showed that
      the NCMC was nontoxic and biocompatible. The in vivo degradation rate of NCMC in
      musculature was faster than that in subcutaneous tissue due to the relatively
      high lysozyme concentration. The NCMC was used as biomaterial to heal deep second
      degree burn wounds. The wound size reduction, histological examination, and the
      quantification of transforming growth factor-beta(1) , tumor necrosis factor
      alpha and interleukin-8 protein levels, and Smad3 gene expression were measured
      to evaluate the healing effects. The results demonstrated that the NCMC was
      efficient in accelerating wound healing via activating transforming growth factor
      beta(1) /Smad3 signaling pathway.

PMID- 23126572
TI  - Uterine fibroids affect pregnancy outcome in women over 30 years old: role of
      other risk factors.
AB  - OBJECTIVE: To evaluate the pregnancy outcome in women >30 years old with uterine
      fibroids also considering other possible concomitant risk factors. METHODS: A
      multicentric, observational and retrospective study was conducted. All women were
      asked to complete a questionnaire while they were in hospital and the outcome of
      pregnancy was investigated. RESULTS: Women with uterine fibroids before pregnancy
      were more frequently >35 years old and in their clinical history before pregnancy
      showed more pelvic pain, polliachiuria, previous pelvic surgery, hypermenorrhea
      and dysmenorrhea, than control women (p < 0.0001). During pregnancy patients with
      uterine fibroids showed significantly more threatened preterm birth (PTB) and
      PTB, weight gain, hyperemesis, gestational hypertension and post-partum bleeding
      and showed more often requirement for emergency cesarean section (p < 0.0001).
      The multivariate logistic regression model used for evaluating the effect of
      clinical parameters on outcome of pregnancy showed that age >35 years, pelvic
      pain, work, weight gain, hyperemesis, threatened miscarriage and threatened PTB
      were significantly correlated with unfavorable pregnancy outcome , independently
      of the presence of uterine fibroids (p < 0.0001). CONCLUSIONS: The present study
      confirming a more frequent negative pregnancy outcome in presence of uterine
      fibroids, showed that other risk factors may affect pregnancy and delivery
      outcome in women aging >30 years old.

PMID- 23126573
TI  - Hofmeister challenges: ion binding and charge of the BSA protein as explicit
      examples.
AB  - Experiments on bovine serum albumin (BSA) via potentiometric titration (PT) and
      electrophoretic light scattering (ELS) are used to study specific-ion binding.
      The effect is appreciable at a physiological concentration of 0.1 M. We found
      that anions bind to the protein surface at an acidic pH, where the protein
      carries a positive charge (Z(p) > 0), according to a Hofmeister series (Cl(-) <
      Br(-) < NO(3)(-) < I(-) < SCN(-)), as well as at the isoionic point (Z(p) = 0).
      The results obtained require critical interpretation. The measurements performed
      depend on electrostatic theories that ignore the very specific effects they are
      supposed to reveal. Notwithstanding this difficulty, we can still infer that
      different 1:1 sodium salts affect the BSA surface charge/pH curve because anions
      bind to the BSA surface with an efficiency which follows a Hofmeister series.

PMID- 23126574
TI  - Alcohol consumption and cancer risk: understanding possible causal mechanisms for
      breast and colorectal cancers.
AB  - OBJECTIVES: The purpose of this report is to systematically examine the possible
      causal mechanism(s) that may explain the association between alcohol (ethanol)
      consumption and the risk of developing breast and colorectal cancers. DATA
      SOURCES: We searched 11 external databases, including PubMed(r) and Embase, for
      studies on possible mechanisms. These searches used Medical Subject Headings and
      free text words to identify relevant evidence. REVIEW METHODS: Two reviewers
      independently screened search results, selected studies to be included, and
      reviewed each trial for inclusion. We manually examined the bibliographies of
      included studies, scanned the content of new issues of selected journals, and
      reviewed relevant gray literature for potential additional articles. RESULTS:
      Breast Cancer. Five human and 15 animal studies identified in our searches point
      to a connection between alcohol intake and changes in important metabolic
      pathways that when altered may increase the risk of developing breast cancer.
      Alterations in blood hormone levels, especially elevated estrogen-related
      hormones, have been reported in humans. Several cell line studies suggest that
      the estrogen receptor pathways may be altered by ethanol. Increased estrogen
      levels may increase the risk of breast cancer through increases in cell
      proliferation and alterations in estrogen receptors. Human studies have also
      suggested a connection with prolactin and with biomarkers of oxidative stress. Of
      15 animal studies, six reported increased mammary tumorigenesis (four
      administered a co-carcinogen and two did not). Other animal studies reported
      conversion of ethanol to acetaldehyde in mammary tissue as having a significant
      effect on the progression of tumor development.  Fifteen cell line studies
      suggested the following mechanisms:  Increased hormonal receptor levels.
      Increased cell proliferation. A direct stimulatory effect. DNA adduct formation.
      Increase cyclic adenosine monophosphate (camp). Change in potassium channels.
      Modulation of gene expression. Colorectal Cancer. One human tissue study, 19
      animal studies (of which 12 administered a co-carcinogen and seven did not), and
      10 cell line studies indicate that ethanol and acetaldehyde may alter metabolic
      pathways and cell structures that increase the risk of developing colon cancer.
      Exposure of human colonic biopsies to acetaldehyde suggests that acetaldehyde
      disrupts epithelial tight junctions.  Among 19 animal studies the mechanisms
      considered included:  Mucosal damage after ethanol consumption. Increased
      degradation of folate. Stimulation of rectal carcinogenesis. Increased cell
      proliferation. Increased effect of carcinogens. Ten cell line studies suggested: 
      Folate uptake modulation. Tumor necrosis factor modulation. Inflammation and cell
      death. DNA adduct formation. Cell differentiation. Modulation of gene expression.
      One study used a combination of animal and cell line and suggested intestinal
      cell proliferation and disruption of cellular signals as possible mechanisms.
      CONCLUSIONS: Based on our systematic review of the literature, many potential
      mechanisms by which alcohol may influence the development of breast or colorectal
      cancers have been explored but the exact connection or connections remain
      unclear. The evidence points in several directions but the importance of any one
      mechanism is not apparent at this time.

PMID- 23126576
TI  - Radiostereometric analysis of early implant migration - a valuable tool to ensure
      proper introduction of new implants.

PMID- 23126575
TI  - Early proximal migration of cups is associated with late revision in THA: a
      systematic review and meta-analysis of 26 RSA studies and 49 survivalstudies.
AB  - BACKGROUND AND PURPOSE: The association between excessive early migration of
      acetabular cups and late aseptic revision has been scantily reported. We
      therefore performed 2 parallel systematic reviews and meta-analyses to determine
      the association between early migration of acetabular cups and late aseptic
      revision. METHODS: One review covered early migration data from radiostereometric
      analysis (RSA) studies, while the other focused on revision rates for aseptic
      loosening from long-term survival studies. Thresholds for acceptable and
      unacceptable migration were classified according the Swedish Hip Arthroplasty
      Register and the Australian National Joint Replacement Registry: < 5% revision at
      10 years. RESULTS: Following an elaborate literature search, 26 studies
      (involving 700 cups) were included in the RSA review and 49 studies (involving
      38,013 cups) were included in the survival review. For every mm increase in 2
      year proximal migration, there was a 10% increase in revision rate, which
      remained after correction for age, sex, diagnosis, hospital type, continent, and
      study quality. Consequently, proximal migration of up to 0.2 mm was considered
      acceptable and proximal migration of 1.0 mm or more was considered unacceptable.
      Cups with proximal migration of between 0.2 and 1.0 mm were considered to be at
      risk of having revision rates higher than 5% at 10 years. INTERPRETATION: There
      was a clinically relevant association between early migration of acetabular cups
      and late revision due to loosening. The proposed migration thresholds can be
      implemented in a phased evidence-based introduction, since they allow early
      detection of high-risk cups while exposing a small number of patients.

PMID- 23126577
TI  - Searching the internet for help with pain: adolescent search, coping, and
      medication behaviour.
AB  - OBJECTIVES: To explore a community sample of adolescents for engagement with
      online pain resources. To assess if the use of the Internet to search for health
      information correlated with measures of coping, risk taking, catastrophizing
      about pain, and engaging in the self-management of pain. DESIGN: A cross
      sectional online study of community-based adolescents (n = 105) recruited via
      schools to examine their use of the Internet to seek pain-related information.
      METHODS: Adolescents completed questionnaires of pain coping, catastrophic
      thinking, risk-taking behaviour, and medication use. Descriptive analyses were
      undertaken on event rates of pertinent behaviours, principally on information
      seeking and pain management behaviour. Correlational analyses were undertaken
      between coping and information seeking, and medication use. RESULTS: Few
      participants engaged in online pain information seeking. Those who did were more
      likely to be female and scored higher on medication use, catastrophizing, risk
      taking, and the total score on the Pain Coping Questionnaire. CONCLUSIONS:
      Although adolescents are high users of the Internet, paradoxically they do not
      appear to use the Internet for information about pain and pain management.
      Further research should assess inhibitory and disinhibitory factors associated
      with information seeking about pain and chronic illness on the Internet.
      STATEMENT OF CONTRIBUTION: What is already known on this subject? Internet use in
      adolescents is common, mobile, and displays a level of technical awareness
      unparalleled by adults. The internet is postulated in previous research to
      present a platform for the delivery of health care, particularly information to
      aid health decision-making for young people. What does this study add? This study
      explores how adolescents use the internet to look for health information,
      particularly on pain and where this falls in a general profile of coping with
      illness. Interestingly and counterintuitively, adolescents did not use the
      internet to look for health or pain information. We hypothesize that there may be
      something about information on pain management that does not readily transfer to
      the digital world in a way that is useful to adolescent users.

PMID- 23126578
TI  - Chemical constituents of Machaerium hirtum Vell. (Fabaceae) leaves and branches
      and its anti-inflammatory activity evaluation.
AB  - Leaves and branches of Machaerium hirtum Vell. (Fabaceae), native to South
      America, were subjected to phytopharmacological investigation in order to
      identify its major chemical constituents and evaluate its extracts, fractions and
      isolated compounds in assays for anti-inflammatory activities. These were
      performed using mouse ear edema model, pleurisy and myeloperoxidase activity
      assays. Six compounds were isolated and identified as the flavanones swertisin
      and isovitexin, the alkaloid 4-hydroxy-N-methylproline, the triterpenes friedelin
      and lupeol, and the steroids sitosterol and stigmasterol. These compounds were
      identified by nuclear magnetic resonance of (1)H and (13)C data, in comparison
      with literature.

PMID- 23126579
TI  - Periodic extraction of interstitial fluid from the site of subcutaneous insulin
      infusion for the measurement of glucose: a novel single-port technique for the
      treatment of type 1 diabetes patients.
AB  - BACKGROUND: Treatment of type 1 diabetes patients could be simplified if the site
      of subcutaneous insulin infusion could also be used for the measurement of
      glucose. This study aimed to assess the agreement between blood glucose
      concentrations and glucose levels in the interstitial fluid (ISF) that is
      extracted from the insulin infusion site during periodic short-term interruptions
      of continuous subcutaneous insulin infusion (CSII). SUBJECTS AND METHODS: A
      perforated cannula (24 gauge) was inserted into subcutaneous adipose tissue of C
      peptide-negative type 1 diabetes subjects (n=13) and used alternately to infuse
      rapid-acting insulin (100 U/mL) and to extract ISF glucose during a fasting
      period and after ingestion of a standard oral glucose load (75 g). RESULTS:
      Although periodically interrupted for extracting glucose (every hour for
      approximately 10 min), insulin infusion with the cannula was adequate to achieve
      euglycemia during fasting and to restore euglycemia after glucose ingestion.
      Furthermore, the ISF-derived estimates of plasma glucose levels agreed well with
      plasma glucose concentrations. Correlation coefficient and median absolute
      relative difference values were found to be 0.95 and 8.0%, respectively. Error
      grid analysis showed 99.0% of all ISF glucose values within clinically acceptable
      Zones A and B (83.5% Zone A, 15.5% Zone B). CONCLUSIONS: Results show that ISF
      glucose concentrations measured at the insulin infusion site during periodic
      short-term interruptions of CSII closely reflect blood glucose levels, thus
      suggesting that glucose monitoring and insulin delivery may be performed
      alternately at the same tissue site. A single-port device of this type could be
      used to simplify and improve glucose management in diabetes.

PMID- 23126581
TI  - Studies assessing risk of treatments for diabetes mellitus and adverse pregnancy
      outcomes should control for known risk factors.

PMID- 23126582
TI  - Delayed small intestinal transit in patients with long-standing type 1 diabetes
      mellitus: investigation of the relationships with clinical features, gastric
      emptying, psychological distress, and nutritional parameters.
AB  - BACKGROUND: Studies on small intestinal transit in type 1 diabetes mellitus have
      reported contradictory results. This study assessed the orocecal transit time
      (OCTT) in a group of patients with type 1 diabetes mellitus and its relationships
      with gastrointestinal symptoms, glycemic control, chronic complications of
      diabetes, anthropometric indices, gastric emptying, small intestinal bacterial
      overgrowth (SIBO), and psychological distress. SUBJECTS AND METHODS: Twenty-eight
      patients with long-standing (>10 years) type 1 diabetes mellitus (22 women, six
      men; mean age, 39 +/- 9 years) participated in the study. The lactulose hydrogen
      breath test was used to determine OCTT and the occurrence of SIBO. The presence
      of anxiety and depression was assessed by the Hospital Anxiety and Depression
      scale. Gastric emptying was measured by scintigraphy. Anthropometric indices
      included body mass index, percentage body fat, midarm circumference, and arm
      muscle area. RESULTS: There was a statistically significant increase in OCTT
      values in diabetes patients (79 +/- 41 min) in comparison with controls (54 +/-
      17 min) (P=0.01). Individual analysis showed that OCTT was above the upper limit
      (mean+2 SD) in 30.8% of patients. All anthropometric parameters were
      significantly decreased (P<0.05) in patients with prolonged OCTT in comparison
      with those with normal OCTT. In contrast, there was no statistically significant
      association between prolonged OCTT and gastrointestinal symptoms, peripheral
      neuropathy, diabetic retinopathy, glycated hemoglobin, delayed gastric emptying,
      SIBO, anxiety, or depression. CONCLUSIONS: Small bowel transit may be delayed in
      about one-third of patients with long-standing type 1 diabetes mellitus. This
      abnormality seems to have a negative effect on nutritional status in these
      patients.

PMID- 23126583
TI  - A lactate dehydrogenase ELISA-based assay for the in vitro determination of
      Plasmodium berghei sensitivity to anti-malarial drugs.
AB  - BACKGROUND: Plasmodium berghei rodent malaria is a well-known model for the
      investigation of anti-malarial drug efficacy in vivo. However, the availability
      of drug in vitro assays in P. berghei is reduced when compared with the spectrum
      of techniques existing for Plasmodium falciparum. New alternatives to the current
      manual or automated methods described for P. berghei are attractive. The present
      study reports a new ELISA drug in vitro assay for P. berghei using two monoclonal
      antibodies against the parasite lactate dehydrogenase (pLDH). METHODS: This
      procedure includes a short-in vitro culture, the purification of schizonts and
      the further generation of synchronized mice infections. Early stages of the
      parasite are then incubated against different concentrations of anti-malarial
      drugs using micro-plates. The novelty of this procedure in P. berghei relies on
      the quantification of the drug activity derived from the amount of pLDH estimated
      by an ELISA assay using two monoclonal antibodies: 14C1 and 19G7. The IC50s
      obtained through the ELISA assay were compared with those from the micro-test.
      RESULTS: The initial parameters of the synchronized samples used in the in vitro
      assays were a parasitaemia of 0.5% and haematocrit of 1%, with an incubation
      period of 22 hours at 36.5 degrees C. pLDH detection using a 14C1 coating at 10
      MUg/ml and 19G7 at 2.5 * 10-3 MUg/ml provided good readouts of optical densities
      with low background in negative controls and specific detection levels for all
      parasite stages. IC50s values derived from the ELISA assay for artesunate,
      chloroquine, amodiaquine and quinine were: 15, 7, 2, and 144 nM, respectively.
      When artesunate and chloroquine IC50s were evaluated using the micro-test similar
      values were obtained. CONCLUSION: This ELISA-based in vitro drug assay is easy to
      implement, fast, and avoids the use radioisotopes or expensive equipment. The
      utility of this simple assay for screening anti-malarial drug activity against P.
      berghei in vitro is demonstrated.

PMID- 23126584
TI  - Regional variation in obstetrical intervention for hospital birth in the Republic
      of Ireland, 2005-2009.
AB  - BACKGROUND: Obstetrical interventions during childbirth vary widely across
      European and North American countries. Regional differences in intrapartum care
      may reflect an inpatient-based, clinician-oriented, interventional practice
      style. METHODS: Using nationally representative hospital discharge data, a
      retrospective cohort study was conducted to explore regional variation in
      obstetric intervention across four major regions (Dublin Mid Leinster; Dublin
      Northeast; South; West) within the Republic of Ireland. Specific focus was given
      to rates of induction of labour, caesarean delivery, epidural anaesthesia, blood
      transfusion, hysterectomy and episiotomy. Logistic regression analyses were
      performed to assess the association between geographical region and interventions
      while adjusting for patient case-mix. RESULTS: 323,588 deliveries were examined.
      The incidence of interventions varied significantly across regions; the greatest
      disparities were observed for rates of induction of labour and caesarean
      delivery. Women in the South had nearly two-fold odds of having prostaglandins
      (adjusted OR: 1.75, 95% CI 1.68-1.82), whereas women in the West had 1.85 odds
      (95% CI 1.77-1.93) of artificial rupture of membrane. Women delivering in the
      Dublin Northeast, South and West regions had more than two-fold increased odds of
      elective caesarean delivery relative to women delivering in the Dublin Mid
      Leinster region. The Dublin Northeast region had the highest odds of emergency
      caesarean delivery (adjusted OR: 1.36; 95% CI: 1.31-1.40). CONCLUSIONS:
      Substantial regional variation in intrapartum care was observed within this
      small, relatively homogeneous population. The association of intervention use
      with region illustrates the need to encourage uptake of scientific based practice
      guidelines to better inform clinical judgment.

PMID- 23126585
TI  - Association of RENAL nephrometry score with outcomes of minimally invasive
      partial nephrectomy.
AB  - OBJECTIVE: To evaluate the predictive value of the Radius, Exophytic, Nearness,
      Anterior, Location nephrometry scoring system and to investigate the influence of
      its individual components on perioperative outcomes of minimally invasive partial
      nephrectomy. METHODS: Consecutive laparoscopic partial nephrectomy (n = 189) and
      robotic partial nephrectomy (n = 109) cases from 2007 through 2011 were
      retrospectively reviewed from our prospectively maintained database. Urological
      surgeons assigned nephrometry scores, excluding cases without images available
      for review. The association of nephrometry score categories and individual
      components of the score to perioperative outcomes were assessed. RESULTS: No
      differences were observed in preoperative characteristics of low (n = 135),
      intermediate (n = 155) and high (n = 8) nephrometry groups. Higher nephrometry
      score was associated with an increased length of stay, estimated blood loss and
      warm ischemia time. Higher nephrometry scores were also associated with a greater
      proportion of major complications (P < 0.001). Distance to the renal sinus had
      the greatest impact on perioperative outcomes including operative and ischemic
      times, estimated blood loss, complications and length of stay. CONCLUSIONS: The
      Radius, Exophytic, Nearness, Anterior, Location nephrometry score has value as a
      predictive tool for perioperative outcomes of minimally invasive partial
      nephrectomy. Distance to the renal sinus seems to have the greatest association
      with outcomes. Using these findings, clinicians will be better able to counsel
      patients regarding anticipated perioperative outcomes of minimally invasive
      partial nephrectomy.

PMID- 23126586
TI  - Stress increases voluntary alcohol intake, but does not alter established
      drinking habits in a rat model of posttraumatic stress disorder.
AB  - BACKGROUND: Life-altering anxiety disorders, such as posttraumatic stress
      disorder (PTSD), can co-occur at high rates with substance use disorders.
      Alcoholism, compared with other substance use disorders, is particularly common.
      Rodent studies of acute stress effects on alcohol consumption show that stress
      can alter ethanol (EtOH) consumption. This study examined voluntary EtOH
      consumption in male Long-Evans rats that had undergone a stress-enhanced fear
      learning (SEFL) procedure. METHODS: Adult Long-Evans rats were exposed to a
      stress that consisted of 15 inescapable foot-shocks (1 mA, 1 second) known to
      cause a long-lasting nonassociative enhancement of subsequent fear learning.
      Control animals received no shock. One day later, animals were placed in a novel
      and very different context and received a single foot-shock. On day 3, animals
      were returned to the single shock context and freezing was used as a measure of
      learned fear. The intermittent access 2-bottle choice (2BC) regimen consisted of
      1 bottle of water and 1 bottle of experimental solution, either 19% EtOH or 28.4%
      sucrose-0.08% quinine, for a 24-hour period, 3 days a week, and all other times 2
      water bottles. This regimen lasted until stable levels of experimental solution
      drinking were reached, at which point the experimental solution was removed for
      40 days and then returned to measure the resumption of consumption. RESULTS: Rats
      that received stress prior to EtOH consumed significantly more EtOH than control
      rats before and after reinstatement. Rats that received stress after drinking was
      established did not consume significantly more EtOH when the drug was returned.
      Stress had no significant effect on sucrose-quinine drinking, our calorie and
      taste control for EtOH. CONCLUSIONS: A single traumatic event sufficient to
      produce long-lasting enhancement of fear learning increases voluntary EtOH
      consumption, but does not alter previously acquired EtOH drinking habits or alter
      the consumption of a calorically equivalent sweet-bitter-tasting solution.

PMID- 23126587
TI  - Smoking, low formal level of education, alcohol consumption, and the risk of
      rheumatoid arthritis.
AB  - OBJECTIVE: Suggested predictors of rheumatoid arthritis (RA) include
      environmental exposure, such as smoking. Our purpose was to investigate potential
      predictors of RA in a nested case-control study based on a prospective cohort.
      METHOD: Between 1991 and 1996, 30,447 persons were included in the Malmo Diet and
      Cancer Study (MDCS). Individuals who developed RA after inclusion up to 31
      December 2004 were identified by linking the database to different registers.
      Four controls were selected for every case. Data on lifestyle factors were
      collected in the MDCS. RESULTS: We identified 172 incident cases of RA [36
      men/136 women, mean age at diagnosis 63 years, 69% rheumatoid factor (RF)
      positive, median time from inclusion to diagnosis 5 (range 1-13) years]. In
      bivariate analyses, baseline smoking [odds ratio (OR) 2.02, 95% confidence
      interval (CI) 1.31-3.12] and a low level of formal education (i.e. <= 8 years; OR
      2.42, 95% CI 1.18-4.93 vs. University degree) predicted subsequent development of
      RA. Infrequent baseline alcohol consumption was a predictor of RA (OR 3.47, 95%
      CI 1.91-6.30) compared to recent use (within the past month), and individuals
      with moderate baseline alcohol consumption (3.5-15.2 g/day vs. < 3.5 g/day)
      tended to have a reduced risk of RA (OR 0.48, 95% CI 0.22-1.05) in multivariate
      analyses, adjusted for smoking and level of education. CONCLUSIONS: Smoking and a
      low level of formal education were found to be independent predictors of RA.
      Moderate alcohol consumption may also be associated with a reduced risk.

PMID- 23126588
TI  - Atmospheric fate of a series of carbonyl nitrates: photolysis frequencies and OH
      oxidation rate constants.
AB  - Multifunctional organic nitrates are potential NO(x) reservoirs whose atmospheric
      chemistry is somewhat little known. They could play an important role in the
      spatial distribution of reactive nitrogen species and consequently in ozone
      formation and distribution in remote areas. In this work, the rate constants for
      the reaction with OH radical and the photolysis frequencies of alpha
      nitrooxyacetone, 3-nitrooxy-2-butanone, and 3-methyl-3-nitrooxy-2-butanone have
      been determined at room temperature at 1000 mbar total pressure of synthetic air.
      The rate constants for the OH oxidation were measured using the relative rate
      technique, with methanol as reference compound. The following rate constants were
      obtained for the reaction with OH: k(OH) = (6.7 +/- 2.5) * 10(-13) cm(3)
      molecule(-1) s(-1) for alpha-nitrooxyacetone, (10.6 +/- 4.1) * 10(-13) cm(3)
      molecule(-1) s(-1) for 3-nitrooxy-2-butanone, and (2.6 +/- 0.9) * 10(-13) cm(3)
      molecule(-1) s(-1) for 3-methyl-3-nitrooxy-2-butanone. The corresponding
      photolysis frequencies extrapolated to typical atmospheric conditions for July
      first at noon at 40 degrees  latitude North were (4.8 +/- 0.3) * 10(-5) s(-1),
      (5.7 +/- 0.3) * 10(-5) s(-1), and (7.4 +/- 0.2) * 10(-5) s(-1), respectively. The
      data show that photolysis is a major atmospheric sink for these organic nitrates.

PMID- 23126589
TI  - Clinical and pathological effects of the polyopisthocotylean monogenean,
      Gamacallum macroura in white bass.
AB  - An aquaculture research facility experienced high mortality rates in white bass
      Morone chrysops associated with a monogenean infestation of the gills, but not in
      striped bass Morone saxatilis in the same facility. All mortalities had pale
      gills. Monogeneans, identified as Gamacallum macroura (MacCallum and MacCallum
      1913) Unnithan 1971, were found on the gills. Pale-gilled and healthy white bass
      were selected with no particular attention to condition for venipuncture and
      euthanasia for postmortem examination, including parasite counts from gills. The
      median packed cell volume (PCV) of fish with gill pallor was 12.5% (range 9-37%)
      while PVC of fish with more normal color was 30% (27-33%). Association between
      the PCV and gill pallor score was statistically significant, as was the
      association between PCV and the number of monogeneans found on the gills of each
      fish. Median estimated white blood cell count of fish with gill pallor, at 12.05
      * 10(3/)MUL (range 3.8-24.7), was significantly lower than of apparently healthy
      fish: 24.7 * 10(3)/MUL (17.3-31.5). Histopathology of the gill arches of pale
      gilled fish revealed multifocal moderate to severe branchitis, focal areas of
      dilated hyperplastic lamellae occluded by fibrin, and monogeneans attached to the
      lamellae. Fish that were apparently healthy had grossly similar histologic
      lesions, but at lower frequency and severity.

PMID- 23126590
TI  - Global gene expression of the inner cell mass and trophectoderm of the bovine
      blastocyst.
AB  - BACKGROUND: The first distinct differentiation event in mammals occurs at the
      blastocyst stage when totipotent blastomeres differentiate into either
      pluripotent inner cell mass (ICM) or multipotent trophectoderm (TE). Here we
      determined, for the first time, global gene expression patterns in the ICM and TE
      isolated from bovine blastocysts. The ICM and TE were isolated from blastocysts
      harvested at day 8 after insemination by magnetic activated cell sorting, and
      cDNA sequenced using the SOLiD 4.0 system. RESULTS: A total of 870 genes were
      differentially expressed between ICM and TE. Several genes characteristic of ICM
      (for example, NANOG, SOX2, and STAT3) and TE (ELF5, GATA3, and KRT18) in mouse
      and human showed similar patterns in bovine. Other genes, however, showed
      differences in expression between ICM and TE that deviates from the expected
      based on mouse and human. CONCLUSION: Analysis of gene expression indicated that
      differentiation of blastomeres of the morula-stage embryo into the ICM and TE of
      the blastocyst is accompanied by differences between the two cell lineages in
      expression of genes controlling metabolic processes, endocytosis, hatching from
      the zona pellucida, paracrine and endocrine signaling with the mother, and genes
      supporting the changes in cellular architecture, stemness, and hematopoiesis
      necessary for development of the trophoblast.

PMID- 23126591
TI  - Overexpression of human amyloidogenic light chains causes heart failure in
      embryonic zebrafish: a preliminary report.
AB  - AL cardiomyopathy leading to heart failure (HF) represents a significant cause of
      morbidity and mortality in systemic amyloidosis. However, the paucity of robust
      in vivo models of AL-induced cardiac dysfunction has limited our ability to probe
      the mechanisms of AL heart disease. To address this problem, we have developed a
      model of AL HF in zebrafish embryos by injection of in vitro transcribed mRNA
      encoding amyloidogenic light chain (aLC) into fertilized oocytes. We demonstrate
      that expression of aLC causes cardiomyopathy in developing zebrafish without
      significantly impairing extracardiac development. The cardiac ventricle of
      embryos expressing aLC exhibit impaired contractility, smaller size, and
      increased myocardial thickness which result in congestion and edema, features
      paralleling the clinical manifestations of amyloid cardiomyopathy. Phosphorylated
      p38, a marker of oxidative stress, was increased in response to aLC expression.
      No evidence of amyloid fibril deposition was identified. Thus, expression of aLC
      mRNA in zebrafish results in cardio toxic effects without fibril deposition. This
      is consistent with prior evidence indicating that aLC oligomers mediate cardiac
      dysfunction in vitro. This model will allow exploration of amyloid
      pathophysiology and testing of interventions to reduce and reverse the
      deleterious effects of amyloidosis on myocardial function.

PMID- 23126592
TI  - A transthyretin variant, Asp18Asn, associated with amyloid cardiomyopathy: a new
      African-American variant?
AB  - In this report, we describe the clinical features of a transthyretin (TTR) gene
      mutation (Asp18Asn) in a 54-year-old Liberian male presenting with congestive
      heart failure due to amyloid cardiomyopathy, in the absence of neurologic
      impairment. Review of the literature revealed only two other documented cases of
      this mutation, neither of whom was described in any detail. Follow-up information
      on these cases revealed that they were of African origin, as was one other
      unpublished case. We therefore believe that this is the second TTR mutation
      associated with isolated cardiac manifestations to be described in patients of
      African origin. It appears to be far less common than the previously described
      Val122Ile mutation but onset may be at an earlier age, potentially making heart
      transplantation a viable option should heart failure become severe.

PMID- 23126593
TI  - Reducing early exposure to calcineurin inhibitors: the key factor for a
      successful renal sparing strategy.

PMID- 23126594
TI  - Management of Acute Otitis Media: update.
AB  - CONTEXT: Acute Otitis Media (AOM), a viral or bacterial infection of the ear, is
      the most common childhood infection for which antibiotics are prescribed in the
      United States. In 2001, the Southern California Evidence-based Practice Center
      conducted a systematic review of the evidence comparing treatments of AOM.
      OBJECTIVES: This review updates the 2001 review findings on diagnosis and
      treatment of uncomplicated AOM, assesses the evidence for treatment of recurrent
      AOM, and assesses the impact of the heptavalent pneumococcal conjugate (PCV7)
      vaccine on the microbiology of AOM. DATA SOURCES AND STUDY SELECTION: Searches of
      PubMed(r) and the Cochrane databases were conducted from January 1998 to July
      2010 using the same search strategies used for the 2001 report, with the addition
      of terms not considered in the 2001 review. The Web of Science was also searched
      for citations of the 2001 report and its peer-reviewed publications. DATA
      EXTRACTION: After review by two investigators against pre-determined
      inclusion/exclusion criteria, we included existing systematic reviews and
      randomized controlled clinical trials for assessment of treatment efficacy and
      safety. Pooled analysis was performed for comparisons with three or more trials.
      RESULTS AND CONCLUSIONS: Few studies were found that examined the accuracy and
      precision of the diagnosis of AOM. Since PCV7's introduction, AOM microbiology
      has shifted significantly, with Streptococcus pneumoniae becoming less prevalent
      and Haemophilus influenzae (HF) increasing in importance. For uncomplicated AOM,
      pooled analysis indicates that nine children (95% CI: 6, 20) would need to be
      treated with ampicillin or amoxicillin rather than placebo to note a difference
      in the rate of clinical success. However, in four studies of delayed treatment
      approaches for uncomplicated AOM, two had higher rates of clinical success with
      immediate antibiotic therapy while two did not, and in three studies, a marked
      decrease in antibiotic utilization was noted. We are unable to draw definitive
      conclusions regarding the comparative effectiveness of different antibiotics for
      AOM in children with recurrent otitis media (ROM). For ROM, long-term antibiotic
      administration will decrease AOM episodes from 3 to 1.5 for every 12 months of
      treatment per otitis prone child during active treatment (95% CI: 1.2, 2.1);
      however, potential consequences of long-term treatment need to be considered.
      Data were insufficient to draw conclusions about comparative effectiveness of
      different treatment strategies in subgroups of children with uncomplicated AOM.
      Adverse events were generally more frequent for amoxicillin-clavulanate than for
      cefdinir, ceftriaxone, or azithromycin. Higher quality studies and improved
      reporting of study characteristics related to quality are needed to provide
      definitive conclusions for AOM and ROM treatment options.

PMID- 23126595
TI  - It's not just what we encode, but how we encode it: associations between
      neuroticism and learning.
AB  - OBJECTIVE: Neuroticism is a strong predictor of future mental health problems.
      The informativeness of this association has been questioned because of the
      limited understanding of the mechanisms underlying Neuroticism. In this article
      the authors extend our understanding of the association between information
      processing and Neuroticism. METHOD: Two independent studies involving separate
      sets of college students (N = 89 and N = 33), use self-rated Neuroticism scores
      to compare individuals' ability to learn simple and more complex discriminations,
      between simple shapes and words presented alone and in compound. RESULTS:
      Neuroticism was found to be associated with differences in learning to
      discriminate simple stimuli from compounds containing the same simple stimuli.
      Individuals with high levels of Neuroticism appeared to process compounds of
      stimuli as whole units even when this ceased to be an effective strategy for
      learning. In contrast, individuals with lower levels of Neuroticism performed
      better with discriminations that could be solved while learning about separate
      stimuli, rather than compounds. CONCLUSIONS: The authors discuss possible
      mechanisms of learning identified by these tasks and consider what implications
      their observations have for an understanding of the relationship between
      Neuroticism and mental health problems.

PMID- 23126596
TI  - Total synthesis of the proposed structure of 8-deshydroxyajudazol A: a modified
      approach to 2,4-disubstituted oxazoles.
AB  - The total synthesis of the proposed structure for the minor myxobacterial
      metabolite 8-deshydroxyajudazol A (3) is described. The isochromanone moiety
      present in the eastern fragment was constructed by an intramolecular-Diels-Alder
      (IMDA). Difficulties were encountered with the formation of the 2,4-disubstituted
      oxazole, so this was synthesized via a modified approach. This involved selective
      acylation of the diol 7 with acid 8, azide displacement of the secondary alcohol,
      and subsequent azide reduction in the presence of base which induced an O,N shift
      to give the hydroxyamide 23. Cyclodehydration then gave the desired oxazole 24
      and deprotection followed by mesylation and elimination produced the C15 alkene
      5. Sonogashira coupling with the eastern fragment vinyl iodide 6 and partial
      reduction yielded 8-deshydroxyajudazol A (3).

PMID- 23126597
TI  - Headache direction and aura predict migraine responsiveness to rimabotulinumtoxin
      B.
AB  - OBJECTIVE: To report a retrospective analysis of patients with migraine headaches
      treated with rimabotulinumtoxin B as preventive treatment, investigating an
      association between clinical responsiveness with migraine directionality and
      migrainous aura. BACKGROUND: The Phase III Research Evaluating Migraine
      Prophylaxis Therapy studies demonstrated onabotulinumtoxin A is effective in the
      preventive management of chronic migraine headaches. Jakubowski et al reported
      greater response to onabotulinumtoxin A in migraine patients reporting inward
      directed head pain (imploding or ocular) compared with outward-directed head pain
      (exploding), suggesting subpopulations of patients may be better candidates for
      its use. No correlation was found between those reporting migrainous aura and
      onabotulinumtoxin A responsiveness. METHODS: One hundred twenty-eight migraine
      patients were identified who had received rimabotulinumtoxin B injections over an
      average of 22 months, or 7 injection cycles. Migraine directionality was reported
      as inward directed (imploding, n = 72), eye centered (ocular, n = 28), outward
      directed (exploding, n = 16), and mixed (n = 12). RESULTS: One hundred two out of
      one hundred twenty-eight patients (80%) improved; of these, 58 (57%) demonstrated
      a >75% reduction in monthly headache frequency (">75%-responders"), 76% of which
      noted sustained benefits >12 months with repeated injections every 10-12 weeks.
      Those reporting ocular- and imploding-directed headaches were significantly more
      likely to be >75%-responders, compared with exploding- and mixed-directed
      headaches (P < .0025). Patients with ocular-directed headaches were most likely
      to be sustained >75%-responders. Patients reporting migrainous aura were more
      likely to be >75%-responders (P = .0007). Those reporting exploding- and mixed
      directed headaches were more likely to be nonresponders (P < .0001). CONCLUSIONS:
      Reported migraine directionality and presence of migrainous aura predict migraine
      headache responsiveness to rimabotulinumtoxin B injections.

PMID- 23126598
TI  - Influenza immunization in older adults with and without cancer.
AB  - OBJECTIVES: To compare the likelihood of receiving an influenza immunization in
      older adults before and immediately after a cancer diagnosis occurring in 2001
      and for the same time periods with older adults not diagnosed with cancer.
      DESIGN: Retrospective analysis comparing influenza immunization rates of Medicare
      beneficiaries with and without a diagnosis of cancer. SETTING: Surveillance,
      Epidemiology, and End Results-Medicare Data. PARTICIPANTS: Propensity score
      matching matched a group of 35,229 persons without cancer with 35,257 individuals
      diagnosed with cancer in 2001. MEASUREMENTS: Receipt of influenza vaccination
      based upon Medicare Claims Data. RESULTS: A difference-of-difference analysis
      revealed that influenza immunization rates increased over time for persons
      diagnosed with cancer (46.8% before to 50.8% after cancer diagnosis), but the
      increase was greater in beneficiaries without a cancer diagnosis (42.6% to 79.7%)
      (P < .001; 95% confidence interval = 0.320-0.324). Logistic regression analysis
      revealed that individuals without a cancer diagnosis were 7.25 times as likely to
      receive an influenza immunization. CONCLUSION: Older adults who have been
      recently diagnosed with cancer receive influenza immunizations at much lower
      rates than older adults who have not been diagnosed with cancer despite
      interaction with healthcare providers. Opportunities exist to improve influenza
      immunization in this population, who are susceptible to influenza because of
      compromised immune systems.

PMID- 23126599
TI  - The ex vivo induction of human CD103+ CD25hi Foxp3+ CD4+ and CD8+ Tregs is IL-2
      and TGF-beta1 dependent.
AB  - The expression of the integrin alphaE (CD103), may enhance the retention of
      regulatory T cells to peripheral inflammatory sites and possibly contribute to
      their suppressive potential. The aim of this study was to define the regulatory
      role of IL-2 and TGF-beta1 on the CD103 expression and the optimal in vitro
      conditions for the induction/expansion of human CD4(+) and CD8(+) Tregs. Cord
      blood mononuclear cells (CBMC) were stimulated under various culture conditions,
      including anti-CD3, anti-CD28, IL-2 and TGF-beta1. TGF-beta1 and IL-2 were both
      required for optimal expression of CD103. In addition, TGF-beta1 and IL-2
      synergistically induced CD103 expression on CD8(+) T cells, whereas, only
      additive induced expression was noted on CD4(+) T cells. Surprisingly, CD103
      expression was not dependent upon CD28 costimulation. IL-2 also played a central
      role in CD103 expression by CD25(hi) Foxp3+ Tregs. IL-2, TGF-beta1 and anti-CD3
      defined the optimal stimulatory conditions favouring the induction/expansion of
      both CD4(+) and CD8(+) human Tregs from naive CBMC. Thus, this study provides new
      insights into the regulatory role of IL-2 upon CD103 expression by human cord
      blood CD4(+) and CD8(+) T cells. Furthermore, it identifies the in vitro culture
      conditions driving the differentiation of the novel phenotype CD4(+) and CD8(+)
      CD103(+) CD25(hi) Foxp3+ Tregs from human CBMC.

PMID- 23126600
TI  - The Multi-Leu peptide inhibitor discriminates between PACE4 and furin and
      exhibits antiproliferative effects on prostate cancer cells.
AB  - The proprotein convertases (PCs) play an important role in protein precursor
      activation through processing at paired basic residues. However, significant
      substrate cleavage redundancy has been reported between PCs. The question remains
      whether specific PC inhibitors can be designed. This study describes the
      identification of the sequence LLLLRVKR, named Multi-Leu (ML)-peptide, that
      displayed a 20-fold selectivity on PACE4 over furin, two enzymes with similar
      structural characteristics. We have previously demonstrated that PACE4 plays an
      important role in prostate cancer and could be a druggable target. The present
      study demonstrates that the ML-peptide significantly reduced the proliferation of
      DU145 and LNCaP prostate cancer-derived cell lines and induced G0/G1 cell cycle
      arrest. However, the ML-peptide must enter the cell to inhibit proliferation. It
      is concluded that peptide-based inhibitors can yield specific PC inhibitors and
      that the ML-peptide is an important lead compound that could potentially have
      applications in prostate cancer.

PMID- 23126601
TI  - The influence of electromyographic biofeedback therapy on knee extension
      following anterior cruciate ligament reconstruction: a randomized controlled
      trial.
AB  - BACKGROUND: Loss of knee extension and a deficit in quadriceps strength are
      frequently found following anterior cruciate ligament (ACL) reconstruction. The
      aim of this study was to investigate whether the addition of Eletromyographic
      Biofeedback (EMG BFB) therapy for the vastus medialis muscle to the in the early
      phase of the standard rehabilitation programme could improve the range of knee
      extension and strength after ACL reconstruction more than a standard
      rehabilitation programme. The correlation between EMG measurement and passive
      knee extension was also investigated. METHOD: Sixteen patients, all of whom
      underwent endoscopic ACL reconstruction using patellar tendon autograft, were
      randomly assigned to two groups:* Control group (8 patients): standard
      rehabilitation protocol; with full weight-bearing postoperative, knee brace (0
      degrees  extension, 90 degrees  flexion), electrical stimulation, aquatics and
      proprioceptive training.* The EMG BFB group (8 patients): EMG BFB was added to
      the standard rehabilitation protocol within the first postoperative week and
      during each session for the next 6 weeks.Each patent attended a total of 16
      outpatient physiotherapy sessions following surgery. High-Heel-Distance (HHD)
      Test, range of motion (ROM) and integrated EMG (iEMG) for vastus medialis were
      measured preoperatively, and at the 1, 2, 4 and 6-week follow ups. Additionally,
      knee function, swelling and pain were evaluated using standardized scoring
      scales. RESULTS: At 6 weeks, passive knee extension (p < 0.002) and the HHD Test
      were significantly (p < 0.01) better in the EMG BFB group compared to controls.
      Integrated EMG (vastus medialis) of the EMG BFB group also showed a significant
      increase after 2 (p < 0.01) and 6 (p < 0.01) weeks. At the 6-week follow up, no
      significant (p > 0.01) differences were found between the two groups for the
      assessment of knee function, swelling and pain. CONCLUSION: The results indicate
      that EMG BFB therapy, in the early phase of rehabilitation after ACL
      reconstruction, is useful in enhancing knee extension. Improved innervation of
      the vastus medialis can play a key role in the development of postoperative knee
      extension. EMG BFB therapy is a simple, inexpensive and valuable adjunct to
      conventional therapeutic modalities.

PMID- 23126602
TI  - Shape-controlled synthesis of PbS nanocrystals via a simple one-step process.
AB  - A one-step colloidal process was adopted to prepare face-centered-cubic PbS
      nanocrystals with different shapes such as octahedral, starlike, cubic, truncated
      octahedral, and truncated cubic. The features of this approach avoid the
      presynthesis of any organometallic precursor and the injection of a toxic
      phosphine agent. A layered intermediate compound (lead thiolate) forms in the
      initial stage of the reaction, which effectively acts as the precursor to
      decompose into the PbS nanocrystals. The size and shape of the PbS nanocrystals
      can be easily controlled by varying the reaction time, the reactant
      concentrations, the reaction temperatures, and the amount of surfactants. In
      particular, additional surfactants other than dodecanethiol, such as oleylamine,
      oleic acid, and octadecene, play an important role in the shape control of the
      products. The possible formation mechanism for the PbS nanocrystals with various
      shapes is presented on the basis of the different growth directions of the
      nanocrystals with the assistance of the different surfactants. This method
      provides a facile, low-cost, highly reproducible process for the synthesis of PbS
      nanocrystals that may have potential applications in the fabrication of
      photovoltaic devices and photodetectors.

PMID- 23126603
TI  - Sulfide catalysis without coordinatively unsaturated sites: hydrogenation, cis
      trans isomerization, and H2/D2 scrambling over MoS2 and WS2.
AB  - Simple test reactions as ethene hydrogenation, 2-butene cis-trans isomerization
      and H(2)/D(2) scrambling were shown to be catalyzed by MoS(2) and WS(2) in
      surface states which did not chemisorb oxygen and were, according to XPS
      analysis, saturated by sulfide species. This is a clear experimental disproof of
      classical concepts that require coordinative unsaturation for catalytic reactions
      to occur on such surfaces. It supports new concepts developed on model catalysts
      and by theoretical calculations so far, which have been in need of confirmation
      from real catalysis.

PMID- 23126604
TI  - Enhancement on oral absorption of paclitaxel by multifunctional pluronic
      micelles.
AB  - The aim of the present study is to synthesize Pluronic F127-polyethylenimine
      folate (PF127-PEI-FA) copolymer, construct a mixed micelle system with PF127-PEI
      FA copolymer and Pluronic P123 (PP123) and to evaluate the potential of these
      mixed micelles as an oral drug delivery system for paclitaxel (PTX). The results
      of intestinal absorption revealed that the PTX-loaded micelles displayed superior
      permeability across intestinal barrier than free drug and PF127-PEI-FA/PP123
      mixed micelles exhibited the strongest permeability across intestinal barrier.
      These results were also proved by the studies on cytotoxicity and cell uptake
      tests. The mechanism was demonstrated in connection with inhibition of the efflux
      mediated by intestinal P-glycoprotein (P-gp) and enhancement of the electrostatic
      interaction of positive micelles with the negative intestinal epithelial cells,
      thereby promoting the permeation across the intestinal wall. The presence of
      verapamil and Pluronic both improved the intestinal absorption of PTX, which
      further certified the effect of Pluronic on P-gp inhibition. Pharmacokinetic
      study demonstrated that the area under the plasma concentration-time curve (AUC(0
      >36 h)) of PTX-loaded micelles was three times greater than the PTX solution
      (dissolved in a 50/50 (vol/vol) mixture of Cremophore EL/dehydrated ethanol) (p <
      0.05). In general PF127-PEI-FA/PP123 mixed micelles were proved to be potential
      oral drug delivery system for PTX.

PMID- 23126605
TI  - Neurally adjusted ventilatory assist in weaning of neonates affected by
      congenital diaphragmatic hernia.
AB  - OBJECTIVE: The aim of the study is to evaluate the application of neurally
      adjusted ventilatory assist (NAVA) in the respiratory weaning of patients
      affected by congenital diaphragmatic hernia (CDH). METHODS: We analyzed the NAVA
      weaning in 12 neonates affected by CDH, relating the effectiveness of the
      electrical activation of the diaphragm (EAdi) signal to the type of CDH repair
      (with or without patch), the size of the patch, the stomach and His angle
      position, and the trend evaluation of some cardiorespiratory parameters with NAVA
      compared to pressure-support-ventilation (PSV). RESULTS: 5 neonates submitted to
      primary repair showed a regular EAdi signal and were successfully weaned with
      NAVA. Of the seven patients submitted to patch repair, five operated with patch
      limited to the diaphragmatic postero-lateral area had an active EAdi signal that
      permitted weaning with NAVA. Only in two neonates with hemidiaphragm agenesis was
      NAVA not feasible due to the impossibility to capture the EAdi signal. Compared
      to PSV, NAVA allows a significant improvement of oxygenation-linked indexes and
      paCO2, while PIP is reduced. CONCLUSION: Neonatal CDH with a postero-lateral
      diaphragmatic defect allows the NAVA catheter to obtain a correct EAdi signal and
      develop a viable NAVA ventilation. The lower risk of lung injury in NAVA appears
      compatible with current ventilatory strategies considered useful in CDH.

PMID- 23126606
TI  - Novel differences in the expression of inflammation-associated genes between mid-
      and late-gestational dermal fibroblasts.
AB  - While cutaneous wounds of late-gestational fetuses and on through adulthood
      result in scar formation, wounds incurred early in gestation have been shown to
      heal scarlessly. Unique properties of fetal fibroblasts are believed to mediate
      this scarless healing process. In this study, microarray analysis was used to
      identify differences in the gene expression profiles of cultured fibroblasts from
      embryonic day 15 (E15; midgestation) and embryonic day 18 (E18; late-gestation)
      skin. Sixty-two genes were differentially expressed and 12 of those genes are
      associated with inflammation, a process that correlates with scar formation in
      fetal wounds. One of the differentially expressed inflammatory genes was
      cyclooxygenase-1 (COX-1). COX-1 was more highly expressed in E18 fibroblasts than
      in E15 fibroblasts, and these differences were confirmed at the gene and protein
      level. Differences in COX-1 protein expression were also observed in fetal skin
      by immunohistochemical and immunofluorescence staining. The baseline differences
      in gene expression found in mid- and late-gestational fetal fibroblasts suggest
      that developmental alterations in fibroblasts could be involved in the transition
      from scarless to fibrotic fetal wound healing. Furthermore, baseline differences
      in the expression of inflammatory genes by fibroblasts in E15 and E18 skin may
      contribute to inflammation and scar formation late in gestation.

PMID- 23126607
TI  - Health literacy interventions and outcomes: an updated systematic review.
AB  - OBJECTIVES: To update a 2004 systematic review of health care service use and
      health outcomes related to differences in health literacy level and interventions
      designed to improve these outcomes for individuals with low health literacy.
      Disparities in health outcomes and effectiveness of interventions among different
      sociodemographic groups were also examined. DATA SOURCES: We searched MEDLINE(r),
      the Cumulative Index to Nursing and Allied Health Literature, the Cochrane
      Library, PsychINFO, and the Educational Resources Information Center. For health
      literacy, we searched using a variety of terms, limited to English and studies
      published from 2003 to May 25, 2010. For numeracy, we searched from 1966 to May
      25, 2010. REVIEW METHODS: We used standard Evidence-based Practice Center methods
      of dual review of abstracts, full-text articles, abstractions, quality ratings,
      and strength of evidence grading. We resolved disagreements by consensus.  We
      evaluated whether newer literature was available for answering key questions, so
      we broadened our definition of health literacy to include numeracy and oral
      (spoken) health literacy. We excluded intervention studies that did not measure
      health literacy directly and updated our approach to evaluate individual study
      risk of bias and to grade strength of evidence. RESULTS: We included good- and
      fair-quality studies: 81 studies addressing health outcomes (reported in 95
      articles including 86 measuring health literacy and 16 measuring numeracy, of
      which 7 measure both) and 42 studies (reported in 45 articles) addressing
      interventions.  Differences in health literacy level were consistently associated
      with increased hospitalizations, greater emergency care use, lower use of
      mammography, lower receipt of influenza vaccine, poorer ability to demonstrate
      taking medications appropriately, poorer ability to interpret labels and health
      messages, and, among seniors, poorer overall health status and higher mortality.
      Health literacy level potentially mediates disparities between blacks and whites.
      The strength of evidence of numeracy studies was insufficient to low, limiting
      conclusions about the influence of numeracy on health care service use or health
      outcomes. Two studies suggested numeracy may mediate the effect of disparities on
      health outcomes. We found no evidence concerning oral health literacy and
      outcomes.  Among intervention studies (27 randomized controlled trials [RCTs], 2
      cluster RCTs, and 13 quasi-experimental designs), the strength of evidence for
      specific design features was low or insufficient. However, several specific
      features seemed to improve comprehension in one or a few studies. The strength of
      evidence was moderate for the effect of mixed interventions on health care
      service use; the effect of intensive self-management inventions on behavior; and
      the effect of disease-management interventions on disease prevalence/severity.
      The effects of other mixed interventions on other health outcomes, including
      knowledge, self-efficacy, adherence, and quality of life, and costs were mixed;
      thus, the strength of evidence was insufficient. CONCLUSIONS: The field of health
      literacy has advanced since the 2004 report. Future research priorities include
      justifying appropriate cutoffs for health literacy levels prior to conducting
      studies; developing tools that measure additional related skills, particularly
      oral (spoken) health literacy; and examining mediators and moderators of the
      effect of health literacy. Priorities in advancing the design features of
      interventions include testing novel approaches to increase motivation, techniques
      for delivering information orally or numerically, "work around" interventions
      such as patient advocates; determining the effective components of already-tested
      interventions; determining the cost-effectiveness of programs; and determining
      the effect of policy and practice interventions.

PMID- 23126608
TI  - Temporal patterns in count-to-ten fetal movement charts and their associations
      with pregnancy characteristics: a prospective cohort study.
AB  - BACKGROUND: Fetal movement counting has long been suggested as a screening tool
      to identify impaired placental function. However, quantitative limits for
      decreased fetal movement perform poorly for screening purposes, indicating the
      need for methodological refinement. We aimed to identify the main individual
      temporal patterns in fetal movement counting charts, and explore their
      associations with pregnancy characteristics. METHODS: In a population-based
      prospective cohort in Norway, 2009-2011, women with singleton pregnancies counted
      fetal movements daily from pregnancy week 24 until delivery using a modified
      "count-to-ten" procedure. To account for intra-woman correlation of observations,
      we used functional data analysis and corresponding functional principal component
      analysis to identify the main individual temporal patterns in fetal movement
      count data. The temporal patterns are described by continuous functional
      principal component (FPC) curves, with an individual score on each FPC for each
      woman. These scores were later used as outcome variables in multivariable linear
      regression analyses, with pregnancy characteristics as explanatory variables.
      RESULTS: Fetal movement charts from 1086 pregnancies were included. Three FPC
      curves explained almost 99% of the variation in the temporal data, with the first
      FPC, representing the individual overall counting time, accounting for 91% alone.
      There were several statistically significant associations between the FPCs and
      various pregnancy characteristics. However, the effects were small and of limited
      clinical value. CONCLUSIONS: This statistical approach for analyzing fetal
      movement counting data successfully captured clinically meaningful individual
      temporal patterns and how these patterns vary between women. Maternal body mass
      index, gestational age and placental site explained little of the variation in
      the temporal fetal movement counting patterns. Thus, a perceived decrease in
      fetal movement should not be attributed to a woman's basic pregnancy
      characteristics, but assessed as a potential marker of risk.

PMID- 23126609
TI  - Effect of butorphanol on thermal nociceptive threshold in healthy pony foals.
AB  - REASONS FOR PERFORMING STUDY: Pain management is an important component of foal
      nursing care, and no objective data currently exist regarding the analgesic
      efficacy of opioids in foals. OBJECTIVES: To evaluate the somatic antinociceptive
      effects of 2 commonly used doses of intravenous (i.v.) butorphanol in healthy
      foals. Our hypothesis was that thermal nociceptive threshold would increase
      following i.v. butorphanol in a dose-dependent manner in both neonatal and older
      pony foals. METHODS: Seven healthy neonatal pony foals (age 1-2 weeks), and 11
      healthy older pony foals (age 4-8 weeks). Five foals were used during both age
      periods. Treatments, which included saline (0.5 ml), butorphanol (0.05 mg/kg bwt)
      and butorphanol (0.1 mg/kg bwt), were administered i.v. in a randomised crossover
      design with at least 2 days between treatments. Response variables included
      thermal nociceptive threshold, skin temperature and behaviour score. Data within
      each age period were analysed using a 2-way repeated measures ANOVA, followed by
      a Holm-Sidak multiple comparison procedure if warranted. RESULTS: There was a
      significant (P<0.05) increase in thermal threshold, relative to Time 0, following
      butorphanol (0.1 mg/kg bwt) administration in both age groups. No significant
      time or treatment effects were apparent for skin temperature. Significant time,
      but not treatment, effects were evident for behaviour score in both age groups.
      CONCLUSIONS: Butorphanol (0.1 mg/kg bwt, but not 0.05 mg/kg bwt) significantly
      increased thermal nociceptive threshold in neonatal and older foals without
      apparent adverse behavioural effects. POTENTIAL RELEVANCE: Butorphanol shows
      analgesic potential in foals for management of somatic painful conditions.

PMID- 23126610
TI  - Composition of the essential oil of Buddleja thyrsoides Lam. leaves from Brazil.
AB  - This study is designed to examine the chemical composition of the essential oil
      obtained from Buddleja thyrsoides Lam leaves from south Brazil. Gas
      chromatography/mass spectrometry analysis resulted in the detection of 12
      components, representing 91.4% of the total oil composition. Germacrene D
      (27.16%), 1,10-di-epi-Cubenol (13.37%), alpha-Cadinol (12.95%), Bicyclogermacrene
      (9.00%), Globulol (8.59%) and caryophylene E (5.26%) were the main components. To
      the best of our knowledge, this is the first study of the composition of
      essential oil of the B. thyrsoides collected in Brazil. 

PMID- 23126611
TI  - Groupwise information sharing promotes ingroup favoritism in indirect
      reciprocity.
AB  - BACKGROUND: Indirect reciprocity is a mechanism for cooperation in social dilemma
      situations. In indirect reciprocity, an individual is motivated to help another
      to acquire a good reputation and receive help from others afterwards. Another
      aspect of human cooperation is ingroup favoritism, whereby individuals help
      members in their own group more often than those in other groups. Ingroup
      favoritism is a puzzle for the theory of cooperation because it is not easily
      evolutionarily stable. In the context of indirect reciprocity, ingroup favoritism
      has been shown to be a consequence of employing a double standard when assigning
      reputations to ingroup and outgroup members. An example of such a double standard
      is the situation in which helping an ingroup member is regarded as good, whereas
      the same action toward an outgroup member is regarded as bad. RESULTS: We analyze
      a computational model of indirect reciprocity in which information sharing is
      conducted groupwise. In our model, individuals play social dilemma games within
      and across groups, and the information about their reputations is shared within
      each group. We show that evolutionarily stable ingroup favoritism emerges even if
      all the players use the same reputation assignment rule regardless of group
      (i.e., a single standard). Two reputation assignment rules called simple standing
      and stern judging yield ingroup favoritism; under these rules, cooperation with
      (defection against) good individuals is regarded as good (bad) and defection
      against bad individuals is regarded as good. Stern judging induces much stronger
      ingroup favoritism than does simple standing. Simple standing and stern judging
      are evolutionarily stable against each other when groups employing different
      assignment rules compete and the number of groups is sufficiently large. In
      addition, we analytically show as a limiting case that homogeneous populations of
      reciprocators that use reputations are unstable when individuals independently
      infer reputations of individuals, which is consistent with previously reported
      numerical results. CONCLUSIONS: Our results suggest that ingroup favoritism can
      be promoted in indirect reciprocity by the groupwise information sharing, in
      particular under the stern judging assignment rule.

PMID- 23126612
TI  - Bioenergy production from perennial energy crops: a consequential LCA of 12
      bioenergy scenarios including land use changes.
AB  - In the endeavor of optimizing the sustainability of bioenergy production in
      Denmark, this consequential life cycle assessment (LCA) evaluated the
      environmental impacts associated with the production of heat and electricity from
      one hectare of Danish arable land cultivated with three perennial crops: ryegrass
      (Lolium perenne), willow (Salix viminalis) and Miscanthus giganteus. For each,
      four conversion pathways were assessed against a fossil fuel reference: (I)
      anaerobic co-digestion with manure, (II) gasification, (III) combustion in small
      to-medium scale biomass combined heat and power (CHP) plants and IV) co-firing in
      large scale coal-fired CHP plants. Soil carbon changes, direct and indirect land
      use changes as well as uncertainty analysis (sensitivity, MonteCarlo) were
      included in the LCA. Results showed that global warming was the bottleneck
      impact, where only two scenarios, namely willow and Miscanthus co-firing, allowed
      for an improvement as compared with the reference (-82 and -45 t CO2-eq. ha-1,
      respectively). The indirect land use changes impact was quantified as 310 +/- 170
      t CO2-eq. ha-1, representing a paramount average of 41% of the induced greenhouse
      gas emissions. The uncertainty analysis confirmed the results robustness and
      highlighted the indirect land use changes uncertainty as the only uncertainty
      that can significantly change the outcome of the LCA results.

PMID- 23126613
TI  - Application of hyperdry amniotic membrane patches without fibrin glue over the
      bony surface of mastoid cavities in canal wall down tympanoplasty.
AB  - CONCLUSION: Fibrin glue might be an inessential bioadhesive for attachment of
      hyperdry amniotic membrane (AM) patches in canal wall down (CWD) tympanoplasty.
      OBJECTIVE: To clarify the pliability and adherence capability of human hyperdry
      AM, the feasibility of fixing hyperdry AM without fibrin glue to the bony surface
      of the mastoid cavity was evaluated in CWD tympanoplasty. METHODS: This was a
      retrospective chart review. In seven ears of seven patients, the AM was simply
      attached over the bony surface of the mastoid cavity without fibrin glue (AMG(-)
      group). In 22 ears of 20 other patients, hyperdry AM (11 ears of 11 patients,
      AMG(+) group) or temporal fascia (11 ears of 9 patients, TFG(+) group) was
      attached over the bony surface of the mastoid cavity with fibrin glue. Times for
      graft epithelization were compared among the three groups. RESULTS: Complete
      epithelization of the mastoid cavity took place in all patients in all three
      groups. The mean time to complete epithelization of the graft in the AMG(-) and
      AMG(+) groups was significantly faster than that in the TFG(+) group (p < 0.05)
      and was not significantly different between the two AM groups (p > 0.05).

PMID- 23126614
TI  - Calcaneal spur in an 18-month-old boy.

PMID- 23126615
TI  - Spatial epidemiology of eastern equine encephalitis in Florida.
AB  - BACKGROUND: Eastern Equine Encephalitis virus (EEEV) is an alphavirus with high
      pathogenicity in both humans and horses. Florida continues to have the highest
      occurrence of human cases in the USA, with four fatalities recorded in 2010.
      Unlike other states, Florida supports year-round EEEV transmission. This research
      uses GIS to examine spatial patterns of documented horse cases during 2005-2010
      in order to understand the relationships between habitat and transmission
      intensity of EEEV in Florida. METHODS: Cumulative incidence rates of EEE in
      horses were calculated for each county. Two cluster analyses were performed using
      density-based spatial clustering of applications with noise (DBSCAN). The first
      analysis was based on regional clustering while the second focused on local
      clustering. Ecological associations of EEEV were examined using compositional
      analysis and Euclidean distance analysis to determine if the proportion or
      proximity of certain habitats played a role in transmission. RESULTS: The DBSCAN
      algorithm identified five distinct regional spatial clusters that contained 360
      of the 438 horse cases. The local clustering resulted in 18 separate clusters
      containing 105 of the 438 cases. Both the compositional analysis and Euclidean
      distance analysis indicated that the top five habitats positively associated with
      horse cases were rural residential areas, crop and pastureland, upland hardwood
      forests, vegetated non-forested wetlands, and tree plantations. CONCLUSIONS: This
      study demonstrates that in Florida tree plantations are a focus for epizootic
      transmission of EEEV. It appears both the abundance and proximity of tree
      plantations are factors associated with increased risk of EEE in horses and
      therefore humans. This association helps to explain why there is are spatially
      distinct differences in the amount of EEE horse cases across Florida.

PMID- 23126616
TI  - Preservation of hepatocyte nuclear factor-4alpha contributes to the beneficial
      effect of dietary medium chain triglyceride on alcohol-induced hepatic lipid
      dyshomeostasis in rats.
AB  - BACKGROUND: Alcohol consumption is a major cause of fatty liver, and dietary
      saturated fats have been shown to protect against alcoholic fatty liver. This
      study investigated the mechanisms of how dietary saturated fat may modulate
      alcohol-induced hepatic lipid dyshomeostasis. METHODS: Male Sprague Dawley rats
      were pair-fed with 3 isocaloric liquid diets, control, alcohol, and medium chain
      triglyceride (MCT)/alcohol, respectively, for 8 weeks. The control and alcohol
      diets were based on the Lieber-DeCarli liquid diet formula with 30% total
      calories derived from corn oil (rich in unsaturated long chain fatty acids). The
      corn oil was replaced by MCT, which consists of exclusive saturated fatty acids,
      in the MCT/alcohol diet. HepG2 cell culture was conducted to test the effects of
      unsaturated fatty acids on hepatocyte nuclear factor-4alpha (HNF4alpha) and the
      role of HNF4alpha in regulating hepatocyte lipid homeostasis. RESULTS: Alcohol
      feeding caused significant lipid accumulation, which was attenuated by dietary
      MCT. The major effect of alcohol on hepatic gene expression is the up-regulation
      of CYP4A1, CD36, and GPAT3, and down-regulation of apolipoprotein B (ApoB).
      Dietary MCT further up-regulated CYP4A1 gene, normalized ApoB gene, and up
      regulated MTTP and SCD1 genes. The protein level of HNF4alpha, a master
      transcription factor of the liver, was reduced by alcohol feeding, which was
      normalized by dietary MCT. Fatty acid profiling demonstrated that alcohol feeding
      dramatically increased hepatic unsaturated long chain fatty acyl species,
      particularly linoleic acid and oleic acid, which was attenuated by dietary MCT.
      Dietary MCT attenuated alcohol-reduced serum triglyceride level and modulated the
      fatty acid composition of the serum triglycerides. Cell culture study
      demonstrated polyunsaturated linoleic acid rather than monounsaturated oleic acid
      inactivated HNF4alpha in HepG2 cells. Knockdown of HNF4alpha caused lipid
      accumulation in HepG2 cells due to dysregulation of very low density lipoprotein
      secretion. CONCLUSIONS: Results suggest that dietary MCT prevents alcohol-induced
      hepatic lipid accumulation, at least partially, through reducing hepatic
      polyunsaturated long chain fatty acids and preserving HNF4alpha.

PMID- 23126617
TI  - Pathophysiology of urinary incontinence in murine models.
AB  - Urethral closure mechanisms under stress conditions consist of passive urethral
      closure involving connective tissues, fascia and/or ligaments in the pelvis and
      active urethral closure mediated by hypogastric, pelvic and pudendal nerves.
      Furthermore, we have previously reported that the active urethral closure
      mechanism might be divided into two categories: (i) the central nervous control
      passing onto Onuf's nucleus under sneezing or coughing; and (ii) the bladder-to
      urethral spinal reflex under Valsalva-like stress conditions, such as laughing,
      exercise or lifting heavy objects. There are over 200 million people worldwide
      with urinary incontinence, a condition that is associated with a significant
      social impact and reduced quality of life. Therefore, basic research for urinary
      continence mechanisms in response to different stress conditions can play an
      essential role in developing treatments for stress urinary incontinence. It has
      been clinically shown that the etiology of stress urinary incontinence is divided
      into urethral hypermobility and intrinsic sphincter deficiency, which could
      respectively correspond to passive and active urethral closure dysfunction. In
      this review, we summarize the representative stress urinary incontinence animal
      models and the methods to measure leak point pressures under stress conditions,
      and then highlight stress-induced urinary continence mechanisms mediated by
      active urethral closure mechanisms, as well as future pharmacological treatments
      of stress urinary incontinence. In addition, we introduce our previous reports
      including sex differences in urethral closure mechanisms under stress conditions
      and urethral compensatory mechanisms to maintain urinary continence after
      pudendal nerve injury in female rats.

PMID- 23126619
TI  - Balancing reactive oxygen species in the epigenome: NADPH oxidases as target and
      perpetrator.
AB  - SIGNIFICANCE: NADPH oxidases are important sources for regulated generation of
      reactive oxygen species (ROS). The main ROS produced are superoxide and hydrogen
      peroxide, both of which are redox signaling molecules in the context of various
      cellular functions. Redox imbalance due to excessive or insufficient ROS is a
      hallmark of pathophysiological aspects, including cancer development and
      progression. RECENT ADVANCES: Epigenetic silencing of NADPH oxidases by
      hypermethylation of their promoter region or of the genes required for their
      assembly and activity occurs in diseases, such as lung cancer, and may represent
      an early stage of neoplastic transformation. CRITICAL ISSUES: Loss of ROS
      mediated signaling by epigenetic silencing may promote tumorigenesis. Conversely,
      increased oxidative stress caused by oncogene-induced overexpression of NADPH
      oxidases may also drive epigenetic instability. Thus, the cellular redox balance
      is likely vital in carcinogenesis. FUTURE DIRECTIONS: NADPH oxidases may serve as
      prognostic tumor biomarker, especially when their individual expression is
      confined to accessible tissues, such as mucosal epithelia or blood. Further
      validation of NADPH oxidase/dual oxidase enzymes as candidate markers will
      require well controlled, large-scale clinical data sets. This review is focused
      on NADPH oxidases as targets of epigenetic changes in cancer and on the emerging
      role of ROS as inducers of epigenetic changes.

PMID- 23126620
TI  - Organocatalytic carbonyl-olefin metathesis.
AB  - The development of a catalytic carbonyl-olefin metathesis strategy is reported,
      in the context of the ring-opening metathesis of cyclopropenes with aldehydes
      using a simple hydrazine catalyst. The key to this reaction is a conceptual
      blueprint for metathesis chemistry that forgoes the traditional reliance on [2 +
      2] cycloaddition modes in favor of a [3 + 2] paradigm.

PMID- 23126622
TI  - Disruptions in the supply of medications used in transplantation: implications
      and management strategies for the transplant clinician.
AB  - Drug shortages are a threat to patient care and public health, and the number of
      drugs on shortage is growing at an exponential rate. The major therapy areas
      affected by these shortages are oncology, anti-infective, cardiovascular and
      central nervous system. However, drugs utilized in the transplant patient
      population have not been exempt, and can have significant influence on
      posttransplant outcomes. The purpose of this review is to discuss the current and
      historical solid organ transplant-related disruptions in the supply of
      medications and implications on patient care and safety. Transplant centers
      should be armed with an implementation plan when imperative transplant-related
      drugs such as tacrolimus, mycophenolate, or antithymocyte globulin go on
      shortage. This plan should provide steps to manage the shortage, and provide
      effective therapeutic alternatives.

PMID- 23126621
TI  - Mutations in the SLAC1 anion channel slow stomatal opening and severely reduce K+
      uptake channel activity via enhanced cytosolic [Ca2+] and increased Ca2+
      sensitivity of K+ uptake channels.
AB  - The Arabidopsis guard cell anion channel SLAC1 is essential for stomatal closure
      in response to various endogenous and environmental stimuli. Interestingly, here
      we reveal an unexpected impairment of slac1 alleles on stomatal opening. We
      report that mutations in SLAC1 unexpectedly slow stomatal opening induced by
      light, low CO(2) and elevated air humidity in intact plants and that this is
      caused by the severely reduced activity of inward K(+) (K(+)(in)) channels in
      slac1 guard cells. Expression of channels and transporters involved in stomatal
      opening showed small but significant reductions in transcript levels in slac1
      guard cells; however, this was deemed insufficient to explain the severely
      impaired K(+)(in) channel activity in slac1. We further examined resting
      cytosolic Ca(2+) concentration ([Ca(2+)](cyt)) and K(+)(in) channel sensitivity
      to [Ca(2+)](cyt) in slac1. These experiments showed higher resting [Ca(2+)](cyt)
      in slac1 guard cells and that reducing [Ca(2+)](cyt) to < 10 nM rapidly restored
      the activity of K(+)(in) channels in slac1 closer to wild-type levels. These
      findings demonstrate an unanticipated compensatory feedback control in plant
      stomatal regulation, which counteracts the impaired stomatal closing response of
      slac1, by down-regulating stomatal opening mechanisms and implicates enhanced
      [Ca(2+)](cyt) sensitivity priming as a mechanistic basis for the down-regulated
      K(+)(in) channel activity.

PMID- 23126623
TI  - Volatiles profiling in medicinal licorice roots using steam distillation and
      solid-phase microextraction (SPME) coupled to chemometrics.
AB  - Licorice (Glycyrrhiza glabra L.) is a plant of considerable commercial importance
      in traditional medicine and for the flavor and sweets industry. Although
      Glycyrrhiza species are very competitive targets for phytochemical studies, very
      little is known about the volatiles composition within that genus, although such
      knowledge can be suspected to be relevant for understanding the olfactory and
      taste properties. To provide insight into Glycyrrhiza species aroma composition
      and for its use in food and pharmaceutical industry, volatile constituents from
      G. glabra, G. inflata, and G. echinata roots were profiled using steam
      distillation and solid-phase microextraction. Two phenols, thymol and carvacrol,
      were found exclusively in essential oil and headspace samples of G. glabra, and
      with highest amounts for samples that originated from Egypt. In G. echinata oil,
      (2E, 4E)-decadienal (21%) and beta-caryophyllene oxide (24%) were found as main
      constituents, whereas 1alpha, 10alpha-epoxyamorpha-4-ene (13%) and beta
      dihydroionone (8%) predominated G. inflata. Principal component and hierarchical
      cluster analyses clearly separated G. echinata and G. inflata from G. glabra;
      with phenolics and aliphatic aldehydes contributing mostly for species
      segregation. PRACTICAL APPLICATION: Licorice (Glycyrrhiza glabra) has large
      economic, nutritional, and medicinal values. The data presented in this article
      help in licorice quality control analysis to identify G. glabra from its closely
      allied species. The presence of thymol and carvacrol exclusively in G. glabra
      suggests that these volatiles could serve as chemotaxonomic markers and also
      might be considered as potentially relevant for taste.

PMID- 23126624
TI  - Management of persistent pain in older adults: the MOBILIZE Boston Study.
AB  - OBJECTIVES: To describe the prevalence of pharmacological (PS) and
      nonpharmacological (NPS) pain management approaches used by older adults with
      persistent pain and to identify characteristics associated with use of these
      approaches. DESIGN: Population-based cohort. SETTING: Urban and suburban
      communities in the Boston, Massachusetts, area. PARTICIPANTS: Seven hundred sixty
      five adults aged 64 and older underwent a home interview and clinic examination.
      Those reporting any persistent pain were included in this analysis (N = 599).
      MEASUREMENTS: All prescription and nonprescription medications were recorded
      during the home interview. NPS modalities for pain management were assessed using
      a modification of the Pain Management Inventory. The baseline assessment included
      extensive measures of pain, health, and functioning. RESULTS: More than one-third
      (37.5%) of participants reported using both PS and NPS modalities. Thirty-one
      percent reported use of NPS modalities alone, and 11.5% used PS modalities alone.
      NPS modalities (68.4%) were reported more frequently than PS modalities (49%).
      Women (odds ratio (OR)= 2.2, 95% confidence interval (CI) = 1.26-3.82),
      individuals with knee osteoarthritis (OR = 3.07, 95% CI = 1.6-5.9), and
      individuals with moderate to severe pain (OR = 5.02, 95% CI = 2.23-11.28) were
      more likely to report combined use of PS and NPS modalities. Characteristics
      associated with individual NPS modalities varied greatly. CONCLUSION: Only one
      third of older adults with persistent pain reported pain management strategies
      consistent with current guidelines. Further research is required to understand
      reasons behind choices, barriers to adherence, and the benefits of multiple
      modalities that older adults with persistent pain use.

PMID- 23126625
TI  - Quinolinic alkaloids from Galipea longiflora Krause suppress production of
      proinflammatory cytokines in vitro and control inflammation in vivo upon
      Leishmania infection in mice.
AB  - An antileishmanial activity of quinolinic alkaloids from Galipea longiflora
      Krause, known as Evanta, has been demonstrated. We have previously shown that,
      apart from its leishmanicidal effect, in vitro pretreatment of spleen cells with
      an alkaloid extract of Evanta (AEE) interfered with the proliferation and
      interferon-gamma production in lymphocytes polyclonally activated either with
      concanavalin A or anti-CD3. In the present study, we investigated if AEE could
      interfere with antigen-specific lymphocyte activation. We found that in vitro and
      in vivo treatment reduced recall lymphocyte responses, as measured by IFN-gamma
      production (55% and 63% reduction compared to untreated cells, respectively).
      Apart from IFN-gamma, the production of IL-12 and TNF was also suppressed. No
      effects were observed for meglumine antimoniate (SbV), the conventional drug used
      to treat leishmaniasis. When mice infected with Leishmania braziliensis
      promastigotes in the hind footpad were treated with AEE, the dynamics of the
      infection changed and the footpath thickness was efficiently controlled. The
      parasite load was also reduced but to a lesser extent than upon treatment with
      SbV. Combined treatment efficiently controlled both the thickness and parasite
      load as smaller lesions during the entire course of the infection were seen in
      the mice treated with AEE plus SbV compared with AEE or SbV alone. We discuss the
      benefits of combined administration of AEE plus SbV.

PMID- 23126626
TI  - Core refinement toward permeable beta-secretase (BACE-1) inhibitors with low hERG
      activity.
AB  - By use of iterative design aided by predictive models for target affinity, brain
      permeability, and hERG activity, novel and diverse compounds based on cyclic
      amidine and guanidine cores were synthesized with the goal of finding BACE-1
      inhibitors as a treatment for Alzheimer's disease. Since synthesis feasibility
      had low priority in the design of the cores, an extensive synthesis effort was
      needed to make the relevant compounds. Syntheses of these compounds are reported,
      together with physicochemical properties and structure-activity relationships
      based on in vitro data. Four crystal structures of diverse amidines binding in
      the active site are deposited and discussed. Inhibitors of BACE-1 with 3 MUM to
      32 nM potencies in cells are shown, together with data on in vivo brain exposure
      levels for four compounds. The results presented show the importance of the core
      structure for the profile of the final compounds.

PMID- 23126627
TI  - Safety of probiotics used to reduce risk and prevent or treat disease.
AB  - OBJECTIVES: To catalog what is known about the safety of interventions containing
      Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus,
      and/or Bacillus strains used as probiotic agents in research to reduce the risk
      of, prevent, or treat disease. DATA SOURCES: We searched 12 electronic databases,
      references of included studies, and pertinent reviews for studies addressing the
      safety of probiotics from database inception to August 2010 without language
      restriction. REVIEW METHODS: We identified intervention studies on probiotics
      that reported the presence or absence of adverse health outcomes in human
      participants, without restriction by study design, participant type, or clinical
      field. We investigated the quantity, quality, and nature of adverse events.
      RESULTS: The search identified 11,977 publications, of which 622 studies were
      included in the review. In 235 studies, only nonspecific safety statements were
      made ("well tolerated"); the remaining 387 studies reported the presence or
      absence of specific adverse events. Interventions and adverse events were poorly
      documented.  A number of case studies described fungemia and some bacteremia
      potentially associated with administered probiotic organisms. Controlled trials
      did not monitor routinely for such infections and primarily reported on
      gastrointestinal adverse events. Based on reported adverse events, randomized
      controlled trials (RCTs) showed no statistically significantly increased relative
      risk (RR) of the overall number of experienced adverse events (RR 1.00; 95%
      confidence interval [CI]: 0.93, 1.07, p=0.999); gastrointestinal; infections; or
      other adverse events, including serious adverse events (RR 1.06; 95% CI: 0.97,
      1.16; p=0.201), associated with short-term probiotic use compared to control
      group participants; long-term effects are largely unknown. Existing studies
      primarily examined Lactobacillus alone or in combination with other genera, often
      Bifidobacterium.  Few studies directly compared the safety among different
      intervention or participant characteristics. Indirect comparisons indicated that
      effects of delivery vehicles (e.g., yogurt, dairy) should be investigated
      further. Case studies suggested that participants with compromised health are
      most likely to experience adverse events associated with probiotics. However,
      RCTs in medium-risk and critically ill participants did not report a
      statistically significantly increased risk of adverse events compared to control
      group participants. CONCLUSIONS: There is a lack of assessment and systematic
      reporting of adverse events in probiotic intervention studies, and interventions
      are poorly documented. The available evidence in RCTs does not indicate an
      increased risk; however, rare adverse events are difficult to assess, and despite
      the substantial number of publications, the current literature is not well
      equipped to answer questions on the safety of probiotic interventions with
      confidence.

PMID- 23126628
TI  - Traditional, complementary and alternative medical systems and their contribution
      to personalisation, prediction and prevention in medicine-person-centred
      medicine.
AB  - Traditional, complementary and alternative medical (TCAM) systems contribute to
      the foundation of person-centred medicine (PCM), an epistemological orientation
      for medical science which places the person as a physical, psychological and
      spiritual entity at the centre of health care and of the therapeutic process. PCM
      wishes to broaden the bio-molecular reductionistic approach of medical science
      towards an integration that allows people, doctors, nurses, health-care
      professionals and patients to become the real protagonists of the health-care
      scene. The doctor or caregiver needs to act out of empathy to meet the unique
      value of each human being, which unfolds over the course of a lifetime from
      conception to natural death. Knowledge of the human being should not be
      instrumental to economic or political interests, ideology, theories or religious
      dogma. Research needs to be broadened with methodological tools to investigate
      person-centred medical interventions. Salutogenesis is a fundamental principle of
      PCM, promoting health and preventing illness by strengthening the individual's
      self-healing abilities. TCAM systems also give tools to predict the insurgence of
      illness and treat it before the appearance of overt organic disease. A task of
      PCM is to educate people to take better care of their physical, psychological and
      spiritual health. Health-care education needs to be broadened to give doctors and
      health-care workers of the future the tools to act in innovative and highly
      differentiated ways, always guided by deep respect for individual autonomy,
      personal culture, religion and beliefs.

PMID- 23126629
TI  - Long PCR-RFLP of 16S-ITS-23S rRNA genes: a high-resolution molecular tool for
      bacterial genotyping.
AB  - AIMS: To perform a systematic evaluation of the applicability, validity and
      reliability of the long PCR-RFLP of 16S-ITS-23S rRNA genes for bacterial
      genotyping using both sequences retrieved from public genome databases and the
      experimental data obtained on bacterial cultures. METHODS AND RESULTS: 3301 Full
      length sequences of 16S-ITS-23S rRNA genes were retrieved from 885 published
      bacterial genomes. Copy numbers of the whole set of 16S-ITS-23S rRNA genes per
      genome ranged from 1 (n = 161) to 14 (n = 4) with an average of 3.71. Their
      length varied greatly, from 4319 to 6568 bp with an average of 4952 bp. Computer
      simulated RFLP analyses of the 16S-ITS-23S fragments flanked by the conserved
      primers 27F and 2241R suggested MspI, RsaI, HhaI and TaqI as the most appropriate
      enzymes for long PCR-RFLP analysis of the 16S-ITS-23S sequence. MspI was used to
      screen over 900 bacterial cultures isolated from the Huguangyan Maar Lake in
      southern China. An experimental sequencing of 16S rRNA genes of the isolates
      possessing a unique RFLP band pattern proved the broad applicability and high
      resolution of this approach. CONCLUSIONS: These results indicate that long PCR
      RFLP of 16S-ITS-23S rRNA genes is a potentially universal and reliable bacterial
      genotyping tool with a high resolution. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      methodology of long PCR-RFLP of 16S-ITS-23S rRNA genes will facilitate the
      exploration and tracing of cultivable microbial diversity in natural
      environments.

PMID- 23126630
TI  - Near- and supercritical alcohols as solvents and surface modifiers for the
      continuous synthesis of cerium oxide nanoparticles.
AB  - Supercritical fluids offer fast and facile routes toward well-crystallized tailor
      made cerium oxide nanoparticles. However, the use of surfactants to control
      morphology and surface properties remains essential. Therefore, although water,
      near-critical (nc) or supercritical (sc), is a solvent of choice, the poor water
      solubility of some surfactants could require other solvent systems such as
      alcohols, which could themselves behave as surface modifiers. In here, the
      influence of seven different alcohols, MeOH, EtOH, PrOH, iPrOH, ButOH, PentOH,
      and HexOH, in alcothermal conditions (300  degrees C, 24.5 MPa) over CeO(2)
      nanocrystals (NCs) size, morphology, and surface properties was investigated. The
      crystallite size of the CeO(2) nanocrystals can be tuned in the range 3-7 nm
      depending on the considered alcohol, and their surface has been modified by these
      solvents without the use of surfactants. Mechanisms are proposed for the
      interaction of primary and secondary alcohols with CeO(2) surface and its
      functionalization during the synthesis based on FTIR and TGA-MS studies. This
      study allows apprehending the role of alcohols during the synthesis and may lead
      to an informed choice of solvent as a function of the required size and surface
      properties of CeO(2) NCs. It also opens new route to CeO(2) functionalization
      using supercritical alcohol derivatives.

PMID- 23126631
TI  - Alipogene tiparvovec: gene therapy for lipoprotein lipase deficiency.
AB  - Homozygous lipoprotein lipase (LPL) deficiency is an ultra-orphan disease
      associated with increased rates of pancreatitis. Current treatments based on
      acute plasmapheresis allied with ultra-low fat diets are inadequate as responses
      to fibrates or other triglyceride-lowering therapies tend to be poor. Alipogene
      tiparvovec is an adeno-associated virus type I (AAV1) gene therapy using a hyper
      functional LPL serine(447)-stop (S447X) insert administered intramuscularly under
      general anaesthetic with allied immunosuppression. Treatment results in
      histological muscle expression of LPL allied with a transient 40% reduction in
      triglycerides and improvements in postprandial chylomicron triglyceride content.
      Alipogene tiparvovec is the first possibly curative treatment for LPL deficiency.

PMID- 23126632
TI  - Nanofibrous structured biomimetic strategies for skin tissue regeneration.
AB  - Mimicking porous topography of natural extracellular matrix is advantageous for
      successful regeneration of damaged tissues or organs. Nanotechnology being one of
      the most promising and growing technology today shows an extremely huge potential
      in the field of tissue engineering. Nanofibrous structures that mimic the native
      extracellular matrix and promote the adhesion of various cells are being
      developed as tissue-engineered scaffolds for skin, bone, vasculature, heart,
      cornea, nervous system, and other tissues. A range of novel biocomposite
      materials has been developed to enhance the bioactive or therapeutic properties
      of these nanofibrous scaffolds via surface modifications, including the
      immobilization of functional cell-adhesive ligands and bioactive molecules such
      as drugs, enzymes, and cytokines. In skin tissue engineering, usage of allogeneic
      skin is avoided to reestablish physiological continuity and also to address the
      challenge of curing acute and chronic wounds, which remains as the area of
      exploration with various biomimetic approaches. Two-dimensional, three
      dimensional scaffolds and stem cells are presently used as dermal regeneration
      templates for the treatment of full-thickness skin defects resulting from
      injuries and severe burns. The present review elaborates specifically on the
      fabrication of nanofibrous structured strategies for wound dressings, wound
      healing, and controlled release of growth factors for skin tissue regeneration.

PMID- 23126633
TI  - Delays in the delivery room of a primary maternity unit: a retrospective analysis
      of obstetric outcomes.
AB  - OBJECTIVE: To compare obstetric outcomes in women undergoing vaginal delivery
      with or without delay in the 2nd and 3rd stage of labour (SOL). METHODS: This is
      an observational retrospective study including 10,416 full-term vaginal
      deliveries occurred at a primary obstetric unit. Our sample was divided according
      to the length of 2nd and 3rd SOL: >2 h vs. <=2 h; and >1 h vs. <=1 h,
      respectively. Obstetric outcomes were compared using univariate and multivariate
      analysis. RESULTS: A prolonged 2nd SOL was associated with severe perineal tears
      (odds ratio (OR) = 3.53), episiotomy (OR = 3.25), major post-partum hemorrhage
      (PPH) (OR = 2.35), operative delivery (OR = 3.54), and Asian ethnicity (OR =
      12.12). Likewise, a prolonged 3rd SOL was associated with operative deliveries
      (OR = 10.49), labor induction (OR = 3.24), non-use of oxytocin after delivery (OR
      = 12.39), major PPH (OR = 46.95), retained placenta (OR = 3.57) and female fetal
      gender (OR = 4.07). CONCLUSIONS: even at a primary care setting, where there are
      mostly low-risk pregnancies, a prolonged 2nd and 3rd SOL may occur and lead to
      poor obstetric outcomes. Our findings raise a very controversial issue about the
      meaning of "low obstetrics risk", given the unpredictability of any labor, and
      the management of complications in the delivery room of primary maternity units.

PMID- 23126634
TI  - Electrophilic alpha-amination reaction of beta-ketoesters using N
      hydroxycarbamates: merging aerobic oxidation and Lewis acid catalysis.
AB  - The copper-catalyzed alpha-amination of carbonyl compounds using nitrosoformate
      intermediates as the electrophilic source of nitrogen is reported. The reaction
      merges aerobic oxidation and Lewis acid catalysis. The scope of the reaction is
      broad in terms of both the N-substituted hydroxylamines and the beta-ketoesters.
      The new methodology harnesses the power of nitrosoformate intermediates and
      demonstrates their potential as a viable electrophilic source of nitrogen in
      alpha-functionalization reactions.

PMID- 23126635
TI  - New 2,2-diphenylpropane and ethoxylated aromatic monoterpenes from Lavandula
      gibsoni (Lamiaceae).
AB  - A new substituted 2,2-diphenylpropane (1) and two new ethoxylated aromatic
      monoterpene alcohols (2 and 4) have been isolated from the acetone extract of the
      aerial parts of Lavandula gibsoni, along with the known compounds 8
      hydroxycarvacrol (3), 8-hydroxythymol (5), coumarin (6), 4-methylresorcinol (7),
      7,4'-dimethylapigenin (8), salvigenin (9), beta-sitosteryl-3-O-beta-D
      glucopyranosyl-6'-O-palmitate (10) and euscaphic acid D (11). The structures of
      the isolated compounds were assigned on the basis of their (1)H- and (13)C-NMR
      spectra and two-dimensional NMR techniques, which included COSY, HSQC, HMBC and
      NOESY experiments and comparison with the reported literature.

PMID- 23126636
TI  - Response to Hex et al. Estimating the current and future costs of Type 1 and Type
      2 diabetes in the UK, including direct health costs and indirect societal and
      productivity costs.

PMID- 23126637
TI  - Resolving candidate genes of mouse skeletal muscle QTL via RNA-Seq and expression
      network analyses.
AB  - BACKGROUND: We have recently identified a number of Quantitative Trait Loci (QTL)
      contributing to the 2-fold muscle weight difference between the LG/J and SM/J
      mouse strains and refined their confidence intervals. To facilitate nomination of
      the candidate genes responsible for these differences we examined the
      transcriptome of the tibialis anterior (TA) muscle of each strain by RNA-Seq.
      RESULTS: 13,726 genes were expressed in mouse skeletal muscle. Intersection of a
      set of 1061 differentially expressed transcripts with a mouse muscle Bayesian
      Network identified a coherent set of differentially expressed genes that we term
      the LG/J and SM/J Regulatory Network (LSRN). The integration of the QTL,
      transcriptome and the network analyses identified eight key drivers of the LSRN
      (Kdr, Plbd1, Mgp, Fah, Prss23, 2310014F06Rik, Grtp1, Stk10) residing within five
      QTL regions, which were either polymorphic or differentially expressed between
      the two strains and are strong candidates for quantitative trait genes (QTGs)
      underlying muscle mass. The insight gained from network analysis including the
      ability to make testable predictions is illustrated by annotating the LSRN with
      knowledge-based signatures and showing that the SM/J state of the network
      corresponds to a more oxidative state. We validated this prediction by NADH
      tetrazolium reductase staining in the TA muscle revealing higher oxidative
      potential of the SM/J compared to the LG/J strain (p<0.03). CONCLUSION: Thus,
      integration of fine resolution QTL mapping, RNA-Seq transcriptome information and
      mouse muscle Bayesian Network analysis provides a novel and unbiased strategy for
      nomination of muscle QTGs.

PMID- 23126638
TI  - Gene expression patterns and life cycle responses of toxicant-exposed
      chironomids.
AB  - Cellular stress responses are frequently presumed to be more sensitive than
      traditional ecotoxicological life cycle end points such as survival and growth.
      Yet, the focus to reduce test duration and to generate more sensitive end points
      has caused transcriptomics studies to be performed at low doses during short
      exposures, separately and independently from traditional ecotoxicity tests,
      making comparisons with life cycle end points indirect. Therefore we aimed to
      directly compare the effects on growth, survival, and gene expression of the
      nonbiting midge Chironomus riparius. To this purpose, we simultaneously analyzed
      life cycle and transcriptomics responses of chironomid larvae exposed to four
      model toxicants. We observed that already at the lowest test concentrations many
      transcripts were significantly differentially expressed, while the life cycle end
      points of C. riparius were hardly affected. Analysis of the differentially
      expressed transcripts showed that at the lowest test concentrations substantial
      and biologically relevant cellular stress was induced and that many transcripts
      responded already maximally at these lowest test concentrations. The direct
      comparison between molecular end life cycle responses after fourteen days of
      exposure revealed that gene expression is more sensitive to toxicant exposure
      than life cycle end points, underlining the potential of transcriptomics for
      ecotoxicity testing and environmental risk assessment.

PMID- 23126639
TI  - Meningioma of geniculate ganglion: case report and review of the literature.
AB  - Although meningioma is a frequent intracranial tumor, it rarely affects the
      geniculate ganglion of the facial nerve. Facial palsy is the most common symptom.
      When hearing is preserved (class A or B, AAO-HNS), tumor is best removed through
      a middle cranial fossa approach. We report the case of a geniculate ganglion
      meningioma and present its clinical, radiological, and pathological features.
      Surgical management is discussed. A literature review revealed that only 17
      previous cases have been reported during the last 50 years.

PMID- 23126640
TI  - The association between parental history of diagnosed mood/anxiety disorders and
      psychiatric symptoms and disorders in young adult offspring.
AB  - BACKGROUND: Parental history of mood or anxiety disorders is one of the strongest
      and most consistent risk factors for the development of these disorders in
      offspring. Gaps remain however in our knowledge of whether maternal or paternal
      disorders are more strongly associated with offspring disorders, and whether the
      association exists in non-clinical samples. This study uses a large population
      based sample to test if maternal or paternal history of mood and/or anxiety
      disorders increases the risk of mood and/or anxiety disorders, or symptoms of
      specific anxiety disorders, in offspring. METHODS: Data were drawn from the
      Nicotine Dependence in Teens Study, a prospective cohort investigation of 1293
      grade 7 students. Data on mental health outcomes were collected in mailed self
      report questionnaires when participants were aged 20.4 (0.7) years on average.
      Parental data were collected in mailed self-report questionnaires. This current
      analysis pertains to 564 participants with maternal and/or paternal data. The
      association between maternal and paternal history and each of diagnosed anxiety
      disorder, diagnosed mood disorder, and symptoms of specific anxiety disorders in
      offspring was studied in multivariate logistic regression. RESULTS: A higher
      proportion of mothers than fathers had a diagnosed mood/anxiety disorder (23%
      versus 12%). Similarly, 14% of female offspring had a diagnosed mood/anxiety
      disorder, compared to 6% of male offspring. The adjusted odds ratio (95%
      confidence interval) for maternal history was 2.2 (1.1, 4.5) for diagnosed mood
      disorders, 4.0 (2.1, 7.8) for diagnosed anxiety disorders, and 2.2 (1.2, 4.0) for
      social phobia symptoms. Paternal history was not associated with any of the
      mental health outcomes in offspring. CONCLUSION: Maternal, but not paternal
      mood/anxiety disorders were associated with diagnosed psychiatric disorders, as
      well as symptoms of specific anxiety disorders, in offspring. Efforts to detect
      mood and anxiety disorders in offspring with a maternal history should be
      encouraged.

PMID- 23126641
TI  - Early life adversity contributes to impaired cognition and impulsive behavior:
      studies from the Oklahoma Family Health Patterns Project.
AB  - BACKGROUND: Stressful early life experience may have adverse consequences in
      adulthood and may contribute to behavioral characteristics that increase
      vulnerability to alcoholism. We examined early life adverse experience in
      relation to cognitive deficits and impulsive behaviors with a reference to risk
      factors for alcoholism. METHODS: We tested 386 healthy young adults (18 to 30
      years of age; 224 women; 171 family history positive for alcoholism) using a
      composite measure of adverse life experience (low socioeconomic status plus
      personally experienced adverse events including physical and sexual abuse and
      separation from parents) as a predictor of performance on the Shipley Institute
      of Living scale, the Stroop color-word task, and a delay discounting task
      assessing preference for smaller immediate rewards in favor of larger delayed
      rewards. Body mass index (BMI) was examined as an early indicator of altered
      health behavior. RESULTS: Greater levels of adversity predicted higher Stroop
      interference scores (F = 3.07, p = 0.048), faster discounting of delayed rewards
      (F = 3.79, p = 0.024), lower Shipley mental age scores (F = 4.01, p = 0.019), and
      higher BMIs in those with a family history of alcoholism (F = 3.40, p = 0.035).
      These effects were not explained by age, sex, race, education, or depression.
      CONCLUSIONS: The results indicate a long-term impact of stressful life experience
      on cognitive function, impulsive behaviors, and early health indicators that may
      contribute to risk in persons with a family history of alcoholism.

PMID- 23126642
TI  - Enabling medication management through health information technology (Health IT).
AB  - OBJECTIVES: The objective of the report was to review the evidence on the impact
      of health information technology (IT) on all phases of the medication management
      process (prescribing and ordering, order communication, dispensing,
      administration and monitoring as well as education and reconciliation), to
      identify the gaps in the literature and to make recommendations for future
      research. DATA SOURCES: We searched peer-reviewed electronic databases, grey
      literature, and performed hand searches. Databases searched included MEDLINE(r),
      Embase, CINAHL (Cumulated Index to Nursing and Allied Health Literature),
      Cochrane Database of Systematic Reviews, International Pharmaceutical Abstracts,
      Compendex, Inspec (which includes IEEE Xplore), Library and Information Science
      Abstracts, E-Prints in Library and Information Science, PsycINFO, Sociological
      Abstracts, and Business Source Complete. Grey literature searching involved
      Internet searching, reviewing relevant Web sites, and searching electronic
      databases of grey literatures. AHRQ also provided all references in their e
      Prescribing, bar coding, and CPOE knowledge libraries. METHODS: Paired reviewers
      looked at citations to identify studies on a range of health IT used to assist in
      the medication management process (MMIT) during multiple levels of screening
      (titles and abstracts, full text and final review for assignment of questions and
      data abstrction). Randomized controlled trials and cohort, case-control, and case
      series studies were independently assessed for quality. All data were abstracted
      by one reviewer and examined by one of two different reviewers with content and
      methods expertise. RESULTS: 40,582 articles were retrieved. After duplicates were
      removed, 32,785 articles were screened at the title and abstract phase. 4,578
      full text articles were assessed and 789 articles were included in the final
      report. Of these, 361 met only content criteria and were listed without further
      abstraction. The final report included data from 428 articles across the seven
      key questions. Study quality varied according to phase of medication management.
      Substantially more studies, and studies with stronger comparative methods,
      evaluated prescribing and monitoring. Clinical decision support systems (CDSS)
      and computerized provider order entry (CPOE) systems were studied more than any
      other application of MMIT. Physicians were more often the subject of evaluation
      than other participants. Other health care professionals, patients, and families
      are important but not studied as thoroughly as physicians. These nonphysicians
      groups often value different aspects of MMIT, have diverse needs, and use systems
      differently. Hospitals and ambulatory clinics were well-represented in the
      literature with less emphasis placed on long-term care facilities, communities,
      homes, and nonhospital pharmacies. Most studies evaluated changes in process and
      outcomes of use, usability, and knowledge, skills, and attitudes. Most showed
      moderate to substantial improvement with implementation of MMIT. Economics
      studies and those with clinical outcomes were less frequently studied. Those
      articles that did address economics and clinical outcomes often showed equivocal
      findings on the effectiveness and cost-effectiveness of MMIT systems. Qualitative
      studies provided evidence of strong perceptions, both positive and negative, of
      the effects of MMIT and unintended consequences. We found little data on the
      effects of forms of medications, conformity, standards, and open source status.
      Much descriptive literature discusses implementation issues but little strong
      evidence exists. Interest is strong in MMIT and more groups and institutions will
      implement systems in the next decades, especially with the Federal Government's
      push toward more health IT to support better and more cost-effective health care.
      CONCLUSIONS: MMIT is well-studied, although on closer examination of the
      literature the evidence is not uniform across phases of medication management,
      groups of people involved, or types of MMIT. MMIT holds the promise of improved
      processes; clinical and economics studies and the understanding of sustainability
      issues are lacking.

PMID- 23126643
TI  - Hepatoma polarization limits CD81 and hepatitis C virus dynamics.
AB  - Many viruses target the polarized epithelial apex during host invasion. In
      contrast, hepatitis C virus (HCV) engages receptors at the basal surface of
      hepatocytes in the polarized liver parenchyma. Hepatocyte polarization limits HCV
      entry by undefined mechanism(s). Given the recent reports highlighting a role for
      receptor mobility in pathogen entry, we studied the effect(s) of hepatocyte
      polarization on viral receptor and HCV pseudoparticle (HCVpp) dynamics using real
      time fluorescence recovery after photobleaching and single particle tracking.
      Hepatoma polarization reduced CD81 and HCVpp dynamics at the basal membrane.
      Since cell polarization is accompanied by changes in the actin cytoskeleton and
      CD81 links to actin via its C-terminus, we studied the dynamics of a mutant CD81
      lacking a C-terminal tail (CD81(DeltaC)) and its effect(s) on HCVpp mobility and
      infection. CD81(DeltaC) showed an increased frequency of confined trajectories
      and a reduction of Brownian diffusing molecules compared to wild-type protein in
      non-polarized cells. However, these changes were notobserved in polarized cells.
      HCVpp showed a significant reduction in Brownian diffusion and infection of
      CD81(DeltaC) expressing non-polarized cells. In summary, these data highlight the
      dynamic nature of CD81 and demonstrate a role for CD81 lateral diffusion to
      regulate HCV infection in a polarization-dependent manner.

PMID- 23126644
TI  - Increased circulating myeloid-derived suppressor cells correlated negatively with
      Th17 cells in patients with rheumatoid arthritis.
AB  - OBJECTIVES: Myeloid-derived suppressor cells (MDSCs) have recently been
      identified as an important mediator in inflammatory and autoimmune diseases
      through the production of arginase (Arg)-1 and inducible nitric oxide synthase
      (iNOS). The aim of this study was to investigate the prevalence of MDSCs in the
      peripheral blood of patients with rheumatoid arthritis (RA) and evaluate their
      correlation with T-helper (Th)17 cells. METHOD: The frequency of MDSCs and Th17
      cells and the mRNA expression of transcriptional factor RORgamma-t and iNOS in
      the peripheral blood of RA patients and healthy controls (HC) were determined by
      flow cytometry and real-time reverse transcription polymerase chain reaction (RT
      PCR), respectively. Plasma levels of interleukin (IL)-17, IL-6, tumour necrosis
      factor (TNF)-alpha, and Arg-1 were analysed by enzyme-linked immunosorbent assays
      (ELISA). RESULTS: Compared with HC, both the prevalence of circulating MDSCs and
      plasma Arg-1 increased significantly in RA patients. However, no significant
      difference was observed in the mRNA level of iNOS between RA patients and HC. The
      frequency of Th17 cells in RA patients was significantly higher than in HC but
      correlated negatively with the frequency of MDSCs and plasma Arg-1. A negative
      correlation between MDSCs and plasma TNF-alpha was also observed. However, the
      frequency of MDSCs was not correlated with plasma IL-6 and IL-17, nor with the
      mRNA level of RORgamma-t. CONCLUSIONS: We found a negative correlation between
      increased circulating MDSCs and Th17 cells in RA patients, which may provide new
      insights into the mechanisms involved in RA.

PMID- 23126645
TI  - Global left ventricular load in asymptomatic aortic stenosis: covariates and
      prognostic implication (the SEAS trial).
AB  - INTRODUCTION: Valvuloarterial impedance (Zva) is a measure of global (combined
      valvular and arterial) load opposing left ventricular (LV) ejection in aortic
      stenosis (AS). The present study identified covariates and tested the prognostic
      significance of global LV load in patients with asymptomatic AS. METHODS: 1418
      patients with mild-moderate, asymptomatic AS in the Simvastatin Ezetimibe in
      Aortic Stenosis (SEAS) study were followed for a mean of 43+/-14 months during
      randomized, placebo-controlled treatment with combined simvastatin 40 mg and
      ezetimibe 10 mg daily. High global LV load was defined as Zva >5 mm Hg/ml/m2. The
      impact of baseline global LV load on rate of major cardiovascular (CV) events,
      aortic valve events and total mortality was assessed in Cox regression models
      reporting hazard ratio (HR) and 95% Confidence Intervals (CI). RESULTS: High
      global LV load was found in 18% (n=252) of patients and associated with female
      gender, higher age, hypertension, more severe AS and lower ejection fraction (all
      p<0.05). A total of 476 major CV events, 444 aortic valve events and 132 deaths
      occurred during follow-up. In multivariate Cox regression analyses, high global
      LV load predicted higher rate of major CV events (HR 1.35 [95% CI 1.08-1.71],
      P=0.010) and aortic valve events (HR 1.41 [95% CI 1.12-1.79], P=0.004)
      independent of hypertension, LV ejection fraction, female gender, age, abnormal
      LV geometry and AS severity, but failed to predict mortality. CONCLUSION: In
      asymptomatic AS, assessment of global LV load adds complementary information on
      prognosis to that provided by hypertension or established prognosticators like AS
      severity and LV ejection fraction.

PMID- 23126646
TI  - Active surveillance for small renal tumors: have clinical concerns been addressed
      so far?
AB  - The incidence of small renal masses is increasing, as a result of the wide
      adoption of imaging exams. Their management, however, is complicated, especially
      in patients with decreased life expectancy or comorbidities. Approximately 20% of
      small renal masses are benign and, even if malignant, just 10% show aggressive
      pathological features. Furthermore, competing cause mortality seems to exceed the
      cancer-specific mortality in patients aged over 70 years. The role of
      percutaneous tumor biopsy is still not well defined. All these observations raise
      the concern as to whether surgery might represent an overtreatment for some cases
      of small renal masses, calling into question the role of active surveillance. The
      aim of this review was to evaluate the current evidence pertaining to several hot
      questions that need to be addressed when contemplating active surveillance for
      small renal masses. The most relevant publications on this subject available in
      the literature were selected. Five representative series of active surveillance
      along with the main related variables were identified. Some relevant items
      surrounding the field of active surveillance were identified and submitted to an
      evidence-based discussion. According to the recent evidence, small renal masses
      under active surveillance tend to show an indolent course with a low probability
      of disease progression, the latter being triggered most of the time by a tendency
      to grow faster. Unfortunately, we are currently unable to predict those few cases
      with aggressive behavior. According to the current evidence, active surveillance
      is feasible and safe in elderly and comorbid patients.

PMID- 23126647
TI  - Transition of care for acute stroke and myocardial infarction patients: from
      hospitalization to rehabilitation, recovery, and secondary prevention.
AB  - OBJECTIVES: To review the available published literature to assess whether
      evidence supports a beneficial role for coordinated transition of care services
      for the postacute care of patients hospitalized with first or recurrent stroke or
      myocardial infarction (MI). This review was framed around five areas of
      investigation: (1) key components of transition of care services, (2) evidence
      for improvement in functional outcomes, morbidity, mortality, and quality of
      life, (3) associated risks or potential harms, (4) evidence for improvement in
      systems of care, and (5) evidence that benefits and harms vary by patient-based
      or system-based characteristics. DATA SOURCES: MEDLINE((r)), CINAHL((r)),
      Cochrane Database of Systematic Reviews, and Embase((r)). REVIEW METHODS: We
      included studies published in English from 2000 to 2011 that specified postacute
      hospitalization transition of care services as well as prevention of recurrent
      stroke or MI. RESULTS: A total of 62 articles representing 44 studies were
      included for data abstraction. Transition of care interventions were grouped into
      four categories: (1) hospital -initiated support for discharge was the initial
      stage in the transition of care process, (2) patient and family education
      interventions were started during hospitalization but were continued at the
      community level, (3) community-based models of support followed hospital
      discharge, and (4) chronic disease management models of care assumed the
      responsibility for long-term care. Early supported discharge after stroke was
      associated with reduced total hospital length of stay without adverse effects on
      functional recovery, and specialty care after MI was associated with reduced
      mortality. Because of several methodological shortcomings, most studies did not
      consistently demonstrate that any specific intervention resulted in improved
      patient-or system -based outcomes. Some studies included more than one
      intervention, which made it difficult to determine the effect of individual
      components on clinical outcomes. There was inconsistency in the definition of
      what constituted a component of transition of care compared to "standard care."
      Standard care was poorly defined, and nearly all studies were underpowered to
      demonstrate a statistical benefit. The endpoints varied greatly from study to
      study. Nearly all the studies were single-site based, and most (26 of 44) were
      conducted in countries with national health care systems quite different from
      that of the U.S., therefore limiting their generalizability. CONCLUSIONS:
      Although a basis for the definition of transition of care exists, more consensus
      is needed on the definition of the interventions and the outcomes appropriate to
      those interventions. There was limited evidence that two components of hospital
      initiated support for discharge (early supported discharge after stroke and
      specialty care followup after MI)were associated with beneficial effects. No
      other interventions had sufficient evidence of benefit based on the findings of
      this systematic review. The adoption of a standard set of definitions, a
      refinement in the methodology used to study transition of care, and appropriate
      selection of patient-centered and policy-relevant outcomes should be employed to
      draw valid conclusions pertaining to specific components of transition of care.

PMID- 23126648
TI  - Discovery of (2S,3R)-N-[2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]oct-3
      yl]benzo[b]furan-2-carboxamide (TC-5619), a selective alpha7 nicotinic
      acetylcholine receptor agonist, for the treatment of cognitive disorders.
AB  - (2S,3R)-N-[2-(Pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]oct-3-yl]benzo[b]furan-2
      carboxamide (7a, TC-5619), a novel selective agonist of the alpha7 neuronal
      nicotinic acetylcholine receptor, has been identified as a promising drug
      candidate for the treatment of cognitive impairment associated with neurological
      disorders. 7a demonstrated more than a thousand-fold separation between the
      affinities for the alpha7 and alpha4beta2 receptor subtypes and had no detectable
      effects on muscle or ganglionic nicotinic receptor subtypes, indicating a marked
      selectivity for the central nervous system over the peripheral nervous system.
      Results obtained from homology modeling and docking explain the observed
      selectivity. 7a had positive effects across cognitive, positive, and negative
      symptoms of schizophrenia in animal models and was additive or synergistic with
      the antipsychotic clozapine. Compound 7a, as an augmentation therapy to the
      standard treatment with antipsychotics, demonstrated encouraging results on
      measures of negative symptoms and cognitive dysfunction in schizophrenia and was
      well tolerated in a phase II clinical proof of concept trial in patients with
      schizophrenia.

PMID- 23126649
TI  - Redox thermodynamics of high-spin and low-spin forms of chlorite dismutases with
      diverse subunit and oligomeric structures.
AB  - Chlorite dismutases (Clds) are heme b-containing oxidoreductases that convert
      chlorite to chloride and dioxygen. In this work, the thermodynamics of the one
      electron reduction of the ferric high-spin forms and of the six-coordinate low
      spin cyanide adducts of the enzymes from Nitrobacter winogradskyi (NwCld) and
      Candidatus "Nitrospira defluvii" (NdCld) were determined through
      spectroelectrochemical experiments. These proteins belong to two phylogenetically
      separated lineages that differ in subunit (21.5 and 26 kDa, respectively) and
      oligomeric (dimeric and pentameric, respectively) structure but exhibit similar
      chlorite degradation activity. The E degrees ' values for free and cyanide-bound
      proteins were determined to be -119 and -397 mV for NwCld and -113 and -404 mV
      for NdCld, respectively (pH 7.0, 25  degrees C). Variable-temperature
      spectroelectrochemical experiments revealed that the oxidized state of both
      proteins is enthalpically stabilized. Molecular dynamics simulations suggest that
      changes in the protein structure are negligible, whereas solvent reorganization
      is mainly responsible for the increase in entropy during the redox reaction.
      Obtained data are discussed with respect to the known structures of the two Clds
      and the proposed reaction mechanism.

PMID- 23126650
TI  - Enabling health care decisionmaking through clinical decision support and
      knowledge management.
AB  - OBJECTIVES: To catalogue study designs used to assess the clinical effectiveness
      of CDSSs and KMSs, to identify features that impact the success of CDSSs/KMSs, to
      document the impact of CDSSs/KMSs on outcomes, and to identify knowledge types
      that can be integrated into CDSSs/KMSs. DATA SOURCES: MEDLINE((r)), CINAHL((r)),
      PsycINFO((r)), and Web of Science((r)). REVIEW METHODS: We included studies
      published in English from January 1976 through December 2010. After screening
      titles and abstracts, full-text versions of articles were reviewed by two
      independent reviewers. Included articles were abstracted to evidence tables by
      two reviewers. Meta-analyses were performed for seven domains in which sufficient
      studies with common outcomes were included. RESULTS: We identified 15,176
      articles, from which 323 articles describing 311 unique studies including 160
      reports on 148 randomized control trials (RCTs) were selected for inclusion. RCTs
      comprised 47.5 percent of the comparative studies on CDSSs/KMSs. Both
      commercially and locally developed CDSSs effectively improved health care process
      measures related to performing preventive services (n = 25; OR 1.42, 95%
      confidence interval [CI] 1.27 to 1.58), ordering clinical studies (n = 20; OR
      1.72, 95% CI 1.47 to 2.00), and prescribing therapies (n = 46; OR 1.57, 95% CI
      1.35 to 1.82). Fourteen CDSS/KMS features were assessed for correlation with
      success of CDSSs/KMSs across all endpoints. Meta-analyses identified six new
      success features: Integration with charting or order entry system. Promotion of
      action rather than inaction. No need for additional clinician data entry.
      Justification of decision support via research evidence. Local user involvement.
      Provision of decision support results to patients as well as providers. Three
      previously identified success features were confirmed: Automatic provision of
      decision support as part of clinician workflow. Provision of decision support at
      time and location of decisionmaking. Provision of a recommendation, not just an
      assessment. Only 29 (19.6%) RCTs assessed the impact of CDSSs on clinical
      outcomes, 22 (14.9%) assessed costs, and 3 assessed KMSs on any outcomes. The
      primary source of knowledge used in CDSSs was derived from structured care
      protocols. CONCLUSIONS: Strong evidence shows that CDSSs/KMSs are effective in
      improving health care process measures across diverse settings using both
      commercially and locally developed systems. Evidence for the effectiveness of
      CDSSs on clinical outcomes and costs and KMSs on any outcomes is minimal. Nine
      features of CDSSs/KMSs that correlate with a successful impact of clinical
      decision support have been newly identified or confirmed.

PMID- 23126653
TI  - An evidence review of active surveillance in men with localized prostate cancer.
AB  - BACKGROUND: Radical prostatectomy and radiation therapy for prostate cancer have
      side effects and unclear survival benefits for early stage and low-risk disease.
      Prostate cancer often has an indolent natural history, making observational
      management strategies potentially appealing. PURPOSE: To systematically review
      the role of active surveillance for triggers to begin curative treatment in men
      with low-risk prostate cancer. Key Questions address changes in prostate cancer
      characteristics over time, definitions of active surveillance and other
      observational strategies, factors affecting the offer of, acceptance of, and
      adherence to active surveillance, the comparative effectiveness of active
      surveillance with curative treatments, and research gaps. DATA SOURCES:
      MEDLINE((r)), Cochrane Central Register of Controlled Trials, Cochrane Database
      of Systematic Reviews, and existing systematic reviews, evidence reports, and
      economic evaluations. STUDY SELECTION: Randomized controlled trials and
      nonrandomized comparative studies of treatments, multivariable association
      studies, and studies of temporal trends in prostate cancer natural history. Only
      published, peer-reviewed, English-language articles were selected based on
      predetermined eligibility criteria. DATA EXTRACTION: A standardized protocol was
      used to extract details on design, diagnoses, interventions, predictive factors,
      outcomes, and study validity. DATA SYNTHESIS: In total, 80 studies provided
      information on epidemiologic trends; 56 on definitions of active surveillance; 42
      on factors affecting the offer of, acceptance of, or adherence to observational
      management strategies; and 26 on comparative effectiveness. Increased diagnosis
      of early-stage prostate cancer due to prostate-specific antigen (PSA) testing,
      led to an increase in prostate cancer incidence from the mid-1980s to the mid
      1990s. The prostate cancer-specific mortality rate decreased for all age groups
      from the early-1990s to 1999. Currently, patients are diagnosed with earlier
      stage and lower risk prostate cancers compared to the pre-PSA era. Over time, a
      lower proportion of men received observational management versus active
      treatment, even among those with low-risk disease. There was no standardized
      definition of active surveillance. Sixteen cohorts used different monitoring
      protocols, all with different combinations of periodic digital rectal
      examination, PSA testing, rebiopsy, and/or imaging findings. Predictors that a
      patient received no initial active treatment generally included older age,
      presence of comorbidities, lower Gleason score, lower tumor stage, lower
      diagnostic PSA, and lower disease progression risk group. No trial provided
      results comparing men with localized disease on active surveillance with surgery
      or radiation therapy. LIMITATIONS: Because of the nonstandardized usages of the
      terms "active surveillance" and "watchful waiting" and their intended and often
      mixed (both curative and palliative) treatment objectives, it was difficult to
      determine which study patients received active monitoring for triggers indicative
      of curative treatment and which observation for clinical symptoms indicative of
      palliative treatment. CONCLUSIONS: More men are being diagnosed with early stage
      prostate cancer. Whether active monitoring with a curative intent is an
      appropriate option for these men remains unclear. A standard, universally agreed
      upon definition of active surveillance that clearly distinguishes it from
      watchful waiting and other observational management strategies is needed to help
      clarify scientific discourse on this topic. Ongoing clinical trials may provide
      information on the comparative effectiveness of active surveillance compared to
      immediate active treatment, but will require long term followup.

PMID- 23126652
TI  - Sex and gonadal hormones in mouse models of Alzheimer's disease: what is relevant
      to the human condition?
AB  - Biologic sex and gonadal hormones matter in human aging and diseases of aging
      such as Alzheimer's - and the importance of studying their influences relates
      directly to human health. The goal of this article is to review the literature to
      date on sex and hormones in mouse models of Alzheimer's disease (AD) with an
      exclusive focus on interpreting the relevance of findings to the human condition.
      To this end, we highlight advances in AD and in sex and hormone biology, discuss
      what these advances mean for merging the two fields, review the current mouse
      model literature, raise major unresolved questions, and offer a research
      framework that incorporates human reproductive aging for future studies aimed at
      translational discoveries in this important area. Unraveling human relevant
      pathways in sex and hormone-based biology may ultimately pave the way to novel
      and urgently needed treatments for AD and other neurodegenerative diseases.

PMID- 23126654
TI  - Modifications of a conserved regulatory network involving INDEHISCENT controls
      multiple aspects of reproductive tissue development in Arabidopsis.
AB  - Disrupting pollen tube growth and fertilization in Arabidopsis plants leads to
      reduced seed set and silique size, providing a powerful genetic system with which
      to identify genes with important roles in plant fertility. A transgenic
      Arabidopsis line with reduced pollen tube growth, seed set and silique growth was
      used as the progenitor in a genetic screen to isolate suppressors with increased
      seed set and silique size. This screen generated a new allele of INDEHISCENT
      (IND), a gene originally identified by its role in valve margin development and
      silique dehiscence (pod shatter). IND forms part of a regulatory network that
      involves several other transcriptional regulators and involves the plant hormones
      GA and auxin. Using GA and auxin mutants that alter various aspects of
      reproductive development, we have identified novel roles for IND, its paralogue
      HECATE3, and the MADS box proteins SHATTERPROOF1/2 in flower and fruit
      development. These results suggest that modified forms of the regulatory network
      originally described for the Arabidopsis valve margin, which include these genes
      and/or their recently evolved paralogs, function in multiple components of
      GA/auxin-regulated reproductive development.

PMID- 23126655
TI  - Minor histocompatibility antigen UTY as target for graft-versus-leukemia and
      graft-versus-haematopoiesis in the canine model.
AB  - Male patients with female-stem-cell donors have better prognosis compared to
      female-to-male combinations due to Y-encoded minor histocompatibility antigens
      recognized by female-alloimmune-effector lymphocytes in the context of a graft
      versus-leukemia (GvL) effect. We provide data in a dog-model that the minor
      histocompatibility antigen UTY might be a promising target to further improve GvL
      immune reactions after allogeneic-stem-cell transplantations. Female-canine-UTY
      specific T cells (CTLs) were stimulated in vitro using autologous-DCs loaded with
      three HLA-A2-restricted-UTY-derived peptides (3-fold-expansion), and specific T
      cell responses were determined in 3/6 female dogs. CTLs specifically
      recognized/lysed autologous-female-peptide-loaded DCs, but not naive-autologous
      female DCs and monocytes. They mainly recognized bone-marrow (BM) and to a lower
      extent DCs, monocytes, PBMCs and B-cells from DLA-identical-male littermates and
      peptide-loaded T2-cells in an MHC-I-restricted manner. A UTY-/male-specific
      reactivity was also obtained in vivo after stimulation of a female dog with DLA
      identical-male PBMCs. In summary, we demonstrated natural UTY processing and
      presentation in dogs. We showed that female-dog CTLs were specifically stimulated
      by HLA-A2-restricted-UTY peptides, thereby enabling recognition of DLA-identical
      male cells, mainly BM cells. These observations suggest UTY as a promising
      candidate-antigen to improve GvL-reactions in the course of immunotherapy.

PMID- 23126656
TI  - Self-reported outcomes of trans-tibial amputations for non-reconstructable
      Charcot neuroarthropathy in patients with diabetes: a preliminary report.
AB  - AIMS: Lower-extremity amputation in patients with diabetes is associated with
      premature mortality and impaired ambulatory status. Despite advances in limb
      salvage techniques, certain patients will require major amputation. The
      hypothesis of this study is that self-reported outcomes of patients with non
      reconstructable Charcot neuroarthropathy and chronic osteomyelitis improve after
      trans-tibial amputation. METHODS: Self-reported outcome was assessed using the
      Medical Outcome Study Short Form 36-item health survey (SF-36) and the Foot and
      Ankle Ability Measure. The study group included 13 patients with diabetes who
      underwent a trans-tibial amputation and completed both the Medical Outcome Study
      SF-36 and the Foot and Ankle Measure pre- and post-operatively. RESULTS:
      Significant improvement after trans-tibial amputation occurred in the SF-36
      Physical Component Summary score and both the Foot and Ankle Measure Activity of
      Daily Living and Sports scores at a mean follow-up of 79 weeks (range 53-122
      weeks). Although the SF-36 Mental Component Summary score improved, the
      improvement did not achieve statistical significance (P = 0.30). Twelve of the 13
      patients were satisfied with the amputation and had no reservations. CONCLUSIONS:
      In a select group of Charcot neuroarthropathy patients with chronic
      osteomyelitis, trans-tibial amputation resulted in improvement in self-reported
      outcomes. Although major lower-extremity amputation is a devastating complication
      in patients with diabetes, the results of this study provides some evidence for
      optimism in these high-risk patients.

PMID- 23126657
TI  - A novel organ preservation for small partial liver transplantations in rats:
      venous systemic oxygen persufflation with nitric oxide gas.
AB  - The prognosis for recipients of small liver grafts is poor. The aim of this study
      was to determine the impact of venous systemic oxygen persufflation (VSOP) with
      nitric oxide (NO) gas for 30% partial liver preservation and transplantation in
      rats. After we determined optimal NO concentration as 40 ppm in vitro with the
      isolated perfused rat liver model, we assessed liver injury and regeneration in
      vivo at 1, 3, 24 and 168 h after transplantation in the following three groups
      after 3 h-cold storage (n = 20 per group): control group = static storage; VSOP
      group = oxygen persufflation and VSOP+NO group = oxygen with NO persufflation.
      The liver graft persufflation was achieved with medical gas via the suprahepatic
      vena cava; In comparison with control group after transplantation, VSOP+NO
      preservation (1) increased portal circulation, (2) reduced AST and ALT release,
      (3) upregulated hepatic endothelial NO synthase, (4) reduced hepatocyte and
      bileductule damage and (5) improved liver regeneration. These results suggest
      that gaseous oxygen with NO persufflation is a novel and safe preservation method
      for small partial liver grafts, not only alleviating graft injury but also
      improve liver regeneration after transplantation.

PMID- 23126658
TI  - Socially sensitive lactation: exploring the social context of breastfeeding.
AB  - Many women report difficulties with breastfeeding and do not maintain the
      practice for as long as intended. Although psychologists and other researchers
      have explored some of the difficulties they experience, fuller exploration of the
      relational contexts in which breastfeeding takes place is warranted to enable
      more in-depth analysis of the challenges these pose for breastfeeding women. This
      article is based on qualitative data collected from 22 first-time breastfeeding
      mothers through two phases of interviews and audio-diaries which explored how the
      participants experienced their relationships with significant others and the
      wider social context of breastfeeding in the first five weeks postpartum. Using a
      thematic analysis informed by symbolic interactionism, we develop the overarching
      theme of 'Practising socially sensitive lactation' which captures how
      participants felt the need to manage tensions between breastfeeding and their
      perceptions of the needs, expectations and comfort of others. We argue that
      breastfeeding remains a problematic social act, despite its agreed importance for
      child health. While acknowledging the limitations of our sample and analytic
      approach, we suggest ways in which perinatal and public health interventions can
      take more effective account of the social challenges of breastfeeding in order to
      facilitate the health and psychological well-being of mothers and their infants.

PMID- 23126659
TI  - A reference genetic map of C. clementina hort. ex Tan.; citrus evolution
      inferences from comparative mapping.
AB  - BACKGROUND: Most modern citrus cultivars have an interspecific origin. As a
      foundational step towards deciphering the interspecific genome structures, a
      reference whole genome sequence was produced by the International Citrus Genome
      Consortium from a haploid derived from Clementine mandarin. The availability of a
      saturated genetic map of Clementine was identified as an essential prerequisite
      to assist the whole genome sequence assembly. Clementine is believed to be a
      'Mediterranean' mandarin * sweet orange hybrid, and sweet orange likely arose
      from interspecific hybridizations between mandarin and pummelo gene pools. The
      primary goals of the present study were to establish a Clementine reference map
      using codominant markers, and to perform comparative mapping of pummelo, sweet
      orange, and Clementine. RESULTS: Five parental genetic maps were established from
      three segregating populations, which were genotyped with Single Nucleotide
      Polymorphism (SNP), Simple Sequence Repeats (SSR) and Insertion-Deletion (Indel)
      markers. An initial medium density reference map (961 markers for 1084.1 cM) of
      the Clementine was established by combining male and female Clementine
      segregation data. This Clementine map was compared with two pummelo maps and a
      sweet orange map. The linear order of markers was highly conserved in the
      different species. However, significant differences in map size were observed,
      which suggests a variation in the recombination rates. Skewed segregations were
      much higher in the male than female Clementine mapping data. The mapping data
      confirmed that Clementine arose from hybridization between 'Mediterranean'
      mandarin and sweet orange. The results identified nine recombination break points
      for the sweet orange gamete that contributed to the Clementine genome.
      CONCLUSIONS: A reference genetic map of citrus, used to facilitate the chromosome
      assembly of the first citrus reference genome sequence, was established. The high
      conservation of marker order observed at the interspecific level should allow
      reasonable inferences of most citrus genome sequences by mapping next-generation
      sequencing (NGS) data in the reference genome sequence. The genome of the haploid
      Clementine used to establish the citrus reference genome sequence appears to have
      been inherited primarily from the 'Mediterranean' mandarin. The high frequency of
      skewed allelic segregations in the male Clementine data underline the probable
      extent of deviation from Mendelian segregation for characters controlled by
      heterozygous loci in male parents.

PMID- 23126660
TI  - Th2 cytokine antagonists: potential treatments for severe asthma.
AB  - INTRODUCTION: Asthma is a major disease burden worldwide. Treatment with steroids
      and long acting beta-agonists effectively manage symptoms in many patients but do
      not treat the underlying cause of disease and have serious side effects when used
      long term and in children. Therapies targeting the underlying causes of asthma
      are urgently needed. T helper type 2 (Th2) cells and the cytokines they release
      are clinically linked to the presentation of all forms of asthma. They are the
      primary drivers of mild to moderate and allergic asthma. They also play a
      pathogenetic role in exacerbations and more severe asthma though other factors
      are also involved. Much effort using animal models and human studies has been
      dedicated to the identification of the pathogenetic roles of these cells and
      cytokines and whether inhibition of their activity has therapeutic benefit in
      asthma. AREAS COVERED: We discuss the current status of Th2 cytokine antagonists
      for the treatment of asthma. We also discuss the potential for targeting Th2
      inducing cytokines, Th2 cell receptors and signaling as well as the use of Th2
      cell antagonists, small interfering oligonucleotides, microRNAs, and combination
      therapies. EXPERT OPINION: Th2 antagonists may be most effective in particular
      asthma subtypes/endotypes where specific cytokines are known to be active through
      the analysis of biomarkers. Targeting common receptors and pathways used by these
      cytokines may have additional benefit. Animal models have been valuable in
      identifying therapeutic targets in asthma, however the results from such studies
      need to be carefully interpreted and applied to appropriately stratified patient
      cohorts in well-designed clinical studies and trials.

PMID- 23126661
TI  - Alpinia officinarum inhibits adipocyte differentiation and high-fat diet-induced
      obesity in mice through regulation of adipogenesis and lipogenesis.
AB  - Although Alpinia officinarum has been used in traditional medicine for the
      treatment of several conditions, such as abdominal pain, emesis, diarrhea,
      impaired renal function, and dysentery, little is known about its function in
      obesity. In this study, we investigated the antiobesity effect of A. officinarum
      ethanol extract (AOE) on lipid accumulation in 3T3-L1 cells and obesity in mice
      fed a high-fat diet (HFD). AOE dose-dependently suppressed lipid accumulation
      during differentiation of 3T3-L1 preadipocytes by downregulating CCAAT enhancer
      binding protein alpha (C/EBPalpha), sterol regulatory element binding protein-1
      (SREBP-1), and peroxisome proliferator-activated receptor-gamma (PPAR-gamma)
      genes. Galangin, a major component of A. officinarum, had antiadipogenic effects
      in 3T3-L1 cells. AOE supplementation in mice fed a HFD revealed that AOE
      significantly decreased HFD-induced increases in body, liver, and white adipose
      tissue weights and decreased serum insulin and leptin levels. To elucidate the
      inhibitory mechanism of AOE in obesity, lipid metabolism-related genes were
      identified. AOE efficiently suppressed protein expressions of C/EBPalpha, fatty
      acid synthase, SREBP-1, and PPAR-gamma in the liver and adipose tissue. The
      protein expression patterns, observed by immunoblot, were confirmed by
      quantitative real-time polymerase chain reaction. Collectively, these results
      suggest that AOE prevents obesity by suppressing adipogenic and lipogenic genes.
      AOE has potential for use as an antiobesity therapeutic agent that can function
      by regulating lipid metabolism.

PMID- 23126662
TI  - Fermenting red ginseng enhances its safety and efficacy as a novel skin care anti
      aging ingredient: in vitro and animal study.
AB  - The objective of this study was to evaluate the anti-aging potential and skin
      safety of red ginseng (RG) and fermented red ginseng (FRG) using Lactobacillus
      brevis for use as cosmetic ingredients. Concentrations of uronic acid,
      polyphenols, and flavonoids, and antioxidant activities were greater in FRG
      compared to RG. The contents of total ginsenosides were not significantly
      different. However, the ginsenoside metabolite content was higher in FRG
      (14,914.3 MUg/mL) compared to RG (5697.9 MUg/mL). The tyrosinase inhibitory
      activity (IC(50)) of FRG was 27.63 MUg/mL, and more potent compared with RG
      (34.14 MUg/mL), (P<.05). The elastase inhibitory activity (IC(50)) of FRG was
      117.07 MUg/mL also higher compared with RG (157.90 MUg/mL). In a primary skin
      irritation test, 10% RG and 10% FRG were classified as practically nonirritating
      materials. In a skin sensitization test, the RG group showed a sensitization rate
      of 100% and its mean evaluation score of irritation was 1.4, whereas the FRG
      group showed 20% and 0.2%, respectively. By fermentation of RG, FRG has increased
      contents of ginsenoside metabolites, such as Rg3, Rg5, Rk1, compound K, Rh1, F2,
      Rg2, and flavonoids content. Therefore, FRG offers increased anti-wrinkle
      efficacy, whitening efficacy, and reduced toxicological potency compared to RG.

PMID- 23126663
TI  - Effects of Ecklonia cava polyphenol in individuals with hypercholesterolemia: a
      pilot study.
AB  - We evaluated the efficacy and safety of Ecklonia cava polyphenol (SeapolynolTM, a
      polyphenol antioxidant and anti-inflammatory agent purified from E. cava) during
      a 12-week treatment period (400 mg orally once daily) in individuals with
      hypercholesterolemia and performed subgroup analysis for metabolic syndrome
      (MetS). As a noncomparative study, forty-six individuals (M:F=22:24, mean
      age=54+/-11 years) with fasting total cholesterol concentration >240 mg/dL or low
      density lipoprotein cholesterol (LDL-C) concentration >130 mg/dL were enrolled.
      Hip circumference (100+/-7 cm vs. 98+/-7 cm, P<.01), total cholesterol (244+/-25
      mg/dL vs. 225+/-37 mg/dL, P<.01), LDL-C (161+/-24 mg/dL vs. 146+/-34 mg/dL,
      P<.01), and C-reactive protein (2.51+/-3.55 mg/L vs. 1.37+/-1.32 mg/L, P<.05)
      were significantly decreased without significant adverse effect. A differential
      assessment according to the presence [MetS(+) group, n=18] and absence [MetS(-)
      group, n=28] of MetS showed that Hb(A1c) decreased significantly following 12
      week Seapolynol treatment in the MetS(+) compared with the MetS(-) group (-0.3%+/
      0.5% vs. 0.1%+/-0.3%, P<.01). In conclusion, although our results showed that
      Seapolynol treatment is effective and safe without significant adverse events or
      abnormal laboratory findings during a 12-week period in individuals with
      hypercholesterolemia, more research in a larger population with a longer-term
      follow-up period in a randomized placebo-controlled study is needed to confirm
      the results.

PMID- 23126664
TI  - Dried tomato-flavored probiotic cream cheese with Lactobacillus paracasei.
AB  - A dried tomato-flavored probiotic cream cheese (P) containing Lactobacillus
      paracasei Lpc-37 was developed for the purpose of this study. The same product,
      but without probiotic addition (C) was used as control. Lactococcus lactis subsp.
      lactis and Lactococcus lactis subsp. cremoris were used as lactic starter
      cultures. Chemical composition analyses and sensory tests were performed on days
      1 and 7, respectively. Titratable acidity, pH value and L. paracasei population
      were determined every 7 d during the refrigerated storage (21 d) of the cream
      cheeses. The experiment and analyses were performed in triplicate, using standard
      methods. Probiotic population remained greater than 10(7) CFU/g throughout the
      storage period, thereby characterizing the product as potentially probiotic.
      Cream cheeses C and P did not differ on the sensory tests, both obtaining good
      overall acceptance by the consumers, of which 82.6% stated that they certainly or
      probably would buy the product. PRACTICAL APPLICATION: Lactobacillus paracasei
      Lpc-37 is a probiotic bacterium and clinical studies have shown that this
      microorganism beneficially affects its host. In general, dried tomato-flavored
      products and cream cheese are products with good acceptance by the consumers.
      Thus, regular consumption of the probiotic cream cheese developed in this study
      may have positive effects on health and well being of people if incorporated into
      their diet.

PMID- 23126666
TI  - Superior effect of combination vs. single steroid therapy in keloid disease: a
      comparative in vitro analysis of glucocorticoids.
AB  - Keloid disease (KD) is a fibroproliferative disorder of unknown etiology. Current
      use of corticosteroid injection is partially beneficial with 80% recurrence rate.
      Additionally, the efficacy of different steroids, alone or in combination as
      opposed to monotherapy, in treating KD remains unclear. Here, we compared the
      single and combined efficacy of glucocorticoids-dexamethasone (Dex),
      triamcinolone (TAC), and methylprednisolone (Medrol)-on primary keloid
      fibroblasts (KFs) (n = 27) and normal skin (n = 19) fibroblasts at cellular,
      protein, and messenger RNA levels in vitro. Our results demonstrated that
      cytotoxicity to steroids was dose dependent. Cell spreading, attachment, and
      proliferation were significantly (p < 0.05) reduced by Medrol and TAC. Migration
      and invasion properties of KF were inhibited significantly (p < 0.05) by Medrol
      and TAC compared with Dex. At both protein and messenger RNA levels, keloid
      associated fibrotic markers were significantly (p < 0.05) decreased by Medrol and
      TAC compared with Dex. However, vascular endothelial growth factor expression was
      significantly (p = 0.01) decreased by Dex compared with TAC and Medrol. Medrol
      and TAC caused significant (p < 0.04) apoptosis, whereas Dex inhibited the UV
      induced apoptosis and up-regulated survivin. Blocking of glucocorticoid receptor
      by RU486 inhibited cytoprotective property of Dex and apoptotic properties of TAC
      and Medrol. Double treatment with Dex + TAC and Dex + Medrol significantly (p <
      0.05) induced apoptosis. In conclusion, this is the first study to report the
      efficacy of three well-known steroids on KF and suggest that combination may be
      superior than using a single steroid in treating KD.

PMID- 23126667
TI  - The Coxiella burnetii type IV secretion system substrate CaeB inhibits intrinsic
      apoptosis at the mitochondrial level.
AB  - Manipulation of host cell apoptosis is a virulence property shared by many
      intracellular pathogens to ensure productive replication. For the obligate
      intracellular pathogen Coxiella burnetii anti-apoptotic activity, which depends
      on a functional type IV secretion system (T4SS), has been demonstrated.
      Accordingly, the C. burnetii T4SS effector protein AnkG was identified to inhibit
      pathogen-induced apoptosis, possibly by binding to the host cell mitochondrial
      protein p32 (gC1qR). However, it was unknown whether AnkG alone is sufficient for
      apoptosis inhibition or if additional effector proteins are required. Here, we
      identified two T4SS effector proteins CaeA and CaeB (C. burnetii anti-apoptotic
      effector) that inhibit the intrinsic apoptotic pathway. CaeB blocks apoptosis
      very efficiently, while the anti-apoptotic activity of CaeA is weaker. Our data
      suggest that CaeB inhibits apoptosis at the mitochondrial level, but does not
      bind to p32. Taken together, our results demonstrate that C. burnetii harbours
      several anti-apoptotic effector proteins and suggest that these effector proteins
      use different mechanism(s) to inhibit apoptosis.

PMID- 23126668
TI  - Effect of surface charge on the interfacial orientation and conformation of FB1
      in model membranes.
AB  - The toxicity of FB1 is usually explained through the enzymatic disruption of
      lipidic metabolism. However, it may lie in the thermodynamics of the membrane and
      its cooperative phase behavior rather than in the activity of individual
      proteins. Here, we investigate the effects of FB1 at the molecular and mesoscopic
      levels in FB1-phospholipid mixed Langmuir films. Mean molecular area vs FB1 molar
      fractions (x(FB1)) and phase diagram analysis allowed us to define miscibility
      conditions and phase states at different x(FB1). Surface potential measurements,
      evaluated as a function of the molecular packing and x(FB1), revealed the FB1
      induced change in the collective dipolar reorientation leaded to neutralization
      of charged films. Size, shape, and distribution of 2D-domain analysis from
      epifluorescence data suggested the increase in the mixing entropy and film
      relaxation rate. Finally, PM-IRRAS revealed the orientation of FB1 with the amine
      end (zwitterionic and negatively charged monolayers) or the tricarballylic acid
      end (positively charged monolayers) pointing to the air. The globular-extended
      conformational equilibrium of FB1 is dynamically defined by the membrane charge
      becoming a toxicity enhancing factor. The specificity of the toxin-protein
      interaction might also be perturbed by the FB1-induced remodeling of the membrane
      topography by affecting the raft-like platforms where membrane enzymes are
      considered to be located.

PMID- 23126669
TI  - High blood pressure and resilience to physical and cognitive decline in the
      oldest old: the Leiden 85-plus Study.
AB  - OBJECTIVES: To evaluate the association between various blood pressure (BP)
      measures at age 85 and future decline in physical and cognitive function the
      oldest old. DESIGN: Longitudinal study. SETTING: The population-based Leiden 85
      plus Study. PARTICIPANTS: Five hundred seventy-two 85-year-old community-dwelling
      individuals. MEASUREMENTS: BP was measured at age 85 during home visits.
      Activities of daily living (ADLs) and Mini-Mental State Examination (MMSE) were
      assessed at age 85 and annually thereafter up to age 90. On average, participants
      were followed for 3.2 years. Cross-sectional and longitudinal analyses were
      performed using linear regression models using systolic BP (SBP), diastolic BP
      (DBP), mean arterial pressure (MAP), and pulse pressure (PP) as the determinants.
      All analyses were adjusted for sociodemographic and cardiovascular factors.
      RESULTS: At age 85, higher SBP and PP were associated with lower ADL disability
      scores (both P = .01). Similarly, higher SBP, DBP, and MAP were associated with
      higher MMSE scores (all P < .05). From age 85 onward, higher SBP (P < .001), MAP
      (P = .01), and PP (P = .003) at age 85 were associated with lower annual
      increases in ADL disability scores. Likewise, higher SBP (P = .03) and PP (P =
      .008) at age 85 were associated with lower annual declines in MMSE scores.
      Additional analyses showed that the association between high BP and lower annual
      decline in MMSE score was most pronounced in participants with high ADL
      disability. CONCLUSION: In the oldest old, higher SBP and PP are associated with
      resilience to physical and cognitive decline, especially in individuals with pre
      existing physical disability.

PMID- 23126670
TI  - Simultaneous release of Fe and As during the reductive dissolution of Pb-As
      jarosite by Shewanella putrefaciens CN32.
AB  - Jarosites are produced during metallurgical processing, on oxidized sulfide
      deposits, and in acid mine drainage environments. Despite the environmental
      relevance of jarosites, few studies have examined their biogeochemical stability.
      This study demonstrates the simultaneous reduction of structural Fe(III) and
      aqueous As(V) during the dissolution of synthetic Pb-As jarosite
      (PbFe(3)(SO(4),AsO(4))(2)(OH)(6)) by Shewanella putrefaciens using batch
      experiments under anaerobic circumneutral conditions. Fe(III) reduction occurred
      immediately in inoculated samples while As(V) reduction was observed after 72 h.
      XANES spectra showed As(III) (14.7%) in the solid phase at 168 h coincident with
      decreased aqueous As(V). At 336 h, XANES spectra and aqueous speciation analysis
      demonstrated 20.2% and 3.0% of total As was present as As(III) in the solid and
      aqueous phase, respectively. In contrast, 12.4% of total Fe was present as
      aqueous Fe(II) and was below the detection limits of XANES in the solid phase.
      TEM-EDS analysis at 336 h showed secondary precipitates enriched in Fe and O with
      minor amounts of As and Pb. Based on experimental data and thermodynamic
      modeling, we suggest that structural Fe(III) reduction was thermodynamically
      driven while aqueous As(V) reduction was triggered by detoxification induced to
      offset the high As(V) (328 MUM) concentrations released during dissolution.

PMID- 23126671
TI  - L-DNA molecular beacon: a safe, stable, and accurate intracellular nano
      thermometer for temperature sensing in living cells.
AB  - Noninvasive and accurate measurement of intracellular temperature is of great
      significance in biology and medicine. This paper describes a safe, stable, and
      accurate intracellular nano-thermometer based on an L-DNA molecular beacon (L
      MB), a dual-labeled hairpin oligonucleotide built from the optical isomer of
      naturally occurring d-DNA. Relying on the temperature-responsive hairpin
      structure and the FRET signaling mechanism of MBs, the fluorescence of L-MBs is
      quenched below the melting temperature and enhanced with increasing temperature.
      Because of the excellent reversibility and tunable response range, L-MBs are very
      suitable for temperature sensing. More importantly, the non-natural L-DNA
      backbone prevents the L-MBs from binding to cellular nucleic acids and proteins
      as well as from being digested by nucleases inside the cells, thus ensuring
      excellent stability and accuracy of the nano-thermometer in a complex cellular
      environment. The L-MB nano-thermometer was used for the photothermal study of Pd
      nanosheets in living cells, establishing the nano-thermometer as a useful tool
      for intracellular temperature measurement.

PMID- 23126672
TI  - A predictive model of Vibrio cholerae for combined temperature and organic
      nutrient in aquatic environments.
AB  - AIMS: To develop a predictive model for Vibrio cholerae in sea water. METHODS AND
      RESULTS: The growth curves of V. cholerae NE-9 at different temperatures (range
      from 10 to 30 degrees C) and chemical oxygen demand (COD) concentration (range
      from 5 to 40 mg l(-1) ) were determined. The modified logistic model and Baranyi
      model were chosen to regress the growth curves. A new method for modelling
      effects of temperature and COD on the specific growth rate (MU) was successfully
      developed by a combination of modified square root-type equation and saturation
      growth rate model. The coefficient of determination (R(2) ), bias factor (Bf) and
      accuracy factor (Af) were taken to assess the performance of the established
      model. Logistic model produced a good fit to the observed data (R(2) = 0.952).
      However, the Baranyi model provided biologically plausible parameter estimates.
      The overall predictions for V. cholerae NE-9 growth agreed well with observed
      plate counts, and the average R(2) , Bf and Af values were 0.967, 1.198 and
      1.201, respectively. CONCLUSION: The predicted model agreed well with observed
      data, and the result can be applied for the prediction of V. cholerae in actual
      environments. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of this study
      provide the basis for the prediction of V. cholerae in sea water.

PMID- 23126673
TI  - Modulation of alpha5 subunit-containing GABAA receptors alters alcohol drinking
      by rhesus monkeys.
AB  - BACKGROUND: Alcohol's ability to potentiate the activity of gamma-aminobutyric
      acid (GABA) at GABAA receptors has been implicated as a key mechanism underlying
      the behavioral effects of alcohol. The complex molecular biology of these
      receptors raises the possibility that particular receptor subtypes may play
      unique roles in alcohol's abuse-related effects and that subtype-selective
      ligands with therapeutic specificity against alcohol might be developed. This
      study evaluated the capacity of alpha5GABAA receptor ligands to alter selectively
      the reinforcing effects of alcohol. METHODS: Two groups of rhesus monkeys were
      trained to orally self-administer alcohol or sucrose under fixed-ratio schedules
      and limited daily access conditions. In addition, following daily self
      administration sessions, the behavior of each monkey was scored for both species
      typical and drug-induced behaviors. RESULTS: Concentrations of 1 to 6% alcohol
      maintained self-administration above water levels, engendered pharmacologically
      relevant blood alcohol levels ranging from 90 to 160 mg/dl, and produced changes
      in behavior typical of alcohol intoxication. Concentrations of 0.3 to 3% sucrose
      also reliably maintained self-administration. The alpha5GABAA receptor agonist QH
      ii-066 enhanced and the alpha5GABAA receptor inverse agonist L-655,708 inhibited
      alcohol, but not sucrose drinking. The changes in alcohol drinking could be
      reversed with the alpha5GABAA receptor antagonist XLi-093. However, L-655,708
      increased yawning in both alcohol and sucrose drinkers, possibly indicative of an
      anxiogenic effect. CONCLUSIONS: These findings suggest a prominent and specific
      role for alpha5GABAA receptor mechanisms in the reinforcing effects of alcohol.
      Moreover, these results suggest that alpha5GABAA receptors may represent a novel
      pharmacological target for the development of medications to reduce drinking. Of
      ligands modulating this receptor, alpha5GABAA receptor inverse agonists may hold
      the most promise as alcohol pharmacotherapies.

PMID- 23126674
TI  - Metabolic syndrome and its association with fatty liver disease after orthotopic
      liver transplantation.
AB  - The metabolic syndrome (MetS) might contribute to morbidity after orthotopic
      liver transplantation (OLT). For this reason, we searched for MetS-associated
      risk factors and analyzed the link with nonalcoholic fatty liver disease (NAFLD)
      in OLT recipients. De novo MetS affected 32.9% of our cohort (n = 170) within 2
      years after OLT. Multivariate analysis identified glycosylated hemoglobin (HbA1c)
      levels >=5% [odds ratio (OR) = 3.5; 95% confidence interval (CI) = 1.56-8.13, P =
      0.003], diabetes mellitus (OR = 4.31, CI = 1.69-10.99, P = 0.002), and arterial
      hypertension (OR = 4.59, CI = 1.46-14.49, P = 0.009) as independent risk factors
      for de novo MetS. MetS incidence correlated with steroid dosage after OLT (5.2 +/
      2.4 mg/day vs. 7.1 +/- 4.7 mg/day, P = 0.014), and was linked to NAFLD (P =
      0.001) via obesity (OR = 4.67, CI = 1.55-14.1, P = 0.006) and dyslipidemia (OR =
      4.23, CI = 1.35-13.3, P = 0.013) post-OLT. In conclusion, we were able to
      identify low threshold HbA1c as a novel risk factor for MetS after OLT and
      described a link of MetS with NAFLD in transplant organs. This study also
      indicated that steroid treatment is associated with MetS rates after OLT.

PMID- 23126675
TI  - Magnetic bead-based salivary peptidome profiling for periodontal-orthodontic
      treatment.
AB  - BACKGROUND: Patients with periodontitis seek periodontal-orthodontic treatment
      to address certain functional and aesthetic problems. However, little is known of
      the effect of periodontitis on orthodontic treatment. Thus, we compared the
      differences in peptide mass fingerprints of orthodontic patients with and without
      periodontitis by MALDI-TOF MS using a magnetic bead-based peptidome analysis of
      saliva samples. In this way, we aimed to identify and explore a panel of
      differentially-expressed specific peptides. RESULTS: Saliva samples from 24
      patients (eight orthodontic patients without periodontitis, eight with
      periodontitis and another eight with periodontitis but no orthodontic treatment)
      were analyzed, and peptide mass fingerprints were created by scanning MS signals
      using matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF MS) combined with magnetic beads. Nine mass peaks showed
      significant differences. Orthodontic patients in the group without periodontal
      disease showed higher mass peaks for seven peptides of the nine, whereas the mass
      peaks for the other two peptides were higher in the periodontal-orthodontic
      patients. Besides, these differentially-expressed peptides were sequenced.
      CONCLUSIONS: The elucidated candidate biomarkers indicated interactions between
      periodontal condition and orthodontic treatment and their contributions to the
      changes of saliva protein profiles. Our results provide novel insight into the
      altered salivary protein profile during periodontal-orthodontic treatment, and
      may lead to the development of a therapeutic monitoring strategy for periodontics
      and orthodontics.

PMID- 23126676
TI  - The effects of reminiscence therapy on depressive symptoms of Chinese elderly:
      study protocol of a randomized controlled trial.
AB  - BACKGROUND: Depression is one of the most common mental disorders with a high
      prevalence among the older adults. In recent years, after realizing some side
      effects of the antidepressants, non-pharmacological psychological treatments
      begin to attract accruing attention. Reminiscence therapy is one of the
      psychological treatments that specially designed for the elderly to improve their
      mental health status by recalling and assessing their existing memory. Though
      some studies indicate reminiscence therapy can be effective and beneficial for
      the mental health of elderly, the conclusions are not consistent yet. The aim of
      this research is to assess the effectiveness of reminiscence therapy for Chinese
      elderly. METHODS: Sixty older adults (>=60 years of age) with mild to moderate
      depression will be randomly assigned to an experimental or a control condition.
      The participants in the experiment group will receive the reminiscence therapy
      under the Watt's protocol with adaptation to Chinese Culture which consists of
      six weekly sessions of 90 minutes each. The control group will be treated as
      before. An assessor who is blind to intervention will conduct the measures before
      treatment, after treatment immediately, and three months after treatment.
      DISCUSSION: This study will provide the evidence whether the reminiscence therapy
      is effective to treat depressive symptoms of Chinese elderly. This research has
      been registered in the clinicaltrials.gov (NCT01553669).

PMID- 23126677
TI  - Higher motivation - greater control? The effect of arousal on judgement.
AB  - This research examines control over the effect of arousal, a dimension of affect,
      on judgement. Past research shows that high processing motivation enhances
      control over the effects of affect on judgement. Isolating and studying arousal
      as opposed to valence, the other dimension of affect, and its effect on
      judgement, we identify boundary conditions for past findings. Drawing from the
      literature on processes by which arousal influences judgement, we demonstrate
      that the role of motivation is contingent upon the type of judgement task (i.e.,
      memory- versus stimulus-based judgement). In stimulus-based judgement,
      individuals exert greater control over the effect of arousal on judgement under
      low compared to high motivation. In contrast, in memory-based judgement
      individuals exert greater control over the effect of arousal under high compared
      to low motivation. Theoretical implications and avenues for future research are
      discussed.

PMID- 23126678
TI  - Investigating the role of T7 and T12 residues on the biological properties of
      thrombin-binding aptamer: enhancement of anticoagulant activity by a single
      nucleobase modification.
AB  - An acyclic pyrimidine analogue, containing a five-member cycle fused on the
      pyrimidine ring, was synthesized and introduced at position 7 or 12 of the 15-mer
      oligodeoxynucleotide GGTTGGTGTGGTTGG, known as thrombin-binding aptamer (TBA).
      Characterization by 1H NMR and CD spectroscopies of the resulting aptamers, TBA
      T7b and TBA-T12b, showed their ability to fold into the typical antiparallel
      chairlike G-quadruplex structure formed by TBA. The apparent CD melting
      temperatures indicated that the introduction of the acyclic residue, mainly at
      position 7, improves the thermal stability of resulting G-quadruplexes with
      respect to TBA. The anticoagulant activity of the new molecules was then valued
      in PT assay, and it resulted that TBA-T7b is more potent than TBA in prolonging
      clotting time. On the other hand, in purified fibrinogen assay the thrombin
      inhibitory activity of both modified sequences was lower than that of TBA using
      human enzyme, whereas the potency trend was again reversed using bovine enzyme.
      Obtained structure-activity relationships were investigated by structural and
      computational studies. Taken together, these results reveal the active role of
      TBA residues T7 and T12 and the relevance of some amino acids located in the
      anion binding exosite I of the protein in aptamer-thrombin interaction.

PMID- 23126679
TI  - Mechanism of benzylic hydroxylation by 4-hydroxymandelate synthase. A
      computational study.
AB  - Hydroxymandelate synthase (HMS) and 4-hydroxyphenylpyruvate dioxygenase (HPPD)
      are highly related enzymes using the same substrates but catalyzing hydroxylation
      reactions yielding different products. The first steps of the HMS and HPPD
      catalytic reactions are believed to proceed in the same way and lead to an
      Fe(IV)?O-hydroxyphenylacetate (HPA) intermediate. Further down the catalytic
      cycles, HMS uses Fe(IV)?O to perform hydroxylation of the benzylic carbon,
      whereas in HPPD, the reactive oxoferryl intermediate attacks the aromatic ring of
      HPA. This study focuses on this part of the HMS catalytic cycle that starts from
      the oxoferryl intermediate and aims to identify interactions within the active
      site that are responsible for enzyme specificity. To this end, a HMS-Fe(IV)?O-HPA
      complex was modeled with molecular dynamics simulations. On the basis of the
      molecular dynamics-equilibrated structure, an active site model suitable for
      quantum chemical investigations was constructed and used for density functional
      theory (B3LYP) calculations of the mechanism of the native reaction of HMS, i.e.,
      benzylic hydroxylation, and the alternative electrophilic attack on the ring,
      which is a step of the HPPD catalytic cycle. The most important result of this
      study is the finding that the conformation of the Ser201 side chain in the second
      coordination shell has a key role in directing the reaction of Fe(IV)?O into
      either the HMS or the HPPD channel.

PMID- 23126680
TI  - Strategies to identify long noncoding RNAs involved in gene regulation.
AB  - Long noncoding RNAs (lncRNAs) have been detected in nearly every cell type and
      found to be fundamentally involved in many biological processes. The
      characterization of lncRNAs has immense potential to advance our comprehensive
      understanding of cellular processes and gene regulation, along with implications
      for the treatment of human disease. The recent ENCODE (Encyclopedia of DNA
      Elements) study reported 9,640 lncRNA loci in the human genome, which corresponds
      to around half the number of protein-coding genes. Because of this sheer number
      and their functional diversity, it is crucial to identify a pool of potentially
      relevant lncRNAs early on in a given study. In this review, we evaluate the
      methods for isolating lncRNAs by immunoprecipitation and review the advantages,
      disadvantages, and applications of three widely used approaches - microarray,
      tiling array, and RNA-seq - for identifying lncRNAs involved in gene regulation.
      We also look at ways in which data from publicly available databases such as
      ENCODE can support the study of lncRNAs.

PMID- 23126682
TI  - Functional limitations and physical symptoms of individuals with chronic pain.
AB  - OBJECTIVES: Chronic pain is a debilitating condition that may cause additional
      symptoms affecting the sufferers' working capacity and quality of life. Studying
      the prevalence and consequences of chronic pain in various populations remains
      important for a complete picture of the global burden imposed by chronic pain
      conditions. METHODS: We investigated the prevalence of self-reported chronic pain
      conditions in Iceland in addition to symptoms and functional limitations within
      the group, using a population-based random sample. A questionnaire was mailed to
      9807 Icelanders aged 18-79 years and, of these, 5906 participated in the study.
      Chronic pain was considered manifest in people reporting chronic low back pain,
      chronic neck symptoms, and/or fibromyalgia. Prevalence calculations were weighted
      with respect to gender, age, and residential area to represent the underlying
      population. Associations of chronic pain conditions with symptoms and functional
      limitations were measured with adjusted logistic regression models, contrasting
      symptoms in individuals reporting any of the three pain conditions with those who
      did not. RESULTS: The population-estimated prevalence of chronic pain condition
      was 19.9% with distinct gender differences (men = 15.2%, women = 24.7%). Several
      symptoms and functional limitations in daily life were strongly associated with
      chronic pain, including deficient energy and muscular discomfort, physical
      mobility limitations, lifting groceries, climbing stairs, and stooping. Women,
      but not men, with chronic pain tended to refrain from physical activity.
      CONCLUSIONS: Chronic pain is a prevalent condition and those who report chronic
      pain generally suffer from ill health and limitations in their daily life
      compared to individuals not suffering from the condition.

PMID- 23126683
TI  - Molecular analysis of the parallel domestication of the common bean (Phaseolus
      vulgaris) in Mesoamerica and the Andes.
AB  - We have studied the nucleotide diversity of common bean, Phaseolus vulgaris,
      which is characterized by two independent domestications in two geographically
      distinct areas: Mesoamerica and the Andes. This provides an important model, as
      domestication can be studied as a replicate experiment. We used nucleotide data
      from five gene fragments characterized by large introns to analyse 214 accessions
      (102 wild and 112 domesticated). The wild accessions represent a cross-section of
      the entire geographical distribution of P. vulgaris. A reduction in genetic
      diversity in both of these gene pools was found, which was three-fold greater in
      Mesoamerica compared with the Andes. This appears to be a result of a bottleneck
      that occurred before domestication in the Andes, which strongly impoverished this
      wild germplasm, leading to the minor effect of the subsequent domestication
      bottleneck (i.e. sequential bottleneck). These findings show the importance of
      considering the evolutionary history of crop species as a major factor that
      influences their current level and structure of genetic diversity. Furthermore,
      these data highlight a single domestication event within each gene pool. Although
      the findings should be interpreted with caution, this evidence indicates the
      Oaxaca valley in Mesoamerica, and southern Bolivia and northern Argentina in
      South America, as the origins of common bean domestication.

PMID- 23126684
TI  - Relationship of seminal reactive nitrogen and oxygen species and total
      antioxidant capacity with sperm DNA fragmentation in infertile couples with
      normal and abnormal sperm parameters.
AB  - The objective of this study was to investigate the association between the amount
      of superoxide anion, peroxynitrite as oxidative stress (OS) markers and total
      antioxidant capacity (TAC) with sperm DNA fragmentation in infertile men with
      abnormal semen parameters. Semen samples were obtained from 102 infertile couples
      and divided into groups with normal and abnormal semen parameters according to
      the World Health Organization (WHO). Peroxynitrite and superoxide anions were
      detected using spectrofluorometric assays combined with 2,7 dicholorofluorescein
      (DCF)-DA and 4-chloro-7-nitrobenzo-2-oxa -1, 3-diazole (NBD-CL). Colorimetric
      assay was used for evaluation of TAC, while DNA fragmentation was studied by
      using sperm chromatin dispersion test. Superoxide anion, peroxynitrite and DNA
      fragmentation were significantly higher in infertile couples with abnormal semen
      parameters as compared to infertile couples with normal semen (P < 0.01). TAC was
      significantly lower in infertile men with abnormal semen parameters (P < 0.01).
      There was also a significant positive correlation between OS markers with sperm
      DNA fragmentation (r = 0.59, P < 0.01 and r = 0.67, P < 0.01, respectively). We
      have found that imbalance between superoxide anion and peroxynitrite with
      antioxidant capacity in infertile men with abnormal sperm parameters is
      associated with higher sperm DNA fragmentation.

PMID- 23126685
TI  - An efficient rice mutagenesis system based on suspension-cultured cells.
AB  - Plant mutants are important bio-resources for crop breeding and gene functional
      studies. Conventional methods for generating mutant libraries by mutagenesis of
      seeds with physical or chemical agents are of low efficiency. Here, we developed
      a highly-efficient ethyl methanesulfonate (EMS) mutagenesis system based on
      suspension-cultured cells, with rice (Oryza sativa L.) as an example. We show
      that treatment of suspension-cultured tiny cell clusters with 0.4% EMS for 18-22
      h followed by differentiation and regeneration produced as high as 29.4%
      independent mutant lines with visible phenotypic variations, including a number
      of important agronomic traits such as grain size, panicle size, grain or panicle
      shape, tiller number and angle, heading date, male sterility, and disease
      sensitivity. No mosaic mutant was observed in the mutant lines tested. In this
      mutant library, we obtained a mutant with an abnormally elongated uppermost
      internode. Sequencing and functional analysis revealed that this is a new allelic
      mutant of eui (elongated uppermost internode) caused by two point mutations in
      the first exon of the EUI gene, representing a successful example of this
      mutagenesis system.

PMID- 23126687
TI  - Novel pharmacological approaches for treatment of obstructive sleep apnea in
      children.
AB  - INTRODUCTION: The lymphadenoid tissues in the upper airway are sparse and
      organized lympho-epithelial structures playing an important role against foreign
      pathogens, with the palatine tonsils being the major components of the lymphoid
      tissues contained in the Waldeyer's ring. Obstructive sleep apnea (OSA) has
      emerged as a very frequent condition in the pediatric age range that is
      associated with substantial neurobehavioral, cardiovascular and metabolic
      morbidities. Adenotonsillar hypertrophy is the major pathophysiological
      contributor to OSA occurrence in children. AREAS COVERED: Here, the authors
      provide a systematic review and summary of some of the known histological and
      pathological features of human lymphadenoid tissues and their fundamental
      immunological functions, provide insights into the pathophysiology of pediatric
      OSA, particularly focusing on inflammatory pathways and the available outcomes
      associated with targeting such pathways with compounds such as corticosteroids
      and leukotriene modifiers. Furthermore, they present findings from an unbiased
      approach to discovery of therapeutic targets and formulate constructs toward
      putative future interventional approaches for this highly prevalent condition.
      EXPERT OPINION: Surgical approaches for pediatric OSA may not be as effective as
      previously anticipated. Accordingly, expanded use of existing systemic or topical
      anti-inflammatory agents or development of novel compounds targeting selected
      immune cell populations underlying pathophysiological determinants of OSA is
      needed.

PMID- 23126688
TI  - Communication: A vibrational study of propargyl cation using the vacuum
      ultraviolet laser velocity-map imaging photoelectron method.
AB  - By employing the vacuum ultraviolet (VUV) laser velocity-map imaging
      photoelectron (VUV-VMI-PE) method, we have obtained a vibrationally resolved
      photoelectron spectrum of gaseous propargyl radical [C(3)H(3)(X(2)B(1))] in the
      energy range of 0-4600 cm(-1) above its ionization energy. The cold C(3)H(3)
      radicals were produced from a supersonically cooled radical beam source based on
      193 nm ArF photodissociation of C(3)H(3)Cl. The VUV-VMI-PE spectrum of C(3)H(3)
      thus obtained reveals a Franck-Condon factor (FCF) pattern with a highly dominant
      origin band along with weak vibrational progressions associated with excitations
      of the C-C nu(5)(+)(a(1)) and C=C nu(3)(+)(a(1)) symmetric stretching modes and
      the CCH nu(7)(+)(b(1)) out-of-plane bending mode of C(3)H(3)(+)(X(1)A(1)). The
      nu(5)(+)(a(1)) vibrational frequency of 1120 cm(-1) determined in the present
      study is lower than the value deduced from the recent Ar-tagged infrared
      photodissociation study by 102 cm(-1), confirming the highly accurate vibrational
      frequency predictions obtained by the most recent state-of-the-art ab initio
      quantum calculations. The observation of the FCF disallowed nu(7)(+)(b(1)) mode
      is indicative of vibronic interactions. The discrepancy observed between the FCF
      pattern determined in the present study and that predicted by a recent high-level
      quantum theoretical investigation can be taken as evidence that the potential
      energy surfaces used in the latter theoretical study are in need of improvement
      in order to provide a reliable FCF prediction for the C(3)H(3)/C(3)H(3)(+)
      photoionization system.

PMID- 23126686
TI  - Intensification of diabetes medication and risk for 30-day readmission.
AB  - AIM: To examine the association of in-hospital diabetes regimen intensification
      with subsequent 30-day risk for unplanned readmission/emergency department
      admission. METHODS: We retrospectively studied 1949 adults with Type 2 diabetes
      receiving primary care within an academic health network admitted to the hospital
      between January 2007 and December 2009. Glucose therapy intensification was
      defined as new start of insulin or oral hypoglycaemic agents, or addition of
      prandial insulin or insulin mixtures. The association of glucose therapy
      intensification with subsequent 30-day risk for unplanned readmission/emergency
      department admission was examined, with focus on medicine service patients with
      poorly controlled glycaemia (baseline HbA(1c)  >= 64 mmol/mol). RESULTS: One in
      six patients (324/1949, 17%) had early readmission/emergency department
      admission. Compared with patients without early readmission, readmitted patients
      were more often male (58 vs. 52%, P = 0.03), had higher Charlson co-morbidity
      score [mean (sd) 3.0 (2.0) vs. 2.8 (1.8), P = 0.02], longer length of stay [5
      (4.4) vs. 3.9 (3.3) days, P < 0.01] and were more often discharged home with
      nursing services (38 vs. 32%, P = 0.03). Overall, glucose therapy intensification
      was not associated with early hospital readmission/emergency department admission
      (odds ratio 0.94, 95% CI 0.64-1.37, P = 0.74). However, among medicine service
      patients with baseline HbA(1c)  >= 64 mmol/mol (8%), glucose therapy
      intensification was associated with a significantly decreased early readmission
      risk (adjusted odds ratio 0.33, 95% CI 0.12-0.88, P = 0.03) and lower post
      discharge HbA(1c)  {mean decrease (sd): 20 (26) mmol/mol [1.8 (2.4)%] vs. 7 (15)
      mmol/mol [0.6 (1.4)%], P < 0.01}. CONCLUSIONS: Diabetes medical regimen
      intensification during hospitalization was not associated with early readmission.
      Among patients with elevated HbA(1c) , glucose therapy intensification was
      associated with a decreased 30-day readmission/emergency department admission
      risk and lower outpatient HbA(1c)  levels. Our findings support the safety and
      durable impact of diabetes regimen optimization during hospital admission.

PMID- 23126689
TI  - Stochastic mapping of first order reaction networks: a systematic comparison of
      the stochastic and deterministic kinetic approaches.
AB  - Stochastic maps are developed and used for first order reaction networks to
      decide whether the deterministic kinetic approach is appropriate for a certain
      evaluation problem or the use of the computationally more demanding stochastic
      approach is inevitable. On these maps, the decision between the two approaches is
      based on the standard deviation of the expectation of detected variables: when
      the relative standard deviation is larger than 1%, the use of the stochastic
      method is necessary. Four different systems are considered as examples: the
      irreversible first order reaction, the reversible first order reaction, two
      consecutive irreversible first order reactions, and the unidirectional triangle
      reaction. Experimental examples are used to illustrate the practical use of the
      theoretical results. It is shown that the maps do not only depend on particle
      numbers, but the influence of parameters such as time, rate constants, and the
      identity of the detected target variable is also an important factor.

PMID- 23126690
TI  - The embedded many-body expansion for energetics of molecular crystals.
AB  - Reliable prediction of molecular crystal energetics is a vital goal for
      computational chemistry. Here we show that accurate results can be obtained from
      a monomer-based many-body expansion truncated at the two-body level, with the
      monomer and dimer calculations suitably embedded in a model of the crystalline
      environment. By including the two dominant effects--electrostatics and exchange
      repulsion--we are able to capture the important nonadditive terms in the energy,
      and approach very closely results from full periodic second-order Moller-Plesset
      calculations. The advantage of the current scheme is that extension to coupled
      cluster and explicitly correlated F12 methods is completely straightforward. We
      demonstrate the approach through calculations on carbon dioxide, hydrogen
      fluoride, and ice XIh and XIc. In accord with previous studies, we find these two
      ice polymorphs to be very close in energy, with our periodic coupled-cluster
      single double triple-F12 calculation giving the hexagonal structure more stable
      by around 0.3 kJ mol(-1).

PMID- 23126691
TI  - Arbitrary order El'yashevich-Wilson B tensor formulas for the most frequently
      used internal coordinates in molecular vibrational analyses.
AB  - In recent years, internal coordinates have become the preferred means of
      expressing potential energy surfaces. The ability to transform quantities from
      chemically significant internal coordinates to primitive Cartesian coordinates
      and spectroscopically relevant normal coordinates is thus critical to the further
      development of computational chemistry. In the present work, general nth order
      formulas are presented for the Cartesian derivatives of the five most commonly
      used internal coordinates--bond stretching, bond angle, torsion, out-of-plane
      angle, and linear bending. To compose such formulas in a reasonably
      understandable fashion, a new notation is developed that is a generalization of
      that which has been used previously for similar purposes. The notation developed
      leads to easily programmable and reasonably understandable arbitrary order
      formulas, yet it is powerful enough to express the arbitrary order B tensor of a
      general, N-point internal coordinate, as is done herein. The techniques employed
      in the derivation of such formulas are relatively straightforward, and could
      presumably be applied to a number of other internal coordinates as needed.

PMID- 23126692
TI  - Symmetry-adapted perturbation theory based on unrestricted Kohn-Sham orbitals for
      high-spin open-shell van der Waals complexes.
AB  - Two open-shell formulations of the symmetry-adapted perturbation theory are
      presented. They are based on the spin-unrestricted Kohn-Sham (SAPT(UKS)) and
      unrestricted Hartree-Fock (SAPT(UHF)) descriptions of the monomers, respectively.
      The key reason behind development of SAPT(UKS) is that it is more compatible with
      density functional theory (DFT) compared to the previous formulation of open
      shell SAPT based on spin-restricted Kohn-Sham method of Zuchowski et al. [J.
      Chem. Phys. 129, 084101 (2008)]. The performance of SAPT(UKS) and SAPT(UHF) is
      tested for the following open-shell van der Waals complexes: He...NH,
      H(2)O...HO(2), He...OH, Ar...OH, Ar...NO. The results show an excellent agreement
      between SAPT(UKS) and SAPT(ROKS). Furthermore, for the first time SAPT based on
      DFT is shown to be suitable for the treatment of interactions involving Pi-state
      radicals (He...OH, Ar...OH, Ar...NO). In the interactions of transition metal
      dimers ((3)Sigma(u)(+))Au(2) and ((13)Sigma(g)(+))Cr(2) we show that SAPT is
      incompatible with the use of effective core potentials. The interaction energies
      of both systems expressed instead as supermolecular UHF interaction plus
      dispersion from SAPT(UKS) result in reasonably accurate potential curves.

PMID- 23126693
TI  - Harnessing the meta-generalized gradient approximation for time-dependent density
      functional theory.
AB  - Density functionals within the meta-generalized gradient approximation (MGGA) are
      widely used for ground-state electronic structure calculations. However, the
      gauge variance of the kinetic energy density tau confounds applications of MGGAs
      to time-dependent systems, excited states, magnetic properties, and states with
      strong spin-orbit coupling. Becke and Tao used the paramagnetic current density
      to construct a gauge invariant generalized kinetic energy density tau. We show
      that tau(W)<=tau, where tau(W) is the von Weizsacker kinetic energy density of a
      one-electron system. Thus, replacing tau by tau leads to current-dependent MGGAs
      (cMGGAs) that are not only gauge invariant but also restore the accuracy of MGGAs
      in iso-orbital regions for time-dependent and current-carrying states. The
      current dependence of cMGGAs produces a vector exchange-correlation (XC)
      potential in the time-dependent adiabatic Kohn-Sham (KS) equations. While MGGA
      response properties of current-free ground states become manifestly gauge-variant
      to second order, linear response properties are affected by a new XC kernel
      appearing in the cMGGA magnetic orbital rotation Hessian. This kernel reflects
      the first-order coupling of KS orbitals due to changes in the paramagnetic
      current density and has apparently been ignored in previous MGGA response
      implementations. Inclusion of the current dependence increases total computation
      times by less than 50%. Benchmark applications to 109 adiabatic excitation
      energies using the Tao-Perdew-Staroverov-Scuseria (TPSS) MGGA and its hybrid
      version TPSSh show that cMGGA excitation energies are slightly lower than the
      MGGA ones on average, but exhibit fewer outliers. Similarly, the optical
      rotations of 13 small organic molecules show a small but systematic improvement
      upon inclusion of the magnetic XC kernel. We conclude that cMGGAs should replace
      MGGAs in all applications involving time-dependent or current-carrying states.

PMID- 23126694
TI  - A test of systematic coarse-graining of molecular dynamics simulations:
      thermodynamic properties.
AB  - Coarse-graining (CG) techniques have recently attracted great interest for
      providing descriptions at a mesoscopic level of resolution that preserve fluid
      thermodynamic and transport behaviors with a reduced number of degrees of freedom
      and hence less computational effort. One fundamental question arises: how well
      and to what extent can a "bottom-up" developed mesoscale model recover the
      physical properties of a molecular scale system? To answer this question, we
      explore systematically the properties of a CG model that is developed to
      represent an intermediate mesoscale model between the atomistic and continuum
      scales. This CG model aims to reduce the computational cost relative to a full
      atomistic simulation, and we assess to what extent it is possible to preserve
      both the thermodynamic and transport properties of an underlying reference all
      atom Lennard-Jones (LJ) system. In this paper, only the thermodynamic properties
      are considered in detail. The transport properties will be examined in subsequent
      work. To coarse-grain, we first use the iterative Boltzmann inversion (IBI) to
      determine a CG potential for a (1-phi)N mesoscale particle system, where phi is
      the degree of coarse-graining, so as to reproduce the radial distribution
      function (RDF) of an N atomic particle system. Even though the uniqueness theorem
      guarantees a one to one relationship between the RDF and an effective pairwise
      potential, we find that RDFs are insensitive to the long-range part of the IBI
      determined potentials, which provides some significant flexibility in further
      matching other properties. We then propose a reformulation of IBI as a robust
      minimization procedure that enables simultaneous matching of the RDF and the
      fluid pressure. We find that this new method mainly changes the attractive tail
      region of the CG potentials, and it improves the isothermal compressibility
      relative to pure IBI. We also find that there are optimal interaction cutoff
      lengths for the CG system, as a function of phi, that are required to attain an
      adequate potential while maintaining computational speedup. To demonstrate the
      universality of the method, we test a range of state points for the LJ liquid as
      well as several LJ chain fluids.

PMID- 23126695
TI  - A one-parameter quantum cluster equilibrium approach.
AB  - The established quantum cluster equilibrium approach is further developed in this
      work. The equations are reformulated to result in a one-parameter expression,
      i.e., with one of two empirical parameters eliminated. Instead of a parametrized
      constant mean field interaction we present two further approaches using
      temperature dependent mean field functions. The suggested functions are assessed
      by means of two test systems, namely hydrogen fluoride and water which are
      investigated concerning their liquid phase properties as well as the phenomenon
      of evaporation. The obtained thermodynamic data are compared with each other for
      the different mean field functions including the conventional approach as well as
      to experimental data.

PMID- 23126696
TI  - Brownian dynamics simulations with hard-body interactions: spherical particles.
AB  - A novel approach to account for hard-body interactions in (overdamped) Brownian
      dynamics simulations is proposed for systems with non-vanishing force fields. The
      scheme exploits the analytically known transition probability for a Brownian
      particle on a one-dimensional half-line. The motion of a Brownian particle is
      decomposed into a component that is affected by hard-body interactions and into
      components that are unaffected. The hard-body interactions are incorporated by
      replacing the "affected" component of motion by the evolution on a half-line. It
      is discussed under which circumstances this approach is justified. In particular,
      the algorithm is developed and formulated for systems with space-fixed obstacles
      and for systems comprising spherical particles. The validity and justification of
      the algorithm is investigated numerically by looking at exemplary model systems
      of soft matter, namely at colloids in flow fields and at protein interactions.
      Furthermore, a thorough discussion of properties of other heuristic algorithms is
      carried out.

PMID- 23126697
TI  - Adiabatic and nonadiabatic contributions to the energy of a system subject to a
      time-dependent perturbation: complete separation and physical interpretation.
AB  - When a time-dependent perturbation acts on a quantum system that is initially in
      the nondegenerate ground state ?0> of an unperturbed Hamiltonian H(0), the wave
      function acquires excited-state components ?k> with coefficients c(k)(t) exp(
      iE(k)t/h), where E(k) denotes the energy of the unperturbed state ?k>. It is well
      known that each coefficient c(k)(t) separates into an adiabatic term a(k)(t) that
      reflects the adjustment of the ground state to the perturbation--without actual
      transitions--and a nonadiabatic term b(k)(t) that yields the probability
      amplitude for a transition to the excited state. In this work, we prove that the
      energy at any time t also separates completely into adiabatic and nonadiabatic
      components, after accounting for the secular and normalization terms that appear
      in the solution of the time-dependent Schrodinger equation via Dirac's method of
      variation of constants. This result is derived explicitly through third order in
      the perturbation. We prove that the cross-terms between the adiabatic and
      nonadiabatic parts of c(k)(t) vanish, when the energy at time t is determined as
      an expectation value. The adiabatic term in the energy is identical to the total
      energy obtained from static perturbation theory, for a system exposed to the
      instantaneous perturbation lambdaH'(t). The nonadiabatic term is a sum over
      excited states ?k> of the transition probability multiplied by the transition
      energy. By evaluating the probabilities of transition to the excited eigenstates
      ?k'(t)> of the instantaneous Hamiltonian H(t), we provide a physically
      transparent explanation of the result for E(t). To lowest order in the
      perturbation parameter lambda, the probability of finding the system in state
      ?k'(t)> is given by lambda(2) ?b(k)(t)?(2). At third order, the transition
      probability depends on a second-order transition coefficient, derived in this
      work. We indicate expected differences between the results for transition
      probabilities obtained from this work and from Fermi's golden rule.

PMID- 23126698
TI  - Restricted active space spin-flip configuration interaction: theory and examples
      for multiple spin flips with odd numbers of electrons.
AB  - The restricted active space spin flip (RAS-SF) method is extended to allow ground
      and excited states of molecular radicals to be described at low cost (for small
      numbers of spin flips). RAS-SF allows for any number of spin flips and a flexible
      active space while maintaining pure spin eigenfunctions for all states by
      maintaining a spin complete set of determinants and using spin-restricted
      orbitals. The implementation supports both even and odd numbers of electrons,
      while use of resolution of the identity integrals and a shared memory parallel
      implementation allow for fast computation. Examples of multiple-bond
      dissociation, excited states in triradicals, spin conversions in organic multi
      radicals, and mixed-valence metal coordination complexes demonstrate the broad
      usefulness of RAS-SF.

PMID- 23126699
TI  - Mixing atoms and coarse-grained beads in modelling polymer melts.
AB  - We present a simple hybrid model for macromolecules where the single molecules
      are modelled with both atoms and coarse-grained beads. We apply our approach to
      two different polymer melts, polystyrene and polyethylene, for which the coarse
      grained potential has been developed using the iterative Boltzmann inversion
      procedure. Our results show that it is possible to couple the two potentials
      without modifying them and that the mixed model preserves the local and the
      global structure of the melts in each of the case presented. The degree of
      resolution present in each single molecule seems to not affect the robustness of
      the model. The mixed potential does not show any bias and no cluster of particles
      of different resolution has been observed.

PMID- 23126700
TI  - An explicitly correlated approach to basis set incompleteness in full
      configuration interaction quantum Monte Carlo.
AB  - By performing a stochastic dynamic in a space of Slater determinants, the full
      configuration interaction quantum Monte Carlo (FCIQMC) method has been able to
      obtain energies which are essentially free from systematic error to the basis set
      correlation energy, within small and systematically improvable error bars.
      However, the weakly exponential scaling with basis size makes converging the
      energy with respect to basis set costly and in larger systems, impossible. To
      ameliorate these basis set issues, here we use perturbation theory to couple the
      FCIQMC wavefunction to an explicitly correlated strongly orthogonal basis of
      geminals, following the [2](R12) approach of Valeev et al. The required one- and
      two-particle density matrices are computed on-the-fly during the FCIQMC dynamic,
      using a sampling procedure which incurs relatively little additional computation
      expense. The F12 energy corrections are shown to converge rapidly as a function
      of sampling, both in imaginary time and number of walkers. Our pilot calculations
      on the binding curve for the carbon dimer, which exhibits strong correlation
      effects as well as substantial basis set dependence, demonstrate that the
      accuracy of the FCIQMC-F12 method surpasses that of all previous FCIQMC
      calculations, and that the F12 correction improves results equivalent to
      increasing the quality of the one-electron basis by two cardinal numbers.

PMID- 23126701
TI  - Determination of Kohn-Sham effective potentials from electron densities using the
      differential virial theorem.
AB  - We present an accurate method for constructing the Kohn-Sham effective potential
      corresponding to a given electron density in one-dimensional and spherically
      symmetric systems. The method is based on the differential virial theorem--an
      exact relation between the effective potential, the electron density, and the
      kinetic energy density. A distinctive feature of the proposed technique is that
      it employs a size-consistent bosonic reference potential to ensure the correct
      asymptotic behavior of the resulting Kohn-Sham potential. We describe a practical
      implementation of our method and use it to obtain high-quality exchange
      correlation and correlation potentials of the neon and argon atoms from ab initio
      densities generated in large Slater- and Gaussian-type basis sets.

PMID- 23126703
TI  - Efficient simultaneous fluorescence orientation, spectrum, and lifetime detection
      for single molecule dynamics.
AB  - We report on the simultaneous detection of the fluorescence lifetime, spectrum,
      and three-dimensional dipole orientation determination of single perylene diimide
      molecules deposited on a silica surface as a model system for studying
      fluorophore internal and orientational dynamics. We employ a multi-parameter
      detection scheme to demonstrate how jumps in the orientation of the molecule can
      be disentangled from spectral jumps, both leading to changes of the detected
      total fluorescence intensity. The fluorescence lifetime determined simultaneously
      from the same photons is also sensitive to the orientation of the dipole with
      respect to the interface between media with different refractive indices. The
      correlated changes of the lifetime and orientation we observe are in good
      agreement with theory.

PMID- 23126702
TI  - Constant time tensor correlation experiments by non-gamma-encoded recoupling
      pulse sequences.
AB  - Constant-time tensor correlation under magic-angle spinning conditions is an
      important technique in solid-state nuclear magnetic resonance spectroscopy for
      the measurements of backbone or side-chain torsion angles of polypeptides and
      proteins. We introduce a general method for the design of constant-time tensor
      correlation experiments under magic-angle spinning. Our method requires that the
      amplitude of the average Hamiltonian must depend on all the three Euler angles
      bringing the principal axis system to the rotor-fixed frame, which is commonly
      referred to as non-gamma encoding. We abbreviate this novel approach as
      COrrelation of Non-Gamma-Encoded Experiment (CONGEE), which exploits the
      orientation-dependence of non-gamma-encoded sequences with respect to the magic
      angle rotation axis. By manipulating the relative orientation of the average
      Hamiltonians created by two non-gamma-encoded sequences, one can obtain a
      modulation of the detected signal, from which the structural information can be
      extracted when the tensor orientations relative to the molecular frame are known.
      CONGEE has a prominent feature that the number of rf pulses and the total pulse
      sequence duration can be maintained to be constant so that for torsion angle
      determination the effects of systematic errors owing to the experimental
      imperfections and/or T(2) effects could be minimized. As a proof of concept, we
      illustrate the utility of CONGEE in the correlation between the C' chemical shift
      tensor and the C(alpha)-H(alpha) dipolar tensor for the backbone psi angle
      determination. In addition to a detailed theoretical analysis, numerical
      simulations and experiments measured for [U-(13)C, (15)N]-L-alanine and N-acetyl
      [U-(13)C, (15)N]-D,L-valine are used to validate our approach at a spinning
      frequency of 20 kHz.

PMID- 23126704
TI  - Spectroscopy of 3, 4, 9, 10-perylenetetracarboxylic dianhydride (PTCDA) attached
      to rare gas samples: clusters vs. bulk matrices. I. Absorption spectroscopy.
AB  - The interaction between 3, 4, 9, 10-perylenetetracarboxylic dianhydride (PTCDA)
      and rare gas or para-hydrogen samples is studied by means of laser-induced
      fluorescence excitation spectroscopy. The comparison between spectra of PTCDA
      embedded in a neon matrix and spectra attached to large neon clusters shows that
      these large organic molecules reside on the surface of the clusters when doped by
      the pick-up technique. PTCDA molecules can adopt different conformations when
      attached to argon, neon, and para-hydrogen clusters which implies that the
      surface of such clusters has a well-defined structure without liquid or fluxional
      properties. Moreover, a precise analysis of the doping process of these clusters
      reveals that the mobility of large molecules on the cluster surface is quenched,
      preventing agglomeration and complex formation.

PMID- 23126705
TI  - Spectroscopy of 3, 4, 9, 10-perylenetetracarboxylic dianhydride (PTCDA) attached
      to rare gas samples: clusters vs. bulk matrices. II. Fluorescence emission
      spectroscopy.
AB  - The interaction between 3, 4, 9, 10-perylenetetracarboxylic dianhydride (PTCDA)
      molecules and solid rare gas samples is studied by means of fluorescence emission
      spectroscopy. Laser-excited PTCDA-doped large argon, neon, and para-hydrogen
      clusters along with PTCDA embedded in helium nanodroplets are spectroscopically
      characterized with respect to line broadening and shifting. A fast non-radiative
      relaxation is observed before a radiative decay in the electronic ground state
      takes place. In comparison, fluorescence emission studies of PTCDA embedded in
      bulk neon and argon matrices result in much more complex spectral signatures
      characterized by a splitting of the different emission lines. These can be
      assigned to the appearance of site isomers of the surrounding matrix lattice
      structure.

PMID- 23126706
TI  - Nonlocal electron-phonon coupling in the pentacene crystal: beyond the Gamma
      point approximation.
AB  - There is currently increasing interest in understanding the impact of the
      nonlocal (Peierls-type) electron-phonon mechanism on charge transport in organic
      molecular semiconductors. Most estimates of the non-local coupling constants
      reported in the literature are based on the Gamma-point phonon modes. Here, the
      influence of phonon modes spanning the entire Brillouin zone (phonon dispersion)
      on the nonlocal electron-phonon couplings is investigated for the pentacene
      crystal. The phonon modes are obtained by using a supercell approach. The results
      underline that the overall nonlocal couplings are substantially underestimated by
      calculations taking sole account of the phonons at the Gamma point of the unit
      cell. The variance of the transfer integrals based on Gamma-point normal-mode
      calculations at room temperature is underestimated in some cases by 40% for
      herringbone-type dimers and by over 80% for cofacial dimers. Our calculations
      show that the overall coupling is somewhat larger for holes than for electrons.
      The results also suggest that the interactions of charge carriers (both electrons
      and holes) with acoustic and optical phonons are comparable. Therefore, an
      adequate description of the charge-transport properties in pentacene and similar
      systems requires that these two electron-phonon coupling mechanisms be treated on
      the same footing.

PMID- 23126707
TI  - Probing the structural and electronic properties of small vanadium dioxide
      clusters by density functional theory and comparison with experimental
      photoelectron spectroscopy.
AB  - The structural evolution and bonding of a series of early transition-metal
      dioxide clusters, V(n)O(2)(q)(n = 3-9, q = 0, -1), have been investigated using
      density functional theory (DFT) calculations and the results are compared with
      experimental literature data. For each vanadium dioxide cluster, many low-lying
      isomers are generated using the Saunders "Kick" global minimum stochastic search
      method. Theoretical electron detachment energies (both vertical and adiabatic)
      were compared with the experimental measurements to verify the ground states of
      the vanadium dioxide clusters obtained from the DFT calculations. Five kinds of
      dissociative adsorption configurations of ground-state structure of V(n)O(2)(q)
      are identified. The dissociative adsorption of O(2) on V(n)(-1, 0) is more
      favorable than O(2) molecular adsorption. Furthermore, the adsorption energy of
      O(2) is higher than that of a single atom on the bare V(n)(-1, 0) clusters, but
      less than twice the adsorption energy for an atom, indicating that O(2) being
      adsorbed on vanadium clusters are more difficult than single O atom adsorbed on
      vanadium clusters.

PMID- 23126708
TI  - Accurate potential energy curves for HeH+ isotopologues.
AB  - New accurate ground-state potential energy curves (PEC) for the (4)HeH(+),
      (4)HeD(+), (3)HeH(+), and (3)HeD(+) isotopologues are calculated with 600
      explicitly correlated Gaussian (ECG) functions with shifted centers in the range
      between R = 0.35 a(0) and 145 a(0). The calculations include the adiabatic
      corrections (AC). The absolute accuracy of all Born-Oppenheimer (BO) PEC points
      is better than 0.0018 cm(-1) and it is better than 0.0005 cm(-1) for the ACs.
      With respect to the very recent BO PEC calculations performed by Pachucki with 20
      000 generalized Heitler-London explicitly correlated functions [K. Pachucki,
      Phys. Rev. A 85, 042511 (2012)], the present energy calculated at R = 1.46 a(0)
      (a point near the BO equilibrium distance) lies above by only 0.0012 cm(-1).
      Using Pachucki's BO energy at the equilibrium distance of R = 1.463 283 a(0), and
      the adiabatic corrections calculated in this work for the (4)HeH(+), (4)HeD(+),
      (3)HeH(+), and (3)HeD(+) isotopologues, the following values are obtained for
      their PEC depths: 16 448.99893 cm(-1), 16 456.86246 cm(-1), 16 451.50635 cm(-1),
      and 16 459.36988 cm(-1), respectively. We also calculate the rovibrational
      (rovib) frequencies for the four isotopologues using the BO PEC of Pachucki
      augmented with the present ACs. The improvements over the BO+AC PEC of Bishop and
      Cheung (BC) [J. Mol. Spectrosc. 75, 462 (1979)] are 1.522 cm(-1) at R = 4.5 a(0)
      and 0.322 cm(-1) at R = infinity. To partially account for the nonadiabatic
      effects in the rovib calculations an effective reduced-mass approach is used.
      With that, the present (4)HeH(+) rovibrational transitions are considerably
      improved over the BC transitions as compared with the experimental values. Now
      the rovibrational transitions near the dissociation limit are as well reproduced
      by the present calculations as the lower transitions. For example, for the
      (4)HeD(+) transitions corresponding to the nu = 13-9 hot bands the results are
      off from the experimental values by less than 0.023 cm(-1). This confirms high
      accuracy of the present PECs at larger internuclear separations.

PMID- 23126709
TI  - Electron attachment to 14 halogenated alkenes and alkanes, 300-600 K.
AB  - Thermal electron attachment to 14 alkenes and alkanes with bromine, fluorine, and
      iodine substituents has been studied over the temperature range 300-600 K using a
      flowing-afterglow Langmuir-probe apparatus. Rate coefficients and anion products
      are reported, most for the first time. Among these were 3 isomers of C(3)F(5)Br
      and the 2 isomers of C(3)F(7)I. Four dibromide compounds were studied, all of
      which yield Br(2)(-) product in addition to Br(-) product. The results are
      analyzed using a statistical kinetic modeling approach, which is able to
      reproduce both attachment rate coefficients and product branching ratios within
      experimental uncertainty. The kinetic modeling indicates that factor of 2
      differences in attachment rate coefficients to the isomeric species can be
      explained by subtle variations in the potential surfaces.

PMID- 23126710
TI  - Dynamics of the reactions of O(1D) with CD3OH and CH3OD studied with time
      resolved Fourier-transform IR spectroscopy.
AB  - We investigated the reactivity of O((1)D) towards two types of hydrogen atoms in
      CH(3)OH. The reaction was initiated on irradiation of a flowing mixture of O(3)
      and CD(3)OH or CH(3)OD at 248 nm. Relative vibration-rotational populations of OH
      and OD (1 <= v <= 4) states were determined from their infrared emission recorded
      with a step-scan time-resolved Fourier-transform spectrometer. In O((1)D) +
      CD(3)OH, the rotational distribution of OD is nearly Boltzmann, whereas that of
      OH is bimodal; the product ratio [OH]/[OD] is 1.56 +/- 0.36. In O((1)D) +
      CH(3)OD, the rotational distribution of OH is nearly Boltzmann, whereas that of
      OD is bimodal; the product ratio [OH]/[OD] is 0.59 +/- 0.14. Quantum-chemical
      calculations of the potential energy and microcanonical rate coefficients of
      various channels indicate that the abstraction channels are unimportant and
      O((1)D) inserts into the C-H and O-H bonds of CH(3)OH to form HOCH(2)OH and
      CH(3)OOH, respectively. The observed three channels of OH are consistent with
      those produced via decomposition of the newly formed OH or the original OH moiety
      in HOCH(2)OH or decomposition of CH(3)OOH. The former decomposition channel of
      HOCH(2)OH produces vibrationally more excited OH because of incomplete
      intramolecular vibrational relaxation, and decomposition of CH(3)COOH produces OH
      with greater rotational excitation, likely due to a large torque angle during
      dissociation. The predicted [OH]/[OD] ratios are 1.31 and 0.61 for O((1)D) +
      CD(3)OH and CH(3)OD, respectively, at collision energy of 26 kJ mol(-1), in
      satisfactory agreement with the experimental results. These predicted product
      ratios vary weakly with collision energy.

PMID- 23126711
TI  - Thermal decomposition of CH3CHO studied by matrix infrared spectroscopy and
      photoionization mass spectroscopy.
AB  - A heated SiC microtubular reactor has been used to decompose acetaldehyde and its
      isotopomers (CH(3)CDO, CD(3)CHO, and CD(3)CDO). The pyrolysis experiments are
      carried out by passing a dilute mixture of acetaldehyde (roughly 0.1%-1%)
      entrained in a stream of a buffer gas (either He or Ar) through a heated SiC
      reactor that is 2-3 cm long and 1 mm in diameter. Typical pressures in the
      reactor are 50-200 Torr with the SiC tube wall temperature in the range 1200-1900
      K. Characteristic residence times in the reactor are 50-200 MUs after which the
      gas mixture emerges as a skimmed molecular beam at a pressure of approximately 10
      MUTorr. The reactor has been modified so that both pulsed and continuous modes
      can be studied, and results from both flow regimes are presented. Using various
      detection methods (Fourier transform infrared spectroscopy and both fixed
      wavelength and tunable synchrotron radiation photoionization mass spectrometry),
      a number of products formed at early pyrolysis times (roughly 100-200 MUs) are
      identified: H, H(2), CH(3), CO, CH(2)=CHOH, HC=CH, H(2)O, and CH(2)=C=O; trace
      quantities of other species are also observed in some of the experiments.
      Pyrolysis of rare isotopomers of acetaldehyde produces characteristic isotopic
      signatures in the reaction products, which offers insight into reaction
      mechanisms that occur in the reactor. In particular, while the principal
      unimolecular processes appear to be radical decomposition CH(3)CHO (+M) -> CH(3)
      + H + CO and isomerization of acetaldehyde to vinyl alcohol, it appears that the
      CH(2)CO and HCCH are formed (perhaps exclusively) by bimolecular reactions,
      especially those involving hydrogen atom attacks.

PMID- 23126712
TI  - Structures and magnetism of multinuclear vanadium-pentacene sandwich clusters and
      their 1D molecular wires.
AB  - Two types of multinuclear sandwich clusters, (V(3))(n)Pen(n+1), (V(4))(n)Pen(n+1)
      (Pen = Pentacene; n = 1, 2), and their corresponding infinite one-dimensional
      (1D) molecular wires ([V(3)Pen](infinity), [V(4)Pen](infinity)) are investigated
      theoretically, especially on their magnetic coupling mechanism. These sandwich
      clusters and molecular wires are found to be of high stability and exhibit
      intriguing magnetic properties. The intra-layered V atoms in (V(3))(n)Pen(n+1)
      clusters prefer antiferromagnetic (AFM) coupling, while they can be either
      ferromagnetic (FM) or AFM coupling in (V(4))(n)Pen(n+1) depending on the intra
      layered V-V distances via direct exchange or superexchange mechanism. The inter
      layered V atoms favor FM coupling in (V(3))(2)Pen(3), whereas they are AFM
      coupled in (V(4))(2)Pen(3). Such magnetic behaviors are the consequence of the
      competition between direct exchange and superexchange interactions among inter
      layered V atoms. In contrast, the 1D molecular wires, [V(3)Pen](infinity) and
      [V(4)Pen](infinity), appear to be FM metallic with ultra high magnetic moments of
      6.8 and 4.0 MU(B) per unit cell respectively, suggesting that they can be served
      as good candidates for molecular magnets.

PMID- 23126713
TI  - Raman spectroscopy and crystal-field split rotational states of photoproducts CO
      and H2 after dissociation of formaldehyde in solid argon.
AB  - Raman signal is monitored after 248 nm photodissociation of formaldehyde in solid
      Ar at temperatures of 9-30 K. Rotational transitions J = 2 <- 0 for para-H(2)
      fragments and J = 3 <- 1 for ortho-H(2) are observed as sharp peaks at 347.2 cm(
      1) and 578.3 cm(-1), respectively, which both are accompanied by a broader
      shoulder band that shows a split structure. The rovibrational spectrum of CO
      fragments has transitions at 2136.5 cm(-1), 2138.3 cm(-1), 2139.9 cm(-1), and
      2149 cm(-1). To explain the observations, we performed adiabatic rotational
      potential calculations to simulate the Raman spectrum. The simulations indicate
      that the splitting of rotational transitions is a site effect, where H(2)
      molecules can reside in a substitution site, in addition to an interstitial site.
      In the former site, rotational motion is unperturbed by the electrostatic field
      of the host atoms, while the latter site splits the excited rotational manifolds,
      J = 2 and 3, into doublet and triplet structures, respectively. For CO, the
      spectrum can be ascribed to monomeric species in single- and double-substitution
      sites, to a dimeric species (CO)(2), and to a CO-H(2)O complex. The simulations
      show that a nearest-neighbor molecular complex CO-H(2) is not responsible for any
      of the observed spectral fingerprints. The cause of the exit of the molecular
      hydrogen from the initial cage can be traced to high translational energy of the
      fragment after the photodissociation. After the matrix has reached a thermal
      equilibrium, a diffusion driven formation of the complex is possibly hindered by
      the high rotational zero-point energy developed upon complexation.

PMID- 23126714
TI  - Quantum spin transport through magnetic superatom dimer (Cs8V-Cs8V).
AB  - Theoretical studies of the spin transport through a magnetic superatom dimer
      (Cs(8)V)-(Cs(8)V) have been carried out within a density functional theory
      combined with nonequilibrium Green's-function formalism. It is shown that the
      electronic transport is sensitive to the binding site as well as the contact
      distance between the dimer and the electrode, and that the conductance at zero
      bias exhibits an oscillatory behavior as a function of the contact distance. The
      conductance in ferromagnetic state shows an unusually high spin polarization that
      exceeds 80% at large separations. The I-V curve shows negative differential
      resistance for specific contact distances, whose origin lies in the shift of
      frontier energy levels as well as the charged state of the superatom, under
      external bias.

PMID- 23126715
TI  - Theoretical study of Au(n)V-CO, n = 1-14: the dopant vanadium enhances CO
      adsorption on gold clusters.
AB  - The CO adsorption on vanadium-doped gold clusters Au(n)V with n = 1-14 is studied
      by density functional theory computations, using the BB95 and B3LYP functionals
      along with the cc-pVDZ-PP basis for metals and cc-pVTZ for non-metals. When both
      Au and V sites are exposed, CO adsorption on V is thermodynamically favorable
      because with partially filling d orbitals vanadium is more willing to interact
      with CO empty or filled orbitals. When vanadium is confined inside a gold cage,
      the low-coordinated Au atoms become the preferred sites for CO attachment. The
      presence of V tends to reinforce CO adsorption as compared with the bare gold
      clusters. The diatomic AuV is predicted to have the largest CO adsorption
      affinity as it has a typical pi-back donation bond. Au(n)V-CO complexes typically
      have the larger CO binding energies and larger CO frequency shift than the
      isoatomic gold-carbonyl Au(n+1)-CO counterparts.

PMID- 23126716
TI  - Properties of atoms under pressure: bonded interactions of the atoms in three
      perovskites.
AB  - The crystal structures for the three perovskites, CaSnO(3), YAlO(3), and
      LaAlO(3), were geometry optimized at the density functional theory level for a
      wide range of simulated isotropic pressures up to 80 GPa. The connections between
      the geometry optimized bond lengths, R(M-O), the values of the electron density,
      rho(r(c)), the local kinetic, G(r(c)), potential, V(r(c)), energy densities,
      H(r(c)), and the Laplacian, ?(2)(r(c)), at the bond critical points, r(c), for
      the M-O nonequivalent bonded interactions were examined. With increasing
      pressure, rho(r(c)) increases along four distinct trends when plotted in terms of
      the Al-O, Ca-O, Sn-O, Y-O, and La-O bond lengths, but when the bond lengths were
      plotted in terms of rho(r(c))/r where r is the periodic table row number of the M
      atoms, the data scatter along a single trend modeled by the power law regression
      expression R(M-O) = 1.41(rho(r(c))/r)(-0.21), an expression that is comparable
      with that obtained for the bonded interactions for a large number of silicate and
      oxides crystals, R(M-O) = 1.46(rho(r(c))/r)(-0.19) and that obtained for a
      relatively large number of hydroxyacid molecules R(M-O) = 1.39(s/r)(-0.22) where
      s is the Pauling bond strength of a bonded interaction. The similarity of the
      expressions determined for the perovskites, silicate and oxides crystals, and
      hydroxyacid molecules suggest that the bonded interactions in molecules and
      crystal are not only similar and comparable. The close correspondence of the
      expressions for the perovskites, the silicate and oxide crystals, and the
      molecules indicates that Pauling bond strength and rho(r(c)) are comparable
      measures of the bonded interactions, the larger the accumulation of the electron
      density between the bonded atoms the larger the value of s, the shorter the bond
      lengths. It also indicates that the bonded interactions that govern the bond
      length variations behave as if largely short ranged. Like rho(r(c))/r, the values
      of G(r(c))/r, V(r(c))/r, ?(2)(r(c))/r likewise correlate in terms of R(M-O) in a
      single trend. With increasing pressure, the value of V(r(c)) decreases at a
      faster rate than G(r(c)) increases consistent with the observation that rho(r(c))
      increases with increasing pressure thereby stabilizing the structures at high
      pressures. As evinced by the well-developed power law trends between R(M-O) and
      the bond critical point properties, the bulk of the bonded interactions for the
      perovskites are concluded to change progressively from closed-shell to
      intermediate polar covalent interactions with increasing pressure. A well
      developed trend between the ratios ?V(r(c))? /G(r(c)) and H(r(c))/rho(r(c)) is
      consistent with this conclusion. The employment of a positive value for the
      Laplacian alone in distinguishing between closed shell and polar covalent bonded
      interactions is unsatisfactory when 2G(r(c)) > ?V(r(c))? > G(r(c)).

PMID- 23126717
TI  - Rate coefficients from quantum and quasi-classical cumulative reaction
      probabilities for the S(1D) + H2 reaction.
AB  - Cumulative reaction probabilities (CRPs) at various total angular momenta have
      been calculated for the barrierless reaction S((1)D) + H(2) -> SH + H at total
      energies up to 1.2 eV using three different theoretical approaches: time
      independent quantum mechanics (QM), quasiclassical trajectories (QCT), and
      statistical quasiclassical trajectories (SQCT). The calculations have been
      carried out on the widely used potential energy surface (PES) by Ho et al. [J.
      Chem. Phys. 116, 4124 (2002)] as well as on the recent PES developed by Song et
      al. [J. Phys. Chem. A 113, 9213 (2009)]. The results show that the differences
      between these two PES are relatively minor and mostly related to the different
      topologies of the well. In addition, the agreement between the three theoretical
      methodologies is good, even for the highest total angular momenta and energies.
      In particular, the good accordance between the CRPs obtained with dynamical
      methods (QM and QCT) and the statistical model (SQCT) indicates that the reaction
      can be considered statistical in the whole range of energies in contrast with the
      findings for other prototypical barrierless reactions. In addition, total CRPs
      and rate coefficients in the range of 20-1000 K have been calculated using the
      QCT and SQCT methods and have been found somewhat smaller than the experimental
      total removal rates of S((1)D).

PMID- 23126718
TI  - Oxalyl chloride, ClC(O)C(O)Cl: UV/vis spectrum and Cl atom photolysis quantum
      yields at 193, 248, and 351 nm.
AB  - Oxalyl chloride, (ClCO)(2), has been used as a Cl atom photolytic precursor in
      numerous laboratory kinetic and photochemical studies. In this study, the UV/vis
      absorption spectrum of (ClCO)(2) and the Cl atom quantum yields in its photolysis
      at 193, 248, and 351 nm are reported. The UV/vis spectrum was measured between
      200 and 450 nm at 296 K using diode array spectroscopy in conjunction with an
      absolute cross section obtained at 213.9 nm. Our results are in agreement with
      the spectrum reported by Baklanov and Krasnoperov [J. Phys. Chem. A 105, 97-103
      (2001)], which was obtained at 11 discrete wavelengths between 193.3 and 390 nm.
      Cl atom quantum yields, Phi(lambda), were measured using pulsed laser photolysis
      coupled with time resolved atomic resonance fluorescence detection of Cl. The UV
      photolysis of (ClCO)(2) has been shown in previous studies to occur via an
      impulsive three-body dissociation mechanism, (COCl)(2) + hv -> ClCO* + Cl + CO
      (2), where the excited ClCO radical, ClCO*, either dissociates or stabilizes
      ClCO* -> Cl + CO (3a), -> ClCO (3b). ClCO is thermally unstable at the
      temperatures (253-298 K) and total pressures (13-128 Torr) used in our
      experiments ClCO + M -> Cl + CO + M (4) leading to the formation of a secondary
      Cl atom that was resolvable in the Cl atom temporal profiles obtained in the 248
      and 351 nm photolysis of (ClCO)(2). Phi(193 nm) was found to be 2.07 +/- 0.37
      independent of bath gas pressure (25.8-105.7 Torr, N(2)), i.e., the branching
      ratio for channel 2a or the direct formation of 2Cl + 2CO in the photolysis of
      (ClCO)(2) is >0.95. At 248 nm, the branching ratio for channel 2a was determined
      to be 0.79 +/- 0.15, while the total Cl atom yield, i.e., following the
      completion of reaction (4), was found to be 1.98 +/- 0.26 independent of bath gas
      pressure (15-70 Torr, N(2)). Phi(351 nm) was found to be pressure dependent
      between 7.8 and 122.4 Torr (He, N(2)). The low-pressure limit of the total Cl
      atom quantum yield, Phi(0)(351 nm), was 2.05 +/- 0.24. As part of this work, rate
      coefficients for the thermal decomposition of ClCO were measured between 253 and
      298 K at total pressures between 13 and 128 Torr (He and N(2) bath gases). The
      N(2) bath gas results were combined with the data reported in Nicovich et al. [J.
      Chem. Phys. 92, 3539-3544 (1990)] to yield k(4)(T, N(2)) = (4.7 +/- 0.7) * 10(
      10) exp [-(2987 +/- 16)/T] cm(3) molecule(-1) s(-1), while the He bath gas data
      fit yielded k(4)(T, He) = (2.3 +/- 2.1) * 10(-10) exp [-(2886 +/- 218)/T] cm(3)
      molecule(-1) s(-1). The quoted uncertainties are at the 2sigma level from the
      precision of the fit. In addition, the room temperature rate coefficient for the
      Cl + ClNO reaction was measured in this work to be (1.03 +/- 0.10) * 10(-10)
      cm(3) molecule(-1) s(-1).

PMID- 23126719
TI  - Core-mass nonadiabatic corrections to molecules: H2, H2+, and isotopologues.
AB  - For high-precision calculations of rovibrational states of light molecules, it is
      essential to include non-adiabatic corrections. In the absence of crossings of
      potential energy surfaces, they can be incorporated in a single surface picture
      through coordinate-dependent vibrational and rotational reduced masses. We
      present a compact method for their evaluation and relate in particular the
      vibrational mass to a well defined nuclear core mass derived from a Mulliken
      analysis of the electronic density. For the rotational mass we propose a simple,
      but very effective parametrization. The use of these masses in the nuclear
      Schrodinger equation yields numerical data for the corrections of a much higher
      quality than can be obtained with optimized constant masses, typically better
      than 0.1 cm(-1). We demonstrate the method for H(2), H(2)(+), and singly
      deuterated isotopologues. Isotopic asymmetry does not present any particular
      difficulty. Generalization to polyatomic molecules is straightforward.

PMID- 23126721
TI  - Theoretical study of the predissociation of the A2Pi state of ZnF including quasi
      diabatisation of the spin-orbit coupling.
AB  - The excited (2)Pi electronic states of ZnF have been diabatized in order to
      simulate the (2)Pi <- X(2)Sigma(+) vibronic spectrum using a wavepacket
      propagation technique. The spin-orbit coupling functions within the (2)Pi states
      and between the (2)Pi and B(2)Sigma(+) states have also been diabatized, as well
      as the dipole and transition moment functions. As the adiabatic electronic (2)Pi
      states are strongly multi-configurational, the quasi-diabatisation scheme was
      based on the electronic wavefunction overlap along the reaction coordinate. The
      procedure leads to a repulsive (2)Pi state reaching the first dissociation limit,
      Zn((1)S(g)) + F((2)P(u)), and a bound one associated with the second limit,
      Zn((3)P(u)) + F((2)P(u)). The adiabatic electronic potentials and coupling
      functions have been determined at the multi-reference-configuration-interaction
      level of theory. The vibrational energies and the spin-orbit splittings are in
      agreement with early experimental data. The wavepacket propagation approach,
      coupled with a Prony analysis, allowed also to analyze the resonances and the
      bound vibronic states of the (2)Pi manifold. The (2)Pi <- X(2)Sigma(+) vibronic
      spectra have been determined for Omega = 1/2 and 3/2 originating to the v'' = 0
      level of the X(2)Sigma(+) state.

PMID- 23126720
TI  - Excited state properties of formamide in water solution: an ab initio study.
AB  - We present ab initio quantum calculation of the optical properties of formamide
      in vapor phase and in water solution. We employ time dependent density functional
      theory for the isolated molecule and many-body perturbation theory methods for
      the system in solution. An average over several molecular dynamics snapshots is
      performed to take into account the disorder of the liquid. We find that the
      excited state properties of the gas-phase formamide are strongly modified by the
      presence of the water solvent: the geometry of the molecule is distorted and the
      electronic and optical properties are severely modified. The important
      interaction among the formamide and the water molecules forces us to use fully
      quantum methods for the calculation of the excited state properties of this
      system. The excitonic wave function is localized both on the solute and on part
      of the solvent.

PMID- 23126722
TI  - A two-state model of twisted intramolecular charge-transfer in monomethine dyes.
AB  - A two-state model Hamiltonian is proposed, which can describe the coupling of
      twisting displacements to charge-transfer behavior in the ground and excited
      states of a general monomethine dye molecule. This coupling may be relevant to
      the molecular mechanism of environment-dependent fluorescence yield enhancement.
      The model is parameterized against quantum chemical calculations on different
      protonation states of the green fluorescent protein chromophore, which are chosen
      to sample different regimes of detuning from the cyanine (resonant) limit. The
      model provides a simple yet realistic description of the charge transfer
      character along two possible excited state twisting channels associated with the
      methine bridge. It describes qualitatively different behavior in three regions
      that can be classified by their relationship to the resonant (cyanine) limit. The
      regimes differ by the presence or absence of twist-dependent polarization
      reversal and the occurrence of conical intersections. We find that selective
      biasing of one twisting channel over another by an applied diabatic biasing
      potential can only be achieved in a finite range of parameters near the cyanine
      limit.

PMID- 23126723
TI  - High pressure synthesis and in situ Raman spectroscopy of H2 and HD clathrate
      hydrates.
AB  - By means of a newly constructed high pressure and low temperature optical
      apparatus we have measured the Raman spectra of H(2) and HD simple clathrate
      hydrates, synthesized in situ by the application of more than 2500 bar gas
      pressure on solid water. High resolution spectra of the molecular vibration have
      been measured at low temperature (about 20 K). In the case of HD this band is
      simpler than in the case of H(2), where the presence of the ortho- and para
      species complicated the interpretation of the spectrum. We have determined
      frequency positions of the bands arising from multiple occupancy of the large
      cages of the sII clathrate, some of which are almost superimposed. The intensity
      of the bands gives information on the average and distribution of cage
      occupation, and of the ortho-para (o-p) ratio of H(2) molecules. Hydrogen o-p
      conversion rate is measured, for molecules in the small cages and in the large
      cages, and it is observed that these are different. A model considering both
      intrinsic and extrinsic conversion processes is applied to the measured data. The
      intrinsic conversion rate so derived is compared favorably to that measured for
      pure hydrogen in different situations.

PMID- 23126724
TI  - Varying the charge of small cations in liquid water: structural, transport, and
      thermodynamical properties.
AB  - In this work, we show how increasing the charge of small cations affects the
      structural, thermodynamical, and dynamical properties of these ions in liquid
      water. We have studied the case of lanthanoid and actinoid ions, for which we
      have recently developed accurate polarizable force fields, and the ionic radius
      is in the 0.995-1.250 A range, and explored the valency range from 0 to 4+. We
      found that the ion charge strongly structures the neighboring water molecules and
      that, in this range of charges, the hydration enthalpies exhibit a quadratic
      dependence with respect to the charge, in line with the Born model. The diffusion
      process follows two main regimes: a hydrodynamical regime for neutral or low
      charges, and a dielectric friction regime for high charges in which the
      contraction of the ionic radius along the series of elements causes a decrease of
      the diffusion coefficient. This latter behavior can be qualitatively described by
      theoretical models, such as the Zwanzig and the solvated ion models. However,
      these models need be modified in order to obtain agreement with the observed
      behavior in the full charge range. We have thus modified the solvated ion model
      by introducing a dependence of the bare ion radius as a function of the ionic
      charge. Besides agreement between theory and simulation this modification allows
      one to obtain an empirical unified model. Thus, by analyzing the contributions to
      the drag coefficient from the viscous and the dielectric terms, we are able to
      explain the transition from a regime in which the effect of viscosity dominates
      to one in which dielectric friction governs the motion of ions with radii of ca.
      1 A.

PMID- 23126725
TI  - Ultrafast excited-state dynamics associated with the photoisomerization of a
      cyanine dye.
AB  - The ultrafast excited-state dynamics of a cyanine dye, 3,3'-bis(3-sulfopropyl)
      5,5'-dimethoxy-thiacyanine triethylaminium salt, was investigated by using
      conventional time-resolved fluorescence up-conversion technique. The fluorescence
      decay can be well described as tri-exponential kinetics, which indicates the
      excited-state population decays through the bond-twist, vibrational and radiative
      relaxation channels. Further analysis shows that the contributions of the three
      relaxation channels to the fluorescence decay demonstrate very different change
      with increasing the fluorescence wavelength, through which the detailed dynamics
      at different regions in the excited-state potential energy surface can be
      retrieved.

PMID- 23126726
TI  - Mode coupling and fragile to strong transition in supercooled TIP4P water.
AB  - We consider one of the most used model for water, the rigid four site TIP4P
      potential, and we study by molecular dynamics simulation the dynamical properties
      of the liquid upon supercooling. In the previous studies of the thermodynamics of
      the TIP4P model a liquid-liquid critical point (LLCP) located at the end of the
      coexistence between the low density liquid (LDL) and the high density liquid
      (HDL) of water was found. We present here the analysis of the self intermediate
      scattering functions in a large range of temperatures and densities and we show
      that the structural relaxation in the region of mild supercooling is in agreement
      with the predictions of the mode coupling theory. In the more deep supercooled
      region we observe that the alpha-relaxation time deviates from the mode coupling
      theory (MCT) trend and a crossover takes place from a fragile to a strong
      behavior upon crossing the Widom line emanating from the LLCP. The HDL and the
      LDL phases are associated with the fragile and the strong behavior, respectively.

PMID- 23126727
TI  - Coordination state probabilities and the solvation free energy of Zn2+ in aqueous
      methanol solutions.
AB  - Coordination state probabilities for the [Zn(H(2)O)(n)(CH(3)OH)(m)](2+) complex
      in aqueous methanol solutions are calculated as a function of the bulk solution
      concentration, and the number of methanol ligands, m = 0, 1, ..., 6 with n+m = 6.
      Zinc ion solvation free energies, which serve to normalize these probabilities,
      also reproduce the methanol concentration dependence of the experimentally
      derived free energy of zinc ion transfer from water to aqueous methanol
      solutions. Coordination state probabilities, p(n, m), are derived by extending
      quasi-chemical theory of ion hydration to solvent mixtures and mixed ligands.
      Free energy contributions to p(n, m) include the free energy of forming the mixed
      ligand complex in the ideal gas, obtained by quantum chemical calculations, and
      the solvation free energy of the complex, approximated by a dielectric continuum
      model. We find that replacing water ligands with methanol ligands preferentially
      stabilizes methanol-rich complexes in the ideal gas. Conversely, water-rich
      complexes are stabilized by the solvation free energy contribution, such that the
      [Zn(H(2)O)(6)](2+) complex is the dominant species in solution for all methanol
      concentrations considered. Stabilization of the methanol-rich complexes is a
      consequence of the local coordination chemistry, dominated by the delocalization
      of charge on the zinc ion, while the stabilization of water-rich complexes is a
      consequence of favorable ion-solvent electrostatic interactions and smaller
      dielectric cavities for the water-rich complexes at fixed total charge in the
      dielectric continuum model. Our analysis also highlights an entropic contribution
      associated with the reversible work required to remove n water and m methanol
      molecules from bulk solution to form the [Zn(H(2)O)(n)(CH(3)OH)(m)](2+) complex,
      which captures the methanol concentration dependence of the solvation free energy
      of the zinc ion.

PMID- 23126728
TI  - Entropic vs. elastic models of fragility of glass-forming liquids: two sides of
      the same coin?
AB  - The two most influential atomistic models that have been proposed in the
      literature to explain the temperature dependent activation energy of viscous flow
      of a glass-forming liquid, i.e., its fragility, are the configurational entropy
      model of Adam and Gibbs [J. Chem. Phys. 43, 139 (1965)] and the elastic "shoving"
      model of Dyre et al. [J. Non-Cryst. Solids 352, 4635 (2006)]. Here we demonstrate
      a qualitative equivalence between these two models starting from the well
      established general relationships between the interatomic potentials, elastic
      constants, structural rearrangement, and entropy in amorphous materials. The
      unification of these two models provides important predictions that are
      consistent with experimental observations and shed new light into the problem of
      glass transition.

PMID- 23126729
TI  - Vibrational mode frequencies of H4SiO4, D4SiO4, H6Si2O7, and H6Si3O9 in aqueous
      environment, obtained from ab initio molecular dynamics.
AB  - We report the vibrational properties of H(4)SiO(4), D(4)SiO(4), H(6)Si(2)O(7),
      and H(6)Si(3)O(9) in aqueous solution at 300 K and 1000 K, obtained from the
      combination of ab initio molecular dynamics (MD) and a mode-decomposition
      approach. This combination yields vibrational subspectra for selected vibrational
      modes at finite temperatures. We also performed normal-mode analysis (NMA) on
      numerous configurations from the same MD run to sample the effect of the variable
      molecular environment. We found good agreement between both approaches. The
      strongest effect of temperature is on the SiOH bending mode deltaSiOH, which is
      at about 1145 cm(-1) in solution at 300 K, opposed to about 930 cm(-1) in
      solution at 1000 K. The frequency of the deltaSiOH vibration also depends on
      environment, shifting from 1145 cm(-1) in solution to about 845 cm(-1) in the gas
      phase. We found both in the mode-decomposition approach and in multiple
      configuration NMA that the H(6)Si(2)O(7) dimer shows a vibrational mode at about
      790 cm(-1), which we consider to be responsible for a hitherto unexplained
      shoulder of the monomer Raman band at 770 cm(-1) in dilute silica solutions. Our
      results demonstrate the importance of temperature and solvation environment in
      calculations that aim to support the interpretation of experimental Raman spectra
      of dissolved silica.

PMID- 23126730
TI  - Metastable Lennard-Jones fluids. I. Shear viscosity.
AB  - Molecular dynamics methods have been employed to calculate the coefficient of
      shear viscosity eta(s)* of a Lennard-Jones fluid. Calculations have been
      performed in the range of reduced temperatures 0.4 <= k(B)T/epsilon <= 2.0 and
      densities 0.01 <= rhosigma(3) <= 1.2. Values of eta(s)* have been obtained for
      217 states, 99 of which refer to metastable liquid and gas regions. The results
      of calculating eta(s)* for thermodynamically stable states are in satisfactory
      agreement with the data of earlier investigations. An equation has been obtained
      which describes the temperature and density dependence of the coefficient of
      shear viscosity in stable and metastable regions of the phase diagram up to the
      boundaries of spontaneous nucleation. The behavior of the coefficient of shear
      viscosity close to the spinodal of a superheated liquid and supersaturated vapor
      is discussed and the applicability of the Stokes-Einstein relation at high
      supercoolings of the liquid phase is examined.

PMID- 23126731
TI  - Uranyl ion interaction at the water/NiO(100) interface: a predictive
      investigation by first-principles molecular dynamic simulations.
AB  - The behavior of the UO(2)(2+) uranyl ion at the water/NiO(100) interface was
      investigated for the first time using Born-Oppenheimer molecular dynamic
      simulations with the spin polarized DFT + U extension. A water/NiO(100) interface
      model was first optimized on a defect-free five layers slab thickness, proposed
      as a reliable surface model, with an explicit treatment of the solvent. Water
      molecules are adsorbed with a well-defined structure in a thickness of about 4 A
      above the surface. The first layer, adsorbed on nickel atoms, remains mainly in
      molecular form but can partly dissociate at 293 K. Considering low acidic
      conditions, a bidentate uranyl ion complex was characterized on two surface
      oxygen species (arising from water molecules adsorption on nickel atoms) with d(U
      O(adsorption))=2.39 A. This complex is stable at 293 K due to iono-covalent bonds
      with an estimated charge transfer of 0.58 electron from the surface to the uranyl
      ion.

PMID- 23126732
TI  - Rattler model of the boson peak at silica surfaces.
AB  - Recent experiments unveiled two new aspects of the low-energy excitation spectrum
      of silica glass--commonly termed as the "boson peak" region. The first is that at
      low temperature the silica surface exhibits a different, softer boson peak than
      the bulk. The second is a giant thermal blueshift of the surface boson peak
      frequency causing it to cross and overcome the bulk peak with increasing
      temperature. Here we present a simple lattice model that reproduces this behavior
      in all its aspects. Each site consists of rigid tetrahedral units softly
      connected so as to be able to rotate anharmonically as "rattlers" in their cages.
      As shown by simulations, the model dynamics exhibits a boson-like peak, which has
      lower frequency at the surface where rattlers have a weaker restoring force. Upon
      heating however the larger angular freedom of surface units allows them to rattle
      more than in the bulk, leading to a steeper frequency increase similar to
      experiment.

PMID- 23126733
TI  - A close look into the excluded volume effects within a double layer.
AB  - We explore the effect of steric interaction on the ionic density distribution
      near a charged hard wall. For weakly charged walls, small particles, and
      monovalent ions, the mean-field Poisson-Boltzmann equation provides an excellent
      description of the density profiles. For large ions and large surface charges,
      however, deviations appear. To explore these, we use the density functional
      theory. We find that local density functionals are not able to account for steric
      interactions near a wall. Based on the weighted density approximation, we derive
      a simple analytical expression for the contact electrostatic potential, which
      allows us to analytically calculate the differential capacitance of the double
      layer.

PMID- 23126734
TI  - Micro-imaging of transient guest profiles in nanoporous host systems of
      cylindrical symmetry.
AB  - Nanoporous host materials giving rise to transient guest profiles of cylindrical
      symmetry during molecular uptake and release are shown to provide particularly
      advantageous conditions for the study of guest diffusion by micro-imaging.
      Considering zeolites of structure type DDR (Deca-dodecasil 3R) as a host system
      and short-chain length hydrocarbons as guest molecules, the benefits thus
      attainable in micro-imaging studies using interference microscopy are shown to
      include the determination of transient concentration profiles with improved
      accuracy, the option to overcome the disturbing impact of surface imperfections,
      and easy access to concentration-dependent diffusivities.

PMID- 23126735
TI  - Local density of states analysis using Bader decomposition for N2 and CO2
      adsorbed on Pt(110)-(1 * 2) electrodes.
AB  - Local density of states and electric charge in regions defined for individual
      atoms and molecules using grid based Bader analysis is presented for N(2) and
      CO(2) adsorbed on a platinum electrode in the presence of an applied electric
      field. When the density of states is projected onto Bader regions, the partial
      density of states for the various subregions correctly sums up to the total
      density of states for the whole system, unlike the commonly used projection onto
      spheres which results in missing contributions from some regions while others are
      over counted, depending on the radius chosen. The electrode is represented by a
      slab with a missing row reconstructed Pt(110)-(1 * 2) surface to model an edge
      between micro-facets on the surface of a nano-particle catalyst. For both N(2)
      and CO(2), a certain electric field window leads to adsorption. The binding of
      N(2) to the electrode is mainly due to polarization of the molecule but for CO(2)
      hybridization occurs between the molecular states and the states of the Pt
      electrode.

PMID- 23126736
TI  - Formation and rupture of capillary bridges in atomic scale friction.
AB  - While formation of capillary bridges significantly contributes to the adhesion
      and friction at micro- and nanoscales, many key aspects of dynamics of capillary
      condensation and its effect on friction forces are still not well understood.
      Here, by analytical model and numerical simulations, we address the origin of
      reduction of friction force with velocity and increase of friction with
      temperature, which have been experimentally observed under humid ambient
      conditions. These observations differ significantly from the results of friction
      experiments carried out under ultrahigh vacuum, and disagree with predictions of
      thermal Prandtl-Tomlinson model of friction. Our calculations demonstrate what
      information on the kinetics of capillary condensation can be extracted from
      measurements of friction forces and suggest optimal conditions for obtaining this
      information.

PMID- 23126737
TI  - A theoretical study of structure and thermodynamics of fluids with long-range
      competing interactions exhibiting pattern formation.
AB  - We study the structure and phase behavior of a model fluid with competing short
      range attraction and long-range repulsion, constituted by hard spheres
      interacting by means of two opposite Kac potentials. We use, to this purpose, a
      thermodynamically self-consistent integral equation approach developed by one of
      the authors [J.-M. Bomont and J.-L. Bretonnet, J. Chem. Phys. 119, 2188 (2003)],
      which proven accurate in predicting the properties of other competing fluids. We
      choose the potential parameters in such a way that, upon appropriate
      thermodynamic conditions, the fluid displays microphase separation terminating,
      at sufficiently low temperatures, with a phase transition into an ordered-pattern
      fluid. The propensity toward the pattern formation is indicated by long
      wavelength, slowly decaying oscillations in the pair correlation function, and by
      the presence of a sharp peak in the structure factor S(q) at a small but finite
      wavevector q(c). The limits of stability of the micro-separated phase are
      identified by a drastic, diverging-like, increase of S(q(c)) as the temperature
      drops. The behavior of S(q) in the disordered-pattern phase suggests that
      different morphologies of the ordered patterns should be expected, depending on
      the ratio between the strengths of competing interactions. The structural
      predictions are confirmed, at the thermodynamic level, by the change of sign
      observed in the "residual multi-particle entropy," according to the one-phase
      ordering criterion developed by Giaquinta and Giunta [Physica A 187, 145 (1992)],
      and by the trend shown by the chemical potential. Our self-consistent approach
      succeeds in describing the thermodynamic regime where the phase transition
      occurs, whereas, as reported in the literature, other sophisticated schemes
      within the same theoretical framework generally fail; reasons of this outcome and
      putative remedies are discussed.

PMID- 23126738
TI  - Collective degrees of freedom involved in absorption and desorption of surfactant
      molecules in spherical non-ionic micelles.
AB  - Dynamics of absorption and desorption of a surfactant monomer into and out of a
      spherical non-ionic micelle is investigated by coarse-grained molecular dynamics
      (MD) simulations. It is shown that these processes involve a complex interplay
      between the micellar structure and the monomer configuration. A quantitative
      model for collective dynamics of these degrees of freedom is developed. This is
      accomplished by reconstructing a multi-dimensional free energy landscape of the
      surfactant-micelle system using constrained MD simulations in which the distance
      between the micellar and monomer centers of mass is held constant. Results of
      this analysis are verified by direct (unconstrained) MD simulations of surfactant
      absorption in the micelle. It is demonstrated that the system dynamics is likely
      to deviate from the minimum energy path on the energy landscape. These deviations
      create an energy barrier for the monomer absorption and increase an existing
      barrier for the monomer desorption. A reduced Fokker-Planck equation is proposed
      to model these effects.

PMID- 23126739
TI  - Solvated dissipative electro-elastic network model of hydrated proteins.
AB  - Elastic network models coarse grain proteins into a network of residue beads
      connected by springs. We add dissipative dynamics to this mechanical system by
      applying overdamped Langevin equations of motion to normal-mode vibrations of the
      network. In addition, the network is made heterogeneous and softened at the
      protein surface by accounting for hydration of the ionized residues. Solvation
      changes the network Hessian in two ways. Diagonal solvation terms soften the
      spring constants and off-diagonal dipole-dipole terms correlate displacements of
      the ionized residues. The model is used to formulate the response functions of
      the electrostatic potential and electric field appearing in theories of redox
      reactions and spectroscopy. We also formulate the dielectric response of the
      protein and find that solvation of the surface ionized residues leads to a slow
      relaxation peak in the dielectric loss spectrum, about two orders of magnitude
      slower than the main peak of protein relaxation. Finally, the solvated network is
      used to formulate the allosteric response of the protein to ion binding. The
      global thermodynamics of ion binding is not strongly affected by the network
      solvation, but it dramatically enhances conformational changes in response to
      placing a charge at the active site of the protein.

PMID- 23126740
TI  - Peptide kinetics from picoseconds to microseconds using boxed molecular dynamics:
      power law rate coefficients in cyclisation reactions.
AB  - Molecular dynamics (MD) methods are increasingly widespread, but simulation of
      rare events in complex molecular systems remains a challenge. We recently
      introduced the boxed molecular dynamics (BXD) method, which accelerates rare
      events, and simultaneously provides both kinetic and thermodynamic information.
      We illustrate how the BXD method may be used to obtain high-resolution kinetic
      data from explicit MD simulations, spanning picoseconds to microseconds. The
      method is applied to investigate the loop formation dynamics and kinetics of
      cyclisation for a range of polypeptides, and recovers a power law dependence of
      the instantaneous rate coefficient over six orders of magnitude in time, in good
      agreement with experimental observations. Analysis of our BXD results shows that
      this power law behaviour arises when there is a broad and nearly uniform spectrum
      of reaction rate coefficients. For the systems investigated in this work, where
      the free energy surfaces have relatively small barriers, the kinetics is very
      sensitive to the initial conditions: strongly non-equilibrium conditions give
      rise to power law kinetics, while equilibrium initial conditions result in a rate
      coefficient with only a weak dependence on time. These results suggest that BXD
      may offer us a powerful and general algorithm for describing kinetics and
      thermodynamics in chemical and biochemical systems.

PMID- 23126741
TI  - Coherent versus incoherent excitation energy transfer in molecular systems.
AB  - We investigate the Markovian limit of a polaronic quantum master equation for
      coherent resonance energy transfer proposed recently by Jang et al. [J. Chem.
      Phys. 129, 101104 (2008)]. An expression for the rate of excitation energy
      transfer (EET) is derived and shown to exhibit both coherent and incoherent
      contributions. We then apply this theory to calculated EET rates for model dimer
      systems, and demonstrate that the small-polaron approach predicts a variety of
      dynamical behaviors. Notably, the results indicate that the EET dynamical
      behaviors can be understood by the interplay between noise-assisted EET and
      dynamical localization, while both are well captured by the polaron theory.
      Finally, we investigate bath correlation effects on the rate of EET and show that
      bath correlations (or anti-correlations) can either enhance or suppress EET rate
      depending on the strength of individual system-bath couplings. In summary, we
      introduce the small-polaron approach as an intuitive physical framework to
      consolidate our understanding of EET dynamics in the condensed phase.

PMID- 23126742
TI  - Note: Effective diffusion coefficient in heterogeneous media.

PMID- 23126744
TI  - Invited article: Relation between electric and magnetic field structures and
      their proton-beam images.
AB  - Proton imaging is commonly used to reveal the electric and magnetic fields that
      are found in high energy density plasmas. Presented here is an analysis of this
      technique that is directed towards developing additional insight into the
      underlying physics. This approach considers: formation of images in the limits of
      weak and strong intensity variations; caustic formation and structure; image
      inversion to obtain line-integrated field characteristics; direct relations
      between images and electric or magnetic field structures in a plasma; imaging of
      sharp features such as Debye sheaths and shocks. Limitations on spatial and
      temporal resolution are assessed, and similarities with optical shadowgraphy are
      noted. Synthetic proton images are presented to illustrate the analysis. These
      results will be useful for quantitatively analyzing experimental proton imaging
      data and verifying numerical codes.

PMID- 23126745
TI  - A compact and efficient strontium oven for laser-cooling experiments.
AB  - Here we describe a compact and efficient strontium oven well suited for laser
      cooling experiments. Novel design solutions allowed us to produce a collimated
      strontium atomic beam with a flux of 1.0 * 10(13) s(-1) cm(-2) at the oven
      temperature of 450  degrees C, reached with an electrical power consumption of 36
      W. The oven is based on a stainless-steel reservoir, filled with 6 g of metallic
      strontium, electrically heated in a vacuum environment by a tantalum wire
      threaded through an alumina multi-bore tube. The oven can be hosted in a standard
      DN40CF cube and has an estimated continuous operation lifetime of 10 years. This
      oven can be used for other alkali and alkaline earth metals with essentially no
      modifications.

PMID- 23126746
TI  - A high resolution ultraviolet Brillouin scattering set-up.
AB  - We report on a high resolution inelastic UV scattering table-top setup conceived
      for Brillouin measurements. The system is based on a tandem 1+1 pass scanning
      Fabry-Perot interferometer of Sandercock type. Special optics were used in order
      to adapt such an interferometric device, nowadays only used at visible or IR
      wavelength, to the UV range. The advantages with respect to other UV Brillouin
      scattering instruments are the larger resolving power and the improved contrast
      in the low frequency spectral region. To corroborate these features we provide a
      comparison between data obtained using the described system and those from
      existing UV Brillouin scattering instruments.

PMID- 23126747
TI  - Simple and versatile heterodyne whole-field interferometer for phase optics
      characterization.
AB  - A wavefront sensor for thermally induced lens and passive lens characterization
      based on low-coherence digital speckle interferometry was developed and studied.
      By illuminating the optical setup with two slightly detuned red diode lasers,
      whole-field contour interference fringes were generated according to the
      resulting synthetic wavelength. For fringe pattern visualization the optical
      setup used the light transmitted through a ground glass plate as object beam. The
      performance of the sensor was investigated and its versatility was demonstrated
      by measuring the thermal lens induced in an Er-doped glass sample pumped by a
      1.76-W diode laser emitting at 976 nm and by evaluating the wavefront distortion
      introduced by an ophthalmic progressive lens.

PMID- 23126748
TI  - In situ triaxial magnetic field compensation for the spin-exchange-relaxation
      free atomic magnetometer.
AB  - The spin-exchange-relaxation-free (SERF) atomic magnetometer is an ultra-high
      sensitivity magnetometer, but it must be operated in a magnetic field with
      strength less than about 10 nT. Magnetic field compensation is an effective way
      to shield the magnetic field, and this paper demonstrates an in situ triaxial
      magnetic field compensation system for operating the SERF atomic magnetometer.
      The proposed hardware is based on optical pumping, which uses some part of the
      SERF atomic magnetometer itself, and the compensation method is implemented by
      analyzing the dynamics of the atomic spin. The experimental setup for this
      compensation system is described, and with this configuration, a residual
      magnetic field of strength less than 2 nT (+/-0.38 nT in the x axis, +/-0.43 nT
      in the y axis, and +/-1.62 nT in the z axis) has been achieved after
      compensation. The SERF atomic magnetometer was then used to verify that the
      residual triaxial magnetic fields were coincident with what were achieved by the
      compensation system.

PMID- 23126749
TI  - A von Hamos x-ray spectrometer based on a segmented-type diffraction crystal for
      single-shot x-ray emission spectroscopy and time-resolved resonant inelastic x
      ray scattering studies.
AB  - We report on the design and performance of a wavelength-dispersive type
      spectrometer based on the von Hamos geometry. The spectrometer is equipped with a
      segmented-type crystal for x-ray diffraction and provides an energy resolution in
      the order of 0.25 eV and 1 eV over an energy range of 8000 eV-9600 eV. The use of
      a segmented crystal results in a simple and straightforward crystal preparation
      that allows to preserve the spectrometer resolution and spectrometer efficiency.
      Application of the spectrometer for time-resolved resonant inelastic x-ray
      scattering and single-shot x-ray emission spectroscopy is demonstrated.

PMID- 23126750
TI  - Practical axial optical trapping.
AB  - We describe a new method for calibrating optical trapping measurements in which
      tension is applied in the direction of the laser beam to a molecule tethered
      between a surface and an optically trapped bead. Specifically, we present a
      generally-applicable procedure for converting from the measured scattering
      intensity and the measured stage displacement to applied tension and bead
      coverslip separation, using measurements of the light intensity scattered from an
      untethered, trapped bead. Our calibration accounts for a number of effects,
      including aberrations and the interference of forward-reflected bead-scattered
      light with the trapping beam. To demonstrate the accuracy of our method, we show
      measurements of the DNA force-versus-extension relation using a range of laser
      intensities, and show that these measurements match the expected extensible
      wormlike-chain (WLC) behavior. Finally, we also demonstrate a force-clamp, in
      which the tension in a tether is held fixed while the extension varies as a
      result of molecular events.

PMID- 23126751
TI  - Time-resolved multiple probe spectroscopy.
AB  - Time-resolved multiple probe spectroscopy combines optical, electronic, and data
      acquisition capabilities to enable measurement of picosecond to millisecond time
      resolved spectra within a single experiment, using a single activation pulse.
      This technology enables a wide range of dynamic processes to be studied on a
      single laser and sample system. The technique includes a 1 kHz pump, 10 kHz probe
      flash photolysis-like mode of acquisition (pump-probe-probe-probe, etc.),
      increasing the amount of information from each experiment. We demonstrate the
      capability of the instrument by measuring the photolysis of tungsten hexacarbonyl
      (W(CO)(6)) monitored by IR absorption spectroscopy, following picosecond
      vibrational cooling of product formation through to slower bimolecular diffusion
      reactions on the microsecond time scale.

PMID- 23126752
TI  - Non-degenerated photoluminescence excitation correlation spectroscopy using an
      optical sampling technique.
AB  - We have developed a highly time-resolved photoluminescence spectroscopy based on
      the excitation correlation method. Successive irradiation of a pair of ultrashort
      light pulses with different wavelength combinations taken from two sub-picosecond
      lasers has exposed both temporal and energetic correlation in photoluminescence
      intensity associated with a nonlinear response of a sample. An optical sampling
      technique has been introduced successfully in order to avoid consideration of the
      synchronization control of ultrashort light pulses. We have demonstrated the
      abilities of this technique by applying to the nonlinear photoluminescence
      dynamics of organic dye molecules in solution.

PMID- 23126753
TI  - A rapid reflectance-difference spectrometer for real-time semiconductor growth
      monitoring with sub-second time resolution.
AB  - We report on a rapid, 32-channel reflectance-difference (RD) spectrometer with
      sub-second spectra acquisition times and DeltaR/R sensitivity in the upper 10(-4)
      range. The spectrometer is based on a 50 kHz photo-elastic modulator for light
      polarization modulation and on a lock-in amplifier for signal harmonic analysis.
      Multichannel operation is allowed by multiplexing the 32 outputs of the
      spectrometer into the input of the lock-in amplifier. The spectrometer spans a
      wavelength range of 230 nm that can be tuned to cover E(1) and E(1) + Delta(1)
      transitions for a number of III-V semiconductors at epitaxial growth
      temperatures, including GaAs, InAs, AlAs, and their alloys. We present two
      examples of real-time measurements to demonstrate the performance of the RD
      spectrometer, namely, the evolution of the RD spectrum of GaAs (001) annealed at
      500  degrees C and the time-dependent RD spectrum during the first stages of the
      epitaxial growth of In(0.3)Ga(0.7)As on GaAs (001) substrates.

PMID- 23126754
TI  - Developing small vacuum spark as an x-ray source for calibration of an x-ray
      focusing crystal spectrometer.
AB  - A new technique of x-ray focusing crystal spectrometers' calibration is the
      desired result. For this purpose the spectrometer is designed to register
      radiated copper Kalpha and Kbeta lines by using a flat alpha-quartz crystal. This
      experiment uses pre-breakdown x-ray emissions in low vacuum of about 2.5-3 mbar.
      At this pressure the pinch will not form so the plasma will not radiate. The
      anode material is copper and the capacity of the capacitor bank is 22.6 nF. This
      experiment designed and mounted a repetitive triggering system to save the
      operator time making hundreds of shots. This emission amount is good for
      calibration and geometrical adjustment of an optical crystal x-ray focusing
      spectrometer.

PMID- 23126755
TI  - Kr II laser-induced fluorescence for measuring plasma acceleration.
AB  - We present the application of laser-induced fluorescence of singly ionized
      krypton as a diagnostic technique for quantifying the electrostatic acceleration
      within the discharge of a laboratory cross-field plasma accelerator also known as
      a Hall effect thruster, which has heritage as spacecraft propulsion. The 728.98
      nm Kr II transition from the metastable 5d(4)D(7/2) to the 5p(4)P(5/2)(?) state
      was used for the measurement of laser-induced fluorescence within the plasma
      discharge. From these measurements, it is possible to measure velocity as krypton
      ions are accelerated from near rest to approximately 21 km/s (190 eV). Ion
      temperature and the ion velocity distributions may also be extracted from the
      fluorescence data since available hyperfine splitting data allow for the Kr II
      5d(4)D(7/2)-5p(4)P(5/2)(?) transition lineshape to be modeled. From the analysis,
      the fluorescence lineshape appears to be a reasonable estimate for the relatively
      broad ion velocity distributions. However, due to an apparent overlap of the ion
      creation and acceleration regions within the discharge, the distributed velocity
      distributions increase ion temperature determination uncertainty significantly.
      Using the most probable ion velocity as a representative, or characteristic,
      measure of the ion acceleration, overall propellant energy deposition, and
      effective electric fields may be calculated. With this diagnostic technique, it
      is possible to nonintrusively characterize the ion acceleration both within the
      discharge and in the plume.

PMID- 23126756
TI  - X-ray luminescence based spectrometer for investigation of scintillation
      properties.
AB  - A new x-ray luminescence based spectrometer was developed and installed to
      examine the scintillation properties of materials while revealing the origins of
      luminescence and investigating trapping defects. Measurements were performed on a
      number of undoped and Ce doped yttrium aluminum garnet crystals and various
      luminescence centers were characterized. The measured x-ray luminescence spectra
      provide information about the spectral range and the scintillation efficiency and
      linearity. The efficiency of charge-carriers production due to x ray, their
      energy transfer to the luminescence centers, and the efficiency of luminescence
      are all reflected in the efficiency of x-ray luminescence.

PMID- 23126757
TI  - Thermal imaging diagnostics of high-current electron beams.
AB  - The thermal imaging diagnostics of measuring pulsed electron beam energy density
      is presented. It provides control of the electron energy spectrum and a measure
      of the density distribution of the electron beam cross section, the spatial
      distribution of electrons with energies in the selected range, and the total
      energy of the electron beam. The diagnostics is based on the thermal imager
      registration of the imaging electron beam thermal print in a material with low
      bulk density and low thermal conductivity. Testing of the thermal imaging
      diagnostics has been conducted on a pulsed electron accelerator TEU-500. The
      energy of the electrons was 300-500 keV, the density of the electron current was
      0.1-0.4 kA/cm(2), the duration of the pulse (at half-height) was 60 ns, and the
      energy in the pulse was up to 100 J. To register the thermal print, a thermal
      imager Fluke-Ti10 was used. Testing showed that the sensitivity of a typical
      thermal imager provides the registration of a pulsed electron beam heat pattern
      within one pulse with energy density over 0.1 J/cm(2) (or with current density
      over 10 A/cm(2), pulse duration of 60 ns and electron energy of 400 keV) with the
      spatial resolution of 0.9-1 mm. In contrast to the method of using radiosensitive
      (dosimetric) materials, thermal imaging diagnostics does not require either
      expensive consumables, or plenty of processing time.

PMID- 23126758
TI  - Temperature peaking at beginning of breakdown in 2.45 GHz pulsed off-resonance
      electron cyclotron resonance ion source hydrogen plasma.
AB  - An experimental study of temperature and density evolution during breakdown in
      off-resonance ECR hydrogen plasma is presented. Under square 2.45 GHz microwave
      excitation pulses with a frequency of 50 Hz and relative high microwave power,
      unexpected transient temperature peaks that reach 18 eV during 20 MUs are
      reported at very beginning of plasma breakdown. Decays of such peaks reach final
      stable temperatures of 5 eV at flat top microwave excitation pulse. Evidence of
      interplay between incoming power and duty cycle giving different kind of plasma
      parameters evolutions engaged to microwave coupling times is observed. Under
      relative high power conditions where short microwave coupling times are recorded,
      high temperature peaks are measured. However, for lower incoming powers and
      longer coupling times, temperature evolves gradually to a higher final
      temperature without peaking. On the other hand, the early instant where
      temperature peaks are observed also suggest a possible connection with preglow
      processes during breakdown in ECRIS plasmas.

PMID- 23126759
TI  - Measurement of parameters in Indus-2 synchrotron radiation source.
AB  - The paper presents the measurement of optics parameters in Indus-2 synchrotron
      radiation source, which include betatron tune, beta function, dispersion
      function, natural chromaticity, corrected chromaticity, central RF frequency,
      momentum compaction factor, and linear betatron coupling. Two methods were used
      for beta function measurement; a conventional quadrupole scan method and a method
      using the fitting of the orbit response matrix. A robust Levenberg-Marquardt
      algorithm was used for nonlinear least square fitting of the orbit response
      matrix. In this paper, detailed methods for the parameter measurements are
      described. The measured results are discussed and compared with the theoretical
      values obtained using accelerator simulation code Accelerator Toolbox in MATLAB.

PMID- 23126760
TI  - Variation of anode grid surface morphology and its effect on operation of a
      triode virtual cathode oscillator.
AB  - After repeatedly operation of a triode virtual cathode oscillator, the surface
      morphology of anode grid is studied by a scanning electron microscope. It is
      found that there are many quasi-periodic sawteeth formed on the anode grid, which
      are about 300-500 MUm in height, ~200 MUm in width, and 150-200 MUm in period.
      The formation of this sawteeth implies that there is possible Rayleigh-Taylor
      like instability on the anode grid during the irradiation by high-current
      relativistic electron beam. These sawteeth enhance the electric field on anode
      grid, leading to more feasible of anode plasma generation, and more rapidly
      expansion of that plasma. As a result, the electron transmissivity of anode grid
      is decreased, the output microwave power of the virtual cathode oscillator is
      lowered and its operational performance is degraded.

PMID- 23126761
TI  - Control of current and voltage oscillations in a short dc discharge making use of
      external auxiliary electrode.
AB  - A dc discharge with a hot cathode is subject to current and voltage plasma
      oscillations, which have deleterious effects on its operation. The oscillations
      can be inhibited by installing an auxiliary electrode, placed outside of anode.
      By collecting a modest current through a small opening in anode, we show that the
      discharge becomes stable, in a certain pressure range. This method of avoiding
      current oscillations can be used, for example, for high current stabilizers.

PMID- 23126762
TI  - Ion energy analyzer for measurement of ion turbulent transport.
AB  - For local measurement of radial ion thermal transport, we developed a novel time
      resolved gridded ion energy analyzer. The turbulent thermal flux is obtained by
      correlating fluctuations of ion temperature, plasma density and plasma velocity.
      The simultaneous measurement of the ion current fluctuations from an ion energy
      analyzer I(IEA)(t) and the fluctuation of ion saturation current from a
      conventional Langmuir probe I(LP)(t) allow us to determine local fluctuations of
      ion temperature T(i)(t). To reduce the effect of plasma potential fluctuations in
      the energy analyzer measurements, we use special a compensative circuit loop.

PMID- 23126763
TI  - A novel technique for single-shot energy-resolved 2D x-ray imaging of plasmas
      relevant for the inertial confinement fusion.
AB  - A novel x-ray diagnostic of laser-fusion plasmas is described, allowing 2D
      monochromatic images of hot, dense plasmas to be obtained in any x-ray photon
      energy range, over a large domain, on a single-shot basis. The device (named
      energy-encoded pinhole camera) is based upon the use of an array of many pinholes
      coupled to a large area CCD camera operating in the single-photon mode. The
      available x-ray spectral domain is only limited by the quantum efficiency of
      scientific-grade x-ray CCD cameras, thus extending from a few keV up to a few
      tens of keV. Spectral 2D images of the emitting plasma can be obtained at any x
      ray photon energy provided that a sufficient number of photons had been collected
      at the desired energy. Results from recent inertial confinement fusion related
      experiments will be reported in order to detail the new diagnostic.

PMID- 23126764
TI  - Diagnostics of underwater electrical wire explosion through a time- and space
      resolved hard x-ray source.
AB  - A time- and space-resolved hard x-ray source was developed as a diagnostic tool
      for imaging underwater exploding wires. A ~4 ns width pulse of hard x-rays with
      energies of up to 100 keV was obtained from the discharge in a vacuum diode
      consisting of point-shaped tungsten electrodes. To improve contrast and image
      quality, an external pulsed magnetic field produced by Helmholtz coils was used.
      High resolution x-ray images of an underwater exploding wire were obtained using
      a sensitive x-ray CCD detector, and were compared to optical fast framing images.
      Future developments and application of this diagnostic technique are discussed.

PMID- 23126765
TI  - Laser schlieren deflectometry for temperature analysis of filamentary non-thermal
      atmospheric pressure plasma.
AB  - The heat convection generated by micro filaments of a self-organized non-thermal
      atmospheric pressure plasma jet in Ar is characterized by employing laser
      schlieren deflectometry (LSD). It is demonstrated as a proof of principle, that
      the spatial and temporal changes of the refractive index n in the optical beam
      path related to the neutral gas temperature of the plasma jet can be monitored
      and evaluated simultaneously. The refraction of a laser beam in a high gradient
      field of n(r) with cylindrical symmetry is given for a general real refraction
      index profile. However, the usually applied Abel approach represents an ill-posed
      problem and in particular for this plasma configuration. A simple analytical
      model is proposed in order to minimize the statistical error. Based on that, the
      temperature profile, specifically the absolute temperature in the filament core,
      the FWHM, and the frequencies of the collective filament dynamics are obtained
      for non-stationary conditions. For a gas temperature of 700 K inside the
      filament, the presented model predicts maximum deflection angles of the laser
      beam of 0.3 mrad which is in accordance to the experimental results obtained with
      LSD. Furthermore, the experimentally obtained FWHM of the temperature profile
      produced by the filament at the end of capillary is (1.5 +/- 0.2) mm, which is
      about 10 times wider than the visual radius of the filament. The obtained maximum
      temperature in the effluent is (450 +/- 30) K and is in consistence with results
      of other techniques. The study demonstrates that LSD represents a useful low-cost
      method for monitoring the spatiotemporal behaviour of microdischarges and allows
      to uncover their dynamic characteristics, e.g., the temperature profile even for
      challenging diagnostic conditions such as moving thin discharge filaments. The
      method is not restricted to the miniaturized and self-organized plasma studied
      here. Instead, it can be readily applied to other configurations that produce
      measurable gradients of refractive index by local gas heating and opens new
      diagnostics prospects particularly for microplasmas.

PMID- 23126766
TI  - Oblique electron-cyclotron-emission radial and phase detector of rotating
      magnetic islands applied to alignment and modulation of electron-cyclotron
      current-drive for neoclassical tearing mode stabilization.
AB  - A two channel oblique electron cyclotron emission (ECE) radiometer was installed
      on the DIII-D tokamak and interfaced to four gyrotrons. Oblique ECE was used to
      toroidally and radially localize rotating magnetic islands and so assist their
      electron cyclotron current drive (ECCD) stabilization. In particular, after
      manipulations operated by the interfacing analogue circuit, the oblique ECE
      signals directly modulated the current drive in synch with the island rotation
      and in phase with the island O-point, for a more efficient stabilization. Apart
      from the different toroidal location, the diagnostic view is identical to the
      ECCD launch direction, which greatly simplified the real-time use of the signals.
      In fact, a simple toroidal extrapolation was sufficient to lock the modulation to
      the O-point phase. This was accomplished by a specially designed phase shifter of
      nearly flat response over the 1-7 kHz range. Moreover, correlation analysis of
      two channels slightly above and below the ECCD frequency allowed checking the
      radial alignment to the island, based on the fact that for satisfactory alignment
      the two signals are out of phase.

PMID- 23126767
TI  - Fourier transform infrared absorption spectroscopy characterization of gaseous
      atmospheric pressure plasmas with 2 mm spatial resolution.
AB  - This paper describes an optical setup built to record Fourier transform infrared
      (FTIR) absorption spectra in an atmospheric pressure plasma with a spatial
      resolution of 2 mm. The overall system consisted of three basic parts: (1)
      optical components located within the FTIR sample compartment, making it possible
      to define the size of the infrared beam (2 mm * 2 mm over a path length of 50 mm)
      imaged at the site of the plasma by (2) an optical interface positioned between
      the spectrometer and the plasma reactor. Once through the plasma region, (3) a
      retro-reflector module, located behind the plasma reactor, redirected the
      infrared beam coincident to the incident path up to a 45 degrees  beamsplitter to
      reflect the beam toward a narrow-band mercury-cadmium-telluride detector. The
      antireflective plasma-coating experiments performed with ammonia and silane
      demonstrated that it was possible to quantify 42 and 2 ppm of these species in
      argon, respectively. In the case of ammonia, this was approximately three times
      less than this gas concentration typically used in plasma coating experiments
      while the silane limit of quantification was 35 times lower. Moreover, 70% of the
      incoming infrared radiation was focused within a 2 mm width at the site of the
      plasma, in reasonable agreement with the expected spatial resolution. The
      possibility of reaching this spatial resolution thus enabled us to measure the
      gaseous precursor consumption as a function of their residence time in the
      plasma.

PMID- 23126768
TI  - Compact scanning tunneling microscope for spin polarization measurements.
AB  - We present a design for a scanning tunneling microscope that operates in
      ultrahigh vacuum down to liquid helium temperatures in magnetic fields up to 8 T.
      The main design philosophy is to keep everything compact in order to minimize the
      consumption of cryogens for initial cool-down and for extended operation. In
      order to achieve this, new ideas were implemented in the design of the microscope
      body, dewars, vacuum chamber, manipulators, support frame, and vibration
      isolation. After a brief description of these designs, the results of initial
      tests are presented.

PMID- 23126769
TI  - Interpreting atomic force microscopy measurements of hydrodynamic and surface
      forces with nonlinear parametric estimation.
AB  - A nonlinear parameter estimation method has been developed to extract the
      separation-dependent surface force and cantilever spring constant from atomic
      force microscope data taken at different speeds for the interaction between a
      silica colloidal probe and plate in aqueous solution. The distinguishing feature
      of this approach is that it exploits information from the velocity dependence of
      the force-displacement data due to hydrodynamic interaction to provide an
      unbiased estimate of the functional form of the separation-dependent surface
      force. An assumed function for the surface force with unknown parameters is not
      required. In addition, the analysis also yields a consistent estimate of the in
      situ cantilever spring constant. In combination with data from static force
      measurements, this approach can further be used to quantify the extent of
      hydrodynamic slip.

PMID- 23126770
TI  - Tip preparation for near-field ablation at mid-infrared wavelengths.
AB  - A fabrication method for high-throughput, fiber-based tips for near-field
      scanning microscopy (NSOM) in the mid-infrared (lambda ~ 3 MUm) has been
      developed. Several fiber materials have been investigated and recipes for wet
      chemical etching have been varied to produce tips that are physically robust and
      are capable of low-loss transmission of high-power pulses of mid-infrared light.
      Ultimately, wet-chemical etching techniques are used on glass fibers to produce
      tips capable of focusing mid-infrared light to ablate material from sub-micron
      sized regions of organic films. The power throughput of the tips is significantly
      increased by using a novel material, previously unreported for NSOM applications:
      germanate fibers. The tips produced are mechanically strong and capable of
      transmitting high light fluence without sustaining physical damage. Here, the
      development of these tips and their performance are described.

PMID- 23126771
TI  - Video-based and interference-free axial force detection and analysis for optical
      tweezers.
AB  - For measuring the minute forces exerted on single molecules during controlled
      translocation through nanopores with sub-piconewton precision, we have developed
      a video-based axial force detection and analysis system for optical tweezers.
      Since our detection system is equipped with a standard and versatile CCD video
      camera with a limited bandwidth offering operation at moderate light illumination
      with minimal sample heating, we integrated Allan variance analysis for trap
      stiffness calibration. Upon manipulating a microbead in the vicinity of a weakly
      reflecting surface with simultaneous axial force detection, interference effects
      have to be considered and minimized. We measured and analyzed the backscattering
      light properties of polystyrene and silica microbeads with different diameters
      and propose distinct and optimized experimental configurations (microbead
      material and diameter) for minimal light backscattering and virtually
      interference-free microbead position detection. As a proof of principle, we
      investigated the nanopore threading forces of a single dsDNA strand attached to a
      microbead with an overall force resolution of +/-0.5 pN at a sample rate of 123
      Hz.

PMID- 23126772
TI  - Spring constant calibration of atomic force microscope cantilevers of arbitrary
      shape.
AB  - The spring constant of an atomic force microscope cantilever is often needed for
      quantitative measurements. The calibration method of Sader et al. [Rev. Sci.
      Instrum. 70, 3967 (1999)] for a rectangular cantilever requires measurement of
      the resonant frequency and quality factor in fluid (typically air), and knowledge
      of its plan view dimensions. This intrinsically uses the hydrodynamic function
      for a cantilever of rectangular plan view geometry. Here, we present hydrodynamic
      functions for a series of irregular and non-rectangular atomic force microscope
      cantilevers that are commonly used in practice. Cantilever geometries of arrow
      shape, small aspect ratio rectangular, quasi-rectangular, irregular rectangular,
      non-ideal trapezoidal cross sections, and V-shape are all studied. This enables
      the spring constants of all these cantilevers to be accurately and routinely
      determined through measurement of their resonant frequency and quality factor in
      fluid (such as air). An approximate formulation of the hydrodynamic function for
      microcantilevers of arbitrary geometry is also proposed. Implementation of the
      method and its performance in the presence of uncertainties and non-idealities is
      discussed, together with conversion factors for the static and dynamic spring
      constants of these cantilevers. These results are expected to be of particular
      value to the design and application of micro- and nanomechanical systems in
      general.

PMID- 23126773
TI  - Brandaris 128 ultra-high-speed imaging facility: 10 years of operation, updates,
      and enhanced features.
AB  - The Brandaris 128 ultra-high-speed imaging facility has been updated over the
      last 10 years through modifications made to the camera's hardware and software.
      At its introduction the camera was able to record 6 sequences of 128 images (500
      * 292 pixels) at a maximum frame rate of 25 Mfps. The segmented mode of the
      camera was revised to allow for subdivision of the 128 image sensors into
      arbitrary segments (1-128) with an inter-segment time of 17 MUs. Furthermore, a
      region of interest can be selected to increase the number of recordings within a
      single run of the camera from 6 up to 125. By extending the imaging system with a
      laser-induced fluorescence setup, time-resolved ultra-high-speed fluorescence
      imaging of microscopic objects has been enabled. Minor updates to the system are
      also reported here.

PMID- 23126774
TI  - Development of thin-film tunable band-pass filters based hyper-spectral imaging
      system applied for both surface enhanced Raman scattering and plasmon resonance
      Rayleigh scattering.
AB  - We describe the development of a hyper-spectral imaging (HSI) system composed of
      thin-film tunable band-pass filters (TF-TBPFs) and its application to
      inhomogeneous sample surfaces. Compared with existing HSI systems, the system has
      a simpler optical arrangement and has an optical transmittance of up to 80% owing
      to polarization independence. The HSI system exhibits a constant spectral
      resolution over a spectral window of 80 nm (530 to 610 nm) and tunable spectral
      resolution from 1.5 to 3.0 nm, and requires only 5.4 s per measurement. Plasmon
      resonance and surface enhanced Raman scattering (SERS) from inhomogeneous
      surfaces dispersed with Ag nanoparticles (NP) have been measured with the HSI
      system. The measurement of multiple Ag NPs is consistent with conventional
      isolated NP measurements as explained by the electromagnetic mechanism of SERS,
      demonstrating the validity of the HSI system.

PMID- 23126775
TI  - Constant current etching of gold tips suitable for tip-enhanced Raman
      spectroscopy.
AB  - We introduce a setup and method to produce gold tips that are suitable for tip
      enhanced Raman spectroscopy by using a single step constant current
      electrochemical etch. The etching process is fully automated with only three
      preset parameters: the etching current, the reference voltage and the immersed
      length of gold wires. By optimizing these parameters, reproducible high quality
      tips with smooth surface and a radius curvature of about 20 nm can be formed.
      Tips prepared with this method were examined by tip-enhanced Raman spectroscopy
      experiments on the samples of single-wall carbon nanotube, p-aminothiophenol, and
      graphene. In the Raman mapping of single-wall carbon nanotubes, the spatial
      resolution is about 15 nm.

PMID- 23126776
TI  - Simplified laser-driven flyer plates for shock compression science.
AB  - We describe a simplified system of laser-driven flyer plates for shock
      compression science and shock spectroscopy. We used commercially available one
      box Nd:YAG lasers and beam homogenization solutions to create two launch systems,
      one based on a smaller (400 mJ) YAG laser and an inexpensive diffusive optic, and
      one based on a larger (2500 mJ) laser and a diffractive beam homogenizer. The
      flyer launch, flight, and impact processes were characterized by an 8 GHz
      fiberoptic photon Doppler velocimeter. We investigated effects of different
      substrates, adhesives, absorbers, ablative layers, and punching out disks from
      continuous foils versus fabricating individual foil disks, and found that a
      simple metal foil epoxied to a glass window was satisfactory in almost all cases.
      Our simplified system launched flyer plates with velocities up to 4.5 km s(-1)
      and kinetic energies up to 250 mJ that can drive sustained steady shocks for up
      to 25 ns. The factor that limits these velocities and energies is the laser
      fluence that can be transmitted through the glass substrate to the flyer surface
      without optical damage. Methods to increase this transmission are discussed.
      Reproducible flyer launches were demonstrated with velocity variations of 0.06%
      and impact time variations of 1 ns. The usefulness of this flyer plate system is
      demonstrated by Hugoniot equation of state measurements of a polymer film,
      emission spectroscopy of a dye embedded in the polymer, and impact initiation and
      emission spectroscopy of a reactive material consisting of nanoscopic fuel and
      oxidizer particles.

PMID- 23126777
TI  - Four-probe electrical measurements with a liquid pressure medium in a diamond
      anvil cell.
AB  - We describe a technique for making electrical transport measurements in a diamond
      anvil cell using an alcohol pressure medium, permitting acute sensitivity while
      preserving sample fidelity. The sample is suspended in the liquid medium by four
      gold leads that are electrically isolated by a composite gasket made of stainless
      steel and an alumina-loaded epoxy. We demonstrate the technique with four-probe
      resistivity measurements of chromium single crystals at temperatures down to 4 K
      and pressures above 10 GPa. Our assembly is optimized for making high precision
      measurements of the magnetic phase diagram and quantum critical regime of
      chromium, which require repeated temperature sweeps and fine pressure steps while
      maintaining high sample quality. The high sample quality enabled by the quasi
      hydrostatic pressure medium is evidenced by the residual resistivity below 0.1
      MUOmega cm and the relative resistivity ratio rho(120 K)/rho(5 K) = 15.9 at 11.4
      GPa. By studying the quality of Cr's antiferromagnetic transition over a range of
      pressures, we show that the pressure inhomogeneity experienced by the sample is
      always below 5%. Finally, we solve for the Debye temperature of Cr up to 11.4 GPa
      using the Bloch-Gruneisen formula and find it to be independent of pressure.

PMID- 23126778
TI  - A scanning tunneling microscope with a scanning range from hundreds of
      micrometers down to nanometer resolution.
AB  - A beetle type stage and a flexure scanning stage are combined to form a two
      stages scanning tunneling microscope (STM). It operates at room temperature in
      ultrahigh vacuum and is capable of scanning areas up to 300 MUm * 450 MUm down to
      resolution on the nanometer scale. This multi-scale STM has been designed and
      constructed in order to investigate prestructured metallic or semiconducting
      micro- and nano-structures in real space from atomic-sized structures up to the
      large-scale environment. The principle of the instrument is demonstrated on two
      different systems. Gallium nitride based micropillars demonstrate scan areas up
      to hundreds of micrometers; a Au(111) surface demonstrates nanometer resolution.

PMID- 23126779
TI  - A novel approach for normalizing the photoreflectance spectrum by using polymer
      dispersed liquid crystal.
AB  - This study developed a novel type of normalization procedure for modulation
      reflectance spectroscopy experiments to obtain the relative change in the
      reflectance spectrum, DeltaR/R. This technique uses a polymer-dispersed liquid
      crystal to ensure that the dc component of the signal from the detector remained
      constant by varying the intensity of the light striking the sample. This method
      is particularly useful for photoreflectance measurement, which may encounter
      background problems because of scattered pump light and/or photoluminescence. It
      does not require a change in the gain of the detector or the use of a variable
      neutral density filter mounted on a servo-motor.

PMID- 23126780
TI  - Momentum spectrometer for electron-electron coincidence studies on
      superconductors.
AB  - We present a new experimental setup to study electron-electron coincidences from
      superconducting surfaces. In our approach, electrons emitted from a surface are
      projected onto a time- and position-sensitive microchannel plate detector with
      delayline position readout. Electrons that are emitted within 2 pi solid angle
      with respect to the surface are detected in coincidence. The detector used is a
      hexagonal delayline detector with enhanced multiple hit capabilities. It is read
      out with a Flash analog-to-digital converter. The three-dimensional momentum
      vector is obtained for each electron. The intrinsic dead time of the detector has
      been greatly reduced by implementing a new algorithm for pulse analysis. The
      sample holder has been matched to fit the spectrometer while being capable of
      cooling down the sample to 4.5 K during the measurement and heating it up to 420
      K for the cleaning procedure.

PMID- 23126781
TI  - Direct structural characterisation of line gratings with grazing incidence small
      angle x-ray scattering.
AB  - Grazing incidence small-angle x-ray scattering (GISAXS) and x-ray reflectometry
      (XRR) have been used to investigate structural parameters, especially period
      length, line width, groove width, and line height, of grating test structures in
      the sub-micron range. The gratings are e-beam written structures on a quartz
      substrate with a fixed period length, but different line and groove widths,
      covered by a layer of ruthenium. A Ru layer thickness of 9.4 nm has been
      determined with XRR. GISAXS was performed in two orientations, with an incident
      beam alignment perpendicular and parallel to the grating lines. The scattering
      patterns in parallel orientation have been analysed without numerical simulation
      by Fourier transformation. The obtained results for line and groove width are in
      good agreement with nominal values. The analysis method has been validated by
      analysing simulated scattering data. A superposition of scattering intensities
      measured for different azimuthal rotation angles close to parallel alignment was
      used to determine the line height of a grating of 27.3 nm, which is also close to
      the nominal value. The Fourier analysis procedure opens up the possibility of
      traceable structure determination with GISAXS in the nanometre range.

PMID- 23126782
TI  - Noncontact technique for measuring the electrical resistivity and magnetic
      susceptibility of electrostatically levitated materials.
AB  - We describe the development of a new method for measuring the electrical
      resistivity and magnetic susceptibility of high temperature liquids and solids.
      The technique combines a tunnel diode oscillator with an electrostatic levitation
      furnace to perform noncontact measurements on spherical samples 2-3 mm in
      diameter. The tank circuit of the oscillator is inductively coupled to the
      sample, and measurements of the oscillator frequency as a function of sample
      temperature can be translated into changes in the sample's electrical resistivity
      and magnetic susceptibility. Particular emphasis is given on the need to improve
      the positional stability of the levitated samples, as well as the need to
      stabilize the temperature of the measurement coil. To demonstrate the validity of
      the technique, measurements have been performed on solid spheres of pure
      zirconium and low-carbon steel. In the case of zirconium, while absolute values
      of the resistivity were not determined, the temperature dependence of the
      resistivity was measured over the range of 640-1770 K and found to be in good
      agreement with literature data. In the case of low-carbon steel, the
      ferromagnetic-paramagnetic transition was clearly observable and, when combined
      with thermal data, appears to occur simultaneously with the solid-solid
      structural transition.

PMID- 23126783
TI  - Development of a method for measuring the density of liquid sulfur at high
      pressures using the falling-sphere technique.
AB  - We describe a new method for the in situ measurement of the density of a liquid
      at high pressure and high temperature using the falling-sphere technique.
      Combining synchrotron radiation X-ray radiography with a large-volume press, the
      newly developed falling-sphere method enables the determination of the density of
      a liquid at high pressure and high temperature based on Stokes' flow law. We
      applied this method to liquid sulfur and successfully obtained the density at
      pressures up to 9 GPa. Our method could be used for the determination of the
      densities of other liquid materials at higher static pressures than are currently
      possible.

PMID- 23126784
TI  - A digital receiver module with direct data acquisition for magnetic resonance
      imaging systems.
AB  - A digital receiver module for magnetic resonance imaging (MRI) with detailed
      hardware implementations is presented. The module is based on a direct sampling
      scheme using the latest mixed-signal circuit design techniques. A single field
      programmable gate array chip is employed to perform software-based digital down
      conversion for radio frequency signals. The modular architecture of the receiver
      allows multiple acquisition channels to be implemented on a highly integrated
      printed circuit board. To maintain the phase coherence of the receiver and the
      exciter in the context of direct sampling, an effective phase synchronization
      method was proposed to achieve a phase deviation as small as 0.09 degrees . The
      performance of the described receiver module was verified in the experiments for
      both low- and high-field (0.5 T and 1.5 T) MRI scanners and was compared to a
      modern commercial MRI receiver system.

PMID- 23126785
TI  - Defect characterisation based on heat diffusion using induction thermography
      testing.
AB  - Pulsed eddy current (PEC) thermography (a.k.a. induction thermography) has been
      successfully applied to detect defects (corrosion, cracks, impact, and
      delamination) in metal alloy and carbon fiber reinforced plastic. During these
      applications, the defect detection mechanism is mainly investigated based on the
      eddy current interaction with defect. In this paper, defect characterisation for
      wall thinning defect and inner defect in steel is investigated based on heat
      diffusion. The paper presents the PEC thermography testing, which integrates the
      reflection mode and transmission mode by means of configuring two cameras on both
      sides of sample. The defect characterisation methods under transmission mode and
      reflection mode are investigated and compared through 1D analytical analysis, 3D
      numerical studies, and experimental studies. The suitable detection mode for wall
      thinning and inner defects quantification is concluded.

PMID- 23126786
TI  - An earth-isolated optically coupled wideband high voltage probe powered by
      ambient light.
AB  - An earth-isolated optically-coupled wideband high voltage probe has been
      developed for pulsed power applications. The probe uses a capacitive voltage
      divider coupled to a fast light-emitting diode that converts high voltage into an
      amplitude-modulated optical signal, which is then conveyed to a receiver via an
      optical fiber. A solar cell array, powered by ambient laboratory lighting,
      charges a capacitor that, when triggered, acts as a short-duration power supply
      for an on-board amplifier in the probe. The entire system has a noise level
      <=0.03 kV, a DC-5 MHz bandwidth, and a measurement range from -6 to 2 kV; this
      range can be conveniently adjusted.

PMID- 23126787
TI  - A low-noise large dynamic-range readout suitable for laser spectroscopy with
      photodiodes.
AB  - An original low-noise large dynamic-range readout system for optical light
      spectroscopy with PIN diodes is presented. The front-end circuit is equipped with
      a smart device for automatic cancellation of the large dc offset brought about by
      the photodiode current. This device sinks away the exact amount of dc current
      from the preamplifier input, yielding auto zeroing of the output-voltage offset,
      while introducing the minimum electronic noise possible. As a result the
      measurement dynamic-range is maximized. Moreover, an auxiliary inspection point
      is provided which precisely tracks the dc component of the photodiode current.
      This output allows for precise beam alignment and may also be used for diagnostic
      purposes. The excellent gain stability and linearity make the circuit perfectly
      suited for optical-light pulse spectroscopy. Applications include particle sizing
      in the 100 nm range, two-dimensional characterization of semiconductor detectors,
      ultra-precise characterization of laser beam stability, confocal microscopy.

PMID- 23126788
TI  - Plasma-filled diode based on the coaxial gun.
AB  - The paper presents the results of studies of a coaxial gun for a plasma-filled
      electron diode. Effects of the discharge channel diameter and gun current on
      characteristics of the plasma and pulse generated in the diode were investigated.
      The electron beam with maximum energy of >=1 MeV at the current of ~100 kA was
      obtained in the experiments with a plasma-filled diode. The energy of ~5 kJ with
      the peak power of >=100 GW dissipated in the diode.

PMID- 23126789
TI  - Compact microwave cavity for high performance rubidium frequency standards.
AB  - The design, realization, and characterization of a compact magnetron-type
      microwave cavity operating with a TE(011)-like mode are presented. The resonator
      works at the rubidium hyperfine ground-state frequency (i.e., 6.835 GHz) by
      accommodating a glass cell of 25 mm diameter containing rubidium vapor. Its
      design analysis demonstrates the limitation of the loop-gap resonator lumped
      model when targeting such a large cell, thus numerical optimization was done to
      obtain the required performances. Microwave characterization of the realized
      prototype confirmed the expected working behavior. Double-resonance and Zeeman
      spectroscopy performed with this cavity indicated an excellent microwave magnetic
      field homogeneity: the performance validation of the cavity was done by achieving
      an excellent short-term clock stability as low as 2.4 * 10(-13) tau(-1/2). The
      achieved experimental results and the compact design make this resonator suitable
      for applications in portable atomic high-performance frequency standards for both
      terrestrial and space applications.

PMID- 23126790
TI  - Image reconstruction based on L1 regularization and projection methods for
      electrical impedance tomography.
AB  - Electrical impedance tomography (EIT) is a technique for reconstructing the
      conductivity distribution by injecting currents at the boundary of a subject and
      measuring the resulting changes in voltage. Image reconstruction in EIT is a
      nonlinear and ill-posed inverse problem. The Tikhonov method with L(2)
      regularization is always used to solve the EIT problem. However, the L(2) method
      always smoothes the sharp changes or discontinue areas of the reconstruction.
      Image reconstruction using the L(1) regularization allows addressing this
      difficulty. In this paper, a sum of absolute values is substituted for the sum of
      squares used in the L(2) regularization to form the L(1) regularization, the
      solution is obtained by the barrier method. However, the L(1) method often
      involves repeatedly solving large-dimensional matrix equations, which are
      computationally expensive. In this paper, the projection method is combined with
      the L(1) regularization method to reduce the computational cost. The L(1) problem
      is mainly solved in the coarse subspace. This paper also discusses the strategies
      of choosing parameters. Both simulation and experimental results of the L(1)
      regularization method were compared with the L(2) regularization method,
      indicating that the L(1) regularization method can improve the quality of image
      reconstruction and tolerate a relatively high level of noise in the measured
      voltages. Furthermore, the projected L(1) method can also effectively reduce the
      computational time without affecting the quality of reconstructed images.

PMID- 23126791
TI  - Optimal filter bandwidth for pulse oximetry.
AB  - Pulse oximeters contain one or more signal filtering stages between the
      photodiode and microcontroller. These filters are responsible for removing the
      noise while retaining the useful frequency components of the signal, thus
      improving the signal-to-noise ratio. The corner frequencies of these filters
      affect not only the noise level, but also the shape of the pulse signal. Narrow
      filter bandwidth effectively suppresses the noise; however, at the same time, it
      distorts the useful signal components by decreasing the harmonic content. In this
      paper, we investigated the influence of the filter bandwidth on the accuracy of
      pulse oximeters. We used a pulse oximeter tester device to produce stable,
      repetitive pulse waves with digitally adjustable R ratio and heart rate. We built
      a pulse oximeter and attached it to the tester device. The pulse oximeter
      digitized the current of its photodiode directly, without any analog signal
      conditioning. We varied the corner frequency of the low-pass filter in the pulse
      oximeter in the range of 0.66-15 Hz by software. For the tester device, the R
      ratio was set to R = 1.00, and the R ratio deviation measured by the pulse
      oximeter was monitored as a function of the corner frequency of the low-pass
      filter. The results revealed that lowering the corner frequency of the low-pass
      filter did not decrease the accuracy of the oxygen level measurements. The lowest
      possible value of the corner frequency of the low-pass filter is the fundamental
      frequency of the pulse signal. We concluded that the harmonics of the pulse
      signal do not contribute to the accuracy of pulse oximetry. The results achieved
      by the pulse oximeter tester were verified by human experiments, performed on
      five healthy subjects. The results of the human measurements confirmed that
      filtering out the harmonics of the pulse signal does not degrade the accuracy of
      pulse oximetry.

PMID- 23126792
TI  - Probing anisotropic heat transport using time-domain thermoreflectance with
      offset laser spots.
AB  - An analytic solution is derived for the time-domain thermoreflectance signal that
      occurs using non-concentric pump and probe beams on multilayer anisotropic
      materials. When in-plane heat transport is negligible, the experimental signal is
      the same as for the concentric case. However, for samples where in-plane heat
      diffusion distances are comparable to the spot size, the signal is sensitive to
      in-plane heat transport. This sensitivity to in-plane transport can be exploited
      to measure the in-plane thermal conductivity. Examples with experimental data are
      given for thin-film Al and the in-plane thermal conductivity of pyrolytic
      graphite.

PMID- 23126793
TI  - Decoupled cantilever arms for highly versatile and sensitive temperature and heat
      flux measurements.
AB  - Microfabricated cantilever beams have been used in microelectromechanical systems
      for a variety of sensor and actuator applications. Bimorph cantilevers accurately
      measure temperature change and heat flux with resolutions several orders of
      magnitude higher than those of conventional sensors such as thermocouples,
      semiconductor diodes, as well as resistance and infrared thermometers. The use of
      traditional cantilevers, however, entails a series of important measurement
      limitations, because their interactions with the sample and surroundings often
      create parasitic deflection forces and the typical metal layer degrades the
      thermal sensitivity of the cantilever. The paper introduces a design to address
      these issues by decoupling the sample and detector section of the cantilever,
      along with a thermomechanical model, the fabrication, system integration, and
      characterization. The custom-designed bi-arm cantilever is over one order of
      magnitude more sensitive than current commercial cantilevers due to the
      significantly reduced thermal conductance of the cantilever sample arm. The rigid
      and immobile sample section offers measurement versatility ranging from
      photothermal absorption, near-field thermal radiation down to contact,
      conduction, and material thermal characterization measurements in nearly
      identical configurations.

PMID- 23126794
TI  - Simultaneous measurement of external refractive index and temperature based on
      long-period-grating-inscribed Sagnac interferometer and fiber Bragg grating.
AB  - A compact Sagnac interferometer with a long-period grating (LPG) inscribed in a
      polarization-maintaining fiber (PMF-LPG) and a fiber Bragg grating (FBG) is
      proposed. The PMF-LPG is intrinsically sensitive to the external refractive index
      (ERI) and temperature, whereas the FBG is only sensitive to temperature.
      Simultaneous measurement of the ERI and temperature can be achieved by detecting
      wavelength shifts in the interference patterns of the Sagnac interferometer and
      the FBG. Because a Sagnac interference structure is used, a high ERI sensitivity
      of -21.07 nm/refractive index unit in measurement range 1.33-1.43 is obtained,
      which is about three times higher than for the normal LPG ERI sensor.

PMID- 23126795
TI  - Integrated automated nanomanipulation and real-time cellular surface imaging for
      mechanical properties characterization.
AB  - Surface microscopy of individual biological cells is essential for determining
      the patterns of cell migration to study the tumor formation or metastasis. This
      paper presents a correlated and effective theoretical and experimental technique
      to automatically address the biophysical and mechanical properties and acquire
      live images of biological cells which are of interest in studying cancer. In the
      theoretical part, a distributed-parameters model as the comprehensive
      representation of the microcantilever is presented along with a model of the
      contact force as a function of the indentation depth and mechanical properties of
      the biological sample. Analysis of the transfer function of the whole system in
      the frequency domain is carried out to characterize the stiffness and damping
      coefficients of the sample. In the experimental section, unlike the conventional
      atomic force microscope techniques basically using the laser for determining the
      deflection of microcantilever's tip, a piezoresistive microcantilever serving as
      a force sensor is implemented to produce the appropriate voltage and measure the
      deflection of the microcantilever. A micromanipulator robotic system is
      integrated with the MATLAB((r)) and programmed in such a way to automatically
      control the microcantilever mounted on the tip of the micromanipulator to achieve
      the topography of biological samples including the human corneal cells. For this
      purpose, the human primary corneal fibroblasts are extracted and adhered on a
      sterilized culture dish and prepared to attain their topographical image. The
      proposed methodology herein allows an approach to obtain 2D quality images of
      cells being comparatively cost effective and extendable to obtain 3D images of
      individual cells. The characterized mechanical properties of the human corneal
      cell are furthermore established by comparing and validating the phase shift of
      the theoretical and experimental results of the frequency response.

PMID- 23126796
TI  - A photonic wall pressure sensor for fluid mechanics applications.
AB  - In this paper, we demonstrate a micro-optical wall pressure sensor concept based
      on the optical modes of dielectric resonators. The sensing element is a spherical
      micro-resonator with a diameter of a few hundred micrometers. A latex membrane
      that is flush mounted on the wall transmits the normal pressure to the sensing
      element. Changes in the wall pressure perturb the sphere's morphology, leading to
      a shift in the optical modes. The wall pressure is measured by monitoring the
      shifts in the optical modes. Prototype sensors with polydimethylsiloxane micro
      spheres are tested in a steady two-dimensional channel flow and in a plane wave
      acoustic tube. Results indicate sensor resolutions of ~20 mPa and bandwidth of up
      to 2 kHz.

PMID- 23126797
TI  - On-chip stress relaxation testing method for freestanding thin film materials.
AB  - A stress relaxation method for freestanding thin films is developed based on an
      on-chip internal stress actuated microtensile testing set-up. The on-chip test
      structures are produced using microfabrication techniques involving cleaning,
      deposition, lithography, and release. After release from the substrate, the test
      specimens are subjected to uniaxial tension. The applied load decays with the
      deformation taking place during relaxation. This technique is adapted to strain
      rates lower than 10(-6)/s and permits the determination of the strain rate
      sensitivity of very thin films. The main advantage of the technique is that the
      relaxation tests are simultaneously performed on thousands of specimens, pre
      deformed up to different strain levels, for very long periods of time without
      monopolizing any external mechanical loading equipment. Proof of concept results
      are provided for 205-nm-thick sputtered AlSi(0.01) films and for 350-nm-thick
      evaporated Pd films showing unexpectedly high relaxation at room temperature.

PMID- 23126798
TI  - A platform to parallelize planar surfaces and control their spatial separation
      with nanometer resolution.
AB  - Parallelizing planar surfaces and manipulating them into close proximity with
      spatial separation of nanoscale dimensions is critical for probing phenomena such
      as near-field radiative heat transport and Casimir forces. Here, we report on a
      novel platform, with an integrated reflected light microscope, that is capable of
      parallelizing two planar surfaces such that the angular deviation is <6 MUrad,
      while simultaneously allowing control of the gap from 15 MUm down to contact with
      ~0.15 nm resolution. The capabilities of this platform were verified by using two
      custom-fabricated micro-devices with planar surfaces, 60 * 60 MUm(2) each, whose
      flatness and surface roughness were experimentally quantified. We first
      parallelized the two micro-devices by using the developed platform in conjunction
      with a simple optical approach that relies on the shallow depth of field (~2 MUm)
      of a long working distance microscope objective. Subsequently, we experimentally
      tested the parallelism achieved via the optical alignment procedure by taking
      advantage of electrodes integrated into the micro-devices. Our measurements
      unambiguously show that the simple depth-of-field based optical approach enables
      parallelization such that the angular deviation between the two surfaces is
      within ~500 MUrad. This ensures that the separation between any two corresponding
      points on the parallel surfaces deviate by ~30 nm or less from the expected
      value. Further, we show that improved parallelization can be achieved using the
      integrated micro-electrodes which enable surface roughness limited
      parallelization with deviations of ~5 nm from parallelism.

PMID- 23126799
TI  - A measurement system for an automatic survey of low frequency magnetic and
      electric fields.
AB  - In this paper we propose and verify by experiment a measurement system capable to
      survey both magnetic (H) and electric (E) fields at the same point, considering
      that the existing low frequency (50 Hz-10 kHz) instruments permit the survey at
      two different points, one for H and the other for E. This measurement system has
      a sensor with a special configuration, with a sensitivity to electric field of
      1.3 mV/(V/m), and a sensitivity to magnetic induction of 143 mV/MUT. The
      instrument is suitable for long term survey of low frequency H and E fields by
      making spot measurements of the fields, both time domain and frequency domain
      representations of H and E. The correlation between the theoretical analysis of
      the instrument and the experimental results was very good. The proposed
      measurement system was used for an automatic survey of background magnetic and
      electric fields generated by power line in a room from an apartment building.
      These results are presented in this paper, highlighting the performances of the
      instrument.

PMID- 23126800
TI  - Comparative evaluation of ultrasound scanner accuracy in distance measurement.
AB  - The aim of the present study is to develop and compare two different automatic
      methods for accuracy evaluation in ultrasound phantom measurements on B-mode
      images: both of them give as a result the relative error e between measured
      distances, performed by 14 brand new ultrasound medical scanners, and nominal
      distances, among nylon wires embedded in a reference test object. The first
      method is based on a least squares estimation, while the second one applies the
      mean value of the same distance evaluated at different locations in ultrasound
      image (same distance method). Results for both of them are proposed and
      explained.

PMID- 23126801
TI  - Isothermal titration calorimetry as a tool to determine the thermodynamics of
      demicellization processes.
AB  - Demicellization  of a 90 mM sodium dodecyl sulfate (SDS) solution in water at 10,
      22, and 30  degrees C was studied by isothermal titration calorimetry (ITC).
      DeltaH of the demicellization process was strongly temperature dependent, having
      an exothermic progression (-20.4 +/- 0.9 kJ/mol, max) at 10  degrees C and an
      endothermic one (3.7 +/- 1.2 kJ/mol, max) at 30  degrees C. DeltaH for micelle
      dilution followed a slightly endothermic progression (0.9 +/- 0.5 kJ/mol at 30 
      degrees C, 0.7 +/- 1.3 kJ/mol at 22  degrees C, and 0.0 +/- 0.5 kJ/mol at 10 
      degrees C) at all studied temperatures. No differences in DeltaH for micelle
      dilution and demicellization was observed at 22  degrees C. The temperature
      dependence of DeltaH measured by ITC could be related to hydrophobic
      interactions. Therefore, ITC was shown to be a useful tool to describe the
      thermodynamics of demicellization processes and in addition to determine
      alterations in DeltaH caused by changes in hydrophobic and steric/electrostatic
      interactions.

PMID- 23126802
TI  - New device to measure dynamic intrusion/extrusion cycles of lyophobic
      heterogeneous systems.
AB  - Lyophobic heterogeneous systems (LHS) are made of mesoporous materials immersed
      in a non-wetting liquid. One application of LHS is the nonlinear damping of high
      frequency vibrations. The behaviour of LHS is characterized by P - DeltaV cycles,
      where P is the pressure applied to the system, and DeltaV its volume change due
      to the intrusion of the liquid into the pores of the material, or its extrusion
      out of the pores. Very few dynamic studies of LHS have been performed until now.
      We describe here a new apparatus that allows us to carry out dynamic
      intrusion/extrusion cycles with various liquid/porous material systems,
      controlling the temperature from ambient to 120  degrees C and the frequency from
      0.01 to 20 Hz. We show that for two LHS: water/MTS and Galinstan/CPG, the energy
      dissipated during one cycle depends very weakly on the cycle frequency, in strong
      contrast to conventional dampers.

PMID- 23126803
TI  - Vacuum-integrated electrospray deposition for highly reliable polymer thin film.
AB  - Vacuum electrospray deposition (ESD) equipment was designed to prepare polymer
      thin films. The polymer solution can be injected directly into vacuum system
      through multi-stage pumping line, so that the solvent residues and ambient
      contaminants are highly reduced. To test the performance of ESD system, we
      fabricated organic photovoltaic cells (OPVCs) by injecting polymer solution
      directly onto the substrate inside a high vacuum chamber. The OPVC fabricated has
      the structure of Al/P3HT:PCBM/PEDOT:PSS/ITO and was optimized by varying the
      speed of solution injection and concentration of the solution. The power
      conversion efficiency (PCE) of the optimized OPVC is 3.14% under AM 1.5G
      irradiation without any buffer layer at the cathode side. To test the advantages
      of the vacuum ESD, we exposed the device to atmosphere between the deposition
      steps of the active layer and cathode. This showed that the PCE of the vacuum
      processed device is 24% higher than that of the air exposed device and confirms
      the advantages of the vacuum prepared polymer film for high performance devices.

PMID- 23126804
TI  - A test stand for the evaluation of high efficiency mist eliminators.
AB  - High efficiency mist eliminators (HEME) are airstream filtering elements
      primarily used to remove liquid and solid aerosols. HEME elements are designed to
      reduce aerosol load on downstream high efficiency particulate air filters and to
      have a liquid particle removal efficiency of 99.5% for aerosols as small as 1 MUm
      in size. The test stand described herein is designed to evaluate the loading
      capacity and filtering efficiency of a single HEME element. The loading capacity
      was determined with or without use of a water spray cleaning system to wash the
      interior surface of the element. The HEME element is challenged with a liquid
      waste surrogate using Laskin nozzles and large dispersion nozzles. The waste
      surrogate used was a highly caustic solution with both suspended and dissolved
      solids representative of actual exposures at mixed, hazardous, and radiological,
      waste treatment facilities. The filtering efficiency performance was determined
      by challenging the element with a dried waste surrogate aerosol and di-octyl
      phthalate intermittently during the loading process. Capabilities of the test
      stand and representative results obtained during testing are presented.

PMID- 23126805
TI  - On the performance enhancement of adaptive signal averaging: a means for
      improving the sensitivity and rate of data acquisition in magnetic resonance and
      other analytical measurements.
AB  - A few years back, our lab developed a signal averaging technique that greatly
      reduces the number of scans required to achieve a comparable signal-to-noise
      ratio to that of conventional signal averaging for continuous wave magnetic
      resonance measurements. We utilize an adaptive filter in a signal averaging
      scheme without any prior knowledge of the signal under observation. We termed
      this technique adaptive signal averaging (ASA). The technique was successful in
      reducing the noise variance by a factor of at least 10 in a single trace and is
      shown to converge in time by the same factor. ASA can also be useful in many
      other applications where signal averaging is utilized, such as medical imaging,
      electrocardiography, or electroencephalography. The purpose of this paper is to
      describe the advancements made to the technique, present a derivation of its
      performance enhancement, and illustrate the power of the technique through a set
      of simulations.

PMID- 23126806
TI  - In situ cleaning of instruments for the sensitive detection of organics on Mars.
AB  - A method is presented for in situ cleaning of spacecraft instruments that analyze
      planetary soil and rock. We have found that vibrating hardware, used to
      facilitate powder transport, was also effective at removing contamination.
      Surfaces can be cleaned below monolayer levels using vibrating surfaces in the
      presence of mineral powder. Both organic and particulate contamination is
      efficiently removed. Fine grained regolith from the planetary surface or an
      organic free reference material may serve as the powder used for cleaning. We
      present both analytical and experimental results for the contamination transfer
      fraction and the conditions required to clean the hardware prior to sensitive
      chemical analysis.

PMID- 23126807
TI  - Towards a beyond 1 GHz solid-state nuclear magnetic resonance: external lock
      operation in an external current mode for a 500 MHz nuclear magnetic resonance.
AB  - Achieving a higher magnetic field is important for solid-state nuclear magnetic
      resonance (NMR). But a conventional low temperature superconducting (LTS) magnet
      cannot exceed 1 GHz (23.5 T) due to the critical magnetic field. Thus, we started
      a project to replace the Nb(3)Sn innermost coil of an existing 920 MHz NMR (21.6
      T) with a Bi-2223 high temperature superconducting (HTS) innermost coil.
      Unfortunately, the HTS magnet cannot be operated in persistent current mode; an
      external dc power supply is required to operate the NMR magnet, causing magnetic
      field fluctuations. These fluctuations can be stabilized by a field-frequency
      lock system based on an external NMR detection coil. We demonstrate here such a
      field-frequency lock system in a 500 MHz LTS NMR magnet operated in an external
      current mode. The system uses a (7)Li sample in a microcoil as external NMR
      detection system. The required field compensation is calculated from the
      frequency of the FID as measured with a frequency counter. The system detects the
      FID signal, determining the FID frequency, and calculates the required
      compensation coil current to stabilize the sample magnetic field. The magnetic
      field was stabilized at 0.05 ppm/3 h for magnetic field fluctuations of around 10
      ppm. This method is especially effective for a magnet with large magnetic field
      fluctuations. The magnetic field of the compensation coil is relatively
      inhomogeneous in these cases and the inhomogeneity of the compensation coil can
      be taken into account.

PMID- 23126808
TI  - A design for a compact time-of-flight mass spectrometer.
AB  - The design of a prototype, compact time-of-flight (TOF) mass spectrometer is
      described. The system primarily consists of an ion acceleration/focusing/steering
      assembly (AFSA), an 8 cm field-free region, a 4 cm dual-stage reflectron, and a
      miniature microchannel plate detector. Consequently, the resulting flight length
      of the system is 12 cm. The system has been designed with the capability to
      sample directly from atmosphere at ambient pressures. This is accomplished
      through the use of an electrodynamic ion funnel, housed in an intermediate-vacuum
      chamber that is coupled to the inlet of the TOF chamber. TOF spectra were
      obtained using noble gases (Ar, Kr, and Xe) as test chemicals. These measured
      flight times were used to probe the performance of the instrument. A temporal
      resolution (t(flight)/Deltat) of approximately 125, acquired using (129)Xe(+),
      has been measured for the system.

PMID- 23126809
TI  - A portable molecular beam epitaxy system for in situ x-ray investigations at
      synchrotron beamlines.
AB  - A portable synchrotron molecular beam epitaxy (MBE) system is designed and
      applied for in situ investigations. The growth chamber is equipped with all the
      standard MBE components such as effusion cells with shutters, main shutter,
      cooling shroud, manipulator, reflection high energy electron diffraction setup,
      and pressure gauges. The characteristic feature of the system is the beryllium
      windows which are used for in situ x-ray measurements. An UHV sample transfer
      case allows in vacuo transfer of samples prepared elsewhere. We describe the
      system design and demonstrate its performance by investigating the annealing
      process of buried InGaAs self-organized quantum dots.

PMID- 23126810
TI  - Electrical ammeter based on spin-valve sensor.
AB  - The present work shows an electrical ammeter for laboratory purpose based on a
      magnetoresistive (MR) spin-valve (SV) sensor. The proposed ammeter measures a 10
      A maximum current and offers a maximum frequency response between 150 and 800 kHz
      depending on the electronics whole gain. These features are due to the use of a
      new generation MR-SV current sensor and a conditioning electronics that
      compensates in frequency and temperature the sensor response. With little
      adjustments in the electronics and changing the position of the sensor with
      respect to current carrying conductor, the designed instrument is able to measure
      higher current levels. The work shows the proposed ammeter with its different
      subsystems and describes the procedure used to test the instrument. Also a
      discussion of the obtained experimental results is included.

PMID- 23126811
TI  - Design, modeling, and performance evaluation of a novel dye cell for a high
      repetition rate dye laser.
AB  - In this paper, a new dye cell for transverse pumping was designed, modeled, and
      its performance in a narrow spectral width dispersive resonator, pumped by a high
      repetition rate copper vapor laser, was investigated. The scheme essentially
      involves the profiling of the cubical glass and stainless steel cylindrical
      surface such that convex-plano contour be present near the optical pumping
      region. The design is an amalgamation of straight and curved periphery to enhance
      the dye solution flow stabilities near the dye laser axis. A computational fluid
      dynamics analysis of the liquid flow through this dye cell has been carried out.
      The dye laser outputs such as optical average power, spectral width and
      wavelength stability, tuning range, pulse shape, through this new dye cell was
      evaluated. The dye laser average power about 30 mW was fairly steady over the
      observation period of more than an hour. The dye laser short-term (1 min)
      spectral width was within 0.824 +/- 0.075 GHz, while, in a long-term, more than
      an hour, drifted by about 180 MHz. The dye laser wavelength in short-term
      fluctuates within +/-0.0065 nm whereas in a long-term, more than an hour, drifted
      by about 0.0105 nm. The dye laser tuning range was 10 nm with a sub GHz spectral
      width operation. The pulse shape of the dye laser follows the pump laser pulse
      profile. Thus, the dye laser has demonstrated fairly long-term stability, without
      the use of either low expansion material or close loop control on the output.

PMID- 23126812
TI  - Chronocoulometry for quantitative control of mass removal in micro-structures and
      sensors.
AB  - In this work, tungsten wires have been etched in a KOH electrolyte solution.
      Based on the oxidation state of the electrolytic dissolution reaction's product
      and time integration of the Faradaic current produced during the reaction, this
      method is capable of providing a direct measurement of the change in mass of a
      structure from anodic dissolution. To assess the application of this process for
      controlled mass removal spanning sub-micrograms to milligrams, two experimental
      studies and accompanying uncertainty analyses have been undertaken. In the first
      of these, 5 tungsten wires of length 30 mm were used to remove mass values
      ranging from 50 to 350 MUg. Uncertainty estimates indicate relative combined
      standard uncertainties of less than 0.3% in the mass changes determined from the
      measurement of Faradaic current. Comparison of the mass change determined using
      the electrolytic method, and using a precision ultra-microbalance agreed within
      this uncertainty. The charge-based method was then applied to modify the dynamic
      characteristics of a quartz tuning fork oscillator. In these experiments,
      tungsten fiber attached to one tine of the oscillator was etched in 5 MUg
      increments up to 120 MUg of total removed mass. In general, frequency shifts of
      2.8 Hz . MUg(-1) were observed, indicating sub-microgram resolution for the
      characterization of probes based on frequency shift and charge-based mass
      measurement. Taken together, this study provides the basis for a precision method
      for determining changes in mass based on electrical measurements from an
      electrochemical system. The utility of this technique is demonstrated through
      controlled modification of the dynamic properties of a mechanical oscillator.

PMID- 23126813
TI  - A prototype mass spectrometer for in situ analysis of cave atmospheres.
AB  - Research in cave environments has many applications: studying local hydrogeologic
      activity, paleoclimate studies, analyzing white nose syndrome in bat populations,
      analogs for underground atmospheres in mining facilities, carbon sequestration
      efforts, and terrestrial analogs for planetary caves. The atmospheres of many
      caves contain tracers of current geological and biological activity, but up to
      this point, in situ studies have been limited to sensors that monitor individual
      components of the cave atmosphere. A prototype cave mass spectrometer system was
      assembled from commercial off-the-shelf parts to conduct surveys of atmospheric
      compositions inside four local Texas caves and to perform atmospheric analysis of
      two aquifer wellheads to a depth of 60 m. We found increased levels of CO(2) in
      all caves and, surprisingly, increased levels of O(2) in Bracken Bat Cave.
      Aquifer wellhead measurements showed indications of methane, other hydrocarbons,
      and other constituents not anticipated.

PMID- 23126814
TI  - Design and optimization of voice coil actuator for six degree of freedom active
      vibration isolation system using Halbach magnet array.
AB  - This paper describes the design, modeling, optimization, and validation of an
      active vibration isolation system using a voice coil motor. The active vibration
      isolating method was constructed with a passive isolator and an active isolator.
      A spring was used for passive isolating; an actuator was used for active
      isolating. The proposed active vibration isolation system (AVIS) can isolate
      disturbances for many kinds of instruments. Until now, developed AVIS were able
      to isolate a six degree-of-freedom disturbance effectively. This paper proposes
      the realization of such a six degree-of-freedom active vibration isolation system
      that can work as a bench top device for precision measuring machines such as
      atomic force microscope, scanning probe microscope, etc.

PMID- 23126815
TI  - Note: Quasi-real-time analysis of dynamic near field scattering data using a
      graphics processing unit.
AB  - We present an implementation of the analysis of dynamic near field scattering
      (NFS) data using a graphics processing unit. We introduce an optimized data
      management scheme thereby limiting the number of operations required. Overall, we
      reduce the processing time from hours to minutes, for typical experimental
      conditions. Previously the limiting step in such experiments, the processing time
      is now comparable to the data acquisition time. Our approach is applicable to
      various dynamic NFS methods, including shadowgraph, Schlieren and differential
      dynamic microscopy.

PMID- 23126816
TI  - Note: Development of a microfabricated sensor to measure thermal conductivity of
      picoliter scale liquid samples.
AB  - This paper presents a thermal analysis device, which can measure thermal
      conductivity of picoliter scale liquid sample. We employ the three omega method
      with a microfabricated AC thermal sensor with nanometer width heater. The liquid
      sample is confined by a micro-well structure fabricated on the sensor surface.
      The performance of the instrument was verified by measuring the thermal
      conductivity of 27-picoliter samples of de-ionized (DI) water, ethanol, methanol,
      and DI water-ethanol mixtures with accuracies better than 3%. Furthermore,
      another analytical scheme allows real-time thermal conductivity measurement with
      5% accuracy. To the best of our knowledge, this technique requires the smallest
      volume of sample to measure thermal property ever.

PMID- 23126817
TI  - Note: Laser Doppler velocimeter using a dual-longitudinal-mode laser source.
AB  - This paper presents a new laser Doppler technique using a dual-longitudinal-mode
      He-Ne laser as the laser source. Theoretical analysis shows that the Doppler
      frequency is proportional with the frequency difference of the two modes. The
      Doppler frequency in this technique is very low compared with the one in the
      single-mode laser Doppler technique. The new laser Doppler technique can be used
      to measure high speed. Experiment results show that the Doppler frequency is only
      about 82 Hz while the measurement speed reaches 31.4 m/s. The signal-to-noise
      ratio of the Doppler signal is improved by the technique of digital filter and
      digital autocorrelation.

PMID- 23126818
TI  - Note: Comparison of grazing incidence small angle x-ray scattering of a titania
      sponge structure at the beamlines BW4 (DORIS III) and P03 (PETRA III).
AB  - Grazing incidence small angle x-ray scattering (GISAXS) is a powerful technique
      for morphology investigation of nanostructured thin films. GISAXS measurements at
      the newly installed P03 beamline at the storage ring PETRA III in Hamburg,
      Germany, are compared to the GISAXS data from the beamline BW4 at the storage
      ring DORIS III, which had been used extensively for GISAXS investigations in the
      past. As an example, a titania thin film sponge structure is investigated.
      Compared to BW4, at beamline P03 the resolution of larger structures is slightly
      improved and a higher incident flux leads to a factor of 750 in scattered
      intensity. Therefore, the acquisition time in GISAXS geometry is reduced
      significantly at beamline P03.

PMID- 23126819
TI  - Note: Development of 9 A current source for precise resistance measurement
      method.
AB  - In this Note, design of voltage controlled current source intended to be used in
      precise resistance measurement system in the range from 0.1 mOmega to 10 Omega is
      presented. The design specifications of current source include gross-tuning of
      current in the range from 0.1 mA to 9 A, low noise, low temperature coefficient,
      and short term stability better than 50 ppm. The realized current source has
      achieved better short term stability than comparable commercial devices.

PMID- 23126820
TI  - Note: 15-fs, 15-MUJ green pulses from two-stage temporal compressor of ytterbium
      laser pulses.
AB  - 15-fs, 15-MUJ light pulses at the central wavelength of 515 nm were generated by
      two-stage nonlinear compression of 300-fs, 150-MUJ ytterbium laser pulses. The
      compression was based on the pulse spectrum broadening by self-phase modulation
      in gas filled capillary and second harmonic generation in crystal.

PMID- 23126821
TI  - Note: Particle adhesion and imaging of particle/surface breakage zone.
AB  - An AFM methodology to enable measurement of the adhesion of micrometre sized
      objects, having contact areas in the range of nanometre to micrometer, is
      reported. The method also enables imaging of the actual breakage zone on both the
      surface and the removed object to obtain further information regarding the
      breakage zone. The method is also useful for measuring consolidating systems,
      such as drying, curing, or annealing systems.

PMID- 23126822
TI  - Note: Controlled fabrication of suspended metallic vacuum tunneling gaps.
AB  - We developed a new fabrication technique for the realization of nanogaps using
      conventional lithography and in situ controlled thermal evaporation. A 20-40 nm
      gap between two suspended metallic electrodes is shrunk down to about 1 nm using
      controlled thermal evaporation. It is demonstrated that with this technique rigid
      and stable metallic vacuum tunneling junctions can be consistently produced. The
      fabricated nanogaps were characterized by I-V measurements and their gap sizes
      and barrier heights were interrogated using the Simmons' model.

PMID- 23126823
TI  - Note: Axially pull-up electrochemical etching method for fabricating tungsten
      nanoprobes with controllable aspect ratio.
AB  - A mathematical model representing the relation between pulling up speed, time and
      aspect ratio is reported, accordingly the axially pull-up electrochemical etching
      method for fabricating nanoprobes is proposed. The tungsten probes with
      predetermined shape and aspect ratio according to the model were successfully
      produced with this method. Then the probes were installed inside a
      micromanipulation system to manipulate the carbon nanotubes and measure their
      current-voltage (I-V) characteristics. The probe fabrication and application
      experiments demonstrated the reasonability and reliability of the model and
      method developed in this note.

PMID- 23126824
TI  - Comment on "Elastic incoherent neutron scattering operating by varying
      instrumental energy resolution: Principle, simulations, and experiments of the
      resolution elastic neutron scattering (RENS)" [Rev. Sci. Instrum. 82, 105115
      (2011)].
AB  - In a recent contribution to this journal, Magazu, Migliardo, and Benedetto
      suggest to determine relaxation times from inflection points in the elastic
      neutron scattering intensity as function of (1) resolution time or (2)
      temperature. Method (1) can be generalized into a scaling law. Method (2) is only
      approximately valid; its application to protein data does not back a wavenumber
      independent dynamic transition.

PMID- 23126828
TI  - Ultra-high speed photomultiplier tubes with nanosecond gating for fusion
      diagnostics.
AB  - Fusion diagnostics can involve the measurement of ultra-fast optical pulses,
      often in close temporal proximity. We present a solution for the diagnostics of
      gamma reaction history and neutron time of flight by using microchannel plate
      based photomultiplier tubes (PMTs). The time response of the PMTs can be as fast
      as 100 ps FWHM and with a gain of up to 10(7). To observe small events in close
      temporal proximity to much larger signals such as the down-scattered fraction,
      the response of MCP-PMTs can be gated with an on/off ratio of up to 10(13) in
      just 2 ns.

PMID- 23126829
TI  - Time-resolved ion energy distribution measurements using an advanced neutral
      particle analyzer on the MST reversed-field pinch.
AB  - An advanced neutral particle analyzer (ANPA) capable of simultaneously measuring
      hydrogen and deuterium ions of energies up to 45 keV has recently been developed
      for use on the Madison Symmetric Torus. The charge-to-mass separation allows for
      separate analysis of bulk deuterium ions and hydrogen ions injected with a 1 MW,
      25 keV neutral beam. Orientation of the ANPA allows sampling of different regions
      of ion velocity space; a radial viewport favors collection of ions with high
      v(perpendicular)/|v| while a recently installed tangential viewport favors ions
      with high v(||)/|v|, such as those from the core-localized fast ion population
      created by the neutral beam. Signals are observed in the ANPA's highest energy
      channels during periodic magnetic reconnection events, which are drivers of
      anisotropic, non-Maxwellian ion energization in the reversed-field pinch. ANPA
      signal strength is dependent on the background neutral density, which also
      increases during magnetic reconnection events, so careful analysis must be
      performed to identify the true change in the ion distribution. A Monte Carlo
      neutral particle tracing code (NENE) is used to reconstruct neutral density
      profiles based on D(alpha) line emission, which is measured using a 16-chord
      filtered photodiode array.

PMID- 23126830
TI  - Development of the prototype pneumatic transfer system for ITER neutron
      activation system.
AB  - The neutron activation system (NAS) measures neutron fluence at the first wall
      and the total neutron flux from the ITER plasma, providing evaluation of the
      fusion power for all operational phases. The pneumatic transfer system (PTS) is
      one of the key components of the NAS for the proper operation of the system,
      playing a role of transferring encapsulated samples between the capsule loading
      machine, irradiation stations, counting stations, and disposal bin. For the
      validation and the optimization of the design, a prototype of the PTS was
      developed and capsule transfer tests were performed with the developed system.

PMID- 23126831
TI  - Compact solid-state neutral particle analyzer in current mode.
AB  - Solid state neutral particle analyzer (ssNPA) arrays are operated in current mode
      on the DIII-D tokamak and the National Spherical Torus Experiment (NSTX).
      Compared with conventional pulse-counting NPAs, current-mode operation sacrifices
      energy resolution to obtain economical, high-bandwidth, pitch-angle resolved
      measurements. With the success from a new three-channel near-vertical-view
      current mode ssNPA on DIII-D, the apertures on an existing array on NSTX were
      expanded to increase the particle influx. The sightlines of both arrays intersect
      heating beams, enabling both active and passive charge exchange measurements. The
      spatial resolution at beam intersection is typically 5 cm on both devices.
      Directly deposited ultra-thin foils on the detector surface block stray photons
      below the energy of 1 keV and also set low energy threshold about 25 keV for
      deuterium particle detection. Oscillations in neutral flux produced by high
      frequency magnetohydrodynamics (MHD) instabilities are readily detected.

PMID- 23126832
TI  - Initial measurements of fast ion loss in KSTAR.
AB  - A fast ion loss detector (FILD) has been installed and tested in Korea
      Superconducting Tokamak Advanced Research (KSTAR). KSTAR FILD measures the energy
      and the pitch-angle of the escaping ions with the striking positions on the
      scintillator plane. Measurements of the fast ion loss have been performed for the
      neutral beam heated plasmas. Initial experimental results indicate the prompt
      losses from neutral beam are dominant and the effects of the resonant magnetic
      perturbation on the fast ion loss are investigated. In addition, further design
      change of the detector-head in order to avoid excessive heat load and to detect
      the fusion products or the fast ions having order of MeV of energy is also
      discussed.

PMID- 23126833
TI  - Investigating the performance of an ion luminescence probe as a multichannel fast
      ion energy spectrometer using pulse height analysis.
AB  - We investigate the capability of a fast-ion luminescent probe to operate as a
      pulse height ion energy analyzer. An existing high sensitivity system has been
      reconfigured as a single channel ion detector with an amplifier to give a
      bandwidth comparable to the phosphor response time. A digital pulse processing
      method has been developed to determine pulse heights from the detector signal so
      as to obtain time-resolved information on the ion energy distribution of the
      plasma ions lost to the wall of the TJ-II stellarator. Finally, the potential of
      this approach for magnetic confined fusion plasmas is evaluated by studying
      representative TJ-II discharges.

PMID- 23126834
TI  - X-ray bang-time and fusion reaction history at picosecond resolution using
      RadOptic detection.
AB  - We report recent progress in the development of RadOptic detectors, radiation to
      optical converters, that rely upon x-ray absorption induced modulation of the
      optical refractive index of a semiconductor sensor medium to amplitude modulate
      an optical probe beam. The sensor temporal response is determined by the dynamics
      of the electron-hole pair creation and subsequent relaxation in the sensor
      medium. Response times of a few ps have been demonstrated in a series of
      experiments conducted at the LLNL Jupiter Laser Facility (JLF). This technology
      will enable x-ray bang-time and fusion burn-history measurements with ~ ps
      resolution.

PMID- 23126836
TI  - Testing a new NIF neutron time-of-flight detector with a bibenzyl scintillator on
      OMEGA.
AB  - A new neutron time-of-flight (nTOF) detector with a bibenzyl crystal as a
      scintillator has been designed and manufactured for the National Ignition
      Facility (NIF). This detector will replace a nTOF20-Spec detector with an
      oxygenated xylene scintillator currently operational on the NIF to improve the
      areal-density measurements. In addition to areal density, the bibenzyl detector
      will measure the D-D and D-T neutron yield and the ion temperature of indirect-
      and direct-drive-implosion experiments. The design of the bibenzyl detector and
      results of tests on the OMEGA Laser System are presented.

PMID- 23126837
TI  - Comparisons of NIF convergent ablation simulations with radiograph data.
AB  - A technique for comparing simulation results directly with radiograph data from
      backlit capsule implosion experiments will be discussed. Forward Abel transforms
      are applied to the kappa*rho profiles of the simulation. These provide the
      transmission ratio (optical depth) profiles of the simulation. Gaussian and top
      hat blurs are applied to the simulated transmission ratio profiles in order to
      account for the motion blurring and imaging slit resolution of the experimental
      measurement. Comparisons between the simulated transmission ratios and the
      radiograph data lineouts are iterated until a reasonable backlighter profile is
      obtained. This backlighter profile is combined with the blurred, simulated
      transmission ratios to obtain simulated intensity profiles that can be directly
      compared with the radiograph data. Examples will be shown from recent convergent
      ablation (backlit implosion) experiments at the NIF.

PMID- 23126835
TI  - Neutron spectrometry--an essential tool for diagnosing implosions at the National
      Ignition Facility (invited).
AB  - DT neutron yield (Y(n)), ion temperature (T(i)), and down-scatter ratio (dsr)
      determined from measured neutron spectra are essential metrics for diagnosing the
      performance of inertial confinement fusion (ICF) implosions at the National
      Ignition Facility (NIF). A suite of neutron-time-of-flight (nTOF) spectrometers
      and a magnetic recoil spectrometer (MRS) have been implemented in different
      locations around the NIF target chamber, providing good implosion coverage and
      the complementarity required for reliable measurements of Y(n), T(i), and dsr.
      From the measured dsr value, an areal density (rhoR) is determined through the
      relationship rhoR(tot) (g/cm(2)) = (20.4 +/- 0.6) * dsr(10-12 MeV). The
      proportionality constant is determined considering implosion geometry, neutron
      attenuation, and energy range used for the dsr measurement. To ensure high
      accuracy in the measurements, a series of commissioning experiments using
      exploding pushers have been used for in situ calibration of the as-built
      spectrometers, which are now performing to the required accuracy. Recent data
      obtained with the MRS and nTOFs indicate that the implosion performance of
      cryogenically layered DT implosions, characterized by the experimental ignition
      threshold factor (ITFx), which is a function of dsr (or fuel rhoR) and Y(n), has
      improved almost two orders of magnitude since the first shot in September, 2010.

PMID- 23126838
TI  - Gamma-to-electron magnetic spectrometer (GEMS): an energy-resolved gamma-ray
      diagnostic for the National Ignition Facility.
AB  - The gamma-to-electron magnetic spectrometer, having better than 5% energy
      resolution, is proposed to resolve gamma-rays in the range of E(o) +/- 20% in
      single shot, where E(o) is the central energy and is tunable from 2 to 25 MeV.
      Gamma-rays from inertial confinement fusion implosions interact with a thin
      Compton converter (e.g., beryllium) located at approximately 300 cm from the
      target chamber center (TCC). Scattered electrons out of the Compton converter
      enter an electromagnet placed outside the NIF chamber (approximately 600 cm from
      TCC) where energy selection takes place. The electromagnet provides tunable E(o)
      over a broad range in a compact manner. Energy resolved electrons are measured by
      an array of quartz Cherenkov converters coupled to photomultipliers. Given 100
      detectable electrons in the energy bins of interest, 3 * 10(14) minimum
      deuterium/tritium (DT) neutrons will be required to measure the 4.44 MeV (12)C
      gamma-rays assuming 200 mg/cm(2) plastic ablator areal density and 3 * 10(15)
      minimum DT neutrons to measure the 16.75 MeV DT gamma-ray line.

PMID- 23126839
TI  - Deuterium-tritium neutron yield measurements with the 4.5 m neutron-time-of
      flight detectors at NIF.
AB  - The first several campaigns of laser fusion experiments at the National Ignition
      Facility (NIF) included a family of high-sensitivity scintillator/photodetector
      neutron-time-of-flight (nTOF) detectors for measuring deuterium-deuterium (DD)
      and DT neutron yields. The detectors provided consistent neutron yield (Y(n))
      measurements from below 10(9) (DD) to nearly 10(15) (DT). The detectors initially
      demonstrated detector-to-detector Y(n) precisions better than 5%, but lacked in
      situ absolute calibrations. Recent experiments at NIF now have provided in situ
      DT yield calibration data that establish the absolute sensitivity of the 4.5 m
      differential tissue harmonic imaging (DTHI) detector with an accuracy of +/- 10%
      and precision of +/- 1%. The 4.5 m nTOF calibration measurements also have helped
      to establish improved detector impulse response functions and data analysis
      methods, which have contributed to improving the accuracy of the Y(n)
      measurements. These advances have also helped to extend the usefulness of nTOF
      measurements of ion temperature and downscattered neutron ratio (neutron yield 10
      12 MeV divided by yield 13-15 MeV) with other nTOF detectors.

PMID- 23126840
TI  - Neutron activation diagnostics at the National Ignition Facility (invited).
AB  - Neutron yields are measured at the National Ignition Facility (NIF) by an
      extensive suite of neutron activation diagnostics. Neutrons interact with
      materials whose reaction cross sections threshold just below the fusion neutron
      production energy, providing an accurate measure of primary unscattered neutrons
      without contribution from lower-energy scattered neutrons. Indium samples are
      mounted on diagnostic instrument manipulators in the NIF target chamber, 25-50 cm
      from the source, to measure 2.45 MeV deuterium-deuterium fusion neutrons through
      the (115)In(n,n')(115 m) In reaction. Outside the chamber, zirconium and copper
      are used to measure 14 MeV deuterium-tritium fusion neutrons via (90)Zr(n,2n),
      (63)Cu(n,2n), and (65)Cu(n,2n) reactions. An array of 16 zirconium samples are
      located on port covers around the chamber to measure relative yield anisotropies,
      providing a global map of fuel areal density variation. Neutron yields are
      routinely measured with activation to an accuracy of 7% and are in excellent
      agreement both with each other and with neutron time-of-flight and magnetic
      recoil spectrometer measurements. Relative areal density anisotropies can be
      measured to a precision of less than 3%. These measurements reveal apparent bulk
      fuel velocities as high as 200 km/s in addition to large areal density variations
      between the pole and equator of the compressed fuel.

PMID- 23126841
TI  - Enhanced NIF neutron activation diagnostics.
AB  - The NIF neutron activation diagnostic suite relies on removable activation
      samples, leading to operational inefficiencies and a fundamental lower limit on
      the half-life of the activated product that can be observed. A neutron diagnostic
      system measuring activation of permanently installed samples could remove these
      limitations and significantly enhance overall neutron diagnostic capabilities.
      The physics and engineering aspects of two proposed systems are considered: one
      measuring the (89)Zr/(89 m)Zr isomer ratio in the existing Zr activation medium
      and the other using potassium zirconate as the activation medium. Both proposed
      systems could improve the signal-to-noise ratio of the current system by at least
      a factor of 5 and would allow independent measurement of fusion core velocity and
      fuel areal density.

PMID- 23126842
TI  - Simultaneous usage of pinhole and penumbral apertures for imaging small scale
      neutron sources from inertial confinement fusion experiments.
AB  - Inertial confinement fusion experiments at the National Ignition Facility are
      designed to understand the basic principles of creating self-sustaining fusion
      reactions by laser driven compression of deuterium-tritium (DT) filled cryogenic
      plastic capsules. The neutron imaging diagnostic provides information on the
      distribution of the central fusion reaction region and the surrounding DT fuel by
      observing neutron images in two different energy bands for primary (13-17 MeV)
      and down-scattered (6-12 MeV) neutrons. From this, the final shape and size of
      the compressed capsule can be estimated and the symmetry of the compression can
      be inferred. These experiments provide small sources with high yield neutron
      flux. An aperture design that includes an array of pinholes and penumbral
      apertures has provided the opportunity to image the same source with two
      different techniques. This allows for an evaluation of these different aperture
      designs and reconstruction algorithms.

PMID- 23126843
TI  - The neutron imaging diagnostic at NIF (invited).
AB  - A neutron imaging diagnostic has recently been commissioned at the National
      Ignition Facility (NIF). This new system is an important diagnostic tool for
      inertial fusion studies at the NIF for measuring the size and shape of the
      burning DT plasma during the ignition stage of Inertial Confinement Fusion (ICF)
      implosions. The imaging technique utilizes a pinhole neutron aperture, placed
      between the neutron source and a neutron detector. The detection system measures
      the two dimensional distribution of neutrons passing through the pinhole. This
      diagnostic has been designed to collect two images at two times. The long flight
      path for this diagnostic, 28 m, results in a chromatic separation of the
      neutrons, allowing the independently timed images to measure the source
      distribution for two neutron energies. Typically the first image measures the
      distribution of the 14 MeV neutrons and the second image of the 6-12 MeV
      neutrons. The combination of these two images has provided data on the size and
      shape of the burning plasma within the compressed capsule, as well as a measure
      of the quantity and spatial distribution of the cold fuel surrounding this core.

PMID- 23126844
TI  - First fusion proton measurements in TEXTOR plasmas using activation technique.
AB  - MeV particle loss measurements from fusion plasmas, in particular alpha
      particles, remain difficult in large fusion devices and further R&D is needed for
      ITER. This paper describes the first attempt to measure 3 MeV escaping fusion
      protons emitted from TEXTOR tokamak plasmas using activation technique. This
      technique was successfully demonstrated, initially, in 2006 on the JET tokamak.
      An ion camera equipped with a collimator and several types of activation
      detectors was installed inside the TEXTOR vacuum vessel to perform these
      measurements. After irradiation, the detectors were analyzed using ultra low
      level gamma-ray spectrometry at the HADES underground laboratory. 3 MeV escaping
      fusion protons were detected in larger number -~6 times more--compared to earlier
      measurements using this technique on JET. Another major progress was the
      reduction of the cooling time by a factor of 50, which made possible to detect
      radionuclides with half-life of less than 90 min.

PMID- 23126845
TI  - Calculation of impurity poloidal rotation from measured poloidal asymmetries in
      the toroidal rotation of a tokamak plasma.
AB  - To improve poloidal rotation measurement capabilities on the DIII-D tokamak, new
      chords for the charge exchange recombination spectroscopy (CER) diagnostic have
      been installed. CER is a common method for measuring impurity rotation in tokamak
      plasmas. These new chords make measurements on the high-field side of the plasma.
      They are designed so that they can measure toroidal rotation without the need for
      the calculation of atomic physics corrections. Asymmetry between toroidal
      rotation on the high- and low-field sides of the plasma is used to calculate
      poloidal rotation. Results for the main impurity in the plasma are shown and
      compared with a neoclassical calculation of poloidal rotation.

PMID- 23126846
TI  - Diagnostic performance of the beam emission spectroscopy system on the National
      Spherical Torus Experiment.
AB  - The beam emission spectroscopy system on the National Spherical Torus Experiment
      measures localized density fluctuations on the ion gyroscale. Optical sightlines
      provide core to edge radial coverage, and the sightlines are aligned to typical
      pitch angles to maximize cross-field spatial resolution. Sightline images are 2-3
      cm, and point spread function calculations indicate image distortion from pitch
      angle misalignment and atomic state finite lifetimes is minor with a 15% increase
      in the image size. New generation photodetectors achieve photon noise limited
      measurements at frequencies up to 400 kHz with refrigerant cooling at -20 
      degrees C. Measurements near the pedestal show broadband turbulence up to 100
      kHz, and poloidal correlation lengths are about 10 cm. Plasma turbulence signals
      can be 2-3 orders of magnitude above photon noise and amplifier thermal noise.

PMID- 23126847
TI  - Magnetic field measurements in low density plasmas using paramagnetic Faraday
      rotator glass.
AB  - Paramagnetic Faraday rotator glass (rare-earth doped borosilicate) with a high
      Verdet constant will be used to measure the magnetic field inside of low density
      Helium plasmas (T(e) ~ 5 eV, T(i) ~ 1 eV) with a density of n ~ 10(12) cm(-3).
      Linearly polarized light is sent through the glass such that the plane of
      polarization is rotated by an angle that depends on the strength of the magnetic
      field in the direction of propagation and the length of the crystal (6 mm). The
      light is then passed into an analyzer and photo-detector setup to determine the
      change in polarization angle. This setup can detect magnetic fields up to 5 kG
      with a resolution of <5 G and a temporal resolution on the order of a nanosecond.
      The diagnostic will be used to characterize the structure and evolution of laser
      driven collisionless shocks in large magnetized plasmas.

PMID- 23126848
TI  - A non-statistical atomic model for beam emission and motional Stark effect
      diagnostics in fusion plasmas.
AB  - In this work we analyze magnetic sublevel populations in a neutral beam
      penetrating a fusion plasma. The collisional-radiative model NOMAD was extended
      to include magnetic parabolic sublevels with principal quantum numbers n <= 10.
      The collisional parameters were calculated with the advanced atomic-orbital close
      coupling method and the Glauber approximation. The ionization by the induced
      electric field was also included in the model. The results of our calculations
      show significant deviations of the sublevel populations and, accordingly, line
      intensities of the sigma and pi components, from the statistical approximation.
      It is shown, for instance, that for a number of experimental conditions the total
      intensity of sigma components is not equal to the total intensity of pi
      components, which has a strong effect on determination of magnetic field and
      pitch angle in fusion devices. The results are presented for a wide range of
      plasma and beam parameters. The most significant deviations are observed for
      strong magnetic fields and high beam energies typical for the ITER plasma, where
      component intensity ratios may deviate by more than 20% from the statistical
      values.

PMID- 23126849
TI  - High resolution ion Doppler spectroscopy at Prairie View Rotamak.
AB  - A fast ion Doppler spectroscopy (IDS) diagnostic system is installed on the
      Prairie View Rotamak to measure ion temperature and plasma flow. The diagnostic
      employs a single channel photomultiplier tube and a Jarrell-Ash 50 monochromator
      with a diffraction grating line density of 1180 lines/mm, which allows for first
      order spectra of 200-600 nm. The motorized gear of the monochromator allows
      spectral resolution of 0.01 nm. Equal IDS measurements are observed for various
      impurity emission lines of which carbon lines exhibit stronger intensities.
      Furthermore, the diagnostics is examined in an experiment where plasma
      experiences sudden disruption and quick recovery. In this case, the IDS
      measurements show ~130% increase in ion temperature. Flow measurements are shown
      to be consistent with plasma rotation.

PMID- 23126850
TI  - Absolute sensitivity calibration of vacuum and extreme ultraviolet spectrometer
      systems and Z(eff) measurement based on bremsstrahlung continuum in HL-2A
      tokamak.
AB  - A grazing-incidence flat-field extreme ultraviolet (EUV) spectrometer has been
      newly developed in HL-2A tokamak. Typical spectral lines are observed from
      intrinsic impurities of carbon, oxygen, iron, and extrinsic impurity of helium in
      the wavelength range of 20 A-500 A. Bremsstrahlung continuum is measured at
      different electron densities of HL-2A discharges to calibrate absolute
      sensitivity of the EUV spectrometer system and to measure effective ionic charge,
      Z(eff). The sensitivity of a vacuum ultraviolet (VUV) spectrometer system is also
      absolutely calibrated in overlapped wavelength range of 300 A-500 A by comparing
      the intensity between VUV and EUV line emissions.

PMID- 23126851
TI  - Comparison of collisional radiative models for edge electron density
      reconstruction from Li I (2s-2p) emission profiles.
AB  - Four collisional radiative models (CRMs) for reconstruction of the edge electron
      density profile from the measured Li I (2s-2p) emission profile of an accelerated
      lithium beam are compared using experimental data from DIII-D. It is shown for
      both L- and H-mode plasmas that edge density profiles reconstructed with the CRMs
      DDD2, ABSOLUT, [Sasaki et al. Rev. Sci. Instrum. 64, 1699 (1993)] and a new model
      developed at DIII-D agree in a density scan from n(e) (ped) = (2.0-6.5) * 10(19)
      m(-3) within 20%, 20%, <5%, and 40%, respectively, of the pedestal density
      measured with Thomson scattering. Profile shape and absolute density vary in a
      scan of the effective ion charge Z(eff) = 1-6 up to a factor of two but agree
      with Thomson data for Z(eff) = 1-2 within the error bars.

PMID- 23126852
TI  - Effect of high-energy neutral particles on extreme ultraviolet spectroscopy in
      large helical device.
AB  - Spectra measured by an extreme ultraviolet (EUV) spectrometer frequently suffer
      large spike noise when Large Helical Device is operated in low-density range (<=
      3 * 10(13) cm(-3)) with neutral beam injection (NBI). The spike noise completely
      disappears in electron cyclotron heating discharges. In order to examine the
      effect of NBI, a carbon filter with thickness of 150 nm was installed in the EUV
      spectrometer. As a result, the spike noise was reduced by an order of magnitude.
      It is experimentally verified that the spike noise is caused by escaping high
      energy neutral particles resulting from the circulating high-energy hydrogen ions
      borne from NBI.

PMID- 23126853
TI  - Spatial heterodyne Stokes vector imaging of the motional Stark-Zeeman multiplet.
AB  - We present a general Stokes interferometer/polarimeter suitable for polarimetric
      imaging the elliptically polarized motional Stark-Zeeman multiplet. We also
      introduce a fully phase-heterodyne spatial multiplex variant of the system that
      has been used for imaging of Balmer alpha emission from the heating neutral beam
      in the KSTAR super-conducting tokamak in Korea. The polarimeter performance is
      illustrated using various polarization test targets.

PMID- 23126854
TI  - Simultaneous imaging/reflectivity measurements to assess diagnostic mirror
      cleaning.
AB  - Practical methods to clean ITER's diagnostic mirrors and restore reflectivity
      will be critical to ITER's plasma operations. We describe a technique to assess
      the efficacy of mirror cleaning techniques and detect any damage to the mirror
      surface. The method combines microscopic imaging and reflectivity measurements in
      the red, green, and blue spectral regions and at selected wavelengths. The method
      has been applied to laser cleaning of single crystal molybdenum mirrors coated
      with either carbon or beryllium films 150-420 nm thick. It is suitable for
      hazardous materials such as beryllium as the mirrors remain sealed in a vacuum
      chamber.

PMID- 23126855
TI  - Improved spectral analysis for the motional Stark effect diagnostic.
AB  - The magnetic pitch angle and the magnitude from reversed field pinch plasmas in
      the Madison symmetric torus (MST) have been routinely obtained from fully
      resolved motional Stark effect (MSE) spectrum analyses. Recently, the spectrum
      fit procedure has been improved by initializing and constraining the fit
      parameters based on the MSE model in the atomic data and analysis structure. A
      collisional-radiative model with level populations nlm-resolved up to n = 4 and a
      simple Born approximation for ion-impact cross sections is used for this
      analysis. Measurement uncertainty is quantified by making MSE measurements with
      multiple views of a single spatial location, ranging 5%-15% for typical MST
      operation conditions. A multi-view fit improves the goodness of fit of MSE
      spectral features and background.

PMID- 23126856
TI  - Optical pyrometer system for collisionless shock experiments in high-power laser
      produced plasmas.
AB  - A temporally and spatially resolved optical pyrometer system has been fielded on
      Gekko XII experiments. The system is based on the self-emission measurements with
      a gated optical imager (GOI) and a streaked optical pyrometer (SOP). Both
      detectors measure the intensity of the self-emission from laser-produced plasmas
      at the wavelength of 450 nm with a bandpass filter with a width of ~10 nm in
      FWHM. The measurements were calibrated with different methods, and both results
      agreed with each other within 30% as previously reported [T. Morita et al.,
      Astrophys. Space Sci. 336, 283 (2011)]. As a tool for measuring the properties of
      low-density plasmas, the system is applicable for the measurements of the
      electron temperature and density in collisionless shock experiments [Y. Kuramitsu
      et al., Phys. Rev. Lett. 106, 175002 (2011)].

PMID- 23126857
TI  - A high etendue spectrometer suitable for core charge eXchange recombination
      spectroscopy on ITER.
AB  - A feasibility study for the use of core charge exchange recombination
      spectroscopy on ITER has shown that accurate measurements on the helium ash
      require a spectrometer with a high etendue of 1mm(2)sr to comply with the
      measurement requirements [S. Tugarinov et al., Rev. Sci. Instrum. 74, 2075
      (2003)]. To this purpose such an instrument has been developed consisting of
      three separate wavelength channels (to measure simultaneously He/Be, C/Ne, and
      H/D/T together with the Doppler shifted direct emission of the diagnostic neutral
      beam, the beam emission (BES) signal), combining high dispersion (0.02 nm/pixel),
      sufficient resolution (0.2 nm), high efficiency (55%), and extended wavelength
      range (14 nm) at high etendue. The combined measurement of the BES along the same
      sightline within a third wavelength range provides the possibility for in situ
      calibration of the charge eXchange recombination spectroscopy signals. In
      addition, the option is included to use the same instrument for measurements of
      the fast fluctuations of the beam emission intensity up to 2 MHz, with the aim to
      study MHD activity.

PMID- 23126858
TI  - Multi-point, high-speed passive ion velocity distribution diagnostic on the
      Pegasus Toroidal Experiment.
AB  - A passive ion temperature polychromator has been deployed on Pegasus to study
      power balance and non-thermal ion distributions that arise during point source
      helicity injection. Spectra are recorded from a 1 m F/8.6 Czerny-Turner
      polychromator whose output is recorded by an intensified high-speed camera. The
      use of high orders allows for a dispersion of 0.02 A/mm in 4th order and a
      bandpass of 0.14 A (~13 km/s) at 3131 A in 4th order with 100 MUm entrance slit.
      The instrument temperature of the spectrometer is 15 eV. Light from the output of
      an image intensifier in the spectrometer focal plane is coupled to a high-speed
      CMOS camera. The system can accommodate up to 20 spatial points recorded at 0.5
      ms time resolution. During helicity injection, stochastic magnetic fields keep
      T(e) low (100 eV) and thus low ionization impurities penetrate to the core. Under
      these conditions, high core ion temperatures are measured (T(i) ~ 1.2 keV, T(e) ~
      0.1 keV) using spectral lines from carbon III, nitrogen III, and boron IV.

PMID- 23126859
TI  - Determination of neutral beam energy fractions from collisional radiative
      measurements on DIII-D.
AB  - Neutral beams based on positive ion source technology are a key component of
      contemporary fusion research. An accurate assessment of the injected beam species
      mix is important for determining the actual plasma heating and momentum input as
      well as proper interpretation of beam-based diagnostics. On DIII-D, the main ion
      charge-exchange spectroscopy system is used to extract well-resolved intensity
      ratios of the Doppler-shifted D(alpha) emission from the full, half, and third
      energy beam components for a variety of beam operational parameters. In
      conjunction with accurate collisional-radiative modeling, these measurements
      indicate the assumed species mix and power fractions can vary significantly and
      should be regularly monitored and updated for the most accurate interpretation of
      plasma performance. In addition, if stable active control of the power fractions
      can be achieved through appropriate source tuning, the resulting control over the
      deposition profile can serve as an additional experimental knob for advanced
      tokamak studies, e.g., varying the off axis beam current drive without altering
      the beam trajectory.

PMID- 23126860
TI  - Method to obtain absolute impurity density profiles combining charge exchange and
      beam emission spectroscopy without absolute intensity calibration.
AB  - Investigation of impurity transport properties in tokamak plasmas is essential
      and a diagnostic that can provide information on the impurity content is
      required. Combining charge exchange recombination spectroscopy (CXRS) and beam
      emission spectroscopy (BES), absolute radial profiles of impurity densities can
      be obtained from the CXRS and BES intensities, electron density and CXRS and BES
      emission rates, without requiring any absolute calibration of the spectra. The
      technique is demonstrated here with absolute impurity density radial profiles
      obtained in TEXTOR plasmas, using a high efficiency charge exchange spectrometer
      with high etendue, that measures the CXRS and BES spectra along the same lines-of
      sight, offering an additional advantage for the determination of absolute
      impurity densities.

PMID- 23126861
TI  - High-resolution time-resolved extreme ultraviolet spectroscopy on NSTX.
AB  - We report on upgrades to the flat-field grazing-incidence grating spectrometers X
      ray and Extreme Ultraviolet Spectrometer (XEUS) and Long-Wavelength Extreme
      Ultraviolet Spectrometer (LoWEUS), at the National Spherical Torus Experiment
      (NSTX) at the Princeton Plasma Physics Laboratory. XEUS employs a variable space
      grating with an average spacing of 2400 lines/mm and covers the 9-64 A wavelength
      band, while LoWEUS has an average spacing of 1200 lines/mm and is positioned to
      monitor the 90-270 A wavelength band. Both spectrometers have been upgraded with
      new cameras that achieve 12.5 ms time resolution. We demonstrate the new time
      resolution capability by showing the time evolution of iron in the NSTX plasma.

PMID- 23126862
TI  - Divertor electron temperature and impurity diffusion measurements with a
      spectrally resolved imaging radiometer.
AB  - A divertor imaging radiometer (DIR) diagnostic is being studied to measure
      spatially and spectrally resolved radiated power P(rad)(lambda) in the tokamak
      divertor. A dual transmission grating design, with extreme ultraviolet (~20-200
      A) and vacuum ultraviolet (~200-2000 A) gratings placed side-by-side, can produce
      coarse spectral resolution over a broad wavelength range covering emission from
      impurities over a wide temperature range. The DIR can thus be used to evaluate
      the separate P(rad) contributions from different ion species and charge states.
      Additionally, synthetic spectra from divertor simulations can be fit to
      P(rad)(lambda) measurements, providing a powerful code validation tool that can
      also be used to estimate electron divertor temperature and impurity transport.

PMID- 23126863
TI  - Multi-chord fiber-coupled interferometry of supersonic plasma jets (invited).
AB  - A multi-chord fiber-coupled interferometer is being used to make time-resolved
      density measurements of supersonic argon plasma jets on the Plasma Liner
      Experiment. The long coherence length of the laser (>10 m) allows signal and
      reference path lengths to be mismatched by many meters without signal
      degradation, making for a greatly simplified optical layout. Measured
      interferometry phase shifts are consistent with a partially ionized plasma in
      which both positive and negative phase shift values are observed depending on the
      ionization fraction. In this case, both free electrons and bound electrons in
      ions and neutral atoms contribute to the index of refraction. This paper
      illustrates how the interferometry data, aided by numerical modeling, are used to
      derive total jet density, jet propagation velocity (~15-50 km/s), jet length (~20
      100 cm), and 3D expansion.

PMID- 23126864
TI  - Real-time MSE measurements for current profile control on KSTAR.
AB  - To step up from current day fusion experiments to power producing fusion
      reactors, it is necessary to control long pulse, burning plasmas. Stability and
      confinement properties of tokamak fusion reactors are determined by the current
      or q profile. In order to control the q profile, it is necessary to measure it in
      real-time. A real-time motional Stark effect diagnostic is being developed at
      Korean Superconducting Tokamak for Advanced Research for this purpose. This paper
      focuses on 3 topics important for real-time measurements: minimize the use of ad
      hoc parameters, minimize external influences and a robust and fast analysis
      algorithm. Specifically, we have looked into extracting the retardance of the
      photo-elastic modulators from the signal itself, minimizing the influence of
      overlapping beam spectra by optimizing the optical filter design and a multi
      channel, multiharmonic phase locking algorithm.

PMID- 23126865
TI  - Examinations of electron temperature calculation methods in Thomson scattering
      diagnostics.
AB  - Electron temperature from Thomson scattering diagnostic is derived through
      indirect calculation based on theoretical model. chi-square test is commonly used
      in the calculation, and the reliability of the calculation method highly depends
      on the noise level of input signals. In the simulations, noise effects of the chi
      square test are examined and scale factor test is proposed as an alternative
      method.

PMID- 23126866
TI  - Ultra-fast charge exchange spectroscopy for turbulent ion temperature fluctuation
      measurements on the DIII-D tokamak (invited).
AB  - A novel two-channel, high throughput, high efficiency spectrometer system has
      been developed to measure impurity ion temperature and toroidal velocity
      fluctuations associated with long-wavelength turbulence and other plasma
      instabilities. The spectrometer observes the emission of the n = 8-7 hydrogenic
      transition of C(+5) ions (lambda(air) = 529.06 nm) resulting from charge exchange
      reactions between deuterium heating beams and intrinsic carbon. Novel features
      include a large, prism-coupled high-dispersion, volume-phase-holographic
      transmission grating and high-quantum efficiency, high-gain, low-noise avalanche
      photodiode detectors that sample emission at 1 MHz. This new diagnostic offers an
      order-of-magnitude increase in sensitivity compared to earlier ion thermal
      turbulence measurements. Increased sensitivity is crucial for obtaining enough
      photon statistics from plasmas with much less impurity content. The irreducible
      noise floor set by photon statistics sets the ultimate sensitivity to plasma
      fluctuations. Based on the measured photon flux levels for the entire spectral
      line, photon noise levels for T(i)/T(i) and V(i)/V(i) of ~1% are expected, while
      statistical averaging over long data records enables reduction in the detectable
      plasma fluctuation levels to values less than that. Broadband ion temperature
      fluctuations are observed to near 200 kHz in an L-mode discharge. Cross
      correlation with the local beam emission spectroscopy measurements demonstrates a
      strong coupling of the density and temperature fields, and enables the cross
      phase measurements between density and ion temperature fluctuations.

PMID- 23126867
TI  - Radial resolution enhancement of the NSTX Thomson scattering diagnostic.
AB  - Current magnetic confinement plasma physics research has increased the demand for
      radial resolution in profile diagnostics, in particular in the edge and pedestal
      regions. On NSTX, an upgrade of the existing multi-point Thomson scattering
      diagnostic has been implemented in order to respond to the research program
      needs. Twelve new radial channels have been added bringing the total number of
      positions to 42. Four previously un-instrumented fiber bundles were put in
      service. Eight existing "active" fiber bundles were divided in two sub-bundles
      each in order to increase spatial resolution. Twelve radial channels now cover
      the pedestal region with a resolution near one centimeter. Fifteen radial
      channels cover the core and internal transport barrier regions. Two additional
      channels were added, one near the inner edge and one in the outer scrape-off
      layer. The intersection of the focused viewing optics field of view with a finite
      width laser beam results in major-radius cross talk between adjacent fiber sub
      bundles. A discussion and calculation of the cross talk will be presented.

PMID- 23126868
TI  - Hanle effect as candidate for measuring magnetic fields in laboratory plasmas.
AB  - Weak or turbulent magnetic fields are generally difficult to measure in
      laboratory plasmas. A new technique to address this problem may be based on the
      Hanle effect, used for magnetic field measurements in solar and stellar
      atmospheres. The effect consists in the modification of the polarization state of
      the resonance-line scattered radiation. It applies for magnetic field strengths
      for which the shift of magnetic sublevels remains comparable to the natural width
      of the sublevels. Experimental configurations and parameter ranges of
      applicability of a Hanle effect-based diagnostics technique are discussed.

PMID- 23126869
TI  - Active spectroscopic measurements of the bulk deuterium properties in the DIII-D
      tokamak (invited).
AB  - The neutral-beam induced D(alpha) emission spectrum contains a wealth of
      information such as deuterium ion temperature, toroidal rotation, density, beam
      emission intensity, beam neutral density, and local magnetic field strength
      magnitude |B| from the Stark-split beam emission spectrum, and fast-ion D(alpha)
      emission (FIDA) proportional to the beam-injected fast ion density. A
      comprehensive spectral fitting routine which accounts for all photoemission
      processes is employed for the spectral analysis. Interpretation of the
      measurements to determine physically relevant plasma parameters is assisted by
      the use of an optimized viewing geometry and forward modeling of the emission
      spectra using a Monte-Carlo 3D simulation code.

PMID- 23126870
TI  - Analysis of edge density fluctuation measured by trial KSTAR beam emission
      spectroscopy system.
AB  - A beam emission spectroscopy (BES) system based on direct imaging avalanche
      photodiode (APD) camera has been designed for Korea Superconducting Tokamak
      Advanced Research (KSTAR) and a trial system has been constructed and installed
      for evaluating feasibility of the design. The system contains two cameras, one is
      an APD camera for BES measurement and another is a fast visible camera for
      position calibration. Two pneumatically actuated mirrors were positioned at front
      and rear of lens optics. The front mirror can switch the measurement between edge
      and core region of plasma and the rear mirror can switch between the APD and the
      visible camera. All systems worked properly and the measured photon flux was
      reasonable as expected from the simulation. While the measurement data from the
      trial system were limited, it revealed some interesting characteristics of KSTAR
      plasma suggesting future research works with fully installed BES system. The
      analysis result and the development plan will be presented in this paper.

PMID- 23126871
TI  - Prospects for the Thomson scattering system on NSTX-Upgrade.
AB  - The paper discusses the projected configuration of the Thomson system on the
      National Spherical Torus Experiment (NSTX-U). In this paper, we discuss the
      projected configuration of the Thomson system on NSTX-U. More specifically, we
      determine, through both optical modeling of the collection optics and in-vessel
      measurements, that the collecting fibers are to be displaced by at most 1 cm
      toward the imaging plane along the optical axis. Finally, we estimate the
      performance of the Thomson system in measuring the electron temperature for NSTX
      U discharges.

PMID- 23126872
TI  - Measurements of neutral density profiles using a deuterium Balmer-alpha
      diagnostic in the C-2 FRC plasma.
AB  - In C-2 field-reversed configuration (FRC) device, low neutral density outside the
      FRC separatrix is required to minimize the charge exchange loss of fast
      particles. Titanium gettering is used in C-2 to reduce the wall recycling and
      keep the neutral density low in plasma edge. The measurements of neutral density
      radial profile are desirable to understand the plasma recycling and the effects
      of titanium gettering. These measurements are also needed to study the
      interaction of neutral beams with FRC plasma and confinement of fast ions.
      Diagnostic based on absolute deuterium Balmer-alpha (D-alpha) radiation
      measurements is developed and deployed on C-2 device to measure the radial
      profile of neutral density. Simultaneous measurements of electron density and
      temperature are done using CO(2) interferometer, Thomson scattering, and triple
      probes diagnostics along with absolute D-alpha radiation. Abel inversion was
      performed to get the time dependent radial profile of the local D-alpha emission
      density. Neutral density profiles are obtained under different machine conditions
      of titanium deposition.

PMID- 23126873
TI  - Density fluctuation measurements using beam emission spectroscopy on Heliotron J.
AB  - This paper describes the measurement of the density fluctuation using beam
      emission spectroscopy in Heliotron J, having the non-symmetrical helical-magnetic
      axis configuration. In order to optimize the sightlines, the numerical
      calculations are carried out to estimate the spatial resolution and the
      observation location. When a tangential neutral beam is used as diagnostic one,
      suitable sightlines from the newly installed diagnostic port are selected whose
      spatial resolution Deltarho is less than +/- 0.07 over the entire plasma region.
      Modification of the interference filter and the detection systems enables us to
      measure the radial profile of the density fluctuation. Each of the three coherent
      modes due to the fast-ion-driven magnetohydrodynamic instabilities has different
      radial structure of the density fluctuation.

PMID- 23126874
TI  - Spectral emission measurements of lithium on the lithium tokamak experiment.
AB  - There has been a long-standing collaboration between ORNL and PPPL on edge and
      boundary layer physics. As part of this collaboration, ORNL has a large role in
      the instrumentation and interpretation of edge physics in the lithium tokamak
      experiment (LTX). In particular, a charge exchange recombination spectroscopy
      (CHERS) diagnostic is being designed and undergoing staged testing on LTX. Here
      we present results of passively measured lithium emission at 5166.89 A in LTX in
      anticipation of active spectroscopy measurements, which will be enabled by the
      installation of a neutral beam in 2013. Preliminary measurements are made in
      transient LTX plasmas with plasma current, I(p) < 70 kA, ohmic heating power,
      P(oh) ~ 0.3 MW and discharge lifetimes of 10-15 ms. Measurements are made with a
      short focal length spectrometer and optics similar to the CHERS diagnostics on
      NSTX [R. E. Bell, Rev. Sci. Instrum. 68(2), 1273-1280 (1997)]. These preliminary
      measurements suggest that even without the neutral beam for active spectroscopy,
      there is sufficient passive lithium emission to allow for line-of-sight profile
      measurements of ion temperature, T(i); toroidal velocity and v(t). Results show
      peak T(i) = 70 eV and peak v(t) = 45 km/s were reached 10 ms into the discharge.

PMID- 23126875
TI  - A two photon absorption laser induced fluorescence diagnostic for fusion plasmas.
AB  - The quality of plasma produced in a magnetic confinement fusion device is
      influenced to a large extent by the neutral gas surrounding the plasma. The
      plasma is fueled by the ionization of neutrals, and charge exchange interactions
      between edge neutrals and plasma ions are a sink of energy and momentum. Here we
      describe a diagnostic capable of measuring the spatial distribution of neutral
      gas in a magnetically confined fusion plasma. A high intensity (5 MW/cm(2)),
      narrow bandwidth (0.1 cm(-1)) laser is injected into a hydrogen plasma to excite
      the Lyman beta transition via the simultaneous absorption of two 205 nm photons.
      The absorption rate, determined by measurement of subsequent Balmer alpha
      emission, is proportional to the number of particles with a given velocity.
      Calibration is performed in situ by filling the chamber to a known pressure of
      neutral krypton and exciting a transition close in wavelength to that used in
      hydrogen. We present details of the calibration procedure, including a technique
      for identifying saturation broadening, measurements of the neutral density
      profile in a hydrogen helicon plasma, and discuss the application of the
      diagnostic to plasmas in the DIII-D tokamak.

PMID- 23126876
TI  - A new neutral particle analyzer diagnostic and its first commissioning on HL-2A.
AB  - A new neutral particle analyzer diagnostic has been developed for HuanLiuqi-2A
      (commonly referred to as HL-2A), which can provide the neutral particle flux
      measurement along 11 separate sightlines, simultaneously, within a wider energy
      range (1-70 keV). It is an electrostatic type analyzer with a removable pinhole
      and special-shape condenser. The energy analysis can be flexibly achieved by
      controlling a preset stepwise high voltage on the condenser. It is compact and
      its field of view covers HL-2A cross section from -33 cm to 33 cm without "cross
      talk." The energy spectra and ion temperature profile have been obtained during
      its commissioning.

PMID- 23126877
TI  - Materials analysis and particle probe: a compact diagnostic system for in situ
      analysis of plasma-facing components (invited).
AB  - The objective of the materials analysis particle probe (MAPP) in NSTX is to
      enable prompt and direct analysis of plasma-facing components exposed to plasma
      discharges. MAPP allows multiple samples to be introduced to the level of the
      plasma-facing surface without breaking vacuum and analyzed using X-ray
      photoelectron spectroscopy (XPS), ion-scattering and direct recoil spectroscopy,
      and thermal desorption spectroscopy (TDS) immediately following the plasma
      discharge. MAPP is designed to operate as a diagnostic within the ~12 min NSTX
      minimum between-shot time window to reveal fundamental plasma-surface
      interactions. Initial calibration demonstrates MAPP's XPS and TDS capabilities.

PMID- 23126878
TI  - Calibration of an advanced neutral particle analyzer for the Madison Symmetric
      Torus reversed-field pinch.
AB  - A new E?B neutral particle analyzer, which has recently been installed on Madison
      Symmetric Torus (MST) reversed-field pinch (RFP), has now been calibrated,
      allowing the measurement of the fast ion density and energy distribution. This
      diagnostic, dubbed the advanced neutral particle analyzer (ANPA), can
      simultaneously produce time resolved measurements of the efflux of both hydrogen
      and deuterium ions from the plasma over a 35 keV energy range with an energy
      resolution of 2-4 keV and a time resolution of 10 MUs. These capabilities are
      needed to measure both majority ion heating that occurs during magnetic
      reconnection events in MST and the behavior of the fast ions from the 1 MW
      hydrogen neutral beam injector on MST. Calibration of the ANPA was performed
      using a custom ion source that resides in the flight tube between the MST and the
      ANPA. In this work, the ANPA will be described, the calibration procedure and
      results will be discussed, and initial measurements of the time evolution of 25
      keV neutral beam injection-born fast ions will be presented.

PMID- 23126879
TI  - New detection system and signal processing for the tokamak ISTTOK heavy ion beam
      diagnostic.
AB  - The tokamak ISTTOK havy ion beam diagnostic (HIBD) operates with a multiple cell
      array detector (MCAD) that allows for the plasma density and the plasma density
      fluctuations measurements simultaneously at different sampling volumes across the
      plasma. To improve the capability of the plasma density fluctuations
      investigations, a new detection system and new signal conditioning amplifier have
      been designed and tested. The improvements in MCAD design are presented which
      allow for nearly complete suppression of the spurious plasma background signal by
      applying a biasing potential onto special electrodes incorporated into MCAD. The
      new low cost and small size transimpedance amplifiers are described with the
      parameters of 400 kHz, 10(7) V/A, 0.4 nA of RMS noise, adequate for the plasma
      density fluctuations measurements.

PMID- 23126880
TI  - Internal magnetic field measurement on C-2 field-reversed configuration plasmas.
AB  - A long-lived field-reversed configuration (FRC) plasma has been produced in the C
      2 device by dynamically colliding and merging two oppositely directed, highly
      supersonic compact toroids (CTs). The reversed-field structure of the translated
      CTs and final merged-FRC state have been directly verified by probing the
      internal magnetic field structure using a multi-channel magnetic probe array near
      the midplane of the C-2 confinement chamber. Each of the two translated CTs
      exhibits significant toroidal fields (B(t)) with opposite helicity, and a
      relatively large B(t) remains inside the separatrix after merging.

PMID- 23126881
TI  - Near midplane scintillator-based fast ion loss detector on DIII-D.
AB  - A new scintillator-based fast-ion loss detector (FILD) installed near the outer
      midplane of the plasma has been commissioned on DIII-D. This detector
      successfully measures coherent fast ion losses produced by fast-ion driven
      instabilities (<=500 kHz). Combined with the first FILD at ~45 degrees  below the
      outer midplane [R. K. Fisher, et al., Rev. Sci. Instrum. 81, 10D307 (2010)], the
      two-detector system measures poloidal variation of losses. The phase space
      sensitivity of the new detector (gyroradius r(L) ~ [1.5-8] cm and pitch angle
      alpha ~ [35 degrees -85 degrees ]) is calibrated using neutral beam first orbit
      loss measurements. Since fast ion losses are localized poloidally, having two
      FILDs at different poloidal locations allows for the study of losses over a wider
      range of plasma shapes and types of loss orbits.

PMID- 23126882
TI  - Comparison of azimuthal ion velocity profiles using Mach probes, time delay
      estimation, and laser induced fluorescence in a linear plasma device.
AB  - We compare measurements of radially sheared azimuthal plasma flow based on time
      delay estimation (TDE) between two spatially separated Langmuir probes, Mach
      probes and laser induced fluorescence (LIF). TDE measurements cannot distinguish
      between ion fluid velocities and phase velocities. TDE and Mach probes are
      perturbative, so we compare the results against LIF, a non-perturbative,
      spatially resolved diagnostic technique that provides direct measurements of the
      ion velocity distribution functions. The bulk ion flow is determined from the
      Doppler shift of the Argon absorption line at 668.6139 nm. We compare results
      from all the three diagnostics, at various magnetic fields, which acts as a
      control knob for development of drift wave turbulence. We find that while Mach
      probes and LIF give similar profiles, TDE measurements typically overestimate the
      velocities and are also sensitive to the drift wave modes being investigated.

PMID- 23126883
TI  - Magnetic diagnostic suite of the C-2 field-reversed configuration experiment
      confinement vessel.
AB  - Magnetic measurements are a fundamental part of determining the size and shape of
      field-reversed configuration (FRC) plasmas in the C-2 device. The magnetic probe
      suite consists of 44 in-vessel and ex-vessel probes constructed using various
      technologies: ultra-high vacuum compatible mineral-insulated cable, nested triple
      axis coils hand-wound on ceramic bobbins, and commercial chip inductors mounted
      on printed circuit boards. Together, these probes measure the three-dimensional
      excluded flux profile of the FRC, which approximates the shape of the separatrix
      between the confined plasma volume and the scrape-off layer. High accuracy is
      achieved by using the extensive probe measurements to compensate for non-ideal
      effects such as flux leakage through the vacuum vessel and bulk motion of the FRC
      towards the wall. A subset of the probes is also used as a set of Mirnov arrays
      that provide sensitive detection of perturbations and oscillations of the FRC.

PMID- 23126884
TI  - Embedded calibration system for the DIII-D Langmuir probe analog fiber optic
      links.
AB  - This paper describes a generally applicable technique for simultaneously
      measuring offset and gain of 64 analog fiber optic data links used for the DIII-D
      fixed Langmuir probes by embedding a reference voltage waveform in the optical
      transmitted signal before every tokamak shot. The calibrated data channels allow
      calibration of the power supply control fiber optic links as well. The array of
      fiber optic links and the embedded calibration system described here makes
      possible the use of superior modern data acquisition electronics in the control
      room.

PMID- 23126885
TI  - Heavy ion beam probe advances from the first installation of the diagnostic on an
      RFP (invited).
AB  - Heavy ion beam probes have been installed on a variety of toroidal devices, but
      the first and only application on a reversed field pinch is the diagnostic on the
      Madison Symmetric Torus. Simultaneous measurements of spatially localized
      equilibrium potential and fluctuations of density and potential, previously
      inaccessible in the core of the reversed field pinch (RFP), are now attainable.
      These measurements reflect the unique strength of the heavy ion beam probe (HIBP)
      diagnostic. They will help determine the characteristics and evolution of
      electrostatic fluctuations and their role in transport, and determine the
      relation of the interior electric field and flows. Many aspects of the RFP
      present original challenges to HIBP operation and inference of plasma quantities.
      The magnetic field contributes to a number of the issues: the comparable
      magnitudes of the toroidal and poloidal fields and edge reversal result in highly
      three-dimensional beam trajectories; partial generation of the magnetic field by
      plasma current cause it and hence the beam trajectories to vary with time; and
      temporal topology and amplitude changes are common. Associated complications
      include strong ultraviolet radiation and elevated particle losses that can alter
      functionality of the electrostatic systems and generate noise on the detectors.
      These complexities have necessitated the development of new operation and data
      analysis techniques: the implementation of primary and secondary beamlines,
      adoption of alternative beam steering methods, development of higher precision
      electrostatic system models, refinement of trajectory calculations and sample
      volume modeling, establishment of stray particle and noise reduction methods, and
      formulation of alternative data analysis techniques. These innovative methods and
      the knowledge gained with this system are likely to translate to future HIBP
      operation on large scale stellarators and tokamaks.

PMID- 23126886
TI  - Development of the ITER magnetic diagnostic set and specification.
AB  - ITER magnetic diagnostics are now in their detailed design and R&D phase. They
      have passed their conceptual design reviews and a working diagnostic
      specification has been prepared aimed at the ITER project requirements. This
      paper highlights specific design progress, in particular, for the in-vessel
      coils, steady state sensors, saddle loops and divertor sensors. Key changes in
      the measurement specifications, and a working concept of software and electronics
      are also outlined.

PMID- 23126887
TI  - A photodiode-based neutral particle bolometer for characterizing charge-exchanged
      fast-ion behavior.
AB  - A neutral particle bolometer (NPB) has been designed and implemented on Tri Alpha
      Energy's C-2 device in order to spatially and temporally resolve the charge
      exchange losses of fast-ion populations originating from neutral beam injection
      into field-reversed configuration plasmas. This instrument employs a silicon
      photodiode as the detection device with an integrated tungsten filter coating to
      reduce sensitivity to light radiation. Here we discuss the technical aspects and
      calibration of the NPB, and report typical NPB measurement results of wall
      recycling effects on fast-ion losses.

PMID- 23126888
TI  - Pinned, optically aligned diagnostic dock for use on the Z facility.
AB  - The pinned optically aligned diagnostic dock (PODD) is a multi-configuration
      diagnostic platform designed to measure x-ray emission on the Z facility. The
      PODD houses two plasma emission acquisition (PEA) systems, which are aligned with
      a set of precision machined pins. The PEA systems are modular, allowing a single
      diagnostic housing to support several different diagnostics. The PEA
      configurations fielded to date include both time-resolved and time-integrated, 1D
      spatially resolving, elliptical crystal spectrometers, and time-integrated, 1D
      spatially resolving, convex crystal spectrometers. Additional proposed
      configurations include time-resolved, monochromatic mirrored pinhole imagers and
      arrays of filtered x-ray diodes, diamond photo-conducting diode detectors, and
      bolometers. The versatility of the PODD system will allow the diagnostic
      configuration of the Z facility to be changed without significantly adding to the
      turn-around time of the machine. Additionally, the PODD has been designed to
      allow instrument setup to be completed entirely off-line, leaving only a refined
      alignment process to be performed just prior to a shot, which is a significant
      improvement over the instrument the PODD replaces. Example data collected with
      the PODD are presented.

PMID- 23126889
TI  - A probabilistic model for the identification of confinement regimes and edge
      localized mode behavior, with implications to scaling laws.
AB  - Pattern recognition is becoming an important tool in fusion data analysis.
      However, fusion diagnostic measurements are often affected by considerable
      statistical uncertainties, rendering the extraction of useful patterns a
      significant challenge. Therefore, we assume a probabilistic model for the data
      and perform pattern recognition in the space of probability distributions. We
      show the considerable advantage of our method for identifying confinement regimes
      and edge localized mode behavior, and we discuss the potential for scaling laws.

PMID- 23126890
TI  - Diagnostic options for radiative divertor feedback control on NSTX-U.
AB  - A radiative divertor technique is used in present tokamak experiments and planned
      for ITER to mitigate high heat loads on divertor plasma-facing components (PFCs)
      to prevent excessive material erosion and thermal damage. In NSTX, a large
      spherical tokamak with lithium-coated graphite PFCs and high divertor heat flux
      (q(peak) <= 15 MW/m(2)), radiative divertor experiments have demonstrated a
      significant reduction of divertor peak heat flux simultaneously with good core H
      mode confinement using pre-programmed D(2) or CD(4) gas injections. In this work
      diagnostic options for a new real-time feedback control system for active
      radiative divertor detachment control in NSTX-U, where steady-state peak divertor
      heat fluxes are projected to reach 20-30 MW/m(2), are discussed. Based on the
      NSTX divertor detachment measurements and analysis, the control diagnostic
      signals available for NSTX-U include divertor radiated power, neutral pressure,
      spectroscopic deuterium recombination signatures, infrared thermography of PFC
      surfaces, and thermoelectric scrape-off layer current. In addition, spectroscopic
      "security" monitoring of possible confinement or pedestal degradation is
      recommended. These signals would be implemented in a digital plasma control
      system to manage the divertor detachment process via an actuator (impurity gas
      seeding rate).

PMID- 23126891
TI  - Inversion technique to obtain local rotation velocity and ion temperature from
      line-integrated measurements for elongated tokamak plasma.
AB  - An inversion technique is presented to calculate local toroidal and poloidal
      rotation velocity and ion temperature from line-integrated measurements of
      impurity lines by a matrix method. The effects of the rotation velocity on the
      ion temperature are analyzed in particular. An accurate inversion formula for the
      ion temperature is obtained. Several experimental geometries or configurations of
      line-integrated diagnostics in tokamaks are presented. For a plasma that is up
      down symmetric, both the toroidal rotation velocity and poloidal rotation
      velocity can be deduced from one special line-integrated measurement.

PMID- 23126892
TI  - High bandwidth differential amplifier for shock experiments.
AB  - We developed a high bandwidth differential amplifier for gas gun shock
      experiments of low-resistance metals. The circuit has a bandwidth up to 1 GHz,
      and is capable of measuring signals of <=1.5 V with a common mode rejection of
      250 V. Conductivity measurements of gas gun targets are measured by flowing high
      currents through the targets. The voltage is measured across the target using a
      technique similar to a four-point probe. Because of the design of the current
      source and load, the target voltage is ~250 V relative to ground. Since the
      expected voltage change in the target is <1 V, the differential amplifier must
      have a large common mode rejection. Various amplifying designs are shown,
      although the increased amplification decreases bandwidth. Bench tests show that
      the amplifier can withstand significant common mode dc voltage and measure 10 ns,
      and 50 mV signals.

PMID- 23126893
TI  - Mach-Zehnder recording systems for pulsed power diagnostics.
AB  - Fiber-optic  transmission  and recording  systems, based on Mach-Zehnder
      modulators, have been developed and installed at the National Ignition Facility
      (NIF), and are being developed for other pulsed-power facilities such as the Z
      accelerator at Sandia, with different requirements. We present the design and
      performance characteristics for the mature analog links, based on the system
      developed for the Gamma Reaction History diagnostic at the OMEGA laser and at
      NIF. For a single detector channel, two Mach-Zehnders are used to provide high
      dynamic range at the full recording bandwidth with no gaps in the coverage. We
      present laboratory and shot data to estimate upper limits on the radiation
      effects as they impact recorded data quality. Finally, we will assess the
      technology readiness level for mature and developing implementations of Mach
      Zehnder links for these environments.

PMID- 23126894
TI  - Modulated active charge exchange fast ion diagnostic for the C-2 field-reversed
      configuration experiment.
AB  - A diagnostic technique for measuring the fast-ion energy distribution in a field
      reversed configuration plasma was developed and tested on the C-2 experiment. A
      deuterium neutral beam modulated at 22 kHz is injected into the plasma, producing
      a localized charge-exchange target for the confined fast protons. The escaping
      fast neutrals are detected by a neutral particle analyzer. The target beam
      transverse size (~15 cm) defines the spatial resolution of the method. The
      equivalent current density of the target beam is <=0.15 A/cm(2), which
      corresponds to a neutral density (~6 * 10(9) cm(-3)) that highly exceeds the
      background neutral density in the core of C-2. The deuterium fast-ions due to the
      target beam (E ~27 keV), are not confined in C-2 and thus make a negligible
      contribution to the measured signals.

PMID- 23126895
TI  - Design of a dual sensor probe array for internal field measurement in Versatile
      Experiment Spherical Torus.
AB  - A dual sensor probe array is designed and constructed for internal magnetic field
      measurement at Versatile Experiment Spherical Torus (VEST) at the Seoul National
      University. Simultaneous use of Hall sensors and chip inductors allows cross
      calibration among the measurements and compensation for each other's weaknesses
      while their small sizes are expected to cause only mild plasma perturbations.
      Calibration of the dual sensor probe array, using a Helmholtz coil, shows good
      sensitivity for the magnetic field measurement of the VEST. Prior to Ohmic start
      up, the magnetic field structure inside the vacuum chamber is measured by using
      the calibrated probe array. The dual sensor probe array is expected to be useful
      in analyzing the temporal magnetic field structure change during the magnetic
      reconnection and in reconstruction of the current profile during the discharge of
      the VEST device.

PMID- 23126896
TI  - HELIOS: a helium line-ratio spectral-monitoring diagnostic used to generate high
      resolution profiles near the ion cyclotron resonant heating antenna on TEXTOR.
AB  - Radial profiles of electron temperature and density are measured at high spatial
      (~1 mm) and temporal (>=10 MUs) resolution using a thermal supersonic helium jet.
      A highly accurate detection system is applied to well-developed collisional
      radiative model codes to produce the profiles. Agreement between this measurement
      and an edge Thomson scattering measurement is found to be within the error bars
      (?20%). The diagnostic is being used to give profiles near the ion cyclotron
      resonant heating antenna on TEXTOR to better understand RF coupling to the core.

PMID- 23126897
TI  - Swinging reciprocating Mach probes for the high field side scrape-off layer in
      DIII-D.
AB  - A new pair of in situ reciprocating Mach probes termed swing probes has been
      deployed on the DIII-D centerpost for the 2012 experimental campaign. When not
      deployed, the entire assembly is housed in a <5 cm space underneath the
      centerpost tiles. This design is unique in that the probe swings vertically
      through the edge plasma, taking measurements along a 180 degrees  arc with a 20
      cm radius. The motion is powered by actuator coils that interact with the
      tokamak's magnetic field. Two electrodes maintain a Mach-pair orientation
      throughout the swing and provide measurements of saturation current, electron
      temperature, and parallel flow speeds up to the separatrix.

PMID- 23126898
TI  - Reliability issues for a bolometer detector for ITER at high operating
      temperatures.
AB  - The first detector prototypes for the ITER bolometer diagnostic featuring a 12.5
      MUm thick Pt-absorber have been realized and characterized in laboratory tests.
      The results show linear dependencies of the calibration parameters and are in
      line with measurements of prototypes with thinner absorbers. However, thermal
      cycling tests up to 450  degrees C of the prototypes with thick absorbers
      demonstrated that their reliability at these elevated operating temperatures is
      not yet sufficient. Profilometer measurements showed a deflection of the membrane
      hinting to stresses due to the deposition processes of the absorber. Finite
      element analysis (FEA) managed to reproduce the deflection and identified the
      highest stresses in the membrane in the region around the corners of the
      absorber. FEA was further used to identify changes in the geometry of the
      absorber with a positive impact on the intrinsic stresses of the membrane.
      However, further improvements are still necessary.

PMID- 23126899
TI  - A Langmuir probe diagnostic for time-of-flight measurements of transient plasmas
      produced by high-energy laser ablation.
AB  - We discuss here the development of a Langmuir probe (LP) diagnostic to examine
      high-density, high-temperature inhomogeneous plasmas such as those that can be
      created at the University of Rochester's Laboratory for Laser Energetics OMEGA
      facility. We have configured our diagnostic to examine the velocity of the plasma
      expanding from the target. We observe velocities of approximately 16-17 cm/MUs,
      with individual LP currents displaying complex structures, perhaps due to the
      multiple atomic species and ionization states that exist.

PMID- 23126900
TI  - A single-shot, multiwavelength electro-optic data-acquisition system for inertial
      confinement fusion applications (invited).
AB  - Electro-optic data-acquisition systems encode the output from voltage-history
      diagnostics onto optical signals. The optical signals can propagate long
      distances over fiber-optic links without degrading the bandwidth of the encoded
      signal while protecting the recording electronics from overvoltage damage. The
      sinusoidal response and tolerance to high-input voltages of the Mach-Zehnder
      modulator used for the encoding leads to the additional advantage of a high
      dynamic range and a reduced need for manually swapping attenuators. We have
      demonstrated a single-shot, electro-optic data-acquisition system with a 600:1
      dynamic range. This system provides optical isolation and a bandwidth of 6 GHz.
      The prototype system uses multiple optical wavelengths to allow for the
      multiplexing of up to eight signals onto one photodetector.

PMID- 23126901
TI  - Assessment and mitigation of diagnostic-generated electromagnetic interference at
      the National Ignition Facility.
AB  - Electromagnetic interference (EMI) is an ever-present challenge at laser
      facilities such as the National Ignition Facility (NIF). The major source of EMI
      at such facilities is laser-target interaction that can generate intense
      electromagnetic fields within, and outside of, the laser target chamber. In
      addition, the diagnostics themselves can be a source of EMI, even interfering
      with themselves. In this paper we describe EMI generated by ARIANE and DIXI,
      present measurements, and discuss effects of the diagnostic-generated EMI on
      ARIANE's CCD and on a PMT nearby DIXI. Finally we present some of the efforts we
      have made to mitigate the effects of diagnostic-generated EMI on NIF diagnostics.

PMID- 23126902
TI  - Diagnostics development for quasi-steady-state operation of the Wendelstein 7-X
      stellarator (invited).
AB  - The critical issues in the development of diagnostics, which need to work robust
      and reliable under quasi-steady state conditions for the discharge durations of
      30 min and which cannot be maintained throughout the one week duration of each
      operation phase of the Wendelstein 7-X stellarator, are being discussed.

PMID- 23126903
TI  - Suppression of spurious mode oscillation in mega-watt 77-GHz gyrotron as a high
      quality probe beam source for the collective Thomson scattering in LHD.
AB  - Collective Thomson scattering (CTS) diagnostic requires a strong probing beam to
      diagnose a bulk and fast ion distribution function in fusion plasmas. A mega-watt
      gyrotron for electron cyclotron resonance heating is used as a probing beam in
      the large helical device. Spurious mode oscillations are often observed during
      the turning on/off phase of the modulation. The frequency spectra of the 77-GHz
      gyrotron output power have been measured, and then one of the spurious modes,
      which interferes with the CTS receiver system, is identified as the TE(17,6) mode
      at the frequency of 74.7 GHz. The mode competition calculation indicates that the
      increase of the magnetic field strength at the gyrotron resonator can avoid such
      a spurious mode and excite only the main TE(18,6) mode. The spurious radiation at
      the 74.7 GHz is experimentally demonstrated to be suppressed in the stronger
      magnetic field than that optimized for the high-power operation.

PMID- 23126904
TI  - ORION laser target diagnostics.
AB  - The ORION laser facility is one of the UK's premier laser facilities which became
      operational at AWE in 2010. Its primary mission is one of stockpile stewardship,
      ORION will extend the UK's experimental plasma physics capability to the high
      temperature, high density regime relevant to Atomic Weapons Establishment's (AWE)
      program. The ORION laser combines ten laser beams operating in the ns regime with
      two sub ps short pulse chirped pulse amplification beams. This gives the UK a
      unique combined long pulse/short pulse laser capability which is not only
      available to AWE personnel but also gives access to our international partners
      and visiting UK academia. The ORION laser facility is equipped with a
      comprehensive suite of some 45 diagnostics covering optical, particle, and x-ray
      diagnostics all able to image the laser target interaction point. This paper
      focuses on a small selection of these diagnostics.

PMID- 23126905
TI  - Charged-particle spectroscopy for diagnosing shock rhoR and strength in NIF
      implosions.
AB  - The compact Wedge Range Filter (WRF) proton spectrometer was developed for OMEGA
      and transferred to the National Ignition Facility (NIF) as a National Ignition
      Campaign diagnostic. The WRF measures the spectrum of protons from D-(3)He
      reactions in tuning-campaign implosions containing D and (3)He gas; in this work
      we report on the first proton spectroscopy measurement on the NIF using WRFs. The
      energy downshift of the 14.7-MeV proton is directly related to the total rhoR
      through the plasma stopping power. Additionally, the shock proton yield is
      measured, which is a metric of the final merged shock strength.

PMID- 23126906
TI  - A novel particle time of flight diagnostic for measurements of shock- and
      compression-bang times in D3He and DT implosions at the NIF.
AB  - The particle-time-of-flight (pTOF) diagnostic, fielded alongside a wedge range
      filter (WRF) proton spectrometer, will provide an absolute timing for the shock
      burn weighted rhoR measurements that will validate the modeling of implosion
      dynamics at the National Ignition Facility (NIF). In the first phase of the
      project, pTOF has recorded accurate bang times in cryogenic DT, DT exploding
      pusher, and D(3)He implosions using DD or DT neutrons with an accuracy better
      than +/-70 ps. In the second phase of the project, a deflecting magnet will be
      incorporated into the pTOF design for simultaneous measurements of shock- and
      compression-bang times in D(3)He-filled surrogate implosions using D(3)He protons
      and DD-neutrons, respectively.

PMID- 23126907
TI  - Calibration techniques for fast-ion Dalpha diagnostics.
AB  - Fast-ion D(alpha) measurements are an application of visible charge-exchange
      recombination (CER) spectroscopy that provide information about the energetic ion
      population. Like other CER diagnostics, the standard intensity calibration is
      obtained with an integrating sphere during a vacuum vessel opening. An
      alternative approach is to create plasmas where the fast-ion population is known,
      then calculate the expected signals with a synthetic diagnostic code. The two
      methods sometimes agree well but are discrepant in other cases. Different
      background subtraction techniques and simultaneous measurements of visible
      bremsstrahlung and of beam emission provide useful checks on the calibrations and
      calculations.

PMID- 23126908
TI  - Solid debris collection for radiochemical diagnostics at the National Ignition
      Facility.
AB  - Radiochemical analysis of post-ignition debris inside the National Ignition
      Facility (NIF) target chamber can help determine various diagnostic parameters
      associated with the implosion efficiency of the fusion capsule. This technique is
      limited by the ability to distinguish ablator material from other debris and by
      the collection efficiency of the capsule debris after implosion. Prior to
      designing an on-line collection system, the chemical nature and distribution of
      the debris inside the chamber must be determined. The focus of our current work
      has been on evaluating capture of activated Au hohlraum debris on passive foils
      (5 cm diameter, 50 cm from target center) post-shot. Preliminary data suggest
      that debris distribution is locally heterogeneous along the equatorial and polar
      line-of-sights.

PMID- 23126909
TI  - Multi-shot analysis of the gamma reaction history diagnostic.
AB  - The gamma reaction history diagnostic at the National Ignition Facility has the
      capability to determine a number of important performance metrics for cryogenic
      deuterium-tritium implosions: the fusion burn width, bang time and yield, as well
      as the areal density of the compressed ablator. Extracting those values from the
      measured gamma rays of an implosion, requires accounting for a gamma-ray
      background in addition to the impulse response function of the instrument. To
      address these complications, we have constructed a model of the gamma-ray signal,
      and are developing a simultaneous multi-shot fitting routine to constrain its
      parameter space.

PMID- 23126910
TI  - Characterization of single crystal chemical vapor deposition diamond detectors
      for neutron spectrometry.
AB  - Detectors made from artificial chemical vapor deposition single crystal diamond
      have shown great potential for fast neutron spectrometry. In this paper, we
      present the results of measurements made at the Physikalisch-Technische
      Bundesanstalt accelerator using neutron fields in the energy range from 7 MeV to
      16 MeV. This study presents the first results of the characterization of the
      detector in this energy range.

PMID- 23126911
TI  - Advances in compact proton spectrometers for inertial-confinement fusion and
      plasma nuclear science.
AB  - Compact wedge-range-filter proton spectrometers cover proton energies ~3-20 MeV.
      They have been used at the OMEGA laser facility for more than a decade for
      measuring spectra of primary D(3)He protons in D(3)He implosions, secondary
      D(3)He protons in DD implosions, and ablator protons in DT implosions; they are
      now being used also at the National Ignition Facility. The spectra are used to
      determine proton yields, shell areal density at shock-bang time and compression
      bang time, fuel areal density, and implosion symmetry. There have been changes in
      fabrication and in analysis algorithms, resulting in a wider energy range, better
      accuracy and precision, and better robustness for survivability with indirect
      drive inertial-confinement-fusion experiments.

PMID- 23126912
TI  - The photonuclear neutron and gamma-ray backgrounds in the fast ignition
      experiment.
AB  - In the fast-ignition scheme, very hard x-rays (hereinafter referred to as gamma
      rays) are generated by Bremsstrahlung radiation from fast electrons. Significant
      backgrounds were observed around the deuterium-deuterium fusion neutron signals
      in the experiment in 2010. In this paper the backgrounds were studied in detail,
      based on Monte Carlo simulations, and they were confirmed to be gamma-rays from
      the target, scattered gamma-rays from the experimental bay walls (gamma'-rays),
      and neutrons generated by (gamma, n) reactions in either the target vacuum
      chamber or the diagnostic instruments (gamma-n neutrons).

PMID- 23126913
TI  - Validation of neutron emission profiles in MAST with a collimated neutron
      monitor.
AB  - A neutron camera with liquid scintillator detectors is used in MAST to measure
      the neutron emissivity from D(d,n)(3)He reactions along collimated lines of
      sight. In this work, the measured recoil proton pulse height spectra generated in
      the detectors by the incident neutrons is modelled taking into account the energy
      spectrum of the generated neutrons, their spatial distribution and transport to
      the detectors as well as the detector's response function. The contribution of
      scattered neutrons to the pulse height spectrum is also modelled. Good agreement
      is found between the experimental data and the simulations. Examples are given
      showing the sensitivity of the recoil proton pulse height spectra to different
      observation angles with respect the neutral beam injection and the plasma
      rotation direction.

PMID- 23126914
TI  - Characterizing time decay of bibenzyl scintillator using time correlated single
      photon counting.
AB  - The time decay of several scintillation materials has been measured using the
      time correlated single photon counting method and a new organic crystal with a
      highly suppressed delayed light has been identified. Results comparing the light
      decay of the bibenzyl crystal with a xylene based detector, which is currently
      installed at National Ignition Facility will be presented.

PMID- 23126915
TI  - Measuring the absolute deuterium-tritium neutron yield using the magnetic recoil
      spectrometer at OMEGA and the NIF.
AB  - A magnetic recoil spectrometer (MRS) has been installed and extensively used on
      OMEGA and the National Ignition Facility (NIF) for measurements of the absolute
      neutron spectrum from inertial confinement fusion implosions. From the neutron
      spectrum measured with the MRS, many critical implosion parameters are determined
      including the primary DT neutron yield, the ion temperature, and the down
      scattered neutron yield. As the MRS detection efficiency is determined from first
      principles, the absolute DT neutron yield is obtained without cross-calibration
      to other techniques. The MRS primary DT neutron measurements at OMEGA and the NIF
      are shown to be in excellent agreement with previously established yield
      diagnostics on OMEGA, and with the newly commissioned nuclear activation
      diagnostics on the NIF.

PMID- 23126916
TI  - Progress in obtaining an absolute calibration of a total deuterium-tritium
      neutron yield diagnostic based on copper activation.
AB  - The 350-keV Cockroft-Walton accelerator at Sandia National laboratory's Ion Beam
      facility is being used to calibrate absolutely a total DT neutron yield
      diagnostic based on the (63)Cu(n,2n)(62)Cu(beta+) reaction. These investigations
      have led to first-order uncertainties approaching 5% or better. The experiments
      employ the associated-particle technique. Deuterons at 175 keV impinge a 2.6 MUm
      thick erbium tritide target producing 14.1 MeV neutrons from the T(d,n)(4)He
      reaction. The alpha particles emitted are measured at two angles relative to the
      beam direction and used to infer the neutron flux on a copper sample. The induced
      (62)Cu activity is then measured and related to the neutron flux. This method is
      known as the F-factor technique. Description of the associated-particle method,
      copper sample geometries employed, and the present estimates of the uncertainties
      to the F-factor obtained are given.

PMID- 23126917
TI  - Calibration of neutron-yield diagnostics in attenuating and scattering
      environments.
AB  - We have performed absolute calibrations of a fusion-neutron-yield copper
      activation diagnostic in environments that significantly attenuate and scatter
      neutrons. We have measured attenuation and scattering effects and have compared
      the measurements to Monte Carlo simulations using the Monte Carlo N-Particle
      code. We find that measurements and simulations are consistent within 10%.

PMID- 23126918
TI  - A novel method for modeling the neutron time of flight detector response in
      current mode to inertial confinement fusion experiments (invited).
AB  - A novel method for modeling the neutron time of flight (nTOF) detector response
      in current mode for inertial confinement fusion experiments has been applied to
      the on-axis nTOF detectors located in the basement of the Z-Facility. It will be
      shown that this method can identify sources of neutron scattering, and is useful
      for predicting detector responses in future experimental configurations, and for
      identifying potential sources of neutron scattering when experimental set-ups
      change. This method can also provide insight on how much broadening neutron
      scattering contributes to the primary signals, which is then subtracted from
      them. Detector time responses are deconvolved from the signals, allowing a
      transformation from dN/dt to dN/dE, extracting neutron spectra at each detector
      location; these spectra are proportional to the absolute yield.

PMID- 23126919
TI  - The Radiochemical Analysis of Gaseous Samples (RAGS) apparatus for nuclear
      diagnostics at the National Ignition Facility (invited).
AB  - The Radiochemical Analysis of Gaseous Samples (RAGS) diagnostic apparatus was
      recently installed at the National Ignition Facility (NIF). Following a NIF shot,
      RAGS is used to pump the gas load from the NIF chamber for purification and
      isolation of the noble gases. After collection, the activated gaseous species are
      counted via gamma spectroscopy for measurement of the capsule areal density and
      fuel-ablator mix. Collection efficiency was determined by injecting a known
      amount of (135)Xe into the NIF chamber, which was then collected with RAGS.
      Commissioning was performed with an exploding pusher capsule filled with
      isotopically enriched (124)Xe and (126)Xe added to the DT gas fill. Activated
      xenon species were recovered post-shot and counted via gamma spectroscopy.
      Results from the collection and commissioning tests are presented. The
      performance of RAGS allows us to establish a noble gas collection method for
      measurement of noble gas species produced via neutron and charged particle
      reactions in a NIF capsule.

PMID- 23126920
TI  - Copper activation deuterium-tritium neutron yield measurements at the National
      Ignition Facility.
AB  - A DT neutron yield diagnostic based on the reactions, (63)Cu(n,2n)(62)Cu(beta(+))
      and (65)Cu(n,2n)( 64) Cu(beta(+)), has been fielded at the National Ignition
      Facility (NIF). The induced copper activity is measured using a NaI gamma-gamma
      coincidence system. Uncertainties in the 14-MeV DT yield measurements are on the
      order of 7% to 8%. In addition to measuring yield, the ratio of activities
      induced in two, well-separated copper samples are used to measure the relative
      anisotropy of the fuel rhoR to uncertainties as low as 5%.

PMID- 23126921
TI  - High-resolution spectroscopy used to measure inertial confinement fusion neutron
      spectra on Omega (invited).
AB  - The areal density (rhoR) of cryogenic DT implosions on Omega is inferred by
      measuring the spectrum of neutrons that elastically scatter off the dense
      deuterium (D) and tritium (T) fuel. Neutron time-of-flight (nTOF) techniques are
      used to measure the energy spectrum with high resolution. High signal-to
      background data has been recorded on cryogenic DT implosions using a well
      collimated 13.4-m line of sight and an nTOF detector with an advanced liquid
      scintillator compound. An innovative method to analyze the elastically scattered
      neutron spectra was developed using well-known cross sections of the DT nuclear
      reactions. The estimated areal densities are consistent with alternative rhoR
      measurements and 1-D simulations.

PMID- 23126922
TI  - Perpendicular and tangential angularly resolved multi-sight neutral particle
      analyzer system in LHD.
AB  - The particle loss in a helical plasma can be found by measuring the angular
      distribution of the energetic neutral particles using the angularly resolved
      multi-sightline neutral particle analyzer (ARMS). In ARMS, the AXUV detector with
      20 segments usually used as UV monitor is utilized as the particle detector. Two
      ARMSs, which are installed with perpendicular and tangential views are operated
      for measuring the real time neutral particle distribution and investigating the
      particle loss.

PMID- 23126923
TI  - Extreme ultraviolet spectroscopy and modeling of Cu on the SSPX Spheromak and
      laser plasma "Sparky".
AB  - Impurities play a critical role in magnetic fusion research. In large quantities,
      impurities can cool and dilute plasma creating problems for achieving ignition
      and burn; however in smaller amounts the impurities could provide valuable
      information about several plasma parameters through the use of spectroscopy. Many
      impurity ions radiate within the extreme ultraviolet (EUV) range. Here, we report
      on spectra from the silver flat field spectrometer, which was implemented at the
      Sustained Spheromak Physics experiment (SSPX) to monitor ion impurity emissions.
      The chamber within the SSPX was made of Cu, which makes M-shell Cu a prominent
      impurity signature. The Spect3D spectral analysis code was utilized to identify
      spectral features in the range of 115-315 A and to more fully understand the
      plasma conditions. A second set of experiments was carried out on the compact
      laser-plasma x-ray/EUV facility "Sparky" at UNR, with Cu flat targets used. The
      EUV spectra were recorded between 40-300 A and compared with results from SSPX.

PMID- 23126924
TI  - C-III flow measurements with a coherence imaging spectrometer.
AB  - This work describes a coherence imaging spectrometer capable of making spatially
      resolved CIII flow measurements in the DIII-D lower divertor. The spectrometer
      exploits a periscope view of the plasma to produce line-of-sight averaged
      velocity measurements of CIII. From these chord averaged flow measurements, a 2D
      poloidal cross section of the CIII flow is tomographically reconstructed. Details
      of the diagnostic setup, acquired data, and data analysis will be presented,
      along with prospects for future applications.

PMID- 23126925
TI  - X-ray absorption spectroscopy of aluminum z-pinch plasma with tungsten
      backlighter planar wire array source.
AB  - Absorption features from K-shell aluminum z-pinch plasmas have recently been
      studied on Zebra, the 1.7 MA pulse power generator at the Nevada Terawatt
      Facility. In particular, tungsten plasma has been used as a semi-backlighter
      source in the generation of aluminum K-shell absorption spectra by placing a
      single Al wire at or near the end of a single planar W array. All spectroscopic
      experimental results were recorded using a time-integrated, spatially resolved
      convex potassium hydrogen phthalate (KAP) crystal spectrometer. Other diagnostics
      used to study these plasmas included x-ray detectors, optical imaging, laser
      shadowgraphy, and time-gated and time-integrated x-ray pinhole imagers. Through
      comparisons with previous publications, Al K-shell absorption lines are shown to
      be from much lower electron temperature (~10-40 eV) plasmas than emission spectra
      (~350-500 eV).

PMID- 23126926
TI  - Implementation of a multichannel soft x-ray diagnostic for electron temperature
      measurements in TJ-II high-density plasmas.
AB  - Based on the multi-foil technique, a multichannel soft x-ray diagnostic for
      electron temperature measurements has been recently implemented in the TJ-II
      stellarator. The diagnostic system is composed by four photodiodes arrays with
      beryllium filters of different thickness. An in-vacuum amplifier board is coupled
      to each array, aiming at preventing induced noise currents. The Thomson
      scattering and the vacuum ultraviolet survey diagnostics are used for assessing
      plasma profiles and composition, being the analysis carried out with the
      radiation code IONEQ. The electron temperature is determined through the
      different signal-pair ratios with temporal and spatial resolution. The design and
      preliminary results from the diagnostic are presented.

PMID- 23126927
TI  - X-ray bang-time measurements at the National Ignition Facility using a diamond
      detector.
AB  - A chemical vapor deposition polycrystalline photoconductive diamond detector was
      fielded at NIF to measure the time of peak x-ray emission, or x-ray bang time, of
      inertial confinement fusion implosions. Imaging the capsule with a pinhole
      provides contrast against Hohlraum emission, allowing clear identification of the
      capsule component in the raw scope trace. X-ray bang time was measured to within
      +/-41-46 ps with the internal photoconductive diamond detector.

PMID- 23126928
TI  - Ultra fast x-ray streak camera for ten inch manipulator based platforms.
AB  - Ultra fast x-ray streak cameras are a staple for time resolved x-ray
      measurements. There is a need for a ten inch manipulator (TIM) based streak
      camera that can be fielded in a newer large scale laser facility. The Lawrence
      Livermore National Laboratory ultra fast streak camera's drive electronics have
      been upgraded and redesigned to fit inside a TIM tube. The camera also has a new
      user interface that allows for remote control and data acquisition. The system
      has been outfitted with a new sensor package that gives the user more operational
      awareness and control.

PMID- 23126929
TI  - Streaked x-ray spectrometer having a discrete selection of Bragg geometries for
      Omega.
AB  - The streaked x-ray spectrometer (SXS) is used with streak cameras [D. H.
      Kalantar, P. M. Bell, R. L. Costa, B. A. Hammel, O. L. Landen, T. J. Orzechowski,
      J. D. Hares, and A. K. L. Dymoke-Bradshaw, in 22nd International Congress on High
      Speed Photography and Photonics, edited by D. L. Paisley and A. M. Frank (SPIE,
      Bellingham, WA, 1997), Vol. 2869, p. 680] positioned with a ten-inch manipulator
      on OMEGA [T. R. Boehly et al., Opt. Commun. 133, 495 (1997)] and OMEGA EP [L. J.
      Waxer et al., Presented at CLEO/QELS 2008, San Jose, CA, 4-9 May 2008 (Paper
      JThB1)] for time-resolved, x-ray spectroscopy of laser-produced plasmas in the
      1.4- to 20-keV photon-energy range. These experiments require measuring a portion
      of this photon-energy range to monitor a particular emission or absorption
      feature of interest. The SXS relies on a pinned mechanical reference system to
      create a discrete set of Bragg reflection geometries for a variety of crystals. A
      wide selection of spectral windows is achieved accurately and efficiently using
      this technique. It replaces the previous spectrometer designs that had a
      continuous Bragg angle adjustment and required a tedious alignment calibration
      procedure. The number of spectral windows needed for the SXS was determined by
      studying the spectral ranges selected by OMEGA users over the last decade. These
      selections are easily configured in the SXS using one of the 25 discrete Bragg
      reflection geometries and one of the six types of Bragg crystals, including two
      curved crystals.

PMID- 23126930
TI  - Imaging x-ray Thomson scattering spectrometer design and demonstration (invited).
AB  - In many laboratory astrophysics experiments, intense laser irradiation creates
      novel material conditions with large, one-dimensional gradients in the
      temperature, density, and ionization state. X-ray Thomson scattering is a
      powerful technique for measuring these plasma parameters. However, the scattered
      signal has previously been measured with little or no spatial resolution, which
      limits the ability to diagnose inhomogeneous plasmas. We report on the
      development of a new imaging x-ray Thomson spectrometer (IXTS) for the Omega
      laser facility. The diffraction of x-rays from a toroidally curved crystal
      creates high-resolution images that are spatially resolved along a one
      dimensional profile while spectrally dispersing the radiation. This focusing
      geometry allows for high brightness while localizing noise sources and improving
      the linearity of the dispersion. Preliminary results are presented from a
      scattering experiment that used the IXTS to measure the temperature profile of a
      shocked carbon foam.

PMID- 23126931
TI  - Compact "diode-based" multi-energy soft x-ray diagnostic for NSTX.
AB  - A novel and compact, diode-based, multi-energy soft x-ray (ME-SXR) diagnostic has
      been developed for the National Spherical Tokamak Experiment. The new edge ME-SXR
      system tested on NSTX consists of a set of vertically stacked diode arrays, each
      viewing the plasma tangentially through independent pinholes and filters
      providing an overlapping view of the plasma midplane which allows simultaneous
      SXR measurements with coarse sub-sampling of the x-ray spectrum. Using computed x
      ray spectral emission data, combinations of filters can provide fast (>10 kHz)
      measurements of changes in the electron temperature and density profiles
      providing a method to "fill-in" the gaps of the multi-point Thomson scattering
      system.

PMID- 23126932
TI  - ?10 eV ionization shift in Ir Kalpha2 from a near-coincident Lu K-edge.
AB  - Close to an x-ray filter's K-edge the transmission depends strongly on the photon
      energy. For a few atom pairs, the K-edge of one is only a few tens of eV higher
      than a K-line energy of another, so that a small change in the line's energy
      becomes a measurable change in intensity behind such a matching filter.
      Lutetium's K-edge is ?27 eV above iridium's Kalpha(2) line, ?63.287 keV for cold
      Ir. A Lu filter reduces this line's intensity by ?10 % when it is emitted by a
      plasma, indicating an ionization shift Deltaepsilon?10+/-1 eV.

PMID- 23126933
TI  - Rest-wavelength fiducials for the ITER core imaging x-ray spectrometer.
AB  - Absolute wavelength references are needed to derive the plasma velocities from
      the Doppler shift of a given line emitted by a moving plasma. We show that such
      reference standards exist for the strongest x-ray line in neonlike W(64+), which
      has become the line of choice for the ITER (Latin "the way") core imaging x-ray
      spectrometer. Close-by standards are the Hf Lbeta(3) line and the Ir Lalpha(2)
      line, which bracket the W(64+) line by +/-30 eV; other standards are given by the
      Ir Lalpha(1) and Lalpha(2) lines and the Hf Lbeta(1) and Lbeta(2) lines, which
      bracket the W(64+) line by +/-40 and +/-160 eV, respectively. The reference
      standards can be produced by an x-ray tube built into the ITER spectrometer. We
      present spectra of the reference lines obtained with an x-ray microcalorimeter
      and compare them to spectra of the W(64+) line obtained both with an x-ray
      microcalorimeter and a crystal spectrometer.

PMID- 23126934
TI  - Transmission crystal x-ray spectrometer covering the 6 keV-18 keV energy range
      with E/DeltaE = 1800 instrumental resolving power.
AB  - A high-resolution x-ray spectrometer utilizing a thin quartz transmission crystal
      and covering the 6 keV-18 keV energy range has been developed and tested. The
      spectrometer consists of a cylindrically bent crystal in a vacuum housing. The
      crystal position and the range of Bragg angles that are incident on the crystal
      can be adjusted to record an ~4 keV wide spectrum in the 6 keV-18 keV range. The
      spectrometer is of the Cauchois type and has a compact linear geometry that is
      convenient for deployment at laser-produced plasma, EBIT, and other x-ray
      sources. Test spectra of the W L and Mo K lines from laboratory sources have
      linewidths as small as 11 eV, approaching the natural widths, and instrumental
      resolving power as high as 1800. Techniques for enhancing the energy resolution
      are experimentally demonstrated.

PMID- 23126935
TI  - Measuring electron-positron annihilation radiation from laser plasma
      interactions.
AB  - We investigated various diagnostic techniques to measure the 511 keV annihilation
      radiations. These include step-wedge filters, transmission crystal spectroscopy,
      single-hit CCD detectors, and streaked scintillating detection. While none of the
      diagnostics recorded conclusive results, the step-wedge filter that is sensitive
      to the energy range between 100 keV and 700 keV shows a signal around 500 keV
      that is clearly departing from a pure Bremsstrahlung spectrum and that we ascribe
      to annihilation radiation.

PMID- 23126936
TI  - Spectral analysis of x-ray emission created by intense laser irradiation of
      copper materials.
AB  - We have measured the x-ray emission, primarily from K(alpha),K(beta), and
      He(alpha) lines, of elemental copper foil and "foam" targets irradiated with a
      mid-10(16) W/cm(2) laser pulse. The copper foam at 0.1 times solid density is
      observed to produce 50% greater He(alpha) line emission than copper foil, and the
      measured signal is well-fit by a sum of three synthetic spectra generated by the
      atomic physics code FLYCHK. Additionally, spectra from both targets reveal
      characteristic inner shell K(alpha) transitions from hot electron interaction
      with the bulk copper. However, only the larger-volume foam target produced
      significant K(beta) radiation, confirming a lower bulk temperature in the higher
      volume sample.

PMID- 23126937
TI  - Imaging of high-energy x-ray emission from cryogenic thermonuclear fuel
      implosions on the NIF.
AB  - Accurately assessing and optimizing the implosion performance of inertial
      confinement fusion capsules is a crucial step to achieving ignition on the NIF.
      We have applied differential filtering (matched Ross filter pairs) to provide
      broadband time-integrated absolute x-ray self-emission images of the imploded
      core of cryogenic layered implosions. This diagnostic measures the temperature-
      and density-sensitive bremsstrahlung emission and provides estimates of hot spot
      mass, mix mass, and pressure.

PMID- 23126938
TI  - Dilation x-ray imager a new/faster gated x-ray imager for the NIF.
AB  - As the yield on implosion shots increases it is expected that the peak x-ray
      emission reduces to a duration with a FWHM as short as 20 ps for ~7 * 10(18)
      neutron yield. However, the temporal resolution of currently used gated x-ray
      imagers on the NIF is 40-100 ps. We discuss the benefits of the higher temporal
      resolution for the NIF and present performance measurements for dilation x-ray
      imager, which utilizes pulse-dilation technology [T. J. Hilsabeck et al., Rev.
      Sci. Instrum. 81, 10E317 (2010)] to achieve x-ray imaging with temporal gate
      times below 10 ps. The measurements were conducted using the COMET laser, which
      is part of the Jupiter Laser Facility at the Lawrence Livermore National
      Laboratory.

PMID- 23126939
TI  - Source geometric considerations for OMEGA Dante measurements.
AB  - The Dante is a 15 channel filtered diode array which is installed on the OMEGA
      laser facility at the Laboratory for Laser Energetics, University of Rochester.
      The system yields the spectrally and temporally resolved radiation flux from 50
      eV to 10 keV from various targets (i.e., Hohlraum, gas pipes, etc.). The absolute
      flux is determined from the radiometric calibration of the x-ray diodes, filters,
      and mirrors and an unfold algorithm applied to the recorded voltages from each
      channel. The unfold algorithm assumes an emitting source that is spatially
      uniform and has a constant area as a function of photon energy. The emitting x
      ray source is usually considered to be the laser entrance hole (LEH) of a given
      diameter for Hohlraum type targets or the effective wall area of high conversion
      efficiency K-shell type targets. This assumption can be problematic for several
      reasons. High intensity regions or "hot spots" in the x-ray are observed where
      the drive laser beams strike the target. The "hot spots" create non-uniform
      emission seen by the Dante. Additionally, thinned walled (50 MUm) low-Z targets
      (C(22)H(10)N(2)O(5)) have an energy dependent source size since the target's
      walls will be fully opaque for low energies (E < 2-3 keV) yet fully transmissive
      at higher energies. Determining accurate yields can be challenging for these
      types of targets. Discussion and some analysis will be presented.

PMID- 23126940
TI  - Methods for characterizing x-ray detectors for use at the National Ignition
      Facility.
AB  - Gated and streaked x-ray detectors generally require corrections in order to
      counteract instrumental effects in the data. The method of correcting for gain
      variations in gated cameras fielded at National Ignition Facility (NIF) is
      described. Four techniques for characterizing the gated x-ray detectors are
      described. The current principal method of characterizing x-ray instruments is
      the production of controlled x-ray emission by laser-generated plasmas as a
      dedicated shot at the NIF. A recently commissioned pulsed x-ray source has the
      potential to replace the other characterization systems. This x-ray source
      features a pulsed power source consisting of a Marx generator, capacitor bank
      that is charged in series and discharged in parallel, producing up to 300 kV. The
      pulsed x-ray source initially suffered from a large jitter (~60 ns), but the
      recent addition of a pulsed laser to trigger the spark gap has reduced the jitter
      to ~5 ns. Initial results show that this tool is a promising alternative to the
      other flat fielding techniques.

PMID- 23126941
TI  - South pole bang-time diagnostic on the National Ignition Facility (invited).
AB  - The south pole bang-time diagnostic views National Ignition Facility (NIF)
      implosions through the lower Hohlraum laser entrance hole to measure the time of
      peak x-ray emission (peak compression) in indirect-drive implosions. Five
      chemical-vapor-deposition diamond photoconductive detectors with different
      filtrations and sensitivities record the time-varying x rays emitted by the
      target. Wavelength selecting highly oriented pyrolytic graphite crystal mirror
      monochromators increase the x-ray signal-to-background ratio by filtering for 11
      keV emission. Diagnostic timing and the in situ temporal instrument response
      function are determined from laser impulse shots on the NIF. After signal
      deconvolution and background removal, the bang time is determined to 45-ps
      accuracy. The x-ray "yield" (mJ/sr/keV at 11 keV) is determined from the time
      integral of the corrected peak signal.

PMID- 23126942
TI  - Absolute determination of charge-coupled device quantum detection efficiency
      using Si K-edge x-ray absorption fine structure.
AB  - We report a method to determine the quantum detection efficiency and the
      absorbing layers on a front-illuminated charge-coupled device (CCD). The CCD
      under study, as part of a crystal spectrometer, measures intense continuum x-ray
      emission from a picosecond laser-produced plasma and spectrally resolves the Si K
      edge x-ray absorption fine structure due to the electrode structure of the
      device. The CCD response across the Si K-edge shows a large discontinuity as well
      as a number of oscillations that are identified individually and uniquely from
      Si, SiO(2), and Si(3)N(4) layers. From the spectral analysis of the structure and
      K-edge discontinuity, the active layer thickness and the different absorbing
      layers thickness can be determined precisely. A precise CCD detection model from
      0.2 to 10 keV can be deduced from this highly sensitive technique.

PMID- 23126943
TI  - Measurement of electron temperature of imploded capsules at the National Ignition
      Facility.
AB  - The electron and ion temperatures of the imploded core plasma are two of the most
      important metrics of inertial confinement fusion experiments. We have developed a
      technique for inferring electron temperatures from the contrast of x-ray images
      observed through a group of x-ray filters. Generally, the plasma electron
      temperature exhibits spatial and temporal variations, so time-averaged and time
      resolved measurements are expected to yield somewhat different results. By
      analyzing the intensity of images observed with both a time-integrated detector
      (imaging plates) and a time-resolved detector (gated micro-channel plate), we
      found the electron temperature observed from x-ray images to be systematically
      higher than the ion temperature inferred from fusion neutron spectroscopy.

PMID- 23126944
TI  - Integrated x-ray reflectivity measurements of elliptically curved pentaerythritol
      crystals.
AB  - The elliptically curved pentaerythritol (PET) crystals used in the Supersnout 2 x
      ray spectrometer on the National Ignition Facility at Lawrence Livermore National
      Laboratory have been calibrated photometrically in the range of 5.5-16 keV. The
      elliptical geometry provides broad spectral coverage and minimizes the
      degradation of spectral resolution due to the finite source size. The
      reflectivity curve of the crystals was measured using a x-ray line source. The
      integrated reflectivity (R(I)) and width of its curve (DeltaTheta) were the
      measurements of major interest. The former gives the spectrometer throughput, and
      the latter gives the spectrometer resolving power. Both parameters are found to
      vary considerably with the radius of curvature of the crystal and with spectral
      energy. The results are attributed to an enhanced mosaic effect due to the
      increase in curvature. There are also contributions from the crystal cleaving and
      gluing processes.

PMID- 23126945
TI  - X-ray streak camera cathode development and timing accuracy of the 4omega
      ultraviolet fiducial system at the National Ignition Facility.
AB  - The convergent ablator experiments at the National Ignition Facility (NIF) are
      designed to measure the peak velocity and remaining ablator mass of an indirectly
      driven imploding capsule. Such a measurement can be performed using an x-ray
      source to backlight the capsule and an x-ray streak camera to record the capsule
      as it implodes. The ultimate goal of this experiment is to achieve an accuracy of
      2% in the velocity measurement, which translates to a +/-2 ps temporal accuracy
      over any 300 ps interval for the streak camera. In order to achieve this, a
      4omega (263 nm) temporal fiducial system has been implemented for the x-ray
      streak camera at NIF. Aluminum, titanium, gold, and silver photocathode materials
      have been tested. Aluminum showed the highest relative quantum efficiency, with
      five times more peak signal counts per fiducial pulse when compared to Gold. The
      fiducial pulse data were analyzed to determine the centroiding statistical
      accuracy for incident laser pulse energies of 1 and 10 nJ, showing an accuracy of
      +/-1.6 ps and +/-0.7 ps, respectively.

PMID- 23126946
TI  - Application of spatially resolved high resolution crystal spectrometry to
      inertial confinement fusion plasmas.
AB  - High resolution (lambda/Deltalambda ~ 10 000) 1D imaging x-ray spectroscopy using
      a spherically bent crystal and a 2D hybrid pixel array detector is used world
      wide for Doppler measurements of ion-temperature and plasma flow-velocity
      profiles in magnetic confinement fusion plasmas. Meter sized plasmas are
      diagnosed with cm spatial resolution and 10 ms time resolution. This concept can
      also be used as a diagnostic of small sources, such as inertial confinement
      fusion plasmas and targets on x-ray light source beam lines, with spatial
      resolution of micrometers, as demonstrated by laboratory experiments using a 250
      MUm (55)Fe source, and by ray-tracing calculations. Throughput calculations agree
      with measurements, and predict detector counts in the range 10(-8)-10(-6) times
      source x-rays, depending on crystal reflectivity and spectrometer geometry.
      Results of the lab demonstrations, application of the technique to the National
      Ignition Facility (NIF), and predictions of performance on NIF will be presented.

PMID- 23126947
TI  - Bragg x-ray survey spectrometer for ITER.
AB  - Several potential impurity ions in the ITER plasmas will lead to loss of confined
      energy through line and continuum emission. For real time monitoring of
      impurities, a seven channel Bragg x-ray spectrometer (XRCS survey) is considered.
      This paper presents design and analysis of the spectrometer, including x-ray
      tracing by the Shadow-XOP code, sensitivity calculations for reference H-mode
      plasma and neutronics assessment. The XRCS survey performance analysis shows that
      the ITER measurement requirements of impurity monitoring in 10 ms integration
      time at the minimum levels for low-Z to high-Z impurity ions can largely be met.

PMID- 23126948
TI  - High-resolution spectroscopy for Doppler-broadening ion temperature measurements
      of implosions at the National Ignition Facility.
AB  - Future implosion experiments at the national ignition facility (NIF) will
      endeavor to simultaneously measure electron and ion temperatures with temporal
      and spatial resolution in order to explore non-equilibrium temperature
      distributions and their relaxation toward equilibrium. In anticipation of these
      experiments, and with understanding of the constraints of the NIF facility
      environment, we have explored the use of Doppler broadening of mid-Z dopant
      emission lines, such as krypton He-alpha at 13 keV, as a diagnostic of time- and
      potentially space-resolved ion temperature. We have investigated a number of
      options analytically and with numerical raytracing, and we have identified
      several promising candidate spectrometer designs that meet the expected
      requirements of spectral and temporal resolution and data signal-to-noise ratio
      for gas-filled exploding pusher implosions, while providing maximum flexibility
      for use on a variety of experiments that potentially include burning plasma.

PMID- 23126949
TI  - Investigation of iron opacity experiment plasma gradients with synthetic data
      analyses.
AB  - Experiments have been performed at Sandia National Laboratories Z-facility to
      validate iron opacity models relevant to the solar convection/radiation zone
      boundary. Sample conditions were measured by mixing Mg with the Fe and using Mg K
      shell line transmission spectra, assuming that the plasma was uniform. We develop
      a spectral model that accounts for hypothetical gradients, and compute synthetic
      spectra to quantitatively evaluate the plasma gradient size that can be
      diagnosed. Two sample designs are investigated, assuming linear temperature and
      density gradients. First, Mg uniformly mixed with Fe enables temperature
      gradients greater than 10% to be detected. The second design uses Mg mixed into
      one side and Al mixed into the other side of the sample in an attempt to more
      accurately infer the sample gradient. Both temperature and density gradients as
      small as a few percent can be detected with this design. Experiments have
      successfully recorded spectra with the second design. In future research, the
      spectral model will be used to place bounds on gradients that exist in Z opacity
      experiments.

PMID- 23126950
TI  - High-performance double-filter soft x-ray diagnostic for measurement of electron
      temperature structure and dynamics.
AB  - A new soft x-ray (SXR) T(e) and tomography diagnostic has been developed for MST
      that can be used for simultaneous SXR spectrum measurement, tomographically
      reconstructed emissivity, and reconstructed and line-of-sight electron
      temperature. The diagnostic utilizes high-performance differential transimpedance
      amplifiers (gain 10(5)-10(9)) to provide fast time response (up to 125 kHz),
      allowing for the study of plasma structure dynamics. SXR double-foil T(e)
      measurements are consistent with Thomson scattering. SXR brightness through a
      variety of filter thicknesses has been combined with charge exchange
      recombination spectroscopy (CHERS) impurity density measurements to determine the
      plasma energy spectrum. Magnetic pickup from the fluctuating magnetic fields in
      the plasma (B~20 gauss at 10-20 kHz) has been dramatically reduced by improving
      the detector and housing design, so that nanoampere diode currents are now
      measured without interference from the substantial fluctuating magnetic field
      incident on the plasma facing surface of the probe.

PMID- 23126951
TI  - Upgrades of the high resolution imaging x-ray crystal spectrometers on
      experimental advanced superconducting tokamak.
AB  - Two imaging x-ray crystal spectrometers, the so-called "poloidal" and
      "tangential" spectrometers, were recently implemented on experimental advanced
      superconducting tokamak (EAST) to provide spatially and temporally resolved
      impurity ion temperature (T(i)), electron temperature (T(e)) and rotation
      velocity profiles. They are derived from Doppler width of W line for Ti, the
      intensity ratio of Li-like satellites to W line for Te, and Doppler shift of W
      line for rotation. Each spectrometer originally consisted of a spherically curved
      crystal and a two-dimensional multi-wire proportional counter (MWPC) detector.
      Both spectrometers have now been upgraded. The layout of the tangential
      spectrometer was modified, since it had to be moved to a different port, and the
      spectrometer was equipped with two high count rate Pilatus detectors (Model 100
      K) to overcome the count rate limitation of the MWPC and to improve its time
      resolution. The poloidal spectrometer was equipped with two spherically bent
      crystals to record the spectra of He-like and H-like argon simultaneously and
      side by side on the original MWPC. These upgrades are described, and new results
      from the latest EAST experimental campaign are presented.

PMID- 23126952
TI  - A new compact, high sensitivity neutron imaging system.
AB  - We have developed a new small neutron imaging system (SNIS) diagnostic for the
      OMEGA laser facility. The SNIS uses a penumbral coded aperture and has been
      designed to record images from low yield (10(9)-10(10) neutrons) implosions such
      as those using deuterium as the fuel. This camera was tested at OMEGA in 2009 on
      a rugby hohlraum energetics experiment where it recorded an image at a yield of
      1.4 * 10(10). The resolution of this image was 54 MUm and the camera was located
      only 4 meters from target chamber centre. We recently improved the instrument by
      adding a cooled CCD camera. The sensitivity of the new camera has been fully
      characterized using a linear accelerator and a (60)Co gamma-ray source. The
      calibration showed that the signal-to-noise ratio could be improved by using raw
      binning detection.

PMID- 23126953
TI  - A soft x-ray transmission grating imaging-spectrometer for the National Ignition
      Facility.
AB  - A soft x-ray transmission grating spectrometer has been designed for use on high
      energy-density physics experiments at the National Ignition Facility (NIF);
      coupled to one of the NIF gated x-ray detectors it records 16 time-gated spectra
      between 250 and 1000 eV with 100 ps temporal resolution. The trade-off between
      spectral and spatial resolution leads to an optimized design for measurement of
      emission around the peak of a 100-300 eV blackbody spectrum. Performance
      qualification results from the NIF, the Trident Laser Facility and vacuum
      ultraviolet beamline at the National Synchrotron Light Source, evidence a <100
      MUm spatial resolution in combination with a source-size limited spectral
      resolution that is <10 eV at photon energies of 300 eV.

PMID- 23126954
TI  - A methodology for calibrating wavelength dependent spectral resolution for
      crystal spectrometers.
AB  - High quality absorption spectroscopy measurements were recently achieved at the
      Sandia National Laboratories Z facility in the soft x-ray range. Detailed
      spectral resolution knowledge is a key requirement for their interpretation. We
      present a methodology for measuring the wavelength dependent crystal spectral
      resolution, with a particular focus on the 7-17 A range. We apply this procedure
      to the case of 1st order resolution of a potassium acid phthalate (KAP) convex
      crystal spectrometer. One calibration issue is that inferring the crystal
      resolution requires that the x-ray source emission feature widths and spectral
      profiles are known. To this aim, we resolve Manson x-ray source Si, Al, and Mg
      Kalpha line profiles using a KAP crystal spectrometer in 2nd order to achieve
      relatively high resolution. This information is exploited to measure 1st order
      KAP resolving powers lambda/Deltalambda~1100-1300 in the 7-10 A wavelength range.

PMID- 23126955
TI  - X-ray grating spectrometer for opacity measurements in the 50 eV to 250 eV
      spectral range at the LULI 2000 laser facility.
AB  - An x-ray grating spectrometer was built in order to measure opacities in the 50
      eV to 250 eV spectral range with an average spectral resolution <E/deltaE> ~ 50.
      It has been used at the LULI-2000 laser facility at Ecole Polytechnique (France)
      to measure the Deltan = 0, n = 3 transitions of several elements with neighboring
      atomic number: Cr, Fe, Ni, and Cu in the same experimental conditions. Hence a
      spectrometer with a wide spectral range is required. This spectrometer features
      one line of sight looking through a heated sample at backlighter emission. It is
      outfitted with one toroidal condensing mirror and several flat mirrors cutting
      off higher energy photons. The spectral dispersion is obtained with a flatfield
      grating. Detection consists of a streak camera sensitive to soft x-ray radiation.
      Some experimental results showing the performance of this spectrometer are
      presented.

PMID- 23126956
TI  - Crosstalk in x-ray framing cameras: Effect on voltage, gain, and timing
      (invited).
AB  - We present evidence that electromagnetic crosstalk between independent strips in
      gated x-ray framing cameras can affect relative gains by up to an order of
      magnitude and gate arrival times up to tens of picoseconds when strip separation
      times are less then ~1 ns. Crosstalk is observed by multiple methods, and it is
      confirmed by direct measurements of voltage on the active surface of the detector
      and also by indirect voltage monitors in routine operation. The voltage
      measurements confirm that crosstalk is produced not only in the active regions of
      the microchannel plate, but also along the entire input path of the voltage
      pulses.

PMID- 23126957
TI  - The x-ray source application test cassette for radiation exposures at the OMEGA
      laser.
AB  - We have designed a sample cassette that can be used to position up to six samples
      in the OMEGA laser chamber. The cassette accommodates round samples up to 38.1 mm
      (1.5(")) in diameter and square samples up to 27 mm on a side, any of which can
      be up to 12.7 mm thick. Smaller specimens are centered with spacers. The test
      cassette allows each sample to have a unique filter scheme, with multiple filter
      regions in front of each sample. This paper will present mechanical design
      considerations and operational aspects of the x-ray source application cassette.

PMID- 23126958
TI  - Radiochromic film measurement of spatial uniformity for a laser generated x-ray
      environment.
AB  - An existing x-ray source application (XRSA) test cassette was modified to hold
      multiple x-ray filter materials followed by two radiochromic film types (FWT-60
      and HD-810 Gafchromic(r) film) to qualitatively characterize the spectral-spatial
      uniformity over the XRSA sample field of view. Multiple sets of film were
      examined and nominal set was determined. These initial, qualitative measurements
      suggest a low-energy regime (E < 3 keV) spatial anisotropy and spatial isotropy
      at higher energies (E > 3 keV).

PMID- 23126959
TI  - Time-resolved soft x-ray spectra from laser-produced Cu plasma.
AB  - The volumetric heating of a thin copper target has been studied with time
      resolved x-ray spectroscopy. The copper target was heated by a plasma produced
      using the Lawrence Livermore National Laboratory's Compact Multipulse Terawatt
      (COMET) laser. A variable spaced grating spectrometer coupled to an x-ray streak
      camera measured soft x-ray emission (800-1550 eV) from the back of the copper
      target to characterize the bulk heating of the target. Radiation hydrodynamic
      simulations were modeled in two-dimensions using the HYDRA code. The target
      conditions calculated by HYDRA were post-processed with the atomic kinetics code
      CRETIN to generate synthetic emission spectra. A comparison between the
      experimental and simulated spectra indicates the presence of specific ionization
      states of copper and the corresponding electron temperatures and ion densities
      throughout the laser-heated copper target.

PMID- 23126960
TI  - Optimization of the configuration of pixilated detectors based on the Shannon
      Nyquist theory.
AB  - The configurations of pixilated detectors for x-ray imaging crystal spectrometers
      and x-ray pinhole cameras can be optimized based on the Shannon-Nyquist sampling
      and interpolation theory, since the observed spectra are typically oversampled.
      The degree of oversampling is quantified and alternative uses for redundant
      pixels are proposed.

PMID- 23126961
TI  - A new interferometry-based electron density fluctuation diagnostic on Alcator C
      Mod.
AB  - The two-color interferometry diagnostic on the Alcator C-Mod tokamak has been
      upgraded to measure fluctuations in the electron density and density gradient for
      turbulence and transport studies. Diagnostic features and capabilities are
      described. In differential mode, fast phase demodulation electronics detect the
      relative phase change between ten adjacent, radially-separated (DeltaR = 1.2 cm,
      adjustable), vertical-viewing chords, which allows for measurement of the line
      integrated electron density gradient. The system can be configured to detect the
      absolute phase shift of each chord by comparison to a local oscillator, measuring
      the line-integrated density. Each chord is sensitive to density fluctuations with
      k(R) < 20.3 cm(-1) and is digitized at up to 10 MS/s, resolving aspects of ion
      temperature gradient-driven modes and other long-wavelength turbulence. Data from
      C-Mod discharges is presented, including observations of the quasi-coherent mode
      in enhanced D-alpha H-mode plasmas and the weakly coherent mode in I-mode.

PMID- 23126962
TI  - Density fluctuation measurements by far-forward collective scattering in the MST
      reversed-field pinch.
AB  - The multichannel polarimeter-interferometer system on the MST reversed-field
      pinch can be utilized to measure far-forward collective scattering from electron
      density fluctuations. The collective scattering system has 11 viewing chords with
      ~8 cm spacing. The source is a 432 MUm (694 GHz) far infrared laser and the
      scattered power is measured using a heterodyne detection scheme. Collective
      scattering provides a line-integrated measurement of fluctuations within the
      divergence of the probe beam covering wavenumber range: k(?) < 1.3 cm(-1),
      corresponding k(?)rho(s) < 1.3 (rho(s) is the ion-sound Larmor radius), the
      region of primary interest for turbulent fluctuation-induced transport. The
      perpendicular wavenumber consists of toroidal, poloidal, and radial
      contributions, which vary with chord position. Coherent modes associated with
      tearing instabilities and neutral-beam driven fast particles are observed along
      with broadband turbulence at frequencies up to 500 kHz. Changes in frequency are
      consistent with a Doppler shift due to parallel plasma flow.

PMID- 23126963
TI  - Recent progress of the HCN interferometer on J-TEXT tokamak.
AB  - A multichannel far-infrared HCN laser interferometer has been developed to
      measure plasma electron density for the J-TEXT tokamak. Initial operation of a
      seven chords system with 7 cm spacing and a 0.1 ms temporal resolution is
      described. Density modulation experiments in J-TEXT show that it is possible to
      obtain information on particle transport by precise measurement of the density
      perturbation amplitude and phase spatial variation. An optical configuration
      upgrade has been implemented in order to improve phase resolution.

PMID- 23126964
TI  - High sensitivity, low noise Mirnov coil array on Prairie View rotamak.
AB  - An array of 32 Mirnov coils with novel features of high sensitivity and low noise
      has been installed on the outside chamber surface of Prairie View rotamak. This
      B(R)-oriented coil array has proven to be very reliable in the plasma driven by
      rotating magnetic field; it can resolve magnetic perturbation signals of 0.1 G.
      With this new diagnostic, the n = 1 tilt, radial shift, and kink modes are
      observed for the first time in rotamak plasmas.

PMID- 23126965
TI  - Development of 3D microwave imaging reflectometry in LHD (invited).
AB  - Three-dimensional (3D) microwave imaging reflectometry has been developed in the
      large helical device to visualize fluctuating reflection surface which is caused
      by the density fluctuations. The plasma is illuminated by the probe wave with
      four frequencies, which correspond to four radial positions. The imaging optics
      makes the image of cut-off surface onto the 2D (7 * 7 channels) horn antenna
      mixer arrays. Multi-channel receivers have been also developed using micro-strip
      line technology to handle many channels at reasonable cost. This system is first
      applied to observe the edge harmonic oscillation (EHO), which is an MHD mode with
      many harmonics that appears in the edge plasma. A narrow structure along field
      lines is observed during EHO.

PMID- 23126966
TI  - First results from the J-TEXT high-resolution three-wave polarimeter
      interferometer.
AB  - A laser-based far-infrared polarimeter-interferometer system utilizing the three
      wave technique has been implemented on the J-TEXT tokamak. The polarimeter
      determines the Faraday effect by measuring the phase difference between two
      collinear, counter-rotating, circularly polarized laser beams. The first results
      of the polarimeter-interferometer designed for J-TEXT have been obtained in the
      most recent J-TEXT experimental campaign. Simultaneous polarimetric and
      interferometric measurement is achieved, with phase resolution up to 0.1 degrees
      , at bandwidth of 50 kHz. The temporal resolution, which is dependent on the
      laser's frequency offset, is ~1 MUs. Continual spatial measurement covering 45 cm
      (80% of the plasma cross-section) is realized by utilizing 1D parabolic beam
      expansion optics. Three initial test chords are installed and future plans call
      for expansion up to 30 chords with 1.5 cm chord spacing, providing high spatial
      resolution for measurement of electron density and current density profiles.
      Reliability of both polarimetric and interferometric measurement is confirmed by
      comparison with computation and data from a hydrocyanic acid (HCN)
      interferometer. With the high temporal and phase resolution, perturbations
      associated with the sawtooth cycle and MHD activity have been observed.

PMID- 23126968
TI  - Core density gradient fluctuation measurement by differential interferometry in
      the helically symmetric experiment stellarator.
AB  - The interferometer system on the Helically Symmetric eXperiment (HSX) stellarator
      uses an expanded beam and linear detector array to realize a multichord
      measurement. Unlike conventional interferometry which determines the plasma phase
      shift with respect to a reference, directly evaluating the phase between two
      adjacent chords can be employed to measure the change in plasma phase with impact
      parameter. This approach provides a measure of the equilibrium density gradient
      or the density gradient fluctuations and is referred to as differential
      interferometry. For central chords, measurements are spatially localized due to a
      geometrical weighting factor and can provide information on core density gradient
      fluctuations. The measurement requires finite coherence between fluctuations in
      the two spatially offset chords. This technique is applied on the HSX stellarator
      to measure both broadband turbulence and coherent modes. Spatial localization is
      exploited to isolate core turbulence changes associated with change in magnetic
      configuration or heating location.

PMID- 23126967
TI  - Temporally resolved plasma composition measurements by collective Thomson
      scattering in TEXTOR (invited).
AB  - Fusion plasma composition measurements by collective Thomson scattering (CTS)
      were demonstrated in recent proof-of-principle measurements in TEXTOR [S. B.
      Korsholm et al., Phys. Rev. Lett. 106, 165004 (2011)]. Such measurements rely on
      the ability to resolve and interpret ion cyclotron structure in CTS spectra.
      Here, we extend these techniques to enable temporally resolved plasma composition
      measurements by CTS in TEXTOR, and we discuss the prospect for such measurements
      with newly installed hardware upgrades for the CTS system on ASDEX Upgrade.

PMID- 23126969
TI  - First results of the SOL reflectometer on Alcator C-Mod.
AB  - A swept-frequency X-mode reflectometer has been built on Alcator C-Mod to measure
      the scrape-off layer (SOL) density profiles adjacent to the lower hybrid
      launcher. The reflectometer system operates between 100 and 146 GHz at sweep
      rates from 10 MUs to 1 ms and covers a density range of ~10(16)-10(20) m(-3) at
      B(0) = 5-5.4 T. This paper discusses the analysis of reflectometer density
      profiles and presents first experimental results of SOL density profile
      modifications due to the application of lower hybrid range-of-frequencies power
      to L-mode discharges. Comparison between density profiles measured by the X-mode
      reflectometer and scanning Langmuir probes is also shown.

PMID- 23126970
TI  - A new frequency-multiplied interferometer system in the GAMMA 10 tandem mirror.
AB  - A new interferometer is installed on the west anchor cell of the GAMMA 10 tandem
      mirror. In GAMMA 10, we have used a heterodyne-type interferometer with a 70-GHz
      IMPATT oscillator and a 150-MHz oscillator for frequency modulation. The new
      interferometer consists of a 17.5-GHz phase locked dielectric resonator
      oscillator and a 37.5-MHz temperature-compensated crystal oscillator, as well as
      frequency multipliers. The main motivation for the new interferometer using
      frequency multipliers is to achieve a stable and cost effective interferometer.
      Direct anchor heating experiments with new anchor ion cyclotron range of
      frequency antennas in both the west and the east anchor cells are carried out.
      Density increases in both anchor cells are clearly observed using the new
      interferometer.

PMID- 23126971
TI  - Design of a correlation electron cyclotron emission diagnostic for Alcator C-Mod.
AB  - A correlation electron cyclotron emission (CECE) diagnostic has been installed in
      Alcator C-Mod. In order to measure electron temperature fluctuations, this
      diagnostic uses a spectral decorrelation technique. Constraints obtained with
      nonlinear gyrokinetic simulations guided the design of the optical system and
      receiver. The CECE diagnostic is designed to measure temperature fluctuations
      which have k(theta) <= 4.8 cm(-1) (k(theta)rho(s) < 0.5) using a well-focused
      beam pattern. Because the CECE diagnostic is a dedicated turbulence diagnostic,
      the optical system is also flexible, which allows for various collimating lenses
      and antenna to be used. The system overview and the demonstration of its
      operability as designed are presented in this paper.

PMID- 23126972
TI  - A field programmable gate array unit for the diagnosis and control of
      neoclassical tearing modes on MAST.
AB  - A real-time system has been developed to trigger both the MAST Thomson scattering
      (TS) system and the plasma control system on the phase and amplitude of
      neoclassical tearing modes (NTMs), extending the capabilities of the original
      system. This triggering system determines the phase and amplitude of a given NTM
      using magnetic coils at different toroidal locations. Real-time processing of the
      raw magnetic data occurs on a low cost field programmable gate array (FPGA) based
      unit which permits triggering of the TS lasers on specific amplitudes and phases
      of NTM evolution. The MAST plasma control system can receive a separate trigger
      from the FPGA unit that initiates a vertical shift of the MAST magnetic axis.
      Such shifts have fully removed m/n = 2/1 NTMs instabilities on a number of MAST
      discharges.

PMID- 23126973
TI  - A 16-channel heterodyne electron cyclotron emission radiometer on J-TEXT.
AB  - To study equilibrium temporal dynamics and the mechanisms of magnetohydrodynamic
      instabilities, a 16-channel heterodyne electron cyclotron emission (ECE)
      radiometer has been developed to view the J-TEXT tokamak from the low field side.
      The ECE radiometer detects second-harmonic extraordinary mode in the frequency
      band of 94-125 GHz which corresponds to resonances from 1.8 T to 2.2 T. This ECE
      system consists of an ECE transmission line, a radio frequency unit, and two 8
      channel intermediate frequency units. An in situ blackbody calibration source is
      applied for system calibration by comparison of hot and cold sources in order to
      provide an absolute temperature measurement.

PMID- 23126974
TI  - Vibration mitigation in J-TEXT far-infrared diagnostic systems.
AB  - Optical structure stability is an important issue for far-infrared (FIR) phase
      measurements. To ensure good signal quality, influence of vibration should be
      minimized. Mechanical amelioration and optical optimization can be taken in turn
      to decrease vibration's influence and ensure acceptable measurement. J-TEXT
      (Joint Texal Experiment Tokamak, formerly TEXT-U) has two FIR diagnostic systems:
      a HCN interferometer system for electron density measurement and a three-wave
      polarimeter-interferometer system (POLARIS) for electron density and Faraday
      effect measurements. All use phase detection techniques. HCN interferometer
      system has almost eliminated the influence of vibration after mechanical
      amelioration and optical optimization. POLARIS also obtained first experimental
      results after mechanical stability improvements and is expected to further reduce
      vibration's influence on Faraday angle to 0.1 degrees  after optical
      optimization.

PMID- 23126975
TI  - Far-infrared polarimetry diagnostic for measurement of internal magnetic field
      dynamics and fluctuations in the C-MOD Tokamak (invited).
AB  - A laser-based (2.55 THz) mulitchord polarimeter is now operational on Alcator C
      Mod and is used to make measurements of the internal magnetic field structure as
      well as plasma fluctuations. The polarimeter is designed to measure the Faraday
      effect for high-field (up to 8.3 T) and high-density (up to 5 * 10(20) m(-3))
      ITER relevant plasma conditions. Initial 3 chord tests are consistent with
      magnetic equilibrium reconstructions and indicate no measurable contamination
      from the toroidal magnetic field due to the Cotton-Mouton effect or misalignment.
      Time response of <1 MUs enables the measurement of fast equilibrium temporal
      dynamics as well as high-frequency fluctuations.

PMID- 23126976
TI  - Design of the reflective optics for Tore Supra ECEI system.
AB  - A 2D electron cyclotron emission (ECE) imaging system for Tore Supra is under
      design for studying the MHD physics of the magnetically confined plasma such as
      sawteeth, tearing modes, and turbulent fluctuations. Complex beam path due to the
      tight access in Tore Supra led to the design of reflective optics made of 6 or
      more large cylindrical/flat mirrors. The total path length of the ECE beam is
      about 11 m, including almost 4 m inside the vacuum vessel. The imaging property
      of the optics has been estimated using the Gaussian beam simulation and ray
      transfer analysis. The possible setups for the optical alignment of the
      diagnostic and the operation scenarios with single- or dual-array measurement
      system are discussed.

PMID- 23126977
TI  - Pedestal magnetic field measurements using a motional Stark effect polarimeter.
AB  - Temperature-controlled, 0.15 nm interference filters were installed on an edge
      viewing system of the motional Stark effect (MSE) polarimeter on the DIII-D
      tokamak. The upgraded system provides a factor of two reduction in the bandpass
      compared to the previous design, and linear control of the bandpass, which is
      unaltered by wavelength tuning. With the new system, there is a reduced
      dependence of the inferred polarization angle on the filter wavelength
      calibration. Recent measurements from the calibrated edge-viewing system show
      increased agreement with other MSE arrays.

PMID- 23126978
TI  - Collinearity alignment of probe beams in a laser-based Faraday effect diagnostic.
AB  - Two counter-rotating circularly polarized beams are used in a laser-based
      polarimetry diagnostic providing a phase measurement of the Faraday effect.
      Collinearity of these beams is a key issue that affects measurement accuracy.
      Spatial offset from even small misalignment induces systematic error due to
      density gradient and path length difference. Here, we report an alignment
      technique using a rotating dielectric wedge, which is capable of reducing spatial
      offset of two probe beams below 0.1 mm for beams with 40 mm diameter. With
      optimized alignment, 0.05 degrees  Faraday effect fluctuations associated with
      global tearing modes are resolved with an uncertainty below 0.01 degrees .

PMID- 23126979
TI  - Design of a millimeter-wave polarimeter for NSTX-Upgrade and initial test on DIII
      D.
AB  - Polarimetry is a powerful diagnostic technique to probe plasma equilibria and
      magnetic fluctuations in fusion plasmas. In a high beta plasma such as the
      National Spherical Torus eXperiment (NSTX), these measurements are important to
      understand plasma stability and anomalous transport. A 288 GHz polarimeter
      operating along a major radial chord in retroreflection geometry has been
      developed and is being tested on the DIII-D tokamak to prepare for future
      implementation on NSTX-Upgrade. The system launches a rotating linearly polarized
      beam and detects the phase shift directly related to the polarization change
      caused by the plasma. To accomplish this, a pair of orthogonal linearly polarized
      beams with a stable difference frequency is generated using a single sideband
      modulation technique, then combined and transformed to be counter-rotating
      circularly polarized. To improve phase resolution, quasi-optical isolation, using
      Faraday rotators and polarizers, is utilized to eliminate a multi-path feedback
      effect, which is found to be the primary source of phase error. The bench tests
      in the laboratory and DIII-D power supply test discharges indicate <=1 degrees 
      phase resolution.

PMID- 23126980
TI  - Microwave Doppler reflectometer system in LHD.
AB  - In order to measure the poloidal rotation velocity, a Doppler reflectometer has
      been developed in Large Helical Device (LHD). A remotely controlled antenna
      tilting system has been installed in an LHD vacuum vessel. A synthesizer is used
      as the source, and the operation microwave frequency ranges are ka-band and V
      band. In LHD last experimental campaign we obtained the Doppler shifted signal,
      which was consistent with CXRS measurements.

PMID- 23126981
TI  - Thomson scattering diagnostic for the measurement of ion species fraction.
AB  - Simultaneous Thomson scattering measurements of collective electron-plasma and
      ion-acoustic fluctuations have been utilized to determine ion species fraction
      from laser produced CH plasmas. The CH(2) foil is heated with 10 laser beams, 500
      J per beam, at the Omega Laser facility. Thomson scattering measurements are made
      4 mm from the foil surface using a 30 J 2omega probe laser with a 1 ns pulse
      length. Using a series of target shots the plasma evolution is measured from 2.5
      ns to 9 ns after the rise of the heater beams. Measuring the electron density and
      temperature from the electron-plasma fluctuations constrains the fit of the two
      ion species theoretical form factor for the ion feature such that the ion
      temperature, plasma flow velocity and ion species fraction are determined. The
      ion species fraction is determined to an accuracy of +/-0.06 in species fraction.

PMID- 23126982
TI  - Improvements to the calibration of the MST Thomson scattering diagnostic.
AB  - Calibration of the Madison Symmetric Torus Thomson scattering system has been
      refined to improve temperature fluctuation measurements. Multiple avalanche
      photodiodes have been directly calibrated for use as reference detectors during
      calibration, improving accuracy and ease of use. From the absolute calibration we
      calculate corrections to the gain for variation in detector operating
      temperature. We also measure the spatial uniformity of detector responsivity for
      several photodiodes, and present a method of accounting for non-uniformity in the
      calibration process. Finally, the gain and noise enhancement are measured at
      multiple wavelengths to improve temperature and uncertainty measurements.

PMID- 23126983
TI  - Modification of ordinary-mode reflectometry system to detect lower-hybrid waves
      in Alcator C-Mod.
AB  - Backscattering experiments to detect lower-hybrid (LH) waves have been performed
      in Alcator C-Mod, using the two modified channels (60 GHz and 75 GHz) of an
      ordinary-mode reflectometry system with newly developed spectral recorders that
      can continuously monitor spectral power at a target frequency. The change in the
      baseline of the spectral recorder during the LH wave injection is highly
      correlated to the strength of the X-mode non-thermal electron cyclotron emission.
      In high density plasmas where an anomalous drop in the lower hybrid current drive
      efficiency is observed, the observed backscattered signals are expected to be
      generated near the last closed flux surface, demonstrating the presence of LH
      waves within the plasma. This experimental technique can be useful in identifying
      spatially localized LH electric fields in the periphery of high-density plasmas.

PMID- 23126984
TI  - Design of the polarization multi-pass Thomson scattering system.
AB  - A novel configuration of the multi-pass Thomson scattering (TS) system is
      proposed to improve the time resolution and accuracy of electron temperature
      measurements by use of a polarization control technique. This configuration can
      realize a perfect coaxial multi-passing at each pass, and the number of round
      trips is not limited by the optical configuration. To confirm the feasibility of
      the new method, we installed this system in the GAMMA 10 plasma system. As a
      result, the integrated scattering signal of the double-pass configuration is
      about two times larger than that of the single-pass configuration. These results
      are in good agreement with the design.

PMID- 23126985
TI  - First results from EBW emission diagnostics on COMPASS.
AB  - COMPASS tokamak shots at low magnetic field feature overdense plasmas during the
      extended current flat-top phase. The first harmonic of the electron cyclotron
      emission is completely cutoff for O and X modes and so the emission caused by
      electron Bernstein waves (EBWs) propagating obliquely with respect to the
      magnetic field and undergoing so called EBW-X-O conversion process can be
      observed. We perform an angular scan of the EBW emission during a set of
      comparable shots in order to determine the optimum antenna direction. A weak
      dependence of the radiative temperature on the antenna angles indicates an
      influence of multiple reflections from the vessel wall. The low temperature at
      the mode conversion region is responsible for the collisional damping of EBW,
      which can explain several times lower measured radiative temperature than the
      electron temperature measured by the Thomson scattering system.

PMID- 23126986
TI  - Polychromator for the edge Thomson scattering system in ITER.
AB  - A new type polychromator has been designed for the edge Thomson scattering system
      in ITER. Signal light is parallelly dispersed into two parts at the first
      interference filter. Spectral transmissivities for some spectral channels may
      enhance better than the conventional type polychromator. In the new type
      polychromator, the misalignment due to the machine accuracy is expected to be
      within the margin of APD area. In order to calibrate the spectral transmissivity
      using the dual-laser injection method during the plasma discharge, it is
      preferred that the spectral channels are separated at the geometric mean of the
      injected two wavelengths.

PMID- 23126987
TI  - ECE-imaging of the H-mode pedestal (invited).
AB  - A synthetic diagnostic has been developed that reproduces the highly structured
      electron cyclotron emission (ECE) spectrum radiated from the edge region of H
      mode discharges. The modeled dependence on local perturbations of the equilibrium
      plasma pressure allows for interpretation of ECE data for diagnosis of local
      quantities. Forward modeling of the diagnostic response in this region allows for
      improved mapping of the observed fluctuations to flux surfaces within the plasma,
      allowing for the poloidal mode number of coherent structures to be resolved. In
      addition, other spectral features that are dependent on both T(e) and n(e)
      contain information about pedestal structure and the electron energy distribution
      of localized phenomena, such as edge filaments arising during edge-localized mode
      (ELM) activity.

PMID- 23126988
TI  - A compact multichannel spectrometer for Thomson scattering.
AB  - The availability of high-efficiency volume phase holographic (VPH) gratings and
      intensified CCD (ICCD) cameras have motivated a simplified, compact spectrometer
      for Thomson scattering detection. Measurements of T(e) < 100 eV are achieved by a
      2971 l/mm VPH grating and measurements T(e) > 100 eV by a 2072 l/mm VPH grating.
      The spectrometer uses a fast-gated (~2 ns) ICCD camera for detection. A Gen III
      image intensifier provides ~45% quantum efficiency in the visible region. The
      total read noise of the image is reduced by on-chip binning of the CCD to match
      the 8 spatial channels and the 10 spectral bins on the camera. Three
      spectrometers provide a minimum of 12 spatial channels and 12 channels for
      background subtraction.

PMID- 23126989
TI  - 2D full wave modeling for a synthetic Doppler backscattering diagnostic.
AB  - Doppler backscattering (DBS) is a plasma diagnostic used in tokamaks and other
      magnetic confinement devices to measure the fluctuation level of intermediate
      wavenumber (k(theta)rho(s) ~ 1) density fluctuations and the lab frame
      propagation velocity of turbulence. Here, a synthetic DBS diagnostic is
      described, which has been used for comparisons between measurements in the DIII-D
      tokamak and predictions from nonlinear gyrokinetic simulations. To estimate the
      wavenumber range to which a Gaussian beam would be sensitive, a ray tracing code
      and a 2D finite difference, time domain full wave code are used. Experimental
      density profiles and magnetic geometry are used along with the experimental
      antenna and beam characteristics. An example of the effect of the synthetic
      diagnostic on the output of a nonlinear gyrokinetic simulation is presented.

PMID- 23126990
TI  - Design and implementation of a multichannel millimeter wave interferometer for
      the Compact Toroidal Hybrid experiment.
AB  - A three-channel 1 mm wave interferometer has been designed, assembled, and
      installed on the Compact Toroidal Hybrid torsatron (CTH). The interferometer
      design makes novel use of a subharmonic mixer for detection, which simplifies
      alignment. It employs a single electronically tunable source that is repetitively
      chirped using a sawtooth waveform of frequency up to 1 MHz. The 15.25 GHz drive
      oscillator is multiplied in two stages to 122 GHz before a final doubler stage
      brings it to 244 GHz. Local oscillator (LO) power at 122 GHz is directed through
      waveguide to the LO input of the subharmonic mixer of each viewing chord,
      simplifying alignment. Phase detection is performed by directly digitizing the
      amplified mixer outputs at 50 MHz and processing them with a software algorithm.
      Initial measurements made with the central chord of the new interferometer agree
      with those from the existing 4 mm system at low densities. The 1 mm system
      performs well in current-driven discharges reaching densities over 10(19) m(-3),
      whereas the lower frequency interferometer is found to be less reliable due to
      loss of fringes. This is a critical improvement for experiments studying the
      onset, avoidance, and vacuum magnetic transform dependence of disruptions in the
      CTH device.

PMID- 23126991
TI  - Development of polarization-controlled multi-pass Thomson scattering system in
      the GAMMA 10 tandem mirror.
AB  - In the GAMMA 10 tandem mirror, the typical electron density is comparable to that
      of the peripheral plasma of torus-type fusion devices. Therefore, an effective
      method to increase Thomson scattering (TS) signals is required in order to
      improve signal quality. In GAMMA 10, the yttrium-aluminum-garnet (YAG)-TS system
      comprises a laser, incident optics, light collection optics, signal detection
      electronics, and a data recording system. We have been developing a multi-pass TS
      method for a polarization-based system based on the GAMMA 10 YAG TS. To evaluate
      the effectiveness of the polarization-based configuration, the multi-pass system
      was installed in the GAMMA 10 YAG-TS system, which is capable of double-pass
      scattering. We carried out a Rayleigh scattering experiment and applied this
      double-pass scattering system to the GAMMA 10 plasma. The integrated scattering
      signal was made about twice as large by the double-pass system.

PMID- 23126992
TI  - Conceptual design of new polychromator on Thomson scattering system to measure
      Zeff.
AB  - To measure the Z(eff) with electron temperature (T(e)) and electron density
      (n(e)) profiles at the same time and the same position in the KSTAR tokamak, we
      design a new polychromator for Thomson scattering system that has additional
      function. The additional function is measuring bremsstrahlung intensity to
      calculate Z(eff) independent of Thomson signals. For this new polychromator, we
      design and fabricate a collimation lens set, and interference filter that has
      center wavelength of 523 nm and 2 nm FWHM. Finally, we change the lenses,
      detector diodes, and add the bremsstrahlung filter on the KSTAR edge Thomson
      scattering polychromator. Then this new polychromator was tested by Tungsten
      light and monochromator.

PMID- 23126993
TI  - A Thomson scattering diagnostic on the Pegasus Toroidal experiment.
AB  - By exploiting advances in high-energy pulsed lasers, volume phase holographic
      diffraction gratings, and image intensified CCD cameras, a new Thomson scattering
      system has been designed to operate from 532 - 592 nm on the Pegasus Toroidal
      Experiment. The system uses a frequency-doubled, Q-switched Nd:YAG laser
      operating with an energy of 2 J at 532 nm and a pulse duration of 7 ns FWHM. The
      beam path is < 7m, the beam diameter remains <= 3 mm throughout the plasma, and
      the beam dump and optical baffling is located in vacuum but can be removed for
      maintenance by closing a gate valve. A custom lens system collects scattered
      photons from 15 cm < R(maj) < 85 cm at ~F/6 with 14 mm radial resolution. Initial
      measurements will be made at 12 spatial locations with 12 simultaneous background
      measurements at corresponding locations. The estimated signal at the machine-side
      collection optics is ~3.5 * 10(4) photons for plasma densities of 10(19) m(-3).
      Typical plasmas measured will range from densities of mid-10(18) to mid-10(19) m(
      3) with electron temperatures from 10 to 1000 eV.

PMID- 23126994
TI  - Multi-channel far-infrared HL-2A interferometer-polarimeter.
AB  - An HL-2A interferometer is upgraded to a multi-channel
      interferometer/polarimeter, which includes four chords for the interferometer and
      four chords for the polarimeter. The far-infrared lasers (at lambda = 432.5 MUm
      and 30 mW power) are used to probe plasmas horizontally in the midplane of HL-2A.
      A conventional heterodyne technique is used for the interferometer. Two counter
      rotating circularly polarized waves are used to measure the Faraday rotation
      effect. A fast-phase comparator with temporal resolution of 1 MUs and phase
      resolution 0.1 degrees  is developed. Further, the distortion of the polarization
      caused by the beam-splitters and the other optical components is also
      investigated.

PMID- 23126995
TI  - Elevation angle alignment of quasi optical receiver mirrors of collective Thomson
      scattering diagnostic by sawtooth measurements.
AB  - Localized measurements of the fast ion velocity distribution function and the
      plasma composition measurements are of significant interest for the fusion
      community. Collective Thomson scattering (CTS) diagnostics allow such
      measurements with spatial and temporal resolution. Localized measurements require
      a good alignment of the optical path in the transmission line. Monitoring the
      alignment during the experiment greatly benefits the confidence in the CTS
      measurements. An in situ technique for the assessment of the elevation angle
      alignment of the receiver is developed. Using the CTS diagnostic on TEXTOR
      without a source of probing radiation in discharges with sawtooth oscillations,
      an elevation angle misalignment of 0.9 degrees  was found with an accuracy of
      0.25 degrees .

PMID- 23126997
TI  - Electron density and temperature profile diagnostics for C-2 field reversed
      configuration plasmas.
AB  - The 9-point Thomson scattering diagnostic system for the C-2 field reversed
      configuration plasmas is improved and the measured electron temperature profiles
      are consistent with theoretical expectations. Rayleigh scattering revealed a
      finite line width of the ruby laser emission, which complicates density
      calibration. Taking advantage of the plasma wobble motion, density profile
      reconstruction accuracy from the 6-chord two-color CO(2)/HeNe interferometer data
      is improved.

PMID- 23126996
TI  - Evaluation of the operating space for density fluctuation measurements employing
      2D imaging reflectometry.
AB  - Microwave imaging reflectometry provides broad poloidal coverage as a density
      fluctuation measurement tool. 2D imaging systems are evaluated for DIII-D
      relevant conditions using a full-wave reflectometer code, FWR2D. Reasonable
      correlation of the synthetic diagnostic signal with density fluctuations at the
      plasma cutoff surface for a wide range of fluctuation parameters is evaluated and
      achieved for coherent oscillations; also the frequency spectra are compared for
      relevant fluctuations. The consequences of non-idealities inherent to imaging
      fluctuations away from the plasma midplane, where receiving antennas view the
      plasma cutoff at oblique angles, are evaluated for the optimization of these
      systems.

PMID- 23126998
TI  - Extension of the measurable temperature range of the LHD Thomson scattering
      system.
AB  - The large helical device Thomson scattering system was designed for the target
      electron temperature (T(e)) range, T(e) = 50 eV-10 keV. Above 10 keV, the
      experimental error becomes rapidly worse. In order to obtain reliable T(e) data
      in the temperature range above 10 keV, we are planning to extend the measurable
      T(e) range by following two methods. First we have installed one more wavelength
      channel that observes shorter wavelength region in polychromators. Next applying
      forward scattering configuration is another candidate. We estimate the data
      quality when the two methods are used. Both of the two methods are expected to
      improve T(e) data quality at T(e) >= 10 keV.

PMID- 23126999
TI  - Development of frequency modulation reflectometer for KSTAR tokamak: data
      analysis based on Gaussian derivative wavelet.
AB  - A frequency modulation reflectometer has been developed to measure the density
      profile of the KSTAR tokamak. It has two channels operating in X-mode in the
      frequency range of Q band (33-50 GHz) and V band (50-75 GHz). The full band is
      swept in 20 MUs. The mixer output is directly digitized at the sampling rate of
      100 MSamples/s. A new phase detection algorithm is developed to analyze both
      amplitude and frequency modulated signal. The algorithm is benchmarked for a
      synthesized amplitude modulation-frequency modulation signal. This new algorithm
      is applied to the data analysis of KSTAR reflectometer.

PMID- 23127000
TI  - Initial results of the high resolution edge Thomson scattering upgrade at DIII-D.
AB  - Validation of models of pedestal structure is an important part of predicting
      pedestal height and performance in future tokamaks. The Thomson scattering
      diagnostic at DIII-D has been upgraded in support of validating these models.
      Spatial and temporal resolution, as well as signal to noise ratio, have all been
      specifically enhanced in the pedestal region. This region is now diagnosed by 20
      view-chords with a spacing of 6 mm and a scattering length of just under 5 mm
      sampled at a nominal rate of 250 Hz. When mapped to the outboard midplane, this
      corresponds to ~3 mm spacing. These measurements are being used to test critical
      gradient models, in which pedestal gradients increase in time until a threshold
      is reached. This paper will describe the specifications of the upgrade and
      present initial results of the system.

PMID- 23127001
TI  - Development of a YAG laser system for the edge Thomson scattering system in ITER.
AB  - A prototype YAG laser system for the edge Thomson scattering system in ITER has
      been newly developed. Performance of the laser amplifier was improved by using
      flow tubes made of samarium-doped glass; the small signal gain reached 20 at its
      maximum. As a result, an output energy of 7.66 J at 100 Hz was successfully
      achieved, and the performance exceeded the target performance (5 J, 100 Hz).

PMID- 23127002
TI  - Identification of errors in the electron density measurements of a tangential
      interferometer/polarimeter system during a tokamak discharge.
AB  - A new method for the comparative verification of electron density measurements
      obtained with a tangential interferometer and a polarimeter during a discharge is
      proposed. The possible errors associated with the interferometer and polarimeter
      are classified by the time required for their identification. Based on the
      characteristics of the errors, the fringe shift error of the interferometer and
      the low-frequency noise of the polarimeter were identified and corrected for the
      JT-60U tangential interferometer/polarimeter system.

PMID- 23127003
TI  - Anisotropic electron temperature measurements without knowing the spectral
      transmissivity for a JT-60SA Thomson scattering diagnostic.
AB  - This paper focuses on a method for measuring the electron temperature (T(e))
      without knowing the transmissivity using Thomson scattering diagnostic with a
      double-pass scattering system. Application of this method for measuring the
      anisotropic T(e), i.e., the T(e) in the directions parallel (T(eparallel)) and
      perpendicular (T(eperpendicular)) to the magnetic field, is proposed. Simulations
      based on the designed parameters for a JT-60SA indicate the feasibility of the
      measurements except in certain T(e) ranges, e.g., T(eparallel) ~
      3.5T(eperpendicular) at 120 degrees  of the scattering angle.

PMID- 23127004
TI  - Development of leaky-wave antenna for digitally controlled millimeter-wave
      interferometer.
AB  - We propose a new interferometer concept that can realize electron-density
      distribution measurement with high spatial and moderate temporal resolution. The
      image non-radiative dielectric guide antenna can probe a wide measurement area
      simultaneously. We fabricated the antenna with an electromagnetic simulator and
      confirmed that the simulated and measured radiation patterns are consistent with
      each other. In addition, we found that the antenna shows the required
      characteristics such as scanning characteristics, which depend on the input
      frequency.

PMID- 23127005
TI  - Simultaneous imaging electron- and ion-feature Thomson scattering measurements of
      radiatively heated Xe.
AB  - Uniform density and temperature Xe plasmas have been produced over >4 mm scale
      lengths using x-rays generated in a cylindrical Pb cavity. The cavity is 750 MUm
      in depth and diameter, and is heated by a 300 J, 2 ns square, 1054 nm laser pulse
      focused to a spot size of 200 MUm at the cavity entrance. The plasma is
      characterized by simultaneous imaging Thomson scattering measurements from both
      the electron and ion scattering features. The electron feature measurement
      determines the spatial electron density and temperature profile, and using these
      parameters as constraints in the ion feature analysis allows an accurate
      determination of the charge state of the Xe ions. The Thomson scattering probe
      beam is 40 J, 200 ps, and 527 nm, and is focused to a 100 MUm spot size at the
      entrance of the Pb cavity. Each system has a spatial resolution of 25 MUm, a
      temporal resolution of 200 ps (as determined by the probe duration), and a
      spectral resolution of 2 nm for the electron feature system and 0.025 nm for the
      ion feature system. The experiment is performed in a Xe filled target chamber at
      a neutral pressure of 3-10 Torr, and the x-rays produced in the Pb ionize and
      heat the Xe to a charge state of 20+/-4 at up to 200 eV electron temperatures.

PMID- 23127006
TI  - A reflective optical transport system for ultraviolet Thomson scattering from
      electron plasma waves on OMEGA.
AB  - A reflective optical transport system has been designed for the OMEGA Thomson
      scattering diagnostic. A Schwarzschild objective that uses two concentric
      spherical mirrors coupled to a Pfund objective provides diffraction-limited
      imaging across all reflected wavelengths. This enables the operator to perform
      Thomson-scattering measurements of ultraviolet (0.263 MUm) light scattered from
      electron plasma waves.

PMID- 23127007
TI  - High-resolution Thomson scattering system on the COMPASS tokamak: evaluation of
      plasma parameters and error analysis.
AB  - The electron density and temperature profiles measured by the Thomson scattering
      diagnostic on the COMPASS tokamak are used for estimation of electron kinetic
      energy, energy confinement time, and effective charge number Z(eff). Data are
      compared with the line-integrated electron density measured by a microwave
      interferometer in an ohmically heated plasma with a circular cross section. An
      error analysis of both electron temperature and density are performed by two
      methods-a constant chi-square boundaries method and a Monte Carlo simulation,
      determining asymmetrical error bars for the electron temperature.

PMID- 23127008
TI  - Soft x-ray backlighting of direct-drive implosions using a spherical crystal
      imager on OMEGA.
AB  - Using a spherically bent quartz crystal for the Si He(alpha) line at ~1.865 keV,
      a narrowband x-ray imager has been deployed at the Omega Laser Facility to record
      backlit images of direct-drive laser implosions. The crystal was cut along the
      1011 planes for a 2d spacing of 0.687 nm, resulting in a Bragg angle of 83.9
      degrees . Apertures in front of the crystal were used to control the astigmatism
      of the imaging system. The backlit images show a high signal-to-background ratio
      of >10:1 with backlighter laser energies >=1.5 kJ at a 10-ps pulse duration and a
      spatial resolution of better than 20 MUm.

PMID- 23127009
TI  - Tangential x-ray imaging crystal spectrometer on J-TEXT tokamak.
AB  - A tangential x-ray imaging crystal spectrometer (XICS) has been developed for the
      J-TEXT tokamak to measure the ion temperature and the plasma toroidal rotation
      velocity. The resonance spectral line and its satellites of Ar XVII in the ranges
      of 3.94 A-4.0 A are detected. A spherically bent quartz crystal with 2d = 4.913 A
      is used in this system. The crystal has a dimension of 9 cm high and 3 cm wide
      and the radius of curvature 3823 mm. The XICS is designed to receive emission of
      Ar XVII from -10 cm to +10 cm region with a spatial resolution of 3.1 cm in the
      vertical direction considering the parameters of the J-TEXT plasma. The XICS has
      a tangential angle of 27 degrees  with respect to toroidal direction in the
      magnetic axis. A two-dimensional 100 mm by 300 mm multi-wire proportional counter
      is applied to detect the spectra.

PMID- 23127010
TI  - Tomographic imaging system for measuring impurity line emission in a field
      reversed configuration.
AB  - A 16 chord optical tomography system has been developed and implemented in the
      flux coil generated-field reversed configuration (FRC). The chords are arranged
      in two fans of eight, which cover ~35% of the vessel area at the midplane. Each
      illuminate separate photomultiplier tubes (PMTs) which are fitted with narrow
      band-pass filters. In this case, filters are centered at 434.8 nm to measure
      emission from singly ionized argon. PMT crosstalk is negligible. Background noise
      due to electron radiation and H(gamma) line radiation is <10% of argon emission.
      The spatial resolution of the reconstruction is 1.5 cm. Argon is introduced using
      a puff valve and tube designed to impart the gas into the system as the FRC is
      forming. Reconstruction of experimental data results in time-dependent, 2D
      emissivity profiles of the impurity ions. Analysis of these data show radial,
      cross-field diffusion to be in the range of 10-10(3) m(2)/s during FRC
      equilibrium.

PMID- 23127011
TI  - Simultaneous high-resolution two-dimensional spatial and one-dimensional
      picosecond streaked x-ray pinhole imaging.
AB  - A Kentech x-ray streak camera was run at the LLNL compact multipulse terawatt
      (COMET) laser to record simultaneous space- and time-resolved measurements of
      picosecond laser-produced plasmas. Four different x-ray energy channels were
      monitored using broadband filters to record the time history of Cu targets heated
      at irradiances of 10(16)-10(19) W/cm(2). Through the Cu filter channel, a time
      resolution below 3 ps was obtained. Additionally, an array of 10 MUm diameter
      pinholes was placed in front of the camera to produce multiple time-resolved x
      ray images on the photocathode and time-integrated images on the phosphor with 10
      and 15 times magnification, respectively, with spatial resolution of < 13 MUm.

PMID- 23127012
TI  - Low cost alternative of high speed visible light camera for tokamak experiments.
AB  - We present design, analysis, and performance evaluation of a new, low cost and
      high speed visible-light camera diagnostic system for tokamak experiments. The
      system is based on the camera Casio EX-F1, with the overall price of
      approximately a thousand USD. The achieved temporal resolution is up to 40 kHz.
      This new diagnostic was successfully implemented and tested at the university
      tokamak GOLEM (R = 0.4 m, a = 0.085 m, B(T) < 0.5 T, I(p) < 4 kA). One possible
      application of this new diagnostic at GOLEM is discussed in detail. This
      application is tomographic reconstruction for estimation of plasma position and
      emissivity.

PMID- 23127013
TI  - Thermo-mechanical analysis of ITER first mirrors and its use for the ITER
      equatorial visible/infrared wide angle viewing system optical design.
AB  - ITER first mirrors (FMs), as the first components of most ITER optical
      diagnostics, will be exposed to high plasma radiation flux and neutron load. To
      reduce the FMs heating and optical surface deformation induced during ITER
      operation, the use of relevant materials and cooling system are foreseen. The
      calculations led on different materials and FMs designs and geometries (100 mm
      and 200 mm) show that the use of CuCrZr and TZM, and a complex integrated cooling
      system can limit efficiently the FMs heating and reduce their optical surface
      deformation under plasma radiation flux and neutron load. These investigations
      were used to evaluate, for the ITER equatorial port visible/infrared wide angle
      viewing system, the impact of the FMs properties change during operation on the
      instrument main optical performances. The results obtained are presented and
      discussed.

PMID- 23127014
TI  - Diagnosing radiative shocks from deuterium and tritium implosions on NIF.
AB  - During the recent ignition tuning campaign at the National Ignition Facility,
      layered cryogenic deuterium and tritium capsules were imploded via x-ray driven
      ablation. The hardened gated x-ray imager diagnostic temporally and spatially
      resolves the x-ray emission from the core of the capsule implosion at energies
      above ~8 keV. On multiple implosions, ~200-400 ps after peak compression a
      spherically expanding radiative shock has been observed. This paper describes the
      methods used to characterize the radial profile and rate of expansion of the
      shock induced x-ray emission.

PMID- 23127015
TI  - Hard x-ray (>100 keV) imager to measure hot electron preheat for indirectly
      driven capsule implosions on the NIF.
AB  - We have fielded a hard x-ray (>100 keV) imager with high aspect ratio pinholes to
      measure the spatially resolved bremsstrahlung emission from energetic electrons
      slowing in a plastic ablator shell during indirectly driven implosions at the
      National Ignition Facility. These electrons are generated in laser plasma
      interactions and are a source of preheat to the deuterium-tritium fuel. First
      measurements show that hot electron preheat does not limit obtaining the fuel
      areal densities required for ignition and burn.

PMID- 23127016
TI  - Radial profile measurement of electron temperature in edge stochastic magnetic
      field layer of LHD using intensity ratio of extreme ultraviolet line emissions.
AB  - Vertical profile of neon line emissions in 30-650 A wavelength range has been
      observed in horizontally elongated plasma cross section of Large Helical Device
      (LHD). Intensity ratio between the neon line emissions is studied to measure the
      radial profile of electron temperature in the edge stochastic magnetic field
      layer of LHD. The edge temperature profile successfully obtained from the line
      ratio of NeVIII 2s-3p to 2p-3s transitions is compared with the simulation based
      on three-dimensional edge transport code. The result shows a reasonably good
      agreement with the edge temperature profile analyzed from atomic data and
      analysis structure code. The electron temperature at last closed flux surface
      measured from the intensity ratio is also in good agreement with that measured
      from Thomson scattering.

PMID- 23127017
TI  - Towards hard x-ray imaging at GHz frame rate.
AB  - Gigahertz (GHz) imaging using hard x-rays (> or approximately equal to 10 keV)
      can be useful to high-temperature plasma experiments, as well as research and
      applications using coherent photons from synchrotron radiation and x-ray free
      electron lasers. GHz framing rate can be achieved by using multiple cameras
      through multiplexing. The advantages and trade-offs of single-photon detection
      mode, when no more than one x-ray photon is detected per pixel, are given. Two
      possible paths towards x-ray imaging at GHz frame rates using a single camera
      are: (a) avalanche photodiode arrays of high-Z materials and (b) microchannel
      plate photomultipliers in conjunction with materials with large indices of
      refraction.

PMID- 23127018
TI  - Dual transmission grating based imaging radiometer for tokamak edge and divertor
      plasmas.
AB  - The designs of single transmission grating based extreme ultraviolet (XUV) and
      vacuum ultraviolet (VUV) imaging spectrometers can be adapted to build an imaging
      radiometer for simultaneous measurement of both spectral ranges. This paper
      describes the design of such an imaging radiometer with dual transmission
      gratings. The radiometer will have an XUV coverage of 20-200 A with a ~10 A
      resolution and a VUV coverage of 200-2000 A with a ~50 A resolution. The
      radiometer is designed to have a spatial view of 16 degrees , with a 0.33 degrees
      resolution and a time resolution of ~10 ms. The applications for such a
      radiometer include spatially resolved impurity monitoring and electron
      temperature measurements in the tokamak edge and the divertor. As a proof of
      principle, the single grating instruments were used to diagnose a low temperature
      reflex discharge and the relevant data is also included in this paper.

PMID- 23127019
TI  - Design and fabrication of a multi-purpose soft x-ray array diagnostic system for
      KSTAR.
AB  - A multi-purpose soft x-ray array diagnostic system was developed for measuring
      two-dimensional x-ray emissivity profile, electron temperature, Ar impurity
      transport, and total radiation power. A remotely controlled filter wheel was
      designed with three different choices of filters. The electron temperature
      profile can be determined from the ratio of two channels having different
      thickness of Be layer, and the Ar impurity concentration transport can be
      determined from a pair of Ar Ross filters (CaF(2) and NaCl thin films). Without
      any filters, this diagnostic system can also be used as a bolometer.

PMID- 23127020
TI  - High speed vacuum ultraviolet telescope system for edge fluctuation measurement
      in the large helical device.
AB  - A high speed tangentially viewing vacuum ultraviolet telescope system has been
      developed in the Large Helical Device (LHD), with the aim of investigating edge
      MHD activities. The spatial structure of low frequency (~0.75 kHz) MHD activity
      with poloidal/toroidal mode numbers of m/n = 1/1 has been measured with this
      diagnostic.

PMID- 23127021
TI  - Restoring transmission of irradiated image fiber bundles.
AB  - Image fiber bundles are employed in fusion experiments and other high radiation
      environments where they are used to transmit an image from an unprotected
      objective lens to a radiation shielded camera. Due to their exposure to neutron
      and gamma radiation the transmission of these expensive image fiber bundles can
      rapidly degrade, especially at the shorter visible wavelengths, and require
      costly replacement. A cost-effective, non-destructive heat treatment process in
      which entire fiber bundles are heated gradually in air to 150 degrees -200
      degrees C and held for tens of hours has been shown to recover much of the
      transmission lost due to the radiation induced absorption. The restoration
      process can be repeated multiple times without a loss in effectiveness, although
      some physical degradation of inter-fiber alignment has been observed. The results
      and the apparatus used for the successful restoration of the transmission of
      multiple image fiber bundles across their entire wavelength band will be
      presented.

PMID- 23127022
TI  - Feasibility of characterizing laser-ablated carbon plasmas via planar laser
      induced fluorescence.
AB  - Planar laser induced fluorescence (PLIF) imaging can potentially assess ion
      distributions and coupling in the context of super-Alfvenic ablation plasma
      expansions into magnetized background plasmas. In this feasibility study, we
      consider the application of PLIF to rapidly expanding carbon plasmas generated
      via energetic laser ablation of graphite. By utilizing hydrodynamic and
      collisional-radiative simulations, we identify schemes accessible to commercially
      available tunable lasers for the C I atom, the C II ion, and the C V ion. We then
      estimate the signal-to-noise ratios yielded by the schemes under reasonable
      experimental configurations.

PMID- 23127023
TI  - A multi-frame soft x-ray pinhole imaging diagnostic for single-shot applications.
AB  - For high energy density magnetized target fusion experiments at the Air Force
      Research Laboratory FRCHX machine, obtaining multi-frame soft x-ray images of the
      field reversed configuration (FRC) plasma as it is being compressed will provide
      useful dynamics and symmetry information. However, vacuum hardware will be
      destroyed during the implosion. We have designed a simple in-vacuum pinhole
      nosecone attachment, fitting onto a Conflat window, coated with 3.2 mg/cm(2) of P
      47 phosphor, and covered with a thin 50-nm aluminum reflective overcoat, lens
      coupled to a multi-frame Hadland Ultra intensified digital camera. We compare
      visible and soft x-ray axial images of translating (~200 eV) plasmas in the FRX-L
      and FRCHX machines in Los Alamos and Albuquerque.

PMID- 23127025
TI  - Compact Kirkpatrick-Baez microscope mirrors for imaging laser-plasma x-ray
      emission.
AB  - Compact Kirkpatrick-Baez microscope mirror components for use in imaging laser
      plasma x-ray emission have been manufactured, coated, and tested. A single mirror
      pair has dimensions of 14 * 7 * 9 mm and a best resolution of ~5 MUm. The mirrors
      are coated with Ir providing a useful energy range of 2-8 keV when operated at a
      grazing angle of 0.7 degrees . The mirrors can be circularly arranged to provide
      16 images of the target emission a configuration best suited for use in
      combination with a custom framing camera [F. J. Marshall, J. A. Oertel, and P. J.
      Walsh, Rev. Sci. Instrum. 75, 4045 (2004)]. An alternative arrangement of the
      mirrors would allow alignment of the images with a four-strip framing camera such
      as described in D. K. Bradley et al. [Rev. Sci. Instrum. 66, 716 (1995)].

PMID- 23127024
TI  - Molybdenum emission from impurity-induced m = 1 snake-modes on the Alcator C-Mod
      tokamak.
AB  - A suite of novel high-resolution spectroscopic imaging diagnostics has
      facilitated the identification and localization of molybdenum impurities as the
      main species during the formation and lifetime of m = 1 impurity-induced snake
      modes on Alcator C-Mod. Such measurements made it possible to infer, for the
      first time, the perturbed radiated power density profiles from which the impurity
      density can be deduced.

PMID- 23127026
TI  - Extracting core shape from x-ray images at the National Ignition Facility.
AB  - Measuring the shape of implosions is critical to inertial confinement fusion
      experiments at the National Ignition Facility. We have developed techniques that
      have proven successful for extracting shape information from images of x-ray self
      emission recorded by a variety of diagnostic instruments for both DT-filled
      targets and low-yield surrogates. These key results help determine optimal laser
      and target parameters leading to ignition. We have compensated for instrumental
      response and have employed a variety of image processing methods to remove
      artifacts from the images while retaining salient features. The implosion shape
      has been characterized by decomposing intensity contours into Fourier and
      Legendre modes for different lines of sight. We also describe procedures we have
      developed for estimating uncertainties in these measurements.

PMID- 23127027
TI  - Concept development for the ITER equatorial port visible/infrared wide angle
      viewing system.
AB  - The ITER equatorial port visible/infrared wide angle viewing system concept is
      developed from the measurement requirements. The proposed solution situates 4
      viewing systems in the equatorial ports 3, 9, 12, and 17 with 4 views each
      (looking at the upper target, the inner divertor, and tangentially left and
      right). This gives sufficient coverage. The spatial resolution of the divertor
      system is 2 times higher than the other views. For compensation of vacuum-vessel
      movements, an optical hinge concept is proposed. Compactness and low neutron
      streaming is achieved by orienting port plug doglegs horizontally. Calibration
      methods, risks, and R&D topics are outlined.

PMID- 23127028
TI  - A monochromatic x-ray imaging system for characterizing low-density foams.
AB  - In high energy density laser experiments, targets often require small, low
      density, foam components. However, their limited size can preclude single
      component characterization, forcing one to rely solely on less accurate bulk
      measurements. We have developed a monochromatic imaging system to characterize
      both the density and uniformity of single component low-mass foams. This x-ray
      assembly is capable of determining line-averaged density variations near the 1%
      level, and provides statistically identical results to those obtained at the
      Brookhaven's NSLS. This system has the added benefit of providing two-dimensional
      density data, allowing an assessment of density uniformity.

PMID- 23127029
TI  - A new aperture for neutron and x-ray imaging of inertial confinement fusion
      experiments.
AB  - Recent  neutron imaging of experiments at the National Ignition Facility has
      provided useful information about the hotspot shape and cold-fuel distribution
      and has also given insight into avenues for improvement. Neutron image
      reconstruction depends on accurate pointing information because the point-spread
      function of the neutron aperture is not shift invariant. Current pointing
      techniques are limited in their accuracy and rely upon detailed information about
      the as-built structure of the array, which is difficult to determine. We present
      a technique for extracting high-precision pointing information from both neutron
      and x-ray images, and a new aperture design with features to facilitate this
      technique, and allow future co-registration of neutron and x-ray images.

PMID- 23127030
TI  - Optical diagnostic suite (schlieren, interferometry, and grid image
      refractometry) on OMEGA EP using a 10-ps, 263-nm probe beam.
AB  - A 10-ps, 263-nm (4omega) laser is being built to probe plasmas produced on the
      OMEGA EP [J. H. Kelly, L. J. Waxer, V. Bagnoud, I. A. Begishev, J. Bromage, B. E.
      Kruschwitz, T. E. Kessler, S. J. Loucks, D. N. Maywar, R. L. McCrory et al., J.
      Phys. IV France 133, 75-80 (2006)]. A suite of optical diagnostics (schlieren,
      interferometry, and grid image refractometry) has been designed to diagnose and
      characterize a wide variety of plasmas. Light scattered by the probe beam is
      collected by an f/4 catadioptric telescope and a transport system is designed to
      image with a near-diffraction-limited resolution (~1 - MUm full width at half
      maximum) over a 5-mm field of view to a diagnostic table. The transport system
      provides a contrast greater than 1 : 10(4) with respect to all wavelengths
      outside of the 263 +/- 2 nm measurement range.

PMID- 23127031
TI  - Fast visible imaging and edge turbulence analysis in QUEST.
AB  - A fast visible imaging system is installed on the spherical tokamak QUEST to
      study edge turbulence. The camera uses a complementary metal-oxide semiconductor
      detector with a maximum resolution of 1024 * 1024 at 7000 frames/s (fps) and can
      achieve 775 kfps at a resolution of 128 * 24. In this paper, we present the
      salient features of the system and its application to study edge turbulence in
      8.2 GHz ECRH driven slab plasma, without plasma current. Vertical magnetic field
      (B(z)) topology is varied with three sets of poloidal field (PF) coils and the
      variation in the edge turbulence is investigated as a function of the B(z)
      strength and curvature. Fluctuation amplitude was highest for the shallow PF
      well. Cross-correlation coefficient shows distinct coherent mode along z
      direction at the steep density gradient region and it grows with the PF mirror
      ratio.

PMID- 23127033
TI  - Novel energy resolving x-ray pinhole camera on Alcator C-Mod.
AB  - A new energy resolving x-ray pinhole camera has been recently installed on
      Alcator C-Mod. This diagnostic is capable of 1D or 2D imaging with a spatial
      resolution of ~1 cm, an energy resolution of ~1 keV in the range of 3.5-15 keV
      and a maximum time resolution of 5 ms. A novel use of a Pilatus 2 hybrid-pixel x
      ray detector [P. Kraft et al., J. Synchrotron Rad. 16, 368 (2009)] is employed in
      which the lower energy threshold of individual pixels is adjusted, allowing
      regions of a single detector to be sensitive to different x-ray energy ranges.
      Development of this new detector calibration technique was done as a
      collaboration between PPPL and Dectris Ltd. The calibration procedure is
      described, and the energy resolution of the detector is characterized. Initial
      data from this installation on Alcator C-Mod is presented. This diagnostic
      provides line-integrated measurements of impurity emission which can be used to
      determine impurity concentrations as well as the electron energy distribution.

PMID- 23127034
TI  - A new scheme for stigmatic x-ray imaging with large magnification.
AB  - This paper describes a new x-ray scheme for stigmatic imaging. The scheme
      consists of one convex spherically bent crystal and one concave spherically bent
      crystal. The radii of curvature and Bragg reflecting lattice planes of the two
      crystals are properly matched to eliminate the astigmatism, so that the
      conditions for stigmatic imaging are met for a particular wavelength. The
      magnification is adjustable and solely a function of the two Bragg angles or
      angles of incidence. Although the choice of Bragg angles is constrained by the
      availability of crystals, this is not a severe limitation for the imaging of
      plasmas, since a particular wavelength can be selected from the bremsstrahlung
      continuum. The working principle of this imaging scheme has been verified with
      visible light. Further tests with x rays are planned for the near future.

PMID- 23127032
TI  - Soft x-ray images of the laser entrance hole of ignition hohlraums.
AB  - Hohlraums are employed at the national ignition facility to convert laser energy
      into a thermal x-radiation drive, which implodes a fusion capsule, thus
      compressing the fuel. The x-radiation drive is measured with a low spectral
      resolution, time-resolved x-ray spectrometer, which views the region around the
      hohlraum's laser entrance hole. This measurement has no spatial resolution. To
      convert this to the drive inside the hohlraum, the size of the hohlraum's opening
      ("clear aperture") and fraction of the measured x-radiation, which comes from
      this opening, must be known. The size of the clear aperture is measured with the
      time integrated static x-ray imager (SXI). A soft x-ray imaging channel has been
      added to the SXI to measure the fraction of x-radiation emitted from inside the
      clear aperture. A multilayer mirror plus filter selects an x-ray band centered at
      870 eV, near the peak of the x-ray spectrum of a 300 eV blackbody. Results from
      this channel and corrections to the x-radiation drive are discussed.

PMID- 23127035
TI  - An evaluation of high energy bremsstrahlung background in point-projection x-ray
      radiography experiments.
AB  - Backlit pinhole x-ray radiography has provided high-resolution images in many
      recent high-energy-density laser experiments. Its aim is to image the object of
      interest with a roughly monochromatic Kalpha source. However, despite the high
      intrinsic brightness achieved by the technique, data on x-ray film have shown a
      signal to background ratio near one, with data on image plates producing a higher
      background. This has been attributed, without direct evidence, to the interaction
      of suprathermal electrons with the (high Z) pinhole substrate. We present here
      the first direct measurement of the hard x-rays produced by such a backlighter
      target and a test of an approach to reducing the background. Specifically, a
      thick, low-Z layer was added on the side of the substrate toward the detector,
      intended to stop the energetic electrons and produce smaller emissions. Results
      from the Omega-60 laser experiment showed that the oft-seen background signal is
      in the range of 60-80 keV, a plausible energy range for energetic electrons
      produced in the laser-irradiated plasma. It also showed a comparable level of
      background signal in both types of targets. The work presented here includes
      target design and motivating theory, as well as the unexpected findings about x
      ray background production.

PMID- 23127036
TI  - Sound velocity measurements by x-ray shadowgraph technique for melting phenomena
      at ultrahigh-pressure regime.
AB  - Developments in measuring sound velocity of matter under ultrahigh pressure are
      described. We employed a time-resolved x-ray shadowgraph technique to measure the
      sound velocity of shock-compressed diamond and iron foils at around melt. The
      sound velocity significantly dropped at melting, a behavior that has been
      difficult to clarify by conventional measurements by subtracting particle
      velocity from shock velocity (u(s) - u(p)). In addition to sound velocity, other
      important parameters were also obtained simultaneously.

PMID- 23127037
TI  - Shell trajectory measurements from direct-drive implosion experiments.
AB  - A technique to measure the shell trajectory in direct-drive inertial confinement
      fusion implosions is presented. The x-ray self emission of the target is measured
      with an x-ray framing camera. Optimized filtering limits the x-ray emission from
      the corona plasma, isolating a sharp intensity gradient very near the ablation
      surface. This enables one to measure the radius of the imploding shell with an
      accuracy better than 1 MUm and to determine a 200-ps average velocity to better
      than 2%.

PMID- 23127038
TI  - Full toroidal imaging of non-axisymmetric plasma material interaction in the
      National Spherical Torus Experiment divertor.
AB  - A pair of two dimensional fast cameras with a wide angle view (allowing a full
      radial and toroidal coverage of the lower divertor) was installed in the National
      Spherical Torus Experiment in order to monitor non-axisymmetric effects. A custom
      polar remapping procedure and an absolute photometric calibration enabled the
      easier visualization and quantitative analysis of non-axisymmetric plasma
      material interaction (e.g., strike point splitting due to application of 3D
      fields and effects of toroidally asymmetric plasma facing components).

PMID- 23127039
TI  - Applications of non-periodic multilayer optics for high-resolution x-ray
      microscopes below 30 keV.
AB  - Multilayer mirrors with enhanced bandwidth were developed with special
      performances for dense plasma diagnostics and mainly for high spatial resolution
      x-ray imaging. The multilayer coatings are designed to provide broadband x-ray
      reflectance at low grazing incidence angles. They are deposited onto toroidal
      mirror substrates. Our research is directed at the development of non-periodic
      (depth graded) W/Si multilayer specifically designed for use in the 1 to 30 keV
      photon energy band. First, we present a study for a 5 to 22 keV x-ray spectral
      window at 0.45 degrees  grazing angle. The goal is to obtain a high and constant
      reflectivity. Second, we have modeled a broadband mirror coating for harder x
      rays in the range from 10 to 30 keV, with a non-periodic structure containing 300
      W/SiC layers with periods in the range from 0.8 to 4 nm, designed for 0.35
      degrees  grazing incidence angle.

PMID- 23127040
TI  - Concept to diagnose mix with imaging x-ray Thomson scattering.
AB  - Turbulent mixing of two fluid species is a ubiquitous problem, prevalent in
      systems such as inertial confinement fusion (ICF) capsule implosions, supernova
      remnants, and other astrophysical systems. In complex, high Reynolds number
      compressible high energy density (HED) flows such as these, hydrodynamic
      instabilities initiate the turbulent mixing process, which can then feedback and
      alter the mean hydrodynamic motion through nonlinear processes. In order to
      predict how these systems evolve under turbulent conditions, models are used.
      However, these models require detailed quantitative data to validate and
      constrain their detailed physics models as well as improve them. Providing this
      much needed data is currently at the forefront of HED research but is proving
      elusive due to a lack of available diagnostics capable of directly measuring
      detailed flow variables. Thomson scattering is a promising technique in this
      regard as it provides fundamental conditions of the flow (rho, T, Zbar) due to
      its direct interaction with the small scales of the fluid or plasma and was
      recently considered as a possible mix diagnostic. With the development of imaging
      x-ray Thomson scattering (IXRTS) obtaining spatial profiles of these variables is
      within reach. We propose a novel use of the IXRTS technique that will provide
      more detailed quantitative data required for model validation in mix experiments.

PMID- 23127041
TI  - Multi-energy x-ray imaging and sensing for diagnostic and control of the burning
      plasma.
AB  - New diagnostic and sensor designs are needed for future burning plasma (BP)
      fusion experiments, having good space and time resolution and capable of
      prolonged operation in the harsh BP environment. We evaluate the potential of
      multi-energy x-ray imaging with filtered detector arrays for BP diagnostic and
      control. Experimental studies show that this simple and robust technique enables
      measuring with good accuracy, speed, and spatial resolution the T(e) profile,
      impurity content, and MHD activity in a tokamak. Applied to the BP this
      diagnostic could also serve for non-magnetic sensing of the plasma position,
      centroid, ELM, and RWM instability. BP compatible x-ray sensors are proposed
      using "optical array" or "bi-cell" detectors.

PMID- 23127047
TI  - Point/counterpoint: it is not appropriate to "deform" dose along with deformable
      image registration in adaptive radiotherapy.

PMID- 23127048
TI  - The cerebral vasomotor response in varying CO(2) concentrations, as evaluated
      using cine phase contrast MRI: Flow, volume, and cerebrovascular resistance
      indices.
AB  - PURPOSE: Previous studies have identified that impaired cerebral vasomotor
      reactivity (VMR) is associated with a higher risk of stroke and transient
      ischemic attack. This study aims to evaluate VMR by measuring the blood flow
      waveforms of the supplying arteries and dural sinuses using cine phase contrast
      MRI (PC MRI) and hypercapnic challenge. METHODS: PC MRI flow quantification was
      performed on an oblique slice approximately perpendicular to the target vessels
      to include the left (LICA) and right internal carotid artery (RICA), basilar
      artery (BA), sinus rectus (SR), and superior sagittal sinus (SSS). A total of
      four PC MRI scans were performed at different CO(2) concentrations (room air and
      3%, 5%, and 7% CO(2)). RESULTS: The analyses obtained the flow parameters and
      cerebrovascular resistance parameters for all five vessels. Results indicated
      that the vascular resistance indices decreased with increasing CO(2)
      concentration in four vessels (LICA, RICA, BA, and SR). The obtained VMR
      parameters demonstrated exponential increases with increasing CO(2)
      concentration. CONCLUSIONS: Using entire blood flow waveforms, this study applied
      separate flow dynamics during systolic and diastolic periods to obtain
      cerebrovascular resistance parameters and extensive flow-related information. It
      is the first to investigate the cerebrovascular resistance parameters under
      hypercapnic challenge using cine MRI. This technique could provide a useful tool
      for clinical application in cerebrovascular disease.

PMID- 23127049
TI  - Image registration using radial basis functions with adaptive radius.
AB  - PURPOSE: Deformable registration of medical images often requires initial rigid
      alignment. Because of variations in the articulation of bony structures, rigid
      alignment can capture only limited regions of the image. We propose a method that
      allows us to compensate for misalignment of mobile parts, which leads to improved
      accuracy of deformable registration. The method is based on matching landmarks
      using radial basis functions (RBF) with adaptive radius. METHODS: Based on the
      assumption that the compactly positioned landmarks likely delineate an anatomic
      structure whose position needs to be corrected, the algorithm incorporates
      unsupervised clustering of landmarks based on their positions within the
      reference image. It calculates an appropriate RBF radius based on the set of
      pairwise distances between landmarks within the cluster. The algorithm
      distinguishes between clusters of different size and between clusters of
      spherical and elongated shape, and assigns the optimal RBF radius for each
      cluster in order to restrict the deformation field to the closest vicinity of the
      structure of interest. RESULTS: Experiments with synthetic images demonstrate
      sensitivity of registration results to the choice of the radius of RBF support.
      We have statistically validated the methods on a large set of pulmonary
      landmarks. We also tested the method on medical use cases that show that it is
      potentially advantageous for initial registration of images with large spatial
      dislocations. CONCLUSIONS: The results of registration of CT images demonstrate
      that an automated selection of the RBF radius simplifies the registration routine
      and improves the registration quality. The selection is based on two criteria of
      preserving diffeomorphism of deformation and localization of the deformation
      within a desired area of the image.

PMID- 23127050
TI  - Effects of protocol and obesity on dose conversion factors in adult body CT.
AB  - PURPOSE: In computed tomography (CT), organ dose, effective dose, and risk index
      can be estimated from volume-weighted CT dose index (CTDI(vol)) or dose-length
      product (DLP) using conversion coefficients. Studies have investigated how these
      coefficients vary across scanner models, scan parameters, and patient size.
      However, their variability across CT protocols has not been systematically
      studied. Furthermore, earlier studies of the effect of patient size have not
      included obese individuals, which currently represent more than one-third of U.S.
      adults. The purpose of this study was to assess the effects of protocol and
      obesity on dose and risk conversion coefficients in adult body CT. METHODS: Whole
      body computational phantoms were created from clinical CT images of six adult
      patients (three males, three females), representing normal-weight patients and
      patients of three obesity classes. Body CT protocols at our institution were
      selected and categorized into ten examination categories based on anatomical
      region examined. A validated Monte Carlo program was used to estimate organ dose.
      Organ dose estimates were normalized by CTDI(vol) and size-specific dose estimate
      (SSDE) to obtain organ dose conversion coefficients (denoted as h and h(ss)
      factors, respectively). Assuming each phantom to be 20, 40, and 60 years old,
      effective dose and risk index were calculated and normalized by DLP to obtain
      effective dose and risk index conversion coefficients (denoted as k and q
      factors, respectively). Coefficient of variation was used to quantify the
      variability of each conversion coefficient across examination categories. The
      effect of obesity was assessed by comparing each obese phantom with the normal
      weight phantom of the same gender. RESULTS: For a given organ, the variability of
      h factor across examination categories that encompassed the entire organ volume
      was generally within 15%. However, k factor varied more across examination
      categories (15%-27%). For all three ages, the variability of q factor was small
      for male (<10%), but large for female phantoms (21%-43%). Relative to the normal
      weight phantoms, the reduction in h factor (an average across fully encompassed
      organs) was 17%-42%, 17%-40%, and 51%-63% for obese-class-I, obese-class-II, and
      obese-class-III phantoms, respectively. h(ss) factor was not independent of
      patient diameter and generally decreased with increasing obesity. Relative to the
      normal-weight phantoms, the reduction in k factor was 12%-40%, 14%-46%, and 44%
      59% for obese-class-I, obese-class-II, and obese-class-III phantoms,
      respectively. The respective reduction in q factor was 11%-36%, 17%-42%, and 48%
      59% at 20 years of age and similar at other ages. CONCLUSIONS: In adult body CT,
      dose to an organ fully encompassed by the primary radiation beam can be estimated
      from CTDI(vol) using a protocol-independent conversion coefficient. However,
      fully encompassed organs only account for 50% +/- 19% of k factor and 46% +/- 24%
      of q factor. Dose received by partially encompassed organs is also substantial.
      To estimate effective dose and risk index from DLP, it is necessary to use
      conversion coefficients specific to the anatomical region examined. Obesity has a
      significant effect on dose and risk conversion coefficients, which cannot be
      predicted using body diameter alone. SSDE-normalized organ dose is not
      independent of diameter. SSDE itself generally overestimates organ dose for obese
      patients.

PMID- 23127051
TI  - Optimization of K-edge imaging with spectral CT.
AB  - PURPOSE: Spectral/multienergy CT has the potential to distinguish different
      materials by K-edge characteristics. K-edge imaging involves the two energy bins
      on both sides of a K-edge. The authors propose a K-edge imaging optimization
      model to determine these two energy bins. METHODS: K-edge image contrast with
      spectral CT depends on the specifications of the two energy bins on both sides of
      a K-edge in the attenuation profile of a relatively high atomic number material.
      The wider the energy bin width is, the lower the noise level is, and the poorer
      the reconstructed image contrast is. Here the authors introduce the signal
      difference to noise ratio (SDNR) criterion to optimize the energy bin widths on
      both sides of the K-edge for the maximum SDNR. RESULTS: The authors study K-edge
      imaging with spectral CT, analyze the effect of K-edge energy bins on the
      resultant image quality, and establish guidelines for the optimization of energy
      thresholds. In simulation, the authors demonstrate that our K-edge imaging
      optimization approach maximizes SDNR in reconstructed images. CONCLUSIONS: This
      proposed approach can be readily generalized to deal with more general settings
      and determine the best energy bins for K-edge imaging.

PMID- 23127052
TI  - Technical note: precision and accuracy of a commercially available CT optically
      stimulated luminescent dosimetry system for the measurement of CT dose index.
AB  - PURPOSE: To determine the precision and accuracy of CTDI(100) measurements made
      using commercially available optically stimulated luminescent (OSL) dosimeters
      (Landaur, Inc.) as beam width, tube potential, and attenuating material were
      varied. METHODS: One hundred forty OSL dosimeters were individually exposed to a
      single axial CT scan, either in air, a 16-cm (head), or 32-cm (body) CTDI phantom
      at both center and peripheral positions. Scans were performed using nominal total
      beam widths of 3.6, 6, 19.2, and 28.8 mm at 120 kV and 28.8 mm at 80 kV. Five
      measurements were made for each of 28 parameter combinations. Measurements were
      made under the same conditions using a 100-mm long CTDI ion chamber. Exposed OSL
      dosimeters were returned to the manufacturer, who reported dose to air (in mGy)
      as a function of distance along the probe, integrated dose, and CTDI(100).
      RESULTS: The mean precision averaged over 28 datasets containing five
      measurements each was 1.4% +/- 0.6%, range = 0.6%-2.7% for OSL and 0.08% +/-
      0.06%, range = 0.02%-0.3% for ion chamber. The root mean square (RMS) percent
      differences between OSL and ion chamber CTDI(100) values were 13.8%, 6.4%, and
      8.7% for in-air, head, and body measurements, respectively, with an overall RMS
      percent difference of 10.1%. OSL underestimated CTDI(100) relative to the ion
      chamber 21/28 times (75%). After manual correction of the 80 kV measurements, the
      RMS percent differences between OSL and ion chamber measurements were 9.9% and
      10.0% for 80 and 120 kV, respectively. CONCLUSIONS: Measurements of CTDI(100)
      with commercially available CT OSL dosimeters had a percent standard deviation of
      1.4%. After energy-dependent correction factors were applied, the RMS percent
      difference in the measured CTDI(100) values was about 10%, with a tendency of OSL
      to underestimate CTDI relative to the ion chamber. Unlike ion chamber methods,
      however, OSL dosimeters allow measurement of the radiation dose profile.

PMID- 23127053
TI  - Unfolding linac photon spectra and incident electron energies from experimental
      transmission data, with direct independent validation.
AB  - PURPOSE: In a recent computational study, an improved physics-based approach was
      proposed for unfolding linac photon spectra and incident electron energies from
      transmission data. In this approach, energy differentiation is improved by
      simultaneously using transmission data for multiple attenuators and detectors,
      and the unfolding robustness is improved by using a four-parameter functional
      form to describe the photon spectrum. The purpose of the current study is to
      validate this approach experimentally, and to demonstrate its application on a
      typical clinical linac. METHODS: The validation makes use of the recent
      transmission measurements performed on the Vickers research linac of National
      Research Council Canada. For this linac, the photon spectra were previously
      measured using a NaI detector, and the incident electron parameters are
      independently known. The transmission data are for eight beams in the range 10-30
      MV using thick Be, Al and Pb bremsstrahlung targets. To demonstrate the approach
      on a typical clinical linac, new measurements are performed on an Elekta Precise
      linac for 6, 10 and 25 MV beams. The different experimental setups are modeled
      using EGSnrc, with the newly added photonuclear attenuation included. RESULTS:
      For the validation on the research linac, the 95% confidence bounds of the
      unfolded spectra fall within the noise of the NaI data. The unfolded spectra
      agree with the EGSnrc spectra (calculated using independently known electron
      parameters) with RMS energy fluence deviations of 4.5%. The accuracy of unfolding
      the incident electron energy is shown to be ~3%. A transmission cutoff of only
      10% is suitable for accurate unfolding, provided that the other components of the
      proposed approach are implemented. For the demonstration on a clinical linac, the
      unfolded incident electron energies and their 68% confidence bounds for the 6, 10
      and 25 MV beams are 6.1 +/- 0.1, 9.3 +/- 0.1, and 19.3 +/- 0.2 MeV, respectively.
      The unfolded spectra for the clinical linac agree with the EGSnrc spectra
      (calculated using the unfolded electron energies) with RMS energy fluence
      deviations of 3.7%. The corresponding measured and EGSnrc-calculated transmission
      data agree within 1.5%, where the typical transmission measurement uncertainty on
      the clinical linac is 0.4% (not including the uncertainties on the incident
      electron parameters). CONCLUSIONS: The approach proposed in an earlier study for
      unfolding photon spectra and incident electron energies from transmission data is
      accurate and practical for clinical use.

PMID- 23127054
TI  - 2D lag and signal nonlinearity correction in an amorphous silicon EPID and their
      impact on pretreatment dosimetric verification.
AB  - PURPOSE: This investigation provides measurements of signal lag and nonlinearity
      separately for the Varian aS500 electronic portal imaging device (EPID), and an
      algorithm to correct for these effects in 2D; their potential impact on intensity
      modulated radiation therapy (IMRT) verification is also investigated. The authors
      quantify lag, as a function of both delivered monitor units (MU) and time, by
      using a range of MUs delivered at a clinically used rate of 400 MU/min. Explicit
      cumulative lag curves are thus determined for a range of MUs and times between
      the end of irradiation and the end of image acquisition. Signal nonlinearity is
      also investigated as a function of total MUs delivered. The family of cumulative
      lag curves and signal nonlinearity are then used to determine their effects on
      dynamic multileaf collimator (MLC) (IMRT) deliveries, and to correct for theses
      effects in 2D. METHODS: Images acquired with an aS500 EPID and Varis Portal
      Vision software were used to quantify detector lag and signal-nonlinearity. For
      the signal lag investigation, Portal-Vision's service monitor was used to acquire
      EPID images at a rate of 8 frames/s. The images were acquired during irradiation
      and 66 s thereafter, by inhibiting the M-holdoff-In signal of the Linac for a
      range of 4.5-198.5 MUs. Relative cumulative lag was calculated by integrating the
      EPID signal for a time after beam-off, and normalizing this to the integrated
      EPID signal accumulated during radiation. Signal nonlinearity was studied by
      acquiring 10 * 10 cm(2) open-field EPID images in "integrated image" mode for a
      range of 2-500 MUs, and normalized to the 100 MU case. All data were incorporated
      into in-house written software to create a 2D correction map for these effects,
      using the field's MLC file and a field-specific calculated 2D "time-map," which
      keeps track of the time elapsed from the last fluence delivered at each given
      point in the image to the end of the beam delivery. RESULTS: Relative cumulative
      lag curves reveal that the lag alone can deviate the EPID's perceived dose by as
      large as 6% (1 MU delivery, 60 s postirradiation). For signal nonlinearity
      relative to 100 MU, EPID signals per MU of 0.84 and 1.01 were observed for 2 and
      500 MUs, respectively. Correction maps were applied to a 1 cm sweeping-window 14
      * 14 cm(2) field and clinical head-and-neck IMRT field. A mean correction of
      1.028 was implemented in the head-and-neck field, which significantly reduced lag
      related asymmetries in the EPID images, and restored linearity to the EPID
      imager's dose response. Corrections made to the sweeping-field showed good
      agreement with the treatment planning system-predicted field, yielding an average
      percent difference of 0.05% +/- 0.91%, compared to the -1.32% +/- 1.02% before
      corrections, or 1.75% +/- 1.04% when only a signal nonlinearity correction is
      made. CONCLUSIONS: Lag and signal-nonlinearity have been quantified for an aS500
      EPID imager, and an effective 2D correction method has been developed which
      effectively removes nonlinearity and lag effects. Both of these effects were
      shown to negatively impact IMRT verifications. Especially fields that involve
      prolonged irradiation and small overall MUs should be corrected for in 2D.

PMID- 23127055
TI  - Single-scan rest/stress imaging (18)F-labeled flow tracers.
AB  - PURPOSE: The authors report a novel measurement strategy to obtain both rest and
      stress blood flow during a single, relatively short, scan session. METHODS:
      Measurement of rest-stress myocardial blood flow with long-lived tracers usually
      requires separate scan sessions to remove the confounding effects of residual
      radioactivity concentration in the blood and tissue. The innovation of this
      method is to treat the rest-stress scan as a single entity in which the flow
      parameters change due to pharmacological challenge. With this approach the fate
      of a tracer molecule is naturally accounted for, no matter if it was introduced
      during the rest or stress phase of the study. Two new dual-injection kinetic
      models are considered that represent the response to pharmacological stress as a
      transitional or transient increase of myocardial blood flow. The authors present
      the theory of the method followed by the specific application of the theory to
      (18)F-Flurpiridaz, a new myocardial flow-imaging agent. RESULTS: Myocardial blood
      flow was accurately and precisely estimated from a single-scan rest/stress study
      for the long half-lived tracer (18)F-Flurpiridaz. By accounting for the time
      dependence of the kinetic parameters, the proposed models achieved good accuracy
      and precision (5%) under different vasodilators and different ischemic states.
      CONCLUSIONS: Detailed simulations predict that accurate and precise rest-stress
      blood flow measurements can be obtained in 20-30 min.

PMID- 23127056
TI  - Dosimetric investigation of accelerated partial breast irradiation (APBI) using
      CyberKnife.
AB  - PURPOSE: To investigate the dosimetric feasibility of accelerated partial breast
      irradiation (APBI) using CyberKnife. METHODS: Fourteen previously treated
      patients with early-stage breast cancer were selected for a retrospective study.
      Six of these patients had been treated to 38.5 Gy in 10 fractions in a phase III
      accelerated partial breast trial and the rest of the patients were treated to
      50.4 Gy in 28 fractions. In this planning study, the guidelines in the protocol
      for the phase III partial breast trial were followed for organ delineation and
      CyberKnife planning. The achievable dosimetric parameters from all CyberKnife
      plans were compared to Intensity-modulated radiation therapy (IMRT) and 3D-CRT
      methods. The reproducibility of the dose delivery with and without respiratory
      motion was assessed through delivering a patient plan to a breast phantom.
      Different dose calculation algorithms were also compared between ray tracing and
      Monte Carlo. RESULTS: For all the patients in the study, the dosimetric
      parameters met the guidelines from the NSABP B39/RTOG 0413 protocol strictly. The
      mean PTV volume covered by 100% of the prescription dose was 95.7 +/- 0.7% (94.7%
      97.1%). The mean maximal dose was 104 +/- 2% of the prescription dose. The mean
      V(50%) and mean V(100%) to the ipsilateral normal breast were 23.1 +/- 11.6% and
      9.0 +/- 5.8%, respectively. The conformity index of all plans was 1.14 +/- 0.04.
      The maximum dose to the contralateral breast varied from 1.3 cGy to 111 cGy. The
      mean V(5%) and mean V(30%) to the contralateral and ipsilateral lungs were 1.0 +/
      1.6% and 1.3 +/- 1.2%, respectively. In our study, the mean V(5%) to the heart
      was 0.2 +/- 0.5% for right-sided tumors and 9.4 +/- 10.1% for left-sided tumors.
      Compared with IMRT and 3D-CRT planning, the PTV coverage from CyberKnife planning
      was the highest, and the ratio of V(20%) to V(100%) of the breast from CyberKnife
      planning was the smallest. The heart and lung doses were similar in all the
      techniques except that the V(5%) for the lung and heart in CyberKnife planning
      was slightly higher. CONCLUSIONS: The dosimetric feasibility of APBI using
      CyberKnife was investigated in this retrospective study. All the dosimetric
      parameters strictly met the guidelines from the NSABP B39/RTOG 0413 protocol.
      With advanced real-time tracking capability, CyberKnife should provide better
      target coverage and spare nearby critical organs for APBI treatment.

PMID- 23127057
TI  - Dosimetric effect of intrafraction tumor motion in phase gated lung stereotactic
      body radiotherapy.
AB  - PURPOSE: A major concern for lung intensity modulated radiation therapy delivery
      is the deviation of actually delivered dose distribution from the planned one due
      to simultaneous movements of multileaf collimator (MLC) leaves and tumor. For
      gated lung stereotactic body radiotherapy treatment (SBRT), the situation becomes
      even more complicated because of SBRT's characteristics such as fewer fractions,
      smaller target volume, higher dose rate, and extended fractional treatment time.
      The purpose of this work is to investigate the dosimetric effect of intrafraction
      tumor motion during gated lung SBRT delivery by reconstructing the delivered dose
      distribution with real-time tumor motion considered. METHODS: The tumor motion
      data were retrieved from six lung patients. Each of them received three fractions
      of stereotactic radiotherapy treatments with Cyberknife Synchrony (Accuray,
      Sunnyvale, CA). Phase gating through an external surrogate was simulated with a
      gating window of 5 mm. The resulting residual tumor motion curves during gating
      (beam-on) were retrieved. Planning target volume (PTV) was defined as physician
      contoured clinical target volume (CTV) surrounded by an isotropic 5 mm margin.
      Each patient was prescribed with 60 Gy/3 fractions. The authors developed an
      algorithm to reconstruct the delivered dose with tumor motion. The DMLC segments,
      mainly leaf position and segment weighting factor, were recalculated according to
      the probability density function of tumor motion curve. The new DMLC sequence
      file was imported back to treatment planning system to reconstruct the dose
      distribution. RESULTS: Half of the patients in the study group experienced PTV
      D95% deviation up to 26% for fractional dose and 14% for total dose. CTV mean
      dose dropped by 1% with tumor motion. Although CTV is almost covered by
      prescribed dose with 5 mm margin, qualitative comparison on the dose
      distributions reveals that CTV is on the verge of underdose. The discrepancy
      happens due to tumor excursion outside of the gating window, which, for our study
      group, is mainly caused by baseline shift, i.e., the change in general trend of
      the motion curve during extended period of treatment time. CONCLUSIONS: The dose
      deviation in PTV and CTV due to target motion is not always negligible in gated
      SBRT. Although CTVs are covered sufficiently with prescribed dose in most cases,
      some are on the verge of underdose due to large tumor excursion caused by factors
      such as baseline shift.

PMID- 23127058
TI  - Monte Carlo performance on the x-ray converter thickness in digital mammography
      using software breast models.
AB  - PURPOSE: In x-ray mammography, some of the components that play significant role
      to early diagnosis are the x-ray source, the breast composition as well as the
      composition of the x-ray converter. Various studies have previously investigated
      separately the influence of breast characteristics and detector configuration on
      the optimization of mammographic imaging systems. However, it is important to
      examine the combined effect of both components in improving the signal transfer
      properties in mammography systems of the mammograms. In the present study, the
      authors compared and evaluated x-ray converters using software breast models and
      realistic mammographic spectra in terms of: (a) zero-frequency detective quantum
      efficiency (DQE) and (b) sensitivity. The impact of x-ray converter thickness on
      contrast threshold (C(TH)) for observer assessment, based on the Rose model, was
      demonstrated as well. METHODS: Monte Carlo techniques were applied to simulate
      the x-ray interactions within the software breast phantoms and thereafter within
      the detective medium. Simulations involved: (a) two mammographic x-ray spectra:
      28 kV Mo, 0.030 mm Mo, and 32 kV W, 0.050 mm Rh of different entrance surface air
      kerma (ESAK: 3-7 mGy), (b) realistic breast models (dense and fatty) and (c) x
      ray converter materials most frequently considered in investigations on energy
      integrating digital mammography detectors: the Gd(2)O(2)S:Tb granular phosphor,
      the CsI:Tl structured phosphor, and the a-Se photoconductive layer. Detector
      material thickness was considered to vary in the range from 50 mg/cm(2) up to 150
      mg/cm(2). RESULTS: The Monte Carlo study showed that: (a) the x-ray beam becomes
      less penetrating after passing through dense breasts leading to higher values of
      zero-frequency DQE of the x-ray imaging converters and improved C(TH) values in
      all cases considered, (b) W/Rh target/filter combination results in improved
      C(TH) values at higher ESAK values, and (c) a-Se shows higher zero-frequency DQE
      values than the phosphor-based converters, Gd(2)O(2)S:Tb and CsI:Tl. However,
      thicker layers of CsI:Tl could be comparable to a-Se layers achieving
      approximately 27.6% C(TH) improvement at a thickness of 150 mg/cm(2).
      CONCLUSIONS: The present Monte Carlo investigation indicates that in the energy
      range employed in mammography, an upper limit, approximately 100 mg/cm(2), should
      be considered in the development of thicker a-Se converters. On the other hand,
      above this thickness value, CsI:Tl converter could improve its imaging
      performance.

PMID- 23127059
TI  - In vitro evaluation of the imaging accuracy of C-arm conebeam CT in cerebral
      perfusion imaging.
AB  - PURPOSE: The authors have developed a method to enable cerebral perfusion CT
      imaging using C-arm based conebeam CT (CBCT). This allows intraprocedural
      monitoring of brain perfusion during treatment of stroke. Briefly, the technique
      consists of acquiring multiple scans (each scan comprised of six sweeps) acquired
      at different time delays with respect to the start of the x-ray contrast agent
      injection. The projections are then reconstructed into angular blocks and
      interpolated at desired time points. The authors have previously demonstrated its
      feasibility in vivo using an animal model. In this paper, the authors describe an
      in vitro technique to evaluate the accuracy of their method for measuring the
      relevant temporal signals. METHODS: The authors' evaluation method is based on
      the concept that any temporal signal can be represented by a Fourier series of
      weighted sinusoids. A sinusoidal phantom was developed by varying the
      concentration of iodine as successive steps of a sine wave. Each step
      corresponding to a different dilution of iodine contrast solution contained in
      partitions along a cylinder. By translating the phantom along the axis at
      different velocities, sinusoidal signals at different frequencies were generated.
      Using their image acquisition and reconstruction algorithm, these sinusoidal
      signals were imaged with a C-arm system and the 3D volumes were reconstructed.
      The average value in a slice was plotted as a function of time. The phantom was
      also imaged using a clinical CT system with 0.5 s rotation. C-arm CBCT results
      using 6, 3, 2, and 1 scan sequences were compared to those obtained using CT.
      Data were compared for linear velocities of the phantom ranging from 0.6 to 1
      cm/s. This covers the temporal frequencies up to 0.16 Hz corresponding to a
      frequency range within which 99% of the spectral energy for all temporal signals
      in cerebral perfusion imaging is contained. RESULTS: The errors in measurement of
      temporal frequencies are mostly below 2% for all multiscan sequences. For single
      scan sequences, the errors increase sharply beyond 0.10 Hz. The amplitude errors
      increase with frequency and with decrease in the number of scans used.
      CONCLUSIONS: Our multiscan perfusion CT approach allows low errors in signal
      frequency measurement. Increasing the number of scans reduces the amplitude
      errors. A two-scan sequence appears to offer the best compromise between accuracy
      and the associated total x-ray and iodine dose.

PMID- 23127060
TI  - Development of a flexible optical fiber based high resolution integrated PET/MRI
      system.
AB  - PURPOSE: The simultaneous measurement of PET and magnetic resonance imaging (MRI)
      is an emerging field for molecular imaging research. Although optical fiber based
      PET/MRI systems have advantages on less interference between PET and MRI, there
      is a drawback in reducing the scintillation light due to the fiber. To reduce the
      problem, the authors newly developed flexible optical fiber bundle based block
      detectors and employed them for a high resolution integrated PET/MRI system.
      METHODS: The flexible optical fiber bundle used 0.5 mm diameter, 80 cm long
      double clad fibers which have dual 12 mm * 24 mm rectangular inputs and a single
      24 mm * 24 mm rectangular output. In the input surface, LGSO scintillators of
      0.025 mol.% (decay time: ~31 ns: 0.9 mm * 1.3 mm * 5 mm) and 0.75 mol.% (decay
      time: ~46 ns: 0.9 mm * 1.3 mm * 6 mm) were optically coupled in depth direction
      to form depth-of-interaction detector, arranged in 11 * 13 matrix and optically
      coupled to the fiber bundle. The two inputs of the bundle are bent for 90 degrees
      , bound to one, and are optically coupled to a Hamamatsu 1-in. square position
      sensitive photomultiplier tube. RESULTS: Light loss due to the fiber bundle could
      be reduced and the performance of the block detectors was improved. Eight optical
      fiber based block detectors (16 LGSO blocks) were arranged in a 56 mm diameter
      ring to form a PET system. Spatial resolution and sensitivity were 1.2 mm full
      width at half-maximum and 1.2% at the central field-of-view, respectively.
      Sensitivity change was less than 1% for 2  degrees C temperature changes. This
      PET system was integrated with a 0.3 T permanent magnet MRI system which has 17
      cm diameter hole at the yoke area for insertion of the PET detector ring. There
      was no observable interference between PET and MRI. Simultaneous imaging of PET
      and MRI was successfully performed for small animal studies. CONCLUSIONS: The
      authors confirmed that the developed high resolution PET/MRI system is promising
      for molecular imaging research.

PMID- 23127061
TI  - Dosimetric measurements of Onyx embolization material for stereotactic
      radiosurgery.
AB  - PURPOSE: Arteriovenous malformations are often treated with a combination of
      embolization and stereotactic radiosurgery. Concern has been expressed in the
      past regarding the dosimetric properties of materials used in embolization and
      the effects that the introduction of these materials into the brain may have on
      the quality of the radiosurgery plan. To quantify these effects, the authors have
      taken large volumes of Onyx 34 and Onyx 18 (ethylene-vinyl alcohol copolymer
      doped with tantalum) and measured the attenuation and interface effects of these
      embolization materials. METHODS: The manufacturer provided large cured volumes
      (~28 cc) of both Onyx materials. These samples were 8.5 cm in diameter with a
      nominal thickness of 5 mm. The samples were placed on a block tray above a stack
      of solid water with an Attix chamber at a depth of 5 cm within the stack. The
      Attix chamber was used to measure the attenuation. These measurements were made
      for both 6 and 16 MV beams. Placing the sample directly on the solid water stack
      and varying the thickness of solid water between the sample and the Attix chamber
      measured the interface effects. The computed tomography (CT) numbers for bulk
      material were measured in a phantom using a wide bore CT scanner. RESULTS: The
      transmission through the Onyx materials relative to solid water was approximately
      98% and 97% for 16 and 6 MV beams, respectively. The interface effect shows an
      enhancement of approximately 2% and 1% downstream for 16 and 6 MV beams. CT
      numbers of approximately 2600-3000 were measured for both materials, which
      corresponded to an apparent relative electron density (RED) rho(e) (w) to water
      of approximately 2.7-2.9 if calculated from the commissioning data of the CT
      scanner. CONCLUSIONS: We performed direct measurements of attenuation and
      interface effects of Onyx 34 and Onyx 18 embolization materials with large
      samples. The introduction of embolization materials affects the dose distribution
      of a MV therapeutic beam, but should be of negligible consequence for effective
      thicknesses of less than 8 mm. The measured interface effects are also small,
      particularly at 6 MV. Large areas of high-density artifacts and low-density
      artifacts can cause errors in dose calculations and need to be identified and
      resolved during planning.

PMID- 23127062
TI  - A Monte Carlo based formalism to identify potential locations at high risk of
      tumor recurrence with a numerical model for glioblastoma multiforme.
AB  - PURPOSE: The strategy currently used to treat glioblastoma multiforme (GBM)
      patients, which mostly relies on population-based failure patterns, does not
      consider the important variability in such patterns reported in the literature.
      As part of the multidisciplinary efforts being made to develop personalized
      therapeutic approaches, numerical models of tumor growth and treatment are
      increasingly being used by different groups around the world. In this study, a
      new formalism relying on the proliferation-invasion model is developed to
      identify potential locations of GBM recurrences. The authors assess the
      sensitivity of the location of potential tumor recurrences to the input parameter
      values predicted for a given patient by varying those values using a Monte-Carlo
      based approach. Our approach is designed to be prospective in the sense that it
      relies on patient-specific imaging data that can be gathered in one single
      preradiotherapy imaging session. METHODS: The authors modeled the infiltration
      paths of glial cells using patient-specific diffusion tensor imaging (DTI) data.
      Nine GBM patients with preradiotherapy DTI data are considered in this study. The
      possible locations of tumor recurrences are determined by randomly selecting many
      ensembles of values for each of the growth and radiobiological parameters in the
      GBM growth model. A novel concept, the occurrence probability (OP), is introduced
      to assess the sensitivity of potential tumor recurrence locations to the input
      parameter values. For a given patient, the OP map is derived from a superposition
      of all potential tumor recurrence locations obtained with all sets of parameter
      values. RESULTS: For eight out of nine of patients, the authors have identified a
      statistically significant region where the OP is above 50%. For two patients,
      these high risk regions are found to be located at a distance greater than 3.9 cm
      from the border of the gross tumor volume highlighting the inaccuracy of current
      margins for some patients. The exact location and size of these volumes with OP >
      50 % are, however, sensitive to the number N of ensembles of parameter values for
      N ? 400. On the other hand, the authors have identified for each patient a
      threshold OP, the OP(T), which defines a volume that converges more rapidly with
      increasing N. The OP(T) for each patient varies between 20% and 40%. The volume
      defined by OP > OP(T) may be an adequate candidate to define a personalized
      margin for radiotherapy treatment planning of GBM patients. CONCLUSIONS: A new
      Monte-Carlo based formalism was described and used to assess the variability of
      sites of potential recurrence predicted by the proliferation-invasion model to
      input parameter values. The authors have shown that high risk areas could be
      consistently identified with a limited number of sets (N ? 400) of randomly
      chosen parameter values. A major strength of this formalism is its potential
      prospective nature. Although a validation of the accuracy of the model-predicted
      tumor recurrence location still remains to be done, our method is potentially
      applicable to orient patient-specific definition of margins.

PMID- 23127064
TI  - MRI simulation for radiotherapy treatment planning.
AB  - Over the last two decades, the computed tomography simulator became the standard
      of the contemporary radiotherapy treatment planning (RTP) process. Along the same
      time, the superb soft tissue contrast of magnetic resonance imaging (MRI) was
      widely incorporated into RTP through the process of image coregistration. This
      review summarizes the efforts of incorporation of MRI data into target definition
      process for RTP based on gained clinical evidence so far and opens a question
      whether the time is up for bringing a MRI-simulator as an additional standard
      imaging tool into radiation oncology departments.

PMID- 23127063
TI  - Visualizing ex vivo radiofrequency and microwave ablation zones using electrode
      vibration elastography.
AB  - PURPOSE: Electrode vibration elastography is a new shear wave imaging technique
      that can be used to visualize thermal ablation zones. Prior work has shown the
      ability of electrode vibration elastography to delineate radiofrequency
      ablations; however, there has been no previous study of delineation of microwave
      ablations or radiological-pathological correlations using multiple observers.
      METHODS: Radiofrequency and microwave ablations were formed in ex vivo bovine
      liver tissue. Their visualization was compared on shear wave velocity and maximum
      displacement images. Ablation dimensions were compared to gross pathology.
      Elastographic imaging and gross pathology overlap and interobserver variability
      were quantified using similarity measures. RESULTS: Elastographic imaging
      correlated with gross pathology. Correlation of area estimates was better in
      radiofrequency than in microwave ablations, with Pearson coefficients of 0.79 and
      0.54 on shear wave velocity images and 0.90 and 0.70 on maximum displacement
      images for radiofrequency and microwave ablations, respectively. The absolute
      relative difference in area between elastographic imaging and gross pathology was
      18.9% and 22.9% on shear wave velocity images and 16.0% and 23.1% on maximum
      displacement images for radiofrequency and microwave ablations, respectively.
      CONCLUSIONS: Statistically significant radiological-pathological correlation was
      observed in this study, but correlation coefficients were lower than other
      modulus imaging techniques, most notably in microwave ablations. Observers
      provided similar delineations for most thermal ablations. These results suggest
      that electrode vibration elastography is capable of imaging thermal ablations,
      but refinement of the technique may be necessary before it can be used to monitor
      thermal ablation procedures clinically.

PMID- 23127065
TI  - Multicriteria optimization for volumetric-modulated arc therapy by decomposition
      into a fluence-based relaxation and a segment weight-based restriction.
AB  - PURPOSE: To develop a method for inverse volumetric-modulated arc therapy (VMAT)
      planning that combines multicriteria optimization (MCO) with direct machine
      parameter optimization. The ultimate goal is to provide an efficient and
      intuitive method for generating high quality VMAT plans. METHODS: Multicriteria
      radiation therapy treatment planning amounts to approximating the relevant
      treatment options by a discrete set of plans, and selecting the combination
      thereof that strikes the best possible balance between conflicting objectives.
      This approach is applied to two decompositions of the inverse VMAT planning
      problem: a fluence-based relaxation considered at a coarsened gantry angle
      spacing and under a regularizing penalty on fluence modulation, and a segment
      weight-based restriction in a neighborhood of the solution to the relaxed
      problem. The two considered variable domains are interconnected by direct machine
      parameter optimization toward reproducing the dose-volume histogram of the
      fluence-based solution. RESULTS: The dose distribution quality of plans generated
      by the proposed MCO method was assessed by direct comparison with benchmark plans
      generated by a conventional VMAT planning method. The results for four patient
      cases (prostate, pancreas, lung, and head and neck) are highly comparable between
      the MCO plans and the benchmark plans: Discrepancies between studied dose-volume
      statistics for organs at risk were-with the exception of the kidneys of the
      pancreas case-within 1 Gy or 1 percentage point. Target coverage of the MCO plans
      was comparable with that of the benchmark plans, but with a small tendency toward
      a shift from conformity to homogeneity. CONCLUSIONS: MCO allows tradeoffs between
      conflicting objectives encountered in VMAT planning to be explored in an
      interactive manner through search over a continuous representation of the
      relevant treatment options. Treatment plans selected from such a representation
      are of comparable dose distribution quality to conventionally optimized VMAT
      plans.

PMID- 23127066
TI  - A pencil beam algorithm for helium ion beam therapy.
AB  - PURPOSE: To develop a flexible pencil beam algorithm for helium ion beam therapy.
      Dose distributions were calculated using the newly developed pencil beam
      algorithm and validated using Monte Carlo (MC) methods. METHODS: The algorithm
      was based on the established theory of fluence weighted elemental pencil beam
      (PB) kernels. Using a new real-time splitting approach, a minimization routine
      selects the optimal shape for each sub-beam. Dose depositions along the beam path
      were determined using a look-up table (LUT). Data for LUT generation were derived
      from MC simulations in water using GATE 6.1. For materials other than water, dose
      depositions were calculated by the algorithm using water-equivalent depth
      scaling. Lateral beam spreading caused by multiple scattering has been accounted
      for by implementing a non-local scattering formula developed by Gottschalk. A new
      nuclear correction was modelled using a Voigt function and implemented by a LUT
      approach. Validation simulations have been performed using a phantom filled with
      homogeneous materials or heterogeneous slabs of up to 3 cm. The beams were
      incident perpendicular to the phantoms surface with initial particle energies
      ranging from 50 to 250 MeV/A with a total number of 10(7) ions per beam. For
      comparison a special evaluation software was developed calculating the gamma
      indices for dose distributions. RESULTS: In homogeneous phantoms, maximum range
      deviations between PB and MC of less than 1.1% and differences in the width of
      the distal energy fall off of the Bragg-Peak from 80% to 20% of less than 0.1 mm
      were found. Heterogeneous phantoms using layered slabs satisfied a gamma-index
      criterion of 2%/2mm of the local value except for some single voxels. For more
      complex phantoms using laterally arranged bone-air slabs, the gamma-index
      criterion was exceeded in some areas giving a maximum gamma-index of 1.75 and
      4.9% of the voxels showed gamma-index values larger than one. The calculation
      precision of the presented algorithm was considered to be sufficient for clinical
      practice. Although only data for helium beams was presented, the performance of
      the pencil beam algorithm for proton beams was comparable. CONCLUSIONS: The
      pencil beam algorithm developed for helium ions presents a suitable tool for dose
      calculations. Its calculation speed was evaluated to be similar to other
      published pencil beam algorithms. The flexible design allows easy customization
      of measured depth-dose distributions and use of varying beam profiles, thus
      making it a promising candidate for integration into future treatment planning
      systems. Current work in progress deals with RBE effects of helium ions to
      complete the model.

PMID- 23127067
TI  - Three-dimensional thermoacoustic imaging for early breast cancer detection.
AB  - PURPOSE: Microwave-induced thermoacoustic tomography (TAT) is a noninvasive
      modality based on the differences in microwave absorption of various biological
      tissues. In this paper, the feasibility of the early breast tumor detection by
      TAT system has been discussed and validated experimentally. METHODS: A fast TAT
      system, which based on three 128-elements transducers, a 384-64ch switch and a
      parallel data acquisition system (DAS), was developed to reconstruct the three
      dimensional (3D) image of a breast model with similar microwave absorption
      coefficient to breast tissue. A novel method to explore the ability of TAT system
      to distinguish absorption coefficient was introduced and the minimum absorption
      coefficient difference that can be distinguished clearly by our TAT system is 12
      m(-1). RESULTS: The potential applications of the TAT system were clearly
      demonstrated by successfully mapping breast model with mimicked tumors and
      microcalcification. An imaging experiment of human breast tumor embedding in the
      breast model was performed and the tumor was visualized by the 3D thermoacoustic
      volume. CONCLUSIONS: The thermoacoustic images match well with the samples and
      achieve penetration depth of 6 cm. The experimental results indicate that TAT has
      a great potential to be used for detecting early-stage breast cancers with high
      contrast and high resolution.

PMID- 23127068
TI  - Fast polyenergetic forward projection for image formation using OpenCL on a
      heterogeneous parallel computing platform.
AB  - PURPOSE: Simulated projection images of digital phantoms constructed from CT
      scans have been widely used for clinical and research applications but their
      quality and computation speed are not optimal for real-time comparison with the
      radiography acquired with an x-ray source of different energies. In this paper,
      the authors performed polyenergetic forward projections using open computing
      language (OpenCL) in a parallel computing ecosystem consisting of CPU and general
      purpose graphics processing unit (GPGPU) for fast and realistic image formation.
      METHODS: The proposed polyenergetic forward projection uses a lookup table
      containing the NIST published mass attenuation coefficients (MU/rho) for
      different tissue types and photon energies ranging from 1 keV to 20 MeV. The CT
      images of interested sites are first segmented into different tissue types based
      on the CT numbers and converted to a three-dimensional attenuation phantom by
      linking each voxel to the corresponding tissue type in the lookup table. The x
      ray source can be a radioisotope or an x-ray generator with a known spectrum
      described as weight w(n) for energy bin E(n). The Siddon method is used to
      compute the x-ray transmission line integral for E(n) and the x-ray fluence is
      the weighted sum of the exponential of line integral for all energy bins with
      added Poisson noise. To validate this method, a digital head and neck phantom
      constructed from the CT scan of a Rando head phantom was segmented into three
      (air, gray/white matter, and bone) regions for calculating the polyenergetic
      projection images for the Mohan 4 MV energy spectrum. To accelerate the
      calculation, the authors partitioned the workloads using the task parallelism and
      data parallelism and scheduled them in a parallel computing ecosystem consisting
      of CPU and GPGPU (NVIDIA Tesla C2050) using OpenCL only. The authors explored the
      task overlapping strategy and the sequential method for generating the first and
      subsequent DRRs. A dispatcher was designed to drive the high-degree parallelism
      of the task overlapping strategy. Numerical experiments were conducted to compare
      the performance of the OpenCL/GPGPU-based implementation with the CPU-based
      implementation. RESULTS: The projection images were similar to typical portal
      images obtained with a 4 or 6 MV x-ray source. For a phantom size of 512 * 512 *
      223, the time for calculating the line integrals for a 512 * 512 image panel was
      16.2 ms on GPGPU for one energy bin in comparison to 8.83 s on CPU. The total
      computation time for generating one polyenergetic projection image of 512 * 512
      was 0.3 s (141 s for CPU). The relative difference between the projection images
      obtained with the CPU-based and OpenCL/GPGPU-based implementations was on the
      order of 10(-6) and was virtually indistinguishable. The task overlapping
      strategy was 5.84 and 1.16 times faster than the sequential method for the first
      and the subsequent digitally reconstruction radiographies, respectively.
      CONCLUSIONS: The authors have successfully built digital phantoms using anatomic
      CT images and NIST MU/rho tables for simulating realistic polyenergetic
      projection images and optimized the processing speed with parallel computing
      using GPGPU/OpenCL-based implementation. The computation time was fast (0.3 s per
      projection image) enough for real-time IGRT (image-guided radiotherapy)
      applications.

PMID- 23127069
TI  - A real-time in vivo dosimetric verification method for high-dose rate
      intracavitary brachytherapy of nasopharyngeal carcinoma.
AB  - PURPOSE: A real-time in vivo dosimetric verification method using metal-oxide
      semiconductor field effect transistor (MOSFET) dosimeters has been developed for
      patient dosimetry in high-dose rate (HDR) intracavitary brachytherapy of
      nasopharyngeal carcinoma (NPC). METHODS: The necessary calibration and correction
      factors for MOSFET measurements in (192)Iridium source were determined in a water
      phantom. With the detector placed inside a custom-made nasopharyngeal applicator,
      the actual dose delivered to the tumor was measured in vivo and compared to the
      calculated values using a commercial brachytherapy planning system. RESULTS: Five
      MOSFETs were independently calibrated with the HDR source, yielding calibration
      factors of 0.48 +/- 0.007 cGy/mV. The maximum sensitivity variation was no more
      than 7% in the clinically relevant distance range of 1-5 cm from the source. A
      total of 70 in vivo measurements in 11 NPC patients demonstrated good agreement
      with the treatment planning. The mean differences between the planned and the
      actually delivered dose within a single treatment fraction were -0.1% +/- 3.8%
      and -0.1% +/- 3.7%, respectively, for right and left side assessments. The
      maximum dose deviation was less than 8.5%. CONCLUSIONS: In vivo measurement using
      the real-time MOSFET dosimetry system is possible to evaluate the actual dose to
      the tumor received by the patient during a treatment fraction and thus can offer
      another line of security to detect and prevent large errors.

PMID- 23127070
TI  - Attenuation-based estimation of patient size for the purpose of size specific
      dose estimation in CT. Part I. Development and validation of methods using the CT
      image.
AB  - PURPOSE: For the purpose of size-specific dose estimation, information regarding
      patient attenuation is required. The purpose of this work is to describe a method
      for measuring patient attenuation and expressing the results in terms of a water
      cylinder, with cross sectional area A(w), which would absorb the same average
      dose as the irradiated patient. The ability to calculate A(w) directly from the
      CT image was validated with Monte Carlo simulations and an analytical model.
      METHODS: A series of virtual cylinders were created with diameters ranging from
      10 to 40 cm and lengths of 40 cm. The cylinders were given an atomic number equal
      to that of water; the density of the cylinders was varied from 0.26 to 1.2
      g/cm(3). The average dose to the cylinders from an axial scan at the longitudinal
      center position was calculated using Monte Carlo simulation and an analytical
      model. The relationship between phantom cross sectional area and calculated dose
      was determined for each density value to determine the dependence of A(w) on
      object attenuation. In addition, A(w) was estimated from the virtual CT images
      based on two derived models expressing the potential dependence of A(w) on object
      attenuation, one model assuming a linear dependence and the other assuming a
      quadratic dependence. Model results were compared with those from the Monte Carlo
      simulation and the analytical dose calculation approach. Virtual thorax and
      abdomen phantoms of adult and pediatric sizes were created, and A(w) was
      estimated using geometrical size parameters or the derived models. The accuracy
      of each approach for estimating A(w) was determined by comparing the average dose
      to the virtual phantom calculated using Monte Carlo simulation to the average
      dose to a water equivalent phantom of cross sectional area A(w). RESULTS: In the
      absence of a bowtie filter, both the Monte Carlo simulation and analytical model
      showed that (A(w)/A) had a quadratic dependence on (MU/MU(w)). However, including
      a bowtie filter in the Monte Carlo simulation altered the relationship, such that
      A(w)/A was linearly dependent on MU/MU(w). Using this relationship, the dose
      absorbed by a water cylinder of area A(w) agreed with the dose absorbed by adult
      and pediatric, thorax and abdomen phantoms to within 6% (mean difference = 0.5 +/
      4.8%). Estimates of A(w) (or the water equivalent diameter D(w)) using only
      anterior-posterior and lateral phantom dimensions led to dose estimates that
      agreed with Monte Carlo-derived dose values within 3% and 6% for the abdomen
      adult and pediatric phantoms, respectively. However, because of density
      differences between lung and tissue, larger differences in dose relative to Monte
      Carlo-derived values were observed in the thorax adult and pediatric phantoms
      (15% and 11%, respectively) when only geometrical parameters were used to
      estimate D(w). CONCLUSIONS: Patient attenuation can be quantified in terms of the
      diameter of a water cylinder that absorbs same average dose as the irradiated
      cross section of the patient. The linear dependence of A(w) on object attenuation
      makes it straightforward to calculate A(w) from a CT image on most operator
      consoles or clinical workstations.

PMID- 23127071
TI  - Attenuation-based estimation of patient size for the purpose of size specific
      dose estimation in CT. Part II. Implementation on abdomen and thorax phantoms
      using cross sectional CT images and scanned projection radiograph images.
AB  - PURPOSE: To estimate attenuation using cross sectional CT images and scanned
      projection radiograph (SPR) images in a series of thorax and abdomen phantoms.
      METHODS: Attenuation was quantified in terms of a water cylinder with cross
      sectional area of A(w) from both the CT and SPR images of abdomen and thorax
      phantoms, where A(w) is the area of a water cylinder that would absorb the same
      dose as the specified phantom. SPR and axial CT images were acquired using a dual
      source CT scanner operated at 120 kV in single-source mode. To use the SPR image
      for estimating A(w), the pixel values of a SPR image were calibrated to physical
      water attenuation using a series of water phantoms. A(w) and the corresponding
      diameter D(w) were calculated using the derived attenuation-based methods (from
      either CT or SPR image). A(w) was also calculated using only geometrical
      dimensions of the phantoms (anterior-posterior and lateral dimensions or cross
      sectional area). RESULTS: For abdomen phantoms, the geometry-based and
      attenuation-based methods gave similar results for D(w). Using only geometric
      parameters, an overestimation of D(w) ranging from 4.3% to 21.5% was found for
      thorax phantoms. Results for D(w) using the CT image and SPR based methods agreed
      with each other within 4% on average in both thorax and abdomen phantoms.
      CONCLUSIONS: Either the cross sectional CT or SPR images can be used to estimate
      patient attenuation in CT. Both are more accurate than use of only geometrical
      information for the task of quantifying patient attenuation. The SPR based method
      requires calibration of SPR pixel values to physical water attenuation and this
      calibration would be best performed by the scanner manufacturer.

PMID- 23127072
TI  - Bidirectional local distance measure for comparing segmentations.
AB  - PURPOSE: To accurately quantify the local difference between two contour surfaces
      in two- or three-dimensional space, a new, robust point-to-surface distance
      measure is developed. METHODS: To evaluate and visualize the local surface
      differences, point-to-surface distance measures have been utilized. However,
      previously well-known point-to-surface distance measures have critical
      shortfalls. Previous distance measures termed "normal distance (ND)," "radial
      distance," or "minimum distance (MD)" can report erroneous results at certain
      points where the surfaces under comparison meet certain conditions. These skewed
      results are due to the monodirectional characteristics of these methods. ComGrad
      distance was also proposed to overcome asymmetric characteristics of previous
      point-to-surface distance measures, but their critical incapability of dealing
      with a fold or concave contours. In this regard, a new distance measure termed
      the bidirectional local distance (BLD) is proposed which minimizes errors of the
      previous methods by taking into account the bidirectional characteristics with
      the forward and backward directions. BLD measure works through three steps which
      calculate the maximum value between the forward minimum distance (FMinD) and the
      backward maximum distance (BMaxD) at each point. The first step calculates the
      FMinD as the minimum distance to the test surface from a point, p(ref) on the
      reference surface. The second step involves calculating the minimum distances at
      every point on the test surface to the reference surface. During the last step,
      the BMaxD is calculated as the maximum distance among the minimum distances found
      at p(ref) on the reference surface. Tests are performed on two- and three
      dimensional artificial contour sets in comparison to MD and ND measure
      techniques. Three-dimensional tests performed on actual liver and head-and-neck
      cancer patients. RESULTS: The proposed BLD measure provides local distances
      between segmentations, even in situations where ND, MD, or ComGrad measures fail.
      In particular, the standard deviation measure is not distorted at certain
      geometries where ND, MD, and ComGrad measures report skewed results. CONCLUSIONS:
      The proposed measure provides more reliable statistics on contour comparisons.
      From the statistics, specific local and global distances can be extracted.
      Bidirectional local distance is a reliable distance measure in comparing two- or
      three-dimensional organ segmentations.

PMID- 23127073
TI  - Graphical representation of the effects on tumor and OAR for determining the
      appropriate fractionation regimen in radiation therapy planning.
AB  - PURPOSE: The authors propose a graphical representation of the relation between
      the effect on the tumor and the damage effect on an organ at risk (OAR) against
      the irradiation dose, as an aid for choosing an appropriate fractionation
      regimen. METHODS: The graphical relation is depicted by the radiation effect on
      the tumor E(1) versus that on an OAR E(0). By observing the features of the E(1)
      vs E(0) relation curve, i.e., convex or concave shape, one can judge whether
      multifractionation is better or not. This method is applied to the linear
      quadratic model (with alpha and beta parameters) as an example. Further, the
      method is extended to the general case for nonuniform dose distribution to the
      OAR, which is frequently seen in clinical situations. RESULTS: The criterion for
      selecting multi- or hypofractionation is based on the relation between the dose
      for the OAR and the alpha/beta ratio of the OAR to the tumor. It is also shown
      that the graphical relation enables us to estimate the final effect after
      multifractionated treatment by plotting a tangent line on the curve. CONCLUSIONS:
      The graphical representation method is of use for improving planning in
      radiotherapy by determining the effective fractionation scheme.

PMID- 23127074
TI  - An analytical method for computing voxel S values for electrons and photons.
AB  - PURPOSE: The use of voxel S values (VSVs) is perhaps the most common approach to
      radiation dosimetry for nonuniform distributions of activity within organs or
      tumors. However, VSVs are currently available only for a limited number of voxel
      sizes and radionuclides. The objective of this study was to develop a general
      method to evaluate them for any spectrum of electrons and photons in any cubic
      voxel dimension of practical interest for clinical dosimetry in targeted
      radionuclide therapy. METHODS: The authors developed a Monte Carlo simulation in
      Geant4 in order to evaluate the energy deposited per disintegration (E(dep)) in a
      voxelized region of soft tissue from monoenergetic electrons (10-2000 keV) or
      photons (10-1000 keV) homogeneously distributed in the central voxel, considering
      voxel dimensions ranging from 3 mm to 10 mm. E(dep) was represented as a function
      of a dimensionless quantity termed the "normalized radius," R(n) = R/l, where l
      is the voxel size and R is the distance from the origin. The authors introduced
      two parametric functions in order to fit the electron and photon results, and
      they interpolated the parameters to derive VSVs for any energy and voxel side
      within the ranges mentioned above. In order to validate the results, the authors
      determined VSV for two radionuclides ((131)I and (89)Sr) and two voxel dimensions
      and they compared them with reference data. A validation study in a simple sphere
      model, accounting for tissue inhomogeneities, is presented. RESULTS: The
      E(dep)(R(n)) for both monoenergetic electrons and photons exhibit a smooth
      variation with energy and voxel size, implying that VSVs for monoenergetic
      electrons or photons may be derived by interpolation over the range of energies
      and dimensions considered. By integration, S values for continuous emission
      spectra from beta(-) decay may be derived as well. CONCLUSIONS: The approach
      allows the determination of VSVs for monoenergetic (Auger or conversion)
      electrons and (x-ray or gamma-ray) photons by means of two functions whose
      parameters can be interpolated from tabular data provided. Through integration,
      it is possible to generalize the method to any continuous (beta) spectrum,
      allowing to calculate VSVs for any electron and photon emitter in a voxelized
      structure.

PMID- 23127075
TI  - TOPAS: an innovative proton Monte Carlo platform for research and clinical
      applications.
AB  - PURPOSE: While Monte Carlo particle transport has proven useful in many areas
      (treatment head design, dose calculation, shielding design, and imaging studies)
      and has been particularly important for proton therapy (due to the conformal dose
      distributions and a finite beam range in the patient), the available general
      purpose Monte Carlo codes in proton therapy have been overly complex for most
      clinical medical physicists. The learning process has large costs not only in
      time but also in reliability. To address this issue, we developed an innovative
      proton Monte Carlo platform and tested the tool in a variety of proton therapy
      applications. METHODS: Our approach was to take one of the already-established
      general purpose Monte Carlo codes and wrap and extend it to create a specialized
      user-friendly tool for proton therapy. The resulting tool, TOol for PArticle
      Simulation (TOPAS), should make Monte Carlo simulation more readily available for
      research and clinical physicists. TOPAS can model a passive scattering or
      scanning beam treatment head, model a patient geometry based on computed
      tomography (CT) images, score dose, fluence, etc., save and restart a phase
      space, provides advanced graphics, and is fully four-dimensional (4D) to handle
      variations in beam delivery and patient geometry during treatment. A custom
      designed TOPAS parameter control system was placed at the heart of the code to
      meet requirements for ease of use, reliability, and repeatability without
      sacrificing flexibility. RESULTS: We built and tested the TOPAS code. We have
      shown that the TOPAS parameter system provides easy yet flexible control over all
      key simulation areas such as geometry setup, particle source setup, scoring
      setup, etc. Through design consistency, we have insured that user experience
      gained in configuring one component, scorer or filter applies equally well to
      configuring any other component, scorer or filter. We have incorporated key
      lessons from safety management, proactively removing possible sources of user
      error such as line-ordering mistakes. We have modeled proton therapy treatment
      examples including the UCSF eye treatment head, the MGH stereotactic alignment in
      radiosurgery treatment head and the MGH gantry treatment heads in passive
      scattering and scanning modes, and we have demonstrated dose calculation based on
      patient-specific CT data. Initial validation results show agreement with measured
      data and demonstrate the capabilities of TOPAS in simulating beam delivery in 3D
      and 4D. CONCLUSIONS: We have demonstrated TOPAS accuracy and usability in a
      variety of proton therapy setups. As we are preparing to make this tool freely
      available for researchers in medical physics, we anticipate widespread use of
      this tool in the growing proton therapy community.

PMID- 23127076
TI  - Design and dosimetric characteristics of a new endocavitary contact radiotherapy
      system using an electronic brachytherapy source.
AB  - PURPOSE: To present design aspects and acceptance tests performed for clinical
      implementation of electronic brachytherapy treatment of early stage rectal
      adenocarcinoma. A dosimetric comparison is made between the historically used
      Philips RT-50 unit and the newly developed Axxent((r)) Model S700 electronic
      brachytherapy source manufactured by Xoft (iCad, Inc.). METHODS: Two proctoscope
      cones were manufactured by ElectroSurgical Instruments (ESI). Two custom surface
      applicators were manufactured by Xoft and were designed to fit and interlock with
      the proctoscope cones from ESI. Dose rates, half value layers (HVL), and
      percentage depth dose (PDD) measurements were made with the Xoft system and
      compared to historical RT-50 data. A description of the patient treatment
      approach and exposure rates during the procedure is also provided. RESULTS: The
      electronic brachytherapy system has a lower surface dose rate than the RT-50. The
      dose rate to water on the surface from the Xoft system is approximately 2.1
      Gy/min while the RT-50 is 10-12 Gy/min. However, treatment times with Xoft are
      still reasonable. The HVLs and PDDs between the two systems were comparable
      resulting in similar doses to the target and to regions beyond the target. The
      exposure rate levels around a patient treatment were acceptable. The standard
      uncertainty in the dose rate to water on the surface is approximately +/-5.2%.
      CONCLUSIONS: The Philips RT-50 unit is an out-of-date radiotherapy machine that
      is no longer manufactured with limited replacement parts. The use of a custom
      designed proctoscope and Xoft surface applicators allows delivery of a well
      established treatment with the ease of a modern radiotherapy device. While the
      dose rate is lower with the use of Xoft, the treatment times are still
      reasonable. Additionally, personnel may stand farther away from the Xoft
      radiation source, thus potentially reducing radiation exposure to the operator
      and other personnel.

PMID- 23127077
TI  - Toward quantifying the composition of soft tissues by spectral CT with Medipix3.
AB  - PURPOSE: To determine the potential of spectral computed tomography (CT) with
      Medipix3 for quantifying fat, calcium, and iron in soft tissues within small
      animal models and surgical specimens of diseases such as fatty liver (metabolic
      syndrome) and unstable atherosclerosis. METHODS: The spectroscopic method was
      applied to tomographic data acquired using a micro-CT system incorporating a
      Medipix3 detector array with silicon sensor layer and microfocus x-ray tube
      operating at 50 kVp. A 10 mm diameter perspex phantom containing a fat surrogate
      (sunflower oil) and aqueous solutions of ferric nitrate, calcium chloride, and
      iodine was imaged with multiple energy bins. The authors used the spectroscopic
      characteristics of the CT number to establish a basis for the decomposition of
      soft tissue components. The potential of the method of constrained least squares
      for quantifying different sets of materials was evaluated in terms of information
      entropy and degrees of freedom, with and without the use of a volume conservation
      constraint. The measurement performance was evaluated quantitatively using
      atheroma and mouse equivalent phantoms. Finally the decomposition method was
      assessed qualitatively using a euthanized mouse and an excised human
      atherosclerotic plaque. RESULTS: Spectral CT measurements of a phantom containing
      tissue surrogates confirmed the ability to distinguish these materials by the
      spectroscopic characteristics of their CT number. The assessment of performance
      potential in terms of information entropy and degrees of freedom indicated that
      certain sets of up to three materials could be decomposed by the method of
      constrained least squares. However, there was insufficient information within the
      data set to distinguish calcium from iron within soft tissues. The quantification
      of calcium concentration and fat mass fraction within atheroma and mouse
      equivalent phantoms by spectral CT correlated well with the nominal values (R(2)
      = 0.990 and R(2) = 0.985, respectively). In the euthanized mouse and excised
      human atherosclerotic plaque, regions of calcium and fat were appropriately
      decomposed according to their spectroscopic characteristics. CONCLUSIONS:
      Spectral CT, using the Medipix3 detector and silicon sensor layer, can quantify
      certain sets of up to three materials using the proposed method of constrained
      least squares. The system has some ability to independently distinguish calcium,
      fat, and water, and these have been quantified within phantom equivalents of
      fatty liver and atheroma. In this configuration, spectral CT cannot distinguish
      iron from calcium within soft tissues.

PMID- 23127078
TI  - A Bayesian nonrigid registration method to enhance intraoperative target
      definition in image-guided prostate procedures through uncertainty
      characterization.
AB  - PURPOSE: This study introduces a probabilistic nonrigid registration method for
      use in image-guided prostate brachytherapy. Intraoperative imaging for prostate
      procedures, usually transrectal ultrasound (TRUS), is typically inferior to
      diagnostic-quality imaging of the pelvis such as endorectal magnetic resonance
      imaging (MRI). MR images contain superior detail of the prostate boundaries and
      provide substructure features not otherwise visible. Previous efforts to register
      diagnostic prostate images with the intraoperative coordinate system have been
      deterministic and did not offer a measure of the registration uncertainty. The
      authors developed a Bayesian registration method to estimate the posterior
      distribution on deformations and provide a case-specific measure of the
      associated registration uncertainty. METHODS: The authors adapted a biomechanical
      based probabilistic nonrigid method to register diagnostic to intraoperative
      images by aligning a physician's segmentations of the prostate in the two images.
      The posterior distribution was characterized with a Markov Chain Monte Carlo
      method; the maximum a posteriori deformation and the associated uncertainty were
      estimated from the collection of deformation samples drawn from the posterior
      distribution. The authors validated the registration method using a dataset
      created from ten patients with MRI-guided prostate biopsies who had both
      diagnostic and intraprocedural 3 Tesla MRI scans. The accuracy and precision of
      the estimated posterior distribution on deformations were evaluated from two
      predictive distance distributions: between the deformed central zone-peripheral
      zone (CZ-PZ) interface and the physician-labeled interface, and based on
      physician-defined landmarks. Geometric margins on the registration of the
      prostate's peripheral zone were determined from the posterior predictive distance
      to the CZ-PZ interface separately for the base, mid-gland, and apical regions of
      the prostate. RESULTS: The authors observed variation in the shape and volume of
      the segmented prostate in diagnostic and intraprocedural images. The
      probabilistic method allowed us to convey registration results in terms of
      posterior distributions, with the dispersion providing a patient-specific
      estimate of the registration uncertainty. The median of the predictive distance
      distribution between the deformed prostate boundary and the segmented boundary
      was <=3 mm (95th percentiles within +/-4 mm) for all ten patients. The accuracy
      and precision of the internal deformation was evaluated by comparing the
      posterior predictive distance distribution for the CZ-PZ interface for each
      patient, with the median distance ranging from -0.6 to 2.4 mm. Posterior
      predictive distances between naturally occurring landmarks showed registration
      errors of <=5 mm in any direction. The uncertainty was not a global measure, but
      instead was local and varied throughout the registration region. Registration
      uncertainties were largest in the apical region of the prostate. CONCLUSIONS:
      Using a Bayesian nonrigid registration method, the authors determined the
      posterior distribution on deformations between diagnostic and intraprocedural MR
      images and quantified the uncertainty in the registration results. The
      feasibility of this approach was tested and results were positive. The
      probabilistic framework allows us to evaluate both patient-specific and location
      specific estimates of the uncertainty in the registration result. Although the
      framework was tested on MR-guided procedures, the preliminary results suggest
      that it may be applied to TRUS-guided procedures as well, where the addition of
      diagnostic MR information may have a larger impact on target definition and
      clinical guidance.

PMID- 23127079
TI  - Quantitative analysis of the factors which affect the interpatient organ-at-risk
      dose sparing variation in IMRT plans.
AB  - PURPOSE: The authors present an evidence-based approach to quantify the effects
      of an array of patient anatomical features of the planning target volumes (PTVs)
      and organs-at-risk (OARs) and their spatial relationships on the interpatient OAR
      dose sparing variation in intensity modulated radiation therapy (IMRT) plans by
      learning from a database of high-quality prior plans. METHODS: The authors
      formulized the dependence of OAR dose volume histograms (DVHs) on patient
      anatomical factors into feature models which were learned from prior plans by a
      stepwise multiple regression method. IMRT plans for 64 prostate, 82 head-and-neck
      (HN) treatments were used to train the models. Two major groups of anatomical
      features were considered in this study: the volumetric information and the
      spatial information. The geometry of OARs relative to PTV is represented by the
      distance-to-target histogram, DTH. Important anatomical and dosimetric features
      were extracted from DTH and DVH by principal component analysis. The final models
      were tested by additional 24 prostate and 24 HN plans. RESULTS: Significant
      patient anatomical factors contributing to OAR dose sparing in prostate and HN
      IMRT plans have been analyzed and identified. They are: the median distance
      between OAR and PTV, the portion of OAR volume within an OAR specific distance
      range, and the volumetric factors: the fraction of OAR volume which overlaps with
      PTV and the portion of OAR volume outside the primary treatment field. Overall,
      the determination coefficients R(2) for predicting the first principal component
      score (PCS1) of the OAR DVH by the above factors are above 0.68 for all the OARs
      and they are more than 0.53 for predicting the second principal component score
      (PCS2) of the OAR DVHs except brainstem and spinal cord. Thus, the above set of
      anatomical features combined has captured significant portions of the DVH
      variations for the OARs in prostate and HN plans. To test how well these features
      capture the interpatient organ dose sparing variations in general, the DVHs and
      specific dose-volume indices calculated from the regression models were compared
      with the actual DVHs and dose-volume indices from each patient's plan in the
      validation dataset. The dose-volume indices compared were V99%, V85%, and V50%
      for bladder and rectum in prostate plans and parotids median dose in HN plans.
      The authors found that for the bladder and rectum models, 17 out of 24 plans
      (71%) were within 6% OAR volume error and 21 plans (85%) were within 10% error;
      For the parotids model, the median dose values for 30 parotids out of 48 (63%)
      were within 6% prescription dose error and the values in 40 parotids (83%) were
      within 10% error. CONCLUSIONS: Quantitative analysis of patient anatomical
      features and their correlation with OAR dose sparing has identified a number of
      important factors that explain significant amount of interpatient DVH variations
      in OARs. These factors can be incorporated into evidence-based learning models as
      effective features to provide patient-specific OAR dose sparing goals.

PMID- 23127080
TI  - Validation of deformable registration in head and neck cancer using analysis of
      variance.
AB  - PURPOSE: Deformable image registration (DIR) is often validated based on a
      distance-to-agreement (DTA) criterion of automatically propagated anatomical
      landmarks that were manually identified. Due to human observer variability,
      however, the performance of the registration method is diluted. The purpose of
      this study was to evaluate an analysis of variance (ANOVA) based validation to
      account for such observer variation. METHODS: Weekly cone beam CTs (CBCTs) of ten
      head and neck cancer patients undergoing five weeks of radiotherapy were used. An
      expert identified 23 anatomical features (landmarks) on the planning CT. The
      landmarks were automatically propagated to the CBCT using multiregion-of-interest
      (mROI) registration. Additionally, two human observers independently localized
      these landmarks on the CBCTs. Subsequently, ANOVA was used to compute the
      variance of each observer on the pairwise distance (PWD). RESULTS: ANOVA based
      analysis demonstrated that a classical DTA approach underestimated the precision
      for the mROI due to human observer variation by about 25%. The systematic error
      (accuracy) of mROI ranged from 0.13 to 0.17 mm; the variability (1 SD)
      (precision) ranged from 1.3 to 1.5 mm demonstrating that its performance is
      dominated by the precision. CONCLUSIONS: The PWD-ANOVA method accounts for human
      observer variation allowing a better estimation of the of DIR errors.

PMID- 23127081
TI  - Quality correction factors of composite IMRT beam deliveries: theoretical
      considerations.
AB  - PURPOSE: In the scope of intensity modulated radiation therapy (IMRT) dosimetry
      using ionization chambers, quality correction factors of plan-class-specific
      reference (PCSR) fields are theoretically investigated. The symmetry of the
      problem is studied to provide recommendable criteria for composite beam
      deliveries where correction factors are minimal and also to establish a
      theoretical limit for PCSR delivery k(Q) factors. METHODS: The concept of virtual
      symmetric collapsed (VSC) beam, being associated to a given modulated composite
      delivery, is defined in the scope of this investigation. Under symmetrical
      measurement conditions, any composite delivery has the property of having a k(Q)
      factor identical to its associated VSC beam. Using this concept of VSC, a
      fundamental property of IMRT k(Q) factors is demonstrated in the form of a
      theorem. The sensitivity to the conditions required by the theorem is thoroughly
      examined. RESULTS: The theorem states that if a composite modulated beam delivery
      produces a uniform dose distribution in a volume V(cyl) which is symmetric with
      the cylindrical delivery and all beams fulfills two conditions in V(cyl): (1) the
      dose modulation function is unchanged along the beam axis, and (2) the dose
      gradient in the beam direction is constant for a given lateral position; then its
      associated VSC beam produces no lateral dose gradient in V(cyl), no matter what
      beam modulation or gantry angles are being used. The examination of the
      conditions required by the theorem lead to the following results. The effect of
      the depth-dose gradient not being perfectly constant with depth on the VSC beam
      lateral dose gradient is found negligible. The effect of the dose modulation
      function being degraded with depth on the VSC beam lateral dose gradient is found
      to be only related to scatter and beam hardening, as the theorem holds also for
      diverging beams. CONCLUSIONS: The use of the symmetry of the problem in the
      present paper leads to a valuable theorem showing that k(Q) factors of composite
      IMRT beam deliveries are close to unity under specific conditions. The
      theoretical limit k(Q(pcsr),Q(msr) ) (f(pcsr),f(msr) )=1 is determined based on
      the property of PCSR deliveries to provide a uniform dose in the target volume.
      The present approach explains recent experimental observations and proposes ideal
      conditions for IMRT reference dosimetry. The result of this study could
      potentially serve as a theoretical basis for reference dosimetry of composite
      IMRT beam deliveries or for routine IMRT quality assurance.

PMID- 23127082
TI  - A calibration-free, one-step method for quantitative photoacoustic tomography.
AB  - PURPOSE: Recently reported quantitative photoacoustic tomography (PAT) has
      significantly expanded the utilities of PAT because it allows for recovery of
      tissue optical absorption coefficient which directly correlates with tissue
      physiological information. However, the recovery of optical absorption
      coefficient by the existing quantitative PAT approaches strongly depends on the
      accuracy of absorbed energy density distribution, and on the knowledge of
      accurate strength and distribution of incident light source. The purpose of this
      study is to develop a new algorithm for the reconstruction of optical absorption
      coefficient that does not depend on these initial parameters. METHODS: Here the
      authors propose a novel one-step reconstruction approach that can directly
      recover optical absorption coefficient from photoacoustic measurements along
      boundary domain. The authors validate the method using simulation and phantom
      experiments. RESULTS: The authors have demonstrated experimental evidence that it
      is possible to directly recover optical absorption coefficient maps using
      boundary photoacoustic measurements coupled with the photon diffusion equation in
      just one step. The authors found that the method described is able to
      quantitatively reconstruct absorbing objects with different sizes and optical
      contrast levels. CONCLUSIONS: Compared to the authors' previous two-step methods,
      the reconstruction results obtained here show that the one-step scheme can
      significantly improve the accuracy of absorption coefficient recovery.

PMID- 23127083
TI  - Performance comparison of high quantum efficiency and normal quantum efficiency
      photomultiplier tubes and position sensitive photomultiplier tubes for high
      resolution PET and SPECT detectors.
AB  - PURPOSE: Recently, photomultiplier tubes (PMTs) and position sensitive PMTs
      (PSPMTs) with higher quantum efficiencies (HQE) have been developed. However, it
      remains unclear whether they actually improve such performances as the energy and
      spatial resolution for PET and SPECT detectors. METHODS: The authors evaluated
      the quantum efficiencies (QEs) for PMTs and PSPMTs and measured the energy
      resolution of a 3-in. round HQE PMT combined with various scintillators and
      compared the results with a conventional normal quantum efficiency (NQE) PMT of
      the same type. The authors also measured the position and energy performance of a
      2-in. square HQE PSPMT combined with scintillator blocks and compared them with a
      NQE PSPMT of the same size. RESULTS: The energy resolution of the 3-in. round HQE
      PMT showed higher energy resolution than the NQE with all scintillators. The
      improvement of the energy resolution was smaller, for all measurements, than the
      expected value from the quantum efficiency of the PMT but was higher for the
      scintillators with smaller light outputs. The energy and position performance of
      the HQE PSPMT based block detectors showed higher position and energy performance
      than those with NQE. CONCLUSIONS: From these results, the authors conclude that
      both HQE PMT and PSPMT contribute to improve the energy and position performance
      for PET and SPECT detectors. Significant performance improvements will be
      expected in PET and SPECT systems by the use of the HQE PMTs or PSPMTs.

PMID- 23127084
TI  - Quality assurance and independent dosimetry for an intraoperative x-ray device.
AB  - PURPOSE: Quality assurance is an essential component of accurate and safe
      radiotherapy delivery, and should include measurements which are independent of
      manufacturer-provided calibration. However, the physical and dosimetric
      properties of the INTRABEAM compact mobile 50 kV x-ray source are different from
      conventional kilovoltage therapy units and few reports describe methods for
      independent checks, frequencies, or tolerances for quality assurance tests.
      METHODS: Based on the available evidence and local experience, methods are
      described for determination of the key dosimetric parameters: beam quality,
      output, isotropy, and depth doses. Internal system checks are also described,
      along with measurements of long-term stability. RESULTS: A small volume parallel
      plate ionization chamber in a liquid water tank is the gold standard for
      measurements with this unit, but solid water-equivalent materials,
      thermoluminescent dosimeters and radiochromic film can all be used as practical
      alternatives with an accuracy of 5%-10%. The main cause of measurement
      uncertainty is positioning of the detector in the steep dose gradient, but energy
      dependence should also be considered. CONCLUSIONS: A quality assurance schedule
      with suggested tolerances is proposed, which includes both internal tests, before
      each treatment and on a monthly basis, and independent tests every year or after
      servicing or recalibration.

PMID- 23127085
TI  - Audiovisual biofeedback improves diaphragm motion reproducibility in MRI.
AB  - PURPOSE: In lung radiotherapy, variations in cycle-to-cycle breathing results in
      four-dimensional computed tomography imaging artifacts, leading to inaccurate
      beam coverage and tumor targeting. In previous studies, the effect of audiovisual
      (AV) biofeedback on the external respiratory signal reproducibility has been
      investigated but the internal anatomy motion has not been fully studied. The aim
      of this study is to test the hypothesis that AV biofeedback improves diaphragm
      motion reproducibility of internal anatomy using magnetic resonance imaging
      (MRI). METHODS: To test the hypothesis 15 healthy human subjects were enrolled in
      an ethics-approved AV biofeedback study consisting of two imaging sessions spaced
      ~1 week apart. Within each session MR images were acquired under free breathing
      and AV biofeedback conditions. The respiratory signal to the AV biofeedback
      system utilized optical monitoring of an external marker placed on the abdomen.
      Synchronously, serial thoracic 2D MR images were obtained to measure the
      diaphragm motion using a fast gradient-recalled-echo MR pulse sequence in both
      coronal and sagittal planes. The improvement in the diaphragm motion
      reproducibility using the AV biofeedback system was quantified by comparing cycle
      to-cycle variability in displacement, respiratory period, and baseline drift.
      Additionally, the variation in improvement between the two sessions was also
      quantified. RESULTS: The average root mean square error (RMSE) of diaphragm cycle
      to-cycle displacement was reduced from 2.6 mm with free breathing to 1.6 mm (38%
      reduction) with the implementation of AV biofeedback (p-value < 0.0001). The
      average RMSE of the respiratory period was reduced from 1.7 s with free breathing
      to 0.3 s (82% reduction) with AV biofeedback (p-value < 0.0001). Additionally,
      the average baseline drift obtained using a linear fit was reduced from 1.6
      mm/min with free breathing to 0.9 mm/min (44% reduction) with AV biofeedback (p
      value = 0.012). The diaphragm motion reproducibility improvements with AV
      biofeedback were consistent with the abdominal motion reproducibility that was
      observed from the external marker motion variation. CONCLUSIONS: This study was
      the first to investigate the potential of AV biofeedback to improve the motion
      reproducibility of internal anatomy using MRI. The study demonstrated the
      significant improvement in diaphragm motion reproducibility using AV biofeedback
      combined with MRI. This system can potentially provide clinically beneficial
      motion management of internal anatomy in MRI and radiotherapy.

PMID- 23127086
TI  - Content-based retrieval of brain tumor in contrast-enhanced MRI images using
      tumor margin information and learned distance metric.
AB  - PURPOSE: A content-based image retrieval (CBIR) method for T1-weighted contrast
      enhanced MRI (CE-MRI) images of brain tumors is presented for diagnosis aid. The
      method is thoroughly evaluated on a large image dataset. METHODS: Using the tumor
      region as a query, the authors' CBIR system attempts to retrieve tumors of the
      same pathological category. Aside from commonly used features such as intensity,
      texture, and shape features, the authors use a margin information descriptor
      (MID), which is capable of describing the characteristics of tissue surrounding a
      tumor, for representing image contents. In addition, the authors designed a
      distance metric learning algorithm called Maximum mean average Precision
      Projection (MPP) to maximize the smooth approximated mean average precision (mAP)
      to optimize retrieval performance. RESULTS: The effectiveness of MID and MPP
      algorithms was evaluated using a brain CE-MRI dataset consisting of 3108 2D scans
      acquired from 235 patients with three categories of brain tumors (meningioma,
      glioma, and pituitary tumor). By combining MID and other features, the mAP of
      retrieval increased by more than 6% with the learned distance metrics. The
      distance metric learned by MPP significantly outperformed the other two existing
      distance metric learning methods in terms of mAP. The CBIR system using the
      proposed strategies achieved a mAP of 87.3% and a precision of 89.3% when top 10
      images were returned by the system. Compared with scale-invariant feature
      transform, the MID, which uses the intensity profile as descriptor, achieves
      better retrieval performance. CONCLUSIONS: Incorporating tumor margin information
      represented by MID with the distance metric learned by the MPP algorithm can
      substantially improve the retrieval performance for brain tumors in CE-MRI.

PMID- 23127087
TI  - 4D cone beam CT via spatiotemporal tensor framelet.
AB  - PURPOSE: On-board 4D cone beam CT (4DCBCT) offers respiratory phase-resolved
      volumetric imaging, and improves the accuracy of target localization in image
      guided radiation therapy. However, the clinical utility of this technique has
      been greatly impeded by its degraded image quality, prolonged imaging time, and
      increased imaging dose. The purpose of this letter is to develop a novel
      iterative 4DCBCT reconstruction method for improved image quality, increased
      imaging speed, and reduced imaging dose. METHODS: The essence of this work is to
      introduce the spatiotemporal tensor framelet (STF), a high-dimensional tensor
      generalization of the 1D framelet for 4DCBCT, to effectively take into account of
      highly correlated and redundant features of the patient anatomy during
      respiration, in a multilevel fashion with multibasis sparsifying transform. The
      STF-based algorithm is implemented on a GPU platform for improved computational
      efficiency. To evaluate the method, 4DCBCT full-fan scans were acquired within 30
      s, with a gantry rotation of 200 degrees ; STF is also compared with a state-of
      art reconstruction method via spatiotemporal total variation regularization.
      RESULTS: Both the simulation and experimental results demonstrate that STF-based
      reconstruction achieved superior image quality. The reconstruction of 20
      respiratory phases took less than 10 min on an NVIDIA Tesla C2070 GPU card. The
      STF codes are available at
      https://sites.google.com/site/spatiotemporaltensorframelet. CONCLUSIONS: By
      effectively utilizing the spatiotemporal coherence of the patient anatomy among
      different respiratory phases in a multilevel fashion with multibasis sparsifying
      transform, the proposed STF method potentially enables fast and low-dose 4DCBCT
      with improved image quality.

PMID- 23127088
TI  - Impact of the number of discrete angles used during dose computation for
      TomoTherapy treatments.
AB  - PURPOSE: To quantify systematically the effect on accuracy of discretizing gantry
      rotation during the dose calculation process of TomoTherapy treatments. METHODS:
      Up to version 4.0.x included, TomoTherapy treatment planning system (TPS)
      approximates gantry rotation by computing dose from 51 discrete angles
      corresponding to the center of the projections used to control the binary
      multileaf collimator. Potential effects on dose computation accuracy for off-axis
      targets and low modulation factors have been shown previously for a few treatment
      configurations. In versions 4.1.x and later, TomoTherapy oversamples the
      projections to better account for gantry rotation, but only during full scatter
      optimization and final calculation (i.e., not during optimization in "beamlet"
      mode). The effect on accuracy of changing the number of angles was quantified
      with the following framework: (1) predict the impact of the discretization of
      gantry rotation for various modulation factors, target sizes, and off-axis
      positions using a simplified analytical algorithm; (2) perform regular quality
      assurance using measurements with EDR2 radiographic films; (3) isolating the
      effect of changing the number of discretized angles only (51, 153, and 459) using
      a previously validated Monte Carlo model (TomoPen). The diameters of the targets
      were 2, 3, and 5 cm; off-axis central positions of target volumes were 5, 10 and
      15, and 17 cm (when accepted by the treatment unit); planned modulation factors
      were 1.3 and 2.0. RESULTS: For extreme configurations (3 cm tumor, 1.3 modulation
      factor, 15 cm off-axis position), effects on dose distributions were significant
      with 89.3% and 95.4% of the points passing gamma tests with 2%/2 mm and 3%/3 mm
      criteria, respectively, for TPS software version 4.0.x (51 gantry angles). The
      passing rate was 100% for both gamma criteria for the 4.1.x version (153 gantry
      angles). Those differences could be attributed almost completely to gantry motion
      discretization using TomoPen. Using 51 gantry angles for dose computation,
      TomoPen reproduced within statistical uncertainties (<1% standard deviation) dose
      distributions computed with version 4.0.x. Using 153 and 459 gantry angles,
      TomoPen reproduced within statistical uncertainties measurements and dose
      distributions computed with version 4.1.x. CONCLUSIONS: When low modulation
      factors and significant off-axis positions are used, accounting for gantry
      rotation during dose computation using at least 153 gantry angles is required to
      ensure optimal accuracy.

PMID- 23127089
TI  - Implementation and experimental results of 4D tumor tracking using robotic couch.
AB  - PURPOSE: This study presents the implementation and experimental results of a
      novel technique for 4D tumor tracking using a commercially available and commonly
      used treatment couch and evaluates the tumor tracking accuracy in clinical
      settings. METHODS: Commercially available couch is capable of positioning the
      patient accurately; however, currently there is no provision for compensating
      physiological movement using the treatment couch in real-time. In this paper, a
      real-time couch tracking control technique is presented together with
      experimental results in tumor motion compensation in four dimensions (superior
      inferior, lateral, anterior-posterior, and time). To implement real-time couch
      motion for tracking, a novel control system for the treatment couch was
      developed. The primary functional requirements for this novel technique were: (a)
      the treatment couch should maintain all previous/normal features for patient
      setup and positioning, (b) the new control system should be used as a parallel
      system when tumor tracking would be deployed, and (c) tracking could be performed
      in a single direction and/or concurrently in all three directions of the couch
      motion (longitudinal, lateral, and vertical). To the authors' best knowledge, the
      implementation of such technique to a regular treatment couch for tumor tracking
      has not been reported so far. To evaluate the performance of the tracking couch,
      we investigated the mechanical characteristics of the system such as system
      positioning resolution, repeatability, accuracy, and tracking performance.
      Performance of the tracking system was evaluated using dosimetric test as an
      endpoint. To investigate the accuracy of real-time tracking in the clinical
      setting, the existing clinical treatment couch was replaced with our experimental
      couch and the linear accelerator was used to deliver 3D conformal radiation
      therapy (3D-CRT) and intensity modulated radiation therapy (IMRT) treatment plans
      with and without tracking. The results of radiation dose distribution from these
      two sets of experiments were compared and presented here. RESULTS: The mechanical
      accuracies were 0.12, 0.14, and 0.18 mm in X, Y, and Z directions. The
      repeatability of the desired motion was within +/-0.2 mm. The differences of
      central axis dose between the 3D-CRT stationary plan and two tracking plans with
      different motion trajectories were 0.21% and 1.19%. The absolute dose differences
      of both 3D tracking plans comparing to the stationary plan were 1.09% and 1.20%.
      Comparing the stationary IMRT plan with the tracking IMRT plan, it was observed
      that the central axis dose difference was -0.87% and the absolute difference of
      both IMRT plans was 0.55%. CONCLUSIONS: The experimental results revealed that
      the treatment couch could be successfully used for real-time tumor tracking with
      a high level of accuracy. It was demonstrated that 4D tumor tracking was feasible
      using existing couch with implementation of appropriate tracking methodology and
      with modifications in the control system.

PMID- 23127090
TI  - Prevention of a wrong-location misadministration through the use of an
      intradepartmental incident learning system.
AB  - PURPOSE: A series of examples are presented in which potential errors in the
      delivery of radiation therapy were prevented through use of incident learning.
      These examples underscore the value of reporting near miss incidents. METHODS:
      Using a departmental incident learning system, eight incidents were noted over a
      two-year period in which fields were treated "out-of-sequence," that is, fields
      from a boost phase were treated, while the patient was still in the initial phase
      of treatment. As a result, an error-prevention policy was instituted in which
      radiation treatment fields are "hidden" within the oncology information system
      (OIS) when they are not in current use. In this way, fields are only available to
      be treated in the intended sequence and, importantly, old fields cannot be
      activated at the linear accelerator control console. RESULTS: No out-of-sequence
      treatments have been reported in more than two years since the policy change.
      Furthermore, at least three near-miss incidents were detected and corrected as a
      result of the policy change. In the first two, the policy operated as intended to
      directly prevent an error in field scheduling. In the third near-miss, the policy
      operated "off target" to prevent a type of error scenario that it was not
      directly intended to prevent. In this incident, an incorrect digitally
      reconstructed radiograph (DRR) was scheduled in the OIS for a patient receiving
      lung cancer treatment. The incorrect DRR had an isocenter which was misplaced by
      approximately two centimeters. The error was a result of a field from an old plan
      being scheduled instead of the intended new plan. As a result of the policy
      described above, the DRR field could not be activated for treatment however and
      the error was discovered and corrected. Other quality control barriers in place
      would have been unlikely to have detected this error. CONCLUSIONS: In these
      examples, a policy was adopted based on incident learning, which prevented
      several errors, at least one of which was potentially severe. These examples
      underscore the need for a rigorous, systematic incident learning process within
      each clinic. The experiences reported in this technical note demonstrate the
      value of near-miss incident reporting to improve patient safety.

PMID- 23127091
TI  - Measurement and correction of leaf open times in helical tomotherapy.
AB  - PURPOSE: The binary multileaf collimator (MLC) is one of the most important
      components in helical tomotherapy (HT), as it modulates the dose delivered to the
      patient. However, methods to ensure MLC quality in HT treatments are lacking. The
      authors obtained data on the performance of the MLC in treatments administered in
      their department in order to assess possible delivery errors due to the MLC.
      Correction methods based on their data are proposed. METHODS: Twenty sinograms
      from treatments delivered using both of the authors HT systems were measured and
      analyzed by recording the fluence collected by the imaging detector. Planned and
      actual sinograms were compared using distributions of leaf open time (LOT)
      errors, as well as differences in fluence reconstructed at each of the 51
      projections into which the treatment planning system divides each rotation for
      optimization purposes. They proposed and applied a method based on individual
      leaf error correction and the increase in projection time to prevent latency
      effects when LOT is close to projection time. In order to analyze the dosimetric
      impact of the corrections, inphantom measurements were made for four corrected
      treatments. RESULTS: The LOTs measured were consistent with those planned. Most
      of the mean errors in LOT distributions were within 1 ms with standard deviations
      of over 4 ms. Reconstructed fluences showed good results, with over 90% of points
      passing the 3% criterion, except in treatments with a short mean LOT, where the
      percentage of passing points was as low as 66%. Individual leaf errors were as
      long as 4 ms in some cases. Corrected sinograms improved error distribution, with
      standard deviations of over 3 ms and increased percentages of points passing 3%
      in the fluence per angle analysis, especially in treatments with a short mean LOT
      and those that were more subject to latency effects. The minimum percentage of
      points within 3% increased to 86%. In-phantom measurements of the corrected
      treatments showed that, while treatments affected by latency effects were
      improved, those affected by individual leaf errors were not. CONCLUSIONS:
      Measurement of MLC performance in real treatments provides the authors with a
      valuable tool for ensuring the quality of HT delivery. The LOTs of MLC are very
      accurate in most cases. Sources of error were found and correction methods
      proposed and applied. The corrections decreased the amount of LOT errors. The
      dosimetric impact of these corrections should be evaluated more thoroughly using
      3D dose distribution analysis.

PMID- 23127092
TI  - Commissioning and dosimetric characteristics of TrueBeam system: composite data
      of three TrueBeam machines.
AB  - PURPOSE: A TrueBeam linear accelerator (TB-LINAC) is designed to deliver
      traditionally flattened and flattening-filter-free (FFF) beams. Although it has
      been widely adopted in many clinics for patient treatment, limited information is
      available related to commissioning of this type of machine. In this work,
      commissioning data of three units were measured, and multiunit comparison was
      presented to provide valuable insights and reliable evaluations on the
      characteristics of the new treatment system. METHODS: The TB-LINAC is equipped
      with newly designed waveguide, carousel assembly, monitoring control, and
      integrated imaging systems. Each machine in this study has 4, 6, 8, 10, 15 MV
      flattened photon beams, and 6 MV and 10 MV FFF photon beams as well as 6, 9, 12,
      16, 20, and 22 MeV electron beams. Dosimetric characteristics of the three new TB
      LINAC treatment units are systematically measured for commissioning. High
      resolution diode detectors and ion chambers were used to measure dosimetric data
      for a range of field sizes from 10 * 10 to 400 * 400 mm(2). The composite
      dosimetric data of the three units are presented in this work. The commissioning
      of intensity modulated radiotherapy (IMRT), volumetric modulated arc therapy
      (VMAT), image-guided radiation therapy, and gating systems are also illustrated.
      Critical considerations of P(ion) of FFF photon beams and small field dosimetric
      measurements were investigated. RESULTS: The authors found all PDDs and profiles
      matched well among the three machines. Beam data were quantitatively compared and
      combined through average to yield composite beam data. The discrepancies among
      the machines were quantified using standard deviation (SD). The mean SD of the
      PDDs among the three units is 0.12%, and the mean SD of the profiles is 0.40% for
      10 MV FFF open fields. The variations of P(ion) of the chamber CC13 is 1.2 +/-
      0.1% under 6 MV FFF and 2.0 +/- 0.5% under 10 MV FFF from dmax to the 18 cm-off
      axis point at 35 cm depth under 40 * 40 cm(2). The mean penumbra of crossplane
      flattened photon beams at collimator angle of 0 degrees  is measured from 5.88 +/
      0.09 to 5.99 +/- 0.13 mm from 4 to 15 MV at 10 cm depth of 100 * 100 mm(2). The
      mean penumbra of crossplane beams at collimator angle of 0 degrees  is measured
      as 3.70 +/- 0.21 and 4.83 +/- 0.04 mm for 6 MV FFF and 10 MV FFF, respectively,
      at 10 cm depth with a field size of 5 * 5 cm(2). The end-to-end test procedures
      of both IMRT and VMAT were performed for various energy modes. The mean ion
      chamber measurements of three units showed less than 2% between measurement and
      calculation; the mean MultiCube ICA measurements demonstrated over 90% pixels
      passing gamma analysis (3%, 3 mm, 5% threshold). The imaging dosimetric data of
      KV planar imaging and CBCT demonstrated improved consistency with vendor
      specifications and dose reduction for certain imaging protocols. The gated output
      verification showed a discrepancy of 0.05% or less between gating radiation
      delivery and nongating radiation delivery. CONCLUSIONS: The commissioning data
      indicated good consistency among the three TB-LINAC units. The commissioning data
      provided us valuable insights and reliable evaluations on the characteristics of
      the new treatment system. The systematically measured data might be useful for
      future reference.

PMID- 23127093
TI  - An image-based technique to assess the perceptual quality of clinical chest
      radiographs.
AB  - PURPOSE: Current clinical image quality assessment techniques mainly analyze
      image quality for the imaging system in terms of factors such as the capture
      system modulation transfer function, noise power spectrum, detective quantum
      efficiency, and the exposure technique. While these elements form the basic
      underlying components of image quality, when assessing a clinical image,
      radiologists seldom refer to these factors, but rather examine several specific
      regions of the displayed patient images, further impacted by a particular image
      processing method applied, to see whether the image is suitable for diagnosis. In
      this paper, the authors developed a novel strategy to simulate radiologists'
      perceptual evaluation process on actual clinical chest images. METHODS: Ten
      regional based perceptual attributes of chest radiographs were determined through
      an observer study. Those included lung grey level, lung detail, lung noise, rib
      lung contrast, rib sharpness, mediastinum detail, mediastinum noise, mediastinum
      alignment, subdiaphragm-lung contrast, and subdiaphragm area. Each attribute was
      characterized in terms of a physical quantity measured from the image
      algorithmically using an automated process. A pilot observer study was performed
      on 333 digital chest radiographs, which included 179 PA images with 10:1 ratio
      grids (set 1) and 154 AP images without grids (set 2), to ascertain the
      correlation between image perceptual attributes and physical quantitative
      measurements. To determine the acceptable range of each perceptual attribute, a
      preliminary quality consistency range was defined based on the preferred 80% of
      images in set 1. Mean value difference (MU(1) - MU(2)) and variance ratio
      (sigma(1) (2)/sigma(2) (2)) were investigated to further quantify the differences
      between the selected two image sets. RESULTS: The pilot observer study
      demonstrated that our regional based physical quantity metrics of chest
      radiographs correlated very well with their corresponding perceptual attributes.
      The distribution comparisons, mean value difference estimations, and variance
      ratio estimations of each physical quantity between sets of images from two
      different techniques matched our expectation that the image quality of set 1
      should be better than that of set 2. CONCLUSIONS: The measured physical
      quantities provide a robust reflection of perceptual image quality in clinical
      images. The methodology can be readily applied for automated evaluation of
      perceptual image quality in clinical chest radiographs.

PMID- 23127095
TI  - A fully 3D approach for metal artifact reduction in computed tomography.
AB  - PURPOSE: In computed tomography imaging metal objects in the region of interest
      introduce inconsistencies during data acquisition. Reconstructing these data
      leads to an image in spatial domain including star-shaped or stripe-like
      artifacts. In order to enhance the quality of the resulting image the influence
      of the metal objects can be reduced. Here, a metal artifact reduction (MAR)
      approach is proposed that is based on a recomputation of the inconsistent
      projection data using a fully three-dimensional Fourier-based interpolation. The
      success of the projection space restoration depends sensitively on a sensible
      continuation of neighboring structures into the recomputed area. Fortunately,
      structural information of the entire data is inherently included in the Fourier
      space of the data. This can be used for a reasonable recomputation of the
      inconsistent projection data. METHODS: The key step of the proposed MAR strategy
      is the recomputation of the inconsistent projection data based on an
      interpolation using nonequispaced fast Fourier transforms (NFFT). The NFFT
      interpolation can be applied in arbitrary dimension. The approach overcomes the
      problem of adequate neighborhood definitions on irregular grids, since this is
      inherently given through the usage of higher dimensional Fourier transforms.
      Here, applications up to the third interpolation dimension are presented and
      validated. Furthermore, prior knowledge may be included by an appropriate damping
      of the transform during the interpolation step. This MAR method is applicable on
      each angular view of a detector row, on two-dimensional projection data as well
      as on three-dimensional projection data, e.g., a set of sequential acquisitions
      at different spatial positions, projection data of a spiral acquisition, or cone
      beam projection data. RESULTS: Results of the novel MAR scheme based on one-, two
      , and three-dimensional NFFT interpolations are presented. All results are
      compared in projection data space and spatial domain with the well-known one
      dimensional linear interpolation strategy. CONCLUSIONS: In conclusion, it is
      recommended to include as much spatial information into the recomputation step as
      possible. This is realized by increasing the dimension of the NFFT. The resulting
      image quality can be enhanced considerably.

PMID- 23127094
TI  - Comparison of a multileaf collimator tracking system and a robotic treatment
      couch tracking system for organ motion compensation during radiotherapy.
AB  - PURPOSE: One limitation of accurate dose delivery in radiotherapy is
      intrafractional movement of the tumor or the entire patient which may lead to an
      underdosage of the target tissue or an overdosage of adjacent organs at risk. In
      order to compensate for this movement, different techniques have been developed.
      In this study the tracking performances of a multileaf collimator (MLC) tracking
      system and a robotic treatment couch tracking system were compared under equal
      conditions. METHODS: MLC tracking was performed using a tracking system based on
      the Siemens 160 MLC. A HexaPOD robotic treatment couch tracking system was also
      installed at the same linac. A programmable 4D motion stage was used to reproduce
      motion trajectories with different target phantoms. Motion localization of the
      target was provided by the 4D tracking system of Calypso Medical Inc. The gained
      positional data served as input signal for the control systems of the MLC and
      HexaPOD tracking systems attempting to compensate for the target motion. The
      geometric and dosimetric accuracy for the tracking of eight different respiratory
      motion trajectories was investigated for both systems. The dosimetric accuracy of
      both systems was also evaluated for the tracking of five prostate motion
      trajectories. RESULTS: For the respiratory motion the average root mean square
      error of all trajectories in y direction was reduced from 4.1 to 2.0 mm for MLC
      tracking and to 2.2 mm for HexaPOD tracking. In x direction it was reduced from
      1.9 to 0.9 mm (MLC) and to 1.0 mm (HexaPOD). The average 2%/2 mm gamma pass rate
      for the respiratory motion trajectories was increased from 76.4% for no tracking
      to 89.8% and 95.3% for the MLC and the HexaPOD tracking systems, respectively.
      For the prostate motion trajectories the average 2%/2 mm gamma pass rate was
      60.1% when no tracking was applied and was improved to 85.0% for MLC tracking and
      95.3% for the HexaPOD tracking system. CONCLUSIONS: Both systems clearly
      increased the geometric and dosimetric accuracy during tracking of respiratory
      motion trajectories. Thereby, the geometric accuracy was increased almost equally
      by both systems, whereas the dosimetric accuracy of the HexaPOD tracking system
      was slightly better for all considered respiratory motion trajectories.
      Substantial improvement of the dosimetric accuracy was also observed during
      tracking of prostate motion trajectories during an intensity-modulated
      radiotherapy plan. Thereby, the HexaPOD tracking system showed better results
      than the MLC tracking.

PMID- 23127096
TI  - Brain necrosis after fractionated radiation therapy: is the halftime for repair
      longer than we thought?
AB  - PURPOSE: To derive a radiobiological model that enables the estimation of brain
      necrosis and spinal cord myelopathy rates for a variety of fractionation schemes,
      and to compare repair effects between brain and spinal cord. METHODS: Sigmoidal
      dose response relationships for brain radiation necrosis and spinal cord
      myelopathy are derived from clinical data using nonlinear regression. Three
      different repair models are considered and the repair halftimes are included as
      regression parameters. RESULTS: For radiation necrosis, a repair halftime of 38.1
      (range 6.9-76) h is found with monoexponential repair, while for spinal cord
      myelopathy, a repair halftime of 4.1 (range 0-8) h is found. The best-fit alpha
      beta ratio is 0.96 (range 0.24-1.73). CONCLUSIONS: A radiobiological model that
      includes repair corrections can describe the clinical data for a variety of
      fraction sizes, fractionation schedules, and total doses. Modeling suggests a
      relatively long repair halftime for brain necrosis. This study suggests that the
      repair halftime for late radiation effects in the brain may be longer than is
      currently thought. If confirmed in future studies, this may lead to a re
      evaluation of radiation fractionation schedules for some CNS diseases,
      particularly for those diseases where fractionated stereotactic radiation therapy
      is used.

PMID- 23127097
TI  - Characterization of lung tumors motion baseline using cone-beam computed
      tomography.
AB  - PURPOSE: To characterize the interfractional variability in lung tumor volume,
      position, and tumor boundaries. METHODS: Cone-beam computed tomography (CBCT)
      scans were acquired weekly during the course of treatment for 34 lung cancer
      patients (1-20 scans) with large tumors. Spatial registration based on bones was
      performed between contoured planning CT and CBCT. Gross tumor volume (GTV) on
      each CBCT was then contoured. Tumor volume, centroid, and boundaries variability
      were quantified. A commercial deformable registration software was tested and
      results were compared to manual contours. RESULTS: Mean volume reduction was 41
      +/- 32% (p < 0.001) after an average time of 51 days. Tumor centroid drifts were
      0.03, 0.14, and -0.13 cm in right-left (RL), anterior-posterior (AP), and
      superior-inferior (SI) directions with standard deviations of 0.55, 0.50, and
      0.51 cm. GTV boundaries displacements were -0.27, -0.14, and -0.16 cm with
      standard deviations of 0.64, 0.57, and 0.59 cm in RL, AP, and SI directions.
      Relative error between deformed and manual contours with the commercial
      deformable registration software rose up exponentially with the GTV decrease.
      CONCLUSIONS: GTV size changes for large lung tumors are similar to those for
      standard tumors. Magnitude absolute values of displacement vector for centroid
      and boundaries shifts show that there is not a preferred direction for the drifts
      but shrinkage.

PMID- 23127098
TI  - Water and tissue equivalence of a new PRESAGE((r)) formulation for 3D proton beam
      dosimetry: a Monte Carlo study.
AB  - PURPOSE: To evaluate the water and tissue equivalence of a new PRESAGE((r)) 3D
      dosimeter for proton therapy. METHODS: The GEANT4 software toolkit was used to
      calculate and compare total dose delivered by a proton beam with mean energy 62
      MeV in a PRESAGE((r)) dosimeter, water, and soft tissue. The dose delivered by
      primary protons and secondary particles was calculated. Depth-dose profiles and
      isodose contours of deposited energy were compared for the materials of interest.
      RESULTS: The proton beam range was found to be ~27 mm for PRESAGE((r)), 29.9 mm
      for soft tissue, and 30.5 mm for water. This can be attributed to the lower
      collisional stopping power of water compared to soft tissue and PRESAGE((r)). The
      difference between total dose delivered in PRESAGE((r)) and total dose delivered
      in water or tissue is less than 2% across the entire water/tissue equivalent
      range of the proton beam. The largest difference between total dose in
      PRESAGE((r)) and total dose in water is 1.4%, while for soft tissue it is 1.8%.
      In both cases, this occurs at the distal end of the beam. Nevertheless, the
      authors find that PRESAGE((r)) dosimeter is overall more tissue-equivalent than
      water-equivalent before the Bragg peak. After the Bragg peak, the differences in
      the depth doses are found to be due to differences in primary proton energy
      deposition; PRESAGE((r)) and soft tissue stop protons more rapidly than water.
      The dose delivered by secondary electrons in the PRESAGE((r)) differs by less
      than 1% from that in soft tissue and water. The contribution of secondary
      particles to the total dose is less than 4% for electrons and ~1% for protons in
      all the materials of interest. CONCLUSIONS: These results demonstrate that the
      new PRESAGE((r)) formula may be considered both a tissue- and water-equivalent 3D
      dosimeter for a 62 MeV proton beam. The results further suggest that tissue
      equivalent thickness may provide better dosimetric and geometric accuracy than
      water-equivalent thickness for 3D dosimetry of this proton beam.

PMID- 23127099
TI  - Metal artifact reduction in computed tomography using local models in an image
      block-iterative scheme.
AB  - PURPOSE: In iterative reconstruction, metal artifacts can be reduced by applying
      more accurate reconstruction models that are usually also more computationally
      demanding. The hypothesis of this work is that these complex models only need to
      be applied in the vicinity of the metals and that a less complex model can be
      used for the remainder of the reconstruction volume. METHODS: A method is
      described that automatically divides the reconstruction volume into metal and
      nonmetal regions. The different regions are called patches. A different energy
      and resolution model can be assigned to each of the patches. The patches
      containing metals are reconstructed with a fully polychromatic spectral model
      (IMPACT) and if necessary with an increased resolution model. The patch without
      metals is reconstructed with a simple polychromatic model (MLTRC) that only
      includes the spectral behavior of water attenuation. Comparing the computational
      complexity of IMPACT and MLTRC gives a ratio of 8:3. The different patches are
      updated sequentially as in a grouped coordinate algorithm. Two phantoms were
      simulated and measured: a circular phantom containing small metal cylinders and a
      body phantom representing a human pelvis with two femoral implants. As a first
      test, the sequential update of the patches was applied while using the same
      energy model for all patches. Second, the local model approach was applied using
      MLTRC for nonmetal regions and IMPACT for metal regions. The results of different
      iterative reconstruction schemes are compared to the results of projection
      completion, another important method for the reduction of metal artifacts.
      RESULTS: Reconstruction schemes including the sequential update of the patches
      result in images with less streak artifacts compared to a regular reconstruction.
      The sequential update of each of the metal regions improves the relative
      convergence of the metals (edges and attenuation values) against the rest of the
      image, which leads to an improved artifact reduction. Using the combined
      IMPACT+MLTRC model results in a similar image quality as using IMPACT everywhere,
      while providing an important benefit regarding computational complexity. Some
      streak and shadow artifacts were still present, but all structures present in the
      phantom could be observed. Projection completion results in reconstructions with
      less obvious streak and shadow artifacts but tends to deform or erase structures
      lying close to or in between metallic structures. CONCLUSIONS: Metal artifact
      reduction with iterative reconstruction can be achieved by using complex models
      only locally without losing image quality. Separately updating metal regions
      leads to reduced streak artifacts. Structures lying close to or in between metals
      are often better reconstructed, compared to projection completion results,
      because all available information is used.

PMID- 23127100
TI  - A clinically feasible method for the detection of potential collision in proton
      therapy.
AB  - PURPOSE: Potential collision between the patient/couch and the gantry could delay
      the start of the treatment and reduce clinical efficiency. The ability to
      accurately detect possible collisions during the treatment planning phase is
      desired. Such collision detection should account for the specific proton gantry
      design, the treatment beam configuration, couch orientation, and the patient
      specific geometry. In this paper the authors developed an approach to detect
      possible patient-machine collisions using patient treatment plan data. METHODS:
      The geometry of the machine and the patient was reconstructed relative to the
      isocenter of the proton treatment room. The surface contour of the gantry was
      first captured from the proton computer aided design and reconstructed to account
      for specific gantry rotation, snout position, collimator rotation, and range
      compensator dimensions based on the patient treatment plan data. The patient body
      and couch contours were captured from the patient's CT DICOM structure file. They
      were reconstructed relative to the isocenter taking into account treatment couch
      rotation. For potential collision that occurs at body portions where no CT images
      exist, scout images are used to construct the body contour. A software program
      was developed using a ray casting algorithm that was applied to detect collisions
      by determining if any of the patient and couch contour points fall into the
      spatial polygons formed by the proton gantry surfaces. RESULTS: Twenty-four
      patient plans with or without potential collisions were retrospectively
      identified and analyzed using the collision detection software. In addition, five
      collision cases were artificially generated using an anthropomorphic phantom. The
      program successfully detected the collisions in all cases. The calculation time
      for each case was within 20 s. The software program was implemented in the
      authors' clinic to detect patient-gantry or gantry-couch collisions in the
      treatment planning phase. CONCLUSIONS: The authors developed a fast and
      clinically feasible patient-specific collision detection program for proton
      therapy based on a ray casting algorithm. If incorporated during the treatment
      planning phase it may lead to improved clinical efficiency. This methodology
      could also be applied to patient collision detection in photon therapy.

PMID- 23127101
TI  - Scintillator high-gain avalanche rushing photoconductor active-matrix flat panel
      imager: zero-spatial frequency x-ray imaging properties of the solid-state SHARP
      sensor structure.
AB  - PURPOSE: The authors are investigating the feasibility of a new type of solid
      state x-ray imaging sensor with programmable avalanche gain: scintillator high
      gain avalanche rushing photoconductor active matrix flat panel imager (SHARP
      AMFPI). The purpose of the present work is to investigate the inherent x-ray
      detection properties of SHARP and demonstrate its wide dynamic range through
      programmable gain. METHODS: A distributed resistive layer (DRL) was developed to
      maintain stable avalanche gain operation in a solid-state HARP. The signal and
      noise properties of the HARP-DRL for optical photon detection were investigated
      as a function of avalanche gain both theoretically and experimentally, and the
      results were compared with HARP tube (with electron beam readout) used in
      previous investigations of zero spatial frequency performance of SHARP. For this
      new investigation, a solid-state SHARP x-ray image sensor was formed by direct
      optical coupling of the HARP-DRL with a structured cesium iodide (CsI)
      scintillator. The x-ray sensitivity of this sensor was measured as a function of
      avalanche gain and the results were compared with the sensitivity of HARP-DRL
      measured optically. The dynamic range of HARP-DRL with variable avalanche gain
      was investigated for the entire exposure range encountered in
      radiography/fluoroscopy (R/F) applications. RESULTS: The signal from HARP-DRL as
      a function of electric field showed stable avalanche gain, and the noise
      associated with the avalanche process agrees well with theory and previous
      measurements from a HARP tube. This result indicates that when coupled with CsI
      for x-ray detection, the additional noise associated with avalanche gain in HARP
      DRL is negligible. The x-ray sensitivity measurements using the SHARP sensor
      produced identical avalanche gain dependence on electric field as the optical
      measurements with HARP-DRL. Adjusting the avalanche multiplication gain in HARP
      DRL enabled a very wide dynamic range which encompassed all clinically relevant
      medical x-ray exposures. CONCLUSIONS: This work demonstrates that the HARP-DRL
      sensor enables the practical implementation of a SHARP solid-state x-ray sensor
      capable of quantum noise limited operation throughout the entire range of
      clinically relevant x-ray exposures. This is an important step toward the
      realization of a SHARP-AMFPI x-ray flat-panel imager.

PMID- 23127102
TI  - Fast parallel algorithms for the x-ray transform and its adjoint.
AB  - PURPOSE: Iterative reconstruction methods often offer better imaging quality and
      allow for reconstructions with lower imaging dose than classical methods in
      computed tomography. However, the computational speed is a major concern for
      these iterative methods, for which the x-ray transform and its adjoint are two
      most time-consuming components. The speed issue becomes even notable for the 3D
      imaging such as cone beam scans or helical scans, since the x-ray transform and
      its adjoint are frequently computed as there is usually not enough computer
      memory to save the corresponding system matrix. The purpose of this paper is to
      optimize the algorithm for computing the x-ray transform and its adjoint, and
      their parallel computation. METHODS: The fast and highly parallelizable
      algorithms for the x-ray transform and its adjoint are proposed for the
      infinitely narrow beam in both 2D and 3D. The extension of these fast algorithms
      to the finite-size beam is proposed in 2D and discussed in 3D. RESULTS: The CPU
      and GPU codes are available at https://sites.google.com/site/fastxraytransform.
      The proposed algorithm is faster than Siddon's algorithm for computing the x-ray
      transform. In particular, the improvement for the parallel computation can be an
      order of magnitude. CONCLUSIONS: The authors have proposed fast and highly
      parallelizable algorithms for the x-ray transform and its adjoint, which are
      extendable for the finite-size beam. The proposed algorithms are suitable for
      parallel computing in the sense that the computational cost per parallel thread
      is O(1).

PMID- 23127103
TI  - Non-Gaussian statistical properties of breast images.
AB  - PURPOSE: Several studies have shown that the power spectrum of x-ray breast
      images is well described by a power-law at lower frequencies where anatomical
      variability dominates. However, an image generated from a Gaussian process with
      this spectrum is easily distinguished from an image of actual breast tissue by
      eye. This demonstrates that higher order non-Gaussian statistical properties of
      mammograms are readily accessible to the visual system. The authors' purpose is
      to quantify and characterize non-Gaussian statistical properties of breast images
      as influenced by processing of a digital mammogram, different imaging modalities,
      and breast density. METHODS: To quantify non-Gaussian statistical properties, the
      authors consider histograms of filter responses from the interior of a breast
      image that have similar properties to receptive fields in the early visual
      system. They quantify departure from a Gaussian distribution by the relative
      entropy of the histogram compared to a best-fit Gaussian distribution. This
      entropy is normalized by the relative entropy of a best-fit Laplacian
      distribution into a measure they refer to as Laplacian fractional entropy (LFE).
      They test the LFE on a set of 26 patients recalled at screening for which they
      have available full-field digital mammography (FFDM), digital breast
      tomosynthesis (DBT), and dedicated breast CT (bCT) images as well as breast
      density scores and biopsy results. RESULTS: A study of LFE in FFDM comparing the
      raw "for-processing" transmission data from the device to log-converted density
      estimates and the processed "for-display" data shows that processing mammographic
      image data enhances the non-Gaussian content of the image. A check of the
      methodology using a Gaussian process with a power-law power spectrum shows
      relatively little bias from the finite extent of the region of interests used. A
      second study comparing LFE across FFDM, DBT, and bCT modalities shows that each
      maximized the non-Gaussian content of the image for different ranges of spatial
      frequency. FFDM is optimal at high spatial frequencies (>0.7 mm(-1)), DBT is
      optimal at mid-range frequencies (0.3-0.7 mm(-1)), and bCT is optimal at low
      spatial frequency (<0.3 mm(-1)). A third study of breast density in FFDM and bCT
      shows that LFE generally rises slightly going from the low-to moderate density,
      and then falls considerably at higher densities. CONCLUSIONS: Non-Gaussian
      statistical structure in breast images that is manifest in the responses of Gabor
      filters similar to receptive fields of the early visual system is dependent on
      how the image data are processed, the modality used to acquire the image, and the
      density of the breast tissue being imaged. Higher LFE corresponds with expected
      improvements from image processing and 3D imaging.

PMID- 23127104
TI  - Automated size-specific CT dose monitoring program: assessing variability in CT
      dose.
AB  - PURPOSE: The potential health risks associated with low levels of ionizing
      radiation have created a movement in the radiology community to optimize computed
      tomography (CT) imaging protocols to use the lowest radiation dose possible
      without compromising the diagnostic usefulness of the images. Despite efforts to
      use appropriate and consistent radiation doses, studies suggest that a great deal
      of variability in radiation dose exists both within and between institutions for
      CT imaging. In this context, the authors have developed an automated size
      specific radiation dose monitoring program for CT and used this program to assess
      variability in size-adjusted effective dose from CT imaging. METHODS: The authors
      radiation dose monitoring program operates on an independent health insurance
      portability and accountability act compliant dosimetry server. Digital imaging
      and communication in medicine routing software is used to isolate dose report
      screen captures and scout images for all incoming CT studies. Effective dose
      conversion factors (k-factors) are determined based on the protocol and optical
      character recognition is used to extract the CT dose index and dose-length
      product. The patient's thickness is obtained by applying an adaptive thresholding
      algorithm to the scout images and is used to calculate the size-adjusted
      effective dose (ED(adj)). The radiation dose monitoring program was used to
      collect data on 6351 CT studies from three scanner models (GE Lightspeed Pro 16,
      GE Lightspeed VCT, and GE Definition CT750 HD) and two institutions over a one
      month period and to analyze the variability in ED(adj) between scanner models and
      across institutions. RESULTS: No significant difference was found between
      computer measurements of patient thickness and observer measurements (p = 0.17),
      and the average difference between the two methods was less than 4%. Applying the
      size correction resulted in ED(adj) that differed by up to 44% from effective
      dose estimates that were not adjusted by patient size. Additionally, considerable
      differences were noted in ED(adj) distributions between scanners, with scanners
      employing iterative reconstruction exhibiting significantly lower ED(adj) (range:
      9%-64%). Finally, a significant difference (up to 59%) in ED(adj) distributions
      was observed between institutions, indicating the potential for dose reduction.
      CONCLUSIONS: The authors developed a robust automated size-specific radiation
      dose monitoring program for CT. Using this program, significant differences in
      ED(adj) were observed between scanner models and across institutions. This new
      dose monitoring program offers a unique tool for improving quality assurance and
      standardization both within and across institutions.

PMID- 23127105
TI  - Emission guided radiation therapy for lung and prostate cancers: a feasibility
      study on a digital patient.
AB  - PURPOSE: Accurate tumor tracking remains a challenge in current radiation
      therapy. Many strategies including image guided radiation therapy alleviate the
      problem to certain extents. The authors propose a new modality called emission
      guided radiation therapy (EGRT) to accurately and directly track the tumor based
      on its biological signature. This work is to demonstrate the feasibility of EGRT
      under two clinical scenarios using a 4D digital patient model. METHODS: EGRT uses
      lines of response (LOR's) from positron emission events to direct beamlets of
      therapeutic radiation through the emission sites inside a tumor. This is
      accomplished by a radiation delivery system consisting of a Linac and positron
      emission tomography (PET) detectors on a fast rotating closed-ring gantry. During
      the treatment of radiotracer-administrated cancer patients, PET detectors collect
      LOR's from tumor uptake sites and the Linac responds in nearly real-time with
      beamlets of radiation along the same LOR paths. Moving tumors are therefore
      treated with a high targeting accuracy. Based on the EGRT concept, the authors
      design a treatment method with additional modulation algorithms including
      attenuation correction and an integrated boost scheme. Performance is evaluated
      using simulations of a lung tumor case with 3D motion and a prostate tumor case
      with setup errors. The emission process is simulated by Geant4 Application for
      Tomographic Emission package (GATE) and Linac dose delivery is simulated using a
      voxel-based Monte Carlo algorithm (VMC++). RESULTS: In the lung case with
      attenuation correction, compared to a conventional helical treatment, EGRT
      achieves a 41% relative increase in dose to 95% of the gross tumor volume (GTV)
      and a 55% increase to 50% of the GTV. All dose distributions are normalized for
      the same dose to the lung. In the prostate case with the integrated boost and no
      setup error, EGRT yields a 19% and 55% relative dose increase to 95% and 50% of
      the GTV, respectively, when all methods are normalized for the same dose to the
      rectum. In the prostate case with integrated boost where setup error is present,
      EGRT contributes a 21% and 52% relative dose increase to 95% and 50% of the GTV,
      respectively. CONCLUSIONS: As a new radiation therapy modality with inherent
      tumor tracking, EGRT has the potential to substantially improve targeting in
      radiation therapy in the presence of intrafractional and interfractional motion.

PMID- 23127106
TI  - Quantitative (90)Y image reconstruction in PET.
AB  - PURPOSE: Positron emission tomography (PET) imaging is increasingly used to
      confirm localization of (90)Y microspheres in the treatment of liver cancer. The
      aim of this work was to evaluate the quantification of (90)Y PET data on a
      current generation time-of-flight extended axial field-of-view PET/CT camera.
      METHODS: The International Electrotechnical Commission (IEC) body phantom was
      used to image six spheres of varying diameters containing a high concentration of
      (90)Y solution in a lower concentration background. Multiple PET studies were
      acquired of the phantom over a number of days during decay. The effect of
      reconstruction parameters in OSEM was evaluated both qualitatively and
      quantitatively. Expected values of total phantom activity, hot-sphere, and
      background concentration were compared to measured values from the reconstructed
      data as well as misplaced events in a cold insert. The partial volume effect was
      measured and the effects of time-of-flight during reconstruction on hot contrast
      recovery and background variability were evaluated according to NEMA-NU2-2007
      protocol, and compared to that for (18)F. The method was applied to a patient
      study following radioembolization to estimate actual implanted radioactivity.
      RESULTS: Increasing the number of OSEM iterations visually deteriorated image
      data and resulted in a larger overall difference of hot concentration measures
      when considering both count high and count poor data. The average difference
      between measured and true total activity and background concentration was found
      to be +5% and +5%, respectively. Measured hot-sphere concentration was linear
      across all datasets, and while estimated to be within error of expected values,
      was consistently underestimated by an average of 23%, 12%, and 8%, when using a
      CT-derived, 50% threshold-derived, and 70% threshold-derived volume of interest,
      respectively. Partial volume effects were evident in all but the largest sphere,
      following an expected relationship between object size and recovery coefficient,
      inferior to that of (18)F. Time-of-flight improved contrast of hot-spheres but
      resulted in a deterioration of background variability, following a similar trend
      to that seen with (18)F. The patient data estimated a total implanted activity of
      1643 MBq, compared to the intended dose of 1780 MBq, with a difference most
      likely due to residual and error in the initial dose calibration. CONCLUSIONS:
      Quantitative (90)Y PET with a state-of-the-art PET/CT scanner with time-of-flight
      and standard corrections for photon interactions demonstrates consistent and
      acceptable measures of total activity and radionuclide concentration across a
      range of realistic count statistics. The method is suitable for measuring the
      radioactivity delivered at the time of (90)Y therapy with the potential for
      absorbed dose calculation.

PMID- 23127107
TI  - Penalization of aperture complexity in inversely planned volumetric modulated arc
      therapy.
AB  - PURPOSE: Apertures obtained during volumetric modulated arc therapy (VMAT)
      planning can be small and irregular, resulting in dosimetric inaccuracies during
      delivery. Our purpose is to develop and integrate an aperture-regularization
      objective function into the optimization process for VMAT, and to quantify the
      impact of using this objective function on dose delivery accuracy and optimized
      dose distributions. METHODS: An aperture-based metric ("edge penalty") was
      developed that penalizes complex aperture shapes based on the ratio of MLC side
      edge length and aperture area. To assess the utility of the metric, VMAT plans
      were created for example paraspinal, brain, and liver SBRT cases with and without
      incorporating the edge penalty in the cost function. To investigate the dose
      calculation accuracy, Gafchromic EBT2 film was used to measure the 15 highest
      weighted apertures individually and as a composite from each of two paraspinal
      plans: one with and one without the edge penalty applied. Films were analyzed
      using a triple-channel nonuniformity correction and measurements were compared
      directly to calculations. RESULTS: Apertures generated with the edge penalty were
      larger, more regularly shaped and required up to 30% fewer monitor units than
      those created without the edge penalty. Dose volume histogram analysis showed
      that the changes in doses to targets, organs at risk, and normal tissues were
      negligible. Edge penalty apertures that were measured with film for the
      paraspinal plan showed a notable decrease in the number of pixels disagreeing
      with calculation by more than 10%. For a 5% dose passing criterion, the number of
      pixels passing in the composite dose distributions for the non-edge penalty and
      edge penalty plans were 52% and 96%, respectively. Employing gamma with 3% dose/1
      mm distance criteria resulted in a 79.5% (without penalty)/95.4% (with penalty)
      pass rate for the two plans. Gradient compensation of 3%/1 mm resulted in
      83.3%/96.2% pass rates. CONCLUSIONS: The use of the edge penalty during
      optimization has the potential to markedly improve dose delivery accuracy for
      VMAT plans while still maintaining high quality optimized dose distributions. The
      penalty regularizes aperture shape and improves delivery efficiency.

PMID- 23127108
TI  - Comment on "linearization of dose-response curve of the radiochromic film
      dosimetry system" [Med. Phys. 39(8), 4850-4857 (2012)].

PMID- 23127112
TI  - Insulin resistance and cardiovascular risk factors in women with PCOS who have
      normal glucose tolerance test.
AB  - INTRODUCTION: We aimed to determine the insulin resistance in women with PCOS
      patients who have normal oral glucose tolerance test (OGTT) and to evaluate
      cardiovascular risk by measuring C-reactive protein (CRP) and carotid intimae
      media thickness (CIMT). METHODS: A total of 34 patients and age and body mass
      matched 20 healthy control subjects were included to this prospective study. Both
      of patients and control groups were consisted of normal oral glucose tolerance
      test. Insulin resistance (IR) was estimated using HOMA-IR method. CRP, lipid and
      hormone levels were measured. CIMT was measured by Carotid Artery B-Mode
      ultrasonography. RESULTS: There was no significant difference between patients
      and controls in BMI, and waist circumference, lipid, TSH, LH, FSH, estradiol, and
      prolactin levels. Serum insulin, testosterone, DHEAS, ferritin levels and HOMA
      values were significantly higher in patient group. We found that 64.7% (n =
      22/34) patients with PCOS had insulin resistance. Both of CIMT and CRP levels
      were significantly higher in the PCOS patients had BMI over 25 kg/m2. CRP levels
      was significantly higher in the PCOS patients had waist circumference greater
      than 80 cm. CONCLUSION: We found insulin resistance in the women with PCOS even
      if OGTT was normal. Our data were similar to literature, the women with PCOS have
      increased risk of premature atherosclerosis and metabolic syndrome.

PMID- 23127113
TI  - Molecular evidence for the bi-clonal origin of neuroendocrine tumor derived
      metastases.
AB  - BACKGROUND: Reports on common mutations in neuroendocrine tumors (NET) are rare
      and clonality of NET metastases has not been investigated in this tumor entity
      yet. We selected one NET and the corresponding lymph node and liver metastases as
      well as the derivative cell lines to screen for somatic mutations in the primary
      NET and to track the fate of genetic changes during metastasis and in vitro
      progression. RESULTS: Applying microarray based sequence capture resequencing
      including 4,935 Exons from of 203 cancer-associated genes and high-resolution
      copy number and genotype analysis identified multiple somatic mutations in the
      primary NET, affecting BRCA2, CTNNB1, ERCC5, HNF1A, KIT, MLL, RB1, ROS1, SMAD4,
      and TP53. All mutations were confirmed in the patients' lymph node and liver
      metastasis tissue as well as early cell line passages. In contrast to the tumor
      derived cell line, higher passages of the metastases derived cell lines lacked
      somatic mutations and chromosomal alterations, while expression of the classical
      NET marker serotonin was maintained. CONCLUSION: Our study reveals that both
      metastases have evolved from the same pair of genetically differing NET cell
      clones. In both metastases, the in vivo dominating "mutant" tumor cell clone has
      undergone negative selection in vitro being replaced by the "non-mutant" tumor
      cell population. This is the first report of a bi-clonal origin of NET derived
      metastases, indicating selective advantage of interclonal cooperation during
      metastasis. In addition, this study underscores the importance to monitor cell
      line integrity using high-resolution genome analysis tools.

PMID- 23127114
TI  - Gastric mucosa-associated lymphoid tissue lymphoma resistant to Helicobacter
      pylori eradication: what's the best option?

PMID- 23127115
TI  - The role of interleukin-9 in lymphoma.
AB  - Although much progress has been made in the treatment of lymphomas, the unclear
      molecular etiology limits its further development. Interleukin-9 (IL-9) was
      initially described as a growth factor secreted by activated helper T cells type
      2 (Th2). Various observations have demonstrated its diverse actions in immune and
      inflammatory responses. In recent years, a resurgence of interest in IL-9 has
      been spurred by the expanded identification of its cellular sources and
      biological targets. Also, the determination of its growth-proliferative and anti
      apoptotic activities on multiple transformed cells implies a potential role of
      this cytokine in tumorigenesis. In this article we review the biologic properties
      and signal transduction pathways of IL-9, and furthermore discuss its possible
      role in lymphomagenesis as well as its impact on non-malignant infiltrating cells
      which are characteristic of the tumor microenvironment.

PMID- 23127116
TI  - Screening whole breast ultrasound: an opportunity to move to personalized,
      effective breast cancer screening.

PMID- 23127117
TI  - Incidence, risk factors, and obstetrical outcomes of women with breast cancer in
      pregnancy.
AB  - Breast cancer in pregnancy is a rare condition. The objective of our study was to
      describe the incidence, risk factors, and obstetrical outcomes of breast cancer
      in pregnancy. We conducted a population-based cohort study on 8.8 million births
      using data from the Healthcare Cost and Utilization Project - Nationwide
      Inpatient Sample from 1999-2008. The incidence of breast cancer was calculated
      and logistic regression analysis was used to evaluate the independent effects of
      demographic determinants on the diagnosis of breast cancer and to estimate the
      adjusted effect of breast cancer on obstetrical outcomes. There were 8,826,137
      births in our cohort of which 573 cases of breast cancer were identified for an
      overall 10-year incidence of 6.5 cases per 100,000 births with the incidence
      slightly increasing over the 10-year period. Breast cancer appeared to be more
      common among women >35 years of age, odds ratio (OR)=3.36 (2.84-3.97); women with
      private insurance plans, OR=1.39 (1.10-1.76); and women who delivered in an urban
      teaching hospital, OR=2.10 (1.44-3.06). After adjusting for baseline
      characteristics, women with pregnancy-associated breast cancer were more likely
      to have an induction of labor, OR=2.25 (1.88, 2.70), but similar rates of
      gestational diabetes, preeclampsia, instrumental deliveries, and placental
      abruption. The incidence of breast cancer in pregnancy appears higher than
      previously reported with women over 35 being at greatest risk. Aside from an
      increased risk for induction of labor, women with breast cancer in pregnancy have
      similar obstetrical outcomes.

PMID- 23127118
TI  - Lobular carcinoma of the breast: presentation, histopathological features and
      management of rectal metastasis.

PMID- 23127119
TI  - Access to mental health care in rural communities among women diagnosed with
      breast cancer.

PMID- 23127120
TI  - Breast cancer in sickle cell disease.

PMID- 23127121
TI  - Folate content and composition of vegetables commonly consumed in China.
AB  - Folate deficiency increases the risk of chronic diseases, including neural tube
      defects (NTDs) in infants, megaloblastic anemia, cardiovascular disease, and some
      cancers in adults. China is the most NTDs prevalent area in the world. Folate
      deficiency in China can be reduced by proper supply of fresh leafy green
      vegetables but little is known about the folate content and vitamers in the
      vegetables commonly consumed by Chinese population. The purposes of this study
      were first to analyze most commonly consumed important vegetables that contribute
      to folate intake in the Chinese population and second to estimate the
      significance of selected vegetables as a source of dietary folate intake. Folate
      content and vitamers forms in vegetables were analyzed using a valid liquid
      chromatography method. Monoenzyme treatment was used for leafy green and some
      fruit vegetables, and dienzyme treatment for some root vegetables. Total folate
      content in commonly consumed vegetables ranged from 14.78 to 145.54 MUg/100 g in
      edible portion with an average of 61.99 MUg/100 g. The highest folate content
      (>140 MUg/100 g) was found in pak choi and spinach. Total folate contents in
      leafy vegetables, fruit vegetables, and root vegetables were in the range of
      17.22 to 145.54 MUg/100g, 18.14 to 86.04 MUg/100g, and 14.78 to 75.81 MUg/100g,
      respectively. The considerable variations in folate content were found in
      different types of vegetables commonly consumed by Chinese population. Leafy
      vegetables are a better source of folate than fruit and root vegetables commonly
      consumed by Chinese population. PRACTICAL APPLICATION: Data from this research
      would facilitate to accurately establish the actual folate intake by Chinese
      population. Our folate composition data on vegetables can be incorporated into
      the national food databases. Availability of such data is essential for
      estimating folate intake and defining an optimal level for fortification program
      in China.

PMID- 23127122
TI  - A fed-batch based cultivation mode in Escherichia coli results in improved
      specific activity of a novel chimeric-truncated form of tissue plasminogen
      activator.
AB  - AIMS: A novel chimeric-truncated form of tissue-type plasminogen activator (t-PA)
      with improved fibrin affinity and resistance to PAI was successfully produced in
      CHO expression system during our previous studies. Considering advantages of
      prokaryotic expression systems, the aim in this study was to produce the novel
      protein in Escherichia coli (BL21) strain and compare the protein potency in
      batch and fed-batch processes. METHODS AND RESULTS: The expression cassette for
      the novel t-PA was prepared in pET-28a(+). The E. coli expression procedure was
      compared in traditional batch and newly developed fed batch, EnBase((r)) Flo
      system. The protein was purified in soluble format, and potency results were
      identified using Chromolize t-PA Assay Kit. The fed-batch fermentation mode,
      coupled with a Ni-NTA affinity purification procedure under native condition,
      resulted in higher amounts of soluble protein, and about a 30% of improvement in
      the specific activity of the resulted recombinant protein (46.66 IU mg(-1) )
      compared to traditional batch mode (35.8 IU mg(-1) ). CONCLUSIONS: Considering
      the undeniable advantages of expression in the prokaryotic expression systems
      such as E. coli for recombinant protein production, applying alternative methods
      of cultivation is a promising approach. In this study, fed-batch cultivation
      methods showed the potential to replace miss-folded formats of protein with
      proper folded, soluble form with improved potency. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Escherichia coli expression of recombinant proteins still counts for
      nearly 40% of marketed biopharmaceuticals. The major drawback of this system is
      the lack of appropriate post-translational modifications, which may cause potency
      loss/decline. Therefore, applying alternative methods of cultivation as
      investigated here is a promising approach to overcome potency decrease problem in
      this protein production system.

PMID- 23127123
TI  - Hydrophobic segregation, phase transitions and the anomalous thermodynamics of
      water/methanol mixtures.
AB  - When water and methanol are mixed, the entropy of mixing decreases, whereas
      mixing simple liquids normally leads to an increase in entropy. One speculation
      on the origin of the anomaly involves formation of water icebergs next to the
      hydrophobic methanol group, while more recent theories point to nanoscale
      clustering of methanol molecules. To elucidate the origin of this effect, we
      carried out extensive molecular dynamics calculations on water/methanol mixtures
      ranging from 0 to 100% and applied the 2PT method to extract the entropy and free
      energy changes of each component as a function of concentration. We find that
      water molecules lose at most 1/35 of their liquid entropy in mixtures. Methanol
      molecules, on the other hand, lose 3 times as much entropy as the water
      molecules, and their rotational entropy contains the signature of the entropic
      loss. We find that methanol has a discontinuous specific heat profile in these
      mixtures with a maximum at 40% methanol. These results do not support the iceberg
      model of immobilized waters and instead suggests a molecular mechanism of
      hydrophobic segregation at low methanol concentration where ordering of the
      methanol molecules bury the hydrophobic group away from the water phase. For
      higher methanol concentrations, there is insufficient water to accomplish this
      effect, and the system freely mixes and transitions to one better described as
      water dissolved into methanol.

PMID- 23127124
TI  - Cryptococcus interactions with macrophages: evasion and manipulation of the
      phagosome by a fungal pathogen.
AB  - Cryptococcus is a potentially fatal fungal pathogen and a leading cause of death
      in immunocompromised patients. As an opportunistic and facultative intracellular
      pathogen of humans, Cryptococcus exhibits a complex set of interactions with the
      host immune system in general, and macrophages in particular. Cryptococcus is
      resistant to phagocytosis but is also able to survive and proliferate within the
      mature phagolysosome. It can cause the lysis of host cells, can be transferred
      between macrophages or exit non-lytically via vomocytosis. Efficient phagocytosis
      is reliant on opsonization and Cryptococcus has a number of anti-phagocytic
      strategies including formation of titan cells and a thick polysaccharide capsule.
      Following uptake, phagosome maturation appears to occur normally, but the
      internalized pathogen is able to survive and replicate. Here we review the
      interactions and host manipulation processes that occur within cryptococcal
      infected macrophages and highlight areas for future research.

PMID- 23127125
TI  - Full stereochemical determination of ajudazols A and B by bioinformatics gene
      cluster analysis and total synthesis of ajudazol B by an asymmetric
      ortholithiation strategy.
AB  - The stereochemical determination of the potent respiratory chain inhibitors
      ajudazols A and B and the total synthesis of ajudazol B are reported.
      Configurational assignment was exclusively based on biosynthetic gene cluster
      analysis of both ketoreductase domains for hydroxyl-bearing stereocenters and one
      of the first predictive enoylreductase alignments for methyl-bearing
      stereocenters. The expedient total synthesis resulting in unambiguous proof of
      the predicted stereochemistry involves a short stereoselective approach to the
      challenging isochromanone stereotriad by an innovative asymmetric ortholithiation
      strategy, a modular oxazole formation, and a late-stage Z,Z-selective Suzuki
      coupling.

PMID- 23127126
TI  - Anorectal atresia and variants at predicted regulatory sites in candidate genes.
AB  - Anorectal atresia is a serious birth defect of largely unknown etiology but
      candidate genes have been identified in animal studies and human syndromes.
      Because alterations in the activity of these genes might lead to anorectal
      atresia, we selected 71 common variants predicted to be in transcription factor
      binding sites, CpG windows, splice sites, and miRNA target sites of 25 candidate
      genes, and tested for their association with anorectal atresia. The study
      population comprised 150 anorectal atresia cases and 623 control infants without
      major malformations. Variants predicted to affect transcription factor binding,
      splicing, and DNA methylation in WNT3A, PCSK5, TCF4, MKKS, GLI2, HOXD12, and BMP4
      were associated with anorectal atresia based on a nominal P value < 0.05. The
      GLI2 and BMP4 variants are reported to be moderately associated with gene
      expression changes (Spearman's rank correlation coefficients between -0.260 and
      0.226). We did not find evidence for interaction between maternal pre-pregnancy
      obesity and variants in MKKS, a gene previously associated with obesity, on the
      risk of anorectal atresia. Our results for MKKS support previously suggested
      associations with anorectal malformations. Our findings suggest that more
      research is needed to determine whether altered GLI2 and BMP4 expression is
      important in anorectal atresia in humans.

PMID- 23127127
TI  - A novel series of conferences tackling the hurdles confronting the translation of
      novel cancer immunotherapies.
AB  - While there has been significant progress in advancing novel immune therapies to
      the bedside, much more needs to be done to fully tap into the potential of the
      immune system. It has become increasingly clear that besides practical and
      operational challenges, the heterogeneity of cancer and the limited efficacy
      profile of current immunotherapy platforms are the two main hurdles.
      Nevertheless, the promising clinical data of several approaches point to a
      roadmap that carries the promise to significantly advance cancer immunotherapy. A
      new annual series sponsored by Arrowhead Publishers and Conferences aims at
      bringing together scientific and business leadership from academia and industry,
      to identify, share and discuss most current priorities in research and
      translation of novel immune interventions. This Editorial provides highlights of
      the first event held earlier this year and outlines the focus of the second
      meeting to be held in 2013 that will be dedicated to stem cells and
      immunotherapy.

PMID- 23127128
TI  - Treatment actions and treatment failure: case studies in the response to severe
      childhood febrile illness in Mali.
AB  - BACKGROUND: Appropriate home management of illness is vital to efforts to control
      malaria. The strategy of home management relies on caregivers to recognize
      malaria symptoms, assess severity and promptly seek appropriate care at a health
      facility if necessary. This paper examines the management of severe febrile
      illness (presumed malaria) among children under the age of five in rural
      Koulikoro Region, Mali. METHODS: This research examines in-depth case studies of
      twenty-five households in which a child recently experienced a severe febrile
      illness, as well as key informant interviews and focus group discussions with
      community members. These techniques were used to explore the sequence of
      treatment steps taken during a severe illness episode and the context in which
      decisions were made pertaining to pursing treatments and sources of care, while
      incorporating the perspective and input of the mother as well as the larger
      household. RESULTS: Eighty-one participants were recruited in 25 households
      meeting inclusion criteria. Children's illness episodes involved multiple
      treatment steps, with an average of 4.4 treatment steps per episode (range: 2
      10). For 76% of children, treatment began in the home, but 80% were treated
      outside the home as a second recourse. Most families used both traditional and
      modern treatments, administered either inside the home by family members, or by
      traditional or modern healers. Participants' stated preference was for modern
      care, despite high rates of reported treatment failure (52%, n=12), however,
      traditional treatments were also often deemed appropriate and effective. The most
      commonly cited barrier to seeking care at health facilities was cost, especially
      during the rainy season. Financial constraints often led families to use
      traditional treatments. CONCLUSIONS: Households have few options available to
      them in moments of overlapping health and economic crises. Public health research
      and policy should focus on the reducing barriers that inhibit poor households
      from promptly seeking appropriate health care. Enhancing the quality of care
      provided at community health facilities and supporting mechanisms by which
      treatment failures are quickly identified and addressed can contribute to
      reducing subsequent treatment delays and avoid inappropriate recourse to
      traditional treatments.

PMID- 23127129
TI  - Commentary on Marczinski and colleagues: mixing an energy drink with an alcoholic
      beverage increases motivation for more alcohol in college students.
AB  - BACKGROUND: This commentary discusses the study by Marczinski and colleagues in
      which they used an alcohol priming procedure to examine the effects of an
      alcohol/energy drink mixture on the priming effect. METHODS: The significance of
      the main findings from this study and new avenues of investigation are discussed.
      RESULTS: Using an alcohol priming paradigm, Marczinski and colleagues report that
      an alcohol/energy drink combination (AmED) prolongs the desire-to-drink rating
      compared with alcohol alone. CONCLUSIONS: The results of this laboratory study
      add to the growing body of literature that the intoxicating effects of AmED are
      different than the intoxication by alcohol alone.

PMID- 23127137
TI  - Multiple modes for gatekeeping at fungal cell-to-cell channels.
AB  - Cell-to-cell channels appear to be indispensable for successful multicellular
      organization and arose independently in animals, plants and fungi. Most of the
      fungi obtain nutrients from the environment by growing in an exploratory and
      invasive manner, and this ability depends on multicellular filaments known as
      hyphae. These cells grow by tip extension and can be divided into compartments by
      cell walls that typically retain a central pore that allows intercellular
      transport and cooperation. In the major clade of filamentous Ascomycota,
      integrity of this coenocytic organization is maintained by Woronin body
      organelles, which function as emergency patches of septal pores. In this issue of
      Molecular Microbiology, Bleichrodt and co-workers show that Woronin bodies can
      also form tight reversible associations with the pore and further link this to
      variation in levels of compartmental gene expression. These data define an
      additional modality of Woronin body-dependent gatekeeping. This commentary
      focuses on the implications of this work and the potential role of different
      modes of pore gating in controlling the growth and development of fungal tissues.

PMID- 23127136
TI  - The Omega-loop lid domain of phosphoenolpyruvate carboxykinase is essential for
      catalytic function.
AB  - Phosphoenolpyruvate carboxykinase (PEPCK) is an essential metabolic enzyme
      operating in the gluconeogenesis and glyceroneogenesis pathways. Recent studies
      have demonstrated that the enzyme contains a mobile active site lid domain that
      undergoes a transition between an open, disorded conformation and a closed,
      ordered conformation as the enzyme progresses through the catalytic cycle. The
      understanding of how this mobile domain functions in catalysis is incomplete.
      Previous studies showed that the closure of the lid domain stabilizes the
      reaction intermediate and protects the reactive intermediate from spurious
      protonation and thus contributes to the fidelity of the enzyme. To more fully
      investigate the roles of the lid domain in PEPCK function, we introduced three
      mutations that replaced the 11-residue lid domain with one, two, and three
      glycine residues. Kinetic analysis of the mutant enzymes demonstrates that none
      of the enzyme constructs exhibit any measurable kinetic activity, resulting in a
      decrease in the catalytic parameters of at least 10(6). Structural
      characterization of the mutants in complexes representing the catalytic cycle
      suggests that the inactivity is due to a role for the lid domain in the formation
      of the fully closed state of the enzyme that is required for catalytic function.
      In the absence of the lid domain, the enzyme is unable to achieve the fully
      closed state and is rendered inactive despite possessing all of the residues and
      substrates required for catalytic function. This work demonstrates how enzyme
      catalytic function can be abolished through the alteration of conformational
      equilibria despite all the elements required for chemical conversion of
      substrates to products remaining intact.

PMID- 23127138
TI  - Risk of large oil spills: a statistical analysis in the aftermath of Deepwater
      Horizon.
AB  - The oil spill in the Gulf of Mexico that followed the explosion of the
      exploration platform Deepwater Horizon on 20 April 2010 was the largest
      accidental oil spill so far. In this paper we evaluate the risk of such very
      severe oil spills based on global historical data from our Energy-Related Severe
      Accident Database (ENSAD) and investigate if an accident of this size could have
      been "expected". We also compare the risk of oil spills from such accidents in
      exploration and production to accidental spills from other activities in the oil
      chain (tanker ship transport, pipelines, storage/refinery) and analyze the two
      components of risk, frequency and severity (quantity of oil spilled) separately.
      This detailed analysis reveals the differences in the structure of the risk
      between different spill sources, differences in trends over time and it allows in
      particular assessing the risk of very severe events such as the Deepwater Horizon
      spill. Such top down risk assessment can serve as an important input to decision
      making by complementing bottom up engineering risk assessment and can be combined
      with impact assessment in environmental risk analysis.

PMID- 23127139
TI  - Competition between meiotic and apomictic pathways during ovule and seed
      development results in clonality.
AB  - Meiotic and apomictic reproductive pathways develop simultaneously in facultative
      aposporous species, and compete to form a seed as a final goal. This
      developmental competition was evaluated in tetraploid genotypes of Paspalum
      malacophyllum in order to understand the low level of sexuality in facultative
      apomictic populations. Cyto-embryology on ovules, flow cytometry on seeds and
      progeny tests by DNA fingerprinting were used to measure the relative incidence
      of each meiotic or apomictic pathway along four different stages of the plant's
      life cycle, namely the beginning and end of gametogenesis, seed formation and
      adult offspring. A high variation in the frequencies of sexual and apomictic
      pathways occurred at the first two stages. A trend of radical decline in realized
      sexuality was then observed. Sexual and apomictic seeds were produced, but the
      efficiency of the sexual pathway dropped drastically, and exclusively clonal
      offspring remained. Both reproductive pathways are unstable at the beginning of
      development, and only the apomictic one remains functional. Key factors reducing
      sexuality are the faster growth and parthenogenetic development in the aposporous
      pathway, and an (epi)genetically negative background related to the extensive
      gene de-regulation pattern responsible for apomixis. The effects of inbreeding
      depression during post-fertilization development may further decrease the
      frequency of effective sexuality.

PMID- 23127140
TI  - The seasonal distribution, diel vertical distribution and feeding behavior of
      Paraeuchaeta concinna in the shallow subtropical coastal waters of eastern Hong
      Kong.
AB  - BACKGROUND: Predatory copepods of the family Euchaetidae are widely distributed
      in polar, temperate, subtropical and tropical oceans. Paraeuchaeta concinna is
      the most abundant Euchaetidae in the subtropical coastal seas of Hong Kong and
      southern China. However, compared to Euchaetidae species in temperate and polar
      regions, relatively little information is available on the ecology of P. concinna
      and other Euchaetidae species in the subtropical oceans. This paper provides
      information on the seasonal abundance of P. concinna in the coastal seas of
      eastern Hong Kong. The diel vertical distribution of P. concinna, feeding
      behavior, and predation impact on mesozooplankton in eastern Hong Kong were also
      investigated. RESULTS: P. concinna is most abundant in winter and spring. Their
      abundance decreases shoreward, and densities are generally higher in the open
      waters of eastern Hong Kong than in the inner parts of Mirs Bay and Tolo Harbour.
      P. concinna exhibits both diel vertical migration and diel feeding rhythms in
      Mirs Bay. P. concinna females show strong preference for the copepods of the
      genera Acrocalanus, Paracalanus, and Parvocalanus, and remove ~4% of their
      standing stocks daily. CONCLUSIONS: The low abundance of P. concinna during most
      of the year suggests it is not indigenous to coastal seas of eastern Hong Kong.
      P. concinna performs diel vertical migration, most likely as a strategy to avoid
      visual predation. Gut content analysis showed that Acrocalanus, Paracalanus, and
      Parvocalanus are highly preferred prey of P. concinna. A daily predation impact
      of ~4% of the standing stocks of Acrocalanus, Paracalanus, and Parvocalanus
      suggests that P. concinna may play an important role in regulating the
      populations of these small copepods in Mirs Bay, especially during winter and
      spring.

PMID- 23127141
TI  - Dynamic actin controls polarity induction de novo in protoplasts.
AB  - Cell polarity and axes are central for plant morphogenesis. To study how polarity
      and axes are induced de novo, we investigated protoplasts of tobacco Nicotiana
      tabacum cv. BY-2 expressing fluorescently-tagged cytoskeletal markers. We
      standardized the system to such a degree that we were able to generate
      quantitative data on the temporal patterns of regeneration stages. The synthesis
      of a new cell wall marks the transition to the first stage of regeneration, and
      proceeds after a long preparatory phase within a few minutes. During this
      preparatory phase, the nucleus migrates actively, and cytoplasmic strands remodel
      vigorously. We probed this system for the effect of anti-cytoskeletal compounds,
      inducible bundling of actin, RGD-peptides, and temperature. Suppression of actin
      dynamics at an early stage leads to aberrant tripolar cells, whereas suppression
      of microtubule dynamics produces aberrant sausage-like cells with asymmetric cell
      walls. We integrated these data into a model, where the microtubular cytoskeleton
      conveys positional information between the nucleus and the membrane controlling
      the release or activation of components required for cell wall synthesis. Cell
      wall formation is followed by the induction of a new cell pole requiring dynamic
      actin filaments, and the new cell axis is manifested as elongation growth
      perpendicular to the orientation of the aligned cortical microtubules.

PMID- 23127142
TI  - The impact of regional deprivation and individual socio-economic status on the
      prevalence of Type 2 diabetes in Germany. A pooled analysis of five population
      based studies.
AB  - AIM: Our objective was to test the hypothesis that the prevalence of Type 2
      diabetes increases with increasing regional deprivation even after controlling
      for individual socio-economic status. METHODS: We pooled cross-sectional data
      from five German population-based studies. The data set contained information on
      n = 11,688 study participants (men 50.1%) aged 45-74 years, of whom 1008 people
      had prevalent Type 2 diabetes (men 56.2%). Logistic multilevel regression was
      performed to estimate odds ratios (OR) and 95% confidence intervals (CI) for
      diabetes prevalence. We controlled for sex, age and lifestyle risk factors,
      individual socio-economic status and regional deprivation, based on a new small
      area deprivation measure, the German Index of Multiple Deprivation. RESULTS:
      Adjusted for sex, age, body mass index (BMI), physical activity, smoking status
      and alcohol consumption, the prevalence of Type 2 diabetes showed a stepwise
      increase in risk with increasing area deprivation [OR 1.88 (95% CI 1.16-3.04) in
      quintile 4 and OR 2.14 (95% CI 1.29-3.55) in quintile 5 compared with the least
      deprived quintile 1], even after controlling for individual socio-economic
      status. Focusing on individual socio-economic status alone, the risk of having
      diabetes was significantly higher for low compared with medium or high
      educational level [OR 1.46 (95% CI 1.24-1.71)] and for the lowest compared with
      the highest income group [OR 1.53 (95% CI 1.18-1.99)]. CONCLUSION: Regional
      deprivation plays a significant part in the explanation of diabetes prevalence in
      Germany independently of individual socio-economic status. The results of the
      present study could help to target public health measures in deprived regions.

PMID- 23127143
TI  - Male reproductive system and antioxidants in oxidative stress induced by
      hypobaric hypoxia.
AB  - In Chile, due to the intensive activity developed in confining areas of the Andes
      Mountains ranging in altitude over 4000 asl, there has been an increasing
      intermittent movement of human resources to high altitude conditions. This
      unusual condition, defined as hypobaric hypoxia, affects notoriously in any
      living organism and there shows a series of physiological responses. Studies
      performed in rats under chronic hypobaric hypoxia and intermittent hypobaric
      hypoxia have registered changes in testicular morphology together with loss of
      spermatogenic cells in all stages of spermatogenic cycle. Furthermore, recent
      tests reinforced the existence of an oxidative metabolism in epididymis of rats
      subjected to hypobaric hypoxia due to the increase in the regulator enzyme
      expression of reactive oxygen species (ROS), This increase in the production of
      ROS induced a rise in apoptosis at germinal cell level, leading to a state of
      hypo-spermatogenesis that may jeopardise masculine fertility. Therefore, the
      eventual development of oxidative stress in spermatogenic cells and consequently
      the spermatozoids of workers subjected to high altitude, either chronic or
      intermittent, turns out to be critical when it poses as an imminent risk to the
      viability and quality of the reproductive cells of workers subjected to
      intermittent hypobaric hypoxia.

PMID- 23127145
TI  - Discontinued drugs in 2011: oncology drugs.
AB  - This year's analysis of discontinued drugs in oncology reveals that the trend of
      increasing numbers of candidate drug development terminations seen in recent
      years has continued into 2011. Thirty-seven drugs were dropped from the global
      oncology development pipeline in 2011, significantly more than the 28
      discontinuations reported in 2010. Of note were the number of terminations
      reported for strategic reasons and the striking number of drugs (23) discontinued
      in or at the end of Phase I development. This article provides a summary of those
      drugs discontinued in 2011 and discusses the observations in the context of the
      rapid changes occurring in the way new anticancer drugs are developed.

PMID- 23127144
TI  - Daily stressors and self-reported changes in memory in old age: the mediating
      effects of daily negative affect and cognitive interference.
AB  - This study examined individual differences in exposure to daily stressors and
      self-reported changes in memory among older adults. A sample of 87 older adults
      completed measures of daily stressful experiences, negative affect (NA),
      cognitive interference (CI), and rated their memory compared to six months ago.
      Results indicated that more frequent exposure to daily stressors was associated
      with rating one's memory to be worse compared to six months prior. Furthermore,
      CI, but not NA partially mediated this association. The findings highlight CI as
      a psychological pathway for understanding the links between daily stress and
      perceptions of memory and cognition in old age.

PMID- 23127146
TI  - Is polycystic ovary syndrome, a state of relative estrogen excess, a real risk
      factor for estrogen-dependant malignancies?
AB  - Polycystic ovary syndrome (PCOS) is a common endocrinopathy affecting women of
      fertile age. It is associated with several risk factors and long-term health
      consequences. Chronic anovulation combined with relative estrogen excess and
      consequent prolonged stimulatory effect on the endometrium can lead to the
      pathogenesis of hormonal dependant carcinoma. PCOS is thus traditionally reported
      to be associated with increased risk of endometrial, as well as breast and
      ovarian cancers. This article provides a critical literature review of the
      relationship between PCOS and the incidence of estrogen-dependant gynecological
      tumours, and it then discusses whether the commonly cited risk factor association
      can be substantiated by high quality studies which comply with the requirements
      of "evidence-based medicine."

PMID- 23127147
TI  - Chronic obstructive pulmonary disease: prevalence, characteristics, and
      pharmacologic treatment in nursing home residents with cognitive impairment.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is prevalent in nursing
      home residents. National and international guidelines exist for management of
      COPD; however, little is known about "real-world" management of COPD in this
      population. Nursing home patients with significant cognitive impairment may have
      difficulty utilizing handheld device (HHD) formulations of respiratory
      medications and may be clinically appropriate candidates for nebulized therapy.
      OBJECTIVES: To determine (a) the prevalence, clinical characteristics, and
      treatment of patients with a diagnosis of "emphysema/COPD" per Minimum Data Set
      (MDS) version 2.0 records in U.S. nursing homes and (b) the relationship of
      nebulized versus HHD formulations of medication to prevalence of shortness of
      breath in a cohort of cognitively impaired nursing home residents. METHODS: In a
      descriptive, retrospective analysis of a large data repository of skilled nursing
      home residents with COPD, prescription claims and MDS data from October 1, 2009,
      through September 30, 2010, were extracted, linked, and de-identified. Measures
      included medications, diagnoses, and selected outcome parameters from the MDS.
      Cognitive impairment was defined as a score of 3-6 on the Cognitive Performance
      Scale derived from MDS records. A proxy of <= 14-day courses of respiratory
      antibiotics, oral corticosteroids, or both was used to identify COPD
      exacerbations. Shortness of breath (SOB) in the last 7 days was captured from
      Section J1.l. of the MDS. RESULTS: The total number of unique patients with at
      least 1 MDS record during the study period was 126,121. Of those, 27,106 (21.5%)
      had COPD. The prevalence rates of diagnoses concurrent with COPD were as follows:
      asthma = 8.6%, Alzheimer's disease or other dementia = 37.2%, congestive heart
      failure = 37.5%, anxiety disorder = 23%, depression = 50.1%, pneumonia = 21.2%,
      and respiratory infection = 9%. 58% of patients with COPD were white females aged
      75 years or older. According to the MDS, 62% of COPD patients had a short-term
      memory problem, while 43.3% of patients had moderately or severely impaired
      cognitive skills for daily decision making. 83% of COPD patients with pharmacy
      claims (17,395/27,106) received at least 1 medication used to treat COPD; 9,711
      (17.1%) received no respiratory medications. Use of beta-agonists (53.9%),
      anticholinergic medications (41.2%), long-acting beta-agonist/corticosteroid
      (LABA/ICS) combinations (28%) in HHD, and nebulized beta-agonist/anticholinergic
      combinations (26.6%) was prevalent. Inhaled LABA/ICS and long-acting
      anticholinergic therapy was received by 28% and 22% residents, respectively. 22%
      (n = 5,085) of patients exhibited at least 2 exacerbations of COPD, and 33% were
      noted to have SOB. Monotherapy with short-acting beta-agonists (SABA) was evident
      in 48.7% of cognitively impaired COPD patients. SOB within the previous 7 days
      was noted in 39.1% of cognitively impaired COPD patients treated with nebulized
      SABA monotherapy. 38% of these patients exhibited 2 or more COPD exacerbations,
      and 57.9% were hospitalized at least once during the 12-month period. LABA
      monotherapy or combined LABA/SABA use represented <= 1% of beta-agonist use for
      unique COPD patients with cognitive impairment. CONCLUSIONS: In this
      retrospective analysis of administrative data, 21.5% of nursing home residents
      had a diagnosis of COPD, and 17% of these residents received no respiratory
      medications. These residents had significant cognitive and functional impairment
      and concurrent diagnoses. 22% of residents experienced at least 2 exacerbations
      of COPD during the 12 months of study. As many as 60% were not receiving inhaled
      LABA/ICS or inhaled tiotropium, and 33% exhibited SOB. There is significant use
      of nebulized SABA monotherapy, which may be contributing to SOB and exacerbations
      or hospitalizations in nursing home residents with COPD.

PMID- 23127148
TI  - Prescribing trends for the outpatient treatment of adolescents and young adults
      with type 2 diabetes mellitus.
AB  - BACKGROUND: Little is known about U.S. outpatient prescribing trends for type 2
      diabetes (T2DM) in adolescents and young adults. OBJECTIVES: To determine (a)
      trends in the outpatient prescribing of pharmacological and nonpharmacological
      therapies and (b) factors influencing prescribing trends for adolescents and
      young adults with T2DM. METHODS: A retrospective, cross-sectional analysis was
      conducted on office visits of adolescents (12-17 years) and young adults (18-39
      years) with T2DM or impaired glucose tolerance (IGT), using the National
      Ambulatory Medical Care Survey (NAMCS) from 1996-2005. Logistic regression was
      used to test for prescribing trends over time. RESULTS: There were an estimated
      1.6 million (93.7% T2DM; 4.4% T2DM + IGT; 1.9% IGT) and 22.2 million (88.1% T2DM;
      11.9% IGT) office visits for adolescents (0.4% of all adolescent visits) and
      young adults (1.2% of all young adult visits) associated with T2DM based on ICD-9
      CM codes, respectively. In young adults, diabetes drug mentions increased
      significantly from 39% of visits with T2DM to 61% in 2004-2005 (P = 0.04). Oral
      diabetes medication mentions increased from 20% to 49% (P = 0.001). However,
      reports of nonpharmacological therapy decreased from 53% in 1996-1997 to 37% in
      2004-2005 (P = 0.14). CONCLUSIONS: The prescribing of pharmacological treatment
      for T2DM increased with emphasis on oral agents, while reports of
      nonpharmacological therapy for T2DM decreased over the 9-year study period with
      increased use of oral medications in both adolescents and young adults. Health
      care providers should consistently consider both treatment approaches when
      prescribing patient care as recommended by treatment guidelines.

PMID- 23127149
TI  - Economic study on the impact of side effects in patients taking oxycodone
      controlled-release for noncancer pain.
AB  - BACKGROUND: Chronic pain is a prevalent condition in the United States.
      Musculoskeletal pain, including joint and back pain, is the most common type of
      chronic pain, and many patients with back pain have a neuropathic component. Pain
      has direct economic consequences. While oxycodone controlled-release (CR) is one
      of the most widely used oral long-acting opioids for pain, including pain with a
      neuropathic component, it is often associated with bothersome side effects,
      resulting in additional medical resource use (MRU) and costs. OBJECTIVE: To
      examine the impact on MRU and costs to payers of side effects in patients taking
      oxycodone CR alone or in combination with other pain medications for noncancer
      pain (including those with neuropathic pain symptoms). METHODS: A nationwide
      convenience sample of adults in the United States, who participated in a survey
      research panel and reported current use of oxycodone CR for noncancer pain,
      completed an online survey between November 2, 2010, and December 13, 2010.
      Respondents were excluded if they reported current use of other extended-release
      or long-acting opioid prescription medications. The survey consisted of questions
      on demographics, clinical characteristics, pain characteristics, experience with
      pain medication, and MRU associated with side effects. Payer costs were
      calculated based on the MRU reported by the respondents multiplied by Medicare
      reimbursement rates for hospitalizations and outpatient visits and average
      wholesale price (AWP) minus 20% for medications. A subgroup of patients who
      reported neuropathic pain symptoms also was examined. RESULTS: After applying the
      exclusion criteria, 432 respondents completed the survey. Approximately half of
      the respondents (n = 219; 50.7%) reported neuropathic pain symptoms. The majority
      of respondents were Caucasian (88.4%) and female (63.7%) with an average age of
      41.8 years (14.89). Respondents most frequently reported low back pain (41.2%),
      followed by osteoarthritis/rheumatoid arthritis (20.4%), neuropathic pain
      (10.6%), and fibromyalgia (9.0%). Respondents reported having their pain
      condition for an average of 5.4 (7.42) years. On days when taken, respondents
      reported a mean oxycodone CR daily dose of 83.3 mg (126.93) taken in an average
      of 2 doses. Most respondents (82.4%) reported experiencing at least 1 side effect
      with 77.5% being bothered by at least 1 side effect. The most frequently reported
      side effects ( greater than 25%) were drowsiness (41.4%), constipation (37.0%),
      fatigue or daytime sleepiness (36.6%), and dizziness (27.1%). Among respondents
      who reported being bothered by one or more side effects in the previous month,
      MRU associated with side effects was reported by 39.1% of respondents and
      significantly increased as the level of side-effect bother increased from 19.8%
      among those "A little bit bothered" to 38.4% among those "Bothered" to 61.0%
      among those "Extremely bothered" (P less than 0.001). Additionally, total average
      payer costs (in 2010 dollars) per respondent in the previous month associated
      with side effects were $238 ($1,159) and also significantly increased as the
      level of side-effect bother increased from $61 ($512) among those "A little bit
      bothered" to $238 ($1,160) among those "Bothered" to $425 ($1,561) among those
      "Extremely bothered" (P less than 0.001). Results reported in the neuropathic
      pain subgroup were similar to results reported in the total study sample.
      CONCLUSIONS: Among adults taking oxycodone CR for chronic noncancer pain (with or
      without a neuropathic pain component), over three-fourths reported being bothered
      by side effects. Respondents who reported higher levels of side-effect bother
      also reported greater MRU, resulting in increased payer costs. The results of
      this study provide further support of the econo-mic burden to payers associated
      with opioid-related side effects in patients with chronic noncancer pain, with
      and without neuropathic pain.

PMID- 23127150
TI  - Improving the success of mailed letter intervention programs to influence
      prescribing behaviors: a review.
AB  - BACKGROUND: Educational interventions have long been used as a means of
      influencing prescribing behavior. Various techniques including educational
      mailings, academic detailing, prescriber feedback with or without disclosing
      patient-identifying data, and supplemental patient information have been used to
      promote appropriate prescribing habits, reduce costs, and optimize patient care.
      While the effects of educational intervention programs are widely reported,
      little information is available regarding the effectiveness of various mailed
      intervention techniques. OBJECTIVE: To review the effectiveness of mailed
      intervention programs and identify factors that may promote successful outcomes.
      METHODS: A literature search was conducted via PubMed for reports of mailed
      intervention programs published through May 2012. Specific search terms included
      "drug utilization review," "drug utilization," "Medicaid," "prescribing
      feedback," "mailed physician intervention," and "mailed physician
      communications." Identified publications that met the following criteria were
      selected for inclusion: (a) evaluated printed educational materials disseminated
      via postal mail, (b) occurred in an outpatient setting, and (c) measured
      intervention impact on prescribing patterns, health care utilization, or economic
      outcomes. Publications that met all 3 criteria were abstracted for intervention
      strategy, follow-up period, data source, intervention target, prescriber
      acceptance of intervention, and effect on prescribing patterns, health care
      utilization, and economic outcomes. RESULTS: A total of 40 published reports
      regarding 39 unique interventions met inclusion criteria. The majority (34/39
      [87.2%]) of studies were conducted in state or federally funded programs; only 5
      programs involved private insurers. All programs used follow-up periods of <=12
      months after final intervention mailing. A total of 26 of the 39 unique
      interventions reported a positive impact on at least 1 target outcome. Programs
      that included a second recipient such as pharmacists (n = 4) reported a greater
      impact as compared with interventions mailed to prescribers alone. Programs that
      provided patient-identifying data had a higher success rate than those that
      supplied prescriber feedback and/or educational materials (21/25 [84.0%] vs. 5/14
      [35.7%]); it should be noted that 2 of the 5 successful programs that provided
      nonpatient-identifying materials also used academic detailing. Programs that sent
      education material and/or prescriber feedback pertaining to multiple medication
      classes or disease states had minimal impact on prescribing patterns (n = 4).
      However, targeting 1 specific disease or medication supported by appropriate
      evidence resulted in favorable change in a short period of time. Additionally,
      providing recommendations that were supported by widely accepted clinical
      guidelines or literature were also associated with a high rate of success. A
      subset of programs that sought to evaluate health care utilization (n=5) and
      economic impact (n = 9) observed little change in measured outcomes. Evaluation
      of prescriber response forms conducted by 7 programs revealed that changes in
      therapy occurred in approximately 50% of patients with prescribers who intended
      to accept intervention recommendations. CONCLUSIONS: Though the degree of
      heterogeneity between articles prevents provision of definite results, it appears
      that a well-constructed mailed intervention program has the potential to evoke
      significant changes in prescribing patterns. Prescribers appear to be receptive
      to mailed interventions; however, there are limited data to determine the
      association between acceptance and actual prescribing change. Future research
      should focus on identifying barriers that may prohibit acceptance of
      recommendations from translating into changes in therapy. Additionally, future
      projects should include longer assessment periods to determine the duration of
      impact following final intervention mailing and potential effect on health care
      and economic outcomes.

PMID- 23127151
TI  - Excess medicaid payments and the stock prices of drug companies.

PMID- 23127152
TI  - Efficient assembly and annotation of the transcriptome of catfish by RNA-Seq
      analysis of a doubled haploid homozygote.
AB  - BACKGROUND: Upon the completion of whole genome sequencing, thorough genome
      annotation that associates genome sequences with biological meanings is
      essential. Genome annotation depends on the availability of transcript
      information as well as orthology information. In teleost fish, genome annotation
      is seriously hindered by genome duplication. Because of gene duplications, one
      cannot establish orthologies simply by homology comparisons. Rather intense
      phylogenetic analysis or structural analysis of orthologies is required for the
      identification of genes. To conduct phylogenetic analysis and orthology analysis,
      full-length transcripts are essential. Generation of large numbers of full-length
      transcripts using traditional transcript sequencing is very difficult and
      extremely costly. RESULTS: In this work, we took advantage of a doubled haploid
      catfish, which has two sets of identical chromosomes and in theory there should
      be no allelic variations. As such, transcript sequences generated from next
      generation sequencing can be favorably assembled into full-length transcripts.
      Deep sequencing of the doubled haploid channel catfish transcriptome was
      performed using Illumina HiSeq 2000 platform, yielding over 300 million high
      quality trimmed reads totaling 27 Gbp. Assembly of these reads generated 370,798
      non-redundant transcript-derived contigs. Functional annotation of the assembly
      allowed identification of 25,144 unique protein-encoding genes. A total of 2,659
      unique genes were identified as putative duplicated genes in the catfish genome
      because the assembly of the corresponding transcripts harbored PSVs or MSVs (in
      the form of pseudo-SNPs in the assembly). Of the 25,144 contigs with unique
      protein hits, around 20,000 contigs matched 50% length of reference proteins, and
      over 14,000 transcripts were identified as full-length with complete open reading
      frames. The characterization of consensus sequences surrounding start codon and
      the stop codon confirmed the correct assembly of the full-length transcripts.
      CONCLUSIONS: The large set of transcripts assembled in this study is the most
      comprehensive set of genome resources ever developed from catfish, which will
      provide the much needed resources for functional genome research in catfish,
      serving as a reference transcriptome for genome annotation, analysis of gene
      duplication, gene family structures, and digital gene expression analysis. The
      putative set of duplicated genes provide a starting point for genome scale
      analysis of gene duplication in the catfish genome, and should be a valuable
      resource for comparative genome analysis, genome evolution, and genome function
      studies.

PMID- 23127153
TI  - Reflectance confocal microscopy for the diagnosis of vulvar melanoma and
      melanosis: preliminary results.
AB  - BACKGROUND: In the early stages, vulvar melanoma can mimic vulvar melanosis and
      therefore the diagnosis is often late and carries a poor prognosis. In vivo
      reflectance-mode confocal microscopy (RCM) is an emerging technique that allows
      noninvasive high-resolution imaging of the skin and mucosa, but it has not been
      employed in the study of genital pigmentation. OBJECTIVE: To analyze the
      characteristics of vulvar melanosis and vulvar melanoma using RCM to define the
      confocal aspects that allow a correct differential diagnosis. METHODS AND
      MATERIALS: Features of eight melanoses and two melanomas of the vulva were
      analyzed using RCM. RCM diagnosis was then compared with clinical and histologic
      diagnosis. RESULTS: Two major characteristics are associated with vulvar
      melanosis: papillae rimmed by bright monomorphous cells and possible presence of
      a few dendritic bright cells in the basal layer of the epithelium. Two major
      features of vulvar melanoma have been identified: atypical cells in the
      epithelium and loss of normal architecture of chorion papillae. CONCLUSIONS:
      Reflectance Confocal Microscopy can play a role in noninvasive differentiation
      between vulvar melanoma and vulvar melanosis, but further broader studies are
      needed to validate our observations.

PMID- 23127155
TI  - Enhanced apoptotic effect of curcumin loaded solid lipid nanoparticles.
AB  - Curcumin is reported to show potent in vitro anticancer effects in a surfeit of
      human cancer cell lines and majorly in the carcinogenesis of GIT, in animals. Its
      poor pharmacokinetics and stability limit its vivo clinical efficacy for the
      other systemic cancers. We recently reported on a 32-155 times enhancement in
      bioavailability of curcumin when incorporated into solid lipid nanoparticles (C
      SLNs). Presently we report on a 54-85% reduction in IC 50 values with developed C
      SLNs in comparison to free curcumin against a panel of human cancer cell lines
      (HL-60, A549, and PC3). Results demonstrate mechanisms similar to those claimed
      for free curcumin, including induction of cellular apoptosis by activation of
      caspases, release of cyctochrome c, loss of membrane potential, blockade of
      nuclear factor kappa B (NF-kappaB) activation, and upregulation of TNF-R for C
      SLNs. However, the extent of cell death provided by C-SLNs in all these tests was
      significantly higher (p < 0.001). This may be attributed to the presentation of
      curcumin in a dispersible/soluble form which enhanced permeability across the
      cell surface. The display of significantly better in vitro anticancer effect
      coupled with high in vivo bioavailability points toward a great potential of
      using C-SLNs for cancer therapeutics. 

PMID- 23127156
TI  - Aggregation behavior of Triton X-100 with a mixture of two room-temperature ionic
      liquids: can we identify the mutual penetration of ionic liquids in ionic liquid
      containing micellar aggregates?
AB  - In this manuscript, we have characterized two different micellar aggregates
      containing all nonvolatile components. We have shown (i) the effect of
      ethylammonium nitrate (EAN) addition on the properties of micellar solution of
      Triton X-100 in 1-butyl-3-methylimidazolium hexafluorophosphate (bmimPF(6)) and
      (ii) the effect of bmimPF(6) addition on the properties of micellar solution of
      Triton X-100 in EAN. To investigate the effect, we have used (1)H NMR, pulsed
      field gradient spin-echo NMR (PFGSE NMR), and methyl orange (MO) and coumarin 153
      (C-153) as absorption and emission probes, respectively. The penetration of added
      EAN inside the Triton X-100/bmimPF(6) micellar aggregates is indicated by (i) red
      shift in both the absorption spectra of MO and emission spectra of C-153 and (ii)
      downfield shift of proton signals of ethylene oxide units in Triton X-100. On the
      other hand, (1)H NMR and PFGSE NMR indicates the penetration of added bmimPF(6)
      inside the Triton X-100/EAN micellar aggregates. However, the constancy of both
      the absorption spectra of MO and emission spectra of C-153 indicates that the
      microenvironment around the probe molecules remains unaffected. We have also
      investigated the effect of micelle formation and the effect of penetration of
      ionic liquids (ILs) in micellar aggregates, on the solvation dynamics of C-153.
      The solvent relaxation around C-153 gets retarded on going from neat ILs to the
      micellar solution of Triton X-100 in ILs. In addition to this, we have also
      observed that with the addition of EAN in Triton X-100/bmimPF(6) micellar
      aggregates the solvation dynamics becomes faster, whereas with the addition of
      bmimPF(6) in Triton X-100/EAN micellar aggregates we did not observe any notable
      change in solvation dynamics. This observation further supports the conclusions
      drawn from UV-visible and NMR studies.

PMID- 23127154
TI  - Presentation of phagocytosed antigens by MHC class I and II.
AB  - Phagocytosis provides innate immune cells with a mechanism to take up and destroy
      pathogenic bacteria, apoptotic cells and other large particles. In some cases,
      however, peptide antigens from these particles are preserved for presentation in
      association with major histocompatibility complex (MHC) class I or class II
      molecules in order to stimulate antigen-specific T cells. Processing and
      presentation of antigens from phagosomes presents a number of distinct challenges
      relative to antigens internalized by other means; while bacterial antigens were
      among the first discovered to be presented to T cells, analyses of the cellular
      mechanisms by which peptides from phagocytosed antigens assemble with MHC
      molecules and by which these complexes are then expressed at the plasma membrane
      have lagged behind those of conventional model soluble antigens. In this review,
      we cover recent advances in our understanding of these processes, including the
      unique cross-presentation of phagocytosed antigens by MHC class I molecules, and
      in their control by signaling modalities in phagocytic cells.

PMID- 23127157
TI  - Polarized photoreflectance and photoluminescence spectroscopy of InGaAs/GaAs
      quantum rods grown with As2 and As4 sources.
AB  - : We report photoreflectance (PR) and photoluminescence (PL) investigations of
      the electronic and polarization properties of different aspect ratio
      (height/diameter) InGaAs quantum rods (QRs) embedded in InGaAs quantum wells
      (QWs). These nanostructures were grown by molecular beam epitaxy using As2or
      As4sources. The impact of the As source on the spectral and polarization features
      of the QR- and QW-related interband transitions was investigated and explained in
      terms of the carrier confinement effects caused by variation of composition
      contrast between the QR material and the surrounding well. Polarized PR and PL
      measurements reveal that the polarization has a preferential direction along the
      [11-0] crystal axis with a large optical anisotropy of about 60% in the (001)
      plane for high aspect ratio (4.1:1) InGaAs QRs. As a result, in PL spectra, the
      transverse magnetic mode dominated (11-0)-cleaved surfaces (TM[001]>TE[110]),
      whereas the transverse electric mode prevailed for (110)-cleaved surfaces
      (TM[001]<TE[110]). This strong optical anisotropy in the (001) plane is
      interpreted in terms of the hole wavefunction orientation along the [11-0]
      direction for high aspect ratio QRs.

PMID- 23127158
TI  - Long-term efficacy of radiofrequency ablation in treatment of common and palmo
      plantar warts.
AB  - Current treatments for warts induce significant local tissue damage and do not
      prevent recurrence. We evaluated the efficacy of localised radiofrequency heat
      (RFH) therapy in inducing the long-term resolution of common and palmo-plantar
      warts in a placebo-controlled randomised single blind trial. Our data show that
      RFH therapy is a safe, cosmetically acceptable and long-term effective treatment
      for warts. 

PMID- 23127159
TI  - Methicillin-resistant Staphylococcus aureus keratitis in a dog.
AB  - The purpose of this study is to report a case of methicillin-resistant
      Staphylococcus aureus (MRSA) keratitis in a dog. A 7-year-old intact male
      American cocker spaniel that had undergone removal of a nictitating gland was
      referred for severe ulcerative keratitis. Slit-lamp examination showed swelling
      of the eyelid, mucopurulent discharge, conjunctival injection and chemosis,
      diffuse corneal edema and opacity, and a deep ulcer in central cornea. Gram
      staining of discharge from the eye demonstrated Gram-positive cocci. Despite
      topical ofloxacin, oxytetracycline and polymyxin B ophthalmic solution and
      intravenous cefazolin, there was no improvement. Cultures revealed MRSA that was
      sensitive only to chloramphenicol, vancomycin, lincomycin, and clindamycin. The
      antibiotic regimen was changed to topical and systemic chloramphenicol. After 9
      days of treatment, although inflammation started to be resolved, the dog
      developed nonregenerative anemia. The antimicrobial regimen was changed again to
      topical and systemic vancomycin. Inflammation continued to improve over the next
      week. MRSA should be considered a potential organism in infectious keratitis,
      especially when general antibiotics are not effective. Although topical and
      systemic chloramphenicol and/or vancomycin are effective for treating MRSA
      keratitis, vancomycin should only be used when culture and susceptibility results
      indicate it is appropriate and no other options are available. To our knowledge,
      this is the first detailed case report of MRSA keratitis in a dog.

PMID- 23127160
TI  - Detection of enterotoxigenic Staphylococcus aureus in raw milk and dairy products
      by multiplex PCR.
AB  - The aim of this study was to investigate the prevalence of enterotoxigenic
      Staphylococcus aureus in 122 samples, including 60 raw milk, 32 white cheese, 10
      kashar cheese, 10 butter, and 10 ice cream samples obtained from Samsun province,
      Turkey. In this study, S. aureus was detected in 64 samples, including raw milk
      (45/60; 75%), white cheese (12/32; 37.5%), kashar cheese (3/10; 30%), butter
      (3/10; 30%), and ice cream (1/10; 10%) samples. A total of 81 isolates were
      identified as S. aureus by PCR with the presence of 16S rRNA and nuc genes. The
      presence of genes encoding the staphylococcal enterotoxins (SEs) SEA, SEB, SEC,
      and SED was detected by multiplex PCR. According to the analysis, seven isolates
      from the raw milk samples (7/51; 13.7%) were enterotoxigenic; five of them
      produced SEA (5/7; 71.4%), one produced SEB (1/7; 14.2%), and one produced
      SEA+SEB (1/7; 14.2%). Four isolates from the white cheese samples (4/21; 19%)
      produced the SEA (1/4; 25%), SEC (1/4; 25%), SED (1/4; 25%), and SEA+SED (1/4;
      25%) toxins. Two isolates from the kashar cheese samples (2/4; 50%) were found to
      be enterotoxigenic; one produced SEA (1/2; 50%) and the other produced SED (1/2;
      50%). One isolate from the butter samples (1/4; 25%) showed enterotoxigenic
      character (SEB, 1/1; 100%). The products were found to be potentially hazardous
      to public health because of the fact that levels of contamination were higher
      than 105-106 cfu/g ml in 39% (25/64, 17 raw milk, 7 white cheese, and 1 butter)
      of the analyzed samples.

PMID- 23127162
TI  - The evolving scenario of copper and fatty liver.

PMID- 23127161
TI  - Serum adiponectin in relation to race-ethnicity and vascular risk factors in the
      Northern Manhattan Study.
AB  - BACKGROUND: Population-based data on serum adiponectin levels, an adipocytokine
      secreted from adipose tissue, are lacking, particularly across race-ethnic
      groups. Studies have suggested an inverse association between adiponectin and
      vascular risk factors, but data are limited and inconsistent. We examined the
      cross-sectional association between adiponectin, vascular risk factors and race
      ethnicity in the population-based Northern Manhattan Study (NOMAS). METHODS:
      Blood samples, anthropomorphics, and vascular risk factors were collected at
      baseline. Multivariable linear regression analysis was conducted with log
      transformed adiponectin as the dependent variable. RESULTS: Adiponectin was
      measured among 2900 participants (age 69+/-10 years, body mass index (BMI) 28.0+/
      5.6, 37% male, 21% white, 53% Hispanic, 24% black). The mean adiponectin was
      11.4+/-6.2 MUg/mL (median=9.8, range=2.1-53.3). After multivariable adjustment,
      adiponectin levels were greatest among whites, followed by Hispanics, and lowest
      among blacks. Lower adiponectin levels were observed in participants with the
      following characteristics: Male, former smoking, hypertension, diabetes,
      homeostasis model assessment of insulin resistance (HOMA-IR), metabolic syndrome,
      moderate alcohol use, elevated waist circumference, BMI, estimated glomerular
      filtration rate (eGFR), triglycerides, low-density lipoprotein cholesterol (LDL
      C), lower high-density lipoprotein cholesterol (HDL-C), and younger age. Obesity
      was a stronger risk factor for decreased adiponectin among blacks than among
      whites or Hispanics. The associations for several vascular risk factors,
      including hypertension, triglycerides, and low HDL-C, with low adiponectin were
      stronger among individuals who were not obese than among those who were obese.
      CONCLUSIONS: Adiponectin levels were lower among blacks and Hispanics and among
      those with various vascular risk factors, and greater with older age. The
      association between BMI and adiponectin varied across race-ethnic groups.
      Investigation of whether differences in body fat distribution may explain race
      ethnic differences in adiponectin is needed.

PMID- 23127163
TI  - Ameliorating effect of lyophilized extract of Butea frondosa leaves on
      scopolamine-induced amnesia in rats.
AB  - CONTEXT: Butea frondosa (BF) Roxb. & Koen. (syn. B. monosperma Lam.) (Fabaceae)
      leaves have been used in folklore medicine for the treatment of diabetes,
      conjunctivitis, gastrointestinal tract, and central nervous system disorders such
      as anxiety, amnesia, etc. OBJECTIVE: To evaluate the effect of lyophilized
      hydroalcoholic extract of BF leaves (BFLE) at 100, 200 and 400 mg/kg, p.o., for
      its memory enhancing activity against scopolamine-induced amnesia in rats.
      MATERIALS AND METHODS: Antiamnesic effect of the BFLE was evaluated using Morris
      water maze and object recognition test models. The effect of BFLE on
      acetylcholinesterase activity and malondialdehyde and glutathione levels were
      also evaluated in brain homogenate. RESULT: BFLE ameliorates scopolamine-induced
      amnesia in both the models with maximum effect at 400 mg/kg. BFLE (400 mg/kg)
      decreased escape latency and increased time spent in target quadrant (24.2 and
      42.5 s, respectively) in comparison to scopolamine (82 and 18.2 s, respectively)
      in the Morris water maze task. In the object recognition test, BFLE produced
      significant increase in ability to discriminate between novel and familiar
      objects. The highest investigated dose of BFLE (400 mg/kg), produced a
      significant decrease in acetylcholinesterase activity and malondialdehyde levels,
      and improves glutathione levels in comparison to scopolamine. Moreover, this
      effect of BFLE at 400 mg/kg was comparable to that of standard, donepezil.
      CONCLUSION: BFLE exhibited significant antiamnesic activity in rats thereby
      validating its folklore use.

PMID- 23127164
TI  - "High" motivation for alcohol: what are the practical effects of energy drinks on
      alcohol priming?
AB  - BACKGROUND: While several researchers have proposed a causal relationship between
      alcohol mixed with energy drink (AmED) consumption and subsequent alcohol intake,
      there is a dearth of research exploring the potential mechanisms underpinning
      this association. METHODS: Marczinski and colleagues (in press) report the
      results of a double-blind, placebo-controlled, between-groups study assessing
      whether an initial AmED dose primes an increased motivation to drink relative to
      alcohol alone. Participants (n = 80) received either alcohol (0.91 ml/kg vodka),
      energy drink (ED; 1.82 ml/kg Red Bull((r)) ), AmED, or a placebo beverage and
      then self-reported their motivation to drink via the Desire-for-Drug scale.
      RESULTS: Subjective ratings of "desire more alcohol" were significantly higher
      than predrink in the placebo, alcohol, and AmED conditions, with this effect
      apparent at more time points in the AmED condition. While it was concluded that
      EDs may increase alcohol priming, between-condition analyses revealed that
      ratings did not differ significantly in AmED and alcohol conditions, with
      moderate magnitude treatment effects at most, and ratings of desire generally
      closer to 0 (absence of desire) than 100 (very much desire). CONCLUSIONS: While
      the study by Marczinski and colleagues fills an important gap in the literature,
      direct measurement of AmED priming's effect on subsequent alcohol consumption
      using a within-subjects design and appropriate statistical comparison is required
      to (i) establish the practical implications of these results for AmED consumers
      and (ii) discount any individual differences in such priming effects.

PMID- 23127165
TI  - Cross-seeding of fibrils from two types of insulin induces new amyloid strains.
AB  - The irreversibility and autocatalytic character of amyloidogenesis and the
      polymorphism of amyloid fibrils underlie the phenomenon of self-propagating
      strains, wherein the mother seed, rather than the seeding environment, determines
      the properties of daughter fibrils. Here we study the formation of amyloid
      fibrils from bovine insulin and the recombinant Lys(B31)-Arg(B32) human insulin
      analog. The two polypeptides are similar enough to cross-seed but, upon
      spontaneous aggregation, form amyloid fibrils with distinct spectral features in
      the infrared amide I' band region. When bovine insulin is cross-seeded with the
      analog amyloid (and vice versa), the shape, absorption maximum, and even fine
      fingerprint features of the amide I' band are passed from the mother to daughter
      fibrils with a high degree of fidelity. Although the differences in primary
      structure between bovine insulin and the Lys(B31)-Arg(B32) analog of human
      insulin lie outside of the polypeptide's critical amyloidogenic regions, they
      affect the secondary structure of fibrils, possibly the formation of
      intermolecular salt bridges, and the susceptibility to dissection and
      denaturation with dimethyl sulfoxide (DMSO). All these phenotypic features of
      mother fibrils are imprinted in daughter amyloid upon cross-seeding. Analysis of
      noncooperative DMSO-induced denaturation of daughter fibrils suggests that the
      self-propagating polymorphism underlying the emergence of new amyloid strains is
      encoded on the level of secondary structure. Our findings have been discussed in
      the context of polymorphism of fibrils, amyloid strains, and possible
      implications for mechanisms of amyloidogenesis.

PMID- 23127166
TI  - Burden of influenza, healthcare seeking behaviour and hygiene measures during the
      A(H1N1)2009 pandemic in France: a population based study.
AB  - BACKGROUND: Influenza surveillance systems do not allow the identification of the
      true burden of illness caused by influenza in the community because they are
      restricted to consulting cases. A study was conducted to estimate the incidence
      and the burden of self-defined influenza, and to describe healthcare seeking
      behavior for self-defined influenza during the A(H1N1)2009 pandemic in the French
      population. METHODS: We conducted a random-based retrospective cross-sectional
      telephone survey between May 2009 and April 2010 among a random sample of the
      French population. RESULTS: For the 10 076 people included, 107 episodes of self
      defined influenza were reported. The annual incidence of self-defined influenza
      was estimated at 13 942 cases per 100 000 inhabitants (CI95% 10 947 - 16 961),
      62.1% (CI95% 50.5 - 72.5) of cases consulted a physician and 11.3% (CI95% 5.5 -
      21.7) used a face mask. Following recommendations, 37.5% (CI95% 35.5 - 39.5) of
      people in the survey reported washing their hands more often during the pandemic
      season, and there was a positive association with being vaccinated against
      A(H1N1)2009 influenza, being a women, being a child (< 15 years) or living in a
      big city (>= 100 000 inhabitants). CONCLUSIONS: Self-defined influenza causes a
      significant burden of illness in the French population and is a frequent cause
      for consultation. These results allow a more accurate interpretation of influenza
      surveillance data and an opportunity to adapt future health education messages.

PMID- 23127167
TI  - Fruit aromas in mature fleshy fruits as signals of readiness for predation and
      seed dispersal.
AB  - The dispersal of seeds away from parent plants seems to be the underlying
      selective force in the evolution of fleshy fruits attractive to animals.
      Secondary metabolites, which are not essential compounds for plant survival, are
      involved in the interaction of fleshy fruits with seed dispersers and
      antagonists. Plant volatile organic compounds (VOCs) are secondary metabolites
      that play important roles in biotic interactions and in abiotic stress responses.
      They are usually accumulated at high levels in specific plant tissues and organs,
      such as fleshy fruits. The study of VOCs emitted during fruit development and
      after different biotic challenges may help to determine the interactions of
      fleshy fruits not only with legitimate vertebrate dispersers, but also with
      insects and microorganisms. A knowledge of fruit VOCs could be used in
      agriculture to generate attraction or repellency to pests and resistance to
      pathogens in fruits. This review provides an examination of specific fruit VOC
      blends as signals for either seed dispersal or predation through simple or
      complex trophic chains, which may also have consequences for an understanding of
      the importance of biodiversity in wild areas.

PMID- 23127168
TI  - The effects of dexketoprofen on duration of analgesia to a thermal stimulus when
      compared with a systemic control in a rat sciatic nerve block with
      levobupivacaine.
AB  - This study was designed to investigate whether dexketoprofen added to perineuraly
      or subcutaneously alters the effects of levobupivacaine in a rat model of sciatic
      nerve blockade. Thirty-six rats received unilateral sciatic nerve blocks along
      with a subcutaneous injection by a blinded investigator assigned at random.
      Combinations were as follows: Group 1 (sham) perineural and subcutaneous saline;
      Group 2, perineural levobupivacaine alone and subcutaneous saline; Group 3,
      perineural levobupivacaine plus dexketoprofen and subcutaneous saline; Group 4,
      perineural levobupivacaine and subcutaneous dexketoprofen; Group 5, perineural
      dexketoprofen and subcutaneous saline; and Group 6, perineural saline and
      subcutaneous dexketoprofen. The levobupivacaine concentration was fixed at 0.05%,
      and the dose of dexketoprofen was 1 mg kg(-1) . Sensory analgesia was assessed by
      paw withdrawal latency to a thermal stimulus every 30 min. The unblocked paw
      served as the control for the assessment of systemic, centrally mediated
      analgesia. Perineural and subcutaneous dexketoprofen coadministered with
      perineural levobupivacaine did not enhance the duration of sensory blockade when
      compared with levobupivacaine alone. There were significant differences between
      the operative and control paws for time points 30-90 min in the perineural
      levobupivacaine alone, levobupivacaine + dexketoprofen and subcutaneous
      dexketoprofen added levobupivacaine group. Significant differences were not
      determined between the levobupivacaine alone group and dexketoprofen added groups
      in operative paw. The effects of dexketoprofen are unknown for perineural
      administration. There is no significant difference between the analgesic effects
      of peripheral nerve blocks using levobupivacaine alone and plus subcutaneous or
      perineural dexketoprofen. 

PMID- 23127170
TI  - Proton transfer in homodimers of carboxylic acids: the rotational spectrum of the
      dimer of acrylic acid.
AB  - The dimer of acrylic acid can exist in two forms, depending on the entgegen or
      zusammen orientations of the two allyl groups. The latter one (zusammen) has a
      permanent value of the MU(b) dipole moment component, which allowed measuring its
      pulsed jet Fourier transform microwave (MW) spectrum. From the tunneling
      splitting, originating in the concerted proton transfer of the two carboxylic
      hydrogen atoms and measured for four isotopologues of such a bimolecule, we could
      determine the barrier and dynamics of the proton transfer.

PMID- 23127169
TI  - Photoactivated disinfection using light-emitting diode as an adjunct in the
      management of chronic periodontitis: a pilot double-blind split-mouth randomized
      clinical trial.
AB  - AIM: This split-mouth double-masked randomized controlled clinical study
      evaluated the effectiveness of photoactivated disinfection (PAD) using light
      emitting diode (LED) as an adjunct in the management of patients affected by
      moderate to severe chronic periodontitis. MATERIALS AND METHODS: Sixteen patients
      affected by moderate to severe chronic periodontitis were enrolled. After scaling
      and root planing (SRP), each quadrant was assigned to one of the following
      groups: LED group (625-635 nm, maximum power density: 2000 mW/cm(2) ),
      photosensitizer group (tolouidine blue O, 0.1 mg/ml), PAD group (photosensitizer
      and LED) and control group (no adjunctive treatment). The adjunctive treatments
      were repeated after 7 and 14 days. The clinical parameters of bleeding on
      probing, probing pocket depth and clinical attachment level were measured at
      baseline and 1 and 3 months after SRP. RESULTS: At 1 and 3 months, all groups
      showed significant improvements with regard to all clinical parameters compared
      to baseline (all p: <0.001). There were no significant differences among groups
      in terms of changes of clinical parameters in any time interval (all p > 0.05).
      CONCLUSION: The application of PAD using LED with the current setting did not
      have additional effects on clinical parameters in patients diagnosed with
      moderate to severe chronic periodontitis compared with SRP alone.

PMID- 23127171
TI  - Understanding Beijing's water challenge: a decomposition analysis of changes in
      Beijing's water footprint between 1997 and 2007.
AB  - Beijing has been experiencing increasing water shortage alongside its astonishing
      economic growth over the past decades. This study conducts a quasi-dynamic input
      output (IO) analysis to investigate changes in Beijing's water footprint (WF) and
      decompose the effects of contributing factors to the changes during 1997-2007.
      The analysis distinguishes "internal" and "external" WF to depict connections of
      Beijing's water use with outside. The results show an increase in Beijing's WF
      from 4342 million m(3) in 1997 to 5748 million m(3) in 2007. Almost all the
      increase was attributable to the expansion of the external WF, while the internal
      WF only changed slightly, indicating a growing dependence of Beijing on external
      water resources. The decomposition analysis reveals that the technological effect
      was the principal contributor to offset the WF increase and the structural effect
      stemmed from the shift of demand toward products of the tertiary industries also
      contributed to reducing the WF. However, these effects were not sufficient to
      reverse the expansion of Beijing's WF resulted from the scale effect induced by
      expansion of final demand and the economic system efficiency effect associated
      with the growth of trade between Beijing and outside. The study provides insights
      into Beijing's water challenge and sheds lights on the combating strategies for
      the future. It is also an endeavor to enhance the policy relevance of the WF
      studies.

PMID- 23127172
TI  - Omega-3 index and prognosis in acute coronary chest pain patients with a low
      dietary intake of omega-3.
AB  - BACKGROUND: The omega-3 index (eicosapentaenoic acid + docosahexaenoic acid)
      content in red blood cell membranes has been suggested as a novel risk marker for
      cardiac death. Objective. To assess the ability of the omega-3 index to predict
      all-cause mortality, cardiac death and sudden cardiac death following
      hospitalization with an acute coronary syndrome (ACS), and to include arachidonic
      acid (AA) in risk assessment. MATERIAL AND METHODS: The omega-3 index was
      measured in 572 consecutive patients (median 63 years and 59% males) admitted
      with chest pain and suspected ACS in an inland Northern Argentinean city with a
      dietary habit that was essentially based on red meat and a low intake of fish.
      Clinical endpoints were collected during a 5-year follow-up period, median 3.6
      years, range 1 day to 5.5 years. Stepwise Cox regression analysis was employed to
      compare the rate of new events in the quartiles of the omega-3 index measured at
      inclusion. Multivariable analysis was performed. RESULTS: No statistical
      significant differences in baseline characteristics were noted between quartiles
      of the omega-3 index. The median of the adjusted omega-3 index was 3.6%. During
      the follow-up period, 100 (17.5%) patients died. Event rates were similar in all
      quartiles of the omega-3 index, with no statistical significant differences. AA
      added no prognostic information. CONCLUSION: In a population with a low intake of
      fish and fish oils, the adjusted omega-3 index did not predict fatal events
      following hospitalization in patients with acute chest pain and suspected ACS.

PMID- 23127173
TI  - Early-age feed restriction affects viability and gene expression of satellite
      cells isolated from the gastrocnemius muscle of broiler chicks.
AB  - BACKGROUND: Muscle growth depends on the fusion of proliferate satellite cells
      to existing myofibers. We reported previously that 0-14 day intermittent feeding
      led to persistent retardation in myofiber hypertrophy. However, how satellite
      cells respond to such nutritional insult has not been adequately elucidated.
      RESULTS: One-day-old broiler chicks were allocated to control (Con, ad libitum
      feeding), intermittent feeding (IF, feed provided on alternate days) and re
      feeding (RF, 2 days ad libitum feeding after 12 days of intermittent feeding)
      groups. Chickens were killed on Day 15 and satellite cells were isolated. When
      cultured, satellite cells from the IF group demonstrated significant retardation
      in proliferation and differentiation potential, while RF partly restored the
      proliferation rate and differentiation potential of the satellite cells.
      Significant up-regulation of insulin like growth factor I receptor (IGF-IR)
      (P<0.05) and thyroid hormone receptor alpha (TRalpha) (P<0.05), and down
      regulation of growth hormone receptor (GHR) (P<0.01) and IGF-I (P<0.01) mRNA
      expression was observed in freshly isolated IF satellite cells when compared with
      Con cells. In RF cells, the mRNA expression of IGF-I was higher (P<0.05) and of
      TRalpha was lower (P<0.01) than in IF cells, suggesting that RF restored the mRNA
      expression of TRalpha and IGF-I, but not of GHR and IGF-IR. The Bax/Bcl-2 ratio
      tended to increase in the IF group, which was reversed in the RF group (P<0.05),
      indicating that RF reduced the pro-apoptotic influence of IF. Moreover, no
      significant effect of T3 was detected on cell survival in IF cells compared with
      Con (P<0.001) or RF (P<0.05) cells. CONCLUSIONS: These data suggest that early
      age feed restriction inhibits the proliferation and differentiation of satellite
      cells, induces changes in mRNA expression of the GH/IGF-I and thyroid hormone
      receptors in satellite cells, as well as blunted sensitivity of satellite cells
      to T3, and that RF partially reverses these effects. Thus, a moderate nutritional
      strategy for feed restriction should be chosen in early chick rearing systems.

PMID- 23127174
TI  - Therapeutic targeting of c-KIT in cancer.
AB  - INTRODUCTION: Mutated forms of the receptor tyrosine kinase c-KIT are "drivers"
      in several cancers and are attractive targets for therapy. While benefits have
      been obtained from use of inhibitors of KIT kinase activity such as imatinib,
      especially in gastrointestinal stromal tumours (GIST), primary resistance occurs
      with certain oncogenic mutations. Furthermore, resistance frequently develops due
      to secondary mutations. Approaches to addressing both of these issues as well as
      combination therapies to optimise use of KIT kinase inhibitors are discussed.
      AREAS COVERED: This review covers the occurrence of oncogenic KIT mutations in
      different cancers and the molecular basis of their action. The action of KIT
      kinase inhibitors, especially imatinib, sunitinib, dasatinib and PKC412, on
      different primary and secondary mutants is discussed. Outcomes of clinical trials
      in GIST, acute myeloid leukaemia (AML), systemic mastocytosis and melanoma and
      their implications for future directions are considered. EXPERT OPINION: Analysis
      of KIT mutations in individual patients is an essential prerequisite to the use
      of kinase inhibitors for therapy, and monitoring for development of secondary
      mutations that confer drug resistance is necessary. However, it is unlikely that
      KIT inhibitors alone can lead to cure. KIT mutations alone do not seem to be
      sufficient for transformation; thus identification and co-targeting of
      synergistic oncogenic pathways should lead to improved outcomes.

PMID- 23127175
TI  - Impact of age and body mass on the intensity of menopausal symptoms in 5968
      Brazilian women.
AB  - OBJECTIVE: To assess the relationship of onset of menopause and body mass on the
      menopausal symptoms in post-menopausal Brazilian women. DESIGN: Observational
      study conducted by the selection and inclusion of 5968 Brazilian women after
      menopause. The following variables were analyzed in this study: time at
      menopause; the relationship between age at menarche and age at menopause;
      vasomotor symptoms compared with age at the time of menopause and the time of
      menopause; Kupperman menopausal index (KMI) versus total time of menopause; body
      mass index (BMI) compared to the time of menopause, vasomotor symptoms, and KMI
      total score. We used the Chi-square test, and the significance level was set at
      5%. RESULTS: The age at natural menopause ranged from 41 to 62 years (mean 48.1
      +/- 4.07 years). A younger age at menopause was associated with a high intensity
      of vasomotor symptoms. These symptoms were more intense in the first 5 years of
      menopause and decreased with time. The KMI total also decreased with time after
      menopause, with the exception of arthralgia, myalgia, and insomnia, which did not
      tend to improve over time. In addition, the vasomotor symptoms and total KMI were
      more frequent with increasing BMI. CONCLUSIONS: Our results suggested that the
      age of menopause and BMI may influence the intensity of vasomotor symptoms.

PMID- 23127181
TI  - Extramammary Paget's disease of the perianal region: a review of the literature
      emphasizing management.
AB  - BACKGROUND: Perianal Paget's disease is a rare malignant condition affecting the
      epidermal apocrine gland that is usually complicated, with a confusing clinical
      picture, and diagnosis is therefore often delayed. Although, more than 100 years
      has gone by since its first description by Darier and Coulillaud in 1893, proper
      treatment guidelines have yet to be established. OBJECTIVE: To review the
      available literature, emphasizing various current treatment strategies and aiming
      to increase clinicians' awareness of this rare disease, along with its
      management, for better practice and improvement of patient prognosis. METHODS:
      The review of the concerned literature was done by searching and compiling data
      available on PubMed, Medline, and other databases using the key words "perianal
      Paget's disease," "extramammary Paget's disease," "intraepithelial
      adenocarcinoma," and "apocrine glands." CONCLUSIONS: Surgery is the mainstay of
      treatment. Some noninvasive therapeutic modalities were also reported to be
      effective, such as photodynamic therapy, imiquimod, radiotherapy, chemotherapy,
      anti-androgen therapy, and carbon dioxide. Management of perianal Paget's disease
      remains difficult, and large controlled, multicentric studies should be performed
      to compare the effectiveness of current therapeutic modalities.

PMID- 23127182
TI  - Further reduction in adenovirus vector-mediated liver transduction without
      largely affecting transgene expression in target organ by exploiting microrna
      mediated regulation and the Cre-loxP recombination system.
AB  - In order to detarget undesirable transduction in the liver by an adenovirus (Ad)
      vector, we previously demonstrated that insertion of sequences perfectly
      complementary to liver-specific miR-122a into the 3'-untranslated region (UTR) of
      transgene specifically reduced the transgene expression in the liver by
      approximately 100-fold; however, a certain level of residual transgene expression
      was still found in the liver. In order to further suppress the hepatic
      transduction, we developed a two-Ad vector system that uses the microRNA (miRNA)
      regulated transgene expression system and the Cre-loxP recombination system,
      i.e., insertion of miR-122a target sequences and loxP sites into the transgene
      expression cassette and coadministration of a Cre recombinase-expressing Ad
      vector. In addition, to maintain as much as possible the transgene expression in
      the spleen, which is the target organ of this study, spleen-specific miR-142-3p
      target sequences were inserted into the 3'-UTR of the Cre recombinase gene to
      suppress Cre recombinase expression in the spleen. The spleen is an attractive
      target for immunotherapy because the spleen plays important roles in the immune
      system. Coadministration of Ad vector possessing CMV promoter-driven Cre
      recombinase expression cassette with miR-142-3p target sequences resulted in a
      further 24-fold reduction in the hepatic transgene expression by the Ad vector
      containing miR-122a target sequences and loxP sites, compared with
      coadministration of control Ad vector. On the other hand, there was no
      significant reduction of transgene expression in the spleen. 

PMID- 23127183
TI  - A model system for assessing and comparing the ability of exon microarray and tag
      sequencing to detect genes specific for malignant B-cells.
AB  - BACKGROUND: Malignant cells in tumours of B-cell origin account for 0.1% to 98%
      of the total cell content, depending on disease entity. Recently, gene expression
      profiles (GEPs) of B-cell lymphomas based on microarray technologies have
      contributed significantly to improved sub-classification and diagnostics.
      However, the varying degrees of malignant B-cell frequencies in analysed samples
      influence the interpretation of the GEPs. Based on emerging next-generation
      sequencing technologies (NGS) like tag sequencing (tag-seq) for GEP, it is
      expected that the detection of mRNA transcripts from malignant B-cells can be
      supplemented. This study provides a quantitative assessment and comparison of the
      ability of microarrays and tag-seq to detect mRNA transcripts from malignant B
      cells. A model system was established by eight serial dilutions of the malignant
      B-cell lymphoma cell line, OCI-Ly8, into the embryonic kidney cell line, HEK293,
      prior to parallel analysis by exon microarrays and tag-seq. RESULTS: We
      identified 123 and 117 differentially expressed genes between pure OCI-Ly8 and
      HEK293 cells by exon microarray and tag-seq, respectively. There were thirty
      genes in common, and of those, most were B-cell specific. Hierarchical clustering
      from all dilutions based on the differentially expressed genes showed that
      neither technology could distinguish between samples with less than 1% malignant
      B-cells from non-B-cells. A novel statistical concept was developed to assess the
      ability to detect single genes for both technologies, and used to demonstrate an
      inverse proportional relationship with the sample purity. Of the 30 common genes,
      the detection capability of a representative set of three B-cell specific genes-
      CD74, HLA-DRA, and BCL6 - was analysed. It was noticed that at least 5%, 13% and
      22% sample purity respectively was required for detection of the three genes by
      exon microarray whereas at least 2%, 4% and 51% percent sample purity of
      malignant B-cells were required for tag-seq detection. CONCLUSION: A sample
      purity-dependent loss of the ability to detect genes for both technologies was
      demonstrated. Taq-seq, in comparison to exon microarray, required slightly less
      malignant B-cells in the samples analysed in order to detect the two most
      abundantly expressed of the selected genes. The results show that malignant cell
      frequency is an important variable, with fundamental impact when interpreting
      GEPs from both technologies.

PMID- 23127184
TI  - Enantiostyly in Chamaecrista ramosa (Fabaceae-Caesalpinioideae): floral
      morphology, pollen transfer dynamics and breeding system.
AB  - Enantiostyly is a form of reciprocal herkogamy, in which floral morphs present
      reciprocal differences in the position of sexual elements, and occurs in
      monomorphic and dimorphic forms. This polymorphism maximises cross-pollination
      and reduces self-pollination, being very common within the subtribe Cassiinae
      (Fabaceae). Nevertheless, few studies have investigated the functionality of
      enantiostyly, particularly in this plant group. The present study aimed to
      investigate enantiostyly and its functionality in Chamaecrista ramosa, a
      monomorphic enantiostylous shrub, in an area of coastal vegetation in northeast
      Brazil. Pollen deposition and capture on the body of floral visitors, the
      relationship of these data with floral biology and breeding system, and morph
      ratio were evaluated. Pollen deposition and capture occurred in specific sites of
      the floral visitor body, showing the functionality of enantiostyly. The floral
      architecture, associated with the floral visitor behaviour, resulted in indirect
      pollen deposition on the floral visitor body. This occurred through a loop made
      by the pollen upon the inner petal surface, similar that generally reported for
      other Cassiinae. Chamaecrista ramosa is self-compatible, although no fruit set
      was observed through spontaneous self-pollination. The occurrence and number of
      floral morphs was similar within clumps. Enantiostyly seems to be advantageous
      for this species, as it results in efficient pollen capture and deposition,
      reduces the chances of autogamy and maximises intermorph pollen flow.

PMID- 23127185
TI  - Gene profiling in partially resistant and susceptible near-isogenic tomatoes in
      response to late blight in the field.
AB  - In order to better understand resistance to Phytophthora infestans in tomato, we
      compared the global gene expression of the susceptible tomato, M82, with its more
      resistant near-isogenic line, 6-2 (IL6-2), under field conditions using a
      microarray with more than 12 800 tomato expressed sequence tags (ESTs). Because
      variance in the field was a major concern, we investigated the likelihood of
      false positives or false negatives and demonstrated that either probability was
      very low. The two isolines had indistinguishable constitutive gene expressions
      prior to inoculation. However, a few genes were particularly prone to variation
      in both isolines in the absence of P. infestans. Included among these genes were
      catalase, genes coding for pathogenesis-related proteins, endochitinase and
      cytochrome P450. In response to inoculation with P. infestans, a time course of
      gene expression identified 1248 transcripts that were similarly induced or
      repressed in each line, and 991 that were differentially expressed between the
      two lines. These differences provide hypotheses to explain the difference in
      resistance between the two isolines. For example, one hypothesis is that genes up
      regulated in IL6-2 in response to inoculation with P. infestans, but not up
      regulated in M82, contribute to the resistance in IL6-2. Using virus-induced gene
      silencing (VIGS), we were able to partially silence two such genes-one encoded a
      protein with homology to an R gene with the Toll/interleukin-1 receptor
      nucleotide-binding site-leucine-rich repeat (TIR-NBS-LRR) motif (37O19) and the
      other encoded a peroxisomal membrane protein (35P7). Partial silencing of 37O19
      reduced the resistance in IL6-2 (P = 0.001), but had no effect on the response of
      M82. Partial silencing of 35P7 reduced the resistance in IL6-2 moderately
      significantly (P = 0.067), but had no effect in M82. We expect that hypotheses
      developed from this gene expression study performed under field conditions will
      provide an important avenue to an accurate understanding of the genes involved in
      resistance.

PMID- 23127186
TI  - Atypical chronic sterile paronychia leading to tissue and joint space destruction
      in a patient with thromboangiitis obliterans.
AB  - We report the case of a patient with severe thromboangiitis obliterans (Buerger's
      disease) and untreated paronychia which eroded into the digital joint space
      causing acrolysis of digits and significant soft tissue and joint destruction. 

PMID- 23127187
TI  - Role of tunneling in the enzyme glutamate mutase.
AB  - The role of quantum mechanical atom tunneling during the conversion of glutamate
      to methylaspartate catalyzed by glutamate mutase is investigated by quantum
      mechanical/molecular mechanical (QM/MM) simulations based on coupled cluster and
      density functional calculations. The use of instanton theory allows us to
      calculate the tunneling contributions of up to 78 atoms in the active site. We
      calculate kinetic isotope effects (KIEs) and compare them to experimental data.
      The simulations lead to deuterium KIEs of 10 for the hydrogen abstraction from
      glutamate substrate and 16 for the hydrogen abstraction from methylaspartate
      substrate, which are consistent with the experimental results. The hydrogen
      abstraction from methylaspartate has higher primary deuterium and tritium (46.1)
      KIEs than the abstraction from glutamate. The tunneling effect increases the
      reaction rate by a factor of 12.3 for the hydrogen abstraction from
      methylaspartate at 0. Tunneling is supported by the environment by preparing the
      enzyme through classical motions. Consideraton of the tunneling contributions of
      more and more atoms around the active center shows that the motions at the ribose
      ring play a central role during the tunneling enhancement of the hydrogen
      transfers. Our simulations give new insight into the catalytic process in
      glutamate mutase and the way enzymes use tunneling effects for a successful
      catalysis.

PMID- 23127188
TI  - Canine Dirofilaria infections in two uninvestigated areas of Serbia:
      epidemiological and genetic aspects.
AB  - In 2009 canine filarial infections were investigated in two northern areas of
      Serbia (Pancevo and Veliko Gradiste), applying morphometry, biochemical staining,
      and immunological kit to detect Dirofilaria immitis antigens, and two home-made
      ELISAs to detect antibodies to D. repens and D. immitis somatic/metabolic
      polyproteins. Moreover, molecular tools were applied to analyze the phylogenetic
      relationships of the isolates. The microfilariae detected in 21/122 dogs (17.2%)
      were identified as D. repens (n=21) and D. immitis (n=2). D. immitis antigens
      were found in another 13 animals with occult infection. All of the 15 heartworm
      positive dogs also had antibodies to this parasite, which were detected in
      another 13 subjects, indicating an overall D. immitis seroprevalence rate of
      22.9%. Serology for D. repens revealed evidence of antibodies in 42.6% of the
      dogs, but was negative for 4 microfilaremic dogs. As for the two different areas,
      the prevalence of microfilariae and/or D. immitis antigens, mainly due to D.
      repens microfilaremic animals, was not significantly higher in Veliko Gradiste
      (33.3%) than in Pancevo (22%). However, serology showed a different
      epidemiological picture. Heartworm infection occurred more often in both areas,
      and antibodies to dirofilarial nematodes were detected in 72.9% of dogs living in
      Pancevo, a rate higher than in those living in Veliko Gradiste (57.1%). No risk
      factors for infection were found, confirming the uselessness of prophylactic
      drugs against D. repens, and suggesting the presence in these areas of sunrise-
      or sunset-biting mosquitoes as important vectors. The results indicate the need
      for both appropriate entomological studies and further research on the intra
      species variability shown by D. repens.

PMID- 23127189
TI  - Southern plains woodrats (Neotoma micropus) from southern Texas are important
      reservoirs of two genotypes of Trypanosoma cruzi and host of a putative novel
      Trypanosoma species.
AB  - Trypanosoma cruzi, the causative agent of Chagas' disease, is an important public
      health and veterinary pathogen. Although human cases are rare in the United
      States, infections in wildlife, and in some areas domestic dogs, are common. In
      2008 and 2010, we investigated T. cruzi prevalence in possible vertebrate
      reservoirs in southern Texas, with an emphasis on southern plains woodrats
      (Neotoma micropus). Infection status was determined using a combination of
      culture isolation, polymerase chain reaction (PCR), and serologic testing. Based
      on PCR and/or culture, T. cruzi was detected in 35 of 104 (34%) woodrats, 3 of 4
      (75%) striped skunks (Mephitis mephitis), 12 of 20 (60%) raccoons (Procyon
      lotor), and 5 of 28 (18%) other rodents including a hispid cotton rat (Sigmodon
      hispidus), rock squirrel (Otospermophilus variegatus), black rat (Rattus rattus),
      and two house mice (Mus musculus). Additionally, another Trypanosoma species was
      detected in 41 woodrats, of which 27 were co-infected with T. cruzi. Genetic
      characterization of T. cruzi revealed that raccoon, rock squirrel, and cotton rat
      isolates were genotype TcIV, while woodrats and skunks were infected with TcI and
      TcIV. Based on the Chagas Stat-Pak assay, antibodies were detected in 27 woodrats
      (26%), 13 raccoons (65%), 4 skunks (100%), and 5 other rodents (18%) (two white
      ankled mice [Peromyscus pectoralis laceianus], two house mice, and a rock
      squirrel). Seroprevalence based on indirect immunofluorescence antibody testing
      was higher for both woodrats (37%) and raccoons (90%), compared with the Chagas
      Stat-Pak. This is the first report of T. cruzi in a hispid cotton rat, black rat,
      rock squirrel, and white-ankled mouse. These data indicate that based on culture
      and PCR testing, the prevalence of T. cruzi in woodrats is comparable with other
      common reservoirs (i.e., raccoons and opossums) in the United States. However,
      unlike raccoons and opossums, which tend to be infected with a particular
      genotype, southern plains woodrats were infected with TcI and TcIV at near equal
      frequencies.

PMID- 23127190
TI  - Decapitation in suicidal hanging--vital reaction patterns.
AB  - Complete or incomplete decapitation as a consequence of suicidal hanging is very
      rare, few cases having been reported in the worldwide literature. Posthanging
      decapitation is typically related to a drop of several meters. Three cases of
      complete decapitation and one case of incomplete decapitation by suicidal hanging
      are reported with particular emphasis on internal findings and vital reaction
      patterns. Personal, circumstantial, autopsy, and toxicological data were analyzed
      to define basic characteristics of such extreme injuries. The crucial factor for
      the state of decapitation itself is the kinetic energy of the falling body, the
      strength of the human neck tissue, and the diameter and elasticity of the used
      ligature. Results of our case study suggest Simon's hemorrhage and air embolism
      as useful autopsy findings in posthanging beheading cases. Simon's hemorrhage was
      demonstrated in three cases of four. The test for air embolism was positive in
      all four cases.

PMID- 23127191
TI  - Visualization and attentive behavior for pain reduction during radiofrequency
      ablation of atrial fibrillation.
AB  - BACKGROUND: Radiofrequency (RF) ablation of atrial fibrillation (AF) can be
      accompanied by pain and anxiety when light conscious sedation is used. We sought
      to determine how visualization and structured attentive behavior during ablation
      of AF could reduce pain intensity, spontaneously expressed pain, the amount of
      analgesics, anxiety, and adverse events. METHODS: A clinical controlled study
      with 71 patients in a control group (CG), receiving conventional care and
      treatment, and 76 patients in an intervention group (IG), receiving relaxation
      and visualization, combined with a structured attentive behavior from staff.
      RESULTS: There was no difference between CG and IG in perception of pain
      intensity at 15-minute intervals; mean pain intensity: CG (0.00-2.90), IG (0.12
      2.57), (NS), but patients spontaneously expressed pain less numbers of time
      outside fixed intervals in the IG: 1.4 +/- 1.2 times (mean +/- standard deviation
      [SD]) compared to CG: 2.8 +/- 1.8 (P < 0.01). There was a statistically
      significant difference between the amount of analgesics (Fentanyl) used in the
      two groups: CG: 292.3 +/- 107 MUg (mean +/- SD) and IG: 220.7 +/- 93 MUg (P <
      0.0001). No effect was observed in perception of anxiety, mean anxiety: CG (0.10
      1.84), IG (0.9-2.03)(NS), and the number of adverse events (P = 0.241).
      CONCLUSION: Visualization and structured attentive behavior was shown to reduce
      the amount of analgesics during the RF ablation of AF. There was no difference in
      perception of pain intensity, but the patients spontaneously expressed pain
      significantly less numbers of times outside the scheduled measurements. There was
      no reduction in anxiety and numbers of adverse events.

PMID- 23127192
TI  - Antioxidant and anti-inflammatory activities of Pittocaulon species from Mexico.
AB  - context: Stems and leaves of Pittocaulon spp. (Asteraceae) are used in Mexican
      traditional medicine as an anti-inflammatory substance and for the treatment of
      skin injuries. OBJECTIVE: This study evaluated the antioxidant activity of
      methanol (MeOH) and dichloromethane (DC) extracts of five Pittocaulon species.
      MATERIALS AND METHODS: DC and MeOH extracts from flowers, roots, and stems of
      Pittocaulon praecox (Cav.) H. Rob. & Brettell, P. bombycophole (Bullock) H. Rob.
      & Brettell, P. filare (Mc Vaugh) H. Rob. & Brettell, P. velatum (Greenm.) Rob. &
      Brettell and P. hintonii H. Rob. & Brettell. RESULT AND DISCUSSION: In the 2,2
      diphenyl-1-picrylhydrazyl (DPPH) assay, the flower extracts obtained with MeOH
      were the most active with IC(50) values ranging from 51.83 +/- 4.08 to 154.19 +/-
      8.39 ppm. In the thiobarbituric acid reactive substances (TBARS) model, the best
      activity was shown by DC extracts of roots with IC(50) values ranging from 55.54
      +/- 1.28 to 160.82 +/- 5.37 ppm. The MeOH extract of flowers of P. bombycophole
      had the highest IC(50) value in both DPPH (51.83 +/- 4.08 ppm) and TBARS (39.78
      +/- 1.97 ppm). The samples with the best values in the antioxidant activity
      assays were evaluated in the anti-inflammatory tests. The DC root extract of P.
      velatum at a dose of 1 mg/ear produced the greatest reduction (84.96%) of the 2-O
      tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema. This extract also
      reduced the activity of the enzyme myeloperoxidase (MPO) (73.65%) at the same
      dose. In contrast, DC root extract of this species did not show significant
      inhibition of the increase in paw edema induced by carrageenan at the doses
      tested (100 mg/kg). CONCLUSION: These results support the traditional use of
      these plants as anti-inflammatory. DC extracts of P. velatum and MeOH extracts of
      P. bombycophole may be a potential resource of natural anti-inflammatory and
      antioxidant compounds, respectively. Additional studies must be done to identify
      the compounds responsible of the activity on these plants and to establish the
      mechanism of action.

PMID- 23127193
TI  - Growth kinetics of MPS-capped CdS quantum dots in self-assembled thin films.
AB  - For this study, we prepared colloidal CdS quantum dots using 3
      mercaptopropyltrimethoxysilane as capping agent. Colloidal CdS quantum dots were
      directly deposited on glass substrates by a spin-coating process. Coated
      substrates were heat-treated between 225 degrees C and 325 degrees C for various
      heat treatment time intervals to investigate the growth kinetics of the quantum
      dots. Results showed that sizes of the CdS quantum dots grew approximately from
      2.9 to 4.6 nm, and the E1s1s energy values shifted approximately from 3.3 to 2.7
      eV. Results showed that the average size of quantum dots increase by thermal
      treatment due to Ostwald ripening. The thermal process used to grow the size of
      quantum dots was examined according to the Lifshitz-Slyozov-Wagner theory. The
      activation energy of CdS quantum dots in thin films was calculated at
      approximately 44 kJ/mol.

PMID- 23127195
TI  - Nuclear and chloroplast DNA phylogeography of Ficus hirta: obligate pollination
      mutualism and constraints on range expansion in response to climate change.
AB  - This study uses a phylogeographic approach to investigate how interspecific
      interactions in an obligate pollination mutualism enhance or constrain dispersal
      and the range distributions of species through time. Fifteen populations of Ficus
      hirta, a bird-dispersed fig pollinated by a species-specific fig wasp, were
      sampled from Thailand to the northern limits of the tropical forest in China.
      These populations were assayed for six nuclear microsatellite loci and two
      intergenic chloroplast DNA sequences. Analyses of range expansion and genetic
      clustering indicated a relatively slow rate of range expansion from two or more
      southern glacial refugia. Low nuclear differentiation, combined with high
      interpopulation differentiation, and phylogeographic structuring of chloroplast
      variation indicated that seed dispersal has had a greater constraint than
      obligate interactions with fig wasps on the rate of post-glacial range expansion.
      This study is the first to investigate the phylogeographic history of a widely
      distributed southeast Asian tropical plant whose distribution extends to the
      northern limits of tropical forest habitat in China. It is also the first study
      of Ficus utilizing molecular data to evaluate whether species-specific
      pollination is a limitation or an aid to range expansion in response to climate
      change.

PMID- 23127196
TI  - Carnosine protects brain microvascular endothelial cells against rotenone-induced
      oxidative stress injury through histamine H1 and H2 receptors in vitro.
AB  - Although it is believed that carnosine has protective effects on various cell
      types, its effect on microvascular endothelial cells has not been well defined.
      In the present study, we investigated the protective effects of carnosine in
      microvascular endothelial cells using an in vitro rotenone-induced oxidative
      stress model. Mouse brain microvascular endothelial cells were exposed to 1
      MUmol/L rotenone for 18 h. In some experiments, carnosine (100 nmol/L-1 mmol/L)
      was added 30 min prior to rotenone exposure. When used, histamine receptor
      antagonists (100 nmol/L-10 MUmol/L) were added 15 min before carnosine treatment.
      After rotenone exposure, apoptosis of microvascular cells was analysed by Hoechst
      33342 staining, whereas mitochondrial membrane potential was assessed by JC-1
      staining. Intracellular carnosine and histamine levels were determined using HPLC
      or ultra-HPLC. Over the range 1 MUmol/L-1 mmol/L, carnosine concentration
      dependently decreased the number of apoptotic cells after 18 h exposure to
      rotenone. This effect was reversed by the histamine H1 receptor antagonists
      pyrilamine and diphenhydramine (1 and 10 MUmol/L) and the H2 receptor antagonists
      cimetidine (100 nmol/L-10 MUmol/L) and zolatidine (10 MUmol/L). alpha
      Fluoromethylhistidine (100 MUmol/L), a selective and irreversible inhibitor of
      histidine decarboxylase, also significantly inhibited the protective effects of
      carnosine. At 0.1 mmol/L, carnosine restored the decrease in mitochondrial
      membrane potential after 6 h exposure to 1 MUmol/L rotenone and this effect was
      also reversed by the H1 and H2 receptor antagonists. Moreover, intracellular
      carnosine levels increased as early as 1 h after carnosine treatment, whereas
      intracellular histamine levels increased 18 h after carnosine treatment. The
      results of the present study indicate that carnosine protects brain microvascular
      endothelial cells against rotenone-induced oxidative stress injury via histamine
      H1 and H2 receptors. The findings suggest that carnosine may be beneficial in the
      treatment of microvascular endothelial dysfunction induced by oxidative stress. 

PMID- 23127194
TI  - Mitogen- and stress-activated protein kinase 1 modulates photic entrainment of
      the suprachiasmatic circadian clock.
AB  - The master circadian clock in mammals, the suprachiasmatic nucleus (SCN), is
      under the entraining influence of the external light cycle. At a mechanistic
      level, intracellular signaling via the p42/44 mitogen-activated protein kinase
      pathway appears to play a central role in light-evoked clock entrainment;
      however, the precise downstream mechanisms by which this pathway influences clock
      timing are not known. Within this context, we have previously reported that light
      stimulates activation of the mitogen-activated protein kinase effector mitogen
      stress-activated kinase 1 (MSK1) in the SCN. In this study, we utilised MSK1(-/-)
      mice to further investigate the potential role of MSK1 in circadian clock timing
      and entrainment. Locomotor activity analysis revealed that MSK1 null mice
      entrained to a 12 h light/dark cycle and exhibited circadian free-running rhythms
      in constant darkness. Interestingly, the free-running period in MSK1 null mice
      was significantly longer than in wild-type control animals, and MSK1 null mice
      exhibited a significantly greater variance in activity onset. Further, MSK1 null
      mice exhibited a significant reduction in the phase-delaying response to an early
      night light pulse (100 lux, 15 min), and, using an 8 h phase-advancing 'jet-lag'
      experimental paradigm, MSK1 knockout animals exhibited a significantly delayed
      rate of re-entrainment. At the molecular level, early night light-evoked cAMP
      response element-binding protein (CREB) phosphorylation, histone phosphorylation
      and Period1 gene expression were markedly attenuated in MSK1(-/-) animals
      relative to wild-type mice. Together, these data provide key new insights into
      the molecular mechanisms by which MSK1 affects the SCN clock.

PMID- 23127197
TI  - Acculturation and self-rated health among Arctic indigenous peoples: a population
      based cross-sectional study.
AB  - BACKGROUND: Acculturation is for indigenous peoples related to the process of
      colonisation over centuries as well as the on-going social transition experienced
      in the Arctic today. Changing living conditions and lifestyle affect health in
      numerous ways in Arctic indigenous populations. Self-rated health (SRH) is a
      relevant variable in primary health care and in general public health assessments
      and monitoring. Exploring the relationship between acculturation and SRH in
      indigenous populations having experienced great societal and cultural change is
      thus of great importance. METHODS: The principal method in the Survey of Living
      Conditions in the Arctic (SLiCA) was standardised face-to-face interviews using a
      questionnaire. Very high overall participation rates of 83% were obtained in
      Greenland and Alaska, whilst a more conventional rate of 57% was achieved in
      Norway. Acculturation was conceptualised as certain traditional subsistence
      activities being of lesser importance for people's ethnic identity, and poorer
      spoken indigenous language ability (SILA). Acculturation was included in six
      separate gender- and country-specific ordinal logistic regressions to assess
      qualitative effects on SRH. RESULTS: Multivariable analyses showed that
      acculturation significantly predicted poorer SRH in Greenland. An increased
      subsistence score gave an OR of 2.32 (P<0.001) for reporting poorer SRH among
      Greenlandic men, while an increased score for Greenlandic women generated an OR
      of 1.71 (P=0.01). Poorer SILA generated an OR of 1.59 in men (p=0.03). In Alaska,
      no evidence of acculturation effects was detected among Inupiaq men. Among
      Inupiaq women, an increased subsistence score represented an increased odds of
      73% (p=0.026) for reporting poorer SRH. No significant effects of acculturation
      on SRH were detected in Norway. CONCLUSIONS: This study shows that aggregate
      acculturation is a strong risk factor for poorer SRH among the Kalaallit of
      Greenland and female Inupiat of Alaska, but our cross-sectional study design does
      not allow any conclusion with regard to causality. Limitations with regard to
      wording, categorisations, assumed cultural differences in the conceptualisation
      of SRH, and confounding effects of health care use, SES and discrimination, make
      it difficult to appropriately assess how strong this effect is though.

PMID- 23127198
TI  - Triage in opioid replacement therapy: what's the wait?
AB  - In Australia, a wait for Opioid Replacement Therapy (ORT) has been reported
      although the magnitude is unknown. This study examined data recorded by one urban
      publicly funded ORT clinic (from 2009 to 2011) to identify if people (n = 803)
      were waiting for ORT assessment appointments and to explore how triage influences
      access to ORT. Data analysis incorporated descriptive methods and the use of
      Kaplan-Meier estimator of the cumulative incidence function. The implications and
      limitations of this study are included with further research suggestions.

PMID- 23127199
TI  - Alcohol and club drug use among same-sex attracted young people: associations
      with frequenting the lesbian and gay scene and other bars and nightclubs.
AB  - This study aimed to determine whether the lesbian and gay "scene" of bars and
      nightclubs is a more common site for club drug use than other bars and clubs. A
      cross-sectional, online survey was conducted with 254 same-sex attracted women
      and 318 men aged 18-25 in Sydney, Australia. Drug use was more likely in those
      who attended any venue type more frequently. Men, but not women, were more likely
      to report drug use in lesbian and gay venues than other venues. Club drug use may
      be more normalized within the lesbian and gay scene than elsewhere, particularly
      among young men. The study's limitations are noted.

PMID- 23127200
TI  - Assessing covariates of drug use trajectories among adolescents admitted to a
      drug addiction center: mental health problems, therapeutic alliance, and
      treatment persistence.
AB  - This study aimed to assess covariates of drug use trajectories among 102
      adolescents admitted to a drug user treatment program between November 2005 and
      November 2006 in Quebec, Canada. The influences of mental health, therapeutic
      alliance, and treatment persistence were examined. The Addiction Severity Index
      was used to measure drug use severity and mental health problems; the California
      Psychotherapy Alliance Scales was used for therapeutic alliance. latent growth
      curve analysis showed associations between (1) mental health and initial drug use
      severity; (2) therapeutic alliance and initial drug use severity; and (3) number
      of post-treatment sessions attended and drug use severity over time.

PMID- 23127201
TI  - Monitoring and switching patterns of patients with chronic myeloid leukemia
      treated with imatinib in community settings: a chart review analysis.
AB  - OBJECTIVES: Monitoring treatment response is an integral part of chronic myeloid
      leukemia (CML) treatment. The guidelines recommend regular monitoring using
      standard methods (e.g., real-time quantitative polymerase chain reaction based on
      the international scale for molecular response) and treatment adjustment when
      failure is detected among patients treated with imatinib. The objective of this
      study was to assess the real-world monitoring and therapy adjustment in this
      patient population in the US. METHODS: Twenty-nine physicians from community
      practices across the US participated in an online chart review. Adult patients
      with chronic phase CML who initiated imatinib as first-line therapy during 2006
      2010 were selected. Information was collected up to 36 months after imatinib
      initiation, including response monitoring, response status, and therapy
      adjustment upon treatment failure. RESULTS: The study included 297 eligible
      patients. By 18 months, 47% of patients had received cytogenetic response
      assessment continuously as recommended by the guidelines. The corresponding
      proportion was 39% for continuous molecular response assessment. Among patients
      who experienced treatment failure by 18 months, only 14%-38% of patients switched
      to a second-generation tyrosine kinase inhibitor as recommended by the National
      Comprehensive Cancer Network and the European Leukemia Net guidelines.
      LIMITATIONS: Major limitations included limited generalizability and the
      inability to accurately assess molecular response due to the variations in
      testing methods during the study period. CONCLUSIONS: Based on the guidelines,
      the rates of treatment monitoring and switching upon failure were low,
      demonstrating the need for improvement in CML care in community settings in the
      US.

PMID- 23127202
TI  - Aerial pollutants in swine buildings: a review of their characterization and
      methods to reduce them.
AB  - The swine industry follows a large increase of meat production since the 1950s
      causing the development of bigger swine buildings which involves a raise of
      pollutants emissions. Due to recent anthropological pressures concerning the
      animal welfare, the limitation of neighborhood disturbances and atmospheric
      pollutions limitations, the livestock farming has to adapt their management
      methods to reduce or treat the aerial pollutants emissions. Through the diversity
      of livestock barns configurations, their climatic location, their size, and their
      management, we thus propose hereafter a critical review of the characterizations
      of these aerial pollutants. This is realized by distinguishing both solids and
      gaseous emissions and by referencing the measurements methods mainly used to
      analyze and quantify airborne particles, odorants, and gaseous compounds in the
      atmosphere of swine buildings. The origins of these pollutants are focused and
      the sturdiest techniques for concentration measurements are highlighted. Finally,
      we discuss pollutants abatement techniques criticizing their implementation in
      swine buildings and emphasizing the use of biological ways such as biofiltration
      for gases and odors treatment.

PMID- 23127203
TI  - Chronic obstructive pulmonary disease phenotype desaturator with hypoxic vascular
      remodelling and pulmonary hypertension obtained by cluster analysis.
AB  - Significant heterogeneity of clinical presentation and disease progression
      exists within chronic obstructive pulmonary disease (COPD). This article
      discusses and refines the concept of desaturator phenotypes in COPD with
      pulmonary hypertension (PH) obtained by cluster analysis and presents a pattern
      of phenotypic markers that could be used as a framework for future diagnosis and
      research. Nocturnal oxygen desaturation results in sleep disturbances which
      predispose to nocturnal cardiac dysrhythmias, PH and possibly nocturnal death,
      particularly during acute exacerbations. We assume that in patients with COPD at
      least two factors play a role in PH: the severity of pulmonary impairment, and
      the severity of systemic nocturnal hypoxaemia due to reduced pulmonary functions.
      Establishing a common language for future research will facilitate our
      understanding and management of such a disease. This knowledge could lead to
      different pharmacological treatments and other interventions directed at specific
      phenotypic groups.

PMID- 23127204
TI  - Pharmacokinetics and safety profile of a novel progesterone aqueous formulation
      administered by the s.c. route.
AB  - A novel aqueous progesterone formulation was developed. Study I: Three-way cross
      over, open-label study in 24 post-menopausal women. Comparison of the
      pharmacokinetic profiles of a single 100 mg dose of test product administered by
      subcutaneous (s.c.) and intramuscular (i.m.) injection and an i.m. reference oily
      product. Study II: Three-way cross-over open-label study of 25, 50 and 100 mg
      s.c. single doses of the aqueous formulation in 12 post-menopausal women. Study
      III: Parallel-group, observer-blinded study in 25 fertile women administered
      multiple s.c. 25 and 50 mg doses of the aqueous formulation once daily for 11
      days. Baseline-corrected pharmacokinetic parameters were evaluated. Aqueous
      formulation (100 mg) was promptly absorbed, achieving progesterone peak serum
      levels at an earlier time than the reference (1 h vs. 7 h; p < 0.0001). Test and
      reference were bioequivalent in the extent of exposure: confidence intervals for
      AUC(0-t) geometric means ratios were within the pre-specified 80-125% limits.
      Pharmacokinetics was linear over the range of doses studied. Steady state was
      reached within 4 days of multiple dose treatment. All treatments were well
      tolerated. Considering the advantages given by the possibility of self
      medication, the s.c. aqueous formulation could offer a convenient alternative for
      patients on assisted reproductive technology treatments.

PMID- 23127205
TI  - Dapagliflozin: a review on efficacy, clinical effectiveness and safety.
AB  - INTRODUCTION: The prevalence of type 2 diabetes mellitus has reached epidemic
      proportions. Progressive deterioration in glycaemic control and the current
      limitations of existing therapies such as weight gain and hypoglycaemia led us to
      welcome the first of a new class of drugs. Sodium-glucose co-transporter 2
      (SGLT2) inhibitors represent a novel mode of therapy independent of insulin
      secretion or action. By blocking glucose reabsorption in the kidney they lead to
      an increase in urinary glucose excretion with reduction in plasma glucose levels.
      AREAS COVERED: In this article, we will review inhibition of SGLT2 as a novel
      strategy for the treatment of type 2 diabetes mellitus with dapagliflozin .
      PubMed and MEDLINE were searched for literature published up to July 2012, for
      efficacy, clinical effectiveness and safety reports of dapagliflozin. EXPERT
      OPINION: Improvement in glycaemic control with a low risk of hypoglycaemia,
      concomitant weight loss and the potential of lowering of blood pressure make
      SGLT2 inhibition an attractive approach using dapagliflozin therapy. Many SGLT2
      inhibitors are undergoing Phase III clinical trials and more are in Phase I and
      II clinical trials.

PMID- 23127206
TI  - Effects of acute sacral neuromodulation on bladder reflex in complete spinal cord
      injury rats.
AB  - BACKGROUND: Neurogenic bladder associated with spinal cord injury (SCI) often
      results in serious disruption of lower urinary tract function. Compared to
      conventional therapies, sacral neuromodulation (SNM) may offer an alternative,
      non-destructive treatment for SCI patients with bladder dysfunction.
      Understanding bladder reflex changes following SCI and the effects of SNM may
      yield new insights for innovative use of this promising technique. Using a SCI
      rat model developed in this study, we investigated: 1) the bladder responses with
      different grades of bladder filling in intact and SCI rats; and 2) the effects of
      acute SNM on bladder reflex responses in SCI rats. METHODS: An SCI rat model with
      overactive bladder was developed and evaluated in this study to examine the
      effects of acute SNM on bladder reflex in complete SCI rats. Twelve adult female
      Sprague-Dawley rats were divided into three groups; group I: spinally intact rats
      (N = 4), group II: transected (T9-T10) rats (N = 4), i.e., SCI rats, and group
      III: SCI rats with SNM treatment (N = 4). All rats were anesthetized and set up
      for continuous saline infusion. Cystometric parameters, including contraction
      period, contraction duration, bladder peak pressure, and number of uninhibited
      contractions, were analyzed and compared between groups and between conditions
      with and without SNM treatment for SCI rats. RESULTS: In the intact rats, the
      frequency of bladder contraction was dependent upon the rate of bladder filling,
      while the spinal transected rats exhibited large fluctuation and demonstrated
      different patterns in response to saline infusion. Moreover, the bladder in SCI
      rats demonstrated an increased contraction period and a decreased contraction
      strength compared to the intact rats (all p < 0.05). In SCI rats under acute SNM
      treatment, bladder contraction period and duration tended to become longer, and
      the bladder peak pressure was decreased. The accumulating evidence indicated that
      acute SNM had inhibiting effects for bladder overactivity following SCI.
      CONCLUSION: The spinal rat model developed in this study was suitable to
      investigate the effect of sacral neural stimulation on micturition reflex. The
      results of present study demonstrated that the micturition reflex can be
      modulated by sacral neural stimulation.

PMID- 23127208
TI  - Outcrossing rates in two self-compatible, hybridising Rhinanthus species:
      implications for hybrid formation.
AB  - The congeners Rhinanthus angustifolius and Rhinanthus minor, two annual
      hemiparasites pollinated by bumblebees, are known to hybridise in the wild. Both
      species are self-compatible, but the capacity for autonomous selfing is higher in
      R. minor. This suggests a difference in realized outcrossing rates, which have
      not been determined before in these species. Using microsatellites, both species
      turned out to have mixed mating systems, but with a much lower multilocus
      outcrossing rate (0.13) for R. minor compared to R. angustifolius (0.76). We
      hypothesised that a higher outcrossing rate should lead to a higher chance of
      heterospecific pollination, and we therefore determined the rate of hybrid
      formation on each species in an artificial mixed population. Hybrid seeds were
      produced at low frequency (4.5%), and no significant difference was found between
      the species. It is therefore likely that post-pollination processes influence
      hybrid seed formation to counteract the expected difference in heterospecific
      pollen deposition. We checked fruit set, seed set and the rate of autonomous
      selfing in controlled crosses in the greenhouse in 2 years, and found that fruit
      set (2003) or seed set (2010) were lower in R. angustifolius * R. minor crosses
      relative to the reciprocal cross. Hybrid seeds produced on R. angustifolius also
      had a much lower germination rate, so most of the established F1 hybrid plants
      have the R. minor cytoplasm. The formation of advanced hybrids depends on
      pollinator preference, which is biased towards R. angustifolius if present in
      sufficient numbers, because it offers more rewards.

PMID- 23127207
TI  - Physical mapping resources for large plant genomes: radiation hybrids for wheat D
      genome progenitor Aegilops tauschii.
AB  - BACKGROUND: Development of a high quality reference sequence is a daunting task
      in crops like wheat with large (~17Gb), highly repetitive (>80%) and polyploid
      genome. To achieve complete sequence assembly of such genomes, development of a
      high quality physical map is a necessary first step. However, due to the lack of
      recombination in certain regions of the chromosomes, genetic mapping, which uses
      recombination frequency to map marker loci, alone is not sufficient to develop
      high quality marker scaffolds for a sequence ready physical map. Radiation hybrid
      (RH) mapping, which uses radiation induced chromosomal breaks, has proven to be a
      successful approach for developing marker scaffolds for sequence assembly in
      animal systems. Here, the development and characterization of a RH panel for the
      mapping of D-genome of wheat progenitor Aegilops tauschii is reported. RESULTS:
      Radiation dosages of 350 and 450 Gy were optimized for seed irradiation of a
      synthetic hexaploid (AABBDD) wheat with the D-genome of Ae. tauschii accession
      AL8/78. The surviving plants after irradiation were crossed to durum wheat
      (AABB), to produce pentaploid RH1s (AABBD), which allows the simultaneous mapping
      of the whole D-genome. A panel of 1,510 RH1 plants was obtained, of which 592
      plants were generated from the mature RH1 seeds, and 918 plants were rescued
      through embryo culture due to poor germination (<3%) of mature RH1 seeds. This
      panel showed a homogenous marker loss (2.1%) after screening with SSR markers
      uniformly covering all the D-genome chromosomes. Different marker systems mostly
      detected different lines with deletions. Using markers covering known distances,
      the mapping resolution of this RH panel was estimated to be <140kb. Analysis of
      only 16 RH lines carrying deletions on chromosome 2D resulted in a physical map
      with cM/cR ratio of 1:5.2 and 15 distinct bins. Additionally, with this small set
      of lines, almost all the tested ESTs could be mapped. A set of 399 most
      informative RH lines with an average deletion frequency of ~10% were identified
      for developing high density marker scaffolds of the D-genome. CONCLUSIONS: The RH
      panel reported here is the first developed for any wild ancestor of a major
      cultivated plant species. The results provided insight into various aspects of RH
      mapping in plants, including the genetically effective cell number for wheat (for
      the first time) and the potential implementation of this technique in other plant
      species. This RH panel will be an invaluable resource for mapping gene based
      markers, developing a complete marker scaffold for the whole genome sequence
      assembly, fine mapping of markers and functional characterization of genes and
      gene networks present on the D-genome.

PMID- 23127209
TI  - Associations between aberrant DNA methylation and transcript levels of DNMT1 and
      MBD2 in CD4+T cells from patients with systemic lupus erythematosus.
AB  - BACKGROUND/OBJECTIVES: It seems that global DNA hypomethylation in CD4+T cells is
      linked to the pathogenesis of systemic lupus erythematosus (SLE). However, the
      underlying mechanism by which SLE patients show hypomethylated DNA remains
      unclear. This study explored the relationship between DNA methylation patterns
      and expression levels of DNA methyltransferases (DNMT1) and MBD2 in CD4+T cells
      of SLE patients. METHODS: CD4+T cells were obtained from 30 patients with SLE and
      18 normal controls. The global DNA methylation levels in CD4+T cells were
      evaluated by the Methyflash DNA methylation quantification kit. The mRNA levels
      of DNMT1 and MBD2 were quantified by quantitative real-time polymerase chain
      reaction. RESULTS: SLE patients had significantly lower global DNA methylation
      levels than controls, and the global DNA methylation was inversely correlated
      with the SLE disease activity index (SLEDAI). The mRNA levels of DNMT1 in SLE
      patients were significantly lower than that of controls and there was no
      correlation between DNMT1 mRNA levels and SLEDAI but there was a positive
      correlation between DNMT1 mRNA levels and global DNA methylation. The mRNA levels
      of MBD2 in SLE patients were significantly higher than in controls, and there was
      positive correlation between MBD2 mRNA levels and SLEDAI and an inverse
      correlation between MBD2 mRNA levels and global DNA methylation. CONCLUSIONS:
      Global DNA hypomethylation may play a pivotal role in the pathogenesis of SLE.
      Abnormal expression levels of DNMT1 and MBD2 mRNA may be important causes of the
      global hypomethylation observed in CD4+T cells in SLE.

PMID- 23127210
TI  - Citrullination of fibronectin modulates synovial fibroblast behavior.
AB  - INTRODUCTION: Rheumatoid arthritis is an autoimmune arthritis characterized by
      joint destruction. Anti-citrullinated protein antibodies are pathologic in
      rheumatoid arthritis, but the role of the citrullinated proteins themselves is
      much less clear. Citrullination is the conversion of the arginine residues of a
      protein to citrulline. In the inflamed rheumatoid joint there is increased
      protein citrullination. Several proteins are citrullinated in rheumatoid
      arthritis, including collagen type II, fibrinogen, and fibronectin. Fibronectin
      is thought to mediate the adhesion of joint-invading synovial fibroblasts to the
      rheumatoid cartilage in addition to regulating other synovial fibroblast
      functions. However, the effect of citrullinated fibronectin on synovial
      fibroblasts is unknown. METHODS: To investigate the effect of citrullinated
      fibronectin on synovial fibroblast behavior, we cultured normal murine, arthritic
      murine, and human rheumatoid synovial fibroblasts. We then compared several
      synovial fibroblast functions in the presence of fibronectin versus citrullinated
      fibronectin. We assessed adhesion with time-lapse microscopy, migration with
      transwell assays, focal adhesion kinase and paxillin phosphorylation by western
      blot, and focal matrix degradation by fluorescent gelatin degradation. RESULTS:
      Normal synovial fibroblasts have impaired adhesion, spreading, migration, and
      integrin-mediated phosphorylation of focal adhesion kinase and paxillin on
      citrullinated fibronectin. Murine arthritic and human rheumatoid synovial
      fibroblasts also have impaired adhesion and spreading on citrullinated
      fibronectin, but focal matrix degradation is unaffected by citrullinated
      fibronectin. CONCLUSION: Citrullination of fibronectin alters synovial fibroblast
      behavior and may affect how these cells adhere to and invade the joint and travel
      through the bloodstream. This work suggests an important role for the interaction
      of synovial fibroblasts with citrullinated matrix in the pathophysiology of
      rheumatoid arthritis.

PMID- 23127211
TI  - Smoking behaviour in pregnancy and its impact on smoking cessation at various
      intervals during follow-up over 21 years: a prospective cohort study.
AB  - OBJECTIVE: To determine whether mothers who quit or reduce their level of smoking
      in pregnancy comprise a group of health-conscious women who are disproportionally
      likely to adopt a healthier smoking lifestyle in the medium to longer term,
      compared with women who continue to smoke during pregnancy. DESIGN: A prospective
      cohort study. SETTING: A public hospital in Australia. POPULATION: A cohort of
      6703 individual mothers who completed both initial phases of data collection in
      1981-1983; mothers who smoked daily (2992) before pregnancy were included in this
      study. METHODS: Mothers were interviewed at 3-5 days post-delivery, 6 months, 5
      years, 14 years and 21 years to determine their smoking status. An inverse
      probability-weighted Poisson regression with a robust error variance was fitted
      to the data using a log-link function and a binary response variable for smoking
      outcome, and adjusting for several possible confounding factors. MAIN OUTCOME
      MEASURE: Smoking cessation at several follow-up points, for up to 21 years.
      RESULTS: Of the mothers who smoked daily before pregnancy, 12, 23, 37 and 41%
      reported having ceased smoking at 6 months and at 5, 14 and 21 years,
      respectively. The decision to quit smoking during pregnancy was found to be
      independently associated with a higher rate ratio (RR) of smoking cessation at 6
      months (RR 30.60, 95% CI 20.50-45.69), 5 years (RR 4.36; 95% CI 3.61-5.27), 14
      years (RR 2.42, 95% CI 2.12-2.75) and 21 years (RR 1.86; 95% CI 1.60-2.15), after
      adjusting for several possible confounding factors. CONCLUSIONS: Pregnancy
      appears to be an opportunity for successfully quitting smoking, regardless of
      socio-economic circumstances or demographic background.

PMID- 23127212
TI  - Hydrogen-bond and solvent dynamics in transition metal complexes: a combined
      simulation and NMR-investigation.
AB  - Self-assembling ligands through complementary hydrogen-bonding in the
      coordination sphere of a transition metal provides catalysts with unique
      properties for carbon-carbon and carbon-heteroatom formation. Their most
      distinguishing chemical bonding pattern is a double-hydrogen-bonded motif, which
      determines much of the chemical functionality. Here, we discuss the possibility
      of double proton transfer (DPT) along this motif using computational and
      experimental methods. The infrared and NMR spectral signatures for the double
      hydrogen-bonded motif are analyzed. Atomistic simulations and experiments suggest
      that the dynamics of the catalyst is surprisingly complex and displays at least
      three different dynamical regimes which can be distinguished with NMR
      spectroscopy and analyzed from computation. The two hydrogen bonds are kept
      intact and in rapid tautomeric exchange down to 125 K, which provides an estimate
      of 5 kcal/mol for the barrier for DPT. This is confirmed by the simulations which
      predict 5.8 kcal/mol for double proton transfer. A mechanistic interpretation is
      provided and the distribution of the solvent shell surrounding the catalyst is
      characterized from extensive simulations.

PMID- 23127213
TI  - On the relationship between coefficient alpha and composite reliability.
AB  - Cronbach's coefficient alpha is the most widely used estimator of the reliability
      of tests and scales. However, it has been criticized as being a lower bound and
      hence underestimating true reliability. A popular alternative to coefficient
      alpha is composite reliability, which is usually calculated in conjunction with
      structural equation modeling. A quantitative analysis of 2,524 pairs of
      coefficient alpha and composite reliability values derived from empirical
      investigations revealed that although the average composite reliability value
      (.86) exceeded the average corresponding coefficient alpha value (.84), the
      difference was relatively inconsequential for practical applications such as meta
      analysis.

PMID- 23127214
TI  - Postcranial sex estimation of individuals considered Hispanic.
AB  - When forensic anthropologists estimate the sex of Hispanic skeletal remains using
      nonpopulation specific metric methods, initial observations cause males to
      frequently misclassify as female. To help improve these methods, this research
      uses postcranial measurements from United States-Mexico border migrant fatalities
      at the Pima County Office of the Medical Examiner in Tucson, Arizona, as well as
      Hispanic individuals from the Forensic Anthropology Data Bank. Using a total of
      114 males and 28 females, sectioning points and discriminant functions provide
      classification rates as high as 89.43% for Hispanic individuals. A test sample
      assessed the reliability of these techniques resulting in accuracy up to 99.65%.
      The clavicle maximum length measurement provides the best univariate estimate of
      sex, while the radius provides the best multivariate estimated of sex. The
      results of this research highlight the need for population specific data in the
      creation of a biological profile, especially when working with individuals
      considered Hispanic.

PMID- 23127215
TI  - Associations of soluble fiber, whole fruits/vegetables, and juice with plasma
      Beta-carotene concentrations in a free-living population of breast cancer
      survivors.
AB  - OBJECTIVE: Soluble fiber and the physical state of fruits/vegetables affect
      plasma beta-carotene concentrations; however, most of this research was conducted
      in laboratory-based settings. These analyses investigated the relationship
      between soluble fiber and juiced versus whole fruits/vegetables to plasma beta
      carotene concentrations in a free-living population. METHOD: This cross-sectional
      analysis used 12-month follow-up data from the Women's Healthy Eating & Living
      Study (1995-2006), a study to improve diet in breast cancer survivors in the
      Western United States. The dietary nutrients considered in this analysis included
      intake of soluble fiber (g), beta-carotene from fruit/vegetable juice (mg), and
      beta-carotene from whole fruits/vegetables (mg). A linear regression model was
      used to assess the relationship of the variables to plasma beta-carotene
      concentrations. RESULTS: Out of 3,088 women enrolled in the Women's Healthy
      Eating & Living Study, 2,397 women had complete data (mean age = 54). The final
      model accounted for approximately 49% of the explained variance in plasma beta
      carotene concentrations. Fruit/vegetable juice had the largest positive relation
      to plasma beta-carotene concentrations (standardized parameter estimate = 0.23, p
      < 0.01), followed by whole fruits/vegetables (standardized parameter estimate =
      0.09, p < 0.01). CONCLUSION: Soluble fiber may inhibit beta-carotene absorption;
      therefore, consumption of juice may increase plasma beta-carotene concentrations
      more than whole fruits/vegetables in free-living populations.

PMID- 23127216
TI  - Epidemiology of infertility: a population-based study in Babol, Iran.
AB  - The aim of researchers in the present study was to determine the prevalence of
      infertility and self-reported cause of infertility in Babol, Iran and then
      identify the factors associated with infertility. A retrospective epidemiologic
      study was conducted of characteristics of urban and rural women related to
      infertility. A total of 1,140 women aged 20-45 years were selected using cluster
      sampling. Of these 1,140 women, 59 (5.2%) (CI 4.2, 6.2) were voluntarily
      childless. Of the remaining 1,081 women, 913 (84.5%) (CI 82.5, 86.5) reported no
      difficulties in having children, and the remaining 168 (15.5%) (CI 13.5, 17.5)
      experienced difficulty conceiving at some stage in their lives. The prevalence of
      ever having primary infertility was 4.3% (CI 2.3, 6.3). The most frequently self
      reported causes of infertility in this study were ovulation problems (39.2%).
      Infertile women were significantly more likely to have a higher age at marriage
      (p = 0.001), lower education (p = 0.006), higher body mass index (p = 0.0001),
      long-term health problems (p = 0.0001), a partner who smoked (p = 0.029), and
      past history of tubal or ectopic pregnancy (p = 0.002). These risk factors may
      help inform reproductive health clinics and primary healthcare centers about
      factors associated with infertility.

PMID- 23127217
TI  - The association between employment status and metabolic syndrome in women:
      modifying effect of education.
AB  - The aim of the researchers in this study was to examine the relations of paid
      work versus housework and educational level to metabolic syndrome in women. The
      study sample consisted of women who participated in a baseline survey of the
      Heart of Balcova Project, which is an ongoing cohort study in Izmir, Turkey. A
      randomly selected subsample of women who were aged 30-64 years and who were not
      retired or unemployed was derived from the individuals who participated in the
      Heart of Balcova Project. All data were collected through face-to-face interviews
      with 191 workers and 342 housewives. The association between employment status
      and metabolic syndrome was explored using multiple logistic regression models.
      The prevalence of metabolic syndrome was significantly higher among housewives
      than among workers. Among the women with a high educational level, odds of
      metabolic syndrome were significantly higher for housewives than for those who
      were employed. An association between employment status and metabolic syndrome
      was not observed in the group with a low level of education. The findings
      revealed that educational level had a modifying effect on the relationship
      between employment status and metabolic syndrome among women and thus has
      implications for improving the understanding of the importance of health and
      educational opportunities for housewives.

PMID- 23127218
TI  - Women's perceived benefits of exercise during and after breast cancer treatment.
AB  - Empirical data support the benefits of physical activity for women who have been
      diagnosed with breast cancer. However, the experience of exercising during or
      after breast cancer treatment has not been fully documented. The purpose of the
      researchers in this study was to provide an in-depth description of women's
      experiences with exercising during or after their breast cancer treatments,
      specifically, their perceptions of the benefits they experienced as a result of
      participation in an individualized exercise program that included cardiovascular
      and resistance activities. Forty-five women who had been diagnosed with breast
      cancer within the previous two years were recruited from two oncology practices
      after electing to enroll in an exercise program. Data were collected between
      September 2006 and August 2007 through in-depth interviews at various stages in
      the exercise program and analyzed simultaneously using thematic analysis methods.
      Whether in treatment or post-treatment, women attributed psychological, physical,
      and social benefits to their participation in the exercise program. Participants
      credited the program with helping them to feel better, regain control over their
      bodies and their lives, manage their emotions, and prepare them to live
      healthfully going forward. These results provide insight into the specific ways
      women experience exercise during and after their breast cancer treatments.

PMID- 23127219
TI  - Mechanistic and "natural" body metaphors and their effects on attitudes to
      hormonal contraception.
AB  - A small, self-selected convenience sample of male and female contraceptive users
      in the United Kingdom (n = 34) were interviewed between 2006 and 2008 concerning
      their feelings about the body and their contraceptive attitudes and experiences.
      The interviewees were a sub-sample of respondents (n = 188) who completed a paper
      based questionnaire on similar topics, who were recruited through a poster placed
      in a family planning clinic, web-based advertisements on workplace and university
      websites, and through direct approaches to social groups. The bodily metaphors
      used when discussing contraception were analyzed using an interpretative
      phenomenological analytical approach facilitated by Atlas.ti software. The
      dominant bodily metaphor was mechanistic (i.e.,"body as machine"). A subordinate
      but influential bodily metaphor was the "natural" body, which had connotations of
      connection to nature and a quasi-sacred bodily order. Interviewees drew upon this
      "natural" metaphorical image in the context of discussing their anxieties about
      hormonal contraception. Drawing upon a "natural," non-mechanistic body image in
      the context of contraceptive decision-making contributed to reluctance to use a
      hormonal form of contraception. This research suggests that clinicians could
      improve communication and advice about contraception by recognizing that some
      users may draw upon non-mechanistic body imagery.

PMID- 23127220
TI  - Midlife crisis perceptions, experiences, help-seeking, and needs among multi
      ethnic malaysian women.
AB  - In the present study, researchers explored attitudes toward midlife crises,
      experience with midlife crises, help-seeking, and needs among multi-ethnic
      Malaysian women. A total of 14 focus group discussions were conducted with 89
      Malaysian women of different ages and socioeconomic backgrounds. Women expressed
      concern over physical aging and decline in their physical functional health.
      Having a midlife crisis was frequently reported. Issues that were frequently
      reported to trigger a midlife crisis, such as empty nest syndrome, impact of
      aging on sexual and reproductive function, extended parenthood, caring for aging
      or ill parents, and career challenges were noted by the study participants
      (listed here in order of most to least frequently reporting of these themes
      across the group discussions). Overall, these issues were associated with
      attitudes about aging. A comparatively less open attitude toward sexual attitudes
      and help-seeking for sexual problems were found among the Malay and Indian women.
      This may imply that intervention to increase positive attitudes concerning both
      sexuality and help-seeking intentions should be culturally specific. The use of
      religious coping for comfort and consolation was frequently reported; therefore,
      those providing midlife crisis prevention and intervention programs should
      consider involving faith-based interventions in the Malaysian setting.

PMID- 23127222
TI  - Cytotoxic and antioxidant properties of selected Scutellaria species from the
      Western Ghats of Peninsular India.
AB  - CONTEXT: Scutellaria (Lamiaceae), commonly known as 'Skullcaps', has been
      extensively used in Traditional Chinese Medicine (TCM). Recently, much emphasis
      has been given to this genus due to the rich source of bioflavonoids that
      contribute to its biological properties. Therefore, different species of
      Scutellaria are being explored worldwide. OBJECTIVES: Cytotoxic, antioxidant, and
      phytochemical properties of Scutellaria colebrookiana Benth and S. violacea
      (Heyne ex Benth) Don collected (October 2009-February 2010) from Western Ghats of
      India have been analysed. MATERIALS AND METHODS: In vitro cytotoxicity and free
      radical scavenging effects of root extracts in various solvents were analysed.
      Spectrophotometric and HPLC methods were performed for phytochemical analysis.
      RESULTS: Chloroform extract exhibited significant cytotoxicity in Dalton's
      Lymphoma Ascites (DLA) and Ehrlich Ascites Carcinoma (EAC) cells with IC(50)
      values 150 and 140 ug/mL for S. colebrookiana and 250 and 280 ug/mL for S.
      violacea, respectively. Moreover, the extract was effective in scavenging free
      radicals and inhibiting membrane peroxidation in vitro with IC(50) values 158.3
      and 167.5 (superoxide), 17.5 and 28.0 (hydroxyl), 76.25 and 69.75 (DPPH), 24.5
      and 28.0 (ABTS), 69.75 and 64.6 (lipid peroxidation), 41 and 31.5 ug/mL
      (erythrocyte hemolysis), respectively. Antioxidant effect observed with acetone
      extract was also comparable to that of chloroform extract. Phytochemical
      screening revealed the presence of baicalein. DISCUSSION AND CONCLUSION:
      Scutellaria species of Western Ghats showed cytotoxic and antioxidant potential
      and the presence of baicalein. This suggests that S. colebrookiana and S.
      violacea could be used as alternative sources for baicalein in view of the
      reported scarcity of S. baicalensis.

PMID- 23127223
TI  - Studying alcohol in its societal context: The Finnish tradition of analysis of
      population surveys.

PMID- 23127224
TI  - Characteristics of phase-change materials containing oxide nano-additives for
      thermal storage.
AB  - In this study, the authors report the production of nanocomposite-enhanced phase
      change materials (NEPCMs) using the direct-synthesis method by mixing paraffin
      with alumina (Al2O3), titania (TiO2), silica (SiO2), and zinc oxide (ZnO) as the
      experimental samples. Al2O3, TiO2, SiO2, and ZnO were dispersed into three
      concentrations of 1.0, 2.0, and 3.0 wt.%. Through heat conduction and
      differential scanning calorimeter experiments to evaluate the effects of varying
      concentrations of the nano-additives on the heat conduction performance and
      thermal storage characteristics of NEPCMs, their feasibility for use in thermal
      storage was determined. The experimental results demonstrate that TiO2 is more
      effective than the other additives in enhancing both the heat conduction and
      thermal storage performance of paraffin for most of the experimental parameters.
      Furthermore, TiO2 reduces the melting onset temperature and increases the
      solidification onset temperature of paraffin. This allows the phase-change heat
      to be applicable to a wider temperature range, and the highest decreased ratio of
      phase-change heat is only 0.46%, compared to that of paraffin. Therefore, this
      study demonstrates that TiO2, added to paraffin to form NEPCMs, has significant
      potential for enhancing the thermal storage characteristics of paraffin.

PMID- 23127226
TI  - Implantable cardioverter-defibrillator shock during physical activity:
      appropriate or inappropriate shock?

PMID- 23127227
TI  - Thiazolidinediones improve hepatic fibrosis in rats with non-alcoholic
      steatohepatitis by activating the adenosine monophosphate-activated protein
      kinase signalling pathway.
AB  - Thiazolidinediones (TZDs) markedly reduce hepatic steatosis in both rodents and
      humans. However, the effects and mechanisms of action of TZDs on hepatic fibrosis
      remain unclear. The aim of the present study was to determine the effects of TZDs
      on histological changes in the liver and on the modulation by adiponectin via the
      AMP-activated protein kinase (AMPK) signalling pathway in rats with non-alcoholic
      steatohepatitis (NASH). Forty rats were divided into normal control, high-fat
      diet (HFD), pioglitazone control and pioglitazone intervention groups. After 24
      weeks treatment with pioglitazone (10 mg/kg per day by gavage), changes in liver
      histology, serum aminotransaminase, triglyceride (TG), free fatty acid (FFA),
      glucose, insulin, adiponectin and transforming growth factor (TGF)-beta1
      concentrations and hepatic adiponectin, AMPK, alpha-smooth muscle actin (alpha
      SMA) and collagen I expression were evaluated. The degree of hepatic steatosis
      and fibrosis was significantly higher in HFD-induced NASH rats compared with
      normal controls, as were serum concentrations of aminotransaminase, TG, FFA,
      glucose, insulin and TGF-beta1 and hepatic expression of alpha-SMA and collagen I
      protein. Serum adiponectin concentrations and hepatic expression of adiponectin
      mRNA and AMPK protein were significantly lower in the HFD-induced NASH rats
      compared with the normal control. Pioglitazone significantly reduced the degree
      of hepatic steatosis and fibrosis, as well as serum concentrations of
      aminotransaminase, TG, FFA, glucose, insulin and TGF-beta1 and hepatic expression
      of alpha-SMA and collagen I protein. In addition, pioglitazone significantly
      increased serum adiponectin concentrations and hepatic expression of adiponectin
      mRNA and AMPK protein. In conclusion, the TZD pioglitazone improved hepatic
      fibrosis in rats with NASH by upregulating adiponectin expression and activating
      AMPK, thus subsequently inhibiting the activation of hepatic stellate cells and
      the overproduction of extracellular matrix. 

PMID- 23127229
TI  - The benefits of being green.

PMID- 23127230
TI  - Hooking up in the college context: the event-level effects of alcohol use and
      partner familiarity on hookup behaviors and contentment.
AB  - The current study examined hooking up experiences through event-level analyses,
      including the connections involving alcohol use, the extent of physical contact,
      and postevaluations of the hookup event. Participants were 828 college students
      (67.0% female). Of students who reported hooking up sometime within the past year
      (54.8%), chi-square analyses revealed that they were more likely to have been
      drinking when they met their partners the night of the hookup. Females who were
      drinking beforehand and females who met their partners that night were more
      likely to feel discontent with their hookup decisions. Among participants who
      consumed alcohol prior to their last hookup, a notable 30.7% of females and 27.9%
      of males indicated that they would likely not have hooked up with their partners
      had alcohol not been involved. Further, 34.4% of females and 27.9% of males
      indicated that they would not have gone as far physically if they had not been
      drinking. Among participants who reported both drinking beforehand and hooking up
      with unfamiliar partners, greater number of drinks consumed was associated with
      more advanced sexual behaviors. The current findings highlight the potential
      risks associated with alcohol use in the hooking up culture. 

PMID- 23127231
TI  - Comparison between neoadjuvant and adjuvant gemcitabine plus cisplatin
      chemotherapy for muscle-invasive bladder cancer.
AB  - AIM: Radical cystectomy plus platinum-based perioperative chemotherapy is a
      standard treatment for patients with clinically localized muscle-invasive bladder
      cancer. The standard perioperative chemotherapy is methotrexate, vinblastine,
      doxorubicin and cisplatin (MVAC). However, no prospective randomized trial has
      been published that compares neoadjuvant and adjuvant chemotherapy for bladder
      cancer. Moreover, the efficacy of perioperative chemotherapy with gemcitabine
      plus cisplatin (GC) has not been clarified. In this study we have compared the
      clinical outcomes between neoadjuvant and adjuvant chemotherapy in patients
      receiving GC. METHODS: We retrospectively reviewed the records of patients who
      were scheduled to be treated with a radical cystectomy plus perioperative
      chemotherapy with GC from 2005 to 2010 at our institution. The primary outcome
      measure was recurrence-free survival (RFS). RESULTS: A total of 42 patients
      received perioperative chemotherapy with GC (25 neoadjuvant, 17 adjuvant). The
      median number of cycles of GC administered to the two groups was not
      significantly different. The median duration of follow up was 28.6 months. During
      the follow-up period, recurrence was observed in nine and three patients in the
      neoadjuvant and adjuvant groups, respectively. The RFS rate at median follow up
      was 67 and 76% in the neoadjuvant and adjuvant groups, respectively. No
      significant difference in RFS at median follow up was observed between the two
      groups (P = 0.124). CONCLUSION: Our results showed no statistically significant
      difference in RFS between neoadjuvant and adjuvant GC chemotherapy for muscle
      invasive bladder cancer. We expect to validate these findings in a prospective
      randomized trial.

PMID- 23127233
TI  - Medication administration by enrolled nurses: opinions of nurses in an Australian
      healthcare organization.
AB  - OBJECTIVE: This study examined the opinions of nurses about the introduction of
      enrolled nurse medication administration and analyzed its impact on the
      medication error rate. METHODS: Data were collected using a survey and
      examination of incident reports regarding nursing medication errors. Nurses
      (registered nurse, enrolled nurse with medication endorsement, enrolled nurse)
      responded to survey items regarding the introduction of enrolled nurse medication
      administration. Data analysis included descriptive statistics, Fischer's exact
      test, and chi-square analysis where appropriate. RESULTS: The majority of nurses
      (75.2%) supported enrolled nurse medication administration. However, differences
      in opinion were observed between registered nurse (RN) and enrolled nurse with
      medication endorsement (ENME) regarding clear understanding of responsibility and
      accountability (RN: 47.2% vs. ENME: 77.8%; p =.033), and whether suitable
      education was provided (RN: 34.7% vs. ENME: 73.7%; p =.012). Moreover, less than
      one-third of RNs agreed that the assessment process for EN medication endorsement
      clearly identified the competence of the ENME to administer medications.
      Nonetheless, nursing medication errors did not increase in the 12-month period
      after the introduction of enrolled nurse medication administration (pre: 314,
      post: 302). CONCLUSIONS: The findings of this study suggest areas that should be
      addressed in the future, including assessment of competence and focused education
      about accountability and responsibility.

PMID- 23127234
TI  - Clinical teleconferencing: bringing the patient to the classroom.
AB  - PROBLEM: The confidence to act on clinical judgment, ask for help, and juggle
      multiple competing priorities is best developed within a clinical setting.
      Traditional classroom learning, which is often static, does not support learning
      these skills or help new students learn how to "be" a nurse. Student nurses need
      frequent and repeated exposure to expert nurses and clinical environments.
      Traditional teaching methods may not be sufficient to meet these needs. METHOD:
      This project employs a strategy that supplies situated, context-driven learning
      with the aim of improving clinical reasoning by bringing real-world, real-time
      clinical scenarios into the classroom via audio conferencing. This classroom
      teaching strategy is based on the principles of learner-centered teaching, and
      the aim is to incorporate real-world clinical information into the classroom.
      Students are introduced to "real-time report" from special care areas as the
      basis for class activities and discussion. FINDINGS: Feedback on this model was
      sought through course evaluation data, focus groups with students, and
      participating nurses. NCLEX pass rate remained unchanged as a result of this
      teaching strategy. CONCLUSION: In this model, the classroom changes from being a
      physical place where knowledge is acquired to a place where knowledge is
      translated from and applied to practice.

PMID- 23127235
TI  - Creating a safe haven for employees who are victims of domestic violence.
AB  - PROBLEM: Intimate partner violence is a danger to American employers as well as
      costly for American businesses. BACKGROUND: Because one in four women is battered
      at some point in her lifetime and the percentage of employed women is over 50%,
      employers should address the issue of domestic violence at the workplace in an
      effort to keep employees safe while at work and to manage the financial burden
      that accompanies this problem. AIM: The author provides an overview of the
      problem and corresponding interventions that should be implemented to avoid
      violence in the workplace and to promote a culture of safety for all employees,
      particularly in a hospital setting.

PMID- 23127236
TI  - A concept analysis of self-efficacy among Chinese elderly with diabetes mellitus.
AB  - AIM: This paper is a report of concept analysis of self-efficacy in elderly with
      diabetes in China. METHODS: Literature was systematically retrieved from 2000 to
      2011 using five databases: Cumulative Index to Nursing and Allied Health
      Literature, MEDLINE, OVID, PsycInfo, and Web of Science. The key words used in
      the search were self-efficacy, diabetes, type 2, aged, self-care, and China. The
      electronic search was supplemented by a manual search of current issues of
      periodicals and follow-up of other cited materials, where appropriate. A total of
      45 articles were retrieved. After a careful review of the 45 articles most
      relevant to the topic, 31 articles remained. They were used to complete a concept
      analysis using Walker and Avant's technique. RESULTS: Four defining attributes of
      self-efficacy were identified: (a) cognitive recognition of requisite specific
      techniques and skills required to undertake diabetes self-management, (b)
      perceived expectations of the outcomes of self-management, (c) confidence in the
      capability to perform self-management, and (d) sustained efforts in self
      management of diabetes. CONCLUSIONS: Self-efficacy has been an important
      determinant in self-management among elderly with diabetes. The application of
      self-efficacy should be incorporated into decision-making and problem-solving
      procedures when caring for older adults with diabetes.

PMID- 23127237
TI  - International nursing exchange and collaboration with China: a perspective from
      the South and the East.
AB  - BACKGROUND: There are an imbalanced world power relationships and international
      knowledge system, as well as cultural differences across nations. RESULTS: Based
      on the author's international experiences, this article describes the needs and
      motivations of international exchange and collaboration in nursing from the
      perspective of both China and Western countries, examines the ethical and
      cultural issues involved, and suggests winning strategies. CONCLUSIONS: Western
      educators and scholars must keep these issues and strategies in mind in order to
      build a productive, mutually beneficial, and sustainable international exchanges
      and collaboration.

PMID- 23127238
TI  - A concept analysis about temporality and its applicability in nursing care.
AB  - TOPIC: Concept analysis of temporality. PURPOSE: To develop a comprehensive
      definition of temporality applicable to nursing care. SOURCE: Published
      literature. CONCLUSIONS: Temporality is a central component of our experience of
      the world. Phenomena such as the passage of time, time cycles, the trajectory of
      aging, transitions toward something, something being, and life as a limited time
      are integral to human experience. Temporality could be seen as lived time, and as
      such it is subjective time as opposed to clock time or objective time. The
      temporal dimensions of past, present, and future constitute the perspective of a
      person's temporal world.

PMID- 23127239
TI  - Perceptions of academic integrity among nursing students.
AB  - PURPOSE: Academic dishonesty is growing among nursing students. Reasons for this
      growth can be categorized into student, faculty, and system factors. Nursing
      faculty designed a study to explore this problem. CONCLUSIONS: We identified
      three themes: characteristics of students with academic integrity, patient
      safety, and professional outcomes. Exploring student perceptions of academic
      integrity can help faculty design measures to prevent dishonesty in these three
      areas. PRACTICE IMPLICATIONS: We recommend fostering culture change through
      strategies that target students, faculty, and systems. These strategies include
      peer mentoring, role modeling integrity, enhancing awareness of what constitutes
      cheating, and developing policies that promote honesty.

PMID- 23127240
TI  - Quality improvement in nursing: administrative mandate or professional
      responsibility?
AB  - For professionals, providing quality service and striving for excellence are
      ethical responsibilities. In many hospitals in the United States, however, there
      is evidence indicating that current quality improvement (QI) involving nurses is
      not always driven by their professional accountability and professional values.
      QI has become more an administrative mandate than an ethical standard for nurses.
      In this paper, the tension between QI as nurses' professional ethics and an
      administrative mandate will be described, and the implicit ideal-reality gap of
      QI will be examined. The threat to professional nursing posed by the current
      approach to QI will be examined, and ways to incorporate nursing professional
      values in a practical QI effort will be explored.

PMID- 23127241
TI  - Complexity leadership: a healthcare imperative.
AB  - PROBLEM: The healthcare system is plagued with increasing cost and poor quality
      outcomes. A major contributing factor for these issues is that outdated
      leadership practices, such as leader-centricity, linear thinking, and poor
      readiness for innovation, are being used in healthcare organizations. SOLUTION:
      Complexity leadership theory provides a new framework with which healthcare
      leaders may practice leadership. Complexity leadership theory conceptualizes
      leadership as a continual process that stems from collaboration, complex systems
      thinking, and innovation mindsets. CONCLUSION: Compared to transactional and
      transformational leadership concepts, complexity leadership practices hold
      promise to improve cost and quality in health care.

PMID- 23127242
TI  - Facilitating scholarly writer development: the writing scaffold.
AB  - PROBLEM OF INTEREST: Nursing faculty at a private, medium-sized university noted
      that students in their online Registered Nurse to Bachelor of Science in Nursing,
      hybrid Master of Science in Nursing, and online Doctor of Nursing Practice
      programs displayed varying scholarly writing abilities. PURPOSE: This article
      proposes an evidence-based comprehensive support framework, or scaffold that can
      be used in nursing education to facilitate the development of scholarly writing
      abilities in students. PRACTICE IMPLICATION: The writing scaffold is recommended
      for use by nursing faculty to facilitate the development of scholarly writing
      abilities within nursing, across nursing program levels, and across disciplines.

PMID- 23127243
TI  - When nurses become the "second" victim.
AB  - PURPOSE: Well-intentioned, conscientious nurses make medication errors. The
      subsequent feelings of guilt, remorse, and loss of personal and professional self
      esteem these nurses experience are well documented. In this paper, we analyze the
      concept of "second victim" within the context of medication administration
      errors. We also examine factors that contribute to nurses becoming second victims
      after making an error. PRACTICE IMPLICATIONS: Implications for nurses and nursing
      practice include nurses being given a greater degree of authority in designing
      the nursing work environment. Implications for nurses and nursing practice are
      presented. CONCLUSION: Further study is needed to more fully understand this
      phenomenon and to discover appropriate support mechanisms and interventions to
      minimize the harm to nurses.

PMID- 23127244
TI  - The 'Hygiene hypothesis' and the sharp gradient in the incidence of autoimmune
      and allergic diseases between Russian Karelia and Finland.
AB  - Autoimmune and allergic diseases have become a major health problem in the
      Western world during past decades. The hygiene hypothesis suggests that decreased
      microbial exposure in childhood leads to increasing prevalence of these diseases.
      This review summarizes epidemiological evidence and current immunological
      knowledge concerning the hygiene hypothesis. Recent results from Russian Karelia
      and Finland imply that environmental factors have greatly contributed to the
      increasing prevalence of immune-mediated disorders. Infections, or lack of them,
      may indeed be strongly involved in the development of both autoimmune and
      allergic diseases.

PMID- 23127245
TI  - Decreased activities of daily living is a strong risk factor for liver injury by
      anti-tuberculosis drugs.
AB  - BACKGROUND AND OBJECTIVE: We evaluated the association between activities of
      daily living and drug-induced liver injury by anti-tuberculosis drugs. METHODS:
      This retrospective cohort study included adult inpatients with newly diagnosed
      smear-positive lung tuberculosis treated with standard regimen in two hospitals.
      (n = 346; 63.6 +/- 20.3 years old; 106 (30.6%) females). Activities of daily
      living was divided into 'independent' (Barthel Index (BI) 80-100, 60.4%) and
      'decreased' (BI 0-75, 39.6%) categories. Liver injury was defined as the
      withdrawal or change of treatment regimen on the basis of the following criteria:
      serum transaminase concentrations were more than three times the upper limit of
      normal range with jaundice and/or hepatitis symptoms, or more than five times the
      upper limit of the normal range. RESULTS: Compared with 'independent' patients,
      patients with 'decreased' activities of daily living had odds ratios for liver
      injury of 4.2 (P < 0.001) in univariate analysis and 5.7 (P = 0.002) in logistic
      regression analysis after adjusting for other risk factors. CONCLUSIONS:
      Decreased activity of daily living is a strong risk factor for liver injury among
      adult inpatients with newly diagnosed smear-positive lung tuberculosis treated
      using a standard regimen.

PMID- 23127246
TI  - Xylem vulnerability to cavitation can be accurately characterised in species with
      long vessels using a centrifuge method.
AB  - Vulnerability to cavitation curves describe the decrease in xylem hydraulic
      conductivity as xylem pressure declines. Several techniques for constructing
      vulnerability curves use centrifugal force to induce negative xylem pressure in
      stem or root segments. Centrifuge vulnerability curves constructed for long
      vesselled species have been hypothesised to overestimate xylem vulnerability to
      cavitation due to increased vulnerability of vessels cut open at stem ends that
      extend to the middle or entirely through segments. We tested two key predictions
      of this hypothesis: (i) centrifugation induces greater embolism than dehydration
      in long-vesselled species, and (ii) the proportion of open vessels changes
      centrifuge vulnerability curves. Centrifuge and dehydration vulnerability curves
      were compared for a long- and short-vesselled species. The effect of open vessels
      was tested in four species by comparing centrifuge vulnerability curves for stems
      of two lengths. Centrifuge and dehydration vulnerability curves agreed well for
      the long- and short-vesselled species. Centrifuge vulnerability curves
      constructed using two stem lengths were similar. Also, the distribution of
      embolism along the length of centrifuged stems matched the theoretical pressure
      profile induced by centrifugation. We conclude that vulnerability to cavitation
      can be accurately characterised with vulnerability curves constructed using a
      centrifuge technique, even in long-vesselled species.

PMID- 23127247
TI  - Bradykinin type 2 receptor -9/-9 genotype is associated with triceps brachii
      muscle hypertrophy following strength training in young healthy men.
AB  - BACKGROUND: Bradykinin type 2 receptor (B2BRK) genotype was reported to be
      associated with changes in the left-ventricular mass as a response to aerobic
      training, as well as in the regulation of the skeletal muscle performance in both
      athletes and non-athletes. However, there are no reports on the effect of B2BRK 9
      bp polymorphism on the response of the skeletal muscle to strength training, and
      our aim was to determine the relationship between the B2BRK SNP and triceps
      brachii functional and morphological adaptation to programmed physical activity
      in young adults. METHODS: In this 6-week pretest-posttest exercise intervention
      study, twenty nine healthy young men (21.5 +/- 2.7 y, BMI 24.2 +/- 3.5 kg/m(2))
      were put on a 6-week exercise protocol using an isoacceleration dynamometer (5
      times a week, 5 daily sets with 10 maximal elbow extensions, 1 minute rest
      between sets). Triceps brachii muscle volumes were assessed by using magnetic
      resonance imaging before and after the strength training. Bradykinin type 2
      receptor 9 base pair polymorphism was determined for all participants. RESULTS:
      Following the elbow extensors training, an average increase in the volume of both
      triceps brachii was 5.4 +/- 3.4% (from 929.5 +/- 146.8 cm(3) pre-training to
      977.6 +/- 140.9 cm(3) after training, p<0.001). Triceps brachii volume increase
      was significantly larger in individuals homozygous for -9 allele compared to
      individuals with one or two +9 alleles (-9/-9, 8.5 +/- 3.8%; vs. -9/+9 and +9/+9
      combined, 4.7 +/- 4.5%, p < 0.05). Mean increases in endurance strength in
      response to training were 48.4 +/- 20.2%, but the increases were not dependent on
      B2BRK genotype (-9/-9, 50.2 +/- 19.2%; vs. -9/+9 and +9/+9 combined, 46.8 +/-
      20.7%, p > 0.05). CONCLUSIONS: We found that muscle morphological response to
      targeted training - hypertrophy - is related to polymorphisms of B2BRK. However,
      no significant influence of different B2BRK genotypes on functional muscle
      properties after strength training in young healthy non athletes was found. This
      finding could be relevant, not only in predicting individual muscle adaptation
      capacity to training or sarcopenia related to aging and inactivity, but also in
      determining new therapeutic strategies targeting genetic control of muscle
      function, especially for neuromuscular disorders that are characterized by
      progressive adverse changes in muscle quality, mass, strength and force
      production (e.g., muscular dystrophy, multiple sclerosis, Parkinson's disease).

PMID- 23127248
TI  - Activin receptor antagonists for cancer-related anemia and bone disease.
AB  - INTRODUCTION: Antagonists of activin receptor signaling may be beneficial for
      cancer-related anemia and bone disease caused by malignancies such as multiple
      myeloma and solid tumors. AREAS COVERED: We review evidence of dysregulated
      signaling by activin receptor pathways in anemia, myeloma-associated osteolysis,
      and metastatic bone disease, as well as potential involvement in carcinogenesis.
      We then review properties of activin receptor antagonists in clinical
      development. EXPERT OPINION: Sotatercept is a novel receptor fusion protein that
      functions as a soluble trap to sequester ligands of activin receptor type IIA
      (ActRIIA). Preclinically, the murine version of sotatercept increased red blood
      cells (RBC) in a model of chemotherapy-induced anemia, inhibited tumor growth and
      metastasis, and exerted anabolic effects on bone in diverse models of multiple
      myeloma. Clinically, sotatercept increases RBC markedly in healthy volunteers and
      patients with multiple myeloma. With a rapid onset of action differing from
      erythropoietin, sotatercept is in clinical development as a potential first-in
      class therapeutic for cancer-related anemia, including those characterized by
      ineffective erythropoiesis as in myelodysplastic syndromes. Anabolic bone
      activity in early clinical studies and potential antitumor effects make
      sotatercept a promising therapeutic candidate for multiple myeloma and malignant
      bone diseases. Antitumor activity has been observed preclinically with small
      molecule inhibitors of transforming growth factor-beta receptor type I (ALK5)
      that also antagonize the closely related activin receptors ALK4 and ALK7. LY
      2157299, the first such inhibitor to enter clinical studies, has shown an
      acceptable safety profile so far in patients with advanced cancer. Together,
      these data identify activin receptor antagonists as attractive therapeutic
      candidates for multiple diseases.

PMID- 23127249
TI  - Modeling the solubility of carbon dioxide in imidazolium-based ionic liquids with
      the PC-SAFT equation of state.
AB  - The goal of this work was to check the ability of the PC-SAFT equation to
      represent the solubility of carbon dioxide (CO(2)) in ionic liquids. Parameters
      of pure imidazolium-based ionic liquids were estimated using experimental
      densities over a large range of temperatures and then correlated with respect to
      the molecular weight and structure of the solvents. It was found that such a
      correlation is able to predict the density with high accuracy. The solubility of
      carbon dioxide in such ionic liquids was then studied. The binary interaction
      parameter k(ij) needed for the representation of such binary systems was first
      fitted to experimental liquid-vapor equilibria data. In a second step, a
      correlation based on the group contribution concept was developed to determine
      this temperature-dependent parameter. The ability of the model to describe
      accurately carbon dioxide solubility in imidazolium-based ionic liquids is
      demonstrated.

PMID- 23127250
TI  - Effects of molecular size and surface hydrophobicity on oligonucleotide
      interfacial dynamics.
AB  - Single-molecule total internal reflection fluorescence microscopy was used to
      observe the dynamic behavior of polycytosine single-stranded DNA (ssDNA) (1-50
      nucleotides long) at the interface between aqueous solution and hydrophilic
      (oligoethylene glycol-modified fused silica, OEG) and hydrophobic
      (octadecyltriethoxysilane-modified fused silica, OTES) solid surfaces. High
      throughput molecular tracking was used to determine >75,000 molecular
      trajectories for each molecular length, which were then used to calculate surface
      residence time and squared displacement (i.e., "step-size") distributions. On
      hydrophilic OEG surfaces, the surface residence time increased systematically
      with ssDNA chain length, as expected due to increasing molecule-surface
      interactions. Interestingly, the residence time decreased with increasing ssDNA
      length on the hydrophobic OTES surface, particularly for longer chains.
      Similarly, the interfacial mobility of polynucleotides slowed with increasing
      chain length on OEG, but became faster on OTES. On OTES surfaces, the rates
      associated with desorption and surface diffusion exhibited the distinctive
      anomalous temperature dependence that is characteristic of hydrophobic
      interactions for short-chain species but not for longer chains. These combined
      observations suggest that long oligonucleotides adopt conformations minimizing
      hydrophobic interactions, e.g., by internal sequestration of hydrophobic
      nucleobases.

PMID- 23127251
TI  - Effect of autologous platelet-rich plasma-releasate on intervertebral disc
      degeneration in the rabbit anular puncture model: a preclinical study.
AB  - INTRODUCTION: Platelet-rich plasma (PRP) is a fraction of plasma in which several
      growth factors are concentrated at high levels. The active soluble releasate
      isolated following platelet activation of PRP (PRP-releasate) has been
      demonstrated to stimulate the metabolism of IVD cells in vitro. The in vivo
      effect of PRP-releasate on degenerated IVD remains unknown. The purpose of this
      study was to determine the reparative effects of autologous PRP-releasate on
      degenerated intervertebral discs (IVDs). METHODS: To induce disc degeneration,
      New Zealand white rabbits (n = 12) received anular puncture in two noncontiguous
      discs. Autologous PRP and PPP (platelet-poor plasma) were isolated from fresh
      blood using two centrifugation techniques. Four weeks after the initial puncture,
      releasate isolated from clotted PPP or PRP (PPP- or PRP-releasate), or phosphate
      buffered saline (PBS; control) was injected into the punctured discs. Disc
      height, magnetic resonance imaging (MRI) T2-mapping and histology were assessed.
      RESULTS: Anular puncture produced a consistent disc narrowing within four weeks.
      PRP-releasate induced a statistically significant restoration of disc height (PRP
      vs. PPP and PBS, P<0.05). In T2-quantification, the mean T2-values of the nucleus
      pulposus (NP) and anulus fibrosus (AF) of the discs were not significantly
      different among the three treatment groups. Histologically, the number of
      chondrocyte-like cells was significantly higher in the discs injected with PRP
      releasate compared to that with PBS. CONCLUSIONS: The administration of active
      PRP-releasate induced a reparative effect on rabbit degenerated IVDs. The results
      of this study suggest that the use of autologous PRP-releasate is safe and can
      lead to a clinical application for IVD degeneration.

PMID- 23127253
TI  - Large-scale synthesis and self-organization of silver nanoparticles with Tween 80
      as a reductant and stabilizer.
AB  - Tween 80 (polysorbate 80) has been used as a reducing agent and protecting agent
      to prepare stable water-soluble silver nanoparticles on a large scale through a
      one-pot process, which is simple and environmentally friendly. Silver ions can
      accelerate the oxidation of Tween 80 and then get reduced in the reaction
      process. The well-ordered arrays such as ribbon-like silver nanostructures could
      be obtained by adjusting the reaction conditions. High-resolution transmission
      electron microscopy confirms that ribbon-like silver nanostructures
      (approximately 50 nm in length and approximately 2 MUm in width) are composed of
      a large number of silver nanocrystals with a size range of 2 to 3 nm. In
      addition, negative absorbance around 320 nm in the UV-visible spectra of silver
      nanoparticles has been observed, probably owing to the instability of nanosized
      silver colloids.

PMID- 23127254
TI  - Synthesis of spiropiperidine lactam acetyl-CoA carboxylase inhibitors.
AB  - The synthesis of 4',6'-dihydrospiro[piperidine-4,5'-pyrazolo[3,4-c]pyridin]
      7'(2'H)-one-based acetyl-CoA carboxylase inhibitors is reported. The hitherto
      unknown N-2 tert-butyl pyrazolospirolactam core was synthesized from ethyl 3
      amino-1H-pyrazole-4-carboxylate in a streamlined 10-step synthesis requiring only
      one chromatography procedure. The described synthetic strategy provides pyrazolo
      fused spirolactams from halogenated benzylic arenes and cyclic carboxylates. Key
      steps include a regioselective pyrazole alkylation providing the N-2 tert-butyl
      pyrazole and a Curtius rearrangement under both conventional and flow conditions
      to install the hindered amine via a stable and isolable isocyanate. Finally, a
      Parham-type cyclization was used to furnish the desired spirolactam. An analogous
      route provided efficient access to the related N-1 isopropyl lactam series.
      Elaboration of the lactam cores via amidation enabled synthesis of novel ACC
      inhibitors and the identification of potent analogues.

PMID- 23127256
TI  - A quantitative analysis of torn and cut duct tape physical end matching.
AB  - Forensic scientists are often asked to physically compare duct tape samples found
      in association with criminal activity. This study was designed to statistically
      evaluate the error and accuracy rates associated with duct tape physical end
      matching. The experimental design consisted of a blind study in which three
      researchers independently analyzed eight types of tape subjected to four methods
      of separation. The lowest mean accuracy observed was 98.15%, the highest mean
      false-positive rate observed was 3.33%, and the highest mean false-negative rate
      was 2.67%. Overall, high accuracy with low false-positive and false-negative
      error rates were observed. This study confirms the use of physical end matching
      in identifying duct tape samples as matching or nonmatching and that the
      differences between analysts, brands, tape grades, tape color, and methods of
      separation have varying contributions to misidentifications and inconclusive
      results. This study also demonstrates the importance of peer review in duct tape
      analysis.

PMID- 23127255
TI  - The palmitoylation state of PMP22 modulates epithelial cell morphology and
      migration.
AB  - PMP22 (peripheral myelin protein 22), also known as GAS 3 (growth-arrest-specific
      protein 3), is a disease-linked tetraspan glycoprotein of peripheral nerve myelin
      and constituent of intercellular junctions in epithelia. To date, our knowledge
      of the post-translational modification of PMP22 is limited. Using the CSS-Palm
      2.0 software we predicted that C85 (cysteine 85), a highly conserved amino acid
      located between the second and third transmembrane domains, is a potential site
      for palmitoylation. To test this, we mutated C85S (C85 to serine) and established
      stable cells lines expressing the WT (wild-type) or the C85S-PMP22. In Schwann
      and MDCK (Madin-Darby canine kidney) cells mutating C85 blocked the
      palmitoylation of PMP22, which we monitored using 17-ODYA (17-octadecynoic acid).
      While palmitoylation was not necessary for processing the newly synthesized PMP22
      through the secretory pathway, overexpression of C85S-PMP22 led to pronounced
      cell spreading and uneven monolayer thinning. To further investigate the
      functional significance of palmitoylated PMP22, we evaluated MDCK cell migration
      in a wound-healing assay. While WT-PMP22 expressing cells were resistant to
      migration, C85S cells displayed lamellipodial protrusions and migrated at a
      similar rate to vector control. These findings indicate that palmitoylation of
      PMP22 at C85 is critical for the role of the protein in modulating epithelial
      cell shape and motility.

PMID- 23127257
TI  - Synthesis, crystal structures, and dual donor luminescence sensitization in novel
      terbium tetracyanoplatinates.
AB  - A series of novel terbium tetracyanoplatinate compounds all incorporating
      tridentate 2,2':6'2"-terpyridine (terpy) or 4'-chloro-2,2':6'2"-terpyridine
      (terpy-Cl) were synthesized and used to investigate the phenomenon of dual-donor
      sensitization of Tb(3+). Judicious choice of the Tb(3+) salt and reaction
      conditions results in the isolation of {Tb(terpy)(H2O)2(NO3)Pt(CN)4}.CH3CN (1A),
      {Tb(terpy)(H2O)2(NO3)Pt(CN)4}.3.5H2O (1B), {Tb(terpy
      Cl)(H2O)2(NO3)Pt(CN)4}.2.5H2O (2), [Tb(terpy)(H2O)2(CH3COO)2]2Pt(CN)4.4H2O (3),
      or [Tb2(terpy)2(H2O)2(CH3COO)5]2Pt(CN)4.7H2O (4). The compounds 1A, 1B, and 2
      contain one-dimensional polymeric structures with bridging of
      [Tb(L)(NO3)(H2O)2](2+) (L = terpy or terpy-Cl) moieties by cis-bridging
      tetracyanoplatinate (TCP) anions as determined via single-crystal X-ray
      diffraction studies. Both 3 and 4, however, contain Tb(3+) coordinated by
      multiple acetate ligands and terpy, but not TCP, and are classified as zero
      dimensional complex salts. Platinophilic interactions that dominate
      tetracyanoplatinate structural chemistry are present in the form of dimeric units
      in the polymeric compounds, but are totally absent in 3 and 4. The structural
      differences result in markedly different luminescence properties for the two
      classes of compounds. All of the polymeric compounds display efficient donor
      acceptor intramolecular energy transfer (IET) from the terpy unit to the Tb(3+)
      ion. Although the TCP units are also directly coordinated to the Tb(3+) ion in
      the three polymers, only in 1B and 2 are the Pt...Pt interactions strong enough
      to provide MMLCT bands of appropriate energy to result in a dual-donor effect to
      the Tb(3+) sensitization. Even in these cases, TCP does not efficiently sensitize
      the Tb(3+), rather a broad band TCP emission results. However, terpy and acetate
      ligands are bonded directly to the Tb(3+) ion in 3 and 4 and provide a strong
      dual-donor sensitization effect as evidenced by the large QY for Tb(3+). 

PMID- 23127258
TI  - Helminth communities of fish as ecological indicators of lake health.
AB  - This paper deals largely with the dynamics and changes in the helminth parasite
      communities of fish along the trophic gradient of lakes. The use of
      parasitological community data as a bioindicator of environmental health
      underlines the need to study parasite communities at comparable localities with
      known pollution levels. The comparison of the conditions in different habitats
      might be helpful to differentiate between normal fluctuations in ambient
      conditions and pollution-mediated effects. Therefore, the present study was
      designed to examine the community structure of parasites in snow trout
      (Schizothorax niger Heckel) inhabiting 3 lakes of contrasting trophic status in
      Kashmir. The idea of selecting the lakes, namely Anchar (strongly
      hypereutrophic), Dal (eutrophic) and Manasbal (mesotrophic) for this study was
      intentional as they depict different trophic gradients and exhibit the desirable
      pattern which was a prerequisite for this study. The findings presented in this
      article suggest an apparent lake-wise gradient in community structure, as the
      increase in trematode and cestode infections in Anchar was markedly greater, to
      levels clearly distinguishable from those in the other two water bodies. We
      conclude that human-induced eutrophication of lakes modifies the parasite
      community at component level and community-level studies on parasites may provide
      information on health status of lakes.

PMID- 23127259
TI  - Electrical status epilepticus in sleep: clinical presentation and
      pathophysiology.
AB  - Electrical status epilepticus in sleep involves an electroencephalographic
      pattern where interictal epileptiform activity is potentiated in the transition
      from wakefulness to sleep. Near-continuous spikes and waves that occupy a
      significant proportion of nonrapid eye movement sleep appear as a result of sleep
      potentiated epileptiform activity. This electroencephalographic pattern appears
      in different electroclinical syndromes that present three common characteristics
      with different degrees of severity: seizures, sleep-potentiated epileptiform
      activity, and neuropsychologic regression. Continuous spikes and waves during
      sleep comprise the severest epileptic encephalopathy in the electroclinical
      spectrum. Landau-Kleffner syndrome presents with intermediate severity. Some
      "benign" pediatric focal epileptic syndromes represent the mildest end of this
      continuum. Based on published data, we provide a framework for clinical and
      electrical events. The underlying mechanisms leading to sleep potentiation of
      epileptiform activity in electrical status epilepticus in sleep are incompletely
      understood. A genetic basis or acquired early developmental insult may disrupt
      the normal maturation of neuronal networks. These factors may dynamically alter
      normal processes of brain development, leading to an age-related pattern of
      electroclinical expression of electrical status epilepticus in sleep.

PMID- 23127260
TI  - Peripartum consultations expand the role of the fetal/neonatal neurologist.
AB  - The peripartum period entails the next prenatal interval when novel
      neuroprotective strategies will be designed and tested. Research development will
      lead to novel evaluations for maternal-fetal pairs who require inpatient
      treatment and possible delivery for worsening or acute neurologic problems.
      Future studies should critically compare serial fetal surveillance assessments
      with postnatal clinical findings to detect and treat more accurately
      fetal/neonatal brain disorders that begin or worsen during the peripartum period.
      Clinical management decisions require an interdisciplinary treatment approach.
      Protocols may begin before and during parturition, and continue through neonatal
      resuscitation and early postnatal periods into infancy. Appropriate choices of
      preventive, rescue, and repair neuroprotective interventions must consider both
      the timing and etiologies of encephalopathies in the context of maternal, fetal,
      placental, and neonatal diseases.

PMID- 23127261
TI  - Metabolic effects of aripiprazole and pimozide in children with Tourette
      syndrome.
AB  - This study assessed the metabolic effects of aripiprazole and pimozide in
      pediatric Tourette syndrome, a neurodevelopmental condition characterized by
      multiple motor and phonic tics. Patients receiving aripiprazole (n = 25) or
      pimozide (n = 25) were compared with medication-free patients (n = 25). Body mass
      index, glycemia, triglyceridemia, and cholesterolemia were monitored at baseline
      and 12 and 24 months after commencing treatment. The aripiprazole group
      demonstrated significant increases in cholesterolemia. The pimozide group
      demonstrated significant increases in glycemia. Both groups demonstrated
      elevations in triglyceridemia not significantly different from those in
      unmedicated control subjects. The effect of aripiprazole on cholesterol was
      apparent after 12 months, but leveled off during year 2 of treatment.
      Longitudinal studies are required to evaluate the full extent of glycemic
      alterations with pimozide. Both agents appear relatively safe for use in
      pediatric Tourette syndrome. These findings will help guide medication selection
      in patients with specific medical vulnerabilities.

PMID- 23127262
TI  - Evaluation of appetite-stimulating hormones in prepubertal children with epilepsy
      during topiramate treatment.
AB  - We investigated the mechanism of topiramate-related appetite loss and exposed its
      relationship to body weight, body mass index, body fat index, and serum insulin,
      lipid, leptin, neuropeptide-Y, cortisol, ghrelin, and adiponectin levels. Twenty
      children with epilepsy were evaluated at baseline and months 3 and 6 of
      treatment. Their body fat index, leptin, and neuropeptide-Y levels significantly
      decreased at month 3, whereas significant decreases occurred in body weight, body
      mass index, body fat index, neuropeptide-Y, cholesterol, and cortisol levels of
      patients at month 6 compared with baseline. Weight loss during topiramate
      treatment was attributed to loss of appetite and reduced food intake caused by
      reductions in neuropeptide-Y. To the best of our knowledge, this study is the
      first to describe reductions in neuropeptide-Y with topiramate use in humans.

PMID- 23127263
TI  - Lamotrigine serum concentration in children with epilepsy.
AB  - The correlation between lamotrigine serum concentration, efficacy, and toxicity
      in children is controversial. The database of the Clinical Pharmacology
      Laboratory at Assaf Harofeh Medical Center was retrospectively searched to
      identify lamotrigine serum concentrations in children aged 2-19 years with
      refractory epilepsy who received lamotrigine as monotherapy or polytherapy from
      2007-2010. Data collected included age at epilepsy onset, additional
      antiepileptic drugs, lamotrigine dose, monthly seizure frequency before and after
      lamotrigine treatment, and side effects. Sixty blood samples were collected from
      42 children aged 10.1 +/- 4.9 years (range, 2-20 years). Seizure types included
      complex partial (n = 28), simple partial (n = 7), absence (n = 2), and
      generalized tonic-clonic (n = 23). Decreased seizure frequency was observed in 38
      (63.3%) patients. No correlation with lamotrigine serum concentration was
      evident, but seizure frequency was significantly influenced by age and
      lamotrigine dose. Side effects were reported in 21 (35%) patients. Only diplopia
      was significantly correlated with lamotrigine serum concentration. Lamotrigine
      was more effective at lower doses and in older children. Lamotrigine serum
      concentration correlated significantly with diplopia, but not with other side
      effects or with clinical efficacy. Overall, lamotrigine is effective and safe in
      children with refractory epilepsy.

PMID- 23127264
TI  - What is the worst part about having epilepsy? A children's and parents'
      perspective.
AB  - Do children and parents view epilepsy similarly? Children and their parents at an
      epilepsy camp received a voluntary survey. Twenty children (aged 9-15 years) and
      their parents responded. Fifty percent of children and 27% of parents thought
      social stigmatization comprised the worst part of having epilepsy, whereas 38%
      and 40%, respectively, chose physical seizures. Over half of children and parents
      would want to have fewer or no seizures if they could change one thing. Sixty
      seven percent of children and 93% of parents agreed that epilepsy camp was fun,
      and the other third of children considered it a place where they felt normal.
      Overall, children with epilepsy and their parents agreed. Despite the morbidities
      and potential risks of seizures and of the treatments themselves, the majority of
      children were most concerned with the stigma attached to having epilepsy.

PMID- 23127265
TI  - Predisposing factors of posterior reversible encephalopathy syndrome in acute
      childhood leukemia.
AB  - A retrospective chart review was performed on 19 patients aged <18 years who
      developed posterior reversible encephalopathy syndrome as a complication during
      treatment of acute childhood leukemia. Posterior reversible encephalopathy
      syndrome was most often observed during acute lymphoblastic leukemia induction
      chemotherapy (n = 9, 47.4%) and after hematopoietic stem cell transplantation (n
      = 8, 42.1%). Among eight patients with the complication of posterior reversible
      encephalopathy syndrome after hematopoietic stem cell transplantation, five
      (62.5%) had a history of hypertension. In contrast, among 11 patients with the
      complication of posterior reversible encephalopathy syndrome without
      hematopoietic stem cell transplantation, only one (9.1%) had a history of
      hypertension. Moreover, unlike other leukemia induction chemotherapy, posterior
      reversible encephalopathy syndrome developed only in patients who received acute
      lymphoblastic leukemia induction chemotherapy. Posterior reversible
      encephalopathy syndrome patients required long-term anticonvulsant therapy (n =
      9, 50.0%) and manifested intractable seizures (n = 3, 16.7%). Sequelae were
      evident in long-term follow-up magnetic resonance images (n = 5, 26.3%). Acute
      lymphoblastic leukemia chemotherapy regimens apparently comprised the main
      predisposing factors for posterior reversible encephalopathy syndrome complicated
      during induction chemotherapy, compared with hypertension and immunosuppressive
      agents after hematopoietic stem cell transplantation.

PMID- 23127266
TI  - Perinatal occipital lobe injury in children: analysis of twenty-one cases.
AB  - This study used magnetic resonance imaging to analyze causes and clinical courses
      of pediatric occipital lobe injury. Patients undergoing magnetic resonance
      imaging for suspected bilateral occipital lobe injury at our Neurodevelopmental
      Department between July 2007 and June 2011 were included. We evaluated magnetic
      resonance imaging characteristics, clinical courses, electroencephalogram
      monitoring, and Denver Development Screen Test scores. Twenty-one infants were
      examined. Of these, 10 had been born preterm. Thirteen patients demonstrated
      hypoglycemia. Perinatal period hypoglycemia comprised the most common cause
      (71.4%) of occipital brain injury. Visual abnormalities were evident in 18
      patients. Seventeen (80.9%) patients manifested epilepsy. Infantile spasms were
      observed in 13 cases (76.5%). According to Denver Development Screen Test
      assessment, 17 patients demonstrated delayed motor development. Motor function
      and language improved in 10 patients after effective control of their seizures.
      Hypoglycemia constitutes the most common cause of occipital injury in infants.
      Visual impairment, startle episodes, infantile spasms, and motor developmental
      delay comprise the most common complications, whereas language function is
      usually spared.

PMID- 23127267
TI  - Therapeutic hypothermia for febrile infection-related epilepsy syndrome in two
      patients.
AB  - Despite advances in critical care, febrile infection-related epilepsy syndrome
      remains the most important cause of mortality and neurologic deficits during
      childhood. Only a few therapeutic agents were reported to shorten the acute phase
      and improve outcomes. Therapeutic hypothermia was reported effective in
      stabilizing immune activation, brain edema, and seizure activity, to protect the
      brain from ongoing functional, apoptotic neural, and glial damage and the
      systemic expansion of the cytokine storm. We present two pediatric cases of
      febrile infection-related epilepsy syndrome, refractory to conventional medical
      therapy. Moderate therapeutic hypothermia at 33 degrees C resulted in fast,
      sustained control of refractory status epilepticus. After 3 months, both patients
      recovered with a Glasgow Outcome Scale score of 4. Therapeutic hypothermia may
      play an important role in children with febrile infection-related epilepsy
      syndrome.

PMID- 23127268
TI  - Brain abscess from a peritonsillar abscess in an immunocompetent child: a case
      report and review of the literature.
AB  - A brain abscess is uncommon but potentially lethal. Common predisposing risk
      factors include congenital cyanotic heart disease, immunocompromised status, and
      the presence of septic foci. We describe a left frontal brain abscess accompanied
      by fever, headache, and weight loss for a 3-month period. The presumptive source
      of the brain abscess involved a left peritonsillar abscess. To the best of our
      knowledge, one similar case was reported in the literature in 1929. The specific
      signs of peritonsillar abscess in our patient included trismus, decreased
      phonation, and a muffled voice. The peritonsillar abscess was not clinically
      diagnosed, but incidentally detected on lower axial sections of cranial magnetic
      resonance imaging. Fever and trismus improved after surgical drainage of the
      peritonsillar abscess. The cerebral abscess was conservatively treated with
      intravenous antibiotics. The patient developed hydrocephalus as a sequela to the
      involvement of the basal meninges.

PMID- 23127269
TI  - Intraparenchymal hemorrhage in a neonate with cleidocranial dysostosis.
AB  - We present a case of intraparenchymal hemorrhage in a neonate with cleidocranial
      dysostosis, a skeletal dysplasia that leads to delayed skull ossification. The
      patient's details are reported, including neuroimaging, photographs of classic
      dysmorphic features, and genetic testing. After spontaneous vaginal birth, the
      patient was hypotonic and encephalopathic, with unusually large and boggy
      fontanelles. No palpable bone overlay his bilateral temporal lobes, and his
      facial features were multiply dysmorphic. The patient's father exhibited similar
      facial features and congenital absence of the right clavicle, suggesting
      cleidocranial dysostosis. Magnetic resonance imaging at age 4 days confirmed a
      large right temporal lobe intraparenchymal hemorrhage, with extensive
      subarachnoid hemorrhage overlying both temporal and parietal lobes. A clinical
      diagnosis of cleidocranial dysostosis was confirmed by testing of the RUNX2 gene,
      which revealed a novel sequence alteration predicted to be disease-causing. Given
      that no palpable bone overlay the location of brain hemorrhage, and no other
      cause for hemorrhage was identified, we attribute the temporal lobe hemorrhage to
      forces on the skull incurred during normal vaginal delivery in the setting of
      decreased skull ossification.

PMID- 23127270
TI  - Pediatric cefepime neurotoxicity.
AB  - Cefepime toxicity is characterized by altered mental status, confusion, and
      decreased responsiveness. We describe a 14-year-old girl who developed acute
      encephalopathy associated with supratherapeutic cefepime concentrations in the
      setting of acute renal failure. The authors were unable to identify any previous
      reports of this occurrence in a child.

PMID- 23127271
TI  - Enzyme replacement therapy in an attenuated case of mucopolysaccharidosis type I
      (Scheie syndrome): a 6.5-year detailed follow-up.
AB  - We present the 6.5-year follow-up of a boy with Scheie syndrome whose therapy was
      initiated at age 2.5 years. Detailed anthropometric features, echocardiography,
      ophthalmologic and audiologic examinations, psychologic tests, joint range of
      motion, skeletal radiographs, ultrasound studies of liver and spleen volumes,
      urinary glycosaminoglycans, and antibodies were documented. After 6.5 years of
      enzyme replacement therapy, the patient experienced a decline in overall status,
      and the disease progressed significantly despite treatment. The patient's height
      at age 9 was equal to that at age 6. The patient developed heart insufficiency
      and a deterioration of airway flow. The patient's intelligence quotient remained
      unchanged, i.e., at the average level of 86 on the Terman-Merill Scale. Magnetic
      resonance imaging revealed cervical spinal canal stenosis and marked spinal cord
      compression with myelopathy. A worsening of carpal tunnel syndrome was also
      evident. Ophthalmologic evaluation revealed increased central corneal thickness
      and intraocular pressure. In audiologic assessment, the patient's results were
      similar to those after 3 years of treatment. The only benefit involved
      temporarily improved passive and active shoulder flexion. Overall, the benefit of
      enzyme replacement therapy with laronidase on Scheie syndrome appeared minimal.

PMID- 23127272
TI  - Neonatal neurocritical care: overlooked neurologic syndromes.
AB  - Although encephalopathy, seizures, and changes in tone comprise the most common
      signs of neurologic disruption in neonates (and in older children and adults),
      careful neurologic examination can yield additional clues to assist with the
      management of underlying neurologic conditions.

PMID- 23127273
TI  - Establishment of automated culture system for murine induced pluripotent stem
      cells.
AB  - BACKGROUND: Induced pluripotent stem (iPS) cells can differentiate into any cell
      type, which makes them an attractive resource in fields such as regenerative
      medicine, drug screening, or in vitro toxicology. The most important prerequisite
      for these industrial applications is stable supply and uniform quality of iPS
      cells. Variation in quality largely results from differences in handling skills
      between operators in laboratories. To minimize these differences, establishment
      of an automated iPS cell culture system is necessary. RESULTS: We developed a
      standardized mouse iPS cell maintenance culture, using an automated cell culture
      system housed in a CO2 incubator commonly used in many laboratories. The iPS
      cells propagated in a chamber uniquely designed for automated culture and showed
      specific colony morphology, as for manual culture. A cell detachment device in
      the system passaged iPS cells automatically by dispersing colonies to single
      cells. In addition, iPS cells were passaged without any change in colony
      morphology or expression of undifferentiated stem cell markers during the 4 weeks
      of automated culture. CONCLUSIONS: Our results show that use of this compact,
      automated cell culture system facilitates stable iPS cell culture without obvious
      effects on iPS cell pluripotency or colony-forming ability. The feasibility of
      iPS cell culture automation may greatly facilitate the use of this versatile cell
      source for a variety of biomedical applications.

PMID- 23127274
TI  - Small sizes of TiO2-NPs exhibit adverse effects at predicted environmental
      relevant concentrations on nematodes in a modified chronic toxicity assay system.
AB  - In Caenorhabditis elegans, although acute toxicity of TiO(2) nanoparticles
      (TiO(2)-NPs) at high concentrations has been investigated, we still know little
      about chronic toxicity of TiO(2)-NPs. Our data here showed that acute TiO(2)-NPs
      exposure in the range of MUg/L had no obviously adverse effects on nematodes, but
      the chronic toxicities of large sizes (60 nm and 90 nm) of TiO(2)-NPs in the
      range of MUg/L were detected in nematodes in a modified chronic toxicity assay
      system. Moreover, chronic toxicities of small sizes (4 nm and 10nm) of TiO(2)-NPs
      in the range of ng/L were observed in nematodes with locomotion behavior and ROS
      production as endpoints. In nematodes chronically exposed to small sizes of
      TiO(2)-NPs at predicted environmental relevant concentrations, locomotion
      behavior was significantly (P<0.01) correlated with ROS production. Furthermore,
      treatment with antioxidants (ascorbate and N-acetyl-l-cysteine) inhibited both
      the induction of ROS production and the decrease of locomotion behaviors observed
      in nematodes chronically exposed to small sizes of TiO(2)-NPs at predicted
      environmental relevant concentrations. Therefore, chronic exposure to small sizes
      of TiO(2)-NPs at predicted environmental relevant concentrations can cause
      adverse effects on nematodes, and formation of such adverse effects may be
      largely due to the induction of oxidative stress.

PMID- 23127275
TI  - Composting of waste paint sludge containing melamine resin and the compost's
      effect on vegetable growth and soil water quality.
AB  - Melamine resin (MR) is introduced to the environment from many industrial
      effluents, including waste paint sludge (WPS) from the automobile industry.
      Melamine resin contains a high nitrogen (N) content and is a potential N source
      during composting. In this study, two carbon sources, waste paper (WP) and plant
      residue (PR), were used to study their effects on composting of WPS. Additional
      work tested the WPS-composts effects on plant growth and soil water quality.
      After 84 days of composting, 85% and 54% of the initial MR was degraded in WP-
      and PR-composts, respectively. The limiting factor was that the MR created clumps
      during composting so that decomposition was slowed. Compared to the untreated
      control, both WP- and PR-composts increased growth of cucumber (Cucumis sativus),
      radish (Raphanus sativus) and lettuce (Lactuca sativa). Concentrations of trace
      elements in plants and soil water did not rise to a level that would preclude WPS
      composts from being used as a soil amendment.

PMID- 23127276
TI  - Application of pyrolysis process to remove and recover liquid crystal and films
      from waste liquid crystal display glass.
AB  - Liquid crystal display (LCD) glass mainly consists of polarizing film, liquid
      crystal and glass substrate. Removing and recovering the liquid crystal and films
      from the LCD glass effectively has important significance for recovering the
      other parts. This study proposed a pyrolysis process to recover the organic parts
      from LCD glass. Through thermal gravimetric analysis, the pyrolysis temperature
      of the LCD glass could be chosen at 850 K. The removal rate of organic parts from
      LCD glass reached 87.87 wt%. Pyrolysis products consisted of 66.82 wt% oils,
      21.01 wt% gaseous and 12.13 wt% residues. In addition, the oils contained 46.27
      wt% acetic acid and 32.94 wt% triphenyl phosphate. Then, the pyrolysis mechanisms
      and products sources of the liquid crystal glass have been analyzed based on the
      information of bonds energy. The pyrolysis mechanism analysis proved that the
      products mainly consisted of acetic acid, triphenyl phosphate and C, which is
      consistent to the results of GC-MS analysis. A reasonable way has been put
      forward to recycle the pyrolysis products: acetic acid and triphenyl phosphate
      can be collected by distillation, the rest oils and gases can be used as fuel and
      the remained glass can be used to extract indium and to produce building
      materials.

PMID- 23127277
TI  - Evaluation of EROD and CYP3A4 activities in earthworm Eisenia fetida as
      biomarkers for soil heavy metal contamination.
AB  - In this study, the effects of heavy metals (Cd, Cu, Pb, Zn) on EROD and CYP3A4
      activities in the earthworm Eisenia fetida were evaluated to find out their
      possible induction and potential as biomarkers for soil heavy metal
      contamination. The earthworms were exposed to increasing concentrations of Cd
      (0.1-8 mg L(-1)), Cu (10-200 mg L(-1)), Pb (20-400 mg L(-1)) or Zn (50-400 mg L(
      1)) in filter papers for 48 h. EROD activity was significantly changed in dose
      dependent manners after exposure to each of the four metals. CYP3A4 activity was
      significantly induced by Cd and Pb, rather by Cu and Zn. This is the first report
      on heavy metal-induced changes of CYP3A4 activity in earthworms. Among the four
      heavy metals, Cd was the most potent inducing EROD and CYP3A4. While EROD and
      CYP3A4 activities showed a similar trend, EROD is more sensitive than CYP3A4
      activity in E. fetida as a biomarker for heavy metals pollution.

PMID- 23127278
TI  - Immunohistochemical study of pElk-1 expression in human breast cancer:
      association with breast cancer biologic profile and clinicopathologic features.
AB  - BACKGROUND: Recently an increased interest on Elk1 protein and its role in breast
      cancer evolution has been noted. This protein is an element of the Ets family of
      transcription factors and it has been involved in a number of important cell
      processes through the activation of different genes, in a number of normal
      tissues as well as in many malignancies. METHODS: One hundred and seventy (n =
      170) cases of operable breast cancer (invasive ductal, lobular and mixed type
      breast carcinomas) were randomly selected and investigated for the expression of
      pElk-1, Ki-67 and Cyclin D1 using immunohistochemistry. Our findings were
      correlated with tumors' clinicopathologic data and biologic profile. RESULTS:
      Activated Elk1 is positively associated with ER (p-value: 0.018) and also shows a
      positive association of with Cyclin D1 (p-value: <0.001). No relationship was
      noted between pElk1 and Ki67 (p-value: 0.213). Luminal A and B Her-2 negative
      breast cancer subtypes were showing greater pElk-1 immunoreactivity compared to
      Her-2 and Basal breast cancer subtypes, and also a higher staining intensity. No
      association of the molecule with other clinicopathologic characteristics (tumor
      size, stage, histological type or lymph node metastases) or disease adverse
      events (local recurrence, metastasis or death) was evidenced. CONCLUSIONS: Our
      findings offer a new perspective for the role of pElk-1 in breast neoplasia
      suggesting a direct relation of this molecule to tumor biology and a putative
      target of personalized breast cancer therapies, although its
      prognostic/discriminant role is not supported.

PMID- 23127279
TI  - Accelerated partial breast irradiation: the need for well-defined patient
      selection criteria, improved volume definitions, close follow-up and discussion
      of salvage treatment.
AB  - Breast-conserving therapy, including whole breast irradiation, has become a well
      established alternative to mastectomy in early-stage breast cancer patients, with
      similar survival rates and better cosmetic outcome. However, many women are still
      treated with mastectomy, due to logistical issues related to the long course of
      radiotherapy (RT). To reduce mastectomy rates and/or omission of RT after breast
      conserving surgery, shorter, hypofractionated RT treatments have been introduced.
      More recently, the necessity of routinely treating the entire breast in all
      patients has been questioned, leading to the development of partial breast
      radiotherapy. With accelerated partial breast irradiation (APBI) these two
      approaches have been combined: the tumor bed with a 1-2 cm margin is irradiated
      either intra-operatively (single fraction) or postoperatively over 5-15 days.
      Different techniques have been developed, including interstitial brachytherapy,
      intra-cavity brachytherapy, intra-operative radiotherapy and external beam
      radiotherapy. These techniques are being evaluated in several ongoing phase III
      studies. Since its introduction, APBI has been the subject of continuous debate.
      ASTRO and GEC-ESTRO have published guidelines for patient selection for APBI, and
      strongly recommend that APBI be carried out within ongoing clinical trials.
      Recently, the patient selection criteria for APBI have also been up for debate,
      following the publication of results from different groups that do/do not confirm
      a difference in recurrence risk among the ASTRO defined risk groups. This paper
      reviews the different APBI techniques, current recommendations for patient
      selection, available clinical data and ongoing clinical trials. A case report is
      included to illustrate the need for careful follow-up of patients treated with
      APBI.

PMID- 23127280
TI  - Effects of peripheral benzodiazepine receptor ligand Ro5-4864 in four animal
      models of acute lung injury.
AB  - BACKGROUND: Acute lung injury (ALI) is a syndrome of inflammation and increased
      permeability of the blood-gas barrier. It is associated with high morbidity and
      mortality. Despite intensive research, treatments remain limited. The aim of the
      present study was to investigate the protective efficacy of a specific peripheral
      benzodiazepine receptor ligand, Ro5-4864, in experimental models of ALI in rats.
      METHODS: ALI was generated by four different methods: (1) intravenous (tail vein)
      injection of Escherichia coli (0111:B4) lipopolysaccaride (LPS), (2) cecal
      ligation and puncture (CLP), (3) mesenteric ischemia/reperfusion, and (4)
      intraperitoneal injection of alpha-naphthylthiourea (ANTU). Ro5-4864 was
      administered to rats intraperitoneally 30 min before ANTU and LPS administration
      or intravenously 15 min before reperfusion and CLP. The levels of pulmonary edema
      (lung weight/body weight ratio) and pleural effusion were measured, and the
      severity of ALI was scored (0-3). RESULTS: Ro5-4864 showed a dose-dependent and
      significant prophylactic effect on the ANTU-induced lung weight/body weight and
      pleural effusion/body weight ratios and histopathologic scores. Ro5-4864 also
      showed significant prophylactic effects against the LPS-induced lung weight/body
      weight ratio and histopathologic scores. Ro5-4864 significantly decreased the
      intra-alveolar edema and perialveolar hemorrhage scores in the CLP group.
      However, we found no prophylactic effect of Ro5-4864 on mesenteric
      ischemia/reperfusion-induced ALI at the dose used (2 mg/kg intraperitoneally).
      CONCLUSIONS: These results have demonstrated, for the first time, a protective
      effect of Ro5-4864 on experimental ALI induced by ANTU, LPS, and CLP. Ro5-4864
      might be a useful therapeutic agent for lung diseases, including ALI, in
      intensive care patients.

PMID- 23127281
TI  - Commentary on "Defining and predicting surgeon utilization at Forward Surgical
      Teams in Afghanistan".

PMID- 23127282
TI  - Intravital pathophysiological comparison of acid- and alkali-burn injuries in a
      murine model.
AB  - BACKGROUND: The breakdown of skin microcirculation plays a key role in the
      pathophysiology of chemical burns. Available data for alkali and acid injuries
      are rare. To determine the pathophysiological similarities and differences, two
      comparable in vivo acid and alkali burn models were developed. MATERIALS AND
      METHODS: Deep partial-thickness acid burns (32% hydrochloric acid) or alkali
      burns (11% sodium hydroxide solution) were inflicted to the ears of hairless mice
      (n = 17). Intravital fluorescent microscopy was used to assess microcirculation,
      angiogenesis, and leukocyte-endothelium interaction over a 21-d period. RESULTS:
      The angiogenesis occurred significantly faster after acid burns than after alkali
      burns in the first 3 days (nonperfused area day 3, 80% +/- 9% [acid] versus 94%
      +/- 17% [alkali]; P = 0.045) and then a significant acceleration occurs in the
      alkali group: nonperfused area day 14, 27% (alkali) versus 57% (acid), P = 0.004.
      The loss of functional vessel density was more pronounced after acid burns
      (directly after trauma, 87% [alkali] versus 79% [acid], P = 0.049). The other
      parameters such as rolling and sticking leukocytes, edema formation, and
      arteriolar and venular red blood cell velocities and diameters showed similar
      results. CONCLUSIONS: The comparison of analogous intravital acid and alkali
      burns shows that despite many similarities in the microcirculatory parameters,
      there was a marked difference particularly in the course of the tissue
      regeneration by angiogenesis. The longer lasting destruction by alkali burns
      stands in contrast to the later onset but faster regeneration by angiogenesis
      compared with that by acid burns.

PMID- 23127283
TI  - KmL3D: a non-parametric algorithm for clustering joint trajectories.
AB  - In cohort studies, variables are measured repeatedly and can be considered as
      trajectories. A classic way to work with trajectories is to cluster them in order
      to detect the existence of homogeneous patterns of evolution. Since cohort
      studies usually measure a large number of variables, it might be interesting to
      study the joint evolution of several variables (also called joint-variable
      trajectories). To date, the only way to cluster joint-trajectories is to cluster
      each trajectory independently, then to cross the partitions obtained. This
      approach is unsatisfactory because it does not take into account a possible co
      evolution of variable-trajectories. KmL3D is an R package that implements a
      version of k-means dedicated to clustering joint-trajectories. It provides
      facilities for the management of missing values, offers several quality criteria
      and its graphic interface helps the user to select the best partition. KmL3D can
      work with any number of joint-variable trajectories. In the restricted case of
      two joint trajectories, it proposes 3D tools to visualize the partitioning and
      then export 3D dynamic rotating-graphs to PDF format.

PMID- 23127284
TI  - Parallel evolutionary computation in bioinformatics applications.
AB  - A large number of optimization problems within the field of Bioinformatics
      require methods able to handle its inherent complexity (e.g. NP-hard problems)
      and also demand increased computational efforts. In this context, the use of
      parallel architectures is a necessity. In this work, we propose ParJECoLi, a Java
      based library that offers a large set of metaheuristic methods (such as
      Evolutionary Algorithms) and also addresses the issue of its efficient execution
      on a wide range of parallel architectures. The proposed approach focuses on the
      easiness of use, making the adaptation to distinct parallel environments
      (multicore, cluster, grid) transparent to the user. Indeed, this work shows how
      the development of the optimization library can proceed independently of its
      adaptation for several architectures, making use of Aspect-Oriented Programming.
      The pluggable nature of parallelism related modules allows the user to easily
      configure its environment, adding parallelism modules to the base source code
      when needed. The performance of the platform is validated with two case studies
      within biological model optimization.

PMID- 23127285
TI  - Allogenic mesenchymal stem cell transplantation ameliorates nephritis in lupus
      mice via inhibition of B-cell activation.
AB  - Recent evidence indicates that bone marrow-derived mesenchymal stem cells (BM
      MSCs) possess immunosuppressive properties both in vitro and in vivo. We have
      previously demonstrated that transplantation of human MSCs can significantly
      improve the autoimmune conditions in MRL/lpr mice. The current study aimed to
      determine the mechanisms by which murine BM-MSC transplantation (MSCT)
      ameliorates nephritis in MRL/lpr mice. In this study, we found that MSCT can
      significantly prolong the survival of MRL/lpr mice. Eight weeks after
      transplantation, MSCT-treated mice showed significantly smaller spleens than
      control animals, with fewer marginal zones (MZs), T1, T2, activated B-cells, and
      plasma cells. Moreover, serum levels of B-cell activating factor (BAFF) and IL-10
      in MSCT-treated mice decreased significantly compared to those in the control
      group, while levels of serum TGF-beta were increased. Notably, decreased BAFF
      expression in both spleen and kidney was accompanied by decreased production of
      anti-dsDNA autoantibodies and proteinuria in MSCT-treated mice. Since BAFF is
      mainly expressed by T-cells and dendritic cells, we incubated BM-MSCs and DCs
      together and found that the production of BAFF by DCs was suppressed by MSCs.
      Thus, our findings suggest that MSCT may suppress the excessive activation of B
      cells via inhibition of BAFF production in MRL/lpr mice. 

PMID- 23127286
TI  - MEK inhibition as a strategy for targeting residual breast cancer cells with low
      DUSP4 expression.
AB  - Lack of eradication of disseminated breast cancer by chemotherapy is a central
      clinical problem. Even tumors that show substantial shrinkage after drug
      treatment frequently relapse and eventually become refractory to all drugs
      available. The mechanisms underlying this lack of eradication are largely
      undefined and it is therefore difficult to develop curative strategies using
      systemic anti-cancer therapy. In a recent article low DUSP4 expression was
      reported to activate RAS-ERK signaling in residual breast cancer after
      neoadjuvant chemotherapy. This may be a druggable characteristic because MEK
      inhibition increases docetaxel sensitivity in a xenograft model. 

PMID- 23127287
TI  - Effect of water treatment on the growth potential of Vibrio cholerae and Vibrio
      parahaemolyticus in seawater.
AB  - In laboratory experiments we added Vibrio cholerae and Vibrio parahaemolyticus to
      bottles with seawater previously treated by filtration, UV, chlorine or ozone.
      The purpose was to investigate the influence of different treatment techniques on
      the growth potential of these bacteria in simulated ballast water tanks. Residual
      oxidants were removed before inoculation, and the bottles were incubated at 21 +/
      1  degrees C. The growth potential of the vibrios was investigated in two
      different experimental setups, i.e. in presence and absence of added natural
      microorganisms. In general, V. cholerae and V. parahaemolyticus rapidly lost
      their culturability after inoculation and storage in untreated seawater, but
      showed increased survival or growth in the treated water. Highest growth was
      observed in water previously exposed to high concentrations of ozone. Addition of
      natural microorganisms reduced the growth of V. cholerae and V. parahaemolyticus.

PMID- 23127288
TI  - Treatment of childhood and adolescent obesity: an integrative review of recent
      recommendations from five expert groups.
AB  - OBJECTIVE: To compare and contrast 5 sets of expert recommendations about the
      treatment of childhood and adolescent obesity. METHOD: We reviewed 5 sets of
      recent expert recommendations: 2007 health care organizations' four stage model,
      2007 Canadian clinical practice guidelines, 2008 Endocrine Society
      recommendations, 2009 seven step model, and 2010 U.S. Preventive Task Force
      recommendations. We described an empirically based sequential model by which
      expert recommendations may affect weight loss outcomes and then examined the
      recommendations pertaining to 4 treatments (self-help groups, outpatient
      cognitive behavior therapy [CBT], immersion CBT, and surgery). RESULTS: All of
      the expert committees supported using intensive dietary, physical activity, and
      cognitive-behavioral counseling; 2 of the 5 groups discouraged reliance on
      educational interventions alone; and 2 of the groups advised referring clients to
      increasingly intensive interventions, a stepped-care approach. CONCLUSIONS:
      Expert recommendations that include clear, simple, goal-oriented directions may
      impact the behaviors of health care providers most effectively and, in turn, help
      decrease childhood and adolescent obesity. Greatest benefits may accrue by
      encouraging health care providers and parents to view medical management and
      education as foundations to change but to pursue increasingly intensive viable
      options until overweight and obese children make clinically significant progress
      toward improved health and happiness.

PMID- 23127290
TI  - Does maintenance CBT contribute to long-term treatment response of panic disorder
      with or without agoraphobia? A randomized controlled clinical trial.
AB  - OBJECTIVE: We examined the possibility that maintenance cognitive behavior
      therapy (M-CBT) may improve the likelihood of sustained improvement and reduced
      relapse in a multi-site randomized controlled clinical trial of patients who met
      criteria for panic disorder with or without agoraphobia. METHOD: Participants
      were all patients (N = 379) who first began an open trial of acute-phase CBT.
      Patients completing and responding to acute-phase treatment were randomized to
      receive either 9 monthly sessions of M-CBT (n = 79) or assessment only (n = 78)
      and were then followed for an additional 12 months without treatment. RESULTS: M
      CBT produced significantly lower relapse rates (5.2%) and reduced work and social
      impairment compared to the assessment only condition (18.4%) at a 21-month follow
      up. Multivariate Cox proportional hazards models showed that residual symptoms of
      agoraphobia at the end of acute-phase treatment were independently predictive of
      time to relapse during 21-month follow-up (hazards ratio = 1.15, p < .01).
      CONCLUSIONS: M-CBT aimed at reinforcing acute treatment gains to prevent relapse
      and offset disorder recurrence may improve long-term outcome for panic disorder
      with and without agoraphobia.

PMID- 23127291
TI  - Comparison of intranasal azelastine to intranasal fluticasone propionate for
      symptom control in moderate-to-severe seasonal allergic rhinitis.
AB  - Intranasal corticosteroids are considered the most effective therapy for moderate
      to-severe seasonal allergic rhinitis (SAR) and recommended first line in
      guidelines. It is uncertain whether intranasal antihistamines have comparable
      efficacy. This study was designed to compare the efficacy  of azelastine (AZE;
      137 MUg/spray) and fluticasone propionate (FP; 50 MUg/spray), both given as 1
      spray/nostril bid (i.e., approved dosing regimen in the United States), in SAR
      via a post hoc analysis of data from a previously published direct-comparison
      study. Six  hundred ten moderate-to-severe SAR patients (>=12 years old) were
      randomized into a double-blind, placebo-controlled, parallel-group trial. The
      primary efficacy variable was change from baseline in reflective total nasal
      symptom score (rTNSS (morning and evening), over 14 days. Reflective  total
      ocular symptom score (rTOSS) was a key secondary variable. Reflective total of
      seven symptom scores (rT7SS [nasal plus ocular symptoms]) and time to >=50%
      reduction from baseline in these key parameters were also analyzed. AZE and FP
      reduced rTNSS from baseline by a similar degree  (-3.25 versus -3.84; p =
      0.2014). Patients experienced comparable improvement in rTOSS (-2.62 versus 
      2.17; p = 0.2371) and rT7SS (-5.83 versus -6.05; p = 0.7820). FP was superior to
      AZE in alleviating rhinorrhea (-1.15 versus -0.87; p = 0.0433),  but AZE showed
      comparable efficacy for all other nasal and ocular symptoms. There was no
      clinically or statistically significant difference between AZE (-1.17) and FP (
      1.43) for reduction in the overall rhinitis quality of life questionnaire score
      (although FP, but not AZE, significantly  differed from placebo). A similar
      proportion of patients in the AZE and FP groups achieved a 50% reduction in
      rTNSS. However, more AZE patients (53.0%) exhibited a 50% reduction in rTOSS by
      day 14 versus FP (39.6%), and <=3 days faster (p = 0.028). Intranasal AZE (137
      micrograms/spray) and  intranasal FP (50 micrograms/spray), both 1 spray/nostril
      b.i.d., had comparable efficacy in symptom control in moderate-to-severe SAR.

PMID- 23127292
TI  - Prognostic interaction between expression of p53 and estrogen receptor in
      patients with node-negative breast cancer: results from IBCSG Trials VIII and IX.
AB  - INTRODUCTION: The prognostic significance of p53 protein expression in early
      breast cancer remains uncertain, with some but not all studies finding an
      association with poorer outcomes. Estrogen receptor (ER) expression is both a
      positive prognostic marker and predictive of response to endocrine therapies. The
      relationship between these biomarkers is unknown. METHODS: We constructed tissue
      microarrays (TMAs) from available pathological material from 1113 patients
      participating in two randomized clinical trials comparing endocrine therapy alone
      versus chemo-endocrine therapy in node-negative breast cancer. Expression of p53
      defined as >10% positive nuclei was analyzed together with prior
      immunohistochemical assays of ER performed at central pathological review of
      whole tumor sections. RESULTS: ER was present (i.e. >1% positive tumor cell
      nuclei) in 80.1% (880/1092). p53 expression was significantly more frequent when
      ER was absent, 125/212 (59%) than when ER was present, 171/880 (19%), p <0.0001.
      A significant qualitative interaction was observed such that p53 expression was
      associated with better disease-free survival (DFS) and overall survival (OS)
      among patients whose tumors did not express ER, but worse DFS and OS among
      patients whose tumors expressed ER. The interaction remained significant after
      allowance for pathologic variables, and treatment. Similar effects were seen when
      luminal and non-luminal intrinsic subtypes were compared. CONCLUSIONS:
      Interpretation of the prognostic significance of p53 expression requires
      knowledge of concurrent expression of ER. The reason for the interaction between
      p53 and ER is unknown but may reflect qualitatively different p53 mutations
      underlying the p53 expression in tumors with or without ER expression. TRIAL
      REGISTRATION: Current Controlled Trials ACTRN12607000037404 (Trial VIII) and
      ACTRN12607000029493 (Trial IX).

PMID- 23127293
TI  - Abuse rates and routes of administration of reformulated extended-release
      oxycodone: initial findings from a sentinel surveillance sample of individuals
      assessed for substance abuse treatment.
AB  - Oxycodone hydrochloride controlled-release, also known as extended-release
      oxycodone (ER oxycodone), was reformulated with physicochemical barriers to
      crushing and dissolving intended to reduce abuse through nonoral routes of
      administration (ROAs) that require tampering (eg, injecting and snorting).
      Manufacturer shipments of original ER oxycodone (OC) stopped on August 5, 2010,
      and reformulated ER oxycodone (ORF) shipments started August 9, 2010. A sentinel
      surveillance sample of 140,496 individuals assessed for substance abuse treatment
      at 357 U.S. centers between June 1, 2009, and March 31, 2012, was examined for
      prevalence and prescription-adjusted prevalence rates of past-30-day abuse via
      any route, as well as abuse through oral, nonoral, and specific ROAs for ER
      oxycodone and comparators (ER morphine and ER oxymorphone) before and after ORF
      introduction. Significant reductions occurred for 8 outcome measures of ORF
      versus OC historically. Abuse of ORF was 41% lower (95% CI: -44 to -37) than
      historical abuse for OC, with oral abuse 17% lower (95% CI: -23 to -10) and
      nonoral abuse 66% lower (95% CI: -69 to -63). Significant reductions were not
      observed for comparators. Observations were consistent with the goals of a tamper
      resistant formulation for an opioid. Further research is needed to determine the
      persistence and generalizability of these findings. PERSPECTIVE: This article
      presents preliminary findings indicating that 8 outcome measures of abuse of a
      reformulated ER oxycodone were lower than that for original ER oxycodone
      historically, particularly through nonoral ROAs that require tampering (ie,
      injection, snorting, smoking), in a sentinel sample of individuals assessed for
      substance use problems for treatment planning.

PMID- 23127294
TI  - We discount the pain of others when pain has no medical explanation.
AB  - The present studies investigated the impact of medical and psychosocial
      information on the observer's estimations of pain, emotional responses, and
      behavioral tendencies toward another person in pain. Participants were recruited
      from the community (study 1: N = 39 women, 10 men; study 2: N = 41 women, 12 men)
      and viewed videos of 4 patients expressing pain, paired with vignettes describing
      absence or presence of 1) medical evidence for the pain and 2) psychosocial
      influences on the pain experience. A similar methodology was used for studies 1
      and 2, except for the explicit manipulation of the presence/absence of
      psychosocial influences in study 2. For each patient video, participant
      estimations of each patient's pain and their own distress, sympathy, and
      inclination to help were assessed. In both studies, results indicated lower
      ratings on all measures when medical evidence for pain was absent. Overall, no
      effect of psychosocial influences was found, except in study 2 where participants
      indicated feeling less distress when psychosocial influences were present. The
      findings suggest that pain is taken less seriously when there is no medical
      evidence for the pain. The findings are discussed in terms of potential
      mechanisms underlying pain estimations as well as implications for caregiving
      behavior. PERSPECTIVE: The present studies indicate that observers take the pain
      of others less seriously in the absence of clear medical evidence for the pain.
      These findings are important to further understand the social context in which
      pain for which there is no clear medical explanation is experienced.

PMID- 23127295
TI  - A novel vibratory stimulation-based splint for chronic and untreatable
      masticatory myofascial pain: a case-series.
AB  - AIM: This clinical report aimed to introduce a novel vibratory stimulation-based
      occlusal splint (VibS) for management of chronic and untreatable masticatory
      myofascial pain (MMFP). METHODS: This study was conducted on four chronic MMFP
      patients (mean age: 27.5+/-5.56 years, females) who were diagnosed according to
      the research diagnostic criteria for temporomandibular disorders (RDC/TMD), and
      who were using stabilization splints for more than 6 months and still complained
      of pain above 40 mm in a 100-mm VAS scale. The included subjects utilized the
      active VibS and subsequently the inactive VibS during 30 days in each trial,
      separated by a wash-out period of at least 8 months. VAS pain levels were the
      only measured dependent variable, and were recorded before and after the use of
      active VibS and inactive VibS. RESULTS: At baseline, mean VAS pain levels before
      using the active or inactive splint were 54.5+/-19.8 mm and 44.0+/-13.6 mm,
      respectively. After using the active VibS, mean pain level decreased by 77%
      (VASpos-pre=-42.0+/-30.3 mm). On the other hand, after using the inactive VibS,
      severe pain aggravation of 67% in magnitude was observed (VASpos-pre=+29.5+/-21.5
      mm). CONCLUSION: This case-series study demonstrated a good tendency of this
      novel VibS in chronic MMFP alleviation after a 4-week management period compared
      to a control inactive VibS.

PMID- 23127297
TI  - Viability of Ascaris suum eggs in stored raw and separated liquid slurry.
AB  - Separation of pig slurry into solid and liquid fractions is gaining importance as
      a way to manage increasing volumes of slurry. In contrast to solid manure and
      slurry, little is known about pathogen survival in separated liquid slurry. The
      viability of Ascaris suum eggs, a conservative indicator of fecal pollution, and
      its association with ammonia was investigated in separated liquid slurry in
      comparison with raw slurry. For this purpose nylon bags with 6000 eggs each were
      placed in 1 litre bottles containing one of the two fractions for 308 days at 5 
      degrees C or 25  degrees C. Initial analysis of helminth eggs in the separated
      liquid slurry revealed 47 Ascaris eggs per gramme. At 25  degrees C, egg
      viability declined to zero with a similar trend in both raw slurry and the
      separated liquid slurry by day 308, a time when at 5  degrees C 88% and 42% of
      the eggs were still viable in separated liquid slurry and raw slurry,
      respectively. The poorer survival at 25  degrees C was correlated with high
      ammonia contents in the range of 7.9-22.4 mM in raw slurry and 7.3-23.2 mM in
      liquid slurry compared to 3.2-9.5 mM in raw slurry and 2.6-9.5 mM in liquid
      slurry stored at 5  degrees C. The study demonstrates that at 5  degrees C, A.
      suum eggs have a higher viability in separated liquid slurry as compared to raw
      slurry. The hygiene aspect of this needs to be further investigated when
      separated liquid slurry is used to fertilize pastures or crops.

PMID- 23127298
TI  - Dax gets the nod: toddlers detect and use social cues to evaluate testimony.
AB  - Children ages 18 and 24 months were assessed for the ability to understand and
      learn from an adult's nonverbal expression of agreement and disagreement with a
      speaker's claims. In one type of communicative exchange, a speaker made 2
      different claims about the identity or location of an object. The hearer nodded
      her head in agreement with one claim and shook her head in disagreement with the
      other claim. In a second type of exchange, the speaker asked 2 different
      questions about the identity or location of an object. The hearer nodded her head
      in response to one question and shook her head in response to the other. The 24
      month-olds grasped the implication of these gestural responses, by inferring the
      correct name or location of the object. The 18-month-olds showed a limited grasp
      of their implications. Thus, in learning from others' testimony, toddlers focus
      not only on the claims of a single speaker but also on whether that information
      is accepted or rejected by another hearer. In particular, they detect and act on
      social cues of assent and dissent.

PMID- 23127296
TI  - Exaggerated neurobiological sensitivity to threat as a mechanism linking anxiety
      with increased risk for diseases of aging.
AB  - Anxiety disorders increase risk for the early development of several diseases of
      aging. Elevated inflammation, a common risk factor across diseases of aging, may
      play a key role in the relationship between anxiety and physical disease.
      However, the neurobiological mechanisms linking anxiety with elevated
      inflammation remain unclear. In this review, we present a neurobiological model
      of the mechanisms by which anxiety promotes inflammation. Specifically we propose
      that exaggerated neurobiological sensitivity to threat in anxious individuals may
      lead to sustained threat perception, which is accompanied by prolonged activation
      of threat-related neural circuitry and threat-responsive biological systems
      including the hypothalamic-pituitary-adrenal (HPA) axis, autonomic nervous system
      (ANS), and inflammatory response. Over time, this pattern of responding can
      promote chronic inflammation through structural and functional brain changes,
      altered sensitivity of immune cell receptors, dysregulation of the HPA axis and
      ANS, and accelerated cellular aging. Chronic inflammation, in turn, increases
      risk for diseases of aging. Exaggerated neurobiological sensitivity to threat may
      thus be a treatment target for reducing disease risk in anxious individuals.

PMID- 23127299
TI  - Timing of high-quality child care and cognitive, language, and preacademic
      development.
AB  - The effects of high- versus low-quality child care during 2 developmental periods
      (infant-toddlerhood and preschool) were examined using data from the National
      Institute of Child Health and Human Development Study of Early Child Care.
      Propensity score matching was used to account for differences in families who
      used different combinations of child care quality during the 2 developmental
      periods. Findings indicated that cognitive, language, and preacademic skills
      prior to school entry were highest among children who experienced high-quality
      care in both the infant-toddler and preschool periods, somewhat lower among
      children who experienced high-quality child care during only 1 of these periods,
      and lowest among children who experienced low-quality care during both periods.
      Irrespective of the care received during infancy-toddlerhood, high-quality
      preschool care was related to better language and preacademic outcomes at the end
      of the preschool period; high-quality infant-toddler care, irrespective of
      preschool care, was related to better memory skills at the end of the preschool
      period.

PMID- 23127300
TI  - Attachment theory and theory of planned behavior: an integrative model predicting
      underage drinking.
AB  - Research indicates that peer and maternal bonds play important but sometimes
      contrasting roles in the outcomes of children. Less is known about attachment
      bonds to these 2 reference groups in young adults. Using a sample of 351
      participants (18 to 20 years of age), the research integrated two theoretical
      traditions: attachment theory and theory of planned behavior (TPB). The
      predictive contribution of both theories was examined in the context of underage
      adult alcohol use. Using full structural equation modeling, results substantiated
      the hypotheses that secure peer attachment positively predicted norms and
      behavioral control toward alcohol, but secure maternal attachment inversely
      predicted attitudes and behavioral control toward alcohol. Alcohol attitudes,
      norms, and behavioral control each uniquely explained alcohol intentions, which
      anticipated an increase in alcohol behavior 1 month later. The hypothesized
      processes were statistically corroborated by tests of indirect and total effects.
      These findings support recommendations for programs designed to curtail risky
      levels of underage drinking using the tenets of attachment theory and TPB.

PMID- 23127301
TI  - Phase-adequate engagement at the post-school transition.
AB  - The transition from general education (e.g., high school) to vocational and
      tertiary education (e.g., college, vocational school) or to the labor market
      presents a number of developmental challenges. These challenges include making
      career choices and, more broadly, managing the transition. Coping with these
      challenges depends on the individual, their social network, and wider societal,
      cultural, and institutional conditions. This article discusses the informative
      value of developmental regulation, career development, and identity theories, for
      conceptualizing phase-adequate engagement at the post-school transition. Although
      previous psychological research has focused on individuals' career and transition
      related engagement and its outcomes, we suggest this picture is limited because
      little is known about how young people's engagement is complemented and affected
      by the behavior of significant others and shaped by structural constraints and
      opportunities. Implications for future developmental research are discussed.
      (PsycINFO Database Record (c) 2012 APA, all rights reserved).

PMID- 23127302
TI  - Task value profiles across subjects and aspirations to physical and IT-related
      sciences in the United States and Finland.
AB  - Two independent studies were conducted to extend previous research by examining
      the associations between task value priority patterns across school subjects and
      aspirations toward the physical and information technology- (IT-) related
      sciences. Study 1 measured task values of a sample of 10th graders in the United
      States (N = 249) across (a) physics and chemistry, (b) math, and (c) English.
      Study 2 measured task values of a sample of students in the second year of high
      school in Finland (N = 351) across (a) math and science, (b) Finnish, and (c) the
      arts and physical education. In both studies, students were classified into
      groups according to how they ranked math and science in relation to the other
      subjects. Regression analyses indicated that task value group membership
      significantly predicted subsequent aspirations toward physical and IT-related
      sciences measured 1-2 years later. The task value groups who placed the highest
      priority on math and science were significantly more likely to aspire to physical
      and IT-related sciences than were the other groups. These findings provide
      support for the theoretical assumption regarding the predictive role of
      intraindividual hierarchical patterns of task values for subsequent preferences
      and choices suggested by the Eccles [Parsons] (1983) expectancy-value model.

PMID- 23127303
TI  - Can we scientifically and reliably measure the level of consciousness in
      vegetative and minimally conscious States? Rasch analysis of the coma recovery
      scale-revised.
AB  - OBJECTIVES: (1) To appraise, by the means of Rasch analysis, the internal
      validity and reliability of the Coma Recovery Scale-Revised (CRS-R) in a sample
      of patients with disorder of consciousness (DOC); and (2) to provide information
      about the comparability of CRS-R scores across persons with DOC across different
      settings and groups, including different etiologies. DESIGN: Multicenter
      observational prospective study. SETTING: Two rehabilitation wards, 1
      intermediate care facility, and 2 nursing homes in Italy. PARTICIPANTS:
      Consecutively admitted patients (N=129) for which assessments at 2 different time
      points were available, giving a total sample of 258 observations. INTERVENTIONS:
      Not applicable. MAIN OUTCOME MEASURE: CRS-R. RESULTS: After controlling for any
      possible dependency between persons' measures collected at different time points,
      and for uniform differential item functioning by etiology showed by the visual
      subscale, Rasch analysis demonstrated adequate satisfaction of all the model's
      requirements, including adequate ordering of scoring categories,
      unidimensionality, local independence, invariance (chi(2)21=27.798, P=.146), and
      absence of differential item functioning across patients' sex, age, time, and
      setting. The reliability (person separation index=.896) was adequate for
      individual person measurement. We devised a practical raw score to measure
      conversion tables based on the CRS-R calibrations. CONCLUSIONS: The CRS-R is a
      psychometrically sound and robust measurement tool. The linear measures of
      ability derived from the CRS-R total scores do satisfy all the principles of
      scientific measurement and are sufficiently reliable for high stakes assessments,
      such as the diagnosis of the level of consciousness in individual patients.
      Future studies are needed to directly explore the capabilities of the CRS-R
      measures to reduce the risk of vegetative state misdiagnosis.

PMID- 23127304
TI  - Prevalence of myofascial trigger points in the hip in patellofemoral pain.
AB  - OBJECTIVES: To determine the prevalence of myofascial trigger points (MTrPs) in
      the gluteus medius (GMe) and quadratus lumborum (QL) for subjects with
      patellofemoral pain (PFP), and to examine the relationship between MTrPs and
      force production of the GMe after treatment. DESIGN: Randomized controlled trial.
      SETTING: A physical therapy clinic. PARTICIPANTS: Subjects (N=52; mean age +/-
      SD, 30+/-12y; mean height +/- SD, 172+/-10cm; mean mass +/- SD, 69+/-14kg)
      volunteered and were divided into 2 groups: a PFP group (n=26) consisting of
      subjects with PFP, and a control group (n=26) with no history of PFP.
      INTERVENTIONS: Patients with PFP received trigger point pressure release therapy
      (TPPRT). MAIN OUTCOME MEASURES: Hip abduction isometric strength and the presence
      of MTrPs. RESULTS: Prevalence of bilateral GMe and QL MTrPs for the PFP group was
      significantly higher compared with controls (P=.001). Subjects in the PFP group
      displayed significantly less hip abduction strength compared with the control
      group (P=.007). However, TPPRT did not result in increased force production.
      CONCLUSIONS: Subjects with PFP have a higher prevalence of MTrPs in bilateral GMe
      and QL muscles. They demonstrate less hip abduction strength compared with
      controls, but the TPPRT did not result in an increase in hip abduction strength.

PMID- 23127305
TI  - Active mobilization for mechanically ventilated patients: a systematic review.
AB  - OBJECTIVE: To investigate the effectiveness and safety of active mobilization on
      improving physical function and hospital outcomes in patients undergoing
      mechanical ventilation for more than 24 hours. DATA SOURCES: PubMed, Embase,
      CINAHL, CENTRAL, Physiotherapy Evidence Database, SinoMed, and ISI Web of
      Knowledge were searched for randomized controlled trials (RCTs), quasi-RCTs,
      other comparative studies, and case series with 10 or more consecutive cases.
      Additional studies were identified through references, citation tracking, and by
      contacting the authors of eligible studies. STUDY SELECTION: Two reviewers
      independently selected potential studies according to the inclusion criteria.
      DATA EXTRACTION: Two reviewers independently extracted data and assessed the
      methodologic quality. DATA SYNTHESIS: A narrative form was used to summarize
      study characteristics and outcomes, because the substantial heterogeneity between
      the individual studies precluded formal meta-analyses. Among the 17 eligible
      studies, 7 RCTs, 1 quasi-RCT, 1 prospective cohort study, and 1 history
      controlled study were used to examine the effectiveness; and 2 RCTs, 1
      prospective cohort study, and 7 case series were used to examine the safety of
      active mobilization in patients receiving mechanical ventilation for more than 24
      hours. We found that active mobilization may improve muscle strength, functional
      independence, and the ability to wean from ventilation and may decrease the
      length of stay in the intensive care unit (ICU) and hospital. However, only 1
      study reported that active mobilization reduced the 1-year mortality rate. No
      serious adverse events were reported among included studies. CONCLUSIONS: Active
      mobilization appears to have a positive effect on physical function and hospital
      outcomes in mechanical ventilation patients. Early active mobilization protocols
      may be initiated safely in the ICU setting and continued in post-ICU settings.
      However, the current available studies have great heterogeneity and limited
      methodologic quality. Further research is needed to provide more robust evidence
      to support the effectiveness and safety of active mobilization.

PMID- 23127306
TI  - Randomized clinical trial of oral health promotion interventions among patients
      following stroke.
AB  - OBJECTIVE: To evaluate the effectiveness of oral health promotion interventions
      on clinical oral health. DESIGN: Single-blind randomized controlled trial
      conducted over 3 weeks of in-hospital rehabilitation. SETTING: Stroke
      rehabilitation ward in Hong Kong. PARTICIPANTS: Patients with stroke (N=102)
      admitted to the rehabilitation ward. INTERVENTIONS: Patients were randomly
      assigned either: (1) oral hygiene instruction, (2) oral hygiene instruction and
      chlorhexidine mouthrinse, or (3) oral hygiene instruction, chlorhexidine
      mouthrinse, and assisted brushing. MAIN OUTCOME MEASURES: Dental plaque, gingival
      bleeding, and oral functional status were assessed at baseline and review.
      Development of infectious complications were also monitored during the clinical
      trial. RESULTS: Poor oral hygiene and an overall neglect of oral hygiene
      practices were observed at baseline. Reductions in dental plaque were
      significantly greater in the 2 groups receiving chlorhexidine compared with the
      group receiving oral hygiene instruction alone (P<.001). Reductions in gingival
      bleeding scores were 3- to 4-fold greater in groups receiving chlorhexidine. No
      cases of pneumonia were observed during the course of the clinical trial.
      CONCLUSIONS: The oral health condition of patients may be safeguarded after acute
      stroke with the use of chlorhexidine mouthrinse in conjunction with a standard
      mechanical plaque removal tool, such as an electric toothbrush. These
      interventions are acceptable to the majority of patients, and their
      administration poses a minimal burden to rehabilitation ward staff.

PMID- 23127307
TI  - Cueing and gait improvement among people with Parkinson's disease: a meta
      analysis.
AB  - OBJECTIVE: To compare the relative efficacy of visual versus auditory cueing on
      gait among individuals with Parkinson's disease (PD). DATA SOURCES: A systematic
      search was completed up to September 2011, using the following databases: EMBASE,
      Scopus, Medline, CINAHL, and PubMed. STUDY SELECTION: Four authors searched the
      databases using the following terms: Parkinson's disease (including
      abbreviations), gait, cadence, step, pace, cueing, cues, and prompt. All studies
      that evaluated the effect of cueing on gait in PD were selected by consensus of 2
      pairs of authors who reviewed the titles and abstracts. Each pair of authors then
      applied the inclusion and exclusion criteria to each study, and 25 articles were
      chosen. Inclusion criteria were cueing studies that reported pre- and postoutcome
      measures of gait parameters. Exclusion criteria were lack of data and studies
      that evaluated gait aids. DATA EXTRACTION: Gait measures of cadence, stride
      length, and velocity, before and after cueing, were collected from each study. If
      data were represented in graphs, a pair of authors extracted the data points
      individually, then compared and averaged values. DATA SYNTHESIS: The data were
      synthesized using a meta-analysis based on cue type. Auditory cueing demonstrated
      significant improvement of cadence (Hedge g=.556; 95% confidence interval [CI],
      .291-.893), stride length (Hedge g=.497; 95% CI, .289-.696), and velocity (Hedge
      g=.544; 95% CI, .294-.795). In contrast, visual cueing significantly improved
      stride length only (Hedge g=.554; 95% CI, .072-1.036). CONCLUSIONS: The findings
      suggest that auditory cueing is more effective for treating gait disorders in PD.
      Further research is needed to determine the optimum auditory cueing strategy for
      gait improvements.

PMID- 23127308
TI  - Falls in people with multiple sclerosis who use a walking aid: prevalence,
      factors, and effect of strength and balance interventions.
AB  - OBJECTIVES: To investigate falls prevalence, factors associated with falling, and
      the effects of balance and strengthening interventions on falls in persons with
      multiple sclerosis (MS). DESIGN: Baseline and posttreatment data from a
      randomized controlled trial. SETTING: Community. PARTICIPANTS: People with MS
      (N=111) who use bilateral support for gait. INTERVENTIONS: Group and one-on-one
      physiotherapy. MAIN OUTCOME MEASURES: Falls prevalence was assessed using
      retrospective recall. Demographic information was collected, impairments of body
      function were assessed, and results from the Berg Balance Scale, 6-minute walk
      test (6MWT), Multiple Sclerosis Impact Scale-29 version 2 physical and
      psychological scores, and the Modified Fatigue Impact Scale (MFIS) were obtained.
      RESULTS: The prevalence of falls in a 3-month period was 50.5% among participants
      with MS, of whom 28% had more than 1 fall. Fallers had a greater physical (mean
      difference, -3.9; P=.048) and psychological (median difference, -4.5; P=.001)
      impact of MS and a greater impact of fatigue (mean difference, -9.4; P=.002). A
      logistic regression analysis found that the MFIS score made a unique, significant
      contribution to the model (odds ratio=1.04; 95% confidence interval, 1.018
      1.079), correctly identifying 68% of fallers. A 10-week group physiotherapy
      intervention significantly reduced both the number of fallers (58.3% before to
      22.9% after intervention, P=.005) and the number of falls (63 before to 25 after
      intervention, P=.001). CONCLUSIONS: The prevalence of falls is high in this
      population of persons with MS, and the impact of MS and of fatigue is greater in
      fallers. Development and evaluation of interventions to reduce falls risk and the
      transition to faller or multiple faller status are required.

PMID- 23127309
TI  - Breast cancer risk assessment across the risk continuum: genetic and nongenetic
      risk factors contributing to differential model performance.
AB  - INTRODUCTION: Clinicians use different breast cancer risk models for patients
      considered at average and above-average risk, based largely on their family
      histories and genetic factors. We used longitudinal cohort data from women whose
      breast cancer risks span the full spectrum to determine the genetic and
      nongenetic covariates that differentiate the performance of two commonly used
      models that include nongenetic factors - BCRAT, also called Gail model, generally
      used for patients with average risk and IBIS, also called Tyrer Cuzick model,
      generally used for patients with above-average risk. METHODS: We evaluated the
      performance of the BCRAT and IBIS models as currently applied in clinical
      settings for 10-year absolute risk of breast cancer, using prospective data from
      1,857 women over a mean follow-up length of 8.1 years, of whom 83 developed
      cancer. This cohort spans the continuum of breast cancer risk, with some subjects
      at lower than average population risk. Therefore, the wide variation in
      individual risk makes it an interesting population to examine model performance
      across subgroups of women. For model calibration, we divided the cohort into
      quartiles of model-assigned risk and compared differences between assigned and
      observed risks using the Hosmer-Lemeshow (HL) chi-squared statistic. For model
      discrimination, we computed the area under the receiver operator curve (AUC) and
      the case risk percentiles (CRPs). RESULTS: The 10-year risks assigned by BCRAT
      and IBIS differed (range of difference 0.001 to 79.5). The mean BCRAT- and IBIS
      assigned risks of 3.18% and 5.49%, respectively, were lower than the cohort's 10
      year cumulative probability of developing breast cancer (6.25%; 95% confidence
      interval (CI) = 5.0 to 7.8%). Agreement between assigned and observed risks was
      better for IBIS (HL X4(2) = 7.2, P value 0.13) than BCRAT (HL X4(2) = 22.0, P
      value <0.001). The IBIS model also showed better discrimination (AUC = 69.5%, CI
      = 63.8% to 75.2%) than did the BCRAT model (AUC = 63.2%, CI = 57.6% to 68.9%). In
      almost all covariate-specific subgroups, BCRAT mean risks were significantly
      lower than the observed risks, while IBIS risks showed generally good agreement
      with observed risks, even in the subgroups of women considered at average risk
      (for example, no family history of breast cancer, BRCA1/2 mutation negative).
      CONCLUSIONS: Models developed using extended family history and genetic data,
      such as the IBIS model, also perform well in women considered at average risk
      (for example, no family history of breast cancer, BRCA1/2 mutation negative).
      Extending such models to include additional nongenetic information may improve
      performance in women across the breast cancer risk continuum.

PMID- 23127310
TI  - A preexistent hypoxic gene signature predicts impaired islet graft function and
      glucose homeostasis.
AB  - We examined whether hypoxic exposure prior to the event of transplantation would
      have a positive or negative effect upon later islet graft function. Mouse islets
      exposed to hypoxic culture were transplanted into syngeneic recipients. Islet
      graft function, beta-cell physiology, as well as molecular changes were examined.
      Expression of hypoxia-response genes in human islets pre- and posttransplant was
      examined by microarray. Hypoxia-preexposed murine islet grafts provided poor
      glycemic control in their syngeneic recipients, marked by persistent
      hyperglycemia and pronounced glucose intolerance with failed first- and second
      phase glucose-stimulated insulin secretion in vivo. Mechanistically, hypoxic
      preexposure stabilized HIF-1alpha with a concomitant increase in hypoxic-response
      genes including LDHA, and a molecular gene set, which would favor glycolysis and
      lactate production and impair glucose sensing. Indeed, static incubation studies
      showed that hypoxia-exposed islets exhibited dysregulated glucose responsiveness
      with elevated basal insulin secretion. Isolated human islets, prior to
      transplantation, express a characteristic hypoxia-response gene expression
      signature, including high levels of LDHA, which is maintained posttransplant.
      Hypoxic preexposure of an islet graft drives a HIF-dependent switch to glycolysis
      with subsequent poor glycemic control and loss of GSIS. Early intervention to
      reverse or prevent these hypoxia-induced metabolic gene changes may improve
      clinical islet transplantation. 

PMID- 23127311
TI  - Some "face time" for health information technology.

PMID- 23127312
TI  - Copying and pasting patient treatment notes.

PMID- 23127313
TI  - Use of electronic patient data in research.

PMID- 23127314
TI  - Limits to patient selection.

PMID- 23127315
TI  - Medical education and decision-support systems.

PMID- 23127317
TI  - Reassessing "minor" breaches of confidentiality.

PMID- 23127318
TI  - Use of bar-code technology to reduce drug administration errors.

PMID- 23127319
TI  - Vancomycin in the treatment of pediatric staphylococcal infections.

PMID- 23127320
TI  - Health Law the hitech act-an overview.

PMID- 23127321
TI  - Ethical dimensions of meaningful use requirements for electronic health records.

PMID- 23127322
TI  - Does health information technology dehumanize health care?

PMID- 23127323
TI  - Development of the electronic health record.

PMID- 23127324
TI  - The promise of health information technology.

PMID- 23127325
TI  - Mindful use of health information technology.

PMID- 23127327
TI  - Outcome of ICU patients with Clostridium difficile infection.
AB  - INTRODUCTION: As data from Clostridium difficile infection (CDI) in intensive
      care unit (ICU) are still scarce, our objectives were to assess the morbidity and
      mortality of ICU-acquired CDI. METHODS: We compared patients with ICU-acquired
      CDI (watery or unformed stools occurring >= 72 hours after ICU admission with a
      stool sample positive for C. difficile toxin A or B) with two groups of controls
      hospitalized at the same time in the same unit. The first control group comprised
      patients with ICU-acquired diarrhea occurring >= 72 hours after ICU admission
      with a stool sample negative for C. difficile and for toxin A or B. The second
      group comprised patients without any diarrhea. RESULTS: Among 5,260 patients, 512
      patients developed one episode of diarrhea. Among them, 69 (13.5%) had a CDI; 10
      (14.5%) of them were community-acquired, contrasting with 12 (17.4%) that were
      hospital-acquired and 47 (68%) that were ICU-acquired. A pseudomembranous colitis
      was associated in 24/47 (51%) ICU patients. The median delay between diagnosis
      and metronidazole administration was one day (25th Quartile; 75th Quartile (0; 2)
      days). The case-fatality rate for patients with ICU-acquired CDI was 10/47
      (21.5%), as compared to 112/443 (25.3%) for patients with negative tests. Neither
      the crude mortality (cause specific hazard ratio; CSHR = 0.70, 95% confidence
      interval; CI 0.36 to 1.35, P = 0.3) nor the adjusted mortality to confounding
      variables (CSHR = 0.81, 95% CI 0.4 to 1.64, P = 0.6) were significantly different
      between CDI patients and diarrheic patients without CDI. Compared to the general
      ICU population, neither the crude mortality (SHR = 0.64, 95% CI 0.34 to 1.21, P =
      0.17), nor the mortality adjusted to confounding variables (CSHR = 0.71, 95%
      confidence interval (CI) 0.38 to 1.35, P = 0.3), were significantly different
      between the two groups. The estimated increase in the duration of stay due to CDI
      was 8.0 days +/- 9.3 days, (P = 0.4) in comparison to the diarrheic population,
      and 6.3 days +/- 4.3 (P = 0.14) in comparison to the general ICU population.
      CONCLUSIONS: If treated early, ICU-acquired CDI is not independently associated
      with an increased mortality and impacts marginally the ICU length of stay.

PMID- 23127328
TI  - Temporal variation of Mexiconema cichlasomae (Nematoda: Daniconematidae) in the
      Mayan cichlid fish Cichlasoma urophthalmus and its intermediate host Argulus
      yucatanus from a tropical coastal lagoon.
AB  - The aim of the present investigation was to determine whether temporal variation
      in environmental factors such as rainfall or temperature influence long-term
      fluctuations in the prevalence and mean abundance of the nematode Mexiconema
      cichlasomae in the cichlid fish Cichlasoma uropthalmus and its crustacean
      intermediate host, Argulus yucatanus. The study was undertaken in a tropical
      coastal lagoon in the Yucatan Peninsula (south-eastern Mexico) over an 8-year
      period. Variations in temperature, rainfall and monthly infection levels for both
      hosts were analysed using time series and cross-correlations to detect possible
      recurrent patterns. Infections of M. cichlasomae in A. yucatanus showed annual
      peaks, while in C. urophthalmus peaks were bi-annual. The latter appear to be
      related to the accumulation of several generations of this nematode in C.
      urophthalmus. Rainfall and temperature appear to be key environmental factors in
      influencing temporal variation in the infection of M. cichlasomae over periods
      longer than a year together with the accumulation of larval stages throughout
      time.

PMID- 23127329
TI  - Improved method of producing human neural progenitor cells of high purity and in
      large quantities from pluripotent stem cells for transplantation studies.
AB  - Transplantation of human neural progenitor cells (hNPCs) is a promising
      therapeutic approach for various diseases of the central nervous system (CNS).
      Reliable testing of hNPC transplantation in animal models of neurological
      diseases requires that these cells can be produced in sufficient amounts, show
      consistent homogeneity as a neural cell population, and be reliably labeled for
      in vivo tracking. In addition, the cells should be characterized as being at the
      optimal state of differentiation favoring successful engraftment. Here, we show
      that high numbers of purified hNPCs can be produced from human embryonic stem
      cells (hESCs) by manually selecting specifically sized and shaped spheres
      followed by fluorescence-activated cell sorting based on the relative cell size.
      In addition, we report that labeling of hNPCs with ultra-small superparamagnetic
      iron oxide (USPIO) particles does not affect the cellular morphology or growth.
      More importantly, we show that the transduction with lentiviral vector encoding
      green fluorescent protein (GFP) decreases the neurality of the cell population.
      We conclude that our cost-effective protocol of generating hNPCs is widely
      applicable for preclinical studies on CNS disorders. This improved method of
      producing large quantities of high-purity hNPCs maybe useful also when generating
      hNPCs from human induced pluripotent stem (hiPS) cell lines. However, caution
      should be used when lenti-GFP transduction is applied for hNPC labeling. 

PMID- 23127330
TI  - Automaticity in social-cognitive processes.
AB  - Over the past several years, the concept of automaticity of higher cognitive
      processes has permeated nearly all domains of psychological research. In this
      review, we highlight insights arising from studies in decision-making, moral
      judgments, close relationships, emotional processes, face perception and social
      judgment, motivation and goal pursuit, conformity and behavioral contagion,
      embodied cognition, and the emergence of higher-level automatic processes in
      early childhood. Taken together, recent work in these domains demonstrates that
      automaticity does not result exclusively from a process of skill acquisition (in
      which a process always begins as a conscious and deliberate one, becoming capable
      of automatic operation only with frequent use) - there are evolved substrates and
      early childhood learning mechanisms involved as well.

PMID- 23127331
TI  - Directional cell migration through cell-cell interaction on polyelectrolyte
      multilayers with swelling gradients.
AB  - The directional cell migration plays a crucial role in a variety of physiological
      and pathological processes. It can be controlled by the gradient cues immobilized
      on the substrate. The poly(sodium 4-styrenesulfonate)
      (PSS)/poly(diallyldimethylammonium) chloride (PDADMAC) multilayers were post
      treated in a gradient NaCl solution with a concentration ranging from 3 M to 5 M,
      yielding the gradient multilayers with a similar chemistry composition (PSS
      domination) but gradually changed swelling ratio. The gradient nature and
      physicochemical properties were characterized by X-ray photoelectron spectroscopy
      and ellipsometry. Compared to the random migration with a lower rate at a smaller
      cell-seeding density, the vascular smooth muscle cells migrated directionally to
      the low hydration side at an appropriate cell-seeding density (1.5 * 10(4)/cm(2))
      under the assistance of cell-cell interactions. The cell migration rates on the
      gradient surface were significantly larger than those on the corresponding
      uniform surfaces etched by salt solutions of the same concentrations. Relative
      cell adherent strength and focal adhesion formation were studied to unveil the
      intrinsic mechanism of the gradient multilayers on the cell migration. It was
      found that both the gradient cues and cell-cell contact have major influences on
      the directional cell migration.

PMID- 23127332
TI  - Anti-tumor and anti-angiogenic effect of metronomic cyclic NGR-modified liposomes
      containing paclitaxel.
AB  - In the present study, we prepared NGR-modified sterically stabilized liposomes
      containing paclitaxel (NGR-SSL-PTX) in order to evaluate their potential
      targeting to aminopeptidase N receptors expressed on tumor endothelial cells and
      the tumor cell surface and its anti-angiogenic activity following metronomic
      administration. NGR-SSL-PTX was prepared by a thin-film hydration method. The in
      vitro targeting characteristics of NGR-modified liposomes on HUVEC (human
      umbilical vein endothelial cells), HT1080 (human fibrosarcoma cells) and MCF-7
      (human breast adenocarcinoma cells) were then investigated. The effect of NGR-SSL
      PTX on HUVEC proliferation and migration was also tested. The pharmacokinetics of
      NGR-SSL-PTX was studied in rats. The in vivo targeting activity of NGR-modified
      liposomes was investigated in HT1080 tumor-bearing mice. The anti-tumor activity
      of NGR-SSL-PTX following metronomic administration was evaluated in HT1080 tumor
      bearing mice in vivo. The targeting activity of the NGR-modified liposomes was
      demonstrated by in vitro flow cytometry and confocal microscopy as well as in
      vivo confocal immunofluorescence microscopy and bio-distribution experiments. The
      results of endothelial cell proliferation and migration and microvessel density
      (MVD) confirmed the anti-angiogenic activity of NGR-SSL-PTX in vitro and in vivo.
      The sustained circulation of NGR-SSL-PTX was shown in the pharmacokinetic study.
      NGR-SSL-PTX is able to improve treatment efficacy producing the most significant
      anti-tumor activity and anti-angiogenic following metronomic administration.

PMID- 23127333
TI  - The inhibition of human bladder cancer growth by calcium carbonate/CaIP6
      nanocomposite particles delivering AIB1 siRNA.
AB  - Previously, we reported that inorganic amorphous calcium carbonate (ACC) hybrid
      nanospheres functionalized with Ca(II)-IP6 compound (CaIP6) is a promising gene
      vector in vitro. Here, nonviral gene carrier, ACC/CaIP6 nanocomposite particles
      (NPACC/CaIP6), was evaluated for efficient in vitro and in vivo delivery of small
      interfering RNA (siRNA) targeting human Amplified in breast cancer 1 (AIB1). The
      nanoparticle is capable of forming ACC/CaIP6 nanoparticle-siRNA complexes and
      transferring siRNA into targeted cells with high transfection efficiency.
      Meanwhile the ACC/CaIP6 nanoparticle-siRNA complexes have no obvious cytotoxicity
      for human bladder cancer T24 cells. Furthermore, NPACC/CaIP6 effectively
      protected the encapsulated siRNA from degradation, AIB1 knockdown mediated by
      ACC/CaIP6/siRNA complexes transfection resulted in cells proliferation
      inhibition, apoptosis induction and cell cycle arrest in vitro. NPACC/CaIP6
      exhibited well tissues penetrability in localized siRNA delivering, intratumoral
      injection of NPACC/CaIP6/siAIB1 could attenuate tumor growth and downregulation
      of PI3K/Akt signaling pathway in vivo. We conclude that ACC/CaIP6 nanoparticle is
      a promising system for effective delivery of siRNA for cancer gene therapy.

PMID- 23127334
TI  - Polyethyleneimine/DNA polyplexes with reduction-sensitive hyaluronic acid
      derivatives shielding for targeted gene delivery.
AB  - The natural anionic polysaccharide hyaluronic acid (HA) was modified by
      introducing reduction-sensitive disulfide bond between the carboxyl groups and
      the backbone of HA (HA-SS-COOH). HA-SS-COOH and its corresponding unmodified
      stable analog HA were used to shield DNA/PEI polyplexes (DP) to form ternary
      complexes (DPS and DPH complexes). The shielding/deshielding effect was tested
      along with size, zeta potential, cell viability and transfection. Both DPS and
      DPH complexes showed increase in size, decrease in zeta potential and low
      cytotoxicity in physiological conditions due to the anionic shielding. In the
      reductive environment, only HA-SS-COOH coated ternary complexes (DPS)
      demonstrated the size increase and recovered high positive zeta potential. DPS
      complexes showed an up to 14-fold higher transfection than the stable coated one,
      indicating the efficiency of the reduction-responsive deshielding design.
      Moreover, the presence of extra free HA inhibited the transfection of DPS on
      HepG2 and B16F10 cells with HA receptor expression, while displaying no effect on
      non-targeted NIH3T3 cells. More rapid cellular association of DPS with HepG2 was
      observed, thus confirming the targeting reservation of disulfide bond modified
      HA. Intratumoral injection of DPS complexes resulted in much higher accumulation
      and luciferase expression in the tumor bearing C57BL/6 mice. Both in vitro and in
      vivo results demonstrated the successful combination of deshielding and target
      functions in HA derivatives for gene delivery.

PMID- 23127335
TI  - A comparison of human cord blood- and embryonic stem cell-derived endothelial
      progenitor cells in the treatment of chronic wounds.
AB  - Endothelial progenitor cells (EPCs) promote new blood vessel formation and
      increase angiogenesis by secreting growth factors and cytokines in ischemic
      tissues. Therefore, EPCs have been highlighted as an alternative cell source for
      wound healing. EPCs can be isolated from various sources, including the bone
      marrow, cord blood, and adipose tissue. However, several recent studies have
      reported that isolating EPCs from these sources has limitations, such as the
      isolation of insufficient cell numbers and the difficulty of expanding these
      cells in culture. Thus, human embryonic stem cells (hESCs) have generated great
      interest as an alternative source of EPCs. Previously, we established an
      efficient preparation method to obtain EPCs from hESCs (hESC-EPCs). These hESC
      EPCs secreted growth factors and cytokines, which are known to be important in
      angiogenesis and wound healing. In this study, we directly compared the capacity
      of hESC-EPCs and human cord blood-derived EPCs (hCB-EPCs) to benefit wound
      healing. The number of hESC-EPCs increased during culture and was always higher
      than the number of hCB-EPCs during the culture period. In addition, the levels of
      VEGF and Ang-1 secreted by hESC-EPCs were significantly higher than those
      produced by hCB-EPCs. After transplantation in a mouse dermal excisional wound
      model, all EPC-transplanted wounds exhibited better regeneration than in the
      control group. More importantly, we found that the wounds transplanted with hESC
      EPCs showed significantly accelerated re-epithelialization. Thus, hESC-EPCs may
      be a promising cell source for the treatment of chronic wounds.

PMID- 23127336
TI  - Studies of mixed liposomes with novel sorbyl functionalized head group lipids.
AB  - Three novel polymerizable amphiphiles with a sorbyl-substituted head group were
      synthesized and systematically characterized. These amphiphiles are neutral in
      charge. None of these molecules forms vesicles by itself, presumably due to lack
      of amphiphilicity and/or extensive head group interaction. Therefore, mixed
      vesicles were formed with other fluid lipids such as DPenPC, eggPC, or DOPC. We
      investigated the properties of these mixtures in both vesicles and Langmuir
      films. The Langmuir isotherms show formation of monolayers by all three
      molecules. However, the isotherms for mixed monolayers suggest that two
      components are largely immiscible to the mixing lipid. Under polymerization
      conditions, mixed vesicles of these amphiphiles form oligomers, suggesting that
      in spite of a larger head group, they form mesophases.

PMID- 23127337
TI  - Psf3 is a prognostic biomarker in lung adenocarcinoma.
AB  - Psf3 is a member of the evolutionarily conserved heterotetrameric complex GINS
      (Go-Ichi-Ni-San), which consists of Sld5, Psf1, Psf2, and Psf3. Previous studies
      have suggested that some GINS complex members are upregulated in cancer, but the
      status of Psf3 expression in lung adenocarcinoma has not been investigated. The
      objective of the current study was to determine whether Psf3 plays a role in lung
      adenocarcinoma by investigating clinical samples. We investigated the status of
      Psf3 expression in cancer cells of 125 consecutive resected lung adenocarcinomas
      by immunohistochemistry. Increased Psf3 expression was observed in 27 (21.6%) of
      the 125 cases. Further, univariate analysis and log-rank test indicated a
      significant association between Psf3 expression and lower overall survival rate
      (P = 0.0001 and P < 0.0001, respectively). Multivariate analysis also indicated a
      statistically significant association between increased Psf3 expression and lower
      overall survival rate (hazard ratio, 5.2; P = 0.0027). In a subgroup analysis of
      only stage I patients, increased Psf3 expression was also significantly
      associated with a lower overall survival rate (P = 0.0008, log-rank test).
      Moreover, the Ki67 index level was higher in the Psf3-positive group than in the
      Psf3-low positive group (P < 0.0001, Mann-Whitney U-test). Our results indicated
      that Psf3 can serve as a prognostic biomarker in lung adenocarcinoma.

PMID- 23127338
TI  - The A/G allele of eIF3a rs3740556 predicts platinum-based chemotherapy resistance
      in lung cancer patients.
AB  - eIF3a is the largest subunit of eukaryotic translation initiation factor 3, which
      has been suggested to affect tumor progression and activity of nucleotide
      excision repair pathway contributing to platinum resistance. The purpose of this
      study was to investigate possible mutations in promoter and exon regions of eIF3a
      gene and to assess whether eIF3a mutation status have prognostic and predictive
      significance in platinum-based chemotherapeutic lung cancer patients. 771 lung
      cancer patients were enrolled and followed up. These patients were newly
      diagnosed with incident lung cancer, which was confirmed histologically or
      cytologically, and accepted platinum-based chemotherapy for at least two cycles.
      Three novel mutations of eIF3a were found, including 11279G>A in intron 6,
      Arg438Lys in exon 9, 29671G>A in intron 15, with minor allele frequency of 0.16,
      0.18, 0.16, respectively. A-carrier patients of rs3740556 conferred a
      significantly better platinum-based chemotherapy response (p < 0.05) and seemed
      to live longer. eIF3a genetic polymorphisms can be considered as predictive tools
      for pretreatment evaluation of platinum-based chemotherapy. Lung cancer patients
      carrying rs3740556 A allele tended to have a favorable prognosis after treatment
      with platinum-based chemotherapy.

PMID- 23127339
TI  - Vacuum-assisted core biopsy in diagnosis and treatment of intraductal papillomas.
AB  - BACKGROUND: The aim of this study was to assess the value of mammographically
      guided and ultrasonographically-guided vacuum-assisted core biopsy (VACB) in the
      diagnosis and treatment of intraductal papillomas of breast and to answer the
      question of whether biopsy with the Mammotome (Mammotome; Cincinnati, OH) allows
      the avoidance of surgery in these patients. PATIENTS AND METHODS: In the period
      2000 to 2010, a total of 1896 vacuum-assisted core biopsies were performed, of
      which 1183 were ultrasonographically guided and 713 were mammographically guided
      (stereotaxic). RESULTS: In 62 patients (3.2%) histopathologic examination
      confirmed intraductal papilloma, and in 12 patients (19.4%) atypical lesions were
      also found. Open surgical biopsy specimens revealed invasive cancer in 2 women
      these 12 women (false-negative rate, 16.7%; negative predictive value, 83.3%).
      Biopsy specimens from the remaining 50 patients (80.6%) revealed papilloma
      without atypia, and further clinical observation and imaging examinations did not
      show recurrence or malignant transformation of lesions. Hematoma developed in 3
      (4.8%) patients as a complication of biopsy; surgical intervention was not
      required in any of the patients. CONCLUSION: VACB is a minimally invasive and
      efficient method for diagnosing intraductal papilloma of the breast. If
      histopathologic examination confirms a benign lesion and corresponds to the
      clinical presentation, surgery may be avoided. However in all cases,
      histopathologic diagnosis of papilloma with atypical hyperplasia or a suspected
      malignant lesion in imaging examinations, despite negative biopsy results, should
      always be an indication for surgical excision.

PMID- 23127340
TI  - Breast cancer stem cells: a novel therapeutic target.
AB  - Breast cancer stem cells (BCSCs), characterized by the CD44(+)/CD24(-/low)
      marker, are attributed with features that are demonstrated by the disease itself,
      such as growth of tumor, recurrence, metastases, and multiple drug resistance.
      This review concerns the emergence and expediency of BCSCs in treating relapse
      and advanced cases of breast cancer. One of the ideal ways of detecting and
      eliminating BCSCs would be to tweak certain molecular receptors in the desired
      pathway, which would require extensive and comprehensive knowledge about these
      cell signaling pathways. Although hedgehog (Hh), Notch, and Wnt signaling are of
      prime concern, governing tumorigenesis and cancer stem cell (CSC) renewal,
      designing chemotherapeutic or molecular targeted therapies is still a tricky
      arena to venture into, as these pathways play a vital role in normal mammary
      gland development. Thus selective inhibition of pathway receptors needs to be
      investigated in the future.

PMID- 23127341
TI  - The diagnosis and treatment of neonatal seizures.
AB  - The occurrence of neonatal seizures is an important clinical sign indicating
      brain disorder in neonates. An identification of neonatal seizures is critical in
      the management of high risk neonates. However, the diagnosis and management of
      neonatal seizures are challenging, because electroclinical dissociation is an
      outstanding feature of neonatal seizures. Neonatal seizures are frequently not
      accompanied by any identifiable clinical symptoms even on close observation,
      whereas motor phenomena which have been considered to be seizures are not
      associated with ictal electroencephalography (EEG) correlates. For this reason,
      neonatal seizures should be diagnosed based on ictal EEG findings and the
      efficacy of treatment should be evaluated using continuous EEG monitoring. EEG is
      also useful diagnosing the underlying etiology of neonatal seizures. Although
      conventional EEG is the gold standard for the diagnosis of neonatal seizures,
      amplitude-integrated EEG (aEEG) can be considered an option. However, aEEG has
      substantial limitations. In treatment two aspects must be considered. First,
      neonatal seizures themselves require emergency therapy and second, etiology
      specific therapy is important in order to prevent further brain injury. At
      present, evidence is limited on the treatment of neonatal seizures. In order to
      establish effective treatment, studies using continuous EEG/aEEG monitoring and
      long-term follow-up are necessary. Widespread use of EEG/aEEG is desirable in
      order to solve several problems in the diagnosis and treatment of neonatal
      seizures.

PMID- 23127342
TI  - Comparison of respiratory parameters and plasma cytokine levels between treatment
      with Salmeterol/fluticasone and ipratropium/terbutaline/budesonide in
      mechanically ventilated COPD patients.
AB  - BACKGROUND: It is unknown whether the bronchodilation and anti-inflammatory
      effects of inhaled salmeterol and fluticasone (SF) are better than those of
      traditionally inhaled ipratropium, terbutaline and budesonide (ITB) in
      mechanically ventilated patients with chronic obstructive pulmonary disease
      (COPD). METHODS: Nineteen stable COPD patients with respiratory failure were
      randomly enrolled into two groups. Patients were treated with inhaled SF
      delivered by a metered-dose inhaler with a spacer or with inhaled nebulized ITB.
      Respiratory parameters were measured for 7 days and plasma cytokine levels were
      measured on days 1 and 7. RESULTS: The kinetic curve of the rapid shallow index
      (RSI) from day 1 to day 7 was significant lower in the SF group than that in the
      ITB group. There were no significant differences in minute ventilation, intrinsic
      positive end expiratory pressure, and airway resistance between the ITB and SF
      groups from day 1 to day 7. There were no differences in plasma interleukin (IL)
      6, IL-10, IL- 12, and transforming growth factor-beta1 levels between day 1 and
      day 7 in the ITB or SF group. CONCLUSIONS: Patients with inhaled SF treatment had
      a lower RSI. The effects of bronchodilators and anti-inflammation were similar
      between inhaled SF and ITB in COPD patients with ventilator support.

PMID- 23127343
TI  - Serum lipid profile could predict the inception and impacts of violent behaviors
      among acute psychiatric inpatients.
AB  - BACKGROUND: The prediction of violence among psychiatric inpatients using
      biophysiological indicators is warranted for re-examinations longitudinally. This
      study aims to explore factors associated with the occurrence of violence and
      subsequent medical impacts in psychiatric inpatients. METHODS: Inpatients
      diagnosed with either schizoaffective disorder or bipolar mania were admitted to
      acute wards in a professional psychiatric care setting. A longitudinal analysis
      was applied to construct predictive models with blood biochemistry tests upon
      admission. Medical records and an administrative database were used for analyses.
      RESULTS: Triglycerides were found to be a significant predictor of violence
      inception, which demonstrated a multivariate-adjusted odds ratio of 0.988 per
      mg/dL increment. Psychiatric inpatients with a higher level of triglycerides were
      less likely to have violent behaviors while more serious medical impacts were
      found once violence occurred. The elevated medical expenses derived from violence
      were negatively correlated with the level of cholesterol upon admission. A U
      shape relationship was found between medical impacts and the combination of serum
      triglycerides and cholesterol. CONCLUSION: The study provides useful predictors
      for early pre-screening of potential violence cases among acute psychiatric
      inpatients and therefore offers various angles for future strategic management of
      care plans in psychiatric medical settings.

PMID- 23127344
TI  - Factors associated with strain in informal caregivers of stroke patients.
AB  - BACKGROUND: Stroke is one of the most prevalent causes of adult disability and
      handicap. Informal caregivers play an important role in poststroke care. However,
      informal caregivers may experience strain, which threatens the recovery of stroke
      subjects. This study aimed to describe changes in strain experienced by informal
      caregivers from 3 to 6 months after the stroke, and identify the predicting
      factors. METHODS: We recruited pairs of inpatients with ischemic stroke and
      informal caregivers from a tertiary referral hospital and interviewed them at 3
      and 6 months after the stroke. Caregiver strain was evaluated using the Caregiver
      Strain Index (CSI), with a CSI >= 7 indicating considerable caregiver strain.
      Various factors associated with caregiver strain were analyzed using generalized
      estimating equations. RESULTS: Eighty-nine stroke patients and caregivers
      completed the study. Considerable strain was reported in 46% and 43% of the
      caregivers at the 3rd and 6th month, respectively. Patient factors such as severe
      disabilities (Barthel Index <= 60), poor cognition (Mini-Mental State Examination
      <= 23), depression (Beck Depression Inventory [BDI] >= 10), and recurrent stroke
      were predictors for caregiver strain. Caregiver factors, such as changed
      employment status, help from formal caregivers, and depression (BDI >= 10) were
      also associated with considerable caregiver strain. CONCLUSIONS: Nearly 50% of
      caregivers experienced considerable strain. Interventions aimed at reducing the
      caregivers' strain should focus on enhancing the functional and emotional status
      of stroke subjects, prevention of recurrent stroke, and efficient management of
      depression symptoms in caregivers.

PMID- 23127345
TI  - Everolimus in metastatic renal cell carcinoma: preliminary experience from Chang
      Gung Memorial Hospital.
AB  - BACKGROUND: Everolimus has been approved for second-line treatment of patients
      with metastatic renal cell carcinoma (mRCC) after failure of sorafenib or
      sunitinib. The purpose of this retrospective study was to assess the efficacy and
      safety of everolimus in Taiwanese patients with mRCC. METHODS: Between March 2009
      and August 2011, 24 mRCC patients treated with everolimus were analyzed. Prior to
      everolimus, each patient had received therapy with at least one vascular
      endothelial growth factor receptor-tyrosine kinase inhibitor. Progression-free
      survival (PFS) and overall survival (OS) were estimated according to the Kaplan
      Meier method. RESULTS: Fifteen patients (62.5%) achieved stable disease. The
      median PFS was 7.1 months (95% confidence interval, 3.6-10.5 months). The median
      OS was 20.7 months (95% confidence interval, 5.0-36.4 months). The most frequent
      non-hematologic adverse events with everolimus were mucositis, rash, epistaxis
      and pneumonitis. CONCLUSIONS: Everolimus is an effective second-line treatment
      for Taiwanese patients with mRCC. The toxicity is tolerable and manageable.

PMID- 23127346
TI  - Team innovation climate and knowledge sharing among healthcare managers:
      mediating effects of altruistic intentions.
AB  - BACKGROUND: This paper aims to provide empirical evidence concerning the impact
      of team climate on knowledge sharing behavior and the mediating effects of
      individuals' altruistic intentions in the context of healthcare settings.
      METHODS: Questionnaire data were collected from 212 administrators employed at a
      medical center in Taiwan. Team climate was assessed by the Team Climate Inventory
      composed of four factors, participative safety, support for innovation, vision,
      and task orientation. The proposed hypotheses were tested using structural
      equation modeling. RESULTS: The influence of the team innovation climate on
      knowledge sharing behavior was evident. Furthermore, individuals' altruistic
      intentions played a full mediating role in the relationship between team
      innovation climate and knowledge sharing behavior. CONCLUSIONS: These results
      contribute to the field of the people-orientated perspective in knowledge
      management. The full mediating effect of employees' altruistic intentions
      provides healthcare team managers the direction to accelerate knowledge sharing
      behavior.

PMID- 23127347
TI  - Chemotherapy with gemcitabine plus cisplatin in patients with advanced biliary
      tract carcinoma at Chang Gung Memorial Hospital: a retrospective analysis.
AB  - BACKGROUND: A gemcitabine-cisplatin combination is a standard treatment option
      for patients with advanced biliary tract carcinoma (BTC). We assessed the
      efficacy and safety of this regimen at Chang Gung Memorial Hospital. METHODS:
      Between April 2009 and December 2010, 30 chemotherapy-naive patients (13 men and
      17 women; median age: 61.5 years) with advanced BTC were retrospectively
      analyzed. Treatment consisted of gemcitabine (Gemmis((r)); TTY, Taipei, Taiwan)
      1000 mg/m(2), followed by cisplatin 30 mg/m(2) on days 1 and 8 every 3 weeks.
      Tumor response was evaluated using the Response Evaluation Criteria in Solid
      Tumors (RECIST) criteria every 2-3 cycles. The toxicity was assessed by the
      National Cancer Institute Common Terminology Criteria for Adverse Events, Version
      3. RESULTS: At the end of July, 2011, 27 patients were evaluated using the RECIST
      criteria. According to the intent to treat analysis of response, 5 patients
      (16.7%) had a partial response, 10 patients (33.3%) had stable disease and 12
      patients (40.0%) had progressive disease. The median time to progression (TTP)
      and median overall survival (OS) of the 30 patients were 4.8 months and 13.4
      months, respectively. The patients with biliary obstruction requiring drainage
      before treatment had a significantly shorter OS than those without biliary
      obstruction (p = 0.02) even though the TTP showed no statistically significant
      difference (p = 0.69) between groups. The major grade III/IV adverse events in
      the 30 patients included infection (n = 8, 26.7%), anemia (n = 5, 16.7%),
      neutropenia (n = 4, 13.3%), and elevated alanine aminotransferase (n = 2, 6.7%).
      There were no treatment-related deaths. CONCLUSIONS: Gemcitabine plus cisplatin
      is a feasible chemotherapy regimen with manageable toxicity in patients with
      advanced BTC. Maintaining good biliary drainage is essential for these patients.

PMID- 23127348
TI  - Leiomyosarcoma of the adrenal vein.
AB  - Leiomyosarcoma of the adrenal gland is extremely rare in the literature. We
      present a patient with an adrenal leiomyosarcoma originating from the adrenal
      vein, the pathologic findings and management. A 66-year-old man who was a
      hepatitis B virus carrier was found to have a huge left suprarenal mass on
      sonography and computed axial tomography. A huge tumor in the left suprarenal
      area with a markedly engorged adrenal vein was found during an adrenalectomy. The
      tumor thrombus extended into the renal vein, close to the inferior vena cava. The
      left adrenal gland with the whole tumor thrombus was removed completely.
      Microscopically, the adrenal gland was compressed but not invaded by the spindle
      cell tumor, which was composed of interlacing fascicles of neoplastic smooth
      muscle cells. The tumor was localized within the adrenal vein and arose from the
      venous wall. The patient had no local recurrence for 18 months after en bloc
      excision of the tumor. We suggest that en bloc excision with a clear and adequate
      surgical margin is the most important cure procedure for adrenal leiomyosarcoma.

PMID- 23127349
TI  - Enhanced serodiagnostic utility of novel Mycobacterium tuberculosis polyproteins.
AB  - OBJECTIVES: The detection of Mycobacterium tuberculosis specific antibodies in
      human sera has been a rapid and important diagnostic aid for tuberculosis (TB)
      control and prevention. However, any single antigen is not enough to be used to
      cover the antibody profiles of all TB patients. METHODS: Seven single antigens
      (38 kDa, ESAT-6, CFP10, Mtb8.4, MPT64, TB16.3 and Mtb8) were evaluated
      serodiagnostically. Two novel M. tuberculosis polyproteins, 38kD-ESAT6-CFP10
      (38F) and Mtb8.4-MPT64-TB16.3-Mtb8 (64F), were expressed and the novel 38F-64F
      indirect ELISA assay used to analyze antibody responses to polyproteins in serum
      samples. RESULTS: The sensitivity of the novel 38F-64F indirect ELISA alone was
      much higher than that of the sputum culture test (86.91% vs. 50.62%) and that of
      the sputum smear test (78.64% vs. 47.57%). The novel 38F-64F indirect ELISA had a
      sensitivity of 74.16% with sera from extrapulmonary TB patients and a sensitivity
      of 37.14% with sera from LTBI. The specificity of the novel 38F-64F indirect
      ELISA was 90.36% with the sera from healthy blood donors and 94.15% with the sera
      from non-TB patients. CONCLUSIONS: The novel 38F-64F indirect ELISA assay had
      effective diagnostic performance and would make meaningful contribution to the
      diagnosis of TB disease in developing countries.

PMID- 23127351
TI  - Dyadic coping, insecure attachment, and cortisol stress recovery following
      experimentally induced stress.
AB  - Evidence for the stress-buffering effects of social support in intimate
      relationships raises important questions about whether partner support promotes
      recovery in physiological systems implicated in physical health. The present
      study examined (a) whether observed dyadic coping enhances cortisol stress
      recovery and (b) whether a stressed partner's self-reported attachment anxiety
      and avoidance moderate these effects. Stress was experimentally induced by asking
      either the man or woman in 123 heterosexual couples to participate in a
      standardized public speaking task. Stressed individuals recovered faster from
      stress the more positive dyadic coping they received from the partner, with women
      high in attachment anxiety benefiting less from these behaviors. Attachment
      avoidance did not moderate these associations. This study highlights the value of
      examining the interplay between partners' behaviors and attachment orientations
      in order to understand the impact of stress on close relationships and partners'
      health.

PMID- 23127352
TI  - Emotional congruence within couple interaction: the role of attachment avoidance.
AB  - Attachment strategies refer to the conscious representations individuals make of
      their relationships, including the level of perceived comfort and safety that
      relationships offer during distressing times. From early in life, some
      individuals learn the coping strategy of attachment avoidance. When distressed,
      these individuals shut down emotionally and seek to mask what they are feeling.
      This represents incongruence between emotional experience and expression. Yet
      congruence is an important part of interpersonal relationships. In addition,
      incongruence has been identified as a core aspect of repressive coping, about
      which research has identified several potential long-term health risks. In this
      study, we examined the relationship between attachment avoidance and congruence
      between what individuals experience physiologically and what they report. A total
      of 63 couples completed the Experiences in Close Relationships Scale (ECR;
      Brennan, Clark, & Shaver, 1998) and participated in a seminatural couple
      interaction and an interaction with a therapist/coach. Using dyadic data analysis
      and multilevel modeling, we found that, while avoidance was not associated with
      elevated skin conductance, it was indeed associated with greater incongruence
      between skin conductance and reports of feelings toward one's partner. Whereas
      individuals lower in attachment avoidance were likely to report more negative
      feelings toward their partners in the context of psychophysiological distress,
      those higher in attachment avoidance were more likely to report positive feelings
      toward their partners. We discuss implications of this incongruence and its
      potential to adversely influence individual and relationship health. We also
      discuss some important clinical considerations when working to increase emotional
      congruence.

PMID- 23127350
TI  - The duration and timing of maternal depression as a moderator of the relationship
      between dependent interpersonal stress, contextual risk and early child
      dysregulation.
AB  - BACKGROUND: Risk factors that are associated with depression in the mother also
      negatively affect the child. This research sought to extend current knowledge by
      examining the duration and timing of maternal depression as a moderator of: (1)
      the impact of dependent interpersonal stress (DIS), such as partner conflict or
      low social support, and contextual risk (e.g. poverty) on child dysregulation;
      and (2) continuity in early child dysregulation. METHOD: Mother-child pairs (n =
      12 152) who participated in the Avon Longitudinal Study of Parents and Children
      (ALSPAC) were examined between pregnancy and age 4 years. Data on maternal
      depression were collected five times between pregnancy and 33 months postpartum;
      on DIS and contextual risk three times between pregnancy and 33 months; and on
      child dysregulation at age 2 and 4 years. RESULTS: Longitudinal latent class
      analysis identified a class of mothers (10%) who evinced a chronic level of
      depression between pregnancy and 33 months. For chronic-depressed versus non
      depressed mothers, the results indicate that: (1) DIS predicted higher child
      dysregulation if experienced between pregnancy and age 2; (2) contextual risk had
      a differential effect on child dysregulation if experienced during pregnancy; and
      (3) children had higher continuity in dysregulation between age 2 and age 4.
      CONCLUSIONS: Assessing the impact of the timing and duration of maternal
      depression, and different types of co-occurring risk factors, on child well-being
      is important. Maternal depression and associated DIS, in comparison to contextual
      risk, may be more responsive to intervention.

PMID- 23127353
TI  - An antimicrobial stewardship program improves antimicrobial treatment by culture
      site and the quality of antimicrobial prescribing in critically ill patients.
AB  - INTRODUCTION: Increasing antimicrobial costs, reduced development of novel
      antimicrobials, and growing antimicrobial resistance necessitate judicious use of
      available agents. Antimicrobial stewardship programs (ASPs) may improve
      antimicrobial use in intensive care units (ICUs). Our objective was to determine
      whether the introduction of an ASP in an ICU altered the decision to treat
      cultures from sterile sites compared with nonsterile sites (which may represent
      colonization or contamination). We also sought to determine whether ASP education
      improved documentation of antimicrobial use, including an explicit statement of
      antimicrobial regimen, indication, duration, and de-escalation. METHODS: We
      retrospectively analyzed consecutive patients with positive bacterial cultures
      admitted to a 16-bed medical-surgical ICU over 2-month periods before and after
      ASP introduction (April through May 2008 and 2009, respectively). We evaluated
      the antimicrobial treatment of positive sterile- versus nonsterile-site cultures,
      specified a priori. We reviewed patient charts for clinician documentation of
      three specific details regarding antimicrobials: an explicit statement of
      antimicrobial regimen/indication, duration, and de-escalation. We also analyzed
      cost and defined daily doses (DDDs) (a World Health Organization (WHO)
      standardized metric of use) before and after ASP. RESULTS: Patient demographic
      data between the pre-ASP (n = 139) and post-ASP (n = 130) periods were similar.
      No difference was found in the percentage of positive cultures from sterile sites
      between the pre-ASP period and post-ASP period (44.9% versus 40.2%; P = 0.401). A
      significant increase was noted in the treatment of sterile-site cultures after
      ASP (64% versus 83%; P = 0.01) and a reduction in the treatment of nonsterile
      site cultures (71% versus 46%; P = 0.0002). These differences were statistically
      significant when treatment decisions were analyzed both at an individual patient
      level and at an individual culture level. Increased explicit antimicrobial
      regimen documentation was observed after ASP (26% versus 71%; P < 0.0001). Also
      observed were increases in formally documented stop dates (53% versus 71%; P <
      0.0001), regimen de-escalation (15% versus 23%; P = 0.026), and an overall
      reduction in cost and mean DDDs after ASP implementation. CONCLUSIONS:
      Introduction of an ASP in the ICU was associated with improved microbiologically
      targeted therapy based on sterile or nonsterile cultures and improved
      documentation of antimicrobial use in the medical record.

PMID- 23127354
TI  - Assessment of prevalence and pathological response to orthostatic provocation in
      patients with multiple sclerosis.
AB  - OBJECTIVE: The aim of this study was to determine the prevalence of pathologic
      response to orthostatic challenge in patients with relapsing remitting multiple
      sclerosis (RRMS) and the difference of the response in patients in relapse and
      remission. PATIENTS AND METHODS: We included 112 RRMS patients; group 1 included
      53 patients in a relapse and group 2, 59 patients in remission. The head up tilt
      table test was used to provoke an orthostatic reaction. RESULTS: 71 (63%)
      patients (60.4% and 66% of relapse and remission subjects respectively) had a
      pathological response to orthostatic provocation. Syncope was found in 9 (17%)
      patients in group 1 compared to 22 (37.3%) in group 2 (p=0.014). Postural
      orthostatic tachycardia syndrome (POTS) was found in 17 (32%) patients in group 1
      compared to 4 (6.8%) in group 2 (p=0.001). There was a significantly negative
      correlation between the Expanded Disability Status Scale (EDSS) and POTS (-0.201;
      p=0.034) and a positive correlation between the EDSS and syncope (0.190;
      p=0.044). CONCLUSION: The prevalence of distinct types of orthostatic autonomic
      dysfunction in different phases of RRMS seems to be in direct correlation with
      the EDSS. Furthermore, certain autonomic dysfunctions of orthostasis, more
      specifically syncope and POTS, tend to be increased in remission and relapse
      respectively.

PMID- 23127355
TI  - Technical application and the level of discomfort associated with an
      intramuscular electromyographic investigation into gluteus minimus and gluteus
      medius.
AB  - Our current theoretical understanding of gluteus minimus (GMin) and gluteus
      medius (GMed) function is primarily based on cadaveric studies and biomechanical
      modelling. There is an absence of electromyographic (EMG) research that aims to
      verify this understanding, particularly in relation to the potentially unique
      functional roles of structurally distinct segments within GMin (anterior and
      posterior) and GMed (anterior, middle and posterior). The aim of this paper is to
      provide a comprehensive technical description for inserting intramuscular EMG
      electrodes into uniquely oriented segments of GMin and GMed; and to report the
      levels of discomfort associated with gluteal intramuscular electrode insertions.
      Fifteen healthy volunteers took part in a series of walking trials after
      intramuscular EMG electrodes were inserted into segments of GMin (*2) and GMed
      (*3) according to previously verified guidelines. Visual analogue scores
      following walking trials at comfortable and fast speed indicate that discomfort
      levels associated with these insertions were low (2.4+/-1.4 and 1.6+/-0.7
      respectively). The technical descriptions and illustrations provided in this
      paper will allow trained intramuscular electromyographers to insert electrodes
      into these muscle segments with confidence.

PMID- 23127356
TI  - Identification of the genomic BCR-ABL1 fusion sequence from blood specimen stored
      on filter paper.
AB  - Chronic myeloid leukaemia (CML) is characterized by the Philadelphia chromosome
      resulting in the BCR-ABL1 gene whose mRNA transcript detection is commonly used
      for diagnosis and monitoring of therapeutic response. However, in collected blood
      specimen degradation of mRNA has to be considered during storage and transport
      thus jeopardizing the analysis. We here describe an alternative DNA-based
      technique applied after long-term blood storage. DNA was isolated from dried
      blood stains from CML patients stored on filter paper (Guthrie cards) after a
      median period from diagnosis of 11 years (range: 5-12 years) and analyzed with a
      two round long-range multiplex PCR (MLR-PCR) to identify the genomic BCR-ABL1
      breakpoint. Patient-specific individual BCR-ABL1 fusion sites were successfully
      detected in 10 out of 13 patients. Dried blood stains represent a valuable
      resource for genomic DNA analyses. Long term preservation is easily manageable in
      paper envelopes with the patient's medical files with a minimum of financial
      costs and efforts. Such the cooperation between laboratories and hospitals
      separated by long distances is facilitated rendering possible offering
      specialized genomic analyses to patients with CML virtually everywhere around the
      world. This technique may also be a valuable approach for diagnostic procedures
      on a high molecular level in related haematological malignancies.

PMID- 23127357
TI  - Increased circulating soluble LR11 in patients with acute coronary syndrome.
AB  - BACKGROUND: LR11 (also so called SorLA or SORL1) is a novel marker of intimal
      smooth muscle cell (SMC) proliferation. Vascular SMCs play important roles in the
      development of atherosclerosis interacting with macrophages in a vulnerable
      plaque of patients with acute coronary syndrome (ACS).The present study
      determines whether soluble LR11 (sLR11) is associated with ACS. METHODS: We
      studied 100 patients with coronary artery disease (CAD) comprising 50 consecutive
      patients with acute coronary syndrome (ACS; mean age 62.3+/-13.0 years; male
      78.0%) who were successfully treated with percutaneous coronary intervention and
      50 age- and sex-matched stable angina pectoris (SAP) patients as control.
      Concentration of sLR11 was measured by sandwich enzyme-linked immunosorbent assay
      method. RESULTS: Circulating sLR11 was significantly increased in patients with
      ACS compared with SAP (9.88+/-2.78 vs. 8.18+/-1.11 ng/ml, p<0.01). Multivariate
      logistic regression analysis indicated that sLR11 was independently associated
      with ACS (odds ratio (OR), sLR11 quartile increment, 2.18, 95% confidence
      interval (CI) 1.21-4.19, p<0.01). Among various biomarkers of acute coronary
      syndrome, hsCRP were significantly correlated with LR11 (r=0.480, p<0.01).
      CONCLUSIONS: There is a statistical significant association between LR11 and ACS
      and may be a useful biomarker for the development of acute coronary syndrome.

PMID- 23127358
TI  - Modeling methods for studying post-translational and transcriptional modifying
      enzymes.
AB  - Biological catalysis is a complex chemical process that involves not only
      electronic reorganization in the substrate but also the reorganization of the
      catalyst. This complexity is even larger in the case of post-transcriptional and
      post-translational modifications which may involve the interaction between two
      biomacromolecules. However, the development over the past decades of new
      computational methods and strategies is offering a detailed molecular picture of
      the catalytic event and a deep understanding of the mechanisms of chemical
      reactions in biological environments. Here we review the efforts made in the last
      years to model catalysis in post-transcriptional and post-translational
      processes. We stress on the advantages and problems of the different
      computational strategies and their applicability in different cases.

PMID- 23127359
TI  - Mechanisms of S-nitrosothiol formation and selectivity in nitric oxide signaling.
AB  - Although it is widely accepted that S-nitrosation occurs in vivo, questions
      remain regarding S-nitrosation as a signaling mechanism. The chemistry of S
      nitrosation includes NO oxidation to N(2)O(3) followed by reaction with
      thiolates, radical recombination of NO and thiyl radicals, and transition metal
      catalyzed pathways. Once formed, nitrosothiols can be transferred between small
      molecule or protein thiols through transnitrosation reactions. The pathways that
      lead to selective S-nitrosation of only a subset of cellular cysteines remain
      largely unknown. Selectivity may be conferred through colocalization with NOS
      isoforms, protein-protein interaction driven transnitrosation reactions,
      regulation of S-nitrosoglutathione levels, or directed denitrosation of protein
      nitrosothiols.

PMID- 23127360
TI  - Adverse event reporting in randomised controlled trials of neuropathic pain:
      considerations for future practice.
AB  - High-quality information on the potential benefit and harm of a drug is required
      for patients and clinicians to make informed treatment decisions and to enable
      cost-effectiveness modeling to be undertaken. This systematic review describes
      the collection and reporting of adverse event data as presented in published
      clinical trials of neuropathic pain for the evaluation of antidepressant or
      antiepileptic drugs. A total of 74 studies in 16,323 patients published between
      1965 and 2012 were identified, of which 43 were published from 2004 onwards. The
      review found that methods used to collect adverse event data, the frequency of
      collection, and the selection criteria used by authors for reporting adverse
      events vary substantially, and these events are often inadequately reported.
      Consequently, a potential synthesis of valuable harm information across trials is
      hampered. We make recommendations regarding the reporting of methods used to
      collect, assess, select, and present adverse event data in publications. Through
      the Core Outcome Measures in Effectiveness Trials (COMET) initiative, core
      outcome sets (which include effectiveness and harm) are developed by disease
      condition. To facilitate data synthesis for adverse events of drug therapies, we
      suggest that core outcome sets for harms could be developed by therapeutic class
      (ie, individualized for each class of drug). To improve comparability of
      information across trials collection methods need to be standardized for patient
      reports (spontaneous or prompted) and active surveillance (clinical examinations
      and laboratory tests). Uniform methods for presenting summary information
      regarding recurrent events, duration and timing of events requires further
      research.

PMID- 23127361
TI  - Debate from the 2012 ASH Annual Scientific Sessions: should blood pressure be
      reduced in hemodialysis patients? Con position.
AB  - The relationship between blood pressure and cardiovascular events in hemodialysis
      patients is complicated and controversial. The timing of blood pressure
      measurements (home, before dialysis, after dialysis, during dialysis) provide
      somewhat different results. Moreover, the use of antihypertensive medications may
      also confound the relationship between blood pressure and cardiovascular outcome.
      Most important may be the relationship between central blood volume/pressure and
      risk for cardiac events, specifically for congestive heart failure and sudden
      death. Achieving dry-weight during dialysis as opposed to a specific blood
      pressure level is the optimal strategy for reducing cardiovascular events in the
      hemodialysis patient.

PMID- 23127362
TI  - Induction of trans-resveratrol and extracellular pathogenesis-related proteins in
      elicited suspension cultured cells of Vitis vinifera cv Monastrell.
AB  - Suspension-cultured cells of Vitis vinifera cv Monastrell were used to
      investigate the effects of methyljasmonate, ethylene and salicylic acid
      separately or in combination with cyclodextrins on both trans-resveratrol
      production and the induction of defense responses. The results showed that the
      addition of methyljasmonate or ethylene to suspension-cultured cells jointly
      treated with cyclodextrins and salicylic acid provoked a decrease of trans
      resveratrol levels suggesting that salicylic acid has a negative and antagonistic
      effect with methyljasmonate or ethylene on trans-resveratrol production.
      Likewise, the exogenous application of these compounds induced the accumulation
      of pathogenesis-related proteins. Analysis of the extracellular proteome showed
      the presence of amino acid sequences homologous to an specific beta-1,3
      glucanase, class III peroxidases and a beta-1,4-mannanase, which suggests that
      these signal molecules could play a role in mediating defense-related gene
      product expression in V. vinifera cv Monastrell. Apart from these inducible
      proteins, other proteins were found in both the control and elicited cell
      cultures of V. vinifera. These included class IV chitinase, polygalacturonase
      inhibitor protein and reticuline oxidase-like protein, suggesting that their
      expression is constitutive being involved in the modification of the cell wall
      architecture during cell culture growth and in the prevention of pathogen attack.

PMID- 23127363
TI  - Damage and protection of the photosynthetic apparatus from UV-B radiation. I.
      Effect of ascorbate.
AB  - In this work, the effect of the exogenously added ascorbate (Asc) against the UV
      B inhibition of the photosystem II (PSII) functions in isolated pea thylakoid
      membranes was studied. The results reveal that Asc decreases the UV-B induced
      damage of the donor and the acceptor side of PSII during short treatment up to 60
      min. The exogenous Asc exhibits a different UV-protective effect on PSII centers
      in grana and stroma lamellae, as the effect is more pronounced on the PSIIbeta
      centers in comparison to PSIIalpha centers. Data also suggest that one of the
      possible protective roles of the Asc in photosynthetic membranes is the
      modification of the oxygen-evolving complex by influence on the initial S(0)-S(1)
      state distribution in the dark.

PMID- 23127364
TI  - Spinal fusion for chronic low back pain: systematic review on the accuracy of
      tests for patient selection.
AB  - BACKGROUND CONTEXT: Spinal fusion is a common but controversial treatment for
      chronic low back pain (LBP) with outcomes similar to those of programmed
      conservative care. To improve the results of fusion, tests for patient selection
      are used in clinical practice. PURPOSE: To determine the prognostic accuracy of
      tests for patient selection that are currently used in clinical practice to
      identify those patients with chronic LBP who will benefit from spinal fusion.
      STUDY DESIGN: Systematic review of the literature. SAMPLE: Studies that compared
      the results of magnetic resonance imaging (MRI), provocative discography, facet
      joint blocks, orthosis immobilization, and temporary external fixation with the
      clinical outcome of patients who underwent spinal fusion for chronic LBP. OUTCOME
      MEASURES: To determine the prognostic accuracy of tests to predict the clinical
      outcome of spinal fusion in terms of sensitivity, specificity, and likelihood
      ratios (LRs). METHODS: Data sources PubMed (1966 to November 2010), EMBASE (1974
      to November 2010), and reference lists were searched without restriction by
      language or publication status. Two reviewers independently selected studies for
      inclusion, extracted data for analysis, and assessed the risk of bias with the
      Quality Assessment of Diagnostic Accuracy Studies checklist, modified for
      prognostic studies. Discrepancies were resolved by consensus. RESULTS: Ten
      studies met the eligibility criteria. Immobilization by an orthosis (median
      [range] positive LR, 1.10 [0.94-1.13] and negative LR, 0.92 [0.39-1.12]),
      provocative discography (median [range] positive LR, 1.18 [0.70-1.71] and
      negative LR, 0.74 [0.24-1.40]), and temporary external fixation (median [range]
      positive LR, 1.22 [1.02-1.74] and negative LR, 0.58 [0.15-0.94]) failed to show
      clinically useful prognostic accuracy. Statistical pooling was not feasible
      because of different test protocols, variability in outcome assessment, and
      heterogeneous patient populations. No studies reporting on facet joint blocks or
      MRI could satisfy the inclusion criteria. Obscure patient selection, high risk of
      verification bias, and outcome assessment with poorly validated instruments
      precluded strong conclusions for all tests. CONCLUSIONS: No subset of patients
      with chronic LBP could be identified for whom spinal fusion is a predictable and
      effective treatment. Best evidence does not support the use of current tests for
      patient selection in clinical practice.

PMID- 23127365
TI  - Characterization of 8-hydroxyquinoline derivatives containing aminobenzothiazole
      as inhibitors of dengue virus type 2 protease in vitro.
AB  - Four serotypes of dengue virus (DENV1-4), mosquito-borne members of Flaviviridae
      family cause frequent epidemics causing considerable morbidity and mortality in
      humans throughout tropical regions of the world. There is no vaccine or antiviral
      therapeutics available for human use. In a previous study, we reported that
      compounds containing the 8-hydroxyquinoline (8-HQ) scaffold as inhibitors of West
      Nile virus serine protease. In this study, we analyzed potencies of some
      compounds with (8-HQ)-aminobenzothiazole derivatives for inhibition of DENV2
      protease in vitro. We identified analogs 1-4 with 2-aminothiazole or 2
      aminobenzothiazole scaffold with sub-micromolar potencies (IC(50)) in the in
      vitro protease assays. The kinetic constant (K(i)) for the most potent 8-HQ
      aminobenzothiazole inhibitor (compound 1) with an IC(50) value of 0.91+/-0.05MUM
      was determined to be 2.36+/-0.13MUM. This compound inhibits the DENV2 NS2B/NS3pro
      by a competitive mode of inhibition.

PMID- 23127366
TI  - An adenoviral vector-based expression and delivery system for the inhibition of
      wild-type adenovirus replication by artificial microRNAs.
AB  - Human adenoviruses are rarely associated with life-threatening infections in
      healthy individuals. However, immunocompromised patients, and particularly
      allogeneic hematopoietic stem cell transplant recipients, are at high risk of
      developing disseminated and potentially fatal disease. The efficacy of commonly
      used drugs to treat adenovirus infections (i.e., cidofovir in most cases) is
      limited, and alternative treatment options are needed. Artificial microRNAs
      (amiRNAs) are a class of synthetic RNAs resembling cellular miRNAs, and, similar
      to their natural relatives, can mediate the knockdown of endogenous gene
      expression. This process, termed RNA interference, can be harnessed to target and
      potentially silence both cellular and viral genes. In this study, we designed
      amiRNAs directed against adenoviral E1A, DNA polymerase, and preterminal protein
      (pTP) mRNAs in order to inhibit adenoviral replication in vitro. For the
      expression of amiRNA-encoding sequences, we utilized replication-deficient
      adenoviral vectors. In cells transduced with the recombinant vectors and infected
      with the wild-type (wt) adenovirus, one particular amiRNA that was directed
      against the pTP mRNA was capable of decreasing the output of infectious wt virus
      progeny by 2.6 orders of magnitude. This inhibition rate could be achieved by
      concatemerizing amiRNA-encoding sequences to allow for high intracellular amiRNA
      concentrations. Because superinfecting wt virus induces the replication and
      amplification of the recombinant adenoviral vector, amiRNA concentrations were
      increased in cells infected with wt adenovirus. Furthermore, a combination of
      amiRNA expression and treatment of infected cells with cidofovir resulted in
      additive effects that manifested as a total reduction of infectious virus progeny
      by greater than 3 orders of magnitude.

PMID- 23127367
TI  - Systematic review and economic modelling of the relative clinical benefit and
      cost-effectiveness of laparoscopic surgery and robotic surgery for removal of the
      prostate in men with localised prostate cancer.
AB  - BACKGROUND: Complete surgical removal of the prostate, radical prostatectomy, is
      the most frequently used treatment option for men with localised prostate cancer.
      The use of laparoscopic (keyhole) and robot-assisted surgery has improved
      operative safety but the comparative effectiveness and cost-effectiveness of
      these options remains uncertain. OBJECTIVE: This study aimed to determine the
      relative clinical effectiveness and cost-effectiveness of robotic radical
      prostatectomy compared with laparoscopic radical prostatectomy in the treatment
      of localised prostate cancer within the UK NHS. DATA SOURCES: MEDLINE, MEDLINE In
      Process & Other Non-Indexed Citations, EMBASE, BIOSIS, Science Citation Index and
      Cochrane Central Register of Controlled Trials were searched from January 1995
      until October 2010 for primary studies. Conference abstracts from meetings of the
      European, American and British Urological Associations were also searched. Costs
      were obtained from NHS sources and the manufacturer of the robotic system.
      Economic model parameters and distributions not obtained in the systematic review
      were derived from other literature sources and an advisory expert panel. REVIEW
      METHODS: Evidence was considered from randomised controlled trials (RCTs) and non
      randomised comparative studies of men with clinically localised prostate cancer
      (cT1 or cT2); outcome measures included adverse events, cancer related,
      functional, patient driven and descriptors of care. Two reviewers abstracted data
      and assessed the risk of bias of the included studies. For meta-analyses, a
      Bayesian indirect mixed-treatment comparison was used. Cost-effectiveness was
      assessed using a discrete-event simulation model. RESULTS: The searches
      identified 2722 potentially relevant titles and abstracts, from which 914 reports
      were selected for full-text eligibility screening. Of these, data were included
      from 19,064 patients across one RCT and 57 non-randomised comparative studies,
      with very few studies considered at low risk of bias. The results of this study,
      although associated with some uncertainty, demonstrated that the outcomes were
      generally better for robotic than for laparoscopic surgery for major adverse
      events such as blood transfusion and organ injury rates and for rate of failure
      to remove the cancer (positive margin) (odds ratio 0.69; 95% credible interval
      0.51 to 0.96; probability outcome favours robotic prostatectomy = 0.987). The
      predicted probability of a positive margin was 17.6% following robotic
      prostatectomy compared with 23.6% for laparoscopic prostatectomy. Restriction of
      the meta-analysis to studies at low risk of bias did not change the direction of
      effect but did decrease the precision of the effect size. There was no evidence
      of differences in cancer-related, patient-driven or dysfunction outcomes. The
      results of the economic evaluation suggested that when the difference in positive
      margins is equivalent to the estimates in the meta-analysis of all included
      studies, robotic radical prostatectomy was on average associated with an
      incremental cost per quality-adjusted life-year that is less than threshold
      values typically adopted by the NHS (L30,000) and becomes further reduced when
      the surgical capacity is high. LIMITATIONS: The main limitations were the
      quantity and quality of the data available on cancer-related outcomes and
      dysfunction. CONCLUSIONS: This study demonstrated that robotic prostatectomy had
      lower perioperative morbidity and a reduced risk of a positive surgical margin
      compared with laparoscopic prostatectomy although there was considerable
      uncertainty. Robotic prostatectomy will always be more costly to the NHS because
      of the fixed capital and maintenance charges for the robotic system. Our
      modelling showed that this excess cost can be reduced if capital costs of
      equipment are minimised and by maintaining a high case volume for each robotic
      system of at least 100-150 procedures per year. This finding was primarily driven
      by a difference in positive margin rate. There is a need for further research to
      establish how positive margin rates impact on long-term outcomes. FUNDING: The
      National Institute for Health Research Health Technology Assessment programme.

PMID- 23127368
TI  - Developmental changes in children's comprehension and explanation of spatial
      metaphors for time.
AB  - Time is frequently expressed with spatial motion, using one of three different
      metaphor types: moving-time, moving-ego, and sequence-as-position. Previous work
      shows that children can understand and explain moving-time metaphors by age five
      (Ozcaliskan, 2005). In this study, we focus on all three metaphor types for time,
      and ask whether metaphor type has an effect on children's metaphor comprehension
      and explanation abilities. Analysis of the responses of three- to six-year-old
      children and adults showed that comprehension and explanation of all three
      metaphor types emerge at an early age. Moreover, children's metaphor
      comprehension and explanation vary by metaphor type: children perform better in
      understanding and explaining metaphors that structure time in relation to the
      observer of time (moving-ego, moving-time) than metaphors that structure time
      without any relation to the observer of time (sequence-as-position-on-a-path).
      Our findings suggest that children's bodily experiences might play a role in
      their developing understanding of the abstract concept of time.

PMID- 23127369
TI  - Early outcome of folding mitral valve repair technique without resection for
      mitral valve prolapse in 60 patients.
AB  - OBJECTIVES: Leaflet resection represents the reference standard for mitral valve
      regurgitation. However, the resection technique is irreversible and requires
      leaflet cutting and reapproximation. Folding mitral valve repair is a
      nonresectional technique with inversion of the prolapsed segment into the left
      ventricle. The present study evaluated the effectiveness of this technique.
      METHODS: The prolapsed segment was inverted into the left ventricle vertically. A
      pilot suture was placed at the free edge of the leaflet. After confirming no
      mitral valve regurgitation with a pressure test, additional sutures were placed
      toward the annulus. If the test still showed mitral valve regurgitation, the
      suture was removed and repositioned. Ring annuloplasty was performed in all
      patients, except those with active infectious endocarditis. The repaired mitral
      valve was evaluated using echocardiography. RESULTS: A total of 60 patients (37
      men; mean age, 62.4 years) underwent folding mitral valve repair from January
      2007 to September 2011. Of these patients, 38 (63%) had moderate and 18 (30%) had
      severe mitral valve regurgitation preoperatively. Folding mitral valve repair was
      applied to the anterior leaflet and posterior leaflet. The mean cardiopulmonary
      bypass time and crossclamp time were 148 and 90 minutes, respectively. No patient
      had systolic anterior motion. Postoperative echocardiography revealed no mitral
      valve regurgitation to trivial mitral valve regurgitation in 48 and mild mitral
      valve regurgitation in 12 patients. No patient required reoperation for recurrent
      mitral valve regurgitation. CONCLUSIONS: Folding mitral valve repair is an easily
      fine-tuned technique with a pilot suture, which can be easily removed and
      repositioned, if unsatisfactory. This reversibility is a significant advantage of
      this technique. Long-term follow-up is necessary to assess the durability of this
      technique.

PMID- 23127371
TI  - Patterns of recurrence and second primary lung cancer in early-stage lung cancer
      survivors followed with routine computed tomography surveillance.
AB  - OBJECTIVE: At present, there is no consensus on the optimal strategy for follow
      up care after curative resection for lung cancer. We sought to understand the
      patterns of recurrence and second primary lung cancer, and their mode of
      detection, after resection for early-stage non-small cell lung cancer in patients
      who were followed by routine surveillance computed tomography scan. METHODS: We
      reviewed the outcomes of consecutive patients who underwent resection for early
      stage non-small cell lung cancer at Memorial Sloan-Kettering Cancer Center
      between 2004 and 2009. RESULTS: A total of 1294 consecutive patients with early
      stage non-small cell lung cancer underwent resection. The median length of follow
      up was 35 months. Recurrence was diagnosed in 257 patients (20%), and second
      primary lung cancer was diagnosed in 91 patients (7%). The majority of new
      primary cancers (85 [93%]) were identified by scheduled routine computed
      tomography scan, as were a smaller majority of recurrences (157 [61%]). During
      the first 4 years after surgery, the risk of recurrence ranged from 6% to 10% per
      person-year but decreased thereafter to 2%. Conversely, the risk of second
      primary lung cancer ranged from 3% to 6% per person-year and did not diminish
      over time. Additional testing after false-positive surveillance computed
      tomography scan results was performed for 329 patients (25%), but only 4 of these
      patients (0.3%) experienced complications as a result of subsequent invasive
      diagnostic procedures. CONCLUSIONS: Almost all second primary cancers and the
      majority of recurrences were detected by post-therapeutic surveillance computed
      tomography scan. The risk of recurrence for early-stage non-small cell lung
      cancer survivors persisted during the first 4 years after resection, and
      vigilance in surveillance should be maintained.

PMID- 23127374
TI  - Effect of cytokine hemoadsorption on brain death-induced ventricular dysfunction
      in a porcine model.
AB  - OBJECTIVE: In an effort to expand the cardiac donor pool, we tested the
      hypothesis that hemoadsorption of cytokines attenuates brain death-induced
      ventricular dysfunction. METHODS: Eighteen Yorkshire pigs (50-60 kg) were
      instrumented with a left ventricular conductance catheter. Cytokine expression,
      preload recruitable stroke work, and the diastolic relaxation constant tau were
      measured at baseline and at hourly intervals for 6 hours after induction of brain
      death by intracranial balloon inflation (brain death, n = 6) or sham operation
      (control, n = 6). In a third group (brain death + hemoadsorption, n = 6), 3 hours
      after induction of brain death, animals were placed on an extracorporeal circuit
      containing a cytokine-hemoadsorption device for the remaining 3 hours of the
      experiment. Myocardial water content was measured after the animals were killed.
      RESULTS: Six hours after induction of brain death, tumor necrosis factor and
      interleukin-6 were highest in the brain death group (106 +/- 13.1 pg/mL and 301
      +/- 181 pg/mL, respectively), lowest in controls (68.3 +/- 8.55 pg/mL and 37.8 +/
      11 pg/mL, respectively), and intermediate in the brain death + hemoadsorption
      group (81.2 +/- 35.2 pg/mL and 94.6 +/- 20 pg/mL, respectively). Compared with
      controls, preload recruitable stroke work was significantly reduced in the brain
      death group 4 hours after the induction of brain death and was 50% of baseline by
      5 hours. In the brain death + hemoadsorption group, preload recruitable stroke
      work was relatively preserved at 80% of baseline at similar time points. Tau
      remained unchanged in the control and brain death + hemoadsorption groups,
      whereas in the brain death group it was significantly elevated versus baseline 5
      (139.3% +/- 21.5%) and 6 (172% +/- 16.1%) hours after induction of brain death.
      Myocardial water content was significantly greater in the brain death group than
      in the other 2 groups. CONCLUSIONS: Hemoadsorption of cytokines using an
      extracorporeal circuit attenuates brain death-induced ventricular dysfunction in
      a porcine model. Improvement in function generally correlates with trends in
      cytokine expression, but this relationship requires further investigation.

PMID- 23127376
TI  - Mitral valve repair or replacement for ischemic mitral regurgitation? The Italian
      Study on the Treatment of Ischemic Mitral Regurgitation (ISTIMIR).
AB  - OBJECTIVE: It is uncertain whether mitral valve replacement is really inferior to
      mitral valve repair for the treatment of chronic ischemic mitral regurgitation.
      This multicenter study aimed at providing a contribution to this issue. METHODS:
      Of 1006 patients with chronic ischemic mitral regurgitation and impaired left
      ventricular function (ejection fraction < 40%) operated on at 13 Italian
      institutions between 1996 and 2011, 298 (29.6%) underwent mitral valve
      replacement whereas 708 (70.4%) received mitral valve repair. Propensity scores
      were calculated by a nonparsimonious multivariable logistic regression, and 244
      pairs of patients were matched successfully using calipers of width 0.2 standard
      deviation of the logit of the propensity scores. The postmatching median
      standardized difference was 0.024 (range, 0-0.037) and in none of the covariates
      did it exceed 10%. RESULTS: Early deaths were 3.3% (n = 8) in mitral valve repair
      versus 5.3% (n = 13) in mitral valve replacement (P = .32). Eight-year survival
      was 81.6% +/- 2.8% and 79.6% +/- 4.8% (P = .42), respectively. Actual freedom
      from all-cause reoperation and valve-related reoperation were 64.3% +/- 4.3%
      versus 80% +/- 4.1%, and 71.3% +/- 3.5% versus 85.5% +/- 3.9 in mitral valve
      repair and mitral valve replacement, respectively (P < .001). Actual freedom from
      all valve-related complications was 68.3% +/- 3.1% versus 69.9% +/- 3.3% in
      mitral valve repair and mitral valve replacement, respectively (P = .78). Left
      ventricular function did not improved significantly, and it was comparable in the
      2 groups postoperatively (36.9% vs 38.5%, P = .66). At competing regression
      analysis, mitral valve repair was a strong predictor of reoperation (hazard
      ratio, 2.84; P < .001). CONCLUSIONS: Mitral valve replacement is a suitable
      option for patients with chronic ischemic mitral regurgitation and impaired left
      ventricular function. It provides better results in terms of freedom from
      reoperation with comparable valve-related complication rates.

PMID- 23127377
TI  - Diverging effects of clean versus dirty money on attitudes, values, and
      interpersonal behavior.
AB  - Does the cue of money lead to selfish, greedy, exploitative behaviors or to
      fairness, exchange, and reciprocity? We found evidence for both, suggesting that
      people have both sets of meaningful associations, which can be differentially
      activated by exposure to clean versus dirty money. In a field experiment at a
      farmers' market, vendors who handled dirty money subsequently cheated customers,
      whereas those who handled clean money gave fair value (Experiment 1). In
      laboratory studies with economic games, participants who had previously handled
      and counted dirty money tended toward selfish, unfair practices-unlike those who
      had counted clean money or dirty paper, both of which led to fairness and
      reciprocity. These patterns were found with the trust game (Experiment 2), the
      prisoner's dilemma (Experiment 4), the ultimatum game (Experiment 5), and the
      dictator game (Experiment 6). Cognitive measures indicated that exposure to dirty
      money lowered moral standards (Experiment 3) and reduced positive attitudes
      toward fairness and reciprocity (Experiments 6-7), whereas exposure to clean
      money had the opposite effects. Thus, people apparently have 2 contradictory sets
      of associations (including behavioral tendencies) to money, which is a complex,
      powerful, and ubiquitous aspect of human social life and cultural organization.

PMID- 23127378
TI  - Next-generation negative symptom assessment for clinical trials: validation of
      the Brief Negative Symptom Scale.
AB  - The current study examined the psychometric properties of the Brief Negative
      Symptom Scale (BNSS), a next-generation rating instrument developed in response
      to the NIMH sponsored consensus development conference on negative symptoms.
      Participants included 100 individuals with a DSM-IV diagnosis of schizophrenia or
      schizoaffective disorder who completed a clinical interview designed to assess
      negative, positive, disorganized, and general psychiatric symptoms, as well as
      functional outcome. A battery of anhedonia questionnaires and neuropsychological
      tests were also administered. Results indicated that the BNSS has excellent
      internal consistency and temporal stability, as well as good convergent and
      discriminant validity in its relationships with other symptom rating scales,
      functional outcome, self-reported anhedonia, and neuropsychological test scores.
      Given its brevity (13-items, 15-minute interview) and good psychometric
      characteristics, the BNSS can be considered a promising new instrument for use in
      clinical trials.

PMID- 23127379
TI  - Characteristics of suicide attempts in patients diagnosed with schizophrenia in
      comparison with depression: a study of emergency room visit cases in Japan.
AB  - We worked on characterizing suicide attempts in patients with schizophrenia in
      comparison with mood disorders. This study population comprised 260 patients with
      F2 disorders (ICD-10), i.e., "schizophrenic group" and 705 patients with F3
      disorders, i.e., "depressive group" who presented at the psychiatric emergency
      department of our hospital for 8 years. They were compared in three age groups:
      young (<=24 years), middle-aged (25-44 years), and elderly (>=45 years).
      Multivariate logistic regression analysis identified factors associated with the
      seriousness of the suicide attempt method. The schizophrenic group (>=25 years)
      had a younger mean age and higher prevalences of "within-1-year suicide attempts"
      and "past suicide attempts" than the depressive group. The Schizophrenic group
      tended to use serious methods, such as "jumping from high places," "throwing
      oneself in front of an oncoming train," and "burning oneself," in their suicide
      attempts, with "hallucination-delusion" accounting for an overwhelmingly large
      percentage of suicide attempt motives, irrespective of the age group. In the
      elderly group, the ratio of "no-housemate" patients was high. In all age groups,
      jobless individuals were prevalent, and the schizophrenic group had lower LCU
      (Life Change Unit) scores than did the depressive group. The middle-aged cases of
      schizophrenic group had higher BPRS (Brief Psychiatric Rating Scale) scores and
      lower GAS (Global Assessment Scale) scores. Regarding factors influencing the
      seriousness of the methods, a history of within-1-year suicide attempts increased
      the method seriousness in the schizophrenic group. Years of education correlated
      with the method seriousness in the schizophrenic group. Low scores of overall
      health on the GAS increased the method seriousness in both groups.

PMID- 23127380
TI  - Executive functioning during full and partial remission (positive and negative
      symptomatic remission) of schizophrenia.
AB  - BACKGROUND: Despite the upsurge of research regarding cognitive impairment in
      schizophrenia we still lack adequate understanding of the executive functioning
      of patients in symptomatic remission. Moreover, the cognitive functioning of
      patients in partial remission has not been studied previously although they
      comprise a significant proportion of schizophrenia patients. The current study
      therefore examined the executive functioning of patients in full symptomatic
      remission and for the first time assessed two sub-groups of patients in partial
      remission. METHODS: Executive functioning of five groups was compared;
      symptomatic patients, patients in positive symptomatic remission, negative
      symptomatic remission, full symptomatic remission (SP, PSR, NSR, and FSR; N=101)
      and healthy controls (N=37). RESULTS: A graded cognitive profile was evident
      between the groups. SP patients exhibited widespread executive dysfunction while
      the performance of FSR patients was comparable to that of the healthy controls.
      Both PSR and NSR patients had working memory deficits, with PSR patients showing
      additional deficits in cognitive planning. CONCLUSIONS: The findings are
      encouraging, tentatively suggesting intact executive functioning among patients
      in full symptomatic remission. The graded cognitive profile of the patient groups
      strengthens earlier findings indicating the significant role of negative symptoms
      in determining executive dysfunction in schizophrenia. The findings point toward
      potential targets for therapeutic efforts and emphasize the need for further
      research of sub-groups of schizophrenia patients in partial remission.

PMID- 23127381
TI  - Integrative mobile elements exploiting Xer recombination.
AB  - Integrative mobile genetic elements directly participate in the rapid response of
      bacteria to environmental challenges. They generally encode their own dedicated
      recombination machineries. CTXphi, a filamentous bacteriophage that harbors the
      genes encoding cholera toxin in Vibrio cholerae provided the first notable
      exception to this rule: it hijacks XerC and XerD, two chromosome-encoded tyrosine
      recombinases for lysogenic conversion. XerC and XerD are highly conserved in
      bacteria because of their role in the topological maintenance of circular
      chromosomes and, with the advent of high throughput sequencing, numerous other
      integrative mobile elements exploiting them have been discovered. Here, we review
      our understanding of the molecular mechanisms of integration of the different
      integrative mobile elements exploiting Xer (IMEXs) so far described.

PMID- 23127382
TI  - The use of the urogenital papillae of male feral African sharptooth catfish
      (Clarias gariepinus) as indicator of exposure to estrogenic chemicals in two
      polluted dams in an urban nature reserve, Gauteng, South Africa.
AB  - The African sharptooth catfish (Clarias gariepinus) is indigenous to South Africa
      where it is commonly found in calm waters such as lakes, streams, rivers, swamps
      and floodplains. The males of this gonochoristic species can be readily
      distinguished from females via a distinct elongated urogenital papilla with a
      pointed tip, located just behind the anus. This structure is an androgen
      controlled secondary sexual characteristic and could potentially be affected by
      chemicals displaying endocrine disrupting properties during development. Results
      of previous studies on effects on papillae of different fish species indicated
      that these structures could be useful as bio-indicators of exposure due to
      alterations in the structures. This study investigated the occurrence of abnormal
      morphology in urogenital papillae compared to the macroscopic and microscopic
      structure of the gonads of presumed male or intersex catfish sampled from the
      Rietvlei and Marais dams in an urban nature reserve, due to exposure to endocrine
      disrupting chemicals (EDCs). Macroscopic observation of the UGP, gonad
      examination after laparotomy and histology were done. Gonadosomatic index (GSI)
      and Urogenital papilla length index (UGPLI) were determined for all fish
      collected. Mesenteric fat analyzed for selected alkylphenols and organochlorines
      showed high levels of especially nonylphenol indicating long term exposure to
      these chemicals due to bio-accumulation. The GSI indicated that fish with
      intersex gonads were probably feminized males. It was concluded that use of the
      UGP alone, without macroscopic and microscopic analyses of the gonads, could not
      effectively indicate exposure to EDCs.

PMID- 23127383
TI  - Evaluation of white blood cell count in peritoneal fluid with five different
      hemocytometers.
AB  - OBJECTIVES: Evaluation of automated flow cytometric analysis of white blood cell
      (WBC) count in peritoneal fluids. METHODS: One hundred peritoneal fluids were
      analyzed with manual microscopy, Sysmex XE-2100 and XE-5000, Siemens Advia 2120,
      Mindray BC-6800, Abbott Sapphire. RESULTS: High correlations (0.978 to 0.999) and
      modes biases (-132 to 80 WBC/mm(3)) were found. Agreement at septic peritonitis
      cutoff ranged between 96% and 99%. CONCLUSIONS: These hemocytometers display
      acceptable performance for WBC screening in peritoneal fluids.

PMID- 23127384
TI  - Highly sensitive measurement of whole blood chromium by inductively coupled
      plasma mass spectrometry.
AB  - OBJECTIVES: Chromium (Cr), a trace metal element, is implicated in diabetes and
      cardiovascular disease. A hypochromic state has been associated with poor blood
      glucose control and unfavorable lipid metabolism. Sensitive and accurate
      measurement of blood chromium is very important to assess the chromium
      nutritional status. However, interferents in biological matrices and
      contamination make the sensitive analysis challenging. The primary goal of this
      study was to develop a highly sensitive method for quantification of total Cr in
      whole blood by inductively coupled plasma mass spectrometry (ICP-MS) and to
      validate the reference interval in a local healthy population. DESIGN AND
      METHODS: This method was developed on an ICP-MS with a collision/reaction cell.
      Interference was minimized using both kinetic energy discrimination between the
      quadrupole and hexapole and a selective collision gas (helium). Reference
      interval was validated in whole blood samples (n=51) collected in trace element
      free EDTA tubes from healthy adults (12 males, 39 females), aged 19-64 years
      (38.8+/-12.6), after a minimum of 8 h fasting. Blood samples were aliquoted into
      cryogenic vials and stored at -70  degrees C until analysis. RESULTS: The assay
      linearity was 3.42 to 1446.59 nmol/L with an accuracy of 87.7 to 99.8%. The high
      sensitivity was achieved by minimization of interference through selective
      kinetic energy discrimination and selective collision using helium. The reference
      interval for total Cr using a non-parametric method was verified to be 3.92 to
      7.48 nmol/L. CONCLUSION: This validated ICP-MS methodology is highly sensitive
      and selective for measuring total Cr in whole blood.

PMID- 23127385
TI  - Evaluation of digital images for identification and characterization of
      monoclonal immunoglobulins by immunofixation.
AB  - OBJECTIVES: High resolution digital imaging systems were recently introduced to
      capture and visualize serum protein electrophoresis results. In this study, we
      compared the performance of five, experienced interpreters using digital images
      and physical gels to identify and characterize monoclonal gammopathies by
      immunofixation. DESIGN AND METHODS: Immunofixation gels were generated using
      Sebia's HYDRASYS and digital images were captured with Sebia's Gelscan system.
      Interpreters blindly reviewed 200 consecutively obtained immunofixation results
      using physical gels, low resolution (LR) images, and high resolution (HR) images.
      RESULTS: Interpretations of the physical gels were significantly more sensitive
      (p<=0.01) than LR and HR images, and significantly more specific (p<0.001) than
      the LR images. Interpreters had a sensitivity of 82.0% (45.8-95.7) using the LR
      images and a specificity of 71.0% (47.8-91.3); using the HR images interpreters
      had a sensitivity of 80.4% (68.1-86.8) and specificity of 91.8% (80.3-97.8).
      There was 73.6% agreement between the HR digital images and the physical gel for
      immunoglobulin isotype characterization. Interpreters using digital images
      collectively missed 19 patients with monoclonal immunoglobulins that were
      identified using physical gels. CONCLUSIONS: Interpreters using digital images
      had significantly different performance than when using physical agarose gels.
      Differences were most pronounced for low concentration monoclonal gammopathies
      (<0.3 g/dL) and for complex patterns. Between-interpreter agreement was also
      lower using digital images. While digital images may serve as a useful resource
      for retrospective analysis and review of previous results, they are not
      equivalent to physical gels. Additional studies are warranted to explore the
      clinical impact of these observed differences.

PMID- 23127386
TI  - Third universal definition of myocardial infarction.

PMID- 23127387
TI  - Long-term functional benefits of epicardial patches as cell carriers.
AB  - Both enzymatic dissociation of cells prior to needle-based injections and poor
      vascularization of myocardial infarct areas are two important contributors to
      cell death and impede the efficacy of cardiac cell therapy. Because these
      limitations could be overcome by scaffolds ensuring cell cohesiveness and
      codelivery of angiogenic cells, we used a chronic rat model of myocardial
      infarction to assess the long-term (6 months) effects of the epicardial delivery
      of a composite collagen-based patch harboring both cardiomyogenesis-targeted
      human embryonic SSEA-1(+) (stem cell-derived stage-specific embryonic antigen-1
      positive) cardiovascular progenitors and autologous (rat) adipose tissue-derived
      angiogenesis-targeted stromal cells (n = 27). Cell-free patches served as
      controls (n = 28). Serial follow-up echocardiographic measurements of left
      ventricular ejection fraction (LVEF) showed that the composite patch group
      yielded a significantly better preservation of left ventricular function that was
      sustained over time as compared with controls, and this pattern persisted when
      the assessment was restricted to the subgroup of rats with initial LVEFs below
      50%. The composite patch group was also associated with significantly less
      fibrosis and more vessels in the infarct area. However, although human
      progenitors expressing cardiac markers were present in the patches before
      implantation, none of them could be subsequently identified in the grafted
      tissue. These data confirm the efficacy of epicardial scaffolds as cell carriers
      for ensuring long-term functional benefits and suggest that these effects are
      likely related to paracrine effects and call for optimizing cross-talks between
      codelivered cell populations to achieve the ultimate goal of myocardial
      regeneration. 

PMID- 23127388
TI  - Phage-display and related areas.

PMID- 23127389
TI  - Microtubule-based transport in filamentous fungi.
AB  - Defects in microtubule-based transport are implicated in many neuropathologies.
      The filamentous fungi Aspergillus nidulans and Ustilago maydis are valuable
      models for studying transport owing to their yeast-like genetic and biochemical
      tractability and metazoan-like dependence on microtubule-based transport for
      cellular trafficking. In these organisms the role of microtubules in nuclear
      positioning is well studied, but recent work has expanded the range of cargos to
      include endosomes, messenger RNA, secretory vesicles, peroxisomes, and nuclear
      pore complexes, reflecting the diversity of metazoan systems. Furthermore,
      similarities in transport mechanisms exist between filamentous fungi and metazoan
      neurons, demonstrating the suitability of A. nidulans and U. maydis for studying
      the molecular basis of transport-related neuropathologies such as lissencephaly,
      motor neuron disease, and Perry syndrome.

PMID- 23127390
TI  - Computed tomography-based sizing recommendations for transcatheter aortic valve
      replacement with balloon-expandable valves: Comparison with transesophageal
      echocardiography and rationale for implementation in a prospective trial.
AB  - BACKGROUND: Computed tomography (CT) annular measurements are predictive of
      paravalvular regurgitation after transcatheter aortic valve replacement (TAVR)
      which is a predictor of mortality and morbidity. OBJECTIVES: To demonstrate the
      rationale and potential implications of new CT sizing recommendations for TAVR.
      METHODS: The CT sizing recommendations aim to ensure routine transcatheter heart
      valve (THV) oversizing of the aortic annular area [(THV external area/systolic
      annular area - 1) * 100; range, 1%-20%; target, 10%-15%]. Consecutive patients (n
      = 120) underwent CT before TAVR with balloon-expandable valves sized by
      transesophageal echocardiography (TEE). Retrospectively, the CT-recommended THV
      size was compared with the actual size implanted. RESULTS: Compared with TEE,
      application of the newly developed CT-based sizing recommendations would have led
      to implantation of a larger valve in 33.3% (40/120), no change in valve size in
      55.8% (67/120), and a smaller valve in 10.8% (13/120). In patients when CT
      recommended a larger valve, the incidence of at least moderate paravalvular
      regurgitation was 25% (10/40) compared with 4.5% (3/67; P < 0.01) when both TEE
      and CT recommendations were in agreement. Using diastolic versus systolic CT
      measurements results in 20% of patients receiving smaller THVs. TEE sizing
      resulted in 33.3% (40/120) of valves being undersized (THV area < CT systolic
      annular area) with a mean annular oversizing of 9.4% +/- 17.4% (range: -21.5% to
      65.9%) without annular rupture. In contrast, the CT sizing recommendations
      results in mean annular oversizing of 13.9% +/- 8.0% (range, 1.3%-29.8%).
      CONCLUSION: These CT sizing recommendations enable standardized moderate
      overexpansion of the aortic annulus. Clinical outcomes from these recommendations
      are being prospectively assessed in a multicenter trial.

PMID- 23127391
TI  - Cardiac CT training: we need to improve?

PMID- 23127392
TI  - The current and future roles of community pharmacists: views and experiences of
      patients with type 2 diabetes.
AB  - BACKGROUND: The current UK government agenda is for community pharmacists to
      assume greater responsibility for medication management in patients with chronic
      conditions. This agenda may require a significant change in the way patients
      currently interact with their community pharmacist. OBJECTIVES: To explore the
      experiences and views of patients with type 2 diabetes regarding the current and
      proposed future role of community pharmacists. METHODS: This study used focus
      groups to collect experiences and views of patients with type 2 diabetes. A
      National Health Service (NHS) ethics committee approved this study. Pharmacists
      identified all patients with type 2 diabetes to whom they provided an information
      sheet and a consent form which included a request to supply basic demographic
      details. Focus group members were purposively sampled to gain a diverse range of
      opinions. Two researchers independently coded and thematically analyzed the
      transcripts. The researchers discussed the emergent themes to ensure all valid
      themes had been identified. RESULTS: Twenty-five participants attended one of 4
      focus groups. Two broad themes were identified: the place of pharmacy in the
      wider primary care team and pharmacy as a healthcare destination. Participants
      who had been living with diabetes for a long time and those who felt they had
      received a lower level of care from the medical practice were more likely to
      acknowledge contributions of pharmacists in their care for advice on side
      effects, drug interactions and supply than participants with a good relationship
      with their general practitioner (GP) or practice nurse and whose diabetes was
      well controlled. CONCLUSIONS: Participants with type 2 diabetes identified a role
      for pharmacists in their care linked to their perceived expertise on medicines.
      However, the extent to which they would engage with the pharmacist depended on
      the quality of relationship with their GP or practice nurse.

PMID- 23127393
TI  - [MRI in congenital Brown's syndrome: report of 16 cases].
AB  - INTRODUCTION: Superior oblique retraction syndrome or Brown's syndrome is one of
      the so-called restrictive syndromes causing anatomic strabismus. It is
      characterized by active and passive limitation of upward gaze in adduction in the
      field of action of the superior oblique muscle (SO). The etiology of this
      congenital syndrome remains unknown. The purpose of this prospective study is to
      analyze brain and orbital magnetic resonance imaging (MRI) in patients with
      congenital Brown's syndrome. PATIENTS AND METHODS: Sixteen children (19 months -
      9 years) underwent complete ophthalmologic evaluation followed by brain/orbital
      MRI with attention to the superior oblique muscle. Average age at time of MRI was
      4.2 years old. Among patients included were eight girls and eight boys. MRI was
      performed on a 1.5T (Symphony TIM, Siemens, Erlangen) to visualize the orbit and
      specifically the SO. RESULTS: Of 16 eyes, 13 demonstrated radiologic
      abnormalities of the SO muscle; six demonstrated tendon-trochlea complex
      hypertrophy, four demonstrated complete SO hypertrophy (tendon-trochlea-muscle
      belly), one demonstrated trochlear hypertrophy, and two demonstrated
      abnormalities solely of the tendons, of which one was longer and one was thinner
      with fibrosis. CONCLUSION: MRI shows a high frequency of SO radiologic
      abnormalities in congenital Brown's syndrome. MRI permits the analysis of not
      only the tendon, but also the trochlea and muscle belly, whereas surgery only
      allows visualization of the tendon. MRI proved to be an interesting tool for
      investigation of these patients and for a better understanding of the
      pathogenesis.

PMID- 23127394
TI  - Achieving high throughput sequencing of a cDNA library utilizing an alternative
      protocol for the bench top next-generation sequencing system.
AB  - The development of next-generation sequencing (NGS) technologies has provided
      novel tools for genome analysis and expression profiling. A high throughput cDNA
      sequencing method using a bench top next-generation sequencing system, GS Junior,
      is now available. Here, we used an alternative protocol to the standard method
      for generating the cDNA library. This protocol can decrease the number of
      processing steps to manipulate RNA when constructing a cDNA library from an RNA
      sample, and does not require mRNA isolation from total RNA. Thus it can decrease
      the risk of RNA degradation and the cost for preparing a cDNA library. Also, the
      efficiency of sequencing data obtained with this approach is comparable to the
      standard method as verified by sequencing characteristics and expression levels
      of the reference gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH).

PMID- 23127395
TI  - A Shiga toxin-producing Escherichia coli O157 outbreak associated with
      consumption of rice cakes in 2011 in Japan.
AB  - In May 2011, an outbreak of Shiga toxin-producing Escherichia coli (STEC) O157
      was reported from Yamagata Prefecture, Japan. Investigations, including a case
      control study, revealed that the outbreak was linked to two varieties of rice
      cakes produced by a local manufacturer between 2 and 7 May. Active and passive
      surveillance identified 136 suspected cases, 142 confirmed cases, 26 asymptomatic
      cases, and 25 secondary cases. While no environmental samples taken from the
      manufacturing premises tested positive for STEC, other than a stool sample taken
      from one employee, on-site and epidemiological investigations indicated that STEC
      was introduced during the manufacturing process of rice cakes rather than through
      contamination of raw materials. This was the first reported outbreak of STEC
      associated with cakes and confectionery in Japan, which indicates that
      contamination and outbreaks of STEC can occur in any food unless proper
      precautions are taken.

PMID- 23127396
TI  - [Inhibitory effects of HIV-1 gp41 fusion peptide on CD3 antibody activated 
      regulatory T cells].
AB  - AIM: To investigate whether the HIV-1 gp41 fusion peptide (FP) could affect the
      regulatory T cell (Treg) function activated by CD3 antibody. METHODS: Murine
      CD4(+);CD25(+); Treg and CD4(+);CD25(-); effector T cells (Teff) were isolated
      from mice spleens by the immune magnetic beads. The splenocytes were treated with
      mitomycin C to obtain antigen presenting cells (APCs). CCK-8 assay and CFSE
      loading were employed to evaluate the effects of FP on the Treg inhibitory
      function via measuring Teff proliferation activated by CD3 antibody. In addition,
      IL-10 secretion of activated Treg was detected by ELISA. The distribution of FP
      and TCR on Treg surface was observed by laser scanning confocal microscope.
      RESULTS: Through the CCK-8 assay and flow cytometry, we found that Teff cells
      have significant proliferation stimulated by the CD3 antibodies. When Treg and
      Teff were co-cultured, the proliferation of Teff was significantly inhibited by
      Treg. When added with 25 MUg/mL FP, the proliferation of Treg+Teff group and Teff
      group was not significantly affected, but when 5 MUg/mL FP was added, the
      proliferation rate of Treg+Teff group was significantly lower than that of Teff
      group. IL-10 secretion was low when Treg were not activated, but it significantly
      increased by CD3 antibodies stimulation. When the concentration of FP was 25
      MUg/mL, IL-10 level significantly decreased, but 5 MUg/mL FP did not
      significantly influence IL-10 secretion. Through the laser scanning confocal
      microscope, we found that T cell receptors (TCR) of non-activated Treg showed
      uniform distribution on the cell surface, and that FP and TCR had no common
      distribution. When Treg were stimulated by CD3 antibodies, the activated TCR
      formed half crescent, and FP and the activated TCR had common distribution on
      cell surface. CONCLUSION: Treg inhibitory function is significantly inhibited by
      25 MUg/mL FP in vitro, but 5 MUg/mL FP does not affect it. This may be due to the
      suppression of IL-10 secretion and the influence of the signaling cross-talk
      between APC and TCR.

PMID- 23127397
TI  - [Roles of Th17 lymphocytes and  inflammatory cytokines in airway inflammation
      exacerbation of murine asthmatic model].
AB  - AIM: To investigate the roles of Th17 lymphocytes and its inflammatory cytokines
      in airway inflammation exacerbation of murine asthmatic model. METHODS: Twenty
      mice were randomized into control group and asthma group. For the murine asthma
      model,  the mice were sensitized and challenged with ovalbumin (OVA). The control
      mice were given normal  saline alone under the same conditions as the asthma
      group. We observed the changes in cellular proportions in the bronchoalveolar
      lavage fluid (BALF) under a light microscope and the histological changes in lung
      tissue by HE staining. The levels of IL-4,  IFN-gamma and IL-17 were detected by
      ELISA. Th1,  Th2 and Th17 cells in the peripheral blood were detected by flow
      cytometry. We did a correlation analysis between Th1,  Th2 and Th17 cells in the
      peripheral blood and neutrophils in BALF. RESULTS: The total cell number and the
      percentages of neutrophils,  eosinophils and lymphocytes in BALF of the asthmatic
      mice were significantly higher than those in the control mice (P<0.05). The
      neutrophils and eosinophils infiltration in pulmonary tissue was also
      dramatically detected in asthmatic mice. The levels of IL-4 and IL-17 were
      significantly higher than those in the control mice (P<0.05),  while the level of
      IFN-gamma was much lower than in the control mice (P<0.05). Besides,  the
      percentages of Th2 and Th17 cells in peripheral blood were significantly higher
      in the asthmatic mice than in the control mice (P<0.05). The expression of Th17
      was positively correlated with the levels of neutrophils in BALF(r(Th17);=0.394, 
      P<0.05),  and the expression of Th1 was negatively correlated with the level of
      neutrophils in BALF (r(Th1);=-0.446,  P<0.05). CONCLUSION: Th17 cells could
      induce the recruitment of inflammatory cytokines and neutrophils into airways, 
      which might aggravate the asthmatic inflammation and be related with asthma
      exacerbation.

PMID- 23127398
TI  - [Effect of tyrosine kinase inhibitor imatinib mesylate   on K562 cell invasion by
      PTEN pathway].
AB  - AIM: To investigate the effect of tyrosine kinase inhibitor imatinib mesylate on
      the PTEN signaling pathway and the cell invasion in K562 cells. METHODS: K562
      cells were treated with different concentrations of imatinib mesylate. After
      different time periods,  the mRNA levels of BCR/ABL,  PTEN and FAK were detected
      by real-time fluorescent quantitative PCR (FQ-PCR) to analyze their
      relationships. The protein level of FAK was detected by immunocytochemistry. The
      cell invasive ability was examined by Transwell (Boyden chamber)  assay. RESULTS:
      In the initial 36 h,  the expression level of PTEN mRNA was up-regulated and the
      FAK mRNA was down-regulated with the reduction of BCR/ABL fusion gene expression
      and the cell invasive ability of K562 cells was inhibited by 2 MUg/mL imatinib
      mesylate. 48 h later,  the PTEN mRNA expression level decreased and the FAK mRNA
      expression level was elevated with the restore of BCR/ABL fusion gene. BCR/ABL
      mRNA level presented a positive correlation with PTEN mRNA expression level,  and
      a negative correlation with FAK mRNA. CONCLUSION: Tyrosine kinase inhibitor
      imatinib mesylate can regulate PTEN/FAK pathway and inhibit the leukemia K562
      cell invasive ability via restraining BCR/ABL fusion gene.

PMID- 23127399
TI  - [Xinfeng Capsule improves cardiopulmonary function of knee osteoarthritis rats by
      BTLA-HVEM signaling pathway to induce Treg immune tolerance].
AB  - AIM: To observe the effects of Xinfeng Capsule (XFC) on cardiopulmonary function
      of knee osteoarthritis (KOA) rats and explore its molecular mechanism. METHODS:
      Forty rats were randomly divided into normal control (NC) group, model control
      (MC) group, glucosamine control (GS) group and XFC group, 10 in each group. All
      rats were induced to KOA by injected papain and L-Cys into the right knee joint
      except NC group. Fourteen days after modeling, NC and MC groups were given normal
      saline (0.01 g/kg), GS and XFC groups were given glucosamine (0.098 g/kg) and
      XFC suspension (0.375 g/kg), respectively. Cardiac and pulmonary function were
      detected by ultrasonography and animal spirometry, respectively. B and T
      lymphocyte attenuator (BTLA), herpesvirus entry mediator (HVEM), interleukin (IL)
      17, IL-4, transforming growth factor-beta (TGF-beta1) were detected by ELISA;
      CD4(+);CD25(+);Treg and CD4(+); CD25(+);Foxp3(+); Treg were detected by flow
      cytometry. RESULTS: Compared with NC group, body mass, levels of early diastolic
      peak flow velocity (E), early diastolic peak flow velocity/atrial peak flow
      velocity (E/A), forced vital capacity (FVC), forced expiratory volume in 1 second
      (FEV1), 25% forced expiratory flow (FEF25), 50% forced expiratory flow (FEF50),
      75% forced expiratory flow (FEF75), maximal mid-expiratory flow (MMF), peak
      expiratory flow (PEF), expressions of BTLA, HVEM, IL-4, CD4(+);CD25(+);Treg and
      CD4(+);CD25(+);Foxp3(+); Treg significantly decreased, and TGF-beta1, IL-17
      significantly increased in MC group (P<0.01 or P<0.05). Compared with MC group,
      weight, levels of E, E/A, FEV1, FEF50, FEF75, PEF, BTLA, HVEM, IL-4,
      CD4(+);CD25(+);Treg and CD4(+);CD25(+);Foxp3(+); Treg significantly increased,
      and Mankin score, cardiacindex (CI), lung index (LI), TGF-beta1, IL-17
      significantly decreased in GS and XFC groups (P<0.01 or P<0.05); Compared with GS
      group, weight and Treg were significantly elevated in XFC group (P<0.01 or
      P<0.05). CONCLUSION: XFC can decrease Mankin scores of cartilage and improve
      cardiopulmonary function of KOA rats. Its mechanism may be enhancing BTLA-HVEM
      negative co-stimulatory signals, inducing Treg immune tolerance, up-regulating IL
      4, down-regulating IL-17, TGF-beta1, then to inhibit abnormal inflammatory immune
      response.

PMID- 23127400
TI  - [Effect of dexamethasone on expressions of TWEAK and Fn14 in the lung of
      asthmatic mice].
AB  - AIM: To investigate the effect of dexamethasone (Dex) on the expressions of TNF
      like weak inducer of apoptosis (TWEAK) and fibroblast growth factor-inducible
      immediate-early response protein 14 (Fn14) in the lung of asthmatic mice.
      METHODS: Ovalbumin (OVA) was used to induce asthma in BALB/c mice. Thirty-six
      female mice were randomly divided into control group (n=12),  asthmatic group
      (n=12) and Dex treated group (n=12). The airway inflammation was evaluated by HE
      staining. The expressions of TWEAK and Fn14 at mRNA and protein levels were
      detected by RT-PCR and immunohistochemistry,  respectively. RESULTS: Both mRNA
      and protein levels of TWEAK and Fn14 in the asthmatic model group were
      significantly higher than those of control group (P<0.01),  and both mRNA and
      protein levels of TWEAK and Fn14 in the Dex treated group were significantly
      lower than those of asthmatic group (P<0.01). CONCLUSION: Dex can reduce the
      airway inflammation through inhibiting the expressions of TWEAK and Fn14.

PMID- 23127401
TI  - [Mig-7 enhances vasculogenic mimicry in gastric cancer cells].
AB  - AIM: To observe vasculogenic mimicry (VM) in gastric cancer cells in vitro,  and
      explore the possible underlying mechanisms by transfecting SGC7901 cells with Mig
      7-siRNA and observing the impact on VM formation. METHODS: The capability of VM
      formation in differently differentiated gastric cancer cells were observed by
      light microscopy and scanning electron microscopy in a three-dimensional culture
      system. The expression of Mig-7 was detected. The impact of transfection with Mig
      7-siRNA into SGC7901 cells on the abilities of VM formation,  invasion and
      migration were also examined. The expressions of Mig-7,  phosphor-extracellular
      regulated protein kinases 1, 2 (p-ERK1/2) and matrix metalloproteinase-2 (MMP-2)
      in SGC7901 cells were analyzed by Western blotting. RESULTS: VM formation was
      observed in poorly differentiated MKN45 and moderately differentiated SGC7901
      cells,  but not in well differentiated MKN28 and normal GES-1 cells in vitro;  
      Mig-7 was expressed in MKN45 and SGC7901 cells,  but not in MKN28 and GES-1
      cells;   the abilities of VM formation,  invasion and migration were changed by
      transfection with Mig-7-siRNA into SGC7901 cells. The formation of VM was reduced
      by down-regulating the expressions of p-ERK1/2 and MMP-2 protein in SGC7901
      cells. CONCLUSION: Mig-7 is expressed in gastric cancer cells which are able to
      form VM. The formation of VM is inhibited by reducing the expression of Mig-7 in
      gastric cancer cells,  which might be mediated by down-regulating the expressions
      of p-ERK1/2 and MMP-2 proteins.

PMID- 23127402
TI  - [Resveratrol stimulates extracellular matrix synthesis in degenerative nucleus
      pulposus cells via upregulation of SIRT1].
AB  - AIM: To study the impact of resveratrol (RES) on the synthesis of extracellular
      matrix (ECM) in degenerative nucleus pulposus cells (DNPCs). METHODS: Human
      degenerative nucleus pulposus tissues were isolated,  identified through
      monolayer culture,  and cultivated in alginate. Primary alginate-cultured DNPCs
      were irritated by 0,  12.5,  25,  50,  100 and 200 MUmol/L RES for 12,  24 and 48
      h,  respectively. The protein expressions of silent mating type information
      regulation 2 homolog 1 (SIRT1),  Colla2alpha1 and aggrecan were examined by
      Western blotting,  and the expression level of SIRT1 mRNA was measured through
      real-time fluorescence quantitative PCR. The cells were transfected by SIRT1
      siRNA and cultured in 100 MUmol/L RES for 24 h. Then the protein expressions of
      Colla2alpha1 and aggrecan were observed. RESULTS: RES up-regulated the
      expressions of SIRT1 at mRNA and protein levels,  and promoted the expression of
      DNPCs-synthesized ECM,  which were significantly different from the control group
      (P<0.05). After the expression of SIRT1 was silenced by siRNA,  RES was added for
      irritation. The protein expressions of Colla2alpha1 and aggrecan were
      significantly reduced in comparison with the control group (P<0.05). CONCLUSION:
      RES can stimulate the synthesis of ECM in DNPCs,  which exhibits a dose-effect
      relationship. This regulating effect is related to the activity of SIRT1.

PMID- 23127403
TI  - [Construction of a recombinant stable Ba/F3 cell strain containing Tpr-Met].
AB  - AIM: To construct a stable cell strain encoding tumor-associated fused gene which
      expresses oncoprotein Tpr-Met. METHODS: We transfected Tpr-Met vector into Ba/F3
      cells and screened the cell strain stably expressing Tpr-Met. The interleukin 3
      (IL-3) independent proliferation of the cells was measured using the MTS assay.
      The expression of Tpr-Met,  the activity of downstream signal transduction
      pathway and SU11274-induced inhibition of the signal pathway were investigated by
      Western blotting. RESULTS: We obtained a Ba/F3 cell strain stably expressing Tpr
      Met. The cells presented IL-3 independent proliferation,  suggesting a malignant
      transformation of the cell line. In Tpr-Met transformed Ba/F3 cells,  the
      phosphorylation of Met and ERK were enhanced;  however,  specific c-Met inhibitor
      SU11274 suppressed the cell proliferation and c-Met phosphorylation. CONCLUSION:
      Tpr-Met transformed Ba/F3 strain has been successfully constructed.

PMID- 23127404
TI  - [Prokaryotic expression and purification of a tandem repeat of ovarian cancer
      antigen CA125 and preparation of its antiserum].
AB  - AIM: To establish a prokaryotic expression system of the tandem repeat of CA125
      (CA125R),  express and purify the recombinant CA125R protein,  prepare its
      antiserum. METHODS: The full gene sequence of one tandem repeat of CA125 was
      synthesized and cloned into pET-32a(+) to construct a prokaryotic expression
      vector of the CA125R protein (pET-CA125R). The pET-CA125R was transformed into
      E.coli BL21 (DE3) and the soluble expression conditions were optimized;  the pure
      recombinant CA125R protein was prepared by affinity Ni-NTA chromatography and
      identified by Western blotting. A rabbit was immunized with the pure recombinant
      CA125R protein to prepare its antiserum. RESULTS: The prokaryotic expression
      vector of CA125R was successfully constructed. The optimal soluble induction
      expression conditions were 0.5 mmol/L isopropyl beta-D-1-thiogalactopyranoside
      (IPTG) at 15DegreesCelsius for 6 h. Western blotting confirmed the pure CA125R
      recombinant protein of high purity. The prepared antiserum specifically
      recognized recombinant CA125R protein and natural CA125 glycoprotein. CONCLUSION:
      We successfully established the efficient prokaryotic expression system of the
      CA125R,  and prepared the recombinant CA125R protein of high purity and its
      antiserum.

PMID- 23127405
TI  - [Changes of heme oxygenase-1 expression in the nigrostriatal system of MPTP
      treated SAMP8 mouse].
AB  - AIM: To explore the relationship between the expression of hemeoxygenase-1 (HO-1)
      and the dopaminergic system impairment in MPTP-treated SAMP8 mice. METHODS: 6
      month-old male SAMP8 mice received MPTP (20 mg/kg) subcutaneous injection at 2-h
      intervals for 4 times,  and the control group was treated with an equal volume of
      normal  saline. Mice were sacrificed at 6 h,  24 h,  3 d and 8 d after the first
      injection for the detection of the changes of tyrosine hydroxylase (TH) and HO-1
      in the nigrostriatal system by immunohistochemistry and Western blotting.
      RESULTS: TH-positive neuronal loss was visible at 6 h (14.23%,  P<0.05),  24 h
      (23.85%,  P<0.01),  3 d (36.77%,  P<0.001),  and 8 d (45.90%,  P<0.001),  and the
      significant progression of dopaminergic neuronal loss occurred most prominently
      in the MPTP group from 24 h to 3 d (24 h vs 3 d,  P<0.05). There was a
      significant decrease of striatal TH immunoreactive cells  in the MPTP group
      (P<0.05). Additionally,  HO-1 positive cells were detected in striatum just only
      at 3 d,  with the increase of HO-1 protein expression in MPTP groups. Western
      blot analysis showed no change of HO-1 protein levels in the midbrain after MPTP
      treatment compared to those of the normal  saline group. CONCLUSION: MPTP caused
      the loss of dopaminergic neuron number and the decrease of TH protein levels in
      SAMP8 mice. The up-regulation of HO-1 was ephemeral,  and its effects related
      with Parkinson's disease was limited in this study.

PMID- 23127406
TI  - [Role of Toll-like receptor 4 in hyperoxia-exposed microglia injury].
AB  - AIM: To explore the role of Toll-like receptor 4 (TLR4) in the injury of
      microglia exposed to hyperoxia. METHODS: N9 microglia (TLR4 wild type) and EOC20
      microglia (TLR4 knock-out type) were exposed to 950 mL/L high oxygen respectively
      for different time periods to establish the high oxygen cell injury model.
      Expression of TLR4  mRNA and protein levels were detected by RT-PCR and Western
      blotting,  respectively. After intervention with the antioxidant NAC (N-acetyl-L
      cysteine,  N-acetyl half pathway of ammonia),  we detected the activity of
      reactive oxygen species (ROS),  NF-kappaB and the expression of TNF-alpha in
      cellular supernatant of N9 and EOC20 microglia exposed to hyperoxia for 2,  6 h.
      RESULTS: Expression of TLR4 mRNA in N9 microglia exposed to hyperoxia increased
      in a time-dependent manner,  meanwhile,  activity of ROS,  NF-kappaB and
      expression of TNF-alpha in microglia exposed to hyperoxia significantly increased
      (P<0.05),  while decreased (P<0.05) after intervention with the antioxidant NAC.
      The activity of ROS,  NF-kappaB and the expression of TNF-alpha were lower in
      EOC20 microglia than in N9 microglia after exposed to hyperoxia for different
      time periods (P<0.05). CONCLUSION: TLR4 involves in the regulation of forming ROS
      and the release of inflammatory markers on microglia after exposed to hyperoxia.

PMID- 23127407
TI  - [Differentiation of ectomesenchymal stem cells into dendritic cells in vitro
      induced by cytokines].
AB  - AIM: To induce the differentiation of ectomesenchymal stem cells (EMSCs) into
      dentritic cells (DCs) in vitro. METHODS: The EMSCs were cultured for 17 days 
      continuously in RPMI1640 medium containing 100 ng/mL rat recombinant GM-CSF and
      200 U/mL rat recombinant IL-3. On the 19th day,   they were induced by rat
      recombinant TNF-alpha. The characteristics of the induced EMSCs were observed in
      aspects of morphology,   ultrastructure,   surface marker,   mixed lymphocyte
      reaction and secretion of IL-12. The bone marrow-derived mesenchymal stem cells
      (BMSCs) of Sprague Dawley rat were used as controls. RESULTS: The induced EMSCs
      exhibited slender pseudopodia,   burr and partial adherent growth. Scanning
      electron microscopy showed that the cells displayed processes and pseudopodia.
      The expressions of surface markers of induced EMSCs were similar to those of
      BMSCs-induced DCs. The mixed lymphocyte reaction assay revealed that the EMSCs
      stimulated the proliferation of lymphocytes. The induced EMSCs displayed the
      ability of IL-12 secretion. CONCLUSION: EMSCs can be differentiated into DCs by
      induction in vitro.

PMID- 23127408
TI  - [Expression and antigen binding activity of anti-human CD86 diabody].
AB  - AIM: To construct a recombinant eukaryotic expression vector of anti-human CD86
      diabody gene and express anti-CD86 diabody through Chinese hamster ovary (CHO)
      cells,   then analyze the capability of the diabody to recognize the tumor cells
      expressing CD86 and its biological effect. METHODS: The antibody heavy and light
      chain viable region gene (V(H); and V(L);) were cloned from hybridoma cell 1D1
      which secreted anti-human CD86 monoclonal antibody. Anti-human CD86 diabody gene
      V(H);-(GGGGS)-V(L); was constructed by SOE-PCR. Then we inserted it into
      eukaryotic expression vector to construct a recombinant vector pIRES2-EGFP/CD86
      diabody. The recombinant vector was transfected into CHO cells with
      Lipofectamine(TM); 2000,   and the cell clones secreting CD86 diabody were
      screened by G418. We used IMAC to purify CD86 diabody and quantified its
      concentration by BCA method. The capability of the diabody to recognize the CD86
      expressed on Raji and Daudi was analyzed through flow cytometry. After Raji cells
      were treated with CD86 diabody for 72 h,   its proliferation inhibiting effect
      was investigated by MTT assay. RESULTS: We have obtained one CHO cell line that
      stably secreted CD86 diabody. The concentration of CD86 diabody after
      purification was 5.24 mg/L. The positive rates of CD86 diabody to recognize Raji
      and Daudi were 77.2% and 70.6%,   respectively. After CD86 diabody treatment for
      72 h,   the inhibition rate of Raji cells was 37%. CONCLUSION: The anti-human
      CD86 diabody which we obtained successfully could recognize CD86 expressed on
      tumor cells specifically,   and inhibit the proliferation of these tumor cells
      effectively.

PMID- 23127409
TI  - [Preparation,  identification and application  of   monoclonal antibody against
      matrix metalloproteinases-2].
AB  - AIM: To prepare and characterize monoclonal antibodies against matrix
      metalloproteinase-2 (MMP-2),  check its expression in the tissues of human
      ovarian cancer and transplanted tumors in nude mice. METHODS: MMP-2 were linked
      to the carrier protein bovine serumalbumin (BSA) and keyhole limpet hemocyanin
      (KLH) using glutaraldehyde method to obtain MMP-2-BSA and MMP-2-KLH, 
      respectively. The anti-MMP-2 monoclonal antibody was obtained through hybridoma
      technique. We established the cell strains secreting mAb by hybridoma technique
      and prepared the mAb by induction of ascites in vivo. The prepared mAb was
      purified by salting out with ammonium sulfate and identified by ELISA and Western
      blotting. We compared the mAb and commercial polyclonal antibody by
      immunohistochemistry and detected the expressions of MMP-2 and CA125 in ovarian
      cancer issues and transplanted tumor. RESULTS: The artificial antigen and 3
      hybridoma cell lines secreting monoclonal antibodies (mAb) against MMP-2 were
      obtained. The subclasses of mAb were all  IgG1. The titer of peritoneal exudates
      was 1:1*10(6);. The expressions of MMP-2 and CA125 in transplanted tumor and
      ovarian cancer tissues were all high. The positive expression rate of MMP-2
      checked using generated antibody was 71.2%(57/80) in ovarian cancer tissues and
      16.67% (5/30) in normal tissues,  with significant difference between them
      (P<0.01). In early stage,  the positive rate of MMP-2 and CA125 combined
      detection was higher than that of CA125 detection alone (P<0.01). The mAb was
      suitable for detecting the expression of MMP-2 in human tissues and gave results
      consistent with commercial polyclonal antibody. The mAb was more specific than
      commercial mAb (P<0.01). CONCLUSION: The anti-human MMP-2 mAb is successfully
      prepared,  which may serve as a valuable tool in the functionaI studies of
      ovarian cancer.

PMID- 23127410
TI  - [Effect of XPA expression on the chemotherapy sensitivity of A549/DDP cells].
AB  - AIM: To investigate the influence on platinum-based chemotherapy sensitivity by
      silencing xeroderma pigmentosum group A (XPA) gene expression in non-small cell
      lung cancer (NSCLC) drug resistance cell lines (A549/DDP). METHODS: We detected
      the expression of XPA in lung normal and tumor tissues by immunohistochemistry, 
      quantitative real-time PCR (qPCR) and Western blotting. We silenced XPA
      expression in A549/DDP cells by XPA-shRNA transfection,  and detected the
      expression of XPA by qPCR and Western blotting.  The cell sensitivity to
      cisplatin and the apoptosis of A549/DDP cells transfected with XPA-shRNA were
      determined by MTT assay. RESULTS: The expression of XPA was higher in NSCLC
      tissues than that in normal lung tissues. Silencing XPA gene increased the
      apoptosis and sensitivity of A549/DDP cells to cisplatin. CONCLUSION: Silencing
      XPA gene can partly reverse the cisplatin resistance in human cisplatin-resistant
      NSCLC cell line A549/DDP.

PMID- 23127411
TI  - [Detection and clinical significance of Th1/Th2 cytokines in patients with
      idiopathic thrombocytopenic purpura].
AB  - AIM: To observe Th1 (IL-2 and IFN-gamma) and Th2 (IL-4,  IL-10) cytokine changes
      in patients with idiopathic thrombocytopenic purpura (ITP) and explore the
      correlation between ITP development and Th1/Th2. METHODS: A total of 30 patients
      with ITP and 26 healthy volunteers were enrolled in this study. Serum levels of
      IL-2,  IFN-gamma,  IL-4,  and IL-10 were detected by enzyme-linked immunosorbent
      assay (ELISA) before and after treatment. RESULTS: The serum levels of IFN-gamma
      and IL-2 in patients with ITP before the glucocorticoid treatment were
      significantly higher than those after the treatment and in the control groups
      (P<0.05),  while the serum levels of IL-4 and IL-10 in patients with ITP before
      treatment were significantly lower than those after the treatment and in the
      control group (P<0.05). CONCLUSION: Th1/Th2 imbalance plays a prominent role in
      the development of ITP,  and glucocorticoid treatment helps to restore the
      Th1/Th2 in the patients with ITP.

PMID- 23127412
TI  - [The subpopulation  CD4(+); CD25(+); Foxp3(+);/CD127(low/-); regulatory T cells
      in peripheral blood of HIV-infected patients correlated with disease
      progression].
AB  - AIM: To explore the subpopulation of CD4(+); CD25(+); Foxp3(+); regulatory T
      cells (Treg),  CD4(+); CD25(+); CD127(low/-); Treg in peripheral blood of HIV
      infected patients and study its correlation with other immune indicators.
      METHODS: We enrolled 68 cases of HIV/AIDS patients without anti-HIV treatment [29
      cases of long-term non-progressive (LTNP) group,  27 cases of typical progressive
      HIV infection group and 12 cases of AIDS group] and 20 healthy individuals as a
      control group.  Blood samples of these cases were analyzed by flow cytometry
      after immunofluorescent staining to determine the levels of CD4(+); T cells, 
      CD8(+); T cells,  NK cells and CD4(+); CD25(+); Foxp3(+);/CD127(low/-); Treg.
      RESULTS: Except CD8(+); T cells,  the levels of CD4(+); T,  NK cells and
      CD4(+);/CD8(+); in peripheral blood of HIV/AIDS patients were significantly lower
      than those in the control group (P<0.05);  With the progression of disease,  the
      percentage and absolute count of CD4(+);T cells,  the absolute counts of CD8(+);T
      cells and NK cells,  and CD4(+);/CD8(+); T cell ratio in the LTNP group,  HIV
      group and AIDS group decreased gradually,  while the percentage of CD8(+);T cells
      increased gradually. Our multiple comparison analysis revealed that the
      percentages of CD4(+); CD25(+); Foxp3(+); Treg and CD4(+); CD25(+); CD127(low/-);
      Treg in CD4(+); T cells were significantly different among groups (P<0.05). With
      the progression of disease,  the percentages of CD4(+); CD25(+); Foxp3(+); Treg
      and CD4(+); CD25(+); CD127(low/-); Treg increased gradually;  in addition,  the
      difference in the absolute count of CD4(+); CD25(+); Foxp3(+);/CD127(low/-); Treg
      was not statistically significant between LTNP group and healthy control
      group(P>0.05),  so was between HIV and AIDS groups (P>0.05);  no significant
      difference was found in every other two groups (P<0.05);  the absolute count of
      CD4(+); CD25(+); Foxp3(+);/CD127(low/-); Treg decreased gradually. CONCLUSION:
      CD4(+); CD25(+); Foxp3(+);/CD127(low/-); Treg may play a role in the
      immunopathogenesis of persistent HIV infection.

PMID- 23127413
TI  - [Primary culture and biological characteristics of cardiac fibroblasts of adult
      mice].
AB  - AIM: To establish a set of reliable methods of isolation,  culture and
      characterization of cardiac fibroblasts from adult mice. METHODS: Fibroblasts
      were isolated from adult mice and cultured using combined trypsin-type II
      collagenase digestion method or tissue block  culture method. The cell growth of
      cardiac fibroblasts was observed under an  inverted  phase contrast  microscope.
      Cell viability of the different cell passages was evaluated by Trypan blue
      staining. The proliferation of cardiac fibroblasts was analyzed by   growth 
      curve,  MTT assay and DNA cell cycle analysis,  respectively,  to observe the
      effects of different culture media on the growth of cardiac fibroblasts. The
      expressions of vimentin,  fibronectin and discoidin domain receptor 2  (DDR2) on
      the cardiac fibroblasts were observed by immunofluorescence staining. RESULTS:
      After 1 d culture with the enzyme digestion method,  the adherent cells were
      ellipse  observed under an inverted phase contrast     microscope and after 3 d, 
      cells  were  spindle  and    grew quickly. But only after 4 d isolation and
      culture by the block    culture method,  it was observed that cells grew from the
      border of tissues  and after 7 d,  the cells started to amplify gradually. The
      cell viability rate of both culture methods were more than 97%.  Growth    curve 
      of the third passage presented a "S" shape by both methods. MTT assay showed the
      optimal cell proliferation value on day 3 to day 5. The ratio of G0-G1 phase and
      S+G2+M phase were respectively 62.61% and 30.87% by enzyme digestion method,  and
      69.24% and 28.05% by block  culture method. Log phase was found in cardiac
      fibroblasts cultured in HG/DMED supplemented with 10% fetal bovine serum. The
      cell colonies like a swirl were observed at the third passage by HE staining.
      Under a fluorescent microscope,  the cells were highly positive for the
      expressions of vimentin,  fibronectin and DDR2 which were the classical phenotype
      of the fibroblasts. CONCLUSION: The cardiac fibroblasts could be effectively
      obtained by both enzyme digestion and block  culture methods. Compare to the
      block culture method,  the cells isolated by the combined enzyme digestion method
      expressed the higher levels of fibroblasts markers such as vimentin,  fibronectin
      and DDR2.

PMID- 23127414
TI  - [Construction  of recombinant lentiviral vector containing shRNA for human
      neuropilin-1 gene].
AB  - AIM: To construct and identify a recombinant lentiviral vector containing shRNA
      for human neuropilin-1 (NRP-1) gene. METHODS: Four shRNA targeting the NRP-1 mRNA
      were designed to construct the pGCSIL-RFP-shNRP1 lentivirus vectors. The positive
      clone was chosen and confirmed by PCR and DNA sequencing. 293T cells were
      cotransfected with pGCSIL-RFP-shNRP1,  pHelper1.0 and pHelper 2.0 to package the
      lentivirus and the titer of the virus was tested. After lentivirus-shRNA and over
      expression plasmid containing NRP-1 were transfected into 293T cells,  Western
      blotting was used to determine the expression of Flag gene in order to observe
      the inhibited efficacy of relative NRP-1 expression. RESULTS: PCR analysis and
      DNA sequencing demonstrated that the shRNA sequence was consistent with the human
      NRP-1. The titer of the recombinant lentiviral vector was 1*10(9); Tu/mL. The
      relative expression of NRP-1 protein in the transfected cells significantly
      decreased after treated with lentiviral-shRNA. CONCLUSION: We have constructed
      successfully the effective recombinant lentiviral vector containing shRNA for
      human NRP-1 gene.

PMID- 23127415
TI  - [Construction  of lentivirus-mediated short hairpin RNA targeting human STAT3
      gene].
AB  - AIM: To construct and identify a lentivirus-mediated short hairpin RNA (shRNA)
      targeting human signal transducer and activator of transcription 3 (STAT3) gene.
      METHODS: The shRNA chains targeting to human STAT3 gene were designed and
      synthesized,  and then inserted into lentivirus expression vector pSicoR
      containing U6 promoter and green fluorescent protein (GFP) gene by gene
      recombination technique. The constructed recombinant plasmid pSicoR-STAT3-shRNA
      was identified by double restriction enzyme digestion   and DNA sequencing,  and
      then mixed with the 3rd generation of lentiviral packaging system and co
      transfected to HEK293 cells using new generation of Roche X-tremeGENE HP DNA
      Transfection Reagent  mediated transfection method. RT-PCR and Western blotting
      were employed to detect the expressions of STAT3 at mRNA and protein levels, 
      respectively. Negative plasmid transfected into the same cell line was used as a
      control group. RESULTS: Restriction analysis and sequencing proved that the
      recombinant plasmid pSicoR-STAT3-shRNA was constructed correctly. Lentivirus
      particles were successfully packaged in HEK293 cells with high titer. The
      expressions of STAT3 at mRNA and protein levels in the transfected HEK293 cells
      were weaker than those of the control group (P<0.05). CONCLUSION: The lentivirus
      mediated shRNA targeting human STAT3 gene is successfully constructed.

PMID- 23127416
TI  - [Prokaryotic expression,  purification and  identification of  recombinant
      staphylokinase-HC fusion protein].
AB  - AIM: To construct the prokaryotic expression plasmid pEGX-6P-1-SAK-HC,  express
      it in E.coli,  and identify its biological activity. METHODS: The fusion gene
      (SAK-HC) was obtained by overlap-extension PCR and then inserted into prokaryotic
      soluble pEGX-6P-1 vector with GST tag to construct expression plasmid (pEGX-6P-1
      SAK-HC). GST-SAK-HC was expressed by E.coli B834 (DE3) under the induction of
      IPTG and purified by Glutathion-Sepharose 4B (GST) affinity chromatography and
      negative-ion exchange column (DEAE) chromatography. PreScission protease was used
      to remove the GST tag. The purity of the fusion protein was analyzed by SDS-PAGE
      and the fibrinolytic activity of SAK-HC in vitro was characterized by soluble
      fibrin plate method. RESULTS: PCR,  sequencing and restriction enzyme digestion
      analysis demonstrated that the recombinant plasmid was constructed successfully.
      The fusion protein was expressed in E.coli B834 (DE3),  M(r); being 36 000 as
      shown by SDS-PAGE. After purified by GST affinity and DEAE chromatography,  SAK
      HC fusion protein of high purity was obtained from the cell supernantants. In
      vitro experiments showed that the fibrinolytic activity of the recombinant SAK-HC
      was about 9.4*10();4 IU/mg. CONCLUSION: The SAK-HC fusion protein we obtained was
      successfully expressed in E.coli and exhibited a fibrinolytic activity as high as
      the urokinase standard,  which offers a base for the identification of
      immunogenicity of the fusion protein.

PMID- 23127417
TI  - Predicting fluctuations in widespread interest: memory decay and goal-related
      memory accessibility in internet search trends.
AB  - Memory and interest respond in similar ways to people's shifting needs and
      motivations. We therefore tested whether memory and interest might produce
      similar, observable patterns in people's responses over time. Specifically, the
      present studies examined whether fluctuations in widespread interest (as measured
      by Internet search trends) resemble two well-established memory patterns: memory
      decay and goal-related memory accessibility. We examined national and
      international events (e.g., Nobel Prize selections, holidays) that produced
      spikes in widespread interest in certain people and foods. When the events that
      triggered widespread interest were incidental (e.g., the death of a celebrity),
      widespread interest conformed to memory decay patterns: It rose quickly, fell
      slowly according to a power function, and was higher after the event than before
      it. When the events that triggered widespread interest were goal related (e.g.,
      political elections), widespread interest conformed to patterns of goal-related
      memory accessibility: It rose slowly, fell quickly according to a sigmoid
      function, and was lower after the event than before it. Fluctuations in
      widespread interest over time are thus similar to standard memory patterns
      observed at the individual level due perhaps to common mechanisms and functions.

PMID- 23127418
TI  - When cheating would make you a cheater: implicating the self prevents unethical
      behavior.
AB  - In 3 experiments using 2 different paradigms, people were less likely to cheat
      for personal gain when a subtle change in phrasing framed such behavior as
      diagnostic of an undesirable identity. Participants were given the opportunity to
      claim money they were not entitled to at the experimenters' expense; instructions
      referred to cheating with either language that was designed to highlight the
      implications of cheating for the actor's identity (e.g., "Please don't be a
      cheater") or language that focused on the action (e.g., "Please don't cheat").
      Participants in the "cheating" condition claimed significantly more money than
      did participants in the "cheater" condition, who showed no evidence of having
      cheated at all. This difference occurred both in a face-to-face interaction
      (Experiment 1) and in a private online setting (Experiments 2 and 3). These
      results demonstrate the power of a subtle linguistic difference to prevent even
      private unethical behavior by invoking people's desire to maintain a self-image
      as good and honest.

PMID- 23127419
TI  - Phytoplankton composition indicators for the assessment of eutrophication in
      marine waters: present state and challenges within the European directives.
AB  - Several legislations worldwide require assessing the health status of marine
      ecosystems. In Europe, the Water Framework Directive (WFD) and the Marine
      Strategy Framework Directive (MSFD) demand the evaluation of the status with the
      overall objective of achieving at least "Good Status", by 2015 and 2020,
      respectively. For this purpose, Member States are required to evaluate different
      biological, physico-chemical and hydro-morphological quality elements (WFD), or
      qualitative descriptors (MSFD). The assessments of both, the phytoplankton
      element and the eutrophication descriptor should include several attributes,
      namely phytoplankton biomass, composition, abundance and blooms. However, few
      composition-based indicators have been proposed. Principally, phytoplankton still
      relies on chlorophyll-a concentration measurements, mainly due to the high cost
      of collecting information on this element and the difficulties establishing
      significant pressure-impact relationships. This investigation describes the
      difficulties in the development of a phytoplankton community composition
      indicator, the state of the art and the main challenges for the future.

PMID- 23127420
TI  - Bringing words back to mind - Improving word production in semantic dementia.
AB  - Patients with semantic dementia (SD) have significant impairments in naming and
      comprehension, but demonstrate relatively intact attention, everyday memory, and
      visuospatial skills. Given these preserved skills, attempts have been made to
      help re-build vocabulary in SD patients, with promising results. Such reports,
      however, are generally based upon only one or two cases and have employed
      variable retraining methods. It is thus unclear which elements of practice are
      crucial to success. Over two studies, we assessed four patients undergoing a word
      training program, who ranged in severity from mild to severe impairments to
      semantic knowledge. All four participants showed significant improvements in
      their ability to name trained items, with no changes in untrained items over the
      same time period. Improvements were evident within 3 weeks of practice, and could
      be established from a simple, repetitive practice of word-picture pairing,
      carried out at the participant's home. Strong effect sizes of the treatment were
      found in patients with severe deficits. Maintenance of learning was observed on
      some follow-up assessments, although continued practice is likely to be needed to
      sustain naming performance. Incorporating generation tasks into the practice may
      be assistive, but was not essential to success. These data support the utility of
      implementing simple home-practice programs even for patients with significant
      language deficits.

PMID- 23127421
TI  - Co-culture of healthy human keratinocytes and T-cells promotes keratinocyte
      chemokine production and RORgammat-positive IL-17 producing T-cell populations.
AB  - BACKGROUND: Both keratinocytes and T-cells are crucial players in cutaneous
      immune responses. We hypothesized that direct interactions between keratinocytes
      and T-cell subsets could shape the nature or strength of the local immune
      response. OBJECTIVE: We investigated direct interactions between keratinocytes
      and T-cell subsets, focused on keratinocyte chemokine production and T-cell
      phenotype and cytokine production. METHODS: A newly developed in vitro serum free
      co-culture model using primary keratinocytes and T-cells subsets from healthy
      human donors was used. Keratinocyte chemokine production was analyzed with
      luminex, T-cell phenotype and cytokine production were analyzed with flow
      cytometry. RESULTS: Our data show that upon co-culture with CD4(pos) or CD8(pos)
      T-cells primary human keratinocytes increased production of functionally active
      chemokines CCL2, CCL20 and CXCL10 and that regulatory T-cells did not regulate
      keratinocyte chemokine production. Next to that, we found that keratinocytes
      skewed CD4(pos) and CD8(pos) T-cell populations toward an IL-17(pos) CCR6(pos)
      RORgammat(pos) phenotype in a cell-cell contact independent manner, and that Treg
      were able to decrease the absolute number of IL-17 producing T-cells in
      keratinocyte/T-cell co-cultures. Correspondingly, freshly isolated skin-derived T
      cell populations contained relatively high percentages of IL-17(pos) cells.
      CONCLUSION: We provide evidence that keratinocyte/T-cell communication may
      regulate leukocyte influx in the skin, and that keratinocytes enrich T-cell
      populations for Th17/Tc17 cells. Accumulation of Th17/Tc17 cells, but not
      chemokine production, appears under the control of regulatory T-cells.
      Dysregulation of these processes may well contribute to the pathophysiology of
      inflammatory skin diseases.

PMID- 23127422
TI  - The effect of biplane medial opening wedge high tibial osteotomy on
      patellofemoral joint indices.
AB  - PURPOSE: This study was designed to examine the effect of biplane medial opening
      wedge high tibial osteotomy (MOWHTO) on patellofemoral indices and posterior
      tibial slope. MATERIALS AND METHODS: Sixty-two knees (61 patients) underwent
      biplane MOWHTO for unicompartmental osteoarthritis of the knee. Patellar indices
      were measured by radiographic assessment postoperatively. The Merchant's views
      were used for patellar tilt and shift while standing lateral view radiographs
      were used for the patellar height analysis using the modified Blackburne-peel
      ratio (mBP). The patients were divided into two groups according to the change
      between the pre- and postoperative mechanical axis. Group A constituted the
      correction angle of equal more than 10 degrees , and group B of less than 10
      degrees . RESULTS: Group A demonstrated a significant change of mechanical axis
      and the tibial slope. Patellar indices including the patellar tilt, shift, and
      mBP did not show significant difference. Group B demonstrated the statistical
      significant difference in only the mechanical axis deviation. Patellar indices
      including the patellar tilt, shift, and mBP as well as the tibia slope did not
      show significant difference. When evaluated as a whole group, the mean shift in
      weight bearing line, patellar height (mBP), and tibial slope from preoperative to
      postoperative value was statistically significant. However, the patellar tilt and
      shift were not changed significantly. CONCLUSIONS: After biplane MOWHTO, patellar
      tilt and shift do not significantly change when measured on static mode supine X
      ray. However, patella was lowered and tibia slope increased after MOWHTO. LEVEL
      OF EVIDENCE: II.

PMID- 23127423
TI  - Mild cognitive impairment--the continuing challenge of its "real-world" detection
      and diagnosis.
AB  - Although mild cognitive impairment (MCI) is a controversial entity with variable
      application in clinical and epidemiological research, it remains an important
      construct in terms of targeting interventions to prevent dementia. However, very
      little is known about how MCI may be recognized during clinical attention in
      routine practice. This work was undertaken to summarize recent findings relevant
      to the presentation and initial detection of MCI. A narrative review is presented
      of literature relevant to the presentation and detection of MCI in primary care.
      Population screening for impaired cognitive function and/or informant-reported
      decline/impairment is unlikely to be feasible or acceptable. MCI detection will
      therefore rely largely on subjective memory complaint (SMC) as a presenting
      symptom, accepting the fact that, although possibly a valid self-appraisal of
      underlying function in older persons, SMC is heterogeneous in its etiology and
      poorly predicts medium-term dementia risk. SMC is common in older populations
      when asked about and is often concerning to the person acknowledging it. However,
      it is rarely reported to general practitioners. Help-seeking of this nature is
      influenced partly by the perceived severity of the symptom but also by contextual
      factors such as concerns about a family history of dementia, although very little
      research has investigated this. If an intervention were proven to be effective
      for preventing transition from MCI to dementia in the near future, there would be
      a serious lack of knowledge about how MCI can be identified in routine clinical
      practice.

PMID- 23127424
TI  - Protective effect of dendrodoine analog, an aminothiazole derivative against X
      radiation induced hepatocellular damage in mice.
AB  - This study evaluated the radioprotective effect of dendrodoine analog (DA)
      against radiation-induced damage in the liver of mice. The study was divided into
      two phases; in the first phase, the effective concentration of DA was fixed by
      performing a survival study. In the second phase, the fixed effective
      concentration of DA was orally administered to mice to evaluate its
      radioprotective efficacy by performing various assays. The results indicated that
      the radiation-induced decrease in the activities of antioxidant enzymes, increase
      in thiobarbituric acid reactive substances (TBARS) and comet parameters were
      altered by pre-administration with the effective concentration of DA which
      restored the antioxidant status to near normal and decreased the level of the
      TBARS and comet parameters. The histopathological examinations further confirmed
      the hepatoprotective effect of DA in mice. Thus, the current study showed DA to
      be an effective radioprotector against radiation induced damage in the liver of
      mice.

PMID- 23127425
TI  - From the editor's perspective....

PMID- 23127426
TI  - Utilizing clinical support staff and electronic health records to increase
      tobacco use documentation and referrals to a state quitline.
AB  - The purpose of this study was to determine if incorporation of a workflow in the
      electronic health record (EHR) that empowered medical assistants (MA) to become
      tobacco-cessation promoters, would increase tobacco documentation and referral
      for cessation counseling. MAs in three primary care centers were trained to ask
      every patient, at every visit, about tobacco use then document this status in the
      EHR. Patients ready to quit were electronically referred to the quitline for
      tobacco cessation counseling. Documentation of tobacco status, ongoing
      verification of tobacco use, and chief complaint recording was compared before
      and after the intervention. Logistic regression analysis indicated that after
      adjusting for differences between care centers, there were increased odds in
      initial documentation (OR = 1.52; 95% CI = 1.42 - 1.62) and ongoing verification
      (OR = 2.86; 95% CI = 1.42 - 1.62) in 2010 in comparison with 2009. Recording of
      tobacco cessation as the chief complaint in current smokers increased 91% (OR =
      1.91; 95% CI = 1.56 - 2.34). Documentation and referrals for smoking cessation
      can be increased in organizations using EHR by empowering MAs to promote tobacco
      cessation and providing electronic referral options.

PMID- 23127427
TI  - Risk attitude and preferences in person's hypothetically facing open repair of
      abdominal aortic aneurysm.
AB  - The aim of this study was to describe risk attitude and preference for treatment
      using a proxy measurement of a general population sample hypothetically facing
      treatment for open repair (OR) of abdominal aortic aneurysm (AAA). In a telephone
      interview, a standard gamble (SG) and a time trade-off (TTO) question were asked
      to elicit risk attitude and preference for treatment in a general population
      sample of 200 persons, stratified in four age groups. When facing the two
      questions of (1) either live a shorter life without an AAA compared to a longer
      life with an AAA (TTO) or (2) taking a risk of living with AAA compared to taking
      the risk with surgical treatment (SG), the oldest age group was neither willing
      to live a shorter life without AAA, nor willing to take a risk with surgical
      treatment to the same extent as the younger age groups: age 50-59 (TTO P = 0.03,
      SG P = < 0.001), age 60-69 (TTO P = 0.01, SG P = < 0.001), age 70-79 (TTO P =
      0.02, SG P = 0.002). These results suggest that persons in the age groups over 80
      years old in the general population sample are more inclined to go on living with
      an AAA without taking the immediate risk associated with OR as well as the
      postoperatively impaired health-related quality of life (HRQL). Preference for
      treatment in different age groups is important to consider during the decision
      making process, especially for patients over 80 years old. Patient education
      about treatment options, specific risks as well as postoperative impairment of
      HRQL is necessary in this process.

PMID- 23127428
TI  - Factors affecting medication adherence in patients with hypertension.
AB  - The aim of this study descriptive study was to evaluate concordance with
      medication and those factors that affect the use of medicine in patients with
      hypertension. Data were collected using a questionnaire completed by 750 patients
      with hypertension between December 25, 2003, and April 30, 2004, in an outpatient
      hypertension clinic in Erzincan, Turkey. It was found that 57.9% of the patients
      did not use their medicines as prescribed. Forgetfulness, aloneness, and
      negligence were ranked as the top three reasons for this non-concordance,
      accounting for almost half (49.3%) of all patients with hypertension studied;
      price (expensive medicines) accounted for another quarter (26.5%). A
      statistically significant relationship with non-concordance was found for age,
      education level and profession. Patients' lack of knowledge related to the
      complications of hypertension was also found to have a statistically significant
      relationship with not taking medicines as prescribed. Gender, location of
      residence and salary were not found to be statistically related to concordance.
      These results indicate the need to educate patients with hypertension on how to
      use their medicine regularly and indicate also the target populations for this.

PMID- 23127429
TI  - Dobutamine Cardiolite((r)) stress testing with low-level treadmill exercise
      demonstrates improved image quality, less medication and fewer patient side
      effects.
AB  - Some form of exercise is helpful to achieve target heart rate (THR) in patients
      undergoing dobutamine Technetium-99 Sestamibi (Cardiolite((r))) stress tests. The
      outcomes of low-level exercise (slow treadmill walking) and isometric exercises
      to achieve THR during dobutamine Cardiolite((r)) stress tests have not been
      examined. The purpose of this study was to determine if patients who walked on a
      treadmill during their dobutamine Cardiolite((r)) stress test had better outcomes
      than those who used isometric exercises. The outcomes measured were the amount of
      dobutamine and atropine sulfate (atropine) used, duration of dobutamine infusion
      and quality of cardiac images. A convenience sample of 30 patients per group who
      required a dobutamine Cardiolite(r) stress test was recruited from April to
      September, 2008. Descriptive statistics were reported for each group. The
      subjects who walked on the treadmill required a lower dose of dobutamine (P =
      0.028) and a decreased time of dobutamine infusion (P = 0.031) to achieve their
      target heart rate. Heart-to-liver ratio results (P = 0.08) and image quality (P <
      0.0001) were better with the subjects who walked on the treadmill. No difference
      in atropine usage was found in either group. These outcomes suggest that the
      patient who walked on a treadmill during the dobutamine Cardiolite((r)) stress
      test achieved the target heart rate faster, required less dobutamine and had
      better image quality than those who performed isometric exercises.

PMID- 23127430
TI  - Clinical guidelines: grading the evidence behind the practice.
AB  - Clinical practice guidelines are statements to assist in healthcare decisions for
      patients with the same illness or procedure. Guidelines comprise elements that
      describe different aspects of the patient's condition and the required care. Many
      organizations publish guidelines, including the Society for Vascular Nursing.
      Evidence is the foundation of guidelines and their practice recommendations. This
      evidence is primarily from research. Developing a grading system for the research
      and the associated practice elements improves the strength of a guideline's
      statements. This article discusses the grading system selected by the Society for
      Vascular Nursing (SVN) Practice and Research Committee when creating the
      forthcoming carotid stent nursing practice guideline.

PMID- 23127431
TI  - Review of an article: Surgery for small abdominal aortic aneurysms that do not
      cause symptoms by Filardo G, Powell JT, Martinez MA, and Ballard DJ (Cochrane
      Database of Systematic Reviews 2012, Issue 3. Art. No. CDOO1835.
      DOI:10.1002/14651858.CDOO1835.pub3).

PMID- 23127432
TI  - Quantifying the effect of repetitive transcranial magnetic stimulation in the rat
      brain by MUSPECT CBF scans.
AB  - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is used to treat
      neurological and psychiatric disorders such as depression and addiction amongst
      others. Neuro-imaging by means of SPECT is a non-invasive manner of evaluating
      regional cerebral blood flow (rCBF) changes, which are assumed to reflect changes
      in neural activity. OBJECTIVE: rCBF changes induced by rTMS are evaluated by
      comparing stimulation on/off in different stimulation paradigms using microSPECT
      of the rat brain. METHODS: Rats (n = 6) were injected with 10 mCi of (99m)Tc
      HMPAO during application of two rTMS paradigms (1 Hz and 10 Hz, 1430 A at each
      wing of a 20 mm figure-of-eight coil) and sham. SPM- and VOI-based analysis was
      performed. RESULTS: rTMS caused widespread significant hypoperfusion throughout
      the entire rat brain. Differences in spatial extent and intensity of
      hypoperfusion were observed between both stimulation paradigms: 1 Hz caused
      significant hypoperfusion (P < 0.05) in 11.9% of rat brain volume while 10 Hz
      caused this in 23.5%; the minimal t-value induced by 1 Hz was -24.77 while this
      was -17.98 due to 10 Hz. Maximal percentage of hypoperfused volume due to 1 Hz
      and 10 Hz was reached at tissue experiencing 0.03-0.15 V/m. CONCLUSION: High
      frequency (10 Hz) stimulation causes more widespread hypoperfusion, while 1 Hz
      induces more pronounced hypoperfusion. The effect of rTMS is highly dependent on
      the electric field strength in the brain tissue induced by the TMS coil. This
      innovative imaging approach can be used as a fast screening tool in quantifying
      and evaluating the effect of various stimulation paradigms and coil designs for
      TMS and offers a means for research and development.

PMID- 23127434
TI  - Radiologic case study. Osteomalacia.

PMID- 23127433
TI  - Efficient EGFR signaling and dorsal-ventral axis patterning requires syntaxin
      dependent Gurken trafficking.
AB  - Vesicle trafficking plays a crucial role in the establishment of cell polarity in
      various cellular contexts, including axis-pattern formation in the developing egg
      chamber of Drosophila. The EGFR ligand, Gurken (Grk), is first localized at the
      posterior of young oocytes for anterior-posterior axis formation and later in the
      dorsal anterior region for induction of the dorsal-ventral (DV) axis, but
      regulation of Grk localization by membrane trafficking in the oocyte remains
      poorly understood. Here, we report that Syntaxin 1A (Syx1A) is required for
      efficient trafficking of Grk protein for DV patterning. We show that Syx1A is
      associated with the Golgi membrane and is required for the transportation of Grk
      containing vesicles along the microtubules to their dorsal anterior destination
      in the oocyte. Our studies reveal that the Syx1A dependent trafficking of Grk
      protein is required for efficient EGFR signaling during DV patterning.

PMID- 23127435
TI  - Rivaroxaban, an oral, direct factor Xa inhibitor: a new option for
      thromboprophylaxis.

PMID- 23127436
TI  - Bone morphogenic protein 3 signaling in the regulation of osteogenesis.

PMID- 23127437
TI  - Do we need to treat tennis elbow?

PMID- 23127438
TI  - Novel technique for passing tendon grafts through bone tunnels.
AB  - Anatomic reconstruction in orthopedic surgery often requires the passage of soft
      tissue through bone tunnels. Difficulties may arise due to anatomic constraints
      surrounding the bone tunnels or the graft size. The authors present a novel
      technique for passing tendon grafts through bone tunnels that is simple, readily
      available, effective, and comparatively inexpensive.

PMID- 23127439
TI  - Novel technique for ulnar collateral ligament reconstruction of the elbow.
AB  - Ulnar collateral ligament (UCL) reconstruction of the elbow has been shown to
      restore function in overhead athletes with valgus instability. Since the initial
      description of using bone tunnels for reconstruction, many modifications to the
      surgical technique have been introduced, including the modified Jobe technique,
      the docking technique, fixation with interference screws, and button fixation.
      The authors introduce a technique that uses a button on each of the humeral and
      ulnar sides for fixation. This method allows proper tensioning of the graft and
      provides immediate secure fixation that relies on metal implants as opposed to
      sutures over bone bridges alone.

PMID- 23127440
TI  - Spinopelvic tumor resection and reconstruction.

PMID- 23127441
TI  - Ideal position for thumb interphalangeal arthrodesis in the era of smartphones
      and text communication.
AB  - The hypothesis of this study was that arthrodesis of the thumb interphalangeal
      joint at a degree of flexion greater than the recommended 0 degrees  to 15
      degrees  in the era of widespread use of handheld devices would potentially be
      more beneficial for the use of these devices. For patients who rely heavily on a
      smart-phone or handheld device and require dominant thumb arthrodesis, thumb
      interphalangeal arthrodesis at an angle of 10 degrees  or 30 degrees  will
      neither improve nor impede their use of the device.

PMID- 23127442
TI  - Two-stage revision anterior cruciate ligament reconstruction: indications,
      review, and technique demonstration.
AB  - Revision anterior cruciate ligament reconstruction has inherent technical
      challenges not encountered during primary reconstruction. Prior tunnel placement
      and tunnel lysis can significantly alter graft fixation, compromising patient
      outcome. Preoperative recognition of patients with existing tunnel overlap and
      severe tunnel lysis will allow appropriate surgical planning and patient
      counseling, optimizing patient outcome. When single-stage revision is not
      possible in the presence of significant tunnel overlap and lysis, performing a 2
      stage revision is recommended.

PMID- 23127444
TI  - Scaphoid waist fracture.

PMID- 23127445
TI  - Bone grafting in shoulder arthroplasty.
AB  - Shoulder arthroplasty is one of the fastest-growing fields in orthopedic surgery.
      Deficiency of the glenoid or humeral bone stock is a major challenge that can
      result from degenerative arthritis, component loosening or extraction, fracture,
      or malignancy. Approximately 15% of primary reconstructions will require bone
      grafting, and the rate is higher for revisions. The authors present a systematic
      review of the current literature focused on the indications for and results of
      bone grafting techniques. This provides the practicing surgeon with a set of
      strategies to address bone loss in the primary and revision settings, whether
      using an anatomic or reverse design.

PMID- 23127446
TI  - Ceramic-on-ceramic total hip arthroplasty: incidence and risk factors of bearing
      surface-related noises in 125 patients.
AB  - The ceramic-on-ceramic bearing surface has high wear resistance and good
      biocompatibility in total hip arthroplasty (THA). However, the postoperative
      noise problem has been an important issue. The purpose of this retrospective
      study was to determine the incidence and risk factors of bearing surface-related
      noises in patients with third-generation ceramic-on-ceramic THAs. One hundred
      twenty-five patients (143 hips) with ceramic-on-ceramic THAs were included in the
      study and followed to obtain noise and functional results. Patient factors,
      including sex, age, height, weight, body mass index, diagnosis, and postoperative
      range of motion, and surgical factors, including cup inclination, ceramic head
      size and length, and size of cup related to noises, were recorded. Mean follow-up
      was 4.2 years (range, 2-10 years). Mean Harris Hip Score was 94 points (range, 68
      100 points) at latest follow-up. One (0.8%) patient had radiological evidence of
      osteolysis, and 4 (3.2%) patients had hip dislocation. No hip sustained a
      fracture of the ceramic component. Eight (6.4%) patients developed noise at their
      hips, including clicking in 4, grinding in 2, and snapping in 2. No patient
      developed squeaking hips or underwent revision surgery because of noisy hips.
      Younger patients (P=.01), a diagnosis of osteonecrosis (P=.014), a 28-mm ceramic
      head (P=.042), and a higher hip range of motion postoperatively (P=.001) were
      related to noise in ceramic-on-ceramic THAs. The study showed third-generation
      ceramic-on-ceramic THAs had a low incidence of noise problems. However, long-term
      follow-up is necessary to determine the clinical relevance.

PMID- 23127447
TI  - Changing transfusion practice in total hip arthroplasty: observational study of
      the reduction of blood use over 6 years.
AB  - Patients undergoing primary total hip arthroplasty (THA) have historically been
      over-transfused. In a district general hospital setting, the authors observed a
      significant downward trend in blood transfusion requirements in these patients
      over 6 years after a change in transfusion policy. The purpose of this study was
      to retrospectively analyze the change in transfusion practice and present the
      results of the restrictive transfusion policy. All patients undergoing primary
      THA between January 2003 and December 2008 were identified from hospital records.
      Pre- and postoperative hemoglobin levels, transfusion trigger hemoglobin, blood
      transfusion requirements, patient age and sex, 30-day mortality, and length of
      stay data were analyzed for all patients. A total of 1169 primary THAs were
      performed. Annual allogeneic blood transfusion requirements reduced progressively
      from 151 units in 2003 to 90 units in 2008 despite an increase in the number of
      patients undergoing THA. During this period, the proportion of patients
      transfused decreased from 35% to 17%. A reduction of mean transfusion trigger
      hemoglobin from 79 to 73 g/L was observed over the study period. No patient
      experienced any significant complications as a result of undertransfusion. The
      authors' institution has steadily restricted the use of blood transfusion in
      patients undergoing THA to those symptomatic of anemia. Increasing confidence
      among medical and nursing staff that reduced postoperative hemoglobin levels can
      be safely tolerated has resulted in a 55% reduction in blood transfusion in
      patients undergoing THA with no other change of practice.

PMID- 23127448
TI  - Use of Redon drains in primary total hip arthroplasty has no clinically relevant
      benefits.
AB  - Although no proven evidence exists for the use of drainage in primary total hip
      arthroplasty, such drainage is routinely used. This prospective, randomized study
      comprised 80 patients who underwent a non-cemented total hip arthroplasty using a
      minimally invasive anterolateral approach. Patients were divided into 2 groups of
      40: group 1 underwent drainage treatment and group 2 underwent no drainage
      treatment. No selection of patients occurred by age, sex, or body mass index.
      Blood loss was not significantly different between groups 1 (mean blood loss, 0.9
      L [range, 0.3-2.1 L]) and 2 (mean blood loss, 0.9 L [range, 0.3-2.4 L]) (P=.7).
      On postoperative day 1, patients who underwent drainage treatment reported
      significantly more pain at rest (P=.01) and under stress (P=.03). The same
      finding was observed on postoperative day 4 (at rest, P=.04; under stress,
      P=.02). The nonuse of drainage significantly reduced operative time by 72 seconds
      (P=.01). Patients without drainage treatment had significantly larger hematomas
      than patients with drainage (mean, 43.7 cm(2) [range, 0-343 cm(2)] vs mean, 40.1
      cm(2) [range, 0-514 cm(2)], respectively) (P=.03). No clinically relevant
      benefits associated with the use of drainage were identified. The increased size
      of the hematoma was not reflected in patient comfort. The authors consider the
      use of drainage in primary total hip arthroplasty unnecessary.

PMID- 23127449
TI  - Template-directed instrumentation in total knee arthroplasty: cost savings
      analysis.
AB  - The use of digital radiography and templating software in total knee arthroplasty
      (TKA) continues to become more prevalent as the number of procedures performed
      increases every year. Template-directed instrumentation (TDI) is a novel approach
      to surgical planning that combines digital templating with limited intraoperative
      instruments. The purpose of this study was to evaluate the financial implications
      and radiographic outcomes of using TDI to direct instrumentation during primary
      TKA. Over a 1-year period, 82 consecutive TKAs using TDI were retrospectively
      reviewed. Patient demographics and preoperative templated sizes of predicted
      components were recorded, and OrthoView digital planning software (OrthoView LLC,
      Jacksonville, Florida was used to determine the 2 most likely tibial and femoral
      component sizes for each case. This sizing information was used to direct
      component vendors to prepare 3 lightweight instrument trays based on these sizes.
      The sizes of implanted components and the number of total trays required were
      documented. A cost savings analysis was performed to compare TDI and non-TDI
      surgical expenses for TKA. In 80 (97%) of 82 cases, the prepared sizes determined
      by TDI using 3 instrument trays were sufficient. Preoperative templating
      correctly predicted the size of the tibial and femoral component sizes in 90% and
      83% of cases, respectively. The average number of trays used with TDI was 3.0
      (range, 3-5 trays) compared with 7.5 (range, 6-9 trays) used in 82 preceding non
      TDI TKAs. Based on standard fees to sterilize and package implant trays
      (approximately $26 based on a survey of 10 orthopedic hospitals performing TKA),
      approximately $9612 was saved by using TDI over the 1-year study period. Overall,
      digital templating and TDI were a simple and cost-effective approach when
      performing primary TKA.

PMID- 23127450
TI  - Arthroscopic excision of os acromiale: effects on deltoid function and strength.
AB  - Arthroscopic excision of os acromiale is a feasible alternative to open excision
      or fusion. This article describes the authors' experience with 28 patients (31
      shoulders) who underwent arthroscopic excision of os acromiale and its effect on
      shoulder pain and function, with specific emphasis on deltoid strength
      measurement. Thirty-one os acromiale (all persistent unfused pre- and meso
      acromions) in 28 patients were excised arthroscopically. Sixteen patients
      underwent concomitant rotator cuff repair (9 arthroscopic and 7 mini-open). At an
      average follow-up of 41 months, the patients were assessed using the American
      Shoulder and Elbow Surgeons (ASES) score, and deltoid function and strength were
      measured. Pain was completely alleviated postoperatively in 20 (65%) shoulders,
      and 9 (29%) shoulders had less pain postoperatively. Pain worsened
      postoperatively in 2 patients, both of whom had features of glenohumeral
      arthritis at arthroscopy. Average postoperative ASES score (80.33) was
      significantly improved compared with the average preoperative score (33.71). No
      significant loss of deltoid strength occurred compared with the contralateral
      side. No objective or subjective loss of normal deltoid appearance occurred.
      Rotator cuff repair did not compromise deltoid strength or significantly reduce
      ASES score irrespective of repair technique (arthroscopic vs mini-open). With
      careful attention to surgical technique maintaining an intact periosteal sleeve
      to preserve the integrity of the deltoid attachment, arthroscopic excision is an
      effective management tool for mobile os acromiale in a painful shoulder requiring
      surgical intervention.

PMID- 23127451
TI  - Plating of proximal humeral fractures.
AB  - The optimal treatment for proximal humeral fractures is controversial. Few data
      exist concerning the influence of the surgical approach on the outcome. The
      purpose of this study was to evaluate the clinical and radiological outcomes of
      proximal humeral fractures treated with locking plate fixation through a
      deltopectoral vs an anterolateral deltoid-splitting approach. Of 86 patients who
      met the inclusion criteria, 70 were available for follow-up examination. Thirty
      three patients were treated through a deltopectoral approach and 37 through an
      anterolateral deltoid-splitting approach. In all cases, open reduction and
      internal fixation with a PHILOS locking plate (Synthes, Umkirch, Germany) was
      performed. Clinical follow-up included evaluation of pain, shoulder mobility, and
      strength. Constant score and Disabilities of the Arm, Shoulder and Hand (DASH)
      score were assessed. A clinical neurological examination of the axillary nerve
      was also performed. Consolidation, reduction, and appearance of head necrosis
      were evaluated radiographically. After a mean follow-up of 33 months, Constant
      scores, DASH scores, and American Shoulder and Elbow Surgeons scores showed no
      significant differences between the groups. Clinical neurologic examination of
      the axillary nerve revealed no obvious damage to the nerve in either group.
      Deltopectoral and anterolateral detoid-splitting approaches for plate fixation of
      proximal humeral fractures are safe and provide similar clinical outcomes. The
      results of this study suggest that the approach can be chosen according to
      surgeon preference.

PMID- 23127452
TI  - Locking versus nonlocking palmar plate fixation of distal radius fractures.
AB  - This study compared functional and radiological outcomes after treatment of
      extension-type distal radius fractures with conventional titanium nonlocking T
      plates or titanium 1.5-mm locking plates. A total of 60 patients were included
      and followed for 4 to 7 years after receiving nonlocking T-plates (group A; n=30)
      or locking plates (group B; n=30) with and without dorsal bone grafting. Bone
      grafting was significantly more often performed in the nonlocking group to
      increase dorsal fracture fixation and stability (P<.003). Pre- and postoperative
      and follow-up values for palmar tilt, radial inclination, radial shortening, and
      ulnar variance were recorded. Age, sex, and fracture type were similarly
      distributed between the 2 groups. Postoperative and follow-up evaluation revealed
      equal allocation of intra-articular step formation and osteoarthritic changes to
      both groups. The overall complication rate was 25%. Compared with the nonlocking
      system, patients undergoing locking plate fixation presented with statistically
      significantly better values for postoperative palmar tilt (5.53 degrees  vs 8.15
      degrees ; P<.02) and radial inclination (22.13 degrees  vs 25.03 degrees ;
      P<.02). However, forearm pronation was significantly better in group A (P<.005).
      At follow-up, radial inclination tended to approach a statistically significant
      difference in favor of group B. All clinical assessment, including Mayo wrist
      score, Disabilities of the Arm, Shoulder, and Hand score, Green and O'Brien
      score, Gartland and Werley score, visual analog scale score, and grip strength,
      yielded no statistically significant difference between the 2 groups. Locking
      plates seem to provide benefits regarding surgical technique and comfort,
      improvement in implant anchorage (especially in osteoporotic bone), and reduce
      the necessity of additional bone grafting.

PMID- 23127453
TI  - Relationship between implant use, operative time, and costs associated with
      distal biceps tendon reattachment.
AB  - The suture anchor and transosseous drill hole techniques for reattachment of the
      distal biceps tendon to the radius have been found to have similar clinical and
      biomechanical outcomes. However, a comparison of the cost effectiveness of these
      techniques is lacking. The purpose of this study was to determine whether the use
      of suture anchors decreases operative time enough to offset the additional cost
      of the implants. The records of all patients undergoing a distal biceps tendon
      reattachment were reviewed to determine the method of fixation, operative time,
      and associated surgical costs. Two surgeons used a technique of fixing the tendon
      directly to the bone (transosseous group), whereas 3 surgeons used suture
      anchors. Given the standard nature of the surgical procedure (other than the
      fixation technique), only the costs that differed between the 2 groups were
      included. Surgical center costs were obtained from the local outpatient surgical
      center in 2011 US dollars. Five surgeons treated 70 men (mean age, 45.9+/-9.2
      years). Mean time from injury to surgery was 14 days. Mean operative times for
      the transosseous and suture anchor groups were 97.6+/-14.9 and 95.8+/-25.8
      minutes, respectively (P=.74). Two anchors were used in 79% of the anchor cases.
      The use of anchors cost $474.33 more per patient. However, this value is
      sensitive to the cost of the individual anchors, intersurgeon variation in
      operative time, and per-minute value of saved operative time. No operative time
      was saved with the use of suture anchors. This cost comparison framework can be
      used to evaluate the balance in surgical resource use due to implant cost vs
      savings in operative time.

PMID- 23127454
TI  - Distraction arthrolysis of posttraumatic elbow stiffness with a hinged external
      fixator.
AB  - The treatment of elbow stiffness remains a challenge for orthopedic surgeons. A
      hinged external fixator with distraction ability has recently emerged as a new
      option in the surgical treatment of elbow stiffness. Between January 2007 and
      December 2009, twenty-five posttraumatic stiff elbows (mean patient age, 29.2
      years) received distraction arthrolysis from 1 surgeon group (W.J.W., L.H.,
      P.Z.J.) at the authors' institution. For patients with only periarticular soft
      tissue contracture (grade 1), close mechanical distraction was performed with the
      assistance of an external fixator under anesthesia; open arthrolysis was avoided
      as much as possible. For patients who also had heterotopic ossification (grade
      2), it was removed through a limited approach before the external fixator was
      applied. For patients with osteoarticular surface damage or destruction (grade
      3), osteoarticular integrity was restored before arthrolysis. Range of motion
      increased markedly, from 33.4 degrees  (range, 0 degrees -75 degrees )
      preoperatively to 105.6 degrees  (range, 80 degrees -140 degrees ) immediately
      postoperatively (Student's t test, P<.05). Of the 25 patients, 23 were followed
      for a mean of 16 months. No serious complications occurred. Mean range of motion
      was 97.4 degrees  (range, 70 degrees -130 degrees ) at final follow-up, a
      significant increase from preoperatively (Student's t test, P<.05). No
      significant loss of range of motion was found at final follow-up compared with
      intraoperative values (average 8.2 degrees  loss; Student's t test, P>.05). This
      study suggests that a hinged external distraction fixator is a less invasive
      option for treating posttraumatic elbow stiffness and prevents contracture
      recurrence after arthrolysis.

PMID- 23127455
TI  - Open reduction and intramedullary nail fixation of closed tibial fractures.
AB  - Some tibial shaft fractures cannot be accurately reduced using closed or
      percutaneous techniques during an intramedullary nailing procedure. Under these
      circumstances, a formal open reduction can be performed. Direct exposure of the
      fracture facilitates accurate reduction but does violate the soft tissue
      envelope. The purpose of this study was to evaluate the safety and efficacy of
      open reduction prior to intramedullary nailing. Using the trauma database at a
      Level I trauma center, 11 uncomplicated closed displaced tibia fractures treated
      with formal open reduction prior to intramedullary nailing were identified and
      matched with a cohort of 21 fractures treated with closed reduction and nailing.
      The authors attempted to match 2 controls to each patient to improve the power of
      the study. Clinical and radiographic outcomes were compared. All fractures
      ultimately healed within 5 degrees  of anatomic alignment. No infections or non
      unions occurred in the open reduction group, and 1 deep infection and 1 nonunion
      occurred in the closed reduction group. No significant differences existed
      between the study groups. Although closed reduction and intramedullary nailing
      remains the treatment of choice for most significantly displaced tibial shaft
      fractures, open reduction with respectful handling of the soft tissue envelope
      can be safe and effective and should be considered when less invasive techniques
      are unsuccessful.

PMID- 23127456
TI  - Delineation of alar ligament morphology: comparison of magnetic resonance imaging
      at 1.5 and 3 Tesla.
AB  - Rupture of the alar and transverse ligaments due to whiplash injury can lead to
      upper cervical spine instability and subsequent neurological deterioration. The
      purpose of this study was to evaluate the normal anatomical variability of the
      alar ligaments in asymptomatic individuals with 3-T magnetic resonance imaging
      (MRI) and to compare the findings with standard 1.5-T examinations. Thirty-six
      participants underwent 3-T and 1.5-T MRIs. Magnetic resonance imaging findings
      were analyzed by classifying the alar ligaments with regard to the features
      detectability, signal intensity compared with muscle tissue, homogeneity, shape,
      spatial orientation, and symmetry. Delineation of the alar ligaments was
      significantly better on 3-T images, which were subjectively preferred for
      evaluation. The alar ligaments showed great variability. In the majority of
      participants, the alar ligaments were hypointense to muscle tissue,
      inhomogeneous, and different in shape and orientation. A statistically
      significantly higher number of ligaments appeared symmetric on 3-T imaging,
      indicating that 1.5-T imaging may underestimate the proportion of patients with
      normal, symmetric ligaments. This study demonstrates that high-field 3-T MRI
      provides better visualization of the alar ligaments compared with 1.5-T MRI. The
      higher signal-to-noise ratio allows detection of small signal changes. A great
      interindividual variety of the MRI morphology of the alar ligaments was found in
      participants with no history of neck trauma. Further studies with more
      participants are necessary to evaluate alar ligament pathologies in patients with
      a history of whiplash injury.

PMID- 23127457
TI  - Cocaine use and surgical outcomes of cervical spondylotic myelopathy: a
      retrospective study.
AB  - The purpose of this study was to determine the average age of individuals
      diagnosed with cervical spinal myelopathy who are known cocaine users vs
      nonusers, as well as the postoperative change in neurological condition between
      cocaine users and nonusers. Medical records of patients diagnosed with cervical
      spinal myelopathy between January 1990 and May 2006 were reviewed. Ninety-four
      patients were identified who underwent any surgical intervention with at least 2
      years of follow-up. Group 1 comprised patients with cervical spinal myelopathy
      who had used cocaine, and group 2 comprised patients with cervical spinal
      myelopathy who had not used cocaine. All patients were clinically evaluated by
      the Nurick grade preoperatively and at most recent follow-up. Mean follow-up was
      25 months. Mean age at presentation was 52 years (range, 44-62 years) in group 1
      and 56 years (range, 42-88 years) in group 2. Average duration of symptoms prior
      to surgical intervention was 18.6 months in group 1 and 10 months in group 2.
      Average Nurick grade at presentation was 2.7 for group 1 and 2.7 for group 2.
      Average postoperative Nurick grade was 1.9 for group 1 and 1.33 for group 2.
      Change in Nurick grade was 0.8 for group 1 and 1.11 for group 2. Linear
      regression analysis comparing change in Nurick grade (from pre- to postoperative)
      was conducted, showing a correlation of -0.45 with a P value of .044. To the
      authors' knowledge, this is the first study demonstrating that cocaine use has an
      effect on postoperative improvement of neurological function in cervical
      spondylotic myelopathy.

PMID- 23127458
TI  - Lower-extremity weight-bearing compliance is maintained over time after
      biofeedback training.
AB  - Previous studies have shown immediate compliance with weight-bearing instructions
      to be better after biofeedback training than after verbal or scale training. This
      study assessed retention of biofeedback training to determine potential clinical
      applicability. Twelve participants were enrolled in a prospective clinical study
      at an academic orthopedic center. Participants were trained with a biofeedback
      device to comply with touch-down weight-bearing instructions (25 lb). Immediately
      following the training session, weight bearing was assessed for each participant.
      The retention of this training was then reassessed at 2 to 4, 6 to 8, and 22 to
      24 hours. Two control participants were given no biofeedback training (verbal
      instructions only) and were followed similarly. Following initial biofeedback
      training at 25 lb, participants bore an average of 20.4+/-2.12 lb. Retention
      tests during the 24-hour period showed no significant difference from the
      original testing, with 2- to 4-hour retention of 19.98+/-4.75 lb, 6- to 8-hour
      retention of 25.07+/-6.60 lb, and 22- to 24-hour retention of 21.75+/-4.58 lb.
      Participants who only received verbal instructions consistently bore several-fold
      greater weight than instructed. Biofeedback training has previously been shown to
      have a strong immediate effect on partial weight-bearing compliance. This study
      demonstrated that this effect lasts up to 24 hours. This maintained weight
      bearing compliance after biofeedback training suggests that this method may be an
      effective way to train patients to comply with given instructions for limited
      weight bearing.

PMID- 23127459
TI  - Effect of work-hour restrictions and resident turnover in orthopedic trauma.
AB  - The resident 80-hour workweek and the July phenomenon have raised concern
      regarding the continuity of care of orthopedic patients in teaching institutions
      and its effect on postoperative complications and mortality. This study examined
      the effect of resident work-hour restrictions and the July phenomenon on patient
      outcomes after hip fracture at a large academic institution. Seven hundred twenty
      two patients (mean age, 76.7 years) sustaining 319 femoral neck fractures and 403
      intertrochanteric fractures between 2000 and 2010 were identified. Analysis was
      performed before and after July 1, 2003, as well as for the month of treatment.
      No difference existed in the postoperative outcome measures of delay of surgery
      (P=.061), complications (P=.904), and mortality (P=.981) between patients treated
      before and after July 1, 2003. Patients treated after July 1, 2003, had a
      significantly higher median number of preoperative comorbidities (4 vs 3,
      respectively; P<.0005). Turnover months, July and August, showed no difference in
      the outcome measures of delay of surgery (P=.171), complications (P=.776), and
      mortality (P=.524) compared with other months. This study suggests that 80-hour
      workweek restrictions or resident turnover months have no effect on patient care
      with respect to in-hospital time to surgery, complications, and mortality. This
      success can be attributed to ancillary staff support, physician extenders, and
      well-designed patient care protocols.

PMID- 23127460
TI  - Level of billing as a function of resident documentation and orthopedic
      subspecialty at an academic multispecialty orthopedic surgery practice.
AB  - Documentation, coding, and billing for physician-patient encounters have evolved
      over time and have significant variability. Appropriate and complete
      documentation of these encounters can contribute to the financial viability of
      private and academic medical centers. The objectives of this study were to assess
      the financial effect of documentation on billing and to compare the authors'
      institution's distribution of billing level compared with Medicare normative
      data. Four orthopedic surgery subspecialty clinics were evaluated at a university
      outpatient clinic over a 1-year period. A single full-day clinic per week was
      used for each subspecialty. Residents dictated the majority of the reports. All
      reports were transcribed by medical transcriptionists and coded by certified
      professional coders. The sports medicine subspecialty generated the highest
      volume of patient clinic visits, followed by foot and ankle, trauma, and spine
      (P<.01). The majority of the reports were billed at level 3 (P<.05). Significant
      differences existed between subspecialty and percentage distribution of billing
      level (P<.05). Compared with Medicare normative data, a significantly greater
      percentage of level 3 reports and a lower percentage of level 2 and 4 reports
      existed in the orthopedic practice (P<.01). The estimated loss of revenue from
      the fewer level 4 reports was $81,281.11 for 1 year. These findings highlight the
      need for greater educational interventions to improve provider documentation,
      coding, and billing. The effect of new electronic medical record systems that
      prompt providers to include key evaluation and management components will likely
      affect practices and warrant further analysis.

PMID- 23127461
TI  - Paradoxical cerebral embolism after total knee arthroplasty.
AB  - Deep vein thrombosis is a frequent complication following total joint
      arthroplasty and other major orthopedic procedures. Pulmonary embolism occurs
      with or without a diagnosis of deep vein thrombosis, although infrequently (1.5%
      10%). In patients with congenital cardiac defects, such as a patent foramen
      ovale, paradoxical cerebral embolism may also occur. This article describes a
      case of a 52-year-old woman who sustained a paradoxical cerebral embolism
      following total knee arthroplasty. In the workup of a patient with a known murmur
      and stroke symptoms, paradoxical cerebral embolism should be included in the
      differential. The initial evaluation should incorporate transesophageal
      echocardiography because of its accuracy in the demonstration of the cardiac
      physiology. An abnormal intracardiac or intrapulmonary shunt is essential for
      paradoxical cerebral embolism, allowing the entrance of the thrombus into
      cerebral circulation from the venous system. No clear consensus has been reached
      on the management of patients at risk for paradoxical cerebral embolism prior to
      orthopedic procedures. However, when an embolic stroke is diagnosed acutely,
      ideal management includes thrombolytic therapy, but further research is needed to
      confirm that this is the correct management. Due to the risk of recurrence,
      postoperative thromboprophylaxis is recommended with or without closure of the
      foramen ovale. Most importantly, and as demonstrated by the current patient, who
      partially recovered but did not require walking assistance after 2-year follow
      up, treating physicians should be prepared to counsel patients through a
      lengthened physical rehabilitative process.

PMID- 23127462
TI  - Total knee arthroplasty in a patient with skeletal fluorosis.
AB  - Published reports on patients with skeletal fluorosis undergoing total knee
      arthroplasty are rare. Skeletal fluorosis is a chronic condition that occurs
      secondary to the ingestion of food and water that contain high levels of
      fluoride. Although fluorosis may be described as osteosclerotic and marble-like
      in appearance, features may also include characteristics of osteomalacia and
      osteoporosis. This article describes the case of a 67-year-old man with skeletal
      fluorosis who underwent total knee arthroplasty complicated by fracture. An
      intramedullary guide was used for the proximal tibia and distal femoral bone cuts
      intraoperatively. Following the completion of the femoral bone cuts, it was noted
      that the drill used to open the femoral canal had breached the medial femoral
      cortex. Multiple fractures were seen in both femoral condyles. A revision femoral
      stem was chosen to complete the total knee arthroplasty but, after further
      manipulation of the femur, it appeared that the fracture had displaced. A LISS
      plate (Synthes, West Chester, Pennsylvania) was used to ensure fracture reduction
      and implant stability. The remainder of the procedure was completed without
      complication. One year postoperatively, functional knee range of motion was
      limited to 70 degrees  of flexion. Radiographs showed signs of healing and
      satisfactory implant position. This case highlights the importance of the
      preoperative examination and the need to fully appreciate the bone quality of
      patients prior to undertaking an orthopedic procedure. Variation from the use of
      intramedullary guides should be considered in patients with questionable bone
      quality undergoing total knee arthroplasty.

PMID- 23127463
TI  - Posttraumatic chronic patellar dislocation treated by distal femoral osteotomy
      and medial patellofemoral ligament reconstruction.
AB  - Chronic patellar dislocation is a rare condition where the patella remains
      dislocated throughout knee range of motion during flexion and extension. In
      adults, the delayed presentation of this condition is often due to symptoms
      caused by the onset of severe secondary osteoarthritis. To the authors'
      knowledge, all of the cases reported in the literature have been treated by
      patellofemoral or total knee replacements depending on patient age and the extent
      of the arthritis. This article describes a rare case of a 22-year-old woman who
      sustained a traumatic chronic patellar dislocation for 5 months. Clinical
      examination revealed a valgus deformity of the left leg secondary to childhood
      injury and that the patella lay lateral to the lateral femoral condyle throughout
      flexion and extension. Radiographs of the knee revealed patellar dislocation.
      Long-leg radiographs of the left leg showed an anatomic tibiofemoral angle of 17
      degrees  valgus. The anatomical (74 degrees ) and mechanical (80 degrees )
      lateral distal femoral angles were abnormal, whereas the medial proximal tibial
      angle (87 degrees ) was normal, confirming that the valgus deformity was due to
      the abnormal distal femur. The authors performed a distal femoral osteotomy to
      correct the valgus deformity. Medial patellofemoral ligament reconstruction using
      a hamstring autograft was performed to stabilize the patella.

PMID- 23127464
TI  - Pulmonary embolism after shoulder arthroscopy.
AB  - Deep venous thrombosis and pulmonary embolism events are common complications
      following lower-extremity orthopedic surgery. Conversely, deep venous thrombosis
      and pulmonary embolism events are rare following upper-extremity surgery,
      specifically shoulder arthroscopy. The purpose of this article is to emphasize
      the necessity of performing a thorough preoperative workup to uncover possible
      risk factors for deep venous thrombosis/pulmonary embolism despite the rare
      occurrence of developing a pulmonary embolism following shoulder arthroscopy.
      This article describes 3 patients who developed a nonfatal pulmonary embolism
      following elective shoulder arthroscopy. All 3 surgeries were performed with the
      patient in the lateral decubitus position. No complications were noted
      intraoperatively. Symptoms appeared at postoperative days 14, 29, and 2,
      respectively. One patient demonstrated no risk factors for developing a pulmonary
      embolism, whereas the other 2 exhibited risk factors for deep venous thrombosis
      and pulmonary embolism. Pulmonary embolism is a rare but serious complication
      following shoulder arthroscopy. Shoulder surgeons should be aware of the
      presenting signs and symptoms. Mechanical or chemical prophylaxis should be
      administered for patients with identified coagulopathic risk factors. Although it
      is rare for patients to develop a pulmonary embolism following upper-extremity
      shoulder arthroscopy, orthopedic surgeons must be aware of the possibility that a
      pulmonary embolism can occur after elective, uncomplicated shoulder arthroscopy.
      Surgeons should consider prophylactic measures for patients with identified
      coagulopathy disorders.

PMID- 23127465
TI  - Recurrent posterior shoulder instability after rifle shooting.
AB  - Rifle shooting produces a sudden counterforce against the body thorough the
      anterior shoulder, which may produce a traumatic injury in soldiers. Posterior
      instability of the shoulder can occur in soldiers who practice rifle shooting. To
      the authors' knowledge, few reports have examined shooting-related injuries in
      soldiers. This article describes the case of a 27-year-old male soldier who
      presented with left shoulder pain and instability after rifle training. He
      developed symptoms, and presented radiographic findings consistent with a
      posterior Bankart lesion. Intraoperatively, while in the lateral decubitus
      position, a posterior portal was created 3 cm inferior and 2 cm lateral to the
      posterolateral corner of acromion for making a proper angle for inserting
      anchors. A reverse bony Bankart lesion and adjacent cartilage breakdown at the
      glenoid rim were noted. An arthroscopic capsulolabral repair was performed with 3
      mm bioabsorbable anchors to the glenoid rim. No gross reverse Hill-Sachs lesion
      or hyaline cartilage lesion was noted. Postoperatively, the arm was supported in
      a sling with an abduction pillow for 5 weeks. Codman's exercises, scapular
      protraction exercises, and elbow and wrist exercises were started. Physical
      therapy focused on reestablishing glenohumeral range of motion and rotator cuff
      and periscapular muscle strength. Six months postoperatively, the patient had
      normal scapular kinesis and reported no shoulder pain or symptoms of instability
      associated with a reverse bony Bankart lesion.

PMID- 23127466
TI  - Ulnar nerve palsy associated with closed midshaft forearm fractures.
AB  - Ulnar nerve palsy is a rare complication of closed midshaft forearm fractures;
      only 8 cases have been reported. This article describes a case of ulnar nerve
      palsy associated with a midshaft forearm fracture. A 12-year-old girl sustained a
      right midshaft forearm fracture. Whether she had a peripheral nerve injury was
      unknown due to strong pain. She underwent emergency manual reduction and
      intramedullary pinning. However, ulnar nerve palsy was remarkable postoperatively
      and gradually worsened. Therefore, neurolysis was performed 9 weeks later. The
      nerve had adhered to surrounding scar tissue. Six months after a second surgery,
      she had no motor dysfunction. The pathogenesis of ulnar nerve palsy complicated
      with midshaft forearm fractures varies and may be the result of direct contusion,
      direct damage by a bony spike, bony entrapment after closed reduction, and
      entrapment by a scar. In the current case, the patient was uncooperative at
      initial examination. Therefore, it is unknown whether she presented with
      immediate ulnar nerve palsy after the fracture. However, the ulnar nerve was not
      entrapped at the fracture site, and the surrounding muscle was intact but adhered
      to the surrounding scar tissue. The etiology of this case was considered to be
      entrapment by scar formation. According to a literature search, the authors
      recommend exploring the nerve approximately 8 to 10 weeks after primary surgery,
      after which neurological symptoms do not tend to improve.

PMID- 23127467
TI  - beta-Site amyloid precursor protein-cleaving enzyme 1 activity is related to
      cerebrospinal fluid concentrations of sortilin-related receptor with A-type
      repeats, soluble amyloid precursor protein, and tau.
AB  - BACKGROUND: beta-Site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1)
      activity determines the rate of APP cleavage and is therefore the main driver of
      amyloid beta production, which is a pathological hallmark of Alzheimer's disease
      (AD). METHODS: The present study explored the correlation between BACE1 activity
      and cerebrospinal fluid (CSF) markers of APP metabolism and axonal degeneration
      in 63 patients with mild AD and 12 healthy control subjects. RESULTS: In the AD
      group, positive correlations between BACE1 activity and soluble APP beta, the APP
      sorting receptor sortilin-related receptor with A-type repeats (also known as
      SorLA or LR11), and tau were detected. BACE1 activity was not associated with
      amyloid beta1-42 or soluble APP alpha concentrations in the AD group, and no
      associations between BACE1 activity and any of the protein concentrations were
      found in the control group. CONCLUSION: Our results confirm the relevance of
      BACE1 and sortilin-related receptor with A-type repeats within the amyloid
      cascade and also provide a further piece of evidence for the link between amyloid
      and tau pathology in AD.

PMID- 23127468
TI  - Cognitive and functional resilience despite molecular evidence of Alzheimer's
      disease pathology.
AB  - BACKGROUND: The correlation between neuropathological lesions and cognition is
      modest. Some individuals remain cognitively intact despite the presence of
      significant Alzheimer's disease (AD) pathology, whereas others manifest cognitive
      symptoms and dementia in the same context. The aim of the present study was to
      examine cognitive and cerebral reserve factors associated with resilient
      functioning in the setting of AD pathology. METHODS: University of Pennsylvania
      Alzheimer's Disease Center research participants with biochemical biomarker
      evidence of AD pathology (cerebrospinal fluid amyloid-beta1-42 <192 pg/mL) and
      comparable medial temporal lobe atrophy were categorized by Clinical Dementia
      Rating Scale-Sum of Boxes (CDR-SOB) score as AD dementia (CDR-SOB >1) or AD
      resilient (CDR-SOB <=0.5). Groups were compared for a variety of demographic,
      clinical, and neuroimaging variables to identify factors that are associated with
      resilience to AD pathology. RESULTS: A univariate model identified education and
      intracranial volume (ICV) as significant covariates. In a multivariate model with
      backward selection procedure, ICV was retained as a factor most significantly
      associated with resilience. The interaction term between ICV and education was
      not significant, suggesting that larger cranial vault size is associated with
      resilience even in the absence of more education. CONCLUSIONS: Premorbid brain
      volume, as measured through ICV, provided protection against clinical
      manifestations of dementia despite evidence of significant accumulations of AD
      pathology. This finding provides support for the brain reserve hypothesis of
      resilience to AD.

PMID- 23127469
TI  - The ADAS-Cog revisited: novel composite scales based on ADAS-Cog to improve
      efficiency in MCI and early AD trials.
AB  - BACKGROUND: The Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) has
      been used widely as a cognitive end point in Alzheimer's Disease (AD) clinical
      trials. Efforts to treat AD pathology at earlier stages have also used ADAS-Cog,
      but failure in these trials can be difficult to interpret because the scale has
      well-known ceiling effects that limit its use in mild cognitive impairment (MCI)
      and early AD. A wealth of data exists in ADAS-Cog from both historical trials and
      contemporary longitudinal natural history studies that can provide insights about
      parts of the scale that may be better suited for MCI and early AD trials.
      METHODS: Using Alzheimer's Disease Neuroimaging Initiative study data, we
      identified the most informative cognitive measures from the ADAS-Cog and other
      available scales. We used cross-sectional analyses to characterize trajectories
      of ADAS-Cog and its individual subscales, as well as other cognitive, functional,
      or global measures across disease stages. Informative measures were identified
      based on standardized mean of 2-year change from baseline and were combined into
      novel composite endpoints. We assessed performance of the novel endpoints based
      on sample size requirements for a 2-year clinical trial. A bootstrap validation
      procedure was also undertaken to assess the reproducibility of the standardized
      mean changes of the selected measures and the corresponding composites. RESULTS:
      All proposed novel endpoints have improved standardized mean changes and thus
      improved statistical power compared with the ADAS-Cog 11. Further improvements
      were achieved by using cognitive-functional composites. Combining the novel
      composites with an enrichment strategy based on cerebral spinal fluid beta
      amyloid (Abeta(1-42)) in a 2-year trial yielded gains in power of 20% to 40% over
      ADAS-Cog 11, regardless of the novel measure considered. CONCLUSION: An
      empirical, data-driven approach with existing instruments was used to derive
      novel composite scales based on ADAS-Cog 11 with improved performance
      characteristics for MCI and early AD clinical trials. Together with patient
      enrichment based on Abeta(1-42) pathology, these modified endpoints may allow
      more efficient clinical trials in these populations and can be assessed without
      modifying current test administration procedures in ongoing trials.

PMID- 23127471
TI  - A simple skin-graft dressing method with surgical gloves.

PMID- 23127472
TI  - Favorable long-term outcomes in patients with histologically dysplastic nevi that
      approach a specimen border.
AB  - BACKGROUND: Patients with multiple clinically dysplastic nevi are at increased
      risk for development of melanoma. However, the risk of melanoma arising in a
      histologically dysplastic nevus (HDN) is unknown. OBJECTIVE: We sought to
      determine the rate of melanoma development in patients with HDNs that approached
      a microscopic border but were not re-excised. METHODS: We performed a
      retrospective study of patients evaluated in our dermatology department from
      January 1, 1980, to December 31, 1989, who had a HDN that extended to within 0.2
      mm of a microscopic punch, shave, or excision border and was not re-excised.
      RESULTS: The average follow-up in our cohort of 115 patients was 17.4 years
      (range: 0.0-29.9): 82 patients (71.3%) were followed up for longer than 10 years,
      78 (67.8%) longer than 15 years, and 73 (63.4%) had more than 20 years of follow
      up; 66 of 115 nevi were mildly dysplastic, 42 moderately dysplastic, and 7 had
      severe dysplasia. No patient developed metastatic melanoma or melanoma at the
      site of removal of a HDN. LIMITATIONS: This was a retrospective study performed
      at 1 large academic medical center. CONCLUSION: During a long-term follow-up
      period, no patient developed melanoma at the site of an incompletely or narrowly
      removed HDN, providing evidence that routine re-excision of mildly or moderately
      dysplastic nevi may not be necessary.

PMID- 23127473
TI  - Positron emission tomography/computed tomography imaging in Merkel cell
      carcinoma: a study of 270 scans in 97 patients at the Dana-Farber/Brigham and
      Women's Cancer Center.
AB  - BACKGROUND: Merkel cell carcinoma (MCC) is a rare and lethal cutaneous
      neuroendocrine carcinoma. Imaging is crucial for accurate staging, which remains
      a strong predictor of survival, as well as earlier detection of recurrence and
      progression, which are common despite aggressive management. There is no
      consensus on the role of initial and subsequent imaging for MCC. OBJECTIVE: We
      sought to evaluate the use of 2-fluoro-[(18)F]-deoxy-2-D-glucose (FDG)-positron
      emission tomography (PET)/computed tomography (CT) in the management of MCC.
      METHODS: In all, 270 FDG-PET/CT studies were performed in 97 patients with
      pathology-proven MCC at the Dana-Farber/Brigham and Women's Cancer Center,
      Boston, Mass, from August 2003 to December 2010. RESULTS: FDG-PET/CT scans were
      obtained as part of the initial (61 scans in 61 patients) and subsequent (209
      scans in 79 patients) treatment strategies. MCCs were FDG-avid with a mean
      maximum standardized uptake value of primary lesions of 6.5 (range 1.3-12.9) and
      a mean maximum standardized uptake value of regional and distant metastases of
      7.2 (range 1.5-9.9). FDG-PET/CT upstaged 16% of patients who underwent baseline
      scans. FDG-PET/CT studies showed that bone and bone-marrow metastases were more
      common than previously reported, and were often undetected by CT. LIMITATIONS:
      Our study is limited by its retrospective design, and potential referral bias
      associated with a tertiary care center. CONCLUSIONS: FDG-PET/CT performed as part
      of the initial management strategy tended to upstage patients with more advanced
      disease. FDG-PET/CT performed as part of the subsequent treatment strategy
      identified metastatic disease, particularly in bone/bone marrow, which was not
      seen on CT. FDG-PET/CT imaging is a valuable staging and restaging tool in MCC
      management.

PMID- 23127474
TI  - Speed-accuracy trade-off in skilled typewriting: decomposing the contributions of
      hierarchical control loops.
AB  - Typing performance involves hierarchically structured control systems: At the
      higher level, an outer loop generates a word or a series of words to be typed; at
      the lower level, an inner loop activates the keystrokes comprising the word in
      parallel and executes them in the correct order. The present experiments examined
      contributions of the outer- and inner-loop processes to the control of speed and
      accuracy in typewriting. Experiments 1 and 2 involved discontinuous typing of
      single words, and Experiments 3 and 4 involved continuous typing of paragraphs.
      Across experiments, typists were able to trade speed for accuracy but were unable
      to type at rates faster than 100 ms/keystroke, implying limits to the flexibility
      of the underlying processes. The analyses of the component latencies and errors
      indicated that the majority of the trade-offs were due to inner-loop processing.
      The contribution of outer-loop processing to the trade-offs was small, but it
      resulted in large costs in error rate. Implications for strategic control of
      automatic processes are discussed.

PMID- 23127475
TI  - Timing and executive resources: dual-task interference patterns between temporal
      production and shifting, updating, and inhibition tasks.
AB  - Three dual-task experiments were designed to assess the contribution of executive
      cognitive functions to the perception of time. Each experiment combined a serial
      temporal production timing task with an executive task emphasizing either
      shifting, updating, or inhibition. The experiments uncovered evidence of
      bidirectional interference between the concurrent tasks, such that the executive
      tasks interfered with timing performance and the timing task interfered with
      executive performance. Each experiment also included 3 dual-task conditions in
      which subjects allocated attention to the concurrent tasks in specified
      proportions. The results showed a reciprocal tradeoff in performance on each
      task: More attention allocated to timing caused timing performance to improve and
      executive performance to decline, whereas more attention allocated to the
      executive task produced the opposite pattern. The findings suggest that timing
      relies on the same processing resources that support basic executive functions.

PMID- 23127476
TI  - Divergent effects of cognitive load on quiet stance and task-linked postural
      coordination.
AB  - Performing a cognitive task while maintaining upright stance can lead to
      increased or reduced body sway depending on tasks and experimental conditions.
      Because greater sway is commonly taken to indicate loosened postural control, and
      vice versa, the precise impact of cognitive load on postural stability has
      remained unclear. In much of the large literature on posture-cognition dual
      tasking, the assigned postural task is to simply maintain stance (so-called
      "quiet standing"). This contrasts with quotidian use of postural coordination to
      maintain balance while also facilitating suprapostural sensorimotor tasks. In
      this study, healthy young participants either maintained quiet stance or carried
      out a visuopostural alignment task while performing a spatial, nonspatial, or no
      additional cognitive task. Body sway increased during both cognitive tasks while
      quiet standing, as is often observed, but not while performing the visuopostural
      alignment task. This result is not consistent with the commonly invoked
      competition between tasks for limited processing resources. It suggests that
      constraints placed on posture control by suprapostural task goals may
      significantly alter interactions between posture control and cognitive tasks, and
      that dual-task results obtained under quiet standing conditions may not
      generalize to postural control in everyday task conditions.

PMID- 23127477
TI  - Clinical Dementia Rating independently predicted conversion to dementia in a
      cohort of urban elderly in Brazil.
AB  - BACKGROUND: Dementia is a major public health problem in aging populations. The
      Clinical Dementia Rating (CDR) classifies the severity of dementia and identifies
      borderline cases that supposedly have higher rates of conversion to dementia.
      This study aims to verify the dementia conversion rate (CR) in a subsample of an
      elderly cohort (70+ free of the disease), and to identify risk factors,
      determining whether CDR is able to predict which individuals have high likelihood
      of converting. METHODS: A subsample of 156 participants was clinically evaluated
      for dementia at baseline in which 80 patients without dementia were reassessed
      after 2.6 years on average to verify the conversion. The CR was analyzed
      according to demographic, health variables, and CDR classification at baseline,
      using the Poisson regression method in univariate and multivariate analyses, with
      exposure time as an offset variable (person-years). RESULTS: From those re
      evaluated, 50% had CDR = 0 and a CR of 38.1/1,000 person-years and the other 50%,
      CDR = 0.5 (70% with sum of boxes scores <=1, CR = 145.4/1,000 person-years and
      30% > 1, CR = 216.8/1,000 person-years). CR was 91.3/1,000 person-years on
      average. In the multivariate analysis, when compared with those with CDR = 0, the
      hazard ratio of those with CDR = 0.5 was 3.82; and for those with CDR = 0.5 and
      sum of boxes scores >1, 5.69. CONCLUSIONS: Conversion rate to dementia was
      significantly higher among those with CDR = 0.5 and even higher for those whose
      sum of boxes scores was >1. Therefore, CDR was able to predict which individuals
      had a higher likelihood of converting to dementia.

PMID- 23127478
TI  - Trait and state aspects of internal and external performance monitoring in
      schizophrenia.
AB  - Disturbed internal performance monitoring has been repeatedly demonstrated in
      schizophrenia. Along with internal monitoring, efficiently processing external
      task-relevant performance feedback that goes unnoticed by the internal monitoring
      system is crucial for adequate performance. It is unknown whether external
      monitoring is disturbed in schizophrenia and whether it is trait or state
      dependent. The current study investigated the effects of treatment on both
      internal and external performance monitoring in schizophrenia. Twelve
      schizophrenia patients and twelve matched healthy controls performed a modified
      flanker task while ERPs and behavioral measures were obtained. Both groups were
      assessed twice, with a six-week interval, during which the patients received
      antipsychotic treatment. Internal monitoring was investigated by means of the
      response-locked error-related negativity (Ne/ERN), an event-related potential
      component elicited by erroneous responses. External monitoring was investigated
      by analyzing the feedback-locked P300 elicited by task-relevant external response
      time feedback (late feedback). Compared to controls, schizophrenia patients
      showed diminished Ne/ERN amplitudes, which were insensitive to six weeks of
      treatment. Patients also had reduced P300 amplitudes in response to late feedback
      at the first assessment, but these were normalized at the second assessment.
      Also, patients showed increased performance following negative external feedback
      at the second session. This study demonstrates the importance of considering both
      forms of performance monitoring in schizophrenia. Diminished internal error
      processing seems to be an important 'trait' marker of the disorder, while
      processing of externally presented feedback appears to have a 'state' character,
      susceptible to treatment at both a neurophysiological and a behavioral level.

PMID- 23127479
TI  - Chlorhexidine-impregnated PEM/THFM polymer exhibits superior activity to
      fluconazole-impregnated polymer against Candida albicans biofilm formation.
AB  - Biofilm-associated infections represent a major challenge for biomaterials.
      Methods to alter the chemical characteristics of biomaterials offer an attractive
      solution for enhanced microbial control. The aim of this study was to investigate
      the efficacy of a poly(ethyl methacrylate)/tetrahydrofurfuryl methacrylate
      (PEM/THFM) acrylic model impregnated with fluconazole (FLU) or chlorhexidine
      (CHX) in preventing Candida biofilm formation in vitro. PEM/THFM disks
      impregnated with CHX (n=50) or FLU (n=50) and drug-free control disks (n=50) were
      infected with Candida albicans ATCC 90028. Disks were incubated for 2, 7, 14, 21
      or 28 days at 37  degrees C and the biofilm biomass and metabolic activity was
      quantified at each time point using crystal violet staining and XTT [2,3-bis(2
      methoxy-4-nitro-5-sulfo-phenyl)-2H-tetrazolium-5-carboxanilide] reduction assay.
      FLU disks exhibited poor overall biofilm inhibitory characteristics, with mean
      metabolic and biomass inhibition of 12.6% and 8.8%, respectively. Conversely, CHX
      disks were highly effective, significantly inhibiting biofilm development by 75%
      (P <= 0.001) and its metabolism by 84% (P <= 0.001) for all time points tested.
      The notable efficacy of CHX against C. albicans biofilms is a promising outcome
      to overcome the side effects and poor relative activity of conventional
      antifungal agents against Candida biofilms. These findings indicate that
      impregnation of PEM/THFM with antimicrobials has potential as a treatment
      modality for denture stomatitis.

PMID- 23127480
TI  - Salmonella enterica serotype Bovismorbificans, a new host for CTX-M-9.

PMID- 23127481
TI  - Characterisation of CTX-M-117, a Pro174Gln variant of CTX-M-15 extended-spectrum
      beta-lactamase, from a bovine Escherichia coli isolate.

PMID- 23127482
TI  - Understanding physician antibiotic prescribing behaviour: a systematic review of
      qualitative studies.
AB  - Inappropriate prescription has been associated with mounting rates of antibiotic
      resistance worldwide, demanding more detailed studies into physicians' decision
      making process. Accordingly, this study sought to explore physicians' perceptions
      of factors influencing antibiotic prescribing. A systematic search was performed
      for qualitative studies focused on understanding physicians' perceptions of the
      factors, attitudes and knowledge influencing antibiotic prescription. Of the
      total of 35 papers selected for review purposes, 18 solely included physicians
      and the remaining 17 also included patients and/or other healthcare providers.
      Data collection was based mainly on interviews, followed by questionnaires and
      focus groups, and the methodologies mainly used for data analysis were grounded
      theory and thematic analysis. Factors cited by physicians as having an impact on
      antibiotic prescribing were grouped into those that were intrinsic (group 1) and
      those that were extrinsic (group 2) to the healthcare professional. Among the
      former, physicians' attitudes, such as complacency or fear, were rated as being
      most influential on antibiotic prescribing, whilst patient-related factors (e.g.
      signs and symptoms) or healthcare system-related factors (e.g. time pressure and
      policies/guidelines implemented) were the most commonly reported extrinsic
      factors. These findings revealed that: (i) antibiotic prescribing is a complex
      process influenced by factors affecting all the actors involved, including
      physicians, other healthcare providers, healthcare system, patients and the
      general public; and (ii) such factors are mutually dependent. Hence, by shedding
      new light on the process, these findings will hopefully contribute to generating
      new and more effective strategies for improving antibiotic prescribing and
      allaying global concern about antibiotic resistance.

PMID- 23127483
TI  - First report of bla(PER-3) in Acinetobacter baumannii.

PMID- 23127484
TI  - Pharmacodynamic profiling of doripenem, imipenem and meropenem against prevalent
      Gram-negative organisms in the Asia-Pacific region.
AB  - Carbapenems are increasingly being utilised owing to the escalating prevalence of
      antimicrobial-resistant Gram-negative bacteria from community and hospital
      settings. In this study, pharmacodynamic profiles of doripenem, imipenem and
      meropenem were evaluated against Gram-negative bacteria isolated from
      hospitalised patients. MICs for carbapenems were determined for Escherichia coli,
      Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii
      obtained from the COMPACT II programme conducted in the Asia-Pacific region.
      Monte Carlo simulations were undertaken to assess the pharmacodynamic profile of
      carbapenems against each of the pathogens. All carbapenem regimens achieved
      optimal exposures [cumulative fraction of response (CFR) >=90%] against E. coli
      and K. pneumoniae. Against P. aeruginosa, doripenem achieved 81.3-95.3% CFR,
      imipenem achieved 55.2-77.9% CFR and meropenem achieved 71.9-91.3% CFR; only
      doripenem regimens of 4-h infusion of 1000 mg every 8h (q8h) and 1-h and 4-h
      infusion of 2000 mg q8h and a meropenem regimen of 3-h infusion of 2000 mg q8h
      obtained optimal exposures; all carbapenem regimens showed slight (1-7%)
      improvement in CFRs in favour of isolates collected from ICU sources. Against A.
      baumannii, CFRs were much lower (25.9-46.7% CFR) and no carbapenem regimens
      achieved optimal exposure in or outside the ICU. Owing to the high potency of
      carbapenems against these Enterobacteriaceae populations, standard regimens are
      likely to perform well in the Asia-Pacific region. However, larger doses combined
      with prolonged infusions will be required to increase the CFR for these
      carbapenems against resistant non-fermenting Gram-negatives such as P. aeruginosa
      and A. baumannii that are prevalent in these countries.

PMID- 23127485
TI  - The emergence of clinical resistance to tigecycline.
AB  - Tigecycline (TIG) exhibits broad-spectrum activity against many Gram-positive and
      Gram-negative pathogens. However, clinical resistance has emerged recently and
      has been detected following treatment with TIG. This observation suggests that
      long-term monotherapy may carry a high risk for TIG resistance. TIG resistance is
      observed most frequently in Acinetobacter baumannii and Enterobacteriaceae,
      especially in multidrug-resistant strains. Resistance-nodulation-cell division
      (RND)-type transporters and other efflux pumps may be factors for decreased
      sensitivity to TIG. Therefore, TIG should be cautiously used in the clinic, and
      efflux-mediated resistance should be closely monitored in order to prolong the
      lifespan of this useful antibiotic.

PMID- 23127486
TI  - Global evolution of multidrug-resistant Acinetobacter baumannii clonal lineages.
AB  - The rapid expansion of Acinetobacter baumannii clinical isolates exhibiting
      resistance to carbapenems and most or all available antibiotics during the last
      decade is a worrying evolution. The apparent predominance of a few successful
      multidrug-resistant lineages worldwide underlines the importance of elucidating
      the mode of spread and the epidemiology of A. baumannii isolates in single
      hospitals, at a country-wide level and on a global scale. The evolutionary
      advantage of the dominant clonal lineages relies on the capability of the A.
      baumannii pangenome to incorporate resistance determinants. In particular, the
      simultaneous presence of divergent strains of the international clone II and
      their increasing prevalence in international hospitals further support the
      ongoing adaptation of this lineage to the hospital environment. Indeed, genomic
      and genetic studies have elucidated the role of mobile genetic elements in the
      transfer of antibiotic resistance genes and substantiate the rate of genetic
      alterations associated with acquisition in A. baumannii of various resistance
      genes, including OXA- and metallo-beta-lactamase-type carbapenemase genes. The
      significance of single nucleotide polymorphisms and transposon mutagenesis in the
      evolution of A. baumannii has been also documented. Establishment of a network of
      reference laboratories in different countries would generate a more complete
      picture and a fuller understanding of the importance of high-risk A. baumannii
      clones in the international dissemination of antibiotic resistance.

PMID- 23127487
TI  - Phase I clinical trial of the novel platin complex dicycloplatin: clinical and
      pharmacokinetic results.
AB  - TRANSLATIONAL RELEVANCE: Dicycloplatin (DCP) is a novel super molecule composed
      of carboplatin (CBP) and 1,1-cyclobutane dicarboxylate (CBDCA) joined by a strong
      hydrogen bond. The solubility and stability of platinum complexes have a direct
      bearing on their activity, toxicity and pharmacokinetics. Preclinical studies
      have shown that DCP overcomes the problem of CBP instability in aqueous solution
      and maintains anticancer effects. Clinical evaluation in a Phase I dose
      escalation study in patients with tumors showed that DCP was tolerated at doses
      ranging from 100 to 550 mg/m(2) and had potential efficacy in Chinese cancer
      patients. DCP showed favourable bioavailability and stability in vivo, and the
      recommended Phase II dosage for DCP-containing chemotherapy is 450 mg/m(2). DCP
      is currently being investigated as a monotherapy in several cancer types, such as
      prostatic carcinoma, and in combination with paclitaxel in a Phase II non-lung
      cancer study. PURPOSE: Dicycloplatin (DCP) is a novel supramolecule composed of
      carboplatin (CBP) and 1,1-cyclobutane dicarboxylate (CBDCA) joined by a strong
      hydrogen bond. DCP is stable in aqueous solution unlike CBP alone. The purpose of
      this study was to assess the maximally tolerated dose, safety, and
      pharmacokinetics of DCP in Chinese cancer patients. EXPERIMENTAL DESIGN: 29
      patients were included in this study. DCP was administered by intravenous
      infusion over 1 hour once every 21 days. The dose of DCP was escalated from 50
      mg/m(2) to 650 mg/m(2) using a modified Fibonacci scheme. Pharmacokinetic
      analysis was performed in 26 patients to determine the total and ultrafiltered
      platinum concentrations in plasma. RESULTS: 29 and 20 patients were evaluated for
      toxicities and response, respectively. The primary adverse effects were
      nausea/vomiting (58.6%), thrombocytopenia (24.1%), neutropenia (17.2%), anemia
      (20.7%), fatigue (10.3%), anorexia (10.3%), liver enzyme elevation (10.3%) and
      alopecia (3.5%). There was no significant toxicity with doses up to 350 mg/m(2).
      At higher doses, a variety of dose-limiting toxicities (DLTs) were observed,
      including Grade 3/4 anemia, Grade 3/4 thrombocytopenia, and Grade 3/4 emesis
      under antiemetic treatment. The maximum tolerated dose of DCP was 550 mg/m(2).
      Two partial responses occurred in patients with non-cell lung cancer who had
      received cisplatin- or carboplatin-based chemotherapy. Plasma decay of total and
      free platinum concentrations was best fitted by using a twocompartment analysis.
      The terminal plasma half-life of total platinum after DCP administration ranged
      from 41.86 to 77.20 hours without significant dose dependency. However, the
      terminal plasma half-life of free platinum concentrations ranged from 42.34 to
      61.07 hours. CONCLUSIONS: DCP displayed a favorable safety profile at doses
      between 50 mg/m(2) and 550 mg/m(2), and first efficacy signals were observed.
      DLTs were thrombocytopenia, anemia and emesis. The recommended starting dose for
      a subsequent Phase II study is 450 mg/m(2) once every 3 weeks.

PMID- 23127488
TI  - Regulation of antigen transport into the cytosol for cross-presentation by
      ubiquitination of the mannose receptor.
AB  - The molecular mechanisms governing cross-presentation of extracellular antigens
      on MHC I molecules are not fully understood. It is generally assumed that, in
      order to be processed for cross-presentation, most antigens need to be
      transported from the endosomal compartment into the cytosol to be processed by
      the cytosolic proteasome. The mechanisms regulating such intracellular transport
      are largely unknown. In a recent study, we demonstrated that the ubiquitination
      status of the mannose receptor (MR), an endocytic receptor that targets its
      ligands specifically toward cross-presentation, can regulate such antigen export
      into the cytosol. Poly-ubiquitination of the MR recruits p97 toward the endosomal
      membrane, which is essential for antigen translocation out of the endosomes.
      Furthermore, we identified Tumor Susceptibility Gene 101 (TSG101) as an important
      regulator of MR poly-ubiquitination and hence of antigen translocation and cross
      presentation. Additionally, we describe in this article some perspectives and
      open questions regarding the molecular mechanisms of cross-presentation. In
      particular, we highlight the search for proteins regulating antigen translocation
      in the cytosol, the recruitment of ER proteins and proteasomes toward antigen
      containing endosomes and the importance of antigen stability for cross
      presentation.

PMID- 23127489
TI  - Diverse antigen presentation by the Group 1 CD1 molecule, CD1c.
AB  - CD1 molecules are Major Histocompatibility Complex (MHC) class I-like proteins
      that present diverse lipid antigens to T cells. Most of our understanding of CD1
      lipid presentation and T cell recognition has come from study of the invariant
      Natural Killer T cell recognition of CD1d. However, in addition to CD1d, humans
      possess three additional CD1 molecules: CD1a, CD1b and CD1c, referred to as the
      Group 1 CD1s. The lack of an appropriate murine molecule to probe the function
      and disease relevance of these molecules has hindered understanding their precise
      immunological role, despite their pivotal role in human immunity. In this
      perspective, we discuss the progress of functional and molecular studies of CD1c.
      CD1c has been shown to specifically present lipids from Mycobacterium
      tuberculosis and other related pathogenic mycobacteria. alphabeta T cells
      reactive to these lipids presented in the context of CD1c have been characterized
      and upon stimulation secrete IFN-gamma, an important cytokine in tuberculosis
      disease clearance. Other ligands characterized for CD1c include PI and PC, a
      lipopeptide with a dodecameric peptide moiety and sulfatides. These structurally
      and chemically diverse ligands suggest that CD1c has the capacity to present a
      wide repertoire of antigens to reactive T cells. Indeed, a substantial percentage
      (~2%) of the circulating alphabeta T cell population is reactive to CD1c
      presenting endogenous antigens, suggesting that this particular Group 1 molecule
      may play an important role in the human immune response.

PMID- 23127490
TI  - 3-Phenyl substituted 6,7-dimethoxyisoquinoline derivatives as FtsZ-targeting
      antibacterial agents.
AB  - The emergence of multidrug-resistant bacteria has created an urgent need for
      antibiotics with a novel mechanism of action. The bacterial cell division protein
      FtsZ is an attractive target for the development of novel antibiotics. The
      benzo[c]phenanthridinium sanguinarine and the dibenzo[a,g]quinolizin-7-ium
      berberine are two structurally similar plant alkaloids that alter FtsZ function.
      The presence of a hydrophobic functionality at either the 1-position of 5
      methylbenzo[c]phenanthridinium derivatives or the 2-position of
      dibenzo[a,g]quinolizin-7-ium derivatives is associated with significantly
      enhanced antibacterial activity. 3-Phenylisoquinoline represents a subunit within
      the ring-systems of both of these alkaloids. Several 3-phenylisoquinolines and 3
      phenylisoquinolinium derivatives have been synthesized and evaluated for
      antibacterial activity against Staphylococcus aureus and Enterococcus faecalis,
      including multidrug-resistant strains of methicillin-resistant S. aureus (MRSA)
      and vancomycin-resistant E. faecalis (VRE). A number of derivatives were found to
      have activity against both MRSA and VRE. The binding of select compounds to S.
      aureus FtsZ (SaFtsZ) was demonstrated and characterized using fluorescence
      spectroscopy. In addition, the compounds were shown to act as stabilizers of
      SaFtsZ polymers and concomitant inhibitors of SaFtsZ GTPase activity.
      Toxicological assessment of select compounds revealed minimal cross-reaction
      mammalian beta-tubulin as well as little or no human cytotoxicity.

PMID- 23127491
TI  - Halogenated pentamethine cyanine dyes exhibiting high fidelity for G-quadruplex
      DNA.
AB  - Design and optimization of quadruplex-specific small molecules is developing into
      an attractive strategy for anti-cancer therapeutics with some promising
      candidates in clinical trials. A number of therapeutically favorable features of
      cyanine molecules can be effectively exploited to develop them as promising
      quadruplex-targeting agents. Herein, the design, synthesis and evaluation of a
      series of dimethylindolenine cyanine dyes with varying halogen substitutions are
      reported. Their interactions with telomeric and c-myc quadruplexes as well as a
      reference duplex sequence have been evaluated using thermal melting, biosensor
      surface plasmon resonance, circular dichroism, isothermal titration calorimetry
      and mass spectrometry. Thermal melting analysis indicates that these ligands
      exhibit significant quadruplex stabilization and a very low duplex binding, with
      the dimethyl incorporation of paramount importance for decreased duplex affinity.
      Circular dichroism studies showed that the interaction of cyanines with
      quadruplex structures are primarily through stacking at one or both ends of the
      terminal tetrads with the two (trimethylammonium)propyl groups interacting in the
      accessible quadruplex grooves. Surface plasmon resonance and mass spectral
      studies shows the formation of an initial strong 1:1 complex followed by a
      significantly weaker secondary binding. Isothermal calorimetry studies show that
      the interaction of cyanines is predominantly entropy driven. In line with the
      design principles, this work provides new insights for further developing potent,
      highly selective cyanines as promising quadruplex-specific agents.

PMID- 23127492
TI  - Indoor tetrachloroethylene levels and determinants in Paris dwellings.
AB  - There is growing public health concern about indoor air quality.
      Tetrachloroethylene (PERC), a chlorinated volatile organic compound widely used
      as a solvent in dry cleaning facilities, can be a residential indoor air
      pollutant. As part of an environmental investigation included in the PARIS
      (Pollution and asthma Risk: an Infant Study) birth cohort, this study firstly
      aimed to document domestic PERC levels, and then to identify the factors
      influencing these levels using standardized questionnaires about housing
      characteristics and living conditions. Air samples were collected in the child's
      bedroom over one week using passive devices when infants were 1, 6, 9, and 12
      months. PERC was identified and quantified by gas chromatography/mass
      spectrometry. PERC annual domestic level was calculated by averaging seasonal
      levels. PERC was omnipresent indoors, annual levels ranged from 0.6 to 124.2
      MUg/m3. Multivariate linear and logistic regression models showed that proximity
      to dry cleaning facilities, do-it-yourself activities (e.g.: photographic
      development, silverware), presence of air vents, and building construction date
      (<1945) were responsible for higher domestic levels of PERC. This study,
      conducted in an urban context, provides helpful information on PERC contamination
      in dwellings, and identifies parameters influencing this contamination.

PMID- 23127493
TI  - Birth defects and environmental exposures: logical, diabolical or the devil is in
      the details?

PMID- 23127494
TI  - Seasonal concentrations and determinants of indoor particulate matter in a low
      income community in Dhaka, Bangladesh.
AB  - Indoor exposure to particulate matter (PM) increases the risk of acute lower
      respiratory tract infections, which are the leading cause of death in young
      children in Bangladesh. Few studies, however, have measured children's exposures
      to indoor PM over time. The World Health Organization recommends that daily
      indoor concentrations of PM less than 2.5MUm in diameter (PM(2.5)) not exceed
      25MUg/m(3). This study aimed to describe the seasonal variation and determinants
      of concentrations of indoor PM(2.5) in a low-income community in urban Dhaka,
      Bangladesh. PM(2.5) was measured in homes monthly during May 2009 to April 2010.
      We calculated the time-weighted average, 90th percentile PM(2.5) concentrations
      and the daily hours PM(2.5) exceeded 100MUg/m(3). Linear regression models were
      used to estimate the associations between fuel use, ventilation, indoor smoking,
      and season to each metric describing indoor PM(2.5) concentrations. Time-weighted
      average PM(2.5) concentrations were 190MUg/m(3) (95% CI 170-210). Sixteen percent
      of 258 households primarily used biomass fuels for cooking and PM(2.5)
      concentrations in these homes had average concentrations 75MUg/m(3) (95% CI 56
      124) greater than other homes. PM(2.5) concentrations were also associated with
      burning both biomass and kerosene, indoor smoking, and ventilation, and were more
      than twice as high during winter than during other seasons. Young children in
      this community are exposed to indoor PM(2.5) concentrations 7 times greater than
      those recommended by World Health Organization guidelines. Interventions to
      reduce biomass burning could result in a daily reduction of 75MUg/m(3) (40%) in
      time-weighted average PM(2.5) concentrations.

PMID- 23127495
TI  - Relocalization of KIT D816V to cell surface after dasatinib treatment: potential
      clinical implications.
AB  - BACKGROUND: Systemic mastocytosis (SM) is a heterogeneous disease that displays
      variable aggressivity. Adults with SM frequently have a D816V mutation in the
      tyrosine kinase (TK) receptor gene KIT. We previously reported that, in a Chinese
      hamster ovarian cell model expressing exogenous KIT variants, constitutive
      activating KIT mutations induced intracellular mislocalization of KIT reversed by
      inhibition of KIT TK activity. Hence, we hypothesized that inhibition of KIT
      kinase activity by the TK inhibitor dasatinib could be useful to increase KIT
      detection sensitivity in samples from patients with SM. PATIENTS AND METHODS: We
      tested this hypothesis on a BaF/3 cell line modified to express either KIT wild
      type (WT) or KIT D816V, on the human mastocytoma cell line HMC1.2, and among 28
      patients with proven SM who did (n = 24) or did not (n = 4) carry the D816V KIT
      mutation and displayed various SM subtypes by using a simple flow cytometry assay
      to quantify KIT relocalization upon dasatinib treatment. RESULTS: We confirm KIT
      cell surface increase upon dasatinib treatment on BaF/3 KIT D816V and HMC1.2 cell
      lines but not on BaF/3 KIT WT cell line. The analysis of bone marrow and
      peripheral blood samples of patients with SM showed KIT surface level increase
      for patients with the KIT D816V mutation but not for patients who had no KIT
      mutation. Interestingly, the extent of KIT level relocalization correlates with
      SM severity, with a higher relocalization for patients with aggressive forms
      compared with indolent forms. CONCLUSIONS: Overall, results of this study
      suggests that treating the peripheral blood sample with dasatinib of a patient
      with SM before analysis by flow cytometry could contribute to narrowing the SM
      diagnosis.

PMID- 23127496
TI  - The dopaminergic stabilizer pridopidine decreases expression of L-DOPA-induced
      locomotor sensitisation in the rat unilateral 6-OHDA model.
AB  - Treatment-limiting motor complications occur in patients with Parkinson's disease
      after chronic levodopa (L-DOPA) treatment, and represent an unmet medical need.
      We examined the motor and neurochemical effects of the dopaminergic stabilizer
      pridopidine (NeuroSearch A/S, Ballerup, Denmark) in the unilateral rodent 6-OHDA
      lesion model, which is often used to evaluate the potential of experimental
      compounds for such dopamine-related motor complications. In total, 72 rats were
      hemi-lesioned and allocated to receive twice-daily injections of either vehicle;
      6.5mg/kg L-DOPA; L-DOPA + 25 MUmol/kg pridopidine; or L-DOPA + 25 MUmol/kg (-)
      OSU6162-a prototype dopaminergic stabilizer used previously in 6-OHDA hemi-lesion
      models. Animals were treated for 7, 14 or 21 days, and locomotor activity and ex
      vivo brain tissue neurochemistry analysed. In agreement with previous studies, L
      DOPA sensitised the motor response, producing significantly more contralateral
      rotations than vehicle (P<0.05). Concomitant administration of pridopidine and L
      DOPA significantly decreased the number of L-DOPA-induced contralateral rotations
      on day 7, 14 and 21 (P<0.05 versus L-DOPA alone), while still allowing a
      beneficial locomotor stimulant effect of L-DOPA. Concomitant pridopidine also
      reduced L-DOPA-induced rotation asymmetry (P<0.05 versus L-DOPA alone) and had no
      adverse effects on distance travelled. Brain neurochemistry was generally
      unaffected in all treatments groups. In conclusion, pridopidine shows potential
      for reducing motor complications of L-DOPA in Parkinson's disease and further
      testing is warranted.

PMID- 23127497
TI  - Anti-inflammatory effect of berkeleyacetal C through the inhibition of
      interleukin-1 receptor-associated kinase-4 activity.
AB  - Berkeleyacetal C (BAC) isolated from Penicillium sp. which had isolated from a
      soil sample collected in Fukushima, inhibited NO production and induction of iNOS
      protein in RAW264.7 cells stimulated by the Toll-like receptor (TLR) 2 ligand,
      peptidoglycan (PGN) or TLR4 ligand, lipopolysaccharide (LPS). The other
      inflammatory mediator production by these stimulators was also suppressed by BAC
      in a concentration-dependent manner. BAC inhibited LPS- or PGN-activated nuclear
      translocation of nuclear factor (NF)-kappaB and MyD88-dependent signaling
      molecules. However, it showed no effect on LPS-induced nuclear translocation of
      interferon regulatory factor (IRF)-3, a MyD88-independent signaling molecule. To
      clarify the mechanistic basis for BAC ability to inhibit translocation of NF
      kappaB and activated MyD88-dependent signaling molecules, we examined interleukin
      1 receptor-associated kinase (IRAK)-4, existing to the most upstream on MyD88
      dependent signaling molecules, in vitro kinase assay. BAC suppressed IRAK-4
      kinase activity in a concentration-dependent manner. These findings suggest that
      BAC inhibits LPS- and PGN- induced NO production and iNOS expression by
      decreasing the level of the translocating of NF-kappaB in nuclear through
      inhibiting the kinase activity of IRAK-4 in inflammatory cells.

PMID- 23127498
TI  - Effect of celecoxib on cyclooxygenase-1-mediated prostacyclin synthesis and
      endothelium-dependent contraction in mouse arteries.
AB  - This study aimed to determine whether a cyclooxygenase-2 (COX-2) inhibitor
      celecoxib influences endothelium-dependent contraction independent of its action
      on COX-2 and, if so, the underlying mechanism(s). Abdominal aortas and/or carotid
      arteries from C57BL/6 mice or those with genetic COX-2 deficiency (COX-2(-/-))
      were isolated for functional and/or biochemical analyses. Result showed that
      following NO synthase inhibition celecoxib not only reduced the contraction
      evoked by acetylcholine in C57BL/6 abdominal aorta, but also that in COX-2 (-/-)
      mice showing a comparable magnitude. Notably, the IC(50) of celecoxib obtained in
      COX-2 (-/-) abdominal aorta was only ~0.364 MUM. Also, celecoxib exhibited a
      similar effect on COX-2 (-/-) carotid arteries. Interestingly, celecoxib was not
      only found to inhibit the production of the prostacyclin (PGI(2)) metabolite 6
      keto-PGF (1alpha) in COX-2 (-/-) aortas, but also caused a reduction in the
      contraction evoked by PGI(2), by the alpha(1)-adrenergic agonist phenylephrine,
      or by 30 mM K(+)-induced depolarization in COX-2 (-/-) and/or C57BL/6 abdominal
      aorta. Moreover, N-[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide (NS398),
      another COX-2 inhibitor, also reduced the contraction evoked by acetylcholine or
      by 30 mM K(+)-induced depolarization in COX-2 (-/-) mice. These results
      demonstrate explicitly that in mouse arteries celecoxib not only inhibits COX-1
      mediated synthesis of PGI(2) and probably some other prostanoids, but also causes
      a reduction in vessel contractility that is independent of either COX-2 or COX-1,
      leading to an inhibition of COX-1-mediated endothelium-dependent contraction with
      an IC(50) value far below that of it considered for COX-1 . Also, our data
      suggest that such effects of celecoxib could be possibly shared by some other COX
      2 inhibitors, such as NS398.

PMID- 23127499
TI  - Down-regulation of 8-oxoguanine DNA glycosylase 1 expression in the airway
      epithelium ameliorates allergic lung inflammation.
AB  - Allergic airway inflammation is characterized by increased expression of pro
      inflammatory mediators, inflammatory cell infiltration, mucus hypersecretion, and
      airway hyperresponsiveness, in parallel with oxidative DNA base and strand
      damage, whose etiological role is not understood. Our goal was to establish the
      role of 8-oxoguanine (8-oxoG), a common oxidatively damaged base, and its repair
      by 8-oxoguanine DNA glycosylase 1 (Ogg1) in allergic airway inflammatory
      processes. Airway inflammation was induced by intranasally administered ragweed
      (Ambrosia artemisiifolia) pollen grain extract (RWPE) in sensitized BALB/c mice.
      We utilized siRNA technology to deplete Ogg1 from airway epithelium; 8-oxoG and
      DNA strand break levels were quantified by Comet assays. Inflammatory cell
      infiltration and epithelial methaplasia were determined histologically, mucus and
      cytokines levels biochemically and enhanced pause was used as the main index of
      airway hyperresponsiveness. Decreased Ogg1 expression and thereby 8-oxoG repair
      in the airway epithelium conveyed a lower inflammatory response after RWPE
      challenge of sensitized mice, as determined by expression of Th2 cytokines,
      eosinophilia, epithelial methaplasia, and airway hyperresponsiveness. In
      contrast, 8-oxoG repair in Ogg1-proficient airway epithelium was coupled to an
      increase in DNA single-strand break (SSB) levels and exacerbation of allergen
      challenge-dependent inflammation. Decreased expression of the Nei-like
      glycosylases Neil1 and Neil2 that preferentially excise ring-opened purines and 5
      hydroxyuracil, respectively, did not alter the above parameters of allergic
      immune responses to RWPE. These results show that DNA SSBs formed during Ogg1
      mediated repair of 8-oxoG augment antigen-driven allergic immune responses. A
      transient modulation of OGG1 expression/activity in airway epithelial cells could
      have clinical benefits.

PMID- 23127500
TI  - Increased monoaminergic neurotransmission improves compliance with physical
      activity recommendations in depressed patients with fatigue.
AB  - Clinical studies have shown that moderately intense physical activity effectively
      treats various types of depression. Beneficial effects have been reported in the
      acute phase of the disease as well as in a long-term perspective. In addition,
      epidemiological studies have shown that inactivity increases the risk of
      depression and that exercise prevents relapse. Depressed patients are often
      prescribed antidepressants, with or without psychotherapy. Some studies have,
      however, suggested that the most frequently used antidepressants, selective
      serotonin reuptake inhibitors (SSRIs), contribute to fatigue, which is a common
      residual symptom associated with depression and the target of the proposed study.
      Profound fatigue may in turn decrease the ability and motivation to perform the
      beneficial physical activity, e.g. via executive dysfunction. Fatigue and
      impaired executive function are commonly linked to disturbed cerebral
      dopaminergic and noradrenergic neurotransmission. This kind of dysfunction is
      hard to overcome, even when the major symptoms of depression are alleviated.
      Interestingly, physical activity has been suggested to improve the dopamine and
      norepinephrine neurotransmission. Furthermore, the favorable effects may be
      reciprocal; improved dopamine and norepinephrine transmission in the brain may
      hypothetically increase the ability and motivation to exercise, since some parts
      of the brain (e.g. the prefrontal cortex, striatum and cerebellum) that control
      movement and initiative receive dopaminergic and noradrenergic projections. Based
      on these findings and assumptions, our hypothesis is that increased dopaminergic
      and noradrenergic neurotransmission, via intake of a dopamine- and norepinephrine
      enhancing agent, improves the compliance with prescribed physical activity in
      patients with depression and residual fatigue. We also believe that the increased
      physical activity can prevent relapse into depression, even after interruption of
      medication. Since increased physical activity also has been shown to improve
      executive cognitive function, we suggest that executive function should be
      examined as a secondary outcome together with other possibly related variables
      such as quality of life, sick leave and BMI.

PMID- 23127501
TI  - Subarachnoid pharmacodialysis for central nervous system disorders.
AB  - We postulate that alternating use of microcontroller-regulated delivery and drain
      pumps connected to one or more sealed subarachnoid fluid exchange ports can
      maintain localized bi-directional molecular fluxes across pia mater covering
      multiple diseased areas of the cerebral cortex or spinal cord. This system
      enables local irrigation with drugs and drainage of endogenous neurotoxic
      molecules normalizing regional neurochemistry and restoring physiological
      function. Viewing the pia mater as an endogenous dialysis membrane, testing this
      hypothesis requires demonstrating: (a) benefits of removing neurotoxic molecules
      from diseased cerebral cortical or spinal areas via subarachnoid dialysis, (b)
      neuropharmacological effects of subarachnoid drug delivery and (c) evaluating
      additive effects of combining the two, as a novel, "pharmacodialysis" procedure.
      Our supporting experimental data show that this procedure can drain
      proinflammatory cytokines from the neocortex to the subarachnoid cerebrospinal
      fluid in rats and can prevent focal seizures in monkeys through subarachnoid
      delivery of muscimol to their neocortex. Subarachnoid pharmacodialysis allows
      effective site-specific treatment and microcontroller-regulated timing responsive
      to the evolving course of a disease and can be performed with bedside systems or
      fully implanted devices. The procedure provides a two-pronged, combined therapy
      for traumatic brain and spinal cord injuries, cortically localized epilepsy,
      stroke and tumors as well as psychiatric disorders such as Alzheimer's disease
      with pathology of the association cortex. Therapeutic subarachnoid
      pharmacodialysis drainage of endogenous molecules from the neocortical
      interstitial space offers unprecedented opportunities to gain new insights into
      the neurochemistry of the human neocortex in real-life conditions over months or
      even years.

PMID- 23127502
TI  - Increasing follicular and stromal cell proliferation in cryopreserved human
      ovarian tissue after long-term precooling prior to freezing: in vitro versus
      chorioallantoic membrane (CAM) xenotransplantation.
AB  - A positive effect on the future development of cells, which have been cooled to
      low suprazero temperatures and then thawed, has been observed before and is not
      new. The aim of this study was to test the effectiveness of postthawing culture
      of human ovarian tissue, which was either frozen just after operative removal or
      cooled after removal to 5 degrees C for 24 h before cryopreservation. Ovarian
      fragments from six patients were divided into small pieces in the form of cortex
      with medulla and randomly divided into the following four groups: Group 1
      consisted of pieces that just after removal had been cultured in vitro for 8 days
      in a big volume of medium with mechanical agitation; Group 2 included pieces
      cooled after operation to 5 degrees C for 24 h and then cultured in vitro for 8
      days; Group 3 was comprised of pieces frozen-thawed just after operation and then
      cultured for 5 days in the chorioallantoic membrane (CAM) culture system; and the
      pieces in Group 4 were cooled after operation to 5 degrees C for 24 h, frozen
      thawed, and then cultured in the CAM system for 5 days. The effectiveness of the
      tissue culture was evaluated by the development of follicles and by the
      intensiveness of proliferation in the tissue (by expression of cytokeratin and Ki
      67). For Groups 1, 2, 3, and 4, the mean densities of follicles per 1 mm(3) was
      12.9, 12.2, 12.4, and 16.1, respectively (p1-2>0.1; p3-4<0.05). For these groups,
      87%, 95%, 71%, and 84% of the preantral follicles were morphologically normal (p1
      2, 3-4<0.05). The immunohistochemical analysis showed increased proliferation
      after cooling of fresh and cryopreserved tissue. Long-term (24 h) cooling of
      ovarian tissue to 5 degrees C before cryopreservation increases the viability of
      the cells in the tissue after thawing. Additionally, the efficacy of the CAM
      system for the culture of thawed human ovarian tissue was demonstrated. 

PMID- 23127503
TI  - Thyroid volume, iodine intake, autoimmune thyroid disorders, inborn factors, and
      endocrine disruptors:  twenty-year studies of multiple effects puzzle in
      Slovakia.
AB  - OBJECTIVE: The aim of this study was to evaluate multiple interrelations between
      several endogenous and exogenous effects and the thyroid volume and function in
      large groups of children, adolescents, and adults with a sufficient whole life
      intake of the iodine. SUBJECTS AND METHODS: The data were obtained either by
      cross sectioned or longitudinal studies in a total of 4998 children and
      adolescents (aged 7 to 17 years) and 2501 adults (1071 males and 1430 females
      aged 20-75 years). Thyroid volume (ThV) was measured by ultrasound, antibodies,
      and hormones by electrochemiluminiscent immunoassay, and endocrine disruptors
      (EDs, polychlorinated biphenyls-PCB, dichlorodiethyl-ichloroethylene-DDE, and
      hexachlorobenzene-HCB) by high resolution gas chromatography/mass spectrometry.
      RESULTS: 1. In large groups of boys and girls of age 7, 10, 13 or 17 years, the
      ThV was significantly higher in the 10th decile than in pooled nine lower
      deciles. Moreover, in 17-year old subjects significantly higher prevalence of
      hypoechogenicity by ultrasound, positive thyroperoxidase antibodies (TPOab), and
      increased thyrotropin (TSH) levels were found in the 10th decile. 2. In a small
      group of children, some individuals revealed consistently higher ThV during the
      whole 7-year follow-up period irrespective of supplementation with iodine. 3. In
      325 sibling pairs of age 10-19 years, born within three years, three groups with
      different ThV/m2 of body surface were distinguished: Group A (183 pairs having
      both ThVs small), Group B (103 pairs having both ThVs large); Group C (33 pairs
      having one ThV small and the other one large). Similar aggregation of ThVs in
      three groups was observed in 13 pairs of discordant twins and 19 sibling triads
      in which all the siblings were born within four years. 4. In 42 concordant twins,
      several pairs had ThV nearly twice as high (in terms of both plain ThV or ThV/m2
      of the body surface) as several other pairs of the same age which is assumed to
      be a result of a genetic background. 5. In large cohorts of males and females, a
      highly significant positive correlation was found between the ThV and high level
      of TPOab on one side and EDs on the other side. However, in nearly the same
      numbers of subjects with low TPOab, negative correlation was seen between ThV and
      disruptors. These observations may apparently support the synergic effect of the
      autoimmunity and EDs on the thyroid function. CONCLUSIONS: Several cases of an
      excessive thyroid growth in the iodine replenished children, adolescents, and
      adults may apparently result from the autoimmune thyroiditis, probably induced by
      immunogenic action of iodine in presumably disposed individuals. However, in some
      cases even simultaneous participation of EDs can not be excluded. Some
      observations have also suggested that excessive thyroid growth in the iodine
      replenished adolescent and adult population which was equally exposed to
      disruptors may also result from other reasons as the unfavorable hereditary
      background.

PMID- 23127504
TI  - Modified endogenous carbon monoxide production through modulation of heme
      oxygenase activity alters some aspects of the cold restraint stress response in
      male albino rats.
AB  - OBJECTIVE: Multiple stimulatory and inhibitory inputs regulate the hypothalamic
      pituitary-adrenal axis (HPA). Although the results of the previous studies are
      contradictory, it has been indicated that the carbon monoxide (CO) may play a
      role in the HPA regulation. The aim of the present study was to investigate the
      effect of modified endogenous CO production on some aspects of the cold restraint
      stress (CRS) response in adult male albino rats. METHODS: Modification of the
      endogenous CO was performed by altering the heme oxygenase (HO) activity; its
      induction was achieved by administration of the hemin (HEM) and inhibition by
      administration of the zinc mesoporphyrin (ZM). RESULTS: We found that in both the
      non-stressed and stressed groups the HEM significantly decreased the plasma
      levels of epinephrine (EPI), adrenocorticotropic hormone (ACTH), corticosterone
      (B), cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C),
      and low-density lipoprotein cholesterol (LDL-C). On the other hand, ZM
      significantly increased the adrenal EPI, norepinephrine (NE), dopamine (DA), and
      the plasma levels of EPI, NE, DA, ACTH, B, cholesterol, triglycerides, HDL-C, and
      LDL-C, as compared with control and stressed rats. CONCLUSION: The role of CO
      reaction to the CRS response could be clarified as an anti-stress effect. This is
      evidenced by the inhibitory effect of HO inducer, HEM, on the HPA axis and a
      consequent less hazardous metabolic profile which it produced. KEYWORDS: carbon
      monoxide, hemin, heme oxygenase, stress.

PMID- 23127505
TI  - A new approach of light microscopic immunohistochemical  triple-staining:
      combination of Fos labeling with diaminobenzidine-nickel and neuropeptides
      labeled with Alexa488 and Alexa555 fluorescent dyes.
AB  - OBJECTIVE: The aim of the present study was to introduce a new approach of the
      light microscopic immunohistochemical triple-staining enabling to study the
      differences in the activity of at least two different phenotypes of neurons on
      the same histological section. For this purpose combination of Fos (a product of
      the immediate early gene) labeling with nickel intensified diaminobenzidine (DAB
      Ni) and two neuropeptides labeled with Alexa488 and Alexa555 fluorescent dyes on
      cryo-processed 35-40 um thick free-floating brain sections was selected. METHODS:
      The parallel occurrence of three antibodies studied, i.e. Fos, hypocretin (HCRT),
      and melanin-concentrating hormone (MCH), was studied by a new methodic approach
      utilizing combination of Fos immunolabeled with DAB-Ni and HCRT and MCH labeled
      with Alexa488 and Alexa555 fluorescent dyes, respectively. Fos stimulation was
      induced by a single immobilization (IM0) for 120 min. Then, the rats were
      sacrificed, the brains removed, soaked with 30% sucrose in 0.1 M phosphate buffer
      (PB), cryo-sectioned throughout the hypothalamus into 35-40 MUm thick coronal
      sections, collected, and washed in the same buffer for 10-15 min. Fos was
      revealed by avidin-biotin-peroxidase (ABC) complex and visualized by
      diaminobenzidine chromogen containing nickel chloride salt. HCRT and MCH neurons
      were visualized by the above mentioned fluorescent dyes. Evaluation of the Fos
      and fluorescent staining was performed in the computerized Axo Imager Carl Zeiss
      microscope using light and fluorescent illuminations. RESULTS: All the antibodies
      used showed clear immunoreactive staining. Fos staining occurred in the form of
      black color located in the cell nuclei. HCRH and MCH neuropeptides showed clear
      green and red fluorescence in the cell perikarya, respectively. The final merged
      picture showed Fos protein in the activated green HCRT or red MCH neurons in the
      form of white nuclei. CONCLUSIONS: The present study clearly demonstrate that the
      combination of Fos labeling with DAB-Ni and neuropeptides labeled with Alexa488
      and Alexa555 on cryo-processed 35-40 um thick free-floating brain sections is an
      excellent approach providing further advantages for quick and reproducible triple
      immuno-staining enabling to compare the activity of at least two phenotypes of
      neurons on the same section. KEYWORDS: Alexa488 and Alexa555 fluorescent dyes,
      Fos, hypocretin, melanin-concentrating hormone, cryostat sections, triple
      labeling immunohistochemistry, rat.

PMID- 23127506
TI  - Regulation of cumulus expansion and hyaluronan synthesis in porcine oocyte
      cumulus complexes during in vitro maturation.
AB  - This review deals with molecular mechanisms controlling three important ovarian
      follicular processes: 1) expansion of the cumulus, 2) synthesis of the hyaluronan
      (HA), and 3) production of the progesterone in oocyte cumulus complexes (OCCs).
      The expansion of the mice cumuli induced by FSH or 8-bromo cAMP is dependent upon
      a specific factor(s) secreted by the oocyte (called "cumulus expansion enabling
      factor", CEEF). The porcine oocytes produce at least two factors that have
      influence on the formation and stability of the preovulatory extracellular
      cumulus matrix (ECM), although oocytectomy does not alter the ability of the
      cumulus cells to respond to FSH and forskolin by increased cAMP content, HA
      synthesis, and subsequent cumulus expansion, The net synthesis of HA, during the
      FSH-stimulated expansion of the OCCs in the presence of serum, correlates
      directly with accumulation of glycosaminoglycans in the ECM. In pig, insulin
      growth factor 1 (IGF1) is a component of the serum that promotes the FSH
      stimulated synthesis and retention of HA within the expanded ECM by
      phosphatidylinositol 3-kinase (PI3K)/v-akt murine thymoma viral oncogene homolog
      (AKT)- and mitogen-activated kinase 3 and 1 (MAPK3/1)-dependent mechanisms.
      Mouse, porcine, bovine, and rat oocytes produce CEEF(s). Possible candidate for
      the CEEF in the mouse is growth differentiation factor 9 (GDF9) secreted by
      oocytes. In pig, GDF9 mRNA is expressed not only in the oocytes but also in the
      cumulus and mural granulosa cells of the growing and preovulatory follicles,
      although the relative abundance of the GDF9 in the somatic cells is approximately
      4 times lower than in the oocytes. Cross talk between FSH/ epidermal growth
      factor receptor (EGFR) and transforming growth factor beta (TGFbeta)/GDF9
      signaling pathways is essential for functional activities of the porcine OCCs,
      since FSH enhances EGF-induced tyrosine phosphorylation of EGFR, indicating that
      FSH signaling pathway may stimulate specific EGFR-regulating proteins. Also, FSH
      induced synthesis of both HA and progesterone is reduced but not abolished by
      AG1478 (EGFR tyrosine kinase inhibitor), indicating that other signaling pathways
      elicited by FSH are operating in parallel. Furthermore, SMAD2/3 signaling pathway
      is involved in the control of both cumulus expansion and steroidogenesis in
      porcine OCCs, since SMAD2/3 activation by GDF9/ TGFbeta produced by oocyte and/or
      cumulus cells, significantly affects gonadotropin-induced HA and progesterone
      synthesis by porcine cumulus cells. KEYWORDS: oocyte-cumulus complex, hyaluronan,
      progesterone, cumulus expansion.

PMID- 23127507
TI  - Role of interleukins in the regulation of ovarian functions.
AB  - Reproduction is a result of coordinated signaling network between gonads and
      pituitary/hypothalamus. Ovarian functions, such as follicular development,
      ovulation, luteinisation, luteolysis, and remodeling of the endometrium, are
      controlled by endocrine, paracrine and autocrine factors. Ovulation is a unique
      biological process by which the complex of a mature oocyte and surrounding
      somatic cumulus cells (CCs), named oocyte-cumulus complex (OCC), is released from
      the follicle into the oviduct for transport and fertilization. Recently, evidence
      has been accumulated that the immune system might represent an additional local
      regulator of the ovarian functions that are essentially modulated by
      gonadotropins. Moreover, the ovulation is similar to an inflammatory response:
      follicles become hyperemic, produce prostaglandins (PGs), and synthesize a
      hyaluronan-rich extracellular matrix. Cytokines are originally referred as
      numerous signaling substances secreted by certain cells of the immune system
      which influence the activity of other cells. A number of studies have shown that
      cytokines may modulate ovarian functions and play an important role in the
      ovulation. The most known cytokines related to the reproduction are interleukins
      (ILs). These molecules have been localized in the reproduction-related body
      fluids and various ovarian cell types, such as the oocytes, granulosa (GCs) and
      theca cells (TCs) in several mammalian species. Moreover, macrophages in the
      ovary have been shown to secrete cytokines, including ILs. The present review
      summarizes the current knowledge on ILs in regard of their role in the regulation
      of selected ovarian functions. KEYWORDS: cytokines, interleukins, ovary,
      steroidogenesis, ovulation, corpus luteum.

PMID- 23127508
TI  - Nano- and microscaled particles for drug targeting to inflamed intestinal mucosa:
      a first in vivo study in human patients.
AB  - Most of the drugs used in the treatment of inflammatory bowel disease (IBD)
      become systemically bioavailable and potentially bear strong adverse effects.
      Targeting the inflamed areas of the intestine and keeping the drug localised at
      its site of action can reduce adverse effects. In animal studies, luminal uptake
      into inflamed mucosal areas has been shown to be size dependent. We investigated
      the potential of nano- and microparticle uptake into the rectal mucosa of human
      IBD patients. Fluorescently labelled placebo nanoparticles (NP) 250nm in size and
      microparticles (MP) 3.0MUm in size were prepared. 2h after rectal application to
      patients with Crohn's disease (CD) or ulcerative colitis (UC), confocal laser
      endomicroscopy was performed to visualise the particles in inflamed mucosal
      areas. In biopsies, ex vivo mucosal transport processes were investigated in
      miniaturised Ussing chambers. We examined 33 patients with IBD (19 patients with
      CD, 14 patients with UC) and 6 healthy controls. A significantly enhanced
      accumulation of MP in ulcerous lesions was observed (covered area=1.28% (range
      0.83%-3.45%) vs. 0% in controls; p=0.011), while NP were visible only in traces
      on mucosal surfaces of all patients. The Ussing chamber experiments suggest
      persorption of particles through cellular voids; statistical significance was
      only reached for NP. Drug-containing particles may have great potential to more
      specifically target intestinal lesions to maximise therapeutic efficacy and
      minimise potential side effects. Nanoparticles may not be required for local drug
      delivery to intestinal lesions in humans, thereby minimising the risk of
      unintended translocation into the blood system.

PMID- 23127509
TI  - Dementia skills and competencies for primary care liaison: a model for improving
      identification and timely diagnosis.
AB  - OBJECTIVES: The need to improve the response of primary care in terms of
      identification of people with undiagnosed dementia has long been recognised. The
      role of Primary Care Liaison was identified as a possible solution. An in-depth
      consultation was undertaken to identify professional competencies required in
      executing such a role. METHODS: Comprehensive literature and policy reviews were
      conducted to establish draft competencies or different options/combinations of
      competencies and competency levels. Consultations with a wide range of
      professional stakeholders (n = 23) and over 70 users and carers were conducted
      through focus groups, electronic document circulation and telephone interviews.
      An Equality Impact Assessment was conducted concurrent to the consultation.
      RESULTS: The literature demonstrated a clear need both to improve the rate of
      diagnosis for people with dementia and to improve the way in which the diagnosis
      is made. The stakeholder consultation repeatedly affirmed that without a
      diagnosis the person with dementia and their caregivers did not get access to the
      appropriate services, and validated the need for a role that would be able to
      improve a system that would deliver an early and 'timely' diagnosis.
      Competencies, based on the literature and policy documents, were developed and
      debated through the consultation processes. CONCLUSIONS: Three main areas of
      competency were identified: counselling; screening; and health education and
      promotion. The competencies identified require a skilled experienced professional
      approach. A useful team model would be that the role is placed within a 'GP
      cluster' as accessibility to GP records and collaborative working with GPs is
      essential within the role. Personal continuing professional development has a
      high profile in maintaining these competencies.

PMID- 23127510
TI  - Atomic force microscopy characterization of collagen 'nanostraws' in human costal
      cartilage.
AB  - Costal cartilage, a type of hyaline cartilage that bridges the bony ribs and
      sternum, is relatively understudied compared to the load bearing cartilages.
      Deformities of costal cartilage can result in deformation of the chest wall,
      where the sternum is largely pushed toward or away from the spine, pectus
      excavatum and pectus carinatum, respectively, with each condition having
      significant clinical impact. In the absence of extensive literature describing
      morphological features of costal cartilage, we characterized a sample from the
      costal margin immunohistologically and through atomic force microscopy. We had
      previously observed the presence of collagen 'nanostraws' running the length of
      costal cartilage. Hypothesizing that these structures may be responsible for
      fluid flow within this thick, avascular tissue, and prior to microfluidic
      analysis, we estimated the diameters and measured Young's modulus of elasticity
      of the collagen nanostraws. We found significant differences in results between
      treatment type and fixation. Significant differences in nanostraw elasticity and
      diameter obviously affect nano-fluidic transport calculations, and therefore, we
      consider these results of importance to the scientific community relying upon
      measurements in the nanoscale.

PMID- 23127511
TI  - Metabolism and breast cancer risk: frontiers in research and practice.
AB  - Fifty years ago the causes of cancer were largely unknown. Since then, it has
      become clear that a strong relationship exists between obesity and many cancers,
      particularly postmenopausal breast cancer. A major challenge in understanding the
      link between obesity and cancer risk has been elucidating the biological basis
      underlying the association. Although this remains unresolved, the main candidate
      systems linking adiposity and cancer risk are insulin and the insulin-like growth
      factor-1 axis, endogenous reproductive hormones, and chronic inflammation. Our
      purpose is to provide a mechanistic overview of the hypothesized relationship
      between diet, physical activity, and obesity with breast cancer risk and
      progression. In addition, we will provide examples of recently funded randomized
      clinical trials examining metabolic risk factors in relation to breast cancer
      risk and survival. Additional research is warranted to validate the strength and
      consistency of the relationships among diet, these biomarkers, and breast cancer
      risk. As these relationships become clearer, future studies will be needed to
      develop effective intervention programs to prevent breast cancer and improve
      cancer prognosis by promoting a healthy lifestyle.

PMID- 23127512
TI  - Mitigation of radiation injury by selective stimulation of the LPA(2) receptor.
AB  - Due to its antiapoptotic action, derivatives of the lipid mediator
      lysophosphatidic acid (LPA) provide potential therapeutic utility in diseases
      associated with programmed cell death. Apoptosis is one of the major
      pathophysiological processes elicited by radiation injury to the organism.
      Consequently, therapeutic explorations applying compounds that mimic the
      antiapoptotic action of LPA have begun. Here we present a brief account of our
      decade-long drug discovery effort aimed at developing LPA mimics with a special
      focus on specific agonists of the LPA(2) receptor subtype, which was found to be
      highly effective in protecting cells from apoptosis. We describe new evidence
      that 2-((3-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)propyl)thio)benzoic acid
      (GRI977143), a prototypic nonlipid agonist specific to the LPA(2) receptor
      subtype, rescues apoptotically condemned cells in vitro and in vivo from injury
      caused by high-dose gamma-irradiation. GRI977143 shows the features of a
      radiomitigator because it is effective in rescuing the lives of mice from deadly
      levels of radiation when administered 24h after radiation exposure. Our findings
      suggest that by specifically activating LPA(2) receptors GRI977143 activates the
      ERK1/2 prosurvival pathway, effectively reduces Bax translocation to the
      mitochondrion, attenuates the activation of initiator and effector caspases,
      reduces DNA fragmentation, and inhibits PARP-1 cleavage associated with gamma
      irradiation-induced apoptosis. GRI977143 also inhibits bystander apoptosis
      elicited by soluble proapoptotic mediators produced by irradiated cells. Thus,
      GRI977143 can serve as a prototype scaffold for lead optimization paving the way
      to more potent analogs amenable for therapeutic exploration. This article is part
      of a Special Issue entitled Advances in Lysophospholipid Research.

PMID- 23127513
TI  - Preubiquitinated chimeric ErbB2 is constitutively endocytosed and subsequently
      degraded in lysosomes.
AB  - The oncoprotein ErbB2 is endocytosis-deficient, probably due to its interaction
      with Heat shock protein 90. We previously demonstrated that clathrin-dependent
      endocytosis of ErbB2 is induced upon incubation of cells with Ansamycin
      derivatives, such as geldanamycin and its derivative 17-AAG. Furthermore, we have
      previously demonstrated that a preubiquitinated chimeric EGFR (EGFR-Ub(4)) is
      constitutively endocytosed in a clathrin-dependent manner. We now demonstrate
      that also an ErbB2-Ub(4) chimera is endocytosed constitutively and clathrin
      dependently. Upon expression, the ErbB2-Ub(4) was further ubiquitinated, and by
      Western blotting, we demonstrated the formation of both Lys48-linked and Lys63
      linked polyubiquitin chains. ErbB2-Ub(4) was constitutively internalized and
      eventually sorted to late endosomes and lysosomes where the fusion protein was
      degraded. ErbB2-Ub(4) was not cleaved prior to internalization. Interestingly,
      over-expression of Ubiquitin Interaction Motif-containing dominant negative
      fragments of the clathrin adaptor proteins epsin1 and Eps15 negatively affected
      endocytosis of ErbB2. Altogether, this argues that ubiquitination is sufficient
      to induce clathrin-mediated endocytosis and lysosomal degradation of the
      otherwise plasma membrane localized ErbB2. Also, it appears that C-terminal
      cleavage is not required for endocytosis.

PMID- 23127514
TI  - Leucine-rich repeat-containing G protein-coupled receptor 5 regulates epithelial
      cell phenotype and survival of hepatocellular carcinoma cells.
AB  - The leucine-rich repeat containing G protein-coupled receptor 5 (LGR5), also
      known as GPR49, is a seven-transmembrane receptor that is expressed in stem cells
      of the intestinal crypts and hair follicles of mice. LGR5 is overexpressed in
      some types of human cancer, and is one of the target genes of the Wnt signaling
      pathway. To explore the function of LGR5 in cancer cells, stable hepatocellular
      carcinoma (HCC) cell lines expressing FLAG-tagged LGR5 were established.
      Overexpression of LGR5 resulted in changes in cell shape from an extended flat
      (mesenchymal) phenotype to a round aggregated (stem cell-like) phenotype. Cells
      transfected with LGR5 showed higher colony forming activity, and were more
      resistant to a cytotoxic drug than cells transfected with empty vector.
      Overexpression of LGR5 inhibited cell motility. LGR5-transfected cells formed
      nodule type tumors in the livers of immunodeficient mice, whereas empty vector
      transfected cells formed more invasive tumors. Down-regulation of LGR5 changed
      the morphology of HCC cells from the aggregated phenotype to an extended spindle
      phenotype, and cell motility was increased. This is the first study reporting the
      functional role of LGR5 in the biology of HCC cells, and the results suggest that
      aberrant expression of LGR5 regulates epithelial cell phenotype and survival.

PMID- 23127515
TI  - Using data to guide policy: next steps for preventing perinatal hepatitis B virus
      transmission in Cambodia.
AB  - BACKGROUND: Cambodia is highly endemic for hepatitis B virus (HBV) infection.
      Preventing perinatal HBV transmission should be prioritized in health facilities
      by providing hepatitis B vaccination to all infants within 24 h of birth (timely
      birth dose coverage). METHODS: Teams assessed birth dose policy, practices and
      coverage in hospitals and health facilities in 10 provinces in Cambodia. RESULTS:
      Fifty-one sites were assessed. Median (interquartile range) timely birth dose
      coverage was 66% (48-92%); coverage was 88% (range=60-96%) in facilities
      vaccinating on-site and 48% (range=20-52%) in those referring off-site
      (p<0.0001). Overall, 5 (29%) of 16 hospitals that referred vaccination off-site
      did not tell mothers vaccination should take place within 24 h of birth, and 6
      (35%) discharged mothers when no vaccination services were available for infants
      to receive the birth dose. CONCLUSIONS: Newborns can miss a time-sensitive
      opportunity to be protected against perinatal HBV infection when they are
      referred for vaccination off-site rather than being vaccinated in the delivery
      facility. These data support the case to strengthen policies and practices to
      provide hepatitis B birth dose vaccination in the delivery facility.

PMID- 23127516
TI  - Effectiveness of the Lanzhou lamb rotavirus vaccine against gastroenteritis among
      children.
AB  - The Lanzhou lamb rotavirus (LLR) vaccine has been in use in China since 2000.
      This study evaluated this vaccine's effectiveness using a case-control design in
      Guangzhou. In the study area, there were 3130 laboratory-confirmed rotavirus
      gastroenteritis cases in children between 2 and 35 months old from 2009 to 2011.
      A total of 3607 controls were also enrolled in this study. Of the subjects, 970
      (14.4%) had received 1 dose of the LLR vaccine. Because of the low vaccination
      rate, we only obtained an effectiveness of 44.3% (95% CI, 28.4-56.7%) for
      children 9-11 months old, 52.8% (40.8-62.3%) for children 12-17 months old, and
      51.8% (11.6-73.8%) for children 18-35 months old for one dose. This post
      marketing study found that one dose of the LLR vaccine confers partial protection
      when given to children between 9 and 35 months old. Therefore, earlier
      immunization and the administration of the full immunization regimen should be
      encouraged.

PMID- 23127517
TI  - [Invasive fungal infection in solid organ transplant].
AB  - Invasive fungal infections (IFI) represent a serious threat for patients
      undergoing solid organ transplantation (SOT). IFI in SOT has a significant
      incidence and mortality not due to negligence. The management of IFI in SOT
      involves specific recommendations and has been individualized to the type of
      transplant and patient. The current review presents an overview of epidemiology,
      diagnosis, treatment and prevention of IFI in TOS. Depending on risk factors for
      different IFIs and transplant type, this paper includes the main recommendations
      based on previous publications and on the opinion of the authors on the
      prophylaxis and treatment of these patients. These recommendations highlight
      epidemiology changes and the emergence of new antifungals. The current document
      has focused mainly on Candidaspp. and Aspergillusspp., with a special mention to
      the rest of yeasts and moulds that are common in SOT.

PMID- 23127518
TI  - A new family of cystine knot peptides from the seeds of Momordica
      cochinchinensis.
AB  - Momordica cochinchinensis, a Cucurbitaceae plant commonly found in Southeast
      Asia, has the unusual property of containing both acyclic and backbone-cyclized
      trypsin inhibitors with inhibitor cystine knot (ICK) motifs. In the current study
      we have shown that M. cochinchinensis also contains another family of acyclic ICK
      peptides. We recently reported two novel peptides from M. cochinchinensis but
      have now discovered four additional peptides (MCo-3-MCo-6) with related
      sequences. Together these peptides form a novel family of M. cochinchinensis ICK
      peptides (MCo-ICK) that do not have sequence homology with other known peptides
      and are not potent trypsin inhibitors. Otherwise these new peptides MCo-3 to MCo
      6 were evaluated for antimalarial activity against Plasmodium falciparum, and
      cytotoxic activity against the cancer cell line MDA-MB-231. But these peptides
      were not active.

PMID- 23127519
TI  - School-based sex education is associated with reduced risky sexual behaviour and
      sexually transmitted infections in young adults.
AB  - OBJECTIVE: To quantify the effectiveness of school-based sexual education on
      risky sexual behaviour and sexually transmitted infection (STI) acquisition in
      adulthood. STUDY DESIGN: Online survey of sexual attitudes and behaviours.
      METHODS: Students at a British university were surveyed regarding where they
      learnt most about sex at 14 years of age, how easy they found talking about
      sexual issues with their parents and age at first intercourse. The effects of
      these factors were modelled on risk of recent unprotected intercourse and self
      reported STIs in adulthood. RESULTS: Seventy-eight of 711 (11%) students reported
      unprotected intercourse in the 4 weeks before the survey, and 44 (6.2%) students
      had ever been diagnosed with an STI. Both age at first intercourse (risk reduced
      by 11% per year of delayed intercourse, 95% confidence interval (CI) 3-19%) and
      learning about sex from lessons at school (66% reduction in risk compared with
      learning from one's mother, 95% CI 5-88%) were associated with reductions in risk
      of unprotected intercourse. Factors associated with fewer STIs were age at first
      intercourse (17% reduction per year of delayed intercourse, 95% CI 5-28%); and
      learning about sex from lessons at school (85% reduction, 95% CI 32-97%), from
      friends of the same age (54% reduction, CI 7-77%) and from first boy/girlfriend
      (85% reduction, 95% CI 35-97%) compared with learning from one's mother.
      CONCLUSION: School-based sexual education is effective at reducing the risk of
      unprotected intercourse and STIs in early adulthood. Influence from friends in
      adolescence may also have a positive effect on the risk of STIs in later life.

PMID- 23127520
TI  - 'It's a regional thing': financial impact of renal transplantation on live
      donors.
AB  - INTRODUCTION: There has been no research exploring the financial impact on the
      live renal donor in terms of testing, hospitalisation and surgery for kidney
      removal (known as nephrectomy). The only mention of financial issues in relation
      to live renal transplantation is the recipients' concerns in relation to monetary
      payment for the gift of a kidney and the recipients' desire to pay for the costs
      associated with the nephrectomy. The discussion in this article posits a new
      direction in live renal donor research; that of understanding the financial
      impact of live renal donation on the donor to inform health policy and supportive
      care service delivery. The findings have specific relevance for live renal donors
      living in rural and remote locations of Australia. METHODS: The findings are
      presented from the first interview (time 1: T1) of a set of four times (time 1 to
      time 4: T1-T4) from a longitudinal study that explored the experience of live
      renal donors who were undergoing kidney removal (nephrectomy) at the Renal
      Transplantation Unit at the Princess Alexandra Hospital, Brisbane, Australia. A
      qualitative methodological approach was used that involved semi-structured
      interviews with prospective living kidney donors (n=20). The resulting data were
      analysed using the qualitative research methods of coding and thematic analysis.
      RESULTS: The findings indicate that live renal donors in non-metropolitan areas
      report significant financial concerns in relation to testing, hospitalisation and
      surgery for nephrectomy. These include the fact that bulk billing (no cost to the
      patient for practitioner's service) is not always available, that individuals
      have to pay up-front and that free testing at local public hospitals is not
      available in some areas. In addition, non-metropolitan donors have to fund the
      extra cost of travel and accommodation when relocating for the nephrectomy to the
      specialist metropolitan hospital. CONCLUSION: Live renal transplantation is an
      important new direction in medical care that has excellent long-term results for
      individuals diagnosed with end-stage renal disease. An essential element of the
      transplantation procedure is the voluntary donation of a healthy kidney by the
      live renal donor. Such an altruistic gift, which has no personal health benefit
      for the donor, is to be applauded and supported. The present research
      demonstrates that for some donors, particularly those living outside the
      metropolitan area, the gift may also include a range of financial costs to the
      donor. There is no prior research available on the financial impact of live renal
      donation for individuals living in non-metropolitan areas. Thus, this article is
      a seminal work in the area. The findings affirm 'rural disadvantage' by
      demonstrating that it is the live renal donors in non-metropolitan areas who are
      reporting financial concerns in relation to testing, hospitalisation and surgery
      for nephrectomy. It is the hope and expectation that the reporting on these costs
      will encourage further work in this area and the findings will be used for health
      policy and service delivery considerations.

PMID- 23127521
TI  - Effect of water withdrawal on formation of free radical, proline accumulation and
      activities of antioxidant enzymes in ZAT12-transformed transgenic tomato plants.
AB  - Water stress often leads to the accumulation of reactive oxygen species (ROS) and
      their excessive production alters the activities of enzymes involved in their
      removal. ZAT12 is a member of stress-responsive C(2)H(2) type Zinc Finger Protein
      (ZFP) reported to control the expression of several stress-activated genes in
      plants through ROS signaling. The ZAT12-transformed tomato lines (cv. H-86
      variety Kashi Vishesh) when subjected to water withdrawal for 7, 14 and 21 days
      revealed significant and consistent changes in activities of enzymes SOD, CAT,
      APX, GR and POD paralleled with an increased proline levels. Unlike that in wild
      type tomato, the leaf superoxide anion and hydrogen peroxide concentrations in
      the transformed tomato plants did not alter much, suggesting a well regulated
      formation of free radicals suppressing oxidative stress in the latter. Results
      suggest BcZAT12-transformed tomato lines ZT1, ZT2 and ZT6 to be better adapted to
      drought stress tolerance by accumulation of osmolyte proline and increased
      antioxidant response triggered by the ZAT12 gene. Therefore, the ZAT12
      transformed tomato cv. H-86 lines will prove useful for higher yield of tomato
      crop in regions affected with severe drought stress.

PMID- 23127522
TI  - Melatonin enhances root regeneration, photosynthetic pigments, biomass, total
      carbohydrates and proline content in the cherry rootstock PHL-C (Prunus avium *
      Prunus cerasus).
AB  - The present study, investigates the effects of melatonin (0, 0.05, 0.1, 0.5, 1, 5
      and 10 MUM) on the morphogenic and biochemical responses in the cherry rootstock
      PHL-C (Prunus avium L. * Prunus cerasus L.), from shoot tip explants. The
      incorporation of melatonin (0-10 MUM) in the Murashige and Skoog (MS) medium,
      greatly influenced rooting either positively or negatively. Melatonin,
      irrespective of its concentration, had a negative effect concerning the number of
      roots. However, application of 0.5 MUM melatonin significantly increased the root
      length; while 1 MUM melatonin increased the root length by 2.5 times, and the
      fresh weight of the roots by 4 times, in comparison to the control. Although 0.05
      MUM melatonin increased rooting by 11.11%, 5 MUM melatonin had a significant
      reduction on the number, the fresh weight of roots, and the rooting percentage.
      Melatonin concentration of 0.1 MUM resulted in the greatest chlorophyll (a + b)
      content, and 5-10 MUM reduced the chlorophyll concentration by 2 times, compared
      to the control. The high melatonin concentrations (5 and 10 MUM), increased the
      levels of proline and carbohydrates in leaves by 3-4 times. In the roots, 0.5 MUM
      of melatonin concentration increased the carbohydrate levels by 1.5 times, while
      0.05, 0.1 and 1 MUM melatonin concentration significantly reduced the proline
      content.

PMID- 23127523
TI  - DEVDase activity is induced in potato leaves during Phytophthora infestans
      infection.
AB  - Programmed cell death (PCD) occurs in plants, animals and several branches of
      unicellular eukaryotes as a part of developmental and/or defense processes.
      Caspase proteases are universal mediators of animal apoptosis, a type of PCD. In
      plants, there are not animal caspase homologs; therefore, the characterization of
      caspase-like activities is of considerable importance to our understanding of PCD
      in plants. Here we report for the first time the involvement of caspase-3-like
      activity in the resistance mechanism of potato to Phytophthora infestans
      infection. We showed that disease development in infected potato leaves is
      dependent of caspase-3-like activity. Unlike plant DEVDases previously reported,
      this DEVDase activity was sensitive to the serine protease inhibitor PMSF. As
      reported for other subtilisin- like proteases with caspase activity, potato
      DEVDase activity was mainly localized in the apoplast. We demonstrated that in
      total protein extract DEVDase activity accounts for a 60% of serine proteases;
      however, this percentage increases to 100% in the apoplast. Additionally, this
      caspase-3-like activity is constitutively expressed in the apoplast of potato
      leaves. Total DEVDase activity is induced only in potato cultivars with high
      field resistance to P. infestans. These results show that potato caspase-3-like
      protease could constitute a tool in the potato defense mechanisms resulting in
      partial resistance, although further assays would be necessary in order to
      elucidate its role.

PMID- 23127524
TI  - Nutritional and host effects on methanogenesis in the grazing ruminant.
AB  - Concentrations of methane (CH(4)) in the atmosphere have almost doubled since the
      mid 1700s, and it is estimated that ~30% of the global warming experienced by the
      planet in the last century and a half can be attributed to CH(4). Between 25% and
      40% of anthropogenic CH(4), emissions are estimated to arise from livestock
      farming. Mitigating absolute emissions from livestock is extremely challenging
      technically and is made more difficult because of the need to increase food
      production to meet the demands of a burgeoning world population. Opportunities
      for manipulating the diet of intensively managed ruminant to reduce absolute
      CH(4) exist, but in grazing livestock the opportunities are constrained
      practically and economically. Mitigating emissions per unit of product is more
      tractable, especially in the short term. Although the formation of CH(4) is an
      anaerobic microbiological process, the host animal does seem to exert an
      influence, as animals differ in the quantity of CH(4) they emit when fed the same
      diet. The reasons for this are not yet clear, but evidence is accumulating that
      these differences are consistent and have a genetic basis. Exploiting these
      between animal differences by animal breeding is an attractive mitigation option
      as it is potentially applicable to all animals and is open to continuous
      improvement. However, identifying the desired phenotype poses severe practical
      constraints. Vaccinating the host animal to produce antibodies that can modulate
      the activities of the organisms responsible for CH(4) formation also presents a
      novel mitigation option.

PMID- 23127525
TI  - Effects of exercise interventions in graft-versus-host disease models.
AB  - Graft-versus-host-disease (GVHD) is a major complication of allogeneic
      hematopoietic stem cell transplantation (allo-HSCT), which is associated with
      high morbimortality and decreased patients' physical capacity. We evaluated the
      effects of an 11-week moderate-intensity exercise (treadmill) training program
      performed after allo-HSCT in a murine acute (aGVHD) and chronic GVHD model
      (cGVHD). Female mice (aged 8-12 weeks) were randomly assigned to the exercise or
      the control group. They completed a maximal treadmill test before allo-HSCT (with
      donor bone marrow cells and splenocytes) and after the 11-week period, during
      which we evaluated clinical severity scores and survival (Kaplan-Meier method).
      Before allo-HSCT and at days +21, +52 and +83 (upon sacrifice), we collected
      blood samples for immune cell reconstitution and cytokine analysis. The main
      results were that (i) in aGVHD, exercise improved maximal physical capacity over
      the 11-week period compared with pre-allo-HSCT conditions (p < 0.001 for the
      between-group comparison) and benefited total clinical score evolution (p = 0.05
      for the group * time interaction effect), without altering immune reconstitution;
      (ii) in cGVHD, exercise training resulted in a lesser deterioration of physical
      capacity after 11 weeks (p = 0.023). Our results highlight the potential
      beneficial effects of exercise as coadjuvant intervention against GVHD,
      especially in the acute form of the disease. 

PMID- 23127526
TI  - Cathepsins and pancreatic cancer: the 2012 update.
AB  - Pancreatic cancer is the result of distinctive genetic and epigenetic
      disturbances. This multistep process is in part well-defined and includes
      alterations in oncogenes and suppressor genes that control proliferation,
      apoptosis, angiogenesis, invasion and cell migration. Cathepsins are proteolytic
      enzymes and represent potential therapeutic targets in human tumors. Cathepsins
      predominantly function as endopeptidases within endolysosomal vesicles of normal
      cells and they are involved in physiological processes such as protein turnover,
      differentiation and apoptosis. In various types of malignancies, cathepsins have
      been associated with tumor progression and metastasis. Growing evidence and
      direct proofs suggest that cathepsins are highly up-regulated in pancreatic
      cancer and contribute to the development and progression of the cancer phenotype.
      In this review, the role of cathepsins in pancreatic cancer tumorigenesis is
      reported and discussed. Some critical aspects will be underlined such as
      specificity of cathepsin activity in pancreatic cancer and in its precursor
      lesions; the genetic perturbation and the intracellular signaling pathway
      activated by cathepsins as reported in preclinical models and in human tissues;
      the preliminary results and the oncological effects of cathepsin inhibitors
      currently tested on pancreatic cancer cells; the role of combined therapy based
      on chemotherapeutic agents and cathepsin inhibition. Although mounting evidences
      indicate that cysteine cathepsins are potential therapeutic targets in pancreatic
      cancer, as suggested by their functional role in controlling invasiveness and
      metastasis, it remains to be seen whether the promising benefits of
      pharmacological inhibitors observed in preclinical study might be translated to
      the current clinical practice.

PMID- 23127527
TI  - Diagnostic value of EUS elastography in differentiation of benign and malignant
      solid pancreatic masses: a meta-analysis.
AB  - BACKGROUND/AIMS: EUS elastography is a novel technique that can be used for
      distinguishing benign from malignant lymph nodes and focal pancreatic masses.
      However, the studies pertaining to EUS elastography for differential diagnosis of
      solid pancreatic masses have reported widely varied sensitivities and
      specificities. A meta-analysis of all relevant articles was performed to estimate
      the overall diagnostic accuracy of EUS elastography for differentiating benign
      and malignant solid pancreatic masses. METHODS: The literatures were identified
      by searching in PubMed and Embase databases. Two reviewers independently
      extracted the information from the literatures for constructing 2 * 2 table. A
      random-effect model or a fixed-effect model was used to estimate the sensitivity,
      specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic
      odds ratio. A summary receiver operating characteristic curve (SROC) also was
      constructed. Meta-regression and subgroup analysis were used to explore the
      sources of heterogeneity. RESULTS: 13 studies including a total of 1042 patients
      with solid pancreatic masses were selected for meta-analysis. The pooled
      sensitivity and specificity of EUS elastography for differentiating benign and
      malignant solid pancreatic masses were 95% (95% confidence interval [CI], 93%
      96%), 69% (95% CI, 63%-75%), respectively. The area under SROC (AUC) was 0.8695.
      Two significant variables were associated with heterogeneity: color pattern and
      blinding. CONCLUSION: As a less invasive modality, EUS elastography is a
      promising method for differentiating benign and malignant solid pancreatic masses
      with a high sensitivity, and it can prove to be a valuable supplement to EUS-FNA.

PMID- 23127528
TI  - Monitoring of CA19-9 and SPan-1 can facilitate the earlier confirmation of
      progressing pancreatic cancer during chemotherapy.
AB  - BACKGROUND: Measurement of objective response to chemotherapy using imaging
      modalities is sometimes difficult in pancreatic cancer (PC). We aimed to verify
      whether monitoring of serum tumor markers (TMs), namely carcinoembryonic antigen,
      CA19-9, DUPAN-2, SPan-1, can facilitate earlier confirmation of treatment
      failure. METHODS: Monitoring of serum TMs and computed tomography were performed
      every 4 weeks until progression of disease in 90 patients with PC undergoing
      gemcitabine therapy. In Group A (January 2006-October 2007), we analyzed the
      fluctuation rates of TMs with high pretreatment positive rates, and defined the
      criteria of progressive disease under TM monitoring (TM-PD). In Group B (November
      2007-October 2008), we calculated the time to progression (TTP) under this TM-PD
      criteria, which was compared with the TTP under the RECIST criteria. RESULTS:
      CA19-9 and SPan-1 had the highest pretreatment positive rates: 83% and 90%,
      respectively. In Group A (CA19-9, n = 38; SPan-1, n = 36), TM-PD criteria were
      defined as follows: fluctuation rates were >=25% for a month or >=10% for 2
      consecutive months in CA19-9, and >=10% for a month in SPan-1. In Group B (CA19
      9, n = 18; SPan-1, n = 17), under these criteria, one-month earlier confirmation
      of treatment failure was feasible in 61% by CA19-9 and 59% by SPan-1.
      Furthermore, the combination could facilitate this determination in 72% (35/49),
      significantly better than CA19-9 alone (P = 0.004). CONCLUSION: Monitoring of
      serum CA19-9 and SPan-1 is helpful for earlier confirmation of treatment failure
      during gemcitabine therapy in PC.

PMID- 23127529
TI  - A comparative analysis of K-ras mutation and carcinoembryonic antigen in
      pancreatic cyst fluid.
AB  - BACKGROUND/AIMS: Analysis of cystic fluid may be useful in distinguishing between
      benign and malignant cysts which has significant impact on their management. The
      aim of our study was to assess the diagnostic utility of carcinoembryonic antigen
      (CEA) and K-ras gene mutation in pancreatic cysts fluid. METHODS: The study
      included 56 patients with pancreatic cystic fluid collected for analysis. The
      cysts were classified as benign (simple cysts, pseudocysts, serous cystadenoma) -
      39 patients or premalignant/malignant (mucinous cystadenoma, IPMN,
      cystadenocarcinoma) - 17 patients. The patients history, CEA fluid concentrations
      and presence of K-ras mutation were analyzed. RESULTS: CEA were higher in
      patients with malignant cysts (mean levels 238 +/- 12.5 ng/ml; range 32.8-4985
      ng/ml) compared to benign lesions (mean levels 34.5 +/- 3.7 ng/ml; range 3.9-693
      ng/ml; p < 0.001). K-ras mutation correctly classified 11 of 17 patients with
      premalignant/malignant lesions. It was also detected in 1 patient with final
      diagnosis of benign cyst (the sensitivity 64.7% and the specificity 97.4%; p <
      0.01). If CEA and molecular analysis were combined in that cysts with either CEA
      level>45 ng/ml or presence of K-ras mutation, than 16 of 17
      premalignant/malignant cysts were correctly identified (94.1%). CONCLUSION:
      Molecular analysis of pancreatic cyst fluid adds diagnostic value to the
      preoperative diagnosis and should be considered when cyst cytologic examination
      is negative for malignancy.

PMID- 23127530
TI  - The odd case of a small and mucinous-like acinar cell cystoadenocarcinoma of the
      pancreas.

PMID- 23127531
TI  - Successful selective internal radiotherapy (SIRT) in a patient with a malignant
      solid pseudopapillary pancreatic neoplasm (SPN).
AB  - Solid pseudopapillary neoplasms of the pancreas (SPNs, Gruber-Frantz-Tumor) are a
      rare entity representing 1-5% of all exocrine pancreatic tumors. The pseudocystic
      lesions preferentially affect young females <30 years, are mostly benign (~90%)
      and normally present with unspecific symptoms. We describe the case of a 16-years
      old Asian woman that was initially diagnosed with an SPN in the pancreatic head
      with mesenterial and hepatic metastases. After diagnosis, an extensive tumor
      resection was performed including pyloric-preserving pancreatic head resection
      followed by sequential resection of all hepatic metastases. After the patient was
      diagnosed with a hepatic recurrence and high intrahepatic tumor load, we chose a
      multimodal procedure and performed a selective internal radiotherapy (SIRT). Four
      years after SIRT and 10 years after initial diagnosis of metastatic SPN, the
      patient is in a good condition without any evidence for hepatic recurrence. This
      case represents a rare clinical course of a malignant and invasive SPN with an
      exceptionally long survival despite of high initial tumor burden. The selective
      internal radiotherapy is a suitable approach for inducing long-term remissions of
      the strongly vascularized liver metastases.

PMID- 23127532
TI  - Treatment outcome for systemic chemotherapy for recurrent pancreatic cancer after
      postoperative adjuvant chemotherapy.
AB  - OBJECTIVES: A global consensus on how to treat recurrent pancreatic cancer after
      adjuvant chemotherapy with gemcitabine (ADJ-GEM) does not exist. METHODS: We
      retrospectively reviewed the clinical data of 41 patients with recurrences who
      were subsequently treated with chemotherapy. RESULTS: The patients were divided
      into two groups according to the time until recurrence after the completion of
      ADJ-GEM (ADJ-Rec): patients with an ADJ-Rec < 6 months (n = 25) and those with an
      ADJ-Rec >= 6 months (n = 16). The disease control rate, the progression-free
      survival after treatment for recurrence and the overall survival after recurrence
      for these two groups were 68 and 94% (P = 0.066), 5.5 and 8.2 months (P = 0.186),
      and 13.7 and 19.8 months (P = 0.009), respectively. Furthermore, we divided the
      patients with an ADJ-Rec < 6 months into two groups: patients treated with
      gemcitabine (n = 6) and those treated with alternative regimens including
      fluoropyrimidine-containing regimens (n = 19) for recurrent disease. Patients
      treated with the alternative regimens had a better outcome than those treated
      with gemcitabine. CONCLUSIONS: Fluoropyrimidine-containing regimens may be a
      reasonable strategy for recurrent disease after ADJ-GEM and an ADJ-Rec < 6
      months.

PMID- 23127533
TI  - Impact of omission of elective nodal irradiation on treatment outcomes in locally
      advanced pancreatic adenocarcinoma patients treated with definitive concurrent
      chemoradiotherapy.
AB  - BACKGROUND: We evaluated influence of limited-field radiotherapy with no elective
      nodal irradiation (ENI) on outcomes and toxicity profile in patients with locally
      advanced pancreatic adenocarcinoma (LAPAC), treated with definitive concurrent
      chemoradiotherapy (C-CRT). METHODS: Thirty-five patients with histological proof
      of LAPAC underwent 50.4Gy of C-CRT with 5-FU followed by maintenance gemcitabine.
      Target volume included primary tumor and lymph nodes that appeared to be involved
      on either contrast-enhanced computerized tomography or 18F-fluoro-deoxyglucose
      positron emission tomography. RESULTS: No grade 4/5 acute/late toxicity was
      reported at median 15.7 months. Acute hematologic plus non-hematologic grade 3
      toxicity was noted in 10 (28.6%) patients. At long-term, 2 patients (5.7%)
      experienced grade 3 gastric outlet obstructions at 8.7 and 10.9 months,
      respectively. No isolated regional relapses were noted. Median overall-survival
      (OS), progression-free survival (PFS), and locoregional-PFS (LRPFS) were 15.2,
      9.1 and 7.3 months, respectively. Corresponding 1- and 2-year survival estimates
      were 60.0% and 20.0% for OS, 41.9% and 17.4% for LRPFS, and 34.0% and 12.7% for
      PFS, respectively. CONCLUSIONS: Compared to ENI literature, first report of a
      limited-field C-CRT study carried out in Turkey showed that omission of ENI was
      relatively well tolerated without compromising survival and locoregional control
      rates in patients with LAPAC.

PMID- 23127534
TI  - Enhancement of the cytocidal effects of hypotonic solution using a chloride
      channel blocker in pancreatic cancer cells.
AB  - BACKGROUND: Tumor cells exfoliated during surgery for pancreatic cancer can cause
      peritoneal recurrence. Peritoneal lavage with distilled water has been performed
      during surgery, but there have been no systematic studies for its efficacy and no
      experimental data demonstrating the cytocidal effects of distilled water on
      pancreatic cancer cells. This study investigated the cytocidal effects of
      hypotonic shock and enhancement using chloride channel blocker in pancreatic
      cancer cells. METHODS: Three human pancreatic cancer cell lines, KP4-1, PK-1, and
      PK45-H, were exposed to distilled water, and the resultant morphological changes
      were observed under a differential interference contrast microscope connected to
      a high-speed video camera. Analysis of cell volume changes was performed using a
      high-resolution flow cytometer. To investigate the cytocidal effects of water, re
      incubation of cells was performed after exposure to hypotonic solution.
      Additionally, the effects of 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB),
      a Cl(-) channel blocker, on cells during exposure to hypotonic solution were
      analyzed. RESULTS: Video recordings demonstrated that hypotonic shock induced
      cell swelling followed by cell rupture. Measurement of cell volume changes
      indicated that severe hypotonicity increased broken fragments of cancer cells
      within 5 min. Re-incubation experiments demonstrated the cytocidal effects of
      hypotonic shock. In all cell lines, treatment with NPPB increased cell volume by
      inhibiting regulatory volume decreases, which are observed during hypotonic
      shock, and enhanced the cytocidal effects of hypotonic solution. CONCLUSIONS:
      These findings support the efficacy of peritoneal lavage with distilled water for
      pancreatic cancer and suggest that regulation of Cl(-) transport enhances the
      cytocidal effects of hypotonic shock.

PMID- 23127535
TI  - Severe acute pancreatitis is associated with upregulation of the ACE2-angiotensin
      (1-7)-Mas axis and promotes increased circulating angiotensin-(1-7).
AB  - BACKGROUND/OBJECTIVES: Angiotensin-converting enzyme 2 (ACE2), its product
      angiotensin-(1-7) and its receptor Mas may counteract the adverse effects of the
      ACE-angiotensin receptor II-AT(1) axis in many diseases. We examined the
      expression of these novel components of the rennin-angiotensin system in an
      experimental mouse model of severe acute pancreatitis (SAP). METHODS: SAP was
      induced by six intraperitoneal injections of caerulein, and mice were sacrificed
      at 2, 12, 24, 48 and 72 h post disease-induction (normal control group mice were
      sacrificed at 2 h post disease-induction). Tissue and blood were collected for
      biochemical detection, gene and protein expression by qRT-PCR and western blot
      analysis, enzyme-linked immunosorbent assay and immunohistology detection.
      RESULTS: Pancreatic ACE2 gene and protein expression, plasma and pancreatic
      angiotensin-(1-7) levels and Mas receptor gene and protein expression were
      significantly increased (p < 0.05) following SAP induction compared with the
      normal control group. CONCLUSIONS: Severe acute pancreatitis is associated with
      upregulation of the ACE2-angiotensin-(1-7)-Mas axis and promotes increased
      circulating angiotensin-(1-7). These results support the presence of an ACE2
      angiotensin-(1-7)-Mas axis in pancreatitis.

PMID- 23127536
TI  - Probiotic treatment with Probioflora in patients with predicted severe acute
      pancreatitis without organ failure.
AB  - BACKGROUND: We previously demonstrated that probiotic prophylaxis, in patients
      with predicted severe pancreatitis, did not prevent infectious complications but
      unexpectedly increased the risk of bowel ischemia and mortality. The suggestion
      that these negative findings are only observed in the presence of organ failure
      at the start of probiotic treatment has not been confirmed. METHODS: In a
      retrospective analysis, all patients with predicted severe acute pancreatitis
      without initial organ failure admitted to a medium care facility of a teaching
      hospital in Prague from January 2003 to December 2010 were included. All patients
      routinely received probiotic treatment with Probioflora. Total parenteral
      nutrition (TPN) was routinely started and shifted toward total enteral nutrition.
      Infectious complications, mortality and the incidence of bowel ischemia were
      recorded. RESULTS: 99 consecutive patients, mean age 56 years, were included.
      Infectious complications occurred in 42 patients (42%), consisting of bacteremia
      (n = 40), pneumonia (n = 11) and infected necrosis (n = 11). Bowel ischemia was
      detected in two patients (2%). Overall mortality was 8%. CONCLUSION: In this
      retrospective study no apparent positive or negative impact of probiotic
      treatment with Probioflora was demonstrated when administered to patients with
      predicted severe acute pancreatitis without initial organ failure.

PMID- 23127537
TI  - Pancreatic stent migration into the portal vein causing portal vein thrombosis: a
      rare complication of a prophylactic pancreatic stent.
AB  - This report describes the first case of a novel complication of prophylactic
      pancreatic stents used to reduce the risk of post-endoscopic retrograde
      cholangiopancreatography pancreatitis, whereby the stent migrated into the portal
      vein resulting in portal vein thrombosis. We review the literature and discuss
      the potential mechanisms that caused this complication. The approach and prompt
      treatment that resulted in a favorable clinical outcome are described.

PMID- 23127538
TI  - Expanding conceptual frameworks: life course risk modelling for mental disorders.
AB  - Psychiatric epidemiology has made significant contributions to the identification
      of risk factors for mental disorders. Available evidence underscores the
      complexity of the interactions between risk and disease and highlights conceptual
      and methodological challenges particularly in examining risk and disease
      relations beyond the level of simple associations. We propose that a life course
      approach in the study of risk factors for mental disorders, combined with fast
      developing analytical statistical tools, is the most promising avenue towards
      shifting the focus of the field from associations to generating and testing
      aetiological hypotheses. This review presents the basic tenants of life course
      risk modelling, highlighting key examples in the available literature that
      demonstrate the potential of this approach to advance our understanding of the
      trajectories from risk to disease and discusses priorities for future research.

PMID- 23127539
TI  - CareCoor: augmenting the coordination of cooperative home care work.
AB  - OBJECTIVES: The present study aims to augment the network of home care around
      elderly. We investigate the nature of cooperative work between relatives and home
      care workers around elderly persons; present the CareCoor system developed to
      support that work; and report experiences from two pilot tests of CareCoor.
      METHODS: We employed ethnographic fieldwork methods and conducted participatory
      design workshops to throw light on the nature of cooperative home care work, and
      to elicit implications for the design of an IT system that would support the work
      of relatives and home care workers around elderly persons. The design
      implications led to the development of a prototype, called CareCoor, which is
      accessible via a tablet PC and on the Internet. CareCoor was subsequently
      evaluated in two pilot tests. The first lasted a week and included three elderly,
      their next of kin and the affiliated home care workers, while the second test
      lasted for six weeks and involved five elderly people, their next of kin and
      relevant home care workers. RESULTS: In the paper we make three major points,
      namely, (1) home care work is highly cooperative in nature and involves
      substantial coordinative efforts on the part of the actors involved, (2) the
      network of care around elderly can be augmented with new technology that allows
      all members of the network to follow, influence and be a part of the cooperative
      care of the elderly, and (3) CareCoor, the prototype introduced in this study,
      shows promise as it was well received during test and evaluation. CONCLUSION:
      Home care work is increasingly important due to the ageing populations of Europe,
      the USA and large parts of Asia. Home care work between relatives and home care
      workers is inherently a cooperative effort, and can be facilitated and augmented
      by new information technology such as CareCoor. The pilot tests of CareCoor
      revealed promising results and will be further developed and evaluated in a
      larger test.

PMID- 23127540
TI  - Sulfur fumigation, a better or worse choice in preservation of Traditional
      Chinese Medicine?
AB  - Sulfur fumigation (SF) in Traditional Chinese Medicine (TCM) is a highly
      efficient and important traditional preservation method in China. This method has
      generated a great deal of concern and has been disputed in the last few years
      because of its uncertain safety. SF can alter the quality of TCMs by damaging the
      bioactive compounds, changing chemical profiles, and generating detrimental
      exogenous materials. However, SF is still widely used in the herbal medicinal
      industry because of its various benefits, such as its pesticidal and anti
      bacterial effects, easy operation, and low-cost. This review contains the current
      situation, chemical mechanism and reactions during SF, the pharmacological and
      pharmacokinetic research, and the influence of quality caused by SF. In addition,
      a quantification-operation sulfur fumigation device (QOSFD), which can maintain
      the quality of TCMs by controlling the SF processing parameters, has been
      designed and introduced. The key technologies of this device involve controlling
      the O(2) content and the temperature of SO(2) as well as the quantification of
      sulfur in SF. This device can reduce the possibility of reaction between
      bioactive compounds and sulfur/sulfurous acid, as well as control the limitation
      of SO(2) residues. The QOSFD is regarded as a promising preservation technique in
      the field of TCM, medicinal materials, agriculture, and fruit industry.

PMID- 23127541
TI  - Mexico's precursor chemical controls: emergence of less potent types of
      methamphetamine in the United States.
AB  - BACKGROUND: This study examines whether Mexico's controls on ephedrine and
      pseudoephedrine, the two precursor chemicals that yield the most potent form of
      methamphetamine, d-methamphetamine, impacted the prevalence/availability of less
      potent types of methamphetamine in the United States-types associated with the
      alternative precursor chemical P2P. METHOD: Using ARIMA-intervention time series
      analysis of monthly drug exhibits (a prevalence/availability indicator) from the
      System to Retrieve Information from Drug Evidence (STRIDE), we tested whether
      Mexico's controls, which began in 2005, were associated with growth/decline in d
      methamphetamine and growth/decline in P2P-associated, less potent l
      methamphetamine, racemic methamphetamine (a 50:50 ratio of d- and l-isomers), and
      mixed isomer methamphetamine (an unequal ratio of d- and l-isomers). Heroin,
      cocaine and marijuana exhibits were used for quasi-control (01/2000-04/2011).
      RESULTS: Mixed-isomer exhibits constituted about 4% of the methamphetamine
      exhibits before Mexico's controls, then rose sharply in association with them and
      remained elevated, constituting about 37% of methamphetamine exhibits in 2010. d
      Methamphetamine exhibits dropped sharply; l-methamphetamine and racemic
      methamphetamine exhibits had small rises. d-Methamphetamine exhibits partially
      recovered in the US West, but little recovery occurred in the US Central/South.
      Quasi-control series were generally unaffected. CONCLUSION: The US
      methamphetamine market changed. Widespread emergence of less potent
      methamphetamine occurred in conjunction with Mexico's controls. And
      prevalence/availability of the most potent type of the drug, d-methamphetamine,
      declined, a partial recovery in the West notwithstanding. Granting that lower
      potency drugs typically engender less dependence and attendant problems, these
      findings suggest that, following Mexico's controls, the potential harm of a
      sizeable amount of the US methamphetamine supply decreased.

PMID- 23127542
TI  - Elevated gamma band power in humans receiving naloxone suggests dorsal
      periaqueductal and periventricular gray deep brain stimulation produced analgesia
      is opioid mediated.
AB  - BACKGROUND: The midbrain periaqueductal and periventricular gray (PAVG) region is
      important for pain and autonomic modulation. We have previously described changes
      in blood pressure dependent upon dorsal or ventral electrode positioning with
      PAVG deep brain stimulation (DBS), yet controversy exists about whether DBS acts
      via endogenous opioid release. METHOD AND RESULTS: We combined local field
      potential (LFP) recording from PAVG DBS electrodes in humans with naloxone and
      saline infusions to determine whether dorsal and ventral PAVG DBS act through
      opioidergic or other mechanisms. Four awake human subjects were investigated. DBS
      were implanted contralateral to the painful body part. Electrode contact
      positions were mapped using MRI and brain atlas information. Naloxone then saline
      were randomly administered to the blinded subjects and pain rated using a numeric
      pain rating scale at 30s intervals for 3 min. Two subjects received dorsal DBS
      electrodes and two had ventral placements. Significantly elevated gamma frequency
      band (30-90 Hz) power concomitant with pain exacerbation was found with naloxone
      versus both saline and rest in dorsal not ventral PAVG LFPs (p<0.005).
      Significantly elevated delta frequency band (0-4 Hz) power (p=0.001) was seen in
      one ventral PAVG subject with both naloxone and saline infusions. CONCLUSIONS:
      Dorsal PAVG DBS may reduce pain by augmenting endogenous opioid release. Elevated
      gamma oscillations enhance awareness of worsening pain with opioid blockade.
      Ventral PAVG DBS may act by separate possibly autonomic mechanisms. Increased
      delta oscillations indicate a survival rhythm involved in the initiation of
      passive coping responses to homeostatic changes.

PMID- 23127543
TI  - A soy, whey and caseinate blend extends postprandial skeletal muscle protein
      synthesis in rats.
AB  - BACKGROUND & AIMS: Blends of dairy and soy protein are used in commercial sports
      nutrition products; however, no studies have systematically compared blends to
      isolated protein sources and their effects on muscle protein synthesis (MPS).
      Dairy whey protein (WP), soy protein isolate (SP), and two blends (Blend 1 and
      Blend 2) consisting of ratios of 50:25:25 and 25:50:25 for whey:caseinate:soy,
      respectively, were evaluated for their ability to affect MPS. METHODS: Male
      Sprague-Dawley rats were trained to eat 3 meals/day: a 4 g meal at 0700-0720
      hours followed by ad lib feeding at 1300-1400 hours and 1800-1900 hours. After ~5
      days of training, fasted rats were administered their respective 4 g meal at 0700
      0720 hours and an intravenous flooding dose of (2)H5-phenylalanine 10 min prior
      to euthanasia. Individual rats were euthanized at designated postprandial time
      points. Blood and gastrocnemius samples were collected and the latter was used to
      measure mixed muscle protein fractional synthetic rates (FSR). RESULTS: Plasma
      leucine concentrations peaked in all groups at 90 min and were still above
      baseline at 300 min post-meal. FSR tended to increase in all groups post-meal but
      initial peaks of FSR were different times (45, 90 and 135 min for WP or SP, Blend
      1 and Blend 2, respectively). Blend 2 had a significantly higher FSR compared to
      WP alone at 135 min (P < 0.05). CONCLUSIONS: Single source proteins and protein
      blends all enhance skeletal MPS after a meal, however, Blend 2 had a delayed FSR
      peak which was significantly higher than whey protein at 135 min.

PMID- 23127544
TI  - Nasal folliculosebaceous hamartoma with vascular-mesenchymal overgrowth in an
      infant.
AB  - The nasal hamartoma is a rare non-neoplastic malformation or inborn error of
      tissue development, characterized by a mix of several tissue types.
      Folliculosebaceous cystic hamartoma is a distinct type of cutaneous hamartoma. We
      present a 3-month-old male infant who had nasal obstruction and who had a
      diagnosis of nasal folliculosebaceous cystic hamartoma after surgery.

PMID- 23127545
TI  - Grand opening of structure-guided design for novel opioids.
AB  - Twelve years after the publication of the first crystal structure of a G-protein
      coupled receptor (GPCR), experimental crystal structures of the four opioid
      receptor subtypes have made their entrance into the literature in the most
      extraordinary way, that is, all at once. Not only do these crystal structures
      contribute unprecedented molecular details of opioid ligand binding and
      specificity, but they also represent important tools for structure-based
      approaches to guide the discovery of safer and more efficient opioid
      therapeutics. We provide here an overview of these latest breakthroughs in the
      structural biology of GPCRs with a focus on differences and similarities between
      the four opioid receptor structures, as well as their limitations, in the context
      of challenges for translation of this new knowledge from bench to bedside.

PMID- 23127546
TI  - Chromatin remodeling in cancer: a gateway to regulate gene transcription.
AB  - Cancer cells are remarkably adaptive to diverse survival strategies, probably due
      to its ability to interpret signaling cues differently than the normal cells. It
      appears as if cancer cells are constantly sampling, selecting and adapting
      signaling pathways to favor its proliferation. This process of successful
      adaptive evolution eventually renders a retractile nature to therapeutic
      regimens, fueling to the process of cancer progression. Based on plethora of
      available information, it is now evident that multiple signaling pathways
      eventually converge, perhaps, in a tempo-spatial manner, onto DNA template
      dependent dynamic processes. Considering the complexity and packaging of
      eukaryotic genome, this process involves energy-dependent sub-events mediated by
      chromatin remodelers. Chromatin remodeler proteins function as gatekeepers and
      constitute a major determinant of accessibility of accessory factors to
      nucleosome DNA, allowing a wide repertoire of biological functions. And thus,
      aberrant expression or epigenetic modulation of remodeler proteins confers a
      unique ability to cancer cells to reprogram its genome for the maintenance of
      oncogenic phenotypes. Cancer cells can uniquely select a multi-subunit remodeler
      proteome for oncogenic advantage. This review summarizes our current
      understanding and importance of remodeler and chromatin proteins in cancer
      biology and also highlights the paradoxical role of proteins with or without dual
      regulator functions. It is our hope that an in-depth understanding of these
      events is likely to provide a next set of opportunities for novel strategies for
      targeted cancer therapeutics.

PMID- 23127547
TI  - EGFR mediates LPA-induced proteolytic enzyme expression and ovarian cancer
      invasion: inhibition by resveratrol.
AB  - Lysophosphatidic acid (LPA) augments proliferation and metastasis of various
      cancer cells. We recently identified a critical role of the Rho/ROCK pathway for
      LPA-induced proteolytic enzyme expression and cancer cell progression. In the
      present study, we elucidate the underlying mechanisms by which LPA induces Rho
      activation and subsequent cellular invasion, and the reversal of these effects by
      resveratrol. We observed that both Gi and G13 contribute to LPA-induced EGFR
      activation. The activated EGFR in turn initiates a Ras/Rho/ROCK signaling
      cascade, leading to proteolytic enzyme secretion. Further we provide evidence
      that resveratrol inhibits EGFR phosphorylation and subsequent activation of a
      Ras/Rho/ROCK signaling. Therefore, we demonstrate a mechanistic cascade of LPA
      activating EGFR through Gi and G13 thus inducing a Ras/Rho/ROCK signaling for
      proteolytic enzyme expression and ovarian cancer cell invasion, as well as
      interference of the cascade by resveratrol through blocking EGFR phosphorylation.

PMID- 23127548
TI  - [One step surgery for severe African endocrine exophtalmia: clinical case].
AB  - INTRODUCTION: The association hyperthyroidism-exophtalmia is pathognomonic of the
      Graves disease. Classically, the treatment is based on a pluridisciplinary step
      by-step approach with a precise chronology. In some African places, these optimal
      conditions are not present. When confronted to such particular situations, it can
      be proposed to treat surgically at the same time the endocrine disease and the
      ophthalmologic complications. OBSERVATION: The authors report the case of a 42
      year-old women suffering of a great thyreotoxic goiter with severe bilateral
      exophtalmia, treated by thyroidectomy and orbital decompression in the same
      session with a good result after 18 months. DISCUSSION: This non-conventional
      approach can be useful in particular situations when the medical environment is
      not optimal. It permits the radical treatment of their disease and improves the
      prognosis of patients with poor capacities for survey.

PMID- 23127549
TI  - Influence of the STAT3 genetic variants in the susceptibility to psoriatic
      arthritis and Behcet's disease.
AB  - OBJECTIVE: Signal-transducer and activator of transcription protein 3 (STAT3)
      gene encodes a transducer and transcription factor that plays an important role
      in many cellular processes such as cell growth, apoptosis and immune response.
      Several STAT3 genetic variants have been associated to different autoimmune
      diseases. Our aim was to reveal the possible STAT3 influence in other immune
      mediated diseases such as psoriatic arthritis (PsA) and Behcet disease (BD).
      METHODS: The STAT3 rs744166 and rs2293152 polymorphisms were genotyped using
      predesigned TaqMan(r) assays in a total of 335 PsA patients, 217 BD patients, and
      1844 ethnically matched healthy controls of Spanish Caucasian origin. RESULTS: A
      statistically significant association of the STAT3 rs744166(*)G allele with PsA
      was observed (P-value=1.36*10(-3), OR 1.35). The detected effect was more evident
      when the rs744166(*)GG homozygote frequencies were compared between PsA patients
      and controls (genotype P-value=9.77*10(-5), OR 1.82). In contrast, the allele and
      genotypic distributions of rs744166 polymorphism showed no significant
      differences between patients with BD and control subjects (allelic P-value=0.80,
      OR 1.03). Additionally, no evidence of association was detected between the
      rs2293152 genetic variant and both studied diseases. CONCLUSION: Our results
      suggest for the first time that the STAT3 gene might be involved in PsA but not
      in Behcet's disease predisposition.

PMID- 23127550
TI  - HLA-G haplotype structure shows good conservation between different populations
      and good correlation with high, normal and low soluble HLA-G expression.
AB  - HLA-G molecule has considerable impact in various clinical fields, therefore many
      studies attempted to predict its expression based on HLA-G genotype. These
      studies have focused on polymorphisms in either the coding region or in one of
      the two untranslated regions (UTR) of the gene. The aim of our study was to
      determine if HLA-G haplotype defined based on SNPs 5' and 3'UTR could be used to
      predict soluble HLA-G expression in unstimulated individuals. Our findings showed
      that HLA-G haplotype structure was well conserved between distant populations and
      that the defined haplotypes were correlated with high, normal and low HLA-G
      soluble secretors. In conclusion, we showed that this genotyping strategy based
      on the use of a few selected SNPs rather than isolated SNP analysis allows
      reliable HLA-G expression in all populations. This strategy could be useful in a
      number of clinical settings, e.g., predicting graft compatibility immunogenetic
      laboratories.

PMID- 23127551
TI  - The polymorphism of Knops blood group system in Korean population and their
      relationship with HLA system.
AB  - The main purpose of this report is to provide baseline gene frequencies of Knops
      blood group in the complement receptor 1 gene (CR1) in Korean population. In
      addition, possible relationship between the CR1 polymorphism and HLA
      specificities were studied, because the two systems had principal importance in
      immunity. CR1, which contains Knops antigens, was investigated by PCR-direct
      sequencing from 238 cord blood from Koreans. HLA data was archived from the
      enrolled cord blood units. Among the 7 SNPs, only 4843 (for KCAM antigen) and
      4223 (for Yk(a)) nucleotide positions showed polymorphism. The genotype
      frequencies of KCAM were A/A (62.2%), A/G (33.2%), and G/G (4.6%); Yk(a) were C/C
      (29.4%), C/T (50%), and T/T (20.6%). KCAM (A/A) associated with HLA-DRB1(*)13
      (p=0.003, P(c)=0.0513); KCAM (G/G) with HLA-A(*)30 (p<0.001, P(c)=0.0012). The
      Knops blood group system in Korean population has no diversity, except SNPs for
      KCAM and Yk(a), and the genotype of KCAM related with specific HLA alleles.

PMID- 23127552
TI  - Mental health and aging initiative: intervention component effects.
AB  - INTRODUCTION: The objective of this investigation is to evaluate the Mental
      Healthiness and Aging Initiative (MHAI) intervention. The MHAI was created to
      promote awareness and knowledge about mental health/substance (MH/SA) use and
      aging issues in rural Kentucky, USA, due to limitations in formal and informal
      mental health care and treatment resources as a result of multilevel barriers in
      rural regions and effects on health, wellbeing and quality of life. METHODS: This
      investigation took place between 2010 and 2011 in two rural counties in Kentucky.
      Participants from two counties were recruited through an email solicitation sent
      to Kentucky cooperative extension agents (university-affiliated community
      liaisons). Individuals participated in a two-hour intervention session covering
      facts and information, application exercises, and community tools for addressing
      late-life mental health and substance abuse. Effectiveness was evaluated by
      examining changes in attitudes and knowledge about MH/SA and aging from pre-test
      to post-test and again 3 months and 6 months later. The evaluation survey
      examined mental health and substance abuse awareness (six questions) and
      knowledge (13 questions) and was previously piloted and designed for the current
      study ensuring face validity. Seven individual linear mixed models were analyzed
      using each of the six awareness questions and an additional model using an
      aggregate score across the knowledge questions representing the total percent
      correct for knowledge questions. RESULTS: The participating sample (n=55) was
      65.35 years of age on average, with the majority being female (85%), white
      (100%), married (69%), living with a spouse/partner only (68%), high school
      educated (57%) and having a total household income averaging US$44,199. The
      findings indicated sustained improvement in awareness and knowledge about MH/SA
      and aging. Results also indicated that there is a need to improve maintenance of
      knowledge regarding older adult alcohol consumption risk, clinical provider
      communication about mental health, identifying/recognizing mental health
      problems, and older adult retention of their mental abilities based on long-term
      retention rates. These indicators had below 90% correctness at 6 months, despite
      having 90%+ accuracy at post-assessment, immediately after the intervention
      administration. CONCLUSIONS: This study demonstrates that community interventions
      for MH/SA awareness and knowledge are effective within majority rural regions. As
      currently designed, implementing the MHAI intervention program is feasible.
      Evidence from the current study indicates that community residents (including
      rural individuals) can be recruited to participate in a program about MH/SA and
      aging, and as an outcome have increased awareness and knowledge about MH/SA and
      aging. Future research will need to explore how to utilize MHAI-type intervention
      programs to a point where the mental health of rural adults can be improved.
      Specifically, further investigation is needed to examine whether community mental
      health awareness interventions, such as the MHAI intervention program, can lead
      to earlier detection of MH/SA issues among older adults and increase treatment
      rates. If so, community mental health workers and facilities can expect such
      interventions to increase local residents' awareness of their services and
      likelihood of utilizing mental health services. Future research needs to enhance
      generalizability and ensure that improved knowledge and awareness translates into
      improved mental health in rural regions.

PMID- 23127553
TI  - Genetics of behavioural adaptation of livestock to farming conditions.
AB  - Behavioural adaptation of farm animals to environmental changes contributes to
      high levels of production under a wide range of farming conditions, from highly
      controlled indoor systems to harsh outdoor systems. The genetic variation in
      livestock behaviour is considerable. Animals and genotypes with a larger
      behavioural capacity for adaptation may cope more readily with varying farming
      conditions than those with a lower capacity for adaptation. This capacity should
      be exploited when the aim is to use a limited number of species extensively
      across the world. The genetics of behavioural traits is understood to some
      extent, but it is seldom accounted for in breeding programmes. This review
      summarizes the estimates of genetic parameters for behavioural traits in cattle,
      pigs, poultry and fish. On the basis of the major studies performed in the last
      two decades, we focus the review on traits of common interest in the four
      species. These concern the behavioural responses to both acute and chronic
      stressors in the physical environment (feed, temperature, etc.) and those in the
      social environment (other group members, progeny, humans). The genetic strategies
      used to improve the behavioural capacity for adaptation of animals differ between
      species. There is a greater emphasis on responses to acute environmental stress
      in fish and birds, and on responses to chronic social stress in mammals.

PMID- 23127555
TI  - Neutrophils come of age in chronic inflammation.
AB  - Neutrophils have long been known to participate in acute inflammation, but a role
      in chronic inflammatory and autoimmune diseases is now emerging. These cells are
      key players in the recognition and elimination of pathogens, but they also sense
      self components, including nucleic acids and products of sterile tissue damage.
      While this normally contributes to tissue repair, it can also lead to the release
      of highly immunogenic products that can trigger and/or amplify autoimmune
      pathogenic loops. Understanding the mechanisms that underlie neutrophil
      activation, migration, survival and their various forms of death in health and
      disease might provide us with new approaches to treat chronic inflammatory
      conditions.

PMID- 23127556
TI  - HuR posttranscriptionally regulates early growth response-1 (Egr-1) expression at
      the early stage of T cell activation.
AB  - T cell activation depends on appropriate and precise regulation of gene
      expression. Here we find that rapidly translocated RNA-binding protein HuR, forms
      messenger ribonucleoprotein (mRNP) complexes with transiently expressed mRNAs
      encoding early-response transcription factors, including c-Fos, c-Jun, and Egr-1.
      Knockdown and overexpression assays demonstrated that proper posttranscriptional
      control of Egr-1 expression requires HuR-mediated translation control. Further
      analysis showed that the Egr-1 3'UTR, which contains AU-rich elements (AREs) and
      interacts directly with HuR, suppresses reporter gene expression and mediates
      posttranscriptional regulation of Egr-1 by HuR. These findings underscore an
      essential role for HuR in regulating early events during T cell activation.

PMID- 23127558
TI  - Depletion of CSN5 inhibits Ras-mediated tumorigenesis by inducing premature
      senescence in p53-null cells.
AB  - The mammalian COP9 signalosome (CSN) complex is involved in cell transformation,
      but its molecular mechanism remains undetermined. Here we show that disruption of
      the fifth component (CSN5) prevented the formation of tumors by p53-null cells
      transformed with an active form of Ras in subcutaneously injected mice. Depletion
      of CSN5 suppressed cell proliferation, and induced premature senescence
      characterized by upregulation of senescence-associated-beta-galactosidase
      activity and increased expression of CDK inhibitors. CSN5-depleted cells
      exhibited enhanced activation of the PI3 kinase-Akt pathway, and chemical
      inhibition of this pathway reduced the level of senescence. Thus, CSN5 is
      suggested to be a novel target in cancer therapy and for drugs against tumor
      cells harboring mutated p53.

PMID- 23127559
TI  - Evidence for zinc and cadmium binding in a CDF transporter lacking the
      cytoplasmic domain.
AB  - Cation diffusion facilitators (CDFs) have been described as requiring the C
      terminal cytoplasmic domain for their function. With the identification of
      smaller proteins lacking the cytoplasmic portion but displaying sequential
      characteristics of CDFs, this assumption should be reconsidered. Here we describe
      the results showing that the MmCDF3, a 23-kDa protein lacking a C-terminal
      domain, interacts selectively with zinc and cadmium. Isothermal titration
      calorimetry (ITC) binding results indicate that the truncated CDF may have an
      alternative means of acquiring ions from the cytoplasm in the form of an extended
      N-terminus, a feature common to putative cation efflux proteins of a similar
      size.

PMID- 23127557
TI  - Effects of the loss of the axial tyrosine ligand of the low-spin heme of MauG on
      its physical properties and reactivity.
AB  - MauG catalyzes posttranslational modifications of methylamine dehydrogenase to
      complete the biosynthesis of its protein-derived tryptophan tryptophylquinone
      (TTQ) cofactor. MauG possesses a five-coordinate high-spin and a six-coordinate
      low-spin ferric heme, the latter with His-Tyr ligation. Replacement of this
      tyrosine with lysine generates a MauG variant with only high-spin ferric heme and
      altered spectroscopic and redox properties. Y294K MauG cannot stabilize the bis
      Fe(IV) redox state required for TTQ biosynthesis but instead forms a compound I
      like species on reaction with peroxide. The results clarify the role of Tyr
      ligation of the five-coordinate heme in determining the physical and redox
      properties and reactivity of MauG.

PMID- 23127560
TI  - Feasibility of delivering mesenchymal stem cells via catheter to the proximal end
      of the lesion artery in patients with stroke in the territory of the middle
      cerebral artery.
AB  - Stem cell-based therapy shows great potential in stroke patients. Intra-artery
      infusion exhibits greater biological distribution compared to intravenous
      delivery. In addition, umbilical cord mesenchymal stem cells (UCMSCs) have
      several advantages compared with other types of stem cells. The aim of this study
      was to evaluate the safety and efficacy of UCMSCs delivered by a catheter to a
      near lesion site for treatment of an infarction in the middle cerebral artery
      territory. Four patients with stroke (three with ischemic and one with
      hemorrhagic stroke) in the middle cerebral artery territory were recruited in
      this study. One single dose of 2 * 10(7) UCMSCs was infused within 20 min via
      catheterization in the M1 segment of the middle cerebral artery. The safety and
      efficacy of this approach were assessed during the in-hospital and 6-month follow
      up evaluation. The cell delivery was successfully performed in all of the
      patients, and no major accidents (stroke or death) were observed. Moreover, no
      fever or rash was reported. After cellular therapy, two of the three ischemic
      stroke patients demonstrated improved muscle strength. The improvement of the
      modified Rankin scale was observed in two patients, both of whom suffered from
      ischemic stroke at 90 and 180 days after the stem cell therapy. The hemorrhagic
      stroke patient failed to demonstrate improved muscle strength and did not amend
      his daily activities. Intra-artery delivery of UCMSCs via catheterization was a
      feasible and safe approach and may improve the neurological function of ischemic
      stroke patients with the middle cerebral artery territory infarcts. 

PMID- 23127561
TI  - Impact of travel on the seroprevalence of hepatitis A in children.
AB  - BACKGROUND: Recent data about hepatitis A virus (HAV) seroprevalence in
      industrialized countries and the impact of travels to endemic areas are sparse or
      absent, particularly for children. OBJECTIVE: To determine the impact of travel
      to endemic areas on HAV seroprevalence and estimate the overall HAV
      seroprevalence in children in France. To identify risk factors for positive HAV
      serologic results. STUDY DESIGN: This prospective multicentre cross-sectional
      seroprevalence study took place in eight paediatric emergency units throughout
      France. Children 1-16 years of age following all inclusion and exclusion criteria
      were included. Demographic, socioeconomic, and travel data were prospectively
      collected with a standardized questionnaire before measurement of specific HAV
      antibodies. HAV seroprevalence was determined and its association with diverse
      variables assessed by univariate and multivariate analyses. RESULTS: 430 children
      were included, of whom 116 had travelled to endemic areas. The HAV seroprevalence
      in the overall population was 5% (95%CI, 3-7) and was higher among the travellers
      (12% [95%CI, 6-18]) than among the others (2% [95%CI, 0-3]), OR=7.0 [95%CI, 2.6
      18.8]. Risk factors identified for positive serologic results for HAV were travel
      to an endemic area >7 days (adjusted OR [aOR]=4.3 [95%CI, 1.5-12]), age of 14-16
      years (aOR=7.7 [95%CI, 1.6-38.3]) and mother's birth in an endemic area (aOR=5.2
      [95%CI, 1.8-14.8]). CONCLUSION: Statistical evidence showed that travel to
      endemic areas and parents' place of birth both play a role in HAV serologic
      results in children with a significant difference of HAV seroprevalence between
      traveller and non-traveller children in France.

PMID- 23127562
TI  - Emergence of Dengue virus 4 genotypes II b and I in the city of Rio de Janeiro.

PMID- 23127563
TI  - Strong correlation between tax and HBZ mRNA expression in HAM/TSP patients:
      distinct markers for the neurologic disease.
AB  - BACKGROUND: HTLV-1 proviral load is a risk marker for HAM/TSP, but it is
      insufficient to determine the disease outcome. HTLV-1 Tax and HBZ proteins have
      been implicated in HAM/TSP pathogenesis in inducing cell proliferation and
      cytotoxic T lymphocytes response. OBJECTIVES: To quantify the expression of tax
      and HBZ mRNA in asymptomatic carriers (AC) and HAM patients, and to investigate
      their association with HAM/TSP. STUDY DESIGN: We quantified the expression of
      HTLV-1 tax and HBZ mRNA in 37 AC and 26 HAM patients classified according to
      proviral load as low (AC(L) and HAM(L): <1% infected cells) or high (AC(H) and
      HAM(H): >1%). RESULTS: The AC(L) subgroup showed the lowest frequency of
      individuals expressing tax mRNA in comparison with AC(H), HAM(L) and HAM(H), and
      tax mRNA load normalized by proviral load was significantly lower in the AC(L).
      In turn, normalized HBZ mRNA expression was similar in all subgroups. Both tax
      and HBZ mRNA expression were moderately correlated with proviral load in AC
      (r=0.6, p<0.001) and were weaker in HAM (r=0.4, p<0.05). In contrast, the
      correlation between tax and HBZ mRNA load was moderate in AC (r=0.5, p=0.001) and
      was much stronger in HAM (r=0.8, p<0.001). In addition, HBZ mRNA load, but not
      tax, was significantly associated with motor disability in HAM patients
      (p=0.036). CONCLUSIONS: The expression of tax mRNA seems to be best to estimate
      the risk of HAM/TSP, whereas HBZ mRNA appears to be a surrogate marker to disease
      progression, indicating that they have important but distinct roles in HAM/TSP
      pathogenesis.

PMID- 23127564
TI  - C-type natriuretic peptide specifically acts on the pylorus and large intestine
      in mouse gastrointestinal tract.
AB  - C-type natriuretic peptide (CNP) exerts its main biological effects by binding to
      natriuretic peptide receptor B (NPR-B), a membrane-bound guanylyl cyclase
      receptor that produces cyclic guanosine monophosphate (cGMP). CNP is known to
      cause gastrointestinal (GI) smooth muscle relaxation. Experimental evidence
      suggests a connection between CNP signaling and GI function, with reactive
      regions in the GI tract possibly affecting transit; however, this relation has
      not yet been conclusively shown. Here, we show that CNP plays important region
      specific roles in the GI tract of mice. We found that treatment with CNP (1 or 2
      mg/kg) increased transient cGMP production in the pylorus, colon, and rectum,
      with the higher dose (2 mg/kg) enhancing gastric emptying in mice; this increase
      in cGMP levels was however absent in NPR-B-deficient short-limbed dwarfism (SLW)
      mouse. Furthermore, we found that NPR-B is highly expressed in the pylorus,
      colon, and rectum, being localized to nerve fibers and to the nuclei and
      cytoplasm of smooth muscle cells of the GI tract and blood vessels. Our in vivo
      findings showed that NPR-B-mediated cGMP production after CNP administration
      specifically acted on the pylorus, colon, and rectum and contributed to gastric
      emptying. CNP may thus be a potential therapeutic agent for GI motility/transit
      disorders such as ileus and pyloric stenosis.

PMID- 23127565
TI  - Twin database of the secondary school attached to the Faculty of Education of the
      University of Tokyo: lifecourse database of twins.
AB  - This article profiles the historical twin databases of the secondary education
      school attached to the Faculty of Education at the University of Tokyo. The
      school was established in 1948. Every year, about 50 pairs of twins of all sex
      and zygosity combinations and aged 11-12 years take an examination, and about 10
      20 pairs are admitted based on the results. Three data sets exist: one for
      applicants (11-12 years), one for junior and senior high school students (12-18
      years), and one for graduates (18-79 years). Record linkage of these three
      databases should facilitate several important research projects; for example, the
      lifecourse genetic epidemiologic studies and verification of so-called
      developmental origin of health and disease hypothesis.

PMID- 23127566
TI  - A new hepatotoxic triterpenoid ketone from Curculigo orchioides.
AB  - To investigate hepatotoxic constituents, a new cycloartane-type triterpenoid
      ketone together with four known components was isolated from rhizomes of
      Curculigo orchioides. The structures of five compounds were elucidated on the
      basis of spectroscopic methods, including 1D and 2D NMR, and single-crystal X-ray
      diffraction analysis. Their hepatotoxicity effects in human hepatic cell line HL
      7702 were tested for the first time.

PMID- 23127567
TI  - Nerium oleander derived cardiac glycoside oleandrin is a novel inhibitor of HIV
      infectivity.
AB  - We evaluated the effectiveness of AnvirzelTM, an aqueous extract of Nerium
      oleander on HIV infection of human peripheral blood mononuclear cells. Oleandrin,
      the principle cardiac glycoside (CG) in AnvirzelTM has been shown to exhibit anti
      cancer properties but its efficacy against HIV is unknown. Treatment with
      AnvirzelTM significantly reduced the infectivity of virus produced from infected
      cells without any change in the total amount of virus produced. This is in
      contrast to treatment with AZT, a potent inhibitor of HIV replication that has
      been shown to significantly reduce virus production. Relative to untreated
      cultures, virus in cultures treated with oleandrin had significantly reduced
      expression of the envelope protein gp120, the sole determinant of virus
      infectivity, suggesting a novel mechanism underlying the impaired infectivity.
      These results support the potential utility of the Nerium oleander aqueous
      extract, containing the CG oleandrin as a novel candidate anti-HIV therapeutic.

PMID- 23127568
TI  - Characterization of extended-spectrum beta-lactamase (ESBL)-carrying plasmids and
      clones of Enterobacteriaceae causing cattle mastitis in France.
AB  - Extended-spectrum beta-lactamases (ESBLs) have become widespread enzymes in food
      producing and companion animals worldwide. However, in cattle mastitis, a major
      cause of economic loss in the dairy industry, ESBL-producers were rarely
      described. In this study, from a collection of 1427 Escherichia coli and
      Klebsiella pneumoniae isolates causing clinical mastitis in France, we report
      0.4% (6/1427) of the isolates carrying an ESBL gene. These six isolates were
      genetically unrelated and recovered over a 3-year period of time. The bla(CTX-M
      14) gene was found in 4/6 isolates, and was predominantly located on F2:A-:B-
      IncFII plasmids. The bla(CTX-M-1) IncI1/ST3, which is widespread in various
      animal species in France, was found as well. Interestingly, among the five E.
      coli isolates, the ST23 and ST58 clones were found twice, together with the ST10
      clone, all of which were previously found as ESBL-carriers in humans. Despite the
      very limited number of ESBL-producers recovered, this study shows a surprisingly
      low molecular diversity of the strains causing mastitis in France with respect to
      ESBL genes, plasmids and clones. Further work is needed to understand the major
      driving forces of the ESBL epidemiology in animals, including for different
      infections within the same animal species.

PMID- 23127569
TI  - Cannabidiol exhibits anxiolytic but not antipsychotic property evaluated in the
      social interaction test.
AB  - Cannabidiol (CBD), a non-psychotomimetic compound of the Cannabis sativa, has
      been reported to have central therapeutic actions, such as antipsychotic and
      anxiolytic effects. We have recently reported that Spontaneously Hypertensive
      Rats (SHRs) present a deficit in social interaction that is ameliorated by
      atypical antipsychotics. In addition, SHRs present a hyperlocomotion that is
      reverted by typical and atypical antipsychotics, suggesting that this strain
      could be useful to study negative symptoms (modeled by a decrease in social
      interaction) and positive symptoms (modeled by hyperlocomotion) of schizophrenia
      as well as the effects of potential antipsychotics drugs. At the same time, an
      increase in social interaction in control animals similar to that induced by
      benzodiazepines is used to screen potential anxiolytic drugs. The aim of this
      study was to investigate the effects of CBD on social interaction presented by
      control animals (Wistar) and SHRs. The lowest dose of CBD (1mg/kg) increased
      passive and total social interaction of Wistar rats. However, the hyperlocomotion
      and the deficit in social interaction displayed by SHRs were not altered by any
      dose of CBD. Our results do not support an antipsychotic property of cannabidiol
      on symptoms-like behaviors in SHRs but reinforce the anxiolytic profile of this
      compound in control rats.

PMID- 23127570
TI  - DRD4 gene and obsessive compulsive disorder: do symptom dimensions have specific
      genetic correlates?
AB  - INTRODUCTION: The dopamine D4 receptor (DRD4) is a promising candidate gene in
      obsessive compulsive disorder (OCD). A 48-bp variable number of tandem repeats
      (VNTR) sequence in exon 3 has been studied previously, and alleles containing 2
      11 repeats (2R-11R) have been identified. We investigated the association of DRD4
      VNTR polymorphism with OCD and its relationship with various clinical parameters
      (age of onset, gender, family history, co-morbidity, factor-analyzed symptom
      dimensions and insight). METHODOLOGY: One hundred and seventy three South Indian
      OCD patients (DSM-IV) recruited from a specialty OCD clinic were evaluated using
      the Yale-Brown obsessive compulsive scale (YBOCS), YBOCS item-11 for insight,
      Mini International Neuropsychiatric Interview (MINI) plus, tic disorder
      subsection of the MINI-KID and Clinical Global Impression scale. 201 healthy
      controls were evaluated using MINI plus. All subjects were genotyped for the DRD4
      VNTR polymorphism. RESULTS: Genotype frequencies did not deviate significantly
      from the Hardy-Weinberg equilibrium. Case-control association analysis revealed
      that the 7R allele frequency was significantly greater in OCD patients than
      controls. This difference was restricted to the women subsample when performing
      the gender sub-analysis. Among other clinical variables examined, factor 3
      (symmetry) was associated with presence of 2R allele. Linear regression analysis
      confirmed the association of symmetry dimension with the 2R allele (Beta=0.23,
      t=2.96, p=0.004, CI=0.19-0.95). CONCLUSIONS: Our data provides further evidence
      that DRD4 VNTR polymorphism is associated with OCD. Furthermore, the presence of
      the 2R allele was significantly associated with the symmetry dimension. This
      dimension may represent a more homogeneous subtype of OCD with a genetic
      etiology.

PMID- 23127571
TI  - Hypoxaemia in patients with pulmonary arterial hypertension during simulated air
      travel.
AB  - BACKGROUND: Recent air travel recommendations suggest patients with precapillary
      pulmonary hypertension (PCPH) in New York Heart Association (NYHA) functional
      class 3 and 4 should have in-flight oxygen without the need for pre-flight
      testing. However it remains unclear as to how best to determine patients fitness
      to fly. METHODS: This study (i) investigates the effect of hypoxic challenge
      testing (HCT) on the arterial oxygen levels in a cohort of 36 patients with PCPH
      and (ii) compares the relative frequency with which FC and HCT predict the
      requirement for in-flight oxygen. RESULTS: The degree of arterial hypoxaemia
      induced by HCT (fall in partial pressure of oxygen in arterial blood (PaO(2))
      2.36 kPa, 95% CI 2.06-2.66 kPa) was similar to the drop observed in other
      published studies of chronic respiratory diseases. Following current air travel
      recommendations based on FC, 25 patients of the cohort would require in-flight
      oxygen whilst 10 subjects failed the HCT. Fourteen subjects had flown post
      diagnosis. Of these, nine subjects should have had in-flight oxygen based on FC
      but were asymptomatic without. Also one who passed the HCT had developed symptoms
      during the flight whilst three who failed the HCT were asymptomatic flying
      without in-flight oxygen. CONCLUSIONS: Hypoxaemia induced by simulated air travel
      in patients with PCPH is similar to that seen in published studies of patients
      with other chronic respiratory diseases. HCT failed to predict correctly who had
      developed symptoms during an aircraft flight in a significant minority of the
      study subjects. Similarly guidelines based on functional class result in a major
      increase in the proportion of patients being advised to use oxygen, many of whom
      had been asymptomatic on previous flights without it. More work is required to
      improve prediction of need for in-flight oxygen in patients with PCPH.

PMID- 23127572
TI  - The role of vascular endothelial growth factor-D in diagnosis of
      lymphangioleiomyomatosis (LAM).
AB  - BACKGROUND: Definite diagnosis of lymphangioleiomyomatosis (LAM) depends on
      either transbronchial lung biopsy or video-assisted thoracic surgery, unless
      there is a history of chylothorax, kidney angiomyolipoma (AML), or tuberous
      sclerosis complex (TSC). Vascular endothelial growth factor-D (VEGF-D) was
      recently considered as a novel diagnostic marker for LAM. Herein, we evaluated
      diagnostic value of serum VEGF-D in LAM patients. METHODS: Serum samples were
      obtained from 78 cases of LAM (50 definite and 28 probable LAM based on European
      Respiratory Society guidelines), and 40 healthy female volunteers. VEGF-D was
      measured using enzyme-linked immunosorbant assay according to product instruction
      (R&D). RESULTS: Serum VEGF-D was significantly increased in definite LAM group,
      compared with that of health control (median: 3841.9 pg/mL vs 405.5 pg/mL
      respectively, p < 0.001). The optimal cut-off point for definite LAM diagnosis
      was 850.7 pg/mL. In probable LAM group, the majority of patients (92.9%) had
      serum VEGF-D level over 850.7 pg/mL. The serum levels of VEGF-D in LAM patients
      with pulmonary cystic lesions only were lower than that in patients with any of
      evidences of AML, chylous effusions, adenopathy, lymphangioleiomyomas, or TSC,
      but higher than that in the health control. In addition, VEGF-D levels were
      correlated with disease severity measured as LAM CT grade, and presentations of
      chylous effusions and/or lymphatic involvement (p < 0.05). CONCLUSION: Serum VEGF
      D should be added to the current diagnosis algorithm to enhance definitive
      diagnosis for LAM.

PMID- 23127573
TI  - Association of heart diseases with COPD and restrictive lung function--results
      from a population survey.
AB  - INTRODUCTION: Few studies have explored the association of COPD, based on GOLD
      definition, with heart diseases. The relationship between restrictive lung
      function impairment and heart diseases is still poorly studied on a population
      level. OBJECTIVES: To explore the association of COPD and restrictive lung
      function impairment, respectively, with heart diseases in the general population.
      DESIGN: This is a cross-sectional study of 642 randomly selected 22- to 72-year
      old subjects in northern Sweden. COPD was defined according to GOLD. Restrictive
      lung function was defined as pre-bronchodilator FVC <80% of predicted value and
      FEV(1)/FVC >=0.7. RESULTS: The prevalence of ischemic heart disease was 4% in
      subjects with normal spirometry, 13% in subjects with COPD, and 21% in those with
      restrictive lung function. The prevalence of heart diseases increased with COPD
      severity. On the other hand, the prevalence of COPD was particularly high in the
      group reporting myocardial infarction. In subjects reporting different heart
      diseases, the prevalence of restrictive lung function was high. In multivariate
      analyses including age, sex, smoking habits, family history of obstructive airway
      disease, body mass index, and socio-economic status as independent variables,
      COPD was associated with ischemic heart disease (odds ratio [OR] 2.61; 95%
      confidence interval [CI] 1.12-6.08) and ischemic heart disease with COPD (OR
      2.40; 95% CI 1.03-5.61). CONCLUSION: The study shows a strong association between
      COPD and cardiovascular diseases and indicates a strong association between
      restrictive lung function and heart diseases. Both obstructive and restrictive
      lung function impairments were common among subjects with heart diseases and vice
      versa.

PMID- 23127574
TI  - Endoscopic resection of sessile colon polyps.

PMID- 23127575
TI  - Peroral cholangioscopy: diagnostic and therapeutic applications.

PMID- 23127576
TI  - Sleep parameters from actigraphy and sleep diary: is the agreement important for
      sleep study?

PMID- 23127577
TI  - Behavioural hyperventilation as a novel clinical condition associated with
      central sleep apnoea: a report of three cases.
AB  - Central sleep apnoea (CSA) is a disorder characterised by repetitive episodes of
      decreased ventilation due to complete or partial reduction in the central neural
      outflow to the respiratory muscles. Hyperventilation plays a prime role in the
      pathogenesis of CSA. Chronic heart failure and dwelling at high altitude are
      classical conditions in which CSA is induced by hyperventilation.
      Hyperventilation syndrome (HVS) is a prevalent behavioural condition in which
      minute ventilation exceeds metabolic demands, resulting in haemodynamic and
      chemical changes that produce characteristic dysphoric symptoms. HVS is
      frequently caused by anxiety disorders and panic attacks. Until now, medical
      literature has focussed primarily on daytime symptoms of behavioural
      hyperventilation. It is currently unknown how this condition may affect sleep.
      Three cases are reported in which behavioural hyperventilation was associated
      with occurrence of significant central sleep apnoea, which was not present during
      normal tidal breathing in steady sleep. Therefore, behavioural hyperventilation
      should be added to the list of known clinical conditions associated with CSA.

PMID- 23127578
TI  - A step out of the dark: improving the sleep medicine knowledge of trainees.
AB  - OBJECTIVE: Over 40-million Americans are undiagnosed, misdiagnosed, or untreated
      for sleep disorders. Despite the growing need to integrate sleep medicine
      knowledge into the medical education curriculum, educational leaders have
      struggled to incorporate contemporary medical topics such as sleep medicine into
      the already packed curricula. We set out to examine the efficacy of an online,
      self-paced, sleep medicine learning module as an educational tool for medical
      students. METHODS: We studied 87 Johns Hopkins medical students. Participants
      were randomly assigned to the sham module (SM, n=40) or learning module (LM,
      n=47). The efficacy of the tool was assessed based on changes in performance (pre
      and post-module completion) on a validated sleep knowledge questionnaire (the
      Dartmouth Sleep Knowledge and Attitude Survey). RESULTS: Improvement in overall
      sleep knowledge, as measured by the Dartmouth Sleep Knowledge and Attitude
      Survey, was significantly higher in the LM group compared to the SM group
      (F(1,84)=9.71, p<.01, eta(2)=0.10). Although the SM group's improvement was
      significantly lower than the LM group, within-subject comparisons did show
      improvement from their pre- to post-assessment scores as well. CONCLUSION: A self
      paced learning module is an effective educational tool for delivering sleep
      medicine knowledge to medical students.

PMID- 23127579
TI  - Carotid artery atherosclerosis and sleep disordered breathing in healthy elderly
      subjects: the Synapse cohort.
AB  - BACKGROUND: Sleep-disordered breathing (SDB) has emerged as an independent risk
      factor for carotid atherosclerosis (CA) and cerebrovascular disease in middle
      aged subjects. Currently, there is no study providing a causal relationship
      between SDB and cerebrovascular lesions in elderly. OBJECTIVE: To assess the
      impact of SDB on CA in a cohort of healthy elderly subjects. METHODS: Seven
      hundred and fifty-five participants of a cross-sectional study on the association
      between SDB and cardiovascular morbidity, aged 68yr at study entry, were
      examined. All subjects underwent carotid ultrasonography and risk factors for
      atherosclerosis including smoking, metabolic syndrome and hypertension were
      examined. An apnea + hypopnea index (AHI)>15 was considered indicative of SDB.
      RESULTS: Presence of carotid lesion was found in 35% of the sample, predominantly
      in men and in overweight subjects. The most frequent alteration was
      arteriosclerosis present in 74% of cases, with stenosis >50% found in only 9% of
      subjects. No significant difference in the prevalence of carotid lesion was found
      between subjects with and without SDB, subjects with an AHI>30, even though,
      having a slight increase in CA. At the logistic regression analysis, male gender
      (p<0.001), systolic and diastolic blood pressure (p<0.001), dyslipidemia
      (p=0.003) and hypertension (p=0.009) were the variables independently associated
      with carotid lesions even in severe cases. CONCLUSION: The incidence of CA in
      healthy elderly subjects is mediated more by gender, metabolic factors and
      hypertension than by presence of SDB. Further clinical studies including
      extensive evaluation of all atherosclerotic factors are needed to elucidate the
      predisposing role of SDB for cerebrovascular risk.

PMID- 23127580
TI  - Objective sleep parameters of healthy subjects by actigraphy for the evaluation
      of sleep medication.

PMID- 23127581
TI  - The interaction of Sjogren's syndrome, gastroesophagel reflux and sleep.

PMID- 23127582
TI  - Potential biochemical pathways for the relationship between sleep duration and
      mortality.
AB  - OBJECTIVE: The objective of this study was to elucidate new evidence on the
      presence of a relationship among sleep duration, cardiovascular mortality and
      total mortality, and to investigate sleep duration-related multiple biochemical
      changes. METHODS: The longitudinal study is based on the SAKUCESS study of 12,489
      residents of Japan aged 20-79 years at baseline. RESULTS: In the study, compared
      to respondents who reported 7h of sleep, long sleep duration (>=9h) was
      associated with an increased risk of cardiovascular disease mortality and total
      mortality in men, hazard ratios (HRs) were 1.70 (95% confidence interval
      [CI]=1.07-2.70) and 2.73 (95% CI=1.22-6.11) and an increased risk of total
      mortality in women, HR was 1.85 (95% CI=1.09-3.13). Sleep duration was
      significantly associated with changes in blood biochemical levels. The results of
      the logistic regression analysis showed that the levels of multiple biochemical
      parameters are associated with increased risk of total mortality. CONCLUSIONS:
      This is the first large longitudinal study to indicate that sleep duration was
      associated with changes in multiple biochemical levels in the blood and total
      mortality.

PMID- 23127583
TI  - Restless legs among us.

PMID- 23127584
TI  - Exposure to bright light during evening class hours increases alertness among
      working college students.
AB  - OBJECTIVE: To evaluate the effects of exposure to bright light on sleepiness
      during evening hours among college students. METHODS: Twenty-seven healthy
      college students, all males, with ages ranging from 21 to 24years, working during
      the day and studying in the evening, participated in this study. During the 3week
      study, the students wore actigraphs and recorded levels of sleepiness. In a
      crossover design, on the second and third weeks, the students were exposed to
      bright light (BL) at either 19:00 or 21:00h. Salivary melatonin samples were
      collected before and after BL exposure. ANOVA test for repeated measurements were
      performed. RESULTS: After BL exposure, sleepiness levels were reduced at 20:30
      and 22:00h (F=2.2; p<0.05). ANOVA showed statistical differences between time
      (F=4.84; p=0.04) and between day and time of BL exposure (F=4.24; p=0.05). The
      results showed effects of melatonin onset at 20:00 and 21:30h and sleepiness
      levels (F=7.67; p=0.02) and perception of sleepiness and intervention time
      (F=6.52; p=0.01). CONCLUSION: Controlled exposure to BL during evening hours
      increased alertness among college students. The effects of BL on sleepiness
      varied according to the time of melatonin onset.

PMID- 23127586
TI  - Failing sleep? Beware of frailty or death.

PMID- 23127585
TI  - Experimentally induced arousals do not elicit periodic leg motor activity during
      sleep in normal subjects.
AB  - OBJECTIVE: To evaluate whether eliciting repetitive cortical and autonomic
      arousals during sleep is able to induce the occurrence of periodic leg movements
      during sleep (PLMS). METHODS: Fifteen normal subjects underwent one night of
      uninterrupted and two sequential nights of experimental sleep fragmentation
      achieved by auditory and mechanical stimuli eliciting frequent EEG arousals.
      Sleep was polygraphically recorded and subsequently used to determine the
      frequency of arousals and occurrence of leg movement (LM) activity during the
      first (baseline) and the second fragmentation night. Also, heart rate variability
      parameters were obtained to assess the autonomic changes induced by the
      stimulation. RESULTS: Sleep fragmentation was associated with an increase in the
      arousal index, percentage of sleep stage 1, and frequency of stage shifts. In
      addition, there was a decrease in sleep latency and in percentage of slow-wave
      sleep. Moreover, a significant increase in heart rate variability and especially
      of its sympathetic component, was also found. In contrast, parameters of the leg
      movement activity showed no significant change following experimental sleep
      fragmentation. The lack of an increase in leg movement activity was also observed
      in one subject who demonstrated PLMS at baseline. CONCLUSIONS: Experimental sleep
      fragmentation is not associated with an increase in PLMS in normal young adults.

PMID- 23127587
TI  - Alcohol-mediated sleep paralysis: the earliest known description.

PMID- 23127588
TI  - Low-dose rapamycin unmasks the protective potential of targeting intragraft NF
      kappaB for islet transplants.
AB  - Islet grafts can contribute to their own destruction via the elaboration of
      proinflammatory genes, many of which are transcriptionally regulated by nuclear
      factor kappa-light-chain-enhancer of activated B-cells (NF-kappaB). Thus, NF
      kappaB constitutes an enticing gene therapy candidate to improve the success of
      islet transplantation. To test this hypothesis in vivo, we blocked NF-kappaB in
      BALB/c (H2(d)) to C57/BL6 (H2(b)) mouse islet allografts by genetically
      engineering islets to express the NF-kappaB superrepressor, IkappaBalpha. Here we
      show by microarray and RTqPCR that islets exhibit an intrinsic early immediate
      proinflammatory response, with the most highly upregulated proinflammatory genes
      comprising the chemokines Cxcl1, Cxcl2, Cxcl10, and Ccl2; the cytokines Tnf-alpha
      and Il-6; and the adhesion molecule Icam1. Overexpression of IkappaBalpha
      inhibited the expression of these genes by 50-95% in islets and MIN6 beta-cells
      in vitro, by inhibiting NF-kappaB-dependent gene transcription. Histological and
      RTqPCR analysis at postoperative day (POD) 10 revealed that IkappaBalpha
      transduced islet allografts exhibited improved islet architecture and strong
      insulin-labeling with decreased Ccl2 and Il-6 mRNA levels compared to the GFP
      transduced control grafts. Despite these protective effects, NF-kappaB-blocked
      islet allografts were promptly rejected in our MHC-mismatched mouse model.
      However, IkappaBalpha-expressing grafts did harbor localized "pockets" of
      Foxp3(+) mononuclear cells not evident in the control grafts. This result
      suggested that the effect of the NF-kappaB blockade might synergize with
      regulatory T-cell-sparing rapamycin. Indeed, combining intragraft IkappaBalpha
      expression with low-dose rapamycin increased the mean survival time of islet
      allografts from 20 to 81 days, with 20% of the grafts surviving for greater than
      100 days. In conclusion, rapamycin unmasks the protective potential of intragraft
      NF-kappaB blockade, which can, in some cases, permit permanent allograft survival
      without continuous systemic immunosuppression. 

PMID- 23127589
TI  - Access to dental services for head and neck cancer patients.
AB  - Dental assessment is important for patients with cancer of the head and neck who
      are to have radiotherapy, as many of these patients have poor dental health
      before they start treatment. This, compounded by the fact that radiotherapy to
      the head and neck has a detrimental effect on oral health, has led the National
      Institute for Clinical Excellence (NICE) to issue guidance that the dental health
      of these patients should be assessed before treatment. Unfortunately some
      multidisciplinary teams, such as the one at United Lincolnshire Hospitals, do not
      have access to a restorative dentist or a dental hygienist. In a retrospective
      survey we investigated access to general dental services by patients with head
      and neck cancer who were to have radiotherapy at our hospital and found that
      37/71 (52%) had not been reviewed by a dentist within the past 12 months. A
      secondary national survey that investigated the availability of restorative
      dental and dental hygienic services showed that of the 56 multidisciplinary teams
      that deal with head and neck cancer in England, 19 (34%) do not have access to a
      restorative dentist and 23 (41%) do not have access to a dental hygienist,
      suggesting that this problem may be countrywide.

PMID- 23127590
TI  - Morphologic abnormalities in 2-year-old children born after in vitro
      fertilization/intracytoplasmic sperm injection with preimplantation genetic
      screening: follow-up of a randomized controlled trial.
AB  - OBJECTIVE: To evaluate the effect of preimplantation genetic screening (PGS) on
      morphologic outcome in children. DESIGN: Follow-up of a randomized controlled
      trial (RCT). SETTING: University hospital. PATIENT(S): Two-year-old children born
      to mothers who participated in an RCT on the efficacy of PGS: 50 children born
      after in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) with
      PGS (intervention group; PGS+) and 72 children born after IVF/ICSI only (control
      group; PGS-). Sixty-six age-matched children conceived without any form of
      assisted reproduction were recruited separately in a local public health service
      center (reference group). INTERVENTION(S): PGS. MAIN OUTCOME MEASURE(S): Body
      surface examination and anthropometry. The evaluation of morphologic
      abnormalities allowed assessment of children's phenotype in detail. Morphologic
      abnormalities were classified as major abnormalities (abnormal development in
      organogenesis, deformations, disruptions, or dysplasia) and minor anomalies
      (deviations in phenogenesis). RESULT(S): The percentage of children with >= 1
      major abnormality was 28% in the PGS+ and 35% in the PGS- group [difference -7%,
      95% CI -23% to 10%]. The percentage of children with >= 1 minor anomaly was 64%
      in the PGS+ and 67% in the PGS- group [difference -3%, 95% CI -15% to 20%]. In
      the reference group 30% of the children had >= 1 major abnormality [95% CI 20% to
      43%] and 74% had >= 1 minor anomaly [95% CI 62% to 84%]. CONCLUSION(S): No
      statistically significant differences were found in minor anomalies between
      children conceived after IVF/ICSI with or without PGS. There is < 2.5% chance of
      >= 10% more major abnormalities in children born after PGS.

PMID- 23127591
TI  - Effective anatomical and functional status of the lower uterine segment at term:
      estimating the risk of uterine dehiscence by ultrasound.
AB  - OBJECTIVE: To define the role of lower uterine segment (LUS) evaluation at term.
      DESIGN: Observational case-control study. SETTING: University hospital.
      PATIENT(S): Ninety-four patients were divided into two groups. Group A consisted
      of 45 multiparous single fetus pregnant women with up to two previous cesarean
      sections (CS). Group B consisted of 49 multiparous pregnant women with up to
      three vaginal deliveries and no uterine scars. INTERVENTION(S): Total LUS and
      myometrial thickness were measured by sonogram in all patients before undergoing
      a CS. MAIN OUTCOME MEASURE(S): The primary outcome is a correlation between
      echographic measurements and features of the LUS at the time of CS. The secondary
      outcome is a definition of a correlation between the number of previous CS,
      interdelivery interval time, and features of the LUS (grades I-IV). RESULT(S):
      Sonographic measurements revealed significant differences in LUS size and
      myometrial thickness between the two groups. Grades III and IV of LUS were only
      observed in group A. An interdelivery interval <18 months, LUS thickness <= 3.0
      mm, and myometrial thickness < 1.5 mm were statistically significant predictors
      of LUS grades III and IV. Number of previous CS showed no correlation with
      surgical LUS status. CONCLUSION(S): Sonographic evaluation of the LUS may be a
      noninvasive, reproducible, and safe technique for defining the risk of uterine
      dehiscence, with a sensitivity of 100% and specificity of 85% (positive
      predictive value, 45%; negative predictive value, 100%).

PMID- 23127592
TI  - Relationships between serum uric acid, adiponectin and arterial stiffness in
      postmenopausal women.
AB  - OBJECTIVES: Cardiovascular disease (CVD) is a leading cause of death in
      postmenopausal women. Elevated serum uric acid levels, hypoadiponectinemia and
      arterial stiffness are strongly associated with cardiovascular diseases. We
      investigated the relationships among uric acid, adiponectin and arterial
      stiffness in postmenopausal women. STUDY DESIGN: 9555 subjects who had the
      routine health check-ups, 841 postmenopausal women aged 50 years or older who had
      not had a menstrual period for more than 12 consecutive months were included in
      this study. MAIN OUTCOME MEASURES: BMI, WC, and serum concentrations of uric
      acid, adiponectin, glucose, lipids (total cholesterol, triglycerides, LDL
      cholesterol, and HDL cholesterol) were measured. Insulin resistance was estimated
      by the insulin resistance index of homeostasis model assessment (HOMA-IR). Pulse
      wave velocity (PWV) was evaluated to assess arterial stiffness. RESULTS: The
      subjects were stratified into three groups according to uric acid values. PWV
      values gradually increased and adiponectin level decreased with uric acid
      tertiles. Serum uric acid levels in postmenopausal women correlated significantly
      with age, BMI, WC, TG, HDL-C, insulin, HOMA-IR, adiponectin and PWV. Multiple
      regression analysis showed that WC (beta=0.141, P<0.01), HOMA (beta=0.137,
      P<0.01), adiponectin (beta=-0.104, P<0.01), and PWV (beta=0.129, P<0.01) were
      independently correlated with uric acid levels. In multiple logistic regression
      analysis after adjusting for risk factors, uric acid was a significant
      contributor to increased PWV. CONCLUSIONS: These findings indicate that serum
      uric acid is independently associated with adiponectin and arterial stiffness in
      postmenopausal women.

PMID- 23127593
TI  - Reliability of self-report on basic health conditions in Mexican Americans Age 80
      and older.
AB  - Reliability of self-reports in survey research is important. Little is known
      about the reliability of self-reports in the very old (aged 80+). The objective
      of this study is to evaluate the level of reliability in self-reports by
      assessing the level of agreement between a "respondents" and their "informants"
      (children) as they rate the respondent's: hearing ability; vision capacity; and
      nine health conditions. Descriptive statistics, observed agreement, and kappa
      values are computed on 389 pairs using HEPESE Wave-7 data (2010-2011). Although
      further studies are required, there is evidence that self-reports on basic health
      conditions in the very old are reliable.

PMID- 23127594
TI  - Molecular analysis of the TGF-beta controlled gene expression program in chicken
      embryo dermal myofibroblasts.
AB  - The myofibroblast is a mesenchymal cell characterized by synthesis of the
      extracellular matrix, plus contractile and secretory activities. Myofibroblasts
      participate in physiological tissue repair, but can also cause devastating
      fibrosis. They are present in the tumor stroma of carcinomas and contribute to
      tumor growth and spreading. As myofibroblasts derive from various cell types and
      appear in a variety of tissues, there is marked variability in their phenotype.
      As regulatory mechanisms of wound healing are likely conserved among vertebrates,
      detailed knowledge of these mechanisms in more distant species will help to
      distinguish general from specific phenomena. To provide this as yet missing
      comparison, we analyzed the impact of the chemical inhibition of TGF-beta
      signaling on gene expression in chicken embryo dermal myofibroblasts. We revealed
      genes previously reported in mammalian systems (e.g. SPON2, ASPN, COMP, LUM,
      HAS2, IL6, CXCL12, VEGFA) as well as novel TGF-beta dependent genes, among them
      PGF, VEGFC, PTN, FAM180A, FIBIN, ZIC1, ADCY2, RET, HHIP and DNER. Inhibition of
      TGF-beta signaling also induced multiple genes, including NPR3, AGTR2, MTUS1,
      SOD3 and NOV. We also analyzed the effects of long term inhibition, and found
      that it is not able to induce myofibroblast dedifferentiation.

PMID- 23127595
TI  - Host RNA polymerase inhibitors encoded by phiKMV-like phages of Pseudomonas.
AB  - Escherichia coli bacteriophage T7 is a founding member of a large clade of
      podoviruses encoding a single-subunit RNA polymerase (RNAP). Phages of the family
      rely on host RNAP for transcription of early viral genes; viral RNAP transcribes
      non-early viral genes. T7 and its close relatives encode an inhibitor of host
      RNAP, the gp2 protein. Gp2 is essential for phage development and ensures that
      host RNAP does not interfere with viral RNAP transcription at late stages of
      infection. Here, we identify host RNAP inhibitors encoded by a subset of T7 clade
      phages related to phiKMV phage of Pseudomonas aeruginosa. We demonstrate that
      these proteins are functionally identical to T7 gp2 in vivo and in vitro. The
      ability of some Pseudomonas phage gp2-like proteins to inhibit RNAP is modulated
      by N-terminal domains, which are absent from the T7 phage homolog. This finding
      indicates that Pseudomonas phages may use external or internal cues to initiate
      inhibition of host RNAP transcription and that gp2-like proteins from these
      phages may be receptors of these cues.

PMID- 23127596
TI  - Isolation and genomic characterization of Chaoyang virus strain ROK144 from Aedes
      vexans nipponii from the Republic of Korea.
AB  - During June 2003, mosquito surveillance was conducted at a US Army installation
      and a US Military training site 2 km south of the demilitarized zone, Republic of
      Korea. Mosquitoes were collected using Mosquito MagnetsTM, sorted to species, and
      assayed for the presence of arboviruses. From the 3,149 mosquitoes that were
      sorted into 126 pools, one Aedes vexans nipponii pool (out of 73 pools) tested
      positive for flavivirus RNA by reverse transcription-PCR. After isolation from
      C6/36 cell culture supernatant, the viral genome was sequenced and found to be
      98.9% related to Chaoyang virus, a potential arthropod-specific flavivirus. This
      report details the first identification of Chaoyang virus in the Republic of
      Korea and highlights its relationship to other flaviviruses.

PMID- 23127597
TI  - Acrylamide-induced mitochondria collapse and apoptosis in human astrocytoma
      cells.
AB  - Acrylamide (ACR) can be produced during food processing and has neurotoxic
      effects in humans. This study aims to determine ACR induced apoptotic responses
      in human astrocytoma U-1240 MG cells to realize the incurred toxic mechanisms.
      Under 1 and 2mM ACR exposure, cell viability decreased as time increased. The
      increments in sub-G(1) phase were 87.5-fold, and pro-caspase 3 and PARP protein
      expressions decreased 35% and 54.5% respectively relative to the control after
      2mM ACR treatment. Molecular evidence of Bax/bcl-2 ratio and cytochrome c
      expression increased 8.86-fold and 6.81-fold as well as pro-caspase 9 decreased
      67.8% relative to the control respectively under 2mM ACR exposure. Trolox, an ROS
      scavenging agent, attenuated cell death and induced ROS production by 2mM ACR.
      The ultrastructure alterations of mitochondria showed marked vesicular matrix
      compartmentalization and cytoplasmic vacuole formation after 2mM ACR was treated
      for 48h, whereas those treated for 72h showed chromatin condensation, pyknosis,
      and swelling. These results indicate long-term exposure to ACR induced
      mitochondria collapse and finally led to apoptosis. Although 2mM ACR is higher
      than average daily intake dosage, workers in chemical industries may be exposed
      to sufficient doses to entail health risks.

PMID- 23127598
TI  - Absorption of triphenylmethane dyes Brilliant Blue and Patent Blue through intact
      skin, shaven skin and lingual mucosa from daily life products.
AB  - Currently, there is evidence of health risks of triphenylmethane dyes after
      systemic absorption. This paper investigates the fate of Brilliant Blue (BB) and
      Patent Blue (PB) after 24-h in vitro diffusion, firstly through intact and
      secondly through shaven pig-ear skin (stored by freezing) from four leave-on
      cosmetics under in-use conditions. Both dyes showed no measurable permeation
      through intact skin but significant permeation was found through shaven skin.
      From 250 ng/cm(2) of dye in one applied dose there were found 52 ng/cm(2) of BB
      and 91 ng/cm(2) of PB from ethanol-based after-shave, 39 ng/cm(2) of BB and 86
      ng/cm(2) of PB from ethanol-free facial-cleanser, 35 ng/cm(2) of BB and 43
      ng/cm(2) of PB from O/W emulsion, and no amount from W/O emulsion, as available
      to become systemically absorbed. Thirdly, the paper focuses on lingual mucosa
      after licking lollipops. Ex vivo porcine tongue dorsum was exposed to human
      saliva with 15,000 ng/cm(2) of dye for 20 min. 24-h diffusion resulted in 34
      ng/cm(2) of BB and 86 ng/cm(2) of PB which can be directly absorbed into the
      blood system. Findings are troubling, particularly with regard to the frequent
      use of after-shave products by the male population and repeated lollipops licking
      by children.

PMID- 23127599
TI  - Alleviative effects of resveratrol on nonalcoholic fatty liver disease are
      associated with up regulation of hepatic low density lipoprotein receptor and
      scavenger receptor class B type I gene expressions in rats.
AB  - Lipid metabolic disorders are widely considered to be one of the most critical
      and basic link in the pathogenesis of nonalcoholic fatty liver disease (NAFLD).
      The aim of this study was to illustrate the alleviation function of resveratrol
      (Res) on NAFLD and the roles of hepatic fatty acid synthase (FAS), low density
      lipoprotein receptor (LDLr), scavenger receptor class B type I (SR-BI), and
      thyroid hormone receptor beta1 (TRbeta1), which are the key molecules involved in
      lipid metabolism. Adult male Wistar rats were fed a normal diet or high
      fat/sucrose diet (HFS) with or without resveratrol for 13 weeks. HFS induced
      NAFLD formation and increased the lipids concentrations in serum and livers of
      rats, while noticeable improvement has been reached by Res intervention.
      Moreover, Res protected against HFS-induced decrease in hepatic LDLr and SR-BI
      mRNA and protein expressions, whereas TRbeta1 expressions were impervious
      with/without Res. Unexpectedly, hepatic FAS gene expressions were markedly
      diminished in NAFLD rats and were gradually increased by treatment with Res.
      These data indicate that the alleviative effects of Res on NAFLD are associated
      with up regulation of hepatic LDLr and SR-BI gene expressions, which provide new
      insights into the pharmacological targets of Res in the prevention of NAFLD.

PMID- 23127600
TI  - Protective effect of cinnamon polyphenols against STZ-diabetic mice fed high
      sugar, high-fat diet and its underlying mechanism.
AB  - This study was designed to investigate the potential effects of 14days'
      intragastrically given of cinnamon polyphenols (CPS) in treating diabetic mice
      induced by intraperitoneal injection of streptozotocin (150mgkg(-1)) and fed high
      sugar, high-fat diet. The diabetic mice model was successfully established
      through determining on fasting blood-glucose (FBG) test. As revealed by glucose
      oxidase (GOD) and radioimmunoassay (RIA), both dimethyldiguanide (DC, 0.6gkg(
      1)d(-1)) and CPS (0.3, 0.6, 1.2gkg(-1)d(-1)) treatments significantly resulted in
      down-regulation of blood glucose and insulin levels in serum, while the levels of
      oxidative stress markers were markedly lowered through ELISA assay. Meanwhile,
      the pathological damage in islet with pancreatic beta cells was ameliorated by
      treatment of CPS at different doses, as shown in HE stain. At the same time, the
      treatments also caused notable reduction of iNOS, NF-kappaB expressions showing
      in Western blot analysis. These findings demonstrate that cinnamon polyphenols
      can exert the hypoglycemic and hypolipidemic effects through the mechanisms that
      may be associated with repairing pancreatic beta cells in diabetic mice and
      improving its anti-oxidative capacity, as well as attenuating cytotoxicity via
      inhibition of iNOS, NF-kappaB activation.

PMID- 23127601
TI  - Consumption of tomato products is associated with lower blood mercury levels in
      Inuit preschool children.
AB  - Some evidence suggests that various diet components and nutrients, including
      vegetables, fruit and food-derived antioxidants, could mitigate contaminant
      exposure and/or adverse health effects of contaminants. To examine the effect of
      the consumption of tomato products on blood mercury levels in Inuit preschool
      children, 155 Inuit children (25.0+/-9.1months) were recruited from 2006-2008 in
      Nunavik childcare centers (northern Quebec, Canada). Food frequency
      questionnaires were completed at home and at the childcare center, and total
      blood mercury concentration was measured by inductively coupled plasma-mass
      spectrometry. Multivariate regression analysis was performed after multiple
      imputation. The median blood concentration of mercury was 9.5nmol/L. Age,
      duration of breastfeeding, annual consumption frequency of seal meat, and monthly
      consumption frequency of tomato products were significant predictors of blood
      mercury levels, whereas annual consumption frequencies of beluga muktuk, walrus,
      Arctic char, and caribou meat were not. Each time a participant consumed tomato
      products during the month before the interview was associated with a 4.6% lower
      blood mercury level (p=0.0005). All other significant predictors in the model
      were positively associated with blood mercury levels. Further studies should
      explore interactions between consumption of healthy store-bought foods available
      in Arctic regions and contaminant exposure.

PMID- 23127602
TI  - Distribution, fate and histopathological effects of ethion insecticide on
      selected organs of the crayfish, Procambarus clarkii.
AB  - This study aims to investigate the fate and histopathological effects of ethion
      on selected organs of the crayfish, Procamabrus clarkii. Crayfish were exposed to
      1 mg l(-1) (14)C-ethion and the concentrations of ethion and its possible
      degradation products were measured in water and different organs of the crayfish
      over both the exposure and recovery periods. Chromatographic analysis revealed
      that ethion was degraded into ethion monooxon, ethion dioxon, O,O-diethyl
      phosphorothioate, O-ethyl phosphorothioate and one unknown compound. At the end
      of exposure period, ethion was accumulated in different organs of the crayfish
      especially in the hepatopancreas and gills. Following the transfer of crayfish to
      clean water for seven days, the concentration of insecticide residues were
      decreased in both the hepatopancreas and gills suggesting that these organs play
      an important role in elimination of ethion. On the other hand, the exposure of
      the crayfish to 1/4 96 h-LC(50) (0.36 mg l(-1)) of ethion caused extensive
      ultrastructural alterations to both hepatopancreas and gill epithelial cells. In
      the hepatopancreas, the most notable pathological features included vacuolation,
      degradation and distinct cell lysis. In the gill epithelium, the
      histopathological alterations included infiltration of hemocytes, cytoplasmic
      vacuolation and a decrease in the number of basal plasma membrane infoldings.

PMID- 23127603
TI  - Japanese database of families with twins and higher-order multiples.
AB  - To gain widespread participation, epidemiologic studies of twins from pregnancy
      through the childhood period are expected to reflect the needs and concerns of
      families and provide participants with appropriate and useful feedback based on
      scientific evidence. Our most recent database on families with twins throughout
      Japan is based on a questionnaire survey conducted from January 2010 to August
      2011. Mailed or hand-delivered questionnaires, consisting of over 550 items were
      used to collect the basic data. The response rate was 40% (956/2,401). This is
      part of a nation-wide study designed to assess the long-term effect of perinatal
      conditions on mothers of multiples. Its aim was to study the growth and
      development of multiples in childhood, and to conduct a genetic epidemiologic
      study to test the developmental origin of health and disease hypothesis. One of
      the ultimate aims of this research was to provide evidence-based information on
      parenting multiples from pregnancy through childhood to families with multiples.

PMID- 23127604
TI  - Differences in sexual desire between women with clinical versus biochemical signs
      of hyperandrogenism in polycystic ovarian syndrome.
AB  - The role androgens play in female sexual desire remains unclear. We investigated
      whether androgen sensitivity or elevated androgen levels contributed to sexual
      desire using a motivational model of sexual desire. Eighty-five women diagnosed
      with polycystic ovary syndrome (PCOS) were categorized depending on whether they
      exhibited clinical symptoms of androgen sensitivity or high biochemical androgen
      levels. Additionally, instead of looking at desire as a uniform construct, we
      divided desire based on the reasons why women experienced desire, thus
      distinguishing desire to have sex for relational purposes from the desire to have
      sex for mating selection or physical pleasure. Findings confirmed that clinical
      signs suggesting sensitivity to androgen levels, but not biological levels of
      androgens per se predicted levels of sexual desire. Moreover, in agreement with
      our hypothesis, we found support for a relationship between androgen sensitivity
      and some, but not other aspects of sexual desire. Cues that are most closely
      related to mating selection were significantly associated with androgen
      sensitivity, but not cues associated with desiring sex to feel emotionally close
      or create a love bonding with a partner. This study presents a new way to
      investigate desire and shows some preliminary findings on the importance to
      consider androgen sensitivity when investigating the relationship between sexual
      desire and hormones.

PMID- 23127605
TI  - Evaluation of curriculum to improve health professionals' ability to manage age
      related driving impairments.
AB  - As our elderly population increases in proportion with respect to the rest of
      society, age-related driving impairments are increasing in importance as a public
      health concern. In this context, health professionals play an important role in
      identifying impaired drivers. This situation is complicated for two reasons:
      discussion of driving cessation is a sensitive topic for both health
      professionals and the elderly, and physicians have limited familiarity with the
      current American Medical Association (AMA) screening guidelines or mandated
      reporting laws. To assess curriculum that trains health professionals to increase
      their awareness, screening, management, and reporting of age-related driving
      impairments. Between 2009 and September 2011, 47 trainings were delivered to 1202
      health professionals. The majority of trainings were seminars or lectures lasting
      1h; all were conducted in southern California. The training curriculum was
      divided into four sections: introduction and background; screening and
      interpretation; managing outcomes and reporting; and referrals and resources.
      Videos addressed broaching the topic with patients and counseling on driving
      cessation. The curriculum was delivered by physicians with the support of public
      health-trained program staff. Pre- and post-testing was done with 641 of the
      participants; the majority were physicians. Post-training, participants'
      confidence in ability to screen increased to 72% and intent to screen increased
      to 55%. Fully 92% stated they had developed a better understanding of
      California's mandated reporting laws. Similarly, 92% said they had developed a
      better understanding of the medical conditions and medications that may impair
      older adults' ability to drive safely. Furthermore, 91% said mandated-reporting
      laws helped protect the safety of patients and others, and 59% said it was easier
      to discuss and justify driving cessation with patients. In-person training of
      health professionals on age-related driving impairments was well received and
      resulted in increased self-reported knowledge, confidence to screen, and intent
      to screen. Physicians were supportive of mandatory reporting laws. 

PMID- 23127606
TI  - Ultrastructure and molecular phylogeny of the cryptomonad Goniomonas avonlea sp.
      nov.
AB  - We describe a new species of cryptomonad, Goniomonas avonlea sp. nov., using
      molecular phylogeny and comprehensive microscopic investigation. G. avonlea is a
      marine bacterivorous flagellate, measuring 8-11 MUm long and 6-7 MUm wide, with
      two subequal flagella that are directed anteriorly and posteriorly. G. avonlea is
      morphologically and genetically distinct from three other Goniomonas species that
      have been described to date. SEM and TEM show that G. avonlea shares
      ultrastructural features with other Goniomonas and cryptomonads, including the
      presence of bipartite ejectisomes, double septa in the transition region, flat
      mitochondrial cristae, a furrow complex, a rhizostyle, rectangular periplast
      plates, and the infundibulum. The discharged large ejectisome is straight and has
      a unique loose, reticulate layer. The flagellar apparatus includes non-tubular
      roots, microtubular roots, and a compound root that is reminiscent of the
      multilayered structure (MLS) observed in the flagellate cells of streptophytes
      and a few other eukaryotes. Molecular phylogenies based on 18S and 28S rRNA genes
      suggest a specific affiliation of G. avonlea to marine Goniomonas species, and
      support the monophyly of Goniomonas to the exclusion of plastid-bearing
      cryptomonads. Our study adds to a growing body of evidence for the high level of
      diversity and antiquity of the genus Goniomonas.

PMID- 23127607
TI  - Consequences of telomere shortening during lifespan.
AB  - Telomerase expression is restricted in human cells and so telomeres shorten
      throughout our lives, providing a tumour suppressor mechanism that limits cell
      proliferation. As a trade-off, continuous telomere erosion results in replicative
      senescence and contributes to ageing. Recently, telomerase therapies were
      proposed as a valid approach to rescue degenerative phenotypes caused by telomere
      dysfunction. However, systemic effects initiated by short telomeres may prove
      dominant in limiting tissue renewal in the whole organism. Most of our knowledge
      of telomere biology derives from mouse models that do not rely on telomere
      exhaustion for controlling cell proliferation and tissue homeostasis. In order to
      understand the impact of telomere shortening in natural ageing, we need to
      investigate animal models that, like humans, have evolved to have telomere length
      as a cell division clock.

PMID- 23127608
TI  - Cadherin junctions and their cytoskeleton(s).
AB  - Classical cadherin adhesion receptors exert many of their biological effects
      through close cooperation with the cytoskeleton. Much attention has focused on
      attempting to understand the physical interactions between cadherin molecular
      complexes and cortical actin filaments. In this review we aim to draw attention
      to other issues that highlight the diverse and dynamic cytoskeletons that
      contribute to cadherin function. First, we discuss the regulation of actin
      filament dynamics in the cadherin-based junctional cytoskeleton, focusing on the
      emerging role of Arp2/3 as a junctional actin nucleator and its implications for
      actin homeostasis at junctions. Second, we review recent developments in
      understanding the impact of microtubules on cadherin function. Together, these
      emphasize that cadherins cooperate with multiple dynamic cytoskeletal networks at
      cell-cell junctions.

PMID- 23127610
TI  - Fission yeast: in shape to divide.
AB  - How are cell morphogenesis and cell cycle coordinated? The fission yeast is a rod
      shaped unicellular organism widely used to study how a cell self-organizes in
      space and time. Here, we discuss recent advances in understanding how the cell
      acquires and maintains its regular rod shape and uses it to control cell
      division. The cellular body plan is established by microtubules, which mark
      antipodal growth zones and medial division. In turn, cellular dimensions are
      defined by the small GTPase Cdc42 and downstream regulators of vesicle
      trafficking. Yeast cells then repetitively use their simple rod shape to
      orchestrate the position and timing of cell division.

PMID- 23127609
TI  - Centrosomes, chromosome instability (CIN) and aneuploidy.
AB  - Each time a cell divides its chromosome content must be equally segregated into
      the two daughter cells. This critical process is mediated by a complex
      microtubule based apparatus, the mitotic spindle. In most animal cells the
      centrosomes contribute to the formation and the proper function of the mitotic
      spindle by anchoring and nucleating microtubules and by establishing its
      functional bipolar organization. Aberrant expression of proteins involved in
      centrosome biogenesis can drive centrosome dysfunction or abnormal centrosome
      number, leading ultimately to improper mitotic spindle formation and chromosome
      missegregation. Here we review recent work focusing on the importance of the
      centrosome for mitotic spindle formation and the relation between the centrosome
      status and the mechanisms controlling faithful chromosome inheritance.

PMID- 23127611
TI  - Sequencing of t(2;7) translocations reveals a consistent breakpoint linking CDK6
      to the IGK locus in indolent B-cell neoplasia.
AB  - The translocation t(2;7)(p11;q21) has repeatedly been documented in association
      with indolent B-cell lymphoproliferative disorders (BLPDs). However, the
      chromosomal breakpoints associated with this recurrent translocation have rarely
      been characterized. Using an approach based on long-range PCR, we mapped the
      t(2;7) breakpoints in five patients presenting with indolent B-cell neoplasia.
      The sequencing of these rearrangements revealed several striking parallels across
      the t(2;7) breakpoints. The junction sites on 2p11 consistently mapped to the
      heptamer recombination signal sequence (RSS) of an immunoglobulin kappa variable
      gene (IGK) within the Vkappa3 family, while the breakpoints on 7q21 each
      localized to within 4 bp of an RSS-like element located approximately 0.5 kb
      upstream of the transcription start site of the cyclin-dependent kinase 6 gene
      (CDK6). These findings confirm the significant genetic overlap arising in BLPD
      associated t(2;7) translocations, and implicate the deregulated expression of
      CDK6 as a common molecular mechanism involved in the emergence of clonal B-cell
      proliferations presenting with this recurrent abnormality. In addition, the
      successful mapping of the t(2;7) translocations in each of five patients using a
      simple PCR-based protocol highlights the potential diagnostic utility of this
      approach during characterization of cases harboring analogous rearrangements.

PMID- 23127612
TI  - Conventional and nanotechniques for DNA methylation profiling.
AB  - DNA methylation is critical for gene silencing and is associated with the
      incidence of many diseases, including cancer. Underlying molecular mechanisms of
      human diseases and tissue-specific gene expression have been elucidated based on
      DNA methylation studies. This review highlights the advantages and drawbacks of
      various methylation screening techniques: blotting, genomic sequencing, bisulfite
      sequencing, methylation-specific PCR, methylated DNA immunoprecipitation,
      microarray analysis, matrix-assisted laser desorption ionization time-of-flight
      mass spectroscopy, nanowire transistor detection procedure, quantum dot-based
      nanoassay, single-molecule real-time detection, fluorimetric assay,
      electrochemical detection, and atomic force spectroscopy. The review provides
      insight for selecting a method or a combination of methods for DNA methylation
      analysis. Convergence of conventional and contemporary nanotechniques to
      enumerate methylation at specific CpG sites of oncogene would fill the gap in
      diagnosis of cancer.

PMID- 23127613
TI  - Anaemia predicts health related quality of life in heart failure patients.

PMID- 23127614
TI  - beta-blocker use in patients after percutaneous coronary interventions: one size
      fits all? Worse outcomes in patients without myocardial infarction or heart
      failure.
AB  - BACKGROUND: The influence of beta-blocker therapy on prognosis in patients with
      coronary artery disease (CAD) who underwent percutaneous coronary intervention
      (PCI) has not been fully explored. METHODS AND RESULTS: We identified 5288 CAD
      patients who did not have myocardial infarction (MI) or heart failure (HF) but
      underwent PCI from a large multi-center registry enrolling consecutive patients
      undergoing first coronary revascularization from 2005 to 2007. The primary
      outcome was a composite endpoint of cardiac death and/or MI (cardiac death/MI) at
      3 years after hospital discharge for PCI. beta-blockers were prescribed in 1117
      patients (beta group, 21.1%) at discharge, while 4171 patients did not (no-beta
      group, 78.9%). Patients in the beta group more often had hypertension,
      multivessel disease, use of statin and angiotensin-converting enzyme
      inhibitors/angiotensin receptor blockers, but less often had chronic obstructive
      pulmonary disease. The 3-year incidence of cardiac death/MI was higher in the
      beta group (4.9% vs. 3.4%, log-rank p=0.02). After adjusting for potential
      confounders, beta-blocker therapy was associated with significantly increased
      risk for cardiac death/MI (hazard ratio 1.48, 95% confidence interval 1.05-2.10,
      p=0.02). CONCLUSIONS: beta-blocker therapy was associated with worse 3-year
      clinical outcomes in CAD patients who underwent PCI but had no history of MI or
      HF. Randomized trials are warranted to identify appropriate subsets of patients
      who could truly benefit from long-term use of beta-blockers in this setting.

PMID- 23127615
TI  - The scholarship of teaching as science and as art.

PMID- 23127616
TI  - Integrating psychosocial care into medical-surgical nursing.

PMID- 23127617
TI  - Parkinson's disease: from genetics to treatments.
AB  - Parkinson's disease (PD) is a common neurodegenerative disease and typically
      presents with tremor, rigidity, bradykinesia, and postural instability. The
      hallmark pathological features of PD are loss of dopaminergic neurons in the
      substantia nigra (SN) and the presence of neuronal intracellular Lewy body (LB)
      inclusions. In general, PD is sporadic; however, familial PD, while uncommon, can
      be inherited in an autosomal dominant (AD) or autosomal recessive (AR) manner.
      The molecular investigations of proteins encoded by PD-linked genes have
      clarified that ADPD is associated with alpha-synuclein and LRRK2, while ARPD is
      linked to Parkin, PINK1, DJ1, and ATP13A2. Understanding these genes can bring
      insights into this disease and create possible genetic tests for early diagnosis.
      Long-term pharmacological treatment is so far disappointing, probably due to
      unwanted complications and decreasing drug efficacy. Several strategies have been
      proposed and tested as alternatives for PD. Cellular transplantation of dopamine
      secreting stem cells opens the door to new therapeutic avenues for restoration of
      the functions of degenerative and/or damaged neurons in PD. 

PMID- 23127618
TI  - Medication dosing in critically ill patients with acute kidney injury treated
      with renal replacement therapy.
AB  - Critically ill patients with acute kidney injury may be treated with a variety of
      renal replacement therapies (RRTs). Each of these RRTs has profound yet differing
      effects on drug dosing. Although the doses of some drugs can be titrated to an
      immediately observable pharmacodynamic effect, the effects of many drugs, such as
      antibiotics for example, are not immediately apparent. Attainment of desired
      pharmacodynamic response is a complex interplay between patient, RRT, and
      pharmacokinetic factors. In the case of antibiotics, microorganism-specific
      factors also must be considered. Rational and effective drug dosing in this
      clinical setting cannot occur until all these issues are addressed by the
      clinician. Failure to account for the pharmacokinetic influences of critical
      illness, kidney disease, and choice of intermittent hemodialysis or prolonged
      intermittent or continuous RRT can contribute to the high mortality rates seen in
      these patients. Pharmacotherapy considerations for each of these therapies are
      addressed in this article by applying them to a patient case.

PMID- 23127619
TI  - The DOPPS Practice Monitor for US dialysis care: trends through December 2011.

PMID- 23127620
TI  - Terminal sliding mode tracking control for a class of SISO uncertain nonlinear
      systems.
AB  - In this paper, the terminal sliding mode tracking control is proposed for the
      uncertain single-input and single-output (SISO) nonlinear system with unknown
      external disturbance. For the unmeasured disturbance of nonlinear systems,
      terminal sliding mode disturbance observer is presented. The developed
      disturbance observer can guarantee the disturbance approximation error to
      converge to zero in the finite time. Based on the output of designed disturbance
      observer, the terminal sliding mode tracking control is presented for uncertain
      SISO nonlinear systems. Subsequently, terminal sliding mode tracking control is
      developed using disturbance observer technique for the uncertain SISO nonlinear
      system with control singularity and unknown non-symmetric input saturation. The
      effects of the control singularity and unknown input saturation are combined with
      the external disturbance which is approximated using the disturbance observer.
      Under the proposed terminal sliding mode tracking control techniques, the finite
      time convergence of all closed-loop signals are guaranteed via Lyapunov analysis.
      Numerical simulation results are given to illustrate the effectiveness of the
      proposed terminal sliding mode tracking control.

PMID- 23127621
TI  - Capturing hormones and bisphenol A from water via sustained hydrogen bond driven
      sorption in polyamide microfiltration membranes.
AB  - This work investigates the distinct sorption properties of polyamide 66 (PA)
      microfiltration membranes for estrogenic compounds in water. Four representative
      estrogenic endocrine disruptors, namely estrone (E1), 17beta-estradiol (E2),
      17alpha-ethynylestradiol (EE2) and bisphenol A (BPA), were readily captured from
      water via sustained sorption in PA microfiltration membranes during crossflow
      filtration. Such significant sorption was only observed on PA membranes among
      seven polymeric membrane materials tested, including polyethersulfone (PES),
      cellulose acetate (CA), mixed nitrocellulose (MCE), polyester (PETE), regenerated
      cellulose (RC), polycarbonate (PC), and PA. The strong binding affinity
      originates from the hydrogen bonding interactions between PA amide groups and the
      proton-donating moieties of the target compound molecules. For hormone compounds,
      a correlation was further identified between their proton-donating moieties and
      sorption capacities in PA membranes. Using 0.2 MUM (46-59 MUg L(-1)) compound
      spiked solutions, the 0.2-MUm PA membrane exhibited a sorption capacity of 81 L
      m(-2) (0.44 MUg cm(-2)) for E1, 150 L m(-2) (0.82 MUg cm(-2)) for E2, 208 L m(-2)
      (1.23 MUg cm(-2)) for EE2, and 69 L m(-2) (0.32 MUg cm(-2)) for BPA. The sorption
      capacity of PA membrane was largely unaffected by membrane flux or the co
      presence of multiple target compounds or humic acid, but showed strong dependence
      on the membrane surface area and the compound concentration. The hydrogen bond
      driven sorption is a reversible process and desorption was effected by contacting
      exhausted PA membranes with 0.4 wt.% caustic solution at room temperature. The PA
      membrane exhibited consistent sorption capacities for the four target compounds
      in water through three cycles of reuse.

PMID- 23127622
TI  - Colloid retention mechanisms in single, saturated, variable-aperture fractures.
AB  - The characterization of fractured aquifers is commonly limited to the
      methodologies developed for unconsolidated porous media aquifers, which results
      in many uncertainties. Recent work indicates that fractured rocks remove more
      particulates than they are conventionally credited for. This research was
      designed to quantify the number of Escherichia coli RS2-GFP retained in single,
      saturated, variable-aperture fractures extracted from the natural environment.
      Conservative solute and E. coli RS2-GFP tracer experiments were used to elucidate
      the relationships between dominant retention mechanisms, aperture field
      characteristics, and flow rate. A non-destructive method of determining a
      surrogate measure of a coefficient of variation (COV(S)) for each fracture was
      used to better understand the transport behaviour of E. coli RS2-GFP. The results
      from this research all point to the importance of aperture field characterization
      in understanding the fate and transport of contaminants in fractured aquifers.
      The mean aperture was a very important characteristic in determining particulate
      recovery, so were matrix properties, COV(s), and flow rate. It was also
      determined that attachment is a much more significant retention mechanism than
      straining under the conditions employed in this research. Finally, it was
      demonstrated that the dominant retention mechanism in a fracture varies depending
      on the specific discharge. An improved understanding of the mechanisms that
      influence the fate and transport of contaminants through fractures will lead to
      the development of better tools and methodologies for the characterization of
      fractured aquifers, as well as the ability to manipulate the relevant mechanisms
      to increase or decrease retention, depending on the application.

PMID- 23127623
TI  - Speciation of heavy metals in River Rhine.
AB  - Chemical speciation of Zn, Cu, Ni, Cd and Pb in River Rhine was studied by
      measuring free ion concentration and distribution in nanoparticles, and by
      comparing the measurement with speciation modeling. Concentrations of free metal
      ions were determined in situ using Donnan Membrane Technique (DMT). The
      percentage of free over total (filtered) metal concentration is 52%, 33%, 2.6%,
      0.48% and 0.12% for respectively Zn, Cd, Ni, Pb and Cu, i.e. the degree of metal
      complexation in the river is the lowest for Zn and the highest for Cu. Metals in
      1-300 nm particles were analyzed using Asymmetric Flow Field Flow Fractionation
      (AsF-FFF), but the overall recovery is quite low. The nano-sized Cu detected is
      mainly associated with DOM of 1-5 nm, whereas Pb and Zn are dominantly associated
      with particles of iron hydroxides and clay of larger size (30-100 nm). Free ion
      concentrations calculated with the speciation modeling are in good agreement with
      the measurements, except for Pb. Based on the model, DOM-bound is the most
      important complexed form for Cu and Cd, whereas formation of (bi)carbonate and
      EDTA complexes are more important for Ni and Zn. Adsorption of Pb to DOM is
      probably overestimated by the model, whereas Pb adsorption to iron hydroxides is
      underestimated.

PMID- 23127624
TI  - Evaluation of triclosan and triclocarban at river basin scale using monitoring
      and modeling tools: implications for controlling of urban domestic sewage
      discharge.
AB  - Triclosan (TCS) and triclocarban (TCC) are two commonly used personal care
      products. They may enter into aquatic environments after consumption and pose
      potential risks to aquatic organisms. We investigated the occurrence and fate of
      TCS and TCC in five large rivers (the Liao River, Hai River, Yellow River,
      Zhujiang River and Dongjiang River) in China, and compared the monitoring data
      with the predicted results from Level III fugacity modeling. TCS and TCC were
      detected in the five large rivers with the detection frequencies of 100% or close
      to 100% in surface water and sediments of almost every river. TCS and TCC were
      found at concentrations of up to 478 ng/L and 338 ng/L in surface water, and up
      to 1329 ng/g and 2723 ng/g in sediments. Cluster analysis indicated that the
      sites with higher concentrations were usually located in or near urban area.
      Meanwhile, principal component analysis also suggested that the mass inventories
      of TCS and TCC in water and sediment were significantly influenced by the factors
      such as the total or untreated urban domestic sewage discharge at river basin
      scale. The concentrations and mass inventories from the fugacity modeling were
      found at the same order of magnitude with the measured values, suggesting that
      the fugacity modeling can provide a useful tool for evaluating the fate of TCS
      and TCC in riverine environments. Both monitoring and modeling results indicated
      that the majority of mass inventories of TCS and TCC were stored into sediment,
      which could be a potential pollution source for river water. The wide presence of
      TCS and TCC in these large rivers of China implies that better controlling of
      urban domestic sewage discharge is needed.

PMID- 23127625
TI  - Mechanical characterization of human aortas from pressurization testing and a
      paradigm shift for circumferential residual stress.
AB  - Material properties needed for accurate stress analysis of the human aorta are
      still incompletely known, especially as many reports have ignored the presence of
      residual stresses in the aortic wall. To contribute new material regarding these
      issues, we carried out measurements and pressurization testing on ascending,
      thoracic and abdominal aortic samples from 24 human subjects aged 38-77 years,
      and evaluated the opening angle describing the circumferential residual stress
      level present in the aorta. We determined material constants for the aorta by
      gender, anatomic location and age group, according to a simple phenomenological
      constitutive model. The unpressurized aortic radius positively correlated with
      age, and the circumferential and longitudinal stretch ratios under systemic
      pressure negatively correlated with age, confirming the known enlargement and
      stiffening of the aorta with aging. The opening angle was measured to range from
      a minimum of 89 degrees  to above 360 degrees  for extreme cases. For given
      aortic dimensions and material properties, analysis of the in vivo
      circumferential and longitudinal mural stress distributions indicated a profound
      influence of the opening angle. For instance, in the thoracic aorta of males aged
      38-66, opening angles in the range of 0 degrees  to 80 degrees  (resp. 60 degrees
      ) may equalize the gradient of in vivo circumferential (resp. longitudinal)
      stress between the inner and outer layers of the aorta, as commonly expected;
      however, opening angles above 160 degrees  (resp. 120 degrees ) may cause the
      gradient of circumferential (resp. longitudinal) stress to reverse and increase
      compared to the case without residual stress, putting the maximum stresses toward
      the adventitia instead of the intima. Even though the analysis of the aortic wall
      excluded possible longitudinal residual stresses as well as material
      inhomogeneities, such as constitutive differences between the intimal, medial and
      adventitial layers, the experimental data reported herein are important to aortic
      modeling at large and the better understanding of aortic pathophysiology in
      particular.

PMID- 23127626
TI  - Phenomenological consequences of sectioning and bathing on passive muscle
      mechanics of the New Zealand white rabbit tibialis anterior.
AB  - Skeletal muscle tissue provides support and mobility of the musculoskeletal
      system. Numerical modeling of muscle tissue aids in understanding disease
      pathophysiology, however, the effectiveness is dependent on accurately accounting
      for various tissue phenomena. Muscle modeling is made difficult due to the
      multitude of constituents that contribute to elastic and viscous mechanisms.
      Often, deterministic single fiber or fiber bundle studies are undertaken to
      examine these contributions. However, examination of whole, intact and
      structurally altered tissue and comparison to findings at the myofibril scale can
      help elucidate tissue mechanics. Stress relaxation tests at 10% strain were
      performed on 28 New Zealand White rabbit's tibialis anterior muscles for whole,
      intact muscle and sub-sectioned muscle samples. Additionally, to aid in examining
      viscous effects, sub groups were tested with and without a phosphate buffered
      saline bath. The steady-state elastic modulus was not significantly different
      between groups. Interestingly, sectioning did result in a negative Poisson's
      ratio following tensile loading. Additionally, sectioning resulted in altering
      the viscous tissue response as the time to reach steady-state was significantly
      faster than whole muscle samples (p<0.05), as well as the linear relaxation rate
      from 0 to 0.1 (p<0.01), 1 to 10 (p<0.05), and 10 to 100 s (p<0.05). Bathing
      tissue resulted in a significantly greater amount of percent stress relaxation
      for whole muscle (p<0.01). These findings provide new insight into the differing
      mechanical characteristics of whole and sectioned muscle tissue.

PMID- 23127627
TI  - Mechanical and structural changes of the rat cervix in late-stage pregnancy.
AB  - Dysregulated remodeling of the cervix precedes preterm birth, a major cause of
      infant mortality and morbidity. The goal of this work was to identify changes in
      the mechanical properties of the cervix in late gestation. The tensile and load
      relaxation properties of cervices from rats 15-21 days (full term) post
      conception were measured. Stiffness and load at 25% circumferential strain
      decreased with gestational age and correlated with the initial circumference of
      the cervix. Load-relaxation curves were accurately described by a seven parameter
      quasi-linear viscoelastic model, where three parameters associated with stiffness
      and load capacity decrease with gestational age and correlate with initial
      circumference. Time-dependent parameters did not depend on age or structure.
      Mechanical properties correlated with water content, but unexpectedly not with
      measures of collagen content, solubility, or organization. Quantitative
      measurements of cervical stiffness and structure will lead to a more accurate
      description of cervical remodeling and prediction of preterm birth.

PMID- 23127628
TI  - Pipette aspiration applied to the characterization of nonhomogeneous,
      transversely isotropic materials used for vocal fold modeling.
AB  - The etiology and treatment of voice disorders are still not completely
      understood. Since the vibratory characteristics of vocal folds are strongly
      influenced by both anatomy and mechanical material properties, measurement
      methods to analyze the material behavior of vocal fold tissue are required. Due
      to the limited life time of real tissue in the laboratory, synthetic models are
      often used to study vocal fold vibrations. In this paper we focus on two topics
      related to synthetic and real vocal fold materials. First, because certain
      tissues within the human vocal folds are transversely isotropic, a fabrication
      process for introducing this characteristic in commonly used vocal fold modeling
      materials is presented. Second, the pipette aspiration technique is applied to
      the characterization of these materials. By measuring the displacement profiles
      of stretched specimens that exhibit varying degrees of transverse isotropy, it is
      shown that local anisotropy can be quantified using a parameter describing the
      deviation from an axisymmetric profile. The potential for this technique to
      characterize homogeneous, anisotropic materials, including soft biological
      tissues such as those found in the human vocal folds, is supplemented by a
      computational study.

PMID- 23127630
TI  - Reduction of load-bearing capacity of all-ceramic crowns due to cement aging.
AB  - The purpose of this study was to investigate how water aging of the resin cement
      influences the stress distribution in all-ceramic crowns and if there is an
      increase in the propensity for crown failure. The failure of all-ceramic crowns
      attributed to cement degradation was explored using a combination of experimental
      and numerical methods. Sectioned all-ceramic crown specimens were fabricated of
      IPS e.max Ceram/e.max Press (CP) and Vita VM9/Cercon zirconia (VZ), and then
      stored in either air or distilled water for 30 days. Monotonic contact loads were
      applied to fracture near the buccal cusp ridge of each sample. Deformation within
      the crown layers during loading was analyzed by means of Digital Image
      Correlation (DIC). A 3D finite element model of the restoration including veneer,
      core, cement and tooth substrate was developed to evaluate the stress
      distribution in the crowns before and after cement degradation. There was a
      significant decrease (p<0.001) in the critical fracture load and a change in the
      fracture mode after cement water absorption in the CP crowns. In contrast, there
      was no significant influence of cement aging on fracture modes and fracture loads
      (p>0.05) in the VZ crowns. Finite element analysis showed that regardless of the
      crown types, the stress distribution is identical by degradation in Young's
      modulus of the cement. However, core/substrate debonding results in a change of
      the stress distribution and a significant increase in the magnitude. Water aging
      causes reduction of stiffness and bonding strength of cement agents. Degradation
      in bonding strength and stiffness could potentially lead to stress redistribution
      in the restored crown and reduce the load-bearing capacity of all-ceramic
      restorations after years of service.

PMID- 23127629
TI  - Chondrogenesis on sulfonate-coated hydrogels is regulated by their mechanical
      properties.
AB  - Many studies have demonstrated that sulfur-containing acidic groups induce
      chondrogenesis in vitro and in vivo. Recently, it is increasingly clear that
      mechanical properties of cell substrates largely influence cell differentiation.
      Thus, the present study investigated how mechanical properties of sulfonate
      coated hydrogels influences chondrogenesis of mesenchymal stem cells (MSCs).
      Sulfonate-coated polyacrylamide gels (S-PAAm gels) which have the elastic
      modulus, E, of about 1, 15 and 150 kPa, were used in this study. MSCs cultured on
      the high stiffness S-PAAm gels (E=~150 kPa) spread out with strong expression of
      stress fibers, while MSCs cultured on the low stiffness S-PAAm gels (E=~1 kPa)
      had round shapes with less stress fibers but more cortical actins. Importantly,
      even in the absence of differentiation supplements, the lower stiffness S-PAAm
      gels led to the higher mRNA levels of chondrogenic markers such as Col2a1, Agc
      and Sox9 and the lower mRNA levels of an undifferentiation marker Sca1,
      indicating that the mechanical properties of S-PAAm gels strongly influence
      chondrogenesis. Blebbistatin which blocks myosin II-mediated mechanical sensing
      suppressed chondrogenesis induced by the low stiffness S-PAAm gels. The present
      study demonstrates that the soft S-PAAm gels effectively drive MSC chondrogenesis
      even in the absence of soluble differentiation factors and thus suggests that
      sulfonate-containing hydrogels with low stiffness could be a powerful tool for
      cartilage regeneration.

PMID- 23127631
TI  - Microstructures, aging behaviour and mechanical properties in hydrogen and
      chloride media of backward extruded Mg-Y based biomaterials.
AB  - Microstructures, aging behaviour from room temperature to 300  degrees C and
      mechanical properties in different media of backward extruded (BE) Mg-Y based
      biomaterial have been investigated. The results reveal that BE-Mg-Y based alloy
      is mainly composed of polygon-shaped grains and fine precipitates. The results of
      aging response show that BE-Mg-Y based alloy exhibits remarkable age hardening
      behaviour when the aging temperature is 200  degrees C and higher. The high
      mechanical properties of aged BE-Mg-Y based alloy are mostly associated with fine
      microstructure, solid solution strengthening and the existence of homogeneous
      precipitates. The hydrogen embrittlement dependence on the aging time is
      confirmed in BE-Mg-Y based alloy. Additionally, the strength and elongation of BE
      Mg-Y based alloy are significantly influenced by the ion concentration in media.
      These results offer some implications for understanding the reduced strength of
      Mg based implants in body environment. It is demonstrated that the temporary high
      mechanical strength in air of BE-Mg-Y based biomaterials is insufficient to
      evaluate the in vivo mechanical integrity.

PMID- 23127632
TI  - Carbon fiber reinforced PEEK Optima--a composite material biomechanical
      properties and wear/debris characteristics of CF-PEEK composites for orthopedic
      trauma implants.
AB  - BACKGROUND: The advantageous properties of carbon fiber reinforced
      polyetheretherketone (CF-PEEK) composites for use as orthopedic implants include
      similar modulus to bone and ability to withstand prolonged fatigue strain.
      METHODS: The CF-PEEK tibial nail, dynamic compression plate, proximal humeral
      plate and distal radius volar plate were compared biomechanically (by four-point
      bending, static torsion of the nail, and bending fatigue) and for wear/debris (by
      amount of the debris generated at the connection between the CF-PEEK plate and
      titanium alloy screws) to commercially available devices. RESULTS: Four-point
      bending stress of the tibial nail and dynamic and distal radius plates yielded
      characteristics similar to other commercially available devices. The distal volar
      plate bending structural stiffness of the CF-PEEK distal volar plate was 0.542
      Nm2 versus 0.376 Nm2 for the DePuy's DVR anatomic volar plate. The PHILOS
      proximal humeral internal locking system stainless steel plate was much stronger
      (6.48 Nm2) than the CF-PEEK proximal humeral plate (1.1 Nm2). Tibial nail static
      torsion testing showed similar properties to other tested nails (Fixion, Zimmer
      and Synthes). All tested CF-PEEK devices underwent one million fatigue cycles
      without failure. Wear test showed a lower volume of generated particles in
      comparison to the common implants in use today. INTERPRETATION: Thus, these
      tested implants were similar to commercially used devices and can be recommended
      for use as implants in orthopedic surgery.

PMID- 23127634
TI  - Debonding of porous coating of a threaded acetabular component: retrieval
      analysis.
AB  - This report presents a case of debonding of plasma sprayed porous titanium
      coating from a threaded acetabular component which caused aseptic loosening of
      the implant. Weight bearing after delamination caused abrasive damage of the
      acetabular shell, and particles of the coating embedded in the acetabular liner.
      Microscopic examination of periprosthetic tissues showed presence of metal
      particles and macrophage infiltration. Despite microscopic examination of the
      retrieved component the cause of debonding remains unclear.

PMID- 23127633
TI  - Deformationally dependent fluid transport properties of porcine coronary arteries
      based on location in the coronary vasculature.
AB  - OBJECTIVE: Understanding coronary artery mass transport allows researchers to
      better comprehend how drugs or proteins move through, and deposit into, the
      arterial wall. Characterizing how the convective component of transport changes
      based on arterial location could be useful to better understand how molecules
      distribute in different locations in the coronary vasculature. METHODS AND
      RESULTS: We measured the mechanical properties and wall fluid flux transport
      properties of de-endothelialized (similar to post-stenting or angioplasty) left
      anterior descending (LADC) and right (RC) porcine coronary arteries along their
      arterial lengths. Multiphoton microscopy was used to determine microstructural
      differences. Proximal LADC regions had a higher circumferential stiffness than
      all other regions. Permeability decreased by 198% in the LADC distal region
      compared to other LADC regions. The RC artery showed a decrease of 46.9% from the
      proximal to middle region, and 51.7% from the middle to distal regions. The
      porosity increased in the intima between pressure states, without differences
      through the remainder of the arterial thickness. CONCLUSIONS: We showed that the
      permeabilities and mechanical properties do vary in the coronary vasculature.
      With variations in mechanical properties, overexpansion of stents can occur more
      easily while variations in permeability may lead to altered transport based on
      location.

PMID- 23127635
TI  - The anisotropic mechanical behaviour of passive skeletal muscle tissue subjected
      to large tensile strain.
AB  - The passive mechanical properties of muscle tissue are important for many
      biomechanics applications. However, significant gaps remain in our understanding
      of the three-dimensional tensile response of passive skeletal muscle tissue to
      applied loading. In particular, the nature of the anisotropy remains unclear and
      the response to loading at intermediate fibre directions and the Poisson's ratios
      in tension have not been reported. Accordingly, tensile tests were performed
      along and perpendicular to the muscle fibre direction as well as at 30 degrees ,
      45 degrees  and 60 degrees  to the muscle fibre direction in samples of
      Longissimus dorsi muscle taken from freshly slaughtered pigs. Strain was measured
      using an optical non-contact method. The results show the transverse or cross
      fibre (TT') direction is broadly linear and is the stiffest (77 kPa stress at a
      stretch of 1.1), but that failure occurs at low stretches (approximately
      lambda=1.15). In contrast the longitudinal or fibre direction (L) is nonlinear
      and much less stiff (10 kPa stress at a stretch of 1.1) but failure occurs at
      higher stretches (approximatelylambda=1.65). An almost sinusoidal variation in
      stress response was observed at intermediate angles. The following Poisson's
      ratios were measured: VLT=VLT'=0.47, VTT'=0.28 and VTL=0.74. These observations
      have not been previously reported and they contribute significantly to our
      understanding of the three dimensional deformation response of skeletal muscle
      tissue.

PMID- 23127636
TI  - Chitosan/Riboflavin-modified demineralized dentin as a potential substrate for
      bonding.
AB  - Previous studies have suggested different approaches to modify dentin collagen
      for potential improvement in bonding to dentin. Here, we are proposing a new
      approach to reinforce dentin collagen fibrils network by chitosan as a
      reinforcement phase and UVA-activated riboflavin as crosslinking agent within
      clinically acceptable time-frame as potential substrate for bonding. The effect
      of modifying demineralized dentin substrates with chitosan/riboflavin, with a
      gradual increase in chitosan content, was investigated by SEM, nano-indentation,
      conventional-mechanical testing and hydroxyproline (HYP) release at
      collagenolytic and/or hydrolytic challenges. The resin/dentin interface
      morphology, immediate bond strength and short-term bond durability were also
      investigated using etch-and-rinse dentin adhesive. Modification with
      chitosan/riboflavin increased the mechanical properties, enhanced the mechanical
      stability of demineralized dentin substrates against hydrolytic and/or
      collagenolytic degradation challenges and decreased HYP release with collagenase
      exposure. When chitosan was added to riboflavin at 20%v/v ratio, significant
      improvement in bond strength at 24 h and 6 months in distilled water was found
      indicating the positive dual effect on bonding to dentin. With the gradual
      increase in chitosan content, obliteration of interfibrillar-spaces that might
      adversely affect bonding to dentin was found. Although it has a synergetic
      effect, chitosan content is crucial for any subsequent application in adhesive
      dentistry.

PMID- 23127637
TI  - Self-reinforced composites of hydroxyapatite-coated PLLA fibers: fabrication and
      mechanical characterization.
AB  - Self-reinforced composites (SRCs) are materials where both the matrix and fiber
      reinforcing phase are made up of the same polymer. Improved bonding can be
      achieved with self-reinforced composites compared to traditional dual-polymer,
      fiber-reinforced composites owing to the identical chemistry of the components in
      SRCs. Bonding between the fiber and matrix phase is an important factor in
      applications where mechanical stability is required, such as in the field of bone
      repair. In this study, we prepared bioabsorbable poly(L-lactic
      acid)/hydroxyapatite (PLLA/HA) self-reinforced composites via a three-step
      process that includes surface etching of the fiber, the deposition of the HA
      coating onto the PLLA fibers through immersion in simulated body fluid (SBF), and
      hot compaction molding. Although coated with a layer of HA, self-reinforced
      composites were successfully generated by hot compaction. The effects of
      compaction time (15 and 30 min), compaction temperature (140, 150, 155, 160, 165,
      and 170  degrees C), and HA wt% (0, 5, 10, and 15 wt%) on flexural mechanical
      properties were studied. Mechanical test results indicated that in unfilled (no
      HA) PLLA SRCs, compaction time and temperature increased the flexural modulus of
      the composites tested. Based on the results obtained for unfilled composites, a
      single compaction time and temperature condition of 15 min and 170  degrees C
      were selected to study the effect of HA loading on the composite mechanical
      properties. HA was successfully loaded onto the fibers at 0, 5, 10, and 15 wt%
      before hot compaction and was found to significantly increase flexural modulus
      (P=0.0001). Modulus values ranged from 8.3 GPa+/-0.5 (0 wt% HA) to 9.7 GPa+/-0.6
      (15 wt% HA). Microscopy results suggest that the HA in these composites forms a
      nodular-like structure along the fibers, which allows polymer-polymer contact yet
      prevents longitudinal shear. The procedure used successfully generated composites
      with flexural moduli near the lower range of bone that may have a possible
      clinical use for load-bearing bone-fixation devices.

PMID- 23127638
TI  - Application of viscoelastic fracture model and non-uniform crack initiation at
      clinically relevant notches in crosslinked UHMWPE.
AB  - The mechanism of crack initiation from a clinically relevant notch is not well
      understood for crosslinked ultra high molecular weight polyethylene (UHMWPE) used
      in total joint replacement components. Static mode driving forces, rather than
      the cyclic mode conditions typically associated with fatigue processes, have been
      shown to drive crack propagation in this material. Thus, in this study, crack
      initiation in a notched specimen under a static load was investigated. A video
      microscope was used to monitor the notch surface of the specimen and crack
      initiation time was measured from the video by identifying the onset of crack
      initiation at the notch. Crack initiation was considered using a viscoelastic
      fracture theory. It was found that the mechanism of crack initiation involved
      both single layer and a distributed multi-layer phenomenon and that multi-layer
      crack initiation delayed the crack initiation time for all loading conditions
      examined. The findings of this study support that the viscoelastic fracture
      theory governs fracture mechanics in crosslinked UHMWPE. The findings also
      support that crack initiation from a notch in UHMWPE is a more complex phenomenon
      than treated by traditional fracture theories for polymers.

PMID- 23127640
TI  - Contact angle study of blood dilutions on common microchip materials.
AB  - Biocompatible polymers are commonly used to fabricate microfluidic channels for
      the study of biological flows such as blood microflows. The most common of these
      materials is polydimethylsiloxane (PDMS) which is very hydrophobic. Oxygenated
      plasma is advocated to treat the PDMS with reported decreases in contact angle
      i.e. increase the hydrophilicity of the material in order to make the liquid flow
      easily. All contact angle studies have been reported with water. Here the contact
      angles of blood suspensions, in saline and native plasma, are compared to each
      other and water on common microfluidic chip materials. The hydrophilic effect of
      plasma-treatment on PDMS is not found to be as significant with blood suspensions
      as it is with water. Red blood cells suspended in native plasma are found to have
      a greater contact angle than those suspended in saline.

PMID- 23127639
TI  - Localized sclerotic bone response demonstrated reduced nanomechanical creep
      properties.
AB  - Sclerosis (tissue hardening) development is a common occurrence in slow growing
      or benign osteolytic lesions. However, there is lack of knowledge on the
      mechanical and material property changes associated with sclerotic bone response.
      The immune system is postulated to play a relevant role in evoking sclerotic bone
      responses. In this study, localized sclerotic response in an immunocompetent
      model of Walker 256 breast carcinoma in SD rats showed an apparent increase in
      new reactive bone formation. Sclerotic rat femurs had significant increases in
      bone mineral density (BMD), bone mineral content (BMC), bone volume fraction
      (BV/TV), bone surface density (BS/TV), trabecular number (Tb.N) and a significant
      decrease in trabecular separation (Tb.Sp) and structural model index (SMI) as
      compared to control rat femurs. Significantly reduced creep responses (increased
      eta) were observed for both trabecular and cortical bone in sclerotic bones while
      no significant difference was observed in elastic modulus (E) and hardness (H)
      values. Therefore, we conclude that viscoelastic creep property using
      nanoindentation would serve as a more sensitive indicator of localized bone
      modeling than elastic properties. Moreover, reduced viscoelasticity can
      contribute towards increased microcrack propagation and therefore reduced
      toughness. Since significant positive correlations between elastic properties (E)
      and (H) with viscosity (eta) were also observed, our results indicate that
      sclerotic response of bone metastasis would cause reduced toughness (increased
      eta) with stiffening of material (increased E and H).

PMID- 23127641
TI  - Mechanical characterization of brain tissue in tension at dynamic strain rates.
AB  - Mechanical characterization of brain tissue at high loading velocities is crucial
      for modeling Traumatic Brain Injury (TBI). During severe impact conditions, brain
      tissue experiences compression, tension and shear. Limited experimental data is
      available for brain tissue in extension at dynamic strain rates. In this
      research, a High Rate Tension Device (HRTD) was developed to obtain dynamic
      properties of brain tissue in extension at strain rates of <=90/s. In vitro
      tensile tests were performed to obtain properties of brain tissue at strain rates
      of 30, 60 and 90/s up to 30% strain. The brain tissue showed a stiffer response
      with increasing strain rates, showing that hyperelastic models are not adequate.
      Specifically, the tensile engineering stress at 30% strain was 3.1+/-0.49kPa,
      4.3+/-0.86kPa, 6.5+/-0.76kPa (mean+/-SD) at strain rates of 30, 60 and 90/s,
      respectively. Force relaxation tests in tension were also conducted at different
      strain magnitudes (10-60% strain) with the average rise time of 24ms, which were
      used to derive time dependent parameters. One-term Ogden, Fung and Gent models
      were used to obtain material parameters from the experimental data. Numerical
      simulations were performed using a one-term Ogden model to analyze hyperelastic
      behavior of brain tissue up to 30% strain. The material parameters obtained in
      this study will help to develop biofidelic human brain finite element models,
      which can subsequently be used to predict brain injuries under impact conditions
      and as a reconstruction and simulation tool for forensic investigations. 

PMID- 23127642
TI  - Experimental mechanical characterization of abdominal organs: liver, kidney &
      spleen.
AB  - Abdominal organs are the most vulnerable body parts during vehicle trauma,
      leading to high mortality rate due to acute injuries of liver, kidney, spleen and
      other abdominal organs. Accurate mechanical properties and FE models of these
      organs are required for simulating the traumas, so that better designing of the
      accident environment can be done and the organs can be protected from severe
      damage. Also from biomedical aspect, accurate mechanical properties of organs are
      required for better designing of surgical tools and virtual surgery environments.
      In this study porcine liver, kidney and spleen tissues are studied in vitro and
      hyper-elastic material laws are provided for each. 12 porcine kidneys are used to
      perform 40 elongation tests on renal capsule and 60 compression tests on renal
      cortex, 5 porcine livers are used to perform 45 static compression tests on liver
      parenchyma and 5 porcine spleens are used to carry out 20 compression tests. All
      the tests are carried out at a static speed of 0.05 mm/s. A comparative analysis
      of all the results is done with the literature and though the results are of same
      order of magnitude, a slight dissonance is observed for the renal capsule. It is
      also observed that the spleen is the least stiff organ in the abdomen whereas the
      kidney is the stiffest. The results of this study would be essential to develop
      the FE models of liver, kidney and spleen which can be further used for impact
      biomechanical and biomedical applications.

PMID- 23127643
TI  - Compression-bending of multi-component semi-rigid columns in response to axial
      loads and conjugate reciprocal extension-prediction of mechanical behaviours and
      implications for structural design.
AB  - The mathematical modelling of column buckling or beam bending under an axial or
      transverse load is well established. However, the existent models generally
      assume a high degree of symmetry in the structure of the column and minor
      longitudinal and transverse displacements. The situation when the column is made
      of several components with different mechanical properties asymmetrically
      distributed in the transverse section, semi-rigid, and subjected to multiple
      axial loads with significant longitudinal and transverse displacements through
      compression and bending has not been well characterised. A more comprehensive
      theoretical model allowing for these possibilities and assuming a circular arc
      contour for the bend is developed, and used to establish the bending axes,
      balance between compression and bending, and equivalent stiffness of the column.
      In certain situations, such as with pull cable catheters commonly used for
      minimally invasive surgical procedures, the compression loads are applied via
      cables running through channels inside a semi-rigid column. The model predicts
      the mathematical relationships between the radius of curvature of the bend and
      the tension in and normal force exerted by such cables. Conjugate extension with
      reciprocal compression-bending is a special structural arrangement for a semi
      rigid column such that extension of one segment is linked to compression-bending
      of another by inextensible cables running between them. Leads are cords
      containing insulated electrical conductor coil and cables between the heart
      muscle and cardiac implantable electronic devices. Leads can behave like pull
      cable catheters through differential component pulling, providing a possible
      mechanism for inside-out abrasion and conductor cable externalisation. Certain
      design features may predispose to this mode of structural failure.

PMID- 23127644
TI  - Is the ovine intervertebral disc a small human one? A finite element model study.
AB  - The sheep is one of the most frequently used animal models for experimental
      intervertebral disc research questions. Although there are large differences in
      size between human and ovine discs, recent in vivo and in vitro studies indicate
      similarities in the internal disc stresses. The present finite element model
      study, therefore, intended to detect the parameters that, despite the different
      geometry, ensure mechanical comparability between both species. At first, a
      finite element model of the human L4-L5 lumbar intervertebral disc was developed.
      The predicted displacement and nucleus pressure response were validated with
      experimental in vivo and in vitro data. Starting with adapting the model geometry
      from the human to the ovine disc, several material and biochemical parameters,
      which might contribute to the preservation of the mechanical disc response across
      both species, were successively adapted to ovine properties. Replacing the
      geometry yielded a substantially higher disc stiffness and lower nucleus pressure
      compared to in vitro measurements performed on ovine discs. Additional reduction
      of annulus and nucleus elasticity led to an improved correlation between model
      predictions and measurements. Changes in the glycosaminoglycan content and
      endplate permeability improved the predicted pressure, but only slightly affected
      the displacement response. Only the combination of all parameters resulted in a
      good agreement between the predictions and measurements. This study demonstrated
      that there are profound differences between model predictions and in vitro
      results if an ovine simulation is run with human material properties. However,
      once the species-specific material properties are included, the predictions fit
      the in vitro results. Therefore, it seems that the human and ovine disc is
      functionally adapted to produce similar internal stresses, despite the large
      variation in geometry.

PMID- 23127645
TI  - Aged garlic extract restores nitric oxide bioavailability in cultured human
      endothelial cells even under conditions of homocysteine elevation.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Supplementation with aged garlic extract (AGE)
      has been shown to restore impaired endothelium-dependent vasodilator response in
      subjects with acutely elevated plasma homocysteine (Hcy) levels after an oral
      methionine load and in patients with chronic coronary artery disease. Moreover,
      AGE has been shown to inhibit the progression of coronary calcifications in
      patients with coronary artery disease. The molecular mechanisms, by which AGE
      preserves endothelial function is unknown. Our objective was to explore whether
      AGE preserves endothelial nitric oxide (NO) output even under conditions of
      elevated Hcy levels by preventing oxidative inactivation of the NO synthase
      cofactor tetrahydrobiopterin. MATERIAL AND METHODS: Endothelial (EA.hy 926) cells
      were incubated with hypoxanthine, aminopterin, thymidine and methionine (HAT/MET)
      to increase cellular Hcy levels, and with and without AGE. Agonist stimulated NO
      output was measured using the fluorescent probe DAF-2, and cellular thiol levels
      (Hcy, cysteine, reduced and oxidized glutathione) and cellular
      tetrahydrobiopterin levels were measured by high performance liquid
      chromatography. RESULTS: HAT/MET incubation resulted in significantly increased
      cellular Hcy levels, unaffected by coincubation with AGE. Elevated Hcy went along
      with significantly decreased NO output (to 34.4 +/- 4.4% of control) and levels
      of tetrahydrobiopterin (from 4.67 +/- 2.17 to 2.17 +/- 0.97 pmol/mg). Incubation
      with AGE (5mg/mL) in HAT/MET-treated cells prevented the declines in NO output
      and tetrahydrobiopterin levels. AGE increased cellular levels of cysteine and
      total glutathione, and prevented glutathione and tetrahydrobiopterin oxidation
      induced by elevated Hcy. CONCLUSION: Incubation with AGE preserved normal NO
      output from endothelial cells even under conditions of elevated Hcy levels by
      increasing cellular thiol antioxidant and prevention of tetrahydrobiopterin
      oxidation. This suggests that AGE might be useful in the prevention of
      endothelial dysfunction.

PMID- 23127646
TI  - Purification and characterization of a novel antithrombotic peptide from
      Scolopendra subspinipes mutilans.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The centipede has been prescribed for the
      treatment of cardiovascular diseases in Korea, China and other Far Eastern Asian
      countries for several hundred years. MATERIALS AND METHODS: A novel
      antithrombotic peptide was isolated from Scolopendra subspinipes mutilans using a
      combination of ultrafiltration, Sephadex G-50 column, Source 15Q anion exchange
      column and RP-HPLC C18 column. RESULTS: The molecular mass of the purified
      peptide is 346Da measured by Electrospray Ionization Mass Spectrometry (ESI-MS).
      The primary structure of the peptide is Ser-Gln-Leu (SQL) determined by Edman
      degradation. SQL potently prolonged the activated partial thromboplastin time
      (aPTT), and inhibited platelet aggregation. CONCLUSIONS: These results help to
      clarify the mechanism of the antithrombotic activity of the centipede for
      effective treatment of cardiovascular and cerebrovascular diseases.

PMID- 23127648
TI  - New antiplasmodial alkaloids from Stephania rotunda.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Stephania rotunda Lour. (Menispermaceae) is a
      creeper growing in many countries of Asia and commonly found in the mountainous
      areas of Cambodia. As a folk medicine, it has been mainly used for the treatment
      of fever and malaria. The pharmacological activity is mostly due to alkaloids.
      Thus the aim of this study is to isolate new bioactive alkaloids from Stephania
      rotunda and to evaluate their in vitro antiplasmodial activity. MATERIALS AND
      METHODS: Alkaloids were isolated and identified from dichloromethane and aqueous
      extracts using a combination of flash chromatography, high performance liquid
      chromatography, mass spectrometry and nuclear magnetic resonance. The purified
      compounds were tested for in vitro antiplasmodial activity on chloroquine
      resistant W2 strain of Plasmodium falciparum. RESULTS: A new aporphine alkaloid
      named vireakine (2) along with two known alkaloids stephanine (1) and
      pseudopalmatine (8), described for the first time in Stephania rotunda, and
      together five known alkaloids tetrahydropalmatine (3), xylopinine (4), roemerine
      (5), cepharanthine (6) and palmatine (7) were isolated and identified. The
      structure of the new alkaloid was established on the basis of 1D and 2D NMR
      experiments and mass spectrometry. The compounds were evaluated for their in
      vitro antiplasmodial and cytotoxic activities. All tested compounds showed
      significant antiplasmodial activities with IC(50) ranged from 1.2 MUM to 52.3 MUM
      with a good selectivity index for pseudopalmatine with IC(50) of 2.8 MUM against
      W2 strain of Plasmodium falciparum and IC(50)>25 MUM on K562S cells. CONCLUSIONS:
      This study provides evidence to support the use of Stephania rotunda for the
      treatment of malaria and/or fever by the healers. Alkaloids of the tuber
      exhibited antiplasmodial activity and particularly cepharanthine and
      pseudopalmatine.

PMID- 23127647
TI  - The cytotoxic effects of Scilla nervosa (Burch.) Jessop (Hyacinthaceae) aqueous
      extract on cultured HepG2 cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Bulbs of Scilla nervosa, a medicinal plant
      indigenous to Southern Africa, are traditionally used in aqueous decoctions to
      treat a diverse range of illnesses. The bulbs contain homoisoflavanones and
      stilbenoids. Little information is known about the plant's toxicity on the liver,
      a major detoxifying organ. This study investigated the effects of an aqueous
      extract of the bulbs in cultured HepG2 liver cells, a model system for
      investigating the toxicity of xenobiotics. MATERIALS AND METHODS: The
      concentration that reduced cell viability to 50% (IC(50)) after 24h treatment was
      derived. Potential mechanisms of toxicity using the IC(50) were investigated as
      changes in metabolic activity, apoptosis, oxidative damage and DNA fragmentation.
      In addition, cytochrome P450 3A4 (CYP3A4) activity, which is implicated in drug
      metabolism and interactions, was also assayed. RESULTS: Cell viability decreased
      in a concentration-dependent manner and the IC(50) was determined as 0.03 mg/mL.
      Treating the cells at the IC(50) for 24h resulted in increased intracellular ATP
      levels, no significant change in phosphatidylserine externalisation, increased
      caspase-8 activity, decreased caspase-9 activity, no significant change in
      mitochondrial membrane potential, increased lipid peroxidation, evidence for
      genotoxicity as demonstrated by DNA fragmentation, and slightly induced CYP3A4
      activity. CONCLUSION: Results suggest that liver cells are sensitive to an
      aqueous extract of the bulbs and there is an increased potential to induce
      apoptosis, oxidative stress and genotoxicity in vitro.

PMID- 23127649
TI  - Quercus cerris extracts limit Staphylococcus aureus biofilm formation.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Quercus cerris L., Fagaceae has been used in
      traditional Mediterranean medicine for numerous purposes, including anti
      infective therapies for diarrhea and wound care. AIM OF THE STUDY: To evaluate
      the anti-staphylococcal activity of fractions of ethanolic extracts of Quercus
      cerris leaf and stem/fruit samples in models for biofilm and growth inhibition.
      MATERIALS AND METHODS: Ethanolic extracts of Quercus cerris leaves and
      stems/fruits were prepared, resuspended in water and fractioned by successively
      partitioning with hexane, ethyl acetate and butanol. The ability of the fractions
      to inhibit Staphylococcus aureus biofilm formation was tested using static
      crystal violet staining methods and confocal laser scanning microscopy. Growth
      studies were conducted to determine if the diminished capacity to form a biofilm
      was related to growth inhibition. RESULTS: The butanol extracts of both the leaf
      and stem/fruit samples were the most active, and at a dose of 200 MUg/ml, the
      capacity to form a biofilm was limited to a level equivalent to that of the sarA
      mutant controls. Further examination of the impact of these fractions on
      Staphylococcus aureus growth revealed that biofilm inhibition by the leaf butanol
      fraction was due to its bacteriostatic activity. The stem/fruit butanol fraction,
      however, showed a limited impact on growth, thus demonstrating that biofilm
      inhibition in this case is not related to the bacteriostatic activity of the
      extract. CONCLUSION: Our evaluation of a medicinal plant used in Mediterranean
      ethnotherapies for infectious disease has demonstrated significant activity in
      the inhibition of staphylococcal biofilm formation with a mechanism unrelated to
      staphylococcal growth inhibition. These results contribute towards validation of
      this botanical remedy and form the groundwork for future studies in the search
      for novel biofilm inhibiting drugs.

PMID- 23127650
TI  - Effect of acute pancreatitis on the pharmacokinetics of Chinese herbal ointment
      Liu-He-Dan in anaesthetized rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Chinese herbal preparation of Liu-He-Dan ointment
      has been adapted for acute pancreatitis in external application for many years in
      West China. AIM OF THE STUDY: To investigate the effect of acute pancreatitis on
      the pharmacokinetics of Liu-He-Dan ointment in rats while it was used externally
      on belly. MATERIALS AND METHODS: Twelve male Sprague-Dawley rats were randomly
      divided into acute pancreatitis model group (n=6) and normal group as a control
      (n=6). Chinese herbal Liu-He-Dan ointment was used externally on belly. Emodin,
      rhein, aloe emodin, physcion and chrysophanol in plasma and pancreas (at 48 h)
      were detected and quantified by liquid chromatography-tandem mass spectrometry.
      Amylase in plasma were determined with iodide process. RESULTS: Among the five
      components, only emodin, aloe emodin and physcion from Liu-He-Dan were detected
      in plasma and pancreas. The absorption of each component was tended to decrease
      in acute pancreatitis group after topically management with Liu-He-Dan ointment
      on rats' abdomen. The T(max), C(max) and area under curve (AUC) of each component
      were distinctly lower in AP group than those in normal group (p<0.05). However,
      the T(1/2alpha) and mean retention time (MRT) of emodin lasted longer in acute
      pancreatitis group than those in normal group (p<0.05). There was no statistical
      difference in the MRT of aloe emodin and physcion between the two groups. Emodin
      could be detected in all rats' pancreas at 48 h in both groups, while its mean
      pancreatic concentration was higher in acute pancreatitis model group than in
      normal group (0.91 +/- 0.68, 0.41 +/- 0.36, respectively). Physcion could be
      detected in pancreas of most acute pancreatitis models, but not in normal rats.
      Aloe emodin was found in all pancreas from acute pancreatitis models while only
      one in normal group. The level of amylase in Liu-He-Dan group was obviously lower
      than that in the AP model group (p=0.0055). CONCLUSION: We concluded that acute
      pancreatitis may significantly affect the pharmacokinetics of Liu-He-Dan while
      external applied on belly, which indicated the dosage modification in AP.
      However, acute pancreatitis seems to promote the distribution of the detected
      components into pancreas. The ointment could help relieve the disease of
      pancreatitis.

PMID- 23127651
TI  - Fuzheng Huayu inhibits carbon tetrachloride-induced liver fibrosis in mice
      through activating hepatic NK cells.
AB  - AIM OF THE STUDY: Fuzheng Huayu (FZHY) is a Chinese compound herbal preparation
      which consists of six Chinese herbs. This study examines the preventative effects
      of FZHY on liver fibrosis induced by carbon tetrachloride (CCl(4)) and explores
      its possible mechanisms of action. MATERIALS AND METHODS: Liver fibrosis was
      induced in male C57BL/6N mice by injecting a 10% CCl(4) solution intraperitoneal
      twice a week for six weeks. After 6 weeks of treatment, serum ALT and AST assay,
      liver tissue histological examination and immunostaining were carried out to
      examine the liver function and fibrosis degree. The expression levels of alpha
      smooth muscle actin (SMA) were measured by quantitative real-time PCR and western
      blot. Hepatic natural killer (NK) cells were isolated from liver and evaluated by
      FACS. RESULTS: Upon pathological examination, the FZHY-treated mice showed
      significantly reduced liver damage. The expression of alpha-SMA increased
      markedly upon treatment with CCl(4) and the increase was reversed by FZHY
      treatment. FZHY treatment also enhanced the activation of hepatic NK cells and
      the production of interferon-gamma (IFN-gamma). The protective effects of FZHY
      were reversed in the mice that were depleted of NK cells by anti-ASGM-1 Ab
      treatment. CONCLUSIONS: FZHY can efficiently inhibit CCl(4)-induced liver
      fibrosis. Furthermore, the depletion of NK cells attenuates the protective
      effects of FZHY. We conclude that FZHY could be an effective drug for liver
      fibrosis, and its mechanism of action involves the activation of hepatic NK
      cells.

PMID- 23127652
TI  - Neuroprotective effects of the Chinese Yi-Qi-Bu-Shen recipe extract on injury of
      rat hippocampal neurons induced by hypoxia/reoxygenation.
AB  - OBJECTIVE: To explore the protective effects of the Chinese Yi-Qi-Bu-Shen recipe
      (YB) against neuronal injury induced by hypoxia-reoxygenation, which has shown
      beneficial effect in improving the brain function of type 2 diabetics likely
      through its antihyperglycemic, antioxidant activity, and investigate its
      mechanisms. METHODS: The bilateral hippocampus was collected from newborn rats to
      establish single cell suspension. On the 10th day, the primarily cultured
      hippocampal neurons were randomly divided into five groups: the normal group
      (NG), the hypoxia/reoxygenation group (HG), and groups protected with small,
      medium and large dosages of YB (SG, MG and LG, respectively). The YB-protected
      groups were treated with different concentrations of YB containing serum before
      reoxygenation. The metabolic rate of MTT, the malondialdehyde (MDA) content, and
      the activity of superoxide dismutase (SOD) and lactate dehydrogenase (LDH) were
      measured with assay kits. The apoptosis rate of hippocampal neurons were tested
      using flow cytometry analysis. RT-PCR was used to evaluate the mRNA expressions
      of bcl-2 and bax genes. RESULTS: The SOD activity, the cell survival rate, the
      bcl-2/bax ratio, and the bcl-2mRNA expression in the HG group were significantly
      lower (all P<0.01), but the levels of MDA and LDH, the apoptosis rate, and the
      bax mRNA expression were higher (all P<0.01) than those in the NG group. The SOD
      activity, the cell survival, the bcl-2mRNA expression, and the bcl-2/bax ratio
      were significantly higher in all of the YB-protected groups (all P<0.01), but the
      level of MDA and LDH, the apoptosis rate, and the bax mRNA expression were lower
      (P<0.01, P<0.05) than those in the HG group in a dose dependent manner.
      CONCLUSION: The YB extract has a protective effect on hippocampal neurons against
      injury induced by hypoxia/reoxygenation, through its antioxidant activity and the
      regulation of apoptosis.

PMID- 23127653
TI  - Magnolol inhibits lipopolysaccharide-induced inflammatory response by interfering
      with TLR4 mediated NF-kappaB and MAPKs signaling pathways.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Magnolia officinalis as a traditional Chinese
      herb has long been used for the treatment of anxiety, cough, headache and
      allergic diseases, and also have been used in traditional Chinese medicine to
      treat a variety of mental disorders including depression. AIM OF THE STUDY:
      Magnolol, a hydroxylated biphenyl compound isolated from Magnolia officinalis,
      has been reported to have anti-inflammatory properties. However, the underlying
      molecular mechanisms are not well understood. The aim of this study was to
      investigate the molecular mechanism of magnolol in modifying lipopolysaccharide
      (LPS)-induced signal pathways in RAW264.7 cells. MATERIAL AND METHODS: The purity
      of magnolol was determined by high performance liquid chromatography. RAW264.7
      cells were stimulated with LPS in the presence or absence of magnolol. The
      expression of proinflammatory cytokines were determined by ELISA and reverse
      transcription-PCR. Nuclear factor-kappaB (NF-kappaB), inhibitory kappa B
      (IkappaBalpha) protein, p38, extracellular signal-regulated kinase (ERK), c-Jun N
      terminal kinase (JNK) and Toll-like receptor 4 (TLR4) were determined by Western
      blot. Further analyses were performed on mTLR4 and mMD2 co-transfected HEK293
      cells. RESULTS: The result showed that the purity of magnolol used in this study
      was 100%. Magnolol inhibited the expression of TNF-alpha, IL-6 and IL-1beta in
      LPS-stimulated RAW264.7 cells in a dose-dependent manner. Western blot analysis
      showed that magnolol suppressed LPS-induced NF-kappaB activation, IkappaBalpha
      degradation, phosphorylation of ERK, JNK and P38. Magnolol could significantly
      down-regulated the expression of TLR4 stimulating by LPS. Furthermore, magnolol
      suppressed LPS-induced IL-8 production in HEK293-mTLR4/MD-2 cells. CONCLUSIONS:
      Our results suggest that magnolol exerts an anti-inflammatory property by down
      regulated the expression of TLR4 up-regulated by LPS, thereby attenuating TLR4
      mediated the activation of NF-kappaB and MAPK signaling and the release of pro
      inflammatory cytokines. These findings suggest that magnolol may be a therapeutic
      agent against inflammatory diseases.

PMID- 23127654
TI  - The antinociceptive and anti-inflammatory effects of the crude extract of
      Jatropha isabellei in a rat gout model.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Jatropha isabellei Mull Arg. (Euphorbiaceae) is a
      medicinal plant that has been used in South American folk medicine for the
      treatment of arthritic diseases, particularly gout. AIM OF THE STUDY: This study
      was designed to verify the antinociceptive, anti-inflammatory and hypouricemic
      potential of Jatropha isabellei. MATERIALS AND METHODS: Rats were orally
      administered with the crude extract (100-300 mg/kg) or a fraction that is rich in
      alkaloids (0.15 mg/kg) of Jatropha isabellei. An intra-articular (i.a.) injection
      of 50 MUl of monosodium urate (MSU) crystals (1.25mg/site) was used to generate
      the gout model to assess the effect of the treatment on nociception (thermal and
      mechanical hyperalgesia) and inflammation (oedema and neutrophil infiltration).
      The effect of Jatropha isabellei on the serum levels of uric acid was evaluated
      in a model of hyperuricaemia induced by the intraperitoneal injection of
      potassium oxonate (250 mg/kg). The side effects were analysed using an open-field
      test, gastric lesion assessment and by measuring the levels of the ALT and AST
      enzymes. RESULTS: Our study demonstrated that the crude extract of Jatropha
      isabellei and a fraction rich in alkaloids were able to prevent the thermal
      hyperalgesia, mechanical allodynia, oedema and neutrophil infiltration induced by
      intra-articular MSU injection in rats. On the other hand, treatment with Jatropha
      isabellei did not alter the uric acid levels increased by potassium oxonate in
      the hyperuricaemia model. In addition, Jatropha isabellei did not induce gastric
      lesions or liver damage and did not alter spontaneous locomotor activity.
      CONCLUSION: The crude extract of Jatropha isabellei and its fraction rich in
      alkaloid presents antinociceptive and anti-inflammatory effects in a rat gout
      model, similar to that observed after treatment with colchicine, supporting the
      traditional use of this plant in gouty patients.

PMID- 23127655
TI  - Reply to letter: How to accurately perform chest compressions (CC) according to
      CPR guidelines on mattresses of varying softness.

PMID- 23127656
TI  - Integrating forensic information in a crime intelligence database.
AB  - Since 2008, intelligence units of six states of the western part of Switzerland
      have been sharing a common database for the analysis of high volume crimes. On a
      daily basis, events reported to the police are analysed, filtered and classified
      to detect crime repetitions and interpret the crime environment. Several forensic
      outcomes are integrated in the system such as matches of traces with persons, and
      links between scenes detected by the comparison of forensic case data. Systematic
      procedures have been settled to integrate links assumed mainly through DNA
      profiles, shoemarks patterns and images. A statistical outlook on a retrospective
      dataset of series from 2009 to 2011 of the database informs for instance on the
      number of repetition detected or confirmed and increased by forensic case data.
      Time needed to obtain forensic intelligence in regard with the type of marks
      treated, is seen as a critical issue. Furthermore, the underlying integration
      process of forensic intelligence into the crime intelligence database raised
      several difficulties in regards of the acquisition of data and the models used in
      the forensic databases. Solutions found and adopted operational procedures are
      described and discussed. This process form the basis to many other researches
      aimed at developing forensic intelligence models. 

PMID- 23127657
TI  - Development of an automated data processing method for sample to sample
      comparison of seized methamphetamines.
AB  - The information about the sources of supply, trafficking routes, distribution
      patterns and conspiracy links can be obtained from methamphetamine profiling. The
      precursor and synthetic method for the clandestine manufacture can be estimated
      from the analysis of minor impurities contained in methamphetamine. Also, the
      similarity between samples can be evaluated using the peaks that appear in
      chromatograms. In South Korea, methamphetamine was the most popular drug but the
      total seized amount of methamphetamine whole through the country was very small.
      Therefore, it would be more important to find the links between samples than the
      other uses of methamphetamine profiling. Many Asian countries including Japan and
      South Korea have been using the method developed by National Research Institute
      of Police Science of Japan. The method used gas chromatography-flame ionization
      detector (GC-FID), DB-5 column and four internal standards. It was developed to
      increase the amount of impurities and minimize the amount of methamphetamine.
      After GC-FID analysis, the raw data have to be processed. The data processing
      steps are very complex and require a lot of time and effort. In this study,
      Microsoft Visual Basic Application (VBA) modules were developed to handle these
      data processing steps. This module collected the results from the data into an
      Excel file and then corrected the retention time shift and response deviation
      generated from the sample preparation and instruments analysis. The developed
      modules were tested for their performance using 10 samples from 5 different
      cases. The processed results were analyzed with Pearson correlation coefficient
      for similarity assessment and the correlation coefficient of the two samples from
      the same case was more than 0.99. When the modules were applied to 131 seized
      methamphetamine samples, four samples from two different cases were found to have
      the common origin and the chromatograms of the four samples were appeared
      visually identical. The developed VBA modules could process raw data of GC-FID
      very quickly and easily. Also, they could assess the similarity between samples
      by peak pattern recognition using whole peaks without spectral identification of
      each peak that appeared in the chromatogram. The results collectively suggest
      that the modules would be useful tools to augment similarity assessment between
      seized methamphetamine samples.

PMID- 23127658
TI  - Forensic autopsies in a naturalistic setting in Norway: autopsy rates and
      toxicological findings.
AB  - Autopsies can give valuable information about the cause of death, and represent
      an important tool for obtaining valid cause of death statistics. In particular,
      they may shed light on the circumstances of death in ambiguous and criminal
      cases. To address the need for information on current autopsy practices, forensic
      autopsy rates in two counties in Central Norway over the period 2007-2009 were
      assessed. To investigate toxicological findings that could possibly remain
      undisclosed without the performance of an autopsy, the impact of alcohol and
      drugs in forensic autopsy cases from this material was evaluated. The total
      forensic autopsy rate in this material was 3%. The forensic autopsy rates were
      low for natural deaths (1%), accidental falls (12%) and the heterogeneous
      category "other accidents" (21%), relatively high for accidental poisonings
      (84%), and less than adequate for road traffic accidents (57%). For suicides the
      forensic autopsy rate was 63%, and for recognized homicides 100%. The total
      forensic autopsy rate was higher for men than for women (5% vs. 2%), and
      decreased with age, being 38% in the age group <30 years, 23% in the age group 30
      59 years, and 1% in the age group >59 years. Despite that Norwegian legislation
      and regulations regarding forensic autopsy requests are national, the forensic
      autopsy rates were generally lower in the county of Nord-Trondelag than in Sor
      Trondelag, with most striking differences in suicide deaths (11% vs. 91%) and
      road traffic accidents (46% vs. 67%). This illustrates how autopsy rates, and
      possibly cause of death registries, might be susceptible to the influence of
      regional variations in law enforcement, with possible consequences for the
      quality and validity of cause of death statistics. Of the forensic autopsy cases
      where toxicological analysis was performed (361 of 364 cases) a total of 71% had
      positive toxicology results; 12% were positive for alcohol only, 44% were
      positive for drugs only, and 15% were positive for both alcohol and drugs. The
      toxicology results suggest that alcohol and drugs are important factors in sudden
      unexpected deaths, and that a thorough and comprehensive toxicological analysis
      is called for when investigating these deaths. Mean BAC in alcohol positive
      forensic autopsy cases was 1.70/00 (median 1.60/00, range 0.29-4.10/00). The
      average number of substances detected in toxicology positive cases was 2.6
      (median 2, range 1-10). The by far most frequently detected classes of substances
      were (1) benzodiazepines, (2) opioids and (3) alcohol.

PMID- 23127659
TI  - Clarification of route specific impurities found in methylamphetamine synthesised
      using the Birch method.
AB  - This paper focuses on the determination of route specific impurities produced
      when methylamphetamine is synthesised using the Birch reduction. Previous work
      available in the scientific literature reported only one route specific impurity
      using ephedrine hydrochloride as the starting material. In this paper we
      investigated the impurity profiles of methylamphetamine produced from both the
      salt and base forms of ephedrine and pseudoephedrine. A new previously unreported
      route specific impurity was revealed as was the potential absence of the
      previously reported impurity in the profile of samples prepared from the free
      base.

PMID- 23127660
TI  - Synthesis and impurity profiling of MDMA prepared from commonly available
      starting materials.
AB  - This work examines the synthesis of 3,4-methylenedioxy-N-methylamphetamine (MDMA)
      from common starting materials that may be utilised by clandestine laboratory
      operators. Piperonal was prepared from two common starting materials, piperine
      (from pepper) and vanillin (a common flavouring). Piperine was converted to
      piperonal by ozonolysis and oxidative cleavage with potassium permanganate and
      tetrahydrofuran. Vanillin was converted to piperonal by demethylation with
      pyridine and aluminium chloride followed by methylenation with dichloromethane.
      The resulting piperonal samples were converted via a commonly encountered route
      to MDMA. The impurities that indicate a particular route were identified and the
      feasibility of each method was also assessed.

PMID- 23127661
TI  - Metabolite to parent drug concentration ratios in hair for the differentiation of
      tramadol intake from external contamination and passive exposure.
AB  - Tramadol was found in a man's hair sample during an abstinence test necessary to
      regain his driving license. The suspect denied having taken tramadol claiming
      external contamination as the reason for the positive result, as he was working
      in a tramadol production company. Nevertheless, low concentrations of both major
      metabolites, N-desmethyltramadol (NDMT) and O-desmethyltramadol (ODMT), were
      found in hair (180 and 6 pg/mg hair, respectively). To assess this case, tramadol
      concentrations and metabolite to parent drug concentration ratios were determined
      in hair samples of 75 patients taking tramadol and of eight employees working in
      the production and laboratory site of the same company. Additionally, wash water
      used for decontaminating hair was analyzed for both groups, patients and
      employees. Analysis of hair sample extracts was performed by LC-MS/MS using
      multiple reaction monitoring (MRM), information dependent acquisition (IDA) and
      enhanced product ion scan (EPI). High variations of metabolite to parent drug
      concentration ratios in hair samples of patients were observed. Differences in
      NDMT and ODMT to tramadol concentration ratios were found when comparing the
      cohort of patients to employees. The suspect could be included in the cohort of
      employees considering the ODMT to tramadol concentration ratio in hair and
      tramadol concentration ratio in wash water versus hair. Metabolite to parent drug
      concentration ratios of hair samples may represent a helpful tool for the
      differentiation of tramadol intake versus external contamination. Ratios of
      tramadol concentrations in wash water versus the subjects' hair may provide
      additional information for case assessments.

PMID- 23127663
TI  - Dead space: a risk factor we did not see.

PMID- 23127662
TI  - Metabolomic analysis of two different models of delayed preconditioning.
AB  - Recently we described an ischemic preconditioning induced by repetitive coronary
      stenosis, which is induced by 6 episodes of non-lethal ischemia over 3 days, and
      which also resembles the hibernating myocardium phenotype. When compared with
      traditional second window of ischemic preconditioning using cDNA microarrays,
      many genes which differed in the repetitive coronary stenosis appeared targeted
      to metabolism. Accordingly, the goal of this study was to provide a more in depth
      analysis of changes in metabolism in the different models of delayed
      preconditioning, i.e., second window and repetitive coronary stenosis. This was
      accomplished using a metabolomic approach based on liquid chromatography-mass
      spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) techniques.
      Myocardial samples from the ischemic section of porcine hearts subjected to both
      models of late preconditioning were compared against sham controls.
      Interestingly, although both models involve delayed preconditioning, their
      metabolic signatures were radically different; of the total number of metabolites
      that changed in both models (135 metabolites) only 7 changed in both models, and
      significantly more, p<0.01, were altered in the repetitive coronary stenosis
      (40%) than in the second window (8.1%). The most significant changes observed
      were in energy metabolism, e.g., phosphocreatine was increased 4 fold and
      creatine kinase activity increased by 27.2%, a pattern opposite from heart
      failure, suggesting that the repetitive coronary stenosis and potentially
      hibernating myocardium have enhanced stress resistance capabilities. The improved
      energy metabolism could also be a key mechanism contributing to the
      cardioprotection observed in the repetitive coronary stenosis and in hibernating
      myocardium. This article is part of a Special Issue entitled "Focus on Cardiac
      Metabolism".

PMID- 23127664
TI  - Profiles of quality of life in opiate-dependent individuals after starting
      methadone treatment: a latent class analysis.
AB  - BACKGROUND: This study aimed to identify classes of quality of life (QoL) among
      opiate-dependent individuals five to ten years after starting methadone treatment
      in order to tailor services to the needs of this population. METHODS: A cross
      sectional study of 159 opiate-dependent individuals who started outpatient
      methadone treatment in the region of Ghent, Belgium, between 1997 and 2002. A
      face-to-face structured interview was administered based on the Lancashire
      Quality of Life Profile, the EuropASI, Brief Symptom Inventory and the Verona
      Service Satisfaction Scale for Methadone Treatment. Latent class analysis was
      used to determine patterns of QoL. Analyses of variance and chi-square tests were
      used to test whether class membership was related to socio-demographic, health-
      and drug-related variables. RESULTS: Based on fit criteria, a three-class model
      was selected. Class Low (14.5%), 'opiate-dependent individuals living in marginal
      conditions', is characterised by low QoL scores on all domains. Class
      Intermediate (25.8%), 'stabilized, but socially excluded opiate-dependent
      individuals' shows high scores on the domains 'safety' and 'living situation',
      but low scores on all other QoL domains. Class High (59.7%), 'socially included
      opiate-dependent individuals', is characterised by high QoL scores on all
      domains, except 'finances'. CONCLUSION: The findings of this study illustrate the
      existence of different profiles of QoL among opiate-dependent individuals after
      starting methadone maintenance treatment and demonstrate the need for a
      continuing care approach. Insight into distinct classes of QoL can be used to
      design person-centred support, relevant to an individual's personal life.

PMID- 23127665
TI  - Low Dead-Space Syringes for HIV prevention among people who inject drugs:
      interesting, but a much stronger case is required.

PMID- 23127666
TI  - Saying goodbye to high-dead-space syringes.

PMID- 23127667
TI  - Implementation of low dead-space syringes needs consultation and engagement with
      drug users.

PMID- 23127668
TI  - Is law enforcement of drug-impaired driving cost-efficient? An explorative study
      of a methodology for cost-benefit analysis.
AB  - BACKGROUND: Road users driving under the influence of psychoactive substances may
      be at much higher relative risk (RR) in road traffic than the average driver.
      Legislation banning blood alcohol concentrations above certain threshold levels
      combined with roadside breath-testing of alcohol have been in lieu for decades in
      many countries, but new legislation and testing of drivers for drug use have
      recently been implemented in some countries. METHODS: In this article we present
      a methodology for cost-benefit analysis (CBA) of increased law enforcement of
      roadside drug screening. This is an analysis of the profitability for society,
      where costs of control are weighed against the reduction in injuries expected
      from fewer drugged drivers on the roads. We specify assumptions regarding costs
      and the effect of the specificity of the drug screening device, and quantify a
      deterrence effect related to sensitivity of the device yielding the benefit
      estimates. RESULTS: Three European countries with different current enforcement
      levels were studied, yielding benefit-cost ratios in the approximate range of 0.5
      5 for a tripling of current levels of enforcement, with costs of about 4000 EUR
      per convicted and in the range of 1.5 and 13 million EUR per prevented fatality.
      CONCLUSIONS: The applied methodology for CBA has involved a simplistic
      behavioural response to enforcement increase and control efficiency. Although
      this methodology should be developed further, it is clearly indicated that the
      cost-efficiency of increased law enforcement of drug driving offences is
      dependent on the baseline situation of drug-use in traffic and on the current
      level of enforcement, as well as the RR and prevalence of drugs in road traffic.

PMID- 23127670
TI  - The National Center for Injury Prevention and Control on its 20th Anniversary: a
      safe future and the importance of 20.
AB  - In recognition of NCIPC's role in creating a safer world, we brought together 20
      contributions for this Journal of Safety Research Anniversary Supplement that
      represents the breadth of our work while acknowledging that we cannot truly
      represent the depth of the work over the past two decades. The Center's current
      focal and cross-cutting areas are highlighted in the articles of this Supplement
      and cover a range of activities from violence prevention, unintentional injury,
      to acute care and rehabilitation. The Supplement also contains contributions from
      partners and highlights the resources of the Center.

PMID- 23127671
TI  - The future of injury and violence prevention: where are we going?
AB  - As we are celebrating the 20th anniversary of the National Center for Injury
      Prevention (NCIPC) and Control at the Centers for Disease Control and Prevention
      (CDC), we are looking at the possibilities for progress in the next decade and
      beyond. We face many challenges, but through collaboration, innovation and
      creativity, we can meet the challenges ahead and ensure that the field of injury
      and violence prevention continues to work toward the goal of allowing people to
      live their lives injury and violence free.

PMID- 23127672
TI  - History of Injury and Violence as public health problems and emergence of the
      National Center for Injury Prevention and Control at CDC.
AB  - Injuries and violence are among the oldest health problems facing humans. Only
      within the past 50 years, however, has the problem been addressed with scientific
      rigor using public health methods. The field of injury control began as early as
      1913, but wasn't approached systematically or epidemiologically until the 1940s
      and 1950s. It accelerated rapidly between 1960 and 1985. Coupled with active
      federal and state interest in reducing injuries and violence, this period was
      marked by important medical, scientific, and public health advances. The National
      Center for Injury Prevention and Control (NCIPC) was an outgrowth of this
      progress and in 2012 celebrated its 20th anniversary. NCIPC was created in 1992
      after a series of government reports identified injury as one of the most
      important public health problems facing the nation. Congressional action provided
      the impetus for the creation of NCIPC as the lead federal agency for non
      occupational injury and violence prevention. In subsequent years, NCIPC and its
      partners fostered many advances and built strong capacity. Because of the
      tragically high burden and cost of injuries and violence in the United States and
      around the globe, researchers, practitioners, and decision makers will need to
      redouble prevention efforts in the next 20 years. This article traces the history
      of injury and violence prevention as a public health priority-- including the
      evolution and current structure of the CDC's National Center for Injury
      Prevention and Control.

PMID- 23127673
TI  - Twenty years of scientific progress in injury and violence research and the next
      public health frontier.
AB  - The establishment of the National Center for Injury Prevention and Control (NCIPC
      or Injury Center) in 1992 as part of the Centers for Disease Control and
      Prevention (CDC) firmly established the Injury Center as the lead federal agency
      for non-occupational injury prevention and control (Sleet et al., 2012). Since
      then, it has provided leadership and a strong scientific base for intramural and
      extramural-investigator funded injury research. The Injury Center's scientific
      mission encompasses efforts from primary prevention to treatment and
      rehabilitation. Early CDC efforts were primarily focused on describing the extent
      of the problem, identifying risk and protective factors that affect the extent of
      violence and injury in our society, and gaining visibility for violence and
      injury as a major public health problem. Efforts such as the development of
      injury-based surveillance systems provided population-based surveillance data
      regarding the extent and distribution of fatal and non-fatal injuries, helped to
      identify demographic characteristics for those who were most at risk, and
      identified risk and protective factors that influence that risk. Celebrating the
      Injury Center's 20th anniversary presents an opportunity not only to reflect on
      past accomplishments but also to look ahead at what still needs to be done.

PMID- 23127674
TI  - Top 20 violence and injury practice innovations since 1992.
AB  - This article presents what the authors consider to be among the top 20 practice
      innovations since the inception of the National Center for Injury Prevention and
      Control in 1992. The innovations embody various characteristics of successful
      public health programs and have contributed to declines in violence, motor
      vehicle, residential fire, and other injury rates over the past 20 years. Taken
      together, these innovations have reduced the burden of violence and injury and
      have influenced current practice and practitioners in the United States and
      worldwide.

PMID- 23127675
TI  - Injury and violence prevention policy: celebrating our successes, protecting our
      future.
AB  - Policy strategies for injury and violence prevention influence systems
      development, organizational change, social norms, and individual behavior to
      improve the health and safety of a population. Injury and violence prevention
      professionals should consider how their issues resonate with various audiences,
      including policy makers, the public, and other decision makers. As the cost of
      healthcare continues to rise and greater demands are placed on the healthcare
      system, the use of public health policy becomes increasingly critical to protect
      the public's health and prevent injury and violence and its related morbidities
      and disabilities (Degutis, 2011). This article highlights some impactful policy
      successes from the field, allows us to reflect on the Injury Center's 20th
      anniversary, and describes steps to address injuries and violence into the
      future. The purpose of this paper is to discuss policy as a public health
      strategy and the critical role it plays in injury and violence prevention.

PMID- 23127676
TI  - NCIPC's contribution to global injury and violence prevention: past, present, and
      future.
AB  - Injuries and violence impact millions across the globe each year. For the past 20
      years, the National Center for Injury Prevention and Control (NCIPC) at the
      Centers for Disease Control and Prevention (CDC) has assembled the largest cadre
      of injury and violence prevention experts in the world to reduce the burden of
      injuries and violence domestically and to inform global injury and violence
      prevention efforts. This article focuses on NCIPC's global injury and violence
      prevention work that involves: increasing awareness of the preventability of
      injury and violence, partnerships to promote injury research and best practices;
      establishing standards and guidance for data collection; building capacity
      through training and mentoring; and supporting evidence-based strategies. To
      decrease the global burden, the authors propose priority setting to maximize the
      development and sustainability of financial and human resources for injury and
      violence prevention. IMPACT ON INDUSTRY: The authors call for increased capacity
      and resources for global injury and violence prevention.

PMID- 23127677
TI  - From modest beginnings to a winnable battle: road safety efforts at CDC's Injury
      Center.
AB  - There are now more than 200 million licensed drivers, who drive an average of
      13,000 miles per year on 4 million miles of roads. In 2010 crashes resulted in
      nearly 33,000 deaths and millions of nonfatal injuries. This article describes
      the Injury Center's response to this public health threat from our beginnings as
      a small Center in 1992, current motor vehicle injury prevention priorities, and
      emerging road safety issues that will need attention in the future.

PMID- 23127678
TI  - Prescription drug overdoses: a review.
AB  - PROBLEM: Overdoses involving prescription drugs in the United States have reached
      epidemic proportions over the past 20 years. METHODS: This review categorizes and
      summarizes literature on the topic dating from the first published reports
      through 2011 using a traditional epidemiologic model of host, agent, and
      environment. RESULTS: Host factors include male sex, middle age, non-Hispanic
      white race, low income, and mental health problems. Agent risk factors include
      use of opioid analgesics and benzodiazepines, high prescribed dosage for opioid
      analgesics, multiple prescriptions, and multiple prescribers. Environmental
      factors include rural residence and high community prescribing rates. DISCUSSION:
      The epidemiology of prescription drug overdoses differs from the epidemiology of
      illicit drug overdoses. Incomplete understanding of prescription overdoses
      impedes prevention efforts. SUMMARY: This epidemic demands additional attention
      from injury professionals.

PMID- 23127679
TI  - Preventing violence against children and youth.
AB  - The National Center for Injury Prevention and Control (NCIPC) has a focus on
      preventing interpersonal violence against children and youth. Prevention of
      violence against children and youth involves fostering healthy relationships and
      building healthy environments in which young people can flourish. We review
      NCIPC's work over the past 20 years that has contributed to this goal by
      highlighting surveillance systems that identify the magnitude of violence,
      etiological research that identifies risk and protective factors that are
      associated with violence, evaluation research that has expanded the evidence base
      of what works to prevent violence, and comprehensive, broad-based programs that
      engage and empower communities to prevent violence. NCIPC's work demonstrates
      that violence is preventable and the Center is working to move the promise of
      effective prevention into practice. These efforts all work toward protecting the
      health and well-being of children and youth and set the stage for NCIPC's future
      work.

PMID- 23127680
TI  - Trends in Traumatic Brain Injury in the U.S. and the public health response: 1995
      2009.
AB  - PROBLEM: Traumatic Brain Injury (TBI) is a public health problem in the United
      States. In 2009, approximately 2.4 million [corrected] patients with a TBI listed
      as primary or secondary diagnosis were hospitalized and discharged alive
      (N=300,667) or were treated and released from emergency departments (EDs;
      N=2,077,350), outpatient departments (ODs; N=83,857), and office-based physicians
      (OB-P; N=1,079,338). In addition, 52,695 died with one or more TBI-related
      diagnoses. METHODS: Federal TBI-related laws that have guided CDC since 1996 were
      reviewed. Trends in TBI were obtained by analyzing data from nationally
      representative surveys conducted by the National Center for Health Statistics
      (NCHS). FINDINGS: CDC has developed and is implementing a strategy to reduce the
      burden of TBI in the United States. Currently, 20 states have TBI surveillance
      and prevention systems. From 1995-2009, the TBI rates per 100,000 population
      increased in EDs (434.1 vs. 686.0) and OB-Ps (234.6 vs. 352.3); and decreased in
      ODs (42.6 vs. 28.1) and in TBI-related deaths (19.9 vs. 16.6). TBI
      Hospitalizations decreased from 95.5 in 1995 to 77.9 in 2000 and increased to
      95.7 in 2009. CONCLUSIONS: The rates of TBI have increased since 1995 for ED and
      PO visits. To reduce of the burden and mitigate the impact of TBI in the United
      States, an improved state- and territory-specific TBI surveillance system that
      accurately measures burden and includes information on the acute and long-term
      outcomes of TBI is needed.

PMID- 23127681
TI  - National football league.

PMID- 23127682
TI  - Young athletes protected by concussion law.

PMID- 23127683
TI  - Laying tracks of hope: Kentucky's involvement in the EMPOWER program.

PMID- 23127684
TI  - CDC Foundation.

PMID- 23127685
TI  - The next 20 years--challenges and opportunities for injury and violence
      prevention.

PMID- 23127686
TI  - Reflections on NCIPC's 20 Years of Injury
      Control.......Then......Now......Imagine.

PMID- 23127689
TI  - Effect of body mass index, physical activity, depression, and educational
      attainment on high-sensitivity C-reactive protein in patients with atrial
      fibrillation.
AB  - Atherosclerosis development is a complex process, with inflammation, indicated by
      elevated high-sensitivity C-reactive protein (hs-CRP), as a potential mediator.
      Obesity, physical activity, and depression have all been reported to affect hs
      CRP. However, these factors are interconnected, and their relative individual
      importance remains unclear. From a separate prospective cohort study, 289
      patients were selected for the present substudy. We assessed the relation of a
      variety of potential predictors and hs-CRP. Obesity, physical activity, and
      depression, in addition to several other potential factors, were analyzed in
      bivariate and multivariate linear regression models, adjusting for potential
      confounders. In unadjusted analyses, mild-to-moderate and severe depression were
      associated with increased hs-CRP compared to no or minimal depression. Vigorous
      physical activity was associated with decreased hs-CRP compared to no physical
      activity. All classes of obesity were associated with increased hs-CRP. In
      addition, attaining a college or graduate degree was associated with decreased hs
      CRP compared to high school or less educational attainment. On multivariate
      analysis, depression was no longer associated with increased hs-CRP. Physical
      activity remained associated with decreased hs-CRP but only at vigorous levels.
      Educational attainment also remained associated but only at the collegiate or
      professional education level. Ultimately, obesity remained the greatest absolute
      predictor of elevated hs-CRP. In conclusion, in analyses of multiple factors
      potentially predictive of elevated hs-CRP in a large population of patients with
      subclinical coronary heart disease, we found the most important predictor to be
      obesity.

PMID- 23127690
TI  - Relation of circulating liver transaminase concentrations to risk of new-onset
      atrial fibrillation.
AB  - Heart failure, a strong risk factor for atrial fibrillation (AF), is often
      accompanied by elevated liver transaminases. The aim of this study was to test
      the hypothesis that elevated transaminases are associated with the risk for
      incident AF in the community. A total of 3,744 participants (mean age 65 +/- 10
      years, 56.8% women) from the Framingham Heart Study Original and Offspring
      cohorts, free of clinical heart failure, were studied. Cox proportional-hazards
      models adjusted for standard AF risk factors (age, gender, body mass index,
      systolic blood pressure, electrocardiographic PR interval, antihypertensive
      treatment, smoking, diabetes, valvular heart disease, and alcohol consumption)
      were examined to investigate associations between baseline serum transaminase
      levels (alanine transaminase and aspartate transaminase) and the incidence of AF
      over up to 10 years (29,099 person-years) of follow-up. During follow-up, 383
      subjects developed AF. The 2 transaminases were significantly associated with
      greater risk for incident AF (hazard ratio expressed per SD of natural
      logarithmically transformed biomarker: alanine transaminase hazard ratio 1.19,
      95% confidence interval 1.07 to 1.32, p = 0.002; aspartate transaminase hazard
      ratio 1.12, 95% confidence interval 1.01 to 1.24, p = 0.03). The associations
      between transaminases and AF remained consistent after the exclusion of
      participants with moderate to severe alcohol consumption. However, when added to
      known risk factors for AF, alanine transaminase and aspartate transaminase only
      subtly improved the prediction of AF. In conclusion, elevated transaminase
      concentrations are associated with increased AF incidence. The mechanisms by
      which higher mean transaminase concentrations are associated with incident AF
      remain to be determined.

PMID- 23127691
TI  - Foot-and-mouth disease virus strains and examination of exposure factors
      associated with seropositivity of cattle herds in Nigeria during 2007-2009.
AB  - New outbreaks of foot-and-mouth disease (FMD) occurred in cattle herds in Nigeria
      during 2007-2009. The objectives of the study reported here were: (i) to identify
      current FMD virus strains circulating in cattle herds and (ii) to identify
      exposure factors associated with a seropositive diagnosis of FMD in cattle herds.
      This study provides evidence that FMD virus serotypes O, A and SAT-2 were co
      circulating in cattle herds in Nigeria during 2007-2009. Cattle herds in a
      neighborhood affected with FMD had higher odds of being classified as
      seropositive to FMD, compared to herds that were in a neighborhood not affected
      with FMD (OR=16.27; 95% CI=3.61, 18.74; P<0.01). Cattle herds that share water
      points along the trek routes with other cattle herds had higher odds of being
      classified as seropositive to FMD (adjusted OR=4.15; 95% CI=0.92, 18.74; P<0.06).
      Results from this study can be used by veterinary services in Nigeria and
      neighboring countries to evaluate current or future FMD control and eradication
      programs.

PMID- 23127692
TI  - Household-level risk factors for Newcastle disease seropositivity and incidence
      of Newcastle disease virus exposure in backyard chicken flocks in Eastern Shewa
      zone, Ethiopia.
AB  - A cross-sectional study with repeated sampling was conducted to investigate
      potential risk factors for Newcastle disease (ND) seropositivity and for
      incidence of ND virus (NDV) exposure in household flocks of backyard chickens in
      Eastern Shewa zone, Ethiopia. Data were collected from 260 randomly selected
      households in 52 villages in Adami Tulu Jido Kombolcha and Ada'a woredas
      (districts) using a structured questionnaire, and serum samples from chickens
      were tested for NDV antibodies using a blocking enzyme-linked immunosorbent assay
      (ELISA). Sampling took place during September 2009 and the same households were
      again sampled in May 2010. Household-level seroprevalence and incidence of NDV
      exposure were estimated in various ways using serological results from the two
      samplings, flock dynamics, and farmers' reports of ND in their flocks. The risk
      factors were assessed using multivariable mixed-effects logistic regression
      models. Household-level seroprevalence at the two sampling times was 17.4% and
      27.4%, respectively, and the estimated incidence of household-level NDV exposure
      during the intervening period ranged between 19.7% and 25.5%. At the first
      sampling, reduced frequency of cleaning of poultry waste was associated with
      increased odds of seropositivity (OR=4.78; 95% CI: 1.42, 16.11; P=0.01) while
      hatching at home vs. other sources (buying in replacement birds, receiving as
      gift or buying fertile eggs) was associated with lower odds of seropositivity,
      both at the first sampling (OR=0.30; 95% CI: 0.11, 0.82; P=0.02) and the second
      sampling (OR=0.23; 95% CI: 0.10, 0.52; P<0.001). The risk of NDV exposure was
      shown to be higher with larger flock size at the beginning of the observation
      period (OR=3.6; 95% CI: 1.25, 10.39; P=0.02). Using an open water source (pond or
      river) for poultry compared to closed sources (tap or borehole) was associated
      with increased risk of NDV exposure (OR=3.14; 95% CI: 1.12, 8.8; P=0.03). The use
      of a grain supplement (OR=0.14; 95% CI: 0.03, 0.69; P=0.03) and hatching at home
      for flock replacement (OR=0.23; 95% CI: 0.10, 0.52; P=0.005) were associated with
      a lower risk of NDV exposure. Newcastle disease seroprevalence and incidence of
      NDV exposure were more heterogeneous between villages than between kebeles
      (aggregations of villages) and woredas in the study area. Further investigation
      of village-level risk factors would likely improve our understanding of ND
      epidemiology in backyard chickens.

PMID- 23127693
TI  - Con: etomidate--the ideal induction agent for a cardiac anesthetic?

PMID- 23127694
TI  - Pro: etomidate is the ideal induction agent for a cardiac anesthetic.

PMID- 23127695
TI  - Anesthesiologists and transesophageal echocardiography: echocardiographers or
      echocardiologists?

PMID- 23127696
TI  - Impact of online transesophageal echocardiographic simulation on learning to
      navigate the 20 standard views.
AB  - OBJECTIVE: To overcome a challenge in transesophageal echocardiographic (TEE)
      training, an online virtual TEE simulation was developed that allows the user to
      navigate among the 20 standard views. The TEE probe position and ultrasound plane
      movements on a 3-dimensional heart model were displayed with the corresponding
      TEE video recording as the probe was moved among the views. DESIGN: This study
      evaluated the educational benefit of the virtual TEE application using a
      pretest/post-test design. SETTING: Single academic teaching hospital.
      PARTICIPANTS: Ten postgraduate physician volunteers who were novice
      echocardiographers. INTERVENTIONS: In a controlled environment, 10 study subjects
      completed a 20 multiple-choice question pretest, used the simulation for 1 hour,
      and then completed a 20 multiple-choice question post-test. Percentages of
      correct answers for each test were recorded for each subject. MEASUREMENTS AND
      MAIN RESULTS: The hypothesis that the median improvement in the number of
      questions correctly answered was different from 0 was tested with a related
      samples Wilcoxon signed-rank test. A p value <0.05 was considered significant. A
      1-hour exposure to the virtual TEE simulation produced a significant improvement
      (p = 0.005) in the post-test score (median 80%) compared with the pretest score
      (median 20%). CONCLUSIONS: Using the virtual TEE simulation for 1 hour
      significantly improves the trainees' knowledge of navigation among the 20
      standard TEE views. This application freely is available on the Internet and will
      be a useful adjunct to TEE training programs.

PMID- 23127697
TI  - Major surgery, hemodynamic instability, and a left atrial appendage clot: what to
      do?

PMID- 23127698
TI  - Conjunctival modifications induced by medical and surgical therapies in patients
      with glaucoma.
AB  - Lowering intra-ocular pressure, either medically or surgically, is the proven
      strategy to control glaucoma, though profound changes to the ocular surface and
      conjunctiva are caused. Toxicity and allergy initiated by medical therapy induce
      modifications, which progressively worsen with the length of treatment and number
      of drugs. Conjunctival changes lead to symptoms of ocular surface disease,
      reduced quality of life, reduced therapeutic compliance and increased risk of
      surgical failure. Surgery modifies conjunctiva by inducing bleb formation in
      fistulizing techniques, and by activating secondary aqueous humour outflow
      pathways, such as trans-scleral routes, in both filtration and bleb-less
      approaches. The use of unpreserved medications, limitation of intra-operative
      conjunctival damage and development of bleb-less surgery are advisable.

PMID- 23127699
TI  - Effect of native microflora, waiting period, and storage temperature on Listeria
      monocytogenes serovars transferred from cantaloupe rind to fresh-cut pieces
      during preparation.
AB  - The most recent outbreak of listeriosis linked to consumption of fresh-cut
      cantaloupes indicates the need to investigate the behavior of Listeria
      monocytogenes in the presence of native microflora of cantaloupe pieces during
      storage. Whole cantaloupes were inoculated with L.  monocytogenes (10(8)-CFU/ml
      suspension) for 10 min and air dried in a biosafety cabinet for 1 h and then
      treated (unwashed, water washed, and 2.5% hydrogen peroxide washed). Fresh-cut
      pieces (~3 cm) prepared from these melons were left at 5 and 10 degrees C for 72
      h and room temperature  (20 degrees C) for 48 h. Some fresh-cut pieces were left
      at 20 degrees C for 2 and 4 h and then refrigerated at 5 degrees C. Microbial
      populations of fresh-cut pieces were determined by the plate count method or
      enrichment method immediately after preparation. Aerobic mesophilic bacteria,
      yeast and mold  of whole melon, and inoculated populations of L. monocytogenes on
      cantaloupe rind surfaces averaged 6.4, 3.3, and 4.6 log CFU/cm(2), respectively.
      Only H(2)O(2) (2.5%) treatment reduced the aerobic mesophilic bacteria, yeast and
      mold, and L. monocytogenes  populations to 3.8, 0.9, and 1.8 log CFU/cm(2),
      respectively. The populations of L. monocytogenes transferred from melon rinds to
      fresh-cut pieces were below detection but were present by enrichment. Increased
      storage temperatures enhanced the lag phases and growth of L.  monocytogenes. The
      results of this study confirmed the need to store fresh-cut cantaloupes at 5
      degrees C immediately after preparation to enhance the microbial safety of the
      fruit.

PMID- 23127700
TI  - Transfer of Escherichia coli O157:H7 from equipment surfaces to fresh-cut leafy
      greens during processing in a model pilot-plant production line with sanitizer
      free water.
AB  - Escherichia coli O157:H7 contamination of fresh-cut leafy greens has become a
      public health concern as a result of several large outbreaks. The goal of this
      study was to generate baseline data for E. coli O157:H7 transfer from product
      inoculated equipment surfaces to uninoculated  lettuce during pilot-scale
      processing without a sanitizer. Uninoculated cored heads of iceberg and romaine
      lettuce (22.7 kg) were processed using a commercial shredder, step conveyor, 3.3
      m flume tank with sanitizer-free tap water, shaker table, and centrifugal dryer,
      followed by 22.7 kg of  product that had been dip inoculated to contain ~10(6),
      10(4), or 10(2) CFU/g of a four-strain avirulent, green fluorescent protein
      labeled, ampicillin-resistant E. coli O157:H7 cocktail. After draining the flume
      tank and refilling the holding tank  with tap water, 90.8 kg of uninoculated
      product was similarly processed and collected in ~5-kg aliquots. After
      processing, 42 equipment surface samples and 46 iceberg or 36 romaine lettuce
      samples (25 g each) from the collection baskets were quantitatively examined for
      E. coli O157:H7  by direct plating or membrane filtration using tryptic soy agar
      containing 0.6% yeast extract and 100 ppm of ampicillin. Initially, the greatest
      E. coli O157:H7 transfer was seen from inoculated lettuce to the shredder and
      conveyor belt, with all equipment surface populations decreasing  90 to 99% after
      processing 90.8 kg of uncontaminated product. After processing lettuce containing
      10(6) or 10(4) E. coli O157:H7 CFU/g followed by uninoculated lettuce, E. coli
      O157:H7 was quantifiable throughout the entire 90.8 kg of product. At an
      inoculation  level of 10(2) CFU/g, E. coli O157:H7 was consistently detected in
      the first 21.2 kg of previously uninoculated lettuce at 2 to 3 log CFU/100 g and
      transferred to 78 kg of product. These baseline E. coli O157:H7 transfer results
      will help determine the degree of sanitizer  efficacy required to better ensure
      the safety of fresh-cut leafy greens.

PMID- 23127701
TI  - Evaluation of sanitizers for inactivating Salmonella on in-shell pecans and pecan
      nutmeats.
AB  - Chlorine, organic acids, and water extracts of inedible pecan components were
      tested for effectiveness in killing Salmonella on pecans. In-shell pecans and
      nutmeats (U.S. Department of Agriculture medium pieces) were immersion inoculated
      with a mixture of five Salmonella  serotypes, dried to 3.7% moisture, and stored
      at 4 degrees C for 3 to 6 weeks. In-shell nuts were immersed in chlorinated water
      (200, 400, and 1,000 MUg/ml), lactic acid (0.5, 1, and 2%), and levulinic acid
      (0.5, 1, and 2%) with and without 0.05% sodium dodecyl sulfate (SDS), and a mixed
      peroxyacid  sanitizer (Tsunami 200, 40 MUg/ml) for up to 20 min at 21 degrees C.
      The rate of reduction of free chlorine in conditioning water decreased as the
      ratio of in-shell nuts/water was increased. The rate of reduction was more rapid
      when nuts were not precleaned before treatment. The initial population  of
      Salmonella on in-shell nuts (5.9 to 6.3 log CFU/g) was reduced by 2.8 log CFU/g
      after treating with chlorinated water (1,000 MUg/ml). Treatment with 2% lactic
      acid plus SDS or 2% levulinic acid plus SDS reduced the pathogen by 3.7 and 3.4
      log CFU/g, respectively. Lactic and levulinic  acids (2%) without SDS were less
      effective (3.3- and 2.1-log CFU/g reductions, respectively) than acids with SDS.
      Treatment with Tsunami 200 resulted in a 2.4-log CFU/g reduction. In-shell nuts
      and nutmeats were immersed in water extracts of ground pecan shucks (hulls),
      shells, a mixture of  shells and pith, and pith. The general order of lethality
      of extracts to Salmonella was shuck < shell-pith <= shell <= pith < chlorine (400
      MUg/ml) and shuck < shell <= pith = shell-pith < chlorine (400 MUg/ml). Results
      emphasize the importance of removing soil  and dust on in-shell pecans before
      conditioning in chlorinated water and the need for sanitizers with increased
      effectiveness in killing Salmonella on pecans.

PMID- 23127702
TI  - Influence of primer sequences and DNA extraction method on detection of non-O157
      Shiga toxin-producing Escherichia coli in ground beef by real-time PCR targeting
      the eae, stx, and serogroup-specific genes.
AB  - Non-O157 Shiga toxin-producing Escherichia coli (STEC) infections, particularly
      those caused by the "big six" or "top six" non-O157 serogroups (O26, O45, O103,
      O111, O121, and O145) can result in severe illness and complications. Because of
      their  significant public health impact and the notable prevalence of STEC in
      cattle, methods for detection of the big six non-O157 STEC in ground beef have
      been established. Currently, the U.S. Department of Agriculture, Food Safety and
      Inspection Service detection methods for screening beef samples  for non-O157
      STEC target the stx(1), stx(2), and eae virulence genes, with the 16S rRNA gene
      as an internal control, in a real-time PCR multiplex assay. Further, the
      serogroup is determined by PCR targeting genes in the E. coli O-antigen gene
      clusters  of the big six non-O157 serogroups. The method that we previously
      reported was improved so that additional stx variants, stx(1d), stx(2e), and
      stx(2g), are detected. Additionally, alignments of the primers targeting the eae
      gene  were used to improve the detection assay so that eae subtypes that could
      potentially be of clinical significance would also be detected. Therefore,
      evaluation of alternative real-time PCR assay primers and probes for the stx and
      eae reactions was carried out in order to  increase the stx and eae subtypes
      detected. Furthermore, a Tris-EDTA DNA extraction method was compared with a
      previously used procedure that was based on a commercially available reagent. The
      Tris-EDTA DNA extraction method significantly decreased the cycle threshold
      values  for the stx assay (P < 0.0001) and eae assay (P < 0.0001), thereby
      increasing the ability to detect the targets. The use of different stx primers
      and probes increased the subtypes detected to include stx(1d), stx(2e),  and
      stx(2g), and sequence data showed that modification of the eae primer should
      allow the known eae subtypes to be detected.

PMID- 23127703
TI  - Efficient separation and sensitive detection of Listeria monocytogenes using an
      impedance immunosensor based on magnetic nanoparticles, a microfluidic chip, and
      an interdigitated microelectrode.
AB  - Listeria monocytogenes continues to be a major foodborne pathogen that causes
      food poisoning, and sometimes death, among immunosuppressed people and abortion
      among pregnant women. In this study, magnetic nanoparticles with a diameter of 30
      nm were functionalized with anti-L.  monocytogenes antibodies via biotin
      streptavidin bonds to become immunomagnetic nanoparticles (IMNPs) to capture L.
      monocytogenes in a sample during a 2-h immunoreaction. A magnetic separator was
      used to collect and hold the IMNPs-L. monocytogenes complex while the 
      supernatants were removed. After the washing step, the nanoparticle-L.
      monocytogenes complex was separated from the sample and injected into a
      microfluidic chip. The impedance change caused by L. monocytogenes was measured
      by an impedance analyzer through the interdigitated  microelectrode in the
      microfluidic chip. For L. monocytogenes in phosphate-buffered saline solution, up
      to 75% of the cells in the sample could be separated, and as few as three to five
      cells in the microfluidic chip could be detected, which is equivalent to 10(3)
      CFU/ml of  cells in the original sample. The detection of L. monocytogenes was
      not interfered with by other major foodborne bacteria, including E. coli O157:H7,
      E. coli K-12, L. innocua, Salmonella Typhimurium, and Staphylococcus aureus. A
      linear correlation (R(2)  = 0.86) was found between the impedance change and the
      number of L. monocytogenes in a range of 10(3) to 10(7) CFU/ml. Equivalent
      circuit analysis indicated that the impedance change was mainly due to the
      decrease in medium resistance when the IMNPs-L. monocytogenes  complexes existed
      in mannitol solution. Finally, the immunosensor was evaluated with food sample
      tests; the results showed that, without preenrichment and labeling, 10(4) and
      10(5) CFU/ml L. monocytogenes in lettuce, milk, and ground beef samples could be
      detected  in 3 h.

PMID- 23127704
TI  - Efficacy of chemical interventions against Escherichia coli O157:H7 and multidrug
      resistant and antibiotic-susceptible Salmonella on inoculated beef trimmings.
AB  - Studies were conducted to compare the decontamination efficacy of six chemical
      treatments against Escherichia coli O157:H7 and multidrug-resistant and
      antibiotic-susceptible Salmonella inoculated on beef trimmings. The inocula,
      comprising four-strain mixtures of rifampin-resistant  E. coli O157:H7 and
      antibiotic-susceptible or multidrug-resistant (MDR and/or MDR-AmpC) Salmonella
      Newport and Salmonella Typhimurium, were inoculated (3 log CFU/cm(2)) separately
      onto samples (10 by 5 by 1 cm) derived from beef chuck rolls. Samples were left 
      untreated (control), were immersed for 30 s in acidified sodium chlorite (0.1%,
      pH 2.5), peroxyacetic acid (0.02%, pH 3.8), sodium metasilicate (4%, pH 12.6),
      Bromitize Plus (0.0225% active bromine, pH 6.6), or AFTEC 3000 (pH 1.2), or were
      immersed for 5 s in SYNTRx 3300 (pH 1.0). Levels of  surviving Salmonella on
      treated trimmings were not influenced by serotype or antibiotic resistance
      phenotype and were generally similar (P >= 0.05) or lower (P < 0.05) than levels
      of surviving E. coli O157:H7 regardless of antimicrobial treatment. Overall, 
      depending on chemical treatment (reductions within each chemical treatment were
      similar among all tested inocula), initial counts of E. coli O157:H7 (2.7 to 3.1
      log CFU/cm(2)) were reduced (P < 0.05) by 0.2 to 1.4 log CFU/cm(2). Similarly,
      initial counts  of the tested Salmonella inocula (2.8 to 3.3 log CFU/cm(2)) were
      reduced (P < 0.05) by 0.4 to 1.4 (Salmonella Newport, antibiotic susceptible),
      0.3 to 1.4 (Salmonella Newport, MDR-AmpC), 0.2 to 1.5 (Salmonella Typhimurium,
      antibiotic susceptible),  0.4 to 1.3 (Salmonella Typhimurium, MDR), and 0.4 to
      1.5 (Salmonella Typhimurium, MDR-AmpC) log CFU/cm(2), depending on antimicrobial
      treatment. Reductions obtained with sodium metasilicate were 1.3 to 1.5 log
      CFU/cm(2), regardless of inoculum, and reductions  obtained with the five
      remaining antimicrobial treatments were 0.2 to 0.7 log CFU/cm(2) (depending on
      treatment). Findings of this study should be useful to regulatory authorities and
      the meat industry as they consider Salmonella contamination on beef trimmings.

PMID- 23127705
TI  - Validation comparing the effectiveness of a lactic acid dip with a lactic acid
      spray for reducing Escherichia coli O157:H7, Salmonella, and non-O157 Shiga
      toxigenic Escherichia coli on beef trim and ground beef.
AB  - The objective of this research was to compare the effectiveness of two
      application methods (dip versus spray) of 4.4% lactic acid for reducing pathogens
      on inoculated beef trim and in ground beef. Beef trim inoculated with cocktail
      mixtures of E. coli O157:H7, non-O157 Shiga  toxigenic E. coli (STEC), or
      Salmonella (10(5) to 10(6) CFU/g) at separate times was subjected to five
      treatments: lactic acid spray (LS), lactic acid dip (LD), water spray (WS), water
      dip (WD), and untreated control (CTL). Intervention effectiveness for pathogen 
      reduction was measured at 1 and 20 h after treatment on beef trim. Trim was then
      ground and intervention effectiveness was measured 1 h, 24 h, 72 h, and 7 days
      after grinding. The LD treatment reduced all pathogens significantly (P < 0.05);
      E. coli O157:H7 was reduced by 0.91  to 1.41 log CFU/g on beef trim and ground
      beef, non-O157 STEC by 0.48 to 0.82 log CFU/g, and Salmonella by 0.51 to 0.81 log
      CFU/g. No other treatment significantly reduced any pathogen, although the WD
      treatment noticeably reduced (P > 0.05) both E. coli O157:H7 and  non-O157 STEC
      populations compared with the CTL. The LS treatment reduced E. coli O157:H7 and
      Salmonella by up to 0.5 log CFU/g on beef trim, but these reduced counts did not
      significantly differ (P > 0.05) from the CTL counts. Overall, the LD treatment
      was most effective  for reducing all pathogens and is the best of these options
      for improving the safety of beef trim and subsequently produced ground beef.

PMID- 23127706
TI  - Effect of organic acids on Salmonella colonization and shedding in weaned piglets
      in a seeder model.
AB  - Piglets (n = 128) weaned at 21 days of age were used in a 35-day seeder model to
      evaluate the effects of dietary additives differing in active ingredients,
      chemical, and physical formulation, and dose on Salmonella colonization and
      shedding and intestinal microbial populations.  Treatments were a negative
      control (basal diet), the positive control (challenged, basal diet), and six
      treatments similar to the positive control but supplemented with the following
      active ingredients (dose excluding essential oils or natural extracts):
      triglycerides with butyric acid (1.30  g kg(-1)); formic and citric acids and
      essential oils (2.44 g kg(-1)); coated formic, coated sorbic, and benzoic acids
      (2.70 g kg(-1)); salts of formic, sorbic, acetic, and propionic acids, their free
      acids, and natural extracts (2.92 g kg(-1));  triglycerides with caproic and
      caprylic acids and coated oregano oil (1.80 g kg(-1)); and caproic, caprylic,
      lauric, and lactic acids (1.91 g kg(-1)). On day 6, half the piglets (seeder
      pigs) in each group were orally challenged with a Salmonella Typhimurium 
      nalidixic acid-resistant strain (4 * 10(9) and 1.2 * 10(9) log CFU per pig in
      replicate experiments 1 and 2, respectively). Two days later, they were
      transferred to pens with an equal number of contact pigs. Salmonella shedding was
      determined 2 days  after challenge exposure and then on a weekly basis. On day 34
      or 35, piglets were euthanized to sample tonsils, ileocecal lymph nodes, and
      ileal and cecal digesta contents. The two additives, both containing short-chain
      fatty acids and one of them also containing benzoic acid and the other  one also
      containing essential oils, and supplemented at more than 2.70 g kg(-1), showed
      evidence of reducing Salmonella fecal shedding and numbers of coliforms and
      Salmonella in cecal digesta. However, colonization of tonsils and ileocecal lymph
      nodes by Salmonella  was not affected. Supplementing butyric acid and medium
      chain fatty acids at the applied dose failed to inhibit Salmonella contamination
      in the current experimental setup.

PMID- 23127707
TI  - Human norovirus surrogate reduction in milk and juice blends by high pressure
      homogenization.
AB  - Novel processing technologies such as high pressure homogenization (HPH) for the
      inactivation of foodborne viruses in fluids that retain nutritional attributes
      are in high demand. The objectives of this research were (i) to determine the
      effects of HPH alone or with an emulsifier (lecithin)  on human norovirus
      surrogates-murine norovirus (MNV-1) and feline calicivirus (FCV-F9)-in skim milk
      and orange juice, and (ii) to determine HPH effects on FCV-F9 and MNV-1 in orange
      and pomegranate juice blends. Experiments were conducted in duplicate at 0, 100,
      200, 250, and 300  MPa for <2 s and plaque was assayed in duplicate. In milk, FCV
      F9 was reduced by >=4 and ~1.3 log PFU/ml at 300 and 250 MPa, respectively, and
      >=4- and ~1-log PFU/ml reductions were obtained in orange juice at 300 and 250
      MPa, respectively. In orange juice or milk combined with  lecithin, FCV-F9 was
      reduced to nondetectable levels at 300 MPa, and by 1.77 and 0.78 log PFU/ml at
      250 MPa. MNV-1 in milk was reduced by ~1.3 log PFU/ml only at 300 MPa, and by
      ~0.8 and ~0.4 log PFU/ml in orange juice at 300 and 250 MPa, respectively. MNV-1
      in milk or orange juice  containing lecithin at 300 MPa showed 1.32- and 2.5-log
      PFU/ml reductions, respectively. In the pomegranate-orange juice blend, FCV-F9
      was completely reduced, and MNV-1 was reduced by 1.04 and 1.78 log PFU/ml at 250
      and 300 MPa, respectively. These results show that HPH has potential for
      commercial  use to inactivate foodborne virus surrogates in juices.

PMID- 23127708
TI  - Occurrence of aflatoxins in herbal medicine distributed in South Korea.
AB  - The objective of this study was to investigate the occurrence of aflatoxins in
      herbal medicines distributed in South Korea. A total of 700 herbal medicine
      samples (10 samples each for 70 types of herbal medicine) were analyzed by an
      enzyme-linked immunosorbent assay (ELISA) for aflatoxin  B(1) (AFB(1)), and
      levels of total aflatoxins were quantified and confirmed by liquid chromatography
      combined with tandem mass spectrometry (LC-MS/MS). The levels of recovery of the
      methods were 84.30 to 102.68% (ELISA for AFB(1)) and 72.17 to 90.92% (LC-MS/MS
      for  total aflatoxins). Fifty-eight (8.29%) of 700 samples were AFB(1) positive
      by ELISA, and 17 (2.43%) of them were finally confirmed as positive for total
      aflatoxins by LC-MS/MS. Total aflatoxin levels in the herbal medicines were from
      4.51 to 108.42 MUg/kg. Among the 17 samples,  the AFB(1) content of 6 samples
      (11.95 to 73.27 MUg/kg) and the total aflatoxin content of 10 (12.12 to 108.42
      MUg/kg) samples exceeded the legal limits set by the Korea Food and Drug
      Administration for AFB(1) (10 MUg/kg) and by the European Commission for total
      aflatoxins  (10 MUg/kg), respectively. These results demonstrate the risk to
      consumers of herbal medicine contamination by aflatoxins and encourage further
      studies to investigate the transfer rate of mycotoxins to decoction, which is the
      final product for consumption.

PMID- 23127709
TI  - First detection and seasonal variation of lipophilic toxins okadaic acid,
      dinophysistoxin-1, and yessotoxin in Korean gastropods.
AB  - Okadaic acid (OA), dinophysistoxin-1 (DTX1), pectenotoxin-2, and yessotoxin (YTX)
      are classes of lipophilic toxins found in marine animals. OA and DTX1
      accumulation causes diarrhetic shellfish poisoning, a worldwide public health
      problem. Diarrhetic shellfish poisoning has not previously  been reported in
      gastropods, which are widely consumed in Korea. Seasonal variation in marine
      lipophilic toxins in gastropods was investigated using liquid chromatography
      tandem mass spectrometry. Eighty specimens of Neptunea cumingii, 65 specimens of
      Rapana venosa, and  95 specimens of Batillus cornutus were collected at the
      Tongyeong fish market on the southern coast of Korea between May 2009 and
      December 2010. OA, DTX1, and YTX were detected in meat and digestive glands in
      all gastropod species studied. Pectenotoxin-2 was not found in any sample 
      tested. Lipophilic toxins were detected in the digestive glands of gastropods; no
      lipophilic toxin was detected in the salivary glands of the carnivorous
      gastropods, N. cumingii and R. venosa. The highest concentrations of OA (21.5
      ng/g) and DTX1 (8.4 ng/g) were detected in the  digestive glands of R. venosa,
      and the maximum concentration of YTX (13.7 ng/g) was found in the digestive
      glands of N. cumingii. The maximum toxicities in gastropod tissues were lower
      than the European standard for acceptable levels. The concentrations of
      lipophilic toxins in  carnivorous gastropods showed a high degree of seasonal
      variation; lipophilic toxins in carnivorous gastropods were found predominantly
      in spring and summer. This is the first report of the occurrence of lipophilic
      toxins in Korean gastropods.

PMID- 23127710
TI  - Health department inspection criteria more likely to be associated with outbreak
      restaurants in Minnesota.
AB  - Millions of routine restaurant inspections are performed each year in the United
      States, and the Centers for Disease Control and Prevention has reported that a
      majority of foodborne illness outbreaks occur in restaurant settings. In an
      attempt to relate the data collected during inspections  in Minnesota to illness
      likelihood, data from routine inspections conducted at outbreak restaurants were
      compared with data from routine inspections conducted at nonoutbreak restaurants.
      The goal was to identify differences in recorded violations. Significantly more
      violations were recorded  at restaurants that had outbreaks. The majority of
      these violations were related to contamination in the facility and environment
      and to food handling procedures. Relative risks also were calculated for
      violations significantly more likely to occur at locations that had outbreaks of
      norovirus  infection, Clostridium perfringens infection or toxin-type illness,
      and Salmonella infection. These three pathogens are estimated to cause the
      majority of foodborne illnesses in the United States. Meta-analysis of composited
      data for the three pathogens revealed 11 violations  significantly more likely
      (alpha < 0.05) to be identified during routine inspections at outbreak
      restaurants than during inspections at nonoutbreak restaurants. Application of
      this information permits assessment of health department inspection data in a
      consistent fashion. This approach  can help identify criteria more likely to be
      associated with outbreak locations and allow operators to focus on interventions
      that will have the most significant impact in higher risk establishments.

PMID- 23127711
TI  - Using a theoretical predictive tool for the analysis of recent health department
      inspections at outbreak restaurants and relation of this information to foodborne
      illness likelihood.
AB  - Because U.S. restaurants are inspected at least annually against criteria in the
      U.S. Food and Drug Administration Model Food Code, large amounts of data are
      generated and should be systematically reviewed. The purpose of this study was to
      determine the relationships among the data  obtained through health department
      inspections, the contributing factors to foodborne illness identified by the
      Centers for Disease Control and Prevention, and the risks of outbreaks of
      norovirus, Salmonella, and Clostridium perfringens infection associated with a
      specific restaurant.  These agents were chosen for the analysis because they
      cause the majority of foodborne illnesses. A theoretical predictive assessment
      tool was built that extracts data from routine health department inspection
      reports for specific restaurants to establish a risk profile for each restaurant 
      and identify the likelihood of a norovirus, Salmonella, or C. perfringens
      outbreak at that restaurant. The tool was used to examine inspection reports from
      restaurants known to have had confirmed norovirus, Salmonella, and C. perfringens
      outbreaks. Although evaluation  of an extensive data set revealed lack of an
      overall association between outbreak inspection scores and routine inspection
      scores obtained at outbreak restaurant locations, certain specific violations
      were significantly more likely to be recorded. Significant differences in types
      of violations  recorded during outbreak and routine inspections were determined.
      When risks based on violation type can be identified, targeted actions may be
      able to be prioritized and implemented to help decrease illnesses.

PMID- 23127712
TI  - Isolation of Shiga toxin-producing Escherichia coli from fresh produce using STEC
      heart infusion washed blood agar with mitomycin-C.
AB  - The ability to detect and isolate Shiga toxin-producing Escherichia coli (STEC)
      remains a major challenge for food microbiologists. Although methods based on
      nucleic acids and antibodies have improved detection of STECs in foods, isolation
      of these bacteria remains arduous.  STEC isolation is necessary for matching
      food, environmental, and clinical isolates during outbreak investigations and for
      distinguishing between pathogenic and nonpathogenic organisms. STEC heart
      infusion washed blood agar with mitomycin-C (SHIBAM) is a modification of washed
      sheep blood  agar prepared by adding mitomycin-C and optimizing both the washed
      blood and base agar to better isolate STECs. Most STEC isolates produce a zone of
      hemolysis on SHIBAM plates and are easily distinguishable from background
      microbiota. Here, we present data supporting the use of SHIBAM to isolate  STECs
      from fresh produce. SHIBAM was tested for accuracy in identifying STECs (365 of
      410 STEC strains were hemolytic, and 63 of 73 E. coli strains that did not
      produce Shiga toxin were not hemolytic) and for recovery from artificially
      inoculated fresh produce (11 of 24 romaine lettuce  samples and 6 of 24 tomato
      samples). STEC recovery with SHIBAM agar was greatly improved when compared with
      recovery on Levine's eosin-methylene blue agar as a reference method.

PMID- 23127713
TI  - Quantitative risk assessment of verocytotoxin-producing Escherichia coli O157 and
      Campylobacter jejuni related to consumption of raw milk in a province in Northern
      Italy.
AB  - A quantitative risk assessment was developed to describe the risk of
      campylobacteriosis and hemolytic uremic syndrome (HUS) linked to consumption of
      raw milk sold in vending machines in Northern Italy. Exposure assessment
      considered the microbiological status of dairy farms, expected  milk
      contamination, storage conditions from bulk tank to home storage, microbial
      growth during storage, destruction experiments, consumption frequency of raw
      milk, age of consumers, serving size, and consumption preference. The
      differential risk between milk handled under regulation conditions  (4 degrees C
      throughout all phases) and the worst field handling conditions was considered.
      The probability of Campylobacter jejuni infection was modeled with a single-hit
      dose-response beta-Poisson model, whereas for HUS an exponential dose-response
      model was chosen and two probabilities  were used to model the higher
      susceptibility of children younger than 5 years old. For every 10,000 to 20,000
      consumers each year, the models predicted for the best and worst storage
      conditions, respectively, 2.12 and 1.14 campylobacteriosis cases and 0.02 and
      0.09 HUS cases in the 0- to 5-year  age group and 0.1 and 0.5 HUS cases in the >5
      year age group. The expected pediatric HUS cases do not differ considerably from
      those reported in Italy by the Minister of Health. The model developed may be a
      useful tool for extending the assessment of the risk of campylobacteriosis and
      HUS  due to raw milk consumption at the national level in Italy. Considering the
      epidemiological implications of this study, the risk of illness linked to raw
      milk consumption should not be ignored and could be reduced by the use of simple
      measures. Boiling milk before consumption and strict control  of temperatures by
      farmers during raw milk distribution have significant effects on
      campylobacteriosis and HUS and are essential measures for risk management.

PMID- 23127714
TI  - Sensitivity to pulsed light technology of several spoilage and pathogenic
      bacteria isolated from fish products.
AB  - The effect of pulsed light (PL) on the inactivation of six fish spoilage bacteria
      (Photobacterium phosphoreum, Serratia liquefaciens, Shewanella putrefaciens,
      Brochothrix thermosphacta, Pseudomonas group I, and Pseudomonas groups III and
      IV), six Listeria monocytogenes  isolates from fish products, and one strain of
      Listeria innocua was evaluated. For all tested strains, grown at 4 degrees C
      (temperature to process, store, and distribute convenient, lightly preserved fish
      products), the maximum detectable inactivation (6 to 6.5 log) was observed after 
      treatments lower than 0.3 J/cm(2). The most sensitive bacteria were P.
      phosphoreum and S. liquefaciens, while both L. innocua and L. monocytogenes were
      the most resistant species to PL. Bacterial inactivation kinetics depended on
      their susceptibility to  PL. Typically, sigmoidal curves were observed, with an
      initial shoulder followed by an exponential loss of cell culturability down to
      the maximum detectable inactivation. However, no initial shoulder was pointed out
      for the most sensitive species (P. phosphoreum and S. liquefaciens).  Since the
      PL resistance of all tested Listeria strains (L. innocua and L. monocytogenes
      isolates) was similar, we propose the use of L. innocua as a surrogate for L.
      monocytogenes in PL technology validation.

PMID- 23127715
TI  - Morphological, molecular, and mycotoxigenic identification of dominant
      filamentous fungi from moldy civil cheese.
AB  - Moldy Civil is a mold-ripened variety of cheese produced mainly in eastern
      Turkey. This cheese is produced with Civil cheese and whey curd cheese (Lor).
      Civil cheese has had a geographical presence since 2009 and is manufactured with
      skim milk. In the production of Moldy Civil cheese,  Civil cheese or a mixture of
      Civil and Lor cheese is pressed into goat skins or plastic bags and ripened for 3
      months or longer. During the ripening period, natural contaminating molds grow on
      the surface of and inside the cheese. In this study, 186 mold strains were
      isolated from 41 samples  of Moldy Civil cheese, and 165 of these strains were
      identified as Penicillium roqueforti. Identification and mycotoxicologic analyses
      were conducted using morphotypic and molecular methods. PCR amplicons of the ITS1
      5.8S-ITS4 region were subjected to sequence analysis. This research  is the first
      using molecular methods on Moldy Civil cheese. Mycotoxicologic analyses were
      conducted using thin-layer chromatography, and random amplified polymorphic DNA
      genotypes were determined using the ari1 primer. Of 165 isolates, only 28
      produced no penicillic acid, P. roqueforti  toxin, or roquefortine.

PMID- 23127716
TI  - Identification of unique food handling practices that could represent food safety
      risks for minority consumers.
AB  - Foodborne illness caused by Salmonella and Campylobacter is a concern for
      consumers, and there is evidence that minority racial-ethnic populations
      experience greater rates of illness because of these pathogens. The limited body
      of research concerning food safety knowledge  and practices among minority
      consumers has focused more on general food safety knowledge than on culturally
      specific food handling practices. The purpose of the research reported here was
      to explore food handling behaviors of minority racial-ethnic consumers through in
      depth discussions in  focus group settings. In this way, we hoped to identify
      potential unique, previously unidentified food handling practices among these
      consumers. Nine focus groups were held in Philadelphia, PA. Three focus groups
      were conducted with African American consumers, three with Hispanic consumers, 
      and three with Asian consumers. In all, 56 consumers participated. Data were
      recorded, transcribed, and analyzed for unique and potentially unsafe food
      handling behaviors. Potentially unsafe food handling practices identified among
      all three groups included extended time to transport food  from retail to home
      and washing of raw poultry. Culturally unique behaviors within groups included
      (i) using hot water (Asian, Hispanic) or acidic solutions (African American,
      Hispanic) to clean raw poultry, (ii) purchasing live poultry (Asian, Hispanic),
      (iii) cooking poultry overnight (African  American), and (iv) preparing bite-size
      pieces of meat prior to cooking (Asian, Hispanic). To have focus groups include a
      limited number of participants and nonrandom sampling means that these themes and
      trends cannot be extrapolated to represent food mishandling among these
      populations in  general. Results presented here allow modification of an existing
      food safety survey to identify the prevalence of these food handling practices
      among consumers of different demographics.

PMID- 23127717
TI  - Risk factors for microbial contamination in fruits and vegetables at the
      preharvest level: a systematic review.
AB  - The objective of this study was to perform a systematic review of risk factors
      for contamination of fruits and vegetables with Listeria monocytogenes,
      Salmonella, and Escherichia coli O157:H7 at the preharvest level. Relevant
      studies were identified by searching six electronic  databases: MEDLINE, EMBASE,
      CAB Abstracts, AGRIS, AGRICOLA, and FSTA, using the following thesaurus terms: L.
      monocytogenes, Salmonella, E. coli O157 AND fruit, vegetable. All search terms
      were exploded to find all related subheadings. To be eligible, studies had to be
      prospective controlled  trials or observational studies at the preharvest level
      and had to show clear and sufficient information on the process in which the
      produce was contaminated. Of the 3,463 citations identified, 68 studies fulfilled
      the eligibility criteria. Most of these studies were on leafy greens and
      tomatoes.  Six studies assessed produce contamination with respect to animal host
      related risk factors, and 20 studies assessed contamination with respect to
      pathogen characteristics. Sixty-two studies assessed the association between
      produce contamination and factors related to produce, water, and soil,  as well
      as local ecological conditions of the production location. While evaluations of
      many risk factors for preharvest-level produce contamination have been reported,
      the quality assessment of the reviewed studies confirmed the existence of solid
      evidence for only some of them, including  growing produce on clay-type soil, the
      application of contaminated or non-pH-stabilized manure, and the use of spray
      irrigation with contaminated water, with a particular risk of contamination on
      the lower leaf surface. In conclusion, synthesis of the reviewed studies suggests
      that reducing  microbial contamination of irrigation water and soil are the most
      effective targets for the prevention and control of produce contamination.
      Furthermore, this review provides an inventory of the evaluated risk factors,
      including those requiring more research.

PMID- 23127718
TI  - Management of microbial food safety in Arab countries.
AB  - Microbial food safety remains a major economic and public health concern in Arab
      countries. Over the past several years, many of these countries have attempted to
      revise and upgrade food quality control and surveillance programs; however, these
      systems vary in scope and effectiveness.  This review addresses the major
      reported foodborne outbreaks and multidrug resistance of pathogenic
      microorganisms isolated from food products. Major foodborne pathogens of concern
      included Brucella spp., Clostridium botulinum, fecal coliforms, Escherichia coli
      O157:H7,  Listeria monocytogenes, Salmonella, and Staphylococcus aureus. Measures
      for managing microbial food hazards based on a comprehensive risk analysis also
      are proposed.

PMID- 23127719
TI  - Neural stem cells and stroke.
AB  - Acute ischemic stroke causes a disturbance of neuronal circuitry and disruption
      of the blood-brain barrier that can lead to functional disabilities. At present,
      thrombolytic therapy inducing recanalization of the occluded vessels in the
      cerebral infarcted area is a commonly used therapeutic strategy. However, only a
      minority of patients have timely access to this kind of therapy. Recently, neural
      stem cells (NSCs) as therapy for stroke have been developed in preclinical
      studies. NSCs are harbored in the subventricular zone (SVZ) as well as the
      subgranular zone of the brain. The microenvironment in the SVZ, including
      intercellular interactions, extracellular matrix proteins, and soluble factors,
      can promote NSC proliferation, self-renewal, and multipotency. Endogenous
      neurogenesis responds to insults of ischemic stroke supporting the existence of
      remarkable plasticity in the mammalian brain. Homing and integration of NSCs to
      the sites of damaged brain tissue are complex morphological and physiological
      processes. This review provides an update on current preclinical cell therapies
      for stroke, focusing on neurogenesis in the SVZ and dentate gyrus and on
      recruitment cues that promote NSC homing and integration to the site of the
      damaged brain. 

PMID- 23127720
TI  - Spontaneous malignant glaucoma in a longstanding hypotonous eye.
AB  - A 38-year-old man with longstanding low intraocular pressure (IOP) in his right
      aphakic eye presented with severe pain and high IOP (35 mm Hg). On examination,
      visual acuity was light perception. The central and peripheral portions of the
      iris were directly opposed to the posterior corneal surface and synechial closure
      of the pupil margin. B-scan ultrasonography showed posterior vitreous detachment.
      The patient was treated with topical cycloplegics, a topical beta-blocker, and a
      systemic hyperosmotic agent. After 1 week, the anterior chamber was deep
      centrally, with peripheral synechiae between the iris and the cornea. The IOP of
      the right eye was 4 mm Hg. This case is an unusual spontaneous malignant glaucoma
      occurring in a longstanding hypotonous eye.

PMID- 23127721
TI  - Infections by gram-negative bacilli in patients with pulmonary arterial
      hypertension treated with intravenous prostacyclin.

PMID- 23127722
TI  - Oxidative proteome modifications target specific cellular pathways during
      oxidative stress, cellular senescence and aging.
AB  - Oxidatively modified proteins build-up with age results, at least in part, from
      the increase of reactive oxygen species and other toxic compounds originating
      from both cellular metabolism and external factors. Experimental evidence has
      also indicated that failure of protein maintenance is a major contributor to the
      age-associated accumulation of damaged proteins. We have previously shown that
      oxidized proteins as well as proteins modified by lipid peroxidation and
      glycoxidation adducts are accumulating in senescent human WI-38 fibroblasts and
      reported that proteins targeted by these modifications are mainly involved in
      protein maintenance, energy metabolism and cytoskeleton. Alterations in the
      proteome of human muscle adult stem cells upon oxidative stress have also been
      recently analyzed. The carbonylated proteins identified were also found to be
      involved in key cellular functions, such as carbohydrate metabolism, protein
      maintenance, cellular motility and protein homeostasis. More recently, we have
      built a database of proteins modified by carbonylation, glycation and lipid
      peroxidation products during aging and age-related diseases, such as
      neurodegenerative diseases. Common pathways evidenced by enzymes involved in
      intermediate metabolism were found targeted by these modifications, although
      different tissues have been examined. These results underscore the implication of
      potential deleterious effects of protein irreversible oxidative modifications in
      key cellular pathways during aging and in the pathogenesis of age-related
      diseases.

PMID- 23127723
TI  - Persistence of polycyclic aromatic hydrocarbons in sediments in the deeper area
      of the Northern Adriatic Sea (Mediterranean Sea).
AB  - The Po Valley is the most important agricultural and industrial area of Adriatic
      basin. In this area there are several rivers which transport polycyclic aromatic
      hydrocarbons (PAHs) into the sea via suspended particulate matter. This study
      describes the persistence of PAHs in the deep and coastal sediments of the
      Northern Adriatic. Different environmental conditions were studied: salinity,
      temperature, sunlight, sediment particle size and organic matter in sediment. The
      average conditions in the deep areas of the Northern Adriatic are: salinity
      higher than 37, temperature lower than 11  degrees C, darkness and clayey
      sediments with a high organic matter content. These conditions increase the
      persistence of the PAHs in the deep area of the Northern Adriatic.

PMID- 23127724
TI  - Lability of potentially toxic elements in soils affected by smelting activities.
AB  - Determination of total concentration of potentially toxic elements (PTEs) in soil
      is not a reliable tool for evaluating potential exposure risk for humans. PTE
      lability (EDTA, SBET and solution extraction) and chemical speciation (BCR
      sequential extraction) were investigated for Pb, Cd, Cu, and Zn, as well as how
      these could be affected by flooding in soils polluted by smelting activities. The
      flooding experiment was performed in pots from which soil solution was extracted
      at different time intervals using Rhizon Moisture Samplers. After experiments,
      the soil was again subjected to the previous extractions (EDTA, SBET, and BCR) in
      order to reveal the changes which occurred during anoxia. From the results we can
      conclude that PTE lability is very high and flooding caused the increase in their
      mobility up to 100% (for bioaccessible Pb). The experiment demonstrated that
      temporary reducing conditions can increase the risk of contaminants passing to
      other environmental compartments and the food chain.

PMID- 23127725
TI  - Respiratory sinus arrhythmia, shyness, and effortful control in preschool-age
      children.
AB  - Resting respiratory sinus arrhythmia (RSA) and shyness were examined as
      predictors of effortful control (EC) in a sample of 101 preschool-age children.
      Resting RSA was calculated from respiration and heart rate data collected during
      a neutral film; shyness was measured using parents', preschool teachers', and
      classroom observers' reports; and EC was measured using four laboratory tasks in
      addition to questionnaire measures. Principal components analysis was used to
      create composite measures of EC and shyness. The relation between RSA and EC was
      moderated by shyness, such that RSA was positively related to EC only for
      children high in shyness. This interaction suggests that emotional reactivity
      affects the degree to which RSA can be considered a correlate of EC. This study
      also draws attention to the need to consider the measurement context when
      assessing resting psychophysiology measures; shy individuals may not exhibit true
      baseline RSA responding in an unfamiliar laboratory setting.

PMID- 23127726
TI  - More is not necessarily better. A biomechanical study on distal screw numbers in
      volar locking distal radius plates.
AB  - INTRODUCTION: Currently available volar locking plates for the treatment of
      distal radius fractures incorporate at least two distal screw rows for fixation
      of the metaphyseal fragment and have a variable-angle locking mechanism which
      allows placement of the screws in various directions There is, however no
      evidence that these plates translate into better outcomes or have superior
      biomechanical properties to first generation plates, which had a single distal
      screw row and fixed-angle locking. The aim of our biomechanical study was to
      compare fixed-angle single-row plates with variable-angle multi-row plates to
      clarify the optimal number of locking screws. MATERIALS AND METHODS: Five
      different plate-screw combinations of three different manufacturers were tested,
      each group consisting of five synthetic fourth generation distal radius bones. An
      AO type C2 fracture was created and the fractures were plated according to each
      manufacturer's recommendations. The specimens then underwent cyclic and load-to
      failure testing. An optical motion analysis system was used to detect
      displacement of fragments. RESULTS: No significant differences were detected
      after cyclic loading as well as after load-to-failure testing, neither in regard
      to axial deformation, implant rigidity or maximum displacement. The fixed-angle
      single-row plate showed the highest pre-test rigidity, least increase in post
      testing rigidity and highest load-to-failure rigidity and least radial
      shortening. The radial shortening of plates with two distal screw rows was 3.1
      and 4.3 times higher, respectively, than that of the fixed-angle single-row
      plate. CONCLUSION: The results of our study indicate that two distal screw rows
      do not add to construct rigidity and resistance against loss of reduction. Well
      conducted clinical studies based on the findings of biomechanical studies are
      necessary to determine the optimal number of screws necessary to achieve
      reproducibly good results in the treatment of distal radius fractures.

PMID- 23127727
TI  - A major haemorrhage protocol improves the delivery of blood component therapy and
      reduces waste in trauma massive transfusion.
AB  - BACKGROUND: Major haemorrhage protocols (MHP) are required as part of damage
      control resuscitation regimens in modern trauma care. The primary objectives of
      this study were to ascertain whether a MHP improved blood product administration
      and reduced waste compared to traditional massive transfusion protocols (MTP).
      METHODS: Datasets on adult trauma admissions 1 year prior and 1 year post
      implementation of a MHP at a Level 1 trauma centre were obtained from the trauma
      registry. Demographic and clinical data were collected prospectively including
      mechanism of injury, physiological observations, ICU admission and length of
      stay. The volume of blood components (packed red blood cells, platelets,
      cryoprecipitate and fresh frozen plasma) issued, transfused, returned to stock
      and wasted within the first 24h was gathered retrospectively. RESULTS: Over the 2
      year study period 2986 patient records were available for analysis. 40 patients
      required a 10+ Units of packed red blood ells transfusion in the MTP group vs. 56
      patients post MHP implementation. The administration of blood component therapy
      improved significantly post MHP implementation. FFP:PRBC transfusion improved
      from 1:3 to 1:2 (p<0.01) and CRYO:PRBC improved from 1:10 to 1:7 (p<0.05). We
      reported a significant reduction in the waste of platelets from 14% to 2%
      (p<0.01). Outcomes had improved: Median hospital length of stay was reduced from
      54 days to 26 days (p<0.05). CONCLUSION: Implementation of a MHP results in
      improved delivery of blood components and a reduction in the waste of blood
      products compared to the older model of MTP. In combination with educational
      programmes MHP can significantly improve blood product administration and patient
      outcomes in trauma haemorrhage. LEVEL OF EVIDENCE: Level III diagnostic test
      study.

PMID- 23127728
TI  - Efficacy of intranasal steroid spray (mometasone furoate) on treatment of
      patients with seasonal allergic rhinitis: comparison with oral corticosteroids.
AB  - OBJECTIVE: Intranasal corticosteroids are effective for allergic rhinitis and
      broadly used in daily clinical practice. Systemic oral corticosteroids are also
      known to be effective for treatment of allergic rhinitis. These topical and
      systemic corticosteroids are both effective formulations for allergic rhinitis,
      and both drugs have some side effects. When treatment formulations for allergic
      rhinitis are selected based on side effects, topical corticosteroids are more
      commonly selected than systemic steroids. Systemic corticosteroids, on the other
      hand, have traditionally been believed to have higher and more instantaneous
      therapeutic effects than those of topical corticosteroids. However, there have
      been few reports of direct comparisons between topical corticosteroid and
      systemic corticosteroid efficacy. The purpose of this study was to evaluate the
      subjective outcomes of nasal symptom management using topical intranasal
      corticosteroid therapy or systemic oral corticosteroid therapy in patients with
      seasonal allergic rhinitis. We compared the efficacy of mometasone furoate nasal
      spray (MFNS) to betamethasone oral tablets (BOT) for the treatment of patients
      with seasonal allergic rhinitis. METHODS: In an open label study, patients with
      seasonal allergic rhinitis who had intermediate-to-severe symptoms and who
      visited the hospital without prior treatment were allocated to 1 of 3 treatment
      groups (noncorticosteroid group, topical corticosteroid group, and oral
      corticosteroid group). Evaluation was conducted using allergy diaries that
      consisted of patient questionnaires. The Japanese Rhinoconjunctivitis Quality of
      Life Questionnaire (JRQLQ) was used in this study. RESULTS: Compared to only
      loratazine nonsteroid therapy, both MFNS 200MUg once daily and BOT 0.25mg twice
      daily significantly reduced the total and individual symptom scores for sneezing,
      nasal obstruction, watery nasal discharge, and nasal itching (P<0.05). Scores for
      itching of the eyes were reduced slightly more in the MFNS group than in the
      noncorticosteriod treatment group, but the difference was not significant.
      CONCLUSION: MFNS and BOT have virtually equivalent effects on nasal symptoms in
      patients with seasonal allergies. Our study was the first direct comparison
      between an intranasal corticosteroid spray and a systemic oral corticosteroid for
      seasonal allergic rhinitis. No significant differences were found in the
      therapeutic effects of the topical and systemic corticosteroids tested,
      suggesting that topical corticosteroids are expected to sufficiently improve
      nasal symptoms without administration of oral corticosteroids. Treatment with
      intranasal corticosteroid spray is more strongly recommended than treatment with
      systemic corticoid steroids, due to the side effects associated with each
      treatment.

PMID- 23127729
TI  - Clostridium difficile: the emerging epidemic.

PMID- 23127730
TI  - Little hope for medical futility.

PMID- 23127731
TI  - Clostridium difficile infection in patients with chronic kidney disease.
AB  - OBJECTIVE: To examine the rate of Clostridium difficile infection (CDI) and
      hospital-associated outcomes in a national cohort of hospitalized patients with
      chronic kidney disease (CKD) and assess the impact of long-term dialysis on
      outcome in these patients. PATIENTS AND METHODS: Data for January 1, 2005,
      through December 31, 2009 were obtained from the National Hospital Discharge
      Survey, which includes information on patient demographics, diagnoses,
      procedures, and discharge types. Data collected and analyzed for this study
      included age, sex, race, admission type (urgent or emergent combined vs
      elective), any colectomy diagnosis, length of stay, type of discharge, and
      mortality. International Classification of Diseases, Ninth Revision, Clinical
      Modification codes were utilized to identify CKD patients and CDI events.
      Weighted analysis was performed using JMP version 9. RESULTS: An estimated 162
      million adults were hospitalized during 2005-2009, and 8.03 million (5%) had CKD
      (median age, 71 years). The CDI rate in CKD patients was 1.49% (0.119 million)
      compared with 0.70% (1.14 million) in patients without CKD (P<.001). Patients
      with CKD who were undergoing long-term dialysis were more than 2 times as likely
      to develop CDI than non-CKD patients and 1.33 times more likely than CKD patients
      not undergoing dialysis (all P<.001). In a weighted multivariate analysis
      adjusting for sex and comorbidities, patients with CKD and CDI had longer
      hospitalization, higher colectomy rate (adjusted odds ratio [aOR], 2.30; 95%
      confidence interval [CI], 2.14-2.47), dismissal to a health care facility (aOR,
      2.22; 95% CI, 2.19-2.25), and increased in-hospital mortality (aOR, 1.55; 95% CI,
      1.52-1.59; all P<.001) as compared with CKD patients without CDI. Patients with
      CKD who were undergoing long-term dialysis did not have worse outcomes as
      compared with CKD patients who were not undergoing long-term dialysis.
      CONCLUSION: These data suggest that patients with CKD have a higher risk of CDI
      and increased hospital-associated morbidity and mortality. Future prospective
      studies are needed to confirm these findings and to identify effective CDI
      prevention in CKD patients, who appear to have an increased risk of CDI
      acquisition.

PMID- 23127732
TI  - Temporal trends in the incidence of surgical site infections in patients
      undergoing coronary artery bypass graft surgery: a population-based cohort study,
      1993 to 2008.
AB  - OBJECTIVE: To determine the incidence of and temporal trends in surgical site
      infections (SSIs) in patients undergoing coronary artery bypass graft (CABG)
      surgery. METHODS: A population-based cohort study was conducted to describe the
      epidemiologic features of SSI in Olmsted County, Minnesota, between January 1,
      1993, and December 31, 2008, using the Rochester Epidemiology Project. Period
      specific incidence rates (in-hospital or within 30 days outside the hospital)
      were calculated. Logistic regression analysis was used to adjust for potential
      confounders that could affect temporal trends in SSI incidence rates. RESULTS:
      During the 16-year study, of 1424 residents of Olmsted County who underwent CABG
      surgery, 1189 (83%) had isolated CABG and 235 (17%) had combined CABG and valve
      surgery. The overall SSI incidence rate was 7.0% (95% confidence interval [CI],
      5.7%-8.4%). The incidence rate of superficial sternal SSI was 2.0% (95% CI, 1.2%
      2.7%) and of deep sternal SSI was 1.5% (95% CI, 0.9%-2.2%). The leg harvest site
      infection rate was 3.6% (95% CI, 2.6 %-4.5%). The incidence rate decreased over
      time with a statistically significant linear trend. The adjusted odds ratio (95%
      CI) of SSI showed a decreasing linear trend: 0.39 (0.19-0.81) vs 0.50 (0.27-0.93)
      vs 0.83 (0.48-1.42) vs reference for 2005-2008 vs 2001-2004 vs 1997-2000 vs 1993
      1996. CONCLUSION: In this population-based surveillance study of patients
      undergoing CABG surgery, the incidence of SSI decreased markedly between 1993 and
      2008 in patients in Olmsted County. The factors responsible for this decrease are
      the focus of ongoing investigations.

PMID- 23127733
TI  - Pericardiectomy vs medical management in patients with relapsing pericarditis.
AB  - OBJECTIVE: To determine whether surgical pericardiectomy is a safe and effective
      alternative to medical management for chronic relapsing pericarditis. PATIENTS
      AND METHODS: Retrospective review of 184 patients presenting to the Mayo Clinic
      in Rochester, Minnesota, from January 1, 1994, through December 31, 2005, with
      persistent relapsing pericarditis identified 58 patients who had a
      pericardiectomy after failed medical management and 126 patients who continued
      with medical treatment only. The primary outcome variables were in-hospital
      postoperative mortality or major morbidity, all-cause death, time to relapse, and
      medication use. RESULTS: Mean +/- SD follow-up was 5.5 +/- 3.5 years in the
      surgical group and 5.4 +/- 4.4 years in the medical treatment group. At baseline,
      patients in the surgical group had higher mean relapses (6.9 vs 5.5; P=.01), were
      more likely to be taking colchicine (43.1% [n=25] vs 18.3% [n=23]; P=.002) and
      corticosteroids (70.7% [n=41] vs 42.1% [n=53]; P<.001), and were more likely to
      have undergone a prior pericardiotomy (27.6% [n=16] vs 11.1% [n=14]; P=.003) than
      the medical treatment group. Perioperative mortality (0%) and major morbidity
      (3%; n=2) were minimal. Kaplan-Meier analysis revealed no differences in all
      cause death at follow-up (P=.26); however, the surgical group had a markedly
      decreased relapse rate compared with the medical treatment group (P=.009).
      Medication use was notably reduced after pericardiectomy. CONCLUSION: In patients
      with chronic relapsing pericarditis in whom medical management has failed,
      surgical pericardiectomy is a safe and effective method of relieving symptoms.

PMID- 23127734
TI  - End-of-life care decisions: importance of reviewing systems and limitations after
      2 recent North American cases.
AB  - Two recent and unfortunate North American cases involving end-of-life treatment
      highlight the difficulties surrounding medical futility conflicts. As countries
      have explored the greater influence that patients and their representatives may
      play on end-of-life treatment decisions, the benefits and struggles involved with
      such a movement must be appreciated. These 2 cases are used to examine the
      present systems existing in the United States and Canada for resolving end-of
      life decisions, including the difficulty in defining medical futility, the role
      of medical ethics committees, and controversies involving surrogate decision
      making.

PMID- 23127736
TI  - Clinical pearls in palliative medicine 2012.

PMID- 23127735
TI  - Clostridium difficile infection: new insights into management.
AB  - Clostridium difficile was first described as a cause of diarrhea in 1978 and is
      now among the leading 3 hospital-acquired infections in the United States, along
      with methicillin-resistant Staphylococcus aureus and vancomycin-resistant
      enterococci. In the past 2 decades, there has been an increase in the incidence,
      severity, and recurrence rates of C difficile infection, all of which are
      associated with poor outcomes. In addition, several novel risk factors and newer
      treatment methods are emerging, including fidaxomicin therapy, treatment using
      monoclonal antibodies, and fecal microbiota transplantation, that have shown
      promise for the treatment of C difficile infection. This review focuses on the
      changing epidemiology, risk factors, and newer methods for treatment of C
      difficile infection.

PMID- 23127737
TI  - 48-Year-old woman with dyspnea, cough, and weight loss.

PMID- 23127739
TI  - Oropharyngeal cancer biology and treatment: insights from messenger RNA sequence
      analysis and transoral robotic surgery.

PMID- 23127741
TI  - Potential, but unobserved, adverse cardiovascular effects from endurance
      exercise.

PMID- 23127742
TI  - 57-Year-old man with fever, rash, chronic watery diarrhea, cough, and sweats.

PMID- 23127743
TI  - 74-Year-old man with palpitations.

PMID- 23127744
TI  - Prince Wongsa Dhiraj Snid--Thai physician and diplomat.

PMID- 23127746
TI  - Rapid resolution of uremic tumoral calcinosis after parathyroidectomy.

PMID- 23127747
TI  - Characterization of structure-antioxidant activity relationship of peptides in
      free radical systems using QSAR models: key sequence positions and their amino
      acid properties.
AB  - Antioxidative peptides have attracted increasing attention from researchers
      because of their antioxidant properties as natural materials in functional food
      and for applications in medicine. However, the relationship between structure and
      activity (SAR) remains unclear, especially in antioxidative peptides in free
      radical systems. Antioxidative peptides with different lengths were obtained from
      the literature, measured using different methods, and were organized into three
      databases, namely, Trolox-equivalent antioxidant capacity (TEAC), oxygen radical
      absorption capacity (ORAC), and superoxide radical (SOR). After the peptides were
      processed using the two-terminal position numbering method, quantitative SAR
      modeling was performed on antioxidative peptides in the three databases. The
      vectors of hydrophobic, steric, and electronic properties (VHSE) and the divided
      physicochemical property scores descriptors (DPPS) were selected from 17
      physicochemical descriptors to express electronic, hydrophobic, and steric
      properties (or hydrogen bonding) of the three (or four) external amino acids in
      the N-terminal and C-terminal positions. Models were estimated using partial
      least squares regression and validated through full cross-validation and external
      validation (R(2)>0.7, Q(2)>0.5 for TEAC; R(2)>0.9, Q(2)>0.5 for ORAC and SOR).
      The results found a relationship between the physicochemical properties of the C
      terminal and N-terminal regions and antioxidant potency. The properties of amino
      acids at C-terminal regions were more important than those at the N-terminal
      regions for predicting antioxidant activity. The properties of amino acids at
      C(2)>C(1) for TEAC, C(3)>C(4)>C(1) for ORAC, and C(4)>C(1)>N(1) for SOR were
      highly correlated with antioxidant activity. Although electronic property most
      significantly contributed to antioxidant activity in the three free radical
      systems, it had complex effects at each position. Bulky hydrophobic amino acids
      at the C-terminal were related to the antioxidant activity of peptides in the
      three free radical systems. For peptides in the TEAC database, the relationship
      between the N-terminal segment (N(2), N(3)) and the activity increased when
      longer peptides were included, which reflects the likely influence of stericity.
      This study contributes to the ongoing research on antioxidants in food and its
      application in medicine.

PMID- 23127748
TI  - In vivo confocal microscopy in diagnosis of limbal stem cell deficiency.
AB  - PURPOSE: To correlate in vivo confocal microscopy and impression cytology
      features of the corneal surface epithelia in patients with clinical features of
      partial or total limbal stem cell deficiency and to examine the limbal
      morphology. DESIGN: Prospective case-control observational study. METHODS: Twenty
      eyes of 17 consecutive patients (mean age 53.9 +/- 9.2 years) presenting with
      clinical suspect of limbal stem cell deficiency and 10 eyes of 10 healthy control
      subjects were enrolled. In vivo confocal microscopy and impression cytology (PAS,
      cytokeratin 12, and cytokeratin 19) staining were performed in the central
      cornea. The inter-examination agreement was determined. Confocal microscopy scans
      were obtained in all patients to assess microscopic structure of the
      corneoscleral limbus, in all quadrants. RESULTS: Confocal microscopy and
      impression cytology agreement in testing the diagnostic hypotheses was high
      (kappa = 0.85). The 2 methods were concordant in 18 out of 20 examined eyes
      (90%), revealing the presence of just corneal epithelium in 7 cases, just
      conjunctival epithelium (total limbal stem cell deficiency) in 5 cases, and mixed
      epithelium in 6 cases (partial limbal stem cell deficiency). Confocal imaging of
      the limbus revealed normal palisades of Vogt structure and epithelial transition
      in the healthy eyes while demonstrating a variable degree of alterations,
      including loss of the limbal palisades and of the normal epithelial mosaic,
      cystic epithelial changes, and subepithelial fibrosis, in the eyes affected by
      partial or total limbal stem cell deficiency. CONCLUSIONS: Confocal microscopy
      was useful for the noninvasive in vivo diagnosis of limbal stem cell deficiency,
      with a high degree of concordance with impression cytology, and to detect limbal
      alterations associated with partial or total conjunctivalization of the cornea.

PMID- 23127749
TI  - Biometric and molecular characterization of clinically diagnosed posterior
      microphthalmos.
AB  - PURPOSE: To biometrically and molecularly characterize clinically diagnosed
      posterior microphthalmos. DESIGN: Prospective case series. METHODS: Twenty-five
      affected patients from 13 families diagnosed by ophthalmologists experienced with
      the condition at the King Khaled Eye Specialist Hospital were studied. All
      participants underwent axial length measurement, keratometry, corneal pachymetry,
      and candidate gene analysis (MFRP, PRSS56). Main outcome measures were the
      results of ocular biometry and gene analysis. RESULTS: All patients (2-47 years
      of age) had high hyperopia, normal-appearing anterior segments, posterior chamber
      foreshortening, and characteristic papillomacular folds/wrinkles. For the right
      eye, mean cycloplegic refraction was +15.09 diopters (D) (range 9.88-18.75).
      Axial length (mean 16.25 mm [range 14.88-19.88]) had strong inverse correlation
      (Pearson coefficient -0.88, P < .0001) with corneal power (mean 48.89 D [range
      41.91-52.25]) and a positive correlation with corneal diameter (Pearson 0.64, P =
      .001). Corneal thickness and anterior chamber dimensions were within normal
      ranges. Left eye data were similar. Nineteen Saudi patients (8/13 families)
      harbored 4 different homozygous PRSS56 mutations, 1 Indian and 1 Saudi patient
      harbored 2 different homozygous MFRP mutations, and 4 Saudi patients (3/13
      families) had no detectable mutation in either gene. Patients with MFRP mutations
      were not clinically different from patients with PRSS56 mutations or no
      identified mutation. Truncating PRSS56 mutations were associated with shorter
      axial lengths (mean 15.72 mm) than missense PRSS56 mutations (mean 16.37 mm) or
      no identified mutation (mean 17.57 mm). CONCLUSIONS: These data define posterior
      microphthalmos biometrically and reveal that corneal steepening proportional to
      the degree of axial foreshortening is part of the phenotype. Corneal diameter
      decreases with decreasing axial length, suggesting posterior microphthalmos and
      nanophthalmos represent a spectrum of high hyperopia rather than distinct
      phenotypes. In the Saudi population PRSS56 mutations are the major cause, and in
      our cohort truncating mutations were associated with a more severe phenotype.

PMID- 23127750
TI  - Three-dimensional tomographic features of dome-shaped macula by swept-source
      optical coherence tomography.
AB  - PURPOSE: To study the tomographic and pathomorphologic features of dome-shaped
      maculas with swept-source optical coherence tomography (OCT). DESIGN:
      Prospective, cross-sectional study. METHODS: The macular area of 51 highly myopic
      eyes (35 patients) with dome-shaped maculas was studied with swept-source OCT at
      1050 nm. Three-dimensional (3-D) data sets were obtained with raster scanning
      covering a 12 * 8-mm(2) area; 3-D images of the posterior pole were constructed
      by autosegmentation of the retinal pigment epithelium (RPE). RESULTS: In all
      reconstructed 3-D images of the RPE, 2 outward concavities were seen within the
      posterior staphyloma and a horizontal ridge was formed between these 2
      concavities. In 42 of these eyes, this horizontal ridge was band shaped. The
      vertical OCT section through the fovea showed a convex configuration of RPE, but
      the horizontal section showed an almost flat RPE line. In 9 eyes, 3-D images
      showed a typical dome-shaped convexity within the staphyloma. OCT scans showed no
      outward protrusions in the external scleral surface, but marked scleral thinning
      was seen consistent with the 2 outward concavities of the RPE. The sclera of the
      fovea (518.6 +/- 97.6 MUm) was significantly thicker than that in all 4 quadrants
      of the parafoveal area (range, 277.2 to 360.3 MUm; P < .001). CONCLUSIONS: In
      highly myopic eyes with a dome-shaped macula, a horizontal ridge is formed within
      the posterior staphyloma by uneven thinning of the sclera.

PMID- 23127751
TI  - Normative reference ranges for the retinal nerve fiber layer, macula, and retinal
      layer thicknesses in children.
AB  - PURPOSE: To establish a normative database of peripapillary retinal nerve fiber
      layer (RNFL) thickness, macular thickness, and retinal layer thickness in healthy
      North American children, using spectral-domain optical coherence tomography (SD
      OCT). DESIGN: Prospective cross-sectional study. METHODS: This institutional
      study enrolled 83 healthy children (aged 5-15 years) as volunteer research
      subjects at the Retina Foundation of the Southwest (Dallas, Texas); all had
      normal visual acuity. Imaging was accomplished with the Spectralis SD OCT.
      Peripapillary RNFL thickness and macular thickness were assessed for 1 eye of
      each child using the Heidelberg Spectralis SD OCT software. Thicknesses of
      individual retinal layers and layer combinations were assessed using custom
      software to segment the line scans obtained with the Spectralis SD OCT. RESULTS:
      Average global peripapillary RNFL thickness was 107.6 +/- 1.2 MUm and average
      central subfield macular thickness was 271.2 +/- 2.0 MUm. Peripapillary RNFL
      thickness was thicker than has been reported in adults, particularly the superior
      and inferior sectors, and central subfield macular thickness was significantly
      correlated with age. While the thickness of most retinal layers was comparable
      with those of adults, the outer segment layer was 36% thinner in children than in
      adults. CONCLUSIONS: SD OCT can be used to assess peripapillary RNFL thickness,
      macular thickness, and retinal layer thickness in children as young as 5 years.
      Pediatric means and normative reference ranges are provided for each measurement.
      The values presented herein can be used as a standard with which to compare those
      of children suspected of having retinal or optic nerve abnormalities.

PMID- 23127753
TI  - Genetic encoding of fluorescent RNA ensures a bright future for visualizing
      nucleic acid dynamics.
AB  - Recently RNA localization has been appreciated as an essential post
      transcriptional mechanism to program local proteome composition and function.
      Although RNA has been visualized using diverse techniques, the use of the
      bacteriophage MS2 method to encode genetically fluorescent RNA has revolutionized
      the study of RNA dynamics in living cells. Here, I highlight the strength of MS2
      compared to other techniques, and how further evolution of this system will
      enable the visualization of RNA in the context of complex live-cell dynamics.
      Although the generation of MS2-fluorescence resonance energy transfer (FRET) and
      MS2-bifluorescence complementation (BiFC) will require further development, it
      has the potential to increase significantly the signal-to-noise ratio, which is
      the major obstacle to rapid live-cell imaging of RNA.

PMID- 23127754
TI  - Effects of chronic sildenafil use on pulmonary hemodynamics and clinical outcomes
      in heart transplantation.
AB  - BACKGROUND: Elevated pulmonary vascular resistance (PVR) in heart transplant (HT)
      candidates is associated with poor survival after HT. This study assessed the
      effect of peri-operative sildenafil administration on pulmonary hemodynamics and
      clinical outcomes in patients with advanced heart failure who were considered
      high-risk for HT because of elevated PVR and transpulmonary gradient (TPG).
      METHODS: The study included 119 consecutive patients who underwent HT between
      2004 and 2011. Fifteen patients (Group A) had severe pulmonary hypertension (PH),
      defined as mean pulmonary pressure (MPAP)>25 mm Hg and PVR>2.5 Wood units (WU),
      and/or TPG>12 mm Hg after vasodilator test or the continuous administration of
      inotropics drugs, and 104 patients (Group B) were without severe PH. Group A
      received sildenafil therapy. Pulmonary hemodynamics were evaluated before HT with
      and without sildenafil therapy. Right catheterization was performed early after
      HT with sildenafil therapy and late after HT without sildenafil. Survival after
      HT was compared between the groups. RESULTS: The sildenafil dosage was 109+/-42
      mg/day during 163+/-116 days before HT. After sildenafil therapy MPAP, PVR, and
      TPG decreased from 43.9+/-12.5 to 33.4+/-5.8 mm Hg, 5.0+/-1.1 to 3.0+/-1.6 WU,
      and 17.3+/-3.2 to 10.2+/-4.1 mm Hg, respectively (p<.01). All patients underwent
      successful HT. Sildenafil dosage was 140+/-70 mg/day for 43+/-45 days after HT.
      There were no differences in PVR and TPG with sildenafil therapy early after HT
      and without sildenafil 6 months after HT. Survival after HT was similar between
      the groups. CONCLUSION: Sildenafil therapy before and after HT in patients with
      severe PH is associated with improved pulmonary hemodynamics and successful HT,
      without an increase in post-HT mortality.

PMID- 23127756
TI  - PET imaging of serotonin transporters with 4-[18F]-ADAM in a Parkinsonian rat
      model.
AB  - This study was undertaken to address the effects of fetal mesencephalic tissue
      transplantation on the serotonin system in a rat model of Parkinson's disease
      (PD) while also investigating the usefulness of 4-[18F]-ADAM (a serotonin
      transporter imaging agent) coupled with micro-PET for imaging serotonin
      transporters (SERTs). A PD model was induced by unilateral injection of 6
      hydroxydopamine (6-OHDA) into the right medial forebrain bundle of the
      nigrostriatal pathway, while cell transplantation was performed via intrastriatal
      injection of mesencephalic brain tissue dissected from embryonic (E14) rats. The
      4-[18F]-ADAM/micro-PET scanning was performed following both 6-OHDA lesioning and
      transplantation. Immunohistochemistry (IHC) studies were also performed following
      the final PET scan, and the results were compared to show a 17-43% decrease in
      the specific uptake ratio (SUR) and a 23-52% decrease in serotonin transporter
      immunoreactivity (SERT-ir) within various brain regions on the lesioned side. The
      number of methamphetamine-induced rotations also decreased significantly at the
      4th week postgraft. In addition, striatal SUR and the SERT-ir levels were
      restored to 77% and 83% 5 weeks postgraft. These results suggest that Parkinson's
      disease also affects the serotonergic system, while both the dopaminergic and
      serotonergic systems can be partially restored in a rat model of PD after E14
      mesencephalic tissue transplantation. In addition, we have also determined that 4
      [18F]-ADAM/micro-PET can be used to detect serotonergic neuron loss, monitor the
      progress of Parkinson's disease, and oversee the effectiveness of therapy.

PMID- 23127757
TI  - Stem cell applications in regenerative medicine for neurological disorders.
AB  - Stem cells are capable of self-renewal and differentiation into a wide range of
      cell types with multiple clinical and therapeutic applications. Stem cells are
      providing hope for many diseases that currently lack effective therapeutic
      methods, including stroke, amyotrophic lateral sclerosis, Alzheimer's disease,
      and Parkinson's disease. Embryonic stem (ES) cells were originally targeted for
      differentiation into functional dopamine neurons for cell therapy. Today, induced
      pluripotent stem (iPS) cells are being tested for such purposes as generating
      functional dopamine neurons and treating a rat model of Parkinson's disease. In
      addition, neural stem cell and mesenchymal stem cells are also being used in
      neurodegenerative disorder therapies for stroke and Parkinson's disease. Although
      stem cell therapy is still in its infancy, it will likely become a powerful tool
      for many diseases that currently do not have effective therapeutic approaches. In
      this article, we discuss current research on the potential application of neural
      stem cells, mesenchymal stem cells, ES cells, and iPS cells to neurodegenerative
      disorders. 

PMID- 23127755
TI  - New models for analyzing mast cell functions in vivo.
AB  - In addition to their well-accepted role as critical effector cells in anaphylaxis
      and other acute IgE-mediated allergic reactions, mast cells (MCs) have been
      implicated in a wide variety of processes that contribute to disease or help to
      maintain health. Although some of these roles were first suggested by analyses of
      MC products or functions in vitro, it is critical to determine whether, and under
      which circumstances, such potential roles actually can be performed by MCs in
      vivo. This review discusses recent advances in the development and analysis of
      mouse models to investigate the roles of MCs and MC-associated products during
      biological responses in vivo, and comments on some of the similarities and
      differences in the results obtained with these newer versus older models of MC
      deficiency.

PMID- 23127758
TI  - First report on exploring structural requirements of 1,2,3,4- tetrahydroacridin
      9(10H)-one analogs as antimalarials using multiple QSAR approaches: descriptor
      based QSAR, CoMFA-CoMSIA 3DQSAR, HQSAR and G-QSAR approaches.
AB  - Due to the emergence of multidrug resistance of malaria parasites, there is an
      urgent need to modify existing antimalarial drugs through structural changes as
      well as to search new pharmacophores to counteract the induced resistance. In the
      present work, different quantitative structure-activity relationship (QSAR)
      models have been developed using a series of 73 1,2,3,4-tetrahydroacridin-9(10H)
      one (THA) analogs with well defined antimalarial activity against W2 clone to
      provide detailed insight into the main structural fragments that impart
      antimalarial activity to these molecules. To the best of our knowledge, this is
      first QSAR report of THA analogs as antimalarials. From the developed models, it
      may be inferred that for an enhancement in the antimalarial activity of the
      molecules: i) R2 position should be substituted with a bulky group (like phenyl,
      methoxy, isopropyl, tertiary butyl group) which may be further substituted with
      electrostatically favored positively charged group; ii) R3 position should be
      substituted with hydrophobically favored but sterically disfavored group; iii) R4
      position should be substituted with positively charged group lacking any carbon
      atom and iv) R5 position should be substituted with two methyl groups. On the
      contrary, substitution with bulky group at R6 position may reduce the
      antimalarial activity. Using the developed models, we have designed and proposed
      some new compounds which showed good in silico predicted activity. The designed
      compounds may be experimentally proved to be active and useful THA derivatives as
      antimalarial compounds.

PMID- 23127759
TI  - Allele frequencies of the new European Standard Set (ESS) loci in a population of
      Apulia (Southern Italy).
AB  - Allele frequencies of five miniSTRs loci (D1S1656, D2S441, D12S391, D10S1248 and
      D22S1045) included in the new European Standard Set (ESS) were calculated from a
      sample of 150 unrelated individuals from Apulia, a Region of Southern Italy. Two
      different PCR Amplification Kits were used, in order to evaluate the concordance
      of the genotypes. The results obtained with the two kits showed no differences in
      all genotype profiles. No deviation from Hardy-Weinberg expectations was detected
      at either locus. Moreover genetic analysis using Fst estimation showed no
      evidence for differentiation at the five new loci between Apulia and Italian
      populations. The high levels of polymorphisms of the analyzed markers in the
      Apulian population allow to confirm that these markers are useful tools in
      paternity and forensic analysis from degraded DNA samples.

PMID- 23127760
TI  - Genetics of atherosclerosis and vascular calcification go hand-in-hand.

PMID- 23127761
TI  - Casitas B-lineage lymphoma mutants activate AKT to induce transformation in
      cooperation with class III receptor tyrosine kinases.
AB  - In addition to overexpression and the occurrence of activating mutations,
      receptors can be aberrantly activated by impaired downregulation. In this study,
      we show that an oncogenic mutant of the ubiquitin ligase casitas B-lineage
      lymphoma (CBL; CBLDeltaexon8), which is found in acute myeloid leukemia patients,
      predominantly cooperates with receptor tyrosine kinase (RTK) class III receptors
      (PDGFRA, PDGFRB, KIT, and FLT3), but not with non-class III RTKs or cytokine
      receptors, to induce IL-3-independent growth of Ba/F3 cells. In cells
      coexpressing RTK class III/CBLDeltaexon8, receptor internalization was delayed,
      and cells were protected from apoptosis after cytokine withdrawal. Ligand
      stimulated Ba/F3 cells and acute myeloid leukemia cell lines coexpressing the CBL
      deletion mutant and FLT3 showed enhanced AKT phosphorylation. Combined
      pharmacologic inhibition of the PI3K/AKT pathway and FLT3 had an additive effect
      on cell proliferation. The transforming potential of the CBL mutant was
      completely abolished by the mutation of the CBL PTB domain and was decreased by
      the mutation of tyrosines 589 and 591 in the juxtamembrane domain of FLT3. A
      constitutively active AKT1 mutant (E17K) recapitulated the phenotype induced by
      the CBL deletion mutant in Ba/F3 cells. This study reveals FLT3-CBL interaction
      sites and the AKT pathway as critical mediators of transformation by oncogenic
      CBL mutants.

PMID- 23127762
TI  - Role of transcriptional corepressor ETO2 in erythroid cells.
AB  - Transcriptional corepressor ETO2 is a component of a protein complex containing
      master regulators of hematopoiesis, including GATA-1, SCL/TAL1, LMO2, and LDB1.
      To elucidate the role of ETO2 during erythroid differentiation, including the
      effects of ETO2 on GATA-1 targets, we performed gene expression profiling using
      K562 cells overexpressed with ETO2. The analysis demonstrated that 667 and 598
      genes were upregulated and downregulated (more than twofold), respectively, in
      ETO2-overexpressing cells. ETO2-repressed genes included those encoding
      prototypical erythroid proteins. To test what percentages of ETO2-repressed genes
      could be direct target genes of GATA-1 in K562 cells, we merged the microarray
      results with ChIP-seq profile (n = 5,749), demonstrating that 23.1% of ETO2
      repressed genes contained significant GATA-1 in their loci. However, there was no
      significant enrichment of PU.1 target genes among ETO2-repressed genes. Gene
      ontology analysis among ETO2-repressed genes revealed significant enrichment of
      genes related to "oxygen transporter," corresponding to globin genes.
      Quantitative chromatin immunoprecipitation and ETO2 knockdown analyses confirmed
      that ETO2 directly regulates globin genes in K562 cells. Next, we evaluated the
      role of ETO2 in human primary erythroblasts, derived from cord blood CD34
      positive cells. In an ex vivo model of erythroid differentiation from CD34
      positive cells, ETO2 protein level peaked at day 2-4 and almost diminished at the
      later stage of differentiation. Furthermore, short hairpin RNA-mediated knockdown
      and retroviral vector-mediated overexpression of ETO2 in primary erythroblasts
      suggested that ETO2 significantly represses HBB, HBA, and ALAS2 expression. In
      summary, ETO2 regulates GATA-1 target genes critical for erythroid
      differentiation, and the decrease of ETO2 levels during erythroid differentiation
      would contribute to the activation of these targets.

PMID- 23127763
TI  - The Oldowan horizon in Wonderwerk Cave (South Africa): archaeological,
      geological, paleontological and paleoclimatic evidence.

PMID- 23127764
TI  - Post-Traumatic Stress Disorders and mental health care (lessons learned from the
      Hanshin-Awaji Earthquake, Kobe, 1995).
AB  - The Hanshin-Awaji Earthquake of 1995 and has moved through the various phases
      into the recovery stage. After the earthquake we conducted two surveys involving
      approximately 8000 families with pre-school aged children and 466 families with
      disabled children. Symptoms related to PTSD were found more frequently in the
      small children whose houses had been severely damaged one year after the
      earthquake. Although the symptoms decreased, they were still present more
      frequently in the children and their mothers with severely damaged homes in 1998.
      Our results show children with intellectual or emotional disabilities displayed
      many behavioral problems. The physically disabled children required medical
      resources and specialized support in a structured environment. Both groups voiced
      the need to set up specialized facilities for people with disabilities. Following
      the Central Java Earthquake in 2006, we have engaged in "children house"
      activities in the disaster stricken area in collaboration with Gadjah Mada
      University. Through this activity, we have been able to share what works in
      helping children with disabilities and their families. From our experience we
      have found exchanging of information among the people in the disaster stricken
      areas helps to reduce the psychological damage of the children and aids in their
      recovery process.

PMID- 23127765
TI  - Colorimetric assay of matrix metalloproteinase activity based on metal-induced
      self-assembly of carboxy gold nanoparticles.
AB  - Among proteases, matrix metalloproteinases (MMPs) have been of significant
      interest because they are considered as one of the promising biomarkers in
      association with cancer metastasis, inflammation and other degenerative diseases.
      Many attempts based on the optical sensing have been made to analyze the activity
      of MMPs, but most of them require an expensive fluorescence readout and a labor
      intensive process. To circumvent this issue, we demonstrated a simple
      colorimetric detection of protease activity by using carboxy gold nanoparticles
      (AuNPs) and histidine-containing peptides via metal-affinity coordination. Due to
      their higher surface-to-volume ratio, the nanometer size of AuNPs enables the
      surface ligands to function like a chelator, providing greater affinity with
      metal ions, even in the absence of chelators. With no additional modification by
      multidentate ligands, the carboxy AuNPs were easily aggregated and changed in
      color (from reddish-brown to violet) after adding peptide substrates with
      hexahistidine at both ends and metal ions, whereas the presence of proteases in
      solution prevented NP aggregation by cleaving the peptides, thereby retaining the
      original color of the AuNPs. When the extinction ratio (E(520)/E(700)) of the
      AuNP solution was measured as a function of matrix metalloproteinase
      concentration in a single reaction, there was good linearity from as low as 3 nM
      to 52 nM. This approach is anticipated to be useful in designing other diagnostic
      nanosensors.

PMID- 23127767
TI  - Development of potential orphan drug therapy of intravesical liposomal tacrolimus
      for hemorrhagic cystitis due to increased local drug exposure.
AB  - PURPOSE: The potent immunosuppressive effect of systemic tacrolimus is limited by
      the high incidence of severe adverse effects, including nephrotoxicity and
      hypertension. Intravesical application of tacrolimus is hindered by its poor
      aqueous solubility, justifying the search for novel delivery platforms such as
      liposomes. We evaluated the pharmacokinetics of tacrolimus encapsulated in
      liposomes (lipo-tacrolimus), which is being developed as a potential orphan drug
      indication for hemorrhagic cystitis. MATERIALS AND METHODS: A single dose of lipo
      tacrolimus was instilled in the bladder with the rat under anesthesia. Also,
      tacrolimus was instilled intravesically or injected intraperitoneally in other
      rat groups. The tacrolimus dose was constant in all formulations at 200 MUg/ml.
      At different times blood, urine and bladder samples were collected and stored at 
      80C until analysis. Tacrolimus levels in samples were analyzed using
      microparticle enzyme immunoassay II. RESULTS: The AUC of lipo-tacrolimus in serum
      at 0 to 24 hours was significantly lower than that of tacrolimus instillation or
      injection. Noncompartmental pharmacokinetic data analysis revealed maximum
      concentration of lipo-tacrolimus and tacrolimus in serum and urine at 1 and at 2
      hours, respectively. Urine AUC(0-24) after intravesical administration was
      significantly higher than in the intraperitoneal group (p <0.05). Bladder
      tacrolimus AUC(0-24) did not differ significantly between the groups.
      CONCLUSIONS: Single dose pharmacokinetics revealed that bladder instillation of
      liposome encapsulated tacrolimus significantly decreased systemic exposure to
      instilled tacrolimus as well as vehicle related toxicity. Intravesical liposomal
      tacrolimus may be a promising approach as an orphan drug indication for
      hemorrhagic cystitis.

PMID- 23127766
TI  - Product related adult genitourinary injuries treated at emergency departments in
      the United States from 2002 to 2010.
AB  - PURPOSE: We describe the epidemiological features of adult genitourinary injuries
      related to consumer products and determined the patient cohorts, products and
      situations associated with increased genitourinary injury risk. MATERIALS AND
      METHODS: The National Electronic Injury Surveillance System, a data set validated
      to provide a probability sample of injury related emergency department
      presentations in the United States, was analyzed to characterize genitourinary
      injuries from 2002 to 2010. We analyzed 3,545 observations to derive national
      estimates. RESULTS: An estimated 142,144 adults (95% CI 115,324-168,964)
      presented to American emergency departments with genitourinary injuries from 2002
      to 2010. Of the injuries 69% occurred in men. A large majority of injuries
      involved the external genitalia. The most common categories of products involved
      were sporting items in 30.2% of cases, clothing articles in 9.4% and furniture in
      9.2%. The highest prevalence of injury was at ages 18 to 28 years (37.5%), which
      was most often related to sports equipment, such as bicycles. Older cohorts (age
      greater than 65 years) more commonly sustained injuries during falls and often in
      the bathroom during use of a shower or tub. Of all patients 88% were evaluated
      and treated in the emergency department without inpatient admission, although the
      admission rate increased with increasing patient age. CONCLUSIONS: Acute
      genitourinary injury is often associated with common consumer items and with
      identifiable high risk cohorts, products and situations. Consumers, practitioners
      and safety champions can use our epidemiological data to prioritize and develop
      strategies aimed at the prevention, limitation and informed treatment of such
      injuries.

PMID- 23127768
TI  - The Society of Thoracic Surgeons Isolated Aortic Valve Replacement (AVR)
      Composite Score: a report of the STS Quality Measurement Task Force.
AB  - BACKGROUND: Risk-standardized mortality rates provide a valuable but incomplete
      assessment of provider performance. Consequently, The Society of Thoracic
      Surgeons (STS) previously developed a multidimensional composite quality measure
      for coronary artery bypass grafting, the most frequently performed cardiac
      surgical procedure. The current study creates a similar composite measure for
      isolated aortic valve replacement (AVR). METHODS: Because there are few widely
      accepted process measures for AVR, the STS AVR composite score is based solely on
      outcomes, including risk-standardized mortality and any-or-none risk-standardized
      morbidity (occurrence of sternal infection, reoperation, stroke, renal failure,
      or prolonged ventilation). Isolated AVR is performed less frequently than
      coronary artery bypass grafting, and 1 year of data provided inadequate sample
      sizes for profiling. Therefore, we investigated observation periods of 3 years
      (July 1, 2007, to June 30, 2010: 67,138 records, 2,082 deaths, and 11,962
      morbidity events) and 5 years (July 1, 2005, to June 30, 2010: 101,269 records,
      3,123 deaths, and 17,514 morbidity events). We also compared results using 90%,
      95%, and 98% credible intervals, corresponding to 95%, 97.5%, and 99% Bayesian
      probabilities, to determine "star ratings." RESULTS: Differences between 3-year
      and 5-year results were small; the former was chosen because this time frame
      provides more current and relevant data. Using 3 years of data and 95% credible
      intervals, adjusted mortality and morbidity rates varied threefold from highest
      performing (3 stars) to lowest performing (1 star) programs. Approximately 3% of
      participants were 1-star, 6% were 3-star, and 91% were 2-star programs.
      CONCLUSIONS: STS has developed a composite mortality and morbidity outcomes
      measure for isolated AVR to be used in quality assessment, provider feedback,
      public reporting, and performance improvement.

PMID- 23127769
TI  - Adjuvant radiotherapy for malignant pleural mesothelioma: challenges and
      pitfalls.

PMID- 23127770
TI  - Rectal and urinary dysfunction in the TROG 03.04 RADAR trial for locally advanced
      prostate cancer.
AB  - BACKGROUND: The RADAR trial determines whether adjuvant androgen suppression,
      bisphosphonates and radiation dose escalation for localised prostate cancer (PC)
      may improve oncologic outcomes. This study examines whether these measures
      increase rectal and urinary dysfunction and are secondary trial endpoints.
      METHODS: Using a 2*2 factorial trial design men with locally advanced PC were
      randomly allocated 6 months i.m. leuprorelin prior to radiotherapy either alone
      or followed by 12 months i.m. leuprorelin. These two groups received 18 months
      i.v. zoledronic acid (Z) commencing at randomisation or no further treatment.
      Radiotherapy dose was escalated in a regulated way using external beam techniques
      (EBRT) or by a high dose rate brachytherapy (HDRB) boost. Prevalence rates of
      rectal and urinary dysfunctional symptoms were compared at baseline, the end of
      RT, 18 and 36 months according to treatment arm, dose and technique using
      multiple regression models. RESULTS: Between 2003 and 2007, 1071 men were
      randomly allocated and eligible for inclusion in this study. No persistent
      differences in rectal or urinary dysfunction were attributable to treatment arm
      or to increasing EBRT dose. However following HDRB statistical increases
      (p<0.001) in urinary dysfunction were measured using the EORTC PR25 instrument at
      18 and 36 months. CONCLUSION: Adjuvant androgen suppression, bisphosphonates and
      increasing EBRT dose did not increase rectal or urinary dysfunction in this
      trial. However dose escalation using HDRB increased urinary dysfunction.

PMID- 23127771
TI  - Scoring and classification of oropharyngeal carcinoma based on HPV-related p16
      expression.

PMID- 23127772
TI  - Proton therapy radiation pneumonitis local dose-response in esophagus cancer
      patients.
AB  - PURPOSE: This study quantifies pulmonary radiation toxicity in patients who
      received proton therapy for esophagus cancer. MATERIALS/METHODS: We
      retrospectively studied 100 esophagus cancer patients treated with proton
      therapy. The linearity of the enhanced FDG uptake vs. proton dose was evaluated
      using the Akaike Information Criterion (AIC). Pneumonitis symptoms (RP) were
      assessed using the Common Toxicity Criteria for Adverse Events version 4.0
      (CTCAEv4). The interaction of the imaging response with dosimetric parameters and
      symptoms was evaluated. RESULTS: The RP scores were: 0 grade 4/5, 7 grade 3, 20
      grade 2, 37 grade 1, and 36 grade 0. Each dosimetric parameter was significantly
      higher for the symptomatic group. The AIC winning models were 30 linear, 52
      linear quadratic, and 18 linear logarithmic. There was no significant difference
      in the linear coefficient between models. The slope of the FDG vs. proton dose
      response was 0.022 for the symptomatic and 0.012 for the asymptomatic (p=0.014).
      Combining dosimetric parameters with the slope did not improve the sensitivity or
      accuracy in identifying symptomatic cases. CONCLUSIONS: The proton radiation dose
      response on FDG PET/CT imaging exhibited a predominantly linear dose response on
      modeling. Symptomatic patients had a higher dose response slope.

PMID- 23127773
TI  - No association between TGF-beta1 polymorphisms and radiation-induced lung
      toxicity in a European cohort of lung cancer patients.
AB  - This study aimed at validating the previously published association between TGF
      beta1 single nucleotide polymorphisms and a reduced risk for radiation-induced
      lung toxicity. We were not able to confirm the reported association, neither
      using maximum dyspnea score nor after correction for baseline dyspnea score.

PMID- 23127774
TI  - Multicentre treatment planning study of MRI-guided brachytherapy for cervical
      cancer: comparison between tandem-ovoid applicator users.
AB  - BACKGROUND AND PURPOSE: To compare MRI-guided treatment planning approaches
      between four centres that use tandem-ovoid applicators. MATERIAL AND METHODS:
      Four centres generated three treatment plans for four patients: standard,
      optimised intracavitary, and optimised intracavitary/interstitial. Prescribed D90
      High-Risk CTV (HR-CTV) was 85 Gy EQD2 (external-beam radiotherapy and
      brachytherapy), while the D(2cc) OAR limit was 90 Gy EQD2 for bladder and 75 Gy
      EQD2 for rectum, sigmoid, and bowel, respectively. DVH-parameters, source loading
      patterns and spatial dose distributions of the three treatment plans were
      compared. RESULTS: The standard plans of the different centres were comparable
      with respect to the D90 HR-CTV, but differed in OAR doses. MRI-guided
      intracavitary optimisation resulted in organ sparing and smaller variation in DVH
      parameters between the centres. Adding interstitial needles led to target dose
      escalation while respecting the OAR constraints. However, substantial differences
      in relative weights of the applicator parts resulted in an increased variation in
      DVH parameters and locations of high dose regions. CONCLUSIONS: MRI-guided
      brachytherapy treatment planning optimisation provides the possibility to
      increase the dose to the HR-CTV and spare the OARs. Depending on the degree of
      conformity the centres make different choices in relative weighting of applicator
      parts, leading to different dose distributions.

PMID- 23127775
TI  - Effects of levetiracetam on seizure frequency and neuropsychological impairments
      in children with refractory epilepsy with secondary bilateral synchrony.
AB  - PURPOSE: In epilepsy with continuous spikes and waves during slow sleep (CSWS),
      which is a representative epileptic syndrome of secondary bilateral synchrony
      (SBS), the urgent suppression of this electroencephalographic (EEG) abnormality
      may be necessary to prevent the progression of neuropsychological impairments.
      The purpose of this study was to determine the efficacy of levetiracetam (LEV) on
      SBS, seizure frequency, and neuropsychological impairments in children with
      refractory epilepsy. METHODS: Eleven (seven male and four female) patients with
      refractory epilepsy with SBS on EEG, aged between 4.7 years and 11.3 years, were
      included in this study. After a 3-month baseline period, the patients were given
      LEV at an initial dose of 10mg/kg/day for the first week, followed at increments
      of 5mg/kg/day every week, up to 20mg/kg/day. The LEV dose was then adjusted up to
      a maximum of 60mg/kg/day, according to the clinician's judgment. EEG recordings
      and clinical evaluations were performed every 3 months, focusing on SBS. The
      occurrence of SBS was then scored, and the relationship between the score and the
      response to LEV treatment was evaluated. In comparison with the baseline SBS
      frequency, the EEG response to LEV treatment was classified, and responders were
      identified as having a >=50% reduction in SBS frequency. In addition, in
      comparison with the baseline seizure frequency, response to LEV treatment was
      classified. Responders were identified as patients with complete cessation (100%
      seizure control) and a response of >=50% reduction in seizures. Furthermore,
      neuropsychological impairments such as hyperactivity, impulsiveness, and
      inattention were evaluated before and after LEV treatment. RESULTS: Eight
      patients (72.7%) were considered responders. In addition, all eight patients were
      also considered responders for clinical seizures. Furthermore, 7 of 8 (87.5%)
      patients with response showed decreased hyperactivity and impulsivity after LEV
      administration. CONCLUSIONS: The present data clearly indicate the usefulness of
      LEV in reducing both SBS on EEG and seizure frequency. LEV represents an
      important addition to the treatments available for refractory childhood
      epilepsies with SBS on EEG.

PMID- 23127776
TI  - Efficacy of intravenous lacosamide as an add-on treatment in refractory status
      epilepticus: a multicentric prospective study.
AB  - OBJECTIVE: Treatment of status epilepticus (SE) has not changed in the last few
      decades, benzodiazepines plus phenytoin or valproate being the most common
      treatment. Once this first and second line treatment has failed SE is considered
      refractory (RSE). This study aimed to assess the efficacy and tolerability of
      intravenous (iv) lacosamide (LCM) in RSE. METHOD: Patients with RSE who were
      treated with ivLCM in six Spanish centers were prospectively included. Efficacy
      was defined as cessation of seizures after starting ivLCM, with no need for any
      further antiepileptic drug. All patients had been unsuccessfully treated
      following the standard protocol (benzodiazepines plus phenytoin or valproate)
      before ivLCM was added. RESULTS: Thirty-four patients were included, 52.9% men,
      with mean age of 60.15 years. In 58.9% of patients the etiology was symptomatic,
      and the most common type of SE was focal convulsive (82.4%). Mean initial bolus
      dose of LCM was 323.53mg. ivLCM was effective in more than half of patients
      (64.7%), with termination of SE before 12h in 50% of them. ivLCM was used as a
      fourth or later option in 76.5% of patients. No serious adverse events
      attributable to LCM were reported. CONCLUSIONS: LCM might be a fast, effective
      and safe add-on treatment in RSE.

PMID- 23127777
TI  - Fracture risk with use of liver enzyme inducing antiepileptic drugs in people
      with active epilepsy: cohort study using the general practice research database.
AB  - PURPOSE: Liver enzyme inducing antiepileptic drugs (LEI AEDs) have adverse
      effects on bone metabolism but it is unclear whether this translates into
      increased fracture risk. This population based cohort study aimed to evaluate
      whether treatment with LEI AEDs is associated with increased risk of fracture in
      people with active epilepsy. METHODS: The cohort included patients diagnosed with
      epilepsy and prescribed AEDs while registered at a GPRD general practice during
      1993-2008. The hazard ratio with current use of LEI AEDs for fracture at any site
      and hip fracture was estimated using Cox proportional hazards models. RESULTS:
      There were 7356 fractures (788 hip fractures) in 63259 participants. In women,
      the adjusted hazard ratio with use of LEI AEDs was 1.22 for fracture (95% CI 1.12
      1.34; p<0.001) and 1.49 for hip fracture (1.15-1.94; p=0.002). In men, the hazard
      ratio for fracture was 1.09 (0.98-1.20; p=0.123) and for hip fracture 1.53 (1.10
      2.12; p=0.011). For every 10000 women treated with LEI AEDs for one year, there
      could be 48 additional fractures, including 10 additional hip fractures. For
      every 10000 men treated with LEI AEDs for one year, there could be 4 additional
      hip fractures. CONCLUSIONS: LEI AEDs may increase the risk of fracture in people
      with epilepsy. In patients at high risk of osteoporotic fracture alternative AED
      therapy may be appropriate. Further information is urgently needed on the safety
      of valproate and newer AEDs and on strategies to maintain bone health in people
      who need to be treated with LEI.

PMID- 23127778
TI  - Serodiagnostic markers for the prediction of the outcome of intensive phase
      tuberculosis therapy.
AB  - Treatment failure and relapse may affect many tuberculosis (TB) patients who
      undergo standard anti-TB therapy. Several independent studies suggested
      unsuccessful sputum culture conversion at month 2 of treatment (slow response) as
      risk factor for treatment failure and relapse. However, earlier than month 2
      identification of patients with a high risk for poor treatment outcome would
      offer significant clinical trial and individual patient care benefits. The
      sensitivity and specificity of serological IgG and IgA responses against four
      recombinant mycobacterial antigens (ABC transporter PstS3, secreted l-alanine
      dehydrogenase, culture filtrate protein Tpx and 6 kDa early secretory antigenic
      target esxa (ESAT-6)) were evaluated separately in a blinded fashion in 21 smear
      positive pulmonary TB patient sera taken at diagnosis before commencement of
      directly observed anti-TB treatment short course comprising 13 slow responder and
      eight fast responder subjects. We observed a general pattern of higher antibody
      levels in sera of slow responders. Most pronounced were high levels of anti
      alanine dehydrogenase IgG, anti-Tpx IgG, anti-ESAT-6 IgG and anti-ESAT-6 IgA
      antibodies at diagnosis being associated with slow response with 100% specificity
      each and 46.2, 53.8, 53.8 or 53.8% sensitivity, respectively, when compared to
      fast response (P = 0.020, 0.021, 0.040 and 0.011, respectively). Discriminant
      analysis showed that the combined use of anti-Tpx IgG and anti-ESAT-6 IgA
      antibody titers before treatment predicted slow responders with 90.5% accuracy.
      These preliminary results suggest that combinations of serodiagnostic markers
      measured prior to initiation of treatment may be suitable for the prediction of
      early treatment response. This approach holds promise and requires further
      evaluation for its utility in the prediction of treatment failure and relapse,
      the evaluation of new TB therapeutics, as well as in the care of individual
      patients.

PMID- 23127779
TI  - Diagnosis of active tuberculosis by e-nose analysis of exhaled air.
AB  - Tuberculosis (TB), a highly infectious airborne disease, remains a major global
      health problem. Many of the new diagnostic techniques are not suited for
      operation in the highly-endemic low-income countries. A sensitive, fast, easy-to
      operate and low-cost method is urgently needed. We performed a Proof of Principle
      Study (30 participants) and a Validation Study (194 participants) to estimate the
      diagnostic accuracy of a sophisticated electronic nose (DiagNose, C-it BV) using
      exhaled air to detect tuberculosis. The DiagNose uses a measurement method that
      enables transfer of calibration models between devices thus eliminating the most
      common pitfall for large scale implementation of electronic noses in general.
      DiagNose measurements were validated using traditional sputum smear microscopy
      and culture on Lowenstein-Jensen media. We found a sensitivity of 95.9% and
      specificity of 98.5% for the pilot study. In the validation study we found a
      sensitivity of 93.5% and a specificity of 85.3% discriminating healthy controls
      from TB patients, and a sensitivity of 76.5% and specificity of 87.2% when
      identifying TB patient within the entire test-population (best-case numbers). The
      portability and fast time-to-result of the DiagNose enables a proactive screening
      search for new TB cases in rural areas, without the need for highly-skilled
      operators or a hospital center infrastructure.

PMID- 23127781
TI  - Effect of the embolization material in the dose calculation for stereotactic
      radiosurgery of arteriovenous malformations.
AB  - It is reported in the literature that the material used in an embolization of an
      arteriovenous malformation (AVM) can attenuate the radiation beams used in
      stereotactic radiosurgery (SRS) up to 10% to 15%. The purpose of this work is to
      assess the dosimetric impact of this attenuating material in the SRS treatment of
      embolized AVMs, using Monte Carlo simulations assuming clinical conditions. A
      commercial Monte Carlo dose calculation engine was used to recalculate the dose
      distribution of 20 AVMs previously planned with a pencil beam dose calculation
      algorithm. Dose distributions were compared using the following metrics: average,
      minimal and maximum dose of AVM, and 2D gamma index. The effect in the
      obliteration rate was investigated using radiobiological models. It was found
      that the dosimetric impact of the embolization material is less than 1.0 Gy in
      the prescription dose to the AVM for the 20 cases studied. The impact in the
      obliteration rate is less than 4.0%. There is reported evidence in the literature
      that embolized AVMs treated with SRS have low obliteration rates. This work shows
      that there are dosimetric implications that should be considered in the final
      treatment decisions for embolized AVMs.

PMID- 23127782
TI  - Role of oxygen gradients in shaping redox relationships between the human
      intestine and its microbiota.
AB  - The unique anatomy and physiology of the intestine in conjunction with its
      microbial content create the steepest oxygen gradients in the body, which plunge
      to near anoxia at the luminal midpoint. Far from static, intestinal oxygen
      gradients ebb and flow with every meal. This in turn governs the redox effectors
      nitric oxide, hydrogen sulfide, and reactive oxygen species of both host and
      bacterial origin. This review illustrates how the intestine and microbes utilize
      oxygen gradients as a backdrop for mechanistically shaping redox relationships
      and a functional coexistence.

PMID- 23127783
TI  - Leonurine (SCM-198) attenuates myocardial fibrotic response via inhibition of
      NADPH oxidase 4.
AB  - In our previous studies, we have reported that leonurine, a plant phenolic
      alkaloid in Herba leonuri, exerted cardioprotective properties in a number of
      preclinical experiments. Herein, we investigated the roles and the possible
      mechanisms of leonurine for reducing fibrotic responses in angiotensin II (Ang
      II)-stimulated primary neonatal rat cardiac fibroblasts and post-myocardial
      infarction (MI) rats. In in vitro experiments performed in neonatal rat cardiac
      fibroblasts, leonurine (10-20 MUM) pretreatment attenuated Ang II-induced
      activation of extracellular signal-regulated kinase 1/2, production of
      intracellular reactive oxygen species (ROS), expression and activity of matrix
      metalloproteinase (MMP)-2/9, and expression of alpha-smooth muscle actin and
      types I and III collagen. A small interfering RNA-mediated knockdown strategy for
      NADPH oxidase 4 (Nox4) revealed that Nox4 was required for Ang II-induced
      activation of cardiac fibroblasts. In vivo studies using a post-MI model in rats
      indicated that administration of leonurine inhibited myocardial fibrosis while
      reducing cardiac Nox4 expression, ROS production, NF-kappaB activation, and
      plasma MMP-2 activity. In conclusion, our results provide the first evidence that
      leonurine could prevent cardiac fibrosis and the activation of cardiac
      fibroblasts partly through modulation of a Nox4-ROS pathway.

PMID- 23127784
TI  - Transplantation of GABAergic cells derived from bioreactor-expanded human neural
      precursor cells restores motor and cognitive behavioral deficits in a rodent
      model of Huntington's disease.
AB  - Huntington's disease (HD) is a neurodegenerative disorder that is characterized
      by progressive dementia, choreiform involuntary movements, and emotional
      deterioration. Neuropathological features include the progressive degeneration of
      striatal gamma-aminobutyric acid (GABA) neurons. New therapeutic approaches, such
      as the transplantation of human neural precursor cells (hNPCs) to replace damaged
      or degenerated cells, are currently being investigated. The aim of this study was
      to investigate the potential for utilizing telencephalic hNPCs expanded in
      suspension bioreactors for cell restorative therapy in a rodent model of HD.
      hNPCs were expanded in a hydrodynamically controlled and homogeneous environment
      under serum-free conditions. In vitro analysis revealed that the bioreactor
      expanded telencephalic (BET)-hNPCs could be differentiated into a highly enriched
      population of GABAergic neurons. Behavioral assessments of unilateral striatal
      quinolinic acid-lesioned rodents revealed a significant improvement in motor and
      memory deficits following transplantation with GABAergic cells differentiated
      from BET-hNPCs. Immunohistochemical analysis revealed that transplanted BET-hNPCs
      retained a GABAergic neuronal phenotype without aberrant transdifferentiation or
      tumor formation, indicating that BET-hNPCs are a safe source of cells for
      transplantation. This preclinical study has important implications as the
      transplantation of GABAergic cells derived from predifferentiated BET-hNPCs may
      be a safe and feasible cell replacement strategy to promote behavioral recovery
      in HD. 

PMID- 23127785
TI  - Clinical presentation of venous thromboembolism in inflammatory bowel disease.
AB  - BACKGROUND AND AIMS: Patients with inflammatory bowel disease (IBD) are at
      increased risk of venous thromboembolism (VTE), but data on frequency, site of
      thrombosis and risk factors are limited. We sought to determine prevalence,
      incidence as well as location and clinical features of first VTE among IBD
      patients. METHODS: We evaluated a cohort of 2811 IBD patients for a history of
      symptomatic, objectively confirmed first VTE, recruited from 14 referral centers.
      Patients with VTE before IBD diagnosis or cancer were excluded. Incidence rates
      were calculated based on person-years from IBD diagnosis to first VTE or end of
      follow-up, respectively. RESULTS: 2784 patients (total observation time 24,778
      person-years) were analyzed. Overall, of 157 IBD patients with a history of VTE,
      142 (90.4%) had deep vein thrombosis (DVT) and/or pulmonary embolism (PE),
      whereas 15 (9.6%) had cerebral, portal, mesenteric, splenic or internal jugular
      vein thrombosis. The prevalence and incidence rate of all VTE was 5.6% and 6.3
      per 1000 person years, respectively. Patients with VTE were older at IBD
      diagnosis than those without VTE (34.4+/-14.8years vs 32.1+/-14.4years, p=0.045),
      but did not differ regarding sex, underlying IBD and disease duration. 121
      (77.1%) VTE were unprovoked, 122 (77.7%) occurred in outpatients and 78 (60.9%)
      in patients with active disease. Medication at first VTE included corticosteroids
      (42.3%), thiopurines (21.2%), and infliximab (0.7%). CONCLUSION: VTE is frequent
      in IBD patients. Most of them are unprovoked and occur in outpatients. DVT and PE
      are most common and unusual sites of thrombosis are rare.

PMID- 23127786
TI  - Cervical cancer screening: women's knowledge, attitudes, and practices in the
      region of Monastir (Tunisia).
AB  - BACKGROUND: In Tunisia, cervical cancer is considered the second leading cancer
      in women and causes high morbidity and mortality. This study aimed to investigate
      women's knowledge, attitudes, and practices of cervical cancer screening in the
      region of Monastir (Tunisia). METHODS: We conducted a cross-sectional study
      exploring the cervical cancer screening knowledge, attitudes, and practices of
      women in the region of Monastir. The study was conducted in health centers in
      this region from 1st March to 30th June 2009. Data were collected using a
      structured questionnaire containing 15 items on demographic status, knowledge of
      risk factors and screening methods, and attitudes toward the relevance and
      effectiveness of cervical cancer screening. RESULTS: A total of 900 women agreed
      to take part in the study. Their mean age was 41.6+/-12.4 years and 64% did not
      exceed the primary level of education. According to the constructed scores, 22.8%
      of the participants had good knowledge of cervical cancer risk factors and 38.2%
      had good knowledge of screening methods. Multiple logistic regression analysis
      showed that women aged 45 and older, married, with good knowledge of risk factors
      and screening methods were more likely to undergo cervical cancer screening (P
      value<0.01). CONCLUSION: This study provides useful information that could be
      utilized by both researchers and those involved in public health programs. The
      results show the need for educational programs to enhance women's adherence to
      cervical cancer screening programs in Tunisia.

PMID- 23127788
TI  - A theoretical study on mathematical modelling of an infectious disease with
      application of optimal control.
AB  - In this paper, we propose and analyze an epidemic problem which can be controlled
      by vaccination as well as treatment. In the first part of our analysis we study
      the dynamical behavior of the system with fixed control for both vaccination and
      treatment. Basic reproduction number is obtained in all possible cases and it is
      observed that the simultaneous use of vaccination and treatment control is the
      most favorable case to prevent the disease from being epidemic. In the second
      part, we take the controls as time dependent and obtain the optimal control
      strategy to minimize both the infected populations and the associated costs. All
      the analytical results are verified by simulation works. Some important
      conclusions are given at the end of the paper.

PMID- 23127787
TI  - Developmental biomechanics of neck musculature.
AB  - Neck mechanics is central to head injury prevention since it is the
      musculoskeletal neck, which dictates the position and movement of the head. In
      the US, traumatic injury is the leading cause of death for children; however
      prevention is hampered by the lack of data concerning the mechanics of the
      immature head-and-neck. Thus, the objective of this study was to quantify neck
      muscle strength and endurance across the maturation spectrum and correlate these
      with head-and-neck anthropometry. A factorial study was performed on 91 human
      subjects measuring head-and-neck anthropometry and neck strength and endurance in
      three bending directions (flexion, extension, and lateral) as a function of age
      (6-23 years). Using a custom device, neck maximum voluntary contraction (MVC)
      force was measured in triplicate. Next, neck muscle endurance (sustained effort)
      was measured as the subjects' ability to maintain 70% of peak force over 30s.
      Linear regression of peak force and endurance as a function of age revealed each
      direction to significantly (p<0.0001) increase with age. The MVC force, averaged
      across all directions and normalized to the adult values, exhibits the following
      maturation curve: %MVC Force=-0.0879(age)(2)+6.018(age)+8.120. Neck muscle
      strength, similar between young males and females, becomes disparate in
      adolescence and adulthood with males exhibiting greater strength. Bending
      direction differences were also found with extension strength being the greatest
      regardless of age and sex. Furthermore, neck circumference appears predictive of
      neck strength and endurance in children. Together, these relationships may
      facilitate improved design of injury prevention interventions.

PMID- 23127789
TI  - Quantum-like model of behavioral response computation using neural oscillators.
AB  - In this paper we propose the use of neural interference as the origin of quantum
      like effects in the brain. We do so by using a neural oscillator model consistent
      with neurophysiological data. The model used was shown elsewhere to reproduce
      well the predictions of behavioral stimulus-response theory. The quantum-like
      effects are brought about by the spreading activation of incompatible
      oscillators, leading to an interference-like effect mediated by inhibitory and
      excitatory synapses.

PMID- 23127790
TI  - Quality of intraoperatively salvaged unwashed blood in hip arthroplasty.
AB  - BACKGROUND AND OBJECTIVES: Transfusion of autologous whole blood is one available
      method to reduce the need for allogenic blood transfusion. The aim of the present
      study was to investigate the quality of shed blood collected in a new
      intraoperative autotransfusion system. MATERIALS AND METHODS: In this prospective
      study fifteen consecutive patients who were scheduled for elective total hip
      arthroplasty were included. Shed blood was collected with a novel intraoperative
      autologous blood transfusion system (Sangvia(r), AstraTech) from the surgical
      wound. Blood samples were taken from the transfusion bag. RESULTS: Mean blood
      loss during operation was 364ml (190-750ml) and mean transfused blood volume was
      200ml (30-700ml). Mean haemoglobin concentration was 62g/l (17-91g/l) and mean
      plasma free haemoglobin concentration was 6.7g/l (1.9-12.7g/l) in transfusion
      blood. CONCLUSION: The basic laboratory characteristics of intraoperatively
      salvaged blood with the Sangvia(r) system are generally in the same range as
      reported in the studies on the postoperative transfusion of unwashed blood. From
      a blood quality point of view, our study indicates that transfusion of
      intraoperatively salvaged unwashed blood with the Sangvia(r) system in patients
      undergoing total hip arthroplasty is expected to be safe.

PMID- 23127791
TI  - Increasing reporting of adverse events to improve the educational value of the
      morbidity and mortality conference.
AB  - BACKGROUND: The aim of this study was to investigate the impact of a validated
      complication proforma on surgical Morbidity and Mortality (M&M) conference
      reporting. STUDY DESIGN: The ACS-NSQIP (American College of Surgeons-National
      Surgical Quality Improvement Program) 30-day complication proforma, when
      implemented, previously showed a 25% increase in morbidity and a 50% increase in
      mortality reporting. A pilot study introducing the paper-based proforma was
      undertaken, collecting prospective M&M data for 2,094 of 2,209 colorectal, upper
      gastrointestinal, breast, and vascular inpatients (94.7% compliance). A
      comparative analysis using the proforma vs traditional M&M data collection was
      used to compare accuracy of M&M data reporting. RESULTS: There was a 73% increase
      in morbidities reported using the proforma as compared with M&M reporting (547 vs
      316), and an increase of 10.81% (37 vs 41) in the reporting of mortalities. Of
      those patients with morbidities (n = 278), 70.24% (n = 203) had at least 1
      surgical intervention. The median length of stay in patients with morbidities was
      12 vs 3 days in those with no morbidities. CONCLUSIONS: We demonstrated that
      prospective standardized incident recording provides significantly more accurate
      assessment of M&M data compared with current reporting methods. This increased
      accuracy should favorably affect surgical performance indicators and casemix
      funding.

PMID- 23127792
TI  - Recognizing residents with a deficiency in operative performance as a step closer
      to effective remediation.

PMID- 23127793
TI  - Colorectal surgery surgical site infection reduction program: a national surgical
      quality improvement program--driven multidisciplinary single-institution
      experience.
AB  - BACKGROUND: Surgical site infections (SSI) are a major cause of morbidity in
      surgical patients and they increase health care costs considerably. Colorectal
      surgery is consistently associated with high SSI rates. No single intervention
      has demonstrated efficacy in reducing colorectal SSIs. The American College of
      Surgeons National Surgical Quality Improvement Program (ACS NSQIP) is a
      nationally validated system that uses clinically abstracted data on surgical
      patients and their outcomes to assist participating institutions drive quality
      improvement. STUDY DESIGN: A multidisciplinary team was assembled to develop a
      colorectal SSI-reduction bundle at an academic tertiary care medical center. The
      ACS NSQIP data were used to identify patterns of SSIs during a 2-year period.
      Multiple interventions across the entire surgical episode of care were developed
      and implemented in January 2011. Monthly ACS NSQIP data were used to track
      progress. RESULTS: Our ACS NSQIP overall colorectal SSI rate for 2009 and 2010
      was 9.8%. One year after implementation of the SSI reduction bundle, we
      demonstrated a significant decline (p < 0.05) in both overall and superficial
      SSIs, to 4.0% and 1.5%, respectively. Organ space infections declined to 2.6%,
      which was not a significant change (p = 0.10). During the entire analysis period
      (2009 to 2011), there was no change in our colorectal-specific Surgical Care
      Improvement Program performance. CONCLUSIONS: Using our ACS NSQIP colorectal SSI
      outcomes, a multidisciplinary team designed a colorectal SSI reduction bundle
      that resulted in a substantial and sustained reduction in SSIs. Our study is not
      able to identify which specific elements contributed to the reduction.

PMID- 23127794
TI  - Aberrant alternative splicing events in Parkinson's disease.
AB  - Alternative splicing (AS) using a sole gene to express multiple transcripts with
      diverse protein coding sequences and/or RNA regulatory elements raises genomic
      complexities. In the nervous system, several thousand AS events play important
      roles in ion transportation, receptor recognition, neurotransmission, memory, and
      learning. Not surprisingly, AS influences human physiology, development, and
      disease. Many research studies have focused on aberrant AS in nervous system
      diseases, including Parkinson's disease (PD), the second most common progressive
      neurodegenerative disorder of the central nervous system. PD affects the lives of
      several million people globally. It is caused by protein aggregation, such as in
      Lewy bodies, and the loss of dopaminecontaining neurons in the substantia nigra
      of the midbrain. To our knowledge, six genes, including PARK2, SNCAIP, LRRK2,
      SNCA, SRRM2, and MAPT, are involved in aberrant AS events in PD patients. In this
      review, we highlight the relevance of aberrant AS in PD and discuss the use of an
      aberrant AS profile as a potential diagnostic or prognostic marker for PD and as
      a possible means of applying therapy. 

PMID- 23127795
TI  - Non-linguistic learning and aphasia: evidence from a paired associate and
      feedback-based task.
AB  - Though aphasia is primarily characterized by impairments in the comprehension
      and/or expression of language, research has shown that patients with aphasia also
      show deficits in cognitive-linguistic domains such as attention, executive
      function, concept knowledge and memory. Research in aphasia suggests that
      cognitive impairments can impact the online construction of language, new verbal
      learning, and transactional success. In our research, we extend this hypothesis
      to suggest that general cognitive deficits influence progress with therapy. The
      aim of our study is to explore learning, a cognitive process that is integral to
      relearning language, yet underexplored in the field of aphasia rehabilitation. We
      examine non-linguistic category learning in patients with aphasia (n=19) and in
      healthy controls (n=12), comparing feedback and non-feedback based instruction.
      Participants complete two computer-based learning tasks that require them to
      categorize novel animals based on the percentage of features shared with one of
      two prototypes. As hypothesized, healthy controls showed successful category
      learning following both methods of instruction. In contrast, only 60% of our
      patient population demonstrated successful non-linguistic category learning.
      Patient performance was not predictable by standardized measures of cognitive
      ability. Results suggest that general learning is affected in aphasia and is a
      unique, important factor to consider in the field of aphasia rehabilitation.

PMID- 23127796
TI  - Prefrontal cortex contributions to controlled memory judgment: fMRI evidence from
      adolescents and young adults.
AB  - Cortical regions supporting cognitive control and memory judgment are
      structurally immature in adolescents. Here we studied adolescents (13-15 y.o.)
      and young adults (20-22 y.o.) using a recognition memory paradigm that modulates
      cognitive control demands through cues that probabilistically forecast memory
      probe status. Behaviorally, adolescence was associated with quicker responding in
      the presence of invalid cues compared to young adulthood. fMRI data demonstrated
      that while both groups increasingly activated posterior dorsolateral prefrontal
      (dlPFC), midline, and lateral parietal regions for invalidly compared to validly
      cued trials, this differential invalid cueing response ended sooner in
      adolescents, consistent with their quicker responding on invalidly cued trials.
      Critically, dlPFC also demonstrated reversed brain-behavior associations across
      the groups. Increased mean dlPFC activation during invalid cueing was linked to
      improved performance in young adults, whereas increases within adolescents were
      linked to impaired performance. Resting state connectivity analysis revealed
      greater connectivity between dlPFC and episodic retrieval linked regions in young
      adults relative to adolescents. These data demonstrate that the functional
      interpretation of dlPFC activation hinges on its physical maturation and suggest
      that the pattern of behavioral and neural response in adolescents reflects
      different functional integration of cognitive control and memory systems.

PMID- 23127797
TI  - The cellular function of srGAP3 and its role in neuronal morphogenesis.
AB  - The Slit-Robo GTPase activating protein 3 (srGAP3) dynamically regulates
      cytoskeletal reorganisation through inhibition of the Rho GTPase Rac1 and
      interaction with actin remodelling proteins. SrGAP3-mediated reorganisation of
      the actin cytoskeleton is crucial for the normal development of dendritic spines
      and loss of srGAP3 leads to abnormal synaptic activity and impaired cognitive
      behaviours in mice, which is reminiscent of an association between disrupted
      srGAP3 and intellectual disability in humans. Additionally, srGAP3 has been
      implicated to act downstream of Slit-Robo signalling in commissural axons of the
      spinal cord. Thus, srGAP3-mediated cytoskeletal reorganisation has an important
      influence on a variety of neurodevelopmental processes, which may be required for
      normal cognitive function.

PMID- 23127798
TI  - Healthcare-seeking prevalence of lower urinary tract symptoms among national
      health insurance enrollees in Taiwan, 2000-2009.
AB  - OBJECTIVE: To investigate the healthcare-seeking prevalence of those with lower
      urinary tract symptoms (LUTS) among National Health Insurance enrollees in
      Taiwan. MATERIALS AND METHODS: Data from the National Health Insurance Research
      Database were obtained from a random population sample of about one million as a
      representative cohort from 2000 to 2009. Subjects aged>=18 years with >=1
      outpatient service claim and coding for a LUTS-related diagnosis were identified
      and analyzed annually. RESULTS: The healthcare-seeking prevalence for LUTS
      increased from 23.110/00 in 2000 to 38.370/00 in 2009. Similar trends were found
      for storage symptoms and voiding symptoms (P<.0001). In 2009, the age
      distribution of LUTS was 4.32%, 5.82%, 10.92%, 19.23%, 21.25%, and 38.47% in
      those aged 18-29, 30-39, 40-49, 50-59, 60-69, and >=70 years, respectively. The
      overall LUTS prevalence was more common in men (54.450/00) than in women
      (21.730/00). For LUTS subtypes, storage symptoms were more common in women
      (19.460/00) than in men (13.130/00); however, the trend was reversed in the
      population>60 years old. Voiding and mixed symptoms were more common in men
      (4.690/00, and 0.830/00, respectively) than in women (2.800/00 and 0.580/00,
      respectively). CONCLUSION: In the present cohort study, patients with LUTS
      seeking medical help increased annually from 2000 to 2009 in Taiwan. The
      occurrence of LUTS subtypes varied according to age and sex. LUTS is becoming a
      substantial healthcare burden as the number of aged people who want to maintain a
      good quality of life increases.

PMID- 23127799
TI  - Characterization of fibrinogen-like protein 2 (FGL2): monomeric FGL2 has enhanced
      immunosuppressive activity in comparison to oligomeric FGL2.
AB  - Fibrinogen-like protein 2 (FGL2), a novel effector molecule of
      CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg), mediates its suppressive
      activity through binding to low affinity Fcgamma receptors expressed on antigen
      presenting cells (APCs). FGL2 has been implicated in the pathogenesis of viral
      hepatitis, xeno- and allotransplant rejection, and rheumatoid arthritis. Here we
      fully analyzed the structure-function relationships of recombinant murine FGL2
      generated in COS-7 cells and identified the receptor binding domains. Native FGL2
      exists as an oligomer with a molecular weight of approximately 260 kDa, while
      under reducing conditions, FGL2 has a molecular weight of 65 kDa suggesting that
      native FGL2 is composed of four monomers. By site-directed mutation, cysteines at
      positions 94, 97, 184 and 187, found in the coiled-coil domain were shown to be
      crucial for FGL2 oligomerization. Monomeric FGL2 had a lower affinity binding to
      APCs, but increased immunosuppressive activity compared to oligomeric FGL2.
      Deglycosylation demonstrated that sugar moieties are critical for maintaining
      solubility of FGL2. SWISS-MODEL analysis suggested that FGL2 has a similar
      tertiary structure with other members of the fibrinogen family such as fibrinogen
      and tachylectin. Mutational analysis of cysteine residues and Western blots
      suggested an asymmetric bouquet-shaped quaternary structure for oligomeric FGL2,
      resembling many pattern-recognition molecules in the lectin pathway of innate
      immunity. The functional motifs of FGL2 were mapped to the C terminal globular
      domain, using a peptide blockade assay. These results collectively define the
      biochemical and immunological determinants of FGL2, an important
      immunosuppressive molecule of Treg providing important insights for designing
      FGL2-related therapeutics.

PMID- 23127800
TI  - Live-cell imaging of endogenous Ras-GTP shows predominant Ras activation at the
      plasma membrane and in the nucleus in Saccharomyces cerevisiae.
AB  - Ras proteins function as a point of convergence for different signalling pathways
      in eukaryotes and are involved in many cellular responses; their different
      subcellular locations could regulate distinct functions. To investigate the
      localization of active Ras in vivo in Saccharomyces cerevisiae, we expressed a
      probe consisting of a GFP fusion with a trimeric Ras binding domain of Raf1 (eGFP
      RBD3), which binds Ras-GTP with a much higher affinity than Ras-GDP. Our results
      show that in wild type cells active Ras accumulates mainly at the plasma membrane
      and in the nucleus during growth on medium containing glucose, while it
      accumulates mainly in mitochondria in wild type glucose-starved cells and
      relocalizes to the plasma membrane and to the nucleus upon addition of this
      sugar. A similar pattern is observed in a strain deleted in the CYR1 gene
      indicating that the absence of adenylate cyclase does not impair the localization
      of Ras-GTP. Remarkably, in a gpa2Delta, but not in a gpr1Delta mutant, active Ras
      accumulates in internal membranes and mitochondria, both when cells are growing
      on glucose medium or are starved, indicating that Gpa2, but not Gpr1 is required
      for the recruitment of Ras-GTP at the plasma membrane and in the nucleus.
      Moreover, deletion of both HXK1 and HXK2 also causes a mitochondrial localization
      of the probe, which relocalizes to the plasma membrane and to the nucleus upon
      expression of HXK2 on a centromeric plasmid, suggesting that this kinase is
      involved in the proper localization of active Ras.

PMID- 23127801
TI  - Curcumin ameliorates diabetic nephropathy by inhibiting the activation of the
      SphK1-S1P signaling pathway.
AB  - Curcumin, a major polyphenol from the golden spice Curcuma longa commonly known
      as turmeric, has been recently discovered to have renoprotective effects on
      diabetic nephropathy (DN). However, the mechanisms underlying these effects
      remain unclear. We previously demonstrated that the sphingosine kinase 1
      sphingosine 1-phosphate (SphK1-S1P) signaling pathway plays a pivotal role in the
      pathogenesis of DN. This study aims to investigate whether the renoprotective
      effects of curcumin on DN are associated with its inhibitory effects on the SphK1
      S1P signaling pathway. Our results demonstrated that the expression and activity
      of SphK1 and the production of S1P were significantly down-regulated by curcumin
      in diabetic rat kidneys and glomerular mesangial cells (GMCs) exposed to high
      glucose (HG). Simultaneously, SphK1-S1P-mediated fibronectin (FN) and
      transforming growth factor-beta 1 (TGF-beta1) overproduction were inhibited. In
      addition, curcumin dose dependently reduced SphK1 expression and activity in GMCs
      transfected with SphK(WT) and significantly suppressed the increase in SphK1
      mediated FN levels. Furthermore, curcumin inhibited the DNA-binding activity of
      activator protein 1 (AP-1), and c-Jun small interference RNA (c-Jun-siRNA)
      reversed the HG-induced up-regulation of SphK1. These findings suggested that
      down-regulation of the SphK1-S1P pathway is probably a novel mechanism by which
      curcumin improves the progression of DN. Inhibiting AP-1 activation is one of the
      therapeutic targets of curcumin to modulate the SphK1-S1P signaling pathway,
      thereby preventing diabetic renal fibrosis.

PMID- 23127802
TI  - Molecular cloning and characterization of the corticoid receptors from the
      American alligator.
AB  - Steroid hormones are essential for health in vertebrates. Corticosteroids, for
      example, have a regulatory role in many physiological functions, such as
      osmoregulation, respiration, immune responses, stress responses, reproduction,
      growth, and metabolism. Although extensively studied in mammals and some non
      mammalian species, the molecular mechanisms of corticosteroid hormone
      (glucocorticoids and mineralocorticoids) action are poorly understood in
      reptiles. Here, we have evaluated hormone receptor-ligand interactions in the
      American alligator (Alligator mississippiensis), following the isolation of cDNAs
      encoding a glucocorticoid receptor (GR) and a mineralocorticoid receptor (MR).
      The full-length alligator GR (aGR) and aMR cDNAs were obtained using 5' and 3'
      rapid amplification cDNA ends (RACE). The deduced amino acid sequences exhibited
      high identity to the chicken orthologs (aGR: 83%; aMR: 90%). Using transient
      transfection assays of mammalian cells, both aGR and aMR proteins displayed
      corticosteroid-dependent activation of transcription from keto-steroid hormone
      responsive, murine mammary tumor virus promoters. We further compared the ligand
      specifity of human, chicken, Xenopus, and zebrafish GR and MR. We found that the
      alligator and chicken GR/MR have very similar amino acid sequences, and this
      translates to very similar ligand specificity. This is the first report of the
      full-coding regions of a reptilian GR and MR, and the examination of their
      transactivation by steroid hormones.

PMID- 23127803
TI  - Repetitive transarterial chemoembolization (TACE) of liver metastases from
      gastric cancer: local control and survival results.
AB  - OBJECTIVE: To evaluate the local tumor control and survival data after
      transarterial chemoembolization with different drug combinations in the
      palliative treatment of patients with liver metastases of gastric cancer.
      MATERIALS AND METHODS: The study was retrospectively performed. 56 patients (mean
      age, 52.4) with unresectable liver metastases of gastric cancer who did not
      respond to systemic chemotherapy were repeatedly treated with TACE in 4-week
      intervals. In total, 310 chemoembolization procedures were performed (mean, 5.5
      sessions per patient). The local chemotherapy protocol consisted of mitomycin
      alone (30.4%), mitomycin and gemcitabine (33.9%), or mitomycin, gemcitabine and
      cisplatin (35.7%). Embolization was performed with lipiodol and starch
      microspheres. Local tumor response was evaluated by MRI according to RECIST.
      Survival data from first chemoembolization were calculated according to the
      Kaplan-Meier method. RESULTS: The local tumor control was: complete response in
      1.8% (n=1), partial response in 1.8% (n=1), stable disease in 51.8% (n=29) and
      progressive disease in 44.6% (n=25) of patients. The 1-, 2-, and 3-year survival
      rate from the start of chemoembolization were 58%, 38%, and 23% respectively. The
      median and mean survival times were 13 and 27.1 months. A Statistically
      significant difference between patients treated with different chemotherapy
      protocols was noted (rho=0.045) with the best survival time in the mitomycin,
      gemcitabine and cisplatin group. CONCLUSION: Transarterial chemoembolization is a
      minimally invasive therapy option for palliative treatment of liver metastases in
      patients with gastric cancer.

PMID- 23127804
TI  - Perfusion CT can predict tumoral grading of pancreatic adenocarcinoma.
AB  - OBJECTIVES: To describe perfusion CT features of locally advanced pancreatic
      ductal adenocarcinoma and to evaluate correlation with tumor grading. METHODS:
      Thirty-two patients with locally advanced pancreatic adenocarcinoma were included
      in this study. Lesions were evaluated by P-CT and biopsy after patient's informed
      consent. P-CT parameters have been assessed on a large single and on 6 small
      intratumoral ROIs. Values obtained have been compared and related to the tumor
      grading using Mann-Whitney U test. Sensibility, specificity, positive predictive
      value (PPV), negative predictive value (NPV) and accuracy in predicting tumor
      grading have been calculated for cut-off values chosen by using ROC curves.
      RESULTS: Out of 32 lesions, 12 were classified as low grade and 20 as high grade.
      A statistically significant difference between high and low grade neoplasms were
      demonstrated for PEI and BV parameters. PEI and BV cut-off values were
      respectively 17.8 HU and 14.8 ml/100g. PEI identified high grade neoplasms with a
      65% sensitivity, 92% specificity, 93% PPV, 61% NPV and 75% accuracy. BV
      identified high grade neoplasms with a 80% sensitivity, 75% specificity, 84% PPV,
      69% NPV, 78% accuracy. Considering both PEI and BV, P-CT identified high grade
      lesions with a 60% sensitivity, 100% specificity, 100% PPV, 60% NPV and 75%
      accuracy. CONCLUSIONS: PEI and BV perfusion CT parameters proved their efficiency
      in identifying high grade pancreatic adenocarcinoma.

PMID- 23127805
TI  - Widely applicable coinage metal window electrodes on flexible polyester
      substrates applied to organic photovoltaics.
AB  - The fabrication, exceptional properties, and application of 8 nm thick Cu, Ag,
      Au, and Cu/Ag bilayer electrodes on flexible polyethylene terephthalate (PET) and
      polyethylene naphthalate (PEN) substrates is reported. These electrodes are
      fabricated using a solvent free process in which the plastic surface is
      chemically modified with a molecular monolayer of thiol and amine terminated
      alkylsilanes prior to metal deposition. The resulting electrodes have a sheet
      resistance of <=14 Omega sq-1, are exceptionally robust and can be rapidly
      thermally annealed at 200  degrees C to reduce their sheet resistance to <=9
      Omega sq-1. Notably, annealing Au electrodes briefly at 200  degrees C causes the
      surface to revert almost entirely to the {111} face, rendering it ideal as a
      model electrode for fundamental science and practical application alike. The
      power conversion efficiency of 1 cm2 organic photovoltaics (OPVs) employing 8 nm
      Ag and Au films as the hole-extracting window electrode exhibit performance
      comparable to those on indium-tin oxide, with the advantage that they are
      resistant to repeated bending through a small radius of curvature and are
      chemically well-defined. OPVs employing Cu and bilayer Cu:Ag electrodes exhibit
      inferior performance due to a lower open-circuit voltage and fill factor.
      Measurements of the interfacial energetics made using the Kelvin probe technique
      provide insight into the physical reason for this difference. The results show
      how coinage metal electrodes offer a viable alternative to ITO on flexible
      substrates for OPVs and highlight the challenges associated with the use of Cu as
      an electrode material in this context.

PMID- 23127806
TI  - Randomized, double-blind, placebo-controlled trial of polyethylene glycol
      (MiraLAX(r)) for urinary urge symptoms.
AB  - OBJECTIVE: Polyethylene glycol (PEG) is common first-line therapy for urinary
      symptoms despite minimal evidence-based support. We performed a randomized,
      double-blind, placebo-controlled study of PEG for initial treatment of overactive
      bladder (OAB) symptoms in children. PATIENTS AND METHODS: Patients aged >3 years
      underwent baseline urinary symptom questionnaire (USQ, scored 0-16), bowel
      symptom questionnaire (scored 0-20) and abdominal X-ray (KUB). Patients were
      randomized to placebo/PEG regardless of parent's perception of constipation.
      After 1 month, patients completed follow-up questionnaires and KUB. Improvement
      was defined as decrease in USQ (DeltaUSQ) >= 3 points. Secondary analyses
      compared urinary and bowel symptoms to KUB. RESULTS: Of 138 enrolled patients, 71
      (51.4%) completed 1 month of therapy. Analyses of those randomized to placebo vs.
      PEG and non-completers demonstrated similar demographics, baseline symptoms, and
      KUB. Patients treated with placebo and PEG both had significant improvement in
      USQ scores (p < 0.0001). Patients treated with placebo and PEG responded
      similarly to placebo (DeltaUSQ 3.7 vs. 3.4, p = 0.773), with improvement in
      nearly half (48.5% PEG vs. 44.7% placebo). There was no correlation between KUB
      and urinary or bowel symptoms. CONCLUSIONS: Nearly 50% of patients with urinary
      urge symptoms treated with either placebo or PEG for 1 month had improvement in
      urinary symptoms. KUB did not correlate with baseline or follow-up urinary or
      bowel symptoms.

PMID- 23127807
TI  - Influence of particle properties on the wall region in packed capillaries.
AB  - Analytical columns (4.6 mm i.d.) packed with core-shell particles have shown a
      significantly reduced eddy dispersion contribution to band broadening compared to
      conventional fully porous particles. It has been speculated if this is caused by
      the narrow particle size distribution (PSD) of the core-shell particles, as an
      intrinsic advantage, or by an improved packing structure that specifically
      reduces the transcolumn velocity biases caused by wall effects. A recent
      simulation study has pointed against the former proposition [A. Daneyko et al.,
      Anal. Chem. 83 (2011) 3903]. It is more likely that the slurry packing process
      for core-shell particles results in bed morphologies with reduced wall effects
      compared to the fully porous particles with a wide PSD. To access the latter
      proposition experimentally we slurry packed capillary columns (100 MUm i.d.) with
      different fully porous (wide PSDs) and core-shell (narrow PSDs) particles and
      imaged their bed structures three-dimensionally using confocal laser scanning
      microscopy. This allowed us to resolve and analyze the bed morphology in these
      columns locally on all length scales contributing to eddy dispersion. On the
      transcolumn scale we observed a systematic difference between core-shell and
      fully porous particles: In the vicinity of the column wall the core-shell
      particles packed denser (closer to the bulk packing densities) and with a higher
      regularity than the fully porous particles. The bulk regions of all packings were
      effectively indistinguishable. This provides experimental evidence that the
      reduced eddy dispersion contribution with core-shell packings should be
      attributed to a higher transcolumn homogeneity rather than to an improved bed
      morphology on smaller length scales, e.g., to a reduced short-range disorder.

PMID- 23127808
TI  - Journal of Chromatography A. Capillary electromigration techniques. Foreword.

PMID- 23127809
TI  - Human serum albumin-coated gold nanoparticles for selective extraction of
      lysozyme from real-world samples prior to capillary electrophoresis.
AB  - This study describes the use of human serum albumin (HSA)-modified gold
      nanoparticles (HSA-AuNPs) for the selective extraction and enrichment of high-pI
      protein, lysozyme (Lyz) prior to analysis by capillary electrophoresis (CE) with
      UV detection. HSA-AuNPs are capable of extracting Lyz from a complex matrix
      because a HSA capping layer not only stabilizes gold nanoparticles in a high-salt
      environment but also exhibits strong electrostatic attraction with Lyz under
      neutral pH condition. Efficient separation of Lyz and other high-pI proteins has
      been successfully achieved by the filling of cationic polyelectrolyte,
      poly(diallydimethylammonium chloride) (PDDAC), to the background electrolyte.
      After capturing Lyz with HSA-AuNPs, PDDAC-filled CE can be directly used for the
      analysis of the extracted Lyz without the addition of the releasing agent into
      the extractor. The extraction efficiency relied on the pH of the solution and the
      concentration of HSA-AuNPs. Under optimal extraction conditions, the limit of
      detection at a signal-to-noise ratio of 3 for Lyz was down to 8 nM. The
      combination of HSA-AuNP extraction and PDDAC-filled CE has been applied the
      analyses of Lyz in hen egg white, human milk, and human tear. Also, this NP-based
      extraction can be coupled to matrix-assisted desorption/ionization time-of-flight
      mass spectrometry and sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

PMID- 23127810
TI  - Pesticide analysis in teas and chamomile by liquid chromatography and gas
      chromatography tandem mass spectrometry using a modified QuEChERS method:
      validation and pilot survey in real samples.
AB  - This paper presents the validation of a modified QuEChERS method in four matrices
      - green tea, red tea, black tea and chamomile. The experiments were carried out
      using blank samples spiked with a solution of 86 pesticides (insecticides,
      fungicides and herbicides) at four levels - 10, 25, 50 and 100 MUg/kg. The
      samples were extracted according to the citrate QuEChERS protocol; however, to
      reduce the amount of coextracted matrix compounds, calcium chloride was employed
      instead of magnesium sulphate in the clean-up step. The samples were analysed by
      LC-MS/MS and GC-MS/MS. Included in the scope of validation were: recovery,
      linearity, matrix effects, limits of detection and quantitation as well as intra
      day and inter-day precision. The validated method was used in a real sample
      survey carried out on 75 samples purchased in ten different countries. In all
      matrices, recoveries of the majority of compounds were in the 70-120% range and
      were characterised by precision lower than 20%. In 85% of pesticide/matrix
      combinations the analytes can be detected quantitatively by the proposed method
      at the European Union Maximum Residue Level. The analysis of the real samples
      revealed that large number of teas and chamomiles sold in the European Union
      contain pesticides whose usage is not approved and also pesticides in
      concentrations above the EU MRLs.

PMID- 23127811
TI  - Novel double-confined polymeric ionic liquids as sorbents for solid-phase
      microextraction with enhanced stability and durability in high-ionic-strength
      solution.
AB  - Because of the occurrence of ion exchange between high-ionic-strength solution
      and anions of polymeric ionic liquids (PILs), PILs based solid-phase
      microextraction (SPME) fibers were rarely used in direct immersion mode to high
      salt-added samples. In this work, a novel double-confined PIL sorbent was
      prepared by co-polymerization of cation and anion of 1-vinyl-3-octylimidzaolium p
      styrenesulfonate (VOIm(+)SS(-)). The poly(VOIm(+)-SS(-)) was chemically bonded
      onto functionalized stainless steel wire via surface radical chain-transfer
      reaction. Stability of poly(VOIm(+)-SS(-)) in high-ionic-strength solution was
      investigated and compared with that of poly(1-vinyl-3-octylimidzaolium
      benzenesulfonate) (poly(VOIm(+)BS(-))) by elemental analysis of sulfur element,
      and results turned out that the poly(VOIm(+)-SS(-)) was more stable. Coupled to
      gas chromatography (GC), the poly(VOIm(+)-SS(-)) fiber was used to extract three
      sorts of compounds including anilines, phenols and phthalate esters in aqueous
      solution. The as-established method showed good linearity, low detection limits,
      and acceptable repeatability. The direct immersion SPME-GC method was applied to
      determine the model phthalate esters in bottled mineral water. The determination
      results were satisfactory.

PMID- 23127812
TI  - A practical method for the quantitative assessment of non-enantioselective versus
      enantioselective interactions encountered in liquid chromatography on brush-type
      chiral stationary phase.
AB  - A convenient experimental method for the quantitative assessment of
      enantioselective versus non-enantioselective interactions in liquid
      chromatography on brush-type chiral stationary phases (CSPs) is described. This
      procedure involves the systematic evaluation of the retention characteristics of
      resolved enantiomers as chiral selectands, SAs, on a set of CSPs containing
      chiral selectors, SOs, attached to an achiral support S with well-defined but
      different surface SO loading levels. The emerging body of retention data can be
      dissected into non-enantioselective and enantioselective increments by equations
      accounting separately for the two co-existing equilibrium processes, namely the
      "unproductive" adsorption of the enantiomers on the achiral domains of the CSP
      and their "productive" enantioselective association with the surface-anchored
      chiral SOs. The general applicability of this approach was demonstrated using a
      set of CSPs loaded with different densities of a quinine carbamate anion exchange
      type SO, and three acidic model SAs, i.e., N-Fmoc-phenylalanine, N-[(3,5
      dipropoxybenzyloxy)carbonyl]leucine and 2-(2,4-dichlorophenoxy)propanoic acid,
      employing nonpolar, polar organic and reversed phase mobile phase conditions. In
      all tested mobile phase environments, the global retention characteristics of the
      studied SO was found to be dominated by enantioselective SA/SO binding rather
      than by non-enantioselective SA/support interactions, providing evidence for
      chiral recognition processes primarily capitalizing on strong electrostatic
      intermolecular binding forces. For the investigated compounds, the polar organic
      mode was identified as the most favorable mobile phase scenario, producing the
      highest apparent enantioseparation factors, alpha(app), in combination with the
      lowest degree of non-enantioselective adsorption. It is anticipated that the
      described approach toward the deconvolution of non-enantioselective versus
      enantioselective interactions will also be applicable to other types of brush
      type CSPs. Most important, the quantitative information on the inherent
      thermodynamics of SO-SA interactions emerging from these studies will permit an
      unambiguous interpretation of the changes of the chiral recognition
      characteristics occurring as a consequence of mobile phase modifications. We are
      confident that this knowledge will be helpful in the design and evaluation of new
      non-invasive surface and immobilization chemistries, and will also provide
      valuable guidance for the optimization of operation conditions for large scale
      preparative enantiomer separations. Finally, it should be stressed that the
      advanced strategy for distinguishing enantioselective from non-enantioselective
      contributions has general applicability to all liquid phase-based
      enantioseparation techniques, well beyond the realm of chromatography, such as
      liquid-liquid extraction and batch-binding processes.

PMID- 23127813
TI  - Synthesis and investigation of the anticancer effects of estrone-16-oxime ethers
      in vitro.
AB  - An expanding body of evidence indicates the possible role of estrane derivatives
      as useful anticancer agents. The aim of this study was to describe the cytotoxic
      effects of 63 newly synthetized estrone-16-oxime ethers on human cancer cell
      lines (cervix carcinoma HeLa, breast carcinoma MCF7 and skin epidermoid carcinoma
      A431), studied by means of the MTT assay. Four of the most promising compounds
      were selected for participation in additional experiments in order to
      characterize the mechanism of action, including cell cycle analysis,
      morphological study and the 5-bromo-2'-deoxyuridine incorporation assay. The
      cancer selectivity was tested on a noncancerous fibroblast cell line (MRC-5).
      Since apoptosis and cell cycle disturbance were observed, caspase-3 activities
      were further assayed for the two most effective agents. These estrone-16-oxime
      analogs activated caspase-3 and changed the mRNA level expression of endogenous
      factors regulating the G1-S phase transition (retinoblastoma protein, CDK4 and
      p16). The repression of retinoblastoma protein was reinforced at a protein level
      too. These experimental data lead to the conclusion that estrone-16-oxime ethers
      may be regarded as potential starting structures for the design of novel
      anticancer agents.

PMID- 23127814
TI  - Dynamics of serum testosterone during the menstrual cycle evaluated by daily
      measurements with an ID-LC-MS/MS method and a 2nd generation automated
      immunoassay.
AB  - BACKGROUND: Testosterone concentrations in normally cycling women are assumed to
      be elevated around the time of ovulation. The clinical relevance of changing
      testosterone concentrations during the menstrual cycle, however, is unclear. Poor
      performance of current direct immunoassays for testosterone at low concentrations
      confounds this issue. Therefore, our objective was to assess daily testosterone
      fluctuation during the menstrual cycle by a thoroughly validated isotope dilution
      liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) method and to
      evaluate whether an ARCHITECT(r) 2nd Generation Testosterone fully automated
      immunoassay is equally suited for this purpose. METHODS: Testosterone was
      measured in serum obtained daily during the menstrual cycle of 25 healthy women,
      characterized by biochemical and physical examination. RESULTS: Performance of
      the ID-LC-MS/MS method was concordant with a published reference method (y=1.007x
      0.056 nmol/L; r=0.9998). Comparison of the immunoassay to ID-LC-MS/MS yielded
      y=1.095x+0.104 nmol/L (r=0.9031). Overall, testosterone concentrations were
      higher mid-cycle, but a peak was not discernible in each individual. Apart from a
      persistent positive bias, the immunoassay measured the same testosterone profiles
      as the ID-LC-MS/MS method. The reference interval in women was 0.30-1.69 nmol/L
      (8.7-48.7 ng/dL) for ID-LC-MS/MS and 0.50-2.00 nmol/L (14.4-57.7 ng/dL) for the
      immunoassay. CONCLUSION: The elevation of mid-cycle testosterone concentrations
      is statistically significant, although not clinically relevant since day-to-day
      variation is higher and independent of the menstrual cycle. In this light, a
      single testosterone measurement might not be reflective of the overall
      testosterone status in an individual. Measurements obtained using the 2nd
      generation immunoassay gave comparable results across the menstrual cycle.

PMID- 23127815
TI  - In situ forming microparticle implants for delivery of sex steroids in fish:
      Modulation of the immune response of gilthead seabream by testosterone.
AB  - Current knowledge on the sensitivity of marine fish to androgenic environmental
      chemicals is limited, despite the growing interest in the effects of endocrine
      disrupting chemicals. To study in vivo the effects of testosterone (T) on the
      fish immune response, we used a microencapsulation implant technique, the in situ
      forming microparticle system, containing 1 mg T/kg body weight (T-ISM), in adult
      specimens of gilthead seabream (Sparus aurata L.), a species of great economic
      interest. We demonstrated that implants themselves (without T) have no
      significant effect on most of the parameters measured. In T-ISM implanted fish, T
      serum levels reached supraphysiological concentrations accompanied by a slight
      increase in 11-ketotestosterone and 17beta-estradiol levels 21 days post
      implantation (dpi). Liver and head-kidney samples were processed 7 and 21 dpi to
      assess T-ISM effect on (i) the mRNA expression of genes involved in the
      metabolism of steroid hormones and in the immune response, and (ii) phagocyte
      activities. The expression profile of cytokines, chemokines and immune receptors
      was altered in T-ISM implanted animals that showed an early pro-inflammatory
      tendency, and then, a mixed pro-/anti-inflammatory activation during longer
      exposure. Furthermore, the enhancement of phagocytic activity and the production
      of reactive oxygen species by leukocytes 21 dpi in T-ISM implanted specimens
      suggest fine modulation of the innate immune response by T. Taken together, these
      data demonstrate for the first time the feasibility of using ISM implants in an
      aquatic species, and provide new data on the role played by T on the immune
      response in fish.

PMID- 23127816
TI  - It takes two to tango: dimerisation of glucocorticoid receptor and its anti
      inflammatory functions.
AB  - For a number of years, there has been a widespread view that the adverse side
      effects of prolonged glucocorticoid (GC) treatment are a result of glucocorticoid
      receptor (GR)-mediated gene activation, whilst the beneficial anti-inflammatory
      effects result from GR-mediated 'transrepression'. Since the introduction of the
      dimerisation-deficient GR mutant, GR(dim), was apparently unable to activate gene
      transcription, yet still able to repress pro-inflammatory gene transcription, the
      search for novel GR modulators has centred on the separation of gene activation
      from repression by prevention of GR dimerisation. However, recent work has
      questioned the conclusions drawn from these early GR(dim) studies, with evidence
      that GR(dim) mutants not only activate gene transcription, but that, in direct
      contradiction to the initial GR(dim) work, are also capable of forming dimers.
      This review of the current literature highlights the versatility of the GR in
      forming homodimer interactions, as well as the ability to bind to alternate
      nuclear receptors, and investigates the potential implications such varying GR
      dimer conformations may have for the design of GR ligands with a safer side
      effect profile.

PMID- 23127817
TI  - Synthesis of 6-azaprogesterone and 19-hydroxy-6-azasteroids.
AB  - 19-Hydroxy-6-azapregnanes were obtained from pregnenolone via a 7-azido-5-oxo-6
      nor-5,7-secopregnane intermediate. The 6-azapregnane core was built in good yield
      in a straightforward way from the secosteroid, by means of a Staudinger (aza
      Wittig) reaction. Finally the 19-hydroxy-6-azapregnane was transformed into 19
      hydroxy-6-azaprogesterone (that cyclized spontaneously to the 19->3 hemiketal)
      and 6-azaprogesterone. The 6-azapregnanes lacked agonistic/antagonistic activity
      on the progesterone receptor.

PMID- 23127818
TI  - Synthesis and antitumor activity of N-sulfonyl-3,7-dioxo-5beta-cholan-24-amides,
      ursodeoxycholic acid derivatives.
AB  - A series of N-sulfonyl-3,7-dioxo-5beta-cholan-24-amides, ursodeoxycholic acid
      derivatives, have been designed and synthesized in nine steps starting from
      ursodeoxycholic acid. The in vitro antitumor activity of the target compounds has
      been evaluated against HCT-116, MCF-7, K562, and SGC-7901 cell lines. The
      pharmacological results showed that most of the prepared compounds display
      excellent selective cytotoxicity toward HCT-116, MCF-7, and K562 cell lines.
      Particularly, compounds 10c, 10f and 10g show high inhibitory activity on these
      human cancer cell lines (IC50: 2.39-9.34 MUM). Conversely, all compounds are
      generally inactive against SGC-7901, with only 10b having IC50 below 50 MUM.

PMID- 23127819
TI  - Alternative long-term markers for the detection of methyltestosterone misuse.
AB  - Methyltestosterone (MT) is one of the most frequently detected anabolic
      androgenic steroids in doping control analysis. MT misuse is commonly detected by
      the identification of its two main metabolites excreted as glucuronide
      conjugates, 17alpha-methyl-5alpha-androstan-3alpha,17beta-diol and 17alpha-methyl
      5beta-androstan-3alpha,17beta-diol. The detection of these metabolites is
      normally performed by gas chromatography-mass spectrometry, after previous
      hydrolysis with beta-glucuronidase enzymes, extraction and derivatization steps.
      The aim of the present work was to study the sulphate fraction of MT and to
      evaluate their potential to improve the detection of the misuse of the drug in
      sports. MT was administered to healthy volunteers and urine samples were
      collected up to 30days after administration. After an extraction with ethyl
      acetate, urine extracts were analysed by liquid chromatography tandem mass
      spectrometry using electrospray ionisation in negative mode by monitoring the
      transition m/z 385 to m/z 97. Three diol sulphate metabolites (S1, S2 and S3)
      were detected. Potential structures for these metabolites were proposed after
      solvolysis and mass spectrometric experiments: S1, 17alpha-methyl-5beta-androstan
      3alpha,17beta-diol 3alpha-sulphate; S2, 17beta-methyl-5alpha-androstan
      3alpha,17alpha-diol 3alpha-sulphate; and S3, 17beta-methyl-5beta-androstan
      3alpha,17alpha-diol 3alpha-sulphate. Synthesis of reference compounds will be
      required in order to confirm the structures. The retrospectivity of these
      sulphate metabolites in the detection of MT misuse was compared with the obtained
      with previously described metabolites. Metabolite S2 was detected up to 21days
      after MT administration, improving between 2 and 3 times the retrospectivity of
      the detection compared to the last long-term metabolite of MT previously
      described, 17alpha-hydroxy-17beta-methylandrostan-4,6-dien-3-one.

PMID- 23127820
TI  - Nine new steroidal glycosides from the roots of Cynanchum stauntonii.
AB  - Nine new steroidal glycosides, named as stauntosides C-K (2, 5, 7-10, 13, 14, and
      16), along with seven known compounds (1, 3, 4, 6, 11, 12, and 15) were isolated
      from the 95% ethanol extract of the roots of Cynanchum stauntonii. The structures
      of these new compounds were elucidated on the basis of extensive spectroscopic
      analyses, mainly 1D and 2D NMR, and HRESI-MS, and qualitative chemical methods.
      Their significance in terms of the chemotaxonomy of C. stauntonii is discussed.

PMID- 23127821
TI  - Embryonic stem cells incorporate into newly formed bone and do not form tumors in
      an immunocompetent mouse fracture model.
AB  - Embryonic stem (ES) cells are a uniquely self-renewing, pluripotent population of
      cells that must be differentiated before being useful for cell therapy. Since
      most studies utilize subcutaneous implantation to test the in vivo functionality
      of ES cell-derived cells, the objective of the current study was to develop an
      appropriate and clinically relevant in vivo implantation system in which the
      behavior and tumorigenicity of ES cell-derived cells could be effectively tested
      in a tissue-specific (orthotopic) site. Male ES cells were differentiated either
      into osteoblasts or chondrocytes using protocols that were previously developed
      and published by our laboratory. The differentiated cells were implanted into a
      burr-hole fracture created in the proximal tibiae of immunocompetent female mice,
      strain matched to the ES cell line. The ability of the differentiated ES cell
      derived cells (bearing the Y chromosome) to incorporate into the newly formed
      bone was assessed by micro-computed tomography imaging and histochemistry. ES
      cells differentiated with either osteogenic or chondrogenic medium
      supplementation formed a soft tissue mass that disrupted the normal bone
      architecture by 4 weeks after implantation in some mice. In contrast, mice
      receiving osteoblastic cells that were differentiated in a three-dimensional type
      1 collagen gel showed evidence of new bone formation at the defect site without
      evidence of tumor formation for up to 8 weeks after implantation. In this injury
      model, type 1 collagen is more effective than medium supplementation at driving
      more complete differentiation of ES cells, as evidenced by reducing their
      tumorigenicity. Overall, the current study emphasizes the importance of using an
      appropriate orthotopic implantation system to effectively test the behavior and
      tumorigenicity of the cells in vivo.

PMID- 23127822
TI  - Frequency of periodontal pathogens in equivalent peri-implant and periodontal
      clinical statuses.
AB  - OBJECTIVES: This study tested the hypotheses that there is: (1) higher bacterial
      frequency in peri-implantitis/periodontitis, followed by mucositis/gingivitis and
      peri-implant/periodontal health; (2) similar bacterial frequency between
      comparable peri-implant and periodontal clinical statuses. DESIGN OF STUDY: The
      presence of Porphyromonas gingivalis, Tannerella forsythia, Campylobacter rectus,
      Prevotella intermedia, Treponema denticola and Aggregatibacter
      actinomycetemcomitans was evaluated in peri-implant (n=53) and periodontal (n=53)
      health; mucositis (n=50), gingivitis (n=50), peri-implantitis (n=50) and
      periodontitis (n=50). RESULTS: The pattern of peri-implant bacterial frequency
      was not as expected (peri-implantitis>mucositis>health). Except for P. intermedia
      (p>0.05), bacterial frequency was higher in peri-implantitis than health
      (p<0.05). The frequency of P.gingivalis and red complex species were higher in
      peri-implantitis than mucositis (p<0.05). In periodontal samples, T. forsythia
      and T. denticola showed the expected pattern of frequency
      (periodontitis>gingivitis>health). The frequencies of C. rectus and T. forsythia
      were higher in healthy teeth/gingivitis than healthy implants/mucositis,
      respectively (p<0.05). The frequency of P. gingivalis and A.
      actinomycetemcomitans were similar between periodontitis and peri-implantitis
      (p>0.05) while all other species occurrences were higher in periodontitis than
      peri-implantitis (p<0.05). CONCLUSIONS: Bacterial frequency increased from peri
      implant/periodontal health to peri-implantitis/periodontitis but not from
      mucositis/gingivitis to peri-implantitis/periodontitis. There was a trend towards
      higher bacterial frequency in teeth than implants.

PMID- 23127823
TI  - Increased expression of CD4+IL-17+ cells in the lung tissue of patients with
      stable chronic obstructive pulmonary disease (COPD) and smokers.
AB  - CD4(+)IL-17(+) cells have an important role in controlling immune and
      inflammatory reactions. The authors of the present study hypothesize that these
      cells may be involved in the pathogenesis of chronic obstructive pulmonary
      disease (COPD). To characterize the frequency of CD4(+)IL-17(+) cells in the lung
      alveolar walls, small airways and muscular pulmonary arteries of nonsmokers,
      smokers with normal lung function and COPD patients, CD4(+)IL-17(+) cell number
      was assessed using double immunofluorescence staining, and IL-17 and IL-21
      expression were measured using real-time quantitative PCR in the peripheral lung
      tissues of 10 nonsmokers, 10 smokers with normal lung function and 10 smokers
      with stable COPD. In the lung alveolar walls, the number of CD4(+)IL-17(+) cells
      was increased in COPD patients compared with nonsmokers and in normal smokers
      compared with nonsmokers. In the small airways, the CD4(+)IL-17(+) cell numbers
      were higher in COPD patients than in normal smokers and nonsmokers. A positive
      correlation was observed between CD4(+)IL-17(+) cell expression and pathological
      changes in the lung tissue. In the small airways, the number of CD4(+)IL-17(+)
      cells was positively correlated with airflow limitations. The IL-17 mRNA levels
      in lung tissues were increased in COPD patients and normal smokers compared with
      nonsmokers. Increased CD4(+)IL-17(+) cell number in lung tissue is involved in
      chronic inflammation of the lungs and parallels lung injury aggravation in COPD
      patients and in smokers without airway limitations. These findings contribute to
      a better understanding of CD4(+) cell-related pathogenesis in COPD.

PMID- 23127824
TI  - Cells and materials for liver tissue engineering.
AB  - Liver transplantation is currently the most efficacious treatment for end-stage
      liver diseases. However, one main problem with liver transplantation is the
      limited number of donor organs that are available. Therefore, liver tissue
      engineering based on cell transplantation that combines materials to mimic the
      liver is under investigation with the goal of restoring normal liver functions.
      Tissue engineering aims to mimic the interactions among cells with a scaffold.
      Particular materials or a matrix serve as a scaffold and provide a three
      dimensional environment for cell proliferation and interaction. Moreover, the
      scaffold plays a role in regulating cell maturation and function via these
      interactions. In cultures of hepatic lineage cells, regulation of cell
      proliferation and specific function using biocompatible synthetic, biodegradable
      bioderived matrices, protein-coated materials, surface-modified nanofibers, and
      decellularized biomatrix has been demonstrated. Furthermore, beneficial effects
      of addition of growth factor cocktails to a flow bioreactor or coculture system
      on cell viability and function have been observed. In addition, a system for
      growing stem cells, liver progenitor cells, and primary hepatocytes for
      transplantation into animal models was developed, which produces hepatic lineage
      cells that are functional and that show long-term proliferation following
      transplantation. The major limitation of cells proliferated with matrix-based
      transplantation systems is the high initial cell loss and dysfunction, which may
      be due to the absence of blood flow and the changes in nutrients. Thus, the
      development of vascular-like scaffold structures, the formation of functional
      bile ducts, and the maintenance of complex metabolic functions remain as major
      problems in hepatic tissue engineering and will need to be addressed to enable
      further advances toward clinical applications. 

PMID- 23127825
TI  - Precipitation of Ibuprofen Sodium using compressed carbon dioxide as antisolvent.
AB  - Precipitation with compressed antisolvent (PCA) process was used to produce fine
      particles of Ibuprofen Sodium with the ultimate goal of obtaining controlled
      particle size and size distribution of this non-steroidal anti-inflammatory drug.
      This systematic investigation shows that particle size and size distribution of
      the final product can be controlled reproducibly by varying a number operating
      parameters such as antisolvent addition rate, temperature, concentration, and
      solution addition rate. The mechanisms that control particle size and particle
      size distribution were explained by invoking the differences in the relative
      weight of primary, secondary nucleation and growth kinetic phenomena. A number of
      techniques were used for the characterization of the generated particles. In
      addition to scanning electron microscope (SEM), dynamic light scattering
      measurements were conducted to determine the size of the particles in terms of
      number-weighted size distribution. The influence of process parameters on the
      Ibuprofen Sodium crystallinity was investigated using X-ray diffraction (XRD).
      Moreover, the ''in vitro'' drug performance was tested. The results showed an
      improvement of the PCA processed Ibuprofen Sodium ''in vitro'' drug activity. In
      addition, dissolution investigations demonstrated that the flow rate, in
      combination with the particle size distribution, substantially influence the drug
      "in vitro" dissolution.

PMID- 23127826
TI  - Structure-based design of flavone derivatives as c-myc oncogene down-regulators.
AB  - Based on molecular docking analysis of complexes between flavone and the c-myc G
      quadruplex, we designed and screened 30 flavone derivatives containing various
      side chains that could potentially form interactions with the G-quadruplex
      grooves. As a proof-of-concept, the highest-scoring flavone derivatives
      containing cationic pyridinium side chains were synthesized and their
      interactions with the c-myc G-quadruplex were examined using a PCR-stop assay.
      The stabilizing effects of the flavone derivatives were found to be selective
      towards the c-myc G-quadruplex over other biologically relevant G-quadruplex
      structures, such as the human telomeric sequence (HTS). The interaction between
      the most potent compound of the series and the c-myc G-quadruplex was examined in
      depth using UV-Vis titration, molecular modeling and CD spectroscopy. Our results
      suggest that in addition to stabilizing the c-myc G-quadruplex, the flavone
      derivatives were capable of inducing the formation of the G-quadruplex structure
      even in the absence of monovalent cations. The flavone derivatives were found to
      be potent inhibitors of c-myc promoters within the cellular environment and
      displayed promising cytotoxic behavior against human cancer cell lines.

PMID- 23127827
TI  - Parachutes for diabetes: bariatric surgery beyond evidence?

PMID- 23127828
TI  - Reply: To PMID 22541246.

PMID- 23127829
TI  - A role for food allergy testing in eosinophilic esophagitis.

PMID- 23127830
TI  - Chemical, structural and combustion characteristics of carbonaceous products
      obtained by hydrothermal carbonization of palm empty fruit bunches.
AB  - A carbon-rich solid product, denoted as hydrochar, was synthesized by
      hydrothermal carbonization (HTC) of palm oil empty fruit bunch (EFB), at
      different pre-treatment temperatures of 150, 250 and 350  degrees C. The
      conversion of the raw biomass to its hydrochar occurred via dehydration and
      decarboxylation processes. The hydrochar produced at 350  degrees C had the
      maximum energy-density (>27 MJ kg(-1)) with 68.52% of raw EFB energy retained in
      the char. To gain a detailed insight into the chemical and structural properties,
      carbonaceous hydrochar materials were characterized by FE-SEM, FT-IR, XRD and
      Brunauer-Emmett-Teller (BET) analyses. This work also investigated the influence
      of hydrothermally treated hydrochars on the co-combustion characteristics of low
      rank Indonesian coal. Conventional thermal gravimetric analysis (TGA) parameters,
      kinetics and activation energy of different hydrochar and coal blends were
      estimated. Our results show that solid hydrochars improve the combustion of low
      rank coals for energy generation.

PMID- 23127831
TI  - Hydrothermal treatment and enzymatic hydrolysis of Tamarix ramosissima:
      evaluation of the process as a conversion method in a biorefinery concept.
AB  - The present work investigated the effects of hydrothermal treatment (HTT) of
      Tamarix ramosissima by determination of sugar and inhibitor formation in the
      liquid fraction, and chemical and morphological changes of the pretreated solid
      material coupled with an evaluation of enzymatic hydrolysis. HTT was carried out
      in a batch reactor system at a maximal temperature (TMAX 180-240  degrees C) and
      evaluated for severities logRo ranging from 2.40 to 4.17. The liquid fractions
      were analyzed by HPLC, GPC, and GC-MS. The morphology and composition of the
      solid residues were characterized using an array of techniques, such as SEM, XRD,
      BET surface area, and CP/MAS (13)C NMR. Using a variety of tools, we have
      developed a better understanding of how HTT process affects biomass structure and
      cellulose properties that impact on its digestibility. These results provided new
      insights into the factors limiting enzymatic digestibility and mechanism of
      biomass deconstruction during hydrothermal process.

PMID- 23127832
TI  - Refactoring redox cofactor regeneration for high-yield biocatalysis of glucose to
      butyric acid in Escherichia coli.
AB  - In this study, the native redox cofactor regeneration system in Escherichia coli
      was engineered for the production of butyric acid. The synthetic butyrate
      pathway, which regenerates NAD(+) from NADH using butyrate as the only final
      electron acceptor, enabled high-yield production of butyric acid from glucose
      (83.4% of the molar theoretical yield). The high selectivity for butyrate, with a
      butyrate/acetate ratio of 41, suggests dramatically improved industrial potential
      for the production of butyric acid from nonnative hosts compared to the native
      producers (Clostridium species). Furthermore, this strategy could be broadly
      utilized for the production of various other useful chemicals in the fields of
      metabolic engineering and synthetic biology.

PMID- 23127833
TI  - Zygomycetes-based biorefinery: present status and future prospects.
AB  - Fungi of the phylum Zygomycetes fulfil all requirements for being utilized as
      core catalysts in biorefineries, and would be useful in creating new sustainable
      products. Apart from the extended use of Zygomycetes in preparing fermented
      foods, industrial metabolites such as lactic acid, fumaric acid, and ethanol are
      produced from a vast array of feedstocks with the aid of Zygomycetes. These fungi
      produce enzymes that facilitate their assimilation of various complex substrates,
      e.g., starch, cellulose, phytic acid, and proteins, which is relevant from an
      industrial point of view. The enzymes produced are capable of catalyzing various
      reactions involved in biodiesel production, preparation of corticosteroid drugs,
      etc. Biomass produced with the aid of Zygomycetes consists of proteins with
      superior amino acid composition, but also lipids and chitosan. The biomass is
      presently being tested for animal feed purposes, such as fish feed, as well as
      for lipid extraction and chitosan production. Complete or partial employment of
      Zygomycetes in biorefining procedures is consequently attractive, and is expected
      to be implemented within a near future.

PMID- 23127834
TI  - Ferric iron enhances electricity generation by Shewanella oneidensis MR-1 in
      MFCs.
AB  - Fe(III) supplemented into microbial fuel cells (MFC) at initial start-up
      increased electricity generation by Shewanella oneidensis MR-1. The maximum power
      density reached 158.1 mW/m(2) with 6 mM Fe(III), compared with 73.9 mW/m(2)
      without Fe(III). A significant increase in power output was observed when MFC
      with established biofilm in the absence of Fe(III) was supplemented with Fe(III)
      afterward. The cell biomass of the anode biofilm of MFCs operated in the presence
      of Fe(III) was higher than that obtained without Fe(III). An optimum
      concentration of Fe(III) obviously improved electrochemical activity and the
      flavins secretion of strain MR-1. The results demonstrated that Fe(III) addition
      can enhance power generation by strain MR-1 due to the increase of cell biomass
      and flavins secretion.

PMID- 23127835
TI  - Enhancing butanol production with Clostridium pasteurianum CH4 using sequential
      glucose-glycerol addition and simultaneous dual-substrate cultivation strategies.
AB  - Adding butyrate significantly enhanced butanol production from glycerol with
      Clostridium pasteurianum CH4, which predominantly produces butyrate (instead of
      butanol) when grown on glucose. Hence, the butyrate produced from assimilating
      glucose can be used to stimulate butanol production from glycerol under dual
      substrate cultivation with glucose and glycerol. This proposed butanol production
      process was conducted by employing sequential or simultaneous addition of the two
      substrates. The latter approach exhibited better carbon source utilization and
      butanol production efficiencies. Under the optimal glucose to glycerol ratio (20
      g L(-1) to 60 g L(-1)), the simultaneous dual-substrate strategy obtained maximum
      butanol titer, productivity and yield of 13.3 g L(-1), 0.28 g L(-1) h(-1), and
      0.38 mol butanol/mol glycerol, respectively. Moreover, bagasse and crude glycerol
      as dual-substrates were also converted into butanol efficiently with a maximum
      butanol concentration, productivity and yield of 11.8 g L(-1), 0.14 g L(-1) h(
      1), and 0.33 mol butanol/mol glycerol, respectively.

PMID- 23127836
TI  - Simultaneous saccharification and high titer lactic acid fermentation of corn
      stover using a newly isolated lactic acid bacterium Pediococcus acidilactici DQ2.
AB  - A lactic acid bacterium with high tolerance of temperature and lignocellulose
      derived inhibitor was isolated and characterized as Pediococcus acidilactici DQ2.
      The strain used in the simultaneous saccharification and fermentation (SSF) for
      high titer lactic acid production at the high solids loading of corn stover. Corn
      stover was pretreated using the dry sulphuric acid pretreatment, followed by a
      biological detoxification to remove the inhibitors produced in the pretreatment.
      The bioreactor with a novel helical impeller was used to the SSF operation of the
      pretreated and biodetoxified corn stover. The results show that a typical SSF
      operation at 48  degrees C, pH 5.5, and near 30% (w/w) solids loading in both 5
      and 50 L bioreactors was demonstrated. The lactic acid titer, yield, and
      productivity reached 101.9 g/L, 77.2%, and 1.06 g/L/h, respectively. The result
      provided a practical process option for cellulosic lactic acid production using
      virgin agriculture lignocellulose residues.

PMID- 23127837
TI  - High glucose selectivity in pressurized water hydrolysis of cellulose using ultra
      fast reactors.
AB  - A new reactor was developed for the selective hydrolysis of cellulose. In this
      study, the glucose selectivity obtained from cellulose was improved by using
      ultra-fast reactions in which a selective medium was combined with an effective
      residence time control. A selective production of glucose, fructose and
      cellobiose (50%) or total mono-oligo saccharides (>96%) was obtained from the
      cellulose in a reaction time of 0.03 s. Total cellulose conversion was achieved
      with a 5-hydroxymethylfural concentration lower than 5 ppm in a novel micro
      reactor. Reducing the residence time from minutes to milliseconds opens the
      possibility of moving from the conventional m(3) to cm(3) reactor volumes.

PMID- 23127838
TI  - Biotransformation of p-coumaric acid and 2,4-dichlorophenoxy acetic acid by
      Azotobacter sp. strain SSB81.
AB  - A comprehensive study was made on biotransformation of p-coumaric acid and 2,4
      dichlorophenoxyacetic acid by an Azotobacter sp. strain SSB81. The strain was
      able to tolerate a high amount of both the phenolic acids and p-coumaric acid
      degraded maximum (50%) than 2,4-D (29%) after five days of incubation. The
      intermediate products during transformation have been identified and quantified
      using UV-Vis and LC-MS/MS analysis. Para-coumaric acid was degraded via p
      hydroxybenzoic acid and protocatechuic acid, a non-oxidative pathway whereas 2,4
      D via 4-chlorophenoxyacetic acid, 4-chlorophenol and 4-chlorocatechol, an
      oxidative pathway. The results suggest that SSB81 developed both the oxidative
      and non-oxidative pathway to degrade the soil accumulated phenolic acids. Thus,
      Azotobacter provides an advantage to reduce the toxic level of soil accumulated
      phenolic acids in addition to increase the soil fertility.

PMID- 23127839
TI  - Bioconversion characteristics of Rhodopseudomonas palustris CQK 01 entrapped in a
      photobioreactor for hydrogen production.
AB  - The performance of the entrapped-cell photobioreactor during H2 production was
      assessed by using glucose as substrate in a continuous operation mode. The
      maximal hydrogen production rate and light conversion efficiency, 2.61 mmol/L/h
      and 82.3%, were obtained at a HRT of 11.4 h, an substrate loading rate of 4.2
      mmol/h and an illumination of 590 nm and 6000 lux, the corresponding hydrogen
      yield and total energy efficiency were 0.62 mmol H2/(mmol glucose) and 4.8%,
      respectively. The results indicate the H2 production system illuminated at 590 nm
      wavelength engaged in energy storage for H2 production due to more ATP
      synthesized in primary reaction center, and was of higher energy recovery
      capacity. Furthermore, the total energy efficiency was far lower than the
      corresponding light conversion efficiency due to intermediates production.

PMID- 23127840
TI  - Batch and multi-step fed-batch enzymatic saccharification of Formiline-pretreated
      sugarcane bagasse at high solid loadings for high sugar and ethanol titers.
AB  - Formiline pretreatment pertains to a biomass fractionation process. In the
      present work, Formiline-pretreated sugarcane bagasse was hydrolyzed with
      cellulases by batch and multi-step fed-batch processes at 20% solid loading. For
      wet pulp, after 144 h incubation with cellulase loading of 10 FPU/g dry solid,
      fed-batch process obtained ~150 g/L glucose and ~80% glucan conversion, while
      batch process obtained ~130 g/L glucose with corresponding ~70% glucan
      conversion. Solid loading could be further increased to 30% for the acetone-dried
      pulp. By fed-batch hydrolysis of the dried pulp in pH 4.8 buffer solution,
      glucose concentration could be 247.3+/-1.6 g/L with corresponding 86.1+/-0.6%
      glucan conversion. The enzymatic hydrolyzates could be well converted to ethanol
      by a subsequent fermentation using Saccharomices cerevisiae with ethanol titer of
      60-70 g/L. Batch and fed-batch SSF indicated that Formiline-pretreated substrate
      showed excellent fermentability. The final ethanol concentration was 80 g/L with
      corresponding 82.7% of theoretical yield.

PMID- 23127841
TI  - Qualitative analysis of the stability of a continuous vermicomposting system.
AB  - A mathematical model was established to describe ecological relationships in a
      continuous vermicomposting system. The distributions of organic matter, microbes
      and earthworms on non-dimensional specific growth rates were simulated. The range
      of specific growth rates were visualized utilizing three-dimensional
      reconstruction technology. The stability of a vermicomposting system was not
      influenced by the initial concentrations of microbes and earthworms, only their
      species. The coordinates of the stable point depended on the dilution rate and
      initial amount of organic matter. The method described could be help for
      establishing a stable continuous vermicomposting system.

PMID- 23127842
TI  - Preparation and characteristics of bioflocculants from excess biological sludge.
AB  - In this study the feasibility of preparing bioflocculant from excess biological
      sludge was investigated. Hydrochloric acid was used to disintegrate sludge to
      prepare bioflocculant. The effects of acid dosage and flocculating conditions
      were studied. The optimized disintegration conditions was that acid dosage was 10
      mL for 50 mL sludge suspension. Factors such as bioflocculant dosage, pH and
      temperature of the flocculant system were also tested. The optimal conditions
      were flocculant concentration 3.0% (v/v) and pH10.5 of flocculating suspension.
      Under these conditions, 99.5% of flocculating rate for 4 g/L kaolin clay was
      achieved. Ethanol and sodium hydroxide were applied to purify the crude sludge
      bioflocculant together or separately. Results showed that sodium hydroxide could
      separate the bioflocculant from aqueous solution more effectively than ethanol.
      Analysis of the purified bioflocculant by Fourier-transform infrared
      spectrophotometer (FT-IR) and chemical methods indicated that the main component
      was polysaccharide. Performance test showed that the sludge bioflocculant had
      moderate thermostability.

PMID- 23127843
TI  - Open fermentative production of L-lactic acid by Bacillus sp. strain NL01 using
      lignocellulosic hydrolyzates as low-cost raw material.
AB  - Highly efficient L-lactate production by a thermophilic strain Bacillus sp. NL01
      was demonstrated in this study. Lignocellulosic hydrolyzates containing a high
      content of glucose, which was prepared from corn stover, was used as substrate
      for L-lactic acid production. The fermentation was carried out under open
      condition without sterilization and used NaOH as alkaline neutralizing reagent.
      In batch fermentation, 56.37 g l(-1) L-lactic acid was obtained from
      lignocellulosic hydrolyzates which contained the solid residues produced in
      enzymatic saccharification. In fed-batch fermentation, 75.03 g l(-1) L-lactic
      acid was obtained from lignocellulosic hydrolyzates supernatant. The yield was
      74.5% and the average productivity was 1.04 g l(-1) h(-1).

PMID- 23127844
TI  - Sodium sulfite-formaldehyde pretreatment of mixed hardwoods and its effect on
      enzymatic hydrolysis.
AB  - In this work, mixed hardwoods were pretreated by sodium sulfite-formaldehyde
      (SF). The effects of SF pretreatment on the chemical compositions and enzymatic
      hydrolysis of mixed hardwoods were investigated. SF pretreatment temperature had
      a significant effect on pulp yield and delignification, resulting in an increased
      efficiency of enzymatic hydrolysis. After 96 h of enzymatic hydrolysis at the
      cellulase loading of 40 FPU/g substrate, the yields of glucan and xylan on the
      basis of original wood were 37% and 11% for the pulp produced with 12% sulfite
      charge at 170  degrees C for 2 h. The total sugar recovery based on the sugar in
      original wood was 74%. These results indicate that sulfite-formaldehyde cooking
      is of great potential to be a pretreatment method for a greenfield mill to
      produce fuel ethanol from hardwood.

PMID- 23127845
TI  - Butanol production in a first-generation Brazilian sugarcane biorefinery:
      technical aspects and economics of greenfield projects.
AB  - The techno-economics of greenfield projects of a first-generation sugarcane
      biorefinery aimed to produce ethanol, sugar, power, and n-butanol was conducted
      taking into account different butanol fermentation technologies (regular
      microorganism and mutant strain with improved butanol yield) and market scenarios
      (chemicals and automotive fuel). The complete sugarcane biorefinery with the
      batch acetone-butanol-ethanol (ABE) fermentation process was simulated using
      Aspen Plus(r). The biorefinery was designed to process 2 million tonne sugarcane
      per year and utilize 25%, 50%, and 25% of the available sugarcane juice to
      produce sugar, ethanol, and butanol, respectively. The investment on a
      biorefinery with butanol production showed to be more attractive [14.8% IRR,
      P(IRR>12%)=0.99] than the conventional 50:50 (ethanol:sugar) annexed plant [13.3%
      IRR, P(IRR>12%)=0.80] only in the case butanol is produced by an improved
      microorganism and traded as a chemical.

PMID- 23127846
TI  - Protective effect of edaravone against Alzheimer's disease-relevant insults in
      neuroblastoma N2a cells.
AB  - Oxidative stress has been demonstrated to be involved in the pathogenesis of
      Alzheimer's disease (AD). Thus, antioxidant therapy may represent a promising
      avenue for the treatment of AD. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one)
      is a potent free radical scavenger and has been shown to provide neuroprotection
      in both animal models of cerebral ischemia and stroke patients. In the present
      study, we investigated the protective effect of edaravone against AD-relevant
      insults in neuroblastoma N2a cells and explored the potential mechanisms
      involved. N2a/Swe.Delta9 cells were used as the AD model cells, which exhibited
      reduced cell viability, increased apoptosis and oxidative stress as well as
      decreased mitochondrial membrane potential compared with N2a/Wt cells. All of
      these phenotypes were significantly reversed by edaravone treatment. Edaravone
      treatment significantly elevated cell viability, reduced apoptotic rate,
      attenuated oxidative stress and improved mitochondrial membrane potential in
      N2a/Swe.Delta9 cells. Furthermore, edaravone treatment inhibited mitochondria
      dependent apoptosis pathways in N2a/Swe.Delta9 cells through decreasing the
      Bax/Bcl-2 ratio, attenuating cytochrome c release and suppressing the activation
      of caspase-3. These results demonstrate that edaravone provides neuroprotection
      in an AD-related in vitro model and therefore, may be a potential complement for
      AD therapy.

PMID- 23127847
TI  - CNS penetration of the opioid glycopeptide MMP-2200: a microdialysis study.
AB  - Endogenous opioid peptides enkephalin and dynorphin are major co-transmitters of
      striatofugal pathways of the basal ganglia. They are involved in the genesis of
      levodopa-induced dyskinesia and in the modulation of direct and indirect striatal
      output pathways that are disrupted in Parkinson's disease. One pharmacologic
      approach is to develop synthetic glycopeptides closely resembling endogenous
      peptides to restore their normal functions. Glycosylation promotes penetration of
      the blood-brain barrier. We investigated CNS penetration of the opioid
      glycopeptide MMP-2200, a mixed delta/MU-agonist based on leu-enkephalin, as
      measured by in vivo microdialysis and subsequent mass spectrometric analysis in
      awake, freely moving rats. The glycopeptide (10 mg/kg) reaches the dorsolateral
      striatum (DLS) rapidly after systemic (i.p.) administration and is stably
      detectable for the duration of the experiment (80 min). The detected level at the
      end of the experiment (around 250 pM) is about 10-fold higher than the level of
      the endogenous leu-enkephalin, measured simultaneously. This is one of the first
      studies to directly prove that glycosylation of an endogenous opioid peptide
      leads to excellent blood-brain barrier penetration after systemic injection, and
      explains robust behavioral effects seen in previous studies by measuring how much
      glycopeptide reaches the target structure, in this case the DLS.

PMID- 23127848
TI  - Chronic dopamine depletion augments the functional expression of K-ATP channels
      in the rat subthalamic nucleus.
AB  - Symptoms of Parkinson's disease caused by dopamine depletion are associated with
      burst firing in the subthalamic nucleus (STN). Moreover, regularization or
      suppression of STN neuronal activity is thought to improve symptoms of
      Parkinson's disease. We reported recently that N-methyl-D-aspartate (NMDA)
      receptor stimulation of rat STN neurons evokes ATP-sensitive K(+) (K-ATP) current
      via a Ca(2+)- and nitric oxide-dependent mechanism. The present studies were done
      to determine whether or not K-ATP channel function in STN neurons is altered in a
      model of chronic dopamine depletion. Brain slices were prepared from rats with
      unilateral dopamine depletion caused by intracerebral 6-hydroxydopamine (6-OHDA)
      injections. Whole-cell patch-clamp recordings showed that NMDA evoked more
      outward current at -70 mV and greater positive slope conductance in STN neurons
      located ipsilateral to 6-OHDA treatment compared to neurons located
      contralateral. Moreover, extracellular, loose-patch recordings showed that NMDA
      increased spontaneous firing rate in STN neurons in slices from normal rats,
      whereas NMDA produced a tolbutamide-sensitive inhibition of firing rate in STN
      neurons located ipsilateral to 6-OHDA treatment. These results show that K-ATP
      channel function in STN neurons is up-regulated by chronic dopamine deficiency.
      We suggest that K-ATP channel activation in the STN might benefit symptoms of
      Parkinson's disease.

PMID- 23127849
TI  - Characterization of embryonic cortical neuron death in prolonged cell suspension.
AB  - Cell transplantation may be an effective therapeutic strategy for many
      neurodegenerative diseases. However, difficulty in obtaining a sufficient amount
      of donor cells and low graft survival are two major limiting factors.
      Dissociation of cells from tissues or culture is an inevitable step for cell
      transplantation, and cell viability in suspension may influence the outcome of
      the cell therapy. To this end, we asked whether the suspension time of freshly
      dissociated neurons in vitro affects their viability. Following 4-24h cell
      suspension, primary cortical neurons underwent cell death. Interestingly, the
      neurons exhibited only marginal caspase-3 immunoreactivity with very few sub-G1
      apoptotic cell proportions in flow cytometry. In addition, the suppression of
      caspase-3 or Bax action failed to prevent cell death of primary cortical neurons,
      indicating minimal apoptotic cell death. On the other hand, there was a marked
      increase in the TdT-mediated dUTP nick end labeling-positive and propidium iodide
      labeled necrotic cells (~50%) with enhanced poly [ADP-ribose] polymerase-1
      activity. Therefore, prevention against necrosis rather than apoptosis may be
      required for optimal benefits in cell transplantation.

PMID- 23127850
TI  - Forskolin induced increase in spontaneous activity of auditory brainstem neurons
      is comparable to acoustic stimulus evoked responses.
AB  - Contemporary proposals for the pathophysiology of tinnitus due to cochlear damage
      underscore increased spontaneous activity of auditory brainstem neurons. One of
      the several consequences of the cochlear injury is the activation of the ERK
      pathway, suppression of phosphodiestase E activity, and putatively setting a long
      term increase in intracellular levels of cyclic AMP at central auditory neurons.
      Local application of forskolin also increases intracellular cyclic AMP and
      spontaneous neural activity. We measured the effects of locally applied forskolin
      on spontaneous firing rate of isolated neurons in the peri-olivary region of the
      superior olive complex in anesthetized adult Long Evan rats. Forskolin induced
      increase in spontaneous neural activity was comparable to supra-threshold tone
      evoke neural responses. These results are viewed in context of hyperexcitability
      as a correlate of tinnitus.

PMID- 23127851
TI  - Anxiolytic and hypnotic effects in mice of roasted coffee bean volatile
      compounds.
AB  - To clarify the relationship between the volatile compounds present in roasted
      coffee beans and psychological stress, we investigated the stress-reducing
      potential of coffee volatiles in mice using a variety of behavioral pharmacology
      methods. In the elevated plus-maze test, exposure to coffee volatiles increased
      the time spent in and the number of entries into the open arms without increasing
      spontaneous locomotor activity. Pentobarbital-induced sleep time was prolonged by
      volatile exposure. No significant effects were detected in the open-field or
      forced-swim tests. These results suggest that coffee volatiles lower the arousal
      level and exert anti-anxiety-like, stress-reducing effects in mice.

PMID- 23127852
TI  - Atorvastatin stimulates neuroblastoma cells to induce neurite outgrowth by
      increasing cellular prion protein expression.
AB  - Recently, 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors
      were reported to induce neurite outgrowth in vitro. However, the mechanism
      underlying this effect remains unclear. Cellular prion protein (PrP(C)) is a
      ubiquitous glycoprotein present on the surfaces of various cells, including
      neurons, and is suggested to be involved in neurite outgrowth. Therefore, the
      present study aimed to determine whether PrP(C) mediates neurite outgrowth
      induced by HMG-CoA reductase inhibitors. Atorvastatin, a strong HMG-CoA reductase
      inhibitor, induced neurite outgrowth and increased PrP(C) levels in Neuro2a cells
      in a time- and dose-dependent manner. PrP(C) mRNA expression was also increased
      by atorvastatin. Farnesol, a non-sterol mevalonate derivative, attenuated the
      atorvastatin-induced neurite outgrowth and increase in PrP(C). Neuro2a cells
      overexpressing PrP(C) showed a remarkable enhancement of atorvastatin-induced
      neurite outgrowth compared with mock cells transfected with empty pCI-neo vector.
      These findings suggest that PrP(C) contributes, at least in part, to atorvastatin
      induced neurite outgrowth. This phenomenon may be included among the mechanisms
      underlying decreased risk of Alzheimer's disease in patients treated with HMG-CoA
      reductase inhibitors.

PMID- 23127853
TI  - The size of motoneurons of the gastrocnemius muscle in rats with diabetes.
AB  - Alterations in the number and size of motoneurons were studied in the medial
      gastrocnemius (MG) motor nucleus of diabetic rats (12 or 22 weeks after injection
      of storeptozotocin) and age-matched controls. Each group contained 6 animals. MG
      motoneurons were retrogradely labeled by dextran-fluorescein and the number and
      size of cell bodies were examined. Significantly fewer labeled MG motoneurons
      were found in the 22-week diabetic rats as compared with age-matched control
      animals. The mean soma diameter of MG motoneurons was significantly smaller in
      the 12- and 22-week diabetic animals. Furthermore the soma size for 22-week
      diabetic animals was smaller than for 12-week diabetic animals. The distribution
      of average soma diameters in the MG nucleus of control animals was bimodal; cells
      with larger average diameter were presumed to be alpha-motoneurons and those with
      smaller diameters were presumed to be gamma. Compared to control animals, the
      number of smaller MG motoneurons was reduced in 12 week diabetic animals. By 22
      weeks, diabetic animals had no small MG motoneurons and the size distribution
      became unimodal. We conclude that there is a significant decrease in the absolute
      number and size of MG motoneurons in diabetic rats, with the possibility that the
      decrease occurred predominantly among the smaller gamma-motoneurons.

PMID- 23127855
TI  - BACE1 levels are elevated in congestive heart failure.
AB  - Cardiovascular (CV) diseases are known to have a negative impact on the brain and
      neurocognition, and contribute to the development of vascular dementia and
      neurodegenerative diseases such as Alzheimer's disease (AD). Among CV diseases,
      congestive heart failure (CHF) after myocardial infarction (MI) is a condition
      where the ability of the left ventricle to eject blood to the circulation is
      impaired. As a consequence, CHF triggers inflammation and results in reduced
      cerebral blood flow which are considered among the risk factors for development
      of AD. However, biochemical alterations in the brain following MI and CHF remain
      unknown. To address this issue, we investigated microglia activation; levels of
      BACE1, the key rate-limiting enzyme involved in the pathogenesis of AD; and VEGF
      levels in the hippocampus and cortex following MI. We created MI by the ligation
      of the left anterior descending coronary artery in Sprague-Dawley male rats and
      collected brains either 3 days after MI (AMI) or 21 days after MI (CHF). We
      investigated microglia activation in AMI and CHF brains by immunohistochemistry
      and immunoblotting using macrophage/microglia marker Ionized calcium binding
      adaptor molecule 1 (Iba-1), and observed activated morphology of microglia in the
      cortex of rats in both AMI and CHF. We also showed the levels of BACE1 were
      increased in the cortex and hippocampus of CHF rats. To determine whether hypoxia
      occurs in the CHF brain, we assessed levels of VEGF in the hippocampus and
      cortex. Western blotting analysis showed up-regulation of VEGF in the hippocampus
      of CHF brains. These results suggest that neuroinflammation takes place secondary
      to myocardial infarction. In addition, CHF-induced hypoxia might play a role in
      the elevation of BACE1 and VEGF levels.

PMID- 23127856
TI  - Mesenspheres of neural crest-derived cells enriched from bone marrow stromal cell
      subpopulation.
AB  - Neural crest-derived cells (NCCs) can be used for cell replacement therapy of
      neurodegenerative diseases and nerve injury, and it is of significance to open
      readily accessible tissue sources for NCCs due to their insufficient supply. In
      this study, we aimed to examine the possibility of enriching NCCs from bone
      marrow stromal cell (BMSC) subpopulation. The epidermal growth factor/fibroblast
      growth factor-2 (EGF/FGF2)-responsive BMSC subpopulation (BMSC-C2) was isolated
      from rat bone marrow by repetitive two-step condition culture. The BMSC-C2
      subpopulation showed a long-term proliferative capacity and high cell growth
      rate, and possessed a significant sphere-forming ability. The mesenspheres
      derived from BMSC-C2 subpopulation were self-renewable and could express NCC
      markers, such as CD29, CD44, nestin, CD133 and p75(NTR). In particular, the
      mesenspheres could be induced to differentiate into neuron- and glia-like cells
      in vitro. Collectively, our results might provide a basis for in-depth studies of
      recruiting postmigratory NCCs from bone marrow and various neural crest-derived
      tissues.

PMID- 23127854
TI  - Okadaic acid induces Akt hyperphosphorylation and an oxidative stress-mediated
      cell death in serum starved SK-N-SH human neuroblastoma cells that are augmented
      by rapamycin.
AB  - Using a neuronal model of serum starved SK-N-SH neuroblastoma cells, we showed
      previously that the phosphorylation of Akt and the mTOR substrates S6K and S6
      through the vascular endothelial growth factor receptor VEGFR2 was enhanced by
      treatments with the phosphatase PP2A inhibitor okadaic acid (OA). These findings
      suggested that PP2A inhibition uncouples the regulation of Akt signaling by mTOR
      and affects cell survival. We therefore examined the effects of mTOR inhibition
      on Akt phosphorylation at sites threonine 308 (T308) and serine 473 (S473) and
      survival in OA treated cells. OA induced a loss in cell viability, the
      accumulation of hyperactivated Akt as monomeric and ubiquitinated forms and an
      increase in the total levels of ubiquitinated proteins. These events were
      exacerbated by treatments with an allosteric (rapamycin) but not an active-site
      inhibitor (PP242) of mTOR. Notably, rapamycin augmented the OA-induced
      hyperphosphorylation of Akt by suppressing a negative feedback loop of Akt
      activation through VEGFR2 and its downstream target phosphatidylinositol 3-kinase
      (PI3K). Treatments with the antioxidant N-acetlycysteine but not the pan caspase
      inhibitor Z-VAD-FMK promoted survival. Unlike reports that rapamycin promotes
      survival through increased Akt activation, these findings show that rapamycin
      induced hyperphosphorylation of Akt fails to rescue our neuronal model from an
      oxidative stress-induced and caspase-independent cell death mediated by PP2A
      inhibition. Moreover, the exacerbation of OA-induced events by rapamycin suggests
      that mTOR and PP2A work in concert to regulate cell survival, activated Akt and
      the levels of ubiquitinated proteins.

PMID- 23127857
TI  - One's own name distorts visual space.
AB  - Here, we demonstrated that one's own name attracts the subjective location of a
      visual target. We simultaneously presented observers their own name and others'
      name in the left and right visual fields. A target circle was presented for 53 ms
      around the center of the display 200 ms after the names disappeared. Ten
      observers were required to manually reproduce the target location by pointing
      with the mouse. The results indicated that the observers significantly
      mislocalized the target 1.61' on average toward the location of their own name.
      These observations indicated that the visual space is distorted by one's own
      name, which biases the spatial distribution of visual attention.

PMID- 23127858
TI  - Big pharma screening collections: more of the same or unique libraries? The
      AstraZeneca-Bayer Pharma AG case.
AB  - In this study, the screening collections of two major pharmaceutical companies
      (AstraZeneca and Bayer Pharma AG) have been compared using a 2D molecular
      fingerprint by a nearest neighborhood approach. Results revealed a low overlap
      between both collections in terms of compound identity and similarity. This
      emphasizes the value of screening multiple compound collections to expand the
      chemical space that can be accessed by high-throughput screening (HTS). 

PMID- 23127859
TI  - Reverse engineering the antigenic architecture of the haemagglutinin from
      influenza H5N1 clade 1 and 2.2 viruses with fine epitope mapping using monoclonal
      antibodies.
AB  - The induction of neutralising antibodies to the viral surface glycoprotein,
      haemagglutinin (HA) is considered the cornerstone of current seasonal and
      pandemic influenza vaccines. Mapping of neutralising epitopes using monoclonal
      antibodies (mAbs) helps define mechanisms of antigenic drift, neutralising escape
      and facilitates pre-pandemic vaccine design. In the present study we reverse
      engineered the antigenic structure of the HAs of two highly pathogenic H5N1
      vaccine strains representative of currently circulating clade 1 and 2.2 H5N1
      viruses. The HA sequence of the A/Vietnam/1194/04 clade 1 virus was progressively
      mutated into the HA sequence of the clade 2.2 virus, A/Bar-headed
      Goose/Qinghai/1A/05. Fine mapping of clade-specific neutralising epitopes was
      performed by examining the cross-reactivity of mAbs raised against the native HA
      of each parent virus. The reactivity across all clade specific mAbs centred
      around a constellation of mutations at positions 140, 145, 171 and 172, all of
      which are proximal to the receptor binding site on the membrane distal globular
      head of the HA. Overlapping cross-reactivity of these antigenic sites suggests
      that these amino acid positions relate to the antigenic evolution of the H5 clade
      1 and 2.2 viruses. This finding may prove useful for the design of vaccines with
      broader neutralising cross-reactivity against the different H5 HA sublineages
      currently in circulation. These findings provide important information about the
      amino acid changes involved in the cross-clade evolution of H5N1 viruses and
      their potential for human to human transmission; and facilitates a greater
      understanding of the pandemic potential of H5N1 isolates.

PMID- 23127860
TI  - The anti-oxidative, anti-inflammatory, and protective effect of S100A8 in
      endotoxemic mice.
AB  - Polymorphonuclear neutrophils (PMNs) produce and release copious amounts of
      reactive oxygen species (ROS) which target potential bacterial invaders but also
      contribute to the inflammation-associated organ injuries seen in sepsis.
      Calprotectin is an immune regulatory protein complex made of S100A8 and S100A9
      that inhibits the oxidative metabolism of PMNs in vitro, an effect that can be
      potentiated by the controlled activation of the protease activated receptor-2
      (PAR2). The aim of this study was to test the use of a dual strategy of
      calprotectin and PAR2 administration to mitigate the deleterious inflammation
      seen in sepsis. We hypothesized that exogenous calprotectin would protect against
      the injuries produced by lipopolysaccharides (LPS)-induced endotoxemia and that
      the controlled activation of PAR2 would potentiate this beneficial effect.
      Exogenous S100A8 and/or a PAR2 activating peptide (PAR2 AP) were administered in
      a mouse model of LPS induced endotoxemia. The survival rates as well as markers
      of inflammation and oxidative damage were measured in the lungs, kidneys, and
      livers of endotoxemic mice. Mice treated with S100A8 following LPS had less PMN
      infiltration and less severe histological changes in their lungs, kidneys, and
      livers. A significantly lower score of oxidative damage in the livers and lungs
      of S100A8/LPS treated mice was also noted when compared to mice treated with LPS
      alone. This protective and anti-inflammatory effect of S100A8 was potentiated by
      the controlled activation of PAR2. Finally, in further support to our hypothesis,
      the survival rate was almost doubled from 33% to 65% and 63% in mice treated by,
      respectively, S100A8 and PAR2 AP, whereas 85% of the mice treated with both PAR2
      AP and S100A8 survived, a statistically significant higher rate. These results
      support an anti-inflammatory, anti-oxidative, and protective effect of S100A8 in
      sepsis, and warrant further studies on the role of PAR2.

PMID- 23127861
TI  - Formic acid poisoning in a tertiary care center in South India: A 2-year
      retrospective analysis of clinical profile and predictors of mortality.
AB  - BACKGROUND: Formic acid (FA), a common industrial compound, is used in the
      coagulation of rubber latex in Kerala, a state in southwestern India. Easy
      accessibility to FA in this region makes it available to be used for deliberate
      self-harm. However, the literature on intentional poisoning with FA is limited.
      STUDY OBJECTIVES: To determine the patterns of presentation of patients with
      intentional ingestion of FA and to find the predictors of mortality. A secondary
      objective was to find the prevalence and predictors of long-term sequelae related
      to the event. METHODS: We performed a 2-year chart review of patients with acute
      intentional ingestion of FA. Symptoms, signs, outcomes and complications were
      recorded, and patients who survived the attempt were followed-up by telephone or
      personal interview to identify any complications after their discharge from the
      hospital. RESULTS: A total of 302 patients with acute formic acid ingestion were
      identified during the study period. The mortality rate was 35.4% (n = 107). Bowel
      perforation (n = 39), shock (n = 73), and tracheoesophageal fistula (n = 4) were
      associated with 100% mortality. Quantity of FA consumed (p < 0.001), consuming
      undiluted FA (p < 0.001), presenting symptoms of hypotension (p < 0.001),
      respiratory distress (p < 0.001), severe degree of burns (p = 0.020), hematemesis
      (p = 0.024), complications like metabolic acidosis (p < 0.001) and acute
      respiratory distress syndrome (p < 0.001) were found to have significant
      association with mortality. The prevalence of esophageal stricture (n = 98) was
      50.2% among survivors and was the most common long-term sequela among the
      survivors. Stricture was significantly associated with hematemesis (p < 0.001)
      and melena (p < 0.001). CONCLUSION: This study highlights the magnitude and ill
      effects of self-harm caused by a strong corrosive, readily available due to very
      few restrictions in its distribution. Easy availability of FA needs to be
      curtailed by enforcing statutory limitations in this part of the world. Patients
      with hematemesis or melena after FA ingestion may be referred for early
      dilatation therapy in a setting where emergency endoscopic evaluation of all
      injured patients is not practical.

PMID- 23127862
TI  - The Food and Drug Administration is nearing the end of its debate on the life
      threatening use of cornstarch powder on medical gloves.

PMID- 23127863
TI  - Patterns of measles transmission among airplane travelers.
AB  - With advanced air handling systems on modern aircraft and the high level of
      measles immunity in many countries, measles infection in air travelers may be
      considered a low-risk event. However, introduction of measles into countries
      where transmission has been controlled or eliminated can have substantial
      consequences both for the use of public health resources and for those still
      susceptible. In an effort to balance the relatively low likelihood of disease
      transmission among largely immune travelers and the risk to the public health of
      the occurrence of secondary cases resulting from importations, criteria in the
      United States for contact investigations for measles exposures consider contacts
      to be those passengers who are seated within 2 rows of the index case. However,
      recent work has shown that cabin air flow may not be as reliable a barrier to the
      spread of measles virus as previously believed. Along with these new studies,
      several reports have described measles developing after travel in passengers
      seated some distance from the index case. To understand better the potential for
      measles virus to spread on an airplane, reports of apparent secondary cases
      occurring in co-travelers of passengers with infectious cases of measles were
      reviewed. MedlineTM was searched for articles in all languages from 1946 to week
      1 of March 2012, using the search terms "measles [human] or rubeola" and
      ("aircraft" or "airplane" or "aeroplane" or "aviation" or "travel" or "traveler"
      or "traveller"); 45 citations were returned. EmbaseTM was searched from 1988 to
      week 11 2012, using the same search strategy; 95 citations were returned. Papers
      were included in this review if they reported secondary cases of measles
      occurring in persons traveling on an airplane on which a person or persons with
      measles also flew, and which included the seating location of both the index
      case(s) and the secondary case(s) on the plane. Nine reports, including 13 index
      cases and 23 apparent secondary cases on 10 flights, were identified in which
      transmission on board the aircraft appeared likely and which included seating
      information for both the index (primary) and secondary cases. Separation between
      index and secondary cases ranged from adjacent seats to 17 rows, with a median of
      6 rows. Three flights had more than one index case aboard. Based on previously
      published data, it is not possible to say how unusual cases of measles
      transmission among air travelers beyond the usual zone of contact investigation
      (the row the index case sat in and 2 rows ahead of or behind that row) may be.
      The fact that several flights had more than one infectious case aboard and that
      all but two index cases were in the prodromal phase may be of importance in
      understanding the wider spread described in several of the reviewed reports.
      Although the pattern of cabin air flow typical of modern commercial aircraft has
      been considered highly effective in limiting the airborne spread of
      microorganisms, concerns have been raised about relying on the operation of these
      systems to determine exposure risk, as turbulence in the cabin air stream is
      generated when passengers and crew are aboard, allowing the transmission of
      infectious agents over many rows. Additionally, the characteristics of some index
      cases may reflect a greater likelihood of disease transmission. Investigators
      should continue to examine carefully both aircraft and index-case factors that
      may influence disease transmission and could serve as indicators on a case-by
      case basis to include a broader group of travelers in a contact investigation.

PMID- 23127864
TI  - Aorto-enteric fistula development secondary to mycotic abdominal aortic aneurysm
      following intravesical bacillus Calmette-Guerin (BCG) treatment for transitional
      cell carcinoma of the bladder.
AB  - INTRODUCTION: Intravesical BCG-instillation for bladder cancer is considered safe
      but is not without risk. While most side-effects are localised and self-limiting,
      the development of secondary vascular pathology is a rare but significant
      complication. PRESENTATION OF CASE: A 77-year-old male presented with a mycotic
      abdominal aortic aneurysm and associated aorto-enteric fistula 18 months after
      receiving intravesical BCG-instillations for early stage transitional cell
      carcinoma. DISCUSSION: Response rates to intravesical BCG for early stage
      transitional cell carcinoma are high. The procedure produces a localised
      inflammatory response in the bladder but the exact mechanism of action is
      unclear. The treatment is generally well tolerated but BCG-sepsis and secondary
      vascular complications have been documented. Mycotic abdominal aortic aneurysm
      with associated aorto-enteric fistula secondary to BCG is very rare. Few examples
      have been documented internationally and the extent of corresponding research and
      associated management proposals is limited. Surgical options include in situ
      repair with prosthetic graft, debridement with extra-anatomical bypass and,
      occasionally, endovascular stent grafting. Recommended medical therapy for
      systemic BCG infection is Isoniazid, Rifampicin and Ethambutol. CONCLUSION:
      Current screening methods must be updated with clarification regarding duration
      of anti-tuberculous therapy and impact of concomitant anti-tuberculous medication
      on the therapeutic action of intravesical BCG. Long-term outcomes for patients
      post graft repair for mycotic aneurysm are unknown and more research is required
      regarding the susceptibility of vascular grafts to mycobacterial infection.
      Recognition of the risks associated with BCG-instillations, even in
      immunocompetent subjects, is paramount and must be considered even several months
      or years after receiving the therapy.

PMID- 23127865
TI  - Primary pulmonary carcinoid tumor with metastasis to endometrial polyp.
AB  - INTRODUCTION: A carcinoid tumor occurring in the endometrium has been documented
      in the literature, but there is no report in regard to carcinoid tumor metastasis
      to endometrium. PRESENTATION OF CASE: We report a case of a malignant carcinoid
      metastasis to an endometrial polyp. Patient underwent hysteroscopy, and
      polypectomy. The pathology demonstrated an endometrial polyp containing a 4 mm x
      5 mm nodule of metastatic carcinoid tumor, consistent with metastasis from
      patient's known pulmonary carcinoid. The tumor was morphologically similar to the
      tumors of the right lung, with similar immune-profile. DISCUSSION: This patient
      presented with a suspicious pelvic ultrasound. Due to her age, the first priority
      was to exclude uterine cancer. The endometrial polyp, which was found, had a
      small focus of metastatic carcinoid tumor. To the best of our knowledge, this
      finding has not been previously recorded in the literature. Our patient also had
      a history of metastatic carcinoid tumor to breast. This finding is also very
      uncommon. CONCLUSION: This is the first case in the literature described a
      malignant carcinoid metastasis to an endometrial polyp.

PMID- 23127866
TI  - An explicit transition density expansion for a multi-allelic Wright-Fisher
      diffusion with general diploid selection.
AB  - Characterizing time-evolution of allele frequencies in a population is a
      fundamental problem in population genetics. In the Wright-Fisher diffusion, such
      dynamics is captured by the transition density function, which satisfies well
      known partial differential equations. For a multi-allelic model with general
      diploid selection, various theoretical results exist on representations of the
      transition density, but finding an explicit formula has remained a difficult
      problem. In this paper, a technique recently developed for a diallelic model is
      extended to find an explicit transition density for an arbitrary number of
      alleles, under a general diploid selection model with recurrent parent
      independent mutation. Specifically, the method finds the eigenvalues and
      eigenfunctions of the generator associated with the multi-allelic diffusion, thus
      yielding an accurate spectral representation of the transition density.
      Furthermore, this approach allows for efficient, accurate computation of various
      other quantities of interest, including the normalizing constant of the
      stationary distribution and the rate of convergence to this distribution.

PMID- 23127867
TI  - Cross-linked gold nanoparticles on polyethylene: resistive responses to tensile
      strain and vapors.
AB  - In this study, coatings of cross-linked gold nanoparticles (AuNPs) on flexible
      polyethylene (PE) substrates were prepared via layer-by-layer deposition and
      their application as strain gauges and chemiresistors was investigated. Special
      emphasis was placed on characterizing the influence of strain on the
      chemiresistive responses. The coatings were deposited using amine stabilized
      AuNPs (4 and 9 nm diameter) and 1,9-nonanedithiol (NDT) or pentaerythritol
      tetrakis(3-mercaptopropionate) (PTM) as cross-linkers. To prepare films with
      homogeneous optical appearance, it was necessary to treat the substrates with
      oxygen plasma directly before film assembly. SEM images revealed film thicknesses
      between ~60 and ~90 nm and a porous nanoscale morphology. All films showed ohmic
      I-V characteristics with conductivities ranging from 1 * 10-4 to 1 * 10-2 Omega-1
      cm-1, depending on the structure of the linker and the nanoparticle size. When up
      to 3% strain was induced their resistance increased linearly and reversibly
      (gauge factors: ~20). A comparative SEM investigation indicated that the stress
      induced formation and extension of nanocracks are important components of the
      signal transduction mechanism. Further, all films responded with a reversible
      increase in resistance when dosed with toluene, 4-methyl-2-pentanone, 1-propanol
      or water vapor (concentrations: 50-10 000 ppm). Films deposited onto high density
      PE substrates showed much faster response-recovery dynamics than films deposited
      onto low density PE. The chemical selectivity of the coatings was controlled by
      the chemical nature of the cross-linkers, with the highest sensitivities (~1 * 10
      5 ppm-1) measured with analytes of matching solubility. The response isotherms of
      all film/vapor pairs could be fitted using a Langmuir-Henry model suggesting
      selective and bulk sorption. Under tensile stress (1% strain) all chemiresistors
      showed a reversible increase in their response amplitudes (~30%), regardless of
      the analytes' permittivity. Taking into consideration the thermally activated
      tunneling model for charge transport, this behavior was assigned to stress
      induced formation of nanocracks, which enhance the films' ability to swell in
      lateral direction during analyte sorption.

PMID- 23127868
TI  - How to improve housing conditions of laboratory animals: the possibilities of
      environmental refinement.
AB  - Housing systems for captive animals have often been designed on the basis of
      economic and ergonomic considerations, such as equipment, costs, space, workload,
      ability to observe the animals and to maintain a certain degree of hygiene, with
      little or no consideration for animal welfare. Environmental refinement can be
      defined as any modification in the environment of captive animals that seeks to
      enhance the physical and psychological well-being of the animals by providing
      stimuli which meet the animals' species-specific needs. This article provides an
      overview of environmental factors that influence the well-being of captive
      animals with specific reference to the needs of the most common laboratory
      species. It is important to evaluate environmental refinement in terms of the
      benefit to the animal, by assessing the use of and preference for certain
      enrichment, the effect on behaviour, and the performance of species-typical
      behaviour on physiological parameters. It is also necessary to evaluate the
      impact of refinement on scientific outcome, including whether and how statistical
      power is affected. Communication and team work between animal welfare scientists,
      animal research scientists, institutional animal welfare officers, veterinarians
      and animal ethics committees, animal facility management and personnel, are
      essential for success.

PMID- 23127869
TI  - Back in the driver's seat and the need for an objective evaluation of saddle fit.

PMID- 23127870
TI  - Personalized medicine in veterinary oncology: minimal residual disease and
      circulating tumour cells in dogs.

PMID- 23127871
TI  - Cadmium sulphide quantum dots sensitized hierarchical bismuth oxybromide
      microsphere with highly efficient photocatalytic activity.
AB  - Cadmium sulphide (CdS) quantum dots (QDs) sensitized that hierarchical bismuth
      oxybromide (BiOBr) photocatalysts were synthesized via a facile solvothermal
      approach for the first time, which were characterized by XRD, XPS, SEM, TEM, PL,
      and UV-vis DRS spectra. The photocatalytic activities were evaluated by the
      decomposition of methyl orange (MO) under visible light irradiation with
      commercial TiO(2) Degussa P25 as reference. The results revealed that CdS-BiOBr
      photocatalysts had strong light absorption in the visible light region compared
      with pure BiOBr. All CdS-BiOBr photocatalysts possessed higher photocatalytic
      activity than pure BiOBr and Degussa P25 under the visible light irradiation. The
      highest activity was obtained by 2%CdS-BiOBr. The enhanced photocatalytic
      performances were attributed to the matched band potentials of CdS QDs and BiOBr,
      which resulted in the efficient separation of photogenerated electron-hole pairs.
      Based on the experimental results, a reasonable photocatalytic mechanism over CdS
      BiOBr photocatalysts was proposed. And the photodegradation of MO are associated
      with ()O(2)(-) radicals and the photogenerated holes on the valance bands of CdS
      QDs and BiOBr.

PMID- 23127872
TI  - Synthesis, self-assembly, and pH-responsive behavior of (photo-crosslinked) star
      amphiphilic triblock copolymer.
AB  - Conventional polymeric micelles employed as drug carriers suffer from the
      drawback of disaggregation when diluted into body fluids, giving rise to
      premature release of drugs. In this work, cinnamate was chosen as a crosslinker
      to overcome this issue and regulate pH response. A series of photo-crosslinkable
      star amphiphilic triblock copolymers, star poly(epsilon-caprolactone)-b-poly(2
      cinnamoyloxyethyl methacrylate)-b-poly(2-(dimethylamino)ethyl methacrylate) (SPCL
      b-PCEMA-b-PDMAEMA), were prepared by combination of stepwise reversible addition
      fragment chain transfer (RAFT) polymerization and carbodiimide-mediated coupling
      reaction. These star amphiphilic copolymers could self-assemble into core-shell
      corona micelles. Facile photo crosslinking of the micelles was carried out via UV
      irradiation. The crosslinked micelles showed an improved stability determined by
      critical micelle concentration (CMC). The degree of photo crosslinking was easily
      regulated by tuning UV irradiation time, and the hydrodynamic diameters (D(h))
      decreased with increasing degree of photo crosslinking. The pH responses of
      micelles were investigated by dynamic light scattering (DLS), indicating pH
      induced swelling-shrinking behavior. For photo-crosslinked micelle, its
      capability of swelling-shrinking weakened with increasing crosslinking degree,
      suggesting that pH response was controlled by crosslinking density. This novel
      photo-crosslinked micelle system with adjustable pH response was expected to have
      potential as drug carriers for controlled release.

PMID- 23127873
TI  - 23Na and 35/37Cl as NMR probes of growth and shape of sodium taurodeoxycholate
      micellar aggregates in the presence of NaCl.
AB  - The growth of the aggregates of the dihydroxylated bile salt sodium
      taurodeoxycholate (NaTDC) upon NaCl addition and the involvement of the
      counterion were investigated by NMR spectroscopy of monoatomic ionic species.
      (23)Na T(1) values from 0.015, 0.100, and 0.200 mol kg(-1) NaTDC solutions in
      D(2)O, at variable NaCl content, proved to be sensitive to the transition from
      primary to secondary aggregates, which occurs in the former sample, and to
      intermicellar interaction. Some (79)Br NMR measurements were performed on a 0.100
      mol kg(-1) NaTDC sample added by NaBr in place of NaCl for comparison purposes.
      The (23)Na, (35)Cl, and (37)Cl double quantum filtered (DQF) patterns, from the
      0.100 mol kg(-1) NaTDC sample, and (23)Na ones also from the 0.200 mol kg(-1)
      NaTDC one, in the presence of 0.750 mol kg(-1) NaCl, are a clear manifestation of
      motional anisotropy. Moreover, the DQF spectra of (23)Na and (37)Cl, which
      possess close quadrupole moments, display a striking similarity. The DQF
      lineshapes were simulated exploiting the Scilab environment to obtain an estimate
      of the residual quadrupole splitting magnitude. These results support the
      description of NaTDC micelles as cylindrical aggregates, strongly interacting at
      high ionic strengths, and capable of association with added electrolytes.

PMID- 23127874
TI  - Controllable synthesis of Cu2O petalody octahedral microcrystals and multi
      patterned evolution.
AB  - The fabrication of cuprous oxide (Cu(2)O) with various morphologies has attracted
      extensive interest due to its applications in solar energy conversion, electrode
      materials, sensors, and catalysts. Herein, we report a facile controllable route
      for Cu(2)O microcrystals with various architectures via a hydrothermal method
      without using templates or surfactants. Six types of Cu(2)O microcrystals
      including petalody octahedral, concave truncated octahedron, truncated
      octahedron, octahedron, sphere-like, and sphere are obtained accompanying with Cu
      precipitation or urchin-like CuO particles due to the modifying of pH values. The
      petalody octahedral pattern of Cu(2)O is for the first time found here under the
      condition of pH 7-8. Additionally, possible growth mechanism for multi-patterned
      Cu(2)O and compositional evolution is discussed via preferential growths induced
      by selective absorption of acrylic acid and decomposition of lactic acid in the
      present reaction system. These experimental results prove a versatile and facile
      strategy for Cu(2)O microcrystals with special and complex architectures, which
      may highlights their potential applications due to the improved surface activity,
      catalytic, or photoelectric performance.

PMID- 23127875
TI  - Core-shell gold/silver nanoparticles: synthesis and optical properties.
AB  - Highly dispersed gold-silver core-shell nanoparticles were synthesized in a two
      step process. The stabilizer-free gold core particles with an average diameter of
      ~30 nm were first precipitated by rapid reduction of HAuCl(4) with l-ascorbic
      acid. Thin continuous silver shells of variable thickness were subsequently
      obtained by reducing controlled amounts of silver nitrate added in the gold sol.
      The plasmon band of gold gradually blue-shifted and a peak characteristic for
      silver eventually emerged as the amount of deposited silver increased. A strong
      and well-defined silver absorption band was recorded when the Ag content exceeded
      60 wt.%. It is shown that the concentration of Cl(-) ions in the gold precursor
      solution plays a critical role in the stability of the bi-metallic sol and the
      structure of the deposited silver shell.

PMID- 23127876
TI  - Temperature-dependent phosphorus precipitation and chromium removal from struvite
      saturated solutions.
AB  - The effect of temperature from 25 to 300 degrees C on the precipitation of
      phosphorus (P) from struvite-saturated (MgNH(4)PO(4).6H(2)O) solutions was
      explored. Scanning electron microscopy (SEM) revealed reduced particle size and a
      change in morphology from elongated to rhombohedral crystals with temperature. X
      ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR)
      indicated that at 25 degrees C, the precipitate was struvite, while newberyite
      (MgHPO(4).3H(2)O) formed at 100 degrees C, and magnesium pyrophosphate
      (Mg(2)P(2)O(7)) at 300 degrees C. Increased temperature reduced the association
      of ammonium and water of crystallization with the solid and increased P
      polymerization. The behavior of dissolved chromium (Cr) under these conditions
      was also assessed. Removal of Cr with the solid phase from Cr(III) solutions was
      observed at all temperatures, whereas removal from Cr(VI) solutions was
      significant only at 300 degrees C. X-ray absorption fine structure spectroscopy
      (XAFS) revealed that regardless of initial oxidation state in solution, Cr(III)
      was associated with the solid, interacting by the adsorption of short-range Cr
      polymers. Therefore, for struvite-saturated solutions, increasing the temperature
      changed both the mineralogy of the P phase recovered and enhanced the interaction
      of otherwise unreactive Cr(VI) with the substrate. These results have
      implications for the temperature-enhanced recovery of P from wastewater.

PMID- 23127877
TI  - Covalent molecular assembly: construction of ultrathin multilayer films by a two
      dimensional fabrication method.
AB  - A two-dimensional fabrication method was employed to assemble ultrathin
      multilayer films with specific three-dimensional structures by making use of
      interlayer and intralayer covalent bonding. The films were assembled in a layer
      wise fashion on a silicon surface using bi- and multi-functional molecules as
      building blocks and strengthened by lateral cross-linking. The fabrication
      process could be controlled at the sub-nano-scale with the roughness of the
      surface after deposition of each layer within 0.2 nm. The film showed better
      resistance to harsh environments than randomly cross-linked or linearly linked
      films of comparable thickness. The combination of covalent LbL assembly and
      lateral cross-linking has significant potential as a method of fabrication for
      assembling nano-structures for a variety of applications.

PMID- 23127878
TI  - Thermodynamics of hydrophobic interaction between silica surfaces coated with
      octadecyltrichlorosilane.
AB  - Surface force measurements conducted with thiolated gold surfaces showed
      previously that hydrophobic interaction entails a decrease in excess film
      entropy, suggesting that hydrophobic force originates from changes in the
      structure of the medium (water) confined between hydrophobic surfaces. As a
      follow-up work, surface force measurements have been conducted in the present
      work using an atomic force microscope (AFM) with silica surfaces coated with
      octadecyltrichlorosilane (OTS) at temperatures in the range of 10-40 degrees C. A
      thermodynamic analysis of the results show that both the excess film entropy
      (DeltaS(f)) and excess film enthalpy (DeltaH(f)) decrease with decreasing
      thickness of the water films between the hydrophobic surfaces. It has been found
      also that |DeltaH(f)|>|TDeltaS(f)|, which represents a necessary condition for
      the excess free energy change (DeltaG(f)) to be negative and hence the
      hydrophobic interaction be attractive. Thus, the results obtained with both the
      thiolated and silylated surfaces show that hydrophobic forces originate from the
      structural changes in the medium. It is believed that the water molecules in the
      thin liquid films (TLFs) of water form clusters as a means to reduce the free
      energy when they cannot form H-bonds to neighboring hydrophobic surfaces.

PMID- 23127879
TI  - Maximizing usability of evidence in rehabilitation practice: tips for
      researchers.
AB  - The ultimate goal of rehabilitation research is to improve the lives of people
      with disabilities; yet, little research is implemented into clinical practice.
      The objectives of the current article are to serve as a guide for rehabilitation
      researchers regarding factors that contribute to translation of the evidence base
      in clinical practice, to highlight some common problems encountered by clinicians
      when trying to implement evidence-based treatments, and to provide tips that
      researchers can use to enhance the likelihood of their research products being
      used in clinical practice. The impact of clinician and environmental factors on
      use of evidence-based medicine are reviewed. Practical issues encountered by
      clinicians when attempting to translate evidence-based findings into practice are
      highlighted by discussing 2 areas of research: compensatory strategies for memory
      impairment after brain injury and use of electrical stimulation for weakness and
      paralysis in persons with spinal cord injury. The article closes with a series of
      tips to assist researchers in translating findings to clinicians.

PMID- 23127880
TI  - Introduction to special issue on the neurobiology of depression.

PMID- 23127881
TI  - Enhanced NMDA receptor tyrosine phosphorylation and increased brain injury
      following neonatal hypoxia-ischemia in mice with neuronal Fyn overexpression.
AB  - The Src family kinases (SFKs) Src and Fyn are implicated in hypoxic-ischemic (HI)
      injury in the developing brain. However, it is unclear how these particular SFKs
      contribute to brain injury. Using neuron-specific Fyn overexpressing (OE) mice,
      we investigated the role of neuronal Fyn in neonatal brain HI. Wild type (WT) and
      Fyn OE mice were subjected to HI using the Vannucci model at postnatal day 7.
      Brains were scored five days later for evaluation of damage using cresyl violet
      and iron staining. Western blotting with postsynaptic density (PSD)-associated
      synaptic membrane proteins and co-immunoprecipitation with cortical lysates were
      performed at various time points after HI to determine NMDA receptor tyrosine
      phosphorylation and Fyn kinase activity. Fyn OE mice had significantly higher
      mortality and brain injury compared to their WT littermates. Neuronal Fyn
      overexpression led to sustained NR2A and NR2B tyrosine phosphorylation and
      enhanced NR2B phosphorylation at tyrosine (Y) 1472 and Y1252 in synaptic
      membranes. These early changes correlated with higher calpain activity 24h after
      HI in Fyn OE mice relative to WT animals. Our findings suggest a role for Fyn
      kinase in neuronal death after neonatal HI, possibly via up-regulation of NMDA
      receptor tyrosine phosphorylation.

PMID- 23127882
TI  - Executive dysfunction is the primary cognitive impairment in progressive
      supranuclear palsy.
AB  - Cognitive difficulties appear to be a more prevalent clinical feature in
      progressive supranuclear palsy (PSP) than previously thought, and significant
      cognitive impairment is prevalent in a majority of patients PSP patients not
      considered clinically demented. The neurocognitive performance of 200 patients
      with PSP across multiple sites was examined with a variety of commonly used
      neuropsychological tests. Results indicate primary executive dysfunction (e.g.,
      74% impaired on the Frontal Assessment Battery, 55% impaired on
      Initiation/Perseveration subscale of the Dementia Rating Scale), with milder
      difficulties in memory, construction, and naming. These results have important
      clinical implications for providers following patients with PSP.

PMID- 23127883
TI  - Facial affect recognition in CADASIL patients.
AB  - We explored the capacity of Cerebral Autosomal-Dominant Arteriopathy with
      Subcortical Infarcts and Leukoencephalopathy (CADASIL) patients to recognize
      facial expressions. Twenty-three consecutive CADASIL patients and 23 age-matched,
      gender-matched, and education-matched controls were assessed with a semi
      structured psychiatric interview, cognitive tests, and the Ekman and Friesen
      test. Cases and controls (5 males, 18 females) had a mean age (+SD) of 52.4 +
      15.7 and 54.0 + 15.3 years, respectively, and a Mini-Mental State Examination
      (MMSE) mean score of 27.8 + 2.2 and 28.9 + 1.3 (p < .05). Eighteen out of the 23
      (78.3%) CADASIL patients and 10 (43.5%) controls were diagnosed as affected by
      major depression according to DSM-IV criteria (p < .05). The CADASIL patients had
      an impaired ability of emotion recognition in comparison with controls,
      particularly for fear expression. This effect was not mediated by depression,
      cognitive impairment, and MMSE score. Facial affect recognition is reduced in the
      CADASIL patients and this impairment might represent an early manifestation of
      the disease.

PMID- 23127884
TI  - Synaptic plasticity, but not hippocampal neurogenesis, mediated the counteractive
      effect of wolfberry on depression in rats(1).
AB  - Depression is a life-threatening psychiatric disorder characterized with a long
      term hypercortisolemia in depressed patients. Based on this clinical feature,
      hypercortisolemia was mimicked in experimental animals to understand the
      neuropathogy of depression and to explore new therapeutic  strategies. Wolfberry,
      also known as Lycium barbarum, is a type of common fruit produced in mainland
      China. Accumulated evidence has shown that the extracts from Lycium barbarum
      (LBP) had a wide range of neuroprotective effects in various neurogenerative
      models. However, the  antidepressant effect of LBP on depression and its
      mechanism has not yet been explored. In the present study, we investigated the
      effects of LBP on counteracting depression using an animal model injected with
      moderate dose (40 mg/kg) or severe dose (50 mg/kg) of corticosterone (CORT)
      treatments  for 14 days. The results showed that CORT significantly increased
      immobility time and decreased hippocampal cell proliferation. LBP treatment
      significantly decreased the immobility time in forced swimming test, a test for
      the intensity of depressive behaviors, both in 40 and 50 mg/kg CORT  stressed
      rats. Moreover, LBP treatment restored the reduced proliferation of
      neuroprogentior cells in the hippocampus in 40 mg/kg CORT stressed rats and the
      neuronal differentiation but not the proliferation in 50 mg/kg CORT stressed
      rats. After ablation of adult neurogenesis with Ara-c infusion,  the beneficial
      effect of LBP treatment in reducing immobility time was not affected in 40 and 50
      mg/kg CORT stressed rats. Golgi staining and Western blotting detection showed
      that LBP treatment restored the reduced spine density and the decreased level of
      PSD-95 in the hippocampus caused  by 40 and 50 mg/kg CORT, respectively,
      indicating enhanced synaptic plasticity in the hippocampus. The data showed a
      novel effect of LBP on reducing depression-like behavior and its antidepressant
      effect may be mediated by enhanced synaptic plasticity, but not hippocampal
      neurogenesis.

PMID- 23127885
TI  - Structure-related cytotoxic activity of derivatives from kulokekahilide-2, a
      cyclodepsipeptide in Hawaiian marine mollusk.
AB  - Kulokekahilide-2, a 26-membered cyclodepsipeptide, was isolated from Hawaiian
      marine mollusk and possessed potent cytotoxicity in mammalian tumor cells. In the
      present study, we synthesized kulokekahilide-2 and its derivatives and examined
      the structure-activity relationships of these peptides in human cancer cells
      (A549, K562, and MCF7 cells). This study demonstrated that the cyclization of
      depsipeptide and the chirality of the 21 position in Ala in kulokekahilide-2 were
      important for its cytotoxic property and that addition of halogen at the para
      position of phenyl group in the 24-D-MePhe in kulokekahilide-2 as well as some
      derivatives remarkably increased their cytotoxicity in human cancer cells. These
      results suggest that the modifications of 24-D-MePhe in kulokekahilide-2,
      preserving its cyclization and the chirality at the 21-position, are promising
      strategy for exploring new derivative of kulokekahilide-2 as anti-tumor drug.

PMID- 23127886
TI  - Compounds from the heartwood of Caesalpinia sappan and their anti-inflammatory
      activity.
AB  - Two new phenolics, (3S,4R)-3,7,2',3'-tetrahydroxy-3,4-dihydro-9H-indeno[6,5
      c]chromene (caesalpiniaphenol E, 1), and (3R,4S)-3,7-dihydroxy-3-(3'-methoxy-4'
      hydroxyphenyl)-4-methoxychroman (caesalpiniaphenol F, 2), together with eleven
      known compounds (3-13), were isolated from the heartwood of Caesalpinia sappan.
      Their chemical structures were established mainly by 1D and 2D NMR techniques and
      mass spectrometry. Their anti-inflammatory activity was evaluated against LPS
      induced NO production in macrophage RAW264.7 cells. Among them, compounds 10 and
      13 showed strong inhibitory activities toward the LPS-induced NO production in
      macrophage RAW264.7 cells, with IC(50) values of 12.5 and 8.1 MUm, respectively.
      In addition, compounds 10 and 13 inhibited the inductions of iNOS mRNA in dose
      dependent manners, indicating that these compounds attenuated the synthesis of
      these transcripts at the transcriptional level.

PMID- 23127887
TI  - Heterologously expressed beta-hydroxyl fatty acids from a metagenomic library of
      a marine sponge.
AB  - Functional screening based on the antibacterial activity of a metagenomic library
      of the Japanese marine sponge, Discodermia calyx, afforded three beta-hydroxyl
      fatty acids: 3-hydroxypalmitic acid, 3-hydroxylauric acid and 3-hydroxymyristic
      acid, heterologously expressed in an antibacterial clone, pDC113. 3
      Hydroxypalmitic acid showed moderate antibacterial activity against Bacillus
      cereus and Candida albicans. A sequence analysis of the insert DNA revealed 23
      putative ORFs, with most sharing homology to bacterial fatty acid synthase II and
      lipid A biosynthesis enzymes. The other ORFs were probably transmembrane proteins
      involved in lipid A biosynthesis. Although lipid A was not detected under our
      experimental conditions, the production of beta-hydroxyl fatty acids as
      components of lipid A were enhanced in pDC113.

PMID- 23127889
TI  - 2-Styrylindolium based fluorescent probes visualize neurofibrillary tangles in
      Alzheimer's disease.
AB  - We evaluated 2-styrylindolium derivatives (6-11) as novel and selective probes
      for neurofibrillary tangles (NFTs) on brain sections of AD patients. The staining
      experiments indicated that these compounds may bind selectively to NFTs in the
      presence of beta-amyloid (Abeta) plaques. Cell free binding assays confirmed that
      2-[2-[4-(1-pyrrolidinyl)phenyl]ethenyl]-1,3,3-trimethyl-3H-indolium iodide (9)
      and 2-[2-[4-(diethylamino)phenyl]ethenyl]-1-butyl-3,3-dimethyl-3H-indolium iodide
      (11) display excellent affinities to Tau-aggregates (IC(50) values of 5.1 and 1.4
      nM, respectively) in the displacement of Thiazin Red R. These probes have good
      solubility in distilled water and low or no cytotoxicity in zebrafish embryo and
      liver hepatocellular carcinoma cell assays.

PMID- 23127888
TI  - Azabenzthiazole inhibitors of leukotriene A4 hydrolase.
AB  - Previously, benzthiazole containing LTA(4)H inhibitors were discovered that were
      potent (1-3), but were associated with the potential for a hERG liability.
      Utilizing medicinal chemistry first principles (e.g., introducing rigidity,
      lowering cLogD) a new benzthiazole series was designed, congeners of 1-3, which
      led to compounds 7a, 7c, 12a-d which exhibited LTA(4)H IC(50)=3-6 nM and hERG
      Dofetilide Binding IC(50)=8.9-> >10 MUM.

PMID- 23127890
TI  - SAR and in vivo evaluation of 4-aryl-2-aminoalkylpyrimidines as potent and
      selective Janus kinase 2 (JAK2) inhibitors.
AB  - We report the discovery of a series of 4-aryl-2-aminoalkylpyrimidine derivatives
      as potent and selective JAK2 inhibitors. High throughput screening of our in
      house compound library led to the identification of hit 1, from which
      optimization resulted in the discovery of highly potent and selective JAK2
      inhibitors. Advanced lead 10d demonstrated a significant dose-dependent
      pharmacodynamic and antitumor effect in a mouse xenograft model. Based upon the
      desirable profile of 10d (XL019) it was advanced into clinical trials.

PMID- 23127891
TI  - Design, synthesis, and evaluation of resveratrol derivatives as Abeta(1-42)
      aggregation inhibitors, antioxidants, and neuroprotective agents.
AB  - A series of novel resveratrol derivatives were designed, synthesised and
      evaluated as potential therapeutic agents for the treatment of Alzheimer's
      disease. Among these compounds, compound 7l, (E)-5-(4
      (isopropylamino)styryl)benzene-1,3-diol, exhibited potent beta-amyloid
      aggregation inhibition activity, which was confirmed by a ThT fluorescence assay
      (71.65% at 20 MUM) and transmission electron microscopy (TEM). Compound 7l also
      exhibited good antioxidant activity (4.12 Trolox equivalents in an oxygen radical
      absorbance capacity assay and a 37% reduction in reactive oxygen species in cells
      at 10 MUM). The cytotoxicity analysis of compounds 7f, 7i, 7j and 7l indicated
      that these compounds have lower toxicities than resveratrol at 60 MUM.

PMID- 23127892
TI  - A mathematical model for the transmission of Schistosoma japonicum in
      consideration of seasonal water level fluctuations of Poyang Lake in Jiangxi,
      China.
AB  - BACKGROUND: Poyang Lake, the largest fresh water lake in China, is the major
      transmission site of Schistosoma japonicum in China. Epidemics of schistosomiasis
      japonica have threatened the health of residents and stunted social-economic
      development there. OBJECTIVE: This article aims at evaluating the effect of
      various control measures against schistosomiasis: selective mass treatment (ST),
      targeted mass treatment (TT), mass treatment for animal reservoirs (MT), and
      health education (HE), on reduction of the prevalence through simulations based
      on a mathematical model. METHODS: We proposed a mathematical model, which is a
      system of ordinary differential equations for the transmission of S. japonicum
      among humans, bovines, and snails. The model takes into account the seasonal
      variation of the water level of Poyang Lake that is caused by the backflow of the
      Yangtze River and inflow from five small rivers, which influences the
      transmission of S. japonicum. For the purpose of dealing with the age-specific
      prevalence and intensity of infection, the human population was classified into
      four age categories in the model. We carried out several simulations resulting
      from the execution of ST and TT for elementary school children (E Sch), and
      combinations of ST, MT, and HE. RESULTS: The simulations indicated that all of
      the control measures only for humans had a trend of revival after interruption,
      and a combination of ST and MT has a significant effect on reducing human
      infection. Although TT and HE had a significant effect on the prevalence in the E
      Sch group, it had little effect on the overall human population. CONCLUSION: The
      simulations indicate that measures targeted to bovines such as chemotherapy
      besides humans will be vital to eliminate the transmission of S. japonicum in the
      Poyang Lake region. Moreover, it is desirable to improve health education for
      fishermen and herdsmen.

PMID- 23127893
TI  - Transplantation of bone marrow stromal cell-derived neural precursor cells
      ameliorates deficits in a rat model of complete spinal cord transection.
AB  - After severe spinal cord injury, spontaneous functional recovery is limited.
      Numerous studies have demonstrated cell transplantation as a reliable therapeutic
      approach. However, it remains unknown whether grafted neuronal cells could
      replace lost neurons and reconstruct neuronal networks in the injured spinal
      cord. To address this issue, we transplanted bone marrow stromal cell-derived
      neural progenitor cells (BM-NPCs) in a rat model of complete spinal cord
      transection 9 days after the injury. BM-NPCs were induced from bone marrow
      stromal cells (BMSCs) by gene transfer of the Notch-1 intracellular domain
      followed by culturing in the neurosphere method. As reported previously, BM-NPCs
      differentiated into neuronal cells in a highly selective manner in vitro. We
      assessed hind limb movements of the animals weekly for 7 weeks to monitor
      functional recovery after local injection of BM-NPCs to the transected site. To
      test the sensory recovery, we performed functional magnetic resonance imaging
      (fMRI) using electrical stimulation of the hind limbs. In the injured spinal
      cord, transplanted BM-NPCs were confirmed to express neuronal markers 7 weeks
      following the transplantation. Grafted cells successfully extended neurites
      beyond the transected portion of the spinal cord. Adjacent localization of
      synaptophysin and PSD-95 in the transplanted cells suggested synaptic formations.
      These results indicated survival and successful differentiation of BM-NPCs in the
      severely injured spinal cord. Importantly, rats that received BM-NPCs
      demonstrated significant motor recovery when compared to the vehicle injection
      group. Volumes of the fMRI signals in somatosensory cortex were larger in the BM
      NPC-grafted animals. However, neuronal activity was diverse and not confined to
      the original hind limb territory in the somatosensory cortex. Therefore,
      reconstruction of neuronal networks was not clearly confirmed. Our results
      indicated BM-NPCs as an effective method to deliver neuronal lineage cells in a
      severely injured spinal cord. However, reestablishment of neuronal networks in
      completed transected spinal cord was still a challenging task. 

PMID- 23127894
TI  - The fairytale of the GSSG/GSH redox potential.
AB  - BACKGROUND: The term GSSG/GSH redox potential is frequently used to explain redox
      regulation and other biological processes. SCOPE OF REVIEW: The relevance of the
      GSSG/GSH redox potential as driving force of biological processes is critically
      discussed. It is recalled that the concentration ratio of GSSG and GSH reflects
      little else than a steady state, which overwhelmingly results from fast enzymatic
      processes utilizing, degrading or regenerating GSH. MAJOR CONCLUSIONS: A
      biological GSSG/GSH redox potential, as calculated by the Nernst equation, is a
      deduced electrochemical parameter based on direct measurements of GSH and GSSG
      that are often complicated by poorly substantiated assumptions. It is considered
      irrelevant to the steering of any biological process. GSH-utilizing enzymes
      depend on the concentration of GSH, not on [GSH](2), as is predicted by the
      Nernst equation, and are typically not affected by GSSG. Regulatory processes
      involving oxidants and GSH are considered to make use of mechanistic principles
      known for thiol peroxidases which catalyze the oxidation of hydroperoxides by GSH
      by means of an enzyme substitution mechanism involving only bimolecular reaction
      steps. GENERAL SIGNIFICANCE: The negligibly small rate constants of related
      spontaneous reactions as compared with enzyme-catalyzed ones underscore the
      superiority of kinetic parameters over electrochemical or thermodynamic ones for
      an in-depth understanding of GSH-dependent biological phenomena. At best, the
      GSSG/GSH potential might be useful as an analytical tool to disclose disturbances
      in redox metabolism. This article is part of a Special Issue entitled Cellular
      Functions of Glutathione.

PMID- 23127895
TI  - Caesarean section in cases of placenta praevia and accreta.
AB  - In the past decade, the incidence of placenta praevia and placenta accreta has
      increased and seems to be associated with induced labour, termination of
      pregnancy, caesarean section and pregnancy at older age. These factors imply some
      degree of tissue damage, which can modify the decidualisation process, and
      produce excessive vascular remodelling. Placenta praevia and accreta are mainly
      located in the lower segment, a place that predisposes to persistent uterine
      bleeding because of the development of new vessels and because it is a poorly
      contractile area of the uterus. The complexity, determined by tissue destruction,
      newly formed vessels, and vascular invasion of surrounding tissues, warrants
      multi-disciplinary management. When resective procedures are undertaken, a
      suitable plan to tackle surgical problems allows better control of bleeding and
      avoids unnecessary hysterectomies. In cases of placenta accrete, and especially
      when skills or institutional resources are not available, leaving the placenta in
      situ may be the best option until definitive treatment is undertaken.

PMID- 23127896
TI  - Methods of achieving and maintaining an appropriate caesarean section rate.
AB  - Caesarean section rates continue to increase worldwide. The appropriate caesarean
      section rate remains a topic of debate among women and professionals. Evidence
      based medicine has not provided an answer and depends on interpretation of the
      literature. Overall caesarean section rates are unhelpful, and caesarean section
      rates should not be judged in isolation from other outcomes and epidemiological
      characteristics. Better understanding of caesarean section rates, their
      consequences and their benefits will improve care, and enable learning between
      delivery units nationally and internationally. To achieve and maintain an
      appropriate caesarean section rate requires a Multidisciplinary Quality Assurance
      Programme in each delivery unit, recognising caesarean section rates as one of
      many factors that determine quality. Women will always choose the type of
      delivery that seems safest to them and their babies. Professionals need to
      monitor the quality of their practice continuously in a standardised way to
      ensure that women can make the right choice.

PMID- 23127897
TI  - The comprehensibility of health education programs: questionnaire development and
      results in patients with chronic musculoskeletal diseases.
AB  - OBJECTIVE: The objective was to develop a comprehensive questionnaire for
      measuring the patient-perceived comprehensibility of health education programs
      (COHEP questionnaire). According to a conceptual model outlined in the article,
      comprehensibility is considered a context factor of patient health literacy.
      METHODS: A questionnaire study was carried out on N=577 patients with chronic
      musculoskeletal diseases. During inpatient rehabilitation, patients participated
      in standardized, interactive group education programs conducted by clinic
      personnel. Factorial structure, unidimensionality, reliability, fit to the Rasch
      model, and construct validity were tested. RESULTS: The COHEP consists of 30
      items and 4 scales (comprehension-fostering behavior of program trainers,
      transferability to everyday life, comprehensibility of medical information,
      amount of information). All scales are reliable, unidimensional, and meet the
      requirements of the Rasch model. In addition, there are initial indications of
      validity. The descriptive results show that the overall rating of the
      comprehensibility of patient education programs in the German rehabilitation
      system is good, but that there are clear differences between centers. CONCLUSION:
      The COHEP can be used to evaluate health education programs, since it measures an
      important proximal outcome. PRACTICE IMPLICATIONS: An analysis of patient
      perceived comprehensibility can help providers adapt education sessions better to
      the health literacy of patients.

PMID- 23127898
TI  - Bothrops leucurus venom induces nephrotoxicity in the isolated perfused kidney
      and cultured renal tubular epithelia.
AB  - Bites from snake (Bothrops genus) cause local tissue damage and systemic
      complications, which include alterations such as hemostatic system and acute
      renal failure (ARF). Recent studies suggest that ARF pathogenesis in snakebite
      envenomation is multifactorial and involves hemodynamic disturbances, immunologic
      reactions and direct nephrotoxicity. The aim of the work was to investigate the
      effects of the Bothrops leucurus venom (BlV) in the renal perfusion system and in
      cultured renal tubular cells of the type MDCK (Madin-Darby Canine kidney). BlV
      (10 MUg/mL) reduced the perfusion pressure at 90 and 120 min. The renal vascular
      resistance (RVR) decreased at 120 min of perfusion. The effect on urinary flow
      (UF) and glomerular filtration rate (GFR) started 30 min after BlV infusion, was
      transient and returned to normal at 120 min of perfusion. It was also observed a
      decrease on percentual tubular transport of sodium (%TNa(+)) at 120 min and of
      chloride (%TCl(-)) at 60 and 90 min. The treatment with BlV caused decrease in
      cell viability to the lowest concentration tested with an IC(50) of 1.25 MUg/mL.
      Flow cytometry with annexin V and propidium iodide showed that cell death
      occurred predominantly by necrosis. However, a cell death process may involve
      apoptosis in lower concentrations. BlV treatment (1.25 MUg/mL) led to significant
      depolarization of the mitochondrial membrane potential and, indeed, we found an
      increase in the expression of cell death genes in the lower concentrations
      tested. The venom also evoked an increase in the cytosolic Ca(2+) in a
      concentration dependent manner, indicating that Ca(2+) may participate in the
      venom of B. leucurus effect. The characterization of the effects in the isolated
      kidney and renal tubular cells gives strong evidences that the acute renal
      failure induced by this venom is a result of the direct nephrotoxicity which may
      involve the cell death mechanism.

PMID- 23127899
TI  - Epidemiology and clinical effects of hump-nosed pit viper (Genus: Hypnale)
      envenoming in Sri Lanka.
AB  - Hump-nosed pit vipers of Genus Hypnale are the commonest cause of snake bite in
      Sri Lanka. Although there are many reports of local effects, coagulopathy and
      acute kidney injury, it remains unclear how frequent these clinical effects are
      and therefore the medical importance of this snake genus. The genus has been
      recently revised to include Hypnale hypnale from Sri Lanka and Western Ghats of
      Southern India, and the two endemic species to Sri Lanka, Hypnale zara and
      Hypnale nepa. This was a prospective hospital-based clinical study of definite
      Hypnale spp. bites from July 2008 to July 2010 in six Sri Lankan hospitals. There
      were 114 patients included and all snakes were correctly identified by hospital
      staff as Hypnale spp. Of these, 93 snakes were identified as H. hypnale by an
      expert, 16 as H. zara and five as H. nepa. Most bites occurred on the lower limbs
      in the daytime. There was no difference in the clinical effects between the three
      species. Pain and fang marks were present in all patients, 101 had local swelling
      and only 16 (14%) developed extensive local swelling that spread proximally and
      involved more than half of the bitten limb. Systemic symptoms occurred in 18
      patients; four patients had an abnormal 20 min whole blood clotting test and one
      patient developed an acute kidney injury that required haemodialysis. All
      patients were discharged alive with a median length of stay of 2 days. This study
      confirms that hump-nosed viper bites cause only minor effects in most cases.
      Future studies need to undertake formal coagulation studies and identify
      important early indicators of renal impairment.

PMID- 23127900
TI  - Low-level laser therapy using the minimally invasive laser needle system on
      osteoporotic bone in ovariectomized mice.
AB  - This study tested the effectiveness of low-level laser therapy (LLLT) in
      preventing and/or treating osteoporotic trabecular bone. Mice were ovariectomized
      (OVX) to induce osteoporotic bone loss. The tibiae of eight OVX mice were treated
      for 5 days each week for 2 weeks by LLLT (660 nm, 3 J) using a minimally invasive
      laser needle system (MILNS) which is designed to minimize loss of laser energy
      before reaching bone (LASER group). Another eight mice received a sham treatment
      (SHAM group). Structural parameters of trabecular bone were measured with in vivo
      micro-computed tomography images before and after laser treatment. After LLLT for
      2 weeks, the percentage reduction (%R) was significantly lower in BV/TV (bone
      volume fraction) and Tb.N (trabecular number, p<0.05 and p<0.05) and significant
      higher in Tb.Sp (trabecular separation) and SMI (structure model index, p<0.05
      and p<0.05) than in the SHAM group. The %R in BV/TV at sites directly treated by
      LLLT was significantly lower in the LASER group than the SHAM group (p<0.05,
      p<0.05). These results indicated that LLLT using MILNS may be effective for
      preventing and/or treating trabecular bone loss and the effect may be site
      dependent in the same bone.

PMID- 23127901
TI  - Ensemble empirical mode decomposition based feature enhancement of cardio
      signals.
AB  - This paper presents an application of ensemble empirical mode decomposition
      method for enhancement of specific biological signal features. The application
      for two types of cardiological signals is presented in this article. Detection of
      fiducial points is a routine task for analyzing these signals. In a clinical
      situation, cardiological signals are usually corrupted by artifacts and finding
      exact time instances of various fiducial points is a challenge. Filtering
      approach for signal to noise ratio enhancing is traditionally and widely used in
      clinical practice. Methods, based on filtering, however, have serious limitations
      when it is necessary to find compromise between noise suppression and
      preservation of signal features. The proposed method uses ensemble empirical mode
      decomposition in order to suppress noise or enhance specific waves in the signal.
      Performance of the method was estimated by using clinical electrocardiogram and
      impedance cardiogram signals with synthetic baseline-wander, power-line and added
      Gaussian noise. In electrocardiogram application, an average estimation error of
      QRS complex length was 2.06-4.47%, the smallest in comparison to the reference
      methods. In impedance cardiogram application, the proposed method provided the
      highest cross-correlation coefficient between original and de-noised signal in
      comparison to reference methods. When the signal to noise ratio of the input
      signal was -12 dB, the method provided signal to error ratio of 33 dB in this
      case. The proposed method is adaptive to template and signal itself and thus
      could be applied to other non-stationary biological signals.

PMID- 23127902
TI  - Metabolism of soluble rapeseed meal (Brassica rapa L.) protein during incubations
      with buffered bovine rumen contents in vitro.
AB  - Accurate quantitative information on the fate of dietary protein in the rumen is
      central to modern metabolizable protein systems developed to improve the
      efficiency of nitrogen utilization in ruminants. An in vitro method was developed
      to estimate the rate of soluble rapeseed meal (Brassica rapa L.) protein (SRMP)
      degradation. Unlabeled and (15)N-labeled solvent-extracted rapeseed meal were
      incubated alone or as an equal mixture (125 mg of N/L) with buffered rumen
      contents and a mixture of carbohydrates formulated to provide a constant source
      of fermentable energy during the course of all incubations. Incubations were made
      over 0.33, 0.67, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, and 10.0 h. Enrichment
      of (14)N and (15)N isotopes in total N of ammonia (AN), soluble nonammonia
      (SNAN), and insoluble (ISN) fractions liberated during incubations with test
      proteins was determined. A model with 4 pools that accounted for both
      intracellular and extracellular N transformations was used to estimate the rate
      of SRMP degradation. Parameter values used in the model were adjusted based on
      the size of A(14)N, A(15)N, SNA(14)N, SNA(15)N, IS(14)N, and IS(15)N pools,
      measured at different time points during incubations with buffered rumen fluid.
      The mean rate of N degradation for SRMP was estimated at 0.126 (SD 0.0499) h(-1).
      No substantive difference in the rate of protein degradation or microbial protein
      synthesis was observed during incubations of labeled and unlabeled substrates
      with rumen fluid. In conclusion, combined use of data from incubations of
      unlabeled and (15)N-labeled rapeseed protein with buffered rumen inoculum
      provided sufficient information to allow for estimation of parameter values in a
      complex dynamic model of soluble protein degradation. Results indicate the
      potential of the technique to evaluate the degradability of SNAN of other dietary
      protein sources and implicate ruminal escape of soluble rapeseed protein as an
      important source of amino acids in ruminants.

PMID- 23127903
TI  - Methods to approximate reliabilities in single-step genomic evaluation.
AB  - Reliability of predictions from single-step genomic BLUP (ssGBLUP) can be
      calculated by matrix inversion, but that is not feasible for large data sets. Two
      methods of approximating reliability were developed based on the decomposition of
      a function of reliability into contributions from records, pedigrees, and
      genotypes. Those contributions can be expressed in record or daughter
      equivalents. The first approximation method involved inversion of a matrix that
      contains inverses of the genomic relationship matrix and the pedigree
      relationship matrix for genotyped animals. The second approximation method
      involved only the diagonal elements of those inverses. The 2 approximation
      methods were tested with a simulated data set. The correlations between ssGBLUP
      and approximated contributions from genomic information were 0.92 for the first
      approximation method and 0.56 for the second approximation method; contributions
      were inflated by 62 and 258%, respectively. The respective correlations for
      reliabilities were 0.98 and 0.72. After empirical correction for inflation, those
      correlations increased to 0.99 and 0.89. Approximations of reliabilities of
      predictions by ssGBLUP are accurate and computationally feasible for populations
      with up to 100,000 genotyped animals. A critical part of the approximations is
      quality control of information from single nucleotide polymorphisms and proper
      scaling of the genomic relationship matrix.

PMID- 23127904
TI  - Variation in fat mobilization during early lactation differently affects feed
      intake, body condition, and lipid and glucose metabolism in high-yielding dairy
      cows.
AB  - Fat mobilization to meet energy requirements during early lactation is inevitable
      because of insufficient feed intake, but differs greatly among high-yielding
      dairy cows. Therefore, we studied milk production, feed intake, and body
      condition as well as metabolic and endocrine changes in high-yielding dairy cows
      to identify variable strategies in metabolic and endocrine adaptation to overcome
      postpartum metabolic load attributable to milk production. Cows used in this
      study varied in fat mobilization around calving, as classified by mean total
      liver fat concentrations (LFC) postpartum. German Holstein cows (n=27) were
      studied from dry off until d 63 postpartum in their third lactation. All cows
      were fed the same total mixed rations ad libitum during the dry period and
      lactation. Plasma concentrations of metabolites and hormones were measured in
      blood samples taken at d 56, 28, 15, and 5 before expected calving and at d 1 and
      once weekly up to d 63 postpartum. Liver biopsies were taken on d 56 and 15
      before calving, and on d 1, 14, 28, and 49 postpartum to measure LFC and glycogen
      concentrations. Cows were grouped accordingly to mean total LFC on d 1, 14, and
      28 in high, medium, and low fat-mobilizing cows. Mean LFC (+/-SEM) differed among
      groups and were 351+/-14, 250+/-10, and 159+/-9 mg/g of dry matter for high,
      medium, and low fat-mobilizing cows, respectively, whereas hepatic glycogen
      concentrations postpartum were the highest in low fat-mobilizing cows. Cows in
      the low group showed the highest dry matter intake and the least negative energy
      balance postpartum, but energy-corrected milk yield was similar among groups. The
      decrease in body weight postpartum was greatest in high fat-mobilizing cows, but
      the decrease in backfat thickness was greatest in medium fat-mobilizing cows.
      Plasma concentrations of nonesterified fatty acids and beta-hydroxybutyrate were
      highest around calving in high fat-mobilizing cows. Plasma triglycerides were
      highest in the medium group and plasma cholesterol concentrations were lowest in
      the high group at calving. During early lactation, the decrease in plasma glucose
      concentrations was greatest in the high group, and plasma insulin concentrations
      postpartum were highest in the low group. The revised quantitative insulin
      sensitivity check index values decreased during the transition period and
      postpartum, and were highest in the medium group. Plasma cortisol concentrations
      during the transition period and postpartum period and plasma leptin
      concentrations were highest in the medium group. In conclusion, cows adapted
      differently to the metabolic load and used variable strategies for homeorhetic
      regulation of milk production. Differences in fat mobilization were part of these
      strategies and contributed to the individual adaptation of energy metabolism to
      milk production.

PMID- 23127905
TI  - Application of Bayesian least absolute shrinkage and selection operator (LASSO)
      and BayesCpi methods for genomic selection in French Holstein and Montbeliarde
      breeds.
AB  - Recently, the amount of available single nucleotide polymorphism (SNP) marker
      data has considerably increased in dairy cattle breeds, both for research
      purposes and for application in commercial breeding and selection programs.
      Bayesian methods are currently used in the genomic evaluation of dairy cattle to
      handle very large sets of explanatory variables with a limited number of
      observations. In this study, we applied 2 bayesian methods, BayesCpi and bayesian
      least absolute shrinkage and selection operator (LASSO), to 2 genotyped and
      phenotyped reference populations consisting of 3,940 Holstein bulls and 1,172
      Montbeliarde bulls with approximately 40,000 polymorphic SNP. We compared the
      accuracy of the bayesian methods for the prediction of 3 traits (milk yield, fat
      content, and conception rate) with pedigree-based BLUP, genomic BLUP, partial
      least squares (PLS) regression, and sparse PLS regression, a variable selection
      PLS variant. The results showed that the correlations between observed and
      predicted phenotypes were similar in BayesCpi (including or not pedigree
      information) and bayesian LASSO for most of the traits and whatever the breed. In
      the Holstein breed, bayesian methods led to higher correlations than other
      approaches for fat content and were similar to genomic BLUP for milk yield and to
      genomic BLUP and PLS regression for the conception rate. In the Montbeliarde
      breed, no method dominated the others, except BayesCpi for fat content. The
      better performances of the bayesian methods for fat content in Holstein and
      Montbeliarde breeds are probably due to the effect of the DGAT1 gene. The SNP
      identified by the BayesCpi, bayesian LASSO, and sparse PLS regression methods,
      based on their effect on the different traits of interest, were located at almost
      the same position on the genome. As the bayesian methods resulted in regressions
      of direct genomic values on daughter trait deviations closer to 1 than for the
      other methods tested in this study, bayesian methods are suggested for genomic
      evaluations of French dairy cattle.

PMID- 23127906
TI  - Genetic correlation between composition of bovine milk fat in winter and summer,
      and DGAT1 and SCD1 by season interactions.
AB  - Milk fat composition shows substantial seasonal variation, most of which is
      probably caused by differences in the feeding of dairy cows. The present study
      aimed to know whether milk fat composition in winter is genetically the same
      trait as milk fat composition in summer. For this purpose, we estimated
      heritabilities, genetic correlations, effects of acyl-coenzyme A:diacylglycerol
      acyltransferase 1 (DGAT1) K232A, and stearoyl-coenzyme A desaturase 1 (SCD1)
      A293V polymorphisms for milk fat composition in winter and summer, and tested for
      genotype by season interactions of DGAT1 K232A and SCD1 A293V polymorphisms. Milk
      samples were obtained from 2,001 first-lactation Dutch Holstein-Friesian cows,
      most with records in both winter and summer. Summer milk contained higher amounts
      of unsaturated fatty acids (FA) and lower amounts of saturated FA compared with
      winter milk. Heritability estimates were comparable between seasons: moderate to
      high for short- and medium-chain FA (0.33 to 0.74) and moderate for long-chain FA
      (0.19 to 0.43) in both seasons. Genetic correlations between winter and summer
      milk were high, indicating that milk fat composition in winter and in summer can
      largely be considered as genetically the same trait. Effects of DGAT1 K232A and
      SCD1 A293V polymorphisms were similar across seasons for most FA. Allele DGAT1
      232A in winter as well as in summer milk samples was negatively associated with
      most FA with less than 18 carbons, saturated FA, saturated FA to unsaturated FA
      ratio, and C10 to C16 unsaturation indices, and was positively associated with
      C14:0, unsaturated C18, unsaturated FA, and C18 and conjugated linoleic acid
      unsaturation indices. Allele SCD1 293V in winter as well as in summer milk
      samples was negatively associated with C18:0, C10:1 to cis-9 C14:1, trans-11
      C18:1, and C10 to C14 unsaturation indices, and positively associated with C8:0
      to C14:0, cis-9 C16:1, and C16 to conjugated linoleic acid unsaturation indices.
      In addition, significant DGAT1 K232A by season interaction was found for some FA
      and SCD1 A293V by season interaction was only found for trans-11 C18:1. These
      interactions were due to scaling of genotype effects.

PMID- 23127907
TI  - Effect of farming system and cheesemaking technology on the physicochemical
      characteristics, fatty acid profile, and sensory properties of Caciocavallo
      Palermitano cheese.
AB  - Caciocavallo Palermitano is a typical stretched-curd cheese that has been
      produced over the centuries in Sicily according to traditional cheesemaking
      technology and using raw milk from autochthonous cow breeds reared at pasture.
      The objective of this experiment was to evaluate the effects of the farming
      system and processing technology on the characteristics of Caciocavallo
      Palermitano cheese, with particular regard to the fatty acid profile. The farming
      system was either extensive, using autochthonous cows fed a pasture-based diet,
      or intensive, with specialized dairy cow breeds fed mainly hay and concentrate.
      The cheese-processing technology was either artisanal, using traditional wooden
      tools and endemic lactic bacteria, or advanced, using modern steel equipment and
      selected lactic bacteria. Twelve Caciocavallo Palermitano cheeses, 3 from each of
      the 4 experimental theses (2 farming systems * 2 cheesemaking technologies), were
      obtained and aged for 1, 30, 60, and 120 d. Milk of origin and cheeses were
      analyzed for the main chemical and rheological parameters. Fatty acids were
      methylated in lyophilized cheese and analyzed by gas chromatography. Sensory
      analysis was carried out by trained panelists. The PROC GLM of SAS 9.1.2 (SAS
      Institute Inc., Cary, NY) was used for the statistical analysis. The physical,
      chemical, and sensory characteristics of Caciocavallo Palermitano cheese were
      influenced more by the farming system than by the cheesemaking technology.
      Compared with cheese produced through intensive farming, cheese from extensive
      farming was richer in polyunsaturated, n-3, and odd- and branched-chain fatty
      acids, as well as in conjugated linoleic acid (cis-9,trans-11 C18:2), with
      accompanying improved human health benefits. The cheesemaking technology produced
      variation in the evolution of proteolysis during aging, due presumably to the
      different active microflora, which influenced the sensory profile of the
      resulting cheese. Indeed, cheese produced by artisanal manufacturing was
      described as less "bitter" and more "piquant" than cheese produced through the
      advanced process.

PMID- 23127908
TI  - Technical note: Determination of preanalysis storage temperature and time
      allowances for ex vivo innate immune responses.
AB  - Evaluation of ex vivo innate immune responses requires the transport of blood to
      a laboratory for analyses. Storage temperature and duration are highly variable
      in the published literature. The objective of the present study was to establish
      recommended storage temperature and duration for blood before analysis of several
      ex vivo innate immune responses in vitro. Peripheral blood was collected from 8
      clinically healthy, 12-mo-old Holstein heifers and stored either on ice or at
      ambient temperature for 1.5, 3.5, 5.5, 7.5, 9.5, and 24 h before conducting
      analyses for lipopolysaccharide stimulated whole blood tumor necrosis factor
      alpha (TNF-alpha) secretion, neutrophil L-selectin expression, and neutrophil
      phagocytic and oxidative burst capacities when exposed to an Escherichia coli. L
      Selectin expression was greater in neutrophils stored on ice as early as 1.5 h
      after blood collection. In addition, when neutrophils were stored on ice, L
      selectin expression at 24 h was not different from that at 1.5 h after blood
      collection. Measures of innate immune cell function, including whole blood TNF
      alpha secretion and neutrophil phagocytic and oxidative burst abilities, were
      decreased in blood stored on ice. Both TNF-alpha secretion and neutrophil
      oxidative burst intensity did not differ at 24 h compared with 1.5 h after blood
      collection when blood was stored at ambient temperatures. These data indicate
      that both storage temperature and duration influence measures of innate immune
      responses. Therefore, storage durations should be minimized and storage protocols
      kept consistent to reduce the influences of storage conditions on experimental
      results.

PMID- 23127909
TI  - Effect of protein supplementation on milk production and metabolism of dairy cows
      grazing tropical grass.
AB  - The objectives of this study were to determine if midlactation dairy cows (Bos
      taurus L.) grazing intensively managed elephantgrass would have their protein
      requirement met exclusively with the pasture and an energy concentrate, making
      the use of protein ingredients unnecessary, as well as to determine the dietary
      crude protein (CP) content that would optimize the efficiency of N utilization
      (ENU). Thirty-three Holstein and crossbred (Holstein * Jersey) midlactation dairy
      cows, producing approximately 20 kg/d, were grouped within breed into 11 blocks
      according to milk yield and days in milk. Within blocks, cows were randomly
      assigned to 1 of 3 treatments and remained in the study for 11 wk. The control
      treatment contained only finely ground corn, minerals, and vitamins, and it was
      formulated to be 8.7% CP. Two higher levels of CP (formulated to be 13.4 and
      18.1%) were achieved by replacing corn with solvent-extracted soybean meal
      (SSBM). Pasture was fertilized with 50 kg of N/ha after each grazing cycle and
      averaged 18.5% CP (dry matter basis). No differences were observed in milk yield
      or milk fat, protein, and casein content or casein yield. In addition, pasture
      intake was not different among treatments. Milk urea N increased linearly as the
      concentrate CP content increased. Cows fed the 8.7% CP concentrate had higher
      ENU. In another experiment, 4 ruminally cannulated Holstein dry cows were used in
      a metabolism trial designed in a 4*4 Latin square. Cows were fed the same
      treatments described as well as a fourth treatment with 13.4% CP in the
      concentrate, in which urea replaced SSBM as the main N source. Ruminal volatile
      fatty acid concentration and microbial synthesis were not affected by levels or
      sources of N in the concentrate. Ruminal NH(3)N content increased as the
      concentrate CP content increased. Inclusion of SSBM in the concentrate did not
      increase production and decreased the ENU of midlactation dairy cows grazing on
      tropical forage. Supplementation of an 8.7% CP concentrate, resulting in a diet
      with CP levels between 15.3 and 15.7% of dry matter, was sufficient to meet the
      protein requirements of such milk production, with the highest ENU (18.4%).

PMID- 23127910
TI  - Starch plus sunflower oil addition to the diet of dry dairy cows results in a
      trans-11 to trans-10 shift of biohydrogenation.
AB  - Trans fatty acids (FA), exhibit different biological properties. Among them, cis
      9,trans-11 conjugated linoleic acid has some interesting putative health
      properties, whereas trans-10,cis-12 conjugated linoleic acid has negative effects
      on cow milk fat production and would negatively affect human health. In high
      yielding dairy cows, a shift from trans-11 to trans-10 pathway of
      biohydrogenation (BH) can occur in the rumen of cows receiving high-concentrate
      diets, especially when the diet is supplemented with unsaturated fat sources. To
      study this shift, 4 rumen-fistulated nonlactating Holstein cows were assigned to
      a 4*4 Latin square design with 4 different diets during 4 periods. Cows received
      12 kg of dry matter per day of 4 diets based on corn silage during 4 successive
      periods: a control diet (22% starch, <3% crude fat on DM basis), a high-starch
      diet supplemented with wheat plus barley (35% starch, <3% crude fat), a sunflower
      oil diet supplemented with 5% of sunflower oil (20% starch, 7.6% crude fat), and
      a high-starch plus sunflower oil diet (33% starch, 7.3% crude fat). Five hours
      after feeding, proportions of trans-11 BH isomers greatly increased in the rumen
      content with the addition of sunflower oil, without change in ruminal pH compared
      with the control diet. Addition of starch to the control diet had no effect on BH
      pathways but decreased ruminal pH. The addition of a large amount of starch in
      association with sunflower oil increased trans-10 FA at the expense of trans-11
      FA in the rumen content, revealing a trans-11 to trans-10 shift. Interestingly,
      with this latter diet, ruminal pH did not change compared with a single addition
      of starch. This trans-11 to trans-10 shift occurred progressively, after a
      decrease in the proportion of trans-11 FA in the rumen, suggesting that this
      shift could result from a dysbiosis in the rumen in favor of trans-10-producing
      bacteria at the expense of those producing trans-11 or a modification of
      bacterial activities.

PMID- 23127911
TI  - Comparison of genomic and antimicrobial resistance features of latex
      agglutination test-positive and latex agglutination test-negative Staphylococcus
      aureus isolates causing bovine mastitis.
AB  - The dairy industry suffers massive economic losses due to staphylococcal mastitis
      in cattle. The Staphaureux latex agglutination test (Oxoid, Basel, Switzerland)
      was reported to lead to negative results in 54% of bovine Staphylococcus aureus
      strains, and latex-negative strains are thought to be less virulent than
      Staphaurex latex-positive strains. However, comparative information on virulence
      and resistance profiles of these 2 groups of Staph. aureus is scarce. Our
      objective was to associate the latex agglutination phenotype of Staph. aureus
      strains isolated from bovine mastitis milk with data on clonal complexes,
      virulence genes, and antibiotic resistance to (1) determine the virulence
      profiles of the Staphaureux test positive and Staphaurex test negative groups,
      and (2) provide data needed to improve treatment of bovine mastitis and to
      identify potential vaccine targets. Seventy-eight Staph. aureus strains isolated
      from 78 cows on 57 Swiss farms were characterized. Latex agglutination was tested
      by Staphaureux kit, and resistance profiles were generated by disk diffusion. A
      DNA microarray was used to assign clonal complexes (CC) and to determine
      virulence and resistance gene profiles. By the Staphaureux test, 49% of the
      isolates were latex-positive and 51% were latex-negative. All latex-negative
      strains were assigned to CC151, whereas latex-positive strains were assigned to
      various clonal complexes, including CC97 (n=16), CC8 (n=10), CC479 (n=5), CC20
      (n=4), CC7 (n=1), CC9 (n=1), and CC45 (n=1). Although the latex-negative isolates
      were susceptible to all antimicrobial agents tested, 24% of latex-positive
      isolates were classified as intermediate with regard to cefalexin-kanamycin and
      13% were resistant to both ampicillin and penicillin. Microarray profiles of
      latex-negative isolates were highly similar, but differed largely from those of
      latex-positive isolates. Although the latex-negative group lacked several
      enterotoxin genes and sak, it exhibited significantly higher prevalence rates of
      genes encoding enterotoxin C, toxic shock syndrome toxin, and leukocidins
      (lukM/lukF-P83, lukD). Our findings suggest that latex-negative isolates
      represent a group of closely related strains with specific resistance and
      virulence gene patterns.

PMID- 23127912
TI  - Genetic analyses of fertility and predictor traits in Holstein herds with low and
      high mean calving intervals and in Jersey herds.
AB  - Genetic parameters were estimated with the aim of identifying useful predictor
      traits for the genetic evaluation of fertility. For this study, data included
      calving interval (CI), days from calving to first service (CFS), pregnancy
      diagnosis, lactation length (LL), daily milk yield close to 90 d of lactation
      (milk yield), and survival to second lactation on Australian Holstein and Jersey
      cows. The effect of level of fertility, measured here as CI, on correlations
      among traits was investigated by dividing the Holstein herds into those that
      managed short CI (proxy for seasonal-calving herds) and long CI (proxy for herds
      that practice extended lactations). In all cases, genetic correlations of CI with
      CFS, pregnancy, and LL were high (>0.7). Genetic correlations between fertility
      and predictor traits were generally similar in the 2 Holstein herd groups and in
      Jerseys. However, some differences in both the direction and strength of
      correlations were observed. In Jerseys, the genetic correlation between CI and
      survival was positive, but in Holstein herds, this correlation was negative.
      Particularly in low mean CI herds, the correlation suggests that cows with a
      genetic potential for longer CI were more likely to be culled. The genetic
      correlation of CI with survival was intermediate in high mean CI Holstein herds.
      Furthermore, Jersey cows with a high genetic potential for milk yield had a
      higher chance of surviving than those with low genetic potential. In contrast,
      the genetic correlation between milk yield and survival in low mean CI Holstein
      herds was near zero. The high genetic correlation between CI and LL suggests that
      LL could be used as proxy for CI in cows that do not calve again. Although the
      phenotypic variance for CI in high mean CI herds was nearly twice that in Jerseys
      and low mean CI herds, we found no bull reranking for CI due to having daughters
      in low or high mean CI herds. However, the ranges in estimated breeding values
      (EBV) were narrower in low mean CI herds than in high mean CI herds. The genetic
      trend in cows and bulls showed that CI EBV were increasing by 0.3 to 0.8 d/yr in
      both Holstein and Jersey. Phenotypically, CI was increasing by 2 d/yr in high
      mean CI Holstein herds and by 1 d/yr in Jersey and low mean CI Holstein herds.
      However, in recent years, both phenotypic and genetic trends have stabilized. In
      summary, if the main trait for genetic evaluation of fertility is CI, predictor
      traits such as milk yield, survival, LL, and other fertility traits can be used
      in joint analyses to increase reliability of bull EBV. If the genetic evaluation
      is to be carried out simultaneously for Holstein and Jersey using the same
      variance-covariance matrix, survival should not be used as a predictor because
      its correlation with CI is different in Jersey than in Holstein. On the other
      hand, LL could be used instead of CI for cows that do not calve again in both
      breeds and herd groups.

PMID- 23127913
TI  - Short communication: Intraoperator repeatability and interoperator
      reproducibility of devices measuring teat dimensions in dairy cows.
AB  - Various methods have been applied to measure teat dimensions. However, the
      accuracy and precision needed to obtain reliable results are often poor or have
      not yet been investigated. To determine the precision of the ruler, the caliper,
      and a recently developed 2-dimensional (2D) vision-based measuring device under
      field conditions, for respectively teat length, teat diameter, and both teat
      length and diameter, 2 experiments were conducted in which the consistency of
      measurements within operators (repeatability) and between operators
      (reproducibility) was tested. In addition, the agreement of the 2D device with
      the ruler and the caliper was studied. Although the ruler and the 2D device
      poorly agreed, both methods were precise in measuring teat length when the
      operators had experience in working with cows. The caliper was repeatable in
      measuring teat diameter, but was not reproducible. The 2D device was also
      repeatable in measuring teat diameter, and reproducible when the operators had
      experience with the device. The methods had poor agreement, most likely due to
      the operator-dependent pressure applied by the caliper. Because the 2D device has
      the advantage of measuring both teat length and teat diameters in a single
      measurement and is accurate and practical, this method allows efficient and fast
      collection of data on a large scale for various applications.

PMID- 23127914
TI  - Short communication: Bacteriocin KC24 produced by Lactococcus lactis KC24 from
      kimchi and its antilisterial effect in UHT milk.
AB  - The severity of Listeria monocytogenes infections emphasizes the need for
      prevention or elimination of the pathogen from dairy products. Lactococcus lactis
      KC24, isolated from kimchi, exhibited an antimicrobial effect against food
      pathogens, including L. monocytogenes ATCC 15313. Lactococcus lactis KC24 was
      cultured in a 5-L jar fermenter at 35 degrees C, and bacteriocin activity was
      maximal at 4 h of incubation and persisted for 20 h. Bacteriocin KC24 was
      inactivated by protease XIV, indicating that it has a proteinaceous nature.
      Bacteriocin activity was maintained at pH 3.0 to 9.0 and at temperatures of 50 to
      121 degrees C. The mode of inhibition against L. monocytogenes ATCC 15313 was
      shown to involve a bactericidal effect by treatment with 100 and 200 arbitrary
      units (AU)/mL of bacteriocin KC24. To test the activity of bacteriocin KC24 in a
      food product, bacteriocin KC24 and nisin (100 and 200 AU/mL) with 4 log cfu/mL of
      a mixed culture of L. monocytogenes (ATCC 15313, ScottA, H7962, and H7762) were
      applied to UHT milk. Compared with the control, treatment with bacteriocin KC24
      completely inhibited the growth of L. monocytogenes and resulted in no detectable
      L. monocytogenes after 14 d at 4 degrees C, whereas nisin moderately inhibited L.
      monocytogenes, resulting in a final concentration after 14 d at 4 degrees C
      higher than the initial inoculum. Bacteriocin KC24 may prove useful in improving
      the safety of dairy products.

PMID- 23127916
TI  - Polymorphisms in OCTN1 and OCTN2 transporters genes are associated with prolonged
      time to progression in unresectable gastrointestinal stromal tumours treated with
      imatinib therapy.
AB  - The two basic mainstays of gastrointestinal stromal tumours (GIST) treatment are
      surgery and imatinib, a selective tyrosine kinase inhibitor that allows achieving
      a stable or responding disease in about 80% of patients with
      unresectable/metastatic GIST. Response to imatinib mainly depends from KIT and
      PDGFRalpha mutational status. Nevertheless, some patients with a potentially
      responsive genotype do not respond, and others develop a pattern of resistance to
      imatinib which is not associated with secondary mutations. This emphasizes the
      presence of mechanisms of resistance other than the receptor-related genotype,
      and the need of biological predictors to select the optimal therapeutic strategy,
      particularly now that other potent inhibitors are available. We investigated a
      panel of 31 polymorphisms in 11 genes, potentially associated with the
      pharmacogenetics of imatinib, in a group of 54 unresectable/metastatic GISTs
      treated with imatinib 400mg daily as first line therapy. Included in this
      analysis were polymorphisms in the transporters' family SLC22, SLCO, ABC, and in
      the metabolizing genes CYP-3A4 and -3A5. Time to progression was significantly
      improved in presence of the C allele in SLC22A4 (OCTN1 rs1050152), and the two
      minor alleles (G) in SLC22A5 (OCTN2 rs2631367 and rs2631372). Importantly,
      multivariate analysis, adjusting for age, gender, KIT/PDGFRalpha mutational
      status, and tumour size, revealed that all the three genotypes maintained
      independent predictive significance. In conclusion, in this study we showed that
      SLC22A4 and SLC22A5 genotypes may be an important predictor of time to
      progression in GIST patients receiving imatinib therapy. Further investigations
      are required in an attempt to further personalize GIST therapy.

PMID- 23127917
TI  - Angiotensin-(1-7) modulates renin-angiotensin system associated with reducing
      oxidative stress and attenuating neuronal apoptosis in the brain of hypertensive
      rats.
AB  - Angiotensin-(1-7) [Ang-(1-7)] has beneficial effects against hypertension-induced
      damage in heart and kidney, but its effects in brain are not clear as yet. The
      present study aimed to investigate the protective effects of Ang-(1-7) on the
      physiopathologic changes caused by hypertension in brain of spontaneously
      hypertensive rats (SHRs). Wistar-Kyoto rats received intracerebroventricular
      (I.C.V.) infusion of artificial cerebrospinal fluid (aCSF) while SHRs received
      I.C.V. infusion of Ang-(1-7), Mas receptor antagonist A-779 and aCSF for 4 weeks.
      Brain tissues were collected and analyzed by western blot, enzyme immunoassay,
      spectrophotometric assays and terminal deoxynucleotidyl transferase-mediated dUTP
      end-labeling (TUNEL) staining. Our study showed that infusion of Ang-(1-7) for 4
      weeks significantly reduced the expression of Angiotensin II and Angiotensin II
      type 1 receptors in SHR brain. Additionally, it decreased the levels of
      malondialdehyde and elevated total superoxide dismutase activity, which was
      accompanied by reductions of NADPH oxidase subunit gp91(phox) and inducible
      nitric oxide synthase in the brain of SHR. The increases of the percentage of
      TUNEL-positive neurons and Bax to Bcl-2 ratio in SHR brain were also attenuated
      by Ang-(1-7). The anti-oxidative and anti-apoptosis effects of Ang-(1-7) are
      independent of blood pressure reduction and can be partially abolished by A-779.
      These findings suggest that chronic treatment with Ang-(1-7) is beneficial to
      attenuate hypertension-induced physiopathologic changes in brain and may be
      helpful to prevent hypertension-related cerebrovascular diseases.

PMID- 23127915
TI  - Alterations in endocannabinoid tone following chemotherapy-induced peripheral
      neuropathy: effects of endocannabinoid deactivation inhibitors targeting fatty
      acid amide hydrolase and monoacylglycerol lipase in comparison to reference
      analgesics following cisplatin treatment.
AB  - Cisplatin, a platinum-derived chemotherapeutic agent, produces mechanical and
      coldallodynia reminiscent of chemotherapy-induced neuropathy in humans. The
      endocannabinoid system represents a novel target for analgesic drug development.
      The endocannabinoid signaling system consists of endocannabinoids (e.g.
      anandamide (AEA) and 2-arachidonoylglycerol (2-AG)), cannabinoid receptors (e.g.
      CB(1) and CB(2)) and the enzymes controlling endocannabinoid synthesis and
      degradation. AEA is hydrolyzed by fatty-acid amide hydrolase (FAAH) whereas 2-AG
      is hydrolyzed primarily by monoacylglycerol lipase (MGL). We compared effects of
      brain permeant (URB597) and impermeant (URB937) inhibitors of FAAH with an
      irreversible inhibitor of MGL (JZL184) on cisplatin-evoked behavioral
      hypersensitivities. Endocannabinoid modulators were compared with agents used
      clinically to treat neuropathy (i.e. the opioid analgesic morphine, the
      anticonvulsant gabapentin and the tricyclic antidepressant amitriptyline).
      Cisplatin produced robust mechanical and cold allodynia but did not alter
      responsiveness to heat. After neuropathy was fully established, groups received
      acute intraperitoneal (i.p.) injections of vehicle, amitriptyline (30 mg/kg),
      gabapentin (100 mg/kg), morphine (6 mg/kg), URB597 (0.1 or 1 mg/kg), URB937 (0.1
      or 1 mg/kg) or JZL184 (1, 3 or 8 mg/kg). Pharmacological specificity was assessed
      by coadministering each endocannabinoid modulator with either a CB(1) (AM251 3
      mg/kg), CB(2) (AM630 3 mg/kg), TRPV1 (AMG9810 3 mg/kg) or TRPA1 (HC030031 8
      mg/kg) antagonist. Effects of cisplatin on endocannabinoid levels and
      transcription of receptors (CB(1), CB(2), TRPV1, TRPA1) and enzymes (FAAH, MGL)
      linked to the endocannabinoid system were also assessed. URB597, URB937, JZL184
      and morphine reversed cisplatin-evoked mechanical and cold allodynia to pre
      cisplatin levels. By contrast, gabapentin only partially reversed the observed
      allodynia while amitriptyline, administered acutely, was ineffective. CB(1) or
      CB(2) antagonists completely blocked the anti-allodynic effects of both FAAH
      (URB597, URB937) and MGL (JZL184) inhibitors to mechanical and cold stimulation.
      By contrast, the TRPV1 antagonist AMG9810 blocked the anti-allodynic efficacy of
      both FAAH inhibitors, but not the MGL inhibitor. By contrast, the TRPA1
      antagonist HC30031 did not attenuate anti-allodynic efficacy of any
      endocannabinoid modulator. When the levels of endocannabinoids were examined,
      cisplatin increased both anandamide (AEA) and 2-arachidonoylglycerol (2-AG)
      levels in the lumbar spinal cord and decreased 2-AG levels (but not AEA) in
      dorsal hind paw skin. RT-PCR showed that mRNA for FAAH, but not other markers,
      was upregulated by cisplatin treatment in lumbar spinal cord. The present studies
      demonstrate that cisplatin alters endocannabinoid tone and that inhibition of
      endocannabinoid hydrolysis alleviates chemotherapy-induced mechanical and cold
      allodynia. The anti-allodynic effects of FAAH and MGL inhibitors are mediated by
      CB(1) and CB(2) cannabinoid receptors, whereas TRPV1, but not TRPA1, -dependent
      mechanisms contribute to the anti-allodynic efficacy of FAAH (but not MGL)
      inhibitors. Strikingly, endocannabinoid modulators potently suppressed cisplatin
      evoked allodynia with a rapid onset and showed efficacy that equaled or exceeded
      that of major classes of anti-neuropathic pain medications used clinically. Thus,
      inhibition of endocannabinoid hydrolysis, via FAAH or MGL inhibitors, represents
      an efficacious pharmacological approach for suppressing chemotherapy-induced
      neuropathic pain.

PMID- 23127918
TI  - Experimental study of interfacial fracture toughness in a SiN(x)/PMMA barrier
      film.
AB  - Organic/inorganic multilayer barrier films play an important role in the
      semihermetic packaging of organic electronic devices. With the rise in use of
      flexible organic electronics, there exists the potential for mechanical failure
      due to the loss of adhesion/cohesion when exposed to harsh environmental
      operating conditions. Although barrier performance has been the predominant
      metric for evaluating these encapsulation films, interfacial adhesion between the
      organic/inorganic barrier films and factors that influence their mechanical
      strength and reliability has received little attention. In this work, we present
      the interfacial fracture toughness of a model organic/inorganic multilayer
      barrier (SiN(x)-PMMA). Data from four point bending (FPB) tests showed that
      adhesive failure occurred between the SiN(x) and PMMA, and that the adhesion
      increased from 4.8 to 10 J/m(2) by using a variety of chemical treatments to vary
      the surface energy at the interface. Moreover, the adhesion strength increased to
      28 J/m(2) by creating strong covalent bonds at the interface. Overall, three
      factors were found to have the greatest impact on the interfacial fracture
      toughness which were (a) increasing the polar component of the surface energy,
      (b) creating strong covalent bonds at the organic/inorganic interface, and (c) by
      increasing the plastic zone size at the crack tip by increasing the thickness of
      the PMMA layer.

PMID- 23127919
TI  - The effects of vaccination on serum hormone concentrations and conception rates
      in synchronized naive beef heifers.
AB  - Crossbred beef heifers (N = 59) were vaccinated at the time of
      synchronization/breeding with either a commercially available bovine herpesvirus
      type 1 modified live virus (MLV) (one dose) or inactivated virus vaccine (one or
      two doses). The estrus cycle was synchronized at vaccination and heifers were
      artificially inseminated 8 days (one dose) or 36 days (two dose) after initial
      vaccination. Pregnancy rates were greater for control heifers (90%; P = 0.02) and
      heifers given the inactivated virus vaccine (one dose: 86%; P = 0.08; or two:
      90%; P < 0.01) than those given the MLV vaccine (48%). No control heifers
      experienced an abnormal estrous cycle, whereas only two (two dose; 2/21) and one
      (one dose; 1/7) heifers in the inactive virus groups had abnormal estrous cycles
      and were similar to control (P > 0.10). Heifers given the MLV vaccine had a
      greater (P = 0.02) percentage of abnormal estrous cycles (38%; 8/21) compared
      with the control and inactivated groups. Of the heifers with an abnormal estrous
      cycle, 100% of heifers given the inactivated vaccine (one or two dose) conceived
      at their return estrus, whereas only 38% of heifers given the MLV vaccine
      conceived at their return estrus (P > 0.10). During the synchronization period,
      concentrations of estrogen were greater (P < 0.01) in the control and the two
      dose inactivated group compared with the MLV group. After AI, progesterone
      concentrations were greater (P < 0.01) in control heifers compared with the
      inactivated and MLV groups, but were similar (P >= 0.18) between the inactivated
      and MLV groups. Therefore, naive heifers vaccinated with the inactivated vaccine
      were less likely to have an abnormal estrous cycle and had significantly higher
      pregnancy rates compared with heifers vaccinated with the MLV vaccine. In
      summary, vaccination of naive heifers with an MLV vaccine at the start of a fixed
      time AI protocol had a negative effect on pregnancy success.

PMID- 23127920
TI  - Ovarian responses and pregnancy rate with previously used intravaginal
      progesterone releasing devices for fixed-time artificial insemination in sheep.
AB  - The objective was to determine serum progesterone concentrations, ovarian
      responses, and pregnancy rate in sheep inseminated following a short-term
      protocol (6 days of treatment) with a previously used controlled internal drug
      release-G (CIDR-G) device. In experiment 1, 30 ewes were put on a short-term
      protocol using a CIDR-G of first use (new devices, N = 10), second use
      (previously used for 6 days, N = 10), or third use (previously used twice for 6
      days, N = 10). All ewes were given prostaglandin F(2alpha) (10 mg dinoprost) and
      eCG (300 IU) im at device withdrawal. Mean serum progesterone concentrations were
      greater for ewes treated with new versus reused devices (P < 0.05), but there
      were no significant effects on ovarian follicular development, namely: proportion
      of ewes that reached ovulation/treated ewes (8/10, 9/10, and 10/10); day of
      emergence of the ovulatory follicle (2.9 +/- 1.8, 1.8 +/- 2.4, and 2.5 +/- 1.1
      days after CIDR-G insertion); and lifespan of the ovulatory follicle (5.4 +/-
      1.8, 6.5 +/- 2.2, and 5.6 +/- 1.0 days) for devices of first, second, and third
      use, respectively. The proportion of ewes that ovulated from a new follicle
      emerging after CIDR-G insertion was 100% (10/10) with new devices, and 77.8%
      (7/9) and 80% (8/10) with devices used two and three times, respectively (P = not
      significant). In experiment 2, ewes (N = 319) received the short-term protocol as
      in experiment 1, using CIDR-G of first or third use (N = 158 and N = 161,
      respectively) for 6 days, with prostaglandin F(2alpha) and eCG given im at device
      withdrawal. Intrauterine (laparoscopy) fixed-time AI with fresh semen (100 *
      10(6) sperm) was done 52 to 57 hours after device withdrawal. Pregnancy rates
      were 80.4% (127/158) and 71.4% (115/161) for devices of first and third use,
      respectively (P = 0.06). We concluded that the CIDR-G with short-term protocol
      was effective for estrous synchronization and ovulation, with lower serum
      progesterone concentrations for reused devices. Three times used CIDR-G yielded a
      pregnancy rate >70%, which tended to be lower than that obtained with new
      devices, adding evidence of the detrimental effect of low serum progesterone
      concentrations on fertility in sheep.

PMID- 23127921
TI  - Mycoplasma infection in the uterus of early postpartum dairy cows and its
      relation to dystocia and endometritis.
AB  - This study investigated the incidence of mycoplasma infection in the uterus of
      postpartum Holstein dairy cows and its relationship to the occurrence of
      endometritis. The genital tracts of 209 cows from three dairy farms in the Iwate
      Prefecture, Japan, were examined at Weeks 5 and 7 postpartum. The condition of
      the cervicovaginal mucus was assessed using a Metricheck device and assigned a
      score from 0 (clear mucus) to 4 (purulent material with fetid odor). Intrauterine
      samples (N = 418) were collected at Weeks 5 and 7 postpartum using a cytobrush.
      After its withdrawal, swab samples were placed in mycoplasma culture broth at 37 
      degrees C for 72 hours. A novel and rapid polymerase chain reaction was used to
      detect seven mycoplasma species (Mycoplasma bovis, M. arginini, M.
      bovigenitalium, M. californicum, M. bovirhinis, M. alkalescens, and M.
      canadense). The cytobrush was also rolled gently along the length of a glass
      slide for subsequent polymorphonuclear neutrophil count. The diagnostic criteria
      for cytological endometritis were 6% or more and 4% or more polymorphonuclear
      neutrophils at Weeks 5 and 7, respectively. From a subset of cows, additional
      swabs were rolled against the cytobrush and then placed in transport medium.
      These samples were then plated on specific agar plates and cultured under aerobic
      and anaerobic conditions to identify other bacteria present. The incidence of
      dystocia at the last calving was compared in mycoplasma positive and negative
      cows. Of the seven mycoplasma species, only M. bovigenitalium was detected; it
      was detected in 31 of the 418 uterine swabs (7.4%). Twenty-four cows were
      positive for M. bovigenitalium (eight cows at Week 5, nine cows at Week 7, and
      seven cows at both Weeks 5 and 7). The incidence of dystocia was higher (P <
      0.0001) in mycoplasma positive (7/24; 29.2%) compared with mycoplasma negative
      (4/185; 2.2%) cows. However, there was no significant association between
      dystocia at last calving and subsequent uterine infection with other bacteria. In
      addition, the incidence of cytologic endometritis was higher (P < 0.05) in
      mycoplasma positive (8/16; 50%) than in mycoplasma negative (47/193; 24.4%) cows
      at Week 7. Therefore, we concluded that M. bovigenitalium infection in the uterus
      might be associated with recent dystocia and with cytologic endometritis in
      postpartum dairy cows.

PMID- 23127922
TI  - [Immunohistochemistry in the diagnosis of sarcomas].

PMID- 23127923
TI  - [Contribution of molecular biology for better management of soft tissue tumors].

PMID- 23127924
TI  - [Liposarcomas].

PMID- 23127925
TI  - [Changes in epithelioid soft tissue tumors].

PMID- 23127926
TI  - [New WHO classification of tumours of soft tissue and bone].

PMID- 23127927
TI  - [The revolution of the new generation sequencing].

PMID- 23127928
TI  - [Cervical cancer screening and the place of the HPV test in 2012].

PMID- 23127929
TI  - [Identity and intestinal pathologies: the Cdx2 homeotic gene].

PMID- 23127930
TI  - [Non-bioptic endoscopic diagnosis of dysplasia in the GI tract].

PMID- 23127931
TI  - [Transcription factors: which diagnostic applications?].

PMID- 23127932
TI  - [The E3N study: breast cancer and risk factors].

PMID- 23127933
TI  - [Molecular entities of the breast cancer: the difference is in the origin].

PMID- 23127934
TI  - [Young secretory carcinoma of the breast].

PMID- 23127935
TI  - [Micropapillary carcinoma of the breast: a full entity?].

PMID- 23127936
TI  - ["Molecular apocrine" carcinoma and disease of Cowden].

PMID- 23127937
TI  - [Personalized therapeutic targeting by exome analysis].

PMID- 23127938
TI  - [From karyotype to genome wide selection (GWS) sequencing in Burkitt lymphoma].

PMID- 23127939
TI  - [From foetopathology to disease-causing gene].

PMID- 23127940
TI  - [Introduction - Dysplasia of the gastrointestinal tract: definition,
      classification, what's new?].

PMID- 23127941
TI  - [" Non-intestinal " oesophageal and gastric dysplasia: terminology, diagnostic
      criteria].

PMID- 23127942
TI  - [Small intestinal dysplasia, an unknown dysplasia].

PMID- 23127943
TI  - [Serrated polyps and dysplasia: still poorly recognized lesions].

PMID- 23127944
TI  - [Digestive metaplasia: biology and physiopathology].

PMID- 23127945
TI  - [IgG4-related disease (IgG4-RD)].

PMID- 23127946
TI  - [Auto-immune pancreatitis: rational, diagnosis and differential diagnosis].

PMID- 23127947
TI  - [Head and neck IgG4 related disease].

PMID- 23127948
TI  - [IgG4-related systemic disease and renal involvement].

PMID- 23127949
TI  - [The ISO 15189 in pathology: 1515, 1789 or 14-18? Information and proposals to
      move forward without getting mad].

PMID- 23127950
TI  - [Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA).
      Background of the method and development of indications].

PMID- 23127951
TI  - [Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA).
      Experience of Tenon hospital (HU Est parisien, AP-HP Paris). The point of view of
      the pneumologist, the point of view of the cytologist].

PMID- 23127952
TI  - [Endoscopic ultrasound-guided transbronchial fine needle aspiration. The CHU of
      Lille's experience].

PMID- 23127953
TI  - [Specific aspects of immunocytochemistry].

PMID- 23127954
TI  - [ICC and IHC: techniques and quality assurance. Lessons from the French external
      quality assessment trials in IHC].

PMID- 23127955
TI  - [Diagnosis of sarcomas: the main traps].

PMID- 23127956
TI  - [Role of core needle biopsies in the diagnosis of sarcomas].

PMID- 23127957
TI  - The politics of health technology assessment in Poland.
AB  - OBJECTIVE: First, to identify risks associated with the scientific evaluation of
      drugs considered for state reimbursement in Poland through exploring strategies
      of influence employed by multinational drug companies in relation to the Agency
      for Health Technology Assessment (AHTAPol). Second, to ascertain whether the
      outcomes of drug evaluation meet the interests of the public payer in reimbursing
      cost-effective drugs supported by robust pharmacoeconomic evidence. METHODOLOGY:
      We conducted 109 in-depth semi-structured interviews with a purposive sample of
      stakeholders involved in the reimbursement process in Poland. We analysed four
      available documentary sources, including recommendations issued by the AHTAPol.
      RESULTS: AHTAPol recommendations were an instrumental part of the blame avoidance
      strategy by political elites. Drug producers utilised direct and indirect
      strategies of influence. The direct strategies involved building relationships
      with a circle of health technology assessment analysts and medical experts
      working for the Agency. The indirect strategies employed leaders of opinion in
      the medical milieu, patient organisations, and political elites to endorse policy
      positions favourable to drug companies. The AHTAPol positively recommended an
      increasing proportion of the drugs it assessed, many of them reported as not cost
      effective or supported by dubious pharmacoeconomic evidence. CONCLUSIONS: The
      strategies of influence entail a number of risks that may undermine the
      scientific evaluation of drugs. Some outcomes of drug evaluation may favour the
      interests of multinational drug companies over those of the public payer. We
      suggest that the risks involved in drug evaluation might be mitigated through (1)
      professionalization of health technology assessment; (2) restriction of job
      seeking and post public-payer employment; (3) disclosure and management of
      experts' conflicts of interest; (4) institutionalisation of patient and public
      involvement; and (5) increased institutional separation of the AHTAPol from
      political elites.

PMID- 23127958
TI  - Characterization of the mutant beta-subunit of beta-hexosaminidase for dimer
      formation responsible for the adult form of Sandhoff disease with the motor
      neuron disease phenotype.
AB  - The adult form of Sandhoff disease with the motor neuron disease phenotype is a
      rare neurodegenerative disorder caused by mutations in HEXB encoding the beta
      subunit of beta-hexosaminidase, yet the properties of mutant beta-subunits of the
      disease have not been fully determined. We identified a novel mutation (H235Y) in
      the beta-sheet of the (beta/alpha)8-barrel domain, in addition to the previously
      reported P417L mutation that causes aberrant splicing, in a Japanese patient with
      the motor neuron disease phenotype. Enzyme assays, gel filtration studies and
      immunoprecipitation studies with HEK293 cells transiently expressing mutant beta
      subunits demonstrated that the H235Y mutation abolished both alpha-beta and beta
      beta dimer formation without increasing beta-hexosaminidase activity, whereas
      other reported mutant beta-subunits (Y456S, P504S or R533H) associated with the
      motor neuron disease phenotype formed dimers. Structural analysis suggested that
      the H235Y mutation in the beta-sheet of the (beta/alpha)8-barrel domain changed
      the conformation of the beta-subunit by causing a clash with the E288 side chain.
      In summary, H235Y is the first mutation in the beta-sheet of the (beta/alpha)8
      barrel domain of the beta-subunit that abolishes alpha-beta and beta-beta dimer
      formation; the presented patient is the second patient to exhibit the motor
      neuron disease phenotype with P417L and a non-functional allele of HEXB.

PMID- 23127959
TI  - Osmotic shock-dependent redistribution of diacylglycerol kinase eta1 to non-ionic
      detergent-resistant membrane via pleckstrin homology and C1 domains.
AB  - Diacylglycerol kinase (DGK) participates in regulating the intracellular
      concentrations of two bioactive lipids, diacylglycerol and phosphatidic acid.
      DGKeta1 is a type II isozyme that contains a pleckstrin homology (PH) domain and
      a pair of C1 domains at the N-terminus and separated catalytic domains (catalytic
      subdomain-a and b). We previously reported that DGKeta1 expressed in COS-7 cells
      is translocated from the cytoplasm to punctate granules that partially include
      endosomes in response to stress stimuli such as osmotic shock. However, the
      biochemical properties of the stress-dependent behaviour of DGKeta1 remain
      unknown. Here, we have found that DGKeta1 is redistributed from the cytosol to
      the non-ionic detergent (Nonidet P-40)-resistant membrane (DRM) in response to
      osmotic shock. Our results strongly suggested that the Nonidet P-40 insolubility
      of DGKeta1 is due to neither cytoskeleton localization nor lipid raft
      association, implying that DGKeta1 is distributed to detergent-resistant membrane
      microdomains that have a low lipid-to-protein ratio. We revealed, using a series
      of DGKeta1 deletion mutants, that the PH and C1 domains play a pivotal role in
      osmotic shock-dependent DRM redistribution, whereas catalytic subdomain-a
      negatively regulates the event.

PMID- 23127960
TI  - Congenital myopathy with focal loss of cross-striations revisited.
AB  - In 1977 Wijngaarden et al. reported a Dutch family with a congenital myopathy
      characterized by external ophthalmoplegia and a remarkable histological feature,
      focal loss of cross-striations. A small number of other families with similar
      clinical and pathological features led to the consideration of this congenital
      myopathy as a distinct entity. Here we present more than 30years of follow-up
      from the Dutch family and report recently identified compound heterozygous
      mutations in the skeletal muscle ryanodine receptor (RYR1) gene, c.10627-2A>G and
      p.Arg3539His (c.10616G>A). Focal loss of cross-striations on muscle biopsy is
      another histopathological feature that should raise the possibility of RYR1
      involvement.

PMID- 23127961
TI  - Change in muscle strength over time in spinal muscular atrophy types II and III.
      A long-term follow-up study.
AB  - Whether muscle strength deteriorates with time in spinal muscular atrophy (SMA)
      types II and III is still debated. We present a long-term follow-up study on
      muscle strength in 30 patients with SMA types II and III. Median follow-up time
      was 17 years. Median number of assessments was four. All patients were assessed
      by Manual Muscle Testing (MMT), Brooke upper limb scale and EK scale. There was a
      difference in muscle strength of the upper limbs from first to last assessment in
      SMA II (p<0.0001) and SMA III patients (p<0.02). In SMA II patients, the rate of
      yearly decline in strength (% MRC score) was 0.22 units (p<0.03). The decline was
      independent of the grade of muscle strength at entry. In SMA II patients the
      decline in muscle strength was reflected in a loss upper limb function as
      measured by Brooke upper limb scale (p<0.0001) and motor function as measured by
      EK scale (p<0.0001), a loss of great importance to the patients' need for
      practical assistance. This study demonstrates loss of muscle strength over time
      in SMA II and III patients. Because of the very slow deterioration, it takes
      years to detect this change, which has to be taken into account in future
      treatment trials.

PMID- 23127962
TI  - Respiratory dysfunction in patients severely affected by GNE myopathy (distal
      myopathy with rimmed vacuoles).
AB  - GNE myopathy is a rare and mildly progressive autosomal recessive myopathy caused
      by GNE mutations. Respiratory dysfunction has not been reported in GNE myopathy
      patients. In this study, we retrospectively reviewed the respiratory function of
      39 severely affected GNE myopathy patients (13 men, 26 women) from medical
      records, and compared these parameters with various other patient characteristics
      (e.g., GNE mutations, age at onset, creatine kinase levels, and being wheelchair
      bound) for correlations. The mean % forced vital capacity [FVC] was 92 (26)
      (range, 16-128). In 12/39 (31%) patients, %FVC was <80%. Of these 12 patients, 11
      (92%) were entirely wheelchair-dependent. These patients exhibited significantly
      earlier onset (20 [4] vs. 30 [8] years, p<0.001) and lower creatine kinase levels
      (56 [71] vs. 279 [185] IU/L) than patients with normal respiratory function. Two
      patients exhibited severe respiratory failure and required non-invasive positive
      pressure ventilation. Patients with a homozygous mutation in the N
      acetylmannosamine kinase domain exhibited lower %FVC, while only one compound
      heterozygous patient with separate mutations in the uridinediphosphate-N
      acetylglucosamine 2-epimerase and the N-acetylmannosamine kinase domains had
      respiratory dysfunction. Our results collectively suggest that GNE myopathy can
      cause severe respiratory failure. Respiratory dysfunction should be carefully
      monitored in patients with advanced GNE myopathy characterized by early onset and
      homozygous homozygous mutations in the N-acetylmannosamine kinase domain.

PMID- 23127963
TI  - Enhanced anti-tumor effects of HPV16E7(49-57)-based vaccine by combined
      immunization with poly(I:C) and oxygen-regulated protein 150.
AB  - BACKGROUND: It is well known that both heat shock protein (HSP) and Toll-like
      receptor (TLR)3 agonist polyinosinic:polycytidylic acid (poly(I:C)) are capable
      of promoting the antigen-specific immune responses. In the current study, we
      assessed whether the anti-tumor effects of the HPV16E7(49-57)-based vaccine can
      be elevated by combined applications of poly(I:C) and oxygen-regulated protein
      150 (ORP150) in a mouse cervical cancer model. METHODS: Recombinant mouse ORP150
      and HPV E7(49-57) peptide were combined to passively form the ORP150-E7(49-57)
      complex under heat shock conditions. The effects of ORP150-E7(49-57) complex plus
      poly(I:C) adjuvant on lymphocyte proliferation and functional cytotoxic T cells
      were investigated by methyl thiazolyl tetrazolium (MTT), ELISPOT, and non
      radioactive cytotoxicity assays. Finally, the complex's therapeutic anti-tumor
      effects with and without adjuvant therapy were observed in a tumor challenge
      experiment. RESULTS: This combination vaccine approach significantly enhanced the
      proliferation of splenocytes and induced strong E7(49-57)-specific CTL responses.
      More importantly, the ORP150-E7(49-57) complex plus poly(I:C) vaccine format
      demonstrated more potent anti-tumor effects than ORP150-E7(49-57) complex alone
      or E7(49-57) plus poly(I:C) in TC-1 tumor-bearing mice. CONCLUSION: Both
      poly(I:C) and ORP150 chaperone can synergistically enhance the anti-tumor effects
      of the HPV16E7(49-57)-based vaccine in vitro and in vivo. This strategy provides
      a platform for the design of a tumor therapeutic vaccine capable of inducing an
      effective anti-tumor immune response.

PMID- 23127964
TI  - Saving the superstar: a review of the social factors affecting tiger conservation
      in India.
AB  - Tiger conservation in India represents an excellent case study of the many
      challenges facing conservation programs internationally. It is well understood
      that tigers are sensitive to human disturbances and large areas of habitat need
      to be protected for their conservation. Such protected areas in India are managed
      by the governments using an exclusionary approach. However, this approach is
      known to create several issues with local communities, including historical,
      legal, livelihood and management issues; with a volume of literature suggesting
      the inclusion of local communities in management. Yet, other evidence suggests
      that inclusion of communities in tiger conservation may lead to anthropogenic
      disturbances that can jeopardize tigers. The gravity of the situation is
      reflected in the recent disappearance of tigers from two key protected areas in
      India, the Sariska and Panna Tiger Reserves. This review paper connects the key
      literature from conservation biology, environmental history, management sciences,
      policy and political sciences to underline the gridlock of tiger conservation: it
      needs exclusive protected areas that antagonize communities, and it depends on
      the support of the same communities for success. We examine the possibility of
      reconciliation between these disciplines, and assert that research on tiger
      conservation needs to allow for an increasingly interdisciplinary approach. We
      call for a more integrated approach to tiger conservation, to examine the values
      inherent in conservation and to shed more light on the social factors that affect
      tiger conservation schemes.

PMID- 23127965
TI  - Institutional pressures, dynamic capabilities and environmental management
      systems: investigating the ISO 9000--environmental management system
      implementation linkage.
AB  - We hypothesize a model where domestic and international institutional pressures
      lead to the successful implementation of ISO 9000 and can in turn lead to the
      successful implementation of environmental management systems such as ISO 14001
      environmental certification systems or total quality environmental management
      (TQEM) systems. Using appropriate tests for mediation with dichotomous mediators
      and outcomes, we find that the model holds for a sample of 377 Chinese
      manufacturers in six major industrial groups in Suzhou, Dalian, and Tianjin. Our
      findings are consistent with the theory linking internal capabilities to
      heterogeneous external (in this case, institutional) pressures on organizations
      for environmentally proactive efforts. Our findings suggest that institutions in
      developing countries with significant environmental concerns such as China as
      well as foreign suppliers and partners to firms in these countries should
      encourage and support ISO 9000 implementations by local firms. These findings may
      influence other developing nations' adoption of quality and environmental process
      systems.

PMID- 23127966
TI  - A high-fat diet increases L-carnitine synthesis through a differential maturation
      of the Bbox1 mRNAs.
AB  - l-carnitine is a key molecule in both mitochondrial and peroxisomal lipid
      metabolisms. l-carnitine is biosynthesized from gamma-butyrobetaine by a reaction
      catalyzed by the gamma-butyrobetaine hydroxylase (Bbox1). The aim of this work
      was to identify molecular mechanisms involved in the regulation of l-carnitine
      biosynthesis and availability. Using 3' RACE, we identified four alternatively
      polyadenylated Bbox1 mRNAs in rat liver. We utilized a combination of in vitro
      experiments using hybrid constructs containing the Bbox1 3' UTR and in vivo
      experiments on rat liver mRNAs to reveal specificities in the different Bbox1
      mRNA isoforms, especially in terms of polyadenylation efficiency, mRNA stability
      and translation efficiency. This complex maturation process of the Bbox1 mRNAs in
      the liver was studied on rats fed a high-fat diet. High-fat diet selectively
      increased the level of three Bbox1 mRNA isoforms in rat liver and the alternative
      use of polyadenylation sites contributed to the global increase in Bbox1
      enzymatic activity and l-carnitine levels. Our results show that the maturation
      of Bbox1 mRNAs is nutritionally regulated in the liver through a selective
      polyadenylation process to adjust l-carnitine biosynthesis to the energy supply.

PMID- 23127967
TI  - Culturally sensitive mental health care: a study of contemporary psychiatric
      treatment for ultra-orthodox Jews in Israel.
AB  - BACKGROUND: The literature describes psychiatric treatment of ultra-orthodox Jews
      as complex and challenging, in light of this community's unique characteristics
      and the ideological gap between ultra-orthodox patients and secular
      professionals. Recent data indicate that patient-centred culturally sensitive
      care contributes to the treatment outcomes among cultural minorities. AIMS: To
      examine the effect of the level of a physician's religiosity and cultural
      sensitivity, as perceived by ultra-orthodox Jewish psychiatric patients, as well
      as the treatment venue (i.e. the distance of the treatment facility from the
      patients' community) on treatment outcomes (working alliance, medical adherence
      and the patients' social adaptation). METHODS: The sample included 38 ultra
      orthodox Jewish men and women receiving psychiatric treatment at the Lev Hasharon
      Mental Health Centre. The participants completed questionnaires about the
      physician's religiousness and cultural sensitivity, working alliance, medical
      adherence and social adaptation. RESULTS: Working alliance was positively related
      to the treatment location, meaning that patients were more committed and involved
      in the treatment when it took place in a facility distanced from their community.
      Working alliance was also correlated with medical adherence. Regression analysis
      revealed that the doctor's acquaintance with religion and cultural sensitivity
      predicted patients' reported social adaptation level. CONCLUSIONS: In contrary to
      common perceptions, ultra-orthodox patients are not necessarily reluctant to be
      treated by secular physicians. These patients prefer a discreet treatment far
      from their community's public eye. Their perception of a doctor who acknowledges
      and respects their religiosity positively affects the way that they perceive
      their social functioning. Culturally sensitive treatment enables patients to feel
      respected and acknowledged through their sociocultural affiliation, and not only
      through their disorder. It seems essential to train physicians about the
      importance of culturally sensitive treatment with this population.

PMID- 23127968
TI  - Deregulated microRNAs identified in isolated glioblastoma stem cells: an
      overview.
AB  - Glioblastoma multiforme (GBM), the most common and aggressive primary brain
      tumor, is extremely resistant to current treatment paradigms and has a high rate
      of tumor recurrence. Recent progress in the field of tumor-initiating cells
      suggests that GBM stem cells (GBMSCs) may be responsible for tumor progression,
      resistance to treatment, and tumor relapse. Therefore, understanding the
      biologically significant pathways involved in modulating GBMSC-specific
      characteristics offers great promise for development of novel therapeutics, which
      may improve therapeutic efficacy and overcome present drug resistance. In
      addition, targeting deregulated microRNA (miRNA) has arisen as a new therapeutic
      strategy in treating malignant gliomas. In GBMSCs, miRNAs regulate a wide variety
      of tumorigenic processes including cellular proliferation, stemness maintenance,
      migration/invasion, apoptosis, and tumorigenicity. Nevertheless, the latest
      progress with GBMSCs and subsequent miRNA profiling is limited by the
      identification and isolation of GBMSCs. In this review, we thus summarize current
      markers and known features for isolation as well as the aberrant miRNAs that have
      been identified in GBM and GBMSCs. 

PMID- 23127969
TI  - Epilepsy as progressive disorders: what is the evidence that can guide our
      clinical decisions and how can neuroimaging help?
AB  - There is evidence that some types of epilepsy progress over time, and an
      important part of this knowledge has derived from neuroimaging studies. Different
      authors have demonstrated structural damage more pronounced in individuals with a
      longer duration of epilepsy, and others have been able to quantify this
      progression over time. However, others have failed to demonstrate progression
      possibly due to the heterogeneity of individuals evaluated. Currently, temporal
      lobe epilepsy associated with hippocampal sclerosis is regarded as a progressive
      disorder. Conversely, for other types of epilepsy, the evidence is not so clear.
      The causes of this damage progression are also unknown although there is
      consistent evidence that seizure is one of the mechanisms. The conflicting data
      about epilepsy progression can be a challenge for clinical decisions for an
      individual patient. Studies with homogenous groups and longer follow-up are
      necessary for appropriate conclusions about the real burden of damage progression
      in epilepsies, and neuroimaging will be essential in this context.

PMID- 23127970
TI  - Ecological photodynamic therapy: new trend to disrupt the intricate networks
      within tumor ecosystem.
AB  - As with natural ecosystems, species within the tumor microenvironment are
      connected by pairwise interactions (e.g. mutualism, predation) leading to a
      strong interdependence of different populations on each other. In this review we
      have identified the ecological roles played by each non-neoplastic population
      (macrophages, endothelial cells, fibroblasts) and other abiotic components
      (oxygen, extracellular matrix) directly involved with neoplastic development. A
      way to alter an ecosystem is to affect other species within the environment that
      are supporting the growth and survival of the species of interest, here the tumor
      cells; thus, some features of ecological systems could be exploited for cancer
      therapy. We propose a well-known antitumor therapy called photodynamic therapy
      (PDT) as a novel modulator of ecological interactions. We refer to this as
      "ecological photodynamic therapy." The main goal of this new strategy is the
      improvement of therapeutic efficiency through the disruption of ecological
      networks with the aim of destroying the tumor ecosystem. It is therefore
      necessary to identify those interactions from which tumor cells get benefit and
      those by which it is impaired, and then design multitargeted combined
      photodynamic regimes in order to orchestrate non-neoplastic populations against
      their neoplastic counterpart. Thus, conceiving the tumor as an ecological system
      opens avenues for novel approaches on treatment strategies.

PMID- 23127971
TI  - Impact of tubal ligation on routes of dissemination and overall survival in
      uterine serous carcinoma.
AB  - OBJECTIVE: Abdominal peritoneal implants are characteristic of uterine serous
      carcinoma (USC). The presumed mechanism of dissemination is retrograde transit
      via the fallopian tube. We assessed the impact of tubal ligation (TL) on the
      metastatic profile and survival of USC patients. METHODS: Patient risk factors,
      process-of-care variables, and disease-specific parameters were annotated.
      Categorical variables were compared using the chi(2) test. Overall survival (OS)
      was estimated via the Kaplan-Meier method. RESULTS: Among 211 USC patients,
      fallopian tube status was documented in 142 patients; 35 had a history of TL and
      107 did not. When comparing patients with and without TL, positive peritoneal
      cytology was present, respectively, in 18.8% vs 45.0% (P=.01) and stage IV
      disease in 14.3% vs 34.6% (P=.02). Using Cox models, age was the sole significant
      determinant of OS in stage I/II USC. By contrast, age, lymphovascular space
      involvement, positive cytology, and TL independently and adversely affected
      survival in stage III/IV USC. Adjusting for these factors in a multivariable
      model, the association between TL and OS among patients with advanced disease
      yielded a hazard ratio of 8.61 (95% CI, 3.08-24.03; P<.001). The prevalence of
      lymphatic metastasis and nodal tumor burden was significantly greater in patients
      who underwent ligation. CONCLUSION: Patients with TL had significantly lower
      rates of positive cytology and stage IV disease than patients without TL. The
      lymphatic system appeared to be the dominant mode of spread after TL and was
      associated with a paradoxic worsening of OS, perhaps reflecting a delay in
      diagnosis.

PMID- 23127972
TI  - Body mass index, physical activity, and survival after endometrial cancer
      diagnosis: results from the Women's Health Initiative.
AB  - OBJECTIVE: While low physical activity and high body mass index (BMI) have been
      associated with higher endometrial cancer incidence, no previous studies have
      evaluated the association between physical activity and survival after
      endometrial cancer diagnosis, and studies on BMI and survival have not been
      performed in a prospective cohort. METHODS: We examined pre-diagnosis BMI and
      moderate- to vigorous-intensity physical activity in relation to overall and
      disease-specific survival among 983 postmenopausal women who were diagnosed with
      endometrial cancer in the Women's Health Initiative Observational Study and
      Clinical Trials. RESULTS: Over a median 5.2 (max 14.1) years from diagnosis to
      death or end of follow-up, 163 total deaths were observed, 66 of which were due
      to endometrial cancer. We observed a higher all-cause mortality hazard ratio (HR)
      = 1.85 (95% CI 1.19-2.88) comparing women with a BMI >= 35 kg/m(2) to women with
      BMI< 25 kg/m(2). For endometrial cancer-specific mortality the HR = 2.23 (95% CI
      1.09-4.54) comparing extreme BMI categories. To examine histologic subtypes we
      analyzed type I endometrial tumors separately and found an HR = 1.20 (95% CI 1.07
      1.35) associated with all-cause mortality for each 5-unit change in BMI. Moderate
      to vigorous-intensity physical activity was not associated with all-cause or
      endometrial cancer-specific mortality. CONCLUSIONS: Pre-diagnosis BMI, but not
      physical activity, was associated with survival among women with endometrial
      cancer. Future studies should investigate mechanisms and timing of BMI onset to
      better understand the burden of disease attributable to BMI.

PMID- 23127973
TI  - Frequent mutations in the RPL22 gene and its clinical and functional
      implications.
AB  - OBJECTIVE: To determine the frequency and spectrum of mutations in RPL22 a gene
      identified by The Cancer Genome Atlas (TCGA) as mutated in endometrioid
      endometrial cancer, and determine the relationship between RPL22 defects and
      clinicopathologic features. METHODS: Direct sequencing of the entire coding
      region of the RPL22 cDNA and exons 2/4 was performed in tumors with/without
      microsatellite instability (MSI). RPL22 expression was assessed by
      immunofluorescence microscopy in the KLE, RL952 and AN3CA cell lines, wildtype,
      heterozygous and homozygous mutants, respectively. Relationships between RPL22
      mutation and clinicopathological features were assessed using Chi-squared
      analysis and Student's t test. Progression-free survival (PFS) was calculated
      from the date of diagnosis to the date of recurrence. RESULTS: A single
      nucleotide deletion in an A8 coding repeat was identified in exon 2 of the RPL22
      gene in 116/226 (52%) of MSI-high tumors. No mutations were identified in MSI
      stable tumors. Only 2% of the tumors expressed a homozygous A deletion. RPL22
      mutation was not associated with stage, grade, race and lymphovascular space
      invasion. Women whose tumors harbored RPL22 mutations were significantly older
      (67 vs. 63years, p=0.005). There was no difference in PFS between patients with
      the wildtype and mutant genotypes. CONCLUSIONS: RPL22 is frequently mutated in
      MSI-high endometrioid endometrial cancers. The A8 mutation identified was not
      reported in the whole exome sequences analyzed by the TCGA. The demonstration of
      frequent mutation in RPL22 may point to a limitation of the exome capture and
      next generation sequencing analysis methods for some mononucleotide string
      mutations. Functional assessment of the RPL22 knockdown may be warranted.

PMID- 23127974
TI  - Nano-architectures of ordered hollow carbon spheres filled with carbon webs by
      template-free controllable synthesis.
AB  - Hollow carbon spheres with a carbon network structure inside have been
      synthesized in the absence of templates for the first time. The samples were
      characterized by scanning electron microscopy, transmission electron microscopy,
      x-ray diffraction, N(2) adsorption-desorption, and thermogravimetric analyses.
      The experimental results indicate that the core and the shell of this new
      structure contain both mesopores and micropores. Furthermore, the inner space and
      thickness of the hollow carbon spheres can be controlled by adjusting the molar
      ratio of the glucose and Na(2)SnO(3).H(2)O. Moreover, a possible formation
      mechanism has been suggested on the basis of time-dependent experiments. The
      electrocatalytic activity of methanol oxidation on Pt supported on HC
      electrocatalyst (Pt/HC@C) is 1.8 times higher than that of Pt supported on
      commercial Vulcan XC-72 carbon (Pt/C) electrocatalyst at the same Pt loadings.

PMID- 23127975
TI  - Risk prediction for adverse events after carotid artery stenting in higher
      surgical risk patients.
AB  - BACKGROUND AND PURPOSE: The goal of carotid artery stenting is to decrease the
      risk of stroke or other adverse events from carotid artery disease. Choosing a
      treatment strategy requires patient-specific information regarding periprocedural
      risk of adverse neurologic events. The aim of this study was to predict
      individual patient risk after carotid artery stenting in patients at higher risk
      for carotid endarterectomy. METHODS: Subjects enrolled in the Stenting and
      Angioplasty with Protection in Patients at High-Risk for Endarterectomy
      (SAPPHIRE) worldwide study underwent carotid artery stenting with distal
      protection. Only patients with at least 1 anatomic or comorbid factor associated
      with elevated surgical risk were included. Preprocedural factors were used to
      develop a model and integer-based risk score predicting stroke or death within 30
      days. The model was calibrated and internally validated using bootstrap
      resampling. RESULTS: Ten thousand one hundred eighty-six patients were included
      in the analysis. The overall rate of stroke or death was 3.6% at 30 days after
      carotid artery stenting. Independent predictors of adverse outcomes were
      increased age (P=0.006), history of stroke (P<0.001), history of transient
      ischemic attack presentation (P=0.001), recent (<4 weeks) myocardial infarction
      (P=0.006), dialysis treatment (P=0.007), need for cardiac surgery in addition to
      carotid revascularization (P=0.005), a right-sided carotid stenosis (P=0.006), a
      longer carotid plaque (P=0.012), the presence of a Type II or III aortic arch
      (P=0.035), and a tortuous carotid arterial system (P=0.004). The optimism
      adjusted C-statistic was 0.691. CONCLUSIONS: Commonly collected clinical and
      anatomic variables can identify patients at high and low risk for stroke or death
      after carotid artery stenting.

PMID- 23127976
TI  - Intravenous administration of human umbilical tissue-derived cells improves
      neurological function in aged rats after embolic stroke.
AB  - Intravenous administration of human umbilical tissue-derived cells (hUTC)
      improves neurological function in young adult rats after stroke. However, stroke
      is a major cause of death and disability in the aged population, with the
      majority of stroke patients 65 years and older. The present study investigated
      the effect of hUTC on aged rats after embolic stroke. Rats at the age of 18-20
      months were subjected to embolic middle cerebral artery (MCA) occlusion. Two
      groups of eight animals each were compared. The investigational group was
      injected intravenously with 1*10(7) cells/kg in serum-free culture medium
      (vehicle) 24 h after stroke onset, and the control group was treated with vehicle
      only at the same time poststroke. Intravenous administration of hUTC
      significantly improved neurological functional recovery without reducing infarct
      volume compared to vehicle-treated aged rats. Additionally, hUTC treatment
      significantly enhanced synaptogenesis and vessel density in the ischemic boundary
      zone (IBZ). Moreover, hUTC treatment resulted in a trend toward increased
      progenitor cell proliferation in the subventricular zone (SVZ) compared to
      vehicle-treated aged rats. Intravenous administration of hUTC improved functional
      recovery in aged rats after stroke. The enhancement of synaptogenesis and vessel
      density may contribute to the beneficial effects of hUTC in the treatment of
      stroke in the aged animal. 

PMID- 23127977
TI  - Black-white blood pressure disparities: depressive symptoms and differential
      vulnerability to blood lead.
AB  - BACKGROUND: Blacks have higher hypertension rates than whites, but the reasons
      for these disparities are unknown. Differential vulnerability, through which
      stress alters vulnerability to the effects of environmental hazards, is an
      emergent notion in environmental health that may contribute to these disparities.
      OBJECTIVES: We examined whether blacks and whites exhibit different associations
      between blood lead (BPb) and blood pressure (BP) and whether depressive symptoms
      may play a role. METHODS: Using the National Health and Nutrition Examination
      Survey 2005-2008, we regressed BP on the three-way interaction among
      race/ethnicity, BPb, and depressive symptoms in blacks and whites >= 20 years of
      age. RESULTS: Blacks but not whites showed a positive association between BPb and
      systolic blood pressure (SBP). The disparity in this association between blacks
      and whites appeared to be specific to the high depressive symptoms group. In the
      low depressive symptoms group, there was no significant black-white disparity
      (betainteraction = 0.9 mmHg; 95% CI: -0.9, 2.7). However, of those with high
      depressive symptoms, blacks and whites had 5.6 mmHg (95% CI: 2.0, 9.2) and 1.2
      mmHg (95% CI: -0.5, 2.9) increases in SBP, respectively, in association with each
      doubling of BPb (betainteraction = 4.4 mmHg; 95% CI: 0.5, 8.3). The pattern of
      results was similar for diastolic blood pressure. CONCLUSIONS: Our results
      suggest that depressive symptoms may contribute to the black-white disparity in
      the association between BPb and BP. Depressive symptoms may result, in part, from
      psychosocial stress. Our results support the notion that stress increases
      vulnerability to the health effects of environmental hazards and suggest that
      stress-related vulnerability may be an important determinant of racial/ethnic
      health disparities.

PMID- 23127978
TI  - Perivascular innate immune events modulate early murine vein graft adaptations.
AB  - OBJECTIVE: Innate immunity drives numerous cardiovascular pathologies. Vein
      bypass grafting procedures are frequently accompanied by low-grade wound
      contamination. We hypothesized that a peri-graft innate immune challenge, via an
      outside-in route, augments inflammatory responses, which subsequently drive a
      component of negative vein graft wall adaptations; moreover, adipose tissue
      mediates this immune response. METHODS: The inferior vena cava from a donor mouse
      was implanted into the common carotid artery of a recipient mouse utilizing a
      validated cuff technique (9-week-old male C57BL/6J mice). Slow-release low-dose
      (5 MUg) lipopolysaccharide (LPS) (n = 9) or vehicle (n = 9) was applied peri
      graft; morphologic analysis was completed (day 28). In parallel, vein-grafted
      mice received peri-graft LPS (n = 12), distant subcutaneous LPS (n = 6), or
      vehicle (n = 12), then day-1 and -3 harvest of grafts and adipose tissue for
      cytokines and toll-like receptor (TLR) signaling mRNA expression (qRT-PCR).
      RESULTS: All recipient mice survived, and all vein grafts were patent. Acute low
      dose local LPS challenge enhanced vein graft lumen loss (P = .04) and tended to
      augment intimal hyperplasia (P = .06). The surgical trauma of vein grafting
      universally upregulated key pro- and anti-inflammatory mediators within the day-1
      graft wall, but varied on TLR signaling gene expression. Local and distant LPS
      accentuated these patterns until at least postoperative day 3. LPS challenge
      enhanced the inflammatory response in adipose tissue (locally > distantly); local
      LPS upregulated adipose TLR-4 dramatically. CONCLUSIONS: Perivascular and distant
      inflammatory challenges potentiate the magnitude and duration of inflammatory
      responses in the early vein graft wall, negatively modulating wall adaptations,
      and thus, potentially contribute to vein graft failure. Furthermore, surgery
      activates innate immunity in adipose tissue, which is augmented (regionally >
      systemically) by LPS. Modulation of these local and distant inflammatory
      signaling networks stands as a potential strategy to enhance the durability of
      vascular interventions such as vein grafts.

PMID- 23127979
TI  - Cyclic adenosine monophosphate response-element binding protein activation by
      mitogen-activated protein kinase-activated protein kinase 3 and four-and-a-half
      LIM domains 5 plays a key role for vein graft intimal hyperplasia.
AB  - OBJECTIVE: Intimal hyperplasia (IH) is the main cause of vein graft stenosis or
      failure after bypass surgery. Basic investigations are proceeding in an animal
      model of mechanically desquamated arteries, and numerous molecules for potential
      IH treatments have been identified; however, neither insights into the mechanism
      of IH nor substantially effective treatments for its suppression have been
      developed. The goals of the present study are to use human vein graft samples to
      identify therapeutic target genes that control IH and to investigate the
      therapeutic efficacy of these candidate molecules in animal models. METHODS:
      Using microarray analysis of human vein graft samples, we identified two
      previously unrecognized IH-related genes, mitogen-activated protein kinase
      activated protein kinase 3 (MAPKAPK3) and four-and-a-half LIM domains 5 (FHL5).
      RESULTS: Transfer of either candidate gene resulted in significantly elevated
      vascular smooth muscle cell (VSMC) proliferation and migration. Interestingly,
      cotransfection of both genes increased VSMC proliferation in an additive manner.
      These genes activated cyclic adenosine monophosphate response-element (CRE)
      binding protein (CREB), but their mechanisms of activation were different.
      MAPKAPK3 phosphorylated CREB, but FHL5 bound directly to CREB. A CREB dominant
      negative protein, KCREB, which blocks its ability to bind CRE, repressed VSMC
      proliferation and migration. In a wire-injury mouse model, gene transfer of KCREB
      plasmid significantly repressed IH. In this vessel tissue, CRE-activated gene
      expression was repressed. Furthermore, we confirmed the changes in MAPKAPK3 and
      FHL5 expression using vein graft samples from eight patients. CONCLUSIONS: We
      successively identified two previously unrecognized IH activators, MAPKAPK3 and
      FHL5, using human vein graft samples. Gene transfer of KCREB repressed IH in an
      animal model. Inhibition of CREB function is a promising gene therapy strategy
      for IH.

PMID- 23127980
TI  - A modern experience with saccular aortic aneurysms.
AB  - OBJECTIVE: Repair of saccular aortic aneurysms (SAAs) is frequently recommended
      based on a perceived predisposition to rupture, despite little evidence that
      these aneurysms have a more malignant natural history than fusiform aortic
      aneurysms. METHODS: The radiology database at a single university hospital was
      searched for the computed tomographic (CT) diagnosis of SAA between 2003 and
      2011. Patient characteristics and clinical course, including the need for
      surgical intervention, were recorded. SAA evolution was assessed by follow-up CT,
      where available. Multivariate analysis was used to examine potential predictors
      of aneurysm growth rate. RESULTS: Three hundred twenty-two saccular aortic
      aneurysms were identified in 284 patients. There were 153 (53.7%) men and 131
      women with a mean age of 73.5+/-10.0 years. SAAs were located in the ascending
      aorta in two (0.6%) cases, the aortic arch in 23 (7.1%), the descending thoracic
      aorta in 219 (68.1%), and the abdominal aorta in 78 (24.2%). One hundred thirteen
      (39.8%) patients underwent surgical repair of SAA. Sixty-two patients (54.9%)
      underwent thoracic endovascular aortic repair, 22 underwent endovascular aneurysm
      repair (19.5%), and 29 (25.6%) required open surgery. The average maximum
      diameter of SAA was 5.0+/-1.6 cm. In repaired aneurysms, the mean diameter was
      5.4+/-1.4 cm; in unrepaired aneurysms, it was 4.4+/-1.1 cm (P<.001). Eleven
      patients (3.9%) had ruptured SAAs on initial scan. Of the initial 284 patients,
      50 patients (with 54 SAA) had CT follow-up after at least 3 months (23.2+/-19.0
      months). Fifteen patients (30.0%) ultimately underwent surgical intervention.
      Aneurysm growth rate was 2.8+/-2.9 mm/yr, and was only weakly related to initial
      aortic diameter (R2=.19 by linear regression, P=.09 by multivariate regression).
      Decreased calcium burden (P=.03) and increased patient age (P=.05) predicted
      increased aneurysm growth by multivariate analysis. CONCLUSIONS: While SAA were
      not found to have a higher growth rate than their fusiform counterparts, both
      clinical and radiologic follow-up is necessary, as a significant number
      ultimately require surgical intervention. Further clinical research is necessary
      to determine the optimal management of SAA.

PMID- 23127981
TI  - Fishbone penetration of the thoracic esophagus with prolonged asymptomatic
      impaction within the aorta.
AB  - A 54-year-old man with fishbone penetration of the thoracic esophagus and
      mediastinal hematoma was successfully managed with conservative treatment. Six
      month follow-up computed tomography (CT) revealed migration of the fishbone into
      the aorta; however, the patient was asymptomatic and refused surgery. Six years
      later, CT showed persistent impaction of the fishbone within the aorta, but the
      patient was healthy. To our knowledge, this is the first reported case of serial
      CT documentation of fishbone penetration of the esophagus with migration into and
      prolonged asymptomatic impaction within the aorta.

PMID- 23127982
TI  - Predicting the learning curve and failures of total percutaneous endovascular
      aortic aneurysm repair.
AB  - INTRODUCTION: Percutaneous endovascular aneurysm repair (PEVAR) has been shown to
      be feasible; however, technical success is variable, reported to be between 46.2%
      and 100%. The objective of this study was to quantify the learning curve of the
      PEVAR closure technique and identify predictors of closure failure. METHODS: We
      reviewed patient- and procedure-related characteristics in 99 consecutive
      patients who underwent PEVAR over a 30-month period in a single academic
      institution. A suture-mediated closure device (Proglide or Prostar XL) was used.
      Forward stepwise logistic regression was used to investigate associations between
      the failure of the closure technique and a number of patient and operative
      characteristics. To ensure objective assessment of the learning curve, a time
      dependent covariate measuring time in calendar quarters was introduced in the
      model. Poisson regression was used to model the trend of observed failure events
      of the percutaneous technique over time. RESULTS: Overall PEVAR technical success
      was 82%. Type of closure device (P<.35), patient's body mass index (P<.86), type
      of anesthesia (P<.95), femoral artery diameter (P<.09), femoral artery
      calcification (P<.56), and sheath size as measured in Fr (P<.17) did not
      correlate with closure failure rates. There was a strong trend for a decreasing
      number of failure events over time (P<.007). The average decrease in the odds of
      technical failure was 24% per calendar quarter. The predicted probability of
      closure failure decreased from 45% per patient at the time of the initiation of
      our PEVAR program to 5% per patient at the end of the 30-month period. There were
      two postoperative access-related complications that required surgical repair.
      Need for surgical cutdown in the event of closure failure prolonged the operative
      time by a mean of 45 minutes (P<.001). No groin infections were seen in the
      percutaneous group or the failed group. CONCLUSIONS: Technical failure can be
      reduced as the surgeon gains experience with the suture-mediated closure device
      utilized during PEVAR. Previous experience with the Proglide device does not seem
      to influence the learning curve.

PMID- 23127983
TI  - Intraluminal abdominal aortic aneurysm thrombus is associated with disruption of
      wall integrity.
AB  - OBJECTIVE: An association of intraluminal thrombus (ILT) with abdominal aortic
      aneurysm (AAA) growth has been suggested. Previous in vitro experiments have
      demonstrated that aneurysm-associated thrombus may secrete proteolytic enzymes
      and may develop local hypoxia that might lead to the formation of tissue-damaging
      reactive oxygen species. In this study, we assessed the hypothesis that ventral
      ILT thickness is associated with markers of proteolysis and with lipid oxidation
      in the underlying AAA vessel wall. METHODS: Ventral AAA tissue was collected from
      asymptomatic patients at the site of maximal diameter during open aneurysm
      repair. Segments were divided, one part for biochemical measurements and one for
      histologic analyses. We measured total cathepsin B, cathepsin S levels, and
      matrix metalloproteinase (MMP)-2 and MMP-9 activity. Myeloperoxidase and
      thiobarbituric acid reactive substances were determined as measures of lipid
      oxidation. Histologic segments were analyzed semiquantitatively for the presence
      of collagen, elastin, vascular smooth muscle cells (VSMCs), and inflammatory
      cells. Preoperative computed tomography angiography scans of 83 consecutive
      patients were analyzed. A three-dimensional reconstruction was obtained, and a
      center lumen line of the aorta was constructed. Ventral ILT thickness was
      measured in the anteroposterior direction at the level of maximal aneurysm
      diameter on the orthogonal slices. RESULTS: Ventral ILT thickness was positively
      correlated with aortic diameter (r=0.25; P=.02) and with MMP-2 levels (r=0.27;
      P=.02). No biochemical correlations were observed with MMP-9 activity or
      cathepsin B and S expression. No correlation between ventral ILT thickness and
      myeloperoxidase or thiobarbituric acid reactive substances was observed. Ventral
      ILT thickness was negatively correlated with VSMCs (no staining, 18.5
      [interquartile range, 12.0-25.5] mm; minor, 17.6 [10.7-22.1] mm; moderate, 14.5
      [4.6-21.7] mm; and heavy, 8.0 [0.0-12.3] mm, respectively; P=.01) and the amount
      of elastin (no staining, 18.6 [12.2-30.0] mm; minor, 16.5 [9.0-22.1] mm;
      moderate, 11.7 [2.5-15.3] mm; and heavy 7.7 [0.0-7.7] mm, respectively; P=.01) in
      the medial aortic layer. CONCLUSIONS: ILT thickness appeared to be associated
      with VSMCs apoptosis and elastin degradation and was positively associated with
      MMP-2 concentrations in the underlying wall. This suggests that ILT thickness
      affects AAA wall stability and might contribute to AAA growth and rupture. ILT
      thickness was not correlated with markers of lipid oxidation.

PMID- 23127984
TI  - Supraclavicular decompression for neurogenic thoracic outlet syndrome in
      adolescent and adult populations.
AB  - OBJECTIVE: This study was conducted to better define clinical results and
      understand factors determining responsiveness to surgical treatment for
      neurogenic thoracic outlet syndrome (NTOS) in adolescent and adult populations.
      METHODS: A retrospective review was conducted for 189 patients with disabling
      NTOS who underwent primary supraclavicular decompression (scalenectomy, brachial
      plexus neurolysis and first rib resection, with or without pectoralis minor
      tenotomy) from April 2008 to December 2010. Clinical characteristics were
      compared between 35 adolescent patients (aged<21 years) and 154 adults (aged>21
      years). Functional outcome measures were assessed before surgery and at 3- and 6
      month follow-up using a composite NTOS Index combining the Disabilities of the
      Arm, Shoulder and Hand (DASH) survey, the Cervical-Brachial Symptom Questionnaire
      (CBSQ), and a 10-point visual analog scale (VAS) for pain. RESULTS: Adolescent
      and adult patients were not significantly different with respect to sex (overall
      72.5% female), side affected (58.7% right, 60.3% dominant limb), bony anomalies
      (23.3%), previous injury (55.6%), coexisting pain disorders (11.1%), and positive
      responses to scalene muscle anesthetic blocks (95.6%). Compared with adults,
      adolescent patients had a significantly (P<.05) lower incidence of depression
      (11.4% vs 41.6%), motor vehicle injury (5.7% vs 20.1%), previous operations
      (11.4% vs 29.9%), preoperative use of opiate medications (17.1% vs 44.8%), and
      symptom duration>2 years (24.2% vs 50.0%). Mean preoperative NTOS Index (scale 0
      100) was significantly lower in adolescent vs adult patients (46.5+/-3.6 vs
      58.5+/-1.7; P=.009), and hospital length of stay was 4.4+/-0.2 vs 4.9+/-0.1 days
      (P=.03), but the rate of postoperative complications was no different (overall,
      4.2%). Although both groups exhibited significant improvement in functional
      outcome measures at 3 and 6 months, adolescent patients had significantly lower
      NTOS Index (10.4+/-3.1 vs 39.3+/-3.3; P<.001) and use of opiate medications
      (11.4% vs 47.4%; P<.001) compared with adults. CONCLUSIONS: Adolescents
      undergoing supraclavicular decompression for NTOS had more favorable preoperative
      characteristics and enhanced 3-month and 6-month functional outcomes than adults.
      Further study is needed to delineate the age-dependent and independent factors
      that promote optimal surgical outcomes for NTOS.

PMID- 23127985
TI  - Surgical techniques and early experience of endovascular treatment of complex
      thoracic aortic disease via minithoracotomy.

PMID- 23127986
TI  - Decline in gait performance detected by an electronic walkway system in 907 older
      adults of the population-based KORA-Age study.
AB  - BACKGROUND: Gait changes at older ages are a strong predictor of a decline in
      lower extremity functions. However, large population-based studies assessing gait
      parameters in various gait tasks are lacking. OBJECTIVE: We investigated the
      relationship of age, the use of mobility aids and being fitted with an
      endoprosthesis with selected gait parameters, assessed in different walking
      tasks. METHODS: In the population-based KORA-Age study, data from 907 men and
      women aged 65-91 years were obtained using the validated electronic walkway
      system GAITRite, which quantifies spatiotemporal gait parameters in the
      measurement range of a 488 * 61 cm walkway mat. Participants completed three
      walking tasks at different speeds (normal, slow and fast) and a fourth walking
      task at normal speed with the additional task of counting backwards (dual-task
      walking). Additionally, the impact of endoprostheses (hip or knee) and mobility
      aids was assessed. RESULTS: The highest relative age-related decline for velocity
      was observed during dual-task walking (26.1% for men and 23.4% for women) and for
      step length during fast walking (20.2 and 14.4%) when comparing participants aged
      <70 years with those aged >=85 years. Weaker performances for velocity, cadence
      and step length were observed among women with knee or hip endoprostheses (fast
      walking speed) (p < 0.05). Across all walking tasks, significant differences
      between mobility aid users and nonusers were observed for velocity and step
      length among both men and women (p < 0.05). CONCLUSION: A decline in gait
      performance is most notable in fast speed and dual-task walking, in age-related
      endoprosthesis and mobility aid analyses. The marked relative decrease in gait
      parameters in these difficult gait tasks may be attributed to lacking resources
      for compensation among the elderly.

PMID- 23127987
TI  - Rationally designed cyclic analogues of luteinizing hormone-releasing hormone:
      enhanced enzymatic stability and biological properties.
AB  - This article describes the rational design, synthesis and pharmacological
      properties of amide-linked cyclic analogues of Luteinizing Hormone-Releasing
      Hormone (LHRH) with substitutions at positions 1 (Pro), 6 (D-Leu/D-Trp), 9 (Aze)
      and 10 (BABA/Acp). These LHRH analogues fulfil the conformational requirements
      that are known in the literature (bend in the 5-8 segment) to be essential for
      receptor recognition and activation. Although, they are characterised by an
      overall low binding affinity to the LHRH-I receptor, the cyclic analogues that
      were studied and especially the cyclo(1-10)[Pro(1), D-Leu(6), BABA(10)] LHRH,
      exhibit a profoundly enhanced in vitro and in vivo stability and improved
      pharmacokinetics in comparison with their linear counterpart and leuprolide. Upon
      receptor binding, cyclo(1-10)[Pro(1), D-Leu(6), BABA(10)] LHRH causes
      testosterone release in C57/B16 mice (in vivo efficacy) that is comparable to
      that of leuprolide. Testosterone release is an acutely dose dependent effect that
      is blocked by the LHRH-I receptor antagonist, cetrorelix. The pharmacokinetic
      advantages and efficacy of cyclo(1-10)[Pro(1), D-Leu(6), BABA(10)] LHRH render
      this analogue a promising platform for future rational drug design studies
      towards the development of non-peptide LHRH mimetics.

PMID- 23127988
TI  - Adenosiland: walking through adenosine receptors landscape.
AB  - Adenosine receptors (ARs) belong to the family of G protein-coupled receptors.
      Four distinct subtypes are known, termed adenosine A(1), A(2A), A(2B) and A(3).
      receptors and they are regulated by adenosine which is one of the most ancient
      and widespread chemical messengers in the animal and plant kingdoms. Moreover,
      ARs are widely distributed in human body and they are expressed with different
      density in diverse tissues. It is not surprising that they are involved in the
      regulation of several physiopathological processes. Adenosiland represents the
      first tentative of an integrated bioinformatics and chemoinformatics web-resource
      dedicated to adenosine receptors. This informatics platform provides a wide
      ranging of structure based and ligand based query functions to facilitate the
      exploration of adenosine receptor structures from primary sequences to three
      dimensional architectures. Here, we present an overview of Adenosiland platform
      describing the most valuable searching tools and their functionalities.
      Adenosiland can be freely accessed at http://mms.dsfarm.unipd.it/Adenosiland/.

PMID- 23127989
TI  - Discovery of new scaffolds for rational design of HCV NS5B polymerase inhibitors.
AB  - Hepatitis C virus (HCV) NS5B polymerase is a key target for the development of
      anti-HCV drugs. Here we report on the identification of novel allosteric
      inhibitors of HCV NS5B through a combination of structure-based virtual screening
      and in vitro NS5B inhibition assays. One hundred and sixty thousand compounds
      from the Otava database were virtually screened against the thiazolone inhibitor
      binding site on NS5B (thumb pocket-2, TP-2), resulting in a sequential down
      sizing of the library by 2.7 orders of magnitude to yield 59 NS5B non-nucleoside
      inhibitor (NNI) candidates. In vitro evaluation of the NS5B inhibitory activity
      of the 59 selected compounds resulted in a 14% hit rate, yielding 8 novel
      structural scaffolds. Of these, compound 1 bearing a 4-hydrazinoquinazoline
      scaffold was the most active (IC(50) = 16.0 MUM). The binding site of all 8 NNIs
      was mapped to TP-2 of NS5B as inferred by a decrease in their inhibition potency
      against the M423T NS5B mutant, employed as a screen for TP-2 site binders. At 100
      MUM concentration, none of the eight compounds exhibited any cytotoxicity, and
      all except compound 8 exhibited between 40 and 60% inhibition of intracellular
      NS5B polymerase activity in BHK-NS5B-FRLuc reporter cells. These inhibitor
      scaffolds will form the basis for future optimization and development of more
      potent NS5B inhibitors.

PMID- 23127990
TI  - Heparin-polynitroxides: synthesis and preliminary evaluation as cardiovascular
      EPR/MR imaging probes and extracellular space-targeted antioxidants.
AB  - We report here the synthesis of heparin-polynitroxide derivatives (HPNs) in which
      nitroxide moieties are linked either to uronic acid or glycosamine residues of
      the heparin macromolecule. HPNs have low anticoagulant activity, possess
      superoxide scavenging properties, bind to the vascular endothelium/extra-cellular
      matrix and can be detected by EPR and MRI techniques. As the vascular wall
      targeted redox-active paramagnetic compounds, HPNs may have both diagnostic
      (molecular MRI) and therapeutic (ecSOD mimics) applications.

PMID- 23127991
TI  - Diagnostic accuracy of premanipulative vertebrobasilar insufficiency tests: a
      systematic review.
AB  - STUDY DESIGN: A systematic review of diagnostic accuracy studies. OBJECTIVE: To
      evaluate the diagnostic accuracy of the premanipulative vertebrobasilar
      insufficiency (VBI) tests. SUMMARY OF BACKGROUND DATA: The aim of premanipulative
      vertebrobasilar testing is to evaluate the adequacy of blood supply to the brain,
      by compressing the vertebral artery and examining for the onset of signs and
      symptoms of cerebrovascular ischemia. Although clinicians consider pre
      manipulative testing important before applying spinal manipulations, the
      diagnostic accuracy has not been systematically reviewed. METHODS: A search was
      made in PUBMED, CINAHL and EMBASE databases from their date of inception until
      2nd May 2012. Studies were included if they compared a VBI test with a reference
      test, and sensitivity and specificity were reported or could be calculated. The
      methodological quality of the studies was evaluated using QUADAS. Agreement
      between reviewers was calculated and expressed as a percentage and quantified by
      kappa statistics. RESULTS: Of the 1677 potential citations only 4 studies were
      included, all of questionable quality. Sensitivity was low and ranged from 0 to
      57%, specificity from 67 to 100%, positive predictive value from 0% to 100%, and
      negative predictive value from 26 to 96%. The positive likelihood ratio ranged
      from 0.22 to 83.25 and the negative likelihood ratio from 0.44 to 1.40.
      CONCLUSION: Based on this systematic review of only 4 studies it was not possible
      to draw firm conclusions about the diagnostic accuracy of premanipulative tests.
      However, data on diagnostic accuracy indicate that the premanipulative tests do
      not seem valid in the premanipulative screening procedure. A surplus value for
      premanipulative tests seems unlikely.

PMID- 23127992
TI  - The application of Mechanical Diagnosis and Therapy and changes on MRI findings
      in a patient with cervical radiculopathy.
AB  - Cervical radiculopathy is an unusual presentation for patients with neck pain.
      Its diagnosis and management is uncertain. This case report presents an example
      of a patient with cervical radiculopathy who responded to Mechanical Diagnosis
      and Therapy, and whose MRI findings changed over time. 

PMID- 23127993
TI  - Patients' priorities regarding outpatient physiotherapy care: a qualitative and
      quantitative study.
AB  - BACKGROUND: Little knowledge is available on the attributes pertaining to
      physiotherapy care that patients consider most important. OBJECTIVES: To
      establish patients' priorities with regard to outpatient physiotherapy care and
      to determine the association between gender, age, level of education, perceived
      health, frequency of visiting a physiotherapist (PT), and patients' priorities.
      DESIGN, PARTICIPANTS AND METHODS: 8 Focus group discussions that were conducted
      with 53 patients were used to generate aspects of care that were considered
      important for patients. Subsequently, a self-administered questionnaire,
      consisting of the aspects of care that were revealed in the focus group
      discussions, was handed out to 20 consecutively visiting patients by 22 PTs who
      were working in an outpatient private practice. The patients were asked to rate
      the importance of each aspect. RESULTS: The focus group discussions generated 48
      aspects of care that were included in the questionnaire; 358 (81%) patients
      returned the questionnaire. All the proposed aspects were perceived as being
      important. The most important aspect was that "the PT is expert in his
      professional field." Patients who were older, received a lower level of
      education, were less healthy, and attended more frequently, indicated more
      aspects as important; however, the different subgroups ranked the priorities, to
      a large extent, in the same manner. DISCUSSION AND CONCLUSION: The findings of
      the survey can be used to make PTs more responsive to the expectations of
      patients, to educate patients about the role of physiotherapy care, and to
      develop instruments for measuring patients' experience and satisfaction with
      physiotherapy care.

PMID- 23127994
TI  - Effects of the pelvic rotatory control method on abdominal muscle activity and
      the pelvic rotation during active straight leg raising.
AB  - The aim of this study was to examine the effects of the pelvic rotatory control
      method on abdominal muscle activity and the amount of pelvic rotation while
      maintaining active straight leg raising (ASLR) at the level of the target bar. In
      this study, 27 healthy female volunteers were instructed to perform ASLR, ASLR
      with a pelvic compression belt, and ASLR with the pelvic rotatory control method.
      Surface electromyography (EMG) data were collected from the bilateral rectus
      abdominis (RA), external oblique abdominis (EO), and internal oblique abdominis
      (IO) muscles, and angles of pelvic rotation were measured using a 3-dimensional
      motion-analysis system. EMG activity of all abdominal muscles was greater and
      pelvic rotation was less in the pelvic rotatory control method compared with both
      the conventional ASLR method and the ASLR with pelvic compression belt method (p
      < 0.05). The findings suggest that ASLR with the pelvic rotatory control method
      is effective in activating the abdominal muscles and minimizing unwanted
      lumbopelvic rotation during ASLR exercise.

PMID- 23127995
TI  - In vitro evaluation of elastin-like polypeptide-collagen composite scaffold for
      bone tissue engineering.
AB  - OBJECTIVES: Collagen and elastin are two key structural proteins found in the
      extra-cellular matrices (ECMs) of most tissues, yet very little is known about
      the response of bone cells to elastin or its derivatives. Recently, we have
      designed and characterized a novel class of ECM-based composite scaffolds with
      collagen and a genetically engineered polymer, elastin-like polypeptide (ELP) and
      subsequently showed their superior mechanical properties and drug release
      characteristics compared to collagen scaffolds. The objective of this research
      was to evaluate osteoblast growth and expression on these composite scaffolds.
      METHODS: A thorough biochemical and morphological characterization was performed
      on MC3T3-E1 pre-osteoblast cells cultured on collagen and ELP-collagen scaffolds.
      Cell viability was assessed using a live/dead assay. Total DNA content of all
      cells present on various surfaces was quantified. Pre-osteoblast differentiation
      was assessed by measuring the alkaline phosphatase and osteocalcin production.
      Mineral deposition by the cultured cells was visualized using the Von Kossa
      stain. RESULTS: Our results showed that the ELP-collagen scaffolds were suitable
      substrates for cell culture that allowed MC3T3-E1 pre-osteoblast cell attachment,
      differentiation, and subsequent mineralization over a period of 3 weeks. The ELP
      collagen scaffolds displayed equivalent biocompatibility and cell-interacting
      properties to those of the neat collagen scaffolds. SIGNIFICANCE: The novel ELP
      collagen composite material may have future implications as a scaffold material
      for bone tissue engineering applications, for example, the treatment of alveolar
      bone loss.

PMID- 23127997
TI  - Preface to the fifth edition. AAOMS Parameters of Care 2012.

PMID- 23127998
TI  - Surgical correction of maxillofacial skeletal deformities.

PMID- 23127996
TI  - Adar is essential for optimal presynaptic function.
AB  - RNA editing is a powerful way to recode genetic information. Because it
      potentially affects RNA targets that are predominantly present in neurons, it is
      widely hypothesized to affect neuronal structure and physiology. Across phyla,
      loss of the enzyme responsible for RNA editing, Adar, leads to behavioral
      changes, impaired locomotion, neurodegeneration and death. However, the
      consequences of a loss of Adar activity on neuronal structure and function have
      not been studied in detail. In particular, the role of RNA editing on synaptic
      development and physiology has not been investigated. Here we test the
      physiological and morphological consequences of the lack of Adar activity on the
      Drosophila neuromuscular junction (NMJ). Our detailed examination of synaptic
      transmission showed that loss of Adar increases quantal size, reduces the number
      of quanta of neurotransmitter released and perturbs the calcium dependence of
      synaptic release. In addition, we find that staining for several synaptic vesicle
      proteins is abnormally intense at Adar deficient synapses. Consistent with this
      finding, Adar mutants showed a major alteration in synaptic ultrastructure.
      Finally, we present evidence of compensatory changes in muscle membrane
      properties in response to the changes in presynaptic activity within the Adar
      mutant NMJs.

PMID- 23127999
TI  - Patient assessment.

PMID- 23128000
TI  - Cleft and craniofacial surgery.

PMID- 23128001
TI  - Trauma surgery.

PMID- 23128002
TI  - Temporomandibular joint surgery.

PMID- 23128003
TI  - Diagnosis and management of pathological conditions.

PMID- 23128004
TI  - Reconstructive surgery.

PMID- 23128005
TI  - Anesthesia in outpatient facilities.

PMID- 23128006
TI  - Cosmetic maxillofacial surgery.

PMID- 23128007
TI  - Dentoalveolar surgery.

PMID- 23128008
TI  - Dental and craniomaxillofacial implant surgery.

PMID- 23128009
TI  - Epigenetics and crop improvement.
AB  - There is considerable excitement about the potential for epigenetic information
      to contribute to heritable variation in many species. Our understanding of the
      molecular mechanisms of epigenetic inheritance is rapidly growing, and it is now
      possible to profile the epigenome at high resolution. Epigenetic information
      plays a role in developmental gene regulation, response to the environment, and
      in natural variation of gene expression levels. Because of these central roles,
      there is the potential for epigenetics to play a role in crop improvement
      strategies including the selection for favorable epigenetic states, creation of
      novel epialleles, and regulation of transgene expression. In this review we
      consider the potential, and the limitations, of epigenetic variation in crop
      improvement.

PMID- 23128010
TI  - miRNA regulatory variation in human evolution.
AB  - Recent advancements have revealed a complex post-transcriptional regulatory
      network in humans involving miRNAs. However, the contribution of miRNAs to human
      evolution, especially interindividual variation associated with miRNAs, is only
      beginning to be studied. In this article, we illustrate the extent of variation
      in miRNA-mediated post-transcriptional regulation in humans. Based on evidence
      from recent studies, we argue that the evolution of post-transcriptional control
      may be adaptive, and that it not only complements the primary transcriptional
      regulation by transcription factors (TFs), but also diversifies gene expression
      phenotypes, thereby generating genetic novelty on which natural selection
      subsequently acts. Given that current evolutionary analyses and genotype
      phenotype mapping are primarily focused on protein-coding genes and TF-mediated
      regulations, comprehensive examination of post-transcriptional variations should
      be included in future studies to add a new dimension to understanding of human
      phenotypic evolution.

PMID- 23128011
TI  - The development of group acupuncture for chronic knee pain was all about
      providing frequent electroacupuncture.

PMID- 23128012
TI  - Transcranial Doppler ultrasonography with jugular vein compression can detect
      impairment of intracranial compliance.

PMID- 23128013
TI  - Pure gait disturbance displayed by malingerers: case report of two patients.

PMID- 23128014
TI  - Anticoagulation therapy a risk factor for the development of chronic subdural
      hematoma.
AB  - OBJECTIVE: Chronic subdural hematoma (CSDH) is a common disease among the elderly
      and with increasing incidence we have chosen to focus on associations between
      development and recurrence of CSDH and anticoagulation and/or antiplatelet agent
      therapy. METHODS: We conducted a retrospective review of 239 patients undergoing
      surgery for CSDH over a period of six years (2006-2011). Risk factors such as
      age, head trauma, anticoagulant and/or antiplatelet agent therapy and co
      morbidity were investigated along with gender, coagulation status, laterality,
      surgical method and recurrence. RESULTS: Seventy-two percent of the patients were
      male and the mean age was 71.8 years (range 28-97 years). Previous fall with head
      trauma was reported in 60% of the patients while 16% were certain of no previous
      head trauma. The majority of patients (63%) in the non-trauma group were
      receiving anticoagulants and/or antiplatelet agent therapy prior to CSDH
      presentation, compared to 42% in the trauma group. Twenty-four percent
      experienced recurrence of the CSDH. There was no association between recurrence
      and anticoagulant and/or antiplatelet agent therapy. CONCLUSION: Anticoagulant
      and/or antiplatelet aggregation agent therapy is more prevalent among non
      traumatic CSDH patients but does not seem to influence the rate of CSDH
      recurrence.

PMID- 23128015
TI  - Fatal aneurysmal subarachnoid haemorrhage: causes of 30-day in-hospital case
      fatalities in a large single-centre historical patient cohort.
AB  - BACKGROUND: Mortality rates of up to 40% in the early phase following an
      aneurysmal subarachnoid haemorrhage (SAH) indicate that the overall case-fatality
      rate is predominantly influenced by the initial phase of the disease. This
      analysis investigates the in-hospital causes of death (CODs) within 30 days of
      admission in patients suffering from a SAH. METHODS: Of the 591 consecutive
      patients with SAHs from ruptured cerebral aneurysms, 85 patients who died within
      30 days after admission were analysed. The various CODs were classified as
      cerebral or non-cerebral events. A Kaplan-Meier survival analysis was performed
      for the cerebral and non-cerebral CODs to identify the specific chronology of
      occurrence. RESULTS: The median cumulative fatality was 4 days. A cerebral oedema
      as a result of initial brain damage after ictus was the predominant COD (n=24,
      28.2%; median cumulative fatality, 1 day; IQR, 1-4 days; SEM, 0.680), followed by
      cerebral infarction caused by delayed cerebral ischaemia (DCI) (n=13, 15.3%;
      median cumulative fatality, 9 days; IQR, 4-13 days; SEM, 1.379). Renal failure
      was the predominant non-cerebral COD before cardiac and pulmonary complications
      (n=6, 7.1%). CONCLUSIONS: Mortalities after SAHs predominantly occur within the
      first days after ictus. The dominant cerebral cause of death is early initial
      cerebral oedema, followed by DCI.

PMID- 23128016
TI  - Usage of eltrombopag for chronic immune thrombocytopenia as a pretreatment for
      splenectomy.

PMID- 23128017
TI  - Independent multicenter study of Riata and Riata ST implantable cardioverter
      defibrillator leads.
AB  - BACKGROUND: Riata and Riata ST leads (St Jude Medical, Sylmar, CA) are prone to
      failure. There are no independent multicenter reports regarding Riata or Riata ST
      lead performance. OBJECTIVE: To conduct a retrospective multicenter study of
      Riata and Riata ST leads that were implanted and followed at 7 centers. METHODS:
      The study included adults who received St Jude Medical Riata or Riata ST leads.
      Data for Quattro Secure leads were obtained from an earlier study. RESULTS: From
      2002 to 2010, 1081 patients received a Riata (n = 774) or Riata ST (n = 307)
      lead. Follow-up was longer for Riata than Riata ST leads (4.2 +/- 2.4 years vs
      3.3 +/- 1.7 years; P<.0001). During the study, 67 leads failed (6.2%), including
      62 of 774 Riata (8.0%) and 5 of 307 Riata ST (1.6%) leads. Forty-seven of 67 lead
      failures (70.1%) were caused by electrical malfunction, and 20 lead failures
      (29.9%) were due to externalized conductors (ECs) that were electrically intact.
      Of 110 leads examined fluoroscopically, ECs were found in 26 of 81 Riata (32%)
      and 1 of 29 Riata ST (3.4%) leads. Of 26 Riata leads with ECs, 7 (27%) were
      malfunctioning. Riata leads had lower overall and malfunction free survival
      compared to Quattro leads (P<.0001), while Riata ST lead survival was not
      different (P = .422). CONCLUSIONS: The survival of Riata (but not Riata ST) leads
      was lower than Quattro leads; however, Riata ST leads had significantly shorter
      follow-up than Riata leads. ECs were common in Riata leads, and more than a
      quarter of Riata leads that had ECs were malfunctioning. Our observations suggest
      that systematic fluoroscopic examination of patients with Riata leads is
      appropriate.

PMID- 23128018
TI  - Electrophysiological effects of acute atrial stretch on persistent atrial
      fibrillation in patients undergoing open heart surgery.
AB  - BACKGROUND: The electrophysiologic effects of acute atrial dilatation and
      dedilatation in humans with chronic atrial fibrillation remains to be elucidated.
      OBJECTIVE: To study the electrophysiological effects of acute atrial dedilatation
      and subsequent dilatation in patients with long-standing persistent atrial
      fibrillation (AF) with structural heart disease undergoing elective cardiac
      surgery. METHODS: Nine patients were studied. Mean age was 71 +/- 10 years, and
      left ventricular ejection was 46% +/- 6%. Patients had at least moderate mitral
      valve regurgitation and dilated atria. After sternotomy and during extracorporal
      circulation, mapping was performed on the beating heart with 2 multielectrode
      arrays (60 electrodes each, interelectrode distance 1.5 mm) positioned on the
      lateral wall of the right atrium (RA) and left atrium (LA). Atrial pressure and
      size were altered by modifying extracorporal circulation. AF electrograms were
      recorded at baseline after dedilation and after dilatation of the atria
      afterward. RESULTS: At baseline, the median AF cycle length (mAFCL) was 184 +/-
      27 ms in the RA and 180 +/- 17 ms in the LA. After dedilatation, the mAFCL
      shortened significantly to 168 +/- 13 ms in the RA and to 168 +/- 20 ms in the
      LA. Dilatation lengthened mAFCL significantly to 189 +/- 17 ms in the RA and to
      185 +/- 23 ms in the LA. Conduction block (CB) at baseline was 14.3% +/- 3.6% in
      the RA and 17.3% +/- 5.5% in the LA. CB decreased significantly with dedilatation
      to 7.4% +/- 2.9% in the RA and to 7.9% +/- 6.3% in the LA. CB increased
      significantly with dilatation afterward to 15.0% +/- 8.3% in the RA and to 18.5%
      +/- 16.0% in the LA. CONCLUSIONS: Acute dedilatation of the atria in patients
      with long-standing persistent AF causes a decrease in the mAFCL in both atria.
      Subsequent dilatation increased the mAFCL. The amount of CB decreased with
      dedilatation and increased with dilatation afterward in both atria.

PMID- 23128019
TI  - Efforts to enhance catheter stability improve atrial fibrillation ablation
      outcome.
AB  - BACKGROUND: Contemporary techniques to enhance anatomical detail and catheter
      contact during atrial fibrillation (AF) ablation include (1) the integration of
      preacquired tomographic reconstructions with electroanatomical mapping (3
      dimensional image integration [I-EAM]), (2) the use of steerable introducers
      (SIs), and (3) high-frequency jet ventilation (HFJV). OBJECTIVE: To prove that
      using these stabilizing techniques during AF ablation improves 1-year procedural
      outcome. METHODS: We studied 300 patients undergoing AF ablation at our
      institution. Patients were divided into 3 equal treatment groups (100 patients
      each) on the basis of the tools utilized: (1) group 1: AF ablation performed
      without I-EAM, SI, or HFJV; (2) group 2: AF ablation performed using I-EAM and
      SI, but without HFJV; and (3) group 3: AF ablation performed with I-EAM, SI, and
      HFJV. The primary outcome was freedom from AF 1 year after a single ablation
      procedure. The burden of both acute and chronic pulmonary vein reconnection was
      also assessed. RESULTS: Patients from groups 2 and 3 had significantly more
      nonparoxysmal AF (17% vs 30% vs 39%; P = .002), larger left atria (4.2 +/- 0.8 cm
      vs 4.4 +/- 0.7 cm vs 4.5 +/- 0.8 cm; P<.001), and higher body mass index (BMI;
      28.5 +/- 5.8 kg/m2 vs 29.1 +/- 4.8 kg/m2 vs 31.2 +/- 5.4 kg/m2; P<.001). Despite
      these differences, with adoption of I-EAM, SI, and HFJV we noted a significant
      improvement in 1-year freedom from AF (52% vs 66% vs 74%; P = .006) as well as
      fewer acute (1.1 +/- 1.2 vs 0.9 +/- 1.1 vs 0.6 +/- 0.9; P = .03) and chronic (3.5
      +/- 0.9 vs 3.2 +/- 0.9 vs 2.4 +/- 1.0; P = .02) pulmonary vein reconnections.
      CONCLUSIONS: The incorporation of contemporary tools to enhance anatomical detail
      and ablation catheter stability significantly improved 1-year freedom from AF
      after ablation.

PMID- 23128020
TI  - Current status of Amblyomma ovale (Acari: Ixodidae) in Panama.
AB  - The genus Amblyomma is the most diverse and relevant among the Neotropical ticks.
      In Panama, this genus contains 19 species, including Amblyomma ovale. There is a
      lack of knowledge of the ecology of A. ovale in Panama, and thus the aim of this
      work is to report on its geographical distribution and its spectrum of vertebrate
      hosts. We reviewed data of ticks collected in different areas of Panama from 2007
      to 2012 and found parasitism of A. ovale in 625 vertebrates, corresponding to 21
      species (2 species of birds and 19 mammal species). A. ovale is present in
      different environments of Panama, from lowlands to places with 800m altitude,
      including rural towns, disturbed forests, and wilderness areas.

PMID- 23128021
TI  - Effect of phosphamidon on cognition and oxidative stress and its modulation by
      ascorbic acid and 4'-chlorodiazepam in rats.
AB  - Neurosteroids and micronutrient are known to possess neuromodulator and
      neuroprotective activities. The present study was designed to investigate the
      effect of 4'-chlorodiazepam (4CD) or ascorbic acid (Vit C) on phosphamidon (PM)
      induced modulation of cognitive function and oxidative stress in male Wistar
      rats. Cognitive function was measured by using step-down latency (SDL) on a
      continuous avoidance apparatus and transfer latency (TL) on an elevated plus
      maze. Oxidative stress was estimated by measuring brain malondialdehyde (MDA)
      level, protein carbonyl (PC) and reduced glutathione (GSH) activity. A
      significant reduction in both acquisition and retention in SDL was found for the
      PM treated group at weeks 6 and 8 as compared to the control (p<0.001). PM caused
      a significant prolongation in both acquisition and retention in TL at 6 and 8
      weeks as compared to the control (p<0.001). Two-week treatment of 4CD or Vit C
      antagonized the effect of PM on SDL and TL at 8th week. PM produced a
      statistically significant increase in the brain MDA and PC levels (p<0.001) and a
      significant decrease in the brain GSH activity (p<0.001). Treatment with 4CD or
      Vit C attenuated the effect of PM on MDA, PC and GSH activities. Results of this
      study suggest that Vit C and 4CD have potential in reversing cognitive
      dysfunction and oxidative stress induced by toxicants like PM in the brain.

PMID- 23128022
TI  - Effects of adolescent onset voluntary drinking followed by ethanol vapor exposure
      on subsequent ethanol consumption during protracted withdrawal in adult Wistar
      rats.
AB  - Epidemiological studies have demonstrated that heavy drinking and alcohol abuse
      and dependence peak during the transition between late adolescence and early
      adulthood. The objective of the present study was to determine whether a model of
      early onset adolescent ethanol drinking exposure that is followed by an ethanol
      vapor regimen during late adolescence and young adulthood leads to an increase in
      drinking in adulthood. In this model, initiation of voluntary ethanol drinking in
      adolescence, using a sweetened solution, was followed by an 8-wk intermittent
      ethanol vapor regimen in Wistar rats. A limited-access two-bottle choice paradigm
      was then used to measure intake of a 10% (w/v) ethanol solution. No differences
      in water intake (g/kg), total fluid intake (ml/kg) and body weight (g) were
      observed between air-exposed and ethanol-vapor exposed groups during the pre
      vapor and post-vapor phases. The 8 weeks of ethanol vapor exposure was found to
      produce only a modest, but statistically significant, elevation of ethanol intake
      during the protracted withdrawal period, compared to air-exposed rats. A
      significant increase in ethanol preference ratio was also observed in ethanol
      vapor exposed rats during the sucrose-fading phase, but not during the protracted
      withdrawal period. The findings from the present study suggest that in addition
      to alcohol exposure, environmental variables that impact appetitive as well as
      consumptive behaviors may be important in developing robust drinking effects that
      model, in animals, the increased risk for alcohol dependence seen in some human
      adolescents who begin drinking at an early age.

PMID- 23128023
TI  - Perspective: Optimal protein intake in the elderly.

PMID- 23128024
TI  - Core functions of nursing home social services departments in the United States.
AB  - OBJECTIVE: To report social services departmental involvement in 52 functions.
      DESIGN: Cross-sectional data collected from a nationally representative sample of
      1071 nursing home social services directors who were asked to report the extent
      to which their department was involved in 52 functions (activities). The
      functions were organized under the framework of the NASW Clinical Indicators for
      Social Work and Psychosocial Services in Nursing Homes. SETTING: Nursing home.
      PARTICIPANTS: Social services directors. INTERVENTION: Not applicable.
      MEASUREMENT: Self-administered survey. RESULTS: Eighty percent of respondents
      indicated their department is "usually or always" involved in a core set of 24
      functions (out of 52). For each of the 52 functions, at least 40% of departments
      are at least sometimes involved. CONCLUSION: Findings reveal both a core set of
      functions in which departments are "usually or always" involved, as well as many
      in which some, but not all, departments are involved. This variability of
      departmental involvement suggests that staff should clearly communicate the
      functions of their department so that residents, families, fellow staff, and the
      community know what can be expected. Future research should investigate how to
      maximize social services to achieve and maintain the highest possible quality of
      life for residents, address family concerns, and contribute to team
      effectiveness.

PMID- 23128025
TI  - Perspective: Exercise and protein supplementation in frail elders.

PMID- 23128026
TI  - Carrot or stick? Improving the discharge process.

PMID- 23128027
TI  - Facile preparation of luminescent and intelligent gold nanodots based on
      supramolecular self-assembly.
AB  - A new strategy for preparing luminescent and intelligent gold nanodots based on
      supramolecular self-assembly is described in this paper. The supramolecular self
      assembly was initiated through electrostatic interactions and ion pairing between
      palmitic acid and hyperbranched poly(ethylenimine). The resulting structures not
      only have the dynamic reversible properties of supramolecules but also possess
      torispherical and highly branched architectures. Thus they can be regarded as a
      new kind of ideal nanoreactor for preparing intelligent Au nanodots. By preparing
      Au nanodots within this kind of supramolecular self-assembly, the environmental
      sensitivity of intelligent polymers and the optical, electrical properties of Au
      nanodots can be combined, endowing the Au nanodots with intelligence. In this
      paper, a supramolecular self-assembly process based on dendritic
      poly(ethylenimine) and palmitic acid was designed and then applied to prepare
      fluorescent and size-controlled Au nanodots. The pH response of Au nanodots
      embodied by phase transfer from oil phase to water phase was also investigated.

PMID- 23128029
TI  - Laser in situ keratomileusis using optimized aspheric profiles and cyclotorsion
      control to treat compound myopic astigmatism with high cylinder.
AB  - PURPOSE: To evaluate the visual outcomes after laser in situ keratomileusis
      (LASIK) surgery to correct primary compound myopic astigmatism with high cylinder
      performed using a fast-repetition-rate excimer laser platform with optimized
      aspheric profiles and cyclotorsion control. SETTING: Vissum Corporation and
      Division of Ophthalmology, Universidad Miguel Hernandez, Alicante, Spain. DESIGN:
      Retrospective consecutive observational nonrandomized noncomparative case series.
      METHODS: Eyes with primary compound myopic astigmatism and a cylinder power over
      3.00 diopters (D) had uneventful LASIK with femtosecond flap creation and fast
      repetition-rate excimer laser ablation with aspheric profiles and cyclotorsion
      control. Visual, refractive, and aberrometric outcomes were evaluated at the 6
      month follow-up. The astigmatic correction was evaluated using the Alpins method
      and Assort software. RESULTS: The study enrolled 37 eyes (29 patients; age range
      19 to 55 years). The significant reduction in refractive sphere and cylinder 3
      months and 6 months postoperatively (P<.01) was associated with improved
      uncorrected distance visual acuity (P<.01). Eighty-seven percent of eyes had a
      spherical equivalent within +/-0.50 D; 7.5% of eyes were retreated. There was no
      significant induction of higher-order aberrations (HOAs). The targeted and
      surgically induced astigmatism magnitudes were 3.23 D and 2.96 D, respectively,
      and the correction index was 0.91. The safety and efficacy indices were 1.05 and
      0.95, respectively. CONCLUSIONS: Laser in situ keratomileusis for primary
      compound myopic astigmatism with high cylinder (>3.00 D) performed using a fast
      repetition-rate excimer laser with optimized aspheric profiles and cyclotorsion
      control was safe, effective, and predictable and did not cause significant
      induction of HOAs.

PMID- 23128030
TI  - Smoothness assessment of corneal stromal surfaces.
AB  - PURPOSE: To assess the accuracy of the scanning electron microscopy (SEM) and
      present alternative approaches to quantify surface roughness based on numerical
      analysis. SETTING: Department of Ophthalmology, Maisonneuve-Rosemont Hospital,
      University of Montreal, Montreal, Quebec, Canada. DESIGN: Experimental study.
      METHODS: Lamellar stromal cuts were performed on human corneas using a
      femtosecond laser or a microkeratome. The photodisrupted stromal surfaces were
      processed for SEM, and images were acquired at *1000 magnification. First, images
      were evaluated by independent observers. Second, images were analyzed based on
      first-order and second-order statistics of gray-level intensities. Third, 3
      dimensional (3-D) surface reconstructions were generated from pairs of SEM images
      acquired at 2 angles. RESULTS: Results show that traditional assessment of
      roughness based on evaluating SEM images by independent observers can be replaced
      by computer-image texture analysis; an algorithm was developed to avoid
      subjective and time-consuming observations. The 3-D reconstructions allowed
      additional characterization of surface properties that was not possible with SEM
      images alone. Significant fluctuations in surface height were lost, although they
      could be retrieved using 3-D reconstructions. CONCLUSIONS: Image texture analysis
      allowed objective and repeatable assessment of stromal surface roughness;
      however, full assessments of surface-height fluctuations required 3-D
      reconstruction. These complementary methodologies offer a more comprehensive
      assessment of corneal surface roughness in clinical applications.

PMID- 23128028
TI  - Independent contributions of alcohol and stress axis hormones to painful
      peripheral neuropathy.
AB  - Painful small-fiber peripheral neuropathy is a debilitating complication of
      chronic alcohol abuse. Evidence from previous studies suggests that
      neuroendocrine mechanisms, in combination with other, as yet unidentified actions
      of alcohol, are required to produce this neuropathic pain syndrome. In addition
      to neurotoxic effects of alcohol, in the setting of alcohol abuse neuroendocrine
      stress axes release glucocorticoids and catecholamines. Since receptors for these
      stress hormones are located on nociceptors, at which they can act to cause
      neuronal dysfunction, we tested the hypothesis that alcohol and stress hormones
      act on the nociceptor, independently, to produce neuropathic pain. We used a rat
      model, which allows the distinction of the effects of alcohol from those produced
      by neuroendocrine stress axis mediators. We now demonstrate that topical
      application of alcohol and exposure to unpredictable sound stress, each alone,
      has no effect on the nociceptive threshold. However, when animals that had
      previous exposure to alcohol were subsequently exposed to stress, they rapidly
      developed mechanical hyperalgesia. Conversely, sound stress followed by topical
      alcohol exposure also produced mechanical hyperalgesia. The contribution of
      stress hormones was prevented by spinal intrathecal administration of
      oligodeoxynucleotides antisense to beta(2)-adrenergic or glucocorticoid receptor
      mRNA, which attenuates receptor level in nociceptors, as well as by adrenal
      medullectomy. These experiments establish an independent role of alcohol and
      stress hormones on the primary afferent nociceptor in the induction of painful
      peripheral neuropathy.

PMID- 23128031
TI  - Short-term effects of the 2008 cold spell on mortality in three subtropical
      cities in Guangdong Province, China.
AB  - BACKGROUND: Few studies have been conducted to investigate the impact of extreme
      cold events on mortality in subtropical regions. OBJECTIVE: In the present study
      we aimed to investigate the effects of the 2008 cold spell on mortality and the
      possibility of mortality displacement in three subtropical cities in China.
      METHODS: Daily mortality, air pollution, and weather data were collected from
      2006 to 2009 in Guangzhou, Nanxiong (no air pollutants), and Taishan. We used a
      polynomial distributed lag model (DLM) to analyze the relationship between the
      2008 cold spell and mortality. To observe the mortality displacement of the cold
      spell, we estimated the cumulative effects at lag0, lag0-6, lag0-13, lag0-20, and
      lag0-27 separately. RESULTS: During the 2008 cold spell, the cumulative risk of
      nonaccidental mortality increased significantly in Guangzhou [relative risk (RR)
      = 1.60; 95% CI: 1.19, 2.14] and Taishan (RR = 1.60; 95% CI: 1.06, 2.40) when
      lagged up to 4 weeks after the cold spell ended. Estimated effects at lag0-27
      were more pronounced for males than for females, for respiratory mortality than
      for cardiovascular mortality, and for the elderly (>= 75 years of age) than for
      those 0-64 years of age. Most of the cumulative RRs increased with longer lag
      times in Guangzhou and Taishan. However, in Nanxiong, the trend with cumulative
      RRs was less consistent, and we observed no statistically significant
      associations at lag0-27. CONCLUSION: We found associations between the 2008 cold
      spell and increased mortality in the three subtropical cities of China. The lag
      effect structure of the cold spell varied with location and the type of
      mortality, and evidence of short-term mortality displacement was inconsistent.
      These findings suggest that extreme cold is an important public health problem in
      subtropical regions.

PMID- 23128032
TI  - Decompression of inflammatory edema along with endothelial cell therapy expedites
      regeneration after renal ischemia-reperfusion injury.
AB  - Increased pressure due to postischemic edema aggravates renal ischemia
      reperfusion injury (IRI). Prophylactic surgical decompression using
      microcapsulotomy improves kidney dysfunction after IRI. Supportive cell therapy
      in combination with microcapsulotomy might act synergistically protecting kidney
      function against IRI. The effects of therapeutic endothelial cell application
      alone and in combination with microcapsulotomy were investigated in a xenogenic
      murine model of 45-min warm renal ischemia. Renal function and perfusion were
      determined before as well as 2 and 18 days postischemia by (99m)Tc-MAG3 imaging
      and laser Doppler. Histological analysis included H&E stains and immunohistology
      for endothelial marker MECA-32, cell proliferation marker Ki-67, and macrophage
      marker F4/80. Histomorphological changes were quantified using a tubular injury
      score. Ischemia of 45 min led to severe tissue damage and a significant decrease
      in renal function and perfusion. Microcapsulotomy and cell therapy alone had no
      significant effect on renal function, while only surgical decompression
      significantly increased blood flow in ischemic kidneys. However, the combination
      of both microcapsulotomy and cell therapy significantly improved kidney function
      and perfusion. Combination therapy significantly reduced morphological injury of
      ischemic kidneys as determined by a tubular injury score and MECA-32 staining.
      Macrophage infiltration evidenced by F4/80 staining was significantly reduced.
      The Ki-67 proliferation index was increased, suggesting a regenerative
      environment. While microcapsulotomy and cell therapy alone have limited effect on
      renal recovery after IRI, combination therapy showed synergistic improvement of
      renal function, perfusion, and structural damage. Microcapsulotomy may create a
      permissive environment for cell therapy to work. 

PMID- 23128033
TI  - Subablative Er:YAG laser effect on enamel demineralization.
AB  - OBJECTIVES: To characterize the cariostatic potential of a low-energy Er:YAG
      laser treatment. METHODS: Twelve sound premolars were selected. Two 2 * 1 mm
      windows were created on each tooth and randomly assigned to L(1) and L(2) groups.
      Three sites in each window were chosen with the middle site as the control and
      the left and right ones receiving Er:YAG laser treatment of 5.1 J/cm(2) (L(1)) or
      2.0 J/cm(2) (L(2)), respectively. The teeth were further subjected to 4-day pH
      cycling to create caries-like lesions. After mineral quantification using a micro
      computed tomography scanner, the preventive effects (DeltaML = mineral loss of
      the control area minus that of the lased area) of L(1) and L(2) treatments were
      calculated based on the difference in the gray value of the control and lased
      sites. RESULTS: Significant inhibitory effects of L(1) and L(2) on enamel
      demineralization were demonstrated (both p <= 0.001), with the L(1) treatment
      having a greater effect (45.2%) than the L(2) treatment (25.2%, p = 0.004).
      CONCLUSIONS: Subablative low-energy Er:YAG laser irradiation can significantly
      prevent enamel demineralization potentially through the retardation of enamel
      diffusion. This study confirmed that high-energy laser treatment, which may
      damage the peripheral and underlying tissues, may not be needed for caries
      prevention.

PMID- 23128034
TI  - Inclusion of latent tuberculosis infection as a separate entity into the
      international classification of diseases.
AB  - The 11th revision of the International Classification of Diseases (ICD-11)
      proposed by the WHO is currently in the consultation phase. In common with
      previous versions of the ICD this revised version does not contain a code for
      latent tuberculosis infection (LTBI), contrasting with the inclusion of a large
      number of codes for various manifestations of active tuberculosis (TB). Inclusion
      of a separate code for LTBI into ICD-11 is critically important for
      epidemiological, clinical and research purposes. On behalf of the Paediatric
      Tuberculosis Network European Trials group, we encourage colleagues worldwide who
      are caring for TB patients or are involved in TB research to join us in
      supporting the case for a long overdue ICD code for LTBI.

PMID- 23128036
TI  - Attachment in old age: theoretical assumptions, empirical findings and
      implications for clinical practice.
AB  - Contemporary theoretical models that conceptualize attachment as a biologically
      based behavioral system that is activated under threat offer a heuristic
      theoretical framework to understand processes involved in aging and particularly
      individual differences in coping with the inevitable losses associated with aging
      and age-related disease, including dementia. This paper provides a systematic
      qualitative review of research concerning attachment in old age published between
      1983 and June 2012. Four major findings emerged. First, studies suggest age
      related changes with regard to the number and type of attachment figures, with
      older adults, compared to younger adults, having less attachment relations.
      Moreover, so-called symbolic attachments (e.g., to God or a deceased loved one)
      become more prominent in old age. Second, the quality of attachment changes with
      increasing age, with significant decreases in attachment anxiety, but not in
      attachment avoidance. Third, late-life attachment is in theoretically predicted
      ways associated with indices of intraindividual and interindividual functioning.
      Finally, insecure attachment has a negative impact on subjective caregiver burden
      and behavior of patients with dementia. There is some evidence suggesting that
      attachment-based interventions show positive effects in treating problem
      behaviors associated with dementia. However, these conclusions need to be
      interpreted within the context of important methodological limitations, stressing
      the need for future research in this domain. Guidelines for future research are
      outlined.

PMID- 23128035
TI  - A multi-sample confirmatory factor analysis of PTSD symptoms: what exactly is
      wrong with the DSM-IV structure?
AB  - Within the DSM-IV, PTSD symptoms are rationally classified as assessing one of
      three symptom domains: reexperiencing, avoidance/numbing, or hyperarousal.
      However, two alternative four-factor models have been advocated as superior to
      the DSM-IV framework, based on confirmatory factor analysis. In the Numbing
      model, symptoms of emotional numbing are differentiated from avoidance. In the
      Dysphoria model, several symptoms of numbing and hyperarousal are combined to
      form a factor purported to assess general psychological distress. Examination of
      these models, within 29 separate data sets, supports two conclusions. First,
      contrary to its conceptual underpinnings, the Dysphoria model differs empirically
      from the Numbing model solely in the correlation predicted between two
      hyperarousal symptoms; all other predicted correlations made by the two models
      are substantively identical. Second, when the factor analytic presumption of
      simple structure is relaxed to allow for potential presentation order effects,
      other plausible symptom structures emerge. In particular, the fit of the DSM-IV
      model improved dramatically and was a better fit to the data than either four
      factor model. The ostensible inferiority of the DSM-IV model may be due to a
      methodological artifact stemming from the order in which symptoms are typically
      assessed. The provisional decision to revise the structure of PTSD symptoms in
      the DSM-5 in light of confirmatory factor analytic results may be misguided.

PMID- 23128037
TI  - Abdominal wall incision with or without exteriorization of bowel: results from a
      fetal lamb model for the embryogenesis of gastroschisis.
AB  - INTRODUCTION: The embryogenesis of gastroschisis is not completely understood.
      The aim of our study was to evaluate the impact of a simple abdominal wall defect
      versus a defect including eviscerated intestine or omentum for the development of
      gastroschisis in a fetal lamb model. MATERIAL AND METHODS: At mid-gestation (day
      77) an abdominal wall defect was fetoscopically created with three different
      approaches in 19 German blackhead sheep. The intestine was eviscerated in 7
      fetuses (group 1). The peritoneum was incised and a patch of the omentum pulled
      through the incision in 5 fetuses (group 2). In 7 fetuses (group 3) the skin and
      rectus muscle were incised until the peritoneum was visible. In this group, no
      abdominal contents were exteriorized and the peritoneum was left intact. A second
      fetoscopic procedure was performed 21 days later, assessing the condition and
      extension of eviscerated bowel. The fetus was retrieved by Cesarean section on
      day 132 and evaluated. RESULTS: The second fetoscopy acting as a control for the
      creation of gastroschisis demonstrated eviscerated and inflamed intestine in all
      3 groups. The amount of eviscerated intestine did not appear to depend on the
      size of the defect nor on its duration. DISCUSSION: It appears that a simple
      incision of the abdominal wall with intact peritoneum is sufficient for the
      development of gastroschisis in a fetal sheep model. This finding may improve the
      understanding of the etiology of gastroschisis.

PMID- 23128038
TI  - Can cortical silent period and motor threshold be practical parameters in the
      comparison of patients with generalized epilepsy and patients with psychogenic
      non-epileptic seizures?.
AB  - BACKGROUND/AIM: This study aimed to compare the cortical excitability of patients
      with generalized tonic-clonic seizures (GTCSs) and that of patients with
      psychogenic non-epileptic seizures (PNESs). METHODS: Patients were classified
      into groups according to their electroencephalogram (EEG) findings and seizure
      types: group 1 = GTCS with an abnormal EEG, group 2 = GTCS with a normal EEG and
      group 3 = PNES with a normal EEG. The control group included healthy volunteers
      with normal EEGs. Cortical silent period (CSP) and motor threshold (MT) were
      measured for all groups and the results were compared. RESULTS: CSPs were
      significantly prolonged in groups 1 and 2 when compared with group 3 and the
      control group. No differences were found between the MT measurements of all
      groups. CONCLUSION: The prolongation of CSP may demonstrate the differences
      between the pathophysiological mechanisms of GTCS and those of PNES.

PMID- 23128039
TI  - Physical properties and in vitro evaluation of collagen-chitosan-calcium
      phosphate microparticle-based scaffolds for bone tissue regeneration.
AB  - Due to limitations of bone autografts and allografts, synthetic bone grafts using
      osteoconductive biomaterials have been designed. In this study, collagen-chitosan
      calcium phosphate microparticle-based scaffolds fused with glycolic acid were
      compared to their counterparts without collagen in terms of degradation,
      cytocompatibility, porosity, and Young's modulus. It was found that 26-30%
      collagen was incorporated and that hydroxyapatite was present. Moreover, there
      were no differences between control and collagen scaffolds in degradation,
      cytocompatibility, porosity, and Young's modulus. In general, scaffolds exhibited
      23% porosity, 0.6-1.2 MPa Young's modulus, 23% degradation over 4 weeks, and
      supported a four to seven fold increase in osteoblast cell number over 7 days in
      culture. Collagen can be incorporated into these bone graft substitute scaffolds,
      which show an improved degradation profile.

PMID- 23128041
TI  - Alemtuzumab for multiple sclerosis: who and when to treat?

PMID- 23128042
TI  - Control of charge transfer in donor/acceptor metal-organic frameworks.
AB  - Charge transfer (CT) of D(0)A(0) <-> D(delta+)A(delta-) not only involves an
      electron transfer from D to A, but also generates a new spin set of S = 1/2 spins
      with an exchange interaction. Therefore, the control of CT in multidimensional
      frameworks could be an efficient way to design electronically/magnetically
      functional materials. The use of redox-active metal complexes as D and/or A
      building blocks expands the variety of such D/A frameworks with the formulation
      of D(m)A(n) (m, n >= 1), permitting the design of donor/acceptor metal-organic
      frameworks (D/A-MOFs). This Account summarizes our ongoing research on the design
      of D/A-MOFs and on the systematic control of CT in such D/A-MOFs toward the
      discovery of unique electronic/magnetic materials exhibiting nontrivial
      phenomena. For this purpose, the D/A combinations of carboxylate-bridged
      paddlewheel-type diruthenium(II,II) complexes ([Ru(2)(II,II)]) that act as one
      electron (1e(-)) donors and polycyanoorganic acceptors such as 7,7,8,8-tetracyano
      p-quinodimethane (TCNQ) and N,N'-dicyanoquinodiimine (DCNQI) have been chosen. 
      Even in the covalently bonded motif, the CT in this system is systematically
      dependent on the intrinsic ionization potential (I(D)) and electron affinity
      (E(A)) of the D and A units, respectively, which is controllable by chemical
      modification of the D/A units. As we consider the energy difference between the
      HOMO of D and the LUMO of A (DeltaE(H-L)(DA)) instead of hnu(CT) ? |I(D) - E(A)|,
      the neutral (N) and ionic (I) states can be defined as follows: (i) the D/A
      materials with DeltaE(H-L)(DA) > 0 (i.e., the LUMO level of A is higher than the
      HOMO level of D) should be neutral, and (ii) complexes adopted when DeltaE(H
      L)(DA) < 0 are, meanwhile, ionic. Materials located near DeltaE(H-L)(DA) ~ 0,
      that is, at the boundary between the N and I phases, are candidates for the N-I
      transition driven by external stimuli such as temperature, pressure, and
      photoirradiation. Even in the ionic state, two distinct states could be isolated
      for the D(2)A type: (ii-1) the 1e(-) transferred D(2)A-MOFs provide mixed-valence
      systems of D(+)D(0)A(-) possibly involving intervalence CT, which produce
      magnetic correlations via radical A(-) units, and (ii-2) when the 2e(-) reduced
      form of A (e.g., TCNQ(2-)) is energetically favored beyond the on-site Coulomb
      repulsion on A, the oxidation state of D(+)(2)A(2-) is produced, for which
      magnetic measurements reveal a paramagnetic state attributed to the isolated D(+)
      units.  The interspatial Coulombic interaction is another factor in determining
      the charge distribution in materials, which is related to the spatial Coulombic
      stability of D/A packing and possibly yields a mixture of N and I domains when it
      is more advantageous to get Coulombic gain than in the uniform N or I phase. Such
      a phase could be observed at the boundary between N and I phases involving the N
      I transition.  These charge-distributed states/phases are systematically
      demonstrated in a D/A-MOF system made by the combination of [Ru(2)(II,II)] and
      TCNQ/DCNQI; however, we immediately recognize the charge distribution of D/A-MOF
      only by understanding the nature of the starting D/A units. The present D/A-MOF
      system should be an intriguing platform to look for new functionalities with
      synergistic correlations among charge, spin, and lattice.

PMID- 23128040
TI  - Adherence with oral oncologic treatment in cancer patients: interest of an
      adherence score of all dosing errors.
AB  - PURPOSE: Patient nonadherence to oral antineoplastic therapy is a well-recognized
      barrier to effective treatment. In order to identify patients who may need
      additional support to become adherent, it is important to have a useful tool that
      takes into account all the parameters of adherence to prescription. The aim of
      this prospective study was to evaluate adherence of oral antineoplastic agents
      and to investigate two calculation methods of adherence score. PATIENTS AND
      METHODS: Twenty-nine cancer patients were enrolled in this study. Fourteen were
      treated by capecitabine and 15 patients by aromatase inhibitors. Adherence was
      measured using a medication event monitoring system and adherence score was
      calculated by a usual method and a composite adherence score that takes into
      account missed doses and also intake interval errors (between 2 doses and between
      meals). RESULTS: Across the 6-month evaluation period, average adherence was 95%
      with the standard calculation (capecitabine group: 89%; aromatase inhibitor
      group: 99%) versus 83% with the composite index (capecitabine group: 62%;
      aromatase inhibitor group: 99%) (p = 0.030). The composite calculation permits to
      highlight more nonadherent patients (29.6 vs. 7.4%), particularly in the
      capecitabine group (73 vs. 18%, p = 0.001). We report 2 cases identified as
      nonadherent with composite adherence rate. CONCLUSION: The composite adherence
      score permits to better evaluate adherence to prescription and to identify
      barriers to adherence and persistence.

PMID- 23128043
TI  - Microchimerism and survival after breast and colon cancer diagnosis.
AB  - Recently, we reported microchimerism to be oppositely associated with maternal
      breast and colon cancer. In women with a blood test positive for male
      microchimerism the risk of breast cancer development was reduced to one third,
      whereas the risk of colon cancer was elevated 4-fold. In this article addendum, I
      report the survival of cases in the original study after being diagnosed with
      cancer. Despite small numbers, the analysis suggests that microchimerism may be
      positively associated with survival after breast and maybe colon cancer
      diagnosis. Despite the findings on colon cancer in our original report, I
      speculate whether microchimerism could have a general beneficial role in cancer,
      which in some sites may not be evident because an allogeneic maternal immune
      reaction hastens cancer development.

PMID- 23128044
TI  - First report of the L1014S kdr mutation in wild populations of Anopheles gambiae
      M and S molecular forms in Burkina Faso (West Africa).
AB  - We investigated the occurrence of the L1014F and L1014S kdr mutations in malaria
      vector populations in Burkina Faso (West Africa). A cross-sectional survey was
      conducted at 10 sites all located in cotton cultivation areas which are assumed
      to be the major insecticide resistance selection foci in Burkina Faso. The hot
      ligation method was used to detect the two kdr mutations in field collected
      Anopheles gambiae s.l. samples. For the first time in Burkina Faso the L1014S
      mutation was identified in both M and S forms of An. gambiae s.s. populations
      collected from the site of Koupela in the central-eastern region at low
      frequency. Furthermore, the L1014S mutation was also found in one specimen of An.
      arabiensis collected from the Dano site. The data generated in this study
      provides additional evidence of the spread of the L1014S mutation into An.
      gambiae s.l. populations in West Africa. It is now important to evaluate the role
      of the L1014S mutation in the pyrethroid resistance phenotype and assess its
      potential impact on the efficacy of pyrethroid-based control measures in West
      Africa where several resistance mutations now coexist.

PMID- 23128046
TI  - Rapid and efficient synthesis of soluble graphene nanosheets using N-methyl-p
      aminophenol sulfate as a reducing agent.
AB  - Mass production of soluble graphene still remains a challenge, although several
      methodologies have been proposed. Here we report a rapid and efficient method for
      the synthesis of soluble graphene nanosheets (GNSs) with long-term dispersion
      stability in both aqueous and common organic solvents. Within only 12 min at 95 
      degrees C, exfoliated graphite oxide in ammonia solution (pH 10) was reduced to
      soluble GNSs using N-methyl-p-aminophenol sulfate (metol) as a reducing agent
      without external stabilizers. The prepared GNSs were characterized by different
      techniques and a comparison of metol and hydrazine hydrate as reducing agents was
      made. The results indicated that, with the advantages of being rapid, efficient,
      inexpensive and relatively environmentally friendly, the reduction of graphite
      oxide into soluble GNSs by metol is a promising substitute for hydrazine hydrate
      in the mass production of soluble GNSs.

PMID- 23128045
TI  - First molecular cloning and gene expression analysis of a teleost CD200 (OX-2)
      glycoprotein from rock bream, Oplegnathus fasciatus.
AB  - CD200 plays an important role in delivering an immunoregulatory signal to the
      immune system through interaction with its receptor. However, CD200 has not been
      characterized and its function in teleosts is unknown. In this study, the rock
      bream (Oplegnathus fasciatus) CD200 gene (RbCD200) was cloned and its expression
      profile was analyzed after infection with Edwardsiella tarda, Streptococcus iniae
      or red seabream iridovirus (RSIV). The coding region of RbCD200 cDNA was 855 bp,
      encoding 284 amino acid residues. The gene consisted of two extracellular Ig-like
      domains and a transmembrane domain. RbCD200 was highly expressed in the brain,
      erythrocytes, intestine and stomach of healthy rock bream. In the spleen, RbCD200
      gene expression was down-regulated until 48 h after E. tarda exposure, except at
      12 h RbCD200 gene expression was down-regulated then up-regulated at 12 h and 24
      h after infection with S. iniae and RSIV, respectively. In the whole kidney, the
      RbCD200 gene was down-regulated in response to infection with E. tarda and S.
      iniae. However, RSIV infection increased RbCD200 gene expression in whole kidney
      until 48 h. These results suggest that RbCD200 is differentially expressed in the
      spleen and whole kidney after infection with different pathogens.

PMID- 23128047
TI  - Fibers come and go: differences in cell-entry components among related dsRNA
      viruses.
AB  - Encapsidated dsRNA viruses, most of which are nonenveloped, infect a wide variety
      of hosts, from bacteria to vertebrates, and are currently grouped into 9 families
      comprising 33 genera. Given this range, it is not surprising that substantial
      diversity is seen in their transmission strategies and cell-entry machineries.
      One interesting set of recent findings is that several of these viruses,
      otherwise closely related, exhibit major differences in their entry machineries
      without comparably major differences in their capsid organizations. Examples are
      presence or absence of receptor-binding fibers among orthoreoviruses and
      aquareoviruses and presence or absence of both binding and membrane-penetration
      modules among totiviruses and between picobirnaviruses and partitiviruses.
      Evolved differences in cell-entry components among these viruses are therefore
      not only common but also seemingly straightforward from a structural standpoint.

PMID- 23128048
TI  - Cognitive decline one year after hospitalization in older adults without
      dementia.
AB  - BACKGROUND/AIMS: We studied cognitive functioning 1 year after hospitalization
      (T2) in patients at least 65 years old without cognitive impairment at baseline
      (T1). METHODS: Cognition was assessed using the Mini-Mental State Examination
      (MMSE) at both time points. We included 211 (114 women) patients with a mean age
      of 78.3 (SD 7.0) years and an MMSE score of 24 and above. RESULTS: At T2, 69
      (32.7%) patients had an MMSE score below 24. In participants with MMSE 24-26 at
      T1, cognitive decline was related to impaired physical self-maintenance, a
      decline in the performance of the instrumental activities of daily living,
      impaired hearing and less reading ability. In participants with MMSE 27-30,
      cognitive decline was associated with higher comorbidity (Charlson Index) and
      impaired physical self-maintenance and hearing. CONCLUSION: A reduced functioning
      level and increased comorbidity predicted a decline in cognitive functioning.

PMID- 23128049
TI  - Renoprotection by continuous erythropoietin receptor activator in puromycin
      aminonucleoside-induced nephrotic syndrome.
AB  - BACKGROUND/AIMS: Recent studies have demonstrated that erythropoiesis-stimulating
      agents (ESAs) induce a tissue-protective effect in the kidney. In this study, we
      examined whether continuous erythropoietin receptor activator (CERA), a long
      acting ESA, could prevent kidney injury, especially podocyte damage, in a rat
      model of nephrotic syndrome induced by puromycin aminonucleoside (PAN). METHODS:
      Rats were injected with CERA (30 ug/kg) or vehicle 4 h before the injection of
      PAN (50 mg/kg). Renal function, kidney injury, and podocyte damage were assessed
      at 7 days. RESULTS: The levels of proteinuria, BUN, and plasma creatinine
      significantly increased in rats with PAN-induced nephrosis. Treatment with CERA
      significantly prevented these deteriorations induced by PAN. Glomerular lesions,
      especially vacuolation of podocytes, and the increase of desmin expression in PAN
      treated rats were significantly ameliorated by treatment with CERA. Treatment
      with CERA also significantly prevented the decrease in the protein productions of
      nephrin and podocin in the kidneys of PAN-treated rats. We found persistent
      activation of the Akt signaling pathway in the kidneys of CERA-treated rats.
      CONCLUSION: CERA could ameliorate renal dysfunction in PAN-induced nephrosis,
      which might be due to the amelioration of podocyte injury. CERA inhibited the
      depletion of nephrin and podocin, key components of the glomerular filtration
      barrier, and alleviated proteinuria. Activation of the Akt signaling pathway
      might be involved in the renoprotective effect of CERA.

PMID- 23128050
TI  - Per-symptomatic brain activations in alcohol-induced hallucinosis.

PMID- 23128051
TI  - Improvements in anorexia symptoms after deep brain stimulation for intractable
      obsessive-compulsive disorder.

PMID- 23128052
TI  - Genetics of ageing-related changes in brain white matter integrity - a review.
AB  - White matter (WM) plays a vital role in the efficient transfer of information
      between grey matter regions. Modern imaging techniques such as diffusion tensor
      imaging (DTI) have enabled the examination of WM microstructural changes across
      the lifespan, but there is limited knowledge about the role genetics plays in the
      pattern and aetiology of age-related WM microstructural changes. Family and twin
      studies suggest that the heritability of WM integrity measures changes over the
      lifespan, with the common DTI measure, fractional anisotropy (FA), showing
      moderate to high heritability in adults. However, few heritability studies have
      been undertaken in older adults. Linkage studies in middle-aged adults suggest
      that specific regions on chromosomes 3 and 15 may harbour genetic variants for WM
      integrity. A number of studies have investigated candidate genes, with the APOE
      E4 polymorphism being the most frequently studied. Although these candidate gene
      studies suggest associations of particular genes with WM integrity measures in
      some specific brain regions, the findings remain inconsistent due to differences
      in their methodologies, samples and the outcome measures used. The APOE E4 allele
      has been associated with decreased WM integrity (FA) in the cingulum, corpus
      callosum and parahippocampal gyrus. Only one genome-wide association study of
      global WM integrity measures in older adults has been published, and reported
      suggestive single nucleotide polymorphisms await replication. Overall, genetic
      age-related WM integrity studies are lacking and a concerted effort to examine
      the genetic determinants of age-related decline in WM integrity is clearly needed
      to improve our understanding of the ageing brain.

PMID- 23128053
TI  - Protein kinase C inhibitor BIM suspended TRPV1 effect on mu-opioid receptor.
AB  - The purpose of the present study was to elucidate the role of protein kinase A
      and C in the mechanism of capsaicin inhibition on mu-opiate receptors. H89, a
      protein kinase A inhibitor and BIM (bisindolylmaleimide), a protein kinase C
      inhibitor were used for this purpose. BIM suspended the inhibition of capsaicin
      in endomorphin-1 competition binding. The addition of BIM alone had no effect
      itself on this reaction. H89 however, exerted a strong inhibitory effect on the
      endomorphin-1 binding. We can conclude that protein kinase C certainly plays a
      role in the inhibition of capsaicin. The role of protein kinase A in this
      reaction could not be established, owing to the blocking effect of H89 on the mu
      opioid receptors.

PMID- 23128054
TI  - Deletion in exon 5 of the SNCA gene and exposure to rotenone leads to
      oligomerization of alpha-synuclein and toxicity to PC12 cells.
AB  - alpha-Synuclein (alpha-syn) is a presynaptic protein that is widely implicated in
      the pathophysiology of Parkinson's disease (PD). Recently, four alpha-syn
      isoforms that are produced by alternative splicing have been described, they are
      alpha-syn140, alpha-syn126, alpha-syn112, and alpha-syn98. The stable cell lines
      which expressed the four alpha-syn isoforms respectively were obtained, and the
      aggregation formation of these alpha-syn isoforms and their associated toxicity
      to PC12 cell were investigated. The results of this study indicate that over
      expression of alpha-syn isoforms alone in dopaminergic cells have no effect on
      the formation of alpha-syn oligomeric species and cell viabilities. When exposed
      to rotenone, these cell lines which over expressed exon 5-lacking form of alpha
      syn isoforms showed the formation of oligomeric species and toxicity to PC12
      cells.

PMID- 23128055
TI  - Associations between urinary excretion of cadmium and proteins in a nonsmoking
      population: renal toxicity or normal physiology?
AB  - BACKGROUND: Associations between cadmium (Cd) and kidney function have been
      reported even at low levels of exposure in the general population. Recently, the
      causality of these associations has been questioned. OBJECTIVES: We examined
      associations between urinary Cd (U-Cd; a biomarker of exposure) and urinary
      proteins that are used as biomarkers of kidney effects, based on repeated short
      term sampling in healthy subjects. METHODS: Twenty-four hour urine samples were
      collected on 2 separate days at six fixed times from 30 healthy nonsmoking men
      and women (median age 39 years). We analyzed the samples (N = 354) for Cd (i.e.,
      U-Cd) and two proteins used as kidney function biomarkers: urinary albumin (U
      Alb) and alpha-1-microglobulin (U-A1M). Concentrations were adjusted for
      creatinine concentration or for specific gravity, and excretion rates (mass per
      hour) were calculated. Possible associations were assessed within each individual
      participant, and mean correlations and regressions were evaluated. RESULTS: We
      found clear positive mean associations within individuals between the excretion
      of U-Cd [mean, 0.11 ug/g creatinine (range, 0.01-0.52 ug/g creatinine)] and both
      U-Alb and U-A1M. The associations were stronger for excretion rates and
      concentrations adjusted for specific gravity than for concentrations adjusted for
      creatinine. We also found significant positive associations of urinary flow with
      excretion of U-Cd, U-Alb, and U-A1M. CONCLUSIONS: Associations between short-term
      changes in U-Cd and markers of kidney function within individual nonsmoking study
      participants are unlikely to reflect effects of Cd toxicity. A more likely
      explanation is that these associations result from normal variation in renal
      function, including changes in urinary flow, that influence the urinary excretion
      of both Cd and proteins in the same direction. These effects of normal
      variability may result in overestimation of the adverse effects of Cd on kidney
      function at low-level Cd exposure.

PMID- 23128056
TI  - Gowers' Queen Square case notes on chorea: a 21st century re-appraisal.
AB  - OBJECTIVE: To analyze the case notes of 127 patients with chorea admitted to the
      National Hospital at Queen Square, London, under the care of William Richard
      Gowers and review his contribution to the study of choreas. METHODS: We consulted
      the case books available at the Queen Square Library, from 1878 to 1911,
      comprising 42 volumes. RESULTS: 97 patients (76.3%) were female and the age of
      presentation ranged from 4 to 60 years (mean 14.3). 43 patients (33.8%)
      experienced recurrent attacks of chorea. 29 patients (22.8%) had a family history
      of chorea. Past history of rheumatic fever was observed in 46 patients (36.2%).
      54 patients (42.5%) had speech impairment while a similar number had a cardiac
      murmur. Generalized chorea occurred in 87.4% and hemichorea in 11.8%. Gowers
      diagnosed different forms of chorea: Huntington's disease, paralytic, persistent,
      recurrent, tetanoid, functional, maniacal, hemichorea and chorea gravidarum.
      CONCLUSIONS: Gowers was one of the pioneers in recognizing chorea as a physical
      sign found in a myriad of etiologies. He also provided a comprehensive
      description of the clinical features and natural history of Sydenham's chorea in
      his work.

PMID- 23128057
TI  - Studying and preventing stillbirth: what are the methodological issues?

PMID- 23128058
TI  - Effects of terlipressin on pulmonary artery pressure in a septic cooled infant:
      an echocardiographic assessment.
AB  - Experience with terlipressin (TP) in the neonatal field is scarce. We describe
      the effects of TP on pulmonary circulation, studied with echocardiography, in an
      asphyxiated septic cooled infant with pulmonary hypertension (PH) who developed
      catecholamine-resistant hypotension and exacerbation of PH shortly after the
      beginning of the rewarming. TP was added to norephinephine and adrenaline
      infusions at the dose of 0.02 mg kg(-1) every 6 h, because of refractory
      hypotension and oliguria. After 10 min, blood pressure dramatically and
      definitely increased, and urinary output was re-established after 60 min.
      Echocardiographic evaluation 30 min after the second bolus of TP showed unchanged
      velocity of the tricuspidal valve regurgitation and improved biventricular
      functional indexes respect to the pre-treatment assessment. TP was continued for
      12 h (three doses) without significant adverse effect except for a transient
      increase in troponin levels. Addition of TP boluses to catecholamine infusion in
      our newborn was effective in increasing systemic vascular resistance without
      increasing pulmonary vascular resistance, successfully reversing the hemodynamics
      of severe PH, and suggesting a potential primary vasodilator effect on pulmonary
      circulation. Transient increase of troponin levels during TP treatment confirms
      the risk of excessive coronary vasoconstriction when TP boluses are added to high
      dose catecholamines.

PMID- 23128059
TI  - The association of molybdenum cofactor deficiency and pyloric stenosis.
AB  - Molybdenum cofactor deficiency (MoCD) is a rare autosomal recessive disorder that
      may present during the neonatal period with intractable seizures. Co-existence of
      MoCD and pyloric stenosis is previously reported as a coincidence or common
      etiology. The etiology of the two conditions is unclear; however, reports
      demonstrate neuronal deficiency in both. We report a neonate who was diagnosed
      with MoCD and hypertrophic pyloric stenosis.

PMID- 23128060
TI  - Tin-mesoporphyrin in the treatment of refractory hyperbilirubinemia due to Rh
      incompatibility.
AB  - We describe the use of tin-mesoporphyrin (SnMP) in the treatment of an infant
      with Rh hemolytic disease. The infant's hyperbilirubinemia responded to
      phototherapy but every time the phototherapy was discontinued, the serum
      bilirubin rebounded and repeat phototherapy was necessary. A single intramuscular
      dose of SnMP on day 18 eliminated the need for further phototherapy and allowed
      us to discharge this infant.

PMID- 23128061
TI  - Functional heartburn:  clinical characteristics and outcome.
AB  - OBJECTIVES: Patients with heartburn and normal upper gastrointestinal endoscopy,
      normal oesophageal acid exposure, no symptom-reflux association and who fail to
      respond to a proton-pump inhibitor are classified as having functional heartburn
      (FH). This study aimed (i) to characterize the symptoms and functional
      abnormalities of patients with FH and (ii) to describe their clinical outcome.
      MATERIALS AND METHODS: Among all patients referred for 24 h multichannel
      intraluminal impedance-pH (MII-pH), patients with FH were identified. The
      clinical characteristics and high-resolution oesophageal pressure topography
      recordings of FH patients were analyzed at the time of the 24-h MII-pH test. A
      symptom-related and health-related quality-of-life questionnaire was then sent to
      FH patients to assess the long-term outcome. RESULTS: Forty patients fulfilled
      the criteria for FH, representing 8.5% of the referred population. Twenty-two
      months after initial testing, 66% of patients still suffered from heartburn. The
      rate of mixed reflux (liquid/gas) was higher in patients with persisting
      heartburn at the final evaluation (63 vs. 50%, P=0.04). Sixty-six per cent of
      patients had one or more manometric abnormalities. Acid clearance time in MII-pH
      was significantly higher in patients with weak peristalsis than patients with
      normal peristalsis (60 +/- 45 vs. 31 +/- 19 s, P=0.03). A high rate of mixed
      reflux and/or a manometric abnormality were associated with a higher risk of
      persistent heartburn. CONCLUSION: FH is a chronic disorder with persisting
      symptoms in two-thirds of patients. An increased rate of mixed reflux and/or the
      presence of manometric abnormalities are associated with a higher risk of
      persisting symptoms and may help to identify the population with unmet
      therapeutic needs.

PMID- 23128062
TI  - Acculturation and drug use disorders among Hispanics in the U.S.
AB  - The authors' objective was to examine the relationship between degree of
      acculturation across five different dimensions of acculturation and risk of drug
      use disorders (DUD) among US Hispanics. Data were derived from a large national
      sample of the US adult population, the National Epidemiological Survey on Alcohol
      and Related Conditions, collected using face-to-face interviews. The sample
      included civilian non-institutionalized U.S. population aged 18 years and older,
      with oversampling of Hispanics, Blacks and those aged 18-24 years. Interviews of
      more than 34,000 adults were conducted during 2004-2005 using the Alcohol Use
      Disorder and Associated Disabilities Interview Schedule - DSM-IV Version. A total
      of 6359 subjects who identified themselves as Hispanics were included in this
      study. Acculturation measures used in this study assessed:, time spent in the
      U.S., age at immigration, language preference, social network composition, and
      ethnic identification. Among Hispanics, there was an inverse relationship between
      five complementary dimensions of acculturation and DUD. Moreover, this
      relationship showed a significant gradient across all acculturation dimensions
      and DUD. The prevalence of DUD increases with acculturation in Hispanics, across
      several measures of acculturation in a dose-response relationship. Hispanic
      cultural features and values exert a protective effect on risk of DUD.
      Preservation and promotion of Hispanic values may be an important component of
      preventive interventions for Hispanics.

PMID- 23128063
TI  - Nucleoside phosphitylation using ionic liquid stabilised phosphorodiamidites and
      mechanochemistry.
AB  - A range of nucleoside phosphoramidites incorporating small amino substituents
      have been readily synthesised using ionic liquid stabilised phosphorodiamidites
      coupled with mechanochemistry.

PMID- 23128064
TI  - Biased versus unbiased randomness in homo-polymers and copolymers of amino acids
      in the prebiotic world.
AB  - The polymerization of amino acids under anhydrous prebiotic conditions was first
      studied several decades ago. Here we use a stochastic model stressing the
      relevant role of the polarity of amino acids in the formation of oligopeptides in
      a prebiotic milieu. Our goal is to outline the predominance of co-polypeptides
      over homo-polypeptides, resulting not only from the randomness, but also from
      polarity properties of amino acids. Our results conclude that there was a higher
      probability of the formation of co-polypeptides than of homo-polymers. Besides,
      we may hypothesize that the former would have a more ample spectrum of possible
      chemical functions than homo-polypeptides.

PMID- 23128065
TI  - The natural history of fetal cells in postpartum murine maternal lung and bone
      marrow: a two-stage phenomenon.
AB  - During pregnancy, fetal cells cross into the maternal organs where they reside
      postpartum. Evidence from multiple laboratories suggests that these microchimeric
      fetal cells contribute to maternal tissue repair after injury. In mouse models,
      most injury experiments are performed during pregnancy; however, in a clinical
      setting most injuries or diseases occur postpartum. Therefore, experiments using
      animal models should be designed to address questions in the time period
      following delivery. In order to provide a baseline for such experiments, we
      analyzed the natural history of fetal cells in the postpartum maternal organs.
      Female C57BL/6J mice were mated to males homozygous for the enhanced green
      fluorescent protein gene. Fetal cells in the maternal lungs and bone marrow were
      identified by their green fluorescence using in a high-speed flow cytometer and
      their counts were compared between the lung and bone marrow. Spearman correlation
      analysis was used to identify relationships between the duration of time
      postpartum and the cell counts and ratio of live and dead cells. Our results show
      that fetal cells persist in these organs until at least three months postpartum
      in healthy female mice. We show a two-stage decline, with an initial two and a
      half-week rapid clearance followed by a trend of gradual decrease. Additionally,
      an increase in the ratio of live to dead cells within the lung over time suggests
      that these cells may replicate in vivo. The results presented here will inform
      the design of future experiments and may have implications for women's health.

PMID- 23128066
TI  - Is bilateral ureterorenoscopy the first choice for the treatment of bilateral
      ureteral stones? An updated study.
AB  - INTRODUCTION: We analyze our recent results and discuss the advantages and
      disadvantages of bilateral single-session ureterorenoscopy (URS) for bilateral
      ureteral stones. PATIENTS AND METHODS: 55 patients underwent URS with pneumatic
      lithotripsy (PL) for bilateral stones. 61 (55.5%), 28 (25.4%) and 21 (19.1%)
      stones were located in the lower, middle and upper ureter, respectively. RESULTS:
      Of the 110 stones, 99 (90.0%) were fragmented in a single procedure. The stone
      clearance rate was 94.5% after the second session. The stone clearance rates with
      regard to stone location were 71.4, 89.3 and 96.7% for the upper, middle and
      lower ureter, respectively. An analysis of the clearance rates based on location
      demonstrated that lower ureteric stones were more successfully removed than upper
      ureteric stones (96.7 vs.71.4%, p = 0.003). CONCLUSION: Bilateral single-session
      URS with PL is a highly effective treatment modality for bilateral ureteral
      stones. The success rate of PL is affected by stone size and location.

PMID- 23128067
TI  - Infection-related cancers in sub-saharan Africa: a paradigm for cancer prevention
      and control.
AB  - There is much commonality between chronic noncommunicable and communicable
      diseases which is best exemplified by cancers of infectious origin. It provides
      the perfect opportunity for harnessing the advances that have been made in the
      control of communicable diseases to attempt the control of noncommunicable
      diseases. There are possibilities at various levels of intervention, at primary,
      secondary and tertiary levels, which fit well within a well-planned national
      cancer control strategy. Prevention should proceed through steps of disruption of
      transmission, improvement in disease recognition and diagnosis, as well as
      through prompt effective treatment. This principle should work for both infection
      and the resultant cancer. Research is very important in understanding how best to
      use the available knowledge and how best to sequentially implement strategies.
      Finally, policies that acknowledge infection-related cancers as a major problem
      in the region should be in place.

PMID- 23128068
TI  - Factors affecting the shape of MBE-grown laterally aligned Fe nanowires.
AB  - Various microstructural and chemical analysis techniques were applied to study
      two types (type-A and B) of self-assembled laterally aligned Fe nanowires (NWs)
      fabricated by molecular beam epitaxy on a ZnS buffer layer. The formation of the
      three-dimensional shapes of these NWs was found to be driven by the principle of
      surface energy minimization. We have provided phenomenological models to address
      the factors affecting the observed topological shape of these NWs, including the
      role of the lattice relationship between the Fe NWs and the underlying buffer
      layer, growth temperature, Fe nominal coverage and substrate orientation.
      Magnetic hysteresis measurements were performed at different temperature,
      demonstrating the Fe NWs possess a coercivity about 30 times larger than that of
      a Fe thin film. The observed gradual magnetization reversal indicates the
      magnetization process is accomplished by the rotation of magnetic moments within
      a single domain.

PMID- 23128069
TI  - Airway-parenchymal interdependence in the lung slice.
AB  - The explanted lung slice has become a popular in vitro system for studying how
      airways contract. Because the forces of airway-parenchymal interdependence are
      such important modulators of airway narrowing, it is of significant interest to
      understand how the parenchyma around a constricting airway in a lung slice
      behaves. We have previously shown that the predictions of the 2-dimensional
      distortion field around a constricting airway are substantially different
      depending on whether the parenchyma is modeled as an elastic continuum versus a
      network of hexagonally arranged springs, which raises the question as to which
      model best explains the lung slice. We treated lung slices with methacholine and
      then followed the movement of a set of parenchymal landmarks around the airway as
      it narrowed. The resulting parenchymal displacement field was compared to the
      displacement fields predicted by the continuum and hexagonal spring network
      models. The predictions of the continuum model were much closer to the measured
      data than were those of the hexagonal spring network model, suggesting that the
      parenchyma in the lung slice behaves like an elastic continuum rather than a
      network of discrete springs. This may be because the alveoli of the lung slice
      are filled with agarose in order to provide structural stability, causing the
      parenchyma in the slice to act like a true mechanical continuum. How the air
      filled parenchyma in the intact lung behave in vivo remains an open question.

PMID- 23128072
TI  - Noninvasive real time tomographic imaging of epileptic foci and networks.
AB  - While brain imaging and electrophysiology play a central role in neuroscience
      research and in the evaluation of neurological disorders, a single noninvasive
      modality that offers both high spatial and temporal resolution is currently not
      available. Here we show in an acute epilepsy rat model that photoacoustic
      tomography (PAT) can noninvasively track seizure brain dynamics with both high
      spatial and temporal resolution, and at a depth that is clinically relevant. The
      noninvasive yet whole surface and depth capabilities of the PAT system allowed us
      to actually see what is happening during ictogenesis in terms of seizure onset
      and spread. Both seizure onset and propagation were tomographically detected at a
      spatial resolution of 150MUm and a temporal resolution of 300ms, respectively.
      The current study lends support to the theory that seizure onset and spread
      involves a rich interplay between multiple cortical and subcortical brain areas
      during the onset and spread of epileptic seizures. Dynamical changes of
      vasculature during epileptiform events were also detected with high
      spatiotemporal resolution. Together, these findings suggest that PAT represents a
      powerful tool for noninvasively mapping seizure onset and propagation patterns,
      and the 'functional' connectivity within epileptic brain networks. 

PMID- 23128070
TI  - Spinal vascular endothelial growth factor (VEGF) and erythropoietin (EPO) induced
      phrenic motor facilitation after repetitive acute intermittent hypoxia.
AB  - Vascular endothelial growth factor (VEGF) and erythropoietin (EPO) exert
      neurotrophic and neuroprotective effects in the CNS. We recently demonstrated
      that VEGF, EPO and their receptors (VEGF-R2, EPO-R) are expressed in phrenic
      motor neurons, and that cervical spinal VEGF-R2 and EPO-R activation elicit long
      lasting phrenic motor facilitation (pMF). Since VEGF, VEGF-R, EPO, and EPO-R are
      hypoxia-regulated genes, and repetitive exposure to acute intermittent hypoxia
      (rAIH) up-regulates these molecules in phrenic motor neurons, we tested the
      hypothesis that 4 weeks of rAIH (10 episodes per day, 3 days per week) enhances
      VEGF- or EPO-induced pMF. We confirm that cervical spinal VEGF and EPO injections
      elicit pMF. However, neither VEGF- nor EPO-induced pMF was affected by rAIH pre
      conditioning (4 wks). Although our data confirm that spinal VEGF and EPO may play
      an important role in respiratory plasticity, we provide no evidence that rAIH
      amplifies their impact. Further experiments with more robust protocols are
      warranted.

PMID- 23128073
TI  - Accurate decoding of sub-TR timing differences in stimulations of sub-voxel
      regions from multi-voxel response patterns.
AB  - We investigated the decoding of ocular dominance stimulations with millisecond
      order timing difference from the blood oxygen level dependent (BOLD) signal in
      human functional magnetic resonance imaging (fMRI). In our experiment, ocular
      dominance columns were activated by monocular visual stimulation with 500- or 100
      ms onset differences. We observed that the event-related hemodynamic response
      (HDR) in the human visual cortex was sensitive to the subtle onset difference.
      The HDR shapes were related to the stimulus timings in various manners: the
      timing difference was represented in either the amplitude of positive peak,
      amplitude of negative peak, delay of peak time, or response duration of HDR.
      These complex relationships were different across voxels and subjects. To find an
      informative feature of HDR for discriminating the subtle timing difference of
      ocular dominance stimulations, we examined various characteristics of HDR
      including response amplitude, time to peak, full width at half-maximum response,
      as inputs for decoding analysis. Using a canonical HDR function for estimating
      the voxel's response did not yield good decoding scores, suggesting that
      information may reside in the variability of HDR shapes. Using all the values
      from the deconvolved HDR also showed low performance, which could be due to an
      over-fitting problem with the large data dimensionality. When using either
      positive or negative peak amplitude of the deconvolved HDR, high decoding
      performance could be achieved for both the 500ms and the 100ms onset differences.
      The high accuracy even for the 100ms difference, given that the signal was
      sampled at a TR of 250ms and 2*2*3-mm voxels, implies a possibility of
      spatiotemporally hyper-resolution decoding. Furthermore, both down-sampling and
      smoothing did not affect the decoding accuracies very much. These results suggest
      a complex spatiotemporal relationship between the multi-voxel pattern of the BOLD
      response and the population activation of neuronal columns. The demonstrated
      possibility of decoding stimulations for columnar-level organization with 100-ms
      onset difference using lower resolution imaging data may broaden the scope of
      application of the BOLD fMRI. 

PMID- 23128074
TI  - Effects of image contrast on functional MRI image registration.
AB  - Lack of tissue contrast and existing inhomogeneous bias fields from multi-channel
      coils have the potential to degrade the output of registration algorithms; and
      consequently degrade group analysis and any attempt to accurately localize brain
      function. Non-invasive ways to improve tissue contrast in fMRI images include the
      use of low flip angles (FAs) well below the Ernst angle and longer repetition
      times (TR). Techniques to correct intensity inhomogeneity are also available in
      most mainstream fMRI data analysis packages; but are not used as part of the pre
      processing pipeline in many studies. In this work, we use a combination of real
      data and simulations to show that simple-to-implement acquisition/pre-processing
      techniques can significantly improve the outcome of both functional-to-functional
      and anatomical-to-functional image registrations. We also emphasize the need of
      tissue contrast on EPI images to be able to appropriately evaluate the quality of
      the alignment. In particular, we show that the use of low FAs (e.g., theta<=40
      degrees ), when physiological noise considerations permit such an approach,
      significantly improves accuracy, consistency and stability of registration for
      data acquired at relatively short TRs (TR<=2s). Moreover, we also show that the
      application of bias correction techniques significantly improves alignment both
      for array-coil data (known to contain high intensity inhomogeneity) as well as
      birdcage-coil data. Finally, improvements in alignment derived from the use of
      the first infinite-TR volumes (ITVs) as targets for registration are also
      demonstrated. For the purpose of quantitatively evaluating the different
      scenarios, two novel metrics were developed: Mean Voxel Distance (MVD) to
      evaluate registration consistency, and Deviation of Mean Voxel Distance (dMVD) to
      evaluate registration stability across successive alignment attempts.

PMID- 23128075
TI  - Individual differences in the proneness to have flow experiences are linked to
      dopamine D2-receptor availability in the dorsal striatum.
AB  - Flow is a subjective experience of high but effortless attention, enjoyment, and
      low self-awareness that can occur during the active performance of challenging
      tasks. The dispositional proneness to experience flow is associated with
      personality traits that are known to be influenced by dopaminergic neural
      systems. Here, for the first time, we investigated relations between flow
      proneness and dopaminergic function. Specifically, we tested the hypothesis that
      the availability of dopamine D2-receptors in the striatum is positively
      associated with flow proneness. Striatal D2-receptor availability was measured in
      a sample of 25 healthy adults using positron emission tomography and
      [(11)C]raclopride. Flow proneness was measured using the Swedish Flow Proneness
      Questionnaire. As hypothesized, there was a significant correlation (r=.41)
      between striatal D2-receptor availability and flow proneness. An exploratory
      analysis of striatal subregions showed that the relation was mainly driven by the
      dorsal striatum, with a significantly higher correlation in the putamen than in
      the ventral striatum. The findings constitute the first demonstration of an
      association between flow proneness and dopaminergic function. We suggest that the
      proneness to experience flow is related to personality dimensions that are under
      dopaminergic control and characterized by low impulsiveness, stable emotion, and
      positive affect.

PMID- 23128076
TI  - Functional segmentation of the hippocampus in the healthy human brain and in
      Alzheimer's disease.
AB  - In this study we segment the hippocampus according to functional connectivity
      assessed from resting state functional magnetic resonance images in healthy
      subjects and in patients with Alzheimer's disease (AD). We recorded the resting
      FMRI signal from 16 patients and 22 controls. We used seed-based functional
      correlation analyses to calculate partial correlations of all voxels in the
      hippocampus relative to characteristic regional signal changes in the thalamus,
      the prefrontal cortex (PFC) and the posterior cingulate cortex (PCC), while
      controlling for ventricular CSF and white matter signals. Group comparisons were
      carried out controlling for age, gender, hippocampal volume and brain volume. The
      strength of functional connectivity in each region also was correlated with
      neuropsychological measures. We found that the hippocampus can be segmented into
      three distinct functional subregions (head, body, and tail), according to the
      relative connectivity with PFC, PCC and thalamus, respectively. The AD group
      showed stronger hippocampus-PFC and weaker hippocampus-PCC functional
      connectivity, the magnitudes of which correlated with MMSE in both cases. The
      results are consistent with an adaptive role of the PFC in the context of
      progression of dysfunction in PCC during earlier stages of AD. Extension of our
      approach could integrate regional volume measures for the hippocampus with their
      functional connectivity patterns in ways that should increase sensitivity for
      assessment of AD onset and progression. 

PMID- 23128077
TI  - Diffusion-weighted magnetic resonance imaging detection of basal forebrain
      cholinergic degeneration in a mouse model.
AB  - Loss of basal forebrain cholinergic neurons is an early and key feature of
      Alzheimer's disease, and magnetic resonance imaging (MRI) volumetric measurement
      of the basal forebrain has recently gained attention as a potential diagnostic
      tool for this condition. The aim of this study was to determine whether loss of
      basal forebrain cholinergic neurons underpins changes which can be detected
      through diffusion MRI using diffusion tensor imaging (DTI) and probabilistic
      tractography in a mouse model. To cause selective basal forebrain cholinergic
      degeneration, the toxin saporin conjugated to a p75 neurotrophin receptor
      antibody (mu-p75-SAP) was used. This resulted in ~25% loss of the basal forebrain
      cholinergic neurons and significant loss of terminal cholinergic projections in
      the hippocampus, as determined by histology. To test whether lesion of
      cholinergic neurons caused basal forebrain, hippocampal, or whole brain atrophy,
      we performed manual segmentation analysis, which revealed no significant atrophy
      in lesioned animals compared to controls (Rb-IgG-SAP). However, analysis by DTI
      of the basal forebrain area revealed a significant increase in fractional
      anisotropy (FA; +7.7%), mean diffusivity (MD; +6.1%), axial diffusivity (AD;
      +8.5%) and radial diffusivity (RD; +4.0%) in lesioned mice compared to control
      animals. These parameters strongly inversely correlated with the number of
      choline acetyl transferase-positive neurons, with FA showing the greatest
      association (r(2)=0.72), followed by MD (r(2)=0.64), AD (r(2)=0.64) and RD
      (r(2)=0.61). Moreover, probabilistic tractography analysis of the septo
      hippocampal tracts originating from the basal forebrain revealed an increase in
      streamline MD (+5.1%) and RD (+4.3%) in lesioned mice. This study illustrates
      that moderate loss of basal forebrain cholinergic neurons (representing only a
      minor proportion of all septo-hippocampal axons) can be detected by measuring
      either DTI parameters of the basal forebrain nuclei or tractography parameters of
      the basal forebrain tracts. These findings provide increased support for using
      DTI and probabilistic tractography as non-invasive tools for diagnosing and/or
      monitoring the progression of conditions affecting the integrity of the basal
      forebrain cholinergic system in humans, including Alzheimer's disease. 

PMID- 23128078
TI  - Temporal properties of shape processing by event-related MEG adaptation.
AB  - Object recognition is a fundamental mechanism of visual processing and requires
      the extraction of shape information. Early visual areas have been linked to the
      analysis of local image features, while higher visual areas of the ventral visual
      pathway rather mediate the perception and recognition of global shapes.
      Investigations of the spatiotemporal characteristics of shape analysis in the
      human visual cortex by rapid event-related fMRI adaptation in combination with a
      region of interest analysis suggested a transient manner of contour integration
      and shape processing in early visual areas compared to sustained processing in
      higher visual areas. fMRI adaptation (or repetition suppression) paradigms offer
      the possibility to enhance the restricted spatial resolution of conventional fMRI
      by focusing on decreased responses for repeated stimulus presentation. However,
      improving our understanding of complex neuronal mechanisms in the human brain
      requires the investigation not only at high spatial but also temporal resolution.
      A limitation of fMRI adaptation can be found in its poor temporal resolution
      which EEG- and MEG-techniques can overcome, though at a lower spatial resolution.
      The present study aimed to investigate temporal characteristics of shape
      processing in the human brain by adapting the principles of fMRI adaption in a
      MEG study. In parallel to an earlier fMRI study, the two stimuli of a trial were
      presented at varied interstimulus intervals. Additional analyses by means of a
      dipole analysis and co-registration of MEG and fMRI data were conducted.
      Adaptation was observed for the short as well as the longer interstimulus
      interval. Interestingly, the latency of the adaptation effects varied with the
      interstimulus interval. The findings support a late onset of adaption that
      possibly underlies global discrimination processes and recognition in higher
      areas of the ventral visual pathway. Further, the present results indicate a
      useful extension of adaptation paradigms and 'region of interest'-analyses from
      fMRI to MEG at a high temporal resolution.

PMID- 23128079
TI  - Dynamic causal modelling of lateral interactions in the visual cortex.
AB  - This paper presents a dynamic causal model based upon neural field models of the
      Amari type. We consider the application of these models to non-invasive data,
      with a special focus on the mapping from source activity on the cortical surface
      to a single channel. We introduce a neural field model based upon the canonical
      microcircuit (CMC), in which neuronal populations are assigned to different
      cortical layers. We show that DCM can disambiguate between alternative (neural
      mass and field) models of cortical activity. However, unlike neural mass models,
      DCM with neural fields can address questions about neuronal microcircuitry and
      lateral interactions. This is because they are equipped with interlaminar
      connections and horizontal intra-laminar connections that are patchy in nature.
      These horizontal or lateral connections can be regarded as connecting
      macrocolumns with similar feature selectivity. Crucially, the spatial parameters
      governing horizontal connectivity determine the separation (width) of cortical
      macrocolumns. Thus we can estimate the width of macro columns, using non-invasive
      electromagnetic signals. We illustrate this estimation using dynamic causal
      models of steady-state or ongoing spectral activity measured using
      magnetoencephalography (MEG) in human visual cortex. Specifically, we revisit the
      hypothesis that the size of a macrocolumn is a key determinant of neuronal
      dynamics, particularly the peak gamma frequency. We are able to show a
      correlation, over subjects, between columnar size and peak gamma frequency - that
      fits comfortably with established correlations between peak gamma frequency and
      the size of visual cortex defined retinotopically. We also considered cortical
      excitability and assessed its relative influence on observed gamma activity. This
      example highlights the potential utility of dynamic causal modelling and neural
      fields in providing quantitative characterisations of spatially extended dynamics
      on the cortical surface - that are parameterised in terms of horizontal
      connections, implicit in the cortical micro-architecture and its synaptic
      parameters. 

PMID- 23128080
TI  - Activation of thalamus in motor imagery results from gating by hypnosis.
AB  - The ability to mentally imagine the performance of automatic movements has been
      well-established being employed in sports and physiotherapy as a tool for motor
      learning and rehabilitation. This is probably mediated by engagement of the same
      brain areas as during real motor performance. Here we investigated the effect of
      hypnotic trance on the cerebral activation pattern engaged in motor imagery in 16
      healthy, right-handed subjects using fMRI. Motor imagery as compared with rest
      was related to activations in the left medial frontal areas (preSMA/SMA),
      prefrontal- and frontal areas, putamen and inferior parietal areas. When compared
      with performance of the same movements motor imagery resulted in activation of
      the left middle frontal cortex, precuneus, and posterior cingulate. Under
      hypnotic trance there was one extra-activation in the left thalamus which
      occurred specifically in the motor imagery condition. The regional beta indices
      were highly correlated among the areas of the cortical-subcortical motor network.
      Our data accord with the notion that hypnotic trance enhances the motor control
      circuit engaged in motor imagery by modulating the gating function of the
      thalamus. 

PMID- 23128081
TI  - fMRI response to blue light delivery in the naive brain: implications for
      combined optogenetic fMRI studies.
AB  - The combination of optogenetics and functional magnetic resonance imaging (fMRI)
      is referred to as opto-fMRI. Optogenetics utilises genetic engineering to
      introduce light sensitive actuator proteins into cells. Functional MRI (fMRI) is
      a specialist form of magnetic resonance imaging concerned with imaging changes in
      blood flow and oxygenation, linked to regional variation in metabolic activity,
      in the brain. This study describes a methodological concern regarding the effects
      of light delivery into the brain for the purposes of opto-fMRI. We show that blue
      light delivery to the naive rat brain causes profound fMRI responses, despite the
      absence of optogenetic activation. We demonstrate that these fMRI responses are
      dependent upon laser power and show that the laser causes significant heating. We
      identify how heating impacts upon the MR signal causing NMR frequency shifts, and
      T1 and T2* changes. This study brings attention to a possible confounder which
      must be taken into account when opto-fMRI experiments are designed. 

PMID- 23128082
TI  - Neural activation during anticipation of opposite-sex and same-sex faces in
      heterosexual men and women.
AB  - Psychobiological accounts of face processing predict that greater salience is
      attributed to faces matching a viewer's sexual preference than to faces that do
      not. However, behaviorally, this effect could only be demonstrated in tasks
      assessing reward 'wanting' (e.g. work-per-view-tasks) but not in tasks assessing
      'liking' (e.g. facial attractiveness ratings), and has been found to be more
      pronounced in heterosexual men than women, especially with regard to very
      attractive faces. Here, we addressed the question if sex differences at the level
      of 'wanting' persist if participants are uninformed about the attractiveness of
      an anticipated male or female face. Seventeen heterosexual men and 13
      heterosexual women (all single) participated in a social incentive delay task
      (SID). Participants were required to react on simple graphical cues in order to
      view a smiling face. Cues provided a priori information on the level of smile
      intensity (low/medium/high) as well as sex of the face (male/ female). A
      significant interaction of sex-of-face and sex-of-participant was observed in a
      priori defined regions of interest in the brain reward system (including ventral
      tegmental area, nucleus accumbens and ventromedial prefrontal cortex), reflecting
      enhanced activation to cues signaling opposite-sex faces relative to same-sex
      faces in both, men and women. Women additionally recruited the temporo-parietal
      junction (TPJ) during processing of opposite- vs. same-sex cues, suggesting
      stronger incorporation of social cognition processes in women than men. The
      findings speak against a general male bias for opposite-sex faces. Instead they
      provide preliminary evidence that men and women recruit different brain circuits
      during reward value assessment of facial stimuli. 

PMID- 23128084
TI  - Dealing with renin-angiotensin inhibitors, don't mind serum creatinine.

PMID- 23128085
TI  - Biotemplated diatom silica-titania materials for air purification.
AB  - We present a novel manufacture route for silica-titania photocatalysts using the
      diatom microalga Pinnularia sp. Diatoms self-assemble into porous silica cell
      walls, called frustules, with periodic micro-, meso- and macroscale features.
      This unique hierarchical porous structure of the diatom frustule is used as a
      biotemplate to incorporate titania by a sol-gel methodology. Important material
      characteristics of the modified diatom frustules under study are morphology,
      crystallinity, surface area, pore size and optical properties. The produced
      biosilica-titania material is evaluated towards photocatalytic activity for NOx
      abatement under UV radiation. This research is the first step to obtain
      sustainable, well-immobilised silica-titania photocatalysts using diatoms.

PMID- 23128087
TI  - Structural probes in quadruplex nucleic acid structure determination by NMR.
AB  - Traditionally, isotope-labelled DNA and RNA have been fundamental to nucleic acid
      structural studies by NMR. Four-stranded nucleic acid architectures studies
      increasingly benefit from a plethora of nucleotide conjugates for resonance
      assignments, the identification of hydrogen bond alignments, and improving the
      population of preferred species within equilibria. In this paper, we review their
      use for these purposes. Most importantly we identify reasons for the failure of
      some modifications to result in quadruplex formation.

PMID- 23128088
TI  - Amplification and re-generation of LNA-modified libraries.
AB  - Locked nucleic acids (LNA) confer high thermal stability and nuclease resistance
      to oligonucleotides. The discovery of polymerases that accept LNA triphosphates
      has led us to propose a scheme for the amplification and re-generation of LNA
      containing oligonucleotide libraries. Such libraries could be used for in vitro
      selection of e.g., native LNA aptamers. We maintained an oligonucleotide library
      encoding 40 randomized positions with LNA ATP, GTP, CTP, and TTP for 7 rounds of
      &#8216;mock&#8217; in vitro selection in the absence of a target and analyzed the
      sequence composition after rounds 1, 4 and 7. We observed a decrease in LNA-A
      content from 20.5% in round 1 to 6.6% in round 7. This decrease was accompanied
      by a substantial bias against successive LNA-As  (poly-LNA adenosine tracts) and
      a relative over-representation of single LNA-As. Maintaining a library with LNA
      TTP yielded similar results. Together, these results suggest that dispersed LNA
      monomers are tolerated in our in vitro selection protocol, and that LNA-modified
      libraries can be sustained for up to at least seven selection rounds, albeit at
      reduced levels. This enables the discovery of native LNA aptamers and similar
      oligonucleotide structures.

PMID- 23128090
TI  - Inhibition of PCAF histone acetyltransferase, cytotoxicity and cell permeability
      of 2-acylamino-1-(3- or 4-carboxy-phenyl)benzamides.
AB  - Small molecule HAT inhibitors are useful tools to unravel the role of histone
      acetyltransferases (HATs) in the cell and they also have relevance in oncology.
      We synthesized a series of 2-acylamino-1-(3- or 4-carboxyphenyl)benzamides 8-19
      bearing C6, C8, C10, C12, C14, and C16 acyl chains at the 2-amino position of 2
      aminobenzoic acid. Enzyme inhibition of these compounds was investigated using in
      vitro PCAF HAT assays. The inhibitory activities of compounds 8-10, 16, and 19
      were similar to that of anacardic acid, and 17 was found to be more active than
      anacardic acid at 100 MUM. Compounds 11-15 showed the low inhibitory activity on
      PCAF HAT. The cytotoxicity of the synthesized compounds was evaluated by SRB
      (sulforhodamine B) assay against seven human cancer cell lines: HT-29 (colon),
      HCT-116 (colon), MDA-231 (breast), A549 (lung), Hep3B (hepatoma), HeLa (cervical)
      and Caki (kidney) and one normal cell line (HSF). Compound 17 was more active
      than anacardic acid against human colon cancer (HCT 116, IC(50): 29.17 MUM),
      human lung cancer (A549, IC50: 32.09 MUM) cell lines. 18 was more active than
      anacardic acid against human colon cancer (HT-29, IC50: 35.49 MUM and HCT 116,
      IC50: 27.56 MUM), human lung cancer (A549, IC50: 30.69 MUM), and human cervical
      cancer (HeLa, IC50: 34.41 MUM) cell lines. The apparent permeability coefficient
      (P(app), cm/s) values of two compounds (16 and 17) were evaluated as 68.21 and
      71.48 * 10-6 cm/s by Caco-2 cell permeability assay.

PMID- 23128091
TI  - Ipomea hederacea Jacq.: a medicinal herb with promising health benefits.
AB  - Ipomea hederacea Jacq. (kaladana or ivy leaf morning-glory), a member of the
      family Convolvulaceae, is used primarily for its seeds and recognized for its
      medicinal properties, especially in Asian countries. This medicinal herb contains
      various valuable chemical constituents such as ecdysteriods, steroidal
      glycosides, aromatic acids, triterpenes, amino acids, organic acids, mineral
      elements and vitamins. A number of pharmacological properties such as diuretic,
      anthelmintic, blood purifier, deobstruent, laxative, carminative and anti
      inflammatory actions have been ascribed to this plant, besides its use to treat
      abdominal diseases, fevers, headache and bronchitis. This review focuses on
      compositional, medicinal and therapeutic properties of this plant, as a potential
      sources of bioactive molecules for medicinal and nutraceutical applications.

PMID- 23128089
TI  - Forward chemical genetics in yeast for discovery of  chemical probes targeting
      metabolism.
AB  - The many virtues that made the yeast Saccharomyces cerevisiae a dominant model
      organism for genetics and molecular biology, are now establishing its role in
      chemical genetics. Its experimental tractability (i.e., rapid doubling time,
      simple culture conditions) and the availability of powerful tools for drug-target
      identification, make yeast an ideal organism for high-throughput phenotypic
      screening. It may be especially applicable for the discovery of chemical probes
      targeting highly conserved cellular processes, such as metabolism and
      bioenergetics, because these probes would likely inhibit the same processes in
      higher eukaryotes (including man). Importantly, changes in normal cellular
      metabolism are associated with a variety of diseased states (including
      neurological disorders and cancer), and exploiting these changes for therapeutic
      purposes has accordingly gained considerable attention. Here, we review progress
      and challenges associated with forward chemical genetic screening in yeast. We
      also discuss evidence supporting these screens as a useful strategy for discovery
      of new chemical probes and new druggable targets related to cellular metabolism.

PMID- 23128092
TI  - Stability computations for isomers of La@C(n) (n = 72, 74, 76).
AB  - Density-functional theory calculations are presented for low-energy La@C72,
      La@C74 and La@C76 isomers with IPR (isolated pentagon rule) and non-IPR cages.
      The relative isomeric production yields at high temperatures are evaluated using
      the calculated terms, and the relationships to observations are discussed.

PMID- 23128093
TI  - Effect of surfactants and manufacturing methods on  the electrical and thermal
      conductivity of carbon nanotube/silicone composites.
AB  - The effect of ionic surfactants and manufacturing methods on the separation and
      distribution of multi-wall carbon nanotubes (CNTs) in a silicone matrix are
      investigated. The CNTs are dispersed in an aqueous solution of the anionic
      surfactant dodecylbenzene sulfonic acid (DBSA), the cationic surfactant
      cetyltrimethylammonium bromide (CTAB), and in a DBSA/CTAB surfactant mixture.
      Four types of CNT-based composites of  various concentrations from 0 to 6 vol.%
      are prepared by simple mechanical mixing and sonication. The morphology,
      electrical and thermal conductivity of the CNT-based composites are analyzed. The
      incorporation of both neat and modified CNTs leads to an increase in electrical
      and thermal conductivity. The dependence of DC conductivity versus CNT
      concentration shows percolation behaviour with a percolation threshold of about 2
      vol.% in composites with neat CNT. The modification of CNTs by DBSA increases the
      percolation threshold to 4 vol.% due to the isolation/separation of individual
      CNTs. This, in turn, results in a significant decrease in the complex
      permittivity of CNT&#8211;DBSA-based composites. In contrast to the percolation
      behaviour of DC conductivity, the concentration dependence of thermal
      conductivity exhibits a linear dependence, the thermal conductivity of composites
      with modified CNTs being lower than that of composites with neat CNTs. All these
      results provide evidence that the modification of CNTs by DBSA followed by
      sonication allows one to produce composites with high homogeneity.

PMID- 23128094
TI  - Spiculisporic acids B-D, three new gamma-butenolide derivatives from a sea urchin
      derived fungus Aspergillus sp. HDf2.
AB  - Three new &#947;-butenolide derivatives 1&#8211;3, named spiculisporic acids
      B&#8211;D, were isolated from the culture of Aspergillus sp. HDf2, a marine
      derived fungus that resides in the sea urchin, Anthocidaris crassispina. The
      structures of 1&#8211;3 were elucidated on the basis of spectroscopic methods,
      including MS and 2D NMR techniques. Their in vitro cytotoxic activities against
      two cell lines (SGC-7901, human gastric adenocarcinoma and SPC-A-1, human lung
      adenocarcinoma) and inhibitory activities against Staphylococcus aureus ATCC
      51650 were investigated.

PMID- 23128095
TI  - Improvement in nerve regeneration through a decellularized nerve graft by
      supplementation with bone marrow stromal cells in fibrin.
AB  - Acellular nerve grafting is often inferior as well as an inadequate alternative
      to autografting for the repair of long gaps in peripheral nerves. Moreover, the
      injection method is not perfect. During the injection of cells, the syringe can
      destroy the acellular nerve structure and the limited accumulation of seed cells.
      To resolve this problem, we constructed a nerve graft by acellular nerve
      grafting. Bone marrow-mesenchymal stromal cells (BM-MSCs) were affixed with
      fibrin glue and injected inside or around the graft, which was then used to
      repair a 15-mm nerve defect in rats. The acellular nerve graft maintained its
      structure and composition, and its tensile strength was decreased, as determined
      by two-photon microscopy and a tensile testing device. In vitro, MSCs embedded in
      fibrin glue survived and secreted growth factors such as nerve growth factor
      (NGF) and brain-derived neurotrophic factor (BDNF). We repaired 15-mm Sprague
      Dawley rat sciatic nerve defects using this nerve graft construction, and MSCs
      injected around the graft helped improve nerve regeneration and functional
      recovery of peripheral nerve lesions as determined by functional analysis and
      histology. Therefore, we conclude that supplying MSCs in fibrin glue around
      acellular nerves is successful in maintaining the nerve structure and can support
      nerve regeneration similar to the direct injection of MSCs into the acellular
      nerve for long nerve defects but may avoid destroying the nerve graft. The
      technique is simple and is another option for stem cell transplantation. 

PMID- 23128096
TI  - Why should we integrate biomarkers into complex trials?.

PMID- 23128097
TI  - BCQ-: a body constitution questionnaire to assess Yin-Xu. Part I: establishment
      of a provisional version through a Delphi process.
AB  - BACKGROUND: Nowadays, the individual differences are emphasized in personalized
      medicine. Traditional Chinese Medicine (TCM) which prescribes tailored treatment
      based on each patient's different body constitution may provide new strategy to
      break the bottleneck of modern medicine (MM). Therefore, to integrate TCM into
      MM, an objective, reliable and rigorous diagnostic tool is necessary for the
      assessment of TCM constitution of each individual. This study aimed to develop a
      provisional version of the Yin-Xu Constitution Questionnaire (BCQ-), because
      evaluating the level of individual's Yin deficiency (Yin-Xu) by his
      manifestations is frequently involved in TCM clinical trials. METHODS: The
      provisional version of BCQ- was developed using a step-by-step approach: 1) to
      form the research team and select a panel of 26 experts who had both MM and TCM
      educational background and professional training for Delphi method; 2) to
      generate questionnaire items from literature review and Delphi process, refine
      these items to be colloquially acceptable, and evaluate their face and content
      validities by Delphi process again; 3) to evaluate the difficulty of answering
      these questions by a pilot study with 81 participants whose age ranged from 20 to
      60 years. RESULTS: After 2 rounds of Delphi process, 22 colloquially appropriate
      questions were established and answered without difficulty by the 81
      participants. CONCLUSIONS: This provisional version of BCQ- appeared to have
      considerable face and content validities and may be the basis to develop an
      advanced Yin-Xu questionnaire. The reliability and validity of BCQ- were further
      tested in the second part of the study.

PMID- 23128098
TI  - Occurrence of chai hu (Bupleuri radix) in prescriptions of Chinese herbal
      medicine in Switzerland.
AB  - BACKGROUND: Chai hu (Bupleuri radix), one of the most frequently used herbs in
      Chinese herbal medicine, has 3 major functions, depending on dosage and
      combination with other herbs. The aim of this study was to investigate how chai
      hu is prescribed in everyday practice in Switzerland, and whether these
      prescription patterns reflect its various applications. METHODS: A random sample
      of 1,053 prescriptions was drawn from the database of Lian Chinaherb AG,
      Wollerau, Switzerland, and analyzed regarding the most frequently used classical
      formulas containing chai hu, daily dosages and combinations with other herbs.
      RESULTS: 29.0% of all prescriptions contained chai hu, and 98.0% of these were in
      granular form. The most frequently used classical formulas were xiao yao san
      ('rambling powder'), jia wei xiao yao san ('augmented rambling powder') and chai
      hu shu gan san ('Bupleurum powder to spread the liver'). In more than half of the
      prescriptions, chai hu was combined with bai shao (Paeoniae Radix Alba), dang gui
      (Angelicae sinensis radix) or fu ling (Poria). 51.8% of the prescriptions
      contained a low daily dosage of chai hu, 24.9% a medium and 15.1% a high dosage.
      CONCLUSION: Chai hu was generally prescribed in classic combinations with other
      herbs and in a medium dosage. Due to the addition of supplementary herbs to
      classical formulas, its daily dose was often diminished from a high or medium
      dose to a low dose. This raises the question if chai hu would then still exert
      its desired function of, e.g., moving liver-qi in these prescriptions.

PMID- 23128099
TI  - Short-term effect of macronutrient composition and glycemic index of a yoghurt
      breakfast on satiety and mood in healthy young men.
AB  - BACKGROUND: Promoting satiety and repressing appetite is one major goal in the
      dietetic therapy of obesity. In the past, several studies investigated the effect
      of different macronutrients, especially protein and carbohydrates, on short- and
      long-term satiety in humans. This paper aims to directly compare the effect of
      protein, rolled oats (low glycemic index), sugar or cornflakes (high glycemic
      index), and walnuts (high amount of omega-3 fatty acids) as ingredients of a
      yoghurt breakfast on short-term hunger and satiety in one setting. A second
      objective was to study the effect of these yoghurt breakfasts on mental state.
      METHODS: 14 healthy male volunteers participated in this randomized, controlled,
      cross-over design study. After consuming the different test meals, volunteers
      repeatedly completed 2 questionnaires over a total of 3 h. RESULTS: The protein
      meal showed the highest satiety scores and the controls (low-calorie yoghurt) the
      lowest. The other test meals were not different among each other. Regarding
      mental state (mood, fatigue, and calmness), no significant difference between the
      test meals and the low-calorie control was observed. CONCLUSION: The glycemic
      index does not seem to modify satiety in this short-term setting. The similar
      mental state between low- and high-calorie breakfasts deserves further
      investigations.

PMID- 23128100
TI  - The role of empathy in therapy and the physician-patient relationship.
AB  - This paper seeks to give an overview of the role of clinical empathy in therapy
      and in the physician-patient relationship. Researchers have offered definitions
      of empathy in the clinical context, and a number of validated measures exist.
      There is evidence from the health-related research literature to support the
      positive association of clinical empathy with improved therapeutic outcomes in a
      wide range of clinical settings. Clinical empathy is also understood to be a
      crucial component of the physician-patient therapeutic relationship. Barriers to
      the development and expression of empathy in the clinical context are explored,
      and ways of enhancing empathy discussed.

PMID- 23128101
TI  - [Emergency treatment of epilepsy with Yamamoto New Scalp Acupuncture (YNSA) and
      body acupuncture - acupuncture in emergency medicine: a case report].
AB  - BACKGROUND: Worldwide, acupuncture is used in conflict areas and increasingly
      also as a supportive measure in emergency medicine. METHODS: In this case, the
      treatment of epilepsy, masseter cramp, unconsciousness and respiratory arrest by
      means of YNSA and body acupuncture with only 3 acupuncture needles is described.
      The 3 points used were YNSA basal ganglia point, Renzhong and Qiangu. RESULTS:
      After application of the needles, the epileptic fit stopped, the unconscious
      patient opened his mouth and started breathing spontaneously. CONCLUSION: In this
      case, acupuncture simplified the emergency procedure as a supportive treatment
      method and provided the patient with fast and safe relief.

PMID- 23128102
TI  - Neuropsychiatric symptoms and executive functioning in patients with mild
      cognitive impairment: relationship to caregiver burden.
AB  - BACKGROUND: Caregivers of patients with mild cognitive impairment (MCI) need
      similar levels of support services as Alzheimer's disease (AD) caregivers, but it
      is unclear if this translates to increased caregiver burden. METHODS: 135
      participants and their caregivers (40 MCI, 55 AD and 40 normal controls, NC)
      completed questionnaires, and the patients were administered neuropsychological
      tests. RESULTS: The MCI caregivers reported significantly more overall caregiving
      burden than the NC, but less than the AD. They showed similar levels of
      emotional, physical and social burden as the AD caregivers. Among the MCI
      caregivers, the neuropsychiatric symptoms and executive functioning of the
      patients were related to a greater burden, and the caregivers with a greater
      burden reported lower life satisfaction and social support, and a greater need
      for support services. CONCLUSION: These results indicate that MCI caregivers are
      at increased risk for caregiver stress, and they require enhanced assistance
      and/or education in caring for their loved ones.

PMID- 23128103
TI  - Relationship between the expression of the extracellular matrix genes SPARC,
      SPP1, FN1, ITGA5 and ITGAV and clinicopathological parameters of tumor
      progression and colorectal cancer dissemination.
AB  - OBJECTIVE: To evaluate the relationship between the expression of the
      extracellular matrix (ECM) genes SPARC, SPP1, FN1, ITGA5 and ITGAV and the
      histopathologic parameters of neoplastic progression and colorectal carcinoma
      (CRC) dissemination. METHODS: A retrospective study was conducted in 114 patients
      with stage I-IV CRC who underwent primary tumor resection. Quantitative real-time
      PCR and immunohistochemistry (IHC) assays were performed in samples obtained from
      the primary tumors. The correlation between the expression of these markers and
      the expression of p53, Bcl-2, Ki67, epidermal growth factor receptor (EGFR) and
      vascular endothelial growth factor was assessed with the Spearman coefficient
      (r). RESULTS: The ITGAV gene was found to be significantly amplified in tumors
      with positive perineural invasion (p = 0.028). Expression of the SPARC, SPP1,
      FN1, ITGA5 and ITGAV genes did not correlate with TNM staging. A direct
      relationship between ITGAV and EGFR expression (r = 0.774; p < 0.001) was
      observed by IHC. CONCLUSIONS: ECM gene expression did not correlate with
      classical prognostic factors for CRC, but overexpression of the ITGAV gene and
      protein was correlated with an increased risk of perineural invasion. The
      relationship between ITGAV and EGFR expression suggests the possibility of
      crosstalk in this signal pathway.

PMID- 23128109
TI  - Biomarkers of epithelial-mesenchymal transition in squamous cell carcinoma.
AB  - An understanding of the process by which tumor cells destroy the basement
      membrane of the surface epithelium, invade, and metastasize is essential to the
      development of novel treatment of head and neck squamous cell carcinoma (HNSCC).
      In recent years, there has been increased interest in the role of epithelial
      mesenchymal transition (EMT) in invasion. EMT is a process that describes the
      development of motile, mesenchymal-like cells from non-motile parent epithelial
      cells. There are 3 known types of EMT that mediate development, wound healing,
      and carcinogenesis. This review summarizes studies of known EMT biomarkers in the
      context of HNSCC progression. The biomarkers discussed come from a wide range of
      proteins, including cell-surface proteins (E-cadherin, N-cadherin, and
      Integrins), cytoskeletal proteins (alpha-Smooth Muscle Actin, Vimentin, and beta
      catenin), extracellular matrix proteins (Collagens, Fibronectin, and Laminin),
      and transcription factors (SNAIL1, SNAIL2, TWIST, and LEF-1). Overall, the
      findings of these studies suggest that EMT mediates HNSCC progression. The
      mechanistic role of the EMT markers that have been associated with HNSCC should
      be more clearly defined if new anti-HNSCC therapies to block EMT progression are
      to be developed.

PMID- 23128112
TI  - Is podocyte research at a tipping point? Report from the 9(th) International
      Podocyte Conference.

PMID- 23128110
TI  - Effects of etch-and-rinse and self-etch adhesives on dentin MMP-2 and MMP-9.
AB  - Auto-degradation of collagen matrices occurs within hybrid layers created by
      contemporary dentin bonding systems, by the slow action of host-derived matrix
      metalloproteinases (MMPs). This study tested the null hypothesis that there are
      no differences in the activities of MMP-2 and -9 after treatment with different
      etch-and-rinse or self-etch adhesives. Tested adhesives were: Adper Scotchbond
      1XT (3M ESPE), PQ1 (Ultradent), Peak LC (Ultradent), Optibond Solo Plus (Kerr),
      Prime&Bond NT (Dentsply) (all 2-step etch-and-rinse adhesives), and Adper Easy
      Bond (3M ESPE), Tri-S (Kuraray), and Xeno-V (Dentsply) (1-step self-etch
      adhesives). MMP-2 and -9 activities were quantified in adhesive-treated dentin
      powder by means of an activity assay and gelatin zymography. MMP-2 and MMP-9
      activities were found after treatment with all of the simplified etch-and-rinse
      and self-etch adhesives; however, the activation was adhesive-dependent. It is
      concluded that all two-step etch-and-rinse and the one-step self-etch adhesives
      tested can activate endogenous MMP-2 and MMP-9 in human dentin. These results
      support the role of endogenous MMPs in the degradation of hybrid layers created
      by these adhesives.

PMID- 23128114
TI  - Enhanced induction of Cyp24a1 by FGF23 but low serum 24,25-dihydroxyvitamin D in
      CKD: implications for therapy.
AB  - In normal people, induction by FGF23 of renal Cyp24a1, the enzyme that degrades
      25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, helps to protect from the
      disorders caused by excessive 1,25-dihydroxyvitamin D. Dai and co-workers report,
      however, that in human and mouse kidney disease, high FGF23 concurs with low
      rather than high serum 24,25-dihydroxyvitamin D, a biomarker of Cyp24a1 activity.
      Their characterization of the underlying mechanisms provides new understanding of
      how kidney disease impairs the health benefits of vitamin D-FGF23/klotho
      interactions.

PMID- 23128116
TI  - A defect in vasopressin secretion in autosomal dominant polycystic kidney
      disease.
AB  - A nephrogenic defect in urine concentration is well established in patients with
      polycystic kidney disease, but Ho et al. report a defect in the increase of
      plasma vasopressin in response to dehydration. On a cellular level, transient
      receptor potential channels responsible for osmoperception could interact with
      TRPPs encoded by the polycystic genes PKD1 and PKD2.

PMID- 23128115
TI  - A new 'tac' for childhood nephrotic syndrome.
AB  - Calcineurin inhibitors (CNIs) are frequent first-line agents in children with
      steroid-resistant nephrotic syndrome (SRNS). However, limited randomized
      controlled trial (RCT) data are available comparing CNIs with alternative
      therapies. Gulati and colleagues report their experience with tacrolimus versus
      cyclophosphamide in childhood SRNS. Their results establish clear superiority of
      tacrolimus over cyclophosphamide and give further proof that RCTs in childhood
      SRNS are both feasible and vital for improving the standard of care.

PMID- 23128117
TI  - On the obituary for George E. Schreiner.

PMID- 23128104
TI  - Fish oil and postoperative atrial fibrillation: the Omega-3 Fatty Acids for
      Prevention of Post-operative Atrial Fibrillation (OPERA) randomized trial.
AB  - CONTEXT: Postoperative atrial fibrillation or flutter (AF) is one of the most
      common complications of cardiac surgery and significantly increases morbidity and
      health care utilization. A few small trials have evaluated whether long-chain n-3
      polyunsaturated fatty acids (PUFAs) reduce postoperative AF, with mixed results.
      OBJECTIVE: To determine whether perioperative n-3-PUFA supplementation reduces
      postoperative AF. DESIGN, SETTING, AND PATIENTS: The Omega-3 Fatty Acids for
      Prevention of Post-operative Atrial Fibrillation (OPERA) double-blind, placebo
      controlled, randomized clinical trial. A total of 1516 patients scheduled for
      cardiac surgery in 28 centers in the United States, Italy, and Argentina were
      enrolled between August 2010 and June 2012. Inclusion criteria were broad; the
      main exclusions were regular use of fish oil or absence of sinus rhythm at
      enrollment. INTERVENTION: Patients were randomized to receive fish oil (1-g
      capsules containing >=840 mg n-3-PUFAs as ethyl esters) or placebo, with
      preoperative loading of 10 g over 3 to 5 days (or 8 g over 2 days) followed
      postoperatively by 2 g/d until hospital discharge or postoperative day 10,
      whichever came first. MAIN OUTCOME MEASURE: Occurrence of postoperative AF
      lasting longer than 30 seconds. Secondary end points were postoperative AF
      lasting longer than 1 hour, resulting in symptoms, or treated with cardioversion;
      postoperative AF excluding atrial flutter; time to first postoperative AF; number
      of AF episodes per patient; hospital utilization; and major adverse
      cardiovascular events, 30-day mortality, bleeding, and other adverse events.
      RESULTS: At enrollment, mean age was 64 (SD, 13) years; 72.2% of patients were
      men, and 51.8% had planned valvular surgery. The primary end point occurred in
      233 (30.7%) patients assigned to placebo and 227 (30.0%) assigned to n-3-PUFAs
      (odds ratio, 0.96 [95% CI, 0.77-1.20]; P = .74). None of the secondary end points
      were significantly different between the placebo and fish oil groups, including
      postoperative AF that was sustained, symptomatic, or treated (231 [30.5%] vs 224
      [29.6%], P = .70) or number of postoperative AF episodes per patient (1 episode:
      156 [20.6%] vs 157 [20.7%]; 2 episodes: 59 [7.8%] vs 49 [6.5%]; >=3 episodes: 18
      [2.4%] vs 21 [2.8%]) (P = .73). Supplementation with n-3-PUFAs was generally well
      tolerated, with no evidence for increased risk of bleeding or serious adverse
      events. CONCLUSION: In this large multinational trial among patients undergoing
      cardiac surgery, perioperative supplementation with n-3-PUFAs, compared with
      placebo, did not reduce the risk of postoperative AF. TRIAL REGISTRATION
      clinicaltrials.gov Identifier: NCT00970489.

PMID- 23128119
TI  - Aldosterone blockade: the heart versus the kidney.

PMID- 23128121
TI  - Urea handling in acute renal failure.

PMID- 23128122
TI  - Parathyromatosis.

PMID- 23128123
TI  - The Case: diabetic nephropathy in a nondiabetic smoker?

PMID- 23128124
TI  - Low-temperature growth of multiple-stack high-density ZnO nanoflowers/nanorods on
      plastic substrates.
AB  - Reported here is the low-temperature growth of multiple-stack high-density ZnO
      nanoflower/nanorod structures on polyethylene naphthalate (PEN) substrates
      derived from the surface modification of ZnO seed layers using an atmospheric
      pressure plasma jet (APPJ) treatment. The plasma treatment could provide several
      advantages to the growth of multiple-stack ZnO nanoflower/nanorod structures: (i)
      the surface wettability of the seed layers changes from hydrophobic to
      hydrophilic, resulting in higher surface energies for the growth of high-density
      ZnO nanoflowers, (ii) the nucleation sites increase due to the increased surface
      roughness caused by the plasma etching, and (iii) there is no thermal damage to
      the plastic substrate from the plasma treatment due to its low-temperature weakly
      ionized discharge. It was also confirmed that multiple stacks of ZnO nanoflowers
      were obtained without degradation of the crystal quality or modification to the
      crystal shape or phase. The ZnO nanoflower/nanorod structures grew by lengths up
      to 4 MUm due to an increased surface roughness of 10% and surface energy 5.5
      times that of the seed layers. As shown, the APPJ is a very good method to obtain
      high-density ZnO nanostructures on plastic substrates below 150  degrees C, as is
      critical for flexible electronics.

PMID- 23128125
TI  - Prevalence and correlates of posttraumatic stress in parents of young children
      postburn.
AB  - This study examined the prevalence and correlates of posttraumatic stress
      symptoms (PTSS) in the parents of very young children who sustained a minor to
      moderate size burn injury. Although prior research has explored this relationship
      in families of children with major burns, only minimal research has focused on
      children with minor to moderate injuries. Forty-five parents of young children
      (<6 years) with a burn injury (mean TBSA = 2.67%, SD = 2.40) completed
      questionnaires regarding PTSS and demographics at an outpatient burn clinic.
      Injury-related information was collected from medical records. Parents reported
      clinically significant levels of PTSS, although in most cases, full diagnostic
      criteria for posttraumatic stress disorder were not met. The amount of distress
      was related to the age of the child at burn, child PTSS, and the source of burn.
      Variables such as size of burn, days spent as inpatient, or parental presence at
      the time of burn were not found to be related to parental distress. PTSS
      assessment should be made mandatory for all parents of young children
      experiencing a burn injury, regardless of size and severity of burn or parental
      presence at the time of burn.

PMID- 23128127
TI  - The impact of caregiver support on mortality following burn injury in the
      elderly.
AB  - Advances in burn care have decreased mortality in the past 20 years, but
      affecting elderly mortality rates (>65 years) remain challenging. This study
      evaluates the impact of home caregiver support on elderly burn patients'
      mortality. The authors retrospectively reviewed patients aged 65 and older
      admitted to their burn center from July 1995 to October 2004. Patient
      demographics, Injury Severity Score, TBSA, and patients' primary caregiver were
      collected. The outcomes were mortality, disposition, and length of stay and these
      were evaluated using univariate and subsequently multivariate regression.
      Significance was calculated at P <= .05. A total of 112 patients were included in
      the analysis. The mean age was 76+/-8. Male patients constituted 47%, whereas 53%
      were female patients, and mean TBSA was 21+/-16%. Thirty patients' primary
      caregiver was a spouse, for 38 it was a child, and 44 had no caregiver. Fifty
      eight patients survived (51.7%), and 54 patients died (48.3%). Only 21% of the
      survivors had a child as their primary caregiver; however, 48% of the
      nonsurvivors had a child as the primary caregiver (P <= 0.05). On multivariate
      analysis, age, TBSA, and child as primary caregiver were all independent
      predictors of mortality. Having a child as a caregiver provided the largest
      impact, with an odds ratio of 4.4 (95% confidence interval, 1.2-15.62; P = .02).

PMID- 23128126
TI  - DNA and inflammatory mediators in bronchoalveolar lavage fluid from children with
      acute inhalational injuries.
AB  - The aim of this study was to assess the feasibility of using serial
      bronchoalveolar lavage fluids (BALFs) to characterize the course of cell damage
      and inflammation in the airways of pediatric patients with acute burn or
      inhalation injury. This was a prospective, longitudinal, descriptive pilot study
      conducted at the Burn and Pediatric Intensive Care Units in a tertiary care
      medical center. Six consecutively intubated and mechanically ventilated pediatric
      patients with acute inhalational injuries were studied. Serial BALF specimens
      from clinically indicated bronchoscopies were used to measure DNA and cytokine
      levels. BALF DNA levels for the six pediatric burn subjects were the highest
      within the first 72 hours after burn injury and declined thereafter. At the early
      stages after injury, BALF DNA levels (median [min, max] 3789 [1170, 11,917]
      ng/ml) were similar to those in adult burn patients and pediatric cystic fibrosis
      or bronchiectasis patients and was higher than those in pediatric recurrent
      pneumonia patients. BALF DNA levels in children and adults with inhalation injury
      correlated significantly with BALF interleukin-6, interleukin-8, and transforming
      growth factor-beta1 levels. The patient with the most severe early visible airway
      mucosal damage and soot pattern at bronchoscopy, as well as the most extensive
      burns, also had the highest average early BALF DNA level (11,917 ng/ml) and the
      longest ventilator course and hospital stay. Procedures were well tolerated. In
      children with acute burn and inhalational injury, airway cellular damage and
      inflammation (reflected in high BALF DNA levels) appear to peak during the first
      72 hours after burn or inhalation injury followed by a slow decline. Serial
      analysis of factors in airway secretions is feasible and has the potential to
      reveal important pathophyisiologic pathways and therapeutic targets for the
      treatment of acute inhalational injuries.

PMID- 23128128
TI  - Progression of wound pH during the course of healing in burns.
AB  - The aim of this study was to measure the pH on the wound surface of 30 burn
      patients and test the hypothesis that wound surface pH is correlated to healing
      time and burn depth. Inclusion criteria were any adult outpatient with burn
      injury. Patient age was 17 to 75 years (mean, 44), burn depth ranged from
      superficial to full thickness with a TBSA of 0.4 to 4%. Cause of burn included
      scalds, flame burn, and contact burns. On admission, and at each dressing change,
      the pH on the wound surface was measured. The pH in both healing and nonhealing
      wounds was found to decrease with each dressing change. At the second dressing
      change, wounds that went on to heal were found to have a significantly lower pH
      of 7.32 in comparison with pH 7.73 in wounds that failed to heal and therefore
      required subsequent grafting (P = .004). Wound pH was also correlated to depth at
      the second dressing change (superficial = pH 6.05, full thickness = pH 8.0). The
      correlation between pH and wound outcome could be used as an additional
      diagnostic tool to predict poor healing in wounds. Early identification of a
      nonhealing wound may allow a more aggressive treatment regimen, including skin
      grafting, to bring about rapid wound healing.

PMID- 23128129
TI  - Application of crystalline cellulose membrane (Veloderm) on split-thickness skin
      graft donor sites in burn or reconstructive plastic surgery patients.
AB  - The present study was performed in China to compare the efficacy and safety of an
      advanced wound dressing made of crystalline cellulose (Veloderm) to a
      conventional treatment of three Vaseline gauzes in the management of skin donor
      sites of burns or reconstructive plastic surgery. In this prospective,
      multicenter, open-labeled, randomized clinical trial performed in three Chinese
      burn centers in China, 96 patients who required autologous split skin graft were
      randomized into either the test (Veloderm) group or the control (Vaseline gauze)
      group. Average healing times in the test group and in the control group were
      8.40+/-2.90 and 8.92+/-2.58 days, respectively, with median values of 7.00 and
      8.00 days, respectively: the difference between two groups was statistically
      significant (P=.045). Scores for exudates, pain intensity, and peripheral
      erythema showed no difference between the groups; however, composite scores of
      three variables on day 10 postoperatively was significantly lower in the test
      group (0.00+/-0.00 vs. 0.13+/-0.49; P = .043). The need for a dressing change was
      also significantly lower in the test group (12.5 vs. 31.25%; P = .036). Veloderm
      is a safe and effective dressing that may offer some advantages over the
      traditional application of Vaseline gauze in the management of donor sites in
      burn or reconstructive plastic surgery patients.

PMID- 23128130
TI  - Albumin supplementation for hypoalbuminemia following burns:  unnecessary and
      costly!
AB  - Following fluid resuscitation, patients with major burns frequently develop
      prolonged hypoalbuminemia. It is not known whether this should be corrected by
      albumin supplementation. The purpose of this study was to determine whether there
      are any benefits associated with albumin supplementation to correct
      hypoalbuminemia in burned adults. We conducted a retrospective comparison of
      patients with burns >= 20% TBSA admitted to an adult regional American Burn
      Association-verified burn center, from May 1, 2009, to September 30, 2010, where
      we did not routinely supplement albumin (control group), with patients admitted
      from October 1, 2010, to May 30, 2011, where we had instituted a protocol in
      which 5% human albumin was provided to maintain serum albumin levels >20 g/L
      (albumin group). Comparisons were made from postburn (PB) day 2 to day 30
      inclusive. There were no significant differences between control (n = 26) and
      albumin (n = 17) in age (48 +/- 15 vs 45 +/- 21 years; P = .56), burn size (33 +/
      13 vs 34 +/- 13 %TBSA; P = .831), or full thickness burn size (19 +/- 19 vs 23
      +/- 19 %TBSA; P = .581). Inhalation injury was significantly more frequent in the
      albumin group than in controls (71% vs 31%; P = .01). The groups did not differ
      significantly in need for admission escharotomy, admission Sequential Organ
      Failure Assessment (SOFA) score, number of surgical procedures/first 30 days, or
      24 and 48 hours fluid resuscitation volume requirements. The overall mean daily
      serum albumin level from PB day 2 to 30 in the albumin group (26.9 +/- 3.0 g/L)
      was significantly greater than in controls (21.9 +/- 4.4 g/L; P < .001). There
      were no significant differences between the groups in daily SOFA score/first 30
      days, peak SOFA score, DeltaSOFA, hospital length of stay, time to wound healing,
      duration of mechanical ventilation, or 30-day and in-hospital mortality. The cost
      of routinely supplementing 5% albumin between PB day 2 to 30 in the albumin group
      was more than four times that for the controls where we did not routinely provide
      albumin (Can $65.50 vs Can $16.57 per patient per day). We conclude that routine
      supplementation of 5% human albumin to maintain a serum albumin level >= 20 g/L
      in burn patients is expensive and provides no benefit.

PMID- 23128131
TI  - An unusual burn caused by toner powder.

PMID- 23128132
TI  - An unusual burn during routine magnetic resonance imaging.
AB  - Burn injuries are known to occur from magnetic resonance imaging. Prevention
      efforts focus on avoiding internal and external metallic objects from contacting
      the patient's tissue during image acquisition. Despite rigorous screening,
      however, there is a subset of thermal injuries that can occur through the
      formation of closed loops of current within the patient. This case report
      describes an example of this uncommon type of injury as well as a successful,
      nonoperative management approach. Given the frequent use of magnetic resonance
      imaging, we report this rare case to raise awareness of this mechanism of injury
      and its treatment.

PMID- 23128133
TI  - A validity review of the National Burn Repository.
AB  - Health-related registries arose because of clinicians' desires to improve patient
      quality of care for a specific disorder. As such, disease registries differ from
      administrative registries in concept, organization, purpose, data recording, and
      results. Because of their voluntary nature, health-related disease registries are
      not regularly audited, have a narrow focus, and are designed for clinicians, not
      administrators. As part of a Department of Defense initiative, we conducted an
      intensive qualitative review of the American Burn Association's National Burn
      Repository (NBR). Our objectives are to inform future users of the NBR of issues
      that could affect statistical analyses and inferences and assist efforts to
      improve data collection. We obtained a deidentified copy of the 2009 release of
      the NBR containing 286,293 records. We reviewed this data set for 1) records
      lacking vital patient information (age, burn size, survival, gender); 2)
      inconsistencies between data in different fields of the database; and 3)
      duplicate values. By restricting our review to records with an admission year of
      2000 or later, we found that vital patient information was missing or invalid for
      about 60,000 records. Data inconsistencies were found in hospital admission
      status (initial admission or readmission) for about 12,000 records, survival for
      about 950 records, and burn injury for about 5500 records. Depending on the
      criterion used to identify duplicate records, we found at least 4000 duplicate
      records but as many as 14,000 in the database. Finally, significant data quality
      issues were found for facilities not using the Trauma Registry for the American
      College of Surgeons (TRACS) software. All health-related disease registries,
      unlike administrative databases, are voluntary. Anonymity of data is vital, and
      data auditing and reporting are challenging. The data contained in the NBR is
      disease-specific, and, as such, has the potential to provide valuable
      epidemiologic, treatment, and outcome data as reported by clinicians, not
      registrars. The NBR provides substantive data on burn injury; however, data
      review needs to precede data analysis. Revisions to NBR data collection have
      improved the quality of data submitted, yet data quality issues remain in the
      current database. Investigators are cautioned to thoroughly assess all fields
      before conducting analyses using the NBR.

PMID- 23128134
TI  - Human red blood cells contain antifibrogenic factors that stimulate MMP-1
      expression in dermal fibroblasts.
AB  - The healing of a burn injury is a dynamic biological process, and there must be a
      set of factors that gradually slow down and/or terminate this healing process
      upon epithelialization. We have previously demonstrated that some members of the
      14-3-3 protein family including stratifin, which is mainly released by
      differentiated keratinocytes, have a potent matrix metalloproteinase-1 (MMP-1), 
      3, -8, and -24 stimulatory effect for fibroblasts. During the course of our
      studies, we discovered that human red blood cells (RBCs) contain a high level of
      different 14-3-3 isoforms. In this study, we evaluated the presence of these
      proteins in RBC and examined the efficacy of RBC in stimulating the expression of
      MMP-1 in dermal fibroblasts using Western blot analysis. The findings revealed
      the presence of all seven isoforms of 14-3-3 (eta, gamma, epsilon, sigma, beta,
      zeta, and tau) in RBC lysate, though with different levels of expression.
      Interestingly, the levels of some of these proteins were higher in RBC from new
      born babies compared to those of adults. We also found that RBC lysate
      significantly increased the expression of MMP-1 in different strains of
      fibroblasts, and this effect has been abrogated by almost 20% when R18 was used
      to deplete the 14-3-3 proteins from lysate. However, when RBC lysate was passed
      through a 3-kDa filter, and then whole RBC lysate, retentate, and filtrate were
      used to treat three strains of fibroblasts, MMP-1 expression was increased
      significantly, indicating the presence of MMP-1-inducing factors smaller than
      3kDa in RBC lysate as well. The MMP-1 stimulatory effect of RBC lysate for
      fibroblasts was stable at freeze/thawing as well as freezing for at least 1 year.
      In conclusion, the MMP-1 stimulatory effect of RBC lysates might play an
      important role in the regulation of extracellular matrix under physiological and
      pathological conditions. Because of its MMP-1 stimulating effect, the RBC lysate
      might be used as an antifibrogenic factor for the treatment of some
      fibroproliferative conditions such as hypertrophic scarring and keloid.

PMID- 23128135
TI  - Effectiveness of a burn rehabilitation workshop addressing confidence in therapy
      providers.
AB  - The study first assessed comfort levels of physical and occupational therapists
      who provide burn care prior to a hands-on intervention, then assessed therapists'
      confidence levels following an educational intervention. Physical and
      occupational therapists who previously treated burn survivors were invited to
      complete a preworkshop confidence level survey. From this information, four burn
      rehabilitation interventional categories were identified: positioning and
      exercise, compression, wound healing, and burn resources. A one-day workshop was
      held targeting these categories. Surveys were offered at the conclusion of the
      workshop as well as at 6-month follow-up. Initial survey results (n = 31)
      indicated that more than 75% of therapists felt unconfident or strongly
      unconfident in providing burn rehabilitation to patients. The postworkshop survey
      demonstrated significant improvements in all interventional categories. Further
      analysis revealed that baseline confidence levels for positioning and exercise
      were significantly higher than the other categories (P < .03). Six-month follow
      up results (n = 20) confirmed that confidence gained from the workshop remained
      significantly higher than preworkshop confidence levels. Baseline therapists'
      confidence levels in treating burn survivors were low, but improved following a
      one-day educational workshop. Providing hands-on burn education improved the
      confidence of therapists who treat burn survivors. Future efforts to improve
      therapist confidence and patient outcomes need to be explored.

PMID- 23128136
TI  - Destructive pulmonary effects of smoke inhalation and simultaneous alterations in
      circulating IL-6, TNF-alpha, and IFN-gamma levels at different burn depths: an
      experimental study on rats.
AB  - The current study sought to examine the interactions between inflammatory and
      immune events in the lung and circulating interleukin-6 (IL-6), tumor necrosis
      factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) levels at different
      burn depths with concomitant smoke inhalation in the rat model. Forty-eight
      female Sprague-Dawley rats were divided into six groups: S, sham; P, partial
      thickness burns; F, full-thickness burns; I, inhalation; Pi, partial-thickness
      burns + inhalation; and Fi, full-thickness burns + inhalation. Blood samples and
      lung biopsies were obtained 24 hours later. Blood levels of IL-6, TNF-alpha, and
      IF-gamma were measured with enzyme-linked immunosorbent assay. The proportions of
      CD3+ lymphocytes and CD68+ macrophages in the biopsies were studied
      immunohistochemically. The most severe inflammatory changes, except the
      neutrophil sequestration, were observed in the Fi group. A dense amount of
      neutrophils was observed in the F group. Edema and massive alveolar bleeding were
      seen in the I, Pi, and Fi groups. The amount of CD3+ lymphocytes were dense in
      the P, F, and Pi groups. The amount of CD68+ macrophages were significantly dense
      in Pi, F, I, and Fi groups. IL-6, TNF-alpha, and IF-gamma increased in all groups
      when compared to the S group. The highest IL-6 level was seen in the Fi group.
      TNF-alpha significantly increased in the F, Pi, I, and Fi groups. Increase in IFN
      gamma levels in the Pi and Fi groups was significantly higher than in the P and F
      groups. In concomitant smoke inhalation and skin burns, pulmonary damage and
      systemic inflammatory response are related and may be evaluated by blood levels
      of IL-6, TNF-alpha, and IFN-gamma cytokines.

PMID- 23128137
TI  - Burn victim: story of a survivor.

PMID- 23128138
TI  - Prophylaxis against Herpes Simplex Virus reactivation in patients with facial
      burns: a potential role for L-lysine.

PMID- 23128139
TI  - Novel surgical approach for axillary hidradenitis suppurativa using a bilayer
      dermal regeneration template:  a retrospective case study.
AB  - Hidradenitis suppurativa (HS) is a chronic debilitating disease of apocrine gland
      bearing skin characterized by recurrent abscesses with subsequent rupture,
      scarring, and draining sinus tracts, most frequently affecting the axillary,
      inguinal, and anogenital regions. Conservative and temporizing treatment methods
      have been used to treat mild to moderate disease, but wide local excision of
      affected tissue is necessary for advanced disease. This creates a large soft
      tissue defect for which there is no consensus for reconstruction. Recovery is
      hampered by disease recurrence, tissue necrosis, and reoperation. The authors
      have described in this case study an alternative surgical approach to treat
      severe HS. All surgical procedures were performed by dedicated burn surgeons at a
      regional burn center using a two-stage surgical approach. The first stage is a
      wide local excision of all affected axillary tissue with immediate placement of a
      bilayer dermal regeneration template to cover the defect. This is secured with a
      negative pressure wound therapy dressing. The second stage uses a thin split
      thickness skin graft to close the wound. Results of four patients are presented.
      There were no recurrences of HS. Two patients required reoperations to address
      granulation tissue overgrowth and small areas of autograft loss. One patient
      experienced skin substitute loss as a result of infection. Inadequate excision of
      HS is the leading cause of disease recurrence. Using a bilayer dermal
      regeneration template with subsequent skin graft, surgeons can be aggressive in
      their excision of HS, achieving satisfactory functional and cosmetic results and
      minimizing axillary recurrence.

PMID- 23128140
TI  - Microtubule-binding sites of the CH domain of EB1 and its autoinhibition revealed
      by NMR.
AB  - End-binding protein 1 (EB1) is one of the best studied plus-end tracking
      proteins. It is known that EB1 specifically binds the plus ends of microtubules
      (MTs) and promotes MT growth. EB1 activity is thought to be autoinhibited by an
      intramolecular interaction. Recent cryo-EM analyses showed that the CH domain of
      Mal3p (Schizosaccharomyces pombe EB1 homolog) binds to GMPCPP-MT (Sandblad, L.
      Cell 127 (2006) 1415-24), and strongly binds GTPgammaS-MT which is proposed to
      mimic MT plus ends better than GMPCPP-MT (Maurer S.P. et al. Cell 149 (2012) 371
      82). Here, we report on the MT binding sites of the CH domain of EB1 as revealed
      by NMR using the transferred cross-saturation method. In this study, we used
      GMPCPP-MT and found that the MT binding sites are very similar to the binding
      site for GTPgammaS-MT as suggested by cryo-EM (Maurer S.P. et al. Cell 149 (2012)
      371-82). Notably, the N-terminal tip of helix alpha6 of the CH domain did not
      make contact with GMPCPP-MT, in contrast to the cryo-EM study which showed that
      it is closely located to a putative switch region of beta-tubulin in GTPgammaS-MT
      (Maurer S.P. et al. Cell 149 (2012) 371-82). Further, we found that the
      intramolecular interaction site of EB1 overlaps the MT binding sites, indicating
      that the MT binding sites are masked by interaction with the C-terminal domain.
      We propose a structural view of autoinhibition and its release mechanism through
      competition binding with binding partners such as adenomatous polyposis coli
      protein.

PMID- 23128142
TI  - A zebrafish phenotypic assay for assessing drug-induced hepatotoxicity.
AB  - INTRODUCTION: Numerous studies have confirmed that zebrafish and mammalian
      toxicity profiles are strikingly similar and the transparency of larval zebrafish
      permits direct in vivo assessment of drug toxicity including hepatotoxicity in
      zebrafish. METHODS: Hepatotoxicity of 6 known mammalian hepatotoxic drugs
      (acetaminophen [APAP], aspirin, tetracycline HCl, sodium valproate,
      cyclophosphamide and erythromycin) and 2 non-hepatotoxic compounds (sucrose and
      biotin) were quantitatively assessed in larval zebrafish using three specific
      phenotypic endpoints of hepatotoxicity: liver degeneration, changes in liver size
      and yolk sac retention. Zebrafish liver degeneration was originally screened
      visually, quantified using an image-based morphometric analysis and confirmed by
      histopathology. RESULTS: All the tested mammalian hepatotoxic drugs induced liver
      degeneration, reduced liver size and delayed yolk sac absorption in larval
      zebrafish, whereas the non-hepatotoxic compounds did not have observable adverse
      effect on zebrafish liver. The overall prediction success rate for hepatotoxic
      drugs and non-hepatotoxic compounds in zebrafish was 100% (8/8) as compared with
      mammalian results, suggesting that hepatotoxic drugs in mammals also caused
      similar hepatotoxicity in zebrafish. DISCUSSION: Larval zebrafish phenotypic
      assay is a highly predictive animal model for rapidly in vivo assessment of
      compound hepatotoxicity. This convenient, reproducible animal model saves time
      and money for drug discovery and can serve as an intermediate step between cell
      based evaluation and conventional animal testing of hepatotoxicity.

PMID- 23128143
TI  - Shape-conserving enhancement of vibrational circular dichroism in lanthanide
      complexes.
AB  - The VCD spectra of lanthanide chelates with two chiral ligands display conserved
      sequences of bands throughout the Ln series. Some compounds (Tm, Yb) feature
      increased bands and strongly improved signal-to-noise ratios, an effect we dub
      Lanthanide Induced VCD Enhancement (LIVE).

PMID- 23128141
TI  - Collagen recognition and transmembrane signalling by discoidin domain receptors.
AB  - The discoidin domain receptors, DDR1 and DDR2, are two closely related receptor
      tyrosine kinases that are activated by triple-helical collagen in a slow and
      sustained manner. The DDRs have important roles in embryo development and their
      dysregulation is associated with human diseases, such as fibrosis, arthritis and
      cancer. The extracellular region of DDRs consists of a collagen-binding discoidin
      (DS) domain and a DS-like domain. The transmembrane region mediates the ligand
      independent dimerisation of DDRs and is connected to the tyrosine kinase domain
      by an unusually long juxtamembrane domain. The major DDR binding site in
      fibrillar collagens is a GVMGFO motif (O is hydroxyproline), which is recognised
      by an amphiphilic trench at the top of the DS domain. How collagen binding leads
      to DDR activation is not understood. GVMGFO-containing triple-helical peptides
      activate DDRs with the characteristic slow kinetics, suggesting that the
      supramolecular structure of collagen is not required. Activation can be blocked
      allosterically by monoclonal antibodies that bind to the DS-like domain. Thus,
      collagen most likely causes a conformational change within the DDR dimer, which
      may lead to the formation of larger DDR clusters. This article is part of a
      Special Issue entitled: Emerging recognition and activation mechanisms of
      receptor tyrosine kinases. 

PMID- 23128144
TI  - Tolerating increases in the serum creatinine following aggressive treatment of
      chronic kidney disease, hypertension and proteinuria: pre-renal success.
AB  - BACKGROUND: Blood pressure (BP) reduction in patients with chronic kidney disease
      (CKD), particularly with a renin-angiotensin system inhibitor (RASI), commonly
      leads to an initial decrease in glomerular filtration rate. The current clinical
      guideline, based on studies with single RASIs, is to tolerate an increase in the
      serum creatinine only up to 30%. This guideline has aptly guided CKD care for
      over a decade, but should be updated in the contemporary context of more
      aggressive RASI and diuretic use. METHODS: This study is a retrospective review
      of 48 mostly African-American patients with CKD treated with multiple and/or high
      dose renin-angiotensin system (RAS) inhibition and diuretics, targeting both low
      BP and reduction of urine protein. RASI was not reduced in response to initial
      increases in serum creatinine greater than 30%. RESULTS: A clinically well
      tolerated increase in serum creatinine over 30% during the first year occurred in
      41% of the patients. Treatment was unaltered, and target goals for BP and urine
      protein were typically achieved. After the point of maximal serum creatinine in
      the first year, these patients had minimal progression of disease over the next 6
      years, with a long-term estimated glomerular filtration rate slope of only -0.52
      ml/min/year/1.73 m(2). Only 25% progressed to end-stage renal disease or death.
      CONCLUSION: The 30% limitation to initial increases in the serum creatinine still
      pertains for single RASI at usual doses. However, favorable long-term outcomes
      suggest that initial increases over 30% should be tolerated in the context of
      dual goal-directed, more aggressive RASI and diuretic use.

PMID- 23128145
TI  - Solid-state, polymer-based fiber solar cells with carbon nanotube electrodes.
AB  - Most previous fiber-shaped solar cells were based on photoelectrochemical systems
      involving liquid electrolytes, which had issues such as device encapsulation and
      stability. Here, we deposited classical semiconducting polymer-based bulk
      heterojunction layers onto stainless steel wires to form primary electrodes and
      adopted carbon nanotube thin films or densified yarns to replace conventional
      metal counter electrodes. The polymer-based fiber cells with nanotube film or
      yarn electrodes showed power conversion efficiencies in the range 1.4% to 2.3%,
      with stable performance upon rotation and large-angle bending and during long
      time storage without further encapsulation. Our fiber solar cells consisting of a
      polymeric active layer sandwiched between steel and carbon electrodes have
      potential in the manufacturing of low-cost, liquid-free, and flexible fiber-based
      photovoltaics.

PMID- 23128146
TI  - Modelling fluorescence in clinical photodynamic therapy.
AB  - Understanding the interactions of non-ionizing radiation with living organisms
      has been the focus of much research over recent decades. The complex nature of
      these interactions warrants development of theoretical and experimental studies
      to gain an insight into predicting and monitoring the success of photodynamic
      therapy (PDT) protocols. There is a major impetus towards evidence-based
      recommendations for patient diagnosis, treatment and management. Knowledge of the
      biophysical aspects of PDT is important for improving dosimetry protocols.
      Fluorescence in clinical PDT may be used to detect and diagnose pre-malignant and
      malignant conditions, while photobleaching can monitor changes in fluorescence
      during treatment. Combining empirical fluorescence photobleaching clinical data
      with computational modelling enables clinical PDT dosimetry protocols to be
      investigated with a view to optimising treatment regimes. We will discuss how
      Monte Carlo radiation transfer (MCRT) modelling has been intercalated in the
      field of fluorescence detection and PDT. In this paper we highlight important
      aspects of basic research in PDT by reporting on the current utilisation of
      fluorescence in clinical PDT from both a clinical and theoretical perspective.
      Understanding and knowledge of light propagation in biological tissue from these
      perspectives should have a positive impact on treatment planning.

PMID- 23128148
TI  - Segmental left ventricular hypokinesis is associated with embolic signals in
      transcranial Doppler.
AB  - INTRODUCTION: Global left ventricular (LV) hypokinesis is considered to be the
      cause of stroke, while the significance of segmental wall motion abnormalities is
      still unknown. OBJECTIVES: The aim of the study was to determine the frequency of
      embolic signals in the middle cerebral artery in patients with segmental LV wall
      hypokinesis in the course of coronary artery disease (CAD) with and without
      stroke. PATIENTS AND METHODS: The study included 68 patients (aged 21-87 years)
      with segmental LV wall hypokinesis (33 patients without and 35 with stroke). The
      reference group comprised 30 patients (aged 43-76 years) with atherosclerotic
      risk factors; the control group comprised 37 healthy volunteers (aged 41-71
      years). All subjects underwent echocardiography and carotid and transcranial
      Doppler ultrasound with the detection of microembolic signals. RESULTS: Embolic
      signals were observed significantly more often in patients with segmental LV wall
      hypokinesis than in the control and reference groups. In patients with CAD and
      stroke, an increased number of embolic signals (>=3) was observed significantly
      more often compared with patients without stroke. Compared with other locations,
      interventricular septum and apex hypokinesis was associated with a higher
      frequency of embolic signals in the middle cerebral arteries. CONCLUSIONS:
      Segmental LV motion abnormalities in the form of hypokinesis in patients with CAD
      are associated with the presence of embolic signals in the middle cerebral
      arteries, which may have clinical significance as a risk factor for stroke.

PMID- 23128150
TI  - Molecular relationships and classification of several tufted capuchin lineages
      (Cebus apella, Cebus xanthosternos and Cebus nigritus, Cebidae), by means of
      mitochondrial cytochrome oxidase II gene sequences.
AB  - The morphological systematics of the tufted capuchins is confusing. In an attempt
      to clarify the complex systematics and phylogeography of this taxon, we provide a
      first molecular analysis. We obtained mitochondrial cytochrome oxidase II
      (mtCOII) gene sequences from 49 tufted capuchins that had exact geographic
      origins from diverse lineages in Colombia, Peru, Bolivia, French Guyana, Brazil,
      Argentina and Paraguay and that belonged to clearly recognized morphological
      taxa. This project had 4 main findings: (1) we determined 2 established and
      related taxa in the northern Amazon River area, which we named C. a. apella and
      C. a. fatuellus. C. a. apella is distributed from French Guyana until, at least,
      the Negro River in the northern Brazilian Amazon, whereas C. a. fatuellus is
      distributed throughout the Colombian Eastern Llanos and the northern Colombian
      Amazon. We also determined 2 other southern C. apella taxa, which we named C. a.
      macrodon and C. a. cay. C. a. macrodon has a western and southern Amazon
      distribution, while C. a. cay has a more southern distribution outside the Amazon
      basin. (2) In the upper Amazon basin, there is a unique lineage (C. a.
      macrocephalus) with 1 widely distributed haplotype. The 4 morphological
      subspecies (C. a. maranonis, C. a. macrocephalus, C. a. peruanus, C. a.
      pallidus), and maybe a fifth unknown subspecies, described in this area were
      molecularly undifferentiated at least for the mitochondrial gene analyzed. (3)
      Our molecular analysis determined that 1 individual of C. robustus fell into the
      lineage of C. a. macrocephalus. Therefore, this form does not receive any
      specific name. (4) The animals classified a priori as C. nigritus and C.
      xanthosternos (because of their morphological phenotypes and by their
      geographical origins) were clearly differentiated from the other specimens
      analyzed with the molecular marker employed. Therefore, we consider that these 2
      lineages could be assigned the status of full species following the biological
      species definition. (5) In 2001, Groves described 4 tufted capuchin species (C.
      apella, C. libidinosus, C. nigritus and C. xanthosternos), while Silva Jr.
      determined 7 species (C. apella, C. macrocephalus, C. libidinosus, C. cay, C.
      nigritus, C. robustus and C. xanthosternos). The tests of Swofford-Olsen-Waddell
      Hillis, of Shimodaira and Hasegawa and of Templeton did not fit with either of
      these two classificatory schemes, although Groves' scheme was better with regard
      to our data than that of Silva Jr. (6) All the temporal splits among the tufted
      capuchin taxa studied were estimated to have occurred during the last phase of
      the Pleistocene by using the rho statistic applied to the median joining
      haplotype network.

PMID- 23128152
TI  - Decision making in the pathway from genes to psychiatric and substance use
      disorders.
AB  - In influencing risk for psychiatric and substance use disorders, genes are
      typically conceptualized as working in silent physiological pathways in the
      bowels of our biology, far from the influences of human desires. I here argue
      that this model of gene action is too restricted. At the individual, family and
      societal level, humans can, through their decision-making capacity, intervene in
      causal pathways from genes to behavior. At the individual level, I present four
      paradigmatic cases involving alcohol dependence, major depression, general
      externalizing behaviors and animal phobia showing how human decisions can inhibit
      the expression of risk genes. I review the literatures demonstrating that
      parental behaviors can suppress or augment the heritability of traits in their
      children, and social attitudes can alter and even create causal pathways from
      genes to phenotypes. We evolved from organisms whose nervous systems were
      networks of reflexes that then developed simple cognitive systems and finally
      self-reflection. Just as our cognitions have gone 'meta,' we are now nearing a
      time when we can go 'meta' about our genetic risk. For many psychiatric
      disorders, our risk genes are not entirely cordoned off in our silent,
      purposeless biological substrate. Rather, we are able to make decisions that
      impact on the expression of our own genomes, those of our loved ones and those of
      our friends and neighbors. Our actions and our genes are often weaved together,
      integrated into the fabric of our lives.

PMID- 23128151
TI  - Fast-food and full-service restaurant consumption among children and adolescents:
      effect on energy, beverage, and nutrient intake.
AB  - OBJECTIVE: To examine the effect of fast-food and full-service restaurant
      consumption on total energy intake, dietary indicators, and beverage consumption.
      DESIGN: Individual-level fixed-effects estimation based on 2 nonconsecutive 24
      hour dietary recalls. SETTING: Nationally representative data from the 2003-2004,
      2005-2006, and 2007-2008 National Health and Nutrition Examination Survey.
      PARTICIPANTS: Children aged 2 to 11 years (n = 4717) and adolescents aged 12 to
      19 years (n = 4699). MAIN OUTCOME MEASURES: Daily total energy intake in
      kilocalories; intake of grams of sugar, total fat, saturated fat, and protein and
      milligrams of sodium; and total grams of sugar-sweetened beverages, regular soda,
      and milk consumed. RESULTS: Fast-food and full-service restaurant consumption,
      respectively, was associated with a net increase in daily total energy intake of
      126.29 kcal and 160.49 kcal for children and 309.53 kcal and 267.30 kcal for
      adolescents and with higher intake of regular soda (73.77 g and 88.28 g for
      children and 163.67 g and 107.25 g for adolescents) and sugar-sweetened beverages
      generally. Fast-food consumption increased intake of total fat (7.03-14.36 g),
      saturated fat (1.99-4.64 g), and sugar (5.71-16.24 g) for both age groups and
      sodium (396.28 mg) and protein (7.94 g) for adolescents. Full-service restaurant
      consumption was associated with increases in all nutrients examined. Additional
      key findings were (1) adverse effects on diet were larger for lower-income
      children and adolescents and (2) among adolescents, increased soda intake was
      twice as large when fast food was consumed away from home than at home.
      CONCLUSION: Fast-food and full-service restaurant consumption is associated with
      higher net total energy intake and poorer diet quality.

PMID- 23128153
TI  - State-dependent changes in hippocampal grey matter in depression.
AB  - Reduced hippocampal volume has been reported in depression and may be involved in
      the aetiology of depressive symptoms and vulnerability to depressive relapse.
      Neuroplasticity following antidepressant drug treatment in the hippocampus has
      been demonstrated in animal models but adaptive changes after such treatment have
      not been shown in humans. In this study, we determined whether grey matter loss
      in the hippocampus in depression (1) is present in medication-free depressed (2)
      changes in response to antidepressant treatment and (3) is present as a stable
      trait in medication-free remitted patients. Sixty-four medication-free unipolar
      depressed patients: 39 currently depressed and 25 in remission, and 66 healthy
      controls (HC) underwent structural magnetic resonance imaging in a cross
      sectional and longitudinal design. Thirty-two currently depressed participants
      were then treated with the antidepressant citalopram for 8 weeks. Adherence to
      treatment was evaluated by measuring plasma citalopram concentration. We measured
      regional variation in grey matter concentration by using voxel-based morphometry
      Diffeomorphic Anatomical Registration Through Exponentiated Lie algebra. Patients
      with current depression had bilaterally reduced grey matter in the hippocampus
      compared with HC and untreated patients in stable remission with the latter
      groups not differing. An increase in grey matter was observed in the hippocampus
      following treatment with citalopram in currently depressed patients. Grey matter
      reduction in the hippocampus appears specific to the depressed state and is a
      potential biomarker for a depressive episode. 

PMID- 23128155
TI  - Uremic plasma impairs barrier function and depletes the tight junction protein
      constituents of intestinal epithelium.
AB  - BACKGROUND: Chronic kidney disease (CKD) causes intestinal barrier dysfunction
      which by allowing influx of endotoxin and other noxious products contributes to
      the CKD-associated systemic inflammation and uremic toxicity. We have recently
      shown that intestinal barrier dysfunction in CKD animals is due to degradation of
      transcellular (claudin-1 and occludin) and intracellular (ZO1) constituents of
      epithelial tight junction (TJ). This study determined whether CKD-associated
      disruption of TJ is mediated by retained uremic toxins/metabolites and, if so,
      whether they are removed by hemodialysis. METHODS: The TJ-forming human
      enterocytes (T84 cells) were seeded on the Transwell plates and utilized when
      transepithelial electrical resistance (TER) exceeded 1,000 mOmega/cm(2) to ensure
      full polarization and TJ formation. The cells were then incubated for 24 h in
      media containing 10% pre- or posthemodialysis plasma from end-stage renal disease
      (ESRD) patients or healthy individuals. TER was then measured and cells were
      processed for Western blot and immunohistological analyses. RESULTS: Compared
      with the control plasma, incubation in media containing predialysis plasma from
      ESRD patients resulted in a marked drop in TER pointing to increased epithelial
      permeability. This was accompanied by significant reductions in claudin-1 (85%),
      occludin (15%), and ZO1 (70%) abundance. The severity of TJ damage and
      dysfunction was significantly less in cells exposed to the postdialysis in
      comparison to predialysis plasma. These findings point to the presence of as-yet
      unidentified product(s) in the uremic plasma capable of depleting epithelial TJ.
      CONCLUSIONS: Exposure to uremic milieu damages the intestinal epithelial TJ and
      impairs its barrier function, events which are mediated by agents which are
      partially removed by hemodialysis.

PMID- 23128154
TI  - Smoking quit success genotype score predicts quit success and distinct patterns
      of developmental involvement with common addictive substances.
AB  - Genotype scores that predict relevant clinical outcomes may detect other disease
      features and help direct prevention efforts. We report data that validate a
      previously established v1.0 smoking cessation quit success genotype score and
      describe striking differences in the score in individuals who display differing
      developmental trajectories of use of common addictive substances. In a cessation
      study, v1.0 genotype scores predicted ability to quit with P=0.00056 and area
      under receiver-operating characteristic curve 0.66. About 43% vs 13% quit in the
      upper vs lower genotype score terciles. Latent class growth analyses of a
      developmentally assessed sample identified three latent classes based on
      substance use. Higher v1.0 scores were associated with (a) higher probabilities
      of participant membership in a latent class that displayed low use of common
      addictive substances during adolescence (P=0.0004) and (b) lower probabilities of
      membership in a class that reported escalating use (P=0.001). These results
      indicate that: (a) we have identified genetic predictors of smoking cessation
      success, (b) genetic influences on quit success overlap with those that influence
      the rate at which addictive substance use is taken up during adolescence and (c)
      individuals at genetic risk for both escalating use of addictive substances and
      poor abilities to quit may provide especially urgent focus for prevention
      efforts. 

PMID- 23128156
TI  - Fluorinated methacrylamide chitosan hydrogel systems as adaptable oxygen carriers
      for wound healing.
AB  - In this study a series of novel, biocompatible hydrogels able to repeatedly
      takeup and deliver oxygen at beneficial levels have been developed by conjugating
      various perfluorocarbon (PFC) chains to methacrylamide chitosan via Schiff base
      nucleophilic substitution, followed by photopolymerization to form hydrogels. The
      synthesized fluorinated methacrylamide chitosan (MACF) hydrogels were confirmed
      by high resolution (19)F NMR. Synthesized MACF hydrogels were tested for their
      ability to takeup and then release oxygen for future use in dermal wound healing.
      Depending on the PFC substitution type maximum O(2) uptake was observed within 2
      6h, followed by complete release to the surrounding environment (5% CO(2)) within
      12-120h at oxygen partial pressures of 1-25mm Hg h(-1), providing outstanding
      system tuning for wound healing and regenerative medicine. MACFs with the most
      fluorines per substitution showed the greatest uptake and release of oxygen.
      Interestingly, adding PFC chains with a fluorinated aromatic group considerably
      enhanced oxygen uptake and extended release compared with a linear PFC chain with
      the same number of fluorine molecules. MACF hydrogels proved to be readily
      reloaded with oxygen once release was complete, and regeneration could be
      performed as long as the hydrogel was intact. Fibroblasts were cultured on MACFs
      and assays confirmed that materials containing more fluorines per substitution
      supported the most cells with the greatest metabolic activity. This result was
      true, even without oxygenation, suggesting PFC-facilitated oxygen diffusion from
      the culture medium. Finally, MACF gradient hydrogels were created, demonstrating
      that these materials can control oxygen levels on a spatial scale of millimeters
      and greatly enhance cellular proliferative and metabolic responses.

PMID- 23128157
TI  - Elucidation of adhesion-dependent spontaneous apoptosis in macrophages using
      phase separated PEG/polyurethane films.
AB  - Circulating monocytes undergo spontaneous apoptosis when there is no activation
      stimulus, which is critical to population control for proper host response to
      implants. As activation and apoptosis of monocytes/macrophages are regulated by
      cell-cell and cell-matrix interactions, their regulatory mechanism was
      investigated in this study using polyethylene glycol (PEG)-containing
      polyurethane films in which PEG-rich and polyester-rich domains were phase
      separated. Human blood monocyte-derived macrophages (HBMs) preferentially adhered
      to PEG domains (cell-matrix interaction) due to the low molecular weight (600 g
      mol-1), resulting in increased HBM density (cell-cell interaction). As both cell
      cell and cell-matrix interactions were promoted, HBM apoptosis increased, while
      their activation as measured by phagocytosis, intracellular reactive oxygen
      species (ROS) level and matrix metalloproteinase-9 production decreased compared
      to PEG-free films. When cell seeding density and cell-adhesive gelatin coating on
      silicone films were controlled, a cooperative role of cell-matrix (adhesion) and
      cell-cell (density) interactions in inducing HBM apoptosis was observed.
      Expression of the macrophage adhesion molecule CD11b caused apoptosis in this
      context, which was mediated by tissue necrosis factor-alpha signaling but down
      regulated by the ROS inhibitor diphenylene iodonium and the anti-inflammatory
      peptide Ac-SDKP, suggesting a new concept for the design of biomaterials that
      allows for cell adhesion without excessive inflammatory activation.

PMID- 23128158
TI  - A multilayered scaffold of a chitosan and gelatin hydrogel supported by a PCL
      core for cardiac tissue engineering.
AB  - A three-dimensional scaffold composed of self-assembled polycaprolactone (PCL)
      sandwiched in a gelatin-chitosan hydrogel was developed for use as a
      biodegradable patch with a potential for surgical reconstruction of congenital
      heart defects. The PCL core provides surgical handling, suturability and high
      initial tensile strength, while the gelatin-chitosan scaffold allows for cell
      attachment, with pore size and mechanical properties conducive to cardiomyocyte
      migration and function. The ultimate tensile stress of the PCL core, made from
      blends of 10, 46 and 80kDa (Mn) PCL, was controllable in the range of 2-4MPa,
      with lower average molecular weight PCL blends correlating with lower tensile
      stress. Blends with lower molecular weight PCL also had faster degradation
      (controllable from 0% to 7% weight loss in saline over 30 days) and larger pores.
      PCL scaffolds supporting a gelatin-chitosan emulsion gel showed no significant
      alteration in tensile stress, strain or tensile modulus. However, the compressive
      modulus of the composite tissue was similar to that of native tissue (~15kPa for
      50% gelatin and 50% chitosan). Electron microscopy revealed that the gelatin
      chitosan gel had a three-dimensional porous structure, with a mean pore diameter
      of ~80MUm, showed migration of neonatal rat ventricular myocytes (NRVM),
      maintained NRVM viability for over 7 days, and resulted in spontaneously beating
      scaffolds. This multi-layered scaffold has sufficient tensile strength and
      surgical handling for use as a cardiac patch, while allowing migration or pre
      loading of cardiac cells in a biomimetic environment to allow for eventual
      degradation of the patch and incorporation into native tissue.

PMID- 23128160
TI  - Experimental data confirm numerical modeling of the degradation process of
      magnesium alloys stents.
AB  - Biodegradable magnesium alloy stents (MAS) could present improved long-term
      clinical performances over commercial bare metal or drug-eluting stents. However,
      MAS were found to show limited mechanical support for diseased vessels due to
      fast degradation. Optimizing stent design through finite element analysis (FEA)
      is an efficient way to improve such properties. Following previous FEA works on
      design optimization and degradation modeling of MAS, this work carried out an
      experimental validation for the developed FEA model, thus proving its practical
      applicability of simulating MAS degradation. Twelve stent samples of AZ31B were
      manufactured according to two MAS designs (an optimized one and a conventional
      one), with six samples of each design. All the samples were balloon expanded and
      subsequently immersed in D-Hanks' solution for a degradation test lasting 14
      days. The experimental results showed that the samples of the optimized design
      had better corrosion resistance than those of the conventional design.
      Furthermore, the degradation process of the samples was dominated by uniform and
      stress corrosion. With the good match between the simulation and the experimental
      results, the work shows that the FEA numerical modeling constitutes an effective
      tool for design and thus the improvement of novel biodegradable MAS.

PMID- 23128159
TI  - Design of three-dimensional engineered protein hydrogels for tailored control of
      neurite growth.
AB  - The design of bioactive materials allows tailored studies probing cell
      biomaterial interactions, however, relatively few studies have examined the
      effects of ligand density and material stiffness on neurite growth in three
      dimensions. Elastin-like proteins (ELPs) have been designed with modular
      bioactive and structural regions to enable the systematic characterization of
      design parameters within three-dimensional (3-D) materials. To promote neurite
      out-growth and better understand the effects of common biomaterial design
      parameters on neuronal cultures we here focused on the cell-adhesive ligand
      density and hydrogel stiffness as design variables for ELP hydrogels. With the
      inherent design freedom of engineered proteins these 3-D ELP hydrogels enabled
      decoupled investigations into the effects of biomechanics and biochemistry on
      neurite out-growth from dorsal root ganglia. Increasing the cell-adhesive RGD
      ligand density from 0 to 1.9*10(7)ligands MUm(-3) led to a significant increase
      in the rate, length, and density of neurite out-growth, as quantified by a high
      throughput algorithm developed for dense neurite analysis. An approximately two
      fold improvement in total neurite out-growth was observed in materials with the
      higher ligand density at all time points up to 7 days. ELP hydrogels with initial
      elastic moduli of 0.5, 1.5, or 2.1kPa and identical RGD ligand densities revealed
      that the most compliant materials led to the greatest out-growth, with some
      neurites extending over 1800MUm by day 7. Given the ability of ELP hydrogels to
      efficiently promote neurite out-growth within defined and tunable 3-D
      microenvironments these materials may be useful in developing therapeutic nerve
      guides and the further study of basic neuron-biomaterial interactions.

PMID- 23128161
TI  - Surface properties and ion release from fluoride-containing bioactive glasses
      promote osteoblast differentiation and mineralization in vitro.
AB  - Bioactive glasses (BG) are suitable for bone regeneration applications as they
      bond with bone and can be tailored to release therapeutic ions. Fluoride, which
      is widely recognized to prevent dental caries, is efficacious in promoting bone
      formation and preventing osteoporosis-related fractures when administered at
      appropriate doses. To take advantage of these properties, we created BG
      incorporating increasing levels of fluoride whilst holding their silicate
      structure constant, and tested their effects on human osteoblasts in vitro. Our
      results demonstrate that, whilst cell proliferation was highest on low-fluoride
      containing BG, markers for differentiation and mineralization were highest on BG
      with the highest fluoride contents, a likely effect of a combination of surface
      effects and ion release. Furthermore, osteoblasts exposed to the dissolution
      products of fluoride-containing BG or early doses of sodium fluoride showed
      increased alkaline phosphatase activity, a marker for bone mineralization,
      suggesting that fluoride can direct osteoblast differentiation. Taken together,
      these results suggest that BG that can release therapeutic levels of fluoride may
      find use in a range of bone regeneration applications.

PMID- 23128162
TI  - TRPV4 channel activation improves the tensile properties of self-assembled
      articular cartilage constructs.
AB  - A persistent hurdle in the field of tissue regeneration is to produce tissues
      with biochemical and biomechanical properties robust enough to meet the
      aggressive physiological demands of the native milieu. In an effort to improve
      these properties tissues grown in vitro are often subjected to mechanical stimuli
      that aim to recapitulate the in vivo physiology. These mechanical stimuli are
      thought to produce downstream alterations in intracellular ion concentrations,
      which ultimately give rise to increased biosynthesis. There is mounting evidence
      that these perturbations in the cellular microenvironment are regulated by the
      Ca(2+)-permeable transient receptor potential vanilloid 4 (TRPV4) channel. In
      this study we examined the effects of targeted TRPV4 activation on self-assembled
      articular cartilage constructs. The objectives of this study were: (i) to
      determine whether TRPV4 activation would enhance self-assembled constructs; (ii)
      to identify an optimal treatment time window for TRPV4 activation; and (iii) to
      compare TRPV4 activation which Na(+)/K(+) pump inhibition, which has previously
      been shown to improve the construct tensile properties. This study employed a two
      phase approach. In Phase I self-assembled constructs were grown for 4weeks and
      subjected to treatment with the TRPV4 agonist 4alpha-phorbol-12,13-didecanoate
      (4alpha-PDD) during three treatment time windows: t=6-10, t=10-14, and t=14
      18days. Treatment for t=10-14days produced an 88% increase in collagen and a 153%
      increase in tensile stiffness. This treatment window was carried forward to Phase
      II. In Phase II we performed a head to head comparison between TRPV4 activation
      using 4alpha-PDD and Na(+)/K(+) pump inhibition using ouabain. Treatment with
      4alpha-PDD produced improvements on a par with ouabain (91-107% increases in
      tensile stiffness). The results of this study demonstrate the effectiveness of
      ion channel modulation as a strategy for improving engineered tissues. To our
      knowledge this is the first study to examine TRPV4 channel activation in tissue
      engineering.

PMID- 23128164
TI  - Human chorionic gonadotropin induces human macrophages to form intracytoplasmic
      vacuoles mimicking Hofbauer cells in human chorionic villi.
AB  - The most characteristic morphological feature of macrophages in the stroma of
      placental villi, known as Hofbauer cells, is their highly vacuolated appearance.
      They also show positive immunostaining for human chorionic gonadotropin (hCG) and
      express messenger ribonucleic acid of the luteinizing hormone/chorionic
      gonadotropin receptor with a deletion of exon 9 (LH/CG-R Delta9). Maternal hCG
      enters fetal plasma through the mesenchyme of the placental villi and promotes
      male sexual differentiation in early pregnancy; therefore, excess hCG may induce
      aberrant genital differentiation and hCG must be adjusted at the fetomaternal
      interface. We hypothesized that hCG is regulated by Hofbauer cells and that their
      peculiar vacuoles are involved in a cell-specific function. To assess the
      morphological modification and expression of LH/CG-R Delta9 in human macrophages
      after hCG exposure, the present study examined phorbol 12-myristate 13-acetate
      (PMA)-treated THP-1 cells, a human monocyte-macrophage cell line. hCG induced
      transient vacuole formation in PMA-treated THP-1 cells, morphologically mimicking
      Hofbauer cells. Immunocytochemistry showed that PMA-treated THP-1 cells
      incorporated hCG but not luteinizing hormone or follicle-stimulating hormone.
      Western blotting analyses demonstrated that PMA-treated THP-1 cells expressed an
      immunoreactive 60-kDa protein, designated as endogenous LH/CG-R Delta9. hCG
      induced a transient reduction in the LH/CG-R Delta9, which was synchronous with
      the appearance of cytoplasmic vacuoles. In conclusion, human macrophages
      regulating hCG via cytoplasmic LH/CG-R Delta9 mimic the morphological
      characteristics of Hofbauer cells. Their vacuoles may be associated with their
      cell-specific function to protect the fetus from exposure to excess maternal hCG
      during pregnancy.

PMID- 23128163
TI  - Effect of a monoclonal antibody to PCSK9 on low-density lipoprotein cholesterol
      levels in statin-intolerant patients: the GAUSS randomized trial.
AB  - CONTEXT: An estimated 10% to 20% of patients cannot tolerate statins or adequate
      doses to achieve treatment goals. Plasma proprotein convertase subtilisin/kexin
      type 9 (PCSK9) binds to low-density lipoprotein (LDL) receptors, promoting their
      degradation and increasing LDL cholesterol levels. In phase 1 studies, a human
      monoclonal antibody to PCSK9, AMG145, was well tolerated and reduced LDL
      cholesterol levels. OBJECTIVE: To assess the efficacy and tolerability of AMG145
      in patients with statin intolerance due to muscle-related side effects. DESIGN,
      SETTING, AND PATIENTS: A 12-week, randomized, double-blind, placebo- and
      ezetimibe-controlled, dose-ranging study conducted between July 2011 and May 2012
      in statin-intolerant adult patients at 33 international sites. INTERVENTION:
      Patients were randomized equally to 1 of 5 groups: AMG145 alone at doses of 280
      mg, 350 mg, or 420 mg; AMG145 at 420 mg plus 10 mg of ezetimibe; or 10 mg of
      ezetimibe plus placebo. AMG145 or placebo was administered subcutaneously every 4
      weeks. MAIN OUTCOME MEASURES: The primary end point was percentage change from
      baseline to week 12 in ultracentrifugation-measured LDL cholesterol. Other end
      points included measures of safety and tolerability of different doses of AMG145
      and AMG145 plus ezetimibe. RESULTS: Of 236 patients screened, 160 were randomized
      (mean age, 62 years; 64% female; mean baseline LDL cholesterol, 193 mg/dL); all
      patients had intolerance to 1 or more statins because of muscle-related events.
      At week 12, mean changes in LDL cholesterol levels were -67 mg/dL (-41%; 95% CI, 
      49% to -33%) for the AMG145, 280-mg, group; -70 mg/dL (-43%; 95% CI, -51% to 
      35%) for the 350-mg group; -91 mg/dL (-51%; 95% CI, -59% to -43%) for the 420-mg
      group; and -110 mg/dL (-63%; 95% CI, -71% to -55%) for the 420-mg/ezetimibe group
      compared with -14 mg/dL (-15%; 95% CI, -23% to -7.0%) for the placebo/ezetimibe
      group (P < .001). Four serious adverse events were reported with AMG145 (coronary
      artery disease, acute pancreatitis, hip fracture, syncope). Myalgia was the most
      common treatment-emergent adverse event during the study, occurring in 5 patients
      (15.6%) in the 280-mg group (n = 32); 1 patient (3.2%) in the 350-mg group (n =
      31), 1 patient (3.1%) in the 420-mg group (n = 32), 6 patients (20.0%) receiving
      420-mg AMG145/ezetimibe, and 1 patient (3.1%) receiving placebo/ezetimibe.
      CONCLUSION: In this phase 2 study in statin-intolerant patients, subcutaneous
      administration of a monoclonal antibody to PCSK9 significantly reduced LDL
      cholesterol levels and was associated with short-term tolerability. TRIAL
      REGISTRATION clinicaltrials.gov Identifier: NCT01375764.

PMID- 23128165
TI  - Neuropsychological patterns underlying anosognosia in people with cognitive
      impairment.
AB  - AIMS: To investigate, in a group of subjects with cognitive impairment, the
      relationship between anosognosia, in each dimension of insight, and
      neuropsychological domains. METHODS: Two hundred and seventy-one subjects
      affected by cognitive impairment were consecutively enrolled. Anosognosia was
      evaluated by means of the Clinical Insight Rating Scale (CIRS). The general level
      of cognitive impairment was evaluated by means of the Mini-Mental State
      Examination, while 8 cognitive domains were examined by means of
      neuropsychological tests. RESULTS: The number of subjects with anosognosia
      evaluated by means of the CIRS total score as well as those with anosognosia
      divided according to the reason for visit was higher in moderately cognitively
      impaired subjects than in mildly cognitively impaired subjects (p < 0.001). A
      relationship between anosognosia and neuropsychological scores was only found in
      mild cognitive impairment, with subjects with anosognosia displaying
      significantly lower Raven's Colored Progressive Matrices Test and Rey Auditory
      Verbal Learning Test-delayed recall scores than subjects without anosognosia.
      CONCLUSIONS: Our study suggests that the relationship between the severity of
      cognitive deficits and anosognosia in subjects with cognitive impairment is
      partial and depends on the specific domain of unawareness. Furthermore, in the
      early phase of cognitive impairment, the presence of specific cognitive deficits
      suggests that the nature of anosognosia is domain-specific.

PMID- 23128166
TI  - Early conditions in the breastfeeding of premature newborn infants.
AB  - PURPOSE: To describe the breastfeeding initial conditions for premature infants.
      METHODS: The sample consisted on 26 mother/baby dyads. The babies had an average
      of 36.1 weeks corrected gestational age and were hospitalized in a Neonatal
      Intensive Care Unit in Southern Brazil. Data was collected from medical records,
      and the observation of the dyads was conducted during feeding, using the
      Observation and Evaluation of the Breastfeeding Protocol. Favorable and
      unfavorable behaviors were registered regarding position, responses, suction,
      affection and anatomy of the breast. After the observation, a questionnaire was
      applied to the mothers. RESULTS: The best results refer to the position of
      mother/child and affection and the poorer ones to the infant responses.
      Statistically significant correlations by the Spearman Correlations Coefficient
      were observed between some items of the protocol and other study variables.
      CONCLUSION: Most premature infants from this sample presented a satisfactory
      initiation on analyzed aspects referring to breastfeeding. Still, we emphasize
      the need of practices for breastfeeding effectiveness and its encouragement in
      this population.

PMID- 23128168
TI  - Electromyographic and ultrasonographic characterization of masticatory function
      in individuals with normal occlusion.
AB  - PURPOSE: To characterize the motor control of the masseter and temporal muscles
      and the morphology of the masseter muscles during mastication in individuals with
      normal occlusion and to verify the consistency between surface electromyography
      (sEMG) and ultrasound (USD). METHODS: Participants were 22 adults, of both
      genders, with no alterations of the oral myofuntional system. The procedures
      performed included sEMG of the masseter (MM) and temporal (TM) muscles and USD of
      the MM, each during three tasks: resting condition and maximum voluntary dental
      clench with and without cotton rolls. RESULTS: The following statistical tests
      were used: Kolmogorov-Smirnov, paired t-test and Spearman correlation
      (significance level of 5%). The sEMG data indicated a significant difference
      between the MM and TM during the maximum voluntary clench with and without cotton
      rolls, and the TM was more active than the TM in both clenching tasks. No
      significant difference was observed between the sides of the face when assessed
      with sEMG or USD. A significant positive correlation between the exams was
      observed for the left maximum voluntary dental clench with and without cotton
      rolls, and a trend toward significance was found for the right maximum dental
      clench without cotton rolls. CONCLUSION: The comparison of sEMG to USD for the
      investigation of muscle function reveals important information about the
      physiology of skeletal muscles. The results of the present study suggest a
      correlation between sEMG and USD, i.e., between increased electrical activity and
      the corresponding increase in muscle thickness.

PMID- 23128167
TI  - Analysis of the association among types of breastfeeding, presence of child
      development risk, socioeconomic and obstetric variables.
AB  - PURPOSE: To investigate the association among types of breastfeeding, presence of
      child development risk, socioeconomic and obstetric variables. METHODS: The
      sample was composed of 182 mother-child dyades. Data were collected through an
      initial interview about breastfeeding; obstetric, socioeconomic, demographic and
      psychosocial aspects; and mother-child interaction analysis by the Child
      Development Risk Inventory. The data were organized in categories related to
      breastfeeding, presence or absence of child development risk, obstetric and
      socioeconomic variables, and were analyzed in Statistica 9.0 software for
      statistical analysis. RESULTS: The mixed breastfeeding type shows statistical
      correlation between presence of child development risk as well as to variables
      such as prematurity, low weight, birth intercurrences and mother's domestic
      profession. CONCLUSION: The results show that factors such as low weight,
      prematurity and presence of birth intercurrences can be associated to mixed
      breastfeeding, even if the mothers present physical and time availability for
      breastfeeding. These variables can be associated to mother-child initial
      interactions detected by Child Development Risk Inventory.

PMID- 23128169
TI  - Components of the acoustic swallowing signal: preliminary study.
AB  - PURPOSE: To analyze the components of the acoustic signal of swallowing using a
      specific software. METHODS: Fourteen healthy subjects ranging in age from 20 to
      50 years (mean age 31 +/- 10 years), were evaluated. Data collection consisted on
      the simultaneous capture of the swallowing audio with a microphone and of the
      swallowing videofluoroscopic image. The bursts of the swallowing acoustic signal
      were identified and their duration and the interval between them were later
      analyzed using a specific software, which allowed the simultaneous analyses
      between the acoustic wave and the videofluoroscopic image. RESULTS: Three burst
      components were identified in most of the swallows evaluated. The first burst
      presented mean time of 87.3 milliseconds (ms) for water and 78.2 for the
      substance. The second burst presented mean time of 112.9 ms for water and 85.5
      for the pasty substance. The mean interval between first and second burst was
      82.1 ms for water and 95.3 ms for the pasty consistency, and between second and
      third burst was 339.8 ms for water and 322.0 ms for the pasty consistency.
      CONCLUSION: The software allowed the visualization of three bursts during the
      swallowing of healthy individuals, and showed that the swallowing signal in
      normal subjects is highly variable.

PMID- 23128170
TI  - Quality of life in swallowing in healthy elderly.
AB  - PURPOSE: To understand the self-perception of healthy elderly regarding possible
      swallowing difficulties. METHODS: Participants were 104 seniors, 62 women and 42
      men, ranging in age from 60 to 88 years (mean 70.6), who reported good general
      health, no history of degenerative diseases, neurological or any other diseases
      that could influence swallowing participated. All subjects underwent cognitive
      and emotional screening and presented satisfactory conditions for both. A
      questionnaire to gather general and health information, and the protocol SWAL-QOL
      were applied. The data were statistically analyzed. RESULTS: Most domains of the
      SWAL-QOL showed mean numbers close to the maximum score (100 points), indicating
      a positive perception of the elderly about quality of life related to swallowing.
      Individuals with dentures showed better rates in most domains when compared to
      non-users. Individuals who self-reported ill-fitting dentures had lower scores
      for the domains "burden", "eating duration" and "frequency of symptoms". Men and
      women differed only in the domains "sleep" and "fatigue", for which women had
      lower mean scores. There was no correlation between the SWAL-QOL scores obtained
      and the variables age and monthly income. CONCLUSION: Healthy elderly, in
      general, do not self-report significant changes in the quality of life related to
      swallowing. Moreover, there is no reduction of quality of life related to
      swallowing as age advances. Well-adjusted dentures minimize impairment related to
      swallowing.

PMID- 23128171
TI  - Noise perception in the workplace and auditory and extra-auditory symptoms
      referred by university professors.
AB  - PURPOSE: To investigate the correlation between noise in the work environment and
      auditory and extra-auditory symptoms referred by university professors. METHODS:
      Eighty five professors answered a questionnaire about identification, functional
      status, and health. The relationship between occupational noise and auditory and
      extra-auditory symptoms was investigated. Statistical analysis considered the
      significance level of 5%. RESULTS: None of the professors indicated absence of
      noise. Responses were grouped in Always (A) (n=21) and Not Always (NA) (n=63).
      Significant sources of noise were both the yard and another class, which were
      classified as high intensity; poor acoustic and echo. There was no association
      between referred noise and health complaints, such as digestive, hormonal,
      osteoarticular, dental, circulatory, respiratory and emotional complaints. There
      was also no association between referred noise and hearing complaints, and the
      group A showed higher occurrence of responses regarding noise nuisance, hearing
      difficulty and dizziness/vertigo, tinnitus, and earache. There was association
      between referred noise and voice alterations, and the group NA presented higher
      percentage of cases with voice alterations than the group A. CONCLUSION: The
      university environment was considered noisy; however, there was no association
      with auditory and extra-auditory symptoms. The hearing complaints were more
      evident among professors in the group A. Professors' health is a multi
      dimensional product and, therefore, noise cannot be considered the only
      aggravation factor.

PMID- 23128172
TI  - Interference of the linguistic variant in the repair strategies used during the
      phonological acquisition process.
AB  - PURPOSE: To investigate and compare the use of repair strategies in the
      acquisition of /R/ in simple onset, produced by children with typical
      phonological acquisition. METHODS: Speech data containing the /R/ from 120
      children with typical phonological acquisition (60 male and 60 female) from Santa
      Maria (RS) and Crissiumal (RS), Brazil, aged between 1 year and 6 months and 4
      years were used. To analyze the repair strategies, the following dependent
      variables were considered: omission, semivocalization, and liquid substitution;
      as well as the following independent variables: gender, age, precedent and
      following context, grammatical class, tonicity, number of syllables, and position
      in the word. The VARBRUL program was used for statistical analysis. RESULTS: The
      statistical program selected as significant for omission in Santa Maria the
      variables tonicity and gender, and in Crissiumal, tonicity and age. For
      semivocalization in Santa Maria, the program selected the variable gender, and in
      Crissiumal, tonicity. For lateral liquid substitution in Santa Maria the
      statistical program did not select any variable. However, in Crissiumal, the
      variables position in the word, gender, and age were selected. CONCLUSION: It was
      possible to observe that the repair strategies can diverge according to the
      dialect being used. Hence, it is important to consider the dialectal variation to
      make the phonological therapy more effective.

PMID- 23128173
TI  - Phonological acquisition of Brazilian Portuguese in children from Rio de Janeiro.
AB  - PURPOSE: To describe the typical course of phonological acquisition in Brazilian
      Portuguese, in view of clinical usage. METHODS: A picture naming test was used to
      collect speech samples from 480 children (240 female and 240 male) enrolled in
      public and private schools in the city of Rio de Janeiro, who were divided into
      five age groups between 3 and 8 years. Three types of analyses were conducted,
      and results were compared for age, gender, and socio-economic level: (1)
      phonological inventory analysis looking at how many and which consonants were
      acquired, (2) assessment of the percentage of consonants correct, and (3)
      phonological processes analysis. RESULTS: Results clearly indicate a faster
      acquisition in children of higher socio-economic level than in children of lower
      socio-economic level. Data also indicated that age is the most important factor
      in phonological acquisition. The completeness of the consonant inventory, the
      percentage of consonants correct, and the use of phonological processes improved
      with increasing age, and variability among children decreased. Gender
      differences, however, were not observed. CONCLUSION: The information collected
      may ultimately help speech-language pathologists in the assessment and treatment
      of children with speech sound disorders.

PMID- 23128174
TI  - Phonetic description of alveolar phones using electropalatography.
AB  - PURPOSE: To describe the articulation of the Brazilian Portuguese, by examining
      the tongue-palate contact in the production of consonantal phones. METHODS: The
      electropalatography (EPG) of the alveolar consonants of the Brazilian Portuguese
      produced by an individual with typical speech was used, considering the alveolar,
      post-alveolar, palatal, and velar rates, as well as the percentage of activated
      contacts at the point of maximum constriction, and the visual inspection of
      palatograms. RESULTS: As expected, it was observed that all the examined phones
      have more contact in the alveolar region at the point of maximum constriction.
      The phones /t/, /d/ and /n/ showed more alveolar contact, with total obstruction
      of the air stream; the fricative phones /s/ and /z/ were characterized by the
      absence of contact at the central longitudinal axis; the lateral phone /l/ did
      not present contact at the lateral longitudinal axis, and the tap /[symbol: see
      text]/ showed not only few tongue-palate contacts but it was also produced in the
      shortest duration time. CONCLUSION: The electopalatography allowed a detailed
      description of the extension of the tongue-palate contact in the different
      alveolar phones of the Brazilian Portuguese and how they occur.

PMID- 23128175
TI  - A concreteness judgment of words.
AB  - PURPOSE: To describe the judgement of the concreteness of a set of 162 Brazilian
      Portuguese words, prior to the elaboration of a speech recognition test, as well
      as to verify the influence of variables such as the frequency of occurrence of
      the words and age and undergraduate program year of the participants on the
      concreteness ratings. METHODS: Fifty undergraduate Speech-Language Pathology and
      Audiology students from a public university rated the concreteness of a set of
      162 words using a seven-point scale where the lowest concreteness degree was
      represented by number one and the highest by number seven. Participants were free
      to choose any number in the scale. RESULTS: The results showed a tri-modal
      distribution of values, suggesting the classification of three categories,
      according to the concreteness rating. The low concreteness category ranged from
      1.76 to 3.45; the medium concreteness category, from 3.46 to 4.95; and the high
      concreteness rating, from 4.96 to 6.70. Positive correlation was found between
      the concreteness rating and the coefficient of variation, whereby the higher the
      rating attributed to a word, the lesser variation in the responses. No
      significant correlation was found between concreteness ratings and the frequency
      of occurrence of words. The influence of age and undergraduate year was
      significant for some correlations. CONCLUSION: Results showed three concreteness
      categories, and suggest that concreteness can be considered an independent
      attribute of words, since their frequency of occurrence, as well as participants'
      age and undergraduate program year did not influence the ratings attributed. The
      words classified in the high concreteness category were subsequently used for the
      elaboration of a speech recognition test.

PMID- 23128176
TI  - Vocabulary, phonological awareness and rapid naming: contributions for spelling
      and written production.
AB  - PURPOSE: To investigate if the performance on linguistic tasks would be
      predictive of orthographic domain and quality of written productions. METHODS:
      Participants were 82 fourth graders of Elementary Education, from public and
      private schools of Sao Paulo, with ages ranging from 9 years to 10 years and 2
      months. The test battery was composed of an expressive vocabulary test,
      phonological awareness and rapid serial naming tasks, words and pseudowords
      spelling, and written text composition using a visual stimulus as a starting
      point. The statistical analysis included Spearman (r) correlations among all
      tasks. RESULTS: The results indicated that the better the vocabulary skills, the
      smaller the number of spelling errors and the better the quality of the written
      text productions, considering all the analyzed categories. Also, the higher
      performance in both phonological awareness and rapid object naming tasks was
      correlated to fewer spelling errors and written text productions with greater
      grammatical structure. CONCLUSION: The linguistic abilities analyzed in this
      study were predictive of subjects' spelling performance. The vocabulary skills
      were predictive of the quality of written text productions. However, phonological
      awareness and rapid serial naming were only predictive of children's performance
      concerning the syntactic and grammatical structure of their written text
      productions.

PMID- 23128177
TI  - Study on pragmatic assessment data reliability in children with typical language
      development.
AB  - The aim of this study was to verify the moment with more reliable data to survey
      children's pragmatic profile. Participants were five children with typical
      language development and ages between 7 years and 1 month and 8 years and 11
      months. Data collection involved a 150-minute recording of a child-researcher
      interaction, divided into five 30-minute individual sessions. Data were later
      analyzed according to a verbal communicative abilities protocol, and the
      individual pragmatic profiles of each 30-minute sample and the whole 150-minute
      sample were outlined for comparison (sessions 1 through 5 x overall total of
      sessions) of reliability indexes (RI) and reliability status (RS). Inter and
      intra-observer analyses were performed to calculate the RI and RS, respectively.
      The results presented by children 1 and 2 reached the larger RI in session 2; the
      child 3 showed similar RI values in sessions 3, 4 and 5; the child 4 had the
      largest RI in sessions 1 and 3; and the child 5 reached the same RI value in all
      sessions. Regarding the RS, session 2 presented the largest percentage of high
      reliability for most children, followed by session 3. On the analysis performed
      by category of verbal communicative abilities, session 3 presented the largest RS
      for dialogic and narrative-discursive abilities, and also for the overall total
      of verbal communicative abilities. In general, it was observed that sessions 2
      and 3 allowed the largest RI and RS on the analysis performed to outline the
      children's pragmatic profile.

PMID- 23128178
TI  - Phonological changes after the application of therapy approach based on
      distinctive features in the treatment of phonological disorder.
AB  - This study aimed to compare the phonological changes due to the application of a
      speech therapy approach based on distinctive features, using two types of target
      sounds (the ones which emphasize the contrast, and others which reinforce the
      distinctive features) in the treatment of phonological disorder. The sample was
      constituted by seven children with phonological disorder (four boys and three
      girls), with ages between 3 years and 10 months and 6 years and 9 months. The
      children were classified according to the severity of the phonological disorder
      and then underwent treatment based on the Modified Maximal Oppositions Model. Two
      subjects were grouped for each degree; one subject was treated by "contrast" and
      the other one by "reinforcement" of the distinctive features in which they showed
      difficulties. The moderate-severe degree was the only one to include only one
      subject. After 20 therapy sessions, the phonological changes before and after the
      treatment were analyzed, considering the type of stimulus presented ("contrast"
      or "reinforcement"). All subjects, either treated by "contrast" or
      "reinforcement", showed an increase in their Percentage of Consonants Correct
      (PCC), in the number of acquired sounds and of generalizations in their
      phonological inventories. It was verified that both groups presented changes in
      their phonological inventories. On the comparative analysis between the groups,
      it was observed that both groups, treated by "contrast" and by "reinforcement",
      demonstrated differences regarding the types of generalizations studied.

PMID- 23128179
TI  - Voice disorders in teachers: critical review on the worker's health surveillance
      practice.
AB  - PURPOSE: To analyze scientific bibliographic production on the practice of
      occupational health surveillance related to voice disorders in teachers. SEARCH
      STRATEGY: The Cochrane Handbook precepts which involves the formulation of the
      question to be investigated, the location, the studies selection and articles'
      critical evaluation were followed. SELECTION CRITERIA: The articles published
      between 2000 and 2011 were selected in the PubMed, LILACS, MEDLINE database, and
      the Cochrane Library using the descriptors voice disorders; teachers,
      occupational health, workers' health surveillance. DATA ANALYSIS: Texts were
      analyzed, using a standardized form when the following data were collected:
      objectives, research design, characteristics of the study group, obtained results
      and discussion on the practice of surveillance related to voice disorder.
      RESULTS: Initially, 141 studies were identified. After reviewing the titles and
      abstracts, considering inclusion and exclusion criteria, verifying consistency
      with the topic researched and eliminating the ones which were concurrently in
      more than one database, 32 articles were effectively analyzed for relating in the
      findings and/or conclusions to the practice of surveillance related to voice
      disorders in teachers. CONCLUSION: The practice of monitoring workers' health was
      evidenced in this research mainly as the identification of risk factors
      associated with voice disorders in teachers, aimed at the transformation of the
      working conditions and the assurance of quality of assistance to these workers as
      professionals.

PMID- 23128180
TI  - Influence of complaints and singing style in singers voice handicap.
AB  - The aim of this research was to verify whether the difference of singing styles
      and the presence of vocal complaints influence the perception of voice handicap
      of singers. One hundred eighteen singing voice handicap self-assessment protocols
      were selected: 17 popular singers with vocal complaints, 42 popular singers
      without complaints, 17 classic singers with complaints, and 42 classic singers
      without complaints. The groups were similar regarding age, gender and voice
      types. Both protocols used--Modern Singing Handicap Index (MSHI) and Classical
      Singing Handicap Index (CSHI)--have specific questions to their respective
      singing styles, and consist of 30 items equally divided into three subscales:
      disability (functional domain), handicap (emotional domain) and impairment
      (organic domain), answered according to the frequency of occurrence. Each
      subscale has a maximum of 40 points, and the total score is 120 points. The
      higher the score, the higher the singing voice handicap perceived. For
      statistical analysis, we used the ANOVA test, with 5% of significance. Classical
      and popular singers referred higher impairment, followed by disability and
      handicap. However, the degree of this perception varied according to the singing
      style and the presence of vocal complaints. The classical singers with vocal
      complaints showed higher voice handicap than popular singers with vocal
      complaints, while the classic singers without complaints reported lower handicap
      than popular singers without complaints. This evidences that classical singers
      have higher perception of their own voice, and that vocal disturbances in this
      group may cause greater voice handicap when compared to popular singers.

PMID- 23128181
TI  - This issue will provide a good update for speech-language pathologists and
      audiologists who seek for excellence on clinical care.

PMID- 23128182
TI  - Scientific methodology and teaching in Speech-Language Pathology and Audiology.

PMID- 23128184
TI  - Heterogeneous integration of InGaAs nanowires on the rear surface of Si solar
      cells for efficiency enhancement.
AB  - We demonstrate energy-conversion-efficiency (eta) enhancement of silicon (Si)
      solar cells by the heterogeneous integration of an In(x)Ga(1-x)As nanowire (NW)
      array on the rear surface. The NWs are grown via a catalyst-free, self-assembled
      method on Si(111) substrates using metalorganic chemical vapor deposition
      (MOCVD). Heavily p-doped In(x)Ga(1-x)As (x ~ 0.7) NW arrays are utilized as not
      only back-reflectors but also low bandgap rear-point-contacts of the Si solar
      cells. External quantum efficiency of the hybrid In(x)Ga(1-x)As NW-Si solar cell
      is increased over the entire solar response wavelength range; and eta is enhanced
      by 36% in comparison to Si solar cells processed under the same condition without
      the NWs.

PMID- 23128185
TI  - Heparinized magnetic mesoporous silica nanoparticles as multifunctional growth
      factor delivery carriers.
AB  - Well-defined magnetic mesoporous silica nanoparticles (MMSNs) with a core/shell
      structure were prepared via a one pot synthesis. Sphere-like magnetite aggregates
      were obtained as cores of the final nanoparticles by assembly in the presence of
      polyvinyl pyrrolidone and cetyltrimethylammonium bromide. The nanoparticles have
      the property of superparamagnetism with a saturation magnetization value of 20.3
      emu g(-1). In addition, the combination of heparin and fluorescence-labeled MMSNs
      endows the resultant particles (denoted as MFMSNs-HP) with magnetism and
      fluorescence properties, excellent dispersity in the buffer solutions and cell
      culture media, anticoagulant activity in the blood stream, and the controlled
      release of basic fibroblast growth factor (bFGF). Furthermore, the bFGF cell
      viability assays indicate that MFMSNs-HP has nearly no toxicity to human
      umbilical vein endothelial cells (HUVEC) up to a concentration of 200 MUg ml(-1),
      and the proliferation activity of bFGF incorporated into MFMSNs-HP could be
      retained for at least 6 days. All of these suggest that MFMSNs-HP may serve as a
      multifunctional carrier for the delivery of growth factors.

PMID- 23128183
TI  - Direct comparison of fixed flexion, radiography and MRI in knee osteoarthritis:
      responsiveness data from the Osteoarthritis Initiative.
AB  - OBJECTIVE: Minimum radiographic joint space width (mJSW) represents the Food and
      Drug Administration (FDA) standard for demonstrating structural therapeutic
      benefits for knee osteoarthritis (KOA), but only shows moderate responsiveness
      (sensitivity to change). We directly compare the responsiveness of magnetic
      resonance imaging (MRI)-based cartilage thickness and JSW measures from fixed
      flexion radiography (FFR) and explore the correlation of region-matched changes
      between both methods. METHODS: Nine hundred and sixty-seven knees of
      Osteoarthritis Initiative participants with radiographic KOA were studied: 445
      over 1 year with coronal FLASH MRI and FFR, and 375/522 over 1/2 years with
      sagittal DESS MRI and FFR. Standardized response means (SRM) of cartilage
      thickness and mJSW were compared using the sign-test. RESULTS: With FLASH MRI,
      SRM was -0.28 for medial femorotibial compartment (MFTC) cartilage loss vs -0.15
      for mJSW, and -0.32 vs -0.22 for the most sensitive MRI subregion (central MFTC)
      vs the most sensitive fixed-location JSW(x = 0.25). With DESS MRI, 1-year SRM was
      -0.34 for MFTC vs -0.22 for mJSW and -0.44 vs -0.28 for central MFTC vs JSW(x =
      0.225). Over 2 years, the SRM was significantly greater for MFTC than for mJSW (
      0.43 vs -0.31, P = 0.017) and for central MFTC than for JSW(x = 0.225) (-0.51 vs 
      0.44, P < 0.001). Correlations between changes in spatially matched MRI
      subregions and fixed-location JSW were not consistently higher (r = 0.10-0.51)
      than those between non-matched locations (r = 0.15-0.50). CONCLUSIONS: MRI
      displays greater responsiveness in KOA than JSW FFR-based JSW, with the greatest
      SRM observed in the central medial femorotibial compartment. Fixed-location
      radiographic measures appear not capable of determining the spatial distribution
      of femorotibial cartilage loss.

PMID- 23128186
TI  - Multimodality treatment of gynecomastia in patients receiving antiandrogen
      therapy for prostate cancer in the era of abiraterone acetate and new
      antiandrogen molecules.
AB  - Gynecomastia is a pathological enlargement of male breasts due to hormonal
      imbalance and elevation of estrogens at the expense of testosterone. It is very
      important to diagnose this disease precociously because it can be the expression
      of different underlying pathologies. Besides genetic, chromosomal or chronic
      diseases, drugs often represent the principal cause of this hormonal
      disequilibrium. In the elderly population, antiandrogen therapy for prostate
      cancer frequently induces gynecomastia, thus negatively affecting the patients'
      compliance to treatment because of physical and psychological discomfort deriving
      from this condition; gynecomastia can in fact be associated with severe breast
      pain, and it can modify how patients see their own body. During the past decades
      and even today, many different surgical, radiotherapeutic or clinical approaches
      have been proposed to prevent or treat this hypertrophy. This article focuses on
      gynecomastia associated with antiandrogen-based hormonal treatment and shortly
      reviews the currently most often used therapeutic options for preventing and
      treating this pathology.

PMID- 23128188
TI  - How women scientists fare in the Arab world.

PMID- 23128187
TI  - A one-pot multicomponent strategy for stereospecific construction of tricyclic
      pyrrolo[1,2-a]quinolines.
AB  - A novel multicomponent strategy for the efficient synthesis of tricyclic
      pyrrolo[1,2-a]quinolines has been described. The bond-forming efficiency,
      accessibility and generality of this synthesis make it highly attractive to
      assemble tri-heterocyclic scaffolds.

PMID- 23128201
TI  - Sahara solar plan loses its shine.

PMID- 23128200
TI  - L'Aquila verdict row grows.

PMID- 23128203
TI  - Theorists bridge space-time rips.

PMID- 23128202
TI  - NIH faces chimp housing quandary.

PMID- 23128204
TI  - Hepatitis E vaccine debuts.

PMID- 23128205
TI  - Bid to curb fried-food chemical goes cold.

PMID- 23128207
TI  - Science in the developing world: Eritrea's shattered science.

PMID- 23128208
TI  - Genomics: The single life.

PMID- 23128209
TI  - Model organisms: There's more to life than rats and flies.

PMID- 23128210
TI  - Genetic tests: Politics and fetal diagnostics collide.

PMID- 23128211
TI  - Policy: Base sustainable development goals on science.

PMID- 23128217
TI  - Nomenclature: Call to register new species in ZooBank.

PMID- 23128216
TI  - Structural genomics: Open collaboration is key to new drugs.

PMID- 23128218
TI  - Publishing: Handful of papers dominates citation.

PMID- 23128219
TI  - Conservation: Problems enforcing Ecuador ecology law.

PMID- 23128220
TI  - Materials science: Self-assembly gets new direction.

PMID- 23128222
TI  - Asteroids: Dark and stormy weather.

PMID- 23128224
TI  - Optics: Nanotube holograms.

PMID- 23128223
TI  - Neuroscience: Sleep to oblivion.

PMID- 23128225
TI  - Colloids with valence and specific directional bonding.
AB  - The ability to design and assemble three-dimensional structures from colloidal
      particles is limited by the absence of specific directional bonds. As a result,
      complex or low-coordination structures, common in atomic and molecular systems,
      are rare in the colloidal domain. Here we demonstrate a general method for
      creating the colloidal analogues of atoms with valence: colloidal particles with
      chemically distinct surface patches that imitate hybridized atomic orbitals,
      including sp, sp(2), sp(3), sp(3)d, sp(3)d(2) and sp(3)d(3). Functionalized with
      DNA with single-stranded sticky ends, patches on different particles can form
      highly directional bonds through programmable, specific and reversible DNA
      hybridization. These features allow the particles to self-assemble into
      'colloidal molecules' with triangular, tetrahedral and other bonding symmetries,
      and should also give access to a rich variety of new microstructured colloidal
      materials.

PMID- 23128227
TI  - Distinctive space weathering on Vesta from regolith mixing processes.
AB  - The surface of the asteroid Vesta has prominent near-infrared absorption bands
      characteristic of a range of pyroxenes, confirming a direct link to the basaltic
      howardite-eucrite-diogenite class of meteorites. Processes active in the space
      environment produce 'space weathering' products that substantially weaken or mask
      such diagnostic absorption on airless bodies observed elsewhere, and it has long
      been a mystery why Vesta's absorption bands are so strong. Analyses of soil
      samples from both the Moon and the asteroid Itokawa determined that nanophase
      metallic particles (commonly nanophase iron) accumulate on the rims of regolith
      grains with time, accounting for an observed optical degradation. These nanophase
      particles, believed to be related to solar wind and micrometeoroid bombardment
      processes, leave unique spectroscopic signatures that can be measured remotely
      but require sufficient spatial resolution to discern the geologic context and
      history of the surface, which has not been achieved for Vesta until now. Here we
      report that Vesta shows its own form of space weathering, which is quite
      different from that of other airless bodies visited. No evidence is detected on
      Vesta for accumulation of lunar-like nanophase iron on regolith particles, even
      though distinct material exposed at several fresh craters becomes gradually
      masked and fades into the background as the craters age. Instead, spectroscopic
      data reveal that on Vesta a locally homogenized upper regolith is generated with
      time through small-scale mixing of diverse surface components.

PMID- 23128228
TI  - Dark material on Vesta from the infall of carbonaceous volatile-rich material.
AB  - Localized dark and bright materials, often with extremely different albedos, were
      recently found on Vesta's surface. The range of albedos is among the largest
      observed on Solar System rocky bodies. These dark materials, often associated
      with craters, appear in ejecta and crater walls, and their pyroxene absorption
      strengths are correlated with material brightness. It was tentatively suggested
      that the dark material on Vesta could be either exogenic, from carbon-rich, low
      velocity impactors, or endogenic, from freshly exposed mafic material or impact
      melt, created or exposed by impacts. Here we report Vesta spectra and images and
      use them to derive and interpret the properties of the 'pure' dark and bright
      materials. We argue that the dark material is mainly from infall of hydrated
      carbonaceous material (like that found in a major class of meteorites and some
      comet surfaces), whereas the bright material is the uncontaminated indigenous
      Vesta basaltic soil. Dark material from low-albedo impactors is diffused over
      time through the Vestan regolith by impact mixing, creating broader, diffuse
      darker regions and finally Vesta's background surface material. This is
      consistent with howardite-eucrite-diogenite meteorites coming from Vesta.

PMID- 23128229
TI  - Observation of spatially ordered structures in a two-dimensional Rydberg gas.
AB  - The ability to control and tune interactions in ultracold atomic gases has paved
      the way for the realization of new phases of matter. So far, experiments have
      achieved a high degree of control over short-range interactions, but the
      realization of long-range interactions has become a central focus of research
      because it would open up a new realm of many-body physics. Rydberg atoms are
      highly suited to this goal because the van der Waals forces between them are many
      orders of magnitude larger than those between ground-state atoms. Consequently,
      mere laser excitation of ultracold gases can cause strongly correlated many-body
      states to emerge directly when atoms are transferred to Rydberg states. A key
      example is a quantum crystal composed of coherent superpositions of different,
      spatially ordered configurations of collective excitations. Here we use high
      resolution, in situ Rydberg atom imaging to measure directly strong correlations
      in a laser-excited, two-dimensional atomic Mott insulator. The observations
      reveal the emergence of spatially ordered excitation patterns with random
      orientation, but well-defined geometry, in the high-density components of the
      prepared many-body state. Together with a time-resolved analysis, this supports
      the description of the system in terms of a correlated quantum state of
      collective excitations delocalized throughout the gas. Our experiment
      demonstrates the potential of Rydberg gases to realize exotic phases of matter,
      thereby laying the basis for quantum simulations of quantum magnets with long
      range interactions.

PMID- 23128230
TI  - Fluvial response to abrupt global warming at the Palaeocene/Eocene boundary.
AB  - Climate strongly affects the production of sediment from mountain catchments as
      well as its transport and deposition within adjacent sedimentary basins. However,
      identifying climatic influences on basin stratigraphy is complicated by
      nonlinearities, feedback loops, lag times, buffering and convergence among
      processes within the sediment routeing system. The Palaeocene/Eocene thermal
      maximum (PETM) arguably represents the most abrupt and dramatic instance of
      global warming in the Cenozoic era and has been proposed to be a geologic
      analogue for anthropogenic climate change. Here we evaluate the fluvial response
      in western Colorado to the PETM. Concomitant with the carbon isotope excursion
      marking the PETM we document a basin-wide shift to thick, multistoried, sheets of
      sandstone characterized by variable channel dimensions, dominance of upper flow
      regime sedimentary structures, and prevalent crevasse splay deposits. This
      progradation of coarse-grained lithofacies matches model predictions for rapid
      increases in sediment flux and discharge, instigated by regional vegetation
      overturn and enhanced monsoon precipitation. Yet the change in fluvial deposition
      persisted long after the approximately 200,000-year-long PETM with its increased
      carbon dioxide levels in the atmosphere, emphasizing the strong role the
      protracted transmission of catchment responses to distant depositional systems
      has in constructing large-scale basin stratigraphy. Our results, combined with
      evidence for increased dissolved loads and terrestrial clay export to world
      oceans, indicate that the transient hyper-greenhouse climate of the PETM may
      represent a major geomorphic 'system-clearing event', involving a global
      mobilization of dissolved and solid sediment loads on Earth's surface.

PMID- 23128231
TI  - The elusive Hadean enriched reservoir revealed by 142Nd deficits in Isua Archaean
      rocks.
AB  - The first indisputable evidence for very early differentiation of the silicate
      Earth came from the extinct (146)Sm-(142)Nd chronometer. (142)Nd excesses
      measured in 3.7-billion-year (Gyr)-old rocks from Isua (southwest Greenland)
      relative to modern terrestrial samples imply their derivation from a depleted
      mantle formed in the Hadean eon (about 4,570-4,000 Gyr ago). As dictated by mass
      balance, the differentiation event responsible for the formation of the Isua
      early-depleted reservoir must also have formed a complementary enriched
      component. However, considerable efforts to find early-enriched mantle components
      in Isua have so far been unsuccessful. Here we show that the signature of the
      Hadean enriched reservoir, complementary to the depleted reservoir in Isua, is
      recorded in 3.4-Gyr-old mafic dykes intruding into the Early Archaean rocks. Five
      out of seven dykes carry (142)Nd deficits compared to the terrestrial Nd
      standard, with three samples yielding resolvable deficits down to -10.6 parts per
      million. The enriched component that we report here could have been a mantle
      reservoir that differentiated owing to the crystallization of a magma ocean, or
      could represent a mafic proto-crust that separated from the mantle more than 4.47
      Gyr ago. Our results testify to the existence of an enriched component in the
      Hadean, and may suggest that the southwest Greenland mantle preserved early
      formed heterogeneities until at least 3.4 Gyr ago.

PMID- 23128232
TI  - Fault healing promotes high-frequency earthquakes in laboratory experiments and
      on natural faults.
AB  - Faults strengthen or heal with time in stationary contact, and this healing may
      be an essential ingredient for the generation of earthquakes. In the laboratory,
      healing is thought to be the result of thermally activated mechanisms that weld
      together micrometre-sized asperity contacts on the fault surface, but the
      relationship between laboratory measures of fault healing and the seismically
      observable properties of earthquakes is at present not well defined. Here we
      report on laboratory experiments and seismological observations that show how the
      spectral properties of earthquakes vary as a function of fault healing time. In
      the laboratory, we find that increased healing causes a disproportionately large
      amount of high-frequency seismic radiation to be produced during fault rupture.
      We observe a similar connection between earthquake spectra and recurrence time
      for repeating earthquake sequences on natural faults. Healing rates depend on
      pressure, temperature and mineralogy, so the connection between seismicity and
      healing may help to explain recent observations of large megathrust earthquakes
      which indicate that energetic, high-frequency seismic radiation originates from
      locations that are distinct from the geodetically inferred locations of large
      amplitude fault slip.

PMID- 23128234
TI  - Epigenetics: Reading the second genomic code.

PMID- 23128236
TI  - Rapid fibroblast removal from high density human embryonic stem cell cultures.
AB  - Mouse embryonic fibroblasts (MEFs) were used to establish human embryonic stem
      cells (hESCs) cultures after blastocyst isolation(1). This feeder system
      maintains hESCs from undergoing spontaneous differentiation during cell
      expansion. However, this co-culture method is labor intensive, requires highly
      trained personnel, and yields low hESC purity(4). Many laboratories have
      attempted to minimize the number of feeder cells in hESC cultures (i.e.
      incorporating matrix-coated dishes or other feeder cell types(5-8)). These
      modified culture systems have shown some promise, but have not supplanted the
      standard method for culturing hESCs with mitomycin C-treated mouse embyronic
      fibroblasts in order to retard unwanted spontaneous differentiation of the hESC
      cultures. Therefore, the feeder cells used in hESC expansion should be removed
      during differentiation experiments. Although several techniques are available for
      purifying the hESC colonies (FACS, MACS, or use of drug resistant vectors) from
      feeders, these techniques are labor intensive, costly and/or destructive to the
      hESC. The aim of this project was to invent a method of purification that enables
      the harvesting of a purer population of hESCs. We have observed that in a
      confluent hESC culture, the MEF population can be removed using a simple and
      rapid aspiration of the MEF sheet. This removal is dependent on several factors,
      including lateral cell-to-cell binding of MEFs that have a lower binding affinity
      to the styrene culture dish, and the ability of the stem cell colonies to push
      the fibroblasts outward during the generation of their own "niche". The hESC were
      then examined for SSEA-4, Oct3/4 and Tra 1-81 expression up to 10 days after MEF
      removal to ensure maintenance of pluripotency. Moreover, hESC colonies were able
      to continue growing from into larger formations after MEF removal, providing an
      additional level of hESC expansion.

PMID- 23128237
TI  - Cyclopentyl methyl ether: a green co-solvent for the selective dehydration of
      lignocellulosic pentoses to furfural.
AB  - The effects of cyclopentyl methyl ether (CPME) addition during the aqueous xylose
      dehydration reaction to furfural are reported here. These investigations were
      conducted by using pure xylose and Cynara cardunculus (cardoon) lignocellulose as
      sugar source and H(2)SO(4) as catalyst. The research was also applied to aqueous
      solutions containing NaCl, since it has been previously demonstrated that NaCl
      incorporation to these reaction mixtures remarkably increases the furfural
      formation rate. It has been found that CPME incorporation inhibits the formation
      of undesired products (resins, condensation products and humins). Thus, cardoon
      lignocellulosic pentoses were selectively transformed into furfural (near 100%)
      at the following reaction conditions: 1 wt.% H(2)SO(4), 4 wt.% biomass referred
      to aqueous solution, 30 min reaction, 443 K, CPME/aqueous phase mass ratio equals
      to 2.33, and NaCl/aqueous solution mass ratio of 0.4. In contrast, no effect was
      observed for cellulosic glucose transformation into hydroxymethylfurfural and
      levulinic acid at identical reaction conditions.

PMID- 23128238
TI  - Volumetric analysis of the pons, cerebellum and hippocampi in patients with
      Alzheimer's disease.
AB  - BACKGROUND/AIMS: Our goal was to find out whether a decrease in hippocampal
      volume in Alzheimer's disease measured via magnetic resonance imaging is
      accompanied by a similar volume decrease in the pons and cerebellum. We also
      tried to evaluate whether there are any accompanying hippocampal, pontine and
      cerebellar asymmetries between the left and right side. METHODS: We performed a
      manual volumetric magnetic resonance analysis of the pons, cerebellum and
      hippocampi in 29 healthy controls and 26 patients with Alzheimer's disease,
      divided into two groups according to the Mini-Mental State Examination score.
      RESULTS: We confirmed a known decrease in hippocampal volume in Alzheimer's
      disease patients but found that there is no similar volume decrease in the pons
      or cerebellum that could serve as a radiologic diagnostic tool in Alzheimer's
      disease diagnosis. Also, there was no statistically significant right-left
      asymmetry in all three measured structures. CONCLUSION: Only hippocampal volume
      and not pontine and cerebellar volumes could serve as a magnetic resonance
      diagnostic tool in Alzheimer's disease.

PMID- 23128239
TI  - Crawling from soft to stiff matrix polarizes the cytoskeleton and
      phosphoregulates myosin-II heavy chain.
AB  - On rigid surfaces, the cytoskeleton of migrating cells is polarized, but tissue
      matrix is normally soft. We show that nonmuscle MIIB (myosin-IIB) is unpolarized
      in cells on soft matrix in 2D and also within soft 3D collagen, with rearward
      polarization of MIIB emerging only as cells migrate from soft to stiff matrix.
      Durotaxis is the tendency of cells to crawl from soft to stiff matrix, and
      durotaxis of primary mesenchymal stem cells (MSCs) proved more sensitive to MIIB
      than to the more abundant and persistently unpolarized nonmuscle MIIA (myosin
      IIA). However, MIIA has a key upstream role: in cells on soft matrix, MIIA
      appeared diffuse and mobile, whereas on stiff matrix, MIIA was strongly assembled
      in oriented stress fibers that MIIB then polarized. The difference was caused in
      part by elevated phospho-S1943-MIIA in MSCs on soft matrix, with site-specific
      mutants revealing the importance of phosphomoderated assembly of MIIA.
      Polarization is thus shown to be a highly regulated compass for mechanosensitive
      migration.

PMID- 23128240
TI  - The C-terminal unique region of desmoglein 2 inhibits its internalization via
      tail-tail interactions.
AB  - Desmosomal cadherins, desmogleins (Dsgs) and desmocollins, make up the adhesive
      core of intercellular junctions called desmosomes. A critical determinant of
      epithelial adhesive strength is the level and organization of desmosomal
      cadherins on the cell surface. The Dsg subclass of desmosomal cadherins contains
      a C-terminal unique region (Dsg unique region [DUR]) with unknown function. In
      this paper, we show that the DUR of Dsg2 stabilized Dsg2 at the cell surface by
      inhibiting its internalization and promoted strong intercellular adhesion. DUR
      also facilitated Dsg tail-tail interactions. Forced dimerization of a Dsg2 tail
      lacking the DUR led to decreased internalization, supporting the conclusion that
      these two functions of the DUR are mechanistically linked. We also show that a
      Dsg2 mutant, V977fsX1006, identified in arrhythmogenic right ventricular
      cardiomyopathy patients, led to a loss of Dsg2 tail self-association and
      underwent rapid endocytosis in cardiac muscle cells. Our observations illustrate
      a new mechanism desmosomal cadherins use to control their surface levels, a key
      factor in determining their adhesion and signaling roles.

PMID- 23128241
TI  - SUMOylation of the small GTPase ARL-13 promotes ciliary targeting of sensory
      receptors.
AB  - Primary cilia serve as cellular antenna for various sensory signaling pathways.
      However, how the sensory receptors are properly targeted to the ciliary surface
      remains poorly understood. Here, we show that UBC-9, the sole E2 small ubiquitin
      like modifier (SUMO)-conjugating enzyme, physically interacts with and SUMOylates
      the C terminus of small GTPase ARL-13, the worm orthologue of ARL13B that mutated
      in ciliopathy Joubert syndrome. Mutations that totally abolish the SUMOylation of
      ARL-13 do not affect its established role in ciliogenesis, but fail to regulate
      the proper ciliary targeting of various sensory receptors and consequently
      compromise the corresponding sensory functions. Conversely, constitutively
      SUMOylated ARL-13 fully rescues all ciliary defects of arl-13-null animals.
      Furthermore, SUMOylation modification of human ARL13B is required for the ciliary
      entry of polycystin-2, the protein mutated in autosomal dominant polycystic
      kidney disease. Our data reveal a novel but conserved role for the SUMOylation
      modification of ciliary small GTPase ARL13B in specifically regulating the proper
      ciliary targeting of various sensory receptors.

PMID- 23128242
TI  - Distinct functions of chloroplast FtsZ1 and FtsZ2 in Z-ring structure and
      remodeling.
AB  - FtsZ, a cytoskeletal GTPase, forms a contractile ring for cell division in
      bacteria and chloroplast division in plants. Whereas bacterial Z rings are
      composed of a single FtsZ, those in chloroplasts contain two distinct FtsZ
      proteins, FtsZ1 and FtsZ2, whose functional relationship is poorly understood. We
      expressed fluorescently tagged FtsZ1 and FtsZ2 in fission yeast to investigate
      their intrinsic assembly and dynamic properties. FtsZ1 and FtsZ2 formed filaments
      with differing morphologies when expressed separately. FRAP showed that FtsZ2
      filaments were less dynamic than FtsZ1 filaments and that GTPase activity was
      essential for FtsZ2 filament turnover but may not be solely responsible for FtsZ1
      turnover. When coexpressed, the proteins colocalized, consistent with coassembly,
      but exhibited an FtsZ2-like morphology. However, FtsZ1 increased FtsZ2 exchange
      into coassembled filaments. Our findings suggest that FtsZ2 is the primary
      determinant of chloroplast Z-ring structure, whereas FtsZ1 facilitates Z-ring
      remodeling. We also demonstrate that ARC3, a regulator of chloroplast Z-ring
      positioning, functions as an FtsZ1 assembly inhibitor.

PMID- 23128243
TI  - Drosophila PATJ supports adherens junction stability by modulating Myosin light
      chain activity.
AB  - The assembly and consolidation of the adherens junctions (AJs) are key events in
      the establishment of an intact epithelium. However, AJs are further modified to
      obtain flexibility for cell migration and morphogenetic movements. Intact AJs in
      turn are a prerequisite for the establishment and maintenance of apical-basal
      polarity in epithelial cells. In this study, we report that the conserved PDZ
      (PSD95, Discs large, ZO-1) domain-containing protein PATJ (Pals1-associated tight
      junction protein) was not per se crucial for the maintenance of apical-basal
      polarity in Drosophila melanogaster epithelial cells but rather regulated Myosin
      localization and phosphorylation. PATJ directly bound to the Myosin-binding
      subunit of Myosin phosphatase and decreased Myosin dephosphorylation, resulting
      in activated Myosin. Thereby, PATJ supports the stability of the Zonula Adherens.
      Notably, weakening of AJ in a PATJ mutant epithelium led first to a loss of
      Myosin from the AJ, subsequently to a disassembly of the AJ, and finally, to a
      loss of apical-basal polarity and disruption of the tissue.

PMID- 23128244
TI  - Characterization of the insertase for beta-barrel proteins of the outer
      mitochondrial membrane.
AB  - The TOB-SAM complex is an essential component of the mitochondrial outer membrane
      that mediates the insertion of beta-barrel precursor proteins into the membrane.
      We report here its isolation and determine its size, composition, and structural
      organization. The complex from Neurospora crassa was composed of Tob55-Sam50,
      Tob38-Sam35, and Tob37-Sam37 in a stoichiometry of 1:1:1 and had a molecular mass
      of 140 kD. A very minor fraction of the purified complex was associated with one
      Mdm10 protein. Using molecular homology modeling for Tob55 and cryoelectron
      microscopy reconstructions of the TOB complex, we present a model of the TOB-SAM
      complex that integrates biochemical and structural data. We discuss our results
      and the structural model in the context of a possible mechanism of the TOB
      insertase.

PMID- 23128226
TI  - An integrated map of genetic variation from 1,092 human genomes.
AB  - By characterizing the geographic and functional spectrum of human genetic
      variation, the 1000 Genomes Project aims to build a resource to help to
      understand the genetic contribution to disease. Here we describe the genomes of
      1,092 individuals from 14 populations, constructed using a combination of low
      coverage whole-genome and exome sequencing. By developing methods to integrate
      information across several algorithms and diverse data sources, we provide a
      validated haplotype map of 38 million single nucleotide polymorphisms, 1.4
      million short insertions and deletions, and more than 14,000 larger deletions. We
      show that individuals from different populations carry different profiles of rare
      and common variants, and that low-frequency variants show substantial geographic
      differentiation, which is further increased by the action of purifying selection.
      We show that evolutionary conservation and coding consequence are key
      determinants of the strength of purifying selection, that rare-variant load
      varies substantially across biological pathways, and that each individual
      contains hundreds of rare non-coding variants at conserved sites, such as motif
      disrupting changes in transcription-factor-binding sites. This resource, which
      captures up to 98% of accessible single nucleotide polymorphisms at a frequency
      of 1% in related populations, enables analysis of common and low-frequency
      variants in individuals from diverse, including admixed, populations.

PMID- 23128246
TI  - Changing trends in well differentiated thyroid carcinoma over eight decades.
AB  - INTRODUCTION: The incidence of well differentiated thyroid cancer (WDTC) is
      rising in the USA. The objective of this study is to present the changes in
      incidence, presentation, management and outcomes of WDTC within our institution
      over the past 8 decades. METHODS: 2797 patients managed between 1932 and 2005 at
      Memorial Sloan Kettering Cancer Center were identified from our institutional
      database. RESULTS: There has been an increase in the number of patients managed
      per decade. Although the median age was 45 years, patients managed post-1985 were
      more likely to be over 45 years (53% versus 44%, p < 0.001). The percentage of
      women increased from 68% to 72% (p = 0.026), and the percentage of papillary
      carcinomas also increased, from 78% to 92%, p < 0.001. An increase in early stage
      tumors was observed with pT1 lesions increasing from 19% to 48%. Patients in the
      latter cohort were less likely to have thyroid lobectomy (29% versus 72%, p <
      0.001). There was a significant change in the use of RRA, with 8% of the early
      versus 44% of the latter group receiving post-operative RRA (p < 0.001). Since
      the introduction of risk group stratification disease specific survival (DSS) has
      not changed significantly. With a median follow up of 90 months, 10 year DSS
      rates were below 90% in the cohort managed prior to the 1970s, which rose to >95%
      thereafter (p < 0.001). CONCLUSIONS: Older patients with earlier stage disease
      present an increasing workload for surgical oncologists. Excellent outcomes
      remain unchanged despite increasingly aggressive surgical and medical management.

PMID- 23128247
TI  - Matrix metalloproteinase-9 gene polymorphisms and chronic kidney disease.
AB  - BACKGROUND: The aim of this study was to explore the associations between the
      prevalence of chronic kidney disease (CKD) and polymorphisms in the genes
      encoding matrix metalloproteinases (MMPs) and tissue inhibitor of matrix
      metalloproteinases (TIMPs). MMPs degrade extracellular matrix proteins in the
      glomerulus, and play important roles in kidney disease progression. METHODS: DNA
      samples from 3,309 subjects aged 35-69 years were genotyped for 10 potentially
      functional polymorphisms in MMP and TIMP genes. The prevalence of CKD (estimated
      glomerular filtration rate <60 ml/min/1.73 m(2)) was compared among the
      genotypes. RESULTS: The prevalence of CKD decreased significantly with the number
      of minor alleles in MMP9 C-1562T (odds ratios (ORs) 0.77 for CT and 0.65 for TT
      compared with CC; p for trend = 0.023) and MMP9 R668Q (ORs, 0.79 for RQ and 0.64
      for QQ compared with RR; p for trend = 0.024). The haplotype MMP9 
      1562T/279R/668Q showed a reduced risk for CKD compared with the most common 
      1562C/279R/668R (OR 0.77, p = 0.008), and the genotype combination -1562TT/
      279RR/668QQ showed a halved risk for CKD compared with major allele homozygous 
      1562CC/279RR/668RR (OR 0.53, p = 0.091). CONCLUSION: The potentially functional
      polymorphisms of MMP9 were associated with the prevalence of CKD in a large
      Japanese population. These genotypes have been reported to increase MMP9
      expression, supporting the hypothesis that MMP-9 has a protective role in the
      progression of kidney diseases.

PMID- 23128233
TI  - Host-microbe interactions have shaped the genetic architecture of inflammatory
      bowel disease.
AB  - Crohn's disease and ulcerative colitis, the two common forms of inflammatory
      bowel disease (IBD), affect over 2.5 million people of European ancestry, with
      rising prevalence in other populations. Genome-wide association studies and
      subsequent meta-analyses of these two diseases as separate phenotypes have
      implicated previously unsuspected mechanisms, such as autophagy, in their
      pathogenesis and showed that some IBD loci are shared with other inflammatory
      diseases. Here we expand on the knowledge of relevant pathways by undertaking a
      meta-analysis of Crohn's disease and ulcerative colitis genome-wide association
      scans, followed by extensive validation of significant findings, with a combined
      total of more than 75,000 cases and controls. We identify 71 new associations,
      for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most
      loci contribute to both phenotypes, and both directional (consistently favouring
      one allele over the course of human history) and balancing (favouring the
      retention of both alleles within populations) selection effects are evident. Many
      IBD loci are also implicated in other immune-mediated disorders, most notably
      with ankylosing spondylitis and psoriasis. We also observe considerable overlap
      between susceptibility loci for IBD and mycobacterial infection. Gene co
      expression network analysis emphasizes this relationship, with pathways shared
      between host responses to mycobacteria and those predisposing to IBD.

PMID- 23128248
TI  - Tackling childhood overweight and obesity: thresholds and beyond.

PMID- 23128249
TI  - Morphogenesis of rete ridges in human oral mucosa: a pioneering morphological and
      immunohistochemical study.
AB  - OBJECTIVE: One of the major impediments in tissue-engineered oral mucosa (TEOM)
      is the lack of rete ridge (RR) structures that can weaken the connection between
      the epidermis and dermis. This study aimed to investigate the native morphology
      of RRs as well as the expression of extracellular signal-regulated kinase 1/2
      (ERK1/2), Ki67, and keratin-19, which are related to cell mechanotransduction,
      proliferation, and stemness in the oral epidermis, respectively. METHODS: RR
      characteristics, including type, density, length, and width, were analyzed in the
      masticatory mucosa (Mm) and lining mucosa (Lm) sites of 52 specimens. The
      expression of ERK1/2, Ki67, and keratin-19 was assessed by immunohistochemistry.
      ERK1/2 activation by masticatory stimuli was confirmed in vitro by loading
      pressure onto cultured keratinocytes isolated from the specimens. RESULTS: Three
      types of RR were found. The RRs in the Mm and Lm differed. The length and
      percentage of ERK1/2-positive (%ERK1/2+) basal layer cells had a negative
      correlation (p = 0.004), whereas the length and %Ki67+ basal layer cells had a
      positive correlation (p = 0.013). The %ERK1/2+ basal layer cells and %keratin-19+
      basal layer cells had a negative relationship (p = 0.011). ERK1/2 activation in
      the oral epithelium was induced by pressure and propagated in cultured
      keratinocytes. CONCLUSION: RRs are longer in the Mm, which may result from the
      topical basal cell proliferation and migration induced by masticatory pressure
      via ERK1/2 activation. Our findings preliminarily interpret RR histomorphology as
      influenced by oral masticatory pressure. Results may benefit future studies on RR
      development and reconstruction in TEOM models to enhance the epidermis-dermis
      connection.

PMID- 23128251
TI  - [Hospitalizations due to ambulatory care-sensitive conditions in the Federal
      District, Brazil, 2008].
AB  - OBJECTIVE: To analyze hospitalization rates due to ambulatory care-sensitive
      conditions. METHODS: The study used data from the Hospital Database of the
      Brazilian National Health System corresponding to the Federal District in the
      year of 2008. The main diagnosis for hospitalization was analyzed based on the
      International Classification of Diseases, and absolute frequency, proportion and
      coefficient were calculated according to causes, age groups and sex. RESULTS: The
      ambulatory care-sensitive conditions (ACSC) represented approximately 20% of the
      hospital admissions in the National Health System. The most frequent conditions
      were: gastroenteritis (2.4%), heart failure (2.3%), and kidney and urinary tract
      infection (2.1%). The following aspects were verified: significant
      hospitalization rates due to ACSC in the infant group (< 1 year of age), an
      important reduction in the following age groups (1 to 29 years), and a gradual
      increase until the more advanced ages. Compared to men, hospitalization rates
      were slightly higher among young women (20 to 29 years) and lower among women
      older than 49 years. CONCLUSIONS: Hospitalizations due to ACSC represented 19.5%
      of all hospital admissions in the Federal District (2008), and the main causes of
      hospitalizations were gastroenteritis, heart failure and kidney and urinary tract
      infection. The effectiveness of primary health care in preventing these events in
      the Federal District is discussed.

PMID- 23128253
TI  - [Evaluation of health service providers by consumers through the Analytic
      Hierarchy Process Method].
AB  - OBJECTIVE: To assess the quality of services offered by health service providers,
      according to the perception of consumers. METHODS: A cross-sectional study with
      360 consumers from seven health service providers in the metropolitan area of
      Curitiba, PR, in 2008, was performed. An individual questionnaire measuring the
      consumers' preferences in relation to six attributes (location of service points;
      effectiveness of doctors, clinics and hospitals; promptness and kindness when
      caring for patients and family members; ease of access to the authorization forms
      for consultations; price; diversity of available doctors, clinics and hospitals)
      for each one of the analyzed health service providers was carried out. The
      Analytic Hierarchy Process (AHP), a multiple criteria tool for decision analysis
      and planning, was used to analyze the responses. RESULTS: The attribute most
      valued by the consumers was "price". The companies were grouped into two sets,
      regarding the mentioned attributes: two had lower preference (between 19% and
      23%) and five, higher preference (around 10% each). CONCLUSIONS: With this type
      of research, health service providers could reshape their structures, processes,
      prices and accredited networks, in order to improve their market strategy.

PMID- 23128250
TI  - HPV16/18 E5, a promising candidate for cervical cancer vaccines, affects SCPs,
      cell proliferation and cell cycle, and forms a potential network with E6 and E7.
AB  - The spindle checkpoint proteins (SCPs), which sense the existence of misaligned
      sister chromatids during mitosis and meiosis, are essential for cell
      proliferation and differentiation. Therefore, the role of SCPs in carcinogenesis
      is gaining increased attention. In this study, we analysed the expression of Bub1
      and Mad2 in clinical samples by immunohistochemistry (IHC) during the development
      of cervical cancer (CC), and we explored the interaction of Bub1/Mad2 with
      different proteins through immunoprecipitation (IP). Furthermore, we analysed the
      characteristics of four different cell models of human papillomavirus (HPV)16/18
      E5. We demonstrated that with the progression of CC, the expression of Bub1 and
      Mad2 was gradually reduced under the influence of HPVE5. Overexpression of
      HPV16/18 E5 significantly increased cell proliferation, as well as the percentage
      of cells in the S phase. In addition, the levels of p21, Bub1 and Mad2 were
      markedly decreased in E5-expressing cells. Therefore, HPV16/18 E5 plays a
      critical role in carcinogenesis and is a potential therapeutic target in CC
      treatment.

PMID- 23128252
TI  - [Effectiveness of a quality control program in mammography for the Brazilian
      National Health System].
AB  - OBJECTIVE: To assess the effectiveness of a quality control program in
      mammography services of the Brazilian National Health System (SUS). METHODS: A
      prospective study using temporal analysis of a health surveillance action was
      conducted. A total of 35 service providers that had mammography equipment in
      operation and regularly performed exams between 2007 and 2009 in the state of
      Goias, Central-Western Brazil, participated in this study. Services were assessed
      during three site visits by performance testing of mammography equipment, film
      processors, and other materials, and image quality and entrance surface dose in a
      phantom were also assessed. Each service was scored according to the percentage
      of tests that conformed to standards. RESULTS: The mean percentage for compliance
      among the participating service providers were 64.1% (+/- 13.3%) in the first
      visit, 68.4% (+/- 15.9%) in the second, and 77.1% (+/- 13.3%) in the third (p <
      0.001). The main improvements resulted from adjustments to the breast compression
      force, the automatic exposure control system, and the alignment of the
      compression paddle. The doses measured were within the conformity range in 80% of
      the services assessed. CONCLUSIONS: The implementation of this program in the
      mammography services was effective at improving the operational parameters of the
      mammography machines, although 40% of the services did not reach the acceptable
      level of 70%. This result indicates the need to continue this health surveillance
      action.

PMID- 23128254
TI  - [Doctors, lawyers and pharmaceutical industry on health lawsuits in Minas Gerais,
      Southeastern Brazil].
AB  - OBJECTIVE: To describe the relationship between the prescribing doctor, lawyer
      and pharmaceutical industry in lawsuits against the state. METHODS: Retrospective
      descriptive study based on data from administrative files, relating to lawsuits
      involving medicine demands, in the state of Minas Gerais, Southeastern Brazil,
      from October 1999 to October 2009. RESULTS: A total of 2,412 lawsuits were
      analyzed with 2,880 medicine requests, including 18 different drugs, 12 of them
      provided through Pharmaceutical Policies of the Brazilian National Health System
      (SUS). The most frequent medicines requested included were adalimumab,
      etanercept, infliximab, insulin glargine and tiotropium bromide. The main
      diseases were rheumatoid arthritis, ankylosing spondylitis, diabetes mellitus,
      and chronic obstructive pulmonary disease. Private lawyers and doctors were
      predominant. The results revealed the association between doctors and law offices
      on drug requests. Among the lawsuits filed by the office A, 43.6% had a single
      prescriber to adalimumab, while 29 doctors were responsible for 40.2% of the same
      drug prescriptions. A single doctor was responsible for 16.5% of the adalimumab
      prescriptions, being requested through lawsuits filed by a single private law
      office in 44.8% of legal proceedings. CONCLUSIONS: A greater representation of
      doctors and lawyers from the private sector can hinder equity in health. The
      results revealed the association between doctors and law offices on drug
      requests. This is an indication that justice and medical practice have been used,
      at certain times, to serve the interests of the pharmaceutical industry.

PMID- 23128255
TI  - [Legal decisions on access to medicines in Pernambuco, Northeastern Brazil].
AB  - OBJECTIVE: To analyze decisions from the legal system concerning the population's
      access to medicines within the Brazilian Public Health System through judicial
      channels, with regard to decision-making criteria and possible political and
      economic pressure. METHODS: This was a descriptive retrospective study on
      documents with a quantitative and qualitative approach. Data were gathered from
      the State of Pernambuco Superintendency for Pharmaceutical Care, and the data
      sources used were 105 lawsuits and administrative reports between January and
      June 2009. It was ascertained which medications have a patent or patent request
      in the database of the Brazilian Patent Office (INPI), in order to identify the
      frequency with which patents feature in lawsuits. The data obtained were
      classified according to Anatomical and Therapeutic Chemical System. To analyze
      the judicial decisions, the theory of autopoietic social systems was used.
      RESULTS: There were lawsuits involving 134 medications, with an estimated value
      of R$ 4.5 million for attending the treatments requested. 70.9% of the
      medications had a patent or a patent request and they were concentrated in three
      therapeutic classes: antineoplastic and immunomodulating agents; digestive tract
      and metabolism; and sensory organs. Six central ideas within judges' decision
      making criteria were identified (the federal constitution and medical
      prescriptions), along with pressure between the legal, economic and political
      systems concerning access to medications. CONCLUSIONS: The analysis on judicial
      decisions based on the theory of autopoietic social systems made it possible to
      identify mutual stimulation (dependency) between the legal system and other
      social systems in relation to the issue of citizens' access to medications. This
      dependency was represented by the federal constitution and intellectual property.
      The federal constitution and medical prescription were identified as decision
      making criteria in lawsuits. Intellectual property represented possible political
      and economic pressure, especially in cases of launching medications into the
      market.

PMID- 23128256
TI  - [Risk and sanitary safety: analysis on medical product reprocessing in hospitals
      in Salvador, Northeastern Brazil].
AB  - OBJECTIVE: To analyze the technical conditions for medical product reprocessing
      in hospitals. METHODS: This was a descriptive study on multiple cases in
      materials and sterilization centers at four hospitals in the city of Salvador,
      Southeastern Brazil, in 2010. Semi-structured interviews were conducted and
      direct observations were made, based on a regulatory model for medical product
      reprocessing that was drawn up with the technique of consensus verification as
      the reference standard. The analytical categories used in this study were:
      management of the practice of medical product reprocessing; reprocessing
      protocols; monitoring of the sterilization process; and capacity for product
      tracking. These categories were scored according to their degree of conformity
      with the regulatory model for reprocessing used. RESULTS: General inadequacy of
      the technical conditions for medical product reprocessing was observed, with
      regard to the structural conditions of the materials and sterilization centers
      studied and the work process conditions, along with organizational and managerial
      difficulties that interfered with the practices analyzed. CONCLUSIONS: The
      practices of medical product reprocessing in the hospitals analyzed constitute a
      risk for the patient users. Risk management systems need to be introduced in
      these hospitals, with greater sanitary control by the state, in order to protect
      patients' health.

PMID- 23128257
TI  - [Illicit substances use by Portuguese adolescents].
AB  - OBJECTIVE: To describe the prevalence of illicit drug consumption among
      adolescents and the motives that led these adolescents to try them. METHODS:
      Cross-sectional study with 2,499 adolescents aged 17 years, based on a cohort
      called EPITeen, which was started in 2003/2004 with adolescents born in 1990 who
      studied in public and private schools of the city of Porto, Portugal. A new
      assessment was carried out in 2007/2008: 1,716 adolescents (79.5%) were recovered
      and 783 new participants were evaluated. Information about social and demographic
      characteristics, family and personal history of diseases and behaviours were
      obtained through self-administered structured questionnaires. The chi-square test
      was used to test the associations. The statistical analysis was performed in the
      program SPSS(r) version 17. RESULTS: Of the adolescents, 14.6% had tried drugs at
      least once in their lives. The most tried illicit drug was cannabis (12.5%),
      followed by alcohol together with cannabis (5.5%) and tranquilizers (1.7%). The
      most cited reason for trying drugs was curiosity (77.5%). Friends were the most
      frequently cited form of obtaining drugs and the school was seen by 24.2% of the
      adolescents as a place where it was possible to buy cannabis. CONCLUSIONS: The
      results support the need to intervene at an early age and suggest that this
      intervention should be integrated with strategies targeted at other risk
      behaviors, particularly in schools.

PMID- 23128258
TI  - [Maslach Burnout Inventory - Student Survey: Portugal-Brazil cross-cultural
      adaptation].
AB  - OBJECTIVE: To perform a cross-cultural adaptation of the Portuguese version of
      the Maslach Burnout Inventory for students (MBI-SS), and investigate its
      reliability, validity and cross-cultural invariance. METHODS: The face validity
      involved the participation of a multidisciplinary team. Content validity was
      performed. The Portuguese version was completed in 2009, on the internet, by 958
      Brazilian and 556 Portuguese university students from the urban area.
      Confirmatory factor analysis was carried out using as fit indices: the chi2/df,
      the Comparative Fit Index (CFI), the Goodness of Fit Index (GFI) and the Root
      Mean Square Error of Approximation (RMSEA). To verify the stability of the factor
      solution according to the original English version, cross-validation was
      performed in 2/3 of the total sample and replicated in the remaining 1/3.
      Convergent validity was estimated by the average variance extracted and composite
      reliability. The discriminant validity was assessed, and the internal consistency
      was estimated by the Cronbach's alpha coefficient. Concurrent validity was
      estimated by the correlational analysis of the mean scores of the Portuguese
      version and the Copenhagen Burnout Inventory, and the divergent validity was
      compared to the Beck Depression Inventory. The invariance of the model between
      the Brazilian and the Portuguese samples was assessed. RESULTS: The three-factor
      model of Exhaustion, Disengagement and Efficacy showed good fit (c 2/df = 8.498,
      CFI = 0.916, GFI = 0.902, RMSEA = 0.086). The factor structure was stable
      (lambda:chi2dif = 11.383, p = 0.50; Cov: chi2dif = 6.479, p = 0.372; Residues:
      chi2dif = 21.514, p = 0.121). Adequate convergent validity (VEM = 0.45;0.64, CC =
      0.82;0.88), discriminant (rho2 = 0.06;0.33) and internal consistency (alpha =
      0.83;0.88) were observed. The concurrent validity of the Portuguese version with
      the Copenhagen Inventory was adequate (r = 0.21, 0.74). The assessment of the
      divergent validity was impaired by the approach of the theoretical concept of the
      dimensions Exhaustion and Disengagement of the Portuguese version with the Beck
      Depression Inventory. Invariance of the instrument between the Brazilian and
      Portuguese samples was not observed (lambda:chi2dif = 84.768, p<0.001; Cov:
      chi2dif = 129.206, p < 0.001; Residues: chi2dif = 518.760, p < 0.001).
      CONCLUSIONS: The Portuguese version of the Maslach Burnout Inventory for students
      showed adequate reliability and validity, but its factor structure was not
      invariant between the countries, indicating the absence of cross-cultural
      stability.

PMID- 23128259
TI  - [Prevalence of asthma and risk factors associated: population based study in Sao
      Paulo, Southeastern Brazil, 2008-2009].
AB  - OBJECTIVE: To assess the prevalence of asthma and risk factors associated in
      children and adolescents. METHODS: Population-based cross-sectional study with
      1,185 female and male children and adolescents carried out in the city of Sao
      Paulo, Southeastern Brazil, from 2008 to 2009. Data were collected through home
      interviews. Respondents were selected from two-stage (census tract, household)
      cluster random sampling stratified by gender and age. Multiple Poisson regression
      was used in the adjusted analysis between the outcome and socioeconomic,
      demographic, lifestyle and health condition variables. RESULTS: Of all
      respondents, 9.1% (95%CI 7.0;11.7) reported asthma. After adjustment, the
      following variables were found independently associated with asthma: age (0 to 4
      years vs. 15 to 19) (PR 3.18, 95%CI 1.20;8.42); age (5 to 9 years vs. 15 to 19)
      (PR 6.37, 95%CI 2.64;15.39); age (10 to 14 years vs. 15 to 19) (PR 4.51, 95%CI
      1.95;10.40); allergy (yes vs. no) (PR 2.22, 95%CI 1.24;4.00); rhinitis (yes vs.
      no) (PR 2.13, 95%CI 1.22;3.73); health conditions in the 15 days preceding the
      interview (yes vs. no) (PR 1.96, 95%CI 1.23;3.11); number of rooms in the
      household (1 to 3 vs. 4 and more) (PR 1.67, 95%CI 1.05;2.66); and skin color
      (black and mixed vs. white) (PR 2.00, 95%CI 1.14;3.49). CONCLUSIONS: This study
      showed the importance of factors associated with asthma including rhinitis and
      allergy; age between 5 to 9 years old; black and mixed skin color; and household
      with few rooms. Frequent health problems are seen as a common consequence of
      asthma.

PMID- 23128260
TI  - Association between tooth loss and obesity in Brazilian adults: a population
      based study.
AB  - OBJECTIVE: To examine the association between tooth loss and general and central
      obesity among adults. METHODS: Population-based cross-sectional study with 1,720
      adults aged 20 to 59 years from Florianopolis, Southern Brazil. Home interviews
      were performed and anthropometric measures were taken. Information on
      sociodemographic data, self-reported diabetes, self-reported number of teeth,
      central obesity (waist circumference [WC] > 88 cm in women and > 102 cm in men)
      and general obesity (body mass index [BMI] >= 30 kg/m2) was collected. We used
      multivariable Poisson regression models to assess the association between general
      and central obesity and tooth loss after controlling for confounders. We also
      performed simple and multiple linear regressions by using BMI and WC as
      continuous variables. Interaction between age and tooth loss was also assessed.
      RESULTS: The mean BMI was 25.9 kg/m2 (95%CI 25.6;26.2) in men and 25.4 kg/m2
      (95%CI 25.0;25.7) in women. The mean WC was 79.3 cm (95%CI 78.4;80.1) in men and
      88.4 cm (95%CI 87.6;89.2) in women. A positive association was found between the
      presence of less than 10 teeth in at least one arch and increased mean BMI and WC
      after adjusting for education level, self-reported diabetes, gender and monthly
      per capita income. However, this association was lost when the variable age was
      included in the model. The prevalence of general obesity was 50% higher in those
      with less than 10 teeth in at least one arch when compared with those with 10 or
      more teeth in both arches after adjusting for education level, self-reported
      diabetes and monthly per capita family income. However, the statistical
      significance was lost after controlling for age. CONCLUSIONS: Obesity was
      associated with number of teeth, though it depended on the participants' age
      groups.

PMID- 23128261
TI  - [Community health workers' attitudes and beliefs toward the elderly].
AB  - OBJECTIVE: To describe community health workers' attitudes and beliefs toward the
      elderly. METHODS: Cross-sectional descriptive study conducted in with 213
      community health workers (CHWs) at 12 primary care units and 29 family health
      centers in the city of Marilia, State of Sao Paulo, Southeastern Brazil, in 2010.
      Data were collected by means of a sociodemographic questionnaire, a scale of
      attitudes toward aging (Neri Scale), and a questionnaire to assess gerontological
      knowledge (the Palmore-Neri-Cachioni Aging Quiz). The Statistical Package for the
      Social Sciences v. 16.0 was used for data analysis. RESULTS: Community health
      workers predominantly consisted of young female adults, married, with more than
      12 years of schooling and who worked in this activity for over 6 years. Most CHWs
      reported having experience with elderly people and having elderly people in the
      family. However, less than half of them received training on the topic of aging.
      As for attitudes towards the elderly, CHWs stressed both positive aspects such as
      their wisdom and generosity and negative aspects such as slowness and strictness.
      They showed low gerontological knowledge, which was directly associated with the
      training received. Many CHWs stereotyped the elderly as dissatisfied and
      dependent. CONCLUSIONS: Changing attitudes and improving knowledge on aging are
      critical for meeting health care demands of elderly people. More appropriate
      training of CHWs is key for providing adequate primary care to elderly
      population.

PMID- 23128262
TI  - Risk perception about zoonoses in immigrants and Italian workers in Northwestern
      Italy.
AB  - OBJECTIVE: To assess factors associated with a low risk perception of zoonoses
      and to identify the gaps in knowledge about transmission and prevention of
      zoonoses in immigrant and Italian workers. METHODS: A cross-sectional study with
      175 workers in the agro-livestock and agro-food industry in Piemonte, Italy, was
      carried out. Data were collected with a semi-structured questionnaire based on
      knowledge, attitudes and practices (KAP) survey. We calculated proportions and
      used chi-square tests and odds ratios to assess associations. Eight individual
      interviews with key informants on immigration and public health in Piemonte were
      carried out. RESULTS: Participants were 82 (47%) Italians and 93 (53%)
      immigrants. Immigrants were from Romania, Morocco, Albania, India, China,
      Argentina, Peru, Macedonia, Ivory Coast, Ukraine and Colombia. The study revealed
      significant differences in risk perception at work (p = 0.001). We found
      associations between "not having correct knowledge about zoonoses" and the
      following variables: i. "being immigrant" OR = 4.1 (95%CI 1.7;9.8 p <= 0.01); ii.
      "working in the livestock industry" OR = 2.9 (95%CI 1.2;15.4 p = 0.01); and iii.
      "being an unqualified worker" OR = 4.4 (95%CI 2.9;15.4 p <= 0.01). Another strong
      association was found between being immigrant and having a low job qualification
      OR = 6.7 (IC95% 2.9 - 15.4 p <= 0.01). Asian immigrants were the group with the
      highest frequency of risky behaviours and the lowest level of knowledge about
      zoonoses. CONCLUSIONS: Our results indicate that there were differences in risk
      perception of zoonoses between the groups participating in our study. These
      results suggest that immigrant status can be considered a risk factor for having
      lower risk perception and lower level of knowledge of zoonoses at work. There is
      a relationship between this specific knowledge of zoonoses and lack of training
      and instruction among migrant populations. Our results stress the need for
      developing education programs on zoonoses prevention among the immigrant
      population in Piemonte, Italy.

PMID- 23128263
TI  - Bionomics of Culex quinquefasciatus within urban areas of Rio de Janeiro,
      Southeastern Brazil.
AB  - OBJECTIVE: To evaluate density, parity rates, daily survival and longevity of
      natural populations of Culex quinquefasciatus in three neighborhoods with
      distinct socio-economic and infrastructure profiles. METHODS: Mosquito
      collections of the Culex quinquefasciatus species were performed weekly during
      two four month periods, from August to November 2008 (spring) and March to June
      2009 (fall), in a favela (slum), a suburban area and a middle class area of Rio
      de Janeiro, Southeastern Brazil. Collections were performed with backpack
      aspirators, in 20 randomly selected houses in each area per week, during 15-20
      minutes per house. Ovaries were removed from captured females and classified as
      initial, intermediary or final stage. Furthermore, females were dissected for
      determination of parity based on the condition of the tracheal system. Mosquito
      survival rate and longevity were estimated on a per month basis for each
      neighborhood. RESULTS: We collected a total of 2,062 Culex quinquefasciatus, but
      monthly vector density was not correlated with temperature and rainfall. We
      dissected the ovaries of 625 Culex quinquefasciatus, and overall, there was a
      higher proportion of nulliparous females during the dryer months, while gravid
      females were more frequent in rainy months. In the middle class neighborhood, the
      parity rate reached up to 93.75% with survivorship of 0.979. Lower parity and
      survival rates were obtained in the suburban area (as low as 36.4% parity and
      0.711 daily survival). Up to 84.7% of Culex quinquefasciatus females could
      survive the eight day period needed to complete West Nile Virus incubation.
      CONCLUSIONS: The survival rate of Culex quinquefasciatus varied significantly
      between the neighborhoods. This suggests that vectorial capacity and disease
      transmission risk may vary greatly between different urban areas, which is
      potentially useful information for vector control programs.

PMID- 23128264
TI  - [Health and informal work conditions among recyclers in the rural area of
      Medellin, Colombia, 2008].
AB  - OBJECTIVE: To characterize the work, health and occupational risk conditions of
      recyclers from the rural area. METHODS: Cross-sectional study, with the
      participation of one hundred informal recyclers in five corregimientos (small
      administrative units) of Medellin in 2008. The source of information was primary:
      a structured survey on work, health and occupational risk conditions and also on
      perceived morbidity, which enabled to characterize the population's risks through
      descriptive statistics and approach the relationships and associations of the
      risks with the morbidity in the population. RESULTS: One hundred and four people
      were engaged in recycling, and 100 of them were included in the study: 34 people
      belonged to community-based organizations and 66 people worked independently.
      Social security affiliation, fulfillment of basic needs, work satisfaction,
      access to training activities and periodic provision of work supplies presented
      differences according to group (p < 0.05). The biological risks, associated with
      inadequate body postures, and physical and chemical risks had a particular
      frequency of exposure according to group. The knowledge and use of safety
      measures for occupational risks differed statistically among the analyzed groups
      (p < 0.05). CONCLUSIONS: Recyclers are a potential support to integral waste
      management in rural areas of Medellin, although the informal nature of their work
      exposes them to working conditions that directly affect their health and the
      health of their families. The social recognition of recycling goes hand in hand
      with the improvement in the working conditions of the people engaged in this
      activity. The environmental recycling workers, even if belonging to a union, have
      precarious work and health conditions. The transformation of these conditions
      should be one of the State's priorities.

PMID- 23128265
TI  - [RSI/WRMSD in the third decade after restructuring of banking: new associated
      factors?].
AB  - OBJECTIVE: To estimate the prevalence of cases suggestive of repetitive strain
      injury/work-related musculoskeletal disorders (RSI/WRMSD), three decades after
      restructuring of banking. METHODS: This was a cross-sectional study on 356
      employees in 27 bank branches of public and private banks in Porto Alegre,
      Southern Brazil, between April and August 2009. After crude statistical analysis,
      adjustments were made using a Poisson regression model with robust variance and a
      three-level hierarchy that incorporated the design structure and adjustments for
      the clusters. The results were stratified according to the size of the bank
      branch and were dichotomized (> 25; <= 25 employees). RESULTS: The prevalence of
      cases suggestive of RSI/WRMSD was lower among the men (PR = 0.62; 95%CI: 0.47
      0.81). Workers aged 26 to 45 years (PR = 2.51; 95%CI 1.02;6.14) presented greater
      prevalence of this outcome. Individuals with postgraduate qualifications (PR =
      0.45; 95%CI 0.22;0.90) and length of time in the job between 5.1 and 15 years (PR
      = 0.62; 95%CI 0.47;0.81) presented protection against RSI/WRMSD. On stratifying
      the analyses according to size, it was found that age, income and length of time
      in the job remained associated in branches with 25 employees or fewer, while in
      branches with more than 25 employees, sex and schooling level were associated
      with the outcome. CONCLUSIONS: The characteristics of importance in relation to
      bank employees who become ill due to rsi/wrmsd seem to be different today from
      those that were known historically. greater attention to organizing work and
      management strategies should be taken into consideration in drawing up illness
      prevention programs for banking work.

PMID- 23128266
TI  - [Staying awake: truck drivers' vulnerability in Rio Grande do Sul, Southern
      Brazil].
AB  - OBJECTIVE: To analyze factors associated with the use of stimulants by truck
      drivers to stay awake. METHODS: A survey with 854 drivers was carried out at
      eight truck stops (seven gas stations and one border patrol post) located at five
      cities in the State of Rio Grande do Sul (Southern Brazil) in 2006. The outcome
      "amphetamine use" was categorized as "yes" or "no". Poisson regression analysis
      with robust variance was conducted in order to select the variables that would be
      included in the model, which was composed of variables regarding socioeconomic
      and demographic characteristics, information on the profession and on alcohol
      consumption. RESULTS: Amphetamine use to stay awake was reported by 12.4% of the
      truck drivers, either in isolation or in combination with other substances
      (coffee, guarana powder, energy drinks, snorted cocaine). Amphetamine was the
      most cited substance by those who consumed something to stay awake. The
      consumption of alcoholic drinks was mentioned by more than 70% of the
      interviewees; among those who drink, 45.1% reported that they use alcohol at
      least once a week. Amphetamine use was associated with younger age groups, wage
      increase, longer trips, and alcohol use. CONCLUSIONS: The increase in the truck
      drivers' wages implies increased workloads. This produces physical and emotional
      stress, which makes the truck drivers search for a temporary solution in the
      consumption of stimulants. The reduction in the abusive consumption of alcohol
      and in the illicit use of substances like amphetamines by professional drivers
      depends not only on policies addressing prevention and treatment for drug abuse,
      but also on integrated policies ensuring better working and health conditions to
      the truck drivers.

PMID- 23128267
TI  - [Multiple authorship: growth or inflationary bubble?].
AB  - OBJECTIVE: To analyze the increase in number of authors per article in Brazilian
      scientific journals on public health. METHODS: Articles published between 1999
      and 2010 in six journals on public health and one medical journal (for
      comparison) from SciELO with Qualis (Capes) classification equal or superior to B
      1, were searched on the LILACS database. The evolution of the median number of
      authors/article and the proportion of articles with more than four authors were
      evaluated. The association between the the triennium of publication and the
      presence of four or more authors per paper was estimated through the Mantel
      Haenzel odds ratio, adjusted for the type of journal. RESULTS: An increase of the
      median number of authors and the proportion of articles with more than four
      authors was observed in all journals, especially in the last triennium. The odds
      ratio for articles with four or more authors, adjusted for the type of journal,
      were: second triennium 1.3 (95%CI 1.1;1.4); third triennium 1.5 (95%CI 1.3;1.8),
      fourth triennium 2.39 (95%CI 2.1;2.8). CONCLUSIONS: Scientific journals on public
      health have shown an increase in the number of authors per article over the
      years, regardless of editorial orientation.

PMID- 23128268
TI  - Prevalence of alcohol and tobacco use among Brazilian adolescents: a systematic
      review.
AB  - OBJECTIVE: To analyze alcohol and tobacco use among Brazilian adolescents and
      identify higher-risk subgroups. METHODS: A systematic review of the literature
      was conducted. Searches were performed using four databases (LILACS, MEDLINE
      /PubMed, Web of Science, and Google Scholar), specialized websites and the
      references cited in retrieved articles. The search was done in English and
      Portuguese and there was no limit on the year of publication (up to June 2011).
      From the search, 59 studies met all the inclusion criteria: to involve Brazilian
      adolescents aged 10-19 years; to assess the prevalence of alcohol and/or tobacco
      use; to use questionnaires or structured interviews to measure the variables of
      interest; and to be a school or population-based study that used methodological
      procedures to ensure representativeness of the target population (i.e. random
      sampling). RESULTS: The prevalence of current alcohol use (at the time of the
      investigation or in the previous month) ranged from 23.0% to 67.7%. The mean
      prevalence was 34.9% (reflecting the central trend of the estimates found in the
      studies). The prevalence of current tobacco use ranged from 2.4% to 22.0%, and
      the mean prevalence was 9.3%. A large proportion of the studies estimated
      prevalences of frequent alcohol use (66.7%) and heavy alcohol use (36.8%) of more
      than 10%. However, most studies found prevalences of frequent and heavy tobacco
      use of less than 10%. The Brazilian literature has highlighted that environmental
      factors (religiosity, working conditions, and substance use among family and
      friends) and psychosocial factors (such as conflicts with parents and feelings of
      negativeness and loneliness) are associated with the tobacco and alcohol use
      among adolescents. CONCLUSIONS: The results suggest that consumption of alcohol
      and tobacco among adolescents has reached alarming prevalences in various
      localities in Brazil. Since unhealthy behavior tends to continue from adolescence
      into adulthood, public policies aimed towards reducing alcohol and tobacco use
      among Brazilians over the medium and long terms may direct young people and the
      subgroups at higher risk towards such behavior.

PMID- 23128269
TI  - [Evaluation of health literacy and the readability of information leaflets].
AB  - OBJECTIVE: The proper use of information leaflets for medications depends, among
      other factors, on its readability and on users' literacy, i.e. the ability to
      clearly identify letters, words and sentences and the ability to understand and
      use that information. The study purpose was to investigate the possible
      relationship between a measure of functional health literacy and the readability
      of a leaflet for a non-steroidal anti-inflammatory medicine, the later assessed
      by the appropriate European guideline. In a sample of 53 urban participants,
      recruited in 2010 from a pharmacy in Lisboa (Portugal) and with varying literacy,
      statistical analysis found no relationship between the level of literacy and the
      various parameters to assess the quality and readability of an information
      leaflet.

PMID- 23128270
TI  - [Intake recommendations and labeling of trans fat in processed foods in Brazil:
      analysis of official documents].
AB  - Consumption of trans fat has been proven to be harmful to human health. This
      lipid is found mainly in partially hydrogenated vegetable fat, which is widely
      used in processed foods. The aim of this study was to analyze official
      publications on maximum limits for consumption of trans fat and the regulations
      for its mandatory notification on the nutritional labeling of processed foods in
      Brazil. Weaknesses in the content of the documents analyzed were found,
      especially regarding the need for reformulation of both the maximum recommended
      consumption and the notification of trans fat on nutritional labeling for
      processed foods. This paper makes suggestions for this reformulation, through
      which it is sought to help consumers in controlling their trans fat intake and,
      consequently, in promotion of health.

PMID- 23128271
TI  - Evaluation of commercial kits for extraction of DNA and RNA from Clostridium
      difficile.
AB  - Commercial nucleic acid extraction kits are a cost effective, efficient and
      convenient way to isolate DNA and RNA from bacteria. Despite the increasing
      importance of the gastrointestinal pathogen, Clostridium difficile, and the
      increased use of nucleic acids in its identification, characterization, and
      investigation of virulence factors, no standardized or recommended methods for
      nucleic acid isolation exist. Here, we sought to evaluate 4 commercial DNA
      extraction kits and 3 commercial RNA extraction kits assessing cost, labor
      intensity, purity, quantity and quality of nucleic acid preparations. The DNA
      extraction kits produced a range of concentrations (20.9-546 ng/ml) and
      A(260/280) ratios (1.92-2.11). All kits were suitable for DNA extraction with the
      exception of the Roche MagNA pure LC DNA isolation kit III which produced DNA of
      high yield but with substantial shearing, but that did not affect downstream PCR
      amplifications. For RNA extraction, the Qiagen RNeasy mini kit stood out
      producing preparations of consistently higher concentrations and higher RNA
      integrity numbers (RIN). The Roche MagNA pure LC RNA isolation kit produced
      preparations that could not be properly assigned RINs due to a failure to remove
      small RNAs which were interpreted as degradation. Good DNA and RNA yield are
      critical but methods are often overlooked. This study highlights the potential
      for critical variation between established commercial systems and the need for
      assessment of any extraction methods that are used.

PMID- 23128272
TI  - Interfacial toughening of solution processed Ag nanoparticle thin films by
      organic residuals.
AB  - Reliable integration of solution processed nanoparticle thin films for next
      generation low-cost flexible electronics is limited by mechanical damage in the
      form of delamination and cracking of the films, which has not been investigated
      quantitatively or systematically. Here, we directly measured the interfacial
      fracture energy of silver nanoparticle thin films by using double cantilever beam
      fracture mechanics testing. It was demonstrated that the thermal annealing
      temperature and period affect the interfacial fracture energy. Also it was found
      that the interfacial fracture resistance can be maximized with optimized
      annealing conditions by the formation of organic residual bridges during the
      annealing process.

PMID- 23128273
TI  - Nanoparticle-induced permeability of lipid membranes.
AB  - Monte Carlo simulations using the bond fluctuation method with explicit solvent
      reveal the mechanism of enhanced permeability of lipid bilayers induced by the
      adsorption of nanoparticles with controlled hydrophobicity. Simulation results
      indicate an adsorption transition of nanoparticles on the bilayer in a certain
      range of relative degree of hydrophobicity. In this range the nanoparticles can
      translocate through the bilayer, reversibly destabilizing the structure of the
      bilayer and inducing enhanced permeability for water and small solutes. This
      transition is broader for amphiphilic nanoparticles.

PMID- 23128274
TI  - Comparative analysis of hyaluronan's affinity for antivascular endothelial growth
      factor agents.
AB  - BACKGROUND: Differences in the efficacy of bevacizumab, an antivascular
      endothelial growth factor (VEGF) agent, against retinopathy with
      neovascularization when injected into the vitreous cavity of vitrectomized and
      nonvitrectomized eyes suggests the involvement of hyaluronan, a major component
      of the vitreous body. This study aimed to compare the affinities of hyaluronan
      for anti-VEGF agents in vitro. METHODS: We examined the affinities of hyaluronan
      for 3 anti-VEGF agents (bevacizumab, pegaptanib and ranibizumab). Tritium [(3)H]
      labeled hyaluronan was incubated separately with each anti-VEGF agent. The ratio
      of bound and unbound hyaluronan measured using solid and liquid phase methods was
      calculated. RESULTS: Hyaluronan demonstrated a significantly greater affinity for
      bevacizumab than for pegaptanib or ranibizumab. CONCLUSIONS: The absence or
      presence of hyaluronan may be associated with the clinical efficacy of
      bevacizumab injected into the vitreous cavity due to the affinity of hyaluronan
      for bevacizumab.

PMID- 23128276
TI  - Health system loath to innovate, experts say.

PMID- 23128277
TI  - Temporomandibular disorders.

PMID- 23128278
TI  - Reining in public spending on health care.

PMID- 23128279
TI  - Recent crime legislation and the challenge for prison health care.

PMID- 23128280
TI  - Person-first language: Noble intent but to what effect?

PMID- 23128281
TI  - Successful aging: is there hope?

PMID- 23128282
TI  - What next for MDGs?

PMID- 23128284
TI  - Peripheral edema with pregabalin.

PMID- 23128283
TI  - Home blood pressure monitoring with nurse-led telephone support among patients
      with hypertension and a history of stroke: a community-based randomized
      controlled trial.
AB  - BACKGROUND: Adequate control of blood pressure reduces the risk of recurrent
      stroke. We conducted a randomized controlled study to determine whether home
      blood pressure monitoring with nurse-led telephone support would reduce blood
      pressure in patients with hypertension and a history of stroke. METHODS: We
      recruited 381 participants (mean age 72 years) from outpatient and inpatient
      stroke clinics between Mar. 1, 2007, and Aug. 31, 2009. Nearly half (45%, 170) of
      the participants had some disability due to stroke. Participants were visited at
      home for a baseline assessment and randomly allocated to home blood pressure
      monitoring (n = 187) or usual care (n = 194). Those in the intervention group
      were given a monitor, brief training and telephone support. Participants who had
      home blood pressure readings consistently over target (target < 130/80 mm Hg)
      were advised to consult their family physician. The main outcome measure was a
      fall in systolic blood pressure after 12 months, measured by an independent
      researcher unaware of group allocation. RESULTS: Despite more patients in the
      intervention group than in the control group having changes to antihypertensive
      treatment during the trial period (60.1% [98/163] v. 47.6% [78/164], p = 0.02),
      the fall in systolic blood pressure from baseline did not differ significantly
      between the groups (adjusted mean difference 0.3 mm Hg, 95% confidence interval 
      3.6 to 4.2 mm Hg). Subgroup analysis showed significant interaction with
      disability due to stroke (p = 0.03 at 6 months) and baseline blood pressure (p =
      0.03 at 12 months). INTERPRETATION: Overall, home monitoring did not improve
      blood pressure control in patients with hypertension and a history of stroke. It
      was associated with a fall in systolic pressure in patients who had uncontrolled
      blood pressure at baseline and those without disability due to stroke. TRIAL
      REGISTRATION: ClinicalTrials.gov registration NCT00514800.

PMID- 23128287
TI  - Reframe the health debate, minister urges.

PMID- 23128285
TI  - Levels of 25-hydroxyvitamin D in familial longevity: the Leiden Longevity Study.
AB  - BACKGROUND: Low levels of 25(OH) vitamin D are associated with various age
      related diseases and mortality, but causality has not been determined. We
      investigated vitamin D levels in the offspring of nonagenarians who had at least
      one nonagenarian sibling; these offspring have a lower prevalence of age-related
      diseases and a higher propensity to reach old age compared with their partners.
      METHODS: We assessed anthropometric characteristics, 25(OH) vitamin D levels,
      parathyroid hormone levels, dietary vitamin D intake and single nucleotide
      polymorphisms (SNPs) associated with vitamin D levels. We included offspring (n =
      1038) of nonagenarians who had at least one nonagenarian sibling, and the
      offsprings' partners (n = 461; controls) from the Leiden Longevity Study. We
      included age, sex, body mass index, month during which blood sampling was
      performed, dietary and supplemental vitamin D intake, and creatinine levels as
      possible confounding factors. RESULTS: The offspring had significantly lower
      levels of vitamin D (64.3 nmol/L) compared with controls (68.4 nmol/L; p =
      0.002), independent of possible confounding factors. There was no difference in
      the levels of parathyroid hormone between groups. Compared with controls, the
      offspring had a lower frequency of a genetic variant in the CYP2R1 gene
      (rs2060793) (p = 0.04). The difference in vitamin D levels between offspring and
      controls persisted over the 2 most prevalent genotypes of this SNP.
      INTERPRETATION: Compared with controls, the offspring of nonagenarians who had at
      least one nonagenarian sibling had a reduced frequency of a common variant in the
      CYP2R1 gene, which predisposes people to high vitamin D levels; they also had
      lower levels of vitamin D that persisted over the 2 most prevalent genotypes.
      These results cast doubt on the causal nature of previously reported associations
      between low levels of vitamin D and age-related diseases and mortality.

PMID- 23128288
TI  - Racemic marinopyrrole B by total synthesis.
AB  - The first synthesis of marinopyrrole B, which is highly active against
      methicillin-resistant Staphylococcus aureus, is described. The route involved
      constructing a pyrrole ring on the nitrogen of a 3-bromo-4,5-dichloropyrrole by N
      alkylation with a special Michael acceptor having an allylic leaving group; the
      second pyrrole ring was then formed by a Paal-Knorr reaction.

PMID- 23128289
TI  - Molecular detection of HPV and Chlamydia trachomatis infections in Brazilian
      women with abnormal cervical cytology.
AB  - The question of whether Chlamydia trachomatis (Ct) is a cofactor for human
      Papillomavirus (HPV) in cervical carcinogenesis is still controversial. We
      conducted a molecular detection study of both infections in 622 Brazilian women,
      including 252 women with different grades of abnormal cervical cytology and
      cervical cancer (CC; cases) and 370 women with normal cytology (controls).
      Although Ct infection did not seem related to CC carcinogenicity, women with
      abnormal cytology had a significant high rate of Ct infection. Therefore, it is
      important to adopt protocols for diagnosis and treatment of this bacterium in
      conjunction with screening for CC in this population.

PMID- 23128290
TI  - Relationship between use of water from community-scale water treatment refill
      kiosks and childhood diarrhea in Jakarta.
AB  - In developing countries, safe piped drinking water is generally unavailable, and
      bottled water is unaffordable for most people. Purchasing drinking water from
      community-scale decentralized water treatment and refill kiosks (referred to as
      isi ulang depots in Indonesia) is becoming a common alternative. This study
      investigates the association between diarrhea risk and community-scale water
      treatment and refill kiosk. We monitored daily diarrhea status and water source
      for 1,000 children 1-4 years of age in Jakarta, Indonesia, for up to 5 months.
      Among children in an urban slum, rate of diarrhea/1,000 child-days varied
      significantly by primary water source: 8.13 for tap water, 3.60 for bottled
      water, and 3.97 for water kiosks. In multivariable Poisson regression analysis,
      diarrhea risk remained significantly lower among water kiosk users (adjusted rate
      ratio [RR] = 0.49, 95% confidence interval [CI] = 0.29-0.83) and bottled water
      users (adjusted RR = 0.45, 95% CI = 0.21-0.97), compared with tap water users. In
      a peri-urban area, where few people purchased from water kiosk (N = 28, 6% of
      total population), diarrhea rates were lower overall: 2.44 for well water, 1.90
      for bottled water, and 2.54 for water kiosks. There were no significant
      differences in diarrhea risk for water kiosk users or bottled water users
      compared with well water users. Purchasing water from low-cost water kiosks is
      associated with a reduction in diarrhea risk similar to that found for bottled
      water.

PMID- 23128291
TI  - Higher risk of infection with dengue at the weekend among male Singaporeans.
AB  - A growing body of evidence suggests that dengue infection in Singapore
      predominantly occurs away from the home, but when and where dengue transmission
      occurs is unclear, confounding control efforts. The authors estimate days of the
      week in which dengue inpatients in Singapore were infected during the period 2006
      2008, based on the day they became febrile and historical data on the incubation
      period, using Bayesian statistical methods. Among male inpatients, the relative
      risk of infection is an estimated 57% higher at the weekend, suggesting
      infections associated with the home or leisure activities. There was no evidence
      of elevated risk of infection at the weekend for female inpatients. The study
      motivates further research identifying locales frequented in the week leading up
      to onset to improve the effective targeting of vector control efforts.

PMID- 23128292
TI  - Tuberculosis and histoplasmosis co-infection in AIDS patients.
AB  - Abstract. Coinfection with tuberculosis in some countries occurs in 8-15% of
      human immunodeficiency virus (HIV) -infected patients who have histoplasmosis.
      This coinfection interferes with prompt diagnosis, and treatment is difficult
      because of drug interactions. We retrospectively reviewed the cases of 14 HIV
      infected patients who had concomitant tuberculosis and histoplasmosis. The most
      frequent clinical manifestations were weight loss (85.7%), asthenia (78.5%), and
      fever (64.2%). The diagnosis of histoplasmosis was made primarily by
      histopathology (71.4%), and the diagnosis of tuberculosis was made by means of
      direct microscopic examination (71.4%). Death occurred in two patients, and
      relapse of both infections occurred in one patient. Moxifloxacin was substituted
      for rifampicin in six patients, with good outcomes noted for both infections. The
      clinical presentation does not readily identify acquired immunodeficiency
      syndrome (AIDS) patients who have tuberculosis and histoplasmosis. The use of a
      fluoroquinolone as an alternative agent in place of rifampicin for tuberculosis
      allows effective therapy with itraconazole for histoplasmosis.

PMID- 23128293
TI  - Surveillance and molecular characterization of group A rotaviruses in Goroka,
      Papua New Guinea.
AB  - In this study, we investigated the molecular epidemiology of group A rotaviruses
      in cases of acute gastroenteritis in Goroka, Papua New Guinea. From April 2008
      through November 2010, 813 diarrheal stool samples were collected from children <
      5 years of age hospitalized with acute gastroenteritis. Rotavirus antigen was
      detected in 31.2% of samples using a commercial enzyme-linked immunosorbent
      assay. Genotyping revealed the presence of the globally circulating strains
      G1P[8] (50.0%), G3P[8] (23.0%), and G2P[4] (8.2%). The globally emerging strains
      G9 and G12 were detected in 1.2% and 6.1% of samples, respectively. Mixed
      infections were detected in a high proportion of samples (11.9%), with 9.0% and
      3.7% of samples displaying multiple G and P genotypes, respectively.

PMID- 23128294
TI  - Marked age-dependent prevalence of symptomatic and patent infections and
      complexity of distribution of human Plasmodium species in central Vietnam.
AB  - In Vietnam, Plasmodium falciparum and P. vivax are responsible for most malaria
      infections, and P. malariae and P. ovale infections are rarely reported.
      Nevertheless, species-specific polymerase chain reaction analysis on 2,303 blood
      samples collected during a cross-sectional survey conducted in a forest area of
      central Vietnam identified 223 (9.7%) P. falciparum, 170 (7.4%) P. vivax, 95
      (4.1%) P. malariae, and 19 (0.8%) P. ovale mono-infections and 164 (7.1%) mixed
      infections. Of the 671 Plasmodium-positive samples by polymerase chain reaction,
      only 331 were detected by microscopy. Microscopy poorly diagnosed P. malariae, P.
      ovale, and mixed infections. Clinical and sub-clinical infections occurred in all
      age groups. The risk for infection and disease decreased with age, probably
      because of acquired partial immunity. The common occurrence of sub-patent
      infections seems to indicate that the malaria burden is underestimated and that
      diagnostic and therapeutic policies should be adapted accordingly.

PMID- 23128295
TI  - Mosquito-producing containers, spatial distribution, and relationship between
      Aedes aegypti population indices on the southern boundary of its distribution in
      South America (Salto, Uruguay).
AB  - A study was conducted in the city of Salto, Uruguay, to identify mosquito
      producing containers, the spatial distribution of mosquitoes and the relationship
      between the different population indices of Aedes aegypti. On each of 312
      premises visited, water-filled containers and immature Ae. aegypti mosquitoes
      were identified. The containers were counted and classified into six categories.
      Pupae per person and Stegomyia indices were calculated. Pupae per person were
      represented spatially. The number of each type of container and number of
      mosquitoes in each were analyzed and compared, and their spatial distribution was
      analyzed. No significant differences in the number of the different types of
      containers with mosquitoes or in the number of mosquitoes in each were found. The
      distribution of the containers with mosquito was random and the distribution of
      mosquitoes by type of container was aggregated or highly aggregated.

PMID- 23128296
TI  - Mechanical stimulation of chondrocyte-agarose hydrogels.
AB  - Articular cartilage suffers from a limited repair capacity when damaged by
      mechanical insult or degraded by disease, such as osteoarthritis. To remedy this
      deficiency, several medical interventions have been developed. One such method is
      to resurface the damaged area with tissue-engineered cartilage; however, the
      engineered tissue typically lacks the biochemical properties and durability of
      native cartilage, questioning its long-term survivability. This limits the
      application of cartilage tissue engineering to the repair of small focal defects,
      relying on the surrounding tissue to protect the implanted material. To improve
      the properties of the developed tissue, mechanical stimulation is a popular
      method utilized to enhance the synthesis of cartilaginous extracellular matrix as
      well as the resultant mechanical properties of the engineered tissue. Mechanical
      stimulation applies forces to the tissue constructs analogous to those
      experienced in vivo. This is based on the premise that the mechanical
      environment, in part, regulates the development and maintenance of native
      tissue(1,2). The most commonly applied form of mechanical stimulation in
      cartilage tissue engineering is dynamic compression at physiologic strains of
      approximately 5-20% at a frequency of 1 Hz(1,3). Several studies have
      investigated the effects of dynamic compression and have shown it to have a
      positive effect on chondrocyte metabolism and biosynthesis, ultimately affecting
      the functional properties of the developed tissue(4-8). In this paper, we
      illustrate the method to mechanically stimulate chondrocyte-agarose hydrogel
      constructs under dynamic compression and analyze changes in biosynthesis through
      biochemical and radioisotope assays. This method can also be readily modified to
      assess any potentially induced changes in cellular response as a result of
      mechanical stimuli.

PMID- 23128297
TI  - Identification of glycosyltransferases involved in cell wall synthesis of wheat
      endosperm.
AB  - Plant cell walls are complex structures critical for plant fitness and valuable
      for human nutrition as dietary fiber and for industrial uses such as biofuel
      production. The cell wall polysaccharides in wheat endosperm consist of two major
      polymers, arabinoxylans and beta-glucans, as well as other minor components. Most
      of these polysaccharides are synthesized in the Golgi apparatus but the
      mechanisms underlying their synthesis have yet to be fully elucidated and only a
      few of the enzymes involved have been characterized. To identify actors involved
      in the wheat endosperm cell wall formation, we used a subcellular fractionation
      strategy to isolate Golgi-enriched fractions from endosperm harvested during
      active cell wall deposition. The proteins extracted from these Golgi-enriched
      fractions were analyzed by LC-MS/MS. We report the identification of 1135
      proteins among which 64 glycosyltransferases distributed in 17 families. Their
      potential function in cell wall synthesis is discussed. In addition, we
      identified 63 glycosylhydrolases, some of which may be involved in cell wall
      remodeling. Several glycosyltransferases were validated by showing that when
      expressed as fusion proteins with a fluorescent reporter, they indeed accumulate
      in the Golgi apparatus. Our results provide new candidates potentially involved
      in cell wall biogenesis in wheat endosperm.

PMID- 23128298
TI  - Differential proteomic analysis of Aspergillus fumigatus morphotypes reveals
      putative drug targets.
AB  - Aspergillus fumigatus is the main etiological agent of invasive aspergillosis, an
      important opportunistic infection for neutropenic patients. The main risk groups
      are patients with acute leukemia and bone marrow transplantation recipients. The
      lack of an early diagnostic test together with the limited spectrum of antifungal
      drugs remains a setback to the successful treatment of this disease. During
      invasive infection the inhaled fungal conidia enter the morphogenic cycle leading
      to angioinvasive hyphae. This work aimed to study differentially expressed
      proteins of A. fumigatus during morphogenesis. To achieve this goal, a 2D-DIGE
      approach was applied to study surface proteins extractable by reducing agents of
      two A. fumigatus morphotypes: germlings and hyphae. Sixty-three differentially
      expressed proteins were identified by MALDI-ToF/MS. We observed that proteins
      associated with biosynthetic pathways and proteins with multiple functions
      (miscellaneous) were over-expressed in the early stages of germination, while in
      hyphae, the most abundant proteins detected were related to metabolic processes
      or have unknown functions. Among the most interesting proteins regulated during
      morphogenesis, two putative drug targets were identified, the translational
      factor, eEF3 and the CipC-like protein. Neither of these proteins are present in
      mammalian cells.

PMID- 23128299
TI  - Development of an activated carbon-packed microbial bioelectrochemical system for
      azo dye degradation.
AB  - A microbial bioelectrochemical reactor (BER) was employed for the degradation of
      azo dyes without the use of an external electron donor, using activated carbon
      (GAC) as a redox mediator. Contribution of pH values, open circuit potential
      (OCP), dye concentration and applied current were individually studied. A batch
      system and an upflow fixed bed bioreactor were built for analyzing the effect of
      the applied current on biodegradation of the azo dye Reactive Red 272. The
      presence of GAC (20% w/v) regulated both pH and OCP values in solution and led to
      a removal efficiency of 98%. Cyclic voltammetry results indicate a dependence of
      the electron transfer mechanism with the concentration of the azo compound. With
      these results, a continuous flow reactor operating with J=0.045 mA cm(-2), led to
      removal rates of 95% (+/- 3.5%) in a half-residence time of 1 hour.

PMID- 23128300
TI  - The effect of mental ill health on absence from work in different occupational
      classifications: analysis of routine data in the British Household Panel Survey.
AB  - OBJECTIVE: To investigate relationship of mental ill health to absence from work
      in different occupational classifications. METHOD: Examined sickness absence,
      mental health (GHQ-12), physical health, job characteristics, and personal
      characteristics in 18 waves of the British Household Panel Survey. RESULTS:
      Overall sickness absence rate was 1.68%. Increased absence was associated with
      age greater than 45 years, female gender, lower occupational classification, and
      public-sector employers. Decreased absence was associated with part-time working.
      Scoring 4 or more on the General Health Questionnaire 12-item version (GHQ-12
      caseness) was strongly associated with sickness absence. Public-sector employers
      had highest rates of sickness absence. GHQ-12 caseness had largest impact on
      absence in the public and nonprofit sectors, whereas physical health problems
      impacted more in the private sector. CONCLUSIONS: GHQ-12 caseness is strongly
      associated with increased absence in all classifications of occupations.
      Differences between sectors require further investigation.

PMID- 23128301
TI  - Prospective evaluation of duodenogastroesophageal reflux in gastroesophageal
      reflux disease patients refractory to proton pump inhibitor therapy.
AB  - BACKGROUND: Duodenogastroesophageal reflux (DGER) is considered an independent
      risk factor for complicated reflux disease (gastroesophageal reflux disease;
      GERD). However, the role of DGER in GERD patients refractory to proton pump
      inhibitors (PPI) remains poorly understood. METHODS: 85 patients with clinical
      reflux symptoms and a history of ineffective response to PPIs were enrolled in
      the study. Patients with elevated reflux measurement (pH and/or Bilitec
      measurement; n = 47) received pantoprazole 80 mg for 8 weeks. Clinical outcome
      was defined as response (<=2 symptoms/week) or nonresponse (>=3 symptoms/week).
      RESULTS: Of the 47 patients with elevated reflux measurement, 30 were classified
      as responders and 17 as nonresponders. Treatment with pantoprazole resulted in a
      significant reduction of acidic reflux in both PPI responders and PPI
      nonresponders. In contrast, DGER was only significantly reduced in the PPI
      responder group (22.8 +/- 22.8 vs. 6.6 +/- 10.8%; p < 0.05) but not in the PPI
      nonresponder group (24.5 +/- 18.6 vs. 22.2 +/- 12.7%; p > 0.05). CONCLUSIONS: The
      presented study firstly describes that nonresponsiveness to PPI is associated
      with a limited effect of PPIs on reducing DGER. Thus, persistent DGER may play a
      key role in mediating reflux symptoms refractory to high-dose PPIs.

PMID- 23128303
TI  - Aging-related changes in blood-brain barrier integrity and the effect of dietary
      fat.
AB  - BACKGROUND: Disturbances in blood-brain barrier (BBB) integrity contribute to the
      onset and progression of neurodegenerative diseases including Alzheimer's disease
      (AD) and vascular dementia (VaD). Aging is positively associated with AD and VaD
      risk, but this may reflect comorbidities or the effects of other chronic
      modulators of vascular function such as diet. OBJECTIVE: To explore putative
      synergistic effects of aging with diet, in this study genetically unmanipulated
      mice were maintained on diets enriched in saturated fatty acids (SFA) or
      cholesterol and compared to mice provided with low-fat (LF) feed formula.
      METHODS: The functional integrity of the BBB was assessed following 3, 6 and 12
      months of dietary intervention commenced at 6 weeks of age, by determining the
      brain parenchymal extravasation of immunoglobulin G (IgG). RESULTS: Mice
      maintained on the SFA- or cholesterol-enriched diet showed significant
      parenchymal IgG abundance following 3 months of feeding, concomitant with
      diminished expression of the tight junction protein occludin. LF control mice had
      essentially no evidence of BBB disturbances. Six months of SFA feeding
      exacerbated the difference in IgG abundance compared to the LF mice. At 12 months
      of feeding, the control LF mice also had significant parenchymal IgG that was
      comparable to mice fed the SFA- or cholesterol-enriched diet for 3 months.
      However, there may have been an adaptation to the fat-enriched diets because SFA
      and cholesterol did not exacerbate IgG parenchymal accumulation beyond 6 months
      of feeding. CONCLUSION: Collectively, the study suggests that diets enriched in
      SFA or cholesterol accelerate the onset of BBB dysfunction that otherwise occurs
      with aging.

PMID- 23128302
TI  - Low blood levels of long-chain n-3 polyunsaturated fatty acids in US hemodialysis
      patients: clinical implications.
AB  - BACKGROUND: Cardioprotective and other clinical benefits of long-chain n-3
      polyunsaturated fatty acids (PUFA) are inversely related to dietary intake and
      hence blood content. We therefore investigated, in the first study of its kind,
      the blood content and distribution of these fatty acids in a large representative
      population of US hemodialysis patients. METHODS: Frozen sera were obtained from
      400 individuals who were part of a large, contemporary, representative cohort of
      US incident hemodialysis patients. Long-chain n-3 PUFA were measured in total
      serum lipids and in the neutral and polar serum fractions using gas
      chromatography and solid phase extraction techniques. Mean long-chain n-3 PUFA
      levels were compared to levels in other dialysis and nondialysis populations from
      published reports. RESULTS: The study population was qualitatively similar to the
      overall US hemodialysis population in terms of major clinical characteristics.
      Long-chain n-3 PUFA were present in the serum polar fraction, with essentially
      none being detected in the neutral fraction (p < 0.0001 for polar vs. neutral
      fractions for all three long-chain n-3 PUFA). Mean serum long-chain n-3 PUFA
      levels (weight percent (+/-SD): total 1.55 +/- 0.95, polar 3.99 +/- 1.45) were
      low compared to nondialysis and most other non-US hemodialysis cohorts.
      CONCLUSIONS: While US hemodialysis patients have a blood distribution of long
      chain n-3 PUFA that is similar to that in the general population, blood content
      is among the lowest recorded in the medical literature. This has implications for
      renal dietary recommendations and makes US patients an ideal group for testing
      the clinical effects of long-chain n-3 PUFA supplementation.

PMID- 23128308
TI  - Picture of the month: disseminated gonococcus infection.

PMID- 23128309
TI  - Advice for patients: reading to children.

PMID- 23128310
TI  - Effects of restructured pork containing Himanthalia elongata on adipose tissue
      lipogenic and lipolytic enzyme expression of normo- and hypercholesterolemic
      rats.
AB  - BACKGROUND: Inclusion of seaweeds in restructured pork (RP) would improve meat
      health properties. AIM: The aim was to determine the effects of RP containing
      Himanthalia elongata on growth, organ weight, cholesterolemia, and expression of
      lipoprotein lipase (LPL), acetyl CoA carboxylase (ACC), fatty acid synthase
      (FAS), and hormone-sensitive lipase (HSL) in adipose tissue of Wistar rats.
      METHODS: The control group (C) consumed control RP, and the seaweed group (SS)
      consumed RP with 5% Himanthalia elongata. Animals on cholesterol-enriched diets
      (CholC, CholSS) consumed their corresponding basal diets with supplementary
      cholesterol (2.43%) plus cholic acid (0.49%) as hypercholesterolemic agents.
      RESULTS: Seaweed inclusion did not modify cholesterolemia but reduced (p < 0.01)
      the hypercholesterolemic effect of dietary cholesterol plus cholic acid. CholC
      rats presented lower (p < 0.05) adipose fat and weight than C rats. Cholesterol
      feeding affected HSL, ACC, and FAS expression (p < 0.05), while alga consumption
      influenced HSL and ACC (p < 0.05). LPL was not significantly affected by both
      factors. CholSS rats showed decreased HSL and FAS (p < 0.05) but increased ACC (p
      < 0.05) expression compared with CholC rats. CONCLUSION: Himanthalia RP partially
      blocked the dietary hypercholesterolemic effect and changed the
      lipogenic/lipolytic enzyme expression, reducing the wasting effect of
      hypercholesterolemia on adipose tissue in rats.

PMID- 23128311
TI  - Nanocomposite catalysts producing durable, super-black carbon nanotube systems:
      applications in solar thermal harvesting.
AB  - A novel two-step approach for preparing carbon nanotube (CNT) systems, exhibiting
      an extraordinary combination of functional properties, is presented. It is based
      upon nanocomposite films consisting of metal (Me = Ni, Fe, Mo, Sn) nanoparticles
      embedded into diamond-like carbon (DLC). The main concept behind this approach is
      that DLC inhibits the growth of Me, resulting in the formation of small
      nanospheres instead of layers or extended grains. In the second step, DLC:Me
      substrates were used as catalyst templates for the growth of CNTs by the thermal
      chemical vapor deposition (T-CVD) process. X-ray photoelectron spectroscopy (XPS)
      has shown that at the T-CVD temperature of 700  degrees C DLC is completely
      graphitized and NiC is formed, making DLC:Ni a very effective catalyst for CNT
      growth. The catalyst layers and the CNT systems have been characterized with a
      wide range of analytical techniques such as Auger electron spectroscopy and X-ray
      photoelectron spectroscopy (AES/XPS), X-ray diffraction, reflectivity and
      scattering, Raman spectroscopy, scanning electron microscopy, atomic force
      microscopy, and optical and electrical testing. The produced CNTs are of
      excellent quality, without needing any further purification, durable, firmly
      attached to the substrate, and of varying morphology depending on the density of
      catalyst nanoparticles. The produced CNTs exhibit exceptional properties, such as
      super-hydrophobic surfaces (contact angle up to 165 degrees ) and exceptionally
      low optical reflection (reflectivity <10(-4)) in the entirety of the visible
      range. The combination of the functional properties makes these CNT systems
      promising candidates for solar thermal harvesting, as it is demonstrated by solar
      simulation experiments.

PMID- 23128313
TI  - [More international RESP].

PMID- 23128312
TI  - Anti-inflammatory effects of egg white combined with chalcanthite in
      lipopolysaccharide-stimulated BV2 microglia through the inhibition of NF-kappaB,
      MAPK and PI3K/Akt signaling pathways.
AB  - Egg white-chalcanthite (EWCC) is a mixture of egg white and chalcanthite prepared
      by roasting chalcanthite (which is a natural mineral mainly composed of
      CuSO4*5H2O) to the point of dehydration, pulverizing the dehydrated chalcanthite
      and then mixing the pulverized chalcanthite to react with egg white to trigger a
      reaction. When egg white-chalcanthite is prepared in this manner, the toxicity of
      chalcanthite is neutralized by the egg white, so that the toxicity is reduced or
      removed and the pharmaceutical properties are increased. However, the cellular
      and molecular mechanisms underlying the pharmacological activity of EWCC remain
      poorly understood. In this study, we investigated the inhibitory effects of EWCC
      on the production of lipopolysaccharide (LPS)-induced pro-inflammatory mediators
      in BV2 microglia. Our data indicated that the EWCC treatment significantly
      inhibited the excessive production of nitric oxide and prostaglandin E2 in LPS
      stimulated BV2 microglia in a concentration-dependent manner without causing
      cytotoxicity. It also attenuated the expression of inducible nitric oxide
      synthase, cyclooxygenase-2 and pro-inflammatory cytokines, including interleukin
      1beta and tumor necrosis factor-alpha. Moreover, EWCC exhibited anti-inflammatory
      properties by the suppression of nuclear factor-kappaB (NF-kappaB) activation by
      blocking IkappaB-alpha degradation, downregulation of extracellular signal
      regulated kinase, c-Jun N-terminal kinase, p38 mitogen-activated protein kinase
      (MAPK) and phosphoinositide 3-kinase (PI3K)/Akt pathways. Our results indicate
      that the inhibitory effects of EWCC on LPS-stimulated inflammatory mediator
      production in BV2 microglia are associated with the suppression of the NF-kappaB,
      MAPK and PI3K/Akt signaling pathways. These findings suggest that EWCC may offer
      a substantial therapeutic potential for the treatment of neurodegenerative
      diseases that are accompanied by microglial activation.

PMID- 23128314
TI  - [Patients who refuse antiretroviral treatment in prison].
AB  - INTRODUCTION: Current studies of HIV+ patients in the prison population have been
      carried out without considering differences that might exist between patients who
      accept retroviral treatment and those who do not. One possible reason for this
      may be the difficulty in gaining access to patients who refuse antiretroviral
      treatment. However, the prison environment makes it possible to locate and study
      this type of patient, who up till now has not been the subject of study. The aim
      of this article is to describe the clinical and psychosocial state of HIV+
      inmates who refuse ARVT and compare this data with patients receiving treatment
      and others for whom treatment has not been indicated. METHODS: Cross-sectional
      study using 585 HIV+ inmates in three prisons in Andalusia from May to June 2004.
      Refusal, acceptance and non-indication of ARVT treatment was the grouping
      variable used. The independent variables were socio-demographic, psychosocial,
      clinical and other variables relating to the prison environment. RESULTS: 16.8%
      of patients refused ARVT, while 56.3% were receiving treatment and another 26.8
      were not indicated for any medication. Amongst the patients that refused ARVT
      there was a greater prevalence of HIV co-infection, higher inprison consumption
      of opiates and methadone treatment, more cases pending and higher rates of
      recidivism. CONCLUSIONS: these results highlight the existence of a group with
      unique characteristics that is accessible thanks to the special conditions within
      the prison environment. It is a group that chooses not to follow therapeutic
      indications and which represents a risk factor not only for its own health, but
      also for the community at large.

PMID- 23128315
TI  - [The sainsbury centre for mental health: forensic mental health services in
      England and wales].
AB  - The Sainsbury Centre for Mental Health (SCMH) is a charity founded in 1985 by
      Gatsby Charitable Foundation. The SCMH works to improve the quality of life for
      people with mental health problems by influencing policy and practice in mental
      health and related services. Working to improve the quality of mental health care
      for people in prison is one of SCMH main work theme. This paper describes some
      epidemiological aspects of mental health situation of prisoners in England and
      Wales and the available forensic facilities to manage this kind of patients in
      prison.

PMID- 23128316
TI  - [Prisos and inmates population in Venezuela].
AB  - Despite the importance of prison issues in Latin America, there is little in the
      way of detailed local studies or recommendations on the subject. This article
      sets out to describe the situation concerning prisons and inmates in Venezuela.
      Data for this study was compiled from documentary sources and visits to a number
      of Venezuelan prisons from 1998 to 2006 as part of the Health Conference of the
      Programa Penitenciario de la Universidad Central de Venezuela, (Central
      University of Venezuela Prison Program). The program's aim was to make
      contributions towards research on the prison environment at national and regional
      levels that might serve as a precedent for further study of the problems and
      issues that exist, and promote and implement possible solutions.

PMID- 23128317
TI  - [Personality disorders in prison: A complex question].

PMID- 23128318
TI  - [Answer to letter "personality disorders in prison"].

PMID- 23128319
TI  - Metal-free hydrogenation catalysis of polycyclic aromatic hydrocarbons.
AB  - The frustrated Lewis pair, B(C(6)F(5))(3)/Ph(2)PC(6)F(5), acts as an efficient
      catalyst for the hydrogenation of the polycyclic hydrocarbons including
      anthracene derivatives, tetracene and tetraphene, at 80  degrees C and 100 atm
      H(2) pressure via a mechanism involving protonation of polyaromatic species
      followed by hydride transfer.

PMID- 23128320
TI  - Mechanical properties of low-density polyethylene filled by graphite
      nanoplatelets.
AB  - The mechanical properties of GNP/LDPE nanocomposites (graphite nanoplatelets/low
      density polyethylene) have been investigated, in order to establish the  effect
      of nanoscale reinforcement within the polymer matrix. Results show that the
      presence of the filler does not involve a change in the microscopic structure of
      the polymer. However, on a macroscopic scale, GNPs limit the mobility of the
      polymer chains, resulting in an increase in stiffness for the final composite.
      Orientation of GNPs within the LDPE matrix is also an important issue that
      affects mechanical properties and it has been evaluated by testing nanocomposites
      made by different manufacturing techniques (compression moulding and blown
      extrusion). The comparison between the experimental data and the Halpin-Tsai
      model shows that the orientation of GNPs due to the extrusion process leads to
      values of tensile modulus higher than that obtained with the randomly oriented
      disposition resulting from the compression moulding technique.

PMID- 23128321
TI  - Prediction of area under the cyclosporine concentration versus time curve in
      children undergoing hematopoietic stem cell transplantation.
AB  - This prospective study aimed to validate a previously developed first-dose
      limited sampling strategy (LSS) to predict the area under the cyclosporine
      concentration-versus-time curve (AUC) and to develop and then validate an LSS to
      predict cyclosporine AUC at steady state. This two-center Canadian study included
      children (ages .4 to 17.2 years) undergoing myeloablative allogeneic
      hematopoietic stem cell transplantation receiving cyclosporine for acute graft
      versus-host disease prophylaxis. There were three cohorts, each incorporating 24
      AUC determinations: first-dose LSS validation, steady-state LSS development, and
      steady-state LSS validation. Patients contributing data to either of the
      development cohorts were excluded from the corresponding validation group.
      Cyclosporine was given every 12 hours as a 2-hour infusion. Cyclosporine AUC was
      determined after administration of the first cyclosporine dose (8 samples) and
      then once weekly (9 samples) until engraftment. Steady-state LSSs were developed
      using stepwise multiple linear regression. An LSS was considered to provide an
      acceptable estimate of AUC if the lower limit of the 95% confidence limit (CL) of
      the intraclass coefficient was .8 or higher and both bias and precision were 15%
      or less. Fifty-three children age .4 to 18 years participated. Cyclosporine
      concentrations drawn up to 4 hours from the start of the infusion correlated most
      strongly with AUC. The previously developed first-dose LSSs and three steady
      state LSSs met criteria for acceptability. The intraclass coefficients of the
      three-point first-dose LSS validation cohort, three-point steady-state LSS
      development cohort, and three-point steady-state LSS validation cohort were .974
      (95% CL: .941 to .988), .984 (95% CL: .965 to .993), and .993 (95% CL: .984 to
      .997), respectively. The three-point first-dose (2, 6, and 8 hours) and steady
      state (2, 2.5, and 8 hours) LSSs are valid measures of cyclosporine AUC after
      intravenous administration over 2 hours. Their use in a prospective evaluation of
      the relationship between cyclosporine AUC and hematopoietic stem cell
      transplantation clinical outcomes in children is suggested.

PMID- 23128323
TI  - Transcription reinitiation by RNA polymerase III.
AB  - The retention of transcription proteins at an actively transcribed gene
      contributes to maintenance of the active transcriptional state and increases the
      rate of subsequent transcription cycles relative to the initial cycle. This
      process, called transcription reinitiation, generates the abundant RNAs in living
      cells. The persistence of stable preinitiation intermediates on activated genes
      representing at least a subset of basal transcription components has long been
      recognized as a shared feature of RNA polymerase (Pol) I, II and III-dependent
      transcription in eukaryotes. Studies of the Pol III transcription machinery and
      its target genes in eukaryotic genomes over the last fifteen years, has uncovered
      multiple details on transcription reinitiation. In addition to the basal
      transcription factors that recruit the polymerase, Pol III itself can be retained
      on the same gene through multiple transcription cycles by a facilitated recycling
      pathway. The molecular bases for facilitated recycling are progressively being
      revealed with advances in structural and functional studies. At the same time,
      progress in our understanding of Pol III transcriptional regulation in response
      to different environmental cues points to the specific mechanism of Pol III
      reinitiation as a key target of signaling pathway regulation of cell growth. This
      article is part of a Special Issue entitled: Transcription by Odd Pols.

PMID- 23128322
TI  - Autologous stem cell transplantation for refractory or poor-risk relapsed
      Hodgkin's lymphoma: effect of the specific high-dose chemotherapy regimen on
      outcome.
AB  - More active high-dose chemotherapy (HDC) regimens are needed for refractory
      Hodgkin's lymphoma (HL). We report a cohort analysis of 180 consecutive patients
      with primary refractory or poor-risk relapsed HL treated with busulfan-melphalan
      (Bu-Mel) (n = 39), gemcitabine-busulfan-melphalan (Gem-Bu-Mel) (n = 84), or BEAM
      (BCNU, etoposide, ara-C, melphalan; n = 57) between 2005 and 2010. Their pre-HDC
      positron emission tomography (PET) scans were interpreted prospectively. Despite
      more prevalent poor-risk features in the Gem-Bu-Mel cohort, such as PET-positive
      tumors at HDC, tumors growing at HDC, extranodal disease, or bulky tumors at
      prior relapse, this cohort had improved outcomes compared with the Bu-Mel and
      BEAM cohorts, with event-free survival (EFS) rates of 57%, 33%, and 39%,
      respectively (P = .01), at median follow-up of the whole population of 36 months
      (range, 3 to 72). Their respective overall survival (OS) rates were,
      respectively, 82%, 52%, and 59% (P = .04). Secondary acute myelogenous leukemia
      was seen in 5 patients after BEAM but was not seen in Gem-Bu-Mel and Bu-Mel
      cohorts (P = .004). Multivariate analyses showed independent adverse effects of
      an HDC regimen different from Gem-Bu-Mel (hazard ratio [HR] for EFS = 2.3, P =
      .0008; HR for OS = 2.7, P = .0005), positive PET at HDC (HR for EFS = 2.2, P =
      .004, HR for OS = 3.1, P = .0001), and >1 previous salvage line (HR for EFS =
      1.9, P = .008, HR for OS = 1.8, P = .07). Gem-Bu-Mel improved outcomes in this
      cohort analysis of patients with refractory/poor-risk relapsed HL and merits
      evaluation in randomized phase III trials.

PMID- 23128325
TI  - Dbp5 - from nuclear export to translation.
AB  - The DEAD-box RNA helicase Dbp5 is an essential and conserved mRNA export factor
      which functions in the ATP dependent remodeling of RNA/protein complexes. As such
      it displaces mRNA bound proteins at the cytoplasmic site of the nuclear pore
      complex. For the regulation of its RNA-dependent ATPase activity during late
      steps of nuclear transport, Dbp5 requires the nucleoporin Nup159 and its
      cofactors Gle1 and IP6. In addition to its role in mRNA export, a second
      important function of Dbp5 was identified in translation termination, where it
      acts together with eRF1 once the translation machinery has reached the stop
      codon. Similar to mRNA export, this function also requires Gle1-IP6, however, the
      counterpart of Nup159 is still missing. Potential other functions of the nucleo
      cytoplasmic protein Dbp5 are discussed as well as its substrate specificity and
      details in its regulatory cycle that are based on recent biochemical and
      structural characterization. This article is part of a Special Issue entitled:
      The Biology of RNA helicases - Modulation for life.

PMID- 23128326
TI  - Does flexibility influence the ability to sit and rise from the floor?
AB  - OBJECTIVE: The purpose of this study was to establish whether flexibility
      influences the ability to sit and rise from the floor. DESIGN: Subjects aged 6-92
      yrs (n = 3927 [2645 men]) performed the Sitting-Rising Test (SRT) and the
      Flexitest on the same laboratory visit. The SRT evaluates components of
      musculoskeletal function by assessing the subject's ability to sit and rise from
      the floor, which was scored from 0 to 5, with 1 point being subtracted from 5 for
      each support used (hand/knee). The subject's final SRT score, varying from 0 to
      10, was obtained by adding the sitting and rising scores. The Flexitest evaluates
      the maximum passive range of motion of 20 body joint movements. For each one of
      the movements, there are five possible scores, 0-4, in a crescent mobility order.
      Adding the results of the 20 movements provides an overall flexibility score
      called the Flexindex (FLX). RESULTS: The SRT score differed when the Flexindex
      results were stratified into quartiles: 6-26, 27-35, 36-44, and 45-77 (P <
      0.001). The SRT and Flexindex scores were moderately and positively associated (r
      = 0.296; P < 0.001). In addition, the subjects with an SRT score of 0 are less
      flexible for all 20 Flexitest movements than those scoring 10 are. CONCLUSIONS:
      Although seemingly simple tasks, the actions of sitting and rising from the floor
      are also partially dependent on flexibility in male and female subjects of a wide
      age range. Future studies should explore the potential benefit of regular
      flexibility exercises for these actions.

PMID- 23128327
TI  - Neuromuscular medicine competency in physical medicine and rehabilitation
      residents: a method of development and assessment.
AB  - This project endeavored to create an educational module including methodology to
      instruct physical medicine and rehabilitation residents in the evaluation and
      appropriate treatment of patients with neuromuscular disorders. It further sought
      to verify acquired competencies in neuromuscular rehabilitation through objective
      evaluation methodology. An American Association of Neuromuscular and
      Electrodiagnostic Medicine board-certified physician with 10 yrs of clinical
      experience in neuromuscular and general rehabilitation trained 19 residents using
      a standardized competency-based module. The residents were trained through
      clinical training, lectures, and review of self-assessment examination concepts
      from the American Academy of Physical Medicine & Rehabilitation syllabus provided
      in the Archives of Physical Medicine and Rehabilitation. After delivery of the
      educational module, knowledge acquisition and skill proficiency were measured in
      (1) completion of neuromuscular history and physical examination satisfactorily,
      (2) diagnosis and ability to design a patient care management plan via chart
      stimulated recall examinations, (3) physician-patient interaction via patient
      surveys, (4) physician-staff interaction via 360-degree global ratings, and (5)
      ability to write a comprehensive patient care report and to document a patient
      care management plan in accordance with Medicare guidelines via written patient
      reports. Assessment tools developed for this program address the basic
      competencies outlined by the Accreditation Council for Graduate Medical
      Education. To test the success of the standardized educational module, data were
      collected on an ongoing basis. The objective measures compared resident self
      assessment examination scores in neuromuscular rehabilitation before and after
      the institution of the comprehensive neuromuscular competency module in the
      residency program. Nineteen (100%) of 19 residents successfully demonstrated
      proficiency in every segment of the evaluation module by the end of the
      postgraduate year 2 inpatient neuromuscular rehabilitation rotation. Furthermore,
      the residents' proficiency, as demonstrated by the evaluation after the
      implementation of the standardized educational module, positively correlated with
      an increase in the residents' self-assessment examination scores in neuromuscular
      rehabilitation compared with the residents' scores before the educational module
      implementation throughout all 3 yrs of training. Resident proficiency in the
      skills and knowledge pertaining to neuromuscular rehabilitation were objectively
      verified after completion of the standardized educational module. Validation of
      the assessment tool is evidenced by the collected data correlating with
      significantly improved self-assessment examination scores, as outlined in the
      "RESULTS" section. In addition, the clinical development tool was validated by
      the residents being individually observed performing history and physical
      examinations and being deemed competent by the American Association of
      Neuromuscular and Electrodiagnostic Medicine board-certified physical medicine
      and rehabilitation physician. The standardized educational module and evaluation
      methodology provide a potential framework for the definition of baseline
      competency in the clinical training area of neuromuscular rehabilitation.

PMID- 23128324
TI  - PICKLE is a CHD subfamily II ATP-dependent chromatin remodeling factor.
AB  - PICKLE plays a critical role in repression of genes that regulate development
      identity in Arabidopsis thaliana. PICKLE codes for a putative ATP-dependent
      chromatin remodeler that exhibits sequence similarity to members of subfamily II
      of animal CHD remodelers, which includes remodelers such as CHD3/Mi-2 that also
      restrict expression of developmental regulators. Whereas animal CHD3 remodelers
      are a component of the Mi-2/NuRD complex that promotes histone deacetylation,
      PICKLE promotes trimethylation of histone H3 lysine 27 suggesting that it acts
      via a distinct epigenetic pathway. Here, we examine whether PICKLE is also a
      member of a multisubunit complex and characterize the biochemical properties of
      recombinant PICKLE protein. Phylogenetic analysis indicates that PICKLE-related
      proteins in plants share a common ancestor with members of subfamily II of animal
      CHD remodelers. Biochemical characterization of PICKLE in planta, however,
      reveals that PICKLE primarily exists as a monomer. Recombinant PICKLE protein is
      an ATPase that is stimulated by ssDNA and mononucleosomes and binds to both naked
      DNA and mononucleosomes. Furthermore, recombinant PICKLE exhibits ATP-dependent
      chromatin remodeling activity. These studies demonstrate that subfamily II CHD
      proteins in plants, such as PICKLE, retain ATP-dependent chromatin remodeling
      activity but act through a mechanism that does not involve the ubiquitous Mi
      2/NuRD complex.

PMID- 23128328
TI  - Average versus highest intraocular pressure analyses in glaucoma clinical trials.
AB  - PURPOSE: To evaluate methods which account for both eyes as a single, independent
      variable in glaucoma clinical trials. METHODS: A review of clinical trial
      articles published between January 1995 and April 2011 evaluating currently used
      topical glaucoma medications. RESULTS: This analysis included 17 articles with 36
      treatment arms of which 14 were prostaglandins, 13 beta-blockers, 6 topical
      carbonic anhydrase inhibitors and 3 alpha-agonists. Twenty-four articles used
      average intraocular pressure (IOP) analysis, 12 used the highest IOP analysis and
      none utilized the randomized eye method. At untreated baseline, there was a
      difference in the IOP between average IOP and highest baseline IOP analyses at 8
      a.m. (p = 0.001) and for the diurnal curve (p = 0.02) as well as specifically for
      beta-blockers (p = 0.002) at 8 a.m. and beta-blockers for the diurnal curve (p =
      0.01). CONCLUSIONS: This study suggests that the highest IOP analysis method
      generally provides slightly higher IOPs at baseline than the average IOP analysis
      method.

PMID- 23128329
TI  - epsilonGgammaAgammadeltabeta0-thalassemia: a rare but clinically significant
      cause of hemolytic anemia in infants.
AB  - Normal hemoglobin is made of a tetramer of 2 alpha-globin and 2 beta-globin
      polypeptide chains. Deletions in the beta-globin gene cluster can range from a
      few hundred base pairs to loss of the entire cluster resulting in rare, but
      clinically significant, thalassemias. One such entity is
      epsilonGgammaAgammadeltabeta0-thalassemia, a condition that presents within the
      first few weeks of life as a Coombs-negative hemolytic anemia and is not
      identified on routine newborn screening or hemoglobin electrophoresis.

PMID- 23128330
TI  - Young age at diagnosis, male sex, and decreased lean mass are risk factors of
      osteoporosis in long-term survivors of osteosarcoma.
AB  - BACKGROUND: Long-term survival of children with osteosarcoma has increased, but
      most suffer from osteoporosis in adulthood. The aim of this study was to
      investigate the prevalence and identify the risk factors of osteoporosis.
      METHODS: Forty long-term survivors of osteosarcoma and 55 controls were enrolled.
      The mean age of the survivors was 21.8 +/- 5.2 years. They were diagnosed at
      younger than 23 years of age (mean, 14.9 + 5.0 y). Bone mineral densities (BMD)
      and body compositions were measured by dual-energy x-ray absorptiometry. RESULTS:
      Nineteen (47.5%) subjects had osteoporosis and 12 (30.0%) had osteopenia. The
      regions affected by osteoporosis were: femur neck of osteosarcoma site (47.5%),
      unaffected femur neck (12.5%), lumbar spine (12.5%), and total body (15.0%).
      Twelve subjects (30.0%) had 14 episodes of fractures. The identified risk factors
      of osteoporosis were young age at diagnosis, male sex, and low lean mass.
      Subjects diagnosed before attainment of puberty (male <= 16 y, female <= 14 y)
      were found to have a higher prevalence of osteoporosis (37.5% vs. 10.0%, P <
      0.01). Males had a higher prevalence of osteopenia or osteoporosis than females
      (86.4% vs. 66.7%, P < 0.01). Total lean mass was positively correlated with
      unaffected femur neck BMD. Regional lean mass in affected limb was significantly
      reduced along with affected femur neck BMD. CONCLUSIONS: In long-term survivors
      of osteosarcoma, prevalence of osteoporosis and fracture was higher than
      expected. Initial evaluation and regular follow-up of BMD should be performed in
      all osteosarcoma patients, especially in those who did not attain puberty, males,
      and those with a low lean mass.

PMID- 23128331
TI  - Biphasic, hyperdiploid breast tumors in children:  a distinct entity?
AB  - BACKGROUND: The differentiation between a giant fibroadenoma and a phyllodes
      tumor can be a precarious diagnostic task. However, the distinction between the 2
      lesions is important to make, especially since the latter can be malignant and
      consequently the prognoses differ. PROCEDURE: We used various genetic approaches
      to study a breast tumor showing features of both entities in a 10-year-old girl
      with a congenital cerebral malformation and diabetes mellitus. RESULTS:
      Cytogenetic analysis of cultured tumor cells from 3 different samples revealed a
      hyperdiploid karyotype: 50-54,XX,+5,+13,+17,+18,+19,+20,+21. High-resolution
      single nucleotide polymorphism array analysis not only confirmed the trisomies,
      but also revealed uniparental disomy (UPD) for chromosomes 10, 11, and 22. A
      consequence of UPD11 was a homozygous deletion in chromosome band 11p15 affecting
      the PARVA gene; this gene was hemizygously lost in constitutional DNA. Extended
      analysis of the family revealed that the deletion was inherited, but it did not
      segregate with breast tumors or congenital malformations. CONCLUSIONS: Combined
      with the literature data, the findings in the present case strongly suggest that
      biphasic tumors with high hyperdiploid karyotypes constitute a distinct
      clinicomorphologic subgroup of benign breast tumors, being particularly common
      among young children.

PMID- 23128332
TI  - Successful treatment of congenital TTP with a novel approach using plasma-derived
      factor VIII.
AB  - We describe a 19-year-old boy who was diagnosed with congenital thrombotic
      thrombocytopenic purpura (cTTP) at 7 months of age. He was subsequently treated
      with fresh frozen plasma infusions every 3 to 4 weeks for the next 15 years at
      which point he developed significant hypersensitivity reactions to fresh frozen
      plasma. He required immunosuppressive therapy with systemic desensitization in
      the intensive care unit but did not tolerate this regimen and suffered
      debilitating adverse effects. On the basis of the observations from United
      Kingdom, he was started on a trial with Koate, a plasma-derived factor VIII
      concentrate with ADAMTS-13 activity that is commercially available in the United
      States. He tolerated Koate without any complications and attained a target
      platelet count of>100,000/MUL. He has now been in remission for 36 months and
      responds to exacerbations of cTTP with additional doses of Koate. For patients
      with cTTP who are intolerant to plasma infusions, therapy with select plasma
      derived factor concentrates with ADAMTS-13 activity may represent a reasonable
      alternative therapy. 

PMID- 23128333
TI  - Response of pure red cell aplasia to cyclophosphamide after failure of
      mycofenolate mofetil in a patient with polyglandular syndrome type I.
AB  - A 26-year-old female with the classic major and minor components of autoimmune
      polyglandular syndrome type 1 was diagnosed as having pure red cell aplasia.
      Treatment with 1.5 g/d mycofenolate mofetil for 3 months failed to restore
      erythroid production. Treatment with cyclosporine A produced a good partial
      response but led to renal toxicity and was therefore substituted with
      cyclophosphamide, which had a good partial effect and lasted for 18 months. The
      relapse of anemia was not observed during the 6-month follow-up period after the
      cessation of treatment. 

PMID- 23128334
TI  - Notch signaling-related therapeutic strategies with novel drugs in neuroblastoma
      spheroids.
AB  - Neuroblastoma is a severe pediatric tumor characterized by poor prognosis.
      Identification of novel molecular targets and diversion of investigations on new
      drug trials is mandatory for cancer therapy. In this study, vinorelbine tartrate,
      lithium chloride, clomipramine, and medroxyprogesterone acetate are used for the
      possible new treatment modalities in neuroblastoma cells. Notch and c-kit are
      novel molecules in cancer research, and Notch pathway is one of the emerging
      molecules in the neuroblastoma pathogenesis. Cytotoxic effects of these drugs at
      different time points, with different doses were studied in the SH-SY5Y human
      neuroblastoma cell line. Analysis of Notch and c-kit signaling with
      immunohistochemistry were constituted in multicellular tumor spheroids, and
      morphologic investigation was performed for digital imaging of cancer stem cells
      (CSCs) with electron microscopy. Size kinetics of spheroids was also determined
      after drug treatment. Results showed that all drugs were cytotoxic for
      neuroblastoma cells. Yet, this cytotoxic action did not correlate with the
      inhibitory effects in cell signaling. Neuroblastoma spheroids showed increased
      immunoreactivity of Notch signaling and c-kit. Altered ultrastructural CSCs
      morphology was observed after clomipramine and medroxyprogesterone acetate
      treatment compared with other drugs. Lithium chloride showed cellular membrane
      destruction for both CSCs and the remaining population. In this study,
      independent effects of cytotoxicity in tumor cells with respect to CSCs were
      determined. Redundant cells, which are the bulk population in tumor a compound,
      destroyed with therapy, were neither a target for treatment nor a remarkable
      investigation of cancer. 

PMID- 23128335
TI  - Thyroid cancer in pediatric age group:  an institutional experience and review of
      the literature.
AB  - Very few have been reported on children with differentiated thyroid cancer (DTC),
      although 15% of them are diagnosed below 20 years of age. Children with DTC
      present with more advanced disease; however, they have a more favorable outcome.
      In this paper, we aimed to present the data in our institution on pediatric DTC
      patients, making an emphasis on the risk factors of metastasis and recurrence, as
      well as to the outcome of treatment. Clinical data of 50 pediatric patients
      referred to our institution for radioiodine treatment (RAI) between 1976 and 2010
      were obtained. Papillary carcinoma was the most common histopathologic diagnosis
      (36 patients) followed by papillary carcinoma with follicular variant (10
      patients). Multifocality was reported in 66% of the pathology reports. At the
      time of diagnosis 35 patients had regional lymph node metastasis, 18 had local
      invasion, and 11 had distant metastasis. No distant metastasis was present in
      patients with unifocal disease (P=0.018). The mean duration of follow-up was
      77.6+/-62.7 months. Patients with local disease had longer disease-free survival
      than patients with distant metastasis (P=0.033). Despite the small number of
      patients, the follow-up was relatively long and the presented results confirmed
      overall good prognosis in children with DTC.

PMID- 23128336
TI  - Hematological complications of neonatal lupus: case report and review of the
      literature.
AB  - Neonatal thrombocytopenia is a common clinical problem and may be a result of
      maternal and/or fetal conditions. We present a young patient with
      thrombocytopenia as a result of neonatal lupus, a passively acquired autoimmune
      disease. The diagnosis was suspected on the basis of the presence of a facial
      rash. This case highlights the characteristic eruption of neonatal lupus and an
      underappreciated cause of neonatal thrombocytopenia for the pediatric
      hematologist. We also review the hematological complications of neonatal lupus. 

PMID- 23128337
TI  - The Thalassemia center of Antalya State Hospital: 15 years of experience (1994 to
      2008).
AB  - The Thalassemia center of Antalya State Hospital was established in 1994 in
      Antalya, Turkey. The number of newborns with thalassemia decreased statistically
      because of actions taken as a result of prevention studies. A total of 388
      patients, including 246 with thalassemia major (63.4%), 86 with thalassemia
      intermediate (22.1%), 23 with sickle cell+beta-thalassemia (5.9%), 20 with sickle
      cell disease (5.1%), and 13 with other hemoglobin abnormalities (3.3%), were
      studied. Complications were found to be as follows: cardiomyopathy in 45 of them
      (11.5%), diabetes mellitus in 10 (2.5%), hypothyroidism in 17 (4.3%),
      hypoparathyroidism in 2 (0.5%), osteoporosis in 53 (13.6%), growth retardation in
      110 (28.3%), and hypogonadism in 75 patients (19.3%). The incidence of
      autoantibody and alloantibody in patients with thalassemia major was 5.6% and
      10.5%, respectively. Transfusion-transmission diseases evaluated in patients
      found the incidence of hepatit A virus IgG to be 97.5%, that of HBs Ab to be
      99.5%, HBs Ag to be 0.5%, HCV Ab to be 18%, CMV IgG to be 72.3%, CMV IgM to be
      2%, and HIV-Ab to be 0%. Therefore, for the first time in our country the
      thalassemia center was established as a model and included subunits and a team.
      It served all patients for 15 years until the team was dispersed; thereafter,
      most of the patients were not followed up on a regular basis.

PMID- 23128338
TI  - Moderate aplastic anemia in children:  preliminary outcomes for treatment versus
      observation from a single-institutional experience.
AB  - INTRODUCTION: Because of the variety of definitions used to describe moderate
      aplastic anemia (MAA), we review our institutional experience period with
      patients who met a proposed set of criteria for this disorder. On an exploratory
      basis, we sought to evaluate the influence of treatment with immunosuppressive
      therapy (IST) versus observation on long-term outcomes. MATERIALS AND METHODS:
      Records from 1999 to 2010 were screened for patients who met the criteria for
      MAA: (1) bone marrow cellularity of 20% to 50%; (2) cytopenias in at least 1 cell
      line (absolute neutrophil count<1000/uL, hemoglobin<9 g/dL, platelet
      count<100,000/uL); (3) mean corpuscular volume >=90; (4) persistence >6 months;
      and (5) negative Fanconi studies. Data were collected for patient/disease
      characteristics, treatments, and outcomes. RESULTS: Eight patients met the
      criteria for MAA. Three of 8 patients received IST. Of 3 patients who received
      IST, complete response was observed in 2 and transfusion independence in 1, as
      compared with 2 of 5 and 3 of 5 in the group who were observed without IST.
      Median duration of follow-up was 48 months. DISCUSSION: As several patients
      spontaneously resolved, and none developed severe aplastic anemia, acute
      myelogenous leukemia, or myelodysplastic syndrome, the criteria used here may
      identify a group of children with favorable prognosis who can be managed
      supportively.

PMID- 23128339
TI  - Low serum lipocalin levels in patients with iron deficiency anemia.
AB  - In the recent literature, there are studies on the relationship between anemia
      and lipocalin, but there is no study regarding the relationship between lipocalin
      and iron deficiency anemia (IDA) up to date. In this study, we aimed to observe
      lipocalin levels at admission, and after iron therapy in children with IDA. We
      also compared our findings to those in healthy children. Sixty-one children
      admitted in our outpatient clinic were included in the study. Thirty of these
      children had IDA (study group) and the rest were healthy (control group). Thirty
      patients, meeting the IDA criteria, received oral ferrous sulfate of 4 mg/kg/d.
      As soon as the hemoglobin value reached >11 g/dL, half dose of oral ferrous
      sulfate therapy was continued for another month. Serum lipocalin levels before
      and after iron therapies were compared. Hematologic parameters and serum
      lipocalin levels were also compared between the 2 groups. Mean values of serum
      lipocalin were 31.01+/-14.46 and 74.77 ng/dL in patients with IDA at admission
      and at third month of therapy, respectively (P<0.0001). The same figure was
      57.35+/-39.51 ng/dL in the control group. Before treatment, mean values of
      lipocalin levels in patients with IDA was significantly lower than the control
      group (P=0.001); however, such a difference was not detected after 3 months of
      therapy (P=0.102). We suggest that decreased serum lipocalin levels in our
      patients during iron insufficiency were caused by iron deficiency rather than
      anemia.

PMID- 23128340
TI  - Detection, control, and management of a respiratory syncytial virus outbreak in a
      pediatric hematology-oncology department.
AB  - BACKGROUND: Immunocompromised patients are at increased risk for severe
      respiratory syncytial virus (RSV) infection. Palivizumab is approved for
      prevention of RSV in specific populations but not for treatment. Few studies
      demonstrated the safety and successful treatment with intravenous (IV)
      palivizumab. We describe our experience with IV palivizumab treatment for RSV in
      a pediatric hematology-oncology department during an outbreak. METHODS: During a
      short period of renovations, oncology patients were placed in a general pediatric
      ward. After a case of severe fatal RSV pneumonia in a 2-year-old male patient
      with acute myeloid leukemia, all patients were actively screened twice weekly
      regardless of symptoms. Respiratory samples were tested for RSV using rapid
      immunochromatography detection, immunofluorescence, or reverse transcriptase
      polymerase chain reaction. A single dose of palivizumab (15 mg/kg) was given to
      children below 3 years of age who tested positive for RSV. RESULTS: Over a 6-week
      period, 12 patients tested positive for RSV. Seven patients were treated with
      palivizumab. Five patients had respiratory symptoms, and 2 were asymptomatic. No
      adverse events were attributed to IV palivizumab treatment. Early-treated
      patients had no complications attributed to RSV. CONCLUSIONS: Containment of RSV
      outbreak in high-risk children is difficult. Screening with reverse transcriptase
      polymerase chain reaction and the early use of IV palivizumab is safe and may
      prevent complications of RSV infection among these patients.

PMID- 23128341
TI  - An assay for permeability of the zebrafish embryonic neuroepithelium.
AB  - The brain ventricular system is conserved among vertebrates and is composed of a
      series of interconnected cavities called brain ventricles, which form during the
      earliest stages of brain development and are maintained throughout the animal's
      life. The brain ventricular system is found in vertebrates, and the ventricles
      develop after neural tube formation, when the central lumen fills with
      cerebrospinal fluid (CSF) (1,2). CSF is a protein rich fluid that is essential
      for normal brain development and function(3-6). In zebrafish, brain ventricle
      inflation begins at approximately 18 hr post fertilization (hpf), after the
      neural tube is closed. Multiple processes are associated with brain ventricle
      formation, including formation of a neuroepithelium, tight junction formation
      that regulates permeability and CSF production. We showed that the Na,K-ATPase is
      required for brain ventricle inflation, impacting all these processes (7,8),
      while claudin 5a is necessary for tight junction formation (9). Additionally, we
      showed that "relaxation" of the embryonic neuroepithelium, via inhibition of
      myosin, is associated with brain ventricle inflation. To investigate the
      regulation of permeability during zebrafish brain ventricle inflation, we
      developed a ventricular dye retention assay. This method uses brain ventricle
      injection in a living zebrafish embryo, a technique previously developed in our
      lab(10), to fluorescently label the cerebrospinal fluid. Embryos are then imaged
      over time as the fluorescent dye moves through the brain ventricles and
      neuroepithelium. The distance the dye front moves away from the basal (non
      luminal) side of the neuroepithelium over time is quantified and is a measure of
      neuroepithelial permeability (Figure 1). We observe that dyes 70 kDa and smaller
      will move through the neuroepithelium and can be detected outside the embryonic
      zebrafish brain at 24 hpf (Figure 2). This dye retention assay can be used to
      analyze neuroepithelial permeability in a variety of different genetic
      backgrounds, at different times during development, and after environmental
      perturbations. It may also be useful in examining pathological accumulation of
      CSF. Overall, this technique allows investigators to analyze the role and
      regulation of permeability during development and disease.

PMID- 23128343
TI  - Self-rated health predicts mortality and graft loss after kidney transplantation:
      a 10-year follow-up study.
AB  - BACKGROUND: This study explored whether self-rated health (SRH) shortly after
      kidney transplantation (KT) predicts mortality and graft loss at up to 10 years'
      follow-up. METHODS: A total of 276 patients shortly after successful KT were
      interviewed. SRH was measured using the first item of the SF-36 questionnaire and
      divided into three tertiles: poor, average and excellent health. Clinical data
      were retrieved from medical records. Cox regression was used to identify whether
      different levels of SRH predicted mortality and graft loss in transplant
      recipients. The observation period was up to 10 years. RESULTS: Poor SRH (HR
      11.1, p < 0.001), average SRH (HR 4.21, p < 0.05), estimated glomerular
      filtration rate (HR 0.26, p < 0.05) and age (HR 1.04, p < 0.05) were
      significantly associated with mortality. Similarly, poor SRH (HR 6.4, p < 0.001),
      average SRH (HR 3.6, p < 0.05), new-onset diabetes mellitus after KT (HR 3.3, p <
      0.05) and chronic renal allograft dysfunction (HR 3.7, p < 0.00) were
      significantly associated with graft loss. CONCLUSION: Poor SRH shortly after
      transplantation indicates an increased risk of mortality and graft loss at up to
      10 years' follow-up. SRH could be an inexpensive and reliable indicator for
      starting diagnostic and/or treatment strategies. The usefulness of SRH compared
      to other global clinical measures predicting mortality and graft loss should also
      be studied.

PMID- 23128344
TI  - Risk factors for resistance to proton pump inhibitor maintenance therapy for
      reflux esophagitis in Japanese women over 60 years.
AB  - AIM: The aim of this study was to evaluate risk factors for proton pump inhibitor
      (PPI) resistance in older Japanese female patients with reflux esophagitis
      evaluated by physicians. METHODS: The study included 462 Japanese female patients
      aged over 60 years with reflux esophagitis who received PPI maintenance therapy
      for more than 6 months. RESULTS: The characteristics of all 462 patients were:
      age: 76.4 +/- 7.6 years, height: 147.2 +/- 6.1 cm, weight: 49.9 +/- 8.4 kg and
      body mass index: 24.0 +/- 3.5. The reflux esophagitis grades were A in 69.5%, B
      in 15.8%, C in 9.1% and D in 5.6%. Helicobacter pylori was positive in 60.6%.
      Regarding PPI maintenance therapy for clinical symptoms evaluated by the
      attending physicians, 66.7% were 'good control', 26.8% were 'reasonable control'
      and 6.5% were 'bad control: resistant'. PPI maintenance therapy was less
      effective in patients with more severe reflux esophagitis of grades C and D (OR:
      0.027; 95% CI: 0.010-0.077) and negative H. pylori infection status (OR: 4.470;
      95% CI: 1.631-12.247). Lumbar kyphosis and hiatus hernia were risk factors for
      severity grading of reflux esophagitis. CONCLUSIONS: PPI maintenance therapy
      evaluated by attending physicians indicated that reflux esophagitis severity and
      negative H. pylori status were risk factors for treatment resistance.

PMID- 23128346
TI  - [Prison health care, a borderline medicine].

PMID- 23128345
TI  - Multiplexed tracking of protease activity using a single color of quantum dot
      vector and a time-gated Forster resonance energy transfer relay.
AB  - Semiconductor quantum dots (QDs) are attractive probes for optical sensing and
      imaging due to their unique photophysical attributes and nanoscale size. In
      particular, the development of assays and biosensors based on QDs and Forster
      resonance energy transfer (FRET) continues to be a prominent focus of research.
      Here, we demonstrate the application of QDs as simultaneous donors and acceptors
      in a time-gated FRET relay for the multiplexed detection of protease activity. In
      contrast to the current state-of-the-art, which uses multiple colors of QDs,
      multiplexing was achieved using only a single color of QD. The other constituents
      of the FRET relay, a luminescent terbium complex and fluorescent dye, were
      assembled to QDs via peptides that were selected as substrates for the model
      proteases trypsin and chymotrypsin. Loss of prompt FRET between the QD and dye
      signaled the activity of chymotrypsin; loss of time-gated FRET between the
      terbium and QD signaled the activity of trypsin. We applied the FRET relay in a
      series of quantitative, real-time kinetic assays of increasing biochemical
      complexity, including multiplexed sensing, measuring inhibition in a multiplexed
      format, and tracking the proteolytic activation of an inactive pro-protease to
      its active form in a coupled, multienzyme system. These capabilities were derived
      from a ratiometric analysis of the two FRET pathways in the relay and permitted
      extraction of initial reaction rates, enzyme specificity constants, and apparent
      inhibition constants. This work adds to the growing body of research on
      multifunctional nanoparticles and introduces multiplexed sensing as a novel
      capability for a single nanoparticle vector. Furthermore, the ability to track
      both enzymes within a coupled biological system using one vector represents a
      significant advancement for nanoparticle-based biosensing. Prospective
      applications in biochemical research, applied diagnostics, and drug discovery are
      discussed.

PMID- 23128347
TI  - [Validity of the International Personality Disorder Examination (IPDE)
      questionnaire in a sample of prison inmates].
AB  - OBJECTIVE: To discover the validity indices and establish the most adequate cut
      off point when using the IPDE questionnaire on a sample of prison inmates.
      MATERIALS AND METHODS: A transversal study was carried out on a correlatively
      selected sample of 100 inmates at two prisons in Madrid. Evaluation instruments,
      a questionnaire for demographic, prison and toxicological data and a complete
      interview and IPDE assessment questionnaire (version DSM-IV) were utilised as
      well as a conditional probability study of the IPDE questionnaire with different
      cut off points based on the use of the IPDE interview as the "gold standard".
      RESULTS: The cut off point of 3 or more non-coincident answers showed low
      specificity (2.5%) for the presence of one or more personality disorders, and low
      sensitivity to antisocial (56.7%) and borderline (58.8%) personality disorders.
      Discusion: The IPDE questionnaire of little use amongst the studied prison
      population when the habitual reference standards were applied due to the very
      high number of false positives that were produced. The best validity indices for
      identifying one or more personality disorders are obtained with a probable cut
      off point being equal to 4 or more answers that do not coincide with those
      expected. The IPDE questionnaire was of no great benefit for the inmates in this
      study because, even when using the habitual cut off point of 3 or more non
      coincident questions, sensibility to antisocial and borderline personality
      disorders, which are the most common PDs amongst the sample group, was found to
      be low.

PMID- 23128348
TI  - [Drug use when entering prison: comparison between the spanish and foreign prison
      inmate population].
AB  - INTRODUCTION: There are few studies comparing drug use behaviours between the
      local and immigrant prison populations. METHOD: Descriptive and prospective
      study. Comparisons were made between the Spanish and foreign population of
      prisoners who entered prison for the first time between 01/01/2005 and
      31/12/2005. Socio-demographic descriptive variables were attained along with data
      about drug use in the month prior to entry into prison. X2 was used to compare
      qualitative variables and Student's t distribution for quantitative ones.
      Posterior binary logistic regression was used for calculating the Odds Ration for
      statistically significant variables. RESULTS: 246 individuals were included, 230
      (93.5%) were men. 89 (36%) were Spanish and 157 (64%) foreigners. The average age
      was 31.9 (IC95%: 30.6-33.1). The average age was higher amongst Spanish inmates
      (33.9 vs. 30.7; p=0.023). Spanish inmates smoked less (79, 40.9%) than foreigners
      (114, 59.1%) p=0.003 and consumed less alcohol (51, 42.5% vs. 69, 57.5%),
      p=0.044. The use of heroin, cocaine, designer drugs and non-prescribed
      benzodiazepines, individually or in combinations, was admitted to by 68
      individuals, 44 (64.7%) of whom were Spanish, and 24 (35.3%) were foreigners (OR:
      5.4, IC95%: 2.9-9.9, p>0.0001). The only consumption type where no significant
      difference between the two groups could be seen was in "designer drug" use: 5
      (5.6%) vs. 2 (1.3%). (OR: 4.6, IC95%: 0.8-24.3, p=0.07). IVD use was rare and
      more common amongst Spanish inmates: 3 (3.4%) vs. 0 (0%) (p=0.02). CONCLUSIONS:
      Foreigners make up the majority of the recent intake into prison. Spanish
      prisoners are older. Spanish inmates consume more illegal drugs, while foreign
      prisoners consume more socially accepted drugs.

PMID- 23128349
TI  - [Mental health characteristics of men who abuse their intimate partners].
AB  - The prevalence of psychopathological disorders amongst men who abuse their
      intimate partners has yet to be established. This article reviews studies carried
      out to ascertain the mental health characteristics of male domestic abusers. Most
      of these studies are based on samples of abusers under treatment or in prison.
      They generally assess the presence of psychopathological disorders through self
      reports and diagnostic interviews are infrequently used. The results of this
      research show that domestic abusers tend to obtain high points for some types of
      personality disorders, especially narcissistic, antisocial and borderline
      disorders. They also present symptoms of depressive disorders and consumption of
      drugs and alcohol. Some studies also show that neurological problems are
      relatively frequent. Finally I discuss the limitations of current research and
      the implications for treatment of domestic abusers.

PMID- 23128350
TI  - [A smoking cessation program for prison inmates and personnel].
AB  - The main aim of this initiative is to promote a culture change in the
      prison/tobacco conjunction by means of an intervention program that leads to
      reduction in the high levels of smoking amongst the prison population (70-80%)
      and prison personnel. We hope to demonstrate that it is possible in practice to
      successfully implant and extend tobacco cessations programs in prisons. This
      would mean an important step forward for the general health of prison inmates,
      who suffer from higher levels of tobacco addiction than the general population
      and prison staff, who for their part are forced to share a reduced and enclosed
      space with prisoners.

PMID- 23128351
TI  - The basic needs of prisoners in Eastern Europe correctional institutions and its
      implications for mental health: The Lithuanian case.

PMID- 23128352
TI  - Prevalence, treatment and control of hypertension in a Croatian endemic
      nephropathy area.
AB  - BACKGROUND: Hypertension is not considered to be a characteristic of endemic
      nephropathy (EN). Recent observations suggested that it might be more prevalent
      than it was reported before. AIM: The aim of our study was to analyze prevalence,
      treatment and control of hypertension in a Croatian endemic area. METHODS: In the
      present cross-sectional study, 1,602 farmers were enrolled, 1,246 from EN and 356
      from control villages. Epidemiological and medical histories were taken and
      clinical and laboratory examinations performed for kidney function. Blood
      pressure was measured following the ESH/ESC guidelines. RESULTS: The prevalence
      of hypertension in EN villages was higher than in control (50.8 vs. 46.5%, p =
      0.005). There was no difference in overall treatment, control of all and treated
      hypertensives between the villages. In all villages, women were treated more than
      men (EN 41.6 vs. 28.4%, p < 0.001; control 46.4 vs. 27.3%, p < 0.001), but better
      control of treated was achieved in men (EN 24.7 vs. 17.4%, p = 0.002; control
      29.6 vs. 15.5%, p = 0.002). Women had lower income and level of education than
      men (p < 0.01). CONCLUSION: Hypertension is highly prevalent in endemic villages.
      In all villages, men had better blood pressure control despite being treated
      less. This finding could be explained by poorer education and income in women.

PMID- 23128353
TI  - Cell cycle regulation by glucosamine in human pulmonary epithelial cells.
AB  - Airway epithelial cells play an important role against intruding pathogens.
      Glucosamine, a commonly used supplemental compound, has recently begun to be
      regarded as a potential anti-inflammatory molecule. This study aimed to uncover
      how glucosamine impacts on cellular proliferation in human alveolar epithelial
      cells (A549) and bronchial epithelial cells (HBECs). With trypan blue-exclusion
      assay, we observed that glucosamine (10, 20, 50 mM) caused a decrease in cell
      number at 24 and 48 h; with a flow cytometric analysis, we also noted an enhanced
      cell accumulation within the G(0)/G(1) phase at 24 h and induction of late
      apoptosis at 24 and 48 h by glucosamine (10, 20, 50 mM) in A549 cells and HBECs.
      Examination of phosphorylation in retinoblastoma (Rb) protein, we found an
      inhibitory effect by glucosamine at 20 and 50 mM. Glucosamine at 50 mM was
      demonstrated to elevate both the mRNA and protein expression of p53 and heme
      oxygenase-1 (HO-1), but also caused a reduction in p21 protein expression. In
      addition, glucosamine attenuated p21 protein stability via the proteasomal
      proteolytic pathway, as well as inducing p21 nuclear accumulation. Altogether,
      our results suggest that a high dose of glucosamine may inhibit cell
      proliferation through apoptosis and disturb cell cycle progression with a halt at
      G(0)/G(1) phase, and that this occurs, at least in part, by a reduction in Rb
      phosphorylation together with modulation of p21, p53 and HO-1 expression, and
      nuclear p21 accumulation.

PMID- 23128354
TI  - Inhibition of HIV-1 replication by RNA with a microRNA-like function.
AB  - Human immunodeficiency virus type 1 (HIV-1) replication is suppressed by a small
      guide RNA (sgRNA) that targets the packaging signal of HIV-1 RNA. We
      unintentionally produced a plasmid with the reverse sequence of the sgRNA and its
      terminator (pR-Psi-sgRNA-ter). Both sgRNA and R-Psi-sgRNA suppress HIV-1, but the
      mechanism by which R-Psi-sgRNA suppresses HIV is not clear. To evaluate whether
      the suppressive effect is caused by an RNA interference or microRNA (miRNA)-like
      mechanism, R-Psi-sgRNA was synthesized in vitro and treated with the Dicer
      enzyme, an important enzyme for RNA interference and miRNA. The RNA was cleaved
      into fragments of approximately 24 nucleotides (nt). We analyzed the sequence of
      the RNA fragments and predicted the RNA secondary structure of R-Psi-sgRNA to
      determine the region recognized by the Dicer enzyme. The lengths of the R-Psi
      sgRNA fragments ranged from 48 to 140 nt, and were predicted to form double
      strands, including mismatches, in this region. An HIV-1 p24 assay indicated that
      the R-Psi-sgRNA fragments suppressed HIV-1 replication. These findings suggest
      that R-Psi-sgRNA acts as a miRNA to inhibit HIV-1.

PMID- 23128356
TI  - Palladium-catalyzed formation of phenolic compounds by reaction of carbonyl
      compounds with carbon dioxide.
AB  - The use of carbon dioxide as a renewable and environmentally friendly source of
      carbon is highly attractive. A novel and efficient protocol for the synthesis of
      phenolic compounds from carbonyl compounds and carbon dioxide in the presence of
      a catalytic amount of Pd(OAc)(2) has been developed. This reaction is appealing
      for industries and is a tool for the sequestration of carbon dioxide.

PMID- 23128355
TI  - Symmetrically reduced stiffness and increased extensibility in compression and
      tension at the mineralized fibrillar level in rachitic bone.
AB  - In metabolic bone diseases, the alterations in fibrillar level bone-material
      quality affecting macroscopic mechanical competence are not well-understood
      quantitatively. Here, we quantify the fibrillar level deformation in cantilever
      bending in a mouse model for hereditary rickets (Hpr). Microfocus in-situ
      synchrotron small-angle X-ray scattering (SAXS) combined with cantilever bending
      was used to resolve nanoscale fibril strain in tensile- and compressive tissue
      regions separately, with quantitative backscattered scanning electron microscopy
      used to measure microscale mineralization. Tissue-level flexural moduli for Hpr
      mice were significantly (p<0.01) smaller compared to wild-type (~5 to 10-fold
      reduction). At the fibrillar level, the fibril moduli within the tensile and
      compressive zones were significantly (p<0.05) lower by ~3- to 5-fold in Hpr mice
      compared to wild-type mice. Hpr mice have a lower mineral content (24.2+/
      2.1Cawt.% versus 27.4+/-3.3Ca wt.%) and its distribution was more heterogeneous
      compared to wild-type animals. However, the average effective fibril modulus did
      not differ significantly (p>0.05) over ages (4, 7 and 10weeks) between tensile
      and compressive zones. Our results indicate that incompletely mineralized fibrils
      in Hpr mice have greater deformability and lower moduli in both compression and
      tension, and those compressive and tensile zones have similar moduli at the
      fibrillar level.

PMID- 23128357
TI  - Au25 nanocluster-catalyzed Ullmann-type homocoupling reaction of aryl iodides.
AB  - The Au(25)(SR)(18)/CeO(2) nanocluster catalyst showed high activity in the
      homocoupling of aryl iodides (e.g. up to 99.8% yield with iodobenzene) and
      excellent recyclability.

PMID- 23128358
TI  - In-vitro comparison of free oscillation rheometry (ReoRox) and rotational
      thromboelastometry (ROTEM) in trauma patients upon hospital admission.
AB  - Plasma-based assays do not provide accurate information on haemostatic
      resuscitation hence viscoelastic point-of-care haemostatic assays such as
      rotational thromboelastometry (ROTEM Delta, Pentapharm) are used to monitor
      coagulopathy in trauma patients. Free oscillation rheometry (FOR) is a new whole
      blood haemostatic assay that measures not only the clot-forming process but also
      the initial viscous phase; this could potentially be of value when assessing
      traumatic coagulopathy. A comparative analysis between FOR and ROTEM was
      therefore performed. This is a prospective observational study of 40 adult trauma
      patients admitted to a level 1 trauma centre. Citrated whole blood was analysed
      with ROTEM EXTEM and FIBTEM assays and FOR Fibscreen1 and Fibscreen2 assays.
      Predefined variables of ROTEM and FOR were compared using Spearman's rho. ROTEM
      maximum clot function (MCF) in both EXTEM and FIBTEM correlated (P < 0.0001 for
      both) with FOR maximum elasticity Fibscreen1 and Fibscreen2, respectively.
      Interestingly, ROTEM EXTEM clotting time did not correlate with any of the FOR
      clot initiation parameters COT1, COT2 or COT2-1 of Fibscreen1. A correlation
      between ROTEM EXTEM and FIBTEM and FOR Fibscreen1 and Fibscreen2 clot formation
      and clot strength was found as was a significant correlation between lysis index
      after 60 min and ClotSR30. ROTEM EXTEM did not correlate with COT1, COT2 or COT2
      1 of Fibscreen1 and this warrants further investigation.

PMID- 23128359
TI  - Rapamycin as longevity enhancer and cancer preventative agent in the context of
      p53 deficiency.
AB  - Comment on: 1. Komarova et al. Rapamycin extends lifespan and delays
      tumorigenesis in heterozygous p53+/- mice. Aging. 2012; 4:10 2. Comas et al. New
      nanoformulation of rapamycin Rapatar extends lifespan in homozygous p53-/- mice
      by delaying carcinogenesis. Aging.2012; 4;10.

PMID- 23128360
TI  - Design and synthesis of regioisomeric triazole based peptidomimetic macrocycles
      and their dipole moment controlled self-assembly.
AB  - Two peptidomimetic macrocycles, regioisomeric in terms of the position of
      triazole/amide, have been synthesized. Both undergo self-assembly in a parallel
      manner but in solvents of opposite polarity, ascribed to (beta, beta) and (beta
      D, beta-L) hydrogen bonding leading to formation of two different unique classes
      of organic nanostructures.

PMID- 23128361
TI  - Disease mechanisms in MS: informing tactics to combat MS.

PMID- 23128362
TI  - Bias in pertussis incidence data and its implications for public health
      epidemiology.

PMID- 23128363
TI  - Mapping cortical dynamics using simultaneous MEG/EEG and anatomically-constrained
      minimum-norm estimates: an auditory attention example.
AB  - Magneto- and electroencephalography (MEG/EEG) are neuroimaging techniques that
      provide a high temporal resolution particularly suitable to investigate the
      cortical networks involved in dynamical perceptual and cognitive tasks, such as
      attending to different sounds in a cocktail party. Many past studies have
      employed data recorded at the sensor level only, i.e., the magnetic fields or the
      electric potentials recorded outside and on the scalp, and have usually focused
      on activity that is time-locked to the stimulus presentation. This type of event
      related field / potential analysis is particularly useful when there are only a
      small number of distinct dipolar patterns that can be isolated and identified in
      space and time. Alternatively, by utilizing anatomical information, these
      distinct field patterns can be localized as current sources on the cortex.
      However, for a more sustained response that may not be time-locked to a specific
      stimulus (e.g., in preparation for listening to one of the two simultaneously
      presented spoken digits based on the cued auditory feature) or may be distributed
      across multiple spatial locations unknown a priori, the recruitment of a
      distributed cortical network may not be adequately captured by using a limited
      number of focal sources. Here, we describe a procedure that employs individual
      anatomical MRI data to establish a relationship between the sensor information
      and the dipole activation on the cortex through the use of minimum-norm estimates
      (MNE). This inverse imaging approach provides us a tool for distributed source
      analysis. For illustrative purposes, we will describe all procedures using
      FreeSurfer and MNE software, both freely available. We will summarize the MRI
      sequences and analysis steps required to produce a forward model that enables us
      to relate the expected field pattern caused by the dipoles distributed on the
      cortex onto the M/EEG sensors. Next, we will step through the necessary processes
      that facilitate us in denoising the sensor data from environmental and
      physiological contaminants. We will then outline the procedure for combining and
      mapping MEG/EEG sensor data onto the cortical space, thereby producing a family
      of time-series of cortical dipole activation on the brain surface (or "brain
      movies") related to each experimental condition. Finally, we will highlight a few
      statistical techniques that enable us to make scientific inference across a
      subject population (i.e., perform group-level analysis) based on a common
      cortical coordinate space.

PMID- 23128365
TI  - Prognostic significance of invasion depth in oral tongue squamous cell carcinoma.
AB  - PURPOSE: Staging for tongue carcinoma does not consider its depth of invasion. We
      aim to determine the prognostic significance of invasion depth in tongue cancer.
      MATERIALS AND METHODS: Retrospective review of patients with tongue carcinoma who
      underwent curative surgery between 2002 and 2005; 67 patients were analyzed.
      Tumors were divided into 2 groups: group A = invasion depth <4 mm; group B =
      invasion depth >=4 mm. Recurrence and survival rates were calculated for each
      group and compared. RESULTS: The local recurrence rate in group B was
      significantly higher (10 vs. 29.7%, p = 0.048). Group A patients had a superior 5
      year overall survival (68.8 vs. 41.6%, p = 0.012), disease-specific survival
      (67.1 vs. 41.1%, p = 0.026) and local recurrence-free survival (89.5 vs. 65.4%, p
      = 0.035). Five-year regional recurrence, locoregional recurrence and distant
      recurrence-free survival rates were not significantly different between the 2
      groups (p = 0.390, p = 0.173 and p = 0.207). The impact of invasion depth on
      survival was maintained on multivariate analysis (p = 0.031). CONCLUSION:
      Invasion depth is an important prognostic indicator in tongue cancer.

PMID- 23128366
TI  - A randomized comparison of print and web communication on colorectal cancer
      screening.
AB  - BACKGROUND: New methods to enhance colorectal cancer (CRC) screening rates are
      needed. The web offers novel possibilities to educate patients and to improve
      health behaviors, such as cancer screening. Evidence supports the efficacy of
      health communications that are targeted and tailored to improve the uptake of
      recommendations. METHODS: We identified unscreened women at average risk for CRC
      from the scheduling databases of obstetrics and gynecology practices in 2 large
      health care systems. Participants consented to a randomized controlled trial that
      compared CRC screening uptake after receipt of CRC screening information
      delivered via the web or in print form. Participants could also be assigned to a
      control (usual care) group. Women in the interventional arms received tailored
      information in a high- or low-monitoring Cognitive Social Information Processing
      model-defined attentional style. The primary outcome was CRC screening
      participation at 4 months. RESULTS: A total of 904 women were randomized to the
      interventional or control group. At 4 months, CRC screening uptake was not
      significantly different in the web (12.2%), print (12.0%), or control (12.9%)
      group. Attentional style had no effect on screening uptake for any group. Some
      baseline participant factors were associated with greater screening, including
      higher income (P = .03), stage of change (P < .001), and physician recommendation
      to screen (P < .001). CONCLUSIONS: A web-based educational intervention was no
      more effective than a print-based one or control (no educational intervention) in
      increasing CRC screening rates in women at average risk of CRC. Risk messages
      tailored to attentional style had no effect on screening uptake. In average-risk
      populations, use of the Internet for health communication without additional
      enhancement is unlikely to improve screening participation. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00459030.

PMID- 23128367
TI  - Pretreatment parameters obtained from peripheral blood sample predicts
      invasiveness of bladder carcinoma.
AB  - PURPOSE: To predict the invasiveness of urothelial bladder carcinoma using a
      logistic regression model on preoperative peripheral blood samples. PATIENTS AND
      METHODS: Hospital data of patients operated for urothelial carcinoma were
      reviewed retrospectively. Preoperative blood samples were collected before the
      first cystoscopic examination. Any kind of infection or inflammation was an
      exclusion criterion. Patients were grouped as having a non-muscle-invasive or
      muscle-invasive urothelial carcinoma. The mean age was 69 years and was
      determined as the cut-off value. According to receiver operating characteristic
      curves, threshold points were determined for lymphocytes, neutrophil count,
      neutrophil-to-lymphocyte ratio (NLR), thrombocytes and mean platelet volume.
      Demographic specialties, parameters obtained from blood samples, tumor size and
      multiplicity were evaluated and significant parameters were put into a logistic
      regression model. RESULTS: The study group consisted of 80 non-muscle-invasive
      and 102 muscle-invasive patients. Age (<=69 vs. >69), female gender, NLR (2.57),
      mean platelet volume (7.9/fl) and platelet count (400,000/ul) were significant
      parameters and put in a model. Using odds ratios, the probability of tumor
      invasiveness was calculated by a formula. CONCLUSION: Age, female gender, NLR and
      platelet count were found to be the predictors of invasiveness of urothelial
      carcinoma.

PMID- 23128368
TI  - Association between nonalcoholic liver disease and chronic kidney disease: an
      ultrasound analysis from NHANES 1988-1994.
AB  - BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) has been proposed to
      contribute to chronic kidney disease (CKD) independently of traditional
      cardiometabolic risk factors. We hypothesized that NAFLD is associated with CKD
      and that greater severity of NAFLD is associated with higher odds of CKD.
      METHODS: A cross-sectional analysis of 11,469 adults who participated in the
      National Health and Nutrition Examination Survey (NHANES) 1988-1994. NAFLD was
      defined by ultrasonographic detection of steatosis in the absence of other liver
      diseases. CKD was defined as an estimated glomerular filtration rate of <=60
      ml/min/1.73 m(2) or the presence of albuminuria in subjects with an estimated
      glomerular filtration rate of >60 ml/min/1.73 m(2). RESULTS: 2,891 (25.4%)
      patients in the cohort had CKD. The prevalence of NAFLD was higher in individuals
      with CKD compared to those without CKD (42.2 vs. 34.5%, p < 0.0001). NAFLD was
      associated with CKD in unadjusted logistic regression analysis (OR = 1.47, 95%
      CI: 1.29-1.67, p < 0.0001). Adjustment for demographics and components of
      metabolic syndrome attenuated this relationship (OR = 1.04, 95% CI: 0.88-1.23, p
      = 0.64). Moderate and severe NAFLD on ultrasound were increasingly associated
      with prevalent CKD in unadjusted analysis, but not after adjustment for metabolic
      syndrome components. CONCLUSION: After adjusting for features of metabolic
      syndrome, ultrasound-diagnosed NAFLD is not associated with prevalent CKD among
      US adults. Aggressive public health efforts are needed to prevent and treat
      metabolic syndrome.

PMID- 23128369
TI  - Centralization of highly complex low-volume procedures in upper gastrointestinal
      surgery. A summary of systematic reviews and meta-analyses.
AB  - Centralization of complex upper gastrointestinal (GI) surgery and the effect on
      postoperative outcomes, especially mortality, has been reported extensively in
      the literature. In this review the highest level of evidence on the volume
      outcome relationship is discussed together with other important aspects that can
      influence postoperative outcomes. Do high-volume centers and surgeons result in
      better outcomes after surgery for the different upper GI surgical procedures such
      as esophageal, gastric, liver and pancreatic tumors? Twelve systematic reviews
      including four meta-analyses described the effect of hospital and/or surgeon
      volume on mortality. The majority of reviews (>90%) showed a lower mortality in
      high-volume hospitals. This correlation was also reported when analyzing the
      different GI procedures separately for esophageal, gastric, hepatic and
      pancreatic tumors. The volume discussion has limitations and therefore the
      relationship between hospital structure and process of care in hospitals and the
      outcome of surgery has also been acknowledged. Besides surgeon expertise and
      skills, high-intensity intensive care units, 24/7 availability of interventional
      radiology, effective prevention and managing of complications and adequate
      patient selection will influence postoperative outcomes. These forms of hospital
      structures and process of care might even play a more important role in surgical
      outcomes.

PMID- 23128370
TI  - Effects of UV radiation on the taxonomic composition of natural bacterioplankton
      communities from Bahia Engano (Patagonia, Argentina).
AB  - In order to gain insights into the effects of solar ultraviolet radiation (UVR,
      280-400 nm) on the composition of marine bacterioplankton communities from South
      Atlantic waters - Bahia Engano (Patagonia, Argentina), we performed microcosms
      experiments during the Austral summer of 2010. Water samples were exposed to
      three solar radiation treatments in 25 L microcosms during 8 days: PAR+UV-A+UV-B
      (280-700 nm; PAB treatment), PAR+UV-A (320-700 nm; PA treatment), and PAR only
      (400-700 nm; P treatment). The taxonomic composition of the bacterial
      communities, at the beginning and at the end of the experiment, were studied by
      the analyses of 16S rDNA gene libraries. Multivariate and phylogenetic analyses
      demonstrated substantial differences in the community composition so that the
      samples exposed to PAR and PAR+UV-A presented more similar taxa assemblages among
      them than compared to the PAR+UV-A+UV-B exposed one. Our results indicate that
      overall, exposure to different radiation treatments can shape the taxonomic
      composition of marine bacterial populations, grown in microcosms, from this
      Patagonian area.

PMID- 23128371
TI  - [Concerning the congress].

PMID- 23128372
TI  - [Prevalence of psychiatric disorders on patients admissed by the Psychiatric
      Service in the Security Area of H.U.M.S. (University Hospital "Miguel Servet")].
AB  - INTRODUCTION: recent epidemiological studies highlight an increase in the
      prevalence of psychiatric disorders amongst prison inmates. The objective of this
      study to determine the most prevalent primary and secondary psychiatric
      disorders, socio-demographic data and average stay period amongst patients
      admitted to the Prison Unit of a general hospital as charges of the Psychiatric
      Service. MATERIALS AND METHODS: retrospective cross-sectional descriptive study.
      The sample group consisted of a number of patients admitted into the Prison Unit
      as charges of the Psychiatric Service during a five year period (n=136). RESULTS:
      90,4% were men and 9,6% were women. The average age was 34,18 years. The most
      prevalent primary psychiatric diagnoses were: Personality Disorder 22%, and
      Schizophrenic Disorder 16,3%. The most prevalent secondary psychiatric diagnoses
      were: Personality Disorder 11,9%, Substance Abuse 10,7%. CONCLUSIONS: the most
      prevalent primary and secondary psychiatric diagnosis was personality disorder.
      The existence of a high level of comorbidity of substance abuse-dependence was
      recorded. Prisons currently lack Mental Health multidisciplinary teams. This
      often means that the inmate must be transferred to a hospital with the increased
      work load and financial cost that this implies.

PMID- 23128373
TI  - [HIV, hepatitis B and syphilis infection in inmates of Venezuela's prisons, 1998
      2001].
AB  - OBJECTIVE: To determine the prevalence of HIV, Hepatitis B and syphilis amongst
      inmates during the time period 1998-2001. MATERIALS AND METHODS: Descriptive,
      cross-sectional study carried out at 6 prisons using a volunteer sample of 1773
      inmates. Blood samples were gathered and analysed using enzyme linked
      immunoassays (ELISA) and RPR screening tests to identify the presence of HIV
      antibodies, Hepatitis B anti-core antibodies and treponema pallidum. RESULTS: 456
      cases gave a positive response to tests, 70 (4,0%) of which gave positive results
      for HIV, 280 (16,2%) for Hepatitis B and 106 (6,1%) for syphilis. The greatest
      percentage of HIV cases were found amongst the youngest inmates (18 to 37 years).
      The number of Hepatitis B cases increased progressively in line with age until
      reaching a maximum percentage in the 48-57 age group. No significant statistical
      difference for age was observed in syphilis cases, but differences were found
      amongst HIV positive and Hepatitis B cases for age, length of sentence and number
      of prisons where inmate resided.

PMID- 23128374
TI  - [Psychosocial correlates of the adherence to antirretroviral treatment of men in
      Penitentiary Center of Barcelona].
AB  - OBJECTIVE: to assess therapeutic adherence to HAART amongst HIV positive inmates
      and its likely relationship with sets of different variables. MATERIALS AND
      METHODS: longitudinal study carried out at the Men's Prison of Barcelona (Centro
      Penitenciario de Hombres de Barcelona). The prison data base, a semi-structured
      interview assessing socio-penal, demographic and clinical variables as well as
      treatment characteristics, and questionnaires on beliefs and emotional states
      were used. Adherence at the beginning of the study, and then after three and six
      months was also assessed. RESULTS: inmates presented with low levels of social
      support, and showed moderate agreement regarding care received from medical and
      health personnel. They considered the level of treatment complexity to be high
      and gave moderate relevance to treatment side effects. They presented high
      agreement with the potential benefits of continuing with the treatment and showed
      moderate perception of the severity of the illness. They also showed high levels
      of self efficacy where treatment monitoring was concerned. The emotional
      variables showed low blood pressure, depression, anger and fatigue. Adherence to
      antiretroviral treatment did not vary throughout the study period. Socio
      cognitive variables that correlated with adherence at different times of the
      study were self efficacy, perceived benefits, treatment complexity and side
      effects. Emotional states that correlated with adherence were depression and
      fatigue. DISCUSSION: the relationship between self efficacy and adherence is
      frequently mentioned in studies on the prediction of HAART adherence. The
      relationship between the two factors of fatigue and sadness/depression and
      adherence was expected.

PMID- 23128375
TI  - [Ethical and moral considerations of refusal of medical treatment by inmate
      patients].
AB  - A health care relationship is based on classic premises of autonomy, benefit to
      the patient, justice and non-maleficence (or the "do no harm" principle). Moral
      rules are principles that should guide professional conduct, they have no legal
      power but are self imposed by the group and oblige all professionals to act
      accordingly. Although the capacity of any imprisoned individual to make decisions
      about medical treatment is restricted, there are no ethical or moral arguments to
      justify limitations on the exercise of autonomy where decision making processes
      that might directly affect him/her are concerned.

PMID- 23128376
TI  - Magnetic properties and energy-mapping analysis.
AB  - The magnetic energy levels of a given magnetic solid are closely packed in energy
      because the interactions between magnetic ions are weak. Thus, in describing its
      magnetic properties, one needs to generate its magnetic energy spectrum by
      employing an appropriate spin Hamiltonian. In this review article we discuss how
      to determine and specify a necessary spin Hamiltonian in terms of first
      principles electronic structure calculations on the basis of energy-mapping
      analysis and briefly survey important concepts and phenomena that one encounters
      in reading the current literature on magnetic solids. Our discussion is given on
      a qualitative level from the perspective of magnetic energy levels and electronic
      structures. The spin Hamiltonian appropriate for a magnetic system should be
      based on its spin lattice, i.e., the repeat pattern of its strong magnetic bonds
      (strong spin exchange paths), which requires one to evaluate its Heisenberg spin
      exchanges on the basis of energy-mapping analysis. Other weaker energy terms such
      as Dzyaloshinskii-Moriya (DM) spin exchange and magnetocrystalline anisotropy
      energies, which a spin Hamiltonian must include in certain cases, can also be
      evaluated by performing energy-mapping analysis. We show that the spin
      orientation of a transition-metal magnetic ion can be easily explained by
      considering its split d-block levels as unperturbed states with the spin-orbit
      coupling (SOC) as perturbation, that the DM exchange between adjacent spin sites
      can become comparable in strength to the Heisenberg spin exchange when the two
      spin sites are not chemically equivalent, and that the DM interaction between
      rare-earth and transition-metal cations is governed largely by the magnetic
      orbitals of the rare-earth cation.

PMID- 23128377
TI  - Fast multigrid-based computation of the induced electric field for transcranial
      magnetic stimulation.
AB  - In transcranial magnetic stimulation (TMS), the distribution of the induced
      electric field, and the affected brain areas, depends on the position of the
      stimulation coil and the individual geometry of the head and brain. The
      distribution of the induced electric field in realistic anatomies can be modelled
      using computational methods. However, existing computational methods for
      accurately determining the induced electric field in realistic anatomical models
      have suffered from long computation times, typically in the range of tens of
      minutes or longer. This paper presents a matrix-free implementation of the finite
      element method with a geometric multigrid method that can potentially reduce the
      computation time to several seconds or less even when using an ordinary computer.
      The performance of the method is studied by computing the induced electric field
      in two anatomically realistic models. An idealized two-loop coil is used as the
      stimulating coil. Multiple computational grid resolutions ranging from 2 to 0.25
      mm are used. The results show that, for macroscopic modelling of the electric
      field in an anatomically realistic model, computational grid resolutions of 1 mm
      or 2 mm appear to provide good numerical accuracy compared to higher resolutions.
      The multigrid iteration typically converges in less than ten iterations
      independent of the grid resolution. Even without parallelization, each iteration
      takes about 1.0 s or 0.1 s for the 1 and 2 mm resolutions, respectively. This
      suggests that calculating the electric field with sufficient accuracy in real
      time is feasible.

PMID- 23128378
TI  - Cationic liposome-mediated nitric oxide synthase gene therapy enhances the
      antitumor effects of cisplatin in lung cancer.
AB  - Cisplatin is one of the most effective antitumor drugs for non-small cell lung
      carcinoma (NSCLC) patients. However, its efficacy has encountered a plateau due
      to its side effects and drug resistance. Inducible nitric oxide (NO) synthase
      (iNOS) gene therapy has been reported to have antitumor effects in several types
      of cancers and enhances sensitivity to cisplatin, but the effects of iNOS gene
      therapy alone or its combination with cisplatin in lung cancer remain unclear. In
      the current study, we evaluated the effects of cationic liposome (LP)-mediated
      iNOS gene transfection on enhancing low-dose cisplatin-mediated antitumor effects
      in the A549 human lung adenocarcinoma cell line in vitro. Furthermore, we
      examined whether iNOS gene therapy enhances the antitumor effects of low-dose
      cisplatin in two A549 human lung cancer cell xenograft mouse models. The results
      revealed that iNOS gene therapy may significantly enhance low-dose cisplatin
      mediated inhibition of cell proliferation, invasion, migration and promotion of
      cell apoptosis in A549 cells. Intratumoral administration of the LP-pVAX-iNOS
      complex significantly enhanced low-dose cisplatin-mediated suppression of
      subcutaneous tumor growth. Moreover, intravenous injection of the LP-pVAX-iNOS
      complex greatly enhanced low-dose cisplatin-mediated inhibition of experimental
      lung metastasis and prolonged the life span of mice without significant organ
      related toxicity in a nude mouse model of lung metastasis compared to the
      cisplatin alone-treated group. Furthermore, iNOS gene-mediated enhancement of
      cisplatin-mediated antitumor effects in lung cancer may be related to the
      attenuation of p-mTOR, MMP2 and the activation of p-p53. Thus, the combination
      treatment with iNOS gene therapy and cisplatin may be a novel and effective
      therapeutic strategy for lung cancer.

PMID- 23128379
TI  - Practical course on "imaging infection: from single molecules to animals".
AB  - A 2-week long theoretical and practical course on innovative microscopy in the
      field of microbial infection was organized in Pretoria, South Africa. Talks from
      lecturers from such fields as super-resolution microscopy, fluorescence and
      bioluminescence imaging, high throughput microscopy assays and image analysis
      were followed by practicals on cutting-edge microscopes.

PMID- 23128380
TI  - The role of omega-3 fatty acid supplemented parenteral nutrition in critical
      illness in adults: a systematic review and meta-analysis.
AB  - OBJECTIVE: To determine whether the supplementation of parenteral nutrition with
      omega-3 fatty acids confers treatment benefits to critically ill adult patients.
      DATA SOURCE: We performed computerized searches for relevant articles from 1996
      to June 2011 on MEDLINE, EMBASE, and the Cochrane register of controlled trials
      and abstracts of scientific meetings from 2005 to 2011. STUDY SELECTION:
      Randomized controlled trials of omega-3 fatty acid supplemented parenteral
      nutrition in critically ill adult patients admitted to the intensive therapy
      unit, given in addition to their routine care, compared with parenteral nutrition
      without omega-3 fatty acid supplementation. DATA SYNTHESIS: Five fully published
      trials and three trials published in abstract form with 391 participants have
      been included. Overall trial quality was poor. Mortality data were pooled from
      eight studies with 391 participants. No differences were found with a risk ratio
      for death of 0.83 (95% confidence interval 0.57, 1.20; p = 0.32). Data for
      infectious complications were available from five studies with 337 participants.
      No differences were found, with a risk ratio for infection of 0.78 (95%
      confidence interval 0.43, 1.41; p = 0.41). Data for intensive therapy unit and
      hospital length of stay were available from six and three studies with 305 and
      117 participants, respectively. With respect to intensive therapy unit length of
      stay, no differences were observed with a mean difference of 0.57 days in favor
      of the omega-3 fatty acid group (95% confidence interval -5.05, 3.90; p = 0.80).
      A significant reduction in hospital length of stay of 9.49 days (95% confidence
      interval -16.51, -2.47; p = 0.008) was observed for those receiving omega-3 fatty
      acid supplemented parenteral nutrition, but results were strongly influenced by
      one small study. CONCLUSIONS: On the basis of this systematic review, it can be
      concluded that omega-3 fatty acid supplementation of parenteral nutrition does
      not improve mortality, infectious complications, and intensive therapy unit
      length of stay in comparison with standard parenteral nutrition. Although omega-3
      fatty acids appear to reduce hospital length of stay, the poor methodology of the
      included studies and the absence of other outcome improvements mean they cannot
      be presently recommended.

PMID- 23128381
TI  - The association between ICU readmission rate and patient outcomes.
AB  - OBJECTIVE: To examine the association between ICU readmission rates and case-mix
      adjusted outcomes. DESIGN: Retrospective cohort study of ICU admissions from 2002
      to 2010. SETTING: One hundred five ICUs at 46 United States hospitals. PATIENTS:
      Of 369,129 admissions, 263,082 were first admissions that were alive at ICU
      discharge and candidates for readmission. INTERVENTIONS: None. MEASUREMENTS AND
      MAIN RESULTS: The median unit readmission rate was 5.9% (intraquartile range 5.1%
      7.0%). Across all admissions, hospital mortality for patients with and without
      readmission was 21.3% vs. 3.6%, mean ICU stay 4.9 days vs. 3.4 days, and hospital
      stay 13.3 days vs. 4.5 days, respectively. We stratified ICUs according to their
      readmission rate: high (>7%), moderate (5%-7%), and low (<5%) rates. Observed and
      case-mix-adjusted hospital mortality, ICU and hospital lengths of stay were
      examined by readmission rate strata. Observed outcomes were much worse in the
      high readmission rate units. But after adjusting for patient and institutional
      differences, there was no association between level of unit readmission rate and
      case-mix-adjusted mortality. The difference between observed and predicted
      mortality was -0.4%, 0.4%, and -1.1%, for the high, medium, and low readmission
      rate strata, respectively. Additionally, the difference between observed and
      expected ICU length of stay was approximately zero for the three strata.
      CONCLUSIONS: Patients readmitted to ICUs have increased hospital mortality and
      lengths of stay. After case-mix adjustment, there were no significant differences
      in standardized mortality or case-mix-adjusted lengths of stay between units with
      high readmission rates compared to units with moderate or low rates. The use of
      readmission as a quality measure should only be implemented if patient case-mix
      is taken into account.

PMID- 23128382
TI  - Cardiac output response to norepinephrine in postoperative cardiac surgery
      patients: interpretation with venous return and cardiac function curves.
AB  - OBJECTIVE: We studied the variable effects of norepinephrine infusion on cardiac
      output in postoperative cardiac surgical patients in whom norepinephrine
      increased mean arterial pressure. We hypothesized that the directional change in
      cardiac output would be determined by baseline cardiac function, as quantified by
      stroke volume variation, and the subsequent changes in mean systemic filling
      pressure and vasomotor tone. DESIGN: Intervention study. SETTING: ICU of a
      university hospital. PATIENTS: Sixteen mechanically ventilated postoperative
      cardiac surgery patients. INTERVENTIONS: Inspiratory holds were performed at
      baseline-1, during increased norepinephrine infusion, and baseline-2 conditions.
      MEASUREMENTS AND MAIN RESULTS: We measured mean arterial pressure, heart rate,
      central venous pressure, cardiac output, stroke volume variation and, with use of
      inspiratory hold maneuvers, mean systemic filling pressure, then calculated
      resistance for venous return and systemic vascular resistance. Increasing
      norepinephrine by 0.04 +/- 0.02 MUg.kg.min increased mean arterial pressure 20 mm
      Hg in all patients. Cardiac output decreased in ten and increased in six
      patients. In all patients mean systemic filling pressure, systemic vascular
      resistance and resistance for venous return increased and stroke volume variation
      decreased. Resistance for venous return and systemic vascular resistance
      increased more (p = 0.019 and p = 0.002) in the patients with a cardiac output
      decrease. Heart rate decreased in the patients with a cardiac output decrease (p
      = 0.002) and was unchanged in the patients with a cardiac output increase.
      Baseline stroke volume variation was higher in those in whom cardiac output
      increased (14.4 +/- 4.2% vs. 9.1 +/- 2.4%, p = 0.012). Stroke volume variation
      >8.7% predicted the increase in cardiac output to norepinephrine (area under the
      receiver operating characteristic curve 0.900). CONCLUSIONS: The change in
      cardiac output induced by norepinephrine is determined by the balance of volume
      recruitment (increase in mean systemic filling pressure), change in resistance
      for venous return, and baseline heart function. Furthermore, the response of
      cardiac output on norepinephrine can be predicted by baseline stroke volume
      variation.

PMID- 23128383
TI  - Fluctuations in serum sodium level are associated with an increased risk of death
      in surgical ICU patients.
AB  - OBJECTIVE: Dysnatremia may have an impact on outcomes in critically ill patients,
      but this has not been widely investigated in surgical ICU patients. We
      investigated the epidemiology of dysnatremia in a large cohort of surgical ICU
      patients and evaluated the possible influence of the time of acquisition of
      dysnatremia and fluctuations in serum sodium concentrations on hospital mortality
      in these patients. DESIGN: Retrospective analysis. SETTING: Fifty-bed surgical
      ICU. PATIENTS: All patients admitted to the ICU between January 2004 and January
      2009. MEASUREMENTS AND MAIN RESULTS: Hyponatremia was defined as a serum sodium
      concentration <135 mmol/L and hypernatremia as a serum sodium concentration >145
      mmol/L. Of the 10,923 surgical ICU patients included in the study, 1,215 (11.2%)
      had hyponatremia and 277 (2.5%) had hypernatremia at admission to the ICU. Among
      patients with normonatremia at admission to the ICU (n = 9431), the prevalence of
      ICU-acquired dysnatremia was 31.3%. Dysnatremia present at ICU admission (odds
      ratio 2.53; 95% confidence interval 2.06-3.12; p < .001) and ICU-acquired
      dysnatremia (odds ratio 2.06; 95% confidence interval 1.71-2.48; p < 0.001) were
      independently associated with an increased risk of in-hospital death compared to
      normonatremia. Dysnatremia at ICU admission (odds ratio 1.23; 95% confidence
      interval 1.01-1.50) was associated with a higher risk of in-hospital death,
      compared with ICU-acquired dysnatremia. Fluctuation in serum sodium concentration
      was also independently associated with an increased risk of in-hospital
      mortality, in patients who remained normonatremic (>6 mmol/L/ICU stay) and in
      those with dysnatremia (>12 mmol/L/24 hrs or >12 mmol/L/ICU stay). CONCLUSIONS:
      Dysnatremia was common in surgical ICU patients and was independently associated
      with an increased risk of in-hospital death in these patients. Dysnatremia at ICU
      admission was associated with a higher risk of death compared with ICU-acquired
      dysnatremia. Fluctuations in serum sodium concentrations were independently
      associated with an increased risk of in-hospital death, even in patients who
      remained normonatremic during the ICU stay.

PMID- 23128384
TI  - An in vitro model of mycobacterial granuloma to investigate the immune response
      in brain-injured patients.
AB  - OBJECTIVE: We investigated the overall immune response to pathogens in brain
      injured patients, and assessed its relationship to nosocomial pneumonia. DESIGN:
      Observational study. SETTING: Two surgical ICUs of a single institution.
      PATIENTS: Severe brain-injured patients (n = 32) requiring mechanical ventilation
      and sex- and age-matched healthy donors (n = 25). INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: We evaluated, ex vivo, the ability of peripheral
      blood mononuclear cells from brain injury patients to develop an effective
      granulomatous response to mycobacteria. Thirty-two consecutive patients (25
      traumatic brain injured and seven subarachnoid hemorrhage) were included. Median
      Glasgow Coma Scale was 7 (5-8). Thirteen (41%) patients developed nosocomial
      pneumonia. Peripheral blood mononuclear cells from brain-injured patients with
      nosocomial pneumonia generated significantly fewer mature granulomas compared
      with brain-injured patients without nosocomial pneumonia and with healthy donors.
      The percentage of multinucleated giant cells was lower in brain-injured patients
      without nosocomial pneumonia (1% [range: 0%-7%]) and in brain-injured patients
      with nosocomial pneumonia (4% [range: 2%-5%]) compared with healthy donors (20%
      [range: 15%-28%]). The blood levels of gammadelta T cells were significantly
      increased in brain-injured patients without nosocomial pneumonia (66% [range: 34%
      69%]) compared with healthy donors (23% [range: 8%-61%]) and was not altered in
      brain-injured patients with nosocomial pneumonia (31% [range: 12%-44%]). The
      percentage of gammadelta T cells in granulomas was significantly decreased in
      brain injury patients with nosocomial pneumonia (5% [range: 4%-43%]) compared
      with healthy donors (43% [range: 19%-54%]) and was not significantly altered in
      brain-injured patients without nosocomial pneumonia (26% [range: 10%-41%]). The
      blood levels of natural killer cells were not altered in brain-injured patients.
      The percentage of natural killer cells in granulomas was significantly decreased
      in brain-injured patients with nosocomial pneumonia (3% [range: 1%-9%]) compared
      with brain-injured patients without nosocomial pneumonia (16% [range: 6%-29%])
      and with healthy donors (17% [range: 10%-29%]). CONCLUSIONS: Brain-injured
      patients experienced a maturation defect of the ex vivo granulomatous response
      involving monocytes as well as natural killer cells and gammadelta T cells.

PMID- 23128385
TI  - Dissociation of inflammatory mediators and function: experimental lung injury in
      nonpulmonary sepsis.
AB  - BACKGROUND: Sepsis is a common indication for mechanical ventilation, which, with
      higher tidal volume, can cause ventilator-associated lung injury. Inflammatory
      mediators in the plasma or bronchoalveolar fluid are sometimes proposed as
      biomarkers in ICU patients. OBJECTIVE: To test the hypothesis that "priming" with
      subthreshold sepsis in a clinically relevant model would worsen lung function,
      increase ventilator-induced mediator production, and differentially impact
      systemic vs. pulmonary mediator levels. The model used was cecal ligation and
      perforation modified so that alone it caused lung inflammatory responses but not
      injury. METHODS AND MAIN RESULTS: Anesthetized mice were randomized to cecal
      ligation and perforation (vs. sham) with or without dexamethasone and 6 hrs later
      further randomized to: 1) sham, nonventilated, saline; 2) cecal ligation and
      perforation, nonventilated, saline; 3) cecal ligation and perforation,
      nonventilated, dexamethasone; 4) sham, high tidal volume, saline; 5) sham, high
      tidal volume, dexamethasone; 6) cecal ligation and perforation, high tidal
      volume, saline; or 7) cecal ligation and perforation, high tidal volume,
      dexamethasone. Mediators associated with sepsis and lung injury (cytokines:
      interleukin-6, tumor necrosis factor-alpha; chemokine: keratinocyte stimulating
      factor) were measured in the plasma and the bronchoalveolar lavage, and lung
      function (compliance, oxygenation, alveolar protein leak) assessed. High tidal
      volume and cecal ligation and perforation increased individual bronchoalveolar
      lavage and plasma mediators; high tidal volume but not cecal ligation and
      perforation impaired lung function. Priming of high tidal volume by cecal
      ligation and perforation intensified plasma and bronchoalveolar lavage mediators;
      the plasma (but not the bronchoalveolar lavage) mediators were inhibited by
      dexamethasone pretreatment. CONCLUSIONS: Mediator-but not functional-responses to
      high tidal volume are augmented by subthreshold sepsis priming. There is
      important discordance among systemic and pulmonary mediators, physiologic
      function, and response to corticosteroids; thus, mediator levels may be
      incomplete surrogates for measures of lung injury or response to therapy in the
      context of systemic sepsis.

PMID- 23128386
TI  - De novo chemoenzymatic synthesis of sialic acid.
AB  - A chemoenzymatic synthesis of sialic acid from inexpensive N-acetyl-D-glucosamine
      is described. In a three-step Wittig-protection-ozonolysis strategy manno
      configured aldehydes are obtained. Treatment with oxaloacetate in the presence of
      macrophomate synthase affords the signature alpha-keto-gamma-hydroxy acid moiety
      with high diastereoselectivity.

PMID- 23128387
TI  - Outcome comparison of atlantoaxial fusion with transarticular screws and screw
      rod constructs: meta-analysis and review of literature.
AB  - STUDY DESIGN: Literature review and meta-analysis. OBJECTIVE: To compare clinical
      and radiographic outcomes of patients treated with transarticular screws (TASs)
      and screw-rod constructs (SRCs) for posterior atlantoaxial fusion. BACKGROUND:
      Modern techniques for C1-C2 fusions include Magerl and Seeman's TAS and SRC using
      C1 lateral mass screws and C2 pars/pedicle screws as described by Goel and Laheri
      and later modified by Harms and Melcher. MATERIALS AND METHODS: Online databases
      were searched for English-language articles between 1986 and April 2011
      describing posterior atlantoaxial instrumentation with C1-C2 TAS or SRC. Forty
      five studies (2073 patients) treated with TAS and 24 studies (1073 patients)
      treated with SRC fulfilled inclusion criteria. Standard and formal meta-analysis
      techniques were used to compare the outcomes. RESULTS: All studies provided class
      III evidence. There were no differences in 30-day mortality (0.8% vs. 0.6%) or
      neurological injury (0.2% vs. 0%). There was a higher incidence of vertebral
      artery injury [4.1% (95% confidence interval (CI), 2.8%-5.4%) vs. 2.0% (95% CI,
      1.1%-3.4%); P=0.02] and malpositioned screws [7.1% (95% CI, 5.7%-8.8%) vs. 2.4%
      (95% CI, 1.1%-4.1%); P<0.001] and a slightly lower rate of fusion with the TAS
      technique [97.5% (95% CI, 95.9%-98.5%) vs. 94.6% (95% CI, 92.6%-96.1%); P<0.001].
      CONCLUSIONS: TAS and SRC are safe and effective treatment options for C1-C2
      instability but require a thorough knowledge of atlantoaxial anatomy for
      successful insertion of screws. Slightly higher rates of fusion and less risk of
      injury to the vertebral artery during screw placement were observed with the SRC
      technique. However, differences in graft material and techniques were noted.
      Prospective, randomized studies with validated radiographic and clinical outcome
      metrics are necessary for proper comparison of these techniques.

PMID- 23128388
TI  - Pretreatment viral DNA stratifies mortality risk in patients receiving antiviral
      therapy for severe acute exacerbation of chronic hepatitis B.
AB  - BACKGROUND: Prognostic factors have not been elucidated for severe acute
      exacerbation of chronic hepatitis B treated with antiviral therapy. This study
      aimed to explore the role of baseline viral load in predicting mortality.
      METHODS: This retrospective cohort study screened consecutive chronic hepatitis B
      patients (n=84) receiving antiviral therapy for severe acute exacerbation,
      defined as abrupt elevation of serum alanine aminotransferase >10* the upper
      limit of normal along with hyperbilirubinaemia. Survival pattern was evaluated by
      the Kaplan-Meier method and predictors for mortality determined by the Cox
      regression analysis. RESULTS: A total of 66 patients were eligible and followed
      up for a median of 23 months (range 0.1-75.0). Overall, 20 (30.3%) patients died
      during the study period, with the vast majority (n=17) succumbing rapidly within
      3 months of severe acute exacerbation. The multivariate Cox model revealed that
      mortality was associated with baseline viral DNA level (HR 1.49 per log
      copies/ml, 95% CI 1.13, 1.96), international normalized ratio for prothrombin
      time (HR 2.68 per unit, 95% CI 1.81, 3.98), platelet count (HR 0.87 per 10(4)
      cells/MUl, 95% CI 0.78, 0.98) and age (HR 1.10 per year, 95% CI 1.05, 1.15). A
      significant interaction existed between viral DNA and prolonged prothrombin time
      (P=0.005). Stratified analyses further demonstrated that pronounced coagulopathy
      heralded death irrespective of viral load, whereas serum level of viral DNA
      stratified mortality risk among those without marked coagulopathy. CONCLUSIONS:
      Pretreatment viral DNA level stratifies risk of death in patients with severe
      acute exacerbation of chronic hepatitis B before the manifestation of overt liver
      failure.

PMID- 23128389
TI  - SLK-mediated phosphorylation of paxillin is required for focal adhesion turnover
      and cell migration.
AB  - Focal adhesion turnover is a complex process required for cell migration. We have
      previously shown that the Ste20-like kinase (SLK) is required for cell migration
      and efficient focal adhesion (FA) turnover in a FA kinase (FAK)-dependent manner.
      However, the role of SLK in this process remains unclear. Using a candidate
      substrate approach, we show that SLK phosphorylates the adhesion adapter protein
      paxillin on serine 250. Serine 250 phosphorylation is required for paxillin
      redistribution and cell motility. Mutation of paxillin serine 250 prevents its
      phosphorylation by SLK in vitro and results in impaired migration in vivo as
      evidenced by an accumulation of phospho-FAK-Tyr397 and altered FA turnover rates.
      Together, our data suggest that SLK phosphorylation of paxillin on serine 250 is
      required for FAK-dependent FA dynamics. 

PMID- 23128390
TI  - CpG island shore methylation regulates caveolin-1 expression in breast cancer.
AB  - Caveolin-1 (Cav1) is an integral membrane, scaffolding protein found in plasma
      membrane invaginations (caveolae). Cav1 regulates multiple cancer-associated
      processes. In breast cancer, a tumor suppressive role for Cav1 has been
      suggested; however, Cav1 is frequently overexpressed in aggressive breast cancer
      subtypes, suggesting an oncogenic function in advanced-stage disease. To further
      delineate Cav1 function in breast cancer progression, we evaluated its expression
      levels among a panel of cell lines representing a spectrum of breast cancer
      phenotypes. In basal-like (the most aggressive BC subtype) breast cancer cells,
      Cav1 was consistently upregulated, and positively correlated with increased cell
      proliferation, anchorage-independent growth, and migration and invasion. To
      identify mechanisms of Cav1 gene regulation, we compared DNA methylation levels
      within promoter 'CpG islands' (CGIs) with 'CGI shores', recently described
      regions that flank CGIs with less CG-density. Integration of genome-wide DNA
      methylation profiles ('methylomes') with Cav1 expression in 30 breast cancer cell
      lines showed that differential methylation of CGI shores, but not CGIs,
      significantly regulated Cav1 expression. In breast cancer cell lines having low
      Cav1 expression (despite promoter CGI hypomethylation), we found that treatment
      with a DNA methyltransferase inhibitor induced Cav1 expression via CGI shore
      demethylation. In addition, further methylome assessments revealed that breast
      cancer aggressiveness associated with Cav1 CGI shore methylation levels, with
      shore hypermethylation in minimally aggressive, luminal breast cancer cells and
      shore hypomethylation in highly aggressive, basal-like cells. Cav1 CGI shore
      methylation was also observed in human breast tumors, and overall survival rates
      of breast cancer patients lacking estrogen receptor alpha (ERalpha) negatively
      correlated with Cav1 expression. Based on this first study of Cav1 (a potential
      oncogene) CGI shore methylation, we suggest this phenomenon may represent a new
      prognostic marker for ERalpha-negative, basal-like breast cancer. 

PMID- 23128391
TI  - Novel BRD4-NUT fusion isoforms increase the pathogenic complexity in NUT midline
      carcinoma.
AB  - Nuclear protein in testis (NUT)-midline carcinoma (NMC) is a rare, aggressive
      disease typically presenting with a single t(15;19) translocation that results in
      the generation of a bromodomain-containing protein 4 (BRD4)-NUT fusion. PER-624
      is a cell line generated from an NMC patient with an unusually complex karyotype
      that gave no initial indication of the involvement of the NUT locus. Analysis of
      PER-624 next-generation transcriptome sequencing (RNA-Seq) using the algorithm
      FusionFinder identified a novel transcript in which Exon 15 of BRD4 was fused to
      Exon 2 of NUT, therefore differing from all published NMC fusion transcripts. The
      three additional exons contained in the PER-624 fusion encode a series of
      polyproline repeats, with one predicted to form a helix. In the NMC cell line PER
      403, we identified the 'standard' NMC fusion and two novel isoforms. Knockdown by
      small interfering RNA in either cell line resulted in decreased proliferation,
      increased cell size and expression of cytokeratins consistent with epithelial
      differentiation. These data demonstrate that the novel BRD4-NUT fusion in PER-624
      encodes a functional protein that is central to the oncogenic mechanism in these
      cells. Genomic PCR indicated that in both PER-624 and PER-403, the translocation
      fuses an intron of BRD4 to a region upstream of the NUT coding sequence. Thus,
      the generation of BRD4-NUT fusion transcripts through post-translocation RNA
      splicing appears to be a common feature of these carcinomas that has not
      previously been appreciated, with the mechanism facilitating the expression of
      alternative isoforms of the fusion. Finally, ectopic expression of wild-type NUT,
      a protein normally restricted to the testis, could be demonstrated in PER-403,
      indicating additional pathways for aberrant cell signaling in NMC. This study
      contributes to our understanding of the genetic diversity of NMC, an important
      step towards finding therapeutic targets for a disease that is refractory to
      current treatments. 

PMID- 23128392
TI  - Mitochondrial dynamics regulates migration and invasion of breast cancer cells.
AB  - Mitochondria are highly dynamic and undergo constant fusion and fission that are
      essential for maintaining physiological functions of cells. Although dysfunction
      of mitochondria has been implicated in tumorigenesis, little is known about the
      roles of mitochondrial dynamics in metastasis, the major cause of cancer death.
      In the present study, we found a marked upregulation of mitochondrial fission
      protein dynamin-related protein 1 (Drp1) expression in human invasive breast
      carcinoma and metastases to lymph nodes. Compared with non-metastatic breast
      cancer cells, mitochondria also were more fragmented in metastatic breast cancer
      cells that express higher levels of total and active Drp1 and less mitochondrial
      fusion protein 1 (Mfn1). Silencing Drp1 or overexpression of Mfn1 resulted in
      mitochondria elongation or clusters, respectively, and significantly suppressed
      metastatic abilities of breast cancer cells. In contrast, silencing Mfn proteins
      led to mitochondrial fragmentation and enhanced metastatic abilities of breast
      cancer cells. Interestingly, these manipulations of mitochondrial dynamics
      altered the subcellular distribution of mitochondria in breast cancer cells. For
      example, silencing Drp1 or overexpression of Mfn1 inhibited lamellipodia
      formation, a key step for cancer metastasis, and suppressed chemoattractant
      induced recruitment of mitochondria to lamellipodial regions. Conversely,
      silencing Mfn proteins resulted in more cell spreading and lamellipodia
      formation, causing accumulation of more mitochondria in lamellipodia regions.
      More importantly, treatment with a mitochondrial uncoupling agent or adenosine
      triphosphate synthesis inhibitor reduced lamellipodia formation and decreased
      breast cancer cell migration and invasion, suggesting a functional importance of
      mitochondria in breast cancer metastasis. Together, our findings show a new role
      and mechanism for regulation of cancer cell migration and invasion by
      mitochondrial dynamics. Thus targeting dysregulated Drp1-dependent mitochondrial
      fission may provide a novel strategy for suppressing breast cancer metastasis. 

PMID- 23128393
TI  - TAF15 is important for cellular proliferation and regulates the expression of a
      subset of cell cycle genes through miRNAs.
AB  - TAF15 (formerly TAFII68) is a member of the FET (FUS, EWS, TAF15) family of RNA-
      and DNA-binding proteins whose genes are frequently translocated in sarcomas. By
      performing global gene expression profiling, we found that TAF15 knockdown
      affects the expression of a large subset of genes, of which a significant
      percentage is involved in cell cycle and cell death. In agreement, TAF15
      depletion had a growth-inhibitory effect and resulted in increased apoptosis.
      Among the TAF15-regulated genes, targets of microRNAs (miRNAs) generated from the
      onco-miR-17 locus were overrepresented, with CDKN1A/p21 being the top miRNAs
      targeted gene. Interestingly, the levels of onco-miR-17 locus coded miRNAs (miR
      17-5p and miR-20a) were decreased upon TAF15 depletion and shown to affect the
      post-transcriptional regulation of TAF15-dependent genes, such as CDKN1A/p21.
      Thus, our results demonstrate that TAF15 is required to regulate gene expression
      of cell cycle regulatory genes post-transcriptionally through a pathway involving
      miRNAs. The findings that high TAF15 levels are needed for rapid cellular
      proliferation and that endogenous TAF15 levels decrease during differentiation
      strongly suggest that TAF15 is a key regulator of maintaining a highly
      proliferative rate of cellular homeostasis. 

PMID- 23128394
TI  - Analysis of the combined action of miR-143 and miR-145 on oncogenic pathways in
      colorectal cancer cells reveals a coordinate program of gene repression.
AB  - MicroRNAs (miRNAs) from the gene cluster miR-143-145 are diminished in cells of
      colorectal tumor origin when compared with normal colon epithelia. Until now, no
      report has addressed the coordinate action of these miRNAs in colorectal cancer
      (CRC). In this study, we performed a comprehensive molecular and functional
      analysis of the miRNA cluster regulatory network. First, we evaluated
      proliferation, migration, anchorage-independent growth and chemoresistance in the
      colon tumor cell lines after miR-143 and miR-145 restoration. Then, we assessed
      the contribution of single genes targeted by miR-143 and miR-145 by reinforcing
      their expression and checking functional recovery. Restoring miR-143 and miR-145
      in colon cancer cells decreases proliferation, migration and chemoresistance. We
      identified cluster of differentiation 44 (CD44), Kruppel-like factor 5 (KLF5),
      Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) and v-Raf murine sarcoma
      viral oncogene homolog B1 (BRAF) as proteins targeted by miR-143 and miR-145.
      Their re-expression can partially revert a decrease in transformation properties
      caused by the overexpression of miR-143 and miR-145. In addition, we determined a
      set of mRNAs that are diminished after reinforcing miR-143 and miR-145
      expression. The whole transcriptome analysis ascertained that downregulated
      transcripts are enriched in predicted target genes in a statistically significant
      manner. A number of additional genes, whose expression decreases as a direct or
      indirect consequence of miR-143 and miR-145, reveals a complex regulatory network
      that affects cell signaling pathways involved in transformation. In conclusion,
      we identified a coordinated program of gene repression by miR-143 and miR-145, in
      CRC, where either of the two miRNAs share a target transcript, or where the
      target transcripts share a common signaling pathway. Major mediators of the
      oncosuppression by miR-143 and miR-145 are genes belonging to the growth factor
      receptor-mitogen-activated protein kinase network and to the p53 signaling
      pathway. 

PMID- 23128395
TI  - RAD001 (everolimus) induces dose-dependent changes to cell cycle regulation and
      modifies the cell cycle response to vincristine.
AB  - More than 50% of adults and ~20% of children with pre-B acute lymphoblastic
      leukemia (ALL) relapse following treatment. Dismal outcomes for patients with
      relapsed or refractory disease mandate novel approaches to therapy. We have
      previously shown that the combination of the mTOR inhibitor RAD001 (everolimus)
      and the chemotherapeutic agent vincristine increases the survival of non-obese
      diabetic/severe combined immuno-deficient (NOD/SCID) mice bearing human ALL
      xenografts. We have also shown that 16 MUM RAD001 synergized with agents that
      cause DNA damage or microtubule disruption in pre-B ALL cells in vitro. Here, we
      demonstrate that RAD001 has dose-dependent effects on the cell cycle in ALL
      cells, with 1.5 MUM RAD001 inhibiting pRb, Ki67 and PCNA expression and
      increasing G0/1 cell cycle arrest, whereas 16 MUM RAD001 increases pRb, cyclin
      D1, Ki67 and PCNA, with no evidence of an accumulation of cells in G0/1.
      Transition from G2 into mitosis was promoted by 16 MUM RAD001 with reduced
      phosphorylation of cdc2 in cells with 4 N DNA content. However, 16 MUM RAD001
      preferentially induced cell death in cells undergoing mitosis. When combined with
      vincristine, 16 MUM RAD001 reduced the vincristine-induced accumulation of cells
      in mitosis, probably as a result of increased death in this population. Although
      16 MUM RAD001 weakly activated Chk1 and Chk2, it suppressed strong vincristine
      induced activation of these cell cycle checkpoint regulators. We conclude that
      RAD001 enhances chemosensitivity at least in part through suppression of cell
      cycle checkpoint regulation in response to vincristine and increased progression
      from G2 into mitosis.

PMID- 23128396
TI  - PIR2/Rnf144B regulates epithelial homeostasis by mediating degradation of p21WAF1
      and p63.
AB  - DeltaNp63 is a transcription factor that is critical for the development of
      stratified epithelia and is overexpressed or amplified in >80% of squamous cell
      carcinomas (SCCs). We identified the RING finger E3 ubiquitin ligase PIR2/Rnf144b
      as a direct transcriptional target of DeltaNp63alpha and showed that its
      expression parallels that of DeltaNp63alpha in keratinocytes, SCC cell lines and
      SCCs. We used primary keratinocytes as a model system to investigate the function
      of PIR2/Rnf144b in stratified epithelia. Depletion of PIR2/Rnf144b severely
      impaired keratinocyte proliferation and differentiation, associated with
      accumulation of p21(WAF1/CIP1); a known target of PIR2/Rnf144b. More importantly,
      we found that PIR2/Rnf144b binds and mediates proteasomal degradation of
      DeltaNp63alpha, generating a hitherto unknown auto-regulatory feedback loop.
      These findings substantiate PIR2/Rnf144b as a potentially critical component of
      epithelial homeostasis, acting downstream of DeltaNp63alpha to regulate cellular
      levels of p21(WAF1/CIP1) and DeltaNp63alpha. 

PMID- 23128397
TI  - Chromatin H3K27me3/H3K4me3 histone marks define gene sets in high-grade serous
      ovarian cancer that distinguish malignant, tumour-sustaining and chemo-resistant
      ovarian tumour cells.
AB  - In embryonic stem (ES) cells, bivalent chromatin domains containing H3K4me3 and
      H3K27me3 marks silence developmental genes, while keeping them poised for
      activation following differentiation. We have identified gene sets associated
      with H3K27me3 and H3K4me3 marks at transcription start sites in a high-grade
      ovarian serous tumour and examined their association with epigenetic silencing
      and malignant progression. This revealed novel silenced bivalent marked genes,
      not described previously for ES cells, which are significantly enriched for the
      PI3K (P<10(-7)) and TGF-beta signalling pathways (P<10(-5)). We matched histone
      marked gene sets to gene expression sets of eight normal fallopian tubes and 499
      high-grade serous malignant ovarian samples. This revealed a significant decrease
      in gene expression for the H3K27me3 and bivalent gene sets in malignant tissue.
      We then correlated H3K27me3 and bivalent gene sets to gene expression data of
      ovarian tumour 'stem cell-like' sustaining cells versus non-sustaining cells.
      This showed a significantly lower expression for the H3K27me3 and bivalent gene
      sets in the tumour-sustaining cells. Similarly, comparison of matched chemo
      sensitive and chemo-resistant ovarian cell lines showed a significantly lower
      expression of H3K27me3/bivalent marked genes in the chemo-resistant compared with
      the chemo-sensitive cell line. Our analysis supports the hypothesis that bivalent
      marks are associated with epigenetic silencing in ovarian cancer. However it also
      suggests that additional tumour specific bivalent marks, to those known in ES
      cells, are present in tumours and may potentially influence the subsequent
      development of drug resistance and tumour progression. 

PMID- 23128398
TI  - 3-dimensional resin casting and imaging of mouse portal vein or intrahepatic bile
      duct system.
AB  - In organs, the correct architecture of vascular and ductal structures is
      indispensable for proper physiological function, and the formation and
      maintenance of these structures is a highly regulated process. The analysis of
      these complex, 3-dimensional structures has greatly depended on either 2
      dimensional examination in section or on dye injection studies. These techniques,
      however, are not able to provide a complete and quantifiable representation of
      the ductal or vascular structures they are intended to elucidate. Alternatively,
      the nature of 3-dimensional plastic resin casts generates a permanent snapshot of
      the system and is a novel and widely useful technique for visualizing and
      quantifying 3-dimensional structures and networks. A crucial advantage of the
      resin casting system is the ability to determine the intact and connected, or
      communicating, structure of a blood vessel or duct. The structure of vascular and
      ductal networks are crucial for organ function, and this technique has the
      potential to aid study of vascular and ductal networks in several ways. Resin
      casting may be used to analyze normal morphology and functional architecture of a
      luminal structure, identify developmental morphogenetic changes, and uncover
      morphological differences in tissue architecture between normal and disease
      states. Previous work has utilized resin casting to study, for example,
      architectural and functional defects within the mouse intrahepatic bile duct
      system that were not reflected in 2-dimensional analysis of the structure(1,2),
      alterations in brain vasculature of a Alzheimer's disease mouse model(3), portal
      vein abnormalities in portal hypertensive and cirrhotic mice(4), developmental
      steps in rat lymphatic maturation between immature and adult lungs(5), immediate
      microvascular changes in the rat liver, pancreas, and kidney in response in to
      chemical injury(6). Here we present a method of generating a 3-dimensional resin
      cast of a mouse vascular or ductal network, focusing specifically on the portal
      vein and intrahepatic bile duct. These casts can be visualized by clearing or
      macerating the tissue and can then be analyzed. This technique can be applied to
      virtually any vascular or ductal system and would be directly applicable to any
      study inquiring into the development, function, maintenance, or injury of a 3
      dimensional ductal or vascular structure.

PMID- 23128399
TI  - Natalizumab: bench to bedside and beyond.
AB  - Natalizumab has been available as a multiple sclerosis treatment for more than 5
      years in Europe and the United States. Natalizumab was granted approval by the US
      Food and Drug Administration in 2004, only 12 years after its molecular target
      was cloned. Shortly after initial approval, natalizumab use was suspended pending
      a safety review when several natalizumab recipients were diagnosed as having
      progressive multifocal leukoencephalopathy. After the safety review, natalizumab
      was reintroduced to the market in 2006. Since then, more than 92,000 patients
      have been treated with the drug. Risk stratification algorithms and progressive
      multifocal leukoencephalopathy management strategies have been developed, which
      facilitate more personalized decision making and safer natalizumab use. This
      review article summarizes the evolution of natalizumab from target molecule
      discovery through regulatory approval, voluntary suspension, reapproval, and
      clinical use. The natalizumab story highlights both the opportunities and risks
      inherent in a novel biological therapy for a progressive neurologic disease.

PMID- 23128400
TI  - Methods for the evaluation of the protective efficacy of sunscreen products.
AB  - The objective of the present investigation was to examine the utilization of
      optical and spectroscopic methods for the noninvasive characterization of
      Anthelios XL Fluide Extreme (SPF 50+), an exemplary sunscreen, concerning its
      homogeneity of distribution on the skin, its spectroscopic properties and its
      overall protective efficacy. The homogeneity of the distribution of the sunscreen
      on the skin was investigated with a multiphoton tomography microscope.
      Additionally, the sum transmission spectrum was determined using tape stripping
      and spectroscopic measurements. The results revealed a very homogeneous
      distribution of the sunscreen on the skin surface and also in the deep furrows.
      The sum transmission spectrum reflects a high protective efficacy of the
      sunscreen in both the UVA and UVB ranges. The sunscreen Anthelios XL Fluide
      Extreme (SPF 50+) generates a comfortable feeling on the skin and can be easily
      distributed. The presented optical methods have been shown to be suitable to
      investigate the overall protective efficacy of sunscreen products objectively,
      noninvasively and quickly.

PMID- 23128401
TI  - Dermatosurgery: total quality management in a dermatology department.
AB  - BACKGROUND: Dermatosurgery (DS) is a growing sector in dermatology. Performance
      measurement is organized worldwide to improve the quality of health care.
      Clinical audit relies on self-assessment, comparison with guidelines, frames of
      references and implementation of improvement actions. OBJECTIVE: To assess the
      efficiency of our DS department. METHODS: A clinical audit focusing on the
      organization of the DS unit, patient routing, continuing medical education and
      training for students was conducted by two external auditors. After an initial
      evaluation, improvements were implemented and reassessed 1 year later by the same
      auditors. RESULTS: The audit resulted in the implementation of preoperative
      consultation, improved pre- and postoperative information leaflets for patients,
      standardizing of surgery reports, earmarking of funds for materials, and patient
      satisfaction survey. The training of residents was organized. CONCLUSION: This
      audit was a driving force for communication among the medical and paramedical
      teams and helped improve patient care and training of residents in DS. It also
      highlighted areas needing further improvement.

PMID- 23128402
TI  - Does 'cochlear Meniere's disease' exist? An electrocochleographic and audiometric
      study.
AB  - INTRODUCTION: According to current diagnostic criteria, patients exhibiting only
      cochlear symptoms without vertigo cannot be diagnosed with Meniere's disease
      (MD). The recently reported Meniere's Disease Index (MDI) combines audiometric
      and electrocochleographic parameters in a multidimensional measure correlating
      with the clinical degrees of MD. MATERIALS AND METHODS: Twenty-one patients with
      hearing loss, tinnitus and aural fullness, but without vertigo, underwent
      transtympanic electrocochleography. Based on the previously reported formula, the
      MDI value for every patient was calculated. RESULTS: Mean MDI value was 5.7 on a
      scale from 0 (mean value of non-MD patients) to 10 (mean value of definite MD
      patients). CONCLUSIONS: We can thus hypothesize that, based on audiometry and
      electrocochleography, 'cochlear MD' patients may represent a separate clinical
      entity with Meniere-like pathophysiology or underlying endolymphatic hydrops.

PMID- 23128404
TI  - Epidemiology and resistance mechanisms to imipenem in Klebsiella pneumoniae: a
      multicenter study.
AB  - Four clinical isolates of imipenem-resistant Klebsiella pneumoniae were isolated
      from clinical patient specimens and from samples obtained from hygienic
      surveillance in our hospital. We examined their minimum inhibitory concentration
      (MIC) to various types of antibiotics, detected the carbapenemases by a modified
      Hodge test and analyzed the genotype and homogeneity. The enzyme, Klebsiella
      pneumoniae carbapenemase (KPC)-2, was detected in all four isolates and this was
      the main cause of their imipenem resistance. In addition, these four isolates
      also contained the extended-spectrum beta-lactamase (ESBL) gene blaCTX-M-9 and
      the cephalosporinase (AmpC) gene blaDHA-1, which resulted in multidrug
      resistance. 

PMID- 23128403
TI  - Optimizing treatment switch for virologic failure during first-line
      antiretroviral therapy in resource-limited settings.
AB  - We evaluated adult Nigerian patients with antiretroviral switch to second-line
      treatment with ritonavir-boosted protease inhibitor (PI/r)-based regimens due to
      virologic failure (confirmed HIV-1 RNA viral load [VL] >1000 copies/mL) during
      first-line antiretroviral therapy. Proportion of patients with VL >400 copies/mL
      and characteristics associated with nonsuppression during second-line treatment
      are described. Approximately 15% of patients (34 of 225) had VL >400 copies/mL at
      1-year after treatment switch to PI/r-based regimens. In adjusted analyses, VL
      >=5 log10 copies/mL at treatment switch (odds ratio [OR] 2.90 [confidence
      interval (CI) 1.21-6.93]); duration of first-line treatment after virologic
      failure >180 days (OR 2.56 [CI 1.0-6.54]); and PI/r regimen adherence <90% (OR
      3.27 [CI 1.39-7.68]) were associated with VL >400 copies/mL at 1 year of second
      line treatment. We therefore recommend that the maximum permissible time between
      suspicion of virologic failure and completion of antiretroviral treatment switch
      should not exceed 6 months when patients develop first-line antiretroviral
      failure in resource-limited settings. 

PMID- 23128406
TI  - [About somatoform disorders].

PMID- 23128405
TI  - Cost-effectiveness of perioperative selective decontamination of the digestive
      tract versus placebo in elective gastrointestinal surgery.
AB  - OBJECTIVE: We compared the routine use of perioperative selective decontamination
      of the digestive tract (SDD) for elective gastrointestinal surgery with placebo
      in a randomized controlled trial. Alongside this trial, a cost-effectiveness
      analysis from a provider perspective was performed. METHODS AND RESULTS: A total
      of 289 patients undergoing elective surgery of the digestive tract were
      randomized to either SDD (143 patients) or placebo (146 patients). Routine use of
      SDD led to less patients with an infectious complication compared with placebo (p
      = 0.028). Mean total costs per patient were slightly less (EUR 2,604; 95% CI 
      6,292 to 1,084) in patients randomized to SDD (EUR 12,031) compared to patients
      randomized to placebo (EUR 14,635). Costs of hospitalization were the main
      determinant of the cost difference between the groups. The incremental cost
      effectiveness ratio per prevented occurrence of >=1 infectious complications per
      patient was -EUR 23,164, indicating the superiority of SDD over placebo.
      CONCLUSION: This study shows that in patients undergoing elective
      gastrointestinal surgery, the routine use of SDD is less expensive and
      economically more efficient than placebo in reducing the number of patients with
      infectious complications.

PMID- 23128407
TI  - [Personality disorders amongst inmates as a distorting factor in the prison
      social climate].
AB  - The prevalence of Personality Disorders (PD) in a prison and its effect on prison
      social climate are studied. Our research shows a statistically significant
      relationship between diagnosis of PD and indicators of social climate disruption
      such as aggressive interpersonal conduct or compulsive demand for psychoactive
      drugs in medical consultations. PD is one of the most common mental disorders in
      prison, and requires special attention from health services, while management of
      the disorder is a tremendously complex issue in the prison context.

PMID- 23128408
TI  - [A Methodologycal approach to the study of mental disorders in the prison
      population: The PreCa study].
AB  - This project aims to provide knowledge of reality in a psychiatric population
      neglected as the prison. The objectives of the study are: to estimate the
      prevalence of mental disorders in a Spanish prison sample, to analyze their
      association with sociodemographic and criminal as well as assess the impact on
      quality of life and describe and evaluate the health and social care received by
      People with mental disorders. Interviewing a total of 708 inmates sentenced to
      prison 5 distributed in 3 Autonomous Communities. Assessment instruments have
      been used SCID, IPDE, TONI II to assess the presence of mental disorders, quality
      of life scale (EuroQol and Social Weather CIES) and utlizacion service. RESULTS:
      The field project began in October 2006 to October 2007. There have been a total
      of 94,4% of planned interviews with results thar allow for data in the
      epidemiology of mental disorders in prison unprecedented so far.

PMID- 23128409
TI  - [Tuberculosis and its eponyms: Charles Mantoux (1877-1947)].
AB  - In 1908, Charles Mantoux, a French doctor perfected a test for the diagnosis of
      tuberculosis contact (latent tuberculosis). This study reviews the history of
      this technique, which is closely linked to the symbolism and mythology of an
      illness that at one time was known as the white plague.

PMID- 23128410
TI  - [Health care for prisoners with mental health problems in Holland].
AB  - In this study, a general picture is given of prisoners needing health care as a
      result of mental disorder and who, for this reason, have been interned in special
      care units with different security levels. Prisoners with mental disorders are an
      important factor in prisons in Holland. Services currently available for this
      type of inmate set out to offer the best care and support possible.

PMID- 23128411
TI  - [Cronica desafortunada de una lucha contra el sistema].

PMID- 23128412
TI  - Determination of the quenching correction factors for plastic scintillation
      detectors in therapeutic high-energy proton beams.
AB  - Plastic scintillation detectors (PSDs) have many advantages over other detectors
      in small field dosimetry due to their high spatial resolution, excellent water
      equivalence and instantaneous readout. However, in proton beams, the PSDs undergo
      a quenching effect which makes the signal level reduced significantly when the
      detector is close to the Bragg peak where the linear energy transfer (LET) for
      protons is very high. This study measures the quenching correction factor (QCF)
      for a PSD in clinical passive-scattering proton beams and investigates the
      feasibility of using PSDs in depth-dose measurements in proton beams. A
      polystyrene-based PSD (BCF-12, phi0.5 mm * 4 mm) was used to measure the depth
      dose curves in a water phantom for monoenergetic unmodulated proton beams of
      nominal energies 100, 180 and 250 MeV. A Markus plane-parallel ion chamber was
      also used to get the dose distributions for the same proton beams. From these
      results, the QCF as a function of depth was derived for these proton beams. Next,
      the LET depth distributions for these proton beams were calculated by using the
      MCNPX Monte Carlo code, based on the experimentally validated nozzle models for
      these passive-scattering proton beams. Then the relationship between the QCF and
      the proton LET could be derived as an empirical formula. Finally, the obtained
      empirical formula was applied to the PSD measurements to get the corrected depth
      dose curves and they were compared to the ion chamber measurements. A linear
      relationship between the QCF and LET, i.e. Birks' formula, was obtained for the
      proton beams studied. The result is in agreement with the literature. The PSD
      measurements after the quenching corrections agree with ion chamber measurements
      within 5%. PSDs are good dosimeters for proton beam measurement if the quenching
      effect is corrected appropriately.

PMID- 23128413
TI  - The flavonoid glabridin attenuates 2-deoxy-D-ribose-induced oxidative damage and
      cellular dysfunction in MC3T3-E1 osteoblastic cells.
AB  - Reducing sugar 2-deoxy-D-ribose (dRib) produces reactive oxygen species (ROS)
      through autoxidation and protein glycosylation and causes dysfunction of
      osteoblasts. In the present study, glabridin, a natural flavonoid, was
      investigated to determine whether it could influence dRib-induced oxidative
      damage and cellular dysfunction in the MC3T3-E1 mouse osteoblastic cell line.
      Osteoblastic cells were treated with dRib in the presence or absence of
      glabridin. Cell viability, apoptosis, ROS production and mitochondrial membrane
      potential (DeltaPsim) were subsequently examined. It was observed that dRib
      reduced cell survival and DeltaPsim, while it markedly increased intracellular
      levels of ROS and apoptosis. However, pretreatment of cells with glabridin
      attenuated all the dRib-induced effects. The antioxidant N-acetyl-L-cysteine
      (NAC) also prevented dRib-induced oxidative cell damage. In addition, treatment
      with glabridin resulted in a significant elevation of alkaline phosphatase (ALP)
      activity, collagen contents and osteoblast differentiation genes [ALP, collagen,
      osteopontin (OPN), osteoprotegerin (OPG) and osteocalcin (OC)] and bone
      morphogenetic protein (BMP) genes (BMP2, BMP4 and BMP7). In mechanistic studies
      of the antioxidative potential of glabridin, we found that glabridin activated
      dRib-induced decreased expression of phosphatidylinositol 3'-kinase (PI3K) and
      protein kinase B 2 (AKT2) genes, which are master regulators of survival-related
      signaling pathways. Glabridin also upregulated the gene expression of antioxidant
      enzymes, superoxide dismutase 1 (SOD1) and glutathione peroxidase 4 (GPX4), which
      were inhibited by dRib. Taken together, these results suggest that glabridin
      attenuates dRib-induced cell damage in osteoblastic cells and may be useful for
      the treatment of diabetes-related bone disease.

PMID- 23128414
TI  - Molecular cloning and heterologous expression of a true lipase in Pichia pastoris
      isolated via a metagenomic approach.
AB  - Lipases are important enzymes for various biotechnological applications. By using
      functional expression screening, lipZ03, a novel lipase gene, was isolated from a
      soil-derived metagenomic library. The gene was supposed to encode a protein of
      617 amino acids with a C-terminal targeting signal region and four potential N
      linked glycosylation sites. The protein sequence shared a conserved GXSXG motif
      (X represents any amino acid residue) with other microbial lipases. Gene lipZ03
      was expressed in Pichia pastoris and the molecular weight was estimated to be
      approximately 65 kDa by electrophoresis. The optimum reaction temperature and pH
      value for LipZ03 was 50 degrees C and 9.0, respectively. The enzyme was highly
      stable in the temperature range of 40-60 degrees C and under alkaline conditions
      (pH 8-10). Lipolytic activity was significantly enhanced by Ca(2+) and Mg(2+)
      ions, but dramatically inhibited by Cu(2+), Ni(2+) and Hg(2+) ions and EDTA. The
      purified enzyme preferentially hydrolyzed relatively long-chain triacylglycerols
      and was a true lipase rather than an esterase. Using a multi-stepwise methanol
      supply, the purified LipZ03 achieved a conversion yield of biodiesel production
      up to 74% after 36 h. Some interesting characteristics described here showed that
      the recombinant lipase may have potential to be a useful enzyme in industrial
      applications.

PMID- 23128415
TI  - Trend analysis of a tropical urban river water quality in Malaysia.
AB  - Rivers play a significant role in providing water resources for human and
      ecosystem survival and health. Hence, river water quality is an important
      parameter that must be preserved and monitored. As the state of Selangor and the
      city of Kuala Lumpur, Malaysia, are undergoing tremendous development, the river
      is subjected to pollution from point and non-point sources. The water quality of
      the Klang River basin, one of the most densely populated areas within the region,
      is significantly degraded due to human activities as well as urbanization.
      Evaluation of the overall river water quality status is normally represented by a
      water quality index (WQI), which consists of six parameters, namely dissolved
      oxygen, biochemical oxygen demand, chemical oxygen demand, suspended solids,
      ammoniacal nitrogen and pH. The objectives of this study are to assess the water
      quality status for this tropical, urban river and to establish the WQI trend.
      Using monthly WQI data from 1997 to 2007, time series were plotted and trend
      analysis was performed by employing the first-order autocorrelated trend model on
      the moving average values for every station. The initial and final values of
      either the moving average or the trend model were used as the estimates of the
      initial and final WQI at the stations. It was found that Klang River water
      quality has shown some improvement between 1997 and 2007. Water quality remains
      good in the upper stream area, which provides vital water sources for water
      treatment plants in the Klang valley. Meanwhile, the water quality has also
      improved in other stations. Results of the current study suggest that the present
      policy on managing river quality in the Klang River has produced encouraging
      results; the policy should, however, be further improved alongside more vigorous
      monitoring of pollution discharge from various point sources such as industrial
      wastewater, municipal sewers, wet markets, sand mining and landfills, as well as
      non-point sources such as agricultural or urban runoff and commercial activity.

PMID- 23128416
TI  - Gene networks: dissecting pathways in retinal development and disease.
AB  - During retinal neurogenesis, diverse cellular subtypes originate from multipotent
      neural progenitors in a spatiotemporal order leading to a highly specialized
      laminar structure combined with a distinct mosaic architecture. This is driven by
      the combinatorial action of transcription factors and signaling molecules which
      specify cell fate and differentiation. The emerging approach of gene network
      analysis has allowed a better understanding of the functional relationships
      between genes expressed in the developing retina. For instance, these gene
      networks have identified transcriptional hubs that have revealed potential
      targets and pathways for the development of therapeutic options for retinal
      diseases. Much of the current knowledge has been informed by targeted gene
      deletion experiments and gain-of-functional analysis. In this review we will
      provide an update on retinal development gene networks and address the wider
      implications for future disease therapeutics.

PMID- 23128418
TI  - Rhinosinusitis and asthma-microbiome and new perspectives.
AB  - PURPOSE OF REVIEW: Microbiome is one of the new perspectives in human health
      research, including airway diseases. There are several publications about the
      relationship of the microbiome and allergic diseases. Although pathogenesis of
      chronic rhinosinusitis (CRS) as well as its relationship with asthma has been
      widely investigated, the relationship of the microbiome and CRS is not yet well
      known. RECENT FINDINGS: The relationship between the hygiene hypothesis and
      microorganisms inside the human body and in the environment around it has been
      clearly shown. Furthermore, several researchers have reported that the
      microorganisms in the gut play a major role in regulating the immune cells that
      are of relevance to asthma and allergic diseases, such as Th1, Th2, Th17, Treg
      and dendritic cells as well as Toll-like receptors. Reduced contact of people
      with natural environmental features and biodiversity may adversely affect the
      human commensal microbiota and its immunomodulatory capacity.Some studies have
      shown a close relationship between CRS and Staphylococcus aureus, anaerobes and
      so on in the nasal cavity or paranasal sinuses, although the relationship between
      CRS and microorganisms in the gut has not been demonstrated. SUMMARY: In this
      review, we summarized about the microbiome, mainly in asthma and allergic
      diseases. The relationship between asthma and CRS has been clearly shown, and in
      particular, CRS with nasal polyps (CRSwNP) has been considered to be Th2
      dominant. Studies examining environmental microbial exposure in populations at
      risk for CRS are necessary to improve our understanding of the role this factor
      plays in disease development.

PMID- 23128419
TI  - Indoleamine 2,3-dioxygenase expression is associated with chronic rhinosinusitis:
      review of the evidence.
AB  - PURPOSE OF REVIEW: Indoleamine 2,3 dioxygenase (IDO), the key metabolic enzyme
      implicated in tryptophan catabolism has been studied extensively during the past
      years in cancer, infections and autoimmunity. This review summarizes the findings
      of the immunomodulatory effects of IDO. In addition, the possible role of IDO in
      chronic rhinosinusitis (CRS) is discussed. RECENT FINDINGS: Epithelial and
      leukocyte IDO expression is pronounced in CRS with nasal polyps and antrochoanal
      polyps. Although IDO associates with atopic disorders of the lower respiratory
      tract, we were not able to find an association between IDO and allergic rhinitis
      in the sinonasal mucosa. SUMMARY: IDO might have a distinct role in the upper and
      lower respiratory tract. Future studies need to identify whether the IDO found in
      sinonasal mucosa is active and if it is a cause or a reason in the development of
      CRS with nasal polyps.

PMID- 23128417
TI  - A contemporary concept of the blood-aqueous barrier.
AB  - This review traces the evolution of the concept of the blood-aqueous barrier
      (BAB) during the past 20 years. The Classical model simply stipulated that the
      tight junctions of the iris vasculature and ciliary epithelium excluded plasma
      proteins from the aqueous humor (AH). It failed to reconcile the presence of AH
      protein levels equal to 1% of that found in plasma. Moreover, models of barrier
      kinetics assumed that the processes of AH secretion and plasma protein entry were
      directly linked. Thus, elevations of AH protein levels could only be explained by
      a pathological breakdown of the BAB. Over the last 20 years it has been shown
      that the plasma proteins in normal AH by-pass the posterior chamber entirely.
      Instead, these proteins diffuse from the capillaries of ciliary body stroma, into
      the iris stroma and then into the anterior chamber. This creates a reservoir of
      plasma-proteins in the iris stroma that is not derived from the iris vessels.
      This reservoir is prevented from diffusing posteriorly by tight junctions in the
      posterior iris epithelium. The one-way valve created by the pupil resting on the
      anterior lens capsule, combined with the continuous, forward flow of AH through
      the pupil, prevents protein reflux into the posterior chamber. Importantly, in
      the new paradigm, secretion of AH and the entry of plasma proteins into AH, are
      semi-independent events. This opens the possibility that AH protein levels could
      increase in the absence of breakdown of the BAB. Clinical consequences of this
      new paradigm of the BAB are discussed.

PMID- 23128420
TI  - Amylose folding under the influence of lipids.
AB  - The molecular dynamics simulation technique was used to study the folding and
      complexation process of a short amylose fragment in the presence of lipids. In
      aqueous solution, the amylose chain remains as an extended left-handed helix.
      After the addition of lipids in the system, however, we observe spontaneous
      folding of the amylose chain into a helical structure, with helical pitch and
      hydrogen bond network compatible with the V-amylose structure observed in X-ray
      experiments. Our results suggest that under the influence of external non polar
      ligands, the conformation of amylose undergoes a transition from an extended to a
      V-amylose structure in line with experimental evidence.

PMID- 23128421
TI  - Premedication for intubation with morphine causes prolonged depression of
      electrocortical background activity in preterm infants.
AB  - BACKGROUND: Sedative and analgesic medications are used in critically ill
      newborns, but little is known about their effects on electrocortical activity in
      preterm infants. We hypothesized that morphine might induce prolonged
      neurodepression, independent of blood pressure, as compared with rapid sequence
      induction/intubation(RSI). METHODS: Of 34 infants enrolled in a randomized
      controlled trial (RCT) comparing RSI (including thiopental 2-3 mg/kg and
      remifentantil 1 mcg/kg) with morphine (0.3 mg/kg) as premedication for
      intubation, 28 infants (n = 14 + 14; median gestational age 26.1 wk and postnatal
      age 138 h) had continuous two-channel amplitude-integrated electroencephalogram
      (aEEG/EEG) and blood pressure monitoring during 24 h after the intubation.
      Thirteen infants not receiving any additional medication constituted the primary
      study group. Visual and quantitative analyses of aEEG/EEG and blood pressure were
      performed in 3-h epochs. RESULTS: RSI was associated with aEEG/EEG depression
      lasting <3 h. Morphine premedication resulted in aEEG/EEG depression with more
      discontinuous background and less developed cyclicity for 24 h, and during the
      first 9 h, interburst intervals (IBI) were significantly increased as compared
      with those of RSI treatment. The difference was not related to blood pressure.
      CONCLUSION: Premedication with morphine is associated with prolonged aEEG/EEG
      depression independent of blood pressure changes and may not be optimal for short
      procedures.

PMID- 23128422
TI  - Role of thrombophilic factors in full-term infants with neonatal encephalopathy.
AB  - BACKGROUND: Neonatal encephalopathy (NE) is a serious condition, primarily seen
      following hypoxia-ischemia (HI). Two different patterns of brain injury can be
      recognized on magnetic resonance imaging (MRI): white matter/watershed (WM/WS) or
      basal ganglia/thalamus (BGT) injury. Whether these patterns of injury can be
      attributed to different associated risk factors still needs to be established.
      METHODS: In 118 infants with clinical signs of NE following perinatal HI,
      thrombophilic factors, such as factor V Leiden and prothrombin gene mutation,
      C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR)
      gene, and plasma levels of homocysteine and lipoprotein(a), were prospectively
      investigated. Antenatal and perinatal variables were studied. RESULTS: WM/WS
      injury was seen in 45 infants, BGT injury in 40, and normal neuroimaging in 33.
      Antenatal factors did not differ across these groups. The BGT pattern was
      associated with lower Apgar scores, whereas the WM/WS pattern was associated with
      hypoglycemia (<2.0 mmol/l), CT or TT 677 polymorphism in the MTHFR gene, and
      plasma homocysteine levels in the upper quartile. CONCLUSION: In infants with NE
      following perinatal HI, the WM/WS pattern of injury was associated with
      hypoglycemia, the MTHFR 677CT or TT genotype, and higher levels of plasma
      homocysteine. BGT injury showed an association with signs suggestive of acute HI.

PMID- 23128423
TI  - Rosiglitazone preserves pulmonary vascular function in lambs with increased
      pulmonary blood flow.
AB  - BACKGROUND: Pulmonary vascular function is impaired with increased pulmonary
      blood flow (PBF). We hypothesized that a peroxisome proliferator-activated
      receptor-gamma (PPAR-gamma) agonist would mitigate this effect. METHODS: An aorta
      to-pulmonary-artery shunt was placed in 11 fetal lambs. Lambs received the PPAR
      gamma agonist rosiglitazone (RG, 3 mg/kg/d, n = 6) or vehicle (n = 5) for 4 wk.
      Lung tissue from five normal 4-wk-old lambs was used for comparisons. RESULTS: At
      4 wk, pulmonary artery pressure (PAP) and vascular resistance (PVR) decreased
      with inhaled nitric oxide (NO) in RG- and vehicle-treated shunt lambs. PAP and
      PVR decreased with acetylcholine (Ach) in RG-treated, but not vehicle-treated,
      shunt lambs. In vehicle-treated shunt lambs, nicotinamide adenine dinucleotide
      phosphate (NADPH) oxidase activity, rac1, superoxide, and 3-nitrotyrosine (3-NT)
      levels were increased, and Ser1177 endothelial NO synthase (eNOS) protein was
      decreased as compared with normal lambs. In RG-treated shunt lambs, NOx, Ser1177
      eNOS protein, and eNOS activity were increased, and NADPH activity, rac1,
      superoxide levels, and 3-NT levels were decreased, as compared with vehicle
      treated shunt lambs. PPAR-gamma protein expression was lower in vehicle-treated
      shunt lambs than in normal and RG-treated shunt lambs. CONCLUSION: The PPAR-gamma
      agonist RG prevents the loss of agonist-induced endothelium-dependent pulmonary
      vascular relaxation in lambs with increased PBF, in part, due to decreased
      oxidative stress and/or increased NO production.

PMID- 23128424
TI  - GPU-based fast Monte Carlo dose calculation for proton therapy.
AB  - Accurate radiation dose calculation is essential for successful proton
      radiotherapy. Monte Carlo (MC) simulation is considered to be the most accurate
      method. However, the long computation time limits it from routine clinical
      applications. Recently, graphics processing units (GPUs) have been widely used to
      accelerate computationally intensive tasks in radiotherapy. We have developed a
      fast MC dose calculation package, gPMC, for proton dose calculation on a GPU. In
      gPMC, proton transport is modeled by the class II condensed history simulation
      scheme with a continuous slowing down approximation. Ionization, elastic and
      inelastic proton nucleus interactions are considered. Energy straggling and
      multiple scattering are modeled. Secondary electrons are not transported and
      their energies are locally deposited. After an inelastic nuclear interaction
      event, a variety of products are generated using an empirical model. Among them,
      charged nuclear fragments are terminated with energy locally deposited. Secondary
      protons are stored in a stack and transported after finishing transport of the
      primary protons, while secondary neutral particles are neglected. gPMC is
      implemented on the GPU under the CUDA platform. We have validated gPMC using the
      TOPAS/Geant4 MC code as the gold standard. For various cases including
      homogeneous and inhomogeneous phantoms as well as a patient case, good agreements
      between gPMC and TOPAS/Geant4 are observed. The gamma passing rate for the 2%/2
      mm criterion is over 98.7% in the region with dose greater than 10% maximum dose
      in all cases, excluding low-density air regions. With gPMC it takes only 6-22 s
      to simulate 10 million source protons to achieve ~1% relative statistical
      uncertainty, depending on the phantoms and energy. This is an extremely high
      efficiency compared to the computational time of tens of CPU hours for
      TOPAS/Geant4. Our fast GPU-based code can thus facilitate the routine use of MC
      dose calculation in proton therapy.

PMID- 23128425
TI  - Counter-cation modulation of hydrogen and methane storage in a sodalite-type
      porous metal-organic framework.
AB  - A MU(4)-Cl bridged anionic sodalite-type porous metal-organic framework
      (Et(2)NH(2))(3)[(Cu(4)Cl)(3)(TTCA)(8)].26DEF was synthesized, in which
      Et(2)NH(2)(+) can be exchanged by Li(+) cations. The results of gas measurements
      indicate that Et(2)NH(2)(+) and Li(+) are beneficial for methane and hydrogen
      storage, respectively.

PMID- 23128426
TI  - Sphingoid bases are taken up by Escherichia coli and Staphylococcus aureus and
      induce ultrastructural damage.
AB  - Sphingoid bases found in the outer layers of the skin exhibit antimicrobial
      activity against gram-positive and gram-negative bacteria. We investigated the
      uptake of several sphingoid bases by Escherichia coli and Staphylococcus aureus,
      and assessed subsequent ultrastructural damage. E. coli and S. aureus were
      incubated with D-sphingosine, dihydrosphingosine, or phytosphingosine at ten
      times their MIC for 0.5 and 4 h, respectively, to kill 50% of viable bacteria.
      Treated bacterial cells were immediately prepared for SEM, TEM, and analyzed for
      lipid content by QTLC. E. coli and S. aureus treated with sphingoid bases were
      distorted and their surfaces were concave and rugate. Significant differences
      were observed in the visual surface area relative to controls for both E. coli
      and S. aureus when treated with dihydrosphingosine and sphingosine (p < 0.0001)
      but not phytosphingosine. While sphingoid base-treated S. aureus exhibited
      disruption and loss of cell wall and membrane, E. coli cytoplasmic membranes
      appeared intact and the outer envelope uncompromised. Both E. coli and S. aureus
      cells contained unique internal inclusion bodies, likely associated with cell
      death. QTLC demonstrated extensive uptake of sphingoid bases by the bacteria.
      Hence, sphingoid bases induce both extracellular and intracellular damage and
      cause intracellular inclusions that may reflect lipid uptake.

PMID- 23128427
TI  - Randomized clinical trial of 3 types of physical exercise for patients with
      Parkinson disease.
AB  - OBJECTIVE: To compare the efficacy of treadmill exercises and stretching and
      resistance exercises in improving gait speed, strength, and fitness for patients
      with Parkinson disease. DESIGN: A comparative, prospective, randomized, single
      blinded clinical trial of 3 types of physical exercise. SETTING: The Parkinson's
      Disease and Movement Disorders Center at the University of Maryland and the
      Baltimore Veterans Affairs Medical Center, Geriatric Research Education and
      Clinical Center. PATIENTS: A total of 67 patients with Parkinson disease who had
      gait impairment were randomly assigned to 1 of 3 arms of the trial.
      INTERVENTIONS; (1) A higher-intensity treadmill exercise (30 minutes at 70%-80%
      of heart rate reserve), (2) a lower-intensity treadmill exercise (50 minutes at
      40%-50% of heart rate reserve), and (3) stretching and resistance exercises (2
      sets of 10 repetitions on each leg on 3 resistance machines [leg press, leg
      extension, and curl]). These exercises were performed 3 times a week for 3
      months. MAIN OUTCOME MEASURES: The primary outcome measures were gait speed (6
      minute walk), cardiovascular fitness (peak oxygen consumption per unit time [$$
      VO2], and muscle strength (1-repetition maximum strength). RESULTS: All 3 types
      of physical exercise improved distance on the 6-minute walk: lower-intensity
      treadmill exercise (12% increase; P=.001), stretching and resistance exercises
      (9% increase; P<.02), and higher-intensity treadmill exercise (6% increase;
      P=.07), with no between-group differences. Both treadmill exercises improved peak
      $$ VO2 (7%-8% increase; P<.05) more than did the stretching and resistance
      exercises. Only stretching and resistance improved muscle strength (16% increase;
      P<.001). CONCLUSIONS: The effects of exercise were seen across all 3 exercise
      groups. The lower-intensity treadmill exercise resulted in the greatest
      improvement in gait speed. Both the higher- and lower-intensity treadmill
      exercises improved cardiovascular fitness. Only the stretching and resistance
      exercises improved muscle strength. Therefore, exercise can improve gait speed,
      muscle strength, and fitness for patients with Parkinson disease. The combination
      of treadmill and resistance exercises may result in greater benefit and requires
      further investigation.

PMID- 23128428
TI  - Quantitative locomotion study of freely swimming micro-organisms using laser
      diffraction.
AB  - Soil and aquatic microscopic organisms live and behave in a complex three
      dimensional environment. Most studies of microscopic organism behavior, in
      contrast, have been conducted using microscope-based approaches, which limit the
      movement and behavior to a narrow, nearly two-dimensional focal field.(1) We
      present a novel analytical approach that provides real-time analysis of freely
      swimming C. elegans in a cuvette without dependence on microscope-based
      equipment. This approach consists of tracking the temporal periodicity of
      diffraction patterns generated by directing laser light through the cuvette. We
      measure oscillation frequencies for freely swimming nematodes. Analysis of the
      far-field diffraction patterns reveals clues about the waveforms of the
      nematodes. Diffraction is the process of light bending around an object. In this
      case light is diffracted by the organisms. The light waves interfere and can form
      a diffraction pattern. A far-field, or Fraunhofer, diffraction pattern is formed
      if the screen-to-object distance is much larger than the diffracting object. In
      this case, the diffraction pattern can be calculated (modeled) using a Fourier
      transform.(2) C. elegans are free-living soil-dwelling nematodes that navigate in
      three dimensions. They move both on a solid matrix like soil or agar in a
      sinusoidal locomotory pattern called crawling and in liquid in a different
      pattern called swimming.(3) The roles played by sensory information provided by
      mechanosensory, chemosensory, and thermosensory cells that govern plastic changes
      in locomotory patterns and switches in patterns are only beginning to be
      elucidated.(4) We describe an optical approach to measuring nematode locomotion
      in three dimensions that does not require a microscope and will enable us to
      begin to explore the complexities of nematode locomotion under different
      conditions.

PMID- 23128429
TI  - [Ethical notes on the practice of medicine in prison].

PMID- 23128430
TI  - [Incidence of suicide in Catalan prisons: a descriptive and comparative study].
AB  - INTRODUCTION: The prevention of suicide in prison is one of the most important
      challenges facing prison health care services in developed countries. The aim of
      this study is to analyse the incidence of suicide in Catalan prisons and
      accumulate data about a number of variables that have also been studied in other
      prison populations. MATERIALS AND METHODS: Retrospective study of suicide cases
      in prisons administrated by the Catalan Regional Government (Generalitat de
      Catalunya) between 1990 and 2005 (n=65). Comparative study of incidence with
      European countries using published data. RESULTS: The average annual incidence
      for the period is of 59/100.000, multiplying by eight the level corresponding to
      the general population. CONCLUSIONS: Entry into prison is the most important
      event trigger for suicide. Other data open the way to new research.

PMID- 23128431
TI  - [What do prison doctors think about HIV infection control in Spanish prisons?:
      Results of the study of the Spanish Society of Prison Health Working Group on
      Infectious Diseases (GEISESP)].
AB  - We present the results of the study carried out by The Spanish Society of
      Penitentiary Health Working Group on Infectious Diseases (GEISESP) on the opinion
      of prison doctors concerning the suitability of undertaking or not undertaking
      controls of HIV infection in prisons and about the difficulties, efforts, needs
      and responsibilities that this activity may involve. This study was carried out
      in 2007 using an ad hoc survey designed and sent to doctors at 73 prisons in
      Spain. 116 valid questionnaires were received. It was considered that the data
      received could be applied to the whole population with a level of trust of 95%
      and an 8% margin of error. Half the doctors referred to prescribing
      antiretroviral treatments, though only 10% admitted prescribing rescue
      combinations. It should be noted that only of half the doctors consider
      themselves to be appropriately prepared to deal with patients infected by the HIV
      virus, though half of them admit to having received specific postgraduate
      training on this subject. Generally speaking, doctors consider that the quality
      of the health care received by the HIV-infected population is quite good.

PMID- 23128432
TI  - [SciELO: A cooperative project for the dissemination of science].
AB  - The article describes the SciELO (Scientific Electronic Library Online) model for
      the electronic publication and dissemination of scientific journals, its origin
      and evolution, methodology, components, services and potential, and its
      implantation in Spain. It consists of thirteen participant countries with eight
      certified web portals, with another 5 under development and another two thematic
      ones. In February 2009 Scielo.org had 611 magazines and 195,789 articles of which
      46% were about health sciences. Spain became a project member in 1999 and
      launched the SciELO web portal in 2001, as well as 4 magazines. It currently has
      39 titles in the field of Health Sciences; one of which is the Revista Espanola
      de Sanidad Penitenciaria, which joined the project in 2007 and which currently
      has 6 issues from 2007 and 2008 available. This makes it one of the most
      important open access initiatives existing. The report concludes by stating that
      the SciELO model contributes to the development of research and science by
      offering an effective and efficient method of promoting and increasing the
      dissemination of scientific publications in Latin America.

PMID- 23128433
TI  - [Some brief commentaries about enforced medical care for prison inmates].
AB  - A decision by the National Court in October 2005 declared that the Ministry of
      the Interior (General Directorate of Prisons) held pecuniary liability as a
      result of a concurrence of guilt between a deceased prison inmate and the prison
      Administration. It was observed that the prison health care staff had acted
      correctly when checking, diagnosing and monitoring the illness of the patient
      before and during admission. However, when faced with repeated refusals by the
      inmate to accept the prescribed treatment, they had to take suitable regulatory
      measures to comply with the terms of the indicated treatment with authorisation
      from the prison director. The Administration has a clearly established and
      undeniable liability to care for the life, integrity and health of prison inmates
      when a direct and immediate risk is observed, using force if necessary to deal
      with prolonged pathological conditions. This may bring about restrictions of the
      inmate's rights beyond those considered to be strictly necessary and lead to
      him/her being subject to the use of enforcement measures that are conceived of
      and designed for purely exceptional circumstances.

PMID- 23128434
TI  - [Escabiosis].

PMID- 23128435
TI  - MicroRNA-125b expression in gastric adenocarcinoma and its effect on the
      proliferation of gastric cancer cells.
AB  - MicroRNAs exert regulatory effects on a number of genes, thereby contributing to
      both physiological and pathological processes. The functions of microRNAs in
      tumorigenesis are becoming increasingly clear. In the present study, we
      investigated the role of microRNA-125b (miR-125b), previously implicated in
      prostate and breast cancer, in gastric cancer, particularly regarding
      proliferation and apoptosis of gastric cancer cells. The expression of miR-125b
      was measured in 50 samples of gastric cancer tissues and corresponding para
      cancerous tissues by real-time PCR. The levels of miR-125b expression in the
      gastric cancer tissues were significantly higher compared to the adjacent normal
      tissues (P<0.05). To begin to understand how the increased expression of miR-125b
      may promote gastric cancer, the miR-125b mimic was transfected into the gastric
      cancer cell line, HGC-27, for the determination of proliferation (CCK8) and
      apoptosis (Annexin V) by flow cytometry. The results demonstrated that the
      proliferation significantly increased and apoptosis significantly decreased in
      the HGC-27 cells following transfection with the miR-125b mimic, compared to the
      untreated and scramble-treated controls (P<0.05). Thus, miR-125b may act as an
      oncogene in gastric cancer by dysregulating gastric cell proliferation and
      apoptosis.

PMID- 23128436
TI  - Quality of care and analysis of surgical complications.
AB  - BACKGROUND: During the past years evaluation of quality of care has become an
      important aspect of transparency of care, and complications is one of these
      parameters. Therefore, we analyzed the complication rate in an academic hospital
      over a 6-year period. METHODS: During the period 2004-2009, all adult surgical
      patients admitted to and discharged from the Department of Surgery were selected
      for this time trend study. The Dutch national surgical complication registry was
      used in the analysis, which registers according to a three-tiered matrix-like
      classification system. Yearly changes in complication rates were analyzed
      statistically using the chi(2) for trend test. Subsequently, multivariable
      regression analysis was used to find significant independent predictors for
      sustaining a complication. RESULTS: The mean complication rate per admission rose
      significantly from 0.18 in 2004 to 0.30 in 2009 (p < 0.001). The largest increase
      was observed by the following variables: less severe complications, complex
      surgical procedures, and ASA classification. Delirium, gastoparesis, and ileus
      were complications showing the largest increase. Age, male gender, ASA, and
      surgical complexity were found as independent predictors. CONCLUSIONS: This study
      showed a significant increase of complications. The increase was mainly due to
      less severe complications, in particular delirium, ileus, and gastroparesis.

PMID- 23128437
TI  - Identification of a mimotope for circulating anti-cytokeratin 8/18 antibody and
      its usage for the diagnosis of breast cancer.
AB  - A novel circulating tumor-associated autoantibody, K94, obtained from a
      hepatocellular carcinoma (HCC) mouse model was characterized. The target antigen
      of K94 autoantibody was expressed in various tumor cell lines including liver
      cancer, and its secretion was detectable using MCF-7 breast carcinoma cells.
      Proteomic analysis revealed that the protein bands reactive to K94 included
      cytokeratin (CK) 8 and 18, which are known to be related to tumorigenesis and
      form a heterotypic complex with each other. However, K94 showed no activity
      toward CK8 or CK18 separately. The epitope of the K94 antibody was only presented
      by a complex between CK8 and CK18, which was confirmed by analysis using
      recombinant CK8 and CK18 proteins. To formulate an assay for anti-CK8/18 complex
      autoantibody, a mimotope peptide reactive to K94 was selected from loop
      constrained heptapeptide (-CX7C-) display phage library, of which sequence was
      CISPDAHSC (K94p1). A mimotope enzyme-linked immunosorbent assay (ELISA) using
      phage-displayed K94p1 peptide as a coating antigen was able to discriminate
      breast cancer (n=30) patients from normal subjects (n=30) with a sensitivity of
      50% and a specificity of 82.61%. CA15.3 was detected at very low levels in the
      same breast cancer subjects and did not discriminate breast cancer patients from
      normal subjects, although it is a conventional biomarker of breast cancer. These
      results suggest that a mimotope ELISA composed of K94p1 peptide may be useful for
      the diagnosis of breast cancer.

PMID- 23128438
TI  - Follicle-stimulating hormone and the pituitary-testicular-prostate axis at the
      time of initial diagnosis of prostate cancer and subsequent cluster selection of
      the patient population undergoing standard radical prostatectomy.
AB  - AIM: A preceding exploratory analysis has shown that follicle-stimulating hormone
      (FSH) was significantly correlated to and predicted by prostate-specific antigen
      (PSA) in a prostate cancer population. The aim of the study was to evaluate FSH
      physiopathology along the pituitary-testicular-prostate (PTP) axis at the time of
      initial diagnosis of prostate cancer in an operated population clustered
      according to the FSH/PSA ratio. PATIENTS AND METHODS: The study included 93
      patients who underwent standard radical prostatectomy. Age, percentages of
      positive cores at transrectal ultrasound scan biopsy (TRUSB) (P+), biopsy Gleason
      score (bGS), pathology Gleason score (pGS), luteinizing hormone (LH), FSH,
      prolactin hormone (PRL), total testosterone (TT), free testosterone (FT),
      estradiol (ESR) and PSA were the continuous variables. Category variables were pT
      and biopsy/pathology Gleason pattern I/II (b/pGPI/II). The population was
      clustered according to the FSH/PSA ratio which was computed from empirical data
      and then ranked for clustering the population as groups A (range 0.13 <= FSH/PSA
      <= 0.20), B (range 0.20 < FSH/PSA <= 0.50), C (range 0.50 < FSH/PSA <= 0.75), D
      (range 0.75 < FSH/PSA <= 1.00), E (range 1.00 < FSH/PSA <= 1.25), F (range 1.25 <
      FSH/PSA <= 2.00), G (range 2.00 < FSH/PSA <= 2.25), H (range 2.25 < FSH/PSA <=
      6.40) and I (range 6.40 < FSH/ PSA <= 19.40). The model was assessed by simple
      linear regression analysis and differences between the groups were investigated
      by analysis of variance (ANOVA) for continuous variables and by contingency
      tables for category variables. RESULTS: FSH was significantly correlated to and
      predicted by PSA in groups A (p = 0.04), B (p < 0.0001), C (p < 0.0001), D (p <
      0.0001), E (p < 0.0001), F (p < 0.0001), G (p < 0.0001), H (p = 0.0001) and I (p
      = 0.001). Also, clusters (A-I) differed significantly for mean values of FSH (p <
      0.0001), LH (p < 0.0001), TT (p = 0.04), PSA (p < 0.0001), bGS (p = 0.005), pGS
      (p = 0.01) and PSA/FT ratio (p < 0.0001); moreover, the nine groups showed
      significant different frequency distributions of pGPI (p = 0.02), pGPII (p =
      0.0002) and bGPI (p = 0.04). CONCLUSION: The ranking FSH/PSA ratio significantly
      clustered, along the PTP axis, an operated population diagnosed with prostate
      cancer. Also, the ranking FSH/PSA ratio selected prostate cancer clusters
      expressing different levels of hormonal disorder along the PTP axis and
      prognostic potential with different risks of progression. As a theory, in the
      current advancing world, the ranking FSH/PSA model might be considered as an
      interesting and effective tool for prostate cancer study as well as
      individualized, risk-adapted approaches of the disease. However, confirmatory
      studies are needed.

PMID- 23128439
TI  - Levetiracetam versus carbamazepine in patients with late poststroke seizures: a
      multicenter prospective randomized open-label study (EpIC Project).
AB  - BACKGROUND: Strokes are the leading cause of epileptic seizures in adults and
      account for 50% of seizures in those over the age of 65 years. The use of
      antiepileptic drugs to prevent recurrent poststroke seizures is recommended.
      METHODS: One hundred and twenty-eight patients with poststroke seizures were
      randomly allocated to treatment with either levetiracetam (LEV) or sustained
      release carbamazepine (CBZ) in a multicenter randomized open-label study. After a
      titration study phase (2 weeks), the optimal individual dose of trial medication
      was determined and treatment was continued for another 52 weeks. The primary
      endpoint was defined as the proportion of seizure-free patients; the secondary
      endpoints were: evaluation of time recurrence to the first seizure, EEG tracings,
      cognitive functions and side effects. RESULTS: Of 128 patients, 22 discontinued
      the trial prematurely; thus a total of 106 patients (52 treated with LEV and 54
      treated with CBZ) were included in the analysis. The results of the study were as
      follows: no significant difference in number of seizure-free patients between LEV
      and CBZ (p = 0.08); time to the first recurrence tended to be longer among
      patients on LEV; there was no correlation between the therapeutic effect and the
      EEG findings in either treatment group; LEV caused significantly fewer (p = 0.02)
      side effects than CBZ; attention deficit, frontal executive functions and
      functional scales (Activities of Daily Living and Instrumental Activities of
      Daily Living indices) were significantly worse in the CBZ group. CONCLUSIONS:
      This trial suggests that LEV may be a valid alternative to CBZ in poststroke
      seizures, particularly in terms of efficacy and safety. In addition, our results
      show that LEV has significant advantages over CBZ on cognitive functions. This
      trial also indicates that LEV in monotherapy is a safe and effective therapeutic
      option in elderly patients who have suffered epileptic seizures following a
      stroke.

PMID- 23128440
TI  - Proteinuria as a risk marker for the progression of chronic kidney disease in
      patients on predialysis care and the role of angiotensin-converting enzyme
      inhibitor/angiotensin II receptor blocker treatment.
AB  - BACKGROUND/AIMS: Proteinuria is a risk marker for progression of chronic kidney
      disease (CKD) and treatment with an angiotensin-converting enzyme
      inhibitor/angiotensin II receptor blocker (ACEi/ARB) is beneficial in these
      patients. However, little is known about proteinuria and ACEi/ARB treatment in
      patients on specialized predialysis care. Therefore, we investigated the
      association of urinary protein excretion (UPE) and ACEi/ARB treatment with renal
      function decline (RFD) and/or the start of renal replacement therapy (RRT) in
      patients on predialysis care. METHODS: In the PREPARE-1 cohort, 547 incident
      predialysis patients (CKD stages IV-V), referred as part of the usual care to
      outpatient clinics of eight Dutch hospitals, were included (1999-2001) and
      followed until the start of RRT, mortality, or January 1, 2008. The main outcomes
      were rate of RFD, estimated as the slope of available eGFR measurements, and the
      start of RRT. RESULTS: Patients with mild proteinuria (>0.3 to <=1.0 g/24 h) had
      an adjusted additional RFD of 0.35 ml/min/1.73 m(2)/month (95% CI: 0.01; 0.68)
      and a higher rate of starting RRT [adjusted HR: 1.70 (1.05; 2.77)] compared with
      patients without proteinuria (<=0.3 g/24 h). With every consecutive UPE category
      (>1.0 to <=3.0, >3.0 to <=6.0, and >6.0 g/24 h), RFD accelerated and the start of
      RRT was earlier. Furthermore, patients starting (n = 16) or continuing (n = 133)
      treatment with ACEi/ARBs during predialysis care had a lower rate of starting RRT
      compared with patients not using treatment [n = 152, adjusted HR: 0.56 (0.29;
      1.08) and 0.90 (0.68; 1.20), respectively]. CONCLUSION: In patients on
      predialysis care, we confirmed that proteinuria is a risk marker for the
      progression of CKD. Furthermore, no evidence was present that the use of
      ACEi/ARBs is deleterious.

PMID- 23128442
TI  - A young man with symptomatic epilepsy and right hemianopia: family affair.

PMID- 23128443
TI  - Early EEG correlates of neuronal injury after brain anoxia.

PMID- 23128444
TI  - Anti-JC Virus Antibodies in a Large German Natalizumab-Treated MS Cohort.

PMID- 23128445
TI  - Child Neurology: Krabbe disease: a potentially treatable white matter disorder.

PMID- 23128446
TI  - Pearls and oy-sters: trigeminal neuropathy associated with herpes labialis.

PMID- 23128447
TI  - Teaching Neuro Images: CSF leaks and spontaneous intracranial hypotension.

PMID- 23128448
TI  - Teaching Video NeuroImages: phenytoin-induced orofacial dyskinesias.

PMID- 23128449
TI  - Knockdown of Nrf2 enhances autophagy induced by temozolomide in U251 human glioma
      cell line.
AB  - Glioblastoma multiforme (GBM) and oxidative stress are closely linked. Oxidative
      stress affects many signaling pathways and may cause the induction of autophagy.
      The NF-E2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1)
      signaling pathway is the main pathway responsible for cell defense against
      oxidative stress and Nrf2 is a critical transcription factor related with cancer
      multidrug resistance. However, the relation between Nrf2 and regulation of
      autophagy is not well understood. In this study, we used temozolomide (TMZ),
      which inhibited the viability of GBM cells mainly by inducing autophagic cell
      death and explored the role of Nrf2 downregulation on autophagy induced by TMZ in
      GBM cells. In U251-Si-Nrf2 48 h after transfection the protein levels of Nrf2
      were significantly downregulated, while the protein levels of LC3B-II increased
      by western blot analysis. Knockdown of Nrf2 also led to a significant increase of
      autophagic vacuoles and acidic vesicular organelles (AVOs), revealed by trans
      mission electron microscopy (TEM) and acridine orange (AO) staining using flow
      cytometry. Collectively, these findings demonstrate that knockdown of Nrf2 can
      enhance the basal level of autophagy in the U251 glioma cell line. Furthermore,
      after the treatment with TMZ (100 uM) for 3 days, the U251-Si-Nrf2 transfected
      cells showed less viability rate by cell counting kit-8 (CCK-8) assay and the
      levels of autophagy increased obviously through analysis of western blot and AO
      staining using flow cytometry. Taken together, our results suggest that knockdown
      of Nrf2 may enhance autophagy induced by TMZ in the U251 glioma cell line, which
      should be further evaluated for novel anticancer activity.

PMID- 23128450
TI  - Egg intake improves carotenoid status by increasing plasma HDL cholesterol in
      adults with metabolic syndrome.
AB  - Metabolic syndrome (MetS) is associated with reductions in plasma lutein and
      zeaxanthin, along with altered composition of their lipoprotein transporters
      which may affect disease risk. Egg yolk intake has been demonstrated to increase
      plasma lutein and zeaxanthin in other populations. The objective of this study
      was to investigate the effects of whole egg feeding on plasma and lipoprotein
      carotenoids in participants with MetS. Participants consumed 3 whole eggs per day
      (EGG, n = 20) or the equivalent amount of yolk-free egg substitute (SUB, n = 17),
      as part of a carbohydrate-restricted diet (CRD) for 12 weeks. Post-intervention,
      the EGG group had significant increases in plasma lutein (+21%), zeaxanthin
      (+48%), and beta-carotene (+24%), while the SUB group had increases in plasma
      beta-carotene (+55%) only. Significant enrichment of isolated HDL and LDL
      fractions in lutein (+20% HDL, +9% LDL) and zeaxanthin (+57% HDL, +46% LDL) was
      observed in the EGG group after 12 weeks. Increases in the proportion of plasma
      carotenoids carried by HDL was seen for lutein (P < 0.01), zeaxanthin (P < 0.01),
      beta-cryptoxanthin (P < 0.05), and lycopene (P < 0.05) for all participants after
      the 12 week intervention. Daily intake of 3 whole eggs, as part of a CRD,
      increased both plasma and lipoprotein lutein and zeaxanthin. Egg yolk may
      represent an important food source to improve plasma carotenoid status in a
      population at high risk for cardiovascular disease and type 2 diabetes.

PMID- 23128451
TI  - Automated improvement of radiation therapy treatment plans by optimization under
      reference dose constraints.
AB  - A method is presented that automatically improves upon previous treatment plans
      by optimization under reference dose constraints. In such an optimization, a
      previous plan is taken as reference and a new optimization is performed toward
      some goal, such as minimization of the doses to healthy structures under the
      constraint that no structure can become worse off than in the reference plan. Two
      types of constraints that enforce this are discussed: either each voxel or each
      dose-volume histogram of the improved plan must be at least as good as in the
      reference plan. These constraints ensure that the quality of the dose
      distribution cannot deteriorate, something that constraints on conventional
      physical penalty functions do not. To avoid discontinuous gradients, which may
      restrain gradient-based optimization algorithms, the positive part operators that
      constitute the optimization functions are regularized. The method was applied to
      a previously optimized plan for a C-shaped phantom and the effects of the choice
      of regularization parameter were studied. The method resulted in reduced integral
      dose and reduced doses to the organ at risk while maintaining target homogeneity.
      It could be used to improve upon treatment plans directly or as a means of
      quality control of plans.

PMID- 23128452
TI  - Stress-related activities induced by predator odor may become indistinguishable
      by hinokitiol odor.
AB  - Predator odors, such as 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), induce a
      stress-like behavior in some rodents, and there is activation of a complex mix of
      brain regions including the anterior piriform cortex (APC) and the bed nucleus of
      stria terminalis (BST). In contrast, rose odor can counteract TMT-induced
      activation of the ventrorostral part of APC and the medial part of BST. In the
      present study, two novel odors, woody (hinokitiol) and caraway [S(+)-carvone]
      odors, were evaluated to determine whether they have an antistress effect. Plasma
      adrenocorticotropic hormone levels, a marker of stress, and the number of c-Fos
      immunopositive cells were determined in APC and BST. Plasma adrenocorticotropic
      hormone levels were increased by TMT alone and in combination with S(+)-carvone;
      however, hinokitiol with or without TMT did not have an effect. The number of
      activated cells in the medial part of BST was increased by TMT alone and in
      combination with S(+)-carvone or hinokitiol. Although TMT alone activated the
      medial part of BST, a mixture of TMT and hinokitiol activated both the medial and
      the lateral part of BST. These data suggest that the selective responses to TMT
      in the medial part of BST were obscured by activation of more odor-related
      regions by hinokitiol with TMT. In addition, the ratio of medial to lateral BST
      activation may be critical in stress-related behavior. In conclusion, hinokitiol
      can alleviate TMT-induced stress; however, the underlying mechanism appears to be
      different from that of the rose odor, as found in our previous study.

PMID- 23128453
TI  - Ambulatory surgery:  is the liability risk lower?
AB  - PURPOSE OF REVIEW: To summarize the currently available data on malpractice
      claims related to ambulatory anesthesia and provide an insight into the emerging
      patterns of anesthesia liability in this practice setting. RECENT FINDINGS: At
      present, studies are mixed about how the continued growth of outpatient surgery
      will impact liability for anesthesiologists. Data derived from the ASA Closed
      Claims Project suggests that malpractice claims for major damaging events are
      less common in the outpatient settings than in inpatient settings.
      Correspondingly, the payment amounts for outpatient claims are significantly
      lower than those for inpatients. Nevertheless, nondisabling adverse events are
      common and involve respiratory, cardiac, equipment-related, and drug errors. In
      addition, the vast majority of injuries in outpatient claims was the result of
      substandard care and judged preventable by better monitoring. Although major
      incidents leading to malpractice suits are less, new liability exposure may be on
      the horizon, due to the changing landscape of ambulatory practice that permits
      care for sicker patients who require more complex surgeries. The areas of
      potential concern include postoperative discharge criteria, care for the
      obstructive sleep apnea patient, and the choice of anesthetic techniques such as
      neuraxial blocks and monitored anesthesia care. SUMMARY: With steady increase in
      outpatient surgery, anesthesiologists are confronted with new areas of liability.
      More data are needed to identify these risks and reduce exposure to malpractice
      claims.

PMID- 23128454
TI  - Decision-making and safety in anesthesiology.
AB  - PURPOSE OF REVIEW: Anesthesiologists work in a complex environment that is
      intolerant of errors. Cognitive errors, or errors in thought processes, are
      mistakes that a clinician makes despite 'knowing better'. Several new studies
      provide a better understanding of how to manage risk while making better
      decisions. RECENT FINDINGS: Heuristics, or mental shortcuts, allow physicians to
      make decisions quickly and efficiently but may be responsible for errors in
      diagnosis and treatment. Using simple 'decision-making checklists' can help
      healthcare providers to make the correct decisions by monitoring their own
      thought processes. Anesthesiologists can adopt risk assessment tools that were
      originally developed for use by pilots to determine the hazards associated with a
      particular clinical management strategy. SUMMARY: Effective decision-making and
      risk management reduce the risk of adverse events in the operating room. This
      article proposes several new decision-making and risk assessment tools for use in
      the operating room.

PMID- 23128455
TI  - Identification of learning disabilities: implications of proposed DSM-5 criteria
      for school-based assessment.
AB  - This article examines the recommended eligibility determination for learning
      disabilities (LD) in both the Individuals with Disabilities Education Improvement
      Act and the proposed changes in diagnostic criteria in the DSM-5. The focus is on
      the inclusion of the criterion of responsiveness to intervention (RTI) and the
      implications for practice of school psychologists and general and special
      education teachers. The research base on RTI for diagnostic purposes is examined,
      and considerations of changing roles for clinicians and school-based
      practitioners are discussed.

PMID- 23128456
TI  - Implications of changes for the field: ADHD.
AB  - This article provides a thorough discussion of the proposed DSM-5 changes and
      their implications for current and future approaches to assessment,
      identification, and service delivery for children and adolescents with ADHD.
      Educational and clinical implications are discussed with special attention to the
      individual impact of the changes, diagnostic prevalence rates, and associated
      societal costs. Developmental period is considered as an important factor in the
      potential impact of the DSM-5 changes. The authors conclude that the DSM-5
      proposed revisions may improve diagnostic sensitivity and specificity; yet the
      overall impact of these changes remains largely unknown as many were not
      empirically validated. The authors suggest that the cumulative impact of the set
      of changes be considered when finalizing the DSM-5 revisions.

PMID- 23128457
TI  - Associations between procalcitonin and markers of bacterial sepsis.
AB  - BACKGROUND: Bacterial sepsis with no bacterial isolates can be a difficult
      clinical conundrum, where other markers like C-reactive protein (CRP), white cell
      count (WCC), and neutrophilia are helpful to arrive at a diagnosis. Procalcitonin
      (PCT) has been shown to be a useful biomarker in bacterial sepsis. The aim of the
      study was to look at the association of PCT with bacterial cultures and compare
      this to currently used markers of bacterial sepsis. MATERIAL AND METHODS: WCC,
      neutrophil count, and CRP with PCT were compared in patients with a positive
      bacterial culture from blood/body fluid. The specificity and sensitivity of PCT
      were compared with those of CRP. RESULTS: Of the 99 paired samples obtained, 25
      cultures were positive for bacteria. There was a significant difference in CRP
      (P=0.04) and PCT (P<0.001) levels between culture-positive and culture-negative
      samples. PCT had a better sensitivity and specificity than CRP (84% and 64.9% vs.
      69.6% and 52.9%, respectively), with a combined specificity (CRP and PCT) of
      83.5%. CONCLUSIONS: PCT has a better association with bacterial sepsis and is
      superior to currently available biomarkers in the clinical setting. The rapid
      pharmacodynamics of PCT can serve as an early predictor of the diagnosis of
      bacterial sepsis while awaiting the bacterial culture results avoiding undue
      delay in the institution of antibiotics, hence, potentially improving the
      prognosis of patients with bacterial sepsis.

PMID- 23128458
TI  - Diagnostic methods, treatment modalities, and follow-up of extracranial
      arteriovenous malformations.
AB  - OBJECTIVE: Arteriovenous malformations (AVMs) are an uncommon vascular pathology
      that remains challenging to accurately diagnose and successfully treat. This
      study introduces a novel way to evaluate AVM treatment outcomes using
      transarterial lung perfusion scintigraphy (TLPS) and reports our treatment
      results. MATERIAL AND METHODS: The patients treated for extracranial AVMs were
      studied retrospectively. Diagnosis and outcomes were based on clinical data,
      ultrasonography, magnetic resonance imaging, computed tomography, angiography,
      and TLPS studies. The influence of gender; location, form, and stage of AVMs;
      first attempt at treatment; and treatment modalities was analyzed. Outcomes were
      defined as positive (cure, improvement, and remission) or negative (no remission
      and aggravation). RESULTS: Of the 324 patients with congenital vascular
      malformations, 129 (39.8%) presented with AVMs, and the data of 56 treated
      patients with AVMs were analyzed. Of the 29 patients in the endovascularly
      treated group, 15 in the surgically treated group, and 12 in the combined
      treatment group, 24 (82.8%), 14 (93.3%), and 10 patients (83.3%), respectively,
      had positive outcomes (P>0.05). All outcomes were positive in surgically treated
      patients with extratruncular limited AVMs, and these patients were more likely to
      be cured as compared with those who had other forms of AVMs (OR, 5.8; 95% CI, 1.1
      29; P=0.02). The patients with more advanced AVMs (stages III and IV) and with
      AVMs in the gluteal and pelvic region were more likely to have the worst outcomes
      than those with stage II AVMs (OR, 8.2; 95% CI, 1-72; P=0.03) and with AVMS in
      other locations (OR, 5.8; 95% CI, 1.1-29; P=0.02), respectively. Gender and age
      did not significantly influence treatment results (P>0.05). The TLPS data of 17
      patients showed AV shunting ranging from 0% to 92%, which combined with other
      results helped identify 9 patients who needed further interventions, 6 who were
      treated successfully, and 2 who had insignificant shunting. CONCLUSIONS: The best
      outcomes were achieved in surgically treated patients with localized lesions and
      less advanced AVMs. For the first time in Lithuania, a modified TLPS method has
      been introduced that enhances a hemodynamic assessment of AV shunting and
      provides with a more accurate evaluation of AVMs to better serve in planning
      future treatments.

PMID- 23128459
TI  - The prevalence of health care-associated infections and risk factors in a
      university hospital.
AB  - The aim of the study was to evaluate the prevalence of health care-associated
      infections, risk factors, and antimicrobial use. MATERIAL AND METHODS: The study
      was carried out as a point-prevalence study in acute care wards, i.e., intensive
      care, surgical, and medical wards, at Vilnius University Hospital Santariskiu
      Klinikos in April 2010. The study variables included the patient's general data,
      indwelling devices, surgery, infection and its microbiological investigation, and
      antimicrobial use. All the variables that were logically related or had a P value
      of <0.25 in the univariate analysis were included in the stepwise logistic
      regression in order to study the factors potentially associated with health care
      associated infections. RESULTS: A total of 731 patients were surveyed. The
      overall prevalence rate of health care-associated infections was 3.8%. The
      prevalence of health care-associated infections differed by hospital wards (range
      0.0%-19.2%). The lower respiratory tract (32.2%), urinary tract (28.5%), and
      surgical site infections (32.1%) were the most common health care-associated
      infections. Moreover, 89.3% of the cases of health care-associated infections
      were microbiologically investigated. Staphylococcus aureus (28.6%) and
      Escherichia coli (19.1%) were the most frequently isolated microorganisms. The
      use of one or more invasive devices was recorded in 332 patients (45.4%). Of the
      surveyed patients, 20.2% received antimicrobial agents. The most commonly
      prescribed antimicrobial agents were fluoroquinolones (21.1%), broad-spectrum
      penicillins (19.1%), and first- or second-generation cephalosporins (18.6%).
      CONCLUSIONS: The prevalence of health care-associated infections was found to be
      similar to the reported overall prevalence rate of health care-associated
      infections in acute care hospitals in Lithuania.

PMID- 23128460
TI  - Does matrix metalloproteinase-3 polymorphism play a role in age-related macular
      degeneration in patients with myocardial infarction?
AB  - OBJECTIVE: The aim of our study was to determine if the genotype of the matrix
      metalloproteinase-3 (MMP-3) gene might carry the risk of age-related macular
      degeneration (ARMD) in patients with myocardial infarction. MATERIAL AND METHODS:
      A total of 499 patients with an acute myocardial infarction or with a history of
      myocardial infarction were enrolled into the study. They were subdivided into 2
      groups: 273 patients with ARMD and 226 patients without ARMD. The control group
      comprised 560 persons from a random sample of the Lithuanian population. DNA was
      analyzed using real-time polymerase chain reaction to genotype polymorphism 5A/6A
      at a position -1171 of the MMP-3 gene promoter. RESULTS: Of the 499 patients with
      myocardial infarction, 47% had early-stage ARMD. The patients with ARMD were
      older than the patients in the group without ARMD (62.1+/-10.8 vs. 59.6+/-11.1,
      P<0.01). The analysis of MMP-3 gene polymorphism did not reveal any differences
      in the distribution of 5A/5A, 5A/6A, and 6A/6A genotypes between the ARMD group,
      non-ARMD group, and the control group (24.2%, 52.5%, and 23.3% in the ARMD group;
      28.7%, 51.9%, and 19.4% in non-ARMD group; and 25.7%, 49.3% and 25.0%, in the
      control group, respectively). CONCLUSIONS: MMP-3 gene polymorphism had no
      predominant effect on the development of ARMD in patients with myocardial
      infarction.

PMID- 23128461
TI  - Longitudinal predictors of aerobic performance in adolescent soccer players.
AB  - BACKGROUND: The importance of aerobic performance in youth soccer is well
      established. The aim of the present study was to evaluate the contributions of
      chronological age (CA), skeletal age (SA), body size, and training to the
      longitudinal development of aerobic performance in youth male soccer players aged
      10 to 18 years. MATERIAL AND METHODS: Players (n=83) were annually followed up
      during 5 years, resulting in an average of 4.4 observations per player. Decimal
      CA was calculated, and SA, stature, body weight, and aerobic performance were
      measured once per year. Fat-free mass (FFM) was estimated from age- and gender
      specific anthropometric formulas, and annual volume training was recorded. After
      testing for multicollinearity, multilevel regression modeling was used to analyze
      the longitudinal data aligned by CA and SA (Model 1 and 2, respectively) and to
      develop aerobic performance scores. RESULTS: The following equations provide
      estimations of the aerobic performance for young soccer players: y(Model 1
      [deviance from the null model =388.50; P<0.01]) =57.75+9.06*centered CA
      0.57*centered CA(2)+0.03*annual volume training and y(Model 2 [deviance from the
      null model=327.98; P<0.01])=13.03+4.04*centered SA-0.12*centered
      SA(2)+0.99*FFM+0.03*annual volume training. CONCLUSIONS: The development of
      aerobic performance in young soccer players was found to be significantly related
      to CA, biological development, and volume of training.

PMID- 23128462
TI  - Microvascular distribution in the ocular conjunctiva and digestive tract in an
      experimental setting.
AB  - Recently improved microcirculatory imaging techniques, such as orthogonal
      polarization spectral (OPS) and its technical successor sidestream dark field
      (SDF) imaging, in handheld devices have allowed a direct observation of the
      microcirculation at the bedside. Usually a cut-off of 20 um in diameter is used
      to differentiate small vessels (mainly capillaries) from large vessels (mainly
      venules) during this technique. We hypothesized that it was possible to measure
      the small vessels with a considerably smaller inner diameter. MATERIAL AND
      METHODS: Images of the sublingual, conjunctival, jejunal, and rectal mucosa
      microcirculation were obtained with SDF videomicroscopy (Microscan(r),
      Microvision Medical, Amsterdam, the Netherlands). Using the validated software,
      the length and diameter of microvessels were manually traced with a computer
      generated line. All vessels were divided into the groups according to the inner
      diameter. RESULTS: A total of 156 SDF images of the sublingual, ocular
      conjunctival, jejunal, and rectal mucosa were taken in 13 pigs. The length of
      microscopic vessels progressively increased with a decrease in the vessel
      diameter less than 8 mm in all the lodges, such as sublingual (80.6% of total
      vessel length), ocular conjunctival (76.5% of total vessel length), jejunal
      (99.8% of total vessel length), and rectal (97.8% of total vessel length), due to
      capillary network formation. There was no significant difference in the
      distribution of vessels from 0 to 10 um in diameter comparing sublingual and eye
      conjunctival as well as jejunal and rectal mucosa. CONCLUSION: In pigs, small
      diameter microscopic vessels (<10 um) dominated in all the studied lodges
      (sublingual, ocular conjunctival, jejunal, and rectal mucosa), and this is
      evidence to establish a new cut-off for capillaries in microcirculatory analysis
      of SDF imaging in experimental and clinical studies.

PMID- 23128463
TI  - Factors influencing women's preference to select a combined hormonal
      contraceptive method: a cross-sectional survey in Lithuania.
AB  - BACKGROUND AND OBJECTIVE: Effectiveness and side effects are the main concerns
      when selecting a contraceptive method. Therefore, the aim of this study was to
      identify the preference of a combined hormonal contraception method by Lithuanian
      women, the reasons for selecting one of them and rejecting other two methods, and
      the factors determining selection or rejection. MATERIAL AND METHODS: A cross
      sectional multicenter survey was performed by the Lithuanian Society of Private
      Obstetricians and Gynecologists. A total of 4134 women, aged 18-49, who visited
      their physician due to initiation or reinitiation of hormonal contraception
      completed self-administered questionnaires identifying the reasons to select one
      method and reject the two remaining ones. Descriptive and inferential statistics
      methods were used for data analysis. RESULTS: The vaginal ring was the most
      accepted contraception method (55.4%), followed by the pill (35.6%). The skin
      patch was least preferable (9%). The vaginal ring and the skin patch were mainly
      selected for the frequency of use (72.9% and 51.2%, respectively), convenience
      (48.5% and 71%, respectively), and lower probability of noncompliance (48.7% and
      63.5%, respectively). The main reason for selecting the pill was familiarity with
      the method (50.7%). The acceptance of vaginal ring increased with age and was
      higher among women with higher education. CONCLUSIONS: The most important factors
      when selecting a contraceptive method among the methods with equal effectiveness
      and similar safety profile were convenience, frequency of use, and lower
      probability of noncompliance. Age, education, and employment status were found to
      be other reasons associated with the choice of contraceptive method.

PMID- 23128464
TI  - Incidence of inflammatory bowel disease in Kaunas region, Lithuania.
AB  - OBJECTIVE: The aim of this study was to evaluate the incidence of inflammatory
      bowel disease in Kaunas and its region during a 3-year period. MATERIAL AND
      METHODS: The study was conducted during the 3-year period (2007-2009) and
      enrolled the patients from Kaunas with its region, which has a population of
      381,300 inhabitants. The data were collected from all practices in the area where
      the diagnosis of inflammatory bowel disease was made by practicing
      gastroenterologists and consulting pediatricians along with endoscopists. Only
      new cases of inflammatory bowel disease were included into analysis. The
      diagnosis of ulcerative colitis and Crohn's disease was strictly made according
      to the Copenhagen criteria. Age- and sex-standardized incidence was calculated
      for each year of the study period. RESULTS: A total of 108 new inflammatory bowel
      disease cases were diagnosed during the study period: 87 had ulcerative colitis,
      16 Crohn's disease, and 5 indeterminate colitis. The incidence of ulcerative
      colitis, Crohn's disease, and indeterminate colitis for each study year was 6.85,
      5.33, and 7.38 per 100,000; 0.95, 1.11, and 1.57 per 100,000; and 0.47, 0.21, and
      0.42 per 100,000, respectively. The average 3-year standardized incidence of
      ulcerative colitis, Crohn's disease, and indeterminate colitis was 6.52, 1.21,
      and 0.37 per 100,000, respectively. The mean patients' age at onset of ulcerative
      colitis, indeterminate colitis, and Crohn's disease was 49.95 (SD, 17.03), 49.80
      (SD, 17.71), and 34.94 years (SD, 0.37), respectively. CONCLUSIONS: The average 3
      year incidence of ulcerative colitis in Kaunas region was found to be lower as
      compared with that in many parts of Central and Western Europe. The incidence of
      Crohn's disease was low and very similar to other countries of Eastern Europe.
      Age at onset of the diseases appeared to be older than that reported in the
      Western industrialized countries.

PMID- 23128465
TI  - Fiber-optic implantation for chronic optogenetic stimulation of brain tissue.
AB  - Elucidating patterns of neuronal connectivity has been a challenge for both
      clinical and basic neuroscience. Electrophysiology has been the gold standard for
      analyzing patterns of synaptic connectivity, but paired electrophysiological
      recordings can be both cumbersome and experimentally limiting. The development of
      optogenetics has introduced an elegant method to stimulate neurons and circuits,
      both in vitro(1) and in vivo(2,3). By exploiting cell-type specific promoter
      activity to drive opsin expression in discrete neuronal populations, one can
      precisely stimulate genetically defined neuronal subtypes in distinct circuits(4
      6). Well described methods to stimulate neurons, including electrical stimulation
      and/or pharmacological manipulations, are often cell-type indiscriminate,
      invasive, and can damage surrounding tissues. These limitations could alter
      normal synaptic function and/or circuit behavior. In addition, due to the nature
      of the manipulation, the current methods are often acute and terminal.
      Optogenetics affords the ability to stimulate neurons in a relatively innocuous
      manner, and in genetically targeted neurons. The majority of studies involving in
      vivo optogenetics currently use a optical fiber guided through an implanted
      cannula(6,7); however, limitations of this method include damaged brain tissue
      with repeated insertion of an optical fiber, and potential breakage of the fiber
      inside the cannula. Given the burgeoning field of optogenetics, a more reliable
      method of chronic stimulation is necessary to facilitate long-term studies with
      minimal collateral tissue damage. Here we provide our modified protocol as a
      video article to complement the method effectively and elegantly described in
      Sparta et al.(8) for the fabrication of a fiber optic implant and its permanent
      fixation onto the cranium of anesthetized mice, as well as the assembly of the
      fiber optic coupler connecting the implant to a light source. The implant,
      connected with optical fibers to a solid-state laser, allows for an efficient
      method to chronically photostimulate functional neuronal circuitry with less
      tissue damage(9) using small, detachable, tethers. Permanent fixation of the
      fiber optic implants provides consistent, long-term in vivo optogenetic studies
      of neuronal circuits in awake, behaving mice(10) with minimal tissue damage.

PMID- 23128466
TI  - Central pancreatectomy versus spleen-preserving distal pancreatectomy: a
      comparative analysis of early and late postoperative outcomes.
AB  - BACKGROUND/AIM: The aim of the present study is to compare the postoperative and
      long-term outcomes of central pancreatectomy (CP) and spleen-preserving distal
      pancreatectomy (SPDP). METHODS: Clinical, pathological and long-term data were
      compared between 22 patients who underwent CP and 25 patients who underwent SPDP
      (2002-2012). RESULTS: The median length of resected pancreas was 8.5 cm in the
      SPDP group and 5 cm in the CP group (p < 0.001). The median estimated blood loss
      was significantly lower in the CP group (p = 0.019). Morbidity was 50% for CPs
      and 40% for SPDPs (p = 0.564). The rate of pancreatic fistulae was 36% for CPs
      and 40% for SPDPs (p = 0.530). The rate of new-onset diabetes was nil in the
      successful CP group and 16% in the SPDP group (p = 0.111). CONCLUSION: Morbidity
      and pancreatic fistula rates are not higher after CP when compared to SPDP. The
      loss of normal pancreatic tissue is significantly lower for CP, and thus there is
      potentially better preservation of the pancreatic endocrine functions. CP should
      be considered only in selected cases when preservation of the pancreas is of
      utmost importance, especially for lesions situated at the level of the pancreatic
      neck.

PMID- 23128467
TI  - N-acetylcysteine potentiates doxorubicin-induced ATM and p53 activation in
      ovarian cancer cells.
AB  - Doxorubicin has been used clinically to treat various types of cancer, and yet
      the molecular mode of actions of doxorubicin remains to be fully unraveled. In
      this study, we investigated the effect of doxorubicin on cultured ovarian cancer
      cells (CaOV3). MTT assay data showed that doxorubicin inhibits cell proliferation
      in a time- and dose-dependent manner. Phagokinetic cell motility assay data
      indicated that doxorubicin inhibits both basal level and EGF-induced cell
      migration in CaOV3 cells. Confocal microscopic data revealed that doxorubicin
      induces reorganization of cytoskeletal proteins including actin, tubulin and
      vimentin. Doxorubicin induces phosphorylation of p53 at Ser15 and 20, acetylation
      of p53 and ATM activation. Doxorubicin also induces phosphorylation of histone
      H2AX at Ser139. Interestingly, doxorubicin also inhibits mTOR activity, measured
      by phosphorylation of S6 ribosomal protein. Pretreatment of CaOV3 cells with
      antioxidant N-acetylcysteine (NAC), but not pyrrolidine dithiocarbamate (PDTC)
      potentiates doxorubicin-induced phosphorylation of p53 and ATM. Collectively, we
      conclude that doxorubicin induces ATM/p53 activation leading to reorganization of
      cytoskeletal networks, inhibition of mTOR activity, and inhibition of cell
      proliferation and migration. Our data also suggest that removal of oxidants by
      antioxidants such as NAC may enhance the efficacy of doxorubicin in vivo.

PMID- 23128468
TI  - Gastric motility in ghrelin receptor knockout mice.
AB  - The aim of this study was to investigate the effects and possible mechanisms of
      ghrelin receptor (GHS-R) deficiency on gastric motility in GHS-R deficient (Ghsr
      /-) mice. Ghsr-/- and control (Ghsr+/+) mice were genotyped by PCR. The
      percentage of gastric emptying (GE%) was calculated following the intraperitoneal
      adminis-tration of ghrelin. In vitro, the contractile response of smooth muscle
      strips to ghrelin and electrical field stimulation (EFS) and the intraluminal
      pressure change of isolated stomach to carbachol were observed in an organ bath.
      The staining of nerve cells in the gastric muscle layer was performed by
      immunofluorescence. Delayed gastric emptying was observed in the Ghsr-/- mice;
      ghrelin enhanced the GE% in the Ghsr+/+ mice but had no effect on the GE% in the
      Ghsr-/- mice. In vitro, the response of the strips to ghrelin and EFS and the
      intraluminal pressure change to cabarchol was reduced in the Ghsr-/- mice. GHS-Rs
      were predominantly expressed on nerve cells in gastric muscle layers. The number
      of nerve cells was observed to be decreased in the Ghsr-/- mice. The delayed
      gastric emptying may relate to the loss of GHS-Rs and the reduction in the number
      of nerve cells in the gastric muscle layers of the GHS-R-deficient mice. 

PMID- 23128469
TI  - Response to vitamin D3 supplementation in obese and non-obese Caucasian
      adolescents.
AB  - BACKGROUND/AIMS: Vitamin D deficiency is highly prevalent in obese children, and
      obese children tend to respond poorly to vitamin D supplementation. The objective
      of the study was to compare the response to vitamin D(3) supplementation (2,000
      IU once daily for 12 weeks) between obese and non-obese Caucasian adolescents.
      METHODS: The study design was open label non-randomized. It was carried out at a
      single center. Eighteen obese adolescents (aged 12-18 years) and the same number
      of age-, gender- and season-matched non-obese adolescents received vitamin D(3)
      (2,000 IU/day) orally for 12 weeks. Total serum 25-hydroxyvitamin D [25(OH)D],
      parathyroid hormone, calcium and phosphorus were measured at baseline and at the
      end of the 12-week period. RESULTS: The mean baseline 25(OH)D level was higher in
      the non-obese compared to the obese subjects (mean 28.9 vs. 25.2 ng/ml; p =
      0.029). The increment in 25(OH)D levels following vitamin D supplementation was
      significantly lower in the obese adolescents (mean change 5.8 vs. 9.8 ng/ml; p =
      0.019). CONCLUSIONS: Higher doses of vitamin D are required to treat vitamin D
      deficiency in obese adolescents compared to their non-obese peers.

PMID- 23128471
TI  - [The progress of nursing towards personal fulfilment].

PMID- 23128472
TI  - [Directly observed anti-retroviral therapy amongst female inmates].
AB  - OBJECTIVES: It is considered that the gold standard for success in HAART is
      adherence. To improve adherence amongst inmates with HIV-AIDS, the use of
      directly observed treatment (DOT) is proposed using the tuberculosis treatment
      model. MATERIAL AND METHODS: HIV positive female patients with ARVT criteria who
      voluntarily participated were used for the study. The initial and final CD4 cell
      count and HIV viral load were the principal data used for assessment purposes.
      RESULTS: 52 women with an average age of 34 years were studied, with an average
      HIV infection time span of between 1 and 20 years. Initial CD4 cell count of <100
      copies/mL in 16 patients (30.7%) and an equivalent final count in 4 patients
      (7.6%) were found. Initial undetectable viral loads were not found in any
      patient, while final undetectable viral loads were found in 33 (63.4%). 21% of
      patients had opportunistic infections. The most important of these was
      tuberculosis, followed by HCV co-infection. The most frequently used ARVT
      schedule was two NRTI with one NNTRI. CONCLUSIONS: The application of DOT
      strategy to ARVT was effective amongst our patients, as shown by the increase in
      CD4 counts and the increased number of patients with reductions in viral loads to
      undetectable levels. While it is a tool that is not easy to use for cases of
      chronic treatment, we do consider it to be useful for prison inmates.

PMID- 23128470
TI  - Mannheim carotid intima-media thickness and plaque consensus (2004-2006-2011). An
      update on behalf of the advisory board of the 3rd, 4th and 5th watching the risk
      symposia, at the 13th, 15th and 20th European Stroke Conferences, Mannheim,
      Germany, 2004, Brussels, Belgium, 2006, and Hamburg, Germany, 2011.
AB  - Intima-media thickness (IMT) provides a surrogate end point of cardiovascular
      outcomes in clinical trials evaluating the efficacy of cardiovascular risk factor
      modification. Carotid artery plaque further adds to the cardiovascular risk
      assessment. It is defined as a focal structure that encroaches into the arterial
      lumen of at least 0.5 mm or 50% of the surrounding IMT value or demonstrates a
      thickness >1.5 mm as measured from the media-adventitia interface to the intima
      lumen interface. The scientific basis for use of IMT in clinical trials and
      practice includes ultrasound physics, technical and disease-related principles as
      well as best practice on the performance, interpretation and documentation of
      study results. Comparison of IMT results obtained from epidemiological and
      interventional studies around the world relies on harmonization on approaches to
      carotid image acquisition and analysis. This updated consensus document
      delineates further criteria to distinguish early atherosclerotic plaque formation
      from thickening of IMT. Standardized methods will foster homogenous data
      collection and analysis, improve the power of randomized clinical trials
      incorporating IMT and plaque measurements and facilitate the merging of large
      databases for meta-analyses. IMT results are applied to individual patients as an
      integrated assessment of cardiovascular risk factors. However, this document
      recommends against serial monitoring in individual patients.

PMID- 23128473
TI  - [Health education in prisons: assessment of an experience with diabetics].
AB  - BACKGROUND: A training strategy designed at Huelva Prison sets out to provide
      diabetic inmates with training and basic information about the illness. METHOD:
      Descriptive and cross-sectional study carried out at Huelva Prison. Information
      was acquired using questionnaires prepared for the study. A descriptive analysis
      was then made using averages for quantitative variables and absolute and relative
      frequencies for the quantitative variables. RESULTS: 27 interviewed diabetics (24
      men and 3 women), participation rate, 69.2 %, response rate 84.4%, average age
      48.3 CI 95% (43.7 to 52.9). 66.7% insulin dependent and 33.3% receiving oral anti
      diabetic treatment. Hit rate in questions assessing knowledge was over 80%.
      CONCLUSIONS: The study derives from the need to increase awareness of inmates'
      difficulties in adapting standard diets to the nutritional requirements imposed
      by the illness. Short term results such as these cannot be used to assess changes
      of attitude, although one notable conclusion that can be drawn is the high level
      of participation and interest by inmates and the consequent possibility of
      setting up self-help groups.

PMID- 23128474
TI  - [Job satisfaction of nursing staff in Spanish prisons].
AB  - BACKGROUND: There are no available studies assessing job satisfaction amongst
      nursing staff in Spanish prisons. The aim of this study is to establish overall
      levels of job satisfaction and determine each of the components. METHOD: Cross
      sectional and multi-centre descriptive study conducted in Spanish prisons. A Font
      Roja satisfaction questionnaire adapted by J. Arranz for the study was used to
      measure degrees of job satisfaction using a Likert's scale. A parametric test was
      used and a regression model was constructed for predictive ends. RESULTS: 376
      nurses answered the questionnaire (Participation Rate 62.7%; Response Rate 76.7%)
      67 centres took part (91.8%). The average satisfaction mark was 2.84 (CL 95%:
      2.81-2.87). The lowest ranked components were job variety 1.66 (CL 95%: 1.58
      1.74), job-related stress 2.15 (CL 95%: 2.08-2.23) and control over job 2.77 (CL
      95%: 2.73-2.82). The highest ranked aspect was job satisfaction, averaging 3.52
      (CL 95%: 3.44-3.58). CONCLUSIONS: The average satisfaction mark for prison
      nursing staff was low when compared to other groups of health care professionals,
      which implies the need for corrective measures.

PMID- 23128475
TI  - [Guidelines for Better Management of hepatitis B in Spain].

PMID- 23128476
TI  - [Clinical case].

PMID- 23128477
TI  - Collapsing focal segmental glomerulosclerosis in a young child.

PMID- 23128478
TI  - CD9 expression as a favorable prognostic marker for patients with malignant
      mesothelioma.
AB  - CD9 is involved in cell growth, adhesion and motility and its expression is
      reported to be of prognostic significance in various types of human malignancies.
      We found increased cell migration in the mesothelioma cell lines MSTO-211H and
      TUM1 following in vitro shRNA-mediated knockdown of CD9 expression. We
      investigated CD9 expression in 112 malignant pleural mesotheliomas. CD9
      expression was observed in 62 of 71 epithelioid, 13 of 20 biphasic and only 1 of
      21 sarcomatoid mesotheliomas. Among the epithelioid mesotheliomas (EMs), CD9
      expression was observed in all of the 33 cases with a differentiated type (EM-D)
      and in 29 of the 38 cases with a less-differentiated type (EM-LD). Patients with
      CD9 expression showed higher 1- and 2-year survival rates (63 and 25%) compared
      to the patients without CD9 expression (39 and 11%). Univariate analysis revealed
      that patients with CD9 expression demonstrated a more favorable survival
      (P=0.0025) along with other clinicopathological factors, including age younger
      than 60 years, IMIG stage I-II, epithelioid histology, EM-D and patients who
      underwent extrapleural pneumonectomy or received chemotherapy. Multivariate
      analysis identified CD9 expression as an independent prognostic factor with a
      hazard ratio (HR) of 1.99 in the analysis of all mesotheliomas (P=0.0261) and an
      HR of 2.60 in the analysis of EMs (P=0.0376). CD9 expression is an independent
      favorable prognostic marker of malignant mesothelioma.

PMID- 23128479
TI  - Magneto-capillary valve for integrated purification and enrichment of nucleic
      acids and proteins.
AB  - We describe the magneto-capillary valve (MCV) technology, a flexible approach for
      integrated biological sample preparation within the concept of stationary
      microfluidics. Rather than moving liquids in a microfluidic device, discrete
      units of liquid are present at fixed positions in the device and magnetic
      particles are actuated between the fluids. The MCV concept is characterized by
      the use of two planar surfaces at a capillary mutual distance, with specific
      features to confine the fluids by capillary forces, and the use of a gas or a
      phase-change material separating the stationary aqueous liquids. We have studied
      the physics of magneto-capillary valving by quantifying the magnetic force as a
      function of time and position, which reveals the balance of magnetic, capillary
      and frictional forces in the system. By purification experiments with a
      fluorescent tracer we have measured the amount of co-transported liquid, which is
      a key parameter for efficient purification. To demonstrate the versatility of the
      technology, several MCV device architectures were tested in a series of
      biological assays, showing the purification and enrichment of nucleic acids and
      proteins. Target recovery comparable to non-miniaturized commercial kits was
      observed for the extraction of DNA from human cells in buffer, using a device
      architecture with patterned air valves. Experiments using an enrichment module
      and patterned air valves demonstrate a 40-fold effective enrichment of DNA in
      buffer. DNA was also successfully purified from blood plasma using paraffin phase
      change valves. Finally, the enrichment of a protein biomarker (prostate-specific
      antigen) using geometrical air valves resulted in a 7-fold increase of detection
      signal. The MCV technology is versatile, offers extensive freedom for the design
      of fully integrated systems, and is expected to be manufacturable in a cost
      effective way. We conclude that the MCV technology can become an important
      enabling technology for point-of-care systems with sample in-result out
      performance.

PMID- 23128480
TI  - Yin and yang.

PMID- 23128481
TI  - Magnetic field enhanced structural instability in EuTiO3.
AB  - EuTiO(3) undergoes a structural phase transition from cubic to tetragonal at T(S)
      = 282 K which is not accompanied by any long range magnetic order. However, it is
      related to the oxygen octahedral  rotation driven by a zone boundary acoustic
      mode softening. Here, we show that this displacive second order structural phase
      transition can be shifted to higher temperatures by the application of an
      external magnetic field (DeltaT(S) ~ 4 K for MU(0)H = 9 T). This observed field
      dependence is in agreement with theoretical predictions based on a coupled spin
      anharmonic-phonon interaction model.

PMID- 23128483
TI  - [Prison Health: a view form the outside].

PMID- 23128482
TI  - Local application of drugs to study nicotinic acetylcholine receptor function in
      mouse brain slices.
AB  - Tobacco use leads to numerous health problems, including cancer, heart disease,
      emphysema, and stroke. Addiction to cigarette smoking is a prevalent
      neuropsychiatric disorder that stems from the biophysical and cellular actions of
      nicotine on nicotinic acetylcholine receptors (nAChRs) throughout the central
      nervous system. Understanding the various nAChR subtypes that exist in brain
      areas relevant to nicotine addiction is a major priority. Experiments that employ
      electrophysiology techniques such as whole-cell patch clamp or two-electrode
      voltage clamp recordings are useful for pharmacological characterization of
      nAChRs of interest. Cells expressing nAChRs, such as mammalian tissue culture
      cells or Xenopus laevis oocytes, are physically isolated and are therefore easily
      studied using the tools of modern pharmacology. Much progress has been made using
      these techniques, particularly when the target receptor was already known and
      ectopic expression was easily achieved. Often, however, it is necessary to study
      nAChRs in their native environment: in neurons within brain slices acutely
      harvested from laboratory mice or rats. For example, mice expressing
      "hypersensitive" nAChR subunits such as alpha4 L9'A mice (1) and alpha6 L9'S mice
      (2), allow for unambiguous identification of neurons based on their functional
      expression of a specific nAChR subunit. Although whole-cell patch clamp
      recordings from neurons in brain slices is routinely done by the skilled
      electrophysiologist, it is challenging to locally apply drugs such as
      acetylcholine or nicotine to the recorded cell within a brain slice. Dilution of
      drugs into the superfusate (bath application) is not rapidly reversible, and U
      tube systems are not easily adapted to work with brain slices. In this paper, we
      describe a method for rapidly applying nAChR-activating drugs to neurons recorded
      in adult mouse brain slices. Standard whole-cell recordings are made from neurons
      in slices, and a second micropipette filled with a drug of interest is maneuvered
      into position near the recorded cell. An injection of pressurized air or inert
      nitrogen into the drug-filled pipette causes a small amount of drug solution to
      be ejected from the pipette onto the recorded cell. Using this method, nAChR
      mediated currents are able to be resolved with millisecond accuracy. Drug
      application times can easily be varied, and the drug-filled pipette can be
      retracted and replaced with a new pipette, allowing for concentration-response
      curves to be created for a single neuron. Although described in the context of
      nAChR neurobiology, this technique should be useful for studying many types of
      ligand-gated ion channels or receptors in neurons from brain slices.

PMID- 23128484
TI  - [Do drug using inmates have social support?: A case study in an Andalusian
      prisons].
AB  - OBJECTIVES: To discover and compare the social support received by drug-dependent
      inmates in a drug free program and other inmates participating in a methadone
      maintenance program (MMP). MATERIALS AND METHODS: Transversal descriptive
      observational study carried out at Albolote Prison (Granada). The prison
      population at the time of the study was 1,763 inmates. The drug addicts were
      divided into two groups: those in a methadone maintenance program (MMP, 279
      inmates) and those participating in a drug free program (58 inmates). A random
      sample of 60 inmates in the MMP was obtained. All the members of the drug free
      program participated. The two groups were interviewed to discover more about
      their family structure, socio-economic level and qualifications. The MOS social
      support survey was also used in a self applied format with assistance from the
      interviewer. The percentages obtained from each dimensionof the MOS questionnaire
      for each group was compared using Pearson's chi-square test. RESULTS: The social
      network of the MMP group was a mean 13.2. In the drug free group it was 12.9.
      Value of p= 0.0047. Global support was low amongst 38 individuals (74.5%) in the
      MMP group and 9 (15.62%) in the drug free program. It was normal amongst 13
      subjects (25.5%) in the MMP group and amongst 49 (84.38%) in the drug free group.
      Value of p=0.0001. All the dimensions of the MOS social support survey are higher
      amongst the drug free group: there are statistically significant differences with
      the MMP group. CONCLUSIONS: Inmates in the drug free program have (and they
      perceive this to be the case) a greater degree of social support than
      participants in the MMP.

PMID- 23128485
TI  - [HIV infection and associated risk behaviours in a prison in Montevideo,
      Uruguay].
AB  - INTRODUCTION: The aim of this study is to establish the prevalence of HIV
      infection and associated risk behaviours amongst inmates at the Montevideo Prison
      in 2005. MATERIALS AND METHODS: The prevalence of HIV infection and different
      risk practices were analysed in a sample of 191 individuals by means of a
      serological study and personal interview based on a structured questionnaire.
      RESULTS: A prevalence of 6.5% was found for HIV infection in prison. The
      variables that proved to be risk factors were: previous prison sentences
      (p=0.009; OR= 9.51; IC95%: 1.31-144,0), having had an HIV (+) sexual partner in
      the past (p=0.000025; OR=7.87; IC95%: 2.58-23.9), current relationship with an
      HIV (+) partner (p=0.0013; OR=14.24; IC95%: 2.84-70.65), intravenous drug use
      (p=0.0001; OR=22.6; IC95%: 6.87-78.9), intravenous drug use in prison (p=0.03;
      OR=4.93; IC95%: 1.10-22.81) and sharing needles (p=0.004; OR=12.5; IC95%: 1.72
      114.7).

PMID- 23128486
TI  - [Description of the first three notified outbreaks of influenza A (H1N1) 2009 in
      Spanish prisons].
AB  - AIM: This study describes three reported outbreaks of influenza H1N1 2009 in
      Spanish prisons between july and september 2009. METHODS: An outbreak was defined
      as the appearance of three or more cases with influenza symptoms and with an
      epidemiological link in the same module of a prison. The outbreaks were reported
      using a specific questionnaire. The analysis, which used variables of gender,
      age, date of notification, duration of outbreak, risk factors and clinical
      features are presented as absolute numbers, percentages and attack rates, while
      study of the diffusion of the illness is expressed as epidemic curves. RESULTS:
      Three outbreaks were reported at the prisons of Alcala-Meco (85 affected males),
      Pamplona (18 affected males) and Jaen (12 affected females) with an overall
      attack rate that ranged from 7.1% to 17.9%. Duration of the outbreaks was between
      8 and 35 days, and the average duration of the illness itself was 3 days. Only 4
      inmates were admitted who were later given discharges for recovery. The men were
      younger (p<0.001). The epidemiological curves of the outbreaks did not show any
      clear propagation patterns. DISCUSSION: The attack rates are highly variable
      although they are lower than other community outbreaks. Symptoms were slight and
      lethality was zero. The women's age was significantly greater that that of the
      men, although it is practically the same amongst the prison population. Low
      morbidity was very probably the cause of the reduction in consultations of the
      persons affected and the consequent underestimation of the rates.

PMID- 23128487
TI  - [Conscientous health objection in the prison environment].
AB  - To be fully in accordance with constitutional doctrines the notion of
      conscientious objection must be understood as a manifestation of the fundamental
      right to ideological freedom as contained in art. 16.1 CE (assuming of course
      that all objecting conduct is legitimate), but it must also be understood as a
      principle. That is to say, any conflict between the subject's fundamental right
      and legal duty that he rejects must be resolved by the judge who must make a
      careful judgement of values and property. This fundamental right still exists and
      may invoked and exercised by inmates and health personnel in the prison context
      in the face of predictions of the forcible imposition of medical treatment as
      stated in the LOGP and RP, with no more limit than public order itself.

PMID- 23128488
TI  - Review of the success of pulp exposure treatment of cariously and traumatically
      exposed pulps in immature permanent incisors and molars.
AB  - The decision to retain immature permanent tooth with pulp disease is
      problematical. Restoring the tooth would normally involve some form of pulp
      capping/pulpotomy procedure or a more radical pulpectomy and root canal
      treatment. Pulp capping/pulpotomy procedures, where all or part of the pulp is
      retained, relies upon an accurate assessment of the pulp condition, and the
      careful management of the remaining healthy tissue. Pulpectomy or root canal
      treatment is technically difficult as the root apex is open with the result that
      conventional preparation and filling techniques are compromised. On the other
      hand, the inappropriate extraction of immature teeth with pulp disease will
      result in immediate aesthetic and functional difficulties that may require the
      patient to have orthodontic or restorative care that will have potential life
      long implications, e. g. removable or fixed prosthesis. The aim of this article
      is to provide an overview of the aetiology of pulp disease in immature teeth and
      to review current evidence of the outcome of conservative pulp treatment.

PMID- 23128489
TI  - Needs for prosthetic treatment in Vilnius population at the age over 45 years
      old.
AB  - AIM OF THE STUDY. The aims of the study was to evaluate needs for prosthetic
      treatment among middle-aged and elderly population in Vilnius, to find out rates
      of edentulism among Vilnius inhabitants and to ask them about their approach to
      personal oral hygiene. MATERIALS AND METHODS. This cross-sectional study was
      approved by Lithuanian Bioethics Committee and carried out by one investigator.
      Our study was performed in period from 2008 to 2012. We have examined and
      interviewed 634 patients in the principle of free choice (randomized selection).
      Quantity of remaining teeth and previous prosthetic treatment was assessed.
      RESULTS. According to questionnaire previous prosthetic treatment was attached
      for 204 (43.8%) male and 262 (56.8%) female patients, total 466 (73.5%) of all
      subjects involved into our research, 168 (26.5%) never had a prosthetic
      treatment. During examination we found, that 219 (34.5%) of all examined persons
      were treated with removable prosthesis, 180 (28.4%) treated with fixed prosthesis
      and for 67 (10.6%) both: fixed and removable kinds of prosthesis were attached.
      Toothless jaws were found in 26.5% (n = 168) of population. We found 179 (28.2%)
      edentulous maxillas and 168 (26.5%) mandibles. CONCLUSIONS. The intensity of
      tooth loss in the middle-aged and eldery population of Vilnius city significantly
      increases with age. Lower rates of edentulism and an ageing population mean that
      older people will feature more prominently in dental services. Consolidation in
      oral health perceptions starts before age 50, suggesting early intervention
      before that age.

PMID- 23128490
TI  - Augmentation of atrophic posterior maxilla by short implants and osteotome
      technique.
AB  - INTRODUCTION. Edentulous ridge in the posterior maxilla is often compromised by
      reduced bone volume. This anatomical condition limits the implant placement of 10
      mm in length without sinus augmentation. The use of shorter implants with
      osteotome technique minimizes the need of more extensive sinus floor elevation,
      thus reducing the duration and morbidity of the treatment. MATERIALS AND METHODS.
      A prospective study was conducted of all patients treated between Nov 2007 and
      Nov 2008 who received endosseous implants that were less than 10 mm in length.
      Patient age, gender, height bone residual of posterior maxilla, location of
      implants, number and type of implants and Albrektsson criteria for success were
      assessed. RESULTS: A total of 25 implants of 8 mm in length were placed with
      primary stability in 11 patients. Cumulative survival rates for implants were
      100%. CONCLUSION. This simplified treatment modality can make implant
      rehabilitation of the atrophic posterior maxilla more accessible.

PMID- 23128491
TI  - Immediate post-treatment crowned Herbst effects in growing patients.
AB  - OBJECTIVE. The aim of this prospective study was to describe the mechanism of
      Class II correction in growing patients induced by crown Herbst (cHerbst)
      appliance as an immediate result of therapy. MATERIALS AND METHODS. Forty
      patients (mean age 13.6 +/- 1.3 years) with stable Class I occlusion 1 year
      following treatment with the cHerbst appliance were selected from a prospective
      sample of 180 consecutively treated Class II patients. No other appliances were
      used during treatment. The immediate dentoskeletal changes after discontinuing
      cHerbst therapy were compared with a matched sample of untreated Class II
      subjects (mean age 13.9 +/- 1.6 years). Lateral cephalograms were taken before
      treatment and immediately after one year therapy. RESULTS. Treatment produced
      significant skeletal changes: increase in mandibular length and SNB angle,
      decrease of ANB angle, restricted growth of posterior maxilla. Significant
      dentoalveolar changes: maxillary molars moved backwards and tipped distally,
      lower first molars moved forward and extruded, lower incisors proclined, upper
      incisors retroclined, overjet and overbite decreased. CONCLUSIONS. Immediate
      postreatment results revealed that Class II was mainly corrected due to
      dentoalveolar changes and only limited skeletal change.

PMID- 23128492
TI  - Standards for permanent teeth emergence time and sequence in Lithuanian children,
      residents of Vilnius city.
AB  - BACKGROUND. Up-to-date population specific standards on the timing and sequence
      of emergence of the permanent teeth are essential in planning medical care for
      children. To the best of authors' knowledge, data about emergence time of
      permanent teeth in Lithuanian children has not been provided. OBJECTIVE. To
      provide the first standards of permanent teeth emergence time and sequence in
      Lithuanian children, citizens of Vilnius. MATERIAL AND METHODS. In a cross
      sectional study, data were collected from 3596 Lithuanian children, 4 to 16 years
      of age in randomly selected kindergartens and secondary schools of Vilnius city.
      During dental examination all erupted permanent teeth, except third molars, were
      recorded. MiniTab15 statistical software was used to calculate clinical eruption
      time of permanent teeth. Different comparisons were made to detect inter-jaw,
      inter-gender and inter-population differences. RESULTS. The earliest teeth to
      erupt in both genders are lower central incisors around the age of six. The first
      stage of mixed dentition ends with the eruption of upper lateral incisors around
      the age of 8 in boys and a half of year earlier in girls. Second transitional
      period starts after the emergence of first premolars or lower canine in girls and
      upper first premolar in boys at the age of 9.5. The last tooth to erupt in both
      genders is the upper second molar at the age of twelve. No significant
      differences have been found between right and left sides in either jaw. Lower
      permanent teeth tended to emerge significantly earlier than the upper ones,
      except for premolars and first molars. Girls preceded boys by 4 to 5 months on
      average. Lithuanian children on average showed earlier emergence time, especially
      in premolars, but resemble German and Finnish populations more closely.
      CONCLUSIONS. No significant asymmetry in permanent teeth emergence time has been
      found in either jaw. Lower permanent teeth, showed earlier clinical eruption than
      in the upper jaw in both genders. Lithuanian girls were clearly advanced in
      permanent teeth emergence than compared to boys. Lithuanian children showed
      earlier permanent teeth emergence time, especially in premolar region, than
      children from other countries.

PMID- 23128493
TI  - Abnormal expression of the mitotic checkpoint protein BubR1 contributes to the
      anti-microtubule drug resistance of esophageal squamous cell carcinoma cells.
AB  - Esophageal cancer is a common malignancy with a high mortality rate. The lack of
      effective chemotherapy and a means to overcome drug resistance leads to the
      predictable failure of esophageal cancer treatment. Mitotic checkpoint proteins
      play a critical role in regulating the cell cycle and proliferation. Abnormal
      expression of the mitotic checkpoint protein BubR1 has been reported in several
      types of cancers. In this study, we investigated the role of BubR1 in conferring
      resistance of esophageal cancer cells to anti-microtubule drugs. Using
      quantitative real-time PCR analysis on 50 samples of paired esophageal squamous
      cell cancer (ESC) tissues and adjacent non-cancerous tissues, we found that 72%
      (36 of 50) of the analyzed ESC samples exhibited high expression levels of BubR1,
      which was also confirmed in ESC cell lines. ESC cells with high levels of BubR1
      were less sensitive to the anti-microtubule drugs paclitaxel and nocodazole.
      Recombinant adenovirus-mediated enforced expression of BubR1 in relatively
      sensitive ESC cell lines resulted in increased resistance to paclitaxel.
      Conversely, RNAi-mediated knockdown of BubR1 restored ESC cell sensitivity to
      paclitaxel. Cell cycle analysis indicated that the sub-G1 population increased in
      the ESC cells with reduced BubR1 levels. Taken together, our results suggest that
      upregulation of BubR1 expression may be associated with ESC resistance to
      paclitaxel treatment. Thus, BubR1 may serve as a potential chemosensitizing
      target to overcome chemoresistance.

PMID- 23128494
TI  - B7-H3 expression in ductal and lobular breast cancer and its association with IL
      10.
AB  - Aberrant tumor cell expression of B7-H3, a member of the B7-family that
      stimulates interleukin-10 (IL-10) secretion, contributes to tumor immune evasion
      and tumor progression. The aim of this study was to investigate the expression of
      B7-H3 and IL-10 in ductal and lobular breast cancer tissues. Using
      immunohistochemistry, B7-H3 and IL-10 protein expression in tumor specimens of
      primary human breast cancer was investigated. The association between B7-H3 or IL
      10 expression and clinicopathological variables was analyzed. The correlation
      between the expression of B7-H3 and IL-10 was also evaluated. In tumor tissues,
      the expression of B7-H3 and IL-10 was identified on the cell membrane and in the
      cytoplasm. Expression of B7-H3 was observed in 90.60% (106/117) of the specimens
      and 80.34% (94/117) expressed IL-10. Patients with a positive B7-H3 or high IL-10
      expression were more likely to have positive lymph node metastasis (N1-3; P=0.018
      or 0.035, respectively) and advanced disease (stage II-IV; P=0.011 or 0.039,
      respectively) compared to those with a negative or low expression. Furthermore,
      B7-H3 expression was correlated with IL-10 in tumor cells (R=0.545, P=0.000).
      High B7-H3 expression in human breast cancer tissues may be important in tumor
      progression and invasiveness. This expression appeared to be correlated with the
      ability of B7-H3 to promote IL-10 secretion. 

PMID- 23128496
TI  - The importance of superior vena cava isolation in ablation strategy for atrial
      fibrillation.
AB  - PURPOSE OF REVIEW: Superior vena cava (SVC) is one of the most important
      nonpulmonary vein origins of atrial fibrillation, and SVC should be carefully
      treated in order to decrease the recurrence of atrial fibrillation after
      ablation. Despite the fact that pulmonary vein isolation (PVI) should be
      performed prophylactically for all pulmonary veins, prophylactic SVC isolation
      (SVCI) is still controversial. This review describes recent data on treatments
      for SVC focus during atrial fibrillation ablation. RECENT FINDINGS: There are two
      different major approaches to treat SVC focus during atrial fibrillation
      ablation. One is the conventional approach, in which SVCI is performed only if
      atrial fibrillation from SVC origin is recognized using pacing maneuvers and/or
      isoproterenol infusions. Another approach is performing SVCI in all cases
      prophylactically in addition to PVI. The rate of atrial fibrillation freedom 1
      year after initial atrial fibrillation ablation by prophylactic PVI along with
      SVCI was almost the same as with the conventional method (85-90% atrial
      fibrillation freedom). In addition, the conventional method also had a good
      result even 5 years after ablation (73.3%). SUMMARY: Because of the good result
      after using the conventional approach and possible complications during SVCI,
      SVCI should be performed only if SVC focus is recognized, not prophylactically.

PMID- 23128498
TI  - Unexplained sudden death, focussing on genetics and family phenotyping.
AB  - PURPOSE OF REVIEW: Unexplained sudden death and the sudden arrhythmic death
      syndrome (SADS) affect a small but significant proportion of young and apparently
      healthy individuals. This review revisits the causes underlying such deaths and
      the investigational strategies that identify surviving family who may be at risk.
      RECENT FINDINGS: Recent epidemiological data is available from case series or
      government records. The yield from familial cardiological evaluation for
      inherited conditions has been supported by additional small series. The greatest
      advance has come with molecular autopsy studies, which have utilized various
      methodologies and candidate genes to investigate SADS cases and their families.
      SUMMARY: The latest research replicates and extends the existing knowledge
      regarding epidemiology and familial evaluation of SADS, whilst genetic studies
      support a role for the molecular autopsy.

PMID- 23128497
TI  - Genetic testing in heritable cardiac arrhythmia syndromes:  differentiating
      pathogenic mutations from background genetic noise.
AB  - PURPOSE OF REVIEW: In this review, we summarize the basic principles governing
      rare variant interpretation in the heritable cardiac arrhythmia syndromes,
      focusing on recent advances that have led to disease-specific approaches to the
      interpretation of positive genetic testing results. RECENT FINDINGS: Elucidation
      of the genetic substrates underlying heritable cardiac arrhythmia syndromes has
      unearthed new arrhythmogenic mechanisms and given rise to a number of clinically
      meaningful genotype-phenotype correlations. As such, genetic testing for these
      disorders now carries important diagnostic, prognostic, and therapeutic
      implications. Recent large-scale systematic studies designed to explore the
      background genetic 'noise' rate associated with these genetic tests have provided
      important insights and enhanced how positive genetic testing results are
      interpreted for these potentially lethal, yet highly treatable, cardiovascular
      disorders. SUMMARY: Clinically available genetic tests for heritable cardiac
      arrhythmia syndromes allow the identification of potentially at-risk family
      members and contribute to the risk-stratification and selection of therapeutic
      interventions in affected individuals. The systematic evaluation of the 'signal
      to-noise' ratio associated with these genetic tests has proven critical and
      essential to assessing the probability that a given variant represents a rare
      pathogenic mutation or an equally rare, yet innocuous, genetic bystander.

PMID- 23128499
TI  - Ethical and legal perspective of implantable cardioverter defibrillator
      deactivation or implantable cardioverter defibrillator generator replacement in
      the elderly.
AB  - PURPOSE OF REVIEW: Implantable cardioverter defibrillator (ICD) implantation has
      become a common and standard treatment for primary and secondary prevention of
      sudden cardiac death in patients with poor left ventricular ejection fraction
      across the world. Circumstances, of course, change after the initial implant as
      patients age. This raises legal and ethical questions about deactivating or not
      replacing ICD generators when the likelihood of meaningful benefit has
      diminished. RECENT FINDINGS: Health professionals are reluctant to discuss the
      end-of-life planning with patients who have ICDs. Older patients are more likely
      to have multiple comorbidities that worsen or accumulate further after initial
      implantation and attenuate the survival benefit of ICDs. Joint guidelines suggest
      physicians educate patients during the initial consent process about the
      possibility of deactivating ICDs after implantation if their individual situation
      changes to the point of futility. SUMMARY: ICD deactivation and nonreplacement
      are unavoidable issues that require clarity for meaningful and ethical
      implementation. This is an ongoing process.

PMID- 23128501
TI  - New anthraquinone derivatives as inhibitors of the HIV-1 reverse transcriptase
      associated ribonuclease H function.
AB  - BACKGROUND: The degradative activity of the human immunodeficiency virus type 1
      (HIV-1) reverse transcriptase (RT), termed ribonuclease H (RNase H), which
      hydrolyzes the RNA component of the heteroduplex RNA:DNA replication
      intermediate, is an excellent target for drug discovery. Anthraquinones (AQs) and
      their derivatives, which are common secondary metabolites occurring in bacteria,
      fungi, lichens and a large number of families in higher plants, have been
      reported to have several biological activities including that of inhibiting HIV-1
      RT activities in biochemical assays. METHODS: We have assayed new AQ derivatives
      on HIV-1 RNase H activities in biochemical assays. RESULTS: Six series of new AQ
      derivatives with various substituents at positions 1, 2, 3 and 4 of the AQ ring
      were tested, and new analogs able to inhibit HIV-1 RT-associated RNase H activity
      in the low micromolar range were found. CONCLUSIONS: Our results demonstrate that
      AQ derivatives are promising anti-RNase H inhibitors.

PMID- 23128502
TI  - Highly efficient vinylaromatics generation via iron-catalyzed sp3 C-H bond
      functionalization CDC reaction: a novel approach to preparing substituted
      benzo[alpha]phenazines.
AB  - An iron-catalyzed benzylic vinylation was developed to transfer the carbon atom
      in the N,N-dimethyl moiety of N,N-dimethylacetamide (or N,N-dimethylformamide) to
      2-methyl azaarenes to generate 2-vinyl azaarenes.

PMID- 23128503
TI  - Seeking tolerance indirectly.

PMID- 23128504
TI  - Treosulfan-based conditioning in DOCK8 deficiency: complete lympho-hematopoietic
      reconstitution with minimal toxicity.

PMID- 23128505
TI  - Hydrogen shuttling: synthesis and reactivity of a 14-electron iridium complex
      featuring a bis(alkyl) tethered N-heterocyclic carbene ligand.
AB  - Solvent dependent double C-H activation in an Ir(NHC)(2) system generates an
      agostically stabilized 14-electron complex featuring a face-capping bis(alkyl)
      tethered NHC ligand [NHC = N-heterocyclic carbene]. These activation processes
      are reversible, and the resulting ligand-derived hydrogen shuttle can be applied
      to the dehydrogenation of BN-containing substrates.

PMID- 23128506
TI  - Response to editorial note on: agreement of repeated motor and sensory scores at
      individual myotomes and dermatomes in young persons with spinal cord injury.

PMID- 23128507
TI  - Signaling pathways in follicular cell-derived thyroid carcinomas (review).
AB  - Thyroid carcinoma is the most common malignant endocrine neoplasia.
      Differentiated thyroid carcinomas (DTCs) represent more than 90% of all thyroid
      carcinomas and comprise the papillary and follicular thyroid carcinoma subtypes.
      Anaplastic thyroid carcinomas correspond to less than 1% of all thyroid tumors
      and can arise de novo or by dedifferentiation of a differentiated tumor. The
      etiology of DTCs is not fully understood. Several genetic events have been
      implicated in thyroid tumorigenesis. Point mutations in the BRAF or RAS genes or
      rearranged in transformation (RET)/papillary thyroid carcinoma (PTC) gene
      rearrangements are observed in approximately 70% of papillary cancer cases.
      Follicular carcinomas commonly harbor RAS mutations and paired box gene 8 (PAX8)
      peroxisome proliferator-activated receptor gamma (PPARgamma) rearrangements.
      Anaplastic carcinomas may have a wide set of genetic alterations, that include
      gene effectors in the mitogen-activated protein kinase (MAPK),
      phosphatidylinositol 3-kinase (PI3K) and/or beta-catenin signaling pathways.
      These distinct genetic alterations constitutively activate the MAPK, PI3K and
      beta-catenin signaling pathways, which have been implicated in thyroid cancer
      development and progression. In this context, the evaluation of specific genes,
      as well as the knowledge of their effects on thyroid carcinogenesis may provide
      important information on disease presentation, prognosis and therapy, through the
      development of specific tyrosine kinase targets. In this review, we aimed to
      present an updated and comprehensive review of the recent advances in the
      understanding of the genetic basis of follicular cell-derived thyroid carcinomas,
      as well as the molecular mechanisms involved in tumor development and
      progression.

PMID- 23128509
TI  - The value of community health workers.

PMID- 23128508
TI  - Magnetically labelled gold and epoxy bi-functional microcarriers for suspension
      based bioassay technologies.
AB  - Microarrays and suspension-based assay technologies have attracted significant
      interest over the past decade with applications ranging from medical diagnostics
      to high throughput molecular biology. The throughput and sensitivity of a
      microarray will always be limited by the array density and slow reaction
      kinetics. Suspension (or bead) based technologies offer a conceptually different
      approach, improving detection by substituting a fixed plane of operation with
      many individually distinguishable microcarriers. In addition to all the features
      of a suspension based assay technology, our technology offers a rewritable label.
      This has the potential to be truly revolutionary by opening up the possibility of
      generating, on chip, extensive labelled molecular libraries. We unveil our latest
      SU-8 microcarrier design with embedded magnetic films that can be utilized for
      both magnetic and optical labelling. The novel design significantly simplifies
      fabrication and additionally incorporates a gold cap to provide a dual surface,
      bi-functional architecture. The microcarriers are fabricated using deep
      ultraviolet lithography techniques and metallic thin film growth by evaporation.
      The bi-functional properties of the microcarriers will allow us to use each
      microcarrier as its own positive control thereby increasing the reliability of
      our technology. Here we present details of the design, fabrication, magnetic
      detection and functionalization of these microcarriers.

PMID- 23128510
TI  - Gender differences in alcohol choice among Russians: evidence from a quantitative
      study.
AB  - AIMS: Qualitative studies find that men and women in Russia have different
      preferences for alcoholic beverages, but quantitative evidence for gender
      differences in beverage type choice remains scarce. The purpose of this article
      is to test numerically whether and to what extent men and women in Russia differ
      in terms of preferences for type of drink, such as vodka, wine and beer. METHODS:
      Results are based on multinomial logistic regression and ordinary least squares
      regression analyses of the Russian Longitudinal Monitoring Survey-Higher School
      of Economics 2008 data. RESULTS: We observed significant gender differences in
      preferences for alcoholic beverages. Men have strong preferences for vodka, and
      they drink it in much larger amounts in comparison with women. Women are more
      likely to either refrain from drinking or drink mild types of alcoholic
      beverages, such as wine and beer. Gender differences remain statistically
      significant even when sociodemographic factors are well accounted for.
      CONCLUSIONS: The present study confirms the previous research findings about
      gender differences in drinking practices among Russians. Our results provide
      quantitative evidence of the pronounced differences in beverage types consumed by
      men and women.

PMID- 23128511
TI  - Providing care for GLBTQ patients.

PMID- 23128512
TI  - 2nd International Congress on Neurology and Epidemiology.

PMID- 23128513
TI  - Direct cardiac ventriculoatrial shunt: technical note.
AB  - There are a number of choices for placement of the distal catheter during
      ventricular shunting for hydrocephalic patients. In very rare instances, patients
      with multiple revisions can no longer have their shunt placed in the routine
      locations. We describe the placement of the distal catheter into the atrium
      through direct cardiac access, a technique described decades ago but rarely
      needed in clinical practice. This can be a useful location in the limited number
      of patients who have exhausted other more routine locations.

PMID- 23128514
TI  - The theory of electron-phonon superconductivity: does retardation really lead to
      a small Coulomb pseudopotential?
AB  - The theory of electron-phonon superconductivity depends on retardation
      drastically  reducing the effects of the strong Coulomb repulsion. The standard
      theory only treats the lowest order diagram, which is an uncontrolled
      approximation. We study retardation in the Hubbard-Holstein model in a controlled
      way using perturbation theory and dynamical mean-field theory. We calculate
      second order results for the pseudopotential MU* analytically and demonstrate the
      validity up to intermediate couplings by comparison with non-perturbative
      results.  Retardation effects are still operative, but less efficient, leading to
      somewhat larger values of MU*. Therefore, our theory can help in the
      understanding of situations where the standard theory yields overestimates for
      T(c).

PMID- 23128515
TI  - Pharmacometrics: a quantitative tool of pharmacological research.

PMID- 23128516
TI  - Effectiveness of coadministration of varenicline, bupropion, and serotonin
      reuptake inhibitors in a smoking cessation program in the real-life setting.
AB  - INTRODUCTION: Varenicline has a significant impact on the ability to quit
      smoking. However, patients may have side effects similar to nicotine withdrawal
      symptoms. The aim of this study was to evaluate the effectiveness of varenicline
      in monotherapy or in combined therapy with bupropion and/or serotonin reuptake
      inhibitors (SRIs) in a specific cardiovascular smoking cessation service.
      METHODS: It is an outcome research of 427 patients that received varenicline
      monotherapy or combined pharmacotherapy and were followed for 52 weeks. Patients
      were oriented to take varenicline until week 12. During each medical visit, the
      patients were evaluated and in the cases of mood changes after varenicline use,
      SRIs were prescribed. Bupropion was combined in patients that did not achieve
      complete tobacco abstinence in 2 or 3 weeks after starting varenicline use or if
      the patient presented uncomfortable abstinent symptoms. RESULTS: The success
      (continuous abstinence rate in 52 weeks) in different drug regimens were:
      varenicline monotherapy (32.1%), varenicline + bupropion (55.0%), varenicline +
      SRI (50.6%), and varenicline + bupropion + SRI (57.7%). In a multivariate
      analysis of successful treatment predictors, compared with varenicline
      monotherapy, patients who used bupropion + SRI adjuvant treatment had an odds
      ratio (OR) of 5.05 (1.99-12.80) for a successful treatment response after 1-year
      follow-up, while patients who used bupropion or SRI had OR of 3.21 (1.68-6.14)
      and 3.58 (1.98-6.48), respectively. CONCLUSIONS: Our results suggest that
      adjuvant treatment to varenicline therapy may be associated with improved success
      in smoking cessation, especially in patients with nicotine withdrawal symptoms.
      These results should be tested in randomized controlled trials.

PMID- 23128517
TI  - Regulatory issues concerning the development and circulation of nicotine
      containing products: a qualitative study.
AB  - INTRODUCTION: This paper explores perceptions of how the regulation of nicotine
      containing products (NCPs) impacts the development and availability of more
      effective cigarette substitutes. METHODS: Qualitative study using semistructured
      interviews with 20 key stakeholders (7 academic experts in tobacco control, 5
      representatives of 3 pharmaceutical companies, and 8 representatives of
      organizations involved in tobacco-control policy making) and documentary
      analysis. RESULTS: Four main themes were identified. In general, currently
      available nicotine replacement therapies (NRTs) were considered to be relatively
      unsuccessful as substitutes because they deliver insufficient nicotine too
      slowly. Stronger, faster-acting nicotine products were deemed necessary. However,
      issues were raised about how smokers may perceive stronger, faster-acting
      products linked to misunderstandings about nicotine. Pharmaceutical companies
      have shown reluctance to pursue NRT development; discussions around harm
      reduction are shifting company attitudes, although concerns remain about the
      impact of developing more addictive products on company image and whether such
      products would be problematic to license. The greater cost of producing an NCP
      within the medical regulatory regime, compared with cigarettes, was underlined.
      Recreational NCPs were considered problematic as they do not currently need to
      meet the high regulatory standards required for medications. CONCLUSIONS:
      Although experts generally agreed that NRT development ought to focus on stronger
      and faster-acting products, questions were raised over whether this aligns with
      smokers' understandings and requirements. A more nuanced grasp of how smokers
      understand harm-reduction approaches and products is required. Pharmaceutical
      companies may not be best placed to innovate, indicating that the market may well
      be left to other actors including the tobacco industry.

PMID- 23128518
TI  - [Health protection's current challenge: Why every health department must consider
      The Madrid Recommendation].

PMID- 23128519
TI  - [Care for cases of somatomorphic disorders in the prison population].
AB  - This study sets out to make a worthwhile contribution to healthcare personnel
      working in the prison sector by providing theoretical and technical knowledge to
      enable them to better understand and care for people in prison who suffer from
      these disorders. As far as we know, the cognitive integration of a descriptive
      and comprehensive model, bearing in mind a theory of the observed phenomenon acts
      as an emotionally constraining factor for the anxieties we suffer in the
      therapeutic relationship with our patients. Consequently we also wish to
      contribute with this study to improving the emotional resources of personnel
      working in a context as anxiety-provoking as is a prison, while also pointing out
      the risks inherent to any theory that might be used to conceal clinical
      realities.

PMID- 23128520
TI  - [Strategic health plan for federal prisons in Argentina].
AB  - In the last five years, medical care policies for prisons in the Argentine
      Federal Penitentiary Service were developed by the previous Medical Care
      Assistance Office of this Institution to improve primary medical healthcare.
      Policies were applied with heterogeneous criteria in comparison to the ones
      established by the Ministry of Health. This may be why I am interested in taking
      a deeper look at the Argentine experience in order to guarantee human rights,
      especially access to health for inmates based in the Federal Penitentiary
      Service. These changes could only be brought about by penal reforms such as
      reductions in overpopulation, the increase of the number of workers and students
      among inmates, including socio - cultural activities, the creation of
      penitentiary treatment programmes for first time inmates, adults, and mental
      disabilities programmes for inmates with a background of drug abuse, which have
      represented a great step forward towards the fulfilment of the duties of the
      state. This novel, integrated approach to medical care policies for imprisoned
      people is based on the assumed responsibility of the Ministry of Justice together
      with the Health Ministry, enabling equal access to community health assistance in
      a closed environment like prison. The reform of medical care policies in federal
      prisons, leads us to us reflect on the revolutionary changes in public policy
      management that had not been presented up till now, and that now show a change in
      direction that the Argentine State has taken towards effective guarantees of
      human rights for prison inmates.

PMID- 23128521
TI  - [Clinical case: severe attack of psoriasis in an HIV infected patient].
AB  - Psoriasis, which does not appear to have greater prevalence amongst HIV+
      patients, does however present in its progress significant differences in these
      cases that are not only linked to immunodepression, but also to action of the
      virus itself on factors that aggravate psoriasis, such as the stimulation of
      keratinocytes, the favouring of skin infections, or the liberation of substance
      P, which also encourages growth in keratinocytes. A clinical case is presented
      along with explanatory imagess.

PMID- 23128523
TI  - The Supreme Court decision: a victory for uninsured patients.

PMID- 23128522
TI  - Norcantharidin suppresses cell growth and migration with enhanced anticancer
      activity of gefitinib and cisplatin in human non-small cell lung cancer cells.
AB  - Norcantharidin is the demethylated analog of cantharidin isolated from blister
      beetles (Mylabris phalerata Pall.). In this study, we evaluated whether
      norcantharidin exhibits anticancer effects against the human non-small cell lung
      cancer cell lines A549 (epidermal growth factor receptor (EGFR) mutation
      negative) and PC9 (EGFR mutation-positive). Our results revealed that
      norcantharidin dose-dependently retards cell growth, arrests cell cycle at G2/M
      phase, reduces cell migration, and even induces apoptosis at the concentration of
      100 uM. Moreover, we found that norcantharidin enhances the anticancer effects of
      gefitinib and cisplatin. Norcantharidin exhibited similar potency of anticancer
      effects against the two cell lines with different EGFR mutation status and did
      not affect EGF-induced EGFR phosphorylation, suggesting that the EGFR signaling
      may not be the target of norcantharidin. In conclusion, our results suggest that
      norcantharidin exhibits anticancer effects against non-small cell lung cancer
      cells in vitro and support its potential as a chemotherapeutic agent for treating
      non-small cell lung cancer.

PMID- 23128524
TI  - Effect of redox proteins on the behavior of non-volatile memory.
AB  - We demonstrated the memory effect of redox proteins in organic field-effect
      transistor (OFET) flash memory devices. Redox proteins include a heme structure,
      which has reversible redox reactions. These properties of the proteins could be
      successfully applied to the flash memory devices, which show a considerable
      memory window (~11 V) and relatively good endurance properties (~over 100
      cycles).

PMID- 23128525
TI  - Clinical Reflection:  a vital process for supporting the development of wisdom in
      doctors.
AB  - PURPOSE OF REVIEW: This review explores in detail the practice of reflection and
      its importance for doctors. It offers a definition of and a framework for both
      oral and written Clinical Reflection. It presents a thorough and detailed
      explanation of Clinical Reflection, its meaning, purpose, and processes and
      provides an illustrative case example from critical care. RECENT FINDINGS:
      Detailed reflection about clinical practice is now demanded by all postgraduate
      medical curricula and is beginning to be a requirement for annual appraisal.
      Doctors have been slow to develop reflective practice for themselves, tending to
      adopt methods from other healthcare professionals, because there is little in
      print to guide this process in relation to medical practice. SUMMARY: Clinical
      Reflection offers doctors a powerful way of supporting their professional
      development and providing evidence of their practical wisdom as expressed by
      Aristotle. It is time that an appropriate understanding of what reflection can
      offer doctors is explored more generally among the profession.

PMID- 23128526
TI  - Renal replacement therapy in the critically ill:  getting it right.
AB  - PURPOSE OF REVIEW: Survival of critically ill patients with severe acute kidney
      injury is still low. The aim of this review is to describe recent scientific
      evidence on renal replacement therapy (RRT) and its potential implications for
      future research and clinical practice. RECENT FINDINGS: Timing, dose and special
      indications of RRT will be described: recent literature provided new answers and
      new controversies about these three topics. SUMMARY: Specific research on RRT
      timing will be mandatory in the next few years: a standard definition of timing
      will certainly help to shed new light on how to improve RRT patients' outcome.
      Dialytic dose of continuous RRT has been recently and definitely standardized to
      20-25  ml/kg per hour (dialysis or hemofiltration), however, application to
      clinical practice still needs to be improved and new evidence on net
      ultrafiltration prescription showed that fluid balance may be as important as
      blood purification in critically ill patients with renal dysfunction. Special
      settings such as septic RRT, pediatric RRT, and RRT during extracorporeal
      membrane oxygenation recently achieved important results and new applications in
      clinical practice with important consequences for technical improvement and
      future care of these patients.

PMID- 23128527
TI  - Human NRDRB1, an alternatively spliced isoform of NADP(H)-dependent retinol
      dehydrogenase/reductase enhanced enzymatic activity of benzil.
AB  - AIMS: Human NRDRB1, a 226 amino acid alternatively spliced isoform of the NADP(H)
      dependent retinol dehydrogenase/reductase (NRDR), lacks the complete coding
      region of exon 3, but preserves all the important functional motifs for NRDR
      catalytic activity. Nevertheless, its tissue distribution and physiological
      function remain to be elucidated. METHODS: Expression of NRDRB1 and NRDR in cells
      and tissues was analyzed by semi-quantitative polymerase chain reaction (PCR) and
      western blot. NRDRB1 was expressed as a His(6) fusion protein and subjected to
      kinetics assays. RESULTS: Recombinant NRDRB1 had 1.2 to 8.6 fold higher
      k(cat)/K(m) values than recombinant NRDR, depending on the substrate. NRDRB1
      catalyzed the NADPH-dependent reduction of alpha-dicarbonyl compounds, such as
      isatin, 9,10-phenanthrenequinone, and especially benzil. The significantly high
      catalytic activity and the relatively high expression in human liver of NRDRB1
      conferred cellular resistance to benzil-induced cell toxicity and over-expression
      of NRDRB1 in low expressing Ec109 cells significantly enhanced cell tolerance
      toward benzil. CONCLUSIONS: Based on its substrate specificity, catalytic
      activity and relatively high expression in human liver tissue, our results
      suggest that NRDRB1, an alternatively spliced isoform of NRDR in vivo functions
      better than NRDR as a dicarbonyl reductase for xenobiotics containing reactive
      carbonyls. Our study is the first reporting this phenomenon of the enzymes
      involved in biochemical reactions.

PMID- 23128529
TI  - Endonasal dacryocystorhinostomy in a pediatric patient with ectrodactyly
      ectodermal dysplasia after failure of external dacryocystorhinostomy and as first
      procedure.
AB  - A 9-year-old patient affected by ectrodactyly-ectodermal dysplasia was referred
      to our clinic complaining of epiphora in both eyes. She had previous external
      dacryocystorhinostomy in her left eye. Ophthalmic examination revealed absence of
      the superior tear ducts and discharge in both eyes. Lacrimal irrigation through
      the inferior canaliculi revealed nasolacrimal duct obstruction on both sides. A
      bilateral endo-dacryocystorhinostomy was performed as a revision procedure in the
      left eye and as first procedure in the right eye. A monocanalicular silicone
      stent through the inferior tear duct was introduced on both sides at the end of
      the surgery. Follow up was 8 and 5 months for the left and the right eye,
      respectively. Epiphora was absent, and lacrimal irrigation showed a patent osteum
      at last follow-up. This case suggests that endo-dacryocystorhinostomy seems to be
      a safe and effective procedure, both as revision and as first procedure, even in
      children with ectrodactyly-ectodermal dysplasia.

PMID- 23128528
TI  - DNA methylation of the p14ARF, RASSF1A and APC1A genes as an independent
      prognostic factor in colorectal cancer patients.
AB  - We quantitated the methylated fraction of CpG sites in the promoter regions of O6
      MGMT, p14ARF, p16INK4a, RASSF1A and APC1A in tumor tissue from patients with
      colorectal cancer (CRC) in order to determine if promoter hypermethylation of any
      of these genes predicts survival. DNA was isolated from 111 primary CRC and 46
      matched normal colorectal mucosa samples from the same patients, obtained at
      primary surgery and DNA methylation was examined by Pyrosequencing(r). Follow-up
      time was up to 20 years. Patients showed partial promoter methylation in the
      following frequencies: O6-MGMT, 34%; p14ARF, 29%; p16INK4a, 28%; RASSF1A, 14%;
      and APC1A, 27%. Normal mucosa was always unmethylated. CRC patients with
      methylated p14ARF gene promoter had significantly worse prognosis (p=0.036),
      whereas those with methylated O6-MGMT had significantly better prognosis through
      the first 60 months post-treatment (RR 0.36; p=0.023). Methylation of one or more
      of the genes from the set p14ARF, RASSF1A and APC1A, was significantly (p=0.021)
      associated with worse prognosis even adjusting for tumor stage and
      differentiation (RR 2.2, p=0.037). Thus, DNA methylation of the p14ARF, RASSF1A
      and APC1A genes, diagnosed by Pyrosequencing, defines a poor prognosis subset of
      CRC patients independently of both tumor stage and differentiation. O6-MGMT
      methylation may play a protective role.

PMID- 23128530
TI  - Elephantoid eyelid edema associated with continuous positive airway pressure
      treatment.
AB  - A man with rosacea developed bilateral eyelid edema from wearing a continuous
      positive airway pressure nasal mask daily. The edema was refractory to steroid,
      diuretics, and lymphatic drainage massage. The effect may be related to
      cumulative venous congestion and lymphostasis due to the continuous positive
      airway pressure treatment.

PMID- 23128531
TI  - Orbital decompression to alleviate intermittent globe subluxation due to massive
      optic nerve sheath enlargement from chronic hydrocephalus.
AB  - A 59-year-old man with a history of chronic hydrocephalus and lifelong poor
      vision was referred to the oculoplastic surgery service for the management of
      symptomatic proptosis and intermittent globe subluxation of his OD. Imaging
      studies of his orbits revealed massively enlarged and calcified optic nerve
      sheaths. Neurosurgical consultation recommended against violation of the
      cerebrospinal fluid space given the chronic compensated hydrocephalus. Three-wall
      bony orbital decompression was therefore performed without complication and
      resulted in improved symptomatic and cosmetic outcomes.

PMID- 23128532
TI  - Giant dacryocystocele and congenital alacrimia in lacrimo-auriculo-dento-digital
      syndrome.
AB  - The lacrimo-auriculo-dento-digital syndrome, also known as Levy-Hollister
      syndrome, is a rare multiple congenital dysplasia characterized by malformation
      of the lacrimal apparatus and by aural, dental, and digital anomalies. Since the
      first report in 1973, different clinical findings such as urogenital
      malformations and facial dysmorphism have been described in the affected
      patients, showing that the phenotypic spectrum of the syndrome is broad. The
      authors report for the first time an association among giant dacryocystocele,
      alacrima, and agenesis of the lacrimal puncta in a patient with lacrimo-auriculo
      dento-digital syndrome.

PMID- 23128533
TI  - Inferomedial dermolipoma with ectopic lacrimal gland.
AB  - A 25-year-old woman presented with a painless inferomedial subconjunctival mass
      in the right eye. The growth had been present since birth and had been increasing
      in size for over 1 year. Incisional biopsy with debulking proved the lesion to be
      a dermolipoma extending behind the globe that contained ectopic lacrimal gland
      tissue. The authors describe a very rare case of a complex dermolipoma arising in
      an atypical location and containing ectopic lacrimal gland.

PMID- 23128534
TI  - Trigemino-abducens synkinesis after lateral orbitotomy.
AB  - A 30-year-old man underwent lateral orbitotomy with removal of dermoid cyst in
      the right orbit. One month after operation, the patient started to experience
      double vision. He had 25 prism diopters of esotropia in primary gaze with marked
      limitation of abduction in the right eye. Seven months after the operation, he
      developed synkinetic movement of the eye when clenching his teeth. He could
      abduct his right eye while gritting his teeth. This is the fourth reported case
      of trigemino-abducens synkinesis and the first reported case without brain
      trauma.

PMID- 23128535
TI  - Endoscopic transcanalicular diode laser dacryocystorhinostomy:  is it an
      alternative method to conventional external dacryocystorhinostomy?
AB  - PURPOSE: To compare the success rates of endoscopic transcanalicular diode laser
      dacryocystorhinostomy (EL-DCR) and external DCR. MATERIALS AND METHODS:
      Operations were performed on 55 eyes of 54 patients who had distal nasolacrimal
      canal obstruction. External DCR was performed on 29 of the eyes and EL-DCR on 26
      of them. Success was defined based on subjective relief of patients reported at
      their final examinations. RESULTS: There were 23 women and 6 men in group 1 and
      19 women and 6 men in group 2 (p = 0.77). The mean ages of groups were 45.24 +/-
      12.08 (range, 15-74) and 43.2 +/- 17.01 (range, 11-72) years, respectively (p =
      0.63). The mean follow-up times were 8.82 +/- 5.51 (range, 3-18) and 7.12 +/-
      2.96 (range, 2-12) months, respectively in groups (p = 0.58). The success rates
      based on symptoms were measured at 25 of 29 (86%) and 17 of 25 (68%) for 2
      groups. The difference in the success rates was higher but not found to be
      statistically significant (p = 0.202). The authors found various conditions
      related to nasal passage in 4 of 8 unsuccessful EL-DCR, including allergic
      rhinitis, nasal crust, silicone tube reaction, and unsuitable passage for
      endoscopic surgery. CONCLUSIONS: The success rate of EL-DCR was lower than that
      of the external DCR; however, no statistically significant difference was
      observed. Endoscopic transcanalicular diode laser DCR may be considered as an
      alternative method to external DCR with these results.

PMID- 23128536
TI  - Orbital cellulitis complicated by central retinal artery occlusion.
AB  - The authors present a case of a 16-year-old boy who sought treatment in Storm Eye
      Institute for orbital cellulitis complicated by central retinal artery occlusion.
      He was examined for severe signs of orbital cellulitis, including decreased
      vision and an afferent pupillary defect. Intravenous antibiotics failed to
      provide timely improvement, and the patient was surgically managed with
      endoscopic orbital decompression. An ocular examination under anesthesia revealed
      retinal ischemia in the affected eye, and fluorescein angiography confirmed the
      diagnosis of central retinal artery occlusion. The patient's vision improved
      slightly following resolution of the infection. Central retinal artery occlusion
      is a rare complication of orbital cellulitis in adults and has yet to be reported
      in the pediatric population.

PMID- 23128537
TI  - Electronically assisted nasolacrimal duct silicone intubation.
AB  - PURPOSE: Nasolacrimal duct intubation (NLDI) with silicone stents is a common
      procedure used by general ophthalmologists, oculoplastic surgeons, and
      otolaryngologists, among others. The procedure can be difficult to teach and to
      master. The authors investigated the usefulness and safety of an electronic
      device to aid endonasal retrieval of the lacrimal stent used in NLDI. METHODS: A
      prospective interventional surgical technique case series was designed and
      executed with institutional review board approval. Twelve adult patients who were
      scheduled to undergo NLDI were enrolled. The audible alarm device was used during
      endonasal retrieval of the probe in each patient. Each patient underwent
      intraoperative rigid nasal endoscopy at the conclusion of the case. RESULTS: The
      electronic device successfully localized the endonasal probe in each patient.
      Nasal endoscopy revealed healthy mucosa with no evidence of thermal or electrical
      injury. CONCLUSIONS: Electronically assisted NLDI with audible feedback is a
      small technological advance with potential to improve the safety and efficacy of
      NLDI. The technique is safe and effective in localizing the intranasal portion of
      a metal lacrimal probe. Further testing will assess its usefulness in complex
      cases and as a teaching tool.

PMID- 23128538
TI  - Intraglandular injection of botulinum toxin a reduces tear production in rabbits.
AB  - PURPOSE: To develop an animal model and investigate the dose-dependent effect of
      an intraglandular injection of botulinum toxin A (BTX-A) on tear production.
      METHODS: In a volume of 0.1-ml, 0.625-, 1.25-, or 2.5-U BTX-A was injected
      transconjunctivally in the superolateral lobe of the lacrimal gland of adult New
      Zealand white female rabbits. In the contralateral lacrimal gland, 0.1 ml of 0.9%
      sodium chloride was injected. Prior to injection and at 1-week postinjection,
      photographs were taken to evaluate pre- and postoperative eyelid position.
      Fluorescein and Rose Bengal stain were used to evaluate the corneal surface, and
      Schirmer test was used to assess tear production. RESULTS: Glands injected with
      the intermediate (1.25 U) and the highest (2.5 U) doses of BTX-A displayed a
      statistically significant decrease in tear production (p = 0.002 and 0.007,
      respectively) compared with the contralateral saline-injected glands at 1 week.
      No corneal pathologic factors from excessive dryness were observed following the
      injection. While postinjection ptosis was observed (p = 0.025), no difference was
      seen between BTX-A and saline-injected eyes. CONCLUSIONS: In rabbits,
      intraglandular injection of BTX-A resulted in decreased tear production at 1
      week. No additional reduction in tear production was seen with a BTX-A dose
      greater than 1.25 U, suggesting glandular receptor saturation at this dose.
      Despite suppression of tear production, no corneal pathologic factors were
      observed. Further studies are needed to refine this animal model with the
      ultimate goal of determining optimum delivery route and concentration to
      reduction in tear production while minimizing side effects in patients.

PMID- 23128539
TI  - Arcanobacterium hemolyticum orbital cellulitis: a rare but aggressive disease.
AB  - The clinical presentation and course of orbital cellulitis in a young adult
      resulting from Arcanobacterium hemolyticum frontal sinusitis are presented in
      detail. This case illustrates the importance of a multidisciplinary approach for
      refractory and aggressive orbital cellulitis. A high level of suspicion for A.
      hemolyticum must be maintained in such cases, because it has proven to be a rare
      but aggressive, potentially occult, and life-threatening pathogen.

PMID- 23128541
TI  - Poor zinc status in early infancy among both low and normal birth weight infants
      and their mothers in Delhi.
AB  - BACKGROUND: Low birth weight (LBW) infants are at high risk of zinc deficiency,
      but there is a paucity of data on their zinc status. OBJECTIVE: To evaluate zinc
      status of LBW (BW <2,500 g) and normal birth weight (NBW; BW >= 2,500 g) infants
      at birth and in early infancy. METHODS: A total of 339 infants (LBW, n = 220;
      NBW, n = 119) were enrolled, and venous blood samples of mother-infant dyad were
      taken within 48 h of birth. Infants' levels were repeated between 2 and 10 months
      of age. Serum zinc levels were estimated using an inductively coupled plasma mass
      spectrometer. Primary outcome was zinc deficiency, defined as serum zinc <65
      ug/dl. RESULTS: Zinc results were available for 182 LBW and 103 NBW infants at
      birth and for 100 LBW and 66 NBW infants at follow-up with a median postnatal age
      of 14 and 15.5 weeks, respectively. Median zinc levels were low and comparable at
      birth as well as at follow-up, with zinc deficiency being present in 51.0% of LBW
      and 42.4% of NBW infants at birth and in 79.0% of LBW and 66.7% of NBW infants at
      follow-up. Zinc levels decreased significantly in both groups from birth to
      follow-up, irrespective of zinc multivitamin supplementation. Zinc levels of
      infants with BW <2,000 g at follow-up were significantly lower compared to
      infants with higher BW. CONCLUSION: Zinc status was poor in many infants at birth
      irrespective of BW. Zinc status worsened significantly during early infancy, with
      infants with BW <2,000 g having the lowest zinc levels.

PMID- 23128542
TI  - Determinants of coronary collateral circulation in patients with coronary artery
      disease.
AB  - OBJECTIVE: This study aims to identify possible determinants of coronary
      collaterals in patients with severe coronary artery disease. METHODS: The current
      study has a retrospective cohort design. Seventy four patients with >=90%
      stenosis or total occlusion of the left anterior descending artery (LAD) were
      enrolled; coronary collateral grades, high-sensitive C-reactive protein (hs-CRP),
      fibrinogen, protein C and S, lipids, uric acid levels and medications applied
      before coronary angiography were noted and compared. Multiple logistic regression
      analysis was used for the multivariate analyses of independent variables
      associated with the development of adequate coronary collateral vessels. RESULTS:
      The presence of coronary collaterals was significantly higher in males (p=0.018),
      with higher hs-CRP (p=0.023), prior statin use (p=0.022), and higher Gensini
      scores (p<0.001). In multiple logistic regression analysis, hs-CRP levels
      (OR=0.94, 95.0% CI=0.883-1.000, p=0.048), male gender (OR=4.73, 95.0% CI=1.441
      15.539, p=0.010) and prior statin usage (OR=4.70, 95.0% CI=1.264-17.452, p=0.021)
      were identified as independent predictors of coronary collateral development.
      CONCLUSION: Male gender, prior statin usage, and higher hs-CRP levels are
      determinants of coronary collaterals in patients with coronary artery disease.

PMID- 23128543
TI  - Reel syndrome: dislodgement of an active fixation lead.

PMID- 23128544
TI  - Successful percutaneous balloon mitral valvuloplasty in patients with left atrial
      appendage thrombus.

PMID- 23128545
TI  - The role of two-dimensional speckle-tracking echocardiography in a patient with
      Behcet's disease.

PMID- 23128546
TI  - Aneurysm of ascending and descending aorta in a 10-year-old-boy with Wiskott
      Aldrich syndrome.

PMID- 23128547
TI  - Vacuum-assisted closure for skin infection in a patient with Berlin Heart Excor
      biventricular assist device.

PMID- 23128548
TI  - Giant left main coronary artery aneurysm complicated with anterior myocardial
      infarction in Behcet's syndrome.

PMID- 23128549
TI  - Controlled removal of a dislodged stent causing myocardial ischemia 1 year after
      stent placement.

PMID- 23128550
TI  - Three-dimensional transesophageal echocardiographic evaluation of a patent
      foramen ovale accompanied with interatrial septal space.

PMID- 23128551
TI  - Accordion-like giant interatrial septal aneurysm.

PMID- 23128552
TI  - Huge caseous calcification of the mitral annulus mimicking cardiac mass presented
      with atrioventricular block and severe mitral regurgitation.

PMID- 23128553
TI  - Three-dimensional echocardiographic evaluation of an anterior mitral leaflet
      perforation and aortic vegetation due to infective endocarditis.

PMID- 23128554
TI  - Prosthetic mitral valve obstruction: diagnosis with real-time three-dimensional
      transesophageal echocardiography.

PMID- 23128555
TI  - Synthesis and asymmetric hydrogenation of (3E)-1-benzyl-3-[(2-oxopyridin-1(2H)
      yl)methylidene]piperidine-2,6-dione.
AB  - The synthesis of (3E)-1-benzyl-3-[(2-oxopyridin-1(2H)-yl)methylidene]piperidine
      2,6-dione 5 from N-benzylglutarimide was achieved in three steps. The asymmetric
      hydrogenation of 4 gave either the product of partial reduction (10) or full
      reduction (13), depending on the catalyst which was employed, in high ee in each
      case. Attempts at asymmetric transfer hydrogenation (ATH) of resulted in
      formation of a racemic product.

PMID- 23128556
TI  - Giant craniopharyngioma presenting as a cerebellopontine angle tumour.

PMID- 23128557
TI  - Metabolic flux ratio analysis and multi-objective optimization revealed a
      globally conserved and coordinated metabolic response of E. coli to paraquat
      induced oxidative stress.
AB  - The ability of a microorganism to adapt to changes in the environment, such as in
      nutrient or oxygen availability, is essential for its competitive fitness and
      survival. The cellular objective and the strategy of the metabolic response to an
      extreme environment are therefore of tremendous interest and, thus, have been
      increasingly explored. However, the cellular objective of the complex regulatory
      structure of the metabolic changes has not yet been fully elucidated and more
      details regarding the quantitative behaviour of the metabolic flux redistribution
      are required to understand the systems-wide biological significance of this
      response. In this study, the intracellular metabolic flux ratios involved in the
      central carbon metabolism were determined by fractional (13)C-labeling and
      metabolic flux ratio analysis (MetaFoR) of the wild-type E. coli strain JM101 at
      an oxidative environment in a chemostat. We observed a significant increase in
      the flux through phosphoenolpyruvate carboxykinase (PEPCK), phosphoenolpyruvate
      carboxylase (PEPC), malic enzyme (MEZ) and serine hydroxymethyltransferase
      (SHMT). We applied an epsilon-constraint based multi-objective optimization to
      investigate the trade-off relationships between the biomass yield and the
      generation of reductive power using the in silico iJR904 genome-scale model of E.
      coli K-12. The theoretical metabolic redistribution supports that the trans
      hydrogenase pathway should not play a direct role in the defence mounted by E.
      coli against oxidative stress. The agreement between the measured ratio and the
      theoretical redistribution established the significance of NADPH synthesis as the
      goal of the metabolic reprogramming that occurs in response to oxidative stress.
      Our work presents a framework that combines metabolic flux ratio analysis and
      multi-objective optimization to investigate the metabolic trade-offs that occur
      under varied environmental conditions. Our results led to the proposal that the
      metabolic response of E. coli to paraquat-induced oxidative stress is globally
      conserved and coordinated.

PMID- 23128558
TI  - Investigation of nebivolol as a novel therapeutic agent for the treatment of
      Alzheimer's disease.
AB  - Nebivolol is a selective beta1 adrenergic receptor antagonist with nitric oxide
      mediated vasodilatory properties utilized in the treatment of hypertension.
      Previously, nebivolol was shown to modulate amyloid-beta protein precursor
      processing in vitro. In this study, we investigated the in vivo effects of
      nebivolol on the modulation of amyloid neuropathology in the Tg2576 mouse model
      of Alzheimer's disease (AD). We found that nebivolol is brain bioavailable and
      can be readily detected in the brain following three weeks of treatment at a dose
      of 1 mg/kg/day. Moreover, this treatment regime resulted in a significant
      reduction of amyloid-beta neuropathology in the brain, and this reduction was
      inversely correlated with plasma levels of amyloid-beta. Chronic nebivolol
      treatment of Tg2576 mice with established amyloid neuropathology and cognitive
      impairments significantly reduced brain amyloid content but failed to improve
      cognitive function. Our study demonstrates that nebivolol is highly tolerable and
      safe and can significantly reduce amyloid neuropathology in the brain, which
      could be one of the most important parameters for primary prevention of AD. Our
      studies support the continued investigation of nebivolol for the treatment of AD
      at very early stages of the disease.

PMID- 23128559
TI  - Clinical differences in patients with Alzheimer's disease according to the
      presence or absence of anosognosia: implications for perceived quality of life.
AB  - This study aimed to determine the factors that predict anosognosia in patients
      with Alzheimer's disease (AD) and to examine the effect of anosognosia on patient
      and caregiver perceptions of the patient's quality of life (QoL-p), using a cross
      sectional design with 164 patients and their caregivers. Instruments of
      measurement included Anosognosia Questionnaire-Dementia, Geriatric Depression
      Scale, Quality of Life in AD (QoL-AD), Disability Assessment for Dementia,
      Neuropsychiatric Inventory, and the Global Deterioration Scale (GDS). A binary
      logistic regression analysis was performed to identify the factors that predict
      anosognosia, while a linear regression analysis was conducted to determine the
      factors associated with QoL-AD. The degree of anosognosia increased in line with
      GDS stage (F (2,161) = 41.3, p < 0.001). In the binary regression analysis, the
      variables that predicted anosognosia were more neuropsychiatric symptoms (OR =
      1.11, 95% CI: 1.06-1.17, p < 0.001), deficits in ADL (OR = 0.88, 95% CI: 0.83
      0.94, p < 0.001), less depression (OR = 0.66, 95% CI: 0.54-0.82, p < 0.001), and
      older age (OR = 1.08, 95% CI: 1.00-1.15, p = 0.027). With regards to QoL-p, the
      multiple linear regression analysis for patients (r2 = 0.486) showed that less
      depression (beta = -0.52, p < 0.001) and greater anosognosia (beta = 0.40, p <
      0.001) explained 33% and 10% of the variance in QoL-AD, respectively. Greater
      anosognosia was associated with better perceived QoL-p, especially in advanced
      GDS stages. Anosognosia was associated with greater caregiver burden and a
      greater discrepancy between patient and caregiver ratings of QoL-p.

PMID- 23128560
TI  - The impact of early versus late surgical decompression on neurological recovery
      after traumatic spinal cord injury (SCI).

PMID- 23128561
TI  - Role of the JAK/STAT signaling pathway in the pathogenesis of acute myocardial
      infarction in rats and its effect on NF-kappaB expression.
AB  - The Janus kinase/signal transducer and activator of transcription pathway
      (JAK/STAT signaling pathway) is involved in the development of numerous
      cardiovascular diseases, although the specific role of this pathway in the
      pathogenesis of acute myocardial infarction (AMI) has not been elucidated. The
      purpose of this study was to evaluate the role of the JAK/STAT signaling pathway
      in the onset of AMI in rats. We also tested the effect of this pathway on nuclear
      factor kappaB (NF-kappaB) expression in the myocardium and tumor necrosis factor
      alpha (TNF-alpha) levels in the plasma of AMI rats. An AMI rat model was
      successfully established and AG490 was used to block the JAK/STAT signaling
      pathway. The plasma TNF-alpha levels of AMI rats were measured by ELISA. The
      protein expression of NF-kappaB in the myocardial cells of AMI rats was detected
      by immunohistochemistry. The infarction area was significantly smaller in rats
      treated with AG490 after coronary artery ligation (group C) compared with that in
      the myocardial infarction control group (group B). The left ventricular mass
      indices in the sham surgery group (group A) and group C were significantly lower
      compared with those of group B. Plasma TNF-alpha concentrations in group B were
      significantly higher compared with those of groups A and C. There were
      significantly fewer cardiomyocytes positively exhibiting NF-kappaB protein
      expression in groups A and C compared with group B. The JAK/STAT signaling
      pathway is involved in the onset of myocardial infarction and may also be
      involved in left ventricular remodeling after myocardial infarction. The
      involvement of the JAK/STAT signaling pathway in the onset of myocardial
      infarction may be correlated with its effects on the expression of NF-kappaB and
      TNF-alpha. 

PMID- 23128562
TI  - [The Spanish experience: a comprehensive approach to HIV and HCV in prisons].

PMID- 23128563
TI  - [Consensus document for the control of tuberculosos in Spanish prisons].

PMID- 23128564
TI  - [Multi-centre study of the prevalence of latent tuberculosis infection amongst
      inmates in Spanish prisons].
AB  - AIMS: To study the prevalence of latent tuberculosis infection (LTBI) amongst
      inmates in Spanish prisons. MATERIALS AND METHODS: Multi-centre, cross-sectional
      study; two stage sampling. Socio-demographic, prison and clinical variables were
      gathered. A univariate, bivariate and multivariate analysis was carried out using
      logistic regression with the variables that showed statistical significance. The
      odds ratio was calculated with a confidence interval of 95%. RESULTS: 378
      patients. The Mantoux test (PPD) assessable in 90.2% was available. 91.2% men,
      37.8% foreigners with average age of 35.9+/-10.3 years. Average stay in prison: 2
      years, 28.7% had been > 5 years in prison. 49.6% entered prison in 2006 or
      before. 24.5% had a history of intravenous drug use (IDU). 50.4% presented LTBI
      that was associated with: age > 40 years (63.2 vs 43.8%; CI: 1.39-3.49; OR: 2.20;
      p=0.001); stay of > 5 years in prison (71.2 vs 41.3%; CI: 2.13-5.75; OR: 3.50;
      p<0.001); in prison since 2006 or before (58.1 vs 42.6%; CI: 1.22-2.88; OR:1.87;
      p=0.004); infected with HCV+ (66.3 vs 45.3%; CI:1.40-4.0; OR: 2.37; p=0.001). The
      logistic regression model confirmed the independent association of LTBI with: a)
      age > 40 years (OR: 1.76; CI: 1.08-2.87; p=0.024); and length of prison stay > 5
      years (OR: 2.50; CI: 1.41-4.43; p=0.002). CONCLUSIONS: The prevalence of LTBI in
      prison is very high, especially amongst inmates over 40 and those who have been
      in prison for more than five years. To prevent the risk of progression to
      tuberculosis, treatment is recommended for those who require it along with the
      maintenance of control programmes for this pathology.

PMID- 23128565
TI  - [Results of the Spanish experience: a comprehensive approach to HIV and HCV in
      prisons].
AB  - AIMS: to measure the results of prevention, health promotion and damage reduction
      programs for the health of the prison population via the progress of a number of
      illnesses in these contexts. MATERIALS AND METHODS: The information was taken
      from reports, bulletins, specifications, central records and other documents
      containing health information from 1993 to 2009 RESULTS: The prevalence of HIV
      has diminished 3.5 times and HCV has gone down by 50% in the last ten years. The
      rates of seroconversion within prisons have gone down by 85% in the case of HIV
      and by 71% for HCV. The incidence of tuberculosis and AIDS has decreased by 85%
      and 93.7% respectively. The number of users of damage reduction, methadone
      maintenance and syringe exchange programs has progressively increased to the
      point where the number of IDUs has begun to diminish, while the health mediators
      program has been implemented in practically all prisons. DISCUSSION: In response
      to WHO criteria, a series of activities were set in motion in the 90s by prisons,
      which focused on improving the situation of the prison population, including
      illness prevention and control, and damage reduction and health promotion
      programs. These have significantly contributed to improving the health of a
      population that comes from what only can be regarded as a highly vulnerable
      situation outside prison.

PMID- 23128566
TI  - [Multi-drug resistant and extremely drug resistant].

PMID- 23128567
TI  - [Not Available].

PMID- 23128568
TI  - The effect of values affirmation on race-discordant patient-provider
      communication.
AB  - BACKGROUND: Communication between African American patients and white health care
      providers has been shown to be of poorer quality when compared with race
      concordant patient-provider communication. Fear on the part of patients that
      providers stereotype them negatively might be one cause of this poorer
      communication. This stereotype threat may be lessened by a values-affirmation
      intervention. METHODS: In a blinded experiment, we randomized 99 African American
      patients with hypertension to perform a values-affirmation exercise or a control
      exercise before a visit with their primary care provider. We compared patient
      provider communication for the 2 groups using audio recordings of the visit
      analyzed with the Roter Interaction Analysis System. We also evaluated visit
      satisfaction, trust, stress, and mood after the visit by means of a
      questionnaire. RESULTS: Patients in the intervention group requested and provided
      more information about their medical condition (mean [SE] number of utterances,
      66.3 [6.8] in the values-affirmation group vs 48.1 [5.9] in the control group [P
      = .03]). Patient-provider communication in the intervention group was
      characterized as being more interested, friendly, responsive, interactive, and
      respectful (P = .02) and less depressed and distressed (P = .03). Patient
      questionnaires did not detect differences in visit satisfaction, trust, stress,
      or mood. Mean visit duration did not differ significantly between the groups
      (19.2 minutes in the control group vs 20.5 minutes in the intervention group [P =
      .29]). CONCLUSIONS: A values-affirmation exercise improves aspects of patient
      provider communication in race-discordant primary care visits. The clinical
      impact of the intervention must be defined before widespread implementation can
      be recommended.

PMID- 23128570
TI  - Alcohol use and hazardous drinking among medical specialists.
AB  - BACKGROUND: Alcohol use among medical specialists remains a delicate topic.
      However, the number of prevalence studies remains very limited in Western
      European countries. AIMS: To explore alcohol use and hazardous drinking among
      male and female medical specialists. METHODS: All medical specialists in Belgium-
      a typical Western European country regarding alcohol use--were invited to
      participate. Alcohol use and abuse were measured using the Alcohol Use Disorder
      Identification Test (AUDIT) and the CAGE screen (acronym based on the four items
      it contains: 'Cut down drinking', 'Annoyed by criticism', 'Guilty feelings' and
      'Eye opener'). RESULTS: A sample of 1,501 specialists completed the survey. The
      composition of the sample was comparable with that of the overall population of
      specialists in Belgium regarding gender, age and specialties. A proportion of 18%
      of the specialists could be classified as hazardous drinkers and 16.8% reported
      binge drinking at least once a month. Female medical specialists drank less than
      their male counterparts; however, a substantial proportion of female specialists
      (14.9%) displayed higher risk levels of hazardous drinking. Significant
      differences were found between specialties on the CAGE screen. Finally, younger
      medical specialists tended to display healthier alcohol use patterns compared
      with their older counterparts. CONCLUSION: Medical specialists tend to indulge in
      more hazardous drinking compared with the general population (10%). The alcohol
      use patterns of female doctors tend to move towards those of males.

PMID- 23128569
TI  - INSL5 is a novel marker for human enteroendocrine cells of the large intestine
      and neuroendocrine tumours.
AB  - We report for the first time the distribution of human INSL5 and its cognate
      leucine rich G-protein coupled receptor RXFP4 in the large intestine and in
      neuroendocrine/carcinoid tissues. Immunoreactive INSL5 was uniquely expressed by
      enteroendocrine cells (EECs) located within the colonic mucosa, whereas
      colonocytes were immunopositive for RXFP4. INSL5+ and RXFP4+ cells were also
      detected in human neuroendocrine/carcinoid tissues. We employed a recently
      described Insl5 knockout mouse model and 2 mouse models of induced colitis to
      address the relevance of Insl5 in EEC development and in acute inflammation of
      the colon. We identified INSL5 as a specific marker for synaptophysin+ EECs in
      the mucosa of the normal human and mouse colon. Insl5 was not essential for the
      development of mouse synaptophysin+ EECs. The mouse models of chemically induced
      colitis (dextran sulfate sodium and dinitrobenzene-sulfonic acid) failed to show
      changes in the numbers of Insl5+ EECs at inflammatory sites during the acute
      phase of colitis. In conclusion, we showed that INSL5 is a novel marker of
      colorectal EECs and provide first evidence for the presence of a potentially
      autocrine/paracrine INSL5-RXFP4 signaling system in the normal human and mouse
      colon and in rare human neuroendocrine tumours.

PMID- 23128571
TI  - BK virus-associated bilateral ureteric stenosis after haematopoietic SCT: viral
      kinetics and successful treatment.

PMID- 23128572
TI  - Survival benefits with transplantation in secondary AML evolving from
      myelodysplastic syndrome with hypomethylating treatment failure.
AB  - The prognosis for patients with myelodysplastic syndrome with hypomethylating
      treatment failure (MDS-HTF) has been known to be poor. However, the clinical
      outcomes and optimal treatment options for secondary AML evolving from MDS-HTF
      (sAML/MDS-HTF) are not well known. This retrospective analysis was conducted to
      evaluate the clinical outcomes and influences of treatment options on survival in
      46 consecutive patients with sAML/MDS-HTF. The median OS rates were 1.4 months in
      the best supportive care group (n=15) and 9.4 months in the active treatment
      group (n=31). One-year OS rates were 13.3% and 36.8%, respectively (P=0.001).
      Active treatment (P<0.001), lower BM blast (<33%) at sAML (P=0.007), non-poor
      NCCN (National Cancer Comprehensive Network) cytogenetics (P=0.001) and good
      performance status (ECOG (Eastern Cooperative Oncology Group) ?1) (P=0.024) were
      significant predictors affecting favorable OS in a multivariate analysis. Of the
      active treatment options, allo-SCT with prior chemotherapy (CTx) showed better OS
      compared with CTx only or SCT without CTx (P=0.019). Our analyses suggest that
      active treatment, particularly SCT following CTx, should be considered in
      patients with sAML/MDS-HTF if the patient is medically fit.

PMID- 23128573
TI  - Outcome of children who experience disease relapse following allogeneic
      hematopoietic SCT for hematologic malignancies.
AB  - Relapse after allogeneic hematopoietic SCT (HSCT) carries a poor prognosis and is
      a common cause of death. Outcomes of children who relapse post HSCT are not well
      known. In this retrospective multicenter study we included 532 patients who
      underwent allogeneic HSCT and examined the outcomes of 160 patients (30%) who
      relapsed. Treatment options after relapse included (i) palliative therapy with
      non-curative intent (n=43), (ii) salvage chemotherapy (without a second HSCT,
      n=55) or (iii) salvage chemotherapy followed by a second HSCT (n=62). Sixty two
      patients underwent a second HSCT. The 1-year disease-free survival (DFS) for
      those given palliative therapy, chemotherapy alone and who underwent a second
      transplant was <1%, 9% and 50% (P=<0.0001), respectively. The DFS at 1 and 2 year
      was 50% and 35%, respectively, among the patients who received a second
      transplant versus 9% and 2% in those who did not (P=<0.0001). In multivariable
      analysis longer time to relapse (P=0.04) and undergoing a second HSCT (P<0.001)
      were associated with improved outcome. Withdrawal of immunosuppressive therapy,
      followed by curative intent chemotherapy should be offered to all patients who
      relapse after an allogeneic HSCT. A second HSCT should be considered, especially
      in patients who respond to salvage chemotherapy.

PMID- 23128574
TI  - Hypoparathyroidism:  from diagnosis to treatment.
AB  - PURPOSE OF REVIEW: This review provides an update on hypoparathyroidism (HPT),
      focusing on the major aspects of diagnosis, clinical manifestations and
      management of patients with hypocalcaemia due to HPT. RECENT FINDINGS: Recent
      advances in the understanding of the physiologic actions of parathormone (PTH)
      and vitamin D, and the application of molecular genetics, have clarified certain
      aspects of the pathogenesis, classification, diagnosis and management of HPT.
      SUMMARY: PTH promotes bone resorption, decreases urinary calcium excretion,
      enhances the conversion of 25-hydroxyvitamin D to 1, 25-dihydroxyvitamin D and
      increases intestinal calcium absorption and phosphate renal excretion.
      Understanding the molecular cause of the disease in patients and their families
      has the potential for proper tailoring of genetic counselling, family screening
      and treatment. Signs and symptoms may be associated not only with the severity,
      chronicity and therapeutic endpoints in HPT but also with the different causes of
      the disease. Hypocalcaemia may be an asymptomatic laboratory finding or a life
      threatening metabolic disturbance. Although the therapy of acute hypocalcaemia is
      usually readily accomplished, chronic hypocalcaemia remains a very difficult
      treatment problem. Replacement therapy with PTH could be a therapeutic option for
      refractory HPT.

PMID- 23128575
TI  - Vitamin D action:  lessons learned from hereditary 1,25-dihydroxyvitamin-D
      resistant rickets patients.
AB  - PURPOSE OF REVIEW: Hereditary 1,25-dihydroxyvitamin-D [1,25(OH)(2)D(3)]-resistant
      rickets (HVDRR) is a rare genetic disease caused by generalized resistance to
      1,25(OH)(2)D(3). Less than 100 cases are reported in the literature. These
      patients provide an experiment by nature enabling us to understand the role of
      vitamin D, especially in light of the ongoing debate concerning normal vitamin D
      levels and the supplement dosage that should be recommended. This article
      summarizes the role of vitamin D in calcium absorption, rennin-angiotensin system
      (RAS), and cardiac state in HVDRR patients. RECENT FINDINGS: The precise spectrum
      of vitamin D activities can now be better evaluated by critical analysis of mouse
      models with targeted deletion of the gene encoding the vitamin D receptor (VDR).
      Of special interest is the unraveling of the role of VDR in calcium absorption
      and cardiac status in VDR-knockout mice. The facts that VDR-knockout mice up
      regulate intestinal calcium absorption and skeletal mineralization independently
      of the VDR during pregnancy and lactation point to the existence of VDR
      independent mechanisms that are involved in calcium absorption. The observation
      that mice with genetic disruption of the 1alpha-hydroxylase gene or of the VDR
      gene have an overstimulated RAS and consequently develop high blood pressure and
      cardiac hypertrophy raised concern about potential risks to the cardiovascular
      system in HVDRR patients. SUMMARY: The current review summarizes the new
      understanding of the effects of vitamin D on calcium absorption, the RAS, and
      heart hypertrophy derived from studying HVDRR patients from infancy to their mid
      30s.

PMID- 23128576
TI  - Use of bone turnover markers in clinical practice.
AB  - PURPOSE OF REVIEW: To describe the modalities and interest of the use of bone
      turnover markers (BTMs) in clinical practice for osteoporosis management. RECENT
      FINDINGS: Serum procollagen type I N-terminal propeptide and serum collagen type
      I crosslinked C-telopeptide are respectively the formation and resorption markers
      recommended to use as references for bone remodelling assessment in clinical
      studies. SUMMARY: Biochemical BTMs reflect changes in bone metabolism. In
      clinical practice, many factors influencing BTMs, variability needs to be
      integrated during all of the dosage process. They include sample collection and
      storage conditions, patient's characteristics and lifestyle habits, recent
      fracture. The reference intervals are also affected by the type of automated
      assays used to assess BTMs. Appropriate references measured with the same assay
      method must be used for the optimum interpretation of results. BTMs have been
      extensively used as indicators in the diagnosis and monitoring of osteoporosis.
      However, their interest was mainly demonstrated to reflect changes in bone
      metabolism under antiosteoporotic treatments in clinical studies. Significant
      reductions in BTMs associated with fracture risk reduction needs to be determined
      in the management of osteoporosis. The standardization of BTMs, assays with
      international reference standards should provide conditions to state on the
      applications of BTMs in routine clinical practice.

PMID- 23128577
TI  - Current world literature.

PMID- 23128579
TI  - Patient time costs associated with sensor-augmented insulin pump therapy for type
      1 diabetes: results from the STAR 3 randomized trial.
AB  - BACKGROUND: Sensor-augmented pump therapy (SAPT) leads to lower glycated
      hemoglobin levels than multiple daily injections of insulin (MDI) in patients
      with type 1 diabetes. Patient time and costs associated with SAPT are not known.
      OBJECTIVE: We compared time spent on diabetes-related care, changes in time, and
      associated patient time costs between patients randomly assigned to SAPT or MDI.
      DESIGN, SETTING, AND PARTICIPANTS. During a 52-week clinical trial, participants
      aged 7 to 70 years (n = 483) reported total time per week spent on diabetes
      related care. MEASUREMENTS: Patient time, including comparisons during pump
      initiation, 52-week patient time costs, and changes in weekly time estimates
      after pump initiation. RESULTS: At baseline, patients in the MDI group reported
      spending an average of 4.0 hours per week on diabetes-related care. During the
      pump initiation period (weeks 1-7), SAPT patients spent 1.9 hours more per week
      than MDI patients (95% confidence interval [CI], 1.2-2.6). After the initiation
      period (weeks 8-52), SAPT patients spent 1 hour more per week (95% CI, 0.4-1.7)
      than MDI patients (i.e., 4.4 v. 3.4 hours); patients in both groups spent
      progressively less time on diabetes-related care by 1.2 minutes per week (95% CI,
      -1.7 to -0.7). Overall, mean time costs per person were $4600 with the SAPT group
      and $3523 with the MDI group (difference, $1077; 95% CI, $491-$1638).
      LIMITATIONS: Time spent on specific activities was not collected, and the
      estimates do not explicitly account for caregiver time associated with diabetes
      care activities. CONCLUSIONS: Patients receiving SAPT v. MDI spent approximately
      2 hours more per week on diabetes-related care during pump initiation and 1 hour
      more per week thereafter, resulting in higher patient time costs.

PMID- 23128580
TI  - Patients' experiences of shared decision making in primary care practices in the
      United kingdom.
AB  - BACKGROUND: Shared decision making (SDM) and patient self-management support are
      key components of US and UK policy for chronic disease management, whereby SDM is
      seen as enhancing physician-patient negotiation around self-management. The WISE
      trial is implementing training in self-management support for primary care
      physicians in one UK region. This article describes preintervention levels of
      patient-reported SDM and explores how this varies with patient and practice
      characteristics. METHODS: We analyzed baseline data from a cluster randomized
      controlled trial for 2965 patients with diabetes, chronic obstructive pulmonary
      disease, and irritable bowel syndrome (IBS) from 29 family practices. Patient
      level measures included self-report of chronic conditions, SDM (Health Care
      Climate Questionnaire [HCCQ]), health status, and demographic characteristics.
      Area and practice characteristics included chronic disease workload and
      socioeconomic deprivation. RESULTS: The mean SDM score was 75 (out of 100), but
      the range was wide. The mean score was lower for IBS patients but did not vary
      with other disease conditions. Younger patients and those with poorer health
      status reported lower degrees of SDM. No associations were found with practice
      characteristics. LIMITATIONS: The study was restricted to one socioeconomically
      deprived region, and hence results may not be nationally representative of the
      United Kingdom. Ceiling effects on SDM scores may limit the utility of the HCCQ.
      CONCLUSIONS: Lower ratings from some patient groups may reflect differences in
      expectations rather than differences in physician behavior. Overall levels of SDM
      were high, and no patient or practice characteristic represented a serious
      barrier to SDM. However, we cannot say to what extent SDM in this chronic
      population addressed self-management issues rather than clinical care. More
      nuanced measures of SDM are required that distinguish between different forms of
      care.

PMID- 23128582
TI  - The role of hyphens at the constituent boundary in compound word identification.
AB  - The current eye-movement study investigated whether a salient segmentation cue
      like the hyphen facilitates the identification of long and short compound words.
      The study was conducted in Finnish, where compound words exist in great
      abundance. The results showed that long hyphenated compounds (musiikki-ilta) are
      identified faster than concatenated ones (yllatystulos), but short hyphenated
      compounds (ilta-asu) are identified slower than their concatenated counterparts
      (kesasaa). This pattern of results is explained by the visual acuity principle
      (<citationReference id="cr1-1" rid="c1">Bertram & Hyona,
      2003</citationReference>): A long compound word does not fully fit in the foveal
      area, where visual acuity is at its best. Therefore, its identification begins
      with the access of the initial constituent and this sequential processing is
      facilitated by the hyphen. However, a short compound word fits in the foveal
      area, and consequently the hyphen slows down processing by encouraging sequential
      processing in cases where it is possible to extract and use information of the
      second constituent as well.

PMID- 23128581
TI  - On averages and peaks: how do people integrate attitudes about multiple diseases
      to reach a decision about multiplex genetic testing?
AB  - BACKGROUND: The aim of the current study was to learn how people integrate
      attitudes about multiple health conditions to make a decision about genetic
      testing uptake. METHODS: This study recruited 294 healthy young adults from a
      parent research project, the Multiplex Initiative, conducted in a large health
      care system in Detroit, Michigan. All participants were offered a multiplex
      genetic test that assessed risk for 8 common health conditions (e.g., type 2
      diabetes). Data were collected from a baseline survey, a web-based survey, and at
      the time of testing. RESULTS: Averaging attitudes across diseases predicted test
      uptake but did not contribute beyond peak attitudes, the highest attitude toward
      testing for a single disease in the set. Peak attitudes were found sufficient to
      predict test uptake. LIMITATIONS: The effects of set size and mode of
      presentation could not be examined because these factors were constant in the
      multiplex test offered. CONCLUSIONS: These findings support theories suggesting
      that people use representative evaluations in attitude formation. The implication
      of these findings for further developments in genetic testing is that the
      communication and impact of multiplex testing may need to be considered in the
      light of a bias toward peak attitudes.

PMID- 23128583
TI  - A mixture distribution of spatial attention.
AB  - Although it may seem paradoxical, the unified-focus and multiple-foci theories of
      spatial selective attention are both well supported by experimental evidence.
      However, the apparent contradiction is illusory and the two competing views may
      be reconciled by a closer examination of the spatial mechanisms involved. We
      propose that the deployment of attention may be modeled as a mixture of
      individual distributions of attention and we tested this hypothesis in two
      experiments. Participants had to identify targets among distractors, with the
      targets presented at various distances from the cued locations. Experiment 1
      confirmed that the distribution of attention may be described by a mixture of
      individual distributions, each centered at a cued location. Experiment 2 showed
      that cue separation is an important determinant of whether spatial attention is
      divided or not.

PMID- 23128584
TI  - Individual differences in mental rotation: piecemeal versus holistic processing.
AB  - Two experiments tested the hypothesis that imagery ability and figural complexity
      interact to affect the choice of mental rotation strategies. Participants
      performed the <citationReference id="cr19-1" rid="c19">Shepard and Metzler
      (1971)</citationReference> mental rotation task. On half of the trials, the 3-D
      figures were manipulated to create "fragmented" figures, with some cubes missing.
      Good imagers were less accurate and had longer response times on fragmented
      figures than on complete figures. Poor imagers performed similarly on fragmented
      and complete figures. These results suggest that good imagers use holistic mental
      rotation strategies by default, but switch to alternative strategies depending on
      task demands, whereas poor imagers are less flexible and use piecemeal strategies
      regardless of the task demands.

PMID- 23128585
TI  - Conflict-specific effects of accessory stimuli on cognitive control in the Stroop
      task and the Simon task.
AB  - Both the Stroop and the Simon paradigms are often used in research on cognitive
      control, however, there is evidence that dissociable control processes are
      involved in these tasks: While conflicts in the Stroop task may be resolved
      mainly by enhanced task-relevant stimulus processing, conflicts in the Simon task
      may be resolved rather by suppressing the influence of task-irrelevant
      information on response selection. In the present study, we show that these
      control mechanisms interact in different ways with the presentation of accessory
      stimuli. Accessory stimuli do not affect cognitive control in the Simon task, but
      they impair the efficiency of cross-trial control processes in the Stroop task.
      Our findings underline the importance of differentiating between different types
      of conflicts and mechanisms of cognitive control.

PMID- 23128586
TI  - The European database for subspecialist training in neonatology - transparency
      achieved.
AB  - BACKGROUND: The European Society for Neonatology (ESN) developed a curriculum for
      subspecialist training in Europe recommending standards for national neonatal
      training programmes. We speculate whether these official recommendations are
      widely accepted or used in practice. OBJECTIVES: To characterize the variation in
      national neonatal training programmes, to enhance transparency, and to compare
      them to the ESN Curriculum. METHODS: We constructed a database based on the
      backbone of the ESN Curriculum: (1) training - knowledge, (2) training - skills,
      (3) key competencies, (4) personal development, and (5) recording of progress.
      National neonatal representatives from all 30 member states of the Union of
      European Medical Specialties (UEMS) provided data on national training
      programmes. RESULTS: Although only one country (3%) based its neonatology
      training entirely on the ESN Curriculum, we found high levels of uniformity among
      the UEMS member countries regarding knowledge, skills, and key competencies
      needed to practice neonatology at a tertiary care level. Discrepancy was
      encountered on ethical and legal issues and on personal development of the
      trainees. Mentoring and professional evaluation was generally not implemented in
      the participating countries. CONCLUSIONS: There is an awareness and readiness to
      focus on educational demands for neonatal trainees. Further discussions about the
      overall educational goals of neonatal training and the essence of practicing
      neonatology in each country are needed. The ESN will undertake this process to
      provide an updated and effective syllabus aimed to harmonize care and outcomes
      for babies and their families across Europe.

PMID- 23128587
TI  - Pediatric Critical Care Medicine reaches another milestone. Foreword.

PMID- 23128588
TI  - 2009 H1N1 pandemic: still questions to answer!*.

PMID- 23128589
TI  - You must walk before you can run*.

PMID- 23128590
TI  - An after action report of drotrecogin alpha (activated) and lessons for the
      future*.

PMID- 23128591
TI  - Central venous catheter complications: making headway*.

PMID- 23128592
TI  - Dexmedetomidine: should it be standard after pediatric cardiac surgery?*.

PMID- 23128593
TI  - Is it the neutrophil gelatinase-associated lipocalin or the pediatricRIFLE?*.

PMID- 23128594
TI  - Incubator noise: don't throw out the baby with the bathwater*.

PMID- 23128595
TI  - Heated, humidified high-flow nasal cannula therapy in viral bronchiolitis-
      Panacea, passing phase, or progress?*.

PMID- 23128596
TI  - New tricks for an old dog: multimodal neuromonitoring for diabetic ketoacidosis
      associated cerebral edema*.

PMID- 23128597
TI  - Ultrasonographic assessment of nail in psoriatic disease shows a link between
      onychopathy and distal interphalangeal joint extensor tendon enthesopathy.
AB  - OBJECTIVE: We compared ultrasonography (US) with the modified nail psoriasis
      severity index (mNAPSI) to investigate the nail plate, nail matrix and adjacent
      tendons in subjects with psoriatic nail disease and to test the hypothesis that
      nail involvement was specifically linked to extensor tendon enthesopathy.
      METHODS: 86 psoriatic patients (169 nails) and 20 healthy controls (HC) (40
      nails) were assessed with both the mNAPSI and US. The thickness of the nail
      plate, nail matrix region and adjacent extensor tendon were assessed and compared
      with physical examination findings. RESULTS: A good agreement between clinical
      and sonographic nail findings was noted (kappa value = 0.52, p < 0.0001).
      Entheseal thickening of the extensor tendon on US was more frequent in patients
      with clinical nail disease compared to patients without clinical nail disease in
      both psoriasis and psoriatic arthritis (38 vs. 16%, p = 0.03, and 47 vs. 19%, p =
      0.008, respectively). Nail thickness, nail matrix and adjacent skin thickness
      were higher in psoriatic patients compared to HC. CONCLUSION: US and clinical
      findings show good correlation for the assessment of the nail in psoriatic
      disease. The demonstration of extensor tendon enthesopathy in both psoriasis and
      psoriatic arthritis supports the importance of enthesopathy in nail disease
      pathogenesis whether or not clinical arthritis is present.

PMID- 23128598
TI  - Bufalin prevents the migration and invasion of T24 bladder carcinoma cells
      through the inactivation of matrix metalloproteinases and modulation of tight
      junctions.
AB  - Bufalin, a cardiotonic steroid extracted from toad venom, has generally been
      known to possess a range of biological activities; however, only a few studies
      have reported the anti-metastatic activity of bufalin. In the present study, we
      investigated the inhibitory effects of bufalin on cell migration and invasion,
      two critical cellular processes that are often deregulated during metastasis,
      using the human bladder cancer cell line, T24. Within the concentration range
      that was not cytotoxic, bufalin markedly inhibited the cell motility and
      invasiveness of T24 cells. The inhibitory effects of bufalin on cell invasiveness
      were associated with the tightening of tight junctions (TJs), which was
      demonstrated by an increase in transepithelial electrical resistance (TER).
      Bufalin treatment also repressed the levels of claudin proteins (claudin-2, -3
      and -4) and the major components of TJs that play key roles in the control and
      selectivity of paracellular transport. Furthermore, the activities of matrix
      metalloproteinase (MMP)-2 and -9 in T24 cells were dose-dependently inhibited by
      treatment with bufalin and this also correlated with a decrease in their mRNA and
      protein expression levels; however, the mRNA and protein levels of the tissue
      inhibitor of metalloproteinase (TIMP)-1 and -2 were increased. In addition, these
      effects were related to the increased phosphorylation of the extracellular signal
      regulated protein kinase (ERK) pathway. The inhibition of ERK (PD98059)
      significantly prevented the bufalin-induced suppression of T24 cell migration.
      These findings suggest that bufalin inhibits the migration and invasion of T24
      cells by modulating the activity of TJs and MMPs, possibly in association with
      the activation of ERK.

PMID- 23128599
TI  - Red blood cell distribution width in 'non-dippers' versus 'dippers'.
AB  - OBJECTIVES: Because both high red cell distribution width (RDW) and non-dipping
      hypertension are closely related to adverse cardiovascular outcomes and higher
      inflammatory status, we aimed to investigate whether there is any relationship
      between RDW and dipping/non-dipping hypertension status. METHODS: The present
      study involved 123 hypertensive patients and 65 age- and gender-matched healthy,
      normotensive subjects. Hypertensive patients were divided into two groups: 56
      dipper patients (20 males, mean age 51.9 +/- 15.3 years) and 67 non-dipper
      patients (27 males, mean age 55.6 +/- 15.0 years). If the systolic daytime blood
      pressure (BP) of the patients decreased by at least 10% during the nighttime,
      these subjects were 'dippers', and all other subjects were 'non-dippers'.
      RESULTS: Both dipper patients and non-dipper patients had higher levels of RDW
      compared to normotensives (13.5 +/- 0.89 and 14.1 +/- 1.33 vs. 13.0 +/- 1.42%, p
      = 0.027 and p < 0.001, respectively). Also RDW values in non-dippers were
      statistically higher compared to those in dippers (p = 0.008). Although there
      were negative correlations between RDW values and nocturnal systolic BP fall (p =
      0.027, r = -0.199) and diastolic BP fall (p = 0.383, r = -0.079) in all
      hypertensive patients, these correlations did not reach a statistically
      significant level. CONCLUSION: Our study demonstrates that non-dippers have high
      RDW levels compared to both dippers and controls.

PMID- 23128601
TI  - Interactions of oxaliplatin with the cytoplasmic thiol containing ligand
      glutathione.
AB  - The complexation of the Pt-based anti-cancer drug oxaliplatin (OxPt) with
      biological ligands other than DNA is believed to be a major cellular sink for the
      drug reducing its therapeutic effect and acting as a potential cause of toxicity.
      In this paper, linear ion trap electrospray ionization mass spectrometry was
      employed to study the interaction of oxaliplatin with the cytoplasmic thiol
      containing tripeptide ligand gamma-l-glutamyl-l-cysteinyl-glycine (GSH) this
      being the most abundant low-molecular-weight thiol containing molecule in human
      cells. Evidence of protonated dimers and multimers of oxaliplatin, protonated
      multimers of glutathione as well as several different combinations of these
      protonated species is presented. Most species observed were unambiguously
      assigned and compared to their theoretical isotopic patterns. Fragmentation of
      the collisionally-activated protonated complex of glutathione with oxaliplatin
      [GSH + OxPt + H](+) resulted in the formation of several species. No experimental
      evidence for [GSH + H](+) formation from the [OxPt + GSH + H](+) precursor was
      observed. Density functional calculations at B3LYP/LANL2DZ were used to obtain
      structural information and relative free energies of different isomers of the
      observed precursor [OxPt + GSH + H](+) both in the gas phase and in solution as
      well as to probe its fragmentation, highlighting mechanisms that account for all
      the experimental results. Data are presented to show several binding modes
      between electron rich sites such as S, N, O centers of GSH and the Pt metal of
      oxaliplatin. Calculations were also employed to obtain proton affinities and free
      energies of key reactions. The proton affinities of GSH and OxPt at 298 K were
      calculated to be 255.3 and 233.5 kcal mol(-1) respectively. The enthalpy and free
      energy, based on the most thermodynamically favored conformers of the reactants
      and products, for the addition reaction [Pt(dach)](2+) + [GSH - H](-)    -> [GSH 
      H + Pt(dach)](+) (where dach represents diaminocyclohexane) in the gas phase at
      298 K were determined to be -311.3 and -290.2 kcal mol(-1) respectively.
      Similarly, the enthalpy of the gas phase reaction [Pt(dach)](2+) + GSH -> [GSH +
      Pt(dach)](2+) at 298 K was determined to be -169.2 kcal mol(-1).

PMID- 23128603
TI  - Scarecrow plays a role in establishing Kranz anatomy in maize leaves.
AB  - More than a quarter of the primary productivity on land, and a large fraction of
      the food that humans consume, is contributed by plants that fix atmospheric CO(2)
      by C(4) photosynthesis. It has been estimated that transferring the C(4) pathway
      to C(3) crops could boost yield by 50% and also increase water use efficiency and
      reduce the need for fertilizer, particularly in dry, hot environments. The high
      productivity of maize (Zea mays), sugarcane (Saccharum spp.) and several emerging
      bioenergy grasses is due largely to C(4) photosynthesis, which is enabled by the
      orderly arrangement, in concentric rings, of specialized bundle sheath and
      mesophyll cells in leaves in a pattern known as Kranz anatomy. Here we show that
      PIN, the auxin efflux protein, is present in the end walls of maize bundle sheath
      cells, as it is in the endodermis of the root. Since this marker suggests the
      expression of endodermal genetic programs in bundle sheath cells, we determined
      whether the transcription factor SCARECROW, which regulates structural
      differentiation of the root endodermis, also plays a role in the development of
      Kranz anatomy in maize. Mutations in the Scarecrow gene result in proliferation
      of bundle sheath cells, abnormal differentiation of bundle sheath chloroplasts,
      vein disorientation, loss of minor veins and reduction of vein density. Further
      characterization of this signal transduction pathway should facilitate the
      transfer of the C(4) trait into C(3) crop species, including rice.

PMID- 23128602
TI  - Circadian clock regulates dynamic chromatin modifications associated with
      Arabidopsis CCA1/LHY and TOC1 transcriptional rhythms.
AB  - Circadian clocks enable organisms to adapt to a 24 h diurnal cycle and anticipate
      rhythmic changes in the environment. The Arabidopsis central oscillator contains
      three genes encoding core clock components. CIRCADIAN CLOCK ASSOCIATED 1
      (CCA1)/LATE ELONGATED HYPOCOTYL (LHY) and TIMING OF CAB EXPRESSION 1 (TOC1)
      reciprocally repress genes encoding each other and are critical for the
      generation of circadian rhythms controlling many clock outputs. A precise
      regulation of transcriptional events is, therefore, essential for proper
      circadian function. Here, we investigated histone 3 (H3) tail modifications of
      CCA1, LHY and TOC1 under various conditions. We found specific association of
      only H3K4Me3 and H3K9/14Ac with the translational start site of these three
      genes. These H3 marks were enriched at circadian time points of their increased
      transcription at different photoperiods and under free-running conditions,
      suggesting circadian regulation of H3 modifications. Analysis of clock
      compromised CCA1-overexpressing lines provided evidence that light/dark
      photoperiods signal the establishment of these chromatin changes which are gated
      by the clock.

PMID- 23128604
TI  - Electrospun biomimetic scaffold of hydroxyapatite/chitosan supports enhanced
      osteogenic differentiation of mMSCs.
AB  - Engaging functional biomaterial scaffolds to regulate stem cell differentiation
      has drawn a great deal of attention in the tissue engineering and regenerative
      medicine community. In this study, biomimetic composite nanofibrous scaffolds of
      hydroxyapatite/chitosan (HAp/CTS) were prepared to investigate their capacity for
      inducing murine mesenchymal stem cells (mMSCs) to differentiate into the
      osteogenic lineage, in the absence and presence of an osteogenic supplementation
      (i.e., ascorbic acid, beta-glycerol phosphate, and dexamethasone), respectively.
      Using electrospun chitosan (CTS) nanofibrous scaffolds as the control, cell
      morphology, growth, specific osteogenic genes expression, and quantified proteins
      secretion on the HAp/CTS scaffolds were sequentially examined and assessed. It
      appeared that the HAp/CTS scaffolds supported better attachment and proliferation
      of the mMSCs. Most noteworthy was that in the absence of the osteogenic
      supplementation, expression of osteogenic genes including collagen I (Col I),
      runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), and
      osteocalcin (OCN) were significantly upregulated in mMSCs cultured on the HAp/CTS
      nanofibrous scaffolds. Also increased secretion of the osteogenesis protein
      markers of alkaline phosphatase and collagen confirmed that the HAp/CTS
      nanofibrous scaffold markedly promoted the osteogenic commitment in the mMSCs.
      Moreover, the presence of osteogenic supplementation proved an enhanced efficacy
      of mMSC osteogenesis on the HAp/CTS nanofibrous scaffolds. Collectively, this
      study demonstrated that the biomimetic nanofibrous HAp/CTS scaffolds could
      support and enhance the adhesion, proliferation, and particularly osteogenic
      differentiation of the mMSCs. It also substantiated the potential of using
      biomimetic nanofibrous scaffolds of HAp/CTS for functional bone repair and
      regeneration applications.

PMID- 23128605
TI  - Suppression of FUT1 attenuates cell proliferation in the HER2-overexpressing
      cancer cell line NCI-N87.
AB  - Lewis Y (LeY) antigen is an oligosaccharide that is highly expressed at the cell
      surface in various human cancers. Increased LeY expression activates epidermal
      growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2)
      and promotes cell proliferation in EGFR-overexpressing cells. However, the effect
      of downregulation of LeY expression on cell proliferation in HER2-overexpressing
      cells remains unknown. FUT1 encodes alpha1,2-fucosyltransferase, a key enzyme for
      LeY synthesis. We knocked down FUT1 by short interfering RNA (siRNA) in four HER2
      overexpressing human cancer cell lines, including NCI-N87, MKN7, SKBr3 and BT474.
      We investigated whether downregulation of LeY and alteration in the glycosylation
      status of these cells affect cell proliferation and HER2 activation. Knocking
      down FUT1 expression markedly inhibited proliferation of NCI-N87, which highly
      expressed EGFR and was sensitive to EGFR deprivation. Furthermore, FUT1 siRNA
      downregulated the total amount of HER2 protein, phosphorylation of HER2 and EGFR,
      and phosphorylation of extracellular signal-regulated kinase (ERK) in this cell
      line. Moreover, the marked downregulation of phosphorylation of HER2 and ERK was
      observed following short-time EGF-stimulation. These effects were not observed in
      the other three cell lines. Our results suggest that knockdown of FUT1
      downregulates HER2 signaling via EGFR downregulation. FUT1 may serve as a new
      molecular target for HER2-overexpressing human cancers with activated EGFR
      signaling.

PMID- 23128606
TI  - Serum brain-derived neurotrophic factor and nerve growth factor concentrations
      change after alcohol withdrawal: preliminary data of a case-control comparison.
AB  - BACKGROUND: Brain-derived neurotrophic factor (BDNF) and nerve growth factor
      (NGF) are involved in neuroadaptation and foster survival of central and
      peripheral neurons. In this study, we addressed the question whether BDNF and NGF
      serum concentrations change during subacute alcohol withdrawal in patients with
      alcohol dependence compared to healthy controls. METHODS: Fifteen patients (age
      48.6 +/- 7 years) and 15 healthy age-matched controls (age 48.8 +/- 7 years)
      participated consecutively in a 2-week withdrawal study. RESULTS: Mean BDNF
      levels (7.8 ng/ml, IQR = 4.4-10.7 vs. 16.5 ng/ml, IQR = 13.9-25.6; Z = -3.8, p <
      0.0001) and NGF levels (5.8 pg/ml, IQR = 3.8-13.0 vs. 18.4 pg/ml, IQR = 10.9
      25.1; Z = -2.5, p = 0.012) were significantly decreased in alcohol-dependent
      subjects when compared to healthy matched controls. NGF concentrations decreased
      significantly from day 3 to day 14 (Z = -2.36; p = 0.019). Mean BDNF
      concentrations showed a tendency to increase after withdrawal from day 3 to day
      14 (Z = 1.7; p = 0.078). CONCLUSION: Decreased NGF and BDNF concentrations in
      patients suffering from alcohol dependence, which stabilize after physical
      withdrawal, are in line with withdrawal symptoms and neurological risk factors.
      In turn, increase of BDNF after acute withdrawal might be connected to
      neurobiological and behavioral stabilization.

PMID- 23128607
TI  - Treadmill and wheel exercise alleviate lipopolysaccharide-induced short-term
      memory impairment by enhancing neuronal maturation in rats.
AB  - Lipopolysaccharide (LPS) is an endotoxin derived from Gram-negative bacteria,
      which induces brain inflammation. LPS-induced brain inflammation deteriorates
      hippocampus-dependent cognitive deficits. In the present study, we investigated
      the effects of forced treadmill exercise and voluntary wheel exercise on short
      term memory in relation to neuronal maturation in LPS-induced brain inflammation
      of rats. Brain inflammation in rats was induced by an injection of LPS into the
      cerebral ventricle. Short-term memory was evaluated using a step-down avoidance
      task. Cell proliferation in the hippocampal dentate gyrus was determined by 5
      bromo-2'-deoxyuridine (BrdU), a marker of new cells, immunohistochemistry.
      Western blot analysis for the determination of doublecortin (DCX), a marker of
      immature neurons and neuronal nuclear antigen (NeuN), a marker of mature neurons,
      was performed. In the present study, LPS-induced brain inflammation impaired
      short-term memory by increasing DCX expression and suppressing NeuN expression.
      These results suggest that LPS-induced brain inflammation disturbs neuronal
      maturation. The number of BrdU-positive cells in the hippocampal dentate gyrus
      was increased by LPS injection. This increase in the number of BrdU-positive
      cells can be ascribed to the increase in the number of of immature neurons
      following LPS injection. On the other hand, forced treadmill exercise and
      voluntary wheel exercise improved brain inflammation-induced short-term memory
      impairment by suppressing DCX expression and increasing NeuN expression,
      enhancing neuronal maturation. Forced treadmill exercise and voluntary wheel
      exercise showed similar efficacy. From these results, it can be inferred that
      forced treadmill exercise and voluntary wheel exercise may improve memory
      function deteriorated by brain inflammation. 

PMID- 23128608
TI  - [Ethics, health and health care in prison].

PMID- 23128609
TI  - [The SciELO indexation: a new stage for the Revista Espanola de Sanidad
      Penitenciaria].

PMID- 23128610
TI  - [A quality improvement program for mental health care in prison: An evaluation of
      the results (2000-2005)].
AB  - INTRODUCTION: We describe the results of a program to improve the quality of
      mental health care amongst inmates after six years (2000-2005). MATERIALS AND
      METHODS: We designed a series of studies lasting one to two years and used them
      as a basis for the program. In 2000 we studied demand for primary health care in
      the treatment of mental health problems in the prison health centre. In 2001
      compulsive demand for psychotropic medication was studied. In 2002 the existence
      of mental disorders in a random sample of 60 inmates. In 2003 and 2004 we studied
      the relationship between mental disorder and adjustment problems, first by
      relating sanctions for aggressive behaviour with mental disorders using a random
      sample of 60 inmates and then relating inappropriate adjustment behaviours with
      use of psychotropic medication in a random sample of 520 inmates. In 2005 we
      studied the functioning of the prison health care centre as a resource in the
      treatment of inmates with severe mental illness by taking data from admissions
      over a seven month time period. RESULTS: 50% of the primary health care
      consultations were related in one or another with a mental health problem. 59% of
      the inmates showed symptoms of some type of mental disorder, 56.6% of those being
      addictive disorders while the other 30% were Personality Disorders. 20% of the
      inmates required referral to the consultant psychiatrist, the most common cause
      of referral being inappropriate or maladjusted behaviour (46%) and the most
      common diagnosis Depressive Disorder associated with Addictive Disorder
      (psychoactive substances). We could see a correlation between the number of
      sanctions for aggressive conduct and the diagnosis of Personality Disorder. A
      similar correlation could be seen between adjustment problems marked on an
      objective scale and the use of psychotropic medication. 50% of the inmates in the
      health centre sick bay were there because of mental disorder, and 43% had been
      admitted directly after sentencing. DISCUSSION: A limitation of this study is
      that it only goes as far as describing a set of findings about the quality of
      mental health care and does not propose any relevant improvements. This work
      shall be left for later studies. There is clearly a great need for mental health
      care amongst prisoners. Pathologies that cause inappropriate behaviour, most
      commonly understood as the expression of inadequate interpersonal relationships,
      are the most common disorders and are generally associated with psychoactive
      substance abuse. The model we propose is that of the consultant psychiatrist
      working in close cooperation with the primary health care team as the best answer
      to this type of health care need. Health care centres are not sufficiently
      equipped to respond to the situation and have no other option but to accept
      patients who have usually committed some type of violent crime and who have not
      been admitted to specialised centres outside prison, usually because adequate
      security measures are lacking.

PMID- 23128611
TI  - [Study of the use of atypical antipsychotic drugs in Malaga Prison].
AB  - AIM: we studied the use of psychotropic drugs belonging to the group of atypical
      neuroleptics in Malaga State Prison (Centro Penitenciario de Malaga) from 2003 to
      2004. We also compared the results of this study with references taken from the
      Primary Health Care District of Guadalhorce. MATERIALS AND METHODS: A
      retrospective study was carried out on the use of antipsychotic drugs from 2003
      to 2004 in Malaga State Prison. A comparison was then made with the use of this
      type of medication in the Primary Health Care District of Guadalhorce. Data on
      medication consumption was taken from medical orders received at the prison
      during this study. The ATC (Anatomical Therapeutic and Chemical Classifying
      System) was used for classifying the active principles. The prison's own data
      base (SANIT) was used for calculating the number of containers. For calculating
      the DDD, the ratio DDD/1000 inmates/day was utilised. RESULTS: The use of
      atypical antipsychotic medication in the prison increased. There is an increasing
      trend towards the use of quetiapine in small doses. The use of risperidone went
      down during the period of this study, although it is still the most commonly used
      drug in DDD and in consumed containers. The Primary Health care results indicate
      a trend in the opposite direction. CONCLUSION: The use of the group of drugs in
      this study has decreased in the Primary Health Care area, possibly because of
      special medical control measures such as the control stamp. In Malaga Prison use
      of these drugs has increased. The reasons for this difference are as yet unknown.

PMID- 23128612
TI  - [Expert recommendations for the diagnosis and treatment of chronic hepatitis C
      infection in the prison setting].
AB  - The prevalence of HCV infection in Spanish prisons is very high (38.5%). The
      characteristics of the infected patients, particularly the high rate of HIV
      coinfection, makes it very likely that the morbidity and mortality produced by
      serious liver disease secondary to this infection will increase considerably in
      the coming years. A group of Spanish experts with experience in patients who are
      inmates has been invited to establish a series of recommendations for the
      diagnosis and treatment of chronic hepatitis C infection in Spanish prisons.

PMID- 23128613
TI  - [Tatuajes alusivos al consumo de drogas].

PMID- 23128614
TI  - Journey to eliminating health care disparities: the urgency of affirming values
      within our patients, profession, health care system, and society.

PMID- 23128615
TI  - Modelling micro-pollutant fate in wastewater collection and treatment systems:
      status and challenges.
AB  - This paper provides a comprehensive summary on modelling of micro-pollutants'
      (MPs) fate and transport in wastewater. It indicates the motivations of MP
      modelling and summarises and illustrates the current status. Finally, some
      recommendations are provided to improve and diffuse the use of such models. In
      brief, we conclude that, in order to predict the contaminant removal in
      centralised treatment works, considering the dramatic improvement in monitoring
      and detecting MPs in wastewater, more mechanistic approaches should be used to
      complement conventional, heuristic and other fate models. This is crucial, as
      regional risk assessments and model-based evaluations of pollution discharge from
      urban areas can potentially be used by decision makers to evaluate effluent
      quality regulation, and assess upgrading requirements, in the future.

PMID- 23128616
TI  - Pilot-scale demonstration of the hybrid zero-valent iron process for treating
      flue-gas-desulfurization wastewater: part I.
AB  - The hybrid zero-valent-iron (hZVI) process is a novel chemical treatment process
      that has shown great potential in previous laboratory and field bench-top scale
      tests for removing selenium, mercury and nutrients from various industrial
      wastewaters. In this study, a pilot-scale demonstration was conducted to
      continuously treat 3.8-7.6 L/min (1-2 gpm) of the flue-gas-desulfurization (FGD)
      wastewater at a coal-fired power plant for five months. Results show that the
      hZVI process could simultaneously reduce selenate-Se from 1 to 3 mg/L to below 10
      MUg/L and mercury from over 100 MUg/L to below 10 ng/L in compliance with the new
      stringent effluent discharge limits planned by the U.S. EPA for Se and Hg. A
      three-stage hZVI system with a combined hydraulic retention time of 12 h is
      sufficient for Se treatment, while a single-stage system can meet Hg treatment
      requirement. The successful pilot study demonstrated that the hZVI process is
      scalable and could be a reliable, low-cost, high-performance treatment platform
      with many application potentials, particularly, for solving some of the toughest
      heavy metal water problems.

PMID- 23128617
TI  - Mathematical modeling of upflow anaerobic sludge blanket (UASB) reactor treating
      domestic wastewater.
AB  - Although the upflow anaerobic sludge blanket (UASB) reactor has been widely
      applied for domestic wastewater treatment in many developing countries, there is
      no sufficient mathematical model for proper design and operation of the reactor.
      An empirical model based on non-linear regression was developed to represent the
      physical and chemical removal of suspended solids (SS) in the reactor. Moreover,
      a simplified dynamic model based on ADM1 and the empirical model for SS removal
      was developed for anaerobic digestion of the entrapped SS and dissolved matter in
      the wastewater. The empirical model showed that effluent suspended chemical
      oxygen demand (COD(ss)) concentration is directly proportional to the influent
      COD(ss) concentration and inversely proportional to both the hydraulic retention
      time (HRT) of the reactor and wastewater temperature. For obtaining sufficient
      COD(ss) removal, the HRT of the UASB reactor must be higher than 4 h, and higher
      HRT than 12 h slightly improved COD(ss) removal. The dynamic model results showed
      that the required time for filling the reactor with sludge mainly depends on
      influent total chemical oxygen demand (COD(t)) concentration and HRT. The
      influent COD(t) concentration, HRT and temperature play a crucial role on the
      performance of the reactor. The results indicated that shorter HRT is needed for
      optimization of COD(t) removal, as compared with optimization of COD(t)
      conversion to methane. Based on the model results, the design HRT of the UASB
      reactor should be selected based on the optimization of wastewater conversion and
      minimization of biodegradable SS accumulation in the sludge bed, not only based
      on COD removal, to guarantee a stable reactor performance.

PMID- 23128618
TI  - Risk and monitoring based indicators of receiving water status: alternative or
      complementary elements in IWRM?
AB  - The European Water Framework Directive (WFD) was enacted in the year 2000 with a
      stepwise approach. After legal implementation in the various member states large
      efforts were undertaken for the initial characterization of water bodies, risk
      assessment, to implement extensive monitoring schemes and to develop management
      plans at different aggregation levels by the year 2010. The initial
      characterization process and risk assessment had to be finalized by 2004 and
      delineated water bodies including a typological classification and identified the
      significant pressures and impacts in a screening procedure. In parallel,
      monitoring programmes and new biological indicator systems were developed in
      order to proof and refine the results of the risk assessment with an ecological
      indicator based assessment in a subsequent step which was finalized in 2009.
      Although the risk assessment for Germany was based on existing data that were
      originally collected for other purposes and came from a large variety of
      environmental or economical sectors, the results differ only slightly from the
      monitoring and indicator based information with respect to classifications of the
      'ecological status' and 'chemical status'. From this result we conclude that a
      risk assessment based on a careful application and intelligent combination of
      existing data sources with proven quality allows the recognition of trends and
      the identification of priorities for action of measures already at an early stage
      of a management process. However, monitoring schemes and advanced sets of
      ecological indicators are essential in later management steps both for narrowing
      uncertainties remaining from the risk assessment and to allow for effect controls
      of implemented measures. Moreover, these monitoring indicators should
      differentiate the effects of multiple stressors more factor specific and with
      respect to ecosystem states and functions. In conclusion, we see risk and
      indicator based assessments as complementary elements in Integrated Water
      Resources Management (IWRM), which have to be linked in systematic and phased
      procedures.

PMID- 23128619
TI  - Sizing mitigation wetlands in agricultural watersheds.
AB  - In this study, we investigated use of microcosms to supplement field studies for
      establishing the size of wetlands required to mitigate nitrate pollution in
      agricultural watersheds. Wetlands investigated in this study were located in San
      Joaquin Valley (California, USA) and demonstrated mean nitrate-nitrogen mass
      removal efficiencies ranging between 10 and 34%. Mean areal nitrate removal rates
      (J) ranged from 142 to 380 mg-N m(-2) d(-1). First-order rate constants
      determined from field data had a high variance, with confidence intervals greater
      than 57% of mean values. Sediments and rooted plants from one site were placed in
      a flow-through microcosm and measurements of nitrate removal kinetics were made
      and compared with field results. The apparent half-saturation constant (K(m)) and
      maximum removal rate (J(max)) for nitrate-nitrogen were 43.8 mg/L and 4.11 g m(
      2) d(-1) in the microcosm. The first-order rate constant from the microcosm (10.4
      cm d(-1)) was in close agreement with the value for the field site (11.9 cm d(
      1)) and had a confidence interval of less than 16%. Using this improved first
      order rate constant, it was determined that between 1.3 and 3.6% of the land in
      the watershed should be managed as mitigation wetland, with the area required
      dependent on the level of nitrate reduction desired and how closely the wetland
      design approximates plug-flow.

PMID- 23128620
TI  - Trends and variability of climate and river flow in the region of Costa das
      Baleias, Brazil.
AB  - There is an ongoing effort by the scientific community to regionalize climate
      studies to support local development plans. The area of interest is the Costa das
      Baleias on the east coast of northeast Brazil. It is located in a transition
      region of precipitation trends, and so assessing the local signal and magnitude
      is necessary. A series of annual anomalies of surface air temperature,
      precipitation and river discharge were analyzed from 1946 to 2010. The modified
      Mann-Kendall test was applied to detect trends. Temperature anomalies showed a
      consistent positive trend since 1950. Precipitation anomalies tended to decrease,
      though not significantly. River discharge rates showed a consistent positive
      trend. However, from the 1980s onwards, both the precipitation and the river
      discharge anomalies had the same decreasing tendency. The precipitation and
      discharge behavior are likely due to the combined effect of human interventions
      in the river basins including local, synoptic and global climate effects. The
      inter-annual variability was characterized by spectral analysis. Cycles were
      identified for the precipitation and the river discharge with periods of 2-3
      years, 3-4 years, 7-8 years and 11-12 years. The decadal frequency is consistent
      with the South Atlantic and El Nino indices. This work strongly indicates that
      climate is changing in Costa das Baleias and further work is needed to
      investigate the mechanisms that link local to large-scale variability.

PMID- 23128621
TI  - Design and assessment of urban drainage and water reuse systems for the
      reconstruction of formerly industrial areas: a case in Beijing.
AB  - The Shougang Group is an industrial steel enterprise occupying 800 ha in Beijing
      that will cease production by 2010. The area will be converted to a new financial
      and commercial zone. The rebuilding of the water infrastructure in this area
      should address water shortages in Beijing and retain the industrial landmark of a
      large cooling water tank. A design framework and an assessment system with 11
      indicators were developed for this purpose. Four reconstruction schemes are
      presented here. Scheme 1 is a traditional system that completely depends on
      outside the municipal facility. Schemes 2, 3, and 4 are systems to separately
      discharge greywater and blackwater. Scheme 4 uses a vacuum system that allows the
      reclamation of nutrients. Schemes 2 and 4 use wetland-treated greywater to fill
      the water tank. Scheme 3 reuses greywater for toilets after on-site treatment.
      Scheme 2 is recommended due to its lower cost, greater environmental benefit,
      moderate resource reclamation, and higher technical feasibility.

PMID- 23128622
TI  - Identifying energy and carbon footprint optimization potentials of a sludge
      treatment line with Life Cycle Assessment.
AB  - This study exemplifies the use of Life Cycle Assessment (LCA) as a tool to
      quantify the environmental impacts of processes for wastewater treatment. In a
      case study, the sludge treatment line of a large wastewater treatment plant
      (WWTP) is analysed in terms of cumulative energy demand and the emission of
      greenhouse gases (carbon footprint). Sludge treatment consists of anaerobic
      digestion, dewatering, drying, and disposal of stabilized sludge in mono- or co
      incineration in power plants or cement kilns. All relevant forms of energy demand
      (electricity, heat, chemicals, fossil fuels, transport) and greenhouse gas
      emissions (fossil CO(2), CH(4), N(2)O) are accounted in the assessment, including
      the treatment of return liquor from dewatering in the WWTP. Results show that the
      existing process is positive in energy balance (-162 MJ/PE(COD) * a) and carbon
      footprint (-11.6 kg CO(2)-eq/PE(COD) * a) by supplying secondary products such as
      electricity from biogas production or mono-incineration and substituting fossil
      fuels in co-incineration. However, disposal routes for stabilized sludge differ
      considerably in their energy and greenhouse gas profiles. In total, LCA proves to
      be a suitable tool to support future investment decisions with information of
      environmental relevance on the impact of wastewater treatment, but also urban
      water systems in general.

PMID- 23128623
TI  - Application of response surface method to carbamazepine removal in photo
      ozonation reaction under alkaline condition.
AB  - In this study, the photo-ozonation reaction for carbamazepine (CBZ) removal was
      investigated under alkaline conditions. Response surface methodology based on a
      central composite design was used to obtain the optimum experimental conditions,
      and examine both main and interaction effects of the photo-ozonation reaction
      variables such as O(3) concentration, H(2)O(2) concentration and UV intensity.
      The level of O(3) concentration significantly influenced CBZ removal (p < 0.001).
      CBZ removal increased with increasing both O(3) and H(2)O(2) concentration up to
      a certain level, whereas further increase in O(3) and H(2)O(2) concentration
      resulted in an adverse effect due to the hydroxyl radical scavenging effect. The
      optimum conditions for complete CBZ removal at pH 9 were found to be 0.89 mg of
      O(3) l(-1), 4.85 mg of H(2)O(2) l(-1) and 3.18 mW of UV intensity cm(-2),
      respectively.

PMID- 23128624
TI  - Car wash wastewater treatment and water reuse - a case study.
AB  - Recent features of a car wash wastewater reclamation system and results from a
      full-scale car wash wastewater treatment and recycling process are reported. This
      upcoming technology comprises a new flocculation-column flotation process, sand
      filtration, and a final chlorination. A water usage and savings audit (22 weeks)
      showed that almost 70% reclamation was possible, and fewer than 40 L of fresh
      water per wash were needed. Wastewater and reclaimed water were characterized by
      monitoring chemical, physicochemical and biological parameters. Results were
      discussed in terms of aesthetic quality (water clarification and odour), health
      (pathological) and chemical (corrosion and scaling) risks. A microbiological risk
      model was applied and the Escherichia coli proposed criterion for car wash
      reclaimed water is 200 CFU 100 mL(-1). It is believed that the discussions on car
      wash wastewater reclamation criteria may assist institutions to create laws in
      Brazil and elsewhere.

PMID- 23128625
TI  - Risk assessment of treated municipal wastewater reuse in Sicily.
AB  - In Italy, the restrictive approach for treated wastewater reuse in agriculture
      has led to some difficulties in promoting this practice. In order to assess the
      health risk associated with the use of wastewater in agriculture, an experiment
      was conducted in an open field near the constructed wetland (CW) system of San
      Michele di Ganzaria (Eastern Sicily), during the irrigation seasons 2004-2009. In
      particular the impact on tomato crops of drip and sub-drip irrigation with
      treated municipal wastewater, as well as effects of wastewater reuse on the
      irrigation system, main production features, hydrological soil behaviour, and
      microbial soil and products contamination were investigated. Notwithstanding the
      fact that globally CW effluents did not match microbiological standards for
      wastewater reuse of Italian legislation, the median infection risk (function of
      the recommended tolerable additional disease burden of 10(-6) DALY (disability
      adjusted life year) loss per person per year) suggested by the 2006 World Health
      Organization Guidelines for rotavirus, Campylobacter and Cryptosporidium for
      lettuce irrigation under unrestricted irrigation scenario was achieved.

PMID- 23128626
TI  - The management of urban surface water flood risks: SUDS performance in flood
      reduction from extreme events.
AB  - The need to improve the urban drainage network to meet recent urban growth and
      the redevelopment of old industrial and commercial areas provides an opportunity
      for managing urban surface water infrastructure in a more sustainable way. The
      use of sustainable urban drainage systems (SUDS) can reduce urban surface water
      flooding as well as the pollution impact of urban discharges on receiving waters.
      However, these techniques are not yet well known by many stakeholders involved in
      the decision-making process, or at least the evidence of their performance
      effectiveness may be doubted compared with more traditional engineering solutions
      often promoted by existing 1D/2D drainage models. The use of geographic
      information systems (GIS) in facilitating the inter-related risk analysis of
      sewer surface water overflows and urban flooding as well as in better
      communication with stakeholders is demonstrated in this paper. An innovative
      coupled 1D/2D urban sewer/overland flow model has been developed and tested in
      conjunction with a SUDS selection and location tool (SUDSLOC) to enable a robust
      management approach to surface water flood risks and to improve the resilience of
      the urban drainage infrastructure. The paper demonstrates the numerical and
      modelling basis of the integrated 1D/2D and SUDSLOC approach and the working
      assumptions and flexibility of the application together with some limitations and
      uncertainties. The role of the SUDSLOC modelling component in quantifying flow,
      and surcharge reduction benefits arising from the strategic selection and
      location of differing SUDS controls are also demonstrated for an extreme storm
      event scenario.

PMID- 23128627
TI  - Realising sustainable urban water management: can social theory help?
AB  - It has been acknowledged, in Australia and beyond, that existing urban water
      systems and management lead to unsustainable outcomes. Therefore, our current
      socio-technical systems, consisting of institutions, structures and rules, which
      guide traditional urban water practices, need to change. If a change towards
      sustainable urban water management (SUWM) practices is to occur, a transformation
      of our established social-technical configuration that shapes the behaviour and
      decision making of actors is needed. While some constructive innovations that
      support this transformation have occurred, most innovations remain of a technical
      nature. These innovative projects do not manage to achieve the widespread social
      and institutional change needed for further diffusion and uptake of SUWM
      practices. Social theory, and its research, is increasingly being recognised as
      important in responding to the challenges associated with evolving to a more
      sustainable form of urban water management. This paper integrates three areas of
      social theories around change in order to provide a conceptual framework that can
      assist with socio-technical system change. This framework can be utilised by
      urban water practitioners in the design of interventions to stimulate transitions
      towards SUWM.

PMID- 23128628
TI  - Antibiotic resistance among autochthonous aquatic environmental bacteria.
AB  - Antibiotics are widely used in both human and veterinary medicine and antibiotic
      resistant bacteria cause problems in antibiotic therapy. The current study was
      conducted in the catchment area of the river Swist (Germany) and focuses on the
      resistance of environmental Rhodospirillaceae to antibiotics used in human
      medicine. The samples collected reflect different levels of human impact on the
      environment. In total, 614 isolates were tested for antibiotic susceptibility.
      About half of these isolates were susceptible to all substances tested. Oxacillin
      resistance was observed most frequently (41%). Resistant Rhodospirillaceae were
      detected in wastewater effluent from a municipal sewage treatment plant, as well
      as in non-polluted upper reaches. The highest multi-resistance level was detected
      in small tributaries and it surprisingly decreased with an increasing influence
      of municipal wastewater. It could be shown that the detected resistances were
      acquired rather than intrinsic. Besides natural occurrence of multi-resistance
      among non-sulphur purple bacteria, horizontal gene transfer and acquired cross
      resistance against veterinary antibiotics are assumed to be important factors. To
      the authors' knowledge, this is the first study investigating the potential of
      Rhodospirillaceae as a reservoir for resistance to antibiotics used in human
      medicine. The consequence for resistance prevalence in human pathogens and for
      their antibiotic therapy needs evaluation.

PMID- 23128629
TI  - Response of rock-fissure seepage to snowmelt in Mount Taihang slope-catchment,
      North China.
AB  - The complex physiographic and hydrogeological systems of mountain terrains
      facilitate intense rock-fissure seepages and multi-functional ecological
      interactions. As mountain eco-hydrological terrains are the common water sources
      of river basins across the globe, it is critical to build sufficient
      understanding into the hydrological processes in this unique ecosystem. This
      study analyzes infiltration and soil/rock-fissure seepage processes from a 65 mm
      snowfall/melt in November 2009 in the typical granitic gneiss slope catchment in
      the Taihang Mountains. The snowfall, snowmelt and melt-water processes are
      monitored using soil-water time-domain reflectometry (TDR) probes and tipping
      bucket flowmeters. The results suggest that snowmelt infiltration significantly
      influences soil/rock water seepage in the 0-100 cm soil depth of the slope
      catchment. It is not only air temperature that influences snowmelt, but also
      snowmelt infiltration and rock-fissure seepage. Diurnal variations in rock
      fissure seepage are in close correlation with air temperature (R(2) > 0.7).
      Temperature also varies with soil/rock water viscosity, which element in turn
      influences soil/rock water flow. Invariably, water dynamics in the study area is
      not only a critical water supply element for domestic, industrial and
      agricultural uses, but also for food security and social stability.

PMID- 23128630
TI  - Generalization and formalization of the USEPA procedure for design of treated
      wastewater aquifer recharge basins: I. Theoretical development.
AB  - Groundwater is vulnerable to overdraft and depletion, especially in relatively
      dry regions where natural recharge rates are very low and groundwater is the main
      source of water. Artificial recharge of groundwater with treated wastewater has
      been widely adopted as a technique to replenish the overdraft aquifers. Indeed,
      in the USA, the technique has been practised for a long time. In 1981, a design
      procedure manual was developed for practitioners by the United States
      Environmental Protection Agency (USEPA). It was updated in 1984 and lastly in
      2006. However, the design procedure has not been fully generalized for the
      different situations and has not been fully formalized in order to allow its
      automated implementation on calculation software (i.e. spreadsheet). Therefore,
      in this paper we formalized and generalized the USEPA design procedure to achieve
      an automated iterative method of calculation which can be easily implemented in a
      spreadsheet.

PMID- 23128631
TI  - Improved calcium sulfate recovery from a reverse osmosis retentate using eutectic
      freeze crystallization.
AB  - A novel low temperature crystallization process called eutectic freeze
      crystallization (EFC) can produce both salt(s) and ice from a reverse osmosis
      (RO) stream by operating at the eutectic temperature of a solution. The EFC
      reject stream, which is de-supersaturated with respect to the scaling component,
      can subsequently be recycled back to the RO process for increased water recovery.
      This paper looks at the feasibility of using EFC to remove calcium sulfate from
      an RO retentate stream and compares the results to recovery rates at 0 and 20 
      degrees C. The results showed that there was a greater yield of calcium sulfate
      obtained at 0  degrees C as compared with 20  degrees C. Operation under eutectic
      conditions, with only a 20% ice recovery, resulted in an even greater yield of
      calcium sulfate (48%) when compared with yields obtained at operating
      temperatures of 0 and 20  degrees C (15% at 0  degrees C and 13% at 20  degrees
      C). The theoretical calcium recoveries were found to be 75 and 70% at 0 and 20 
      degrees C respectively which was higher than the experimentally determined
      values. The EFC process has the added advantage of producing water along with a
      salt.

PMID- 23128632
TI  - Dispersion and stability of titanium dioxide nanoparticles in aqueous suspension:
      effects of ultrasonication and concentration.
AB  - The increasing applications of titanium dioxide (TiO(2)) nanoparticles raise
      concerns about their potential environmental impacts. To investigate the fate and
      transport of TiO(2) nanoparticles in aqueous suspension, ultrasonication is
      widely used for the dispersion of TiO(2) nanoparticles in laboratory-scale
      studies. There is a pressing need for detailed information on the dispersion and
      stability of TiO(2) nanoparticles. This study investigated the change of size,
      zeta potential, and pH of TiO(2) nanoparticles aqueous suspension under different
      conditions of ultrasonication and concentrations. It was found that the
      hydrodynamic diameter of TiO(2) nanoparticles decreased with increasing
      suspension concentration and remained stable for more than 1 hour after
      sonication, which is enough for experimental research. The pH decreased with
      increasing nanoparticles concentration. Ultrasonication remarkably improved zeta
      potential to be above 15 mV for all the samples. Therefore, 20 minutes of
      ultrasonication (180 W) is sufficient for the dispersion of this rutile TiO(2)
      nanoparticles suspension, which can remain stable for more than 1 hour. However,
      the optimum sonication time for TiO(2) nanoparticles dispersion is influenced by
      many factors, such as TiO(2) nanoparticles concentration, solution chemistry, and
      sonicator parameters.

PMID- 23128633
TI  - Single-solute and bisolute sorption of phenol and trichloroethylene from aqueous
      solution onto modified montmorillonite and application of sorption models.
AB  - The single-solute and bisolute sorption behaviour of phenol and
      trichloroethylene, two organic compounds with different structures, onto
      cetyltrimethylammonium bromide (CTAB)-montmorillonite was studied. The monolayer
      Langmuir model (MLM) and empirical Freundlich model (EFM) were applied to the
      single-solute sorption of phenol or trichloroethylene from water onto monolayer
      or multilayer CTAB-montmorillonite. The parameters contained in the MLM and EFM
      were determined for each solute by fitting to the single-solute isotherm data,
      and subsequently utilized in binary sorption. The extended Langmuir model (ELM)
      coupled with the single-solute MLM and the ideal adsorbed solution theory (IAST)
      coupled with the single-solute EFM were used to predict the binary sorption of
      phenol and trichloroethylene onto CTAB-montmorillonite. It was found that the EFM
      was better than the MLM at describing single-solute sorption from water onto CTAB
      montmorillonite, and the IAST was better than the ELM at describing the binary
      sorption from water onto CTAB-montmorillonite.

PMID- 23128634
TI  - Use of biogas for cogeneration of heat and electricity for local application:
      performance evaluation of an engine power generator and a sludge thermal dryer.
AB  - A small unit of cogeneration of energy and heat was tested at the Centre for
      Research and Training on Sanitation UFMG/COPASA - CePTS, located at the Arrudas
      Sewage Treatment Plant, in Belo Horizonte, Minas Gerais, Brazil. The unit
      consisted of an engine power generator adapted to run on biogas, a thermal dryer
      prototype and other peripherals (compressor, biogas storage tank, air blower,
      etc.). The heat from engine power generator exhaust gases was directed towards
      the thermal dryer prototype to dry the sludge and disinfect it. The results
      showed that the experimental apparatus is self-sufficient in electricity, even
      producing a surplus, available for other uses. The tests of drying and
      disinfection of sludge lasted 7 h, leading to an increase in solids content from
      4 to 8% (50% reduction in sludge volume). Although the drying of sludge was not
      possible (only thickening was achieved), the disinfection process proved very
      effective, enabling the complete inactivation of helminth eggs.

PMID- 23128635
TI  - Kinetics for ammonium ion removal using a three-dimensional electrode system.
AB  - Electrochemical oxidation of ammonium ions (NH(4)(+)) by using a three
      dimensional electrode (TDE) composed of IrO(2)-Ta(2)O(5)/Ti anode and bamboo
      carbon was carried out in this paper. Experimental results reveal that the
      NH(4)(+) oxidation follows first-order kinetics at lower NH(4)(+) concentration
      and the rate constant is highly dependent on the applied current density, dosage
      of chlorine ions and initial NH(4)(+) concentration. In addition, increasing
      current density, more Cl(-) dosage and higher initial NH(4)(+) concentration are
      beneficial for NH(4)(+) removal. By inspecting the relation between rate constant
      and those operating factors, an overall empirical equation for estimation of the
      rate constant of NH(4)(+) oxidation is presented. The estimated model is in good
      agreement with the experimental results and it could also be used for accurate
      design of the TDE system.

PMID- 23128636
TI  - Anaerobic co-digestion of sewage sludge and primary clarifier skimmings for
      increased biogas production.
AB  - The objective of the study was to identify the impact of co-digesting clarifier
      skimmings on the overall methane generation from the treatment plant and
      additional energy value of the increased methane production. Biogas production
      from co-digesting clarifier skimmings and sewage sludge in pilot-scale fed-batch
      mesophilic anaerobic digesters has been evaluated. The digester was fed with
      increasing quantities of clarifier skimmings loads: 1.5, 2.6, 3.5 and 7.0 g COD
      equivalent/(L.d) (COD: chemical oxygen demand). Average volatile solids reduction
      of 65% was achieved in the scum-fed digester, compared with 51% in the control
      digester. Average 69% COD removal was achieved at highest scum loading (7 g COD
      eq/(L.d)) with approximate methane yield of 250 L CH(4)/kg COD fed (4 ft(3)/lb
      COD fed). The results show that scum as co-substrate in anaerobic digestion
      systems improves biogas yields while a 29% increase in specific CH(4) yield could
      be achieved when scum load is 7 g COD eq/(L.d). Based on the pilot-scale study
      results and full-scale data from South East Water Pollution Control Plant and
      Northeast Water Pollution Control Plant the expected annual energy recovery would
      be approximately 1.7 billion BTUs or nearly 0.5 million kWh.

PMID- 23128637
TI  - Influence of water treatment residuals on dewaterability of wastewater biosolids.
AB  - Co-dewatering of water treatment residuals (WTR) and wastewater biosolids can
      potentially benefit municipalities by reducing processing equipment and costs.
      This study investigated dewaterability (using capillary suction time, CST) of
      combined alum residuals (Al-WTR) and anaerobically digested biosolids at various
      blending ratios (BR), defined as the mass ratio of WTR to biosolids on a dry
      solids basis. Without polymer addition, the CST was 160 s for a BR of 0.75
      compared with 355 s for the biosolids alone. The optimum polymer dose (OPD),
      defined as the polymer dose yielding CST of 20 s, was reduced from 20.6 g kg(-1)
      dry solids for the biosolids alone to 16.3 and 12.6 g kg(-1) when BR was 0.75 and
      1.5, respectively. Precipitated Al hydrous oxides in the WTR likely caused
      flocculation of the biosolids particles through heterocoagulation or charge
      neutralization. The solids contents of the blended materials and biosolids at
      their respective OPDs were not statistically different (alpha = 0.05) following
      dewatering by a belt-filter press. We conclude addition of Al-WTR improved
      biosolids dewaterability and reduced polymer dosage. In practice, the extent of
      these benefits may be limited by the quantity of WTR produced relative to the
      amount of wastewater solids generated by a municipality.

PMID- 23128638
TI  - Effect of co-existing copper and calcium on the removal of As(V) by reused
      aluminum oxides.
AB  - Among the various heavy metals, arsenic is frequently found in abandoned mine
      drainage and the environmental fate of arsenic in real aqueous solutions can be
      highly dependent on the presence of co-existing ions. In this study, removal of
      arsenate through adsorption on the reused aluminum oxide or through precipitation
      was investigated in a single and in a binary system as a function of pH and
      concentration. Different removal behaviors of arsenate were observed in the
      presence of different cations as well as a variation of the molar ratios of
      arsenate to cations. Co-operative effects on arsenate removal by precipitation in
      solution occurred with an increase of copper concentration, while a decrease of
      arsenate removal resulted in increasing calcium concentration. It was observed
      that the arsenate removal in the presence of calcium would be highly dependent on
      the molar ratios of both elements.

PMID- 23128640
TI  - Adsorption of leather dye onto activated carbon prepared from bottle gourd:
      equilibrium, kinetic and mechanism studies.
AB  - Activated carbon prepared from bottle gourd has been used as adsorbent for
      removal of leather dye (Direct Black 38) from aqueous solution. The activated
      carbon obtained showed a mesoporous texture, with surface area of 556.16 m(2) g(
      1), and a surface free of organic functional groups. The initial dye
      concentration, contact time and pH significantly influenced the adsorption
      capacity. In the acid region (pH 2.5) the adsorption of dye was more favorable.
      The adsorption equilibrium was attained after 60 min. Equilibrium data were
      analyzed by the Langmuir, Freundlich, Dubinin-Radushkevich and Temkin isotherm
      models. The equilibrium data were best described by the Langmuir isotherm, with
      maximum adsorption capacity of 94.9 mg g(-1). Adsorption kinetic data were fitted
      using the pseudo-first-order, pseudo-second-order, Elovich and intraparticle
      diffusion models. The adsorption kinetic was best described by the second-order
      kinetic equation. The adsorption process was controlled by both external mass
      transfer and intraparticle diffusion. Activated carbon prepared from bottle gourd
      was shown to be a promising material for adsorption of Direct Black 38 from
      aqueous solution.

PMID- 23128639
TI  - Occurrence, removal and accumulation in sludge of protozoan cysts and helminth
      eggs in a full-scale anaerobic pond in Burkina Faso.
AB  - The present paper investigates the occurrence, removal, and accumulation of
      protozoan cysts and helminth eggs in a large anaerobic pond treating municipal
      wastewater of Ouagadougou (Burkina Faso). With a hydraulic retention time of 6.5
      days, the anaerobic pond achieved 100% removal of helminth eggs and protozoan
      cysts most of the time, except during the hot period. The average residual
      concentrations of helminth eggs and protozoan cysts in the effluent were
      respectively 0.45 eggs/L (minimum 0 and maximum 3), and 5.4 cysts/L (minimum 0
      and maximum 26). Protozoan cysts accumulation in sludge averaged 1,613 cysts/g
      total solids. Ancylostoma duodenale, Ascaris lumbricoides and Hymenolepis nana
      were the main helminth species found in the sludge. After 7 years of operation,
      the sludge in the pond still contained a high level of viable helminth eggs
      evaluated at 42%.

PMID- 23128641
TI  - Impact of some herbicides on the biomass activity in biological treatment plants
      and biodegradability enhancement by a photo-Fenton process.
AB  - In recent years, the use of agrochemicals has increased because they are
      essential for profitable agricultural production. Herbicides are heavily demanded
      compounds and among these, the most marketed are 2,4-D, atrazine and acetochlor.
      They have characteristics that can cause problems to humans and the environment.
      Therefore, it is necessary to design systems that can reduce these compounds to
      harmless molecules. This work aims at evaluating the possibility of incorporating
      these herbicides into degradable effluents in a biological treatment system,
      without reducing its efficiency. For this purpose, studies of organic matter
      degradability in the presence of these agrochemicals were performed. A synthetic
      effluent based on glucose and mineral salts was inoculated with microorganisms.
      Glucose consumption and biomass concentration were assessed. Subsequently,
      preliminary studies were performed to test the viability of degradation of the
      most harmful compound with an advanced oxidation process (AOP). The results
      showed that the incorporation of these herbicides into degradable effluents in a
      biological treatment system has a negative impact on microorganisms. Therefore,
      the application of an AOP, such as the Fenton or photo-Fenton processes, prior to
      a biological treatment was found to degrade these substances to simpler and less
      toxic molecules.

PMID- 23128642
TI  - Remote sensing of suspended solids concentration in a reservoir with frequent
      wildland fires on its watershed.
AB  - Wildland fire is an important disturbance factor that can cause severe ecological
      and watershed damage. Depending on fire severity and watershed extension,
      reservoir suspended solids concentration (SSC), which arrives through river load,
      is expected to increase. Satellite remote sensing is an alternative technique to
      measure SSC in a reservoir. In this paper we evaluate the applicability of
      multitemporal Landsat data for mapping and monitoring of the SSC in a reservoir
      whose watershed was exposed to fires. Besides, we aim to identify catchment areas
      that have been burned, estimating the level of burn severity that occurred
      because of the fire. The Landsat images were radiometrically, atmospherically and
      geometrically corrected. Using the differenced normalized burn ratio (dNBR)
      algorithm, the perimeter and severity of fire was mapped. A theoretical model to
      characterize the distribution of SSC using multitemporal Landsat data was
      developed. The relationship between burn severity maps, rainfall and SSC maps
      improved our understanding of management actions on a reservoir which suffers
      frequent wildfires on its watershed. The theoretical model here developed may be
      considered as a low cost measurement tool for water management authorities,
      particularly when in-situ data are not available.

PMID- 23128643
TI  - WWTP design in warm climates - guideline comparison and parameter adaptation for
      a full-scale activated sludge plant using mass balancing.
AB  - The ATV-A-131 guideline and the design approach published in 'Wastewater
      Engineering, Treatment and Reuse (WE)' are widely used for the design of
      activated sludge plants. They are both based on simplified steady-state
      assumptions tailored to the boundary conditions of temperate climates. Using
      design guidelines beyond the designated temperature range may lead to
      inappropriate results. The objectives of this paper are (1) to summarise
      temperature relevant differences between ATV-A-131 and WE; (2) to show the
      related design components; and (3) to demonstrate a procedure for design
      parameter adaptation for a full-scale activated sludge plant located in a warm
      climate region. To gain steady-state data required for wastewater treatment plant
      (WWTP) design according to ATV-A-131 and WE, full-scale plant data were acquired
      for a period of 6 months as a basis for analyses and adaptation. Mass balances
      were calculated for the verification of the measurements and for analysing excess
      sludge production. The two approaches showed relevant temperature related
      differences. WE default application resulted in lower deviation in the mass
      balance results for excess sludge production. However, with the adaptation of the
      heterotrophic decay rates for both approaches and the inert organic and mineral
      solids fraction additionally for ATV-A-131, a good fit to the observed excess
      sludge production could be achieved.

PMID- 23128644
TI  - AquaCrop model simulation under different irrigation water and nitrogen
      strategies.
AB  - On a global scale, irrigated agriculture consumes about 72% of available
      freshwater resources. Deficit irrigation can be applied in the field to save
      irrigation water and still lead to acceptable crop production. The AquaCrop model
      is a simulation model for management of irrigation and nitrogen fertilizer. This
      model is a new model that is accurate, robust and requires fewer data inputs
      compared with the other models. The purpose of this study was to simulate canopy
      cover, grain yield and water use efficiency (WUE) for soybean using the AquaCrop
      model. A field line source sprinkler irrigation system was conducted under full
      and deficit irrigation using different nitrogen fertilizer applications during
      two cropping seasons for soybean at Gorgan province in Iran. The simulation
      results showed a reasonably accurate prediction of yield, canopy cover and WUE in
      all cases (error less than 23%). The simulated pattern of canopy progression over
      time was close to measured values, with Willmott's index of agreement for all the
      cases being >=0.95 for different parameters. The AquaCrop model has the ability
      to simulate the WUE of soybean under different irrigation water and nitrogen
      applications. This model is a useful tool for managing the crop water
      productivity.

PMID- 23128645
TI  - Neonatal hyperglycaemia increases mortality and morbidity in preterm lambs.
AB  - BACKGROUND: Hyperglycaemic preterm babies suffer increased mortality and
      morbidity, but it is not known if these associations are causal or if treatment
      with insulin improves outcome. OBJECTIVES: We aimed to investigate the effect of
      neonatal hyperglycaemia, and its treatment with insulin, on mortality and
      morbidity in preterm lambs. METHODS: Preterm lambs (137 days' gestation; term =
      148 days) were randomised to a 12-day intravenous infusion of saline (PremC; n =
      39), 50% dextrose (HYPER; n = 47), or 50% dextrose + insulin (INS; n = 21). Term
      controls (TermC; n = 19) received saline. Dextrose and insulin infusions were
      titrated to maintain blood glucose concentrations (BGC) at 10-12 mmol.l(-1)
      (HYPER) or 4-6 mmol.l(-1) (INS). RESULTS: HYPER lambs had higher BGC (mean (SEM);
      TermC: 5.6 (0.1), PremC: 5.5 (0.1), HYPER: 10.8 (0.6), INS: 6.2 (0.3) mmol.l(-1);
      p < 0.0001), higher mortality (n (%); TermC: 0, PremC: 2 (5), HYPER: 11 (23),
      INS: 0; p < 0.001), higher incidence of fever (n (%); TermC: 3 (16), PremC: 13
      (33), HYPER: 26 (55), INS: 6 (29); p = 0.01) and lower weight gain (mean (SEM);
      TermC: 45.9 (2.9), PremC: 44.2 (2.1), HYPER: 28.4 (1.9), INS: 28.7 (2.8) g.kg(
      1).day(-1); p < 0.0001). CONCLUSIONS: Neonatal hyperglycaemia in preterm lambs
      causes increased mortality and morbidity, and decreases growth. Insulin treatment
      to restore euglycaemia attenuated the increased mortality and morbidity, but not
      the decreased growth.

PMID- 23128646
TI  - Use of web 2.0 to recruit Australian gay men to an online HIV/AIDS survey.
AB  - BACKGROUND: Continuous prevention efforts for human immunodeficiency virus (HIV)
      and acquired immune deficiency syndrome (AIDS) are recommended among those men
      who have sex with men (MSM). Creative use of e-technologies coupled with a better
      understanding of social networks could lead to improved health interventions
      among this risk population. OBJECTIVE: The aims of the study were to (1) compare
      the impact of various advertising strategies on recruiting MSM participants to an
      online HIV/AIDS survey, and (2) explore the feasibility of using a social network
      service (SNS) for study advertising. METHODS: A cross-sectional online survey was
      conducted in 2009. South Australian men over 18 years were invited to participate
      if they had had sexual intercourse with men in the previous year. A short
      questionnaire was used to collect demographics and information on sexual
      behavior, HIV history, use of the Internet for dating purposes, and sources of
      health information. The survey was promoted in community settings and online,
      including advertisements through social networks. RESULTS: A total of 243 men
      completed the online survey during the 8-week data collection period. Online
      advertisements recruited 91.7% (220/240) of the sample. Conversely, traditional
      advertisements in the community recruited only 5.8% (14/240) of the sample. Ten
      volunteers were asked to advertise on their personal SNS application, but only 2
      effectively did so. Only 18/240 (7.5%) of the respondents reported having learned
      of our study through the SNS application. In this sample, 19.3% (47/243) of
      participants had never been tested for HIV. Among the participants who had been
      tested, 12.8% (25/196) reported being HIV-positive. Regarding Internet use, 82.3%
      (200/243) of participants had dated online in the previous 6 months. Among the
      participants who had dated online, most (175/200, 87.5%) had found an Internet
      sexual partner and two-thirds (132/200, 66.0%) had had anal sex with these
      partner(s). Among men who had anal sex with an Internet partner, 68.2% (90/132)
      used a condom during sex. CONCLUSIONS: The MSM participants in this study had
      high-risk profiles for HIV and other sexually transmitted diseases (STDs), which
      highlights the need for ongoing health interventions among this group. In this
      study, the SNS marketing strategy did not appear to create a viral effect and it
      had a relatively poor yield.

PMID- 23128648
TI  - Hepatitis, gallbladder hydrops, splenomegaly, and ascites in a child with scarlet
      fever.
AB  - We report a case of scarlet fever associated with hepatitis, gallbladder hydrops,
      splenomegaly, and ascites in a 15-year-old girl. The girl presented with fever
      and skin rash. Leukocyte, liver enzyme, and serum C-reactive protein
      concentrations were elevated. Ultrasonography revealed marked gallbladder wall
      thickening, diffuse liver parenchymal disease with moderate splenomegaly, and
      moderate ascites throughout the abdominal and pelvic cavities. Blood cultures for
      group A beta-hemolytic streptococci were negative. Complete recovery was
      facilitated with antibiotic treatment.

PMID- 23128647
TI  - Most important chronic complications of arteriovenous fistulas for hemodialysis.
AB  - The aim of this review was to highlight the most important complications of
      arteriovenous fistulas (AVFs) for hemodialysis (HD). The quality of vascular
      access for HD should be suitable for repeated puncture and allow a high blood
      flow rate for high-efficiency dialysis with minimal complications. The dialysis
      staff must be well versed in manipulation of the AVF, and there should be a
      minimal need for corrective interventions. Construction of an AVF creates
      conditions for increasing the flow of blood through the venous system.
      Fulfillment of these conditions reduces the risk of turbulence and endothelium
      injury, which, in turn, minimizes the potential for stenosis. An AVF is closest
      to the ideal model of vascular access. The most important complications of
      fistulae for HD are lymphedema, infection, aneurysm, stenosis, congestive heart
      failure, steal syndrome, ischemic neuropathy and thrombosis. In HD patients, the
      most common cause of vascular access failure is neointimal hyperplasia. It is
      important to gain information about early clinical symptoms of AVF dysfunction in
      order to prevent and adequately treat potential complications.

PMID- 23128649
TI  - Psychogenic cough: a diagnosis of exclusion.
AB  - Cough is the most common respiratory symptom and a common reason for consultation
      in both primary care and emergency departments, as a result of family concerns.
      We report an 11-year-old girl who complains of constant cough episode for 4 hours
      without any rest. After sequential treatment with nebulized salbutamol and
      budesonide, dexamethasone, codeine, and midazolam, the patient showed transient
      improvement, with cough disappearing altogether, but 10 minutes later, it started
      over with the same intensity from the beginning. When she got distracted and
      talked, the access decreased, starting again when the word "cough" or similar
      terms were mentioned in front of her. She remained asymptomatic for 2 hours,
      after which her symptoms began similarly to the initial, coinciding with taking 1
      tablet of clarithromycin, so it was decided to start a continuous infusion of
      midazolam, with the cough disappearing completely after 15 minutes of starting
      the infusion. One hour after starting the infusion, the child fell asleep. At
      waking, the cough had disappeared. She continued treatment with oral codeine for
      3 days, showing no relapse. It is important to include psychogenic cough in the
      differential diagnosis of persistent or recurrent chronic cough and asthma that
      is difficult to control and communicate that diagnostic criteria are based on
      indicative symptoms (cough access only when awake), with normal radiology,
      spirometry, and bronchoscopy, to avoid misdiagnosis and inadequate
      pharmacological actions. Successful treatment is based on recognizing the
      underlying cause and use of different forms of cognitive-behavioral therapies
      that aim to break the habit.

PMID- 23128650
TI  - Penetrating injury to the superior sagittal sinus by a nail in a 4-year-old
      child: a case report.
AB  - Penetrating head injuries are rare in children, with most injuries being
      accidental as a result of unsupervised use of sharp objects by young children. We
      present the case of a 4-year-old boy brought to our emergency department with a
      nail embedded through a wooden board and into his skull. The nail was determined
      to be entering the superior sagittal sinus through radiographic imaging. Thus,
      surgical removal of the nail was determined to be necessary. Inspection revealed
      a likely through-and-through injury to the sinus, and therefore, because sinus
      reconstruction was not deemed possible, the sinus was occluded with suture ties
      both in front and behind the nail before nail removal. Postoperatively, the
      patient did well and remained neurologically intact. Investigation for possible
      nonaccidental trauma was conducted. Although most commonly accidental in nature,
      nonaccidental penetrating traumas have been reported in both pediatric and adult
      populations. This patient did well after occlusion of his superior sagittal sinus
      at the coronal suture after penetrating injury by a nail. Penetrating injury in
      the pediatric population is predominantly thought to be accidental, but a high
      index of suspicion should be maintained for possible nonaccidental etiology.

PMID- 23128651
TI  - Right lower-quadrant pain-more than one diagnosis.
AB  - When a patient presents with right-lower-quadrant pain in the emergency room, the
      diagnosis of appendicitis must always be considered, but the differential
      diagnosis for this symptom includes many other etiologies. We describe a case of
      an 8-year-old girl with von Willebrand disease who presented with right-lower
      quadrant pain and was found to have an appendiceal wall hematoma. During her
      evaluation, an ultrasound of the abdomen was performed, and the results were
      initially interpreted as an intussusception. Although ultrasound is a highly
      reliable way to diagnose appendicitis and intussusception, the case illustrates
      that the thickened abdominal wall that occurs in a mural hematoma can appear like
      the "target sign" that is usually associated with intussusception, and in certain
      clinical scenarios, alternative forms of imaging may be of value.

PMID- 23128652
TI  - Atrial fibrillation with wide QRS tachycardia and undiagnosed Wolff-Parkinson
      White syndrome: diagnostic and therapeutic dilemmas in a pediatric patient.
AB  - A 10-year-old girl presented to the emergency department of a regional hospital
      with 1 episode of generalized tonic-clonic seizures. Postictal monitoring
      followed by a 12-lead electrocardiogram showed fast atrial fibrillation with
      intermittent wide QRS regular tachycardia. Immediately following this, her rhythm
      changed to wide QRS irregular tachycardia without hemodynamic compromise. She was
      suspected to have ventricular tachycardia and was treated with intravenous
      amiodarone with cardioversion to sinus rhythm. Subsequent electrocardiogram in
      sinus rhythm showed typical features of manifest Wolff-Parkinson-White (WPW)
      accessory pathway. This case illustrates the diagnostic and therapeutic dilemmas
      in patients with atrial fibrillation, wide QRS tachycardia, and undiagnosed WPW
      syndrome with antidromic conduction of atrial arrhythmias through the accessory
      pathway. Furthermore, this case demonstrates that undiagnosed wide QRS
      tachycardias need to be treated with drugs acting on the accessory pathway, thus
      keeping in mind underlying WPW syndrome as a possibility to avoid potentially
      catastrophic events.

PMID- 23128653
TI  - Retrocardiac pneumonia mimicking acute abdomen: a diagnostic challenge.
AB  - We present the case of a child who showed acute abdominal pain and fever due to
      retrocardiac pneumonia by Streptococcus pneumoniae without respiratory signs and
      symptoms. Acute abdominal pain is a common presenting symptom of children seen in
      pediatric emergency rooms. Basilar pneumonia is an uncommonly known cause of
      pediatric abdominal pain; it may go unrecognized on a patient's initial
      evaluation. Our case suggests that the clinical manifestations of a retrocardiac
      pneumonia can be atypical with abdominal pain as the principal complaint,
      mimicking acute abdomen.

PMID- 23128654
TI  - Unexpected diagnosis of severe coarctation of the aorta after ketamine procedural
      sedation.
AB  - A 12-year-old child presented to the emergency department with a right forearm
      fracture. After administration of an intravenous dose of ketamine for fracture
      reduction, he developed severe hypertension. This sign led us to discover an
      undiagnosed coarctation of the aorta.

PMID- 23128655
TI  - Cultivated child abuse: a 2-year-old with hyponatremic seizures.
AB  - Hyponatremia leading to seizures is well described in children. Hyponatremia is
      defined as a serum sodium of less than 135 mEq/L and can be acute or chronic. The
      seizure threshold in hyponatremia is markedly increased at a level of 125 mEq/L
      or less. Hyponatremia is one of the most common electrolyte disturbances and
      occurs in both the inpatient and outpatient setting. The 3 types of hyponatremia
      are hypovolemic, euvolemic, and hypervolemic. The diagnosis is made through
      serologic and urinary laboratory studies. We present the case of a 2-year-old
      girl with recurrent hyponatremic seizures, who was resuscitated twice within a
      short period at our institution. Her hyponatremia coupled with the seizures was
      initially thought to be secondary to salt-wasting renal disease, adrenal
      insufficiency, or even syndrome of inappropriate antidiuretic hormone secretion.
      The case took an interesting twist, which led us to conclude that this was an
      uncommon yet not unheard of form of child abuse.

PMID- 23128656
TI  - Mercury poisoning: a diagnostic challenge.
AB  - Clinical features of mercury poisoning are nonspecific, and a detailed history is
      very valuable. The silvery, shiny appearance of mercury makes it very exciting
      and attractive for children. The overall half-life of elemental mercury in the
      body averages approximately 2 months. Chelation therapy with dimercaptosuccinic
      acid is the treatment of choice if the urine or blood level of mercury is high or
      the symptoms are profound. Here, we describe a 14-year-old boy with fever,
      respiratory distress, and body rash. Investigation leading to a diagnosis of
      mercury poisoning was made only after his mother presented with the similar
      symptoms a few days later.

PMID- 23128657
TI  - The use of methylprednisolone in acute spinal cord injury: a review of the
      evidence, controversies, and recommendations.
AB  - The use of methylprednisolone after acute spinal cord injury has been under
      discussion for more than 20 years. There is ongoing debate about the efficacy and
      clinical impact of methylprednisolone in recovery from spinal cord injury, and
      studies show considerable variability in practice patterns among surgeons.
      Consensus statements consider methylprednisolone as a treatment option for acute
      spinal cord injury, but not a standard of care based on available evidence. This
      review discusses the evidence from prospective trials of methylprednisolone in
      adults and teenagers after spinal cord injury, consensus statements on the use of
      methylprednisolone, and practice variability in North America and the United
      Kingdom over time.

PMID- 23128659
TI  - Brodie abscess.

PMID- 23128660
TI  - ECGs in the ED.

PMID- 23128661
TI  - Neonatal perforation peritonitis masquerading as acute scrotum: significance of a
      preoperative abdominal X-ray.

PMID- 23128662
TI  - A response to the letter to the editors about "flumazenil administration in
      poisoned pediatric patients".

PMID- 23128663
TI  - Pediatric all-terrain vehicle trauma:  educational measures to stop the epidemic
      before it reaches the pediatric emergency care.

PMID- 23128664
TI  - Site-specific differential effects of once-yearly zoledronic acid on the hip
      assessed with quantitative computed tomography: results from the HORIZON Pivotal
      Fracture Trial.
AB  - We used new approaches to the analysis of diagnostic scans to detect changes in
      bone density in different regions of the hip after 3 years of treatment with the
      zoledronic acid. We showed that the drug significantly increases hip bone density
      compared to placebo at regions where hip fractures usually occur. INTRODUCTION:
      This study aims to identify whether treatment with zoledronic acid exerts site
      specific differential effects on volumetric bone mineral density (vBMD) at the
      hip. METHODS: We analysed quantitative computed tomography scans of the hip
      obtained at baseline and 36 months in 179 women participating in the HORIZON
      Pivotal Fracture Trial. Cortical, trabecular and integral BMDs were determined at
      three main regions of interest-the femoral neck (FN), trochanter (TR) and total
      hip (TH)-and several sub-regions of interest, namely the proximal, middle,
      distal, anterior, posterior, inferomedial and superolateral FN, and the middle
      and distal TR. RESULTS: Volumetric BMD increased significantly (p < 0.05) from
      baseline with zoledronic acid compared to placebo. Trabecular vBMD increased as
      follows: FN, 5.4 %; FN sub-regions, 6.0 % (proximal), 4.4 % (middle), 5.6 %
      (distal), 7.5 % (anterior), 7.0 % (superolateral) and 5.4 % (posterior); TR, 6.5
      % and TH, 5.7 %. Cortical vBMD increased as follows: FN sub-regions, 5.0 %
      (proximal FN) and 2.3 % (anterior); TR, 4.6 %; middle TR, 2.7 % and TH, 3.8 %.
      CONCLUSIONS: The effects on vBMD of annual infusion of 5 mg of zoledronic acid
      are site-specific and dominated by trabecular changes.

PMID- 23128665
TI  - Effects of probucol on angiotensin II-induced BMP-2 expression in human umbilical
      vein endothelial cells.
AB  - Bone morphogenetic protein-2 (BMP-2) participates significantly in vascular
      development and pathophysiological processes. Angiotensin II (AngII) has been
      demonstrated to be critical in the initiation and progression of atherosclerosis.
      However, the effects of AngII on BMP-2 expression and of probucol on the AngII
      induced BMP-2 expression in human umbilical vein endothelial cells (HUVECs) are
      unknown. The aim of our study was to investigate these effects. HUVECs were
      cultured and stimulated with various agents. The total superoxide dismutase (SOD)
      activity and the concentrations of malondialdehyde (MDA) and BMP-2 were measured
      by standard methods. Northern blotting was used to detect the expression of BMP-2
      mRNA. The activation of NF-kappaB in the HUVECs was also determined. The AngII
      treatment significantly increased BMP-2 expression levels and activated NF
      kappaB. These effects were suppressed by treatment with pyrrolidine
      dithiocarbamate (PDTC) or probucol. Furthermore, the increased levels of MDA in
      the conditioned medium and the decrease in the total SOD activity caused by the
      AngII treatment were reversed by treatment with probucol or PDTC. Probucol
      downregulated the AngII-induced BMP-2 expression. These effects of probucol may
      be mediated by the inhibition of NF-kappaB activation. 

PMID- 23128666
TI  - Pleiotropic effects of long-term monotherapy with rosuvastatin in dogs with
      moderate heart failure.
AB  - OBJECTIVE: The objective of this study was to investigate the potential
      pleiotropic effects of rosuvastatin (RSV) in the left ventricular (LV) myocardium
      of dogs with moderate heart failure (HF). METHODS: LV tissue was obtained from HF
      dogs randomized to 3 months therapy with low-dose RSV (n = 7), high-dose RSV (n =
      7) or to no therapy (Control, n = 7) and from 7 normal dogs. mRNA and protein
      expression of prohypertrophic mediator NGFI-A binding protein 1 (Nab1),
      phosphatase and tensin homolog (PTEN), phosphoinositide-3 kinase (PI3K) and
      mammalian target of rapamycin (mTOR) were measured, as well as that of
      proinflammatory cytokine interleukin-6 (IL-6), bone marrow-derived stem cell
      markers cKit and Sca1, vascular endothelial and fibroblast growth factors (VEGF
      and FGF) and nitric oxide synthase (NOS) isoforms. RESULTS: Nab1, PTEN, PI3K,
      mTOR and IL-6 increased in the controls. High-dose RSV reduced expression of
      Nab1, PTEN, PI3K, mTOR and IL-6 to near-normal levels. cKit and Sca1
      significantly increased, while VEGF and FGF decreased in the controls compared to
      the normal dogs. RSV therapy further increased expression of cKit, Sca1, VEGF and
      FGF. High-dose RSV normalized the expression of NOS isoforms. CONCLUSION: These
      pleiotropic effects of RSV may account, in part, for the observed beneficial
      effect of RSV on LV function and structural remodeling.

PMID- 23128667
TI  - Exercise in the community for people with minimal gait impairment due to MS: an
      assessor-blind randomized controlled trial.
AB  - BACKGROUND: While there is an increasing body of evidence supporting the efficacy
      of exercise in people with multiple sclerosis (MS), additional information on the
      effectiveness of combining aerobic and resistance training, and yoga is required.
      OBJECTIVES: This study evaluated the effectiveness of community exercise
      interventions for people with MS having minimal gait impairment. METHODS: A multi
      centred, block-randomised, assessor-blinded, controlled trial was conducted.
      Participants were randomised in groups of eight to physiotherapist (PT)-led
      exercise (n = 80), yoga (n = 77), fitness instructor (FI)-led exercise (n = 86)
      and they took part in weekly community-based group exercise sessions. Those in
      the control group were asked not to change of their exercise habits (n = 71). The
      primary outcome was the Multiple Sclerosis Impact Scale (MSIS) 29v2 physical
      component, measured before and after the 10-week intervention. Secondary outcomes
      were the MSIS 29v2 psychological component, the Modified Fatigue Impact Scale
      (MFIS) and the 6-Minute Walk Test (6MWT). RESULTS: The group x time interaction
      approached significance for the MSIS-29v2 physical component (f = 2.48, p =
      0.061) and MFIS total (f = 2.50, p = 0.06), and it was significant for the MFIS
      physical subscale (f = 4.23, p = 0.006). All three exercise interventions led to
      a statistically significant improvement on the MSIS-29 psychological component
      and both the MFIS total and physical subscales, which were greater than the
      control (p < 0.05). Only the PT-led and FI-led interventions significantly
      improved the MSIS-29 physical and 6MWT to levels greater than the control (p <
      0.05). CONCLUSIONS: This study provides evidence for the positive effect of
      exercise on the physical impact of MS and fatigue. The group nature of the
      classes may have contributed to the positive effects seen on the psychological
      impact of MS.

PMID- 23128668
TI  - Acute disseminated encephalomyelitis followed by recurrent or monophasic optic
      neuritis in pediatric patients.
AB  - BACKGROUND: Some pediatric patients with inflammatory demyelinating central
      nervous system disorders cannot be classified under any of the established
      disease entities, making their treatment and prognosis difficult. OBJECTIVE: The
      objective of this study is to characterize a subgroup of pediatric patients with
      recurrent demyelinating central nervous system disorders. METHODS: This study
      includes a case series of pediatric patients with monophasic or recurrent acute
      disseminated encephalomyelitis (ADEM) who later presented with either monophasic
      or recurrent optic neuritis (ON). RESULTS: We describe seven patients with a
      median follow-up of six years (five females, two males) who presented at a median
      age of 6 years (range 4-8 years) with monophasic (n = 4) or recurrent ADEM (two
      to four attacks) followed by monophasic (n = 3) or recurrent ON (two to nine
      attacks). Cranial magnetic resonance imaging (MRI) was typical for ADEM (n = 6)
      with complete or almost complete resolution of lesions on follow-up.
      Cerebrospinal (CSF) studies at the time of ADEM showed a pleocytosis in six
      patients and were negative for oligoclonal bands (OCBs) in all. In all patients
      high titers for serum anti-MOG antibodies were detected. CONCLUSION: ADEM
      followed by ON is a rare but distinct clinical phenotype among pediatric
      patients. Further studies are needed to allow recommendations on treatment or
      prognosis.

PMID- 23128670
TI  - Preparation and characterization of NiW-nHA composite catalyst for hydrocracking.
AB  - The synthesis, characterization and catalytic capability of the NiW-nano
      hydroxyapatite (NiW-nHA) composite were investigated in this paper. The NiW-nHA
      catalyst was prepared by a co-precipitation method. Then Fourier transform
      infrared (FT-IR) spectroscopy, transmission electron microscopy (TEM), X-ray
      diffraction (XRD) and energy dispersive spectroscopy (EDX) were used to analyze
      this material. In addition, the catalytic capacity of the NiW-nHA composite was
      also examined by FT-IR and gas chromatography (GC). The results of FT-IR analysis
      indicated that Ni, W and nHA combined closely. TEM observation revealed that this
      catalyst was needle shaped and the crystal retained a nanometer size. XRD data
      also suggested that a new phase of CaWO(4) appeared and the lattice parameters of
      nHA changed in this system. nHA was the carrier of metals. The rates of Ni/W
      loading were 73.24% and 65.99% according to the EDX data, respectively.
      Furthermore, the conversion of 91.88% Jatropha oil was achieved at 360  degrees C
      and 3 MPa h(-1) over NiW-nHA catalyst. The straight chain alkanes ranging from
      C(15) to C(18) were the main components in the production. The yield of C(15)
      C(18) alkanes was up to 83.56 wt%. The reaction pathway involved hydrocracking of
      the C?C bonds of these triglycerides from Jatropha oil. This paper developed a
      novel non-sulfided catalyst to obtain a "green biofuel" from vegetable oil.

PMID- 23128671
TI  - Maleimide activation of photon upconverting nanoparticles for bioconjugation.
AB  - Photon upconverting nanoparticles (UCNPs) have become an important new  class of
      optical labels. Their unique property of emitting visible light after photo
      excitation with near-infrared radiation enables biological imaging without
      background interference or cell damage. Biological applications require UCNPs
      that are dispersible in water and allow the attachment of biomolecules. Oleic
      acid-coated UCNPs obtained by solvothermal synthesis were functionalized with
      both hydrophilic PEG and thiol-reactive maleimides, either by ligand exchange or
      by silanization. Three different types of maleimide-functionalized UCNPs were
      prepared and characterized by transmission electron microscopy, dynamic light
      scattering and Raman spectroscopy. Ligand exchange of oleic acid by maleimide-PEG
      COOH yielded UCNPs that did not aggregate, were colloidally stable and reacted
      readily with proteins. Such luminescent labels are required for background-free
      imaging and many other bioanalytical applications.

PMID- 23128672
TI  - Downregulation of ubiquitin E3 ligase TNF receptor-associated factor 7 leads to
      stabilization of p53 in breast cancer.
AB  - p53 is a key tumor suppressor and a master regulator of various signaling
      pathways, such as those related to apoptosis, cell cycle and DNA repair. In this
      study, we found a pronounced cytosolic accumulation of the p53 protein in a panel
      of breast cancer specimens. Several mutations lead to p53 accumulation by
      disruption of MDM2-mediated p53 degradation. However, gene sequencing revealed no
      p53 mutation in the majority of our samples. Through search for other possible
      p53 E3 ligases by mRNA and protein expression analysis, downregulation of TNF
      receptor-associated factor 7 (TRAF7) expression was found in these breast tumors.
      We further identified TRAF7 as an E3 ligase for K48-linked ubiquitination of p53
      in vitro. These results suggested that the p53 accumulation was due to the
      defects of TRAF7-mediated ubiquitination. The downregulation of TRAF7 also
      correlated with poor prognosis in a breast cancer cohort. Collectively, TRAF7
      mediated ubiquitination of p53 plays a critical role in breast cancer
      development, and these insights may aid in the development of novel therapeutic
      strategies for breast cancer.

PMID- 23128673
TI  - Molecular basis of the acetyltransferase activity of MEC-17 towards alpha
      tubulin.

PMID- 23128674
TI  - Caught in translation: innate restriction of HIV mRNA translation by a schlafen
      family protein.
AB  - Human immunodeficiency virus type 1 (HIV-1) is the cause of AIDS. In recent years
      it has emerged that cellular interferon-stimulated genes (ISG), play important
      roles in cell-intrinsic restriction of HIV replication. A publication now
      describes a novel strategy employed by HIV-infected cells to restrict viral
      replication, which involves inhibition of viral mRNA translation by the ISG
      Schlafen 11.

PMID- 23128675
TI  - Genetic analysis of polymorphisms in dopamine receptor and transporter genes for
      association with smoking among cancer patients.
AB  - BACKGROUND: Smoking among Russian cancer patients may be related to variations in
      the DRD2/ANKK1 (Taq1), DRD4 (exon III VNTR), and SLC6A3 genes. METHODS: Seven
      hundred fifty patients provided smoking history and DNA. RESULTS: Current smokers
      were more likely to be DRD2 A2 allele carriers versus nonsmokers (former/never
      smokers; 69 vs. 56%; OR = 1.69; 95% CI 1.13-2.53, p = 0.01) and former smokers
      (69 vs. 59%; OR = 1.54; 95% CI 0.97-2.46, p = 0.07). Ever smokers (current/former
      smokers) were more likely to be DRD2 A2 allele carriers versus never smokers (65
      vs. 55%; OR = 1.50; 95% CI 1.00-2.27, p = 0.05). The risk of current smoking
      among DRD2 A2 allele carriers was present if the DRD4 short allele was also
      present (OR = 1.76; 95% CI 1.12-2.78, p = 0.02), and the risk of ever smoking
      among DRD2 A2 allele carriers was present if the DRD4 short allele was also
      present (OR = 1.62; 95% CI 1.02-2.55, p = 0.04). DRD2 A2 allele carriers had a
      shorter period of previous abstinence versus DRD2 A1 carriers (p = 0.02). Effects
      were not statistically significant when controlling for multiple comparisons.
      CONCLUSIONS: The DRD2 A2 allele may increase the risk of smoking among cancer
      patients, convergent with studies using non-Western samples. However, additional
      replication is needed.

PMID- 23128678
TI  - [About nurse psychiatry speciality].

PMID- 23128676
TI  - Prevalence and predictors of smoking by inpatients during a hospital stay.
AB  - BACKGROUND: Accredited US hospitals prohibit smoking inside hospital buildings.
      Patients are expected to abstain from smoking throughout their hospitalization,
      but how many do so is unclear. Smoking by inpatients may compromise patient
      safety, clinical outcomes, and hospital efficiency. METHODS: We conducted an
      observational study of adult cigarette smokers visited by a tobacco counselor
      while hospitalized and reached for telephone follow-up in the 2 weeks after
      discharge. We assessed smoking during the hospital stay at the time of counseling
      for all patients and at follow-up for those reached. We used generalized linear
      models to estimate adjusted relative risk (ARR) for smoking while hospitalized,
      adjusted by patient and admission characteristics. RESULTS: From May 1, 2007,
      through April 31, 2010, counselors visited 5399 smokers, of whom 14.9% had smoked
      between admission and the visit. Of 3555 eligible smokers who consented to follow
      up, 2185 were reached. Smoking at any time during the hospitalization was
      reported by 18.4%, less often during winter months than the rest of the year
      (14.4% vs 19.7%, P = .007). Smoking at any time while hospitalized was less
      common among those 50 years or older (ARR, 0.74; 95% CI, 0.62-0.88), those
      admitted to a cardiac unit (0.64; 0.51-0.81), and those intending to quit after
      discharge (0.46; 0.34-0.63) and more common among those with longer stays (1.36;
      1.14-1.62) and those experiencing cigarette cravings (moderate: 1.23; 1.14-1.33;
      severe: 1.25; 1.18-1.34). Nicotine replacement therapy ordered the day of
      admission was associated with less smoking before the counselor's visit (ARR,
      0.83; 95% CI, 0.72-0.96) but not for the entire hospital stay. CONCLUSIONS:
      Nearly one-fifth of smokers admitted to a smoke-free hospital smoked during their
      hospital stay. Ordering nicotine replacement therapy routinely at admission and
      ongoing monitoring of patients' cigarette cravings might reduce smoking among
      admitted patients.

PMID- 23128677
TI  - Expression and the clinical significance of hPTTG1 in gastric cancer.
AB  - The aim of this study was to investigate the expression and clinical significance
      of hPTTG1 in gastric cancer. Immunohistochemistry was performed to determine the
      expression of hPTTG1 in gastric cancer tissues. Results showed that the positive
      expression of hPTTG1 in gastric cancer tissues was 60.00%, while in adjacent
      normal tissues it was 17.78%. The expression of hPTTG1 was correlated with
      differentiation levels, clinical classification and lymph node metastasis, but
      did not correlate with gender, age or pathological types. hPTTG1 was, therefore,
      overexpressed in gastric cancer tissues. The progression of gastric cancer was
      found to be correlated with the upregulation of the expression of hPTTG1. hPTTG1
      detection may be helpful in evaluating the ability of the clinical classification
      and lymph node metastasis in gastric cancer to predict outcomes. These factors
      act as indicators of the biological behavior of gastric cancer and are fairly
      good markers for prognosis and therapy. 

PMID- 23128679
TI  - [The use of psychotropic drugs in prison (CP Madrid III)].
AB  - The use of psychotropic drugs in primary care has exponentially increased and
      prisons are no exception. These drugs are often prescribed in order to find
      therapeutic uses in the fields of personality disorders, addictions, and
      dysfunctional behaviours that have not been accepted as indications (compassive
      use). This study enabled us to make a detailed description of the use of
      psychiatric drugs at the Madrid III prison, a centre with one of the lowest
      levels of pharmaceutical expenditure in the region. For a two-week period, all
      prescriptions of psychotropic drugs were collected and registered along with data
      of several possible conditioning factors. 20.5% of the population was receiving
      some kind of psychiatric drug; 76% of those inmates undergoing treatment were
      receiving one or two psychotropic drugs; 65% were taking sedatives, 38%
      antidepressants and 27% antipsychotic medication. The total amount of
      psychotropics consumed was 9,840 DDDs, 46% of which were sedatives, 17% of those
      being antidepressants and the other 14% antipsychotics. The total cost of the
      fortnight's treatment was 5,379 euros, 72% of which was spent on antipsychotic
      medication. There are signs that compassive use of the latest generation of
      antipsychotics and antiepileptics, and the newer antidepressants are a main cause
      of the dramatic increase in cost, and cost efficiency has not always been clearly
      demonstrated. One of the key influencing factors on amount, type and cost of
      treatment was the prescriptor. An unexpected result was that of finding no
      relationship between age, nationality, grade or other individual variables and
      prescription of different kind of medication, with the exception of
      benzodiazepines.

PMID- 23128680
TI  - [Autonomy and patient prisoners].
AB  - The authors study a recent Spanish High Court decision declaring liability on the
      Administration's part for the death of an inmate in a prison hospital. We analyse
      the Court's decision using legal, ethical, medical and social perspectives. The
      conclusions are that: 1. the Administration has no legitimate right to force a
      prisoner to take medical treatment, except in circumstances in which there is a
      grave and definite risk to the patient's life, or when the patient lacks capacity
      or when there is the risk of harm to the health of third parties; 2. That in the
      case of health decision making that might affect a patient, the Court has mounted
      a frontal attack on the autonomy of patients in prison; 3. That from a medical
      point of view the decision is discriminatory since it does not apply the same
      standards of measurement to all chronic illnesses that might be found in the
      prison context; 4. That it is inapplicable in daily practice due to the fact that
      its strictness of application would seriously affect the already highly fragile
      ordered coexistence that exists in a prison.

PMID- 23128681
TI  - [From the myth of narcissus to personality disorders in aragonese prisons: an
      introductory profile of personality disorders amongst people deprived of their
      liberty].
AB  - Personality Disorders are important pathologies in the prison context and
      awareness of their existence is necessary for several reasons: the high
      prevelance of PDs amongst inmates, their high level of comorbidity with other
      mental and addictive disorders, and for the link between PD and impulsive
      behaviour and possible violence. A study was carried out in prisons in the
      province of Zaragoza (Spain). The sample consisted of 236 inmates, 25% of whom
      were women. The abbreviated "International Personality Disorder Examination"
      (IPDE) questionnaire proved to be a useful defining tool for this pathology.

PMID- 23128682
TI  - [Cartas].

PMID- 23128683
TI  - [Patologia oral en el paciente VIH positivo].

PMID- 23128684
TI  - [Cirugia menor en un centro penitenciario tipo: Extraccion quirurgica de una
      bala].

PMID- 23128685
TI  - Current management of congenital branchial cleft cysts, sinuses, and fistulae.
AB  - PURPOSE OF REVIEW: Branchial anomalies comprise approximately 20% of pediatric
      congenital head and neck lesions. This study reviews current literature detailing
      the diagnosis and management of first, second, third and fourth branchial cysts,
      sinuses and fistulae. RECENT FINDINGS: Branchial anomalies remain classified as
      first, second, third and fourth cysts, sinuses and fistulae. Management varies on
      the basis of classification. The imaging study of choice remains controversial.
      Computed tomography fistulography likely best demonstrates the complete course of
      the tract if a cutaneous opening is present. Treatment of all lesions has
      historically been by complete surgical excision of the entire tract. Studies of
      less invasive procedures for several anomalies are promising including
      sclerotherapy and endoscopic excision of second branchial cysts, and endoscopic
      cauterization or sclerotherapy at the piriform opening for third and fourth
      branchial sinuses. An increased risk of complications in children less than 8
      years is reported in children undergoing open excision of third and fourth
      branchial anomalies. SUMMARY: Branchial anomalies are common congenital pediatric
      head and neck lesions but are comprised by several diverse anomalies. Treatment
      must be tailored depending on which branchial arch is involved and whether a cyst
      mass or sinus/fistula tract is present.

PMID- 23128687
TI  - Measurement of thermo-elastic deformation of an optic using a polarization-based
      shearing interferometer.
AB  - A shearing interferometer is presented that uses polarization control to shear
      the wavefront and to modulate the interference pattern. The shear is generated by
      spatial walk-off in a birefringent crystal. By adjusting the orientation of the
      birefringent crystal, the components of the wavefront gradient can be
      independently measured to allow determination of the full wavefront vector
      gradient as well as reconstruction of the wavefront. Further, the monolithic
      nature of the crystal used for shearing allows the interferometer to be set up
      without need for precise alignment of any components. An algorithm incorporating
      homodyne detection is presented, which analyzes the modulated interferograms to
      determine the components of the wavefront gradient, from which the wavefront is
      reconstructed. The thermal deformation of a mirror subject to heating from
      absorption of a Gaussian pump beam was accurately observed with a sensitivity
      better than lambda/160. We show that this sensitivity is scale invariant, and
      present a method to account for the nonuniform spatial frequency response of the
      interferometer.

PMID- 23128686
TI  - Cochlear implantation in unique pediatric populations.
AB  - PURPOSE OF REVIEW: Over the last decade, the selection criteria for cochlear
      implantation have expanded to include children with special auditory, otologic,
      and medical problems. Included within this expanded group of candidates are those
      children with auditory neuropathy spectrum disorder, cochleovestibular
      malformations, cochlear nerve deficiency, associated syndromes, as well as
      multiple medical and developmental disorders. Definitive indications for cochlear
      implantation in these unique pediatric populations are in evolution. This review
      will provide an overview of managing and habilitating hearing loss within these
      populations with specific focus on cochlear implantation as a treatment option.
      RECENT FINDINGS: Cochlear implants have been successfully implanted in children
      within unique populations with variable results. Evaluation for cochlear implant
      candidacy includes the core components of a full medical, audiologic, and speech
      and language evaluations. When considering candidacy in these children,
      additional aspects to consider include disorder-specific surgical considerations
      and child/caregiver counseling regarding reasonable postimplantation outcome
      expectations. SUMMARY: Cochlear implants are accepted as the standard of care for
      improving hearing and speech development in children with severe-to-profound
      hearing loss. However, children with sensorineural hearing loss who meet
      established audiologic criteria for cochlear implantation may have unique
      audiologic, medical, and anatomic characteristics that necessitate special
      consideration regarding cochlear implantation candidacy and outcome.
      Individualized preoperative candidacy and counseling, surgical evaluation, and
      reasonable postoperative outcome expectations should be taken into account in the
      management of these children.

PMID- 23128688
TI  - Influence of wavelength-dependent-loss on dispersive wave in nonlinear optical
      fibers.
AB  - In this work, we study numerically the influence of wavelength-dependent loss on
      the generation of dispersive waves (DWs) in nonlinear fiber. This kind of loss
      can be obtained, for instance, by the acousto-optic effect in fiber optics. We
      show that this loss lowers DW frequency in an opposite way that the Raman effect
      does. Also, we see that the Raman effect does not change the DW frequency too
      much when wavelength-dependent loss is included. Finally, we show that the DW
      frequency is not practically affected by fiber length.

PMID- 23128689
TI  - Enhancement of field-analyte interaction at metallic nanogap arrays for sensitive
      localized surface plasmon resonance detection.
AB  - We investigated the near-field enhancement of a localized surface plasmon
      resonance (LSPR) structure based on gold nanograting pairs with a nanosized gap.
      The results calculated by finite-difference time-domain and rigorous coupled-wave
      analysis methods presented that the nanogap enclosed by two neighboring
      nanogratings produced significant confinement and enhancement of electromagnetic
      fields and allowed a sensitive detection in sensing of surface binding events.
      Gold gratings with a narrow gap distance less than 10 nm showed enhanced
      refractive index sensitivity due to the intensified optical field at the nanogap,
      outperforming the LSPR structure with noninteracting nanogratings. Also, we
      analyzed the effectiveness of using an overlap integral (OI) between analyte and
      local plasmon field to estimate the detection sensitivity. We found a strong
      correlation of field-analyte OI with far-field sensor sensitivity.

PMID- 23128690
TI  - Simulation model based approach for long exposure atmospheric point spread
      function reconstruction for laser guide star multiconjugate adaptive optics.
AB  - This paper discusses an innovative simulation model based approach for long
      exposure atmospheric point spread function (PSF) reconstruction in the context of
      laser guide star (LGS) multiconjugate adaptive optics (MCAO). The approach is
      inspired from the classical scheme developed by Veran et al. [J. Opt. Soc. Am.
      A14, 3057 (1997)] and Flicker et al. [Astron. Astrophys.400, 1199 (2003)] and
      reconstructs the long exposure optical transfer function (OTF), i.e., the Fourier
      transformed PSF, as a product of separate long-exposure tip/tilt removed and
      tip/tilt OTFs, each estimated by postprocessing system and simulation telemetry
      data. Sample enclosed energy results assessing reconstruction accuracy are
      presented for the Thirty Meter Telescope LGS MCAO system currently under design
      and show that percent level absolute and differential photometry over a 30 arcsec
      diameter field of view are achievable provided the simulation model faithfully
      represents the real system.

PMID- 23128691
TI  - Improvement of least-squares integration method with iterative compensations in
      fringe reflectometry.
AB  - Least-squares integration is one of the most effective and widely used methods
      for shape reconstruction from gradient data, which result from gradient
      measurement techniques. However, its reconstruction accuracy is limited due to
      the imperfection of the Southwell grid model, which is commonly applied in the
      least-squares integration method. An operation with iterative compensations is
      therefore proposed, especially for the traditional least-squares integration
      method, to improve its integration accuracy. Simulation and experiment are
      carried out to verify the feasibility and superiority of the proposed operation.
      This compensatory operation with iterations is suggested, and its good
      performance on integration accuracy improvement is shown.

PMID- 23128692
TI  - Variable ultrabroadband and narrowband composite polarization retarders.
AB  - We propose and experimentally demonstrate novel types of composite sequences of
      half-wave and quarter-wave polarization retarders, permitting operation at either
      ultrabroad spectral bandwidth or narrow bandwidth. The retarders are composed of
      stacked standard half-wave retarders and quarter-wave retarders of equal
      thickness. To our knowledge, these home-built devices outperform all commercially
      available compound retarders, made of several birefringent materials.

PMID- 23128693
TI  - Theoretical and experimental investigation of generating pulsed Bessel-Gauss
      beams by using an axicon-based resonator.
AB  - Nondiffracting Bessel-Gauss beams are assumed as the superposition of infinite
      numbers of Gaussian beams whose wave vectors lie on a cone. Based on such a
      description, different methods are suggested to generate these fields. In this
      paper, we followed an active scheme to generate these beams. By introducing an
      axicon-based resonator, we designed the appropriate resonator, studied its
      resonance modes, and analyzed the beam propagation outside the resonator.
      Experimentally, we succeeded to obtain Bessel-Gauss beams of the first kind and
      zero order. We also investigated the changes in effective parameters on the
      output beam, both theoretically and experimentally.

PMID- 23128694
TI  - Optical bistability based on an analog of electromagnetically induced
      transparency in plasmonic waveguide-coupled resonators.
AB  - We have investigated numerically an optical bistability effect based on an analog
      of electromagnetically induced transparency (EIT) in a nanoscale plasmonic
      waveguide-coupled resonator system. The system consists of a metal-insulator
      metal waveguide side-coupled with a slot cavity and a nanodisk cavity containing
      Kerr nonlinear material. By finite-difference time-domain simulations, the EIT
      like spectral peak has a redshift with an increase of the dielectric constant of
      the nanodisk cavity. More importantly, we have achieved an optical bistability
      with threshold intensity about three times lower than that of recent literature
      [Appl. Opt.50, 5287 (2011)]. The results show that our plasmonic structure can
      find more excellent application in highly integrated optical circuits, especially
      all-optical switching.

PMID- 23128695
TI  - Stokes scattering matrix for human skin.
AB  - We use a layered model of normal human skin based on size distributions of
      polydisperse spherical particles and their complex refractive indices to compute
      the Stokes scattering matrix at wavelengths in the visible spectral band. The
      elements of the Stokes scattering matrix are required in a polarized radiative
      transfer code for a coupled air-tissue system to compute the polarized
      reflectance and examine how it is dependent on the vertical structure of the
      inherent optical properties of skin, including the phase matrix. Thus, the
      elements of the Stokes scattering matrix can be useful for investigating
      polarization-dependent light propagation in turbid optical media, such as human
      skin tissue.

PMID- 23128696
TI  - Spectral polarization of clear and hazy coastal skies.
AB  - Linear polarization of the clear daytime sky has often been measured as a
      spectrally integrated or quasi-monochromatic variable, but seldom as a spectral
      one. So we use a hyperspectral imaging system to measure skylight polarization at
      high spectral and angular resolutions for clear and hazy skies at our coastal
      site. The resulting polarization maps and spectra exhibit both commonalities and
      differences that seem unexplained by an existing polarized radiative transfer
      model. Comparing the measured polarization spectra with those predicted by
      aerosol single scattering suggests some basic verisimilitude tests for improving
      such models.

PMID- 23128697
TI  - Simulation of atmospheric turbulence for optical systems with extended sources.
AB  - In this paper, the method of random wave vectors for simulation of atmospheric
      turbulence is extended to 2D*2D space to provide spatial degrees of freedom at
      both input and output planes. The modified technique can thus simultaneously
      simulate the turbulence-induced log-amplitude and phase distortions for optical
      systems with extended sources either implemented as a single large aperture or
      multiple apertures. The reliability of our simulation technique is validated in
      different conditions and its application is briefly investigated in a multibeam
      free-space optical communication scenario.

PMID- 23128699
TI  - Target recognition of ladar range images using even-order Zernike moments.
AB  - Ladar range images have attracted considerable attention in automatic target
      recognition fields. In this paper, Zernike moments (ZMs) are applied to classify
      the target of the range image from an arbitrary azimuth angle. However, ZMs
      suffer from high computational costs. To improve the performance of target
      recognition based on small samples, even-order ZMs with serial-parallel
      backpropagation neural networks (BPNNs) are applied to recognize the target of
      the range image. It is found that the rotation invariance and classified
      performance of the even-order ZMs are both better than for odd-order moments and
      for moments compressed by principal component analysis. The experimental results
      demonstrate that combining the even-order ZMs with serial-parallel BPNNs can
      significantly improve the recognition rate for small samples.

PMID- 23128698
TI  - Compensation of the laser parameter fluctuations in large ring-laser gyros: a
      Kalman filter approach.
AB  - He-Ne ring-laser gyroscopes are, at present, the most precise devices for
      absolute angular velocity measurements. Limitations to their performance come
      from the nonlinear dynamics of the laser. Following Lamb semiclassical theory, we
      find a set of critical parameters affecting the time stability of the system. We
      propose a method for estimating the long-term drift of the laser parameters and
      for filtering out the laser dynamics effects from the rotation measurement. The
      parameter estimation procedure, based on the perturbative solutions of the laser
      dynamics, allows us to apply Kalman filter theory for the estimation of the
      angular velocity. Results of a comprehensive Monte Carlo simulation and results
      of a preliminary analysis on experimental data from the ring-laser prototype G
      Pisa are shown and discussed.

PMID- 23128700
TI  - Analysis of noisy dynamic light scattering data using constrained regularization
      techniques.
AB  - Dynamic light scattering (DLS) from colloidal particles often contains noise,
      which makes inversion of the correlation function to obtain the particle size
      distribution (PSD) unreliable. In this work, poor-quality correlation function
      data with baseline error were analyzed using constrained regularization
      techniques. The effect of baseline error was investigated, and two strategies
      were proposed to compensate for baseline error. One strategy is based on edge
      proportion detection of spurious peaks at large size in the PSD, and the other is
      based on the solution norm. Results from simulated and experimental data
      demonstrate the effectiveness of our proposed strategies. The L-curve rules for
      standard Tikhonov and for constrained regularization, the generalized cross
      validation (GCV) rule, and the robust GCV rule were investigated for
      determination of the regularization parameter. A comparison of these rules was
      done using both simulated and experimental data. It is shown that correction of
      baseline error with baseline compensation as well as a reasonable regularization
      parameter choice improves the accuracy of PSD recovery in poor-quality DLS data
      analysis.

PMID- 23128701
TI  - Windowed phase unwrapping using a first-order dynamic system following iso-phase
      contours.
AB  - In this work, we show a windowed phase-unwrapping technique that uses a first
      order dynamic system and scans the phase following its iso-phase contours. In
      previous works, we have shown that low-pass first-order dynamic systems are very
      robust and useful in phase-unwrapping problems. However, it is well known that
      all phase-unwrapping methods have a minimum signal-to-noise ratio that they
      tolerate. This paper shows that scanning the phase within local windows and using
      a path following strategy, the first-order unwrapping method increases its
      tolerance to noise. In this way, using the improved approach, we can unwrap phase
      maps where the basic dynamic phase-unwrapping system fails. Tests and results are
      given, as well as the source code in order to show the performance of the
      proposed method.

PMID- 23128702
TI  - Assessment of some experimental and image analysis factors for background
      oriented schlieren measurements.
AB  - Quantitative measurements of fluid flow properties can be achieved by background
      oriented schlieren (BOS). In this paper, it is shown that this depends on several
      factors. Image-quality index is used to investigate the influence of the image
      sensor and the quality of its output. Image evaluation is applied to synthetic
      images, which are treated with a step function, so that they simulate the sharp
      density jump. The gradual change of the evaluated vector shift revealed the major
      dependence on the interrogation window, and revealed less of a dependence on
      background features. BOS applied to shock-wave reflection from a wedge in a shock
      tube gave qualitative results, due to large uncertainties. But, the application
      to cooling by natural convection gave satisfactory results, comparable to
      thermocouple data and theory.

PMID- 23128703
TI  - Modeling the avalanche diode as a photon detector in quantum optical
      interferometers.
AB  - Avalanche diodes (ADs) are widely used to count photons in quantum
      interferometry. In reality they do not count photons, but click once when a bunch
      of photons arrives in a light pulse. We model this behavior in typical quantum
      optical interferometers like the Hong-Ou-Mandel beam splitter and the Mach
      Zehnder interferometer, and compare it with the behavior of the photon-number
      resolving (PNR) detector and the Hanbury-Brown-Twiss detector in these measuring
      devices. Our results show that quantum interferometric measurements with
      biphotons could be performed with single ADs, if the noise of the diodes could be
      reduced. Even a single PNR detector can be used in these interferometers, if the
      variance of the measurement is determined, since it reveals information about
      biphoton interference in contrast to the single detector counting rate.

PMID- 23128704
TI  - Image fusion through feature extraction by using sequentially combined toggle and
      top-hat based contrast operator.
AB  - Combing the useful information of multisensor or multifocus images is important
      for producing effective optical images. To extract and combine the image features
      of the original images for image fusion well, an algorithm through feature
      extraction by using the sequentially combined toggle and top-hat based contrast
      operator is proposed in this paper. Sequentially combining toggle contrast
      operator and top-hat based contrast operator could be used to identify well the
      effective bright and dark image features. Furthermore, through multiscale
      extension, the effective bright and dark image features at multiscales of an
      image are extracted. After the final bright and dark fusion features are
      constructed by using the pixel-wise maximum operation on the multiscale image
      features from different images, the final fusion result is obtained by importing
      the final bright and dark fusion features into the base image. Experimental
      results on different types of images show that the proposed algorithm performs
      well for image fusion, which may be widely used in different applications, such
      as security surveillance, object recognition, and so on.

PMID- 23128705
TI  - Intensity fluctuation spectra of dynamic laser speckle patterns acquired by a
      full-field temporal modulation method.
AB  - A method for obtaining the intensity fluctuation spectra of dynamic laser speckle
      patterns is introduced, which is based on the temporal modulation of the
      illumination and the subsequent integration of the intensity signals. This
      approach does not rely on the fast sampling rate to meet the Nyquist criterion,
      making it applicable for full-field imaging applications. The intensity
      fluctuation spectra created by the in-plane motion of a random phase object was
      investigated by using both a single-channel detector and a multichannel sensor.
      The power spectra obtained by using the full-field temporal modulation method
      were found to agree with the homodyne Doppler spectra obtained by using the
      method of autocorrelation and Fourier transform.

PMID- 23128706
TI  - Beam wander of electromagnetic Gaussian-Schell model beams propagating in
      atmospheric turbulence.
AB  - The general model of beam wander for a coherent Gaussian beam propagating through
      atmospheric turbulence is extended to the case of a partially polarized
      electromagnetic Gaussian-Schell model (EGSM) beam. The expression of the beam
      wander is obtained by characterizing the EGSM beam with the effective beam
      parameters. The effects of initial spatially coherent lengths, degree of
      polarization, and phase curvature are examined in detail. A condition is derived
      under which beams with different spatial coherence and degrees of polarization
      will generate the same beam wander.

PMID- 23128707
TI  - Heat generation in Nd:YAG at different doping levels.
AB  - Nd:YAG lasers with output power levels of tens of watts, a nearly diffraction
      limited beam quality, and a linearly polarized continuous wave output are
      commonly pumped by laser diodes at a wavelength around 808 nm, where the pump
      light spectrum is matched well to the absorption maximum of Nd:YAG. As a
      consequence, low Nd(3+)-doping concentrations of the laser crystals are required
      in order to minimize thermally induced stress. The use of higher Neodymium
      concentrations requires pump wavelengths beside the 808 nm absorption maximum and
      will furthermore result in changed thermo-optical behavior of the material. We
      present simulations and experimental results on how the doping concentration of
      Nd(3+) influences the fraction of pump light converted into heat.

PMID- 23128708
TI  - Experimental study of the influence of refraction on underwater three-dimensional
      reconstruction using the SVP camera model.
AB  - In an underwater imaging system, a perspective camera is often placed outside a
      tank or in waterproof housing with a flat glass window. The refraction of light
      occurs when a light ray passes through the water-glass and air-glass interface,
      rendering the conventional multiple view geometry based on the single viewpoint
      (SVP) camera model invalid. While most recent underwater vision studies mainly
      focus on the challenging topic of calibrating such systems, no previous work has
      systematically studied the influence of refraction on underwater three
      dimensional (3D) reconstruction. This paper demonstrates the possibility of using
      the SVP camera model in underwater 3D reconstruction through theoretical analysis
      of refractive distortion and simulations. Then, the performance of the SVP camera
      model in multiview underwater 3D reconstruction is quantitatively evaluated. The
      experimental results reveal a rather surprising and useful yet overlooked fact
      that the SVP camera model with radial distortion correction and focal length
      adjustment can compensate for refraction and achieve high accuracy in multiview
      underwater 3D reconstruction (within 0.7 mm for an object of dimension 200 mm)
      compared with the results of land-based systems. Such an observation justifies
      the use of the SVP camera model in underwater application for reconstructing
      reliable 3D scenes. Our results can be used to guide the selection of system
      parameters in the design of an underwater 3D imaging setup.

PMID- 23128709
TI  - Computational manufacturing as a key element in the design-production chain for
      modern multilayer coatings.
AB  - We propose a general approach that allows one to reveal factors causing
      production errors in the course of the deposition process controlled by broadband
      optical monitoring. We consider computational experiments simulating the real
      deposition process as a crucial point of this approach. We demonstrate
      application of the approach using multiple experimental deposition runs of the
      selected multilayer coatings.

PMID- 23128710
TI  - 3D shape reconstruction of large specular surface.
AB  - A novel three-dimensional (3D) reconstruction method based on fringe reflection
      technique for shape measurement of large specular surfaces is presented in this
      paper, which effectively integrates path integration technique with zonal
      wavefront reconstruction algorithm. The height information of specular surface
      obtained from cross-path integration can then be used as the initial value in a
      zonal wavefront reconstruction algorithm. This method not only has the advantages
      of global integration, but also enables user-friendly, high-speed operation. A
      specific iterative algorithm is adopted to improve the antinoise capability of
      the measuring system, which accelerates the rate of convergence significantly and
      even improves the accuracy of the reconstructed 3D surface. Moreover, the proper
      use of boundary contour extraction of the acquired images reduces the
      computational load of 3D reconstruction dramatically and hence achieves high
      reconstruction accuracy and enhances the surface integrity at the boundary. An
      ultraprecision, diamond-turned planar mirror with diameter of 150 mm has been
      employed to implement the system calibration. The reconstruction results of
      simulated and actual hyperbolic surfaces and the gauge blocks identify the
      validity of this new method. It is demonstrated that the measurement error is
      about 50 MUm with reconstruction points of 150*560 pixels of gauge blocks.

PMID- 23128711
TI  - Theoretical analysis for spherical aberration induction with low-order correction
      in refractive surgery: comment.
AB  - In this paper, we reply to post-surgical corneal asphericity conclusions made by
      Dai [Appl. Opt.51, 3966 (2012)]. We deduced, after a theoretical analysis, that
      the conclusions derived from this analysis are not theoretically or
      experimentally sound, because the author considers only the Munnerlyn formula for
      ablation algorithms and not the paraxial Munnerlyn formula, which is widespread
      in refractive surgery [J. Cataract Refract. Surg.14, 46 (1988)]. We refer to a
      previous paper published by Jimenez et al. [J. Opt. Soc. Am. A21, 98 (2004)] for
      a complete analysis on this matter that clarifies some points of confusion in
      Dai's paper.

PMID- 23128713
TI  - Focus tuning by liquid crystal lens in imaging system.
AB  - A quantitative study of the focus tuning by a liquid crystal lens in an imaging
      system composed of a camera module and the liquid crystal lens that performs the
      focusing function is reported. The resolving capability of the imaging system is
      investigated by analyzing the image of an ISO12233 chart formed by the system.
      Measurements show that with the focus tuning by the liquid crystal lens, the
      resolving power of the system can be very close to that of the camera module.

PMID- 23128714
TI  - Mid-infrared point sensor for in situ monitoring of CO2 emissions from large
      scale engines.
AB  - This paper describes an optical fiber based system that has been developed for
      the monitoring of carbon dioxide emissions in situ within engines above 500 kW.
      Conventional sensors, reviewed here, fail to meet monitoring requirements, such
      as lifespan, accuracy, and robustness. This paper describes a sensor designed as
      a single point reflective probe configuration using low cost, compact mid
      infrared optical components, making it suitable for insertion in large-scale
      engines including automotive tailpipes. The response of the sensor to carbon
      dioxide supplied from a cylinder in the laboratory environment is presented, as
      well as a number of experimental results taken in situ in an exhaust of an
      automotive diesel engine (smaller than 500 kW). The sensor is shown to have a
      long term stable operation over a wide range of concentrations (2%-15% CO(2))
      with a lower detection limit smaller than the lowest value encountered in modern
      day engines.

PMID- 23128715
TI  - Nanocomposite polyacrylamide based open cavity fiber Fabry-Perot humidity sensor.
AB  - A humidity sensor with a low temperature sensitivity is proposed and demonstrated
      by coating a nanocomposite hygrometer polyacrylamide in an open interferometric
      cavity of a fiber Fabry-Perot interferometer. In this paper the Fabry-Perot
      structure is formed by splicing one short section of single mode fiber between
      two sections of single mode fiber with a larger offset fusing method.
      Experimental results show that relative humidity (RH) sensitivity of the sensor
      is ~0.1 nm/(1% RH) in the range of 38% to 78% RH and ~5.868 nm/(1%RH) in the
      range of 88% to 98% RH, respectively.

PMID- 23128716
TI  - Optimization of two-glass monocentric lenses for compact panoramic imagers:
      general aberration analysis and specific designs.
AB  - Monocentric lenses have recently changed from primarily a historic curiosity to a
      potential solution for panoramic high-resolution imagers, where the spherical
      image surface is directly detected by curved image sensors or optically
      transferred onto multiple conventional flat focal planes. We compare imaging and
      waveguide-based transfer of the spherical image surface formed by the monocentric
      lens onto planar image sensors, showing that both approaches can make the system
      input aperture and resolution substantially independent of the input angle. We
      present aberration analysis that demonstrates that wide-field monocentric lenses
      can be focused by purely axial translation and describe a systematic design
      process to identify the best designs for two-glass symmetric monocentric lenses.
      Finally, we use this approach to design an F/1.7, 12 mm focal length imager with
      an up to 160 degrees  field of view and show that it compares favorably in size
      and performance to conventional wide-angle imagers.

PMID- 23128717
TI  - Energy distributions of electrons emitted from reflection-mode Cs-covered GaAs
      photocathodes.
AB  - By calculating the energy distributions of electrons reaching the photocathode
      surface and solving the Schrodinger equation for an electron tunneling through
      the surface potential barrier, we have obtained an equation to calculate the
      energy distributions of electrons emitted from reflection-mode Cs-covered GaAs
      photocathodes based on a two-minima diffusion model. According to the equation,
      we studied the effects of incident photon energies, diffusion lengths, and
      surface potential barrier on the electron energy distributions. The equation was
      also used to fit the measured electron energy distribution curves and the cathode
      performance parameters were obtained from the fitting. The Gamma and L peaks in
      the theoretical curves are in agreement with the peaks in the experimental
      curves. The fitted barrier thickness 1.7 A exactly reflects the GaAs-Cs dipole
      layer thickness.

PMID- 23128718
TI  - Target acquisition performance in a cluttered environment.
AB  - Most existing target acquisition (TA) models neglect the influence of background
      clutter, which results in inaccurate prediction of TA performance in a
      complicated environment. In this paper, all the background clutter is first
      quantitatively characterized by the distribution of edge clutter metric, and its
      effects on the target detection probability are analyzed. Further, a novel TA
      model is developed by combining this proposed clutter metric and the target task
      performance metric based on probability statistics theory. Moreover, this
      proposed model is validated by the search_2 dataset, and experiment results show
      that it is more consistent with the subjective detection probability than other
      models.

PMID- 23128719
TI  - Large deformation measurement using digital image correlation: a fully automated
      approach.
AB  - In digital image correlation, the iterative spatial domain cross-correlation
      algorithm is considered as a gold standard for matching the corresponding points
      in two images, but requires an accurate initial guess of the deformation
      parameters to converge correctly and rapidly. In this work, we present a fully
      automated method to accurately initialize all points of interest for the deformed
      images in the presence of large rotation and/or heterogeneous deformation. First,
      a robust computer vision technique is adopted to match feature points detected in
      reference and deformed images. The deformation parameters of the seed point are
      initialized from the affine transform, which is fitted to the matched feature
      points around it. Subsequently, the refined parameters are automatically
      transferred to adjacent points using a modified quality-guided initial guess
      propagation scheme. The proposed method not only ensures a rapid and correct
      convergence of the nonlinear optimization algorithm by providing a complete and
      accurate initial guess of deformation for each measurement point, but also
      effectively deals with deformed images with relatively large rotation and/or
      heterogeneous deformation. Tests on both simulated speckle images and real-world
      foam compression experiment verify the effectiveness and robustness of the
      proposed method.

PMID- 23128720
TI  - Near-field self-induced hollow spot through localized heating of
      polycarbonate/ZnS stack layer.
AB  - We have found an alternative way of achieving a doughnutlike focused spot by
      simply melting a subwavelength scatterer in a polycarbonate/ZnS sample. The near
      field microscopy technique is used to directly measure the induced doughnut spot
      in the near-field regime. A numerical model based on rigorous solution of the
      Maxwell's equations is proposed to study the phenomena. The simulations help to
      understand the optical mechanism behind the spot formation.

PMID- 23128721
TI  - Detection of an underwater target through modulated lidar experiments at grazing
      incidence in a deep wave basin.
AB  - The effectiveness of a pulsed radiofrequency modulated lidar and associated
      processing for underwater target detection at grazing incidence was
      experimentally assessed in a wave basin 50 m long and 20 m deep, under different
      conditions of swell produced within this facility to benefit from a controlled
      interface. This paper reports our experiments and offline data processing
      results, and describes significant improvements in the probability of detection
      that demonstrate the interest of using such a technique in this context.

PMID- 23128722
TI  - Background first- and second-order modeling for point target detection.
AB  - This paper deals with point target detection in nonstationary backgrounds such as
      cloud scenes in aerial or satellite imaging. We propose an original spatial
      detection method based on first- and second-order modeling (i.e., mean and
      covariance) of local background statistics. We first show that state-of-the-art
      nonlocal denoising methods can be adapted with minimal effort to yield edge
      preserving background mean estimates. These mean estimates lead to very efficient
      background suppression (BS) detection. However, we propose that BS be followed by
      a matched filter based on an estimate of the local spatial covariance matrix. The
      identification of these matrices derives from a robust classification of pixels
      in classes with homogeneous second-order statistics based on a Gaussian mixture
      model. The efficiency of the proposed approaches is demonstrated by evaluation on
      two cloudy sky background databases.

PMID- 23128723
TI  - Light-shift measurement and suppression in atomic spin gyroscope.
AB  - We present a method to determine and suppress the light shift in an atomic spin
      gyroscope. This method doesn't require additional drive source or frequency
      modulation, and it is based on the dynamics of an atomic spin gyroscope to
      determine a clean curve as a function of the frequency of the pump beam that
      predicts the zero light shift. We experimentally validate the method in a Cs
      (129)Xe atomic spin gyroscope and verify the results through numerical
      simulations. This method can also be applied to an atomic spin magnetometer based
      on the spin-exchange relaxation-free exchange that experiences light shift. The
      method is useful for atomic spin devices because it can improve long-term
      performance and reduce the influence of the laser.

PMID- 23128724
TI  - Arrayed waveguide grating interrogator for fiber Bragg grating sensors:
      measurement and simulation.
AB  - A fiber Bragg grating (FBG) interrogation system based on an intensity
      demodulation and demultiplexing of an arrayed waveguide grating (AWG) module is
      examined in detail. The influence of the spectral line shape of the FBG on the
      signal obtained from the AWG device is discussed by accomplishing the measurement
      and simulation of the system. The simulation of the system helps to create
      quickly and precisely calibration functions for nonsymmetric, tilted, or
      nonapodized FBGs. Experiments show that even small sidebands of nonapodized FBGs
      have strong influences on the signal resulted by an AWG device with a Gaussian
      profile.

PMID- 23128725
TI  - Three-dimensional shape measurement of a highly reflected, specular surface with
      structured light method.
AB  - This paper proposes a mathematical measurement model of a highly reflected,
      specular surface with structured light method. In the measurement, an auxiliary
      fringe pattern named amplitude perturbation is adopted to be projected onto the
      measured surface. The amplitude perturbation can ease the procedure of searching
      the corresponding points between the phase map of the measured surface and that
      of the reference plane by locking up the most reliable point as the starting
      unwrapping point whose true phase can be calculated accurately. The proposed
      method is also suitable for measuring the step surfaces such as gauge blocks with
      different heights. Furthermore, the image segmentation technology is introduced
      in the phase unwrapping procedure to increase the speed. Based on the unwrapped
      phase map, zonal wave-front reconstruction algorithm is implemented to realize
      three-dimensional, highly reflected, specular surface reconstruction.
      Experimental studies show that the developed methodology displays accuracy and
      high stability for highly reflected, specular surface measurement.

PMID- 23128726
TI  - Differential effects of high-temperature stress on nuclear topology and
      transcription of repetitive noncoding and coding rye sequences.
AB  - The plant stress response has been extensively characterized at the biochemical
      and physiological levels. However, knowledge concerning repetitive sequence
      genome fraction modulation during extreme temperature conditions is scarce. We
      studied high-temperature effects on subtelomeric repetitive sequences (pSc200)
      and 45S rDNA in rye seedlings submitted to 40 degrees C during 4 h. Chromatin
      organization patterns were evaluated through fluorescent in situ hybridization
      and transcription levels were assessed using quantitative real-time PCR.
      Additionally, the nucleolar dynamics were evaluated through fibrillarin
      immunodetection in interphase nuclei. The results obtained clearly demonstrated
      that the pSc200 sequence organization is not affected by high-temperature stress
      (HTS) and proved for the first time that this noncoding subtelomeric sequence is
      stably transcribed. Conversely, it was demonstrated that HTS treatment induces
      marked rDNA chromatin decondensation along with nucleolar enlargement and a
      significant increase in ribosomal gene transcription. The role of noncoding and
      coding repetitive rye sequences in the plant stress response that are suggested
      by their clearly distinct behaviors is discussed. While the heterochromatic
      conformation of pSc200 sequences seems to be involved in the stabilization of the
      interphase chromatin architecture under stress conditions, the dynamic modulation
      of nucleolar and rDNA topology and transcription suggest their role in plant
      stress response pathways.

PMID- 23128727
TI  - Evaluation of phosphorus indices after twenty years of science and development.
AB  - The P Index was proposed as a nutrient management tool in 1992 and has been
      implemented as such for the past decade. However, lack of water quality
      improvement in agricultural watersheds and discrepancies in P loss ratings
      between P indices have raised questions about continued use of the P Index. In
      response to these concerns, a symposium was held as part of the 2011 ASA, CSSA,
      SSSA annual meetings. This symposium produced a special collection of seven
      papers describing the role of P indices in P management, evaluation of P indices,
      new models for assessing P loss, methods to improve P indices, and changes in
      producer behavior resulting from P Index use. The objectives of this introductory
      paper are to provide background on the P Index concept, overviews of the special
      collection papers, and recommendations for future P Index evaluation and
      development research. The papers in this special collection conclude that P
      indices can provide accurate assessments of P loss but must be evaluated
      appropriately. Evaluation will require compiling large regional P loss datasets
      at field and small watershed scales. Simulation models may be used to generate P
      loss estimates; however, models must be calibrated and validated to ensure their
      accuracy. Further development of P indices will require coordinated regional
      efforts to identify common P Index frameworks and standardized interpretations.
      Stringent P Index evaluations will expand the utility of P indices for critical
      source area identification and strategic best management practice implementation
      by regulatory, education, and scientific communities alike.

PMID- 23128728
TI  - Phosphorus indices: why we need to take stock of how we are doing.
AB  - Many states have invested significant resources to identify components of their
      Phosphorus (P) Index that reliably estimate the relative risk of P loss and
      incentivize conservation management. However, differences in management
      recommendations and manure application guidelines for similar field conditions
      among state P Indices, coupled with minimal reductions in the extent of P
      impaired surface waters and soil test P (STP) levels, led the U.S. Natural
      Resources Conservation Service (NRCS) to revise the 590 Nutrient Management
      Standard. In preparation for this revision, NRCS requested that a review of the
      scientific underpinnings and accuracy of current P Indices be undertaken. They
      also sought to standardize the interpretation and management implications of P
      Indices, including establishment of ratings above which P applications should be
      curtailed. Although some states have initiated STP thresholds above which no
      application of P is allowed, STP alone cannot define a site's risk of P loss.
      Phosphorus Indices are intended to account for all of the major factors leading
      to P loss. A rigorous evaluation of P Indices is needed to determine if they are
      directionally and magnitudinally correct. Although use of observed P loss data
      under various management scenarios is ideal, such data are spatially and
      temporally limited. Alternatively, the use of a locally validated water quality
      model that has been shown to provide accurate estimates of P loss may be the most
      expedient option to conduct Index assessments in the short time required by the
      newly revised 590 Standard.

PMID- 23128729
TI  - Accounting for the risks of phosphorus losses through tile drains in a phosphorus
      index.
AB  - Tile drainage systems have been identified as a significant conduit for
      phosphorus (P) losses to surface water, but P indices do not currently account
      for this transport pathway in a meaningful way. Several P indices mention tile
      drains, but most account for either the reduction in surface runoff or the
      enhanced transport through tiles rather than both simultaneously. A summary of
      the current state of how tile drains are accounted for within P indices is
      provided, and the challenges in predicting the risk of P losses through tile
      drains that are relative to actual losses are discussed. A framework for a
      component P Index is described, along with a proposal to incorporate predictions
      of losses through tile drains as a component within this framework. Options for
      calibrating and testing this component are discussed.

PMID- 23128730
TI  - Testing the Wisconsin Phosphorus Index with year-round, field-scale runoff
      monitoring.
AB  - The Wisconsin Phosphorus Index (WPI) is one of several P indices in the United
      States that use equations to describe actual P loss processes. Although for
      nutrient management planning the WPI is reported as a dimensionless whole number,
      it is calculated as average annual dissolved P (DP) and particulate P (PP) mass
      delivered per unit area. The WPI calculations use soil P concentration, applied
      manure and fertilizer P, and estimates of average annual erosion and average
      annual runoff. We compared WPI estimated P losses to annual P loads measured in
      surface runoff from 86 field-years on crop fields and pastures. As the erosion
      and runoff generated by the weather in the monitoring years varied substantially
      from the average annual estimates used in the WPI, the WPI and measured loads
      were not well correlated. However, when measured runoff and erosion were used in
      the WPI field loss calculations, the WPI accurately estimated annual total P
      loads with a Nash-Sutcliffe Model Efficiency (NSE) of 0.87. The DP loss estimates
      were not as close to measured values (NSE = 0.40) as the PP loss estimates (NSE =
      0.89). Some errors in estimating DP losses may be unavoidable due to
      uncertainties in estimating on-farm manure P application rates. The WPI is
      sensitive to field management that affects its erosion and runoff estimates.
      Provided that the WPI methods for estimating average annual erosion and runoff
      are accurately reflecting the effects of management, the WPI is an accurate field
      level assessment tool for managing runoff P losses.

PMID- 23128731
TI  - Comparing phosphorus indices from twelve southern U.S. states against monitored
      phosphorus loads from six prior southern studies.
AB  - Forty-eight states in the United States use phosphorus (P) indices to meet the
      requirements of their Natural Resources Conservation Service (NRCS) Code 590
      Standard, which provides national guidance for nutrient management of
      agricultural lands. The majority of states developed these indices without
      consultation or coordination with neighboring states to meet specific local
      conditions and policy needs. Using water quality and land treatment data from six
      previously published articles, we compared P loads with P-Index values and
      ratings using the 12 southern P indices. When total measured P loads were
      regressed with P-Index rating values, moderate to very strong relationships (0.50
      to 0.97) existed for five indices (Arkansas, Florida, Georgia, North Carolina,
      and South Carolina) and all but one index was directionally correct. Regressions
      with dissolved P were also moderate to very strong ( of 0.55 to 0.95) for the
      same five state P indices (Arkansas, Florida, Georgia, North Carolina, and South
      Carolina); directionality of the Alabama Index was negative. When total measured
      P loads were transformed to current NRCS 590 Standard ratings (Low [<2.2 kg P
      ha], Moderate, [2.2-5.5 kg P ha], and High [>5.5 kg P ha]) and these ratings were
      then compared to the southern-Index ratings, many of the P indices correctly
      identified Low losses (77%), but most did not correctly identify Moderate or High
      loss situations (14 and 31%, respectively). This study demonstrates that while
      many of the P indices were directionally correct relative to the measured water
      quality data, there is a large variability among southern P indices that may
      result in different P management strategies being employed under similar
      conditions.

PMID- 23128732
TI  - Simulating soil phosphorus dynamics for a phosphorus loss quantification tool.
AB  - Pollution of fresh waters by agricultural phosphorus (P) is a water quality
      concern. Because soils can contribute significantly to P loss in runoff, it is
      important to assess how management affects soil P status over time, which is
      often done with models. Our objective was to describe and validate soil P
      dynamics in the Annual P Loss Estimator (APLE) model. APLE is a user-friendly
      spreadsheet model that simulates P loss in runoff and soil P dynamics over 10 yr
      for a given set of runoff, erosion, and management conditions. For soil P
      dynamics, APLE simulates two layers in the topsoil, each with three inorganic P
      pools and one organic P pool. It simulates P additions to soil from manure and
      fertilizer, distribution among pools, mixing between layers due to tillage and
      bioturbation, leaching between and out of layers, crop P removal, and loss by
      surface runoff and erosion. We used soil P data from 25 published studies to
      validate APLE's soil P processes. Our results show that APLE reliably simulated
      soil P dynamics for a wide range of soil properties, soil depths, P application
      sources and rates, durations, soil P contents, and management practices. We
      validated APLE specifically for situations where soil P was increasing from
      excessive P inputs, where soil P was decreasing due to greater outputs than
      inputs, and where soil P stratification occurred in no-till and pasture soils.
      Successful simulations demonstrate APLE's potential to be applied to major
      management scenarios related to soil P loss in runoff and erosion.

PMID- 23128733
TI  - Using a phosphorus loss model to evaluate and improve phosphorus indices.
AB  - In most states, the phosphorus (P) index (PI) is the adopted strategy for
      assessing a field's vulnerability to P loss; however, many state PIs have not
      been rigorously evaluated against measured P loss data to determine how well the
      PI assigns P loss risk-a major reason being the lack of field data available for
      such an analysis. Given the lack of P loss data available for PI evaluation, our
      goal was to demonstrate how a P loss model can be used to evaluate and revise a
      PI using the Pennsylvania (PA) PI as an example. Our first objective was to
      compare two different formulations-multiplicative and component-for calculating a
      PI. Our second objective was to evaluate whether output from a P loss model can
      be used to improve PI weighting by calculating weights for modified versions of
      the PA PI from model-generated P loss data. Our results indicate that several
      potential limitations exist with the original multiplicative index formulation
      and that a component formulation is more consistent with how P loss is calculated
      with P loss models and generally provides more accurate estimates of P loss.
      Moreover, using the PI weights calculated from the model-generated data
      noticeably improved the correlation between PI values and a large and diverse
      measured P loss data set. The approach we use here can be used with any P loss
      model and PI and thus can serve as a guide to assist states in evaluating and
      modifying their PI.

PMID- 23128734
TI  - Phosphorus index as a phosphorus awareness tool: documented phosphorus use
      reduction in New York state.
AB  - In 1999, New York introduced its concentrated animal feeding operation (CAFO)
      permit followed, in 2001, by release of the New York phosphorus index (NY-PI) and
      establishment of a statewide on-farm research partnership. State policy requires
      that the Natural Resources Conservation Service's 590 nutrient management
      standard, and therefore the NY-PI, be implemented on all CAFO farms as well as
      animal feeding operations (AFOs) receiving state or federal cost share funds for
      manure storage and other related practices. Since the introduction of the NY-PI,
      P fertilizer sales (farm use) declined from 14,470 Mg in 2001 (8.6 kg P ha) to
      7,376 Mg in 2009 (5.0 kg P ha). Cost of fertilizer was not a significant
      covariate for the reduction in P use over time. Certified nutrient management
      planners were surveyed in 2011 to evaluate their perceptions of drivers for
      changes in P use. In addition, whole farm P balances were recorded for 54 New
      York dairy farms. The survey data illustrate key ingredients for success: (i)
      statewide awareness of environmental challenges through both regulations and
      extension programming; (ii) science-based, user-friendly tools that allow for
      farm-specific responses to the challenges; (iii) risk assessment of management
      alternatives through on-farm research; (iv) enforcement of regulations; and (v)
      existence of economically feasible alternatives. Whole farm balances showed a
      reduction in P surplus of 44%, averaged across farms, whereas milk production
      increased, further illustrating the willingness and economic potential to make
      changes that improve production efficiency and reduce risk of nutrient loss to
      the environment.

PMID- 23128735
TI  - Soil greenhouse gas emissions affected by irrigation, tillage, crop rotation, and
      nitrogen fertilization.
AB  - Management practices, such as irrigation, tillage, cropping system, and N
      fertilization, may influence soil greenhouse gas (GHG) emissions. We quantified
      the effects of irrigation, tillage, crop rotation, and N fertilization on soil
      CO, NO, and CH emissions from March to November, 2008 to 2011 in a Lihen sandy
      loam in western North Dakota. Treatments were two irrigation practices (irrigated
      and nonirrigated) and five cropping systems (conventional-tilled malt barley [
      L.] with N fertilizer [CT-N], conventional-tilled malt barley with no N
      fertilizer [CT-C], no-tilled malt barley-pea [ L.] with N fertilizer [NT-PN], no
      tilled malt barley with N fertilizer [NT-N], and no-tilled malt barley with no N
      fertilizer [NT-C]). The GHG fluxes varied with date of sampling and peaked
      immediately after precipitation, irrigation, and/or N fertilization events during
      increased soil temperature. Both CO and NO fluxes were greater in CT-N under the
      irrigated condition, but CH uptake was greater in NT-PN under the nonirrigated
      condition than in other treatments. Although tillage and N fertilization
      increased CO and NO fluxes by 8 to 30%, N fertilization and monocropping reduced
      CH uptake by 39 to 40%. The NT-PN, regardless of irrigation, might mitigate GHG
      emissions by reducing CO and NO emissions and increasing CH uptake relative to
      other treatments. To account for global warming potential for such a practice,
      information on productions associated with CO emissions along with NO and CH
      fluxes is needed.

PMID- 23128736
TI  - Optimization of biomixture composition and water management for maximum pesticide
      dissipation in peat-free biobeds.
AB  - Biomixture composition and water management are key factors controlling biobeds
      performance. Although compost-biomixtures (BXs) possess high degradation
      efficiency, their low water-holding capacity compared with peat-biomixtures (OBX)
      limits their use. Thus, appropriate water management is required to optimize
      their performance. The dissipation capacity of selected BXs compared with OBXs
      was assessed in a column study under two water managements not differing in their
      total water load but in the intensity and frequency of water addition. Results
      showed that the less frequent application of large water volumes (water
      management scenario I) facilitated pesticide leaching (0.001-10.4% of initially
      applied), compared with the frequent application of low water volumes (water
      management scenario II) where leaching losses were always <1%. Water management
      affected differently the dissipation performance of substrates: OBX outperformed
      BXs under water management scenario I, whereas the grape marc compost-biomixture
      (BX1) was superior at water management scenario II. Substitution of grape marc
      compost (C1) with olive leaves compost (C2) or of straw with corn cobs or grape
      stalks reduced the dissipation capacity of BX1. Mass balance analysis revealed
      that the high dissipation capacity of OBX was mostly attributable to its high
      ability to retain rather than degrade pesticides, whereas the exact opposite was
      seen for BX1. Overall, our findings suggest that BXs-biobeds could treat large
      wastewater volumes under appropriate water management that extends the contact
      period between pesticides and BXs, thus exploiting their high biodegradation
      capacity.

PMID- 23128737
TI  - A conceptual evaluation of sustainable variable-rate agricultural residue
      removal.
AB  - Agricultural residues have near-term potential as a feedstock for bioenergy
      production, but their removal must be managed carefully to maintain soil health
      and productivity. Recent studies have shown that subfield scale variability in
      soil properties (e.g., slope, texture, and organic matter content) that affect
      grain yield significantly affect the amount of residue that can be sustainably
      removed from different areas within a single field. This modeling study examines
      the concept of variable-rate residue removal equipment that would be capable of
      on-the-fly residue removal rate adjustments ranging from 0 to 80%. Thirteen
      residue removal rates (0% and 25-80% in 5% increments) were simulated using a
      subfield scale integrated modeling framework that evaluates residue removal
      sustainability considering wind erosion, water erosion, and soil carbon
      constraints. Three Iowa fields with diverse soil, slope, and grain yield
      characteristics were examined and showed sustainable, variable-rate agricultural
      residue removal that averaged 2.35, 7.69, and 5.62 Mg ha, respectively. In
      contrast, the projected sustainable removal rates using rake and bale removal for
      the entire field averaged 0.0, 6.40, and 5.06 Mg ha, respectively. The modeling
      procedure also projected that variable-rate residue harvest would result in 100%
      of the land area in all three fields being managed in a sustainable manner,
      whereas Field 1 could not be sustainably managed using rake and bale removal, and
      only 83 and 62% of the land area in Fields 2 and 3 would be managed sustainably
      using a rake and bale operation for the entire field. In addition, it was found
      that residue removal adjustments of 40 to 65% are sufficient to collect 90% of
      the sustainably available agricultural residue.

PMID- 23128738
TI  - Spatio-temporal variability of groundwater nitrate concentration in Texas: 1960
      to 2010.
AB  - Nitrate (NO) is a major contaminant and threat to groundwater quality in Texas.
      High-NO groundwater used for irrigation and domestic purposes has serious
      environmental and health implications. The objective of this study was to
      evaluate spatio-temporal trends in groundwater NO concentrations in Texas on a
      county basis from 1960 to 2010 with special emphasis on the Texas Rolling Plains
      (TRP) using the Texas Water Development Board's groundwater quality database.
      Results indicated that groundwater NO concentrations have significantly increased
      in several counties since the 1960s. In 25 counties, >30% of the observations
      exceeded the maximum contamination level (MCL) for NO (44 mg L NO) in the 2000s
      as compared with eight counties in the 1960s. In Haskell and Knox Counties of the
      TRP, all observations exceeded the NO MCL in the 2000s. A distinct spatial
      clustering of high-NO counties has become increasingly apparent with time in the
      TRP, as indicated by different spatial indices. County median NO concentrations
      in the TRP region were positively correlated with county-based area estimates of
      crop lands, fertilized croplands, and irrigated croplands, suggesting a negative
      impact of agricultural practices on groundwater NO concentrations. The highly
      transmissive geologic and soil media in the TRP have likely facilitated NO
      movement and groundwater contamination in this region. A major hindrance in
      evaluating groundwater NO concentrations was the lack of adequate recent
      observations. Overall, the results indicated a substantial deterioration of
      groundwater quality by NO across the state due to agricultural activities,
      emphasizing the need for a more frequent and spatially intensive groundwater
      sampling.

PMID- 23128739
TI  - Major element, trace element, nutrient, and radionuclide mobility in a mining by
      product-amended soil.
AB  - This study investigates the use of a mineral processing by-product, neutralized
      used acid (NUA), primarily composed of gypsum and Fe-oxyhydroxide, as a soil
      amendment. A 1489-d turf farm field trial assessed nutrient, trace element, and
      radionuclide mobility of a soil amended with ~5% by mass to a depth of 15 cm of
      NUA. Average PO-P fluxes collected as subsoil leachates were 0.7 and 26.6 kg ha
      yr for NUA-amended and control sites, respectively, equating to a 97% reduction
      in PO-P loss after 434 kg P ha was applied. Total nitrogen fluxes in NUA-amended
      soil leachates were similarly reduced by 82%. Incorporation of NUA conferred
      major changes in leachate geochemistry with a diverse suite of trace elements
      depleted within NUA-amended leachates. Gypsum dissolution from NUA resulted in an
      increase from under- to oversaturation of the soil leachates for a range of Fe-
      and Ca-minerals including calcite and ferrihydrite, many of which have a well
      documented ability to assimilate PO-P and trace elements. Isotopic analysis
      indicated little Pb addition from NUA. Both Sr and Nd isotope results revealed
      that NUA and added fertilizer became an important source of Ca to leachate and
      turf biomass. The NUA-amended soils retained a range of U-Th series
      radionuclides, with little evidence of transfer to soil leachate or turf biomass.
      Calculated radioactivity dose rates indicate only a small increment due to NUA
      amendment. With increased nutrient, trace element, and solute retention, and
      increased productivity, a range of potential agronomic benefits may be conferred
      by NUA amendment of soils, in addition to the potential to limit offsite nutrient
      loss and eutrophication.

PMID- 23128740
TI  - Hydrogeochemistry and isotopic tracing of nitrate contamination of two aquifer
      systems on Jeju Island, Korea.
AB  - The groundwater of Jeju Island (Republic of Korea) is vulnerable to contamination
      because its aquifers are mainly composed of highly permeable geological units and
      its agricultural fields are often exposed to excessive use of predominantly
      synthetic fertilizers. In the Gosan area of Jeju Island, we investigated nitrate
      contamination in both a perched aquifer above an impermeable clay bed and the
      regional groundwater beneath this aquitard. The deltaO and deltaD values indicate
      that the perched groundwater is recharged by local precipitation, whereas the
      regional groundwater is recharged mainly by regional flow from an adjacent
      mountainous region. The perched groundwater contained very high NO-N
      concentrations of up to 87 mg/L. The isotopic composition of nitrate in the
      perched groundwater showed that synthetic fertilizers applied in high excesses of
      crop N needs were the main cause of aquifer pollution. Elevated nitrate
      concentrations were also observed in the regional groundwater especially after
      precipitation events. Concentration and isotopic data revealed that the inflow of
      shallow perched groundwater along the poorly cemented or uncemented annulus of
      regional groundwater wells was one of the main reasons for the nitrate
      contamination observed in the regional groundwater. In both aquifers, deltaN and
      deltaO values showed that the sources of nitrate were derived from synthetic
      fertilizers that had been recycled in the soil zone by nitrification and in some
      portions of the perched aquifer (dissolved oxygen concentrations <2 mg/L)
      indicated that denitrification occurred locally.

PMID- 23128741
TI  - Trace elements in feed, manure, and manured soils.
AB  - Modern animal feeds often include nutritional mineral supplements, especially
      elements such as Cu, P, Se, and Zn. Other sources of trace elements also occur in
      livestock systems, such as pharmaceutical use of As and Zn to control gut flora,
      Bi in dairy for mastitis control, and Cu as hoof dips. Additionally, potential
      exists for inadvertent inclusion of trace elements in feeds or manures. There is
      concern about long-term accumulation of trace elements in manured soil that may
      even exceed guideline "safe" concentrations. This project measured ~60 elements
      in 124 manure samples from broiler, layer, turkey, swine grower, swine nursery,
      sow, dairy, and beef operations. The corresponding feeds were also analyzed. In
      general, concentrations in manure were two- to fivefold higher than those in
      feed: the manure/feed concentration ratios were relatively consistent for all the
      animal-essential elements and were numerically similar for many of the non
      nutrient elements. To confirm the potential for accumulation in soil, total trace
      element concentrations were measured in the profiles of 10 manured and 10
      adjacent unmanured soils. Concentrations of several elements were found to be
      elevated in the manured soils, with Zn (and P) the most common. One soil from a
      dairy standing yard had concentrations of B that exceeded soil health guideline
      concentrations. Given that the Cu/P and Zn/P ratios found in manure were greater
      than typically reported in harvested crop materials, these elements will
      accumulate in soil even if manure application rates are managed to prevent
      accumulation of P in soil.

PMID- 23128742
TI  - Biosulfides precipitation in weathered tailings amended with food waste-based
      compost and zeolite.
AB  - Tailings are mine wastes in the form of slurries stacked in mine sites abandoned
      after the exhaustion of ores. There are approximately 5000 abandoned mine sites
      in Korea, and tailings have become a serious environmental problem. Long-term
      environmental exposure of tailings can cause release of acidic and high
      concentrations of sulfate- and metal-contaminated water (acid mine drainage,
      AMD). Organic and/or inorganic amendments have been studied for AMD prevention
      and passive in situ treatment of pore water. This study tests locally available
      food waste-based compost as a viable amendment, in addition to the need for
      sustainable ways to dispose of compost, in response to a new environmental law.
      To examine the feasibility, three bioreactors were constructed, filled with
      mixtures of tailings, food waste-based compost, and zeolite. During the 4-wk
      experimental period, feeding water ormedium were poured in one reactor. The
      leachates were investigated in terms of chemistry and microbiology. Compared with
      the unamended reactor, the leachate from two mixture-filled reactors showed
      increased pH, formation of sulfate reduction conditions, and highly efficient
      metal removal. Black-colored precipitates observed at the end of the experiment
      suggested the formation of metal biosulfides, following the activity of sulfate
      reduction mediated by sulfate-reducing bacteria (SRB). Mineralogical analysis of
      these precipitates confirmed the presence of biosulfides, mainly of Fe and Pb.
      Moreover, microbial and molecular biological analyses revealed that several
      species of heterotrophic bacteria (SRB and iron-reducing bacteria) were present
      in the solids recovered from the bioreactors. Microbial consortium, such as SRB
      species (), and cellulosic-degrader ( sp.) were identified. This study provides
      promising results on the application potential of food waste-based compost for
      prevention of AMD generation and passive in situ treatment of pore water in
      weathered tailings in Korea and elsewhere.

PMID- 23128743
TI  - Zinc speciation in proximity to phosphate application points in a lead/zinc
      smelter-contaminated soil.
AB  - The use of P to immobilize Pb in contaminated soils has been well documented.
      However, the influence of P on Zn speciation in soils has not been extensively
      examined, and these two metals often occur as co-contaminants. We hypothesized
      that additions of P to a Pb/Zn-contaminated soil would induce Zn phosphate
      mineral formation and fluid P sources would be more effective than granular P
      amendments. A combination of different synchrotron-based techniques, namely,
      spatially resolved micro-X-ray fluorescence (MU-XRF), micro-extended X-ray
      absorption fine structure spectroscopy (MU-EXAFS), and micro-X-ray diffraction
      (MU-XRD), were used to speciate Zn at two incubation times in the proximity of
      application points (0 to 4 mm) for fluid and granular P amendments in a Pb/Zn
      smelter-contaminated soil. Phosphate rock (PR), triple super phosphate (TSP),
      monoammonium phosphate (MAP), and fluid ammonium polyphosphate induced Zn
      phosphate formation. Ammonium polyphosphate was more effective at greater
      distances (up to 3.7 mm) from the point of P application. Phosphoric acid
      increased the presence of soluble Zn species because of increased acidity.
      Soluble Zn has implications with respect to Zn bioavailability, which may
      negatively impact vegetation and other sensitive organisms. Although additions of
      P immobilize Pb, this practice needs close monitoring due to potential increases
      in Zn solubility in a Pb/Zn smelter-contaminated soil.

PMID- 23128744
TI  - Concentrations, loads, and yields of organic carbon in streams of agricultural
      watersheds.
AB  - Carbon is cycled to and from large reservoirs in the atmosphere, on land, and in
      the ocean. Movement of organic carbon from the terrestrial reservoir to the ocean
      plays an important role in the global cycling of carbon. The transition from
      natural to agricultural vegetation can change the storage and movement of organic
      carbon in and from a watershed. Samples were collected from 13 streams located in
      hydrologically and agriculturally diverse watersheds, to better understand the
      variability in the concentrations and loads of dissolved organic carbon (DOC) and
      particulate organic carbon (POC) in the streams, and the variability in watershed
      yields. The overall annual median concentrations of DOC and POC were 4.9 (range:
      2.1-6.8) and 1.1 (range: 0.4-3.8) mg C L, respectively. The mean DOC watershed
      yield (+/- SE) was 25 +/- 6.8 kg C ha yr. The yields of DOC from these
      agricultural watersheds were not substantially different than the DOC yield from
      naturally vegetated watersheds in equivalent biomes, but were at the low end of
      the range for most biomes. Total organic carbon (DOC + POC) annually exported
      from the agricultural watersheds was found to average 0.03% of the organic carbon
      that is contained in the labile plant matter and top 1 m of soil in the
      watershed. Since the total organic carbon exported from agricultural watersheds
      is a relatively small portion of the sequestered carbon within the watershed,
      there is the great potential to store additional carbon in plants and soils of
      the watershed, offsetting some anthropogenic CO emissions.

PMID- 23128745
TI  - Degradation and leaching of fluroxypyr after application to railway tracks.
AB  - Fluroxypyr is an auxin-type herbicide used for postemergent control of broad
      leaved weeds in agriculture and in nonagricultural environments such as railways.
      The overall aim of this study was to assess the potential environmental impact
      from fluroxypyr application to railway tracks and to elucidate some of the
      factors that control its environmental fate. In laboratory studies, we examined
      the degradation of fluroxypyr and the formation of its metabolites fluroxypyr
      methoxypyridine (F-MP) and fluroxypyr-pyridinol (F-P) in soil from two Swedish
      railways. We also investigated the degradation and leaching of fluroxypyr in
      three different railway plots treated with fluroxypyr (360 g ae ha). The half
      life of fluroxypyr in soil samples ranged between 28 and 78 d. An estimated mean
      48.6 +/- 20% of the fluroxypyr was converted into F-P and 8.0 +/- 2% into F-MP.
      The main metabolite, F-P, was rapidly degraded, with an average half-life of 10
      +/- 5 d. However, F-MP was not degraded to a significant degree in any sample,
      resulting in slowly increasing concentrations throughout the experiment. This
      pattern of relatively rapid degradation of F-P and slow accumulation of F-MP was
      also observed in the field. The persistent nature of F-MP may be of concern if
      fluroxypyr is used repeatedly at the same location. Fluroxypyr was detected in
      the groundwater beneath the track at all three locations studied in
      concentrations exceeding the EU limit of 0.1 MUg L for pesticides in drinking
      water, and F-P was detected in the groundwater at two of three locations. The
      most important factor controlling fluroxypyr degradation rate in soil was the
      soil water content, which modulated microbial activity and presumably also
      fluroxypyr availability to microorganisms. Our findings imply that fluroxypyr may
      not be a suitable herbicide for weed control on railway tracks.

PMID- 23128746
TI  - Analyzing the spatial distribution of PCB concentrations in soils using below
      quantification limit data.
AB  - Polychlorinated biphenyls (PCBs) are highly toxic environmental pollutants that
      can accumulate in soils. We consider the problem of explaining and mapping the
      spatial distribution of PCBs using a spatial data set of 105 PCB-187 measurements
      from a region in the north of France. A large proportion of our data (35%) fell
      below a quantification limit (QL), meaning that their concentrations could not be
      determined to a sufficient degree of precision. Where a measurement fell below
      this QL, the inequality information was all that we were presented with. In this
      work, we demonstrate a full geostatistical analysis-bringing together the various
      components, including model selection, cross-validation, and mapping-using
      censored data to represent the uncertainty that results from below-QL
      observations. We implement a Monte Carlo maximum likelihood approach to estimate
      the geostatistical model parameters. To select the best set of explanatory
      variables for explaining and mapping the spatial distribution of PCB-187
      concentrations, we apply the Akaike Information Criterion (AIC). The AIC provides
      a trade-off between the goodness-of-fit of a model and its complexity (i.e., the
      number of covariates). We then use the best set of explanatory variables to help
      interpolate the measurements via a Bayesian approach, and produce maps of the
      predictions. We calculate predictions of the probability of exceeding a
      concentration threshold, above which the land could be considered as
      contaminated. The work demonstrates some differences between approaches based on
      censored data and on imputed data (in which the below-QL data are replaced by a
      value of half of the QL). Cross-validation results demonstrate better predictions
      based on the censored data approach, and we should therefore have confidence in
      the information provided by predictions from this method.

PMID- 23128747
TI  - Competitive sorption of metsulfuron-methyl and tetracycline on corn straw
      biochars.
AB  - The application of biochars into soil may influence the fate of contaminants.
      Sorption and competitive sorption of metsulfuron-methyl (ME) and tetracycline
      (TC) on corn straw biochars prepared at 100 to 600 degrees C (referred to as
      CS100-CS600) were examined. The Freundlich model described sorption isotherms
      well. The lower sorption capacity () of ME compared with TC on the biochars was
      attributed to the electrostatic repulsion between the anionic ME and the
      negatively charged biochars. No electrostatic repulsion between the zwitterionic
      TC and the biochars occurred. Tetracycline exhibited little competition with ME
      for CS100-CS300 in bi-solute systems, suggesting that partitioning of ME into
      noncarbonized rubbery organic matter might be the dominant sorption mechanism.
      The nonlinear isotherms of ME on CS400-CS600 and those of TC on CS100-CS600
      suggested adsorption as the dominant mechanism. A significant increase in the
      Freundlich  values in the bi-solute systems might be attributed to TC/ME
      occupying and blocking ME/TC-specific adsorption sites. The percentage decreases
      in  of TC on CS400-CS600 with low ME concentrations were lower than those on
      CS200-CS300. This might be attributed to the lower steric restriction of ME for
      TC on CS400-CS600 because of their larger specific surface areas. The larger
      percentage decrease in  of ME with TC from CS400 to CS600 may be explained by a
      decrease in the hydrophobicity and the increased sorption of TC with numerous
      polar groups. When using biochars as engineered sorbents to prevent the transport
      of ME from soil, the effect of coexisting TC needs to be taken into account.

PMID- 23128748
TI  - Stabilization of enzymatically polymerized phenolic chemicals in a model soil
      organic matter-free geomaterial.
AB  - A variety of remediation methods, including contaminant transformation by
      peroxidase-mediated oxidative polymerization, have been proposed to manage soils
      and groundwater contaminated with chlorinated phenols. Phenol stabilization has
      been successfully observed during cross polymerization between phenolic polymers
      and soil organic matter (SOM) for soils with SOM >3%. This study evaluates
      peroxidase-mediated transformation and removal of 2,4-dichlorophenol (DCP) from
      an aqueous phase in contact with a natural geomaterial modified to contain
      negligible (<0.3%) SOM. The results are compared with those for soils with higher
      SOM. The SOM-free sorbent was generated by removing SOM using a NaOCl oxidation.
      When horseradish peroxidase (HRP) was used to induce polymerization of DCP, the
      soil-water phase distribution relationship (PDR) of DCP polymerization products
      (DPP) was complete within 1 d and PDRs did not significantly change over the 28 d
      of study. The conversion of DCP to DPP was close to 95% efficient. Extractable
      solute consisted entirely of DPP with 5% or less of unreacted DCP. The aqueous
      extractability of DPP from SOM-free geomaterial decreased at longer contact times
      and at smaller residual aqueous concentrations of DPP. DCP stabilization appeared
      to have resulted from a combination of sorption, precipitation, and ligand
      exchange between oligomeric products and the exposed mineral surfaces.
      Modification of the mineral surface through coverage with DPP enhanced the time
      dependent retention of the oligomers. DPP stabilization in SOM-free geomaterial
      was comparable with that reported in the literature with soil containing SOM
      contents >1%. Results from this study suggest that the effectiveness of HRP
      mediated stabilization of phenolic compounds not only depends on the cross
      coupling with SOM, but also on the modification of the surface of the sorbent
      that can augment affinity with oligomers and enhance stabilization. Coverage of
      the mineral surface by phenolic oligomers may be analogous to SOM that can
      potentially sorb other xenobiotics. HRP- mediated reactions can be used to
      stabilize DCP associated with low SOM mineral soils or aquifer media, thereby
      restricting the transport of phenolic contaminants in the soil environment.

PMID- 23128749
TI  - 17-beta estradiol and testosterone mineralization and incorporation into organic
      matter in broiler litter-amended soils.
AB  - The presence of the hormones estradiol and testosterone in the environment is of
      concern because they adversely affect vertebrate sexual characteristics. Land
      spreading broiler litter introduces these hormones into the environment. We
      conducted two studies. The first study determined the mineralization of C-labeled
      estradiol and testosterone at three water potentials and three temperatures in
      four broiler litter-amended soils. With a few exceptions, the mineralization of
      each hormone either stayed the same or increased with increasing water content
      (both hormones) and increasing (estradiol) or decreasing (testosterone)
      temperature. Mineralization was dependent on soil type. The second study
      determined the incorporation of C-labeled estradiol and testosterone into (i)
      three soil organic matter (SOM) fractions (fulvic acid, humic acid, and humin) at
      two water potentials, two temperatures, and one sampling time, and (ii) at one
      water potential, one temperature, and seven sampling times. As time increased,
      higher temperature and water potential decreased percentages of C estradiol and
      testosterone in water- and acetone-soluble fractions and increased percentages in
      SOM fractions. However, the distribution of the two hormones in SOM fractions
      differed. For estradiol, higher temperature and water potential increased the
      percentage in all three SOM fractions. For testosterone, higher temperature and
      water potential increased the percentage of hormone in fulvic acid and humin.
      Although the mineralization studies suggest the potential for these hormones to
      still have environmental effects, the incorporation of the two hormones into SOM
      suggest that land spreading these hormones may actually be less of an
      environmental concern.

PMID- 23128750
TI  - Effect of elevated carbon dioxide concentration on carbon assimilation under
      fluctuating light.
AB  - Natural fluctuations in light intensity may significantly affect the amount of CO
      assimilated by plants and ecosystems. Little is known, however, about the
      interactive effect of dynamic light conditions and atmospheric CO concentrations.
      The hypothesis that elevated CO concentration (EC; 700 MUmol CO mol) increases
      photosynthetic efficiency in dynamic light environments as compared to ambient CO
      concentration (AC; 385 MUmol CO mol) was tested. Sun leaves of European beech (
      L.) and current-year shoots of Norway spruce [ (L). Karst.] were exposed to five
      dynamic light regimes (LRs) occurring within forest canopies due to variable
      cloud cover or self-shading of leaves and to a steady-state LR. The LRs differed
      in the time course of incident irradiance, whereas the overall duration (600 s)
      and total amount of radiation (35.88 mmol photons m) were the same in all LRs.
      The EC treatment enhanced the amount of CO assimilated under all LRs tested.
      While the stimulation was only 37 to 50% in beech, it was 52 to 85% in spruce.
      The hypothesis that photosynthetic efficiency is stimulated by EC was confirmed
      in LRs when the leaves were pre-exposed to low light intensity and photosynthetic
      induction was required. By contrast, only a minor effect of EC treatment was
      found on the rate of induction loss and postillumination CO fixation in both
      species studied.

PMID- 23128751
TI  - Relating management practices and nutrient export in agricultural watersheds of
      the United States.
AB  - Relations between riverine export (load) of total nitrogen (N) and total
      phosphorus (P) from 133 large agricultural watersheds in the United States and
      factors affecting nutrient transport were evaluated using empirical regression
      models. After controlling for anthropogenic inputs and other landscape factors
      affecting nutrient transport-such as runoff, precipitation, slope, number of
      reservoirs, irrigated area, and area with subsurface tile drains-the relations
      between export and the area in the Conservation Reserve Program (CRP) (N) and
      conservation tillage (P) were positive. Additional interaction terms indicated
      that the relations between export and the area in conservation tillage (N) and
      the CRP (P) progressed from being clearly positive when soil erodibility was low
      or moderate, to being close to zero when soil erodibility was higher, to possibly
      being slightly negative only at the 90th to 95th percentile of soil erodibility
      values. Possible explanations for the increase in nutrient export with increased
      area in management practices include greater transport of soluble nutrients from
      areas in conservation tillage; lagged response of stream quality to
      implementation of management practices because of nitrogen transport in
      groundwater, time for vegetative cover to mature, and/or prior accumulation of P
      in soils; or limitations in the management practice and stream monitoring data
      sets. If lags are occurring, current nutrient export from agricultural watersheds
      may still be reflecting the influence of agricultural land-use practices that
      were in place before the implementation of these management practices.

PMID- 23128752
TI  - Bioretention column study of bacteria community response to salt-enriched
      artificial stormwater.
AB  - Cold climate cities with green infrastructure depend on soil bacteria to remove
      nutrients from road salt-enriched stormwater. Our research examined how bacterial
      communities in laboratory columns containing bioretention media responded to
      varying concentrations of salt exposure from artificial stormwater and the effect
      of bacteria and salt on column effluent concentrations. We used a factorial
      design with two bacteria treatments (sterile, nonsterile) and three salt
      concentrations (935, 315, and 80 ppm), including a deionized water control.
      Columns were repeatedly saturated with stormwater or deionized and then drained
      throughout 5 wk, with the last week of effluent analyzed for water chemistry. To
      examine bacterial communities, we extracted DNA from column bioretention media at
      time 0 and at week 5 and used molecular profiling techniques to examine bacterial
      community changes. We found that bacterial community taxa changed between time 0
      and week 5 and that there was significant separation between taxa among salt
      treatments. Bacteria evenness was significantly affected by stormwater treatment,
      but there were no differences in bacterial richness or diversity. Soil bacteria
      and salt treatments had a significant effect on the effluent concentration of NO,
      PO, Cu, Pb, and Zn based on ANOVA tests. The presence of bacteria reduced
      effluent NO and Zn concentrations by as much as 150 and 25%, respectively, while
      having a mixed effect on effluent PO concentrations. Our results demonstrate how
      stormwater can affect bacterial communities and how the presence of soil bacteria
      improves pollutant removal by green infrastructure.

PMID- 23128753
TI  - Assessment of existing roadside swales with engineered filter soil: I.
      Characterization and lifetime expectancy.
AB  - Roadside infiltration swales with well-defined soil mixtures (filter soil) for
      the enhancement of both infiltration and treatment of stormwater runoff from
      roads and parking areas have been common practice in Germany for approximately
      two decades. Although the systems have proven hydraulically effective, their
      treatment efficiency and thus lifetime expectancies are not sufficiently
      documented. The lack of documentation restricts the implementation of new such
      systems in Germany as well as other countries. This study provides an assessment
      of eight roadside infiltration swales with filter soil from different locations
      in Germany that have been operational for 6 to16 yr. The swales were assessed
      with respect to visual appearance, infiltration rate, soil pH, and soil texture,
      as well as soil concentration of organic matter, heavy metals (Cd, Cr, Cu, Pb,
      Zn), and phosphorus. Visually, the swales appeared highly variable with respect
      to soil color and textural layering as well as composition of plants and soil
      dwelling organisms. Three swales still comply with the German design criteria for
      infiltration rate (10 m/s), while the remaining swales have lower, yet
      acceptable, infiltration rates around 10 m/s. Six of the eight studied soils have
      heavy metal concentrations exceeding the limit value for unpolluted soil.
      Provided that the systems are able to continuously retain existing and incoming
      pollutants, our analysis indicates that the soils can remain operational for
      another 13 to 136 yr if the German limit values for unrestricted usage in open
      construction works are applied. However, no official guidelines exist for
      acceptable soil quality in existing infiltration facilities.

PMID- 23128754
TI  - Assessment of existing roadside swales with engineered filter soil: II. Treatment
      efficiency and in situ mobilization in soil columns.
AB  - Use of roadside infiltration systems using engineered filter soil for optimized
      treatment has been common practice in Germany for decades, but little
      documentation is available regarding their long-term treatment performance. Here
      we present the results of laboratory leaching experiments with intact soil
      columns (15 cm i.d., 25-30 cm length) collected from two German roadside
      infiltration swales constructed in 1997. The columns were irrigated with
      synthetic solutions of unpolluted or polluted (dissolved heavy metals and fine
      suspended solids) road runoff, as well as a soluble nonreactive tracer (bromide)
      and a dye (brilliant blue). The experiments were performed at two irrigation
      rates corresponding to catchment rainfall intensities of approximately 5.1 and 34
      mm/h. The bromide curves indicated that preferential flow was more pronounced at
      high irrigation rates, which was supported by the flow patterns revealed in the
      dye tracing experiment. Nonetheless, the soils seemed to be capable of retaining
      most of the dissolved heavy metals from the polluted road runoff at both low and
      high irrigation rates, except for Cr, which appears to pass through the soil as
      chromate. Fluorescent microspheres (diameter = 5 MUm) used as surrogates for fine
      suspended solids were efficiently retained by the soils (>99%). However, despite
      promising treatment abilities, internal mobilization of heavy metals and P from
      the soil was observed, resulting in potentially critical effluent concentrations
      of Cu, Zn, and Pb. This is mainly ascribed to high concentrations of in situ
      mobilized dissolved organic carbon (DOC). Suggestions are provided for possible
      improvements and further research to minimize DOC mobilization in engineered
      filter soils.

PMID- 23128755
TI  - Life cycle assessment of animal feeds prepared from liquid food residues: a case
      study of rice-washing water.
AB  - Life cycle assessment (LCA) was used to compare the greenhouse gas (GHG)
      emissions and energy consumption of three methods used to produce animal feed
      from concentrated rice-washing water (CRW) and disposing of the rice-washing
      water through wastewater treatment. Four scenarios were compared using LCA: (i)
      producing concentrated liquid feed by centrifugation (CC) of CRW with wastewater
      treatment and discharge of the supernatant, (ii) producing concentrated liquid
      feed by heating evaporation (HC) of CRW, (iii) producing dehydrated feed by
      dehydration (DH) of CRW, and (iv) wastewater treatment and discharge of
      nonconcentrated rice-washing water (WT). The functional unit (FU) was defined as
      1 metric ton of rice washed for cooking or processing. Our results suggested that
      the energy consumptions of CC, HC, DH, and WT were 108, 322, 739, and 242 MJ per
      FU, respectively, and the amounts of GHG emissions from CC, HC, DH, and WT were
      6.4, 15.8, 45.5, and 22.5 kg of CO equivalents per FU, respectively. When the
      produced feed prepared from CRW was assumed to be transported 200 km to farms, CC
      and HC still emitted smaller GHGs than the other scenarios, and CC consumed the
      smallest amount of energy among the scenarios. The present study indicates that
      liquid feed production from CRW by centrifugation has a remarkably reduced
      environmental impact compared with the wastewater treatment and discharge of rice
      washing water.

PMID- 23128756
TI  - Partial nitritation of swine wastewater in view of its coupling with the anammox
      process.
AB  - Partial nitritation (PN) of swine wastewater was investigated in a sequencing
      batch reactor (SBR) using a high-performance nitrifying sludge. Characteristics
      of the wastewater used were low content of biodegradable organic matter and a
      high alkalinity-to-ammonium ratio. The target oxidation of ammonium nitrogen (NH
      N) to nitrite nitrogen (NO-N) was 57% (1.32 g NO-N g NH-N), which corresponds
      with the reaction ratio of the anaerobic ammonium oxidation (anammox). This
      target was successfully achieved at 32 degrees C by controlling the inflow rate
      and the corresponding nitrogen loading rate (NLR). An average NLR of 1.47 g NH-N
      L d was applied to the partial nitritation sequencing batch reactor during a
      period of 70 d. The nitrite production rate obtained was 0.91 g NO-N L d. No
      nitrate was produced. The PN effluent contained 1.38 g NO-N g NH-N, which was
      within 5% of the target ratio. Under steady composition of the wastewater, the pH
      was shown to be a good indicator of the PN process performance. Furthermore, in a
      second sequencing batch reactor, the anaerobic ammonium oxidation process was
      effectively applied to the PN effluent, attaining a nitrogen conversion rate of
      0.36 g N L d (14.3 mg N g volatile suspended solids h).

PMID- 23128757
TI  - Nutrient leaching and soil retention in mined land reclaimed with stabilized
      manure.
AB  - Two environmental problems in Pennsylvania are degraded mined lands and excess
      manure nutrients from intensive animal production. Manure could be used in mine
      reclamation, but the large application rates required for sustained biomass
      production could result in significant nutrient discharge. An abandoned mine site
      in Schuylkill County, Pennsylvania, was used to test manure nutrient
      stabilization by composting and by mixing with primary paper mill sludge (PMS).
      Reclamation treatments were lime and fertilizer, composted poultry manure (78 and
      156 Mg ha), and poultry manure (50 Mg ha) mixed with PMS (103 and 184 Mg ha) to
      achieve C-to-N ratios of 20 and 29. Leachates were collected with zero-tension
      lysimeters, and during 3 yr following amendment application, <1% of added N
      leached from the compost treatments. The manure+PMS C:N 29 treatment leached more
      N than any other treatment (393 kg N ha during 3 yr, 12.4 times more N than
      compost treatments), mostly as pulses of NO in the first two fall seasons
      following reclamation. The manure+PMS C:N 20 treatment leached 107 kg N ha during
      3 yr. Three years after amendment application, most of the N and P added with the
      manure-based amendments was retained in the mine soil even though net
      immobilization of N by PMS appeared to be limited to 3 mo following application.
      Composting or mixing PMS with manure to achieve a C-to-N ratio of 20 can
      effectively minimize N leaching, retain added N in mine soil, and provide greater
      improvement in soil quality than lime and fertilizer amendment.

PMID- 23128758
TI  - Land application of manure and Class B biosolids: an occupational and public
      quantitative microbial risk assessment.
AB  - Land application is a practical use of municipal Class B biosolids and manure
      that also promotes soil fertility and productivity. To date, no study exists
      comparing biosolids to manure microbial risks. This study used quantitative
      microbial risk assessment to estimate pathogen risks from occupational and public
      exposures during scenarios involving fomite, soil, crop, and aerosol exposures.
      Greatest one-time risks were from direct consumption of contaminated soil or
      exposure to fomites, with one-time risks greater than 10. Recent contamination
      and high exposures doses increased most risks.  and enteric viruses provided the
      greatest single risks for most scenarios, particularly in the short term. All
      pathogen risks were decreased with time, 1 d to14 mo between land application and
      exposure; decreases in risk were typically over six orders of magnitude beyond 30
      d. Nearly all risks were reduced to below 10 when using a 4-mo harvest delay for
      crop consumption. Occupational, more direct risks were greater than indirect
      public risks, which often occur after time and dilution have reduced pathogen
      loads to tolerable levels. Comparison of risks by pathogen group confirmed
      greater bacterial risks from manure, whereas viral risks were exclusive to
      biosolids. A direct comparison of the two residual types showed that biosolids
      use had greater risk because of the high infectivity of viruses, whereas the
      presence of environmentally recalcitrant pathogens such as  and  maintained
      manure risk. Direct comparisons of shared pathogens resulted in greater manure
      risks. Overall, it appears that in the short term, risks were high for both types
      of residuals, but given treatment, attenuation, and dilution, risks can be
      reduced to near-insignificant levels. That being said, limited data sets, dose
      exposures, site-specific inactivation rates, pathogen spikes, environmental
      change, regrowth, and wildlife will increase risk and uncertainty and remain
      areas poorly understood.

PMID- 23128759
TI  - Denitrification and a nitrogen budget of created riparian wetlands.
AB  - Riparian wetland creation and restoration have been proposed to mediate nitrate
      nitrogen (NO-N) pollution from nonpoint agricultural runoff. Denitrification by
      anaerobic microbial communities in wetland soils is believed to be one of the
      main sinks for NO-N as it flows through wetlands. Denitrification rates were
      quantified using an in situ acetylene inhibition technique at 12 locations in
      three wetland/riverine sites at the Olentangy River Wetland Research Park,
      Columbus, Ohio for 1 yr. Sites included two created flow-through experimental
      wetlands and one bottomland forest/river-edge site. Points were spatially
      distributed at inflows, center, and outflows of the two wetlands to include
      permanently flooded open water, intermittently flooded transitions, and upland.
      Annual denitrification rates (median [mean]) were significantly higher ( < 0.001)
      in permanently flooded zones of the wetlands (266 [415] MUg NO-N m h) than in
      shallower transition zones (58 [37.5] MUg NO-N m h). Median wetland transition
      zone denitrification rates did not differ significantly ( >= 0.05) from riverside
      or upland sites. Denitrification rates peaked in spring; for the months of April
      through June, median denitrification rates ranged from 240 to 1010 MUg NO-N m h
      in the permanently flooded zones. A N mass balance analysis showed that surface
      water flux of N was reduced by 57% as water flowed through the wetland, but only
      about 3.5% of the N inflow was permanently removed through denitrification. Most
      N was probably lost through groundwater seepage. Comparison with denitrification
      rates measured previously in these wetlands suggests that these rates have
      remained steady over the past 4 to 5 yr.

PMID- 23128760
TI  - Soil nitrogen dynamics in a river floodplain mosaic.
AB  - In their natural state, river floodplains are heterogeneous and dynamic
      ecosystems that may retain and remove large quantities of nitrogen from surface
      waters. We compared the soil nitrogen dynamics in different types of habitat
      patches in a restored and a channelized section of a Thur River floodplain
      (northeast Switzerland). Our objective was to relate the spatiotemporal
      variability of selected nitrogen pools (ammonium, nitrate, microbial nitrogen),
      nitrogen transformations (mineralization, nitrification, denitrification), and
      gaseous nitrogen emission (NO) to soil properties and hydrological processes. Our
      study showed that soil water content and carbon availability, which depend on
      sedimentation and inundation dynamics, were the key factors controlling nitrogen
      pools and processes. High nitrogen turnover rates were measured on gravel bars,
      characterized by both frequent inundation and high sediment deposition rates, as
      well as in low-lying alluvial forest patches with a fine-textured, nutrient-rich
      soil where anaerobic microsites probably facilitated coupled nitrification
      denitrification. In contrast, soils of the embankment in the channelized section
      had comparatively small inorganic nitrogen pools and low transformation rates,
      particularly those related to nitrate production. Environmental heterogeneity,
      characteristic of the restored section, favors nitrogen removal by creating sites
      of high sedimentation and denitrification. Of concern, however, are the locally
      high NO efflux and the possibility that nitrate could leach from nitrification
      hotspots.

PMID- 23128761
TI  - High pollutant removal efficacy of a large constructed wetland leads to receiving
      stream improvements.
AB  - Hewletts Creek, in Wilmington, North Carolina, drains a large suburban watershed
      and as such is affected by high fecal bacteria loads and periodic algal blooms
      from nutrient loading. During 2007, a 3.1-ha wetland was constructed to treat
      stormwater runoff from a 238-ha watershed within the Hewletts Creek drainage. A
      rain event sampling program was performed in 2009-2010 to evaluate the efficacy
      of the wetland in reducing pollutant loads from the stormwater runoff passing
      through the wetland. During the eight storms sampled, the wetland greatly
      moderated the hydrograph and retained and/or removed 50 to 75% of the inflowing
      stormwater volume. High removal rates of fecal coliform bacteria were achieved,
      with an average load reduction of 99% and overall concentration reduction of
      >90%. Particularly high (>90%) reductions of ammonium and orthophosphate loads
      also occurred, and lesser but still substantial reductions of total phosphorus
      (89%) and total suspended solids loads (88%) were achieved. Removal of nitrate
      was seasonally dependent, with lower removal occurring in cold weather and a high
      percentage (90%+) of nitrate load removal occurring in the growing season when
      water temperature exceeded 15 degrees C. Long-term before-and-after sampling in
      downstream Hewletts Creek proper showed that, after wetland construction,
      statistically significant average decreases of 43% for nitrate, 72% for ammonium,
      and 59% for fecal coliform bacteria were realized. Wetland features contributing
      to the high pollutant control efficacy included available space for a large
      wetland, construction of deep forebays, and a dense and diverse aquatic and
      shoreline plant assemblage.

PMID- 23128762
TI  - Brain reorganization following weight loss.
AB  - The long-term stability of bodyweight despite wide variation in energy intake and
      expenditure suggests that at usual weight energy intake and output are 'coupled'
      to maintain body energy stores. Our model for some of the molecular mechanics of
      this regulation of energy stores is based on the concept of a neurally encoded
      'threshold' for minimum body fat, below which compensatory physiology is invoked
      to restore body fat. The existence of such a centrally encoded threshold is
      supported by the similarities in response to maintenance of a reduced weight
      between lean and obese individuals, and the tendency for weight-reduced
      individuals to regain weight to levels of fat stores similar to those present
      prior to initial weight loss. Brain responses to food and the observed changes in
      energy expenditure that occur during maintenance of a reduced weight are largely
      reversed by the administration of the adipocyte-derived hormone, leptin. .

PMID- 23128763
TI  - Physical activity and weight loss.
AB  - Weight loss interventions involving diet and physical activity typically result
      in 8-10% weight loss within 6-12 months after initiating treatment. Physical
      activity is a key component of these interventions for a variety of reasons.
      Weight loss achieved with physical activity averages approximately 1-3 kg, and
      the effects of physical activity on weight loss appear to be additive to what is
      observed with dietary restriction alone. Moreover, physical activity is an
      important behavior for prevention of weight regain and maintenance of significant
      weight loss resulting from dietary restriction, and physical activity contributes
      to weight loss in patients who have undergone bariatric surgery. However, there
      is significant interindividual variability in the weight loss resulting from
      physical activity, with both biological and behavioral factors contributing to
      this variability. Thus, additional research is needed to understand the role of
      physical activity in energy balance and body weight regulation, along with an
      understanding of the optimal intervention strategies to promote physical activity
      participation in overweight and obese individuals.

PMID- 23128764
TI  - Dietary strategies for weight management.
AB  - In an 'obesogenic' environment, getting people to eat appropriate amounts is
      challenging. Several food-based strategies have the potential to promote satiety
      and moderate energy intake. Components of foods such as macronutrients and
      functional ingredients can affect satiety; however, for weight management a more
      comprehensive approach is needed that emphasizes behavioral strategies to improve
      the overall diet. Research shows that large portions of energy-dense foods
      facilitate overconsumption and that reductions in portion size and energy density
      are associated with reduced energy intake. While this suggests that people should
      eat smaller portions, recent data show that if people lower the energy density of
      their diet, they can continue to eat their usual amount of food while limiting
      calories. Furthermore, serving larger portions of low-energy-dense foods can be
      used strategically to encourage their consumption and reduce dietary energy
      density, and this has been shown to be associated with decreased energy intake
      while maintaining satiety. This new understanding of how portion size can be used
      positively to manage energy intake has the potential to help people achieve
      sustainable improvements in their energy intake and bodyweight. Science-based
      strategies that increase the availability of affordable nutrient-rich, lower
      energy-dense foods are urgently needed.

PMID- 23128765
TI  - Targeting adipose tissue inflammation to treat the underlying basis of the
      metabolic complications of obesity.
AB  - The prevalence of obesity has increased throughout the last three decades due to
      genetic, metabolic, behavioral, and environmental factors [1]. Obesity in turn
      increases risk for a number of metabolic diseases including type 2 diabetes,
      cardiovascular disease, fatty liver disease and some forms of cancer [1]. Despite
      the well-known link between obesity and increased morbidity, the mechanism of
      this remains elusive. Thus, the question 'why does increased body fat cause
      increased metabolic comorbidities' remains unanswered. By understanding the
      underlying basis of obesity-associated metabolic diseases, different therapies
      could be designed to target relevant pathways. Although we lack a full
      understanding of the underlying mechanisms that result in disease, several
      putative explanations exist for why fat affects metabolic health. One such theory
      is based on the anatomic location of fat deposition and ectopic fat accumulation
      [2]. Specifically, current literature suggests that visceral, liver and skeletal
      fat accumulation affects organ function and contributes to the development of
      insulin resistance, fatty liver, and the metabolic syndrome [3]. However, even in
      individuals matched for body fat and fat distribution, significant differences
      can exist in metabolic outcomes, and the phenomenon of metabolically healthy
      obese has been well described [4]. More recent data suggest the alternative
      hypothesis relating excess adipose tissue to disease risk based on the metabolic
      function and morphological properties of adipose tissue. In this scenario, excess
      adipose tissue is hypothesized to contribute to a state of chronic inflammation
      which promotes development of insulin resistance as well as other metabolic
      complications by stimulating nuclear factor-KB and Jun N-terminal kinase pathways
      in adipocytes and the liver [5]. In this paper, we will review the hypothesis
      linking excess adipose tissue to increased disease risk through adipose tissue
      inflammation.

PMID- 23128767
TI  - The gut microbiome and obesity.
AB  - The composition of the gut microbiome is hypothesized to be an environmental
      factor that contributes to obesity. Results of several human studies suggest that
      obesity is associated with differences in the gut microbiota composition, reduced
      bacterial diversity, and altered representation of bacterial metabolic pathways.
      The obese phenotype is associated with increased microbial fermentation and
      energy extraction from non-digestible food components; however, until recently it
      was not clear how relatively small increases in energy extraction could
      contribute to the large and rapid weight gain observed in the animal studies.
      Mechanisms by which the gut microbiome may influence metabolism and energy
      homeostasis include regulation of energy uptake from diet, interaction with
      signaling molecules involved in host metabolism, modification of gut
      permeability, release of gut hormones, and low-grade, chronic inflammation, the
      latter being a hallmark of obesity-related diseases.

PMID- 23128768
TI  - Starting early: obesity prevention during infancy.
AB  - Obesity prevalence among infants and young children has increased rapidly during
      the past 4 decades, a disturbing trend given early obesity's association with
      later life obesity and its comorbidities. Fortunately, infancy is a period of
      great behavioral and metabolic plasticity offering numerous targets for
      preventive interventions. Modifiable factors that may affect early rapid weight
      gain and obesity risk include infant sleep duration, feeding to soothe infant
      distress, and the introduction of solid foods and transitional feeding. We
      discuss evidence linking these factors to weight outcomes, as well as results
      from behavioral obesity interventions in infancy, from our laboratory and
      others'. For example, in a recent pilot intervention, we focused on helping new
      mothers address three areas of infant behavior hypothesized to affect weight gain
      and early obesity risk: infant sleeping, crying, and feeding. First-time mothers
      were randomly assigned to receive either a Soothe/Sleep intervention, an
      Introduction of Solids intervention, both interventions, or no interventions. The
      interventions were delivered via home visits and showed positive effects on
      infant behaviors and weight outcomes at 1 year. Based on evidence from such pilot
      interventions, we assess the plausibility of targeting behavioral factors in
      infancy and suggest next steps for early prevention research.

PMID- 23128769
TI  - The economics of food choice behavior: why poverty and obesity are linked.
AB  - Obesity in the United States does not affect all segments of the population
      equally. It is more prevalent in deprived neighborhoods and among groups with
      lower education and incomes. Inequitable access to healthy foods is one mechanism
      by which socioeconomic factors can influence food choice behaviors, overall diet
      quality, and bodyweight. Having a supermarket in the immediate neighborhood has
      been linked to better diets and to lower obesity rates. However, the
      affordability of healthy foods may have more of an impact on food patterns than
      does distance to the nearest store. Grains, added sugars, and added fats are
      inexpensive, good-tasting, and convenient. Their consumption has been linked to
      lower quality diets, lower diet costs, and lower socioeconomic status. By
      contrast, the recommended healthier diets not only cost more but were consumed by
      more affluent groups. New techniques of spatial analysis are a promising approach
      to mapping obesity rates and linking them with measures of socioeconomic status
      based on diverse social and economic aspects of the built environment. Low
      residential property values predicted bodyweights of women better than did either
      education or incomes. Shopping in low-cost supermarkets was another powerful
      predictor of bodyweight. Bodyweight gain may be best predicted not by any one
      nutrient, food or beverage but by low diet cost. Higher obesity rates in poor
      neighborhoods may be the toxic consequence of economic insecurity. Alleviating
      poverty may be the best, if not the only, way to stop the obesity epidemic.

PMID- 23128771
TI  - The importance of systems thinking to address obesity.
AB  - Obesity is clearly a complex problem for both the individual and for society.
      Complex or 'wicked' problems have common characteristics such as heterogeneity,
      nonlinearity, interdependence, and self-organization. As such they require
      solutions appropriate for complex problems, rather than a reductionist search for
      the causes. 'Systems thinking' provides new ways to consider how to collectively
      address complex societal problems like obesity, where biology interacts with
      social, cultural and built environmental factors in infinite permutations and
      combinations. The systems that give rise to the obesity epidemic function at
      multiple levels, and there are important interactions between these levels. At
      any given level, individual actors and organizations matter and system function
      is optimized when individual and organizational capacity to respond is well
      matched to the complexity of individual tasks. Providing system supports to help
      networks of individuals become 'communities of practice' and 'systems of
      influence' may also help to accelerate the pace of effective action against
      obesity. Research efforts need to move away from the relentless search for the
      specific isolated causes of obesity and focus on solutions that have been shown
      to work in addressing other 'wicked' problems.

PMID- 23128770
TI  - The importance of the food and physical activity environments.
AB  - There is increasing interest in identifying characteristics of neighborhood
      environments (physical, social, economical) that might favor unhealthy dietary
      and physical activity patterns leading to excess weight at population level.
      Measurement of characteristics of the physical environment in relation to food
      and physical activity has greatly improved in recent years. Methods based on
      assessment of perceptions by residents of their neighborhood or on objective
      assessment of the actual built environment (such as provided by Geographic
      Information Systems tools) would benefit to be combined. A number of recent
      systematic reviews have updated our knowledge on relationships of food and
      physical activity environments with relevant behaviors and obesity. Available
      evidence appears to show more consistent evidence of association between built
      environment characteristics related to physical activity ('walkability' indices,
      land use mix, variety of transports. . .) with physical activity behavior than
      with weight status. In contrast, built environment characteristics related to
      food habits (accessibility to different types of food outlets, availability of
      healthy foods. . .) would be more consistently associated with weight status than
      with eating behavior. The need for data from different countries and cultures is
      emphasized, as much as the importance of transdisciplinary research efforts for
      translation of these findings into our living environment.

PMID- 23128773
TI  - Concluding remarks.

PMID- 23128774
TI  - Obesity. (Preface).

PMID- 23128775
TI  - Patient perceptions of a personal health record: a test of the diffusion of
      innovation model.
AB  - BACKGROUND: Personal health records (PHRs) have emerged as an important tool with
      which patients can electronically communicate with their doctors and doctor's
      offices. However, there is a lack of theoretical and empirical research on how
      patients perceive the PHR and the differences in perceptions between users and
      non-users of the PHR. OBJECTIVE: To apply a theoretical model, the diffusion of
      innovation model, to the study of PHRs and conduct an exploratory empirical study
      on the applicability of the model to the study of perceptions of PHRs. A
      secondary objective was to assess whether perceptions of PHRs predict the
      perceived value of the PHR for communicating with the doctor's office. METHODS:
      We first developed a survey capturing perceptions of PHR use and other factors
      such as sociodemographic characteristics, access and use of technology, perceived
      innovativeness in the domain of information technology, and perceptions of
      privacy and security. We then conducted a cross-sectional survey (N = 1500).
      Patients were grouped into five groups of 300: PHR users (innovators, other
      users, and laggards), rejecters, and non-adopters. We applied univariate
      statistical analysis (Pearson chi-square and one-way ANOVA) to assess differences
      among groups and used multivariate statistical techniques (factor analysis and
      multiple regression analysis) to assess the presence of factors identified by the
      diffusion of innovation model and the predictors of our dependent variable (value
      of PHR for communicating with the doctor's office). RESULTS: Of the 1500 surveys,
      760 surveys were returned for an overall response rate of 51%. Computer use among
      non-adopters (75%) was lower than that among PHR users (99%) and rejecters (92%)
      (P < .001). Non-adopters also reported a lower score on personal innovativeness
      in information technology (mean = 2.8) compared to 3.6 and 3.1, respectively, for
      users and rejecters (P < .001). Four factors identified by the diffusion of
      innovation model emerged in the factor analysis: ease of use, relative advantage,
      observability, and trialability. PHR users perceived greater ease of use and
      relative advantage of the PHR than rejecters and non-adopters (P < .001).
      Multiple regression analysis showed the following factors as significant positive
      predictors of the value of PHR for communicating with the doctor's office:
      relative advantage, ease of use, trialability, perceptions of privacy and
      security, age, and computer use. CONCLUSION: Our study found that the diffusion
      of innovation model fits the study of perceptions of the PHR and provides a
      suitable theoretical and empirical framework to identify the factors that
      distinguish PHR users from non-users. The ease of use and relative advantage
      offered by the PHR emerged as the most important domains among perceptions of PHR
      use and in predicting the value of the PHR. Efforts to improve uptake and use of
      PHRs should focus on strategies that enhance the ease of use of PHRs and that
      highlight the relative advantages of PHRs.

PMID- 23128776
TI  - Radiation-induced eye lens changes and risk for cataract in interventional
      cardiology.
AB  - BACKGROUND: Recent studies have reported a significant increase in eye lens
      opacities among staff in the cardiac catheterization laboratory but indicated
      further studies are needed to confirm the findings. OBJECTIVE: To evaluate the
      prevalence of opacities in eyes of cardiologists, radiographers and nurses
      working in interventional cardiology. METHODS: The eyes of 52 staff in
      interventional cardiology facilities and 34 age- and sex-matched unexposed
      controls were screened in a cardiology conference held in Kuala Lumpur by dilated
      slit-lamp examination, and posterior lens changes were graded. Individual
      cumulative lens X-ray exposures were calculated from responses to a questionnaire
      in terms of workload and working practice. RESULTS: The prevalence of posterior
      lens opacities among interventional cardiologists was 53%, while in nurses and
      radiographers it was 45%. Corresponding relative risks were 2.6 (95% CI: 1.2-5.4)
      and 2.2 (95% CI: 0.98-4.9), for interventional cardiologists and support staff,
      respectively. CONCLUSIONS: This study confirms a statistically significant
      increase in radiation-associated posterior lens changes in the eyes of
      interventional cardiology staff.

PMID- 23128778
TI  - Dysphagia characteristics in Zenker's diverticulum.
AB  - OBJECTIVES: To evaluate dysphagia characteristics in patients with Zenker's
      diverticulum (ZD). STUDY DESIGN: Case series with chart review. SETTING:
      Outpatient tertiary care dysphagia clinic. SUBJECTS AND METHODS: All ZD cases
      surgically treated over a 6-year period were identified and reviewed for
      dysphagia history and dysphagia characteristics on initial presentation using
      fiber-optic endoscopic evaluation of swallowing (FEES). Dysphagia symptoms and
      swallowing abnormalities were compared across groups based on diverticulum size
      (small <1 cm, medium 1-3 cm, and large >3 cm). RESULTS: Forty-six patients
      underwent a total of 52 procedures during the study period. ZD size was available
      in 49 cases (6 small, 26 medium, 17 large). Regurgitation symptoms were less
      frequent in patients with small (17%) compared with medium (68%) or large
      diverticula (76%; P = .03). Postswallow hypopharyngeal reflux (PSHR) was less
      frequent in patients with small (17%) compared with medium (91%) and large
      diverticula (87%; P < .01). PSHR was present on all FEES available for patients
      who presented with a recurrent or residual ZD (n = 7). In all cases, PSHR
      resolved after successful treatment of ZD. Pharyngeal residue indicating possible
      weakness was present in 24% of all patients at initial presentation. CONCLUSIONS:
      Preoperative assessment of dysphagia characteristics in ZD patients reveals that
      PSHR is predictive of a ZD larger than 1 cm and may be useful in surgical
      planning. PSHR is also helpful in identifying patients with recurrent or residual
      symptomatic ZD following surgical treatment. Pharyngeal weakness is present in a
      subset of ZD patients.

PMID- 23128779
TI  - The effect of vacuum freeze-drying and radiation on allogeneic aorta grafts.
AB  - Vacuum freeze-dried aorta is a satisfactory material for blood vessel grafting.
      Previous studies have focused on immunity, however, vacuum freeze-drying is a
      complicated process of heat and mass transfer, and adopting a programmed cooling
      process may more completely preserve the mechanical properties of the blood
      vessels. Irradiation, as a method of removing pathogens, lowers the antigenic
      activity of the blood vessels. In our study, vacuum freeze-drying combined with
      radiation was used as a treatment for porcine aorta prior to grafting, aimed at
      deactivating endogenous retrovirus, shielding masses of endothelial cells and
      lowering the immunogenicity of the blood vessels. As for the mechanical
      properties, compared with normal aorta, the maximum axial tensile stress (ATS)
      decreased by 20%, the maximum circumferential tensile stress (CTS) increased by
      30% and the maximum puncture stress (PT) decreased by 20%. Our results revealed
      that 2 months after of grafting, the host cells had migrated into the graft
      tissue and propagated to initiate endothelialization, the inflammatory reaction
      was abated and the PT had returned to normal levels. 

PMID- 23128781
TI  - Synthesis of ultrafine layered double hydroxide (LDHs) nanoplates using a
      continuous-flow hydrothermal reactor.
AB  - We report a novel continuous-flow hydrothermal method for the synthesis of
      layered double hydroxide (LDH) nanoplates. The precursor solutions may be fed to
      the reactor so that the production of LDHs occurs in a continuous mode. By
      control of the synthesis temperature, pressure and contact time, the synthesis of
      LDH nanoplates can be tuned with constant and consistent product quality. This
      very general and simple approach shows high potential for commercial scale-up.

PMID- 23128780
TI  - Skeletal muscle pericyte subtypes differ in their differentiation potential.
AB  - Neural progenitor cells have been proposed as a therapy for central nervous
      system disorders, including neurodegenerative diseases and trauma injuries,
      however their accessibility is a major limitation. We recently isolated Tuj1+
      cells from skeletal muscle culture of Nestin-GFP transgenic mice however whether
      they form functional neurons in the brain is not yet known. Additionally, their
      isolation from nontransgenic species and identification of their ancestors is
      unknown. This gap of knowledge precludes us from studying their role as a
      valuable alternative to neural progenitors. Here, we identified two pericyte
      subtypes, type-1 and type-2, using a double transgenic Nestin-GFP/NG2-DsRed mouse
      and demonstrated that Nestin-GFP+/Tuj1+ cells derive from type-2 Nestin-GFP+/NG2
      DsRed+/CD146+ pericytes located in the skeletal muscle interstitium. These cells
      are bipotential as they generate either Tuj1+ cells when cultured with muscle
      cells or become "classical" alpha-SMA+pericytes when cultured alone. In contrast,
      type-1 Nestin-GFP-/NG2-DsRed+/CD146+ pericytes generate alpha-SMA+pericytes but
      not Tuj1+ cells. Interestingly, type-2 pericyte derived Tuj1+ cells retain some
      pericytic markers (CD146+/PDGFRbeta+/NG2+). Given the potential application of
      Nestin-GFP+/NG2-DsRed+/Tuj1+ cells for cell therapy, we found a surface marker,
      the nerve growth factor receptor, which is expressed exclusively in these cells
      and can be used to identify and isolate them from mixed cell populations in
      nontransgenic species for clinical purposes.

PMID- 23128782
TI  - The mediating effect of parents' educational status on the association between
      adherence to the Mediterranean diet and childhood obesity: the PANACEA study.
AB  - OBJECTIVES: To investigate the potential mediating effect of parental education
      on the association between adherence to the Mediterranean diet and obesity, in 10
      12 years old children. METHODS: A cross-sectional survey was performed among
      1,125 (529 male) children in Greece. Children and their parents completed
      standardized questionnaires, which evaluated parents' educational level and
      dietary habits. Body mass index was calculated and children were classified as
      normal, overweight or obese (IOTF classification). Adherence to the Mediterranean
      diet was assessed using the KIDMED score. RESULTS: 27.7% of the children were
      overweight and 6.3% were obese; 12.3% of children reported high adherence to the
      Mediterranean diet. Multi-adjusted analysis, stratified by parental education,
      revealed that adherence to the Mediterranean diet was inversely associated with
      children's obesity status only in families in which at least one parent was of
      higher educational level (stratum-specific adjusted odds ratio: 0.41; 95% CI 0.17
      0.98), but not those in which both parents were of low educational level.
      CONCLUSIONS: Parental education status seems to play a mediating role in the
      beneficial effect of Mediterranean diet on children's obesity status.

PMID- 23128783
TI  - Investigation of threshold voltage instability induced by gate bias stress in ZnO
      nanowire field effect transistors.
AB  - We investigated the threshold voltage instability induced by gate bias (V(G))
      stress in ZnO nanowire (NW) field effect transistors (FETs). By increasing the
      V(G) sweep ranges and repeatedly measuring the electrical characteristics of the
      ZnO NW FETs, the V(G) stress was produced in the dielectric layer underneath the
      ZnO NW. Consequently, the electrical conductance of the ZnO NW FETs decreased,
      and the threshold voltage shifted towards the positive V(G) direction. This
      threshold voltage instability induced by the V(G) stress is associated with the
      trapping of charges in the interface trap sites located in the ZnO NW-dielectric
      interface. Our study will be helpful for understanding the stability of ZnO NW
      FETs during repetitive operations.

PMID- 23128784
TI  - Smoking among hospitalized patients: another opportunity to improve patients'
      health.

PMID- 23128785
TI  - Sanofi-cell research outstanding paper award of 2011.

PMID- 23128787
TI  - [Prison nursing].

PMID- 23128786
TI  - Clinical and Radiological Features of Stroke Patients with Poor Outcomes Who Do
      Not Receive Intravenous Thrombolysis because of Mild Symptoms.
AB  - BACKGROUND AND AIMS: A substantial proportion of patients who did not receive
      intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA),
      solely because of mild symptoms, can show poor outcome. The aim of our study was
      to analyze clinical and radiological features of the patients. METHODS: We
      enrolled 72 patients between 2007 and 2009 who presented to our hospital within 3
      h after stroke onset and who did not receive rtPA therapy solely because of mild
      symptoms (NIHSS score of <= 4 at rtPA decision), and examined detailed
      characteristics of patients with poor outcomes. Poor outcome was defined as a
      modified Rankin Scale score of >= 2 at 3 months after the stroke. RESULTS: Eleven
      of 72 patients (15%) had poor outcomes. Major vessel occlusion was observed in 7
      of the 11 patients. Neurological deterioration after admission was main reason
      for poor outcome. Infarct expansion in 6 patients (2 large artery diseases and 4
      small vessel diseases) and distal embolism by clot migration in 3 patients led to
      neurological deterioration. CONCLUSIONS: Clinical and radiological features of
      mild stroke patients with poor outcomes, who did not receive rtPA therapy, were
      identified. In such patients, intravenous thrombolysis may be justified.

PMID- 23128788
TI  - [Progress of clinical parameters amongst prison inmates receiving antiretroviral
      treatment].
AB  - INTRODUCTION: Among HIV positive patients the CD4 lymphocyte count, especially
      the viral load, are the best predictors for progress to full blown AIDS or death.
      OBJECTIVE: To analyze the factors associated with progress of the CD4 lymphocyte
      count and viral load in prison inmates in antiretroviral treatment. METHODS: A
      fixed cohort study was conducted with HIV positive inmates receiving
      antiretroviral therapy in three Spanish prisons. Adherence to antiretroviral
      treatment was assessed with the SMAQ questionnaire. To analyze the progress of
      CD4 and viral load clinical parameters, two fixed effect multilevel linear
      regression models were utilised. RESULTS: 10% of the sample were women, 42%
      referred for anxiety or symptoms of depression in the final week, and 46.6%
      reported having social support inside the prison. CD4 and viral load clinical
      parameter means were 2.48 and 2.89 respectively, and 38.6% had an undetectable
      viral load. A negative correlation between viral load and CD4 lymphocyte count
      (p<0.001) was found. Those inmates who did not present psychological morbidity
      showed a significant reduction in plasma viral load (p=0.017). CONCLUSIONS: The
      results of this study show the relevance of psychosocial factors in the immune
      system.

PMID- 23128789
TI  - [Comparisons between clinical practice consultation in a prison and in community
      health centres: differences and repercussions].
AB  - OBJECTIVES: To describe and quantify clinical practice consultancy in a prison
      health care unit so as to evaluate likely differences from a community Health
      Care Centre. To identify possible training needs when transferring health care
      staff from one system to another in the light of probable integration of Prison
      Health Care into the Public Health System. METHODS: A transversal descriptive
      study was used for three Primary Health Care teams: an urban health centre with a
      high work load, a rural health centre with a low work load, and the health care
      unit of a provincial prison (not a mega-prison). Ransom sequential sampling was
      used to include all the medical activity generated in the consultancy. All
      activity programmed by the health professional and administrative consultancy was
      excluded, while efforts were made to locate troubled consultations. Comparisons
      were made by contrasting differences in proportions. RESULTS: The Prison Health
      Care Unit showed higher statistically significant clinical activity in mental
      health, drug abuse, HIV and HCV infection management and specific Primary Health
      Care problems (biopsychosocial integration is a therapeutic priority). In both
      community Health Centres there is more statistically significant activity in
      Internal Medicine and Geriatrics. In the prison environment there is
      significantly higher troubled consultation. CONCLUSIONS: In a future context of
      integration of prison health care services into the Public Health Service,
      training in mental health care (especially addictive disorders) and in HIV-HCV
      infection management may be necessary for community health centre professionals
      wishing to transfer to prison health care units. The prison health care
      professional who wants to work in a public health centre may need training in
      Internal Medicine (especially Geriatrics). The statistically significant results
      for health care in prison, Primary Health Care and troubled consultation suggest
      that the GP plays a more active role in prison than in the community health
      centre. This should also be borne in mind when the intended integration of Prison
      Health Care into the Public Health Service takes place.

PMID- 23128790
TI  - [Unexplained phsyical complaints amongst prison inmates: diagnois and treatment].
AB  - Daily physiological processes, excess physical fatigue, subclinical viral
      infections and certain environmental situations can all cause some kind of
      physical pain or malaise in 75% of adults in a typical week. When the individual
      refuses to accept medical opinion and attributes the pain to a physical illness
      and persistently seeks diagnosis and treatment, then there is a possibility of an
      unexplained somatic problem. Depression, anxiety or even a personality disorder
      may be causative factors. The lack of studies of this type of disorder in the
      prison environment makes it difficult to fully evaluate the importance of this
      phenomenon for primary health care consultation in prison, despite the fact that
      the number of presented unexplained somatic complaints may well be the same as in
      the community (around 15%). Management of this type of patient is always
      difficult, complex and emotionally demanding for the health care professional.

PMID- 23128791
TI  - [Hallazgo incomodo].

PMID- 23128792
TI  - TP53 gene deletion in esophageal cancer tissues of patients and its clinical
      significance.
AB  - The aim of this study was to examine TP53 gene deletion in esophageal cancer (EC)
      tissues obtained from patients and to evaluate its clinical significance. Forty
      surgical specimens from patients with esophageal squamous cell carcinoma were
      examined for TP53 gene deletion using the fluorescence in situ hybridization
      (FISH) technique. Thirty-two male and 8 female patients were enrolled, with an
      average age of 56 years. TP53 gene deletion was significantly higher in poorly
      differentiated EC cases compared to well-differentiated cases (P=0.028). The TP53
      gene deletion rate was also significantly higher in the group with lymph node
      metastasis compared to the group without lymph node metastasis (P=0.0313). The
      TP53 gene deletion rate was shown to be correlated with the level of
      differentiation and lymph node metastasis in EC; it may therefore be an important
      molecular marker for evaluating the condition of EC in patients. 

PMID- 23128793
TI  - Immunosuppression in HCV-positive liver-transplant recipients.
AB  - PURPOSE OF REVIEW: The purpose of this review is to evaluate the historical and
      recent literature as it pertains to current immunosuppression regimens in
      hepatitis C virus (HCV)-positive (+) liver-transplant recipients. RECENT
      FINDINGS: Recent findings suggest that there are unique differences between HCV
      transplant recipients and non-HCV transplant recipients, not only in the graft's
      inflammatory response, but also to the treatments used to prevent and combat
      rejection. SUMMARY: HCV (+) transplant recipients present unique challenges. Over
      the years, there has been progress but there is clearly no consensus regarding
      the optimal immunosuppressive medications or drug regimens; however, there
      continues to be advancements in the management of patients with HCV. Though
      current studies do not provide clear evidence as to optimal immunosuppression,
      they do identify questions ideally addressed by large, randomized controlled
      trials.

PMID- 23128794
TI  - Dominant expansion of a cryptic subclone with an abnormal karyotype in B
      lymphoblastoid cell lines during culture.
AB  - Although B lymphoblastoid cell lines (B-LCLs) are thought to maintain their
      original genomic structures during long-term culture, there has been considerable
      disagreement on the actual genomic stability of these cells. This study was
      initiated to determine whether B-LCLs develop cell populations with abnormal
      genomes during culture and to search for factors important to the maintenance of
      the original genome. We established continuous cultures of B-LCLs for more than 6
      months and analyzed the cells using array-based comparative genome hybridization
      (CGH) analysis, conventional karyotyping and analysis of V(D)J recombination in
      the immunoglobulin (Ig) gene. We found that one B-LCL acquired an extra
      chromosome 4 without any other genomic rearrangements at passage 16 of continuous
      culture. At the Ig light- and heavy-chain loci, analysis of the major cell
      population showed a difference between cultures at early and later passages.
      Another aneuploid line was detected among B-LCLs established elsewhere and
      deposited previously into the RIKEN Cell Bank. Our findings indicate that some of
      the genomic rearrangements in B-LCLs are not caused by gradual accumulation of
      mutations and rearrangements during the B-LCL establishment processes, but rather
      as a result of a change in the cell population from clones with a normal genome
      to clones with de novo rearrangements. It is therefore feasible to maintain B
      LCLs with a normal genomic structure by cell cloning or similar treatment.

PMID- 23128795
TI  - Oestrogen alpha-receptor variant and two-year memory decline in midlife
      Australian women.
AB  - OBJECTIVE: To prospectively examine the influence of the oestrogen-alpha receptor
      (ESR1)PvuII polymorphism on changes in memory performance over a 2-year period
      among 80 midlife postmenopausal Australian women. METHODS: Healthy women aged 56
      67 years were administered a battery of four memory (verbal and non-verbal) tasks
      at baseline and 2 years later. RESULTS: Carriers of the ESR1 p allele had
      significantly greater declines in logical memory compared to participants with
      the PP genotype, independent of demographic characteristics (e.g. age), chronic
      illness (e.g. hypertension), sleep aid usage, hormone levels, apolipoprotein E e4
      status and prospective changes in mood, smoking and alcohol consumption.
      CONCLUSION: These findings provide preliminary evidence for larger and longer
      prospective trials that will be able to determine if the p allele of the
      ESR1PvuII polymorphism is a potential biomarker of logical memory decline among
      aging women.

PMID- 23128796
TI  - Dissociating the cognitive effects of levodopa versus dopamine agonists in a
      neurocomputational model of learning in Parkinson's disease.
AB  - BACKGROUND/AIMS: Levodopa and dopamine agonists have different effects on the
      motor, cognitive, and psychiatric aspects of Parkinson's disease (PD). METHODS:
      Using a computational model of basal ganglia (BG) and prefrontal cortex (PFC)
      dopamine, we provide a theoretical synthesis of the dissociable effects of these
      dopaminergic medications on brain and cognition. Our model incorporates the
      findings that levodopa is converted by dopamine cells into dopamine, and thus
      activates prefrontal and striatal D(1) and D(2) dopamine receptors, whereas
      antiparkinsonian dopamine agonists directly stimulate D(2) receptors in the BG
      and PFC (although some have weak affinity to D(1) receptors). RESULTS: In
      agreement with prior neuropsychological studies, our model explains how levodopa
      enhances, but dopamine agonists impair or have no effect on, stimulus-response
      learning and working memory. CONCLUSION: Our model explains how levodopa and
      dopamine agonists have differential effects on motor and cognitive processes in
      PD.

PMID- 23128797
TI  - A proposed compromise for national medical malpractice reform.

PMID- 23128798
TI  - Primary care physician shortage, healthcare reform, and convenient care: 
      challenge meets opportunity?

PMID- 23128799
TI  - Commentary on "Primary care physician shortage, healthcare reform, and convenient
      care: challenge meets opportunity?".

PMID- 23128800
TI  - Patient protection and affordable care act and physician's assistants.

PMID- 23128801
TI  - Outcomes of primary percutaneous intervention of the unprotected left main
      coronary artery stenosis in myocardial infarction.
AB  - OBJECTIVE: The aim of our study was to examine the 30-day and 1-year survival
      rate for patients undergoing percutaneous coronary artery intervention (PCI) of
      unprotected left main (ULM) stenosis by the presence (acute myocardial infarction
      [AMI] group) or absence (non-AMI group) of AMI at the time of hospital admission.
      METHODS: We retrospectively reviewed 64 patients undergoing PCI of ULM stenosis
      at our regional heart institute between 2000 and 2008. Patients had no history of
      coronary artery bypass grafting. RESULTS: Thirty-six men and 28 women underwent
      PCI for ULM stenosis. Overall Kaplan-Meier survival at 30 days and 1 year was
      71.5% and 57.8%, respectively. Thirty-three patients (51.6%) presented with AMI.
      Those with AMI had lower survival at both 30 days (59.2 vs 83.9%; P = 0.04) and 1
      year (45.2 vs 70.2%; P = 0.04) compared with those without AMI. Compared with a
      lesion involving only the ostial/mid LM, diffuse disease (N = 11) was associated
      with an increased mortality at 1 year (hazard ratio 0.27; 95% confidence interval
      0.09-0.79). A stent size >3 mm was associated with lower mortality at 1 year
      (hazard ratio 0.42; 95% confidence interval 0.19-0.93). CONCLUSIONS: We found
      that AMI at presentation was significantly associated with higher mortality in
      patients undergoing ULM stenting. LM lesion location and stent size were both
      significantly associated with mortality. ULM stenting is an option in patients
      who are unable to undergo coronary artery bypass grafting, but patients should
      understand the overall high risk of mortality, particularly if they present with
      AMI.

PMID- 23128802
TI  - Repeat pregnancy prevention self-efficacy in adolescents:  associations with
      provider communication, provider type, and depression.
AB  - OBJECTIVES: Among adolescent mothers, pregnancy prevention self-efficacy
      developed during pregnancy may predict the use of contraception following
      delivery. Communication between patients and their primary care providers (PCPs)
      is important for adherence to physician recommendations and may be associated
      with pregnancy prevention self-efficacy. Depression, which is common among
      adolescent mothers, has been associated with poor self-efficacy. The associations
      among pregnancy prevention self-efficacy, provider communication, provider type
      (PCP vs others), and depression are unclear. The objectives of the study were to
      determine the association of positive provider communication with pregnancy
      prevention self-efficacy, whether provider type or depression is associated with
      positive provider communication, and whether the association between provider
      communication and pregnancy prevention self-efficacy varies by provider type and
      depression. METHODS: Cross-sectional study of 164 third trimester Baltimore
      adolescents measuring pregnancy prevention self-efficacy, perceptions of the
      quality of provider communication (Ambulatory Care Experiences Survey), provider
      type, and depressive symptoms. RESULTS: Of 164 pregnant teens, 79% reported
      pregnancy prevention self-efficacy, 72% had a specific PCP, and 17% scored
      positive for depression. Positive provider communication was associated with
      pregnancy prevention self-efficacy (odds ratio 1.25; P = 0.04). Adolescents with
      PCPs had significantly higher communication scores (beta 0.90; P = 0.001).
      Depressed adolescents had significantly lower communication scores (beta -0.74; P
      = 0.03). The association between positive provider communication and self
      efficacy was significant only for adolescents who reported having a PCP (P =
      0.04) and those who were not depressed (P = 0.05). CONCLUSIONS: Having a PCP and
      favorable perceptions of provider communication are important for pregnancy
      prevention self-efficacy among adolescents. Depression negatively affects
      perceptions of provider communication, which may limit self-efficacy.

PMID- 23128803
TI  - Commentary on "Repeat pregnancy prevention self-efficacy in adolescents:
      associations with provider communication, provider type, and depression".

PMID- 23128804
TI  - Elderly adults and skin disorders:  common problems for nondermatologists.
AB  - Diseases of elderly adults are becoming increasingly important as life expectancy
      gradually rises worldwide. To promote healthy aging, it is important to
      understand the skin changes associated with aging. This review focuses on the
      special considerations for some of the more common dermatological disorders in
      elderly adults and examines presentation, contributing factors, and association
      with systemic diseases.

PMID- 23128805
TI  - Alcohol withdrawal.
AB  - Alcohol withdrawal is a common clinical condition that has a variety of
      complications and morbidities. The manifestations can range from mild agitation
      to withdrawal seizures and delirium tremens. The treatments for alcohol
      withdrawal include benzodiazepines, anticonvulsants, beta-blockers and
      antihypertensives. Although benzodiazepines are presently a first-line therapy,
      there is controversy regarding the efficacies of these medications compared with
      others. Treatment protocols often involve one of two contrasting approaches:
      symptom-triggered versus fixed-schedule dosing of benzodiazepines. We describe
      these protocols in our review and examine the data supporting symptom-triggered
      dosing as the preferred method for most patients in withdrawal.The Clinical
      Institute Withdrawal Assessment for Alcohol scoring system for alcohol withdrawal
      streamlines care, optimizes patient management, and is the best scale available
      for withdrawal assessment. Quality improvement implications for inpatient
      management of alcohol withdrawal include increasing training for signs of
      withdrawal and symptom recognition, adding new hospital protocols to employee
      curricula, and ensuring manageable patient-to-physician and patient-to-nurse
      ratios.

PMID- 23128806
TI  - Proton pump inhibitors:  the good, the bad, and the unwanted.
AB  - Proton pump inhibitors (PPIs) are one of the most commonly prescribed classes of
      medications in the United States. By inhibiting gastric H/K adenosine
      triphosphatase via covalent binding to the cysteine residues of the proton pump,
      they provide the most potent acid suppression available. Long-term PPI use
      accounts for the majority of total PPI use. Absolute indications include peptic
      ulcer disease, chronic nonsteroidal anti-inflammatory drugs use, treatment of
      Helicobacter pylori, and erosive esophagitis. Although PPIs are generally
      considered safe, numerous adverse effects, particularly associated with long-term
      use have been reported. Many patients receiving chronic PPI therapy do not have
      clear indications for their use, prompting consideration for reduction or
      discontinuation of their use. This article reviews the indications for PPI use,
      the adverse effects/risks involved with their use, and conditions in which their
      use is controversial.

PMID- 23128807
TI  - Carisoprodol:  update on abuse potential and legal status.
AB  - Carisoprodol is a centrally acting skeletal muscle relaxant of which meprobamate,
      a controlled substance, is the primary active metabolite. The abuse of
      carisoprodol has increased dramatically in the last several years. A withdrawal
      syndrome occurs in some patients who abruptly cease carisoprodol intake. The
      symptoms of this syndrome are similar to those seen with meprobamate withdrawal,
      suggesting that they may result from withdrawal from meprobamate accumulated with
      intake of excessive carisoprodol; however, carisoprodol is capable of modulating
      GABAA function, which may contribute to its abuse potential.There has been
      considerable debate about whether carisoprodol should be considered a controlled
      substance. Carisoprodol was removed from the market in Norway on May 1, 2008, but
      may still be used by specially approved patients. Carisoprodol was classified as
      a controlled substance in several US states, and effective January 11, 2012,
      became a schedule IV controlled substance at the US federal level. This article
      updates the literature on abuse potential and examines recent developments
      regarding the legal status of carisoprodol.

PMID- 23128808
TI  - Fat and fertility:  facts, failures, and the future.

PMID- 23128810
TI  - Per3 VNTR polymorphism and chronic heart failure.
AB  - AIMS: The aim of this study was to investigate the relationship between gene
      Period3 (Per3) variable number tandem repeat (VNTR) polymorphism and chronic
      heart failure (CHF). METHODS: The study subjects (372 patients of Caucasian
      origin with CHF and 332 healthy controls) were genotyped for Per3 VNTR
      polymorphism using an allele-specific PCR. RESULTS: No significant differences in
      genotype or Per3 VNTR allele frequencies were found between CHF cases and
      controls (Pg=0.30, Pa=0.52). No significant differences were uncovered either
      between CHF cases according to etiology (DCMP vs. IHD; Pg=0.87, Pa=0.91). In the
      multivariate regression modeling, no predictive function of VNTR Per3
      polymorphism on ejection fraction or NYHA class, hyperlipidaemia or type II
      diabetes risk was found. CONCLUSION: Per3 VNTR polymorphism is not a major risk
      factor for chronic heart failure or a factor modulating the severity of the CHF
      in this population.

PMID- 23128811
TI  - Procedure for granulocyte collection performed at the Blood Centre of the Faculty
      Hospital Ostrava.
AB  - BACKGROUND: Granulocyte apheresis is a safe and effective method for granulocyte
      collection. We present a five year experience (2006-2010) of the Blood Center,
      Faculty Hospital Ostrava, Czech Republic. Donor granulocyte transfusion is one
      treatment option for haemato-oncology patients with severe neutropenia
      complicated by bacterial/fungal infections unresponsive to standard
      antibiotic/antifungal treatment. In this study, we describe the experiences of
      the Blood Centre at the Faculty Hospital in Ostrava of granulocyte apheresis.
      METHODS AND RESULTS: A total of 149 granulocyte units were collected for 33
      patients from the Department of Haemato-oncology, University Hospital Olomouc,
      over a 5-year period (2006-2010). Information on donor selection, laboratory
      screening, mobilization regimen and granulocyte yield was obtained and analyzed.
      All mandatory screening tests for infection markers, AB0 and Rh and abnormal
      erythrocyte antibodies were performed. The cytomegalovirus status of the donors
      was not investigated. Steroids were the only mobilization regimen used, and were
      generally well accepted. The mean granulocyte yield was 12.6*10(9)/per
      transfusion unit (range 5.4-30.3). All granulocyte concentrates were irradiated
      and transfused according to AB0 Rh compatibility within 24 h after collection.
      CONCLUSION: Based on our experience, granulocytapheresis is a safe and effective
      method for obtaining granulocytes but the yield can be significantly influenced
      by other variables. From the recipients' perspective, the use of donor
      granulocytes supports an effective therapeutic modality.

PMID- 23128812
TI  - In vitro antimicrobial activities of cinnamon bark oil, anethole, carvacrol,
      eugenol and guaiazulene against Mycoplasma hominis clinical isolates.
AB  - AIMS: The aim of this study was to evaluate the antimicrobial effects of five
      natural substances against 50 clinical isolates of Mycoplasma hominis. METHODS
      AND RESULTS: The in vitro activity of selected natural compounds, cinnamon bark
      oil, anethole, carvacrol, eugenol and guaiazulene, was investigated against 50 M.
      hominis isolates cultivated from cervical swabs by the broth dilution method. All
      showed valuable antimicrobial activity against the tested isolates. Oil from the
      bark of Cinnamomum zeylanicum (MBC90 = 500 ug/mL) however was found to be the
      most effective. Carvacrol (MBC90 = 600 ug/mL) and eugenol (MBC90 = 1000 ug/mL)
      also possessed strong antimycoplasmal activity. CONCLUSIONS: The results indicate
      that cinnamon bark oil, carvacrol and eugenol have strong antimycoplasmal
      activity and the potential for use as antimicrobial agents in the treatment of
      mycoplasmal infections.

PMID- 23128813
TI  - The effect of environmental pollutants and food processing on the development of
      antibiotic resistance.
AB  - AIM: The purpose of this study was to determine how various compounds known to be
      positive mutagens, contribute to the development of mutations leading to
      ciprofloxacin resistance in Salmonella enterica subsp. enterica serotype
      Typhimurium. The molecular mechanism of ciprofloxacin resistance in treated
      strains was investigated. METHODS: A modified version of the incorporation plate
      test was used for quantitative determination of ciprofloxacin resistant mutants
      and for assessment of the mutation frequency induced by the positive mutagens in
      different concentrations. An AS-PCR-RFLP for monitoring of gyrA mutations was
      applied. RESULTS: Mutation frequency, expressed as number of antibiotic resistant
      colonies per 10(8) viable cells, was much higher after exposure of bacterial
      cells to 3-(5-nitro-2-furyl) acrylic acid and 2-nitrofluorene. All isolated
      cultures retain decreased susceptibility to antibiotic after multiple passages in
      antibiotic-free medium. 2-nitrofluorene was the best inducer of mutations in gyrA
      and in regulation genes affecting suppression of synthesis of outer membrane
      porins. 3-(5-nitro-2-furyl) acrylic acid gives rise to overproduction of efflux
      pump. CONCLUSIONS: The data suggest that antibiotic resistance may not be only a
      consequence of misuse of antibiotics. A polluted environment as well as food
      processing could contribute to this unwanted process.

PMID- 23128814
TI  - Concentrations of MMP-9 and TIMP-1 in lip tissue and their impact on cleft lip
      surgery healing.
AB  - AIM: To compare aspects of wound healing after cleft lip surgery performed within
      one week of age and wound healing after surgery performed within 2 - 4 months of
      age, especially concentrations of matrix metalloproteinase-9 (MMP-9) and tissue
      inhibitor of metalloproteinases-1 (TIMP-1) in tissue removed during surgery.
      METHODS: 34 tissue samples (26 boys and 8 girls) were removed during surgery
      within one week of age (n=19) or within 2 - 4 months of age (n=15). Tissue
      samples were separated into epidermis, dermis and mucous membrane. Proteins were
      extracted in cacodylic buffer for 24 h at a temperature 2 - 8 oC. Total protein
      concentrations were examined using a modification of the Lowry method. Samples
      were examined using ELISA kit Amersham Biotrak Activity Assay (GE Healthcare UK)
      for detection of MMP-9 and TIMP-1 concentrations. RESULTS: MMP-9: early surgery -
      epidermis 2.168 +/- 3.303 MUg/g of protein (mean +/- SD), dermis 1.251 +/- 1.848
      ug/g, 2 - 4 months surgery - epidermis 0.347 +/- 0.212 MUg/g, dermis 0.555 +/-
      0.276 ug/g. TIMP-1: early surgery - epidermis 1.762 +/- 2.162 MUg/g, dermis 1.628
      +/- 0.822 ug/g, mucous membrane 2.066 +/- 1.717 ug/g, 2 - 4 months surgery -
      epidermis 1.881 +/- 2.810 MUg/g, dermis 3.117 +/- 1.540 ug/g, mucous membrane
      4.833 +/- 6.550 ug/g. CONCLUSIONS: There were no significant differences in
      concentrations of protein MMP-9 in epidermis and dermis and TIMP-1 in epidermis
      and mucous membrane according to time of surgery. Significantly decreased levels
      of TIMP-1 in dermis were found in samples obtained from early surgery compared to
      levels in samples obtained from 2 - 4 months surgery.

PMID- 23128815
TI  - Safety and efficacy of sonothrombolysis using bilateral TCD monitoring by
      diagnostic 2 MHz probes - a pilot study.
AB  - INTRODUCTION: Sonothrombolysis is a new treatment method for patients with acute
      ischemic stroke (IS). Various ultrasound frequencies and intensities are being
      tested these days. The aim of this pilot study was to assess the safety and
      efficacy of sonothrombolysis using 2 diagnostic probes and bilateral monitoring
      in patients with acute occlusion of the middle cerebral artery (MCA). PATIENTS
      AND METHODS: Twelve consecutive IS patients (7 males; age 47 - 78, average 64.1
      +/- 9.4 years) with acute MCA occlusion and contraindication of thrombolysis were
      included in the study. 60-min bilateral 2-MHz pulsed-wave Doppler monitoring of
      the area of occlusion was performed in all patients (Group 1). The control group
      consisted of 37 IS patients (20 males; age 32 - 78, average 62.2 +/- 12.1 years)
      treated with standard sonothrombolysis and selected from the Thrombotripsy Study
      database (Group 2). The differences in number of recanalized arteries after a 1 h
      treatment, independent patients (modified Rankin scale [mRS] value of 0 - 2)
      after 90 days and symptomatic intracerebral hemorrhages (SICH) were statistically
      evaluated. RESULTS: Complete recanalization was found in 4 (30.0%) Group 1 and in
      12 (32.4%) Group 2 patients. Seven (58.3%) Group 1 and 22 (59.5%) Group 2
      patients were independent after 90 days. SICH was found in none of Group 1
      patients and in 1 (2.7%) of the Group 2 patients (P>0.05 in all cases).
      CONCLUSION: In this pilot study, sonothrombolysis using 2 probes and bilateral
      monitoring is safe but not more effective than standard sonothrombolysis in acute
      IS patients with MCA occlusion.

PMID- 23128816
TI  - Correlation between BRCA1 expression and clinicopathological factors including
      brain metastases in patients with non-small-cell lung cancer.
AB  - BACKGROUND: Previously identified as a breast and ovarian cancer susceptibility
      gene, BRCA1 has gained major scientific interest as a potential prognostic and/or
      predictive marker for various tumors, including non-small-cell lung cancer
      (NSCLC), the leading cause of cancer related mortality worldwide. BRCA1 plays a
      central role in DNA damage response (DDR. It undergoes phosphorylation by various
      DDR kinases at different serine residues, of which ser1524 is known to be
      specifically phosphorylated by ATM in response to genotoxic stress. METHODS: We
      performed BRCA1 immunohistochemistry on several tissue microarrays (TMAs) of 113
      early (I, II stage) and advanced (III, IV stage) NSCLCs, using MS110 antibody
      against the BRCA1 N-terminal and S1524 antibody against the phosphorylated form
      of BRCA1 protein at ser1524 (Abcam). Patients with III and IV stage disease were
      treated by adjuvant cisplatin-based chemotherapy. Staining results were
      correlated with overall survival (OS), disease free survival (DFS) and with the
      occurrence of brain metastases. RESULTS: BRCA1 S1524 nuclear positivity was
      significantly correlated with longer OS and DFS in stage I and II patients
      (P<0.05), while OS and DFS were shorter in S1524 positive stage III and IV
      patients (P<0.05). No significant correlation was found with brain metastases.
      CONCLUSION: The results show that BRCA1 phosphorylaton, at least in ser1524,
      differentiates the fate of early and advanced NSCLC as well as response to
      chemotherapy, but the underlying mechanisms are not completely understood.
      Detection of phosphorylated forms of BRCA1 might serve as a useful prognostic and
      predictive marker for patients with NSCLC.

PMID- 23128817
TI  - Beta 2 adrenergic receptor polymorphisms, at codons 16 and 27, and bronchodilator
      responses in adult Venezuelan asthmatic patients.
AB  - BACKGROUND: One of the gene polymorphisms often studied in asthmatic patients is
      the beta2 adrenergic receptor (ADRbeta2). Even though in the Venezuelan Mestizo
      population there is a high incidence of asthma, there are no direct reports of
      ADRbeta2 gene polymorphism, and treatment response. The aim of this study was to
      assess, in this population, the gene frequency of ADRbeta2 polymorphisms at
      codons 16 Arg/Gly and 27 Gln/Glu, allergen sensitization, and its relationship to
      bronchodilator response. METHODS: Purified genomic DNA was obtained form 105
      Mestizo asthmatic and 100 Mestizo healthy individuals from Venezuela. The two
      polymorphisms were assessed by PCR-RFLP. Patient sensitization to aeroallergens
      and their response to bronchodilatation were correlated. RESULTS: Significant
      differences between patients and controls were recorded in: 1) the prevalence of
      Arg/Arg at codon 16 (28.6% in patients vs. 47% in controls, P<0.01), 2) the
      frequency of heterozygotes Arg/Gly (55% in patients vs. 35% in controls, P<0.01).
      Conversely, no differences in polymorphism frequencies were found at codon 27.
      The haplotypes Arg/Gly-Gln/Gln were more common in patients than controls (P
      <0.01), whereas the Arg/Arg-Gln/Glu combination prevailed in the control group
      (P<0.01). The Arg/Gly and Gln/Glu genotypes were associated with better responses
      after salbutamol. The asthmatic homozygotes Arg/Arg have higher sensitivity to
      aeroallergens. CONCLUSION: The difference in Arg/Arg frequency between groups
      suggests that this could be a protective genotype although the asthmatic group
      had a higher sensitivity to aeroallergens. The asthmatic heterozygotes had better
      bronchodilator responses than the homozygotes.

PMID- 23128818
TI  - Comparison of parturient - controlled remifentanil with epidural bupivacain and
      sufentanil for labour analgesia: randomised controlled trial.
AB  - INTRODUCTION: Epidural analgesia (EA) has significant contraindications including
      coagulation disorders and parturient refusal. One alternative is intravenous self
      administered analgesia using the ultra short-acting opioid remifentanil (rPCA).
      We compared the efficiency and safety of standard epidural analgesia with
      parturient-controlled intravenous analgesia using remifentanil as well as
      personal satisfaction. MATERIALS AND METHODS: We enrolled twelve ASA I classified
      women with singleton pregnancy who delivered vaginally in the period 3/2010
      5/2010 and who received rPCA (n=12) in standard analgesic protocol: 20 ug boluses
      using PCA pump with a lockout interval of 3 min. The control group consisted of
      12 pregnant women who received EA (n=12): 0.125% bupivacaine with sufentanil 0.5
      ug/mL in top-up boluses every hour until delivery. Data were acquired from
      standard Acute Pain Service (APS) form and patient medical records (demographic,
      labour course parameters), Visual Analogue Scale (VAS), Bromage Scale (BS) and
      adverse effects of analgesia. RESULTS: There were no demographic or labour course
      parameter differences between groups (P>0.05). The differences in VAS decrease
      (P=0.056) and parturient satisfaction (P=0.24) during the whole analgesia
      administration were statistically insignificant. The main limitation of the study
      was small sample and enrolment of healthy singleton pregnant women only.
      CONCLUSION: Remifentanil use in obstetric analgesia is a viable alternative to
      EA, especially in cases of EA contraindications and parturient disapproval.

PMID- 23128819
TI  - Occult tumour cells in peritoneal lavage are a negative prognostic factor in
      pancreatic cancer.
AB  - AIMS: The aim of this study was to test the hypothesis that occult tumour cells
      in peritoneal lavage are a negative prognostic factor in pancreatic
      adenocarcinoma. METHODS: Real-time RT-PCR analysis of CEA, EGFR and hTERT
      transcript levels was used to identify occult tumour cells in peritoneal lavage
      samples from 96 pancreatic cancer patients. RESULTS: We found significant
      association between CEA expression levels in peritoneal lavage and clinical
      stage. We also found that EGFR transcript levels were higher in peritoneal lavage
      samples from patients with high grade tumours than in samples from patients with
      low grade tumours. Detection of CEA and/or EGFR occult tumour cell markers in the
      peritoneal lavage was associated with significantly shorter overall survival and
      increased hazard ratio for disease recurrence. CONCLUSIONS: The results show that
      the presence of occult tumour cells in peritoneal lavage is a negative prognostic
      factor for survival in pancreatic cancer patients, and that detection of occult
      tumour cells using PCR-based methods can identify patients with advanced disease
      for whom radical surgery is likely to have little benefit.

PMID- 23128820
TI  - Arrhythmias and ECG changes in life threatening hyperkalemia in older patients
      treated by potassium sparing drugs.
AB  - BACKGROUND: Severe hyperkalemia is a life threatening condition that can cause
      fatal rhythm disturbance and terminal heart arrest. The most common cause of
      hyperkalemia in older patients is that of iatrogenic medication-related etiology
      due to associated polymorbidity, polypharmacy and reduced reserve metabolic
      capacity. The aim of this paper is to increase awareness in the clinicians of the
      risk of hyperkalemia in elderly patients treated by potassium sparing drugs.
      METHODS AND RESULTS: We present two case reports of hyperkalemia >= 9.0 mmol/L
      induced by potassium sparing medications with cardiac arrhythmias and severe ECG
      changes including atrial asystole, disturbance of intraventricular conduction and
      morphological changes such as tenting T waves and deformed wide QRS complexes.
      The most frequent causes of hyperkalemia in elderly patients are discussed and
      electrocardiogram changes and arrhythmias in hyperkalemia are analyzed, as well
      as their treatment and prevention. CONCLUSION: Potassium sparing drug therapy in
      older persons requires more frequent monitoring especially when drugs or their
      doses are changed, or during concomitant acute illness.

PMID- 23128821
TI  - Cytotoxic effects of Fisturalin-3 and 11-Deoxyfisturalin-3 on Jurkat and U937
      cell lines.
AB  - BACKGROUND: Fisturalines are bromotyrosine compounds isolated from marine
      sponges. Previous studies have shown antineoplasic, antiviral and antibacterial
      effects in Vitro; however, the possible effects of these compounds in hematologic
      malignancies have not been assessed. METHODS: In the present study, the
      antiproliferative and pro apoptotic effects of Fistularin-3 (F) and 11
      Deoxyfistularin-3 (DF) were assessed using the MTT method and annexin V/propidium
      iodide by flow cytometry using the cell lines: Jurkat E6.1 and U937. In addition,
      the cell cycle was assessed by flow cytometry. RESULTS: Inhibition of the
      proliferative response was concentration and time dependent. The IC50 of F was
      7.39 and 8.10 uM for Jurkat E6.1 and U937 respectively. At 24 and 48 h, in the
      U937 cell line, but not in the Jurkat cell line, both compounds induced up to 35%
      annexin V increase. Necrosis was not observed in any case. Compound F induced, in
      both cell lines, a decrease in the number of cells in the S phase and increase in
      the G0/G1 phase. In the Jurkat cell line only, there was an increase in the
      number of cells in the G2/M phase. Compound DF was not as effective as F.
      CONCLUSIONS: F is more active than DF in repressing the cell cycle and inducing
      apoptosis. Both compounds are potentially useful in the development of new drugs
      to treat hematologic malignancies.

PMID- 23128822
TI  - The effect of spironolactone in patients with resistant arterial hypertension in
      relation to baseline blood pressure and secondary causes of hypertension.
AB  - AIMS: There are currently limited data about whether the effect of spironolactone
      in patients with resistant arterial hypertension depends on baseline blood
      pressure and the presence of a secondary cause of hypertension. METHODS: Patients
      with office systolic blood pressure (BP) >140 mmHg or diastolic BP >90 mmHg,
      despite treatment with at least 3 antihypertensive drugs including a diuretic,
      were randomly assigned to receive spironolactone or a placebo for 8 weeks in a
      double-blind, placebo-controlled, multicentre trial (ASPIRANT). RESULTS: Analyses
      were done with 55 patients treated with spironolactone. The degree of BP
      reduction after 8 weeks of spironolactone treatment did not differ significantly
      between the three tertiles of baseline systolic BP and patients with and without
      a secondary cause of hypertension. The reduction of office systolic, office
      diastolic BP and office pulse pressure was significantly lower in the highest
      tertile with baseline diastolic BP > 97 mmHg. CONCLUSIONS: Spironolactone
      treatment is effective to a similar extent both in patients with and without a
      secondary cause of hypertension and regardless of the baseline value of systolic
      BP. Less effect of spironolactone was found in patients with the highest baseline
      diastolic BP.

PMID- 23128823
TI  - The variable clinical course of peripartum cardiomyopathy.
AB  - BACKGROUND: In Europe, peripartum cardiomyopathy (PPCM) is a rare disorder, often
      difficult to diagnose and it has a variable clinical course. The aim of this
      report was to describe and discuss the individual variability of this disorder
      and its management. PATIENTS AND METHODS: Three cases of PPCM manifesting as
      severe heart failure are compared. Common was the presence of myocardial
      inflammation detected by endomyocardial biopsy. Different were treatment methods
      and clinical course. Modern therapeutic concepts such as immunosuppressive
      therapy and bromocriptin administration are discussed, as well as non
      pharmacological approaches. CONCLUSION: In the differential diagnostics of
      dyspnea associated with pregnancy and childbirth, PPCM should be considered. The
      potentially severe course of the disease requires hospitalization with the
      possibility of comprehensive heart failure treatment, including non
      pharmacological approaches such as device therapy and heart transplantation.

PMID- 23128824
TI  - Combination of prednisolone and low dosed dexamethasone exhibits greater in vitro
      antileukemic activity than equiactive dose of prednisolone and overcomes
      prednisolone drug resistance in acute childhood lymphoblastic leukemia.
AB  - INTRODUCTION: Glucocorticoids, particularly prednisone/ prednisolone and
      dexamethasone, play a prominent role in the treatment of pediatric patients with
      acute lymphoblastic leukemia due to their ability to induce apoptosis in
      susceptible cells. Current therapeutic protocols use prednisone for both the
      prophase and the induction phase of the therapy because the greater antileukemic
      activity of dexamethasone is compromised by its high frequency of serious adverse
      reactions. AIM: To compare, for the first time, the in vitro antileukemic
      activity of prednisolone alone to that of a combination of prednisolone and
      dexamethasone using dexamethasone at a very low and presumably safe dosage (1/50
      w/w). METHODS: Lymphoblasts were isolated from bone marrow and/or blood samples
      from children with newly diagnosed acute lymphoblastic leukemia. The cytotoxic
      activity of prednisolone, dexamethasone and the prednisolone/dexamethasone
      combination against isolated leukemia cells was analyzed using the MTT
      cytotoxicity assay. RESULTS: We observed differences in the in vitro antileukemic
      activity of prednisolone and dexamethasone in 21% of the tested patients. 3% of
      the children were prednisolone sensitive but dexamethasone resistant, while 18%
      were prednisolone resistant and dexamethasone sensitive. 32% were sensitive to
      both glucocorticoids and 18% were resistant to both. Cells from patients with
      good in vivo responses to prednisone monotherapy were more responsive to
      prednisolone in vitro than were cells from patients with poor prednisone
      responses (P<0.07). Importantly, we demonstrated that the use of even a minimal
      dose (1/50 w/w) of dexamethasone with prednisolone dramatically increases the in
      vitro anti-leukemic activity of prednisolone (P<0.0006). CONCLUSION: The high
      inter-individual variability of acute lymphoblastic leukemia responses to
      glucocorticoids suggest that either patients should be selected for prednisone or
      dexamethasone treatment on the basis of predictive biomarkers or that prednisone
      should be used directly in combination with a very low and safe dose of
      dexamethasone to potentiate its antileukemic activity. The latter option is
      likely to be cheaper and more efficient, and therefore warrants further clinical
      investigation to assess its efficacy and safety in treating childhood acute
      lymphoblastic leukemia.

PMID- 23128825
TI  - Malignant melanoma in the Czech Republic: incidence and mortality according to
      sex, age and disease stage.
AB  - BACKGROUND: The Czech Republic has reported one of the highest incidence rates of
      cutaneous melanoma (CM) in Europe and the rate continues to rise. Our study
      undertook a detailed investigation of the incidence and mortality of melanoma
      relative to sex, age and disease stage. The main goals were to elucidate the
      causes of the rising trends and explain the differences in development relative
      to sex, age and disease stage. METHODS AND RESULTS: The estimated annual
      percentage change (EAPC) using the Joinpoint Regression Model was calculated
      separately for men and women for all age categories and for all T stages of TNM
      classification. The EAPC for women was slightly higher than for men. This was
      only found in melanomas thinner than 1 mm (T1). For all other stages (T2, T3 and
      T4) the situation was worse in men. A higher incidence rate of CM and the higher
      value of EAPC were found for women in younger age categories (up to 49 years). In
      the next age category, from 50 to 59 years, the incidence of CM was comparable in
      both sexes as well as the EAPC. In the older age categories, i.e. 60 years and
      older, a significant increase was found predominantly in men. The mortality rates
      were only comparable between men and women in the 20 to 29 year age group. In all
      other categories there was a higher mortality for men. CONCLUSIONS: The number of
      melanoma cases in the Czech Republic is increasing faster than any other cancer.
      Despite improved survival rates, the death rate from CM continues to climb as a
      result of exponential increases in incidence. Thus primary and secondary
      prevention campaigns are essential for future reductions in CM incidence and
      mortality in the Czech Republic.

PMID- 23128826
TI  - Laparoscopic abdominoperineal resection with intraoperative radiotherapy for
      locally advanced low rectal cancer.
AB  - AIMS: Intraoperative radiotherapy (IORT) for locally advanced rectal cancer as an
      integral part of multimodal treatment, may lead to reduced local recurrence but
      it is not routinely used. The aim of this paper is to describe our experience
      with IORT in the treatment of patients with locally advanced adenocarcinoma of
      the lower third of the rectum. MATERIAL AND METHODS: Laparoscopic
      abdominoperineal amputation of the rectum with intraoperative radiotherapy was
      performed on 17 patients, 13 men and 4 women, median age 64 years (49-75 years)
      between 2010-2011. All patients underwent complete therapy according to the
      treatment protocol. RESULTS: In one patient, the laparoscopic procedure had to be
      converted to an open resection. The duration of the surgical procedure with IORT
      was 185 to 345 min (median 285 min). In 14 cases, the intraoperative dose was 10
      Gy and in two patients a dose of 12 Gy was used. There were no severe
      intraoperative complications. Blood loss ranged from 30 to 500 mL (median 100
      mL). There were postoperative complications in 4 patients (23.5%); 2 necessitated
      surgical reintervention (11.8%). The duration of postoperative hospitalization
      was 6 to 35 days (median 7 days). In the follow-up of 2 to 16 months (median 12
      months), no local recurrence or disease generalization have been found to date.
      CONCLUSIONS: The results show the technical feasibility of laparoscopically
      assisted abdominoperineal amputation of the rectum in combination with IORT in
      the treatment of locally advanced rectal carcinoma with an acceptable risk of
      postperative complications.

PMID- 23128827
TI  - Unusual recurrent rectal carcinoma: a cancer field theory viewpoint.
AB  - AIM: The rate of rectal cancer locoregional recurrence following radical surgery
      varies from 4% to 33%. Though the causes are unclear, likely factors include
      microscopic tumor residues in the lymphatics, positive resection margins and
      exfoliation of tumor cells and their subsequent intraluminar spread during
      operation. Other significant factors include type and technique of surgical
      procedure. Recently, it has been demonstrated that local recurrence may also be
      associated with the biological behaviour of the tumor and/or with the composition
      of the cellular microenvironment which creates optimal conditions for the growth
      and spread of tumor cells. CASE REPORT: The presented case here is interesting
      because the tumour recurred early following a curative surgical procedure with
      negative resection margins, without positive lymph nodes, without infiltration of
      the pelvic wall and without distant metastases. CONCLUSION: In patients with a
      determined risk of genetically altered tumor field encompassing epithelial or
      stromal changes, a different treatment strategy, including gene therapy, anti
      inflammatory or anti-angiogenic therapy should be chosen to minimize increased
      tumor risk.

PMID- 23128829
TI  - Induction of nuclear anomalies in exfoliated buccal cells of coca chewers:
      results of a field study.
AB  - The leaves of coca (Erythroxylum coca var. coca), a South American shrub which
      contains cocaine, other alkaloids and phenolics are widely used by indigenous
      populations of the Andes. It is currently not known if coca consumption causes
      genotoxic effects in humans. This information is important to predict potential
      long-term toxic effects such as cancer induction. Therefore, the buccal cytome
      assay was used to analyze oral cells from 45 uni- and bilateral chewers and 23
      controls living in the Altiplano of the Peruvian Andes. In total, 123,471 cells
      were evaluated from chewers and 57,916 from controls. Information concerning the
      consumption levels and habits and also use of lime were collected with
      questionnaires. Chewing of the leaves did not induce nuclear anomalies reflecting
      genetic damage such as micronuclei (MNi) and nuclear buds; in the highest
      exposure group (but not in the overall group) even a significant decrease in the
      frequencies of cells with MNi (by 64 %) was observed. However, we found
      significantly elevated levels of other nuclear anomalies (karyorrhexis and
      karyolysis) which reflect cytotoxic effects in the coca users. The frequencies of
      these anomalies increased with the daily consumption and when lime was used to
      improve the release of the alkaloids. In contrast to other chewing habits (betel,
      tobacco and khat), consumption of coca leaves does not induce genetic instability
      in cells from the oral cavity and our findings indicate that no adverse health
      effects take place in chewers which are associated with DNA damage. However, the
      significant increase in certain anomalies shows that acute toxic effects are
      caused by coca consumption.

PMID- 23128830
TI  - Buckyballs (fullerenes): free radical sponges or inflammatory agents?

PMID- 23128831
TI  - Rescue valve-in-valve implantations in second generation transapical
      transcatheter aortic valve prostheses.

PMID- 23128832
TI  - Sorafenib is effective in the treatment of pulmonary veno-occlusive disease.
AB  - The present study is the first report of the effectiveness of sorafenib in the
      treatment of pulmonary veno-occlusive disease (PVOD). A 66-year-old woman with
      PVOD was started on sorafenib. After 3 months of treatment with a maximum dosage
      of 400 mg/day sorafenib, there was an improvement in the patient's New York Heart
      Association (NYHA) functional class from IV to III. However, because of severe
      painful eruptions as a side effect of sorafenib, the patient stopped sorafenib
      and was started on imatinib instead. This treatment resulted in a worsening of
      the patient's NYHA class from III to IV, so sorafenib was restarted at a reduced
      dosage of 300 mg/day. The resumption of sorafenib was associated with clinical
      improvement, specifically NYHA class from IV to II and hemodynamic amelioration,
      and tolerable eruptions. In conclusion, sorafenib may be a potential therapeutic
      strategy for the treatment of PVOD.

PMID- 23128833
TI  - Cobalt phosphite microarchitectures assembled by ultralong nanoribbons and their
      application as effective electrochemical capacitor electrode materials.
AB  - Cobalt phosphite (Co(11)(HPO(3))(8)(OH)(6)) microarchitectures assembled by
      ultralong nanoribbons are successfully synthesized by a mild hydrothermal
      condition without any additives. The uniform ultralong nanoribbon has a width of
      100 nm and length of 20-30 MUm. More importantly, Co(11)(HPO(3))(8)(OH)(6)
      microarchitectures are also successfully applied as an electrochemical
      supercapacitor with a good specific capacitance (312 F g(-1) at 1.25 A g(-1)),
      good rate capability and excellent cycling property (maintaining about 89.4% at
      1.25 A g(-1) after 3000 cycles).

PMID- 23128834
TI  - Attenuation of brain edema and spatial learning deficits by the inhibition of
      NADPH oxidase activity using apocynin following diffuse traumatic brain injury in
      rats.
AB  - Diffuse brain injury (DBI) is a leading cause of mortality and disability among
      young individuals and adults worldwide. In specific cases, DBI is associated with
      permanent spatial learning dysfunction and motor deficits due to primary and
      secondary brain damage. Nicotinamide adenine dinucleotide phosphate (NADPH)
      oxidase (NOX) is a major complex that produces reactive oxygen species (ROS)
      during the ischemic period. The complex aggravates brain damage and cell death
      following ischemia/reperfusion injury; however, its role in DBI remains unclear.
      The present study aimed to investigate the hypothesis that levels of NOX2 (a
      catalytic subunit of NOX) protein expression and the activation of NOX are
      enhanced following DBI induction in rats and are involved in aggravating
      secondary brain damage. A rat model of DBI was created using a modified weight
      drop device. Our results demonstrated that NOX2 protein expression and NOX
      activity were enhanced in the CA1 subfield of the hippocampus at 48 and 72 h
      following DBI induction. Treatment with apocynin (50 mg/kg body weight), a
      specific inhibitor of NOX, injected intraperitoneally 30 min prior to DBI
      significantly attenuated NOX2 protein expression and NOX activation. Moreover,
      treatment with apocynin reduced brain edema and improved spatial learning
      function assessed using the Morris water maze. These results reveal that
      treatment with apocynin may provide a new neuroprotective therapeutic strategy
      against DBI by diminishing the upregulation of NOX2 protein and NOX activity. 

PMID- 23128835
TI  - Enoxaparin outcomes in patients with moderate renal impairment.
AB  - BACKGROUND: Enoxaparin sodium has predictable pharmacokinetics that allow for
      simplified dosing without laboratory monitoring. Reliance on renal function for
      excretion may lead to accumulation of enoxaparin in patients with moderate renal
      impairment. However, there is no dose adjustment recommended for these patients.
      We conducted a review to compare bleeding events in patients with moderate renal
      impairment compared with those with normal renal function. METHODS: Patients
      received enoxaparin sodium, 1 mg/kg, every 12 hours or 1.5 mg/kg once daily
      between June 1 and November 30, 2009. Moderate renal impairment was defined as
      creatinine clearance (CrCl) of 30 to 50 mL/min. Normal renal function was defined
      as CrCl greater than 80 mL/min. The primary outcome was major bleeding, defined
      as any bleeding resulting in death, hospital admission, lengthened hospital stay,
      or an emergency department visit. The secondary outcome was thromboembolism.
      RESULTS: A total of 164 patients met the inclusion criteria: 105 with normal
      renal function and 59 with moderate renal impairment. The primary outcome
      occurred in 6 of 105 patients (5.7%) with normal renal function vs 13 of 59
      patients (22.0%) with moderate renal impairment, representing an unadjusted odds
      ratio of 4.7 (95% CI, 1.7-13.0; P = .002). The odds ratio using multivariable
      logistic regression adjusting for differences in risk was 3.9 (95% CI, 0.97-15.6;
      P = .055). There was no recurrent thromboembolism in either group. CONCLUSIONS:
      Our results suggest an increased risk of major bleeding in patients with moderate
      renal impairment who receive enoxaparin. Because enoxaparin is frequently used
      and outcomes can be life saving or life threatening, we encourage further study
      of the appropriate dose in patients with moderate renal impairment.

PMID- 23128836
TI  - Hashimoto's encephalopathy as a treatable adult-onset cerebellar ataxia mimicking
      spinocerebellar degeneration.
AB  - BACKGROUND: Hashimoto's encephalopathy (HE) presents with a variety of neurologic
      and neuropsychiatric features. In this study, we investigated the clinical and
      immunological profiles of the cerebellar ataxic form of HE. METHODS: The clinical
      features, treatments, laboratory features, brain imaging, and serum anti-NH(2)
      terminal of alpha-enolase autoantibodies (anti-NAE Abs), a useful diagnostic
      marker for HE, were investigated in 13 patients who presented with sporadic adult
      onset cerebellar ataxia and fulfilled the HE diagnostic criteria (antithyroid Abs
      and responsiveness to immunotherapy). RESULTS: All of the patients presented with
      truncal ataxia, but nystagmus was uncommon (17%). Eight patients had an insidious
      onset that mimicked spinocerebellar degeneration (SCD), but brain imaging showed
      little or no cerebellar atrophy in all of the patients. Those patients with serum
      anti-NAE Abs (n = 8) did not have nystagmus and tended to respond better to
      immunotherapy than the anti-NAE Ab-negative patients. CONCLUSION: The present
      study suggests that insidious adult-onset and truncal ataxia are common in the
      cerebellar ataxic form of HE, which mimics SCD, but that nystagmus and severe
      cerebellar atrophy are uncommon. Antithyroid and anti-NAE Abs may be useful for
      diagnosing cerebellar ataxic HE.

PMID- 23128837
TI  - Shankuan Zhu; editorial board member, EJCN.

PMID- 23128838
TI  - Subacute concussion-related symptoms and postconcussion syndrome in pediatrics.
AB  - PURPOSE OF REVIEW: Millions of youth sustain concussion each year; although most
      fully recover following an isolated concussion, a significant minority develop
      prolonged symptoms and disability following concussion. This article reviews
      recent data regarding the epidemiology of postconcussion syndrome (PCS) and
      recommendations for the evaluation and management of postconcussive symptoms in
      pediatrics. RECENT FINDINGS: PCS is a constellation of symptoms related to head
      injury including somatic symptoms, sleep dysregulation, cognitive deficits and
      emotional disturbance. Postconcussive symptoms affect 1.5-11% of concussed youth
      for more than 1 month after injury, depending on the population studied. Girls
      have a higher risk of postconcussive headache but it is not clear if cognitive
      recovery differs between the sexes. Advanced neuroimaging techniques demonstrate
      a correlation between postconcussive symptoms and functional neurological
      changes. However, pre-existing and psychosocial factors also affect risk for
      prolonged PCS. Current treatment strategies are based mainly on expert opinion
      and studies of related syndromes. SUMMARY: Although a minority of concussed youth
      develop prolonged PCS, those who are affected can develop significant disability.
      Prolonged postconcussive symptoms are likely due to interactions between the
      biological injury, pre-existing risk factors and psychosocial issues. Further
      research is essential to improve outcomes for this vulnerable population.

PMID- 23128839
TI  - Osteochondritis dissecans of the knee in children and adolescents.
AB  - PURPOSE OF REVIEW: Osteochondritis dissecans (OCD) of the knee is a well
      described condition that can cause significant morbidity in children and
      adolescents; timely diagnosis is key to preventing compromise to the articular
      cartilage and maximizing opportunity to perform a restorative procedure. Juvenile
      OCD has a better prognosis than does adult OCD, with higher rates of spontaneous
      healing with conservative treatment. Still, there are certain indications for
      surgical restoration procedures. Controversies arise over when to decide surgical
      procedure and what is the best surgical treatment option in this young
      population. RECENT FINDINGS: Some authors believe nonoperative management should
      be the first-line treatment for stable OCD lesions in children. The only
      consensus in regard to this modality is that, if a patient is truly asymptomatic
      or experiencing low-level symptoms, then the duration of nonoperative treatment
      should be at least 3-6 months before opting for operative treatment. In the case
      of failed nonsurgical management or in the setting of an unstable fragment,
      surgical intervention should be implemented. Recent published data suggest no
      difference in clinical or radiographic outcome when comparing different surgical
      techniques. SUMMARY: OCD of the knee requires a timely diagnosis to maximize
      opportunity to perform a reparative procedure. Indications for surgical treatment
      are based on lesion stability, skeletal maturity, and clinical symptoms.
      Reestablishing the joint surface, improving the blood supply of the fragment,
      rigid fixation, and early motion are primary goals for osteochondral fragment
      preservation. When the fragment is not suitable for preservation, careful
      consideration of defect location and the patient's clinical presentation will
      determine when cartilage restoration procedures should be utilized.

PMID- 23128840
TI  - Thyroid function patterns at Hashimoto's thyroiditis presentation in childhood
      and adolescence are mainly conditioned by patients' age.
AB  - BACKGROUND: There are few studies investigating the factors which may affect
      different biochemical presentations of Hashimoto's thyroiditis (HT) and these are
      frequently based on limited pediatric populations. AIMS: (1) To assess the
      frequency of thyroid function patterns at HT diagnosis in 608 children and
      adolescents, and (2) to analyze the factors that affect thyroid status at
      diagnosis. RESULTS: At presentation, test results showed euthyroidism in 52.1% of
      patients (subgroup A), overt or subclinical hypothyroidism in 41.4%, and overt or
      subclinical hyperthyroidism in 6.5%. The mean age of patients with thyroid
      dysfunctions (subgroup B) was significantly lower than that of subgroup A, and
      the rate of children below 10 years of age was significantly greater in subgroup
      B. Other variables related to thyroid function patterns were prepubertal status;
      association with either Down or Turner syndromes, which correlated with increased
      risk of thyroid dysfunctions, and association with other autoimmune diseases,
      which correlated with decreased risk of thyroid dysfunctions. None of the
      remaining factors analyzed were associated with increased risk of thyroid
      dysfunctions. CONCLUSIONS: Biochemical thyroid function patterns at HT
      presentation in childhood and adolescence are mainly conditioned by patients'
      age.

PMID- 23128841
TI  - Comparison of three methods for the detection of Epstein-Barr virus in Hodgkin's
      lymphoma in paraffin-embedded tissues.
AB  - The percentage rate of Epstein-Barr virus (EBV)-positive cases of Hodgkin's
      lymphoma (HL) ranges between 20 and 70% in various studies worldwide. To further
      explore the definite rate in China, three methods, including immunohistochemistry
      for EBV latent membrane protein 1 (LMP1), in situ hybridization (ISH) for EBV
      encoded RNA (EBER)-1 and polymerase chain reaction (PCR) for EBV BamHI-W
      fragment, were employed to detect EBV in 59 cases of HL in China using paraffin
      embedded tissue samples. Our results revealed that the PCR method presented the
      highest (44/59, 74.6%) detection rate among the three methods. The other two
      methods identified 66.1% (39/59, LMP1) and 67.8% (40/59, EBER1 ISH) EBV-positive
      results, respectively. Three samples were positive for LMP1 but negative when
      using EBER1 ISH, while another four samples were EBER1-positive but LMP1
      negative. Of the four major histopathological subtypes of HL, the lymphocyte
      predominant (LR) subtype is the one most frequently associated with EBV, followed
      by the mixed cellularity (MC), nodular sclerosis (NS) and lymphocyte depletion
      (LD) subtypes. Our results also indicated the seldomly reported fact that EBV
      positive cases in children were more numerous than those of adults with HL. 

PMID- 23128842
TI  - Changes in a nanoparticle's spectroscopic signal mediated by the local
      environment.
AB  - Using a first-principles theoretical model the adsorption of a methyl  radical on
      different sized silver nanoparticles is compared to the adsorption of the same
      radical on model surfaces. Calculations of our structural, dynamical and
      electronic properties indicated that small changes in the local environment will
      lead to small changes in infrared (IR) wavenumbers, but in dramatic changes in
      the IR signal. Our calculations indicate the lower the adsorption site
      coordination, the higher is the signal strength, suggesting that small changes in
      the electronic charge distribution will result in bigger changes in the
      polarizability and hence in the spectroscopic signal intensity. This effect
      explains, among others, the signal magnification observed for nanoparticles in
      surface enhanced Raman spectroscopic (SERS) experiments.

PMID- 23128843
TI  - Mammalian target of rapamycin as a rational therapeutic target for breast cancer
      treatment.
AB  - Therapies directed at endocrine receptors and human epidermal growth factor
      receptor 2 are important treatment options for patients with breast cancer;
      however, drug resistance and subsequent disease progression in patients with
      advanced disease is inevitable. The mammalian target of rapamycin (mTOR) is a key
      regulator of cell growth and proliferation implicated in the cellular processes
      that lead to the uncontrolled growth of cancer cells. Hence, overactivation of
      the mTOR pathway may also represent a key process in the development of
      resistance to these therapies, and interrupting this signaling cascade may
      alleviate resistance and help restore drug sensitivity. A number of agents that
      target the mTOR pathway have shown potent antitumorigenic effects in vitro, and
      several agents have also shown promise in treating patients with breast cancer.
      Everolimus and temsirolimus are the most clinically advanced agents in this
      class, with recent data from the BOLERO-2 study indicating significant benefit
      associated with everolimus when added to endocrine therapy in patients with
      endocrine therapy-resistant disease. In this review, we consider the translation
      of mTOR inhibitors from laboratory studies to large clinical trials, driven by a
      rational understanding of the role of mTOR in the processes that underlie breast
      cancer tumorigenesis.

PMID- 23128844
TI  - Effects of nasal high flow on ventilation in volunteers, COPD and idiopathic
      pulmonary fibrosis patients.
AB  - BACKGROUND: A high flow of air applied by large bore nasal cannulae has been
      suggested to improve symptoms of chronic respiratory insufficiency. In pediatric
      patients, nasal high-flow (nHF) ventilation was similarly effective compared to
      noninvasive ventilation with a face mask. OBJECTIVES: The aim of this study was
      to describe changes in respiratory parameters. METHODS: We measured pressure
      amplitudes during the respiratory cycle and mean pressures in patients with
      idiopathic pulmonary fibrosis (IPF) and COPD. In order to achieve tidal volume
      and minute volume measurements, we used a polysomnography device. Capillary blood
      was taken for blood gas analysis before and after nHF breathing (8 h). RESULTS:
      nHF led to an increase in pressure amplitude and mean pressure in healthy
      volunteers and in patients with COPD and IPF in comparison with spontaneous
      breathing. In COPD, nHF increased tidal volume, while no difference in tidal
      volume was observed in patients with IPF. Interestingly, tidal volume decreased
      in healthy volunteers. Breathing rates and minute volumes were reduced in all
      groups. Capillary pCO2 decreased in patients with IPF and COPD. CONCLUSIONS: nHF
      resulted in significant effects on respiratory parameters in patients with
      obstructive and restrictive pulmonary diseases. The rise in pressure amplitude
      and mean pressure and the decrease in breathing rate and minute volume will
      support inspiratory efforts, helps to increase effectiveness of ventilation and
      will contribute to a reduction in the work of breathing. A CO2 wash-out effect in
      the upper airway part of the anatomical dead space may contribute to the
      beneficial effects of the nHF instrument.

PMID- 23128845
TI  - Mechanochemical synthesis of an yttrium based metal-organic framework.
AB  - For the first time a metal hydride has been used for the preparation of a metal
      organic framework. MIL-78 has been synthesized by the solid-state mechanochemical
      reaction between yttrium hydride and trimesic acid. The process does not involve
      solvents and does not generate liquid by-products, thus proving the viability of
      the solid-state approach to the synthesis of MOFs.

PMID- 23128846
TI  - Does asymptomatic carriage of FV Leiden and FII prothrombin mutations in
      heterozygous configuration pose an increased risk of thrombembolic complications
      in the course of pregnancy, labor and puerperium?
AB  - OBJECTIVE: To evaluate the course of pregnancy and puerperium in asymptomatic
      carriers of FV Leiden and FII prothrombin mutation in heterozygous configuration
      in terms of risk of thrombembolic disease (TED) and late pregnancy complications.
      To evaluate whether global prophylactic LMWH administration during pregnancy
      benefits these women. METHODS: We monitored the incidence of thrombembolic events
      and severe late pregnancy complications in 473 asymptomatic carriers of FV Leiden
      and FII prothrombin mutation in heterozygous configuration. In 253 women,
      preventive LMWH application was introduced already during pregnancy. In 220
      women, the application of LMWH was commenced as late as on the delivery day. In
      both groups application of LMWH continued during the puerperium. RESULTS: The
      incidence of TED in the whole group of carriers of thrombophylic mutations
      accounted for 0.19%. The incidence of severe late pregnancy complications was low
      - 2.5% compared with general population of pregnant women (6.4%). CONCLUSIONS: No
      direct causal relationship was established between asymptomatic carriage of
      Leiden and prothrombin mutation in heterozygous configuration and the occurrence
      of severe late pregnancy complications. There was no benefit from general LMWH
      prophylaxis started as early as pregnancy in these women and thus we consider it
      unnecessary.

PMID- 23128847
TI  - Exercise training combined with electromyostimulation in the rehabilitation of
      patients with chronic heart failure: A randomized trial.
AB  - AIM: Both aerobic training (AT) and electromyostimulation (EMS) of leg muscles
      improve exercise tolerance in patients suffering from chronic heart failure
      (CHF). It was speculated that combination of both methods might have an additive
      effect. This study was performed to evaluate the effects of a combination of AT
      and EMS in rehabilitation (RHB) of CHF patients. PATIENTS AND METHODS: Patients
      (n=71; age 59 +/- 10.2 yrs, NYHA II/III, EF 32 +/- 7.1%) were randomized into 3
      groups: a) group AT, b) group EMS, and c) group AT+EMS. AT protocol included
      standard activity on bicycle 3x a week at the level of individual anaerobic
      threshold. EMS (10 Hz, mode 20s "on"/20s "off") was applied to leg extensors for
      2 h/day. Total time of given type of RHB was 12 weeks. RESULTS: Data analysis
      revealed statistically significant improvements of patients in all experimental
      groups (averaged difference after 12 weeks of exercise as related to initial
      value: ?VO2peak: +12.9%, ?VO2AT: +9.3%, ?Wpeak: +22.7%). No statistically
      significant difference among experimental groups was found. Quality of life
      (Minnesota Living with Heart Failure - MLHF) global score was significantly
      improved in all 3 groups: AT (?MLHF: -27.9%; P=0.001), AT+EMS (?MLHF: -29.1%;
      P=0.002), and EMS (?MLHF: -16.6%; P=0.008). MLHF score in EMS group showed the
      smallest time-related improvement compared to AT and AT+EMS groups, and this
      difference in improvement between the groups was statistically significant
      (P=0.021). CONCLUSION: No significant difference was found between the two types
      of exercise training.and nor did, their combination have any significant
      additional improvement.

PMID- 23128848
TI  - Ischemic preconditioning of the right ventricle: a new application for an old
      concept?.

PMID- 23128850
TI  - Effect of fractionated irradiation on the expression of multidrug resistance
      genes in the CNE1 human nasopharyngeal carcinoma cell line.
AB  - Nasopharyngeal carcinoma (NPC) often develops drug resistance following
      radiotherapy. The molecular basis of radiotherapy-related multidrug resistance
      (MDR) remains unclear. In the present study, we investigated the effect of
      fractionated irradiation on the expression of the MDR-1 gene and the MDR
      associated protein P-glycoprotein (P-gp) in CNE1 human NPC cells. CNE1 cells were
      treated with fractionated X-rays. Drug resistance was determined by MTT assay.
      The expression levels of MDR-1 and P-gp were analyzed by RT-PCR and western blot
      analysis, respectively. Differential expression was analyzed by gene chips. The
      results revealed that low levels of mRNA expression of MDR1 were present in non
      irradiated CNE1 cells. Compared with the control, the expression of MDR1 mRNA was
      gradually increased following fractionated irradiation. On day 21, the expression
      of MDR1 mRNA was increased 1.59- and 2.19-fold, compared with the control, by
      treatment with 10 and 20 Gy, respectively. We observed decreased MDR1 expression
      following treatment with 10 and 20 Gy irradiation on days 28 and 35, compared
      with day 21. On days 21, 28 and 35, expression was increased 1.37-, 1.40- and
      1.15-fold by treatment with 20 Gy compared with 10 Gy. Expression of MDR1 was
      significantly upregulated by treatment with 50 Gy irradiation compared with the
      control on days 78 and 106. P-gp expression was consistent with that of MDR1 mRNA
      expression. The sensitivity of CNE1 cells to cisplatin was reduced following
      irradiation compared with the control. A total of 26 genes were significantly
      upregulated and 8 genes were significantly downregulated compared with the
      control. Results of the present study have shown that MDR1 and P-gp are
      upregulated in CNE1 cells following irradiation. Multiple genes were involved in
      the mechanism of radiation-induced drug resistance. 

PMID- 23128849
TI  - [Patient safety in anesthesiology and intensive care medicine. Measures for
      improvement].
AB  - Technical improvements as well as various strategies for error detection and
      error prevention have made intensive care medicine and anesthesiology a safe
      medical specialty. Due to the introduction of "Patient safety in the ICU: the
      Vienna declaration" of the European Society of Intensive Care Medicine (ESICM)
      from October 2009 and the "Helsinki declaration on patient safety" of the
      European Society of Anaesthesiology (ESA) and the European Board of
      Anaesthesiology (EBA) from June 2010, there are now specific recommendations for
      all hospitals in Europe concerning the safety measures that are considered to be
      of essential importance. Many of today's well-known safety strategies have been
      originally developed in non-medical environments, as for instance civil aviation.
      Such high reliability organizations may serve as examples in the medical domain.
      Critical incident reporting systems, crisis resource management and checklists,
      e.g. the World Health Organization (WHO) checklist, are safety approaches of this
      kind. In addition to these, standardized drug labelling, hand disinfection,
      techniques for patient handover and simulation-based training have been
      exemplarily selected for this article as measures that can increase patient
      safety. 

PMID- 23128851
TI  - Organic salt assisted colloidal synthesis and X-ray luminescence of (Tm, Tb, Eu)
      doped LaOBr nanocrystals.
AB  - The solution-phase synthesis of high quality LaOBr nanocrystals has been realized
      by single source precursors under the assistance of an organic salt (TBAB) and
      characterized by XRD and TEM. The unique crystallization process of LaOBr NCs is
      demonstrated and dictated by the amidation reaction. The X-ray luminescence of
      (Tm, Tb, Eu)-doped LaOBr NCs has also been characterized.

PMID- 23128852
TI  - Dopamine D3 receptor antagonism--still a therapeutic option for the treatment of
      schizophrenia.
AB  - The potential of D(3) receptor antagonism to treat positive, negative, and
      cognitive symptoms of schizophrenia is reviewed on the basis of preclinical
      results and preliminary clinical data. Dopamine D(3) receptors are expressed in
      mesencephalic, limbic, and cortical areas relevant to psychotic and cognitive
      symptoms of schizophrenia. As expected, selective dopamine D(3) receptor
      antagonists are not effective in antipsychotic animal models, reflecting D(2)
      receptor antagonism. However, selective D(3) receptor antagonists affect
      electrical activity of dopamine neurons in the ventral tegmental area similar to
      atypical antipsychotics, counteract effects produced by NMDA glutamate receptor
      blockade, and enhance cortical dopamine and acetylcholine in microdialysis. In
      contrast to dopamine D(2) receptor antagonists, D(3) antagonists positively
      influence a variety of social and cognitive behaviors in rodents, including tests
      representing cognitive flexibility and executive function, which are both
      impaired in schizophrenia patients. Despite considerable affinity for D(3)
      receptors, the second-generation antipsychotics clozapine, risperidone, and
      olanzapine when administered to patients with schizophrenia seem not to occupy
      D(3) receptors sufficiently to derive any conclusion on a D(3)-mediated
      therapeutic benefit. ABT-925, the first selective D(3) receptor antagonist, was
      recently studied in patients with schizophrenia. It produced cognitive signals
      but did not achieve sufficient D(3) receptor occupancy to test the hypothesis
      that D(3) receptor antagonism is of therapeutic value to treat symptoms of
      schizophrenia. Based on mechanistic and experimental considerations and due to
      the fact that D(3) receptor antagonism can inhibit extrapyramidal symptoms and
      produce neither anhedonia nor metabolic adverse effects, the development and
      clinical testing of newer D(3) receptor antagonists with high potency at D(3)
      receptors, enabling sufficient receptor occupancy, is highly warranted.

PMID- 23128855
TI  - Moderate renal impairment and risk of bleeding with anticoagulation.

PMID- 23128853
TI  - Antiulcerogenic activity of chlorogenic acid in different models of gastric
      ulcer.
AB  - Chlorogenic acid (CGA) is found in many foods, including coffee, berries,
      potatoes, carrots, wine, apples, and various herbs, and has anti-inflammatory,
      antidiabetic, and antitumoral actions. The CGA is well absorbed orally, and its
      effects on gastric ulcer have not been previously reported. The present
      manuscript evaluated the effect of oral administration of CGA on ethanol/HCl
      (Et/HCl) or nonsteroidal anti-inflammatory drug (NSAID)-induced gastric ulcer
      model in male Swiss mice. Animals were pretreated with 0.2 %
      carboxymethylcellulose (vehicle, p.o.), omeprazole (positive control, 30 mg/kg,
      p.o.), carbenoxolone (antioxidant positive control, 100 mg/kg, p.o.), or CGA (5,
      25, or 50 mg/kg, p.o.). One hour later, the gastric ulcer was induced by
      injecting Et/HCl solution (100 MUL/10 g body weight; Et 60 % + HCl 0.03 M) or
      piroxicam (100 mg/kg, p.o). After another hour or 4 h later, gastric tissues were
      collected from Et/HCl or piroxicam-treated animals, respectively, to evaluate the
      size of the lesion, histological alterations, secretion of gastric acid,
      neutrophil migration, oxidative/antioxidative enzymes, markers of lipid
      peroxidation, or concentrations of inflammatory mediators. CGA treatment had a
      gastroprotective effect in both models, reducing the percentage of lesioned area.
      CGA treatment did not alter the secretion of gastric action but inhibited
      neutrophil migration and restored the levels of catalase, superoxide dismutase,
      glutathione peroxidase, glutathione, and thiobarbituric acid reactive substances
      in mice treated with Et/HCl. Additionally, CGA treatment blocked the increase of
      tumor necrosis factor alpha and leukotriene B4 but did not restore the reduced
      prostaglandin levels in the NSAID-induced ulcer. Together, the data presented
      herein show that CGA may be a suitable natural compound for the prevention and
      treatment of gastric lesions caused by a different etiology.

PMID- 23128854
TI  - Antiangiogenic role of miR-361 in human umbilical vein endothelial cells:
      functional interaction with the peptide somatostatin.
AB  - Somatostatin (SRIF) acts as antiangiogenic factor, but its role in the regulation
      of microRNAs (miRNAs) targeting proangiogenic factors is unknown. We used human
      umbilical vein endothelial cells (HUVEC) to investigate whether (1) miRNAs
      targeting proangiogenic factors are influenced by hypoxia, (2) their expression
      is regulated by SRIF, and (3) SRIF-regulated miRNAs affect HUVEC angiogenic
      phenotype. The involvement of signal transducer and activator of transcription
      (STAT) 3 and hypoxia inducible factor (HIF)-1 in miRNA effects was studied.
      Quantitative real-time PCR, Western blot, cell proliferation assays, and enzyme
      linked immunosorbent assay (ELISA) were used. Using specific algorithms, three
      miRNAs (miR-17, miR-18b, and miR-361) were predicted to bind angiogenesis
      associated factors including STAT3, HIF-1alpha, and vascular endothelial growth
      factor (VEGF). Hypoxia downregulates miR-17 and miR-361 without affecting miR
      18b. SRIF restored decreased levels of miR-361 acting at the SRIF receptor
      sst(1). Downregulated miR-361 was also restored by HIF-1alpha inhibition with YC
      1. Combined application of SRIF did not influence YC-1-induced miR-361
      downregulation, suggesting that YC-1 and SRIF modulate miR-361 through a common
      mechanism involving HIF-1alpha. This possibility was confirmed by the result that
      HIF-1alpha activation in normoxia-downregulated miR-361 and that this
      downregulation was prevented by SRIF. miR-361 overexpression reduced hypoxia
      induced cell proliferation and VEGF release indicating miR-361 involvement in the
      acquisition of an angiogenic phenotype by HUVEC. miR-361 effects on VEGF were
      enhanced by the coadministration of SRIF. Our results suggest that (1) SRIF
      regulates miR-361 expression through a control on HIF-1, (2) miR-361 affects
      HUVEC angiogenic phenotype, and (3) SRIF and miR-361 act cooperatively in
      limiting hypoxia-induced VEGF release.

PMID- 23128856
TI  - Details of treatment-related difficulties in men with anti-N-methyl-D-aspartate
      receptor encephalitis.
AB  - Anti-N-methyl-D-aspartate receptor (anti-NMDAR) antibody-associated encephalitis
      is an immunologic disease characterized by a female preponderance. Males are
      infrequently affected. The clinical symptoms of affected boys as well as girls
      have been summarized, and they have some clinical features distinct from those of
      adults. However, the characteristics of men have been described in only a few
      reports. We describe in detail four men with anti-NMDAR encephalitis who
      presented with several clinical features that complicated disease management and
      recovery, including venous thrombosis, bilateral hippocampal involvement,
      hypersexuality, and joint contracture. We also report the first detailed clinical
      information about a male patient who died of this disease. In addition, we
      summarize the clinical characteristics of five patients previously reported by
      others.

PMID- 23128857
TI  - Highly diverse TCRalpha chain repertoire of pre-immune CD8+ T cells reveals new
      insights in gene recombination.

PMID- 23128858
TI  - Transition from pediatric to adult healthcare: assessment of specific needs of
      patients with chronic endocrine conditions.
AB  - BACKGROUND/AIM: Transition from pediatric to adult care is a challenging turning
      point. The aim was to evaluate the transition process and needs expressed by
      patients with chronic endocrine conditions at transition in order to ensure
      program optimization. METHODS: Prospective assessment of the transition period
      was conducted through completion of standardized questionnaires given to targeted
      patients. Two types were created: (1) a general questionnaire (GQ) addressing
      universal aspects of transition, and (2) a specific questionnaire (SQ) exploring
      concerns related to each endocrine condition. Three endocrinopathies (congenital
      adrenal hyperplasia, hypogonadotropic hypogonadism and growth hormone deficiency)
      were selected for assessment since they present specific challenges requiring
      characterization. RESULTS: Over the last decade, 244 patients in transition were
      registered in our department and 153 were included since they presented one of
      the endocrinopathies selected. A total of 73 subjects completed both the GQ and
      the SQ. Over 80% of the patients were satisfied with the transition process in
      terms of organization, accessibility and medical care. The actual age of
      transition corresponded for most to the age considered by patients as ideal for
      transition. SQs identified psychosexual issues that must be addressed more
      systematically. CONCLUSION: This study identified key elements allowing the
      creation of an improved transition program tailored for our center and for each
      endocrine condition studied.

PMID- 23128859
TI  - Comparative effectiveness of sulfonylurea and metformin monotherapy on
      cardiovascular events in type 2 diabetes mellitus: a cohort study.
AB  - BACKGROUND: The effects of sulfonylureas and metformin on outcomes of
      cardiovascular disease (CVD) in type 2 diabetes are not well-characterized.
      OBJECTIVE: To compare the effects of sulfonylureas and metformin on CVD outcomes
      (acute myocardial infarction and stroke) or death. DESIGN: Retrospective cohort
      study. SETTING: National Veterans Health Administration databases linked to
      Medicare files. PATIENTS: Veterans who initiated metformin or sulfonylurea
      therapy for diabetes. Patients with chronic kidney disease or serious medical
      illness were excluded. MEASUREMENTS: Composite outcome of hospitalization for
      acute myocardial infarction or stroke, or death, adjusted for baseline
      demographic characteristics; medications; cholesterol, hemoglobin A1c, and serum
      creatinine levels; blood pressure; body mass index; health care utilization; and
      comorbid conditions. RESULTS: Among 253 690 patients initiating treatment (98 665
      with sulfonylurea therapy and 155 025 with metformin therapy), crude rates of the
      composite outcome were 18.2 per 1000 person-years in sulfonylurea users and 10.4
      per 1000 person-years in metformin users (adjusted incidence rate difference, 2.2
      [95% CI, 1.4 to 3.0] more CVD events with sulfonylureas per 1000 person-years;
      adjusted hazard ratio [aHR], 1.21 [CI, 1.13 to 1.30]). Results were consistent
      for both glyburide (aHR, 1.26 [CI, 1.16 to 1.37]) and glipizide (aHR, 1.15 [CI,
      1.06 to 1.26]) in subgroups by CVD history, age, body mass index, and
      albuminuria; in a propensity score-matched cohort analysis; and in sensitivity
      analyses. LIMITATION: Most of the veterans in the study population were white
      men; data on women and minority groups were limited but reflective of the
      Veterans Health Administration population. CONCLUSION: Use of sulfonylureas
      compared with metformin for initial treatment of diabetes was associated with an
      increased hazard of CVD events or death. PRIMARY FUNDING SOURCE: Agency for
      Healthcare Research and Quality and the U.S. Department of Health and Human
      Services.

PMID- 23128862
TI  - Two rotavirus outbreaks caused by genotype G2P[4] at large retirement
      communities: cohort studies.
AB  - BACKGROUND: Outbreaks of rotavirus gastroenteritis in elderly adults are reported
      infrequently but are often caused by G2P[4] strains. In 2011, outbreaks were
      reported in 2 Illinois retirement facilities. OBJECTIVE: To implement control
      measures, determine the extent and severity of illness, and assess risk factors
      for disease among residents and employees. DESIGN: Cohort studies using surveys
      and medical chart abstraction. SETTING: Two large retirement facilities in Cook
      County, Illinois. PATIENTS: Residents and employees at both facilities and
      community residents with rotavirus disease. MEASUREMENTS: Attack rates,
      hospitalization rates, and rotavirus genotype. RESULTS: At facility A, 84 of 324
      residents (26%) were identified with clinical or laboratory-confirmed rotavirus
      gastroenteritis (median age, 84 years) and 11 (13%) were hospitalized. The
      outbreak lasted 7 weeks. At facility B, 90 case patients among 855 residents
      (11%) were identified (median age, 88 years) and 19 (21%) were hospitalized. The
      facility B outbreak lasted 9.3 weeks. Ill employees were identified at both
      locations. In each facility, attack rates seemed to differ by residential
      setting, with the lowest rates among those in more separated settings or with
      high baseline level of infection control measures. The causative genotype for
      both outbreaks was G2P[4]. Some individuals shed virus detected by enzyme
      immunoassay or genotyping reverse transcription polymerase chain reaction for at
      least 35 days. G2P[4] was also identified in 17 of 19 (89%) samples from the
      older adult community but only 15 of 40 (38%) pediatric samples. LIMITATION:
      Medical or cognitive impairment among residents limited the success of some
      interviews. CONCLUSION: Rotavirus outbreaks can occur among elderly adults in
      residential facilities and can result in considerable morbidity. Among older
      adults, G2P[4] may be of unique importance. Health professionals should consider
      rotavirus as a cause of acute gastroenteritis in adults. PRIMARY FUNDING SOURCE:
      None.

PMID- 23128861
TI  - Rescreening of persons with a negative colonoscopy result: results from a
      microsimulation model.
AB  - BACKGROUND: Persons with a negative result on screening colonoscopy are
      recommended to repeat the procedure in 10 years. OBJECTIVE: To assess the
      effectiveness and costs of colonoscopy versus other rescreening strategies after
      an initial negative colonoscopy result. DESIGN: Microsimulation model. DATA
      SOURCES: Literature and data from the Surveillance, Epidemiology, and End Results
      program. TARGET POPULATION: Persons aged 50 years who had no adenomas or cancer
      detected on screening colonoscopy. TIME HORIZON: Lifetime. PERSPECTIVE: Societal.
      INTERVENTION: No further screening or rescreening starting at age 60 years with
      colonoscopy every 10 years, annual highly sensitive guaiac fecal occult blood
      testing (HSFOBT), annual fecal immunochemical testing (FIT), or computed
      tomographic colonography (CTC) every 5 years. OUTCOME MEASURES: Lifetime cases of
      colorectal cancer, life expectancy, and lifetime costs per 1000 persons, assuming
      either perfect or imperfect adherence. RESULTS OF BASE-CASE ANALYSIS: Rescreening
      with any method substantially reduced the risk for colorectal cancer compared
      with no further screening (range, 7.7 to 12.6 lifetime cases per 1000 persons
      [perfect adherence] and 17.7 to 20.9 lifetime cases per 1000 persons [imperfect
      adherence] vs. 31.3 lifetime cases per 1000 persons with no further screening).
      In both adherence scenarios, the differences in life-years across rescreening
      strategies were small (range, 30 893 to 30 902 life-years per 1000 persons
      [perfect adherence] vs. 30 865 to 30 869 life-years per 1000 persons [imperfect
      adherence]). Rescreening with HSFOBT, FIT, or CTC had fewer complications and was
      less costly than continuing colonoscopy. RESULTS OF SENSITIVITY ANALYSIS: Results
      were sensitive to test-specific adherence rates. LIMITATION: Data on adherence to
      rescreening were limited. CONCLUSION: Compared with the currently recommended
      strategy of continuing colonoscopy every 10 years after an initial negative
      examination, rescreening at age 60 years with annual HSFOBT, annual FIT, or CTC
      every 5 years provides approximately the same benefit in life-years with fewer
      complications at a lower cost. Therefore, it is reasonable to use other methods
      to rescreen persons with negative colonoscopy results. PRIMARY FUNDING SOURCE:
      National Cancer Institute.

PMID- 23128863
TI  - Physical therapy interventions for knee pain secondary to osteoarthritis: a
      systematic review.
AB  - BACKGROUND: Osteoarthritis is a leading cause of disability. Nonsurgical
      treatment is a key first step. PURPOSE: Systematic literature review of physical
      therapy (PT) interventions for community-dwelling adults with knee
      osteoarthritis. DATA SOURCES: MEDLINE, the Cochrane Library, the Physiotherapy
      Evidence Database, Scirus, Allied and Complementary Medicine, and the Health and
      Psychosocial Instruments bibliography database. STUDY SELECTION: 193 randomized,
      controlled trials (RCTs) published in English from 1970 to 29 February 2012. DATA
      EXTRACTION: Means of outcomes, PT interventions, and risk of bias were extracted
      to pool standardized mean differences. Disagreements between reviewers
      abstracting and checking data were resolved through discussion. DATA SYNTHESIS:
      Meta-analyses of 84 RCTs provided evidence for 13 PT interventions on pain (58
      RCTs), physical function (36 RCTs), and disability (29 RCTs). Meta-analyses
      provided low-strength evidence that aerobic (11 RCTs) and aquatic (3 RCTs)
      exercise improved disability and that aerobic exercise (19 RCTs), strengthening
      exercise (17 RCTs), and ultrasonography (6 RCTs) reduced pain and improved
      function. Several individual RCTs demonstrated clinically important improvements
      in pain and disability with aerobic exercise. Other PT interventions demonstrated
      no sustained benefit. Individual RCTs showed similar benefits with aerobic,
      aquatic, and strengthening exercise. Adverse events were uncommon and did not
      deter participants from continuing treatment. LIMITATION: Variability in PT
      interventions and outcomes measures hampered synthesis of evidence. CONCLUSION:
      Low-strength evidence suggested that only a few PT interventions were effective.
      Future studies should compare combined PT interventions (which is how PT is
      generally administered for pain associated with knee osteoarthritis). PRIMARY
      FUNDING SOURCE: Agency for Healthcare Research and Quality.

PMID- 23128864
TI  - Drug treatment of asymptomatic hypertriglyceridemia to prevent pancreatitis:
      where is the evidence?

PMID- 23128866
TI  - Cardiovascular effects of diabetes drugs: emerging from the dark ages.

PMID- 23128867
TI  - Colorectal cancer screening: America's next top model?

PMID- 23128868
TI  - In defense of the personal statement.

PMID- 23128869
TI  - Screening women for intimate partner violence.

PMID- 23128871
TI  - Risk for hepatocellular carcinoma in patients with alcoholic cirrhosis.

PMID- 23128872
TI  - Risk for hepatocellular carcinoma in patients with alcoholic cirrhosis.

PMID- 23128874
TI  - Diagnostic problems after change in brand of lubricant jelly.

PMID- 23128875
TI  - Barriers to outpatient respiratory therapy among adult residents of emergency
      shelters.

PMID- 23128878
TI  - Summaries for patients. How do older diabetes drugs compare in their effects on
      heart and blood vessel disease?

PMID- 23128879
TI  - In the clinic. Parkinson disease.

PMID- 23128880
TI  - Combined qualitative and quantitative research designs.
AB  - PURPOSE OF REVIEW: Mixed methods research designs have been recognized as
      important in addressing complexity and are recommended particularly in the
      development and evaluation of complex interventions. This article reports a
      review of studies in palliative care published between 2010 and March 2012 that
      combine qualitative and quantitative approaches. RECENT FINDINGS: A synthesis of
      approaches to mixed methods research taken in 28 examples of published research
      studies of relevance to palliative and supportive care is provided, using a
      typology based on a classic categorization put forward in 1992. SUMMARY: Mixed
      method studies are becoming more frequently employed in palliative care research
      and resonate with the complexity of the palliative care endeavour. Undertaking
      mixed methods research requires a sophisticated understanding of the research
      process and recognition of some of the underlying complexities encountered when
      working with different traditions and perspectives on issues of: sampling,
      validity, reliability and rigour, different sources of data and different data
      collection and analysis techniques.

PMID- 23128881
TI  - Size scaling of mesoporous silica membranes produced by nanosphere mediated laser
      ablation.
AB  - Monodisperse silica nanospheres with sizes ranging from 250 to 725 nm were
      prepared and assembled into monolayers to produce regularly distributed light hot
      spots at the surface of oxidized silicon substrates when illuminated by a laser.
      Single UV nanosecond laser pulses were employed with energies above the local
      ablation threshold for the silicon dioxide layer, resulting in the direct
      formation of 2D periodically porous membranes on top of the silicon. The
      periodicity of the array was driven by the size of the self-assembled
      nanospheres. While the local field enhancement was strongly dependent on the
      sphere size due to Mie resonances, the size and morphology of the produced
      features could be maintained for all tested situations by balancing the change in
      local fields with the laser pulse energy. This work demonstrates the fabrication
      of 90 nm thick porous membranes with pore size of about 100 nm and periodicity
      ranging from 250 to 725 nm.

PMID- 23128882
TI  - Role of CYP1A2 polymorphisms in breast cancer risk in women.
AB  - Cytochrome P4501A2 (CYP1A2) is a key enzyme in the etiology of breast cancer
      (BC). It is involved in breast carcinogen activation [aromatic (AAs) and
      heterocyclic amines (HAs), polycyclic aromatic hydrocarbons (PAHs)], in the
      production of beneficial oestrogen [2-hydroxyestrone (2-OHE1)] and in converting
      arachidonic acid (AAc) to epoxyeicosatrienoic acids (EETs), which have anti
      inflammatory properties. Within a hospital-based case-control study, the effect
      of functional CYP1A2 variants [-3860G/A (rs2069514), -2467T/delT (rs3569413), 
      163C/A (rs762551)] and their interactions with environmental factors in BC risk
      was investigated. The study population included 125 BC cases and 43 non-cancer
      controls. Genotyping was performed in RT-PCR using Taqman assays. The gene
      environment interaction was appraised using a case-only study design. We found
      that the -3860A variant, independently from environmental factors, as well as by
      interacting with fried foods (p=0.025) and indoor exposure to pollutants
      (p=0.050), reduced the risk of BC (p=0.025), whereas its interaction with coffee
      (p=0.045) increased the BC risk. This is the first study indicating that the 
      3860A variant, by decreasing CYP1A2 activity, modifies BC risk by interacting
      with environmental factors, thereby supporting the hypothesis that reduced CYP1A2
      activity contributes to BC risk in different ways, for example, it may be
      protective by reducing the activation of pro-carcinogens such as AAs, HAs and
      PAHs, but would increase risk by reducing the beneficial formation of 2-OHE1 and
      EETs. 

PMID- 23128883
TI  - [Therapeutic response and survival in patients with hairy cell leukemia in a
      third level institution].
AB  - BACKGROUND: in Mexico published casuistry concerning hairy cell leukemia (HCL) is
      limited. OBJECTIVE: to describe the therapeutic response and survival of patients
      with HCL attended in a third level public institution. METHODS: patient's data
      with HCL diagnosis registered between January 1989 - December 2009 were analyzed.
      RESULTS: twenty three patients fulfilled HCL diagnosis criteria. Median age was
      44 years (range 23-75 years) and median follow-up of the cohort was 1,877 days
      (range 1-8,462 days). First line treatment varied along time finding complete
      response (CR) and partial response (PR) rates of 77.3 and 18.2%, respectively. Of
      all therapeutic modalities employed cladribine induced the highest response rate.
      Survival at 1,877 days was 82.6%. At last follow-up 65.2% of patients remain
      alive, 13 in CR and 2 in PR; 4 died (CR = 2, PR = 1, active disease = 1) and 4
      were lost during follow-up. CONCLUSION: this study which included more patients
      than previous single-institution Mexican series confirm the chronic clinical
      behavior of HCL and that purine analogs are corner stone in the treatment of
      patients suffering HCL.

PMID- 23128884
TI  - [Prevalence of cardiovascular risk factors in Balearic workers apparently
      healthy].
AB  - BACKGROUND: the prevalence of cardiovascular risk factors is well known in the
      general population. The aim of our study is to determine the prevalence of
      unknown major cardiovascular risk factors, in an apparently healthy Balearic
      working population. METHOD: data were obtained to 3,035 people randomly selected
      and with unknown previous diagnosis of hypertension, diabetes or
      hypercholesterolemia. To compare proportions we used the chi2 test and the t
      Student test for comparison of means. RESULTS: the prevalence of unknown
      hypertension in men was 20.6%, hypercholesterolemia 11.6%and 2.6% diabetes. The
      prevalence of unknown hypertension, hypercholesterolemia and diabetes in women
      were 8.3,5.4 and 0.8%, respectively. All cardiovascular risk factors except low
      HDL-cholesterol were more prevalent in men. 14.4%of men and 5.5% of women met
      metabolic syndrome. CONCLUSIONS: there is a very high prevalence of
      cardiovascular risk factors in the working population considered theoretically
      healthy. This highlights the important role in this field from the occupational
      health units to make them emerge.

PMID- 23128885
TI  - [Internet social networks tobacco outreach: the clinical experience against
      tobacco of the General Hospital of Mexico "Eduardo Liceaga"].
AB  - Mass communication is essential to social harmony and for the dissemination of
      ideas and ways of life. OBJECTIVE: understanding the impact of social networking
      to complete health communication microblogging and dissemination of tobacco
      control and describe its scope and limitations. METHODS: they opened accounts on
      Facebook and Twitter Wall recording activity, messages and papers presented at
      the January 2010 period through September 2011 in the profiles of both accounts.
      RESULTS: 1,694 there were friends, 707 men and 987 women plus 814 institutions
      and 77 followers Facebook Twitter followers, having both a greater response
      between 20-40 years of age in different social levels, with similar
      characteristics and results of operation as models of counter-advertising to quit
      smoke and effective with good impact on the measures related to treatment and
      harm to health caused by smoking, it was shown that the non-professional
      population has a high interest in these themes. CONCLUSIONS: we suggest that the
      cost-effectiveness of these programs should be evaluated, and improved future
      programs should be considered also for selected universal smoking cessation
      programs indicated by activist via the internet.

PMID- 23128886
TI  - [Study of patients with gout: clinical features in the last 2 years of
      monitoring].
AB  - OBJECTIVE: to analyze the clinical characteristics of gout patients with < 3
      attacks and >= 3 acute attacks per year. METHODS: retrospective observational
      study carried out at 6-primary care (AP) and 2 hospitals. We included patient's
      >= 18 years during the years 2003-2007 inclusive. The study groups were: patients
      with 1-2 and >= 3 attacks/acute recurrences.The main variables: demographic,
      metabolic syndrome (MS), clinical features and treatment. STATISTICAL ANALYSIS:
      logistic regression model, p < 0.05. RESULTS: 3,130 patients were included. The
      mean age was 55.8 years and 81.1% were male:31.6% have >= 3 attacks per year. The
      prevalence of MS was 28.8% (CI: 27.2-30.4%) in patients with 1-2 attacks.
      Subjects with >= 3 acute attacks were associated with: MS (OR: 6.2; CI: 4.6-8.3;
      65.8 vs. 11.8%), obesity (OR: 2.1; CI: 1.7-2.5;63.5 vs. 33.8%) and hypertension
      (OR: 1.6; CI: 1.3-1.9; 58.3 vs. 36.9%), p < 0.001; 58.4% continued to take
      allopurinol(50.3 vs. 62.2%; p < 0.001). CONCLUSIONS: patients with >= 3 attacks
      per year have a more severe disease with acute poly-articular, tophi and higher
      number of co-morbidities. It is important to control uric acid to reduce the
      recurrence of attacks in these patients.

PMID- 23128887
TI  - [Alternative therapies for smoking cessation: clinical practice guidelines
      review].
AB  - BACKGROUND: smoking is a chronic disease in the group of addictions and its
      treatment includes two components:psychosocial and pharmacological intervention.
      Other types of therapeutic approaches have been used as treatment options for
      tobacco addiction. Acupuncture, hypnosis and homeopathy are the most used
      nonconventional interventions. OBJECTIVE: review the available evidence in
      regards to the use of alternative therapies for smoking cessation in the adult
      population from the published clinical practice guidelines (CPG). METHODS: we
      performed an adaptation process of clinical recommendations from a systematic
      review of the literature specifically related to the use of alternative therapies
      for smoking cessation. RESULTS: we found 925 references, 9 were pre-screened and
      selected 5 CPG for adaptation.Acupuncture and related techniques do not improve
      abstinence rates compared to the placebo effect. There is insufficient evidence
      to recommend the use of hypnosis as a therapy for smoking cessation. There is no
      evidence that justifies the use of homeopathic medicines for the treatment of
      smoking. CONCLUSIONS: alternative therapies have not demonstrated efficacy in
      cessation. It is recommended to use other treatment options with proven efficacy
      for smoking cessation.

PMID- 23128888
TI  - [Regulation by histamine H3 receptors of neurotransmitter release in the basal
      ganglia: implications for Parkinson's disease pathophysiology].
AB  - Parkinson's disease is a progressive neurodegenerative movement disorder that
      results primarily from the death of dopaminergic neurons in the substantia nigra
      pars compacta. However, other neurotransmitter systems (noradrenergic,cholinergic
      and serotoninergic) are also involved in the disease. On the other hand, there is
      increasing evidence for a role of histamine as a neuromodulator in the mammalian
      central nervous system. Histamine-releasing neurons are exclusively located in
      the tuberomammilary nucleus of the hypothalamus, project to all major areas of
      the brain and participate in functions such as the regulation of
      sleep/wakefulness, locomotor activity, autonomic and vestibular functions,
      feeding and drinking, analgesia, learning and memory. In this work we review the
      pathophysiological characteristics of Parkinson's disease and the emerging
      information about alterations in histaminergic transmission reported for
      parkinsonian patients and animal models of the disease. In particular, we focus
      on the role of histamine H3 receptors, expressed at high density in the basal
      ganglia, in the normal function of these nuclei and their possible participation
      in the pathophysiology of Parkinson's disease.

PMID- 23128889
TI  - [Primary sclerosing cholangitis presenting as recurrent cholangitis and right
      hepatic duct outpouching].
AB  - Primary sclerosing cholangitis (PSC) may have an atypical mode of presentation
      with recurrent cholangitis and diverticulum-like outpouchings of the hepatic
      ducts; a high clinical suspicion is required to confirm the diagnosis instead of
      ascribing cirrhosis to a secondary cause as a result of the biliary stasis
      propitiated by the biliary cysts. We describe the case of a 63-year old woman
      with a one-year history of episodes of cholangitis and a persistent elevation of
      alkaline phosphatase. The endoscopic retrograde cholangiopancreatography and a
      magnetic resonance cholangiography showed strictures of the intrahepatic biliary
      tract compatible with PSC and a diverticulum-like outpouching of the right
      hepatic duct. A liver biopsy revealed cirrhosis. Initial management consisted of
      antibiotics, a sphincterotomy and the placement of a biliary plastic stent,
      however, the patient continued to have recurrent cholangitis and finally, the
      cyst was resected.

PMID- 23128890
TI  - [An approach to legal and operational issues in the management of health data].
AB  - Data protection regulation is a new and appealing issue in Mexico. The processing
      of health personal data will require even more specific regulation in the near
      future. Health care professionals and institutions need to adequate their usual
      proceedings to comply with the actual regulation in order to protect their
      patients and customers and avoid fines up to 35 million Mexican pesos and 10
      years of prison. The aim of this article is to present a practical approach to
      the legal and managerial implications of this regulation.

PMID- 23128891
TI  - [The Emperor's physician before and after the Empire].
AB  - S. Basch (1837-1905) succeeded F. Semeleder as personal physician to the Mexican
      emperor. The newly appointed imperial physician had been a pupil of Brucke (1819
      1892) in Vienna. After the death of the emperor, Basch returned to Europe, where
      he would study under the guidance of K. Ludwig (1816-1895). Thereafter he
      invented the sphygmomanometer in Berlin.

PMID- 23128892
TI  - Correlation between age, emergency department length of stay and hospital
      admission rate in emergency department patients aged >=70 years.
AB  - BACKGROUND: Interdisciplinary emergency departments (EDs) are confronted with
      trauma and nontrauma patients of any age group. Length of stay (LOS) and
      admission rates reflect both disease complexity and severity. OBJECTIVE: To
      evaluate LOS and admission rates in different age groups according to traumatic
      and nontraumatic etiologies. PATIENTS AND METHODS: During May 2011 a total of
      4,653 adult patients (defined as >=18 years old) seen in the ED of our municipal
      hospital were evaluated for their primary problem, Emergency Severity Index, LOS
      and admission rate. 1,841 trauma patients (mean age: 51.9 years; SD 22.5 years)
      and 2,812 nontrauma patients (mean age: 60.0 years; SD 20.4 years) were included.
      RESULTS: Median LOS in the ED was 1:41 h (trauma) and 1:52 h (nontrauma). Trauma
      patients aged >=70 years spent more time in the ED than nontrauma patients of
      this age group (patients aged >=70 years median: 2:08 vs. 1:56 h; p < 0.0001).
      However, no significant difference was found in patients aged <70 years (1:33 vs.
      1:48 h; p = 0.64). Comparing older with younger patients, median LOS within the
      ED was about 8 min longer in nontrauma patients aged >=70 years (p = 0.22) and
      about 35 min longer in trauma patients aged >=70 years (p < 0.00001).
      CONCLUSIONS: The correlation between age and LOS is stronger for trauma patients,
      which might indicate a special need for geriatric expertise in elderly trauma ED
      patients. Thus an interdisciplinary approach including surgical and geriatric
      expertise may be advantageous.

PMID- 23128893
TI  - Ischemic preconditioning reduces right ventricular infarct size through opening
      of mitochondrial potassium channels.
AB  - OBJECTIVES: We investigated whether ischemic preconditioning (IPC) protects the
      right ventricular (RV) myocardium against ischemic injury in hearts treated with
      the specific mitochondrial ATP-sensitive potassium (K(ATP)) channel blocker 5
      hydroxydecanoate (5-HD). METHODS: Hearts from male Wistar rats (300 g, n = 39)
      were isolated and perfused with Krebs-Henseleit buffer and randomized to no IPC
      (control, n = 16), IPC (n = 16) or IPC preceded by addition of 5-HD (100 uM, n =
      7). IPC consisted of 2 * 5 min of global ischemia followed by 40 min of global
      ischemia and 120 min of reperfusion. The effect of IPC on RV myocardial infarct
      size was evaluated by measurement of the infarct size/area-at-risk ratio
      (RVIS/AAR). Postischemic RV function was evaluated by RV pressures. RESULTS: IPC
      produced a marked decrease in RVIS/AAR (24.4 +/- 8.1 vs. 42.6 +/- 10.6%, p <
      0.0001) and improved hemodynamic recovery of RV contractile function compared
      with the control group. We found no difference in RVIS/AAR (45.2 +/- 4.4 vs. 42.6
      +/- 10.6, p > 0.05) or hemodynamic recovery between IPC + 5-HD and control
      hearts. Blockade of mitochondrial K(ATP) channels by 5-HD abolished the
      cardioprotective response to IPC. CONCLUSION: IPC reduces RV myocardial infarct
      size and improves postischemic RV contractile function in the isolated rat heart,
      possibly through opening of the mitochondrial K(ATP) channel.

PMID- 23128894
TI  - Treatment strategy for superficial pharyngeal squamous cell carcinoma
      synchronously combined with esophageal cancer.
AB  - BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is often synchronously
      accompanied by pharyngeal squamous cell carcinoma (PSCC). However, treatment
      strategies for these synchronous cancers have not been established. AIM: To
      evaluate retrospectively the effects of both chemoradiotherapy (CRT) targeted for
      invasive ESCC on synchronous superficial PSCC and additional endoscopic resection
      (ER) for PSCC. PATIENTS AND METHODS: Screening endoscopy in the pharynx was
      performed in newly diagnosed ESCC patients. CRT combined with 5-fluorouracil (5
      FU) and cisplatin (CDDP) was administered to all patients. The effect on
      superficial PSCC was only evaluated for 5-FU-CDDP chemotherapy that excluded the
      pharynx from the radiation field. When PSCC was remnant or recurrent in patients
      evaluated at complete response (CR) of ESCC, ER was performed on the PSCC.
      RESULTS: Fourteen cases of superficial PSCC (4.0%) were detected in 348 ESCC
      patients. Three PSCC reached CR in 8 ESCC-CR patients, while all 3 lesions
      recurred. No treatment response was found in the remaining 11 PSCC. As a second
      treatment, ER for 8 PSCC was completed in the 8 ESCC-CR patients, with one
      complication due to pneumonia. CONCLUSIONS: Standard 5-FU-CDDP CRT targeted for
      invasive ESCC did not demonstrate a sufficient efficacy for superficial PSCC,
      while ER even for PSCC after chemotherapy was curative.

PMID- 23128895
TI  - Retrospective analysis of linac-based radiosurgery for arteriovenous
      malformations and testing of the Flickinger formula in predicting radiation
      injury.
AB  - BACKGROUND AND PURPOSE: The aim of the study was to validate the use of linac
      based radiosurgery in arteriovenous malformation (AVM) patients and to predict
      complications using an integrated logistic formula (ILF) in comparison with
      clinical outcomes. PATIENTS AND METHODS: The results of radiosurgery in 92 AVM
      patients were examined. All patients were treated with linac-based radiosurgery.
      Of these, 70 patients were followed for 12-45 months (median, 24 months) and were
      analyzed. The treated volume varied from 0.09 to 26.95 cm(3) (median, 2.3 cm(3))
      and the median marginal dose was 20 Gy (range, 10.4-22). The median 12-Gy volume
      was 9.94 cm(3) (range, 0.74-60.09 cm(3)). Patients and lesion characteristics
      potentially affecting nidus obliteration and excellent outcome were evaluated by
      performing a log-rank test and univariate and multivariate analyses. The risk for
      radiation injury (RRI) was calculated with an integrated logistic formula. The
      predictive power of the RRI was assessed by calculating the area under the
      receiver operating characteristic (ROC) curve. RESULTS: Follow-up magnetic
      resonance (MR) angiography revealed complete AVM obliteration in 56 of 70
      patients. The MR angiography confirmed an obliteration rate of 80%. The annual
      hemorrhage rate was 1.4% for the first 2 years after radiosurgery and 0%
      thereafter. The number of patients with an excellent outcome was 48 (68%).
      Factors associated with better obliteration were higher radiation dose to the
      lesion margins [12-Gy volume (V12) >10 cm(3)], small volume, and a Pollock
      Flickinger score less than 1.49; those predicting excellent outcomes were V12<10
      cm(3), small volume, and Pollock-Flickinger score less than 1.49, as determined
      by multivariate analyses. Factors associated with radiation injury were V12>10
      cm(3 )(p=0.03) and volume greater than 2 cm(3) (p=0.001), as determined by a
      univariate analysis. The analyses showed an ROC of 0.66. CONCLUSION: These data
      suggest that linac-based radiosurgery is effective. In terms of obliteration,
      excellent outcomes, and especially radiation injury, V12 and volume should be
      considered. The Flickinger formula seems to be applicable to Novalis-treated
      patients, but long-term follow-up is necessary for definite conclusions.

PMID- 23128896
TI  - Impact of the adaptor protein GIPC1/Synectin on radioresistance and survival
      after irradiation of prostate cancer.
AB  - PURPOSE: Studies have shown that GIPC1/Synectin is an essential adaptor protein
      of receptors that play an important role in cancer progression and therapy
      resistance. This is the first study to explore the role of GIPC1/Synectin in
      radioresistance of prostate cancer and as a possible predictive marker for
      outcome of primary radiation therapy. MATERIALS AND METHODS: The effect of RNA
      interference-mediated GIPC1/Synectin depletion on clonogenic cell survival after
      irradiation with 0, 2, 4, or 6 Gy was assayed in two different GIPC1/Synectin
      expressing human prostate cancer cell lines. The clinical outcome data of 358 men
      who underwent radiotherapy of prostate cancer with a curative intention were
      analyzed retrospectively. Uni- and multivariate analysis was performed of
      prostate-specific antigen recurrence-free survival and overall survival in
      correlation with protein expression in pretreatment biopsy specimens. Protein
      expression was evaluated by standard immunohistochemistry methods. RESULTS: In
      cell culture experiments, no change was detected in radiosensitivity after
      depletion of GIPC1/Synectin in GIPC1/Synectin-expressing prostate cancer cell
      lines. Furthermore, there was no correlation between GIPC1/Synectin expression in
      human pretreatment biopsy samples and overall or biochemical recurrence-free
      survival after radiotherapy in a retrospective analysis of the study cohort.
      CONCLUSION: Our results do not show a predictive or prognostic function of
      GIPC1/Synectin expression for the outcome of radiotherapy in prostate cancer.
      Furthermore, our in vitro results do not support a role of GIPC1 in the cellular
      radiation response. However, the role of GIPC1 in the progression of prostate
      cancer and its precursors should be subject to further research.

PMID- 23128897
TI  - Radiotherapy after radical prostatectomy: immediate or early delayed?
AB  - BACKGROUND: Biochemical recurrence after radical prostatectomy (RP) is associated
      with risk indicators, including Gleason score, preoperative PSA level, tumor
      stage, seminal vesicle invasion, and positive surgical margins. The 5-year
      biochemical progression rate among predisposed patients is as high as 50-70%.
      Post-RP treatment options include adjuvant radiotherapy (ART, for men with
      undetectable PSA) or salvage radiotherapy (SRT, for PSA persisting or re-rising
      above detection threshold). Presently, there are no published randomized trials
      evaluating ART vs. SRT directly. METHODS: Published data on ART and SRT were
      reviewed to allow a comparison of the two treatment approaches. RESULTS: Three
      randomized phase III trials demonstrated an almost 20% absolute benefit for
      biochemical progression-free survival after ART (60-64 Gy) compared to a "wait
      and see" policy. The greatest benefit was achieved in patients with positive
      margins and pT3 tumors. SRT can be offered to patients with elevated PSA after
      RP. In 30-70% of SRT patients, PSA will decrease to an undetectable level, thus
      giving a second curative chance. The rate of side effects for both treatments is
      comparably low. The role of irradiation of pelvic lymph nodes and the additional
      use of hormone therapy and radiation dose are discussed. CONCLUSION: It remains
      unclear whether early SRT initiated after PSA failure is equivalent to ART. Where
      SRT is indicated, it should be started as early as possible.

PMID- 23128898
TI  - Benign painful shoulder syndrome: initial results of a single-center prospective
      randomized radiotherapy dose-optimization trial.
AB  - BACKGROUND AND PURPOSE: To compare the efficacy of two different dose
      fractionation schedules for radiotherapy of patients with benign painful shoulder
      syndrome. PATIENTS AND METHODS: Between February 2006 and February 2010, 312
      consecutive evaluable patients were recruited for this prospective randomized
      trial. All patients received radiotherapy with an orthovoltage technique. One
      radiotherapy course consisted of 6 single fractions in 3 weeks. In case of
      insufficient remission of pain after 6 weeks, a second radiation series was
      performed. Patients were randomly assigned to receive either single doses of 0.5
      or 1.0 Gy. The endpoint was pain reduction. Pain was measured before, right
      after, and 6 weeks after radiotherapy using a visual analogue scale (VAS) and a
      comprehensive pain score (CPS). RESULTS: The overall response rate for all
      patients was 83% directly after and 85% 6 weeks after radiotherapy. The mean VAS
      values before, directly after, and 6 weeks after treatment for the 0.5 and 1.0 Gy
      groups were 56.8 +/- 23.7 and 53.2 +/- 21.8 (p = 0.158), 38.2 +/- 26.1 and 34.0
      +/- 24.5 (p = 0.189), and 33.0 +/- 27.2 and 23.7 +/- 22.7 (p = 0.044),
      respectively. The mean CPS before, directly after, and 6 weeks after treatment
      was 9.7 +/- 3.0 and 9.5 +/- 2.7 (p = 0.309), 6.1 +/- 3.6 and 5.4 +/- 3.6 (p =
      0.096), 5.3 +/- 3.7 and 4.1 +/- 3.7 (p = 0.052), respectively. Despite a slight
      advantage in the VAS analysis for the 1.0 Gy group for delayed response, the CPS
      analysis revealed no statistically significant differences between the two single
      dose trial arms for early (p = 0.652) and delayed response quality (p = 0.380).
      CONCLUSION: Radiotherapy is an effective treatment option for the management of
      benign painful shoulder syndrome. Concerning radiation protection, the dose for a
      radiotherapy series is recommended not to exceed 3-6 Gy.

PMID- 23128899
TI  - Abnormal expression of seven myogenesis-related genes in extraocular muscles of
      patients with concomitant strabismus.
AB  - Hyperplasia or hypoplasia of muscles gradually leads to strabismus. Myogenesis
      related genes are involved in extraocular muscle development, including myogenic
      differentiation 1 (MYOD1), myogenin (MYOG), retinoblastoma 1 (RB1), cyclin
      dependent kinase inhibitor 1A (P21), cyclin-dependent kinase inhibitor 1C (P57),
      insulin-like growth factor 1 (IGF1) and muscle creatine kinase (MCK). This study
      evaluated the expression of the above seven myogenesis-related genes by real-time
      quantitative RT-PCR in 18 resected extrocular muscles of patients with
      concomitant strabismus and 12 normal control muscle samples from one presumably
      healthy male 6 h after sudden mortality. We found that although there was a great
      divergence among the expression levels of 6 myogenesis-related regulatory
      factors, the relative expression patterns were similar in all the normal muscles,
      including the synergistic, antagonistic and yoke muscles. However, their
      expression levels in the 18 diseased extraocular muscles were abnormal; the
      expression levels of all the genes, with the exception of P57, were reduced in
      most of the diseased muscle tissues. These results imply that the abnormal
      expression of these myogenesis-related genes may contribute to concomitant
      strabismus. 

PMID- 23128900
TI  - Directed self-assembly of hetero-nanoparticles using a polymer single crystal
      template.
AB  - Hetero-nanoparticles represent a new class of nanomaterials exhibiting intriguing
      multifunctional and collective properties which could find applications in
      photovoltaics, fuel-cell catalysis, medical imaging and therapy, and electronics.
      In this paper, we report a novel polymer-single-crystal-templating (PSCryT)
      approach for the controllable synthesis of hetero-nanoparticles. 2D polymer
      single crystals are used to direct self-assembly of nanoparticles, yielding
      bicomponent Fe(3)O(4)-Pt, Fe(3)O(4)-Au, SiO(2)-Pt, and SiO(2)-Au and tricomponent
      Fe(3)O(4)-Pt-Au hetero-nanoparticles with fine-tuned structures. The as
      synthesized hetero-nanoparticles possess collective properties derived from the
      interface between different particles. For example, compared with pure Pt
      nanoparticles, Fe(3)O(4)-Pt showed enhanced catalytic activity when used in 4
      nitrophenol reduction reaction. The PSCryT method is simple, versatile and can be
      performed in a rational, step-wise manner under mild synthesis conditions. It
      therefore provides a great opportunity for the development of designer hetero
      nanoparticles targeted for various applications.

PMID- 23128901
TI  - Off-label prescribing in palliative care - a cross-sectional national survey of
      palliative medicine doctors.
AB  - BACKGROUND: Regulatory bodies including the European Medicines Agency register
      medications (formulation, route of administration) for specific clinical
      indications. Once registered, prescription is at clinicians' discretion. Off
      label use is beyond the registered use. While off-label prescribing may, at
      times, be appropriate, efficacy and toxicity data are often lacking. AIM: The aim
      of this study was to document off-label use policies (including disclosure and
      consent) in Australian palliative care units and current practices by palliative
      care clinicians. DESIGN: A national, cross-sectional survey was conducted online
      following an invitation letter. The survey asked clinicians their most frequent
      off-label medication/indication dyads and unit policies. Dyads were classified
      into unregistered, off-label and on-label, and for the latter, whether
      medications were nationally subsidised. SETTING/PARTICIPANTS: All Australian
      palliative medicine Fellows and advanced trainees. RESULTS: Overall, 105
      clinicians responded (53% response rate). The majority did not have policies on
      off-label medications, and documented consent rarely. In all, 236
      medication/indication dyads for 36 medications were noted: 45 dyads (19%) were
      for two unregistered medications, 118 dyads (50%) were for 26 off-label
      medications and 73 dyads (31%) were for 12 on-label medications. CONCLUSIONS: Off
      label prescribing with its clinical, legal and ethical implications is common yet
      poorly recognised by clinicians. A distinction needs to be made between where
      quality evidence exists but registration has not been updated by the
      pharmaceutical sponsor and the evidence has not been generated. Further research
      is required to quantify any iatrogenic harm from off-label prescribing in
      palliative care.

PMID- 23128902
TI  - Individual experiences and impacts of a physiotherapist-led, non-pharmacological
      breathlessness programme for patients with intrathoracic malignancy: a
      qualitative study.
AB  - BACKGROUND: Non-pharmacological breathlessness management programmes have been
      shown to be beneficial in the management of lung cancer-related dyspnoea for more
      than 10 years. What is not so clear is how they work. AIM: To evaluate how
      patients with intrathoracic malignancy (lung cancer or pleural mesothelioma)
      undergoing the non-pharmacological breathlessness management programmes benefited
      from the programme, using a qualitative methodology. DESIGN AND SETTING:
      Consecutive patients completing the programme were invited to be interviewed
      (semi-structured and audio-recorded) about their experiences of the programme,
      what had helped them and how. Interviews were transcribed and analysed using
      interpretative phenomenological analysis. RESULTS: Nine patients were
      interviewed. Seven major themes emerged, they are summarised as follows: (1)
      Mixed prior expectations of the programme, (2) flexibility of delivery and
      additional support needs, (3) physiotherapist attributes and skills in developing
      an effective helping relationship, (4) adoption of new techniques, (5) the
      effects and impact of the programme and new techniques, (6) difficulties and
      barriers to achieving change and (7) facing an uncertain future beyond the
      programme. CONCLUSION: The non-pharmacological breathlessness management
      programme appears to offer a wide range of benefits to patients, including
      improving functional capacity, coping strategies and self-control. Such benefits
      are most likely to be due to a combination of breathing control, activity
      management and the therapist qualities.

PMID- 23128903
TI  - A case report of non-islet cell tumour hypoglycaemia associated with ovarian germ
      cell tumour.
AB  - BACKGROUND: Non-islet cell tumour hypoglycaemia is a rare paraneoplastic
      condition in which tumours secrete a high-molecular-weight precursor of insulin
      like growth factor-II causing hypoglycaemia and can be difficult to identify and
      treat. CASE PRESENTATION: This is the case of a 27-year-old patient from Africa
      with metastatic ovarian yolk sac tumour who presented with hypoglycaemia and was
      subsequently diagnosed with non-islet cell tumour hypoglycaemia. CASE MANAGEMENT:
      Our patient required higher doses of glucocorticosteroids than reported in the
      literature in combination with recombinant growth hormone therapy in order to
      control her hypoglycaemia. CASE OUTCOME: This is the first case of non-islet cell
      tumour hypoglycaemia described in association with a germ-cell tumour. Her
      management required collaboration between the endocrinology team, the palliative
      care team, the acute medicine team and physicians in Africa to enable her safe
      journey home. CONCLUSIONS: This case illustrates the need for awareness among
      general physicians of rare tumour manifestations and the need for
      multidisciplinary input for the optimal management of these patients.

PMID- 23128904
TI  - Why do we want the right to die? A systematic review of the international
      literature on the views of patients, carers and the public on assisted dying.
AB  - BACKGROUND: Assisted dying is legal in four European countries and three American
      states. Elsewhere, particularly in more affluent or mainly Protestant countries,
      it remains controversial. Dominant headlines feature professional (medical,
      legal, religious) arguments versus celebrity campaigners; ordinary people are
      less clearly represented. AIM: To synthesise the international evidence of
      people's views and attitudes towards assisted dying in order to inform current
      debate about this controversial issue. DESIGN: Systematic review and mixed method
      synthesis of qualitative and survey data. DATA SOURCES: Eleven electronic
      databases from inception to October 2011; bibliographies of included studies.
      REVIEW METHODS: Two reviewers independently screened papers and appraised
      quality. Qualitative results were extracted verbatim; survey results were
      summarised in a table. Qualitative data were synthesised using framework methods
      and survey results integrated where they supported, contrasted or added to the
      themes identified. RESULTS: Sixteen qualitative studies and 94 surveys were
      included; many participants considered the immediate relevance of assisted dying
      for them. Themes related to poor quality of life, a good quality of death,
      potential abuse of assisted dying and the importance of individual stance. People
      valued autonomy in death as much as in life. Attitudes were diverse, complex and
      related to definitions of unbearable suffering including physical, psycho-social
      and existential factors and were consistent regardless of social, economic, legal
      and health-care contexts. CONCLUSION: Our review sheds light on ordinary people's
      perspectives about assisted dying, when they are ill or disabled. Unbearable
      suffering is a key construct, and common factors are revealed that lead people to
      ask for help to die. The consistency of international views indicates a mandate
      for legislative and medical systems worldwide to listen and understand this.

PMID- 23128905
TI  - Preferences for end-of-life care: a nominal group study of people with dementia
      and their family carers.
AB  - BACKGROUND: The wishes and preferences of people with dementia should inform
      decisions on future care. However, such decisions are often left to family carers
      and may not reflect those the person with dementia would have made for
      themselves. We know little about what influences agreement between people with
      dementia and their carers. AIM: To explore whether people with dementia and their
      carers were able to generate and prioritise preferences for end-of-life care. We
      examined whether carers influenced the choices made by the persons with dementia.
      DESIGN: Nominal group technique. SETTING/PARTICIPANTS: People with dementia (n =
      6), carers (n = 5) and dyads of people with dementia and carers (n = 6) attending
      memory assessment services. METHODS: Three modified nominal group technique
      groups were conducted in five stages: (1) silent generation of ideas, (2)
      discussion, (3) further generation of ideas, (4) discussion and themeing and (5)
      ranking. The discussions were recorded, transcribed and analysed for thematic
      content using NVIVO8. RESULTS: Quality of care, family contact, dignity and
      respect were ranked as significant themes by all groups. The analysis of
      transcripts revealed three main themes: quality of care, independence and control
      and carer burden. People with dementia had difficulty considering their future
      selves. Carers wanted much control at the end of life, raising issues of assisted
      dying and euthanasia. CONCLUSIONS: Wishes and preferences of people with dementia
      and their family carers may differ. To ensure the wishes of people with dementia
      are respected, their views should be ascertained early in the disease before
      their ability to consider the future is compromised.

PMID- 23128906
TI  - Enantioselective analysis of zopiclone in rat brain by liquid chromatography
      tandem mass spectrometry.
AB  - A new high-performance liquid chromatographic method with triple quadrupole mass
      spectrometry detection was developed and validated for the quantification of
      zopiclone enantiomers in rat brain samples. Zopiclone enantiomers were resolved
      on a CHIRALPAK AD column with a mobile phase consisting of
      acetonitrile/ethanol/methanol (60:20:20, v/v/v) at a flow rate of 1.3 mL min(-1).
      Moclobemide was used as internal standard. The sample treatment procedure was
      carried out employing solid-phase extraction, yielding mean absolute recoveries
      of 89.6 and 91.7% for each zopiclone enantiomer. The validated method showed
      linearity in the range of 0.29-344.8 ng g(-1), with quantification limits of 0.29
      ng g(-1) for both enantiomers. Precision and accuracy were within acceptable
      levels of confidence (<15%). The method was applied in a pilot study of zopiclone
      kinetic disposition in rats. It could be observed that the levels of (+)-(S)
      zopiclone were always higher than those of (-)-(R)-zopiclone, confirming the
      stereoselective disposition of zopiclone.

PMID- 23128907
TI  - Effect of changes in the deuterium content of drinking water on the hydrogen
      isotope ratio of urinary steroids in the context of sports drug testing.
AB  - The hydrogen isotope ratio (HIR) of body water and, therefore, of all
      endogenously synthesized compounds in humans, is mainly affected by the HIR of
      ingested drinking water. As a consequence, the entire organism and all of its
      synthesized substrates will reflect alterations in the isotope ratio of drinking
      water, which depends on the duration of exposure. To investigate the effect of
      this change on endogenous urinary steroids relevant to doping-control analysis
      the hydrogen isotope composition of potable water was suddenly enriched from -50
      to 200 0/00 and maintained at this level for two weeks for two individuals. The
      steroids under investigation were 5beta-pregnane-3alpha,20alpha-diol, 5alpha
      androst-16-en-3alpha-ol, 3alpha-hydroxy-5alpha-androstan-17-one (ANDRO), 3alpha
      hydroxy-5beta-androstan-17-one (ETIO), 5alpha-androstane-3alpha,17beta-diol, and
      5beta-androstane-3alpha,17beta-diol (excreted as glucuronides) and ETIO, ANDRO
      and 3beta-hydroxyandrost-5-en-17-one (excreted as sulfates). The HIR of body
      water was estimated by determination of the HIR of total native urine, to trace
      the induced changes. The hydrogen in steroids is partly derived from the total
      amount of body water and cholesterol-enrichment could be calculated by use of
      these data. Although the sum of changes in the isotopic composition of body water
      was 150 0/00, shifts of approximately 30 0/00 were observed for urinary steroids.
      Parallel enrichment in their HIR was observed for most of the steroids, and none
      of the differences between the HIR of individual steroids was elevated beyond
      recently established thresholds. This finding is important to sports drug testing
      because it supports the intended use of this novel and complementary methodology
      even in cases where athletes have drunk water of different HIR, a plausible and,
      presumably, inevitable scenario while traveling.

PMID- 23128908
TI  - Simultaneous determination of 24 or more acidic and alkaline phytohormones in
      femtomole quantities of plant tissues by high-performance liquid chromatography
      electrospray ionization-ion trap mass spectrometry.
AB  - Phytohormones act at relatively low concentrations as major regulatory factors of
      plant growth and development, and cross talk of phytohormones is currently of
      great interest throughout the plant science community. To meet this demand, a
      method that is capable of simultaneously analyzing diverse plant hormones is
      essential. This paper introduces a high-performance liquid chromatographic
      separation technique coupled with sensitive and selective ion trap mass
      spectrometry to simultaneously determine 24 or more acidic and alkaline
      phytohormones, including auxin, cis- and trans-abscisic acid, 11 cytokinins, and
      10 gibberellins, in a single injection of sample. A binary solid-phase extraction
      using Oasis MCX cartridges for cations and Oasis MAX cartridges for anions was
      used to prepurify more than 24 acidic and alkaline phytohormones from a single
      plant extract. The method showed good linearity for all 24 phytohormones with
      R(2) values ranging from 0.9903 to 0.9997. Limits of detection for most of the
      phytohormones were in the femtomole range with some extending into the sub
      femtomole range. This method was applied to hundreds of plant samples comprising
      different tissues from various plants, including herbaceous, woody climbing, and
      woody plants to demonstrate feasibility and to validate the methodology.

PMID- 23128909
TI  - Fourth EuCheMS Chemistry Congress in Prague, Czech Republic.

PMID- 23128910
TI  - Old and new antirheumatic drugs and the risk of hepatotoxicity.
AB  - Given the high prevalence of the use of medications in daily practice and the
      large number of people taking antirheumatic agents, the risk of drug-drug
      interactions and of hepatotoxicity is of concern. Both old and new compounds show
      such a risk. Nonsteroidal antinflammatory drugs are widely used drugs with
      potential adverse hepatic reactions. Nonsteroidal antinflammatory drugs are
      responsible for an important aliquot of transaminase elevation in the general
      population. Genetic susceptibility to diclofenac hepatotoxicity has promoted the
      knowledge about drug-specific, class-specific reactions. Some drugs
      (sulfasalazine, azathioprine, and leflunomide) may cause acute liver injury,
      whereas other compounds (methotrexate) may cause chronic liver damage as the
      result of the interaction among drug, host and environmental factors. The tumor
      necrosis factor-alpha inhibitor, infliximab, is associated with typical drug
      induced autoimmune hepatitis. Also, the other biological disease-modifying
      antirheumatic drugs are not free of potential hepatotoxicity. The diagnosis of
      drug-induced liver injury follows the exclusion of other causes, involves a
      temporal relationship between drug exposure and adverse event, and should
      consider the potential participation of the underlying rheumatic disease to event
      occurrence. This article also includes data regarding hepatotoxicity from our
      outclinic patients receiving biological disease-modifying antirheumatic drugs.

PMID- 23128911
TI  - Detection and validated quantification of the phosphodiesterase type 5 inhibitors
      sildenafil, vardenafil, tadalafil, and 2 of their metabolites in human blood
      plasma by LC-MS/MS--application to forensic and therapeutic drug monitoring
      cases.
AB  - INTRODUCTION: Phosphodiesterase type 5 inhibitors such as sildenafil, vardenafil,
      and tadalafil are a class of drugs used primarily in the treatment of erectile
      dysfunction. Sildenafil and tadalafil are also approved for the treatment of
      pulmonary hypertension. The aim of this study was to develop and validate a
      procedure for the detection and quantification of these 3 drugs and some of their
      metabolites in human blood plasma. METHODS: After liquid-liquid extraction of 0.5
      mL of blood plasma using diethyl ether-ethyl acetate (1:1), the analytes
      sildenafil, norsildenafil, vardenafil, norvardenafil, and tadalafil were
      separated using a Shimadzu Prominence High-Performance Liquid Chromatography
      System (C18 separation column, gradient elution, and a total flow of 0.5 mL/min).
      They were detected using an AB Sciex 3200 Q-Trap LC-MS-MS System (electrospray
      ionization and multiple reaction monitoring mode). The method was fully validated
      according to international guidelines. RESULTS: The assay was found to be
      selective for the tested compounds. It was linear from 5 to 1000 ng/mL for
      sildenafil, from 2 to 700 ng/mL for norsildenafil, from 0.5 to 350 ng/mL for
      vardenafil, from 0.5 to 200 ng/mL for norvardenafil, and from 5 to 1000 ng/mL for
      tadalafil. The recoveries were generally more than 50%. Matrix effects were not
      observed. Accuracy, repeatability, and intermediate precision were within the
      required limits (<15% or <20% near the limit of quantification). No instability
      was observed after repeated freezing and thawing or in processed samples.
      CONCLUSIONS: A liquid chromatography-tandem mass spectrometry assay for the
      determination of sildenafil, norsildenafil, vardenafil, norvardenafil, and
      tadalafil in human blood plasma was developed and validated. It has proven to be
      selective, linear, accurate, and precise for all studied drugs. The method has
      also proven to be applicable for forensic cases and for therapeutic drug
      monitoring.

PMID- 23128912
TI  - Enhanced alcohol electrocatalysis with the introduction of magnetic composites
      into nickel electrocatalysts.
AB  - The addition of a magnetic composite membrane to a traditional nickel
      electrocatalyst was employed to increase the methanol and n-butanol
      electrocatalysis in alkaline media.

PMID- 23128914
TI  - Community health workers combat readmission.

PMID- 23128913
TI  - Infectious diseases causing diffuse alveolar hemorrhage in immunocompetent
      patients: a state-of-the-art review.
AB  - Diffuse alveolar hemorrhage (DAH) represents a syndrome that can complicate many
      clinical conditions and may be life-threatening, requiring prompt treatment. It
      is recognized by the signs of acute- or subacute-onset cough, hemoptysis, diffuse
      radiographic pulmonary infiltrates, anemia, and hypoxemic respiratory distress.
      DAH is characterized by the accumulation of intra-alveolar red blood cells
      originating most frequently from the alveolar capillaries. It must be
      distinguished from localized pulmonary hemorrhage, which is most commonly due to
      chronic bronchitis, bronchiectasis, tumor, or localized infection. Hemoptysis,
      the major sign of DAH, may develop suddenly or over a period of days to weeks;
      this sign may also be initially absent, in which case diagnostic suspicion is
      established after sequential bronchoalveolar lavage reveals worsening red blood
      cell counts. The causes of DAH can be divided into infectious and noninfectious,
      the latter of which may affect immunocompetent or immunodeficient patients.
      Pulmonary infections are rarely reported in association with DAH, but they should
      be considered in the diagnostic workup because of the obvious therapeutic
      implications. In immunocompromised patients, the main infectious diseases that
      cause DAH are cytomegalovirus, adenovirus, invasive aspergillosis, Mycoplasma,
      Legionella, and Strongyloides. In immunocompetent patients, the infectious
      diseases that most frequently cause DAH are influenza A (H1N1), dengue,
      leptospirosis, malaria, and Staphylococcus aureus infection. Based on a search of
      the PubMed and Scopus databases, we review the infectious diseases that may cause
      DAH in immunocompetent patients.

PMID- 23128915
TI  - painDETECT questionnaire and lumbar epidural steroid injection for chronic
      radiculopathy.
AB  - BACKGROUND: The painDETECT questionnaire (PD-Q) is a fast and uncomplicated way
      to ascertain the percentage of neuropathic pain in 'total pain' and is designed
      to detect neuropathic pain components in back pain. The purpose of this
      randomized, prospective study is to compare, with the assessment of the PD-Q, the
      efficacy of interlaminar (IL) and transforaminal (TF) steroid injections in
      patients with unilateral chronic lumbar radicular pain. METHODS: Patients were
      treated fluoroscopically with epidural steroids, using the IL or TF method and
      with confirmation of the epidural space by contrast, using random computerized
      classification. The patients received a series of three IL or TF epidural steroid
      injections (ESI) at 2-week intervals. The patients were monitored for 6 months
      from the first steroid injection. RESULTS: By analyzing the average values of the
      total sum of points in the PD-Q a dropping trend is confirmed for both groups.
      The trend equation (y = -1.1393x + 25.269) for the TF ESI shows a faster recovery
      than the IL ESI (y = -0.8089x + 26.654). The statistically significant difference
      in the two groups is proved between the first and the sixth visit (IL ESI, p =
      0.014; TF ESI, p = 0.001). There is no statistically significant difference in
      the efficiency of the two dosages and the volumes of steroids between the IL and
      TF distribution of steroids. CONCLUSIONS: Steroids are efficient; besides
      alleviating the overall pain, they also reduce the neuropathic component in
      chronic lumbar radicular pain, whether it is distributed epidurally by the IL or
      TF approach.

PMID- 23128916
TI  - Dispelling the "they'll grow out of it" myth: implications for intervention.

PMID- 23128917
TI  - Prenatal exposure to antidepressants: how safe are they?

PMID- 23128918
TI  - Late-life depression research: lessons learned from the metabolic syndrome.

PMID- 23128919
TI  - New insights into BDNF signaling: relevance to major depression and
      antidepressant action.

PMID- 23128920
TI  - Goodbye to the handwritten note.

PMID- 23128921
TI  - Skin picking disorder.
AB  - Although skin picking has been documented in the medical literature since the
      19th century, only now is it receiving serious consideration as a DSM psychiatric
      disorder in discussions for DSM-5. Recent community prevalence studies suggest
      that skin picking disorder appears to be as common as many other psychiatric
      disorders, with reported prevalences ranging from 1.4% to 5.4%. Clinical
      evaluation of patients with skin picking disorder entails a broad physical and
      psychiatric examination, encouraging an interdisciplinary approach to evaluation
      and treatment. Approaches to treatment should include cognitive-behavioral
      therapy (including habit reversal or acceptance-enhanced behavior therapy) and
      medication (serotonin reuptake inhibitors, N-acetylcysteine, or naltrexone).
      Based on clinical experience and research findings, the authors recommend several
      management approaches to skin picking disorder.

PMID- 23128922
TI  - Psychiatric disorders in preschoolers: continuity from ages 3 to 6.
AB  - OBJECTIVE: Recent studies indicate that many preschoolers meet diagnostic
      criteria for psychiatric disorders. However, data on the continuity of these
      diagnoses are limited, particularly from studies examining a broad range of
      disorders in community samples. Such studies are necessary to elucidate the
      validity and clinical significance of psychiatric diagnoses in young children.
      The authors examined the continuity of specific psychiatric disorders in a large
      community sample of preschoolers from the preschool period (age 3) to the
      beginning of the school-age period (age 6). METHOD: Eligible families with a 3
      year child were recruited from the community through commercial mailing lists.
      For 462 children, the child's primary caretaker was interviewed at baseline and
      again when the child was age 6, using the parent-report Preschool Age Psychiatric
      Assessment, a comprehensive diagnostic interview. The authors examined the
      continuity of DSM-IV diagnoses from ages 3 to 6. RESULTS: Three-month rates of
      disorders were relatively stable from age 3 to age 6. Children who met criteria
      for any diagnosis at age 3 were nearly five times as likely as the others to meet
      criteria for a diagnosis at age 6. There was significant homotypic continuity
      from age 3 to age 6 for anxiety, attention deficit hyperactivity disorder (ADHD),
      and oppositional defiant disorder, and heterotypic continuity between depression
      and anxiety, between anxiety and oppositional defiant disorder, and between ADHD
      and oppositional defiant disorder. CONCLUSIONS: These results indicate that
      preschool psychiatric disorders are moderately stable, with rates of disorders
      and patterns of homotypic and heterotypic continuity similar to those observed in
      samples of older children.

PMID- 23128923
TI  - Neurodevelopment of children following prenatal exposure to venlafaxine,
      selective serotonin reuptake inhibitors, or untreated maternal depression.
AB  - OBJECTIVE: Effects on child neurodevelopment of neurotransmitter reuptake
      inhibitors used as antidepressants during pregnancy have not been adequately
      studied. The authors compared the effects of prenatal exposure to venlafaxine
      (serotonin-norepinephrine reuptake inhibitor), selective serotonin reuptake
      inhibitors (SSRIs), and maternal depression. METHOD: A cohort derived from a
      prospectively collected database included four groups of children born to 1)
      depressed women who took venlafaxine during pregnancy (N=62), 2) depressed women
      who took SSRIs during pregnancy (N=62), 3) depressed women who were untreated
      during pregnancy (N=54), and 4) nondepressed, healthy women (N=62). The
      children's intelligence and behavior outcomes were evaluated with standardized
      instruments at one time point between the ages of 3 years and 6 years, 11 months.
      RESULTS: The children exposed to venlafaxine, SSRIs, and maternal depression
      during pregnancy had similar full-scale IQs (105, 105, and 108, respectively).
      The IQs of the venlafaxine and SSRI groups were significantly lower than that of
      the children of nondepressed mothers (112). The three groups exposed to maternal
      depression had consistently, but nonsignificantly, higher rates of most
      problematic behaviors than the children of nondepressed mothers. Severity of
      maternal depression in pregnancy and at testing predicted child behavior.
      Maternal IQ and child sex predicted child IQ. Antidepressant dose and duration
      during pregnancy did not predict any cognitive or behavioral outcome.
      CONCLUSIONS: Factors other than antidepressant exposure during pregnancy strongly
      predict children's intellect and behavior. Depression during pregnancy is a
      significant risk factor for postpartum depression. Children of depressed mothers
      may be at risk of future psychopathology.

PMID- 23128925
TI  - Transcranial stimulation for psychosis: the relationship between effect size and
      published findings.

PMID- 23128926
TI  - Suicide attempt as the presenting symptom of C9orf72 dementia.

PMID- 23128924
TI  - Brain-derived neurotrophic factor signaling and subgenual anterior cingulate
      cortex dysfunction in major depressive disorder.
AB  - OBJECTIVE: The subgenual anterior cingulate cortex is implicated in the pathology
      and treatment response of major depressive disorder. Low levels of brain-derived
      neurotrophic factor (BDNF) and reduced markers for GABA function, including in
      the amygdala, are reported in major depression, but their contribution to
      subgenual anterior cingulate cortex dysfunction is not known. METHOD: Using
      polymerase chain reaction, we first assessed the degree to which BDNF controls
      mRNA expression (defined as BDNF dependency) of 15 genes relating to GABA and
      neuropeptide functions in the cingulate cortex of mice with reduced BDNF function
      (BDNF-heterozygous [Bdnf(+/-)] mice and BDNF exon-IV knockout [Bdnf(KIV)] mice).
      Gene expression was then quantified in the subgenual anterior cingulate cortex of
      51 postmortem subjects with major depressive disorder and comparison subjects
      (total subjects, N=102; 49% were women) and compared with previous amygdala
      results. RESULTS: Based on the results in Bdnf(+/-) and Bdnf(KIV) mice, genes
      were sorted into high, intermediate, and no BDNF dependency sets. In postmortem
      human subjects with major depression, BDNF receptor (TRKB) expression, but not
      BDNF, was reduced. Postmortem depressed subjects exhibited down-regulation in
      genes with high and intermediate BDNF dependency, including markers of dendritic
      targeting interneurons (SST, NPY, and CORT) and a GABA synthesizing enzyme
      (GAD2). Changes extended to BDNF-independent genes (PVALB and GAD1). Changes were
      greater in men (potentially because of low baseline expression in women),
      displayed notable differences from prior amygdala results, and were not explained
      by demographic or clinical factors other than sex. CONCLUSIONS: These parallel
      human/mouse analyses provide direct (low TRKB) and indirect (low expression of
      BDNF-dependent genes) evidence in support of decreased BDNF signaling in the
      subgenual anterior cingulate cortex in individuals with major depressive
      disorder, implicate dendritic targeting GABA neurons and GABA synthesis, and,
      together, suggest a common BDNF-/GABA-related pathology in major depression with
      sex- and brain region-specific features.

PMID- 23128927
TI  - Bipolar disorder and a history of suicide attempts with a duplication in 5HTR1A.

PMID- 23128935
TI  - The atomic layer deposition array defined by etch-back technique: a new method to
      fabricate TiO2 nanopillars, nanotubes and nanochannel arrays.
AB  - A novel fabrication method for nanostructures made of TiO(2), a hard-to-etch
      material with very attractive optical, physical and chemical properties, is
      developed. This technique 'atomic layer deposition array defined by etch-back'
      (AARDE) enables the formation of a large area of perfectly ordered, high aspect
      ratio nanostructures, such as nanopillars, nanotubes and nanochannels. High
      quality functional surfaces and versatile structures with tunable dimensions on
      various substrates can be realized. With all the process steps being controllable
      and compatible with integrated circuits, high throughput and repeatability are
      achieved. To demonstrate the potential of this new technique, results for AARDE
      TiO(2) nanopillar arrays as photonic crystals are also reported.

PMID- 23128934
TI  - The development of a Functional Assessment of Cancer Therapy (FACT) questionnaire
      to assess dermatologic symptoms associated with epidermal growth factor receptor
      inhibitors (FACT-EGFRI-18).
AB  - PURPOSE: Dermatologic toxicities from epidermal growth factor receptor inhibitors
      (EGFRIs) are common, disrupt health-related quality of life (HRQL), and lead to
      dose reduction or discontinuation of potentially life-saving cancer therapy. The
      Functional Assessment of Cancer Therapy (FACT)-EGFRI was developed to measure
      HRQL among patients receiving EGFRIs. METHODS: The FACT-EGFRI was developed
      through the triangulation approach using the established functional assessment of
      chronic illness therapy method of patient questionnaire construction. This
      included literature review, qualitative data collection and analysis, and
      quantitative survey data collection on candidate items to identify the most
      important items related to EGFRI-induced dermatologic toxicities according to
      patients receiving EGFRIs and expert clinicians. RESULTS: Twelve expert
      clinicians and 20 patients were interviewed for the initial questionnaire
      development. Dermatologic symptoms associated with epidermal growth factor
      receptor inhibitors endorsed as high priority by both patients and oncologist
      experts were selected. The final version includes 18 items which assess the
      physical, emotional, social, and functional impact that skin, nail, and hair
      toxicities have on patients' HRQL. CONCLUSIONS: The FACT-EGFRI-18 measures the
      severity of patient-reported EGFRI-induced dermatologic toxicities and effects on
      HRQL and was developed using qualitative data from patients and expert
      clinicians. Further validation is underway. The FACT-EGFRI-18 may be useful for
      clinicians and researchers to quantify dermatologic toxicities from the patient
      perspective in standard clinical care, evaluate the effectiveness of
      interventions to prevent or reduce dermatologic toxicities, and to guide
      treatment decision making.

PMID- 23128936
TI  - Log cabins and lab coats.

PMID- 23128937
TI  - Effects on body composition of different short-term rehabilitation programs in
      long-stay hospitalized elderly women.
AB  - BACKGROUND AND AIMS: Long-stay hospitalized elderly women usually reduce daily
      living activities: this may lead to an accelerated worsening of body composition,
      cardio-metabolic condition and falls risk. Exercise training and electrical
      stimulation may ameliorate such condition. METHODS: The effects of 3 different
      short-term rehabilitation programs on lower limbs (kinesitherapy [KT], electrical
      stimulation [ES], KT combined with ES [KT+ES], 3 day/week for 6 weeks) were
      assessed on 40 hospitalized elderly women (82+/-7 yrs, 59.5+/-12.3 kg, 152+/-7 cm
      [m+/-SD]; n=10 for each intervention group and n=10 as control subjects [no
      intervention]). Segmental (upper and lower limbs) and total body fat mass (FM),
      fat free mass (FFM), bone mineral content (BMC) and density (BMD), resting energy
      expenditure (REE), maximum voluntary force (MVC) of leg extensor muscles and
      cardiorespiratory performance (6-min walking test [6MVT]) were evaluated before
      and after intervention. RESULTS: Compared to baseline, the distance covered by
      the 6MWT significantly increased after all rehabilitation programs (from 247+/-79
      to 271+/-87 m, p<0.01), whereas significant increases in leg extensor muscles MVC
      were found after ES (+26%) and KT+ES (+16%) only, p<0.05. No changes in segmental
      and total body FM, FFM and REE were observed, whereas legs BMC significantly
      increased (2.7%) after KT only (p<0.05). CONCLUSIONS: Although all treatments
      increased cardiorespiratory performance, and KT and ES ameliorated muscle force,
      the proposed short-term exercise programs had poor effects on body composition.
      This suggests that longer programs, maybe combined with a tailored dietary
      intervention, should be administered to improve body composition in
      rehabilitating institutionalized elderly people.

PMID- 23128938
TI  - Effects of IL-1beta on the proliferation and apoptosis of gastric epithelial
      cells and acid secretion from isolated rabbit parietal cells.
AB  - The aim of the present study was to explore the effects of IL-1beta on the
      proliferation and apoptosis of gastric epithelial cells and acid secretion from
      isolated rabbit parietal cells. The mechanisms by which these effects are
      mediated were also investigated. Parietal cells were isolated from rabbit gastric
      mucosa by elutriation. The AGS human gastric cancer cell line, the GES-1 human
      gastric epithelial cell line and parietal cells were treated with interleukin
      (IL)-1beta in the presence or absence of Helicobacter pylori (H. pylori) for the
      times indicated. MTT assay and flow cytometry (FCM) were used to determine the
      levels of proliferation and apoptosis. The expression levels of cyclooxygenase-2
      (COX-2) mRNA and protein were examined by RT-PCR and FCM. Acid secretion by
      parietal cells was examined using 14C-aminopyrine (14C-AP) accumulation.
      H+/K+ATPase alpha subunit mRNA expression was assessed by RT-PCR. The results
      demonstrated that IL-1beta (10 ng/ml) stimul-ated cellular proliferation and
      inhibited H. pylori-induced apoptosis in GES-1 and AGS cell lines. IL-1beta (10
      ng/ml) upregulated the mRNA and protein expression of COX-2 in GES-1 and AGS
      cells. Acid secretion stimulated by histamine was identified as significantly
      inhi-bited and mRNA expression of H+/K+ATPase alpha subunit was downregulated by
      treatment with IL-1beta (10 ng/ml) for 30 min and 16 h compared with the control
      in isolated rabbit parietal cells. The present study demonstrates that IL-1beta
      plays a significant role in H. pylori-induced gastric carcinogenesis through 2
      main mechanisms: i) IL-1beta may interfere in gastric epithelial cell growth by
      upregulating COX-2 expression; ii) IL-1beta may inhibit the acid secretion from
      parietal cells by downregulating H+/K+ATPase expression. 

PMID- 23128939
TI  - Cytoreductive surgery and intraoperative administration of paclitaxel-loaded
      expansile nanoparticles delay tumor recurrence in ovarian carcinoma.
AB  - BACKGROUND: Locoregional recurrence significantly impacts survival and quality of
      life in patients with ovarian carcinoma. We hypothesize that local administration
      of paclitaxel-loaded expansile nanoparticles (pax-eNP) at the time of
      cytoreductive surgery decreases local tumor recurrence. METHODS: In vitro
      cytotoxicity of pax-eNP was assessed against both the OVCAR-3 human ovarian
      cancer cell line and tumor cells isolated from a malignant pleural effusion from
      a patient with multidrug-resistant ovarian cancer. A murine xenogenic model
      involving surgical cytoreduction of established OVCAR-3 intra-abdominal tumor was
      used to evaluate in vivo efficacy of intraoperative intraperitoneal (IP)
      injection of 10 mg/kg of paclitaxel either as pax-eNP or paclitaxel in Cremophor
      EL/ethanol solution (pax-C/E) versus empty eNP controls. Cytoreductive surgery
      and intraoperative treatment were performed 4 weeks after established tumor. All
      animals were sacrificed when empty eNP controls displayed extensive evidence of
      disease progression. RESULTS: Labeled-eNP entered tumor cells in vitro within 4 h
      and specifically accumulated at sites of tumor in vivo. Pax-eNP exhibited dose
      dependent cytotoxicity in both OVCAR-3 and patient tumor cells isolated from a
      malignant pleural effusion and effectively prevented tumor recurrence following
      debulking (p = 0.003 vs. empty eNP). Furthermore, pax-eNP-treated animals did not
      develop severe recurrent carcinomatosis compared with 43 % of the pax-C/E-treated
      cohort, suggesting that single-dose intracavitary pax-eNP is more effective than
      an equivalent dose of pax-C/E. CONCLUSIONS: Expansile nanoparticles readily enter
      human ovarian tumor cells and localize to sites of tumor in vivo with pax-eNP
      cytotoxicity resulting in superior inhibition of locoregional tumor recurrence
      following cytoreductive surgery.

PMID- 23128940
TI  - Free flap reconstruction after robot-assisted neck dissection via a modified face
      lift or retroauricular approach.
AB  - BACKGROUND: We performed robot-assisted neck dissection (RAND) via a modified
      face-lift (MFLA) or retroauricular approach for neck management and carried out
      free flap reconstruction via these approaches in patients with head and neck
      cancer. We assessed the feasibility of free flap reconstruction in patients who
      had undergone transoral resection of a primary lesion and RAND via these
      approaches. METHODS: In this prospective study, seven patients with head and neck
      squamous cell carcinoma were enrolled between August 2011 and May 2012. Approval
      was obtained from the institutional review board of Yonsei University. A radial
      forearm free flap was used for reconstruction because of its thin structure and
      pliability. Microvascular anastomosis was performed via an MFLA or retroauricular
      approach using a microscope and microvascular instrument set. RESULTS: Pathology
      reports showed a negative margin in all patients. On the basis of pathologic
      information for the primary lesion and neck specimens, 5 patients underwent
      surgery alone and two received adjuvant radiotherapy. At the last outpatient
      department visit, all patients were alive without locoregional recurrence. All
      patients were extremely satisfied with the invisible postoperative scar. On
      average, patients tolerated an oral diet after 1-2 weeks. The status of the free
      flap was viable and functioning in all patients. CONCLUSIONS: Although long-term
      follow-up of oncologic safety is required to establish these approaches as valid
      treatment methods, our study has demonstrated the feasibility of free flap
      reconstruction and RAND via an MFLA or retroauricular approach.

PMID- 23128941
TI  - Irreversible electroporation in locally advanced pancreatic cancer: potential
      improved overall survival.
AB  - BACKGROUND: Locally advanced unresectable pancreatic adenocarcinoma (LAC) is
      characterized by poor survival despite chemotherapy and conventional radiation
      therapy. We have recently reported on the safety of using irreversible
      electroporation (IRE) for the management of LAC. The purpose of this study was to
      evaluate the overall survival in patients with LAC treated with IRE. METHODS: A
      prospective, multi-institutional evaluation of 54 patients who underwent IRE for
      unresectable pancreatic cancer from December 2009 to October 2010 was evaluated
      for overall survival and propensity matched to 85 matched stage III patients
      treated with standard therapy defined as chemotherapy and radiation therapy
      alone. RESULTS: A total of 54 LAC patients have undergone IRE successfully, with
      21 women, 23 men (median age, 61 (range, 45-80) years). Thirty-five patients had
      pancreatic head primary and 19 had body tumors; 19 patients underwent margin
      accentuation with IRE and 35 underwent in situ IRE. Forty-nine (90 %) patients
      had pre-IRE chemotherapy alone or chemoradiation therapy for a median duration 5
      months. Forty (73%) patients underwent post-IRE chemotherapy or chemoradiation.
      The 90 day mortality in the IRE patients was 1 (2 %). In a comparison of IRE
      patients to standard therapy, we have seen an improvement in local progression
      free survival (14 vs. 6 months, p = 0.01), distant progression-free survival (15
      vs. 9 months, p = 0.02), and overall survival (20 vs. 13 months, p = 0.03).
      CONCLUSIONS: IRE ablation of locally advanced pancreatic tumors remains safe and
      in the appropriate patient who has undergone standard induction therapy for a
      minimum of 4 months can achieve greater local palliation and potential improved
      overall survival compared with standard chemoradiation-chemotherapy treatments.
      Validation of these early results will need to be validated in the current multi
      institutional Phase 2 IDE study.

PMID- 23128942
TI  - [Highlights of the XXII Congress of the Latinoamerican Association for the Study
      of the Liver].

PMID- 23128943
TI  - [Early prediction of severity in acute pancreatitis].
AB  - OBJECTIVE: To identify the score that best predicts early severity in patients
      with acute pancreatitis. MATERIALS AND METHODS: A prospective cohort study was
      performed from December 2009 to December 2011. Cases of pancreatitis were
      classified as mild or severe based on the organ failure criteria and/or local
      complications according to the Atlanta Symposium. APACHE-II, BISAP and urea were
      calculated using data from the first 24 hours. Ranson was calculated using data
      from the first 48 hours. Hemoconcentration was assessed 24 hours from admission,
      after adequate hydration. To assess the predictive value of the different scores
      the area under the curve ROC was used. RESULTS: 329 patients with acute
      pancreatitis were included: 214 women (65%) and 115 males (35%). The most common
      etiology was biliary 245 (74.3%). Two hundred and forty were mild cases of
      pancreatitis (73%) and 89 were severe (27%). The areas under the curve ROC were:
      APACHE-II: 0.74; BISAP: 0.78; Ranson: 0.48; urea: 0.70; hemoconcentration: 0.73.
      There were 10 deaths (mortality: 3%). There were no significant differences
      between BISAP and APACHE-II, urea or hemoconcentration, but a significant
      difference existed with Ranson score. CONCLUSION: BISAP is a simple score that
      applied early in the emergency room identifies patients with severe pancreatitis
      with an efficacy similar to APACHE-II, urea and hemoconcentration, and KEY WORDS:
      acute pancreatitis, BISAP, severity, prognostic scoring.

PMID- 23128944
TI  - [Bisap-O: obesity included in score BISAP to improve prediction of severity in
      acute pancreatitis].
AB  - INTRODUCTION: Most patients with acute pancreatitis exhibits a self-limiting
      clinical course and relatively free of major complications. Several scores have
      been created with the intention of achieving adequate and early predict the
      severity of pancreatitis in order to reduce this mortality. BISAP score was
      validated in 2008 as a predictor of mortality for acute pancreatitis, obesity is
      an independent risk factor that increases the risk of severity in patients with
      acute pancreatitis.The aim of this study is to determine whether obesity BISAP
      added a score improves prediction of severity in patients with acute
      pancreatitis. MATERIAL AND METHODS: This study was conducted in Daniel Alcides
      Carrion Hospital, Lima, Peru. The patient data were collected in the Emergency
      Service, it was a cross-sectional retrospective study, between January 2009 and
      June 2010. RESULTS: We evaluated a total of 99 patients with acute pancreatitis.
      Etiology of the 99 were biliary pancreatitis. Only 2 ended in death (2%). Most
      cases occurred in female patients 77/22 (77.8%). Sixteen of the 99 patients (16%)
      were considered severe acute pancreatitis. 90% (89/99) had a BISAP <3, 10% a
      BISAP >= 3, fifteen of the 99 patients had a BISAP-O> 3, of them 12 were actually
      considered a severe pancreatitis. Of 16 patients with severe pancreatitis, 14
      patients had a BMI>25. (P = 0.03, OR = 4.39). BISAP-O has a sensitivity,
      specificity, PPV and NPV of 75%, 96.4%, 80% and 95.2% respectively, with an
      accuracy of 92.3%. The area under the curve for BISAP-O was 0.94 (95% CI 0.89 to
      0.99). There was no difference when compared with the other studied scores (p =
      0.45). CONCLUSIONS: BISAP The score is a simple method that can be used to
      predict the severity of acute pancreatitis. Obesity associated BISAP (BISAP-O)
      provides higher sensitivity and diagnostic accuracy to score BISAP and can serve
      as a parameter to help predict severity in patients with acute pancreatitis. It
      was not possible to assess the BISAP-O score as a predictor of mortality for
      patients with acute pancreatitis, due to the low mortality rate in the present
      study. Further studies are required to validate the score BISAP associated with
      obesity in predicting severity.

PMID- 23128945
TI  - [Evaluation and validation of surgical indications in acute pancreatitis with
      necrosis, at the National Hospital Edgardo Rebagliati Martins].
AB  - OBJECTIVE: The purpose of this study is to evaluate efficacy of the surgical
      indications in acute pancreatitis. MATERIAL AND METHODS: During the period from
      May 2000 to June 2009, 107 operated patients with pancreatic necrosis were
      treated in the Severe Acute Pancreatitis Unit of the HNERM a comparison was made
      by separating the patients in two groups according to the surgical indication. An
      analysis was carried out in order to evaluate which type of surgical indication
      has the best results according to age, severity of the case, return to oral
      intake, hospital stay, complications and mortality. RESULTS: On evaluating the
      indication by positive puncture for detecting necrosis infection we found that
      89% of the patients operated due to this indication showed infected necrosis
      while those operated due to the indication of "sepsis without response to the ICU
      treatment" only reached 51%. Surgical complications and re operations, was higher
      among the patients whose indication was "sepsis without response to the ICU
      treatment" (Indication B) in comparison with positive FNA. (Indication A)
      CONCLUSION: Positive fine needle aspiration is the surgical indication par
      excellence in acute pancreatitis with necrosis. We consider that the indication
      of "sepsis that do not respond for more than 72 hours to treatment in the ICU
      regardless that negative FNA" should not be taken into account, due to the very
      high percentage of sterile necrosis found at the time of surgery.

PMID- 23128946
TI  - [Glycemic dysfunction prevalence post acute pancreatitis. A prospective study].
AB  - OBJECTIVE: To estimate the prevalence of altered metabolism of carbohydrates in
      patients with mild acute pancreatitis. METHODS: We included 85 patients diagnosed
      with pancreatitis. We used to evaluate prognosis Balthazar and Ranson criteria.
      All patients were interviewed and examined. Was performed routine laboratory and
      Oral glucose tolerance test (OGTT) We excluded patients with previous diagnosis
      of diabetes mellitus, alcoholic pancreatitis, severe hypertriglyceridemia and
      recurrent/ severe pancreatitis. RESULTS: 30 women and 27 men. After performing
      the OGTT were classified into three groups. Group 1 (n: 19): normal OGTT; Group 2
      (n: 33): GAA, IHC, or both, and Group 3 (n = 5): with diabetes mellitus. Patients
      in group 3 had a higher average age (p = 0.02), and higher diastolic blood
      pressure (DBP) (p = 0.048). We observe a significant difference in fasting
      glucose values (p = 0.0001) and 120 minutes post-OGTT in all groups (p = 0.0001).
      HOMA was found higher (p = 0.031) in group 2. CONCLUSIONS: This study showing a
      link between mild acute pancreatitis and dysfunction of glucose metabolism, which
      found older patients, DBP and those with metabolic syndrome, had a higher
      prevalence of 65.66% of Pre diabetes and diabetes.

PMID- 23128947
TI  - [Appendiceal inflammatory mass management in adult patients at Cayetano Heredia
      National Hospital].
AB  - OBJECTIVE: To know the outcomes of the management of adult patients with
      appendiceal inflammatory mass at Cayetano Heredia National Hospital. MATERIAL AND
      METHODS: This is a retrospective and descriptive study, where data collection
      from medical records of patients with appendiceal inflammatory mass who were
      managed at Cayetano Heredia National Hospital from 2006 to 2010 was done.
      RESULTS: 77 patients were included in this study. 41 (53.25%) were male and mean
      age was 35 years. The incidence of appendiceal inflammatory mass was 2.76%. Mean
      time of symptoms was 8 days. Conservative treatment succeeded in 88.31% of
      patients, interval appendicectomy was performed in 11.76%, mean time till
      interval surgery was 3.5 months. Nine patients (11.69%) did not respond to
      conservative management and underwent emergency surgery. Mortality was 0%.
      CONCLUSIONS: In Cayetano Heredia National Hospital, the incidence of appendiceal
      inflammatory mass is 2.76%. 88.31% of patients respond to conservative treatment,
      of which interval appendicectomy is performed in 11.76%.

PMID- 23128948
TI  - [Nutritional status morbility and mortality in patients with gastrointestinal
      anastomosis in the "Hospital Nacional Hipolito Unanue" (HNHU)].
AB  - OBJECTIVES: [corrected] To estimate the nutritional status of patients undergoing
      gastrointestinal anastomoses. To determine which test used for the malnutrition
      diagnose is better correlated with the presence of complications. METHODS: The
      nutritional status of 136 patients was done with hematologic and anthropometric
      tests and Subjective Global Assessment (SGA). The morbidity and mortality were
      recorded to identify the difference between well-nourished and malnourished
      patients. RESULTS: 85 (62,5%) patients were males. Malnutrition rate according to
      albumin, lymphocyte count, BMI, UAC (upper arm circumference) and SGA was 54,5%;
      58,9%; 19,1%; 50,7% y 44,9% respectively. 44 (32,4%) patients had complications.
      It was found a statistically significant relationship for albumin and SGA for
      complications when comparing with the multiple regression analysis. The length of
      stay average was 10,7 days for well-nourished patients and 25,22 days for
      malnourished patients (p<0,005). The mortality rate was 7,5%. CONCLUSIONS: The
      prevalence of malnutrition in surgical patients is high. Malnutrition is
      associated with complications and increased length of stay. The albumin and SGA
      are good parameters to value the nutrition status and the correlation with
      complications.

PMID- 23128949
TI  - [Utility of the capilar pattern in the NBI diagnosis of superficial lesions of
      the colon: prospective validation in a private endoscopic center Lima, Peru].
AB  - INTRODUCTION: It is important to detect and remove adenomas in order to prevent
      colon cancer. Angiogenesis is an early change in the pre malignant transformation
      sequence and narrow band imaging (NBI) allows for better visualization of the
      capillary pattern of the mucosa. OBJECTIVE: We present our data regarding the
      assessment of superficial lesions of the colon on colonoscopies using NBI as well
      as the Sano-Emura classification. MATERIALS & METHODS: Prospective study done in
      Lima Peru. Three endoscopists evaluate the capillary pattern of colonic lesions
      in real time using NBI and electronic magnification. These findings are then
      compared to the pathology report. RESULTS: 380 patients were evaluated with a
      total of 739 lesions; 473 adenomas, 241 non neoplastic lesions, and 25 serrated
      lesions. These were grouped depending on their NBI capillary pattern into two
      groups: Neoplastic (Sano-Emura types II, IIIa, and IIIb), and Non-Neoplastic
      (Sano-Emura type I). Sensitivity for adenomas 84%, diagnostic accuracy 77%, PPV
      82%, NPV 67%, specificity 63%. Sensitivity and diagnostic accuracy improved to
      94% and 84%, respectively when evaluating lesions of 5 mm to 9 mm. For diminutive
      rectosigmoid polyps, the NPV for adenomas was 81%. The serrated lesions showed
      both types of capillary pattern with equal frequency. CONCLUSIONS: Our results
      using NBI with electronic magnification showed that this method is useful for the
      differentiation of lesions 5 mm or bigger, as reported previously. Accuracy was
      diminished when evaluating lesions less than 5 mm. NBI was not capable of aiding
      in the differential diagnosis of serrated lesions.

PMID- 23128950
TI  - [Clinical and therapeutic issues in children and adolescents with liver
      hidatidosis at the Hipolito Unanue National Hospital].
AB  - The aim of this study is to evaluate the clinical diagnosis and treatment of
      pediatrics patients with hepatic hydatid disease hospitalized in the pediatric
      ward of HNHU in the last ten years. The study is a descriptive, cross-sectional
      and retrospective observational of patients undergoing surgery for liver
      hydatidosis. We studied 42 confirmed cases of hepatic hydatidosis, the ages
      ranged from 1 to 17 years and most were adolescents 13 to 17 years (20 cases
      47.62%), the gender distribution is equal and the source of patients is mainly
      from the Central Andes of Peru (24 cases 57.14%) followed by Lima city (10 cases
      23.81%). The most common presenting symptom was abdaominal pain (29 cases 69.05%)
      followed by fever (19 cases 45.24%). Ultrasound is the most common diagnostic
      method and only not done in a patient carrying a prior CT scan. Serology
      (indirect immunofluorescence) was positive in only 19 of 27 patients who had the
      test (70%).Most were single hepatic cysts (22 cases 52.38%) with size from 3 to
      20 cm but most commonly they were 5 to 10 cm sized. The location was predominant
      on the right lobe (26 cases 61.98%) followed on both lobes (10 cases 23.81%).
      Apart from the liver there were cysts on the lungs (18 cases 42.86%).The surgical
      procedure performed was radical cystectomy with or without drainage in 36 cases
      (85.71%). And conservative surgery in only 6 cases (14.28). The important
      complications were: 15 cases of fever (35.71), nosocomial respiratory infection
      in 9 cases (21.43%), biliary fistula in 5 cases (11.90%) and residual abscess in
      3 cases (7.14%). Although morbidity was high, mortality of the cases studied was
      zero.

PMID- 23128951
TI  - [Therapy for early gastric cancer with submucosal endoscopic disection using the
      IT-Knife 2].
AB  - 70 years old woman, without history of illness, came to the Digestive Endoscopic
      Center of the Gastroenterology department of Arzobispo Loayza hospital, with the
      diagnosis of Abdominal pain syndrome, in which Upper Endoscopy was practiced.
      Upper endoscopy concludes the diagnosis of a malignant lesion probably an Early
      gastric cancer type IIa+IIc, which was confirmed with pathology. Endoscopic
      treatment was done with Endoscopic submucosal dissection (ESD). The lesion was
      totally removed, in accordance with the pathologist. Endoscopic controls at 10
      weeks showed retractable red scar and a negative biopsy for neoplasm. This case
      is reported for being the first one published in our literature in which
      therapeutic ESD with IT-Knife2, was done in Early Gastric cancer.

PMID- 23128952
TI  - [Primary melanoma of the esophagus].
AB  - Primary malignant melanoma of the esophagus is a rare, aggressive and poor
      prognostic neoplasm, usually detected in late stages. Surgery (esophagectomy) is
      the treatment of choice when operable and the only factor that improves the
      disease prognosis is the detection of the lesions in early stages and the
      recognition of non-typical lesions. Most commonly, Melanoma lesions appear as
      large masses with proliferative, ulcerated and pigmented aspect. We report a
      clinical case whose endoscopic presentation was an elevated, protruding and
      sessile lesion (Paris Classification Type 0- Is), amelanocytic, size of 4mm,
      smooth surface, pink and with regular borders (mucosa of tumor with a normal
      esophagic mucosa appearance). This lesion initially could not be identified
      because the patient was admitted due to upper gastrointestinal bleeding caused by
      peptic esophagitis Grade D according to Los Angeles Classification. After
      histological analysis and immunohistochemistry of the lesion, melanoma was
      diagnosed. No skin, mucous or ocular lesions were found and multislice spiral
      computed tomography of thorax and abdomen did not show any metastasis.

PMID- 23128953
TI  - [EUS-guided access to dorsal pancreatic duct in a patient with pancreas divisum].
AB  - Case report of pancreas divisum dorsal pancreatic duct access with endoscopic
      ultrasonography help to relief pain in a patient with not possible access by
      PCRE.

PMID- 23128954
TI  - [Pancreatico-jejunostomy in defunctionalized Roux-Y loop. An alternative for low
      volume hospitals].
AB  - This case is about a one obesity patient to carry out pancreaticoduodenectomy for
      solido pseudopapilary cyst of the pancreatic head, considerate in pancreatic
      surgery like high risk for to present soft pancreatic, wirsung smaller to 2mm and
      not bile duct dilatation .The pancreaticojejunostomy was performed end to end
      with invagination of the pancreatic stump with suture in tobacco bag to a
      defunctionalized jejunal loop Y the Roux to avoid middle alkali of the bile duct 
      jejunostomy.

PMID- 23128955
TI  - [Hepatic angiosarcoma: case report and review of literature].
AB  - Hepatic Angiosarcoma is an uncommon neoplasia with an incidence between 0.5 to 2
      % of primary hepatic tumors. Due to a nonspecific presentation it is very
      difficult to reach the diagnosis which is usually late and by that time the organ
      has been involved by tumor and surgical treatment is not possible. Because of CT
      limitations for staging and metastasis diagnosis, laparoscopy is used because it
      gives us better vision of the abdominal cavity and reliable information about
      tumor staging and prognosis. Final diagnosis is pathological and require
      inmunohistochemical confirmation with CD-31 and CD-34. Chemotherapy and
      radiotherapy have not demonstrated an improvement in the survival rate which is 6
      months without treatment since diagnosis.We present a case of a 41 yo male
      patient without significant history with 2 months of nonspecific symptoms related
      to an hepatic tumor and ascites.

PMID- 23128956
TI  - Impact of respiration on electroanatomical mapping of the right atrium:
      implication for cavotricuspid isthmus ablation.
AB  - PURPOSE: Cavotricuspid isthmus (CTI) ablation for typical atrial flutter (AFL)
      has become the preferred treatment for this arrhythmia. The aims of this study
      were to assess the impact of respiratory gating (RG) on electroanatomical mapping
      of CTI and to assess the efficiency of CTI ablation guided by the Carto3(r)
      system equipped with the new respiration gating software. METHODS: Forty-four
      consecutive patients (mean age, 60 +/- 13 years; 25 male) undergoing
      cavotricuspid ablation for symptomatic common AFL were randomly assigned to
      CARTOTM mapping with or without enabling RG module (Group A, RG OFF, Group B, RG
      ON). RESULTS: A significant reduction in mean RA volume, CTI central length and
      CS ostium maximum diameter has been observed in the RG maps. The mean total
      procedural, fluoroscopy and radiofrequency (RF) time were 102.9 +/- 35.3, 10.6 +/
      3.3, 22.9 +/- 14.2 min in group A and 75.3 +/- 21.7, 3.6 +/- 4.5, 10.4 +/- 5.7
      min in group B, respectively (p < 0.05). CONCLUSIONS: Electroanatomical mapping
      systems' accuracy may be strongly influenced by respiration movements. The
      current study showed that automatic respiratory gated acquisition resulted in a
      better visualization of CTI, and this determines a relevant reduction in
      fluoroscopy and RF times.

PMID- 23128957
TI  - Potential of mesenchymal stem cell applications in plastic and reconstructive
      surgery.
AB  - : Novel therapy with mesenchymal stem cells from bone marrow, adipose tissue, or
      other sources has raised high hopes for treatment of a variety of diseases. For
      plastic and reconstructive surgery, first pilot studies and clinical trials using
      stem cells for treatment of chronic wounds, radiation injury, or soft tissue
      augmentation have furnished encouraging results compared with the limitations of
      standard therapy, for example autologous fat grafting. Further research must be
      conducted to reveal the complex physiological interactions between activated stem
      cells and the host environment. Long-term effects and safety aspects of these
      novel treatment options also require randomized controlled studies. For future
      clinical applications, guidelines and standardized procedures for stem cell
      isolation and preparation, and techniques for application must be established. 

PMID- 23128958
TI  - Macrophages overexpressing Aire induce CD4+Foxp3+ T cells.
AB  - Aire plays an important role in central immune tolerance by regulating the
      transcription of thousands of genes. However, the role of Aire in the peripheral
      immune system is poorly understood. Regulatory T (Treg) cells are considered
      essential for the maintenance of peripheral tolerance, but the effect of Aire on
      Treg cells in the peripheral immune system is currently unknown. In this study,
      we investigated the effects of macrophages overexpressing Aire on CD4+Foxp3+ Treg
      cells by co-culturing Aire-overexpressing RAW264.7 cells or their supernatant
      with splenocytes. The results show that macrophages overexpressing Aire enhanced
      the expression of Foxp3 mRNA and induced different subsets of Treg cells in
      splenocytes through cell-cell contact or a co-culture supernatants. TGF-beta is a
      key molecule in the increases of CD4+CD45RA+Foxp3hi T cell and activating Treg
      (aTreg) levels observed following cell-supernatant co-culturing. Subsets of Treg
      cells were induced by Aire-overexpressing macrophages, and the manipulation of
      Treg cells by the targeting of Aire may provide a method for the treatment of
      inflammatory or autoimmune diseases. 

PMID- 23128959
TI  - Optimizing the use of oral anti-neoplastic drug therapy.

PMID- 23128960
TI  - Retinal pigment epithelium, age-related macular degeneration and neurotrophic
      keratouveitis.
AB  - Age-related macular degeneration (AMD) is the leading cause of impaired vision
      and blindness in the aging population. The aims of our studies were to identify
      qualitative and quantitative alterations in mitochondria in human retinal pigment
      epithelium (RPE) from AMD patients and controls and to test the protective
      effects of pigment epithelium-derived factor (PEDF), a known neurotrophic and
      antiangiogenic substance, against neurotrophic keratouveitis. Histopathological
      alterations were studied by means of morphometry, light and electron microscopy.
      Unexpectedly, morphometric data showed that the RPE alterations noted in AMD may
      also develop in normal aging, 10-15 years later than appearing in AMD patients.
      Reduced tear secretion, corneal ulceration and leukocytic infiltration were found
      in capsaicin (CAP)-treated rats, but this effect was significantly attenuated by
      PEDF. These findings suggest that PEDF accelerated the recovery of tear secretion
      and also prevented neurotrophic keratouveitis and vitreoretinal inflammation.
      PEDF may have a clinical application in inflammatory and neovascular diseases of
      the eye.

PMID- 23128961
TI  - 5-year morbidity among very preterm infants in relation to level of hospital
      care.
AB  - OBJECTIVE: To determine whether birth and care in the highest-level hospitals
      (level III) compared with birth in or postnatal transfer to lower-level hospitals
      (level II) are associated with 5-year morbidity in very preterm children. DESIGN:
      A cohort study. SETTING: Finland. PARTICIPANTS: All surviving 5-year-old children
      born very preterm (gestational age <32 weeks or birth weight <=1500 g) born in
      level II or level III hospitals (n = 2168) and full-term (gestational age, 37-42
      weeks) children (n = 238 857) born from January 1, 2000, through December 31,
      2004. MAIN OUTCOME MEASURES: Diagnoses issued after the first discharge home and
      overrepresented in very preterm compared with full-term children. Diagnoses were
      analyzed between very preterm children (1) born and treated in level III
      hospitals (group III), (2) born in level III and transferred to lower-level
      hospitals (group III/II), and (3) born and treated in level II hospitals (group
      II). RESULTS: Group III/II children had an increased incidence of retinal
      disorders (odds ratio, 2.43 [95% CI, 1.66-3.56]) and asthma (1.41 [1.09-1.81])
      but fewer viral infections (0.75 [0.59-0.95]) compared with group III infants.
      The risks for epilepsy (odds ratio, 2.71 [95% CI, 1.29-5.70]) and hyperkinetic
      disorders (2.19 [1.13-4.25]) were higher among group II than among group III
      children. No statistically significant differences between the groups for the 14
      other diagnoses were found. CONCLUSIONS: The increased incidence of retinopathy
      and asthma among infants transferred from level III to lower-level hospitals
      calls for analysis of the differences in treatment practices between hospital
      levels.

PMID- 23128962
TI  - Synthesis, properties and applications of colloidal germanium and germanium-based
      nanomaterials.
AB  - Germanium nanoparticles have excited scientists and engineers because of their
      size-dependent optical properties and their potential applications in
      optoelectronics, biological imaging and therapeutics, flash memories, and lithium
      ion batteries. In order to further develop these applications and to gain deeper
      insights into their size-dependent properties, robust and facile synthetic
      methods are needed to controllably synthesize Ge nanoparticles. However, when
      compared to other II-VI, IV-VI, and III-V semiconductor systems, colloidal routes
      to Ge NPs with uniform sizes and shapes are much less mature. In this Review
      Article, we highlight the progress that has been made in this field and provide
      insights into the strategies used for the colloidal synthesis of size and shape
      controlled germanium nanomaterials. We also survey some of the potential
      applications of these materials in optoelectronics, biological imaging, and
      energy conversion and storage. Finally, we discuss the colloidal synthesis of
      other germanium-containing compounds, emphasizing technologically relevant
      germanium chalcogenides that include GeS, GeSe, and GeTe.

PMID- 23128963
TI  - Serum ibuprofen levels of extremely preterm infants treated prophylactically with
      oral ibuprofen to prevent patent ductus arteriosus.
AB  - AIM: The aim of this study was to explore the effects of early oral ibuprofen
      administration on the incidence of hemodynamically significant patent ductus
      arteriosus (hsPDA) and define the association between serum ibuprofen levels and
      ductal closure. METHOD: Preterm infants with a gestational age of <28 weeks
      and/or birth weight of <1,000 g were randomized either to the intervention
      (ibuprofen prophylaxis) or control group. The intervention group received oral
      ibuprofen 10 mg/kg within 12-24 h after birth followed by 5 mg/kg at 24 and 48 h.
      Serum ibuprofen levels after the treatment were analyzed in the intervention
      group, and the incidence of hsPDA and complication rates were compared between
      two groups. RESULTS: Nineteen infants who received one course (three doses) of
      prophylactic ibuprofen in the intervention group and 17 infants in the control
      group who underwent an echocardiographic examination on the fourth day of life
      were analyzed. hsPDA was observed in five (26 %) infants in the intervention
      group and ten (58 %) infants in the control group (p = 0.09). In the intervention
      group two infants experienced gastrointestinal bleeding two infants had
      spontaneous intestinal perforation, and two infants developed acute kidney
      failure. Mean serum ibuprofen level was 28.7 +/- 16.9 mg/L in the intervention
      group, and there was no correlation between ibuprofen level obtained on the
      fourth day and ductal closure. CONCLUSION: Oral ibuprofen prophylaxis reduces the
      rates of hsPDA even it is not statistically significant. The ductal closure rate
      did not correlate with serum ibuprofen levels. Due to high prevalence of adverse
      events observed, our data do not support the use of oral ibuprofen for
      prophylaxis of hsPDA.

PMID- 23128964
TI  - The reproducibility of bolus allergen challenges; power calculations for clinical
      trials.

PMID- 23128965
TI  - Danish physicians' preferences for prescribing escitalopram over citalopram and
      sertraline to treatment-naive patients: a national, register-based study.
AB  - PURPOSE: To investigate whether general practitioners, hospital physicians and
      specialized practitioners in psychiatry have similar preferences for initiating
      treatment with expensive serotonin-specific reuptake inhibitors (SSRIs). METHODS:
      All first-time prescriptions for the SSRIs escitalopram, citalopram and
      sertraline reported to the Danish National Register of Medicinal Product
      Statistics from April 1, 2009 until March 31, 2010 were analysed with regard to
      treatment naivety and type of prescriber. A prescription was considered as first
      time if the patient had not received a prescription for the same drug within the
      last 2 years. Patients who had not received a prescription for an antidepressant
      within 6 months prior to the date of redemption were classified as treatment
      naive. RESULTS: We included 82,702 first-time prescriptions, 65,313 (79 %) of
      which were for treatment-naive patients. Of the treatment-naive patients, 19 %
      were initially prescribed escitalopram. Hospital physicians prescribed
      escitalopram to 34 % of their treatment-naive patients, while practitioners
      specialized in psychiatry prescribed it to 25 %, and general practitioners
      prescribed it to 17 %. General practitioners, however, were responsible for
      initiating 87 % of all treatment-naive patients. CONCLUSION: The most expensive
      SSRI, escitalopram, is prescribed as first choice to one in five patients
      receiving their first antidepressant of escitalopram, citalopram or sertraline.
      General practitioners made the bulk of all first-time SSRI prescriptions to
      treatment-naive patients.

PMID- 23128966
TI  - Silicon nanowires as a rechargeable template for hydride transfer in redox
      biocatalysis.
AB  - We report a new possible application of hydrogen-terminated silicon nanowires (H
      SiNWs) as a rechargeable template for hydride transfer in redox biocatalysis. H
      SiNWs transfer hydride efficiently to regenerate NADH by oxidizing Si-H(x) bonds.
      The oxidized H-SiNWs were readily recharged for the continuous regeneration of
      NADH and enzymatic reactions.

PMID- 23128967
TI  - Enantioselective transfer hydrogenation of ketone catalysed by artificial
      metalloenzymes derived from bovine beta-lactoglobulin.
AB  - Artificial metalloproteins resulting from the embedding of half-sandwich
      Ru(II)/Rh(III) fatty acid derivatives within beta-lactoglobulin catalysed the
      asymmetric transfer hydrogenation of trifluoroacetophenone with modest to good
      conversions and fair ee's.

PMID- 23128968
TI  - Effect of cilostazol in acute lacunar infarction based on pulsatility index of
      transcranial Doppler (ECLIPse): a multicenter, randomized, double-blind, placebo
      controlled trial.
AB  - BACKGROUND: This study is intended to evaluate the propensities of cilostazol to
      reduce the pulsatility index (PI) in patients with acute lacunar infarction using
      the serial transcranial Doppler (TCD) examinations. METHODS: In a multicenter,
      randomized, double-blind, placebo-controlled trial, patients were randomly
      assigned to receive either placebo or 100 mg cilostazol twice a day as well as
      aspirin 100 mg a day. The primary outcomes were the changes of middle cerebral
      artery (MCA) and basilar artery (BA) PIs at 14 and 90 days from the baseline TCD
      study. This study is registered with ClinicalTrials.gov (NCT00741286). RESULTS:
      Trial medication was given to 203 patients, with 100 receiving cilostazol and 103
      receiving placebo, and 164 were included in the per-protocol analysis of the
      primary outcome. Results from the linear mixed model showed that significant
      effects were obtained for time-by-group interactions (p = 0.008 in right MCA, p =
      0.015 in left MCA, p = 0.002 in BA), suggesting that changes of PIs from the
      baseline to the 90-day study were different across the groups. CONCLUSIONS:
      Cilostazol further decreased TCD PIs at 90 days from baseline compared to placebo
      in acute lacunar infarction. This result may be related to pleiotropic effects,
      such as vasodilation, beyond its antiplatelet activity.

PMID- 23128969
TI  - White matter hyperintensity volume and impaired mobility among older adults.
AB  - Gait speed is associated with multiple adverse outcomes of aging. White matter
      hyperintensities (WMH) on magnetic resonance imaging (MRI) have been associated
      with gait speed, though few studies have examined changes in gait speed over time
      in population-based studies comprising participants from diverse cultural
      backgrounds. The purpose of this study was to examine the association between a
      decline in gait speed and total and regional WMH volumes in a community-based
      study of aging. Participants (n = 701) underwent gait-speed measurement via a 4-m
      walk test at the time of initial enrollment and MRI at a second time interval
      (mean 4.7 [SD = 0.5] years apart). Logistic regression was used to examine the
      association between large WMH volume and regional WMH volume with gait speed <0.5
      m/s (abnormal speed), and a transition to abnormal gait speed. Analyses were
      adjusted for demographic and clinical factors. Large WMH volume was associated
      with abnormal gait speed and a transition to abnormal gait speed between the two
      visits, but not after adjustment for modifiable vascular disease risk factors.
      Increased frontal lobe WMH volume was associated with abnormal gait speed and
      transition to abnormal gait speed, but not in adjusted models. WMH are associated
      with slowing of gait over time. Prevention of WMH presents a potential strategy
      for the prevention of gait speed decline.

PMID- 23128970
TI  - Global functional connectivity reveals highly significant differences between the
      vegetative and the minimally conscious state.
AB  - A major challenge in the diagnosis of disorders of consciousness is the
      differential diagnosis between the vegetative state (VS) and the minimally
      conscious state (MCS). Clinically, VS is defined by complete unawareness, whereas
      MCS is defined by the presence of inconsistent but clearly discernible
      behavioural signs of consciousness. In healthy individuals, pain cries have been
      reported to elicit functional activation within the pain matrix of the brain,
      which may be interpreted as empathic reaction. In this study, pain cries were
      presented to six VS patients, six MCS patients, and 17 age-matched healthy
      controls. Conventional task-related functional magnetic resonance imaging (fMRI)
      showed no significant differences in functional activation between the VS and MCS
      groups. In contrast to this negative finding, the application of a novel data
      driven technique for the analysis of the brain's global functional connectivity
      yielded a positive result. The weighted global connectivity (WGC) was
      significantly greater in the MCS group compared to the VS group (p < 0.05, family
      wise error corrected). Using areas of significant WGC differences as 'seed
      regions' in a secondary connectivity analysis revealed extended functional
      networks in both MCS and healthy groups, whereas no such long-range functional
      connections were observed in the VS group. These results demonstrate the
      potential of functional connectivity MRI (fcMRI) as a clinical tool for
      differential diagnosis in disorders of consciousness.

PMID- 23128972
TI  - Diagnosis of chronic mesenteric ischemia in older patients: a structured review.
AB  - BACKGROUND AND AIMS: Chronic mesenteric ischemia in older patients is a challenge
      for the physician because it coincides with a vague and non-specific clinical
      presentation with abdominal pain. It can frequently cause diagnostic errors and
      lead to legal consequences. The aim of this work was to evaluate the literature
      on chronic mesenteric ischemia and focus on the limited data concerning the
      geriatric population. METHODS: This research focused on observational studies,
      randomized controlled trials, and clinical reports (excluding case reports and
      reviews) dealing with patients at least 65 years old with a clinical or
      instrumental diagnosis of chronic intestinal ischemia, published between 2000 and
      2010. The search was conducted in PubMed using the following key words: chronic
      ischemic splanchnic disease, chronic mesenteric ischemia, angina abdominis,
      chronic abdominal angina, intestinal ischemia. RESULTS: We selected 925 articles
      with the key words as follows: chronic mesenteric ischemia in 355 cases; chronic
      ischemic splanchnic disease in 46; angina abdominis in 4; abdominal angina in
      242; and chronic intestinal ischemia in 278. We then excluded articles judged
      scarcely pertinent, case reports, reviews, works concentrating only on
      diagnostic, methodological, instrumental and surgical approaches, and articles
      based on animal or experimental models. This selection left us with 13 articles
      (after excluding duplicates), only three of which were considered valid for our
      purposes. CONCLUSIONS: Our review indicates that there is a shortage of useful
      literature on chronic intestinal ischemic disease diagnosed in the older adults,
      and the appropriate geriatric management of these patients is consequently not
      well established.

PMID- 23128971
TI  - Optical microangiography provides correlation between microstructure and
      microvasculature of optic nerve head in human subjects.
AB  - It is demonstrated that optical microangiography (OMAG) is capable of imaging the
      detailed microstructure and microvasculature of the in vivo human optic nerve
      head (ONH), including the prelaminar tissue, the lamina cribrosa, the scleral rim
      and the vessels in the region of the circle of Zin-Haller. For demonstration, an
      ultrahigh sensitive OMAG system operating in the 850 nm wavelength region and a
      500 kHz A-scan rate resulting in a spatial resolution of ~6  MUm were used. It
      was shown that OMAG provides superior results for three-dimensional imaging of
      the ONH compared to conventional optical coherence tomography by simultaneously
      recording both the microstructure and the functional microcirculation. The blood
      supply to the tissues of the ONH is an essential physiologic parameter needed for
      clinical assessment of the health of the nerve.

PMID- 23128973
TI  - Tacrolimus-associated ischemic optic neuropathy and posterior reversible
      encephalopathy syndrome after small bowel transplantation.

PMID- 23128974
TI  - Living-donor liver transplantation from donor with a left-sided gallbladder with
      portal vein anomaly.

PMID- 23128975
TI  - Hypersensitivity reaction to intravenous but not oral tacrolimus.

PMID- 23128976
TI  - Extrahepatic bile duct measurement by using transabdominal ultrasound in Japanese
      adults: multi-center prospective study.
AB  - BACKGROUND: In adults, less than 10-mm bile duct has idiomatically been
      recognized as "non-dilated bile duct" though there was no obvious evidence. The
      aim of this study was to prospectively examine the maximum inner diameter of
      extrahepatic bile duct (MDEBD) in consecutive adults. METHODS: Transabdominal
      ultrasound (US) was performed to measure the MDEBD of 8840 cases (4420 male) in
      five institutions. The frequency of ultrasound probe ranged from 3.5 to 5 MHz.
      RESULTS: The mean diameter of MDEBD was 4.5 +/- 1.4 mm (range 1-14 mm). The
      relationship between the MDEBD and age was shown as follows: MDEBD = 2.83 + 0.03
      * age. Multiple regression analysis was analyzed between 6 groups and significant
      alpha level is 0.008 in this analysis. In all age groups but 20s and 30s, there
      was statistically significant MDEBD among each age group (p < 0.0001). Mean, mode
      value and median MDEBD is increasing according to the age as follows: 20s: 3.9 +/
      1.0 mm, 30s: 3.9 +/- 1.2 mm, 40s: 4.3 +/- 1.2 mm, 50s: 4.6 +/- 1.3 mm, 60s: 4.9
      +/- 1.4 mm, >70s: 5.3 +/- 1.6 mm. CONCLUSION: The present study revealed that
      MDEBD positively correlates with age. Therefore, when we examine the presence of
      dilation of the bile duct, our calculating formula appears to be suitable for
      accurate evaluation.

PMID- 23128977
TI  - Human papillomavirus 16/18 E5 promotes cervical cancer cell proliferation,
      migration and invasion in vitro and accelerates tumor growth in vivo.
AB  - High-risk human papillomaviruses (HR-HPVs) are consistently associated with human
      cervical cancer Additionally, the early oncoproteins of HPVs E5, E6 and E7 are
      known to contribute to tumor progression. The role of E5 is still nebulous. In
      this study, we aimed to explore the mechanism of E5 action during the human
      cervical carcinogenesis process. We created four cell models overexpressing HPV16
      or HPV18 E5 (HPV16/18 E5) and investigated their ability to proliferate, along
      with their metastatic characteristics such as migration and invasion. The
      expression of HPV16/18 E5 protein in various cell lines was analyzed by reverse
      transcriptase-polymerase chain reaction (RT-PCR). In addition, we compared the
      levels of phosphorylated paxillin as well as E-cadherin in cell models and
      controls by western blot analysis. Finally, we assessed the tumor growth rate of
      human cervical cancer cells overexpressing HPV16/18 E5 in vivo. We discovered
      that the expression of HPV16/18 E5 consistently increased the malignant potential
      of various human cervical cancer cells compared with the primary counterparts. We
      demonstrated the involvement of HPV16/18 E5 in proliferation, migration, invasion
      and regulation of the actin cytoskeleton in human cervical cancer cells. In
      particular we discovered that HPV16/18 E5 overexpression in human cervical cancer
      cells correlated with higher levels of paxillin proteins phosphorylated on
      tyrosine residues and with the downregulation of E-cadherin. Importantly,
      injection of HPV16/18 E5-overexpressing human cervical cancer cells into mice
      increased both HPV-and non-HPV-derived tumor growth. Collectively, our data
      indicate that HPV16/18 E5 influences progression of the human cervical cancer
      malignant phenotype. This study provides new insights into HPV16/18 E5 as a
      possible agent that may have an impact on the therapeutic strategies targeting
      human cervical cancer.

PMID- 23128978
TI  - A systematic review to quantitatively evaluate 'Stepping Stones': a participatory
      community-based HIV/AIDS prevention intervention.
AB  - This first independent systematic review examined evidence for the effectiveness
      of the stepping stones intervention in HIV prevention. To reduce HIV transmission
      it addresses gender roles and promotes equitable relationships. Biomedical,
      behavioural and psychosocial outcomes extracted from six databases and 'grey'
      literature identified eight reports of seven studies (n = 14,630) from India,
      Gambia, S. Africa, Ethiopia, Angola, Tanzania, Uganda and Fiji. Infection
      incidence tested in the only RCT showed no significant reduction in HIV, although
      HSV-2 decreased. Condom use increased (two countries out of eight). Risk
      reduction results were mixed for declining alcohol misuse (two studies in three)
      and multiple partners (one in two). Communicating HIV information to partners,
      family or community improved (three studies from seven). Gender inequity was
      reduced in India (one in five), but stigma decreased in four studies. Future
      investigations of diverse cultures and older adults should select high quality
      biomedical and quality of life measures.

PMID- 23128979
TI  - Transitional care coordination in New York City jails: facilitating linkages to
      care for people with HIV returning home from Rikers Island.
AB  - New York City (NYC) jails are the epicenter of an epidemic that overwhelmingly
      affects Black and Hispanic men and offer a significant opportunity for public
      health intervention. The NYC Department of Health and Mental Hygiene instituted
      population based approaches to identify the HIV-infected, initiate discharge
      planning at jail admission, and facilitate post-release linkages to primary care.
      Using a caring and supportive 'warm transitions' approach, transitional care
      services are integral to continuity of care. Since 2010, over three-quarters of
      known HIV-infected inmates admitted to jails received discharge plans; 74 % of
      those released were linked to primary care. The EnhanceLink initiative's new
      Health Liaison, a lynchpin role, facilitated 250 court-led placements in medical
      alternatives to incarceration. Transitional care coordination programs are
      critical to facilitate continuity of care for people with chronic health
      conditions including the HIV-infected returning home from jail and for the public
      health of the communities to which they return.

PMID- 23128980
TI  - Perceived likelihood of using HIV pre-exposure prophylaxis medications among
      young men who have sex with men.
AB  - Pre-exposure prophylaxis (PrEP) is a new strategy for reducing the risk of HIV
      infection; however, questions about the likelihood of use remain. As part of an
      ongoing longitudinal study of YMSM, interest in PrEP use under various conditions
      of side-effects, dosing, and effectiveness were assessed. Participants aged 16-20
      living in Chicago and the surrounding areas were recruited beginning December
      2009, using a modified form of respondent driven sampling. A cross-sectional
      sample of 171 HIV negative YMSM interviewed approximately 6 months after initial
      enrollment was analyzed. This sample was somewhat interested in adopting PrEP as
      an HIV prevention strategy, particularly if the dosing and side-effects burden
      was low and the perceived benefits were high. PrEP interest was unrelated with
      drug use and number of sexual partners, but negatively correlated with number of
      unprotected anal sex acts. The scale was positively associated with intentions
      for use in specific risk situations.

PMID- 23128981
TI  - Hepatitis B virus X protein modulates remodelling of minichromosomes related to
      hepatitis B virus replication in HepG2 cells.
AB  - Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is organised into
      minichromosomes by histone and non-histone proteins. Remodelling of
      minichromosomes is crucial for the regulation of HBV replication, which is
      dependent on the presence of the hepatitis B virus X protein (HBx). However, the
      mechanisms of HBx-dependent HBV replication remain obscure. The objective of this
      study was to investigate the mechanism of HBx-dependent HBV replication through
      the pathway of chromatin remodelling. The role of HBx was investigated by
      transfecting human HepG2 cells with the linear full-length HBV genome (wild-type)
      or HBx-deficient mutant HBV DNA (HBx mutant). Our results showed that although
      the formation of cccDNA was not affected by HBx, HBV replication, transcription
      and antigen secretion were all significantly reduced, resulting from the absence
      of HBx. The acetylation, mono-methylation and phosphorylation of cccDNA-bound
      histone H3 were associated with HBV replication. In addition, the levels of
      cccDNA-bound methylated, phosphorylated and acetylated histone H3 decreased
      sharply in HBx mutant HBV DNA. HBx modulated not only the status of acetylation
      but also the methylation and phosphorylation of histone H3 bound to the cccDNA
      during HBV replication in HepG2 cells. These findings suggest that HBx plays an
      important role in modulating the remodelling of minichromosomes related to HBV
      replication and it may regulate viral replication through the pathway of
      chromatin remodelling.

PMID- 23128982
TI  - Anisotropic surface enhanced Raman scattering in nanoparticle and nanowire
      arrays.
AB  - Silver nanoparticles and nanowires self-aligned on pre-patterned rippled
      substrate are presented as active surface enhanced Raman scattering (SERS)
      substrates. The reported inter-particle gap of 5 nm and array periodicity of 35
      nm are much lower than current lithographic limits. The observed anisotropy in
      SERS and surface plasmon resonance in such arrays is attributed to different
      plasmonic field enhancement along and across the chains of nanoparticles not due
      to shape anisotropy. For nanoparticle arrays higher SERS intensity is found along
      the particle chain, but for nanowire arrays higher SERS intensity is found for
      excitation across the wires. Higher intensity across nanowire arrays supports the
      argument that the SERS phenomenon is due to electromagnetic field enhancement
      (hot-junctions) caused by localized surface plasmon resonance across the
      nanowires having a 35 nm gap. The effect of inter-particle gap, ordering, and
      aspect ratio on field enhancement is demonstrated. Higher SERS intensity is
      observed in aligned elongated nanoparticles compared to aligned spherical, non
      ordered nanoparticles, or aligned nanowires. Aligned silver nanowires enhance
      Raman scattering more strongly than aligned gold nanowires.

PMID- 23128983
TI  - Merging visible-light photoredox and Lewis acid catalysis for the
      functionalization and arylation of glycine derivatives and peptides.
AB  - A relay catalysis protocol for the functionalization of alpha-amino acids and
      dipeptides using a combination of visible-light photoredox and Lewis acid
      catalysis has been developed.

PMID- 23128984
TI  - A theoretical study of single-cell electroporation in a microchannel.
AB  - Electroporation of a single cell in a microchannel was studied. The effects of
      electrical (e.g., strength of the electric pulse) and geometrical (e.g.,
      microchannel height, electrode size and position) parameters on cell membrane
      permeabilization were investigated. The electrodes were assumed to be embedded in
      the walls of the microchannel; the cell was suspended between these two
      electrodes. By keeping the electric pulse constant, increasing the microchannel
      height reduces the number and the radius of the biggest nanopores, as well as the
      electroporated area of the cell membrane. If the width of the electrodes is
      bigger than the cell diameter, the transmembrane potential will be centralized
      and have a sinusoidal distribution around the cell if nanopores are not
      generated. As the width of the electrode decreases and becomes smaller than the
      cell diameter, the local transmembrane potential decreases; in the
      nonelectroporative area, the transmembrane potential distribution deviates from
      the sinusoidal behavior; the induced transmembrane potential also concentrates
      around the poles of the cell membrane (the nearest points of the cell membrane to
      the electrodes). During cell membrane permeabilization, the biggest nanopores are
      initially created at the poles and then the nanopore population expands toward
      the equator. The number of the created nanopores reaches its maximal value within
      a few microseconds; further presence of the electric pulse may not influence the
      number and location of the created nanopores anymore but will develop the
      generated nanopores. Strengthening the electric pulse intensifies the size and
      number of the created nanopores as well as the electroporated area on the cell
      membrane.

PMID- 23128985
TI  - Surface modification of polysulfone based hemodialysis membranes with layer by
      layer self assembly of polyethyleneimine/alginate-heparin: a simple
      polyelectrolyte blend approach for heparin immobilization.
AB  - This study intends to improve blood compatibility of polysulfone (PSF) membranes
      by generating a nonthrombogenic surface through heparin immobilization. To
      achieve this task, the support membrane prepared from a blend of PSF and
      sulfonated polysulfone (SPSF) was modified with layer by layer (LBL) deposition
      of polyethyleneimine (PEI) and alginate (ALG) and heparin blended with ALG was
      immobilized only on the outermost surface of the LBL assembly. The results have
      shown that the adsorption of human plasma proteins and platelet activation on the
      LBL modified membranes decreased significantly compared with the unmodified PSF
      and PSF-SPSF blend membranes. Furthermore, blending ALG with a small amount of
      heparin remarkably prolonged the APTT values of heparin free PEI/ALG coated
      membranes. It is envisaged that the use of a blend of HEP and ALG only in the
      terminating layer of the LBL assembly can be an economical and alternative
      modification technique to create nonthrombogenic surfaces.

PMID- 23128986
TI  - Insulinotropic action of Citrullus colocynthis seed extracts in rat pancreatic
      islets.
AB  - The present study aimed to investigate the direct in vitro effects of several
      distinct Citrullus colocynthis seed extracts on glucose-stimulated insulin
      release from pancreatic islets isolated from rats. Six extracts were tested, a
      crude aqueous, defatted aqueous, ethyl acetate, H2O-methanol and n-butanol
      extract and an extract containing a major component (fraction A) identified by
      gel chromatography in the ethyl acetate, n-butanol and H2O-methanol extracts.
      Under selected experimental conditions, the majority of extracts exhibited a
      positive insulinotropic action, at least when tested in the presence of 8.3 mM D
      glucose. The concentration-response correlation observed with distinct extracts
      revealed the participation of distinct chemical compounds, including compounds
      with an inhibitory insulinotropic potential, in the modulation of the insulin
      secretory response to D-glucose. The results of the present study are relevant
      for further investigations which aim to identify compounds exhibiting positive
      insulinotropic actions. These agents may be suitable for the treatment of human
      diabetic subjects. 

PMID- 23128988
TI  - Removal possibilities of colloidal chromium (III) oxide from water using
      polyacrylic acid.
AB  - The lack of water is the most serious threat to humanity that leads to more
      efficient water and sewage treatment. Currently, many scientists are looking for
      new coagulants, flocculants and physicochemical methods allowing for sufficient
      removal of pollutants from water. The presence of various types of pigments,
      including chromium (III) oxide, poses the major problem. Even small amounts of
      these substances inhibit life processes in water. In this paper, the stability of
      Cr2O3 suspension in the absence and the presence of polyacrylic acid (PAA) was
      determined. To explain the changes in the system stability, the adsorption and
      electrokinetic measurements were performed. The chromium (III) oxide suspension
      not containing PAA is the most stable at pH=3. Under these conditions, each
      positively charged solid particle is surrounded by a negatively charged diffusion
      layer which protects from particle collision and aggregates formation
      (electrostatic stabilization). In turn, the Cr2O3 suspension containing the PAA
      is most unstable also at pH=3. In this case, the polymer causes destabilization
      of the colloidal suspension, which results from charge neutralization of solid
      particles by adsorbed PAA.

PMID- 23128987
TI  - Cell-to-cell communication in plants, animals, and fungi: a comparative review.
AB  - Cell-to-cell communication is a prerequisite for differentiation and development
      in multicellular organisms. This communication has to be tightly regulated to
      ensure that cellular components such as organelles, macromolecules, hormones, or
      viruses leave the cell in a precisely organized way. During evolution, plants,
      animals, and fungi have developed similar ways of responding to this biological
      challenge. For example, in higher plants, plasmodesmata connect adjacent cells
      and allow communication to regulate differentiation and development. In animals,
      two main general structures that enable short- and long-range intercellular
      communication are known, namely gap junctions and tunneling nanotubes,
      respectively. Finally, filamentous fungi have also developed specialized
      structures called septal pores that allow intercellular communication via
      cytoplasmic flow. This review summarizes the underlying mechanisms for
      intercellular communication in these three eukaryotic groups and discusses its
      consequences for the regulation of differentiation and developmental processes.

PMID- 23128989
TI  - PFOS and PFC releases and associated pollution from a PFC production plant in
      Minnesota (USA).
AB  - Perfluorooctane sulfonate (PFOS) and PFOS-related substances have been listed as
      persistent organic pollutants in the Stockholm Convention. From August 2012,
      Parties to the Convention needed to address the use, storage, and disposal of
      PFOS-including production sites and sites where PFOS wastes have been deposited
      in their national implementation plans. The paper describes the pollution in
      Minnesota (USA) caused by the 3M Company at one of the largest
      per/polyfluorinated chemical (PFC) production facilities. From early 1950s until
      the end of 2002, when 3M terminated PFOS and perfluorooctanoic acid (PFOA)
      production, PFOS, PFOA, and other PFC production wastes were disposed around the
      plant and in local disposal sites. Discharges from the site and releases from
      deposits caused widespread contamination of ground and surface waters including
      local drinking water wells. Fish in the river downstream were contaminated with
      PFOS to levels that led to fish consumption advisories. Human exposures resulted
      from ingesting contaminated drinking water, requiring installation of water
      treatment facilities and alternate water supplies. The critical evaluation of the
      assessments done revealed a range of gaps in particular of human exposure where
      relevant exposure pathways including the entire exposure via food have not been
      taken into consideration. Currently, the exposure assessment of vulnerable groups
      such as children or Hmong minorities is inadequate and needs to be
      improved/validated by epidemiological studies. The assessment methodology
      described for this site may serve-with highlighted improvements-as a model for
      assessment of other PFOS/PFC production sites in the Stockholm Convention
      implementation.

PMID- 23128990
TI  - Destruction of halogen-containing pesticides by means of detonation combustion.
AB  - Pesticides that contain a halogen functional group have been destructed by means
      of detonative combustion. The following compounds were examined: (1) atrazine-2
      chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine-herbicide; (2) bromophos-O,4
      bromo-2,5-dichlorophenyl O,O-dimethyl phosphorothioate-insecticide; (3)
      chloridazon-5-amino-4-chloro-2-phenylopyridazin-3(2H)-one-herbicide; (4) linuron
      3-(3,4-dichlorophenyl)-1-metoxy-1-methylurea-herbicide; (5) metoxychlor-1,1,1
      trichloro-2,2-bis(4-metoxyphenyl)ethane-insecticide and acaricide; and (6)
      trichlorfon-dimethyl 2,2,2-trichloro-1-hydroxyethylphosphonate-insecticide.
      Explosive material has been produced on the basis of ammonium nitrate, which
      served as an oxidizer while the pesticides were used as fuels. Composition of the
      explosive was adjusted in such a way as to respect thermodynamic parameters.
      Detonative decomposition of the mixtures has been carried out in shot-holes pre
      drilled in soil. Efficiency of the pesticide decomposition has been examined with
      gas chromatography in order to determine pesticides residues in the environment.
      It was found that for some, the amount of pesticides in some compounds in the
      analyzed samples after decomposition was below the determination threshold of the
      applied method.

PMID- 23128991
TI  - Fenton-like degradation of nalidixic acid with Fe(3+)/H2O 2.
AB  - The Fenton-like degradation of nalidixic acid was studied in this work. The
      effects of Fe(3+) concentration and initial H(2)O(2) concentration were
      investigated. Increasing the initial H(2)O(2) concentration enhances the
      degradation and mineralization efficiency for nalidixic acid, while Fe(3+) shows
      an optimal concentration of 0.25 mM. A complete removal of nalidixic acid and a
      TOC removal of 28 % were achieved in 60 min under a reaction condition of
      [Fe(3+)] =0.25 mM, [H(2)O(2)] =10 mM, T=35  degrees C, and pH=3. LC-MS analysis
      technique was used to analyze the possible degradation intermediates. The
      degradation pathways of nalidixic acid were proposed according to the identified
      intermediates and the electron density distribution of nalidixic acid. The Fenton
      like degradation reaction of nalidixic acid mainly begins with the electrophilic
      attack of hydroxyl radical towards the C3 position which results in the ring
      opening reaction; meanwhile, hydroxyl radical attacking to the branched alkyl
      groups of nalidixic acid leads to the oxidation at the branched alkyl groups.

PMID- 23128992
TI  - Mechanisms of toxicity of triphenyltin chloride (TPTC) determined by a live cell
      reporter array.
AB  - Triphenyltin chloride (TPTC), which has been extensively used in industry and
      agriculture, can occur at concentrations in the environment sufficient to be
      toxic. Here, potency of TPTC to modulate genes in a library containing 1,820
      modified green fluorescent protein (GFP)-expressing promoter reporter vectors
      constructed from Escherichia coli K12 strains was determined. Exposure to TPTC
      resulted in 22 (fold change > 2) or 71 (fold change > 1.5) differentially
      expressed genes. The no observed transcriptional effect (NOTEC) and median
      transcriptional effect concentrations (TEC50) were determined to be 0.036 and
      0.45 mg/L in E. coli. These responses were 1,230 and 97 times more sensitive than
      the acute median effect concentration (EC50) required to inhibit growth of cells,
      which demonstrated that this live cell array represents a sensitive method to
      assess toxic potency of chemicals. The 71 differentially expressed genes could be
      classified into seven functional groups. Of all the altered genes, three groups
      which encoded for catalytic enzymes, regulatory proteins, and structural proteins
      accounted for 28 %, 18 %, and 14 % of all altered genes, respectively. The
      pattern of differential expression observed during this study was used to
      elucidate the mechanism of toxicity of TPTC. To determine potential relationships
      among genes that were changed greater than 2.0-fold by exposure to TPTC, a
      correlation network analysis was constructed, and four genes were related to
      aroH, which is the primary target for metabolic regulation of aromatic
      biosynthesis by feedback inhibition in bacteria. The genes rnC, cld, and glgS
      were selected as potential biomarkers for TPTC, since their expression was more
      than 2.0-fold greater after exposure to TPTC.

PMID- 23128993
TI  - Accumulation pattern and distribution of polycyclic aromatic hydrocarbons (PAHs)
      in liver tissues of seven species of birds from Ahmedabad, India, during 2005
      2007.
AB  - Concentrations of polycyclic aromatic hydrocarbons (PAHs) were measured in liver
      tissues of seven species of birds collected from Ahmedabad, India during 2005
      2007. All the samples collected were dead as victims of kite flying.
      Concentrations of ?PAHs in livers of birds were ranged from 110 +/- 32.6 ng/g wet
      wt (1,078 +/- 320 lipid wt) in common myna Acridotheres tristis to 382 +/- 90.1
      ng/g (2,388 +/- 563 lipid wt) in white-backed vulture. Statistically significant
      (p < 0.05) differences in ?PAHs were observed among species. However, year of
      collection and sex of birds did not show significant differences in
      concentrations of PAHs. The levels of ?PAHs measured in the present study species
      were higher than the levels documented for a number of avian species and were
      lower than those reported to have deleterious effects on survival or reproduction
      of birds. Presence of PAH residues in birds of Ahmedabad city show the continuous
      input of PAHs through environmental exposure. Although no threat is posed by any
      of the hydrocarbons detected, continuous monitoring of breeding colonies of birds
      is recommended in unpolluted reference sites as well as polluted sites. It is
      also the first account of a comprehensive analysis of PAHs in various species of
      birds in India. Therefore, the values reported in this study can serve as
      baseline values for future research.

PMID- 23128994
TI  - Pial arteriovenous fistula as a cause of bilateral thalamic hyperintensities--an
      unusual case report and review of the literature.
AB  - INTRODUCTION: Isolated bilateral thalamic congestion due to an arteriovenous
      malformation (AVM) is a rare entity. Few case reports of dural arteriovenous
      fistula associated with it have been reported in the literature. The association
      of pial arteriovenous fistula (pial AVF) with thalamic hyperintensities has never
      been described before. The pial AVF is a recently recognized lesion in which the
      multiple pial arterial feeders drain into a single venous channel without a nidus
      like in conventional AVM. In spite of being congenital in origin, these lesions
      may have expression in adulthood due to abrupt change in the venous drainage
      system. Successful management of pial AVF associated with bilateral thalamic
      hyperintensities is described here with review of the literature. CASE
      PRESENTATION: A 60-year-old man presented with rapidly progressive gait
      disturbance and cognitive decline. Magnetic resonance imaging (MRI) showed
      hyperintensities in the thalami on T2-weighted and fluid attenuated inversion
      recovery image. Digital subtraction angiography revealed a pial AVF near the
      splenium of corpus callosum. It had feeders from posterior choroidal arteries and
      drained into the vein of Galen through an abnormal mesencephalic vein. The
      stagnation and increase of pressure in the deep venous system led to congestion
      in the thalami. He was treated by partial transarterial embolization of the
      feeders followed by gamma knife therapy (GKT). The clinical symptoms and MRI
      improved rapidly after embolization and further reduction in shunt flow was
      observed after GKT. CONCLUSION: Strong suspicion of vascular malformation as a
      cause of bilateral thalamic hyperintensities helps in early detection. Such
      lesions like pial AVF presented here require active intervention by surgery or
      endovascular therapy. GKT is an important adjuvant in lesions refractory to
      either of them.

PMID- 23128995
TI  - Gold nanorods and their plasmonic properties.
AB  - Gold nanorods have been receiving extensive attention owing to their extremely
      attractive applications in biomedical technologies, plasmon-enhanced
      spectroscopies, and optical and optoelectronic devices. The growth methods and
      plasmonic properties of Au nanorods have therefore been intensively studied. In
      this review, we present a comprehensive overview of the flourishing field of Au
      nanorods in the past five years. We will focus mainly on the approaches for the
      growth, shape and size tuning, functionalization, and assembly of Au nanorods, as
      well as the methods for the preparation of their hybrid structures. The plasmonic
      properties and the associated applications of Au nanorods will also be discussed
      in detail.

PMID- 23128996
TI  - Management of nonneoplastic portal vein thrombosis in the setting of liver
      transplantation:  a systematic review.
AB  - BACKGROUND: Nonneoplastic portal vein thrombosis (PVT) is frequent in patients
      with cirrhosis who undergo liver transplantation (LT); however, data on its
      impact on outcome and strategies of management are sparse. METHODS: A systematic
      review of the literature was performed by analyzing studies that report on PVT in
      LT recipients and were published between January 1986 and January 2012. RESULTS:
      Of 25,753 liver transplants, 2004 were performed in patients with PVT (7.78%),
      and approximately half presented complete thrombosis.
      Thrombectomy/thromboendovenectomy was employed in 75% of patients; other
      techniques included venous graft interposition and portocaval hemitransposition.
      Overall, the presence of PVT significantly increased 30-day (10.5%) and 1-year
      (18.8%) post-LT mortality when compared to patients without PVT (7.7% and 15.4%,
      respectively). However, only complete PVT accounted for this increased mortality.
      Rethrombosis occurred in up to 13% of patients with complete PVT and in whom no
      preventative strategies were used, and was associated with increased morbidity
      and mortality. CONCLUSIONS: PVT is common in patients with cirrhosis undergoing
      LT, and it affects survival when it is complete, at least in the short term after
      transplant. Therefore, screening for this condition is essential, alongside
      adequate treatment strategies to attempt repermeation of the PV and prevent
      thrombosis extension.

PMID- 23128997
TI  - Ratio of T helper to regulatory T cells in synovial fluid and postoperative joint
      laxity after allograft anterior cruciate ligament reconstruction.
AB  - BACKGROUND: Arthroscopic anterior cruciate ligament (ACL) reconstruction with
      allograft may vary in instrumented laxity compared with autograft. T helper (Th)
      cells (CCR4+CCR6+Th) and regulatory T (Treg) cells are important in the early
      stage of immunologic reactions. It is unknown whether the ratio of CCR4+CCR6+Th
      to Treg is imbalanced and if it correlates with early postoperative laxity after
      ACL allograft reconstruction. We investigated the ratio and functional influence
      between these cells and the correlation with postoperative anterior knee laxity.
      METHODS: In 40 patients who experienced unilateral arthroscopy-assisted ACL
      reconstruction, the ACL graft was an allograft in 20 patients and autograft in 20
      patients. Maximum manual anterior tibiofemoral laxity measurements were performed
      with arthrometry testing. The phenotypes of CCR4+CCR6+Th and Treg cells of
      peripheral blood and synovial fluid from the two patient groups were determined
      by flow cytometry. The functionality of isolated Treg cells and effector T cells
      was quantified in (3)H-thymidine proliferation assays. RESULTS: Both CCR4+CCR6+Th
      and Treg cells were significantly increased in the synovial fluid in the
      allograft group and were correlated with anterior knee laxity. The ratio of
      CCR4+CCR6+Th to Treg cells in the synovial fluid was positively correlated with
      laxity. Synovial CD4+CD25+ Treg cells displayed an increased suppressive capacity
      compared with blood CD4+CD25+ Treg cells. Activated responder T cells from the
      synovial fluid were less susceptible to CD4+CD25+ T cell-mediated suppression
      than were responder cells from blood. CONCLUSIONS: The ratio of CCR4+CCR6+Th to
      Treg cells in the synovial fluid was correlated with anterior laxity after ACL
      allograft reconstruction.

PMID- 23128998
TI  - A syndrome of severe hypoglycemia and acidosis in young immunosuppressed diabetic
      monkeys and pigs-association with sepsis.
AB  - BACKGROUND: Large animals treated with immunosuppressive drugs for preclinical
      experiments of transplantation have increased risks of infection, which can be
      compounded by the induction of diabetes if islet transplantation is planned.
      METHODS: We report our experience with severe sepsis in two young cynomolgus
      monkeys and five pigs that were subjected to diabetes induction,
      immunosuppressive therapy, or islet allotransplantation. RESULTS: In two monkeys
      and five pigs, infection was associated with a syndrome of profound hypoglycemia
      accompanied by severe acidosis, which was resistant to treatment. We do not
      believe that this syndrome has been reported previously by others. CONCLUSIONS:
      Despite treatment, this syndrome complicated the interpretation of blood glucose
      readings as a measure of islet graft function and resulted in death or the need
      for euthanasia in all seven animals. We tentatively suggest that the syndrome may
      be related to the presence of microorganisms that metabolize glucose and produce
      lactate.

PMID- 23128999
TI  - Donor selection for adult-to-adult living donor liver transplantation: well begun
      is half done.
AB  - BACKGROUND: Donor selection criteria for adult-to-adult living donor liver
      transplantation vary with the medical center of evaluation. Living donor
      evaluation uses considerable resources, and the nonmaturation of potential into
      actual donors may sometimes prove fatal for patients with end-stage liver
      disease. On the contrary, a thorough donor evaluation process is mandatory to
      ensure safe outcomes in otherwise healthy donors. We aimed to study the reasons
      for nonmaturation of potential right lobe liver donors at our transplant center.
      METHODS: A retrospective data analysis of all potential living liver donors
      evaluated at our center from 1998 to 2010 was done. RESULTS: Overall, 324 donors
      were evaluated for 219 potential recipients, and 171 (52.7%) donors were
      disqualified. Common reasons for donor nonmaturation included the following: (1)
      donor reluctance, 21%; (2) greater than 10% macro-vesicular steatosis, 16%; (3)
      assisted donor withdrawal, 14%; (4) inadequate remnant liver volume, 13%; and (5)
      psychosocial issues, 7%, and thrombophilia, 7%. Ten donors (6%) were turned down
      because of anatomic variations (8 biliary and 2 arterial anomalies). Donors older
      than 50 years and those with body mass index of more than 25 were less likely to
      be accepted for donation. CONCLUSIONS: We conclude that donor reluctance, hepatic
      steatosis, and assisted donor withdrawal are major reasons for nonmaturation of
      potential into actual donors. Anatomic variations and underlying medical
      conditions were not a major cause of donor rejection. A system in practice to
      recognize these factors early in the course of donor evaluation to improve the
      efficiency of the selection process and ensure donor safety is proposed.

PMID- 23129002
TI  - Pattern of pediatric dermatoses at a referral centre.
AB  - OBJECTIVE: To determine the pattern of skin disorders seen among children
      attending a Medical College Hospital, Bangalore METHODS: All children 18 y and
      below attending the Pediatric Dermatology OPD with skin diseases between the
      period of January 2011 and June 2011 were included in the study. RESULTS: A total
      of 1,090 new cases (boys 589; girls 501) with 1,118 dermatoses were recorded
      during this period. Twenty eight children had more than one dermatoses. Most of
      the disorders were seen between 5 and 11 y age group. The most common dermatoses
      was infections and infestations (32.47 %) followed by eczematous eruptions and
      dermatitis (20.66 %), papulosquamous and related disorders (6.08 %) and
      pigmentary disorders (5.81 %). Insect bite reactions and papular urticaria formed
      5.1 %. Acne was seen in 5.28 % of children followed by urticaria (3.67 %),
      photodermatoses 2.5 % and genetic disorders (3.04 %). CONCLUSIONS: In the present
      setting bacterial infections and scabies still remained the most common pediatric
      dermatoses followed by molluscum contagiosum and atopic dermatitis. Childhood
      psoriasis contributed to major part of the study among papulosquamous disorders.

PMID- 23129003
TI  - Perioperative management of patients undergoing pancreatic resection:
      implementation of a care plan in a tertiary-care center.
AB  - Evidence-based perioperative management is important for a successful outcome
      after pancreatic surgery. Use of protocolized pathways of care based on fast
      track concepts has been shown to reduce hospital stay and contain costs. These
      regimens include pain control, early device removal (nasogastric tube, abdominal
      drains), enforced early mobilization, and early oral feeding. In this article,
      current evidence on perioperative management of pancreatic resections was
      analyzed in the attempt to implement our institutional care plan.

PMID- 23129001
TI  - Indicated prevention of adult obesity: how much weight change is necessary for
      normalization of weight status in children?
AB  - OBJECTIVE: To investigate the notion of indicated prevention-helping overweight
      or obese youth attain non-overweight status to prevent adult obesity-by examining
      weight-for-height changes needed to normalize weight status in youth who are
      growing. DESIGN: We determined the amount of weight-for-height change necessary
      for overweight or obese youth to achieve non-overweight status using linear mixed
      modeling of longitudinal growth patterns and using Centers for Disease Control
      and Prevention weight thresholds corresponding to the age- and sex-adjusted body
      mass index (BMI; calculated as weight in kilograms divided by height in meters
      squared) below the 85th percentile. Mean weight changes among children who
      achieved nonoverweight status at 1 and 2 years after treatment were calculated.
      SETTING: Weight control programs at 3 research institutions. PARTICIPANTS: A
      total of 669 overweight or obese children aged 8 to 13 years. INTERVENTION:
      Family-based behavioral weight control treatment. MAIN OUTCOME MEASURE: Weight.
      RESULTS: Relatively small weight changes (range, -7.55 to +3.90 kg) were
      necessary for children to achieve nonoverweight status after 1 year; this was
      most pronounced among younger children (range, -2.90 to +3.36 kg for children
      aged 8-10 years) and children closer to the 85th BMI percentile (range, +2.44 to
      +3.90 kg for children at the 90th BMI percentile). Observed weight changes of
      children who achieved nonoverweight status following treatment were similar to
      estimates based on Centers for Disease Control and Prevention normative data.
      CONCLUSIONS: Attaining nonoverweight status in childhood is possible with modest
      weight loss or, in some circumstances, by slowing weight gain, and may help
      prevent adult obesity. Future research should investigate how much intervention
      is needed to shift the growth trajectory to nonoverweight status and how much
      weight-for-height change is needed to improve other health outcomes in adulthood.

PMID- 23129000
TI  - Costimulation blockade:  current perspectives and implications for therapy.
AB  - T cells must be activated before they can elicit damage to allografts, through
      interaction of their T cell receptor (TCR) with peptide-MHC complex and through
      accessory molecules. Signaling through accessory molecules or costimulatory
      molecules is a critical way for the immune system to fine tune T cell activation.
      An emerging therapeutic strategy is to target selective molecules involved in the
      process of T cell activation using biologic agents, which do not impact TCR
      signaling, thus only manipulating the T cells, which recognize alloantigen.
      Costimulatory receptors and their ligands are attractive targets for this
      strategy and could be used both to prevent acute graft rejection as well as for
      maintenance immunosuppression. Therapeutic agents targeting costimulatory
      molecules, notably belatacept, have made the progression from the bench, through
      nonhuman primate studies and into the clinic. This overview describes some of the
      most common costimulatory molecules, their role in T cell activation, and the
      development of reagents, which target these pathways and their efficacy in
      transplantation.

PMID- 23129004
TI  - Luteolin inhibition of V-ATPase a3-d2 interaction decreases osteoclast resorptive
      activity.
AB  - V-ATPase-mediated acid secretion is required for osteoclast bone resorption.
      Osteoclasts are enriched in V-ATPase a3 and d2 subunit isoforms, and disruption
      of either of their genes impairs bone resorption. Using purified fusion proteins
      of a3 N-terminal domain (NTa3) and full-length d subunits we determined in a
      solid-phase binding assay that half-maximal binding of d1 or d2 to immobilized
      NTa3 occurs at 3.1 +/- 0.4 or 3.6 +/- 0.6 nM, respectively, suggesting equally
      high-affinity interactions. A high-throughput modification of this assay was then
      used to screen chemical libraries for a3-d2 interaction inhibitors, and luteolin,
      a naturally occurring flavonoid, was identified, with half-maximal inhibition at
      2.4 +/- 0.9 uM. Luteolin did not significantly affect NIH/3T3 or RAW 264.7 cell
      viability, nor did it affect cytokine-induced osteoclastogenesis of RAW 264.7
      cells or bone marrow mononuclear cells at concentrations <= 40 uM. Luteolin
      inhibited osteoclast bone resorption with an EC(50) of approximately 2.5 uM,
      without affecting osteoclast actin ring formation. Luteolin-treated osteoclasts
      produced deeper resorption pits, but with decreased surface area, resulting in
      overall decreased pit volume. Luteolin did not affect transcription, or protein
      levels, of V-ATPase subunits a3, d2, and E, or V(1) V(0) assembly. Previous work
      has shown that luteolin can be effective in reducing bone resorption, and our
      studies suggest that this effect of luteolin may be through disruption of
      osteoclast V-ATPase a3-d2 interaction. We conclude that the V-ATPase a3-d2
      interaction is a viable target for novel anti-resorptive therapeutics that
      potentially preserve osteoclast-osteoblast signaling important for bone
      remodeling.

PMID- 23129006
TI  - Evaluation of the visual function in obstructive sleep apnea syndrome patients
      and normal-tension glaucoma by means of the multifocal visual evoked potentials.

PMID- 23129005
TI  - Results of excimer laser penetrating keratoplasty in aphakic eyes.
AB  - BACKGROUND: Corneal grafting in aphakic eyes is often challenging. We report
      about the outcome of excimer laser trephination in aphakic eyes. METHODS: We
      examined 17 eyes of 17 patients. Diagnosis in 11 eyes was endothelial
      decompensation and in six, corneal scars. We performed an excimer laser
      keratoplasty with intraoperative "Flieringa ring" suturing. Follow-up ranged
      between 3 and 41 (17.6 +/- 11.7) months. Main outcome measures included: best
      corrected visual acuity (BCVA), intraocular pressure (IOP), topographic
      astigmatism, corneal refractive power (CRP), central corneal thickness (CCT) and
      endothelial cell density (ECD). RESULTS: Preoperative BCVA was light perception
      in two eyes, hand motion in seven, finger counting in one eye, under 20/400 in
      six eyes and 20/200 in one eye. IOP ranged between 4 and 28 (13.6 +/- 5.1) mmHg.
      Topographic astigmatism ranged from 0.5 to 18.5 (7.0 +/- 6.9) dioptres. CRP was
      between 38 and 59 (46 +/- 9) dioptres. CCT was between 404 and 1069 (748 +/- 181)
      MUm. Postoperative BCVA was hand motion in five eyes, under 20/400 in two and
      ranged between 20/200 and 20/20 in ten eyes. IOP ranged between 10 and 40 (18.3
      +/- 8.5) mmHg. Topographic astigmatism ranged from 0.9 to 13 (5.5 +/- 3.2)
      dioptres. CRP was between 31.9 and 46.7 (42 +/- 4.1) dioptres. CCT was between
      349 and 820 (552 +/- 115.57) MUm. ECD was between 592 and 2319 (1674 +/- 553)
      cells/mm(2). CONCLUSIONS: Excimer laser trephination can deliver beneficial
      visual outcomes in most of the aphakic eyes.

PMID- 23129007
TI  - Multifocal electroretinography in type 2 idiopathic macular telangiectasia.
AB  - BACKGROUND: To characterize the electroretinographic response of the macula by
      multifocal electroretinography (mfERG) in patients with type 2 idiopathic macular
      telangiectasia (MacTel). METHODS: A prospective study of mfERG in patients with
      type 2 MacTel was conducted from April 2009 to November 2009. mfERGs were
      recorded using a visual evoked response imaging system (MonElec2, Metrovision,
      Perenchies, France). The International Society for Clinical Electrophysiology of
      Vision (ISCEV) guidelines were followed. Patients with type 2 MacTel confirmed by
      fundus fluorescein angiography without subretinal neovascularisation were
      included. For recording purposes, 61 stimulus hexagonal elements were used. The
      first-order kernel mfERG responses were analyzed. Individual mfERG responses for
      the hexagons were grouped into concentric rings centered on the fovea for
      analysis (< 2, 5-10, 10-15 and >15 degrees ). Student's t-test and Mann-Whitney U
      test and linear regression analysis was performed with STATA ver 11.1 (StataCorp,
      College Station , TX, USA). RESULTS: Twenty eight eyes of 14 patients and 20 eyes
      of ten normal controls were included in the study. The mean logMAR visual acuity
      of the patients was 0.51 (Snellen equivalent 20/63). The mean N1 amplitude
      (nv/deg(2)) of patients were significantly reduced compared to controls and were
      as follows: 8.91 +/- 14.00 vs 43.44 +/- 9.55 (p < 0.0001) in less than 2 degrees
      , 9.24 +/- 10.47 vs 22.00 +/- 3.87 (p < 0.0001) in 5-10 degrees , 8.57 +/- 10.02
      vs 15.24 +/- 1.89 (p < 0.0001) in 10-15 degrees , and 7.03 +/- 6.52 vs 12.47 +/-
      2.62 in > 15 degrees  (p < 0.001). The mean P1 amplitude (nv/deg(2)) was also
      significantly reduced in patients compared to controls and was as follows: 27.66
      +/- 37.44 vs 96.20 +/- 12.41 (p < 0.0001) in less than 2 degrees , 22.61 +/-
      19.38 vs 53.78 +/- 9.79 (p < 0.0001) in 5-10 degrees , 18.75 +/- 20.21 vs 35.22
      +/- 4.16 (p < 0.001) in 10-15 degrees , and 17.10 +/- 12.54 vs 25.71 +/- 3.93 (p
      < 0.001). The implicit time of N1 and P1 were also delayed significantly in all
      the rings. The mean central foveal thickness assessed by optical coherence
      tomography (OCT) scan was 84.78 +/- 45.12 MUm. There was poor correlation between
      mfERG amplitudes or implicit times with either the visual acuity or OCT central
      thickness. CONCLUSION: mfERG showed significant reduction in amplitudes and
      implicit times of the waveforms in patients with type 2 MacTel in all the rings,
      suggesting a more generalized affection of the macula. The maximum reductions
      were seen in the <2(o) rings. Although there was poor correlation between the
      visual acuity and the amplitudes a of the waveforms, mfERG is a useful
      investigative modality for functional assessment of macula in type 2 MacTel
      patients.

PMID- 23129009
TI  - Increased carboxyhemoglobin level during liver resection with inflow occlusion.
AB  - Controlling stress responses associated with ischemic changes due to bleeding and
      ischemia/reperfusion injury is essential for anesthetic management. Endogenous
      carboxyhemoglobin (COHb) is produced in the oxidative degradation of heme
      proteins by the stress-response enzyme heme oxygenase. Although the COHb level is
      elevated in critically ill patients, changes in endogenous COHb during anesthesia
      have not been well investigated. Therefore, we evaluated changes in endogenous
      COHb levels in patients undergoing liver resections with inflow occlusion. Levels
      of COHb were significantly increased after the Pringle maneuver. The inflow
      occlusion time in patients with increased COHb after the Pringle maneuver (?COHb
      > 0.3 %) was significantly longer than in patients without increased COHb (?COHb
      < 0.3 %) (P = 0.01). In addition, COHb changes were correlated with inflow
      occlusion time (P = 0.005, R(2) = 0.21). Neither total blood loss, transfusion
      volume of packed red blood cells, operation time, nor anesthetic time differed
      between patients with and without increased COHb. The results indicated that
      endogenous COHb levels were increased by inflow occlusion in patients undergoing
      liver resections, which suggests that changes in COHb may correlate with hepatic
      ischemia/reperfusion injury induced by inflow occlusion.

PMID- 23129010
TI  - Pyrrole versus quinoline formation in the palladium catalyzed reaction of 2
      alkynyl-3-bromothiophenes and 2-alkynyl-3-bromofurans with anilines. A combined
      experimental and computational study.
AB  - Benzofuroquinolines were prepared by a new type of Pd catalyzed annulation
      reaction. In the first step, 2-alkynyl-3-bromobenzofurans were prepared by
      Sonogashira reactions of 2,3-dibromobenzofuran. Their Pd catalyzed reaction with
      electron-rich anilines afforded benzofuroquinolines by a domino C-N
      coupling/annulation process. This reaction proceeds as a C,N-cyclization via the
      nitrogen atom and the ortho-carbon of the aniline. Similarly, furoquinolines were
      prepared from 2,3-dibromofuran. In contrast, benzofuropyrroles and furopyrroles
      were formed by N,N-cyclization when electron-poor anilines were used. Earlier, we
      reported results related to the thiophene and benzothiophene series. Quinolines
      were formed from 2,3-dibromobenzothiophene when electron rich anilines were used.
      In contrast, pyrroles were obtained in the case of electron-poor anilines. On the
      other hand, pyrroles were generally obtained, not depending on the type of
      aniline, when 2,3-dibromothiophene was employed as the starting material. In the
      present article, a detailed DFT study related to the mechanism (quinoline versus
      pyrrole formation) is reported which provides a rationalization of the
      selectivities observed for the furan, benzofuran, thiophene and benzothiophene
      series and for the different selectivities observed for electron-rich and -poor
      anilines.

PMID- 23129011
TI  - Miniature asymmetric ultracapacitor of patterned carbon nanotubes and hydrous
      ruthenium dioxide.
AB  - A symmetric ultracapacitor CNT_CNT and an asymmetric ultracapacitor CNT_hRuO(2)
      of mini size have been prepared with patterned carbon nanotubes (CNT) and hydrous
      ruthenium dioxide. Galvanostatic charge/discharge results indicate that
      CNT_hRuO(2) is the superior one in both power and energy densities. In a
      potential window 2.0 V, the CNT_hRuO(2) cell displays an energy density of 24.0 W
      h kg(-1) at a power density of 22.9 kW kg(-1). Its power density can be raised to
      41.1 kW kg(-1) at the expense of the energy density, which drops to 6.8 W h kg(
      1). On the other hand, CNT_CNT performs at a lower level, delivering 5.2 W h kg(
      1) at 5.5 kW kg(-1). The favorable charge/discharge performance of CNT_hRuO(2) is
      attributed to hydrous RuO(2), whose pseudocapacitance drives the other electrode
      of the vertical CNT array to work harder and makes more use of its double-layer
      capacitance. The analysis of individual electrode capacitance indicates that the
      high capacitance of hRuO(2) also causes a disproportion in voltage partition,
      which restricts the low limit of cycling current in an extended potential window.
      On energy cycling, CNT_hRuO(2) demonstrates sufficient stability in 10,000
      cycles, after an initial 13% drop in capacitance.

PMID- 23129012
TI  - NMR structure note: repetitive domain of aciniform spidroin 1 from Nephila
      antipodiana.

PMID- 23129014
TI  - Testing effects of community collaboration on rates of low infant birthweight at
      the county level.
AB  - Interorganizational collaboration has become a popular strategy for addressing
      population health and well-being. However, evidence for its effectiveness in
      achieving outcomes at the population level is limited, at least in part due to a
      variety of methodological challenges such as reduced sample size at the
      population level, the availability of suitable comparison groups of communities,
      and study durations that are too short to detect slowly emerging outcomes. The
      present study addresses these challenges by retrospectively examining the
      effectiveness of a mature network of community collaboratives, using latent
      growth modeling of longitudinal change in an archival community-level outcome,
      low infant birthweight, and propensity score matching of comparison communities.
      A group of 25 Georgia counties with collaboratives targeting low infant
      birthweight was compared to a weighted comparison group of counties from other
      southeastern states, using propensity score matching. We report results of full
      matching methods and outcome analyses examining differences in change in county
      rates of low infant birthweight from 1997 to 2004 between intervention and
      comparison counties. Results indicated significantly smaller increases in low
      weight birth rates in intervention counties than in comparison counties.

PMID- 23129008
TI  - Effect of the use and timing of bone marrow mononuclear cell delivery on left
      ventricular function after acute myocardial infarction: the TIME randomized
      trial.
AB  - CONTEXT: While the delivery of cell therapy after ST-segment elevation myocardial
      infarction (STEMI) has been evaluated in previous clinical trials, the influence
      of the timing of cell delivery on the effect on left ventricular function has not
      been analyzed. OBJECTIVES: To determine the effect of intracoronary autologous
      bone marrow mononuclear cell (BMC) delivery after STEMI on recovery of global and
      regional left ventricular function and whether timing of BMC delivery (3 days vs
      7 days after reperfusion) influences this effect. DESIGN, SETTING, AND PATIENTS:
      A randomized, 2 * 2 factorial, double-blind, placebo-controlled trial, Timing In
      Myocardial infarction Evaluation (TIME) enrolled 120 patients with left
      ventricular dysfunction (left ventricular ejection fraction [LVEF] <= 45%) after
      successful primary percutaneous coronary intervention (PCI) of anterior STEMI
      between July 17, 2008, and November 15, 2011, as part of the Cardiovascular Cell
      Therapy Research Network sponsored by the National Heart, Lung, and Blood
      Institute. INTERVENTIONS: Intracoronary infusion of 150 * 106 BMCs or placebo
      (randomized 2:1) within 12 hours of aspiration and cell processing administered
      at day 3 or day 7 (randomized 1:1) after treatment with PCI. MAIN OUTCOME
      MEASURES: The primary end points were change in global (LVEF) and regional (wall
      motion) left ventricular function in infarct and border zones at 6 months
      measured by cardiac magnetic resonance imaging and change in left ventricular
      function as affected by timing of treatment on day 3 vs day 7. The secondary end
      points included major adverse cardiovascular events as well as changes in left
      ventricular volumes and infarct size. RESULTS: The mean (SD) patient age was 56.9
      (10.9) years and 87.5% of participants were male. At 6 months, there was no
      significant increase in LVEF for the BMC group (45.2% [95% CI, 42.8% to 47.6%] to
      48.3% [95% CI, 45.3% to 51.3%) vs the placebo group (44.5% [95% CI, 41.0% to
      48.0%] to 47.8% [95% CI, 43.4% to 52.2%]) (P = .96). There was no significant
      treatment effect on regional left ventricular function observed in either infarct
      or border zones. There were no significant differences in change in global left
      ventricular function for patients treated at day 3 (-0.9% [95% CI, -6.6% to
      4.9%], P = .76) or day 7 (1.1% [95% CI, -4.7% to 6.9%], P = .70). The timing of
      treatment had no significant effect on regional left ventricular function
      recovery. Major adverse events were rare among all treatment groups. CONCLUSION:
      Among patients with STEMI treated with primary PCI, the administration of
      intracoronary BMCs at either 3 days or 7 days after the event had no significant
      effect on recovery of global or regional left ventricular function compared with
      placebo. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00684021.

PMID- 23129016
TI  - Pneumosinus dilatans in anterior skull base meningiomas.
AB  - INTRODUCTION: Skull base meningiomas are often missed on non-contrast CT or MR
      examinations due to their close proximity to bone and low lesion to brain
      contrast. The purpose of this study is to illustrate that pneumosinus dilatans
      can be an indicator of anterior skull base meningiomas. METHODS: A retrospective
      search of the radiology information system and picture archiving and computing
      system database was performed. Search terms were "meningioma" in association with
      "pneumosinus dilatans." Medical records and imaging studies were reviewed
      independently by two experienced neuroradiologists and were read in consensus. We
      recorded the patient age at the time of discovery of the meningioma, main
      presenting symptom(s), location of the tumor, and imaging characteristics. We
      also performed a comparative literature search for pneumosinus dilatans and its
      association with meningiomas. RESULTS: Ten patients (six women; four men) were
      identified in whom a meningioma of the anterior skull base was associated with a
      pneumosinus dilatans. Three patients had multiple meningiomas, so a total of 14
      intracranial tumors were identified. Mean age at discovery was 59 years with an
      age range of +/- 20years. All meningiomas were diagnosed by MRI and/or CT.
      CONCLUSION: Pneumosinus dilatans can be a helpful sign to indicate the presence
      of a meningioma of the anterior skull base.

PMID- 23129015
TI  - Advanced glycation end-products stimulate basic fibroblast growth factor
      expression in cultured Muller cells.
AB  - Accumulating evidence points to a causal role for advanced glycation end-products
      (AGEs) in the development of diabetic vascular complications, including diabetic
      retinopathy (DR). To assess the reciprocal correlation between AGEs and basic
      fibroblast growth factor (bFGF), the effects of AGEs on the production of bFGF by
      Muller cells were investigated. Muller cells were cultured from adult rabbit
      retinas. The AGEs were prepared with highly glycated bovine serum albumin (BSA)
      and the control non-glycated BSA (BSA control) was incubated under the same
      conditions without glucose. Cultured Muller cells were exposed to AGEs or BSA
      control (volume percentages were 4, 8, 16, 32 and 64%) for a time course of 1, 3,
      6 and 9 days in their desired medium. The expression of bFGF in Muller cells was
      evaluated by immunocytochemistry. Quantification was performed by densitometry
      using computerized image analysis with dedicated software. AGEs in a volume
      percentage of 16 and 32% on day 1 and in a volume percentage of 16, 32 and 64% on
      days 3, 6 and 9 increased the bFGF expression in Muller cells (P<0.05).
      Additionally, AGEs upregulated bFGF expression in Muller cells in a time
      dependent manner. In conclusion, the treatment of Muller cells with AGEs resulted
      in a dose- and time-dependent elevation of bFGF in the culture medium. The
      results from this study suggest that the increased formation of AGEs in the
      vitreous may be involved in the development of DR by inducing the production of
      bFGF by retinal Muller cells. 

PMID- 23129017
TI  - Testicular orphan nuclear receptor 4-associated protein 16 promotes non-small
      cell lung carcinoma by activating estrogen receptor beta and blocking testicular
      orphan nuclear receptor 2.
AB  - The possible involvement of estrogen receptors (ERs) and testicular orphan
      nuclear receptors (TRs) in human non-small cell lung carcinoma (NSCLC) has been
      suggested, but their precise roles and their relationship remain largely unknown.
      This study aimed to investigate whether TR4-associated protein 16 (TRA16)
      regulates the ERbeta and TR2 pathways and could be a potential target in NSCLC.
      We used tissue microarrays including NSCLC tissues (n=154) and negative controls
      (n=14) to examine the expression of TRA16 and ERbeta, and in vitro reporter gene
      assays, the mammalian two-hybrid method and immunoprecipitation in Cos-1 cells to
      investigate the relationships among TRA16, ERbeta and TR2. We found that TRA16
      was highly expressed in approximately 90% of the NSCLC tissues examined. TRA16
      overexpression was significantly associated with TNM stage, tumor size, lymph
      node metastasis, tumor thrombus in vein, tumor differentiation and prognosis of
      NSCLC patients, in which TRA16 was shown to be an independent prognostic factor.
      Introduction of TRA16 into Cos-1 cells enhanced cell proliferation. Co-expression
      of TRA16 and ERbeta in Cos-1 cells using different reporter gene systems and
      mammalian two-hybrid approaches revealed that TRA16 enhanced ERbeta-mediated
      transcriptional activity. By adopting similar approaches, and immunoprecipitation
      and immunocytofluorescence assays, we found that TRA16 also interacted with TR2,
      and blocked the TR2 inhibitory effect on ERbeta. Our findings demonstrate that
      TRA16 could be a promising diagnostic and prognostic biomarker in NSCLC, and
      promotes cancer cell growth through activation of the ERbeta pathway by
      interacting with ERbeta and TR2.

PMID- 23129018
TI  - Electroacupuncture promotes neurological functional recovery via the retinoic
      acid signaling pathway in rats following cerebral ischemia-reperfusion injury.
AB  - Neurogenesis is regulated by a number of signaling pathways, including the
      retinoic acid (RA) pathway, a key regulator of neurogenesis in the subventricular
      zone (SVZ) and hippocampus. Acupuncture has been used to treat neurological
      conditions and is known to potentially enhance cell proliferation in the
      neurogenic area (hippocampal dentate gyrus and the SVZ of the lateral ventricle
      walls) in pathological conditions, which is associated with improved brain
      function. However, whether or not the neuroprotective effects of
      electroacupuncture (EA) are mediated by the regulation of the RA signaling
      pathway remains to be determined. Using a transient middle cerebral artery
      occlusion model, in the present study we evaluated the effect of EA on the
      neurological functional recovery, infarction volume and investigated the
      underlying molecular mechanisms. Two hundred and sixteen SD rats were randomly
      divided into 3 groups: sham, model group (ischemic rats without EA stimulation)
      and EA group (ischemic rats with EA stimulation on ST36 and LI11). Behavioral
      deficits were detected with high-resolution digital analysis of 24-h home-cage
      video recordings. Infarct volume was determined by triphenyltetrazolium
      hydrochloride staining and the expression of RA mRNA and protein was measured
      using RT-PCR and western blotting, respectively. We found that EA decreased the
      infarct volume, promoted neurological functional recovery and increased the RA
      mRNA and protein expression, compared with the model group. Findings of this
      study suggest that promoting neurological functional recovery by modulating RA
      expression in the post-ischemic brain is one of the mechanisms by which EA can be
      effective in the treatment of ischemic stroke.

PMID- 23129020
TI  - Mild reduction of carbon dioxide to methane with tertiary silanes catalyzed by
      platinum and palladium silyl pincer complexes.

PMID- 23129019
TI  - Toxicity of engineered nanomaterials: a physicochemical perspective.
AB  - The global market for nanomaterial-based products is forecasted to reach 100
      billion dollars per annum for 2011-2015. Extensive manufacturing and the use of
      engineered nanomaterials have raised concerns regarding their impact on
      biological response in living organisms and the environment at large. The
      fundamental properties of nanomaterials exhibit a complex dependence upon several
      factors such as their morphology, size, defects, and chemical stability.
      Therefore, it is exceedingly difficult to correlate their biological response
      with their intricate physicochemical properties. For example, varying toxic
      response may ensue due to different methods of nanomaterial preparation,
      dissimilar impurities, and defects. In this review, we surveyed the existing
      literature on the dependence of cytotoxicity on physicochemical properties. We
      found that ENM size, shape, defect density, physicochemical stability, and
      surface modification to be the main causes that elicit altered physiological
      response or cytotoxicity.

PMID- 23129021
TI  - The SHED-IT community trial: a randomized controlled trial of internet- and paper
      based weight loss programs tailored for overweight and obese men.
AB  - BACKGROUND: There is limited evidence for effective obesity treatment programs
      that engage men. PURPOSE: This study evaluated the efficacy of two gender
      tailored weight loss interventions for men, which required no face-to-face
      contact. METHODS: This was a three-arm, randomized controlled trial: (1)
      Resources (n = 54), gender-tailored weight loss materials (DVD, handbooks,
      pedometer, tape measure); (2) Online (n = 53), Resources materials plus study
      website and e-feedback; and (3) Wait-list control (n = 52). The interventions
      lasted 3 months and were grounded in Social Cognitive Theory. RESULTS: At 6
      months, significantly greater weight loss was observed for the Online (-4.7 kg;
      95 % CI -6.1, -3.2) and Resources (-3.7 kg; 95 % CI -4.9, -2.5) groups compared
      to the control (-0.5 kg; 95 % CI -1.4, 0.4). Additionally, both intervention
      groups significantly improved body mass index, percent body fat, waist
      circumference, blood pressure, physical activity, quality of life, alcohol risk,
      and portion size, compared to controls. CONCLUSIONS: Men achieved significant
      weight loss after receiving novel, minimal-contact, gender-tailored programs,
      which were designed for widespread dissemination.

PMID- 23129023
TI  - Effective regioselective protection of amino groups of lysine achieved by a
      supramolecular enzyme-mimic approach.
AB  - An enzymic method to protect selected amino group of lysine has been reported.
      This reaction proceeds smoothly under room temperature with high regioselectivity
      (up to 99%) and high yields (up to 90%). This work will pave the way for simple
      and selective protection of amino group of lysine in industry.

PMID- 23129022
TI  - Improved performance of nanowire-quantum-dot-polymer solar cells by chemical
      treatment of the quantum dot with ligand and solvent materials.
AB  - We report a nanowire-quantum-dot-polymer solar cell consisting of a chemically
      treated CdSe quantum dot film deposited on n-type ZnO nanowires. The electron and
      hole collecting contacts are a fluorine-doped tin-oxide/zinc oxide layer and a
      P3HT/Au layer. This device architecture allows for enhanced light absorption and
      an efficient collection of photogenerated carriers. A detailed analysis of the
      chemical treatment of the quantum dots, their deposition, and the necessary
      annealing processes are discussed. We find that the surface treatment of CdSe
      quantum dots with pyridine, and the use of 1,2-ethanedithiol (EDT) ligands,
      critically improves the device performance. Annealing at 380  degrees C for 2 h
      is found to cause a structural conversion of the CdSe from its initial isolated
      quantum dot arrangement into a polycrystalline film with excellent surface
      conformality, thereby resulting in a further enhancement of device performance.
      Moreover, long-term annealing of 24 h leads to additional increases in device
      efficiency. Our best conversion efficiency reached for this type of cell is 3.4%
      under 85 mW cm(-2) illumination.

PMID- 23129024
TI  - Brain iron deposition in white matter hyperintensities: a 3-T MRI study.
AB  - Iron accumulation has been implicated in the pathogenesis of demyelinating
      diseases. Therefore, we hypothesized that abnormal high cerebral iron deposition
      may be involved in the development of white matter hyperintensities (WMHs). We
      used R2* relaxometry to assess whether iron levels in different brain regions
      correlate with the severity of WMHs. This technique has been recently validated
      in a postmortem study to demonstrate in vivo brain iron accumulation in a
      quantitative manner. Fifty-two consecutive WMH patients and 30 healthy controls
      with 3-T magnetic resonance imaging (MRI) were reviewed in this study. We
      measured WMH volume (as a marker of the severity of WMHs) on MRI, and the
      transverse relaxation rate R2*, as an estimate of iron content in seven brain
      regions. We found that R2* in globus pallidus was associated with WMH volume
      after adjusting for sociodemographic variables (partial correlation coefficient =
      0.521, P < 0.001) and in a multivariate analysis adjusted for common vascular
      risk factors (partial correlation coefficient = 0.572, P = 0.033). Regional R2*
      in globus pallidus was also significantly higher in WMHs than in controls (P =
      0.042). Iron content in globus pallidus, as assessed by R2* relaxometry, is
      independently linked to the severity of WMHs in our cohort of patients,
      suggesting that iron deposition in the brain may play a role in the pathogenesis
      of WMHs. This may provide prognostic information on patients with WMHs and may
      have implications for therapeutic interventions in WMHs.

PMID- 23129025
TI  - A novel B cell population revealed by a CD38/CD24 gating strategy: CD38(-)CD24 (
      ) B cells in centenarian offspring and elderly people.
AB  - The B cell arm of adaptive immunity undergoes significant modifications with age.
      Elderly people are characterized by impaired B cell responses reflected in a
      reduced ability to effectively respond against viruses and bacteria. Alterations
      of immunity with advancing age (immunosenescence) have been widely studied in
      centenarians who are considered a good example of successful aging. In recent
      years, attention has shifted to centenarian offspring (CO) as a model of people
      genetically advantaged for healthy aging and longevity. Here, we describe the
      preliminary characterization of a proposed new population of memory B cells,
      defined as CD19(+)CD38(-)CD24(-), which we find at higher frequencies in the
      elderly but less so in CO than healthy age-matched random controls. In addition,
      we found a decreased expression of RP105 (CD180), a toll-like receptor-associated
      molecule, on these cells. CD180 downregulation may potentially be a marker of
      immunosenescence. Moreover, we show that these CD19(+)CD38(-)CD24(-) B cells
      produce TNF and hypothesize that their observed expansion in the elderly might
      contribute to the increased inflammatory status sometimes designated "inflamm
      aging." 

PMID- 23129026
TI  - Dietary resveratrol prevents Alzheimer's markers and increases life span in
      SAMP8.
AB  - Resveratrol is a polyphenol that is mainly found in grapes and red wine and has
      been reported to be a caloric restriction (CR) mimetic driven by Sirtuin 1
      (SIRT1) activation. Resveratrol increases metabolic rate, insulin sensitivity,
      mitochondrial biogenesis and physical endurance, and reduces fat accumulation in
      mice. In addition, resveratrol may be a powerful agent to prevent age-associated
      neurodegeneration and to improve cognitive deficits in Alzheimer's disease (AD).
      Moreover, different findings support the view that longevity in mice could be
      promoted by CR. In this study, we examined the role of dietary resveratrol in
      SAMP8 mice, a model of age-related AD. We found that resveratrol supplements
      increased mean life expectancy and maximal life span in SAMP8 and in their
      control, the related strain SAMR1. In addition, we examined the resveratrol
      mediated neuroprotective effects on several specific hallmarks of AD. We found
      that long-term dietary resveratrol activates AMPK pathways and pro-survival
      routes such as SIRT1 in vivo. It also reduces cognitive impairment and has a
      neuroprotective role, decreasing the amyloid burden and reducing tau
      hyperphosphorylation. 

PMID- 23129028
TI  - Analysis of the efficacy of direct hemoperfusion with polymyxin B-immobilized
      fiber (PMX-DHP) according to the prognostic factors in patients with colorectal
      perforation.
AB  - PURPOSE: Direct hemoperfusion with polymyxin B-immobilized fiber (PMX-DHP) has
      been reported to improve the outcomes in patients with colorectal perforation. We
      retrospectively identified prognostic factors in patients with colorectal
      perforation and considered the efficacy of PMX-DHP based on these prognostic
      factors. METHODS: One hundred and fifty-six patients who underwent surgery for
      colorectal perforation in our department between November 1995 and March 2011
      were enrolled in this study. The clinicopathological factors were compared
      between the survivor and non-survivor groups. RESULTS: There were 28 patients
      (17.9 %) who died within 28 days after surgery. According to the multivariate
      analysis, an Acute Physiology and Chronic Health Evaluation II (APACHE II) score
      of 17 or more was a significant independent prognostic factor (P = 0.002, odds
      ratio = 5.39). There was a significant difference in the survival rates between
      the patients with APACHE II scores of 16 or less and those with scores of 17 or
      more who had received the PMX-DHP (+) (P < 0.0001). CONCLUSION: The APACHE II
      score is useful as a prognostic factor in patients with colorectal perforation,
      and the survival rate was 50 % or lower among the patients with APACHE II scores
      of 17 or higher. Therefore, PMX-DHP appears to have limited efficacy in serious
      cases.

PMID- 23129027
TI  - MicroRNAs in cancer diagnosis and therapy: from bench to bedside.
AB  - Epigenetic changes, such as DNA methylation and histone modifications, regulate
      gene expression. It is speculated that investigating the fundamental epigenetic
      mechanisms and their gene regulation will promote a better understanding of
      cancer development. The idea of epigenetic modification has been extended to
      microRNAs (miRs). MiRs are single-stranded RNA molecules, about 19-25
      ribonucleotides in length, which regulate gene expression post-transcriptionally
      and can act as tumor suppressors or oncogenes. We review the most recent findings
      related to their mechanisms of action, the modification of miR expression, and
      their relationship to cancer. We also discuss the potential application of miRs
      in the clinical setting, such as for biomarkers and therapy.

PMID- 23129030
TI  - When and how to die.

PMID- 23129029
TI  - MRI findings of lumbosacral metastasis from occult follicular thyroid cancer:
      report of a case.
AB  - A 63-year-old female was admitted to our hospital with bowel and bladder
      incontinence. Magnetic resonance imaging (MRI) showed a 13 * 12 * 12 cm mass
      invading the posterior regions of the L4, L5, S1 and S2 vertebrae with broad
      paravertebral soft tissue invasion. A Tru-cut biopsy of the mass was performed.
      The histopathological examination revealed metastatic follicular carcinoma of the
      thyroid. Thyroid functional tests were within the normal limits. Thyroid
      sonography revealed a heterogeneous, ill-defined, 14 * 9 mm hypoechoic solid
      nodule in the right lobe of the thyroid gland. On thyroid scintigraphy, an area
      of focal hyperactivity was detected in the right lobe at the nodule localization.
      Total thyroidectomy was performed, and the primary tumor pathology was determined
      to be follicular thyroid cancer. To our knowledge, only a few cases of
      lumbosacral cord compression as the initial manifestation of follicular thyroid
      carcinoma have been reported in the literature. We aimed to discuss the MRI
      findings of tumors in this age group with lumbosacral localization. 

PMID- 23129031
TI  - When and how to die.

PMID- 23129032
TI  - When and how to die.

PMID- 23129033
TI  - When and how to die.

PMID- 23129034
TI  - Are doctors all-powerful?

PMID- 23129035
TI  - Treatment of chronic wounds.
AB  - Treatment of underlying diseases is of paramount importance due to the complex
      genesis of chronic wounds. This should be followed by a stage-adapted wound
      treatment, which usually consists of a phase-adapted wound debridement, ensued by
      a moist wound treatment. In case of epithelialization, a phase-specific shift to
      dry wound treatment should be performed. Despite the growing number of new wound
      dressings and therapeutics, current scientific data is incomplete, and evidence
      for the effectiveness of these wound dressings is only sparse. No significant
      advantage of one wound dressing over the other exists. The status of negative
      pressure treatment is still controversial, and no clear evidence is present. In
      order to achieve a permanent treatment success, causal therapy of venous
      obstructions and/or arterial disorders is of importance. Systematic and
      consistent compression therapy is of utmost significance when treating venous
      wounds.

PMID- 23129036
TI  - Drug-eluting stents and perioperative risk - more than matters of the heart?
AB  - The introduction of drug-eluting stents (DES) to interventional cardiology has
      been a breakthrough in the treatment of in-stent restenosis. However, the
      downside of reduced restenosis is a significantly prolonged and practically
      incalculable time to reendothelialization of thrombogenic stent-surfaces with an
      increased risk for coronary thrombosis. As the use of DES in non-coronary
      arteries (e.g. carotid, renal, infrainguinal and even cerebral arteries) is
      increasing, new vascular beds might be put at risk of ischemia. The practice of
      stopping antiplatelet drugs in a perioperative setting is highly problematic and
      contemporary guidelines released by scientific societies from different medical
      specialties have recently addressed this problem. While many case reports have
      reported alarming incidents of stent thrombosis, prospective clinical data are
      scarcely available to guide anticoagulation during the perioperative phase. This
      review summarizes information on the vascular biology of DES and associated
      adverse events based on a systematic search of the available literature in public
      data bases. An emphasis is put on the growing use of DES in non-coronary vessels
      and the associated danger of putting new vascular beds at risk of thrombotic
      complications.

PMID- 23129037
TI  - The relationship between vitamin D deficiency and thoracic aortic dilatation.
AB  - BACKGROUND: Vitamin D deficiency can play a role in cardiovascular conditions,
      such as coronary artery disease, heart failure and hypertension. Vitamin D
      deficiency can activate the renin-angiotensin-aldosterone system, which in turn
      affects the cardiovascular system. Thus, a relationship between vitamin D
      deficiency and thoracic aortic dilatation (TAD) and aneurysm could be postulated.
      In this study, we compared 25-OH vitamin D levels between TAD and control groups.
      PATIENTS AND METHODS: This study included 87 patients with TAD who were 40 - 70
      years old. The control group consisted of 93 patients who were 40 - 70 years old
      and did not have TAD. A transthoracic echocardiography was performed on each
      patient. Along with routine tests, the 25-OH vitamin D and parathormone (PTH)
      levels were analyzed. RESULTS: No statistically significant difference was found
      between the two groups regarding their basic characteristics. The average PTH
      level of the TAD group was higher than that of the control group (94.87 +/- 44.96
      and 66.39 +/- 30.58 pg/ml, respectively; p < 0.001). The average 25-OH vitamin D
      level of the TAD group was lower than that of the control group (11.89 +/- 7.54
      and 15.98 +/- 4.98 ng/ml, respectively; p = 0.001). The initial conventional
      echocardiographic parameters of both groups were comparable. Logistic regression
      analysis revealed that the PTH and 25-OH vitamin D levels were independent
      predictors of TAD. CONCLUSIONS: Vitamin D deficiency was found as an independent
      factor associated with TAD.

PMID- 23129038
TI  - Stenting of stenotic mesenteric arteries for symptomatic chronic mesenteric
      ischemia.
AB  - BACKGROUND: We report the results of our single center series of patients with
      chronic mesenteric ischemia (CMI) to determine the role of stenting in the
      management of patients. PATIENTS AND METHODS: We retrospectively reviewed all
      patients with CMI treated endovascularly with stent revascularisation from
      January 2008 to January 2011.CMI diagnosis was made according to clinical
      symptoms, including postprandial abdominal pain, food fear, and weight loss.
      Additionally, the diagnosis was confirmed by duplex ultrasonography and/or
      computed tomography angiography and/or contrast-enhanced magnetic resonance
      angiography. RESULTS: All 45 patients presented with typical CMI symptoms: 45/45
      (100 %) had postprandial pain, 31/45 (68.8 %) had a weight loss of more than 10
      kilograms, and 11/45 (24.4 %) suffered from ischemic colitis combined with lower
      gastrointestinal bleeding. In three patients occlusion could not be crossed,
      therefore considered as technical failure. A total of 55 arteries were stented in
      the remaining 42 patients. Nineteen patients underwent SMA stenting alone, eight
      underwent celiac stenting, alone and three patients underwent stenting of
      inferior mesenteric artery (IMA) alone. We performed combined stenting of the
      celiac artery and superior mesenteric artery in ten patients, and one patient
      underwent a combined stenting of the celiac artery and the IMA. All three
      mesenteric arteries were stented in only one patient. Primary technical success
      was achieved in 42/45 (94.8 %) patients. Clinical symptom relief was achieved in
      39/45 (86.6 %) patients with abdominal pain. Increased body weight was observed
      in 28/31 (90.3 %) patients with an average weight gain of 8.8 kilograms (5 - 12
      kilograms), and 10/11 (90.9 %) patients recovered from ischaemic colitis/lower
      gastrointestinal bleeding. CONCLUSIONS: Stent revascularisation can be considered
      as the first-line therapy for patients with chronic mesenteric ischemia.

PMID- 23129039
TI  - Differences in patterns of peripheral arterial occlusive disease and eligibility
      for endovascular treatment.
AB  - BACKGROUND: To analyze differences in morphological changes in the vascular tree
      among patients presenting with intermittent claudication (IC) and critical limb
      ischemia (CLI). In addition, suitability for endovascular treatment was
      evaluated. PATIENTS AND METHODS: Our study included 690 lower extremities with IC
      or CLI in 500 consecutive patients who were assessed by magnetic resonance
      angiography (MRA) according to the TASC II classification and in terms of the
      below the knee run-off status. Multivariable logistic regressions models adjusted
      for cardiovascular risk factors were used to evaluate differences in
      arteriosclerotic lesion patterns and eligibility for endovascular treatment.
      RESULTS: Multivariable analysis showed that compared with IC extremities, CLI
      extremities have significantly more severe arteriosclerotic lesions at the
      aortoiliac (p < 0.001), femoropopliteal (p < 0.001), and crural levels (p <
      0.001), with a greater risk of multilevel disease (odds ratio [OR], 1.71; 95 %
      confidence interval [CI] 1.10 - 2.66; p = 0.018). More than 80 % of extremities
      with IC and more than 50 % of extremities with CLI appeared to be eligible for
      endovascular treatment in an isolated evaluation of the aortoiliac and
      femoropopliteal axis. For combined evaluation of the aortoiliac and
      femoropopliteal axis, the proportion of endovascular suitability (TASC A+B
      lesions) decreased to 65 % (IC) and 41 % (CLI). For TASC A+B+C lesions, the
      proportions were 79 % (IC) and 41 % (CLI). CONCLUSIONS: Lower extremities with IC
      and CLI significantly differ in terms of arteriosclerotic lesion morphology and
      patterns of lesion localization. The majority of IC and CLI extremities appear to
      be eligible for endovascular treatment. Because of further improvement in
      endovascular equipment, even more patients will be eligible for treatment.

PMID- 23129040
TI  - Determinants of intermediate term clinical outcome after endovascular below-knee
      interventions.
AB  - BACKGROUND: To determine predictors of clinical outcome after endovascular
      interventions of crural arteries in patients with peripheral arterial disease.
      PATIENTS AND METHODS: We prospectively followed 154 limbs in 147 patients treated
      with below the knee endovascular interventions for critical limb ischemia (52 %)
      and severe claudication (48 %). Patient-immanent, hemodynamic-procedural and
      anatomic determinants of outcome were analyzed. Outcome was defined as event-free
      survival from the combined endpoint freedom from re-intervention, major
      amputation and death. RESULTS: Cumulative event-free survival after 12 months was
      65.1 %. During follow-up 42 patients (27.3 %) required re-intervention, 8 (5.2 %)
      underwent major amputation and 5 (3.2 %) died. In univariate analyses, the
      presence of critical limb ischemia, multilevel disease, age > 72 years, impaired
      renal function, and long lesions (> 65 mm) were significant determinants of the
      study endpoint. The anatomic location of the lesion, distal patency of treated
      artery below the ankle, cardiovascular risk factors or concomitant cardiovascular
      diseases, and the type of postinterventional antithrombotic treatment did not
      influence outcome. CONCLUSIONS: Below-knee interventions resulted in acceptable
      procedural mid-term results and high rates of amputation free survival.
      Multilevel disease, long lesions and impaired renal function were indicative of a
      worse outcome.

PMID- 23129041
TI  - Combined immunosuppressive therapy including a TNF-alpha blocker induces
      remission in a difficult to treat patient with Takayasu arteriitis and coronary
      involvement.
AB  - A 40 year old woman presented with symptoms of a systemic inflammatory disease
      and obstruction of the left subclavian artery. Takayasu arteriitis (TA) was
      clinically diagnosed and confirmed by MR angiography and FDG-PET scan showing
      inflammation of the aortic arch and the left subclavian artery. Immunosuppression
      with glucocorticoids and methotrexate resulted in immediate clinical improvement
      and normalization of systemic markers of inflammation. Despite that the patient
      developed chest pain on exertion suggesting coronary involvement, which was
      confirmed by dobutamine stress echocardiography. After adding the TNF-alpha
      blocker infliximab coronary symptoms gradually improved and a clinically stable
      situation could be achieved for more than 6 months. Coronary angiography and
      aortography showed an occluded main stem of the left coronary artery, an occluded
      left subclavian artery, and stenoses of the brachiocephalic trunk and the left
      common carotid artery. Revascularization of the coronary artery and the aortic
      arch and its branches was performed. The patient returned to work two months
      after the operation. Immunosuppressive therapy with infliximab and methotrexate
      is continued, glucocorticoids were stopped after one year of treatment. This case
      shows that vascular progress in TA patients may occur even when systemic
      inflammation is controlled, therefore patients have to be carefully observed for
      new vascular manifestations. TNF-alpha blockers may be an additional treatment
      option in otherwise difficult to treat TA patients allowing to perform
      revascularization after a stable disease state has been achieved.

PMID- 23129042
TI  - Crush implantation of a self-expanding interwoven stent over a subintimally
      recanalized standard stent in a TASC D lesion of the superficial femoral artery.
AB  - We demonstrate feasibility of implantation of a self-expanding interwoven nitinol
      stent in a claudicant, where recanalization attempt of a heavily calcified,
      occluded superficial femoral artery (TASC D lesion) was complicated by a
      previously implanted, fractured standard stent. Wire passage through the
      occlusion and beyond the fractured stent could only be achieved through the
      subintimal space. A dedicated reentry device was used to allow distal wire entry
      into the true lumen at the level of the popliteal artery. Despite crushing of the
      fractured stent with a series of increasingly sized standard balloons, a
      significant recoil remainded in the area of the crushed stent. To secure patency
      of the femoro-popliteal artery we therefore decided to implant the novel self
      expanding interwoven nitinol stent (Supera Veritas (TM), IDEV), whose unique
      feature is an exceptional high radial strength. Patient presented asymptomatic
      without any impairment of his walking capacity at three month follow up and
      duplex ultrasound confirmed patency of the stent. Subintimal recanalizations can
      be complicated by previously implanted stents, in particular in the presence of
      stent fracture, where intraluminal wire passage often can not be achieved.
      Considering the high radial strength and fracture resistance, interwoven nitinol
      stents represent a good treatment option in those challenging cases and they can
      be used to crush standard nitinol and ballonexpandable stents.

PMID- 23129043
TI  - [Curriculum for interventional therapy for arterial diseases. Clinical competence
      for execution of catheter-based interventions on the arteries of the extremities,
      on the pelvic, visceral and renal arteries, on the extracranial arteries
      supplying the brain, and on dialysis shunts].

PMID- 23129044
TI  - Clarifying the role of fire heat and daily temperature fluctuations as
      germination cues for Mediterranean Basin obligate seeders.
AB  - BACKGROUND AND AIMS: This study aims to determine the role that both direct
      effects of fire and subsequent daily temperature fluctuations play in the seed
      bank dynamics of obligate seeders from the Mediterranean Basin. The short yet
      high soil temperatures experienced due to passage of fire are conflated with the
      lower, but longer, temperatures experienced by daily fluctuations which occur
      after removing vegetation. These germination cues are able to break seed
      dormancy, but it is difficult to assess their specific level of influence because
      they occur consecutively after summer fires, just before the flush of germination
      in the wet season (autumn). METHODS: By applying experimental fires, seed
      treatments were imposed that combined fire exposure/non-fire exposure with
      exposure to microhabitats under a gradient of disturbance (i.e. gaps opened by
      fire, mechanical brushing and intact vegetation). The seeds used were
      representative of the main families of obligate seeders (Ulex parviflorus, Cistus
      albidus and Rosmarinus officinalis). Specifically, an assessment was made of (1)
      the proportion of seeds killed by fire, (2) seedling emergence under field
      conditions and (3) seeds which remained ungerminated in soil. KEY RESULTS: For
      the three species studied, the factors that most influenced seedling emergence
      and seeds remaining ungerminated were microhabitats with higher temperature
      fluctuations after fire (gaps opened by fire and brushing treatments). The direct
      effect of fire decreased the seedling emergence of U. parviflorus and reduced the
      proportion of seeds of R. officinalis remaining ungerminated. CONCLUSIONS: The
      relevance of depleting vegetation (and subsequent daily temperature fluctuation
      in summer) suggests that studies focusing on lower temperature thresholds for
      breaking seed dormancy are required. This fact also supports the hypothesis that
      the seeding capacity in Mediterranean Basin obligate seeders may have evolved as
      a response to a wide range of disturbances, and not exclusively to fire.

PMID- 23129045
TI  - Investigation of nanoscopic free volume and interfacial interaction in an epoxy
      resin/modified clay nanocomposite using positron annihilation spectroscopy.
AB  - Epoxy/clay nanocomposites are synthesized using clay modified with the organic
      modifier N,N-dimethyl benzyl hydrogenated tallow quaternary ammonium salt
      (Cloisite 10A). The purpose is to investigate the influence of the clay
      concentration on the nanostructure, mainly on the free-volume properties and the
      interfacial interactions, of the epoxy/clay nanocomposite. Nanocomposites having
      1, 3, 5 and 7.5 wt. % clay concentrations are prepared using the solvent-casting
      method. The dispersion of clay silicate layers and the morphologies of the
      fractured surfaces in the nanocomposites are studied using X-ray diffraction
      (XRD) and scanning electron microscopy (SEM), respectively. The observed XRD
      patterns reveal an exfoliated clay structure in the nanocomposite with the lowest
      clay concentration (<=1 wt. %). The ortho-positronium lifetime (tau(3)), a
      measure of the free-volume size, as well as the fractional free volume (f(v)) are
      seen to decrease in the nanocomposites as compared to pristine epoxy. The
      intensity of free positron annihilation (I(2)), an index of the epoxy-clay
      interaction, decreases with the addition of clay (1 wt. %) but increases linearly
      at higher clay concentrations. Positron age-momentum correlation measurements are
      also carried out to elucidate the positron/positronium states in pristine epoxy
      and in the nanocomposites. The results suggest that in the case of the
      nanocomposite with the studied lowest clay concentration (1 wt. %), free
      positrons are primarily localized in the epoxy-clay interfaces, whereas at higher
      clay concentrations, annihilation takes place from the intercalated clay layers.

PMID- 23129046
TI  - Prospective study of the Wilson severity-of-illness scoring system for
      complicated skin and skin structure infections.
AB  - Wilson et al. (Am. J. Surg. 185:369-375, 2003) developed a disease severity
      classification system for use in complicated skin and skin structure infections
      (cSSSI). Two phase 3 trials of ceftaroline fosamil in cSSSI provided the
      opportunity to evaluate the association between Wilson Severity Risk Class and
      clinical cure rates. Our analyses did not confirm that an association exists
      between Wilson Severity Risk Class and clinical cure rate and, thus, did not
      validate its predictive utility.

PMID- 23129047
TI  - 4(1H)-Quinolones with liver stage activity against Plasmodium berghei.
AB  - With the exception of primaquine, tafenoquine, and atovaquone, there are very few
      antimalarials that target liver stage parasites. In this study, a transgenic
      Plasmodium berghei parasite (1052Cl1; PbGFP-Luc(con)) that expresses luciferase
      was used to assess the anti-liver stage parasite activity of ICI 56,780, a 7-(2
      phenoxyethoxy)-4(1H)-quinolone (PEQ), as well as two 3-phenyl-4(1H)-quinolones
      (P4Q), P4Q-146 and P4Q-158, by using bioluminescent imaging (BLI). Results showed
      that all of the compounds were active against liver stage parasites; however, ICI
      56,780 and P4Q-158 were the most active, with low nanomolar activity in vitro and
      causal prophylactic activity in vivo. This potent activity makes these compounds
      ideal candidates for advancement as novel antimalarials.

PMID- 23129048
TI  - Genotypic and phenotypic analyses of hepatitis C virus from patients treated with
      JTK-853 in a three-day monotherapy.
AB  - JTK-853, a palm site-binding NS5B nonnucleoside polymerase inhibitor, shows
      antiviral activity in vitro and in hepatitis C virus (HCV)-infected patients.
      Here, we report the results of genotypic and phenotypic analyses of resistant
      variants in 24 HCV genotype 1-infected patients who received JTK-853 (800, 1,200,
      or 1,600 mg twice daily or 1,200 mg three times daily) in a 3-day monotherapy.
      Viral resistance in NS5B was investigated using HCV RNA isolated from serum
      specimens from the patients. At the end of treatment (EOT) with JTK-853, the
      amino acid substitutions M414T (methionine [M] in position 414 at baseline was
      replaced with threonine [T] at EOT), C445R (cysteine [C] in position 445 at
      baseline was replaced with arginine [R] at EOT), Y448C/H (tyrosine [Y] in
      position 448 at baseline was replaced with cysteine [C] or histidine [H] at EOT),
      and L466F (leucine [L] in position 466 at baseline was replaced with
      phenylalanine [F] at EOT), which are known to be typical resistant variants of
      nonnucleoside polymerase inhibitors, were observed in a clonal sequencing
      analysis. These substitutions were also selected by a treatment with JTK-853 in
      vitro, and the 50% effective concentration of JTK-853 in the M414T-, C445F-,
      Y448H-, and L466V-harboring replicons attenuated the susceptibility by 44-, 5-, 6
      , and 21-fold, respectively, compared with that in the wild-type replicon (Con1).
      These findings suggest that amino acid substitutions of M414T, C445R, Y448C/H,
      and L466F are thought to be viral resistance mutations in HCV-infected patients
      receiving JTK-853 in a 3-day monotherapy.

PMID- 23129049
TI  - The therapeutic effect of tigecycline, unlike that of Ceftazidime, is not
      influenced by whether the Klebsiella pneumoniae strain produces extended-spectrum
      beta-lactamases in experimental pneumonia in rats.
AB  - The efficacies of tigecycline and ceftazidime against fatal pneumonia in rats
      caused by an extended-spectrum beta-lactamase (ESBL)-positive Klebsiella
      pneumoniae strain or its wild-type (WT) progenitor were compared. Ceftazidime at
      12.5 or 50 mg/kg of body weight twice daily (b.i.d.) was effective (50% or 100%
      rat survival) in pneumonia caused by the WT isolate but unsuccessful (100% rat
      mortality) in pneumonia caused by the ESBL-positive variant. In contrast,
      tigecycline at 6.25, 12.5, or 25 mg/kg b.i.d. showed dosage-dependent efficacy up
      to 100% rat survival irrespective of the ESBL character of the infecting
      organism.

PMID- 23129050
TI  - Novel aminoglycoside 2''-phosphotransferase identified in a gram-negative
      pathogen.
AB  - Aminoglycoside 2"-phosphotransferases are the major aminoglycoside-modifying
      enzymes in clinical isolates of enterococci and staphylococci. We describe a
      novel aminoglycoside 2"-phosphotransferase from the Gram-negative pathogen
      Campylobacter jejuni, which shares 78% amino acid sequence identity with the
      APH(2")-Ia domain of the bifunctional aminoglycoside-modifying enzyme
      aminoglycoside (6') acetyltransferase-Ie/aminoglycoside 2"-phosphotransferase-Ia
      or AAC(6')-Ie/APH(2")-Ia from Gram-positive cocci, which we called APH(2")-If.
      This enzyme confers resistance to the 4,6-disubstituted aminoglycosides
      kanamycin, tobramycin, dibekacin, gentamicin, and sisomicin, but not to
      arbekacin, amikacin, isepamicin, or netilmicin, but not to any of the 4,5
      disubstituted antibiotics tested. Steady-state kinetic studies demonstrated that
      GTP, and not ATP, is the preferred cosubstrate for APH(2")-If. The enzyme
      phosphorylates the majority of 4,6-disubstituted aminoglycosides with high
      catalytic efficiencies (k(cat)/K(m) = 10(5) to 10(7) M(-1) s(-1)), while the
      catalytic efficiencies against the 4,6-disubstituted antibiotics amikacin and
      isepamicin are 1 to 2 orders of magnitude lower, due mainly to the low apparent
      affinities of these substrates for the enzyme. Both 4,5-disubstituted antibiotics
      and the atypical aminoglycoside neamine are not substrates of APH(2")-If, but are
      inhibitors. The antibiotic susceptibility and substrate profiles of APH(2")-If
      are very similar to those of the APH(2")-Ia phosphotransferase domain of the
      bifunctional AAC(6')-Ie/APH(2")-Ia enzyme.

PMID- 23129051
TI  - Antimicrobial photodynamic inactivation inhibits Candida albicans virulence
      factors and reduces in vivo pathogenicity.
AB  - The objective of this study was to evaluate whether Candida albicans exhibits
      altered pathogenicity characteristics following sublethal antimicrobial
      photodynamic inactivation (APDI) and if such alterations are maintained in the
      daughter cells. C. albicans was exposed to sublethal APDI by using methylene blue
      (MB) as a photosensitizer (0.05 mM) combined with a GaAlAs diode laser (lambda
      660 nm, 75 mW/cm(2), 9 to 27 J/cm(2)). In vitro, we evaluated APDI effects on C.
      albicans growth, germ tube formation, sensitivity to oxidative and osmotic
      stress, cell wall integrity, and fluconazole susceptibility. In vivo, we
      evaluated C. albicans pathogenicity with a mouse model of systemic infection.
      Animal survival was evaluated daily. Sublethal MB-mediated APDI reduced the
      growth rate and the ability of C. albicans to form germ tubes compared to
      untreated cells (P < 0.05). Survival of mice systemically infected with C.
      albicans pretreated with APDI was significantly increased compared to mice
      infected with untreated yeast (P < 0.05). APDI increased C. albicans sensitivity
      to sodium dodecyl sulfate, caffeine, and hydrogen peroxide. The MIC for
      fluconazole for C. albicans was also reduced following sublethal MB-mediated
      APDI. However, none of those pathogenic parameters was altered in daughter cells
      of C. albicans submitted to APDI. These data suggest that APDI may inhibit
      virulence factors and reduce in vivo pathogenicity of C. albicans. The absence of
      alterations in daughter cells indicates that APDI effects are transitory. The MIC
      reduction for fluconazole following APDI suggests that this antifungal could be
      combined with APDI to treat C. albicans infections.

PMID- 23129052
TI  - Population pharmacokinetic-pharmacodynamic analysis of anidulafungin in adult
      patients with fungal infections.
AB  - To evaluate the exposure-response relationships for efficacy and safety of
      intravenous anidulafungin in adult patients with fungal infections, a population
      pharmacokinetic-pharmacodynamic (PK-PD) analysis was performed with data from 262
      patients in four phase 2/3 studies. The plasma concentration data were fitted
      with a previously developed population PK model. Anidulafungin exposures in
      patients with weight extremities (e.g., 40 kg and 150 kg) were simulated based on
      the final PK model. Since the patient population, disease status, and efficacy
      endpoints varied in these studies, the exposure-efficacy relationship was
      investigated separately for each study using logistic regression as appropriate.
      Safety data from three studies (n = 235) were pooled for analysis, and one study
      was excluded due to concomitant use of amphotericin B as a study treatment and
      different disease populations. The analysis showed that the same dosing regimen
      of anidulafungin can be administered to all patients regardless of body weight.
      Nonetheless, caution should be taken for patients with extremely high weight
      (e.g., >150 kg). There was a trend of positive association between anidulafungin
      exposure and efficacy in patients with esophageal candidiasis or invasive
      candidiasis, including candidemia (ICC); however, adequate characterization of
      the effect of anidulafungin exposure on response could not be established due to
      the relatively small sample size. No threshold value for exposure could be
      established, since patients with low exposure also achieved successful outcomes
      (e.g., area under the curve < 40 mg . h/liter in ICC patients). There was no
      association between anidulafungin exposure and the treatment-related adverse
      events or all-causality hepatic laboratory abnormalities.

PMID- 23129053
TI  - Targeting organic anion transporter 3 with probenecid as a novel anti-influenza a
      virus strategy.
AB  - Influenza A virus infection is a major global health concern causing significant
      mortality, morbidity, and economic loss. Antiviral chemotherapeutics that target
      influenza A virus are available; however, rapid emergence of drug-resistant
      strains has been reported. Consequently, there is a burgeoning need to identify
      novel anti-influenza A drugs, particularly those that target host gene products
      required for virus replication, to reduce the likelihood of drug resistance. In
      this study, a small interfering RNA (siRNA) screen was performed to identify host
      druggable gene targets for anti-influenza A virus therapy. The host organic anion
      transporter-3 gene (OAT3), a member of the SLC22 family of transporters, was
      validated as being required to support influenza A virus replication. Probenecid,
      a prototypical uricosuric agent and chemical inhibitor of organic anion
      transporters known to target OAT3, was shown to be effective in limiting
      influenza A virus infection in vitro (50% inhibitory concentration [IC(50)] of
      5.0 * 10(-5) to 5.0 * 10(-4) MUM; P < 0.005) and in vivo (P < 0.05). Probenecid
      is widely used for treatment of gout and related hyperuricemic disorders, has
      been extensively studied for pharmacokinetics and safety, and represents an
      excellent candidate for drug repositioning as a novel anti-influenza A
      chemotherapeutic.

PMID- 23129054
TI  - A class of tricyclic compounds blocking malaria parasite oocyst development and
      transmission.
AB  - Malaria is a deadly infectious disease in many tropical and subtropical
      countries. Previous efforts to eradicate malaria have failed, largely due to the
      emergence of drug-resistant parasites, insecticide-resistant mosquitoes and, in
      particular, the lack of drugs or vaccines to block parasite transmission. ATP
      binding cassette (ABC) transporters are known to play a role in drug transport,
      metabolism, and resistance in many organisms, including malaria parasites. To
      investigate whether a Plasmodium falciparum ABC transporter (Pf14_0244 or
      PfABCG2) modulates parasite susceptibility to chemical compounds or plays a role
      in drug resistance, we disrupted the gene encoding PfABCG2, screened the
      recombinant and the wild-type 3D7 parasites against a library containing 2,816
      drugs approved for human or animal use, and identified an antihistamine
      (ketotifen) that became less active against the PfABCG2-disrupted parasite in
      culture. In addition to some activity against asexual stages and gametocytes,
      ketotifen was highly potent in blocking oocyst development of P. falciparum and
      the rodent parasite Plasmodium yoelii in mosquitoes. Tests of structurally
      related tricyclic compounds identified additional compounds with similar
      activities in inhibiting transmission. Additionally, ketotifen appeared to have
      some activity against relapse of Plasmodium cynomolgi infection in rhesus
      monkeys. Further clinical evaluation of ketotifen and related compounds,
      including synthetic new derivatives, in blocking malaria transmission may provide
      new weapons for the current effort of malaria eradication.

PMID- 23129055
TI  - Evaluation of an expanded microarray for detecting antibiotic resistance genes in
      a broad range of gram-negative bacterial pathogens.
AB  - A microarray capable of detecting genes for resistance to 75 clinically relevant
      antibiotics encompassing 19 different antimicrobial classes was tested on 132
      Gram-negative bacteria. Microarray-positive results correlated >91% with
      antimicrobial resistance phenotypes, assessed using British Society for
      Antimicrobial Chemotherapy clinical breakpoints; the overall test specificity was
      >83%. Microarray-positive results without a corresponding resistance phenotype
      matched 94% with PCR results, indicating accurate detection of genes present in
      the respective bacteria by microarray when expression was low or absent and,
      hence, undetectable by susceptibility testing. The low sensitivity and negative
      predictive values of the microarray results for identifying resistance to some
      antimicrobial resistance classes are likely due to the limited number of
      resistance genes present on the current microarray for those antimicrobial agents
      or to mutation-based resistance mechanisms. With regular updates, this microarray
      can be used for clinical diagnostics to help accurate therapeutic options to be
      taken following infection with multiple-antibiotic-resistant Gram-negative
      bacteria and prevent treatment failure.

PMID- 23129056
TI  - The effect of a single session of short duration heart rate variability
      biofeedback on EEG: a pilot study.
AB  - This pilot study examines the effect of heart rate variability (HRV) biofeedback
      on measures of electroencephalogram (EEG) during and immediately after
      biofeedback. Eighteen healthy males exposed to work-related stress, were
      randomised into an HRV biofeedback (BIO) or a comparative group (COM). EEG was
      recorded during the intervention and during rest periods before and after the
      intervention. Power spectral density in theta, alpha and beta frequency bands and
      theta/beta ratios were calculated. During the intervention, the BIO group had
      higher relative theta power [Fz and Pz (p < 0.01), Cz (p < 0.05)], lower fronto
      central relative beta power (p < 0.05), and higher theta/beta [Fz and Cz (p <
      0.01), Pz (p < 0.05)] than the COM group. The groups showed different responses
      after the intervention with increased posterior theta/beta (p < 0.05) in the BIO
      group and altered posterior relative theta (p < 0.05), central relative beta (p =
      0.06) and central-posterior theta/beta (p < 0.01) in the post-intervention rest
      period. The findings of this study suggest that a single session of HRV
      biofeedback after a single training session was associated with changes in EEG
      suggestive of increased internal attention and relaxation both during and after
      the intervention. However, the comparative intervention was associated with
      changes suggestive of increased mental effort and possible anxiety during and
      after the intervention.

PMID- 23129057
TI  - Growth inhibition of Tax-activated human Jurkat leukemia T cells by all-trans
      retinoic acid requires JNK-1 inhibition.
AB  - Retinoids, including vitamin A (retinol) and its analogues, are critical for a
      variety of biological functions. In this study, we report that all-trans retinoic
      acid (ATRA) decreases Jun N-terminal kinase 1 (JNK-1) activity, antagonizing the
      effect of the Tax protein in Jurkat leukemia T cells transiently transfected for
      expressing the Tax protein. The Tax protein is one of the products of the human T
      cell leukemia virus type 1 (HTLV-1) which is the etiologic agent of adult T-cell
      leukemia (ATL), an aggressive neoplasia of CD4+ T cells. The decrease in JNK-1
      activity was followed by a marked decrease in the expression of interleukin (IL)
      2 and a weak increase in interferon (IFN)-gamma in Jurkat cells treated with ATRA
      in a dose-dependent manner, suggesting a correlation between the expression of
      JNK-1 and the activity of the Tax protein. However, the expression levels of IL-4
      and IL-10 were enhanced in cells transfected with Tax, compared with the levels
      in untransfected cells, but the expression levels were not affected following
      ATRA treatment. In transfection studies using a luciferase reporter construct
      expressing the IL-2 promoter or a tandem repeat of AP-1 or NF-kappaB, the
      inhibitory effect of ATRA on the IL-2 promoter and AP-1 construct was confirmed
      at the transcriptional level. However, the inhibitory effect in the NF-kappaB
      reporter construct was only marginal. In addition, our data demonstrated that JNK
      1 is constitutively activated in Jurkat leukemia T cells expressing the Tax
      protein, suggesting that JNK-1 is required for Tax-induced proliferation of
      Jurkat leukemia cells.

PMID- 23129058
TI  - Protective effects of hydrogen sulfide on oxidative stress and fibrosis in
      hepatic stellate cells.
AB  - In hepatic fibrosis, hepatic stellate cells (HSCs) are activated and change into
      myofibroblast-like cells which are characterized by increased proliferation and
      extracellular matrix (ECM) synthesis. In this study, we investigated the
      regulatory effects of hydrogen sulfide (H2S) on hepatic fibrosis. We detected the
      proliferation, cell cycle progression, apoptosis, intracellular reactive oxygen
      species (ROS) and free calcium levels in ferric nitrilotriacetate (Fe-NTA)
      activated HSCs treated with sodium hydrogen sulphide (NaHS), an H2S-releasing
      molecule. We also evaluated the effects of NaHS on fibrosis and ECM synthesis in
      rats with hepatic fibrosis induced by carbon tetrachloride (CCl4). MTT assay
      revealed that NaHS (500 umol/l) suppressed the Fe-NTA-induced proliferation of
      HSC-T6 cells in a dose-dependent manner. NaHS induced G1 phase cell cycle arrest
      and apoptosis in the Fe-NTA-treated HSC-T6 cells. Furthermore, in the Fe-NTA
      treated HSC-T6 cells, NaHS reduced intracellular levels of ROS at 1, 3 and 6 h
      and reduced intracellular free calcium levels at 3 and 6 h. H2S administration
      attenuated hepatic fibrosis and collagen I protein expression in the rats with
      CCl4-induced hepatic fibrosis. In conclusion, exogenous H2S inhibits
      proliferation and induces cell cycle arrest and apoptosis in activated HSCs and
      attenuates CCl4-induced hepatic fibrosis and ECM expression. 

PMID- 23129059
TI  - Peace and war: trajectories of posttraumatic stress disorder symptoms before,
      during, and after military deployment in Afghanistan.
AB  - In the study reported here, we examined posttraumatic stress disorder (PTSD)
      symptoms in 746 Danish soldiers measured on five occasions before, during, and
      after deployment to Afghanistan. Using latent class growth analysis, we
      identified six trajectories of change in PTSD symptoms. Two resilient
      trajectories had low levels across all five times, and a new-onset trajectory
      started low and showed a marked increase of PTSD symptoms. Three temporary
      benefit trajectories, not previously described in the literature, showed
      decreases in PTSD symptoms during (or immediately after) deployment, followed by
      increases after return from deployment. Predeployment emotional problems and
      predeployment traumas, especially childhood adversities, were predictors for
      inclusion in the nonresilient trajectories, whereas deployment-related stress was
      not. These findings challenge standard views of PTSD in two ways. First, they
      show that factors other than immediately preceding stressors are critical for
      PTSD development, with childhood adversities being central. Second, they
      demonstrate that the development of PTSD symptoms shows heterogeneity, which
      indicates the need for multiple measurements to understand PTSD and identify
      people in need of treatment.

PMID- 23129060
TI  - The faintest speck of dirt: disgust enhances the detection of impurity.
AB  - Purity is commonly regarded as being physically embodied in the color white, with
      even trivial deviations from whiteness indicating a loss of purity. In three
      studies, we explored the implications of this "white = pure" association for
      disgust, an emotion that motivates the detection and avoidance of impurities that
      threaten purity and cleanliness. We hypothesized that disgust tunes perception to
      prioritize the light end of the light-dark spectrum, which results in a relative
      hypersensitivity to changes in lightness in this range. In studies 1 and 2,
      greater sensitivity to disgusting stimuli was associated with greater ability to
      make subtle gray-scale discriminations (e.g., detecting a faint gray stimulus
      against a white background) at the light end of the spectrum relative to ability
      to make subtle gray-scale discriminations at the dark end of the spectrum. In
      study 3, after viewing disgusting images, disgust-sensitive individuals
      demonstrated a heightened ability to detect deviations from white. These findings
      suggest that disgust not only motivates people to avoid impurities, but actually
      makes them better able to see them.

PMID- 23129061
TI  - Optimal social-networking strategy is a function of socioeconomic conditions.
AB  - In the two studies reported here, we examined the relation among residential
      mobility, economic conditions, and optimal social-networking strategy. In study
      1, a computer simulation showed that regardless of economic conditions, having a
      broad social network with weak friendship ties is advantageous when friends are
      likely to move away. By contrast, having a small social network with deep
      friendship ties is advantageous when the economy is unstable but friends are not
      likely to move away. In study 2, we examined the validity of the computer
      simulation using a sample of American adults. Results were consistent with the
      simulation: American adults living in a zip code where people are residentially
      stable but economically challenged were happier if they had a narrow but deep
      social network, whereas in other socioeconomic conditions, people were generally
      happier if they had a broad but shallow networking strategy. Together, our
      studies demonstrate that the optimal social-networking strategy varies as a
      function of socioeconomic conditions.

PMID- 23129062
TI  - Detecting the trustworthiness of novel partners in economic exchange.
AB  - Because trusting strangers can entail high risk, an ability to infer a potential
      partner's trustworthiness would be highly advantageous. To date, however, little
      evidence indicates that humans are able to accurately assess the cooperative
      intentions of novel partners by using nonverbal signals. In two studies involving
      human-human and human-robot interactions, we found that accuracy in judging the
      trustworthiness of novel partners is heightened through exposure to nonverbal
      cues and identified a specific set of cues that are predictive of economic
      behavior. Employing the precision offered by robotics technology to model and
      control humanlike movements, we demonstrated not only that experimental
      manipulation of the identified cues directly affects perceptions of
      trustworthiness and subsequent exchange behavior, but also that the human mind
      will utilize such cues to ascribe social intentions to technological entities.

PMID- 23129063
TI  - Contaminants in stream sediments from seven United States metropolitan areas:
      part I: distribution in relation to urbanization.
AB  - Organic contaminants and trace elements were measured in bed sediments collected
      from streams in seven metropolitan study areas across the United States to assess
      concentrations in relation to urbanization. Polycyclic aromatic hydrocarbons,
      polychlorinated biphenyls, organochlorine pesticides, the pyrethroid insecticide
      bifenthrin, and several trace elements were significantly related to urbanization
      across study areas. Most contaminants (except bifenthrin, chromium, nickel) were
      significantly related to the total organic carbon (TOC) content of the sediments.
      Regression models explained 45-80 % of the variability in individual contaminant
      concentrations using degree of urbanization, sediment-TOC, and study-area
      indicator variables (which represent the combined influence of unknown factors,
      such as chemical use or release, that are not captured by available explanatory
      variables). The significance of one or more study-area indicator variables in all
      models indicates marked differences in contaminant levels among some study areas,
      even after accounting for the nationally modeled effects of urbanization and
      sediment-TOC. Mean probable effect concentration quotients (PECQs) were
      significantly related to urbanization. Trace elements were the major contributors
      to mean PECQs at undeveloped sites, whereas organic contaminants, especially
      bifenthrin, were the major contributors at highly urban sites. Pyrethroids, where
      detected, accounted for the largest share of the mean PECQ. Part 2 of this series
      (Kemble et al. 2012) evaluates sediment toxicity to amphipods and midge in
      relation to sediment chemistry.

PMID- 23129064
TI  - Contaminants in stream sediments from seven United States metropolitan areas:
      part II--sediment toxicity to the amphipod Hyalella azteca and the midge
      Chironomus dilutus.
AB  - Relationships between sediment toxicity and sediment chemistry were evaluated for
      98 samples collected from seven metropolitan study areas across the United
      States. Sediment-toxicity tests were conducted with the amphipod Hyalella azteca
      (28 day exposures) and with the midge Chironomus dilutus (10 day exposures).
      Overall, 33 % of the samples were toxic to amphipods and 12 % of the samples were
      toxic to midge based on comparisons with reference conditions within each study
      area. Significant correlations were observed between toxicity end points and
      sediment concentrations of trace elements, polycyclic aromatic hydrocarbons
      (PAHs), polychlorinated biphenyls (PCBs), or organochlorine (OC) pesticides;
      however, these correlations were typically weak, and contaminant concentrations
      were usually below sediment-toxicity thresholds. Concentrations of the pyrethroid
      bifenthrin exceeded an estimated threshold of 0.49 ng/g (at 1 % total organic
      carbon) in 14 % of the samples. Of the samples that exceeded this bifenthrin
      toxicity threshold, 79 % were toxic to amphipods compared with 25 % toxicity for
      the samples below this threshold. Application of mean probable effect
      concentration quotients (PECQs) based on measures of groups of contaminants
      (trace elements, total PAHs, total PCBs, OC pesticides, and pyrethroid pesticides
      [bifenthrin in particular]) improved the correct classification of samples as
      toxic or not toxic to amphipods compared with measures of individual groups of
      contaminants.

PMID- 23129065
TI  - Vincristine induces cell cycle arrest and apoptosis in SH-SY5Y human
      neuroblastoma cells.
AB  - Neuroblastoma is a common childhood tumor. Vincristine (VCR), an alkaloid
      extracted from Catharanthus roseus, is commonly used in combination chemotherapy.
      However, the mechanisms of VCR-induced neuroblastoma cell death are not clear.
      The aim of this study was to investigate the impact of VCR on mitosis and
      apoptosis of SH-SY5Y neuroblastoma cells and the underlying mechanisms. SH-SY5Y
      cells were treated with increasing VCR doses for different time points. Cell
      proliferation was detected using the MTT assay. Mitotic rate was quantified by
      immunofluorescence. Cell cycle and apoptosis were analyzed by flow cytometry. The
      mRNA and protein expression of caspase-3 and -9 (apoptotic factors), as well as
      cyclin B and D (cell cycle factors), was evaluated by real-time (RT)-PCR and
      western blot analysis, respectively. VCR inhibited SH-SY5Y cell proliferation in
      a time- and dose-dependent manner (P<0.05). The IC50 of VCR in SH-SY5Y cells was
      determined as 0.1 uM. VCR at 0.1 uM induced mitotic arrest and apoptosis,
      promoted the expression of caspase-3 and -9 and cyclin B, while decreasing the
      expression of cyclin D at 6, 12, 18 and 24 h. Except for the mRNA expression of
      cyclin D at 6 h, these changes were significant at both the mRNA and protein
      levels (P<0.05). VCR induces mitotic arrest of SH-SY5Y cells by regulating cyclin
      B and D. It further induces apoptosis in these cells through the activation of
      caspase-3 and -9. This study provides fundamental evidence for the application of
      VCR in neuroblastoma chemotherapy.

PMID- 23129066
TI  - [Sedation and weaning in neurocritical care: can concepts from general critical
      care be applied?].
AB  - The translation of modern principles of sedation and weaning from mechanical
      ventilation from general intensive care to neurocritical care has to take into
      account specific aspects of brain-injured patients. These include interactions
      with intracranial hypertension, disturbed autoregulation, a higher frequency of
      seizures and an increased risk of delirium. The advantages of sedation protocols,
      scoring tools to steer sedation and analgesia and an individualized choice of
      drugs with emphasis on analgesia gain more interest and importance in
      neurocritical care as well, but have not been thoroughly investigated so far.
      When weaning neurological intensive care unit (ICU) patients from the ventilator
      and approaching extubation it has to be acknowledged that conventional ICU
      criteria for weaning and extubation can only have an orienting character and that
      dysphagia is much more frequent in these patients.

PMID- 23129067
TI  - Adverse neurological outcomes in Nigerian children with sickle cell disease.
AB  - Sickle cell disease (SCD) is reported to be the most common genetic disorder
      affecting Nigerians. Children with SCD are at a high risk of neurological
      morbidity. The main objective of this study was to determine the pattern of
      adverse neurological outcomes among a cohort of Nigerian children with SCD. All
      children with SCD seen in the Department of Paediatrics, University College
      Hospital, Ibadan, Nigeria, over a period of 2 years were carefully evaluated for
      symptoms and signs of neurological complications, defined as clinical outcomes
      referable to the central nervous system. Of the 214 children evaluated, 187 were
      diagnosed with Hb SS disease and 27 with Hb SC disease. Neurological
      complications were identified in 78 (36.4 %) of the cases. The most common
      complications were headache (17.8 %), seizure (9.3 %) and stroke (8.4 %). Other
      less frequent complications included bacterial meningitis (2.8 %), spontaneous
      visual loss (1.4 %), paraplegia (0.9 %) and transient ischaemic attacks (0.9 %).
      Neurological complications occurred more frequently in children with sickle cell
      anaemia than in those with Hb SC disease (P = 0.002, 95 % CI 1.450-82.870).
      Adverse neurological events are common in Nigerian children with SCD, with a
      significantly higher risk in Hb SS than Hb SC disease. Stroke represents a major
      underlying cause of symptomatic epilepsy in SCD. Institution of primary
      preventive measures for stroke in SCD will significantly reduce the burden of
      stroke and epilepsy associated with SCD in Nigeria.

PMID- 23129068
TI  - Parental and other factors associated with hydroxyurea use for pediatric sickle
      cell disease.
AB  - BACKGROUND: Hydroxyurea (HU) is highly effective treatment for sickle cell
      disease (SCD). While pediatric use of HU is accepted clinical practice, barriers
      to use may impede its potential benefit. PROCEDURE: A survey of parents of
      children ages 5-17 years with SCD was performed across five institutions to
      assess factors associated with HU use. RESULTS: Of the 173 parent responses, 65
      (38%) had children currently taking HU. Among parents of children not taking HU,
      the most commonly cited reasons were that their hematology provider had not
      offered it, their child was not sufficiently symptomatic and concerns about
      potential side effects. Even parents of HU users reported widespread concern
      about effectiveness, long-term safety, and off-label use. In bivariate analyses,
      children's ages, parental demographics such as education level, or travel time to
      their hematology provider were not correlated with HU use. Bivariate analysis and
      multivariate logistic regression revealed three significant factors associated
      with current HU use: better parental knowledge about its major therapeutic
      effects (P < 0.001), sickle genotype (P = 0.005), and institution of clinical
      care (P = 0.04). CONCLUSIONS: Pervasive concerns about HU safety exist, even
      among parents of current users. Varying knowledge among parents appears to be
      independent of their demographics, and is associated with HU use. Inter
      institutional variability in parental knowledge and drug uptake highlights
      potentially potent site-specific influences on likelihood of HU use. Overall,
      these survey data underscore the need for strategies to bolster parental
      understanding about benefits of HU and address concerns about its safety.

PMID- 23129069
TI  - Extent of local invasion and safe resection in cT1-2 tonsil cancer.
AB  - BACKGROUND: Although intraoral resection of small-sized tonsil cancer achieves
      excellent tumor control, the extent of local invasion and adequate safety margin
      in resection have not been studied. Thus, we aim to determine the extent of local
      invasion in terms of mucosal spread and deep infiltration in stage T1-2 tonsil
      cancer. METHODS: We re-analyzed the surgical specimens from 49 cT1-2 tonsil
      cancers. Microscopic tumor cell extension from the tumor gross boundary of
      specimens was assessed in representative sections of each tumor. We also tested
      whether local extension correlates with human papilloma virus (HPV) status of
      tumors. RESULTS: The extent of microscopic deep invasion from the gross tumor
      border was 0.52 +/- 0.41 mm, which was significantly less than that of mucosal
      spread (0.83 +/- 0.61 mm, P = 0.01) in cT1-2 tonsil cancer. The microscopic deep
      invasion correlated with tumor size (rho = 0.703, P < 0.001). We found tumor
      invasion into superior constrictor muscles in 58.1%, no cases of tumor invasion
      into the deep fascia. In terms of HPV status (genotyping plus p16 staining),
      there were no differences in microscopic tumor extension. CONCLUSION: Our
      detailed pathologic analyses confirm that an oropharyngectomy including the
      superior constrictor muscle is an oncologically safe procedure for stage T1-2
      tonsil cancer.

PMID- 23129070
TI  - Booster seat laws and fatalities in children 4 to 7 years of age.
AB  - OBJECTIVE: To determine whether state booster seat laws were associated with
      decreased fatality rates in children 4 to 7 years of age in the United States.
      METHODS: Retrospective, longitudinal analysis of all motor vehicle occupant
      crashes involving children 4 to 7 years of age identified in the Fatality
      Analysis Reporting System from January 1999 through December 2009. The main
      outcome measure was fatality rates of motor vehicle occupants aged 4 to 7 years.
      Because most booster laws exclude children 6 to 7 years of age, we performed
      separate analyses for children 4 to 5, 6, and 7 years of age. RESULTS: When
      controlling for other motor vehicle legislation, temporal and economic factors,
      states with booster seat laws had a lower risk of fatalities in 4- to 5-year-olds
      than states without booster seat laws (adjusted incidence rate ratio 0.89; 95%
      confidence interval [CI] 0.81-0.99). States with booster seat laws that included
      6-year-olds had an adjusted incidence rate ratio of 0.77 (95% CI 0.65-0.91) for
      motor vehicle collision fatalities of 6-year-olds and those that included 7-year
      olds had an adjusted incidence rate ratio of 0.75 (95% CI, 0.62-0.91) for motor
      vehicle collision fatalities of 7-year-olds. CONCLUSIONS: Booster seat laws are
      associated with decreased fatalities in children 4 to 7 years of age, with the
      strongest association seen in children 6 to 7 years of age. Future legislative
      efforts should extend current laws to children aged 6 to 7 years.

PMID- 23129071
TI  - A quality improvement project to increase breast milk use in very low birth
      weight infants.
AB  - OBJECTIVE: To evaluate a multihospital collaborative designed to increase breast
      milk feeding in premature infants. METHODS: Eleven NICUs in the California
      Perinatal Quality of Care Collaborative participated in an Institute for
      Healthcare Improvement-style collaborative to increase NICU breast milk feeding
      rates. Multiple interventions were recommended with participating sites
      implementing a self-selected combination of these interventions. Breast milk
      feeding rates were compared between baseline (October 2008-September 2009),
      implementation (October 2009-September 2010), and sustainability periods (October
      2010-March 2011). Secondary outcome measures included necrotizing enterocolitis
      (NEC) rates and lengths of stay. California Perinatal Quality of Care
      Collaborative hospitals not participating in the project served as a control
      population. RESULTS: The breast milk feeding rate in the intervention sites
      improved from baseline (54.6%) to intervention period (61.7%; P = .005) with
      sustained improvement over 6 months postintervention (64.0%; P = .003). NEC rates
      decreased from baseline (7.0%) to intervention period (4.3%; P = .022) to
      sustainability period (2.4%; P < .0001). Length of stay increased during the
      intervention but returned to baseline levels in the sustainability period.
      Control hospitals had higher rates of breast milk feeding at baseline (64.2%
      control vs 54.6% participants, P < .0001), but over the course of the
      implementation (65.7% vs 61.7%, P = .049) and sustainability periods (67.7% vs
      64.0%, P = .199), participants improved to similar rates as the control group.
      CONCLUSIONS: Implementation of a breast milk/nutrition change package by an 11
      site collaborative resulted in an increase in breast milk feeding and decrease in
      NEC that was sustained over an 18-month period.

PMID- 23129072
TI  - Newborn, carrier, and early childhood screening recommendations for fragile X.
AB  - Fragile X syndrome, diagnosed by Fragile X Mental Retardation 1 (FMR1) DNA
      testing, is the most common single-gene cause of inherited intellectual
      disability. The expanded CGG mutation in the FMR1 gene, once thought to have
      clinical significance limited to fragile X syndrome, is now well established as
      the cause for other fragile X-associated disorders including fragile X-associated
      primary ovarian insufficiency and fragile X-associated tremor ataxia syndrome in
      individuals with the premutation (carriers). The importance of early diagnostic
      and management issues, in conjunction with the identification of family members
      at risk for or affected by FMR1 mutations, has led to intense discussion about
      the appropriate timing for early identification of FMR1 mutations. This review
      includes an overview of the fragile X-associated disorders and screening efforts
      to date, and discussion of the advantages and barriers to FMR1 screening in
      newborns, during childhood, and in women of reproductive age. Comparison with
      screening programs for other common genetic conditions is discussed to arrive at
      action steps to increase the identification of families affected by FMR1
      mutations.

PMID- 23129073
TI  - Identifying teens at risk: developmental pathways of online and offline sexual
      risk behavior.
AB  - OBJECTIVES: The aims of this study were (1) to investigate the prevalence and
      development of both online (OnSRB) and offline sexual risk behavior (OffSRB) in
      adolescence, (2) to establish whether OnSRBs and OffSRBs are related, and (3) to
      identify risk factors that determine problematic pathways of OnSRB and OffSRB.
      METHODS: A 4-wave longitudinal study with 1762 Dutch adolescents aged 12 to 18
      was conducted (mean age, T1 = 14.52, 49% girls). By using group-based modeling,
      developmental pathways for OnSRB and OffSRB were identified and the relationship
      between both behaviors over time was examined. RESULTS: Substantial
      intraindividual differences in the development of OnSRB and OffSRB were found.
      The analysis revealed 3 developmental pathways of OnSRB: no risk (70.2%),
      moderate risk (23.7%), and high risk (6.1%). For OffSRB, we identified a no risk
      (90.6%) and an increasing pathway (9.4%). OnSRBs and OffSRBs were related and had
      common predictors (ie, sensation seeking, low educational level, gender).
      CONCLUSIONS: Only a minority of adolescents shows sustained high OnSRB. This
      group is likely to consist of low-educated, high-sensation-seeking adolescents
      who spend more time communicating on the Internet and come from less cohesive
      families. These same adolescents are also more likely to engage in OffSRB.
      Preventions should focus on these adolescents.

PMID- 23129074
TI  - Differing attitudes toward fetal care by pediatric and maternal-fetal medicine
      specialists.
AB  - OBJECTIVES: The expansion of pediatric-based fetal care raises questions
      regarding pediatric specialists' involvement in pregnancies when maternal
      conditions may affect pediatric outcomes. For several such conditions, we
      compared pediatric and obstetric specialists' attitudes regarding whether and
      when pediatrics consultation should be offered and their views about seeking
      court authorization to override maternal refusal of physician recommendations.
      METHODS: We used a mail survey of 434 maternal-fetal medicine specialists (MFMs)
      and fetal care pediatric specialists (FCPs) (response rate: MFM, 60.9%; FCP,
      54.2%). RESULTS: FCPs were more likely than MFMs to indicate that pediatric
      counseling should occur before decisions regarding continuing or interrupting
      pregnancies complicated by maternal alcohol abuse (FCP versus MFM: 63% vs 36%),
      cocaine abuse (FCP versus MFM: 60% vs 32%), use of seizure medications (FCP
      versus MFM: 62% vs 33%), and diabetes (FCP versus MFM: 56% vs 27%) (all P <
      .001). For all conditions, MFMs were more than twice as likely as FCPs to think
      that no pediatric specialist consultation was ever necessary. FCPs were more
      likely to agree that seeking court interventions was appropriate for maternal
      refusal to enter a program to discontinue cocaine use (FCP versus MFM: 72% vs
      33%), refusal of azidothymidine to prevent perinatal HIV transmission (80% vs
      41%), and refusal of percutaneous transfusion for fetal anemia (62% vs 28%) (all
      P < .001). CONCLUSIONS: Pediatric and obstetric specialists differ considerably
      regarding pediatric specialists' role in prenatal care for maternal conditions,
      and regarding whether to seek judicial intervention for maternal refusal of
      recommended treatment.

PMID- 23129075
TI  - Impact of a third dose of measles-mumps-rubella vaccine on a mumps outbreak.
AB  - BACKGROUND AND OBJECTIVE: During 2009-2010, a northeastern US religious community
      experienced a large mumps outbreak despite high 2-dose measles-mumps-rubella
      (MMR) vaccine coverage. A third dose of MMR vaccine was offered to students in an
      affected community in an effort to control the outbreak. METHODS: Eligible sixth-
      to 12th-grade students in 3 schools were offered a third dose of MMR vaccine.
      Baseline and follow-up surveys and physician case reports were used to monitor
      mumps attack rates (ARs). We calculated ARs for defined 3-week periods before and
      after the intervention. RESULTS: Of 2265 eligible students, 2178 (96.2%) provided
      documentation of having received 2 previous doses of MMR vaccine, and a high
      proportion (1755 or 80.6%) chose to receive an additional vaccine dose. The
      overall AR for all sixth- to 12th-grade students declined from 4.93% in the
      prevaccination period to 0.13% after vaccination (P < .001). Villagewide, overall
      AR declined by 75.6% after the intervention. A decline occurred in all age groups
      but was significantly greater (96.0%) among 11- to 17-year-olds, the age group
      targeted for vaccination, than among all other age groups. The proportions of
      adverse events reported were lower than or within the range of those in previous
      reports of first- and second-dose MMR vaccine studies. CONCLUSIONS: This is the
      first study to assess the impact of a third MMR vaccine dose for mumps outbreak
      control. The decline in incidence shortly after the intervention suggests that a
      third dose of MMR vaccine may help control mumps outbreaks among populations with
      preexisting high 2-dose vaccine coverage.

PMID- 23129076
TI  - Common variable immunodeficiency presenting with persistent parvovirus B19
      infection.
AB  - Parvovirus B19 infection in healthy hosts is self-limited, but persistent
      infection has been described in patients with cellular immune defects. A 6-year
      old boy presented with a 6-month history of weight loss and malaise and a 1-month
      history of fever and polyarticular arthritis. Parvovirus DNA was detected in
      plasma at 10 300 copies/mL. Levels of immunoglobulin (Ig)G, IgA, IgM, IgG-1, and
      IgG-2 were low, and antibody responses to vaccine antigens were impaired. HIV
      antibody and DNA polymerase chain reaction were negative, and the patient had
      normal immunophenotype, mitogen stimulation response, CD40 ligand and inducible
      costimulator expression, transmembrane activator and CAML interactor sequencing,
      genomic analysis, and fluorescent in situ hybridization for deletions at 22q11.2.
      Common variable immunodeficiency was diagnosed and replacement therapy with
      immune globulin intravenous was initiated. The parvovirus DNA level declined by
      half over 3 months and was undetectable at 15 months. Constitutional symptoms
      improved but arthritis persisted and eosinophilic fasciitis eventually developed.
      This case demonstrates that persistent parvovirus infection may be a presenting
      feature of humoral immune deficiency and can mimic juvenile rheumatoid arthritis.
      The infection may respond to immune globulin intravenous therapy.

PMID- 23129077
TI  - Arrhythmia associated with tetracaine in an extremely low birth weight premature
      infant.
AB  - Infants in NICUs undergo a variety of painful procedures. The management of pain
      has become an integral part of newborn infant care with the use of both systemic
      and topical agents to provide analgesia and anesthesia for procedural pain.
      Tetracaine and prilocaine-lidocaine are the 2 topical anesthetics most frequently
      used. Tetracaine belongs to an ester group of local anesthetics available as a
      topical 4% gel (Ametop, Smith and Nephew, Canada). The major side effects
      reported when using topical anesthetics are cutaneous reactions. There are no
      definite reports of systemic toxicity in the published literature. We present a
      recent case of an extremely low birth weight premature infant who developed a
      clinically significant arrhythmia after topical tetracaine was applied before the
      insertion of a peripherally inserted central catheter. The infant had no other
      identifiable cause for the resulting bradycardia that occurred only after Ametop
      was applied. The cardiac symptoms resolved with treatment. This case highlights a
      significant potential adverse event when using topical tetracaine.

PMID- 23129079
TI  - Buprenorphine may not be as safe as you think: a pediatric fatality from
      unintentional exposure.
AB  - Buprenorphine is a partial MU-opioid receptor agonist that is approved for the
      treatment of opioid dependency. It is generally believed to be safer than
      methadone because of its ceiling effect on respiratory depression. As more adults
      in US households use buprenorphine, an increasing number of children are being
      exposed. We report a fatal exposure to buprenorphine in a small child that
      occurred after ingestion of a caretaker's buprenorphine/naloxone. Postmortem
      toxicology analysis showed free serum concentrations of 52 ng/mL and 39 ng/mL for
      buprenorphine and norbuprenorphine, respectively. No other drugs were detected.
      Autopsy did not find signs of injury or trauma. The theoretical safety provided
      by the ceiling effect in respiratory depression from buprenorphine may not apply
      to children, and buprenorphine may cause dose-dependent respiratory depression.

PMID- 23129078
TI  - Hospitalization of rural and urban infants during the first year of life.
AB  - OBJECTIVES: To examine hospitalizations and length of stay (LOS) for infants aged
      <1 year in rural and urban counties, hypothesizing that infants living in rural
      counties experience significantly different hospital use compared with urban
      infants. METHODS: Birth certificates for infants born in California hospitals
      between 1993 and 2005 and surviving to discharge were linked to hospital
      discharge records and death certificates during the first year of life, resulting
      in a study population of >6.4 million. Hospitalizations, cumulative LOS,
      readmission rates, and mortality were compared by using univariate and
      multivariable analysis for infants living in small rural, large rural, small
      urban, and large urban counties. Odds of hospitalization and cumulative LOS were
      also examined for common infant diagnoses. RESULTS: Infants living in
      increasingly rural counties experienced decreasing rates of hospitalization and
      decreasing number of hospitalized days during the first year of life. Infants
      living in small rural counties experienced 370 hospital days per 1000 infants
      compared with 474 hospital days per 1000 infants living in large urban counties.
      In multivariable analysis, infants in large urban counties experienced increased
      odds of hospitalization (odds ratio: 1.20 [95% confidence interval: 1.06-1.36])
      and increased hospitalized days (incidence risk ratio: 1.17 [95% confidence
      interval: 1.06-1.29]) compared with infants in small rural counties. For most
      common diagnoses, urban residence was associated with either increased odds of
      hospitalization or increased cumulative LOS. CONCLUSIONS: Infants living in rural
      California counties experienced decreased hospital utilization, including
      decreased hospitalization and decreased LOS, compared with infants living in
      urban counties.

PMID- 23129080
TI  - 15-year follow-up of recurrent "hypoglycemia" in preterm infants.
AB  - BACKGROUND: Observational study of 543 infants who weighed <1850 g, published in
      1988 reported seriously impaired motor and cognitive development at 18 months in
      those with recurrent, asymptomatic hypoglycemia (plasma glucose level <=2.5
      mmol/L on >=3 days). No study has yet replicated this observation. AIM: To
      quantify disability in a similar cohort of children followed up throughout
      childhood. POPULATION: All children born at <32 weeks' gestation in the north of
      England in 1990-1991 and had laboratory blood glucose levels measured daily for
      the first 10 days of life. RESULTS: Forty-seven index children of the 566 who
      survived to 2 years had a blood glucose level of <=2.5 mmol/L on >=3 days. All of
      these children and hypoglycemia-free controls, matched for hospital of care,
      gestation, and birth weight, were assessed at age 2. No differences in
      developmental progress or physical disability were detected. The families were
      seen again when the children were 15 years old, and 38 of the index children
      (81%) and matched controls agreed to detailed psychometric assessment. Findings
      in the 2 groups were nearly identical (mean full-scale IQ: 80.7 vs 81.2).
      Findings in the 21 children with a level of <=2.5 mmol/L on >=4 days, 7 children
      with a level this low on 5 days, and 11 children with a level of <2.0 mmol/L on 3
      different days did not alter these conclusions. CONCLUSIONS: This study found no
      evidence to support the belief that recurrent low blood glucose levels (<=2.5
      mmol/L) in the first 10 days of life usually pose a hazard to preterm infants.

PMID- 23129082
TI  - Clinical tracking of severely obese children: a new growth chart.
AB  - The 2000 Centers for Disease Control and Prevention growth charts are unable to
      accurately define and display BMI percentiles beyond the 97th percentile. At
      Children's Hospital Colorado, we created new growth charts that allow clinicians
      to track and visualize BMI values in severely obese children. This growth chart
      defines a child's BMI as a "percentage of the 95th percentile." It has the
      potential to allow clinicians to define subgroups of severe obesity, monitor
      trends in obese children, and measure treatment success or failure.

PMID- 23129081
TI  - Predictors of delayed or forgone needed health care for families with children.
AB  - BACKGROUND: We sought to determine how health care-related financial burden,
      childhood activity limitations, health insurance, and other access-related
      factors predict delayed or forgone care for families with children, using a
      nationally representative, population-based sample. METHODS: Our sample included
      families with children aged 0 to 17 years whose family was interviewed about
      their health care expenditures in 1 of 7 panels of the 2001 to 2008 Medial
      Expenditure Panel Survey (N = 14 138). Financial burden was defined as (1) the
      sum of out-of-pocket health service expenditures during the first survey year and
      (2) that sum divided by adjusted family income. Delayed or forgone care was
      defined as self-report of delayed or forgone medical care or prescription
      medications for the reference parent or child during the second survey year.
      RESULTS: Financial burden, discordant insurance, and having a child with an
      activity limitation were some of the strongest predictors of delayed or forgone
      care. Additionally, significant health insurance and income-related disparities
      exist in the experience of delayed or forgone care. CONCLUSIONS: Children and
      their families are delaying or forgoing needed care due to health care-related
      financial burden. Policies are needed to effectively reduce financial burden and
      improve the concordance of insurance between parents and children because this
      may reduce the frequency of unmet need among families. Moreover, reducing the
      occurrence of delayed or forgone care may improve health outcomes by increasing
      the opportunity to receive timely and preventive care.

PMID- 23129083
TI  - Health-related quality of life in children and adolescents with Duchenne muscular
      dystrophy.
AB  - OBJECTIVES: The purpose of this study was to assess health-related quality of
      life (QoL) in children with Duchenne muscular dystrophy (DMD), including
      development and field-testing of a DMD-specific module integrated with the core
      Pediatric Quality of Life Inventory (PedsQL). METHODS: The PedsQL 4.0 Generic
      Core and DMD Module Scales were completed by 203 families, including 200 parents
      and 117 boys with DMD. Scores on the PedsQL Core Scales were compared with those
      of matched healthy children. Relationships between PedsQL scores and patient
      characteristics were examined. RESULTS: By both parent report and child self
      report, mean PedsQL scores for boys with DMD were significantly lower than those
      for healthy children for physical and psychosocial QoL (P < .0001), with
      significantly impaired psychosocial QoL scores self-reported by 57%. Psychosocial
      QoL, by self-report only, tended to be higher in the older boys (13-18 years)
      than in younger boys (8-12 years; P = .05) and was not significantly associated
      with use of mobility aids. Although parents reported higher Daily Activities
      scores in boys receiving steroids (P = .01), boys receiving steroids reported no
      difference in Daily Activities but significantly less worry (P = .004). Parent
      child concordance was generally in the fair to poor range. Internal consistency
      reliability coefficients for PedsQL DMD module scales ranged from 0.66 to 0.86.
      CONCLUSIONS: Overall, boys with DMD reported significantly lower QoL than their
      healthy peers. Despite decreased physical functioning, older boys seem to
      perceive better psychosocial QoL than perceived by their parents and by younger
      boys, unrelated to their need for mobility aids.

PMID- 23129084
TI  - Long-term benefits of home-based preventive care for preterm infants: a
      randomized trial.
AB  - BACKGROUND: We have previously reported improved caregiver mental health and
      infant behavior at 2 years following a home-based preventive care program for
      very preterm infants and their caregivers. This study aimed to determine the
      longer-term effectiveness of the program by reviewing caregivers and children at
      preschool age. METHODS: One hundred twenty very preterm infants (<30 weeks'
      gestation) were randomly allocated to intervention (n = 61) or control (n = 59)
      groups. The intervention included 9 home visits over the first year of life
      targeting infant development, parent mental health, and the parent-infant
      relationship. The control group received standard care. At 4 years' corrected
      age, child cognitive, behavioral, and motor functioning and caregiver mental
      health were assessed. RESULTS: At age 4 years, 105 (89%) children were reviewed.
      There was little evidence of differences in cognitive or motor functioning
      between groups. The intervention group had lower scores for child internalizing
      behaviors than the control group (mean difference -5.3, 95% confidence interval
      [CI] -9.6 to -0.9, P = .02). Caregivers in the intervention group had fewer
      anxiety symptoms (mean difference -1.8, 95% CI -3.3 to -0.4, P = .01) and were
      less likely to exhibit "at-risk" anxiety (odds ratio 0.3, 95% CI 0.1 to 0.7, P =
      .01) than those in the control group. CONCLUSIONS: This home-based preventive
      care program for very preterm infants has selective long-term benefits, including
      less caregiver anxiety and reduced preschooler internalizing behaviors.

PMID- 23129085
TI  - Office-based randomized controlled trial to reduce screen time in preschool
      children.
AB  - OBJECTIVE: To determine if an intervention for preschool-aged children in primary
      care is effective in reducing screen time, meals in front of the television, and
      BMI. METHODS: A randomized controlled trial was conducted at a primary care
      pediatric group practice in Toronto, Canada. Three-year-old children and their
      parents were randomly assigned to receive a short behavioral counseling
      intervention on strategies to decrease screen time. The primary outcome 1 year
      later was parent reported screen time. Secondary outcomes included television in
      the child's bedroom, number of meals in front of the television, and BMI.
      RESULTS: In the intention-to-treat analysis at 1 year, there were no significant
      differences in mean total weekday minutes of screen time (60, interquartile range
      [IQR]: 35-120 vs 65, IQR: 35-120; P = .68) or mean total weekend day minutes of
      screen time (80, IQR: 45-130 vs 90, IQR: 60-120; P = .33) between the
      intervention and control group. Adjusting for baseline BMI, there was a reduction
      in the number of weekday meals in front of the television (1.6 +/- 1.0 vs 1.9 +/-
      1.2; P = .03) but no differences in BMI or number of televisions in the bedroom.
      CONCLUSIONS: This pragmatic trial was not effective in reducing screen time or
      BMI but was effective in reducing meals in front of the screen. Short
      interventions focused solely on reducing screen time implemented in the primary
      care practice setting may not be effective in this age group.

PMID- 23129086
TI  - Detection of viruses in young children with fever without an apparent source.
AB  - OBJECTIVE: Fever without an apparent source is common in young children.
      Currently in the United States, serious bacterial infection is unusual. Our
      objective was to determine specific viruses that might be responsible. METHODS:
      We enrolled children aged 2 to 36 months with temperature of 38 degrees C or
      greater without an apparent source or with definite or probable bacterial
      infection being evaluated in the St Louis Children's Hospital Emergency
      Department and afebrile children having ambulatory surgery. Blood and
      nasopharyngeal swab samples were tested with an extensive battery of virus
      specific polymerase chain reaction assays. RESULTS: One or more viruses were
      detected in 76% of 75 children with fever without an apparent source, 40% of 15
      children with fever and a definite or probable bacterial infection, and 35% of
      116 afebrile children (P < .001). Four viruses (adenovirus, human herpesvirus 6,
      enterovirus, and parechovirus) were predominant, being detected in 57% of
      children with fever without a source, 13% of children with fever and definite or
      probable bacterial infection, and 7% of afebrile children (P < .001). Thirty-four
      percent of 146 viral infections were detected only by polymerase chain reaction
      performed on blood. Fifty-one percent of children with viral infections and no
      evidence of bacterial infection were treated with antibiotics. CONCLUSIONS: Viral
      infections are frequent in children with fever without an apparent source.
      Testing of blood in addition to nasopharyngeal secretions expanded the range of
      viruses detected. Future studies should explore the utility of testing for the
      implicated viruses. Better recognition of viruses that cause undifferentiated
      fever in young children may help limit unnecessary antibiotic use.

PMID- 23129087
TI  - The globalization of pediatric clinical trials.
AB  - OBJECTIVE: To examine the characteristics of pediatric trials conducted under US
      legislation and to compare results with data from 2002 to 2007. METHODS: We
      reviewed all pediatric trials provided to the US Food and Drug Administration in
      submissions that were approved between September 28, 2007 and December 21, 2010.
      We extracted data for each trial including age range, therapeutic indication,
      design, duration, and patient and center enrollment by location. RESULTS: Overall
      346 studies on 113 drugs and biologicals enrolled 55 819 pediatric patients. The
      United States participated in 86% of the studies, providing 71% of the centers
      and 74% of the patients. Corresponding percentages for non-US countries were 43%,
      29%, and 26% respectively. Developing or transition countries participated in 22%
      of the studies, providing 12% of the centers and 10% of the patients; our earlier
      analysis found corresponding percentages of 38%, 12%, and 23%. The most common
      therapeutic areas studied in the latter countries were infectious, neurologic,
      and pulmonary diseases. Seventy-eight vaccine studies enrolled 147 692 patients.
      The United States participated in 40% of the studies, providing 39% of the
      centers and 22% of the patients. Corresponding percentages for non-US countries
      were 74%, 61%, and 78% respectively. Developing or transition countries
      participated in 27% of the studies, providing 15% of the centers and 52% of the
      patients. CONCLUSIONS: The United States remains an important location for
      pediatric trials. Developing country involvement in pediatric drug development is
      not increasing, although these countries participate significantly in vaccine
      trials.

PMID- 23129088
TI  - DDQ-catalyzed oxidative C--O coupling of sp3 C--H bonds with carboxylic acids.

PMID- 23129089
TI  - Low total haemoglobin mass, blood volume and aerobic capacity in men with type 1
      diabetes.
AB  - Blood O2 carrying capacity affects aerobic capacity (VO2max). Patients with type
      1 diabetes have a risk for anaemia along with renal impairment, and they often
      have low VO2max. We investigated whether total haemoglobin mass (tHb-mass) and
      blood volume (BV) differ in men with type 1 diabetes (T1D, n = 12) presently
      without complications and in healthy men (CON, n = 23) (age-, anthropometry-,
      physical activity-matched), to seek an explanation for low VO2max. We determined
      tHb-mass, BV, haemoglobin concentration ([Hb]), and VO2max in T1D and CON. With
      similar (mean +/- SD) [Hb] (144 vs. 145 g l(-1)), T1D had lower tHb-mass (10.1 +/
      1.4 vs. 11.0 +/- 1.1 g kg(-1), P < 0.05), BV (76.8 +/- 9.5 vs. 83.5 +/- 8.3 ml
      kg(-1), P < 0.05) and VO2max (35.4 +/- 4.8 vs. 44.9 +/- 7.5 ml kg(-1) min(-1), P
      < 0.001) than CON. VO2max correlated with tHb-mass and BV both in T1D (r = 0.71,
      P < 0.01 and 0.67, P < 0.05, respectively) and CON (r = 0.54, P < 0.01 and 0.66,
      P < 0.001, respectively), but not with [Hb]. Linear regression slopes were
      shallower in T1D than CON both between VO2max and tHb-mass (2.4 and 3.6 ml kg(-1)
      min(-1) vs. g kg(-1), respectively) and VO2max and BV (0.3 and 0.6 ml kg(-1) min(
      1) vs. g kg(-1), respectively), indicating that T1D were unable to reach similar
      VO2max than CON at a given tHb-mass and BV. In conclusion, low tHb-mass and BV
      partly explained low VO2max in T1D and may provide early and more sensitive
      markers of blood O2 carrying capacity than [Hb] alone.

PMID- 23129091
TI  - Delphinidin induces autolysosome as well as autophagosome formation and
      delphinidin-induced autophagy exerts a cell protective role.
AB  - Anthocyanidins, which are polyphenols that are believed to be effective for
      preventing cancer, are composed of a basic structure of the plant pigment
      anthocyanin. In this study, we investigated the biological activity of
      anthocyanidins, including delphinidin, against HeLa cells. The cytotoxicity
      observed in the anthocyanidins-treated cells was well correlated with the
      inhibitory effects of anthocyanidins on c-Jun-dependent transcriptional activity.
      Remarkably, anthocyanidin induced autophagosome formation but lacked the ability
      to induce apoptosis. Notably, delphinidin enhanced autolysosome formation as well
      as autophagosome formation. Delphinidin treatment resulted in the accumulation of
      the lipidated form of Map1lc3b protein in an Atg5-dependent manner in mouse
      embryonic fibroblasts. Finally, we revealed that the cytotoxicity induced by
      delphinidin was more severe in Atg5-deficient mouse embryonic fibroblasts than in
      wild-type cells. Taken together, these results indicate that the cytotoxicity
      induced by delphinidin was accompanied by autophagy and delphinidin-induced
      autophagy exerted a cell protective role.

PMID- 23129090
TI  - Exercise-induced myofibrillar disruption with sarcolemmal integrity prior to
      simulated diving has no effect on vascular bubble formation in rats.
AB  - Decompression sickness is initiated by gas bubbles formed during decompression,
      and it has been generally accepted that exercise before decompression causes
      increased bubble formation. There are indications that exercise-induced muscle
      injury seems to be involved. Trauma-induced skeletal muscle injury and vigorous
      exercise that could theoretically injure muscle tissues before decompression have
      each been shown to result in profuse bubble formation. Based on these findings,
      we hypothesized that exercise-induced skeletal muscle injury prior to
      decompression from diving would cause increase of vascular bubbles and lower
      survival rates after decompression. In this study, we examined muscle injury
      caused by eccentric exercise in rats prior to simulated diving and we observed
      the resulting bubble formation. Female Sprague-Dawley rats (n = 42) ran downhill
      (-16o) for 100 min on a treadmill followed by 90 min rest before a 50-min
      simulated saturation dive (709 kPa) in a pressure chamber. Muscle injury was
      evaluated by immunohistochemistry and qPCR, and vascular bubbles after diving
      were detected by ultrasonic imaging. The exercise protocol resulted in increased
      mRNA expression of markers of muscle injury; alphaB-crystallin, NF-kappaB, and
      TNF-alpha, and myofibrillar disruption with preserved sarcolemmal integrity.
      Despite evident myofibrillar disruption after eccentric exercise, no differences
      in bubble amounts or survival rates were observed in the exercised animals as
      compared to non-exercised animals after diving, a novel finding that may be
      applicable to humans.

PMID- 23129092
TI  - International regulations on labour health and safety applied to fishing and
      maritime transport sectors. Are maritime workers under-protected.
AB  - The work activity developed on board is of great importance in our nearby
      environment, and it has a series of peculiarities that determine the service
      rendering of sea workers. On the other hand, work at sea is developed on an
      international basis. Nowadays such work becomes a completely globalised
      industrial sector in relation to the elements that make up the ship's operation,
      including manpower. For that reason several relevant international organisations
      have paid attention to this industrial sector and have adopted a broad regulation
      on this matter. In the case of the European Union, the Community procedure
      emphasises enormous interest in providing specific and comprehensive training to
      seafarers, as well as in regulating working time on board with the aim of
      minimising the safety problems caused by fatigue. In the present article a
      schematic presentation of regulations on workers' health and occupational safety
      protection derived from the European Union, the International Maritime
      Organisation, and the International Labour Organisation has been done. Also it
      shows what parts of these regulations are not applicable to the work on board,
      and it reveals how the workers of fishing and maritime transport sectors are
      under-protected with regard to the guarantee of their health and occupational
      safety compared to workers in other sectors.

PMID- 23129093
TI  - Communications strategies for on-ship CDPC systems.
AB  - BACKGROUND: Individual countries and international organisations have worked on
      standardising methods for on-ship prevention and control of communicable disease
      (CDPC). A number of voices have called for integrating the various aspects of
      maritime CDPC. AIM: The purpose of this article is to further conceptualise the
      totality of on-ship CDPC activity as an integrated system and to suggest a few
      strategies for communications in such systems. MATERIALS AND METHODS: The methods
      used to summarise standardisation and integration of ship-board CDPC procedures
      included a scientific literature review and a web search. The fields of the
      review were maritime, health, and technology sources. Special attention was paid
      to material dealing with communications methods and issues related to ship-board
      systems and methods to manage communicable diseases. RESULTS AND CONCLUSIONS:
      Effective communications strategies are vital for the success of CDPC systems. I
      suggest some specific viewpoints and strategies to improve communications: (i) It
      is sometimes helpful to view the Constituent Relations Management (CRM) team as a
      system component. This view highlights the fact that an on-ship CDPC system will
      be well designed and maintained only if constituent relations are well designed
      and maintained. (ii) For rapid communications with appropriate groups of
      constituents, it is important to structure groups of constituents, with the
      ability to rapidly apply set-theoretic operations to those groups. (iii)
      Optimistic concurrency control is generally the appropriate general strategy for
      synchronisation of on-ship CDPC data locations and data storage types. This may
      be modified in special situations, in particular with a latest-update-wins policy
      for disease contraction data in an epidemic. (iv) To encourage traveller
      cooperation with CDPC efforts, cultural activities may be helpful.

PMID- 23129094
TI  - Health effects due to fumigated freight containers and goods: how to detect, how
      to act.
AB  - Headache, concentration and memory disorders, dizziness and nausea, skin
      irritation, respiratory  distress, and muscle cramps - isolated or in various
      combinations - may be the result of  acute or chronic intoxication by fumigants.
      The occurrence of these symptoms in workers who  are engaged in the opening and
      unloading of containers, unpacking of imported goods, ventilating  of containers,
      or working on bulk carriers are urgent indications of intoxication by fumigants 
      or other toxic chemical residues in the transported goods. The severity of the
      disorder depends  on the concentration and duration of exposure, distribution and
      release of the fumigant, its  kinetics, the individual susceptibility of the
      person, as well as any simultaneous exposure to  other toxic substances. Physical
      symptoms, acute and chronic health effects due to contact with  fumigants, are
      complex and difficult to discover. In this article we explain how to identify the
      guiding symptoms and describe the appropriate diagnostic steps and the
      prevention of such  events on cargo vessels as well as in the logistics and the
      handling of imported goods.

PMID- 23129095
TI  - International Workshop 2011: "How to handle import containers safely".

PMID- 23129097
TI  - Risk factors for fishermen's health and safety in Greece.
AB  - BACKGROUND: This is, to the best of our knowledge, the first occupational health
      study in Greek fishing. AIM: The aim of the study is to determine the risks for
      health and safety in Greek fisheries workers by exploring their health status and
      the health risk factors present in their occupational environment, thus providing
      a current baseline for further research in the future and for documentation of
      the needs for prevention. MATERIALS AND METHODS: A questionnaire pilot study was
      carried out in a random sample of 100 Greek fishermen. RESULTS: Twenty-eight per
      cent (28%) had experienced at least one injury, of which half caused more than
      one day absence, while 14% had a near drowning experience. The health risks
      factors studied include excessive weight, cardiovascular incidents and
      dermatological, musculoskeletal, respiratory, hearing, stress, and anxiety
      problems. The occupational health risk factors include alcohol, fatty food
      consumption, smoking, and lack of physical exercise. CONCLUSIONS: The health
      effects observed are causally related to diet, smoking, and exercise, which in
      turn relate to the specific working conditions and culture in small-scale fishing
      that need to be taken into consideration in prevention programmes. The results
      are comparable with international fisheries experience, mainly from Poland,
      Denmark, and Turkey.

PMID- 23129098
TI  - International cooperation on research and health promotion in fishery.

PMID- 23129099
TI  - Cardiovascular risk factors and cardiovascular risk assessment in professional
      divers.
AB  - BACKGROUND: The professional diver's activity implies body cardiovascular stress.
      Little data on cardiovascular risk factors is available. Some studies report a
      high prevalence of tobacco consumption. The purpose of this study is to
      investigate the cardiovascular risk factors of professional divers and calculate
      the predicted 5-year risk and the predicted 10-year risk of an acute coronary
      event. MATERIALS AND METHODS: In one medical centre, data on dives and
      cardiovascular risk factors were analysed on Epidata((r)) software, by Pearson
      chi(2) test or by Fisher's exact test, by analysis of variance test or by Kruskal
      Wallis test, and by Spearman correlation coefficient. Cardiovascular risk scores
      at 5 and 10 years were calculated using SCORE. RESULTS: A total 200 professional
      divers were included. Of these, 31% were smokers or had stopped smoking for less
      than 3 years; 40% had an abnormal body mass index; 50% had raised total
      cholesterol levels; 11% had an advanced age; 6.5% had high blood pressure; 81%
      had at least one risk factor; 66% had an alterable risk factor; 25.5% had a 5
      year risk greater than that of the general population of the same age; 2.5% had a
      high cardiovascular risk at 10 years; and 34% were at intermediate risk.
      CONCLUSIONS: The majority of divers had at least one cardiovascular risk factor.
      Cardiovascular risk scores were lower than that of the general population.
      However, some of this population is at high risk. One third of the divers had an
      intermediate risk, which should lead to the consideration of conducting
      additional biological examinations to better assess their risk.

PMID- 23129100
TI  - Decompression sickness in urban divers in France.
AB  - BACKGROUND: Decompression sickness (DCS) can occur in SCUBA divers. DCS is
      treated with oxygen, preferably given under hyperbaric conditions. Although Paris
      (France) is located at a distance from the sea or lakes, some injured divers
      require hyperbaric oxygen treatment (HBOT) in this city, sometimes within a
      specific time frame. Thus, this study investigated the epidemiology and outcomes
      of such urban divers. AIM: We conducted an observational study of SCUBA divers
      admitted to the Raymond Poincare Hyperbaric centre near Paris from 1993 to 2003.
      MATERIALS AND METHODS: We prospectively enrolled 69 consecutive SCUBA divers
      presenting DCS. Common risk factors were reported, especially aeroplane flight
      and training dives. Symptoms are very often atypical (63%) and onset time of
      symptoms is often too long (59% after 2 h) due to denial of symptoms. First aid
      is generally inadequate, with only 23% of victims receiving oxygen, fluid loading
      and aspirin together. HBOT was given for 42 (61%) patients although their
      examination results were considered as normal. CONCLUSIONS: Diving pits and
      diving travel agencies should do more to warn divers of the need for treatment
      with normobaric oxygen and hydration pending HBOT. Moreover, hyperbaric
      physicians should better clarify HBOT indications for both symptoms of late onset
      and atypical presentations.

PMID- 23129101
TI  - Comparison of displacement and acceleration transducers for the characterization
      of mechanics of muscle and subcutaneous tissues by system identification of a
      mechanomyogram.
AB  - The purpose of this study was to clarify the performance of transducers for the
      mechanical characterization of muscle and subcutaneous tissue with the aid of a
      system identification technique. The common peroneal nerve was stimulated, and a
      mechanomyogram (MMG) of the anterior tibialis muscle was detected with a laser
      displacement meter or an acceleration sensor. The transfer function between
      stimulation and the MMG was identified by the singular value decomposition
      method. The MMG detected with a laser displacement meter, DMMG, was approximated
      with a second-order model, but that detected with an acceleration sensor, AMMG,
      was approximated with a sixth-order model. The natural frequency of the DMMG
      coincided with that in the literature and was close to the lowest natural
      frequency of the AMMG. The highest natural frequency of the AMMG was within the
      range of the resonance frequencies of human soft tissue. The laser displacement
      meter is suitable for the precise identification of the MMG, which has a natural
      frequency of around 3 Hz. The acceleration transducer is suitable for the
      identification of the MMG with natural frequencies of tens of hertz.

PMID- 23129102
TI  - A unique ionic liquid with amphiphilic properties that can form reverse micelles
      and spontaneous unilamellar vesicles.
AB  - Catanionic surfactants: the synthesis of a new surfactant ionic liquid with
      unique properties is described. The formation of reverse micelles in benzene and
      large unilamellar vesicles, formed spontaneously without the help of any
      mechanical of chemistry methods, in water is demonstrated by using dynamic light
      scattering and small-angle X-ray scattering techniques.

PMID- 23129103
TI  - STM-based molecular junction of carbon nano-onion.

PMID- 23129104
TI  - ADAM10 mediates N-cadherin ectodomain shedding during retinal ganglion cell
      differentiation in primary cultured retinal cells from the developing chick
      retina.
AB  - Here, we examined the role of ADAM10 during retinal cell differentiation in
      retinal sections and in vitro cultures of developing chick retinal cells from
      embryonic day 6 (ED6). Immunohistochemistry showed that ADAM10 is abundantly
      expressed in the inner zone of neuroblastic layer at ED5, and it becomes more
      highly expressed in the ganglion cell layer at ED7 and ED9. Western blotting
      confirmed that ADAM10 was expressed as an inactive pro-form that was processed to
      a shorter, active form in control cultured cells, but in cultures treated with an
      ADAM10 inhibitor (GI254023X) and ADAM10-specific siRNA, the level of mature
      ADAM10 decreased. Phase-contrast microscopy showed that long neurite extensions
      were present in untreated cultures 24 h after plating, whereas cultures treated
      with GI254023X showed significant decreases in neurite extension.
      Immunofluorescence staining revealed that there were far fewer differentiated
      ganglion cells in ADAM10 siRNA and GI254023X-treated cultures compared to
      controls, whereas the photoreceptor cells were unaltered. The Pax6 protein was
      more strongly detected in the differentiated ganglion cells of control cultures
      compared to ADAM10 siRNA and GI254023X-treated cultures. N-cadherin ectodomain
      shedding was apparent in control cultures after 24 h, when ganglion cell
      differentiation was observed, but ADAM10 siRNA and GI254023X treatment inhibited
      these processes. In contrast, N-cadherin staining was strongly detected in
      photoreceptor cells regardless of ADAM10 siRNA and GI254023X treatment. Taken
      together, these data indicate that the inhibition of ADAM10 can inhibit Pax6
      expression and N-cadherin ectodomain shedding in retinal cells, possibly
      affecting neurite outgrowth and ganglion cell differentiation.

PMID- 23129105
TI  - Immediate effects of a brief mindfulness-based body scan on patients with chronic
      pain.
AB  - Mindfulness-based stress reduction (MBSR) has benefits for those with chronic
      pain. MBSR typically entails an intensive 8-week intervention. The effects of
      very brief mindfulness interventions are unknown. Among those with chronic pain,
      the immediate effects of a 10 min mindfulness-based body scan were compared with
      a control intervention. Fifty-five adult outpatients were randomly assigned to
      either: (1) mindfulness-based body scan (n = 27) or (2) a reading about natural
      history (control group, n = 28), provided via a 10 min audio-recording.
      Interventions were delivered twice across 24 h; once in the clinic and once in
      participants' 'normal' environment. Immediately before and after listening to the
      recording, participants rated pain severity, pain related distress, perceived
      ability for daily activities, perceived likelihood of pain interfering with
      social relations, and mindfulness. In the clinic, there was a significant
      reduction in ratings for pain related distress and for pain interfering with
      social relations for the body scan group compared with the control group (p =
      0.005; p = 0.036, respectively). In the normal environment none of the ratings
      were significantly different between the groups. These data suggest that, in a
      clinic setting, a brief body scan has immediate benefits for those experiencing
      chronic pain. These benefits need to be confirmed in the field. 

PMID- 23129106
TI  - The transmaxillary endoscopic approach to the orbit.
AB  - OBJECTIVE: In this surgical-anatomical cadaveric study we investigate the
      feasibility of the transmaxillary endoscopic approach to the intraorbital space.
      Anatomical landmarks are defined, the endoscopic view in the orbital space is
      studied and complications that can occur are discussed. METHODS: Nine formalin
      fixed heads were used to study the transmaxillary endoscopic approach to the
      orbit. The approach was used twice on each head (once for each maxilla).
      Therefore, we report our results on 18 transmaxillary intraorbital approaches.
      For better differentiation of anatomical structures, the veins and arteries were
      injected with blue and red plastic respectively in six cadaveric heads. RESULTS:
      The transmaxillary approach enables viewing the inferior intraconal structures
      without endangering the infraorbital nerve and its artery and without diversion
      of the inferior rectus muscle. The optic nerve was visualised more easily through
      the approach medial to the inferior rectus muscle instead of lateral to the
      muscle since the ciliary nerves are in the way in the lateral approach. The
      combination of the approaches medial and lateral to the inferior rectus muscle
      allows very good identification of all important anatomical structures in the
      inferior intraconal space. CONCLUSION: The transmaxillary endoscopic approach to
      the orbit is a useful new approach in the surgical armamentarium for orbital
      lesions. The overview of the inferior part of the orbit is excellent, and the
      lateral part of the optic nerve can be visualised. Careful anatomical dissection
      allows visualisation of important anatomical structures in the orbit without
      damaging nerves or arteries.

PMID- 23129107
TI  - Does atrioventricular reentry tachycardia (AVRT) or atrioventricular nodal
      reentry tachycardia (AVNRT) in children affect their cognitive and emotional
      development?
AB  - The current study sought to assess cognitive and emotional functions among
      children and adolescents with atrioventricular reentry tachycardia (AVRT) and
      atrioventricular nodal reentry tachycardia (AVNRT). 113 patients (62 girls and 51
      boys ages, 9-18 years) scheduled for radiofrequency ablation due to AVRT or AVNRT
      underwent neuropsychologic examination. The study excluded patients who had
      experienced cardiac arrest, congenital heart defects, neurologic disorders, or
      other diseases affecting cognitive or emotional development. Standardized tests
      for examining verbal and visual memory as well as visual-spatial functioning were
      performed. For patients exhibiting deficits in two or more tests, a diagnosis of
      "cognitive deficits" was determined. Levels of anxiety were tested using the
      State-Trait Anxiety Inventory. Cognitive deficits were found in 47.8 % of the
      patients. The age at first arrhythmia attack was related to memory dysfunction.
      The mean age at which the first symptoms occurred was significantly lower for
      patients with deficits (8.3 years) than for patients who had no deficit (10.2
      years) (t = 2.15; p = 0.03). Boys exhibited a significantly higher level of trait
      anxiety than girls (t = 3.42; p = 0.0009). A significant negative correlation was
      found between anxiety and the age at appearance of the first symptoms (r = -0.26;
      p = 0.005). These findings led us to conclude that cognitive and emotional
      developments can be negatively affected by AVNRT and AVRT, particularly if
      tachycardia appears early in life.

PMID- 23129110
TI  - Estimation of sensitivity depending on sojourn time and time spent in preclinical
      state.
AB  - The probability model for periodic screening was extended to provide statistical
      inference for sensitivity depending on sojourn time, in which the sensitivity was
      modeled as a function of time spent in the preclinical state and the sojourn
      time. The likelihood function with the proposed sensitivity model was then
      evaluated with simulated data to check its reliability in terms of the mean
      estimation and the standard error. Simulation results showed that the maximum
      likelihood estimates of the proposed model have little bias and small standard
      errors. The extended probability model was further applied to the Johns Hopkins
      Lung Project data using both maximum likelihood estimation and Bayesian Markov
      chain Monte Carlo.

PMID- 23129109
TI  - Use of purified fibrinogen concentrate for dysfibrinogenemia and importance of
      laboratory fibrinogen activity measurement.
AB  - We report a patient with dysfibrinogenemia treated with purified fibrinogen
      concentrate who had discrepant post-treatment laboratory values. The patient had
      mild bleeding symptoms and was diagnosed with dysfibrinogenemia based on
      fibrinogen activity of 51 mg/dl and antigen of 240 mg/dl. He was treated for an
      adenoidectomy with purified fibrinogen concentrate (RiaSTAP(r)) at a dose of 70
      mg/kg. A discrepancy in post-treatment fibrinogen activity was observed between
      the hospital and reference laboratories. Investigation revealed differences in
      laboratory assay and calibration methods. Fibrinogen concentrate may be a
      treatment option for patients with dysfibrinogenemia, but accurate laboratory
      technique is critical for fibrinogen measurement.

PMID- 23129111
TI  - Live attenuated measles virus vaccine induces apoptosis and promotes tumor
      regression in lung cancer.
AB  - Although the treatment of lung carcinoma has improved, at least 65% of patients
      with this tumor succumb to progressive disease. Measles virus oncolytic therapy
      has been reported to be effective in reducing tumor burden in immunocompetent or
      nude mice; however, its potential to reduce tumor burden in lung carcinoma
      remains to be determined. Herein, we report the potent antitumor effects of a
      live attenuated measles vaccine virus Hu-191 strain (MV) against lung carcinoma.
      Immunocompetent C57BL/6 mice bearing Lewis lung carcinoma (LLC) cells were
      treated with MV (1x104 to 1x106 CCID50/ml) once every other day for 10 days. Our
      results showed that treatment with MV effectively suppressed tumor growth and
      significantly prolonged the survival time of tumor-bearing animals. Histological
      examination revealed that the antitumor effects of MV therapy may result from
      increased induction of apoptosis, tumor necrosis and elevated lymphocyte
      infiltration. Our data suggest that MV, one of the widely used vaccines in China,
      has the ability to inhibit the growth of mouse lung carcinoma and may prove
      useful in the further exploration of the application of this approach in the
      treatment of human advanced lung cancer.

PMID- 23129112
TI  - Expression of ghrelin and leptin during the development of type 2 diabetes
      mellitus in a rat model.
AB  - The aim of this study was to investigate the syste-matic changes in ghrelin and
      leptin expression, as well as their correlation with insulin resistance (IR)
      during the development of type 2 diabetes mellitus (T2DM) in a rat model. T2DM
      was induced in rats fed a high-fat (HF)-diet followed by the intraperitoneal
      injection of low-dose streptozotocin (STZ, 35 mg/kg). Sixty male Sprague-Dawley
      rats were divided into 4 groups: the control, HF-4W (HF diet for 4 weeks), HF-8W
      (HF diet for 8 weeks) and the T2DM group. During the development of T2DM, the
      production of ghrelin in the stomach and leptin in adipose tissue, the blood
      levels of ghrelin and leptin, and the expression of leptin and ghrelin receptors
      (OB-Rb and GHS-R1a) in the hypothalamus were measured by enzyme-linked
      immunosorbent assay (ELISA), radioimmunology assay (RIA), immunohistochemistry
      (IHC) and real-time reverse transcription-polymerase chain reaction (real-time RT
      PCR). IR was assessed using the hyperinsulinemic-euglycemic clamp technique. The
      production of ghrelin in the stomach, the plasma ghrelin levels and the
      expression of GHS-R1a in the hypothalamus were significantly reduced in the HF-4W
      and HF-8W rats compared with the control rats; however, no significant difference
      was found between the HF-8W and T2DM group rats. Comparing the control to the
      T2DM group, the production of leptin in the adipose tissue and the serum leptin
      levels increased, whereas the expression of OB-Rb in the hypothalamus decreased.
      At the same time, the glucose infusion rate (GIR), indicating the insulin
      sensitivity, decreased significantly; GIR positively correlated with plasma
      ghrelin and negatively correlated with serum leptin levels. In conclusion,
      increased leptin levels are associated with obesity and T2DM, while decreased
      ghrelin levels are associated with obesity/IR rather than T2DM. 

PMID- 23129113
TI  - [Correction arthrodesis of the proximal interphalangeal joint with wire cerclage
      for rigid small toe deformities : a prospective study].
AB  - Deformities of the small toes often occur with complex forefoot deformities.
      Proximal interphalangeal joint arthrodesis is a reliable correction procedure for
      rigid flexed proximal interphalangeal joints. The most often performed technique
      by far is K-wire fixation; however, pin tract infections, malrotation due to
      deficient securing of the rotation and irritation of the metatarsophalangeal
      joints are common complications. By using a 0.4 mm wire cerclage an individual
      position of the proximal interphalangeal joint in slight flexion is enabled
      whereby good compression can be achieved and malrotation can be avoided. In 32
      patients with 64 fixed claw or hammer toes such a proximal interphalangeal joint
      arthrodesis was performed. The follow-up time was 2 years. In all cases clinical
      and radiological osteotomy healing occurred 6 weeks postoperatively and there
      were no complications. This technically simple and cost-efficient procedure
      appears to be a good alternative to known proximal interphalangeal joint
      arthrodesis methods.

PMID- 23129114
TI  - Polygonum viviparum L. inhibits the lipopolysaccharide-induced inflammatory
      response in RAW264.7 macrophages through haem oxygenase-1 induction and
      activation of the Nrf2 pathway.
AB  - BACKGROUND: Polygonum viviparum L. (PV) is a member of the family Polygonaceae
      and is widely distributed in high-elevation areas. It is used as a folk remedy to
      treat inflammation-related diseases. This study was focused on the anti
      inflammatory response of PV against lipopolysaccharide (LPS)-induced inflammation
      in RAW264.7 macrophages. RESULTS: Treatment with PV did not cause cytotoxicity at
      0-50 ug mL(-1) in RAW264.7 macrophages, and the IC(50) value was 270 ug mL(-1).
      PV inhibited LPS-stimulated nitric oxide (NO), prostaglandin (PG)E(2) ,
      interleukin (IL)-1beta and tumour necrosis factor (TNF)-alpha release and
      inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 protein expression. In
      addition, PV suppressed the LPS-induced p65 expression of nuclear factor (NF)
      kappaB, which is associated with the inhibition of IkappaB-alpha degradation.
      These results suggest that, among mechanisms of the anti-inflammatory response,
      PV inhibits the production of NO and these cytokines by down-regulating iNOS and
      COX-2 gene expression. Furthermore, PV can induce haem oxygenase (HO)-1 protein
      expression through nuclear factor E2-related factor 2 (Nrf2) activation. A
      specific inhibitor of HO-1, zinc(II) protoporphyrin IX, inhibited the suppression
      of iNOS and COX-2 expression by PV. CONCLUSION: These results suggest that PV
      possesses anti-inflammatory actions in macrophages and works through a novel
      mechanism involving Nrf2 actions and HO-1. Thus PV could be considered for
      application as a potential therapeutic approach for inflammation-associated
      disorders.

PMID- 23129116
TI  - Approaches to studying Arf GAPs in cells: in vitro assay with isolated focal
      adhesions.
AB  - The Arf GAPs are a family of proteins with a common catalytic function of
      hydrolyzing GTP bound to ADP-ribosylation factors (Arf) with proposed cellular
      functions that are diverse (Inoue and Randazzo, 2007; Kahn et al., 2008).
      Understanding the biochemistry of the Arf GAPs is valuable for designing and
      interpreting experiments using standard cell biology techniques described
      elsewhere. The following briefly reviews some common approaches for in vivo
      studies of Arf GAPs and discusses the use of isolated cellular organelles to
      complement in vivo experiments. Detailed protocols for examining the activity of
      Arf GAPs in whole cell lysates and in association with isolated focal adhesions
      are provided.

PMID- 23129115
TI  - Suppression of PTEN transcription by UVA.
AB  - Although ultraviolet A (UVA; 315-400 nm) has different physical and biological
      targets than ultraviolet B (UVB; 280-315 nm), the contribution of UVA to skin
      cancer susceptibility and its molecular basis remain largely unknown. Here we
      show that chronic UVA radiation suppresses phosphatase and tensin homolog (PTEN)
      expression at the mRNA level. Subchronic and acute UVA radiation also
      downregulated PTEN in normal human epidermal keratinocytes, skin culture, and
      mouse skin. At the molecular level, chronic UVA radiation decreased the
      transcriptional activity of the PTEN promoter in a methylation-independent
      manner, whereas it had no effect on the protein stability or mRNA stability of
      PTEN. In contrast, we found that UVA-induced activation of the Ras/ERK/AKT and NF
      kB pathways plays an important role in UV-induced PTEN downregulation. Inhibiting
      extracellular signal-regulated kinases (ERK) or protein pinase B (AKT) increases
      PTEN expression. Our findings may provide unique insights into PTEN
      downregulation as a critical component of UVA's molecular impact during
      keratinocyte transformation.

PMID- 23129117
TI  - Cardiac differentiation of human embryonic stem cells and their assembly into
      engineered heart muscle.
AB  - The advent of pluripotent human embryonic stem cells has created the unique
      opportunity for the development of a wide variety of humanized cellular tools for
      basic research, as well as industrial and clinical applications. It has, however,
      become apparent that embryonic stem cell derivatives in classical monolayer or
      embryoid body culture do not resemble bona fide tissues, mainly because of their
      limited organotypic organization and maturation in these culture formats. This
      shortcoming may be addressed by tissue engineering technologies aiming at the
      provision of a "natural" growth environment to facilitate organotypic tissue
      assembly. In this unit, we provide two harmonized basic protocols for (1) cardiac
      differentiation of human embryonic stem cells under serum-free conditions and (2)
      the assembly of the stem cell-derived cardiomyocytes into engineered heart
      muscle. This protocol can be easily adapted to bioengineer heart muscle also from
      other stem cell-derived cardiomyocytes, including cardiomyocytes from human
      induced pluripotent stem cells.

PMID- 23129118
TI  - Analysis of protein turnover by quantitative SNAP-based pulse-chase imaging.
AB  - Assessment of protein dynamics in living cells is crucial for understanding their
      biological properties and functions. The SNAP-tag, a self labeling suicide
      enzyme, presents a tool with unique features that can be adopted for determining
      protein dynamics in living cells. Here we present detailed protocols for the use
      of SNAP in fluorescent pulse-chase and quench-chase-pulse experiments. These time
      slicing methods provide powerful tools to assay and quantify the fate and
      turnover rate of proteins of different ages. We cover advantages and pitfalls of
      SNAP-tagging in fixed- and live-cell studies and evaluate the recently developed
      fast-acting SNAPf variant. In addition, to facilitate the analysis of protein
      turnover datasets, we present an automated algorithm for spot recognition and
      quantification.

PMID- 23129119
TI  - Quality assessment in pancreatic surgery: what might tomorrow require?
AB  - INTRODUCTION: The Institute of Medicine (IOM) defines healthcare quality across
      six domains: safety, timeliness, effectiveness, patient centeredness, efficiency,
      and equitability. We asked experts in pancreatic surgery (PS) whether improved
      quality metrics are needed, and how they could align to contemporary IOM
      healthcare quality domains. METHODS: We created and distributed a web-based
      survey to pancreatic surgeons. Respondents ranked 62 proposed PS quality metrics
      on level of importance (LoI) and aligned each metric to one or more IOM quality
      domains (multi-domain alignment (MDA)). LoI and MDA scores for a given quality
      metric were averaged together to render a total quality score (TQS) normalized to
      a 100-point scale. RESULTS: One hundred six surgeons (21 %) completed the survey.
      Ninety percent of respondents indicated a definite or probable need for improved
      quality metrics in PS. Metrics related to mortality, to rates and severity of
      complications, and to access to multidisciplinary services had the highest TQS.
      Metrics related to patient satisfaction, costs, and patient demographics had the
      lowest TQS. The least represented IOM domains were equitability, efficiency, and
      patient-centeredness. CONCLUSIONS: Experts in pancreatic surgery have significant
      consensus on 12 proposed metrics of quality that they view as both highly
      important and aligned with more than one IOM healthcare quality domain.

PMID- 23129120
TI  - Laparoscopic total fundoplication for gastroesophageal reflux disease. How I do
      it.
AB  - INTRODUCTION: A laparoscopic fundoplication is considered today the procedure of
      choice for the treatment of gastroesophageal reflux disease (GERD). DISCUSSION:
      Several eponyms are used in the literature to denote different antireflux
      operations: Nissen, Nissen-Rossetti, Toupet, Lind, Guarner, Hill, and Dor. We
      feel that it is more important to focus on the technical elements which make a
      fundoplication effective and long lasting. The type of fundoplication (total vs.
      partial) is tailored to the quality of esophageal peristalsis as documented by
      the preoperative manometry. In the USA, a partial fundoplication is chosen only
      for patients with very impaired or absent esophageal peristalsis. CONCLUSION:
      This article describes the technique of laparoscopic total fundoplication for
      GERD. Partial fundoplication is performed following the same technical elements
      as the total fundoplication. A 240 degrees  to 270 degrees  wrap rather than a
      360 degrees  wrap is performed.

PMID- 23129121
TI  - Female fertility loss and preservation: threats and opportunities.
AB  - BACKGROUND: Ovarian aging and cytotoxic treatments are the most common causes for
      fertility loss in women. With increasing numbers of young female survivors
      following cytotoxic cancer treatments, the issue of fertility preservation has
      assumed greater importance. METHODS: We review the literature on the causes of
      female fertility loss as well as the recent advances in fertility preservation
      options and strategies that might be of interest to oncologists. Currently,
      several methods and techniques exist for fertility preservation of female
      patients with cancer including embryo freezing, ovarian protection techniques,
      oocyte cryopreservation, ovarian tissue cryopreservation followed by
      autotransplantation, and recently in vitro culture of ovarian tissue, follicles,
      and oocytes. Each method or technique has advantages and disadvantages related to
      current success rate, required delay in cancer treatment, sperm requirement, and
      risk of reintroducing cancer cells. RESULTS: To date, embryo freezing is the only
      established method successfully and widely used for fertility preservation of
      female patients with cancer. The other methods are promising but still considered
      experimental. CONCLUSION: Patient awareness, physician knowledge, early
      counseling, costs management, international registry, interdisciplinary networks,
      and research development are necessary to improve the current care in the field
      of female fertility preservation.

PMID- 23129122
TI  - Erlotinib as second-line treatment in patients with advanced non-small-cell lung
      cancer and asymptomatic brain metastases: a phase II study (CTONG-0803).
AB  - BACKGROUND: This phase II, open-label study evaluated the efficacy and safety of
      erlotinib as second-line therapy in non-small-cell lung cancer (NSCLC) patients
      with brain metastases (BM). PATIENTS AND METHODS: Forty-eight patients aged 18-75
      years with Eastern Cooperative Oncology Group performance status 0-2, confirmed
      adenocarcinoma or activating epidermal growth factor receptor (EGFR) mutation
      positive NSCLC, and asymptomatic BM without extracranial progressive disease
      after first-line platinum-doublet chemotherapy were recruited. Treatment
      comprised erlotinib 150 mg/day. The primary end point was progression-free
      survival (PFS) determined by RECIST. RESULTS: The median PFS was 10.1 months [95%
      confidence interval (CI) 7.1-12.3] for intracranial progression and 9.7 months
      (95% CI 2.5-17.8) for intracranial and systemic progression. Patients with EGFR
      mutation-positive disease had significantly longer median PFS versus EGFR wild
      type disease [15.2 months (95% CI 8.3-22.2) versus 4.4 months (95% CI 0.0-11.6);
      P = 0.02]. The median overall survival was 18.9 months (95% CI 14.4-23.4); 6
      month and 1-year survival rates were 85% and 73%, respectively. Overall response
      rate was 58.3%. Most common adverse events were rash (77.1%), paronychia (20.8%),
      hyperbilirubinemia (16.7%), and diarrhea (14.6%); these were predominantly of
      grade 1/2. CONCLUSIONS: Single-agent erlotinib was active and well tolerated in
      NSCLC patients with BM. Further studies are warranted.

PMID- 23129123
TI  - Interim analysis of START: Study in Asia of the combination of TACE
      (transcatheter arterial chemoembolization) with sorafenib in patients with
      hepatocellular carcinoma trial.
AB  - Transarterial chemoembolization (TACE) represents a first-line noncurative
      therapy for hepatocellular carcinoma (HCC). Sorafenib, a multikinase inhibitor,
      has been shown to be effective and safe monotherapy in patients with advanced HCC
      and the current study reports the interim results of a prospective Phase II, open
      label, trial investigating the safety and efficacy of the combination of
      sorafenib and conventional TACE in patients from the Asia-Pacific region with
      intermediate HCC. Patients with histologically or clinically diagnosed HCC were
      treated with conventional TACE followed by sorafenib 4 to 7 days later. TACE was
      performed by selective transarterial chemotherapy in the vessels feeding the
      tumor with an emulsion of lipiodol (5-20 ml) and doxorubicin (30-60 mg) followed
      by embolization with absorbable particles (gel foam). TACE/sorafenib cycles were
      repeated every 6-8 weeks. Primary objectives were to evaluate the safety and
      tolerability, in addition to the efficacy of TACE combined with sorafenib for
      HCC. A total of 147 patients were included in the intention-to-treat analysis and
      received at least one dose of sorafenib. Gastrointestinal AEs were reported by
      62.6% of patients while 57.8% reported skin AEs although most were mild to
      moderate. The mean number of cycles undertaken was 2.1 and 63.3% of patients
      achieved either partial response or stable disease. Clinically, the disease
      control rate was 91.2% while the overall response rate was calculated as 52.4%.
      Our study shows that concurrent sorafenib and TACE therapy is safe and effective
      with no unexpected side effects.

PMID- 23129124
TI  - Identification of volatiles from the secretions and excretions of African wild
      dogs (Lycaon pictus).
AB  - Gas chromatography/mass spectrometry was used to identify 103 organic compounds
      from urine, feces, anal glands, and preputial glands of free-ranging African wild
      dogs, Lycaon pictus. Aliphatic acids were the dominant class of compound in all
      materials. In addition to aliphatic acids, urine contained dimethyl sulfone, 1,3
      propanediol, benzoic acid, 1-methyl-2,4-imidazolidinedione, and squalene as major
      components: feces contained indole and cholesterol; and both contained 2
      piperidone, phenol, 4-methyl phenol, benzeneacetic acid, and benzenepropanoic
      acid and other compounds. Anal gland secretion was particularly rich in
      cholesterol and fatty acids, and preputial gland secretion rich in squalene. A
      large majority of the identified compounds have been reported from other mammals,
      including species sympatric with African wild dogs. Eleven of the African wild
      dog components have not been reported previously from mammals and have not been
      found in sympatric species; one component, 1-methylimidazole-5-carboxaldehyde has
      not been reported previously as a natural product. In the chemical profiles of
      their urine, feces, and anal gland secretion African wild dogs differ markedly
      from other canids.

PMID- 23129125
TI  - The response to selection for broad male response to female sex pheromone and its
      implications for divergence in close-range mating behavior in the European corn
      borer moth, Ostrinia nubilalis.
AB  - Coordinated sexual communication systems, seen in many species of moths, are
      hypothesized to be under strong stabilizing natural selection. Stabilized
      communication systems should be resistant to change, but there are examples of
      species/populations that show great diversification. A possible solution is that
      it is directional sexual selection on variation in male response that drives
      evolution. We tested a component of this model by asking whether 'rare' males
      (ca. 5 % of all males in a population) of the European corn borer moth (ECB),
      Ostrinia nubilalis, that respond to the sex pheromones of both ECB and a
      different Ostrinia species (O. furnacalis, the Asian corn borer, ACB), might play
      an important role in diversification. We specifically tested, via artificial
      selection, whether this broad male response has an evolvable genetic component.
      We increased the frequency of broad male response from 5 to 70 % in 19
      generations, showing that broad-responding males could be important for the
      evolution of novel communication systems in ECB. We did not find a broader range
      of mating acceptance of broad males by females of the base population, however,
      suggesting that broad response would be unlikely to increase in frequency without
      the involvement of other factors. However, we found that ECB selection-line
      females accepted a broader range of courting males, including those of ACB, than
      did females of the base population. Thus, a genetic correlation exists between
      broad, long-range response to female sex pheromone and the breadth of female
      acceptance of males at close range. These results are discussed in the context of
      evolution of novel communication systems in Ostrinia.

PMID- 23129126
TI  - Synthesis, structure, and reactivity of a monomeric iminoalane.

PMID- 23129127
TI  - Synthesis and network-like self-assembly of porphyrin-polyselenophene complexes.
AB  - A hexagonal network structure fabricated by self-assembly of a branched
      conjugated polymer with a porphyrin core and P3HT or P3HS arms is presented (see
      picture). Polymer symmetry is very important to the network structure formation
      probably due to the different viscosities in linear and branched polymers.

PMID- 23129128
TI  - Kallikrein-binding protein inhibits LPS-induced TNF-alpha by upregulating SOCS3
      expression.
AB  - Kallikrein-binding protein (KBP) was previously identified as a serpin family
      member with specific inhibitory effect on tissue kallikrein and angiogenesis,
      while there is little knowledge about the effects on inflammation. The aim of
      this study is to investigate whether KBP can suppress LPS-induced inflammatory
      process. Our results showed that both recombinant KBP and KBP overexpression
      inhibited LPS-stimulated TNF-alpha transcription and translation in macrophage
      cell line RAW264.7 and primary macrophages. Furthermore, KBP treatment protected
      mice from endotoxin shock and repressed serum TNF-alpha production, increasing
      survival rate of mice from 10% to 50% when compared to LPS alone. Moreover, qPCR
      and Western blot analysis demonstrated that both suppressor of cytokine signaling
      3 (SOCS3) transcription and translation were induced by KBP treatment in the
      present of LPS. RNA interference assay and luciferase assay showed that SOCS3 was
      responsible for the down-regulation of TNF-alpha by KBP, rather than NF-kappaB
      subunit p65 and beta-catenin. Therefore, we demonstrated that KBP suppressed LPS
      induced TNF-alpha production via upregulating SOCS3 expression. These results
      present the protective effects of KBP on LPS-induced inflammation and provide
      novel information for the anti-inflammation mechanism.

PMID- 23129129
TI  - Genotypic characterization of dengue virus strains circulating during 2007-2009
      in New Delhi.
AB  - Dengue is an important arboviral disease of tropical and subtropical regions,
      with significant morbidity and mortality. Dengue virus is antigenically
      classified into four serotypes, which are further classified into 4-5 genotypes
      based on their genetic diversity. Since genotypes vary in their virulence, their
      detection and analysis of spatial and temporal transition are essential. We
      utilized sequence information from the E-NS1 gene region for molecular and
      phylogenetic characterization of dengue viruses isolated from dengue patients
      between 2007 and 2009. All four serotypes and multiple genotypes were detected,
      with predominance and emergence of DENV-1 genotype V. Phylogenetic analysis
      revealed the emergence of DENV-1 genotype V from India for the first time, which
      has replaced the earlier circulating genotype III and genotype I. The circulation
      of multiple genotypes and genotype replacement is critical, since genotypes vary
      in their virulence, and this should be a point of concern for healthcare
      agencies.

PMID- 23129130
TI  - Detection and sequencing of defective viral genomes in C6/36 cells persistently
      infected with dengue virus 2.
AB  - Dengue virus is the most important arbovirus that affects humans, and it can
      establish persistent infections, especially in insect-derived cell cultures.
      Defective viral genomes have been implicated in the establishment and maintenance
      of persistent infections with several flaviviruses; however, there exists almost
      no information concerning defective dengue virus genomes. Here, we report the
      detection of defective dengue 2 virus genomes in persistently infected mosquito
      C6/36 cells. The defective viral genomes were detected at a low ratio compared
      with the wild-type genome. Deletions of approximately 147 residues (222-368) were
      found in the E protein, and these mainly affected domain III (73 %) of the
      protein; deletions of approximately 153 residues (4-156) and 228 residues (597
      825) were found in the methyltransferase and polymerase domains, respectively, of
      the NS5 protein. The truncated versions of NS5 could be detected by western blot
      only in the protein extracts derived from persistently infected cells.

PMID- 23129131
TI  - Characterization and whole genome sequences of the Rhodococcus bacteriophages
      RGL3 and RER2.
AB  - We report here the isolation and genome sequences of two novel phages, lytic for
      Rhodococcus and Nocardia species. Named RER2 and RGL3, both are members of the
      family Siphoviridae, and each possesses a novel genome of 46,586 bp and 48,072
      bp, respectively. RER2 and RGL3 phages share a modular genome organization, as
      seen in other sequenced Siphoviridae phage genomes, and appear to share a common
      evolutionary origin. The genomes of these phages share no similarity with other
      Rhodococcus or Nocardia phages but are related to Mycobacterium phages. The data
      presented here extend our understanding of Rhodococcus phage genomics.

PMID- 23129132
TI  - Genomic sequence of an infectious bursal disease virus isolate from Zambia:
      classical attenuated segment B reassortment in nature with existing very virulent
      segment A.
AB  - We determined the complete nucleotide sequence of an infectious bursal disease
      (IBD) virus (IBDV) isolate (designated KZC-104) from a confirmed IBD outbreak in
      Lusaka in 2004. The genome consisted of 3,074 and 2,651 nucleotides in the coding
      regions of segments A and B, respectively. Alignment of both nucleotide and
      deduced amino acid sequences and phylogenetic analysis revealed that the genome
      segment A of KZC-104 was derived from a very virulent (VV) strain, whereas its
      segment B was derived from a classical attenuated strain. On BLAST search, the
      full-length segment A and B sequences showed 98 % nucleotide sequence identity to
      the VV strain D6948 and 99.8 % nucleotide sequence identity to the classical
      attenuated strain D78. This is a unique IBDV reassortant strain that has emerged
      in nature, involving segment B of a cell-culture-adapted attenuated vaccine.

PMID- 23129133
TI  - Pretreatment, psychological, and behavioral predictors of weight outcomes among
      lifestyle intervention participants in the Diabetes Prevention Program (DPP).
AB  - OBJECTIVE: To identify the most important pretreatment characteristics and
      changes in psychological and behavioral factors that predict weight outcomes in
      the Diabetes Prevention Program (DPP). RESEARCH DESIGN AND METHODS: Approximately
      25% of DPP lifestyle intervention participants (n = 274) completed questionnaires
      to assess weight history and psychological and behavioral factors at baseline and
      6 months after completion of the 16-session core curriculum. The change in
      variables from baseline to 6 months was assessed with t tests. Multivariate
      models using hierarchical logistic regression assessed the association of weight
      outcomes at end of study with each demographic, weight loss history,
      psychological, and behavioral factor. RESULTS: At end of study, 40.5% had
      achieved the DPP 7% weight loss goal. Several baseline measures (older age, race,
      older age when first overweight, fewer self-implemented weight loss attempts,
      greater exercise self-efficacy, greater dietary restraint, fewer fat-related
      dietary behaviors, more sedentary activity level) were independent predictors of
      successful end-of-study weight loss with the DPP lifestyle program. The DPP core
      curriculum resulted in significant improvements in many psychological and
      behavioral targets. Changes in low-fat diet self-efficacy and dietary restraint
      skills predicted better long-term weight loss, and the association of low-fat
      diet self-efficacy with weight outcomes was explained by dietary behaviors.
      CONCLUSIONS: Health care providers who translate the DPP lifestyle intervention
      should be aware of pretreatment characteristics that may hamper or enhance weight
      loss, consider prioritizing strategies to improve low-fat diet self-efficacy and
      dietary restraint skills, and examine whether taking these actions improves
      weight loss outcomes.

PMID- 23129134
TI  - Branched-chain and aromatic amino acids are predictors of insulin resistance in
      young adults.
AB  - OBJECTIVE: Branched-chain and aromatic amino acids are associated with the risk
      for future type 2 diabetes; however, the underlying mechanisms remain elusive. We
      tested whether amino acids predict insulin resistance index in healthy young
      adults. RESEARCH DESIGN AND METHODS: Circulating isoleucine, leucine, valine,
      phenylalanine, tyrosine, and six additional amino acids were quantified in 1,680
      individuals from the population-based Cardiovascular Risk in Young Finns Study
      (baseline age 32 +/- 5 years; 54% women). Insulin resistance was estimated by
      homeostasis model assessment (HOMA) at baseline and 6-year follow-up. Amino acid
      associations with HOMA of insulin resistance (HOMA-IR) and glucose were assessed
      using regression models adjusted for established risk factors. We further
      examined whether amino acid profiling could augment risk assessment of insulin
      resistance (defined as 6-year HOMA-IR >90th percentile) in early adulthood.
      RESULTS: Isoleucine, leucine, valine, phenylalanine, and tyrosine were associated
      with HOMA-IR at baseline and for men at 6-year follow-up, while for women only
      leucine, valine, and phenylalanine predicted 6-year HOMA-IR (P < 0.05). None of
      the other amino acids were prospectively associated with HOMA-IR. The sum of
      branched-chain and aromatic amino acid concentrations was associated with 6-year
      insulin resistance for men (odds ratio 2.09 [95% CI 1.38-3.17]; P = 0.0005);
      however, including the amino acid score in prediction models did not improve risk
      discrimination. CONCLUSIONS: Branched-chain and aromatic amino acids are markers
      of the development of insulin resistance in young, normoglycemic adults, with
      most pronounced associations for men. These findings suggest that the association
      of branched-chain and aromatic amino acids with the risk for future diabetes is
      at least partly mediated through insulin resistance.

PMID- 23129135
TI  - Carotid-femoral pulse wave velocity is associated with cerebral white matter
      lesions in type 2 diabetes.
AB  - OBJECTIVE: Patients with type 2 diabetes have a high incidence of cardiovascular
      events including stroke. Increased arterial stiffness (AS) predicts
      cardiovascular events in the general population. Cerebral white matter lesions
      (WMLs) are associated with an increased risk of stroke. It is unknown whether AS
      in patients with type 2 diabetes is associated with WMLs. RESEARCH DESIGN AND
      METHODS: We examined 89 patients recently diagnosed with type 2 diabetes (<5
      years) and 89 sex- and age-matched controls. AS was assessed with carotid-femoral
      pulse wave velocity (PWV). WMLs were identified using magnetic resonance imaging
      and graded qualitatively with the Breteler scale (no/slight changes = 0, moderate
      changes = 1, severe changes = 2) and semiquantitatively. RESULTS: The diabetic
      population had excellent glycemic control (HbA(1c), 6.5% [6.2-6.8]; median
      [interquartile range {IQR}]) and had, compared with the controls, lower office
      blood pressure (BP) (127 +/- 12/79 +/- 8 vs. 132 +/- 14/84 +/- 10 mmHg) and total
      cholesterol (4.3[3.9-4.7] vs. 5.6 [5.1-6.4]; mmol/L; median [IQR]), (P < 0.01 for
      all). Despite this, PWV was higher in the patients with diabetes compared with
      controls (9.3 +/- 2.0 vs. 8.0 +/- 1.6 m/s; P < 0.0001). PWV was associated with
      Breteler score (OR 1.36 [95% CI 1.17-1.58]; P < 0.001) and WML volume (OR 1.32
      [95% CI 1.16-1.51]; P < 0.001) per 1 m/s increase in PWV. These associations
      remained significant when adjusted for age, sex, diabetes, 24-h mean arterial BP,
      BMI, heart rate, and use of antihypertensives and statins (Breteler score: OR
      1.28 [95% CI 1.03-1.60]; P < 0.05 and WML volume: OR 1.30 [95% CI 1.06-1.58]; P <
      0.05). CONCLUSIONS: PWV was higher among patients with well-controlled type 2
      diabetes compared with controls and was independently associated with WMLs. PWV
      may represent a clinically relevant parameter in the evaluation of
      cerebrovascular disease risk in type 2 diabetes.

PMID- 23129136
TI  - The phylogenetic structure of microbial biofilms and free-living bacteria in a
      small stream.
AB  - The phylogenetic composition, bacterial biomass, and biovolume of both planktonic
      and biofilm communities were studied in a low-order Bystrice stream near Olomouc
      City, in the Czech Republic. The aim of the study was to compare the microbial
      communities colonizing different biofilm substrata (stream aggregates, stream
      sediment, underwater tree roots, stream stones, and aquatic macrophytes) to those
      of free-living bacteria. The phylogenetic composition was analyzed using
      fluorescence in situ hybridization for main phylogenetic groups. All phylogenetic
      groups studied were detected in all sample types. The stream stone was the
      substratum where nearly all phylogenetic groups were the most abundant, while the
      lowest proportion to the DAPI-stained cells was found for free-living bacteria.
      The probe specific for the domain Bacteria detected 20.6 to 45.8 % of DAPI
      stained cells while the probe specific for the domain Archaea detected 4.3 to
      17.9 %. The most abundant group of Proteobacteria was Alphaproteobacteria with a
      mean of 14.2 %, and the least abundant was Betaproteobacteria with a mean of 11.4
      %. The average value of the Cytophaga-Flavobacteria group was 10.5 %. Total cell
      numbers and bacterial biomass were highest in sediment and root biofilm. The
      value of cell biovolume was highest in stone biofilm and lowest in sediment.
      Overall, this study revealed relevant differences in phylogenetic composition,
      bacterial biomass, and biovolume between different stream biofilms and free
      living bacteria.

PMID- 23129137
TI  - Progression-free survival of two cases of high-risk neuroblastoma with
      refractory/relapsed disease following surgery alone.
AB  - Outcome for the vast majority of high-risk neuroblastoma patients with refractory
      or relapsed disease is dismal. We report two high-risk patients who remain
      progression-free for more than 113 and 18 months following the diagnosis of
      refractory/relapsed disease who were treated with surgery alone. Complete
      resolution of a refractory thoracic mass and relapsed liver nodules was observed
      in one patient. The refractory/relapsed disease in the second patient has
      remained stable. In both cases, the tumor showed histologic evidence of
      neuroblastoma maturation. These cases demonstrate that refractory/relapsed
      neuroblastoma is clinically heterogeneous and highlight the need for better
      biomarkers to optimize patient care.

PMID- 23129138
TI  - Memory and mnemonics.

PMID- 23129139
TI  - Concomitant occurrence of hypohyperdontia in a patient with Marfan syndrome: a
      review of the literature and report of a case.
AB  - Marfan syndrome is an autosomal dominant genetic disorder of connective tissue
      origin that can affect multiple organs. Various oral manifestations have been
      associated with this syndrome. Hypohyperdontia is a condition of mixed numeric
      variations that presents a combination of hypodontia with hyperdontia within a
      single human dentition. The purpose of this paper is to report a case of Marfan
      syndrome with a concomitant occurrence of hypohyperdontia. A narrative review was
      also included to describe the other syndromes that had been associated with
      concomitant hypohyperdontia.

PMID- 23129140
TI  - Aide memoires in oral diagnosis: mnemonics and acronyms (the Scully system).
AB  - This paper highlights some mnemonics and acronyms relevant to orofacial disease.

PMID- 23129141
TI  - Antibacterial action of calcium hydroxide vehicles and calcium hydroxide pastes.
AB  - AIM: To evaluate the in vitro action of vehicles alone and with calcium hydroxide
      against different bacterial species. METHODS: Agar plates were inoculated with
      the microbial suspensions, and wells were made and filled with the calcium
      hydroxide pastes and the vehicles used to prepare the pastes. The zones of
      inhibited bacterial growth were recorded, and the resulting measurements were
      statistically analyzed. RESULTS: Enterococcus faecalis was the most resistant
      microorganism to all medicaments. Calcium hydroxide + p-monochlorophenol; calcium
      hydroxide + p-monochlorophenol-propylene glycol pastes; and p-monochlorophenol, p
      monochlorophenol-propylene glycol, and chlorhexidine gluconate gel alone showed
      the largest zones of inhibition against all the tested microorganisms.
      CONCLUSIONS: The vehicle used to prepare the calcium hydroxide paste might
      contribute to its antibacterial action. Chlorhexidine gluconate gel used alone,
      and camphorated p-monochlorophenol and camphorated p-monochlorophenol-propylene
      glycol as vehicles of calcium hydroxide, could be recommended, in an
      antimicrobial sense.

PMID- 23129142
TI  - Comparative in vitro antibacterial activity of six root canal sealers against
      Enterococcus faecalis and Proteus vulgaris.
AB  - AIM: To evaluate the antimicrobial properties of six endodontic sealers in unset
      and set states against Enterococcus faecalis and Proteus vulgaris. METHODS: Six
      endodontic sealers were investigated in the unset and set state against
      Enterococcus feacalis and Proteus vulgaris using agar diffusion and direct
      contact tests. RESULTS: The mean inhibition zones for agar diffusion tests with
      Enterococcus feacalis were 19 mm for AH-26, 11 mm for TopSeal and Roth 601, 1 mm
      for AH-Plus, and 0 mm for GuttaFlow and EndoREZ (Kruskal-Wallis, P < 0.001). The
      mean inhibition zones with Proteus vulgaris were 24 mm for Roth 601, 19 mm for
      TopSeal, 17 mm for AH-Plus, 16 mm for AH-26, and 0 mm for GuttaFlow and EndoREZ
      (Kruskal-Wallis, P < 0.001). Direct contact tests showed inhibition of both
      Enterococcus feacalis and Proteus vulgaris with AH-Plus, TopSeal, Roth 601, and
      AH-26 in the unset state. Only Roth 601 in the set state affected both the log
      and the stationary phase of Proteus vulgaris (logistic regression P < 0.001).
      CONCLUSIONS: With the exception of Roth 601, which retained its antimicrobial
      activity, the AH-Plus, TopSeal, and AH-26 sealers all demonstrated antimicrobial
      properties against Enterococcus feacalis and Proteus vulgaris that diminished
      when set. TopSeal significantly affected Enterococcus feacalis when compared with
      AH-Plus. GuttaFlow and EndoREZ expressed no antimicrobial activity.

PMID- 23129143
TI  - Factors affecting oral malodor in periodontitis and gingivitis patients.
AB  - AIM: To examine the associations between oral health status, the presence of N
      benzoyl-DL-arginine-2-naphthylamide-positive bacteria, and oral malodor in
      periodontal patients. METHODS: A total of 137 periodontitis and 80 gingivitis
      patients were included in the study. Oral malodor was measured by an organoleptic
      test and the OralChroma. An oral examination was conducted, including the
      assessment of decayed teeth, periodontal status, and tongue coating. The presence
      of N-benzoyl-DL-arginine-2-naphthylamide-positive bacteria in the subgingiva,
      tongue coating, and saliva was evaluated by the N-benzoyl-DL-arginine-2
      naphthylamide test. RESULTS: In the periodontitis group, oral malodor was
      significantly correlated with decayed teeth, periodontal parameters, and tongue
      coating. Among the N-benzoyl-DL-arginine-2-naphthylamide test parameters, the
      highest correlation of oral malodor was found with N-benzoyl-DL-arginine-2
      naphthylamide subgingiva, followed by N-benzoyl-DL-arginine-2-naphthylamide
      tongue coating and N-benzoyl-DL-arginine-2-naphthylamide saliva. In the
      gingivitis group, oral malodor was significantly correlated with the plaque
      index, bleeding on probing, and tongue coating. Among the N-benzoyl-DL-arginine-2
      naphthylamide test parameters, the highest correlation of oral malodor was found
      with N-benzoyl-DL-arginine-2-naphthylamide tongue coating, followed by N-benzoyl
      DL-arginine-2-naphthylamide saliva and N-benzoyl-DL-arginine-2-naphthylamide
      subgingiva. CONCLUSION: Dental plaque, bleeding on probing, tongue coating, and N
      benzoyl-DL-arginine-2-naphthylamide-positive bacteria contribute to oral malodor,
      but with different degrees in periodontitis and gingivitis patients.

PMID- 23129144
TI  - Influence of cigarette smoking on blood and salivary super oxide dismutase levels
      among smokers and non-smokers.
AB  - AIM: To determine the influence of smoking on the blood and salivary superoxide
      dismutase levels among smokers, and to demonstrate the significance in
      alterations in the levels of superoxide dismutase in association with patient
      age, periodontal disease status, and duration and smoking frequency. METHODS:
      Sixty healthy male patients (aged 20-60 years) constituted the target population.
      Blood and saliva samples were collected, and the periodontal index was measured
      using a Community Periodontal Index probe. Blood and salivary superoxide
      dismutase levels were calculated with the reagents prepared, and values were
      measured in a UV spectrophotometer. RESULTS: There was a significant decrease in
      mean superoxide dismutase levels with an increase in age and smoking duration and
      frequency (0.23-0.05 U/mL). There was a range of 0.31-0.06 U/mL variation in the
      mean superoxide dismutase levels as the periodontal disease condition
      deteriorated. CONCLUSIONS: There was a significant reduction in the superoxide
      dismutase levels in the blood and saliva of smokers with increased duration and
      frequency of smoking, and as the periodontal disease condition worsened. Thus,
      this study emphasizes the importance of saliva as an easy, non-invasive procedure
      in the diagnosis of patients who are more prone to precancerous lesions and
      conditions, and its importance in patient education and motivation programs for
      smoking cessation.

PMID- 23129145
TI  - Plagiarism and scientific writing: a personal commentary.
AB  - There have been a number of papers that have addressed the issue of plagiarism.
      Nevertheless, the charges of plagiarism usually merit little attention with
      experts, because it is still not clear what sort of copying actually constitutes
      plagiarism. Another problem that eludes consensus is whether plagiarism was
      committed with or without intention. This paper discusses certain issues relating
      to plagiarism and differentiates between intentional and unintentional forms of
      plagiarism.

PMID- 23129146
TI  - R4 regulators of G protein signaling (RGS) identify an ancient MHC-linked synteny
      group.
AB  - Regulators of G protein signaling (RGS) are key regulators of G protein
      signaling. RGS proteins of the R4 RGS group are composed of a mere RGS domain and
      are mainly involved in immune response modulation. In both human and mouse, most
      genes encoding the R4 RGS proteins are located in the same region of chromosome
      1. We show here that the RGS1/RGS16 neighborhood constitutes a synteny group well
      conserved across tetrapods and closely linked to the MHC paralogon of chromosome
      1. Genes located in the RGS1/RGS16 region have paralogs close to the MHC on
      chromosome 6 or close to the other MHC paralogons. In amphioxus, a
      cephalochordate, these genes possess orthologs that are located in the same
      scaffolds as a number of markers defining the proto-MHC in this species (Abi
      Rached et al., Nat Genet 31:100-115, 2002). We therefore propose that the
      RGS1/RGS16 region provides useful markers to investigate the origins and the
      evolution of the MHC. In addition, we show that some genes of the region appear
      to have immune functions not only in human, but also in Xenopus.

PMID- 23129147
TI  - Antineoplastic activity of a nutrient mixture in Y-79 malignant retinoblastoma
      cells.
AB  - Retinoblastoma is one of the most common ocular malignancies in children under
      the age of six. Occasionally, retinoblastoma metastasizes to extraocular organs
      including the bone, lung and brain. Left untreated, retinoblastoma is fatal. At
      present, there is no effective treatment for metastatic retinoblastoma. We
      investigated the antineoplastic activity of a nutrient mixture (NM) (lysine,
      proline, ascorbic acid and green tea extract) at concentrations of 10, 50, 100,
      500 and 1,000 ug/ml in triplicate at each dose in the human malignant
      retinoblastoma Y-79 cell line. The parameters used were cell proliferation,
      expression of matrix metalloproteinases (MMPs), invasion through Matrigel,
      morphology and apoptosis. Cell viability was assessed by trypan blue dye
      exclusion test. Invasion was evaluated through Matrigel and MMP activity by
      gelatinase zymography. H&E staining for morphological cell alterations and
      apoptotic studies using the Live Green Poly Caspase Detection kit were also
      conducted. The nutrient mixture at 10-100 ug/ml demonstrated approximately 25%
      toxicity towards Y-79 retinoblastoma cells and significant toxicity at 500 and
      1,000 ug/ml. The Y-79 cells secreted only MMP-2 as demonstrated by zymography;
      the nutrient mixture had no effect on MMP-2 expression up to 100 ug/ml, but
      completely blocked it at 500 ug/ml. Importantly, Y-79 retinoblastoma cells were
      not invasive through Matrigel. H&E staining showed cell morphological changes
      related to apoptosis, which was confirmed using the Live Green Poly Caspase
      Detection kit. Our results suggest that this nutrient mixture, which inhibited
      cell proliferation, expression of MMP-2 and induced apoptosis, may be a candidate
      for further exploration for its therapeutic potential in metastatic
      retinoblastoma.

PMID- 23129148
TI  - High-dose magnesium sulfate infusion protocol for status asthmaticus: a safety
      and pharmacokinetics cohort study.
AB  - PURPOSE: To assess the safety and pharmacokinetics of high-dose magnesium sulfate
      (MgSO(4)) infusion in pediatric patients with status asthmaticus. METHODS: A
      prospective cohort study within a 20-bed pediatric intensive care unit in an
      academic community hospital. Patients 2-18 years of age admitted with status
      asthmaticus between 10/2009 and 8/2010 were included in the study. All patients
      received standard therapy for asthma, while the treatment group received an
      intravenous magnesium sulfate bolus of 50-75 mg/kg (0.2-0.3 mmol/kg) followed by
      40 mg/kg/h (0.16 mmol/kg/h) for 4 h. Patients were monitored for
      cardiorespiratory complications. The treatment group underwent four blood draws
      to assess pharmacokinetic parameters. RESULTS: Nineteen patients were in the
      treatment group and 38 patients in the control group after exclusion criteria and
      consenting were completed. No clinically significant differences were found
      between groups. There were no interventions or discontinuations of MgSO(4) due to
      adverse events. In the treatment group, three patients had mild infusion-related
      reactions. Heart rate and respiratory rate were statistically significantly lower
      in the magnesium treatment group. CONCLUSIONS: The continuous infusions of
      MgSO(4) were safe at the studied doses and maintained serum magnesium (SrMg) and
      ionized magnesium levels similar to levels required to produce smooth muscle
      relaxation in other clinical settings. Further studies are needed to investigate
      the efficacy of high-dose continuous MgSO(4) infusion as an adjunctive treatment
      for severe asthma treatment and determine the SrMg level required to maintain
      airway smooth muscle relaxation.

PMID- 23129151
TI  - Enhancing the alkaline hydrogen evolution reaction activity through the
      bifunctionality of Ni(OH)2/metal catalysts.
AB  - Active in alkaline environment: The activity of nickel, silver, and copper
      catalysts for the electrochemical transformation of water to molecular hydrogen
      in alkaline solutions was enhanced by modification of the metal surfaces by
      Ni(OH)(2) (see picture; I = current density and eta = overpotential). The
      hydrogen evolution reaction rate on a Ni electrode modified by Ni(OH)(2)
      nanoclusters is about four times higher than on a bare Ni surface.

PMID- 23129152
TI  - Cryopreservation and thawing of cells.
AB  - Successful cryopreservation of cells requires not only that the cells be handled
      in a proper fashion for harvesting with equipment in place to ensure consistency,
      reproducibility, and sterility, but also that a correct choice and amount of
      cryoprotective agent is added. In general, a controlled freezing rate of 1
      degrees C/min is necessary to retain optimal viability of the recovered cells.
      There are many variations of cell freezing methods in use, including costly
      electronically regulated control rate freezers, unstandardized, passive isopropyl
      alcohol freezing containers, and crude rudimentary devices constructed from
      Styrofoam boxes or paper insulation. However, for the freezing and recovery of
      cell lines, primary cells, and stem cell cultures, the protocol described in this
      unit is simple, reproducible, and successful. Not only does it eliminate the need
      for isopropanol, as well as the costs and hazards associated with its use and
      disposal, but it provides a uniform method with improved cell viability and
      recovery.

PMID- 23129153
TI  - Measurement of phagocytosis, phagosome acidification, and intracellular killing
      of Staphylococcus aureus.
AB  - Phagocytes are an important part of host defense, playing a critical role in
      innate immune responses against pathogens and in the initiation of adaptive
      immunity. One of the main characteristics of these cells is their ability to
      recognize and internalize invading microorganisms into a phagosome. The
      internalized microbe is rapidly delivered into a mature phagolysosome where it is
      killed and degraded. However, numerous pathogens have evolved complex mechanisms
      to manipulate these intracellular organelles to establish a survival niche. Here,
      we describe several methods to assess important properties of phagosomes in
      macrophages, such as phagocytosis, acidification of the phagosome contents during
      the maturation process, and the ability of phagosomes to inactivate and kill
      pathogens. Phagocytosis and phagosome acidification assays are FACS-based assays
      where labeled bacteria are used as probes to monitor internalization into a
      phagosome and to detect the pH of the phagosome environment. The killing assay is
      based on the counting of bacterial colonies after recovery of internalized
      bacteria from macrophages.

PMID- 23129154
TI  - Isolation of mouse lymphocytes from small intestine tissues.
AB  - The isolation of lymphocytes and other hematopoietic-derived cells from small
      intestinal tissues has become increasingly relevant to immunology over the last
      decade. It is also becoming increasingly clear that the impact of local immunity
      at the mucosal barrier of the intestine has a profound impact on immune responses
      at distant sites, bringing a new cadre of immunologists to the mucosal frontier.
      Furthermore, the ability to experimentally manipulate smaller and smaller
      populations of immune cells has become technologically feasible and in some cases
      routine. The expanding importance of mucosal immunology coupled with increased
      technical capabilities requires a standard for experimentally obtaining uniform
      and consistent cells from the intestinal mucosa. Therefore, it is important to
      isolate immune cells that are highly viable and minimally manipulated to maximize
      cellular yields while maintaining acceptable time constraints.

PMID- 23129156
TI  - Identification of B cell and T cell epitopes using synthetic peptide
      combinatorial libraries.
AB  - This unit presents a combinatorial library method that consists of the synthesis
      and screening of mixture-based synthetic combinatorial libraries of peptide
      molecules. The protocols employ peptide libraries to identify peptides recognized
      by MAbs and T cells. The first protocol uses a positional scanning peptide
      library made up of hexapeptides to identify antigenic determinants recognized by
      MAbs. The 120 mixtures in the hexapeptide library are tested for their inhibitory
      activity in a competitive ELISA. The second protocol uses a decapeptide library
      to identify T cell peptide ligands. The 200 mixtures of the decapeptide library
      are tested for their ability to induce T cell activation. Support protocols cover
      optimization of the assay conditions for each MAb or T cell, to achieve the best
      level of sensitivity and reproducibility, and preparation of a hexapeptide
      library, along with deconvolution approaches.

PMID- 23129155
TI  - Isolation and generation of human dendritic cells.
AB  - Dendritic cells are highly specialized antigen-presenting cells (APC), which may
      be isolated or generated from human blood mononuclear cells. Although mature
      blood dendritic cells normally represent ~0.2% of human blood mononuclear cells,
      their frequency can be greatly increased using the cell enrichment methods
      described in this unit. More highly purified dendritic cell preparations can be
      obtained from these populations by sorting of fluorescence-labeled cells.
      Alternatively, dendritic cells can be generated from monocytes by culture with
      the appropriate cytokines, as described here. In addition, a negative selection
      approach is provided that may be employed to generate cell preparations that have
      been depleted of dendritic cells to be used for comparison in functional studies.

PMID- 23129157
TI  - Blue LED inhibits the growth of Porphyromonas gingivalis by suppressing the
      expression of genes associated with DNA replication and cell division.
AB  - BACKGROUND AND OBJECTIVES: Blue light has been employed or investigated in both
      the medical and dental fields. Many studies have so far been reported a
      bactericidal effect of blue light emitting diodes (LED). However, it is still
      unclear whether exposure to blue LED kills or inhibits the growth of bacteria. We
      therefore investigated the effect of blue LED irradiation on the growth of
      Porphyromonas gingivalis compared with the effects of red LED. MATERIALS AND
      METHODS: P. gingivalis cell suspensions were irradiated with blue or red LED (135
      J/cm2) anaerobically, incubated for various lengths of time, and then the total
      RNAs were isolated. The RNA degradation and gene expression levels of stress
      related proteins in blue or red LED-irradiated samples were examined using the
      RNA integrity number (RIN) and RT-PCR, respectively. Quantitative RT-PCR was done
      to investigate the gene expression profiles associated with chromosome
      replication and cell division. RESULTS: Exposure to blue LED delayed the growth
      of P. gingivalis, while red LED did not. The RIN value indicated no RNA
      degradation in either the blue or red LED-irradiated samples. In addition, the
      gene expression levels of stress-related molecules remained either constant or
      increased 15 minutes after the blue LED irradiation compared to that before
      irradiation, thus suggesting that blue LED may not kill P. gingivalis cells.
      However, the blue LED irradiation did lead to a remarkably decreased expression
      of genes associated with chromosomal DNA replication and cell division after 5
      minutes; exposure to the red LED did not. CONCLUSION: The inhibition of the
      growth of P. gingivalis by blue LED may therefore be induced not by a
      bactericidal effect, but instead due to a bacteriostatic effect mediated by the
      suppression of the genes associated with chromosomal DNA replication and cell
      division at the transcriptional level.

PMID- 23129158
TI  - Getting to better prescription drug information.

PMID- 23129159
TI  - Receipt of high risk medications among elderly enrollees in Medicare Advantage
      plans.
AB  - BACKGROUND: Since 2005, the Centers for Medicare and Medicaid Services (CMS) has
      required all Medicare Advantage (MA) plans to report prescribing rates of high
      risk medications (HRM). OBJECTIVE: To determine predictors of receipt of HRMs, as
      defined by the National Committee for Quality Assurance's "Drugs to Avoid in the
      Elderly" quality indicator, in a national sample of MA enrollees. DESIGN AND
      PARTICIPANTS: Retrospective analysis of Healthcare Effectiveness Data and
      Information Set (HEDIS) data for 6,204,824 enrollees, aged 65 years or older,
      enrolled in 415 MA plans in 2009. To identify predictors of HRM use, we fit
      generalized linear models and modeled outcomes on the risk-difference scale. MAIN
      OUTCOME MEASURES: Receipt or non-receipt of one or two HRMs. KEY RESULTS:
      Approximately 21 % of MA enrollees received at least one HRM and 4.8 % received
      at least two. In fully adjusted models, females had a 10.6 (95 % CI: 10.0-11.2)
      higher percentage point rate of receipt than males, and residence in any of the
      Southern United States divisions was associated with a greater than 10 percentage
      point higher rate, as compared with the reference New England division. Higher
      rates were also observed among enrollees with low personal income (6.5 percentage
      points, 95 % CI: 5.5-7.5), relative to those without low income and those
      residing in areas in the lowest quintile of socioeconomic status (2.7 points, 95
      % CI: 1.9-3.4) relative to persons residing in the highest quintile. Enrollees >=
      85 years old, black enrollees, and other minority groups were less likely to
      receive these medications. Over 38 % of MA enrollees residing in the hospital
      referral region of Albany, Georgia received at least one HRM, a rate four times
      higher than the referral region with the lowest rate (Mason City, Iowa).
      CONCLUSIONS: Use of HRMs among MA enrollees varies widely by geographic region.
      Persons living in the Southern region of the U.S., whites, women, and persons of
      low personal income and socioeconomic status are more likely to receive HRMs.

PMID- 23129160
TI  - Physicians, social media, and conflict of interest.
AB  - Physicians and patients increasingly use social media technologies, such as
      Facebook, Twitter, and weblogs (blogs), both professionally and personally.
      Amidst recent reports of physician misbehavior online, as well as concerns about
      social media's potential negative effect on trust in the medical profession,
      several national-level physician organizations have created professional
      guidelines on social media use by physicians. Missing from these guidelines is
      adequate attention to conflict of interest. Some guidelines do not explicitly
      mention conflict of interest; others recommend only disclosure. Recommending
      disclosure fails to appreciate the unique features of social media that make
      adequate disclosure difficult to accomplish. Moreover, in emphasizing disclosure
      alone, current guidelines are inconsistent with medicine's general trend toward
      management or elimination, not just disclosure, of potential conflicts. Because
      social media sites typically rely on physicians' voluntary compliance with
      professional norms, physicians necessarily play a major role in shaping these
      norms' content and scope. To achieve the benefits of social media and ensure the
      veracity of social media content while preserving trust in the profession,
      physicians must reaffirm their commitment to disclose potential conflicts;
      advocate for better electronic disclosure mechanisms; and develop concrete
      management strategies-including, where necessary, the elimination of conflicts
      altogether.

PMID- 23129161
TI  - Utility of a brief screening tool to identify physicians in distress.
AB  - BACKGROUND: Despite a high prevalence of distress, few physicians seek help.
      Earlier identification of physicians in distress has been hampered by the lack of
      a brief screening instrument to assess the common forms of distress. OBJECTIVE:
      To evaluate the ability of the seven-item Physician Well-Being Index (PWBI) to i)
      stratify physician well-being in several important dimensions (mental quality of
      life [QOL], fatigue, suicidal ideation); and ii) identify physicians whose degree
      of distress may negatively impact their practice (career satisfaction, intent to
      leave current position, medical errors). DESIGN: Cross-sectional study.
      PARTICIPANTS: National sample of 6,994 U.S. physicians. MAIN MEASURES: PWBI,
      Mental QOL, fatigue, suicidal ideation, career satisfaction,and clinical practice
      measures. KEY RESULTS: Physicians with low mental QOL, high fatigue, or recent (<
      12 months) suicidal ideation were more likely to endorse each of the seven PWBI
      items and a greater number of total items (all P < 0 .001). Assuming a prevalence
      of 19 %, the PWBI could reduce the post-test probability of a physician having
      low mental QOL to < 1 % or raise it to > 75 %. The likelihood ratio for low
      mental QOL among physicians with PWBI scores >= 4 was 3.85 in comparison to 0.33
      for those with scores < 4. At a threshold score of >4, the PWBI's specificity for
      identifying physicians with low mental QOL, high fatigue, or recent suicidal
      ideation were 85.8 %. PWBI score also stratified physicians' career satisfaction,
      reported intent to leave current practice, and self-reported medical errors.
      CONCLUSIONS: The seven-item PWBI appears to be a useful screening index to
      identify physicians with distress in a variety of dimensions and whose degree of
      distress may negatively impact their practice.

PMID- 23129162
TI  - Variation in length of stay and outcomes among hospitalized patients attributable
      to hospitals and hospitalists.
AB  - BACKGROUND: There have been no prior population-based studies of variation in
      performance of hospitalists. OBJECTIVE: To measure the variation in performance
      of hospitalists. DESIGN: Retrospective research design of 100 % Texas Medicare
      data using multilevel, multivariable models. SUBJECTS: 131,710 hospitalized
      patients cared for by 1,099 hospitalists in 268 hospitals from 2006-2009. MAIN
      MEASURES: We calculated, for each hospitalist, adjusted for patient and disease
      factors (case mix), their patients' average length of stay, rate of discharge
      home or to skilled nursing facility (SNF) and rate of 30-day mortality,
      readmissions and emergency room (ER) visits. KEY RESULTS: In two-level models
      (admission and hospitalist), there was significant variation in average length of
      stay and discharge location among hospitalists, but very little variation in 30
      day mortality, readmission or emergency room visit rates. There was stability
      over time (2008-2009 vs. 2006-2007) in hospitalist performance. In three-level
      models including admissions, hospitalists and hospitals, the variation among
      hospitalists was substantially reduced. For example, hospitals, hospitalists and
      case mix contributed 1.02 %, 0.75 % and 42.15 % of the total variance in 30-day
      mortality rates, respectively. CONCLUSIONS: There is significant variation among
      hospitalists in length of stay and discharge destination of their patients, but
      much of the variation is attributable to the hospitals where they practice. The
      very low variation among hospitalists in 30-day readmission rates suggests that
      hospitalists are not important contributors to variations in those rates among
      hospitals.

PMID- 23129163
TI  - Supplementing cross-cover communication with the patient acuity rating.
AB  - BACKGROUND: Patient hand-offs at physician shift changes have limited ability to
      convey the primary team's longitudinal insight. The Patient Acuity Rating (PAR)
      is a previously validated, 7-point scale that quantifies physician judgment of
      patient stability, where a higher score indicates a greater risk of clinical
      deterioration. Its impact on cross-covering physician understanding of patients
      is not known. OBJECTIVE: To determine PAR contribution to sign-outs. DESIGN:
      Cross-sectional survey. SUBJECTS: Intern physicians at a university teaching
      hospital. INTERVENTIONS: Subjects were surveyed using randomly chosen, de
      identified patient sign-outs, previously assigned PAR scores by their primary
      teams. For each sign-out, subjects assigned a PAR score, then responded to
      hypothetical cross-cover scenarios before and after being informed of the primary
      team's PAR. MAIN MEASURE: Changes in intern assessment of the scenario before and
      after being informed of the primary team's PAR were measured. In addition,
      responses between novice and experienced interns were compared. KEY RESULTS:
      Between May and July 2008, 23 of 39 (59 %) experienced interns and 25 of 42 (60
      %) novice interns responded to 480 patient scenarios from ten distinct sign-outs.
      The mean PAR score assigned by subjects was 4.2 +/- 1.6 vs. 3.8 +/- 1.8 by the
      primary teams (p < 0.001). After viewing the primary team's PAR score, interns
      changed their level of concern in 47.9 % of cases, their assessment of the
      importance of immediate bedside evaluation in 48.7 % of cases, and confidence in
      their assessment in 43.2 % of cases. For all three assessments, novice interns
      changed their responses more frequently than experienced interns (p = 0.03,
      0.009, and <0.001, respectively). Overall interns reported the PAR score to be
      theoretically helpful in 70.8 % of the cases, but this was more pronounced in
      novice interns (81.2 % vs 59.6 %, p < 0.001). CONCLUSIONS: The PAR adds valuable
      information to sign-outs that could impact cross-cover decision-making and
      potentially benefit patients. However, correct training in its use may be
      required to avoid unintended consequences.

PMID- 23129165
TI  - Out-of-pocket medical spending and Charon's obol.

PMID- 23129164
TI  - The art of bedside rounds: a multi-center qualitative study of strategies used by
      experienced bedside teachers.
AB  - BACKGROUND: Medical educators believe bedside rounds are effective for the
      delivery of patient-centered care, and are necessary in helping trainees acquire
      competence in clinical care. Although recommendations for bedside rounds have
      been reported, a recent, systematic assessment of strategies used by current-day
      bedside teachers was needed to advance knowledge of this teaching method.
      OBJECTIVE: To identify and understand bedside teachers' 1) preparatory steps, 2)
      patient selection, and 3) role allocation during the process of bedside rounds.
      DESIGN: A qualitative inductive thematic analysis using transcripts from audio
      recorded, semi-structured telephone interviews. PARTICIPANTS: Internal medicine
      physicians (n = 34) who perform bedside rounds from ten academic US institutions
      (2010-2011). APPROACH: A purposive sampling strategy was utilized to identify
      physicians who were active inpatient attending physicians and met specific
      inclusion criteria for "bedside rounds." A total of 34 interviews were completed,
      and each was recorded and transcribed verbatim. A thematic analysis extracted key
      themes pertaining to the three objectives. KEY RESULTS: Most respondents (51 %)
      were associate or full professors, with an average of 14 years of academic
      experience. Attending physicians prepared using trainee-specific, patient
      specific and disease-specific information, while also mentally preparing for
      bedside rounds. They sought trainee buy-in and learning objectives, reviewed
      expectations and methods to ensure patient comfort, and provided early guidance
      with bedside encounters. Patients were selected if they required immediate care,
      were new to the service, or had a high educational value, while patients were
      deferred if unavailable, unwilling, or unable to communicate. The team members'
      roles during bedside rounds varied, with trainees being given graduated autonomy
      with increased experience. CONCLUSIONS: Bedside teachers' methods for
      preparation, patient selection, and role allocation during bedside rounds enhance
      trainees' education within the workplace. Strategies used by experienced bedside
      teachers can be used for faculty development efforts aimed at promoting this
      activity.

PMID- 23129166
TI  - Reproductive and hormonal factors and the risk of lung cancer: the EAGLE study.
AB  - Evidence about the role for reproductive and hormonal factors in the etiology of
      lung cancer in women is conflicting. To clarify this question, we examined 407
      female cases and 499 female controls from the Environment And Genetics in Lung
      cancer Etiology population-based case-control study. Subjects were interviewed in
      person using a computer-assisted personal interview to assess demographics,
      education, smoking history, medical history, occupational history, reproductive
      and hormonal factors. Associations of interest were investigated using logistic
      regression models, adjusted for catchment area and age (matching variables),
      cigarette smoking (status, pack-years and time since quitting). Additional
      confounding variables were investigated but did not substantially affect the
      results. We observed a reduced risk of lung cancer among women with later age at
      first live birth [>=31 years: odds ratio (OR) = 0.57, 95% confidence interval
      (CI) = 0.31-1.06, p-trend = 0.05], later age at menopause (>=51 years: OR = 0.49,
      95%CI = 0.31-0.79, p-trend = 0.003) and longer reproductive periods (>=41 years:
      OR = 0.44, 95%CI = 0.25-0.79, p-trend = 0.01). A reduced risk was also observed
      for hormone replacement therapy (OR = 0.63, 95%CI = 0.42-0.95, p = 0.03) and oral
      contraceptive use (OR = 0.67, 95%CI = 0.45-1.00, p = 0.05) but no trend with
      duration of use was detected. Menopausal status (both natural and induced) was
      associated with an augmented risk. No additional associations were identified for
      other reproductive variables. This study suggests that women who continue to
      produce estrogens have a lower lung cancer risk. Large studies with great number
      of never smoking women, biomarkers of estrogen and molecular classification of
      lung cancer are needed for a more comprehensive view of the association between
      reproductive factors and lung cancer risk.

PMID- 23129167
TI  - Fluorescence of a histidine-modified enhanced green fluorescent protein (EGFP)
      effectively quenched by copper(II) ions.
AB  - Two histidines were introduced by site-directed mutagenesis into the structure of
      Enhanced Green Fluorescent Protein, replacing the serine at position 202 and the
      glutamine at position 204 for increasing the sensitivity of the protein towards
      different metal ions by creating possible metal binding sites near the
      chromophore group. There is no appreciable difference between the absorbance and
      fluorescence spectra of the two proteins (wild type and the double-histidine
      mutant) indicating that the mutation does not change the environment of the
      fluorophore. Fluorescence quenching was measured at different pH (6.5-8) and
      temperatures (20-45  degrees C) varying the concentration of metal ions. Under
      optimal conditions (pH = 7.5, 20  degrees C) the mutant's Kd is 16 nM, it binds
      copper more than 200fold stronger than the wild type EGFP.

PMID- 23129168
TI  - Pleomorphic spindle cell sarcoma (PSCS) formerly known as malignant fibrous
      histiocytoma (MFH): a complex malignant soft-tissue tumor.
AB  - A presentation defining the nature, characteristics, causation, treatment and
      outcome of patients with lesions formerly known as malignant fibrous histiocytoma
      and now as pleomorphic spindle cell sarcoma is clearly a very difficult subject.
      Many authors do not believe that the tumor exists and instead describe them as
      forms of fibrosarcomas, fibromyxoid lesions, dedifferentiated chondrosarcomas or
      even leiomyosarcomas. The reasons for this confusion are presumably related to
      the fact that the malignant pleomorphic spindle cell sarcoma does not seem to be
      a distinct type of lesion with specific histologic and genetic characteristics.
      Instead, the tumor has at least four separate histologic variations and no
      specific gene signature and in fact does not seem to be either familial or ethnic
      in presentation. In view of the fact that the tumor was traditionally the most
      frequently encountered malignant soft-tissue neoplasm, the world of orthopedic
      oncology is clearly distressed by the problems that these patients have and is
      joined by the radiation oncologists and chemotherapists in seeking new solutions.

PMID- 23129169
TI  - New curable propylene copolymers containing tert-butoxysilane side groups.
AB  - In this work, new, crosslinkable copolymers from propylene and di-tert
      butoxy(methyl)(oct-7-enyl)silane are presented. The silane-functionalized monomer
      is obtained by hydrosilylation of 1,7-octadiene with dichloromethylsilane,
      followed by the substitution of the chloro atoms by tert-butoxy groups.
      Homopolymerization and copolymerization with propylene are performed using rac
      [ethylenebis(indenyl)]zirconium dichloride. The tert-butoxysilane groups are
      easily cleaved by acid-catalyzed processes. The resulting copolymer can be
      completely crosslinked via the tert-butoxysilane functionality to obtain
      insoluble polymeric material and the gel content of the polymers with different
      silane content is determined. This method allows control of the copolymer
      composition and thus of the subsequent extent of crosslinking.

PMID- 23129170
TI  - Synthesis and fluorescence study of a quaternized copolymer containing pyrene for
      DNA-hybridization detection.
AB  - Built-in detector: A quaternized copolymer containing pyrene is described, which
      can bind to single-stranded DNA by electrostatic interactions to form a novel
      complex probe for the detection of DNA hybridization through strengthened
      fluorescence quenching through its intercalation into double-stranded DNA (see
      figure).

PMID- 23129171
TI  - The association between socioeconomic status and survival among children with
      Hodgkin and non-Hodgkin lymphomas in a universal health care system.
AB  - BACKGROUND: The association between socioeconomic status (SES) and cancer
      survival has been studied extensively in adults. However, little is known about
      this relationship in the pediatric population, specifically in jurisdictions with
      universal health care insurance programs. Our aim was to determine whether lower
      SES is associated with poorer survival in pediatric Hodgkin (HL) and non-Hodgkin
      lymphoma (NHL) patients in Ontario. PROCEDURE: All incident cases of HL and NHL
      in children between 0 and 14 years old diagnosed in Ontario between January 1st,
      1985 and December 31st, 2006 were identified through the Pediatric Oncology Group
      of Ontario Networked Information System. Neighborhood income quintile and
      material deprivation quintile at diagnosis were used as proxies for SES. Cox
      proportional hazards regressions were used to assess the association between SES
      and the risk of event-free or overall survival. RESULTS: A total of 692 patients
      were included in the analysis: 302 HL and 390 NHL. SES was not associated with
      survival (overall or event-free) among HL and NHL patients (P > 0.05 for all four
      comparisons, i.e., HL/NHL, EFS/OS) after adjustment for age, sex, period of
      diagnosis, and disease stage. There were no differences in the distribution of
      disease stage across SES strata at the time of diagnosis. Similarly, the
      distribution of deaths among long-term survivors (survived >=5 years from
      diagnosis) did not differ across SES strata (P > 0.05). CONCLUSIONS: SES was not
      associated with risk of death among pediatric HL and NHL patients in Ontario.
      This was consistent through the cancer trajectory, including diagnosis,
      treatment, and survivorship.

PMID- 23129172
TI  - Detection of disseminated tumor cells in the bone marrow of breast cancer
      patients using multiplex gene expression measurements identifies new therapeutic
      targets in patients at high risk for the development of metastatic disease.
AB  - Disseminated tumor cells (DTCs) detected in the bone marrow (BM) of breast cancer
      patients identify women at high risk of recurrence. DTCs are traditionally
      detected by immunocytochemical staining for cytokeratins or single gene
      expression measurements, which limit both specificity and sensitivity. We
      evaluated the Nanostring nCounterTM platform for multi-marker, gene expression
      based detection and classification of DTCs in the BM of breast cancer patients.
      Candidate genes exhibiting tumor cell-specific expression were identified from
      microarray datasets and validated by qRT-PCR analysis in non-malignant human BM
      and identical samples spiked with predefined numbers of molecularly diverse
      breast tumor cell lines. Thirty-eight validated transcripts were designed for the
      nCounterTM platform and a subset of these transcripts was technically validated
      against qRT-PCR measurements using identical spiked BM controls. Bilateral iliac
      crest BM aspirates were collected and analyzed from twenty breast cancer
      patients, prior to neoadjuvant therapy, using the full 38-gene nCounterTM code
      set. Tumor cell-specific gene expression by nCounterTM was detected with a
      sensitivity of one cancer cell per 1 * 10(6) nucleated BM cells after
      optimization. Measurements were quantitative, log linear over a 20-fold range,
      and correlated with qRT-PCR measurements. Using the nCounterTM 38-gene panel, 6
      of 8 patients (75 %) who developed metastatic disease had detectable expression
      of at least one transcript. Notably, three of these patients had detectable
      expression of ERBB2 in their BM, despite the fact that their corresponding
      primary tumors were HER2/ERBB2 negative and therefore did not receive trastuzumab
      therapy. Four of these patients also expressed the PTCH1 receptor, a newly
      recognized therapeutic target based on hedgehog signaling pathway inhibition. The
      presumptive detection and classification of DTCs in the BM of breast cancer
      patients, based on sensitive and quantitative multi-marker detection of gene
      expression using the nCounterTM platform, provide an opportunity to both predict
      early distant recurrence and, more importantly, identify opportunities for
      preventing the spread of disease based on the expression of unique,
      therapeutically actionable gene targets. This study demonstrates the application
      of a new technology for multiplexed gene expression-based detection of DTCs in
      the BM of breast cancer patients and identifies at least two therapeutically
      targetable genes that are frequently expressed in the BM of patients who develop
      metastatic disease.

PMID- 23129173
TI  - Plasma estrone sulfate concentrations and genetic variation at the CYP19A1 locus
      in postmenopausal women with early breast cancer treated with letrozole.
AB  - Estrogen synthesis suppression induced by aromatase inhibitors in breast cancer
      (BC) patients may be affected by single nucleotide polymorphisms (SNPs) of the
      gene encoding aromatase enzyme, CYP19A1. We assessed the association between
      plasma estrone sulfate (ES), letrozole treatment, and four SNPs of CYP19A1 gene
      (rs10046 C>T, rs4646 G>T, rs749292 C>T, rs727479 T>G) which seem to be related to
      circulating estrogen levels. Patients were enrolled into a prospective, Italian
      multi-center clinical trial (Gruppo Italiano Mammella, GIM-5) testing the
      association of CYP19A1 SNPs with the efficacy of letrozole adjuvant therapy, in
      postmenopausal early BC patients. SNPs were identified from peripheral blood cell
      DNA. Plasma ES concentrations were evaluated by Radio Immuno Assay. Blood samples
      were obtained immediately before letrozole therapy (N = 204), at 6-weeks (N =
      178), 6 (N = 152) and 12-months (N = 136) during treatment. Medians (IQR) of ES
      were 160 pg/mL (85-274) at baseline, 35 pg/mL (12-64) at 6-weeks, 29 pg/mL (17
      48) at 6 months and 25 pg/mL (8-46) after 12 months treatment. No statistically
      significant association was evident between polymorphisms and ES circulating
      levels during letrozole therapy. Letrozole suppression of the aromatase enzyme
      function is not affected by polymorphisms of CYP19A1 gene in postmenopausal BC
      patients.

PMID- 23129174
TI  - Patients' willingness to participate in a breast cancer biobank at screening
      mammogram.
AB  - To characterize patients' willingness to donate a biospecimen for future research
      as part of a breast cancer-related biobank involving a general screening
      population. We performed a prospective cross-sectional study of 4,217 women aged
      21-89 years presenting to our facilities for screening mammogram between December
      2010 and October 2011. This HIPAA-compliant study was approved by our
      institutional review board. We collected data on patients' interest in and actual
      donation of a biospecimen, motivators and barriers to donating, demographic
      information, and personal breast cancer risk factors. A multivariate logistic
      regression analysis was performed to identify patient-level characteristics
      associated with an increased likelihood to donate. Mean patient age was 57.8
      years (SD 11.1 years). While 66.0 % (2,785/4,217) of patients were willing to
      donate blood or saliva during their visit, only 56.4 % (2,378/4,217) actually
      donated. Women with a college education (OR = 1.27, p = 0.003), older age (OR =
      1.02, p < 0.001), previous breast biopsy (OR = 1.23, p = 0.012), family history
      of breast cancer (OR = 1.23, p = 0.004), or a comorbidity (OR = 1.22, p = 0.014)
      were more likely to donate. Asian-American women were significantly less likely
      to donate (OR = 0.74, p = 0.005). The major reason for donating was to help all
      future patients (42.3 %) and the major reason for declining donation was privacy
      concerns (22.3 %). A large proportion of women participating in a breast cancer
      screening registry are willing to donate blood or saliva to a biobank. Among
      minority participants, Asian-American women are less likely to donate and further
      qualitative research is required to identify novel active recruitment strategies
      to insure their involvement.

PMID- 23129175
TI  - Morbidity following thyroid surgery: does surgeon volume matter?
AB  - PURPOSE: The aim of our study was to analyze the relationship between surgeon
      volume and morbidity in patients operated on by surgeons with endocrine
      specialization (EndS group) and those operated on by general surgeons (GenS
      group) in a single tertiary institution. METHODS: We present the results of a
      prospective cohort study of all patients undergoing thyroid surgery in our
      institution between January 2008 and January 2010, all of whom attended for
      follow-up for at least 12 months. We assessed pre- and postoperative recurrent
      laryngeal nerve (RLN) function by laryngoscopy. We monitored serum calcium
      concentrations in all patients until these values were normal without vitamin D
      and oral calcium supplementation. RESULTS: We studied 225 patients: 30 in the
      GenS group (six surgeons performing <5 procedures per surgeon per year) and 195
      in the EndS group (two surgeons performing >40 procedures per surgeon per year).
      The total number of exposed RLN was 46 and 325, respectively. The incidence of
      RLN palsy persisting beyond 12 months was higher in the GenS group (2/46 vs.
      1/325 exposed RLNs, p = 0.04). The incidence of hypocalcaemia persisting beyond
      12 months (bilateral procedures) was also higher in the GenS group (3/16 vs.
      3/130 patients, p = 0.028). CONCLUSIONS: Morbidity in terms of permanent RLN
      palsy and hypocalcaemia was less frequent among patients operated on by endocrine
      dedicated surgeons. Differences in surgical volume and specialized training in
      neck endocrine surgery may explain these variations in morbidity.

PMID- 23129176
TI  - Notch pathway is involved in high glucose-induced apoptosis in podocytes via Bcl
      2 and p53 pathways.
AB  - Recent studies have shown that Notch pathway plays a key role in the pathogenesis
      of diabetic nephropathy (DN), however, the exact mechanisms remain elusive. Here
      we demonstrated that high glucose (HG) upregulated Notch pathway in podocytes
      accompanied with the alteration of Bcl-2 and p53 pathways, subsequently leading
      to podocytes apoptosis. Inhibition of Notch pathway by chemical inhibitor or
      specific short hairpin RNA (shRNA) vector in podocytes prevented Bcl-2- and p53
      dependent cell apoptosis. These findings suggest that Notch pathway mediates HG
      induced podocytes apoptosis via Bcl-2 and p53 pathways.

PMID- 23129177
TI  - Transforming growth factor-beta 1 enhances the invasiveness of breast cancer
      cells by inducing a Smad2-dependent epithelial-to-mesenchymal transition.
AB  - Metastasis is unequivocally the most lethal aspect of breast cancer and the most
      prominent feature associated with disease recurrence, the molecular mechanisms
      whereby epithelial-to-mesenchymal transition (EMT) mediates the initiation and
      resolution of breast cancer metastasis remains poorly understood. Transforming
      growth factor-beta1 (TGF-beta1) is a multifunctional cytokine that is intimately
      involved in regulating numerous physiological processes, including cellular
      differentiation, homeostasis and EMT. Recent findings have implicated high levels
      of TGF-beta1 were associated with poor outcome, whereas inhibition of TGF-beta
      signaling reduces metastasis in breast cancer, suggesting that the chemo
      therapeutic targeting of TGF-beta1 or TGF-beta signaling may offer new inroads in
      ameliorating metastatic disease in breast cancer patients. In this study, we
      showed immunohistochemical evidence for EMT, which is associated with TGF-beta1
      expression, at the invasion front of breast cancer in vivo. The data also
      indicated that human breast cancer cell lines, MCF-7 and MDA-MB-435S, of
      epithelial cell characteristics were induced to undergo EMT by TGF-beta1 and
      dependent on the Smad2 signaling pathway. Following TGF-beta1 treatment, cells
      showed dramatic morphological changes assessed by phase contrast microscopy,
      accompanied by decreased epithelial marker and increased mesenchymal markers.
      Importantly, cell invasion was also enhanced in the EMT process, while knockdown
      of the Smad2 gene by silencing siRNA partially inhibited these effects in MDA
      MB435S (P<0.05). These data suggested that EMT of breast cancer induced by TGF
      beta1 is dependent on Smad2 signaling and promotes breast cancer cell metastasis.

PMID- 23129178
TI  - A multifunctional porous organic Schottky barrier diode.
AB  - Mesoporous materials: A multifunctional porous organic material (ANPPIT; see
      picture) has been synthesized and characterized. Multifunctionality of the
      compound has been determined from nitrogen adsorption, guest-dependent
      luminescence, and electrical conductivity measurements.

PMID- 23129179
TI  - Evidence for primary laryngeal inhalant allergy: a randomized, double-blinded
      crossover study.
AB  - BACKGROUND: Despite anecdotal reports, no controlled studies to date link
      allergen exposure with a change in vocal function or dysphonia. The aim of this
      study was to determine whether allergen exposure in susceptible individuals
      impairs vocal function. METHODS: The study was a prospective, double-blind,
      placebo-controlled study in which subjects serve as their own controls. The
      participants were 5 inhalant allergic adults with suspected dysphonia from
      allergies, without evidence of reactive lower airways based on methacholine
      challenge. All subjects were exposed to 2 experimental conditions in which they
      were challenged with (1) orally inhaled diluent placebo on 1 day, and (2) orally
      inhaled allergen on another day. Conditions were randomly ordered across subjects
      and separated by at least 48 hours. Phonatory threshold pressure (PTP) at the
      80th percentile pitch was measured prior to diluent and allergen challenge, and
      15 and 60 minutes postchallenge to assess potential change in vocal function
      after challenge testing. RESULTS: A repeated measures ANOVA revealed a
      significant main effect for treatment (allergen vs placebo, p = 0.013) with
      greater PTP required post-allergen challenge compared to placebo and an effect
      size of 0.821. CONCLUSION: A primary causal relationship between allergen
      exposure and impaired vocal function, as assessed by PTP, was observed in adults
      with documented allergy independent of asthma or nasal exposure. The current
      design establishes a safe model for laryngeal inhalant allergen challenge.

PMID- 23129181
TI  - Site-saturation engineering of lysine 47 in cyclodextrin glycosyltransferase from
      Paenibacillus macerans to enhance substrate specificity towards maltodextrin for
      enzymatic synthesis of 2-O-D-glucopyranosyl-L-ascorbic acid (AA-2G).
AB  - In this work, the site-saturation engineering of lysine 47 in cyclodextrin
      glycosyltransferase (CGTase) from Paenibacillus macerans was conducted to improve
      the specificity of CGTase towards maltodextrin, which can be used as a cheap and
      easily soluble glycosyl donor for the enzymatic synthesis of 2-O-D-glucopyranosyl
      L-ascorbic acid (AA-2G) by CGTase. When using maltodextrin as glycosyl donor,
      four mutants K47F (lysine-> phenylalanine), K47L (lysine-> leucine), K47V (lysine
      > valine) and K47W (lysine-> tryptophan) showed higher AA-2G yield as compared
      with that produced by the wild-type CGTase. The transformation conditions
      (temperature, pH and the mass ratio of L-ascorbic acid to maltodextrin) were
      optimized and the highest titer of AA-2G produced by the mutant K47L could reach
      1.97 g/l, which was 64.2% higher than that (1.20 g/l) produced by the wild-type
      CGTase. The reaction kinetics analysis confirmed the enhanced maltodextrin
      specificity, and it was also found that compared with the wild-type CGTase, the
      four mutants had relatively lower cyclization activities and higher
      disproportionation activities, which was favorable for AA-2G synthesis. The
      mechanism responsible for the enhanced substrate specificity was further explored
      by structure modeling and it was indicated that the enhancement of maltodextrin
      specificity may be due to the short residue chain and the removal of hydrogen
      bonding interactions between the side chain of residue 47 and the sugar at -3
      subsite. Here the obtained mutant CGTases, especially the K47L, has a great
      potential in the production of AA-2G with maltodextrin as a cheap and easily
      soluble substrate.

PMID- 23129180
TI  - Eldecalcitol reduces the risk of severe vertebral fractures and improves the
      health-related quality of life in patients with osteoporosis.
AB  - Eldecalcitol reduces the risk of vertebral fractures in comparison to
      alfacalcidol in osteoporotic patients under vitamin D repletion. The aim of this
      study was to evaluate the effects of eldecalcitol on the spinal location of
      incident vertebral fractures, the severity of the fractures, and the changes in
      health-related quality of life (HRQOL) compared with those of alfacalcidol. The
      post hoc analysis has been performed on the data from the three-year, double
      blind, randomized, head-to-head clinical trial of eldecalcitol versus
      alfacalcidol conducted in Japan. A total of 1054 patients were enrolled and
      randomized to take 0.75 MUg eldecalcitol or 1.0 MUg alfacalcidol daily for 3
      years. The incidence of vertebral fractures was re-evaluated based on the
      location on the spine (upper T4-T10; lower T11-L4). The severity of vertebral
      fractures was determined by the semi-quantitative method, and the change in HRQOL
      was analyzed by using the Medical Outcomes Study Short Form 36-item
      questionnaire. The incidence of vertebral fracture at the lower spine was less in
      the eldecalcitol group than in the alfacalcidol group (p = 0.029). The incidence
      of severe vertebral fracture (Grade 3) was 3.8 % in the eldecalcitol group and
      6.7 % in the alfacalcidol group, demonstrated a significant difference between
      the 2 groups (p = 0.036). Both eldecalcitol and alfacalcidol improved HRQOL in
      osteoporotic patients. Although no significant differences in each HRQOL scores
      were observed between eldecalcitol and alfacalcidol during the observational
      period, overall improvement from baseline of HRQOL scores were clearly observed
      in the eldecalcitol group. In conclusion, the incidences of lower spinal
      vertebral fractures and severe vertebral fractures were reduced further by
      eldecalcitol compared to alfacalcidol in the 3-year clinical trial. Daily
      treatment with eldecalcitol is effective in improving HRQOL, possibly owing to
      the reduced risk of lower spinal vertebral fractures and/or severe vertebral
      fractures.

PMID- 23129182
TI  - Fermentation of quinoa and wheat slurries by Lactobacillus plantarum CRL 778:
      proteolytic activity.
AB  - Quinoa fermentation by lactic acid bacteria (LAB) is an interesting alternative
      to produce new bakery products with high nutritional value; furthermore, they are
      suitable for celiac patients because this pseudo-cereal contains no gluten.
      Growth and lactic acid production during slurry fermentations by Lactobacillus
      plantarum CRL 778 were greater in quinoa (9.8 log cfu/mL, 23.1 g/L) than in wheat
      (8.9 log cfu/mL, 13.9 g/L). Lactic fermentation indirectly stimulated flour
      protein hydrolysis by endogenous proteases of both slurries. However, quinoa
      protein hydrolysis was faster, reaching 40-100% at 8 h of incubation, while wheat
      protein hydrolysis was only 0-20%. In addition, higher amounts of peptides (24)
      and free amino acids (5 g/L) were determined in quinoa compared to wheat.
      Consequently, greater concentrations (approx. 2.6-fold) of the antifungal
      compounds (phenyllactic and hydroxyphenyllactic acids) were synthesized from Phe
      and Tyr in quinoa by L. plantarum CRL 778, an antifungal strain. These promising
      results suggest that this LAB strain could be used in the formulation of quinoa
      sourdough to obtain baked goods with improved nutritional quality and shelf life,
      suitable for celiac patients.

PMID- 23129183
TI  - A mechanism for NaCl inhibition of Reactive Blue 19 decolorization and ABTS
      oxidation by laccase.
AB  - Laccases produced by white rot fungi have been extensively evaluated for their
      potential to decolorize textile wastewaters which contain salts like sodium
      chloride and sodium sulfate. The effect of sodium chloride and sodium sulfate on
      Trametes versicolor laccase during the decolorization of an anthraquinone dye
      (Reactive Blue 19) and the oxidation of 2,2'-azino-bis(3-ethylbenzothiazoline-6
      sulfonic acid) (ABTS) were evaluated by steady-state kinetic analysis. The
      results showed that, while sodium sulfate did not affect laccase activity, sodium
      chloride inhibited both ABTS oxidation and dye decolorization. However, the type
      of inhibition was substrate-dependent: it was hyperbolic, noncompetitive with
      ABTS and parabolic, noncompetitive with Reactive Blue 19. Furthermore, the
      results suggested that two chlorides may bind to laccase in the presence of the
      dye unlike recent inhibition models which suggest that there is only one
      inhibition site. This investigation is the first to provide evidence for and to
      propose a two-site model of laccase inhibition, providing new insight into NaCl
      inhibition of laccase. The proposed model is also useful to predict
      decolorization rates in the presence of sodium chloride and to determine
      operating conditions that will minimize inhibition. 

PMID- 23129184
TI  - Assessment of Schwanniomyces occidentalis as a host for protein production using
      the wide-range Xplor2 expression platform.
AB  - The wide-range transformation/expression platform, Xplor2, was employed for the
      assessment of Schwanniomyces occidentalis as a potential producer of the
      recombinant proteins human IFNalpha2a (IFNalpha2a) and S. occidentalis
      fructofuranosidase (SFfase), and its efficiency was compared to that of Arxula
      adeninivorans. ADE2 and URA3 genes from both yeast species were isolated,
      characterized and used as selection markers in combination with the IFNalpha2a
      and SFfase expression modules, which used the strong constitutive A.
      adeninivorans-derived TEF1 promoter. Yeast rDNA integrative expression cassettes
      and yeast integrative expression cassettes equipped with a selection marker and
      expression modules were transformed into auxotrophic S. occidentalis and A.
      adeninivorans strains and a quantitative comparison of the expression efficiency
      was made. Whilst IFNalpha2a was mainly accumulated extracellularly (>95 %) in A.
      adeninivorans, extracellular SFfase (>90 %) was detected in both yeast species.
      The DNA composition of the selection marker modules and expression modules,
      especially their open reading frame codon usage, affects auxotrophy recovery as
      well as protein expression. Auxotrophy recovery was only achieved with selection
      marker modules of the homologous gene donor yeast. The concentration of
      recombinant IFNalpha2a was fivefold higher in A. adeninivorans (1 mg L(-1)),
      whereas S. occidentalis accumulated 1.5- to 2-fold more SFfase (0.5 Units ml(
      1)). These results demonstrate the extension of the use of the wide-range
      expression platform Xplor2 to another yeast species of biotechnological interest.

PMID- 23129185
TI  - Cross-talk of alpha tocopherol-associated protein and JNK controls the oxidative
      stress-induced apoptosis in prostate cancer cells.
AB  - Excess intracellular reactive oxygen species (ROS) beyond a threshold can induce
      apoptosis in cancer cells. However, the signal pathways that can augment the
      proapoptotic function of ROS remain largely unknown. We previously identified a
      tumor suppressor, alpha-tocopherol-associated protein (TAP), yet little is known
      regarding the role of TAP in the apoptotic signaling in prostate cancer.
      Interestingly, we recently found that exposure of prostate cancer cells to
      hydrogen peroxide (H(2)O(2) ) resulted in induced apoptosis as well as increased
      expression of TAP. Small interfering RNA (siRNA) mediated silencing of endogenous
      TAP expression conferred effective protection from H(2)O(2) -induced apoptosis.
      Further mechanistic study showed exposure of prostate cancer cells to H(2)O(2)
      resulted in increased phosphorylation of both JNK and c-Jun, and TAP siRNA
      effectively decreased H(2)O(2) -induced JNK and c-Jun phosphorylation.
      Immunoprecipitation experiments revealed that JNK physically associates with TAP.
      Furthermore, signaling downstream of JNK to the AP-1 complex and BH-3-only
      subfamily were found to be regulated on changing the TAP expression status. TAP
      could also promote the oxidative stress-induced apoptosis effect of docetaxel. In
      the mice xenograft model, H(2)O(2) treatment induced TAP expression, JNK
      phosphorylation and apoptosis of prostate cancer. Recombinant adeno-associated
      virus 2 (rAAV2)-TAP injection significantly sensitizes this H(2)O(2) proapoptotic
      effect. Together, we have identified a novel functional mechanism that the cross
      talk of TAP-JNK is involved in oxidative stress-induced apoptosis in prostate
      cancer cells. Disrupting the redox balance of cancer cells by this signaling may
      enable therapeutic selectivity and provide benefit to overcome the drug
      resistance of prostate cancer.

PMID- 23129187
TI  - Low-dose 3D (82)Rb PET.

PMID- 23129186
TI  - Comparison of different focusing fiber tips for improved oral diode laser
      surgery.
AB  - BACKGROUND AND OBJECTIVES: State of the art for use of the fiber guided diode
      laser in dental therapy is the application of bare fibers. A novel concept with
      delivery fiber and exchangeable fiber tips enables the use of tips with special
      and optimized geometries for various applications. The aim of this study is the
      comparison of different focusing fiber tips for enhanced cutting efficacy in oral
      surgery. MATERIAL AND METHODS: For this purpose various designs of tip geometry
      were investigated and optimized by ray tracing simulations. Two applicators, one
      with a sphere, and another one with a taper, were realized and tested on porcine
      gingiva (diode laser, 940 nm, 5 W/cw; 7 W/modulated). The cutting depth and
      quality were determined by light microscope. Histological sections of the cuts
      were prepared by a cryo-microtome and microscopically analyzed to determine the
      cut depths and thermal damage zones. RESULTS: The simulations show that, using a
      sphere as fiber tip, an intensity increase of up to a factor of 16.2 in air, and
      13.2 in water compared to a bare 200 um fiber can be achieved. Although offering
      high focusing factor in water, the cutting quality of the sphere was rather poor.
      This is probably caused by a derogation of the focusing quality due to
      contamination during cutting and light scattering. Much better results were
      achieved with conically shaped fiber tips. Compared to bare fibers they exhibit
      improved handling properties with no hooking, more regular and deeper cuts (5
      W/cw: 2,393 +/- 468 um, compared to the cleaved bare fiber 5 W/cw: 711 +/- 268
      um). The thermal damage zones of the cuts are comparable for the various tips and
      fibers. CONCLUSIONS: In conclusion the results of our study show that cutting
      quality and efficiency of diode laser on soft tissue can be significantly
      improved using conically shaped fiber tips.

PMID- 23129188
TI  - Importance of physician-patient communication in cardiovascular care.

PMID- 23129191
TI  - Reciprocating motion of a self-propelled object on a molecular layer.
AB  - The mode change of a simple autonomous motor depending on the nature of a
      monolayer on water is investigated. A camphor disk is floated on a molecular
      layer of N-stearoyl-p-nitroaniline (C(18)ANA), which gives a surface-pressure
      (pi)-area per molecule (A) isotherm with a local maximum and a local minimum. The
      nature of the camphor motion changes depending on A, and in particular,
      reciprocating motion is observed at a lower A while cutting out its own
      trajectory of motion. The characteristic motion of a camphor disk depending on A
      is discussed in relation to the pi-A isotherm of C(18)ANA and the influence of
      the molecular interaction between molecules on the driving force of motion.

PMID- 23129190
TI  - Brief communication: the Granada osteological collection of identified infants
      and young children.
AB  - The objective of this study is to present the characteristics of a collection of
      identified infants and young children housed in the Laboratory of Anthropology of
      the University of Granada, Spain. The sample, which is still being enlarged, is
      currently composed of 230 complete skeletons aged from 5 months of gestation to 8
      years, with a majority below 1 year. It mainly dates from the mid-20th century.
      The state of preservation is very good, and antemortem information is available
      from burial and death certificates, among other documents. Our sample makes an
      important contribution to the relatively few collections available in the world
      for investigating the osteological development of the skeletons of infants and
      young children from a physical anthropological perspective.

PMID- 23129192
TI  - Apicomplexa primers amplify Proteromonas (Stramenopiles, Slopalinida,
      Proteromonadidae) in tissue and blood samples from lizards.
AB  - Microscopy has traditionally been the most common method in parasitological
      studies, but in recent years molecular screening has become increasingly frequent
      to detect protozoan parasites in a wide range of vertebrate hosts and vectors.
      During routine molecular screening of apicomplexan parasites in reptiles using
      the 18S rRNA gene, we have amplified and sequenced Proteromonas parasites from
      three lizard hosts (less than 1% prevalence). We conducted phylogenetic analysis
      to confirm the taxonomic position and infer their relationships with other
      stramenopiles. Although our phylogeny is limited due to scarcity of molecular
      data on these protists, our results confirm they are closely related to
      Proteromonas lacertae. Our findings show that unexpected parasites can be
      amplified from host samples (blood and tissue) using general procedures to detect
      hemoparasites, and stress that positive PCR amplifications alone should not be
      considered as definitive proof of infection by particular parasites. Further
      validation by sequence confirmation and thorough phylogenetic assessment will not
      only avoid false positives and biased prevalence estimates but also provide
      valuable information on the biodiversity and phylogenetic relationships of other
      parasitic organisms. More generally, our results illustrate the perils of general
      diagnosis protocols in parasitological studies and the need of cross-validation
      procedures.

PMID- 23129193
TI  - Molecular characterization and phylogenetic relationships among microsporidian
      isolates infecting silkworm, Bombyx mori using small subunit rRNA (SSU-rRNA) gene
      sequence analysis.
AB  - The life cycle, spore morphology, pathogenicity, tissue specificity, mode of
      transmission and small subunit rRNA (SSU-rRNA) gene sequence analysis of the five
      new microsporidian isolates viz., NIWB-11bp, NIWB-12n, NIWB-13md, NIWB-14b and
      NIWB-15mb identified from the silkworm, Bombyx mori have been studied along with
      type species, NIK-1s_mys. The life cycle of the microsporidians identified
      exhibited the sequential developmental cycles that are similar to the general
      developmental cycle of the genus, Nosema. The spores showed considerable
      variations in their shape, length and width. The pathogenicity observed was dose
      dependent and differed from each of the microsporidian isolates; the NIWB-15mb
      was found to be more virulent than other isolates. All of the microsporidians
      were found to infect most of the tissues examined and showed gonadal infection
      and transovarial transmission in the infected silkworms. SSU-rRNA sequence based
      phylogenetic tree placed NIWB-14b, NIWB-12n and NIWB-11bp in a separate branch
      along with other Nosema species and Nosema bombycis; while NIWB-15mb and NIWB
      13md together formed another cluster along with other Nosema species. NIK-1s_mys
      revealed a signature sequence similar to standard type species, N. bombycis,
      indicating that NIK-1s_mys is similar to N. bombycis. Based on phylogenetic
      relationships, branch length information based on genetic distance and nucleotide
      differences, we conclude that the microsporidian isolates identified are
      distinctly different from the other known species and belonging to the genus,
      Nosema. This SSU-rRNA gene sequence analysis method is found to be more useful
      approach in detecting different and closely related microsporidians of this
      economically important domestic insect.

PMID- 23129194
TI  - Molecular genetic studies on morphologically indistinguishable Myxobolus spp.
      infecting cyprinid fishes, with the description of three new species, M.
      alvarezae sp. nov., M. sitjae sp. nov. and M. eirasianus sp. nov.
AB  - While studying Myxobolus gill infections of cyprinid fishes, the authors found
      large, segmented plasmodia in three species: ide (Leuciscus idus), asp (Aspius
      aspius) and white bream (Blicca bjoerkna). As regards their size and morphology,
      the spores from these plasmodia corresponded to those of M. dujardini described
      from chub (Leuciscus cephalus). However, the 18S rDNA sequences of spores from
      the three cyprinids differed from those of M. dujardini. Based on molecular
      differences, this paper describes two new species: M. alvarezae sp. nov. from ide
      and asp, and M. sitjae sp. nov. from white bream. The two new species and M.
      dujardini had a similar tissue tropism, and infected the multilayered epithelium
      of the gill filaments. Histological examination of the infected filaments
      demonstrated that the large plasmodia with multiple buddings were formed from
      amalgamating small plasmodia. Besides carrying infection in the filamental
      epithelium, the three above fish species were infected by small intralamellar
      plasmodia as well. These plasmodia were filled by spores that resembled the roach
      parasite M. intimus both in morphology and seasonal development. The 18S rDNA
      sequences of 'intimus-like' spores from ide and asp differed only in some base
      pairs from spores found in the type host roach, and were identified as belonging
      to M. intimus. The spores found in white bream, however, showed 3.6-5.0%
      difference in DNA sequence from those of M. intimus; therefore, they have been
      described as M. eirasianus sp. nov. The aim of this paper was to demonstrate the
      importance of using molecular methods for separating and identifying
      morphologically corresponding or closely similar Myxobolus spp.

PMID- 23129195
TI  - Mawsonascaris parva sp. nov. (Nematoda: Ascaridida) from the Arabian whipray
      Himantura randalli Last, Manjaji-Matsumoto et Moore (Rajiformes: Dasyatidae) off
      the coast of Iraq.
AB  - Mawsonascaris parva sp. nov. collected from the Arabian whipray Himantura
      randalli Last, Manjaji-Matsumoto et Moore (Rajiformes: Dasyatidae) off the coast
      of Iraq is described and illustrated using light and scanning electron
      microscopy. The new species differs from its congeners by its small body size
      (8.11-18.2 mm long), the absence of an intestinal caecum, the slightly unequal
      spicules (left and right spicule 1.08-2.50 mm and 0.98-2.01 mm long,
      respectively, representing 12.1-13.7% and 10.1-12.1% of body length), the number
      and arrangement of male caudal papillae (13-14 pairs in total, arranged as: 7-8
      pairs of precloacal, 1 pair of double paracloacal and 5 pairs of postcloacal) and
      the presence of a single, median precloacal papilla. Thus, a total of six species
      of Mawsonascaris are now known and this is the first species of this genus
      recorded from species of Himantura.

PMID- 23129196
TI  - Philometroides acanthopagri sp. nov., a new philometrid (Nematoda, Philometridae)
      from the musculature of Acanthopagrus latus (Sparidae) from marine waters of
      Iraq.
AB  - A new nematode species, Philometroides acanthopagri sp. nov. (Philometridae), is
      described from gravid and subgravid specimens found in the musculature near
      pectoral fins and in nasal cavity of the yellowfin seabream Acanthopagrus latus
      (Houttuyn) (Sparidae, Perciformes) from marine waters off the coast of southern
      Iraq. Based on light and scanning electron microscopical examination, the new
      species differs from its congeners in a combination of morphological and
      biometrical features. It is the first species of Philometroides reported from a
      sparid fish and the first representative of this genus recorded from fishes in
      the Arabian Gulf. A key to Philometroides species parasitizing marine and
      brackish-water fishes is provided.

PMID- 23129197
TI  - The bird ectoparasite Dermanyssus hirundinis (Acari, Mesostigmata) in the High
      Arctic; a new parasitic mite to Spitsbergen, Svalbard.
AB  - Ectoparasites are common on birds and in their nests. Amongst these parasites are
      diverse gamasid mite species that can lead to irritation, disease transmission
      and blood loss. Few studies of the ectoparasites of birds breeding in the High
      Arctic exist. The parasitic mite, Dermanyssus hirundinis, was found in nests of
      snow buntings Plectrophenax nivalis nivalis, both natural nests and within
      nesting boxes, on Spitsbergen. Densities per nest varied from sporadic to greater
      than 26,000 individuals. This is the northernmost observation of this parasite.
      The mite was present in new nests, nests constructed the previous year and nests
      not utilized the previous summer. The parasite survives at least 18 months
      without access to a blood meal and can tolerate the Arctic winter, surviving
      temperatures below -20 degrees C. D. hirundinis is hence well adapted to arctic
      conditions. Only females were observed suggesting that this population is
      facultatively parthenogenetic.

PMID- 23129198
TI  - Syringophilopsis davidi sp. nov. (Prostigmata, Syringophilidae) a new quill mite
      species parasitizing Calandrella brachydactyla (Passeriformes, Alaudidae) in
      Egypt.
AB  - A new quill mite species Syringophilopsis davidi sp. nov. (Prostigmata,
      Syringophilidae) parasitizing Greater Short-toed Lark Calandrella brachydactyla
      (Leisler) (Passeriformes, Alaudidae) in Egypt is described. This new species is
      distinguishable from S. tyranni Bochkov and Galloway by 10-13 chambers of the
      peritremal lateral branches, setae se located slightly anterior to c1, and by
      setae ag2 about twice longer than the genital setae. This is the first record of
      this genus from the hosts of the family Alaudidae and in the Arab Republic of
      Egypt.

PMID- 23129199
TI  - Fur mites of the family Listrophoridae (Acariformes: Sarcoptoidea) associated
      with South American sigmodontine rodents (Cricetidae: Sigmodontinae).
AB  - Six species of 3 genera belonging to the fur mite family Listrophoridae were
      recorded on skins of South American rodents of the cricetid subfamily
      Sigmodontinae housed in the Bavarian State Collection of Zoology (Munich,
      Germany). Among them, Amlistrophorus geoxus sp. nov. from Geoxus valdivianus from
      Chile is described as a new for science, and males of Prolistrophorus amazonicus
      amazonicus Fain, 1971 are recorded for the first time. The full generic status
      for the subgenus Amlistrophorus of the genus Prolistrophorus proposed by Fain et
      al. (1996) is not supported, and Prolistrophorus musculinus Fain, 1973 stat. nov.
      (formerly a subspecies of P. amazonicus) from Mus musculus (Rodentia: Muridae)
      from Suriname is raised to species status. New hosts are recorded for the
      following species: Prolistrophorus argentinus (Hirst, 1921) from Holochilus
      brasiliensis and H. chacarius from Argentina, P. amazonicus from Calomys callosus
      from Argentina and Bolivia, C. laucha and C. musculinus from Argentina, P. akodon
      Fain and Lukoschus, 1982 from Akodon montensis from Argentina, P. nectomys Fain,
      1971 from Nectomys palmipes from Peru and Melanomys caliginosus from Panama, and
      Sclerolistrophorus oxymycteris Fain, 1976 from Oryzomys laticeps from Brazil.

PMID- 23129200
TI  - A new species of Aspidophryxus G.O. Sars, 1883 (Crustacea, Isopoda, Dajidae) from
      Caribbean mysid shrimp.
AB  - A new species of dajid isopod in the genus Aspidophryxus G.O. Sars, 1883 is
      described from three females and one male found infesting the lateral carapace of
      Heteromysis (Olivemysis) actiniae Clarke, 1955 (Mysidae: Heteromysinae)
      associated with the corkscrew anemone Bartholomea annulata (Lesuer, 1817)
      (Anthozoa: Aiptasiidae) from the British Virgin Islands. This is the first record
      of the genus from the western Atlantic; three other species are known from
      northern European waters, the central Atlantic and Japan, all on mysid hosts. The
      new species is the first dajid recorded from tropical Caribbean waters. A key to
      species in the genus and a list of all known hosts with parasite orientation are
      provided.

PMID- 23129201
TI  - Molecular identification of Trichinella britovi in martens (Martes martes) and
      badgers (Meles meles); new host records in Poland.
AB  - Trichinella larvae were detected in a marten (Martes martes) and a badger (Meles
      meles) in Poland. The animals were found dead following car accidents. All
      examined animals derived from the Mazurian Lake district, north-east Poland, near
      the village Kosewo Gorne where Trichinella infection were earlier confirmed in
      wildlife; red foxes and wild boars. The muscle samples were examined by
      artificial pepsin-HCl digestion method. The parasites were identified as
      Trichinella britovi by multiplex polymerase chain reaction method. Larvae were
      found in two out of three martens and one out of seven examined badgers. This is
      the first report of the identification of Trichinella britovi larvae from martens
      and badgers in Poland.

PMID- 23129202
TI  - Colloid-electrospinning: fabrication of multicompartment nanofibers by the
      electrospinning of organic or/and inorganic dispersions and emulsions.
AB  - Solution-, melt-, and co-axial electrospinning are well-known methods for
      producing nano- and microfibers. The electrospinning of colloids (or colloid
      electrospinning) is a new field that offers the possibility to elaborate
      multicompartment nanomaterials. However, the presence of colloids in the
      electrospinning feed further complicates theoretical predictions in a system that
      is dependent on chemical, physical, and process parameters. Herein, we give a
      summary of recent important results and discuss the perspectives of
      electrospinning of colloids for the synthesis and characterization of
      multicompartment fibers.

PMID- 23129203
TI  - Demethylesterification of cell wall pectins in Arabidopsis plays a role in seed
      germination.
AB  - The methylesterification status of cell wall homogalacturonans, mediated through
      the action of pectin methylesterases (PMEs), influences the biophysical
      properties of plant cell walls such as elasticity and porosity, important
      parameters for cell elongation and water uptake. The completion of seed
      germination requires cell wall extensibility changes in both the radicle itself
      and in the micropylar tissues surrounding the radicle. In wild-type seeds of
      Arabidopsis (Arabidopsis thaliana), PME activities peaked around the time of
      testa rupture but declined just before the completion of germination (endosperm
      weakening and rupture). We overexpressed an Arabidopsis PME inhibitor to
      investigate PME involvement in seed germination. Seeds of the resultant lines
      showed a denser methylesterification status of their cell wall homogalacturonans,
      but there were no changes in the neutral sugar and uronic acid composition of the
      cell walls. As compared with wild-type seeds, the PME activities of the
      overexpressing lines were greatly reduced throughout germination, and the low
      steady-state levels neither increased nor decreased. The most striking phenotype
      was a significantly faster rate of germination, which was not connected to
      altered testa rupture morphology but to alterations of the micropylar endosperm
      cells, evident by environmental scanning electron microscopy. The transgenic
      seeds also exhibited an apparent reduced sensitivity to abscisic acid with
      respect to its inhibitory effects on germination. We speculate that PME activity
      contributes to the temporal regulation of radicle emergence in endospermic seeds
      by altering the mechanical properties of the cell walls and thereby the balance
      between the two opposing forces of radicle elongation and mechanical resistance
      of the endosperm.

PMID- 23129204
TI  - iRootHair: a comprehensive root hair genomics database.
AB  - The specialized root epidermis cells of higher plants produce long, tubular
      outgrowths called root hairs. Root hairs play an important role in nutrient and
      water uptake, and they serve as a valuable model in studies of plant cell
      morphogenesis. More than 1,300 articles that describe the biological processes of
      these unique cells have been published to date. As new fields of root hair
      research are emerging, the number of new papers published each year and the
      volumes of new relevant data are continuously increasing. Therefore, there is a
      general need to facilitate studies on root hair biology by collecting,
      presenting, and sharing the available information in a systematic, curated
      manner. Consequently, in this paper, we present a comprehensive database of root
      hair genomics, iRootHair, which is accessible as a Web-based service. The current
      version of the database includes information about 153 root hair-related genes
      that have been identified to date in dicots and monocots along with their
      putative orthologs in higher plants with sequenced genomes. In order to
      facilitate the use of the iRootHair database, it is subdivided into interrelated,
      searchable sections that describe genes, processes of root hair formation, root
      hair mutants, and available references. The database integrates bioinformatics
      tools with a focus on sequence identification and annotation. iRootHair is a
      unique resource for root hair research that integrates the large volume of data
      related to root hair genomics in a single, curated, and expandable database that
      is freely available at www.iroothair.org.

PMID- 23129205
TI  - Future CO2-induced ocean acidification mediates the physiological performance of
      a green tide alga.

PMID- 23129206
TI  - Rapid reversion from monomer to dimer regenerates the ultraviolet-B photoreceptor
      UV RESISTANCE LOCUS8 in intact Arabidopsis plants.
AB  - Arabidopsis (Arabidopsis thaliana) UV RESISTANCE LOCUS8 (UVR8) is a photoreceptor
      that specifically mediates photomorphogenic responses to ultraviolet (UV)-B in
      plants. UV-B photoreception induces the conversion of the UVR8 dimer into a
      monomer that interacts with the CONSTITUTIVELY PHOTOMORPHOGENIC1 (COP1) protein
      to regulate gene expression. However, it is not known how the dimeric
      photoreceptor is regenerated in plants. Here, we show, by using inhibitors of
      protein synthesis and degradation via the proteasome, that the UVR8 dimer is not
      regenerated by rapid de novo synthesis following destruction of the monomer.
      Rather, regeneration occurs by reversion from the monomer to the dimer. However,
      regeneration of dimeric UVR8 in darkness following UV-B exposure occurs much more
      rapidly in vivo than in vitro with illuminated plant extracts or purified UVR8,
      indicating that rapid regeneration requires intact cells. Rapid dimer
      regeneration in vivo requires protein synthesis, the presence of a carboxyl
      terminal 27-amino acid region of UVR8, and the presence of COP1, which is known
      to interact with the carboxyl-terminal region. However, none of these factors can
      account fully for the difference in regeneration kinetics in vivo and in vitro,
      indicating that additional proteins or processes are involved in UVR8 dimer
      regeneration in vivo.

PMID- 23129207
TI  - The mitochondrial folylpolyglutamate synthetase gene is required for nitrogen
      utilization during early seedling development in arabidopsis.
AB  - Investigations into the biochemical processes and regulatory mechanisms of
      nitrogen (N) utilization can aid in understanding how N is used efficiently in
      plants. This report describes a deficiency in N utilization in an Arabidopsis
      (Arabidopsis thaliana) transfer DNA insertion mutant of the mitochondrial
      folylpolyglutamate synthetase gene DFC, which catalyzes the conjugation of
      glutamate residues to the tetrahydrofolate during folate synthesis. The mutant
      seedlings displayed several metabolic changes that are typical of plant responses
      to low-N stress, including increased levels of starch and anthocyanin synthesis
      as well as decreased levels of soluble protein and free amino acid, as compared
      with those in wild-type seedlings when external N was sufficient. More striking
      changes were observed when dfc seedlings were grown under N-limited conditions,
      including shorter primary roots, fewer lateral roots, higher levels of glycine
      and carbon-N ratios, and lower N content than those in wild-type seedlings. Gene
      expression studies in mutant seedlings revealed altered transcript levels of
      several genes involved in folate biosynthesis and N metabolism. The biochemical
      and metabolic changes also suggested that N assimilation is drastically perturbed
      due to a loss of DFC function. The observation that elevated CO(2) partly rescued
      the dfc phenotypes suggests that the alterations in N metabolism in dfc may be
      mainly due to a defect in photorespiration. These results indicate that DFC is
      required for N utilization in Arabidopsis and provide new insight into a
      potential interaction between folate and N metabolism.

PMID- 23129208
TI  - Clinical application of circulating tumor cells in breast cancer: overview of the
      current interventional trials.
AB  - In 2004, circulating tumor cells (CTC) enumeration by the CellSearch(r) technique
      at baseline and during treatment was reported to be associated with prognosis in
      metastatic breast cancer patients. In 2008, the first evidence of the impact of
      CTC detection by this technique on survival of cM0(i+) patients were reported.
      These findings were confirmed by other non-interventional studies, whereas CTC
      were also investigated as a surrogate for tumor biology, mainly for HER2
      expression/amplification. The aim of this report is to present the current
      prospective large interventional studies that have been specifically designed to
      demonstrate that CTC enumeration/characterization may improve the management of
      breast cancer patients: STIC CTC METABREAST (France) and Endocrine Therapy Index
      (USA) assess the CTC-guided hormone therapy vs chemotherapy decision in M1
      patients; SWOG0500 (USA) and CirCe01 (France) assess the CTC count changes during
      treatment in metastatic patients; DETECT III (M1 patients, Germany) and Treat CTC
      (cM0(i+) patients, European Organization for Research and Treatment of
      Cancer/Breast International Group) assess the use of anti-HER2 treatments in HER2
      negative breast cancer patients selected on the basis of CTC
      detection/characterization. These trials have different designs in various
      patient populations but are expected to be the pivotal trials for CTC
      implementation in the routine management of breast cancer patients.

PMID- 23129209
TI  - Cooperative spin transition in a mononuclear manganese(III) complex.
AB  - Mind the gap: A complete, cooperative spin transition for a mononuclear Mn(III)
      complex is reported with an 8 K hysteresis window. Raman spectra collected at a
      single temperature in warming and cooling modes confirm the electronic
      bistability within the hysteresis loop. The source of the cooperativity is a
      disconnection in the hydrogen-bonded 1D chains that connect adjacent cations
      owing to an order-disorder transition in the PF(6)(-) counterion.

PMID- 23129210
TI  - Re: dietary supplement use by children and adolescents in the United States to
      enhance sport performance: results of the National Health Interview Survey.

PMID- 23129212
TI  - Mechanisms of subcutaneous absorption of rituximab in rats.
AB  - Absorption of monoclonal antibodies (mAbs) after s.c. injection results from the
      interplay among several kinetic processes. The aims of this study were to
      investigate the absorption mechanisms of rituximab in rats by using slow s.c.
      infusion and coadministration with nonspecific IgG or hyaluronidase, and to
      evaluate the predictive performance of the pharmacokinetic model previously
      developed to describe the nonlinear absorption behavior of mAbs. Rituximab serum
      concentrations were measured after s.c. coadministration with nonspecific IgG and
      hyaluronidase to rats. Several dose levels and different injection sites were
      evaluated. For the back site, 6.5- and 2.6-fold decreases in the area under the
      concentration-time curve were obtained after coadministration with IgG for 1 and
      10 mg/kg doses compared with administration of rituximab alone. For the abdomen,
      only a minor reduction in concentrations was observed. Hyaluronidase increased
      the rate of s.c. absorption and the bioavailability (1.9- and 1.6-fold for the
      back and the abdomen injection of 10 mg/kg). Our previously established
      pharmacokinetic model provided excellent predictions of the effect of nonspecific
      IgG on rituximab absorption. In conclusion, the magnitude of the effect of
      absorption modifiers is dependent on the site of injection and the dose level of
      rituximab. Pharmacokinetic profiles further support the hypothesis that neonatal
      Fc receptor-mediated transport is a major determinant of s.c. absorption of mAbs.

PMID- 23129211
TI  - Hepatobiliary disposition of 17-OHPC and taurocholate in fetal human hepatocytes:
      a comparison with adult human hepatocytes.
AB  - Little information is available in the literature regarding the expression and
      activity of transporters in fetal human liver or cultured cells. A synthetic
      progesterone structural analog, 17alpha-hydroxyprogesterone caproate (17-OHPC),
      is used in the prevention of spontaneous abortion in women with a history of
      recurrent miscarriage (habitual abortion). 17-OHPC has been reported to traverse
      the placental barrier and gain access to fetal circulation. In this study, the
      role of transporters in the disposition of 17-OHPC in fetal and adult human
      hepatocytes was examined. Progesterone metabolites have been reported to induce
      trans-inhibition of bile acid transporter, ABCB11. Thus, we investigated the
      effect of 17-OHPC or its metabolites on [(3)H]taurocholic acid transport in
      sandwich-cultured human fetal and adult hepatocytes. 17-OHPC was taken up rapidly
      into the cells and transported out partially by an active efflux process that was
      significantly inhibited by cold temperature, cyclosporine, verapamil, and
      rifampin. The active efflux mechanism was observed in both adult and fetal
      hepatocyte cultures. 17-OHPC produced a concentration-dependent inhibition of
      taurocholate efflux into canaliculi in sandwich-cultured adult and fetal human
      hepatocytes. However, given the high concentrations required to cause inhibition
      of these transport processes, no adverse effects would be anticipated from
      therapeutic levels of 17-OHPC. We also evaluated the expression of various
      hepatic transporters (ABCB1, ABCB4, SLCO1B1, SLCO1B3, SLCO2B1, ABCB11, SLC10A1,
      ABCC2, ABCC3, ABCC4, and ABCG2) in fetal and adult hepatocytes. With the
      exception of ABCB4, all transporters examined were expressed, albeit at lower
      mRNA levels in fetal hepatocytes compared with adults.

PMID- 23129213
TI  - Prediction of crizotinib-midazolam interaction using the Simcyp population-based
      simulator: comparison of CYP3A time-dependent inhibition between human liver
      microsomes versus hepatocytes.
AB  - Crizotinib (Xalkori) is an orally available potent inhibitor of multiple tyrosine
      kinases, including anaplastic lymphoma kinase and mesenchymal-epithelial
      transition factor. Objectives of the present study were as follows: 1) to
      characterize crizotinib time-dependent inhibition (TDI) potency for CYP3A in
      human liver microsomes (HLM) and cryopreserved human hepatocytes suspended in
      human plasma (HSP); 2) to characterize crizotinib enzyme induction potency on
      CYP3A4 in cryopreserved human hepatocytes; 3) to predict crizotinib steady-state
      plasma concentrations in patients (e.g., autoinhibition and autoinduction) using
      the mechanistic dynamic model, Simcyp population-based simulator; and 4) to
      predict a clinical crizotinib-midazolam interaction using the dynamic model as
      well as the static mathematical model. Crizotinib inactivation constant (K(I))
      and maximum inactivation rate constant (k(inact)) for TDI were estimated as,
      respectively, 0.37 uM and 6.9 h(-1) in HLM and 0.89 uM and 0.78 h(-1) in HSP.
      Thus, crizotinib inactivation efficiency (k(inact)/K(I)) was ~20-fold lower in
      HSP relative to HLM. Crizotinib E(max) and EC(50) for CYP3A4 induction (measured
      as mRNA expression) were estimated as 6.4- to 29-fold and 0.47 to 3.1 uM,
      respectively. Based on these in vitro parameters, the predicted crizotinib steady
      state area under plasma concentration-time curve (AUC) with HLM-TDI was 2.1-fold
      higher than the observed AUC, whereas that with HSP-TDI was consistent with the
      observed result (<=1.1-fold). The increase in midazolam AUC with coadministration
      of crizotinib (21-fold) was significantly overpredicted using HLM-TDI, whereas
      the prediction using HSP-TDI (3.6-fold) was consistent with the observed result
      (3.7-fold). Collectively, the present study demonstrated the value of HSP to
      predict in vivo CYP3A-mediated drug-drug interaction.

PMID- 23129214
TI  - Human adipose CD34+ CD90+ stem cells and collagen scaffold constructs grafted in
      vivo fabricate loose connective and adipose tissues.
AB  - Stem cell based therapies for the repair and regeneration of various tissues are
      of great interest for a high number of diseases. Adult stem cells, instead, are
      more available, abundant and harvested with minimally invasive procedures. In
      particular, mesenchymal stem cells (MSCs) are multi-potent progenitors, able to
      differentiate into bone, cartilage, and adipose tissues. Human adult adipose
      tissue seems to be the most abundant source of MSCs and, due to its easy
      accessibility; it is able to give a considerable amount of stem cells. In this
      study, we selected MSCs co-expressing CD34 and CD90 from adipose tissue. This
      stem cell population displayed higher proliferative capacity than CD34(-) CD90(-)
      cells and was able to differentiate in vitro into adipocytes (PPARgamma(+) and
      adiponectin(+)) and endothelial cells (CD31(+) VEGF(+) Flk1(+)). In addition, in
      methylcellulose without VEGF, it formed a vascular network. The aim of this study
      was to investigate differentiation potential of human adipose CD34(+) /CD90(+)
      stem cells loaded onto commercial collagen sponges already used in clinical
      practice (Gingistat) both in vitro and in vivo. The results of this study clearly
      demonstrate that human adult adipose and loose connective tissues can be obtained
      in vivo, highlighting that CD34(+) /CD90 ASCs are extremely useful for
      regenerative medicine.

PMID- 23129215
TI  - Effects of drought on the microtranscriptome of field-grown sugarcane plants.
AB  - Sugarcane (Saccharum spp.) is the most promising crop for renewable energy. Among
      the diverse stresses that affect plant productivity, drought stress frequently
      causes losses in sugarcane fields. Although several studies have addressed plant
      responses to drought using controlled environments, plant responses under field
      conditions are largely unknown. Recently, microRNA (miRNA)-mediated post
      transcriptional regulation has been described as an important and decisive
      component in vegetal development and stress resistance modulation. The role of
      miRNAs in sugarcane responses to drought under field conditions is currently not
      known. Two sugarcane cultivars differing in drought tolerance were grown in the
      field with and without irrigation (rainfed) for 7 months. By using small RNA deep
      sequencing, we were able to identify 18 miRNA families comprising 30 mature miRNA
      sequences. Among these families, we found 13 mature miRNAs that were
      differentially expressed in drought-stressed plants. Seven miRNAs were
      differentially expressed in both cultivars. The target genes for many of the
      differentially expressed mature miRNAs were predicted, and some of them were
      validated by quantitative reverse transcription PCR. Among the targets, we found
      transcription factors, transporters, proteins associated with senescence, and
      proteins involved with flower development. All of these data increase our
      understanding of the role of miRNAs in the complex regulation of drought stress
      in field-grown sugarcane, providing valuable tools to develop new sugarcane
      cultivars tolerant to drought stress.

PMID- 23129216
TI  - Comparative analysis of barley leaf proteome as affected by drought stress.
AB  - The adaptive response of Egyptian barley land races to drought stress was
      analyzed using difference gel electrophoresis (DIGE). Physiological measurements
      and proteome alterations of accession number 15141, drought tolerant, and
      accession number 15163, drought sensitive, were compared. Differentially
      expressed proteins were subjected to MALDI-TOF-MS analysis. Alterations in
      proteins related to the energy balance and chaperons were the most characteristic
      features to explain the differences between the drought-tolerant and the drought
      sensitive accessions. Further alterations in the levels of proteins involved in
      metabolism, transcription and protein synthesis are also indicated.

PMID- 23129217
TI  - Surface modification of the conducting polymer, polypyrrole, via affinity
      peptide.
AB  - A novel strategy for affinity-based surface modification of the conducting
      polymer, polypyrrole, (PPy), has been developed. A 12-amino acid peptide
      (THRTSTLDYFVI, hereafter denoted T59) was previously identified via the phage
      display technique. This peptide noncovalently binds to the chlorine-doped
      conducting polymer polypyrrole (PPyCl). Studies have previously shown that
      conductive polymers have promising application in neural electrodes, sensors, and
      for improving regeneration and healing of peripheral nerves and other tissues.
      Thus, the strong and specific attachment of bioactive molecules to the surface of
      PPy using the T59 affinity peptide is an exciting new approach to enhance the
      bioactivity of electrically active materials for various biomedical applications.
      We demonstrate this by using T59 as a tether to modify PPyCl with the laminin
      fragment IKVAV to enhance cell interactions, as well as with the so-called
      stealth molecule poly(ethylene glycol; PEG) to decrease cell interactions. Using
      these two modification strategies, we were able to control cell attachment and
      neurite extension on the PPy surface, which is critical for different
      applications (i.e., the goal for tissue regeneration is to enhance cell
      interactions, whereas the goal for electrode and sensor applications is to reduce
      glial cell interactions and thus decrease scarring). Significantly, the
      conductivity of the PPyCl surface was unaffected by this surface modification
      technique, which is not the case with other methods that have been explored to
      surface modify conducting polymers. Finally, using subcutaneous implants, we
      confirmed that the PPyCl treated with the T59 peptide did not react in vivo
      differently than untreated PPyCl.

PMID- 23129218
TI  - Modeling and characterization of inflammatory breast cancer emboli grown in
      vitro.
AB  - Inflammatory breast cancer (IBC) is the deadliest form of breast cancer,
      presenting as intralymphatic emboli. Emboli within the dermal lymphatic vessels
      are thought to contribute to rapid metastasis. The lack of appropriate in vitro
      models has made it difficult to accurately study how IBC emboli metastasize. To
      date, attempts at creating IBC tumor emboli in vitro have used 3D culture on a
      solid layer of Matrigel(TM) , which does not resemble the physical properties of
      the lymphatic system. Dermal lymphatic fluid produces oscillatory fluid shear
      forces and is 1.5-1.7-fold more viscous than water with a pH range of 7.5-7.7. We
      have established a method for forming tumor emboli by culturing the IBC cell
      lines in suspension with either polyethylene glycol- or hyaluronic acid
      containing medium and oscillatory fluid shear forces. Non-IBC cells do not form
      emboli under identical conditions. In vitro IBC emboli were analyzed for
      expression of markers associated with patient emboli and their ability to undergo
      invasion. In a direct comparison, the in vitro IBC emboli closely resemble IBC
      patient emboli with respect to size, composition and E-cadherin expression.
      Further, cells from the emboli are able to invade in clusters via RhoC GTPase
      dependent amoeboid movement. Invasion by clusters of IBC cells is disrupted by
      exposure to TGFbeta. This study provides a biologically relevant in vitro model
      to accurately grow and study inflammatory breast cancer biology and metastasis.

PMID- 23129219
TI  - Overexpression of the prolyl isomerase PIN1 promotes cell growth in osteosarcoma
      cells.
AB  - PIN1 was recently identified as a peptidyl-prolyl cis-trans isomerase (PPIase).
      It binds to and isomerizes specific pSer/Thr-Pro motifs and catalytically induces
      conformational changes after phosphorylation. PIN1 plays an important role in
      several cellular events, such as cell cycle progression, transcriptional
      regulation, RNA processing, cell proliferation and differentiation. The
      relationship between PIN1 and osteosarcoma has not been previously studied. In
      the present study, we investigated the expression pattern of PIN1 in human
      osteosarcoma tissues and the role of PIN1 in osteosarcoma generation and
      development. The expression levels of PIN1 were detected by immunohistochemistry
      and western blotting. Results demonstrated that the expression of PIN1, cyclin D1
      and beta-catenin were significantly higher in human osteosarcoma tissues compared
      to normal tissues. The in vitro effects of PIN1 overexpression were studied in
      human osteosarcoma cell lines. Adenovirus-mediated PIN1 overexpression
      significantly stimulated the proliferation of MG-63 and U2-OS osteosarcoma cells
      by 148+/-10.5 and 187+/-21.5%, respectively. In FACS analysis, U2-OS cells
      displayed significant levels of arrest in cell cycle progression at the G0/G1
      phase. Consistent with increased cell growth, levels of cyclin D1 and cyclin E
      and their associated cyclin-dependent kinases, CDK4 and CDK6, were enhanced in
      PIN1-overexpressed cells compared with the control virus-transfected cells. When
      the PIN1 inhibitor juglone was added to the cells, the proliferative effects of
      PIN1 were abolished. These results suggest that PIN1 may play an important role
      in tumorigenesis and tumor progression of osteosarcoma and therefore, provide a
      new target for gene therapy.

PMID- 23129220
TI  - SNObase, a database for S-nitrosation modification.
AB  - S-Nitros(yl)ation is a ubiquitous redox-based post-translational modification of
      protein cysteine thiols by nitric oxide or its derivatives, which transduces the
      bioactivity of nitric oxide (NO) by regulation of protein conformation, activity,
      stability, localization and protein-protein interactions. These years, more and
      more S-nitrosated proteins were identified in physiological and pathological
      processes and the number is still growing. Here we developed a database named
      SNObase ( http://www.nitrosation.org ), which collected S-nitrosation targets
      extracted from literatures up to June 1st, 2012. SNObase contained 2561
      instances, and provided information about S-nitrosation targets, sites,
      biological model, related diseases, trends of S-nitrosation level and effects of
      S-nitrosation on protein function. With SNObase, we did functional analysis for
      all the SNO targets: In the gene ontology (GO) biological process category, some
      processes were discovered to be related to S-nitrosation ("response to drug",
      "regulation of cell motion") besides the previously reported related processes.
      In the GO cellular component category, cytosol and mitochondrion were both
      enriched. From the KEGG pathway enrichment results, we found SNO targets were
      enriched in different diseases, which suggests possible significant roles of S
      nitrosation in the progress of these diseases. This SNObase means to be a
      database with precise, comprehensive and easily accessible information, an
      environment to help researchers integrate data with comparison and relevancy
      analysis between different groups or works, and also an SNO knowledgebase
      offering feasibility for systemic and global analysis of S-nitrosation in
      interdisciplinary studies.

PMID- 23129221
TI  - Beyond the "central sinus": radiographic findings in patients undergoing revision
      functional endoscopic sinus surgery.
AB  - BACKGROUND: Functional endoscopic sinus surgery (FESS) is widely used by
      otolaryngologists to treat chronic rhinosinusitis (CRS). The sinonasal anatomy
      and pathology found in patients with CRS varies widely, as does the FESS
      technique practiced by otolaryngologists. Variations in the completeness of cell
      group dissection, combined with the technical challenge of angled endoscopy,
      result in a wide variation of the post-FESS cavities harboring persistent
      disease. The purpose of this study was to identify previously incompletely
      dissected anatomic structures associated with mucosal thickening found in
      patients undergoing revision FESS for persistent or recurrent CRS. METHODS:
      Retrospective review of axial, coronal, and sagittal computed tomography (CT)
      scans of patients undergoing revision FESS by 3 fellowship-trained rhinologists
      at a tertiary referral center. RESULTS: The CT scans of 55 patients undergoing
      revision FESS were reviewed. The most frequent radiographic findings were
      residual anterior and posterior ethmoid cells or septations, found in 65% of
      sides and 75% of patients. In addition, residual anterior ethmoid agger nasi
      cells, unopened sphenoid, and residual uncinates were found in 52%, 51%, and 46%
      of sides, respectively. A large percentage of the patients demonstrated residual
      ethmoid cells present on the lamina papyracea and skull base, with a lower number
      found posterior to the middle turbinate basal lamella. A greater number of
      residual right-sided vs left-sided ethmoid cells was noted, with the difference
      being significant (p < 0.05) at the skull base. CONCLUSION: Analysis of CT scans
      of patients undergoing revision FESS for persistent or recurrent CRS frequently
      reveals persistent anatomical structures or incompletely resected cells
      associated with persistent mucosal thickening. Meticulous, complete cell group
      dissection combined with use of angled endoscopy along with identification of
      possible predisposing structures may aid in the reduction of need for revision
      surgery.

PMID- 23129223
TI  - Individually addressable patterned multilayer microchambers for site-specific
      release-on-demand.
AB  - Patterned arrays of light-responsive microchambers are suggested as candidates
      for site-specific release of chemicals in small and precisely defined quantities
      on demand. A composite film is made of poly(allylammonium)-poly(styrene
      sulfonate) multilayers and gold nanoparticles incorporated between subsequent
      stacks of polyelectrolytes. The film shaped as microchambers is loaded with
      colloid particles or oil-soluble molecules. The microchambers are sealed onto a
      glass slide precoated with an adhesive poly(diallyldimethylammonium)-poly(styrene
      sulfonate) multilayer film. A focused laser beam is used for remote addressing
      the individual microchambers and site-specific release of the loaded cargo.

PMID- 23129224
TI  - Anterolateral approach using tibial tubercle osteotomy for total knee
      arthroplasty: can we predict failure?
AB  - PURPOSE: The purpose of this study was to identify predictive factors for the
      occurrence of complications in a consecutive series of patients who underwent
      step-cut tibial tubercle osteotomy (TTO) and subsequent screw refixation in
      primary total knee arthroplasty (TKA). METHODS: Using standardised conventional
      radiographs, critical parameters including TTO length and depth, proximal
      abutment width (OT), and orientation and placement of fixation screws were
      measured in 422 patients (mean age of 71 years and a follow-up time range of one
      to five years) with two screw fixations. RESULTS: Medial spatial orientation in
      the distal screw (11 %, p=0.046), the TTO length (<55.4 mm, p=0.013), the OT
      width (<14 mm, p=0.002) and the distance of the distal refixation screw from the
      TKA (<51.7 mm, p=0.003) were significant factors for the occurrence of
      complications. CONCLUSIONS: Age, gender, comorbidities, height, weight and/or the
      body mass index had no significant influence on the occurrence of complications.
      The TTO-related complication rate was 3 %. Consideration of these key surgical
      factors leads to improved outcomes.

PMID- 23129225
TI  - Can the Surgical Apgar Score predict morbidity and mortality in general
      orthopaedic surgery?
AB  - PURPOSE: The Surgical Apgar Score (SAS) is a simple tally based on intra
      operative heart rate, blood pressure and blood loss; it predicts 30-day major
      postoperative complications and mortality in different surgical fields, but no
      validation has been performed in general orthopaedic surgery. METHODS: A
      prospective assessment of the SAS in 723 consecutive patients undergoing major
      and intermediate orthopaedic procedures was performed in an 18-month period. The
      SAS was calculated immediately after surgery, and the occurrence of major
      complications or death was registered within a 30-day follow-up. RESULTS: Thirty
      seven patients had >=1 complication (5.12 %). The complication rate did not
      augment as the score decreased (SAS 9-10 = 6.56 %; SAS 7-8 = 2.62 %; SAS 5-6 =
      7.21 %; SAS <=4 = 10.2 %), the relative risk did not augment as the score
      decreased and the likelihood ratio did not increase with decreasing SAS values,
      except in the subgroup of patients undergoing spine surgery. The C-statistic was
      0.59 (95 % confidence interval 0.48-0.69), a weak discriminatory value. Using a
      threshold of 7 to define high-risk and low-risk patients, the SAS allowed risk
      stratification only for spine surgery. CONCLUSIONS: The SAS does not predict 30
      day major complications and death in patients undergoing general orthopaedic
      surgery, but it is useful in the subgroup of patients undergoing spine surgery.

PMID- 23129227
TI  - Termite fishing laterality in the Fongoli savanna chimpanzees (Pan troglodytes
      verus): further evidence of a left hand preference.
AB  - Whether nonhuman primates show population-level handedness is a topic of much
      scientific debate. A previous study of handedness for termite fishing reported
      population-level left handedness in the chimpanzees from Gombe National Park,
      Tanzania. In the current study, we examined whether similar hand preferences were
      evident in a savanna-dwelling chimpanzee population with regards to termite
      fishing. Hand preference data were collected for 27 chimpanzees from February
      2007 through July 2008 and November 2011 through January 2012 in southeastern
      Senegal. Overall, the Fongoli chimpanzees demonstrate a trend toward population
      level handedness, though the results did not reach conventional levels of
      statistical significance likely due to the limited sample size. Fongoli
      chimpanzees showed the same pattern of left hand preference as reported at Gombe
      and the two populations did not differ significantly. When the data were combined
      across all studies, wild chimpanzees showed a population-level left hand
      preference for termite fishing.

PMID- 23129228
TI  - Stabilization of the prostate-specific tumor suppressor NKX3.1 by the oncogenic
      protein kinase Pim-1 in prostate cancer cells.
AB  - Loss of NKX3.1 is an early and consistent event in prostate cancer and is
      associated with increased proliferation of prostate epithelial cells and poor
      prognosis. NKX3.1 stability is regulated post-translationally through
      phosphorylation at multiple sites by several protein kinases. Here, we report the
      paradoxical stabilization of the prostate-specific tumor suppressor NKX3.1 by the
      oncogenic protein kinase Pim-1 in prostate cancer cells. Pharmacologic Pim-1
      inhibition using the small molecule inhibitor CX-6258 decreased steady state
      levels and half-life of NKX3.1 protein but mRNA was not affected. This effect was
      reversed by inhibition of the 26S-proteasome, demonstrating that Pim-1 protects
      NKX3.1 from proteasome-mediated degradation. Mass spectrometric analyses revealed
      Thr89, Ser185, Ser186, Ser195, and Ser196 as Pim-1 phospho-acceptor sites on
      NKX3.1. Through mutational analysis, we determined that NKX3.1 phosphorylation at
      Ser185, Ser186, and within the N-terminal PEST domain is essential for Pim-1
      mediated stabilization. Further, we also identified Lys182 as a critical residue
      for NKX3.1 stabilization by Pim-1. Pim-1-mediated NKX3.1 stabilization may be
      important in maintaining normal cellular homeostasis in normal prostate
      epithelial cells, and may maintain basal NKX3.1 protein levels in prostate cancer
      cells.

PMID- 23129230
TI  - Enzyme-responsive controlled release of covalently bound prodrug from functional
      mesoporous silica nanospheres.
AB  - I want to break free: Mesoporous silica nanoparticles are functionalized with
      sulfasalazine (SZ; see scheme), a prodrug of 5-aminosalicylic acid (5-ASA) and
      sulfapyridine, to generate enzyme-responsive nanocarriers. In the presence of the
      colon-specific enzyme azo-reductase (orange), 5-ASA and sulfapyridine are
      efficiently released.

PMID- 23129231
TI  - Temporal distribution of p300/CBP immunoreactivity in the adult rat spinal dorsal
      horn following chronic constriction injury (CCI).
AB  - p300 and its homolog cyclic AMP response element binding protein (CBP) are
      coactivators that were identified to participate in many biological processes
      including neural development and cognition. Their roles within the rodent spinal
      cord have not been reported systematically; in this study, their spatiotemporal
      distribution in the spinal cord of adult rat following chronic constriction
      injury (CCI) was studied. p300 and CBP expressed predominantly in nuclei in the
      gray matter of rat spinal cord. Rats undergoing CCI surgery showed increased
      p300/CBP immunoreactivity (IR) compared with normal control and sham-operated
      rats. The number of IR cells reached the peak at day 14 following CCI compared
      with those on day 3, 7, and 21, accompanied with significant behavioral changes
      of neuropathic pain. Cell-type determination by immunofluorescence at day 14
      following CCI revealed that p300 and CBP expressed in neurons, but not in
      astrocytes or microglial cells. These results suggest that p300 and CBP are
      probably involved in the maintenance of neuropathic pain on spinal cord level.
      Furthermore, p300 and CBP may serve as a sensor only in neurons but not in
      astrocytes or microglia cells in the adult rat spinal cord.

PMID- 23129233
TI  - A 13-week toxicity study of acrylamide administered in drinking water to
      hamsters.
AB  - Acrylamide (AA) is known to induce tumors in various organs/tissues in rats and
      mice. Epidemiological studies of oral exposure have generated controversial
      results but mortality studies of people who work with AA have indicated increased
      rates of pancreatic cancer. In the present study, for dose selection for chronic
      toxicity/carcinogenicity studies, 13-week toxicity of AA was evaluated in Syrian
      hamsters, which are sensitive to induction of pancreatic ductal carcinogenesis,
      at concentrations required to provide doses of 0 (control), 20, 30 and 50 mg kg(
      1) body weight in drinking water. Treatment with AA caused abnormal gait
      advancing to hind limb paralysis in all males and females at 50 mg kg(-1). Body
      weights in 30 and 50 mg kg(-1) males and 50 mg kg(-1) females were lower than in
      the controls. At termination of the study, red blood cells (RBC) and hemoglobin
      (Hb) were decreased or showed a tendency for a decrease at 20 and 30 mg kg(-1) in
      females. Microscopically, axonal/myelin degeneration of sciatic nerves was
      observed in all AA-treated groups with dose dependence. No obvious changes were
      found in pancreatic ducts/ductules in any groups of animal. These results
      indicated the maximum tolerated dose for long-term studies of AA to be 20 mg kg(
      1) or less in both male and female Syrian hamsters.

PMID- 23129232
TI  - Temporal-spatial expressions of Spy1 in rat sciatic nerve after crush.
AB  - As a novel cell cycle protein, Spy1 enhances cell proliferation, promotes the
      G1/S transition as well as inhibits apoptosis in response to UV irradiation. Spy1
      levels are tightly regulated during mammary development, and overexpression of
      Spy1 accelerates tumorigenesis in vivo. But little is known about the role of
      Spy1 in the pathological process of damage and regeneration of the peripheral
      nervous system. Here we established a rat sciatic nerve crush (SNC) model to
      examine the spatiotemporal expression of Spy1. Spy1 expression was elevated
      gradually after sciatic nerve crush and peaked at day 3. The alteration was due
      to the increased expression of Spy1 in axons and Schwann cells after SNC. Spy1
      expression correlated closely with Schwann cells proliferation in sciatic nerve
      post injury. Furthermore, Spy1 largely localized in axons in the crushed segment,
      but rarely co-localized with GAP43. These findings suggested that Spy1
      participated in the pathological process response to sciatic nerve injury and may
      be associated with Schwann cells proliferation and axons regeneration.

PMID- 23129234
TI  - "Sinus headache": rhinogenic headache or migraine? An evidence-based guide to
      diagnosis and treatment.
AB  - BACKGROUND: Patients present to physicians across multiple disciplines with the
      complaint of sinus headache. This lay term is widely accepted in the media, yet
      has been repeatedly questioned in the medical literature, and experts in the
      fields of otolaryngology, neurology, and allergy have agreed that it is an
      overused and often incorrect diagnosis in the majority of patients. There have
      been review articles and consensus panels established regarding this issue, but
      thus far no guidelines based purely on a review of the level of evidence provided
      by the literature. METHODS: A systematic review of the literature was performed
      and the Clinical Practice Guideline Manual, Conference on Guideline
      Standardization (COGS), and the Appraisal of Guidelines and Research Evaluation
      (AGREE) instrument recommendations were followed. Study inclusion criteria were:
      adult population >18 years old, self-diagnosed or physician-diagnosed "sinus
      headache," clearly defined diagnostic criteria in diagnostic studies, and clearly
      defined primary clinical end-point in therapeutic studies. RESULTS: We identified
      and evaluated the literature on diagnosing and treating patients with a primary
      complaint of sinus headache. The literature was reviewed for both quality of
      research design as well as benefit and harm of the proposed interventions.
      CONCLUSION: If a thorough neurologic and otolaryngologic evaluation is performed,
      the majority of patients presenting with sinus headache in the absence of
      significant acute inflammatory findings will be diagnosed with migraine. In this
      situation, the appropriate treatment for the majority of patients presenting with
      sinus headache is migraine directed therapy. In a highly select group of
      patients, directed nasal surgery addressing endonasal contact points may be an
      option.

PMID- 23129235
TI  - Longitudinal differences in the mechanical properties of the thoracic aorta
      depend on circumferential regions.
AB  - Understanding the mechanical behavior of the arterial wall and its spatial
      variations is essential for the study of vascular physiopathology and the design
      of biomedical devices that interact with the arterial wall. Although it is
      generally accepted that the aortic wall gets stiffer along its length, the
      spatial variations in the mechanical behavior of the thoracic aorta are not well
      understood. In this study, therefore, we investigate both longitudinal and
      circumferential variations in the mechanical properties of the porcine descending
      thoracic aorta. Using a previously developed experimental method and stress
      strain analysis, the stress, stretch, tangent modulus (TM), and pressure-strain
      elastic modulus (PSEM) are estimated in the range of in vivo pressure. The
      results show that the longitudinal differences of both TM and PSEM are
      statistically significant in the posterior region but not in the anterior region.
      Both moduli are greater in the posterior distal region when compared with the
      other test regions. The findings of this study meet a need for clarifying the
      region investigated, especially in circumferential region, to study the regional
      variations in biomechanics of blood vessels.

PMID- 23129236
TI  - Unexpected changes in the gastric remnant in asymptomatic patients after Roux-en
      Y gastric bypass on vertical banded gastroplasty.
AB  - BACKGROUND: The aims of this study are to evaluate the macroscopic and
      microscopic changes in the remnant stomach at mid-term follow-up of patients who
      underwent a Roux-en-Y gastric bypass on vertical banded gastroplasty (RYGB-on
      VBG). The stomach could be reached through a 1.1-cm gastro-gastrostomy with an
      endoscope of standard size. METHODS: From January 2009 to July 2010, 51
      asymptomatic patients at 4 and 5 years follow-up after RYGB-on-VBG submitted to
      upper endoscopy. All of them were examined with standard endoscopy with
      collection of biopsies in gastric fundus, body, and antrum. The macroscopic and
      microscopic findings were analyzed according to Sydney Classification. RESULTS:
      The endoscopy of the remnant stomach was technically easy and already showed on
      macroscopic examination 90 % cases of gastritis (41.2 % mild, 49 % severe) with
      tendency of severity in the distal stomach part. Histological analysis detected
      39.2 % of active gastritis, 50.6 % of quiescent gastritis, 7.8 % of intestinal
      metaplasia, and 3.9 % of lymphoma-like gastritis. CONCLUSIONS: The results
      surprised us. We found a very high rate of mucosa abnormalities after RYGB-on
      VBG. All of the patients have to be regularly controlled in follow-up and
      treatment has to be introduced when needed. Again, we would like to ask the
      question: what is happening with the remnant stomach after standard RYGB, banded
      gastric bapass, or minigastric bypass? Did we reach the time to answer the
      question?

PMID- 23129237
TI  - Jolkinolide B induces apoptosis in MCF-7 cells through inhibition of the
      PI3K/Akt/mTOR signaling pathway.
AB  - The aim of this study was to explore the molecular mechanisms of jolkinolide B
      (JB), which is extracted from the root of Euphorbia fischeriana Steud. In this
      study, we found that JB, a diterpenoid from the traditional Chinese medicinal
      herb, strongly inhibited the PI3K/Akt/mTOR signaling pathway. Furthermore, we
      evaluated the effects of JB on the proliferation and apoptosis of MCF-7 human
      breast cancer cells. Our results showed significant induction of apoptosis in MCF
      7 cells incubated with JB. The viability of the MCF-7 cells was assessed by MTT
      assay. Flow cytometry was used to detect apoptosis and cell cycle analysis.
      Transmission electron microscopy (TEM) analysis was used to observe cell
      morphology. MCF-7 cells were subcutaneously inoculated into nude mice to study
      the in vivo antitumor effects of JB. The growth of MCF-7 cells was inhibited and
      arrested in the S phase by JB. The data showed significantly decreased tumor
      volume and weight in nude mice inoculated with MCF-7 cells. In addition,
      treatment with JB was able to induce downregulation of cyclinD1, cyclinE, mTOR, p
      PI3K and p-Akt, and upregulation of PTEN and p-eIF4E. Collectively, JB-induced
      apoptosis of MCF-7 cells occurs through the PI3K/Akt/mTOR signaling pathway.
      Furthermore, the PI3K/Akt signaling cascade plays a role in the induction of
      apoptosis in JB-treated cells. These observations suggest that JB may have
      therapeutic applications in the treatment of cancer.

PMID- 23129238
TI  - A pictorial review of acute aortic syndrome: discriminating and overlapping
      features as revealed by ECG-gated multidetector-row CT angiography.
AB  - BACKGROUND: The term "acute aortic syndrome" (AAS) encompasses a spectrum of life
      threatening conditions characterized by acute aortic pain. AAS traditionally
      embraces three abnormalities including classic aortic dissection, intramural
      haematoma, and penetrating atherosclerotic ulcer. Although the underlying
      etiologies and conditions predisposing to AAS are diverse, the clinical features
      are indistinguishable. METHODS: Multidetector-row computed tomography (CT) with
      electrocardiographic gating (ECG-gated MDCT) has greatly improved imaging of
      acute thoracic aortic diseases by virtually eliminating pulsation artifacts
      transmitted from cardiac motion and reveals subtle aortic abnormalities, which
      have been difficult to recognize by conventional non-gated CT. RESULTS: While
      these advances in imaging technology provide additional discriminating features
      of acute aortic diseases, they also reveal a range of overlapping features of
      these life-threatening conditions that not uncommonly are dynamic and evolving.
      These overlapping and transitional features may be a major source of
      misunderstanding, confusion, and controversy for diseases that cause AAS.
      CONCLUSION: In this pictorial review, we describe the discriminating and typical
      imaging features as revealed by modern ECG-gated MDCT angiography. In addition to
      the discriminating features, recognition of the overlapping and transitional
      features in AAS will allow a more comprehensive understanding of their underlying
      pathophysiologic conditions and their natural history, and may improve
      therapeutic management. MAIN MESSAGES: * The superior visualization of ECG-gated
      CTA improves the diagnostic accuracy of acute aortic syndrome. * ECG-gated CTA
      provides discriminating features of underlying pathophysiologic conditions of
      AAS. * Also, recognition of the overlapping features in AAS will allow a more
      comprehensive understanding.

PMID- 23129239
TI  - New insights in wound response and repair of epithelium.
AB  - Epithelial wounds usually heal relatively quickly, but repair may be impaired by
      environmental stressors, such as hypoxic or diabetic states, rendering patients
      vulnerable to a number of corneal pathologies. Though this response appears
      simple, at first, years of research have uncovered the complicated biochemical
      pathways coordinating the wound healing response. Here, we investigate signaling
      cascades and individual proteins involved in the corneal epithelium's self
      repair. We will explore how an epithelial cell migrates across the wound bed and
      attaches itself to its new post-injury surroundings, including its neighboring
      cells and the basement membrane, through focal adhesions and hemidesmosomes. We
      will also discuss how the cell coordinates this motion physiologically, through
      calcium signaling and protein phosphorylation, focusing on the communication
      through purinergic, glutamatergic, and growth factor receptors. Many of these
      aspects reflect and can be extended to similar epithelial surfaces, and can be
      used to facilitate wound healing in patients with various underlying pathologies.
      The collective library of laboratory and clinical research done around the world
      has demonstrated how important precise regulation of these processes is in order
      for the injured corneal epithelium to properly heal.

PMID- 23129240
TI  - Developing a short-form structured diagnostic interview for common mental
      disorders using signal detection theory.
AB  - Diagnostic instruments must be relatively free from respondent burden and cost
      effective to administer whilst remaining faithful to the psychiatric
      nomenclature. It seems logical to develop short-form alternatives to rather
      lengthy and complicated diagnostic interviews to facilitate large scale data
      collection. The current study examines one method, signal detection theory, for
      developing a short-form interview based on the Composite International Diagnostic
      Interview version 3.0. The method was able to retain the smallest number of items
      to predict a lifetime and 30 day DSM-IV diagnosis for 10 disorders. Concordance
      analyses between the full-form and the short-form modules, demonstrated an
      excellent level of agreement in the whole sample and various subsamples of the
      Australian population as well as in an international comparison sample of the US
      population. The good concordance between the long form and the short form
      demonstrates the ability of signal detection theory to assist in the development
      of valid short forms, which could replace lengthy diagnostic interviews when the
      aim is to reduce respondent burden and overall research costs.

PMID- 23129241
TI  - Using four capitals to assess watershed sustainability.
AB  - The La Antigua watershed drains into the Gulf of Mexico and can be considered as
      one of the most important areas in Mexico because of its high productivity,
      history, and biodiversity, although poverty remains high in the area in spite of
      these positive attributes. In this study, we performed an integrated assessment
      of the watershed to recommend a better direction toward a sustainable management
      in which the four capitals (natural, human, social, and built) are balanced. We
      contrasted these four capitals in the municipalities of the upper, middle and
      lower watershed and found that natural capital (natural ecosystems and ecosystem
      services) was higher in the upper and middle watershed, while human and social
      capitals (literacy, health, education and income) were generally higher
      downstream. Overall, Human Development Index was negatively correlated with the
      percentage of natural ecosystems in the watershed, especially in the upper and
      lower watershed regions. Our results indicate that natural capital must be fully
      considered in projections for increasing human development, so that natural
      resources can be preserved and managed adequately while sustaining
      intergenerational well-being.

PMID- 23129242
TI  - The prevalence of incontinence in people with cognitive impairment or dementia
      living at home: a systematic review.
AB  - AIMS: To investigate the prevalence of urinary and fecal incontinence in people
      with cognitive impairment or dementia, living at home. METHOD: We searched
      electronic databases, MEDLINE, EMBASE, CINAHL, PsycINFO, BNI, and the Cochrane
      Library (including DARE, NTIS), from January 1, 1990 to 2012 week 13 (April 4)
      for studies reporting prevalence data of urinary and fecal incontinence in the
      population of interest. Quality assessments of studies considered risk of bias in
      criteria for prevalence studies. Due to the heterogeneity of the included study
      populations and results, meta-analysis was not appropriate and a narrative
      analysis was undertaken. RESULTS: From 427 references, eight studies met the
      inclusion criteria. Seven studies provided prevalence rates as findings
      incidental to their primary question. Populations and assessment tools were
      varied. Reported prevalence of urinary incontinence ranged from 1.1% in a general
      community population to 38% in those receiving home care services. Reported rates
      of fecal incontinence were from 0.9% in a community population to 27% in a
      population attending an old age psychiatry outpatient clinic. CONCLUSIONS: The
      prevalence of incontinence in people with dementia or cognitive impairment living
      at home has not been clearly established. Population level data is required to
      inform clinicians and to reliably underpin decision-making in service planning,
      resource allocation and interventions for people with dementia and incontinence.

PMID- 23129244
TI  - New functions of protein kinase Gcn2 in yeast and mammals.
AB  - The classical role of the conserved Gcn2 kinase of yeast and mammals is to
      activate the translation of the transcription factors Gcn4 in yeast and
      activating transcription factor 4 in mammals by phosphorylating the eukaryotic
      translation initiation factor 2alpha. Gcn2 is activated by uncharged tRNAs in
      response to amino acid starvation and this regulatory system is important for
      tolerance to nutrient deprivation and other stresses and for development,
      differentiation, and normal function of mammalian organs. In the past few years,
      the classical Gcn2 pathway has been shown to modulate life span, tumor cell
      survival, and immune responses. In addition, Gcn2 modulates translation of novel
      mRNAs such as those of an unknown regulator of leucine transport and of
      sulfiredoxin SRX1 in yeast (activation of translation) and of inducible nitric
      oxide synthase, ErBb2, HIF1a, and 5'-terminal oligopyrimidine tract mRNAs in
      mammals (inhibition of translation). Finally, Gcn2 directly phosphorylates novel
      proteins such as methionyl-tRNA synthetase in mammals, and this triggers a
      pathway for DNA repair. These findings anticipate many expanding roles of Gcn2 in
      the future, with relevance for stress responses and human disease.

PMID- 23129245
TI  - Transition-metal-free alkoxycarbonylation of aryl halides.
AB  - Transitions: The title reaction has been developed for the synthesis of a variety
      of tert-butyl benzoates by employing 1,10-phenanthroline as an additive. Various
      functional groups were tolerated and heteroaryl iodides were also suitable
      substrates. Preliminary mechanism studies were conducted and indicate the
      participation of radical intermediates.

PMID- 23129246
TI  - Silently waiting to heal: experiences among women living with urinary
      incontinence in northwest Ethiopia.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of this study was to gain in-depth knowledge
      of women suffering from urinary incontinence (UI) in rural and semiurban settings
      in Ethiopia. METHODS: A qualitative study based on semistructured in-depth
      interviews with 26 informants, 18 of whom were women experiencing the symptom of
      urinary leakage. The study was conducted in the Amhara Region of northwest
      Ethiopia and was part of the Dabat Incontinence and Prolapse (DABINCOP) study.
      RESULTS: Limited access to water, soap, pads, and spare clothes characterized
      daily management of the symptom. The consequences for marital relationships and
      social life were of great concern to the informants. Shame, embarrassment, and
      fear of being discriminated against led to huge efforts to hide the leakage.
      Among informants who were not able to hide it, humiliating comments and
      discriminatory behavior were commonly experienced, sometimes leading to divorce
      and self-isolation. Women who disclosed their symptom usually had a person who
      supported them. Women with UI regarded it as unnatural and uncommon. Most took no
      action to improve the situation, as they saw no options for help. CONCLUSIONS:
      Several circumstances limited the opportunities available to women to keep
      themselves clean, disclose the problem to others, and access health information
      and health-care facilities. In order to understand how women in this setting
      practically handled, perceived, and experienced living with UI, it was essential
      to address contextualized and sociocultural dimensions related to the symptom.

PMID- 23129247
TI  - Effectiveness of intravesical hyaluronic acid with or without chondroitin sulfate
      for recurrent bacterial cystitis in adult women: a meta-analysis.
AB  - INTRODUCTION AND HYPOTHESIS: Glycosaminoglycan hyaluronic acid (HA) and
      chondroitin sulphate (CS) protect the urothelium. Damage to the urothelium may
      increase bacterial adherence and infection risk. This meta-analysis evaluated the
      effect of intravesical HA and HA and CS (HA-CS) combination therapy in recurrent
      bacterial cystitis (RBC) in adult women. METHODS: A systematic literature search
      was performed. Primary outcomes were urinary tract infection (UTI) rate per
      patient-year, and UTI recurrence time (days). Secondary outcomes were 3-day voids
      and Pelvic Pain and Urgency/Frequency (PUF) symptom scale total score. RESULTS:
      Four studies involving a total of 143 patients were retrieved and assessed in
      this analysis. Two were randomized, and two were nonrandomized. A significantly
      decreased UTI rate per patient-year [mean difference (MD) -3.41, 95 % confidence
      interval (CI) -4.33 to -2.49, p < 0.00001) was found. Similarly, pooled analysis
      showed a significantly longer mean UTI recurrence time (days) using either HA or
      HA-CS therapy (MD 187.35, 95 % CI 94.33-280.37, p < 0.0001). Two studies using HA
      and HA-CS therapy reported outcomes on 3-day voids, which were not significantly
      improved after therapy (MD -3.59, 95 % CI -8.43-1.25, p = 0.15), but a
      significantly better PUF total score (MD -7.17, 95 % CI -9.86 to -4.48, p <
      0.00001) was detected in HA-CS groups. CONCLUSIONS: Intravesical HA and HA-CS in
      combination significantly reduced cystitis recurrence, mean UTI recurrence time,
      and PUF total score. Study limitations include the small number of patients and
      possible bias. Further studies are needed to validate this promising treatment
      modality.

PMID- 23129248
TI  - Traditional native tissue vs mesh-augmented pelvic organ prolapse repairs:
      providing an accurate interpretation of current literature. Comment.

PMID- 23129249
TI  - Cross-cultural findings on community violence exposure and internalizing
      psychopathology: comparing adolescents in the United States, Russia, and Belgium.
AB  - The study aimed to investigate cross-cultural differences in the relation between
      community violence and psychopathology. A self-report survey was conducted in a
      representative sample of 3,309 14-17 year old adolescents from urban communities
      in the US (N = 1,343), Belgium (N = 946) and Russia (N = 1,009). In all three
      countries, boys reported higher prevalences of violence exposure and more
      victimization by community violence than girls. Controlling for involvement in
      antisocial behavior, levels of psychopathology increased along with severity of
      exposure to community violence (from no exposure to witnessing to victimization).
      The associations between community violence and internalizing problems were
      similar across countries and gender. Current findings suggest that the
      relationships between community violence and adolescent mental health are not
      culture bound and that they follow similar dynamics in different populations.
      Clinical implications and directions are discussed. 

PMID- 23129251
TI  - A test of adolescent internalizing and externalizing symptoms as prospective
      predictors of type of trauma exposure and posttraumatic stress disorder.
AB  - The present study utilized longitudinal data from a high-risk community sample (N
      = 377; 166 trauma-exposed; 202 males; 175 females; 73% non-Hispanic Caucasian) to
      test pretrauma measures of adolescent internalizing and externalizing symptoms as
      unique prospective predictors of type of trauma exposure and PTSD over and above
      the influence of correlated family adversity (a composite of family conflict,
      stress, and parental psychopathology). Data were analyzed with logistic and
      multinomial logistic regressions. Results indicated that females, but not males,
      with higher levels of internalizing (OR = 2.91) and externalizing (OR = 2.37)
      symptoms during adolescence were significantly more likely to be exposed to
      assaultive violence (over and above family adversity). In fact, males with higher
      levels of internalizing symptoms were significantly less likely to be exposed to
      assaultive violence (OR = 0.54). Neither internalizing nor externalizing symptoms
      uniquely predicted exposure to traumatic events that did not involve assaultive
      violence. Among trauma-exposed participants, the unique association between
      internalizing symptoms and later PTSD yielded an odds ratio of 1.79 (p = .07)
      over and above the influences of family adversity, type of trauma exposure, and
      gender. Assaultive violence exposure fully mediated the association between
      females' externalizing symptoms and future PTSD. Findings may help inform the
      prevention of both assaultive violence exposure and PTSD.

PMID- 23129250
TI  - Ideomotor perception modulates visuospatial cueing.
AB  - The ideomotor theory of action posits that the cognitive representation of an
      action includes the learned perceptual effects of the action. Support for this
      theory has come from studies demonstrating how perceptual features that match the
      outcome of a response can facilitate selection of that response. We investigated
      another, complementary implication of ideomotor theory: would a bias toward
      selecting a response result in a perceptual bias toward the known effect of the
      response? In other words, would an action tendency direct attention to the
      anticipated perceptual features? Through an initial acquisition phase,
      participants learned that two possible responses (left/right keypress)
      consistently produced two distinct colors. Next, in a test phase, we manipulated
      response bias at the beginning of each trial, using an uninformative spatial
      prime presented at the left or right periphery. We then examined the extent to
      which color transients that either matched or mismatched the induced response
      bias can orient participants' visual attention. Results revealed a perceptual
      bias toward the color effect of the primed response, manifested in a stronger
      visual orienting toward this color. Thus, biasing response selection can bias
      perception. These findings extend the scope of the ideomotor theory to visual
      perceptual processes. 

PMID- 23129252
TI  - Developmental disorders and altered gene expression in the tropical clawed frog
      (Silurana tropicalis) exposed to 17alpha-ethinylestradiol.
AB  - Several endocrine-disrupting chemicals with estrogenic activity can affect sexual
      development and reproduction in aquatic wildlife. The occurrence of oocytes in
      the testis (testis-ova) is one reproductive disorder and can be used as a valid
      endpoint when studying disruptive effects of estrogenic chemicals. To elucidate
      the molecular basis of testis-ova induction, we conducted gene expression
      analysis in the gonads of Silurana tropicalis exposed to 0, 3, 10 and 30 ng l(-1)
      17alpha-ethinylestradiol (EE2) from 2 days after fertilization to the juvenile
      stage (14 weeks after fertilization). The frequencies of testis-ova induction or
      male to female sex-reversal of the gonads increased in an EE2 dose-dependent
      manner. Microarray analysis showed that expressions of a large number of genes
      were significantly changed by EE2 exposure. Genes including egg envelope
      composition (zp4, zpax, zpc, zp3.2 and egg cortical granule lectin), 42S particle
      genes (42Sp50, 42Sp43 and 42Sp48) and regulation of female germ cells (figla) are
      associated with the testis-ova and sex-reversal situation in the gonads. Of
      those, expression of zpc and 42Sp50 genes is associated with testis-ova. Thus, we
      propose that these genes are useful biomarkers for toxicological research in
      amphibians developmentally exposed to estrogenic chemicals.

PMID- 23129253
TI  - The aerodynamics of the sinonasal interface: the nose takes wing-a paradigm shift
      for our time.
AB  - BACKGROUND: Ventilation of and gas exchange between the nose and the paranasal
      sinuses are believed to occur by convection and diffusion based on experiments
      that neglect the effects of physiological respiration and aerodynamic forces at
      the sinonasal interface (SNI). Based on these experiments, the exchange of gas is
      presumed to be slow, and principally dependent on gas concentration and diameter,
      number, and location of ostia. METHODS: In 12 healthy adult volunteers, real-time
      sinus nitric oxide measurements were obtained with catheters placed through
      natural ostia during respiratory maneuvers. RESULTS: The nose is a masterful
      collection of aerodynamic foils and channels designed to accomplish powered
      sinonasal gas exchange and ventilation within a few seconds during each
      inspiration. CONCLUSION: The new perspective on the functional anatomy of the SNI
      demands a paradigm shift that is followed by physiological, medical, and surgical
      implications and a radical change in our perception and understanding.

PMID- 23129254
TI  - Characterization of hyaluronan-methylcellulose hydrogels for cell delivery to the
      injured spinal cord.
AB  - No effective clinical treatment currently exists for traumatic spinal cord
      injury. Cell replacement therapy holds promise for attaining functional repair.
      Cells may be delivered directly or near the injury site; however, this strategy
      requires a delivery vehicle to maintain cell viability. We have identified an
      injectable, biocompatible, and biodegradable hydrogel scaffold composed of
      hyaluronan (HA) and methylcellulose (MC) that may be an effective scaffold for
      therapeutic cell delivery. The purpose of the present study was to determine the
      effects of polymer concentration on HAMC mechanical strength, gelation time, and
      cell viability. The yield stress of HAMC, a measure of mechanical stiffness, was
      tunable via manipulation of MC and HA content. Measurement of the elastic and
      storage moduli as functions of time revealed that HAMC gels in less than 5 min at
      physiological temperatures. Human umbilical tissue-derived cells encapsulated in
      HAMC were homogenously and stably distributed over 3 days in culture and extended
      processes into the scaffold. Cell viability was stable over this period in all
      but the most concentrated HAMC formulation. Because of its strength-tunability,
      rapid gelation, and ability to maintain cell viability, HAMC is a promising
      vehicle for cell delivery and is being tested in ongoing in vivo studies.

PMID- 23129255
TI  - CLA reduces inflammatory mediators from A427 human lung cancer cells and A427
      conditioned medium promotes differentiation of C2C12 murine muscle cells.
AB  - Conjugated linoleic acid (CLA) is thought to have anti-proliferative and anti
      inflammatory properties, but its effect on cancer cachexia is unknown. Two
      effects were here investigated: that of CLA on inflammatory mediator production
      in human lung cancer cells, and that of reduced mediators on the myogenic
      differentiation of murine muscle C2C12 cells. The latter cells were grown in
      medium conditioned by human lung cancer A427 cells, with or without CLA, to mimic
      only the effect of molecules released from the tumor "in vivo", excluding the
      effect of host-produced cachectic factors. The results obtained show that CLA was
      found to reduce the production of tumor necrosis factor-alpha, interleukin (IL)
      1beta and prostaglandin E2 (PGE2), but had no effect on IL-6 production. The
      mechanisms underlying the effect of CLA on cytokine or PGE2 release in A427 cells
      are probably mediated by activation of peroxisome proliferator-activated receptor
      (PPAR)alpha, which increased at 24 h CLA treatment. In turn, the reduced content
      of inflammatory mediators in medium conditioned by A427 cells, in the presence of
      CLA, allowed muscle cells to proliferate, again by inducing PPAR. The involvement
      of PPARalpha was demonstrated by treatment with the antagonist MK-886. The
      findings demonstrate the anti-inflammatory and myogenic action of CLA and point
      to its possible application as a novel dietary supplement and therapeutic agent
      in inflammatory disease states, such as cachexia.

PMID- 23129256
TI  - How selected tissues of lactating holstein cows respond to dietary
      polyunsaturated fatty acid supplementation.
AB  - The effect of a 10-week supplementation with polyunsaturated fatty acids [via
      sunflower oil/DHA-rich algae (SUNA) or linseed oil/DHA-rich algae (LINA) enriched
      diets] versus saturated fatty acids (SAT) of lactating German Holstein dairy cows
      in mid-lactation on expression patterns of lipid metabolism-associated genes and
      gene products in hepatic, longissimus muscle and subcutaneous/perirenal/omental
      adipose tissue was assessed. Most pronounced transcriptomic responses to dietary
      PUFA were obtained in hepatic [down-regulated ACACA (FC = 0.83, SUNA; FC = 0.86,
      LINA), FADS1 (FC = 0.60, SUNA; FC = 0.72, LINA), FADS2 (FC = 0.64, SUNA; FC =
      0.79, LINA), FASN (FC = 0.64, SUNA; FC = 0.72, LINA), SCD (FC = 0.37, SUNA; FC =
      0.47, LINA) and SREBF1 (FC = 0.79, SUNA, LINA) expression] and omental adipose
      [up-regulated ACACA (FC = 1.58, SUNA; FC = 1.22, LINA), ADFP (FC = 1.33, SUNA; FC
      = 1.32, LINA), CEBPA (FC = 1.75, SUNA; FC = 1.40, LINA), FASN (FC = 1.57, SUNA;
      FC = 1.21, LINA), LPL (FC = 1.50, SUNA; FC = 1.20, LINA), PPARG (FC = 1.36, SUNA;
      FC = 1.12, LINA), SCD (FC = 1.41, SUNA; FC = 1.17, LINA) and SREBF1 (FC = 1.56,
      SUNA; FC = 1.18, LINA) expression] tissue. Interestingly, gene/gene product
      associations were comparatively low in hepatic and omental adipose tissue
      compared with longissimus muscle, perirenal adipose and subcutaneous adipose
      tissue, indicating matches only in regard to minor concentrations of SCD product
      18:1c9, FADS1 product 20:4n-6 and FADS2 product 18:3n-6 in hepatic tissue, and
      higher concentrations of ACACA and FASN gene products 12:0 and 14:0 and SCD
      product 18:2c9,t11 in omental adipose tissue. Whereas all analyzed tissues
      accumulated dietary PUFA and their ruminally generated biohydrogenation products,
      tissue-divergent preferences for certain fatty acids were identified. This
      descriptive study reports tissue-divergent effects of dietary PUFA and outlines
      the significance of a PUFA intervention with regard to dairy cows' nutritional
      management.

PMID- 23129258
TI  - Evaluation of AMCase and CHIT-1 expression in monocyte macrophages lineage.
AB  - Acidic mammalian chitinase (AMCase) and chitotriosidase (CHIT-1) are two active
      chitinases expressed in humans. The chitinase activity of AMCase was found to be
      causative in allergic inflammation and its expression was found to be induced by
      interleukin-13. CHIT1-1 is expressed by phagocytic cells and extremely high
      levels are seen in lysosomal storage diseases. Despite that AMCase expression in
      the inflammation is under investigation, little is known regarding its regulation
      during macrophages' full maturation and polarization. In this study, we compared
      AMCase and CHIT-1 modulation during monocyte to macrophage transition and
      polarization. Gene expression analysis was investigated by real-time PCR from
      mRNA of human monocytes obtained from buffy coat of healthy volunteers, from mRNA
      of polarized to classically activated macrophages (or M1), obtained by interferon
      (IFN)-gamma and lipopolysaccharide (LPS) treatment, and from mRNA of
      alternatively activated macrophages (or M2) obtained by interleukin (IL)-4
      exposure. Our results showed that the expression of AMCase and CHIT-1 were
      differently modulated in HMMs at different stage of maturation. The behavior of
      these two active chitinase suggests that in the immune response their role is
      complementary.

PMID- 23129260
TI  - Drug-induced generalized skin eruption in a diabetes mellitus patient receiving a
      dipeptidyl peptidase-4 inhibitor plus metformin.
AB  - A generalized skin eruption with strong itching was induced by sitagliptin, a
      dipeptidyl peptidase-4 (DPP-4) inhibitor, in a patient almost 6 months after
      initiation of the drug. Physical examination revealed a spread of skin rash from
      chest to back, and abdomen and thigh. Discontinuation of the drug eliminated the
      skin rash immediately. The emergence of new rash ended, and the rash itself
      withered after 1 week. The spread of the rash gradually shrank and the skin
      lesions subsided, leaving pigmentation 1 month later. Two months after cessation
      of sitagliptin, the skin eruption had subsided and oral steroid medication was
      stopped, but some small eczematous eruptions continued to appear intermittently.
      Although a drug-induced lymphocyte stimulation test was negative for sitagliptin,
      nonspecific radioimmunosorbent test for immunoglobulin E was increased to 532
      IU/mL, with a percentage of eosinophil of 7.4%. Sitagliptin has a phenyl ring,
      carbonyl group, and an absorption spectrum showing three absorption peaks (199.9,
      265.0, 400.1 nm), and its photosensitive mechanism could have been responsible
      for the itchy edematous plaque. In the present case, the initial generalized skin
      eruption may have been induced by an allergic reaction to sitagliptin. Close
      attention should be paid to patients receiving this drug with a history of
      urticaria, and to the development of photosensitivity.

PMID- 23129259
TI  - S100A10 is required for the organization of actin stress fibers and promotion of
      cell spreading.
AB  - Dynamic remodeling of the actin cytoskeleton is crucial for biological processes
      such as cell migration and cell spreading. S100A10 is a member of the S100
      protein family and is involved in intracellular trafficking and cell migration.
      In this study, we examined the role of S100A10 in actin cytoskeletal organization
      and cell spreading. Depletion of S100A10 induced disruption of stress fiber
      formation and delay in cell spreading. Rac1 activation during spreading was
      suppressed by S100A10 knockdown, and exogenous expression of active Rac1 restored
      the ability of cells to spread in the absence of S100A10. Our results demonstrate
      the crucial role of S100A10 in actin dynamics promoting cell spreading via Rac1
      activation.

PMID- 23129257
TI  - Sulforaphane regulates self-renewal of pancreatic cancer stem cells through the
      modulation of Sonic hedgehog-GLI pathway.
AB  - Sulforaphane (SFN), a component of dietary cruciferous vegetables has been
      characterized for its anti-proliferative properties. We have recently
      demonstrated that pancreatic CSCs display activation of sonic hedgehog pathway
      which are fundamental drivers of stem cell renewal, and SFN inhibits the self
      renewal of pancreatic CSCs in vitro. Consistent with these observations, we
      sought to determine the chemopreventive potential of SFN in an in vivo setting.
      We show here for the first time that sulforaphane treatment resulted in a
      significant reduction in the tumor growth of orthotopically implanted primary
      pancreatic CSCs isolated from human pancreatic tumors into the pancreas of
      NOD/SCID/IL2Rgamma mice, which is mediated through the modulation of Sonic
      hedgehog-GLI signaling. Hedgehog pathway blockade by SFN at a dose of 20 mg/kg
      resulted in a 45 % reduction in growth of pancreatic cancer tumors and reduced
      expression of Shh pathway components, Smo, Gli 1, and Gli 2 in mouse tissues.
      Further, SFN inhibited the expression of pluripotency maintaining transcription
      factors Nanog and Oct-4 and angiogenic markers VEGF and PDGFRalpha which are
      downstream targets of Gli transcription. Furthermore, SFN treatment resulted in a
      significant reduction in EMT markers Zeb-1, which correlated with increase in E
      Cadherin expression suggesting the blockade of signaling involved in early
      metastasis. Interestingly, SFN downregulated the expression of Bcl-2 and XIAP to
      induce apoptosis. These data demonstrate that, at a tolerable dose, inhibition of
      Shh pathway by SFN results in marked reduction in EMT, metastatic, angiogenic
      markers with significant inhibition in tumor growth in mice. Since aberrant Shh
      signaling occurs in pancreatic tumorigenesis, therapeutics that target Shh
      pathway may improve the outcomes of patients with pancreatic cancer by targeting
      CSCs, thus suggesting the use of sulforaphane to further improve preventive and
      therapeutic approaches in patients with this devastating disease.

PMID- 23129261
TI  - Protein kinase A phosphorylates NCoR to enhance its nuclear translocation and
      repressive function in human prostate cancer cells.
AB  - Protein kinase A (PKA) phosphorylates diverse protein substrates to modulate
      their function. In this study, we found that PKA specifically phosphorylates the
      RD1 (repression domain 1) domain of nuclear receptor corepressor (NCoR). We
      demonstrated that the Serine-70 of NCoR is identified the critical amino acid for
      PKA-dependent NCoR phosphorylation. Importantly, we found that PKA-dependent
      phosphorylation enhances the nuclear translocation of NCoR. More importantly, the
      activation of PKA enhanced the repressive activity of NCoR in a reporter assay
      and potentiated the antagonist activity in the androgen receptor (AR)-mediated
      transcription. Taken together, these results uncover a regulatory mechanism by
      which PKA positively modulates NCoR function in transcriptional regulation in
      prostate cancer.

PMID- 23129262
TI  - WAP four-disulfide core domain protein 2 mediates the proliferation of human
      ovarian cancer cells through the regulation of growth- and apoptosis-associated
      genes.
AB  - The WAP four-disulfide core domain protein 2 (WFDC2) is frequently overexpressed
      in epithelial ovarian cancer cells and has been proposed as a potential
      biomarker. The biological function of WFDC2 in tumor progression remains unclear.
      In this study, the stable expression of short hairpin RNA (shRNA) against WFDC2
      in the human ovarian SKOV3 cell line was established. Cell proliferation in vitro
      was determined by MTT assay. Cell cycle and apoptosis were analyzed by FACS. The
      expression of genes related to cell proliferation and survival was detected by
      real-time RT-PCR and western blotting. In vivo tumor growth assay was performed
      by establishing WFDC2-knockdown xenografts in nude mice and monitoring tumor
      growth. The expression of WFDC2, Ki67 and activated caspase-3 was analyzed by
      immunohistochemistry in order to determine the role of WFDC2 in proliferation and
      apoptosis. Our results revealed that the silencing of WFDC2 abolished ovarian
      cancer cell proliferation, suppressing tumor formation and growth in ovarian
      cancer cells both in vitro and in vivo. The knockdown of WFDC2 induced
      upregulation of Fasl and the downregulation of cyclin D1 activated caspase-3 and
      Ki67. These results indicate that WFDC2 plays a crucial role in tumor formation
      and growth in ovarian cancer cells. WFDC2 may be a potential therapeutic target
      for epithelial ovarian cancer.

PMID- 23129263
TI  - Investigation of the human bridging veins structure using optical microscopy.
AB  - In this paper, we investigated the brain-sinus junction and especially the
      bridging veins linking these two organs. Two types of optical microscopy were
      used: conventional optical microscopy and digital microscopy. We used thin
      histological sections prepared from a human brain, and stained with Masson's
      trichrome, hemalun and orcein. Finally we observed the path of the bridging vein
      inside the brain-skull interface. At smaller scales, wavy collagen fiber bundles
      were found and characterized inside the vein walls. Taking into account the
      orientations of the different sections with reference to frontal planes, we found
      that the bridging vein has a very complex geometry, which increases the
      difficulty to determine fiber orientations in its walls. Nevertheless, we found
      that collagen fiber bundles are mainly circumferentially oriented in the superior
      sagittal sinus walls. In this paper, we were able to characterize precisely the
      path of the bridging vein from the brain to the sinus, with different
      magnifications.

PMID- 23129265
TI  - Ultrasound imaging of the infraorbital foramen and simulation of the ultrasound
      guided infraorbital nerve block using a skull model.
AB  - PURPOSE: Infraorbital nerve block is used for intraoperative and postoperative
      analgesia in nasal and oral surgery procedures, as well as in the chronic pain
      settings. Ultrasound guidance has not been described in the literature. The aim
      of the study was to assess the quality of ultrasound imaging of the infraorbital
      foramen and develop an "in-plane" technique of the block using a skull model.
      METHODS: The infraorbital foramina were assessed on five skull models immersed in
      the water bath. Ultrasound-guided simulation of an in-plane infraorbital nerve
      block was then performed. Slightly curved needle was placed close to the foramina
      and its visibility was recorded. Success rate and time to locate infraorbital
      foramina, success rate and time to insert the needle close to the foramina under
      ultrasound and correlation between the ultrasound and caliper measurements were
      evaluated and recorded. Data for the left and right foramen were compared.
      RESULTS: The infraorbital foramina were successfully located using ultrasound in
      all 20 cases. Simulation of infraorbital nerve block was also successful in all
      measurements. The time difference between locating or simulating blockade of the
      left and right infraorbital foramina was not statistically significant.
      Correlation between ultrasound measurement and direct measurement using a caliper
      was satisfactory for the distances between the inferior orbital rim and the
      inferior margin of the infraorbital foramen but poor for the distances between
      the lower rim of the orbit and the superior margin of the foramen. CONCLUSIONS:
      This experimental study suggests that the infraorbital foramen is easily located
      using ultrasound and an "in-plane" ultrasound-guided technique for infraorbital
      nerve blockade is feasible on the model.

PMID- 23129264
TI  - Variation of the origin of the left common carotid artery diagnosed by CT
      angiography.
AB  - INTRODUCTION: The left common carotid artery (LCCA) is usually a second branch of
      the aortic arch that arises between the brachiocephalic trunk (BCT) and left
      subclavian artery; relatively frequently, it also arises from or shares a common
      origin with the BCT. In patients with LCCA of anomalous origin, transfemoral
      catheterization into the LCCA is sometimes difficult, and transbrachial or
      transradial approach may be recommended. We evaluated the prevalence of these
      variations on computed tomography (CT) angiography. METHODS: We retrospectively
      reviewed CT angiographic images of 2,357 patients obtained using either of two 64
      slice multidetector CT scanners. All patients were Japanese and underwent
      scanning from the aortic arch to the intracranial region; most had or were
      suspected of having cerebrovascular diseases. RESULTS: We evaluated CT
      angiographic images of 2,352 patients after excluding four patients with LCCA
      occluded at its origin. The LCCA arose from the BCT in 141 patients (6.0 %) and
      had a common origin with the BCT in 130 patients (5.5 %). We found 11 aberrant
      right subclavian artery (0.47 %), and four of the 11 patients (36 %) had LCCA of
      common origin with the right common carotid artery, forming a bicarotid trunk
      (prevalence: 0.17 %). CONCLUSIONS: The total prevalence of variations of LCCA
      origin diagnosed by CT angiography was 11.7 %.

PMID- 23129266
TI  - An anatomic study of the inferior oblique nerve with high-resolution magnetic
      resonance imaging.
AB  - OBJECTIVE: To investigate anatomic features of the inferior oblique nerve (IObN)
      by high-resolution magnetic resonance (MR) imaging and cadaveric dissection.
      METHODS: This study enrolled 100 consecutive outpatients, who underwent 3.0 T MR
      imaging equipped by the 32-channel head coil. The T2-weighted imaging data of
      IObN were extracted for analysis and compared with the findings of microsurgical
      dissection in 14 orbits. RESULTS: 50 male and 50 female subjects allotted to the
      imaging study were aged from 11 to 78 years. In 94 % sides, the IObN was found to
      separate from the inferior rectus muscle (IRM) at the level just behind to the
      posterior pole of the bulb. At the midpoint of the IObN part coursing along the
      orbital floor and above or adjacent to the infraorbital nerve and artery complex,
      the mean distance from the lateral margin of the IRM was 1.0 mm on the right and
      0.9 mm on the left. The IObN showed upward direction change just below the belly
      of the inferior oblique muscle and innervated to it at the equator level in 78
      sides on the right and 89 on the left. Dissected specimens revealed the
      consistent morphological findings of the IObN. CONCLUSIONS: The IObN seems to be
      a relatively consistent structure. Anatomic information on the IObN and
      surrounding structures that are provided by high-resolution MR imaging can be a
      help for safe surgery.

PMID- 23129267
TI  - Intrinsic connectivity between the hippocampus, nucleus accumbens, and ventral
      tegmental area in humans.
AB  - Recent studies suggest that memory formation in the hippocampus is modulated by
      the motivational significance of events, allowing past experience to adaptively
      guide behavior. The effects of motivation on memory are thought to depend on
      interactions between the hippocampus, the ventral tegmental area (VTA), and the
      nucleus accumbens (NAcc). Indeed, animal studies reveal anatomical pathways for
      circuit-level interaction between these regions. However, a homologue circuit
      connectivity in humans remains to be shown. We characterized this circuitry in
      humans by exploiting spontaneous low-frequency modulations in the fMRI signal
      (termed resting-state functional connectivity), which are thought to reflect
      functionally related regions and their organization into functional networks in
      the brain. We examined connectivity in this network across two datasets (hi
      resolution, n = 100; standard resolution, n = 894). Results reveal convergent
      connectivity between the hippocampus, and both the NAcc and the VTA centered on
      ventral regions in the body of the hippocampus. Additionally, we found individual
      differences in the strength of connectivity within this network. Together, these
      results provide a novel task-independent characterization of circuitry underlying
      interactions between the hippocampus, NAcc, and VTA and provide a framework with
      which to understand how connectivity might reflect and constrain the effects of
      motivation on memory.

PMID- 23129268
TI  - Protective effect of cyanidin-3-O-beta-D-glucopyranoside fraction from mulberry
      fruit pigment against oxidative damage in streptozotocin-induced diabetic rat
      bladder.
AB  - AIMS: To determine whether cyanidin-3-O-beta-D-glucopyranoside (C3G) fraction
      from mulberry fruit pigment has protective effects against bladder dysfunction on
      streptozotocin-induced diabetic rats METHODS: Sprague-Dawley rats were divided
      into three groups (n = 12 in each): normal, diabetes (DM), and DM treated with
      C3G fraction (DM + C3G). The DM and DM + C3G groups received a single injection
      of streptozotocin (50 mg/kg) intraperitoneally. Four weeks after the induction of
      diabetes, the DM + C3G group was treated with daily oral C3G (10 mg/kg) dissolved
      in water, for 8 weeks. After 12 weeks of streptozotocin injections, rats in each
      group underwent cystometrography and bladders were used for evaluation of
      apoptosis and oxidative stress. RESULTS: The DM group showed a markedly lower
      maximal intravesical pressure than that observed in the control group, whereas
      rats in the DM + C3G group showed improved maximum intravesical pressure
      associated with minimization of apoptosis, and increased levels of Akt and Bad
      phosphorylation, implying inhibition of pro-apoptotic stimuli. The level of 8
      hydroxy-2-deoxyguanosine, a marker of oxidative stress, was significantly greater
      in the DM group compared to the control group and it was significantly reduced in
      the C3G treated group. Immunoblotting revealed a significant decrease in the
      levels of the superoxide dismutase protein and nerve growth factor in the DM
      group compared with the control group; however, these proteins were upregulated
      in the DM + C3G group compared with the DM group. CONCLUSIONS: The study is the
      first to suggest that C3G fraction have a potency to protect the bladder under
      conditions of diabetes-induced oxidative stress.

PMID- 23129270
TI  - Retraction note: Acamprosate and its efficacy in treating alcohol dependent
      adolescents.

PMID- 23129269
TI  - Fe65 matters: new light on an old molecule.
AB  - The discovery that the main constituents of amyloid deposits, characteristic of
      Alzheimer neuropathology, derive from the proteolytic processing of the membrane
      precursor amyloid precursor protein (APP) is one of the milestones of the
      research history of this disease. Despite years of intense studies, the functions
      of APP and of its amyloidogenic processing are still under debate. One focus of
      these studies was the complex network of protein-protein interactions centered at
      the cytosolic domain of APP, which suggests the involvement of APP in a lively
      signaling pathway. Fe65 was the first protein to be demonstrated to interact with
      the APP cytodomain. Starting from this observation, a large body of data has been
      gathered, indicating that Fe65 is an adaptor protein, which binds numerous
      proteins, further than APP. Among these proteins, the crosstalk with Mena, mDab,
      and Abl suggested the involvement of the Fe65-APP complex in the regulation of
      cell motility, with a relevant role in differentiation and development. Other
      partners, like the histone acetyltransferase Tip60, indicated the possibility
      that the nuclear fraction of Fe65 could be involved in gene regulation and/or DNA
      repair.

PMID- 23129271
TI  - European child and adolescent psychiatry-endorse the importance of prospective
      longitudinal study designs.

PMID- 23129272
TI  - Photo- and thermoresponsive polymersomes for triggered release.
AB  - Microfluidics: Thermo- and photoresponsive polymersomes are assembled using
      capillary microfluidic devices. Encapsulants can be selectively released from the
      thermoresponsive polymersomes if they are incubated at and above temperatures of
      40  degrees C, whereas the photoresponsive polymersomes selectively release
      encapsulants if illuminated with laser light (see picture; NP = nanoparticle).

PMID- 23129273
TI  - Decreased entry of calcium into motor nerve endings upon activation of
      presynaptic cholinergic receptors.

PMID- 23129274
TI  - Synthesis of dopamine in non-dopaminergic neurons of the mediobasal hypothalamus
      of adult rats.

PMID- 23129275
TI  - Mechanisms of delayed inotropic response of mouse atria to activation of beta(2)
      adrenoreceptors.

PMID- 23129276
TI  - A similarity criterion for the forest stand growth.

PMID- 23129277
TI  - Selective accumulation of zircons and ilmenites in diverticula of the sea urchin
      Scaphechinus mirabilis (Agazzis, 1863).

PMID- 23129278
TI  - The genetic structure of an isolated population of the common shrew Sorex araneus
      L. (Mammalia) as determined from microsatellite variation.

PMID- 23129279
TI  - Individual age and odontologic characteristics of root vole.

PMID- 23129280
TI  - Viruses in the pelagic zone of the Barents Sea.

PMID- 23129281
TI  - Interrelation of the digestive processes of the northern fulmar Fulmarus
      glacialis and the cestode Tetrabothrius minor (Cestoda: Tetrabothriidae).

PMID- 23129282
TI  - The fauna of crust soils on rocks.

PMID- 23129283
TI  - Polymorphism of the surface sculpture of placoid scales of sharks (Selachomorpha,
      Elasmobranchii).

PMID- 23129284
TI  - Morphofunctional principles determining the changes in the adaptation strategy of
      ginseng (Panax ginseng C.A. Meyer) during its domestication.

PMID- 23129285
TI  - Expression of the CLOCK, BMAL1, and PER1 circadian genes in human oral mucosa
      cells as dependent on CLOCK gene polymorphic variants.

PMID- 23129286
TI  - Peptide fragment 29-40 of amino acid sequence of monocyte chemoattractant protein
      1 (MCP-1) stimulates monocyte migration in vivo and facilitates wound healing.

PMID- 23129287
TI  - Hormonal regulation of the thymic stage of differentiation of invariant NKT
      cells.

PMID- 23129288
TI  - Attachment and mental health symptoms among U.S. Afghanistan and Iraq veterans
      seeking health care services.
AB  - Attachment theory has become a primary framework for understanding adjustment to
      traumas. In a convenience sample of 157 U.S. service members from the Afghanistan
      and Iraq wars seeking health care services at a Veterans Administration (VA)
      hospital, this study examined (a) the impact of attachment characteristics on
      several key mental health symptoms in this new generation of veterans, (b) the
      relative frequencies of prominent attachment styles in the sample, and (c) how
      these higher order orientations related to study outcomes. First, with
      demographic and military background factors in the model, attachment-related
      anxiety and avoidance were each uniquely associated with posttraumatic stress
      symptoms (PTSS), psychiatric distress, and alcohol misuse, betas = .25 to .60.
      Second, latent class analysis highlighted the underrepresentation of avoidant
      veterans of a dismissive type in the sample. Third, of the different possible
      types of attachment insecurities, veterans with a fearful disorganized
      orientation were also shown to be particularly vulnerable to PTSS and other
      problems, even when compared to preoccupied-dependent persons. These findings
      yield further support for the protective benefit of attachment security, while
      also suggesting the importance of both attachment anxiety and avoidance in the
      context of postdeployment adjustment.

PMID- 23129289
TI  - VEGF and bone cell signalling: an essential vessel for communication?
AB  - Vascular endothelial growth factor (VEGF) is an endothelial cell survival factor
      and is required for effective coupling of angiogenesis and osteogenesis. Although
      central to bone homeostasis, repair and the pathobiology that affect these
      processes, the precise mechanisms coupling endothelial cell function within bone
      formation and remodelling remain unclarified. This review will (i) focus on the
      potential directionality of VEGF signalling in adult bone by identifying the
      predominant source of VEGF within the bone microenvironment, (ii) will summarize
      current VEGF receptor expression studies by bone cells and (iii) will provide
      evidence for a role for VEGF signalling during postnatal repair and osteoporosis.
      A means of understanding the directionality of VEGF signalling in adult bone
      would allow us to most effectively target angiogenic pathways in diseases
      characterized by changes in bone remodelling rates and enhance bone repair when
      compromised.

PMID- 23129290
TI  - TCF4 (e2-2; ITF2): a schizophrenia-associated gene with pleiotropic effects on
      human disease.
AB  - Common SNPs in the transcription factor 4 (TCF4; ITF2, E2-2, SEF-2) gene, which
      encodes a basic Helix-Loop-Helix (bHLH) transcription factor, are associated with
      schizophrenia, conferring a small increase in risk. Other common SNPs in the gene
      are associated with the common eye disorder Fuch's corneal dystrophy, while rare,
      mostly de novo inactivating mutations cause Pitt-Hopkins syndrome. In this
      review, we present a systematic bioinformatics and literature review of the
      genomics, biological function and interactome of TCF4 in the context of
      schizophrenia. The TCF4 gene is present in all vertebrates, and although protein
      length varies, there is high conservation of primary sequence, including the DNA
      binding domain. Humans have a unique leucine-rich nuclear export signal. There
      are two main isoforms (A and B), as well as complex splicing generating many
      possible N-terminal amino acid sequences. TCF4 is highly expressed in the brain,
      where plays a role in neurodevelopment, interacting with class II bHLH
      transcription factors Math1, HASH1, and neuroD2. The Ca(2+) sensor protein
      calmodulin interacts with the DNA binding domain of TCF4, inhibiting
      transcriptional activation. It is also the target of microRNAs, including mir137,
      which is implicated in schizophrenia. The schizophrenia-associated SNPs are in
      linkage disequilibrium with common variants within putative DNA regulatory
      elements, suggesting that regulation of expression may underlie association with
      schizophrenia. Combined gene co-expression analyses and curated protein-protein
      interaction data provide a network involving TCF4 and other putative
      schizophrenia susceptibility genes. These findings suggest new opportunities for
      understanding the molecular basis of schizophrenia and other mental disorders.

PMID- 23129291
TI  - Organic delirious states and other psychiatric disorders: lessons for the
      hepatologists.
AB  - Hepatic encephalopathy (HE) is characterized by a wide variety of
      neuropsychiatric symptoms, and from a psychiatric perspective its nosological
      status calls for clarification. According to the ICD-10 classification, it can be
      classified as delirium due to overt HE's core symptom of clouding of
      consciousness in increasing degrees. Minimal/covert HE with impairment of
      neurocognitive function is more difficult to classify and could correspond to
      Mild Cognitive Impairment or mild degrees of dementia. However, the advantages of
      current psychiatric nosology is the possibility of thorough characterization of
      both dispositional and premorbid psychopathology as well as psychiatric morbidity
      induced by liverdiseases or even treatment. A future closer collaboration between
      hepatologists and psychiatrists is advocated.

PMID- 23129292
TI  - Neurological complications post-liver transplantation: impact of nutritional
      status.
AB  - Nutritional status is significantly altered in patients with end-stage liver
      disease (cirrhosis). Malnutrition is a common complication of cirrhosis and is
      known to be associated with a greater risk of post-operative complications and
      mortality, especially following liver transplantation. Neurological complications
      occur frequently after transplant and the nature and extent of these
      complications may relate to nutritional deficits such as protein-calorie
      malnutrition as well as vitamin and micronutrient deficiencies. A consensus
      document from the International Society on Hepatic Encephalopathy and Nitrogen
      metabolism (ISHEN) has been established in order to address these concerns.
      Careful assessment of nutritional status followed by prompt treatment of
      nutritional deficits has the potential to impact on transplant outcome and, in
      particular, on post-transplant neurological disorders in patients with cirrhosis.

PMID- 23129293
TI  - Disturbance of serotonergic neurotransmission in patients with postmyocardial
      infarction and depression.
AB  - The objective of this study was to assess the hypothesis that patients who
      develop depression after myocardial infarction (MI) have a lower level of brain
      serotonergic neurotransmission through measurement of plasma free fraction of L
      tryptophan and intensity-dependence auditory-evoked potentials (IDAEPs). A cross
      sectional study was carried out in 74 adults after MI. Thirty-four patients
      suffered from depression and 40 patients did not demonstrate depressive symptoms.
      We measured the free fraction, bound and total plasma L-tryptophan, and neutral
      amino acids as well as recording IDAEPs. Patients who developed depression after
      MI showed a significantly lower level in the free fraction of L-tryptophan and in
      the ratios of free fraction of L-tryptophan/total L-tryptophan and free fraction
      of L-tryptophan/neutral amino acids. It is noteworthy that the slope of the
      amplitude/stimulus intensity functions (ASF slope) of the N1/P2 component was
      significantly higher post-MI in depressed patients. Higher ASF slope of the N1/P2
      component associated with a low free fraction of L-tryptophan in plasma reflect a
      low brain serotonergic neurotransmission. These findings suggest an important
      deterioration of brain serotonergic activity as a pathophysiological mechanism in
      post-MI patients for the development of clinical depression. Therefore, we
      propose these biochemical and electrophysiological procedures as noninvasive
      clinical indicators of brain serotonergic activity in these patients.

PMID- 23129295
TI  - LOGICOIL--multi-state prediction of coiled-coil oligomeric state.
AB  - MOTIVATION: The coiled coil is a ubiquitous alpha-helical protein-structure
      domain that directs and facilitates protein-protein interactions in a wide
      variety of biological processes. At the protein-sequence level, the coiled coil
      is readily recognized via a conspicuous heptad repeat of hydrophobic and polar
      residues. However, structurally coiled coils are more complicated, existing in a
      wide range of oligomer states and topologies. As a consequence, predicting these
      various states from sequence remains an unmet challenge. RESULTS: This work
      introduces LOGICOIL, the first algorithm to address the problem of predicting
      multiple coiled-coil oligomeric states from protein-sequence information alone.
      By covering >90% of the known coiled-coil structures, LOGICOIL is a net
      improvement compared with other existing methods, which achieve a predictive
      coverage of ~31% of this population. This leap in predictive power offers better
      opportunities for genome-scale analysis, and analyses of coiled-coil containing
      protein assemblies. AVAILABILITY: LOGICOIL is available via a web-interface at
      http://coiledcoils.chm.bris.ac.uk/LOGICOIL. Source code, training sets and
      supporting information can be downloaded from the same site.

PMID- 23129294
TI  - Identifying clinical symptoms for improving the symptomatic diagnosis of chronic
      rhinosinusitis.
AB  - BACKGROUND: Current symptom criteria for identifying patients with chronic
      rhinosinusitis (CRS) has poor specificity. The objective of this study was to
      test the hypothesis that symptoms drawn from the Task Force on Rhinosinusitis
      (RSTF) criteria and the International Headache Society (IHS) criteria for primary
      headaches can differentiate CRS patients from those with CRS-symptoms but no
      evidence for inflammation (non-CRS). METHODS: A retrospective cohort study from a
      total of 140 charts of patients who received a diagnostic computed tomography
      (CT) scan for CRS symptoms in a tertiary care clinic. The study was conducted in
      2 phases: (1) using a retrospective review of otolaryngologist-documented
      symptoms (ODS) in the medical record; and (2) using patient-reported symptoms
      (PRS) on a prospectively collected customized review of systems form from a
      separate cohort. A radiographic gold standard differentiated CRS from non-CRS
      patients. RESULTS: Subjects in the CRS and non-CRS group were matched for age and
      race and almost universally met symptomatic criteria as defined by the RSTF in
      both study phases. In both study phases, facial pain, but not facial pressure,
      was negatively predictive for CRS (p < 0.05). Similarly, hyposmia was positively
      predictive, whereas facial pain of a pulsating quality and photophobia were
      negatively predictive (p < 0.05), although analysis of PRS was significant only
      when symptom frequency was considered. Nonetheless, significant overlap exists
      between the prevalence and frequency of symptoms in both groups. CONCLUSION: The
      symptom-based diagnosis of CRS is challenging but symptoms of hyposmia is
      positively predictive while facial pain, a throbbing quality, headaches and
      photophobia are negatively predictive and show promise for improving the
      specificity of CRS diagnosis. Further validation studies are needed.

PMID- 23129296
TI  - PBSIM: PacBio reads simulator--toward accurate genome assembly.
AB  - MOTIVATION: PacBio sequencers produce two types of characteristic reads
      (continuous long reads: long and high error rate and circular consensus
      sequencing: short and low error rate), both of which could be useful for de novo
      assembly of genomes. Currently, there is no available simulator that targets the
      specific generation of PacBio libraries. RESULTS: Our analysis of 13 PacBio
      datasets showed characteristic features of PacBio reads (e.g. the read length of
      PacBio reads follows a log-normal distribution). We have developed a read
      simulator, PBSIM, that captures these features using either a model-based or
      sampling-based method. Using PBSIM, we conducted several hybrid error correction
      and assembly tests for PacBio reads, suggesting that a continuous long reads
      coverage depth of at least 15 in combination with a circular consensus sequencing
      coverage depth of at least 30 achieved extensive assembly results. AVAILABILITY:
      PBSIM is freely available from the web under the GNU GPL v2 license
      (http://code.google.com/p/pbsim/).

PMID- 23129297
TI  - DvD: An R/Cytoscape pipeline for drug repurposing using public repositories of
      gene expression data.
AB  - SUMMARY: Drug versus Disease (DvD) provides a pipeline, available through R or
      Cytoscape, for the comparison of drug and disease gene expression profiles from
      public microarray repositories. Negatively correlated profiles can be used to
      generate hypotheses of drug-repurposing, whereas positively correlated profiles
      may be used to infer side effects of drugs. DvD allows users to compare drug and
      disease signatures with dynamic access to databases Array Express, Gene
      Expression Omnibus and data from the Connectivity Map. AVAILABILITY AND
      IMPLEMENTATION: R package (submitted to Bioconductor) under GPL 3 and Cytoscape
      plug-in freely available for download at www.ebi.ac.uk/saezrodriguez/DVD/.

PMID- 23129298
TI  - Binary Interval Search: a scalable algorithm for counting interval intersections.
AB  - MOTIVATION: The comparison of diverse genomic datasets is fundamental to
      understand genome biology. Researchers must explore many large datasets of genome
      intervals (e.g. genes, sequence alignments) to place their experimental results
      in a broader context and to make new discoveries. Relationships between genomic
      datasets are typically measured by identifying intervals that intersect, that is,
      they overlap and thus share a common genome interval. Given the continued
      advances in DNA sequencing technologies, efficient methods for measuring
      statistically significant relationships between many sets of genomic features are
      crucial for future discovery. RESULTS: We introduce the Binary Interval Search
      (BITS) algorithm, a novel and scalable approach to interval set intersection. We
      demonstrate that BITS outperforms existing methods at counting interval
      intersections. Moreover, we show that BITS is intrinsically suited to parallel
      computing architectures, such as graphics processing units by illustrating its
      utility for efficient Monte Carlo simulations measuring the significance of
      relationships between sets of genomic intervals. AVAILABILITY:
      https://github.com/arq5x/bits.

PMID- 23129299
TI  - Pathway hunting by random survival forests.
AB  - MOTIVATION: Pathway or gene set analysis has been widely applied to genomic data.
      Many current pathway testing methods use univariate test statistics calculated
      from individual genomic markers, which ignores the correlations and interactions
      between candidate markers. Random forests-based pathway analysis is a promising
      approach for incorporating complex correlation and interaction patterns, but one
      limitation of previous approaches is that pathways have been considered
      separately, thus pathway cross-talk information was not considered. RESULTS: In
      this article, we develop a new pathway hunting algorithm for survival outcomes
      using random survival forests, which prioritize important pathways by accounting
      for gene correlation and genomic interactions. We show that the proposed method
      performs favourably compared with five popular pathway testing methods using both
      synthetic and real data. We find that the proposed methodology provides an
      efficient and powerful pathway modelling framework for high-dimensional genomic
      data. AVAILABILITY: The R code for the analysis used in this article is available
      upon request.

PMID- 23129300
TI  - MetaGeneTack: ab initio detection of frameshifts in metagenomic sequences.
AB  - SUMMARY: Frameshift (FS) prediction is important for analysis and biological
      interpretation of metagenomic sequences. Since a genomic context of a short
      metagenomic sequence is rarely known, there is not enough data available to
      estimate parameters of species-specific statistical models of protein-coding and
      non-coding regions. The challenge of ab initio FS detection is, therefore, two
      fold: (i) to find a way to infer necessary model parameters and (ii) to identify
      positions of frameshifts (if any). Here we describe a new tool, MetaGeneTack,
      which uses a heuristic method to estimate parameters of sequence models used in
      the FS detection algorithm. It is shown on multiple test sets that the
      MetaGeneTack FS detection performance is comparable or better than the one of
      earlier developed program FragGeneScan. AVAILABILITY AND IMPLEMENTATION:
      MetaGeneTack is available as a web server at
      http://exon.gatech.edu/GeneTack/cgi/metagenetack.cgi. Academic users can download
      a standalone version of the program from
      http://exon.gatech.edu/license_download.cgi.

PMID- 23129301
TI  - HD-CNV: hotspot detector for copy number variants.
AB  - SUMMARY: Copy number variants (CNVs) are a major source of genetic variation.
      Comparing CNVs between samples is important in elucidating their potential
      effects in a wide variety of biological contexts. HD-CNV (hotspot detector for
      copy number variants) is a tool for downstream analysis of previously identified
      CNV regions from multiple samples, and it detects recurrent regions by finding
      cliques in an interval graph generated from the input. It creates a unique
      graphical representation of the data, as well as summary spreadsheets and UCSC
      (University of California, Santa Cruz) Genome Browser track files. The interval
      graph, when viewed with other software or by automated graph analysis, is useful
      in identifying genomic regions of interest for further study. AVAILABILITY AND
      IMPLEMENTATION: HD-CNV is an open source Java code and is freely available, with
      tutorials and sample data from http://daleylab.org. CONTACT: jcamer7@uwo.ca

PMID- 23129303
TI  - New agents for treating dry eye syndrome.
AB  - Dry eye syndrome (DES) is characterized by an inadequate volume and/or quality of
      tears resulting in chronic ocular surface irritation and inflammation. Affecting
      up to 30 % of adults, DES has a considerable impact on visual function and
      quality of life. DES may complicate allergic ocular disease and allergy
      medication may exacerbate DES. The pathophysiology of DES involves osmotic,
      mechanical and inflammatory insults to the tear film, epithelium and
      subepithelial nerve plexus. Various immune-related molecular targets have been
      the focus of research aimed at developing new therapeutic agents for treating
      DES. This article provides an overview of established, new and future agents for
      treating DES.

PMID- 23129305
TI  - Adipose tissue displays trophic properties on normal lung cellular components
      without promoting cancer cells growth.
AB  - Surgical removal is the mainstay for early lung cancer treatment and persistent
      air leaks represent one of the most common clinical complications after lung
      surgery. Adipose tissue transplantation has been proposed as a new strategy for
      regenerative therapy after breast cancer surgery; however its efficacy and safety
      of lung tissue healing after lung resections are unknown. The purpose of this
      study was to test the biological activity of adipose tissue to facilitate lung
      tissue healing and evaluate its effect on cancer cells growth, thus providing
      insight for a possible clinical application. Different in vitro cellular models
      were used to prove the potential biologic effect of autologous fat tissue (AFT)
      in repairing injured lung tissue, and in vivo xenograft models were used to
      evaluate tumor promoting potential of AFT on putative residual cancer cells.
      Treatment of both embryonic (WI-38) and adult lung fibroblasts and of normal
      bronchial epithelial cells (HBEC-KT) with AFT samples, harvested from
      subcutaneous tissue layer of 20 patients undergoing pulmonary metastasectomy,
      improved wound healing and cell proliferation indicating a trophic effect on both
      mesenchymal and epithelial cell types. Conversely AFT-conditioned medium was
      unable to stimulate in vitro proliferation of a lung adenocarcinoma reporter
      cellular system (A549). Moreover, co-injection of AFT and A549 cells in nude mice
      did not promote engraftment and progression of A549 cells. These preclinical
      findings provide preliminary evidence on the potential efficacy of AFT to
      accelerate lung tissue repair without undesired tumor promoting effects on
      putative residual cancer cells.

PMID- 23129304
TI  - Helminth infection in populations undergoing epidemiological transition: a friend
      or foe?
AB  - Helminth infections are highly prevalent in developing countries, especially in
      rural areas. With gradual development, there is a transition from living
      conditions that are dominated by infection, poor sanitation, manual labor, and
      traditional diet to a situation where burden of infections is reduced,
      infrastructure is improved, sedentary lifestyle dominates, and processed food
      forms a large proportion of the calorie intake. The combinations of some of the
      changes in lifestyle and environment are expected to result in alteration of the
      landscape of diseases, which will become dominated by non-communicable disorders.
      Here we review how the major helminth infections affect a large proportion of the
      population in the developing world and discuss their impact on the immune system
      and the consequences of this for other infections which are co-endemic in the
      same areas. Furthermore, we address the issue of decreasing helminth infections
      in many parts of the world within the context of increasing inflammatory,
      metabolic, and cardiovascular diseases.

PMID- 23129306
TI  - Burden of overactive bladder symptom on quality of life in stroke patients.
AB  - AIMS: Overactive bladder (OAB) affects the daily life of many stroke victims. In
      contrast to urinary incontinence, little is known about the prevalence and risk
      factors for OAB among stroke patients. Therefore, we conducted a questionnaire
      survey and analyzed the results together with the clinical data and MRI findings.
      METHODS: A total of 500 volunteer patients with chronic-phase stroke were
      enrolled. The overactive bladder symptom score (OABSS), Short Form 8 (SF-8)
      health survey questionnaire, and some key international questionnaires about
      urinary dysfunction were assessed. RESULTS: We diagnosed 141 patients (28%) with
      OAB, among whom 103 (73%) had never been treated for their symptoms. Patients
      with OAB showed lower scores in both the physical and mental components of the SF
      8, which suggested the burden of OAB on the quality of life of stroke patients.
      Advanced age and male gender were closely related to high OABSS. The modified
      Rankin Scale (mRS) was positively correlated with OABSS. Patients with cerebral
      infarction and those with intracerebral hemorrhage showed a similarly high OABSS.
      The severity of deep white-matter hyperintensity on MRI, classified by the 4
      grade Fazekas scoring system, was significantly associated with high OABSS
      irrespective of presence of accompanying infarcts. Patients with cerebral
      infarcts in the region of anterior circulation showed a higher OABSS than those
      with cerebral infarcts in the posterior circulation. CONCLUSIONS: Based on the
      present risk analysis, patient care should be preferentially focused on the
      detection and treatment of OAB to improve the quality of life of stroke patients.

PMID- 23129308
TI  - Enzymatic processing by MMP-2 and MMP-9 of wild-type and mutated mouse beta
      dystroglycan.
AB  - Dystroglycan (DG) is a membrane-associated protein complex formed by two
      noncovalently linked subunits, alpha-DG, a highly glycosylated extracellular
      protein, and beta-DG, a transmembrane protein. The interface between the two DG
      subunits, which is crucial to maintain the integrity of the plasma membrane,
      involves the C-terminal domain of alpha-DG and the N-terminal extracellular
      domain of beta-DG. It is well known that under both, physiological and
      pathological conditions, gelatinases (i.e. MMP-9 and/or MMP-2) can degrade DG,
      disrupting the connection between the extracellular matrix and the cytoskeleton.
      However, the molecular mechanisms and the exact cleavage sites underlying these
      events are still largely unknown. In a previous study, we have characterized the
      enzymatic digestion of the murine beta-DG ectodomain by gelatinases, identifying
      a main cleavage site on the beta-DG ectodomain produced by MMP-9. In this
      article, we have deepened the pattern of the beta-DG ectodomain digestion by MMP
      2 by using a combined approach based on SDS-PAGE, Orbitrap, and HPLC-ESI-IT mass
      spectrometry. Furthermore, we have characterized the kineticparameters of the
      digestion of some beta-DG ectodomain mutants by gelatinases.

PMID- 23129309
TI  - Pentaarylazafullerenes and their triaryldihydro and tetraarylmonohydro
      precursors.

PMID- 23129307
TI  - Systematic and biotechnological aspects of halophilic and halotolerant
      actinomycetes.
AB  - More than 70 species of halotolerant and halophilic actinomycetes belonging to at
      least 24 genera have been validly described. Halophilic actinomycetes are a less
      explored source of actinomycetes for discovery of novel bioactive secondary
      metabolites. Degradation of aliphatic and aromatic organic compounds,
      detoxification of pollutants, production of new enzymes and other metabolites
      such as antibiotics, compatible solutes and polymers are other potential
      industrial applications of halophilic and halotolerant actinomycetes. Especially
      new bioactive secondary metabolites that are derived from only a small fraction
      of the investigated halophilic actinomycetes, mainly from marine habitats, have
      revealed the huge capacity of this physiological group in production of new
      bioactive chemical entities. Combined high metabolic capacities of actinomycetes
      and unique features related to extremophilic nature of the halophilic
      actinomycetes have conferred on them an influential role for future
      biotechnological applications.

PMID- 23129310
TI  - Cytotoxicity of withaferin A in glioblastomas involves induction of an oxidative
      stress-mediated heat shock response while altering Akt/mTOR and MAPK signaling
      pathways.
AB  - Withaferin A (WA), a steroidal lactone derived from the plant Vassobia
      breviflora, has been reported to have anti-proliferative, pro-apoptotic, and anti
      angiogenic properties against cancer growth. In this study, we identified several
      key underlying mechanisms of anticancer action of WA in glioblastoma cells. WA
      was found to inhibit proliferation by inducing a dose-dependent G2/M cell cycle
      arrest and promoting cell death through both intrinsic and extrinsic apoptotic
      pathways. This was accompanied by an inhibitory shift in the Akt/mTOR signaling
      pathway which included diminished expression and/or phosphorylation of Akt, mTOR,
      p70 S6K, and p85 S6K with increased activation of AMPKalpha and the tumor
      suppressor tuberin/TSC2. Alterations in proteins of the MAPK pathway and cell
      surface receptors like EGFR, Her2/ErbB2, and c-Met were also observed. WA induced
      an N-acetyl-L-cysteine-repressible enhancement in cellular oxidative
      potential/stress with subsequent induction of a heat shock stress response
      primarily through HSP70, HSP32, and HSP27 upregulation and HSF1 downregulation.
      Taken together, we suggest that WA may represent a promising chemotherapeutic
      candidate in glioblastoma therapy warranting further translational evaluation.

PMID- 23129311
TI  - A simple route to synthesize mesoporous ZSM-5 templated by ammonium-modified
      chitosan.
AB  - Uniform mesoporous zeolite ZSM-5 crystals have been successfully fabricated
      through a simple hydrothermal synthetic method by utilizing ammonium-modified
      chitosan and tetrapropylammonium hydroxide (TPAOH) as the meso- and microscale
      template, respectively. It was revealed that mesopores with diameters of 5-20 nm
      coexisted with microporous network within mesoporous ZSM-5 crystals. Ammonium
      modified chitosan was demonstrated to serve as a mesoporogen, self-assembling
      with the zeolite precursor through strong static interactions. As expected, the
      prepared mesoporous ZSM-5 exhibited greatly enhanced catalytic activities
      compared with conventional ZSM-5 and Al-MCM-41 in reactions involving bulky
      molecules, such as the Claisen-Schmidt condensation of 2-hydroxyacetophenone with
      benzaldehyde and the esterification reaction of dodecanoic acid and 2
      ethylhexanol.

PMID- 23129313
TI  - The impact of the stromal cell-derived factor-1-3'A and E-selectin S128R
      polymorphisms on breast cancer.
AB  - Breast cancer is prone to metastasis even in early stage disease. Stromal cell
      derived factor-1 (SDF-1) is a chemokine that has been associated with the egress
      of cancer cells from the primary focus and homing to distant sites, while E
      selectin has been implicated in their trans-endothelial migration. This study was
      performed to evaluate the association between SDF-1-3'A and E-selectin S128R-two
      polymorphisms associated with enhanced function-and the risk of breast cancer, as
      well as their influence on breast cancer outcome. A retrospective analysis was
      conducted on 261 patients and 480 healthy controls using PCR-RFLP. The
      frequencies for the wild-type (GG), GA and AA genotypes of SDF-1 were 43.7, 45.2,
      and 11.1 % in patients, and 51.5, 41.3, and 7.3 % in healthy controls,
      respectively, while the SDF-1-3'A allelic frequency was 33.7 % at patients and
      27.9 % at controls. The SDF-1-3'A carrier group of patients and the A allele of
      SDF-1 were overrepresented among the breast cancer cases (p = 0.04 and 0.02,
      respectively). For the E-selectin S128R polymorphism, the frequencies for the
      wild-type (AA), AC and CC genotypes were 58.6, 38.3, and 3.1 % in patients and
      63.8, 31.4, and 3.8 % in controls, respectively, while the C allelic frequency
      was 22.2 % for patients and 19.5 % for controls. The CC genotype was associated
      with poorer survival. Otherwise, no significant association was detected between
      examined genotypes and tumor characteristics. Overall, our findings support that
      the SDF-1-3'A confers increased susceptibility to breast cancer and that the E
      selectin S128R CC genotype may be related to poorer prognosis. Investigation in
      bigger cohorts of patients is warranted.

PMID- 23129314
TI  - Acylated ghrelin protects hippocampal neurons in pilocarpine-induced seizures of
      immature rats by inhibiting cell apoptosis.
AB  - Ghrelin has two major molecular forms, acylated ghrelin (AG) and unacylated
      ghrelin (UAG). Only AG to bind growth hormone secretagogue receptor 1a (GHSR-1a)
      has central endocrine activities. An antiapoptotic effect of AG in cortical
      neuronal cells has recently been reported. However, whether there is a
      neuroprotective effect of AG in hippocampal neurons of pilocarpine-induced
      seizures in rats, is still unknown. Therefore, in the present study, the
      underlying mechanism of AG on lithium-pilocarpine-induced excitotoxicity was
      examined in the hippocampus of rat. The results showed that AG inhibited
      pilocarpine-induced apoptosis. Exposure of rats to the receptor-specific
      antagonist D-Lys-3-GHRH-6 abolished the protective effects of AG against
      epilepsy. Administration of AG resulted in increased expression of phosphor-Akt
      in status epilepticus model in rats, which was accompanied with the attenuation
      of hippocampal cell death. Furthermore, administration of AG resulted in
      decreased expression of phosphor-JNK in pyramidal neurons of hippocampus after
      status epilepsy, which was also accompanied with the attenuation of hippocampal
      cell death, too. In addition, AG increased the Bcl-2/Bax ratio and inhibited
      caspase-3 activation. The data indicate that AG can function as a neuroprotective
      agent that inhibits apoptotic pathways. These effects may be mediated via
      activation of the PI3K/Akt pathway.

PMID- 23129315
TI  - A mechanistic investigation into non-infarcted brain injury induced by cerebral
      artery microemboli.
AB  - To establish a rat brain injury by non-infarction process model induced by
      cerebral artery microemboli which would be used to further explore the neural
      injury mechanisms of cerebral artery microemboli. Seventy-two Sprague-Dawley rats
      were randomly divided into the microemboli group and the sham group; 100 25-50
      MUm microemboli in 300 MUl or the same amount of saline were injected into the
      left carotid artery, respectively. The severity of neuron damage was assessed 3
      and 7 days after the operation, using haematoxylin-eosin (HE) staining and
      immunohistochemical staining for caspase-3. Immunohistochemical staining for
      CD11b and GFAP were used to quantitatively analyse hyperplasia and the activation
      of microglia and astrocytes. TNF-alpha expression was detected by using ELISA and
      the NF-kappaB expression was detected by employing Western blotting. The results
      of HE staining had shown that ischaemic infarct foci were not detected in either
      the microemboli group or sham group. Only a few apoptotic cells and a few cells
      with the positive expression of CD11b and GFAP were detected in the sham group.
      And compared with that of the sham group, the number of apoptotic cells and the
      positive expression of CD11b and GFAP in the microemboli group were significantly
      increased (P < 0.001). These parameters were also significantly increased 7 days
      after the operation compared to rats 3 days after surgery (P < 0.001). The
      expressions of TNF-alpha and NF-kappaB were significantly increased in the
      microemboli group (P < 0.001), and the increase of the expression of TNF-alpha
      and NF-kappaB on the 3 days was more significant compared to that of TNF-alpha
      and NF-kappaB on 7 days (P < 0.001). Injection of 25-50 MUm microemboli at a dose
      of 100 microemboli in 300 MUl into the carotid artery of rats did not result in
      cerebral infarction, but led to neuronal apoptosis, hyperplasia and activation of
      microglia and astrocytes. This leads us to conclude that TNF-alpha and NF-kappaB
      may play important roles in the pathogenesis of neuronal apoptosis induced by
      microemboli in the cerebral arteries.

PMID- 23129312
TI  - Predictions not commands: active inference in the motor system.
AB  - The descending projections from motor cortex share many features with top-down or
      backward connections in visual cortex; for example, corticospinal projections
      originate in infragranular layers, are highly divergent and (along with
      descending cortico-cortical projections) target cells expressing NMDA receptors.
      This is somewhat paradoxical because backward modulatory characteristics would
      not be expected of driving motor command signals. We resolve this apparent
      paradox using a functional characterisation of the motor system based on
      Helmholtz's ideas about perception; namely, that perception is inference on the
      causes of visual sensations. We explain behaviour in terms of inference on the
      causes of proprioceptive sensations. This explanation appeals to active
      inference, in which higher cortical levels send descending proprioceptive
      predictions, rather than motor commands. This process mirrors perceptual
      inference in sensory cortex, where descending connections convey predictions,
      while ascending connections convey prediction errors. The anatomical substrate of
      this recurrent message passing is a hierarchical system consisting of
      functionally asymmetric driving (ascending) and modulatory (descending)
      connections: an arrangement that we show is almost exactly recapitulated in the
      motor system, in terms of its laminar, topographic and physiological
      characteristics. This perspective casts classical motor reflexes as minimising
      prediction errors and may provide a principled explanation for why motor cortex
      is agranular.

PMID- 23129317
TI  - The limbal epithelium of the eye--a review of limbal stem cell biology, disease
      and treatment.
AB  - The limbus is a narrow band of tissue that encircles the cornea, the transparent
      'window' into the eye. The outermost layer of the cornea is the epithelium, which
      is necessary for clear vision. The limbus acts as a 'reservoir' for limbal stem
      cells which maintain and regenerate the corneal epithelium. It also functions as
      a barrier to the conjunctiva and its blood vessels. Limbal stem cell deficiency
      is a general term for diseases which are characterised by the impairment of the
      limbus, limbal stem cells and their ability to replenish the corneal epithelium
      through proliferation and differentiation. Consequently, sufferers experience
      chronic pain and progressive blindness. This paper will highlight the salient
      milestones of limbal stem cell biology and potential future treatments for limbal
      stem cell deficiency.

PMID- 23129316
TI  - Apo A5 -1131T/C, FgB -455G/A, -148C/T, and CETP TaqIB gene polymorphisms and
      coronary artery disease in the Chinese population: a meta-analysis of 15,055
      subjects.
AB  - The Apolipoprotein A5 (APO A5) -1131T/C, fibrinogen beta (FgB) -455G/A, -148C/T,
      and cholesteryl ester transfer protein (CETP) TaqIB gene polymorphisms have been
      indicated to be associated with the coronary artery disease (CAD) risk, but the
      individual study results are still inconsistent. To explore the relationship
      between APO A5 -1131T/C, FgB -455G/A, -148C/T, and CETP TaqIB gene polymorphisms
      and CAD in the Chinese population, the current meta-analysis involving 15,055
      subjects from 40 individual studies was conducted. The pooled odds ratio (OR) for
      the association between APO A5 -1131T/C, FgB -455G/A, -148C/T, and CETP TaqIB
      gene polymorphisms and CAD and its corresponding 95 % confidence interval (95 %
      CI) were evaluated by random or fixed effect model. A significant association
      between APO A5 -1131T/C gene polymorphism and CAD in the Chinese population was
      found under an allelic (OR: 1.33, 95 % CI: 1.22-1.44, P < 0.00001), recessive
      (OR: 1.67, 95 % CI: 1.25-2.25, P = 0.0006), dominant (OR: 0.820, 95 % CI: 0.767
      0.876, P = 1.0 * 10(-10)), homozygous (OR: 2.36, 95 % CI: 1.55-3.58, P < 0.0001)
      and heterozygous genetic models (OR: 1.136, 95 % CI:1.075-1.200, P = 1.0 * 10(
      10)). A significant association between FgB -455G/A gene polymorphism and CAD was
      also detected in the Chinese population under an allelic (OR: 1.50, 95 % CI: 1.25
      1.81, P < 0.0001), dominant (OR: 0.864, 95 % CI: 0.819-0.912, P = 1.0 * 10(-10)),
      homozygous (OR: 1.616, 95 % CI: 1.213-2.152, P = 0.001) and heterozygous genetic
      models (OR: 1.245, 95 % CI:1.138-1.361, P = 1.0 * 10(-10)). No significant
      association was found between them under a recessive genetic model (OR: 1.124, 95
      % CI: 0.844-1.497, P = 0.424). A significant association was also found between
      FgB -148C/T gene polymorphism and CAD in the Chinese population under an allelic
      (OR: 1.34, 95 % CI: 1.06-1.71, P = 0.02), recessive (OR: 1. 65, 95 % CI: 1.02
      2.69, P = 0.04), dominant (OR: 0.924, 95 % CI: 0.872-0.978, P = 0.007) and
      homozygous genetic models (OR: 0.968, 95 % CI: 0.942-0.995, P = 0.018). No
      significant association was found between them under a heterozygous genetic model
      (OR: 0.979, 95 % CI: 0.937-1.023, P = 0.342). In the whole Chinese population, no
      significant association between the CETP TaqIB gene polymorphism and CAD was
      found under an allelic (OR: 1.17, 95 % CI: 0.94-1.45, P = 0.15), dominant (OR:
      1.46, 95 % CI: 0.80-2.67, P = 0.22) or recessive genetic models (OR: 0.68, 95 %
      CI: 0.32-1.44, P = 0.31). However, in the subgroup analysis stratified by
      ethnicity, there was a significant association between them under an allelic (OR:
      1.27, 95 % CI: 1.07-1.52, P = 0.007) and dominant genetic model (OR: 2.04, 95 %
      CI: 1.49-2.79, P < 0.00001) in the Han subgroup. In the Chinese population, the
      APO A5 -1131T/C and FgB -455G/A, -148C/T gene polymorphisms were implied to be
      associated with CAD susceptibility. The APO A5 -1131C, FgB -455A, and -148T
      alleles might confer susceptibility to CAD. CETP TaqIB gene polymorphism was
      suggested to be associated with CAD susceptibility in the Chinese Han population.
      Carriers with B1 allele of CETP TaqIB gene might be predisposed to CAD in the
      Chinese Han population.

PMID- 23129318
TI  - Does maternal smoking during pregnancy associate recurrent wheezing in infants by
      altering neonatal serum folate status?

PMID- 23129319
TI  - Economic incentives and foster child adoption.
AB  - Every year, a large number of children in the United States enter the foster care
      system. Many of them are eventually reunited with their biological parents or
      quickly adopted. A significant number, however, face long-term foster care, and
      some of these children are eventually adopted by their foster parents. The
      decision by foster parents to adopt their foster child carries significant
      economic consequences, including for feiting foster care payments while also
      assuming responsibility for medical, legal, and educational expenses, to name a
      few. Since 1980, U.S. states have begun to offer adoption subsidies to offset
      some of these expenses, significantly lowering the cost of adopting a child who
      is in the foster care system. This article presents empirical evidence of the
      role that these economic incentives play in foster parents' decision of when, or
      if, to adopt their foster child. We find that adoption subsidies increase
      adoptions through two distinct price mechanisms: by lowering the absolute cost of
      adoption, and by lowering the relative cost of adoption versus long-term foster
      care.

PMID- 23129320
TI  - Adherence to ICCS nomenclature guidelines in subsequent literature: a
      bibliometric study.
AB  - AIMS: Since the publication of the 2006 International Children's Continence
      Society (ICCS) guidelines on terminologies for lower urinary tract dysfunction in
      children, little is known of their impact. In this study, we aim to quantify the
      adherence to the guidelines in the published literature, and to examine whether
      Medical Subject Headings (MeSH) in MEDLINE reflect the recommended "new" ICCS
      terminology. METHODS: Seven pairs of pre-specified paired terms (obsolete and
      recommended by the ICCS) were searched, limited to paediatric literature
      published between 2002 and 2010. Their use in the literature was compared between
      the pre-guideline (2002-2005) and post-guideline (2007-2010) period and across
      geographical regions. MeSH in MEDLINE were examined for the use of ICCS preferred
      terminology. RESULTS: Publications in paediatric urinary incontinence have shown
      a 49% increase from 2002-2005 to 2007-2010 (55-82 per year). There was about a
      fourfold increase in the likelihood of usage of ICCS recommended terminologies
      post ICCS guideline publication (OR: 4.19, 95% CI: 3.04-5.78, P < 0.001).
      Approximately 25% of the studies published between 2007 and 2010 used obsolete
      terminologies. Analysis indicated satisfactory uptake for most terms, with the
      exception of "urotherapy." There was no significant geographical variation in
      uptake. More than half of the ICCS-recommended terms (4/7) did not appear in the
      current MeSH indexing tree and scope notes. CONCLUSIONS: Overall uptake of
      recommended terms following release of ICCS terminology guidelines was
      encouraging although it remains suboptimal for certain terms. Efforts need to be
      made to improve the current MEDLINE indexing so that MeSH terms reflect
      terminology recommended by the ICCS.

PMID- 23129321
TI  - Risk of adverse events following oseltamivir treatment in influenza outpatients,
      Vaccine Safety Datalink Project, 2007-2010.
AB  - PURPOSE: An association between the influenza antiviral medication oseltamivir
      and neuropsychiatric events has been suggested by post-marketing case reports in
      Japan. This possible association was not supported by cohort studies in the U.S.
      conducted prior to the 2009 influenza A (H1N1) pandemic, when usage rates were
      comparatively low. We assessed oseltamivir safety before and during the pandemic
      using biologically plausible risk intervals, particularly focusing on psychiatric
      events. METHODS: Outpatients with influenza episodes from January 2007 through
      June 2010 were identified using diagnosis codes and positive tests at eight
      health care systems (sites) in the Vaccine Safety Datalink Project. Oseltamivir
      treated and untreated patients were matched according to calendar week, age, sex,
      site, and propensity for treatment. Within this matched cohort, conditional
      logistic regression models were used to estimate the risk of four
      neuropsychiatric and five other adverse events (AEs) during pre-specified risk
      intervals. RESULTS: Among 27,684 matched pairs, no associations were identified
      between oseltamivir treatment and any pre-defined AE. The absolute risks of
      incident psychiatric events in the 1-7 day risk interval were 0.126% for
      oseltamivir-treated and 0.105% for untreated patients (odds ratio = 1.21, 95%
      confidence interval [CI]: 0.74, 1.97; risk difference = 0.022%, 95% CI: -0.035%,
      0.078%); the most common diagnosis was unspecified anxiety state. Results were
      similar for 1-14 and 1-2 day risk intervals and for pediatric/adolescent
      subgroups. CONCLUSIONS: Consistent with prior U.S. cohort studies, no evidence
      was identified for an increased risk of neuropsychiatric or other AEs following
      oseltamivir treatment. Safety should be prospectively monitored to inform
      antiviral medication usage recommendations.

PMID- 23129322
TI  - Triazole-based one-dimensional spin-crossover coordination polymers.
AB  - One-dimensional coordination Fe(II) polymers constructed through triple N(1),N(2)
      1,2,4-triazole bridges form a unique class of spin-crossover materials, the
      synthetic versatility of which allows tuning the spin-crossover properties, the
      design of gels, films, liquid crystals, and nanoparticles and single-particle
      addressing. This Minireview provides the first complete overview of these very
      attractive switchable materials and their most recent developments.

PMID- 23129323
TI  - Spleen endothelial cells from patients with myelofibrosis harbor the JAK2V617F
      mutation.
AB  - Increased microvessel density contributes to abnormal BM and spleen
      microenvironment in myelofibrosis (MF). Taking advantage of the JAK2V617F
      mutation as a marker of malignancy, in the present study, we investigated whether
      splenic endothelial cells (ECs) obtained from capillaries by laser
      microdissection or from fresh spleen tissue by cell culture or cell sorting
      harbored such mutation in patients bearing the mutation in their granulocytes and
      undergoing splenectomy for therapeutical reasons. To extend the analysis to the
      ECs of large vessels, endothelial tissue from the splenic vein was also studied.
      We found JAK2V617F(+) ECs in 12 of 18 patients also bearing the mutation in their
      granulocytes. In 3 patients, the mutation was found in at least 2 different EC
      samples obtained by laser microdissection, cell culture, or cell sorting. The
      mutation was detected in the splenic vein ECs of 1 of 6 patients investigated. In
      conclusion, we provide evidence that some ECs from the spleen and splenic veins
      of patients with MF bear the JAK2V617F mutation. We suggest that splenic ECs are
      involved in the process of malignant transformation in MF.

PMID- 23129324
TI  - Tracking the bioreduction of disulfide-containing cationic dendrimers.
AB  - Disulfides enhance the transfection efficacy and reduce the toxicity of cationic
      gene delivery polymers. A quantitative analysis is provided of the bioreduction
      of a dynamic bioreducible dendritic polycationic probe in four cell lines. Such
      knowledge is indispensible for understanding and optimizing bioreducible drug and
      gene delivery systems.

PMID- 23129325
TI  - Contrasting effects of type 2 and type 1 diabetes on plasma RBP4 levels: the
      significance of transthyretin.
AB  - Retinol-binding protein 4 (RBP4) is the principle carrier of retinol in the human
      plasma, which circulates as a complex with transthyretin (TTR), a homotetrameric
      thyroxine transport protein. Although this complex formation is thought to
      prevent glomerular filtration of RBP4, it also stabilizes the quaternary
      structure of TTR. Recent studies indicate elevated plasma levels of RBP4 in type
      2 diabetes (T2D). In contrast, reduced RBP4 levels were observed in type 1
      diabetes (T1D). Herein, we critically examine the probable mechanisms involved in
      the regulation of RBP4 and TTR levels during T2D and T1D. The available evidences
      point to the involvement of pancreatic factors in regulating the expression of
      both RBP4 and TTR. It appears that during T1D, TTR levels are reduced and it
      exists predominantly as a monomer that may interfere its interaction with RBP4
      resulting in its loss through glomerular filtration. However, plasma TTR levels
      remain high under T2D conditions and thus reducing glomerular filtration of RBP4.
      Therefore, the plasma TTR levels appear to be an important determinant of plasma
      RBP4 levels in these two diabetic conditions.

PMID- 23129326
TI  - The dopamine dysfunction in schizophrenia revisited: new insights into topography
      and course.
AB  - Schizophrenia has long been associated with an imbalance in dopamine (DA)
      neurotransmission, and brain imaging has played an important role in advancing
      our knowledge and providing evidence for the dopaminergic abnormalities. This
      chapter reviews the evidence for DA dysfunction in different brain regions in
      schizophrenia, in particular striatal, extrastriatal, and prefrontal regions,
      with emphasis on recently published findings. As opposed to the traditional view
      that most striatal dopaminergic excess, associated with the positive symptoms of
      schizophrenia, involves the dopaminergic mesolimbic pathway, recent evidence
      points to the nigrostriatal pathway as the area of highest dysregulation.
      Furthermore, evidence from translational research suggests that dopaminergic
      excess may be present in the prodromal phase, and may by itself, as suggested by
      the phenotype observed in transgenic mice with developmental overexpression of
      dorso-striatal D(2) receptors, be an early pathogenic condition, leading to
      irreversible cortical dysfunction.

PMID- 23129327
TI  - Role of dopamine D(2) receptors for antipsychotic activity.
AB  - This review summarizes the current state of knowledge regarding the proposed
      mechanisms by which antipsychotic agents reduce the symptoms of schizophrenia
      while giving rise to adverse side effects. The first part summarizes the
      contribution of neuroimaging studies to our understanding of the neurochemical
      substrates of schizophrenia, putting emphasis on direct evidence suggestive of a
      presynaptic rather than a postsynaptic dysregulation of dopaminergic
      neurotransmission in this disorder. The second part addresses the role of D(2)
      and non-D(2) receptor blockade in the treatment of schizophrenia and highlights a
      preponderant role of D(2) receptors in the mechanism of antipsychotic action.
      Neuroimaging studies have defined a narrow, but optimal, therapeutic window of 65
      78 % D(2) receptor blockade within which most antipsychotics achieve optimal
      clinical efficacy with minimal side effects. Some antipsychotics though do not
      conform to that therapeutic window, notably clozapine. The reasons for its
      unexcelled clinical efficacy despite subthreshold levels of D(2) blockade are
      unclear and current theories on clozapine's mechanisms of action are discussed,
      including transiency of its D(2) receptor blocking effects or preferential
      blockade of limbic D(2) receptors. Evidence is also highlighted to consider the
      use of extended antipsychotic dosing to achieve transiency of D(2) blockade as a
      way to optimize functional outcomes in patients. We also present some critical
      clinical considerations regarding the mechanisms linking dopamine disturbance to
      the expression of psychosis and its blockade to the progressive resolution of
      psychosis, keeping in perspective the speed and onset of antipsychotic action.
      Finally, we discuss potential novel therapeutic strategies for schizophrenia.

PMID- 23129329
TI  - Serotonergic mechanisms as targets for existing and novel antipsychotics.
AB  - A variety of serotonin (5-HT) receptors, especially 5-HT(2A), 5-HT(1A), 5-HT(6),
      5-HT(7), and 5-HT(2C), have been postulated to contribute to the mechanism of
      action of atypical antipsychotic drugs (APDs), i.e., APDs which cause fewer
      extrapyramidal side effects (EPS) at clinically optimal doses, in contrast with
      typical APDs, which are more likely to cause EPS. This advantage, rarely
      disputed, has made such drugs the preferred treatment for schizophrenia and other
      indications for APDs. These 5-HT receptors are still of interest as components of
      novel multireceptor or stand-alone APDs, and potentially to remediate cognitive
      deficits in schizophrenia. Almost all currently available atypical APDs are 5
      HT(2A) receptor inverse agonists, as well as dopamine (DA) D(2) receptor
      antagonists or partial agonists. Amisulpride, an exceptional atypical APD, has 5
      HT(7) antagonism to complement its DA D(2/3) antagonism. Some atypical APDs are
      also 5-HT(1A) partial agonists, 5-HT(6), or 5-HT(7) antagonists, or some
      combination of the above. 5-HT(2C) antagonism has been found to contribute to the
      metabolic side effects of some atypical APDs, whereas 5-HT(2C) agonists have
      potential as stand-alone APDs and/or cognitive enhancers. This review will
      provide an update of current preclinical and clinical evidence for the role of
      these five 5-HT receptors in the actions of current APDs and for the development
      of novel psychotropic drugs.

PMID- 23129330
TI  - Managing the prodrome of schizophrenia.
AB  - It is a well-known fact that managing schizophrenia patients as early as possible
      has a positive impact on the psychopathological and psychosocial outcomes of the
      disorder. Identifying people at risk for this serious disorder before its
      outbreak has become a major research aim in the past decade. Consequently, the
      intuitive notion that intervening at this early stage, before a diagnosis of
      schizophrenia is established, could be a preventive measure has been
      scientifically studied. In this context, a number of interventions, both
      pharmacological and psychosocial, have been evaluated in prospective controlled
      clinical trials. Amisulpride, olanzapine, risperidone, omega-3 fatty acids, and
      antidepressants have been compared to placebo or other control interventions and
      have been found somewhat helpful. With the exception of omega-3 fatty acids,
      however, the original positive findings were not maintained in follow-up studies.
      In addition, the rates of conversion to psychosis, although generally lower in
      the experimental treatment groups, were also reasonably low in the control
      groups. Similar findings have been established in psychotherapy trials.All
      evidence taken together makes it difficult to justify specific interventions at
      the prodromal stage of schizophrenia from the perspective of preventing or
      delaying the onset of the disorder. On the other hand, as many of the affected
      individuals suffer considerably, symptomatic treatment certainly is called for
      even though the evidence whether it should be pharmacological or psychosocial is
      not yet available.

PMID- 23129331
TI  - Metabolic consequences of antipsychotic therapy: preclinical and clinical
      perspectives on diabetes, diabetic ketoacidosis, and obesity.
AB  - Antipsychotic drugs, particularly second-generation antipsychotics (SGAs), have
      reduced the burden to society of schizophrenia, but many still produce excessive
      weight gain. A significant number of SGAs also act directly to impair glycemic
      control causing insulin resistance, impaired glucose tolerance and type 2
      diabetes, and also rarely diabetic ketoacidosis (DKA). Schizophrenia itself is
      almost certainly causal in many endocrine and metabolic disturbances, making this
      population especially vulnerable to the adverse metabolic consequences of
      treatment with SGAs. Hence, there is an urgent need for a new generation of
      antipsychotic drugs that provide efficacy equal to the best of the SGAs without
      their liability to cause weight gain or type 2 diabetes. In the absence of such
      safe and effective alternatives to the SGAs, there is a substantial clinical need
      for the introduction of new antipsychotics without adverse metabolic effects and
      new antiobesity drugs to combat these metabolic side effects. We discuss the
      adverse metabolic consequences of schizophrenia, its exacerbation by a lack of
      social care, and the additional burden placed on patients by their medication. A
      critical evaluation of the animal models of antipsychotic-induced metabolic
      disturbances is provided with observations on their strengths and limitations.
      Finally, we discuss novel antipsychotic drugs with a lower propensity to increase
      metabolic risk and adjunctive medications to mitigate the adverse metabolic
      actions of the current generation of antipsychotics.

PMID- 23129332
TI  - Medical needs in the treatment of psychotic disorders.
AB  - Schizophrenia and psychotic disorders represent psychiatric disease patterns
      characterized by remarkable impairment arising from alterations in cognition,
      perception, and mood. Although these severe illnesses have been known for more
      than 100 years, psychopharmacological treatment of their characteristically broad
      spectrum of symptoms as well as patients' quality of life, compliance, and time
      to relapse still remain a challenge in everyday clinical practice. In the
      following, we will provide a brief synopsis of first-generation antipsychotics
      (FGAs) followed by a detailed description of current second-generation
      antipsychotics (SGAs) along with their effects and side effects to evaluate unmet
      needs in the treatment of schizophrenia and psychotic disorders.Overall, drug
      profiles differ concerning their efficacy, associated side effects, cost, and
      mechanism of action. Thus, a shared decision-making process taking all these
      factors into account is necessary to develop an effective treatment based on
      currently approved compounds. To date, however, the spectrum of options is
      limited and only serves a limited proportion of patients. In addition, certain
      symptoms do not respond well to currently available strategies or respond only at
      the price of considerable side effects leading to reduced compliance and
      adherence in a substantial number of cases.Unmet needs in the field of
      antipsychotic treatment are found in a wide range of areas starting from
      efficacy, safety and tolerability, compliance and adherence, and continuing to
      stage-dependent and more personalized approaches.

PMID- 23129333
TI  - Antipsychotics in the treatment of bipolar disorder.
AB  - Atypical antipsychotics have an important role in the acute and maintenance
      treatment of bipolar disorder. While robust evidence supports the efficacy of
      these agents in the treatment of mania and in the prevention of manic relapse,
      few atypical antipsychotics have shown efficacy in the treatment or prevention of
      depressive episodes. These agents pose a lower risk of extrapyramidal side
      effects compared to typical neuroleptics, but carry a significant liability for
      weight gain and other metabolic side effects such as hyperglycemia and
      hyperlipidemia. More comparative effectiveness studies are needed to assess the
      optimal treatment regimens, including the relative benefits and risks of
      antipsychotics versus mood stabilizers. The exploration of the molecular
      mechanisms of antipsychotics has helped to shed further light on the underlying
      neurobiology of bipolar disorder, since these compounds target systems thought to
      be key to the pathophysiology of bipolar disorder. In addition to modulating
      monoaminergic neurotransmission, atypical antipsychotics appear to share
      properties with mood-stabilizing agents known to alter intracellular signal
      transduction leading to changes in neuronal activity and gene expression.
      Atypical antipsychotic drugs have been shown to exhibit neuroprotective
      properties that are mediated by upregulation of trophic and cellular resilience
      factors. Building on our understanding of existing therapeutics, especially as it
      relates to underlying disease pathology, newer "plasticity enhancing" strategies
      hold promise for future treatments of bipolar disorder.

PMID- 23129328
TI  - Dopamine receptor signaling and current and future antipsychotic drugs.
AB  - All currently efficacious antipsychotic drugs have as part of their mechanism the
      ability to attenuate some or all of the signaling through the dopamine D(2)
      receptor. More recently, the dopamine D(1) receptor has been hypothesized to be a
      promising target for the treatment of negative and/or cognitive aspects of
      schizophrenia that are not improved by current antipsychotics. Although cAMP has
      been presumed to be the primary messenger for signaling through the dopamine
      receptors, the last decade has unveiled a complexity that has provided exciting
      avenues for the future discovery of antipsychotic drugs (APDs). We review the
      signaling mechanisms of currently approved APDs at dopamine D(2) receptors, and
      note that aripiprazole is a compound that is clearly differentiated from other
      approved drugs. Although aripiprazole has been postulated to cause dopamine
      stabilization due to its partial D(2) agonist properties, a body of literature
      suggests that an alternative mechanism, functional selectivity, is of primary
      importance. Finally, we review the signaling at dopamine D(1) receptors, and the
      idea that drugs that activate D(1) receptors may have use as APDs for improving
      negative and cognitive symptoms. We address the current state of drug discovery
      in the D(1) area and its relationship to novel signaling mechanisms. Our
      conclusion is that although the first APD targeting dopamine receptors was
      discovered more than a half-century ago, recent research advances offer the
      possibility that novel and/or improved drugs will emerge in the next decade.

PMID- 23129334
TI  - The pharmacogenetics of antipsychotic treatment.
AB  - There is substantial interindividual variability in the effects of treatment with
      antipsychotic drugs not only in the emergence of adverse effects but also in
      symptom response. It is becoming increasingly clear that much of this variability
      is due to genetic factors; pharmacogenetics is the study of those factors, with
      the eventual goal of identifying genetic predictors of treatment effects. There
      have been many reported associations of single nucleotide polymorphisms (SNPs) in
      candidate genes with the consequences of antipsychotic drug treatment. Thus
      variations in dopaminergic and serotoninergic genes may influence positive and
      negative symptom outcome, respectively. Among the adverse effects, tardive
      dyskinesia and weight gain have been the most studied, with some consistent
      associations of functional SNPs in genes relating to pharmacological mechanisms.
      Technological advance has permitted large-scale genome-wide association studies
      (GWAS), but as yet there are few reports that replicate prior findings with
      candidate genes. Nevertheless, GWAS may identify associations which provide new
      clues relating to underlying mechanisms.

PMID- 23129335
TI  - Interactions and monitoring of antipsychotic drugs.
AB  - As a consequence of individualized antipsychotic pharmacotherapy, many patients
      need more than a single drug, since they do not respond sufficiently to
      monotherapy. Other patients suffer from comorbid diseases and therefore require
      additional drugs from other pharmacological classes. Drug combinations, however,
      can give rise to pharmacokinetic and/or pharmacodynamic drug-drug interactions.
      Evaluation of pharmacokinetic interactions with antipsychotic drugs must consider
      substrate, inhibitor, and inducer properties for the cytochrome P450 (CYP)
      isoenzymes of all combined drugs. For consideration of pharmacodynamic
      interactions, special attention must be given to effects on dopamine D(2),
      histamine H(1), and acetylcholine M(1) receptors and on cardiac potassium
      channels. Additive pharmacological actions of combined drugs on these target
      structures can induce adverse reactions such as extrapyramidal symptoms,
      drowsiness, metabolic disturbances leading to weight gain and cardiac problems,
      cognitive impairment, delirium, or ventricular arrhythmia. Measuring plasma
      concentrations, i.e., therapeutic drug monitoring (TDM), is valuable to adjust
      antipsychotic medication when drug combinations contain inhibitors or inducers
      that alter plasma concentrations of the antipsychotic drugs. Amalgamating the
      broad knowledge on drug-drug interactions and using appropriately the option to
      monitor plasma concentrations in blood will help to apply complex combination
      therapies with antipsychotic drugs with maximal efficiency and safety.

PMID- 23129336
TI  - Delivery systems and dosing for antipsychotics.
AB  - Schizophrenia is a devastating illness, affecting approximately 1-2 % of the
      world population. Age of onset is generally between 20 and 30 years of age with a
      chronic, unremitting course for the duration of the patient's life. Although
      schizophrenia is among the most severe and debilitating illnesses known to
      medicine, its treatment has remained virtually unchanged for over 50 years. This
      chapter covers several major concepts in experimental drug development and
      delivery: (1) the concept of "typical" vs. "atypical" classifications for
      antipsychotic drugs as it relates to dosing; (2) the development of depot
      formulations for improved medication adherence; and (3) several promising areas
      for future therapeutic advances related to the methods and duration of drug
      administration. These areas include sublingual, injectable, and implantable drug
      delivery strategies that have the potential to effect rapid and dramatic
      improvements in schizophrenia outcomes.

PMID- 23129337
TI  - Imaging as tool to investigate psychoses and antipsychotics.
AB  - The results of imaging studies have played an important role in the formulation
      of hypotheses regarding the etiology of psychosis and schizophrenia, as well as
      in our understanding of the mechanisms of action of antipsychotics. Since this
      volume is primarily directed to molecular aspects of psychosis and
      antipsychotics, only the results of molecular imaging techniques addressing these
      topics will be discussed here.One of the most consistent findings of molecular
      imaging studies in schizophrenia is an increased uptake of DOPA in the striatum,
      which may be interpreted as an increased synthesis of L-DOPA. Also, several
      studies reported an increased release of dopamine induced by amphetamine in
      schizophrenia patients. These findings played an important role in reformulating
      the dopamine hypothesis of schizophrenia. To study the roles of the
      neurotransmitters gamma-aminobutyric acid (GABA) and glutamate in schizophrenia,
      SPECT as well as MR spectroscopy have been used. The results of preliminary SPECT
      studies are consistent with the hypothesis of NMDA receptor dysfunction in
      schizophrenia. Regarding the GABA deficit hypothesis of schizophrenia, imaging
      results are inconsistent. No changes in serotonin transporters were demonstrated
      in imaging studies in schizophrenia, but studies of several serotonin receptors
      showed conflicting results. The lack of selective radiotracers for muscarinic
      receptors may have hampered examination of this system in schizophrenia as well
      as its role in the induction of side effects of antipsychotics. Interestingly,
      preliminary molecular imaging studies on the cannabinoid-1 receptor and on
      neuroinflammatory processes in schizophrenia have recently been published.
      Finally, a substantial number of PET/SPECT studies have examined the occupancy of
      receptors by antipsychotics and an increasing number of studies is now focusing
      on the effects of these drugs using techniques like spectroscopy and
      pharmacological MRI.

PMID- 23129338
TI  - Biomarkers for antipsychotic therapies.
AB  - Molecular biomarkers for antipsychotic treatments have been conceptually linked
      to the measurements of dopamine functions, mostly D(2) receptor occupancy, either
      by imaging using selective PET/SPECT radioactive tracers or by assessing plasma
      prolactin levels. A quest for novel biomarkers was recently proposed by various
      academic, health service, and industrial institutions driven by the need for
      better treatments of psychoses. In this review we conceptualize biomarkers within
      the Translational Medicine paradigm whose goal was to provide support to critical
      decision-making in drug discovery. At first we focused on biomarkers as outcome
      measure of clinical studies by searching into the database clinicaltrial.gov. The
      results were somewhat disappointing, showing that out of 1,659 antipsychotic
      trials only 18 used a biomarker as an outcome measure. Several of these trials
      targeted plasma lipids as sentinel marker for metabolic adverse effects
      associated with the use of atypical antipsychotics, while only few studies were
      aimed to new disease specific biological markers. As an example of a mechanistic
      biomarker, we described the work done to progress the novel class of glycine
      transporter inhibitors as putative treatment for negative symptoms of
      schizophrenia. We also review how large-scale multiplex biological assays were
      applied to samples from tissues of psychiatric patients, so to learn from changes
      of numerous analytes (metabolic products, lipids, proteins, RNA transcripts)
      about the substrates involved in the disease. We concluded that a stringent
      implementation of these techniques could contribute to the endophenotypic
      characterization of patients, helping in the identification of key biomarkers to
      drive personalized medicine and new treatment development.

PMID- 23129339
TI  - Behavioral animal models of antipsychotic drug actions.
AB  - Basic research in animals represents a fruitful approach to study the
      neurobiological basis of brain and behavioral disturbances relevant to
      neuropsychiatric disease and to establish and evaluate novel pharmacological
      therapies for their treatment. In the context of schizophrenia, there are models
      employing specific experimental manipulations developed according to specific
      pathophysiological or etiological hypotheses. The use of selective lesions in
      adult animals and the acute administration of psychotomimetic agents are
      indispensable tools in the elucidation of the contribution of specific brain
      regions or neurotransmitters to the genesis of a specific symptom or collection
      of symptoms and enjoy some degrees of predictive validity. However, they may be
      inaccurate, if not inadequate, in capturing the etiological mechanisms or
      ontology of the disease needed for a complete understanding of the disease and
      may be limited in the discovery of novel compounds for the treatment of negative
      and cognitive symptoms of schizophrenia. Under the prevailing consensus of
      schizophrenia as a disease of neurodevelopmental origin, we have seen the
      establishment of neurodevelopmental animal models which aim to identify the
      etiological processes whereby the brain, following specific triggering events,
      develops into a "schizophrenia-like brain" over time. Many neurodevelopmental
      models such as the neonatal ventral hippocampus (vHPC) lesion,
      methylazoxymethanol (MAM), and prenatal immune activation models can mimic a
      broad spectrum of behavioral, cognitive, and pharmacological abnormalities
      directly implicated in schizophrenic disease. These models allow pharmacological
      screens against multiple and coexisting schizophrenia-related dysfunctions while
      incorporating the disease-relevant concept of abnormal brain development. The
      multiplicity of existing models is testimonial to the multifactorial nature of
      schizophrenia, and there are ample opportunities for their integration. Indeed,
      one ultimate goal must be to incorporate the successes of distinct models into
      one unitary account of the complex disorder of schizophrenia and to use such
      unitary approaches in the further development and evaluation of novel
      antipsychotic treatment strategies.

PMID- 23129340
TI  - Lung function outcome at school age in very low birth weight children.
AB  - OBJECTIVE: The aim of this study was to assess pulmonary function and its
      predictors in very low birth weight (birth weight <=1,500 g) children (VLBWc)
      with or without bronchopulmonary dysplasia (BPD), born at gestational age <=32
      weeks at a single tertiary center during 1996-1999, after the introduction of
      surfactant therapy. METHODS: Of the 120 surviving VLBW children, 48 (40%) VLBWc
      (22 with prior-BPD) at age 8.5 +/- 1.0 years and 46 age-matched controls (8.8 +/-
      1.4 years) born at term, underwent lung function study. RESULTS: Adjusted values
      (z-score) of forced vital capacity (z-FVC), forced expiratory volume in 1 sec (z
      FEV1), forced expiratory flow 25-75% (z-FEF25-75), carbon monoxide lung diffusion
      capacity (z-DLCO), and DLCO/alveolar volume (z-DLCO/VA) were significantly lower
      than controls (mean difference, 95% CI: -1.35, -1.81 to -0.90, P < 0.001; -1.31, 
      1.73 to -0.90, P < 0.001; -0.87, -1.29 to -0.46, P < 0.001; -0.98, -1.72 to 
      0.23, P < 0.001; -0.70, -1.22 to -0.18, P < 0.05; respectively). Residual volume
      (z-RV) and RV/total lung capacity (RV/TLC) ratio (%) were significantly higher in
      VLBWc than controls (mean difference, 95% CI: 1.06, 0.44 to 1.68, P < 0.001;
      9.54%, 5.73 to 13.3%, P < 0.001; respectively). No differences were found in lung
      function between VLBWc (no-BPD vs. BPD) with the exception of a significant
      higher RV/TLC ratio in the BPD-subgroup (mean difference, 95% CI: 7.0%, 0.4 to
      13%, P = 0.03). Lung function abnormalities were found in 30 (63%) VLBWc with
      evidence of airway obstruction and diffusing capacity impairment. A weak
      relationship was observed between gestational age with z-FVC (r = 0.30, P =
      0.04), birth weight with z-FEV1 (r = 0.30, P = 0.04) and RV/TLC ratio (r = -0.49,
      P = 0.001). The duration of oxygen treatment correlated negatively with the z
      DLCO/Va (r = -0.5, P = 0.02). No differences were found in FeNO levels between
      VLBWc and controls. CONCLUSION: VLBWc at school age showed lung function
      abnormalities characterized by airway obstruction, hyperinflation, and diffusion
      impairment. Neonatal lung damage together with preterm birth may play a role in
      worsening the functional respiratory outcome.

PMID- 23129341
TI  - Nichotherapy for stem cells: there goes the neighborhood.
AB  - Stem cells and their malignant counterparts require the support of a specific
      microenvironment or "niche". While various anti-cancer therapies have been
      broadly successful, there are growing opportunities to target the environment in
      which these cells reside to further improve therapeutic efficacy and outcome.
      This is particularly true when the aim is to target normal or malignant stem
      cells. The field aiming to target or use the niches that harbor, protect, and
      support stem cells could be designated as "nichotherapy". In this essay, we
      provide a few examples of nichotherapies. Some have been employed for decades,
      such as hematopoietic stem cell mobilization, whereas others are emerging, such
      as chemosensitization of leukemia stem cells by targeting their niche.

PMID- 23129342
TI  - Regulation of human Cripto-1 expression by nuclear receptors and DNA promoter
      methylation in human embryonal and breast cancer cells.
AB  - Human Cripto-1 (CR-1) plays an important role in regulating embryonic development
      while also regulating various stages of tumor progression. However, mechanisms
      that regulate CR-1 expression during embryogenesis and tumorigenesis are still
      not well defined. In the present study, we investigated the effects of two
      nuclear receptors, liver receptor homolog (LRH)-1 and germ cell nuclear factor
      receptor (GCNF) and epigenetic modifications on CR-1 gene expression in NTERA-2
      human embryonal carcinoma cells and in breast cancer cells. CR-1 expression in
      NTERA-2 cells was positively regulated by LRH-1 through direct binding to a DR0
      element within the CR-1 promoter, while GCNF strongly suppressed CR-1 expression
      in these cells. In addition, the CR-1 promoter was unmethylated in NTERA-2 cells,
      while T47D, ZR75-1, and MCF7 breast cancer cells showed high levels of CR-1
      promoter methylation and low CR-1 mRNA and protein expression. Treatment of
      breast cancer cells with a demethylating agent and histone deacetylase inhibitors
      reduced methylation of the CR-1 promoter and reactivated CR-1 mRNA and protein
      expression in these cells, promoting migration and invasion of breast cancer
      cells. Analysis of a breast cancer tissue array revealed that CR-1 was highly
      expressed in the majority of human breast tumors, suggesting that CR-1 expression
      in breast cancer cell lines might not be representative of in vivo expression.
      Collectively, these findings offer some insight into the transcriptional
      regulation of CR-1 gene expression and its critical role in the pathogenesis of
      human cancer.

PMID- 23129343
TI  - Polythiophene synthesis coupled to quartz crystal microbalance and Raman
      spectroscopy for detecting bacteria.
AB  - A simple electrochemical procedure was used for the synthesis of a polythiophene
      containing para-benzenesulfonyl chloride groups. The obtained polymer was shown
      to be very reactive and directly able to covalently bind nucleophile
      biomolecules. Protein A and a specific antibody were then successively
      immobilized on the conductive polymer through a covalent bonding of Protein A
      with the as-prepared linker for bacteria trapping purpose. All reactions were
      controlled in situ by cyclic voltammetry, quartz crystal microbalance and Raman
      spectroscopy. The results were compared to those previously obtained on gold
      surface modified with the same chemical linker. The conductive polymer led to a
      very high rate of antibody recognition compared to the gold surface and to
      literature, probably due to a large available surface obtained after
      polymerization. One example of pathogenic bacteria "Salmonella enterica
      paratyphi" detection was successfully tested on the substrates. The presented
      results are promising for the future design of simple and inexpensive
      immunocapture-based sensors.

PMID- 23129344
TI  - Therapy in pediatric stroke.
AB  - The aim of this review is to summarize the existing literature on therapy and
      management of cerebrovascular insults in children and adolescents. As data
      sources, studies were identified by MEDLINE, PubMed, Cochrane Library, and
      relevant bibliographies for the topic "pediatric stroke." We also reviewed
      guidelines for "stroke in adults." As a result, pediatric stroke is
      underestimated. The annual incidence for all stroke entities (cerebral venous
      thrombosis and hemorrhagic and arterial ischemic stroke) is as high as for
      pediatric brain tumors, 3-15/100.000 children per year. A distinct etiology can
      be determined only in a minority of them. Underlying risk factors are multiple,
      mainly vasculopathies, congential heart diseases, coagulopathies, lipometabolic
      disorders, and sickle cell anemia. Current recommendations for therapy are based
      on adult studies, are preliminary, and discussed controversially. Antithrombotic
      therapy is uniformly recommended for the acute stage of pediatric stroke; no
      consensus exists on antiplatelet therapy with acetylsalicylic acid (ASA, aspirin)
      (5 mg/d), with ultra-fractionated or low-molecular-weight heparin. Thrombolysis
      using recombinant tissue plasminogen activator is not advised, despite the fact
      that current practice takes a different approach. None of the guidelines specify
      the duration of ASA for secondary prevention. Additional supportive therapy
      measures are osmotherapy and decompressive craniectomy. Oxygen in the absence of
      hypoxemia, intensive insulin therapy, antiepileptic drugs in the absence of
      clinical or electrographic seizures, corticosteroids, and GP-IIb/IIIa-receptor
      antagonists should not be used outside clinical trials. In conclusions, current
      therapeutic guidelines for pediatric stoke are still based on consensus and
      expert and society opinions and differ between countries. Consensus prevails on
      the need for acute anticoagulation using either antiplatelets or heparin. Long
      term treatment with acetylsalicylic acid in all or only high-risk patients and
      for how long remains the subject of debate. Lifelong secondary prevention has
      never been investigated in children or adults. All guidelines agree that there is
      no indication for thrombolysis in children outside clinical trials, although
      clinical practice in large centers differs.

PMID- 23129345
TI  - Aeromonas cavernicola sp. nov., isolated from fresh water of a brook in a cavern.
AB  - Aeromonas P2973 was isolated from the water of a brook in a cavern in the Czech
      Republic. This isolate could not be biochemically identified at the species
      level, considering all updated species descriptions. Subsequent extensive
      phenotypic characterisation, DNA-DNA hybridisation, 16S rRNA gene sequencing and
      a Multi-Locus Phylogenetic Analysis (MLPA) of the concatenated sequence of 7
      housekeeping genes (gyrB, rpoD, recA, dnaJ, gyrA, dnaX and atpD; 4705 bp) was
      employed in an attempt to ascertain the taxonomy of this isolate. Based on this
      polyphasic approach, we describe a novel species of the genus Aeromonas, for
      which the name Aeromonas cavernicola sp. nov. is proposed, with strain CCM7641(T)
      (DSM24474(T), CECT7862(T)) as the type strain.

PMID- 23129346
TI  - Molecular characterization of plasmid pMbo4.6 of Moraxella bovis ATCC 10900.
AB  - We report the characterization of a small cryptic plasmid unlike any previously
      described from Moraxella bovis ATCC 10900, a Gram-negative bacterium belonging to
      the family Moraxellaceae. The complete nucleotide sequence of the plasmid pMbo4.6
      was determined. The plasmid was analyzed and found to be 4658 in size with a G+C
      content of 38.6 mol %. Computer analysis of the sequence data revealed four major
      open reading frames encoding putative proteins of 10.1 (ORF1), 64.2 (ORF2), 45.7
      (ORF3), and 12.1 kDa (ORF4). ORF1 and ORF2 encode proteins that show a high level
      of amino acid sequence similarity (44 %) with some mobilization proteins. ORF3
      encodes a protein showing a relatively high amino acid sequence similarity (about
      40 %) with several plasmid replication initiator proteins. Upstream of ORF3, a
      320-bp intergenic region, constituting the putative origin of replication that
      contained an AT-rich region followed by four direct repeats, was identified. This
      set of repeated sequences resembles iteron structures and plays an important role
      in the control of plasmid replication by providing a target site for the
      initiation of transcription and replication factors (IHF and RepA). Several
      palindromic sequences, inverted repeats, and hairpin-loop structures, which might
      confer regulatory effects on the replication of the plasmid, were also noted.
      ORF4 encodes an uncharacterized protein, conserved in bacteria, belonging to the
      DUF497 family. Sequence analysis and structural features indicate that pMbo4.6
      replicates by a theta mechanism.

PMID- 23129347
TI  - Hypofractionated stereotactic radiotherapy and continuous low-dose temozolomide
      in patients with recurrent or progressive malignant gliomas.
AB  - To evaluate the efficacy of reirradiation and systemic chemotherapy as salvage
      treatment in patients with recurrent malignant glioma. Between May 2006 and
      December 2011, 54 patients with recurrent malignant glioma received
      hypofractionated stereotactic radiotherapy (HSRT) plus systemic therapy at
      University of Rome Sapienza, Sant' Andrea Hospital. All patients had Karnofsky
      performance score >=60 and were previously treated with standard conformal RT (60
      Gy) with concomitant and adjuvant temozolomide (TMZ) up to 12 cycles. Thirty
      eight patients had a GBM and 16 patients had a grade 3 glioma. The median time
      interval between primary RT and reirradiation was 15.5 months. At the time of
      recurrence all patients received HSRT (30 Gy in 6-Gy fractions) plus concomitant
      TMZ (75 mg/m(2)/day) followed by continuous TMZ at 50 mg/m(2) everyday up to 1
      year or until progression. Median overall survival after HSRT was 12.4 months,
      and the 12- and 24-month survival rates were 53 and 16 %, respectively. The
      median progression-free survival (PFS) was 6 months, and the 12- and 24-month PFS
      rates were 24 and 10 %, respectively. KPS >70 (P = 0.04) and grade 3 glioma were
      independent favourable prognostic factors for survival. In general chemoradiation
      regimen was well tolerated with relatively low treatment-related toxicity. HSRT
      plus concomitant TMZ followed by continuous dose-intense TMZ is a feasible
      treatment option associated with survival benefits and low risk of complications
      in selected patients with recurrent malignant glioma. The potential advantages of
      combined chemoradiation schedules in patients with recurrent malignant gliomas
      need to be explored in future studies.

PMID- 23129348
TI  - Assessment of human health risks from heavy metals in outdoor dust samples in a
      coal mining area.
AB  - Jharia (India) a coal mining town has been affected by the consequences of mining
      and associated activities. Samples of outdoor fallen dust were collected at
      different locations of Jharia covering four different zones: commercial, petrol
      pump, high traffic, and residential areas. The dust samples were analysed for
      different trace elements (As, Cd, Co, Cr, Cu, Mn, Ni, Pb, Se, and Zn). The
      highest concentration of the elements in the dust samples are Mn (658 mg/kg), Zn
      (163.6 mg/kg), Cr (75.4 mg/kg), Pb (67.8 mg/kg), Ni (66 mg/kg), Cu (56.8 mg/kg),
      Co (16.9 mg/kg), As (4.1 mg/kg), and Cd (0.78 mg/kg). The concentration of
      selenium was below detection limit. Except Cd, contents of all the other elements
      in the dust samples were significantly lower in the residential area. High amount
      of Ni (145 mg/kg) and Pb (102 mg/kg) was observed in the high traffic and petrol
      pump areas, respectively. The exposure risk assessment strategies are helpful in
      predicting the potential health risk of the trace elements in the street dust.
      Selected receptors for risk assessment were infants, toddlers, children, teens,
      and adults. The calculated hazard quotient (HQ) for lifetime exposure was <1.0
      for all the elements studied, indicating no risks from these elements for adults
      Among the receptors, toddlers were found to be more vulnerable, with HQ for Co,
      Cr, and Pb > 0.1. The finding predicts potential health risk to toddlers and
      children.

PMID- 23129349
TI  - Periodic modulations of optical tweezers near solid-state membranes.
AB  - Optical tweezers operated near solid-state membranes show unexplained periodic
      modulations in the optical trap position. An experimental study of the
      oscillations is presented, as well as optical simulations based on the finite
      difference time-domain method, providing insight into the underlying interference
      phenomenon. This work provides a complete description as well as a solution to
      the enduring problem of modulations in optical traps near solid-state membranes.

PMID- 23129350
TI  - Catalytic electron-transfer oxygenation of substrates with water as an oxygen
      source using manganese porphyrins.
AB  - Manganese(V)-oxo-porphyrins are produced by the electron-transfer oxidation of
      manganese-porphyrins with tris(2,2'-bipyridine)ruthenium(III) ([Ru(bpy)(3)](3+);
      2 equiv) in acetonitrile (CH(3)CN) containing water. The rate constants of the
      electron-transfer oxidation of manganese-porphyrins have been determined and
      evaluated in light of the Marcus theory of electron transfer. Addition of
      [Ru(bpy)(3)](3+) to a solution of olefins (styrene and cyclohexene) in CH(3)CN
      containing water in the presence of a catalytic amount of manganese-porphyrins
      afforded epoxides, diols, and aldehydes efficiently. Epoxides were converted to
      the corresponding diols by hydrolysis, and were further oxidized to the
      corresponding aldehydes. The turnover numbers vary significantly depending on the
      type of manganese-porphyrin used owing to the difference in their oxidation
      potentials and the steric bulkiness of the ligand. Ethylbenzene was also oxidized
      to 1-phenylethanol using manganese-porphyrins as electron-transfer catalysts. The
      oxygen source in the substrate oxygenation was confirmed to be water by using
      (18)O-labeled water. The rate constant of the reaction of the manganese(V)-oxo
      species with cyclohexene was determined directly under single-turnover conditions
      by monitoring the increase in absorbance attributable to the manganese(III)
      species produced in the reaction with cyclohexene. It has been shown that the
      rate-determining step in the catalytic electron-transfer oxygenation of
      cyclohexene is electron transfer from [Ru(bpy)(3)](3+) to the manganese
      porphyrins.

PMID- 23129351
TI  - Ephrin-B stimulation of calvarial bone formation.
AB  - INTRODUCTION: Ephrin-B2 on osteoclasts was reported to promote bone formation as
      part of homeostasis by activating the EphB4 tyrosine kinase receptor on
      osteoblasts. Little is known about the role of ephrin-B signaling to EphBs in
      developmental bone formation. RESULTS: We observed expression of an ephrin-B2
      LacZ chimeric allele in the periosteum, sutural bone fronts, and dura mater of
      embryonic and neonatal mice. Expression in the adult skull was confined to
      sutures, but was heavily upregulated at sites of bone injury. Culture of
      embryonic calvariae with soluble recombinant ephrin-B2/Fc doubled their bone
      content without altering suture width or overall skull morphology. Ephrin-B2/Fc
      also stimulated osteoblast marker gene expression in cultured MC3T3
      preosteoblastic cells without the need for type 1 collagen-induced
      differentiation. EphB4 was absent in embryonic and adult skulls. However, EphB1
      and EphB2, both physiological receptors for ephrin-Bs, were expressed at sites of
      osteogenesis, and EphB1 knockout mice displayed a reduction in calvarial bone
      content compared to controls. CONCLUSIONS: These data support a role for ephrin
      B2 in the development and healing of bone through activation of osteoblast
      specific gene expression. EphB1 and EphB2 are likely candidates receptors for the
      ephrin-B2 in bone.

PMID- 23129352
TI  - Ventricular assist devices: is destination therapy a viable alternative in the
      non-transplant candidate?
AB  - The topic of this article, stated a more familiar way, is whether left
      ventricular assist devices (LVADs) are ready for 'Primetime' as a therapeutic
      option in and of themselves. In order to provide an update and insight on this
      question, we briefly review from where the field has come, and in more detail
      describe its current state and where we are heading. We believe the short answer
      to this question is 'Yes', but like many things, a short answer is not adequate.
      Here we attempt to deliver a more comprehensive answer, providing some historical
      context, outlining the great achievements that have been made, as well as the
      many challenges that still remain before LVADs become a truly mainstream therapy.

PMID- 23129353
TI  - Catastrophic ascending aortic graft thrombosis.

PMID- 23129354
TI  - Advanced practitioners in the cardiothoracic intensive care unit.

PMID- 23129355
TI  - Is MitraClip therapy really an alternative therapeutic option in functional
      mitral regurgitation when compared with ring annuloplasty?

PMID- 23129356
TI  - Impact of interstitial lung disease on short-term and long-term survival of
      patients undergoing surgery for non-small-cell lung cancer: analysis of risk
      factors.
AB  - OBJECTIVES: The study aimed to determine the impact of interstitial lung disease
      (ILD) on postoperative morbidity, mortality and long-term survival of patients
      with non-small-cell lung cancer (NSCLC) undergoing pulmonary resection. METHODS:
      We performed a retrospective chart review of 775 consecutive patients who had
      undergone lung resection for NSCLC between 2000 and 2009. ILD, defined by medical
      history, physical examination and abnormalities compatible with bilateral lung
      fibrosis on high-resolution computed tomography, was diagnosed in 37 (4.8%)
      patients (ILD group). The remaining 738 patients were classified as non-ILD
      (control group). We also attempted to identify the predictive factors for early
      and late survival in patients with ILD following pulmonary resection. RESULTS:
      There was no significant difference between the two groups in terms of age (69 vs
      66 years), sex (79 vs 72% male), smoking history (93 vs 90% smokers), forced
      expiratory volume in 1 s % of predicted (89 vs 84%), predicted values of forced
      vital capacity (FVC)% (92 vs 94%), types of surgical resection and histology.
      Patients with ILD had a higher incidence of postoperative acute respiratory
      distress syndrome (ARDS; 13 vs 1.8%, P < 0.01) and higher postoperative mortality
      (8 vs 1.4%, P < 0.01). The overall 5-year survival rate was 52% in the ILD and
      65% in the non-ILD patients, respectively (P = 0.019). In the ILD group, at the
      median follow-up of 26 months (range 4-119), 19 (51%) patients were still alive
      and 18 (49%) had died in the ILD group. The major cause of late death was
      respiratory failure due to the progression of fibrosis (n = 7, 39%). In the ILD
      group, lower preoperative FVC% (mean 77 vs 93%, P < 0.01) and lower diffusing
      capacity of the lung for carbon monoxide (DLCO%; 47 vs 62%; P < 0.01) were
      significantly associated with postoperative ARDS. CONCLUSIONS: In conclusion,
      major lung resection in patients with NSCLC and ILD is associated with an
      increased postoperative morbidity and mortality. Patients with a low preoperative
      FVC% should be carefully assessed prior to undergoing surgery, particularly in
      the presence of a lower DLCO%. Long-term survival is significantly lower when
      compared with patients without ILD, but still achievable in a substantial
      subgroup. Thus, surgery can be offered to properly selected patients with lung
      cancer and ILD, keeping in mind the risk of respiratory failure during the
      evaluation of such patients.

PMID- 23129357
TI  - Monitoring of regional tissue oxygenation with near-infrared spectroscopy during
      the early postoperative course after superior cavopulmonary anastomosis.
AB  - OBJECTIVES: Near-infrared spectroscopy (NIRS) offers continuous non-invasive
      monitoring of regional tissue oxygenation. We evaluated NIRS monitoring during
      the postoperative course after superior cavopulmonary anastomosis in patients
      with hypoplastic left heart syndrome and anatomically related malformations.
      METHODS: Cerebral (cSO(2)) and somatic (sSO(2)) tissue oxygenations were recorded
      for 48 h and compared with routine measures of intensive care monitoring. Changes
      in parameters in the case of postoperative complications were evaluated. RESULTS:
      Data were obtained from 32 patients. Median age at operation was 2.9 (1.5-10.0)
      months and weight was 5.3 +/- 1.0 kg. Postoperative complications occurred in 7
      patients (pulmonary artery thrombus n = 4, pneumothorax n = 1, cardiopulmonary
      resuscitation n = 1 and low-cardiac output n = 1). cSO(2) was 44 +/- 14% at the
      end of the operation and reached its minimum of 40 +/- 11% 2 h later (P = 0.018).
      Overall, cSO(2) was depressed early after surgery and increased from a mean of 42
      +/- 11% during the first 4 postoperative hours to 57 +/- 8% in the last 4 h of
      the study period (P < 0.001). The sSO(2) decreased from 77 +/- 11% during the
      early postoperative course to 68 +/- 9% within the later course (P < 0.001). The
      cSO(2) correlated with the arterial partial pressure of oxygen (pO(2), r = 0.364,
      P < 0.001), with the arterial oxygen saturation (SaO(2), r = 0.547, P < 0.001)
      and with the central venous oxygen saturation providing the strongest correlation
      (SvO(2), r = 0.686, P < 0.001). Analysis of agreement between cSO(2) and SvO(2)
      measurements revealed a mean bias of 0.97 with limits of agreement between 19.8
      and -17.9%. Inclusion of both cSO(2) and sSO(2) into a linear regression model
      slightly improved the prediction of SvO(2) from NIRS values (r = 0.706, P <
      0.001). The mean values of cSO(2), sSO(2), SaO(2) and SvO(2) during the early
      postoperative period were lower in patients with complications (cSO(2): 45 +/- 9
      vs 29 +/- 5%, P < 0.001; sSO(2): 80 +/- 11 vs 70 +/- 6%, P = 0.004; SaO(2): 76 +/
      8 vs 66 +/- 6%, P = 0.004; SvO(2): 48 +/- 14 vs 32 +/- 6%, P < 0.001).
      CONCLUSIONS: NIRS technology allows inferring the global oxygenation from
      continuous non-invasive measurements of regional tissue oxygenation. The cSO(2)
      is lowered in the early postoperative course. Lower cSO(2) values in the early
      postoperative course may be predictive of postoperative complications.

PMID- 23129358
TI  - Limited resection for clinical Stage IA non-small-cell lung cancers based on a
      standardized-uptake value index.
AB  - OBJECTIVES: In a previous study, we found that a standardized-uptake value (SUV)
      index obtained from positron emission tomography (PET)/computed tomography (CT)
      data was significantly correlated with prognosis in patients with pathological
      Stage I lung adenocarcinoma. However, this value has not been studied in early
      stage lung cancer patients undergoing limited resection. In this study, we
      investigated if an SUV index could be used to identify patients with clinical
      Stage IA lung cancers that were appropriate for limited resection. METHODS: This
      was a retrospective study of prospectively collected data from 183 patients with
      clinical Stage IA non-small-cell lung cancer undergoing both PET-CT examinations
      and surgery from May 2004 to December 2010. A corrected SUV was defined as the
      SUV index, which was calculated from the ratio of the tumour SUV(max) to the
      liver SUV(mean). The associations between survival, recurrence and several
      clinical factors, including the SUV index, were evaluated. RESULTS: The following
      pathological stages were identified: Stage IA (n = 133; 72.7%), Stage IB (n = 31;
      16.9%), Stage IIA (n = 11; 6.0%), Stage IIB (n = 1; 0.5%) and Stage IIIA (n = 7;
      3.8%). There were 50 upstaged cases (27.3%). The 5-year overall survival, 5-year
      cancer-specific survival and 5-year freedom from recurrence (FFR) rates after
      surgery were 83.5, 91.6 and 83.1%, respectively. Twenty-six (14.2%) patients
      developed recurrences. Multivariate analysis showed that an SUV index was a
      significant predictive factor for recurrence (P = 0.01). The 5-year FFR rates in
      patients with an SUV indices <1.0 and >=1.0 were 100 and 77.1%, respectively (P <
      0.01). The 5-year cancer-specific survival rates in patients with an SUV indices
      <1.0 and >=1.0 were 100 and 88.7%, respectively (P = 0.04). CONCLUSIONS: In
      clinical Stage IA lung cancer patients, the SUV index was a significant
      predictive marker for recurrence. Patients with SUV indices <1.0 were less likely
      to have a recurrence. Thus, clinical Stage IA patients with SUV indices <1.0
      should be candidates for limited resection.

PMID- 23129359
TI  - A simple technique for marking the aortic annulus during the implantation of a
      stentless aortic bioprosthesis.

PMID- 23129360
TI  - Correlation between cystometric volumes, ATP release, and pH in women with
      overactive bladder versus controls.
AB  - AIMS: In the bladder, ATP is an important signaling molecule, which is released
      by bladder stretch and acid. We hypothesized that ATP might play a unique role in
      patients with OAB, characterized by low bladder volumes at first desire to void
      (FDV) and maximal cystometric capacity (MCC) and symptoms of frequency/urgency
      [mild bladder pain syndrome (BPS)]. Our aim was to investigate the correlation
      between ATP release and urodynamic parameters, as well as urine pH, in OAB
      patients. METHODS: Routine cystometry was performed in a consecutive series of
      249 women. The voided urodynamic fluid (VUF) was stored at -20 degrees C and ATP
      measured using bioluminescence. Catheter urine was collected for pH measurement.
      Correlations between two factors were tested by linear regression analysis.
      RESULTS: Subjects with urinary tract infection, voiding dysfunction, and detrusor
      overactivity (DO) were excluded. For OAB patients (n = 25), there was an inverse
      correlation between ATP concentration in VUF and FDV (r(2)  = 0.25; P = 0.01) but
      not MCC. This was not seen in controls (n = 69). In OAB, but not controls, there
      was a significant reverse correlation (r(2)  = 0.16; P = 0.047) between ATP in
      VUF and urine pH. Urine pH was not significantly correlated with MCC in either
      group. CONCLUSIONS: In OAB patients, ATP is an important factor for initial
      perception of need to urinate (as indicated by FDV). This is similar to our
      previous findings in patients with DO, suggesting that ATP may mediate initial
      afferent sensation in patients with bladder dysfunctions characterized by
      urgency. ATP release was also strongly affected by urine pH, in patients with OAB
      (at FDV).

PMID- 23129361
TI  - Transition-metal-free aerobic oxidative cleavage of C-C bonds in alpha-hydroxy
      ketones and mechanistic insight to the reaction pathway.
AB  - Clear cut: For the title reaction, O(2), the ideal oxidant, was used as the only
      oxidizing reagent. The dimer intermediate (see scheme) and isotopic labeling
      control experiments with (18)O(2) partially disclosed the reaction mechanism.

PMID- 23129362
TI  - Peroxisome proliferator-activated receptor-gamma cofactors in neurodegeneration.
AB  - Peroxisome proliferator-activated receptor-gamma (PPARgamma) was initially
      involved in the regulation of glucose and lipid metabolism, cell differentiation,
      as well as in the transcriptional control of a wide range of inflammatory genes.
      However, during the last decade, there has been evidence of the implication of
      this nuclear receptor in neurodegeneration. Various studies have shown that the
      administration of PPARgamma ligands leads to a reduced pathology in many
      neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease,
      amyotrophic lateral sclerosis, multiple sclerosis, Huntington's disease, and
      stroke. PPARgamma cofactors have a critical function in regulating the activity
      of PPARgamma. Recent reports have brought to light the role of the PPARgamma
      coactivator-1alpha (PGC-1alpha) in several neurodegenerative pathologies.
      However, very little is know about other PPARgamma cofactors in the brain, such
      as the receptor-interacting protein 140, as well as the nuclear receptor
      corepressor, which seems to be required for normal neural development at specific
      embryonic stages. In this review, we aim to analyze the role of the main
      regulators of PPARgamma in the brain and during neurodegeneration.

PMID- 23129363
TI  - Clinically relevant study end points in rectal cancer.
AB  - In rectal cancer currently there are no clearly validated early end points which
      can serve as surrogates for long-term clinical outcome such as local control and
      survival. However, the use of a variety of response rates (i.e. pathological
      complete response, downsizing the primary tumor, tumor regression grade (TRG),
      radiological response) as endpoints in early (phase II) clinical trials is common
      since objective response to therapy is an early indication of activity. Disease
      free survival (DFS) has been proposed as the most appropriate end point in
      adjuvant trials and is one of the most frequently used in newer rectal cancer
      trials. Due to the devastating nature of local recurrence in locally advanced
      rectal cancer, local control (which is itself a subset of the overall DFS
      endpoint) is still considered an important endpoint. Recently, circumferential
      resection margin (CRM) has been proposed as novel early end point because the CRM
      status can account for effects on DFS and overall survival after chemoradiation,
      radiation (RT), or surgery alone. Consensus is needed to define the most
      appropriate end points in both early and phase III trials in locally advanced
      cancer.

PMID- 23129364
TI  - Neoadjuvant treatment in rectal cancer: do we always need radiotherapy-or can we
      risk assess locally advanced rectal cancer better?
AB  - There is good quality evidence that preoperative radiotherapy reduces local
      recurrence but there is little impact on overall survival. This is not completely
      unexpected as radiotherapy is a localised treatment and local control may not
      prevent systemic failure. Optimal quality-controlled surgery for patients with
      operable rectal cancer in the trial setting can be associated with local
      recurrence rates of less than 10 % whether patients receive radiotherapy or not
      (Quirke et al. 2009). However, despite the reassuring results of randomised
      trials, concerns remain that radiotherapy increases surgical morbidity
      (Horisberger et al. 2008; Stelzmueller et al. 2009; Swellengrebel et al. 2011),
      which can compromise the delivery of postoperative adjuvant chemotherapy. There
      are also significant late effects from pelvic radiotherapy (Peeters et al. 2005;
      Lange et al. 2007) and a risk of second malignancies (Birgisson et al. 2005; van
      Gijn et al. 2011). If preoperative radiotherapy does not impact on survival, can
      it be omitted in selected cases? The answer is yes-with the proviso that we are
      using good quality magnetic resonance imaging and good quality TME surgery within
      the mesorectal plane and the predicted risk of subsequent metastatic disease
      justifies its use. In this case, the concept of neoadjuvant chemotherapy (NACT)
      is a potentially attractive alternative strategy which might have less early and
      long-term side effects compared to preoperative radiotherapy-particularly where
      the MRI predicts a high risk of metastatic disease in the context of a modest
      risk of local recurrence. This chapter discusses a more precise method of risk
      categorisation for locally advanced rectal cancer, and discusses possible options
      for neoadjuvant chemotherapy (NACT).

PMID- 23129365
TI  - Treatment dilemmas in patients with synchronous colorectal liver metastases.
AB  - Approximately 20 % of patients with colorectal cancer have synchronous liver
      metastases at the time of diagnosis. In some instances it is difficult to
      determine the best treatment strategy in these patients. For example, should the
      primary tumor be removed in those patients with unresectable liver metastases and
      who do not have any symptoms of the primary tumor? Or which operation should be
      performed first in patients with rectal cancer and synchronous resectable liver
      metastases? Unfortunately, there are no clear answers to these questions from
      prospective randomized trials. In the present article retrospective studies are
      analyzed in order to define the best possible treatment strategy for patients
      with synchronous colorectal liver metastases.

PMID- 23129366
TI  - Pancreatic surgery: beyond the traditional limits.
AB  - Pancreatic cancer is one of the five leading causes of cancer death for both
      males and females in the western world. More than 85 % pancreatic tumors are of
      ductal origin but the incidence of cystic tumors such as intrapapillary mucinous
      tumors (IPMN) or mucinous cystic tumors (MCN) and other rare tumors is rising.
      Complete surgical resection of the tumor is the mainstay of any curative
      therapeutic approach, however, up to 40 % of patients with potentially resectable
      pancreatic cancer are not offered surgery. This is despite 5-year survival rates
      of up to 40 % or even higher in selected patients depending on tumor stage and
      histology. Standard procedures for pancreatic tumors include the Kausch-Whipple-
      or pylorus-preserving Whipple procedure, and the left lateral pancreatic
      resection (often with splenectomy), and usually include regional lymphadenectomy.
      More radical or extended pancreatic operations are becoming increasingly utilised
      however and we examine the data available for their role. These operations
      include major venous and arterial resection, multivisceral resections and surgery
      for metastatic disease, or palliative pancreatic resection. Portal vein resection
      for local infiltration with or without replacement graft is now well established
      and does not deleteriously affect perioperative morbidity or mortality. Arterial
      resection, however, though often technically feasible, has questionable oncologic
      impact, is not without risk and is usually reserved for isolated cases. The value
      of extended lymphadenectomy is frequently debated; the recent level I evidence
      demonstrates no advantage. Multivisceral resections, i.e. tumors, often in the
      tail of the pancreas, with invasion of the colon or stomach or other surrounding
      tissues, while associated with an increased morbidity and a longer hospital stay,
      do however show comparable mortality-and survival rates to those without such
      infiltration and therefore should be performed if technically feasible. Routine
      resection for metastatic disease however does not seem to show any advantage over
      palliative treatment but may be an option in selected patients with easily
      removable metastases. In conclusion pancreatic surgery beyond the traditional
      limits is established in tumors infiltration the venous system and may be a
      considered approach in selected patients with locally infiltrating pancreatic
      cancer or metastasis.

PMID- 23129367
TI  - Adjuvant therapy for pancreatic cancer.
AB  - Pancreatic cancer is a challenging malignancy to treat, as less than one-fifth of
      diagnosed cases are resectable, surgery is complex and postoperative recovery
      slow, treated patients tend to relapse and overall survival rates are low. It is
      one of the leading causes of cancer-related mortality. Adjuvant therapy has been
      employed in resectable disease, to target micrometastases and improve prognosis.
      Chemotherapy, chemoradiotherapy (chemoRT) and chemoradiotherapy (chemoRT)
      followed on by chemotherapy have been evaluated in randomised controlled trials.
      The European Study Group for Pancreatic Cancer (ESPAC)-1 and CONKO-001 trials
      clearly established the survival advantage of adjuvant chemotherapy with 5
      fluorouracil (5FU) plus folinic acid and gemcitabine respectively over no
      chemotherapy. The ESPAC-3 (version 2) trial demonstrated equivalence between 5FU
      plus folinic acid and gemcitabine in terms of survival parameters, though
      gemcitabine had a better toxicity profile. The results of these key studies,
      together with smaller ones have been subjected to meta-analyses, with
      confirmation of improved survival with adjuvant systemic chemotherapy. The EORTC
      40891 and ESPAC-1 trials found no survival advantage with adjuvant chemoRT
      compared to observation, and this has been reflected in a subsequent meta
      analysis. The popularisation of chemoRT, with follow on chemotherapy (versus
      observation) was based on the small underpowered GITSG trial. The ESPAC-1 trial
      was unable to find a survival benefit for chemoRT, with follow on chemotherapy
      compared to observation. The RTOG-9704 trial assessed chemoRT with follow on
      chemotherapy in both arms and found no difference between survival in the
      gemcitabine and 5FU arms. There has never been a published head-to-head
      randomised comparison of adjuvant chemotherapy to chemoRT, with follow on
      chemotherapy. Ongoing randomised trials are looking into adjuvant combination
      chemotherapy, chemotherapy with follow on chemoRT, and neoadjuvant therapy. Novel
      agents continue to be assessed in early phase trials with a major emphasis on
      predictive and prognostic biomarkers. Based on the available evidence, adjuvant
      chemotherapy with gemcitabine or 5FU/folinic acid is the current recommended gold
      standard in the management of resected pancreatic cancer.

PMID- 23129368
TI  - Radiotherapy of the pancreas: state of the art in 2012.

PMID- 23129369
TI  - Adenocarcinoma of the GEJ: gastric or oesophageal cancer?
AB  - According to WHO (2010) adenocarcinomas of the esophagogastric junction (GEJ) are
      defined as tumors that cross the most proximal extent of the gastric folds
      regardless of where the bulk of the tumor lies. In addition, these neoplasms are
      now classified as esophageal cancers by UICC (2010). Recent studies, however,
      revealed two types of carcinogenesis in the distal oesophagus and at the GEJ, one
      of intestinal type (about 80 %) and the other of gastric type (about 20 %). These
      are characterized by marked differences in morphology, tumor stage at diagnosis,
      and prognosis. Furthermore, both cancer types show different targetable biomarker
      expression profiles such as Her2 in the intestinal and EGFR in the non-intestinal
      pathway indicating new therapy options. Due to the fact that carcinomas of the
      intestinal pathway were typically associated with Barrett's mucosa which was not
      the case in the non-intestinal-type tumors, this challenges the paradigm "no
      goblets no Barrett's". Moreover, even the cancer risk of intestinal-type
      metaplasia has seriously been questioned by a Danish population-based study where
      Barrett's mucosa turned out to be only a weak indicator of esophageal and GEJ
      cancer (1 case in 860 patients years). Thus, two biologically different types of
      cancer arise at the GEJ-esophageal and gastric type that open distinctive
      targeted treatment options and also question our current concept about the
      diagnostics of potential precursor lesions as well as the associated screening
      and surveillance strategy.

PMID- 23129370
TI  - Why is there a change in patterns of GE cancer?
AB  - Recent decades have seen a worrying trend in incidence rates of distal
      oesophageal and proximal gastric cancers. Fuelled by radical changes in
      lifestyle, diet, physical activity and environmental exposures, as well as an
      ageing population and host genetic predisposition, the incidence of oesophageal
      adenocarcinoma (OAC) is on the rise in Western populations. While overall
      incidence of gastric cancers is declining, the ageing of society means that an
      increase in absolute numbers is expected over coming years. Both cancers tend to
      present at an advanced stage, hence prognosis remains poor despite increasingly
      effective screening and treatment strategies. The development of gastric and
      oesophageal malignancies is influenced by myriad factors, not least geographical,
      racial and socioeconomic differences in addition to lifestyle choices. The
      multidimensional nature of these risk factors requires a holistic understanding
      of their net influence in the development of malignancy. This review explores the
      evidence base for established and putative risk factors in the development of
      gastric and oesophageal cancers. It is hoped that with a clear understanding of
      important risk factors, a multidisciplinary approach including effective primary
      prevention, regular screening of high-risk groups and continued research into the
      molecular biology of gastrointestinal carcinogenesis may facilitate a reduction
      in incidence rates, as well as early detection and optimal management of upper
      gastrointestinal malignancies.

PMID- 23129371
TI  - Endoscopic treatment for esophageal squamous cell carcinoma.

PMID- 23129372
TI  - Open or minimally invasive resection for oesophageal cancer?
AB  - Oesophagectomy is one of the most challenging surgical operations. Potential for
      morbidity and mortality is high. Minimally invasive techniques have been
      introduced in an attempt to reduce postoperative complications and recovery
      times. Debate continues over whether these techniques decrease morbidity and
      whether the quality of the oncological resection is compromised. Globally,
      minimally invasive oesophagectomy (MIO) has been shown to be feasible and safe,
      with outcomes similar to open oesophagectomy. There are no controlled trials
      comparing the outcomes of MIO with open techniques, just a few comparative
      studies and many single institution series from which assessments of the current
      role of MIO have been made. The reported improvements of MIO include reduced
      blood loss, shortened time in high dependency care and decreased length of
      hospital stay. In comparative studies there is no clear reduction in respiratory
      complications, although larger series suggest that MIO may have a benefit.
      Although MIO approaches report less lymph node retrieval compared with open
      extended lymphadenectomy, MIO cancer outcomes are comparable. MIO will be a major
      component of the future oesophageal surgeons' armamentarium, but should continue
      to be carefully assessed. Randomized trials comparing MIO versus open resection
      in oesophageal cancer are urgently needed: two phase III trials are recruiting,
      the TIME and the MIRO trials.

PMID- 23129373
TI  - Choosing the best treatment for esophageal cancer : criteria for selecting the
      best multimodal therapy.
AB  - The best multimodal therapy in esophageal cancer comprises neoadjuvant
      radiochemotherapy in patients with adenocarcinoma or squamous cell carcinoma
      whereas neoadjuvant chemotherapy is only appropriate for patients with
      adenocarcinoma. However, the 2-year survival benefit by this induction therapy
      compared to surgery alone is only 5-9 %. Targeted drugs seem to be promising in
      order to improve the response rate. The choice of the best multimodal therapy by
      response prediction seems only to be possible in patients during chemotherapy for
      adenocarcinoma, whereas during neoadjuvant radiochemotherapy a response
      prediction by FDG-PET is not possible. The principle item of multimodal therapy
      is still transthoracic en bloc esophagectomy which should be performed in high
      volume centers in order to guarantee stable and good results.

PMID- 23129374
TI  - Multimodal therapy of GEJ cancer: when is the definitive radiochemotherapy the
      treatment of choice?
AB  - Today, patients with localized gastroesophageal junction adenocarcinomas (AC)
      should be considered for combined modality therapy, at least when they have
      locally advanced (T3-T4 category) or lymph node positive tumors. But what about
      patients unable or unwilling to undergo surgical resection? Unlike esophageal
      squamous cell carcinoma (SCC), we have no randomized data to consider definitive
      radiochemotherapy without surgery as accepted treatment option in these patients.
      Retrospective results from an US surveillance epidemiology and end results (SEER)
      analysis state that the results of definitive or preoperative radio(chemo)therapy
      are equal or even improved for adenocarcinoma compared to SCC. Other
      retrospective data using the method of matched-pair analysis showed that median
      overall survival appears not different between AC and SCC after definitive
      radiochemotherapy. Nevertheless, since prospective randomized results are
      lacking, definitive radiochemotherapy cannot be considered as treatment standard
      in GEJ cancer, and therefore should be restricted to patients with increased
      operation risk.

PMID- 23129375
TI  - Radiotherapy of gastroesophageal junction cancer.
AB  - Adenocarcinomas of the gastroesophageal junction (GEJ) require multimodal
      treatment approaches to accomplish good local control and overall survival. While
      early T1/2 N0 tumors are treated with surgery alone, they are only found in a
      small subset of patients due to the lack of symptoms at this stage. Most of the
      tumors are detected in locally advanced stage where surgery alone results in
      disappointing outcome. Chemotherapy and/or chemoirradiation in the neoadjuvant
      setting are used to improve conditions for oncological surgery. They aim to
      achieve a downsizing with a pathological complete remission in the optimal case,
      improve R0 rates, and upfront treat microscopic metastatic tumor cells. The
      optimal neoadjuvant treatment approach-chemotherapy, chemoirradiation, or a
      multiphase approach of both-is yet unclear. Chemoirradiation can improve local
      control after incomplete surgery and is an important option for patients unfit
      for surgery. In addition, it enables symptom relief in a palliative setting,
      namely dysphagia, pain, or bleeding. While target volumes are very much
      standardized, new technologies as image-guided intensity-modulated radiotherapy
      (IG-IMRT) and particle therapy have the potential to improve the therapeutic
      window by minimizing toxicity. Challenges of the present and the future will be
      the combination of radiotherapy with other cytostatic drugs and modern targeted
      therapies. This should ideally be integrated into a multimodal setting that is
      able to identify risk groups according to predictive markers and tumor response,
      altogether leading to a personalized oncological approach.

PMID- 23129376
TI  - Optimizing neoadjuvant chemotherapy through the use of early response evaluation
      by positron emission tomography.
AB  - Metabolic imaging and early response assessment by positron emission tomography
      (PET) may guide treatment of localized esophageal cancers. The most consistent
      and validated results have been obtained during neoadjuvant treatment of
      adenocarcinoma of the esophago-gastric junction (AEG). It was demonstrated that
      18F-Fluorodeoxyglucoe (FDG)-PET is highly accurate for identifying non-responding
      tumors within 2 weeks after the initiation of neoadjuvant chemotherapy when a
      quantitative threshold for metabolic response is used. In consecutive phase II
      studies the metabolic activity, defined by the standardized uptake (SUV) of 18
      FDG before and during chemotherapy, was measured. Significant decreases of the
      SUV after only two weeks of induction chemotherapy were observed. A drop of >35 %
      2 weeks after the start of chemotherapy revealed as an accurate cut-off value to
      predict response after a 12-week course of preoperative chemotherapy. This cut
      off was recently confirmed in a US study, where investigators did follow-up PET
      not 14 days but 6 weeks after initiation of chemotherapy. It was further noticed
      that the metabolic response to induction chemotherapy revealed as an independent
      prognostic factor in locally advanced AEG. Therefore, PET could be used to tailor
      treatment according to the sensitivity of an individual tumor. This concept was
      realized in the MUNICON-1 and -2 trials. These trials prospectively confirmed
      that responders to induction chemotherapy can be identified by early metabolic
      imaging using FDG-PET. Continuing neoadjuvant chemotherapy in the responding
      population resulted in a favorable outcome. Moreover, MUNICON-1 showed that
      chemotherapy can be discontinued at an early stage in metabolic non-responders
      without compromising the patients' prognosis, but saving time and reducing side
      effects and costs. MUNICON-2 showed that the addition of neoadjuvant radiation
      therapy in metabolic nonresponders did not lead to an improvement of their poor
      prognosis, thus showing that early metabolic nonresponse indicates dismal tumor
      biology. Future studies need to validate the prognostic and predictive value of
      PET in multicenter settings and in conjunction with different neoadjuvant
      chemotherapy and chemo-immunotherapy regimens.

PMID- 23129377
TI  - Optimal surgery for gastric cancer: is more always better?
AB  - The extent of surgical resection for carcinoma of the stomach has been debated
      for many years. The aims of surgery are to obtain complete histopathological
      clearance of all possible sites of disease based on oncological principles. This
      has included radical resection of the primary site with combined organ resection
      as required and resection of associated lymph nodes. Detailed understanding of
      the natural history of gastric cancer has resulted in the Pichlmayr total
      gastrectomy "en principe" approach being super-ceded by a tailored approach
      according to tumour and patient characteristics. Careful tumour staging is
      fundamental to the selection of surgical intervention. Endoscopic therapy is
      recommended for well differentiated, mucosal cancers less than 2 cm in size as
      the risk of nodal disease is 0-3 %. Recently, these criteria have been extended
      to include some larger and ulcerated cancers. Although extended lymphadenectomy
      has formed the basis of radical surgery, Japanese experience has also confirmed
      that for early gastric cancer involving the submucosa limited nodal resection can
      achieve the same outcome as standardised D2 lymphadenectomy. The approach to
      locally advanced T2, T3 and some T4 cancers has been defined by the Japanese
      rules specifying proximal and distal margins as well as extent of lymph node
      resection. Translation of Japanese results to Western patients has not been
      straightforward. Two randomised controlled trials have shown limited or no
      benefit over conventional limited nodal dissection. However, these studies have
      not been without criticism and individual specialist practice in the West now
      preferentially includes D2 lymphadenectomy in suitable patients. Extending
      conventional D2 lymphadenectomy has been evaluated but the results are not
      conclusive. Japanese RCTs have not shown an advantage but in selected cases
      several groups have reported a benefit. Historically, radical gastric surgery in
      the West was associated with significant morbidity and mortality reflecting the
      comorbidity of the patient groups. Perioperative approaches have shown that
      outcome approaching that of radical surgery can be achieved with multimodal
      therapies for high-risk patient groups for whom radical surgery would be
      contraindicated. Surgery for gastric cancer needs to be determined by a
      multidisciplinary team to ensure appropriate procedure selection for an
      individual patient. This allows all relevant information to be considered and to
      provide the best chance for high-quality patient outcome.

PMID- 23129378
TI  - Can adjuvant chemoradiotherapy replace extended lymph node dissection in gastric
      cancer?
AB  - Surgical resection remains the essential part in the curative treatment of
      gastric cancer. However, with surgery only, long-term survival is poor (5-year
      survival <25 % in Europe). Randomized studies, which compared limited (D1) lymph
      node dissection with more extended (D2) resections in the Western world, failed
      to show a survival benefit for more extensive surgery. A substantial increase in
      survival was found with perioperative chemotherapy in the MAGIC study. In
      addition, the SWOG/Intergroup 0116 study showed that postoperative
      chemoradiotherapy (CRT) prolonged 5-year overall survival compared to surgery
      only. However, it has been argued that surgical undertreatment undermined
      survival in this trial. In a randomized Korean study, patients with advanced
      stage gastric cancer who received postoperative CRT had better outcome after a D2
      dissection. At our institute phase I-II studies with adjuvant cisplatin and
      capecitabine-based CRT have been performed in over 120 patients with resected
      gastric cancer. Retrospective comparison of patients treated in these studies
      with those that had surgery only in the D1D2 study, demonstrated that
      postoperative CRT was associated with better outcome, especially after D1 or a R1
      resection. For daily practice, it remains unclear whether patients after optimal
      (D2) gastric surgery will benefit from postoperative CRT. This is currently being
      tested in prospective randomized phase III trials (CRITICS; TOPGEAR).

PMID- 23129379
TI  - Predicting the response to chemotherapy in gastric adenocarcinoma: who benefits
      from neoadjuvant chemotherapy?
AB  - Despite a decline in the overall incidence, gastric adenocarcinoma remains the
      second most common cause of cancer death worldwide and thus a significant global
      health problem. Even in early-stage locoregional confined disease the 5-year
      survival rarely exceeds 25-35 %. Randomized trials have demonstrated a benefit
      from neoadjuvant and perioperative chemotherapy. However the optimal approach in
      individual patients is not clear and remains controversial. A consistent finding
      is that patients who have a histopathological response to neoadjuvant therapy are
      more likely to receive a survival benefit. These clinical data provide a strong
      argument for the urgent development of methods to predict histopathological
      response to neoadjuvant therapies for gastric adenocarcinomas. Published data
      demonstrate that clinico-pathological features (tumour histology and location),
      imaging through metabolic response by FDG-PET and tissue/molecular biomarkers may
      all have a predictive value for neoadjuvant therapies. However it is still
      uncertain from published data whether or not they will be useful for clinical
      decision making in individual patients. Existing candidate biomarkers need to be
      properly qualified and validated and novel biomarkers are required and an optimal
      approach should involve the combination and integration of clinical, imaging,
      pathological and molecular biomarkers.

PMID- 23129380
TI  - Prediction of response and prognosis by a score including only pretherapeutic
      parameters in 410 neoadjuvant treated gastric cancer patients.
AB  - INTRODUCTION: Response to neoadjuvant chemotherapy (NAC) is an independent
      prognostic factor in locally advanced gastric cancer. However, no prospectively
      tested pretherapeutic parameters predicting response and/or survival in gastric
      cancer are available in clinical routine. PATIENTS AND METHODS: We evaluated the
      prognostic significance of various clinicopathologic parameters in 410 patients
      who were treated with NAC followed by gastrectomy. Clinical and histopathological
      response evaluation was performed using standardized criteria. A prognostic score
      was created on the basis of the variables identified in the multivariate
      analysis. RESULTS: Multivariate analysis identified three pretherapeutic
      parameters as positive predictive factors for response and prognosis: tumor
      localization in the middle third of the stomach (p = 0.001), well differentiated
      tumors (p = 0.001) and intestinal tumor type according to Lauren's classification
      (p = 0.03). From the obtained data a prognostic index was constructed, dividing
      the patients into three risk groups: low (n = 73), intermediate (n = 274), and
      poor (n = 63). The three groups had significantly different clinical (p = 0.007)
      and histopathological response rates (p = 0.001) and survival times, with a
      median survival time that was not reached in the low-risk group, 39.2 months in
      the intermediate-risk group and 20.5 months in the poor-risk group. The
      corresponding 5-year survival rates were 65.3, 41.2, and 21.2 % (p < 0.001),
      respectively. CONCLUSION: A simple scoring system based on three
      clinicopathologic parameters, accurately predicts response and prognosis in
      neoadjuvant treated gastric cancer. This system provides additional useful
      information that could be applied to select gastric cancer patients
      pretherapeutically for different treatment approaches. Prospective testing of the
      score in an independent patient cohort is warranted.

PMID- 23129381
TI  - Adjuvant chemotherapy: an option for Asian patients only?
AB  - Survival rates following curative resection for gastric cancer are higher in East
      Asia than in Europe and the US. The aggressive surgical approach adopted in East
      Asia may explain these observations. In Japan and Korea, gastrectomy with
      extended lymphadenectomy (D2 gastrectomy) has been standard of care for many
      years, whereas gastrectomy with lymphadenectomy of the perigastric lymph nodes
      (D1 surgery) has been favored in Europe and the US until recently. D2 surgery is
      now recommended globally based on the 15-year findings from the large Dutch D1D2
      study, which showed a reduction in cancer-related deaths with D2 versus D1
      surgery. Improved outcomes are now being reported in the US and Europe as D2
      surgery becomes more widely used. In addition to surgery, systemic therapy is
      also required to control recurrences, although the preferred regimen differs by
      region. Given that some of the studies on which these preferences are based
      predate the widespread acceptance of D2 surgery, the optimal regimen should be
      considered carefully. Recent studies from East Asia support the use of adjuvant
      chemotherapy after D2 surgery. Adjuvant chemotherapy should also be considered a
      valid approach in other regions now that the benefits of D2 surgery have been
      demonstrated unequivocally.

PMID- 23129382
TI  - Selecting the best treatment for an individual patient.
AB  - Several factors concur in determining outcome for locally advanced gastric cancer
      patients. Shockingly, geographic origin of the patient seems to play a major
      role. In Eastern countries, the high level of surgery that can be expected grants
      a high percentage of success in a strategy that employs surgery as immediate
      treatment followed by adjuvant chemotherapy, mainly based on oral
      fluoropyrimidines (S-1 or Capecitabine), with satisfactory results. In Western
      countries, the expertise of the surgeon maintains its role as predictor of high
      likelihood of cure. Indeed, patients treated with standard D2 lymph node
      dissection have a significantly better survival than those who do not obtain the
      same kind of treatment. For patients who underwent a suboptimal resection (less
      than a D1) the classical indication is for a combined adjuvant chemoradiotherapy.
      In patients who obtain a good surgical outcome, the benefit of the addition of
      adjuvant chemotherapy is still debatable: the gain in survival seems to be small
      (around 8 % at 5 years) and with noticeable toxicities (usually with dismal
      compliance for patients treated). On this basis, neoadjuvant treatment is a
      promising option even if there is a general lack of conclusive data regarding
      which is the best regimen to use. Even with the limitation of a small number of
      studies (with difficulties in enrollment), neoadjuvant chemotherapy is usually
      feasible, allows for a greater chance of receiving chemotherapy at all, and opens
      the possibility of a downstaging and downsizing of the tumor, allowing an easier
      surgery. Regarding this strategy preliminary results have also been presented
      about the addition of monoclonal antibodies. For example, in the TOGA trial, a
      significant benefit in terms of overall survival, response rate, and progression
      free survival was observed also for patients with locally advanced gastric cancer
      and not just for the metastatic ones. In the AVAGAST trial also, the addition of
      Bevacizumab failed to determine a significant improvement in the primary outcome,
      overall survival, for patients treated with the combination, but in the subgroup
      analysis, patients with locally advanced gastric cancer had a significantly
      better overall survival and response rate. This data was the basis for the newest
      neoadjuvant trial, of Cunningham et al., the MAGIC2 trial, with the peri
      operative use of ECX+Bevacizumab. Finally, an increasing interest in the use of
      hyperthermic intraperitoneal chemotherapy in other types of solid tumors
      (including those of the gastrointestinal tract such as colon cancer) has led to
      evaluate this treatment modality in gastric cancer patients with peritoneal
      involvement. It should be noted that it is still to be considered an experimental
      approach, even though it would be intriguing to evaluate if a particular subset
      of patients, those who are more likely to develop peritoneal metastasis, may
      benefit from this technique in the adjuvant setting. It should be considered that
      other than histologic subtype (diffuse vs intestinal) there seems to be a series
      of polymorphisms of genes usually involved in cell interaction and migration that
      can explain a different metastatic pattern in resected patients. Further research
      on these determinants of metastatic spread could be used to select those patients
      who may benefit from HIPEC and those who may benefit from standard adjuvant or
      that gain no benefit at all.

PMID- 23129383
TI  - Nocturnal mouthpiece ventilation and medical hypnosis to treat severe obstructive
      sleep apnea in a child with cherubism.
AB  - A 4-year old boy presented severe obstructive sleep apnoea due to complete nasal
      obstruction secondary to cherubism. Because of anticipatory anxiety due to
      numerous surgical interventions, medical hypnosis was proposed to facilitate non
      invasive continuous positive pressure ventilation (CPAP) acceptance. CPAP by
      means of an oral interface was completely accepted after three hypnosis sessions
      and resulted in the correction of his obstructive sleep apnea (OSA) syndrome.
      This report highlights the benefit of medical hypnosis in facilitating CPAP
      acceptance as well as the efficacy of mouthpiece ventilation in a severe form of
      cherubism with complete nasal obstruction.

PMID- 23129384
TI  - Genetic and molecular characterization of the human osteosarcoma 3AB-OS cancer
      stem cell line: a possible model for studying osteosarcoma origin and stemness.
AB  - Finding new treatments targeting cancer stem cells (CSCs) within a tumor seems to
      be critical to halt cancer and improve patient survival. Osteosarcoma is an
      aggressive tumor affecting adolescents, for which there is no second-line
      chemotherapy. Uncovering new molecular mechanisms underlying the development of
      osteosarcoma and origin of CSCs is crucial to identify new possible therapeutic
      strategies. Here, we aimed to characterize genetically and molecularly the human
      osteosarcoma 3AB-OS CSC line, previously selected from MG63 cells and which
      proved to have both in vitro and in vivo features of CSCs. Classic cytogenetic
      studies demonstrated that 3AB-OS cells have hypertriploid karyotype with 71-82
      chromosomes. By comparing 3AB-OS CSCs to the parental cells, array CGH,
      Affymetrix microarray, and TaqMan(r) Human MicroRNA array analyses identified 49
      copy number variations (CNV), 3,512 dysregulated genes and 189 differentially
      expressed miRNAs. Some of the chromosomal abnormalities and mRNA/miRNA expression
      profiles appeared to be congruent with those reported in human osteosarcomas.
      Bioinformatic analyses selected 196 genes and 46 anticorrelated miRNAs involved
      in carcinogenesis and stemness. For the first time, a predictive network is also
      described for two miRNA family (let-7/98 and miR-29a,b,c) and their
      anticorrelated mRNAs (MSTN, CCND2, Lin28B, MEST, HMGA2, and GHR), which may
      represent new biomarkers for osteosarcoma and may pave the way for the
      identification of new potential therapeutic targets.

PMID- 23129385
TI  - HOXB13 mutations in a population-based, case-control study of prostate cancer.
AB  - BACKGROUND: Prostate cancer (PC) is the most frequently diagnosed non-skin
      malignancy in men in the Western world, yet few disease-associated mutations have
      been found. Recently, a low frequency recurring mutation in the HOXB13 gene was
      reported among both hereditary PC families and men from the general population.
      MATERIALS AND METHODS: We determined the distribution and frequency of the G84E
      HOXB13 variant in 1,310 incipient PC cases and 1,259 age-mated controls from a
      population-based, case-control study of PC. RESULTS: The G84E mutation was more
      frequent in cases than controls (1.3% vs. 0.4%, respectively), and men with the
      HOXB13 G84E variant had a 3.3-fold higher relative risk of PC compared with
      noncarriers (95% CI, 1.21-8.96). There was a stronger association between the
      G84E variant and PC among men with no first-degree relative with PC (OR, 4.04;
      95% CI, 1.12-14.51) compared to men with a family history of PC (OR, 1.49; 95%
      CI, 0.30-7.50; P = 0.36 for interaction). We observed some evidence of higher
      risk estimates associated with the variant for men with higher versus lower
      Gleason score (OR, 4.13; 95% CI, 1.38-12.38 vs. OR, 2.71; 95% CI, 0.88-8.30), and
      advanced versus local stage (OR, 4.47; 95% CI, 1.28-15.57 vs. OR, 2.98; 95% CI,
      1.04-8.49), however these differences were not statistically different.
      CONCLUSIONS: These results confirm the association of a rare HOXB13 mutation with
      PC in the general population and suggest that this variant may be associated with
      features of more aggressive disease.

PMID- 23129386
TI  - National Cancer Institute to merge programs: combined program to focus on cancer
      care delivery research in the community setting.

PMID- 23129387
TI  - Surgery no better than observation for localized prostate cancer.

PMID- 23129388
TI  - Lack of insurance linked to advanced stage cervical cancer.

PMID- 23129389
TI  - [Use of medical inpatient services by heavy users: a case of hypochondriasis].
AB  - Hypochondriasis is defined by ICD-10 and DSM-IV through the persistent
      preoccupation with the possibility of having one or more serious and progressive
      physical disorders. Patients suffering from hypochondriasis can be responsible
      for a high utilization of mental health system services. Data have shown that
      "Heavy User" require a disproportionate part of inpatient admissions and mental
      health budget costs. We assume that a psychotherapeutic approach, targeting a
      cognitive behavioral model in combination with neuropsychopharmacological
      treatment is useful. In our case report we present the "Heavy Using-Phenomenon"
      based on a patient hospitalized predominantly in neurological inpatient care
      facilities. From a medical point of view we want to point out to possible
      treatment errors, on the other hand we want to make aware of financial
      socioeconomic factors leading to a massive burden on the global mental health
      budget.

PMID- 23129390
TI  - Identification of genetic associations of SP110/MYBBP1A/RELA with pulmonary
      tuberculosis in the Chinese Han population.
AB  - Genetic factors play important roles in the development of tuberculosis (TB).
      SP110 is a promising candidate target for controlling TB infections. However,
      several studies associating SP110 single nucleotide polymorphisms (SNPs) with TB
      have yielded conflicting results. This may be partly resolved by studying other
      genes associated with SP110, such as MYBBP1A and RELA. Here, we genotyped 6 SP110
      SNPs, 8 MYBBP1A SNPs and 5 RELA SNPs in 702 Chinese pulmonary TB patients and 425
      healthy subjects using MassARRAY and SNaPshot methods. Using SNP-based analysis
      with Bonferroni correction, rs3809849 in MYBBP1A [Pcorrected (cor) = 0.0038] and
      rs9061 in SP110 (Pcor = 0.019) were found to be significantly associated with TB.
      Furthermore, meta-analysis of rs9061 in East Asian populations showed that the
      rs9061 T allele conferred significant risk for TB [P = 0.002, pooled odds ratio
      (OR), 1.24, 95% confidence interval (CI) = 1.08-1.43]. The MYBBP1A GTCTTGGG
      haplotype and haplotypes CGACCG/TGATTG within SP110 were found to be markedly and
      significantly associated with TB (P = 2.00E-06, 5.00E-6 and 2.59E-4,
      respectively). Gene-based analysis also demonstrated that SP110 and MYBBP1A were
      each associated with TB (Pcor = 0.011 and 0.035, respectively). The logistic
      regression analysis results supported interactions between SP110 and MYBBP1A,
      indicating that subjects carrying a GC/CC genotype in MYBBP1A and CC genotype in
      SP110 possessed the high risk of developing TB (P = 1.74E-12). Our study suggests
      that a combination of SP110 and MYBBP1A gene polymorphisms may serve as a novel
      marker for identifying the risk of developing TB in the Chinese Han population.

PMID- 23129393
TI  - Stability of cluster solutions in a cooperative consumer chain model.
AB  - We study a cooperative consumer chain model which consists of one producer and
      two consumers. It is an extension of the Schnakenberg model suggested in Gierer
      and Meinhardt [Kybernetik (Berlin), 12:30-39, 1972] and Schnakenberg (J Theor
      Biol, 81:389-400, 1979) for which there is only one producer and one consumer. In
      this consumer chain model there is a middle component which plays a hybrid role:
      it acts both as consumer and as producer. It is assumed that the producer
      diffuses much faster than the first consumer and the first consumer much faster
      than the second consumer. The system also serves as a model for a sequence of
      irreversible autocatalytic reactions in a container which is in contact with a
      well-stirred reservoir. In the small diffusion limit we construct cluster
      solutions in an interval which have the following properties: The spatial profile
      of the third component is a spike. The profile for the middle component is that
      of two partial spikes connected by a thin transition layer. The first component
      in leading order is given by a Green's function. In this profile multiple scales
      are involved: The spikes for the middle component are on the small scale, the
      spike for the third on the very small scale, the width of the transition layer
      for the middle component is between the small and the very small scale. The first
      component acts on the large scale. To the best of our knowledge, this type of
      spiky pattern has never before been studied rigorously. It is shown that, if the
      feedrates are small enough, there exist two such patterns which differ by their
      amplitudes.We also study the stability properties of these cluster solutions. We
      use a rigorous analysis to investigate the linearized operator around cluster
      solutions which is based on nonlocal eigenvalue problems and rigorous asymptotic
      analysis. The following result is established: If the time-relaxation constants
      are small enough, one cluster solution is stable and the other one is unstable.
      The instability arises through large eigenvalues of order O1. Further, there are
      small eigenvalues of order o1 which do not cause any instabilities. Our approach
      requires some new ideas: (i) The analysis of the large eigenvalues of order O1
      leads to a novel system of nonlocal eigenvalue problems with inhomogeneous Robin
      boundary conditions whose stability properties have been investigated rigorously.
      (ii) The analysis of the small eigenvalues of order o1 needs a careful study of
      the interaction of two small length scales and is based on a suitable inner/outer
      expansion with rigorous error analysis. It is found that the order of these small
      eigenvalues is given by the smallest diffusion constant epsilon2(2).

PMID- 23129392
TI  - Mathematical modeling of collagen turnover in biological tissue.
AB  - We present a theoretical and computational model for collagen turnover in soft
      biological tissues. Driven by alterations in the mechanical environment, collagen
      fiber bundles may undergo important chronic changes, characterized primarily by
      alterations in collagen synthesis and degradation rates. In particular,
      hypertension triggers an increase in tropocollagen synthesis and a decrease in
      collagen degradation, which lead to the well-documented overall increase in
      collagen content. These changes are the result of a cascade of events, initiated
      mainly by the endothelial and smooth muscle cells. Here, we represent these
      events collectively in terms of two internal variables, the concentration of
      growth factor TGF-beta and tissue inhibitors of metalloproteinases TIMP. The
      upregulation of TGF-beta increases the collagen density. The upregulation of TIMP
      also increases the collagen density through decreasing matrix metalloproteinase
      MMP. We establish a mathematical theory for mechanically-induced collagen
      turnover and introduce a computational algorithm for its robust and efficient
      solution. We demonstrate that our model can accurately predict the experimentally
      observed collagen increase in response to hypertension reported in literature.
      Ultimately, the model can serve as a valuable tool to predict the chronic
      adaptation of collagen content to restore the homeostatic equilibrium state in
      vessels with arbitrary micro-structure and geometry.

PMID- 23129394
TI  - Group defence and the predator's functional response.
AB  - We derive from first principles the functional response of the predator and the
      reproduction rate of the prey in the case that the prey form groups as a defence
      against the predator and the latter captures only single prey. We also give some
      examples of the resulting predator-prey population dynamics.

PMID- 23129395
TI  - Molecular ionics in supramolecular assemblies with channel structures containing
      lithium ions.
AB  - A novel trilithium compound,
      Li(3)[B(C(6)H(4)O(2)){O(CH(2)CH(2)O)(3)CH(3)}(2)][N(SO(2)CF(3))(2)](2) (1-2.0),
      with solid-state ionic conductivity was synthesized. The crystal structure of 1
      2.0 consists of the one-dimensional ionic conduction paths. The paths were
      afforded as a result of the self-assembled stacking of the component molecules of
      1-2.0 with channel structures containing lithium ions. In this supramolecule, one
      lithium ion holds the component molecules in specific positions to construct a
      supramolecular structure with thermally stable ionic conduction paths and the
      others behave as carrier ions exhibiting selective lithium-ion conductivity.
      Owing to the existence of both roles for the lithium ions, this electrolyte shows
      selective lithium-ion conductivity.

PMID- 23129391
TI  - Effects of cannabis on neurocognitive functioning: recent advances,
      neurodevelopmental influences, and sex differences.
AB  - Decades of research have examined the effects of cannabis on neurocognition.
      Recent advances in this field provide us with a better understanding of how
      cannabis use influences neurocognition both acutely (during intoxication) and non
      acutely (after acute effects subside). Evidence of problems with episodic memory
      is one of the most consistent findings reported; however, several other
      neurocognitive domains appear to be adversely affected by cannabis use under
      various conditions. There is significant variability in findings across studies,
      thus a discussion of potential moderators is increasingly relevant. The purpose
      of this review was to 1) provide an update on research of cannabis' acute and non
      acute effects on neurocognition, with a focus on findings since 2007 and 2)
      suggest and discuss how neurodevelopmental issues and sex differences may
      influence cannabis effects on neurocognition. Finally we discuss how future
      investigations may lead to better understanding of the complex interplay among
      cannabis, stages of neurodevelopment, and sex on neurocognitive functioning.

PMID- 23129396
TI  - Electronic and optical vibrational spectroscopy of molecular transport junctions
      created by on-wire lithography.

PMID- 23129397
TI  - Pelvic floor muscle training program increases muscular contractility during
      first pregnancy and postpartum: electromyographic study.
AB  - AIMS: The aim of this study was to evaluate the effect of a training program over
      both pelvic floor muscles contractility and urinary symptoms in primigravid
      pregnant and postpartum primiparous women. PATIENTS AND METHODS: A clinical,
      prospective and blinded trial was conducted with 33 women divided into three
      groups: (G1) 13 primigravid pregnant women; (G2) 10 postpartum primiparous women
      (49.3 +/- 5.84 days), after vaginal delivery with right mediolateral episiotomy;
      (G3) 10 postpartum primiparous women (46.3 +/- 3.6 days), after cesarean section
      delivery. The evaluation was carried out using digital palpation (Modified Oxford
      Grading Scale), pelvic floor electromyography and, for the investigation of
      urinary symptoms, validated questionnaires (International Consultation on
      Incontinence Questionnaire-short form-ICIQ-UI SF and International Consultation
      on Incontinence Questionnaire Overactive Bladder-ICIQ-OAB). The protocol
      consisted of 10 individual sessions carried out by the physiotherapist through
      home visits, three times a week, with 60 min duration each. The statistical
      analysis was performed using ANOVA and Spearman's correlation coefficient.
      RESULTS: The pelvic floor muscle contractility increased after the training
      program (P = 0.0001) for all groups. Decreases in the scores of both ICIQ-UI SF
      (P = 0.009) and ICIQ-OAB (P = 0.0003) were also observed after training.
      CONCLUSION: Pelvic floor muscle training is an effective means for the increase
      in its own contractility in both primigravid pregnant and primiparous postpartum
      women, accompanied with a concomitant decrease in urinary symptoms.

PMID- 23129398
TI  - The impact of bronchopulmonary dysplasia on caregiver health related quality of
      life during the first 2 years of life.
AB  - OBJECTIVES: Preterm children with bronchopulmonary dysplasia (BPD) frequently
      require complex home medical regimens and re-hospitalization during the first 2
      years of life. The burden of caring for these medically complex children may
      negatively affect caregiver health related quality of life (HRQoL). The
      objectives of this study were to measure caregiver HRQoL of children with BPD and
      to identify factors that impact caregiver HRQoL during the first 2 years of life.
      METHODS: Children (n = 186) were recruited from the Johns Hopkins BPD Outpatient
      Clinic between January 2008 and July 2011. Caregiver HRQoL was measured using The
      PedsQL(TM) Family Impact Module. Respiratory symptoms and morbidities were
      assessed using questionnaires. RESULTS: Among caregivers of BPD children,
      significant improvement in physical, worry, and daily domains improved
      longitudinally as children aged. An association was found between lower total
      HRQoL scores and caregivers of BPD children who reported more respiratory
      symptoms and acute care usage. No difference in total HRQoL scores was found
      between caregivers of BPD children requiring respiratory/enteral support and
      caregivers of children who did not. Caregiver income and educational level did
      not predict total HRQoL score, but Non-White race and public insurance was
      associated with a higher total HRQoL score at the first outpatient visit.
      CONCLUSION: An association was found between lower HRQoL scores and caregivers of
      BPD children with frequent respiratory symptoms and acute care usage. Screening
      for low HRQoL in caregivers of BPD children with frequent respiratory illnesses
      should be considered to identify those who may benefit from additional support
      and intervention.

PMID- 23129399
TI  - The impairment of insulin signaling in Alzheimer's disease.
AB  - Alterations of the insulin signaling cascade underlie cognitive decline and the
      development of several neurodegenerative diseases. In recent years, a great
      interest has been put in studying the interaction between diabetes and
      Alzheimer's disease (AD). In fact, evidence shows that both diseases present
      several biochemical similarities including defects in the insulin signaling
      pathway. Here, we give an overview of the main functions of insulin in the
      central nervous system. The impact of insulin signaling impairment in brain aging
      and AD is also discussed. Finally, we present evidence supporting the notion that
      insulin is a link between diabetes and AD.

PMID- 23129400
TI  - Evidence for pollen limitation of a native plant in invaded communities.
AB  - Animal-pollinated invasive species have frequently been demonstrated to
      outcompete native species for pollinator attention, which can have detrimental
      effects on the reproductive success and population dynamics of native species.
      Many animal-pollinated invasive species exhibit showy flowers and provide
      substantial rewards, allowing them to act as pollinator 'magnets', which, at a
      large scale, can attract more pollinators to an area, but, at a smaller scale,
      may reduce compatible pollen flow to local native species, possibly explaining
      why most studies detect competition. By performing pollen limitation experiments
      of populations in both invaded and uninvaded sites, we demonstrate that the
      invasive plant Lythrum salicaria appears to facilitate, rather than hinder, the
      reproductive success of native confamilial Decodon verticillatus, even at a small
      scale, in a wetland habitat in southeastern Ontario. We found no evidence for a
      magnet species effect on pollinator attraction to invaded sites. Germination
      experiments confirmed that seeds from invaded sites had similar germination rates
      to those from uninvaded sites, making it unlikely that a difference in inbreeding
      was masking competitive effects. We describe several explanations for our
      findings. Notably, there were no differences in seed set among populations at
      invaded and uninvaded sites. Our results underscore the inherent complexity of
      studying the ecological impacts of invasive species on natives.

PMID- 23129402
TI  - Intraoperative continuous hemodiafiltration with selective venous drainage of
      ischemic limbs.
AB  - We report two cases of acute limb ischemia with threatened myonephropathic
      metabolic syndrome (MNMS) in which continuous hemodiafiltration (CHDF) was
      started before revascularization with selective drainage from the clamped femoral
      vein of ischemic limb and return of processed blood into the contralateral
      femoral vein. It was aimed to optimise the removal of metabolites which were
      produced by myolysis following reperfusion as well as to minimize the deviation
      of metabolites into the systemic circulation. Both cases had uneventful
      postoperative course without MNMS and the limbs were salvaged.

PMID- 23129401
TI  - Are cyanobacterial blooms trophic dead ends?
AB  - Cyanobacterial blooms induce significant costs that are expected to increase in
      the near future. Cyanobacterial resistance to zooplankton grazing is one factor
      thought to promote bloom events. Yet, numerous studies on zooplankton ability to
      graze upon cyanobacteria have been producing contradictory results and such a
      puzzle might arise from the lack of direct observations in situ. Our objective
      was to track, using fatty acid (FA) and fatty acid stable isotope analyses (FA
      SIA), the fate of cyanobacterial organic matter in the food web of a lake
      subjected to summer blooms of Planktothrix rubescens. A metalimnetic bloom of P.
      rubescens occurred in Lake Bourget (France) during the study period (May-November
      2009). The bloom was especially rich in alpha-linolenic acid, 18:3(n-3), but none
      of the considered zooplankton taxa exhibited spiking content in this particular
      FA. FA-SIA revealed, however, that over a quarter of 18:3(n-3) in small
      zooplankton (<500 MUm) was provided by P. rubescens while large cladocerans (>500
      MUm) did not benefit from it. P. rubescens 18:3(n-3) could be tracked up to perch
      (Perca fluviatilis) young of the year (YOY) to which it contributed to ~15 % of
      total 18:3(n-3). Although transferred with a much lower efficiency than micro
      algal organic matter, the P. rubescens bloom supported a significant share of the
      pelagic secondary production and did not constitute, sensu stricto, a 'trophic
      dead end'. The cyanobacterial bloom also provided perch YOY with components of
      high nutritional values at a season when these are critical for their
      recruitment. This cyanobacterial bloom might thus be regarded as a significant
      dietary bonus for juvenile fish.

PMID- 23129403
TI  - Diastereodivergent synthesis of trisubstituted alkenes through protodeboronation
      of allylic boronic esters: application to the synthesis of the Californian red
      scale beetle pheromone.
AB  - E-allylic boronic esters undergo a highly diastereoselective protodeboronation
      with TBAF?3 H(2)O to give Z-trisubstituted alkenes. The selectivity can be
      switched to give predominantly the E-alkene instead by using KHF(2)/TsOH (see
      scheme). The utility of the methodology has been illustrated in a short synthesis
      of a component of the sex pheromone of the Californian red scale beetle.

PMID- 23129404
TI  - Leptin modulates dose-dependently the metabolic and cytolytic activities of NK-92
      cells.
AB  - Leptin, a hormone-cytokine produced primarily in the adipose tissue, has
      pleiotropic effects on many biological systems and in several cell types,
      including immune cells. Hyperleptinemia is associated with immune dysfunction and
      carcinogenesis. Natural killer (NK) cells are critical mediators of anti-tumor
      immunity, and leptin receptor deficiency in mice leads to impaired NK function.
      It was thus decided to explore the in vitro effects of leptin on human NK cell
      function. NK-92 cells were cultured during 48 h with different leptin
      concentrations [absence, 10 (physiological), 100 (obesity), or 200 ng/ml
      (pharmacology)]. Their metabolic activity was assessed using the resazurin test.
      NK-92 cell cytotoxicity and intracellular IFN-gamma production were analyzed by
      flow cytometry. NK-92 cell mRNA and protein expression levels of cytotoxic
      effectors were determined by RT-qPCR and Western blot. In our conditions, leptin
      exerted a dose-dependent stimulatory effect on NK-92 cell metabolic activity. In
      addition, high leptin concentrations enhanced NK-92 cell cytotoxicity against
      K562-EGFP and MDA-MB-231-EGFP target cells and inversely reduced cytotoxicity
      against the MCF-7-EGFP target. At 100 ng/ml, leptin up-regulated both NK cell
      granzyme B and TRAIL protein expressions and concomitantly down-regulated
      perforin expression without affecting Fas-L expression. In response to
      PMA/ionomycin stimulation, the proportion of IFN-gamma expressing NK-92 cells
      increased with 100 and 200 ng/ml of leptin. In conclusion, leptin concentration,
      at obesity level, variably increased NK-92 cell metabolic activity and modulated
      NK cell cytotoxicity according to the target cells. The underlying mechanisms are
      partly due to an up-regulation of TRAIL and IFN-gamma expression and a down
      regulation of perforin.

PMID- 23129405
TI  - A new signal-on photoelectrochemical biosensor based on a graphene/quantum-dot
      nanocomposite amplified by the dual-quenched effect of bipyridinium relay and
      AuNPs.
AB  - A new photoelectrochemical (PEC) biosensor was developed by using carboxyl
      functionalized graphene and CdSe nanoparticles. This sensitive interface was then
      successfully applied to detection of thrombin based on the dual-quenched effect
      of PEC nanoparticle, which relied on the electron transfer of a bipyridinium
      relay and energy transfer of AuNPs. After recognition with an aptamer, the PEC
      nanoparticle was removed and a signal-on PEC biosensor was obtained. Moreover,
      the bio-barcode technique used in the preparation of PEC nanoparticle could avoid
      cross-reaction and enhances the sensitivity. Taking advantages of the various
      methods mentioned above, the sensitivity could be easily enhanced. In addition,
      in this work we also investigated graphene that was modified with different
      functional groups and AuNPs of different particle sizes. Under optimal
      conditions, a detection limit of 5.9*10(-15)  M was achieved. With its
      simplicity, selectivity, and sensitivity, this strategy shows great promise for
      the fabrication of highly efficient PEC biosensors.

PMID- 23129406
TI  - How does biology emerge from chemistry?

PMID- 23129407
TI  - Strain-specific induction of experimental autoimmune prostatitis (EAP) in mice.
AB  - BACKGROUND: Prostatitis, a clinical syndrome characterized by pelvic pain and
      inflammation, is common in adult males. Although several induced and spontaneous
      murine models of prostatitis have been explored, the role of genetic background
      on induction has not been well-defined. METHODS: Using a standard methodology for
      the induction of experimental autoimmune prostatitis (EAP), we investigated both
      acute and chronic inflammation on several murine genetic backgrounds. RESULTS: In
      our colony, nonobese diabetic (NOD) mice evinced spontaneous prostatitis that was
      not augmented by immunization with rat prostate extract (RPE). In contrast, the
      standard laboratory strain Balb/c developed chronic inflammation in response to
      RPE immunization. Development of EAP in other strains was variable. CONCLUSIONS:
      These data suggest that Balb/c mice injected with RPE may provide a useful model
      for chronic prostatic inflammation.

PMID- 23129408
TI  - Vertical ozone characteristics in urban boundary layer in Beijing.
AB  - Vertical ozone and meteorological parameters were measured by tethered balloon in
      the boundary layer in the summer of 2009 in Beijing, China. A total of 77
      tethersonde soundings were taken during the 27-day campaign. The surface ozone
      concentrations measured by ozonesondes and TEI 49C showed good agreement, albeit
      with temporal difference between the two instruments. Two case studies of
      nocturnal secondary ozone maxima are discussed in detail. The development of the
      low-level jet played a critical role leading to the observed ozone peak
      concentrations in nocturnal boundary layer (NBL). The maximum of surface ozone
      was 161.7 ppbv during the campaign, which could be attributed to abundant
      precursors storage near surface layer at nighttime. Vertical distribution of
      ozone was also measured utilizing conventional continuous analyzers on 325-m
      meteorological observation tower. The results showed the NBL height was between
      47 and 280 m, which were consistent with the balloon data. Southerly air flow
      could bring ozone-rich air to Beijing, and the ozone concentrations exceeded the
      China's hourly ozone standard (approximately 100 ppb) above 600 m for more than
      12 h.

PMID- 23129409
TI  - Estimation of phosphorus flux in rivers during flooding.
AB  - Reservoirs in Taiwan are inundated with nutrients that result in algal growth,
      and thus also reservoir eutrophication. Controlling the phosphorus load has
      always been the most crucial issue for maintaining reservoir water quality.
      Numerous agricultural activities, especially the production of tea in riparian
      areas, are conducted in watersheds in Taiwan. Nutrients from such activities,
      including phosphorus, are typically flushed into rivers during flooding, when
      over 90% of the yearly total amount of phosphorous enters reservoirs. Excessive
      or enhanced soil erosion from rainstorms can dramatically increase the river
      sediment load and the amount of particulate phosphorus flushed into rivers. When
      flow rates are high, particulate phosphorus is the dominant form of phosphorus,
      but sediment and discharge measurements are difficult during flooding, which
      makes estimating phosphorus flux in rivers difficult. This study determines total
      amounts of phosphorus transport by measuring flood discharge and phosphorous
      levels during flooding. Changes in particulate phosphorus, dissolved phosphorus,
      and their adsorption behavior during a 24-h period are analyzed owing to the fact
      that the time for particulate phosphorus adsorption and desorption approaching
      equilibrium is about 16 h. Erosion of the reservoir watershed was caused by
      adsorption and desorption of suspended solids in the river, a process which can
      be summarily described using the Lagmuir isotherm. A method for estimating the
      phosphorus flux in the Daiyujay Creek during Typhoon Bilis in 2006 is presented
      in this study. Both sediment and phosphorus are affected by the drastic discharge
      during flooding. Water quality data were collected during two flood events, flood
      in June 9, 2006 and Typhoon Bilis, to show the concentrations of suspended solids
      and total phosphorus during floods are much higher than normal stages. Therefore,
      the drastic changes of total phosphorus, particulate phosphorus, and dissolved
      phosphorus in rivers during flooding should be monitored to evaluate the loading
      of phosphorus more precisely. The results show that monitoring and controlling
      phosphorus transport during flooding can help prevent the eutrophication of a
      reservoir.

PMID- 23129410
TI  - Surfactant-concentration-dependent shape evolution of Au-Pd alloy nanocrystals
      from rhombic dodecahedron to trisoctahedron and hexoctahedron.
AB  - The surface structure-controlled synthesis of noble metal nanocrystals (NCs)
      bounded by high-index facets has become a hot research topic due to their
      potential to significantly improve catalytic performance. This study reports the
      preparation of monodisperse Au-Pd alloy NCs with systematic shape evolution from
      rhombic dodecahedral (RD) to trisoctahedral (TOH), and hexoctahedral (HOH)
      structures by varying the concentration of surfactant in the surfactant-mediated
      synthesis. The as-prepared three kinds of alloy NCs possess almost the same size
      and composition as each other. It is suggested that the surfactant containing
      long-chain octadecyltrimethyl ammonium (OTA(+)) ions plays a key role in the
      formation of high index facets, and the crystal growth kinetics may also have an
      effect on the formation of different nanocrystal morphologies. In addition, the
      catalytic activities of these NCs are evaluated by structure-sensitive reactions,
      including ethanol electro-oxidation and the catalytic reduction of 4-nitrophenol
      (4-NPh). These three types of Au-Pd alloy NCs exhibit different catalytic
      selectivities towards these two reactions. The catalytic activities toward
      electro-oxidation of ethanol are in the order of HOH > RD > TOH, which follows
      the order of their corresponding surface energies. However, the activities toward
      catalytic reduction of 4-NPh are in the order of RD > TOH > HOH, which should be
      related to the local structure of the surfaces.

PMID- 23129411
TI  - [Adnexal skin tumors, gigantic dimensions].
AB  - Adnexal skin tumors are rare and mostly not common. Their appearance are atypical
      and only histologically to save. 2 cases were demonstrated with impressing
      extension demanding a complex surgical approach.

PMID- 23129413
TI  - Horst Prinzbach (1931-2012).

PMID- 23129412
TI  - Effects of glucocorticoids and idebenone on respiratory function in patients with
      duchenne muscular dystrophy.
AB  - In Duchenne muscular dystrophy (DMD) progressive weakness of respiratory muscles
      leads to a restrictive pulmonary syndrome that contributes to early morbidity and
      mortality. Currently no curative treatment exists for DMD. In a Phase II
      randomized placebo-controlled study (DELPHI) in 21 DMD boys at age 8-16 years,
      idebenone (450 mg/d) showed trends of efficacy for cardiac and respiratory
      endpoints. Since the DELPHI study population comprised both glucocorticoid-naive
      subjects and glucocorticoid-users, we now report a post-hoc analysis
      investigating the effects of glucocorticoids and idebenone on markers of
      respiratory weakness, particularly peak expiratory flow (PEF) percent predicted
      (PEF%p). Baseline values of PEF%p correlated well with the percent predicted
      values for maximal inspiratory mouth pressure (MIP%p), forced vital capacity
      (FVC%p), and forced expired volume in 1 sec (FEV1%p). Baseline PEF%p and FVC%p
      were significantly higher in patients on concomitant glucocorticoids compared to
      glucocorticoid-naive patients. In the latter subgroup, idebenone caused a 8.0 +/-
      12.1% improvement in PEF%p, whilst patients on placebo declined by -12.3 +/-
      17.9% (P < 0.05) in the course of the 12 month study. In patients receiving
      concomitant glucocorticoids, PEF%p remained stable (-0.4 +/- 14.6%) in the
      idebenone group compared to a decline by -6.2 +/- 12.4% (P = 0.24) in the placebo
      group. Idebenone showed a trend for efficacy on FVC%p only in glucocorticoid
      naive patients. Because of the study limitations, these data are exploratory and
      preclude any firm conclusions. In conclusion, PEF appears to be a sensitive
      respiratory function parameter that could be a valid and clinically relevant
      endpoint in intervention studies in DMD. In DELPHI the effect size of idebenone
      on PEF%p was significantly larger in steroid-naive patients, possibly indicating
      a maximum treatment effect reached by steroids or steroid-mediated suppression of
      idebenone's effects. The impact of standard care glucocorticoids on respiratory
      function will have to be considered in the planning of future interventional
      trials in DMD.

PMID- 23129414
TI  - src family kinases regulate renal epithelial paracellular permeability barrier
      through an occludin-independent mechanism.
AB  - Paracellular permeability is mediated by the epithelial cell tight junction.
      Studies in intestinal and other epithelia have suggested that the activity of src
      family kinases (SFKs) increases epithelial paracellular permeability through its
      action on the tight junction protein, occludin, but the involvement of SFKs and
      occludin in regulation of renal epithelial paracellular permeability is unclear.
      In this study, the role of SFKs in regulation of renal epithelial paracellular
      permeability and the involvement of occludin protein in this regulatory event was
      examined in two renal epithelial cell lines, LLC-PK(1) (proximal tubule-like) and
      MDCK (distal tubule-like). The effect of broad spectrum SFK inhibitors on
      paracellular permeability of calcein and fluorescein-dextran3000 were examined.
      SFK inhibitor treatment increased paracellular movement of both compounds in both
      renal epithelial cell lines. The SFK inhibitor effect was concentration-dependent
      and, at low concentrations, was not associated with cell damage/death. Response
      to SFK inhibitors was acquired progressively after cell populations attained
      confluence suggesting maturation of the regulatory mechanism. Increased
      paracellular permeability was not associated with dramatic changes in total cell
      content of occludin protein, its partitioning between detergent-soluble and 
      insoluble fractions, or its subcellular localization. Further, the SFK-induced
      increase in paracellular permeability was unaffected by either occludin protein
      overexpression or occludin protein knockdown. These results demonstrate that SFK
      activity decreases paracellular permeability of renal epithelial cells, as
      opposed to its effect in intestinal epithelial cells, and that this regulation is
      not mediated by occludin protein.

PMID- 23129415
TI  - The role of the manipulation of the gut microbiota in obesity.
AB  - The manipulation of the gut microbiota by diet, antibiotics, or probiotics could
      promote, prevent, or reverse the development of specific diseases, including
      obesity. A link has been proposed between obesity and the growth promoters
      (probiotics and antibiotics) that have been used in animals for more than 40
      years to induce weight gain. Several species of the Lactobacillus genus that are
      frequently used as probiotics for human consumption merit particular attention
      because they are increased in the gut microbiota under high-fat diets, are more
      abundant in obese humans, and are selected by growth-promoter antibiotics;
      moreover, the administration of these bacteria in experimental models is linked
      to the development of obesity. However, other species or strains of the same
      genus are associated with an antiobesity effect. Newborns and infants are a
      particularly susceptible population in which the administration of antibiotics or
      probiotics could be related to the development of obesity in adulthood.

PMID- 23129416
TI  - A case-control study on the association between rheumatoid arthritis and bladder
      pain syndrome/interstitial cystitis.
AB  - AIM: While bladder pain syndrome/interstitial cystitis (BPS/IC) has been
      suggested by a number of studies to have autoimmune character, no population
      based study to date has been conducted investigating its association with
      rheumatoid arthritis (RA). This study aimed to examine the association between
      IC/BPS and having previously been diagnosed with RA. METHODS: We conducted this
      study by using administrative claims data sourced from the Taiwan National Health
      Insurance Database. Our study included 9,269 cases with BPS/IC and 46,345
      randomly selected controls. Conditional logistic regression was performed to
      calculate the odds ratio (OR) for the association between previously diagnosed RA
      and IC/BPS. RESULTS: RA was found among 202 (2.2%) cases and 504 (1.12%)
      controls. Conditional logistic regression analysis suggested that when compared
      with controls, the OR for prior RA among cases was 1.66 (95% CI = 1.47-1.87, P <
      0.001) after adjusting for diabetes, hypertension, coronary heart disease,
      obesity, hyperlipidemia, chronic pelvic pain, irritable bowel syndrome,
      fibromyalgia, chronic fatigue syndrome, depression, panic disorder, migraine,
      sicca syndrome, allergy, endometriosis, asthma, overactive bladder, tobacco use
      disorder, and alcohol abuse. Additionally, BPS/IC was consistently and
      significantly associated with a previous diagnosis of RA regardless of
      prescription drug use; the OR for prior RA among groups prescribed <=1 type of
      disease-modifying antirheumatic drug (DMARD), two types of DMARDs, and >=3 types
      of DMARDs or TNF-alpha inhibitor when compared to controls were 1.49 (95% CI =
      1.28-1.72), 1.91 (95% CI = 1.38-2.68), and 2.36 (95% CI = 1.77-3.17),
      respectively. CONCLUSIONS: There is an association between RA and BPS/IC after
      adjusting for socio-demographic characteristics and medical co-morbidities.

PMID- 23129417
TI  - Cloning, characterization and expression of the LECT2 gene in grass carp.
AB  - An expressed sequence tag of grass carp leukocyte cell-derived chemotaxin 2
      (LECT2) gene was screened from an established intestinal cDNA library. Rapid
      amplification of cDNA ends gave rise to a full-length LECT2 cDNA (gcLECT2) with a
      complete open-reading frame of 474 bp, encoding 158 amino acids about 17.9 kDa.
      Homology search and sequence alignment showed that this deduced protein sequence
      shared a high identity with LECT2 from other vertebrates. Western blotting
      indicated immunological cross-reactivity occurs between grass carp and human
      LECT2 protein. This gcLECT2 genomic sequence is 1,868 bp in size, which consists
      of five exons and four introns. Real-time quantitative PCR analysis revealed that
      gcLECT2 gene is ubiquitously expressed in different tissues of healthy grass carp
      including brain, gut, liver, spleen, kidney, muscle and heart, while the
      expression levels were significantly increased in liver and spleen followed by
      Aeromonas salmonicida infection. 992 bp 5'-flanking region sequence was cloned
      and analyzed, where one CAAT box and one GC island were found. Our results showed
      that the LECT2 is suggested to be most possibly involved in the grass carp's
      immune response.

PMID- 23129418
TI  - MoO(3-x)-based hybrids with tunable localized surface plasmon resonances:
      chemical oxidation driving transformation from ultrathin nanosheets to nanotubes.

PMID- 23129419
TI  - Implementation of pharmacist-led medication reviews in general practice.

PMID- 23129420
TI  - Preventive counselling for public health in pharmacies in South Germany.
AB  - BACKGROUND: No overview of preventive health activities conducted by pharmacists
      in South Germany has been available until now. Moreover, little about the needs
      of the public is known with regard to pharmacy-based preventive services.
      OBJECTIVES: To gain an overview of the preventive health services and campaigns
      carried out by pharmacists in the federal state of Bavaria, and to assess the
      interest of the public for pharmacy-based preventive care counselling. SETTING:
      Pharmacies in the seven Bavarian administrative districts, South Germany.
      METHODS: In September 2010, all 3,470 pharmacies in Bavaria were mailed a
      questionnaire concerning their preventive health activities. The pharmacists were
      given the opportunity to complete the questionnaire either online or to mail them
      in. To assess the needs of pharmacy-based preventive health services in the
      Bavarian population, customers of 50 pharmacies were invited to fill in an
      anonymous self-completion questionnaire in March 2011. MAIN OUTCOME MEASURE:
      Relevant preventive health services which can be provided by pharmacists in order
      to meet the customers' needs. RESULTS: 519 of 3,470 pharmacies (15.0 %) took part
      in the survey. 60.5 % (n = 314) conducted at least one preventive health activity
      in the past and 51.6 % (n = 268) offering a disease prevention education event at
      least once a year. As a result of the pharmacists' survey, a ranking list of the
      most frequent preventive care activities was established. The projects conducted
      often lacked structured project schedules and evaluations. The survey assessing
      customer needs was completed by 1,808 customers in 49 of 50 community pharmacies.
      Pharmacists were identified as the preferred provider in 29 of the 31 preventive
      care services listed in the questionnaire. A ranking list with the top ten
      preventive subjects of highest interest was compiled. CONCLUSIONS: Pharmacists
      are active in many different prevention subjects and there is a great interest in
      pharmacy-based preventive care counselling in the Bavarian population. Very few
      structured, well planned and evaluated preventive projects have been conducted in
      Bavarian community pharmacies. Further surveys are needed to analyse the benefit
      of pharmacy-based preventive care counselling for the Bavarian population.

PMID- 23129421
TI  - The SETX missense variation spectrum as evaluated in patients with ALS4-like
      motor neuron diseases.
AB  - Mutations in the senataxin (SETX) gene can cause amyotrophic lateral sclerosis 4
      (ALS4), an autosomal dominant form of juvenile onset amyotrophic lateral
      sclerosis, or result in autosomal recessive ataxia with oculomotor apraxia type
      2. Great caution regarding the possible disease causation, especially of missense
      variations, has to be taken. Here, we evaluated the significance of all
      previously reported SETX missense mutations as well as six newly identified
      variations in 54 patients suspected of having ALS4. Yet, epidemiologic and in
      silico evidence indicates that all newly identified variations and two previously
      published ALS4-related missense variations (C1554G and I2547T) are most likely
      non-pathogenic, demonstrating the problems of interpretation of SETX missense
      alleles in the absence of functional assays.

PMID- 23129422
TI  - Precocious hand use preference in reach-to-eat behavior versus manual
      construction in 1- to 5-year-old children.
AB  - The variation in hand use as a function of task and developmental age poses a
      problem for understanding how and when "handedness," preferred use of one hand,
      develops. The present cross-section study is the first to contrast hand
      preference use for the natural and frequently used reach-to-eat movement with a
      constructional task that requires a very similar reach-to-grasp movement. Thirty
      children between the ages of 1 and 3 years completed an eating task, in which
      they grasped small food items (CheeriosTM or Froot LoopsTM) that they brought to
      the mouth for eating. Thirty children between the ages of 3 and 5 years completed
      the construction task, in which they grasped LEGO(r) pieces to construct 3D
      models. Hand use preference for grasping in the eating and construction tasks was
      calculated by comparing the percentage of grasps made by the right hand and by
      the left hand. There were two main findings: First, right hand preference for
      grasping in the eating task is present as early as 1 year of age, whereas right
      hand preference for grasping in the construction task does not develop until 4
      years of age. Second, right hand preference for grasping is greater in the eating
      than in the construction task. The results are discussed in relation to the idea
      that a consideration for task constraints (e.g., unimanual vs. bimanual; eating
      vs. construction; natural vs. praxic) should be incorporated into the
      experimental design when measuring hand use in children.

PMID- 23129423
TI  - Development, reliability, and validation of an infant mammalian penetration
      aspiration scale.
AB  - A penetration-aspiration scale exists for assessing airway protection in adult
      videofluoroscopy and fiberoptic endoscopic swallowing studies; however, no such
      scale exists for animal models. The aim of this study was threefold: (1) develop
      a penetration-aspiration scale (PAS) for infant mammals, (2) test the scale's
      intra- and interrater reliabilities, and (3) validate the use of the scale for
      distinguishing between abnormal and normal animals. After discussion and
      reviewing many videos, the result was a 7-point infant mammal PAS. Reliability
      was tested by having five judges score 90 swallows recorded with videofluoroscopy
      across two time points. In these videos, the frame rate was either 30 or 60
      frames per second and the animals were either normal, had a unilateral superior
      laryngeal nerve (SLN) lesion, or had hard palate local anesthesia. The scale was
      validated by having one judge score videos of both normal and SLN lesioned pigs
      and testing the difference using a t test. Raters had a high intrarater
      reliability [average kappa = 0.82, intraclass correlation coefficient (ICC) =
      0.92] and high interrater reliability (average kappa = 0.68, ICC = 0.66). There
      was a significant difference in reliability for videos captured at 30 and 60
      frames per second for scores of 3 and 7 (P < 0.001). The scale was also validated
      for distinguishing between normal and abnormal pigs (P < 0.001). Given the
      increasing number of animal studies using videofluoroscopy to study dysphagia,
      this scale provides a valid and reliable measure of airway protection during
      swallowing in infant pigs that will give these animal models increased
      translational significance.

PMID- 23129424
TI  - Midkine is associated with neuroendocrine differentiation in castration-resistant
      prostate cancer.
AB  - BACKGROUND: Castration-resistant prostate cancer (CRPC) is an incurable disease
      and both androgen-deprivation therapy (ADT) and neuroendocrine differentiation
      (NED) are closely related to CRPC transition. More knowledge concerning
      neuroendocrine (NE)-transformed PC cells, the NED process and its association
      with CRPC, is needed. Expression of growth factor midkine (MDK) is correlated
      with poor clinical outcomes in various human cancers, including PC. In the
      present study, we have evaluated MDK expression and NED in two separate tumor
      groups: early and advanced PC. METHODS: Immunohistochemical analysis of MDK, the
      neuronal marker tubulin-beta III (TUBB3) and the NE-marker chromogranin A (CGA)
      in a human archival material consisting of hormone naive (HN)/stage T1b (n = 29)
      and CRPC (n = 24) tumors. Triple immunofluorescent imaging was performed on a
      selection of specimens. RESULTS: MDK, TUBB3, and CGA were upregulated in CRPC
      compared to HN tumors. MDK was highly associated to the expression of both CGA
      and TUBB3, and identified MDK-positive NE-like looking cells found to co-express
      CGA or, more commonly, CGA together with TUBB3. CGA and TUBB3 staining displayed
      a partial expression overlap, an overlap almost exclusively displaying also MDK
      expression. CONCLUSIONS: MDK upregulation in CRPC is associated with NED (shown
      by its relation to CGA and TUBB3). The results suggest that MDK represents an
      over-bridging marker between different populations of NE-like tumor cells,
      possibly as part of the NED process and associated CRPC transition, something
      that needs to be evaluated experimentally as does the applicability of MDK as a
      future target.

PMID- 23129425
TI  - Phosphodiesterases in neurodegenerative disorders.
AB  - Cyclic nucleotide phosphodiesterases (PDEs) are responsible for the breakdown of
      cyclic nucleotides, cyclic adenosine monophosphate (cAMP) and cyclic guanosine
      monophosphate (cGMP). As such, they are crucial regulators of levels of cyclic
      nucleotide-mediated signaling. cAMP signaling and cGMP signaling have been
      associated with neuroplasticity and protection, and influencing their levels in
      the cell by inhibition of PDEs has become a much studied target for treatment in
      a wide array of disorders, including neurodegenerative disorders. In this review,
      we will focus on the involvement of PDEs in neurodegenerative disorders. In
      comparison with preclinical work, data on human patients are scarce. Alzheimer's
      disease is associated with changes in PDE4, PDE7, and PDE8 expression in the
      brain. Altered functioning of PDE4 as well as PDE11 is associated with major
      depressive disorder. In multiple sclerosis, there are indications of alterations
      in expression of several PDE subtypes in the central nervous system; however,
      evidence is indirect. In Huntington's disease and Parkinson's disease, most
      research has focused on PDE1B and PDE10, because of their abundant presence in
      striatal neurons. In another rare, neurodegenerative striatal motor disorder,
      that is, autosomal-dominant striatal degeneration, genetic defects in PDE8B gene
      are thought to underlie the neurodegenerative processes. Although the latter
      disorder has showed a causative dysfunction of PDEs, this does not hold for the
      neurodegenerative disorders discussed above, in which changes in PDE levels
      seemingly rather represent secondary changes and compensation to prior existing
      dysfunction. However, normalizing cyclic nucleotide signaling via PDE inhibition
      remains interesting for the treatment of neurodegenerative disorders.

PMID- 23129426
TI  - Absence of the SLC22A12 gene mutation in Turkish population with primary gout
      disease.
AB  - The aim of the study was to examine whether SLC22A12 gene mutations might be
      influenced in primary gout disease. We included 32 patients with diagnosis of
      primary gout disease and 100 healthy volunteers. DNA was purified from peripheral
      blood, and all exons of the SLC22A12 gene were sequenced. We did not find any
      mutations in the SLC22A12 gene in all of the patients, but found 5 polymorphisms
      in exons 1 (g.T258C, g.C246T), 2 (g.C1246T) and 8 (g.T8011C) and in intron 9
      (g.C8577T). However, we have not found any significant differences in the
      frequency of the individual genotypes between patients with primary gout disease
      and control group. In addition, the polymorphisms were not associated with
      hyperuricemia in our patients with primary gout disease. There was no previously
      reported mutation/polymorphisms of SLC22A12 gene in Turkish population. Our study
      is the first one in Turkish population and suggests that there is no association
      between primary gout disease and SLC22A12 gene polymorphisms. Sequence changes in
      the promotor and intronic regions of SLC22A12 gene should be investigated further
      with larger case groups. 

PMID- 23129427
TI  - Association of TLR4 gene non-missense single nucleotide polymorphisms with
      rheumatoid arthritis in Chinese Han population.
AB  - Toll-like receptor4 (TLR4) plays an important role in the induction and
      regulation of the innate or adaptive immune responses. Thus, the genetic
      variation in TLR4 gene may influence the development of autoimmune diseases such
      as rheumatoid arthritis (RA). Several studies have investigated the roles of
      genetic polymorphisms of TLR4 gene in RA, but most of these studies were
      restricted to two cosegregating functional missense polymorphisms Asp299Gly and
      Thr399Ile. To determine whether non-missense genetic polymorphisms located in
      regulatory region of TLR4 are related to RA in a Chinese Han population, four
      single nucleotide polymorphisms (SNPs) situated on 3' untranslating region (UTR)
      and 5' UTR were genotyped in 213 RA patients and 247 unrelated ethnically matched
      controls using polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP) and direct sequencing techniques. Significant genetic associations
      were observed with the 3' UTR SNP rs41426344 and rs7873784. The minor allele C
      and homozygotic variant genotype CC of rs41426344 and minor allele C of rs7873784
      were identified to be risk factors for the development of RA in Chinese Han
      people. Furthermore, by comparing the variation allele frequencies to other
      populations, prevalent genetic ethnic specificity was observed in all the four
      SNPs. Our study suggested that the effect of non-missense polymorphisms located
      in regulatory region would not be neglected in disease association analysis.

PMID- 23129429
TI  - Early diagnosis of ankylosing spondylitis: an introduction to the newly designed
      Iran criteria for ankylosing spondylitis.
AB  - More than 14 years of clinical practice in rheumatology led the author to develop
      his experience-based criteria for early ankylosing spondylitis (AS) diagnosis.
      This study aims to introduce this new set of criteria, Iran criteria for
      ankylosing spondylitis, and to assess its sensitivity in comparison with 1984
      modified New York criteria. A cost-effective diagnostic approach towards AS
      diagnosis is also proposed. The criteria score the patients according to the
      findings in history and physical examination, imagings and HLA-B27 testing.
      Sensitivity analysis was performed in a retrospective manner after reviewing the
      medical records of 120 patients at the outpatient Rheumatology Clinic of the
      author (private sector), regarding clinical diagnosis by a single rheumatologist
      as the gold standard. The sensitivity was separately measured for disease
      durations of 2, 2-5, 5-10 and more than 10 years. Iran criteria for AS recorded a
      sensitivity of 100 % in all disease durations. However, the sensitivity of 1984
      modified New York criteria was 48.39 % in early stages of the disease and
      increased to 92.10 % for disease duration of more than 10 years. Iran criteria
      for AS provide a highly sensitive instrument for detecting AS in its early and
      late, clinical and subclinical, radiographic and pre-radiographic stages as well
      as atypical forms.

PMID- 23129428
TI  - Dual downregulation of microRNA 17-5p and E2F1 transcriptional factor in
      pediatric systemic lupus erythematosus patients.
AB  - The main objective of this study is to investigate the relative expression of
      miRNA 17-5p and one of its target genes E2F1 in the peripheral blood of systemic
      lupus erythematosus pediatric patients. The expression of miRNA 17-5p and its
      target E2F1 mRNA was analyzed by TaqMan real-time qPCR. Our results showed
      significant downregulation of miRNA 17-5p in SLE patients compared to healthy
      controls; moreover, miRNA 17-5p was more downregulated in patients on no
      treatment compared to those on treatment. Relative expression of E2F1, which is a
      target for miRNA 17-5p, was significantly downregulated as well on both mRNA and
      protein levels in SLE pediatric patients. In conclusion, our data show an
      unexpected dual downregulation of both miRNA 17-5p and its target gene E2F1 on
      the mRNA and protein levels. This may suggest an expression pattern of miRNA 17
      5p and its target E2F1 that may be specific to SLE. [corrected].

PMID- 23129430
TI  - High frequency of inflammatory back pain and other features of spondyloarthritis
      in patients with rheumatoid arthritis.
AB  - The aim of this study was to investigate the frequency of patients with
      rheumatoid arthritis (RA) who have inflammatory back pain (IBP) and meet the
      existing classification criteria for ankylosing spondylitis (AS) and
      spondyloarthritis (SpA). We included 167 patients fulfilling the ACR 1987 revised
      criteria for RA. After obtaining a medical history and performing a physical
      examination, standard pelvic X-rays for examination of the sacroiliac joints
      (SIJ) were ordered in all patients. A computed tomography (CT) or magnetic
      resonance imaging (MRI) of SIJ was performed in patients with suspected
      radiographic sacroiliitis and MRI of SIJ in those who have IBP but no
      radiographic sacroiliitis. IBP was defined according to both Calin and experts'
      criteria. The modified New York (mNY) criteria were used to classify AS, both
      ESSG and Amor criteria for SpA and ASAS classification criteria for axial SpA.
      There were 135 female and 32 male patients with a mean age of 54.8 years. The
      mean disease duration was 9.8 years. RF was positive in 128 patients (79.2 %) and
      anti-CCP in 120 patients (81.1 %). Twenty-eight patients with RA (16.8 %) had IBP
      (Calin criteria), and four (2.4 %) had radiographic sacroiliitis of bilateral
      grade 3. Three patients (1.8 %) fulfilled the mNY criteria for AS, 31 (18.6 %)
      ESSG and 26 (15.6 %) Amor criteria for SpA. Nine patients (five with MRI
      sacroiliitis) (5.3 %) were classified as having axial SpA according to new ASAS
      classification criteria. This study suggests that the prevalence of SpA features
      in patients with RA may be much higher than expected.

PMID- 23129431
TI  - Werner's syndrome may be lost in the shadow of the scleroderma.
AB  - We describe three patients with Werner's syndrome (WS), two of whom had been
      mistakenly diagnosed as having scleroderma. We would like to discuss briefly the
      importance of differentiation of these two disorders from each other.

PMID- 23129432
TI  - Appropriate criteria for the use of cardiac computed tomography angiography in
      patients with high risk of coronary artery disease.

PMID- 23129434
TI  - Urinary exosomes: a reservoir for biomarker discovery and potential mediators of
      intrarenal signalling.
AB  - Over the last decade, there has been increasing research interest in urinary
      exosomes and their relationship with kidney physiology and disease. Protocols for
      isolating urinary exosomes have been refined and the exosomal proteome has been
      extensively catalogued and reported to contain proteins from the kidney's
      glomerulus and all sections of the nephron. In animal and human biomarker
      discovery studies, this proteome changes to reflect the underlying
      pathophysiology of certain kidney diseases. In addition to proteins, exosomes
      from urine have been demonstrated to contain RNA species, another new reservoir
      for biomarker discovery. Exosomes have the capacity to shuttle their cargo
      between kidney cells and change the recipient cell's proteome and function, and
      may represent a mechanism for cell-to-cell signalling along the nephron.
      Significant challenges remain; methods for urinary exosome collection need
      optimisation if "real-life" clinical utility is to be achieved, consensus is
      needed regarding normalisation of changes in exosomal protein and RNA, larger
      scale exosome biomarker validation studies remain to be performed, and whether
      exosomes signal between cells in vivo remains an intriguing, but untested,
      hypothesis.

PMID- 23129435
TI  - Bronchial artery-pulmonary artery malformation as a cause of cryptogenic
      hemoptysis.
AB  - A 12-year-old girl with two episodes of massive hemoptysis was found to have a
      localized pulmonary hemorrhage on bronchoscopy. Multiple investigations including
      a computed tomography (CT) angiogram failed to identify the cause.
      Catheterization of the pulmonary and bronchial vessels uncovered a bronchial
      artery to pulmonary artery fistula, which was embolized by interventional
      radiology. This is the first pediatric case of this type of anomaly and it
      illustrates the importance of angiography in the investigation of cryptogenic
      hemoptysis.

PMID- 23129433
TI  - Concentric hypertrophic remodelling and subendocardial dysfunction in
      mitochondrial DNA point mutation carriers.
AB  - AIMS: Hypertrophic remodelling and systolic dysfunction are common in patients
      with mitochondrial disease and independent predictors of morbidity and early
      mortality. Screening strategies for cardiac disease are unclear. We investigated
      whether myocardial abnormalities could be identified in mitochondrial DNA
      mutation carriers without clinical cardiac involvement. METHODS AND RESULTS:
      Cardiac magnetic resonance imaging was performed in 22 adult patients with
      mitochondrial disease due to the m.3243A>G mutation, but no known cardiac
      involvement, and 22 age- and gender-matched control subjects: (i) Phosphorus-31-
      magnetic resonance spectroscopy, (ii) cine imaging (iii), cardiac tagging and
      (iv) late gadolinium enhancement (LGE) imaging. Disease burden was determined
      using the Newcastle Mitochondrial Disease Adult Scale (NMDAS) and urinary
      mutation load. Compared with control subjects, patients had an increased left
      ventricular mass index (LVMI), LV mass to end-diastolic volume (M/V) ratio, wall
      thicknesses (all P < 0.01), torsion and torsion to endocardial strain ratio (both
      P < 0.05). Longitudinal shortening was decreased in patients (P < 0.0001) and
      correlated with an increased LVMI (r = -0.52, P < 0.03), but there were no
      differences in the diastolic function. Among patients there was no correlation of
      LVMI or the M/V ratio with diabetic or hypertensive status, but the mutation load
      and NMDAS correlated with the LVMI (r = 0.71 and r = 0.79, respectively, both P <
      0.001). The phosphocreatine/adenosine triphosphate ratio was decreased in
      patients (P < 0.001) but did not correlate with other parameters. No patients
      displayed focal LGE. CONCLUSION: Concentric remodelling and subendocardial
      dysfunction occur in patients carrying m.3243A>G mutation without clinical
      cardiac disease. Patients with higher mutation loads and disease burden may be at
      increased risk of cardiac involvement.

PMID- 23129436
TI  - The seven pillars of molecular pharmacology: GPCR research honored with Nobel
      Prize for chemistry.

PMID- 23129437
TI  - Congenital infiltrating lipomatosis of the face: recognition and pathogenesis.

PMID- 23129438
TI  - Ten-year follow-up in a case series of integrative botulinum toxin intervention
      in adolescents with chronic daily headache and associated muscle pain.
AB  - INTRODUCTION: A total of 83% of children report headache during a 6-month period.
      The estimated 1-year prevalence of chronic daily headache (CDH) in children is at
      least 1 to 2%. Muscle pain is associated with headache severity and chronicity.
      Muscle pain can be associated with active muscular trigger points, a functional
      concept still remaining a controversy. An integrated approach including bio
      behavioral management is accepted as standard treatment but does not provide
      sufficient pain relief in all patients. OBJECTIVE: We report the individual
      clinical course of five adolescents with treatment-refractory CDH associated with
      focal muscle pain. We describe a concept of short-term integrative intervention
      including botulinum toxin (StiBo) in a personalized "follow the referred pain
      pattern" injection regimen with the focus on long-term follow-up. RESULTS: StiBo
      showed short-term efficacy on headache frequency and severity. In the long-term
      follow-up, CDH was not existent in any of the patients. CONCLUSION: The treatment
      may have enabled the patients to draw attention away from a repeated circle of
      muscle-triggered pain and withdrawal of daily activities toward self-driven
      activities, thereby potentially preventing the development of further
      chronification. To prove this hypothesis, a prospective, placebo-controlled study
      in young adolescents with CDH should be initiated including objective outcome
      parameters on muscular level.

PMID- 23129439
TI  - LDL Lowering After Acute Coronary Syndrome: Is Lower Better?
AB  - OPINION STATEMENT: Low density lipoprotein cholesterol (LDL-C) levels are a major
      risk factor for the development of acute coronary syndrome (ACS) and for
      recurrent events after ACS. Lowering LDL-C after ACS leads to a significant
      reduction in recurrent events and overall mortality. A lower limit at which LDL-C
      reduction fails to decrease risk has not been determined, and lowering LDL-C
      below current guideline-defined targets may provide incremental benefit. While
      the absolute risk is small, more intensive statin therapy is associated with a
      higher incidence of myopathy, rhabdomyolysis, liver enzyme abnormalities and
      incident diabetes, but not with an increase in malignancies or all-cause
      mortality. It is important that clinicians recognize ACS patients as being at
      very high risk, and provide these patients with intensive lifestyle and
      pharmacologic therapy for all modifiable risk factors. Within this framework,
      either a strategy of "intensive statin treatment after ACS" or a strategy of
      "aggressive LDL-C targets after ACS" would be appropriate based on currently
      available data. Combination lipid-lowering therapy does not have a firm evidence
      base at this point, but may be appropriate in patients with limited statin
      tolerance or very high baseline LDL-C levels. Newer therapies, such as LDL
      apheresis, antisense oligonucleotide sequences to apolipoprotein B (apoB) and
      preprotein convertase subtilin kexin 9 (PCSK9) inhibitors, are currently in
      clinical trials and may represent important advances in LDL-C lowering therapy in
      the future.

PMID- 23129442
TI  - The effects of vitamin D3 during pregnancy and lactation on offspring physiology
      and behavior in sprague-dawley rats.
AB  - Recent findings show that developmental vitamin D deficiency leads to altered
      brain morphology and behavioral development in the rat offspring. We examined the
      effects of different dietary vitamin D levels in rat dams on behavior and
      biochemistry of the offspring. Females were divided into five conditions and
      received diets containing 0, 1,5, 3.3, 6.0, or 10.0 IU/g of vitamin D3 from
      mating to weaning. Offspring were tested as juveniles and as adults for anxiety,
      social learning and behavior, and locomotion. Results show that both deficient
      and excessive levels of vitamin D3 in juveniles lead to altered physiology and
      behavior. In juveniles but not adults, variations in vitamin D were related to
      variations in measures of anxiety and marginally, activity levels. For social
      behaviors, both juveniles and adults were affected by mothers' diets. In general,
      offspring of animals receiving abnormal concentrations of vitamin D showed the
      most deficits.

PMID- 23129443
TI  - Amycolamicin: a novel broad-spectrum antibiotic inhibiting bacterial
      topoisomerase.
AB  - The abuse of antibacterial drugs imposes a selection pressure on bacteria that
      has driven the evolution of multidrug resistance in many pathogens. Our efforts
      to discover novel classes of antibiotics to combat these pathogens resulted in
      the discovery of amycolamicin (AMM). The absolute structure of AMM was determined
      by NMR spectroscopy, X-ray analysis, chemical degradation, and modification of
      its functional groups. AMM consists of trans-decalin, tetramic acid, two unusual
      sugars (amycolose and amykitanose), and dichloropyrrole carboxylic acid. The
      pyranose ring named as amykitanose undergoes anomerization in methanol. AMM is a
      potent and broad-spectrum antibiotic against Gram-positive pathogenic bacteria by
      inhibiting DNA gyrase and bacterial topoisomerase IV. The target of AMM has been
      proved to be the DNA gyrase B subunit and its binding mode to DNA gyrase is
      different from those of novobiocin and coumermycin, the known DNA gyrase
      inhibitors.

PMID- 23129444
TI  - Phosphorylation of Cdc6 at serine 74, but not at serine 106, drives translocation
      of Cdc6 to the cytoplasm.
AB  - Phosphorylation-dependent cytoplasmic translocation of human Cdc6 during S phase
      is sufficient to control its activity after origin firing. Export from the
      nucleus also serves as a mechanism for preventing re-replication in mammalian
      cells. Phosphorylation of the CDK consensus serine residues 54, 74, and 106 has
      been suggested to be involved in the cytoplasmic translocation of Cdc6. To
      determine the relative importance of the three phosphorylation sites, we have
      generated Cdc6 variants by substituting one or more of the three serine residues
      with alanine or aspartic acid and have assessed their cytoplasmic translocation
      behavior. Phosphorylation of serine 74 mainly contributes to the cytoplasmic
      translocation of Cdc6, while serine 54 phosphorylation provides a minor
      contribution. In contrast, phosphorylation at serine 106 does not affect the
      nuclear export of Cdc6. Comparative results were found in cells coexpressing the
      phosphorylation defective mutants of Cdc6 and cyclin A as well as in non
      transfected cells synchronized by their release from a double thymidine block. We
      conclude that Cdk-mediated phosphorylation of Cdc6 at serine 74 is required for
      the cytoplasmic translocalization of Cdc6 during the cell cycle. Phosphorylation
      of Cdc6 at serine 54 plays a minor role and phosphorylation of serine 106 plays
      no role in the cytoplasmic localization of Cdc6. The phosphorylation of S74 in
      Cdc6 could be important for binding to the nuclear export protein for
      translocalization.

PMID- 23129445
TI  - Ultrasound-guided refilling of an intrathecal baclofen pump--a case report.
AB  - INTRODUCTION: Refilling intrathecal baclofen (ITB) pumps can be difficult because
      many patients gain excessive weight after implantation due to their reduced
      expenditure of energy on muscle spasticity. METHODS: We report a case of a 12
      year-old girl with spastic quadriplegia who gained 20 lbs after pump
      implantation. It was necessary to identify the access port of her pump by
      ultrasonography during drug refilling so as to avoid multiple needle punctures.
      RESULTS: The access port of the pump was readily visible by ultrasonography and
      stood out from other parts of the pump. CONCLUSION: Localisation of the access
      ports of ITB pumps by ultrasonography proved to be a feasible and easy technique
      for refilling the drug reservoir in patients with excessive weight gain and
      abundant subcutaneous fat after ITB therapy.

PMID- 23129446
TI  - Surgical pathway and management of pineal region tumours in children.
AB  - BACKGROUND: Pineal region tumours are rare. Surgery is associated with high
      morbidity, and consensus on ideal management pathways remains variable. METHOD:
      Patients with pineal region tumours were identified from the neuro-oncology
      database, and their data were retrospectively reviewed. Data collection included
      presentation, germ cell markers, tumour size and location, imaging, histology,
      treatment and control/relapse rates. RESULTS: Twenty-four patients were treated
      at Alder Hey Children's Hospital between 1998 and 2010. Median age at diagnosis
      was 12.7 years. Sixteen patients presented with hydrocephalus. Twelve were
      successfully treated with endoscopic third ventriculostomy (EVT), and four
      required shunt insertion during follow-up. Fifteen patients had endoscopic
      biopsies. Eleven biopsies were performed at the same time as third
      ventriculostomy, and four patients without significant hydrocephalus had
      endoscopic image-guided biopsies. Eight patients had stereotactic biopsies
      (either because of slit ventricles at diagnosis or because of a
      ventriculoperitoneal shunt already in place), and only one patient had an open
      biopsy. No morbidity or mortality was associated with the biopsies. Histology
      showed four pineal parenchymal tumours, nine gliomas and eleven germ cell
      tumours. Thirteen patients underwent surgical resection. Significant tumour
      debulking was achieved in all of these patients, with gross total resection in 70
      % of cases. There was one intraventricular haemorrhage (full recovery) and one
      mild hemiparesis. There was no surgical mortality. CONCLUSION: The mainstay of
      hydrocephalus management is EVT which provides a safe and reliable route for
      biopsy. In our experience, craniotomy and tumour resection are effective and
      safe.

PMID- 23129447
TI  - Intracranial aneurysm in childhood and interrupted aortic arch.
AB  - BACKGROUND: Intracranial aneurysms are very rare in children. Headache and
      nausea/vomiting are the most prominent clinical findings. The only effective
      treatment is obliteration of aneurysm by surgical or endovascular techniques.
      Interrupted aortic arch is also a rare, congenital cardiovascular malformation
      characterized by the lack of continuity between the ascending and descending
      thoracic aorta. Aortic interruption is an uncommon cause of intracranial
      aneurysm. The course of disease is lethal unless effective collateral flow
      develops. Long-term survival may be possible with surgical repair. METHOD: We
      report on a 17-year-old boy affected with interrupted aortic arch disease and
      associated multiple intracranial aneurysms. Both aneurysms clipped successfully.
      After patient had recovered, he referred to cardiovascular surgery for further
      treatment. CONCLUSION: Surgical or endovascular obliteration remains the main
      therapy for intracranial aneurysms. Accompanying systemic diseases such as
      interrupted aortic arch challenge the management of both diseases.

PMID- 23129448
TI  - Escherichia coli K-12 (pEGFPluxABCDEamp): a tool for analysis of bacterial
      killing by antibacterial agents and human complement activities on a real-time
      basis.
AB  - Photorhabdus luminescens luxCDABE genes were integrated into E. coli K-12 using a
      high copy number plasmid containing modified luxABCDE genes under the control of
      the powerful Lac promoter. This strain emitted 10 times higher bioluminescence
      (BL) than P. luminescens. BL production under different growth conditions was
      studied. In both bacterial strains, the increase in BL signal correlated with the
      increase in optical density (OD) in a rich growth medium. However, at the
      logarithmic growth phase, the BL signal was roughly constant. By contrast, in
      minimal growth media, there was no substantial growth and the BL/cell was
      approximately five times higher than in the rich medium. The dynamic measurement
      range of BL was 10(2) -10(7) colony-forming units (CFU) in E. coli and 10(3) 
      10(7)  CFU in P. luminescens. Because the decrease in the BL signal correlated
      with the decrease in CFU and OD, i.e. the number of bacterial cells killed, it
      proved to be very suitable for assessing the antibacterial effects of different
      antimicrobial agents. Unlike with plate counting, the kinetics of killing can be
      monitored on a real-time basis using BL measurements. Complement activities in
      different samples can be estimated using only one serum dilution. The transformed
      E. coli strain appeared to be superior to P. luminescens in these applications
      because E. coli was complement sensitive, the detection limit of E. coli was one
      order lower and the BL-producing system of P. luminescens appeared to be quite
      unstable.

PMID- 23129449
TI  - Kisspeptin-10 induces dose dependent degeneration in prepubertal rat prostate
      gland.
AB  - BACKGROUND: Kisspeptin peptides mediate their actions through the GnRH loop
      system. How kisspeptins affect prostate gland in prepubertal male mammals remains
      elusive. METHODS: To address this kisspeptin was administered as subchronic (12
      days) twice daily i.p. dose at three different dosage regimens: 10 pg, 1 ng and 1
      ug, to prepubertal male Sprague-Dawley rats (PND 35). Control rats were
      maintained in parallel. At the end of the experiment prostate gland was dissected
      out and processed for light and electron microscopy. DNA damage was also
      estimated by DNA ladder assay and DNA fragmentation assay. RESULTS: Prostate
      weights decreased significantly (P < 0.05) at 1 ug treatment dose of kisspeptin.
      The epithelial height of secretory acini of prostate decreased at 10 pg (P <
      0.05), 1 ng, and 1 ug doses (P < 0.001). Histomorphology and ultrastructure
      demonstrated, decrease in epithelial cell height, epithelial folding and
      dilatation of the organelles with kisspeptin treatment. Percent DNA damage to the
      prostatic tissue was 20.74 +/- 2.18, 43.60 +/- 2.39, and 58.18 +/- 2.59 at 10 pg,
      1 ng and 1 ug doses, respectively. CONCLUSION: The study reveals that continuous
      administration of kisspeptin does not lead to an early maturation but instead
      severe degeneration of prepubertal prostate gland. Wiley Periodicals, Inc.

PMID- 23129450
TI  - Kidney function in primary nephrotic syndrome with insulin resistance.

PMID- 23129451
TI  - N-isopropylacrylamide-modified polyethylenimines as effective gene carriers.
AB  - 25 kDa branched polyethylenimines are modified by N-isopropylacrylamide via
      Michael addition. An agarose gel retardation assay shows that all derivatives
      display good binding affinity toward plasmid DNA. The modified PEI-25K shows
      lower cytotoxicity in MTT assay and better transfection efficiency than
      unmodified PEI-25K in HeLa cells. The endocytosis efficiency of the optimized
      complexes is determined to be 99.9% by flow cytometry. More interestingly,
      although the derivatives are not designed to conjugate with targeting ligands or
      nuclear localization signals, confocal laser scanning microscopy (CLSM)
      demonstrates that the optimized derivative results in increased endocytosis and
      strongly enhanced nuclear uptake compared with PEI-25K.

PMID- 23129453
TI  - Reply: To PMID 22290763.

PMID- 23129454
TI  - Chemical synthesis and enzymatic testing of CMP-sialic acid derivatives.
AB  - The cycloSal approach has been used in the past for the synthesis of a range of
      phosphorylated bioconjugates. In those reports, cycloSal nucleotides were allowed
      to react with different phosphate nucleophiles. With glycopyranosyl phosphates as
      nucleophiles, diphosphate-linked sugar nucleotides were formed. Here, cycloSal
      nucleotides were used to prepare monophosphate-linked sugar nucleotides
      successfully in high anomeric purity and high chemical yield. The method was
      successfully used for the synthesis of three nucleotide glycopyranoses as model
      compounds. The method was then applied to the syntheses of CMP-N-acetyl
      neuraminic acids (CMP-Neu5NAc) and of four derivatives with different
      modifications at their amino functions (N-propanoyl, N-butanoyl, N-pentanoyl and
      N-cyclopropylcarbonyl). The compounds were used for initial enzymatic studies
      with a bacterial polysialyltransferase (polyST). Surprisingly, the enzyme showed
      marked differences in terms of utilisation of the four derivatives. The N
      propanoyl, N-butanoyl, and N-pentanoyl derivatives were efficiently used in a
      first transfer with a fluorescently labelled trisialo-acceptor. However,
      elongation of the resulting tetrasialo-acceptors worsened progressively with the
      size of the N-acyl chain. The N-pentanoyl derivative allowed a single transfer,
      leading to a capped tetramer. The N-cyclopropylcarbonyl derivative was not
      transferred.

PMID- 23129452
TI  - Effects of nabumetone and dipyrone on experimentally induced gastric ulcers in
      rats.
AB  - Nabumetone and dipyrone are non-acidic, nonsteroidal anti-inflammatory drugs.
      Both of them are known to have weak inhibitory effects of cyclooxygenases.
      Gastric side effects represent the most common adverse drug effects of the widely
      used nonsteroidal anti-inflammatory drugs. The gastric effects of these drugs may
      be comparable in experimental ulcer models. In the present study, the gastric
      ulcerogenic activity of nabumetone and dipyrone were investigated on stress- and
      diethyldithiocarbamate-induced experimental ulcer models by determining the ulcer
      index and gastric mucus secretion in rats. It was found that
      diethyldithiocarbamate increased both ulcer index and mucus secretion. Nabumetone
      inhibited dose-dependently the increase of diethyldithiocarbamate-induced mucus
      secretion. Dipyrone inhibited both stress- and diethyldithiocarbamate-induced
      ulcer index and mucus secretion. Nabumetone inhibited stress-induced ulcer index
      at 25-mg/kg dose but stimulated dose-dependently mucus secretion. These effects
      may be attributed to their non-acidic structures and weak inhibitory effects on
      gastric mucosal cyclooxygenases.

PMID- 23129455
TI  - Mesenchymal stem cells from patients to assay bone graft substitutes.
AB  - Bio-engineered scaffolds used in orthopedic clinical applications induce
      different tissue responses after implantation. In this study, non-stoichiometric
      Mg(2+) ions and stoichiometric apatites, which are used in orthopedic surgery as
      bone substitutes, have been assayed in vitro with human adult mesenchymal stem
      cells (hMSC) to evaluate cytocompatibility and osteoconductivity. hMSCs from the
      bone marrow aspirates of orthopedic patients were isolated and analyzed by flow
      cytometry for the surface markers Stro1, CD29, CD44, CD71, CD73, CD90, CD105
      (positive) and CD45, CD235 (negative). The hMSC were analyzed for self-renewal
      capacity and for differentiation potential. The hMSC, which were grown on
      different biomaterials, were analyzed for (i) cytotoxicity by AlamarBlue
      metabolic assay, (ii) osteoconductivity by ELISA for activated focal adhesion
      kinase, (iii) cytoskeleton organization by fluorescence microscopy, and (iv) cell
      morphology which was investigated by scan electron microscopy (SEM). Results
      indicate that isolated cell populations agree with minimal criteria for defining
      hMSC cultures. Non-stoichiometric Mg(2+) and stoichiometric apatites, in granular
      form, represent a more favorable environment for mesenchymal stem cell adhesion
      and growth compared to the non-stoichiometric Mg(2+) apatite, in nano-structured
      paste form. This study indicates that different forms of biomaterials modulate
      osteoconductivity and cellular growth by differential activation focal adhesion
      kinase.

PMID- 23129456
TI  - [The Hamatometacarpale-IV fracture-dislocation: a rare injury of amateur boxers].

PMID- 23129457
TI  - [Sellar xanthogranuloma: MRI imaging and differential diagnosis].

PMID- 23129458
TI  - [Incidental finding of a notochord persistens].

PMID- 23129459
TI  - Feasibility of high-dose dobutamine stress SSFP Cine MRI at 3 Tesla with patient
      adaptive local RF Shimming using dual-source RF transmission: initial results.
AB  - PURPOSE: To investigate the feasibility of high-dose dobutamine stress (HDDS)
      imaging using SSFP sequences at 3 T employing patient-adaptive local RF-shimming
      using a dual-source RF transmission system. MATERIALS AND METHODS: 13 Patients
      underwent a HDDS protocol on a 3 T MRI scanner (Achieva 3.0T-TX, Philips
      Healthcare), equipped with a dual-source RF transmission system. SSFP cine
      sequences using patient-adaptive local RF-shimming (RF-S) were compared to cine
      images acquired without additional shimming. Image quality was evaluated on a 4
      point grading scale and number of non-diagnostic segments assessed. Contrast (CN)
      between myocardium (SIM) and blood pool (SIB) was calculated [(SIB
      SIM)/(SIB+SIM)]. RESULTS: Image quality both at rest and maximum stress was
      significantly improved with RF-S (ED:3.56+/-0.5 vs. 3.23+/-0.63; ES:3.4+/-0.5 vs.
      3.1+/-0.7) compared to no RF-S (ED:2.9+/-0.72 vs. 2.15+/-0.78; ES:2.64+/-0.74 vs.
      1.95+/-0.76; p<0.01). The amount of non-diagnostic segments was significantly
      reduced when using RF-S at rest and stress (3 vs. 39; 19 vs. 78, p<0.05). All
      HDDS studies were diagnostic if performed with RF-S (n=13/13) in comparison to
      conventional shimming (n=5/13). Image contrast was improved for SSFP sequences
      with RF-S (0.53+/-0.08) compared to conventional images (0.46+/-0.09, p=0.06).
      CONCLUSION: Patient-adaptive local RF-shimming using a dual-source RF
      transmission system allows for reliable SSFP imaging in a clinical high-dose
      dobutamine stress protocol at 3 T. RF-S significantly improves image quality and
      reduces the number of non-diagnostic myocardial segments.

PMID- 23129460
TI  - [Multidetector computed tomography of urolithiasis: technique and results].
AB  - The diagnosis of acute urolithiasis results from unenhanced multidetector
      computed tomography (MDCT). This test analyses the functional and anatomical
      possibility for passing an ureteral calculi, the localization and dimension of
      which are important parameters for further therapy. Alternatively chronic
      urolithiasis could be ruled out by magnetic resonance urography (MRU). MRU is the
      first choice especially in pregnant women and children because of radiation
      hygiene. Enhanced MDCT must be emphasized as an alternative to intravenous
      urography (IVU) for diagnosis of complex drainage of urine and suspected disorder
      of the involved kidney. This review illustrates the principles of different tests
      and the clinical relevance thereof.

PMID- 23129462
TI  - Aerobic oxidation of carbon monoxide in a tetrametallic complex.

PMID- 23129461
TI  - An abbreviated MLVA identifies Escherichia coli ST131 as the major extended
      spectrum beta-lactamase-producing lineage in the Copenhagen area.
AB  - Rapid bacterial typing is a valuable and necessary tool in the prevention and
      detection of outbreaks. The purpose of this study was to adapt a multilocus
      variable number of tandem repeats analysis (MLVA) for analysis on a benchtop
      capillary electrophoresis instrument and compare the modified assay with
      multilocus sequence typing (MLST) for typing cefpodoxime-resistant Escherichia
      coli (E. coli). Further, we identified the causative resistance mechanisms and
      epidemiological type of infection for isolates producing extended-spectrum beta
      lactamases (ESBLs). A collection of E. coli resistant to cefpodoxime was typed by
      MLST and a modified MLVA assay using a benchtop capillary electrophoresis
      instrument. Resistance mechanisms were identified by polymerase chain reaction
      (PCR) and sequencing. Patient history was examined to establish the
      epidemiological type of infection for ESBL-producing E. coli. MLVA yielded typing
      results homologous with MLST and it correctly identified E. coli sequence type
      (ST) 131 that was accounting for 45 % of all ESBL-producing isolates in the
      sample collection. The majority (76.7 %) of ESBL-producing isolates was
      healthcare-related and only 23.3 % of the ESBL-producing isolates were community
      onset infections (COI), regardless of the ST. Patients with COI were
      significantly more often of female gender and younger age compared to healthcare
      associated infections (HCAI) and hospital-onset infections (HOI). In conclusion,
      the modified MLVA is a useful tool for the rapid typing of E. coli and it
      identified ST131 as the predominating ESBL-producing lineage in Copenhagen.
      Healthcare-related infections were the predominant infection setting of ESBL
      producing E. coli and the demographic characteristics differed between patients
      with COI and healthcare-related infections.

PMID- 23129463
TI  - Blood volume pulse (BVP) derived vagal tone (VT) between 5 and 7 years of age: a
      methodological investigation of measurement and longitudinal stability.
AB  - The present study evaluated the possibility of collecting cardiac vagal tone data
      using a photoplethysmograph, and its stability and continuity in a longitudinal
      sample of early-school aged children. A method for the optical (i.e., blood
      volume pulse) estimation of heart rate was established in a pilot study. Then the
      longitudinal stability and continuity in photoplethysmograph-derived vagal tone
      was assessed in 114 children (56 girls) at three sessions between 5 and 7 years
      of age. Results indicate that this method possesses substantial measurement
      reliability and individual stability, as children report low intra-individual
      variation over time. Children also report a mean decrease in vagal tone from 5 to
      7 years of age, consistent with increased attentional capacity. Overall, this
      suggests blood volume pulse estimation of vagal tone is both accurate and
      appropriate for naturalistic developmental research.

PMID- 23129464
TI  - Case report: artificial elevation of prothrombin time by telavancin.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus infections are a well
      documented risk of surgery and are becoming increasingly difficult to treat owing
      to continued acquired resistance. A new antibiotic for treatment of
      Staphylococcus aureus is telavancin. CASE DESCRIPTION: A patient at our
      institution was prescribed telavancin for multiple spinal abscesses before spinal
      surgery. Routine preoperative testing revealed an international normalized ratio
      (INR) of 2.05 with no clear cause. Careful review of the patient's medication
      history and prescriber information revealed that telavancin may interfere with
      prothrombin time (PT/INR) testing. In vitro testing by our laboratory confirmed
      an association between telavancin dose and an increase in PT/INR. An alternative
      reagent for PT/INR testing unaffected by telavancin dose revealed a PT/INR of
      0.97. LITERATURE REVIEW: Telavancin interacts with artificial phospholipid
      surfaces used to monitor coagulation while having no actual effect on
      coagulation. PURPOSES AND CLINICAL RELEVANCE: All physicians, especially
      orthopaedic surgeons, should be aware of the effects of telavancin and ensure
      proper measures are taken to acquire the true INR by switching the reagent used
      to test PT/INR or ensuring the PT/INR is drawn before telavancin dosing.

PMID- 23129466
TI  - Reply to letter to the editor: Is there really no benefit of vertebroplasty for
      osteoporotic vertebral fractures? A meta-analysis.

PMID- 23129465
TI  - Ultrasound as a first-line test in the diagnosis of carpal tunnel syndrome: a
      cost-effectiveness analysis.
AB  - BACKGROUND: The American Academy of Orthopaedic Surgeons (AAOS) recommends that
      surgeons obtain a confirmatory test in patients for whom carpal tunnel surgery is
      being considered. The AAOS, however, does not specify a preferred test.
      Ultrasound reportedly causes less patient discomfort and takes less time to
      perform, while maintaining comparable sensitivity and specificity to
      electrodiagnostic testing (EDX). QUESTIONS/PURPOSES: We determined whether
      ultrasound as a first-line diagnostic test is more cost-effective than using EDX
      alone or using ultrasound alone: (1) when used by a general practitioner; and (2)
      when used by a specialist. METHODS: A fictional population of patients was
      created and each patient was randomly assigned a probability of having true
      positive, false-positive, true-negative, and true-positive ultrasound and EDX
      tests over an expected range of sensitivity and specificity values using Monte
      Carlo methods. Charges were assigned based on Medicare charges for diagnostic
      tests and estimates of missed time from work. RESULTS: The average charge for the
      use of ultrasound as a first-line diagnostic test followed by EDX for
      confirmation of a negative ultrasound test was $562.90 per patient in the general
      practitioner scenario and $369.50 per patient in the specialist scenario,
      compared with $400.30 and $428.30 for EDX alone, respectively. CONCLUSIONS: The
      use of diagnostic ultrasound as a first-line test for confirmation of a clinical
      diagnosis of carpal tunnel syndrome is a more cost-effective strategy in the
      specialist population and results in improved false-negative rates in the
      generalist population despite increased cost. LEVEL OF EVIDENCE: Level III,
      economic and decision analyses. See the Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 23129467
TI  - Reply to letter to the editor: the withdrawn ASRTM THA and hip resurfacing
      systems: how have our patients fared over 1 to 6 years?

PMID- 23129468
TI  - The role of arthroscopy in trapeziometacarpal arthritis.
AB  - BACKGROUND: Trapeziometacarpal (TM) arthroscopy should be viewed as a useful
      minimally invasive adjunctive technique rather than the operation itself since it
      allows one to visualize the joint surface under high-power magnification with
      minimal disruption of the important ligamentous complex. Relatively few articles
      describe the arthroscopic treatment of TM osteoarthritis (OA) and the
      arthroscopic anatomy of the TM joint. There is lingering confusion as to whether
      soft tissue interposition and K-wire fixation of the joint are needed and whether
      the outcomes of arthroscopic procedures compare to the more standard open
      techniques for TM arthroplasty. QUESTIONS/PURPOSES: This paper describes (1) the
      arthroscopic ligamentous anatomy of the TM joint, (2) the portal anatomy and
      methodology behind TM arthroscopy, and (3) the arthroscopic treatment for TM OA,
      including the current clinical indications for TM arthroscopy and the expected
      outcomes from the literature. METHODS: A MEDLINE((r)) search was used to retrieve
      papers using the search terms trapeziometacarpal, carpometacarpal, portal
      anatomy, arthroscopy portals, arthroscopy, arthroscopic, resection arthroplasty,
      and arthroscopic resection arthroplasty. Eighteen citations satisfied the search
      terms and were summarized. RESULTS: Careful wound spread technique is needed to
      prevent iatrogenic injury to the surrounding superficial radial nerve branches.
      Traction is essential to prevent chondral injury. Fluoroscopy should be used to
      help locate portals as necessary. Cadaver training is desirable before embarking
      on a clinical case. Questions regarding the use of temporary K-wire fixation or
      thermal shrinkage or the need for a natural or synthetic interposition substance
      cannot be answered at this time. CONCLUSIONS: Longitudinal prospective studies
      are needed to answer these lingering questions. An intimate knowledge of the
      portal and arthroscopic anatomy is needed to perform TM arthroscopy. Minimally
      invasive techniques for resection arthroplasty in TM OA with and without soft
      tissue interposition can yield good outcomes in the treatment of TM OA.

PMID- 23129470
TI  - Letter to the editor: efficacy and degree of bias in knee injury prevention
      studies: a systematic review of RCTs.

PMID- 23129471
TI  - Retraction notice: Does incisional wound VAC after major hip surgery in obese
      pediatric patients reduce wound infection and scar formation? A pilot study.

PMID- 23129472
TI  - Letter to the editor: the ACL in the arthritic knee: how often is it present and
      can preoperative tests predict its presence?

PMID- 23129473
TI  - What are the risks of prophylactic pinning to prevent contralateral slipped
      capital femoral epiphysis?
AB  - BACKGROUND: Two decision analyses on managing the contralateral, unaffected hip
      after unilateral slipped capital femoral epiphysis (SCFE) have failed to yield
      consistent recommendations. Missing from both, however, are sufficient data on
      the risks associated with prophylactic pinning using modern surgical techniques.
      QUESTIONS/PURPOSES: We determined the incidence and nature of complications after
      contemporary prophylactic fixation of the contralateral, unaffected hip in
      patients with a unilateral SCFE. METHODS: We retrospectively identified and
      reviewed 99 children (mean age, 11 years; range, 8-15 years) who underwent
      prophylactic pinning of the contralateral hip after treatment of a unilateral
      SCFE at four tertiary-care children's hospitals from 2001 to 2010. Complications
      on the prophylactic side, such as avascular necrosis (AVN), chondrolysis,
      fractures, implant pain, and need for further surgery, were recorded. Minimum
      followup was 12 months (median, 26 months; range, 12-110 months). RESULTS: On the
      prophylactic side, we found two cases of focal AVN (2%) and no cases of
      chondrolysis (0%). Two patients sustained periimplant femur fractures (2%). Three
      patients had symptomatic hardware (3%), two of whom required surgery for implant
      removal. In three patients (3%), growth occurred off the end of the prophylactic
      screw before physeal closure, but they did not require revision fixation. No
      patients developed a subsequent slip on the side of the prophylactic pinning.
      CONCLUSIONS: While prophylactic pinning prevents SCFE, it is not an entirely
      benign procedure. The possibility of developing complications such as AVN and
      periimplant fracture should be considered when determining the best management
      for the contralateral hip in patients who present with unilateral SCFE. LEVEL OF
      EVIDENCE: Level IV, therapeutic study. See the Instructions for Authors for a
      complete description of levels of evidence.

PMID- 23129474
TI  - Letter to the editor: Critically assessing the Haiti earthquake response and the
      barriers to quality orthopaedic care.

PMID- 23129475
TI  - Orthopaedic case of the month: A 14-year-old boy with a medial thigh soft tissue
      mass.

PMID- 23129476
TI  - Reply to letter-to-the-editor: efficacy and degree of bias in knee injury
      prevention studies: a systematic review of RCTs.

PMID- 23129477
TI  - Emerging ideas: Novel 3-D quantification and classification of cam lesions in
      patients with femoroacetabular impingement.
AB  - BACKGROUND: Femoroacetabular impingement (FAI) can lead to labral injury, osseous
      changes, and even osteoarthritis. The literature contains inconsistent
      definitions of the alpha angle and other nonthree-dimensional (3-D) radiographic
      measures. We present a novel approach to quantifying cam lesions in 3-D terms.
      Our method also can be used to develop a classification system that describes the
      exact location and size of cam lesions. QUESTIONS/HYPOTHESES: We asked whether
      automated quantification of CAM lesions based on CT data is a reasonable way to
      detect CAM lesions and whether they may be classified based on location. METHOD
      OF STUDY: We developed a method to quantify femoral head cam lesions using 3-D
      modeling of CT scans. By segmenting raw DICOM data, we can determine the distance
      from the cam lesion's surface points to the centroid of the femoral head to
      quantify the mean bump height, volume, and location. The resulting 3-D femoral
      and acetabular models will be analyzed with custom software. We then will
      quantify the cam lesion with 3-D parameters using a modified zoning method. The
      mean bump height, volume, and location on the clock face, and relative zoning
      will be calculated. Zonal differences will be statistically analyzed. To assess
      the ability of this method to predict arthroscopic findings, we will obtain
      preoperative CT scans for 25 patients who undergo hip arthroscopy for FAI. We
      will compare measurements with the method with our measurements from arthroscopy.
      The clinical implications of our method's measurements then will be reviewed and
      refined for future prospective studies. SIGNIFICANCE: We present a novel approach
      that can quantify a cam lesion's location and size. This method will be used to
      provide guidelines for the exact amount of bony resection needed from a specific
      location of the proximal femur. There is also potential to develop software for
      ease of use so this method can be more widely applied.

PMID- 23129478
TI  - Femoral fracture rates after discharge from the hospital to the community.
AB  - Previous studies found that the risk of a femoral fracture in residents newly
      admitted to nursing homes was highest during the first months after admission and
      declined thereafter. Many nursing home admissions are preceded by a
      hospitalization. Therefore, the present study aimed to analyze if a similar risk
      pattern of fall-related fractures could also be observed in community-dwelling
      people at home after discharge from the hospital. Routine data of more than
      690,000 German people aged 65 years and older with more than 2 million hospital
      discharges were used to calculate fracture rates in the first 6 months after
      hospitalization, for people discharged to live in the community. Incidence rates
      of femoral fractures as a function of time since discharge from hospital were
      analyzed. Analyses were stratified by sex, age, the need for care, and diagnostic
      groups. For femoral fractures the incidence was highest during the first months
      after discharge and declined thereafter. This pattern was observed in women and
      men, in different age-groups, in different diagnostic groups, and in people with
      and without the need for care. For example, rates for femoral fractures in women
      declined from 17.4 to 11.0 per 1000 person years over the first 6 months after
      admission, and in men over the same time period from 8.2 to 4.5 per 1000 person
      years, respectively. We conclude that the first weeks at home after discharge
      from the hospital are associated with an increased risk for femoral fractures.

PMID- 23129479
TI  - Autonomic modulation for chronic heart failure: a new kid on the block?

PMID- 23129480
TI  - Mobility, longevity and activity of chlorfenapyr in soils treated at a
      termiticidal rate.
AB  - BACKGROUND: The mobility, longevity and termiticidal activity of chlorfenapyr
      applied to soils at the termiticidal labeled rate was evaluated for 30 months
      after treatment (MAT) in a greenhouse study. RESULTS: There was little
      dissipation of chlorfenapyr in soil treated at the labeled rate for perimeter
      treatments for the prevention and control of termite infestations. Chlorfenapyr
      was detected in soil immediately below the initially treated soil in the packed
      soil columns. This was likely due to settling of soil. The treated soil remained
      toxic to subterranean termites in 3 and 7 day bioassays over the duration of the
      study. The treated soil displayed slow-acting properties regarding toxicity to
      termites. Trace amounts of chlorfenapyr were detected in the eluates of packed
      soil cones. CONCLUSION: The commercial formulation of chlorfenapyr used in this
      study (21.45% concentrate diluted to 0.125% prior to application) killed 100% of
      the tested subterranean termites for at least 30 months.

PMID- 23129481
TI  - Selenoprotein P genetic variants and mrna expression, circulating selenium, and
      prostate cancer risk and survival.
AB  - BACKGROUND: Low levels of selenium have been associated with increased risk of
      prostate cancer (PCa). Selenoprotein P is the most abundant selenoprotein in
      serum and delivers ten selenocysteine residues to tissues. Variation in the
      selenoprotein P gene (SEPP1) may influence PCa development or modify the effects
      of selenium. We examined the association of SEPP1 single nucleotide polymorphisms
      (SNPs) with PCa risk and survival, and tested for interactions. METHODS: The
      Physicians' Health Study (PHS) is a prospective cohort of 22,071 US physicians;
      we utilized a nested case-control study of 1,352 PCa cases and 1,382 controls. We
      assessed four SNPs capturing common variation within the SEPP1 locus. In a subset
      of men (n = 80), we evaluated SEPP1 mRNA expression in tumors. RESULTS: Two SNPs
      were significantly associated with PCa risk. For rs11959466, each T allele
      increased risk (odds ratio (OR) = 1.31; 95% confidence interval (CI): 1.02,1.69;
      P(trend)  = 0.03). For rs13168440, the rare homozygote genotype decreased risk
      compared to the common homozygote (OR = 0.56, 95% CI: 0.33, 0.96). Moreover,
      there was a significant interaction of rs13168440 with plasma selenium;
      increasing selenium levels were associated with decreased PCa risk only among men
      with the minor allele (P(interaction)  = 0.01). SEPP1 expression was
      significantly lower in men with lethal PCa than long-term survivors. CONCLUSIONS:
      SEPP1 genetic variation was associated with PCa incidence; replication of these
      results in an independent dataset is necessary. These findings further support a
      causal link between selenium and PCa, and suggest that the effect of selenium may
      differ by genetics.

PMID- 23129482
TI  - Analysis of tomato gene promoters activated in syncytia induced in tomato and
      potato hairy roots by Globodera rostochiensis.
AB  - The potato cyst nematode (Globodera rostochiensis) induces feeding sites
      (syncytia) in tomato and potato roots. In a previous study, 135 tomato genes up
      regulated during G. rostochiensis migration and syncytium development were
      identified. Five genes (CYP97A29, DFR, FLS, NIK and PMEI) were chosen for further
      study to examine their roles in plant-nematode interactions. The promoters of
      these genes were isolated and potential cis regulatory elements in their
      sequences were characterized using bioinformatics tools. Promoter fusions with
      the beta-glucuronidase gene were constructed and introduced into tomato and
      potato genomes via transformation with Agrobacterium rhizogenes to produce hairy
      roots. The analysed promoters displayed different activity patterns in nematode
      infected and uninfected transgenic hairy roots.

PMID- 23129483
TI  - High-level production of lactostatin, a hypocholesterolemic peptide, in
      transgenic rice using soybean A1aB1b as carrier.
AB  - Hypercholesterolemia, a form of cardiovascular disease, is one of the leading
      causes of deaths worldwide. Lactostatin (Ile-Ile-Ala-Glu-Lys), derived from beta
      lactoglobulin in cow's milk, is a bioactive peptide with hypocholesterolemic
      activity higher than sitosterol, a known anti-hypercholesterolemic drug. Here, we
      successfully developed a transgenic rice accumulating a much higher level of
      lactostatin by inserting 29 IIAEK sequences into the structurally flexible
      (nonconserved) regions of soybean seed storage protein, A1aB1b, and introducing
      it into LGC-1 (low glutelin content mutant 1) as host variety. A1aB1b containing
      29 lactostatins was expressed in the endosperm of rice seed cells by using seed
      specific promoters and sorted into novel compartments distinct from normal PB-I
      (ER-derived protein body) and PB-II (protein storage vacuoles). Transgenic rice
      seeds accumulated approximately 2 mg of lactostatins/g of dry seeds, which is
      relatively high compared with previous reports. Our findings suggest that the
      introduction of a high copy number of bioactive peptide into seed storage
      proteins as carrier is one of the effective means in producing higher amounts of
      bioactive peptides in rice.

PMID- 23129484
TI  - Association between KCNE1 (G38S) genetic polymorphism and non-valvular atrial
      fibrillation in an Uygur population.
AB  - BACKGROUND: The relationship between KCNE1 G38S genetic polymorphism and non
      valvular atrial fibrillation is different among different populations. The study
      explored the KCNE1 G38S to understand if the KCNE1 G38S is associated with the
      Uygur atrial fibrillation patients. METHODS: KCNE1 G38S genetic polymorphism was
      determined between 237 non-valvular atrial fibrillation cases and 237 control
      subjects using PCR-RFLP. RESULTS: In univariate analyses, there was a statistical
      difference in genotype distribution between the patients and controls, and a
      significant difference in allele frequency of KCNE1 G38S was observed between the
      two groups (62.6 vs 52.7 %, p = 0.003). In multivariate analyses, the KCNE1 38G
      variant was independently associated with a significant predisposing effect on AF
      after adjusting for related risk factors, and the odds ratio for patients was
      1.634 (95 % CI: 1.192-2.240, p = 0.002). CONCLUSION: The KCNE1 38G is a risk
      factor for incident AF in an Uygur population. The KCNE1 G38S might have
      different impact on AF in different ethnicities.

PMID- 23129485
TI  - Outcome of coumarin-therapy in an outpatient setting over a 10-year period:
      coumarin-therapy in clinical practice.
AB  - OBJECTIVES: A retrospective study was conducted on an unselected sample of
      patients on vitamin K antagonists (VKAs; phenprocoumon, acenocoumarol) in an
      outpatient setting in Austria. The main objective was to determine whether
      bleeding and thromboembolic events reported in randomised trials are comparable
      to the experience in clinical practice. In addition, we focused on differences
      between the two VKAs and the particular indications for treatment and influences
      of risk factors. PARTICIPANTS: Total observation time was 10 years, the number of
      patients was 599 and the patient years-at-risk (pyr) was 1,856. RESULTS: Severe
      bleeding occurred in 1.1 % pyr and the bleeding-related mortality was 0.1 %.
      Severe thromboembolic events occurred in 2.8 % pyr, with a rate of fatal events
      of 0.3 %. A significant increase in risk was found in patients older than 75
      years concerning bleeding as well as thromboembolic events. Acenocoumarol showed
      significantly higher rates in life-threatening and fatal bleeding episodes in
      comparison to phenprocoumon. CONCLUSIONS: The outcome of patients receiving VKA
      in an office setting is similar to that reported in the literature and the use of
      VKAs in this setting appears to be safe.

PMID- 23129486
TI  - Epidemiology of myasthenia gravis in Austria: rising prevalence in an ageing
      society.
AB  - OBJECTIVE: The purpose of this study was to investigate recent epidemiological
      trends of myasthenia gravis (MG) in Austria. METHODS: We used the national
      hospital discharge register, which records the discharge diagnoses of all
      inpatient stays in Austria to calculate the yearly inpatient prevalence of MG
      from 1992 to 2009 (main or secondary diagnosis of MG). The population prevalence
      was indirectly estimated. The temporal and geographical variability of the
      inpatient prevalence was correlated with the number of practicing neurologists.
      RESULTS: The inpatient prevalence of 2009 was calculated as 8.0 and the
      population prevalence as 15.69 (95 % CI 13.16-19.42) per 100,000. We observed a
      2.2 fold increase in the inpatient prevalence between 1992 and 2009, which was
      mainly due to a rise in the number of older patients (3 50 years). Partly this
      could be accounted for by an ageing of the population as a whole and a rise in
      the age of hospitalised patients. However, after adjusting for demographic
      factors an unexplained average yearly rise of 3.7-3.9 % remained. We found a
      significant spatial and temporal correlation of MG inpatient prevalence rates
      with the number of practicing neurologists, which increased over the same period.
      CONCLUSIONS: The results from this study support the notion that the prevalence
      rate of MG in Austria is rising and near the higher end of the wide range
      discussed in the literature. Our data argue for the importance of specialist
      neurological care for the diagnosis of this disease.

PMID- 23129487
TI  - WLS inhibits melanoma cell proliferation through the beta-catenin signalling
      pathway and induces spontaneous metastasis.
AB  - Elevated levels of nuclear beta-catenin are associated with higher rates of
      survival in patients with melanoma, raising questions as to how beta-catenin is
      regulated in this context. In the present study, we investigated the formal
      possibility that the secretion of WNT ligands that stabilize beta-catenin may be
      regulated in melanoma and thus contributes to differences in beta-catenin levels.
      We find that WLS, a conserved transmembrane protein necessary for WNT secretion,
      is decreased in both melanoma cell lines and in patient tumours relative to skin
      and to benign nevi. Unexpectedly, reducing endogenous WLS with shRNAs in human
      melanoma cell lines promotes spontaneous lung metastasis in xenografts in mice
      and promotes cell proliferation in vitro. Conversely, overexpression of WLS
      inhibits cell proliferation in vitro. Activating beta-catenin downstream of WNT
      secretion blocks the increased cell migration and proliferation observed in the
      presence of WLS shRNAs, while inhibiting WNT signalling rescues the growth
      defects induced by excess WLS. These data suggest that WLS functions as a
      negative regulator of melanoma proliferation and spontaneous metastasis by
      activating WNT/beta-catenin signalling.

PMID- 23129489
TI  - Treatment of sleep disorders with melatonin.

PMID- 23129488
TI  - Melatonin for sleep problems in children with neurodevelopmental disorders:
      randomised double masked placebo controlled trial.
AB  - OBJECTIVE: To assess the effectiveness and safety of melatonin in treating severe
      sleep problems in children with neurodevelopmental disorders. DESIGN: 12 week
      double masked randomised placebo controlled phase III trial. SETTING: 19
      hospitals across England and Wales. PARTICIPANTS: 146 children aged 3 years to 15
      years 8 months were randomised. They had a range of neurological and
      developmental disorders and a severe sleep problem that had not responded to a
      standardised sleep behaviour advice booklet provided to parents four to six weeks
      before randomisation. A sleep problem was defined as the child not falling asleep
      within one hour of lights out or having less than six hours' continuous sleep.
      INTERVENTIONS: Immediate release melatonin or matching placebo capsules
      administered 45 minutes before the child's bedtime for a period of 12 weeks. All
      children started with a 0.5 mg capsule, which was increased through 2 mg, 6 mg,
      and 12 mg depending on their response to treatment. MAIN OUTCOME MEASURES: Total
      sleep time at night after 12 weeks adjusted for baseline recorded in sleep
      diaries completed by the parent. Secondary outcomes included sleep onset latency,
      assessments of child behaviour, family functioning, and adverse events. Sleep was
      measured with diaries and actigraphy. RESULTS: Melatonin increased total sleep
      time by 22.4 minutes (95% confidence interval 0.5 to 44.3 minutes) measured by
      sleep diaries (n=110) and 13.3 (-15.5 to 42.2) measured by actigraphy (n=59).
      Melatonin reduced sleep onset latency measured by sleep diaries (-37.5 minutes, 
      55.3 to -19.7 minutes) and actigraphy (-45.3 minutes, -68.8 to -21.9 minutes) and
      was most effective for children with the longest sleep latency (P=0.009).
      Melatonin was associated with earlier waking times than placebo (29.9 minutes,
      13.6 to 46.3 minutes). Child behaviour and family functioning outcomes showed
      some improvement and favoured use of melatonin. Adverse events were mild and
      similar between the two groups. CONCLUSIONS: Children gained little additional
      sleep on melatonin; though they fell asleep significantly faster, waking times
      became earlier. Child behaviour and family functioning outcomes did not
      significantly improve. Melatonin was tolerable over this three month period.
      Comparisons with slow release melatonin preparations or melatonin analogues are
      required. TRIAL REGISTRATION: ISRCT No 05534585.

PMID- 23129491
TI  - Meningitis outbreak shines light on compounding pharmacies.

PMID- 23129490
TI  - Primary and secondary prevention with new oral anticoagulant drugs for stroke
      prevention in atrial fibrillation: indirect comparison analysis.
AB  - OBJECTIVE: To do an indirect comparison analysis of apixaban against dabigatran
      etexilate (2 doses) and rivaroxaban (1 dose), as well as of rivaroxaban against
      dabigatranetexilate (2 doses), for their relative efficacy and safety against
      each other, with particular focus on the secondary prevention population for
      stroke prevention in atrial fibrillation. A secondary objective was to do the
      same analysis in the primary prevention cohort. DESIGN: Indirect treatment
      comparisons of phase III clinical trials of stroke prevention in atrial
      fibrillation, with a focus on the secondary prevention cohorts. A secondary
      analysis was done on the primary prevention cohort. DATA SOURCES: Medline and
      Central (up to June 2012), clinical trials registers, conference proceedings, and
      websites of regulatory agencies. STUDY SELECTION: Randomised controlled trials of
      rivaroxaban, dabigatran, or apixaban compared with warfarin for stroke prevention
      in atrial fibrillation. RESULTS: In the secondary prevention (previous stroke)
      subgroup, when apixaban was compared with dabigatran (110 mg and 150 mg twice
      daily) for efficacy and safety endpoints, the only significant difference seen
      was less myocardial infarction (hazard ratio 0.39, 95% confidence interval 0.16
      to 0.95) with apixaban compared with dabigatran 150 mg twice daily. No
      significant differences were seen in efficacy and most safety endpoints between
      apixaban or dabigatran 150 mg twice daily versus rivaroxaban. Less haemorrhagic
      stroke (hazard ratio 0.15, 0.03 to 0.66), vascular death (0.64, 0.42 to 0.99),
      major bleeding (0.68, 0.47 to 0.99), and intracranial bleeding (0.27, 0.10 to
      0.73) were seen with dabigatran 110 mg twice daily versus rivaroxaban. In the
      primary prevention (no previous stroke) subgroup, apixaban was superior to
      dabigatran 110 mg twice daily for disabling or fatal stroke (hazard ratio 0.59,
      0.36 to 0.97). Compared with dabigatran 150 mg twice daily, apixaban was
      associated with more stroke (hazard ratio 1.45, 1.01 to 2.08) and with less major
      bleeding (0.75, 0.60 to 0.94), gastrointestinal bleeding (0.61, 0.42 to 0.89),
      and other location bleeding (0.74, 0.58 to 0.94). Compared with rivaroxaban,
      dabigatran 110 mg twice daily was associated with more myocardial infarction
      events. No significant differences were seen for the main efficacy and safety
      endpoints between dabigatran 150 mg twice daily and rivaroxaban, or in efficacy
      endpoints between apixaban and rivaroxaban. Apixaban was associated with less
      major bleeding (hazard ratio 0.61, 0.48 to 0.78) than rivaroxaban. CONCLUSIONS:
      For secondary prevention, apixaban, rivaroxaban, and dabigatran had broadly
      similar efficacy for the main endpoints, although the endpoints of haemorrhagic
      stroke, vascular death, major bleeding, and intracranial bleeding were less
      common with dabigatran 110 mg twice daily than with rivaroxaban. For primary
      prevention, the three drugs showed some differences in relation to efficacy and
      bleeding. These results are hypothesis generating and should be confirmed in a
      head to head randomised trial.

PMID- 23129492
TI  - Breast cancer screening: one life saved at a cost of three overdiagnosis.

PMID- 23129493
TI  - Cancer drug shows promise for multiple sclerosis.

PMID- 23129494
TI  - Predictors of failure of non-invasive positive pressure ventilation in infants
      with respiratory failure.

PMID- 23129495
TI  - Gastric cancer epidemiology and risk factors.
AB  - Gastric cancer is a prevalent yet heterogeneous disease. From diet and lifestyle
      to genetics and ethnicity, our appreciation of the complexity of gastric cancer
      has evolved. This review will discuss the epidemiology of gastric cancer focusing
      on trends across various risk categories. We realize that gastric cancer is not
      merely a single disease, but rather individual diseases within a single organ-a
      distinction that will aid our understanding of disease heterogeneity and its
      significance.

PMID- 23129497
TI  - Reductive cleavage of amides to alcohols and amines catalyzed by well-defined
      bimetallic molybdenum complexes.

PMID- 23129496
TI  - Flavin conjugates for delivery of peptide nucleic acids.
AB  - Oligonucleotides and their analogues, such as peptide nucleic acids (PNAs), can
      be used in chemical strategies to artificially control gene expression.
      Inefficient cellular uptake and inappropriate cellular localization still remain
      obstacles in biological applications, however, especially for PNAs. Here we
      demonstrate that conjugation of PNAs to flavin resulted in efficient
      internalization into cells through an endocytic pathway. The flavin-PNAs
      exhibited antisense activity in the sub-micromolar range, in the context of a
      treatment facilitating endosomal escape. Increased endosomal release of flavin
      conjugates into the cytoplasm and/or nucleus was shown by chloroquine treatment
      and also--when the flavin-PNA was conjugated to rhodamine, a mild photosensitizer
      -upon light irradiation. In conclusion, an isoalloxazine moiety can be used as a
      carrier and attached to a cargo biomolecule, here a PNA, for internalization and
      functional cytoplasmic/nuclear delivery. Our findings could be useful for further
      design of PNAs and other oligonucleotide analogues as potent antisense agents.

PMID- 23129499
TI  - Adverse effects of drugs on hemostasis and thrombosis.

PMID- 23129501
TI  - Ethanol pre-exposure during adolescence or adulthood increases ethanol intake but
      ethanol-induced conditioned place preference is enhanced only when pre-exposure
      occurs in adolescence.
AB  - Behavioral sensitization has been suggested to contribute to uncontrolled alcohol
      consumption. The aim of this study was to investigate the effects of repeated
      ethanol administration in adolescent and adult mice on subsequent ethanol
      consumption and conditioned place preference (CPP). Mice were administered
      ethanol for 15 consecutive days. This ethanol regimen induced behavioral
      sensitization to a lesser degree in adolescents than in adults. Following ethanol
      treatment, mice were subjected to CPP procedure, or given a free choice between
      water and ethanol solutions. While ethanol-pretreated adult mice did not display
      a robust ethanol-induced CPP, ethanol induced a significant CPP in mice
      pretreated with ethanol during adolescence. Ethanol pretreated mice, regardless
      of age, showed higher ethanol intake to saline-treated mice. The present findings
      suggest that ethanol-induced neuroadaptations underlying behavioral sensitization
      may activate mechanisms responsible for enhanced ethanol intake, and also reveals
      that ethanol pre-exposure during adolescence increases ethanol reward as measured
      by CPP.

PMID- 23129502
TI  - Are melanopsin cells blocked by filtering IOLs?

PMID- 23129503
TI  - Fugo blade-assisted lens aspiration in a case of intra- and retro-lenticular
      hemorrhage.
AB  - Hemorrhage into the crystalline lens is exceedingly rare but has been described
      following ocular trauma [1, 2], glaucoma surgery [3-5], laser iridotomy [6],
      pediatric cataract surgery [7], and also in the absence of an obvious pathology
      [8]. We describe a case of intra- and retro-lenticular organised bleed which
      presented 9 years following repair of open globe injury and which was treated
      using fugo blade-assisted lens aspiration. The fugo blade provided adequate
      endocoagulation of retrolenticular blood during posterior capsulotomy and
      prevented undue anterior segment hemorrhage.

PMID- 23129504
TI  - Intraocular pressure after descemet stripping endothelial keratoplasty (DSEK).
AB  - To assess the incidence of elevated intraocular pressure (IOP) after descemet
      stripping endothelial keratoplasty (DSEK). Retrospective case series. From the
      start of the technique in our hospital in 2003 until the middle of 2010, 73 eyes
      underwent DSEK, of which 66 (90.5 %) had a clear graft 1 year after surgery. IOP
      data pre- and postoperatively were analyzed. Follow-up was 1-5 years (mean 3.8,
      SD 1.3). Mean age was 71 years (SD 11, range 43-89). Three eyes (4.5 %) had a
      history of glaucoma before DSEK. Mean pre-operative IOP was 12.4 mmHg (SD +/-
      4.3). Mean IOP 1 day post-operatively was 16.4 mmHg (+/-9.2). Mean IOP after 1
      and 6 months, and 1, 3, and 5 years were, respectively, 13.9 (+/-5.3), 14.7 (+/
      5.6), 14.2 (+/-5.4), 13.8 (+/-3.7), and 12.6 (+/-3.5). Seventeen percent (11
      eyes) had a postoperative rise in IOP which needed medical or surgical
      intervention: 8 % (5 eyes) had a rise in IOP 1 day after DSEK, of which 1
      underwent a trabeculectomy 7 months after DSEK surgery; 6 % (4 eyes) had a rise
      in IOP later in the postoperative period, which could all be managed medically;
      and 3 % (2 eyes) had increased IOP 1 day after DSEK and later in the
      postoperative period, both eyes underwent a trabeculectomy 5 and 24 months,
      respectively, after DSEK surgery. An increase in IOP was encountered in 17 % of
      DSEK patients. Checking the IOP in the short and long postoperative period is
      necessary.

PMID- 23129505
TI  - Smart phone as an adjunctive imaging tool to visualize scolex in orbital
      myocysticercosis.
AB  - Orbital myocysticercosis is a helminthic infestation with variable clinical
      presentations. Computed tomography is considered gold standard in orbital
      imaging. Evaluation of computed tomography films in out-patient departments (OPD)
      is important in the management of orbital diseases. In this case report, we
      highlight the use of a smart phone as an aid in OPD for studying computed
      tomography images in identifying a small cysticercus cyst of the superior rectus
      muscle, which was invisible on naked eye examination.

PMID- 23129506
TI  - Orbital chondrosarcoma arising from paranasal sinuses.
AB  - Orbital chondrosarcoma arising from paranasal sinuses or from the nasal cavity
      with orbital extension is highly unusual. The aim of this report is to describe
      our multidisciplinary experience in the treatment of three patients with
      extensive sino-orbital chondrosarcomas. The patients were aged 43, 75 and 63
      years, and the tumors originated from the maxillary, sphenoidal, and ethmoidal
      sinuses, respectively. Magnetic resonance imaging studies showed homogeneously
      hypointense lesions on T1-weighted scans, which were hyperintense on T2-weighted
      images. Intranasal endoscopic surgery alone or in combination with other
      conventional surgical approaches was the main therapeutic choice. Two patients
      had recurrences treated with wider surgical removal. Fractionated stereotactic
      radiotherapy was used in two cases. Two patients had histopathological grade I
      tumor and one had grade III chondrosarcoma. No patient had regional spread or
      distant metastasis. All patients were disease-free at 4, 2, and 3 years,
      respectively, following their last therapeutic interventions. Endoscopic surgery
      results in lesser morbidity for chondrosarcomas arising from paranasal sinuses
      and extending into posterior parts of the orbit. However, because control of
      surgical margins may not be complete, recurrences may occur justifying more
      radical approaches. 

PMID- 23129507
TI  - Clarithromycin modulates Helicobacter pylori-induced activation of nuclear factor
      kappaB through classical and alternative pathways in gastric epithelial cells.
AB  - Infection of gastric epithelial cells by Helicobacter pylori stimulates the
      activation of nuclear factor-kappaB (NF-kappaB) and the upregulation of
      interleukin-8 (IL-8) expression. Activation of NF-kappaB can occur through
      classical (p50/p65) and alternative (p52/RelB) pathways. The role of the
      bacterial cag pathogenicity island (PAI) in these events is controversial. This
      study aimed to evaluate the hypothesis that the CagA protein is required for H.
      pylori-induced activation of NF-kappaB and upregulation of IL-8 expression, and
      for clarithromycin (CAM) to exert its molecular effects. Cultured KATO-III human
      gastric cancer cells were treated with extracts of H. pylori strains ATCC43504
      (cag PAI(+)) and ATCC51932 (cag PAI(-)) for 24 h. NF-kappaB and phospho-IkappaB
      protein expression was then evaluated using western blotting. IL-8 mRNA
      expression was evaluated using the reverse transcription polymerase chain
      reaction. Following the separation of the proteins using two-dimensional gel
      electrophoresis, proteomes of the two bacterial extracts were compared using
      nanoflow liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS) analysis.
      Although the protein profiles of the two extracts differed, both extracts induced
      IkappaBalpha phosphorylation, upregulation of IL-8 expression, and NF-kappaB
      activation through classical and alternative pathways. In cells treated with
      either of the bacterial extracts, CAM inhibited H. pylori-induced activation of
      NF-kappaB and upregulation of IL-8 expression. These results suggested that CagA
      is not required for H. pylori-induced activation of NF-kappaB and upregulation of
      IL-8 expression in gastric epithelial cells. H. pylori-induced NF-kappaB
      signaling can occur through classical and alternative activation pathways, and
      that CAM inhibits these two pathways.

PMID- 23129508
TI  - Signal peptide-independent secretory expression and characterization of
      pullulanase from a newly isolated Klebsiella variicola SHN-1 in Escherichia coli.
AB  - A strain with the power to produce extracellular pullulanase was obtained from
      the sample taken from a flour mill. By sequencing its 16S rDNA, the isolate was
      identified as Klebsiella variicola SHN-1. When the gene encoding pullulanase,
      containing the N-terminal signal sequence, was cloned into Escherichia coli BL21
      (DE3), extracellular activity was detected up to 10 U/ml, a higher level compared
      with the results in published literature. Subsequently, the recombinant
      pullulanase was purified and characterized. The main end product from pullulan
      hydrolyzed by recombinant pullulanase was determined as maltotriose with HPLC,
      and hence, the recombinant pullulanase was identified as type I pullulanase,
      which could be efficiently employed in starch processing to produce maltotriose
      with higher purity and even to evaluate the purity of pullulan. To investigate
      the effect of signal peptide on secretion of the recombinant enzyme, the signal
      sequence was removed from the constructed vector. However, secretion of
      pullulanase in E. coli was not influenced, which was seldom reported previously.
      By localizing the distribution of pullulanase on subcellular fractions, the
      secretion of recombinant pullulanase in E. coli BL21 (DE3) was confirmed, even
      from the expression system of nonsecretory type without the assistance of signal
      peptide.

PMID- 23129509
TI  - Pharmacological inhibition of fibroblast growth factor (FGF) receptor signaling
      ameliorates FGF23-mediated hypophosphatemic rickets.
AB  - Fibroblast growth factor 23 (FGF23) is a circulating factor secreted by
      osteocytes that is essential for phosphate homeostasis. In kidney proximal
      tubular cells FGF23 inhibits phosphate reabsorption and leads to decreased
      synthesis and enhanced catabolism of 1,25-dihydroxyvitamin D3 (1,25[OH]2 D3 ).
      Excess levels of FGF23 cause renal phosphate wasting and suppression of
      circulating 1,25(OH)2 D3 levels and are associated with several hereditary
      hypophosphatemic disorders with skeletal abnormalities, including X-linked
      hypophosphatemic rickets (XLH) and autosomal recessive hypophosphatemic rickets
      (ARHR). Currently, therapeutic approaches to these diseases are limited to
      treatment with activated vitamin D analogues and phosphate supplementation, often
      merely resulting in partial correction of the skeletal aberrations. In this
      study, we evaluate the use of FGFR inhibitors for the treatment of FGF23-mediated
      hypophosphatemic disorders using NVP-BGJ398, a novel selective, pan-specific FGFR
      inhibitor currently in Phase I clinical trials for cancer therapy. In two
      different hypophosphatemic mouse models, Hyp and Dmp1-null mice, resembling the
      human diseases XLH and ARHR, we find that pharmacological inhibition of FGFRs
      efficiently abrogates aberrant FGF23 signaling and normalizes the
      hypophosphatemic and hypocalcemic conditions of these mice. Correspondingly, long
      term FGFR inhibition in Hyp mice leads to enhanced bone growth, increased
      mineralization, and reorganization of the disturbed growth plate structure. We
      therefore propose NVP-BGJ398 treatment as a novel approach for the therapy of
      FGF23-mediated hypophosphatemic diseases.

PMID- 23129510
TI  - Molecular cloning and pharmacological characterisation of a tyramine receptor
      from the rice stem borer, Chilo suppressalis (Walker).
AB  - BACKGROUND: Tyramine (TA) and octopamine (OA) are considered to be the
      invertebrate counterparts of the vertebrate adrenergic transmitters. Because
      these two phenolamines are the only biogenic amines whose physiological
      significance is presumably restricted to invertebrates, the attention of
      pharmacologists has been focused on the corresponding receptors, which are
      believed to represent promising targets for novel insecticides. For example, the
      formamidine pesticides, such as chlordimeform and amitraz, have been shown to
      activate OA receptors. RESULTS: A full-length cDNA (designated CsTyR1) from the
      rice stem borer, Chilo suppressalis (Walker), has been obtained through homology
      cloning in combination with rapid amplification of cDNA ends/polymerase chain
      reaction (RACE-PCR). The mRNA of CsTyR1 is present in various tissues, including
      hemocytes, fat body, midgut, Malpighian tubules, nerve cord and epidermis, and it
      is found predominantly in the larval nerve cord with 16-80-fold enrichment
      compared with other tissues. The authors generated a HEK 293 cell line stably
      expressing CsTyR1 in order to examine functional and pharmacological properties
      of this receptor. Both TA and OA at 0.01-100 uM can reduce forskolin-stimulated
      intracellular cAMP levels in a dose-dependent manner (TA, EC(50) = 369 nM; OA,
      EC(50) = 978 nM). In agonist assays, activation of CsTyR1 by clonidine and
      amitraz but not by naphazoline and chlordimeform can also significantly inhibit
      forskolin-stimulated cAMP production. The inhibitory effect of TA at 10 uM is
      eliminated by coincubation with yohimbine, phentolamine or chlorpromazine (each
      10 uM). CONCLUSION: This study represents a comprehensive molecular and
      pharmacological characterisation of a tyramine receptor in the rice stem borer.

PMID- 23129511
TI  - Effects of replacing fish meal with soy cake in a diet based on urea-treated rice
      straw on performance of growing Laisind beef cattle.
AB  - The present study was to test if different ratios of fish meal to soy cake as
      protein supplements in the diet are not significantly different in effects on
      feed intakes and performance of growing beef cattle fed urea-treated rice straw
      (URTRS) as basal diet under local conditions in North Vietnam. Thirty-six male
      cattle of Laisind (50% local Yellow cattle and 50% Sindhi, both Bos indicus) at
      around 12 months of age with an average live weight of 124 +/- 12 kg at start
      were used in six groups of the experiment. Six diets named A, B, C, D, E, and F
      used in the experiment were similar in crude protein (CP) level, except for diet
      A with no supplementation, but different in fish meal/soy cake ratio based on CP
      content as follows: diet A 0/0, diet B 100/0, diet C 75/25, diet D 50/50, diet E
      25/75, and diet F 0/100. Following a 4-week adaptation period, a comparison
      period lasted 24 weeks. The total intakes of dry matter (DM), DM from roughage,
      metabolizable energy (ME), and CP were 6, 7, 6, and 20% higher in diets B-F than
      diet A with P values <= 0.05, 0.05, 0.05, and 0.001, respectively. The average
      daily gain (ADG) was 50% higher (P<0.001) in diets B-F than that in diet A.
      Compared to diet A, diets B-F had lower feed conversion ratio (FCR)DM, FCRME, and
      FCRCP by 30, 20, and 30%, respectively (all at P<0.001). There were no
      significant differences between diets B-F in the intakes, FCRs, and ADG. The
      apparent digestibility of CP was 12 to 24% higher (P<0.001) in diets B-F than
      that in diet A. There was a tendency that the apparent digestibilities of DM, CP,
      and CF were increasing with increasing level of soy cake in this study. The ratio
      of fish meal to soy cake did not significantly affect feed intakes, ADG, FCR, and
      apparent nutrient digestibilities of the cattle. Soy cake can therefore be used
      to partially or fully replace fish meal as a protein supplement in the diet of
      growing beef cattle fed URTRS without any negative effects on animal performance.

PMID- 23129513
TI  - Cyclopropyl-tryptamine analogues: synthesis and biological evaluation as 5-HT(6)
      receptor ligands.
AB  - Conformational restrictions: Based on the pharmacophore model for 5-HT(6) 
      receptor ligands (shown), tryptamine analogues bearing a cyclopropyl ring on the
      alpha-position of the tryptamine side chain were synthesized and evaluated
      against 5-HT receptors. N,N-Dimethyl-1-arylsulfonyltryptamine derivatives
      exhibited promising selectivity for 5-HT(6)  over 5-HT(1a)  and 5-HT(4) 
      receptors and interesting activity against 5-HT(6)  (K(i) =~0.15 MUM; IC(50)
      =~0.20 MUM).

PMID- 23129512
TI  - Polymorphisms in CYP17 and CYP3A4 and prostate cancer in men of African descent.
AB  - BACKGROUND: A meta and pooled analysis of published and unpublished case-control
      studies was performed to evaluate the association of CYP17 (rs743572) and CYP3A4
      (rs2740574) polymorphisms and prostate cancer (PCa) in men from the USA,
      Caribbean, and Africa. METHODS: Eight publications (seven studies) and two
      unpublished studies for CYP17 included 1,580 subjects (559 cases and 1,021
      controls) and eleven publications and three unpublished studies for CYP3A4
      included 3,400 subjects (1,429 cases and 1,971 controls). RESULTS: Overall, the
      CYP17 heterozygous and homozygous variants were not associated with PCa, but they
      confer a 60% increased risk of PCa in a sub-group analysis restricted to African
      American men (T/C + C/C, OR: 1.6, 95% CI: 1.1-2.4). No associations were observed
      for CYP3A4, overall and in stratified analyses for African-Americans and
      Africans. The pooled analysis suggests that after adjusting for study, age, PSA,
      and family history of PCa, CYP17 was associated with PCa for men of African
      ancestry (Adjusted OR: 3.5, 95% CI: 1.2-10.0). CONCLUSIONS: Our findings suggest
      that genetic factors involved in the androgen pathway play a role in PCa risk
      among men of African ancestry.

PMID- 23129514
TI  - Utilization of and charges for robotic versus laparoscopic versus open surgery
      for endometrial cancer.
AB  - BACKGROUND AND OBJECTIVES: To analyze the utilization and hospital charges
      associated with robotic (RS) versus laparoscopic (LS) versus open surgery (OS) in
      endometrial cancer patients. METHODS: Hospital discharge data were extracted from
      Florida Agency for Health Care Administration between October 2008 and December
      2009. RESULTS: Of 2,247 patients (median age: 64 years), 29% had RS, 10% had LS,
      and 61% had OS. The mean length of hospital stay was 1.6, 1.8, and 3.9 days for
      RS, LS, and OS, respectively (P < 0.001). The median hospital charge was $51,569,
      $37,202, and $36,492, for RS, LS, and OS (P < 0.001), with operating room charges
      ($22,600, $13,684, and $11,272) accounting for the major difference. Robotic
      surgery utilization increased by 11% (23-34%) over time. CONCLUSIONS: In this
      statewide analysis of endometrial cancer patients, the utilization of robotic
      surgery increased and is associated with higher hospital charges compared to
      laparoscopic and open procedures.

PMID- 23129515
TI  - Self-assembly of a mononuclear [Fe(III)(L)(EtOH)2] complex bearing an n-dodecyl
      chain on solid highly oriented pyrolytic graphite surfaces.
AB  - The synthesis and structures of the N-[(2-hydroxy-3-methyl-5
      dodecylphenyl)methyl]-N-(carboxymethyl)glycine disodium salt (HL) ligand and its
      neutral mononuclear complex [Fe(III) (L)(EtOH)(2)] (1) are reported. Structural
      and electronic properties of 1 were investigated by using scanning tunneling
      microscopy (STM) and current imaging tunneling spectroscopy (CITS) techniques.
      These studies reveal that molecules of 1 form well-ordered self-assemblies when
      deposited on a highly oriented pyrolytic graphite (HOPG) surface. At low
      concentrations, single or double chains (i.e., nanowires) of the complex were
      observed, whereas at high concentration the complex forms crystals and densely
      packed one-dimensional structures. In STM topographies, the dimensions of
      assemblies of 1 found on the surface are consistent with dimensions obtained from
      X-ray crystallography, which indicates the strong similarities between the
      crystal form and surface assembled states. Double chains are attributed to
      hydrogen-bonding interactions and the molecules align preferentially along
      graphite defects. In the CITS image of complex 1 a strong tunneling current
      contrast at the positions of the metal ions was observed. These data were
      interpreted and reveal that the bonds coordinating the metal ions are weaker than
      those of the surrounding ligands; therefore the energy levels next to the Fermi
      energy of the molecule should be dominated by metal-ion orbitals.

PMID- 23129516
TI  - Adolescent asthma after rhinovirus and respiratory syncytial virus bronchiolitis.
AB  - BACKGROUND AND AIMS: Asthma risk is increased after bronchiolitis in infancy.
      Recent studies have suggested that the risk may be dependent on the causative
      virus. The aim of the study was to evaluate the asthma risk in adolescence in
      subjects hospitalized for rhinovirus or respiratory syncytial virus (RSV)
      bronchiolitis in infancy. SUBJECTS AND METHODS: At the median age of 16.5 years,
      a questionnaire was sent to 96 study subjects hospitalized for bronchiolitis at
      <24 months of age and since then prospectively followed-up. Sixty-seven (70%)
      returned the fulfilled questionnaire. RSV and rhinovirus etiology of
      bronchiolitis had been studied in serum and respiratory samples obtained on
      admission in infancy. The occurrence of asthma was compared between former
      bronchiolitis patients and population controls recruited for this study in
      adolescence. RESULTS: Doctor-diagnosed asthma was present in 30% of former
      bronchiolitis patients and in 5% of controls (OR 7.9, 95% CI 3.3-19.3). The
      respective figures for self-reported asthma were 64% and 11% (OR 14.7, 95% CI 7.2
      30.0). Self-reported asthma was more common in the former rhinovirus than RSV
      patients (83.3% vs. 47.6%, P = 0.023, mixed infections included; 81.3% vs. 50%, P
      = 0.067, mixed infections excluded). CONCLUSIONS: Patients hospitalized for RSV
      and rhinovirus bronchiolitis at <24 months of age had an increased asthma risk at
      15-18 years of age compared with population controls. Within the former
      bronchiolitis group, the risk of self-reported asthma was higher after non-RSV
      versus RSV and after rhinovirus versus non-rhinovirus bronchiolitis.

PMID- 23129517
TI  - Acute Carpal Tunnel Syndrome Due to Excessive Blood-Pressure-Measurement at the
      Wrist.

PMID- 23129519
TI  - Automated ultrasonographic measurement of basic fetal growth parameters.
AB  - PURPOSE: The goal of our study was to compare the accuracy of automated
      ultrasonographic measurements of fetal biometric parameters with those achieved
      manually. MATERIAL AND METHODS: Manual and automated fetal biometric measurements
      were performed in 83 patients between 11 + 0 and 40 + 6 weeks of gestation,
      regardless of BMI, fetal position, placental location and quantity of amniotic
      fluid. All patients were examined using Siemens Healthcare Ultrasound equipment,
      Syngo auto OB measurement, with a 6C2 probe (2.5 - 6 MHz) in a 2 D approach. The
      biometric measurement evaluation included the following parameters: crown-rump
      length (CRL), biparietal diameter (BPD), occipitofrontal diameter (OFD), head
      circumference (HC), abdominal circumference (AC), femur length (FL), and humerus
      length (HL). All patients were divided into four distinct groups according to the
      gestational age: Group 1: 11 + 0 to 14 + 6 weeks, Group 2: 15 + 0 to 23 + 6
      weeks, Group 3: 24 + 0 to 34 + 6 weeks, and Group 4: 35 + 0 to 40 + 6 weeks. The
      results of the automated measurements were classified in four different groups:
      Score 1: the automatic measurements were within a range of +/- 5 % of the manual
      measurements, Score 2: the automatic measurements varied within +/- 10 % from
      those done manually, Score 3: the variability range was more than 10 % but less
      than 50 %, and Score 4: was related to an incorrect measurement. RESULTS:
      Comparing the automated with the manual measurements, Score 1 was found for 41.74
      % of all biometric parameters. 24.37 % of the automated measurements were within
      Score 2, 11.65 % of the automated measurements showed Score 3 and 22.24 % had
      Score 4. Score 1 + 2 results were found in more than 62 % of cases for CRL, BPD,
      OFD, AC, and FL, followed by 55.91 % for HC measurements. The lowest result of
      50.45 % was found for HL. Looking in detail at the four gestational age groups, a
      high range of variation was identified for the automatic biometric results for
      the different growth parameters: Group 1 had very good or good automatic results
      (Score 1 + 2) for CRL (76.93 %) and AC (76.47 %). Unacceptable measurements (=
      Score 3 + 4) were found for BPD (58.82 %), HC (64.71 %) and HL (82.35 %). Group 2
      showed very good or good automatic results (Score 1 + 2) for BPD (90 %), OFD
      (83.34 %), HC (80.00 %), AC (80.00 %), FL (83.33) and HL (80.00 %). Score 3 + 4
      results were found in less than 20 % of the cases in this group. Group 3 showed
      very good or good automatic results (Score 1 + 2) for BPD (87.50 %), OFD (79.17
      %), and FL (87.50 %). Score 3 + 4 results were found high to be high for AC
      (41.66 %), and HL (37.50 %). Group 4 revealed very good or good automatic results
      (Score 1 + 2) only for OFD (83.34 %), while Score 3 + 4 were found high for BPD
      (41.67 %), HC (58.33 %), AC (50 %), FL (58.33 %) and HL (58.33 %). The comparison
      of all gestational age groups showed the best results for automatic measurements
      to be in the second group (15 + 0 to 23 + 6 weeks). Humerus length was the
      parameter with the highest unacceptable automated measurements in all 4 groups.
      CONCLUSION: Syngo auto OB measurement enables rapid automated measurement of
      fetal biometric parameters. Despite the fact that a number of problems remain to
      be solved, the described method may have a significant impact on daily workflow
      efficiency in fetal biometry.

PMID- 23129518
TI  - Guidelines and good clinical practice recommendations for contrast enhanced
      ultrasound (CEUS) in the liver--update 2012: a WFUMB-EFSUMB initiative in
      cooperation with representatives of AFSUMB, AIUM, ASUM, FLAUS and ICUS.
AB  - Initially, a set of guidelines for the use of ultrasound contrast agents was
      published in 2004 dealing only with liver applications. A second edition of the
      guidelines in 2008 reflected changes in the available contrast agents and updated
      the guidelines for the liver, as well as implementing some non-liver
      applications. Time has moved on, and the need for international guidelines on the
      use of CEUS in the liver has become apparent. The present document describes the
      third iteration of recommendations for the hepatic use of contrast enhanced
      ultrasound (CEUS) using contrast specific imaging techniques. This joint WFUMB
      EFSUMB initiative has implicated experts from major leading ultrasound societies
      worldwide. These liver CEUS guidelines are simultaneously published in the
      official journals of both organizing federations (i.e., Ultrasound in Medicine
      and Biology for WFUMB and Ultraschall in der Medizin/European Journal of
      Ultrasound for EFSUMB). These guidelines and recommendations provide general
      advice on the use of all currently clinically available ultrasound contrast
      agents (UCA). They are intended to create standard protocols for the use and
      administration of UCA in liver applications on an international basis and improve
      the management of patients worldwide.

PMID- 23129520
TI  - Endoscopic ultrasound for differential diagnosis of duodenal lesions.
AB  - PURPOSE: Duodenal tumors are rare and require a different management from that of
      esophagogastric neoplasia. The present study retrospectively analyses the
      endoscopic ultrasound (EUS) features of duodenal tumors of both epithelial and
      subepithelial origin. MATERIALS AND METHODS: During a 12 year period, all
      duodenal tumors with histologic confirmation by surgery or biopsy were collected
      including endoscopic and endosonographic images. EUS images were analyzed for
      specific features (echogenicity, wall layer structure and relation, outer
      margins) to possibly distinguish epithelial (polyps and carcinoma versus
      lymphoma) and subepithelial (tumor type) tumors. RESULTS: 53/80 cases had
      histologic confirmation (mean age 53.1 +/- 11.4 years, m:f = 33:20), 31 were
      epithelial (13 adenomas, 12 carcinomas, 6 lymphomas) and 22 subepithelial (11
      GISTs, 7 Brunneromas, 1 lipoma, 3 NETs). EUS did not recognize carcinomas in 2/13
      adenomas. EUS features suggesting carcinoma were loss of wall layers and
      irregular margins. 5/6 lymphomas showed inhomogeneous thickening with layers
      partially recognizable. Tumor type of subepithelial lesions correlated with
      echogenicity: GIST tumors were mostly (62.5 %) hypocheoic with the 3 malignant
      cases being characterized by heterogeneous echopattern with irregular outer
      margins. Of the hyperechoic lesions, lipomas had a homogeneous whitish
      appearance, while NET and Brunneromas were less hyperechoic. In the latter, the
      endoscopic aspect was also helpful for differential diagnosis. Accuracy of
      combined endoscopic/EUS imaging for all duodenal lesions was 84.9 % (45/53). No
      procedural complications occurred among all patients that received EUS
      examinations. CONCLUSION: EUS contributes to the differential diagnosis of
      epithelial lesions known to be malignant; in subepithelial tumors, tissue
      confirmation is still required.

PMID- 23129522
TI  - Total synthesis of (-)-doliculide, structure-activity relationship studies and
      its binding to F-actin.
AB  - Actin, an abundant protein in most eukaryotic cells, is one of the targets in
      cancer research. Recently, a great deal of attention has been paid to the
      synthesis and function of actin-targeting compounds and their use as effective
      molecular probes in chemical biology. In this study, we have developed an
      efficient synthesis of (-)-doliculide, a very potent actin binder with a higher
      cell-membrane permeability than phalloidin. Actin polymerization assays with (-)
      doliculide and two analogues on HeLa and BSC-1 cells, together with a prediction
      of their binding mode to F-actin by unbiased computational docking, show that
      doliculide stabilizes F-actin in a similar way to jasplakinolide and chondramide
      C.

PMID- 23129521
TI  - Intraoperative high frequency ultrasound in intracerebral high-grade tumors.
AB  - PURPOSE: To demonstrate the utility of a new concept of intraoperative use of
      high frequency ultrasound (hfioUS) in maximizing the extent of resection (EOR) of
      intracerebral high-grade tumors. MATERIALS AND METHODS: 22 Patients harboring an
      intracerebral high-grade tumor were retrospectively included in this study (14
      primary tumors, 8 metastasis). 14 of them had a perilesional edema equal or
      greater to lesion volume, 3 had previously received radiotherapy. Following
      macroscopic tumor debulking, the small (11 * 31 mm) L15 - 7io (Philips, Bothell,
      USA) high-frequency probe (7 - 15 MHz) was introduced into the resection cavity
      and its walls were meticulously scanned to search for tumor remnants.
      Postoperative MR scan was evaluated by a board-certified independent
      neuroradiologist, who assessed the EOR. RESULTS: Gross total resection was
      achieved in 21 patients (95.5 %). One patient had a small tumor remnant (6 * 4 *
      3 mm) of a very large (80 * 60 * 74 mm) anaplastic astrocytoma, detected in the
      postoperative MR scan. A permanent postoperative hemiparesis was diagnosed in one
      patient with a metastasis in the motor area, while the other patients recovered
      without permanent neurological deficits from the surgery. CONCLUSION: The hfioUS
      probe allowed in this study a precise detection of the tumor and a detailed
      discrimination between normal, pathological and edematous tissue in all 22 cases.

PMID- 23129523
TI  - Rodent model in caries research.
AB  - The rodent model of dental caries has made fundamental contributions to the
      understanding of the etiology, pathogenesis, and prevention of this disease. In
      conducting animal-based investigations, important details considered essential
      for successful outcome are occasionally overlooked. Adequate number of animals of
      appropriate age should always be included to ensure sufficient statistical power
      to draw valid conclusions. Attention should be paid to litter source as it is
      clear that litter origin may have a profound effect on the outcome. Inclusion of
      additive in diet may also affect eating pattern. A range of special techniques
      are available which can expand the role of animals in exploring the pathogenesis
      of dental caries. The arrival of genetically altered microorganisms along with
      availability of knock-out rodents offers exciting challenges to further explore
      the pathogenesis of this still too common disease.

PMID- 23129524
TI  - Xenophobia and tolerance toward immigrants in adolescence: cross-influence
      processes within friendships.
AB  - To what extent do adolescents and their friends socialize each others' attitudes
      toward immigrants? Can friends' positive attitudes toward immigrants counter
      adolescents' negative attitudes toward immigrants, and do friends' negative
      attitudes decrease adolescents' positive attitudes? These questions were examined
      by following a large (N = 1,472) friendship network of adolescents (49.2 % girls;
      M(age) = 13.31 at first measurement) across three annual measurements. Selection
      and influence processes regarding tolerance and xenophobia were distinguished
      with longitudinal social network analyses, controlling for effects of age,
      gender, and immigrant background. Findings showed that friends' tolerance
      predicted increases in adolescents' tolerance and friends' xenophobia predicted
      increases in adolescents' xenophobia. Moreover, friends' tolerance predicted a
      lower likelihood of adolescents' xenophobia increasing. The current results
      suggest that interventions should distinguish between tolerance and xenophobia,
      as these appear to represent two separate dimensions that are each influenced in
      specific ways by friends' tolerance and xenophobia.

PMID- 23129525
TI  - Arsenic and arsenic species in cultured oyster (Crassostrea gigas and C.
      corteziensis) from coastal lagoons of the SE Gulf of California, Mexico.
AB  - The aim of this study was to evaluate the bioavailability of arsenic (As) through
      cultured oyster Crassostrea gigas and Crassostrea corteziensis from four coastal
      lagoons (SE Gulf of California). Organisms were collected in two seasons (rainy
      and dry season), and they were analyzed for total arsenic and chemical speciation
      of this element. The concentrations of As in oyster soft tissue fluctuated
      between 5.44 and 9.56 MUg/g for rainy season and 6.46 and 8.33 MUg/g for dry
      season (dry weight) in C. gigas. In C. corteziensis, the As concentrations were
      <5 MUg/g for both seasons (dry weight). Arsenic speciation indicated
      arsenobetaine as the major arseno-compound accounting for 43.2-76.3 % of total
      content of As. Lower contributions were obtained for non-extractable As (11.3
      17.5 %) and other molecules such as arsenocholine and methyl-arsonate (<5 %).
      Inorganic arsenic was detectable in only two samples, at concentrations lower
      than <0.1 MUg/g. These As data are the first generated for these mollusks in NW
      Mexico and indicate that C. gigas and C. corteziensis farmed in this area are
      safe for human consumption in terms of arseno-compounds.

PMID- 23129526
TI  - GdCl3 induced Hep G2 cell death through mitochondrial and external death pathways
      without significant elevation of ROS generation.
AB  - Gadolinium (Gd) compounds have important applications as MRI contrast and
      potential anticancer agents. The present study investigated the mechanisms of the
      proapoptotic effect of gadolinium chloride (GdCl(3)) on hepatoblastoma cell line
      (Hep G2) tumor cells. The experimental results indicated that GdCl(3) induced
      apoptosis of Hep G2 at high concentration and with long time incubation; however,
      unlike the actions on normal cell lines, GdCl(3) did not cause any oxidative
      stress on tumor cells. Cytochrome c (Cyt c) and apoptosis inducing factor
      release, Bax translocation, collapse of mitochondria membrane potential, caspase
      3 and 8 activation, and Bid cleavage were observed along with a sustained
      activation of extracellular signal-regulated kinase (ERK) and c-Jun NH2 terminal
      kinase (JNK). Addition of ERK and JNK inhibitor attenuated the effect of GdCl(3)
      induced apoptosis and Cyt c release. All the results suggested a novel mechanism
      that GdCl(3) induced Hep G2 cell death through intrinsic and external death
      pathways without significant elevation of reactive oxygen species generation. The
      present work provided new insight to understand the mechanisms of the biological
      effects of GdCl(3) and implications for the development of anticancer Gd agents.

PMID- 23129527
TI  - Evaluation of the potential of peas (Pisum sativum L.) to be used in selenium
      biofortification programs under Mediterranean conditions.
AB  - Selenium (Se), which has antioxidant, anticancer, and antiviral properties, is an
      essential micronutrient for humans and animals. This micronutrient is found in
      high quantity in legumes. Peas have an ever-increasing importance in Spain, and
      to increase their nutritional value, two foliar Se fertilizers: sodium selenate
      and sodium selenite, at five different rates: 0, 10, 20, 40, 80 g ha(-1), were
      studied during the 2010/2011 crop season on semiarid Mediterranean conditions.
      Sodium selenate was much more effectively taken up by plants compared to sodium
      selenite. There was a strong linear relationship between the total Se content and
      Se rate in both sodium selenate and selenite. For each gram of Se fertilization
      as either sodium selenate or sodium selenite, the increase of total Se
      concentration in the grain was 148 and 19 MUg Se kg(-1) dry weight, respectively.
      Ingestion of 100 g of peas previously fertilized with 10 g of sodium selenate per
      hectare would result in an intake of 179 MUg of Se. This is almost 90 % of the
      daily recommended dose needed to reduce the chance of some cancers and about 179
      % of the minimum concentration required to prevent Se deficiency diseases in
      animals. The pea has shown to have a strong ability to uptake and accumulate Se
      under Mediterranean conditions; therefore, this would make it a very strong
      candidate for inclusion in biofortification programs aiming to increase Se in the
      food chain.

PMID- 23129529
TI  - Fluorescence "turn-on" detection of melamine with aggregation-induced-emission
      active tetraphenylethene.

PMID- 23129528
TI  - The microRNA-9/B-lymphocyte-induced maturation protein-1/IL-2 axis is
      differentially regulated in progressive HIV infection.
AB  - The fine control of T-cell differentiation and its impact on HIV disease states
      is poorly understood. In this study, we demonstrate that B-lymphocyte-induced
      maturation protein-1 (Blimp-1/Prdm1) is highly expressed in CD4(+) T cells from
      chronically HIV-infected (CHI) patients compared to cells from long-term
      nonprogressors or healthy controls. Stimulation through the T-cell receptor in
      the presence of IL-2 induces Blimp-1 protein expression. We show here that Blimp
      1 levels are translationally regulated by microRNA-9 (miR-9). Overexpression of
      miR-9 induces Blimp-1 repression, restoring IL-2 secretion in CD4(+) T cells via
      reduction in the binding of Blimp-1 to the il-2 promoter. In CHI patients where
      IL-2 expression is reduced and there is generalized T-cell dysfunction, we show
      differential expression of both miR-9 and Blimp-1 in CD4(+) cells compared with
      levels in long-term nonprogressors. These data identify a novel miR-9/Blimp-1/IL
      2 axis that is dysregulated in progressive HIV infection.

PMID- 23129530
TI  - Supranuclear gaze palsy in glycine receptor antibody-positive progressive
      encephalomyelitis with rigidity and myoclonus.

PMID- 23129531
TI  - Combination therapy with losartan/hydrochlorothiazide for blood pressure
      reduction and goal attainment in a real-world clinical setting in Japan.
AB  - OBJECTIVE: When physicians prescribe a new antihypertensive drug, they do not
      know the extent of the drug's effect on lowering blood pressure. To resolve this
      dilemma, a Web-based program was constructed for real-time entry and analysis of
      treatment. This observational study evaluated the efficacy of
      losartan/hydrochlorothiazide (Lo/HCTZ) in lowering blood pressure (BP) and
      achieving BP target values. METHODS: Physicians prescribed Lo/HCTZ for patients
      with hypertension who failed to achieve target BP values of < 140/90 mmHg and <
      130/80 mmHg in patients with diabetes or chronic kidney disease, respectively,
      with antihypertensive drugs including an angiotensin receptor blocker. RESULTS:
      From December 2006 to December 2009, the data of 88,254 patients were entered
      into this database, and the data of 24,825 subjects were analyzed. At the first
      visit, a total of 88,254 patients received a first prescription of Lo/HCTZ daily.
      Among these, at the end of the present analysis, 24,825 (28%) outpatients had a
      follow-up visit at 1 month and 20,726 (23%) outpatients had a follow-up visit at
      6 months. The prevalence of hypertensive patients achieving systolic blood
      pressure (SBP) control (< 140 mmHg) increased over time from 6.9% to 54.3% in
      females and 6.1% to 52.3% in males (p < 0.05). At the start of the study, the
      levels of SBP were significantly highest in the eldest patients (>= 75 years)
      followed by the group of 65-75 years and lowest in the youngest patients (<= 64
      years). However, at the end of the study, there were no differences in levels of
      SBP among the three groups. CONCLUSIONS: This Web-based system may provide useful
      information when a new drug is first released into the market. Treatment with
      Lo/HCTZ enabled a substantial proportion of hypertensive patients to achieve the
      recommended goal of < 140/90 mmHg.

PMID- 23129532
TI  - Insight into the origin of the positive effects of imidazolium salt on
      electrocatalytic activity: ionic carbon nanotubes as metal-free electrocatalysts
      for oxygen reduction reaction.
AB  - We report remarkable metal-free electrocatalytic activities of the imidazolium
      salt-functionalized ionic multi-walled carbon nanotubes (IM-f-MWCNTs) in the
      oxygen reduction reaction (ORR). The electrocatalytic activity can be attributed
      to the induced polarization of the pi-electrons of CNTs, thus accelerating
      interfacial electron transfer. The zwitterionic MWCNTs functionalized with
      poly(vinylimidazolium sulfonate) have a more positive surface charge and exhibit
      a better electrocatalytic activity than the poly(vinylbutylimidazolium chloride)
      functionalized MWCNTs. The IM-f-MWCNTs showed better fuel selectivity than the
      commercial Pt/C electrocatalyst.

PMID- 23129533
TI  - HIPEC + EPIC versus HIPEC-alone: differences in major complications following
      cytoreduction surgery for peritoneal malignancy.
AB  - INTRODUCTION: Peritoneal metastases (PM) can be treated with cytoreduction
      surgery (CRS) with intraoperative heated intraperitoneal chemotherapy (HIPEC)
      plus or minus early postoperative intraperitoneal chemotherapy (EPIC). HIPEC +
      EPIC may be associated with more complications than HIPEC alone. METHODS: A
      prospective database of consecutive patients undergoing CRS + HIPEC +/- EPIC at
      the University of Calgary between February 2000 and May 2011 was reviewed.
      Patient, tumor, and perioperative variables included peritoneal cancer index
      (PCI), completeness of cytoreduction (CCR) score, HIPEC +/- EPIC type, and grade
      III/IV complications. RESULTS: 198 patients had a CCR score of 0/1 and received:
      (1) HIPEC mitomycin C + EPIC 5-fluorouracil for 5 days (n = 85; February 2000
      January 2008); or (2) HIPEC oxaliplatin with IV 5-fluorouracil + no EPIC (n =
      113; February 2008-May 2011). Clinicodemographics were similar except PCI was
      higher in the HIPEC-alone group (mean PCI 22 vs. 17; P = 0.02). The rate of grade
      III/IV complications was higher in the HIPEC + EPIC group (44.7% vs. 31.0%; P =
      0.05). On multivariate logistic regression only HIPEC + EPIC and PCI > 26 were
      associated with an increased rate of complications. CONCLUSION: In patients with
      PM, the use of EPIC, in combination with CRS and HIPEC, is associated with an
      increased rate of complications. Surgeons should consider using HIPEC only
      (without EPIC).

PMID- 23129535
TI  - Obstructive sleep apnea and dyslipidemia: pathophysiological mechanisms.

PMID- 23129534
TI  - Antibacterial activity of two chitosan solutions and their effect on rice
      bacterial leaf blight and leaf streak.
AB  - BACKGROUND: Bacterial leaf blight and leaf streak are the two most damaging
      bacterial diseases of rice. However, few bactericidal chemicals are available for
      controlling both diseases. The antibacterial properties of two kinds of chitosan
      with different molecular weights and degrees of N-deacetylation and their effect
      on rice bacterial leaf blight and leaf streak were evaluated. RESULTS: Results
      showed that the two kinds of chitosan solution possess a strong antibacterial
      activity against both rice bacterial pathogens and significantly reduced disease
      incidence and severity by comparison with the control under greenhouse
      conditions. However, the interaction between chitosan and rice pathogens was
      affected by the type and concentration of chitosan, the bacterial species and the
      contact time between chitosan and bacteria. The direct antibacterial activity of
      chitosan may be attributed to both membrane lysis and the destruction of biofilm.
      In addition, both chitosan solutions significantly increased the activities of
      phenylalanine ammonia lyase, peroxidase and polyphenol oxidase in rice seedlings
      following inoculation of two rice pathogens by comparison with the control.
      CONCLUSION: The role of chitosan in protection of rice against bacterial
      pathogens has been shown to involve direct antibacterial activity and indirect
      induced resistance.

PMID- 23129536
TI  - The association between oxidative stress and obstructive sleep apnea syndrome.

PMID- 23129538
TI  - Comparison of methods for quantifying dental wear caused by erosion and abrasion.
AB  - Various methods have been applied to evaluate the effect of erosion and abrasion.
      So, the aim of this study was to check the applicability of stylus profilometry
      (SP), surface hardness (SH) and focus-variation 3D microscopy (FVM) to the
      analysis of human enamel and dentin subjected to erosion/abrasion. The samples
      were randomly allocated into four groups (n = 10): G1-enamel/erosion, G2
      enamel/erosion plus abrasion, G3-dentin/erosion, and G4-dentin/erosion plus
      abrasion. The specimens were selected by their surface hardness, and they were
      subjected to cycles of demineralization (Coca-Cola(r)-60 s) and remineralization
      (artificial saliva-60 min). For groups G2 and G4, the remineralization procedures
      were followed by toothbrushing (150 strokes). The above cycle was repeated 3*/day
      during 5 days. The samples were assessed using SH, SP, and FVM. For each
      substrate, the groups were compared using an unpaired t-test, and Pearson
      correlation coefficients were calculated (alpha = 5%). For enamel, both
      profilometry technique showed greater surface loss when the erosion and abrasion
      processes were combined (P <0.05). The correlation analysis did not reveal any
      relationships among SH, SP, and FVM to G2 and G4. There were significant
      correlation coefficients (-0.70 and -0.67) for the comparisons between the FVM
      and SH methods in enamel and dentin, respectively, in G1 and G3. Choosing the
      ideal technique for the analysis of erosion depends on the type of dental
      substrate. SP was not sufficiently sensitive to measure the effects on dentin of
      erosion or erosion/abrasion. However, SP, FVM and SH were adequate for the
      detection of tissue loss and demineralization in enamel.

PMID- 23129537
TI  - Possible health benefits from reducing occupational magnetic fields.
AB  - BACKGROUND: Magnetic fields (MF) from AC electricity are a Possible Human
      Carcinogen, based on limited epidemiologic evidence from exposures far below
      occupational health limits. METHODS: To help formulate government guidance on
      occupational MF, the cancer cases prevented and the monetary benefits accruing to
      society by reducing workplace exposures were determined. Life-table methods
      produced Disability Adjusted Life Years, which were converted to monetary values.
      RESULTS: Adjusted for probabilities of causality, the expected increase in a
      worker's disability-free life are 0.04 year (2 weeks) from a 1 microtesla (uT) MF
      reduction in average worklife exposure, which is equivalent to $5,100/worker/uT
      in year 2010 U.S. dollars (95% confidence interval $1,000-$9,000/worker/uT).
      Where nine electrosteel workers had 13.8 uT exposures, for example, moving them
      to ambient MFs would provide $600,000 in benefits to society (uncertainty
      interval $0-$1,000,000). CONCLUSIONS: When combined with the costs of controls,
      this analysis provides guidance for precautionary recommendations for managing
      occupational MF exposures.

PMID- 23129539
TI  - Type II ligands as chemical auxiliaries to favor enzymatic transformations by
      P450 2E1.
AB  - The remarkable ability of P450 enzymes to oxidize inactivated C-H bonds and the
      high substrate promiscuity of many P450 isoforms have inspired us and others to
      investigate their use as biocatalysts. Our lab has pioneered a chemical-auxiliary
      approach to control the promiscuity of P450 3A4 and provide product
      predictability. The recent realization that type II ligands are sometimes also
      P450 substrates has prompted the design of a new generation of chemical
      auxiliaries with type II binding properties. This approach takes advantage of the
      high affinity of type II ligands for the active site of these enzymes. Although
      type II ligands typically block P450 activity, we report here that type II
      ligation can be harnessed to achieve just the opposite, that is, to favor
      biocatalysis and afford predictable oxidation of small hydrocarbon substrates
      with P450 2E1. Moreover, the observed predictability was rationalized by
      molecular docking. We hope that this approach might find future use with other
      P450 isoforms and yield complimentary products.

PMID- 23129541
TI  - Automatic intracranial space segmentation for computed tomography brain images.
AB  - Craniofacial disorders are routinely diagnosed using computed tomography imaging.
      Corrective surgery is often performed early in life to restore the skull to a
      more normal shape. In order to quantitatively assess the shape change due to
      surgery, we present an automated method for intracranial space segmentation. The
      method utilizes a two-stage approach which firstly initializes the segmentation
      with a cascade of mathematical morphology operations. This segmentation is then
      refined with a level-set-based approach that ensures that low-contrast
      boundaries, where bone is absent, are completed smoothly. We demonstrate this
      method on a dataset of 43 images and show that the method produces consistent and
      accurate results.

PMID- 23129540
TI  - Fraction of exhaled nitric oxide and wheezing phenotypes in preschool children.
AB  - BACKGROUND: Asthma is a chronic lower airway inflammatory disease. Nitric oxide
      is an inflammatory mediator produced endogenously in the airway. Previous studies
      have demonstrated that the fractional concentration of exhaled nitric oxide
      (FeNO) is increased in asthma. OBJECTIVES: To investigate if FeNO concentrations
      were correlated with wheezing phenotypes in preschool children and to compare the
      FeNO results with airway hyperresponsiveness (AHR) and pulmonary function test
      (PFT) results. METHODS: We performed skin prick tests, methacholine provocation
      tests, PFT, impulse oscillometry bronchodilator response (IOS BDR) tests, and
      FeNO measurements in 372 preschool children between the ages of 4 and 6 years.
      Wheezing phenotypes were defined according to the age of onset and persistency.
      RESULTS: Persistent wheezers had higher FeNO levels than transient wheezers and
      non-wheezers. Among persistent wheezers, those with atopy and AHR had
      significantly higher FeNO levels than those without atopy or AHR. FeNO levels
      were significantly higher in late-onset wheezers than early-onset wheezers and
      non-wheezers. Among late-onset wheezers, those with atopy and AHR had a
      significantly higher FeNO concentration than those without atopy or AHR as well
      as those with either atopy or AHR. However, there were no significant differences
      in AHR, PFT, or IOS BDR between persistent and transient wheezers or between late
      onset wheezers and early-onset wheezers. CONCLUSION: FeNO may be a better marker
      for asthma phenotypes in preschool children than AHR and PFT results.

PMID- 23129542
TI  - Usage and limitations of liquid chromatography-tandem mass spectrometry (LC
      MS/MS) in clinical routine laboratories.
AB  - Technical maturation of liquid chromatography tandem mass spectrometry (LC-MS/MS)
      brought this technology into most tertiary care clinical laboratories worldwide.
      It extended the technological armamentarium of clinical laboratories
      significantly, both in analytical and economical terms. Especially in therapeutic
      drug monitoring, endocrinology, and toxicology, it became an indispensable
      routine tool. Although well-designed LC-MS/MS assays generally outperform
      immunoassays because of increased accuracy, sensitivity, precision, and
      analytical multiplexing capability, they are not free from analytical problems.
      Besides limitations in selectivity due to the occurrence of "isobaric"
      interferences, unpredictable ion yield attenuations, known as "ion suppression
      effect," have to be considered. In addition, most LC-MS/MS methods used in
      clinical laboratories are still laboratory-developed tests ("in-house assays")
      operating on very heterogeneous instrument configurations. Consequently, assay
      heterogeneity and lack of traceability to reference procedures or materials may
      lead to an increased imprecision in proficiency testing as well as inaccurate
      result reporting if basic rules of assay validation and "post marketing"
      surveillance are violated.

PMID- 23129543
TI  - Sleep-disordered breathing in patients with implantable cardioverter
      defibrillator.
AB  - AIMS: To assess the prognostic significance of screening for sleep-disordered
      breathing in patients with implantable cardioverter-defibrillator (ICD) with
      regard to appropriate ICD therapy and total mortality. METHODS AND RESULTS:
      Overnight sleep studies were performed in 204 ICD recipients not known to have
      sleep apnoea and with no history of daytime sleepiness. Sleep-disordered
      breathing was diagnosed in the presence of an apnoea-hypopnea index of five or
      more events per hour. Seventy patients (34%) had no sleep apnoea, 105 patients
      (51%) had central sleep apnoea, and 29 patients (14%) had obstructive sleep
      apnoea. During 38 +/- 26 months follow-up, 80 patients (39%) received appropriate
      ICD therapy for ventricular tachycardia (VT) or ventricular fibrillation (VF),
      and 54 patients (26%) died. On multivariate Cox regression analysis, age, left
      ventricular (LV) end-diastolic diameter, secondary prevention ICD indication, use
      of diuretics, and absence of aldosterone antagonist therapy but not sleep apnoea
      were associated with appropriate ICD therapy for VT or VF. In addition,
      multivariate Cox analysis identified age and LV ejection fraction but not sleep
      apnoea as predictors of total mortality. CONCLUSION: Undiagnosed sleep-disordered
      breathing is common in ICD recipients. The presence and severity of previously
      unknown sleep apnoea in ICD recipients, however, does not appear to be an
      independent predictor of appropriate ICD therapy or morality during follow-up.

PMID- 23129544
TI  - Energy titration strategies with the endoscopic ablation system: lessons from the
      high-dose vs. low-dose laser ablation study.
AB  - AIMS: To assess the effects of low-dose (LD) and high-dose (HD) ablation on acute
      and chronic success in patients with atrial fibrillation (AF). While the concept
      of visually guided pulmonary vein isolation (PVI) has been established little is
      known on energy titration using laser ablation. METHODS AND RESULTS: In 60
      patients with AF, PVI using the endoscopic ablation system (EAS) was performed in
      two groups. Visually guided ablation was carried out after obtaining optimal
      tissue contact with 5.5-8.5 W in the LD group and with >8.5 W in the HD group.
      Acute PVI after a single visually guided circular lesion set was achieved in 89%
      (HD) and 69% (LD), respectively, (P = 0.0004). In 70 and 39% of patients all PVs
      were isolated after a single ablation circle in the HD and LD group,
      respectively, (P = 0.009). After gap ablation all PVs were isolated with the EAS.
      More energy was deployed (6483 +/- 1834 vs. 5306 +/- 2258 Ws; P <= 0.0001) with
      less applications (31.6 +/- 8 vs. 35.2 +/- 15 applications per PV; P = 0.03)
      leading to shorter procedure times (128 +/- 17 vs. 154 +/- 38 min; P = 0.001).
      During median follow-up of 311 days (261-346) recurrence rate was 17 and 40% in
      the HD and LD group, respectively. In both groups one phrenic nerve palsy was
      observed. CONCLUSION: For the first time, it was demonstrated that high ablation
      power affects acute and chronic outcomes. High-dose laser balloon ablation allows
      for an acute PVI rate of 89% solely by visually guided circular ablation and is
      associated with a chronic success rate of 83% after a single procedure.

PMID- 23129545
TI  - Accuracy of the ICD-10 discharge diagnosis for syncope.
AB  - AIMS: Administrative discharge codes are widely used in epidemiology, but the
      specificity and sensitivity of this coding is unknown and must be validated. We
      assessed the validity of the discharge diagnosis of syncope in administrative
      registers and reviewed the etiology of syncope after workup. METHODS AND RESULTS:
      Two samples were investigated. One sample consisted of 5262 randomly selected
      medical patients. The other sample consisted of 750 patients admitted or seen in
      the emergency department (ED) for syncope (ICD-10: R55.9) in three hospitals in
      Denmark. All charts were reviewed for baseline characteristics and to confirm the
      presence/absence of syncope and to compare with the administrative coding. In a
      sample of 600 admitted patients 570 (95%) and of 150 patients from ED 140 (93%)
      had syncope representing the positive predictive values. Median age of the
      population was 69 years (IQR: +/- 14). In the second sample of 5262 randomly
      selected medical patients, 75 (1.4%) had syncope, of which 47 were coded as R55.9
      yielding a sensitivity of 62.7%, a negative predictive value of 99.5%, and a
      specificity of 99.9%. CONCLUSION: ED and hospital discharge diagnostic coding for
      syncope has a positive predictive value of 95% and a sensitivity of 63%.

PMID- 23129546
TI  - Pituitary metastasis presenting as ischemic pituitary apoplexy following heparin
      induced thrombocytopenia.
AB  - Pituitary apoplexy (PA) typically results from infarction or hemorrhage in a
      pituitary adenoma, while PA in nonadenomatous pituitary gland is uncommon.
      Prothrombotic states have never been recognized as precipitating factors for PA.
      The authors report a case of an elderly female who received prophylactic
      fractionated heparin therapy due to sepsis, consequent rhabdomyolysis, and overt
      disseminated intravascular coagulation. On the seventh day of heparin therapy,
      she reported sudden vision loss, ptosis, diplopia, and severe headache. Severe
      thrombocytopenia and positive antibodies to the complex of platelet factor 4 and
      heparin confirmed heparin-induced thrombocytopenia type 2 (HIT). Magnetic
      resonance imaging disclosed a homogenous pituitary tumor mass with pronounced
      sphenoid sinus mucosa thickening and two hypointense zones within the tumor mass
      on contrast-enhanced images consistent with focal ischemic necrosis. The tumor
      was confirmed to be squamous cell carcinoma with no signs of necrosis. Ischemic
      necrosis was found within marginal pituitary tissue. This is the first reported
      case of ischemic PA associated with pituitary metastasis and the first case in
      which HIT triggered PA. Our case demonstrates that prothrombotic states such as
      HIT can precipitate ischemic PA. Pituitary metastasis can present with ischemic
      PA, but radiological features differ from those described in pituitary adenomas.
      Segregated low-signal intensity zones within the tumor mass on postcontrast
      images indicate partial infarction of the tumor, which could be a special feature
      of ischemic PA in pituitary metastasis and has never been described in pituitary
      adenomas. These are all novel findings and might enlighten the pathogenesis of
      PA.

PMID- 23129547
TI  - Albuterol delivery via metered dose inhaler in a spontaneously breathing
      pediatric tracheostomy model.
AB  - RATIONALE: Little data are available regarding efficiency of drug delivery
      devices and techniques despite their widespread use in spontaneously breathing
      tracheostomized patients. We compared patient dose achieved with different
      devices, inhalation techniques, tracheostomy tube sizes and breathing patterns
      using a spontaneously breathing tracheostomized pediatric model. METHODS: A
      tracheostomy model was connected in series to a breathing simulator with a filter
      interposed (patient dose). Breathing patterns of a 16-month-old and a 6- and 12
      year-old child with tracheostomy with internal diameters (mm) of 3.5, 4.5, and
      5.5 were used. Albuterol HFAp MDI was used. Aerotrach Plus, MediBag, Aerochamber
      MV, Aerochamber Mini, and inline adapter with 6-inch tubing were tested. The
      latter 3 devices were also tested with assisted technique. Albuterol was analyzed
      via spectrophotometry. RESULTS: Aerotrach Plus outperformed almost all devices
      tested. Aerochamber MV with unassisted technique was the second best and the
      adapter was the worst. Comparison of efficiency between best and worst performer
      ranged from 3- to 17.2-fold. The 16-month-old breathing pattern and the 3.5 mm
      tracheostomy tube had the lowest patient dose. The use of assisted technique
      decreased patient dose by 18-67% for the 4.5 and 5.5 mm but not for 3.5 mm
      tracheostomy tubes. A median of 7.4% of the nominal dose was deposited in the
      tracheostomy tubes. CONCLUSIONS: Aerotrach Plus and the adapter were the most and
      least efficient devices respectively. Tracheostomy size and breathing pattern
      affected drug delivery. The use of assisted technique reduced aerosol delivery.

PMID- 23129548
TI  - Molecular recognition of zwitterions: enhanced binding and selective recognition
      of miltefosine by a squaramide-based host.

PMID- 23129549
TI  - Increased PD-1 expression on CD4+ and CD8+ T cells is involved in immune evasion
      in gastric cancer.
AB  - BACKGROUND: Co-signaling molecules play an important role in T cells. Programmed
      death-1 (PD-1) is an immunoinhibitory receptor and its overexpression on T cells
      appears to be involved in immune evasion in cancer patients. The present study
      was designed to investigate PD-1 expression on T cells and its relationship with
      immune evasion in gastric cancer patients. METHODS: PD-1 expression on CD4+ and
      CD8+ T cells obtained from peripheral blood mononuclear cells (PBMC), normal
      gastric mucosa, and gastric cancer tissue was evaluated by multicolor flow
      cytometry. RESULTS: PD-1 expression on CD4+ and CD8+ T cells from gastric cancer
      patients was significantly higher than that from normal controls. PD-1 expression
      on CD4+ and CD8+ T cells was related to disease progression. Furthermore, PD-1
      expression on CD4+ and CD8+ T cells from gastric cancer tissue was significantly
      higher than that from normal gastric mucosa and PBMC. PD-1 positive CD4+ and CD8+
      T cells produced significantly less IFN-gamma than PD-1 negative CD4+ and CD8+ T
      cells. CONCLUSIONS: Upregulation of PD-1 on both CD4+ and CD8+ T cells may be, in
      part, responsible for immune evasion in gastric cancer patients.

PMID- 23129550
TI  - A gene-fusion approach to enabling plant cytochromes p450 for biocatalysis.
AB  - Cytochromes P450 from plants have the potential to be valuable catalysts for
      industrial hydroxylation reactions, but their application is hindered by poor
      solubility, the lack of suitable expression systems and the requirement of P450s
      for auxiliary redox-transport proteins for the delivery of reducing equivalents
      from NAD(P)H. In the interests of enabling useful P450 activity from plants, we
      have developed a suite of vectors for the expression of plant P450s as non
      natural genetic fusions with reductase proteins. First, we have fused the P450
      isoflavone synthase (IFS) from Glycine max with the bacterial P450 reductase
      domain (Rhf-RED) from Rhodococcus sp., by using our LICRED vector developed
      previously (F. Sabbadin, R. Hyde, A. Robin, E.-M. Hilgarth, M. Delenne, S.
      Flitsch, N. Turner, G. Grogan, N. C. Bruce, ChemBioChem 2010, 11, 987-994)
      creating the first active bacterial-plant fusion P450 enzyme. We have then
      created a complementary vector, ACRyLIC for the fusion of selected plant P450
      enzymes to the P450 reductase ATR2 from Arabidopsis thaliana. The applicability
      of this vector to the creation of active P450 fusion enzymes was demonstrated
      using both IFS1 and the cinnamate-4-hydroxylase (C4H) from A. thaliana. Overall
      the fusion vector systems will allow the rapid creation of libraries of plant
      P450s with the aim of identifying enzyme activities with possible applications in
      industrial biocatalysis.

PMID- 23129551
TI  - Casting new physicochemical light on the fundamental biological processes in
      single living cells by using Raman microspectroscopy.
AB  - This Personal Account highlights the capabilities of spontaneous Raman
      microspectroscopy for studying fundamental biological processes in a single
      living cell. Raman microspectroscopy provides time- and space-resolved
      vibrational Raman spectra that contain detailed information on the structure and
      dynamics of biomolecules in a cell. By using yeast as a model system, we have
      made great progress in the development of this methodology. The results that we
      have obtained so far are described herein with an emphasis placed on how three
      cellular processes, that is, cell-division, respiration, and cell-death, are
      traced and elucidated with the use of time- and space-resolved structural
      information that is extracted from the Raman spectra. For cell-division,
      compositional- and structural changes of various biomolecules are observed during
      the course of the whole cell cycle. For respiration, the redox state of
      mitochondrial cytochromes, which is inferred from the resonance Raman bands of
      cytochromes, is used to evaluate the respiration activity of a single cell, as
      well as that of isolated mitochondrial particles. Special reference is made to
      the "Raman spectroscopic signature of life", which is a characteristic Raman band
      at 1602 cm(-1) that is found in yeast cells. This signature reflects the cellular
      metabolic activity and may serve as a measure of mitochondrial dysfunction. For
      cell-death, "cross-talk" between the mitochondria and the vacuole in a dying cell
      is suggested.

PMID- 23129552
TI  - Prevalence of work-related dermatitis in the working population.

PMID- 23129553
TI  - Towards a taxonomy of common factors in psychotherapy-results of an expert
      survey.
AB  - BACKGROUND: How change comes about is hotly debated in psychotherapy research.
      One camp considers 'non-specific' or 'common factors', shared by different
      therapy approaches, as essential, whereas researchers of the other camp consider
      specific techniques as the essential ingredients of change. This controversy,
      however, suffers from unclear terminology and logical inconsistencies. The
      Taxonomy Project therefore aims at contributing to the definition and
      conceptualization of common factors of psychotherapy by analyzing their
      differential associations to standard techniques. METHODS: A review identified 22
      common factors discussed in psychotherapy research literature. We conducted a
      survey, in which 68 psychotherapy experts assessed how common factors are
      implemented by specific techniques. Using hierarchical linear models, we
      predicted each common factor by techniques and by experts' age, gender and
      allegiance to a therapy orientation. RESULTS: Common factors differed largely in
      their relevance for technique implementation. Patient engagement, Affective
      experiencing and Therapeutic alliance were judged most relevant. Common factors
      also differed with respect to how well they could be explained by the set of
      techniques. We present detailed profiles of all common factors by the (positively
      or negatively) associated techniques. There were indications of a biased taxonomy
      not covering the embodiment of psychotherapy (expressed by body-centred
      techniques such as progressive muscle relaxation, biofeedback training and
      hypnosis). Likewise, common factors did not adequately represent effective
      psychodynamic and systemic techniques. CONCLUSION: This taxonomic endeavour is a
      step towards a clarification of important core constructs of psychotherapy. KEY
      PRACTITIONER MESSAGE: This article relates standard techniques of psychotherapy
      (well known to practising therapists) to the change factors/change mechanisms
      discussed in psychotherapy theory. It gives a short review of the current debate
      on the mechanisms by which psychotherapy works. We provide detailed profiles of
      change mechanisms and how they may be generated by practice techniques.

PMID- 23129555
TI  - Effect of reductions in biomass fuel exposure on symptoms of sleep apnea in
      children living in the peruvian andes: a preliminary field study.
AB  - BACKGROUND: Multiple studies have evaluated the prevalence of sleep apnea in
      pediatric populations. Although environmental exposures to cigarette smoke (ECS)
      increase the risk of habitual snoring, no studies have thus far examined the
      potential contribution of indoor pollution in children. OBJECTIVE: To determine
      the frequency of symptoms associated with sleep apnea in children exposed to
      traditional wood-burning stoves to open fire, and assess whether symptoms subside
      following implementation of improved less environmentally contaminating stoves.
      METHODS AND MATERIALS: Residents of the communities of Chucllapampa, Sayhuapata,
      and Alparcuna in Cangallo province, department of Ayacucho, Peru were surveyed on
      two occasions within 12 months before and after the installation of an improved
      Inkawasi wood stove. The frequency of symptoms associated with sleep apnea was
      assessed in all children <15 years of age using a previously validated
      questionnaire. RESULTS: Parents of 59 children (62.7% males; mean age 7.76 +/-
      4.2 years) were interviewed representing >97% of the children in those small
      villages. The most common symptoms included nighttime awakenings, habitual
      snoring, repetitive movements during sleep, nasal congestion, and sore throat.
      After implementation of improved stoves in the homes, snoring (52.5% vs. 18.2%, P
      < 0.0001) nasal congestion (33.9% vs. 1.8%, P < 0.0001), behavioral hyperactivity
      (28.8% vs. 3.8%, P < 0.002), nighttime awakenings (42.4% vs. 1.7%, P < 0.0001),
      sore throat (38.2% vs. 5.5% P < 0.0001), breathing through the mouth during the
      day (33.9% vs. 1.8%, P < 0.001), daytime sleepiness (21.1% vs. 1.8%, P < 0.003),
      and falling asleep at school (14.6% vs. 0%, P < 0.03) were all significantly
      improved. CONCLUSIONS: Children exposed to traditional biomass fuel stoves had a
      higher frequency of symptoms related to sleep apnea, which decrease with
      improvements in biomass pollution.

PMID- 23129556
TI  - Editorial.

PMID- 23129554
TI  - Ubiquitin-proteasome system impairment and MPTP-induced oxidative stress in the
      brain of C57BL/6 wild-type and GSTP knockout mice.
AB  - The ubiquitin-proteasome system (UPS) is the primary proteolytic complex
      responsible for the elimination of damaged and misfolded intracellular proteins,
      often formed upon oxidative stress. Parkinson's disease (PD) is
      neuropathologically characterized by selective death of dopaminergic neurons in
      the substantia nigra (SN) and accumulation of intracytoplasmic inclusions of
      aggregated proteins. Along with mitochondrial dysfunction and oxidative stress,
      defects in the UPS have been implicated in PD. Glutathione S-transferase pi
      (GSTP) is a phase II detoxifying enzyme displaying important defensive roles
      against the accumulation of reactive metabolites that potentiate the aggression
      of SN neuronal cells, by regulating several processes including S
      glutathionylation, modulation of glutathione levels and control of kinase
      catalytic activities. In this work we used C57BL/6 wild-type and GSTP knockout
      mice to elucidate the effect of both MPTP and MG132 in the UPS function and to
      clarify if the absence of GSTP alters the response of this pathway to the
      neurotoxin and proteasome inhibitor insults. Our results demonstrate that
      different components of the UPS have different susceptibilities to oxidative
      stress. Importantly, when compared to the wild-type, GSTP knockout mice display
      decreased ubiquitination capacity and overall increased susceptibility to UPS
      damage and inactivation upon MPTP-induced oxidative stress.

PMID- 23129557
TI  - Coping response and survival in breast cancer patients: a new analysis.
AB  - PURPOSE: The purpose of this study was to analyse the impact of coping response
      on survival of breast cancer by using a new method of assessing coping. METHOD:
      Adjustment to cancer was assessed using a revised measure in a large cohort of
      breast cancer patients (N = 578) followed up over a period of 10 years. Impact of
      coping response measured early in the disease process (<4 months from primary
      diagnosis of early-stage breast cancer) was assessed, and survival analyses were
      undertaken including known clinical staging data and cancer treatment details.
      RESULTS: After 5 years of follow-up from primary diagnosis, the effect of prior
      'negative adjustment' was statistically significantly linked to increased risk of
      death and relapse of breast cancer, and for the 10-year analysis, this result
      remained for both risk of death and relapse. There was no statistically
      significant effect on survival of the novel 'positive adjustment' response.
      CONCLUSIONS: Coping with cancer was assessed using a new methodology and is
      linked to an adverse impact of negative adjustment on overall survival. Positive
      adjustment was unrelated to survival. The current study strengthens previous
      evidence that there is a link between survival and coping response. The question
      remains of how coping response might affect physical outcome. It is considered
      that coping response likely impacts survival through the mediating effects on
      lifestyle and health behaviour that may contribute to an adverse prognosis.

PMID- 23129558
TI  - Applying the Stress and 'Strength' Hypothesis to Black women's breast cancer
      screening delays.
AB  - Associations between stress and breast cancer highlight stressful life events as
      barriers to breast cancer screening, increased stress due to a breast cancer
      scare or diagnosis, or the immunosuppressive properties of stress as a risk
      factor for breast cancer occurrence. Little is known, however, about how women's
      reactions to stressful life events impact their breast health trajectory. In this
      study, we explore how reactions to stressors serve as a potential barrier to
      breast cancer screening among Black women. We apply a gender-specific, culturally
      responsive stress-process framework, the Stress and 'Strength' Hypothesis
      ("strength hypothesis"), to understand links between the 'Strong Black Woman
      role' role, Black women's stress reactions and their observed screening delays.
      We conceptualize strength as a culturally prescribed coping style that conditions
      resilience, self-reliance and psychological hardiness as a survival response to
      race-related and gender-related stressors. Using qualitative methods, we
      investigate the potential for this coping mechanism to manifest as extraordinary
      caregiving, emotional suppression and self-care postponement. These
      manifestations may result in limited time for scheduling and attending screening
      appointments, lack of or delay in acknowledgement of breast health symptoms and
      low prioritization of breast care. Limitations and future directions are
      discussed.

PMID- 23129559
TI  - Changes in cerebral blood flow and anxiety associated with an 8-week mindfulness
      programme in women with breast cancer.
AB  - This study employed functional magnetic resonance imaging to evaluate changes in
      cerebral blood flow (CBF) associated with the Mindfulness-based Art Therapy
      (MBAT) programme and correlate such changes to stress and anxiety in women with
      breast cancer. Eighteen breast cancer patients were randomized to the MBAT or
      education control group. The patients received the diagnosis of breast cancer
      between 6 months and 3 years prior to enrollment and were not in active
      treatment. The age of participants ranged from 52 to 77 years. A voxel-based
      analysis was performed to assess differences at rest, during meditation and
      during a stress task. The anxiety sub-scale of the Symptoms Checklist-90-Revised
      was compared with changes in resting CBF before and after the programmes.
      Subjects in the MBAT arm demonstrated significant increases in CBF at rest and
      during meditation in multiple limbic regions, including the left insula, right
      amygdala, right hippocampus and bilateral caudate. Patients in the MBAT programme
      also had a significant correlation between increased CBF in the left caudate and
      decreased anxiety scores. In the MBAT group, responses to a stressful cue
      resulted in reduced activation of the posterior cingulate. The results
      demonstrate that the MBAT programme was associated with significant changes in
      CBF, which correlated with decreased anxiety over an 8-week period.

PMID- 23129560
TI  - Effects of optimism, social support, fighting spirit, cancer worry and internal
      health locus of control on positive affect in cancer survivors: a path analysis.
AB  - The psychological impact of a cancer diagnosis can extend through treatment, well
      into cancer survivorship and can be influenced by a range of psychosocial
      resources. At different stages in this trajectory, optimism is known to affect
      well-being directly. This study focusing upon the potential to flourish after
      cancer, investigates the relationship between optimism and positive affect during
      cancer survivorship together with four possible mediators: social support,
      fighting spirit, internal health locus of control and cancer worry, all of which
      have been shown to be important predictors of well-being in cancer patients.
      Participants (n = 102) from online cancer forums completed standardized
      questionnaires, and path analysis confirmed that optimism had a direct effect on
      positive affect in cancer survivors. Social support and fighting spirit were also
      shown to be significant mediators of this relationship, accounting collectively
      for 50% of the variance in positive affect. Whilst cancer worry and internal
      health locus of control could be predicted from levels of optimism, they did not
      mediate the optimism-positive affect relationship. Efforts to promote optimism
      and thus encourage fighting spirit at diagnosis through treatment may be
      worthwhile interventions, as would ensuring appropriate social support through
      the trajectory.

PMID- 23129561
TI  - Pre-operative stress, anxiety, depression and coping strategies adopted by
      patients experiencing their first or recurrent brain neoplasm: an explorative
      study.
AB  - The main aims of this study were to evaluate the intensity of stress, anxiety and
      depression as well as the effectiveness of coping strategies adopted pre
      operatively in brain neoplasm patients. A descriptive-explorative study design
      was undertaken. During 2008, patients admitted to a large Italian hospital
      neurosurgical unit with their first (n = 21) or recurrent (n = 15) brain
      neoplasm, on the day before their surgical procedure, were consecutively
      recruited into the study. The Perceived Stress Scale, the Hospital Anxiety and
      Depression Scale and the Jalowiec Coping Scale were administered via face-to-face
      interview. Patients with their first occurrence of neoplasm perceived the same
      stress intensity as those with recurrent neoplasm (mean +/- standard deviation:
      14.9 +/- 6.7 versus 17.2 +/- 8.8, p = 0.36). They also reported the same
      likelihood of anxiety at a borderline level (odds ratio (OR) 4.88, 95%CI 0.42 to
      40.97, p = 0.06) and at a clinically relevant level (OR 0.32, 95%CI 0.01 to 5.37,
      p = 0.35) as well as the same likelihood of depression at a borderline level (OR
      1.25, 95%CI 0.20 to 8.40, p = 0.78). Only one case of clinically relevant
      depression emerged among patients at their first diagnosis. Patients at their
      first occurrence, as well as those at recurrence, reported that they adopted
      optimistic coping strategies (mean 2.20, 95%CI 2.01 to 2.38 versus mean 1.96,
      95%CI 1.71 to 2.20) and sought support (mean 1.81, 95%CI 1.58 to 2.05 versus mean
      1.89, 95%CI 1.63 to 2.15). According to the findings of this exploratory study,
      on the pre-operative day, brain neoplasm patients at their first diagnosis and at
      recurrence wish to confront the situation: they adopt optimistic coping
      strategies, they seek support and they wish to take a constructive problem
      solving approach. Knowledge of the intensity of stress, anxiety and depression as
      well as the coping strategies adopted by the patients is important for clinicians
      in their efforts to tailor care to patients' individual needs.

PMID- 23129562
TI  - Tunneling nanotube formation is essential for the regulation of
      osteoclastogenesis.
AB  - Osteoclasts are the multinucleated giant cells formed by cell fusion of
      mononuclear osteoclast precursors. Despite the finding of several membrane
      proteins involving DC-STAMP as regulatory proteins required for fusion among
      osteoclast precursors, cellular and molecular events concerning this process are
      still ambiguous. Here we identified Tunneling Nanotubes (TNTs), long
      intercellular bridges with small diameters, as the essential cellular structure
      for intercellular communication among osteoclast precursors in prior to cell
      fusion. Formation of TNTs was highly associated with osteoclastogenesis and it
      was accompanied with the significant induction of the M-Sec gene, an essential
      gene for TNT formation. M-Sec gene expression was significantly upregulated by
      RANKL-treatment in osteoclast precursor cell line. Blockage of TNT formation by
      Latrunclin B or by M-Sec siRNA significantly suppressed osteoclastogenesis. We
      have detected the rapid intercellular transport of not only the membrane
      phospholipids labeled with DiI but also the DC-STAMP-GFP fusion protein through
      TNTs formed among osteoclast precursors during osteoclastogenesis. Transportation
      of such regulatory molecules through TNTs would be essential for the process of
      the specific cell fusion among osteoclast precursors.

PMID- 23129564
TI  - Salvage abdominoperineal resection for anal cancer following chemoradiation: a
      proposed scoring system for predicting postoperative survival.
AB  - BACKGROUND AND OBJECTIVES: Anal carcinoma is treated primarily by chemoradiation.
      Failure of this treatment requires salvage surgery. The aims of this
      retrospective study were to assess the survival probability after rescue surgery
      and design a pathological risk score (PRS) to predict postoperative outcome.
      METHODS: From 1982 to 2011, the clinical and pathological data of 111 patients
      treated with chemoradiation or radiation alone and abdominoperineal resection
      were reviewed. The Kaplan-Meier method was used to assess overall survival and
      parametric modeling was applied to determine prognostic factors and design a PRS.
      RESULTS: The 2- and 5-year overall survival rates were 60% and 24.5%,
      respectively. The multivariate analysis showed that nodal disease (P < 0.03),
      resection margin (P < 0.001), and perineural and/or lymphovascular invasion (P <
      0.0001) were significantly associated with survival. Patients who presented
      negative values for these three variables were estimated to show a 5-year
      survival rate of 55% compared with 0.03% for patients who presented positive
      values. CONCLUSIONS: Positive surgical margin, the presence of perineural and/or
      lymphovascular invasion and positive nodal involvement were identified as
      significant independent predictors of mortality. The PRS was shown to be highly
      predictive of postoperative outcome.

PMID- 23129563
TI  - Proteome analysis of body fluids for amyotrophic lateral sclerosis biomarker
      discovery.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder
      of motor neurons leading to death of the patients, mostly within 2-5 years after
      disease onset. The pathomechanism of motor neuron degeneration is only partially
      understood and therapeutic strategies based on mechanistic insights are largely
      ineffective. The discovery of reliable biomarkers of disease diagnosis and
      progression is the sine qua non of both the revelation of insights into the ALS
      pathomechanism and the assessment of treatment efficacies. Proteomic approaches
      are an important pillar in ALS biomarker discovery. Cerebrospinal fluid is the
      most promising body fluid for differential proteome analyses, followed by blood
      (serum, plasma), and even urine and saliva. The present study provides an
      overview about reported peptide/protein biomarker candidates that showed
      significantly altered levels in certain body fluids of ALS patients. These
      findings have to be discussed according to proposed pathomechanisms to identify
      modifiers of disease progression and to pave the way for the development of
      potential therapeutic strategies. Furthermore, limitations and advantages of
      proteomic approaches for ALS biomarker discovery in different body fluids and
      reliable validation of biomarker candidates have been addressed.

PMID- 23129565
TI  - Exploring the psychological processes underlying touch: lessons from the
      Alexander Technique.
AB  - The experience of touch is significant; both in its positive implications and in
      how it attracts caution and controversy. Accordingly, physical contact within
      psychological therapy has been shown to improve well-being and the therapeutic
      relationship, yet the majority of therapists never or rarely use touch. This
      research aimed to explore psychological processes underlying touch through the
      Alexander Technique, a psycho-physical technique taught one to one using touch.
      Six individuals who had received the Alexander Technique were interviewed, and
      111 completed surveys. Interview data suggested an incompatibility between touch
      and the spoken word, which was understood through the way touch lacks verbal
      discourses in our society. The largely simplistic and dichotomous verbal
      understanding we have (either only very positive or very negative) could help
      understand some of the societal-level caution surrounding touch. Touch was seen
      also as a nurturing experience by interviewees, which influenced inter-personal
      and intra-personal relational processes. Developmental models were used to frame
      the way touch strengthened the pupil-teacher relationship and the way pupils'
      intra-personal psychological change seemed linked to this relational experience.
      The surveys largely supported these findings, and discussion is made around the
      notable way pupils negatively interpreted the intention of the survey.
      Implications for the use of touch in psychological therapies are discussed, as
      are limitations and ideas for future research. KEY PRACTITIONER MESSAGE: Touch is
      a powerful experience, and physical contact within psychological therapy has been
      shown to improve well-being and the therapeutic relationship, yet the majority of
      therapists never or rarely use touch. The AT is an alternative therapeutic
      approach to psycho-physical well-being that offers an interesting model to study
      the impact of touch. Findings from those that have used the technique reaffirmed
      that touch can improve well-being and can be a powerful force in the 'therapeutic
      relationship'. Accounts drew strong parallels with developmental experiences,
      which may be of particular interest to those working psychodynamically. Findings
      also highlighted the lack of discourses our culture has for touch and how the
      ones we share can be super-imposed onto experiences. This should be kept in mind
      when discussing all types of physical contact with clients. Outcomes from AT
      pupils cannot be generalized to those seeking psychological support; however, the
      findings accentuated the power of holistic working. This is important as we begin
      to understand more around how emotions are held in the body.

PMID- 23129566
TI  - Fundamental paradox of survival determinism: the ur-etiology disease paradigm.
AB  - Following a common practice in medicine, biomedical researches tend to view
      various disease conditions as direct results of preceding, disease-causing
      events. Such events are commonly those that could have been previously detected
      and which have given the history of studies of particular diseases, been
      previously recognized as playing an important role in an onset and/or progression
      of the disease in question. Although such practice is justified from the very
      principles of experimental investigation and scientific observation, it comes
      short of finding the fundamental causes behind these disease conditions. This
      manuscript proposes a different view to the origin of some types of diseases as
      well as some other biological phenomena. Namely, the focus of the concept relates
      to a notion of survival determinism, proposed to have been in the very core of
      evolution of primordial organisms. Thereby, as various disease models are
      discussed in the light of the proposed mechanisms for adaptation, they could be
      seen as relicts of the early evolutionary history of life on Earth.

PMID- 23129567
TI  - Recent advances in the development of Raman spectroscopy for deep non-invasive
      medical diagnosis.
AB  - Raman spectroscopy has recently undergone major advances in the area of deep non
      invasive characterisation of biological tissues. The progress stems from the
      development of spatially offset Raman spectroscopy (SORS) and renaissance of
      transmission Raman spectroscopy permitting the assessment of diffusely scattering
      samples at depths several orders of magnitude deeper than possible with
      conventional Raman spectroscopy. Examples of emerging applications include non
      invasive diagnosis of bone disease, cancer and monitoring of glucose levels. This
      article reviews this fast moving field focusing on recent developments within the
      medical area.

PMID- 23129568
TI  - Management of asthma during pregnancy.
AB  - Asthma is an inflammatory lung condition that is the most common chronic disease
      affecting pregnancy. The changes in pulmonary physiology during pregnancy include
      increased minute ventilation, decreased functional residual capacity, increased
      mucus production, and airway mucosa hyperemia and edema. Pregnancy is also
      associated with a physiological suppression of the immune system. Many studies
      have described the heterogeneous immune system response in women with asthma
      during pregnancy, which partly explains why asthma has been shown to worsen,
      improve, or remain stable in equal proportions of women during pregnancy. Asthma
      may be associated with poor maternal and fetal outcomes. However, better maternal
      and fetal outcomes are observed with better asthma control. Asthma controller
      medications are generally thought to be safe during pregnancy, but limited data
      are available for some of the medicines. Newer medications like omalizumab open
      avenues for the treatment of asthma, but also pose a challenge, as there is
      limited experience with their use. Therefore, a multidisciplinary approach,
      including obstetricians, asthma specialists, and pediatricians should collaborate
      with the patient to carefully weigh the risks and benefits to determine an
      optimal management plan for each individual patient. The aim of this review
      article is to summarize the most recent literature about the immunological
      changes that occur during pregnancy, physiological and clinical implications of
      asthma on pregnancy, and asthma management and medication use in pregnant women.

PMID- 23129569
TI  - Tadalafil as monotherapy and in combination regimens for the treatment of
      pulmonary arterial hypertension.
AB  - The purpose of this review is to evaluate the use of tadalafil as monotherapy and
      in combination regimens for the treatment of pulmonary arterial hypertension
      (PAH). A systematic English language search of the medical literature using
      PubMed was conducted between January 1960 and May 2012 using the search terms
      'tadalafil', 'therapy', 'pulmonary (arterial) hypertension' and 'combination
      therapy'. Special emphasis was given to controlled clinical trials and case
      studies relevant for the use of tadalafil in PAH. The search revealed 113
      relevant publications, 31 of which were clinical trials, 52 were reviews and 12
      were case reports. Of these, 12 were clinical studies in human patients with PAH
      who were treated with tadalafil alone, and seven were clinical studies in human
      patients with PAH who were treated with tadalafil in combination with other
      agents. Only clinical studies in human patients were included. Exclusion criteria
      were monotherapy other than using tadalafil and any combination therapy that
      excluded tadalafil as part of the treatment regimen. Overall, 1353 human subjects
      were studied; 896 were treated with tadalafil alone while 457 subjects were
      treated with tadalafil in coadministration. Tadalafil appears to be an effective
      and a safe treatment option for patients with PAH. It improves clinical status,
      exercise capacity, hemodynamic parameters, compliance issues and quality of life
      and reduces the occurrence of clinical worsening. Tadalafil in combination
      therapy seems to be additive and synergistic in relaxing pulmonary vascular
      muscle cells but more clinical trials on human subjects are warranted.

PMID- 23129570
TI  - Drug-drug interaction between methotrexate and levetiracetam in a child treated
      for acute lymphoblastic leukemia.

PMID- 23129571
TI  - Clinical effectiveness of a patient decision aid to improve decision quality and
      glycaemic control in people with diabetes making treatment choices: a cluster
      randomised controlled trial (PANDAs) in general practice.
AB  - OBJECTIVE: To determine the effectiveness of a patient decision aid (PDA) to
      improve decision quality and glycaemic control in people with diabetes making
      treatment choices using a cluster randomised controlled trial (RCT). DESIGN: A
      cluster RCT. SETTING: 49 general practices in UK randomised into intervention
      (n=25) and control (n=24). PARTICIPANTS: General practices Inclusion criteria: >4
      medical partners; list size >7000; and a diabetes register with >1% of practice
      population. 191 practices assessed for eligibility, and 49 practices randomised
      and completed the study. Patients People with type 2 diabetes mellitus (T2DM)
      taking at least two oral glucose-lowering drugs with maximum tolerated dose with
      a glycosolated haemoglobin (HbA1c) greater than 7.4% (IFCC HbA1c >57 mmol/mol) or
      advised in the preceeding 6 months to add or consider changing to insulin
      therapy. EXCLUSION CRITERIA: currently using insulin therapy; difficulty reading
      or understanding English; difficulty in understanding the purpose of the study;
      visual or cognitive impairment or mentally ill. A total of 182 assessed for
      eligibility, 175 randomised to 95 intervention and 80 controls, and 167
      completion and anlaysis. INTERVENTION: Brief training of clinicians and use of
      PDA with patients in single consultation. PRIMARY OUTCOMES: Decision quality
      (Decisional Conflict Scores, knowledge, realistic expectations and autonomy) and
      glycaemic control (glycosolated haemoglobin, HbA1c). SECONDARY OUTCOMES:
      Knowledge and realistic expectations of the risks and benefits of insulin therapy
      and diabetic complications. RESULTS: Intervention group: lower total Decisional
      Conflict Scores (17.4 vs 25.2, p<0.001); better knowledge (51.6% vs 28.8%,
      p<0.001); realistic expectations (risk of 'hypo', 'weight gain', 'complications';
      81.0% vs 5.2%, 70.5% vs 5.3%, 26.3% vs 5.0% respectively, p<0.001); and were more
      autonomous in decision-making (64.1% vs 42.9%, p=0.012). No significant
      difference in the glycaemic control between the two groups. CONCLUSIONS: Use of
      the PANDAs decision aid reduces decisional conflict, improves knowledge, promotes
      realistic expectations and autonomy in people with diabetes making treatment
      choices in general practice.   ISRCTN TRIALS REGISTER NUMBER:  14842077.

PMID- 23129572
TI  - Blood pressure in different ethnic groups (BP-Eth): a mixed methods study.
AB  - INTRODUCTION: People of South Asian, African-Caribbean and Irish ethnicity are
      known to have worse cardiovascular outcomes than those from the white British
      group. While the reasons underpinning this are complex, the effect of
      hypertension is both significant and modifiable. In recent years, there has been
      increasing interest in and uptake of 'out-of-office' methods for blood pressure
      (BP) monitoring. However, guidance in this area has been largely based on
      research among the white population. This study aims to answer the following
      questions: (1) How often and in what ways does blood pressure (BP) monitoring
      occur and how does this differ between white and the above minority ethnic
      populations. (2) Are the thresholds for diagnosis of hypertension, and treatment
      targets in hypertension comparable for white British and minority ethnic
      populations using different measurement modalities: office blood pressure,
      ambulatory BP monitoring and home monitoring? (3) What preferences for BP
      measurement do people from white and minority ethnic populations have? METHODS
      AND ANALYSIS: A mixed methods approach will be used including the following: (1)
      A postal survey sent to 8000 hypertensive and not-known-to-be-hypertensive people
      from all four ethnic groups will determine current patterns of BP monitoring. (2)
      A validation study will compare BP measurement by ambulatory monitoring with
      office standard measurement, office research measurement and home monitoring in
      200 people from each of the ethnic groups concerned. (3) Focus groups organised
      by ethnicity and gender will gather qualitative data regarding patient
      preferences for and experiences of BP measurement in each of the given
      modalities. The data collected from these phases will be analysed appropriately
      in order to answer the above research questions. ETHICS AND DISSEMINATION:
      Ethical approval has been gained from the Black Country Research Ethics
      Committee: Ref 09/H1202/114. The results of this work will be disseminated via
      journal publication and conference presentation.

PMID- 23129574
TI  - Correction.

PMID- 23129573
TI  - Restless legs syndrome and all-cause mortality in four prospective cohort
      studies.
AB  - OBJECTIVES: To evaluate the association between restless legs syndrome (RLS) and
      all-cause mortality. DESIGN: Four prospective cohort studies. SETTING: The
      Dortmund Health Study (DHS) and the Study of Health in Pomerania (SHIP) from
      Germany. The Women's Health Study (WHS) and the Physicians' Health Study (PHS)
      from the USA. PARTICIPANTS: In DHS: a random sample (n=1 299) from the population
      of Dortmund; in SHIP: a sample (n=4 291) from residents living in West Pomerania
      were drawn by multistage random sampling design; in WHS: female healthcare
      professionals (n=31 370); in PHS: male physicians (n=22 926) MAIN OUTCOME
      MEASURES: All-cause mortality. RESULTS: The prevalence of RLS ranged between 7.4%
      and 11.9% at baseline. During follow-up (ranging between 6 and 11 years) RLS was
      not associated with increased risk of all-cause mortality in any of the four
      cohorts. The multivariable-adjusted HRs (95% CI) for all-cause mortality ranged
      from 0.21 (0.03 to 1.53) to 1.07 (0.93 to 1.23) across the four studies. The HRs
      for all-cause mortality did not differ according to gender. CONCLUSIONS: In these
      four independently conducted large prospective cohort studies from Germany and
      the USA, RLS did not increase the risk of all-cause mortality. These findings do
      not support the hypothesis that RLS is a risk factor for mortality of any cause.

PMID- 23129575
TI  - Coupled external cavity photonic crystal enhanced fluorescence.
AB  - We report a fundamentally new approach to enhance fluorescence in which surface
      adsorbed fluorophore-tagged biomolecules are excited on a photonic crystal
      surface that functions as a narrow bandwidth and tunable mirror of an external
      cavity laser. This scheme leads to ~10* increase in the electromagnetic
      enhancement factor compared to ordinary photonic crystal enhanced fluorescence.
      In our experiments, the cavity automatically tunes its lasing wavelength to the
      resonance wavelength of the photonic crystal, ensuring optimal on-resonance
      coupling even in the presence of variable device parameters and variations in the
      density of surface-adsorbed capture molecules. We achieve ~10(5) * improvement in
      the limit of detection of a fluorophore-tagged protein compared to its detection
      on an unpatterned glass substrate. The enhanced fluorescence signal and easy
      optical alignment make cavity-coupled photonic crystals a viable approach for
      further reducing detection limits of optically-excited light emitters that are
      used in biological assays.

PMID- 23129576
TI  - Inflammatory dilated cardiomyopathy in Abcg5-deficient mice.
AB  - Dilated cardiomyopathy (DCM) in A/J mice homozygous for the spontaneous
      thrombocytopenia and cardiomyopathy (trac) mutation results from a single base
      pair change in the Abcg5 gene. A similar mutation in humans causes sitosterolemia
      with high plant sterol levels, hypercholesterolemia, and early onset
      atherosclerosis. Analyses of CD3+ and Mac-3+ cells and stainable collagen in
      hearts showed inflammation and myocyte degeneration in A/J-trac/trac mice
      beginning postweaning and progressed to marked dilative and fibrosing
      cardiomyopathy by 140 days. Transmission electron microscopy (TEM) demonstrated
      myocyte vacuoles consistent with swollen endoplasmic reticulum (ER). Myocytes
      with cytoplasmic glycogen and irregular actinomyosin filament bundles formed
      mature intercalated disks with normal myocytes suggesting myocyte repair. A/J
      trac/trac mice fed lifelong phytosterol-free diets did not develop
      cardiomyopathy. BALB/cByJ-trac/trac mice had lesser inflammatory infiltrates and
      later onset DCM. BALB/cByJ-trac/trac mice changed from normal to phytosterol-free
      diets had lesser T cell infiltrates but persistent monocyte infiltrates and
      equivalent fibrosis to mice on normal diets. B- and T-cell-deficient BALB/cBy
      Rag1(null) trac/trac mice fed normal diets did not develop inflammatory
      infiltrates or DCM. We conclude that the trac/trac mouse has many features of
      inflammatory DCM and that the reversibility of myocardial T cell infiltration
      provides a novel model for investigating the progression of myocardial fibrosis. 

PMID- 23129578
TI  - Inferior vena cava filter penetration resulting in renal pelvis rupture with
      urinoma formation.
AB  - Inferior vena cava (IVC) filter penetration is common and most often
      asymptomatic. However, penetration may potentially result in a variety of
      complications, including aortic trauma and small bowel perforation. Described is
      a case of IVC filter penetration resulting in renal pelvis perforation with
      urinoma formation.

PMID- 23129577
TI  - Inhibition of mTOR suppresses UVB-induced keratinocyte proliferation and
      survival.
AB  - UV radiation is the major risk factor for developing skin cancer, the most
      prevalent cancer worldwide. Several studies indicate that mTOR signaling is
      activated by UVB and may play an important role in skin tumorigenesis. mTOR
      exists in two functionally and compositionally distinct protein complexes: the
      rapamycin-sensitive mTOR complex 1 (mTORC1) and the rapamycin-resistant mTOR
      complex 2 (mTORC2). The purpose of these studies was to investigate the roles of
      the two mTOR complexes in UVB-mediated proliferation and apoptosis in the skin.
      We used rapamycin, a pharmacologic inhibitor of mTORC1, and an inducible mTOR
      deficient (K5-CreER(T2);mTOR(fl/fl)) mouse model that allows epidermal-specific
      disruption of mTOR following topical treatment with 4-hydroxytamoxifen (4OHT).
      Rapamycin blocked UVB-induced phosphorylation of S6K, the downstream target of
      mTORC1, and significantly reduced UVB-stimulated epidermal proliferation and cell
      cycle progression, but had no effect on cell death. In contrast, mTOR deletion,
      which attenuated UVB-induced phosphorylation of both S6K and the mTORC2 target
      AKT(Ser473), significantly increased apoptosis both in vivo and in keratinocyte
      cultures, in addition to reducing hyperproliferation following UVB irradiation.
      The role of mTORC2 in UVB-induced prosurvival signaling was verified in Rictor(-/
      ) mouse embryo fibroblasts, which lack functional mTORC2 and were more sensitive
      to UVB-induced apoptosis than controls. These studies show that mTORC1 and mTORC2
      play unique but complementary roles in controlling proliferation and apoptosis in
      the skin. Our findings underscore the importance of both mTOR complexes in
      mediating UVB-induced signaling in keratinocytes and provide new insight into the
      pathogenesis of skin cancer.

PMID- 23129579
TI  - Preventing cervical cancer globally.
AB  - Cervical cancer is one of the leading causes of cancer and cancer-related deaths
      among women worldwide. More than 85% of cases and deaths occur in the developing
      world where the availability of effective screening is limited. In this issue of
      the journal, Pierce and colleagues (beginning on page 1273) describe a novel
      technique using a high-resolution microendoscope (HRME) to diagnose cervical
      dysplasia. This perspective reviews the limitations of existing cervical cancer
      screening methods currently in use in low-resource settings and the potential for
      HRME imaging to contribute to cervical cancer prevention in the developing world.

PMID- 23129581
TI  - beta-Actin is predicted as one of the potential targets of miR-145: choose
      internal control gene in verification of microRNA target.

PMID- 23129580
TI  - Lycopene synergistically enhances quinacrine action to inhibit Wnt-TCF signaling
      in breast cancer cells through APC.
AB  - We previously reported that quinacrine (QC) has anticancer activity against
      breast cancer cells. Here, we examine the mechanism of action of QC and its
      ability to inhibit Wnt-TCF signaling in two independent breast cancer cell lines.
      QC altered Wnt-TCF signaling components by increasing the levels of adenomatous
      polyposis coli (APC), DAB2, GSK-3beta and axin and decreasing the levels of beta
      catenin, p-GSK3beta (ser 9) and CK1. QC also reduced the activity of the Wnt
      transcription factor TCF/LEF and its downstream targets cyclin D1 and c-MYC.
      Using a luciferase-based Wnt-TCF transcription factor assay, it was shown that
      APC levels were inversely associated with TCF/LEF activity. Induction of
      apoptosis and DNA damage was observed after treatment with QC, which was
      associated with increased expression of APC. The effects induced by QC depend on
      APC because the inhibition of Wnt-TCF signaling by QC is lost in APC-knockdown
      cells, and consequently, the extent of apoptosis and DNA damage caused by QC is
      reduced compared with parental cells. Because we previously showed that QC
      inhibits topoisomerase, we examined the effect of another topoisomerase
      inhibitor, etoposide, on Wnt signaling. Interestingly, etoposide treatment also
      reduced TCF/LEF activity, beta-catenin and cyclin D1 levels commensurate with
      induction of DNA damage and apoptosis. Lycopene, a plant-derived antioxidant,
      synergistically increased QC activity and inhibited Wnt-TCF signaling in cancer
      cells without affecting the MCF-10A normal breast cell line. Collectively, the
      data suggest that QC-mediated Wnt-TCF signal inhibition depends on APC and that
      the addition of lycopene synergistically increases QC anticancer activity.

PMID- 23129582
TI  - Cervical hematoma following carotid endarterectomy is morbid and preventable: a
      12-year case-controlled review.
AB  - OBJECTIVE: Cervical hematoma (CH) following carotid endarterectomy (CEA) is a
      serious complication. We reviewed 12 years of CEA for CH requiring operative
      evacuation to determine its impact on the patient outcome and relationship to
      perioperative pharmacotherapy. METHODS: A total of 2643 CEAs were reviewed. In
      all, 57 CHs requiring operative evacuation were compared to all the patients for
      general characteristics and with a case-controlled cohort group for pharmacologic
      details. RESULTS: The occurrence of CH was stable from 1994 to 1998 and then
      increased from 1999 to 2003. The CH increased operative mortality, neurologic
      complications, adverse cardiac events, and cranial nerve injury. Combined
      platelet inhibition and dextran alone increased the risk of CH. The CH rate
      dropped by 65% after the observations were reported to the vascular surgeons.
      CONCLUSION: The CH following CEA requiring operative evacuation is associated
      with increased postoperative mortality and cardiac and neurologic morbidity.
      Combined platelet inhibition, use of dextran, and elevated creatinine are
      causally related to CH. Physician awareness and modified pharmacotherapy have
      decreased the problem.

PMID- 23129583
TI  - Identifying the target lesions for 245 laser angioplasty cases and a review of
      the literature.
AB  - OBJECTIVE: To provide a detailed report of our experience with laser atherectomy
      in a large patient population with an extensive follow-up period. METHOD: A
      retrospective chart review was conducted on 222 patients who underwent laser
      atherectomy. RESULTS: Overall primary patency rates at 1 and 3 years were 48% and
      37%, primary-assisted rates were 53% and 40%, and secondary patency rates were
      69% and 51%, respectively. Limb salvage rates were 91% and 83%. The 1- and 3-year
      primary patency rates were significantly different between the native (51% and
      39%) and the in-stent group (20% and 20%; P = .027). There were no differences in
      primary-assisted patency (P = .11), secondary patency (P = .094), and limb
      salvage rates (P= .83) between the 2 groups. CONCLUSIONS: Although the primary
      patency of laser angioplasty was higher in native vessels versus the in-stent
      stenosis, there were no differences in the primary-assisted patency, secondary
      patency, or limb salvage rates between the 2 groups.

PMID- 23129584
TI  - Nimesulide may be more efficient than allopurinol in protecting pancreas from
      acute ischemia/reperfusion injury in an animal model.
AB  - OBJECTIVE: To determine the influence of allopurinol and nimesulide in the
      protection of the pancreas from acute ischemia-reperfusion (I/R) injury.
      MATERIALS AND METHODS: A total of 30 rabbits were divided into 3 groups, group A:
      acute I/R only; group B: allopurinol (30 mg/kg) was administered intravenously 10
      minutes before ischemia; group C: nimesulide (50 mg/kg) was given
      intraperitoneally 20 minutes before ischemia. Neopterin and superoxide dismutase
      (SOD) levels were examined. Pancreatic biopsies were obtained for electron
      microscopy study. RESULTS: The mean neopterin concentrations in group A are 3.56
      +/- 3.41, 7.74 +/- 3.59, and 8.94 +/- 2.86 ng/mL, respectively, in the
      stabilization, ischemia, and reperfusion phases; group B: 3.40 +/- 3.03, 7.45 +/-
      8.89, and 10.64 +/- 7.47 ng/mL; and group C: 3.41 +/- 2.71, 5.67 +/- 2.76, and
      4.34 +/- 2.87 ng/mL. The mean SOD concentrations in group A are 4.25 +/- 1.79,
      4.48 +/- 1.60, and 5.57 +/- 1.15 ng/mL; group B: 4.32 +/- 0.81, 5.08 +/- 1.10,
      and 4.45 +/- 1.31 ng/mL; and group C: 4.10 +/- 0.99, 5.23 +/- 1.60, and 3.72 +/-
      1.30 ng/mL. Histopathology showed the least deterioration in group C. CONCLUSION:
      Nimesulide is more efficient than allopurinol in protecting pancreas from acute
      I/R injury.

PMID- 23129585
TI  - Endovascular retrieval of an inferior vena cava filter with simultaneous caval,
      aortic, and duodenal perforations.
AB  - A 47-year-old female presented to the emergency department complaining of diffuse
      abdominal pain and melena. She previously had a Bard G2X inferior vena cava
      filter placed before undergoing a laparoscopic Roux-en-Y gastric bypass 3 years
      before her current presentation. She had a history of an anastomotic ulcer that
      was treated medically. A repeat endoscopic evaluation revealed no evidence of a
      recent bleed and the ulcer was healed. Computed tomography revealed evidence of
      multiple filter struts penetrating through the caval wall into the duodenum and
      aorta. The filter was successfully removed using an En Snare without
      complications. Reviewing the current literature, open surgical repair has been
      the treatment of choice for similar patient presentations. We present a
      successful case of the endovascular retrieval of an inferior vena cava filter
      with simultaneous caval, aortic, and duodenal penetrations.

PMID- 23129586
TI  - Superior mesenteric arteriovenous fistula: imaging findings and endovascular
      treatment.
AB  - Arteriovenous fistulae (AVF) of the superior mesenteric vasculature are rarely
      encountered. We present a case of an iatrogenic superior mesenteric AVF following
      subtotal colectomy, which was successfully treated with coil embolization. Cross
      sectional imaging and angiographic findings are reviewed along with the options
      for endovascular therapy.

PMID- 23129587
TI  - Neutrophil TRPM2 channels are implicated in the exacerbation of myocardial
      ischaemia/reperfusion injury.
AB  - AIMS: Transient receptor potential melastatin 2 (TRPM2) highly expressed in
      immunocytes is a Ca(2+)-permeable non-selective cation channel activated by
      oxidative stress. Myocardial ischaemia/reperfusion (I/R) injury is characterized
      by acute inflammation associated with the augmentation of oxidative stress. We
      hypothesized that TRPM2 is implicated in the exacerbation of myocardial I/R
      injury. METHODS AND RESULTS: Wild-type (Trpm2(+/+)) and Trpm2 knockout (Trpm2(-/
      )) mice were subjected to ligation of the left main coronary artery followed by
      reperfusion. Myocardial infarction following I/R, but not ischaemia alone, was
      reduced more in Trpm2(-/-)mice than in Trpm2(+/+) mice and cardiac contractile
      functions were also improved in Trpm2(-/-)mice. TRPM2 was highly expressed in the
      polymorphonuclear leucocytes (PMNs) rather than in the heart. The number of
      neutrophils and myeloperoxidase (MPO) activity in the reperfused area following
      ischaemia was lowered in Trpm2(-/-) mice. When Trpm2(+)(/+) or Trpm2(-/-) PMNs
      were administered to the Trpm2(-/-) heart ex vivo through the perfusate or in
      vivo by iv injection, Trpm2(+)(/+) PMNs produced enlargement of the infarct size.
      Following in vitro regional I/R, a pharmacological inhibitor of TRPM2 reduced the
      infarct size. The combination of H(2)O(2) and leukotriene B(4) (LTB(4)) increased
      intracellular Ca(2+) concentration and their adhesion to endothelial cells in
      Trpm2(+)(/+) but not in Trpm2(-/-)PMNs. CONCLUSION: These findings indicate that
      neutrophil TRPM2 is implicated in the exacerbation of myocardial reperfusion
      injury. Accumulation of neutrophils in the reperfused area mediated by TRPM2
      activation is likely to play a crucial role in myocardial I/R injury.

PMID- 23129588
TI  - Chronic depletion of glutathione exacerbates ventricular remodelling and
      dysfunction in the pressure-overloaded heart.
AB  - AIMS: Chronic depletion of myocardial glutathione (GSH) may play a role in
      cardiac remodelling and dysfunction. This study examined the relationship between
      chronic GSH depletion and cardiac failure induced by pressure overload in mice
      lacking the modifier subunit (GCLM) of glutamate-cysteine ligase, the rate
      limiting enzyme for GSH synthesis. In addition, we examined the association
      between idiopathic dilated cardiomyopathy (DCM) in humans and -588C/T
      polymorphism of the GCLM gene, which reduces plasma levels of GSH. METHODS AND
      RESULTS: Pressure overload in mice was created by transverse aortic constriction
      (TAC). Myocardial GSH levels after TAC in GCLM(-/-) mice were 31% of those in
      GCLM(+/+) mice. TAC resulted in greater heart and lung-weight-to-body-weight
      ratios, greater dilation and dysfunction of left ventricle, more extensive
      myocardial fibrosis, and worse survival in GCLM(-/-) than GCLM(+/+) mice.
      Supplementation of GSH diethyl ester reversed the left-ventricular dilation and
      contractile dysfunction and the increased myocardial fibrosis after TAC in GCLM(
      /-) mice. The prevalence of -588T polymorphism of the GCLM gene was significantly
      higher in DCM patients (n = 205) than in age- and sex-matched control subjects (n
      = 253) (36 vs. 19%, respectively, P < 0.001). The -588T polymorphism increased
      the risk of DCM that was independent of age, diabetes, and systolic blood
      pressure (OR 3.13, 95% CI: 2.28-4.44; P < 0.0001). CONCLUSION: Chronic depletion
      of GSH exacerbates remodelling and dysfunction in the pressure-overloaded heart.
      The clinical relevance of this mouse model is supported by a significant
      association between -588T polymorphism of the GCLM gene and patients with DCM.

PMID- 23129589
TI  - Rapid repeat pregnancy among unmarried, African American adolescent parent
      couples.
AB  - This article describes rapid repeat pregnancy (RRP), getting pregnant or giving
      birth again within 24 months of giving birth, in a group of unmarried, low
      income, African American first-time, adolescent parent couples from the
      perspectives of their kinship systems, that is, the adolescent parents and their
      parents or parental figures. RRP has been associated with prematurity, low birth
      weight, inadequate prenatal care, school dropout, increased potential for
      poverty, and prolonged welfare dependence. There were 21 RRPs among 24 kinship
      systems: 9 adolescent males who fathered RRPs with new partners and also reported
      having been denied access to their study babies; 6 adolescent mothers with new
      partners, who also reported intimate partner violence with the study adolescent
      father; and 6 study adolescent parent couples, whose paternal family reported
      doubts about the paternity of the study babies. Adolescent fathers should be
      offered the same child care and contraceptive information routinely offered to
      adolescent mothers.

PMID- 23129591
TI  - Possibility of large volume injection and band focusing in UHPLC.
AB  - New shell-type stationary phases are widely used in fast chromatographic
      measurements. These columns provide more efficient separation, when applied in a
      conventional high-performance liquid chromatography instrument, than columns with
      fully porous particles, and the volume overload of core-shell particles is 60% of
      the value obtained for fully porous particles. Additionally, to achieve adequate
      sensitivity, the injection volume cannot be significantly decreased. This study
      presents a systematic evaluation of the possibilities of large volume injection
      onto columns packed with 2.6 um Kinetex C18 shell particles. The effect of volume
      overload on performance of columns with different lengths (50, 100 and 150 mm) is
      studied. Column efficiency is compared under isocratic, pulse gradient and
      gradient conditions. The application of large volume injection in practice is
      also reported. The most suitable among the tested large volume injection
      techniques was the gradient elution, which was applied to determine amino acid
      enantiomers from fruit juice. 

PMID- 23129590
TI  - Protective effects of low calcium intake and low calcium absorption vitamin D
      receptor genotype in the California Collaborative Prostate Cancer Study.
AB  - BACKGROUND: High calcium intake is consistently associated with increased
      prostate cancer risk in epidemiologic studies. We previously reported that the
      positive association between calcium intake and risk of aggressive prostate
      cancer was modified by the single-nucleotide polymorphism (SNP) in the CDX-2
      binding site of the vitamin D receptor (VDR) gene, among African American men.
      METHODS: We expanded our previous study to include White men, a population with a
      higher calcium intake and a higher prevalence of the low absorption allele. We
      also examined VDR polymorphisms at other loci unrelated to calcium absorption.
      The study included 1,857 prostate cancer cases (1,140 with advanced stage at
      diagnosis, 717 with localized stage) and 1,096 controls. OR were estimated using
      conditional logistic regression. RESULTS: Among both Blacks and Whites, we
      observed a threshold for calcium intake (604 mg/d) below which prostate cancer
      risk declined sharply. Low calcium intake was most strongly associated with
      decreased risk among men with the VDR Cdx2 low calcium absorption genotype (P for
      interaction = 0.001 and P = 0.06 for Whites and African Americans, respectively).
      Among all men with this genotype, those in the lowest quartile of calcium intake
      (<=604 mg/d) had a 50% reduction in risk as compared with those in the upper
      three quartiles [OR = 0.49; 95% confidence interval (CI), 0.36-0.67]. The
      association between calcium intake and prostate cancer risk was not modified by
      genotype at other VDR loci. CONCLUSIONS: Our findings support the hypothesis that
      genetic determinants of calcium absorption influence prostate cancer risk.
      IMPACT: The differences between African Americans and Whites in calcium
      absorption and dietary calcium intake may contribute to racial disparities in
      prostate cancer incidence and mortality rates.

PMID- 23129592
TI  - Approach to the child with prader-willi syndrome.

PMID- 23129593
TI  - The skeleton and the sympathetic nervous system: it's about time!

PMID- 23129594
TI  - The new world of clinical genomics.

PMID- 23129595
TI  - Raising serum gastrin to improve glycemic control in (type 2) diabetes: another
      limb of the enteroinsular axis?

PMID- 23129600
TI  - Detecting and treating thyroid nodules and cancer before, during, and after
      pregnancy: a patient's guide.

PMID- 23129601
TI  - Effects of interleukin-1beta inhibition with canakinumab on hemoglobin A1c,
      lipids, C-reactive protein, interleukin-6, and fibrinogen: a phase IIb
      randomized, placebo-controlled trial.
AB  - BACKGROUND: To test formally the inflammatory hypothesis of atherothrombosis, an
      agent is needed that reduces inflammatory biomarkers such as C-reactive protein,
      interleukin-6, and fibrinogen but that does not have major effects on lipid
      pathways associated with disease progression. METHODS AND RESULTS: We conducted a
      double-blind, multinational phase IIb trial of 556 men and women with well
      controlled diabetes mellitus and high cardiovascular risk who were randomly
      allocated to subcutaneous placebo or to subcutaneous canakinumab at doses of 5,
      15, 50, or 150 mg monthly and followed over 4 months. Compared with placebo,
      canakinumab had modest but nonsignificant effects on the change in hemoglobin
      A1c, glucose, and insulin levels. No effects were seen for low-density
      lipoprotein cholesterol, high-density lipoprotein cholesterol, or non-high
      density lipoprotein cholesterol, although triglyceride levels increased ~10% in
      the 50-mg (P=0.02) and 150-mg (P=0.03) groups. By contrast, the median reductions
      in C-reactive protein at 4 months were 36.4%, 53.0%, 64.6%, and 58.7% for the 5-,
      15-, 50-, and 150-mg canakinumab doses, respectively, compared with 4.7% for
      placebo (all P values <=0.02). Similarly, the median reductions in interleukin-6
      at 4 months across the canakinumab dose range tested were 23.9%, 32.5%, 47.9%,
      and 44.5%, respectively, compared with 2.9% for placebo (all P<=0.008), and the
      median reductions in fibrinogen at 4 months were 4.9%, 11.7%, 18.5%, and 14.8%,
      respectively, compared with 0.4% for placebo (all P values <=0.0001). Effects
      were observed in women and men. Clinical adverse events were similar in the
      canakinumab and placebo groups. CONCLUSIONS: Canakinumab, a human monoclonal
      antibody that neutralizes interleukin-1beta, significantly reduces inflammation
      without major effect on low-density lipoprotein cholesterol or high-density
      lipoprotein cholesterol. These phase II trial data support the use of canakinumab
      as a potential therapeutic method to test directly the inflammatory hypothesis of
      atherosclerosis.

PMID- 23129602
TI  - Low-density lipoprotein cholesterol-lowering effects of AMG 145, a monoclonal
      antibody to proprotein convertase subtilisin/kexin type 9 serine protease in
      patients with heterozygous familial hypercholesterolemia: the Reduction of LDL-C
      with PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder
      (RUTHERFORD) randomized trial.
AB  - BACKGROUND: Despite statin treatment, many patients with heterozygous familial
      hypercholesterolemia do not reach desired low-density lipoprotein cholesterol
      (LDL-C) targets. AMG 145, a fully human monoclonal antibody against proprotein
      convertase subtilisin/kexin type 9 (PCSK9) serine protease, demonstrated
      significant reductions in LDL-C in phase 1 studies. This phase 2, multicenter,
      double-blind, randomized, placebo-controlled, dose-ranging study evaluated the
      efficacy and safety of AMG 145 in heterozygous familial hypercholesterolemia
      patients. METHODS AND RESULTS: Patients with heterozygous familial
      hypercholesterolemia diagnosed by Simon Broome criteria with LDL-C >=2.6 mmol/L
      (100 mg/dL) despite statin therapy with or without ezetimibe were randomized
      1:1:1 to AMG 145 350 mg, AMG 145 420 mg, or placebo-administered subcutaneously
      every 4 weeks. The primary end point was percentage change from baseline in LDL-C
      at week 12. Of 168 patients randomized, 167 received investigational product and
      were included in the full analysis set (mean [SD] age, 50 [13] years; 47% female;
      89% white; mean [SD] baseline LDL-C, 4.0 [1.1] mmol/L (156 [42] mg/dL)). At week
      12, LDL-C reduction measured by preparative ultracentrifugation (least squares
      mean [standard error (SE)]) was 43 (3)% and 55 (3)% with AMG 145 350 mg and 420
      mg, respectively, compared with 1 (3)% increase with placebo (P<0.001 for both
      dose groups). Serious adverse events (not considered treatment-related) occurred
      in 2 patients on AMG 145. CONCLUSIONS: AMG 145 administered every 4 weeks yielded
      rapid and substantial reductions in LDL-C in heterozygous familial
      hypercholesterolemia patients despite intensive statin use, with or without
      ezetimibe, with minimal adverse events and good tolerability. CLINICAL TRIAL
      REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01375751.

PMID- 23129603
TI  - A case study of the characteristics of municipal solid waste in Asturias (Spain):
      influence of season and source.
AB  - In the present research study, the weight composition, physical-chemical
      composition and net calorific values of unsorted municipal solid waste (MSW)
      generated by a population of around 1,080,000 inhabitants in a region of northern
      Spain were determined. The unsorted MSW was composed of 38.1% organic fraction
      and 42.3% combustible fraction, with paper/cardboard constituting the most
      important part of the latter fraction (20.6%). The high content of textiles
      (10.9%) is worth noting, being practically equal to the content in plastics. The
      unsorted fractions present an average moisture content of 28.5% and an ash
      content of 29.4% (dry basis). The average lower heating value (LHV) is 10,744 kJ
      kg(-1). Likewise, variations in regard to the season of the year and the source
      of the waste were taken into consideration. A new correlation is proposed for
      estimating the LHV as a function of the physical composition of the waste.

PMID- 23129604
TI  - Municipal solid waste management for total resource recycling: a case study on
      Haulien County in Taiwan.
AB  - This work presents the enforcement performance of recent Haulien County, Taiwan
      municipal solid waste (MSW) recycling management programs. These programs
      include: Mandatory Refuse Sorting and Recycling, Diverse Bulk Waste Reuse, Pay-as
      you-Discharge, Total Food Waste Recycling, Restricted Use on Plastic Shopping
      Bags & Plastic Tableware, Recycling Fund Management, and Ash Reuse. These
      programs provide incentives to reduce the MSW quantity growth rate. It was found
      that the recycled material fraction of MSW generated in 2001 was from 6.8%, but
      was 32.4% in 2010 and will increase stably by 2-5% yearly in the near future.
      Survey data for the last few years show that only 2.68% (based on total MSW
      generated) of food waste was collected in 2001. However, food waste was up to
      9.7% in 2010 after the Total Food Waste Recycling program was implemented. The
      reutilization rate of bottom ash was 20% in 2005 and up to 65% in 2010 owing to
      Ash Reuse Program enforcement. A quantified index, the Total Recycle Index, was
      proposed to evaluate MSW management program performance. The demonstrated county
      will move toward a zero waste society in 2015 if the Total Recycle Index
      approaches 1.00. Exact management with available programs can lead to slow
      growing waste volume and recovery of all MSW.

PMID- 23129605
TI  - Constrained recycling: a framework to reduce landfilling in developing countries.
AB  - This article presents a model that integrates three branches of research: (i)
      economics of solid waste that assesses consumer's willingness to recycle and to
      pay for disposal; (ii) economics of solid waste that compares private and social
      costs of final disposal and recycling; and (iii) theories on personal attitudes
      and social influence. The model identifies two arenas where decisions are made:
      upstream arena, where residents are decision-makers, and downstream arena, where
      municipal authorities are decision-makers, and graphically proposes interactions
      between disposal and recycling, as well as the concept of 'constrained recycling'
      (an alternative to optimal recycling) to guide policy design. It finally
      concludes that formative instruments, such as environmental education and
      benchmarks, should be combined with economic instruments, such as subsidies, to
      move constraints on source separation and recycling in the context of developing
      countries.

PMID- 23129606
TI  - Management strategies on the industrialization road of state-of-the-art
      technologies for e-waste recycling: the case study of electrostatic separation--a
      review.
AB  - Electronic waste (e-waste) management is pressing as global production has
      increased significantly in the past few years and is rising continuously at a
      fast rate. Many countries are facing hazardous e-waste mountains, most of which
      are disposed of by backyard recyclers, creating serious threats to public health
      and ecosystems. Industrialization of state-of-the-art recycling technologies is
      imperative to enhance the comprehensive utilization of resources and to protect
      the environment. This article aims to provide an overview of management
      strategies solving the crucial problems during the process of industrialization.
      A typical case study of electrostatic separation for recycling waste printed
      circuit boards was discussed in terms of parameters optimization, materials flow
      control, noise assessment, risk assessment, economic evaluation and social
      benefits analysis. The comprehensive view provided by the review could be helpful
      to the progress of the e-waste recycling industry.

PMID- 23129607
TI  - Landfills as sinks for (hazardous) substances.
AB  - The primary goal of waste regulations is to protect human health and the
      environment. This requires the removal from the material cycle of those materials
      that cannot be processed without harm. Policies to promote recycling hold a risk
      that pollutants are dispersed. Materials have an environmental impact during
      their entire life cycle from extraction through production, consumption and
      recycling to disposal. Essentially there are only two routes for pollutants that
      cannot be rendered harmless: storage in sinks or dispersion into the environment.
      Many sinks do not contain substances absolutely, but result in slow dispersion.
      Dispersion leads to exposure and impact to human health and the environment. It
      is therefore important to assess the impact of the release to the environment.
      Based on various sources this paper discusses important material flows and their
      potential impact. This is compared with the intentions and achievements of
      European environmental and resource policy. The polluter pays principle is being
      implemented in Europe, but lags behind implementation of waste management
      regulations. As long as producers are allowed to add hazardous substances to
      their products and don't take their products back, it is in society's best
      interest to carefully consider whether recycling or storage in a sink is the
      better solution. This requires further development of life-cycle assessment tools
      and harmonization of regulations. In many cases the sink is unavoidable.
      Landfills as sinks will be needed in the future. Fail-safe design and
      construction as well as sustainable management of landfills must be further
      developed.

PMID- 23129608
TI  - Effective solutions for monitoring the electrostatic separation of metal and
      plastic granular waste from electric and electronic equipment.
AB  - The variability of the quantity and purity of the recovered materials is a
      serious drawback for the application of electrostatic separation technologies to
      the recycling of granular wastes. In a series of previous articles we have
      pointed out how capability and classic control chart concepts could be employed
      for better mastering the outcome of such processes. In the present work, the
      multiple exponentially weighted moving average (MEWMA) control chart is
      introduced and shown to be more effective than the Hotelling T2 chart for
      monitoring slow varying changes in the electrostatic separation of granular
      mixtures originating from electric and electronic equipment waste. The operation
      of the industrial process was simulated by using a laboratory roll-type
      electrostatic separator and granular samples resulting from shredded electric
      cable wastes. The 25 tests carried out during the observation phase enabled the
      calculation of the upper and lower control limits for the two control charts
      considered in the present study. The 11 additional tests that simulated the
      monitoring phase pointed out that the MEWMA chart is more effective than
      Hotelling's T(2) chart in detecting slow varying changes in the outcome of a
      process. As the reverse is true in the case of abrupt alterations of monitored
      process performances, simultaneous usage of the two control charts is strongly
      recommended. While this study focused on a specific electrostatic separation
      process, using the MEWMA chart together with the well known Hotelling's T(2)
      chart should be applicable to the statistical control of other complex processes
      in the field of waste processing.

PMID- 23129609
TI  - Changes in greenhouse gas balance and resource demand of biogas plants in
      southern Germany after a period of three years.
AB  - For five agricultural biogas plants with a high share of energy crops in the
      input material, a detailed balance of greenhouse gas emissions (GHG) and
      cumulated energy demand (CED) was calculated for the years 2007 and 2010. The
      results vary considerably between plants and over time. In 2010 compared with
      2007, all of the five biogas plants reduced their impact on climate change and
      four of them also reduced their consumption of fossil energy. The strongest
      influence was from the enhanced utilization of surplus heat energy, whereas
      variations of environmental impact due to direct emissions from the biogas plants
      were less distinctive. Compared with a reference system based on fossil
      resources, electricity production in the biogas plants avoided GHG emissions of
      603 g to 940 g carbon dioxide equivalents (CO2-eq)*kilowatt hours electrical
      energy (kWhel (-1)) and saved 2.48 to 3.23 kilowatt hours primary energy from
      fossil energy carriers (kWhfossil)*kWhel (-1) CED (results for 2010).

PMID- 23129610
TI  - Carbon abatement via treating the solid waste from the Australian olive industry
      in mobile pyrolysis units: LCA with uncertainty analysis.
AB  - The olive oil industry in Australia has been growing at a rapid rate over the
      past decade. It is forecast to continue growing due to the steady increase in
      demand for olive oil and olive products in the local and regional market.
      However, the olive oil extraction process generates large amounts of solid waste
      called olive husk which is currently underutilized. This paper uses life-cycle
      methodology to analyse the carbon emission reduction potential of utilizing olive
      husk as a feedstock in a mobile pyrolysis unit. Four scenarios, based on
      different combinations of pyrolysis technologies (slow versus fast) and end-use
      of products (land application versus energy utilization), are constructed. The
      performance of each scenario under conditions of uncertainty was also
      investigated. The results show that all scenarios result in significant carbon
      emission abatement. Processing olive husk in mobile fast pyrolysis units and the
      utilization of bio-oil and biochar as substitutes for heavy fuel oil and coal is
      likely to realize a carbon offset greater than 32.3 Gg CO2-eq annually in 90% of
      the time. Likewise, more than 3.2 Gg-C (11.8 Gg CO2-eq) per year could be
      sequestered in the soil in the form of fixed carbon if slow mobile pyrolysis
      units were used to produce biochar.

PMID- 23129611
TI  - Cancer resistance in the blind mole rat is mediated by concerted necrotic cell
      death mechanism.
AB  - Blind mole rats Spalax (BMR) are small subterranean rodents common in the Middle
      East. BMR is distinguished by its adaptations to life underground, remarkable
      longevity (with a maximum documented lifespan of 21 y), and resistance to cancer.
      Spontaneous tumors have never been observed in spalacids. To understand the
      mechanisms responsible for this resistance, we examined the growth of BMR
      fibroblasts in vitro of the species Spalax judaei and Spalax golani. BMR cells
      proliferated actively for 7-20 population doublings, after which the cells began
      secreting IFN-beta, and the cultures underwent massive necrotic cell death within
      3 d. The necrotic cell death phenomenon was independent of culture conditions or
      telomere shortening. Interestingly, this cell behavior was distinct from that
      observed in another long-lived and cancer-resistant African mole rat,
      Heterocephalus glaber, the naked mole rat in which cells display hypersensitivity
      to contact inhibition. Sequestration of p53 and Rb proteins using SV40 large T
      antigen completely rescued necrotic cell death. Our results suggest that cancer
      resistance of BMR is conferred by massive necrotic response to overproliferation
      mediated by p53 and Rb pathways, and triggered by the release of IFN-beta. Thus,
      we have identified a unique mechanism that contributes to cancer resistance of
      this subterranean mammal extremely adapted to life underground.

PMID- 23129612
TI  - Phleboviruses encapsidate their genomes by sequestering RNA bases.
AB  - Rift Valley fever and Toscana viruses are human pathogens for which no effective
      therapeutics exist. These and other phleboviruses have segmented negative-sense
      RNA genomes that are sequestered by a nucleocapsid protein (N) to form
      ribonucleoprotein (RNP) complexes of irregular, asymmetric structure, previously
      uncharacterized at high resolution. N binds nonspecifically to single-stranded
      RNA with nanomolar affinity. Crystal structures of Rift Valley fever virus N-RNA
      complexes reconstituted with defined RNAs of different length capture tetrameric,
      pentameric and hexameric N-RNA multimers. All N-N subunit contacts are mediated
      by a highly flexible alpha-helical arm. Arm movement gives rise to the three
      multimers in the crystal structures and also explains the asymmetric architecture
      of the RNP. Despite the flexible association of subunits, the crystal structures
      reveal an invariant, monomeric RNP building block, consisting of the core of one
      N subunit, the arm of a neighboring N, and four RNA nucleotides with the flanking
      phosphates. Up to three additional RNA nucleotides bind between subunits. The
      monomeric building block is matched in size to the repeating unit in viral RNP,
      as visualized by electron microscopy. N sequesters four RNA bases in a narrow
      hydrophobic binding slot and has polar contacts only with the sugar-phosphate
      backbone, which faces the solvent. All RNA bases, whether in the binding slot or
      in the subunit interface, face the protein in a manner that is incompatible with
      base pairing or with "reading" by the viral polymerase.

PMID- 23129613
TI  - Protein tyrosine phosphatase 1B is a key regulator of IFNAR1 endocytosis and a
      target for antiviral therapies.
AB  - Type 1 interferons (IFN1) elicit antiviral defenses by activating the cognate
      receptor composed of IFN-alpha/beta receptor chain 1 (IFNAR1) and IFNAR2. Down
      regulation of this receptor occurs through IFN1-stimulated IFNAR1 ubiquitination,
      which exposes a Y466-based linear endocytic motif within IFNAR1 to recruitment of
      the adaptin protein-2 complex (AP2) and ensuing receptor endocytosis.
      Paradoxically, IFN1-induced Janus kinase-mediated phosphorylation of Y466 is
      expected to decrease its affinity for AP2 and to inhibit the endocytic rate. To
      explain how IFN1 promotes Y466 phosphorylation yet stimulates IFNAR1
      internalization, we proposed that the activity of a protein tyrosine phosphatase
      (PTP) is required to enable both events by dephosphorylating Y466. An RNAi-based
      screen identified PTP1B as a specific regulator of IFNAR1 endocytosis stimulated
      by IFN1, but not by ligand-independent inducers of IFNAR1 ubiquitination. PTP1B
      is a promising target for treatment of obesity and diabetes; numerous research
      programs are aimed at identification and characterization of clinically relevant
      inhibitors of PTP1B. PTP1B is capable of binding and dephosphorylating IFNAR1.
      Genetic or pharmacologic modulation of PTP1B activity regulated IFN1 signaling in
      a manner dependent on the integrity of Y466 within IFNAR1 in human cells. These
      effects were less evident in mouse cells whose IFNAR1 lacks an analogous motif.
      PTP1B inhibitors robustly augmented the antiviral effects of IFN1 against
      vesicular stomatitis and hepatitis C viruses in human cells and proved beneficial
      in feline stomatitis patients. The clinical significance of these findings in the
      context of using PTP1B inhibitors to increase the therapeutic efficacy of IFN
      against viral infections is discussed.

PMID- 23129614
TI  - Cripto regulates skeletal muscle regeneration and modulates satellite cell
      determination by antagonizing myostatin.
AB  - Skeletal muscle regeneration mainly depends on satellite cells, a population of
      resident muscle stem cells. However, our understanding of the molecular
      mechanisms underlying satellite cell activation is still largely undefined. Here,
      we show that Cripto, a regulator of early embryogenesis, is a novel regulator of
      muscle regeneration and satellite cell progression toward the myogenic lineage.
      Conditional inactivation of cripto in adult satellite cells compromises skeletal
      muscle regeneration, whereas gain of function of Cripto accelerates regeneration,
      leading to muscle hypertrophy. Moreover, we provide evidence that Cripto
      modulates myogenic cell determination and promotes proliferation by antagonizing
      the TGF-beta ligand myostatin. Our data provide unique insights into the
      molecular and cellular basis of Cripto activity in skeletal muscle regeneration
      and raise previously undescribed implications for stem cell biology and
      regenerative medicine.

PMID- 23129616
TI  - Arrested demixing opens route to bigels.
AB  - Understanding and, ultimately, controlling the properties of amorphous materials
      is one of the key goals of material science. Among the different amorphous
      structures, a very important role is played by colloidal gels. It has been only
      recently understood that colloidal gels are the result of the interplay between
      phase separation and arrest. When short-ranged attractive colloids are quenched
      into the phase-separating region, density fluctuations are arrested and this
      results in ramified amorphous space-spanning structures that are capable of
      sustaining mechanical stress. We present a mechanism of aggregation through
      arrested demixing in binary colloidal mixtures, which leads to the formation of a
      yet unexplored class of materials--bigels. This material is obtained by tuning
      interspecies interactions. Using a computer model, we investigate the phase
      behavior and the structural properties of these bigels. We show the topological
      similarities and the geometrical differences between these binary,
      interpenetrating, arrested structures and their well-known monodisperse
      counterparts, colloidal gels. Our findings are supported by confocal microscopy
      experiments performed on mixtures of DNA-coated colloids. The mechanism of bigel
      formation is a generalization of arrested phase separation and is therefore
      universal.

PMID- 23129615
TI  - Bone morphogenetic protein- and mating-dependent secretory cell growth and
      migration in the Drosophila accessory gland.
AB  - The paired male accessory glands of Drosophila melanogaster enhance sperm
      function, stimulate egg production, and reduce female receptivity to other males
      by releasing a complex mixture of glycoproteins from a secretory epithelium into
      seminal fluid. A small subpopulation of about 40 specialized secretory cells,
      called secondary cells, resides at the distal tip of each gland. We show that
      these cells grow via mechanisms promoted by mating. If aging males mate
      repeatedly, a subset of these cells delaminates from and migrates along the
      apical surface of the glandular epithelium toward the proximal end of the gland.
      Remarkably, these secretory cells can transfer to females with sperm during
      mating. The frequency of this event increases with age, so that more than 50% of
      triple-mated, 18-d-old males transfer secondary cells to females. Bone
      morphogenetic protein signaling specifically in secondary cells is needed to
      drive all of these processes and is required for the accessory gland to produce
      its normal effects on female postmating behavior in multiply mated males. We
      conclude that secondary cells are secretory cells with unusual migratory
      properties that can allow them to be transferred to females, and that these
      properties are a consequence of signaling that is required for secondary cells to
      maintain their normal reproductive functions as males age and mate.

PMID- 23129617
TI  - Ubiquitin ligase RNF167 regulates AMPA receptor-mediated synaptic transmission.
AB  - AMPA receptors (AMPARs) mediate the majority of fast excitatory
      neurotransmission, and their density at postsynaptic sites determines synaptic
      strength. Ubiquitination is a posttranslational modification that dynamically
      regulates the synaptic expression of many proteins. However, very few of the
      ubiquitinating enzymes implicated in the process have been identified. In a
      screen to identify transmembrane RING domain-containing E3 ubiquitin ligases that
      regulate surface expression of AMPARs, we identified RNF167. Predominantly
      lysosomal, a subpopulation of RNF167 is located on the surface of cultured
      neurons. Using a RING mutant RNF167 or a specific shRNA to eliminate endogenous
      RNF167, we demonstrate that AMPAR surface expression increases in hippocampal
      neurons with disrupted RNF167 activity and that RNF167 is involved in activity
      dependent ubiquitination of AMPARs. In addition, RNF167 regulates synaptic AMPAR
      currents, whereas synaptic NMDAR currents are unaffected. Therefore, our study
      identifies RNF167 as a selective regulator of AMPAR-mediated neurotransmission
      and expands our understanding of how ubiquitination dynamically regulates
      excitatory synapses.

PMID- 23129618
TI  - Generalized entropies and logarithms and their duality relations.
AB  - For statistical systems that violate one of the four Shannon-Khinchin axioms,
      entropy takes a more general form than the Boltzmann-Gibbs entropy. The framework
      of superstatistics allows one to formulate a maximum entropy principle with these
      generalized entropies, making them useful for understanding distribution
      functions of non-Markovian or nonergodic complex systems. For such systems where
      the composability axiom is violated there exist only two ways to implement the
      maximum entropy principle, one using escort probabilities, the other not. The two
      ways are connected through a duality. Here we show that this duality fixes a
      unique escort probability, which allows us to derive a complete theory of the
      generalized logarithms that naturally arise from the violation of this axiom. We
      then show how the functional forms of these generalized logarithms are related to
      the asymptotic scaling behavior of the entropy.

PMID- 23129619
TI  - Extraordinary genome stability in the ciliate Paramecium tetraurelia.
AB  - Mutation plays a central role in all evolutionary processes and is also the basis
      of genetic disorders. Established base-substitution mutation rates in eukaryotes
      range between ~5 * 10(-10) and 5 * 10(-8) per site per generation, but here we
      report a genome-wide estimate for Paramecium tetraurelia that is more than an
      order of magnitude lower than any previous eukaryotic estimate. Nevertheless,
      when the mutation rate per cell division is extrapolated to the length of the
      sexual cycle for this protist, the measure obtained is comparable to that for
      multicellular species with similar genome sizes. Because Paramecium has a
      transcriptionally silent germ-line nucleus, these results are consistent with the
      hypothesis that natural selection operates on the cumulative germ-line
      replication fidelity per episode of somatic gene expression, with the germ-line
      mutation rate per cell division evolving downward to the lower barrier imposed by
      random genetic drift. We observe ciliate-specific modifications of widely
      conserved amino acid sites in DNA polymerases as one potential explanation for
      unusually high levels of replication fidelity.

PMID- 23129620
TI  - Turning self-destructing Salmonella into a universal DNA vaccine delivery
      platform.
AB  - We previously developed a biological containment system using recombinant
      Salmonella Typhimurium strains that are attenuated yet capable of synthesizing
      protective antigens. The regulated delayed attenuation and programmed self
      destructing features designed into these S. Typhimurium strains enable them to
      efficiently colonize host tissues and allow release of the bacterial cell
      contents after lysis. To turn such a recombinant attenuated Salmonella vaccine
      (RASV) strain into a universal DNA vaccine-delivery vehicle, our approach was to
      genetically modify RASV strains to display a hyperinvasive phenotype to maximize
      Salmonella host entry and host cell internalization, to enable Salmonella
      endosomal escape to release a DNA vaccine into the cytosol, and to decrease
      Salmonella-induced pyroptosis/apoptosis that allows the DNA vaccine time to
      traffic to the nucleus for efficient synthesis of encoded protective antigens. A
      DNA vaccine vector that encodes a domain that contributes to the arabinose
      regulated lysis phenotype but has a eukaryotic promoter was constructed. The
      vector was then improved by insertion of multiple DNA nuclear-targeting sequences
      for efficient nuclear trafficking and gene expression, and by increasing nuclease
      resistance to protect the plasmid from host degradation. A DNA vaccine encoding
      influenza WSN virus HA antigen delivered by the RASV strain with the best genetic
      attributes induced complete protection to mice against a lethal influenza virus
      challenge. Adoption of these technological improvements will revolutionize means
      for effective delivery of DNA vaccines to stimulate mucosal, systemic, and
      cellular protective immunities, and lead to a paradigm shift in cost-effective
      control and prevention of a diversity of diseases.

PMID- 23129621
TI  - Non-cell-autonomous regulation of crucifer self-incompatibility by Auxin Response
      Factor ARF3.
AB  - In many angiosperms, outcrossing is enforced by genetic self-incompatibility
      (SI), which allows cells of the pistil to recognize and specifically inhibit
      "self" pollen. SI is often associated with increased stigma-anther separation, a
      morphological trait that promotes cross-pollen deposition on the stigma. However,
      the gene networks responsible for coordinate evolution of these complex
      outbreeding devices are not known. In self-incompatible members of the
      Brassicaceae (crucifers), the inhibition of "self"-pollen is triggered within the
      stigma epidermal cell by allele-specific interaction between two highly
      polymorphic proteins, the stigma-expressed S-locus receptor kinase (SRK) and its
      pollen coat-localized ligand, the S-locus cysteine-rich (SCR) protein. Using
      Arabidopsis thaliana plants that express SI as a result of transformation with a
      functional SRK-SCR gene pair, we identify Auxin Response Factor 3 (ARF3) as a
      mediator of cross-talk between SI signaling and pistil development. We show that
      ARF3, a regulator of pistil development that is expressed in the vascular tissue
      of the style, acts non-cell-autonomously to enhance the SI response and
      simultaneously down-regulate auxin responses in stigma epidermal cells, likely by
      regulating a mobile signal derived from the stylar vasculature. The inverse
      correlation we observed in stigma epidermal cells between the strength of SI and
      the levels of auxin inferred from activity of the auxin-responsive reporter
      DR5::GUS suggests that the dampening of auxin responses in the stigma epidermis
      promotes inhibition of "self" pollen in crucifer SI.

PMID- 23129623
TI  - Fluctuating gravity of Earth's core.

PMID- 23129622
TI  - Rapid fragmentation of neuronal networks at the onset of propofol-induced
      unconsciousness.
AB  - The neurophysiological mechanisms by which anesthetic drugs cause loss of
      consciousness are poorly understood. Anesthetic actions at the molecular,
      cellular, and systems levels have been studied in detail at steady states of deep
      general anesthesia. However, little is known about how anesthetics alter neural
      activity during the transition into unconsciousness. We recorded simultaneous
      multiscale neural activity from human cortex, including ensembles of single
      neurons, local field potentials, and intracranial electrocorticograms, during
      induction of general anesthesia. We analyzed local and global neuronal network
      changes that occurred simultaneously with loss of consciousness. We show that
      propofol-induced unconsciousness occurs within seconds of the abrupt onset of a
      slow (<1 Hz) oscillation in the local field potential. This oscillation marks a
      state in which cortical neurons maintain local patterns of network activity, but
      this activity is fragmented across both time and space. Local (<4 mm) neuronal
      populations maintain the millisecond-scale connectivity patterns observed in the
      awake state, and spike rates fluctuate and can reach baseline levels. However,
      neuronal spiking occurs only within a limited slow oscillation-phase window and
      is silent otherwise, fragmenting the time course of neural activity.
      Unexpectedly, we found that these slow oscillations occur asynchronously across
      cortex, disrupting functional connectivity between cortical areas. We conclude
      that the onset of slow oscillations is a neural correlate of propofol-induced
      loss of consciousness, marking a shift to cortical dynamics in which local
      neuronal networks remain intact but become functionally isolated in time and
      space.

PMID- 23129624
TI  - Shear-induced phase transition of nanocrystalline hexagonal boron nitride to
      wurtzitic structure at room temperature and lower pressure.
AB  - Disordered structures of boron nitride (BN), graphite, boron carbide (BC), and
      boron carbon nitride (BCN) systems are considered important precursor materials
      for synthesis of superhard phases in these systems. However, phase transformation
      of such materials can be achieved only at extreme pressure-temperature
      conditions, which is irrelevant to industrial applications. Here, the phase
      transition from disordered nanocrystalline hexagonal (h)BN to superhard wurtzitic
      (w)BN was found at room temperature under a pressure of 6.7 GPa after applying
      large plastic shear in a rotational diamond anvil cell (RDAC) monitored by in
      situ synchrotron X-ray diffraction (XRD) measurements. However, under hydrostatic
      compression to 52.8 GPa, the same hBN sample did not transform to wBN but
      probably underwent a reversible transformation to a high-pressure disordered
      phase with closed-packed buckled layers. The current phase-transition pressure is
      the lowest among all reported direct-phase transitions from hBN to wBN at room
      temperature. Usually, large plastic straining leads to disordering and
      amorphization; here, in contrast, highly disordered hBN transformed to
      crystalline wBN. The mechanisms of strain-induced phase transformation and the
      reasons for such a low transformation pressure are discussed. Our results
      demonstrate a potential of low pressure-room temperature synthesis of superhard
      materials under plastic shear from disordered or amorphous precursors. They also
      open a pathway of phase transformation of nanocrystalline materials and materials
      with disordered and amorphous structures under extensive shear.

PMID- 23129625
TI  - Sensitivity of human lung adenocarcinoma cell lines to targeted inhibition of BET
      epigenetic signaling proteins.
AB  - Bromodomain and extra terminal domain (BET) proteins function as epigenetic
      signaling factors that associate with acetylated histones and facilitate
      transcription of target genes. Inhibitors targeting the activity of BET proteins
      have shown potent antiproliferative effects in hematological cancers through the
      suppression of c-MYC and downstream target genes. However, as the epigenetic
      landscape of a cell varies drastically depending on lineage, transcriptional
      coactivators such as BETs would be expected to have different targets in cancers
      derived from different cells of origin, and this may influence the activity and
      mechanism of action of BET inhibitors. To test this hypothesis, we treated a
      panel of lung adenocarcinoma (LAC) cell lines with the BET inhibitor JQ1 and
      found that a subset is acutely susceptible to BET inhibition. In contrast to
      blood tumors, we show that LAC cells are inhibited by JQ1 through a mechanism
      independent of c-MYC down-regulation. Through gene expression profiling, we
      discovered that the oncogenic transcription factor FOSL1 and its targets are
      suppressed by JQ1 in a dose-dependant manner. Knockdown of BRD4 also decreased
      FOSL1 levels, and inhibition of FOSL1 phenocopied the effects of JQ1 treatment,
      suggesting that loss of this transcription factor may be partly responsible for
      the cytotoxic effects of BET inhibition in LAC cells, although ectopic expression
      of FOSL1 alone did not rescue the phenotype. Together, these findings suggest
      that BET inhibitors may be useful in solid tumors and that cell-lineage-specific
      differences in transcriptional targets of BETs may influence the activity of
      inhibitors of these proteins in different cancer types.

PMID- 23129626
TI  - Autotrophy as a predominant mode of carbon fixation in anaerobic methane
      oxidizing microbial communities.
AB  - The methane-rich, hydrothermally heated sediments of the Guaymas Basin are
      inhabited by thermophilic microorganisms, including anaerobic methane-oxidizing
      archaea (mainly ANME-1) and sulfate-reducing bacteria (e.g., HotSeep-1 cluster).
      We studied the microbial carbon flow in ANME-1/ HotSeep-1 enrichments in stable
      isotope-probing experiments with and without methane. The relative incorporation
      of (13)C from either dissolved inorganic carbon or methane into lipids revealed
      that methane-oxidizing archaea assimilated primarily inorganic carbon. This
      assimilation is strongly accelerated in the presence of methane. Experiments with
      simultaneous amendments of both (13)C-labeled dissolved inorganic carbon and
      deuterated water provided further insights into production rates of individual
      lipids derived from members of the methane-oxidizing community as well as their
      carbon sources used for lipid biosynthesis. In the presence of methane, all
      prominent lipids carried a dual isotopic signal indicative of their origin from
      primarily autotrophic microbes. In the absence of methane, archaeal lipid
      production ceased and bacterial lipid production dropped by 90%; the lipids
      produced by the residual fraction of the metabolically active bacterial community
      predominantly carried a heterotrophic signal. Collectively our results strongly
      suggest that the studied ANME-1 archaea oxidize methane but assimilate inorganic
      carbon and should thus be classified as methane-oxidizing chemoorganoautotrophs.

PMID- 23129627
TI  - On flying insect size and Phanerozoic atmospheric oxygen.

PMID- 23129628
TI  - Estimating divergence times in large molecular phylogenies.
AB  - Molecular dating of species divergences has become an important means to add a
      temporal dimension to the Tree of Life. Increasingly larger datasets encompassing
      greater taxonomic diversity are becoming available to generate molecular
      timetrees by using sophisticated methods that model rate variation among
      lineages. However, the practical application of these methods is challenging
      because of the exorbitant calculation times required by current methods for
      contemporary data sizes, the difficulty in correctly modeling the rate
      heterogeneity in highly diverse taxonomic groups, and the lack of reliable clock
      calibrations and their uncertainty distributions for most groups of species.
      Here, we present a method that estimates relative times of divergences for all
      branching points (nodes) in very large phylogenetic trees without assuming a
      specific model for lineage rate variation or specifying any clock calibrations.
      The method (RelTime) performed better than existing methods when applied to very
      large computer simulated datasets where evolutionary rates were varied
      extensively among lineages by following autocorrelated and uncorrelated models.
      On average, RelTime completed calculations 1,000 times faster than the fastest
      Bayesian method, with even greater speed difference for larger number of
      sequences. This speed and accuracy will enable molecular dating analysis of very
      large datasets. Relative time estimates will be useful for determining the
      relative ordering and spacing of speciation events, identifying lineages with
      significantly slower or faster evolutionary rates, diagnosing the effect of
      selected calibrations on absolute divergence times, and estimating absolute times
      of divergence when highly reliable calibration points are available.

PMID- 23129629
TI  - Non-Bloom syndrome-associated partial and total loss-of-function variants of BLM
      helicase.
AB  - Bloom syndrome (BS) is an autosomal recessive disorder caused by mutations in the
      RecQ-like DNA helicase BLM, which functions in the maintenance of genome
      stability. Using a humanized model of Saccharomyces cerevisiae that expresses a
      chimera of the N terminus of yeast Sgs1 and the C terminus of human BLM from the
      chromosomal SGS1 locus, we have functionally evaluated 27 BLM alleles that are
      not currently known to be associated with BS. We identified nine alleles with
      impaired function when assessed for hypersensitivity to the DNA-damaging agent
      hydroxyurea (HU). Six of these alleles (P690L, R717T, W803R, Y811C, F857L, G972V)
      caused sensitivity to HU that was comparable to known BS-associated or helicase
      dead alleles, suggesting that they may cause BS and, in the heterozygous state,
      act as risk factors for cancerogenesis. We also identified three alleles (R791C,
      P868L, G1120R) that caused intermediate sensitivity to HU; although unlikely to
      cause BS, these partial loss-of-function alleles may increase risk for cancers or
      other BS-associated complications if a person is homozygous or compound
      heterozygous for these alleles or if they carry a known BS-associated allele.

PMID- 23129630
TI  - Formation of triple-helical structures by the 3'-end sequences of MALAT1 and
      MENbeta noncoding RNAs.
AB  - Stability of the long noncoding-polyadenylated nuclear (PAN) RNA from Kaposi's
      sarcoma-associated herpesvirus is conferred by an expression and nuclear
      retention element (ENE). The ENE protects PAN RNA from a rapid deadenylation
      dependent decay pathway via formation of a triple helix between the U-rich
      internal loop of the ENE and the 3'-poly(A) tail. Because viruses borrow
      molecular mechanisms from their hosts, we searched highly abundant human long
      noncoding RNAs and identified putative ENE-like structures in metastasis
      associated lung adenocarcinoma transcript 1 (MALAT1) and multiple endocrine
      neoplasia-beta (MENbeta) RNAs. Unlike the PAN ENE, the U-rich internal loops of
      both predicted cellular ENEs are interrupted by G and C nucleotides and reside
      upstream of genomically encoded A-rich tracts. We confirmed the ability of MALAT1
      and MENbeta sequences containing the predicted ENE and A-rich tract to increase
      the levels of an intronless beta-globin reporter RNA. UV thermal denaturation
      profiles at different pH values support formation of a triple-helical structure
      composed of multiple U*A-U base triples and a single C*G-C base triple.
      Additional analyses of the MALAT1 ENE revealed that robust stabilization activity
      requires an intact triple helix, strong stems at the duplex-triplex junctions, a
      G-C base pair flanking the triplex to mediate potential A-minor interactions, and
      the 3'-terminal A of the A-rich tract to form a blunt-ended triplex lacking
      unpaired nucleotides at the duplex-triplex junction. These examples of triple
      helical, ENE-like structures in cellular noncoding RNAs, are unique.

PMID- 23129631
TI  - Energy-dispersive X-ray emission spectroscopy using an X-ray free-electron laser
      in a shot-by-shot mode.
AB  - The ultrabright femtosecond X-ray pulses provided by X-ray free-electron lasers
      open capabilities for studying the structure and dynamics of a wide variety of
      systems beyond what is possible with synchrotron sources. Recently, this "probe
      before-destroy" approach has been demonstrated for atomic structure determination
      by serial X-ray diffraction of microcrystals. There has been the question whether
      a similar approach can be extended to probe the local electronic structure by X
      ray spectroscopy. To address this, we have carried out femtosecond X-ray emission
      spectroscopy (XES) at the Linac Coherent Light Source using redox-active Mn
      complexes. XES probes the charge and spin states as well as the ligand
      environment, critical for understanding the functional role of redox-active metal
      sites. Kbeta(1,3) XES spectra of Mn(II) and Mn(2)(III,IV) complexes at room
      temperature were collected using a wavelength dispersive spectrometer and
      femtosecond X-ray pulses with an individual dose of up to >100 MGy. The spectra
      were found in agreement with undamaged spectra collected at low dose using
      synchrotron radiation. Our results demonstrate that the intact electronic
      structure of redox active transition metal compounds in different oxidation
      states can be characterized with this shot-by-shot method. This opens the door
      for studying the chemical dynamics of metal catalytic sites by following
      reactions under functional conditions. The technique can be combined with X-ray
      diffraction to simultaneously obtain the geometric structure of the overall
      protein and the local chemistry of active metal sites and is expected to prove
      valuable for understanding the mechanism of important metalloproteins, such as
      photosystem II.

PMID- 23129632
TI  - Histone demethylase JMJD2C is a coactivator for hypoxia-inducible factor 1 that
      is required for breast cancer progression.
AB  - Hypoxia-inducible factor 1 (HIF-1) activates transcription of genes encoding
      proteins that play key roles in breast cancer biology. We hypothesized that
      interaction of HIF-1 with epigenetic regulators may increase HIF-1
      transcriptional activity, and thereby promote breast cancer progression. We
      report that the histone demethylase jumonji domain containing protein 2C (JMJD2C)
      selectively interacts with HIF-1alpha, but not HIF-2alpha, and that HIF-1alpha
      mediates recruitment of JMJD2C to the hypoxia response elements of HIF-1 target
      genes. JMJD2C decreases trimethylation of histone H3 at lysine 9, and enhances
      HIF-1 binding to hypoxia response elements, thereby activating transcription of
      BNIP3, LDHA, PDK1, and SLC2A1, which encode proteins that are required for
      metabolic reprogramming, as well as LOXL2 and L1CAM, which encode proteins that
      are required for lung metastasis. JMJD2C expression is significantly associated
      with expression of GLUT1, LDHA, PDK1, LOX, LOXL2, and L1CAM mRNA in human breast
      cancer biopsies. JMJD2C knockdown inhibits breast tumor growth and spontaneous
      metastasis to the lungs of mice following mammary fat pad injection. Taken
      together, these findings establish an important epigenetic mechanism that
      stimulates HIF-1-mediated transactivation of genes encoding proteins involved in
      metabolic reprogramming and lung metastasis in breast cancer.

PMID- 23129633
TI  - Encounter with antigen-specific primed CD4 T cells promotes MHC class II
      degradation in dendritic cells.
AB  - Major histocompatibility complex class II molecules (MHC-II) on antigen
      presenting cells (APCs) engage the TCR on antigen-specific CD4 T cells, thereby
      providing the specificity required for T cell priming and the induction of an
      effective immune response. In this study, we have asked whether antigen-loaded
      dendritic cells (DCs) that have been in contact with antigen-specific CD4 T cells
      retain the ability to stimulate additional naive T cells. We show that encounter
      with antigen-specific primed CD4 T cells induces the degradation of surface MHC
      II in antigen-loaded DCs and inhibits the ability of these DCs to stimulate
      additional naive CD4 T cells. Cross-linking with MHC-II mAb as a surrogate for T
      cell engagement also inhibits APC function and induces MHC-II degradation by
      promoting the clustering of MHC-II present in lipid raft membrane microdomains, a
      process that leads to MHC-II endocytosis and degradation in lysosomes. Encounter
      of DCs with antigen-specific primed T cells or engagement of MHC-II with
      antibodies promotes the degradation of both immunologically relevant and
      irrelevant MHC-II molecules. These data demonstrate that engagement of MHC-II on
      DCs after encounter with antigen-specific primed CD4 T cells promotes the down
      regulation of cell surface MHC-II in DCs, thereby attenuating additional
      activation of naive CD4 T cells by these APCs.

PMID- 23129634
TI  - Redundant phenazine operons in Pseudomonas aeruginosa exhibit environment
      dependent expression and differential roles in pathogenicity.
AB  - Evolutionary biologists have postulated that several fitness advantages may be
      conferred by the maintenance of duplicate genes, including environmental
      adaptation resulting from differential regulation. We examined the expression and
      physiological contributions of two redundant operons in the adaptable bacterium
      Pseudomonas aeruginosa PA14. These operons, phzA1-G1 (phz1) and phzA2-G2 (phz2),
      encode nearly identical sets of proteins that catalyze the synthesis of phenazine
      1-carboxylic acid, the precursor for several phenazine derivatives. Phenazines
      perform diverse roles in P. aeruginosa physiology and act as virulence factors
      during opportunistic infections of plant and animal hosts. Although reports have
      indicated that phz1 is regulated by the Pseudomonas quinolone signal, factors
      controlling phz2 expression have not been identified, and the relative
      contributions of these redundant operons to phenazine biosynthesis have not been
      evaluated. We found that in liquid cultures, phz1 was expressed at higher levels
      than phz2, although phz2 showed a greater contribution to phenazine production.
      In colony biofilms, phz2 was expressed at high levels, whereas phz1 expression
      was not detectable, and phz2 was responsible for virtually all phenazine
      production. Analysis of mutants defective in quinolone signal synthesis revealed
      a critical role for 4-hydroxy-2-heptylquinoline in phz2 induction. Finally,
      deletion of phz2, but not of phz1, decreased lung colonization in a murine model
      of infection. These results suggest that differential regulation of the redundant
      phz operons allows P. aeruginosa to adapt to diverse environments.

PMID- 23129635
TI  - Background-dependent effects of polyglutamine variation in the Arabidopsis
      thaliana gene ELF3.
AB  - Tandem repeats (TRs) have extremely high mutation rates and are often considered
      to be neutrally evolving DNA. However, in coding regions, TR copy number
      mutations can significantly affect phenotype and may facilitate rapid adaptation
      to new environments. In several human genes, TR copy number mutations that expand
      polyglutamine (polyQ) tracts beyond a certain threshold cause incurable
      neurodegenerative diseases. PolyQ-containing proteins exist at a considerable
      frequency in eukaryotes, yet the phenotypic consequences of natural variation in
      polyQ tracts that are not associated with disease remain largely unknown. Here,
      we use Arabidopsis thaliana to dissect the phenotypic consequences of natural
      variation in the polyQ tract encoded by EARLY FLOWERING 3 (ELF3), a key
      developmental gene. Changing ELF3 polyQ tract length affected complex ELF3
      dependent phenotypes in a striking and nonlinear manner. Some natural ELF3 polyQ
      variants phenocopied elf3 loss-of-function mutants in a common reference
      background, although they are functional in their native genetic backgrounds. To
      test the existence of background-specific modifiers, we compared the phenotypic
      effects of ELF3 polyQ variants between two divergent backgrounds, Col and Ws, and
      found dramatic differences. In fact, the Col-ELF3 allele, encoding the shortest
      known ELF3 polyQ tract, was haploinsufficient in Ws * Col F(1) hybrids. Our data
      support a model in which variable polyQ tracts drive adaptation to internal
      genetic environments.

PMID- 23129636
TI  - Mechanistic insights into editing-site specificity of ADARs.
AB  - Adenosine deaminases that act on RNA (ADARs) deaminate adenosines in dsRNA to
      produce inosines. ADARs are essential in mammals and are particularly important
      in the nervous system. Altered levels of adenosine-to-inosine (A-to-I) editing
      are observed in several diseases. The extent to which an adenosine is edited
      depends on sequence context. Human ADAR2 (hADAR2) has 5' and 3' neighbor
      preferences, but which amino acids mediate these preferences, and by what
      mechanism, is unknown. We performed a screen in yeast to identify mutations in
      the hADAR2 catalytic domain that allow editing of an adenosine within a
      disfavored triplet. Binding affinity, catalytic rate, base flipping, and
      preferences were monitored to understand the effects of the mutations on ADAR
      reactivity. Our data provide information on the amino acids that affect
      preferences and point to a conserved loop as being of key importance.
      Unexpectedly, our data suggest that hADAR2's preferences derive from differential
      base flipping rather than from direct recognition of neighboring bases. Our
      studies set the stage for understanding the basis of altered editing levels in
      disease and for developing therapeutic reagents.

PMID- 23129637
TI  - Early responses to adenoviral-mediated transfer of the aquaporin-1 cDNA for
      radiation-induced salivary hypofunction.
AB  - No conventional therapy exists for salivary hypofunction in surviving head and
      neck cancer patients with Radiation Therapy Oncology Group late grade 2-3
      toxicity. We conducted a phase I clinical trial to test the safety and biologic
      efficacy of serotype 5, adenoviral-mediated aquaporin-1 cDNA transfer to a single
      previously irradiated parotid gland in 11 subjects using an open label, single
      dose, dose-escalation design (AdhAQP1 vector; four dose tiers from 4.8 * 10(7) to
      5.8 * 10(9) vector particles per gland). Treated subjects were followed at
      scheduled intervals. Multiple safety parameters were measured and biologic
      efficacy was evaluated with measurements of parotid salivary flow rate. Symptoms
      were assessed with a visual analog scale. All subjects tolerated vector delivery
      and study procedures well over the 42-d study period reported. No deaths, serious
      adverse events, or dose-limiting toxicities occurred. Generally, few adverse
      events occurred, and all were considered mild or moderate. No consistent changes
      were found in any clinical chemistry and hematology parameters measured.
      Objective responses were seen in six subjects, all at doses <5.8 * 10(9) vector
      particles per gland. Five of these six subjects also experienced subjective
      improvement in xerostomia. AdhAQP1 vector delivery to a single parotid gland was
      safe and transfer of the hAQP1 cDNA increased parotid flow and relieved symptoms
      in a subset of subjects.

PMID- 23129638
TI  - Image sequence reactivation in awake V4 networks.
AB  - In the absence of sensory input, neuronal networks are far from being silent.
      Whether spontaneous changes in ongoing activity reflect previous sensory
      experience or stochastic fluctuations in brain activity is not well understood.
      Here we describe reactivation of stimulus-evoked activity in awake visual
      cortical networks. We found that continuous exposure to randomly flashed image
      sequences induces reactivation in macaque V4 cortical networks in the absence of
      visual stimulation. This reactivation of previously evoked activity is stimulus
      specific, occurs only in the same temporal order as the original response, and
      strengthens with increased stimulus exposures. Importantly, cells exhibiting
      significant reactivation carry more information about the stimulus than cells
      that do not reactivate. These results demonstrate a surprising degree of
      experience-dependent plasticity in visual cortical networks as a result of
      repeated exposure to unattended information. We suggest that awake reactivation
      in visual cortex may underlie perceptual learning by passive stimulus exposure.

PMID- 23129639
TI  - A mouse model for human deafness DFNB22 reveals that hearing impairment is due to
      a loss of inner hair cell stimulation.
AB  - The gene causative for the human nonsyndromic recessive form of deafness DFNB22
      encodes otoancorin, a 120-kDa inner ear-specific protein that is expressed on the
      surface of the spiral limbus in the cochlea. Gene targeting in ES cells was used
      to create an EGFP knock-in, otoancorin KO (Otoa(EGFP/EGFP)) mouse. In the
      Otoa(EGFP/EGFP) mouse, the tectorial membrane (TM), a ribbon-like strip of ECM
      that is normally anchored by one edge to the spiral limbus and lies over the
      organ of Corti, retains its general form, and remains in close proximity to the
      organ of Corti, but is detached from the limbal surface. Measurements of cochlear
      microphonic potentials, distortion product otoacoustic emissions, and basilar
      membrane motion indicate that the TM remains functionally attached to the
      electromotile, sensorimotor outer hair cells of the organ of Corti, and that the
      amplification and frequency tuning of the basilar membrane responses to sounds
      are almost normal. The compound action potential masker tuning curves, a measure
      of the tuning of the sensory inner hair cells, are also sharply tuned, but the
      thresholds of the compound action potentials, a measure of inner hair cell
      sensitivity, are significantly elevated. These results indicate that the hearing
      loss in patients with Otoa mutations is caused by a defect in inner hair cell
      stimulation, and reveal the limbal attachment of the TM plays a critical role in
      this process.

PMID- 23129640
TI  - Simultaneous, accurate measurement of the 3D position and orientation of single
      molecules.
AB  - Recently, single molecule-based superresolution fluorescence microscopy has
      surpassed the diffraction limit to improve resolution to the order of 20 nm or
      better. These methods typically use image fitting that assumes an isotropic
      emission pattern from the single emitters as well as control of the emitter
      concentration. However, anisotropic single-molecule emission patterns arise from
      the transition dipole when it is rotationally immobile, depending highly on the
      molecule's 3D orientation and z position. Failure to account for this fact can
      lead to significant lateral (x, y) mislocalizations (up to ~50-200 nm). This
      systematic error can cause distortions in the reconstructed images, which can
      translate into degraded resolution. Using parameters uniquely inherent in the
      double-lobed nature of the Double-Helix Point Spread Function, we account for
      such mislocalizations and simultaneously measure 3D molecular orientation and 3D
      position. Mislocalizations during an axial scan of a single molecule manifest
      themselves as an apparent lateral shift in its position, which causes the
      standard deviation (SD) of its lateral position to appear larger than the SD
      expected from photon shot noise. By correcting each localization based on an
      estimated orientation, we are able to improve SDs in lateral localization from
      ~2* worse than photon-limited precision (48 vs. 25 nm) to within 5 nm of photon
      limited precision. Furthermore, by averaging many estimations of orientation over
      different depths, we are able to improve from a lateral SD of 116 (~4* worse than
      the photon-limited precision; 28 nm) to 34 nm (within 6 nm of the photon limit).

PMID- 23129641
TI  - Kinetic mechanism for viral dsRNA length discrimination by MDA5 filaments.
AB  - The viral sensor MDA5 distinguishes between cellular and viral dsRNAs by length
      dependent recognition in the range of ~0.5-7 kb. The ability to discriminate
      dsRNA length at this scale sets MDA5 apart from other dsRNA receptors of the
      immune system. We have shown previously that MDA5 forms filaments along dsRNA
      that disassemble upon ATP hydrolysis. Here, we demonstrate that filament
      formation alone is insufficient to explain its length specificity, because the
      intrinsic affinity of MDA5 for dsRNA depends only moderately on dsRNA length.
      Instead, MDA5 uses a combination of end disassembly and slow nucleation kinetics
      to "discard" short dsRNA rapidly and to suppress rebinding. In contrast,
      filaments on long dsRNA cycle between partial end disassembly and elongation,
      bypassing nucleation steps. MDA5 further uses this repetitive cycle of assembly
      and disassembly processes to repair filament discontinuities, which often are
      present because of multiple, internal nucleation events, and to generate longer,
      continuous filaments that more accurately reflect the length of the underlying
      dsRNA scaffold. Because the length of the continuous filament determines the
      stability of the MDA5-dsRNA interaction, the mechanism proposed here provides an
      explanation for how MDA5 uses filament assembly and disassembly dynamics to
      discriminate between self vs. nonself dsRNA.

PMID- 23129643
TI  - Functional and structural analysis of the human SLO3 pH- and voltage-gated K+
      channel.
AB  - The activation of eukaryotic SLO K(+) channels by intracellular cues, mediated by
      a cytoplasmic structure called the gating ring, is central to their physiological
      roles. SLO3 channels are exclusively expressed in mammalian sperm, where
      variations of intracellular pH are critical to cellular function. Previous
      studies primarily focused on the mouse SLO3 orthologue and revealed that, in
      murine sperm, SLO3 mediates a voltage- and alkalization-activated K(+) current
      essential to male fertility. Here we investigate the activation of the human SLO3
      channel by intracellular pH at the functional and structural level. By using
      electrophysiology in a heterologous system, we show that human SLO3 opens upon
      intracellular pH increase and that its expression and functional properties are
      modulated by LRRC52, a testis-specific accessory subunit. We next present the
      crystal structure of the human SLO3 gating ring. Comparison with the known
      structures of the corresponding domain from SLO1, a Ca(2+)-activated homologue,
      suggests that the SLO3 gating ring structure may represent an open state.
      Together, these results present insights into the function of a protein expected
      to be critical for human reproduction and provide a framework to study the
      mechanism of pH gating in SLO3 channels.

PMID- 23129644
TI  - Genetic evidence that brain-derived neurotrophic factor mediates competitive
      interactions between individual cortical neurons.
AB  - Brain-derived neurotrophic factor (BDNF) is a secreted protein important for
      development and function of neocortical circuitry. Although it is well
      established that BDNF contributes to the sculpting of dendrite structure and
      modulation of synapse strength, the range and directionality of BDNF signaling
      underlying these functions are incompletely understood. To gain insights into the
      role of BDNF at the level of individual neurons, we tested the cell-autonomous
      requirements for Bdnf in visual cortical layer 2/3 neurons. We found that the
      number of functional Bdnf alleles a neuron carries relative to the prevailing
      genotype determines its density of dendritic spines, the structures at which most
      excitatory synapses are made. This requirement for Bdnf exists both during
      postnatal development and in adulthood, suggesting that the amount of BDNF a
      neuron is capable of producing determines its success in ongoing competition in
      the environment of the neocortex. Our results suggest that BDNF may perform a
      long-sought function for a secreted growth factor in mediating the competitive
      events that shape individual neurons and their circuits.

PMID- 23129645
TI  - Warming-induced reductions in body size are greater in aquatic than terrestrial
      species.
AB  - Most ectothermic organisms mature at smaller body sizes when reared in warmer
      conditions. This phenotypically plastic response, known as the "temperature-size
      rule" (TSR), is one of the most taxonomically widespread patterns in biology.
      However, the TSR remains a longstanding life-history puzzle for which no dominant
      driver has been found. We propose that oxygen supply plays a central role in
      explaining the magnitude of ectothermic temperature-size responses. Given the
      much lower oxygen availability and greater effort required to increase uptake in
      water vs. air, we predict that the TSR in aquatic organisms, especially larger
      species with lower surface area-body mass ratios, will be stronger than in
      terrestrial organisms. We performed a meta-analysis of 1,890 body mass responses
      to temperature in controlled experiments on 169 terrestrial, freshwater, and
      marine species. This reveals that the strength of the temperature-size response
      is greater in aquatic than terrestrial species. In animal species of ~100 mg dry
      mass, the temperature-size response of aquatic organisms is 10 times greater than
      in terrestrial organisms (-5.0%  degrees C(-1) vs. -0.5%  degrees C(-1)).
      Moreover, although the size response of small (<0.1 mg dry mass) aquatic and
      terrestrial species is similar, increases in species size cause the response to
      become increasingly negative in aquatic species, as predicted, but on average
      less negative in terrestrial species. These results support oxygen as a major
      driver of temperature-size responses in aquatic organisms. Further, the
      environment-dependent differences parallel latitudinal body size clines, and will
      influence predicted impacts of climate warming on food production, community
      structure, and food-web dynamics.

PMID- 23129646
TI  - Developmental stage-specific metabolic and transcriptional activity of Chlamydia
      trachomatis in an axenic medium.
AB  - Chlamydia trachomatis is among the most clinically significant human pathogens,
      yet their obligate intracellular nature places severe restrictions upon research.
      Chlamydiae undergo a biphasic developmental cycle characterized by an infectious
      cell type known as an elementary body (EB) and an intracellular replicative form
      called a reticulate body (RB). EBs have historically been described as
      metabolically dormant. A cell-free (axenic) culture system was developed, which
      showed high levels of metabolic and biosynthetic activity from both EBs and RBs,
      although the requirements differed for each. EBs preferentially used glucose-6
      phosphate as an energy source, whereas RBs required ATP. Both developmental forms
      showed increased activity when incubated under microaerobic conditions.
      Incorporation of isotopically labeled amino acids into proteins from both
      developmental forms indicated unique expression profiles, which were confirmed by
      genome-wide transcriptional analysis. The described axenic culture system will
      greatly enhance biochemical and physiological analyses of chlamydiae.

PMID- 23129647
TI  - Bioinformatic identification of genes suppressing genome instability.
AB  - Unbiased forward genetic screens for mutations causing increased gross
      chromosomal rearrangement (GCR) rates in Saccharomyces cerevisiae are hampered by
      the difficulty in reliably using qualitative GCR assays to detect mutants with
      small but significantly increased GCR rates. We therefore developed a
      bioinformatic procedure using genome-wide functional genomics screens to identify
      and prioritize candidate GCR-suppressing genes on the basis of the shared drug
      sensitivity suppression and similar genetic interactions as known GCR
      suppressors. The number of known suppressors was increased from 75 to 110 by
      testing 87 predicted genes, which identified unanticipated pathways in this
      process. This analysis explicitly dealt with the lack of concordance among high
      throughput datasets to increase the reliability of phenotypic predictions.
      Additionally, shared phenotypes in one assay were imperfect predictors for shared
      phenotypes in other assays, indicating that although genome-wide datasets can be
      useful in aggregate, caution and validation methods are required when deciphering
      biological functions via surrogate measures, including growth-based genetic
      interactions.

PMID- 23129648
TI  - Predictive energy landscapes for protein-protein association.
AB  - We investigate protein-protein association using the associative-memory, water
      mediated, structure, and energy model (AWSEM), a coarse-grained protein folding
      model that has been optimized using energy-landscape theory. The potential was
      originally parameterized by enforcing a funneled nature for a database of dimeric
      interfaces but was later further optimized to create funneled folding landscapes
      for individual monomeric proteins. The ability of the model to predict interfaces
      was not tested previously. The present results show that simulated annealing of
      the model indeed is able to predict successfully the native interfaces of eight
      homodimers and four heterodimers, thus amounting to a flexible docking algorithm.
      We go on to address the relative importance of monomer geometry, flexibility, and
      nonnative intermonomeric contacts in the association process for the homodimers.
      Monomer surface geometry is found to be important in determining the binding
      interface, but it is insufficient. Using a uniform binding potential rather than
      the water-mediated potential results in sampling of misbound structures that are
      geometrically preferred but are nonetheless energetically disfavored by AWSEM, as
      well as in nature. Depending on the stability of the unbound monomers, nonnative
      contacts play different roles in the association process. For unstable monomers,
      thermodynamic states stabilized by nonnative interactions correspond to
      productive, on-pathway intermediates and can, therefore, catalyze binding through
      a fly-casting mechanism. For stable monomers, in contrast, states stabilized by
      nonnative interactions generally correspond to traps that impede binding.

PMID- 23129649
TI  - Deep-sea record of impact apparently unrelated to mass extinction in the Late
      Triassic.
AB  - The 34-million-year (My) interval of the Late Triassic is marked by the formation
      of several large impact structures on Earth. Late Triassic impact events have
      been considered a factor in biotic extinction events in the Late Triassic (e.g.,
      end-Triassic extinction event), but this scenario remains controversial because
      of a lack of stratigraphic records of ejecta deposits. Here, we report evidence
      for an impact event (platinum group elements anomaly with nickel-rich magnetite
      and microspherules) from the middle Norian (Upper Triassic) deep-sea sediment in
      Japan. This includes anomalously high abundances of iridium, up to 41.5 parts per
      billion (ppb), in the ejecta deposit, which suggests that the iridium-enriched
      ejecta layers of the Late Triassic may be found on a global scale. The ejecta
      deposit is constrained by microfossils that suggest correlation with the 215.5
      Mya, 100-km-wide Manicouagan impact crater in Canada. Our analysis of
      radiolarians shows no evidence of a mass extinction event across the impact event
      horizon, and no contemporaneous faunal turnover is seen in other marine
      planktons. However, such an event has been reported among marine faunas and
      terrestrial tetrapods and floras in North America. We, therefore, suggest that
      the Manicouagan impact triggered the extinction of terrestrial and marine
      organisms near the impact site but not within the pelagic marine realm.

PMID- 23129650
TI  - Identification and treatment of heme depletion attributed to overexpression of a
      lineage of evolved P450 monooxygenases.
AB  - Recent advances in metabolic engineering have demonstrated that microbial
      biosynthesis can provide a viable alternative to chemical synthesis for the
      production of bulk and fine chemicals. Introduction of a new biosynthetic pathway
      typically requires the expression of multiple heterologous enzymes in the
      production host, which can impose stress on the host cell and, thereby, limit
      performance of the pathway. Unfortunately, analysis and treatment of the host
      stress response can be difficult, because there are many sources of stress that
      may interact in complex ways. We use a systems biological approach to analyze the
      stress imposed by expressing different enzyme variants from a lineage of soluble
      P450 monooxygenases, previously evolved for heterologous activity in
      Saccharomyces cerevisiae. Our analysis identifies patterns of stress imposed on
      the host by heterologous enzyme overexpression that are consistent across the
      evolutionary lineage, ultimately implicating heme depletion as the major stress.
      We show that the monooxygenase evolution, starting from conditions of either high
      or low stress, caused the cellular stress to converge to a common level.
      Overexpression of rate-limiting enzymes in the endogenous heme biosynthetic
      pathway alleviates the stress imposed by expression of the P450 monooxygenases
      and increases the enzymatic activity of the final evolved P450 by an additional
      2.3-fold. Heme overexpression also increases the total activity of an endogenous
      cytosolic heme-containing catalase but not a heterologous P450 that is membrane
      associated. This work demonstrates the utility of combining systems and synthetic
      biology to analyze and optimize heterologous enzyme expression.

PMID- 23129651
TI  - Mouse mtDNA mutant model of Leber hereditary optic neuropathy.
AB  - An animal model of Leber hereditary optic neuropathy (LHON) was produced by
      introducing the human optic atrophy mtDNA ND6 P25L mutation into the mouse. Mice
      with this mutation exhibited reduction in retinal function by elecroretinogram
      (ERG), age-related decline in central smaller caliber optic nerve fibers with
      sparing of larger peripheral fibers, neuronal accumulation of abnormal
      mitochondria, axonal swelling, and demyelination. Mitochondrial analysis revealed
      partial complex I and respiration defects and increased reactive oxygen species
      (ROS) production, whereas synaptosome analysis revealed decreased complex I
      activity and increased ROS but no diminution of ATP production. Thus, LHON
      pathophysiology may result from oxidative stress.

PMID- 23129652
TI  - Most rhesus macaques infected with the CCR5-tropic SHIV(AD8) generate cross
      reactive antibodies that neutralize multiple HIV-1 strains.
AB  - The induction of broadly reacting neutralizing antibodies has been a major goal
      of HIV vaccine research. Characterization of a pathogenic CCR5 (R5)-tropic
      SIV/HIV chimeric virus (SHIV) molecular clone (SHIV(AD8-EO)) revealed that eight
      of eight infected animals developed cross-reactive neutralizing antibodies (NAbs)
      directed against an envelope glycoprotein derived from the heterologous HIV
      1(DH12) strain. A panel of plasmas, collected from monkeys inoculated with either
      molecularly cloned or uncloned SHIV(AD8) stocks, exhibited cross-neutralization
      against multiple tier 1 and tier 2 HIV-1 clade B isolates. One SHIV(AD8)-infected
      animal also developed NAbs against clades A and C HIV-1 strains. In this
      particular infected macaque, the cross-reacting anti-HIV-1 NAbs produced between
      weeks 7 and 13 were directed against a neutralization-sensitive virus strain,
      whereas neutralizing activities emerging at weeks 41-51 targeted more
      neutralization-resistant HIV-1 isolates. These results indicate that the
      SHIV(AD8) macaque model represents a potentially valuable experimental system for
      investigating B-cell maturation and the induction of cross-reactive NAbs directed
      against multiple HIV-1 strains.

PMID- 23129653
TI  - Dilatational band formation in bone.
AB  - Toughening in hierarchically structured materials like bone arises from the
      arrangement of constituent material elements and their interactions. Unlike
      microcracking, which entails micrometer-level separation, there is no known
      evidence of fracture at the level of bone's nanostructure. Here, we show that the
      initiation of fracture occurs in bone at the nanometer scale by dilatational
      bands. Through fatigue and indentation tests and laser confocal, scanning
      electron, and atomic force microscopies on human and bovine bone specimens, we
      established that dilatational bands of the order of 100 nm form as ellipsoidal
      voids in between fused mineral aggregates and two adjacent proteins, osteocalcin
      (OC) and osteopontin (OPN). Laser microdissection and ELISA of bone microdamage
      support our claim that OC and OPN colocalize with dilatational bands. Fracture
      tests on bones from OC and/or OPN knockout mice (OC(-/-), OPN(-/-), OC-OPN(-/-;-/
      )) confirm that these two proteins regulate dilatational band formation and bone
      matrix toughness. On the basis of these observations, we propose molecular
      deformation and fracture mechanics models, illustrating the role of OC and OPN in
      dilatational band formation, and predict that the nanometer scale of tissue
      organization, associated with dilatational bands, affects fracture at higher
      scales and determines fracture toughness of bone.

PMID- 23129654
TI  - Folding of the four-helix bundle FF domain from a compact on-pathway intermediate
      state is governed predominantly by water motion.
AB  - Friction plays a critical role in protein folding. Frictional forces originating
      from random solvent and protein fluctuations both retard motion along the folding
      pathway and activate protein molecules to cross free energy barriers. Studies of
      friction thus may provide insights into the driving forces underlying protein
      conformational dynamics. However, the molecular origin of friction in protein
      folding remains poorly understood because, with the exception of the native
      conformer, there generally is little detailed structural information on the other
      states participating in the folding process. Here, we study the folding of the
      four-helix bundle FF domain that proceeds via a transiently formed, sparsely
      populated compact on-pathway folding intermediate whose structure was elucidated
      previously. Because the intermediate is stabilized by both native and nonnative
      interactions, friction in the folding transition between intermediate and folded
      states is expected to arise from intrachain reorganization in the protein.
      However, the viscosity dependencies of rates of folding from or unfolding to the
      intermediate, as established by relaxation dispersion NMR spectroscopy, clearly
      indicate that contributions from internal friction are small relative to those
      from solvent, so solvent frictional forces drive the folding process. Our results
      emphasize the importance of solvent dynamics in mediating the interconversion
      between protein configurations, even those that are highly compact, and in
      equilibrium folding/unfolding fluctuations in general.

PMID- 23129655
TI  - Biogenic membranes of the chloroplast in Chlamydomonas reinhardtii.
AB  - The polypeptide subunits of the photosynthetic electron transport complexes in
      plants and algae are encoded by two genomes. Nuclear genome-encoded subunits are
      synthesized in the cytoplasm by 80S ribosomes, imported across the chloroplast
      envelope, and assembled with the subunits that are encoded by the plastid genome.
      Plastid genome-encoded subunits are synthesized by 70S chloroplast ribosomes
      directly into membranes that are widely believed to belong to the photosynthetic
      thylakoid vesicles. However, in situ evidence suggested that subunits of
      photosystem II are synthesized in specific regions within the chloroplast and
      cytoplasm of Chlamydomonas. Our results provide biochemical and in situ evidence
      of biogenic membranes that are localized to these translation zones. A
      "chloroplast translation membrane" is bound by the translation machinery and
      appears to be privileged for the synthesis of polypeptides encoded by the plastid
      genome. Membrane domains of the chloroplast envelope are located adjacent to the
      cytoplasmic translation zone and enriched in the translocons of the outer and
      inner chloroplast envelope membranes protein import complexes, suggesting a
      coordination of protein synthesis and import. Our findings contribute to a
      current realization that biogenic processes are compartmentalized within
      organelles and bacteria.

PMID- 23129657
TI  - Meltwater routing and the Younger Dryas.
AB  - The Younger Dryas--the last major cold episode on Earth--is generally considered
      to have been triggered by a meltwater flood into the North Atlantic. The
      prevailing hypothesis, proposed by Broecker et al. [1989 Nature 341:318-321] more
      than two decades ago, suggests that an abrupt rerouting of Lake Agassiz overflow
      through the Great Lakes and St. Lawrence Valley inhibited deep water formation in
      the subpolar North Atlantic and weakened the strength of the Atlantic Meridional
      Overturning Circulation (AMOC). More recently, Tarasov and Peltier [2005 Nature
      435:662-665] showed that meltwater could have discharged into the Arctic Ocean
      via the Mackenzie Valley ~4,000 km northwest of the St. Lawrence outlet. Here we
      use a sophisticated, high-resolution, ocean sea-ice model to study the delivery
      of meltwater from the two drainage outlets to the deep water formation regions in
      the North Atlantic. Unlike the hypothesis of Broecker et al., freshwater from the
      St. Lawrence Valley advects into the subtropical gyre ~3,000 km south of the
      North Atlantic deep water formation regions and weakens the AMOC by <15%. In
      contrast, narrow coastal boundary currents efficiently deliver meltwater from the
      Mackenzie Valley to the deep water formation regions of the subpolar North
      Atlantic and weaken the AMOC by >30%. We conclude that meltwater discharge from
      the Arctic, rather than the St. Lawrence Valley, was more likely to have
      triggered the Younger Dryas cooling.

PMID- 23129656
TI  - Splicing program of human MENA produces a previously undescribed isoform
      associated with invasive, mesenchymal-like breast tumors.
AB  - Human mena (hMENA), a member of the actin cytoskeleton regulators Ena/VASP, is
      overexpressed in high-risk preneoplastic lesions and in primary breast tumors and
      has been identified as playing a role in invasiveness and poor prognosis in
      breast cancers that express HER2. Here we identify a unique isoform,
      hMENADeltav6, derived from the hMENA alternative splicing program. In an isogenic
      model of human breast cancer progression, we show that hMENA(11a) is expressed in
      premalignant cells, whereas hMENADeltav6 expression is restricted to invasive
      cancer cells. "Reversion" of the malignant phenotype leads to concurrent down
      regulation of all hMENA isoforms. In breast cancer cell lines, isoform-specific
      hMENA overexpression or knockdown revealed that in the absence of hMENA(11a),
      overexpression of hMENADeltav6 increased cell invasion, whereas overexpression of
      hMENA(11a) reduced the migratory and invasive ability of these cells. hMENA(11a)
      splicing was shown to be dependent on the epithelial regulator of splicing 1
      (ESRP1), and forced expression of ESRP1 in invasive mesenchymal breast cancer
      cells caused a phenotypic switch reminiscent of a mesenchymal-to-epithelial
      transition (MET) characterized by changes in the cytoskeletal architecture,
      reexpression of hMENA(11a), and a reduction in cell invasion. hMENA-positive
      primary breast tumors, which are hMENA(11a)-negative, are more frequently E
      cadherin low in comparison with tumors expressing hMENA(11a). These data suggest
      that polarized and growth-arrested cellular architecture correlates with absence
      of alternative hMENA isoform expression, and that the hMENA splicing program is
      relevant to malignant progression in invasive disease.

PMID- 23129658
TI  - Dimerization of postsynaptic neuroligin drives synaptic assembly via
      transsynaptic clustering of neurexin.
AB  - The transsynaptic complex of neuroligin (NLGN) and neurexin forms a physical
      connection between pre- and postsynaptic neurons that occurs early in the course
      of new synapse assembly. Both neuroligin and neurexin have, indeed, been proposed
      to exhibit active, instructive roles in the formation of synapses. However, the
      process by which these instructive roles play out during synaptogenesis is not
      well understood. Here, we examine one aspect of postsynaptic neuroligin with
      regard to its synaptogenic properties: its basal state as a constitutive dimer.
      We show that dimerization is required for the synaptogenic properties of
      neuroligin and likely serves to induce presynaptic differentiation via a
      transsynaptic clustering of neurexin. Further, we introduce chemically inducible,
      exogenous dimerization domains to the neuroligin molecule, effectively bestowing
      chemical control of neuroligin dimerization. This allows us to identify the acute
      requirements of neuroligin dimerization by chemically manipulating the monomeric
      to-dimeric conversion of neuroligin. Based on the results of the inducible
      dimerization experiments, we propose a model in which dimerized neuroligin
      induces the mechanical clustering of presynaptic molecules as part of a requisite
      step in the coordinated assembly of a chemical synapse.

PMID- 23129659
TI  - Complex effects of nucleotide variants in a mammalian cis-regulatory element.
AB  - Cis-regulatory elements (CREs) control gene expression by recruiting
      transcription factors (TFs) and other DNA binding proteins. We aim to understand
      how individual nucleotides contribute to the function of CREs. Here we introduce
      CRE analysis by sequencing (CRE-seq), a high-throughput method for producing and
      testing large numbers of reporter genes in mammalian cells. We used CRE-seq to
      assay >1,000 single and double nucleotide mutations in a 52-bp CRE in the
      Rhodopsin promoter that drives strong and specific expression in mammalian
      photoreceptors. We find that this particular CRE is remarkably complex. The
      majority (86%) of single nucleotide substitutions in this sequence exert
      significant effects on regulatory activity. Although changes in the affinity of
      known TF binding sites explain some of these expression changes, we present
      evidence for complex phenomena, including binding site turnover and TF
      competition. Analysis of double mutants revealed complex, nucleotide-specific
      interactions between residues in different TF binding sites. We conclude that
      some mammalian CREs are finely tuned by evolution and function through complex,
      nonadditive interactions between bound TFs. CRE-seq will be an important tool to
      uncover the rules that govern these interactions.

PMID- 23129660
TI  - SGTA antagonizes BAG6-mediated protein triage.
AB  - The BAG6 complex was first identified as an upstream loading factor for tail
      anchored membrane proteins entering the TRC40-dependent pathway for
      posttranslational delivery to the endoplasmic reticulum. Subsequently, BAG6 was
      shown to enhance the proteasomal degradation of mislocalized proteins by
      selectively promoting their ubiquitination. We now show that the BAG6-dependent
      ubiquitination of mislocalized proteins is completely reversible and identify a
      pivotal role for the small glutamine-rich tetratricopeptide repeat-containing
      protein alpha (SGTA) in specifically antagonizing this process. SGTA does not
      simply mask the exposed hydrophobic transmembrane domain of a mislocalized
      protein, thereby preventing BAG6 recruitment. Rather, SGTA actively promotes the
      deubiquitination of mislocalized proteins that are already covalently modified,
      thus reversing the actions of BAG6 and inhibiting its capacity to promote
      substrate-specific degradation. This SGTA-mediated effect is independent of its
      tetratricopeptide motifs, suggesting it does not require the actions of Hsp70 and
      Hsp90 chaperones. These data reveal that, in a cellular context, mislocalized
      protein ubiquitination is the result of a dynamic equilibrium reflecting
      competition between pathways that promote either protein maturation or
      degradation. The targeted perturbation of this equilibrium, achieved by
      increasing steady-state SGTA levels, results in a specific stabilization of a
      model mislocalized protein derived from the amyloid precursor protein, an effect
      that is completely negated by ensuring efficient precursor delivery to the
      endoplasmic reticulum. We speculate that a BAG6/SGTA cycle operates during
      protein maturation and quality control in the cytosol and that together these
      components dictate the fate of a specific subset of newly synthesized proteins.

PMID- 23129661
TI  - Conductivity of an atomically defined metallic interface.
AB  - A mechanically formed electrical nanocontact between gold and tungsten is a
      prototypical junction between metals with dissimilar electronic structure.
      Through atomically characterized nanoindentation experiments and first-principles
      quantum transport calculations, we find that the ballistic conduction across this
      intermetallic interface is drastically reduced because of the fundamental
      mismatch between s wave-like modes of electron conduction in the gold and d wave
      like modes in the tungsten. The mechanical formation of the junction introduces
      defects and disorder, which act as an additional source of conduction losses and
      increase junction resistance by up to an order of magnitude. These findings apply
      to nanoelectronics and semiconductor device design. The technique that we use is
      very broadly applicable to molecular electronics, nanoscale contact mechanics,
      and scanning tunneling microscopy.

PMID- 23129662
TI  - Quantifying transient binding of ISWI chromatin remodelers in living cells by
      pixel-wise photobleaching profile evolution analysis.
AB  - Interactions between nuclear proteins and chromatin frequently occur on the time
      scale of seconds and below. These transient binding events are important for the
      fast identification of target sites as concluded from our previous analysis of
      the human chromatin remodelers Snf2H and Snf2L from the imitation switch (ISWI)
      family. Both ATP-driven molecular motor proteins are able to translocate
      nucleosomes along the DNA and appear to exert this activity only on a small
      number of nucleosomes to which they bind more tightly. For mechanistic studies,
      one needs to distinguish such translocation reactions or other long-lived
      interactions associated with conformational changes and/or ATP hydrolysis from
      nonproductive chromatin sampling during target search. These processes can be
      separated by measuring the duration of nucleosome binding with subsecond time
      resolution. To reach this goal, we have developed a fluorescence bleaching
      technique termed pixel-wise photobleaching profile evolution analysis (3PEA). It
      exploits the inherent time structure of confocal microscopy images and yields
      millisecond resolution. 3PEA represents a generally applicable approach to
      quantitate transient chromatin interactions in the 2- to 500-ms time regime
      within only ~1 s needed for a measurement. The green autofluorescent protein
      (GFP)-tagged Snf2H and Snf2L and the inactive Snf2L+13 splice variant were
      studied by 3PEA in comparison to the isolated GFP or red autofluorescent protein
      and a GFP pentamer. Our results reveal that the residence time for transient
      chromatin binding of Snf2H and Snf2L is <2 ms, and strongly support the view that
      ISWI-type remodelers are only rarely active in unperturbed cells during G1 phase.

PMID- 23129663
TI  - Estradiol supports in vitro development of bovine early antral follicles.
AB  - Antrum formation and estradiol (E(2)) secretion are specific features of oocyte
      and granulosa cell complexes (OGCs). This study investigates the effect of E(2)
      on the in vitro development of bovine OGCs derived from early antral follicles as
      well as on the expression of genes in granulosa cells (GCs). The supplementation
      of culture medium with either E(2) or androstenedione (A(4)) improved the in
      vitro development of OGCs and the nuclear maturation of enclosed oocytes. When
      OGCs were cultured in medium containing A(4), developmentally competent OGCs
      secreted more E(2) than OGCs that were not competent. In addition, fulvestrant
      inhibited the effect of both E(2) and A(4) on OGCs development. Comprehensive
      gene expression analysis using next-generation sequence technology was conducted
      for the following three types of GCs: i) GCs of OGCs cultured for 4 days with
      E(2) (1 MUg/ml; E(2)(+)), ii) GCs of OGCs cultured for 4 days without E(2) (E(2)(
      )) or iii) OGCs that formed clear antrum after 8 days of in vitro culture in
      medium containing E(2) (1 MUg/ml; AF group). GCs of the E(2)(+) group had a
      similar gene expression profile to the profile reported previously for the in
      vivo development of large follicles. This genetic profile included factors
      implicated in the up-regulation of E(2) biosynthesis and down-regulation of
      cytoskeleton and extracellular matrices. In addition, a novel gene expression
      profile was found in the AF group. In conclusion, E(2) impacts the gene
      expression profile of GCs to support the in vitro development of OGCs.

PMID- 23129664
TI  - A sampler from spending to system transformation.

PMID- 23129665
TI  - Many accountable care organizations are now up and running, if not off to the
      races.

PMID- 23129666
TI  - A framework for evaluating the formation, implementation, and performance of
      accountable care organizations.
AB  - The implementation of accountable care organizations (ACOs), a new health care
      payment and delivery model designed to improve care and lower costs, is
      proceeding rapidly. We build on our experience tracking early ACOs to identify
      the major factors-such as contract characteristics; structure, capabilities, and
      activities; and local context-that would be likely to influence ACO formation,
      implementation, and performance. We then propose how an ACO evaluation program
      could be structured to guide policy makers and payers in improving the design of
      ACO contracts, while providing insights for providers on approaches to care
      transformation that are most likely to be successful in different contexts. We
      also propose key activities to support evaluation of ACOs in the near term,
      including tracking their formation, developing a set of performance measures
      across all ACOs and payers, aggregating those performance data, conducting
      qualitative and quantitative research, and coordinating different evaluation
      activities.

PMID- 23129667
TI  - A collaborative accountable care model in three practices showed promising early
      results on costs and quality of care.
AB  - Cigna's Collaborative Accountable Care initiative provides financial incentives
      to physician groups and integrated delivery systems to improve the quality and
      efficiency of care for patients in commercial open-access benefit plans.
      Registered nurses who serve as care coordinators employed by participating
      practices are a central feature of the initiative. They use patient-specific
      reports and practice performance reports provided by Cigna to improve care
      coordination, identify and close care gaps, and address other opportunities for
      quality improvement. We report interim quality and cost results for three
      geographically and structurally diverse provider practices in Arizona, New
      Hampshire, and Texas. Although not statistically significant, these early results
      revealed favorable trends in total medical costs and quality of care, suggesting
      that a shared-savings accountable care model and collaborative support from the
      payer can enable practices to take meaningful steps toward full accountability
      for care quality and efficiency.

PMID- 23129668
TI  - An academic health center sees both challenges and enabling forces as it creates
      an accountable care organization.
AB  - Health care reform presents academic health centers with an opportunity to test
      new systems of care, such as accountable care organizations (ACOs), that are
      intended to improve patients' health and well-being, mitigate the anticipated
      shortage in primary care providers, and bend the cost curve. In its ongoing
      efforts to develop an ACO, the Robert Wood Johnson Medical School, an academic
      health center, has found helpful a rapidly evolving competitive environment and
      insurers willing to experiment with new models of care. But the center has also
      encountered six types of barriers: conceptual, financial, cultural, regulatory,
      organizational, and historical. How this academic health center has faced these
      barriers offers valuable lessons to other health systems engaged in creating
      ACOs.

PMID- 23129669
TI  - Insights from transformations under way at four Brookings-Dartmouth accountable
      care organization pilot sites.
AB  - This cross-site comparison of the early experience of four provider organizations
      participating in the Brookings-Dartmouth Accountable Care Organization
      Collaborative identifies factors that sites perceived as enablers of successful
      ACO formation and performance. The four pilots varied in size, with between 7,000
      and 50,000 attributed patients and 90 to 2,700 participating physicians. The
      sites had varying degrees of experience with performance-based payments; however,
      all formed collaborative new relationships with payers and created shared savings
      agreements linked to performance on quality measures. Each organization devoted
      major efforts to physician engagement. Policy makers now need to consider how to
      support and provide incentives for the successful formation of multipayer ACOs,
      and how to align private-sector and CMS performance measures. Linking providers
      to learning networks where payers and providers can address common technical
      issues could help. These sites' transitions to the new payment model constitutes
      an ongoing journey that will require continual adaptation in the structure of
      contracts and organizational attributes.

PMID- 23129670
TI  - Accountable care organizations may have difficulty avoiding the failures of
      integrated delivery networks of the 1990s.
AB  - Accountable care organizations are intended to improve the quality and lower the
      cost of health care through several mechanisms, such as disease management
      programs, care coordination, and aligning financial incentives for hospitals and
      physicians. Providers employed several of these mechanisms in forming the
      integrated delivery networks of the 1990s. The networks failed, however, because
      of heavy financial losses stemming from hospitals' purchase of physician
      practices and their inability to align incentives, garner capitated contracts,
      and develop the infrastructure to manage risk. Although the current mechanisms
      underlying accountable care organizations continue to evolve, whether and how
      they will have an impact on quality and costs remains open to question. Care
      coordination and information technology are proving more complicated and
      expensive to implement than anticipated, providers may lack the ability to
      implement these mechanisms, and primary care providers are in short supply. As in
      the 1990s, success depends on targeting specific populations, such as people with
      multiple chronic conditions who need and may benefit from coordinated care.

PMID- 23129671
TI  - Small primary care practices face four hurdles--including a physician-centric
      mind-set--in becoming medical homes.
AB  - Transforming small independent practices to patient-centered medical homes is
      widely believed to be a critical step in reforming the US health care system. Our
      team has conducted research on improving primary care practices for more than
      fifteen years. We have found four characteristics of small primary care practices
      that seriously inhibit their ability to make the transformation to this new care
      model. We found that small practices were extremely physician-centric, lacked
      meaningful communication among physicians, were dominated by authoritarian
      leadership behavior, and were underserved by midlevel clinicians who had been
      cast into unimaginative roles. Our analysis suggests that in addition to payment
      reform, a shift in the mind-set of primary care physicians is needed. Unless
      primary care physicians can adopt new mental models and think in new ways about
      themselves and their practices, it will be very difficult for them and their
      practices to create innovative care teams, become learning organizations, and act
      as good citizens within the health care neighborhood.

PMID- 23129672
TI  - Results from a patient-centered medical home pilot at UPMC Health Plan hold
      lessons for broader adoption of the model.
AB  - The patient-centered medical home is a promising model for improving access to
      high-quality care for more Americans at lower cost. However, feasible pathways
      for achieving a transformation from current primary care practices to this new
      model have yet to be fully identified. We report on the experience of UPMC Health
      Plan-part of a large, integrated delivery and financing system headquartered in
      Pittsburgh, Pennsylvania-in its efforts to support primary care practices as they
      converted to patient-centered medical homes. From 2008 through 2010, sites
      participating in the UPMC pilot achieved lower medical and pharmacy costs; more
      efficient service delivery, such as lower hospital admissions and readmissions
      and less use of hospital emergency departments; and a 160 percent return on the
      plan's investment when compared with nonparticipating sites. We suggest
      approaches that could spur the adoption and spread of the model, including that
      payers be offered incentives to enter into patient-centered medical home
      contracts with interested providers; that payers increase efforts to provide
      primary care practices with access to usable data on their patient populations;
      and that telehealth be instituted to connect care managers to patients and
      practices when in-person visits are not possible or necessary.

PMID- 23129673
TI  - About half of the states are implementing patient-centered medical homes for
      their Medicaid populations.
AB  - Public and private payers are testing the patient-centered medical home model by
      shifting resources to enhance primary care as an important component of improving
      the quality and cost-effectiveness of the US health care delivery system.
      Medicaid has been at the forefront of this movement. Since 2006 twenty-five
      states have implemented new payment systems or revised existing ones so that
      primary care providers can function as patient-centered medical homes. State
      Medicaid programs are taking a variety of approaches. For example, Minnesota's
      reforms focus on chronically ill populations, while in Missouri a 90 percent
      federal match under the Affordable Care Act is helping integrate primary and
      behavioral health care and address issues of long-term services and supports.
      These reforms have led to better alignment of payments with performance metrics
      that emphasize health outcomes, patient satisfaction, and cost containment. This
      article focuses on trends in Medicaid patient-centered medical home payment that
      can inform public and private payment strategies more broadly.

PMID- 23129674
TI  - The 'Global Outcomes Score': a quality measure, based on health outcomes, that
      compares current care to a target level of care.
AB  - The quality of health care is measured today using performance measures that
      calculate the percentage of people whose health conditions are managed according
      to specified processes or who meet specified treatment goals. This approach has
      several limitations. For instance, each measure looks at a particular process,
      risk factor, or biomarker one by one, and each uses sharp thresholds for defining
      "success" versus "failure." We describe a new measure of quality called the
      Global Outcomes Score (GO Score), which represents the proportion of adverse
      outcomes expected to be prevented in a population under current levels of care
      compared to a target level of care, such as 100 percent performance on certain
      clinical guidelines. We illustrate the use of the GO Score to measure blood
      pressure and cholesterol care in a longitudinal study of people at risk of
      atherosclerotic diseases, or hardening of the arteries. In that population the
      baseline GO Score was 40 percent, which indicates that the care being delivered
      was 40 percent as effective in preventing myocardial infarctions and strokes as
      our target level of care. The GO Score can be used to assess the potential
      effectiveness of different interventions such as prevention activities, tests,
      and treatments.

PMID- 23129675
TI  - David Eddy created the Archimedes model to predict and analyze care.

PMID- 23129676
TI  - Physicians with the least experience have higher cost profiles than do physicians
      with the most experience.
AB  - Health plans and Medicare are using cost profiles to identify which physicians
      account for more health care spending than others. By identifying the costliest
      physicians, health plans and Medicare hope to craft policy interventions to
      reduce total health care spending. To identify which physician types, if any,
      might be costlier than others, we analyzed cost profiles created from health plan
      claims for physicians in Massachusetts. We found that physicians with fewer than
      ten years of experience had 13.2 percent higher overall costs than physicians
      with forty or more years of experience. We found no association between costs and
      other physician characteristics, such as having had malpractice claims or
      disciplinary actions, board certification status, and the size of the group in
      which the physician practices. Although winners and losers are inevitable in any
      cost-profiling effort, physicians with less experience are more likely to be
      negatively affected by policies that use cost profiles, unless they change their
      practice patterns. For example, these physicians could be excluded from high
      value networks or receive lower payments under Medicare's planned value-based
      payment program. We cannot fully explain the mechanism by which more-experienced
      physicians have lower costs, but our results suggest that the more costly
      practice style of newly trained physicians may be a driver of rising health care
      costs overall.

PMID- 23129677
TI  - State unemployment in recessions during 1991-2009 was linked to faster growth in
      Medicare spending.
AB  - During the US recession of 2007-09, overall health care spending growth fell, but
      Medicare spending growth increased. Using state-level data from the period 1991
      2009, we show that these divergent trends were also observed within states.
      Furthermore, increases in state unemployment rates were associated with higher
      Medicare spending per capita and increased hospital use by Medicare
      beneficiaries. For example, a one-percentage-point point rise in the unemployment
      rate was associated with a $40 (0.7 percent) increase in Medicare spending per
      capita. Our results suggest that economic downturns contribute to Medicare
      spending and use. One of many possible explanations may be that health care
      providers have greater capacity, inclination, and financial incentive to treat
      Medicare patients during recessions as a result of slackening demand from the non
      Medicare population.

PMID- 23129678
TI  - Ten modifiable health risk factors are linked to more than one-fifth of employer
      employee health care spending.
AB  - An underlying premise of the Affordable Care Act provisions that encourage
      employers to adopt health promotion programs is an association between workers'
      modifiable health risks and increased health care costs. Employers, consultants,
      and vendors have cited risk-cost estimates developed in the 1990s and wondered
      whether they still hold true. Examining ten of these common health risk factors
      in a working population, we found that similar relationships between such risks
      and total medical costs documented in a widely cited study published in 1998
      still hold. Based on our sample of 92,486 employees at seven organizations over
      an average of three years, $82,072,456, or 22.4 percent, of the $366,373,301
      spent annually by the seven employers and their employees in the study was
      attributed to the ten risk factors studied. This amount was similar to almost a
      quarter of spending linked to risk factors (24.9 percent) in the 1998 study. High
      risk for depression remained most strongly associated with increased per capita
      annual medical spending (48 percent, or $2,184, higher). High blood glucose, high
      blood pressure, and obesity were strongly related to increased health care costs
      (31.8 percent, 31.6 percent, and 27.4 percent higher, respectively), as were
      tobacco use, physical inactivity, and high stress. These findings indicate
      ongoing opportunities for well-designed and properly targeted employer-sponsored
      health promotion programs to produce substantial savings.

PMID- 23129679
TI  - A new tool to give hospitalists feedback to improve interprofessional teamwork
      and advance patient care.
AB  - Teamwork is a vital skill for health care professionals, but the fragmented
      systems within which they work frequently do not recognize or support good
      teamwork. The American Board of Internal Medicine has developed and is testing
      the Teamwork Effectiveness Assessment Module (TEAM), a tool for physicians to
      evaluate how they perform as part of an interprofessional patient care team. The
      assessment provides hospitalist physicians with feedback data drawn from their
      own work of caring for patients, in a way that is intended to support immediate,
      concrete change efforts to improve the quality of patient care. Our approach
      demonstrates the value of looking at teamwork in the real world of health care
      that is, as it occurs in the actual contexts in which providers work together to
      care for patients. The assessment of individual physicians' teamwork competencies
      may play a role in the larger effort to bring disparate health professions
      together in a system that supports and rewards a team approach in hope of
      improving patient care.

PMID- 23129680
TI  - In the Netherlands, rich interaction among professionals conducting disease
      management led to better chronic care.
AB  - Disease management programs based on the Chronic Care Model are expected to
      improve the quality of chronic care delivery. However, evidence to date for such
      improvement and how it is achieved is scarce. In 2010 and again in 2011, we
      surveyed professionals in twenty-two primary care practices in the Netherlands
      that had implemented the Chronic Care Model of disease management beginning in
      2009. The responses showed that, over time, chronic illness care delivery
      improved to advanced levels. The gains were attributed primarily to improved
      relational coordination-that is, raising the quality of communication and task
      integration among professionals from diverse disciplines who share common
      objectives. These findings may have implications for other disease management
      efforts by collaborative care teams, in that they suggest that diverse health
      care professionals must be strongly connected to provide effective, holistic
      care.

PMID- 23129681
TI  - The longer the shifts for hospital nurses, the higher the levels of burnout and
      patient dissatisfaction.
AB  - Extended work shifts of twelve hours or longer are common and even popular with
      hospital staff nurses, but little is known about how such extended hours affect
      the care that patients receive or the well-being of nurses. Survey data from
      nurses in four states showed that more than 80 percent of the nurses were
      satisfied with scheduling practices at their hospital. However, as the proportion
      of hospital nurses working shifts of more than thirteen hours increased,
      patients' dissatisfaction with care increased. Furthermore, nurses working shifts
      of ten hours or longer were up to two and a half times more likely than nurses
      working shorter shifts to experience burnout and job dissatisfaction and to
      intend to leave the job. Extended shifts undermine nurses' well-being, may result
      in expensive job turnover, and can negatively affect patient care. Policies
      regulating work hours for nurses, similar to those set for resident physicians,
      may be warranted. Nursing leaders should also encourage workplace cultures that
      respect nurses' days off and vacation time, promote nurses' prompt departure at
      the end of a shift, and allow nurses to refuse to work overtime without
      retribution.

PMID- 23129682
TI  - Supplemental nurses are just as educated, slightly less experienced, and more
      diverse compared to permanent nurses.
AB  - In the past three decades, the shortage of nurses willing to work in hospitals
      has been a persistent challenge in the United States. Hiring supplemental
      registered nurses-nurses on short-term contracts obtained through an external
      staffing agency-has been common to fill gaps in nurse staffing. But there has
      been insufficient evidence about supplemental nurse workforce trends to inform
      workforce policy. To address this concern, we compared qualifications and
      characteristics of supplemental nurses with those of permanent nurses during 1984
      2008. The two groups shared similar education levels in terms of possessing a
      baccalaureate or higher degree. Supplemental nurses were somewhat less
      experienced than permanent nurses, averaging fifteen years of experience in 2008
      compared to eighteen years for permanent nurses. The supplemental nurse workforce
      was more diverse racially and ethnically and more likely to be male than the
      permanent nurse workforce. These data show that employing supplemental nurses
      could help meet the challenges of an aging nursing workforce, the projected
      future shortage of nurses, and an increasingly diverse US population.

PMID- 23129684
TI  - Proposed 'grant-and-access' program with price caps could stimulate development
      of drugs for very rare diseases.
AB  - The 1983 Orphan Drug Act created incentives for the development of orphan drugs.
      Despite its successes, including a substantial increase in new drugs, approved
      orphan drugs still treat fewer than 5 percent of registered rare diseases. In
      addition, concerns have arisen about the high prices of many of these therapies,
      which can cost hundreds of thousands of dollars per patient each year. In this
      article, we propose a new "grant-and-access pathway," in which drug developers
      could opt to compete for federal grants to subsidize the costs of clinical
      testing. In return for the grant funding, companies would no longer claim orphan
      drug tax credits and would agree to price caps for marketed products based on the
      duration and costs associated with drug development, expected market size, and
      target rate of return. We identify scenarios in which such a policy could provide
      a net benefit to society.

PMID- 23129683
TI  - Success of program linking data sources to monitor H1N1 vaccine safety points to
      potential for even broader safety surveillance.
AB  - In response to the 2009 H1N1 pandemic and subsequent vaccination program, the
      Department of Health and Human Services and collaborators developed the Post
      Licensure Rapid Immunization Safety Monitoring (PRISM) Program as a demonstration
      project to detect rare adverse events rapidly. The program monitored three
      million people who had received the H1N1 vaccine by linking data from large
      private health plans and from public immunization registries that had originally
      not been designed to share data, and on a larger scale than had been previously
      attempted. The program generated safety data in two weeks rather than three to
      six monty 10ths-the standard time frame achievable using health plan data. PRISM
      substantially contributed to the understanding of the safety of H1N1 vaccines.
      Its use in the case of H1N1 highlights the necessity of proactive planning,
      scalable infrastructure, and public-private partnerships in tracking adverse
      events after vaccination in epidemics. It also illustrates how data could be
      integrated to produce policy-relevant information for other medical products.

PMID- 23129685
TI  - Early results of China's historic health reforms: the view from minister Chen
      Zhu. Interview by Tsung-Mei Cheng.

PMID- 23129686
TI  - To save children's lives, China should adopt an initiative to speed introduction
      of pneumonia vaccines.
AB  - Despite rapid economic development, China has not yet incorporated into its
      national childhood immunization program vaccines against Streptococcus pneumoniae
      and Haemophilus influenzae type b. Both vaccines can prevent pneumonia, the
      leading infectious disease killer of young children in China. In contrast, the
      other World Health Organization member nations with the ten largest birth cohorts
      have included H. influenzae type b in their national childhood immunization
      programs, and many of the world's wealthiest and poorest countries have done the
      same with S. pneumoniae. In this article we review what is known about S.
      pneumoniae and H. influenzae type b in China, and we make recommendations for how
      to accelerate the use of vaccines against these pathogens in that country. We
      propose that China adopt a "Chinese Accelerated Vaccine Initiative" modeled after
      other successful global programs. This broad effort would marshal the evidence
      and commitment needed to change vaccine policy, then develop and implement a plan
      for a sustainable, affordable supply of these and other new vaccines.

PMID- 23129687
TI  - A nurse learns firsthand that you may fend for yourself after a hospital stay.

PMID- 23129688
TI  - New York State Health Foundation grant helps health centers win federal expansion
      funds.
AB  - With approximately 1.2 million New Yorkers poised to gain health insurance
      coverage as a result of federal health reform, demand for primary care services
      is likely to increase greatly. The Affordable Care Act includes $11 billion in
      funding to enhance primary care access at community health centers. Recognizing a
      need and an opportunity, in August 2010 the New York State Health Foundation made
      a grant of nearly $400,000 to the Community Health Care Association of New York
      State to work with twelve health centers to develop successful proposals for
      obtaining and using these federal funds. Ultimately, eleven of the twelve sites
      are expected to receive $25.6 million in federal grants over a five-year period-a
      sixty-four-fold return on the foundation's investment. This article describes the
      strategy for investing in community health centers; identifies key project
      activities, challenges, and lessons; and highlights its next steps for
      strengthening primary care.

PMID- 23129690
TI  - The failures of the mental health system.

PMID- 23129692
TI  - Medical spending and global budgets.

PMID- 23129693
TI  - Nurses for patient-centered medical homes.

PMID- 23129695
TI  - Health-related quality of life of preschool caregivers in Hong Kong.
AB  - The aim of this study was to explore the health-related quality of life (HRQOL)
      of preschool caregivers in Hong Kong with a view to informing policy-makers about
      health promotion within this population. The following research questions were
      addressed: (i) What was the HRQOL of young children's caregivers in Hong Kong?
      (ii) Were there differences between these caregivers' health and the general Hong
      Kong population's health? (iii) What demographic factors were related to these
      caregivers' quality of life? Mixed methods research, including quantitative and
      qualitative tools, was utilized. Data from a study consisted of a survey of 834
      preschool caregivers along with 3 in-depth interviews with employees of
      kindergarten-cum-childcare centres from different socio-economic groups within
      the city of Hong Kong. An HRQOL questionnaire (the SF-36 v. 1), together with
      demographic characteristics and illness/disease incidence data, were collected.
      The results suggested that the Hong Kong preschool caregivers had a substantially
      poorer HRQOL than Hong Kong's general population. The analysis found that young
      caregivers and caregivers with young families had a significantly lower HRQOL
      than more senior caregivers. They tended to feel tired, lacked energy and failed
      to perform vigorous activities. Significant differences were also found according
      to the caregivers' socio-economic status. Health and education policy-makers
      should note that young children's caregivers are in a serious state of ill
      health. Further health education and promotion efforts should target this
      population. 

PMID- 23129696
TI  - Antihypertensive effects of exercise among those with resistant hypertension.

PMID- 23129697
TI  - Explaining socioeconomic inequalities in childhood blood pressure and
      prehypertension: the ABCD study.
AB  - Much remains to be understood about the socioeconomic inequalities in
      hypertension that continue to exist. We investigated the association of
      socioeconomic status with blood pressure and prehypertension in childhood. In a
      prospective cohort, 3024 five- to six-year-old children had blood pressure
      measurements and available information on potential explanatory factors, namely
      birth weight, gestational age, smoking during pregnancy, pregnancy-induced
      hypertension, familial hypertension, maternal body mass index, breastfeeding
      duration, domestic tobacco exposure, and body mass index. The systolic and
      diastolic blood pressures of children from mid-educated women were 1.0-mm Hg
      higher (95% CI, 0.4-1.7) and 0.9-mm Hg higher (95% CI, 0.3-1.4), and the blood
      pressures of children with low-educated women were 2.2-mm Hg higher (95% CI, 1.4
      3.0) and 1.7-mm Hg higher (95% CI, 1.1-2.4) compared with children with high
      educated women. Children with mid- (odds ratio, 1.50; 95% CI, 1.18-1.92) or low
      educated mothers (odds ratio, 1.80; 95% CI, 1.35-2.42) were more likely to have
      prehypertension compared with children with high-educated mothers. Using path
      analyses, birth weight, breastfeeding duration, and body mass index were
      determined as having a role in the association of maternal education with
      offspring blood pressure and prehypertension. The socioeconomic gradient in
      hypertension appears to emerge from childhood as the results show a higher blood
      pressure and more prehypertension in children from lower socioeconomic status
      families. Socioeconomic disparities could be reduced by improving 3 factors in
      particular, namely birth weight, breastfeeding duration, and body mass index, but
      other factors might also play a role.

PMID- 23129698
TI  - The beta3 subunit contributes to vascular calcium channel upregulation and
      hypertension in angiotensin II-infused C57BL/6 mice.
AB  - Voltage-gated L-type Ca(2+) (Ca(v)1.2) channels in vascular smooth muscle cells
      are a predominant Ca(2+) influx pathway that mediates arterial tone. Channel
      biogenesis is accomplished when the pore-forming alpha(1C) subunit coassembles
      with regulatory Ca(v)beta subunits intracellularly, and the multiprotein Ca(v)1.2
      channel complex translocates to the plasma membrane to form functional Ca(2+)
      channels. We hypothesized that the main Ca(v)beta isoform in vascular smooth
      muscle cells, Ca(v)beta3, is required for the upregulation of arterial Ca(v)1.2
      channels during the development of hypertension, an event associated with
      abnormal Ca(2+)-dependent tone. Ca(v)1.2 channel expression and function were
      compared between second-order mesenteric arteries of C57BL/6 wild-type (WT) and
      Ca(v)beta3(-/-) mice infused with saline (control) or angiotensin II (Ang II) for
      2 weeks to induce hypertension. The mesenteric arteries of Ang II-infused WT mice
      showed increased Ca(v)1.2 channel expression and accentuated Ca(2+)-mediated
      contractions compared with saline-infused WT mice. In contrast, Ca(v)1.2 channels
      failed to upregulate in mesenteric arteries of Ang II-infused Ca(v)beta3(-/-)
      mice, and Ca(2+)-dependent reactivity was normal in these arteries. Basal
      systolic blood pressure was not significantly different between WT and
      Ca(v)beta3(-/-) mice (98 +/- 2 and 102 +/- 3 mm Hg, respectively), but the
      Ca(v)beta3(-/-) mice showed a blunted pressor response to Ang II infusion. Two
      weeks after the start of Ang II administration, the systolic blood pressure of
      Ca(v)beta3(-/-) mice averaged 149 +/- 4 mm Hg compared with 180 +/- 5 mm Hg in WT
      mice. Thus, the Ca(v)beta3 subunit is a critical regulatory protein required to
      upregulate arterial Ca(v)1.2 channels and fully develop Ang II-dependent
      hypertension in C57BL/6 mice.

PMID- 23129699
TI  - Novel peptide isomer strategy for stable inhibition of catecholamine release:
      application to hypertension.
AB  - Although hypertension remains the most potent and widespread cardiovascular risk
      factor, its pharmacological treatment has achieved only limited success. The
      chromogranin A-derived fragment catestatin inhibits catecholamine release by
      acting as an endogenous nicotinic cholinergic antagonist and can rescue
      hypertension in the setting of chromogranin A-targeted ablation. Here, we
      undertook novel peptide chemistry to synthesize isomers of catestatin:
      normal/wild-type as well as a retro-inverso (R-I) version, with not only
      inversion of chirality (L -> D amino acids) but also reversal of sequence
      (carboxyl -> amino). The R-I peptide was entirely resistant to proteolytic
      digestion and displayed enhanced potency as well as preserved specificity of
      action toward nicotinic cholinergic events: catecholamine secretion, agonist
      desensitization, secretory protein transcription, and cationic signal
      transduction. Structural modeling suggested similar side-chain orientations of
      the wild-type and R-I isomers, whereas circular dichroism spectroscopy documented
      inversion of chirality. In vivo, the R-I peptide rescued hypertension in 2 mouse
      models of the human trait: monogenic chromogranin A-targeted ablation, with
      prolonged efficacy of the R-I version and a polygenic model, with magnified
      efficacy of the R-I version. These results may have general implications for
      generation of metabolically stable mimics of biologically active peptides for
      cardiovascular pathways. The findings also point the way toward a potential new
      class of drug therapeutics for an important risk trait and, more generally, open
      the door to broader applications of the R-I strategy in other pathways involved
      in cardiovascular biology, with the potential for synthesis of diagnostic and
      therapeutic probes for both physiology and disease.

PMID- 23129701
TI  - Role of policy and government in the obesity epidemic.

PMID- 23129702
TI  - Diastolic dysfunction and risk of atrial fibrillation: a mechanistic appraisal.

PMID- 23129700
TI  - Outcome-driven thresholds for home blood pressure measurement: international
      database of home blood pressure in relation to cardiovascular outcome.
AB  - The lack of outcome-driven operational thresholds limits the clinical application
      of home blood pressure (BP) measurement. Our objective was to determine an
      outcome-driven reference frame for home BP measurement. We measured home and
      clinic BP in 6470 participants (mean age, 59.3 years; 56.9% women; 22.4% on
      antihypertensive treatment) recruited in Ohasama, Japan (n=2520); Montevideo,
      Uruguay (n=399); Tsurugaya, Japan (n=811); Didima, Greece (n=665); and nationwide
      in Finland (n=2075). In multivariable-adjusted analyses of individual subject
      data, we determined home BP thresholds, which yielded 10-year cardiovascular
      risks similar to those associated with stages 1 (120/80 mm Hg) and 2 (130/85 mm
      Hg) prehypertension, and stages 1 (140/90 mm Hg) and 2 (160/100 mm Hg)
      hypertension on clinic measurement. During 8.3 years of follow-up (median), 716
      cardiovascular end points, 294 cardiovascular deaths, 393 strokes, and 336
      cardiac events occurred in the whole cohort; in untreated participants these
      numbers were 414, 158, 225, and 194, respectively. In the whole cohort, outcome
      driven systolic/diastolic thresholds for the home BP corresponding with stages 1
      and 2 prehypertension and stages 1 and 2 hypertension were 121.4/77.7,
      127.4/79.9, 133.4/82.2, and 145.4/86.8 mm Hg; in 5018 untreated participants,
      these thresholds were 118.5/76.9, 125.2/79.7, 131.9/82.4, and 145.3/87.9 mm Hg,
      respectively. Rounded thresholds for stages 1 and 2 prehypertension and stages 1
      and 2 hypertension amounted to 120/75, 125/80, 130/85, and 145/90 mm Hg,
      respectively. Population-based outcome-driven thresholds for home BP are slightly
      lower than those currently proposed in hypertension guidelines. Our current
      findings could inform guidelines and help clinicians in diagnosing and managing
      patients.

PMID- 23129703
TI  - Catheter-induced venous spasm.

PMID- 23129704
TI  - Characterization of cardiac sarcoma with 2- and 3-dimensional echocardiography,
      myocardial contrast echocardiography and cardiac magnetic resonance imaging.

PMID- 23129706
TI  - Letter by Sacha regarding article, "clinical and genetic determinants of torsade
      de pointes risk".

PMID- 23129707
TI  - A strategy for UK marine science for the next 20 years.

PMID- 23129708
TI  - A strategy for UK marine science for the next 20 years.

PMID- 23129709
TI  - Changing currents: a strategy for understanding and predicting the changing ocean
      circulation.
AB  - Within the context of UK marine science, we project a strategy for ocean
      circulation research over the next 20 years. We recommend a focus on three types
      of research: (i) sustained observations of the varying and evolving ocean
      circulation, (ii) careful analysis and interpretation of the observed climate
      changes for comparison with climate model projections, and (iii) the design and
      execution of focused field experiments to understand ocean processes that are not
      resolved in coupled climate models so as to be able to embed these processes
      realistically in the models. Within UK-sustained observations, we emphasize
      smart, cost-effective design of the observational network to extract maximum
      information from limited field resources. We encourage the incorporation of new
      sensors and new energy sources within the operational environment of UK-sustained
      observational programmes to bridge the gap that normally separates laboratory
      prototype from operational instrument. For interpreting the climate-change
      records obtained through a variety of national and international sustained
      observational programmes, creative and dedicated UK scientists should lead
      efforts to extract the meaningful signals and patterns of climate change and to
      interpret them so as to project future changes. For the process studies,
      individual scientists will need to work together in team environments to combine
      observational and process modelling results into effective improvements in the
      coupled climate models that will lead to more accurate climate predictions.

PMID- 23129710
TI  - A perspective on the future of physical oceanography.
AB  - The ocean flows because it is forced by winds, tides and exchanges of heat and
      freshwater with the overlying atmosphere and cryosphere. To achieve a state where
      the defining properties of the ocean (such as its energy and momentum) do not
      continuously increase, some form of dissipation or damping is required to balance
      the forcing. The ocean circulation is thought to be forced primarily at the large
      scales characteristic of ocean basins, yet to be damped at much smaller scales
      down to those of centimetre-sized turbulence. For decades, physical
      oceanographers have sought to comprehend the fundamentals of this fractal puzzle:
      how the ocean circulation is driven, how it is damped and how ocean dynamics
      connects the very different scales of forcing and dissipation. While in the last
      two decades significant advances have taken place on all these three fronts, the
      thrust of progress has been in understanding the driving mechanisms of ocean
      circulation and the ocean's ensuing dynamical response, with issues surrounding
      dissipation receiving comparatively little attention. This choice of research
      priorities stems not only from logistical and technological difficulties in
      observing and modelling the physical processes responsible for damping the
      circulation, but also from the untested assumption that the evolution of the
      ocean's state over time scales of concern to humankind is largely independent of
      dissipative processes. In this article, I illustrate some of the key advances in
      our understanding of ocean circulation that have been achieved in the last 20
      years and, based on a range of evidence, contend that the field will soon reach a
      stage in which uncertainties surrounding the arrest of ocean circulation will
      pose the main challenge to further progress. It is argued that the role of the
      circulation in the coupled climate system will stand as a further focal point of
      major advances in understanding within the next two decades, supported by the
      drive of physical oceanography towards a more operational enterprise by
      contextual factors. The basic elements that a strategy for the future must have
      to foster progress in these two areas are discussed, with an overarching emphasis
      on the promotion of curiosity-driven fundamental research against opposing
      external pressures and on the importance of upholding fundamental research as the
      apex of education in the field.

PMID- 23129711
TI  - Ice sheets viewed from the ocean: the contribution of marine science to
      understanding modern and past ice sheets.
AB  - Over the last two decades, marine science, aided by technological advances in
      sediment coring, geophysical imaging and remotely operated submersibles, has
      played a major role in the investigation of contemporary and former ice sheets.
      Notable advances have been achieved with respect to reconstructing the extent and
      flow dynamics of the large polar ice sheets and their mid-latitude counterparts
      during the Quaternary from marine geophysical and geological records of landforms
      and sediments on glacier-influenced continental margins. Investigations of the
      deep-sea ice-rafted debris record have demonstrated that catastrophic collapse of
      large (10(5)-10(6) km(2)) ice-sheet drainage basins occurred on millennial and
      shorter time scales and had a major influence on oceanography. In the last few
      years, increasing emphasis has been placed on understanding physical processes at
      the ice-ocean interface, particularly at the grounding line, and on determining
      how these processes affect ice-sheet stability. This remains a major challenge,
      however, owing to the logistical constraints imposed by working in ice-infested
      polar waters and ice-shelf cavities. Furthermore, despite advances in
      reconstructing the Quaternary history of mid- and high-latitude ice sheets, major
      unanswered questions remain regarding West Antarctic ice-sheet stability, and the
      long-term offshore history of the East Antarctic and Greenland ice sheets remains
      poorly constrained. While these are major research frontiers in glaciology, and
      ones in which marine science has a pivotal role to play, realizing such future
      advances will require an integrated collaborative approach between
      oceanographers, glaciologists, marine geologists and numerical modellers.

PMID- 23129712
TI  - Palaeoceanography: motivations and challenges for the future.
AB  - The ocean interacts with the atmosphere, biosphere and cryosphere in a complex
      way, modulating climate through the storage and transport of heat, nutrients and
      carbon. As such, it is important that we understand the ways in which the ocean
      behaves and the factors that can lead to change. In order to gain this
      understanding, we need to look back into the past, on time scales from recent
      decadal-scale change, through the abrupt changes of the Pleistocene and back to
      times when the Earth's climate was significantly different than the Holocene. A
      key challenge facing the field of palaeoceanography is to combine data and
      modelling in a common framework. Coupling palaeo-data and models should improve
      our knowledge of how the Earth works, and perhaps of more direct societal
      relevance, might enable us to provide better predictive capabilities in climate
      modelling. In this discussion paper, we examine the motivations, past successes
      and challenges facing palaeoceanographic studies. We then suggest a number of
      areas and approaches that we believe will allow palaeoceanography to continue to
      provide new insights into processes that affect future climate change.

PMID- 23129713
TI  - Aspects of marine geoscience: a review and thoughts on potential for observing
      active processes and progress through collaboration between the ocean sciences.
AB  - Much progress has been made in the UK in characterizing the internal structures
      of major physiographic features in the oceans and in developing understanding of
      the geological processes that have created or shaped them. UK researchers have
      authored articles of high impact in all areas described here. In contrast to
      terrestrial geoscience, however, there have been few instrumented observations
      made of active processes by UK scientists. This is an area that could be
      developed over the next decades in the UK. Research on active processes has the
      potential ability to engage the wider public: Some active processes present
      significant geo-hazards to populations and offshore infrastructure that require
      monitoring and there could be commercial applications of technological
      developments needed for science. Some of the suggestions could involve studies in
      shallow coastal waters where ship costs are much reduced, addressing tighter
      funding constraints over the near term. The possibilities of measuring aspects of
      volcanic eruptions, flowing lava, turbidity currents and mass movements
      (landslides) are discussed. A further area of potential development is in greater
      collaboration between the ocean sciences. For example, it is well known in
      terrestrial geomorphology that biological agents are important in modulating
      erosion and the transport of sediments, ultimately affecting the shape of the
      Earth's surface in various ways. The analogous effect of biology on large-scale
      geomorphology in the oceans is also known but remains poorly quantified. Physical
      oceanographic models are becoming increasingly accurate and could be used to
      study further the patterns of erosion, particle transport and deposition in the
      oceans. Marine geological and geophysical data could in turn be useful for
      further verification of such models. Adapting them to conditions of past oceans
      could address the shorter-period movements, such as due to internal waves and
      tides, which have been barely addressed in palaeoceanography.

PMID- 23129714
TI  - Pressures on the marine environment and the changing climate of ocean
      biogeochemistry.
AB  - The oceans are under pressure from human activities. Following 250 years of
      industrial activity, effects are being seen at the cellular through to regional
      and global scales. The change in atmospheric CO(2) from 280 ppm in pre-industrial
      times to 392 ppm in 2011 has contributed to the warming of the upper 700 m of the
      ocean by approximately 0.1 degrees C between 1961 and 2003, to changes in sea
      water chemistry, which include a pH decrease of approximately 0.1, and to
      significant decreases in the sea water oxygen content. In parallel with these
      changes, the human population has been introducing an ever-increasing level of
      nutrients into coastal waters, which leads to eutrophication, and by 2008 had
      resulted in 245,000 km(2) of severely oxygen-depleted waters throughout the
      world. These changes are set to continue for the foreseeable future, with
      atmospheric CO(2) predicted to reach 430 ppm by 2030 and 750 ppm by 2100. The
      cycling of biogeochemical elements has proved sensitive to each of these effects,
      and it is proposed that synergy between stressors may compound this further. The
      challenge, within the next few decades, for the marine science community, is to
      elucidate the scope and extent that biological processes can adapt or acclimatize
      to a changing chemical and physical marine environment.

PMID- 23129715
TI  - Challenges for implementing the Marine Strategy Framework Directive in a climate
      of macroecological change.
AB  - Unprecedented basin-scale ecological changes are occurring in our seas. As
      temperature and carbon dioxide concentrations increase, the extent of sea ice is
      decreasing, stratification and nutrient regimes are changing and pH is
      decreasing. These unparalleled changes present new challenges for managing our
      seas, as we are only just beginning to understand the ecological manifestations
      of these climate alterations. The Marine Strategy Framework Directive requires
      all European Member States to achieve good environmental status (GES) in their
      seas by 2020; this means management towards GES will take place against a
      background of climate-driven macroecological change. Each Member State must set
      environmental targets to achieve GES; however, in order to do so, an
      understanding of large-scale ecological change in the marine ecosystem is
      necessary. Much of our knowledge of macroecological change in the North Atlantic
      is a result of research using data gathered by the Continuous Plankton Recorder
      (CPR) survey, a near-surface plankton monitoring programme that has been sampling
      in the North Atlantic since 1931. CPR data indicate that North Atlantic and North
      Sea plankton dynamics are responding to both climate and human-induced changes,
      presenting challenges to the development of pelagic targets for achievement of
      GES in European Seas. Thus, the continuation of long-term ecological time series
      such as the CPR survey is crucial for informing and supporting the sustainable
      management of European seas through policy mechanisms.

PMID- 23129716
TI  - Oceanographers' contribution to climate modelling and prediction: progress to
      date and a future perspective.
AB  - The ocean plays an essential role in determining aspects of the climate through
      its influence on coupled processes involving the atmosphere, cyrosphere and
      biogeochemistry, including budgets of heat and carbon dioxide and sea-level rise.
      Here, the key developments in ocean modelling over the past 20 years are reviewed
      and the prospects for the next 20 years are outlined, considering a hierarchy of
      idealized, conceptual and realistic modelling frameworks. It is emphasized that
      any long-term modelling strategy needs to be underpinned and complemented by
      fundamental theoretical and observational research activities. The need to be
      aware of the societal and technological drivers that will shape future research
      directions is also articulated.

PMID- 23129717
TI  - Oceans of opportunity or rough seas? What does the future hold for developments
      in European marine policy?
AB  - The management of European seas is undergoing a process of major reform. In the
      past, oceans and coastal policy has traditionally evolved in a fragmented and
      uncoordinated manner, developed by different sector-based agencies and arms of
      government with competing aims and objectives. Recently, the call for integrated
      and ecosystem-based approaches has driven the conceptualization of a new
      approach. At the scale of Europe through the Integrated Maritime Policy and
      Marine Strategy Framework Directive and in national jurisdictions such as the
      Marine and Coastal Access Act in the United Kingdom, ecosystem-based planning is
      becoming the norm. There are major challenges to this process and this paper
      explores, in particular, the opportunities inherent in building truly integrated
      approaches that cross different sectors of activity, integrate across scales,
      incorporate public involvement and build a sense of oceans citizenship.

PMID- 23129718
TI  - Modified thoraco-mediastinal plication (Andrews thoracoplasty) for post
      pneumonectomy empyema: experience with 30 consecutive cases.
AB  - OBJECTIVES: The aim of our study is to evaluate the results of thoraco
      mediastinal plication for the treatment of post-pneumonectomy empyema. METHODS:
      From 1 January 1985 to 1 January 2011, 30 patients underwent post-pneumonectomy
      empyema through a modified thoraco-mediastinal plication procedure (Andrews
      thoracoplasty). Indications for pneumonectomy included cancer (25 cases),
      tuberculosis (3 cases), and bronchiectasis (two cases). Rib resection was
      performed according to the topography of the cavity, ranging between 5 and 10.
      Neighbourhood muscle flaps were used in 22 cases but extensive mobilization was
      performed only in our last 4 cases, the aim of the procedure being the complete
      obliteration of the infected space. Bronchial fistula was present in 14 cases and
      was closed and reinforced with the use of flaps (intercostal 12 cases, serratus 1
      case, and omentum 1 case). RESULTS: Overall mortality was 6.7% (2 cases); 2
      patients (6.7%) presented with recurrence of the empyema requiring an open-window
      procedure and another patient (3.3%) presented with local tumoral recurrence.
      Intensive care unit hospitalization ranged between 1 and 14 days, with a median
      of 4 days, while overall postoperative hospitalization ranged between 23 and 52
      days with a median of 32 days, the patients being discharged with healed wounds.
      Kaplan-Meier analysis of the oncologic patients showed a median survival of 41
      months from thoraco-mediastinal plication. The presence of bronchial fistula had
      no statistically significant impact on the immediate outcome (mortality, need for
      postoperative prolonged mechanical ventilation, intensive care and overall
      postoperative hospitalization, P > 0.05 for all the parameters). CONCLUSIONS:
      Space-filling procedures are a valuable option for treating post-pneumonectomy
      empyema. The major advantages are the complete obliteration of the infected space
      and the quick healing from a single procedure; the major disadvantages are the
      magnitude of the procedure (with associated mortality and morbidity) and the
      permanent chest mutilation. Several technical details may improve the results and
      reduce the chest wall mutilation.

PMID- 23129719
TI  - Decomposing the association between the amount of exposure and the frequency of
      self-reported involvement in a road crash.
AB  - We tried to obtain preliminary evidence to test the hypothesis that the
      association between driving exposure and the frequency of reporting a road crash
      can be decomposed into two paths: direct and indirect (mediated by risky driving
      patterns). In a cross-sectional study carried out between 2007 and 2010, a sample
      of 1114 car drivers who were students at the University of Granada completed a
      questionnaire with items about driving exposure during the previous year, risk
      related driving circumstances and involvement in road crashes. We applied the
      decomposition procedure proposed by Buis for logit models. The indirect path
      showed a strong dose-response relationship with the frequency of reporting a road
      crash, whereas the direct path did not. The decomposition procedure was able to
      identify the indirect path as the main explanatory mechanism for the association
      between exposure and the frequency of reporting a road crash. 

PMID- 23129720
TI  - Trends and inequalities in cardiovascular disease mortality across 7932 English
      electoral wards, 1982-2006: Bayesian spatial analysis.
AB  - BACKGROUND: Cardiovascular disease (CVD) mortality has more than halved in
      England since the 1980s, but there are few data on small-area trends. We
      estimated CVD mortality by ward in 5-year intervals between 1982 and 2006, and
      examined trends in relation to starting mortality, region and community
      deprivation. METHODS: We analysed CVD death rates using a Bayesian spatial
      technique for all 7932 English electoral wards in consecutive 5-year intervals
      between 1982 and 2006, separately for men and women aged 30-64 years and >=65
      years. RESULTS: Age-standardized CVD mortality declined in the majority of wards,
      but increased in 186 wards for women aged >=65 years. The decline was larger
      where starting mortality had been higher. When grouped by deprivation quintile,
      absolute inequality between most- and least-deprived wards narrowed over time in
      those aged 30-64 years, but increased in older adults; relative inequalities
      worsened in all four age-sex groups. Wards with high CVD mortality in 2002-06
      fell into two groups: those in and around large metropolitan cities in northern
      England that started with high mortality in 1982-86 and could not 'catch up',
      despite impressive declines, and those that started with average or low mortality
      in the 1980s but 'fell behind' because of small mortality reductions.
      CONCLUSIONS: Improving population health and reducing health inequalities should
      be treated as related policy and measurement goals. Ongoing analysis of mortality
      by small area is essential to monitor local effects on health and health
      inequalities of the public health and healthcare systems.

PMID- 23129721
TI  - Between-assay variability of faecal calprotectin enzyme-linked immunosorbent
      assay kits.
AB  - BACKGROUND: Faecal calprotectin (f-Cp), a marker of intestinal inflammation, can
      be used to distinguish between functional and organic bowel disease. F-Cp,
      following extraction, is commonly quantified using enzyme-linked immunosorbent
      assays (ELISAs) but there are no data comparing the different f-Cp assays or
      sample extraction devices. We, therefore, evaluated and compared the performance
      of the Immunodiagnostik, Buhlmann and Eurospital f-Cp ELISA assays as well as the
      Roche, Immunodiagnostik and ScheBo Biotech commercial faecal extraction devices.
      We also briefly report results from a pilot f-Cp external quality assurance (EQA)
      scheme. METHODS: Imprecision, linearity, recovery, drift and limit of
      quantitation of the f-Cp assays were evaluated and between-assay variability
      assessed. The three commercial sample extraction devices were compared with the
      manual weighing method. Four faecal samples were distributed as part of a pilot
      EQA scheme to 15 laboratories using quantitative ELISA f-Cp assays. RESULTS: The
      three f-Cp assays demonstrated adequate intra-/interbatch imprecision, linearity
      and recovery. The cross-comparison study and EQA data demonstrated that, for the
      same sample, the Buhlmann assay reports up to 3.8 times higher f-Cp
      concentrations than the Immunodiagnostik and Eurospital assays. On average, the
      commercial extraction devices led to a 7.8-28.1% under-recovery of f-Cp in
      comparison to the manual weighing method. CONCLUSIONS: Laboratories should be
      aware of the lack of the assay standardization, as demonstrated by the between
      assay variability. A comparison between f-Cp concentrations reported by these
      assays and clinical markers of disease severity is required in order to determine
      their diagnostic accuracy. The EQA scheme represents the first available
      programme for f-Cp.

PMID- 23129722
TI  - Identification of a rare variant haemoglobin (Hb Sinai-Baltimore) causing
      spuriously low haemoglobin A(1c) values on ion exchange chromatography.
AB  - Commonly used methods for assay of haemoglobin A(1c) (HbA(1c)) are susceptible to
      interference from the presence of haemoglobin variants. In many systems, the
      common variants can be identified but scientists and pathologists must remain
      vigilant for more subtle variants that may result in spuriously high or low
      HbA(1c) values. It is clearly important to recognize these events whether HbA(1c)
      is being used as a monitoring tool or, as is increasingly the case, for
      diagnostic purposes. We report a patient with a rare haemoglobin variant (Hb
      Sinai-Baltimore) that resulted in spuriously low values of HbA(1c) when assayed
      using ion exchange chromatography, and the steps taken to elucidate the nature of
      the variant.

PMID- 23129723
TI  - Interference of ethylene glycol with (L)-lactate measurement is assay-dependent.
AB  - BACKGROUND: Metabolites of ethylene glycol (EG) can cross-react in l-lactate
      assays, leading to falsely elevated serum lactate levels in case of EG
      intoxication. In this study, we evaluated the effects of EG and its metabolites
      on routinely used lactate measuring methods. METHODS: Serum aliquots were spiked
      with either l-lactate, EG or one of its metabolites (all 12.5 mmol/L): glyoxal,
      glycolate, glyoxylic acid or oxalate. An unspiked sample (l-lactate 2.6 mmol/L)
      served as a control. l-Lactate levels in these samples were measured in 31
      national hospitals on 20 different analysers from nine manufacturers. RESULTS:
      The l-lactate concentrations in the control sample and in the samples spiked with
      l-lactate, EG, glyoxal and oxalate provided correct results by all routinely used
      methods. However, the glycolate and glyoxylic acid spiked samples resulted in
      falsely elevated l-lactate concentration with all blood gas methods and with the
      majority of general chemistry methods using l-lactate oxidase. CONCLUSION: The EG
      metabolites glycolate and glyoxylic acid were shown to falsely elevate l-lactate
      results with most of the currently used methods due to cross-reactivity with the
      oxidase enzyme. Falsely elevated l-lactate results can lead to misdiagnosis and
      inappropriate management of patients with EG intoxication.

PMID- 23129724
TI  - The relative effects of fat versus muscle mass on cystatin C and estimates of
      renal function in healthy young men.
AB  - BACKGROUND: It is well known that plasma creatinine concentration is affected by
      muscle mass, while some studies have suggested cystatin C is affected by body
      mass index (BMI). Our aim was to assess the effects of lean versus fat mass on
      cystatin C and creatinine derivative equations in estimating glomerular
      filtration rate (GFR) in healthy young men. METHODS: Three groups of participants
      were studied: those classified as normal (BMI 18-25 kg/m(2) with body fat <30%);
      muscular subjects (BMI >30 kg/m(2) and body fat <20%); and obese subjects (BMI
      >30 kg/m(2) and body fat >30%). All underwent diethylenetriamine pentaacetic acid
      GFR, bio-electrical impedance and dual-energy X-ray absorptiometry body
      composition analysis, measurement of plasma cystatin C, creatinine and high
      sensitivity C-reactive protein and completed a diet record. RESULTS: Cystatin C
      was highest in the obese group (0.77 mg/L; 95% confidence intervals [CI] 0.69
      0.77) and creatinine was highest in the muscular group (90.1 MUmol/L; 95% CI 84.3
      96.0). On multivariate analysis, body fat and GFR (P = 0.003) were significant
      determinants of cystatin C; muscle mass and age affected creatinine significantly
      (P = 0.02). Using cystatin C equations, Le Bricon and Hoek showed significantly
      lower estimated GFR in the obese group but performed reasonably well within 50%,
      30% and 20% of GFR. Creatinine equations showed significant underestimations of
      GFR for the muscular group. CONCLUSIONS: Body fat is a significant determinant of
      cystatin C while creatinine concentration is highly affected by muscle mass and
      age. Body composition plays an important role in the interpretation of renal
      function. Cystatin C equations are still accurate in predicting GFR in our
      healthy male group without chronic kidney disease.

PMID- 23129725
TI  - Sodium fluoride: an ineffective inhibitor of glycolysis.
AB  - Entrenched in current laboratory protocols for the measurement of plasma glucose
      is the false belief that sodium fluoride (NaF) is an effective inhibitor of
      glycolysis. The failure of NaF to properly control glycolysis decreases plasma
      glucose concentrations. The amount of the decrease can be clinically significant.
      The most recent (2011) laboratory guidelines for diagnosis and management of
      diabetes mellitus, approved by the American Diabetes Association, no longer
      recommend the use of NaF alone to control glycolysis. If plasma cannot be iced
      and separated from cells within 30 min of collection, the new guidelines
      recommend the use of a tube that contains a low pH buffer such as citrate. Proper
      control of glycolysis will affect current glucose cut-off points, but the exact
      effect is yet to be defined.

PMID- 23129726
TI  - Inflammatory bowel disease in central India: a single centre experience over five
      years.
AB  - In this retrospective study, the records of all patients diagnosed with
      inflammatory bowel disease between 2005 and 2010 were analysed. Ulcerative
      colitis is far more common than Crohn's disease in our setting. The incidence is
      similar in both sexes and the age at diagnosis for both is similar. Limited left
      sided ulcerative colitis is more common. Crohn's disease is difficult to diagnose
      and is commonly treated as tuberculosis in our setting.

PMID- 23129727
TI  - When is an outbreak not an outbreak? Fit, divergent strains of Mycobacterium
      tuberculosis display independent evolution of drug resistance in a large London
      outbreak.
AB  - OBJECTIVES: To study the evolutionary relationship of Mycobacterium tuberculosis
      isolates from 13 patients in a large outbreak of isoniazid-resistant tuberculosis
      in London. METHODS: Genotypic and phenotypic susceptibility tests were performed.
      Molecular genotyping using restriction fragment length polymorphisms and
      mycobacterial interspersed repetitive units was carried out. Additionally, the
      generation times of 13 strains of M. tuberculosis from the outbreak were measured
      to determine relative fitness. RESULTS: Genotypic and phenotypic susceptibility
      testing demonstrated variations between isolates. Polymorphisms causing isoniazid
      resistance varied within clusters of isolates that were indistinguishable by
      standard genotyping. The measurement of in vitro generation times demonstrated
      that the fitness of the resistant strains was not significantly different from
      either wild-type or susceptible isolates in the outbreak, indicating that
      apparently no fitness cost was associated with the acquisition of drug
      resistance. CONCLUSIONS: It appears that this outbreak comprised a heterogeneous
      collection of closely related strains, which appear to exhibit more variation
      than would usually be associated with a point source outbreak. These strains
      appear to have evolved by acquisition of additional antimicrobial resistance
      mutations while remaining competitive. The acquired resistance and retained
      competitiveness may be partly responsible for the difficulty in controlling the
      outbreak.

PMID- 23129728
TI  - Voluntary ban on cephalosporin use in Danish pig production has effectively
      reduced extended-spectrum cephalosporinase-producing Escherichia coli in
      slaughter pigs.
AB  - OBJECTIVES: To measure the effect of a voluntary ban on cephalosporin usage in
      the Danish pig production on the prevalence of extended-spectrum cephalosporinase
      (ESC)-producing Escherichia coli in pigs and pork. METHODS: Data on cephalosporin
      consumption were obtained from the VetStat database. For detection of ESC
      producing E. coli, three sampling types were included: at slaughter, caecal
      samples were collected from pigs in 2009 and 2010 (June) before and in two
      periods (2010 and 2011) after a voluntary ban on cephalosporins was effected
      (July 2010); at farm level, pools of five stool samples from different pigsties
      were collected in 2010 and in 2011; and samples from pork were collected randomly
      at retail stores and outlets from 2009 to 2011. ESC-producing E. coli was
      isolated after selective enrichment in MacConkey broth with 1 mg/L ceftriaxone.
      ESC genes were detected using PCR, microtube array and sequencing. RESULTS: From
      July 2010 the consumption of cephalosporins approximated zero. The occurrence of
      ESC-producing E. coli in pigs at slaughter was not significantly different
      (P=0.7) between 2009 [10.8% (85/786)] and 2010 [11.8% (48/407)], but in 2011 the
      occurrence [3.6% (28/777)] decreased significantly (P<0.001). A significant
      decrease (P=0.002) in occurrence of ESC-producing E. coli at pig farm level from
      2010 [11% (11/99)] to 2011 (0/78) was also observed. The bla(CTX-M-1) gene was
      most often detected (63%), but bla(CTX-M-14) and bla(CTX-M-15) were also found.
      Occurrence in pork was between 1.3% and 0.9%. CONCLUSIONS: The discontinuation of
      an already low use of cephalosporins in pig production has significantly reduced
      the occurrence of ESC-producing E. coli.

PMID- 23129729
TI  - Efficacy and pharmacodynamics of voriconazole combined with anidulafungin in
      azole-resistant invasive aspergillosis.
AB  - OBJECTIVES: Azole resistance is an emerging problem in the treatment of
      Aspergillus fumigatus infections. Combination therapy may be an alternative
      approach to improve therapeutic outcome in azole-resistant invasive aspergillosis
      (IA). The in vivo efficacy of voriconazole and anidulafungin was investigated in
      a non-neutropenic murine model of IA using voriconazole-susceptible and
      voriconazole-resistant A. fumigatus clinical isolates. METHODS: Treatment groups
      consisted of voriconazole monotherapy, anidulafungin monotherapy and voriconazole
      + anidulafungin at 2.5, 5, 10 and 20 mg/kg body weight/day for 7 consecutive
      days. In vitro and in vivo drug interactions were analysed by non-parametric
      Bliss independence and non-linear regression analysis. RESULTS: Synergistic
      interaction between voriconazole and anidulafungin against the voriconazole
      susceptible isolate (AZN 8196) was observed in vitro and in vivo. However, among
      animals infected with the voriconazole-resistant isolate (V 52-35), 100% survival
      was observed only in groups receiving the highest doses (20 mg/kg voriconazole +
      20 mg/kg anidulafungin). For this isolate, additivity, but not synergy, was
      observed in vivo. CONCLUSIONS: Combination of voriconazole and anidulafungin was
      synergistic in voriconazole-susceptible IA, but additive in voriconazole
      resistant IA. There is a clear benefit of combining voriconazole and
      anidulafungin, but the reduced effect of combination therapy in azole-resistant
      IA raises some concern.

PMID- 23129730
TI  - Improving existing tools for Mycobacterium xenopi treatment: assessment of drug
      combinations and characterization of mouse models of infection and chemotherapy.
AB  - BACKGROUND: Mycobacterium xenopi is a common agent of non-tuberculous
      mycobacterial lung diseases in Europe. However, an optimal treatment regimen for
      M. xenopi infection has not yet been established. Appropriate in vitro and in
      vivo model systems are needed for characterization of the activity of potential
      drugs and drug combinations against M. xenopi. METHODS: We utilized three
      experimental platforms to analyse the anti-M. xenopi activity of single and
      combination drug regimens. First, we determined the bacteriostatic and
      bactericidal activities of drugs alone and in combination in vitro. Second, we
      used serum from treated mice to evaluate drug activities ex vivo. Third, we
      analysed M. xenopi growth in four strains of mice (BALB/c, C57BL/6, beige and
      athymic nude) and developed a mouse model of chemotherapy for this infection.
      RESULTS: Two-drug combinations of ethambutol with rifampicin, rifapentine or
      moxifloxacin, and of clarithromycin with moxifloxacin were bactericidal in vitro,
      and the combination of ethambutol and rifampicin with either clarithromycin or
      moxifloxacin showed significant bactericidal activity ex vivo. Nude mice were the
      most susceptible strain to M. xenopi infection, and in this model amikacin
      containing regimens were the most effective against M. xenopi. No difference in
      activity was found between regimens containing clarithromycin and moxifloxacin in
      vivo. CONCLUSION: The ethambutol/rifampicin combination with clarithromycin or
      moxifloxacin had significant bactericidal activity against M. xenopi. The nude
      mouse, being highly susceptible to M. xenopi, can be utilized for in vivo
      chemotherapy studies for this infection.

PMID- 23129731
TI  - Urine drug testing of chronic pain patients. V. Prevalence of propoxyphene
      following its withdrawal from the United States market.
AB  - Propoxyphene is an opioid analgesic that was surrounded by controversy concerning
      its safety and efficacy during its lifespan in the US market. Propoxyphene was
      withdrawn in November of 2010 from the US market and is still being detected one
      year post-withdrawal in urine specimens from the pain management population. In
      this study, the prevalence of propoxyphene was determined in a total of 417,914
      urine specimens collected from 630 clinics involved in pain management located in
      24 states during the period of January 1, 2010, through December 31, 2011.
      Propoxyphene and norpropoxyphene were measured in urine by a validated liquid
      chromatography-tandem mass spectrometry procedure with a lower limit of
      quantitation of 50 ng/mL. The positivity rate for propoxyphene prevalence
      declined sharply between November and December of 2010 and further declined at a
      gradual rate, ending in a prevalence of 0.27% (one out of every 370 specimens, n
      = 25,658) for the month of December 2011. The presented data provide evidence of
      the dramatic decline in the use of propoxyphene products since their removal from
      the medical market, and may be beneficial to US urine drug testing programs
      determining the need for continual monitoring of propoxyphene levels.

PMID- 23129732
TI  - Epicardial fat thickness in heart failure and other clinical conditions.

PMID- 23129734
TI  - Endovascular treatment of critical ischemia in the diabetic foot: new thresholds,
      new anatomies.
AB  - This review discusses the role of endovascular treatment in diabetic patients
      with critical limb ischemia (CLI). Angioplasty of the femoropopliteal region
      achieves similar technical success and limb salvage rates in diabetic and
      nondiabetic patients. Angioplasty in as many as possible tibial vessels is
      accompanied by more complete and faster ulcer healing as well as better limb
      salvage rates compared to isolated tibial angioplasty. Targeted revascularization
      of a specific vessel responsible for the perfusion of a specific ulcerated area
      is a promising new approach: it replaces revascularization of the
      angiographically easiest-to-access tibial vessel, even if this is not directly
      responsible for the perfusion of the ulcerated area, by revascularization of area
      specific vascular territories. In conclusion, the endovascular approach shows
      very high efficacy in ulcer healing for diabetic patients with CLI. Larger
      prospective studies are now needed to estimate the long-term results of this
      approach. 

PMID- 23129733
TI  - Therapeutic angiogenesis in critical limb ischemia.
AB  - Critical limb ischemia (CLI) is a severe form of peripheral artery disease
      associated with high morbidity and mortality. The primary therapeutic goals in
      treating CLI are to reduce the risk of adverse cardiovascular events, relieve
      ischemic pain, heal ulcers, prevent major amputation, and improve quality of life
      (QoL) and survival. These goals may be achieved by medical therapy, endovascular
      intervention, open surgery, or amputation and require a multidisciplinary
      approach including pain management, wound care, risk factors reduction, and
      treatment of comorbidities. No-option patients are potential candidates for the
      novel angiogenic therapies. The application of genetic, molecular, and cellular
      based modalities, the so-called therapeutic angiogenesis, in the treatment of
      arterial obstructive diseases has not shown consistent efficacy. This article
      summarizes the current status related to the management of patients with CLI and
      discusses the current findings of the emerging modalities for therapeutic
      angiogenesis.

PMID- 23129735
TI  - Mast cell sarcoma: a rare and aggressive entity--report of two cases and review
      of the literature.

PMID- 23129736
TI  - Use of research biopsies in clinical trials: are risks and benefits adequately
      discussed?
AB  - PURPOSE: Although the incorporation of research biopsies into clinical trials is
      increasing, limited information is available about how study protocols and
      informed consents integrate and describe their use. METHODS: All therapeutic
      clinical trials in which image-guided research biopsies were performed from
      January 1, 2005, to October 1, 2010, were identified from an interventional
      radiology database. Data from study protocols and informed consents were
      extracted and analyzed. Procedural complications were recorded. RESULTS: A total
      of 57 clinical trials were identified, of which 38 (67%) contained at least one
      mandatory biopsy. The analysis of the research biopsy tumor tissue was a study
      end point in 95% of trials. The primary indication for a research biopsy was for
      integral biomarker analysis in 32% and for correlative science in 68% of trials.
      A statistical analytic plan for the correlative science research biopsy tumor
      tissue was mentioned in 26%, described as exploratory in 51%, and not mentioned
      in 23% of trials. For studies with mandatory biopsies, biopsy was an eligibility
      criterion in 71% of trials, and a statistical justification for the research
      biopsy sample size was present in 50% of trials. A total of 745 research biopsies
      were performed on 576 patients. Overall and major complication rates were 5.2%
      (39 of 745 biopsies) and 0.8% (six of 745 biopsies), respectively. Complication
      rates for intrathoracic and abdominal/pelvic solid organ biopsies were 17.1% (36
      of 211 biopsies) and 1.6% (three of 189 biopsies), respectively. Site-stratified
      research biopsy-related risks were discussed in five consents. CONCLUSION: A
      better representation of the risks and benefits of research biopsies in study
      protocols and informed consents is needed.

PMID- 23129737
TI  - Gonadotropin-releasing hormone agonist for the prevention of chemotherapy-induced
      ovarian failure in patients with lymphoma: 1-year follow-up of a prospective
      randomized trial.
AB  - PURPOSE: To assess the efficacy of gonadotropin-releasing hormone agonist (GnRHa)
      in preventing chemotherapy-induced ovarian failure in patients treated for
      Hodgkin or non-Hodgkin lymphoma within the setting of a multicenter, randomized,
      prospective trial. PATIENTS AND METHODS: Patients age 18 to 45 years were
      randomly assigned to receive either the GnRHa triptorelin plus norethisterone
      (GnRHa group) or norethisterone alone (control group) concomitantly with
      alkylating agents containing chemotherapy. The primary end point was the
      premature ovarian failure (POF) rate (follicle-stimulating hormone [FSH] >= 40
      IU/L) after 1 year of follow-up. RESULTS: Eighty-four of 129 randomly assigned
      patients completed the 1-year follow-up. The mean FSH values were higher in the
      control group than in the GnRHa group during chemotherapy; however, this
      difference was no longer observed after 6 months of follow-up. After 1 year, 20%
      and 19% of patients in the GnRHa and control groups, respectively, exhibited POF
      (P = 1.00). More than half of patients in each group completely restored their
      ovarian function (FSH < 10 IU/L), but the anti-Mullerian hormone values were
      higher in the GnRHa group than in the control group (1.4 +/- 0.35 v 0.5 +/- 0.15
      ng/mL, respectively; P = .040). The occurrence of adverse events was similar in
      both groups with the exception of metrorrhagia, which was more frequently
      observed in the control group than the GnRHa group (38.4% v 15.6%, respectively;
      P = .024). CONCLUSION: Approximately 20% of patients in both groups exhibited POF
      after 1 year of follow-up. Triptorelin was not associated with a significant
      decreased risk of POF in young patients treated for lymphoma but may provide
      protection of the ovarian reserve.

PMID- 23129739
TI  - Toward improved understanding of the ethical and clinical issues surrounding
      mandatory research biopsies.

PMID- 23129738
TI  - Bortezomib added to daunorubicin and cytarabine during induction therapy and to
      intermediate-dose cytarabine for consolidation in patients with previously
      untreated acute myeloid leukemia age 60 to 75 years: CALGB (Alliance) study
      10502.
AB  - PURPOSE: The purpose of this study was to determine remission induction frequency
      when bortezomib was combined with daunorubicin and cytarabine in previously
      untreated older adults with acute myeloid leukemia (AML) and safety of bortezomib
      in combination with consolidation chemotherapy consisting of intermediate-dose
      cytarabine (Int-DAC). PATIENTS AND METHODS: Ninety-five adults (age 60 to 75
      years; median, 67 years) with previously untreated AML (including therapy-related
      and previous myelodysplastic syndrome) received bortezomib 1.3 mg/m(2)
      intravenously (IV) on days 1, 4, 8, and 11 with daunorubicin 60 mg/m(2) on days 1
      through 3 and cytarabine 100 mg/m(2) by continuous IV infusion on days 1 through
      7. Patients who achieved complete remission (CR) received up to two courses of
      consolidation chemotherapy with cytarabine 2 gm/m(2) on days 1 through 5 with
      bortezomib. Three cohorts with escalating dose levels of bortezomib were tested
      (0.7, 1.0, and 1.3 mg/m(2)). Dose-limiting toxicities were assessed during the
      first cycle of consolidation. The relationship between cell surface expression of
      CD74 and clinical outcome was assessed. RESULTS: Frequency of CR was 65% (62 of
      95), and 4% of patients (four of 95) achieved CR with incomplete platelet
      recovery (CRp). Eleven patients developed grade 3 sensory neuropathy. Bortezomib
      plus Int-DAC proved tolerable at the highest dose tested. Lower CD74 expression
      was associated with CR/CRp (P = .04) but not with disease-free or overall
      survival. CONCLUSION: The addition of bortezomib to standard 3 + 7 daunorubicin
      and cytarabine induction chemotherapy for AML resulted in an encouraging
      remission rate. The maximum tested dose of bortezomib administered in combination
      with Int-DAC for remission consolidation was 1.3 mg/m(2) and proved tolerable.
      Further testing of this regimen is planned.

PMID- 23129740
TI  - Possible role for tocilizumab, an anti-interleukin-6 receptor antibody, in
      treating cancer cachexia.

PMID- 23129741
TI  - Breast cancer follow-up and management after primary treatment: American Society
      of Clinical Oncology clinical practice guideline update.
AB  - PURPOSE: To provide recommendations on the follow-up and management of patients
      with breast cancer who have completed primary therapy with curative intent.
      METHODS: To update the 2006 guideline of the American Society of Clinical
      Oncology (ASCO), a systematic review of the literature published from March 2006
      through March 2012 was completed using MEDLINE and the Cochrane Collaboration
      Library. An Update Committee reviewed the evidence to determine whether the
      recommendations were in need of updating. RESULTS: There were 14 new publications
      that met inclusion criteria: nine systematic reviews (three included meta
      analyses) and five randomized controlled trials. After its review and analysis of
      the evidence, the Update Committee concluded that no revisions to the existing
      ASCO recommendations were warranted. RECOMMENDATIONS: Regular history, physical
      examination, and mammography are recommended for breast cancer follow-up.
      Physical examinations should be performed every 3 to 6 months for the first 3
      years, every 6 to 12 months for years 4 and 5, and annually thereafter. For women
      who have undergone breast-conserving surgery, a post-treatment mammogram should
      be obtained 1 year after the initial mammogram and at least 6 months after
      completion of radiation therapy. Thereafter, unless otherwise indicated, a yearly
      mammographic evaluation should be performed. The use of complete blood counts,
      chemistry panels, bone scans, chest radiographs, liver ultrasounds, pelvic
      ultrasounds, computed tomography scans, [(18)F]fluorodeoxyglucose-positron
      emission tomography scans, magnetic resonance imaging, and/or tumor markers
      (carcinoembryonic antigen, CA 15-3, and CA 27.29) is not recommended for routine
      follow-up in an otherwise asymptomatic patient with no specific findings on
      clinical examination.

PMID- 23129743
TI  - What is better for older patients with acute myeloid leukemia?

PMID- 23129742
TI  - Randomized phase III trial of induction chemotherapy with docetaxel, cisplatin,
      and fluorouracil followed by surgery versus up-front surgery in locally advanced
      resectable oral squamous cell carcinoma.
AB  - PURPOSE: To evaluate induction chemotherapy with docetaxel, cisplatin, and
      fluorouracil (TPF) followed by surgery and postoperative radiotherapy versus up
      front surgery and postoperative radiotherapy in patients with locally advanced
      resectable oral squamous cell carcinoma (OSCC). PATIENTS AND METHODS: A
      prospective open-label phase III trial was conducted. Eligibility criteria
      included untreated stage III or IVA locally advanced resectable OSCC. Patients
      received two cycles of TPF induction chemotherapy (docetaxel 75 mg/m(2) on day 1,
      cisplatin 75 mg/m(2) on day 1, and fluorouracil 750 mg/m(2) on days 1 to 5)
      followed by radical surgery and postoperative radiotherapy (54 to 66 Gy) versus
      up-front radical surgery and postoperative radiotherapy. The primary end point
      was overall survival (OS). Secondary end points included local control and
      safety. RESULTS: Of the 256 patients enrolled onto this trial, 222 completed the
      full treatment protocol. There were no unexpected toxicities, and induction
      chemotherapy did not increase perioperative morbidity. The clinical response rate
      to induction chemotherapy was 80.6%. After a median follow-up of 30 months, there
      was no significant difference in OS (hazard ratio [HR], 0.977; 95% CI, 0.634 to
      1.507; P = .918) or disease-free survival (HR, 0.974; 95% CI, 0.654 to 1.45; P =
      .897) between patients treated with and without TPF induction. Patients in the
      induction chemotherapy arm with a clinical response or favorable pathologic
      response (<= 10% viable tumor cells) had superior OS and locoregional and distant
      control. CONCLUSION: Our study failed to demonstrate that TPF induction
      chemotherapy improves survival compared with up-front surgery in patients with
      resectable stage III or IVA OSCC.

PMID- 23129744
TI  - Low hepatitis C viral load predicts better long-term outcomes in patients
      undergoing resection of hepatocellular carcinoma irrespective of serologic
      eradication of hepatitis C virus.
AB  - PURPOSE: Hepatitis C virus (HCV) infection has been recognized as a potent risk
      factor for the postoperative recurrence of hepatocellular carcinoma (HCC).
      However, little is known about the impact of HCV viral load on surgical outcomes.
      The study objective was to investigate clinical significance of HCV viral load on
      long-term outcomes of HCC. PATIENTS AND METHODS: Three hundred seventy patients
      who were classified as Child-Pugh class A and underwent curative liver resections
      for HCV-related HCC were divided into low and high viral load groups (<= or > 5.3
      log(10)IU/mL) based on the results of a minimum P value approach to predict
      moderate to severe activity of hepatitis; the clinical outcomes were then
      compared. RESULTS: The 5-year recurrence-free survival rate was 36.1% in the low
      viral load group and 12.4% in the high viral load group (P < .001). The 5-year
      overall survival rate was 76.6% in the low viral load group and 57.7% in the high
      viral load group (P < .001). Multivariate analysis confirmed significant
      correlation between high viral load and tumor recurrence with a hazard ratio of
      1.87 (95% CI, 1.41 to 2.48; P < .001). Subanalysis revealed that the favorable
      results in the low viral load group were not attributed to whether or not
      serologic eradication of HCV was obtained both in primary and recurrent lesions.
      CONCLUSION: Low HCV viral load predicts better long-term surgical outcomes in
      patients with HCC regardless of the serologic eradication of HCV.

PMID- 23129745
TI  - When azanucleoside treatment can be curative: nonintensive bridging strategy
      before allografting in older patients with myelodysplastic syndrome/acute myeloid
      leukemia.

PMID- 23129746
TI  - Randomized trial of myeloablative conditioning regimens: busulfan plus
      cyclophosphamide versus busulfan plus fludarabine.
AB  - PURPOSE: We conducted a phase III randomized clinical trial to compare two
      myeloablative conditioning regimens for allogeneic hematopoietic cell
      transplantation (HCT) in patients with leukemia and myelodysplastic syndrome.
      PATIENTS AND METHODS: After randomization, 64 patients received busulfan (3.2
      mg/kg per day * 4 days) plus cyclophosphamide (60 mg/kg per day * 2 days; BuCy),
      and 62 patients received busulfan (same dose and schedule) plus fludarabine (30
      mg/m(2) per day * 5 days; BuFlu). RESULTS: The median age was 41 years (range, 17
      to 59 years). Five patients in the BuFlu arm experienced graft failure (primary,
      n = 1; secondary, n = 4). At 4 weeks after HCT, the median percentage of
      recipient hematopoietic chimerism was significantly greater in the BuFlu arm (0%
      v 5.5%; P < .001), and complete donor chimerism was greater in the BuCy arm
      (97.2% v 44.4%; P < .001). Severe (grade 3 or higher) infection and
      gastrointestinal adverse events were significantly more common in the BuCy arm,
      but the frequencies of hepatic adverse events were similar in the two arms.
      Nonrelapse mortality was similar in the two arms, but the BuCy arm had better
      overall survival (OS), relapse-free survival (RFS), and event-free survival (EFS;
      OS at 2 years, 67.4% v 41.4%, P = .014; RFS, 74.7% v 54.9%, P = .027; EFS, 60.7%
      v 36.0%, P = .014). CONCLUSION: Our results indicate that the BuFlu regimen is
      not a suitable replacement for the BuCy regimen in young adults who are eligible
      for myeloablative conditioning therapy for allogeneic HCT.

PMID- 23129747
TI  - Transcriptional regulator early growth response gene 2 (Egr2) is required for T
      cell anergy in vitro and in vivo.
AB  - T cell receptor engagement in the absence of costimulation results in a
      hyporesponsive state termed anergy. Understanding the transcriptional regulation
      of other T cell differentiation states has provided critical information
      regarding the biology of T cell regulation in vivo. However, the transcriptional
      regulation of T cell anergy has been poorly understood. Using the key anergy
      target gene diacylglycerol kinase (DGK) alpha as a focal point, we identified
      early growth response gene 2 (Egr2) as a central transcription factor that
      regulates the anergic state. Conditional Egr2 deletion in peripheral T cells
      abolishes induced expression of DGK-alpha and other anergy genes and restores
      Ras/MAPK signaling, IL-2 production, and proliferation upon attempted anergy
      induction. Using superantigen- and tumor-induced anergy models, we found that
      Egr2 is necessary for anergy induction in vivo. Collectively, our results
      implicate Egr2 as an essential transcriptional regulator of the T cell anergy
      program.

PMID- 23129748
TI  - Regulation of PTEN activity by p38delta-PKD1 signaling in neutrophils confers
      inflammatory responses in the lung.
AB  - Despite their role in resolving inflammatory insults, neutrophils trigger
      inflammation-induced acute lung injury (ALI), culminating in acute respiratory
      distress syndrome (ARDS), a frequent complication with high mortality in humans.
      Molecular mechanisms underlying recruitment of neutrophils to sites of
      inflammation remain poorly understood. Here, we show that p38 MAP kinase p38delta
      is required for recruitment of neutrophils into inflammatory sites. Global and
      myeloid-restricted deletion of p38delta in mice results in decreased alveolar
      neutrophil accumulation and attenuation of ALI. p38delta counteracts the activity
      of its downstream target protein kinase D1 (PKD1) in neutrophils and myeloid
      restricted inactivation of PKD1 leads to exacerbated lung inflammation.
      Importantly, p38delta and PKD1 conversely regulate PTEN activity in neutrophils,
      thereby controlling their extravasation and chemotaxis. PKD1 phosphorylates
      p85alpha to enhance its interaction with PTEN, leading to polarized PTEN
      activity, thereby regulating neutrophil migration. Thus, aberrant p38delta-PKD1
      signaling in neutrophils may underlie development of ALI and life-threatening
      ARDS in humans.

PMID- 23129749
TI  - Congenital B cell lymphocytosis explained by novel germline CARD11 mutations.
AB  - Nuclear factor-kappaB (NF-kappaB) controls genes involved in normal lymphocyte
      functions, but constitutive NF-kappaB activation is often associated with B cell
      malignancy. Using high-throughput whole transcriptome sequencing, we investigated
      a unique family with hereditary polyclonal B cell lymphocytosis. We found a novel
      germline heterozygous missense mutation (E127G) in affected patients in the gene
      encoding CARD11, a scaffolding protein required for antigen receptor (AgR)
      induced NF-kappaB activation in both B and T lymphocytes. We subsequently
      identified a second germline mutation (G116S) in an unrelated, phenotypically
      similar patient, confirming mutations in CARD11 drive disease. Like somatic, gain
      of-function CARD11 mutations described in B cell lymphoma, these germline CARD11
      mutants spontaneously aggregate and drive constitutive NF-kappaB activation.
      However, these CARD11 mutants rendered patient T cells less responsive to AgR
      induced activation. By reexamining this rare genetic disorder first reported four
      decades ago, our findings provide new insight into why activating CARD11
      mutations may induce B cell expansion and preferentially predispose to B cell
      malignancy without dramatically perturbing T cell homeostasis.

PMID- 23129750
TI  - Anti-apoE immunotherapy inhibits amyloid accumulation in a transgenic mouse model
      of Abeta amyloidosis.
AB  - The apolipoprotein E (APOE) epsilon4 allele is the strongest genetic risk factor
      for Alzheimer's disease (AD). The influence of apoE on amyloid beta (Abeta)
      accumulation may be the major mechanism by which apoE affects AD. ApoE interacts
      with Abeta and facilitates Abeta fibrillogenesis in vitro. In addition, apoE is
      one of the protein components in plaques. We hypothesized that certain anti-apoE
      antibodies, similar to certain anti-Abeta antibodies, may have antiamyloidogenic
      effects by binding to apoE in the plaques and activating microglia-mediated
      amyloid clearance. To test this hypothesis, we developed several monoclonal anti
      apoE antibodies. Among them, we administered HJ6.3 antibody intraperitoneally to
      4-mo-old male APPswe/PS1DeltaE9 mice weekly for 14 wk. HJ6.3 dramatically
      decreased amyloid deposition by 60-80% and significantly reduced insoluble
      Abeta40 and Abeta42 levels. Short-term treatment with HJ6.3 resulted in strong
      changes in microglial responses around Abeta plaques. Collectively, these results
      suggest that anti-apoE immunization may represent a novel AD therapeutic strategy
      and that other proteins involved in Abeta binding and aggregation might also be a
      target for immunotherapy. Our data also have important broader implications for
      other amyloidosis. Immunotherapy to proteins tightly associated with misfolded
      proteins might open up a new treatment option for many protein misfolding
      diseases.

PMID- 23129751
TI  - Procontractile G protein-mediated signaling pathways antagonistically regulate
      smooth muscle differentiation in vascular remodeling.
AB  - Vascular smooth muscle (Sm) cells (VSMCs) are highly plastic. Their
      differentiation state can be regulated by serum response factor (SRF), which
      activates genes involved in Sm differentiation and proliferation by recruiting
      cofactors, such as members of the myocardin family and ternary complex factors
      (TCFs), respectively. However, the extracellular cues and upstream signaling
      mechanisms regulating SRF-dependent VSMC differentiation under in vivo conditions
      are poorly understood. In this study, we show that the procontractile signaling
      pathways mediated by the G proteins G(12)/G(13) and G(q)/G(11) antagonistically
      regulate VSMC plasticity in different models of vascular remodeling. In mice
      lacking Galpha(12)/Galpha(13) or their effector, the RhoGEF protein LARG, RhoA
      dependent SRF-regulation was blocked and down-regulation of VSMC differentiation
      marker genes was enhanced. This was accompanied by an excessive vascular
      remodeling and exacerbation of atherosclerosis. In contrast, Sm-specific
      Galpha(q)/Galpha(11) deficiency blocked activation of extracellular signal
      regulated kinase 1/2 and the TCF Elk-1, resulting in a reduced VSMC
      dedifferentiation in response to flow cessation or vascular injury. These data
      show that the balanced activity of both G protein-mediated pathways in VSMCs is
      required for an appropriate vessel remodeling response in vascular diseases and
      suggest new approaches to modulate Sm differentiation in vascular pathologies.

PMID- 23129752
TI  - Genetic estimates of population age in the water flea, Daphnia magna.
AB  - Genetic datasets can be used to date evolutionary events, even on recent time
      scales if sufficient data are available. We used statistics calculated from
      multilocus microsatellite datasets to estimate population ages in data generated
      through coalescent simulations and in samples from populations of known age in a
      metapopulation of Daphnia magna in Finland. Our simulation results show that age
      estimates improve with additional loci and define a time frame over which these
      statistics are most useful. On the most recent time scales, assumptions regarding
      the model of mutation (infinite sites vs. stepwise mutation) have little
      influence on estimated ages. In older populations, size homoplasy among
      microsatellite alleles results in a downwards bias for estimates based on the
      infinite sites model (ISM). In the Finnish D. magna metapopulation, our
      genetically derived estimated ages were biased upwards. Potential sources of this
      bias include the underlying model of mutation, gene flow, founder size, and the
      possibility of persistent source populations in the system. Our simulated data
      show that genetic age estimation is possible, even for very young populations,
      but our empirical data highlight the importance of factors such as migration when
      these statistics are applied in natural populations.

PMID- 23129753
TI  - On the role of regulatory T cells during viral-induced inflammatory lesions.
AB  - Ocular HSV-1 infection can result in stromal keratitis, a blinding
      immunoinflammatory lesion that represents an immunopathological response to the
      infection. CD4(+) T cells are the main orchestrators, and lesions are more severe
      if the regulatory T cell (Treg) response is compromised from the onset of
      infection. Little is known about the role of Foxp3(+)CD4(+) Tregs during ongoing
      inflammatory reactions, which is the topic of this article. We used DEREG mice
      and depleted Tregs at different times postinfection. We show that lesions became
      more severe even when depletion was begun in the clinical phase of the disease.
      This outcome was explained both by Tregs' influence on the activity of
      inflammatory effector T cells at the lesion site and by an effect in lymphoid
      tissues that led to reduced numbers of effectors and less trafficking of T cells
      and neutrophils to the eye. Our results demonstrate that Tregs can beneficially
      influence the impact of ongoing tissue-damaging responses to a viral infection
      and imply that therapies boosting Treg function in the clinical phase hold
      promise for controlling a lesion that is an important cause of human blindness.

PMID- 23129754
TI  - IL-7 abrogates suppressive activity of human CD4+CD25+FOXP3+ regulatory T cells
      and allows expansion of alloreactive and autoreactive T cells.
AB  - CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs) control the activation and
      expansion of alloreactive and autoreactive T cell clones. Because uncontrolled
      activation and expansion of autoreactive T cells occur in an IL-7-rich
      environment, we explored the possibility that IL-7 may affect the function of
      Treg. We show that the functional high-affinity IL-7R is expressed on both naive
      and memory Tregs, and exposure to IL-7 results in STAT-5 phosphorylation. Naive,
      but not memory, Tregs proliferated greatly and acquired a memory phenotype in the
      setting of a suppression assay when IL-7 was present. Importantly, the presence
      of IL-7 abrogated the capacity of Tregs to suppress proliferation of conventional
      T cells in response to TCR activators, including alloantigens and autoantigens.
      Removal of IL-7 restored the suppressive function of Tregs. Preblocking of the IL
      7R on the Tregs also restored suppressor function, indicating that IL-7 directly
      affected Treg function. Thus, prolonged periods of homeostatic expansion can
      temporarily release natural regulatory brakes on T cells, thereby providing an
      additional mechanism for activating and expanding alloreactive and autoreactive T
      cells.

PMID- 23129755
TI  - Intrapulmonary G-CSF rescues neutrophil recruitment to the lung and neutrophil
      release to blood in Gram-negative bacterial infection in MCP-1-/- mice.
AB  - We previously demonstrated that MCP-1 is important for E. coli-induced neutrophil
      migration to the lungs. However, E. coli neither disseminates nor induces death
      in mice. Furthermore, the cell types and the host defense mechanisms that
      contribute to MCP-1-dependent neutrophil trafficking have not been defined. In
      this study, we sought to explore the cell types and the mechanisms associated
      with Klebsiella pneumoniae-mediated MCP-1-dependent neutrophil influx. MCP-1(-/-)
      mice are more susceptible to pulmonary K. pneumoniae infection and show higher
      bacterial burden in the lungs and dissemination. MCP-1(-/-) mice also display
      attenuated neutrophil influx, cytokine/chemokine production, and activation of NF
      kappaB and MAPKs following intratracheal K. pneumoniae infection. rMCP-1
      treatment in MCP-1(-/-) mice following K. pneumoniae infection rescued impairment
      in survival, bacterial clearance, and neutrophil accumulation in the lung.
      Neutrophil numbers in the blood of MCP-1(-/-) mice were associated with G-CSF
      concentrations in bronchoalveolar lavage fluid and blood. Bone marrow or resident
      cell-derived MCP-1 contributed to bacterial clearance, neutrophil accumulation,
      and cytokine/chemokine production in the lungs following infection. Furthermore,
      exogenous MCP-1 dose dependently increased neutrophil counts and G-CSF
      concentrations in the blood. Intriguingly, administration of intratracheal rG-CSF
      to MCP-1(-/-) mice after K. pneumoniae infection rescued survival, bacterial
      clearance and dissemination, and neutrophil influx in MCP-1(-/-) mice.
      Collectively, these novel findings unveil an unrecognized role of MCP-1 in
      neutrophil-mediated host immunity during K. pneumoniae pneumonia and illustrate
      that G-CSF could be used to rescue impairment in host immunity in individuals
      with absent or malfunctional MCP-1.

PMID- 23129757
TI  - Determining HIV incidence in populations: moving in the right direction.

PMID- 23129756
TI  - Mannose-capped lipoarabinomannan from Mycobacterium tuberculosis preferentially
      inhibits sphingosine-1-phosphate-induced migration of Th1 cells.
AB  - Chemokine receptor cross-desensitization provides an important mechanism to
      regulate immune cell recruitment at sites of inflammation. We previously reported
      that the mycobacterial cell wall glycophospholipid mannose-capped
      lipoarabinomannan (ManLAM) could induce human peripheral blood T cell chemotaxis.
      Therefore, we examined the ability of ManLAM to desensitize T cells to other
      chemoattractants as a potential mechanism for impaired T cell homing and delayed
      lung recruitment during mycobacterial infection. We found that ManLAM
      pretreatment inhibited in vitro migration of naive human or mouse T cells to the
      lymph node egress signal sphingosine-1-phosphate (S1P). Intratracheal
      administration of ManLAM in mice resulted in significant increases in T cells,
      primarily CCR5(+) (Th1) cells, in lung-draining lymph nodes. To investigate the
      selective CCR5 effect, mouse T cells were differentiated into Th1 or Th2
      populations in vitro, and their ability to migrate to S1P with or without ManLAM
      pretreatment was analyzed. ManLAM pretreatment of Th1 populations inhibited S1P
      induced migration but had no effect on Th2 cell S1P-directed migration,
      suggesting a differential effect by S1P on the two subsets. The PI3K/AKT
      inhibitor Ly294002 inhibited S1P-directed migration by Th1 cells, whereas the ERK
      inhibitor U0126 inhibited Th2 cell S1P-directed migration. These observations
      demonstrate that S1P-induced migratory responses in Th1 and Th2 lymphocytes
      occurs via different signaling pathways and suggests further that the production
      of ManLAM during Mycobacterium tuberculosis infection may function to sequester
      Th1 cells in lung-draining lymph nodes, thereby delaying their recruitment to the
      lung.

PMID- 23129758
TI  - Use of a multifaceted approach to analyze HIV incidence in a cohort study of
      women in the United States: HIV Prevention Trials Network 064 Study.
AB  - BACKGROUND: Reliable methods for estimating the incidence of human
      immunodeficiency virus (HIV) infection are needed to monitor the epidemic,
      identify at-risk populations, and evaluate HIV prevention strategies. We used a
      multifaceted approach to estimate HIV incidence in the HIV Prevention Trials
      Network (HPTN) 064 study. METHODS: The HPTN 064 study enrolled 2067 HIV
      seronegative women and 32 HIV-seropositive women with no prior HIV infection
      diagnosis. Women were followed for up to 12 months. HIV incidence estimates were
      based on (1) detection of acute HIV infection, (2) documentation of HIV
      seroconversion, and (3) detection of recent HIV infection, using a multiassay
      algorithm (MAA). RESULTS: Two women had acute HIV infection at enrollment, 4
      seroconverted, and 2 were identified as recently infected at enrollment using the
      MAA. The annual HIV incidence estimate based on acute infection at enrollment
      (2.52% [95% confidence interval {CI}, .17%-9.33%], using a 14-day window period)
      was higher than the estimate based on seroconversion (0.24% [95% CI, .07%-.62%];
      P = .027). Incidence estimates obtained using the MAA at enrollment and at the
      end of study were 0.25% (95% CI, .03%-.93%) and 0.13% (95% CI, .006%-.76%),
      respectively. CONCLUSIONS: We detected a high frequency of acute infection at
      enrollment. Cross-sectional HIV incidence estimates obtained using the MAA were
      similar to the longitudinal estimate based on HIV seroconversion. CLINICAL TRIALS
      REGISTRATION: NCT00995176.

PMID- 23129759
TI  - Transmission of hepatitis C virus among people who inject drugs: viral stability
      and association with drug preparation equipment.
AB  - BACKGROUND: Hepatitis C virus (HCV) transmission among people who inject drugs
      remains a challenging public health problem. We investigated the risk of HCV
      transmission by analyzing the direct association of HCV with filters, water to
      dilute drugs, and water containers. METHODS: Experiments were designed to
      replicate practices by people who inject drugs and include routinely used
      injection equipment. HCV stability in water was assessed by inoculation of
      bottled water with HCV. Viral association with containers was investigated by
      filling the containers with water, inoculating the water with HCV, emptying the
      water, and refilling the container with fresh water. Transmission risk associated
      with drug preparation filters was determined after drawing virus through a filter
      and incubating the filter to release infectious particles. RESULTS: HCV can
      survive for up to 3 weeks in bottled water. Water containers present a risk for
      HCV transmission, as infectious virions remained associated with water containers
      after washing. Physical properties of the water containers determined the degree
      of HCV contamination after containers were refilled with water. HCV was also
      associated with filter material, in which around 10% of the viral inoculum was
      detectable. CONCLUSIONS: This study demonstrates the potential risk of HCV
      transmission among injection drug users who share water, filters, and water
      containers and will help to define public health interventions to reduce HCV
      transmission.

PMID- 23129760
TI  - HIV incidence determination in the United States: a multiassay approach.
AB  - BACKGROUND: Accurate testing algorithms are needed for estimating human
      immunodeficiency virus (HIV) incidence from cross-sectional surveys. METHODS: We
      developed a multiassay algorithm (MAA) for HIV incidence that includes the BED
      capture enzyme immunoassay (BED-CEIA), an antibody avidity assay, HIV load, and
      CD4(+) T-cell count. We analyzed 1782 samples from 709 individuals in the United
      States who had a known duration of HIV infection (range, 0 to >8 years). Logistic
      regression with cubic splines was used to compare the performance of the MAA to
      the BED-CEIA and to determine the window period of the MAA. We compared the
      annual incidence estimated with the MAA to the annual incidence based on HIV
      seroconversion in a longitudinal cohort. RESULTS: The MAA had a window period of
      141 days (95% confidence interval [CI], 94-150) and a very low false-recent
      misclassification rate (only 0.4% of 1474 samples from subjects infected for >1
      year were misclassified as indicative of recent infection). In a cohort study,
      annual incidence based on HIV seroconversion was 1.04% (95% CI, .70%-1.55%). The
      incidence estimate obtained using the MAA was essentially identical: 0.97% (95%
      CI, .51%-1.71%). CONCLUSIONS: The MAA is as sensitive for detecting recent HIV
      infection as the BED-CEIA and has a very low rate of false-recent
      misclassification. It provides a powerful tool for cross-sectional HIV incidence
      determination.

PMID- 23129761
TI  - Sjogren syndrome antigen B (SSB)/La promotes global microRNA expression by
      binding microRNA precursors through stem-loop recognition.
AB  - MicroRNAs (miRNA) control numerous physiological and pathological processes.
      Typically, the primary miRNA (pri-miRNA) transcripts are processed by nuclear
      Drosha complex into ~70-nucleotide stem-loop precursor miRNAs (pre-miRNA), which
      are further cleaved by cytoplasmic Dicer complex into ~21-nucleotide mature
      miRNAs. However, it is unclear how nascent pre-miRNAs are protected from
      ribonucleases, such as MCPIP1, that degrade pre-miRNAs to abort miRNA production.
      Here, we identify Sjogren syndrome antigen B (SSB)/La as a pre-miRNA-binding
      protein that regulates miRNA processing in vitro. All three RNA-binding motifs
      (LAM, RRM1, and RRM2) of La/SSB are required for efficient pre-miRNA binding.
      Intriguingly, La/SSB recognizes the characteristic stem-loop structure of pre
      miRNAs, of which the majority lack a 3' UUU terminus. Moreover, La/SSB associates
      with endogenous pri-/pre-miRNAs and promotes miRNA biogenesis by stabilizing pre
      miRNAs from nuclease (e.g. MCPIP1)-mediated decay in mammalian cells.
      Accordingly, we observed positive correlations between the expression status of
      La/SSB and Dicer in human cancer transcriptome and prognosis. These studies
      identify an important function of La/SSB as a global regulator of miRNA
      expression, and implicate stem-loop recognition as a major mechanism that
      mediates association between La/SSB and diverse RNA molecules.

PMID- 23129762
TI  - Identification of three residues essential for 5-hydroxytryptamine 2A
      metabotropic glutamate 2 (5-HT2A.mGlu2) receptor heteromerization and its
      psychoactive behavioral function.
AB  - Serotonin and glutamate G protein-coupled receptor (GPCR) neurotransmission
      affects cognition and perception in humans and rodents. GPCRs are capable of
      forming heteromeric complexes that differentially alter cell signaling, but the
      role of this structural arrangement in modulating behavior remains unknown. Here,
      we identified three residues located at the intracellular end of transmembrane
      domain four that are necessary for the metabotropic glutamate 2 (mGlu2) receptor
      to be assembled as a GPCR heteromer with the serotonin 5-hydroxytryptamine 2A (5
      HT(2A)) receptor in the mouse frontal cortex. Substitution of these residues (Ala
      677(4.40), Ala-681(4.44), and Ala-685(4.48)) leads to absence of 5-HT(2A).mGlu2
      receptor complex formation, an effect that is associated with a decrease in their
      heteromeric ligand binding interaction. Disruption of heteromeric expression with
      mGlu2 attenuates the psychosis-like effects induced in mice by hallucinogenic 5
      HT(2A) agonists. Furthermore, the ligand binding interaction between the
      components of the 5-HT(2A).mGlu2 receptor heterocomplex is up-regulated in the
      frontal cortex of schizophrenic subjects as compared with controls. Together,
      these findings provide structural evidence for the unique behavioral function of
      a GPCR heteromer.

PMID- 23129763
TI  - The F-BAR protein PACSIN2 regulates epidermal growth factor receptor
      internalization.
AB  - Signaling via growth factor receptors, including the epidermal growth factor
      (EGF) receptor, is key to various cellular processes, such as proliferation, cell
      survival, and cell migration. In a variety of human diseases such as cancer,
      aberrant expression and activation of growth factor receptors can lead to
      disturbed signaling. Intracellular trafficking is crucial for proper signaling of
      growth factor receptors. As a result, the level of cell surface expression of
      growth factor receptors is an important determinant for the outcome of downstream
      signaling. BAR domain-containing proteins represent an important family of
      proteins that regulate membrane dynamics. In this study, we identify a novel role
      for the F-BAR protein PACSIN2 in the regulation of EGF receptor signaling. We
      show that internalized EGF as well as the (activated) EGF receptor translocated
      to PACSIN2-positive endosomes. Furthermore, loss of PACSIN2 increased plasma
      membrane expression of the EGF receptor in resting cells and increased EGF
      induced phosphorylation of the EGF receptor. As a consequence, EGF-induced
      activation of Erk and Akt as well as cell proliferation were enhanced in PACSIN2
      depleted cells. In conclusion, this study identifies a novel role for the F-BAR
      domain protein PACSIN2 in regulating EGF receptor surface levels and EGF-induced
      downstream signaling.

PMID- 23129764
TI  - The glaucoma-associated olfactomedin domain of myocilin is a novel calcium
      binding protein.
AB  - Myocilin is a protein found in the trabecular meshwork extracellular matrix
      tissue of the eye that plays a role in regulating intraocular pressure. Both wild
      type and certain myocilin variants containing mutations in the olfactomedin (OLF)
      domain are linked to the optic neuropathy glaucoma. Because calcium ions are
      important biological cofactors that play numerous roles in extracellular matrix
      proteins, we examined the calcium binding properties of the myocilin OLF domain
      (myoc-OLF). Our study reveals an unprecedented high affinity calcium binding site
      within myoc-OLF. The calcium ion remains bound to wild-type OLF at neutral and
      acidic pH. A glaucoma-causing OLF variant, myoc-OLF(D380A), is calcium-depleted.
      Key differences in secondary and tertiary structure between myoc-OLF(D380A) and
      wild-type myoc-OLF, as well as limited access to chelators, indicate that the
      calcium binding site is largely buried in the interior of the protein. Analysis
      of six conserved aspartate or glutamate residues and an additional 18 disease
      causing variants revealed two other candidate residues that may be involved in
      calcium coordination. Our finding expands our knowledge of calcium binding in
      extracellular matrix proteins; provides new clues into domain structure,
      function, and pathogenesis for myocilin; and offers insights into highly
      conserved, biomedically relevant OLF domains.

PMID- 23129765
TI  - Contrasting effects of alpha-synuclein and gamma-synuclein on the phenotype of
      cysteine string protein alpha (CSPalpha) null mutant mice suggest distinct
      function of these proteins in neuronal synapses.
AB  - In neuronal synapses, neurotransmitter-loaded vesicles fuse with presynaptic
      plasma membrane in a complex sequence of tightly regulated events. The assembly
      of specialized SNARE complexes plays a pivotal role in this process. The function
      of the chaperone cysteine string protein alpha (CSPalpha) is important for
      synaptic SNARE complex formation, and mice lacking this protein develop severe
      synaptic dysfunction and neurodegeneration that lead to their death within 3
      months after birth. Another presynaptic protein, alpha-synuclein, also
      potentiates SNARE complex formation, and its overexpression rescues the phenotype
      of CSPalpha null mutant mice, although these two proteins use different
      mechanisms to achieve this effect. alpha-Synuclein is a member of a family of
      three related proteins whose structural similarity suggests functional
      redundancy. Here, we assessed whether gamma-synuclein shares the ability of alpha
      synuclein to bind synaptic vesicles and ameliorate neurodegeneration caused by
      CSPalpha deficiency in vivo. Although the N-terminal lipid-binding domains of the
      two synucleins showed similar affinity for purified synaptic vesicles, the C
      terminal domain of gamma-synuclein was not able to interact with synaptobrevin
      2/VAMP2. Consequently, overexpression of gamma-synuclein did not have any
      noticeable effect on the phenotype of CSPalpha null mutant mice. Our data suggest
      that the functions of alpha- and gamma-synucleins in presynaptic terminals are
      not fully redundant.

PMID- 23129766
TI  - The ubiquitin ligase synoviolin up-regulates amyloid beta production by targeting
      a negative regulator of gamma-secretase, Rer1, for degradation.
AB  - Alzheimer's disease is characterized by the deposition of Abeta, which is
      generated from the amyloid precursor protein through its cleavage by beta- and
      gamma-secretases. The gamma-secretase complex component nicastrin (NCT) plays
      significant roles in the assembly and proper trafficking of the gamma-secretase
      complex and in the recognition of amyloid precursor protein. NCT is incorporated
      into the gamma-secretase complex in the endoplasmic reticulum (ER) and
      glycosylated in the Golgi. In contrast, unassembled NCT is retrieved or retained
      in the ER by the protein Retention in endoplasmic reticulum 1 (Rer1). We reported
      previously that synoviolin (Syvn), an E3 ubiquitin ligase, degrades NCT and
      affects the generation of Abeta. Here, we examined in more detail the effect of
      Syvn on the generation of Abeta. We found that overexpression of a dominant
      negative form of Syvn (C307A mutant) and a Syvn-RNAi decreased the generation of
      Abeta. These results indicate that the ubiquitin ligase activity of Syvn up
      regulates the generation of Abeta. We hypothesized, therefore, that Syvn
      regulates the assembly or localization of the gamma-secretase complex by
      ubiquitinating Rer1, resulting in its subsequent degradation. Our findings that
      the level of Rer1 was increased in Syvn knockout fibroblasts because of
      inhibition of its degradation support this hypothesis. Moreover, we found that
      Rer1 interacts with Syvn in the ER, is ubiquitinated by Syvn, and is then
      degraded via the proteasome or lysosomal pathways. Finally, we showed that
      localization of mature NCT to the plasma membrane as well as gamma-secretase
      complex levels are decreased in fibroblasts of Syvn knockout mice. Thus, it is
      likely that Syvn regulates the assembly of the gamma-secretase complex via the
      degradation of Rer1, which results in the generation of Abeta.

PMID- 23129767
TI  - Functional and structural insights of a Staphylococcus aureus apoptotic-like
      membrane peptide from a toxin-antitoxin module.
AB  - We report a functional type I toxin-antitoxin (TA) module expressed by a human
      pathogen, Staphylococcus aureus. TA systems consist of stable toxins and labile
      antitoxins encoded within small genetic modules widespread in eubacteria and
      archaea. TA genes provide stress adaptation and protection against DNA loss or
      invasion. The genes encoding the SprA1 toxic peptide (PepA1) and the SprA1(AS)
      RNA antitoxin are within a pathogenicity island on opposite strands and possess a
      3' overlap. To prevent peptide toxicity during S. aureus growth, PepA1 expression
      from stable (half-life > 3 h) SprA1 is repressed by elevated amounts of unstable
      (half-life = ~10 mn) SprA1(AS). In vivo, PepA1 localizes at the bacterial
      membrane and triggers S. aureus death. Based on NMR and CD data, its solution
      structure was solved and is a long bent, interrupted helix. Molecular dynamics
      simulations indicate that PepA1 compaction and helical content fluctuate in
      accordance with its cytoplasm or membrane location. When inserted into the S.
      aureus membrane, the PepA1 conformation switches to a ~7-nm-long continuous
      helix, presumably forming pores to alter membrane integrity. PepA1 expression is
      induced upon acidic and oxidative stresses by reducing SprA1(AS) levels. As an
      altruistic behavior during infection, some cells may induce the expression of
      that toxin that would facilitate departure from the host immune cells for
      spreading.

PMID- 23129768
TI  - A subset of mixed lineage leukemia proteins has plant homeodomain (PHD)-mediated
      E3 ligase activity.
AB  - The mixed lineage leukemia protein MLL1 contains four highly conserved plant
      homeodomain (PHD) fingers, which are invariably deleted in oncogenic MLL1 fusion
      proteins in human leukemia. Here we show that the second PHD finger (PHD2) of
      MLL1 is an E3 ubiquitin ligase in the presence of the E2-conjugating enzyme
      CDC34. This activity is conserved in the second PHD finger of MLL4, the closest
      homolog to MLL1 but not in MLL2 or MLL3. Mutation of PHD2 leads to MLL1
      stabilization, as well as increased transactivation ability and MLL1 recruitment
      to the target gene loci, suggesting that PHD2 negatively regulates MLL1 activity.

PMID- 23129769
TI  - Construction of a chondroitin sulfate library with defined structures and
      analysis of molecular interactions.
AB  - Chondroitin sulfate (CS) is a linear acidic polysaccharide, composed of repeating
      disaccharide units of glucuronic acid and N-acetyl-D-galactosamine and modified
      with sulfate residues at different positions, which plays various roles in
      development and disease. Here, we chemo-enzymatically synthesized various CS
      species with defined lengths and defined sulfate compositions, from chondroitin
      hexasaccharide conjugated with hexamethylenediamine at the reducing ends, using
      bacterial chondroitin polymerase and recombinant CS sulfotransferases, including
      chondroitin-4-sulfotransferase 1 (C4ST-1), chondroitin-6-sulfotransferase 1 (C6ST
      1), N-acetylgalactosamine 4-sulfate 6-sulfotransferase (GalNAc4S-6ST), and
      uronosyl 2-sulfotransferase (UA2ST). Sequential modifications of CS with a series
      of CS sulfotransferases revealed their distinct features, including their
      substrate specificities. Reactions with chondroitin polymerase generated non
      sulfated chondroitin, and those with C4ST-1 and C6ST-1 generated uniformly
      sulfated CS containing >95% 4S and 6S units, respectively. GalNAc4S-6ST and UA2ST
      generated highly sulfated CS possessing ~90% corresponding disulfated
      disaccharide units. Sequential reactions with UA2ST and GalNAc4S-6ST generated
      further highly sulfated CS containing a mixed structure of disulfated units.
      Surprisingly, sequential reactions with GalNAc4S-6ST and UA2ST generated a novel
      CS molecule containing ~29% trisulfated disaccharide units. Enzyme-linked
      immunosorbent assay and surface plasmon resonance analysis using the CS library
      and natural CS products modified with biotin at the reducing ends, revealed
      details of the interactions of CS species with anti-CS antibodies, and with CS
      binding molecules such as midkine and pleiotrophin. Chemo-enzymatic synthesis
      enables the generation of CS chains of the desired lengths, compositions, and
      distinct structures, and the resulting library will be a useful tool for studies
      of CS functions.

PMID- 23129770
TI  - FlaX, a unique component of the crenarchaeal archaellum, forms oligomeric ring
      shaped structures and interacts with the motor ATPase FlaI.
AB  - Archaella are the archaeal motility structure, which are structurally similar to
      gram-negative bacterial type IV pili but functionally resemble bacterial
      flagella. Structural and biochemical data of archaellum subunits are missing.
      FlaX, a conserved subunit in crenarchaeal archaella, formed high molecular weight
      complexes that adapted a ring-like structure with an approximate diameter of 30
      nm. The C terminus of FlaX was not only involved in the oligomerization, but also
      essential for FlaX interaction with FlaI, the bifunctional ATPase that is
      involved in assembly and rotation of the archaellum. This study gives first
      insights in the assembly apparatus of archaella.

PMID- 23129771
TI  - The Hect domain E3 ligase Tom1 and the F-box protein Dia2 control Cdc6
      degradation in G1 phase.
AB  - The accurate replication of genetic information is critical to maintaining
      chromosomal integrity. Cdc6 functions in the assembly of pre-replicative
      complexes and is specifically required to load the Mcm2-7 replicative helicase
      complex at replication origins. Cdc6 is targeted for protein degradation by
      multiple mechanisms in Saccharomyces cerevisiae, although only a single pathway
      and E3 ubiquitin ligase for Cdc6 has been identified, the SCF(Cdc4) (Skp1/Cdc53/F
      box protein) complex. Notably, Cdc6 is unstable during the G(1) phase of the cell
      cycle, but the ubiquitination pathway has not been previously identified. Using a
      genetic approach, we identified two additional E3 ubiquitin ligase components
      required for Cdc6 degradation, the F-box protein Dia2 and the Hect domain E3
      Tom1. Both Dia2 and Tom1 control Cdc6 turnover during G(1) phase of the cell
      cycle and act separately from SCF(Cdc4). Ubiquitination of Cdc6 is significantly
      reduced in dia2Delta and tom1Delta cells. Tom1 and Dia2 each independently
      immunoprecipitate Cdc6, binding to a C-terminal region of the protein. Tom1 and
      Dia2 cannot compensate for each other in Cdc6 degradation. Cdc6 and Mcm4
      chromatin association is aberrant in tom1Delta and dia2Delta cells in G(1) phase.
      Together, these results present evidence for a novel degradation pathway that
      controls Cdc6 turnover in G(1) that may regulate pre-replicative complex
      assembly.

PMID- 23129772
TI  - Cysteine 70 of ankyrin-G is S-palmitoylated and is required for function of
      ankyrin-G in membrane domain assembly.
AB  - Ankyrin-G (AnkG) coordinates protein composition of diverse membrane domains,
      including epithelial lateral membranes and neuronal axon initial segments.
      However, how AnkG itself localizes to these membrane domains is not understood.
      We report that AnkG remains on the plasma membrane in Madin-Darby canine kidney
      (MDCK) cells grown in low calcium, although these cells lack apical-basal
      polarity and exhibit loss of plasma membrane association of AnkG partners, E
      cadherin and beta(2)-spectrin. We subsequently demonstrate using mutagenesis and
      mass spectrometry that AnkG is S-palmitoylated exclusively at Cys-70, which is
      located in a loop of the first ankyrin repeat and is conserved in the vertebrate
      ankyrin family. Moreover, C70A mutation abolishes membrane association of 190-kDa
      AnkG in MDCK cells grown in low calcium. C70A 190-kDa AnkG fails to restore
      biogenesis of epithelial lateral membranes in MDCK cells depleted of endogenous
      AnkG. In addition, C70A 270-kDa AnkG fails to cluster at the axon initial segment
      of AnkG-depleted cultured hippocampal neurons and fails to recruit neurofascin as
      well as voltage-gated sodium channels. These effects of C70A mutation combined
      with evidence for its S-palmitoylation are consistent with a requirement of
      palmitoylation for targeting and function of AnkG in membrane domain biogenesis
      at epithelial lateral membranes and neuronal axon initial segments.

PMID- 23129773
TI  - Cyclotides insert into lipid bilayers to form membrane pores and destabilize the
      membrane through hydrophobic and phosphoethanolamine-specific interactions.
AB  - Cyclotides are a family of plant-derived circular proteins with potential
      therapeutic applications arising from their remarkable stability, broad sequence
      diversity, and range of bioactivities. Their membrane-binding activity is
      believed to be a critical component of their mechanism of action. Using
      isothermal titration calorimetry, we studied the binding of the prototypical
      cyclotides kalata B1 and kalata B2 (and various mutants) to dodecylphosphocholine
      micelles and phosphoethanolamine-containing lipid bilayers. Although binding is
      predominantly an entropy-driven process, suggesting that hydrophobic forces
      contribute significantly to cyclotide-lipid complex formation, specific binding
      to the phosphoethanolamine-lipid headgroup is also required, which is evident
      from the enthalpic changes in the free energy of binding. In addition, using a
      combination of dissipative quartz crystal microbalance measurements and neutron
      reflectometry, we elucidated the process by which cyclotides interact with
      bilayer membranes. Initially, a small number of cyclotides bind to the membrane
      surface and then insert first into the outer membrane leaflet followed by
      penetration through the membrane and pore formation. At higher concentrations of
      cyclotides, destabilization of membranes occurs. Our results provide significant
      mechanistic insight into how cyclotides exert their bioactivities.

PMID- 23129774
TI  - Atg9 vesicles recruit vesicle-tethering proteins Trs85 and Ypt1 to the
      autophagosome formation site.
AB  - Atg9 is a transmembrane protein that is essential for autophagy. In the budding
      yeast Saccharomyces cerevisiae, it has recently been revealed that Atg9 exists on
      cytoplasmic small vesicles termed Atg9 vesicles. To identify the components of
      Atg9 vesicles, we purified the Atg9 vesicles and subjected them to mass
      spectrometry. We found that their protein composition was distinct from other
      organellar membranes and that Atg9 and Atg27 in particular are major components
      of Atg9 vesicles. In addition to these two components, Trs85, a specific subunit
      of the transport protein particle III (TRAPPIII) complex, and the Rab GTPase Ypt1
      were also identified. Trs85 directly interacts with Atg9, and the Trs85
      containing TRAPPIII complex facilitates the association of Ypt1 onto Atg9
      vesicles. We also showed that Trs85 and Ypt1 are localized to the
      preautophagosomal structure in an Atg9-dependent manner. Our data suggest that
      Atg9 vesicles recruit the TRAPPIII complex and Ypt1 to the preautophagosomal
      structure. The vesicle-tethering machinery consequently acts in the process of
      autophagosome formation.

PMID- 23129775
TI  - Tau oligomers impair artificial membrane integrity and cellular viability.
AB  - The microtubule-associated protein Tau is mainly expressed in neurons, where it
      binds and stabilizes microtubules. In Alzheimer disease and other tauopathies,
      Tau protein has a reduced affinity toward microtubules. As a consequence, Tau
      protein detaches from microtubules and eventually aggregates into beta-sheet
      containing filaments. The fibrillization of monomeric Tau to filaments is a
      multistep process that involves the formation of various aggregates, including
      spherical and protofibrillar oligomers. Previous concepts, primarily developed
      for Abeta and alpha-synuclein, propose these oligomeric intermediates as the
      primary cytotoxic species mediating their deleterious effects through membrane
      permeabilization. In the present study, we thus analyzed whether this concept can
      also be applied to Tau protein. To this end, viability and membrane integrity
      were assessed on SH-SY5Y neuroblastoma cells and artificial phospholipid
      vesicles, treated with Tau monomers, Tau aggregation intermediates, or Tau
      fibrils. Our findings suggest that oligomeric Tau aggregation intermediates are
      the most toxic compounds of Tau fibrillogenesis, which effectively decrease cell
      viability and increase phospholipid vesicle leakage. Our data integrate Tau
      protein into the class of amyloidogenic proteins and enforce the hypothesis of a
      common toxicity-mediating mechanism for amyloidogenic proteins.

PMID- 23129776
TI  - The exosome secretory pathway transports amyloid precursor protein carboxyl
      terminal fragments from the cell into the brain extracellular space.
AB  - In vitro studies have shown that neuronal cell cultures secrete exosomes
      containing amyloid-beta precursor protein (APP) and the APP-processing products,
      C-terminal fragments (CTFs) and amyloid-beta (Abeta). We investigated the
      secretion of full-length APP (flAPP) and APP CTFs via the exosome secretory
      pathway in vivo. To this end, we developed a novel protocol designed to isolate
      exosomes secreted into mouse brain extracellular space. Exosomes with typical
      morphology were isolated from freshly removed mouse brains and from frozen mouse
      and human brain tissues, demonstrating that exosomes can be isolated from post
      mortem tissue frozen for long periods of time. flAPP, APP CTFs, and enzymes that
      cleave both flAPP and APP CTFs were identified in brain exosomes. Although higher
      levels of both flAPP and APP CTFs were observed in exosomes isolated from the
      brains of transgenic mice overexpressing human APP (Tg2576) compared with wild
      type control mice, there was no difference in the number of secreted brain
      exosomes. These data indicate that the levels of flAPP and APP CTFs associated
      with exosomes mirror the cellular levels of flAPP and APP CTFs. Interestingly,
      exosomes isolated from the brains of both Tg2576 and wild-type mice are enriched
      with APP CTFs relative to flAPP. Thus, we hypothesize that the exosome secretory
      pathway plays a pleiotropic role in the brain: exosome secretion is beneficial to
      the cell, acting as a specific releasing system of neurotoxic APP CTFs and Abeta,
      but the secretion of exosomes enriched with APP CTFs, neurotoxic proteins that
      are also a source of secreted Abeta, is harmful to the brain.

PMID- 23129777
TI  - Tumor necrosis factor-stimulated gene-6 (TSG-6) amplifies hyaluronan synthesis by
      airway smooth muscle cells.
AB  - We tested the hypothesis that the artificial addition of heavy chains from inter
      alpha-inhibitor to hyaluronan (HA), by adding recombinant TSG-6 (TNF-stimulated
      gene-6) to the culture medium of murine airway smooth muscle (MASM) cells, would
      enhance leukocyte binding to HA cables produced in response to poly(I:C). As
      predicted, the addition of heavy chains to HA cables enhanced leukocyte adhesion
      to these cables, but it also had several unexpected effects. (i) It produced
      thicker, more pronounced HA cables. (ii) It increased the accumulation of HA in
      the cell-associated matrix. (iii) It decreased the amount of HA in the
      conditioned medium. Importantly, these effects were observed only when TSG-6 was
      administered in the presence of poly(I:C), and TSG-6 did not exert any effect on
      its own. Increased HA synthesis occurred during active, poly(I:C)-induced HA
      synthesis and did not occur when TSG-6 was added after poly(I:C)-induced HA
      synthesis was complete. MASM cells derived from TSG-6(-/-), HAS1/3(-/-), and
      CD44(-/-) mice amplified HA synthesis in response to poly(I:C) + TSG-6 in a
      manner similar to WT MASM cells, demonstrating that they are expendable in this
      process. We conclude that TSG-6 increases the accumulation of HA in the cell
      associated matrix, partially by preventing its dissolution from the cell
      associated matrix into the conditioned medium, but primarily by inducing HA
      synthesis.

PMID- 23129778
TI  - Ki-67 index guided selection of preoperative chemotherapy for HER2-positive
      breast cancer: a randomized phase II trial.
AB  - Changes in Ki-67 may be a useful predictor of efficacy for preoperative therapy
      in breast cancer. This randomized Phase II trial will compare standard
      preoperative chemotherapy comprising paclitaxel and trastuzumab with Ki-67 index
      guided preoperative chemotherapy in patients with human epidermal growth factor
      receptor 2-positive operable breast cancer. In the Ki-67 index guided therapy,
      paclitaxel and trastuzumab were administered initially and the Ki-67 index is
      evaluated from biopsied specimens after 2 weeks of preoperative chemotherapy. The
      subsequent chemotherapy regimen is modified according to changes in the Ki-67
      index from the start of therapy. If the Ki-67 index is reduced as expected,
      paclitaxel and trastuzumab are continued. If the Ki-67 index is not reduced as
      expected, the chemotherapy regimen is changed to epirubicin, cyclophosphamide and
      trastuzumab. The primary endpoint is the rate of pathological complete response.
      The secondary endpoints are the objective response rate, disease-free survival
      and overall survival. Two hundred patients were planned to be accrued.

PMID- 23129779
TI  - A new, long-wavelength borondipyrromethene sphingosine for studying sphingolipid
      dynamics in live cells.
AB  - Sphingolipids function as cell membrane components and as signaling molecules
      that regulate critical cellular processes. To study unacylated and acylated
      sphingolipids in cells with fluorescence microscopy, the fluorophore in the
      analog must be located within the sphingoid backbone and not the N-acyl fatty
      acid side chain. Although such fluorescent sphingosine analogs have been
      reported, they either require UV excitation or their emission overlaps with that
      of the most common protein label, green fluorescent protein (GFP). We report the
      synthesis and use of a new fluorescent sphingolipid analog, borondipyrromethene
      (BODIPY) 540 sphingosine, which has an excitation maximum at 540 nm and emission
      that permits its visualization in parallel with GFP. Mammalian cells readily
      metabolized BODIPY 540 sphingosine to more complex fluorescent sphingolipids, and
      subsequently degraded these fluorescent sphingolipids via the native sphingolipid
      catabolism pathway. Visualization of BODIPY 540 fluorescence in parallel with GFP
      labeled organelle-specific proteins showed the BODIPY 540 sphingosine metabolites
      were transported through the secretory pathway and were transiently located
      within lysosomes, mitochondria, and the nucleus. The reported method for using
      BODIPY 540 sphingosine to visualize sphingolipids in parallel with GFP-labeled
      proteins within living cells may permit new insight into sphingolipid transport,
      metabolism, and signaling.

PMID- 23129780
TI  - In memoriam: Dr. Francesc Abel Fabre, S.J.

PMID- 23129782
TI  - Fibroblast growth factor-21 serum concentrations are associated with metabolic
      and hepatic markers in humans.
AB  - Rather than a traditional growth factor, fibroblast growth factor-21 (FGF21) is
      considered to be a metabolic hormone. In the current study, we investigated serum
      FGF21 levels in the self-contained population of Sorbs. Serum FGF21
      concentrations were quantified by ELISA and correlated with IGF1 as well as
      metabolic, renal, hepatic, inflammatory, and cardiovascular parameters in 913
      Sorbs from Germany. Moreover, human IGF1 protein secretion was investigated in
      FGF21-stimulated HepG2 cells. Median FGF21 serum concentrations were 2.1-fold
      higher in subjects with type 2 diabetes mellitus (141.8 ng/l) compared with
      controls (66.7 ng/l). Furthermore, nondiabetic subjects with FGF21 levels below
      the detection limit of the ELISA showed a more beneficial metabolic profile
      compared with subjects with measurable FGF21. Moreover, FGF21 was significantly
      lower in female compared with male subjects after adjustment for age and BMI. In
      multiple regression analyses, circulating FGF21 concentrations remained
      independently and positively associated with gender, systolic blood pressure,
      triglycerides, and gamma glutamyl transferase whereas a negative association was
      observed with IGF1 in nondiabetic subjects. Notably, FGF21 significantly
      inhibited IGF1 secretion into HepG2 cell culture supernatants in preliminary in
      vitro experiments. FGF21 serum concentrations are associated with facets of the
      metabolic syndrome, hepatocellular function, as well as GH status.

PMID- 23129781
TI  - Infrequent SCN9A mutations in congenital insensitivity to pain and
      erythromelalgia.
AB  - OBJECTIVE: Mutations in SCN9A have been reported in (1) congenital insensitivity
      to pain (CIP); (2) primary erythromelalgia; (3) paroxysmal extreme pain disorder;
      (4) febrile seizures and recently (5) small fibre sensory neuropathy. We sought
      to investigate for SCN9A mutations in a clinically well-characterised cohort of
      patients with CIP and erythromelalgia. METHODS: We sequenced all exons of SCN9A
      in 19 clinically well-studied cases including 6 CIP and 13 erythromelalgia (9
      with family history, 10 with small-fibre neuropathy). The identified variants
      were assessed in dbSNP135, 1K genome, NHLBI-Exome Sequencing Project (5400
      exomes) databases, and 768 normal chromosomes. RESULTS: In erythromelalgia case
      7, we identified a novel Q10>K mutation. In CIP case 6, we identified a novel, de
      novo splicing mutation (IVS8-2A>G); this splicing mutation compounded with a
      nonsense mutation (R523>X) and abolished SCN9A mRNA expression almost completely
      compared with his unaffected father. In CIP case 5, we found a variant (P610>T)
      previously considered causal for erythromelalgia, supporting recently raised
      doubt on its causal nature. We also found a splicing junction variant (IVS24
      7delGTTT) in all 19 patients, this splicing variant was previously considered
      casual for CIP, but IVS24-7delGTTT was in fact the major allele in Caucasian
      populations. CONCLUSIONS: Two novel SCN9A mutations were identified, but
      frequently polymorphism variants are found which may provide susceptibility
      factors in pain modulation. CIP and erythromelalgia are defined as genetically
      heterogeneous, and some SCN9A variants previously considered causal may only be
      modifying factors.

PMID- 23129784
TI  - A comment about the correct attribution of the discovery of FX Friuli disorder.

PMID- 23129783
TI  - Postexposure application of Fas receptor small-interfering RNA to suppress sulfur
      mustard-induced apoptosis in human airway epithelial cells: implication for a
      therapeutic approach.
AB  - Sulfur mustard (SM) is a vesicant chemical warfare and terrorism agent. Besides
      skin and eye injury, respiratory damage has been mainly responsible for morbidity
      and mortality after SM exposure. Previously, it was shown that suppressing the
      death receptor (DR) response by the dominant-negative Fas-associated death domain
      protein prior to SM exposure blocked apoptosis and microvesication in skin. Here,
      we studied whether antagonizing the Fas receptor (FasR) pathway by small
      interfering RNA (siRNA) applied after SM exposure would prevent apoptosis and,
      thus, airway injury. Normal human bronchial/tracheal epithelial (NHBE) cells were
      used as an in vitro model with FasR siRNA, FasR agonistic antibody CH11, and FasR
      antagonistic antibody ZB4 as investigative tools. In NHBE cells, both SM (300 uM)
      and CH11 (100 ng/ml) induced caspase-3 activation, which was inhibited by FasR
      siRNA and ZB4, indicating that SM-induced apoptosis was via the Fas response.
      FasR siRNA inhibited SM-induced caspase-3 activation when added to NHBE cultures
      up to 8 hours after SM. Results using annexin V/propidium iodide-stained cells
      showed that both apoptosis and necrosis were involved in cell death due to SM;
      FasR siRNA decreased both apoptotic and necrotic cell populations.
      Bronchoalveolar lavage fluid (BALF) of rats exposed to SM (1 mg/kg, 50 minutes)
      revealed a significant (P < 0.05) increase in soluble Fas ligand and active
      caspase-3 in BALF cells. These findings suggest an intervention of Fas-mediated
      apoptosis as a postexposure therapeutic strategy with a therapeutic window for SM
      inhalation injury and possibly other respiratory diseases involving the Fas
      response.

PMID- 23129785
TI  - Is mean platelet volume a predictive marker in patients with venous thrombosis?

PMID- 23129786
TI  - Living with chronic pancreatitis: a qualitative study.
AB  - OBJECTIVE: Recent literature acknowledges the impact of this progressive and
      debilitating disease on psychological and social well-being, but the plight of
      those with chronic pancreatitis remains unknown and hidden. The aim of this study
      was to develop an understanding of what it means to live with chronic
      pancreatitis. DESIGN: Qualitative study based on philosophical hermeneutics using
      multiple unstructured interviews. PARTICIPANTS: Fourteen people with chronic
      pancreatitis and five relatives took part in 41 interviews in 2007-2008. SETTING:
      Tertiary clinic in Ireland. RESULTS: The meaning of living with chronic
      pancreatitis for participants in this study is 'enduring disruption'. Enduring
      has a two-fold meaning; it symbolises the perpetual or permanent nature of
      disruption that occurs at physiological, social and psychological levels (i.e.,
      'suffering'). Enduring also means 'to tolerate' and encompasses how the
      participants and their families cope and manage the overall transition from well
      person to a person with chronic pancreatitis. DISCUSSION: This study offers an
      alternative perspective to previous quality of life research and presents a
      challenge to the emphasis on management of the pathophysiological processes and
      treatment of chronic pancreatitis that is decontextualised from the person's
      everyday living. Healthcare professionals need to understand and support people
      with chronic pancreatitis.

PMID- 23129787
TI  - Chronic pain management strategies used by low-income overweight Latinos.
AB  - OBJECTIVE: The objective of this study is to examine the strategies used to
      manage chronic pain from the perspective of the individual in group interviews.
      METHODS: Sixteen low-income overweight Latino adults participated in two group
      interviews facilitated by a trained moderator who inquired about the type of
      chronic pain suffered by participants, followed by more specific questions about
      pain management. Interviews were audio-recorded, transcribed verbatim (Spanish),
      back-translated into English, and analyzed using thematic analysis. RESULTS:
      Participants' pain varied in type, location, and intensity. Participants
      discussed pain-related changes in activities and social life, and difficulties
      with health care providers, and as a result, we discovered five major themes:
      pain-related life alterations, enduring the pain, trying different strategies,
      emotional suffering, and encounters with health care system/providers.
      DISCUSSION: Findings indicated that there are opportunities for providers to
      improve care for low-income overweight Latinos with chronic pain by listening
      respectfully to how pain alters their daily lives and assisting them in feasible
      self-management strategies.

PMID- 23129788
TI  - Translating new knowledge into practices: reconceptualising stroke as an
      emergency condition.
AB  - OBJECTIVES To examine how the new concept of stroke as an emergency condition led
      to the development of new clinical pathways for stroke patients in Newcastle Upon
      Tyne, implemented through protocols which were then rapidly adopted across the UK
      and further afield. METHODS Historical analysis using health policy documents,
      published papers and correspondence on stroke alongside 17 interviews with stroke
      clinicians and managers in the UK and the US. RESULTS The challenges of
      implementation stemmed from organisational and professional barriers rather than
      scientific or technological difficulties. Stroke's historical status as a non
      treatable illness was a barrier to the adoption of acute treatments. Building new
      pathways for stroke patients by developing protocols for paramedics and emergency
      room staff originated as a local solution to a local problem but were taken up
      widely. DISCUSSION Understanding the clinical response to the reconceptualisation
      of stroke as a treatable disease contributes to our understandings of the
      relations between clinical research and practice. These findings have
      implications for how we understand the translation of new knowledge into practice
      and its transfer across different clinical communities and settings. Protocols
      are shown to be a particularly valuable tool, bridging knowledge between
      communities and manifesting a new identity for stroke. 

PMID- 23129789
TI  - Preserved fertility despite erectile dysfunction in mice lacking the nitric oxide
      receptor.
AB  - Nitric oxide (NO) and cGMP have been shown to be important mediators of penile
      erection. Erectile dysfunction may result from reduced or non-functional signal
      transduction within this cascade. There is, however, some inconsistency in the
      available data as mice lacking NO synthases (endothelial and neuronal nitric
      oxide synthase, or both) appear to be fertile whereas mice deficient in cGMP
      dependent protein kinase I (PKGI) suffer from erectile dysfunction. To clarify
      this discrepancy we performed studies on mice lacking the NO receptor NO
      sensitive guanylyl cyclase (NO-GC). In addition, we generated cell-specific NO-GC
      knockout (KO) lines to investigate the function of NO in individual cell types.
      NO-GC was specifically deleted in smooth muscle or endothelial cells (SM-guanylyl
      cyclase knockout (SM-GCKO) and EC-GCKO, respectively) and these KO lines were
      compared with total knockouts (GCKO) and wild-type animals. We investigated
      expression of NO-GC, NO-induced relaxation of corpus cavernosum smooth muscle and
      their ability to generate offspring. NO-GC-positive immunostaining was detected
      in smooth muscle and endothelial cells of murine corpus cavernosum but not in
      interstitial cells of Cajal. NO released from NO donors as well as from nitrergic
      neurons failed to relax precontracted corpus cavernosum from GCKO mice in organ
      bath experiments. Similar results were obtained in corpus cavernosum from SM-GCKO
      mice whereas deletion of NO-GC in endothelial cells did not affect relaxation.
      The lack of NO-induced relaxation in GCKO animals was not compensated for by
      guanosine 3,5-cyclic monophosphate (cGMP) signalling. To our surprise, GCKO males
      were fertile although their ability to produce offspring was decreased. Our data
      show that deletion of NO-GC specifically in smooth muscle cells abolishes NO
      induced corpus cavernosum relaxation but does not lead to infertility.

PMID- 23129790
TI  - Sprint interval and traditional endurance training increase net intramuscular
      triglyceride breakdown and expression of perilipin 2 and 5.
AB  - Intramuscular triglyceride (IMTG) utilization is enhanced by endurance training
      (ET) and is linked to improved insulin sensitivity. This study first investigated
      the hypothesis that ET-induced increases in net IMTG breakdown and insulin
      sensitivity are related to increased expression of perilipin 2 (PLIN2) and
      perilipin 5 (PLIN5). Second, we hypothesized that sprint interval training (SIT)
      also promotes increases in IMTG utilization and insulin sensitivity. Sixteen
      sedentary males performed 6 weeks of either SIT (4-6, 30 s Wingate tests per
      session, 3 days week(-1)) or ET (40-60 min moderate-intensity cycling, 5 days
      week(-1)). Training increased resting IMTG content (SIT 1.7-fold, ET 2.4-fold; P
      < 0.05), concomitant with parallel increases in PLIN2 (SIT 2.3-fold, ET 2.8-fold;
      P < 0.01) and PLIN5 expression (SIT 2.2-fold, ET 3.1-fold; P < 0.01). Pre
      training, 60 min cycling at ~65% pre-training decreased IMTG content in type I
      fibres (SIT 17 +/- 10%, ET 15 +/- 12%; P < 0.05). Following training, a
      significantly greater breakdown of IMTG in type I fibres occurred during exercise
      (SIT 27 +/- 13%, ET 43 +/- 6%; P < 0.05), with preferential breakdown of PLIN2-
      and particularly PLIN5-associated lipid droplets. Training increased the Matsuda
      insulin sensitivity index (SIT 56 +/- 15%, ET 29 +/- 12%; main effect P < 0.05).
      No training * group interactions were observed for any variables. In conclusion,
      SIT and ET both increase net IMTG breakdown during exercise and increase in PLIN2
      and PLIN5 protein expression. The data are consistent with the hypothesis that
      increases in PLIN2 and PLIN5 are related to the mechanisms that promote increased
      IMTG utilization during exercise and improve insulin sensitivity following 6
      weeks of SIT and ET.

PMID- 23129791
TI  - Expression of postsynaptic Ca2+-activated K+ (SK) channels at C-bouton synapses
      in mammalian lumbar -motoneurons.
AB  - Small-conductance calcium-activated potassium (SK) channels mediate medium after
      hyperpolarization (AHP) conductances in neurons throughout the central nervous
      system. However, the expression profile and subcellular localization of different
      SK channel isoforms in lumbar spinal alpha-motoneurons (alpha-MNs) is unknown.
      Using immunohistochemical labelling of rat, mouse and cat spinal cord, we reveal
      a differential and overlapping expression of SK2 and SK3 isoforms across specific
      types of alpha-MNs. In rodents, SK2 is expressed in all alpha-MNs, whereas SK3 is
      expressed preferentially in small-diameter alpha-MNs; in cats, SK3 is expressed
      in all alpha-MNs. Function-specific expression of SK3 was explored using post hoc
      immunostaining of electrophysiologically characterized rat alpha-MNs in vivo.
      These studies revealed strong relationships between SK3 expression and medium AHP
      properties. Motoneurons with SK3-immunoreactivity exhibit significantly longer
      AHP half-decay times (24.67 vs. 11.02 ms) and greater AHP amplitudes (3.27 vs.
      1.56 mV) than MNs lacking SK3-immunoreactivity. We conclude that the differential
      expression of SK isoforms in rat and mouse spinal cord may contribute to the
      range of medium AHP durations across specific MN functional types and may be a
      molecular factor distinguishing between slow- and fast-type alpha-MNs in rodents.
      Furthermore, our results show that SK2- and SK3-immunoreactivity is enriched in
      distinct postsynaptic domains that contain Kv2.1 channel clusters associated with
      cholinergic C-boutons on the soma and proximal dendrites of alpha-MNs. We suggest
      that this remarkably specific subcellular membrane localization of SK channels is
      likely to represent the basis for a cholinergic mechanism for effective
      regulation of channel function and cell excitability.

PMID- 23129792
TI  - N-terminal phosphorylation of cardiac troponin-I reduces length-dependent calcium
      sensitivity of contraction in cardiac muscle.
AB  - Protein kinase A (PKA) phosphorylation of myofibrillar proteins constitutes an
      important pathway for beta-adrenergic modulation of cardiac contractility. In
      myofilaments PKA targets troponin I (cTnI), myosin binding protein-C (cMyBP-C)
      and titin. We studied how this affects the sarcomere length (SL) dependence of
      force-pCa relations in demembranated cardiac muscle. To distinguish cTnI from
      cMyBP-C/titin phosphorylation effects on the force-pCa relationship, endogenous
      troponin (Tn) was exchanged in rat ventricular trabeculae with either wild-type
      (WT) Tn, non-phosphorylatable cTnI (S23/24A) Tn or phosphomimetic cTnI (S23/24D)
      Tn. PKA cannot phosphorylate either cTnI S23/24 variant, leaving cMyBP-C/titin as
      PKA targets. Force was measured at 2.3 and 2.0 MUm SL. Decreasing SL reduced
      maximal force (F(max)) and Ca(2+) sensitivity of force (pCa(50)) similarly with
      WT and S23/24A trabeculae. PKA treatment of WT and S23/24A trabeculae reduced
      pCa(50) at 2.3 but not at 2.0 MUm SL, thus eliminating the SL dependence of
      pCa(50). In contrast, S23/24D trabeculae reduced pCa(50) at both SL values,
      primarily at 2.3 MUm, also eliminating SL dependence of pCa(50). Subsequent PKA
      treatment moderately reduced pCa(50) at both SLs. At each SL, F(max) was
      unaffected by either Tn exchange and/or PKA treatment. Low-angle X-ray
      diffraction was performed to determine whether pCa(50) shifts were associated
      with changes in myofilament spacing (d(1,0)) or thick-thin filament interaction.
      PKA increased d(1,0) slightly under all conditions. The ratios of the integrated
      intensities of the equatorial X-ray reflections (I(1,1)/I(1,0)) indicate that PKA
      treatment increased crossbridge proximity to thin filaments under all conditions.
      The results suggest that phosphorylation by PKA of either cTnI or cMyBP-C/titin
      independently reduces the pCa(50) preferentially at long SL, possibly through
      reduced availability of thin filament binding sites (cTnI) or altered crossbridge
      recruitment (cMyBP-C/titin). Preferential reduction of pCa(50) at long SL may not
      reduce cardiac output during periods of high metabolic demand because of
      increased intracellular Ca(2+) during beta-adrenergic stimulation.

PMID- 23129794
TI  - The role of fructose transporters in diseases linked to excessive fructose
      intake.
AB  - Fructose intake has increased dramatically since humans were hunter-gatherers,
      probably outpacing the capacity of human evolution to make physiologically
      healthy adaptations. Epidemiological data indicate that this increasing trend
      continued until recently. Excessive intakes that chronically increase portal and
      peripheral blood fructose concentrations to >1 and 0.1 mm, respectively, are now
      associated with numerous diseases and syndromes. The role of the fructose
      transporters GLUT5 and GLUT2 in causing, contributing to or exacerbating these
      diseases is not well known. GLUT5 expression seems extremely low in neonatal
      intestines, and limited absorptive capacities for fructose may explain the high
      incidence of malabsorption in infants and cause problems in adults unable to
      upregulate GLUT5 levels to match fructose concentrations in the diet. GLUT5- and
      GLUT2-mediated fructose effects on intestinal electrolyte transporters, hepatic
      uric acid metabolism, as well as renal and cardiomyocyte function, may play a
      role in fructose-induced hypertension. Likewise, GLUT2 may contribute to the
      development of non-alcoholic fatty liver disease by facilitating the uptake of
      fructose. Finally, GLUT5 may play a role in the atypical growth of certain
      cancers and fat tissues. We also highlight research areas that should yield
      information needed to better understand the role of these GLUTs in fructose
      induced diseases.

PMID- 23129795
TI  - Descending control of the respiratory neuronal network by the midbrain
      periaqueductal grey in the rat in vivo.
AB  - Emotional reactions such as vocalization take place during expiration, and thus
      expression of emotional behaviour requires a switch from inspiration to
      expiration. I investigated how the midbrain periaqueductal grey (PAG), a known
      behavioural modulator of breathing, influences the inspiratory-to-expiratory
      phase transition. Contemporary models propose that late inspiratory (late-I) and
      post-inspiratory (post-I) neurones found in the medulla, which are active during
      the inspiratory-to-expiratory phase transition are involved in converting
      inspiration to expiration. I examined the effect of excitatory amino acid (d,l
      homocysteic acid; DLH) stimulation of the PAG on the discharge function of late-I
      and post-I neurones. The data show a topographical organization of DLH-induced
      late-I and post-I neuronal modulation within the PAG. Dorsal PAG stimulation
      induced tachypnoea and caused excitation of both the late-I and post-I neurones.
      Lateral PAG induced inspiratory prolongation and caused an excitation of late-I
      neurones but inhibition of post-I neurones. Ventrolateral PAG induced expiratory
      prolongation and caused a persistent activation of post-I neurones. As well, PAG
      stimulation modulated both the late-I and post-I cells for least two-three
      breaths even prior to the change in respiratory motor pattern. This indicates
      that the PAG influences the late-I and post-I cells independent of pulmonary or
      other sensory afferent feedback. I conclude that the PAG modulates the activity
      of the medullary late-I and post-I neurones, and this modulation contributes to
      the conversion of eupnoea into a behavioural breathing pattern.

PMID- 23129797
TI  - Generation of striatal projection neurons extends into the neonatal period in the
      rat brain.
AB  - Substantial advances have been made in the last decade on our understanding of
      the basic physiology underlying neurogenesis in the postnatal mammalian brain.
      The bulk of the work in this area has been based on analysis of the adult brain.
      Relatively less is known about the capacity for neurogenesis in specific
      structures within the neonatal brain. Here we report that the production of
      medium spiny striatal projection neurons extends into the early neonatal period
      under normal physiological conditions in the rat brain. Birth-dating of newborn
      cells with bromodeoxyuridine at postnatal days 0, 2 and 5 showed a peak
      production close to birth, which sharply declined at the later time-points.
      Additionally, there was a low-level but stable contribution of neurons with
      interneuron identity over the same time-period. Importantly, retroviral labelling
      of new striatal projection neurons with green fluorescent protein showed long
      term survival and terminal differentiation with characteristic morphology,
      including highly elaborated spiny dendrites, and appropriate axonal targeting of
      the globus pallidus and midbrain. This latent period of striatal neurogenesis in
      the early neonatal brain represents an interesting target for regenerative
      approaches aimed at restoring striatal circuitry in perinatal pathologies, such
      as hypoxic and ischaemic damage associated with cerebral palsy.

PMID- 23129799
TI  - Bronchiectasis: time to take action and implement the British Thoracic Society
      quality standards.

PMID- 23129796
TI  - Disturbed energy metabolism and muscular dystrophy caused by pure creatine
      deficiency are reversible by creatine intake.
AB  - Creatine (Cr) plays an important role in muscle energy homeostasis by its
      participation in the ATP-phosphocreatine phosphoryl exchange reaction mediated by
      creatine kinase. Given that the consequences of Cr depletion are incompletely
      understood, we assessed the morphological, metabolic and functional consequences
      of systemic depletion on skeletal muscle in a mouse model with deficiency of l
      arginine:glycine amidinotransferase (AGAT(-/-)), which catalyses the first step
      of Cr biosynthesis. In vivo magnetic resonance spectroscopy showed a near
      complete absence of Cr and phosphocreatine in resting hindlimb muscle of AGAT(-/
      ) mice. Compared with wild-type, the inorganic phosphate/beta-ATP ratio was
      increased fourfold, while ATP levels were reduced by nearly half. Activities of
      proton-pumping respiratory chain enzymes were reduced, whereas F(1)F(0)-ATPase
      activity and overall mitochondrial content were increased. The Cr-deficient AGAT(
      /-) mice had a reduced grip strength and suffered from severe muscle atrophy.
      Electron microscopy revealed increased amounts of intramyocellular lipid droplets
      and crystal formation within mitochondria of AGAT(-/-) muscle fibres. Ischaemia
      resulted in exacerbation of the decrease of pH and increased glycolytic ATP
      synthesis. Oral Cr administration led to rapid accumulation in skeletal muscle
      (faster than in brain) and reversed all the muscle abnormalities, revealing that
      the condition of the AGAT(-/-) mice can be switched between Cr deficient and
      normal simply by dietary manipulation. Systemic creatine depletion results in
      mitochondrial dysfunction and intracellular energy deficiency, as well as
      structural and physiological abnormalities. The consequences of AGAT deficiency
      are more pronounced than those of muscle-specific creatine kinase deficiency,
      which suggests a multifaceted involvement of creatine in muscle energy
      homeostasis in addition to its role in the phosphocreatine-creatine kinase
      system.

PMID- 23129798
TI  - Late-onset bursts evoked by mossy fibre bundle stimulation in unipolar brush
      cells: evidence for the involvement of H- and TRP-currents.
AB  - Synaptic transmission at central synapses has usually short latency and graded
      amplitude, thereby regulating threshold crossing and the probability of action
      potential generation. In the granular layer of the vestibulo-cerebellum, unipolar
      brush cells (UBCs) receive a giant synapse generating a stereotyped excitatory
      postsynaptic potential (EPSP)-burst complex with early-onset (~2 ms) and high
      reliability. By using patch-clamp recordings in cerebellar slices of the rat
      vestibulo-cerebellum, we found that mossy fibre bundle stimulation also evoked
      (in ~80% of cases) a late-onset burst (after tens to hundreds of milliseconds)
      independent of EPSP generation. Different from the early-onset, the late-onset
      burst delay decreased and its duration increased by raising stimulation intensity
      or the number of impulses. Although depending on synaptic activity, the late
      onset response was insensitive to perfusion of APV ((2R)-5-amino
      phosphonopentanoate), NBQX (2,3-dioxo-6-nitro-tetrahydrobenzo(f)quinoxaline-7
      sulfonamide) and MCPG ((RS)-alpha-methyl-4-carboxyphenylglycine) and did not
      therefore depend on conventional glutamatergic transmission mechanisms. The late
      onset response was initiated by a slow depolarizing ramp driven by activation of
      an H-current (sensitive to ZD7288 and Cs(+)) and of a TRP- (transient receptor
      potential) current (sensitive to SKF96365), while the high voltage-activated and
      high voltage-activated Ca(2+) currents (sensitive to nimodipine and mibefradil,
      respectively) played a negligible role. The late-onset burst was occluded by
      intracellular cAMP. These results indicate that afferent activity can regulate H-
      and TRP-current gating in UBCs generating synaptically driven EPSP-independent
      responses, in which the delay rather than amplitude is graded with the intensity
      of the input pattern. This modality of synaptic transmission may play an
      important role in regulating UBC activation and granular layer functions in the
      vestibulo-cerebellum.

PMID- 23129800
TI  - Systemic comorbidities in bronchiectasis.
AB  - Bronchiectasis is a chronic inflammatory lung disease, which has similarities to
      chronic obstructive pulmonary disease (COPD). Comorbidities of COPD include
      increased risk of cardiovascular (CV) disease, loss of bone mineral density (BMD)
      and loss of skeletal muscle mass and function, all linked to systemic
      inflammation. The potential for such comorbidities has not been explored in
      bronchiectasis. We hypothesised that patients with bronchiectasis would have
      similar increased comorbidities. A total of 20 patients with noncystic fibrosis
      bronchiectasis were compared to 20 controls similar in age, gender and smoking
      exposure. Assessments included aortic pulse wave velocity (PWV; (a measure of
      arterial stiffness and an independent predictor of CV risk), blood pressure (BP)
      as well as levels of interleukin-6 (IL-6), albumin, fasting glucose and lipids.
      Body composition (fat free mass index (FFMI)), BMD, the 6-min walk distance
      (6MWD) and self-reported physical activity were also determined. Patients with
      bronchiectasis had increased aortic PWV, 10.5 (3.0) m/second, when compared with
      controls, 8.8 (1.6) m/second (p < 0.05), despite similar central and peripheral
      BP and lipid profile. Patients also had increased IL-6 and reduced albumin and
      glucose. Although mean body mass index, FFMI and BMD were similar in patients and
      controls, only 20% of patients had a healthy BMD compared with 50% of controls.
      Patients had reduced 6MWD and reported less physical activity (p < 0.05).
      Patients with bronchiectasis had increased arterial stiffness (an indicator of
      increased CV risk), increased inflammation, reduced exercise capacity and bone
      thinning. These additional comorbidities require further evaluation for their
      management in these patients.

PMID- 23129801
TI  - Maximum voluntary ventilation is more strongly associated with energy expenditure
      during simple activities of daily living than measures of airflow obstruction or
      respiratory muscle strength in patients with COPD.
AB  - This is a retrospective analysis of data in which we explored the association
      between energy expenditure (EE) and lung function in patients with chronic
      obstructive pulmonary disease (COPD). A total of 36 participants (20 males;
      forced expiratory volume in 1 second (FEV(1)) of 48 +/- 15% predicted) underwent
      measures of indirect calorimetry whilst performing five simple activities of
      daily living. Maximal voluntary ventilation was the only lung function parameter
      associated with EE. These data highlight the limited extent to which the FEV(1)
      is related to the functional performance of patients with COPD.

PMID- 23129802
TI  - Fatigue in cystic fibrosis: a novel prospective study investigating subjective
      and objective factors associated with fatigue.
AB  - Fatigue is a debilitating symptom in patients with cystic fibrosis (CF). Although
      fatigue is commonly reported in these patients, an effective treatment for this
      symptom has not been found. The factors associated with fatigue in CF have not
      been investigated. We conducted a prospective, case-control study in adult
      patients with CF. All the patients were chronically infected with Pseudomonas
      aeruginosa and were enrolled in the study during disease stability. A gender and
      age-matched control group was also recruited. Subjective assessment included
      three questionnaires: the Chalder fatigue questionnaire, St Mary's Hospital sleep
      questionnaire (SQ), and the scaled general health and Hillier questionnaire
      (GHQ). For patients with CF, spirometry, body mass index (BMI), haemoglobin
      level, C-reactive protein, and the burden of pulmonary exacerbations (PExs) were
      assessed. The control group completed all the three questionnaires, and their BMI
      was measured. A total of 78 participants were enrolled in the study (44 patients
      with CF and 34 control). Female patients with CF received antibiotics for more
      days than male patients with CF. The fatigue score did not differ between female
      and male participants in either the patients with CF or the control group;
      however, the fatigue score was greater for both the sexes in the patients with CF
      compared with the control group: p = 0.038 for female and p = 0.048 for male. The
      scores for the SQ and the GHQ did not differ between the two study groups. The
      fatigue score correlated with the total score for SQ (p < 0.0001) in patients
      with CF, but not in control participants. In patients with CF and the individuals
      in the control group, a close correlation was found between the fatigue score and
      the GHQ domain-specific scores and with the total score; p < 0.0001 for patients
      with CF and p = 0.001 for control. No correlations were found between the fatigue
      score and any of the objective parameters studied.

PMID- 23129803
TI  - Collaborative self-management in chronic obstructive pulmonary disease: learning
      ways to promote patient motivation and behavioral change.

PMID- 23129804
TI  - A simple method to enable patient-tailored treatment and to motivate the patient
      to change behaviour.
AB  - In clinical practice and in self-management studies it appears that it is very
      difficult to change behaviour in patients with chronic obstructive pulmonary
      disease (COPD) in order to achieve adequate self-management. In this respect the
      role of motivational processes is underestimated and rarely is specifically
      targeted in interventions. In this article, the fundamentals of motivational
      processes are discussed followed by a detailed description of the Nijmegen
      Clinical Screening Instrument (NCSI) method. The NCSI method is a simple method
      that enables patient-tailored treatment and to motivate patients to adhere to
      treatment goals. The NCSI method consists of three distinct but highly integrated
      components: (1) a short instrument measuring many details of health status; (2)
      an intervention that helps to identify individual treatment goals and to motivate
      the patient to change his behaviour; (3) an automated monitoring system that
      simply identifies patients with new problems in health status of self-management.
      All components are embedded in a web-based application which enhances simplicity,
      efficiency, and effectiveness of the NCSI method. The NCSI method is illustrated
      by a case study.

PMID- 23129805
TI  - Fendiline inhibits K-Ras plasma membrane localization and blocks K-Ras signal
      transmission.
AB  - Ras proteins regulate signaling pathways important for cell growth,
      differentiation, and survival. Oncogenic mutant Ras proteins are commonly
      expressed in human tumors, with mutations of the K-Ras isoform being most
      prevalent. To be active, K-Ras must undergo posttranslational processing and
      associate with the plasma membrane. We therefore devised a high-content screening
      assay to search for inhibitors of K-Ras plasma membrane association. Using this
      assay, we identified fendiline, an L-type calcium channel blocker, as a specific
      inhibitor of K-Ras plasma membrane targeting with no detectable effect on the
      localization of H- and N-Ras. Other classes of L-type calcium channel blockers
      did not mislocalize K-Ras, suggesting a mechanism that is unrelated to calcium
      channel blockade. Fendiline did not inhibit K-Ras posttranslational processing
      but significantly reduced nanoclustering of K-Ras and redistributed K-Ras from
      the plasma membrane to the endoplasmic reticulum (ER), Golgi apparatus,
      endosomes, and cytosol. Fendiline significantly inhibited signaling downstream of
      constitutively active K-Ras and endogenous K-Ras signaling in cells transformed
      by oncogenic H-Ras. Consistent with these effects, fendiline blocked the
      proliferation of pancreatic, colon, lung, and endometrial cancer cell lines
      expressing oncogenic mutant K-Ras. Taken together, these results suggest that
      inhibitors of K-Ras plasma membrane localization may have utility as novel K-Ras
      specific anticancer therapeutics.

PMID- 23129806
TI  - Fat body dSir2 regulates muscle mitochondrial physiology and energy homeostasis
      nonautonomously and mimics the autonomous functions of dSir2 in muscles.
AB  - Sir2 is an evolutionarily conserved NAD(+)-dependent deacetylase which has been
      shown to play a critical role in glucose and fat metabolism. In this study, we
      have perturbed Drosophila Sir2 (dSir2) expression, bidirectionally, in muscles
      and the fat body. We report that dSir2 plays a critical role in insulin
      signaling, glucose homeostasis, and mitochondrial functions. Importantly, we
      establish the nonautonomous functions of fat body dSir2 in regulating
      mitochondrial physiology and insulin signaling in muscles. We have identified a
      novel interplay between dSir2 and dFOXO at an organismal level, which involves
      Drosophila insulin-like peptide (dILP)-dependent insulin signaling. By genetic
      perturbations and metabolic rescue, we provide evidence to illustrate that fat
      body dSir2 mediates its effects on the muscles via free fatty acids (FFA) and
      dILPs (from the insulin-producing cells [IPCs]). In summary, we show that fat
      body dSir2 is a master regulator of organismal energy homeostasis and is required
      for maintaining the metabolic regulatory network across tissues.

PMID- 23129807
TI  - RBM4 promotes pancreas cell differentiation and insulin expression.
AB  - The RNA-binding protein RNA-binding motif protein 4 (RBM4) modulates alternative
      splicing of muscle-specific mRNA isoforms during muscle cell differentiation. To
      better understand the physiological function of RBM4, we exploited a gene
      knockout strategy in the present study. Mice with targeted disruption of one of
      the two Rbm4 genes exhibited hyperglycemia coincident with reduced levels of
      serum insulin and reduced size of pancreatic islets. The embryonic pancreases of
      Rbm4-deficient mice showed reduced expression or aberrant splicing of many
      transcripts encoding factors required for pancreas cell differentiation and
      function. Using pancreatic acinar AR42J cells, we demonstrated that RBM4 promoted
      insulin gene expression by altering the isoform balance of the transcription
      factors Isl1 and Pax4 via alternative splicing control. RBM4 overexpression was
      sufficient to convert AR42J cells into insulin-producing cells. Moreover, RBM4
      may mediate glucose-induced insulin expression and insulin receptor isoform
      switches. These results suggest that RBM4 may have role in promoting pancreas
      cell differentiation and endocrine function, essentially via alternative splicing
      regulation.

PMID- 23129808
TI  - Novel role for SHP-2 in nutrient-responsive control of S6 kinase 1 signaling.
AB  - Amino acids are required for the activation of the mammalian target of rapamycin
      complex 1 (mTORC1), which plays a critical role in cell growth, proliferation,
      and metabolism. The branched-chain amino acid leucine is an essential nutrient
      that stimulates mTORC1 to promote protein synthesis by activating p70 S6 kinase 1
      (S6K1). Here we show that the protein tyrosine phosphatase SHP-2 is required for
      leucine-induced activation of S6K1 in skeletal myoblasts. In response to leucine,
      S6K1 activation is inhibited in myoblasts either lacking SHP-2 expression or
      overexpressing a catalytically inactive mutant of SHP-2. Activation of S6K1 by
      leucine requires the mobilization of intracellular calcium (Ca(2+)), which we
      show is mediated by SHP-2 in an inositol-1,4,5-trisphosphate-dependent manner.
      Ectopic Ca(2+) mobilization rescued the S6K1 activation defect in SHP-2-deficient
      myoblasts. SHP-2 was identified to act upstream of phospholipase C beta4, linking
      it to the generation of nutrient-induced Ca(2+) release and S6K1 phosphorylation.
      Consistent with these results, SHP-2-deficient myoblasts exhibited impaired
      leucine sensing, leading to defective autophagy and reduced myoblast size. These
      data define a new role for SHP-2 as a nutrient-sensing regulator in skeletal
      myoblasts that is required for the activation of S6K1.

PMID- 23129809
TI  - ARID1a-DNA interactions are required for promoter occupancy by SWI/SNF.
AB  - Every known SWI/SNF chromatin-remodeling complex incorporates an ARID DNA binding
      domain-containing subunit. Despite being a ubiquitous component of the complex,
      physiological roles for this domain remain undefined. Here, we show that
      disruption of ARID1a-DNA binding in mice results in embryonic lethality, with
      mutant embryos manifesting prominent defects in the heart and extraembryonic
      vasculature. The DNA binding-defective mutant ARID1a subunit is stably expressed
      and capable of assembling into a SWI/SNF complex with core catalytic properties,
      but nucleosome substrate binding and promoter occupancy by ARID1a-containing
      SWI/SNF complexes (BAF-A) are impaired. Depletion of ARID domain-dependent, BAF-A
      associations at THROMBOSPONDIN 1 (THBS1) led to the concomitant upregulation of
      this SWI/SNF target gene. Using a THBS1 promoter-reporter gene, we further show
      that BAF-A directly regulates THBS1 promoter activity in an ARID domain-dependent
      manner. Our data not only demonstrate that ARID1a-DNA interactions are
      physiologically relevant in higher eukaryotes but also indicate that these
      interactions facilitate SWI/SNF binding to target sites in vivo. These findings
      support the model wherein cooperative interactions among intrinsic subunit
      chromatin interaction domains and sequence-specific transcription factors drive
      SWI/SNF recruitment.

PMID- 23129810
TI  - Intestinal master transcription factor CDX2 controls chromatin access for partner
      transcription factor binding.
AB  - Tissue-specific gene expression requires modulation of nucleosomes, allowing
      transcription factors to occupy cis elements that are accessible only in selected
      tissues. Master transcription factors control cell-specific genes and define
      cellular identities, but it is unclear if they possess special abilities to
      regulate cell-specific chromatin and if such abilities might underlie lineage
      determination and maintenance. One prevailing view is that several transcription
      factors enable chromatin access in combination. The homeodomain protein CDX2
      specifies the embryonic intestinal epithelium, through unknown mechanisms, and
      partners with transcription factors such as HNF4A in the adult intestine. We
      examined enhancer chromatin and gene expression following Cdx2 or Hnf4a excision
      in mouse intestines. HNF4A loss did not affect CDX2 binding or chromatin, whereas
      CDX2 depletion modified chromatin significantly at CDX2-bound enhancers,
      disrupted HNF4A occupancy, and abrogated expression of neighboring genes. Thus,
      CDX2 maintains transcription-permissive chromatin, illustrating a powerful and
      dominant effect on enhancer configuration in an adult tissue. Similar,
      hierarchical control of cell-specific chromatin states is probably a general
      property of master transcription factors.

PMID- 23129812
TI  - Short-term effects of spinal thrust joint manipulation in patients with chronic
      neck pain: a randomized clinical trial.
AB  - OBJECTIVE: To compare the effects of an isolated application of cervical spine
      thrust joint manipulation vs. the application of cervical, cervico-thoracic
      junction and thoracic manipulation on neck pain, disability and cervical range of
      motion in chronic neck pain. DESIGN: Randomized clinical trial. SETTING: Clinical
      practice. PARTICIPANTS: Eighty-two patients (41 females) with chronic mechanical
      neck pain. INTERVENTIONS: Patients were randomly assigned to a cervical spine
      manipulation group or a full manipulative group who received mid-cervical,
      cervico-thoracic and thoracic joint manipulations. MEASUREMENTS: Neck pain
      intensity (11-point numeric pain rating scale), self-reported disability (Neck
      Disability Index) and cervical range of motion were collected at baseline and one
      week after the intervention by an assessor blinded to the allocation of the
      patients. RESULTS: A significant Group * Time interaction for Neck Disability
      Index (P = 0.022), but not for neck pain (P = 0.612), was found: patients in the
      full manipulative group exhibited greater reduction in disability than those who
      received the cervical spine manipulation alone, whereas both groups experienced
      similar decreases in neck pain. Patients in both groups experienced similar
      increases in cervical range of motion (P > 0.4). No effect of gender was observed
      (P > 0.299). CONCLUSIONS: In patients with chronic mechanical neck pain,
      manipulation of the cervical and thoracic spine leads to a greater reduction in
      disability at one week than after manipulation of the cervical spine alone,
      whereas changes in pain and range of motion are not affected differently.

PMID- 23129811
TI  - Nucleotide composition of cellular internal ribosome entry sites defines
      dependence on NF45 and predicts a posttranscriptional mitotic regulon.
AB  - The vast majority of cellular mRNAs initiate their translations through a well
      defined mechanism of ribosome recruitment that occurs at the 5'-terminal 7
      methylguanosine cap with the help of several canonical protein factors. A subset
      of cellular and viral mRNAs contain regulatory motifs in their 5' untranslated
      regions (UTRs), termed internal ribosome entry sites (IRES), that sidestep this
      canonical mode of initiation. On cellular mRNAs, this mechanism requires IRES
      trans-acting protein factors (ITAFs) that facilitate ribosome recruitment
      downstream of the cap. While several ITAFs and their target mRNAs have been
      empirically identified, the in silico prediction of targets has proved difficult.
      Here, we report that a high AU content (>60%) of the IRES-containing 5' UTRs
      serves as an excellent predictor of dependence on NF45, a recently identified
      ITAF. Moreover, we provide evidence that cells deficient in NF45 ITAF activity
      exhibit reduced IRES-mediated translation of X-linked inhibitor of apoptosis
      protein (XIAP) and cellular inhibitor of apoptosis protein 1 (cIAP1) mRNAs that,
      in turn, leads to dysregulated expression of their respective targets, survivin
      and cyclin E. This specific defect in IRES translation explains in part the
      cytokinesis impairment and senescence-like phenotype observed in HeLa cells
      expressing NF45 RNA interference (RNAi). This study uncovers a novel role for
      NF45 in regulating ploidy and highlights the importance of IRES-mediated
      translation in cellular homeostasis.

PMID- 23129813
TI  - Long-term benefits of the Memory-Link programme in a case of amnesia.
AB  - OBJECTIVE: To systematically evaluate the maintenance of clinical gains from a
      structured memory intervention programme. Efficacy of the programme was initially
      demonstrated in RR, a woman with moderate-to-severe memory impairment following
      colloid cyst removal. In the current study (Svoboda and Richards, 2009), we
      examined RR's day-to-day memory functioning 18 months after completion of the
      intervention programme. DESIGN: Within-subject A(1)B(1)A(2)B(2)B(3) single-case
      experimental design. SETTING: Outpatient memory rehabilitation clinic.
      INTERVENTION: A theory-driven training programme in the use of commercially
      available smartphones for individuals with moderate-to-severe memory impairment.
      MAIN MEASURES: A phone call task was used as an objective measure of prospective
      memory function. Self-report, ecologically valid questionnaires were also
      completed to further assess generalization of smartphone use to day-to-day memory
      function. RESULTS: Eighteen months after intervention, RR completed 80% of
      scheduled calls using the smartphone, a rate significantly higher than at
      baseline (40%) and comparable to her success rate immediately following
      intervention (90%) and at the four-month follow-up (90%). Responses to
      questionnaires indicated that RR felt more confident in her ability to handle
      memory-demanding situations and was making fewer memory mistakes. This favourable
      outcome was not found with the use of another smartphone brand for which training
      was not received. CONCLUSIONS: Results from ecologically valid measures of memory
      functioning demonstrated robust maintenance of independent commercial smartphone
      use over an 18-month period, with increases observed in independence, confidence
      and real-life memory functioning. The findings further suggest poor cross-device
      generalizability.

PMID- 23129815
TI  - Effects of motor imagery training on balance and gait abilities in post-stroke
      patients: a randomized controlled trial.
AB  - OBJECTIVES: To investigate the effects of motor imagery training on the balance
      and gait abilities of post-stroke patients. DESIGN: Randomized controlled trial.
      SETTING: Outpatient rehabilitation centre. SUBJECTS: Twenty-eight individuals
      with chronic stroke. INTERVENTIONS: The experimental group (n = 15) performed
      motor imagery training involving imagining normal gait movement for 15 minutes
      embedded in gait training for 30 minutes (45 minutes/day, 3 times/week); the
      control group (n = 13) performed gait training only (30 minutes/day, 3
      times/week). MAIN MEASURES: Balance and gait abilities were measured by the
      Functional Reach Test, Timed Up-and-Go Test, 10-m Walk Test and Fugl-Meyer
      assessment before and after interventions. RESULTS: All measurements improved
      significantly compared with baseline values in the experimental group. In the
      control group, there were significant improvements in all parameters except the
      Fugl-Meyer assessment. All parameters of the experimental group increased
      significantly compared to those of the control group as follows: Functional Reach
      Test (control vs. experimental: 28.1 +/- 3.1 vs. 37.51 +/- 3.0), Timed Up-and-Go
      Test (20.7 +/- 4.0 vs. 13.2 +/- 2.2), 10-m Walk Test (17.4 +/- 4.6 vs. 16.0 +/-
      2.7) and Fugl-Meyer assessment (12.0 +/- 2.9 vs. 17.6 +/- 1.3). CONCLUSIONS: Gait
      training with motor imagery training improves the balance and gait abilities of
      chronic stroke patients significantly better than gait training alone.

PMID- 23129814
TI  - A randomized controlled trial of surface neuromuscular electrical stimulation
      applied early after acute stroke: effects on wrist pain, spasticity and
      contractures.
AB  - OBJECTIVES: To investigate effects of surface neuromuscular electrical
      stimulation applied early after stroke to the wrist and finger extensor muscles
      on upper limb pain, spasticity and contractures in patients with no functional
      arm movement. DESIGN: Secondary analysis from a Phase II, randomized, controlled,
      single-blind study. SETTING: An acute hospital stroke unit. SUBJECTS: Patients
      with no useful arm function within six weeks of a first stroke. INTERVENTION:
      Patients were randomized to treatment (30-minute sessions of surface
      neuromuscular stimulation to wrist and finger extensors and 45 minutes of
      physiotherapy) or control (45 minutes of physiotherapy) groups. All patients had
      access to routine care. Treatment was given for six weeks from recruitment.
      RESULTS: Ninety patients (49% male, median age 74 years (range 32-98), median
      time since stroke onset three weeks (range one to six weeks)) were included.
      Treatment compliance was variable (mean 28%). The treatment prevented the
      development of pain (mean difference in rate of change 0.4 units/week, 95%
      confidence interval (CI) 0.09 to 0.6). Treatment may have prevented a
      deterioration in contractures (quantified by measuring passive range of movement)
      in severely disabled patients (mean rate of deterioration -0.5 deg/week; 95% CI 
      0.9 to -0.06). There were no significant changes in stiffness and spasticity.
      CONCLUSION: Surface neuromuscular electrical stimulation reduces pain in stroke
      patients with a non-functional arm. There was some evidence that treatment with
      electrical stimulation was beneficial in reducing contractures. Treatment had no
      effect on spasticity.

PMID- 23129816
TI  - Organ markets and harms: a reply to Dworkin, Radcliffe Richards and Walsh.

PMID- 23129817
TI  - The perils of post-persons.

PMID- 23129818
TI  - The minimally conscious state and treatment withdrawal: W v M.
AB  - This short comment on the Court of Protection decision in W v M draws attention
      to the primacy the judge gave to the preservation of life and discusses the
      relative lack of weight accorded to M's previously expressed views. 

PMID- 23129819
TI  - Perpetual bodily trauma: wounding and memory in the Middle English romances.
AB  - In the 21st century, the concept of trauma is deeply ingrained in psychological
      discourse despite the term's origins in literal, physical wounding and affecting
      experience. However, to understand the sources or causes of trauma, psychologists
      recognise the paramount importance of somatic evidence. The body provides
      corporeal systems for inputs that might trigger a later remembrance which might
      be auditory, visual, even tactile. The same body will continue to experience the
      trauma throughout its life, only alleviated, perhaps, by an appropriate
      therapeutic or chemical treatment. The body is therefore an important source of
      the trauma as an affected entity inscribed with experience, but the corporeal
      form also offers a way in which to identify and understand traumatic suffering
      itself. In the medieval period, trauma or violent experiences were similarly
      viewed as corporeal inscriptions which may fade but, metaphorically, remain
      immediately wounding. This paper explores the presentation of trauma in medieval
      romances, narratives strewn with injured bodies and correspondingly altered
      personalities and reputations, and compares this with contemporary research
      relating to trauma and the neurobiology of consciousness. The core issue is one
      of experience and expression: how an individual feels and continues to suffer
      trauma, and the ways in which that suffering can be communicated to those around.
      Through considering this issue, the paper argues for a relationship between the
      human experience of trauma across the centuries, and with this the combination of
      corporeal symbol and affect, and the dynamic interaction of a wounded body with
      time and its later life.

PMID- 23129820
TI  - Chronic renal impairment and DDAH2-1151 A/C polymorphism determine ADMA levels in
      type 2 diabetic subjects.
AB  - BACKGROUND: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of
      nitric oxide synthase (NOS). Increased levels of ADMA cause impaired
      vasodilation, leading to endothelial dysfunction and a higher risk for
      cardiovascular events. In patients with a chronic kidney disease, increased ADMA
      levels are reported to play a role in the pathogenesis of accelerated
      atherosclerosis and are an independent risk marker leading to end-stage renal
      disease and mortality. Circulating ADMA is metabolized by the action of
      dimethylarginine dimethylamino hydrolase (DDAH) and DDAH2 isoform is the most
      prevalent in tissues expressing endothelial NOS. DDAH and NOS are co-expressed in
      the same kidney regional sites supporting the hypothesis that a strict and
      specific regulation of intracellular ADMA levels is crucial for NO generation in
      the kidney. Starting from these findings, the study aims to investigate the role
      of DDAH2 gene promoter polymorphism at position -1151 A/C in determining the
      levels of ADMA in type 2 diabetic patients (T2DM) with chronic renal impairment.
      METHODS: Three groups of carefully selected subjects of both sexes were enrolled
      and compared. The first group (control subjects) comprised 286 non-diabetic
      subjects (mean age 55.8 +/- 11.4 years), the second group (T2DM uncomplicated
      subjects) was made up of 322 T2DM subjects without complications (mean age 64.9
      +/- 9.6 years) whereas the third group (T2DM CRF subjects) included 110 T2DM
      patients with chronic renal impairment. The rs805304 DDAH2-1151 A/C promoter
      polymorphism was determined by a polymerase chain reaction-restriction fragment
      length polymorphism approach. Results T2DM CRF subjects showed significant
      increased plasma levels of ADMA with respect to those of T2DM uncomplicated
      subjects and control subjects (0.51 versus 0.39 versus 0.37 MUmol/L, P = 0.002,
      respectively). Analysis of variance showed an interaction between DDAH2-1151 C
      carrier and groups on ADMA plasma levels (F = 4.36; P < 0.05). ADMA plasma levels
      were also dependent on groups (F = 4.96; P < 0.01). CONCLUSIONS: Our work
      demonstrates that rs805304 DDAH2-1151 polymorphism plays a central role in
      determining ADMA in diabetic renal impairment, where patients with DDAH2-1151 C
      carriers showed the highest ADMA levels. This unfavourable genetic profile is
      highlighted by pathological kidney conditions such as diabetic CRF. These
      findings could open new insights on the pathways involving ADMA/DDAH/NOS in the
      development and progression of chronic renal impairment and therefore of the
      other micro- macrovascular diabetic complications.

PMID- 23129821
TI  - The relevance of dietary sodium in hemodialysis.
AB  - Since the earliest days of hemodialysis, dietary sodium restriction has been
      recommended as a therapeutic means to mitigate problems of extracellular volume
      overload, hypertension and inter-dialytic weight gain. Recently, there has been a
      proliferation of human subjects' research examining the potential effects of
      dietary sodium curtailment. Herein we examine the available evidence with respect
      to the effects of dietary sodium restriction on clinically relevant endpoints
      among hemodialysis patients.

PMID- 23129822
TI  - Acute and chronic effects of dietary sodium restriction on renal
      tubulointerstitial fibrosis in cisplatin-treated rats.
AB  - BACKGROUND: Renal interstitial fibrosis is a major complication of cisplatin (CP)
      treatment, and increased sodium intake may accelerate its progression by
      stimulating transforming growth factor (TGF)-beta/Smad signaling. However, it is
      not clear whether a low-sodium diet has beneficial effects on the development of
      interstitial fibrosis because it activates the renin-angiotensin-aldosterone
      system. Here, we tested whether the TGF-beta/Smad signaling pathway is stimulated
      in CP-treated rats, and whether the development of tubulointerstitial fibrosis in
      CP nephropathy can be checked by dietary sodium restriction. METHODS: Male
      Sprague Dawley rats were randomly divided into controls, CP treatment and CP
      treatment with low-sodium diet. The acute experiment lasted 7 days with a single
      intraperitoneal injection (6 mg/kg) of CP, and the chronic experiment involved
      weekly injections (2 mg/kg) for 7 weeks. RESULTS: In both sets of experiments, CP
      treatment produced pronounced tubulointerstitial injury, increased infiltration
      of ED1-positive cells and increased expression of monocyte chemotactic protein-1
      (MCP-1), alpha-smooth muscle actin (SMA), TGF-beta1, phosphorylated Smad3,
      fibronectin and collagen III proteins. In the acute experiment, the increases in
      expression of osteopontin, MCP-1, alpha-SMA, TGF-beta and collagen III were
      significantly reduced by dietary sodium restriction. In the chronic experiment,
      however, none of the measurements were improved by a low-sodium diet. Examination
      of CP-treated rat kidneys revealed de novo vimentin expression in tubular
      epithelial cells and invasion of alpha-SMA-positive tubular epithelial cells
      through the basement membrane into the interstitium. CONCLUSIONS: The pro
      fibrotic effect of TGF-beta in CP nephropathy appears to be associated with the
      epithelial-mesenchymal transition and is ameliorated by dietary sodium
      restriction only during the acute phase.

PMID- 23129823
TI  - A randomized controlled trial of exercise training on cardiovascular and
      autonomic function among renal transplant recipients.
AB  - BACKGROUND: There are conflicting data regarding the effects of renal
      transplantation (RT) on uraemic autonomic dysfunction. Moreover, no study has
      examined the impact of physical training on the cardiac autonomic function in RT
      patients. Thus, we studied the effects of exercise training on heart rate
      variability (HRV) and arterial baroreflex sensitivity (BRS), which are sensitive
      markers of cardiac autonomic outflow, in RT recipients. METHODS: Eleven patients
      (Exercise group-aged 52.1 +/- 5.6 years) were studied before and after 6 months
      of exercise training. Twelve age- and sex- matched RT patients (Sedentary) and 12
      healthy sedentary individuals (Healthy), who remained untrained, served as
      controls. At baseline and follow-up, all the subjects underwent cardiopulmonary
      exercise testing for the evaluation of peak oxygen consumption (VO2peak), a tilt
      test for the evaluation of BRS and baroreflex effectiveness index (BEI) and an
      ambulatory 24-h Holter monitoring for time- and frequency-domain measures of HRV.
      RESULTS: In the exercise group, VO2peak increased by 15.8% (P < 0.05) and all
      depressed HRV and BRS indices were significantly improved after training.
      Specifically, the standard deviation of all normal-to-normal (NN) intervals
      (SDNN) significantly increased by 92.5%, the root-mean-square of the differences
      between consecutive NN intervals by 45.4%, the percentage value of NN50 count by
      58.2%, the high-frequency by 74.8% and low-frequency spectral power by 41.6%, BRS
      by 43.7% and BEI by 57.3%. None of the variables studied was altered over time in
      either control group. CONCLUSIONS: The increased cardiorespiratory fitness by
      exercise training was associated with an improved BRS function and a modification
      of the sympathovagal control of HRV towards a persistent increase in
      parasympathetic tone. These alterations may lead to a better cardiovascular
      prognosis in RT recipients.

PMID- 23129824
TI  - Late-onset post-transplantation lymphoproliferative disorders after kidney
      transplantation: a monocentric study over three decades.
AB  - BACKGROUND: Late-onset post-transplantation lymphoproliferative disorders (PTLDs)
      occur 1 year after transplantation and are associated with poor prognosis.
      Initial treatment usually involves a reduction in immunosuppressive treatment.
      While early-onset PTLDs have a good prognosis following RI, this approach is
      generally inadequate for late-onset PTLDs. We assessed the specific outcome of
      late-onset PTLDs after kidney transplantation during the past three decades.
      METHODS: We reviewed the clinical and biological data of 52 kidney transplant
      recipients who developed late-onset PTLDs at our centre between 1980 and 2010. We
      compared clinical features, long-term outcome and renal prognosis of late-onset
      PTLDs both before and after the era of rituximab. RESULTS: Before 2000, 38% of
      the patients underwent surgery and 76% received chemotherapy either immediately
      or after surgery. After 2000, rituximab was administrated to 70% of the patients
      either alone (23%) or in combination with chemotherapy (77%). Chemotherapy alone
      was administrated in 26% of the cases. Before and after 2000, complete remission
      was achieved in 38 and 87% of the cases, respectively (P = 0.0005). The 5-year
      overall survival (OS) was 33.3 and 69% (P = 0.003), and 5-year disease-free
      survival was 37.5 and 80%, respectively (P = 0.19). Renal function was preserved
      in 70% of the cases at the end of the follow-up. CONCLUSIONS: This study shows an
      increase in OS and low graft loss for patients with late-onset PTLDs during the
      last decade, which may be attributed to multiple changes in clinical practice,
      including a more standardized treatment and the use of rituximab in combination
      with chemotherapy.

PMID- 23129825
TI  - Colorectal cancer screening in kidney disease patients: working backwards.

PMID- 23129826
TI  - Secreted Klotho and FGF23 in chronic kidney disease Stage 1 to 5: a sequence
      suggested from a cross-sectional study.
AB  - BACKGROUND: Klotho and fibroblast growth factor 23 (FGF23) are key regulators of
      mineral metabolism in renal insufficiency. FGF23 levels have been shown to
      increase early in chronic kidney disease (CKD); however, the corresponding
      soluble Klotho levels at the different CKD stages are not known. METHODS: Soluble
      Klotho, FGF23, parathyroid hormone (PTH), 1,25-dihydroxy vitamin D(3) (1,25D) and
      other parameters of mineral metabolism were measured in an observational cross
      sectional study in 87 patients. Locally weighted scatter plot smoothing function
      of these parameters were plotted versus estimated glomerular filtration rate
      (eGFR) to illustrate the pattern of the relationship. Linear and non-linear
      regression analyses were performed to estimate changes in mineral metabolism
      parameters per 1mL/min/1.73 m(2) decline. RESULTS: In CKD 1-5, Klotho and 1,25D
      linearly decreased, whereas both FGF23 and PTH showed a baseline at early CKD
      stages and then a curvilinear increase. Crude mean Klotho level declined by 4.8
      pg/mL (95% CI 3.5-6.2 pg/mL, P < 0.0001) and 1,25D levels by 0.30 ng/L (95% CI
      0.18-0.41 ng/L, P < 0.0001) as GFR declined by 1 mL/min/1.73 m(2). After
      adjustment for age, gender, serum 25-hydroxyvitamin D levels and concomitant
      medications (calcium, supplemental vitamin D and calcitriol), we estimated that
      the mean Klotho change was 3.2 pg/mL (95% CI 1.2-5.2 pg/mL, P = 0.0019) for each
      1 mL/min/1.73 m(2) GFR change. FGF23 departed from the baseline at an eGFR of 47
      mL/min/1.73 m(2) (95% CI 39-56 mL/min/1.73 m(2)), whereas PTH departed at an eGFR
      of 34 mL/min/1.73 m(2) (95% CI 19-50 mL/min/1.73 m(2)). CONCLUSIONS: Soluble
      Klotho and 1,25D levels decrease and FGF23 levels increase at early CKD stages,
      whereas PTH levels increase at more advanced CKD stages.

PMID- 23129827
TI  - RRT treatment for AKI: is more always better?

PMID- 23129828
TI  - Maternal intolerance of uncertainty, anxiety, and adherence with food challenge
      referrals.
AB  - Anxiety regarding food challenges may serve an important role in parents'
      decisions to adhere to their child's food challenge referrals. This study
      examined the role of intolerance of uncertainty in food challenge referral
      adherence by assessing state/trait anxiety among mothers whose children were
      referred for a food challenge. Mothers whose children passed a food challenge
      reported significant decreases in anxiety regarding allergic reactions, but
      intolerance of uncertainty did not predict adherence. Trust in the physician was
      a primary reason mothers attended the food challenge, suggesting that physicians
      should consider the impact of the physician-patient relationship when treating
      these families. 

PMID- 23129829
TI  - Type D (distressed) personality and its assessment with the DS14 in Lithuanian
      patients with coronary artery disease.
AB  - We examined Type D personality (combination of negative affectivity with social
      inhibition) and its assessment with the DS14 in 543 Lithuanian coronary patients.
      Psychometric analyses confirmed the two-factor structure, internal consistency
      (alpha = 0.84/alpha = 0.75), and test-retest reliability (r = 0.69/0.81) of the
      DS14 negative affectivity and inhibition components. Negative affectivity
      correlated (r = -0.58) with emotional stability and social inhibition (r = -0.46)
      with extraversion; correlations with other Big-Five traits ranged between r = 
      0.11 and -0.19. Type D patients (34%) had a ninefold increased odds of depression
      (95% confidence interval = 5.01-17.36) and a fivefold increased odds of anxiety
      (95% confidence interval = 3.47-7.97). These findings support the validity of the
      Type D construct in Lithuania. 

PMID- 23129830
TI  - 'In two minds'--socially motivated self-harm is perceived as less serious than
      internally motivated: a qualitative study of youth justice staff.
AB  - Community-based young offenders are at high risk of self-harm and unlikely to be
      in contact with mental health services. Semi-structured interviews with community
      youth justice staff and a content analysis of 50 records of self-harm not only
      revealed staff concerns about the impact of stigma on disclosure and service use,
      but also found dismissive attitudes towards socially motivated self-harm, which
      was equated with lower suicide risk and less emotional distress. Efforts to
      improve identification of self-harm will need to address the perceived - and
      false - distinction between 'genuine' and socially motivated self-harm. 

PMID- 23129831
TI  - Gay and bisexual men's human papillomavirus vaccine intentions: a theory-based
      structural equation analysis.
AB  - In this study, we examined the structural relationships among constructs from the
      Health Belief Model as they relate to human papillomavirus vaccine intentions in
      young gay and bisexual men in the United States (N = 183). A model was identified
      that fit the data well and accounted for 56% of the variance in vaccine
      intentions. Perceived benefits and barriers were the most proximate predictors of
      intentions, whereas knowledge and perceived threat exerted only indirect
      influence. Clarifying the propositional structures within the Health Belief Model
      can help to advance our understanding of human papillomavirus-related cognitions
      and behaviors and inform vaccine promotion programs. 

PMID- 23129832
TI  - Thriving in the shadow of the 2008 Sichuan earthquake: two studies on resilience
      in adolescents.
AB  - The objective of the current study was to explore the relationship between
      resilience and psychological adjustment in Chinese adolescents who experienced
      the 2008 Sichuan earthquake. Study 1 compared the scores and factor structures on
      the Resilience Scale for Chinese Adolescents for 1436 adolescents, who were
      divided into a high-adversity group and a low-adversity group. The results showed
      that resilience following exposure to an earthquake included cognitive and
      emotive components. In Study 2, 311 Chinese adolescents who resided in the most
      severely affected areas were surveyed at 15 months (T1) and 20 months (T2)
      following the earthquake. The results revealed that resilience mediated the
      relationship between positive future expectations at T1 and adjustment at T2. 

PMID- 23129833
TI  - The social sharing of emotions in HIV/AIDS: a comparative study of HIV/AIDS,
      diabetic and cancer patients.
AB  - Studies have shown that chronic illness patients encounter difficulties in the
      social sharing of emotions. Do HIV/AIDS patients present distinguishing traits in
      the inhibition of illness and non-illness-related emotions? The differences in
      the social sharing of emotion between 35 HIV/AIDS, 35 diabetic and 34 cancer
      outpatients were studied. A questionnaire assessed illness-related emotions,
      social sharing of emotion and emotional inhibition. The HIV/AIDS group
      significantly presented superior scoring in shame, guilt and non-sharing of
      illness-related emotions, lower frequencies of social sharing of emotion and less
      sharing partners. These findings could lead to future research examining the
      emotional expression of guilt and shame in HIV/AIDS. 

PMID- 23129834
TI  - The association between stress and physical health in parents caring for children
      with intellectual disabilities is moderated by children's challenging behaviours.
AB  - The present study examined the moderating role of social support and challenging
      behaviour on the stress-physical health relationship in parents caring for
      children with intellectual disabilities. Parents of children with intellectual
      disabilities (n = 70) reported more physical health problems compared to control
      parents (n = 45) and were more likely to visit their general practitioner.
      Furthermore, challenging behaviours, but not social support, moderated this
      association: parents of children with intellectual disabilities reported poorer
      physical health when both challenging behaviours and stress were perceived to be
      high. These findings suggest that interventions need to be directed towards
      ameliorating the impact of challenging behaviours. 

PMID- 23129835
TI  - Life satisfaction and feeling in control: indicators of successful aging predict
      mortality in old age.
AB  - Life satisfaction and control beliefs are established indicators of successful
      aging and predict mortality. However, it has not yet been examined whether they
      independently predict mortality or interact. We examined main and interaction
      effects using Cox proportional hazards models in a sample of older adults (N =
      1402; age range: 65-91). Only the interaction of life satisfaction and control
      beliefs significantly predicted mortality when controlling for socio-demographic
      variables and health. These findings suggest that detrimental effects of low
      control beliefs can be buffered by life satisfaction, and unexpectedly, that high
      levels of both factors are not most protective against mortality. 

PMID- 23129836
TI  - Composite peripheral T-cell lymphoma not otherwise specified, and B-cell small
      lymphocytic lymphoma presenting with hemophagocytic lymphohistiocytosis.
AB  - We report a case of a 68-year-old female patient who developed hemophagocytic
      lymphohistiocytosis (HLH) secondary to peripheral T-cell lymphoma (PTCL) not
      otherwise specified (NOS) that developed in the setting of treatment-resistant B
      cell small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL). The
      patient's B-cell lymphoma had a good initial response to chemotherapy for 4
      years, after which it became less responsive and was thought to have undergone
      transition to a higher-grade lymphoma. Different regimens of chemoradiotherapy
      were then tried with modest response until the patient presented 3 years later
      with signs and symptoms of HLH. The patient died 1 month later, and an autopsy
      was performed. Significant para-aortic lymphadenopathy and splenomegaly were
      found. Microscopic, immunohistochemical and molecular evaluations confirmed the
      presence of composite B-cell and T-cell lymphoma in the para-aortic enlarged
      lymph nodes. Bone marrow examination showed hemophagocytosis, and the liver
      demonstrated infiltration by activated macrophages with hepatocellular necrosis.
      This report highlights the importance of searching for a possible underlying T
      cell lymphoma in light of HLH. Different theories have been proposed to explain
      the rare occurrence of concurrent B- and T-cell lymphomas, but the development of
      HLH in this patient highlights the importance of immune dysregulation as a
      proposed mechanism to explain some cases of composite lymphomas. A review of the
      literature and discussion of the relative merits of these hypotheses are
      presented in the context of this case.

PMID- 23129837
TI  - Desmoplastic medulloblastoma arising from an ovarian teratoma: a case report and
      review of the literature.
AB  - The primary neuroectodermal tumor of the ovary is extremely rare, and it
      manifests in 3 forms: differentiated, primitive, and anaplastic. The
      medulloblastoma belongs to the subgroup of primitive neuroectodermal tumor of the
      ovary. Only 3 cases of ovarian medulloblastoma have been reported in the
      literature, and all of them are presented without information about the specific
      pathological subtype. We present the fourth case of a 26-year-old woman who
      presented with abdominal fullness for months. Ultrasound exam showed a right
      adnexal mass with cystic feature and foci solid components. A partial
      oophorectomy was performed, and the mass was a desmoplastic medulloblastoma
      arising from an ovarian teratoma. 

PMID- 23129838
TI  - Microscopic Kaposiform hemangioendothelioma with extensive lymphangiomatosis: an
      extraordinary example of an unusual entity.
AB  - Kaposiform hemangioendothelioma (KHE) is presently classified as a vascular
      neoplasm of intermediate malignant potential. The clinical course of large, deep
      seated tumors is frequently complicated by consumptive coagulopathy and life
      threatening hemorrhage, while superficial tumors tend to behave in an indolent
      manner, with no known reports of distant metastasis. We describe an unusual
      example of KHE occurring as an incidental microscopic finding, within a
      background of extensive lymphangioma-like changes. The patient underwent 4
      intralesional excisions over a period of 6 years, and the Kaposiform component
      accounts for less than 5% of the overall tissue excised. The patient remains
      clinically well with residual disease 5 years after conservative surgery, and
      there has been no evidence of regional or distant metastasis. Based on existing
      literature, it appears doubtful that KHE has any metastatic potential at all,
      which calls into question the appropriateness of its place in the spectrum of
      malignant vascular neoplasms.

PMID- 23129839
TI  - Modification of smoke toxicant yields alters the effects of cigarette smoke
      extracts on endothelial migration: an in vitro study using a cardiovascular
      disease model.
AB  - Endothelial damage plays a key role in atherosclerosis and this is impacted upon
      by numerous risk factors including cigarette smoking. A potential measure to
      reduce the cardiovascular burden associated with smoking is to reduce smoke
      toxicant exposure. In an in vitro endothelial damage repair assay, endothelial
      cell migration was inhibited by cigarette smoke particulate matter (PM) generated
      from several cigarette types. This inhibition was reduced when cells were exposed
      to PM from an experimental cigarette with reduced smoke toxicant levels. As a
      number of toxicants induce oxidative stress and since oxidative stress may link
      cigarette smoke and endothelial damage, we hypothesized that PM effects were
      dependent on elevated cellular oxidants. However, although PM-induced cellular
      oxidant production could be inhibited by ascorbic acid or n-acetylcysteine, both
      these antioxidants were without effect on migration responses to PM. Furthermore,
      reactive oxygen species production, as indicated by dihydroethidium fluorescence,
      was not different in cells exposed to smoke from cigarettes with different
      toxicant levels. In summary, our data demonstrate that a cardiovascular disease
      related biological response may be modified when cells are exposed to smoke
      containing different levels of toxicants. This appeared independent of the
      induction of oxidative stress.

PMID- 23129840
TI  - Dual degrees and career paths.

PMID- 23129841
TI  - A call for greater policy emphasis and public health applications in pharmacy
      education.

PMID- 23129842
TI  - Hiring residents as faculty members: dancing with the stars.

PMID- 23129843
TI  - Maintaining pharmacy education's research focus as the academy expands.

PMID- 23129844
TI  - Pharmacy residencies and dual degrees as complementary or competitive advanced
      training opportunities.
AB  - The impact of pharmacy practice has been enhanced through additional graduate
      training opportunities, such as pharmacy residencies and dual-degree programs.
      This article compares and contrasts key aspects of pharmacy residencies and dual
      degree programs, as well as examines the efforts of US colleges and schools of
      pharmacy in promoting these advanced training opportunities on their Web sites.
      Pharmacy residencies and dual-degree programs are complementary opportunities
      that allow student pharmacists to gain advanced knowledge and specialized skills
      beyond the traditional Doctor of Pharmacy (PharmD) degree. The combination of
      these credentials can be highly advantageous in a variety of practice settings.
      As pharmacists collaborate with healthcare providers and professionals from other
      disciplines, more support is needed to expand the availability and use of these
      cross-profession, advanced training opportunities to enhance the future of the
      pharmacy profession.

PMID- 23129845
TI  - Bachelor's degree programs in clinical pharmacy in China.
AB  - This paper describes the status of the bachelor's degree in clinical pharmacy
      education in China, with particular focus on educational institutions, programs,
      and curricula. The authors conducted a systematic literature review of clinical
      pharmacy education articles published from 2006 to 2011. To ensure the
      completeness of the investigation, an e-mail was sent or telephone call made
      directly to the colleges whose curriculum information could not be obtained by
      the above methodology. Twenty-three colleges offered a program in clinical
      pharmacy education in 2011. The colleges award either a bachelor of science or a
      bachelor of medicine degree with programs ranging from 4 to 5 years in duration.
      The 5-year BS degree program was most popular. Although the number of clinical
      pharmacy programs in China has steadily increased, more graduates and
      standardization of curricula are needed to meet the country's steadily expanding
      need for quality health care.

PMID- 23129846
TI  - Syrian pharmacy students' intentions and attitudes toward postgraduate education.
AB  - OBJECTIVE: To investigate Syrian pharmacy students' intentions and attitudes
      toward postgraduate study, and to determine and evaluate the factors that
      influence their preferences. METHODS: A questionnaire was developed and used to
      collect data from final-year bachelor of pharmacy (BPharm) students at Damascus
      University. RESULTS: Of the 265 students who responded to the survey,
      approximately 50% intended to work, 25% intended to pursue further study, and 25%
      were undecided. Personal fulfillment was the factor that most influenced
      students' intentions concerning future education. Men were more concerned over
      their financial future, while women's intentions were more influenced by
      scientific issues. The 3 most preferred pharmaceutical areas of further study
      were biochemistry and laboratory diagnosis, pharmaceutics and pharmaceutical
      industry, and clinical pharmacy. More students favored pursuing graduate school
      abroad rather than in Syria. The majority of those who intended to enroll in
      local graduate programs were interested in academic programs while less than a
      fifth favored residency programs. CONCLUSIONS: The graduate programs in Syria do
      not appear to satisfy pharmacy students' ambitions or have the capacity to
      accommodate the growing demand associated with the rapid increase in the number
      of pharmacy graduates in the country. Consequently, a majority of students prefer
      to pursue postgraduate study abroad.

PMID- 23129847
TI  - Assessment of full-time faculty preceptors by colleges and schools of pharmacy in
      the United States and Puerto Rico.
AB  - OBJECTIVE: To identify the manner in which colleges and schools of pharmacy in
      the United States and Puerto Rico assess full-time faculty preceptors. METHODS:
      Directors of pharmacy practice (or equivalent title) were invited to complete an
      online, self-administered questionnaire. RESULTS: Seventy of the 75 respondents
      (93.3%) confirmed that their college or school assessed full-time pharmacy
      faculty members based on activities related to precepting students at a practice
      site. The most commonly reported assessment components were summative student
      evaluations (98.5%), type of professional service provided (92.3%), scholarly
      accomplishments (86.2%), and community service (72.3%). Approximately 42% of
      respondents indicated that a letter of evaluation provided by a site-based
      supervisor was included in their assessment process. Some colleges and schools
      also conducted onsite assessment of faculty members. CONCLUSIONS: Most colleges
      and schools of pharmacy assess full-time faculty-member preceptors via summative
      student assessments, although other strategies are used. Given the important role
      of preceptors in ensuring students are prepared for pharmacy practice, colleges
      and schools of pharmacy should review their assessment strategies for full-time
      faculty preceptors, keeping in mind the methodologies used by other institutions.

PMID- 23129848
TI  - The impact of student pharmacists at health fair events.
AB  - OBJECTIVES: To evaluate student pharmacists' impact on health fair participant
      knowledge of selected disease states and to evaluate the intent of health fair
      participants with abnormal screening results to seek follow-up care within 1
      month of screening. METHODS: Health fair participants were assessed for changes
      in their knowledge of specific diseases before and after screenings.
      Participants' intent to seek health care was assessed through a survey instrument
      developed using Rosenstock's Health Belief Model. RESULTS: Increases in
      participant knowledge of hypertension, diabetes, dyslipidemia, and body mass
      index were significant, and 78% of participants with abnormal results intended to
      contact a provider. CONCLUSIONS: Student pharmacists' had a positive impact on
      health fair participants' disease knowledge and intent to follow up with a
      provider.

PMID- 23129849
TI  - Interprofessional workshop to improve mutual understanding between pharmacy and
      medical students.
AB  - OBJECTIVE: To measure changes in pharmacy and medical students' physician
      pharmacist collaboration scores resulting from a workshop designed to promote
      understanding of the others' roles in health care. METHODS: More than 88% of
      first-year pharmacy (n = 215) and medical (n = 205) students completed the Scale
      of Attitudes Toward Physician-Pharmacist Collaboration on 3 occasions in order to
      establish a baseline of median scores and to determine whether the scores were
      influenced by an interprofessional workshop. RESULTS: Participation in the
      interprofessional workshop increased pharmacy students' collaboration scores
      above baseline (p=0.02) and raised the scores of medical students on the
      education component of the collaboration survey instrument (p=0.015). The
      collaboration scores of pharmacy students greatly exceeded those of medical
      students (p<0.0001). CONCLUSION: A workshop designed to foster interprofessional
      understanding between pharmacy and medical students raised the physician
      pharmacist collaboration scores of both. Crucial practical goals for the future
      include raising the collaboration scores of medical students to those of pharmacy
      students.

PMID- 23129850
TI  - Diversity characteristics of the 2008-2009 pharmacy college application service
      applicant pool.
AB  - OBJECTIVE: To characterize the 2008-2009 Pharmacy College Application Service
      (PharmCAS) applicant pool in terms of diversity-related variables compared with
      admissions-related variables. METHODS: The relationships between the diversity
      variables of ethnicity, gender, parental education, and prepharmacy education,
      and the admissions-related variables of grade point average (GPA), pharmacy
      college admission test (PCAT) score, and acceptance rates were evaluated.
      RESULTS: There were 16,246 applicants to PharmCAS during the 2008-2009 pharmacy
      college and school admission cycle. Female applicants and non-underrepresented
      minorities (non-URMs) achieved higher mean GPAs, and male applicants and non-URMs
      had higher mean PCAT scores. Higher parental education was associated with higher
      mean GPA and PCAT scores. Mean PCAT score and GPA increased as prepharmacy
      education increased, with the exception of a bachelor's degree, which was
      associated with a lower GPA. Acceptance rates were higher among female
      applicants, non-URMs, and applicants with higher prepharmacy education and
      parental education. CONCLUSIONS: Female applicants, non-URMs, applicants with
      higher than a bachelor's degree, and applicants whose parents attained a doctoral
      degree were associated with higher mean GPAs and PCAT scores and were accepted to
      a higher proportion of the colleges and schools to which they applied. Colleges
      and schools of pharmacy can use these data as a benchmark when evaluating
      admissions processes.

PMID- 23129851
TI  - The influence of a patient-counseling course on the communication apprehension,
      outcome expectations, and self-efficacy of first-year pharmacy students.
AB  - OBJECTIVES: To evaluate first-year doctor of pharmacy (PharmD) students'
      communication apprehension, outcome expectations, and self-efficacy for
      communication over the duration of a 15-week patient-counseling course. DESIGN:
      First-year PharmD students (n=94) were asked to complete a 47-item, self
      administered questionnaire on 3 occasions over the duration of the
      Nonprescription Drugs/Patient-Counseling course during the fall 2009 and 2010
      semesters. ASSESSMENT: Eighty-seven of 94 students completed the survey
      instrument across data collection periods. There were significant reductions in
      total communication apprehension scores and in the communication apprehension
      subscores for meetings and public speaking, and significant increases in self
      efficacy over time. No differences were found for outcome expectations of
      communication scores or the subscores for interpersonal conversations and group
      discussion. CONCLUSIONS: Communication apprehension may be decreased and self
      efficacy for communication increased in first-year PharmD students through a 15
      week Nonprescription Drugs/Patient-Counseling course using small-group practice
      sessions, case studies, and role-play exercises in conjunction with classroom
      lectures.

PMID- 23129852
TI  - Small-team active learning in an integrated pharmacokinetics course series.
AB  - OBJECTIVES: To implement a pharmacokinetics curriculum that used small-team
      active learning and assess students' perceptions. DESIGN: The course design and
      delivery were based on delivery of Student Team lecture followed by concept
      reinforcement through problem-based learning sessions. Course faculty members
      facilitated classroom and problem-based learning discussions to promote an active
      learning environment. ASSESSMENT: An anonymous survey instrument was administered
      to students prior to and following completion of the pharmacokinetics course.
      Students reported a significant decrease in anxiety from 67% to 44% related to
      working in small teams upon completion of the course. However, students
      maintained negative perceptions related to peer teaching, with 80% of students
      reporting anxiety related to receipt of course information from peers. The course
      had a positive impact on students' ability to apply concepts to case-based
      scenarios, but little impact on their perceived ability to identify and
      critically evaluate new material and present that material to their peer team.
      CONCLUSIONS: The team-based structure defined herein for delivery of a
      pharmacokinetics curriculum offers students a tangible method to increase their
      comfort and confidence in the application of pharmacokinetic concepts in therapy.

PMID- 23129853
TI  - An introductory interprofessional exercise for healthcare students.
AB  - OBJECTIVE: To evaluate healthcare students' perceptions of an introductory
      interprofessional exercise and their team dynamics. DESIGN: A workshop was
      developed, combining second-year medical students, fourth-year nursing students,
      and third-year pharmacy students to work as an interdisciplinary team. The teams
      alternated between working together on patient cases focusing on chronic
      obstructive pulmonary disease and asthma, and on the evaluation of standardized
      pneumonia patients. Teams were given the patients' health information and no
      other instructions. A faculty member and the standardized patient evaluated the
      students using a teamwork global rating scale. ASSESSMENT: Student survey results
      showed a positive response to interprofessional teamwork. The faculty members and
      standardized patients reported that the students worked as a cohesive unit and
      demonstrated good team communication. CONCLUSIONS: This introductory
      interprofessional experience had a positive impact on the students' understanding
      of collaboration and teamwork. This type of experience will help students foster
      future collaborations as healthcare providers.

PMID- 23129854
TI  - Professional development webinars for pharmacists.
AB  - OBJECTIVES: To evaluate pharmacists' satisfaction with and reasons for enrolling
      in a series of continuing education webinars. DESIGN: Webinars intended to
      provide timely and practical information for practicing pharmacists on a specific
      therapeutic area were created and presented monthly throughout 2011. ASSESSMENT:
      Survey responses of volunteers who completed at least 1 webinar were positive
      regarding the quality of the programming and the method of delivery. No
      significant differences were found in demographics or reasons for enrolling
      between participants who completed a single webinar and those who completed 2 or
      more. CONCLUSIONS: While the webinars received positive evaluations for quality,
      value, and relevance, the limited average number of webinars attended by each
      pharmacist was a concern, and several tactics will be implemented to address
      scheduling conflicts and other deterrents to repeat participation.

PMID- 23129855
TI  - A medical mission to Guatemala as an advanced pharmacy practice experience.
AB  - OBJECTIVE: To describe the development and outcomes of an advanced pharmacy
      practice experience (APPE) for a medical mission trip to Guatemala. DESIGN: Pre
      mission preparation and post-mission reflection activities were combined with in
      country activities to create a 5-week APPE. During the 10-day medical mission
      trip, pharmacy students dispensed medications, counseled patients, conducted
      quality improvement assessments, and presented their findings and experiences as
      part of an interdisciplinary health care team. ASSESSMENT: The students who
      completed the mission trip met the objectives of the APPE and reported
      substantial learning in the areas of interdisciplinary teamwork and cultural
      competency. All students' scores on the Inventory for Assessing the Process of
      Cultural Competence-Student Version (IAPCC-SV) increased. The majority (81%) of
      student-generated quality improvement recommendations were implemented by the
      mission team. CONCLUSIONS: The medical mission APPE provided a rich learning
      environment for pharmacy students and resulted in modifications to the medical
      mission operation. This type of APPE could be implemented in other colleges of
      pharmacy via formation of partnerships with established medical mission teams as
      this one was.

PMID- 23129856
TI  - An assessment model for multidisciplinary, team-taught integrated pharmacy
      courses.
AB  - OBJECTIVE: To design and implement an assessment model to effectively deliver
      integrated multidisciplinary team-taught pharmacy courses. DESIGN: An assessment
      model was developed for an integrated pharmacotherapeutics course that focused on
      writing detailed learning objectives and matching them to examination questions.
      Qualitative assessment of learning objectives, course-embedded quantitative
      assessment, and objective assessments of examinations by subdiscipline were
      performed. ASSESSMENT: This model was assessed through course evaluations,
      faculty and course coordinator perceptions, and faculty and student focus groups,
      which provided data that facilitated effective integration and identified gaps
      and overlaps in content. The assessment of the examinations by discipline and the
      embedded quantitative assessment results identified previously unassessed and
      poorly performing objectives. Students believed the course contributed
      significantly to their professional growth and that it was one of the best
      integrated courses, based in part on the improved teaching methods. CONCLUSIONS:
      A systematic assessment model that was developed for the effective delivery of
      multidisciplinary team-taught courses can be standardized and delivered despite
      changes in instructors for subsequent course offerings.

PMID- 23129857
TI  - Creation of medicinal chemistry learning communities through enhanced technology
      and interdisciplinary collaboration.
AB  - Objectives. To build an integrated medicinal chemistry learning community of
      campus and distance pharmacy students though the use of innovative technology and
      interdisciplinary teaching.Design. Mechanisms were implemented to bring distance
      students into campus-based medicinal chemistry classrooms in real time, stimulate
      interaction between instructors and various student cohorts, and promote group
      work during class. Also, pharmacy clinician colleagues were recruited to
      contribute to the teaching of the 3 medicinal chemistry courses.Assessment.
      Student perceptions on the value of technology to build community and advance
      learning were gleaned from course evaluations, in class feedback, and
      conversations with class officers and student groups. Responses on a survey of
      second-year students confirmed the benefits of interdisciplinary content
      integration on engagement and awareness of the connection between drug chemistry
      and pharmacy practice. A survey of clinician colleagues who contributed to
      teaching the 3 medicinal chemistry courses found their views were similar to
      those of students.Conclusions. The purposeful use of technology united learners,
      fostered communication, and advanced content comprehension in 3 medicinal
      chemistry courses taught to campus and distance students. Teaching collaboration
      with pharmacy clinicians enhanced learner interest in course content and provided
      insight into the integrated nature of the profession of pharmacy.

PMID- 23129859
TI  - Geographical composition of the editorial boards of leading pharmacy journals.

PMID- 23129860
TI  - Interprofessional education: thoughts of a current pharmacy resident.

PMID- 23129861
TI  - Report of the 2011-2012 AACP Special Advisory Committee on Research and Graduate
      Education.

PMID- 23129862
TI  - Hospital pharmacy in Canada: ahead of the curve.

PMID- 23129863
TI  - Stability of azacitidine in sterile water for injection.
AB  - BACKGROUND: The product monograph for azacitidine states that once reconstituted,
      the drug may be held for only 30 min at room temperature or 8 h at 4 degrees C.
      Standard doses result in wastage of a portion of each vial, and the cost of this
      wastage is significant, adding about $156 000 to annual drug expenditures at the
      authors' institution. OBJECTIVE: To evaluate the stability of azacitidine after
      reconstitution. METHODS: Vials of azacitidine were reconstituted with sterile
      water for injection. At the time of reconstitution, the temperature of the
      diluent was 4 degrees C for samples to be stored at 4 degrees C or -20 degrees C
      and room temperature for samples to be stored at 23 degrees C. Solutions of
      azacitidine (10 or 25 mg/mL) were stored in polypropylene syringes and glass
      vials at room temperature (23 degrees C), 4 degrees C, or -20 degrees C. The
      concentration of azacitidine was determined by a validated, stability-indicating
      liquid chromatographic method in serial samples over 9.6 h at room temperature,
      over 4 days at 4 degrees C, and over 23 days at -20 degrees C. The recommended
      expiry date was determined on the basis of time to reach 90% of the initial
      concentration according to the fastest observed degradation rates (i.e., lower
      limit of 95% confidence interval). RESULTS: Azacitidine degradation was very
      sensitive to temperature but not storage container (glass vial or polypropylene
      syringe). Reconstitution with cold sterile water reduced degradation. At 23
      degrees C, 15% of the initial concentration was lost after 9.6 h; at 4 degrees C,
      32% was lost after 4 days; and at -20 degrees C, less than 5% was lost after 23
      days. CONCLUSIONS: More than 90% of the initial azacitidine concentration will be
      retained, with 97.5% confidence, if, during the life of the product, storage at
      23 degrees C does not exceed 2 h, storage at 4 degrees C does not exceed 8 h, and
      storage at -20 degrees C does not exceed 4 days. These expiry dates could
      substantially reduce wastage and cost where the time between doses does not
      exceed 4 days.

PMID- 23129864
TI  - Ascertaining problems with medication histories.
AB  - BACKGROUND: Accurate and complete medication histories are not always obtained in
      clinical practice. OBJECTIVE: This qualitative research study was undertaken to
      explore the barriers to and facilitators of obtaining accurate medication
      histories. METHODS: Individual interviews, based on a structured interview guide,
      were conducted with 25 patients from both inpatient and ambulatory care clinic
      settings. Focus groups, based on a semistructured interview guide, were conducted
      with pharmacists, medical residents, and nurses. Transcribed data were analyzed
      by forming coded units and assessing these units for emerging themes. RESULTS:
      Major themes that emerged from the patient interviews included patient ownership
      of health and medication knowledge (with knowledge of medications and their side
      effects and how to take medications being seen as important), patient-specific
      strategies to improve medication histories (e.g., use of regularly updated
      medication lists), and suggestions for system-level facilitators to improve
      medication histories (e.g., centralized databases of medication histories,
      increased patient education regarding the use and purpose of medications). Major
      themes also emerged from focus groups with health care professionals, including
      shared responsibility for medication history-taking among all 3 health care
      professions, perceptions about the barriers to medication history-taking
      (including patients not knowing their medications and not bringing their
      medication lists), and suggestions to improve medication histories (e.g.,
      educating patients to bring medication vials to hospital admissions and
      appointments, using a centralized computer database for medication histories).
      CONCLUSIONS: Key recommendations resulting from this study include using
      standardized documentation techniques for medication histories, recording of
      medication history information in centralized electronic databases, educating
      patients to bring medications to every health care visit, and establishing
      criteria for pharmacist referral for cases involving complex medication
      histories.

PMID- 23129865
TI  - Taste and/or Odour Disturbances in Pediatric Patients Undergoing IV Flush with
      Normal Saline Administered by Prefilled Syringe.
AB  - BACKGROUND: At the Children's Hospital of Eastern Ontario, more than 6000
      inpatients per year undergo IV saline flushes by prefilled syringe to assess and
      maintain patency of IV tubing. In studies involving adults, it has been reported
      that volatile substances may leach from syringe materials into the saline,
      leading to taste and/or odour disturbances. OBJECTIVE: To determine the incidence
      of taste and/or odour disturbances in pediatric patients after flushing of IV
      tubing with 0.9% sodium chloride (normal saline [NS]) from prefilled syringes.
      METHODS: Inpatients aged 5-18 years who had undergone routine flushing of central
      or peripheral IV tubing with commercially available prefilled NS syringes were
      interviewed. Children aged 5-10 years used a visual hedonic scale to rate taste
      and odour sensations, and those aged 11-18 years used a numeric rating scale.
      RESULTS: During the study period (April to July 2011), a total of 104 pediatric
      inpatients (21 aged 5-10 years and 83 aged 11-18 years) underwent NS flushing of
      central (10 patients [10%]) or peripheral (94 patients [90%]) tubing. For 100 of
      these patients, BD Posiflush NaCl 0.9% 10-mL sterile prefilled syringes were
      used, and for 4 patients BD Saline XS NaCl 0.9% 10-mL sterile prefilled syringes
      were used. Taste and/or odour disturbances were reported by 76 (73%) of the
      patients. Twelve patients described more than one taste or odour sensation. Taste
      and odour disturbances were detected by children in both age groups. CONCLUSIONS:
      Flushing of IV tubing with prefilled NS syringes resulted in taste and/or odour
      disturbances in a pediatric population.

PMID- 23129866
TI  - Management of chronic obstructive pulmonary disease in patients admitted to a
      tertiary care centre for exacerbation of their disease.
AB  - BACKGROUND: Acute exacerbation of chronic obstructive pulmonary disease (COPD) is
      associated with an accelerated decline in lung function and a significant
      decrease in health status. Maintenance therapy with respiratory medications can
      reduce the risk of such exacerbations. OBJECTIVE: To determine whether
      respiratory maintenance medications were being prescribed in accordance with the
      2007 COPD guidelines of the Canadian Thoracic Society for patients admitted to
      hospital for acute exacerbation of COPD. METHODS: A chart review was conducted
      for admissions to the Centre hospitalier universitaire de Sherbrooke, in
      Sherbrooke, Quebec, for acute exacerbation of COPD (according to diagnostic codes
      in the International Statistical Classification of Diseases and Related Health
      Problems, 10th revision) between January 1, 2008, and January 31, 2011. Data were
      extracted from patients' medical charts concerning respiratory medications
      prescribed before the admission, during the hospital stay, and at discharge.
      RESULTS: A total of 846 hospital admissions involving 561 patients were reviewed.
      In almost 70% of admissions for which data were available on respiratory
      medications prescribed before the admission, during the hospital stay, and at
      discharge (238/341 [69.8%]), a combination of 3 medications was prescribed at
      discharge: tiotropium, a long-acting beta(2) agonist, and an inhaled
      corticosteroid. For more than 80% of the admissions, a prescription for at least
      one inhaled long-acting bronchodilator was documented both on admission and at
      discharge. Few patients had a prescription for inhaled corticosteroid without
      long-acting beta(2) agonist, but the number of admissions with a prescription for
      regular use of systemic corticosteroids increased at discharge. CONCLUSIONS:
      Respiratory medications were generally prescribed in accordance with Canadian
      COPD guidelines, but improvements could be made regarding use of the combination
      of tiotropium, long-acting beta(2)agonist, and inhaled corticosteroid, as well as
      long-term use of systemic corticosteroids.

PMID- 23129867
TI  - Dosing and monitoring of methadone in pregnancy: literature review.
AB  - BACKGROUND: The pharmacokinetics of methadone is altered during pregnancy, but
      the most appropriate dosing and monitoring regimen has yet to be identified.
      OBJECTIVE: To review dosing and monitoring of methadone therapy in pregnancy.
      METHODS: A literature search was performed in several databases (PubMed, MEDLINE,
      Embase, International Pharmaceutical Abstracts, and the Cochrane Database of
      Systematic Reviews) from inception to May 2012. The search terms were
      "methadone", "pregnancy", "pharmacokinetic", "clearance", "metabolism",
      "therapeutic drug monitoring", and "methadone dosing". Additional papers were
      identified by searching the bibliographies of primary and review articles. All
      English-language primary articles related to methadone pharmacokinetics in
      pregnancy were included. Articles not related to maternal outcomes were excluded.
      RESULTS: The literature search yielded 1 case report and 10 studies discussing
      use of methadone by pregnant women. Methadone pharmacokinetics in pregnancy has
      been studied in 3 pharmacokinetic trials, and split dosing of methadone in
      pregnant women has been described in 1 case report and 3 dosing trials. Only 4
      trials evaluated monitoring of methadone concentration in pregnancy. The studies
      included in this review confirm that methadone pharmacokinetics is altered in
      pregnancy and is potentially correlated with increases in maternal withdrawal
      symptoms. Insufficient evidence is available to warrant routine monitoring of
      serum methadone concentrations in pregnant women with opioid dependence.
      CONCLUSIONS: Few studies of methadone pharmacokinetics and therapeutic drug
      monitoring are available for pregnant women with opioid dependence. Although it
      is known that methadone pharmacokinetics is altered in pregnancy, there is
      insufficient evidence to guide dosage adjustments and serum concentration
      monitoring. Until further studies are available, regular follow-up of maternal
      withdrawal symptoms and empiric dosage adjustments throughout pregnancy are still
      recommended.

PMID- 23129868
TI  - Does outcome reporting bias "cause" cancer? Risks associated with hidden data on
      Angiotensin receptor blockers.
AB  - Conflicting reports have been published regarding the influence of angiotensin
      receptor blockers (ARBs) on the incidence of cancer. One meta-analysis reported a
      1% absolute increase in the incidence of cancer associated with ARBs over 4
      years. Contrasting findings were reported in an industry-sponsored meta-analysis
      and in another meta-analysis, both of which showed no difference in the incidence
      of cancer in ARB treatment groups relative to control groups. The US Food and
      Drug Administration has recently asserted that evidence does not support an
      association between ARBs and the development of cancer. The current review
      compares the 3 published meta-analyses assessing the association between ARBs and
      cancer and shows that outcome reporting bias contributed to the conflicting
      results. Given the prevalence of this form of bias in the scientific literature,
      the processes for systematic reviews and meta-analyses are under siege, and there
      is an important role for health care regulators to play. If all outcome data from
      clinical trials were to be reported in the public domain, independent analyses
      could be performed and the results of industry-sponsored trials verified.
      Furthermore, if regulators were to mandate the publication, in the public domain,
      of all clinical outcomes collected in clinical trials, outcome reporting bias
      could be eliminated.

PMID- 23129870
TI  - Practice spotlight: pharmacist practice in rural Saskatchewan.

PMID- 23129869
TI  - Implementation of a near-peer teaching model in pharmacy education: experiences
      and challenges.

PMID- 23129871
TI  - Should direct thrombin inhibitors replace warfarin for prophylaxis of
      thromboembolism in canadians with atrial fibrillation?

PMID- 23129872
TI  - Drug shortages: what does france do better than Canada?

PMID- 23129873
TI  - Additional thoughts on drug shortages.

PMID- 23129874
TI  - Bar coding-not just in the supermarket anymore.

PMID- 23129875
TI  - Premarital Cohabitation and Marital Dissolution: An Examination of Recent
      Marriages.
AB  - An ongoing question remains for family researchers: Why does a positive
      association between cohabitation and marital dissolution exist when one of the
      primary reasons to cohabit is to test relationship compatibility? Drawing on
      recently collected data from the 2006 - 2008 National Survey of Family Growth,
      the authors examined whether premarital cohabitation experiences were associated
      with marital instability among a recent contemporary (married since 1996)
      marriage cohort of men (N = 1,483) and women (N = 2,003). They found that a
      dichotomous indicator of premarital cohabitation was in fact not associated with
      marital instability among women and men. Furthermore, among cohabitors, marital
      commitment prior to cohabitation (engagement or definite plans for marriage) was
      tied to lower hazards of marital instability among women, but not men. This
      research contributes to our understanding of cohabitation, marital instability,
      and broader family change.

PMID- 23129876
TI  - Suicide Risk at Young Adulthood: Continuities and Discontinuities From
      Adolescence.
AB  - Young adult suicide is an important social problem, yet little is known about how
      risk for young adult suicide develops from earlier life stages. In this study the
      authors report on 759 young adults who were potential high school dropouts as
      youth. At both adolescence and young adulthood, measures of suicide risk status
      and related suicide risk factors are collected. With a two-by-two classification
      on the basis of suicide risk status at both adolescence and young adulthood, the
      authors distinguish four mutually exclusive groups reflecting suicide risk at two
      life stages. Using ANOVA and logistic regression, both adolescent and young adult
      suicide risk factors are identified, with evidence of similarity between risk
      factors at adolescence and at young adulthood, for both individual-level and
      social-context factors. There is also support for both continuity and
      discontinuity of adolescent suicide risk. Implications for social policy are
      discussed.

PMID- 23129877
TI  - Revisiting the hierarchy of urban areas in the Brazilian Amazon: a multilevel
      approach.
AB  - The Legal Brazilian Amazon, while the largest rainforest in the world, is also a
      region where most residents are urban. Despite close linkages between rural and
      urban processes in the region, rural areas have been the predominant focus of
      Amazon-based population-environment scholarship. Offering a focus on urban areas
      within the Brazilian Amazon, this paper examines the emergence of urban
      hierarchies within the region. Using a combination of nationally representative
      data and community based surveys, applied to a multivariate cluster methodology
      (Grade of Membership), we observe the emergence of sub-regional urban networks
      characterized by economic and political inter-dependency, population movement,
      and provision of services. These networks link rural areas, small towns, and
      medium and large cities. We also identify the emergence of medium-size cities as
      important nodes at a sub-regional level. In all, the work provides insight on the
      proposed model of 'disarticulated urbanization' within the Amazon by calling
      attention to the increasing role of regional and sub-regional urban networks in
      shaping the future expansion of land use and population distribution in the
      Amazon. We conclude with a discussion of implications for increasing intra
      regional connectivity and fragmentation of conservation areas and ecosystems in
      the region.

PMID- 23129878
TI  - Out-migration and land-use change in agricultural frontiers: insights from
      Altamira settlement project.
AB  - One of Daniel Hogan's lasting impacts on international demography community comes
      through his advocacy for studying bidirectional relationships between environment
      and demography, particularly migration. We build on his holistic approach to
      mobility and examine dynamic changes in land use and migration among small farm
      families in Altamira, Para, Brazil. We find that prior area in either pasture or
      perennials promotes out-migration of adult children, but that out-migration is
      not directly associated with land-use change. In contrast to early formulations
      of household life cycle models that argued that aging parents would decrease
      productive land use as children left the farm, we find no effect of out-migration
      of adult children on land-use change. Instead, remittances facilitate increases
      in area in perennials, a slower to pay off investment that requires scarce
      capital, but in pasture. While remittances are rare, they appear to permit sound
      investments in the rural milieu and thus to slow rural exodus and the potential
      consolidation of land into large holdings. We would do well to promote the
      conditions that allow them to be sent and to be used productively to keep
      families on the land to avoid the specter of extensive deforestation for pasture
      followed by land consolidation.

PMID- 23129879
TI  - Verbal Play as an Interactional Discourse Resource in Early Stage Alzheimer's
      Disease.
AB  - BACKGROUND: Verbal play, the creative and playful use of language to make puns,
      rhyme words, and tease, is a pervasive and enjoyable component of social
      communication and serves important interpersonal functions. The current study
      examines the use of verbal play in the communicative interactions of individuals
      with Alzheimer's disease as part of a broader program of research on language-and
      memory-in-use.  AIMS: To document the frequency of verbal play in the
      communicative interactions of individuals with very mild Alzheimer's disease (AD)
      and their familiar communication partners. To characterize the interactional
      forms, resources, and functions of playful episodes.  METHODS: Using quantitative
      group comparisons and detailed discourse analysis, we analyzed verbal play in the
      interactional discourse of five participants with very mild AD and five healthy
      (demographically matched) comparison participants. Each participant interacted
      with a familiar partner while completing a collaborative referencing task, and
      with a researcher between task trials.  RESULTS: A total of 1,098 verbal play
      episodes were coded. Despite being in the early stages of AD, all the AD
      participants used verbal play. There were no significant group differences in the
      frequency of verbal play episodes or in the interactional forms, resources, or
      functions of those playful episodes between AD and healthy comparison pair
      sessions.  CONCLUSIONS: The successful use of verbal play in the interactions of
      individuals with very mild AD and their partners highlights an area of preserved
      social communication. These findings represent an important step, both clinically
      and for research, in documenting the rich ways that individuals with early stage
      AD orchestrate interactionally meaningful communication with their partners
      through the use of interactional discourse resources like verbal play. This work
      also offers a promising clinical tool for tracking and targeting verbal play
      across disease progression.

PMID- 23129880
TI  - Natural Conversations as a Source of False Memories in Children: Implications for
      the Testimony of Young Witnesses.
AB  - Research on factors that can affect the accuracy of children's autobiographical
      remembering has important implications for understanding the abilities of young
      witnesses to provide legal testimony. In this article, we review our own recent
      research on one factor that has much potential to induce errors in children's
      event recall, namely natural memory sharing conversations with peers and parents.
      Our studies provide compelling evidence that not only can the content of
      conversations about the past intrude into later memory but that such exchanges
      can prompt the generation of entirely false narratives that are more detailed
      than true accounts of experienced events. Further, our work show that deeper and
      more creative participation in memory sharing dialogues can boost the damaging
      effects of conversationally conveyed misinformation. Implications of this
      collection of findings for children's testimony are discussed.

PMID- 23129881
TI  - Journal of parasitic diseases reinvigorated.

PMID- 23129882
TI  - A review of the complexity of biology of lymphatic filarial parasites.
AB  - There are about five more common, including Wuchereria bancrofti and Brugia
      malayi, and four less common filarial parasites infecting human. Genetic analysis
      of W. bancrofti populations in India showed that two strains of the species are
      prevalent in the country. The adult filarial parasites are tissue specific in the
      human host and their embryonic stage, called microfilariae (mf), are found in the
      blood or skin of the host, depending upon the species of the parasite. Three
      genetically determined physiological races exist in W. bancrofti and B. malayi,
      based on the microfilarial periodicity. They are the nocturnally periodic,
      nocturnally subperiodic and diurnally subperiodic forms. The susceptibility of a
      mosquito species to filarial infection depends on various factors, which could be
      genetic, physiological or physical. Survival analysis of Culex quinquefasciatus
      infected with W. bancrofti showed that the parasite load in the mosquito is a
      risk factor of vector survival. The extrinsic life cycle of the parasite is
      initiated when the mf are ingested by a mosquito vector during feeding on the
      host blood. On maturity, most of the infective L3 stage larvae migrate to the
      head and proboscis of the mosquito to get transmitted to the mammalian host
      during subsequent feeding. They develop to the adult L5 stage and the period of
      development and the longevity of the parasites varies according to the species of
      the nematode and the mammalian host. The rate of production of mf by the adult
      female was found to be stable at least for a period of five years. The life span
      of the mf has some influence on the dynamics of transmission of filariasis.
      Recent studies show that the endosymbiont, Wolbachia, plays an important role in
      the survival of filarial parasites. The possibility of in vitro and in vivo
      culture of filarial parasites is also reviewed.

PMID- 23129883
TI  - Malaria transmission and disease burden in Assam: challenges and opportunities.
AB  - Malaria is major public health illness in Assam and 30-40% of the population is
      estimated to be at high-risk. Despite decades of attempted control interventions,
      malaria transmission is perennial and persistent in most parts of the state
      mostly transmitted by Anopheles minimus. Malaria outbreaks are returning
      associated with high rise in Plasmodium falciparum and attributable death cases.
      Therapeutic efficacy investigations for treatment of malaria revealed that
      chloroquine resistance was widespread for which artemisinin-based combination
      therapy (ACT) is being instituted in the control program. For data based on the
      preceding years, we briefly reviewed the available information on transmission
      dynamics, vector biology and control, drug policy, and discuss the challenges and
      opportunities for strengthening interventions for malaria control to help design
      situation specific strategies to check impending disease outbreaks with special
      reference to Assam. Under increased assistance from external agencies, we
      strongly advocate scaling up interventions based on mass distribution of long
      lasting insecticidal nets (LLINs) for prevention and ACTs for treatment of drug
      resistant malaria, and developing strong health delivery system in high-risk
      areas for meeting the complex emergencies and achieving transmission reduction.

PMID- 23129884
TI  - Emergence periodicity of Phlebotomus argentipes annandale and brunetti (Diptera:
      psychodidae): A laboratory study.
AB  - Phlebotomus argentipes Annandale and Brunetti (Diptera: Psychodidae) is the
      vector for visceral leishmaniasis in India. The aspects of its biology such as
      feeding and man vector contact are associated with emergence periodicity of the
      adult. Hence, the present study was made to find out the actual emergence period
      of P. argentipes. Wild caught P. argentipes were confined in the rearing pots
      inside laboratory. The newly emerged adults were collected at hourly intervals
      and released in to separate polythene bags and were held at 4 degrees C till
      death. Sand flies were segregated sex-wise after the death under a microscope.
      The emergence of adult was observed throughout the day. However, the male
      preferred dawn emergence and the female the dusk. Two peaks of emergence were
      found in a day; first one in the morning (0900h) and the second one in the
      evening (1800h). The ratio of both sexes was found to be about equal. The
      emergence of adult was found to be 77% out of total eggs laid, which was
      completed within 7-10 days from the 1st day of emergence under laboratory
      conditions (25 degrees C to 31 degrees C and 70% to 75% relative humidity). This
      study has important bearings to find out the actual time for personal protection
      against biting of sand flies to prevent the transmission of Kala-azar.

PMID- 23129885
TI  - Helminth parasite spectrum in rodent hosts from bamboo growing areas of Mizoram,
      North-east India.
AB  - In the northeastern state of Mizoram, India the rodent outbreak is periodic and
      coincides with bamboo (Melocanna baccifera) bloom causing a tremendous
      destruction to food crops that often results in famine. The present study was
      undertaken during the bamboo flowering period (2006-2008) to assess the parasite
      spectrum and load in the bourgeoning rodent population of the affected region.
      The survey results of the populations of 9 prevalent rodent species revealed that
      nematodes were the most dominant parasitic group followed by cestodes of the
      order Cyclophyllidea; however, the trematodes were found to be conspicuously
      missing. The nematodes harbored by the rodents belonged to the genera: Syphacia,
      Aspicularis, Trichuris, Rictularia, Capillaria, Trichosomoides, Nippostrongylus,
      Hepatojarakus and Heterakis, whereas the cestode genera included Hymenolepis,
      Raillietina and Taenia. Hymenolepis diminuta was the commonly encountered
      species. Only one acanthocephalan (Moniliformis sp.) could be collected during
      the entire study.

PMID- 23129886
TI  - Effect of isometamidium hydrochloride on Trypanosoma evansi infections in rats.
AB  - Effect of Isometamidium treatment of rats infected with Trypanosoma evansi was
      studied under experimental condition. The infection resulted in 100 per cent
      mortality by 7 day post treatment (DPT) in the infected untreated rats (Gr.II)
      and Isometamidium-HCl exerted 90 percent anti-trypanosomal efficacy.
      Haematological studies of all the groups on 3 day post infection (DPI) and on 7
      DPT showed that T. evansi infection significantly decreased haematological
      values, however Isometamidium treatment significantly (P < 0.05) improved Hb and
      PCV without any significant changes in TEC and TLC values. Serum AST and ALT
      activities were significantly (P < 0.01) higher in the treated rats compared to
      healthy rats. Treatment with Isometamidium-HCl significantly improved blood
      glucose level but decreased creatinine level compared to pretreatment values.
      There was no significant change in BUN level of treated rats but the value was
      higher (P < 0.01) compared to healthy rats.

PMID- 23129887
TI  - Therapeutic efficacy of Zanthoxylum rhetsa DC extract against experimental
      Hymenolepis diminuta (Cestoda) infections in rats.
AB  - Zanthoxylum rhetsa DC (Rutaceae), commonly called prickly ash, is used in the
      folk medicine of Naga tribes in India as a deworming remedy. In the present
      study, the therapeutic efficacy of Z. rhetsa leaf extract was investigated
      against experimental Hymenolepis diminuta (Cestoda) infections in albino rats.
      The efficacy of extract was determined on the basis of reduction in the eggs per
      gram of feces (EPG) counts and worm load following treatment with 100, 200, 400
      and 800 mg/kg, p.o. doses of plant extract. For comparison's sake, animals were
      also treated with a reference drug, praziquantel at 5 and 25 mg/kg body weight
      doses. Three treatment regimes were followed to monitor the effects of extract on
      cestode parasite: (1) Treatment on day 2-4 postinoculation (pi) of cysticercoids
      against the larval stages; (2) treatment on day 8-10 pi against the immature
      stages; and (3) treatment on day 21-25 pi against the adult stages of parasite.
      The extract revealed its maximum efficacy against the larval stage, where its 800
      mg/kg dose showed a worm count reduction of 86.60%, compared to 80.00% by the
      reference drug, praziquantel (5 mg/kg dose). The EPG counts also decreased
      drastically from 23,389 +/- 2,372 to 0 in the same treatment group, compared to
      33,161 +/- 1,383 recorded in the control group. The efficacy of extract was found
      to be of moderate level against the immature and adult stages of parasite. The
      present investigation holds the evidence that the leaves of Z. rhetsa possess
      significant anticestodal property and supports its use in folk medicine.

PMID- 23129888
TI  - Anthelmintic efficacy of ethanolic shoot extract of Alpinia nigra on tegumental
      enzymes of Fasciolopsis buski, a giant intestinal parasite.
AB  - Ethanolic shoot extract of Alpinia nigra, a traditionally used anthelmintic
      medicinal plant among the Tripuri tribes of north-east India, was tested in vitro
      to determine its anthelmintic efficacy in gastrointestinal trematode Fasciolopsis
      buski, using alterations in the activity of vital tegumental enzymes viz. acid
      phosphatase (AcPase), alkaline phosphatase (AlkPase) and adenosine triphosphatase
      (ATPase). Live adult F. buski treated in vitro with different concentrations of
      the plant extract showed significant decline in the visible stain histochemically
      and enzyme activities. Quantitatively, the total enzyme activity of AcPase,
      AlkPase and ATPase was found to be reduced by 45, 41 and 43%, respectively
      compared to the control. The reference drug, praziquantel also showed more or
      less similar effect like that of the plant extract. The results suggest that the
      tegumental enzymes of the parasite may be an important target of action for
      active component(s) of A. nigra, which appears to act transtegumentally.

PMID- 23129889
TI  - Treatment of dairy buffaloes naturally infected with sarcoptic mange.
AB  - Therapeutic trials of sarcoptic mange in buffaloes were studied at local
      Livestock farms, Lahore (Pakistan). A total of 600 buffaloes were examined over 1
      year period (August 2006 to July 2007) for prevalence study, while 60 buffaloes
      were selected for therapeutic trial. Sarcoptic mange was recorded in 66 (11%)
      animals. The highest monthly prevalence was reported during the months of January
      and February (18%) followed by December and March (16%) whereas lowest during the
      month of July (2%). Over all highest seasonally prevalence was recorded during
      winter (16.5%) and lowest during summer (5%). Moreover, highest infestation rate
      was recorded among young (<3 months) buffaloes than with age >3 months. Sex-wise
      prevalence indicated more prevalence in buffalo bulls (13.15%) than female
      buffaloes (9.28%). Therapeutic trials were carried out by using ivermectin,
      doramectin and trichlorphon as per manufacturer's recommendations for a period of
      10 days, while one group was kept as untreated control. Negative skin scraping,
      disappearance of gross lesions, stoppage of itching and regrowth of normal hair
      were taken as the criterion to assess the efficacy of these drugs.

PMID- 23129890
TI  - Characterization of the glutamate dehydrogenase activity of Gigantocotyle
      explanatum and Gastrothylax crumenifer (Trematoda: Digenea).
AB  - Glutamate dehydrogenase (GLDH) (EC 1.4.1.3) is a ubiquitous enzyme, which is
      present at the protein and carbohydrate metabolism crossroads. The enzyme
      activity was investigated in biliary and rumen amphistomes, Gigantocotyle
      explanatum and Gastrothylax crumenifer, respectively, infecting the Indian water
      buffalo Bubalus bubalis. The enzyme activity was consistently higher in G.
      explanatum as compared to G. crumenifer, where NAD(H) was utilized as coenzyme
      and the pH optima was recorded at 8. The K(m) and V(max) values for alpha
      ketoglutarate were 2.1 mM and 9.09 units in G. explanatum, whereas 3.03 mM and
      1.90 units in G. crumenifer, respectively. Among the allosteric modulator
      nucleotides, AMP, ADP, ATP, GMP, CMP and UMP, only AMP enhanced GLDH activity in
      G. crumenifer while ADP was stimulatory in G. explanatum. The amino acid leucine
      stimulated the GLDH activity in both the amphistomes while alanine was
      stimulatory only in G. crumenifer. Pronounced interspecific differences in
      response to different metabolic inhibitors like diethyldithiocarbamate,
      semicarbazide hydrochloride and mercurial ions were also observed. The osmotic
      stress alters the enzyme activity, particularly in hypertonic saline the GLDH
      activity increased significantly (p < 0.01) in G. explanatum, while insignificant
      effects were observed in rumen dwelling G. crumenifer. Histoenzymology revealed
      region/tissue specific distribution of GLDH with prominent staining in tissues
      like vitellaria, lymph system and tegument/subtegument, thus showing specific
      distribution of GLDH indicating differential metabolic state. Such intergeneric
      differences in GLDH activity could also be a consequence of occupying different
      microenvironments within the same host.

PMID- 23129891
TI  - Histopathological changes of the esophagus of the freshwater eels, Macrognathus
      aculeatus (Bl.) and Mastacembelus pancalus (Lac.) due to infection of
      metacercariae of Clinostomum mastacembeli Jaiswal, 1957.
AB  - Macrognathus aculeatus (Bl.) and Mastacembelus pancalus (Lac.) (Family:
      Mastacembelidae) are considered to be the most delicious fish in Andhra Pradesh
      due to the tenderness of their muscles. The metacercariae of Clinostomum
      mastacembeli Jaiswal, 1957 are found infesting the oesophagus of these fishes
      heavily. During present studies, histopathological changes caused due to the
      encystment of metacercariae of C. mastacembeli in the oesophagus of these fishes
      were observed. The four layers of the oesophagus namely; serosa, muscualris
      layer, submucosa and mucosa were found severely affected. Histopathological
      changes included decrease in the lumen diameter of the oesophagus, atrophy and
      necrosis of epithelial cells of serosa layer, shrinkage of villi due to
      thickening of muscularis layer and formation of small vacuoles in the sub-mucosal
      layers.

PMID- 23129892
TI  - Standardization and application of indirect plate ELISA for immunodiagnosis of
      paramphistomosis in ruminants.
AB  - Indirect plate enzyme-linked immunosorbent assay was standardized and evaluated
      for its effectiveness in immunodiagnosis of paramphistomosis in experimental and
      clinical cases in sheep, goat, cattle and buffaloes by using somatic whole adult
      antigen of Paramphistomum epiclitum and Gastrothylax crumenifer. Plate
      enzymelinked immunosorbent assay (ELISA) was standardized using 2 MUg/ml of
      antigen concentration with 1:200 and 1:1,000 of sera and conjugate dilution.
      Indirect Plate ELISA was able to demonstrate the antibody titre at different
      weeks postinfection in experimental sheep. Immune response at weekly interval
      varied in all the four experimental sheep. A paired t-test between two types of
      somatic antigens (P. epiclitum and G. crumenifer) showed that experimental sheep
      sera showed more affinity for homologous antigen as compared to heterologous
      antigen. A comparison of plate ELISA on suspected field sera and fecal samples
      examination by sedimentation method revealed that 77 samples were found to be
      positive by ELISA but only seven by fecal examination. Sensitivity of plate ELISA
      was found to be 85.71%, whereas specificity was 23.65% indicating that this test
      is quite sensitive for clinical cases; an early diagnosis, however, lacks
      specificity. In comparison to ELISA test the sensitivity and specificity of fecal
      examination were 7.79 and 88%, respectively.

PMID- 23129893
TI  - Metazoan parasites of Mystus vittatus (Bloch) of River Godavari with description
      of a new species of Acanthocephala, Raosentis godavarensis sp. nov.
AB  - A total of 9 metazoan parasitic species were identified from Mystus vittatus
      (Bloch) in river Godavari during 2005-2007 including 2 monogeneans, 2 digeneans,
      3 acanthocephalans and 2 copepods. Two species of monogeneans (Bifurcohaptor
      indicus and Thaparocleidus tengra), digeneans (Haplorchoides macrones and
      metacercariae of Isoparorchis hypselobagri), an acanthocephalan (Raosentis
      podderi) found during the present study are of common occurrence in this fish. M.
      vittatus constitutes a new host record for an acanthocephalan, Raosentis thapari
      and 2 copepods, Argulus striatus and Lamproglena hospetensis. The occurrence of
      A. striatus represents unusual for M. vittatus. A new species of acanthocephala,
      Raosentis godavarensis sp. nov is reported, described and illustrated.

PMID- 23129894
TI  - Indoor resting density pattern of mosquito species in Fingeswar block of Raipur
      district in Chhattisgarh, central India.
AB  - Anopheline mosquitoes are vectors of human malaria and hence they are of greatest
      concern. Around 40% of the world's population resides in malaria affected areas.
      Malaria affects poor communities and causes enormous economic losses. The deadly
      disease annually causes clinical illness in 400-600 million people and kills 2-3
      millions annually (WHO 2008). Faunistic survey was conducted in Fingeswar block
      in Raipur district of Chhattisgarh state of India during January 2003 to March
      2004 to asses the prevalence of different species of mosquitoes and their
      seasonal variations.Indoor resting mosquitoes were collected from selected houses
      in 5 villages using aspirator tube and torch light in the morning between 06:00
      08:00. Adult mosquitoes were identified using standard morphological and
      pictorial keys following Rao (1984), Das et al. (1991) and Reuben et al. (1994)
      and assessed as person hour density.A total of 13,248 mosquitoes were collected
      during the study period. Nine species of mosquitoes comprising of 4 genera with 5
      Anopheles, two Culex and one each Armigeres and Aedes were recorded. The malaria
      vectors constituted 14.09% of the total mosquito collections. Anopheles subpictus
      (25.81%) showed the dominance followed by A. annularis (8.68%), A. barbirostris
      (6.76%), A. culicifacies (5.41%) and A. pallidus (4.11%). The other genus
      recorded included Culex quinquefasciatus (38.38%), C. vishnui (3.32%), Armigeres
      subalbatus (6.92%) and Aedes albopictus (0.29%). The density of all the species
      were high in months of August, September and October, decreased in month of May
      and June 2003. There was a significant (p < 0.01) positive correlation between
      temperature and density of A. culicifacies and A. annularis. The seasonal
      distribution pattern of A. culicifacies (primary) and A. annularis (secondary)
      malaria vectors along with other mosquito species was studied which is an
      important component of epidemiological study of malaria. This information will
      help in formulating a baseline structure for control program in the study region.

PMID- 23129895
TI  - A survey of phthirapteran ectoparasites on the Grey Francolin, Francolinus
      Pondicerianus (Galliformes: phasianidae) in North-India.
AB  - As many as 144 brown francolin (Francolinus pondicerianus) were netted from 6
      sites of Uttarakhand during the period from October, 2006 to September, 2008, to
      note the occurrence of phthirapteran species. Out of 144 birds, 45.83% were found
      to be infested with two species of lice i.e. Menacanthus kalatitar and Goniocotes
      jirufi, the former species occurring in 29.17% of birds (mean intensity 11.45 and
      sample mean abundance 3.34) whereas the later infesting only 25.69% of birds
      (mean intensity 8.22 and sample mean abundance 2.11). Significant positive
      correlation existed between mean monthly lice index and mean monthly temperature
      as well as photoperiod, while negative correlation was seen with respect to
      relative humidity and rainfall.

PMID- 23129896
TI  - Evolution of an idea: The case of prophylaxis against infective endocarditis.

PMID- 23129897
TI  - Prognostic value of clinical and Doppler echocardiographic findings in children
      and adolescents with significant rheumatic valvular disease.
AB  - INTRODUCTION: The diagnosis of acute rheumatic fever (RF) is based on clinical
      findings. However, during the chronic phase of the disease, the clinical approach
      is not sufficient for the follow-up of the patients and the Doppler
      echocardiography is a tool for the diagnosis of cardiac involvement. Prognostic
      variables that influence long-term outcomes are not well known. METHODS: 462
      patients with RF according to Jones criteria were studied, and followed-up from
      the initial attack to 13.6 +/- 4.6 years. All patients underwent clinical
      assessment and Doppler echocardiography for the detection of heart valve
      involvement in the acute and chronic phases. Multivariate logistic regression
      analysis was used to identify the factors influencing long-term heart valve
      disease. RESULTS: Carditis occurred in 55.8% and subclinical valvulitis in 35.3%
      patients. In the chronic phase, 33% of the patients had significant valvular
      heart disease. No normal Doppler echocardiography exam was observed on patients
      who had severe valvulitis, although heart auscultation had become normal in 13%
      of these. In the multivariate analysis, only the severity of carditis and the
      mitral and/or aortic valvulitis were associated with significant valvular heart
      disease. Chorea or arthritis were protective factors for significant valvular
      heart disease, odds ratio 0.41 (95% C.I. 0.22 - 0.77) and 0.43 (95% C.I. 0.23 -
      0.82), respectively. CONCLUSIONS: Our study suggests that the use of Doppler
      echocardiography during RF helps to identify prognostic factors regarding the
      development of significant valvular heart disease. Initial severe carditis is an
      important factor in the long-term prognosis of chronic RHD, whereas arthritis and
      chore during the initial episode of RF appears to be protective. Strict secondary
      prophylaxis should be mandatory in high risk patients.

PMID- 23129898
TI  - Diagnosis of acute rheumatic carditis: An echo in time....

PMID- 23129899
TI  - Cardiac involvement in Kawasaki disease in Pakistani children.
AB  - INTRODUCTION: Coronary artery involvement is the most dreaded long-term
      complication of Kawasaki disease. Our aim was to look at the pattern of
      cardiovascular involvement in Pakistani children admitted with Kawasaki disease.
      METHODS: This study included children admitted with Kawasaki disease at the Aga
      Khan University Hospital Karachi over a period of 14 years from January 1997 to
      December 2010. Information gathered included patient demographics, clinical
      features, investigations, echocardiographic findings, treatment and follow-up.
      Those with coronary artery involvement on initial echocardiogram remained on long
      term follow-up with clinical examination and echocardiogram. RESULTS: A total of
      56 patients were admitted. (Mean age at diagnosis 33 +/- 30 months, age range 2
      months to 9 years). 18% of patients had incomplete features. Twenty-five percent
      (14/56) patients presented after 10 days of fever. Cardiac examination was normal
      except for tachycardia. Abnormal coronary arteries were seen in 23 patients (41%)
      - left main coronary artery in 23 (41%), left anterior descending and right main
      coronary artery in 20 (36%), circumflex branch in 17 (30%). Risk factors for
      cardiac involvement were male sex, fever >10 days duration at the time of initial
      presentation and neutrophil percentage >75% in the initial white blood cell
      counts. Fifty four of 56 cases received intravenous immunoglobulin (IVIG),
      Seventy-five percent of the patients received IVIG within 10 days of illness.
      Mean duration of follow-up was 2.5 years. Eight percent of the patients still
      continue to have abnormal coronaries. There was no mortality. CONCLUSIONS: A
      higher incidence of coronary artery involvement was found in our study.
      Presentation after 10 days of illness increases the risk of coronary artery
      involvement. High index of suspicion among the general pediatricians about the
      disease can possibly be helpful for early referral and treatment.

PMID- 23129900
TI  - Finding Kawasaki disease.

PMID- 23129901
TI  - Transcatheter closure of large patent ductus arteriosus with severe pulmonary
      arterial hypertension: Short and intermediate term results.
AB  - OBJECTIVE: To assess the efficacy and safety of transcatheter closure (TCC) of
      patent ductus arteriosus (PDA) with severe pulmonary arterial hypertension (PHT).
      BACKGROUND: TCC of small and moderate-sized PDAs is well established. However,
      there is a paucity of data on TCC of large PDA with severe PHT. METHODS: This is
      a retrospective observational study of 76 patients with large PDA and severe PHT
      who were referred for TCC. Multiple clinical and investigational parameters were
      evaluated to decide the reversibility of PHT. Following the TCC, patients were
      serially followed up to assess the efficacy and safety of closure and its impact
      on PHT. RESULTS: Of 76 patients, nine were found to have PDA with Eisenmenger's
      syndrome. Of remaining 67, two were thought to have irreversible PHT based on
      hemodynamic data obtained after balloon occlusion of the duct. Sixty five
      patients, who eventually underwent TCC of PDA, had a median age of 9.1 years
      (range 1 month to 40 years). The weight ranged between 2.5 to 62 kg (median 14
      kg). The PDA size was 9.1 +/- 4.6 mm. The mean systolic pulmonary artery pressure
      was 66.9 +/- 15.3 mm Hg. Duct occluder was used in 63 and muscular ventricular
      septal defect closure device in 2. The follow up was available in 56 (86%) with a
      mean follow up period of 65 +/- 34 months. All the patients had complete closure
      of the PDA at 6 months follow up. Mild obstruction of left pulmonary artery (n=3)
      and aortic isthmus flow (n=6) was noted at the time of discharge. During the
      follow up, partial or complete resolution of PHT was observed in all the patients
      in whom Doppler-derived right ventricular systolic pressure was recorded
      (available in 40 of 56 patients). CONCLUSIONS: TCC of large PDA with severe PHT
      and significant left to right shunt was found to be effective and safe in the
      short and intermediate term.

PMID- 23129902
TI  - Large patent ductus arteriosus: To close or not to close.

PMID- 23129903
TI  - Palliative stent implantation for coarctation in neonates and young infants.
AB  - BACKGROUND: In selected neonates and infants, primary palliative stent
      implantation may be indicated for coarctation of the aorta. We describe our
      experience with this approach in five consecutive patients. METHODS: Five
      neonates and infants (age range 6 to 68 days, gestation 33 to 38 weeks, weight
      range at procedure of between 1650 to 4000 g) underwent palliative stent
      implantation as primary therapy for coarctation of the aorta. Indications for
      primary stent implantation were varied. All procedures were performed by elective
      surgical cut down of the axillary artery. Standard coronary stents (diameter 4.5
      to 5 mm, length 12 to 16 mm) were delivered via a 4F sheath. The axillary artery
      was repaired after removal of the sheath. RESULTS: All procedures were acutely
      successful, and without procedural complications. All patients survived to
      hospital discharge. Four patients have subsequently undergone elective stent
      removal and surgical repair of the arch, at between 38 and 83 days following
      stent implantation. Complete stent removal was achieved in three patients. Over a
      follow-up ranging between 8 weeks and 36 months, none of the patients has had any
      further complications. CONCLUSIONS: This palliative approach is warranted in
      carefully selected patients. Long-term follow-up is required.

PMID- 23129904
TI  - Effect of ventricular size and function on exercise performance and the
      electrocardiogram in repaired tetralogy of Fallot with pure pulmonary
      regurgitation.
AB  - BACKGROUND: In repaired tetralogy of Fallot (TOF), exercise test parameters like
      peak oxygen uptake and ventilatory efficiency predict mortality. Studies have
      also suggested cardiac magnetic resonance (CMR)-derived right ventricular (RV)
      size threshold values for pulmonary valve replacement in repaired TOF. However,
      effects of proposed RV size on exercise capacity and morbidity are not known.
      METHODS: The relationship between CMR-derived ventricular size, function, and
      pulmonary regurgitation (PR) and NYHA class, exercise performance, and
      electrocardiogram (ECG) was studied in patients of repaired TOF with pure PR in a
      retrospective review of records. RESULTS: 46 patients (22 females), mean age 14
      years (8-30.8), were studied. There was no relationship between CMR-derived
      ventricular size, function, or PR and exercise test parameters, or NYHA class. RV
      end systolic and end diastolic volume correlated positively with the degree of
      PR. QRS duration on ECG correlated positively with RV end-diastolic volume (P <
      0.01, r(2) = 0.34) and PR (P < 0.01, r(2) = 0.52). CONCLUSIONS: In repaired TOF
      and pure PR, there is no correlation between ventricular size or function and
      exercise performance. RV size increases with increasing PR. Timing of pulmonary
      valve replacement in TOF with pure PR needs further prospective evaluation for
      its effect on morbidity and mortality.

PMID- 23129905
TI  - Awareness of fetal echo in Indian scenario.
AB  - BACKGROUND: Fetal echocardiography is a well established sensitive tool to
      diagnose congenital heart disease (CHD) in utero. One of the determinants of
      effective utilization of fetal echocardiography is its awareness in the general
      population. The present hospital based study was undertaken to assess the
      awareness of the need for fetal echocardiography amongst Indian parents. METHODS:
      One thousand one hundred and thirty eight consecutive parents who visited the
      pediatric cardiology outpatient department of a tertiary care centre over a
      period of two months were asked to fill up a questionnaire that included their
      demographic data, educational status, history of CHD in children, awareness of
      fetal echocardiography and source of information and timing of fetal
      echocardiogram if performed. The data was categorized and awareness was noted in
      different groups. RESULTS: The awareness in the study population was 2.2%.
      Awareness was found to be similar across the study population irrespective of the
      demographics and high risk status of the parents. CONCLUSIONS: The awareness of
      fetal echocardiography, an important tool in reducing the incidence of complex
      CHD, thereby impacting public health, is alarmingly low in the population
      studied. Appropriate action to increase awareness of fetal echocardiography needs
      to be looked into.

PMID- 23129906
TI  - Endothelial dysfunction and atherosclerosis in children with irreversible
      pulmonary hypertension due to congenital heart disease.
AB  - OBJECTIVE: To assess endothelial dysfunction and the risk for coronary
      atherosclerosis in children with irreversible pulmonary hypertension due to
      congenital heart disease (CHD). METHODS: The study included 18 cyanotic patients
      (the mean age was 12.28 +/- 3.26 years) who developed irreversible pulmonary
      hypertension due to cyanotic and acyanotic CHDs, and 18 control patients (the
      mean age was 11.78 +/- 3.00 years). Study groups were compared for flow-mediated
      dilatation (FMD), carotid intima media thickness (CIMT) and atherosclerotic risk
      factors. RESULTS: Compared to the control group, the mean FMD was significantly
      reduced in the cyanotic group (5.26 +/- 2.42% and 9.48 +/- 2.60%, respectively; P
      value < 0.001). No significant difference was observed between the groups in CIMT
      (0.41 +/- 0.08 mm and 0.39 +/- 0.06 mm, respectively; P-value = 0.299). The
      levels of total cholesterol, low-density lipoprotein-cholesterol and very low
      density lipoprotein-cholesterol were statistically significantly lower compared
      tothe control group (P-value = 0.001, 0.006 and 0.014, respectively), whereas no
      statistically significant difference was found in the levels of high-density
      lipoprotein-cholesterol and triglycerides (P-value = 0.113 and 0.975,
      respectively). CONCLUSIONS: Systemic endothelial dysfunction in children with
      irreversible pulmonary hypertension due to CHD was noted but there was no
      increased risk for atherosclerosis.

PMID- 23129907
TI  - Safety and usefulness of outreach clinic conducted by pediatric echosonographers.
AB  - BACKGROUND: Outreach echocardiographic services led by cardiac sonographers may
      help district level hospitals in the management of patients suspected to have
      cardiac anomalies. However, the safety and utility of such an approach is not
      tested. METHODS: We retrospectively reviewed our experience of patients seen in
      the outreach visits by the echocardiographers alone and subsequently reviewed in
      the pediatric cardiology clinic. Comparison between the diagnosis made by the
      echocardiographer and the consultant pediatric cardiologist were done. We defined
      safety as no change in patient management plan between the outreach evaluation
      and the pediatric cardiology clinic evaluation, and we defined usefulness as
      being beneficial, serviceable and of practical use. RESULTS: Two senior
      echocardiographic technicians did 41 clinic visits and over a period of 17
      months, 623 patients were seen. Patients less than 3 months of age constitute 63%
      of the total patients seen. Normal echocardiographic examinations were found in
      342 (55%) of patients. These patients were not seen in our cardiology clinic.
      Abnormal echocardiographic examinations were found in 281 (45%) of patients.
      Among the 281 patients with abnormal echos in the outreach visits, 251 patients
      (89.3%) were seen in the pediatric cardiology clinic. Comparing the results of
      the outreach clinic evaluation to that of the pediatric cardiology clinic, 73
      patients (29%) diagnosed to have a minor CHD turned to have normal
      echocardiographic examinations. In all patients seen in both the outreach clinics
      and the pediatric tertiary cardiac clinics there was no change in patient's
      management plan. CONCLUSIONS: Outreach clinic conducted by pediatric echo
      sonographers could be useful and safe. It may help in reducing unnecessary visits
      to pediatric cardiology clinics, provide parental reassurance, and help in
      narrowing the differential diagnosis in critically ill patient unable to be
      transferred to tertiary cardiac centers provided it is done by experienced
      echosonographers.

PMID- 23129908
TI  - Rheumatic fever pathogenesis: Approach in research needs change.
AB  - Despite identifying that rheumatic fever (RF) is the result of an immunological
      reaction following group-A beta-hemolytic streptococcal infection, the
      pathogenesis remains elusive. RF has been incorrectly designated as causing
      pancarditis, since it does not cause myocarditis. Research directed toward
      myocarditis, targeting myosin to unravel the pathogenesis has not succeeded in
      more than 60 years. RF causes permanent damage to cardiac valves. The mitral
      valve (MV), derived from the wall of the left ventricle, is composed of a central
      core of connective tissue, covered on both sides by endothelium. The left
      ventricle does not have either myocardial or intermyocardial connective tissue
      involvement in RF. By exclusion, therefore, the primary site of RF damage appears
      to be the endothelium. Evaluation of the histopathology and immunopathology
      indicates that RF is a disease of the valvular and vascular endothelium. It is
      not a connective tissue disorder. Research to identify pathogenesis needs to be
      focused toward valvular endothelium.

PMID- 23129909
TI  - The use of Z-scores in paediatric cardiology.
AB  - Z-scores are a means of expressing the deviation of a given measurement from the
      size or age specific population mean. By taking account of growth or age, Z
      scores are an excellent means of charting serial measurements in paediatric
      cardiological practice. They can be applied to echocardiographic measurements,
      blood pressure and patient growth, and thus may assist in clinical decision
      making.

PMID- 23129910
TI  - Unexpected difficulty during transcatheter device closure of atrial septal defect
      associated with right aortic arch.
AB  - Right aortic arch (RAA) associated with isolated atrial septal defect (ASD) is
      very rare. We report successful closure of ASD associated with RAA using a 26-mm
      atrial septal occluder in a 30-year-old male patient. The impingement of right
      descending aorta in RAA caused malposition of the device in the left atrium.
      Deployment of the device through the right upper pulmonary vein successfully
      closed the defect. Follow-up evaluation by computerized tomography scan and
      echocardiogram showed no pulmonary venous obstruction.

PMID- 23129911
TI  - Total anomalous pulmonary venous connection with descending vertical vein:
      Unusual drainage to azygos vein.
AB  - Most patients with total anomalous pulmonary venous connection have a set pattern
      of pulmonary venous drainage and predictable sites of obstruction. However,
      uncommon variations do exist and delineating the entire course is more important
      than just knowing the site of drainage. Azygos vein involvement in the circuit is
      nearly always associated with a complicated course, as was seen in our patient.
      This report reviews the drainage patterns when azygos vein forms a part of the
      circuit.

PMID- 23129912
TI  - A rare association with patent ductus arteriosus.
AB  - Persistent fifth aortic arch (PFAA), also known as congenital double-lumen aortic
      arch, is a rare developmental anomaly of the aortic arch. A 5-month-old baby who
      presented with congestive cardiac failure was diagnosed to have a large patent
      ductus arteriosus with PFAA. Although this arch anomaly had no hemodynamic
      relevance in this case, preoperative diagnosis prevented surprises "on table."

PMID- 23129913
TI  - Myocardial ischemia following arterial switch operation: An uncommon etiology.
AB  - Myocardial ischemia following arterial switch operation (ASO) usually occurs due
      to coronary ostial narrowing that might result from technical failure in
      translocation of the coronary arteries to the neoaorta. We present an unusual
      case report of neonatal myocardial ischemia caused by coronary steal secondary to
      aortopulmonary collaterals, following ASO in transposition of great arteries.

PMID- 23129914
TI  - Infective endarteritis and false mycotic aneurysm complicating aortic
      coarctation.
AB  - A 12-year-old boy with coarctation of aorta developed infective endarteritis and
      mycotic aneurysm at the site distal to coarctation. The computed tomography
      angiogram was very helpful in the diagnosis. Medical management and early
      surgical intervention was curative. Infective endarteritis in coarctation may be
      underdiagnosed.

PMID- 23129915
TI  - Idiopathic isolated annular dilatation causing congenital mitral regurgitation.
AB  - Isolated annular dilatation is an extremely uncommon cause of congenital mitral
      regurgitation. We report a case of a 5-year-old child with idiopathic isolated
      annular dilatation causing severe congenital mitral regurgitation.

PMID- 23129916
TI  - Use of an active fixation lead and a subpectoral pacemaker pocket may not avoid
      Twiddler's syndrome.
AB  - Manipulation of a pacemaker with consequent malfunction of the device has been
      called Twiddler's syndrome. Use of active-fixation leads and subpectoral
      pacemaker pockets has been considered to help in avoiding this problem. We
      describe a child in whom twiddling was not prevented despite implantation of a
      lumenless atrial lead and insertion of the pacemaker generator in a subpectoral
      pocket.

PMID- 23129917
TI  - Factor V Leiden mutation: An added risk in single ventricle palliation.
AB  - We present the case report of a child with Factor V Leiden mutation who underwent
      Fontan procedure. Thromboembolism is a widely recognized complication of the
      Fontan procedure and its modifications. Factor V Leiden mutation, being a
      hypercoagulable state, posed a higher risk for thromboembolism in this child.
      Appropriate measures taken before and after surgery prevented postoperative
      coagulopathy.

PMID- 23129918
TI  - Carotid-subclavian bypass for subclavian steal syndrome following coarctation
      repair in infancy.
AB  - A 19 year old man presented with dizziness that was exacerbated while using left
      arm. On investigation, subclavian steal syndrome (SSS) was diagnosed. He
      underwent left carotid to subclavian bypass with relief of symptoms. Subclavian
      steal syndrome, although rare, should be considered in the differential diagnosis
      in patients with the history of subclavian artery manipulation in the past in
      proper settings.

PMID- 23129919
TI  - Transcatheter interruption of large residual flow after device closure of "Type
      A" patent ductus arteriosus.
AB  - We report a case of 3-year-old girl who had persistence of large residual flow
      following transcatheter closure of a 6 mm 'Type A' patent ductus arteriosus using
      a 12 * 10 mm duct occluder. Angiography revealed a large left-to-right shunt
      coursing through and exiting around the implanted device. Near total abolition of
      the residual shunt was achieved by initial implantation of an embolization coil
      within the duct occluder and subsequently an Amplatzer duct occluder (ADO II)
      adjacent to the duct occluder. This challenging case describes an additional
      technique of abolishing a large residual flow in and around a Nitinol duct
      occluder device.

PMID- 23129920
TI  - Lung herniation into pericardial cavity: A case of partial congenital absence of
      right pericardium.
AB  - Congenital absence of pericardium is rarely seen, often diagnosed
      intraoperatively during cardiac and thoracic surgeries. Left-sided pericardial
      defects are more common than right-sided ones. We present a case of an
      incidentally detected congenital absence of right pericardium with herniation of
      part of the right lung during ventricular septal defect closure surgery in a male
      child aged 4 years.

PMID- 23129921
TI  - A giant left atrial appendage aneurysm with a large pinball-like thrombus in a 2
      year old.
AB  - Congenital left atrial appendage aneurysm is very rare. We describe a giant left
      atrial appendage aneurysm with a pinball-like mobile thrombus in a 2-year-old
      child with cardioembolic stroke. Patient underwent successful surgical resection
      of the aneurysm.

PMID- 23129922
TI  - Selected summaries.

PMID- 23129923
TI  - Society of the Hand and Microsurgeons of India (SOHMI) launches the Journal of
      Hand and Microsurgery.

PMID- 23129924
TI  - Use of a microvascular coupler for repair of major distal upper extremity artery
      injuries.
AB  - BACKGROUND: Non-suturing alternatives to expedite a microanastomoses while still
      insuring maximum patency rates to date have best been achieved using everting
      ring-pin devices. Although these so-called couplers have heretofore primarily
      been used for the venous microanastomosis during free flap transfers, they have
      also had limited value for their arterial counterpart. METHODS: Applications for
      use of the microanastomotic coupler has been extended to repair solitary arterial
      injuries in the distal upper extremity. Over the past year, 4 patients
      specifically with hand or forearm arterial injuries alone, had rapid coupling of
      the injured vessels. RESULTS: Direct end-to-end repair of all hand or forearm
      arterial injuries using a microanastomotic coupler was possible in 3 of four
      cases. Because of the greater extent of injury, the exception required an
      interposition vein graft; but that too was coupled to each end of the divided
      artery in end-to-end fashion. In no case was there any compromise of vascular
      patency. CONCLUSION: Although hand perfusion in no individual in this series was
      ever at jeopardy because of persistent collaterals, this demonstration of the
      efficiency and efficacy of this device may justify future use for critical limb
      revascularisation.

PMID- 23129925
TI  - Comparative study between trapezium resection and tendon interposition with and
      without ligamentplasty in the management of carpometacarpal arthrosis of the
      thumb.
AB  - PURPOSE: Treating arthrosis in the base of the thumb has been a highly
      controverted subject. Many surgeries have been described, such as the isolated
      trapezium resection; resection with interposition with and without ligament
      plasty; arthrodesis, and arthroplasties. The purpose of this paper is to compare
      the two techniques which are currently the most used in this treatment. METHODS:
      A prospective study has been made to compare the surgical results between the
      trapezium resection with tendon interposition (tenoarthroplasty) - 22 cases - and
      tenoarthroplasty associated to ligament plasty-24 cases. Objective evaluation was
      done by measuring opponence, movements of the metacarpophalangeal joint, pinch
      and grasp strength, radiographic measurement of the distance between the base of
      first metacarpal and the scaphoid, and measurement of the angle between the first
      and the second metacarpals. Subjective evaluation was done with a DASH
      questionnaire, visual analog scale to evaluate pain and patient satisfaction.
      RESULTS AND CONCLUSION: After application of the criteria described and using
      Student 't' tests for statistical analysis, the authors concluded that the
      ligament reconstruction has no advantage over the simple resection and tendon
      interposition in carpometacarpal arthrosis of the thumb.

PMID- 23129926
TI  - Preoperative ultrasound in de Quervain's disease: an investigation worth doing.
AB  - BACKGROUND: The diagnosis of de Quervain's disease is traditionally clinical.
      There are no defined objective criteria to select a mode of treatment
      (conservative or surgical). Usually, all cases are initially treated
      conservatively and are offered surgery if it fails. Persistent symptoms after
      surgery, a nightmare for treating surgeon, are attributed to improper diagnosis
      or inadequate release of the compartment. METHODS: A total of 45 symptomatic
      wrists in 42 patients were analyzed. All patients underwent ultrasound
      examination using a 12 MHz linear array transducer by the same radiologist in
      both the affected and unaffected wrists. RESULTS: The highest incidence was seen
      in housewives involved in domestic work. CONCLUSION: Ultrasound is a worthwhile
      preoperative investigation in case of de Quervain's disease.

PMID- 23129927
TI  - Pollicization of the index finger in hypoplasia of the thumb. Experience with the
      method of Buck-Gramcko and retrospective analysis of the clinical outcome in a
      series of 19 pollicizations.
AB  - BACKGROUND: In congenital malformation of the thumb index finger pollicization is
      a proven method for constructing a new thumb all over the world. METHODS: A
      series of 19 pollicizations in 15 patients is presented. In all cases of index
      finger pollicization the method of Buck-Gramcko is used and the functional
      outcome is evaluated after Percival's method. Three special cases are described
      in detail and the preoperative evaluation with a CT-angiography in cases of
      complex malformations (case 3) for better planning of the surgical steps is
      recommended. The importance of parent's information soon after giving birth to a
      child with thumb hypoplasia is described in detail as the postoperative
      management. RESULTS: In children with bilateral deformities of the hand the
      surgery can be performed in one session, in only 2 cases a second operation was
      necessary. The postoperative results were excellent and good (Percival's
      measurement) and the children are now able to perfectly use their affected hand
      in their day-to-day activities. CONCLUSION: Buck-Gramcko's method of
      pollicization in congenital thumb malformation gives excellent results. The
      preoperative planning and exactly following the four key steps is as important as
      the postoperative management.

PMID- 23129928
TI  - The place of local/regional perforator flaps in complex traumas of the forearm.
AB  - BACKGROUND: Our aim was to conduct a retrospective study regarding the advantages
      of doing the all-in-one reconstruction in the same step with the debridement, and
      the possibility of using the local/regional perforator flaps to cover the tissue
      defects. METHODS: We reviewed a series of 137 cases from 1999 until now, for
      acute traumas with tissue defects of the forearm. We performed a regional
      perforator flap in 16 cases, and a local perforator flap in 121 cases. These
      flaps were used for both simple and complex defects coverage, including 26 cases
      with fractures and devascularization. RESULTS: The follow-up was between 2 months
      and 2 years. In all the cases the extremity was salvaged and an useful functional
      recovery was obtained. A very good evolution, with complete survival of the flap
      was recorded in 133 cases. We completely lost only one flap, and registered minor
      complications in three cases. CONCLUSION: The local perforator flaps represent a
      good and safe indication for small and medium defects in the forearm.

PMID- 23129929
TI  - An obstetric brachial plexus data sheet.
AB  - BACKGROUND: Several reputed obstetric brachial plexus clinics use their own
      protocols and indications for surgery. This study is to present and explain the
      obstetric brachial plexus data sheet used at our institution. METHODS: The data
      sheet is composed of 5 main parts: (1) the basic database which includes the
      name, age, type and side of palsy, maternal history, birth history and other
      complications of the traumatic delivery; (2) motor assessment of the limb; (3)
      preoperative investigations; (4) description of intraoperative brachial plexus
      findings and type of nerve procedure performed; and (5) secondary surgery to the
      shoulder, elbow, forearm, wrist and hand. RESULTS: The data sheet was found
      useful in documenting the assessment and events in infants and older children.
      CONCLUSION: An obstetric brachial plexus data sheet is presented and it may be
      modified and used by other centers.

PMID- 23129930
TI  - Directional Doppler and angiography in the assessment of the postoperative
      function of the microvascular anastomoses: a comparative study.
AB  - PURPOSE: The aim was to evaluate the achieved patency rates and to compare
      directional Doppler with angiography in the assessment of the vascular patency.
      METHODS: Two different methods were used in evaluation of the vascular function
      of reconstructed fingers and hands. Directional Doppler mapping of anastomosed
      arteries was compared with conventional angiographical study in the same
      individuals in the examination of 110 arteries. RESULTS: The results showed equal
      findings in majority of examined vessels (93%) using both methods. There was
      erroneous interpretation in Doppler study of 4 arteries and in 3 angiographies
      the interpretation differed from Doppler study mainly due to projection
      difficulty. There were also 4 digital arteries which were considered open in
      Doppler study but angiography showed arterial recanalization or
      neovascularization phenomenon. CONCLUSION: The patency rates at digital artery
      level (70%) were lower than at metacarpal and forearm level (81%) The results
      were in concordance with previous studies.

PMID- 23129931
TI  - Internal headless compression screw method for 4-corner fusion.
AB  - Midcarpal fusion and scaphoidectomy, also referred to as 4 corner fusion, is a
      common treatment for post-traumatic wrist arthritis, either scapholunate advanced
      collapse or scaphoid nonunion advanced collapse. Historically fixation for the
      fusion mass was performed with Kirschner wires. Bone graft was sometimes taken
      from the discarded scaphoid. More recently, articles have focused on the method
      of fixation and its potential role in causing high nonunion rates or specific
      complications. This article offers readers a reliable technique for midcarpal
      fusion designed to minimize both nonunion and hardware related complications.

PMID- 23129933
TI  - Treatment of a symptomatic forearm muscle herniation with a wrap-around fascia
      lata graft.
AB  - Muscle herniation in the extremity is a well-recognized cause of symptomatic pain
      on exertion. Only 17 cases involving the upper limb has been previously
      described, 11 of them involving the anterior compartment of the forearm and only
      2 were caused by strenuous exertion. Treatment for this condition ranged from
      nonsurgical, primary closure with palmaris longus interweave, formal fasciotomy,
      to closure with a tensor fascia lata graft.This is a study of a 28-year-old man
      who had a symptomatic swelling on the volar aspect of his left forearm while
      working on a car-door assembly line that resulted in a significant decreased of
      his grip strength, work capacity and median nerve symptoms. It did not improve
      after 6 months of conservative management including hand therapy and splintage.
      The patient subsequently underwent a tensor fascia lata graft wrap-around.
      Postoperatively his symptoms resolved with improvement in his grip strength and
      hand function. The rationale for the treatment option chosen is discussed.

PMID- 23129932
TI  - Scaphoid reconstruction with vascularized bone grafts from the distal radius.
AB  - The aim of the present technical report is to describe the alternative solutions
      for the reconstruction of scaphoid nonunions with pedicled vascularized bone
      grafts from the distal radius. The surgical technique for the reconstruction A.
      of proximal scaphoid nonunions with pedicled bone grafts (based on the 1,2 or on
      the 2,3 intercomparmtental arteries) or with capsular bone grafts from the dorsal
      distal radius and B. of waist nonunions of the scaphoid with grafts from the
      palmar distal radius, pedicled on the palmar carpal arch, is presented.
      Vascularized bone grafts from the adjacent radius are used for the treatment of
      scaphoid nonunions to enhance union and to revascularize a nonviable proximal
      pole. The most suitable graft is selected according to the location of the
      nonunion (at the waist or the proximal pole of the scaphoid) and to the previous
      procedures/scars at the wrist level.

PMID- 23129934
TI  - Recent advances in wrist trauma.

PMID- 23129935
TI  - Major upper extremity replantations.
AB  - The usual mechanism of a major amputation creates a mutilating injury. Although
      survival rate is high, the functional results are guarded [1, 2]. The aim of this
      study is to review our experience with major upper extremity replantations
      performed between the years 1987-2007 with respect to the type of amputation as
      proposed by Chuang et al. [3]. 23 upper extremities were replanted in 22 patients
      (7 arms and 16 proximal forearms and elbows). All but one replanted parts
      survived. Out of 6 patients with arm replants 4 gained useful extremities and two
      had poor result after more than 2 years of rehabilitation and 17 additional
      surgical procedures. Out of 16 replanted forearms, after more than 2 years of
      rehabilitation period and 50 operations, useful extremity was achieved in 11 and
      poor result in 5. The main factor influencing functional result was the type of
      amputation according to Chuang et al. [3].

PMID- 23129936
TI  - Patient-centered care of de Quervain's disease.
AB  - PURPOSE: To test the hypothesis that most patients that elect symptomatic
      treatment of de Quervain's disease experience symptom resolution. MATERIALS AND
      METHODS: Eighty-three of 314 (26%) patients that elected initial symptomatic
      treatment of de Quervain's disease responded to a mail survey inquiring about
      symptom resolution, symptom duration, subsequent opinions and treatments, final
      impressions and comments. RESULTS: Seventy-five respondents (90.4%) reported
      resolution of the pain, including 58 of the 61 (95%) respondents that elected
      neither corticosteroid injection nor surgery. Among patients with symptom
      resolution without injection or surgery 48 of 58 (83%) recalled symptoms for
      fewer than 12 months. The differences in reported average time to symptom
      resolution were not statistically significant between patients that elected or
      did not elect a corticosteroid injection. CONCLUSIONS: Considered in the light of
      important limitations of this data including the reliance on patient recall and
      the limited response rate to the survey, the data are still intriguing. At least
      in one surgeon's practice, most informed patients initially elect symptomatic
      treatment, and most experience symptom resolution within one year.

PMID- 23129937
TI  - Total wrist arthroplasty: A review.
AB  - Total wrist arthroplasty was first performed over a hundred years ago. However,
      it did not prove a viable option until the late 1960s with the advent of the
      Swanson implant. Since then there have been many advances. The changes in design,
      and their rationale, are discussed in this article. The latest implants, the
      advances made and the indications for surgery are addressed.

PMID- 23129938
TI  - Cubital tunnel syndrome - Review of current literature on causes, diagnosis and
      treatment.
AB  - Cubital tunnel syndrome is common, but not fully understood. Fortunately, most
      cases of ulnar nerve compression improve with nonsurgical treatment and large
      majority get better with surgical decompression. The fact that most people get
      better with and without surgical treatment is likely the reason that multiple
      studies have failed to show improved results with different types of
      decompressions for mild cubital tunnel syndrome. Transposition surgeries have
      been shown to yield better results with more severe cases and patients who failed
      previous simple releases, likely secondary to release of other compression sites
      that were missed by the initial surgery. Knowing more about pathology of the
      cutbital tunnel syndrome such as compression versus traction injury and having
      better modalities for evaluation of the nerve should help us to better tailor
      treatment for the patients in the future.

PMID- 23129940
TI  - The functional anatomy of forearm rotation.
AB  - The elbow, forearm and wrist act as a unified structure to provide a stable,
      strong and highly mobile strut for positioning the hand in space and for
      conducting load-bearing tasks. An understanding of the relevant anatomy and
      biomechanics is important for the surgeon assessing and treating disorders of
      forearm function. This paper is concerned with illuminating the principles and
      concepts governing forearm rotation and load-bearing functions.

PMID- 23129941
TI  - Universal 2 total wrist arthroplasty.
AB  - The Universal 2 wrist replacement is considered my many to be the implant of
      choice in patients with inflammatory arthropathy requiring joint replacement. The
      procedure is discussed in this article and technical aspects considered.

PMID- 23129939
TI  - The role of locking technology in the upper extremity.
AB  - The technique of locked plating has been a major advance in Orthopaedic fracture
      surgery and has had an equal impact on the management of upper extremity
      fractures. The recognition of the role of vascularity and soft tissues in
      fracture healing was central to the research and development of newer plate
      designs that left minimal footprints on the surface of the bone. Subsequently,
      innovative locking technology has improved our ability to manage cases with
      extensive communition, inadequate bone stock, and peri-articular fractures. This
      paper will review the role of locking technology in the management of fractures
      of the upper extremity.

PMID- 23129942
TI  - Subcapital ulnar shortening osteotomy.
AB  - Ulnar shortening osteotomy is the standard treatment for the condition of
      ulnocarpal impaction. Traditionally ulnar shortening osteotomy has been performed
      in the diaphysis and secured with a 3.5 mm plate. Delayed union, nonunion, and
      symptomatic hardware have been cited as detractors of this technique. A number of
      alternatives have consequently been proposed that range from different hardware
      to different patterns of osteotomy to resection of the distal portion of the
      ulnar head. This article describes one method for ulnar shortening osteotomy that
      seeks to draw upon the advantages of several of these variations in order to
      minimize complications.

PMID- 23129943
TI  - Isolated posttraumatic ulnar translocation of the radiocarpal joint.
AB  - An isolated posttraumatic ulnar translocation of the carpus is unusual. In cases
      in which the translocation occurs without accompanying injury to distal radius,
      ulna, or carpal bones, the diagnosis is often delayed due to the unfamiliarity of
      the treating physician with this rare radiographical finding. By presenting two
      patients with such an injury, we hope to increase awareness of this injury.

PMID- 23129945
TI  - Hand transplantation in India - not miles ahead.

PMID- 23129944
TI  - Guyon's canal syndrome: a rare case of venous malformation.
AB  - This paper describes an unusual case of parasthesia in the medial two fingers of
      the hand in a 56-yearold lady. MRI suggested a space occupying lesion and on
      exploration this proved to be a venous malformation causing a pressure neuropathy
      of the ulnar nerve.

PMID- 23129946
TI  - Complications of extensor tendon repairs at the extensor retinaculum.
AB  - Literature describing surgical, post-operative management and outcomes following
      EDC repairs in close proximity to or within the extensor retinaculum is limited.
      This complex injury can result in decreased wrist and digital motion as well as
      loss of independent motion of the digits. This paper reviews complications
      following such injuries observed clinically as well as experimental simulation
      performed on cadaveric specimens. Our observations have direct implications to
      hand therapy practice and outcomes used following such injuries.

PMID- 23129948
TI  - Association between psychosocial factors and pain in patients with trigger
      finger.
AB  - PURPOSE: To test the hypothesis that psychological factors correlate with pain
      intensity in trigger finger (TF). METHODS: Patients with TF were selected from
      two previous cohort studies measuring pain intensity and psychological
      parameters, 82 from one study and 72 from another. Correlation testing and
      multiple linear regression was performed. Measures included the pain
      catastrophizing scale (PCS), pain self-efficacy questionnaire (PSEQ), patient
      health questionnaire depression (PHQ-D) scale, center for epidemiologic studies
      depression (CES-D) scale, pain anxiety symptoms score (PASS), and the eysenck
      personality questionnaire (EPQ-R) scales. RESULTS: There was moderate correlation
      between pain intensity and PCS (rho = 0.52; P < 0.001) and PSEQ (rho = - 0.36; P
      < 0.001). There was weak correlation between pain and PHQ-D (rho = 0.23; P =
      0.019). No significant correlation existed with CES-D or EPQ-R. PCS accounted for
      26% of the variance in pain for patients awaiting surgery (P < 0.001).
      CONCLUSION: Self-reported pain in TF has moderate correlation with psychological
      factors, most predominantly pain catastrophizing.

PMID- 23129947
TI  - Outcome of index finger pollicisation.
AB  - BACKGROUND: Pollicisation of the index finger for absence or severe hypoplasia of
      the thumb has been reported as a good procedure to recreate a new 'thumb' with
      good cosmesis and acceptable function. The purpose of this study is to evaluate
      the outcome of our series from different viewpoints. METHODS: Seventeen patients
      with 24 involved hands were willing to come back for evaluation. The mean age at
      operation was 12 months. In 8 hands there was also a radial club hand. Buck
      Gramcko's technique was used with slight modifications. The mean follow-up time
      was 53 months (ranging from 6 to 142). The outcome was determined in a variety of
      ways: the functional assessment, cosmesis (objectivated with measurement of thumb
      length, girth and nail size) and a subjective evaluation of function and aspect
      done with a patient/parent questionnaire and a visual analogue score. RESULTS:
      The mean functional score was: one excellent, eleven good, five fair and five
      poor results. The mean length was 96% the width was 93%, the nail width was 85%.
      There was no significant different outcome in the syndrome related thumbs versus
      the isolated cases, unilateral versus bilateral cases. A significant worse
      outcome was seen for function and subjective evaluation in the radial club hand
      associated thumbs and for the functional score for the more severe Blauth group.
      CONCLUSION: The general outcome for non radial club hand associated thumb
      reconstructions was satisfying. There was good correlation between the different
      scoring systems.

PMID- 23129949
TI  - Digital intraosseous epidermoid inclusion cyst of the distal phalanx.
AB  - Epidermoid inclusion cysts (EIC) of the bone are exceedingly rare. We present a
      case of an atypical EIC originating at the base of the distal phalanx of the
      index finger following a remote history of crush injury to the finger. The
      differential diagnosis of expansile, lytic lesions of the phalanges remains
      broad, and definitive diagnosis requires tissue histopathological analysis. At
      latest follow-up, the patient was pain-free and obtained an excellent clinical
      and radiographic outcome following intra-lesional curettage and bone grafting.
      Differentiation of EIC from other radiolucent digital lesions remains
      challenging, especially when classic radiographic findings are not seen. We
      review the clinical, radiographic, and pathologic diagnostic features of this
      lesion, as well as our current treatment algorithm.

PMID- 23129950
TI  - The use of Teno Fix tendon repair device in a patient with multiple flexor tendon
      ruptures.
AB  - Flexor tendon laceration repairs remain challenging despite numerous advances in
      hand surgery. Although progress on this vital subject matter has been achieved,
      there continues to be discussion over which surgical technique produces the
      optimal result. Currently there are several recommended surgical repair options
      for the lacerated flexor tendon. However, these repairs continue to have possible
      significant complications including adhesions, decreased range of motion,
      gapping, and post operative rupture. Stainless steel suture has long been known
      as an option for flexor tendon repair. Stainless steel suture demonstrates one of
      the highest tensile strength sutures. However until recently, stainless steel
      suture placement for flexor tendon repairs was technically problematic. This case
      study discusses an additional option for repairing lacerated flexor tendons using
      an advanced stainless steel tendon repair system.

PMID- 23129951
TI  - Impingement of a fibroma of the extensor tendon sheath on the extensor
      retinaculum.
AB  - Deep lacerations to the forearm can cause impaired movement of the digits. This
      report describes the presentation and management of a self-harmer who presented
      with loss of motion of her ring finger. Surgical exploration unexpectedly
      demonstrated the cause to be a fibroma of the tendon sheath impinging on the
      extensor retinaculum. Full recovery was demonstrated at sixmonth review following
      removal of the lesion.

PMID- 23129953
TI  - Longitudinal dysplasia with humerus buried within soft tissue of the chest wall.
AB  - We describe a patient presenting with upperextremity longitudinal dysplasia in
      whom the humerus was buried within the tissues of the chest wall. Surgery was
      performed to elevate the left humerus from the upper chest and place it within
      the empty soft tissue envelope, which extended distally from the shoulder. To our
      knowledge, this particular anomaly has not been previously described in the
      literature.

PMID- 23129952
TI  - Strategic two-stage approach to radial club hand.
AB  - In patients with radial club hand (RCH), there is absence of the radius and
      severe hypoplasia of the thumb, so both wrist stabilization and thumb
      reconstruction are essential. When wrist stabilization is performed, recurrence
      of angulation is a problem. When thumb reconstruction is done, preservation of at
      least one major dorsal vein is important to prevent necrosis of the reconstructed
      thumb. We executed a strategic approach to RCH, which aimed to prevent both
      recurrence of angulation and necrosis of the reconstructed thumb.

PMID- 23129954
TI  - Extensor pollicis longus dysfunction associated with non-united fracture of the
      trapezium.
AB  - A 26 year old man was referred to us with extensor pollicis longus dysfunction
      (EPL), and investigation revealed a fracture of the trapezium (left) and carpo
      metacarpal joint dislocation of the thumb. Operative exploration revealed
      mechanical displacement of the tendon secondary to fracture dislocation of the
      trapezium as the cause for EPL dysfunction. The lesion was managed with an open
      reduction and screw fixation resulting in good functional outcome.

PMID- 23129955
TI  - Are we going to allow the last nail on the coffin of animal experimentation to be
      nailed?

PMID- 23129957
TI  - Comparative evaluation of adverse drug reaction reporting forms for introduction
      of a spontaneous generic ADR form.
AB  - Despite comprehensive and stringent phases of clinical trials and surveillance
      efforts, unexpected and serious adverse drug reactions (ADRs) repeatedly occur
      after the drug is marketed. ADR reporting is an important aspect of an efficient
      and effective pharmacovigilance program. Although Medwatch, Yellow Card, CDSCO
      form, etc. are the protocol forms of ADR collection and reports, a number of
      countries design and use their respective ADR forms. This review compares
      similarities and dissimilarities of 13 ADR forms of countries representing their
      geographical location. This study extracted 73 data elements mentioned in 13
      different ADR forms. Only 13 elements were common. An ADR form of Malaysia and
      Canada covers the highest number of data 43, while Brazil falls to the opposite
      end with a number of 17 data elements in lieu with the Generic ADR Form. The
      result of this review highlights 58 data elements of the proposed generic ADR
      form which ensures that requisite reporting information essential for correct
      causality assessment of ADRs are included. The proposed "Generic ADR form" could
      be adopted worldwide mandatorily for reporting any/all ADRs associated with
      marketed drugs.

PMID- 23129956
TI  - MicroRNAs as newer therapeutic targets: A big hope from a tiny player.
AB  - MicroRNAs (miRNAs) are a novel group of universally present small noncoding
      endogenous RNAs that regulate gene expression and protein coding by base pairing
      with the 3' untranslated region (UTR) of target mRNAs. So they have been
      associated with several physiological processes and play an important role in the
      manifestation of diverse diseases. miRNAs expression is associated with the
      normal and diverse pathophysiological state including cardiac hypertrophy,
      neurodegenerative diseases, diabetes and its complication, and cancer because
      individual miRNAs are associated with the regulation of the expression of
      multiple target genes. Modulating the expression of a single miRNA can influence
      an entire gene network and thereby modify complex disease phenotypes. From recent
      studies, it has been confirmed that miRNA has a potential physiological role in
      various body systems. But in some specialized condition over expression of miRNA
      within the cytoplasm also leads to some pathological condition in the body. Here,
      we summarize the roles of miRNAs in various pathological conditions and consider
      the advantages and potential challenges of miRNA-based therapeutic approaches
      compared to conventional drug-based therapies.

PMID- 23129958
TI  - Induction of cell-specific apoptosis and protection of mice from cancer challenge
      by a steroid positive compound from Zornia diphylla (L.) Pers.
AB  - OBJECTIVES: Zornia diphylla (L.) Pers is an ethnomedical herb. The aim of the
      study is to scientifically verify the traditional use of Z. diphylla as an
      anticancer medicine. MATERIALS AND METHODS: Different extracts, fractions, and
      chemical isolates of the whole plant were screened for cytotoxicity to Dalton's
      lymphoma ascites (DLA) cells by the Trypan blue exclusion method and MTT assay.
      Column chromatographic and preparative TLC techniques were used for the isolation
      of active fraction (AF) and active principle. Cytotoxicity of AF to different
      cell types was tested. The apoptotic activity of AF was evaluated by
      morphological observations, nuclear condensation, and comet assay. In vivo
      antitumor activity of AF was determined in DLA-challenged mice. Short-term (29
      days) preliminary toxicity evaluation of AF was done in mice. RESULTS: n-Hexane
      extract (but not water and ethanol extracts) showed significant cytotoxicity. AF,
      isolated from n-hexane extract, induced apoptotic cell death (in vitro) to DLA
      cells, but not to normal thymocytes and macrophages. A steroid positive active
      principle was isolated which showed 100% cytotoxicity at 5 MUg/mL level.
      Interestingly, AF (50 mg/kg) protected all the mice challenged with one million
      DLA cells/mouse. AF (up to 10 times higher than the therapeutic dose) did not
      exhibit any conspicuous adverse toxic symptoms in the toxicity evaluation.
      CONCLUSION: Z. diphylla (AF) showed promising in vitro and in vivo anticancer
      activity against DLA cells, and it was devoid of any toxicity to mice in short
      term toxicity evaluation. The herb is promising for the development of a valuable
      anticancer medicine.

PMID- 23129959
TI  - Impact of clinical pharmacist interventions on the cost of drug therapy in
      intensive care units of a tertiary care teaching hospital.
AB  - OBJECTIVE: To analyze clinical pharmacist interventions in the intensive care
      units (ICUs) setting of a tertiary care Indian hospital and to assess the
      pharmacoeconomic impact on drug-related problems (DRPs). MATERIALS AND METHODS: A
      postgraduate clinical pharmacist reviewed drug prescriptions over a period of 7
      months. Whenever a DRP is identified, it was discussed with a physician and
      appropriate suggestions were provided, later it was documented on a preprepared
      form. Clinical significance of each intervention was graded based on the
      predicted clinical outcome. Acceptance of the interventions is entirely at the
      discretion of the medical staff. Each intervention was analyzed with respect to
      potential cost saving and/or additional cost incurred to existing drug therapy.
      An independent clinical panel was convened, and all the interventions made by the
      intervening pharmacist were critically reviewed for potential cost savings.
      RESULTS: The intervening pharmacist made 117 recommendations, of which 94% was
      accepted by the medical professionals. The most frequent DRP identified was
      overdose (24%). The total net cost savings made was Rs. 77260.13 (USD 1796.73).
      This corresponds with Rs. 965.75 per patient and an annualized savings of Rs.
      135205.22. CONCLUSION: Clinical pharmacist interventions had a significant impact
      on the cost of drug therapy and the patient outcome in intensive care settings of
      our hospital.

PMID- 23129960
TI  - Metformin ameliorates methotrexate-induced hepatotoxicity.
AB  - OBJECTIVE: To study the effect of metformin on amelioration of hepatotoxicity
      induced by methotrexate. MATERIALS AND METHODS: After a 2-weeks of
      acclimatization period, the animals were randomly separated into three groups
      (seven rabbits each), all groups were maintained on standard chow diet throughout
      the experiment (8 weeks). Group 1 was treated with normal saline water (control),
      Group 2 with methotrexate (MTX, hepatotoxic), and Group 3 with MTX plus
      metformin. Induction of hepatotoxicity was carried out by administration of MTX
      to the rabbit in a dose of 0.25 mg/kg /day i.m. for 8 weeks. RESULTS: The
      treatment with MTX to rabbits for 8 weeks resulted in significant changes in
      serum liver enzymes, as compared to the baseline group. SGOT, SGPT, ALP, and
      bilirubin were significantly increased (P < 0.001), while total serum protein was
      significantly decreased. Similarly, 8 weeks of MTX treatment produced significant
      (P < 0.001) prolongation in PT. PTT was not significantly changed. It was found
      that serum MDA levels and SOD activity were significantly increased (P < 0.001),
      while serum GSH levels were significantly decreased (P < 0.001). Adding metformin
      to MTX is found to be significantly (P < 0.001) reduced the liver function test
      and shortening of PT and a significant increase in TSP (P < 0.001). CONCLUSION:
      It can be concluded that administration of metformin restored the altered liver
      function parameters and produced significant improvement in liver
      histopathological findings. Therefore, this additive drug possesses
      hepatoprotection against MTX-induced hepatotoxicity.

PMID- 23129961
TI  - A prospective study to compare the effects of pre, intra and post operative
      steroid (dexamethasone sodium phosphate) on post tonsillectomy morbidity.
AB  - OBJECTIVE: To determine the effectiveness of dexamethasone on post tonsillectomy
      morbidities in patients with chronic tonsillitis. MATERIALS AND METHODS: In this
      randomized double-blind study, 100 patients who underwent tonsillectomy were
      enrolled and were randomly allocated into control or dexamethasone group (pre
      operative, intra operative and post operative groups). Patients were assessed for
      pain nausea, vomiting and oral intake in the post operative period at 24 h.
      RESULTS: Patients treated with dexamethasone particularly in the pre and intra
      operative groups (Group B, Group C) showed a general trend towards lower pain
      score than post operative group (Group D). The scores were about 1.72+/-0.84 and
      2.20+/-1.19 in Groups B and C respectively, and 2.64+/-0.99 in Group D. Overall
      pain score was found to be more in the control Group A about 4.84+/-1.21 at 6 h
      post operatively and showed similar trend for next 24 h. Total number of patients
      with nausea was significantly high about 84% in control group compared to
      dexamethasone groups (Group B, C and D) about 20%, 8% and 24% respectively and
      also incidence of vomiting episodes showed a similar trend. Oral intake was
      significantly delayed in control group (6.16 +/-1.52), P < 0.001 than
      dexamethasone group. Pre operative and intra operative groups showed early intake
      (3.68+/-0.68) and (3.60+/-1.12) respectively than the postoperative group (5.08+/
      0.95). CONCLUSIONS: A single intravenous dose of dexamethasone, given following
      induction of anaesthesia and at the time of surgery, provided prolonged
      analgesia, reduced nausea and vomiting and resulted in earlier oral intake.

PMID- 23129962
TI  - Prevalence and pattern of sexual dysfunction in married females receiving
      antidepressants: An exploratory study.
AB  - OBJECTIVE: To study the prevalence and patterns of sexual dysfunctions in female
      patients receiving antidepressants. MATERIALS AND METHODS: Eighty married female
      patients with a diagnosis of depressive disorder, currently in remission, and
      receiving a single antidepressant at least for 3 months, were assessed for sexual
      dysfunction on female sexual function index (FSFI) scale. RESULTS: Thirty four
      patients (42.5%) receiving antidepressants had FSFI score less than 26.55 and
      were considered to have sexual dysfunction. When only the domain cutoff scores
      were used for the whole study sample (n=80), it was found that 95% had decreased
      desire, 60% had decreased arousal, 37.5% had decreased lubrication, 63.8 had
      decreased orgasm, 55% had decreased satisfaction and 25% had pain during sexual
      activity. CONCLUSIONS: To conclude, our study suggests that sexual dysfunction is
      quite prevalent in married female patients receiving antidepressants and all the
      domains of sexual functioning are impaired by antidepressants.

PMID- 23129963
TI  - A retrospective study of extrapyramidal syndromes with second generation
      antipsychotics in the psychiatric unit of a tertiary care teaching hospital.

PMID- 23129964
TI  - Physicians' and patients' opinions on the use of generic drugs.

PMID- 23129965
TI  - Determinants of success of loading dose diazepam for alcohol withdrawal: A chart
      review.

PMID- 23129966
TI  - Effect of Abrus precatorius and Amaranthus spinosus combination treatment on
      fertility in male rats.

PMID- 23129967
TI  - A prescription survey in diabetes assessing metformin use in a tertiary care
      hospital in Eastern India.

PMID- 23129968
TI  - Toxic epidermal necrolysis caused by fluconazole in a patient with human
      immunodeficiency virus infection.
AB  - Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN) are rare but
      serious dermatologic disorders. These grave conditions present as medical
      emergency, requiring prompt diagnosis and management. These are often drug
      induced and various groups of drugs, such as sulfa drugs, NSAIDS, etc., have been
      implicated as to cause TEN. Fluconazole is a commonly used drug with mild side
      effects. TEN caused by fluconazole is rare, and till now only few cases have been
      reported in the literature. We present a case of TEN in a human immunodeficiency
      virus infected man following fluconazole therapy in view of its rare occurrence.

PMID- 23129969
TI  - Aripiprazole-induced oculogyric crisis (acute dystonia).
AB  - Aripiprazole is the third generation atypical antipsychotic and a dopamine
      serotonin system stabilizer (DSS) effective against positive and negative
      symptoms of schizophrenia. It has a low propensity for extrapyramidal side
      effects, causes minimal weight gain or sedation, produces no elevation in serum
      prolactin levels, and does not cause prolongation of QTc interval. This case
      report is of a patient suffering from schizophrenia (paranoid). The patient
      developed oculogyric crisis (acute dystonia) with aripiprazole dose uptitration.
      Dystonic reaction resolved with promethazine administration. Naranjo's causality
      assessment reveals probable association of aripiprazole with oculogyric crisis. A
      thorough workup and vigilance is required prior to initiation of aripiprazole in
      the case of schizophrenia.

PMID- 23129970
TI  - Acute myocardial involvement after heroin inhalation.
AB  - Amongst the illicit drugs cocaine, amphetamines and cannabis have been studied
      and documented well to cause myocardial infarction by different mechanisms but
      there is very sparse data available on myocardial involvement after heroin abuse.
      We report a young man who developed acute myocardial injury after heroin
      inhalation and alcohol binge drinking. Heroin induced cardio toxic effect and
      vasospasm compounded by alcohol were suspected to be the cause of this.

PMID- 23129971
TI  - L-Asparaginase induced thrombosis in acute lymphoblastic leukemia.

PMID- 23129972
TI  - Author's reply.

PMID- 23129973
TI  - Guide to pharmacology.

PMID- 23129974
TI  - Fospropofol.

PMID- 23129975
TI  - Socioeconomic Context and Emotional-Behavioral Achievement Links: Concurrent and
      Prospective Associations Among Low- and High-Income Youth.
AB  - Temporal associations in the relationship between emotional-behavioral difficulty
      and academic achievement were explored in 2 samples followed from 6th through 8th
      grade. The first sample comprised 280 students entering an economically
      disadvantaged urban middle school and the second comprised 318 students entering
      an affluent suburban middle school. Among disadvantaged youth, emotional indices
      were concurrently associated with poorer achievement while prospective
      associations between substance use and achievement were evident. For privileged
      adolescents, only a significant concurrent relationship emerged between social
      anxiety and achievement, although nonsignificant trends in the data suggest
      other, albeit weak, associations. The findings are discussed in terms of
      similarities and differences in these temporal associations across 2 samples
      representing extremes of the socioeconomic continuum.

PMID- 23129977
TI  - Effects of Treadmill Exercise on the Recovery of Dopaminergic Neuron Loss and
      Muscle Atrophy in the 6-OHDA Lesioned Parkinson's Disease Rat Model.
AB  - This study was to determine the effect of exercise on the recovery of
      dopaminergic neuron loss and muscle atrophy in 6-OHDA-induced hemi Parkinson's
      disease model. Exercise was loaded twice per day for 30 minutes each time, at 5
      days after 6-OHDA lesioning and continued for 16 days using a treadmill. Exercise
      significantly increased the number of tyrosine hydroxylase positive neuron in the
      lesioned substantia nigra and the expression level of tyrosine hydroxylase in the
      striatum compared with the control group. To examine which signaling pathways may
      be involved in the exercise, the phosphorylation of GSK3beta and ERK were
      observed in the striatum. In the control group, basal level of GSK3beta
      phosphorylation was less than in both striatum, but exercise increased it. ERK
      phosphorylation decreased in the lesioned striatum, but exercise recovered it.
      These findings suggest that exercise inactivates GSK3beta by phosphorylation
      which may be involved in the neuroprotective effect of exercise on the 6-OHDA
      induced cell death. In the exercise group, weight, and Type I and II fiber cross
      sectional area of the contralateral soleus significantly recovered and expression
      of myosin heavy chain and Akt and ERK phosphorylation significantly increased by
      exercise. These results suggest that exercise recovers Parkinson's disease
      induced dopaminergic neuron loss and contralateral soleus muscle atrophy.

PMID- 23129978
TI  - The millipede family Ammodesmidae (Diplopoda, Polydesmida) in western Africa.
AB  - Ammodesmidae are represented in western Africa by two species of a single genus,
      Ammodesmus Cook, 1896 (= Cenchrodesmus Cook, 1896, syn. n.). The type-species
      Ammodesmus granum Cook, 1896 (= Cenchrodesmus volutus Cook, 1896, syn. n.) is
      redescribed, based on neotype selection, as well as on additional samples, often
      containing numerous specimens, from Liberia, Guinea and the Ivory Coast. A new
      species is described from Mount Nimba, Guinea: Ammodesmus nimbasp. n.

PMID- 23129976
TI  - Light-dependent changes in outer retinal water diffusion in rats in vivo.
AB  - PURPOSE: To test the hypothesis that in rats, intraretinal light-dependent
      changes on diffusion-weighted magnetic resonance imaging (MRI) in vivo are
      consistent with known retinal layer-specific physiology. METHODS: In male Sprague
      Dawley rats, retinal morphology (thickness, extent, surface area, volume) and
      intraretinal profiles of the apparent diffusion coefficient (ADC, i.e., water
      mobility) parallel and perpendicular to the optic nerve were measured in vivo
      using quantitative MRI methods during light and dark stimulation. RESULTS: The
      parallel ADC in the posterior half of the avascular, photoreceptor-dominated
      outer retina was significantly higher in light than dark, and this pattern was
      reversed (dark>light) in the anterior outer retina. The perpendicular ADC in the
      posterior outer retina was similar in light and dark, but was significantly
      higher in dark than light in the anterior outer retina. No light-dark changes in
      the inner retina were noted. CONCLUSIONS: We identified light-dependent
      intraretinal diffusion changes that reflected established stimulation-based
      changes in outer retinal hydration. These findings are expected to motivate
      future applications of functional diffusion-based MRI in blinding disorders of
      the outer retina.

PMID- 23129979
TI  - Redescription of arenicolous dipluran Parajapyx pauliani (Diplura, Parajapygidae)
      and DNA barcoding analyses of Parajapyx from China.
AB  - Littoral dipluran Parajapyx pauliani Pages, 1959 was redescribed based on the
      specimens collected in Hainan Island, South China. The littoral habitat was
      confirmed for the species, as the first report of arenicolous dipluran in China.
      DNA barcoding fragment was sequenced for five Parajapyx species (18 individuals)
      from China, and this is the first report on DNA barcodes used for dipluran
      identification. The mean intra- and interspecific divergencesare 1.9% and 19.1%
      respectively. Synonymy of Parajapyx paucidentis and Parajapyx isabellae was
      confirmed.

PMID- 23129980
TI  - A revision of the Megachile subgenus Litomegachile Mitchell with an illustrated
      key and description of a new species (Hymenoptera, Megachilidae, Megachilini).
AB  - The species of Megachile subgenus Litomegachile are revised with a review of the
      species morphology, biology, and plant associations. A new species, Megachile
      pankus, is described and illustrated. Megachile mendica snowi Mitchell is
      elevated to species. Megachile var. nupta Cresson and Megachile texana var.
      cleomis Cockerell are synonymized with Megachile brevis and Megachile texana,
      respectively. An illustrated key for Litomegachile is also provided.

PMID- 23129981
TI  - Two new species of Euglossa from South America, with notes on their taxonomic
      affinities (Hymenoptera, Apidae).
AB  - Two new species of the genus Euglossa Latreille, subgenus Glossurella Dressler
      are here presented. Euglossa (Glossurella) emberasp. n., from the Pacific
      lowlands of Colombia, and Euglossa (Glossurella) adiastolasp. n., from the
      Atlantic Forest of Brazil. Their taxonomic association and distinction are
      discussed, as well as the correct understanding of the subgenus Glossurella.

PMID- 23129982
TI  - Species of Adialytus Forster, 1862 (Hymenoptera, Braconidae, Aphidiinae) in Iran:
      taxonomic notes and tritrophic associations.
AB  - The species of Adialytus Forster in Iran are taxonomically studied and new data
      on distribution and host associations are presented. The existence of a species
      complex, in the case of Adialytus ambiguus (Haliday), and the morphological
      variability in commonly used taxonomic characters has been discussed. In total,
      four valid species belonging to the genus Adialytus including Adialytus ambiguus
      (Haliday), Adialytus salicaphis (Fitch), Adialytus thelaxis (Stary) and Adialytus
      veronicaecola (Stary) have been identified and recorded from Iran. Also, we
      recognized two additional phenotypes: "Adialytus arvicola" (Stary) and "Adialytus
      cf. ambiguus" (Haliday). These phenotypes and Adialytus veronicaecola are newly
      recorded from Iran in association with Sipha and Aphis species, respectively. An
      illustrated key for identification of the species and two variable phenotypes is
      presented.

PMID- 23129983
TI  - A taxonomic contribution to the genus Dolichomitus Smith (Hymenoptera,
      Ichneumonidae, Pimplinae) from Brazil.
AB  - In the present study, two new species of Pimplinae, Dolichomitus jataisp. n. and
      Dolichomitus moacyrisp. n. are described, and the distribution range of
      Dolichomitus annulicornis (Cameron, 1886) is extended. The specimens were
      collected using Malaise traps in areas of Atlantic forest and Brazilian savannah
      (cerrado) in southeastern Brazil and are deposited in a Brazilian collection
      (DCBU).

PMID- 23129984
TI  - Aphaereta ceratitivora sp. n. (Hymenoptera, Braconidae), a new parasitoid of
      Ceratitis capitata (Wiedemann) (Diptera, Tephritidae) from the Azores.
AB  - A new gregarious larval-pupal endoparasitoid of Ceratitis capitata (Wiedemann)
      (Diptera: Tephritidae) is described and illustrated: Aphaereta ceratitivorasp. n.
      (Braconidae: Alysiinae: Alysiini).

PMID- 23129985
TI  - Review of the species level taxonomy of the neotropical butterfly genus Oenomaus
      (Lycaenidae, Theclinae, Eumaeini).
AB  - Seven new species of the Neotropical hairstreak genus Oenomaus are described:
      Oenomaus mancha Busby & Faynel, sp. n. (type locality Ecuador); Oenomaus gwenish
      Robbins & Faynel, sp. n. (type locality Panama); Oenomaus lea Faynel & Robbins,
      sp. n. (type locality Ecuador); Oenomaus myrteana Busby, Robbins & Faynel, sp. n.
      (type locality Ecuador); Oenomaus mentirosa Faynel & Robbins, sp. n. (type
      locality Peru); Oenomaus andi Busby & Faynel, sp. n. (type locality Ecuador) and
      Oenomaus moseri Robbins & Faynel, sp. n. (type locality Brazil, Santa Catarina).
      For each new Oenomaus species, we present diagnostic characters and notes on its
      habitat and biology. We illustrate adults, genitalia, and distribution. New
      distributional and biological data are presented for 21 previously described
      Oenomaus species. Oenomaus melleus guyanensis Faynel, 2008 is treated as a new
      synonym of Oenomaus melleus melleus (Druce, 1907). Females are described and
      associated with males for ten species using a variety of factors, including
      mitochondrial COI DNA "barcode" sequences. We summarize the reasons why the
      number of recognized Oenomaus species has grown in the past decade from one
      species to 28 species. Finally, we overview the habitats that Oenomaus species
      occupy and note that the agricultural pest on Annonaceae, Oenomaus ortygnus, is
      the only Oenomaus species that regularly occurs in greatly disturbed habitats.

PMID- 23129986
TI  - Three new cryptic species of Euglossa from Brazil (Hymenoptera, Apidae).
AB  - Three new species of orchid bees are described and figured from the Amazon and
      Atlantic forests of Brazil. Euglossa clausisp. n., Euglossa moratoisp. n., and
      Euglossa pepeisp. n. are distinguished from their close congeners Euglossa
      crassipunctata Moure, Euglossa parvula Dressler, and Euglossa sapphirina Moure,
      previously placed in the subgenus Euglossa (Glossurella) Dressler, 1982, a
      demonstrably paraphyletic assemblage requiring serious reconsideration. Their
      affinities with related species are discussed and pertinent characters are
      figured.

PMID- 23129987
TI  - On the occurrence of egg masses of the diamond-shaped squid Thysanoteuthis
      rhombus Troschel, 1857 in the subtropical eastern Atlantic (Canary Islands). A
      potential commercial species?
AB  - Data on opportunistic sightings of diamond-shaped squid Thysanoteuthis rhombus
      egg masses in the Canary Islands (Atlantic Ocean) are presented. A total of 16
      egg masses of this species were recorded and photographed from 2000 to 2010
      around the western islands of the archipelago (El Hierro, Tenerife and La
      Gomera). These data reveal the existence of an important spawning area for
      diamond-shaped squid around the Canary Islands, in subtropical east Atlantic
      waters. We provide preliminary data for the potential development of an artisanal
      fishery focused on this species, and a discussion on its potential impacts on the
      marine ecosystem.

PMID- 23129988
TI  - A revision and phylogenetic analysis of Stoiba Spaeth 1909 (Coleoptera,
      Chrysomelidae).
AB  - Stoiba Spaeth, 1909 is revised with a phylogenetic analysis of 38 adult
      morphological characters for nine Stoiba species and 11 outgroup species
      (Mesomphaliini, Ischyrosonychini, and Hemisphaerotini). Four Cuban species of
      Stoiba were not sampled. Parsimony analysis located the four most parsimonious
      trees. The strict consensus (CI=0.59, RI=0.78, Steps=83) resolved the monophyly
      of Stoiba. The monophyly of Stoiba is supported by pale yellow antennae,
      antennomere VII broader than its length, and rounded basal line of pronotum. An
      illustrated key to ten species of Stoiba is provided along with a distribution
      map of 11 species. Stoiba rufa Blake is synonymized with Stoiba swartzii
      (Thunberg) by a morphological comparison which includes female genitalia.

PMID- 23129989
TI  - The first precinctive Carabidae from Moorea, Society Islands: new Mecyclothorax
      spp. (Coleoptera) from the summit of Mont Tohiea.
AB  - Seven species of Mecyclothorax Sharp from Moorea, Society Islands are newly
      described; Mecyclothorax perraultisp. n., Mecyclothorax paheresp. n.,
      Mecyclothorax menemenesp. n., Mecyclothorax mahatahisp. n., Mecyclothorax
      popotioaoasp. n., Mecyclothorax maposp. n., and Mecyclothorax fatatasp. n. These
      constitute the first Mecyclothorax species described from Moorea, and the first
      carabid beetle species shown to be geographically restricted to that island. Each
      of the newly described species is most similar to a different species on the
      island of Tahiti, suggesting that none of the seven Moorean taxa are evolutionary
      end-products of autochthonous speciation within Moorea. The occurrence of
      precinctive Mecyclothorax species on both Moorea and Tahiti demonstrates that
      radiation of Mecyclothorax in the Society Islands has been facilitated by
      speciation events implicating both islands. Whether this speciation has been
      preceded by vicariance or dispersal is discussed, with the generality of a
      dispersal hypothesis tested using information from Society Island Nabidae
      (Hemiptera). Salient morphological characters for taxa in the Society and
      Hawaiian Islands are compared to those representing a broad survey of southwest
      Pacific Mecyclothorax spp. This comparison supports the independent founding of
      each radiation in the Societies and Hawaii from an Australian ancestral
      propagule, likely drawn from the ecologically general, geographically widespread
      Mecyclothorax punctipennis (Macleay).

PMID- 23129990
TI  - A new species of Angelopteromyia Korneyev, 2001 (Diptera, Platystomatidae) from
      Iran, with the key to the species.
AB  - Angelopteromyia korneyevi Mohamadzade Namin, sp. n. from Iran is described and
      figured. The new species is similar to other species of Angelopteromyia in having
      abdominal spiracles 5 of females not approximated medially, as well as clypeus
      extended postero-ventrally, antenna shorter than face, and R(1) and R(4+5)
      setulose on dorsal side. It differs from other species of Angelopteromyia by
      having mostly brown wing with 3 hyaline crossbands and a few hyaline spots, and
      dark brownish basal and costal cells without hyaline spots.

PMID- 23129991
TI  - Description of a new species of Calliostoma (Gastropoda, Calliostomatidae) from
      Southeastern Brazil.
AB  - Calliostoma tupinamba isa new species from Southeastern Brazil, ranging from
      southern Rio de Janeiro to northern Sao Paulo, and found only on coastal islands,
      on rocks and sessile invertebrates at 3 to 5 meters of depth. Shell and soft part
      morphology is described here in detail. Calliostoma tupinamba is mainly
      characterized by a depressed trochoid shell; eight slightly convex whorls; a
      sharply suprasutural carina starting on the third whorl and forming a peripheral
      rounded keel; and a whitish, funnel-shaped and deep umbilicus, measuring about 5%
      10% of maximum shell width. Calliostoma tupinamba resembles Calliostoma bullisi
      Clench & Turner, 1960 in shape, but differs from it in being taller and wider,
      having a smaller umbilicus and lacking a strong and large innermost spiral cord
      at its base. Finally, an identification key of Brazilian Calliostoma species is
      presented.

PMID- 23129992
TI  - Increasing the Trapping Mass Range to m/z = 10(9)-A Major Step Toward High
      Resolution Mass Analysis of Intact RNA, DNA and Viruses.
AB  - This work demonstrates sampling of singly-charged particles up to 200 nm in
      diameter at atmospheric pressure into vacuum and trapping large numbers (>10(6))
      at a point in front of the end cap electrode of a linear quadrupole ion
      guide/trap for on-demand injection into the acceleration region of a time-of
      flight mass spectrometer in a well-collimated ion packet. This procedure was
      shown to yield trapping efficiencies that ranged from 4-5 percent for 10 nm
      diameter urea particles (~ 400 kDa) to 1 percent for 200 nm urea particles (~ 3 *
      10(9) Da). Analysis of the inlet optimization procedure suggests that the inlet
      can be adapted to sample and trap beyond the 200 nm range. Review of the most
      likely places for ion loss in the sampling process suggests that the sampling and
      trapping efficiencies can be improved well beyond the 4-5 percent shown.
      Moreover, it suggests that sampling of smaller than 10 nm ions could achieve
      efficiencies in the 10's of percent range thereby suggesting new levels of
      sensitivity can be achieved for small ions (< 200 kDa). Finally, demonstration of
      trapping large numbers of 200 nm (3 * 10(9) Da) ions for on-demand ejection in
      well collimated temporally discrete ion packets is a prelude to resolved mass
      analysis in that range.

PMID- 23129993
TI  - Toward an affective neuroscience account of financial risk taking.
AB  - To explain human financial risk taking, economic, and finance theories typically
      refer to the mathematical properties of financial options, whereas psychological
      theories have emphasized the influence of emotion and cognition on choice. From a
      neuroscience perspective, choice emanates from a dynamic multicomponential
      process. Recent technological advances in neuroimaging have made it possible for
      researchers to separately visualize perceptual input, intermediate processing,
      and motor output. An affective neuroscience account of financial risk taking thus
      might illuminate affective mediators that bridge the gap between statistical
      input and choice output. To test this hypothesis, we conducted a quantitative
      meta-analysis (via activation likelihood estimate or ALE) of functional magnetic
      resonance imaging experiments that focused on neural responses to financial
      options with varying statistical moments (i.e., mean, variance, skewness).
      Results suggested that different statistical moments elicit both common and
      distinct patterns of neural activity. Across studies, high versus low mean had
      the highest probability of increasing ventral striatal activity, but high versus
      low variance had the highest probability of increasing anterior insula activity.
      Further, high versus low skewness had the highest probability of increasing
      ventral striatal activity. Since ventral striatal activity has been associated
      with positive aroused affect (e.g., excitement), whereas anterior insular
      activity has been associated with negative aroused affect (e.g., anxiety) or
      general arousal, these findings are consistent with the notion that statistical
      input influences choice output by eliciting anticipatory affect. The findings
      also imply that neural activity can be used to predict financial risk taking -
      both when it conforms to and violates traditional models of choice.

PMID- 23129995
TI  - Memory and motivational/emotional processes.

PMID- 23129994
TI  - A computational model of inferior colliculus responses to amplitude modulated
      sounds in young and aged rats.
AB  - The inferior colliculus (IC) receives ascending excitatory and inhibitory inputs
      from multiple sources, but how these auditory inputs converge to generate IC
      spike patterns is poorly understood. Simulating patterns of in vivo spike train
      data from cellular and synaptic models creates a powerful framework to identify
      factors that contribute to changes in IC responses, such as those resulting in
      age-related loss of temporal processing. A conductance-based single neuron IC
      model was constructed, and its responses were compared to those observed during
      in vivo IC recordings in rats. IC spike patterns were evoked using amplitude
      modulated tone or noise carriers at 20-40 dB above threshold and were classified
      as low-pass, band-pass, band-reject, all-pass, or complex based on their rate
      modulation transfer function tuning shape. Their temporal modulation transfer
      functions were also measured. These spike patterns provided experimental measures
      of rate, vector strength, and firing pattern for comparison with model outputs.
      Patterns of excitatory and inhibitory synaptic convergence to IC neurons were
      based on anatomical studies and generalized input tuning for modulation
      frequency. Responses of modeled ascending inputs were derived from experimental
      data from previous studies. Adapting and sustained IC intrinsic models were
      created, with adaptation created via calcium-activated potassium currents. Short
      term synaptic plasticity was incorporated into the model in the form of synaptic
      depression, which was shown to have a substantial effect on the magnitude and
      time course of the IC response. The most commonly observed IC response sub-types
      were recreated and enabled dissociation of inherited response properties from
      those that were generated in IC. Furthermore, the model was used to make
      predictions about the consequences of reduction in inhibition for age-related
      loss of temporal processing due to a reduction in GABA seen anatomically with
      age.

PMID- 23129996
TI  - Neuronal signaling and behavior.

PMID- 23129997
TI  - Bi-directional astrocytic regulation of neuronal activity within a network.
AB  - The concept of a tripartite synapse holds that astrocytes can affect both the pre
      and post-synaptic compartments through the Ca(2+)-dependent release of
      gliotransmitters. Because astrocytic Ca(2+) transients usually last for a few
      seconds, we assumed that astrocytic regulation of synaptic transmission may also
      occur on the scale of seconds. Here, we considered the basic physiological
      functions of tripartite synapses and investigated astrocytic regulation at the
      level of neural network activity. The firing dynamics of individual neurons in a
      spontaneous firing network was described by the Hodgkin-Huxley model. The neurons
      received excitatory synaptic input driven by the Poisson spike train with
      variable frequency. The mean field concentration of the released neurotransmitter
      was used to describe the presynaptic dynamics. The amplitudes of the excitatory
      postsynaptic currents (PSCs) obeyed the gamma distribution law. In our model,
      astrocytes depressed the presynaptic release and enhanced the PSCs. As a result,
      low frequency synaptic input was suppressed while high frequency input was
      amplified. The analysis of the neuron spiking frequency as an indicator of
      network activity revealed that tripartite synaptic transmission dramatically
      changed the local network operation compared to bipartite synapses. Specifically,
      the astrocytes supported homeostatic regulation of the network activity by
      increasing or decreasing firing of the neurons. Thus, the astrocyte activation
      may modulate a transition of neural network into bistable regime of activity with
      two stable firing levels and spontaneous transitions between them.

PMID- 23129998
TI  - Supercomputers ready for use as discovery machines for neuroscience.
AB  - NEST is a widely used tool to simulate biological spiking neural networks. Here
      we explain the improvements, guided by a mathematical model of memory
      consumption, that enable us to exploit for the first time the computational power
      of the K supercomputer for neuroscience. Multi-threaded components for wiring and
      simulation combine 8 cores per MPI process to achieve excellent scaling. K is
      capable of simulating networks corresponding to a brain area with 10(8) neurons
      and 10(12) synapses in the worst case scenario of random connectivity; for larger
      networks of the brain its hierarchical organization can be exploited to constrain
      the number of communicating computer nodes. We discuss the limits of the software
      technology, comparing maximum filling scaling plots for K and the JUGENE BG/P
      system. The usability of these machines for network simulations has become
      comparable to running simulations on a single PC. Turn-around times in the range
      of minutes even for the largest systems enable a quasi interactive working style
      and render simulations on this scale a practical tool for computational
      neuroscience.

PMID- 23129999
TI  - Sequential Loss of LC Noradrenergic and Dopaminergic Neurons Results in a
      Correlation of Dopaminergic Neuronal Number to Striatal Dopamine Concentration.
AB  - Noradrenergic neurons in the locus coeruleus (LC) are significantly reduced in
      Parkinson's disease (PD) and the LC exhibits neuropathological changes early in
      the disease process. It has been suggested that a loss of LC neurons can enhance
      the susceptibility of dopaminergic neurons to damage. To determine if LC
      noradrenergic innervation protects dopaminergic neurons from damage, the
      dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was
      administered to adult male C57Bl/6 mice 3 days after bilateral LC administration
      of 6-hydroxydopamine (6OHDA), a time when there is a significant reduction in LC
      neuronal number and innervation to forebrain regions. To assess if LC loss can
      affect dopaminergic loss four groups of animals were studied: control, 6OHDA,
      MPTP, and 6OHDA + MPTP; animals sacrificed 3 weeks after MPTP administration. The
      number of dopaminergic neurons in the substantia nigra (SN) and ventral tegmental
      area (VTA), and noradrenergic neurons in the LC were determined. Catecholamine
      levels in striatum were measured by high-pressure liquid chromatography. The loss
      of LC neurons did not affect the number of dopaminergic neurons in the SN and VTA
      compared to control; however, LC 6OHDA significantly reduced striatal dopamine
      (DA; 29% reduced) but not norepinephrine (NE) concentration. MPTP significantly
      reduced SN and VTA neuronal number and DA concentration in the striatum compared
      to control; however, there was not a correlation of striatal DA concentration
      with SN or VTA neuronal number. Administration of 6OHDA prior to MPTP did not
      enhance MPTP-induced damage despite an effect of LC loss on striatal DA
      concentration. However, the loss of LC neurons before MPTP resulted now in a
      correlation between SN and VTA neuronal number to striatal DA concentration.
      These results demonstrate that the loss of either LC or DA neurons can affect the
      function of each others systems, indicating the importance of both the
      noradrenergic and dopaminergic system in PD.

PMID- 23130000
TI  - Left and right brain-oriented hemisity subjects show opposite behavioral
      preferences.
AB  - INTRODUCTION: Recently, three independent, intercorrelated biophysical measures
      have provided the first quantitative measures of a binary form of behavioral
      laterality called "Hemisity," a term referring to inherent opposite right or left
      brain-oriented differences in thinking and behavioral styles. Crucially, the
      right or left brain-orientation of individuals assessed by these methods was
      later found to be essentially congruent with the thicker side of their ventral
      gyrus of the anterior cingulate cortex (vgACC) as revealed by a 3 min MRI
      procedure. Laterality of this putative executive structural element has thus
      become the primary standard defining individual hemisity. METHODS: Here, the
      behavior of 150 subjects, whose hemisity had been calibrated by MRI, was assessed
      using five MRI-calibrated preference questionnaires, two of which were new.
      RESULTS: Right and left brain-oriented subjects selected opposite answers (p >
      0.05) for 47 of the 107 "either-or," forced choice type preference questionnaire
      items. The resulting 30 hemisity subtype preference differences were present in
      several areas. These were: (1) in logical orientation, (2) in type of
      consciousness, (3) in fear level and sensitivity, (4) in social-professional
      orientation, and (5) in pair bonding-spousal dominance style. CONCLUSIONS: The
      right and left brain-oriented hemisity subtype subjects, sorted on the anatomical
      basis of upon which brain side their vgACC was thickest, showed 30 significant
      differences in their "either-or" type of behavioral preferences.

PMID- 23130001
TI  - From quiescence to proliferation: Cdk oscillations drive the mammalian cell
      cycle.
AB  - We recently proposed a detailed model describing the dynamics of the network of
      cyclin-dependent kinases (Cdks) driving the mammalian cell cycle (Gerard and
      Goldbeter, 2009). The model contains four modules, each centered around one
      cyclin/Cdk complex. Cyclin D/Cdk4-6 and cyclin E/Cdk2 promote progression in G1
      and elicit the G1/S transition, respectively; cyclin A/Cdk2 ensures progression
      in S and the transition S/G2, while the activity of cyclin B/Cdk1 brings about
      the G2/M transition. This model shows that in the presence of sufficient amounts
      of growth factor the Cdk network is capable of temporal self-organization in the
      form of sustained oscillations, which correspond to the ordered, sequential
      activation of the various cyclin/Cdk complexes that control the successive phases
      of the cell cycle. The results suggest that the switch from cellular quiescence
      to cell proliferation corresponds to the transition from a stable steady state to
      sustained oscillations in the Cdk network. The transition depends on a finely
      tuned balance between factors that promote or hinder progression in the cell
      cycle. We show that the transition from quiescence to proliferation can occur in
      multiple ways that alter this balance. By resorting to bifurcation diagrams, we
      analyze the mechanism of oscillations in the Cdk network. Finally, we show that
      the complexity of the detailed model can be greatly reduced, without losing its
      key dynamical properties, by considering a skeleton model for the Cdk network.
      Using such a skeleton model for the mammalian cell cycle we show that positive
      feedback (PF) loops enhance the amplitude and the robustness of Cdk oscillations
      with respect to molecular noise. We compare the relative merits of the detailed
      and skeleton versions of the model for the Cdk network driving the mammalian cell
      cycle.

PMID- 23130002
TI  - Immediate effects of tDCS on the MU-opioid system of a chronic pain patient.
AB  - We developed a unique protocol where transcranial direct current stimulation
      (tDCS) of the motor cortex is performed during positron emission tomography (PET)
      scan using a MU-opioid receptor (MUOR) selective radiotracer, [(11)C]carfentanil.
      This is one of the most important central neuromechanisms associated with pain
      perception and regulation. We measured MUOR non-displaceable binding potential
      (MUOR BP(ND)) in a trigeminal neuropathic pain patient (TNP) without creating
      artifacts, or posing risks to the patient (e.g., monitoring of resistance). The
      active session directly improved in 36.2% the threshold for experimental cold
      pain in the trigeminal allodynic area, mandibular branch, but not the TNP
      patient's clinical pain. Interestingly, the single active tDCS application
      considerably decreased MUORBP(ND) levels in (sub)cortical pain-matrix structures
      compared to sham tDCS, especially in the posterior thalamus. Suggesting that the
      MU-opioidergic effects of a single tDCS session are subclinical at immediate
      level, and repetitive sessions are necessary to revert ingrained neuroplastic
      changes related to the chronic pain. To our knowledge, we provide data for the
      first time in vivo that there is possibly an instant increase of endogenous MU
      opioid release during acute motor cortex neuromodulation with tDCS.

PMID- 23130003
TI  - Do Left and Right have Temporal Meaning?

PMID- 23130004
TI  - Infants' learning of phonological status.
AB  - There is a substantial literature describing how infants become more sensitive to
      differences between native phonemes (sounds that are both present and meaningful
      in the input) and less sensitive to differences between non-native phonemes
      (sounds that are neither present nor meaningful in the input) over the course of
      development. Here, we review an emergent strand of literature that gives a more
      nuanced notion of the problem of sound category learning. This research documents
      infants' discovery of phonological status, signaled by a decrease in sensitivity
      to sounds that map onto the same phonemic category vs. different phonemic
      categories. The former phones are present in the input, but their difference does
      not cue meaning distinctions because they are tied to one and the same phoneme.
      For example, the diphthong I in I'm should map to the same underlying category as
      the diphthong in I'd, despite the fact that the first vowel is nasal and the
      second oral. Because such pairs of sounds are processed differently than those
      than map onto different phonemes by adult speakers, the learner has to come to
      treat them differently as well. Interestingly, there is some evidence that
      infants' sensitivity to dimensions that are allophonic in the ambient language
      declines as early as 11 months. We lay out behavioral research, corpora analyses,
      and computational work which sheds light on how infants achieve this feat at such
      a young age. Collectively, this work suggests that the computation of
      complementary distribution and the calculation of phonetic similarity operate in
      concert to guide infants toward a functional interpretation of sounds that are
      present in the input, yet not lexically contrastive. In addition to reviewing
      this literature, we discuss broader implications for other fundamental
      theoretical and empirical questions.

PMID- 23130005
TI  - On the influence of reward on action-effect binding.
AB  - Ideomotor theory states that the formation of anticipatory representations about
      the perceptual consequences of an action [i.e., action-effect (A-E) binding]
      provides the functional basis of voluntary action control. A host of studies have
      demonstrated that A-E binding occurs fast and effortlessly, yet little is known
      about cognitive and affective factors that influence this learning process. In
      the present study, we sought to test whether the motivational value of an action
      modulates the acquisition of A-E associations. To this end, we linked specific
      actions with monetary incentives during the acquisition of novel A-E mappings. In
      a subsequent test phase, the degree of binding was assessed by presenting the
      former effect stimuli as task-irrelevant response primes in a forced-choice
      response task, absent reward. Binding, as indexed by response priming through the
      former action-effects, was only found for reward-related A-E mappings. Moreover,
      the degree to which reward associations modulated the binding strength was
      predicted by individuals' trait sensitivity to reward. These observations
      indicate that the association of actions and their immediate outcomes depends on
      the motivational value of the action during learning, as well as on the
      motivational disposition of the individual. On a larger scale, these findings
      also highlight the link between ideomotor theories and reinforcement-learning
      theories, providing an interesting perspective for future research on
      anticipatory regulation of behavior.

PMID- 23130006
TI  - Self-controlled learning: the importance of protecting perceptions of competence.
AB  - Recent studies examining the role of self-controlled feedback have shown that
      learners ask for feedback after what they believe was a "good" rather than "poor"
      trial. Also, trials on which participants request feedback are often more
      accurate than those without feedback. The present study examined whether
      manipulating participants' perception of "good" performance would have
      differential effects on learning. All participants practiced a coincident
      anticipation timing task with a self-controlled feedback schedule during
      practice. Specifically, they were able to ask for feedback after 3 trials in each
      of three 10-trial practice blocks. While one group (Self-30) was told that an
      error of 30 ms or less would be considered good performance, another group (Self
      4) was informed that an error of 4 ms or less would be considered a good trial. A
      third, self-control group (Self) did not receive any information about what
      constituted good performance. The results showed that participants of all groups
      asked for feedback primarily after relatively good trials. At the end of
      practice, both the Self-30 and Self groups demonstrated greater perceived
      competence and self-efficacy than the Self-4 group. The Self-30 and Self groups
      also performed with greater accuracy and less variability in retention and
      transfer (non-dominant hand) 1 day later. The present findings indicated that the
      typical learning benefits of self-controlled practice can be thwarted by
      depriving learners of the opportunity of experiencing competence through good
      performance. They add to the accumulating evidence of motivational influences on
      motor learning.

PMID- 23130007
TI  - When Do We Confuse Self and Other in Action Memory? Reduced False Memories of
      Self-Performance after Observing Actions by an Out-Group vs. In-Group Actor.
AB  - Observing another person performing an action can lead to a false memory of
      having performed the action oneself - the observation-inflation effect. In the
      experimental paradigm, participants first perform or do not perform simple
      actions, and then observe another person perform some of these actions. The
      observation-inflation effect is found when participants later remember performing
      actions that they have merely observed. In this case, self and other are confused
      in action memory. We examined social conditions of this self-other confusion when
      remembering actions, specifically whether the effect depends on the observed
      actor's group membership. In our experiment, we manipulated group membership
      based on physical appearance, specifically complexion of the hands. Fair-skinned
      participants observed either an in-group (i.e., fair-skinned) or an out-group
      (i.e., dark-skinned) actor. Our results revealed that the observed actor's group
      membership moderated the observation-inflation effect: False memories were
      significantly reduced when the actor was from the out-group (vs. in-group). We
      found no difference to a control condition in which the actor wore black gloves,
      suggesting that distinctiveness of perceptual or sensory features alone (due to
      the out-group member's dark skin) is not critical. We discuss these findings in
      light of social-neuroscience studies demonstrating the impact of an observed
      person's group membership on motor simulation. Overall, our findings suggest that
      action memory can be affected by a ubiquitous feature of people's social
      perception, that is, group-based social categorization of others.

PMID- 23130008
TI  - The Movement Kinematics and Learning Strategies Associated with Adopting
      Different Foci of Attention during Both Acquisition and Anxious Performance.
AB  - Research suggests that implicit strategies adopted during learning help prevent
      breakdown of automatic processes and subsequent performance decrements associated
      with the presence of pressure. According to the Constrained Action Hypothesis,
      automaticity of movement is promoted when adopting an external focus of
      attention. The purpose of the current experiment was to investigate if learning
      with an external focus of attention can enhance performance under subsequent
      pressure situations through promoting implicit learning and automaticity. Since
      previous research has generally used outcome measures of performance, the current
      study adopted measures of movement production. Specifically, we calculated within
      subject variability in trajectory velocity and distance traveled every 10% of
      movement time. This detailed kinematic analysis allowed investigation into some
      of the previously unexplored mechanisms responsible for the benefits of adopting
      an external focus of attention. Novice participants performed a 2.5 m golf putt.
      Following a pre-test, participants were randomly assigned to one of three focus
      groups (internal, external, control). Participants then completed 400 acquisition
      trials over two consecutive days before being subjected to both a low anxiety and
      high anxiety (HA) transfer test. Dependent variables included variability, number
      of successful putts and mean radial error. Results revealed that variability was
      greater in the internal compared to the external and control groups. Putting
      performance revealed that all groups increased performance following acquisition.
      However, only the control group demonstrated a decrement in performance in the HA
      transfer test. These findings suggest that adopting an appropriate focus of
      attention during learning can prevent choking; with an external focus inhibiting
      the breakdown of automatic processes and an internal focus acting as a self-focus
      learning strategy and thus desensitizing individuals to anxiety effects.

PMID- 23130009
TI  - Subitizing and visual short-term memory in human and non-human species: a common
      shared system?

PMID- 23130010
TI  - A neural model for temporal order judgments and their active recalibration: a
      common mechanism for space and time?
AB  - When observers experience a constant delay between their motor actions and
      sensory feedback, their perception of the temporal order between actions and
      sensations adapt (Stetson et al., 2006). We present here a novel neural model
      that can explain temporal order judgments (TOJs) and their recalibration. Our
      model employs three ubiquitous features of neural systems: (1) information
      pooling, (2) opponent processing, and (3) synaptic scaling. Specifically, the
      model proposes that different populations of neurons encode different delays
      between motor-sensory events, the outputs of these populations feed into rivaling
      neural populations (encoding "before" and "after"), and the activity difference
      between these populations determines the perceptual judgment. As a consequence of
      synaptic scaling of input weights, motor acts which are consistently followed by
      delayed sensory feedback will cause the network to recalibrate its point of
      subjective simultaneity. The structure of our model raises the possibility that
      recalibration of TOJs is a temporal analog to the motion aftereffect (MAE). In
      other words, identical neural mechanisms may be used to make perceptual
      determinations about both space and time. Our model captures behavioral
      recalibration results for different numbers of adapting trials and different
      adapting delays. In line with predictions of the model, we additionally
      demonstrate that temporal recalibration can last through time, in analogy to
      storage of the MAE.

PMID- 23130011
TI  - Faces in context: a review and systematization of contextual influences on
      affective face processing.
AB  - Facial expressions are of eminent importance for social interaction as they
      convey information about other individuals' emotions and social intentions.
      According to the predominant "basic emotion" approach, the perception of emotion
      in faces is based on the rapid, automatic categorization of prototypical,
      universal expressions. Consequently, the perception of facial expressions has
      typically been investigated using isolated, de-contextualized, static pictures of
      facial expressions that maximize the distinction between categories. However, in
      everyday life, an individual's face is not perceived in isolation, but almost
      always appears within a situational context, which may arise from other people,
      the physical environment surrounding the face, as well as multichannel
      information from the sender. Furthermore, situational context may be provided by
      the perceiver, including already present social information gained from affective
      learning and implicit processing biases such as race bias. Thus, the perception
      of facial expressions is presumably always influenced by contextual variables. In
      this comprehensive review, we aim at (1) systematizing the contextual variables
      that may influence the perception of facial expressions and (2) summarizing
      experimental paradigms and findings that have been used to investigate these
      influences. The studies reviewed here demonstrate that perception and neural
      processing of facial expressions are substantially modified by contextual
      information, including verbal, visual, and auditory information presented
      together with the face as well as knowledge or processing biases already present
      in the observer. These findings further challenge the assumption of automatic,
      hardwired categorical emotion extraction mechanisms predicted by basic emotion
      theories. Taking into account a recent model on face processing, we discuss where
      and when these different contextual influences may take place, thus outlining
      potential avenues in future research.

PMID- 23130012
TI  - When does perception facilitate or interfere with conceptual processing? The
      effect of attentional modulation.

PMID- 23130013
TI  - Emotional mimicry in social context: the case of disgust and pride.
AB  - A recent review on facial mimicry concludes that emotional mimicry is less
      ubiquitous than has been suggested, and only occurs in interactions that are
      potentially affiliative (see Hess and Fischer, in revision). We hypothesize that
      individuals do not mimic facial expressions that can be perceived as offensive,
      such as disgust, and mimic positive emotion displays, but only when the context
      is affiliative (i.e., with intimates). Second, we expect that in spontaneous
      interactions not mimicry, but empathic feelings with the other predict the
      accurateness of emotion recognition. Data were collected in a pseudo-experimental
      setting, during an event organized for subscribers of a large Dutch women's
      magazine. One woman (expresser) was exposed to two emotional stimuli (i.e., a
      vile smell, a compliment) in order to evoke disgust and pride respectively.
      Another woman (observer: intimate or stranger) was sitting opposite of her. We
      collected self-report measures on emotions and empathy, and coded facial
      expressions of disgust and smiling on the basis of FACS. The results show that
      participants do not mimic disgust. In contrast, smiles displayed after the vile
      smell and the compliment were mimicked, but only among intimates. We also found
      that self-reported empathy and not mimicry is related to the recognition of
      disgust. These findings are discussed in the light of a Social Contextual view on
      emotional mimicry.

PMID- 23130014
TI  - Cognitive and affective control.

PMID- 23130015
TI  - Biomarkers of hypoxic-ischemic encephalopathy in newborns.
AB  - As neonatal intensive care has evolved, the focus has shifted from improving
      mortality alone to an effort to improve both mortality and morbidity. The most
      frequent source of neonatal brain injury occurs as a result of hypoxic-ischemic
      injury. Hypoxic-ischemic injury occurs in about 2 of 1,000 full-term infants and
      severe injured infants will have lifetime disabilities and neurodevelopmental
      delays. Most recently, remarkable efforts toward neuroprotection have been
      started with the advent of therapeutic hypothermia and a key step in the
      evolution of neonatal neuroprotection is the discovery of biomarkers that enable
      the clinician-scientist to screen infants for brain injury, monitor progression
      of disease, identify injured brain regions, and assess efficacy of
      neuroprotective clinical trials. Lastly, biomarkers offer great hope identifying
      when an injury occurred shedding light on the potential pathophysiology and the
      most effective therapy. In this article, we will review biomarkers of HIE
      including S100B, neuron specific enolase, umbilical cord IL-6, CK-BB, GFAP,
      myelin basic protein, UCHL-1, and pNF-H. We hope to contribute to the awareness,
      validation, and clinical use of established as well as novel neonatal brain
      injury biomarkers.

PMID- 23130017
TI  - Nitrogenase (nifH) gene expression in diazotrophic cyanobacteria in the Tropical
      North Atlantic in response to nutrient amendments.
AB  - The Tropical North Atlantic (TNAtl) plays a critical role in the marine nitrogen
      cycle, as it supports high rates of biological nitrogen (N(2)) fixation, yet it
      is unclear whether this process is limited by the availability of iron (Fe),
      phosphate (P) or is co-limited by both. In order to investigate the impact of
      nutrient limitation on the N(2)-fixing microorganisms (diazotrophs) in the TNAtl,
      trace metal clean nutrient amendment experiments were conducted, and the
      expression of nitrogenase (nifH) in cyanobacterial diazotrophs in response to the
      addition of Fe, P, or Fe+P was measured using quantitative PCR. To provide
      context, N(2) fixation rates associated with the <10 MUm community and diel nifH
      expression in natural cyanobacterial populations were measured. In the western
      TNAtl, nifH expression in Crocosphaera, Trichodesmium, and Richelia was
      stimulated by Fe and Fe+P additions, but not by P, implying that diazotrophs may
      be Fe-limited in this region. In the eastern TNAtl, nifH expression in
      unicellular cyanobacteria UCYN-A and Crocosphaera was stimulated by P, implying P
      limitation. In equatorial waters, nifH expression in Trichodesmium was highest in
      Fe+P treatments, implying co-limitation in this region. Nutrient additions did
      not measurably stimulate N(2) fixation rates in the <10 MUm fraction in most of
      the experiments, even when upregulation of nifH expression was evident. These
      results demonstrate the utility of using gene expression to investigate the
      physiological state of natural populations of microorganisms, while underscoring
      the complexity of nutrient limitation on diazotrophy, and providing evidence that
      diazotroph populations are slow to respond to the addition of limiting nutrients
      and may be limited by different nutrients on basin-wide spatial scales. This has
      important implications for our current understanding of controls on N(2) fixation
      in the TNAtl and may partially explain why it appears to be intermittently
      limited by Fe, P, or both.

PMID- 23130016
TI  - Meta-type analysis of dopaminergic effects on gene expression in the
      neuroendocrine brain of female goldfish.
AB  - Dopamine (DA) is a major neurotransmitter important for neuroendocrine control
      and recent studies have described genomic signaling pathways activated and
      inhibited by DA agonists and antagonists in the goldfish brain. Here we perform a
      meta-type analysis using microarray datasets from experiments conducted with
      female goldfish to characterize the gene expression responses that underlie
      dopaminergic signaling. Sexually mature, pre-spawning [gonadosomatic index (GSI)
      = 4.5 +/- 1.3%] or sexually regressing (GSI = 3 +/- 0.4%) female goldfish (15-40
      g) injected intraperitoneally with either SKF 38393, LY 171555, SCH 23390,
      sulpiride, or a combination of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and
      alpha-methyl-p-tyrosine. Microarray meta-type analysis identified 268 genes in
      the telencephalon and hypothalamus as having reciprocal (i.e., opposite between
      agonism and antagonism/depletion) fold change responses, suggesting that these
      transcripts are likely targets for DA-mediated regulation. Noteworthy genes
      included ependymin, vimentin, and aromatase, genes that support the significance
      of DA in neuronal plasticity and tissue remodeling. Sub-network enrichment
      analysis (SNEA) was used to identify common gene regulators and binding proteins
      associated with the differentially expressed genes mediated by DA. SNEA analysis
      identified gene expression targets that were related to three major categories
      that included cell signaling (STAT3, SP1, SMAD, Jun/Fos), immune response (IL-6,
      IL-1beta, TNFs, cytokine, NF-kappaB), and cell proliferation and growth (IGF1,
      TGFbeta1). These gene networks are also known to be associated with
      neurodegenerative disorders such as Parkinsons' disease, well-known to be
      associated with loss of dopaminergic neurons. This study identifies genes and
      networks that underlie DA signaling in the vertebrate CNS and provides targets
      that may be key neuroendocrine regulators. The results provide a foundation for
      future work on dopaminergic regulation of gene expression in fish model systems.

PMID- 23130018
TI  - Isolation, Molecular Characterization, and Mapping of Four Rose MLO Orthologs.
AB  - Powdery mildew is a major disease of economic importance in cut and pot roses. As
      an alternative to conventional resistance breeding strategies utilizing single
      dominant genes or QTLs, mildew resistance locus o (MLO)-based resistance might
      offer some advantages. In dicots such as Arabidopsis, pea, and tomato, loss-of
      function mutations in MLO genes confer high levels of broad-spectrum resistance.
      Here, we report the isolation and characterization of four MLO homologs from a
      large rose EST collection isolated from leaves. These genes are phylogenetically
      closely related to other dicot MLO genes that are involved in plant powdery
      mildew interactions. Therefore, they are candidates for MLO genes involved in
      rose powdery mildew interactions. Two of the four isolated genes contain all of
      the sequence signatures considered to be diagnostic for MLO genes. We mapped all
      four genes to three linkage groups and conducted the first analysis of
      alternative alleles. This information is discussed in regards to a reverse
      genetics approach aimed at the selection of rose plants that are homozygous for
      loss-of-function in one or more MLO genes.

PMID- 23130019
TI  - Frequencies of 23 functionally significant variant alleles related with
      metabolism of antineoplastic drugs in the chilean population: comparison with
      caucasian and asian populations.
AB  - Cancer is a leading cause of death worldwide. The cancer incidence rate in Chile
      is 133.7/100,000 inhabitants and it is the second cause of death, after
      cardiovascular diseases. Most of the antineoplastic drugs are metabolized to be
      detoxified, and some of them to be activated. Genetic polymorphisms of drug
      metabolizing enzymes can induce deep changes in enzyme activity, leading to
      individual variability in drug efficacy and/or toxicity. The present research
      describes the presence of genetic polymorphisms in the Chilean population, which
      might be useful in public health programs for personalized treatment of cancer,
      and compares these frequencies with those reported for Asian and Caucasian
      populations, as a contribution to the evaluation of ethnic differences in the
      response to chemotherapy. We analyzed 23 polymorphisms in a group of 253
      unrelated Chilean volunteers from the general population. The results showed that
      CYP2A6*2, CYP2A6*3, CYP2D6*3, CYP2C19*3, and CYP3A4*17 variant alleles are
      virtually absent in Chileans. CYP1A1*2A allele frequency (0.37) is similar to
      that of Caucasians and higher than that reported for Japanese people. Allele
      frequencies for CYP3A5*3(0.76) and CYP2C9*3(0.04) are similar to those observed
      in Japanese people. CYP1A1*2C(0.32), CYP1A2*1F(0.77), CYP3A4*1B(0.06),
      CYP2D6*2(0.41), and MTHFR T(0.52) allele frequencies are higher than the observed
      either in Caucasian or in Japanese populations. Conversely, CYP2C19*2 allelic
      frequency (0.12), and genotype frequencies for GSTT1 null (0.11) and GSTM1 null
      (0.36) are lower than those observed in both populations. Finally, allele
      frequencies for CYP2A6*4(0.04), CYP2C8*3(0.06), CYP2C9*2(0.06), CYP2D6*4(0.12),
      CYP2E1*5B(0.14), CYP2E1*6(0.19), and UGT2B7*2(0.40) are intermediate in relation
      to those described in Caucasian and in Japanese populations, as expected
      according to the ethnic origin of the Chilean population. In conclusion, our
      findings support the idea that ethnic variability must be considered in the
      pharmacogenomic assessment of cancer pharmacotherapy, especially in mixed
      populations and for drugs with a narrow safety range.

PMID- 23130020
TI  - Current progress of RNA aptamer-based therapeutics.
AB  - Aptamers are single-stranded nucleic acids that specifically recognize and bind
      tightly to their cognate targets due to their stable three-dimensional structure.
      Nucleic acid aptamers have been developed for various applications, including
      diagnostics, molecular imaging, biomarker discovery, target validation,
      therapeutics, and drug delivery. Due to their high specificity and binding
      affinity, aptamers directly block or interrupt the functions of target proteins
      making them promising therapeutic agents for the treatment of human maladies.
      Additionally, aptamers that bind to cell surface proteins are well suited for the
      targeted delivery of other therapeutics, such as conjugated small interfering
      RNAs (siRNA) that induce RNA interference (RNAi). Thus, aptamer-siRNA chimeras
      may offer dual-functions, in which the aptamer inhibits a receptor function,
      while the siRNA internalizes into the cell to target a specific mRNA. This review
      focuses on the current progress and therapeutic potential of RNA aptamers,
      including the use of cell-internalizing aptamers as cell-type specific delivery
      vehicles for targeted RNAi. In particular, we discuss emerging aptamer-based
      therapeutics that provide unique clinical opportunities for the treatment various
      cancers and neurological diseases.

PMID- 23130021
TI  - In vitro evaluation of the antibacterial activity of three root canal sealers.
AB  - INTRODUCTION: Antibacterial activity is one of the desirable properties of an
      ideal sealer. This study aimed to compare the antimicrobial effect of three
      different sealers, i.e. resin (AH26), calcium hydroxide (Apexit) and zinc oxide
      eugenol (ZOE) based sealers. MATERIALS AND METHODS: Direct contact test with agar
      diffusion was used in this in vitro study. The freshly mixed sealers were AH26,
      Apexit and pure ZOE. They were prepared according to manufacturer's instruction
      and placed in prepared wells of 30 agar plates inoculated with Streptococcus (S)
      mutans and Prevotella (P) melaninogenicus (15 samples for each microorganism).
      All plates were incubated for 7 days (196 hours) at 37C under anaerobic
      conditions, and zones of inhibition were measured after 3 days, 5 days and 7
      days. The data were analyzed using Kruskal-Wallis and Friedman tests. RESULTS: In
      all determined intervals, the antibacterial activity of AH26 was significantly
      greater than other test materials (P<0.001). ZOE sealer had moderate effect on
      test microorganisms, whilst Apexit showed the lowest antibacterial activity on S.
      Mutans and no antibacterial activity on P. melaninogenicus. CONCLUSION: The
      ascending sequence of bacterial growth inhibition zones was as AH26>Pure
      ZOE>Apexit.

PMID- 23130022
TI  - Comparison of AH26 Physicochemical Properties with Two AH26/Antibiotic
      Combinations.
AB  - INTRODUCTION: The purpose of this study was to compare the setting time and post
      setting solubility, flow, film thickness and dimensional changes of AH26 root
      canal sealer with AH26-Antibiotic combination. MATERIALS AND METHODS: This study
      was performed according to British standard BS 6876 (2001) which tests the
      physicochemical properties of endodontic sealers. Three samples of each of tested
      materials including AH26 alone, AH26/amoxicillin and AH26/doxycycline were used
      to test each of the properties. They were prepared according to ISO protocols.
      RESULTS: The setting time of studied materials was 46 hours for AH26, 29 hours
      for AH26/amoxicillin, 49 hours for AH26/doxycycline. Flow test results were as
      follows, for AH 26, 15.6 mm; AH26/amoxicillin, 14.9 mm; AH26/doxycycline, 14.2
      mm. Film thickness was 0.024 mm in AH26, 0.0283 mm in AH26/amoxicillin, 0.0276 mm
      AH26/doxycycline. The solubility of AH26 was 0.0076%, AH26/amoxicillin, 0.0113%,
      and for AH26/doxycycline, 0.013 %. Dimensional changes following setting was 0.07
      mm, 2.6 mm, and 1.1 mm for AH 26, AH26/amoxicillin, and AH26/doxycycline,
      respectively. CONCLUSION: The physico-mechanical properties of AH26 antibiotic
      combinations were superior compared with AH26, with the exception of flow. Also,
      AH26/amoxicillin had a lower setting time than AH26. However, all values were
      within an acceptable range which conformed to ISO.

PMID- 23130023
TI  - Comparison of stresses induced by fiber post, parapost and casting post in root
      canals by photoelasticity method.
AB  - INTRODUCTION: Many studies have been performed to evaluate the stress
      distribution around endodontic posts; those which compared posts composed of
      different materials are rare. The aim of this study was to compare stresses
      induced in dentin by three structurally different posts using photoelasticity
      method. MATERIALS AND METHODS: Nine blocks of PSM-5 Photoelastic material with
      45*45*10 mm dimension were prepared. In each block, a canal 9 mm in length and
      0.8 mm in width was drilled. Blocks were divided into 3 groups of three each. In
      the first group, the canals were prepared for insertion of Fiber Post with 1.25
      mm width. In the second group, the canals were prepared for insertion of ParaPost
      with 1.25 mm width and the canals in the third group were prepared for casting
      post similar to the above samples. Casting Post pattern was made by Duralay resin
      and casted by Ni-Cr alloy. All posts were cemented in canals with Panavia cement.
      The stresses were evaluated in the polariscope under three different conditions:
      1) without load, 2) with 135 N vertical load, and 3) with 90 N oblique load (26
      degrees  inclination to post long axis). The fringe orders in the cervical,
      middle and apical regions of the posts were evaluated and compared with each
      other. RESULTS: Application of the vertical load induced a high stress
      concentration (FO=4) in the apical region of the ParaPost, while lower stress was
      observed in the middle (FO=2) and cervical region (FO=2+). Fiber Post and Casting
      Post showed even stress distribution (FO=2+). High stress concentration was
      detected with the application of oblique force in the cervical region of ParaPost
      (FO=5) and Casting Post (FO=3+). Fiber Posts fractured before reaching 90-N
      loading force. CONCLUSION: The stress distribution around Fiber Post and Casting
      Post were constant in comparison with ParaPost. Fiber Post with 1.25 mm width was
      not recommended in situations with high oblique stresses.

PMID- 23130024
TI  - Comparison of bacterial and dye microleakage of different root-end filling
      materials.
AB  - INTRODUCTION: The provision of an effective apical seal is an essential factor
      when choosing an appropriate material for success of root-end surgeries. Root-end
      resection, preparation and obturation should provide an adequate apical seal. The
      aim of this in vitro study was to investigate bacterial and dye microleakage of
      four different root-end filling materials and compare the efficacy of these two
      methods. MATERIALS AND METHODS: Fifty-six single-rooted teeth with intact and
      straight roots were randomly assigned into four study groups of 12 each and two
      control groups of three each. After decoronation, root canals were prepared up to
      file size #40 using step back technique; then, they were filled with gutta-percha
      and AH26 sealer. Root-ends were resected 3 mm above the root-end and 3 mm deep
      cavities were prepared. Root-end cavities were filled with amalgam, Root Mineral
      Trioxide Aggregate (Root MTA), White ProRoot MTA (WMTA), and calcium enriched
      mixture (CEM) cement. Bacterial leakage was investigated in Trypticase Soy Broth
      (containing Enterococcus faecalis) after 70 days and 1% methylene blue dye
      leakage was assessed after 72 hours. Complete dye leakage was checked using
      stereomicroscope (*40). Data were statistically analyzed using Fisher Exact test.
      For pair comparison between the two methods Kapa agreement was utilized. RESULTS:
      After 70 days there was 100% bacterial leakage in amalgam, and CEM cement, 91.7%
      in WMTA, and 75% in Root MTA. This difference was not significantly different.
      The difference in complete dye leakage was also not significant (WMTA and CEM
      cement 16.7%, Amalgam and Root MTA 33.3%). CONCLUSION: There was no significant
      measure of agreement between dye and bacterial penetration along root-end
      fillings. CEM cement was not significantly different from currently used
      retrofilling materials e.g. WMTA.

PMID- 23130025
TI  - In vitro detection of simulated apical root perforation with two electronic apex
      locators.
AB  - INTRODUCTION: The aim of this study was to evaluate the accuracy of two
      electronic apex locators (Smarpex and NovApex) in detecting apical perforation.
      MATERIALS AND METHODS: After access cavity preparations, the working length was
      determined by the first examiner before and after perforation with a
      stereomicroscope by introducing a K-file size 10 into the canal and size 25 K
      file up to the perforation site, respectively. The specimens were embedded in a
      17-well plastic box containing alginate. The root canals were irrigated with
      chlorhexidine 0.2% (CHX) through a 27-gauge needle. Two examiners measured the
      root canal length twice and the mean value was calculated. The data were analyzed
      using Kolmogorov-Smirnov and ANOVA tests. RESULTS: The results obtained with each
      Electronic Apex Locator were compared with the corresponding control length. The
      statistical analysis showed reliable accuracies in detecting the perforation site
      for the two experimental electronic apex locators (60% and 80% for NovApex and
      Smarpex, respectively). CONCLUSION: Although no significant difference was shown
      between Smarpex and NovApex, these results suggest that electronic apex locators
      can effectively and reproducibly detect root canal perforations.

PMID- 23130026
TI  - Direct pulp-capping with calcium enriched mixture in primary molar teeth: a
      randomized clinical trial.
AB  - INTRODUCTION: The aim of this trial was to compare clinical and radiographic
      success rates of direct pulp capping (DPC) using a novel biomaterial called
      Calcium Enriched Mixture (CEM) cement versus Mineral Trioxide Aggregate (MTA) in
      primary molar teeth. MATERIALS AND METHODS: In this randomized clinical trial 42
      deciduous molars in 21 patients who had at least two teeth requiring DPC, were
      treated. The enrolled patients were between 5-8 years. The molar teeth were
      randomly divided into two experimental groups. Patients and operators were
      blinded. The teeth were anaesthetized, caries were removed and after pinpoint
      exposure of dental pulp, haemostasis was achieved. The exposure points were
      capped with MTA or CEM cement. All teeth were restored with amalgam. Patients
      were recalled for the 6-month follow up. Statistical analysis was carried out
      using McNemar test. RESULTS: Thirty-eight teeth were available for follow up (19
      in each group). The radiographic evaluations did not show failure in experimental
      groups; however, in clinical examinations one sinus tract was found in CEM cement
      group. Clinical success rates in CEM cement and MTA groups were 94.8% and 100%,
      respectively. Dentinal bridge formation was not observed in the two experimental
      groups. CONCLUSION: There is no significant difference between treatment outcomes
      of direct pulp capping with either CEM cement or MTA; therefore, both
      biomaterials can be used successfully for DPC in primary molar teeth.

PMID- 23130027
TI  - In vitro scanning electron microscopic study on the effect of doxycycline and
      vancomycin on enterococcal induced biofilm.
AB  - INTRODUCTION: Enterococcus (E) faecalis bacteria adhere to dentine of teeth root
      canals to form the biofilm. E. faecalis has been shown to be resistant to
      antibiotics. This in vitro study aimed to investigate the efficacy of vancomycin
      and doxycycline in inhibiting E. faecalis biofilm formation. MATERIALS AND
      METHODS: A total of 60 extracted human teeth were incubated with E. faecalis
      (ATCC 35550 strain) for 45 days to allow biofilm formation. The teeth were
      equally divided into six groups (n=10): 1) positive control, 2) negative control,
      3) doxycycline alone 4) doxycycline with filing, 5) vancomycin alone, 6)
      vancomycin with filing. The relevant canals were irrigated with 4ug/mL of either
      vancomycin or doxycycline antibiotic. Teeth were processed for scanning electron
      microscopy (SEM). Areas of biofilm remaining in the canals after antibiotic
      treatment were measured with Scion image analysis software using the SEM images.
      RESULTS: Vancomycin is more effective in reducing the overall biofilm area
      compared with doxycycline; moreover filing after antibiotic administration
      increased this effect. CONCLUSION: We can conclude that vancomycin had greater
      efficacy than doxycycline for inhibiting and reducing E. faecalis biofilms growth
      in root canals. However, it failed to completely eliminate biofilm formation.

PMID- 23130028
TI  - In Vitro Comparison of Dye Penetration through Four Temporary Restorative
      Materials.
AB  - INTRODUCTION: The purpose of this in vitro study was to compare the coronal seal
      of four temporary filling materials, Coltosol, Zonalin, Zamherir, and
      Intermediate Restorative Material (IRM) by the India ink dye penetration test.
      MATERIALS AND METHODS: Endodontic access preparations were prepared in 120
      extracted intact human premolars. The teeth were randomly divided into six groups
      including four experimental and two control groups. The access cavities in each
      group were sealed with Coltosol, Zonalin, Zamherir, and IRM; subsequently
      thermocycling was applied for 5-55C for 150 cycles. The teeth were immersed in
      10% India ink for 72 hours to assess leakage. The teeth were then rinsed, dried,
      and sectioned mesiodistally and evaluated under a stereomicroscope for dye
      penetration. Data were analyzed using one-way ANOVA and post hoc Tukey tests.
      RESULTS: Positive control specimens showed complete dye penetration, while
      negative controls had no penetration. In the experimental groups, the lowest and
      highest leakage scores were observed in the Zonalin and Coltosol groups,
      respectively (P<0.05). There were no statistically significant differences in
      marginal leakage between Zonalin-Zamherir and Coltosol-IRM groups. CONCLUSION:
      These results suggest that Zonalin and Zamherir have a superior seal and less
      micro-leakage into the canals compared to the two other materials.

PMID- 23130029
TI  - The effect of two post-space preparation techniques on the seal of resilon and
      gutta-percha obturation materials.
AB  - INTRODUCTION: The aim of this study was to compare the effect of post space
      preparation with Gates Glidden drills or hand files on the sealing ability of
      gutta-percha or Resilon obturation materials. MATERIALS AND METHODS: One-hundred
      and four single-rooted human teeth were instrumented and divided into four
      experimental groups (n=21 each) and two groups of positive and negative control
      (n=10). Forty-two roots of experimental groups were obturated with gutta-percha
      and Dorifill sealer; and 42 roots with Resilon/Epiphany self-etch using lateral
      compaction technique. Each gutta-percha or Resilon group was divided into two
      subgroups (n=21) and post-space prepared with either Gates Glidden drills or hand
      files and chloroform. After post space preparation, 5 mm of apical gutta-percha
      or Resilon was left intact. The whole system was sterilized with gamma-rays.
      Saliva leakage was tested using a split-chamber model. Specimens were monitored
      every 24 hours for 30 days. The data were analyzed using log-rank test and Cox
      regression analysis. RESULTS: There were no significant differences between the
      sealing ability of gutta-percha and Resilon. Furthermore, no significant
      difference was found between two different methods of post space preparation
      (P>0.05). CONCLUSION: Under the limitations of this ex vivo study, there were no
      significant differences between the sealing ability of Resilon and gutta-percha
      after post space preparation using Gates Glidden drills or hand files with the
      aid of chloroform.

PMID- 23130030
TI  - A comparative in vivo study of tissue reactions to four suturing materials.
AB  - INTRODUCTION: The purpose of this study was to compare the histopathologic
      reaction of four suturing materials: silk, polyvinylidene fluoride (PVDF),
      polyglycolic acid, and catgut in the oral mucosa of albino rabbits. MATERIALS AND
      METHODS: The twenty-one male mature albino rabbits which were used in this study
      were randomly divided into three groups of seven each. Silk, PVDF, polyglycolic
      acid and catgut suture materials were tested in the oral mucosa of these animals.
      The animals were sacrificed 2, 4, and 7 days after suturing. Two pathologists
      evaluated the samples by determining the presence and level of inflammation,
      granulation tissue, and fibrosis formation. Data were statistically analyzed by
      Kruskal Wallis and Mann-Whitney U tests. RESULTS: Histological features of the
      samples showed that PVDF and plain catgut suture materials produced more fibrous
      tissue (favorable response) on the fourth day in comparison with silk suture
      (P=0.02). Also, in the 7-day samples PVDF sutures produced the mildest
      inflammation when compared with the silk sutures (P=0.015). CONCLUSION: According
      to the results of this study, it can be convey that PVDF suture materials created
      mild tissue reactions and can be a reasonable candidate for suturing oral
      tissues.

PMID- 23130031
TI  - Periapical Status and Quality of Root canal Fillings and Coronal Restorations in
      Iranian Population.
AB  - INTRODUCTION: This cross-sectional survey determined the dental prevalence of
      apical periodontitis (AP) in selected Iranian population, and evaluated the
      influence of the quality of root canal treatment (RCT) and their coronal
      restorations (CR) on the periapical status. MATERIALS AND METHODS: A total of
      1064 panoramic radiographies were evaluated by two observers during 2009. The
      quality of RCT i.e. length/density of root fillings and CR in addition to
      periapical status of endodontically treated teeth were recorded. Their
      interrelationship was analyzed by Chi-squared, logistic regression and Spearman's
      rho statistics. Hosmer and Lemeshow tests were used for assessing fitness of
      logistic regression model and one sample k-s test was used for evaluating of
      normality of the data. RESULTS: Our results showed that 527 teeth (52%) of the
      endodontically treated teeth presented with AP radiographically. The percentages
      of teeth which fulfilled the criteria of an acceptable RCT or CR radiographically
      were 42.3 and 62.5 respectively. Incidence of AP among teeth with acceptable RCT
      (29.1%) was significantly lower than those suffering from unacceptable RCT
      (68.8%) (P<0.001). Moreover, adequate CR demonstrated a significantly better
      periapical status (58.6%) compared to teeth with inadequate CR (30.3%) (P<0.001).
      The incidence of AP ranged from 25.6% (good qualities) to 79.5% (bad qualities)
      (P<0.001). Cases with both unacceptable RCT/CR were 11 times more likely to have
      AP than cases with acceptable RCT/CR. The quality of RCT and CR were found to
      impact the periapical health of endodontically treated teeth. CONCLUSION: There
      are a significant high number of technically unacceptable endodontic and
      restorative treatments in Iran; therefore considerable efforts are needed to
      improve the standards of endodontic and restorative treatments.

PMID- 23130032
TI  - Coronal microleakage in root canals obturated with lateral compaction, warm
      vertical compaction and guttaflow system.
AB  - INTRODUCTION: Root canal obturation seals the root canal system to prevent re
      entry and/or growth of microorganisms. The provision of an appropriate
      restoration to coronally seal the access cavity affects the success of endodontic
      treatment. The purpose of this study was to evaluate the coronal microbial
      leakage in root canals that were either filled by lateral compaction, GuttaFlow
      or warm vertical compaction. MATERIALS AND METHODS: In this ex vivo study, 80
      single-rooted human extracted teeth were randomly divided into three experimental
      groups (n=20) and two positive and negative control groups (n=10). The teeth in
      experimental groups were obturated with cold lateral compaction, GuttaFlow system
      or warm vertical compaction techniques. After sterilization of the whole system
      with gamma-ray, saliva leakage was tested using a split-chamber model. Specimens
      were monitored every 24 hours for 30 days. The data were analyzed using log-rank
      and Kaplan-Meier survival analysis tests. RESULTS: There were no significant
      differences in impeding saliva leakage between the three experimental groups
      (P>0.05). CONCLUSION: Under the conditions of this ex vivo study, it can be
      concluded that the sealing ability of cold lateral compaction, warm vertical
      compaction and GuttaFlow system was comparable.

PMID- 23130033
TI  - A digital stereomicroscopic study of the furcation wall thickness of mesiobuccal
      roots of maxillary first and second molars.
AB  - INTRODUCTION: This study aimed to compare the thickness of the mesiobuccal furcal
      canal walls of first and second maxillary molars. MATERIALS AND METHODS: This
      study was performed on total of 30 first and second extracted molar teeth (15
      each). The mesiobuccal roots of each tooth were separated at the cement-enamel
      junction (CEJ) level and embedded in acrylic resin. The embedded roots were cut
      horizontally at two and four mm below the CEJ using a 0.20 mm blade (overall
      three sections CEJ, two and four mm below). Next, photographs of all the
      horizontal sections were taken using a digital stereomicroscope with identical
      magnifications (*20). Using the photographs, two independent observers measured
      and recorded the minimal thickness from the canal wall of the first mesiobuccal
      (MB1) and the second mesiobuccal (MB2) canals to the furcation area. Data
      analysis was performed by repeating the measurement Analysis of Variance. The
      analysis was completed by making paired comparisons using the Bonferroni alpha
      adjustment method. Statistical significance was set at P<0.05. RESULTS: In
      maxillary first molars, the mean (+/-SD) thickness of the canal furcal wall MB1
      in three sections were significantly higher than thickness of the canal furcal
      wall in MB2 (P<0.05). However there was no statistical difference between the
      mean (+/-SD) thickness of the canal furcal wall in the three sections (CEJ, 2 and
      4 mm below) of maxillary second molars MB1 and MB2 canals. CONCLUSION: Only the
      maxillary first molars demonstrated significantly lower furcal canal wall
      thickness (FCWT) values in the MB2 canals. Maxillary second molars MB canals did
      not demonstrate statistical difference in FCWT values.

PMID- 23130034
TI  - Biological apexogenesis of undeveloped tooth in a patient with spondyloepiphyseal
      dysplasia: a case report.
AB  - This case report describes treatment of a necrotic immature permanent mandibular
      first molar with pulpal necrosis in 9-year old female with spondyloepiphyseal
      dysplasia. The coronal half of the root canal was debrided with a file #30 to
      remove necrotic tissue, and irrigated with chlorhexidine 0.12%. Bleeding was
      evoked to form an intracanal blood clot; the wound was then dressed with calcium
      hydroxide medication and provisionally restored with GIC. This was repeated at
      intervals of 1, 3 and 6 months. After six months, radiographic evidence revealed
      thickening of dentinal walls and apical closure. The progressive increase in
      dentinal wall thickness and apical development suggests that desirable biologic
      responses can occur with this form of treatment for the necrotic open apex of
      immature permanent teeth.

PMID- 23130035
TI  - Comparison of Antimicrobial Efficacy of IKI and NaOCl Irrigants in Infected Root
      Canals: An In Vivo Study.
AB  - INTRODUCTION: Effective debridement of the root canal system with chemical
      irrigants prior to obturation is the key to long-term success of endodontic
      therapy. The purpose of this study is to compare the antibacterial activity of
      2.5% sodium hypochlorite (NaOCl) and 2% iodine potassium iodide (IKI) solutions
      as intracanal disinfectant in infected root canals during one-visit endodontic
      treatment procedure. MATERIALS AND METHODS: Thirty single-rooted teeth with
      necrotic pulps in 27 patients were selected according to specific
      inclusion/exclusion criteria and divided into two random groups. In group I,
      canals were irrigated with 2.5% NaOCl during instrumentation and in group II
      canals were initially irrigated with sterile saline during biomechanical
      preparation and then exposed to a 5-minute final irrigation with 2% IKI.
      Bacterial samples were taken before treatment (S(1)), and at the end of treatment
      (S(2)). Mann-Whitney U test was used for analysis. RESULTS: Bacteria were present
      in all initial samples. NaOCl was able to significantly reduce the number of
      colony forming units (CFU) from S(1) to S(2) in approximately 90% of canals. Only
      15% reductions in CFUs occurred after irrigation/instrumentation in group II;
      this degree of disinfection was not statistically significant. CONCLUSION:
      According to this study, although root canal irrigation with 2.5% NaOCl could not
      eradicate all bacteria within the canals; it was significantly superior in
      comparison with 2% IKI use.

PMID- 23130036
TI  - A comparative study between resilon and gutta-percha as a secondary root canal
      filling materials: an in vitro study.
AB  - INTRODUCTION: Adequate root canal seal following retreatment is essential for a
      successful outcome. Resilon/Epiphany (R/E) obturation system has been introduced
      as a substitute for conventional gutta-percha/sealer method. This in vitro study
      compared the amount of apical microleakage of R/E with gutta-percha/AH26
      (GP/AH26) sealer as secondary root canal filling following retreatment in human
      teeth. MATERIALS AND METHODS: Fifty human single-rooted lower premolar teeth were
      selected. After preparing them with ProTaper rotary NiTi instruments, all the
      canals were obturated using GP/AH26 sealer. After 10 days, all the samples were
      retreated using the same rotary NiTi instruments. The samples were divided
      randomly into two experimental groups A and B (n=20) and positive and negative
      control groups (n=5). In group A, all canals were obturated using GP/AH26 sealer
      and in group B all canals were obturated using R/E. After one week incubation in
      37C with 100% humidity, the amount of apical microleakage was evaluated with
      fluid filtration model. All the apical microleakage data were analyzed with Mann
      Whitney U test. RESULTS: The mean amounts of apical microleakage were 0.317 +/-
      0.287 and 0.307 +/- 0.281 uL/8min (fluid pressure=30 cm H2O) in experimental
      group A and B respectively; the difference was not statistically significant
      (P>0.05). CONCLUSION: R/E seems to be a good alternative for retreatment as a
      secondary root canal filling material. However, Resilon/Epiphany obturation
      system does not completely avert microleakage.

PMID- 23130037
TI  - The effect of three irrigants on the coronal leakage of the root canals system
      irrigants.
AB  - INTRODUCTION: The production of smear layer during canal instrumentation is
      thought to increase coronal microleakage even after canal obturation. Previous
      studies have shown that the type of irrigant does not necessarily affect the seal
      of the obturation. Our study aimed to evaluate the effect of three irrigation
      solutions (MTAD, citric acid and EDTA/NaOCl) on the coronal microleakage of root
      canals. MATERIALS AND METHODS: Fifty five intact single rooted teeth were
      instrumented and randomly divided into three experimental groups (15 teeth each)
      and two control groups (5 teeth each). Final irrigation was carried out with MTAD
      in group I, citric acid in group II, and EDTA/NaOCl in group III. EDTA/NaOCl was
      used for the negative control group and saline irrigation was carried out in the
      positive control group. After lateral compaction with gutta-percha, the access
      cavities of the experimental specimens were restored with temporary restorative
      material. Temporary cement was not used in the positive control group. In the
      negative control group, access cavities and foramen apices were sealed with glass
      ionomer. Microleakage of samples was measured using the dye penetration
      technique. Data were analyzed with ANOVA and Tukey test to determine statistical
      differences between groups. RESULTS: MTAD, citric acid and EDTA/NaOCl all had
      less microleakage compared to normal saline. However, no difference was detected
      between the experimental groups. CONCLUSION: In this study, all three groups
      demonstrated effective seal with gutta-percha obturation. This is likely to be
      due to various factors including their ability to remove smear layer.

PMID- 23130038
TI  - Multiple in vitro analyses of fracture resistance in maxillary central incisors
      restored with fiber posts.
AB  - INTRODUCTION: The resistance to fracture of endodontically treated teeth restored
      with esthetic post systems has not been extensively researched. This in vitro
      study compared the fracture patterns of endodontically treated teeth with
      esthetic post systems with different analysis methods. MATERIALS AND METHODS: A
      total of 26 recently extracted human maxillary central incisors were decoronated
      and then endodontically treated. Teeth were restored with quartz fiber posts. All
      posts were cemented with Panavia dual curing adhesive resin cement and
      subsequently restored with composite cores. Three methods were used to test
      fracture resistance. Each specimen was embedded in acrylic resin and then secured
      in a universal load-testing machine. A compressive load was applied at 135o
      degree angle at a crosshead speed of 1 mm/min to the long axis of the tooth until
      fracture occurred. The two other methods, finite element analysis (FEA) and photo
      elastic study used the same angulation and 90 N force to simulate the first
      method. The data were then compared. RESULTS: Clinical results indicated that
      fracture was most likely to occur between core and dentin, and then in the
      cervical 1/3 of the root. Photo elastic study demonstrated similar results; the
      highest stresses occurred at the junction of dentin and core contralateral to the
      side where force was applied. FEA also confirmed these results; however it also
      showed that the highest stresses arise at the dentin/core junction contralateral
      to the force point. CONCLUSION: All three techniques reiterate that the risk of
      fracture is greatest at the cervical dentin/core junction.

PMID- 23130039
TI  - Endodontic management of a fused mandibular second molar and paramolar: a case
      report.
AB  - Tooth fusion is a developmental anomaly characterized by the union between the
      dentin and/or enamel of at least two separately developing teeth. The fusion of
      posterior teeth is an uncommon occurrence. In this article, we report a rare case
      of unilateral fusion of a mandibular second molar with a paramolar. Carious
      exposure mandated endodontic treatment. The unusual morphology and complex root
      canal system makes diagnosis and treatment difficult. In this case, successful
      endodontic management was carried out with precise application of hand and rotary
      techniques.

PMID- 23130040
TI  - Nonsurgical endodontic treatment of a maxillary central incisor with two separate
      roots: a case report.
AB  - The success of endodontic therapy requires knowledge of the internal and external
      dental anatomy and its variations in presentation. This case report involves
      endodontic treatment of a traumatized maxillary central incisor with two separate
      roots.

PMID- 23130041
TI  - Retreatment of a 6-canalled mandibular first molar with four mesial canals: a
      case report.
AB  - Successful root canal treatment requires adequate knowledge regarding morphologic
      variations in root canal system of teeth. This report describes a six-canalled
      mandibular first molar with four mesial root canals requiring endodontic
      retreatment. The two additional canals in the mesial root were found during
      retreatment with the aid of illumination and magnification. In conclusion, the
      possibility of atypical morphology and additional canals should never be
      overlooked.

PMID- 23130043
TI  - Presence of leptin in chronic periapical lesions.
AB  - INTRODUCTION: Studies have shown the regulatory role of Leptin in bone formation,
      its expression in adipose tissue as well as increased levels in circulation
      following the adminstration of inflammatory stimuli such as lipopolysaccharides
      (LPS). However, there is little data evaluating the role of Leptin in
      inflammatory periapical lesions. The aim of this study was to evaluate the
      presence and concentration of Leptin in chronic periapical lesions. MATERIALS AND
      METHODS: Chronic periapical lesions with different sizes were collected during
      periapical surgery of the mandibular molars from twenty patients and cultured for
      72 hours. The ELISA method determined the concentration of Leptin in supernatant
      fluids of explants cultures. Statistical analysis was performed using non
      parametric tests (Mann-Whitney U, Chi-Square and Spearman's Correlation
      Coefficient). RESULTS: Leptin was found in all samples with the average
      concentration of 405.55+/-102.98 (pg/mL). There was no significant correlation
      between the concentration of Leptin and BMI, and the diameters of lesions.
      CONCLUSION: Leptin can be considered an inflammatory mediator and is likely to
      have a role during the early phases of dental periapical lesions.

PMID- 23130042
TI  - A review of novel bacterial complex lipids: implications for the pathogenesis of
      apical periodontitis.
AB  - The importance of the role played by bacteria in the pathogenesis of pulpal and
      apical disease has been established. One of the characteristics of apical
      periodontitis is apical bone resorption, which is due to apical immune response
      to bacterial infection. Recently, novel bacterial complex lipid called
      phosphorylated dihydroceramides has been discovered to be of inflammatory
      activators. The bacterial lipids stimulate prostaglandin E2, IL-6, and TNF-alpha
      secretion, inhibit osteoblast differentiation and function, and induce osteoclast
      formation. The biological activities are in Toll-like receptor 2 (TLR2)-dependent
      manner. These new findings imply that bacterial lipids could be important
      virulent factors that cause apical bone resorption. Future investigations may
      determine the significance of the bacterial lipids in the pathogenesis and
      treatment of endodontic diseases.

PMID- 23130044
TI  - Sealing Ability of MTA and CEM Cement as Root-End Fillings of Human Teeth in Dry,
      Saliva or Blood-Contaminated Conditions.
AB  - INTRODUCTION: Sealing ability is an important factor for a root-end filling
      material in endodontic surgeries. This in vitro study aimed to compare the
      sealing ability of mineral trioxide aggregate (MTA) and a new endodontic cement
      named calcium enriched mixture (CEM) cement as root-end filling materials.
      MATERIALS AND METHODS: The experiments were carried out in dry, saliva or blood
      contaminated root-end cavities of hundred single-rooted extracted human teeth.
      After decoronation, the root canals were cleaned, shaped, obturated, and stored
      in 100% humidity for 5 days. Removing the apical 2-3mm of each root, a 3mm deep
      root-end cavity was ultrasonically prepared. Samples were randomly divided into 2
      test groups of 45 roots/experimental material, and one subgroup (n=15) for each
      environmental condition as follows; a) dried before placing the filling material,
      b) filled after contamination with saliva, and c) filled after contamination with
      blood. Ten roots were used as positive/negative controls. Samples were placed in
      an incubator at 37 degrees C for a day and immersed in methylene blue dye under
      reduced pressure environment for 48hours. Roots were sectioned longitudinally and
      examined under stereomicroscope by an independent observer. RESULTS: Using
      Kruskal-Wallis and Mann-Whitney U tests with Bonferroni correction, the results
      demonstrated significantly less leakage for the CEM cement in saliva contaminated
      condition when compared to MTA (P<0.001). CONCLUSION: It can be concluded that
      the sealing ability of CEM cement was superior to MTA in saliva contaminated
      condition.

PMID- 23130045
TI  - Clinical and Radiographic Success of Pulpotomy with MTA in Primary Molars: 30
      Months Follow up.
AB  - INTRODUCTION: Pulpotomy of carious primary teeth with an exposed pulp is a common
      treatment option. Pulpotomy has been conducted with various medicaments over the
      years. The aim of this study was to evaluate clinical and radiographic success of
      primary vital pulpotomy with ProRoot and Root MTA. MATERIALS AND METHODS: In this
      randomized clinical trial, children aged between 3-7 years who met the inclusion
      criteria were enrolled. A total of 70 teeth were deemed suitable under the
      inclusion criteria and teeth were randomly divided into the 2 groups; ProRoot and
      Root MTA. Pulpotomy was performed and immediately followed by coronal amalgam
      restoration. The clinical and radiographic follow ups were conducted 6, 12, 18,
      30 months post-operatively. The data were analyzed using Exact Fisher test.
      RESULTS: At the final follow up, 28 teeth in ProRoot MTA and 26 teeth in Root MTA
      were evaluated. In the Root MTA group, 1 tooth had exfoliated and one had an
      abscess and furcal radiolucency radiographically. In ProRoot MTA group, external
      resorption was observed in 1 tooth. Statistical analysis did not show significant
      difference in success rate between 2 groups after 30 months. CONCLUSION: The
      success rates of Root and ProRoot MTA are similar, indicating that pulpotomy can
      be carried out successfully in both primary molars.

PMID- 23130046
TI  - Efficacy of Three Different Methods in the Retreatment of Root Canals Filled with
      Resilon/Epiphany SE.
AB  - INTRODUCTION: The purpose of this study was to evaluate the efficacy of three
      methods in removal of Resilon/new Epiphany self-etch (SE) soft resin endodontic
      obturation system. MATERIALS AND METHODS: Thirty extracted single rooted human
      teeth were prepared for endodontic treatment and obturated with Resilon/Epiphany
      SE. The roots were randomly divided into three groups; group 1 roots were
      retreated using Mtwo R/Mtwo files; group 2 were retreated using Mtwo R/Mtwo
      accompanied with chloroform; and group 3 were retreated using Mtwo R/Mtwo
      accompanied with Endosolv R. The cleanliness of canal walls was determined using
      scanning electron microscopy. Data were analyzed using ANOVA and LSD tests.
      RESULTS: Endosolv R combined with rotary files was more efficient in material
      removal compared to chloroform combined with rotary files and rotary files alone
      (P<0.05). Also, chloroform combined with rotary file was more efficient than
      rotary file alone in removing filling material from the root canals. Significant
      difference was found within group 1 between the coronal third compared to the
      middle and apical thirds (P<0.05). In group 2, there were more material remnants
      in the apical third (P<0.05). In group 3, there was no significant difference
      between the three segments of the root canals (P>0.05). CONCLUSION: All
      techniques left filling material remnants and debris on the root canal walls.
      Endosolv R combined with rotary files most effectively removed filling materials
      from the root canals, especially in the apical third.

PMID- 23130047
TI  - Microscopic evaluation of cleaning efficiency of three different nickel-titanium
      rotary instruments.
AB  - INTRODUCTION: This study compared the cleaning efficiency of Mtwo, Race and Medin
      Nickel-Titanium (NiTi) rotary instruments. MATERIALS AND METHODS: Sixty
      mandibular molar mesial roots were selected with angle curvatures between 25-35
      degrees and divided into three groups; each containing 20 teeth. Canals were
      prepared with the rotary files and irrigated with 2.5% NaOCl solution after each
      instrument. Total of 5mL of normal saline was used as the final rinse;
      subsequently the canals were dried with paper points. The amount of debris and
      smear layer in three parts of the root canal walls was evaluated using SEM and
      the data were analyzed by using the Kruskal-Wallis test and the Mann-Whitney U
      test. RESULTS: The results for remnant debris in the coronal part of root canals
      were similar, whereas in the middle third, Mtwo instruments achieved
      significantly better results compared to Race and Medin instruments. In the
      apical third of the root canals more debris was created by Race instruments.
      CONCLUSION: Overall, Mtwo instruments had greater success in producing clean
      canals.

PMID- 23130048
TI  - The Effect of Calcium Hydroxide on the Short and Long-Term Sealing Properties of
      MTA Apical Barrier.
AB  - INTRODUCTION: The aim of this study was to evaluate the effects of remnant root
      canal medicament, calcium hydroxide on the short and long term sealing ability of
      mineral trioxide aggregate (MTA) apical barrier. MATERIALS AND METHODS: Fifty
      single-rooted teeth were prepared and apical resorptions were made using sulfuric
      acid. The teeth were allocated into two experimental groups and two control
      groups. In group 1, calcium hydroxide was placed into canals for one week. In
      group 2, no medication was placed. In both groups, a 4-mm MTA plug was placed in
      the root canals. The remaining portion of the canal was filled with gutta
      percha/sealer. The microleakage was evaluated after 7 days and 3 months using
      fluid filtration technique. Repeated measurement ANOVA was used for statistical
      analysis. RESULTS: There was no significant difference in sealing ability between
      the two groups in either time periods. In both groups, microleakage decreased
      after three months but this decrease was not statistically significant.
      CONCLUSION: Medication with calcium hydroxide had no adverse effect on the short
      and long-term sealing properties of MTA plug.

PMID- 23130049
TI  - Comparison of three pulpotomy agents in primary molars: a randomised clinical
      trial.
AB  - INTRODUCTION: Pulpotomy is an accepted treatment for the management of cariously
      exposed pulps in symptom free primary molars. The purpose of this study was to
      compare the clinical and radiological outcomes of three different single-visit
      vital pulp therapies including pulpotomy with electrosurgery (ES), formocresol
      (FC) and ferric sulfate (FS) in cariously exposed primary molar teeth. MATERIALS
      AND METHODS: Seventy-six patients, 5-10 years old, were enrolled in this clinical
      investigation. One primary molar tooth of each patient was selected for this
      study. Samples were randomly divided into three groups. Teeth were treated with
      FC in group 1 (i.e. control group) (n=24), FS in group 2 (n=28), and ES in group
      3 (n=24) using standardized pulpotomy procedures. All treated teeth were
      clinically and radiographically evaluated after 6 and 9 months. Statistical
      analysis was performed using Fishers exact test. RESULTS: The overall success
      rate in groups 1, 2 and 3 was 87.5%, 82.1% and 83.3%, respectively. Favorable
      clinical and radiological success rates of FS and ES pulpotomy was observed which
      was comparable to FC. CONCLUSION: FS and ES can be considered alternative
      materials for the pulpotomy of primary molars.

PMID- 23130050
TI  - A Comparative Study of MTA Solubility in Various Media.
AB  - INTRODUCTION: Solubility of root filling materials is heavily influenced by the
      environment they are in contact with. This study compared the solubility of
      ProRoot MTA in deionized water and synthetic tissue fluid. MATERIALS AND METHODS:
      Forty specimens of prepared MTA were immersed in deionized water and synthetic
      tissue fluid (20 samples each). The solubility was assessed after 7 and 28 days.
      Scanning electron microscope observation was also performed. The mean weight loss
      was evaluated using a digital scale. Data were analyzed using one-way ANOVA.
      Tukey test was performed for multiple comparisons. RESULTS: MTA solubility in
      synthetic tissue fluid was significantly lower than deionized water after 7 and
      28 days (P<0.05). Secondary electron detectors revealed the presence of lumps and
      platelets on the surfaces of both specimens. Also, more voids were observed in
      specimen stored in deionized water. CONCLUSION: MTA dissolved faster in deionized
      water than synthetic tissue fluid. Despite this, the solubility of this material
      in both media was acceptable.

PMID- 23130051
TI  - Radiographic evaluation of maxillary anterior teeth canal curvatures in an
      Iranian population.
AB  - INTRODUCTION: Complete knowledge of root canal curvature is a critical factor in
      successful endodontic treatment. The aim of this study was to investigate the
      direction, radius and degree of curvature of maxillary anterior teeth and the
      relationship between the radius and degree of curvature in Babol, a northern city
      of Iran. MATERIALS AND METHODS: A total of 242 radiographs of maxillary anterior
      teeth (central, lateral and canine) were taken by periapical parallel technique
      and processed by automatic processing. The degree of canal curvature was measured
      only at mesiodistal direction with Schneider method and classified according to
      Seidberg method. Statistical analysis was performed with Kruskal Wallis and Mann
      Whitney U tests. RESULTS: Overall, 153 (62%) teeth had curvatures; 35.3% were
      mesially inclined and 64.7% were distally inclined. The degree of canal curvature
      was categorized into small, intermediate, and severe, that is 39.3%, 44.6% and
      16.1%, respectively. The mean value of root curvature angle was 7.24 degrees +/
      9.03 degrees  in central incisors, 12.08 degrees +/-11.02 degrees  in lateral
      incisors, and 15.08 degrees +/-12.02 degrees  in canines respectively. There was
      significant correlation between type of tooth and degree of curvature (P=0.000).
      Significant correlation was not found between the type of tooth and radius of
      curvature (P=0.365). CONCLUSION: In the present study, 62% of maxillary anterior
      teeth had some form of curvatures; highest degrees of curvature were attributed
      to the canine teeth.

PMID- 23130052
TI  - An In Vitro Comparative Study on the Antimicrobial Effects of Bioglass 45S5 vs.
      Calcium Hydroxide on Enterococcus Faecalis.
AB  - INTRODUCTION: An ideal intracanal medicament should be able to eliminate any
      remaining intracanal microorganism. The aim of this study was to compare the
      antimicrobial effects of Bioglass 45S5 with calcium hydroxide on Enterococcus (E)
      faecalis in-vitro. MATERIALS AND METHODS: Direct exposure test (DET) was used to
      evaluate the antimicrobial effect of Bioglass 45S5, calcium hydroxide and normal
      saline (control group) on 80 paper cones contaminated with E. faecalis
      suspension. All samples were aseptically transferred into BHI culture medium to
      quantify microbial concentration in periods of 1, 24, 48 and 72 hours. Turbidity
      of the culture medium was measured via optical density (OPD) method with a
      spectrophotometer (wavelength=540nm). Results were then analysed statistically
      using student t-test. RESULTS: Mean difference of optical density between
      Bioglass 45S5 and calcium hydroxide appeared insignificant within 1 hour of the
      test period (P>0.05); however calcium hydroxide showed significantly greater
      antimicrobial properties after 24 hours (P<0.05). Antimicrobial effect of both
      materials displayed significant increases with time. CONCLUSION: Although both
      Bioglass 45S5 and calcium hydroxide exhibited antimicrobial effects against E.
      faecalis, neither attained complete eradication of bacteria. However, calcium
      hydroxide seemed to have superior disinfecting effect.

PMID- 23130053
TI  - Management of a hopeless mandibular molar: a case report.
AB  - Intentional tooth reimplantation can be an alternative treatment option for teeth
      with poor or hopeless prognosis where coronal and surgical endodontic
      treatment(s) are not possible. This technique may help to restore a natural tooth
      to function in preference to prosthesis/implant replacements. A 38-years old male
      was referred to private practice with persistent chronic apical periodontitis of
      a previously root canal treated mandibular left first molar. A furcal perforation
      and distolingual cusp fracture was previously repaired and treated with amalgam
      (~5 years ago). In view of the patient/tooth's limitations, intentional
      reimplantation was planned using CEM cement retrograde filling. Clinical and
      radiographic follow-up during 2 years postoperatively revealed no sign/symptoms
      of infection or inflammation. Moreover, periradicular healing was evident on
      radiographs.

PMID- 23130054
TI  - Antibiotic prescription for endodontic treatment: general dentist knowledge +
      practice in shiraz.
AB  - INTRODUCTION: Diseases of the dental pulp and periapical tissues are chiefly
      caused by microorganisms. Antibiotics are used in some endodontic cases; however,
      successful cases can predominantly be achieved by mechanical and chemical
      cleaning of the canal or surgical intervention. MATERIALS AND METHODS: The aim of
      this study was to determine the knowledge of General Dental Practitioners (GDPs)
      in Shiraz in respect to antibiotic prescriptions during and after endodontic
      treatment. A one-page questionnaire was sent to 200 active general dentists. Of
      the 120 surveys returned, 93 were accepted. The data were analyzed using t-test,
      Chi-square, ANOVA and Fisher's Exact Test. RESULTS: Only 29% of dentists had full
      knowledge (correct answers to all questions) of antibiotic prescription protocols
      in pulpal and periapical disease. Amoxicillin 500 mg capsule was the drug of
      choice of dentists. Total of 42% of GDPs had full knowledge of antibiotic
      prescription protocols for persistent or systemic infections cases. GDPs more
      recently qualified had slightly greater knowledge compared to GDPs with
      experience; however, this difference was not significant. Also, there was no
      significant difference between genders. CONCLUSION: General practitioners'
      knowledge about antibiotics seems inadequate and further education is recommended
      to update the practitioners.

PMID- 23130055
TI  - Comparison Between the Accuracy of NovApex Apex Locator and Radiographs in
      Determining Radiographic Apex.
AB  - INTRODUCTION: Determination of the canal working length with radiographs has many
      drawbacks. Electronic apex locators have been developed to overcome some of these
      problems. Recently, a newly designed apex locator called NovApex has been
      introduced. All the studies conducted to determine the accuracy of NovApex have
      been carried out in-vitro on extracted teeth. The aim of this in vivo study was
      to evaluate the accuracy of NovApex compared with traditional radiographic
      method. MATERIALS AND METHODS: Twenty-five patients whose lower molars that were
      candidates for extraction were selected. The teeth were accessed, and the
      radiographic working length was determined by measuring the length of the initial
      file 0.5mm short of the radiographic apex. Then, NovApex apex locator was used to
      measure the electronic working length. Subsequently, the tooth was extracted, and
      the actual working length was measured by introducing a size #15 K-file into each
      canal until the file tip was visible at the apex, then 1.5mm was subtracted to
      attain the working length. Cohen's Kappa was computed for each of the methods
      versus actual working length as a measure of reliability. The accuracies were
      compared using Chi-square test. RESULTS: The accuracy of NovApex apex locator and
      radiographic method in detecting the apical end point within +/-0.5mm was 74.7%
      and 68%, respectively; this was not significantly different (P<0.001).
      CONCLUSION: The NovApex apex locator is useful in detecting the apical end point
      with the accuracy similar to radiographic method. However, neither technique is
      fully reliable in detecting the apical end point of the canal.

PMID- 23130056
TI  - Efficacy of two rotary systems in removing gutta-percha and sealer from the root
      canal walls.
AB  - INTRODUCTION: The aim of this in vitro study was to compare the efficacy of two
      retreatment rotary systems in removal of gutta-percha (GP) and sealer from the
      root canal walls with and without use of solvent. MATERIALS AND METHODS: Sixty
      single-canalled distal roots of mandibular molars were prepared and root filled
      with gutta-percha and AH26. Each canal was randomly allocated to receive one of
      the retreatment techniques, Mtwo R or ProTaper. The groups were further divided
      into two subgroups: with or without the use of solvent. The cleanliness of canal
      walls was determined by stereomicroscope and scanning electron microscopy.
      RESULTS: The results showed that Mtwo R without the use of solvent was more
      efficient in material removal compared to ProTaper D (P<0.05). Most remnants were
      found in the apical third of the canals (P<0.05). CONCLUSION: Mtwo R seems to be
      an efficient rotary system for endodontic retreatment of root canal with GP.

PMID- 23130057
TI  - Cyclic Fatigue Resistance and Fractographic Analysis of Race and Protaper Rotary
      NiTi Instruments.
AB  - INTRODUCTION: This study investigated the fatigue and fracture modes of RaCe and
      ProTaper rotary instruments. MATERIALS AND METHODS: Fatigue resistance was
      evaluated by rotating the files 30 degrees  or 60 degrees  and with 2 or 5mm
      radius of curvature. RaCe taper 06 size 25 and ProTaper F1 files (n=40) were
      used. The number of rotations to failure was analyzed by two-way ANOVA and
      independent sample t-test. Fracture surfaces were examined under a scanning
      electron microscope. RESULTS: Both files exhibited significantly more resistance
      to fracture when angle severity was reduced and increase in curvature radius
      (P=0.000). ProTaper demonstrated higher number of cycle of failure (P=0.0029) in
      one group (r=5mm, 60o). SEM observation revealed fatigue mark/features in 17
      specimens, shear characteristics in 37 samples, and tensile overload in 26
      samples. CONCLUSION: Radius of curvature was the main factor in torsional and
      fatigue failures.

PMID- 23130058
TI  - Sealing ability promoted by three different endodontic sealers.
AB  - INTRODUCTION: The aim of this study was to evaluate the apical and coronal seal
      of endodontic filling promoted by the combined use of Sealer 26/gutta-percha,
      Endofill/gutta-percha and Resilon/ Epiphany. MATERIALS AND METHODS: A total of 38
      extracted human canine teeth were selected; 10 teeth for each test group and 4
      for each control group. After conducting conventional endodontic treatment, the
      teeth were immersed in saline solution for thirty days, and subsequently sealed
      and stored in India ink for seven days. They were then cleaned and evaluated for
      infiltration by stereoscopic microscope. The data were statistically analyzed by
      ANOVA and Bonferroni tests. RESULTS: The results showed no significant
      differences between the three groups of filling materials used. CONCLUSION:
      Within the limitations of this in vitro study, no material showed superiority in
      their apical and coronal seal.

PMID- 23130059
TI  - MTA Apical Plug and Clinical Application of Anatomic Post and Core for Coronal
      Restoration: A Case Report.
AB  - Apexification with calcium hydroxide is associated with certain difficulties,
      such as longer treatment time, risk of tooth fracture and incomplete
      calcification of apical bridge. Mineral trioxide aggregate (MTA) is an
      alternative material that can be used for apexification of open apices due to its
      biocompatibility, non-mutagenicity, non-neurotoxicity, regenerative abilities,
      and good sealing properties. This case report demonstrates application of MTA
      apical plug and anatomic post and core for the reconstruction of maxillary
      central incisor. The patient was recalled after six months and no complications
      were noted. Periapical radiographs demonstrated good adaptation of anatomical
      post and core to post space and the complete healing of the periapical lesion.
      This new technique is particularly advantageous in teeth which have open apex,
      root canals that are not round, wide canals and thin radicular dentin. It is also
      useful for who request in patients fewer visits.

PMID- 23130060
TI  - One-visit RCT of Maxillary Incisors with Extensive Inflammatory Root Resorption
      and Periradicular Lesions: A Case Report.
AB  - Inflammatory external root resorption (IERR) is a pathological phenomenon of
      microbial origin. This study reports a case of external apical inflammatory root
      resorption of maxillary incisors associated with periradicular lesions in a 22
      year old female, which was successfully treated by one-visit root canal therapy
      (RCT). Radiographic investigation revealed periapical radiolucencies in the upper
      incisors associated with varying degrees of external inflammatory root resorption
      of teeth 12, 21 and 22. One-visit RCT of all involved teeth was carried out.
      Access cavities were permanently restored after 1 week. Clinical and radiographic
      examinations at 1 day, 1 week and 14 month follow-up demonstrated complete
      resolution of patient's signs/symptoms. The incisors were fully functional, and
      complete bone healing of the apical radiolucencies had taken place. The treatment
      outcomes demonstrated that IERR associated with periradicular lesions can respond
      successfully to one-visit RCT when conducted with adequate disinfection and a
      satisfactory coronal seal. Hence, one-visit RCT may be a good alternative to
      multiple-visit RCT involving intra-canal medicaments.

PMID- 23130061
TI  - Conventional versus digital radiographs in detecting artificial voids in root
      canal filling material.
AB  - INTRODUCTION: Inappropriate condensation of gutta-percha or improper use of
      sealer can lead to voids in root canal filling material and consequent failure of
      the treatment. Timely detection of voids within root canal filling may prevent
      complications. In this study, we compared the accuracy of digital and
      conventional radiograph for detecting voids within root canal fillings. MATERIALS
      AND METHODS: The root canals of 50 extracted maxillary permanent incisors were
      prepared and filled with gutta-percha and sealer. The teeth were then randomly
      divided into two groups of 25 incisors. The teeth were imaged using the
      paralleling technique with E-speed film and digital/digital zoomed system. The
      accuracy of radiographic techniques was evaluated for detecting voids by three
      independent observers. Presence/absence of voids was recorded and compared with
      the baseline data. The sensitivity, specificity, accuracy and positive and
      negative predictive values was recorded. RESULTS: The sensitivity, specificity
      and accuracy of conventional radiography and digital radiography were 48%, 52%,
      50%, and 82.7%, 80% and 81.3%, respectively. The positive and negative predictive
      value of conventional radiography was 50%. Digital images showed the positive
      predictive value of 80.3% and negative predictive value of 83.5%. The values of
      positive and negative predictive were reported as 81.6% and 81.1% in digital
      zoomed images. CONCLUSION: Digital and digital zoomed images performed better
      than conventional radiographs in detecting voids, but there were no differences
      between the performances of both digital images.

PMID- 23130062
TI  - Antibacterial effect of calcium hydroxide on intraluminal and intratubular
      enterococcus faecalis.
AB  - INTRODUCTION: Root canal treatment involves the elimination of intraradicular
      microorganisms. Calcium hydroxide [Ca(OH)(2)] is the most widely used canal
      dressing material. Enterococcus faecalis (E. faecalis) has been reported to be
      resistant to Ca(OH)(2) in-vivo. The purpose of this study was to evaluate the
      efficacy of Ca(OH)(2) on the elimination of intraluminal and intratubular E.
      faecalis. MATERIALS AND METHODS: Thirty six human single-rooted teeth were
      contaminated with E. faecalis. Thirty specimens in the experimental group were
      treated with 10% Ca(OH)(2); six specimens were treated with normal saline as the
      positive control (n=6). Specimens from experimental group were randomly divided
      into two subgroups of 15 each. In subgroup A, specimens were incubated and
      sampled after one day and in subgroup B, they were tested at day seven. Paper
      points and Gates Glidden burs were used to obtain the intraluminal and
      intratubular E. faecalis respectively. Samples obtained from these root canal
      preparations were analyzed for bacterial load by counting the number of colony
      forming units (CFUs). Mann-Whitney and t-test were used for analysis. RESULTS:
      Group B had significant decrease in CFUs compared with group A with both sampling
      methods (P<0.001). No differences were observed between the antimicrobial
      properties of Ca(OH)(2) against intraluminal and intratubular E. faecalis. After
      1 week, there was a significant reduction in CFU load with Ca(OH)(2) intra canal
      medication. CONCLUSION: Ca(OH)(2) showed the same antimicrobial efficacy on
      intraluminal and intratubular E. faecalis.

PMID- 23130063
TI  - Success rate of nonsurgical endodontic treatment of nonvital teeth with variable
      periradicular lesions.
AB  - INTRODUCTION: Bacterial infection of tooth pulp can progress into periapical
      diseases. Root canal treatment has been established as the best treatment. In
      cases of failure, nonsurgical retreatment of teeth is preferred to surgical
      procedure and extraction. MATERIALS AND METHODS: In this historical cohort study,
      104 permanent teeth with apical lesion were treated during 2002-2008. All teeth
      showed radiographic evidence of periapical lesion varying in size from 1 to
      >10mm. A total of 55 teeth were treated with initial root canal treatment and 49
      teeth required retreatment. Patients were recalled up to ~7 years. All
      radiographs were taken by RSV MAC digital imaging set and long cone technique.
      The presence/absence of signs and symptoms and periapical index scores (PAI) were
      used for measuring outcome. Teeth were classified as healed
      (clinical/radiographic absence of signs and symptoms) or diseased
      (clinical/radiographic presence of signs and symptoms). The data were
      statistically analyzed using student t-test and Pearson chi-square or fisher's
      exact test. RESULTS: The rate of complete healing for teeth with initial
      treatment was 89.7%, and for retreatment group was 85.7%; there was no
      significant difference. Size of lesions did not significantly affect the
      treatment outcomes. Success of tooth treatment did not reveal significant
      correlation with gender and number of roots. CONCLUSION: Orthograde endodontic
      treatment/retreatment demonstrates favorable outcomes. Thus, nonsurgical
      endodontic treatment/retreatment should be considered as the first choice in
      teeth with large periapical lesion.

PMID- 23130064
TI  - Fracture strength of mesiobuccal roots following canal preparation with hand and
      rotary instrumentation: an in vitro study.
AB  - INTRODUCTION: The aim of this in vitro study was to compare the effect of hand
      and rotary instruments on fracture strength of tooth roots. MATERIALS AND
      METHODS: Thirty two teeth were randomly divided into two experimental groups of
      15 each and one negative control group with two samples. In group 1, step-back
      technique with conventional stainless steel K-files was used, and in group 2,
      instrumentation was performed using rotary Ni-Ti Hero642. Samples in control
      group did not receive cleaning or shaping after access cavity preparation. After
      obturating each canal, tip of the spreader was locked within canal. The required
      force for root fracture was measured using Instron testing machine. Recorded data
      was statistically analyzed using t-test. RESULTS: The mean and standard deviation
      force required for vertical root fracture were 50.33+/-19.1 and 63.1+/-25.46 N
      for hand and rotary groups respectively. However, no significant difference was
      found between experimental groups. CONCLUSION: The results indicate that the
      manual technique did not lower fracture strength of obturated roots in comparison
      with the rotary preparation technique.

PMID- 23130065
TI  - Clinical management of dens invaginatus type 3: a case report.
AB  - Dens invagination (DI) is a developmental abnormality of teeth which frequently
      results in a complex internal anatomy of the root canal system. DI type 3 is an
      anomaly characterized by infolding of enamel and dentin extending into the root
      apex. This may present difficulties when forming a diagnosis and treatment plan.
      Many treatment modalities have been presented in case reports for DI type 3, but
      there is insufficient evidence to recommend a therapy. This case report presents
      the successful nonsurgical root canal treatment of a maxillary canine with an
      open apex DI type 3, necrotic pulp, and an associated large periradicular lesion.

PMID- 23130066
TI  - Endodontic treatment of a hypertaurodont mandibular second molar: a case report.
AB  - A 28-year old patient was referred for endodontic treatment of his left
      mandibular second molar. The patient had no history of systemic diseases and his
      chief complaint was spontaneous pain in left posterior region of mandible.
      Clinically, there was a deep caries in the left mandibular second molar.
      Radiographic examination of this tooth revealed a long crown containing large
      pulp chamber and two short roots with a apically located furcation, indicating
      hypertaurodontism. After coronal access preparation, five orifices were found
      including mesiolingual, mesiobuccal, distobuccal, mid-distal and distolingual.
      Subsequent to root canal preparation, a modified filling technique was used for
      canal obturation. After one year the treated tooth was symptom free.

PMID- 23130067
TI  - Effect of Hydroxyapatite and Bovine Serum Albumin on the Antibacterial Activity
      of MTA.
AB  - INTRODUCTION: The purpose of this study was to compare the inhibitory effect of
      bovine serum albumin (BSA) and hydroxyapatite (HA) on the antibacterial activity
      of white-colored MTA (WMTA) against Staphylococcus (S.) aureus and Streptococcus
      (S.) mutans after 24 and 72 hours. MATERIALS AND METHODS: All materials were
      prepared according to the manufacturer's directions immediately before testing.
      The antibacterial effect of each group (WMTA, WMTA+BSA and WMTA+HA) was
      determined by measuring the diameter of zone of inhibition in millimeters after
      incubation at 37 degrees C for 24 and 72 hours in a humid atmosphere. Each test
      was repeated three times. Data were analyzed using ANOVA and Tukey's test.
      RESULTS: In the 24 hours samples as well as in 72 hours samples, the
      antibacterial activity of MTA+HA group was significantly greater than two other
      groups against S. aureus (P<0.05). However, the antibacterial activity of MTA+HA
      group against S. mutans was not significantly different from the MTA group in 24
      hours as well as 72 hours samples. BSA reduced the antibacterial activity of MTA
      against both tested bacteria in the 24 and 72 hour samples (P<0.05). CONCLUSION:
      The products studied exhibited antibacterial activity. However, in both time
      intervals, the MTA+HA group exerted the greatest activity against S. mutans and
      S. aureus.

PMID- 23130068
TI  - Comparing microleakage in root canals obturated with nanosilver coated gutta
      percha to standard gutta-percha by two different methods.
AB  - INTRODUCTION: Favorable apical seal of root filling materials is a crucial factor
      for a successful root canal treatment. The aim of this in vitro study was to
      compare bacterial and dye microleakage of two root canal filling materials
      including standard gutta-percha and nanosilver coated gutta-percha, and to
      evaluate the agreement between results of these two methods. MATERIALS AND
      METHODS: Fifty-eight extracted single-rooted teeth were randomly divided into two
      experimental groups of 26 each, and two control groups of three each. After
      decoronation, root canals were instrumented by crown-down technique. Obturation
      was conducted using standard gutta-percha in one of experimental groups and
      nanosilver-coated gutta-percha in another group. AH26 sealer was used as the
      sealer in both experimental groups. Bacterial leakage was investigated after 60
      days using Enterococcus (E.) faecalis microbial strains, and dye leakage was
      assessed during 72 hours using 1% methylene blue. The data were statistically
      analyzed by Chi-square test, Kaplan-Meier survival analysis, and Cohen's Kappa.
      RESULTS: There was 84% bacterial leakage in standard gutta-percha group and 76%
      in nanosilver gutta-percha group. Complete dye leakage occurred in 24% and 27% of
      standard and nanosilver gutta-percha groups, respectively. The above difference
      between groups was not significant. In the samples with leakage, recorded times
      of leakage were not significantly different. There was no significant measure of
      agreement between dye and bacterial penetration along root-end fillings.
      CONCLUSION: There was a poor agreement between dye and bacterial leakage methods.
      Leakage results produced by nanosilver gutta-percha were comparable to those by
      standard gutta-percha. Considering the antibacterial effects of nanosilver coated
      gutta-percha, use of this type of gutta-percha might be more efficacious in
      endodontic treatments.

PMID- 23130069
TI  - Comparing Coronal Discoloration Between AH26 and ZOE Sealers.
AB  - INTRODUCTION: Intrinsic tooth discolorations after endodontic treatment are
      principally attributed to the composition of necrotic pulp tissue, hemorrhage
      within the pulp cavity, endodontic medicaments and/or filling materials. Residual
      sealer left in pulp chamber after obturation can cause discoloration. The
      objective of this in vitro study was to evaluate coronal discoloration created by
      AH26 and ZOE sealers after four months. MATERIALS AND METHODS: Fifty intact human
      extracted maxillary central incisors were employed. Access cavities were prepared
      in all samples and root canals were instrumented; coronal orifices were then
      sealed using self-cure glass ionomer. The teeth were divided into two
      experimental groups (n=20) according to utilized sealer in pulp chambers
      including AH26 and Dorifill (ZOE). The remaining 10 teeth served as negative and
      positive controls (n=5). The access cavities were sealed with self-cure glass
      ionomer. Teeth were kept in incubator for four month. Preliminary digital images
      of the teeth were taken and then compared with those related to 4-month follow
      up. The images were assessed using Photoshop software. Data was analyzed using
      paired t-test and independent samples t-test. RESULTS: The teeth which were
      filled with AH26 sealer showed significantly greater discoloration than those
      filled with ZOE sealer (Dorifill) (P<0.05). CONCLUSION: AH26 sealer causes
      greater discoloration of the crown compared to ZOE sealer. Despite the other
      disadvantage of AH26 sealer, it seems that Dorifill is more esthetically
      considerate.

PMID- 23130070
TI  - Comparison of two canal preparation techniques using mtwo rotary instruments.
AB  - INTRODUCTION: Root canal preparation is an important process in endodontic
      therapy. Nickel-titanium (NiTi) rotary file system can be used in single length
      technique (simultaneous technique) without early coronal enlargement, as well as
      in crown-down method. The purpose of this in vitro study was to compare single
      length with crown-down methods' shaping ability using Mtwo NiTi files. MATERIALS
      AND METHODS: Fifteen acrylic-resin blocks containing simulated canals were
      divided into two experimental groups. In group A, single length technique was
      used and in group B root canals were prepared by crown-down technique. Pre- and
      post-preparation canals were photographed in a standardized manner and were
      superimposed. The inner and outer walls of canal curvature were evaluated at
      three points (apical, middle and coronal) to determine the greatest change. The
      data was statistically analyzed using the Student t-test by Statistical Analysis
      System (SAS) software. RESULTS: Statistical analysis revealed that in group B,
      dentine was equally removed within the canal coronal to the curvature, whereas in
      group A, the inner wall was predominantly removed (P<0.01). The two groups had no
      significant difference at the apical and middle points of the canal curvature.
      CONCLUSION: Our in vitro study revealed no significant difference between the
      single length method and crown-down technique using Mtwo for preparation of
      apical and middle portion of canal curvature.

PMID- 23130071
TI  - Coronal microleakage for readymade and hand mixed temporary filling materials.
AB  - INTRODUCTION: The purpose of this in vitro study was to evaluate the sealing
      ability of the readymade temporary filling and hand mixed materials by assessing
      coronal microleakage. MATERIALS AND METHODS: Standardized access cavities were
      prepared in 80 intact human permanent premolar teeth. They were divided randomly
      into four experimental groups (n=20). The teeth were restored using one of the
      temporary materials including Cavisol, Litrak, Zinc phosphate cement, Zinconol
      (IRM). Thermocycling was applied on the specimens. Methylene blue dye was applied
      and penetration was evaluated under stereomicroscope. Grading of the microleakage
      pattern was from 1 to 3, with 3 providing the best seal. Results were analyzed
      using one-way ANOVA test (P<0.05). RESULTS: Microleakage of Cavisol and Litrak
      samples achieved grade 3; whereas zinc phosphate cement and Zinconol samples
      absorbed the dye into the bulk of the materials. Cavisol was found to exhibit the
      best seal amongst the four tested materials followed by Litrak, zinc phosphate
      cement, and Zinconol. There was a statistically significant difference in the
      microleakage scores obtained between the materials (P<0.01). CONCLUSION: Among
      the four materials tested, readymade temporary filling provided the best sealing
      ability over hand-mixed. This study emphasizes the importance of correct
      placement and sufficient thickness of temporary filling materials in endodontic
      access cavities to ensure a tight seal.

PMID- 23130072
TI  - Evaluation of the Doxycycline Release from AH26 Sealer-Doxycycline Combination:
      An ex vivo Study.
AB  - INTRODUCTION: The purpose of this ex vivo study was to determine the releasing
      characteristics and doxycycline dentinal diffusion of AH26 sealer-doxycycline
      combination from apical 3mm of tooth root and apical foramen. MATERIALS AND
      METHODS: One-hundred and two recently extracted single-rooted human teeth were
      decoronated and prepared with #3 and #4 Gates-Glidden drills and rotary Mtwo
      files. Smear layer was removed; all surfaces except for apical 3mm of each root
      were sealed with two coats of nail polish. To quantify the release and diffusion
      of the doxycycline at different time intervals (30 min, 48 and 72 h) after root
      canal obturation, the samples were randomly divided into three groups (n=30; 0.5
      h, 48 h, 72 h). To evaluate the release of doxycycline from AH26 sealer
      doxycycline combination at six concentrations of antibiotic including 0.5%, 1%,
      2%, 5%, 10% and 20%; each experimental group was divided into six equal subgroups
      (n=5). Root canals were filled with gutta-percha and AH26-doxycycline
      combinations and then were placed in vials containing 1.25mL of phosphate buffer
      saline solution (PBS). After 30 min, 48 and 72 h, the amount of doxycycline
      released from specimens into PBS were determined by measuring the absorbance
      values using UV spectrophotometry at lambda(max)=350 nm. Data were analyzed using
      two-way ANOVA. RESULTS: The findings of this study revealed that AH26 sealer
      doxycycline combination released variable measures of antibiotic at each time
      interval and in the various concentrations. At 30 min, no statistically
      significant differences were obtained between the results of subgroups, but at 48
      and 72 h these differences were significant (P<0.001). The results also showed
      that differences between 0.5 h, 48 h and 72 h were significant within subgroups
      (P<0.01). CONCLUSION: Under the conditions of this ex vivo study, doxycycline can
      be released from AH26 sealer-antibiotic combination through 3mm of apical root
      and apical foramen at 30 min, 48 and 72 h after mixing the sealer with
      doxycycline at concentrations of 0.5% up to 20%.

PMID- 23130073
TI  - A Survey on NiTi Rotary Instruments Usage by Endodontists and General Dentist in
      Tehran.
AB  - INTRODUCTION: The aim of this study was to assess the extent of adoption,
      application and the associated issues with the nickel-titanium (NiTi) rotary
      instruments and techniques amongst endodontists and general dentists in Tehran.
      MATERIALS AND METHODS: A total of 33 questions classified in six categories of
      demographics, frequency rate of NiTi rotary instrumentation and information. The
      sample size comprised of 100 endodontists and 100 general dental practitioners in
      Tehran. RESULTS: The overall response rate was 73.5%. NiTi rotary instruments
      were used by 98.4% and 50.6% of endodontists and general dentists, respectively.
      The main mentioned reason for not using rotary NiTi instruments was "lack of
      education". Among all procedural faults with NiTi, the most prevalent was "intra
      canal file fracture" (88.5%) followed by "apical transportation" (71.2%) and
      "ledging" (68.3%). The main factors associated with the first procedural accident
      were "over-use" and "excessive pressure". CONCLUSION: Dentists need more training
      and more comprehensive education regarding NiTi rotary instruments and
      techniques.

PMID- 23130074
TI  - Mandibular second premolars with three root canals: a review and 3 case reports.
AB  - Before initiating any endodontic therapy, probability of extra canals should be
      considered. The Incidence of three canals in mandibular second premolar has been
      reported to be 0.46-0.5%. The present report describes nonsurgical endodontic
      treatment of three mandibular second premolars with three canals. In these cases,
      three orifices were located in mesiobuccal, distobuccal and lingual. Mesiobuccal
      orifices were found after removing dentinal shelves. Even in teeth with extremely
      complex root canal morphologies, conventional endodontic treatment without
      surgical intervention can result in adequate healing, as in these cases.
      Clinicians should be aware of unusual root canal anatomy in mandibular premolars.
      Very careful examination of the pulpal space, preferably with an optical device
      is recommended to locate any unusual orifices.

PMID- 23130075
TI  - An In Vitro SEM Study on the Effectiveness of Smear Layer Removal of Four
      Different Irrigations.
AB  - INTRODUCTION: The aim of this study was to compare the smear layer removal
      efficacies of 3% sodium hypochlorite (NaOCl), 17% Ethylenediaminetetraacetic acid
      (EDTA), SmearClear and BioPure MTAD using a common irrigation protocol. MATERIALS
      AND METHODS: Fifty freshly extracted human single rooted maxillary and mandibular
      teeth were prepared by a ProTaper rotary system up to an apical preparation file
      size F3. Prepared teeth were randomly divided into five groups (n=10); distilled
      water (Group A; negative control), EDTA (Group B), SmearClear (Group C), BioPure
      MTAD (Group D) and NaOCl (Group E). After final irrigation with tested irrigants
      the teeth were decoronated, split into two halves longitudinally and observed
      under a scanning electron microscope (SEM) for removal of the smear layer. The
      SEM images were then analyzed for the amount of smear layer present using a three
      score system. Data were analyzed using the Kruskal-Wallis test and Mann-Whitney U
      test. RESULTS: Intergroup comparison of groups B, C, and D showed no statistical
      significant differences in the coronal and middle thirds, however, in the apical
      third the canal surfaces were cleaner in samples from group D (P<0.05).
      CONCLUSION: BioPure MTAD was the most effective agent for the purpose of smear
      layer removal in the apical third of the root canals.

PMID- 23130076
TI  - The effect of root canal preparation on the development of dentin cracks.
AB  - INTRODUCTION: Root fracture is not an instant phenomenon but a result of gradual
      development of tiny craze lines in tooth structure. Recent studies have shown
      that canal instrumentation has the potential to cause dentinal cracks. The
      purpose of this study was to evaluate and compare the formation of dentinal
      cracks caused by ProTaper rotary system to hand instrumentation. MATERIALS AND
      METHODS: This in vitro study was carried out using 57 mandible incisor teeth. The
      teeth were decoronated. The roots were then examined to exclude cracked samples.
      A standard model for PDL simulation was used. The teeth were randomly divided
      into two experimental and one control group (n=19). The teeth in the experimental
      groups were prepared using hand or ProTaper Universal rotary instrumentation. The
      teeth in the control group were left unprepared. The teeth were then sectioned
      horizontally 3 and 6 mm from the apex, and the number of various dentinal defects
      was recorded using a dental operating microscope. The differences between groups
      were analyzed with Fisher's exact test. RESULTS: The hand group demonstrated
      significantly more defects than the control group (P=0.001). However, there was
      no significant difference between the rotary compared to the control and hand
      groups (P>0.05). There was no significant difference between groups with regards
      to fracture (P>0.05). Other defects including internal, external and surface
      cracks were more frequent in the hand than in the control or rotary groups
      (P=0.02), but the difference was not significant between the rotary and control
      groups (P>0.05). CONCLUSION: Canal preparation, whether hand or rotary, produces
      structural defects in dentin. The ProTaper rotary system when used according to
      the manufacturer's instructions, tends to produce fewer cracks and can be
      considered a safe preparation technique.

PMID- 23130077
TI  - Efficacy of Two Rotary NiTi Instruments in Removal of Resilon/Epiphany Obturants.
AB  - INTRODUCTION: The success of endodontic retreatment is related to the complete
      removal of the obturation material from the root canal system. The aim of this
      study was to evaluate the efficacy of Mtwo R and ProTaper retreatment files in
      removing the Resilon/Epiphany system with or without chloroform during
      retreatment. MATERIALS AND METHODS: Sixty distal roots of first mandibular molars
      were prepared and laterally condensed with Resilon/Epiphany, then divided into
      four groups (15 each for retreatment): 1) Mtwo R/solvent; 2) Mtwo R; 3) ProTaper
      D/solvent; and 4) ProTaper D. The cleanliness of the canal walls was evaluated
      using radiography; a stereomicroscope and SEM. Data were subjected to ANOVA and
      Student's t-test. RESULTS: Neither rotary system performed better than the other
      when considering the whole root canal, with or without solvent. In the apical
      portion, ProTaper/solvent showed the best result (P<0.05). CONCLUSION: In
      Resilon/Epiphany retreatment cases, ProTaper/solvent was better in the apical
      portion; however when considering the whole canal, Mtwo R and the ProTaper D
      series had the same performance.

PMID- 23130078
TI  - A New Method for Evaluating the Diffusion of Ca(2+) and OH(-) Ions through
      Coronal Dentin into the Pulp.
AB  - INTRODUCTION: Ca(OH)(2)-containing/forming materials are conventionally used for
      indirect pulp-capping and are theoretically able to release Ca(2+) and OH(-) ions
      for hydrolytic dissociation. However, no evidence exists for ion diffusion
      through the remaining coronal dentin. The aim of this study was to design an
      innovative experimental set-up to test the ability of Ca(OH)(2)-containing and
      Ca(OH)(2)-forming pulp-capping materials to generate pulpward Ca(2) and OH(-) ion
      fluxes through coronal dentin after indirect pulp-capping in vitro. MATERIALS AND
      METHODS: Standardized class 1 cavities were prepared in erupted sound human
      molars. Pulp tissue was excised. A coronal Remaining Dentin Thickness (RTD) (1+/
      0.2 mm thick) was prepared within an occlusal-to-pulp cavity system (coronal RD
      system). The whole system/sample was treated with 17% EDTA to remove the smear
      layer and the external surface was covered by nail varnish. Indirect pulp-capping
      was performed on coronal RDT using a conventional pulp-capping material covered
      by a glass ionomer cement, a composite and nail varnish. Chemically different
      Ca(OH)(2) materials were used to test the reliability of the set-up. The leached
      Ca(2+) and OH(-) ions were measured using ion-selective electrodes after soaking
      for 3 hours, 24 hours, and 7 days in deionized water (10 mL, 37 degrees C).
      RESULTS: Calcium ions were detected and a rise in pH was observed in the treated
      water after a few hours for all tested materials. CONCLUSION: The experimental
      set-up proved to be an easy and effective method for testing the different
      Ca(OH)(2)-containing and Ca(OH)(2)-forming materials ability to induce a pulpward
      flux of calcium and hydroxyl ions through coronal remaining dentin after indirect
      pulp-capping. The new system will allow the screening of current pulp-capping
      materials.

PMID- 23130079
TI  - The dissolving ability of different organic solvents on three different root
      canal sealers: in vitro study.
AB  - INTRODUCTION: The purpose of this in vitro study was to evaluate three common
      gutta-percha solvents' effectiveness in dissolving three different types of root
      canal sealers. MATERIALS AND METHODS: The solubility of three different root
      canal sealers (AH Plus, Apexit Plus and Endoflas FS) was assessed in xylene,
      refined orange oil, tetrachloroethylene and distilled water (control). One
      hundred twenty samples of root canal sealers were prepared and then divided into
      three equal groups (n=40). Each group was further divided into four equal
      subgroups (n=10) for immersion in the respective solvents for a 10 minute
      immersion period. The mean amount of weight loss was determined for each material
      in each solvent during the specified immersion period, and the values were
      subjected to statistical analysis. RESULTS: Xylene exhibited the greatest
      dissolving efficacy for AH Plus, followed by refined orange oil and
      tetrachloroethylene. Xylene was also able to dissolve the greatest amount of
      Apexit Plus, followed by refined orange oil and tetrachloroethylene which were
      equally effective in dissolving Apexit Plus. For Endoflas FS, maximum dissolving
      efficacy was seen with tetrachloroethylene followed by refined orange oil and
      xylene. CONCLUSION: The results showed that xylene, refined orange oil and
      tetrachloroethylene can be used for the removal of AH Plus, Apexit plus and
      Endoflas FS sealers during endodontic retreatment. Further clinical
      investigations are needed to evaluate the efficacy of these solvents on different
      sealers.

PMID- 23130080
TI  - The multidisciplinary management of avulsed teeth: a case report.
AB  - This paper reports multidisciplinary treatment of a dental trauma case to achieve
      a favorable prognosis. A healthy 14-year-old girl reported avulsion of teeth 11
      and 21 which had occurred three months earlier. The initial treatment consisting
      of replantation with a semi-rigid splint was performed in hospital. At
      presentation, the patient was still using the semi-rigid splint. The clinical
      examination revealed the presence of increased mobility in teeth 11 and 21, and
      absence of vitality in both. Radiographic examination showed the presence of
      inflammatory external root resorption in both teeth. The treatment proposed
      consisted of teeth extraction, a temporary prosthesis followed by adhesive
      prosthesis, and finally, implant surgery associated with porcelain crowns.

PMID- 23130081
TI  - Mandibular first premolar with three roots: a case report.
AB  - Anatomy of the root canal system always effects endodontic treatment outcome.
      Mandibular premolar teeth show extreme variations in root canal morphology. First
      premolars usually exhibit basic one root and one canal anatomy. The occurrence of
      three roots in mandibular first premolar has not been commonly reported in
      literature. This article reports a case of successful nonsurgical endodontic
      management of mandibular first premolar with three canals and three different
      apical foramina.

PMID- 23130082
TI  - Non-Surgical Repair of Internal Resorption with MTA: A Case Report.
AB  - Internal resorption is rare in permanent teeth. Treatment is usually performed
      through warm gutta-percha technique. If the resorptive process perforates the
      root, treatment may be more difficult and is usually performed via surgical
      approach. Non-surgical repair of a perforating internal root resorption with MTA
      was conducted in this case. Before repairing the resorption, a master gutta
      percha point was placed in the canal to maintain negotiability of the original
      canal path. Then, MTA was prepared and applied with a small carrier in the
      resorption area and compacted. Thereafter gutta-percha was retrieved and the
      access cavity was closed with a temporary filling material. In the second visit,
      the root canal was obturated with gutta-percha and AH26 sealer using lateral
      compaction technique and subsequently, the crown was restored. The symptoms and
      signs ceased and the result was satisfactory at the 18 month follow-up visit.

PMID- 23130083
TI  - Two rooted maxillary lateral incisor: a case report.
AB  - An accurate diagnosis of the morphology of the root canal system is a pre
      requisite for successful root canal treatment. Frequently, root canals are left
      untreated because the clinicians fail to identify their presence, particularly in
      teeth that have anatomical variations or additional root canals. In this report a
      maxillary lateral incisor with two roots has been described.

PMID- 23130084
TI  - Nanostructure-templated control of drug release from peptide amphiphile nanofiber
      gels.
AB  - High aspect ratio peptide nanofibers have potential as biodegradable vehicles for
      drug delivery. We report here the synthesis of four self-assembling peptide
      amphiphiles (PAs) containing a lysine epsilon-amine-derivatized hydrazide that
      was systematically placed at different positions along the backbone of the
      peptide sequence C(16)V(2)A(2)E(2) (where C(16) = palmitic acid). Hydrazones were
      formed from each hydrazide by condensation with the solvatochromic dye 6
      propionyl-2-dimethylaminonaphthalene (Prodan), which is typically used to probe
      cell membranes. All four compounds were found to self-assemble into nanofibers,
      and Prodan release was measured from filamentous gels prepared by screening PA
      charges with divalent cations. Near zero-order release kinetics were observed for
      all nanofibers, but release half-lives differed depending on the position of the
      fluorophore in the PA sequence. Dye release kinetics were rationalized through
      the use of cryogenic transmission electron microscopy, small-angle X-ray
      scattering, fluorescence spectroscopy, fluorescence anisotropy, circular
      dichroism, and partition coefficient calculations. Relative release rates were
      found to correlate directly with fluorophore mobility, which varied inversely
      with packing density, degree of order in the hydrophobic PA core, and the beta
      sheet character of the peptide.

PMID- 23130085
TI  - Do Social Attribution Skills Improve with Age in Children with High Functioning
      Autism Spectrum Disorders?
AB  - Age-related changes in social attribution skills were assessed using the
      "Triangles Playing Tricks" task in 7-17 year old high functioning children with
      ASDs (n=41) and in typically developing (TD) children (n=58) matched on age, IQ,
      and sex ratio. Children with ASDs gave responses that received lower
      intentionality and appropriateness ratings than did TD children in both the goal
      directed and theory of mind (ToM) conditions. Results remained unchanged when the
      effects of verbal output (i.e., number of clause produced) and verbal IQ were
      included as covariates in the analyses. Whereas age was highly associated with
      ToM performance in the TD children, this relationship was not as strong among
      children with ASDs. These results indicate not only a diminished tendency among
      high functioning children with ASDs to attribute social meaning and
      intentionality to ambiguous visual displays of interactive forms but also an
      aberrant developmental trajectory. That is, children with ASDs may fall further
      behind their typically developing peers in social attribution abilities as they
      get older.

PMID- 23130087
TI  - Low-dose "metronomic chemotherapy" with oral cyclophosphamide and methotrexate in
      metastatic breast cancer: a case report of extraordinarily prolonged clinical
      benefit.
AB  - We report the case of a 34-year-old woman affected by breast cancer that had
      metastasized to the bone. She had been treated with oral cyclophosphamide and
      methotrexate (metronomic chemotherapy) and achieved 3.5 years of clinical
      remission. To our knowledge, this is the first description of such a prolonged
      response to therapy. This case report adds weight to known data on metronomic
      treatment and supports further investigation of this therapy.

PMID- 23130086
TI  - Corpus Callosum Area in Children and Adults with Autism.
AB  - Despite repeated findings of abnormal corpus callosum structure in autism, the
      developmental trajectories of corpus callosum growth in the disorder have not yet
      been reported. In this study, we examined corpus callosum size from a
      developmental perspective across a 30-year age range in a large cross-sectional
      sample of individuals with autism compared to a typically developing sample.
      Midsagittal corpus callosum area and the 7 Witelson subregions were examined in
      68 males with autism (mean age 14.1 years; range 3-36 years) and 47 males with
      typical development (mean age 15.3 years; range 4-29 years). Controlling for
      total brain volume, increased variability in total corpus callosum area was found
      in autism. In autism, increased midsagittal areas were associated with reduced
      severity of autism behaviors, higher intelligence, and faster speed of processing
      (p=0.003, p=0.011, p=0.013, respectively). A trend toward group differences in
      isthmus development was found (p=0.029, uncorrected). These results suggest that
      individuals with autism benefit functionally from increased corpus callosum area.
      Our cross-sectional examination also shows potential maturational abnormalities
      in autism, a finding that should be examined further with longitudinal datasets.

PMID- 23130088
TI  - Psychological trauma in soldiers-a challenge for the German Armed Forces
      (Bundeswehr).

PMID- 23130089
TI  - Traumatic experiences and posttraumatic stress disorder in soldiers following
      deployment abroad: how big is the hidden problem?
AB  - BACKGROUND: Little is known about the frequency of traumatic event exposure and
      the development of post-traumatic stress disorder (PTSD) among German soldiers
      serving in Afghanistan. METHODS: We studied a random sample consisting of 1599
      soldiers who had served in the 2009/2010 ISAF mission in Afghanistan, stratified
      by deployment location and unit. Twelve months after their return to Germany, the
      soldiers were assessed with a Composite International Diagnostic Interview (CIDI)
      to establish the diagnoses of mental disorders and PTSD according to the DSM-IV.
      889 similar soldiers who had not been deployed abroad were assessed in the same
      way. RESULTS: 49.2% (95% confidence interval [CI]: 46.4 to 52.1) of the deployed
      soldiers experienced at least one traumatic event during their deployment, and
      13% experienced more than three. The 12-month prevalence of PTSD among returning
      soldiers was 2.9% (95% CI: 2.1 to 4.1), while the service-related incidence after
      deployment was 0.9% (95% CI: 0.5 to 1.6). These figures imply a two- to fourfold
      elevation of the risk of PTSD. The risk of PTSD was highest among soldiers who
      had served in Kunduz (Afghanistan) and in combat units. Only half of all soldiers
      with PTSD sought professional help. CONCLUSION: Deployment abroad is associated
      with a high frequency of traumatic experiences and a two- to fourfold elevation
      of the risk of PTSD. Each year, about 300 cases of PTSD develop for every 10 000
      soldiers who return to Germany; thus, the cumulative number of returnees with
      PTSD from the beginning of German deployment abroad may currently run into the
      thousands. 45% of all PTSD cases, or about one in two, are neither diagnosed nor
      treated. Deployment abroad also substantially increases the risk of developing a
      number of other mental disorders.

PMID- 23130090
TI  - Deployment-related stress disorder in german soldiers: utilization of psychiatric
      and psychotherapeutic treatment.
AB  - INTRODUCTION: Military missions abroad carry a high risk of psychological
      traumatization. In this study, we examined the reasons for increased utilization
      of the treatments offered to soldiers by the German armed forces' psychiatric
      services. METHOD: We analyzed trends in initial contacts with psychiatrists and
      psychotherapists among German soldiers participating in missions to Afghanistan
      and the Balkans. To this end, we evaluated existing data from the psychiatric
      services of all German Armed Forces Military Hospitals with respect to
      sociodemographic factors (sex, area of mission) and the underlying psychiatric
      disorders over an 18-month period (January 2010 to June 2011). RESULTS: 615
      soldiers made an initial contact with the psychiatric and psychotherapeutic
      services during the study period. The total number of first contacts did not
      change significantly (p = 0.195), but there was a notable rise in the number of
      first contacts by female soldiers with deployment-related stress (p = 0.003).
      Mission-specific statistics revealed a significant increase in the number of
      first contacts only for soldiers deployed to the Balkans (p = 0.017). 91% of
      soldiers making a first contact were given the diagnosis of a stress reaction
      (ICD-10: F 43); the second most common diagnosis (8.9%) was an affective disorder
      (ICD-10: F 32.0, F 32.1). CONCLUSION: Despite psychological prevention efforts,
      military missions abroad often lead to mental disorders. Our findings indicate
      that the mild observed increase in incidence is both sex-specific and deployment
      area-specific.

PMID- 23130091
TI  - Correspondence (letter to the editor): Local antibiotic therapy was not given
      enough space.

PMID- 23130093
TI  - The Zero-truncated Poisson with Right Censoring: an Application to Translational
      Breast Cancer Research.
AB  - We propose to analyze positive count data with right censoring from Behbod et al.
      (2009) using the censored zero-truncated Poisson model (CZTP). The comparison in
      truncated means across subgroups in each cell line is carried out through a log
      linear model that links the un-truncated Poisson parameter and regression
      covariates. We also perform simulation to evaluate the performance of the CZTP
      model in finite and large sample sizes. In general, the CZTP model provides
      accurate and precise estimates. However, for data with small means and small
      sample sizes, it may be more proper to make inference based on the mean counts
      rather than on the regression coefficients. For small sample sizes and moderate
      means, the likelihood ratio test is more reliable than the Wald test. We also
      demonstrate how power analysis can be used to justify and/or guide the choice of
      censoring thresholds in study design. A SAS macro is provided in Appendix for
      readers' reference.

PMID- 23130095
TI  - What is pulmonary arterial hypertension?

PMID- 23130096
TI  - Is surgical treatment the cure for patients with congenital heart disease?

PMID- 23130094
TI  - Fear of memories: the nature of panic in posttraumatic stress disorder.
AB  - BACKGROUND: Although there is increasing evidence that panic attacks are common
      in posttraumatic stress disorder (PTSD), little is known if posttraumatic panic
      is comparable to panic attacks observed in panic disorder (PD). OBJECTIVE: This
      study examined the cognitive responses to panic attacks in participants with PD
      and PTSD. METHOD: Participants with PD (n=22) and PTSD (n=18) were assessed on
      the Anxiety Disorder Interview Schedule for DSM-IV and subsequently administered
      the Agoraphobic Cognitions Questionnaire and a measure of fears related to trauma
      memories. RESULTS: Although participants did not differ in terms of catastrophic
      appraisals about somatic sensations, PTSD participants were more likely to
      experience fears about trauma memories and being harmed by trauma again during
      their panic attacks than PD participants. CONCLUSIONS: These findings suggest
      that although PTSD participants fear somatic outcomes during panic attacks, their
      panic attacks are distinguished by a marked fear of trauma memories.

PMID- 23130097
TI  - Are men at risk? The role of testosterone in cardiovascular morbidity.

PMID- 23130098
TI  - Holding our breath: The emerging and anticipated roles of microRNA in pulmonary
      hypertension.
AB  - Over the past decade, the importance of non-coding RNA such as microRNA has been
      established in numerous processes that drive human pathogenesis. These crucial
      molecular regulators modulate networks of target gene transcripts that, in turn,
      orchestrate cellular phenotypes such as cell survival, differentiation,
      proliferation, and metabolism among others and thus affect cardiopulmonary
      vascular disease conditions. Many of these same pathophenotypes figure
      prominently in the complex pathogenesis of pulmonary hypertension, an enigmatic
      vascular disorder characterized by a histological panvasculopathy and driven by
      disparate upstream triggers such as hypoxia, inflammation, and bone morphogenetic
      protein signaling. Yet, the importance of just a few microRNAs in pulmonary
      hypertension has been recognized, and we are only beginning to understand the
      integrative functions of these molecules in this disease. By combining systems
      biology with traditional experimental approaches, more direct insight into the
      pleiotropy of microRNA should not only further reveal the spectrum of molecular
      pathways that cause pulmonary hypertension, but also offer novel and much needed
      diagnostic and therapeutic strategies.

PMID- 23130099
TI  - Platelets in pulmonary vascular physiology and pathology.
AB  - Almost a trillion platelets pass through the pulmonary circulation every minute,
      yet little is known about how they support pulmonary physiology or contribute to
      the pathogenesis of lung diseases. When considering this conundrum, three
      questions jump out: Does platelet production in the lungs occur? Why does severe
      thrombocytopenia-which undercuts the principal physiological role of platelets to
      effect hemostasis-not lead to pulmonary hemorrhage? Why does atherothrombosis
      which platelets initiate, maintain, and trigger is other critically important
      arterial beds-not develop in the pulmonary artery? The purpose of this review is
      to explore these and derivative questions by providing data within a conceptual
      framework that begins to organize a subject that is largely unassembled.

PMID- 23130100
TI  - Right ventricular plasticity and functional imaging.
AB  - Right ventricular (RV) function is a strong independent predictor of outcome in a
      number of distinct cardiopulmonary diseases. The RV has a remarkable ability to
      sustain damage and recover function which may be related to unique anatomic,
      physiologic, and genetic factors that differentiate it from the left ventricle.
      This capacity has been described in patients with RV myocardial infarction,
      pulmonary arterial hypertension, and chronic thromboembolic disease as well as
      post-lung transplant and post-left ventricular assist device implantation.
      Various echocardiographic and magnetic resonance imaging parameters of RV
      function contribute to the clinical assessment and predict outcomes in these
      patients; however, limitations remain with these techniques. Early diagnosis of
      RV function and better insight into the mechanisms of RV recovery could improve
      patient outcomes. Further refinement of established and emerging imaging
      techniques is necessary to aid subclinical diagnosis and inform treatment
      decisions.

PMID- 23130102
TI  - Altered expression of nuclear and cytoplasmic histone H1 in pulmonary artery and
      pulmonary artery smooth muscle cells in patients with IPAH.
AB  - The pathogenesis of idiopathic pulmonary hypertension is poorly understood. This
      paper utilized histology-based Matrix-Assisted Laser Desorption Ionization Mass
      Spectrometry (MALDI MS) to identify as-yet unknown proteins that may be
      associated with the structural changes in the pulmonary arterial walls of
      patients with IPAH. The technology identified significant increases in two
      fragments of histone H1 in the IPAH cases compared to controls. This finding was
      further examined using immunofluorescence techniques applied to sections from
      IPAH and control pulmonary arteries. In addition, cultured pulmonary artery
      smooth muscle cells (PASMCs) were utilized for Western analysis of histone H1 and
      importin beta and importin 7, immunoprecipitation and assessment of nucleosomal
      repeat length (NRL). Immunofluorescence techniques revealed that nuclear
      expression of histone H1 was decreased and the chromatin was less compact in the
      IPAH cases than in the controls; furthermore, some cases showed a marked increase
      in cytoplasmic histone H1 expression. Using nuclear and cytoplasmic fractions of
      cultured PASMCs, we confirmed the reduction in histone H1 in the nucleus and an
      increase in the cytoplasm in IPAH cells compared to controls. Immunoprecipitation
      demonstrated a decreased association of histone H1 with importin beta while
      importin 7 was unchanged in the IPAH cells compared to controls. The assessment
      of NRL revealed that the distance between nucleosomes was increased by ~20 bp in
      IPAH compared to controls. We conclude that at least two factors contribute to
      the reduction in nuclear histone H1-fragmentation of the protein and decreased
      import of histone H1 into the nucleus by importins. We further suggest that the
      decreased nuclear H1 contributes the less compact nucleosomal pattern in IPAH and
      this, in turn, contributes to the increase in NRL.

PMID- 23130101
TI  - Pulmonary blood flow and pulmonary hypertension: Is the pulmonary circulation
      flowophobic or flowophilic?
AB  - Increased pulmonary blood flow (PBF) is widely thought to provoke pulmonary
      vascular obstructive disease (PVO), but the impact of wall shear stress in the
      lung is actually poorly defined. We examined information from patients having
      cardiac lesions which impact the pulmonary circulation in distinct ways, as well
      as experimental studies, asking how altered hemodynamics impact the risk of
      developing PVO. Our results are as follows: (1) with atrial septal defect (ASD;
      increased PBF but low PAP), shear stress may be increased but there is little
      tendency to develop PVO; (2) with normal PBF but increased pulmonary vascular
      resistance (PVR; mitral valve disease) shear stress may also be increased but
      risk of PVO still low; (3) with high PVR and PBF (e.g., large ventricular septal
      defect), wall shear stress is markedly increased and the likelihood of developing
      PVO is much higher than with high PBF or PAP only; and (4) with ASD, experimental
      and clinical observations suggest that increased PBF plus another stimulus (e.g.,
      endothelial inflammation) may be required for PVO. We conclude that modestly
      increased wall shear stress (e.g., ASD) infrequently provokes PVO, and likely
      requires other factors to be harmful. Likewise, increased PAP seldom causes PVO.
      Markedly increased wall shear stress may greatly increase the likelihood of PVO,
      but we cannot discriminate its effect from the combined effects of increased PAP
      and PBF. Finally, the age of onset of increased PAP may critically impact the
      risk of PVO. Some implications of these observations for future investigations
      are discussed.

PMID- 23130103
TI  - Testosterone negatively regulates right ventricular load stress responses in
      mice.
AB  - Right ventricular (RV) function is the major determinant of mortality in
      pulmonary arterial hypertension and male sex is a strong predictor of mortality
      in this disease. The effects of testosterone on RV structure and function in load
      stress are presently unknown. We tested whether testosterone levels affect RV
      hypertrophic responses, fibrosis, and function. Male C57BL/6 mice underwent
      castration or sham followed by pulmonary artery banding (PAB) or sham. After
      recovery, testosterone pellets were placed in a subset of the castrated mice and
      mice were maintained for at least two weeks, when they underwent hemodynamic
      measurements and tissues were harvested. Plasma levels of testosterone were
      reduced by castration and repleted by testosterone administration. In PAB,
      castration resulted in lower right ventricle/left ventricle + septum (RV/LV+S),
      and myocyte diameter (P < 0.05). Replacement of testosterone normalized these
      parameters and increased RV fibrosis (P < 0.05). Two weeks of PAB resulted in
      increased RV systolic pressure in all groups with decreased markers of RV
      systolic and diastolic function, specifically reduced ejection fraction and
      increased time constant, and dPdt minimum (P < 0.05), though there was minimal
      effect of testosterone on hemodynamic parameters. Survival was improved in mice
      that underwent castration with PAB compared with PAB alone (P < 0.05).
      Testosterone affects RV hypertrophic response to load stress through increased
      myocyte size and increased fibrosis in mice. Castration and testosterone
      replacement are not accompanied by significant alterations in RV in vivo
      hemodynamics, but testosterone deprivation appears to improve survival in PAB.
      Further study of the role of testosterone in RV dysfunction is warranted to
      better understand these findings in the context of human disease.

PMID- 23130104
TI  - An Australian tertiary referral center experience of the management of chronic
      thromboembolic pulmonary hypertension.
AB  - The objective of this study was to report the outcome of pulmonary endarterectomy
      (PEA) surgery performed for chronic thromboembolic pulmonary hypertension (CTEPH)
      at a single tertiary center. The prospective study consisted of 35 patients with
      surgically amenable CTEPH undergoing PEA between September 2004 and September
      2010. The main outcome measures were Functional (New York Heart Association
      [NYHA] class, 6-Minute Walk Distance), hemodynamic (echocardiography, right heart
      catheterization, and cardiac MRI), and outcome data (morbidity and mortality).
      Following PEA, there were significant improvements in NYHA class (pre 2.9+/-0.7
      vs. post 1.3+/-0.5, P < 0.0001), right ventricular systolic pressure (pre 77.4+/
      24.8 mmHg vs. post 45.1+/-24.9 mmHg, P = 0.0005), 6-Minute Walk Distance (pre
      419.6+/-109.4 m vs. post 521.6+/-83.5 m, P = 0.0017), mean pulmonary artery
      pressure (pre 41.8+/-15.3 mmHg vs. post 24.7+/-8.8 mmHg, P = 0.0006), and cardiac
      MRI indices (end diastolic volume pre 213.8+/-49.2 mL vs. post 148.1+/-34.5 mL, P
      < 0.0001; ejection fraction pre 40.7+/-9.8 mL vs. post 48.1+/-8.9 mL, P =
      0.0069). The mean cardiopulmonary bypass time was 258.77+/-26.16 min, with a mean
      circulatory arrest time of 43.83+/-28.78 min, a mean ventilation time of 4.7+/
      7.93 days (range 0.2-32.7), and a mean intensive care unit stay of 7.22+/-8.71
      days (range 1.1-33.8). Complications included reperfusion lung injury (20%),
      persistent pulmonary hypertension (17.1%), slow respiratory wean (25.7%),
      pericardial effusion (11.4%), and cardiac tamponade (5.7%). 1-year mortality post
      procedure was 11.4%. Pulmonary endarterectomy can be performed safely with
      relatively low mortality.

PMID- 23130105
TI  - Comparison of 18F-FDG uptake by right ventricular myocardium in idiopathic
      pulmonary arterial hypertension and pulmonary arterial hypertension associated
      with congenital heart disease.
AB  - This study measured glucose uptake in the right ventricle (RV) of patients with
      pulmonary hypertension and investigated the relationship to hemodynamics and
      survival. Myocardial 18F-fluorodeoxy-glucose (FDG) uptake was measured using
      single-photon positron emission tomography (SPECT) in 24 patients with idiopathic
      pulmonary arterial hypertension (IPAH) and 43 patients with congenital heart
      disease (CHD). In both IPAH and CHD-PAH, RV FDG uptake (RV/LV ratio) was
      associated with pulmonary vascular resistance (PVR). A second SPECT scan was
      performed in nine patients after 6 months treatment with sildenafil. PVR
      decreased from 1683+/-426 to 1207+/-383 dyn s(-1) cm(-5) (P < 0.05) and cardiac
      index improved from 2.2+/-0.2 to 2.8+/-0.5 L/min/m(2) (P < 0.01). RV/LV FDG
      uptake decreased from 1.28+/-0.32 before treatment to 0.99+/-0.23 (P < 0.05).
      Survival in the IPAH group with a baseline RV/LV FDG uptake greater than the
      median value of 1.20 was significantly lower than that of the group with RV/LV
      FDG uptake below 1.20 (log-rank test, P < 0.05). In contrast, baseline RV/LV FDG
      was of little informative value in CHD. FDG uptake by the RV reflects the
      severity of PVR in PAH. Increased RV FDG uptake is a marker of poor prognosis in
      IPAH and is reduced in patients receiving effective therapy. It could prove
      useful in the early clinical assessment of novel therapies for PAH.

PMID- 23130106
TI  - The impact of pulmonary arterial hypertension-targeted therapy on survival in
      Chinese patients with idiopathic pulmonary arterial hypertension.
AB  - The survival rates of Chinese patients with idiopathic pulmonary arterial
      hypertension (IPAH) and familial pulmonary arterial hypertension (PAH) on
      conventional therapy at 1 and 3 years were 68.0% and 38.9%, respectively. Our aim
      was to update recent knowledge on the demographics, clinical course, hemodynamic
      features, disease management, and survival of adult patients with IPAH. This
      retrospective and observational study was conducted at the largest tertiary
      referral center in China. Ninety patients with IPAH who underwent initial
      evaluation at Fu Wai Hospital from January 2006 through November 2009 were
      retrospectively enrolled. The primary outcome was death. Statistical analyses
      used included independent sample t test, nonparametric test, Kaplan-Meier method,
      and Cox proportional hazards analysis. Of the 90 patients enrolled, the median
      age was 32 years with female predominance. The median interval from onset of
      symptoms to diagnosis was 14 months. Patients exhibited severe exercise
      limitation and hemodynamic abnormalities at diagnosis. Only 10.6% had a positive
      vasoreactivity test, while calcium channel blockers were given to 22.2% of
      patients. Fifty-nine patients (65.6%) received PAH-targeted therapies during
      follow-up. Our survival rates of 84.1%, 73.7%, and 70.6% at 1-, 2-, and 3-years
      compared favorably with predicted survival based on the National Institutes of
      Health equation which showed 1-, 2-, and 3-years survival rates of 67.7%, 55.9%,
      and 47%, respectively. For the patients receiving conventional therapy solely,
      the 1- and 3-years survival rates were 67.0% and 49.3%, respectively. Younger
      age, lower body mass index, presence of pericardial effusion, and absence of PAH
      targeted therapy were independently associated with mortality. We concluded that
      patients with IPAH were still diagnosed too late, and while survival rates have
      improved in the modern treatment era, there is still room for improvement.

PMID- 23130108
TI  - Cardiopulmonary exercise testing reveals onset of disease and response to
      treatment in a case of heritable pulmonary arterial hypertension.
AB  - Patients affected by pulmonary arterial hypertension (PAH) show a typical pattern
      of abnormalities on cardiopulmonary exercise testing (CPET). However, CPET is not
      routinely used as a screening method. We discuss a patient with hereditary PAH in
      whom CPET revealed onset of disease. Furthermore, we show that the abnormalities
      observed can improve in part by PAH-specific treatment.

PMID- 23130107
TI  - The renin-angiotensin system and right ventricular structure and function: The
      MESA-Right Ventricle Study.
AB  - The pulmonary vasculature is an important site of renin-angiotensin metabolism.
      While angiotensin-converting enzyme inhibitors and angiotensin II receptor
      blockers (collectively AIABs) have a role in left ventricular (LV) disease, the
      impact of AIABs on right ventricular (RV) function is unknown. AIAB use was
      determined by medication inventory during the Multi-Ethnic Study of
      Atherosclerosis baseline examination. RV measures were obtained via cardiac
      magnetic resonance imaging. The relationship between AIAB use and RV measures was
      assessed using multivariable linear regression, stratified by race/ethnicity, and
      adjusted for multiple covariates. AIAB use was associated with lower RV mass (
      0.7 g, 95% confidence interval [CI] -1.3 to -0.1, P=0.03) in African Americans
      (N=1012) after adjustment for multiple covariates including LV mass. Among
      Caucasians (N=1591), AIAB use was associated with larger RV end-diastolic volume
      (3.7 mL, 95% CI 0.7-6.8, P=0.02) after adjustment for LV volume. No significant
      associations were seen between AIAB use and other RV measures or in Hispanic or
      Chinese American participants. AIAB use was associated with RV morphology in a
      race-specific and LV-independent manner, suggesting the renin-angiotensin system
      may play a unique role in RV structure and function. The use of AIABs in those
      with RV dysfunction warrants further study.

PMID- 23130109
TI  - Takotsubo cardiomyopathy after treatment of pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension is a fatal disease. Intravenous prostanoids are
      often utilized for long-term management of patients. The therapy requires a
      significant commitment and change in lifestyle for both the patient and family.
      Takotsubo cardiomyopathy, transient apical ballooning syndrome, has been reported
      in association with emotional and physical stress. This case report describes a
      patient with pulmonary arterial hypertension who developed Takotsubo
      cardiomyopathy after treatment initiation with intravenous treprostinil. Over
      time, the syndrome resolved and the patient had return of normal left ventricular
      function. Takotsubo cardiomyopathy should be recognized as a potential, rare
      complication of therapy initiation due to the severity of the illness and the
      emotional stress of the disease.

PMID- 23130111
TI  - JAHA: The American Heart Association's Open Access Journal.

PMID- 23130112
TI  - Hyperlipidemia as an instigator of inflammation: inaugurating new approaches to
      vascular prevention.

PMID- 23130113
TI  - Power of national institutes of health stroke scale in assessing stroke systems
      of care.

PMID- 23130114
TI  - Mortality rates in trials of subjects with type 2 diabetes.
AB  - BACKGROUND: In randomized controlled trials (RCTs) of subjects with type 2
      diabetes mellitus, mortality rates vary substantially. We sought to examine the
      inclusion and exclusion criteria of these RCTs to explore relationships with
      mortality. METHODS AND RESULTS: MEDLINE database was searched from August 1980
      through March 2011. Selection criterion included published RCTs of adults with
      type 2 diabetes mellitus of at least 1000 patients, reporting all-cause mortality
      and having follow-up duration of at least 1 year. Twenty-two trials were
      eligible. Annualized mortality rates were derived. Inclusion and exclusion
      criteria were tabulated for each trial. Trials were categorized in 4 groups
      according to annual mortality rates: <1, >=1 to <2, >=2 to <4, and >=4 per 100
      patient-years. The analysis cohort included 91842 patients and 6837 deaths.
      Mortality rates ranged from 0.28 to 8.24 per 100 patient-years. Patients enrolled
      in the highest mortality category were more likely to be older and had longer
      diabetes duration and higher blood pressure. The selection for hypertension was
      common in the low- as well as high-mortality trials. Although the mortality rates
      were higher in RCTs with prior cardiovascular morbidity, the selection for
      chronic kidney disease-defined by either higher serum creatinine or lower
      estimated glomerular filtration rate and/or the presence of proteinuria-was
      associated with the highest mortality rates. CONCLUSIONS: In this analysis of
      RCTs of type 2 diabetes mellitus, a 29-fold difference in annualized mortality
      was observed. In these RCTs, selection for renal disease, defined by either
      decline in renal function or presence of proteinuria, portends important
      mortality risk. (J Am Heart Assoc. 2012;1:8-15.) CLINICAL TRIAL REGISTRATION:
      URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00303979.

PMID- 23130115
TI  - Incremental Reduction in Risk of Death Associated With Use of Guideline
      Recommended Therapies in Patients With Heart Failure: A Nested Case-Control
      Analysis of IMPROVE HF.
AB  - BACKGROUND: Several therapies are guideline-recommended to reduce mortality in
      patients with heart failure (HF) and reduced left ventricular ejection fraction,
      but the incremental clinical effectiveness of these therapies has not been well
      studied. We aimed to evaluate the individual and incremental benefits of
      guideline-recommended HF therapies associated with 24-month survival. METHODS AND
      RESULTS: We performed a nested case-control study of HF patients enrolled in
      IMPROVE HF. Cases were patients who died within 24 months and controls were
      patients who survived to 24 months, propensity-matched 1:2 for multiple
      prognostic variables. Logistic regression was performed, and the attributable
      mortality risk from incomplete application of each evidence-based therapy among
      eligible patients was calculated. A total of 1376 cases and 2752 matched controls
      were identified. beta-Blocker and cardiac resynchronization therapy were
      associated with the greatest 24-month survival benefit (adjusted odds ratio for
      death 0.42, 95% confidence interval (CI), 0.34-0.52; and 0.44, 95% CI, 0.29-0.67,
      respectively). Angiotensin-converting enzyme inhibitors/angiotensin receptor
      blockers, implantable cardioverter-defibrillators, anticoagulation for atrial
      fibrillation, and HF education were also associated with benefit, whereas
      aldosterone antagonist use was not. Incremental benefits were observed with each
      successive therapy, plateauing once any 4 to 5 therapies were provided (adjusted
      odds ratio 0.31, 95% CI, 0.23-0.42 for 5 or more versus 0/1, P<0.0001).
      CONCLUSIONS: Individual, with a single exception, and incremental use of
      guideline-recommended therapies was associated with survival benefit, with a
      potential plateau at 4 to 5 therapies. These data provide further rationale to
      implement guideline-recommended HF therapies in the absence of contraindications
      to patients with HF and reduced left ventricular ejection fraction. (J Am Heart
      Assoc. 2012;1:16-26.).

PMID- 23130116
TI  - Effector Memory T cells Are Associated With Atherosclerosis in Humans and Animal
      Models.
AB  - BACKGROUND#ENTITYSTARTX02014;: Adaptive T-cell response is promoted during
      atherogenesis and results in the differentiation of naive CD4(+)T cells to
      effector and/or memory cells of specialized T-cell subsets. Aim of this work was
      to investigate the relationship between circulating CD4(+)T-cell subsets and
      atherosclerosis.  METHODS AND RESULTS#ENTITYSTARTX02014;: We analyzed 57 subsets
      of circulating CD4(+)T cells by 10-parameter/8-color polychromatic flow cytometry
      (markers: CD3/CD4/CD45RO/CD45RA/CCR7/CCR5/CXCR3/HLA-DR) in peripheral blood from
      313 subjects derived from 2 independent cohorts. In the first cohort of subjects
      from a free-living population (n=183), effector memory T cells (T(EM):
      CD3(+)CD4(+)CD45RA(-)CD45RO(+)CCR7(-) cells) were strongly related with intima
      media thickness of the common carotid artery, even after adjustment for age
      (r=0.27; P<0.001). Of note, a significant correlation between T(EM) and low
      density lipoproteins was observed. In the second cohort (n=130), T(EM) levels
      were significantly increased in patients with chronic stable angina or acute
      myocardial infarction compared with controls. HLA-DR(+)T(EM) were the T(EM)
      subpopulation with the strongest association with the atherosclerotic process
      (r=0.37; P<0.01). Finally, in animal models of atherosclerosis, T(EM) (identified
      as CD4(+)CD44(+)CD62L(-)) were significantly increased in low-density lipoprotein
      receptor and apolipoprotein E deficient mice compared with controls and were
      correlated with the extent of atherosclerotic lesions in the aortic root (r=0.56;
      P<0.01).  CONCLUSIONS#ENTITYSTARTX02014;: Circulating T(EM) cells are associated
      with increased atherosclerosis and coronary artery disease in humans and in
      animal models and could represent a key CD4(+)T-cell subset related to the
      atherosclerotic process. (J Am Heart Assoc. 2012;1:27-41.).

PMID- 23130117
TI  - Relationship of national institutes of health stroke scale to 30-day mortality in
      medicare beneficiaries with acute ischemic stroke.
AB  - BACKGROUND: The National Institutes of Health Stroke Scale (NIHSS), a well
      validated tool for assessing initial stroke severity, has previously been shown
      to be associated with mortality in acute ischemic stroke. However, the
      relationship, optimal categorization, and risk discrimination with the NIHSS for
      predicting 30-day mortality among Medicare beneficiaries with acute ischemic
      stroke has not been well studied. METHODS AND RESULTS: We analyzed data from
      33102 fee-for-service Medicare beneficiaries treated at 404 Get With The
      Guidelines-Stroke hospitals between April 2003 and December 2006 with NIHSS
      documented. The 30-day mortality rate by NIHSS as a continuous variable and by
      risk-tree determined or prespecified categories were analyzed, with
      discrimination of risk quantified by the c-statistic. In this cohort, mean age
      was 79.0 years and 58% were female. The median NIHSS score was 5 (25th to 75th
      percentile 2 to 12). There were 4496 deaths in the first 30 days (13.6%). There
      was a strong graded relation between increasing NIHSS score and higher 30-day
      mortality. The 30-day mortality rates for acute ischemic stroke by NIHSS
      categories were as follows: 0 to 7, 4.2%; 8 to 13, 13.9%; 14 to 21, 31.6%; 22 to
      42, 53.5%. A model with NIHSS alone provided excellent discrimination whether
      included as a continuous variable (c-statistic 0.82 [0.81 to 0.83]), 4 categories
      (c-statistic 0.80 [0.79 to 0.80]), or 3 categories (c-statistic 0.79 [0.78 to
      0.79]). CONCLUSIONS: The NIHSS provides substantial prognostic information
      regarding 30-day mortality risk in Medicare beneficiaries with acute ischemic
      stroke. This index of stroke severity is a very strong discriminator of mortality
      risk, even in the absence of other clinical information, whether used as a
      continuous or categorical risk determinant. (J Am Heart Assoc. 2012;1:42-50.).

PMID- 23130118
TI  - Effect of aspirin versus clopidogrel on walking exercise performance in
      intermittent claudication-a double-blind randomized multicenter trial.
AB  - BACKGROUND: This study sought to determine possible effects of different
      antiplatelet therapies on walking exercise performance in intermittent
      claudication. Aspirin, in contrast to clopidogrel, interferes with processes that
      increase collateral conductance in an ischemic animal model. METHODS AND RESULTS:
      Patients with stable intermittent claudication were recruited from 21 centers in
      Switzerland and Germany and randomized to either aspirin or clopidogrel
      treatment. They participated in a 3-month rehabilitation program (electronically
      monitored, home-based, 1-hour daily walking sessions at a speed of approximately
      120 steps/min). Walking distance was assessed by treadmill tests (3.2 km/h; 12%
      grade) at baseline and after 12 weeks. A total of 229 of 259 patients with a mean
      age of 66.2+/-7.7 years completed the study according to the protocol. A total of
      24.5% were females, 20.1% diabetics, and 85.6% were active/ex-smokers. The
      baseline characteristics were a median (interquartile range) ankle/brachial index
      of 0.69 (0.57+/-0.8), an initial claudication distance (ICD) of 98 m (70 to 151
      m), and an absolute claudication distance (ACD) of 162 m (113 to 302 m). Training
      resulted in a median increase of initial claudication distance by 33.5 m (33.3%)
      in the clopidogrel group and 29 m (33.9%) in the aspirin group. The values for
      absolute claudication distance were 60.5 m (34.9%) and 75 m (35.3%), respectively
      (p(ICD)=0.42 and p(ACD)=0.66). CONCLUSIONS: Treatment with aspirin did not show a
      difference in initial claudication distance or absolute claudication distance
      improvements compared with clopidogrel after a 3-month walking rehabilitation
      program. (J Am Heart Assoc. 2012;1:51-56.) CLINICAL TRIAL REGISTRATION: URL:
      http://www.ClinicalTrials.gov. Unique identifier: NCT00189618, URL:
      https://EudraCT.ema.europa.eu, Unique identifier: 2004-005041-35.

PMID- 23130119
TI  - Diazoxide maintains human myocyte volume homeostasis during stress.
AB  - BACKGROUND: Exposure to hypothermic hyperkalemic cardioplegia, hyposmotic stress,
      or metabolic inhibition results in significant animal myocyte swelling (6% to10%)
      and subsequent reduced contractility (10% to 20%). Both are eliminated by the
      adenosine triphosphate-sensitive potassium channel opener diazoxide (DZX). The
      relationship between swelling and reduced contractility suggests that the
      structural change may represent one mechanism of postoperative myocardial
      stunning. This study evaluated human myocyte volume during stress to investigate
      if similar phenomena exist in human myocytes. METHODS AND RESULTS: Human atrial
      myocytes isolated from tissue obtained during cardiac surgery were perfused with
      Tyrode's physiological solution (20 minutes, 37 degrees C), test solution (20
      minutes), and Tyrode's (37 degrees C, 20 minutes). Test solutions (n=6 to 12
      myocytes each) included Tyrode's (37 degrees C or 9 degrees C), Tyrode's+DZX (9
      degrees C), hyperkalemic cardioplegia (9 degrees C)+/-DZX, cardioplegia+DZX+HMR
      1098 (sarcolemmal adenosine triphosphate-sensitive potassium channel inhibitor, 9
      degrees C), cardioplegia+DZX+5-hydroxydeconoate (mitochondrial adenosine
      triphosphate-sensitive potassium channel inhibitor, 9 degrees C), mild hyposmotic
      solution+/-DZX, metabolic inhibition+/-DZX, and metabolic inhibition+DZX+5
      hydroxydeconoate. Myocyte volume was recorded every 5 minutes. Exposure to
      hypothermic hyperkalemic cardioplegia, hyposmotic stress, or metabolic inhibition
      resulted in significant human myocyte swelling (8%, 7%, and 6%, respectively; all
      P<0.05 vs control). In all groups, the swelling was eliminated or lessened by
      DZX. The addition of channel inhibitors did not significantly alter results.
      CONCLUSIONS: DZX maintains human myocyte volume homeostasis during stress via an
      unknown mechanism. DZX may prove to be clinically useful following the
      elucidation of its specific mechanism of action. (J Am Heart Assoc. 2012;1:jah3
      e000778 doi: 10.1161/JAHA.112.000778.).

PMID- 23130120
TI  - Resource Utilization Reduction for Evaluation of Chest Pain in Pediatrics Using a
      Novel Standardized Clinical Assessment and Management Plan (SCAMP).
AB  - BACKGROUND: Chest pain is a common reason for referral to pediatric
      cardiologists. Although pediatric chest pain is rarely attributable to serious
      cardiac pathology, extensive and costly evaluation is often performed. We have
      implemented a standardized approach to pediatric chest pain in our pediatric
      cardiology clinics as part of a broader quality improvement initiative termed
      Standardized Clinical Assessment and Management Plans (SCAMPs). In this study, we
      evaluate the impact of a SCAMP for chest pain on practice variation and resource
      utilization. METHODS AND RESULTS: We compared demographic variables, clinical
      characteristics, and cardiac testing in a historical cohort (n=406) of patients
      presenting to our outpatient division for initial evaluation of chest pain in the
      most recent pre-SCAMP calendar year (2009) to patients enrolled in the chest pain
      SCAMP (n=364). Demographic variables including age at presentation, sex, and
      clinical characteristics were similar between groups. Adherence to the SCAMP
      algorithm for echocardiography was 84%. Practice variation decreased
      significantly after implementation of the SCAMP (P<0.001). The number of exercise
      stress tests obtained was significantly lower in the SCAMP-enrolled patients
      compared with the historic cohort (~3% of patients versus 29%, respectively;
      P<0.001). Similarly, there was a 66% decrease in utilization of Holter monitors
      and 75% decrease in the use of long-term event monitors after implementation of
      the chest pain SCAMP (P=0.003 and P<0.001, respectively). The number of
      echocardiograms obtained was similar between groups. CONCLUSIONS: Implementation
      of a SCAMP for evaluation of pediatric chest pain has lead to a decrease in
      practice variation and resource utilization. (J Am Heart Assoc. 2012;1:jah3
      e000349 doi: 10.1161/JAHA.111.000349.).

PMID- 23130121
TI  - Apolipoprotein C-III as a Potential Modulator of the Association Between HDL
      Cholesterol and Incident Coronary Heart Disease.
AB  - BACKGROUND: High-density lipoproteins (HDL) are structurally and metabolically
      heterogeneous and subclasses with differential effects on coronary heart disease
      (CHD) might exist. Apolipoprotein (apo) C-III, a small proinflammatory protein
      that resides on the surface of lipoproteins, enhances the atherogenicity of VLDL
      and LDL particles, but little is known about the role apoC-III on HDL. We
      investigated whether the presence or absence of apoC-III differentiates HDL into
      subtypes with nonprotective or protective associations with risk of future CHD.
      METHODS AND RESULTS: High-density lipoprotein cholesterol (HDL-C) levels were
      measured in plasma separated according to apoC-III (by immunoaffinity
      chromatography) in two prospective case-control studies nested within the Nurses'
      Health and the Health Professionals Follow-Up Studies. Baseline was in 1990 and
      1994, and 634 incident CHD cases were documented through 10 to 14 years of follow
      up. The relative risk of CHD per each standard deviation of total HDL-C was 0.78
      (95% confidence intervals, 0.63-0.96). The HDL-C subtypes were differentially
      associated with risk of CHD, HDL-C without apoC-III inversely and HDL-C with apoC
      III directly (P=0.02 for a difference between the HDL types). The relative risk
      per standard deviation of HDL-C without apoC-III was 0.66 (0.53 to 0.93) and 1.18
      (1.03 to 1.34) for HDL-C with apoC-III. HDL-C with apoC-III comprised ~13% of the
      total HDL-C. Adjustment for triglycerides and apoB attenuated the risks; however,
      the two HDL-C subgroups remained differentially associated with risk of CHD
      (P=0.05). CONCLUSION: Separating HDL-C according to apoC-III identified two types
      of HDL with opposing associations with risk of CHD. The proatherogenic effects of
      apoC-III, as a component of VLDL and LDL, may extend to HDL. (J Am Heart Assoc.
      2012;1:jah3-e000232 doi: 10.1161/JAHA.111.000232.).

PMID- 23130122
TI  - Carotid Intima-Media Thickness Progression in HIV-Infected Adults Occurs
      Preferentially at the Carotid Bifurcation and Is Predicted by Inflammation.
AB  - BACKGROUND: Shear stress gradients and inflammation have been causally associated
      with atherosclerosis development in carotid bifurcation regions. The mechanism
      underlying higher levels of carotid intima-media thickness observed among HIV
      infected individuals remains unknown. METHODS AND RESULTS: We measured carotid
      intima-media thickness progression and development of plaque in the common
      carotid, bifurcation region, and internal carotid artery in 300 HIV-infected
      persons and 47 controls. The median duration of follow-up was 2.4 years. When all
      segments were included, the rate of intima-media thickness progression was
      greater in HIV-infected subjects compared with controls after adjustment for
      traditional risk factors (0.055 vs. 0.024 mm/year, P=0.016). Rate of progression
      was also greater in the bifurcation region (0.067 vs. 0.025 mm/year, P=0.042)
      whereas differences were smaller in the common and internal regions. HIV-infected
      individuals had a greater incidence of plaque compared with controls in the
      internal (23% vs. 6.4%, P=0.0037) and bifurcation regions (34% vs. 17%, P=0.014).
      Among HIV-infected individuals, the rate of progression in the bifurcation region
      was more rapid compared with the common carotid, internal, or mean intima-media
      thickness; in contrast, progression rates among controls were similar at all
      sites. Baseline hsCRP was elevated in HIV-infected persons and was a predictor of
      progression in the bifurcation region. CONCLUSIONS: Atherosclerosis progresses
      preferentially in the carotid bifurcation region in HIV-infected individuals.
      hsCRP, a marker of inflammation, is elevated in HIV and is associated with
      progression in the bifurcation region. These data are consistent with a model in
      which the interplay between hemodynamic shear stresses and HIV-associated
      inflammation contribute to accelerated atherosclerosis. (J Am Heart Assoc.
      2012;1:jah3-e000422 doi: 10.1161/JAHA.111.000422.) CLINICAL TRIAL REGISTRATION:
      URL: http://clinicaltrials.gov. Unique identifier: NCT01519141.

PMID- 23130123
TI  - Biological Heart Rate Reduction Through Genetic Suppression of Galpha(s) Protein
      in the Sinoatrial Node.
AB  - BACKGROUND: Elevated heart rate represents an independent risk factor for
      cardiovascular outcome in patients with heart disease. In the sinoatrial node,
      rate increase is mediated by beta(1) adrenoceptor mediated activation of the
      Galpha(s) pathway. We hypothesized that genetic inactivation of the stimulatory
      Galpha(s) protein in the sinoatrial node would provide sinus rate control and
      would prevent inappropriate heart rate acceleration during beta-adrenergic
      activation. METHODS AND RESULTS: Domestic pigs (n=10) were evenly assigned to
      receive either Ad-small interfering RNA (siRNA)-Galpha(s) gene therapy to
      inactivate Galpha(s) or adenovirus encoding for green fluorescent protein (Ad
      GFP) as control. Adenoviruses were applied through virus injection into the
      sinoatrial node followed by epicardial electroporation, and heart rates were
      evaluated for 7 days. Genetic inhibition of Galpha(s) protein significantly
      reduced mean heart rates on day 7 by 16.5% compared with control animals (110+/
      8.8 vs 131+/-9.4 beats per minute; P<0.01). On beta-adrenergic stimulation with
      isoproterenol, we observed a tendency toward diminished rate response in the Ad
      siRNA-Galpha(s) group (Ad-siRNA-Galpha(s), +79.3%; Ad-GFP, +61.7%; n=3 animals
      per group; P= 0.294). Adverse effects of gene transfer on left ventricular
      ejection fraction (LVEF) were not detected following treatment (LVEF(Ad-siRNA
      Galphas), 66%; LVEF(Ad-GFP), 60%). CONCLUSIONS: In this preclinical proof-of
      concept study targeted Ad-siRNA-Galpha(s) gene therapy reduced heart rates during
      normal sinus rhythm compared with Ad-GFP treatment and prevented inappropriate
      rate increase after beta-adrenergic stimulation. Gene therapy may provide an
      additional therapeutic option for heart rate reduction in cardiac disease. (J Am
      Heart Assoc. 2012;1:jah3-e000372 doi: 10.1161/JAHA.111.000372).

PMID- 23130124
TI  - Tafazzin knockdown in mice leads to a developmental cardiomyopathy with early
      diastolic dysfunction preceding myocardial noncompaction.
AB  - BACKGROUND: Barth syndrome is a rare, multisystem disorder caused by mutations in
      tafazzin that lead to cardiolipin deficiency and mitochondrial abnormalities.
      Patients most commonly develop an early-onset cardiomyopathy in infancy or fetal
      life. METHODS AND RESULTS: Knockdown of tafazzin (TAZKD) in a mouse model was
      induced from the start of gestation via a doxycycline-inducible shRNA transgenic
      approach. All liveborn TAZKD mice died within the neonatal period, and in vivo
      echocardiography revealed prenatal loss of TAZKD embryos at E12.5-14.5. TAZKD
      E13.5 embryos and newborn mice demonstrated significant tafazzin knockdown, and
      mass spectrometry analysis of hearts revealed abnormal cardiolipin profiles
      typical of Barth syndrome. Electron microscopy of TAZKD hearts demonstrated
      ultrastructural abnormalities in mitochondria at both E13.5 and newborn stages.
      Newborn TAZKD mice exhibited a significant reduction in total mitochondrial area,
      smaller size of individual mitochondria, reduced cristae density, and disruption
      of the normal parallel orientation between mitochondria and sarcomeres.
      Echocardiography of E13.5 and newborn TAZKD mice showed good systolic function,
      but early diastolic dysfunction was evident from an abnormal flow pattern in the
      dorsal aorta. Strikingly, histology of E13.5 and newborn TAZKD hearts showed
      myocardial thinning, hypertrabeculation and noncompaction, and defective
      ventricular septation. Altered cellular proliferation occurring within a narrow
      developmental window accompanied the myocardial hypertrabeculation-noncompaction.
      CONCLUSIONS: In this murine model, tafazzin deficiency leads to a unique
      developmental cardiomyopathy characterized by ventricular myocardial
      hypertrabeculation-noncompaction and early lethality. A central role of
      cardiolipin and mitochondrial functioning is strongly implicated in cardiomyocyte
      differentiation and myocardial patterning required for heart development. (J Am
      Heart Assoc. 2012;1:jah3-e000455 doi: 10.1161/JAHA.111.000455.).

PMID- 23130125
TI  - Diabetes and reduced risk for thoracic aortic aneurysms and dissections: a
      nationwide case-control study.
AB  - BACKGROUND: Vascular diseases are the principal causes of death and disability in
      people with diabetes. At the same time, studies suggest a protective role of
      diabetes in the development of abdominal aortic aneurysms. We sought to determine
      whether diabetes is associated with decreased hospitalization due to thoracic
      aortic aneurysms and dissections (TAAD). METHODS AND RESULTS: We used the 2006
      and 2007 Nationwide Inpatient Sample (NIS) to determine TAAD discharge rates.
      Control subjects were randomly selected to achieve three controls per case.
      Predictor variables in multilevel logistic regression included age, race, median
      income, diabetes, and hypertension. We estimated that the average rate of
      hospital discharge for TAAD among individuals diagnosed with diabetes was 9.7 per
      10 000, compared to 15.6 per 10 000 among all discharges. The prevalence of
      diabetes was substantially lower in TAAD (13%) than in control (22%) records.
      After adjustment for demographic characteristics, the negative association
      between diabetes and TAAD remained highly significant in both NIS datasets.
      Compared to discharges without diabetes, those with chronic complications of
      diabetes were least likely to be diagnosed with TAAD (OR [odds ratio] 0.17, 95%
      CI, 0.12-0.23). A significant association remained between uncomplicated diabetes
      and TAAD. We replicated these findings in an independent group of patients who
      were hospitalized with acute thoracic aortic dissections. CONCLUSIONS: The
      principal implication of our findings is that diabetes is independently
      associated with a decreased rate of hospitalization due to TAAD in proportion to
      the severity of diabetic complications. Future studies should consider diabetes
      in predictive models of aneurysm expansion or dissection. (J Am Heart Assoc.
      2012;1:jah3-e000323 doi: 10.1161/JAHA.111.000323.).

PMID- 23130127
TI  - Cardiovascular pharmacogenomics: current status and future directions-report of a
      national heart, lung, and blood institute working group.

PMID- 23130126
TI  - Updates in cardiac amyloidosis: a review.

PMID- 23130128
TI  - Genotype- and Sex-Specific QT-RR Relationship in the Type-1 Long-QT Syndrome.
AB  - BACKGROUND: Genotype-phenotype investigations have revealed significantly larger
      risk for cardiac events in patients with type 1 long-QT syndrome (LQT-1),
      particularly in adult females, with missense mutation in the cytoplasmic loop (C
      loop) regions of the alpha subunit of the KCNQ1 gene associated with an impaired
      ion channel activation by adrenergic stimulus. We hypothesize that the impaired
      response to increases in heart rate leads to abnormal QT-RR dynamic profiles and
      is responsible for the increased cardiac risk for these patients. METHODS AND
      RESULTS: We measured the QT-RR slope in 24-hour Holter ECGs from LQT-1 patients
      with the mutations associated with impaired adrenergic stimulus (C-loop, n=18)
      and compared to LQT-1 patients with other mutations (non-C-loop, n=48), and to a
      healthy control group (n=195). The diurnal QT-RR slope was less steep in C-loop
      mutation patients (0.10+/-0.05) than in the ECGs from non-C-loop mutation
      patients (0.17+/-0.09, P=0.002). For female patients, slower heart rates were
      associated with prolonged QT and increased QT-RR slope. Male patients with C-loop
      mutations showed an impaired repolarization for shorter range of heart rates than
      in females, which is consistent with gender differences in triggers for events in
      this syndrome. CONCLUSIONS: Our observations suggest that the C-loop LQT-1
      patients have specific impaired adrenergic regulation of the ventricular
      repolarization. This response to heart rate increases may be useful in
      identification of high-risk patients with inherited prolonged QT and may help
      select an optimal antiarrhythmic therapeutic strategy. (J Am Heart Assoc.
      2012;1:e000570 doi: 10.1161/JAHA.112.000570.).

PMID- 23130129
TI  - Carotid Artery Imaging: Insights Into Inflammation and Cardiovascular Disease
      Risk in Patients With HIV Infection.

PMID- 23130130
TI  - Genetic silencing of pacemaker cells: local intervention with global
      implications.

PMID- 23130131
TI  - Myocardial Revascularization in New York State: Variations in the PCI-to-CABG
      Ratio and Their Implications.
AB  - BACKGROUND: During the past 2 decades, percutaneous coronary intervention (PCI)
      has increased dramatically compared with coronary artery bypass grafting (CABG)
      for patients with coronary artery disease. However, although the evidence
      available to all practitioners is similar, the relative distribution of PCI and
      CABG appears to differ among hospitals and regions. METHODS AND RESULTS: We
      reviewed the published data from the mandatory New York State Department of
      Health annual cardiac procedure reports issued from 1994 through 2008 to define
      trends in PCI and CABG utilization in New York and to compare the PCI/CABG ratios
      in the metropolitan area to the remainder of the State. During this 15-year
      interval, the procedure volume changes for CABG, for all cardiac surgeries, for
      non-CABG cardiac surgeries, and for PCI for New York State were -40%, -20%,
      +17.5%, and +253%, respectively; for the Manhattan programs, the changes were
      similar as follows: -61%, -23%, +14%, and +284%. The average PCI/CABG ratio in
      New York State increased from 1.12 in 1994 to 5.14 in 2008; however, in
      Manhattan, the average PCI/CABG ratio increased from 1.19 to 8.04 (2008 range:
      3.78 to 16.2). The 2008 PCI/CABG ratios of the Manhattan programs were higher
      than the ratios for New York City programs outside Manhattan, in Long Island, in
      the northern counties contiguous to New York City, and in the rest of New York
      State; their averages were 5.84, 5.38, 3.31, and 3.24, respectively. In
      Manhattan, a patient had a 56% greater chance of receiving PCI than CABG as
      compared with the rest of New York State; in one Manhattan program, the
      likelihood was 215% higher. CONCLUSIONS: There are substantial regional and
      statewide differences in the utilization of PCI versus CABG among cardiac centers
      in New York, possibly related to patient characteristics, physician biases, and
      hospital culture. Understanding these disparities may facilitate the selection of
      the most appropriate, effective, and evidence-based revascularization strategy.
      (J Am Heart Assoc. 2012;1:e001446 doi: 10.1161/JAHA.112.001446.).

PMID- 23130132
TI  - Arrhythmias after heart transplantation: mechanisms and management.

PMID- 23130133
TI  - Two decades of endovascular abdominal aortic aneurysm repair: enormous progress
      with serious lessons learned.

PMID- 23130134
TI  - A Randomized, Placebo-Controlled Trial of Omega-3 Fatty Acids for Inhibition of
      Supraventricular Arrhythmias After Cardiac Surgery: The FISH Trial.
AB  - BACKGROUND: Omega-3 polyunsaturated fatty acids (n3-PUFAs) might have
      antiarrhythmic properties, but data conflict on whether n3-PUFAs reduce rates of
      atrial fibrillation (AF) after coronary artery bypass graft surgery (CABG). We
      hypothesized that n3-PUFAs would reduce post-CABG AF, and we tested this
      hypothesis in a well-powered, randomized, double-blind, placebo-controlled,
      multicenter clinical trial. METHODS AND RESULTS: Patients undergoing CABG were
      randomized to pharmaceutical-grade n3-PUFAs 2 g orally twice daily (minimum of 6
      g) or a matched placebo >=24 hours before surgery. Gas chromatography was used to
      assess plasma fatty acid composition of samples collected on the day of
      screening, day of surgery, and postoperative day 4. Treatment continued either
      until the primary end point, clinically significant AF requiring treatment,
      occurred or for a maximum of 2 weeks after surgery. Two hundred sixty patients
      were enrolled and randomized. Before surgery, n3-PUFA dosing increased plasma n3
      PUFA levels from 2.9% to 4% and reduced the n6:n3-PUFA ratio from 9.1 to 6.4
      (both P<0.001). Similar changes were noted on postoperative day 4. There were no
      lipid changes in the placebo group. The rate of post-CABG AF was similar in both
      groups (30% n3-PUFAs versus 33% placebo, P=0.67). The post-CABG AF odds ratio for
      n3-PUFAs relative to placebo was 0.89 (95% confidence interval 0.52-1.53). There
      were no differences in any secondary end points. CONCLUSIONS: Oral n3-PUFA
      supplementation begun 2 days before CABG did not reduce AF or other complications
      after surgery. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov
      Unique identifier: NCT00446966. (J Am Heart Assoc. 2012;1:e000547 doi:
      10.1161/JAHA.111.000547.).

PMID- 23130135
TI  - High On-Aspirin Platelet Reactivity and Clinical Outcome in Patients With Stable
      Coronary Artery Disease: Results From ASCET (Aspirin Nonresponsiveness and
      Clopidogrel Endpoint Trial).
AB  - BACKGROUND: Patients with stable coronary artery disease on single-antiplatelet
      therapy with aspirin are still at risk for atherothrombotic events, and high on
      aspirin residual platelet reactivity (RPR) has been suggested as a risk factor.
      METHODS AND RESULTS: In this randomized trial, the association between platelet
      function determined by the PFA100 platelet function analyzer system (Siemens
      Healthcare Diagnostics, Germany) and clinical outcome in 1001 patients, all on
      single-antiplatelet therapy with aspirin (160 mg/d) was studied. Patients were
      randomized to continue with aspirin 160 mg/d or change to clopidogrel 75 mg/d. A
      composite end point of death, myocardial infarction, ischemic stroke, and
      unstable angina was used. At 2-year follow-up, 106 primary end points were
      registered. The prevalence of high RPR was 25.9%. High on-aspirin RPR did not
      significantly influence the primary end point in the aspirin group (13.3% versus
      9.9%, P=0.31). However, in post hoc analysis, patients with von Willebrand factor
      levels or platelet count below median values and high on-aspirin RPR had a
      statistically significant higher end point rate than that of patients with low
      RPR (20% versus 7.5%, P=0.014, and 18.2% versus 10.8%, P=0.039, respectively).
      The composite end point rate in patients with high on-aspirin RPR treated with
      clopidogrel was not different from that of patients treated with aspirin (7.6%
      versus 13.3%, P=0.16). CONCLUSIONS: In stable, aspirin-treated patients with
      coronary artery disease, high on-aspirin RPR did not relate to clinical outcome
      and did not identify a group responsive to clopidogrel. Post hoc subgroup
      analysis raised the possibility that high on-aspirin RPR might be predictive in
      patients with low von Willebrand factor or platelet count, but these findings
      will require confirmation in future studies. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov Unique identifier: NCT00222261. (J Am Heart Assoc.
      2012;1:e000703 doi: 10.1161/JAHA.112.000703.).

PMID- 23130136
TI  - The oxysterol 24(s),25-epoxycholesterol attenuates human smooth muscle-derived
      foam cell formation via reduced low-density lipoprotein uptake and enhanced
      cholesterol efflux.
AB  - BACKGROUND: Foam cell formation by intimal smooth muscle cells (SMCs) inhibits
      the elaboration of extracellular matrix, which is detrimental to plaque
      stabilization. In the present study, we examined the lipoproteins and receptors
      involved in human SMC foam cell formation and investigated the ability of
      24(S),25-epoxycholesterol [24(S),25-EC], an oxysterol agonist of the liver X
      receptor, to attenuate SMC foam cell formation. METHODS AND RESULTS: Incubation
      of human internal thoracic SMCs with atherogenic lipoproteins demonstrated that
      low-density lipoprotein (LDL), but not oxidized or acetylated LDL, was the
      primary lipoprotein taken up, resulting in marked cholesteryl ester deposition (6
      fold vs 1.8-fold; P<0.05; n=4). Exposure of SMCs to exogenous or endogenously
      synthesized 24(S),25-EC attenuated LDL uptake (-90% and -47% respectively;
      P<0.05; n=3) through decreased sterol regulatory element-binding protein-2
      expression (-30% and -17%, respectively; P<0.001; n=3), decreased LDL receptor
      expression (-75% and -40%, respectively; P<0.05; n=3) and increased liver X
      receptor-mediated myosin regulatory light chain interacting protein expression (7
      and 3-fold, respectively; P<0.05; n=4). Furthermore, exogenous 24(S),25-EC
      increased adenosine triphosphate-binding cassettes A1- and G1-mediated
      cholesterol efflux to apolipoprotein AI (1.9-fold; P<0.001; n=5) and high-density
      lipoprotein(3) (1.3-fold; P<0.05; n=5). 24(S),25-EC, unlike a nonsteroidal liver
      X receptor agonist, T0901317, did not stimulate sterol regulatory element-binding
      protein-1c-mediated fatty acid synthesis or triglyceride accumulation. 24(S),25
      EC preserved the assembly of fibronectin and type I collagen by SMCs.
      CONCLUSIONS: The oxysterol 24(S),25-EC prevented foam cell formation in human
      SMCs by attenuation of LDL receptor-mediated LDL uptake and stimulation of
      cholesterol efflux, restoring the elaboration of extracellular matrix. In
      contrast to T0901317, 24(S),25-EC prevented the development of a triglyceride
      rich foam cell phenotype. (J Am Heart Assoc. 2012;1:e000810 doi:
      10.1161/JAHA.112.000810.).

PMID- 23130137
TI  - Histone deacetylase activity selectively regulates notch-mediated smooth muscle
      differentiation in human vascular cells.
AB  - BACKGROUND: Histone deacetylases (HDACs) modify smooth muscle cell (SMC)
      proliferation and affect neointimal lesion formation by regulating cell cycle
      progression. HDACs might also regulate SMC differentiation, although this is not
      as well characterized. METHODS AND RESULTS: Notch signaling activates SMC
      contractile markers and the differentiated phenotype in human aortic SMCs. Using
      this model, we found that HDAC inhibition antagonized the ability of Notch to
      increase levels of smooth muscle alpha-actin, calponin1, smooth muscle 22alpha,
      and smooth muscle myosin heavy chain. However, inhibition of HDAC activity did
      not suppress Notch activation of the HRT target genes. In fact, HDAC inhibition
      increased activation of the canonical C-promoter binding factor-1 (CBF-1)
      mediated Notch pathway, which activates HRT transcription. Although CBF-1
      mediated Notch signaling was increased by HDAC inhibition in human SMCs and in a
      C3H10T1/2 model, SMC differentiation was inhibited in both cases. Further
      characterization of downstream Notch signaling pathways showed activation of the
      c-Jun N-terminal kinase, p38 mitogen-activated protein kinase, and PI3K/Akt
      pathways. The activation of these pathways was sensitive to HDAC inhibition and
      was positively correlated with the differentiated phenotype. CONCLUSIONS: Our
      studies define novel signaling pathways downstream of Notch signaling in human
      SMCs. In addition to the canonical CBF-1 pathway, Notch stimulates c-Jun N
      terminal kinase, mitogen-activated protein kinase, and PI3K cascades. Both
      canonical and noncanonical pathways downstream of Notch promote a differentiated,
      contractile phenotype in SMCs. Although CBF-1-mediated Notch signaling is not
      suppressed by HDAC inhibition, HDAC activity is required for Notch
      differentiation signals through mitogen-activated protein kinase and PI3K
      pathways in SMCs. (J Am Heart Assoc. 2012;1:e000901 doi:
      10.1161/JAHA.112.000901).

PMID- 23130138
TI  - Global Psychological Distress and Risk of Atrial Fibrillation Among Women: The
      Women's Health Study.
AB  - BACKGROUND: Symptoms of psychological distress and depression have been
      associated with risk of ventricular arrhythmias and sudden cardiac death. Their
      relationship with atrial arrhythmias, however, is less well studied. METHODS AND
      RESULTS: We sought to assess the long-term relations between psychological
      distress and risk of atrial fibrillation (AF) in the Women's Health Study of
      female health professionals. We measured psychological symptoms with the Mental
      Health Inventory-5. Incident AF was assessed annually and verified through
      medical records. Among 30 746 women without history of cardiovascular disease or
      AF, 771 cases of AF occurred during a median follow-up of 125 months
      (interquartile range, 117-130 months). Global psychological distress was not
      associated with AF risk in age-stratified (P=0.61 for linear trend) or
      multivariable proportional-hazards models that included antidepressant use
      (P=0.34). A proxy measure for depression, consisting of Mental Health Inventory-5
      score <53, antidepressant use, or both, was also not associated with AF risk in
      multivariable models (hazard ratio=0.99; 95% confidence interval, 0.78-1.25;
      P=0.93). In post hoc analyses of individual symptoms from the Mental Health
      Inventory-5, positive affect, "feeling happy some/a good bit of the time," was
      associated with reduced risk of AF (hazard ratio=0.69; 95% confidence interval,
      0.49-0.99; P=0.04); other depressive and anxious symptoms were not. CONCLUSIONS:
      In this prospective study of women without known cardiovascular disease, global
      psychological distress and specific depressive symptoms were unrelated to AF
      risk. (J Am Heart Assoc. 2012;1:e001107 doi: 10.1161/JAHA.112.001107.).

PMID- 23130140
TI  - Diabetes mellitus and thoracic aortic disease: are people with diabetes mellitus
      protected from acute aortic dissection?

PMID- 23130139
TI  - High level of plasma estradiol as a new predictor of ischemic arterial disease in
      older postmenopausal women: the three-city cohort study.
AB  - BACKGROUND: Despite evidence that estrogens may be involved in atherothrombosis,
      the role of endogenous sex steroid hormones in ischemic arterial disease among
      postmenopausal women remains uncertain. METHODS AND RESULTS: In the Three-City
      prospective cohort study of subjects (n=9294) >65 years of age, we investigated
      the association of total 17beta-estradiol, bioavailable 17beta-estradiol, and
      total testosterone with the 4-year incidence of ischemic arterial disease among
      postmenopausal women who did not use any hormone therapy. We designed a case
      cohort study including a random sample of 537 subjects and 106 incident cases of
      first cardiovascular events. Weighted Cox proportional-hazards models with age as
      the time scale were used to estimate hazard ratios (HRs) and corresponding 95%
      confidence intervals (CIs) for ischemic arterial disease by a 1-standard
      deviation increase in sex steroid hormones. In univariate analysis, HR of
      ischemic arterial disease was positively and significantly associated with both
      total and bioavailable estradiol levels. These associations remained significant
      after adjustment for traditional cardiovascular risk factors, including body mass
      index, diabetes, hypercholesterolemia, hypertension, and smoking status (HR:
      1.42, 95% CI: 1.12-1.79, P<0.01; and HR: 1.42, 95% CI: 1.12-1.78, P<0.01,
      respectively). Separate analysis for coronary heart disease yielded similar
      results (adjusted HR: 1.49, 95% CI: 1.10-2.02, P=0.01; and adjusted HR: 1.50, 95%
      CI: 1.11-2.04, P<0.01, respectively), and a borderline significant trend was
      observed for ischemic stroke (HR: 1.34, 95% CI: 0.95-1.89, P=0.08; and HR: 1.32,
      95% CI: 0.94-1.84, P=0.11, respectively). By contrast, no significant association
      was found between total testosterone and ischemic arterial disease in both
      univariate and adjusted analyses. CONCLUSIONS: High plasma level of endogenous
      estradiol emerges as a new predictor of ischemic arterial disease in older
      postmenopausal women. (J Am Heart Assoc. 2012;1:e001388 doi:
      10.1161/JAHA.112.001388.).

PMID- 23130141
TI  - Vulnerable myocardial interstitium in patients with isolated left ventricular
      hypertrophy and sudden cardiac death: a postmortem histological evaluation.
AB  - BACKGROUND: Concentric left ventricular hypertrophy (LVH) is independently
      associated with increased risk of sudden cardiac death (SCD). Some animal models
      of LVH display specific alterations of the myocardial interstitium that could
      increase myocardial vulnerability to ventricular arrhythmias, but these merit
      evaluation in humans with LVH and SCD. METHODS AND RESULTS: Twelve consecutive
      patients with isolated LVH and SCD (LVH+SCD) in the absence of hypertrophic
      cardiomyopathy, coronary disease, or other cardiac structural abnormality were
      ascertained in the Oregon Sudden Unexpected Death Study. Detailed postmortem
      comparisons were conducted with 18 controls who had isolated LVH and unnatural
      deaths (Control Group A) and 6 controls who had structurally normal hearts and
      unnatural deaths (Control Group B). Postmortem left ventricular myocardial
      sections were obtained for measurement of collagen volume fraction,
      characterization of gap junctions, and quantification of collagen subtypes. Heart
      weight normalized to body weight was higher in LVH+SCD cases (6.9+/-1.2 g/kg)
      than in Control Group A (5.3+/-1.4 g/kg) and Control Group B (4.2+/-0.3 g/kg);
      P=0.001. Collagen volume fraction was also higher in LVH+SCD cases (3.1+/-0.4)
      than in Control Group A (2.3+/-0.4) and Control Group B (1.6+/-0.3); P=0.0002.
      The relative amount of collagen III was significantly higher in LVH+SCD cases
      (33.0+/-4.4%) than in Control Group A (20.9+/-4.3%) and Control Group B (13.4+/
      3.5%); P=0.0001. There was an overall increase in the number of connexin 43
      labeled gap junctions with increasing myocyte size. No subject was found to have
      high-risk hypertrophic cardiomyopathy mutations. CONCLUSIONS: In addition to the
      expected increase in myocardial mass and overall collagen content, SCD with
      isolated LVH was associated with relative abundance of type III collagen, a novel
      finding that warrants further mechanistic evaluation. (J Am Heart Assoc.
      2012;1:e001511 doi: 10.1161/JAHA.111.001511.).

PMID- 23130142
TI  - Risk of idiopathic dilated cardiomyopathy in 29 000 patients with celiac disease.
AB  - BACKGROUND: Dilated cardiomyopathy (DCM) is a rare disease of largely unknown
      origin. Previous studies have suggested an increased prevalence of celiac disease
      (CD) in patients with DCM. These studies, however, were based on a maximum of 5
      patients with both CD and DCM. In the present large Swedish population-based
      cohort study, we examined the risk of idiopathic DCM in patients with CD
      determined by small-intestinal histopathology. METHODS AND RESULTS: From 2006 to
      2008, we collected duodenal/jejunal biopsy data on CD (equal to villous atrophy,
      Marsh stage 3, n=29 071 unique individuals) from (all) 28 pathology departments
      in Sweden. These individuals were compared with 144 429 reference individuals
      matched for age, sex, calendar year, and county. Data on DCM were obtained
      through the National Patient Register and confirmed by patient charts and
      echocardiography data. During follow-up, 17 patients with CD and 52 reference
      individuals developed idiopathic DCM. Thus, patients with CD were at an increased
      risk of idiopathic DCM (hazard ratio, 1.73; 95% confidence interval, 1.00 to
      3.00), although the risk estimate failed to attain statistical significance
      (P=0.052). CONCLUSION: This nationwide study found a moderately but not
      statistically significantly increased risk of idiopathic DCM in patients with
      biopsy-verified CD. (J Am Heart Assoc. 2012;1:e001594 doi:
      10.1161/JAHA.112.001594.).

PMID- 23130143
TI  - Reduction of ischemia/reperfusion injury with bendavia, a mitochondria-targeting
      cytoprotective Peptide.
AB  - BACKGROUND: Manifestations of reperfusion injury include myocyte death leading to
      infarction, contractile dysfunction, and vascular injury characterized by the "no
      reflow" phenomenon. Mitochondria-produced reactive oxygen species are believed to
      be centrally involved in each of these aspects of reperfusion injury, although
      currently no therapies reduce reperfusion injury by targeting mitochondria
      specifically. METHODS AND RESULTS: We investigated the cardioprotective effects
      of a mitochondria-targeted peptide, Bendavia (Stealth Peptides), across a
      spectrum of experimental cardiac ischemia/reperfusion models. Postischemic
      administration of Bendavia reduced infarct size in an in vivo sheep model by 15%
      (P=0.02) and in an ex vivo guinea pig model by 38% to 42% (P<0.05). In an in vivo
      rabbit model, the extent of coronary no-reflow was assessed with Thioflavin S
      staining and was significantly smaller in the Bendavia group for any given
      ischemic risk area than in the control group (P=0.0085). Myocardial uptake of
      Bendavia was ~25% per minute, and uptake remained consistent throughout
      reperfusion. Postischemic recovery of cardiac hemodynamics was not influenced by
      Bendavia in any of the models studied. Isolated myocytes exposed to
      hypoxia/reoxygenation showed improved survival when treated with Bendavia. This
      protection appeared to be mediated by lowered reactive oxygen species-mediated
      cell death during reoxygenation, associated with sustainment of mitochondrial
      membrane potential in Bendavia-treated myocytes. CONCLUSIONS: Postischemic
      administration of Bendavia protected against reperfusion injury in several
      distinct models of injury. These data suggest that Bendavia is a mitochondria
      targeted therapy that reduces reperfusion injury by maintaining mitochondrial
      energetics and suppressing cellular reactive oxygen species levels. (J Am Heart
      Assoc. 2012;1:e001644 doi: 10.1161/JAHA.112.001644.).

PMID- 23130144
TI  - Delay in presentation after an acute stroke in a multiethnic population in South
      london: the South london stroke register.
AB  - BACKGROUND: Delayed presentation to hospital after an acute stroke is a major
      explanation given for low thrombolysis rates. This study aimed to investigate the
      factors associated with delays in presentation after an acute stroke and changes
      after a mass media campaign. METHODS AND RESULTS: Data were from a population
      based study involving 1392 patients with first-ever strokes between 2002 and 2010
      in a multiethnic South London population. Associations were determined between
      prehospital delay (>=3 hours) and variables of interest, including ethnicity, by
      using multivariate logistic regression analyses. Differences in prehospital delay
      and thrombolysis rates were determined for the period immediately before and
      after the FAST mass media campaign (2007/2008 versus 2009/2010). The median (Q(1)
      to Q(3)) time to presentation was 4.73 (1.55 to 12.70) hours, and 550 (39.5%)
      presented within 3 hours of symptom onset. In multivariate analysis, patients of
      black ethnicity had increased odds of delay (odds ratio: 1.63; 95% confidence
      interval, 1.11 to 2.38), whereas those with more severe strokes characterized by
      a higher National Institutes of Health Stroke Scale score (odds ratio: 0.35; 95%
      confidence interval, 0.20 to 0.61) had reduced odds of delay. There was no
      difference in the proportion of patients who arrived within 3 hours (P=0.30) in
      the period immediately before and after the FAST campaign (40.7% in 2007/2008
      versus 44.9% in 2009/2010). Among patients with ischemic stroke, 119 (11.0%)
      received thrombolysis between 2002 and 2010, with no difference observed between
      the pre- and postcampaign periods (16.9% versus 16.4%). CONCLUSION: Significant
      delays in seeking care after stroke still occur in this population despite
      efforts to increase public awareness. Future educational programs must identify
      and specifically address factors that influence behavior and should target those
      at higher risk of delay. (J Am Heart Assoc. 2012;1:e001685 doi:
      10.1161/JAHA.112.001685.).

PMID- 23130145
TI  - Microparticles induce cell cycle arrest through redox-sensitive processes in
      endothelial cells: implications in vascular senescence.
AB  - BACKGROUND: Chronic disease accelerates endothelial dysfunction in aging, a
      process associated with cell senescence. However, the mechanisms underlying this
      process are unclear. We examined whether endothelial cell (EC)-derived
      microparticles (MPs) facilitate EC senescence and questioned the role of reactive
      oxygen species in this process. METHODS AND RESULTS: Senescence was induced by
      sequential passaging of primary mouse ECs. Cells retained phenotypic
      characteristics of ECs from passage 4 through passage 21. Passage 21 ECs
      exhibited features of senescence, including increased staining of senescence
      associated beta-galactosidase (SA-betagal), a greater percentage of cells in
      G(1)/G(0) phase of the cell cycle, and increased phosphorylation of p66(Shc)
      (P<0.05). Microparticle formation from passage 21 ECs was increased versus
      passage 4 ECs (~2.2-fold increase versus passage 4, P<0.05), and the Rho kinase
      inhibitor fasudil blocked this increase. Exposure of passage 4 ECs to MPs shifted
      cells from a proliferating to a nonproliferating phenotype, as indicated by cell
      cycle analysis and increased senescence-associated beta-galactosidase staining.
      MPs increased EC generation of O(2) (*-) (~2.7-fold) and H(2)O(2) (~2.6-fold),
      effects blocked by apocynin (nicotinamide adenine dinucleotide phosphate oxidase
      inhibitor) and rotenone (mitochondrial oxidase inhibitor) but not by allopurinol
      (xanthine oxidase inhibitor). MPs increased expression of cell cycle proteins p
      21 cip1 and p16ink4a and stimulated phosphorylation of p66(Shc) in ECs (P<0.05
      versus untreated ECs). Pretreatment with the reactive oxygen species scavenger
      sodium 4,5-dihydroxybenzene-1,3-disulfonate (tiron) abrogated the prosenescent
      effects of MPs. CONCLUSIONS: MPs promote EC senescence through nicotinamide
      adenine dinucleotide phosphate oxidase- and mitochondrial-derived reactive oxygen
      species. Such redox-sensitive processes may be important in vascular dysfunction
      in aging. (J Am Heart Assoc. 2012;1:e001842 doi: 10.1161/JAHA.112.001842.).

PMID- 23130146
TI  - A simple new visualization of exercise data discloses pathophysiology and
      severity of heart failure.
AB  - BACKGROUND: The complexity of cardiopulmonary exercise testing data and their
      displays tends to make assessment of patients, including those with heart
      failure, time consuming. METHODS AND RESULTS: We postulated that a new single
      display that uses concurrent values of oxygen uptake / ventilation versus carbon
      dioxide output / ventilation ratios ([Formula: see text]-versus-[Formula: see
      text]), plotted on equal X-Y axes, would better quantify normality and heart
      failure severity and would clarify pathophysiology. Consecutive [Formula: see
      text]-versus-[Formula: see text] values from rest to recovery were displayed on X
      Y axes for patients with Class II and IV heart failure and for healthy subjects
      without heart failure. The displays revealed distinctive patterns for each group,
      reflecting sequential changes in cardiac output, arterial and mixed venous O(2)
      and CO(2) content differences, and ventilation ([Formula: see text]). On the
      basis of exercise tests of 417 healthy subjects, reference formulas for highest
      [Formula: see text] and [Formula: see text], which normally occur during moderate
      exercise, are presented. Absolute and percent predicted values of highest
      [Formula: see text] and [Formula: see text] were recorded for 10 individuals from
      each group: Those of healthy subjects were significantly higher than those of
      patients with Class II heart failure, and those of patients with Class II heart
      failure were higher than those of patients with Class IV heart failure. These
      values differentiated heart failure severity better than peak [Formula: see
      text], anaerobic threshold, peak oxygen pulse, and [Formula: see text] slopes.
      Resting [Formula: see text]-versus-[Formula: see text] values were strikingly low
      for patients with Class IV heart failure, and with exercise, increased minimally
      or even decreased. With regard to the pathophysiology of heart failure, high
      [Formula: see text] values during milder exercise, previously attributed to
      ventilatory inefficiency, seem to be caused primarily by reduced cardiac output
      rather than increased [Formula: see text]. CONCLUSION: [Formula: see text]-versus
      [Formula: see text] measurements and displays, extractable from future or
      existing exercise data, separate the 3 groups (healthy subjects, patients with
      Class II heart failure, and patients with Class IV heart failure) well and
      confirm the dominant role of low cardiac output rather than excessive [Formula:
      see text] in heart failure pathophysiology. (J Am Heart Assoc. 2012;1:e001883
      doi: 10.1161/JAHA.112.001883.).

PMID- 23130147
TI  - Interleukin-1 mediates neuroinflammatory changes associated with diet-induced
      atherosclerosis.
AB  - BACKGROUND: Systemic inflammation contributes to brain pathology in
      cerebrovascular disease through mechanisms that are poorly understood. METHODS
      AND RESULTS: Here we show that atherosclerosis, a major systemic inflammatory
      disease, is associated with severe cerebrovascular inflammation in mice and that
      this effect is mediated by the proinflammatory cytokine interleukin-1 (IL-1).
      Apolipoprotein E-deficient mice fed Paigen or Western diets develop vascular
      inflammation, microglial activation, and leukocyte recruitment in the brain,
      which are absent in apolipoprotein E-deficient mice crossed with IL-1 type 1
      receptor-deficient mice. Systemic neutralization of IL-1beta with an anti-IL
      1beta antibody reversed aortic plaque formation (by 34% after a Paigen and 45%
      after a Western diet) and reduced inflammatory cytokine expression in peripheral
      organs. Central, lipid accumulation-associated leukocyte infiltration into the
      choroid plexus was reversed by IL-1beta antibody administration. Animals fed a
      Western diet showed 57% lower vascular inflammation in the brain than that of
      mice fed a Paigen diet, and this was reduced further by 24% after IL-1beta
      antibody administration. CONCLUSIONS: These results indicate that IL-1 is a key
      driver of systemically mediated cerebrovascular inflammation and that
      interventions against IL-1beta could be therapeutically useful in
      atherosclerosis, dementia, or stroke. (J Am Heart Assoc. 2012;1:e002006 doi:
      10.1161/JAHA.112.002006.).

PMID- 23130149
TI  - Put on a Happy Face-It's a Lot Better Than Coumadin.

PMID- 23130150
TI  - Reducing the delay between stroke onset and hospital arrival: is it an achievable
      goal?

PMID- 23130148
TI  - Molecular mechanisms of experimental salt-sensitive hypertension.

PMID- 23130151
TI  - FISHing for Answers in Postoperative Atrial Fibrillation.

PMID- 23130153
TI  - Quality improvement in coronary care: analysis of sustainability and impact on
      adjacent clinical measures after a Swedish controlled, multicenter quality
      improvement collaborative.
AB  - BACKGROUND: Quality Improvement in Coronary Care, a Swedish multicenter,
      controlled quality-improvement (QI) collaborative, has shown significant
      improvements in adherence to national guidelines for acute myocardial infarction,
      as well as improved clinical outcome. The objectives of this report were to
      describe the sustainability of the improvements after withdrawal of study support
      and a consolidation period of 3 months and to report whether improvements were
      disseminated to treatments and diagnostic procedures other than those primarily
      targeted. METHODS AND RESULTS: Multidisciplinary teams from 19 Swedish hospitals
      were educated in basic QI methodologies. Another 19 matched hospitals were
      included as blinded controls. All evaluations were made on the hospital level,
      and data were obtained from a national quality registry, Swedish Register of
      Information and Knowledge About Swedish Heart Intensive Care Admissions (RIKS
      HIA). Sustainability indicators consisted of use of angiotensin-converting enzyme
      inhibitors, lipid-lowering therapy, clopidogrel, low-molecular weight heparin,
      and coronary angiography. Dissemination indicators were use of echocardiography,
      stress tests, and reperfusion therapy; time delays; and length of stay. At the
      reevaluation period of 6 months, the improvements at the QI intervention
      hospitals were sustained in all indicators but 1 (angiotensin-converting enzyme
      inhibitor). Between the 2 measurements, the control group improved significantly
      in all but 1 indicator (angiotensin-converting enzyme inhibitor). However, at the
      second measurement, the absolute adherence rates of the intervention hospitals
      were still numerically higher in all 5 indicators, and significantly so in 1
      (clopidogrel). No significant changes were observed for the dissemination
      indicators. CONCLUSIONS: The combination of a systematic QI collaborative with a
      national, interactive quality registry might lead to substantial and sustained
      improvements in the quality of acute myocardial infarction care. However, to
      achieve disseminated improvements in adjacent clinical measures, those adjacent
      measures probably should be made explicit before any QI intervention. (J Am Heart
      Assoc. 2012;1:e000737 doi: 10.1161/JAHA.112.000737.).

PMID- 23130152
TI  - Cerebrovascular consequences of obstructive sleep apnea.

PMID- 23130154
TI  - Reduction of Long-Term Care Dependence After an 8-Year Primary Care Prevention
      Program for Stroke and Dementia: The INVADE Trial.
AB  - BACKGROUND: Stroke and dementia are the major causes for long-term care (LTC)
      dependence in old age. This intervention trial compared a multidomain prevention
      program for stroke and dementia with usual medical care in reducing the need for
      LTC. METHODS AND RESULTS: The Intervention Project on Cerebrovascular Disease and
      Dementia in the District of Ebersberg (INVADE) was a general practice-based 8
      year trial in 2 defined catchment areas in Upper Bavaria, Germany. All 11 317
      insurants of a statutory health insurance plan who were >=55 years of age and
      lived in the intervention district were offered the opportunity to participate in
      a prevention program; 3908 enrolled. The 13 301 insurants in the reference
      district received usual medical care. The intervention consisted of the
      systematic identification and evidence-based treatment of vascular risk factors.
      The primary clinical end point was incidence of LTC dependence according to
      external assessment by a special medical service in the framework of the
      statutory German LTC insurance. Age- and sex-specific incidence rates from the
      reference district were used to calculate the expected number of cases of LTC
      dependence under usual medical care. The expected number was compared with the
      observed number of cases in the intervention district. Analysis was by intention
      to treat. During the 5 years after completion of the recruitment period,
      significantly fewer incident cases of LTC dependence arose in the intervention
      district than expected (chi(2)=13.25; P<0.001). In women, the incidence was
      reduced by 10% (P<0.01). In men, the incidence was reduced by 9.6% (P<0.05).
      CONCLUSIONS: Our results support the feasibility and effectiveness of a primary
      care prevention program for stroke and dementia to reduce the risk of developing
      LTC dependence. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov.
      Unique identifier: NCT01107548. (J Am Heart Assoc. 2012;1:e000786 doi:
      10.1161/JAHA.112.000786.).

PMID- 23130155
TI  - Addition of inflammatory biomarkers did not improve diabetes prediction in the
      community: the framingham heart study.
AB  - BACKGROUND: Prior studies have reported conflicting findings with regard to the
      association of biomarkers in the prediction of incident type 2 diabetes. We
      evaluated 12 biomarkers as possible diabetes predictors in the Framingham Heart
      Study. METHODS AND RESULTS: Biomarkers representing inflammation (C-reactive
      protein, interleukin-6, monocyte chemoattractant protein-1, tumor necrosis factor
      receptor 2, osteoprotegerin, and fibrinogen), endothelial dysfunction
      (intercellular adhesion molecule-1), vascular damage (CD40-ligand, P-selectin,
      and lipoprotein-associated phospholipase A2 mass and activity), and oxidative
      stress (urinary isoprostanes) were measured in participants without diabetes
      attending the Offspring seventh (n=2499) or multiethnic Omni second (n=189)
      examination (1998-2001). Biomarkers were log(e) transformed and standardized.
      Multivariable logistic regression tested each biomarker in association with
      incident diabetes at a follow-up examination (the Offspring eighth and Omni third
      examination; mean 6.6 years later), with adjustment for age, sex, cohort, body
      mass index, fasting glucose, systolic blood pressure, high-density lipoprotein
      cholesterol, triglycerides, and smoking. C statistics were evaluated with and
      without inflammatory markers. In 2638 participants (56% women, mean age 59
      years), 162 (6.1%) developed type 2 diabetes. All biomarkers, excluding
      osteoprotegerin, were associated with the outcome with adjustment for age, sex,
      and cohort; however, none remained significant after multivariable adjustment
      (all P>0.05). The c statistic from the model including only clinical covariates
      (0.89) did not statistically significantly improve after addition of biomarkers
      (all P>0.10). CONCLUSIONS: Biomarkers representing different inflammatory
      pathways are associated with incident diabetes but do not remain statistically
      significant after adjustment for established clinical covariates. Inflammatory
      biomarkers might not be an effective resource to predict type 2 diabetes in
      community-based samples. (J Am Heart Assoc. 2012;1:e000737 doi:
      10.1161/JAHA.112.000869.).

PMID- 23130156
TI  - Therapeutic lymphangiogenesis with implantation of adipose-derived regenerative
      cells.
AB  - BACKGROUND: Lymphedema is one of the serious clinical problems that can occur
      after surgical resection of malignant tumors such as breast cancer or intra
      pelvic cancers. However, no effective treatment options exist at present. Here,
      we report that implantation of adipose-derived regenerative cells (ADRCs) can
      induce lymphangiogenesis in a mouse model of reparative lymphedema. METHODS AND
      RESULTS: ADRCs were isolated from C57BL/6J mice. To examine the therapeutic
      efficacy of ADRC implantation in vivo, we established a new mouse model of tail
      lymphedema. Lymphedema was improved significantly by local injection of ADRCs
      (P<0.05). Histological analysis revealed that lymphatic capillary density was
      greater in the ADRC group than in the phosphate-buffered saline control group
      (P<0.01). Tissue expression of vascular endothelial growth factor C mRNA and
      plasma levels of vascular endothelial growth factor C were greater in the ADRC
      group than in the control group (P<0.01 and P<0.05, respectively). ADRCs released
      vascular endothelial growth factor C, which directly stimulated
      lymphangiogenesis. Implantation of ADRCs also enhanced recruitment of bone marrow
      derived M2 macrophages, which served as lymphatic endothelial progenitor cells.
      CONCLUSIONS: Implantation of autologous ADRCs could be a useful treatment option
      for patients with severe lymphedema via mediation of lymphangiogenesis. (J Am
      Heart Assoc. 2012;1:e000877 doi: 10.1161/JAHA.112.000877.).

PMID- 23130157
TI  - Arginase II Promotes Macrophage Inflammatory Responses Through Mitochondrial
      Reactive Oxygen Species, Contributing to Insulin Resistance and Atherogenesis.
AB  - BACKGROUND: Macrophage-mediated chronic inflammation is mechanistically linked to
      insulin resistance and atherosclerosis. Although arginase I is considered
      antiinflammatory, the role of arginase II (Arg-II) in macrophage function remains
      elusive. This study characterizes the role of Arg-II in macrophage inflammatory
      responses and its impact on obesity-linked type II diabetes mellitus and
      atherosclerosis. METHODS AND RESULTS: In human monocytes, silencing Arg-II
      decreases the monocytes' adhesion to endothelial cells and their production of
      proinflammatory mediators stimulated by oxidized low-density lipoprotein or
      lipopolysaccharides, as evaluated by real-time quantitative reverse transcription
      polymerase chain reaction and enzyme-linked immunosorbent assay. Macrophages
      differentiated from bone marrow cells of Arg-II-deficient (Arg-II(-/-)) mice
      express lower levels of lipopolysaccharide-induced proinflammatory mediators than
      do macrophages of wild-type mice. Importantly, reintroducing Arg-II cDNA into Arg
      II(-/-) macrophages restores the inflammatory responses, with concomitant
      enhancement of mitochondrial reactive oxygen species. Scavenging of reactive
      oxygen species by N-acetylcysteine prevents the Arg-II-mediated inflammatory
      responses. Moreover, high-fat diet-induced infiltration of macrophages in various
      organs and expression of proinflammatory cytokines in adipose tissue are blunted
      in Arg-II(-/-) mice. Accordingly, Arg-II(-/-) mice reveal lower fasting blood
      glucose and improved glucose tolerance and insulin sensitivity. Furthermore,
      apolipoprotein E (ApoE)-deficient mice with Arg-II deficiency (ApoE(-/-)Arg-II(-/
      )) display reduced lesion size with characteristics of stable plaques, such as
      decreased macrophage inflammation and necrotic core. In vivo adoptive transfer
      experiments reveal that fewer donor ApoE(-/-)Arg-II(-/-) than ApoE(-/-)Arg
      II(+/+) monocytes infiltrate into the plaque of ApoE(-/-)Arg-II(+/+) mice.
      Conversely, recipient ApoE(-/-)Arg-II(-/-) mice accumulate fewer donor monocytes
      than do recipient ApoE(-/-)Arg-II(+/+) animals. CONCLUSIONS: Arg-II promotes
      macrophage proinflammatory responses through mitochondrial reactive oxygen
      species, contributing to insulin resistance and atherogenesis. Targeting Arg-II
      represents a potential therapeutic strategy in type II diabetes mellitus and
      atherosclerosis. (J Am Heart Assoc. 2012;1:e000992 doi:
      10.1161/JAHA.112.000992.).

PMID- 23130158
TI  - CaMK4 Gene Deletion Induces Hypertension.
AB  - BACKGROUND: The expression of calcium/calmodulin-dependent kinase IV (CaMKIV) was
      hitherto thought to be confined to the nervous system. However, a recent genome
      wide analysis indicated an association between hypertension and a single
      nucleotide polymorphism (rs10491334) of the human CaMKIV gene (CaMK4), which
      suggests a role for this kinase in the regulation of vascular tone. METHODS AND
      RESULTS: To directly assess the role of CaMKIV in hypertension, we characterized
      the cardiovascular phenotype of CaMK4(-/-) mice. They displayed a typical
      hypertensive phenotype, including high blood pressure levels, cardiac
      hypertrophy, vascular and kidney damage, and reduced tolerance to chronic
      ischemia and myocardial infarction compared with wild-type littermates.
      Interestingly, in vitro experiments showed the ability of this kinase to activate
      endothelial nitric oxide synthase. Eventually, in a population study, we found
      that the rs10491334 variant associates with a reduction in the expression levels
      of CaMKIV in lymphocytes from hypertensive patients. CONCLUSIONS: Taken together,
      our results provide evidence that CaMKIV plays a pivotal role in blood pressure
      regulation through the control of endothelial nitric oxide synthase activity. (J
      Am Heart Assoc. 2012;1:e001081 doi: 10.1161/JAHA.112.001081.).

PMID- 23130159
TI  - Trends in clinical, demographic, and biochemical characteristics of patients with
      acute myocardial infarction from 2003 to 2008: a report from the american heart
      association get with the guidelines coronary artery disease program.
AB  - BACKGROUND: An analysis of the changes in the clinical and demographic
      characteristics of patients with acute myocardial infarction could identify
      successes and failures of risk factor identification and treatment of patients at
      increased risk for cardiovascular events. METHODS AND RESULTS: We reviewed data
      collected from 138 122 patients with acute myocardial infarction admitted from
      2003 to 2008 to hospitals participating in the American Heart Association Get
      With The Guidelines Coronary Artery Disease program. Clinical, demographic, and
      laboratory characteristics were analyzed for each year stratified on the
      electrocardiogram at presentation. Patients with non-ST-segment-elevation
      myocardial infarction were older, more likely to be women, and more likely to
      have hypertension, diabetes mellitus, and a history of past cardiovascular
      disease than were patients with ST-elevation myocardial infarction. In the
      overall patient sample, significant trends were observed of an increase over time
      in the proportions of non-ST-segment-elevation myocardial infarction, patient age
      of 45 to 65 years, obesity, and female sex. The prevalence of diabetes mellitus
      decreased over time, whereas the prevalences of hypertension and smoking were
      substantial and unchanging. The prevalence of "low" high-density lipoprotein
      increased over time, whereas that of "high" low-density lipoprotein decreased.
      Stratum-specific univariate analysis revealed quantitative and qualitative
      differences between strata in time trends for numerous demographic, clinical, and
      biochemical measures. On multivariable analysis, there was concordance between
      strata with regard to the increase in prevalence of patients 45 to 65 years of
      age, obesity, and "low" high-density lipoprotein and the decrease in prevalence
      of "high" low-density lipoprotein. However, changes in trends in age
      distribution, sex ratio, and prevalence of smokers and the magnitude of change in
      diabetes mellitus prevalence differed between strata. CONCLUSIONS: There were
      notable differences in risk factors and patient characteristics among patients
      with ST-elevation myocardial infarction and those with non-ST-segment-elevation
      myocardial infarction. The increasing prevalence of dysmetabolic markers in a
      growing proportion of patients with acute myocardial infarction suggests further
      opportunities for risk factor modification. (J Am Heart Assoc. 2012;1:e001206
      doi: 10.1161/JAHA.112.001206.).

PMID- 23130160
TI  - Mild sensory stimulation protects the aged rodent from cortical ischemic stroke
      after permanent middle cerebral artery occlusion.
AB  - BACKGROUND: Accumulated research has shown that the older adult brain is
      significantly more vulnerable to stroke than the young adult brain. Although
      recent evidence in young adult rats demonstrates that single-whisker stimulation
      can result in complete protection from ischemic damage after permanent middle
      cerebral artery occlusion (pMCAO), it remains unclear whether the same treatment
      would be effective in older animals. METHODS AND RESULTS: Aged rats (21 to 24
      months of age) underwent pMCAO and subsequently were divided into "treated" and
      "untreated" groups. Treated aged rats received intermittent single-whisker
      stimulation during a 120-minute period immediately after pMCAO, whereas untreated
      aged rats did not. These animals were assessed using a battery of behavioral
      tests 1 week before and 1 week after pMCAO, after which their brains were stained
      for infarct. An additional treated aged group and a treated young adult group
      also were imaged with functional imaging. Results demonstrated that the recovery
      of treated aged animals was indistinguishable from that of the treated young
      adult animals. Treated aged rats had fully intact sensorimotor behavior and no
      infarct, whereas untreated aged rats were impaired and sustained cortical
      infarct. CONCLUSIONS: Taken together, our results confirm that single-whisker
      stimulation is protective in an aged rodent pMCAO model, despite age-associated
      stroke vulnerability. These findings further suggest potential for translation to
      the more clinically relevant older adult human population. (J Am Heart Assoc.
      2012;1:e001255 doi: 10.1161/JAHA.112.001255.).

PMID- 23130161
TI  - Cardiorespiratory fitness and long-term survival in "low-risk" adults.
AB  - BACKGROUND: We sought to establish whether cardiorespiratory fitness had
      important implications for long-term cardiovascular risk among individuals
      classified as low risk by the Framingham Risk Score (10-year coronary heart
      disease risk <10%). Prognostic factors of long-term cardiovascular risk are
      needed for low-risk subjects who make up the largest percentage of the US
      population. METHODS AND RESULTS: The study population was composed of men and
      women, 30 to 50 years of age, who had a baseline medical exam at the Cooper
      Clinic, Dallas, TX, between 1970 and 1983. Eligible individuals were defined as
      at low risk for coronary heart disease by Framingham Risk Score at the time of
      study entry and had no history of diabetes (n=11 190). Cardiorespiratory fitness
      was determined by maximum graded exercise treadmill tests. Over an average 27+/-2
      year period, 15% of low-fit (quintile 1) compared to 6% of high-fit (quintile 5)
      individuals died (P<0.001). A 1-metabolic equivalent level increase in baseline
      fitness was associated with an 11% reduction in all-cause deaths and an 18%
      reduction in deaths due to cardiovascular disease (CVD) after adjustment for age,
      sex, body mass index, systolic blood pressure, total cholesterol, blood glucose
      levels, smoking, and early family history of coronary disease. There was an
      incremental decrease in CVD risk with increasing fitness quintile, such that the
      high fit had the lowest adjusted 30-year CVD mortality rate (hazard ratio 0.29,
      95% CI: 0.16-0.51) compared to the low fit. CONCLUSIONS: Cardiorespiratory
      fitness is associated with a significant reduction in long-term CVD among
      individuals identified as low risk by Framingham Risk Score. These data suggest
      that preventive lifestyle interventions geared to optimize cardiorespiratory
      fitness, even among a "low-risk" subset, should be considered to improve CVD-free
      survival. (J Am Heart Assoc. 2012;1:e001354 doi: 10.1161/JAHA.112.001354.).

PMID- 23130162
TI  - Changes in carotid intima-media thickness during the cardiac cycle: the multi
      ethnic study of atherosclerosis.
AB  - BACKGROUND: Common carotid artery intima-media thickness (IMT), a measure of
      subclinical cardiovascular disease, changes during the cardiac cycle. The
      magnitude of this effect and its implications have not been well studied. METHODS
      AND RESULTS: Far-wall IMT measurements of the right common carotid artery were
      measured at end diastole and peak systole in 5633 individuals from the Multi
      Ethnic Study of Atherosclerosis (MESA). Multivariable regression models were
      generated with end-diastolic IMT, peak-systolic IMT, and change in IMT during the
      cardiac cycle as dependent variables and traditional cardiovascular risk factors
      as independent variables. The average age of our population was 61.9 (45 to 84)
      years. Average change in carotid IMT during the cardiac cycle was 0.041 mm (95%
      confidence interval: 0.039 to 0.042 mm), with a mean IMT of 0.68 mm. End
      diastolic IMT and peak-systolic IMT were similarly associated with risk factors.
      In a fully adjusted model, change in carotid IMT during the cardiac cycle was
      associated with ethnicity and pulse pressure (P=0.001) and not age, sex, or other
      risk factors. Chinese and Hispanics had less of a change in IMT than did non
      Hispanic whites. With peak-systolic IMT reference values used as normative data,
      31.3% more individuals were classified as being in the upper quartile of IMT and
      at high risk for cardiovascular disease than would be expected when IMT is
      measured at end diastole. CONCLUSIONS: Measurable differences in IMT are seen
      during the cardiac cycle. This affects the interpretation of IMT measurements
      used for cardiovascular risk assessment, given published normative data with IMT
      measured at peak systole. CLINICAL TRIAL REGISTRATION: URL:
      www.ClinicalTrials.gov. Unique identifier: NCT00063440. (J Am Heart Assoc.
      2012;1:e001420 doi: 10.1161/JAHA.112.001420.).

PMID- 23130163
TI  - A novel surface electrocardiogram-based marker of ventricular arrhythmia risk in
      patients with ischemic cardiomyopathy.
AB  - BACKGROUND: Better sudden cardiac death risk markers are needed in ischemic
      cardiomyopathy (ICM). Increased heterogeneity of electrical restitution is an
      important mechanism underlying the risk of ventricular arrhythmia (VA). Our aim
      was to develop and test a novel quantitative surface electrocardiogram-based
      measure of VA risk in patients with ICM: the Regional Restitution Instability
      Index (R2I2). METHODS AND RESULTS: R2I2, the mean of the standard deviation of
      residuals from the mean gradient for each ECG lead at a range of diastolic
      intervals, was measured retrospectively from high-resolution 12-lead ECGs
      recorded during an electrophysiology study. Patient groups were as follows: Study
      group, 26 patients with ICM being assessed for implantable defibrillator; Control
      group, 29 patients with supraventricular tachycardia undergoing electrophysiology
      study; and Replication group, 40 further patients with ICM. R2I2 was
      significantly higher in the Study patients than in Controls (mean +/- standard
      error of the mean: 1.09+/-0.06 versus 0.63+/-0.04, P<0.001). Over a median follow
      up period of 23 months, 6 of 26 Study group patients had VA or death. R2I2
      predicted VA or death independently of demographic factors, electrophysiology
      study result, left ventricular ejection fraction, or QRS duration (Cox model,
      P=0.029). R2I2 correlated with peri-infarct zone as assessed by cardiac magnetic
      resonance imaging (r=0.51, P=0.024). The findings were replicated in the
      Replication group: R2I2 was significantly higher in 11 of 40 Replication patients
      experiencing VA (1.18+/-0.10 versus 0.92+/-0.05, P=0.019). In combined analysis
      of ICM cohorts, R2I2 >=1.03 identified subjects with significantly higher risk of
      VA or death (43%) compared with R2I2 <1.03 (11%) (P=0.004). CONCLUSIONS: In this
      pilot study, we have developed a novel VA risk marker, R2I2, and have shown that
      it correlated with a structural measure of arrhythmic risk and predicted risk of
      VA or death in patients with ICM. R2I2 may improve risk stratification and merits
      further evaluation. (J Am Heart Assoc. 2012;1:e001552 doi:
      10.1161/JAHA.112.001552.).

PMID- 23130164
TI  - Measurement of reverse cholesterol transport pathways in humans: in vivo rates of
      free cholesterol efflux, esterification, and excretion.
AB  - BACKGROUND: Reverse cholesterol transport from peripheral tissues is considered
      the principal atheroprotective mechanism of high-density lipoprotein, but
      quantifying reverse cholesterol transport in humans in vivo remains a challenge.
      We describe here a method for measuring flux of cholesterol though 3 primary
      components of the reverse cholesterol transport pathway in vivo in humans: tissue
      free cholesterol (FC) efflux, esterification of FC in plasma, and fecal sterol
      excretion of plasma-derived FC. METHODS AND RESULTS: A constant infusion of [2,3
      (13)C(2)]-cholesterol was administered to healthy volunteers. Three-compartment
      SAAM II (Simulation, Analysis, and Modeling software; SAAM Institute, University
      of Washington, WA) fits were applied to plasma FC, red blood cell FC, and plasma
      cholesterol ester (13)C-enrichment profiles. Fecal sterol excretion of plasma
      derived FC was quantified from fractional recovery of intravenous [2,3-(13)C(2)]
      cholesterol in feces over 7 days. We examined the key assumptions of the method
      and evaluated the optimal clinical protocol and approach to data analysis and
      modeling. A total of 17 subjects from 2 study sites (n=12 from first site, age 21
      to 75 years, 2 women; n=5 from second site, age 18 to 70 years, 2 women) were
      studied. Tissue FC efflux was 3.79+/-0.88 mg/kg per hour (mean +/- standard
      deviation), or ?8 g/d. Red blood cell-derived flux into plasma FC was 3.38+/-1.10
      mg/kg per hour. Esterification of plasma FC was ?28% of tissue FC efflux (1.10+/
      0.38 mg/kg per hour). Recoveries were 7% and 12% of administered [2,3-(13)C(2)]
      cholesterol in fecal bile acids and neutral sterols, respectively. CONCLUSIONS:
      Three components of systemic reverse cholesterol transport can be quantified,
      allowing dissection of this important function of high-density lipoprotein in
      vivo. Effects of lipoproteins, genetic mutations, lifestyle changes, and drugs on
      these components can be assessed in humans. (J Am Heart Assoc. 2012;1:e001826
      doi: 10.1161/JAHA.112.001826.).

PMID- 23130165
TI  - Impact of chronic kidney disease on risk of incident atrial fibrillation and
      subsequent survival in medicare patients.
AB  - BACKGROUND: Atrial fibrillation (AF) and chronic kidney disease (CKD) are
      prevalent in the elderly and are independently associated with increased risk of
      death. We evaluated risk of incident AF with advancing CKD and examined the
      mortality rate associated with CKD after incident AF in elderly patients. METHODS
      AND RESULTS: This retrospective cohort study used the Medicare 5% database. Point
      prevalent Medicare enrollees on December 31, 2006, without preexistent AF or end
      stage renal disease were followed up for incident AF through 2008. CKD and AF
      were identified from International Classification of Diseases, Ninth Revision,
      Clinical Modification diagnosis codes. Associations between CKD stage and
      incident AF and subsequent risk of death were examined in a Cox proportional
      hazards model. Unadjusted survival after incident AF was estimated by the Kaplan
      Meier method. CKD was present in 55 962 patients (5.1% of the cohort). Of these,
      4952 (8.8%) had CKD stages 1 and 2; 19 795 (35.3%), stages 3 to 5; and 31 215
      (55.7%), unknown stage. The hazard ratio for incident AF in CKD stages 3 to 5 was
      1.13 (95% confidence interval 1.09 to 1.18). Other stages were not independently
      associated with incident AF. Survival after incident AF decreased progressively
      as CKD stage increased (P<0.0001). The 1-year mortality rate for CKD stages 3 to
      5 with incident AF was 35.6%. Adjusted hazard ratios for death after incident AF
      were 1.14 (95% confidence interval 1.00 to 1.30) for CKD stages 1 and 2, 1.27
      (95% confidence interval 1.20 to 1.35) for CKD stages 3 to 5, and 1.29 (95%
      confidence interval 1.23 to 1.36) for unknown stage. CONCLUSIONS: Advanced CKD is
      associated with increased risk of incident AF. In Medicare patients with incident
      AF, mortality rates are higher for those with advanced CKD than for those without
      CKD. (J Am Heart Assoc. 2012;1:e002097 doi: 10.1161/JAHA.112.002097.).

PMID- 23130166
TI  - Microvascular Resistance Predicts Myocardial Salvage and Infarct Characteristics
      in ST-Elevation Myocardial Infarction.
AB  - BACKGROUND: The pathophysiology of myocardial injury and repair in patients with
      ST-elevation myocardial infarction is incompletely understood. We investigated
      the relationships among culprit artery microvascular resistance, myocardial
      salvage, and ventricular function. METHODS AND RESULTS: The index of
      microvascular resistance (IMR) was measured by means of a pressure- and
      temperature-sensitive coronary guidewire in 108 patients with ST-elevation
      myocardial infarction (83% male) at the end of primary percutaneous coronary
      intervention. Paired cardiac MRI (cardiac magnetic resonance) scans were
      performed early (2 days; n=108) and late (3 months; n=96) after myocardial
      infarction. T(2)-weighted- and late gadolinium-enhanced cardiac magnetic
      resonance delineated the ischemic area at risk and infarct size, respectively.
      Myocardial salvage was calculated by subtracting infarct size from area at risk.
      Univariable and multivariable models were constructed to determine the impact of
      IMR on cardiac magnetic resonance-derived surrogate outcomes. The median
      (interquartile range) IMR was 28 (17-42) mm Hg/s. The median (interquartile
      range) area at risk was 32% (24%-41%) of left ventricular mass, and the
      myocardial salvage index was 21% (11%-43%). IMR was a significant multivariable
      predictor of early myocardial salvage, with a multiplicative effect of 0.87 (95%
      confidence interval 0.82 to 0.92) per 20% increase in IMR; P<0.001. In patients
      with anterior myocardial infarction, IMR was a multivariable predictor of early
      and late myocardial salvage, with multiplicative effects of 0.82 (95% confidence
      interval 0.75 to 0.90; P<0.001) and 0.92 (95% confidence interval 0.88 to 0.96;
      P<0.001), respectively. IMR also predicted the presence and extent of
      microvascular obstruction and myocardial hemorrhage. CONCLUSION: Microvascular
      resistance measured during primary percutaneous coronary intervention
      significantly predicts myocardial salvage, infarct characteristics, and left
      ventricular ejection fraction in patients with ST-elevation myocardial
      infarction. (J Am Heart Assoc. 2012;1:e002246 doi: 10.1161/JAHA.112.002246).

PMID- 23130167
TI  - Patterns, predictors, variations, and temporal trends in emergency medical
      service hospital prenotification for acute ischemic stroke.
AB  - BACKGROUND#ENTITYSTARTX02014;: Emergency medical services (EMS) hospital
      prenotification of an incoming stroke patient is guideline recommended as a means
      of increasing the timeliness with which stroke patients are evaluated and
      treated. Still, data are limited with regard to national use of, variations in,
      and temporal trends in EMS prenotification and associated predictors of its use. 
      METHODS AND RESULTS#ENTITYSTARTX02014;: We examined 371 988 patients with acute
      ischemic stroke who were transported by EMS and enrolled in 1585 hospitals
      participating in Get With The Guidelines-Stroke from April 1, 2003, through March
      31, 2011. Prenotification occurred in 249 197 EMS-transported patients (67.0%)
      and varied widely by hospital (range, 0% to 100%). Substantial variations by
      geographic regions and by state, ranging from 19.7% in Washington, DC, to 93.4%
      in Montana, also were noted. Patient factors associated with lower use of
      prenotification included older age, diabetes mellitus, and peripheral vascular
      disease. Prenotification was less likely for black patients than for white
      patients (adjusted odds ratio 0.94, 95% confidence interval 0.92-0.97, P<0.0001).
      Hospital factors associated with greater EMS prenotification use were absence of
      academic affiliation, higher annual volume of tissue plasminogen activator
      administration, and geographic location outside the Northeast. Temporal
      improvements in prenotification rates showed a modest general increase, from
      58.0% in 2003 to 67.3% in 2011 (P temporal trend <0.0001). 
      CONCLUSIONS#ENTITYSTARTX02014;: EMS hospital prenotification is guideline
      recommended, yet among patients transported to Get With The Guidelines-Stroke
      hospitals it is not provided for 1 in 3 EMS-arriving patients with acute ischemic
      stroke and varies substantially by hospital, state, and region. These results
      support the need for enhanced implementation of stroke systems of care. (J Am
      Heart Assoc. 2012;1:e002345 doi: 10.1161/JAHA.112.002345.).

PMID- 23130168
TI  - Association of coronary wall shear stress with atherosclerotic plaque burden,
      composition, and distribution in patients with coronary artery disease.
AB  - BACKGROUND: Extremes of wall shear stress (WSS) have been associated with plaque
      progression and transformation, which has raised interest in the clinical
      assessment of WSS. We hypothesized that calculated coronary WSS is predicted only
      partially by luminal geometry and that WSS is related to plaque composition.
      METHODS AND RESULTS: Twenty-seven patients with coronary artery disease underwent
      virtual histology intravascular ultrasound and Doppler velocity measurement for
      computational fluid dynamics modeling for WSS calculation in each virtual
      histology intravascular ultrasound segment (N=3581 segments). We assessed the
      association of WSS with plaque burden and distribution and with plaque
      composition. WSS remained relatively constant across the lower 3 quartiles of
      plaque burden (P=0.08) but increased in the highest quartile of plaque burden
      (P<0.001). Segments distal to lesions or within bifurcations were more likely to
      have low WSS (P<0.001). However, the majority of segments distal to lesions (80%)
      and within bifurcations (89%) did not exhibit low WSS. After adjustment for
      plaque burden, there was a negative association between WSS and percent necrotic
      core and calcium. For every 10 dynes/cm(2) increase in WSS, percent necrotic core
      decreased by 17% (P=0.01), and percent dense calcium decreased by 17% (P<0.001).
      There was no significant association between WSS and percent of fibrous or
      fibrofatty plaque components (P=NS). CONCLUSIONS: IN PATIENTS WITH CORONARY
      ARTERY DISEASE: (1) Luminal geometry predicts calculated WSS only partially,
      which suggests that detailed computational techniques must be used to calculate
      WSS. (2) Low WSS is associated with plaque necrotic core and calcium, independent
      of plaque burden, which suggests a link between WSS and coronary plaque
      phenotype. (J Am Heart Assoc. 2012;1:e002543 doi: 10.1161/JAHA.112.002543.).

PMID- 23130169
TI  - Renalase lowers ambulatory blood pressure by metabolizing circulating adrenaline.
AB  - BACKGROUND: Blood pressure is acutely regulated by the sympathetic nervous system
      through the action of vasoactive hormones such as epinephrine, norepinephrine,
      and dopamine. Renalase, a recently described, secreted flavoprotein, acutely
      decreases systemic pressure when administered in vivo. Single-nucleotide
      polymorphisms present in the gene are associated with hypertension, cardiac
      disease, and diabetes. Although renalase's crystal structure was recently solved,
      its natural substrate(s) remains undefined. METHODS AND RESULTS: Using in vitro
      enzymatic assays and in vivo administration of recombinant renalase, we show that
      the protein functions as a flavin adenine dinucleotide- and nicotinamide adenine
      dinucleotide-dependent oxidase that lowers blood pressure by degrading plasma
      epinephrine. The enzyme also metabolizes the dopamine precursor l-3,4
      dihydroxyphenylalanine but has low activity against dopamine and does not
      metabolize norepinephrine. To test if epinephrine and l-3,4
      dihydroxyphenylalanine were renalase's only substrates, 17 246 unique small
      molecules were screened. Although the search revealed no additional, naturally
      occurring compounds, it identified dobutamine, isoproterenol, and alpha
      methyldopa as substrates of renalase. Mutational analysis was used to test if
      renalase's hypotensive effect correlated with its enzymatic activity. Single
      amino acid mutations that decrease its enzymatic activity to varying degrees
      comparably reduce its hypotensive effect. CONCLUSIONS: Renalase metabolizes
      circulating epinephrine and l-3,4-dihydroxyphenylalanine, and its capacity to
      decrease blood pressure is directly correlated to its enzymatic activity. These
      findings highlight a previously unrecognized mechanism for epinephrine metabolism
      and blood pressure regulation, expand our understanding of the sympathetic
      nervous system, and could lead to the development of novel therapeutic modalities
      for the treatment of hypertension. (J Am Heart Assoc. 2012;1:e002634 doi:
      10.1161/JAHA.112.002634.).

PMID- 23130170
TI  - Association between depression and peripheral artery disease: insights from the
      heart and soul study.
AB  - BACKGROUND: Depression is known to increase the risk of coronary artery disease,
      but few studies have evaluated the association between depression and peripheral
      artery disease (PAD). We examined the association of depression with PAD and
      evaluated potential mediators of this association. METHODS AND RESULTS: We used
      data from the Heart and Soul Study, a prospective cohort of 1024 men and women
      with coronary artery disease recruited in 2000-2002 and followed for a mean of
      7.2+/-2.6 years. Depressive symptoms were assessed with the validated 9-item
      Patient Health Questionnaire. Prevalent PAD at baseline was determined by self
      report. Prospective PAD events were adjudicated on the basis of review of medical
      records. We used logistic regression and Cox proportional-hazards models to
      estimate the independent associations of depressive symptoms with prevalent PAD
      and subsequent PAD events. At baseline, 199 patients (19%) had depressive
      symptoms (Patient Health Questionnaire >=10). Prevalent PAD was reported by 12%
      of patients with depression and 7% of those without depression (base model
      adjusted for age and sex: odds ratio 1.79, 95% confidence interval 1.06-3.04,
      P=0.03; full model adjusted for comorbidities, medications, PAD risk factors,
      inflammation, and health behaviors: odds ratio 1.59, 95% confidence interval 0.90
      2.83, P=0.11). During follow-up, PAD events occurred in 7% of patients with
      depression and 5% of those without depression (base model adjusted for age and
      sex: hazard ratio 2.09, 95% confidence interval 1.09-4.00, P=0.03; full model
      adjusted for comorbidities, medications, PAD risk factors, inflammation, and
      health behaviors: hazard ratio 1.33, 95% confidence interval 0.65-2.71, P=0.44).
      Factors explaining >5% of the association between depression and incident PAD
      events included race/ethnicity, diabetes, congestive heart failure, high-density
      lipoprotein, triglyceride levels, serum creatinine, inflammation, smoking, and
      levels of physical activity. CONCLUSIONS: Depressive symptoms were associated
      with a greater risk of PAD. Because the association was explained partly by
      modifiable risk factors, our findings suggest that more aggressive treatment of
      these risk factors could reduce the excess risk of PAD associated with
      depression. (J Am Heart Assoc. 2012;1:e002667 doi: 10.1161/JAHA.112.002667.).

PMID- 23130171
TI  - Treatment of small ruptured intracranial aneurysms: comparison of surgical and
      endovascular options.
AB  - BACKGROUND: Small intracranial aneurysms pose significant challenges to
      endovascular therapy. Surgical clipping is considered by many to be the preferred
      treatment for these lesions. We present the results of the first study comparing
      the 2 treatment modalities in small ruptured aneurysms. METHODS AND RESULTS:
      Between 2004 and 2011, 151 patients with small ruptured aneurysms (<=3 mm) were
      treated in our institution: 91 (60.3%) with endovascular therapy and 60 (39.7%)
      with surgical clipping. The surgical and endovascular groups were generally
      comparable with regard to baseline demographics, with the exception of larger
      mean aneurysm size in the endovascular group versus the surgical group (2.8
      versus 2.5 mm, respectively; P<0.001) and a higher proportion of posterior
      circulation aneurysms in the endovascular group. Endovascular treatment failed in
      9.9% of patients. Procedure-related complications occurred in 23.3% of surgical
      patients versus 9.8% of endovascular patients (P=0.01). Only 3.7% of patients
      undergoing endovascular therapy experienced an intraprocedural aneurysm rupture.
      There were no procedural deaths or rehemorrhages in either group. The rates of
      aneurysm recanalization and retreatment after endovascular therapy were 18.2% and
      12.7%, respectively. Favorable outcomes (moderate, mild, or no disability) were
      not statistically different between the endovascular (67.1%) and surgical (56.7%)
      groups (P=0.3). CONCLUSIONS: Surgical clipping was associated with a higher rate
      of periprocedural complications, but overall disability outcomes were similar.
      Endovascular therapy, if technically feasible, might be a preferred option in
      this setting. Inclusion of patients with small aneurysms in randomized controlled
      trials seems feasible and will be needed to provide definitive information on the
      best therapeutic approach. (J Am Heart Assoc. 2012;1:e002865 doi:
      10.1161/JAHA.112.002865.).

PMID- 23130172
TI  - Peroxisome Proliferator-Activated Receptor-alpha Agonism With Fenofibrate Does
      Not Suppress Inflammatory Responses to Evoked Endotoxemia.
AB  - BACKGROUND: Data conflict with regard to whether peroxisome proliferator
      activated receptor-alpha agonism suppresses inflammation in humans. We
      hypothesized that in healthy adults peroxisome proliferator-activated receptor
      alpha agonism with fenofibrate would blunt the induced immune responses to
      endotoxin (lipopolysaccharide [LPS]), an in vivo model for the study of
      cardiometabolic inflammation. METHODS AND RESULTS: In the Fenofibrate and omega-3
      Fatty Acid Modulation of Endotoxemia (FFAME) trial, 36 healthy volunteers (mean
      age 26+/-7 years, mean body mass index 24+/-3 kg/m(2), 44% female, 72% white)
      were randomized to fenofibrate 145 mg or placebo daily. After 6 to 8 weeks of
      treatment, subjects underwent a low-dose LPS challenge. Clinical and blood
      measurements were collected at randomization, before LPS administration, and
      serially for 24 hours after LPS administration. We examined area under the curve
      for evoked responses by treatment group. Compared to placebo, but before LPS
      challenge, fenofibrate reduced total cholesterol and tended to decrease
      triglycerides, consistent with achieved therapeutic plasma levels of fenofibric
      acid. In the placebo group, LPS induced a modest inflammatory response with
      increased cytokines and chemokines (2- to 4-hour post-LPS 8-fold increase in
      tumor necrosis factor-alpha, 9-fold increase in interleukin-6, 9-fold increase in
      interleukin-10, and 10-fold increase in monocyte chemotactic protein-1; all
      P<0.001) and acute-phase reactants (24-hour post-LPS 15-fold increase in serum
      amyloid A and 9-fold increase in C-reactive protein; both P<0.001). Compared to
      placebo, however, fenofibrate did not significantly attenuate LPS-induced levels
      of plasma cytokines, chemokines, or acute-phase proteins. CONCLUSIONS: These data
      suggest a lack of systemic antiinflammatory properties of fenofibrate at
      clinically relevant dosing in humans. CLINICAL TRIAL REGISTRATION: URL:
      http://clinicaltrials.gov/ct2/show/NCT01048502. Unique identifier: NCT01048502.
      (J Am Heart Assoc. 2012;1:e002923 doi: 10.1161/JAHA.112.002923.).

PMID- 23130173
TI  - Spatial heterogeneity of electrical restitution as a predictor of ventricular
      tachyarrhythmias: a lumped-parameter approach.

PMID- 23130175
TI  - And what about exercise? Fitness and risk of death in "low-risk" adults.

PMID- 23130174
TI  - Novel Therapy for Atherosclerosis Using Recombinant Immunotoxin Against Folate
      Receptor beta-Expressing Macrophages.
AB  - BACKGROUND: Folate receptor beta (FRbeta) is induced during macrophage
      activation. A recombinant immunotoxin consisting of the truncated Pseudomonas
      exotoxin A (PE38) conjugated to an anti-FRbeta antibody (anti-FRbeta-PE38) has
      been reported to kill activated macrophages in inflammatory diseases. To
      elucidate the effect of an immunotoxin targeting FRbeta on atherosclerosis, we
      determined the presence of FRbeta-expressing macrophages in atherosclerotic
      lesions and administered the FRbeta immunotoxin in apolipoprotein E-deficient
      mice. METHODS AND RESULTS: The FRbeta-expressing macrophages were observed in
      atherosclerotic lesions of apolipoprotein E-deficient mice. At 15 or 35 weeks of
      age, the apolipoprotein E-deficient mice were divided into 3 groups and were
      intravenously administered 0.1 mg/kg of anti-FRbeta-PE38 (immunotoxin group), 0.1
      mg/kg of PE38 (toxin group), or 0.1 mL of saline (control group) every 3 days,
      for a total of 5 times for each age group. The mice were analyzed at 21 or 41
      weeks of age. Treatment with the immunotoxin resulted in 31% and 22% reductions
      in atherosclerotic lesions of the 21- and 41-week-old mice, respectively
      (P<0.05). Administration of immunotoxin reduced the numbers of FRbeta- and tumor
      necrosis factor-alpha-expressing macrophages, reduced cell proliferation, and
      increased the number of apoptotic cells (P<0.05). Real-time polymerase chain
      reaction demonstrated that the expression of FRbeta and tumor necrosis factor
      alpha mRNA was significantly decreased in the immunotoxin group (P<0.05).
      CONCLUSIONS: These results suggest that FRbeta-expressing macrophages exist in
      the atherosclerotic lesions of apolipoprotein E-deficient mice and that FRbeta
      immunotoxin administration reduces the progression of atherosclerotic lesions in
      younger and older individuals. The recombinant FRbeta immunotoxin targeting
      activated macrophages could provide a novel therapeutic tool for atherosclerosis.
      (J Am Heart Assoc. 2012;1:e003079 doi: 10.1161/JAHA.112.003079.).

PMID- 23130176
TI  - The microvasculature after reperfused myocardial infarction: to examine or not to
      examine?

PMID- 23130177
TI  - Experimental lymphedema: can cellular therapies augment the therapeutic potential
      for lymphangiogenesis?

PMID- 23130179
TI  - Folate receptor: a macrophage "achilles' heel"?

PMID- 23130178
TI  - Tachometer for reverse cholesterol transport?

PMID- 23130180
TI  - Special message.

PMID- 23130181
TI  - From the virtual desk of the editor.

PMID- 23130182
TI  - The skin on the move but cold adapted: Fundamental misconceptions in the
      laboratory and clinic.
AB  - The skin is constantly on the move and at a temperature below 37oC. The epidermis
      is a factory, and its blood supply and lymphatic drainage, as well as adipose
      tissue, are much dependent on movement and influenced by cooling. Neither
      histopathology (still pictures) nor in vitro studies at 37oC reflect the true
      picture. Recent publications neglect older literature exploring these issues.

PMID- 23130183
TI  - Studies on comparison of the efficacy of terbinafine 1% cream and butenafine 1%
      cream for the treatment of Tinea cruris.
AB  - BACKGROUND: In this study, 76 male patients aged between 18 and 61 years affected
      with Tinea cruris attending the outpatient department of NRS Medical College
      during a 1-year period were selected. MATERIALS AND METHODS: The patients were
      divided into two groups as Regimen I (n 37) and Regimen II (n 39) who were
      treated with Terbinafine (gr I) cream and Butenafine (gr II) cream, respectively.
      RESULTS: The predominant pathogen was found to be Trichophyton rubrum in 99% of
      cases. Mycological cure, overall cure and effective treatment were evaluated on
      7, 14 and 42 days. CONCLUSIONS: From the study, it was found that Butenafine
      produced the quickest result and primary efficacy end points were much higher
      with Butenafine cream than that of Terbinafine cream and this difference was
      statistically significant (P < 0.01).

PMID- 23130184
TI  - Infantile systemic hyalinosis: A case report and review of literature.
AB  - We report a case of infantile systemic hyalinosis in a 3.5-month-old male child
      born out of consanguineous marriage. He presented with multiple brownish raised
      lesions over bony prominences. He had also developed difficulty in movement of
      limbs and as a result developed severe flexion joint contractures. There was
      history of similar complaints in elder sibling who died at the age of 5 months
      due to repeated episodes of pneumonia. Skin biopsy from one of the papulonodular
      lesions showed increased amount of amorphous hyaline matrix, which was Periodic
      Acid Schiff positive with scattered fibroblasts. Though classical, we report this
      case for its rarity in western India.

PMID- 23130185
TI  - Lapatinib-induced acute generalized exanthematous pustulosis.
AB  - Acute generalized exanthematous pustulosis (AGEP) is a pustular eruption, mainly
      drug induced often accompanied by fever and neutrophilic leukocytosis presenting
      as scarlatiniform erythema over the flexures evolving into numerous tiny non
      follicular pustules. We present a case report of a 56-year old woman, who had
      undergone mastectomy, treated with lapatinib for metastatic disease, and who
      presented with multiple erythematous papules and plaques with peripheral
      pustules. She also developed painful pyogenic granuloma-like lesions over the
      pulp of toe and over the proximal nail folds.All the lesions subsided following
      withdrawal of lapatinib. Although AGEP has been reported with imatinib (a
      multikinase inhibitor), there have been no reports of serious reactions with
      lapatinib, an EGFR inhibitor. This case could represent the first case report of
      AGEP to the EGFR inhibitor, lapatinib.

PMID- 23130186
TI  - Darier-White disease in siblings responding to isotretinoin.
AB  - Darier-White disease (keratosis follicularis) is a rare disorder of
      keratinization involving the epidermis, mucous membranes, and nails. It is said
      to occur as a result of mutation in the ATP2A2 gene located on chromosome 12q23
      24.1. In this article we present the case of two brothers with exacerbations of
      Darier-White disease who responded very well to systemic retinoids without any
      side effects within 2 weeks of commencing treatment.

PMID- 23130187
TI  - Acral pityriasis rosea in an infant with palmoplantar lesions: A novel
      manifestation.
AB  - Indian children often present with atypical forms of pityriasis rosea (PR). We
      describe a female infant with acrally located eruptions consistent with a
      clinical diagnosis of PR. This is an extremely rare presentation of the disease.

PMID- 23130188
TI  - Fibromyxoid sarcoma of the leg.
AB  - A 48-year-old female with an atypical plaque-like lesion of the lower leg is
      presented in this article. Histologic investigation revealed a rare low-grade
      fibromyxoid sarcoma (pT1a cN0 cM0; stage Ia) of suprafascial localization.
      Staging of the patient did not reveal metastatic spread. The tumor was surgically
      removed with wide safety margins. The defect was closed using a mesh graft
      transplant and vacuum-assisted closure. Healing was complete. Regular follow-up
      for at least 5 years is recommended. Besides the rareness of this tumor, this
      case is also remarkable because of the localization on the lower leg and the
      suprafascial soft tissue.

PMID- 23130189
TI  - Generalized eruptive histiocytoma.
AB  - We are reporting a 62 year old male, who over a period of 1 year, developed a
      symmetric eruption of hundreds of brownish papules, with spontaneous regression
      of some lesions. The clinical and histopathological findings were compatible with
      the diagnosis of generalized eruptive histiocytoma.

PMID- 23130190
TI  - Hematohidrosis: A rare clinical entity.
AB  - Hematohidrosis is a rare clinical condition of sweating blood. A 13-year-old boy
      was presented to the department of dermatology with a history of spontaneous
      bleeding from skin since January 2007. During examination, it disappeared as soon
      as it was mopped leaving behind no sign of trauma only to reappear within a few
      seconds. This confirms that it was sweating of blood and not bleeding. Bleeding
      time, clotting time and prothrombin time was normal. Patient was diagnosed with
      hematohidrosis clinically by exclusion, confirmed by benzidine test, biochemical
      and microscopic examination of fluid. At present, no treatment is available for
      this condition. Etiology is unknown till date. Stress may be a precipitating
      factor.

PMID- 23130191
TI  - Papillon-Lefevre syndrome with pseudoainhum.
AB  - An interesting episode of Papillon-Lefevre syndrome in a 25-year-old female with
      diffuse palmoplantar keratoderma, periodontitis and pseudoainhum of the toes is
      reported for academic interest. Her skin lesions improved with topical
      keratolytics and oral retinoid (acitretin) whereas periodontic problems showed
      significant improvement with systemic antibiotics and proper implementation of
      oral hygienic measures. She is undergoing oral rehabilitation with orthodontic
      surgical procedures.

PMID- 23130192
TI  - Idiopathic calcinosis cutis of the penis.
AB  - Calcification of the skin occurs in four main forms namely dystrophic,
      metastatic, iatrogenic and idiopathic. Idiopathic calcinosis cutis of the penis
      is exceedingly rare as only five cases have been reported till date to the best
      of our knowledge. Herein, we present another case of this rare entity in a 29
      year old man and discuss its probable pathogenic origin.

PMID- 23130193
TI  - Early prenatal syphilis.
AB  - Syphilis in pregnancy still remains a challenge despite the availability of
      adequate diagnostic tests for serological screening and penicillin therapy. We
      report a case of 2 month old female infant who presented with runny nose,
      papulosquamous lesions over both palms and soles and perianal erosions since 1
      month after birth. Cutaneous examination revealed moist eroded areas in the
      perianal region and fine scaly lesions over palms and soles. Radiograph of both
      upper limbs and limbs revealed early periosteal changes in lower end of humerus
      and lower end of tibia. Diagnosis of early pre-natal syphilis was confirmed by
      Child's Serum Rapid Plasma Reagin Antibody test [S.RPR] being positive with 1:64
      dilution while that of mother was 1:8.

PMID- 23130194
TI  - Complication of dimple creation.

PMID- 23130195
TI  - Progressive and symmetric erythrokeratoderma of adult onset: A rare case.

PMID- 23130196
TI  - Fexofenadine in higher doses in chronic spontaneous urticaria.

PMID- 23130197
TI  - Multiple coalescing Herald patches.

PMID- 23130198
TI  - SKINDIA QUIZ 1: Erythematous, firm, papular eruptions involving the face, neck
      and chest.

PMID- 23130199
TI  - Cost-effective use of scalp lotions-Some points to ponder.

PMID- 23130200
TI  - Sad confusion of look-alike tablets.

PMID- 23130201
TI  - Carotenoderma.

PMID- 23130202
TI  - Reminiscences.

PMID- 23130203
TI  - From the desk of the Editor.

PMID- 23130204
TI  - Acne: Diet and acnegenesis.
AB  - Acne is a manifestation of hormonal overstimulation of the pilosebaceous units of
      genetically susceptible individuals. Endogenous reproductive and growth hormones,
      exogenous reproductive hormones, insulin and endogenous insulin-like growth
      hormone-1, sourced from and stimulated by dairy and high glycemic load foods, all
      appear to contribute to this overstimulation. A postulated molecular mechanism
      linking food and acne is reported and integrated into the clinical picture.

PMID- 23130205
TI  - Nonablative facelift in Indian skin with superpulsed radiofrequency.
AB  - AIMS: To evaluate the effect of nonablative superpulsed radiofrequency used for
      skin tightening and improvement of skin folds in Indian patients. SETTINGS AND
      DESIGN: One hundred patients in the age group of 35-65 years with laxity of skin
      over face and neck were taken up for study using superpulse radiofrequency.
      METHODS AND MATERIALS: Superpulsed radiofrequency is a biterminal, monopolar
      device which delivers current at the frequency of 1.75 MHz. In this study,
      current was delivered to the tissue with a capacitive electrode with a diameter
      of 25 mm. Power of 100-120 W, frequency of 18 Hz and pulse width of 50 ms was
      used. STATISTICAL ANALYSIS USED: Chi-square test, nonparametric Friedman test.
      RESULTS: Evaluation was done by two independent observers on the basis of
      comparative photographs taken before treatment and then monthly after treatment
      for up to 6 months. A quartile grading scale was used. Patient satisfaction
      scores matched the clinical improvements observed. Ninety four patients completed
      a 6 month follow up. The age groups taken were 31-40 years, 41-50 years, 51-60
      years, and >60 years and various areas were studied. The difference in
      improvement in all areas except glabellar folds across all age groups was found
      to be statistically significant. CONCLUSIONS: Nonablative face lift with a
      superpulsed radiofrequency machine is a safe, convenient and quick office
      procedure with excellent cosmetic results. It is noninvasive and there is no
      downtime. It can be used in all skin types and is safe on Indian skin. Longterm
      studies of effect of nonablative radiofrequency treatment on Indian skin is
      required.

PMID- 23130206
TI  - Dexamethasone- cyclophosphamide pulse in collagen vascular diseases: An
      observation.
AB  - BACKGROUND: Treatment of collagen vascular diseases like systemic sclerosis,
      dermatomyositis, systemic lupus erythematosus (SLE) and even overlap syndromes
      has been difficult since long. Monumental success of dexamethasone
      cyclophosphamide pulse (DCP) in pemphigus has prompted many a dermatologist to
      try it in other autoimmune diseases. MATERIALS AND METHODS: DCP was given as per
      standard regimen for six to nine pulses. Immunosuppressives were given for 12-18
      months in dermatomyositis, SLE, and overlap syndrome, and for 12 months in
      systemic sclerosis. Daily dose of steroid was tapered off gradually. RESULTS: The
      treatment resulted in 90% improvement in skin binding in systemic sclerosis, 80%
      in exertional dyspnea, 40% in dysphagia, but minimum improvement was seen in
      Raynauds and digital tip ulcerations. No improvement in pigmentation was noted.
      In SLE, malar rash cleared in 70%, joint pain in 80%, oral ulcerations reduced in
      80%, fever in 98%, and photosensitivity improved in one-third of patients. In
      dermatomyositis, improvement in muscle tenderness was seen in 100%, improvement
      in proximal myopathy and heliotrope rash in 80%, and improvement of shawl sign
      was observed in 80% of the patients. Some flattening of Gottron papules and
      plaques was noted in some patients. Both overlap patients improved significantly.
      Out of 24 patients, three were lost to follow-up, one resorted to homeopathic
      medicine and two expired (one dermatomyositis, one SLE). Side effects like
      hypertension, hyperglycemia, pyoderma, fungal infections, obesity, psychosis,
      etc. were seen in 25-30% of patients. CONCLUSIONS: We conclude that DCP is
      relatively safe, effective as well as cheap compared to methylprednisolone pulse.
      Side effects are also less compared to daily regimen of steroids. We also
      observed that patients who reported early and put on pulse early responded
      better.

PMID- 23130207
TI  - Oxcarbazepine-induced Stevens Johnson syndrome: A rare case report.
AB  - Although carbamazepine is the most common cause of Stevens Johnson syndrome (SJS)
      a new antiepileptic drug, oxcarbazepine which is structurally related to
      carbamazepine, has also been rarely shown to induce SJS. Here we report a case
      with SJS, which was induced by oxcarbazepine.

PMID- 23130208
TI  - Localized psoriasis herpeticum: Case report and review of literature.
AB  - Kaposi's varicelliform eruption (KVE) is a widespread cutaneous eruption caused
      by viruses, especially herpes simplex virus in patients with pre-existing
      dermatoses. "Psoriasis herpeticum" refers to the rare occurrence of KVE in
      patients with psoriasis. We report a case of KVE localized to the face in a
      patient with exfoliative dermatitis secondary to psoriasis. This case is being
      reported to make the treating clinician aware of the possibility of KVE in
      patients with psoriatic erythroderma.

PMID- 23130209
TI  - Malignant syphilis with human immunodeficiency virus infection.
AB  - Malignant syphilis or Lues maligna, commonly reported in the pre-antibiotic era,
      has now seen a resurgence with the advent of human immunodeficiency virus (HIV).
      Immunosuppression and sexual promiscuity set the stage for this deadly
      association of HIV and Treponema pallidum that can manifest atypically and can
      prove to cause diagnostic problems. We report one such case in a 30-year-old
      female who responded favorably to treatment with penicillin.

PMID- 23130210
TI  - Faun tail nevus.
AB  - Faun tail nevus is a posterior midline cutaneous lesion of importance to
      dermatologists as it could be a cutaneous marker for its underlying spine and
      spinal cord anomaly. We report a 13-year-old girl with excessive hair growth over
      the lumbosacral region since birth. There was associated spinal anomaly with no
      neurological manifestation affecting the lower spinal cord. The diagnosis was
      made on clinical basis. The patient reported for cosmetic disability. This case
      is reported for its clinical importance.

PMID- 23130211
TI  - Fibrous hamartoma of infancy.
AB  - Fibrous hamartoma of infancy (FHI) is a rare, benign tumor of the subcutis and
      lower dermis, which usually occurs within the first 2 years of life. Ninety one
      percent of the tumors occur in the first year of life. The histogenesis of FHI is
      unclear. The clinical course is typically benign and prognosis excellent. The
      physical characteristics of the subcutaneous mass in a child may suggest a
      malignant process; however, FHI should be included in the differential diagnosis.
      The prognosis of FHI is excellent with local surgical excision and it rarely
      recurs.

PMID- 23130212
TI  - Erythema elevatum diutinum associated with scleritis.
AB  - Erythema elevatum diutinum (EED) is a chronic and rare variant of
      leukocytoclastic vasculitis that is being reported nowadays frequently in
      association with HIV infection. It clinically manifests as asymptomatic to tender
      erythematous papules, plaques and nodules, usually with acral distribution and is
      rarely accompanied by systemic complaints other than arthralgia. The reported
      associations include preceding upper respiratory infections, hematological
      malignancies, lymphomas and monoclonal gammopathies. Here we report a 45 year old
      man with multiple joint pains, tender nodules over palms and soles and ocular
      pain and congestion, who was subsequently diagnosed as a case of EED and
      scleritis following histopathological examination. Skin as well as ocular
      complaints completely subsided with Dapsone monotherapy.

PMID- 23130214
TI  - Steroid card: A simple practice to avoid catastrophe.

PMID- 23130213
TI  - Sjogren-Larsson syndrome: A case report of a rare disease.
AB  - We report a case of Sjogren-Larsson syndrome with clinical profile (spastic
      diplegia, icthyosis, mental retardation) and imaging findings on magnetic
      resonance imaging.

PMID- 23130215
TI  - Perifollicular pigmentation in bullous pemphigoid: A diagnostic sign.

PMID- 23130216
TI  - Netherton syndrome: A rare genodermatosis.

PMID- 23130217
TI  - Bullous oral lichen planus: An unusual variant.

PMID- 23130218
TI  - Lymphangiectasias of vulva.

PMID- 23130219
TI  - Atypical presentation of Becker's melanosis.

PMID- 23130220
TI  - Hailey-Hailey disease: A case treated with topical tacrolimus.

PMID- 23130221
TI  - Panniculitis as the first sign of systemic lupus erythematosus.

PMID- 23130222
TI  - SkIndia Quiz 2 - Asymptomatic skin coloured nodules in a pregnant lady.

PMID- 23130223
TI  - Cutaneous larva migrans (creeping eruption).

PMID- 23130224
TI  - Nephrogenic systemic fibrosis.
AB  - Nephrogenic systemic fibrosis (NSF) is a relatively new fibrosing disorder which
      has caught the attention of various specialities in the past decade. NSF is an
      extremely disabling and often painful condition, affecting up to 13% of the
      individuals with chronic kidney disease. The administration of a gadolinium
      chelate contrast agent has been reported to induce the development of NSF,
      particularly in patients who have acute or chronic renal disease with a
      glomerular filtration rate (GFR) lower than 30-mL/min/1.73 m(2) and in those with
      acute renal insufficiency. Mass spectroscopy studies have demonstrated particles
      of gadolinium in the lesional tissue. The exact pathogenesis of this curious
      sclerosing condition is unknown. The role of the aberrant targeting of
      'circulating fibrocytes' to the peripheral tissues and viscera has been
      hypothesized. NSF has distinct clinicopathological features in the setting of
      renal failure and needs to be looked upon as a new entity on the block. The
      condition is characterized by irregular indurated plaques, with amoeba-like
      projections and islands of sparing, chiefly on the trunk and extremities. Flexion
      contractures of fingers, knees, and elbow joints are known to occur in advanced
      cases of NSF. The course is frequently associated with painful episodes and loss
      of ambulation. Histopathology shows haphazard arrangement of thickened bundles of
      collagen, varying amount of mucin, and increased population of fibroblast-like
      cells in the dermis. Immunohistochemistry shows increased deposition of type-I
      procollagen and CD 34+ cells having fibroblastic activity. The condition is
      refractory to treatment with corticosteroids and immunosuppressive agents.
      Various modalities of therapy such as UVA1 phototherapy, imatinib mesylate,
      photodynamic therapy, plasmapheresis, extracorporeal photochemotherapy, and high
      dose intravenous immunoglobulin have shown a moderate degree of improvement in
      skin thickness scores. A prudent option is restoration of renal function to
      normalcy via renal transplantation but to date the outcome of renal
      transplantation is unknown.

PMID- 23130225
TI  - Genetic screening test for psoriatic arthritis and UVB irradiation potential
      responders: A new tool to identify psoriasis subpopulation patients?
AB  - Psoriatic arthritis (PsA) is a psoriasis-associated inflammatory disease of the
      joints and enthuses. The occurrence of PsA is linked to the complex interplay of
      gene environment, and immune system. Genetic factors have long been recognized to
      play an important role in PsA. Genes within the major histocompatibility complex
      (MHC) region have been shown to be associated with PsA. These include genes coded
      in the HLA region, (especially Class I antigens) and non-HLA genes (i.e., MHC
      class I chain-related antigen A, MICA, and TNF-alpha genes). Association studies
      in PsA have also identified a number of genes outside MHC region, including
      interleukin-1 (IL-1) gene cluster, killer-cell immunoglobulin-like receptors
      (KIRs), and IL-23R genes. Established systemic treatments for moderate-severe
      psoriasis and PsA may be potentially dangerous and usually time consuming for the
      patient and often expensive for the National Health Systems. Tests which could
      predict which subset of psoriatic patients could develop the most severe forms of
      the disease (i.e., PsA) or will respond to well-established (UVB irradiation) or
      other systemic treatments are now required. The goal of genetic test screening is
      to rapidly and safely identify subjects for preventive or early treatment or
      extended surveillance prior to the onset of signs and symptoms. Genetic tests
      today represent a reliable investigation procedure which could rapidly and
      consistently improve the diagnostic ability of the dermatologist and contribute
      to the early and correct treatment of the different subsets of PsA.

PMID- 23130226
TI  - Clinico-etiological study with response to specific treatment in childhood
      urticaria.
AB  - BACKGROUND: Urticaria is a common dermatological manifestation in adults with
      relatively infrequent occurrence of chronic urticaria (CU) in childhood. The
      etiology of urticaria in childhood remains incompletely understood because of
      limited data on children. OBJECTIVE: We carried out this retrospective data-based
      study to determine different etiological factors and response to treatment in
      pediatric patients presenting with urticaria. MATERIALS AND METHODS: EIGHTY
      CHILDREN (M : F 49 : 31) between the ages of 1 and 14 years, who presented with
      urticaria excluding patients of physical urticaria attending the Outpatient
      Department of Pediatrics and Dermatology were included in the study. Patients
      were evaluated after taking a detailed history, doing a thorough physical
      examination, and basic laboratory investigations. Specific in vivo and in vitro
      tests were performed after the initial evaluation and consent of patients.
      RESULTS: Out of eighty patients, 35 (43.75%) presented with acute urticaria and
      45 (56.25%) gave a history of chronic urticaria.CU. An underlying cause was
      suspected in 53 cases (66.25%), although a definite association with response to
      a specific treatment was correlated in 30 (37.5%). Infection was the most common
      underlying causative factor. Underlying thyroid dysfunction was observed in 12
      patients, of whom two had thyroid anti peroxidase antibodies. Autologous serum
      skin test was positive in 17 patients. CONCLUSIONS: In the present study
      infections were the most common etiological factor for urticaria in children.

PMID- 23130227
TI  - Intraocular pressure variation in patients on long-term corticosteroids.
AB  - BACKGROUND: Long-term use of topical and systemic steroids produces secondary
      open-angle glaucoma similar to chronic simple glaucoma. The increased intraocular
      pressure [IOP] caused by prolonged steroid therapy is reversible but the damage
      produced by it is irreversible. MATERIALS AND METHODS: In this study, we analyzed
      200 patients with steroid-induced glaucoma, who were on systemic and topical
      corticosteroids for various dermatological conditions. The variation in IOP
      caused by different steroid preparations was studied. RESULTS: Two hundred
      patients who were on systemic steroids for more than 8 weeks developed raised
      IOP. Three of these patients also developed bilateral posterior subcapsular
      cataract. CONCLUSION: We conclude that systemic steroids can induce rise of IOP
      and cataract formation. If it is not detected and treated in time, rise in IOP
      can lead to irreversible damage to the eyes.

PMID- 23130228
TI  - Community care of the physically disabled due to leprosy.
AB  - This preliminary presentation based on extensive field studies carried out by
      Bombay Leprosy Project, a research-oriented NGO, portrays the alarming dimensions
      of the disease burden felt by rural communities and recommends a cost effective
      field model. This study in an adopted rural population in Shahapur "taluka" of
      Thane District assumes tremendous significance and is worthy of replication in
      comparable situations. This is particularly so in the background of the absence
      in the literature of any similar field studies based entirely on community care
      of the physically disabled due to leprosy. The magnitude of the problem posed by
      leprosy patients with disabilities and their rehabilitation is highly challenging
      and is expected to pose a heavy burden on the community as well as unprecedented
      strain on the PHCs managed by the government. The health planners should rethink
      on future strategies in such a manner that human rights of the downtrodden
      patients suffering from the "neglected disease" of leprosy are not sidelined.

PMID- 23130229
TI  - Pilomatricoma: Forget me not.
AB  - Pilomatricoma is a benign skin neoplasia, which is not commonly encountered in
      general practice. The diagnosis is often made only after histopathology. The
      present case report is of a 30-year-old woman who presented with swelling in
      neck, which was diagnosed as pilomatricoma only after excision. The idea of
      reporting this case is that pilomatricoma is not rare in occurrence but rarely
      diagnosed because of lack of confirmation of excised swelling and it is
      imperative that it should be kept in the differential diagnoses of all
      superficial skin tumors by dermatologists and surgeons.

PMID- 23130230
TI  - Erythema multiforme-like eruption from a slimming drug preparation cutaneous
      adverse drug reaction.
AB  - We report a case of a 34-year-old woman presenting with an erythema multiforme
      (EM)-like eruption. Lesions developed after a 12-day treatment with a slimming
      drug preparation (food integrator with thermogenic activity) and a herbal remedy
      (pilosella tincture). Serological investigations excluded viral or bacterial
      infections. Patch testing with galenic preparations of both drugs demonstrated
      sensitization to the slimming drug preparation. According to literature reports
      and immune-chemical properties, those components that are likely to have
      triggered the skin eruption are clorazepate dipotassium and theobromine. Their
      interaction with other two constituents such as pseudoephedrine hydrochloride and
      dehydrocholic acid may have caused the adverse reaction by means of a summation
      effect. There are no reports specifically about EM caused by a slimming drug
      preparation and no studies have identified thermogenic pills as cause of EM/EM
      like eruption. Weight-loss compounds in slimming preparations should be kept in
      mind as a possible cause of drug-induced EM-like eruption.

PMID- 23130231
TI  - Primary cutaneous mucinous carcinoma: a rare entity.
AB  - Primary mucinous carcinoma of the skin is a rare adnexal tumor of sweat gland
      origin. A case report is presented of a 70-year-old male, who presented with a
      slow growing mass near the lateral canthus of his left eye. The case was
      clinically diagnosed as a fibroma. An excisional biopsy of the lesion revealed
      mucinous carcinoma of the skin. Investigations excluded the possibility of
      metastatic mucinous carcinoma. Thus, the lesion in the lateral canthus region was
      diagnosed as Primary Mucinous Carcinoma of the skin, a rare site of occurrence.

PMID- 23130232
TI  - Multicentric reticulohistiocytosis.
AB  - Multicentric reticulohistiocytosis is a rare systemic granulomatous disease of an
      unknown cause, characterized by distinct histopathology. The skin, mucosa,
      synovial, bone, and internal organs may be involved. Cutaneous nodules and
      distinctive arthritis are the most prominent clinical features. A 55-year-old
      female was referred from Orthopedic Outpatient Department, with multiple, painful
      and tender nodules on the dorsum of her hands, forearms, elbows, back, and neck.
      The lesions were present predominantly around the joints with associated
      arthropathies. Smaller nodules were seen on the ear helices. There was no other
      clinically evident or investigative abnormality. A histopathological study
      confirmed the diagnosis of multicentric reticulohistiocytosis.

PMID- 23130233
TI  - An unusual case of dapsone syndrome.
AB  - Dapsone, a potent antiparasitic and anti-inflammatory compound, is mainly used in
      the treatment of leprosy and a variety of blistering skin diseases. It may cause
      a severe adverse drug reaction with multiorgan involvement known as dapsone
      hypersensitivity syndrome. We report an unusual case of dapsone hypersensitivity,
      manifesting as bone marrow suppression and peripheral pancytopenia in addition to
      fever, rash, and hepatosplenomegaly.

PMID- 23130234
TI  - Extra ocular sebaceous carcinoma: A rare case report.
AB  - Extra ocular Sebaceous Carcinoma is a rare malignancy when compared to Peri
      ocular variant and these are derived from sebaceous gland epithelium. The
      aggressive types of extra ocular sebaceous neoplasm are reported with lymph node
      and visceral metastasis associated with poor prognosis. Here we report a case of
      extensive cutaneous extra ocular sebaceous cell carcinoma confined to large area
      of scalp proven by Immunohistochemistry without intra cranial involvement,
      distant metastases or evidence of Muir-Torre syndrome.

PMID- 23130235
TI  - Coexistence of porokeratosis of Mibelli with Gardner's syndrome: A rare case
      report.
AB  - Porokeratosis represents a heterogeneous group of disorders characterized
      clinically by a distinctive ridge-like border and histologically by cornoid
      lamellae. Gardner's syndrome, a variant of familial adenomatous polyposis (FAP),
      is an autosomal dominant disease characterized by colorectal polyps, osteomas,
      epidermoid cysts and soft tissue tumors. Here we report a case of 18 yr old
      female who presented with porokeratosis of Mibelli with osteoma, multiple
      epidermoid cytsts, and solitary rectal polyp.

PMID- 23130236
TI  - Parthenium dermatitis manifesting clinically as polymorphic light eruption and
      prurigo nodularis- like lesions with vasculitis-like picture on histopathology.
AB  - Parthenium dermatitis is a widespread and distressing dermatoses in rural and
      urban India caused by the air borne allergen of the Compositae weed Parthenium
      hysterophorus. Parthenium dermatitis has been thought to be mediated solely by
      type IV hypersensitivity, but recently a combined immediate (type I) and delayed
      (type IV) hypersensitivity mechanism has been postulated in the initiation and
      perpetuation of parthenium dermatitis, especially in sensitized subjects with an
      atopic diathesis. Initially, the exposed sites of the body are involved. Later in
      the course of the disease, unexposed sites may get involved. Various clinical
      presentations have been described in parthenium dermatitis. Typically, it
      presents as an air borne contact dermatitis (ABCD) involving the eyelids and
      nasolabial folds Other presentations include a photodermatitis (essentially a
      pseudo photodermatitis), atopic dermatitis, seborrheic dermatitis, exfoliative
      dermatitis, hand dermatitis. Photosensitive lichenoid dermatitis and prurigo
      nodularis are rarer presentations. Uncommon presentations have been described in
      parthenium dermatitis. They include prurigo nodularis-like lesions and
      photosensitive lichenoid eruption. Three cases are presented, two of whom
      presented as polymorphic-like lesions and one as prurigo nodularis. All three
      patch tested positive to parthenium on Day 2. Prick testing was positive in two
      of the three patients. Parthenium dermatitis mimicking polymorphic light eruption
      has not been reported. Histopathology revealed vasculitis in the lesional skin in
      two of the patients. Although leukocytoclastic vasculitis has been reported
      earlier from the prick-tested site, this is the first report demonstrating the
      presence of vasculitis in lesional skin of parthenium dermatitis.

PMID- 23130237
TI  - Idiopathic eruptive macular pigmentation with papillomatosis.
AB  - We present a case of an otherwise healthy 10-year-old girl who presented with
      asymptomatic brown macules over the trunk and proximal extremities, of three
      months' duration. The cutaneous examination revealed multiple, dark brown,
      discrete, round to oval macules and a few mildly elevated lesions over the trunk
      and proximal limbs. The individual lesion was 1-3 cm in diameter and a few showed
      velvety appearance over the surface. Darier's sign was negative. The
      histopathological study from the velvety lesion showed acanthosis, papillomatosis
      and increased melanin in the basal layer. The upper dermis showed sparse
      perivascular infiltrate of lymphocytes without any dermal melanophages. It
      fulfilled the criteria for idiopathic eruptive macular pigmentation with
      additional histological finding of papillomatosis.

PMID- 23130238
TI  - An unusual case of eruptive syringomas presenting as itchy symmetrical lesions on
      both forearms in a patient of hyperkeratotic eczema.
AB  - This report describes an unusual case of bilaterally symmetrically occurring
      hyperpigmented itchy popular lesions on both forearms of a 50-year-old woman. The
      woman had antecedent hyperkeratotic eczema of the feet and she had a similar
      eruption in the past which had cleared with topical steroid application. Biopsy
      of the lesion showed syringomas. We present this case to highlight an unusual
      case of bilaterally symmetrical papular pruritic eruption against a background of
      hyperkeratotic eczema. Some syringomas are supposed to be a response to an
      inflammatory trigger and we wonder if in this case the eczema acted as an
      inflammatory trigger.

PMID- 23130239
TI  - Scrape or Perish: The importance of skin scraping in erythroderma.

PMID- 23130240
TI  - Incidental Hailey-Hailey like acantholysis in a lesion of borderline tuberculoid
      leprosy.

PMID- 23130242
TI  - Fumarates in dermatology.

PMID- 23130241
TI  - Fumaric acid esters in dermatology.
AB  - Fumaric acid esters (FAE) are substances of interest in dermatology. FAE exert
      various activities on cutaneous cells and cytokine networks. So far only a
      mixture of dimethylfumarate (DMF) and three salts of monoethylfumarate (MEF) have
      gained approval for the oral treatment of moderate-to-severe plaque-type
      psoriasis in Germany. DMF seems to be the major active component. There is
      evidence that FAE are not only effective and safe in psoriasis but granulomatous
      non-infectious diseases like granuloma annulare, necrobiosis lipoidica and
      sarcoidosis. In vitro and animal studies suggest some activity in malignant
      melanoma as well.

PMID- 23130243
TI  - Treatment of keratoacanthoma centrifugum marginatum with topical tretinoin.

PMID- 23130244
TI  - Ciprofloxacin induced pyoderma gangrenosum.

PMID- 23130245
TI  - Extensive verrucous seborrheic keratosis mimicking deep mycoses.

PMID- 23130246
TI  - Atrophoderma of pasini and pierini.

PMID- 23130247
TI  - SkIndia Quiz 3 Scalp swelling in a middle-aged woman.

PMID- 23130248
TI  - SkIndia Quiz 4 Asymptomatic sessile skin colored nodule over columella of nose.

PMID- 23130249
TI  - Collodion baby.

PMID- 23130250
TI  - Editorial.

PMID- 23130251
TI  - Mantoux test and its interpretation.
AB  - The tuberculin skin test is one of the few investigations dating from the 19(th)
      century that are still widely used as an important test for diagnosing
      tuberculosis. Though very commonly used by physicians worldwide its
      interpretation always remains difficult and controversial. Various factors like
      age, immunological status coexisting illness etc influence its outcome, so also
      its interpretation. Utmost care is required while interpreting the result and
      giving an opinion. This article has been written with the purpose of elucidating
      the performance and interpretation of the standard tuberculin test.

PMID- 23130252
TI  - Pyoderma gangrenosum: An update.
AB  - Pyoderma gangrenosum (PG) is an uncommon, distinctive cutaneous ulceration which
      is usually idiopathic, but may be associated with many systemic disorders. The
      etipathogenesis of of PG is still not well understood. Clinically it is
      classified into ulcerative, pustular, bullous and vegetative types. A few
      atypical and rare variants have also been described. The diagnosis mainly depends
      on the recognition of evolving clinical features as investigations only assist in
      the diagnosis. In view of this a few criteria have been proposed for the
      diagnosis of PG. the treatment mainly consists of corticosteroids and
      immunosuppressive agents. A few new agents have also been tried in the
      management.

PMID- 23130253
TI  - Endothelin-1 in systemic sclerosis.
AB  - INTRODUCTION: Scleroderma is a systemic disorder with unknown etiology most
      notably characterized by skin thickening and organ damage. Endothelin-1 (ET-1)
      plays a role in skin fibrosis. The aim of this study was survey and comparison of
      ET-1 level in Systemic Sclerosis (SSc) patients with and without digital ulcer.
      MATERIAL AND METHODS: A cross-sectional analytical study conducted among the 95
      patients with scleroderma in 2006 who were referred to the Rheumatology clinic in
      Shariati hospital of Tehran. The questionnaire was completed for every patient.
      Plasma level of endothelin-1 was also measured in all of them. The data was
      analyzed using SPSS software and statistical tests. RESULTS: The result
      indicated, relationship among digital ulcers and digital pitting scars with
      plasma level of ET-1 were significant (P value < 0.05). We could not find any
      significant relationship between age and plasma level of ET-1. CONCLUSION: These
      data indicate plasma level of ET-1 in scleroderma patients with digital ulcer was
      higher than patients without digital ulcer. Thus, increase in plasma level of ET
      1 could be effective in vascular damage, fibrosis, and skin thickness.

PMID- 23130254
TI  - Clinicoepidemiological study of pigmented purpuric dermatoses.
AB  - BACKGROUND: Pigmented purpuric dermatoses (PPD) are a group of vascular disorders
      with varied manifestations which cause concern and are resistant to treatment.
      The literature is still lacking in clinicoepidemiological studies. AIM: To study
      the epidemiology, etiological, host and environmental factors, clinical
      manifestations, its variations, and the type prevalent in this part of the world.
      MATERIALS AND METHODS: All cases of PPD were selected for the study from Skin and
      Venereal Disease, Out Patient Department between January 2008 and June 2009.
      Their history, examination, hematological investigations, and, in a few,
      histopathology findings were also recorded and data obtained were evaluated
      statistically. RESULTS: There were 100 cases of PPD of total 55 323 patients
      (0.18%). There were 79 males and 21 females between 11 and 66 years. They were
      working as police men, security guards, barber, chemist, teachers, students,
      farmers, businessmen, and housewives. In a majority, there was a history of
      prolonged standing in day-to-day work. Purpuric, brownish pigmented, lichenoid or
      atrophic lesions were seen depending upon the type of PPD on lower parts of one
      or both lower limbs. Blood investigations were normal. Schamberg's disease was
      seen in ninety five, Lichen aureus in three, lichenoid dermatosis and Majocchi's
      disease in one case each. DISCUSSION: Three clinical types of PPD were diagnosed
      which may represent different features of the same disease. Cell-mediated
      immunity, immune complexes, capillary fragility, gravitational forces, venous
      hypertension, focal infection, clothing, contact allergy to dyes, and drug intake
      have been incriminating factors in the past. Patient's occupation and
      environmental factors may also be considered contributory in precipitating the
      disease. CONCLUSIONS: The study revealed the problem of PPD in this geographical
      area, its magnitude, clinical presentation, the type prevalent, and possible
      aggravating factors to be kept in mind while managing the disease.

PMID- 23130255
TI  - Cutaneous polyarteritis nodosa: A rare isolated cutaneous vasculitis.
AB  - Cutaneous polyarteritis nodosa (CPAN) is a rare form of cutaneous vasculitis that
      involves small and medium sized arteries of the dermis and subcutaneous tissue
      without systemic involvement. It presents with tender subcutaneous nodules,
      digital gangrene, livedo reticularis and subcutaneous ulcerations. The diagnosis
      is by skin biopsy and characteristic pathologic feature is a leukocytoclastic
      vasculitis in the small to medium-sized arterioles of the dermis. We report a
      rare case of benign cutaneous PAN in a 14-year-old girl who presented with
      history of fever, subcutaneous nodules with cutaneous ulcer and digital gangrene.
      The skin biopsy showed leukocytoclastic vasculitis with fibrinoid necrosis in the
      dermal vessels. She received treatment with steroids and lesions resolved
      completely over a period of month.

PMID- 23130256
TI  - Lipoid proteinosis in a six-year-old child.
AB  - Lipoid proteinosis (LiP) (OMIM 247100) is a rare autosomal recessive disease
      caused by loss of function mutations in the extracellular matrix protein 1 gene,
      ECM1, on chromosome 1q21. Clinically characterized by hoarseness in early
      infancy, followed by waxy papules and plaques on the face and body along with pox
      like and acneiform scars. We report here a 6-year-old female child with LiP, who
      presented to our OPD for recurrent vesicullobullous lesions and beaded lesions
      over eyelid margins.

PMID- 23130258
TI  - Herpes zoster duplex bilateralis in an immunocompetent host.
AB  - Varicella zoster virus causes both chicken pox and herpes zoster. The phenomenon
      of herpes zoster occurring concurrently in two non-contiguous dermatomes
      involving different halves of the body is termed herpes zoster duplex bilateralis
      (HZDB). Few cases, reported in the literature, were seen in either an
      immunosuppressed host or in the older age group. Here we present a case of HZDB
      in an immunocompetent host, probably the first in India.

PMID- 23130257
TI  - Co-occurrence of intraoral hemangioma and port wine stain: A rare case.
AB  - Hemangiomas are neoplastic proliferations of endothelial cells, characterized by
      a period of growth after birth, and eventual spontaneous involution. The course
      can be uneventful with spontaneous resolution; or it may be marked by
      complications such as infection, bleeding, ulceration, visual defects and feeding
      difficulties. Apart from these, rare life-threatening complications such as
      congestive heart failure and consumption coagulopathy may also be seen. Although
      hemangiomas commonly occur in the head and neck region, intraoral occurrence is
      relatively rare. A port wine stain is defined as a macular telangiectatic patch
      which is present at birth and remains throughout life. They may be localized or
      extensive, affecting a whole limb. This article reports a rare case of co
      occurrence of port wine stain with intraoral hemangioma.

PMID- 23130259
TI  - Giant lupus vulgaris: A rare presentation.
AB  - Cutaneous tuberculosis continues to be an important public health problem even
      with the availability of highly effective anti-tuberculous drugs. It constitutes
      0.1% of all cases of extrapulmonary tuberculosis. Lupus vulgaris is the most
      common form of cutaneous tuberculosis that occurs in previously sensitized
      individuals with a moderate degree of immunity against tubercle bacilli. The
      different types of lupus vulgaris include plaque, ulcerative, vegetative, papular
      and nodular, and tumor forms. A 40-year-old man presented with large multiple
      plaques over right upper limb, right side of chest and back, and right lower limb
      for the past 30 years. Histopathology showed numerous noncaseating granulomas
      with Langhan's type of giant cells. The Mantoux test showed strong positivity and
      there was excellent response to anti-tuberculous treatment. This case is being
      reported because of its extreme chronicity of 30 years duration, unusually large
      size and multiplicity of lesions.

PMID- 23130260
TI  - Implantation dermoid of the palm: An unusual presentation.
AB  - An unusual case of palmar implantation dermoid causing paresthesia in the fingers
      is reported. The tumor was successfully excised with relief of the symptoms. The
      report discusses important points regarding management of such tumors.

PMID- 23130261
TI  - Cutaneous angiomyolipoma.
AB  - We report a case of cutaneous angiomyolipoma (AML) found on the anterior
      abdominal wall of a 3-year-old female child. Histologic examination showed a well
      circumscribed nodule in the dermis composed of an intimate mixture of convoluted
      thick-walled blood vessels, smooth muscle, and mature fat. This lesion differs
      from renal AML in terms of a lack of association with tuberous sclerosis,
      circumscription, absence of epithelioid cells, and male predominance. We
      concluded that the unique features of this lesion distinguish it from other
      lesions such as angiomyoma, angiolipoma, myolipoma, haemangioma, and other mixed
      mesenchymal tumors. This case report suggests that the features considered
      diagnostic of AML can occur in extrarenal sites and, therefore, this diagnosis
      cannot be excluded on the basis of site alone.

PMID- 23130262
TI  - Recalcitrant generalized pustular eruption after diltiazem.
AB  - Generalized pustular eruptions may occasionally present challenges both for
      diagnosis and treatment. A 55-year-old male was hospitalized with fever and a
      severe generalized pustular eruption after recent intake of diltiazem. A careful
      interpretation of history, clinical course and investigation findings and an
      active treatment intervention proved the key to management of the case.

PMID- 23130263
TI  - Annular, erythematous skin lesions in a neonate.
AB  - A 7-day-old premature female infant presented with rapidly progressive,
      erythematous, annular skin lesions from the 5(th) day of life. She was diagnosed
      provisionally as a case of neonatal lupus erythematosus and was investigated
      accordingly. Histopathological examination of the skin biopsy specimen revealed
      presence of hyphae of dermatophytes in the stratum corneum, and the diagnosis was
      changed to tinea corporis. Differential diagnosis of the annular erythema of
      infancy has been discussed and the importance of scraping a scaly lesion for KOH
      preparation in the diagnostic work-up of such a patient has been highlighted.

PMID- 23130264
TI  - Keratitis-Ichthyosis-Deafness syndrome: A rare congenital disorder.
AB  - Keratitis-Icthyosis-Deafness syndrome is a rare congenital disorder characterized
      by keratitis, ichthyosis, and deafness. We report a 13 year old female child who
      presented with diffuse alopecia of the scalp and body. There was
      erythrokeratoderma of face and discrete hyperkeratotic hyperpigmented papulo
      plaque lesions on the body. Patient also had reticulate hyperkeratosis of palms
      and soles. There was history of recurrent episodes of folliculitis over the scalp
      and body. There was no evidence of any malignancy. Eye involvement in the form of
      bilateral vascularising keratitis was present. There was bilateral mixed hearing
      loss.

PMID- 23130265
TI  - Neurofibromatosis-1 with bilateral partial radial artery stenosis.
AB  - Not much attention is paid to vascular complications in neurofibromatosis-1 (NF
      1) though they are well known to occur. A case of vascular NF-1 with bilateral
      partial radial artery stenosis resulting in digital gangrene involving fingers of
      both hands is being reported here. Various vascular abnormalities in NF-1 as
      complications resulting from them and their management is briefly highlighted.

PMID- 23130266
TI  - Progressive symmetric erythrokeratodermia with delayed intellectual milestones
      and convulsions.
AB  - Progressive symmetric erythrokeratoderma is an uncommon genodermatosis and is
      thought to arise due to mutations in the connexin gene, however, genetic
      heterogenicity has been described. Very few cases of neurological involvement
      have been described in this unusual entity. We report a case of progressive
      symmetric erythrokeratoderma, with convulsions and delayed intellectual
      milestones.

PMID- 23130267
TI  - Transporting preloaded chambers for patch testing.

PMID- 23130268
TI  - 'Venetian blinds' artifact in dermatohistopathology.
AB  - The 'Venetian blinds' artifact is an uncommon tissue cutting artifact that leads
      to the formation of parallel series of strips of tissue separated from one
      another by narrow clear spaces. It has been attributed to either hardening of the
      tissue in the paraffin block or defective assembly of the microtome knife. This
      artifact occurs in both inflammatory and neoplastic conditions in which there are
      nodular collections of cells and may reflect vibration-induced disintegration of
      fragile cellular aggregates that lack dermal stromal support. At scanning
      magnification, it serves to draw the histopathologist's eye to the site of
      pathology.

PMID- 23130269
TI  - Finasteride and sexual side effects.
AB  - Finasteride, a 5-alpha reductase inhibitor, widely used in the medical management
      of male pattern hairloss, has been reported to cause sexual side effects. This
      article critically examines the evidence available and makes recommendations as
      to how a physician should counsel a patient while prescribing the drug.

PMID- 23130270
TI  - Aortoarteritis with systemic lupus erythematosus and secondary antiphopholipid
      syndrome.

PMID- 23130271
TI  - Histoid leprosy with penile shaft lesions.

PMID- 23130272
TI  - Cutis laxa with pulmonary artery stenosis.

PMID- 23130273
TI  - Linear psoriasis: A rare presentation.

PMID- 23130274
TI  - Fire-breathing burn.

PMID- 23130275
TI  - Generalized papular granuloma annulare.

PMID- 23130276
TI  - Recurrence of zosteriform lesions on the contralateral dermatome: A diagnostic
      dilemma.

PMID- 23130277
TI  - SkIndia Quiz 5: Shiny, waxy papules on face and extremities in a female with
      dyspnea.

PMID- 23130278
TI  - Angiolymphoid hyperplasia with eosinophilia.

PMID- 23130279
TI  - On the clinical significance of cutaneous melanoma's precursors.
AB  - WE CAN IDENTIFY THREE MAIN GROUPS OF CUTANEOUS PIGMENTED LESIONS THAT COULD BE
      REPRESENTED AS MELANOMA PRECURSORS: (a) congenital melanocytic nevi, (b)
      dysplastic or atypical nevi, and (c) acquired melanocytic nevi. The occurrence of
      melanoma in small and intermediate congenital melanocytic nevi is very uncommon,
      but there is a high risk in large congenital melanocytic nevi, in particular
      those arising in the so-called "bathing trunk" distribution. It is very important
      to distinguish the familial dysplastic nevus syndrome, which is a strong risk
      factor for cutaneous melanoma, from not familial (sporadic) dysplastic nevus, in
      which the risk for melanoma would depend on the total number of melanocytic nevi,
      phototype, and on the relationship to environmental factors.

PMID- 23130281
TI  - Oral cavity and leprosy.
AB  - Although leprosy involves the oral cavity in up to 60% of the patients,
      examination of the oral cavity in leprosy clinics or oral health science clinics
      is often neglected. Oral involvement in leprosy can broadly be divided into non
      specific and specific lesions. In this review, we discuss various oral
      manifestations in leprosy patients so as to increase the awareness about this
      aspect among dermatologists and dental surgeons.

PMID- 23130280
TI  - Parthenium the terminator: An update.
AB  - Parthenium dermatitis is a distressing dermatitis caused by the air borne
      allergen of the Compositae weed Parthenium hysterophorus. Uncommon presentations,
      newer insights in pathogenesis and management of this "scourge" are discussed in
      this article.

PMID- 23130282
TI  - Comorbid conditions in psoriasis - Higher frequency in females: A prospective
      study.
AB  - AIM: To study the association of obesity, diabetes, hypertension, and abnormal
      lipid profile in women above 40 years of age with psoriasis. MATERIALS AND
      METHODS: Two hundred consecutive female patients with psoriasis attending private
      clinics were included. Complete general, systemic, and dermatological
      examinations were performed. Blood pressure, blood sugar, and lipid profile were
      recorded in all patients and the findings analyzed. RESULTS: Of 200 patients, 45
      were obese. Eighty-eight patients had diabetes mellitus and 29 had dyslipidemia
      of whom 13 and 18, respectively, were detected at the time of enrolment. All 25
      patients with systemic hypertension were on treatment. A total of 177 (88.5%)
      patients had one or more comorbid conditions. This frequency is much higher when
      compared to other Indian studies where the sample included patients of both
      sexes.

PMID- 23130283
TI  - Comparative study of 15% TCA peel versus 35% glycolic acid peel for the treatment
      of melasma.
AB  - BACKGROUND: Chemical peels are the mainstay of a cosmetic practitioner's
      armamentarium because they can be used to treat some skin disorders and can
      provide aesthetic benefit. OBJECTIVES: To compare 15% TCA peel and 35% glycolic
      acid peel for the treatment of melasma. MATERIAL AND METHODS: We selected 30
      participants of melasma aged between 20 and 50 years from the dermatology
      outpatient department and treated equal numbers with 15% TCA and 35% glycolic
      acid. RESULTS: Subjective response as graded by the patient showed good or very
      good response in 70% participants in the glycolic acid group and 64% in the TCA
      group. CONCLUSIONS: There was statistically insignificant difference in the
      efficacy between the two groups for the treatment of melasma.

PMID- 23130284
TI  - Clinical patterns of vitiligo and its associated co morbidities: A prospective
      controlled cross-sectional study in South India.
AB  - AIM: The purpose of this study is to assess the clinical patterns and
      associations of vitiligo, audiometric functions, and ocular involvement and to
      correlate the morphology, clinical behaviour and comorbidities associated with
      vitiligo. SETTINGS AND DESIGN: For this prospective and cross-sectional study 80
      self-reporting patients in the age group 7-75 years with vitiligo attending the
      outpatient department of Manipal hospital during the period August 2008 to
      February 2010 were selected and the data was analysed. MATERIALS AND METHODS: The
      patients were subjected to detailed history, clinical examination and
      investigations [complete blood count (CBC), absolute eosinophil count (AEC),
      erythrocyte sedimentation rate (ESR), thyroid stimulating hormone (TSH), vitamin
      B12 estimation, fasting blood sugar (FBS), and post prandial blood sugar
      (PPBS),antibody titre estimations that is antithyroid peroxidase (ATPA),
      antithyroglobulin (ATA), antinuclear antibodies (ANA),urine analysis],
      audiometric evaluation and ophthalmic examination. STATISTICAL ANALYSIS USED: The
      Fisher exact test has been used to find the significance of study parameters on
      categorical scale between two or more groups. RESULTS: In the present series of
      80 cases, 41 (51.25%) were males and 39 (48.75%) were females. The male to female
      ratio was 1.05:1. In our study 20% cases gave definite family history of vitiligo
      and patients in the age group of 20 - 30 years were the most commonly affected.
      Generalized vitiligo (31.3%) was the most common type followed by segmental
      (30%), focal (18.8%), acrofacial (8.8%), and mucosal vitiligo (11.3%). In the
      present study there was a high incidence of autoantibodies (22.5%), vitamin B12
      deficiency (30%), hypothyroidism (11.3%), elevated absolute eosinophil count
      (16.3%), hypoacusis (10%) and retinal changes (8.8%). This suggests multisystem
      autoimmunity in vitiligo.

PMID- 23130285
TI  - Coexistence of psoriasis with bullous pemphigoid.
AB  - Psoriasis vulgaris and bullous pemphigoid (BP) represent two clinically well
      characterized, chronic, inflammatory skin conditions. The concomitant occurrence
      of these two entities in a patient is rare. Here we report a 57-year-old male
      suffering from psoriasis vulgaris for 15 years on irregular medication who
      noticed eruption of blisters all over the body. We believe that this is the first
      case report of psoriasis vulgaris coexistent with bullous pemphigoid in Indian
      literature. Please check where you want bullous pemphigoid and where you want
      psoriasis pemphigoides.

PMID- 23130286
TI  - Mycosis Fungoides: Tumour d'emblee.
AB  - Mycosis Fungoides is a Cutaneous T-cell lymphoma characterized by infiltration of
      skin with patches, plaques, and nodules composed of T-lymphocytes. It is the most
      common type of Cutaneous T-Cell Lymphoma and accounts for almost 50% of all
      primary cutaneous lymphoma. Tumour d' emblee is the term used for the patient
      presenting with skin tumors not preceded by patches or plaques. We report a rare
      case of mycosis fungoides d' emblee variant with tumors of only 3 months duration
      without any preceding skin lesions.

PMID- 23130287
TI  - Hypohidrotic ectodermal dysplasia.
AB  - Hypohidrotic ectodermal dysplasia (HED) is a rare genetic disorder characterized
      by the faulty development of the ectodermal structure, resulting in most notably
      anhydrosis/hypohydrosis, hypotrichosis and hypodontia. The condition is usually
      an X-linked recessive disorder affecting predominantly males. We are here
      reporting a classical case of hypohidrotic ectodermal dysplasia with a review of
      the literature.

PMID- 23130288
TI  - Aggressive angiomyxoma of the vulva: An uncommon entity.
AB  - Aggressive angiomyxoma is a rare, locally invasive mesenchymal tumor occurring
      usually in women of reproductive age, which carries a high risk for local
      relapse; hence the need to differentiate it from the other mesenchymal tumors
      occurring in this region. We describe a case of a 44-year-old female presenting
      with a large pedunculated swelling on the right labia majora.

PMID- 23130289
TI  - Pigmented epidermal cyst with dense collection of melanin: A rare entity - Report
      of a case with review of the literature.
AB  - Epidermal cyst is a very common benign cystic lesion of the skin. It is usual to
      find ulceration of the lining epithelium, rupture of the cyst wall with chronic
      inflammation and foreign body giant cell reaction. But, it is very rare to see an
      epidermal cyst with marked accumulation of melanin pigment. Only a few cases of
      pigmented epidermal cyst with dense collection of melanin pigment have been
      published in the literature. Here, we are reporting a case of ruptured epidermal
      cyst with keratin granuloma formation and showing dense collection of melanin
      pigment.

PMID- 23130290
TI  - Disseminated cutaneous cysticercosis and neurocysticercosis: A rare occurrence.
AB  - Disseminated cysticercosis is a parasitic infestation of pork tapeworm, Taenia
      solium. A 19-year-old female presented with multiple nodules all over her body
      since 12 months. Histopathology showed features suggestive of parasitic granuloma
      with multinucleated giant cells and plenty of eosinophils admixed with necrosis.
      Ultrasonography of these lesions showed multiple well-defined cystic lesions of
      varying size with a few specks of calcification. Cranial computed tomography scan
      showed bilateral, multiple, small hyperdense lesions in the supratentorial
      compartment. She was treated with oral albendazole and oral corticosteroids. This
      case is being reported because of its rare, disseminated nature with cutaneous,
      neural and ocular involvement.

PMID- 23130291
TI  - Sebaceous carcinoma of scalp with proliferating trichilemmal cyst.
AB  - Sebaceous carcinoma is a rare neoplasm of the sebaceous gland. It is diagnosed
      mainly on histopathology and, clinically, it may mimic other neoplasms like
      squamous or basal cell carcinoma. We came across a patient presenting with a non
      healing ulcer over the left temporo-parietal region of the scalp since 4 years
      and a single asymptomatic nodule over the occipital region since 3 years.
      Histopathology from an ulcer was pathognomonic of sebaceous carcinoma and that
      from a nodule was suggestive of proliferating trichilemmal cyst. The patient was
      screened for Muir Torre syndrome. We referred the patient to the oncologist for
      further management, where the patient was advised complete excision of the
      lesion.

PMID- 23130292
TI  - Dermatitis artefacta.
AB  - Dermatitis artefacta (DA) is a psychocutaneous disorder where the skin lesions
      are self self-induced to satisfy an unconscious psychological or emotional need.
      We report a case of DA where we video recorded the patient self-inducing the
      lesions.

PMID- 23130293
TI  - Piebaldism: A brief report and review of the literature.
AB  - Piebaldism is a rare autosomal dominant disorder of melanocyte development
      characterized by a congenital white forelock and multiple symmetrical stable
      hypopigmented or depigmented macules. We report a family with piebaldism
      affecting three successive generations and also review the literature.

PMID- 23130294
TI  - Lipoid proteinosis: Histopathological characterization of early papulovesicular
      lesions.

PMID- 23130295
TI  - Copper chloride antiperspirant action.

PMID- 23130296
TI  - Multiple familial trichoepitheliomas in association with squamous cell carcinoma.

PMID- 23130297
TI  - SkIndia Quiz 6 Multiple recurrent erythematous scaly annular plaques in a child.

PMID- 23130298
TI  - Anonychia congenita.

PMID- 23130299
TI  - Vulval Syringoma: First report of a case in an Egyptian female.

PMID- 23130301
TI  - Xenograft Failure of Pulmonary Valved Conduit Cross-linked with Glutaraldehyde or
      Not Cross-linked in a Pig to Goat Implantation Model.
AB  - BACKGROUND: Biologic valved grafts are important in cardiac surgery, and although
      several types of graft are currently available, most commercial xenografts tend
      to cause early disfiguration due to intimal proliferation and calcification. We
      studied the graft failure patterns on non-fixed and glutaraldehyde-fixed
      pulmonary xenograft in vivo animal experiment. MATERIALS AND METHODS: Pulmonary
      valved conduits were obtained from the right ventricular outflow tract of eleven
      miniature pigs. The grafts were subjected to 2 different preservation methods;
      with or without glutaraldehyde fixation: glutaraldehyde fixation (n=7) and non
      glutaraldehyde fixation (n=4). The processed explanted pulmonary valved grafts of
      miniature pig were then transplanted into eleven goats. Calcium quantization was
      achieved in all of the explanted xenograft, hemodynamic, histopathologic and
      radiologic evaluations were performed in the graft which the transplantation
      period was over 300 days (n=7). RESULTS: Grafts treated with glutaraldehyde
      fixation had more calcification and conduit obstruction in mid-term period.
      Calcium deposition also appeared much higher in the glutaraldehyde treated graft
      compared to the non-glutaraldehyde treated graft (p<0.05). CONCLUSION: The
      present study suggests that xenografts prepared using glutaraldehyde fixation
      alone appeared to have severe calcification compared to the findings of non
      glutaraldehyde treated xenografts and to be managed with proper anticalcification
      treatment and novel preservation methods. This experiment gives the useful basic
      chemical, histologic data of xenograft failure model with calcification for
      further animal study.

PMID- 23130300
TI  - Conduits for coronary bypass: vein grafts.
AB  - The saphenous vein has been the principal conduit for coronary bypass grafting
      from the beginning, circa 1970. This report briefly traces this history and
      concomitantly presents one surgeons experience and personal views on use of the
      vein graft. As such it is not exhaustive but meant to be practical with a modest
      number of references. The focus is that of providing guidance and perspective
      which may be at variance with that of others and recognizing that there may be
      many ways to accomplish the task at hand. Hopefully the surgeon in training/early
      career may find this instructive on the journey to surgical maturity.

PMID- 23130302
TI  - Does additional aortic procedure carry a higher risk in patients undergoing
      aortic valve replacement?
AB  - BACKGROUND: With growing attention to the aortopathy associated with aortic valve
      diseases, the number of candidates for accompanying ascending aorta and/or root
      replacement is increasing among the patients who require aortic valve replacement
      (AVR). However, such procedures have been considered more risky than AVR alone.
      This study aimed to compare the surgical outcome of isolated AVR and AVR combined
      with aortic procedures. MATERIALS AND METHODS: A total of 86 patients who
      underwent elective AVR between 2004 and June 2010 were divided into two groups:
      complex AVR (n=50, AVR with ascending aorta replacement in 24 and the Bentall
      procedure in 26) and simple AVR (n=36). Preoperative characteristics, surgical
      data, intra- and postoperative allogenic blood transfusion requirement, the
      postoperative clinical course, and major complications were retrospectively
      reviewed and compared. RESULTS: The preoperative mean logistic European System
      for Cardiac Operative Risk Evaluation (%) did not differ between the groups:
      11.0+/-7.8% in the complex AVR group and 12.3+/-8.0% in the simple AVR group.
      Although complex AVR required longer cardiopulmonary bypass (152.4+/-52.6 minutes
      vs. 109.7+/-22.7 minutes, p=0.001), the quantity of allogenic blood products did
      not differ (13.4+/-14.7 units vs. 13.9+/-11.2 units). There was no mortality,
      mechanical circulatory support, stroke, or renal failure requiring
      hemodialysis/filtration. No difference was found in the incidence of bleeding
      (40% vs. 33.3%) which was defined as red blood cell transfusion >=5 units,
      reoperation, or intentional delayed closure. The incidence of mediastinitis (2.0%
      vs. 0%), ventilator >=24 hours (4.0% vs. 2.8%), atrial fibrillation (18.0% vs.
      25.0%), mean intensive care unit stay (34.5 hours vs. 38.8 hours), and median
      hospital stay (8 days vs. 7 days) did not differ, either. CONCLUSION: AVR
      combined with additional aortic or root replacement showed an excellent outcome
      and recovery course equivalent to that after isolated AVR.

PMID- 23130304
TI  - Long-term Surveillance Comparing Satisfaction between the Early Experience of
      Nuss Procedure vs. Ravitch Procedure.
AB  - BACKGROUND: Long-term surveillance comparing satisfaction between the early
      experience of Nuss procedure vs. Ravitch procedure. MATERIALS AND METHODS: A
      total of 100 patients that underwent surgical correction of a pectus excavatum
      between 2001 and 2004 and were followed for >=2 years were included. Surveillance
      on the degree of satisfaction was performed using five-levels of the Likert scale
      and self-assessment scoring. RESULTS: Nuss or Ravitch surgery was performed in 63
      and 37 patients, respectively. The Nuss procedure required a shorter operation
      time and shorter hospital stay than the Ravitch procedure (p<0.001). The
      surveillance demonstrated that 17.6% of the Nuss group and 35.7% of the Ravitch
      group were not satisfied with the outcome of the surgery (p=0.072). The most
      common causes of dissatisfaction were redepression in the Nuss group (n=5) and
      incomplete correction in the Ravitch group (n=7). The multivariate analysis
      showed that reoperation and a high postoperative pectus index were significant
      risk factors for a low satisfaction score. CONCLUSION: The Nuss procedure had
      several advantages over the Ravitch procedure in the immediate postoperative
      period. However, the long-term satisfaction was determined by a complete
      correction without recurrence or need for re-intervention rather than by the
      operation type.

PMID- 23130303
TI  - Risk Factors of Red Blood Cell Transfusion in Isolate off Pump Coronary Artery
      Bypass Surgery.
AB  - BACKGROUND: Perioperative transfusion of red blood cell (RBC) may cause adverse
      effects. Bloodless-cardiac surgery has been spotlighted to avoid those problems.
      Off pump coronary artery bypass (OPCAB) surgery can decrease the transfusion.
      However, the risk factors of transfusions in OPCAB have not been investigated
      properly. MATERIALS AND METHODS: One hundred and thirteen patients
      (male:female=35:78, mean age=66.7+/-9.9 years) who received isolated OPCAB were
      retrospectively analyzed from March 2006 to September 2007. The threshold of RBC
      transfusion was 28.0% of hematocrit. Bilateral internal thoracic arteries graft
      were used for 99 patients (87.6%). One hundred and three (91.1%) and 35 patients
      (31.5%) took aspirin and clopidogrel just before surgery. RESULTS: Sixty-five
      patients (47.5%) received the RBC transfusion (mean 2.2+/-3.2 units). Mortality
      and major complications were not different between transfusion and no-transfusion
      group. But, ventilator support time, intensive care unit stay and hospitalization
      period had been reduced in no-transfusion group (p<0.05). In multivariate
      analysis, patients risk factors for RBC transfusion were preoperative low
      hematocrit (<37.5%) and clopidogrel medication. Surgical risk factors were longer
      graft harvesting time (>75 minutes) and total operation time (>5.5 hours,
      p<0.05). CONCLUSION: We performed the transfusion according to transfusion
      guideline; over 40% cases could conduct the OPCAB without transfusion. There were
      no differences in major clinical results between transfusion and non-transfusion
      group. In addition, when used together with accurate understanding of transfusion
      risk factors, it is expected to increase the proportion of patients that do not
      undergo transfusions.

PMID- 23130305
TI  - The Effect of Thoracoscopic Pleurodesis in Primary Spontaneous Pneumothorax:
      Apical Parietal Pleurectomy versus Pleural Abrasion.
AB  - BACKGROUND: The standard operative treatment of primary spontaneous pneumothorax
      (PSP) is thoracoscopic wedge resection, but necessity of pleurodesis still
      remains controversial. Nevertheless, pleural procedure after wedge resection such
      as pleurodesis has been performed in some patients who need an extremely low
      recurrence rate. MATERIALS AND METHODS: From January 2000 to July 2010, 207
      patients who had undergone thoracoscopic wedge resection and pleurodesis were
      enrolled in this study. All patients were divided into two groups according to
      the methods of pleurodesis; apical parietal pleurectomy (group A) and pleural
      abrasion (group B). The recurrence after surgery had been checked by reviewing
      medical record through follow-up in ambulatory care clinic or calling to the
      patients, directly until January 2011. RESULTS: Of the 207 patients, the
      recurrence rate of group A and B was 9.1% and 12.8%, respectively and there was a
      significant difference (p=0.01, Cox's proportional hazard model). There was no
      significant difference in age, gender, smoking status, and body mass index
      between two groups. CONCLUSION: This study suggests that the risk of recurrence
      after surgery in PSP is significantly low in patients who underwent thoracoscopic
      wedge resection with parietal pleurectomy than pleural abrasion.

PMID- 23130306
TI  - Emergent surgical intervention for embolization of atrial septal defect closure
      device.
AB  - The percutaneous transcatheter closure of secundum atrial septal defect has
      recently become an increasingly widespread alternative to surgical closure in
      many centers. Although immediate, short, and intermediate term results of
      percutaneous transcatheter septal closure are promising, the procedure is not
      free from inherent complications that could be lethal. We report a case of device
      embolization necessitating emergent surgical retrieval.

PMID- 23130307
TI  - Successful management of pulmonary and inferior vena cava tumor embolism from
      renal cell carcinoma.
AB  - Pulmonary tumor embolism can be a cause of respiratory failure in patients with
      cancer even though it occurs rarely. We describe a 56-year-old man who underwent
      a pulmonary tumor embolectomy using cardiopulmonary bypass on beating heart
      combined with inferior vena cava embolectomy and right radical nephrectomy.
      Aggressive surgical treatment in this severe case is necessary not only to reduce
      the fatal outcome of pulmonary embolism in the short run, but also to improve the
      oncological prognosis in the long term.

PMID- 23130308
TI  - Transcatheter Embolization of Giant Pulmonary Arteriovenous Malformation with an
      Amplatzer Vascular Plug II.
AB  - Pulmonary arteriovenous malformation (PAVM) is a rare anomalous direct
      communication between the pulmonary artery and vein with a considerable risk of
      serious complications such as cerebral thromboembolism or abscess and pulmonary
      hemorrhage. Although the past, surgical resection such as lobectomy was mostly
      used to treat PAVM, the recent development of endovascular treatment has made it
      a primary consideration to perform transcatheter embolization using coils or
      detachable balloons. We report a case of successful transcatheter embolization of
      giant PAVM with the second generation Amplatzer vascular plug II as a new self
      expanding device.

PMID- 23130309
TI  - Double primary aortoenteric fistulae: a case report of two simultaneous primary
      aortoenteric fistulae in one patient.
AB  - Aortoenteric fistula is a rare but potentially fatal condition causing massive
      gastrointestinal bleeding. In particular, double primary aortoenteric fistulae
      are vanishingly rare. We encountered a 75-year-old male patient suffering from
      abdominal pain, hematochezia, hematemesis, and hypotension. His computed
      tomography images showed abdominal aortic aneurysm and suspected aortoenteric
      fistulae. During surgery, we found two primary aortoenteric fistulae. The one
      fistula was detected between the abdominal aorta and the third portion of the
      duodenum, and the other fistula was detected between the abdominal aorta and the
      sigmoid colon. We conducted the closure of the fistulae, the exclusion of the
      aneurysm, and axillo-bifemoral bypass with a polytetrafluoroethylene graft. The
      patient was discharged with no complications on the 21st postoperative day.

PMID- 23130310
TI  - Application of percutaneous cardiopulmonary support for cardiac tamponade
      following blunt chest trauma: two case reports.
AB  - Since the advent of percutaneous cardiopulmonary support (PCPS), its application
      has been extended to massively injured patient. Cardiac injury following blunt
      chest trauma brings out high mortality and morbidity. In our cases, patients had
      high injury severity score by blunt trauma and presented sudden hemodynamic
      collapse in emergency room. We quickly detected cardiac tamponade by focused
      assessment with sonography for trauma and implemented PCPS. As PCPS established,
      their vital sign restored and then, they were transferred to the operation room
      (OR) securely. After all injured lesion repaired, PCPS weaned successfully in OR.
      They were discharged without complication on day 26 and 55, retrospectively.

PMID- 23130311
TI  - Complete Vascular Ring Caused by Kommerell's Diverticulum and Right Aortic Arch
      with Mirror Image Branching.
AB  - Vascular ring, caused by Kommerell's diverticulum and ligamentum arteriosum, in a
      patient with right aortic arch and mirror image branching is extremely rare. A 10
      month-old boy with coughing and stridor was diagnosed as having tracheo
      esophageal stenosis, which is caused by a vascular ring with Kommerell's
      diverticulum, ligamentum arteriosum, right aortic arch, and mirror image
      branching. Kommerell's diverticulum was successfully resected via a left
      thoracotomy. The patient has been free from tracheo-esophageal stenosis for a
      year after the surgery.

PMID- 23130312
TI  - Treatment of complete persistent sciatic artery with distal thromboembolism by
      thromboembolectomy only.
AB  - A persistent sciatic artery (PSA) is very rare congenital vascular anomaly which
      is present in 0.025% to 0.04% of the population by an angiographic study. A PSA
      is usually combined with aneurismal disease or thromboembolic events because of
      its arteriosclerosis and vessel wall degeneration. The treatments of symptomatic
      PSA are comprised of exclusion of PSA from circulation and bypass surgery for the
      lower limb. However, surgical treatment should be tailored to its anatomy and
      presentation. We report a successful treatment of PSA with distal thromboembolism
      by thromboembolectomy without bypass surgery.

PMID- 23130313
TI  - Successful management of a recurrent primary malignant fibrous histiocytoma of
      the lung: report of a case.
AB  - We describe herein an extremely rare case of a recurrent primary pulmonary
      malignant fibrous histiocytoma 3 months after operation that occurred in a 55
      year-old man who was treated with chemotherapy and radiotherapy successfully.
      Until now, 36 months later, the patient has shown no evidence of tumor
      recurrence. The clinical, radiographic, and pathologic features are reported here
      together with a brief review of the literature.

PMID- 23130314
TI  - An Adult Right-sided Bochdalek Hernia Accompanied with Hepatic Hypoplasia and
      Inguinal Hernia.
AB  - We herein report a very rare case of adult right-sided Bochdalek hernia
      accompanied with hepatic hypoplasia and inguinal hernia. A 29-year-old man was
      admitted with right-sided pneumothorax. A computed tomography was performed and
      revealed large right sided Bochdalek hernia with hepatic hypoplasia. Under
      thoracolaparotomy, the defect was closed with Gore-Tex soft tissue patch. After
      the operation, left-sided inguinal hernia was found. However, it turned out that
      it had been present during infancy and spontaneously resolved during adolescence.
      This is the first report of right-sided Bochdalek hernia with hepatic hypoplasia
      and inguinal hernia in an adult.

PMID- 23130315
TI  - Clinical relevance of adipokines.
AB  - The incidence of obesity has increased dramatically during recent decades.
      Obesity increases the risk for metabolic and cardiovascular diseases and may
      therefore contribute to premature death. With increasing fat mass, secretion of
      adipose tissue derived bioactive molecules (adipokines) changes towards a pro
      inflammatory, diabetogenic and atherogenic pattern. Adipokines are involved in
      the regulation of appetite and satiety, energy expenditure, activity, endothelial
      function, hemostasis, blood pressure, insulin sensitivity, energy metabolism in
      insulin sensitive tissues, adipogenesis, fat distribution and insulin secretion
      in pancreatic beta-cells. Therefore, adipokines are clinically relevant as
      biomarkers for fat distribution, adipose tissue function, liver fat content,
      insulin sensitivity, chronic inflammation and have the potential for future
      pharmacological treatment strategies for obesity and its related diseases. This
      review focuses on the clinical relevance of selected adipokines as markers or
      predictors of obesity related diseases and as potential therapeutic tools or
      targets in metabolic and cardiovascular diseases.

PMID- 23130316
TI  - Transcriptional regulation of pyruvate dehydrogenase kinase.
AB  - The pyruvate dehydrogenase complex (PDC) activity is crucial to maintains blood
      glucose and ATP levels, which largely depends on the phosphorylation status by
      pyruvate dehydrogenase kinase (PDK) isoenzymes. Although it has been reported
      that PDC is phosphorylated and inactivated by PDK2 and PDK4 in metabolically
      active tissues including liver, skeletal muscle, heart, and kidney during
      starvation and diabetes, the precise mechanisms by which expression of PDK2 and
      PDK4 are transcriptionally regulated still remains unclear. Insulin represses the
      expression of PDK2 and PDK4 via phosphorylation of FOXO through PI3K/Akt
      signaling pathway. Several nuclear hormone receptors activated due to fasting or
      increased fat supply, including peroxisome proliferator-activated receptors,
      glucocorticoid receptors, estrogen-related receptors, and thyroid hormone
      receptors, also participate in the up-regulation of PDK2 and PDK4; however, the
      endogenous ligands that bind those nuclear receptors have not been identified. It
      has been recently suggested that growth hormone, adiponectin, epinephrine, and
      rosiglitazone also control the expression of PDK4 in tissue-specific manners. In
      this review, we discuss several factors involved in the expressional regulation
      of PDK2 and PDK4, and introduce current studies aimed at providing a better
      understanding of the molecular mechanisms that underlie the development of
      metabolic diseases such as diabetes.

PMID- 23130317
TI  - Management of type 2 diabetes mellitus in older adults.
AB  - In the near future, the majority of patients with diabetes will be adults aged 65
      or older. Unlike young adults with diabetes, elderly diabetic people may be
      affected by a variety of comorbid conditions such as depression, cognitive
      impairment, muscle weakness (sarcopenia), falls and fractures, and physical
      frailty. These geriatric syndromes should be considered in the establishment of
      treatment goals in older adults with diabetes. Although there are several
      guidelines for the management of diabetes, only a few are specifically designed
      for the elderly with diabetes. In this review, we present specific conditions of
      elderly diabetes which should be taken into account in the management of diabetes
      in older adults. We also present advantages and disadvantages of various glucose
      lowering agents that should be considered when choosing a proper regimen for
      older adults with diabetes.

PMID- 23130318
TI  - C-Peptide and vascular complications in type 2 diabetic subjects.

PMID- 23130319
TI  - The association of self-reported coronary heart disease with diabetes duration in
      Korea.
AB  - BACKGROUND: This study aimed to investigate the association of diabetes duration
      with self-reported coronary heart disease (CHD) in Korea. METHODS: Among data
      from 34,145 persons compiled in the third Korean National Health and Nutrition
      Examination Survey in 2005, laboratory test and nutritional survey data from
      5,531 persons were examined. The participants were asked to recall a physician's
      diagnosis of CHD (angina or myocardial infarction). RESULTS: Age- and sex
      adjusted relative risk for CHD was 1.51 (95% confidence interval [CI], 0.64 to
      3.59; not significant) for diabetes with duration of <1 year, 2.27 (95% CI, 1.14
      to 4.54; P=0.020) for diabetes with a duration of 1 to 5 years, and 3.29 (95% CI,
      1.78 to 6.08; P<0.001) for diabetes with a duration >5 years, compared with non
      diabetes as a control. Even after adjusting for age, sex, current smoking status,
      waist circumference, hypertension, triglycerides, high density lipoprotein
      cholesterol, and fasting plasma glucose, relative risk for CHD was 2.87 (95% CI,
      1.01 to 8.11; P=0.047) in diabetes with a duration of 6 to 10 years and 4.07 (95%
      CI, 1.73 to 9.63; P=0.001) in diabetes with duration of >10 years with non
      diabetes as a control. CONCLUSION: CHD prevalence increased with an increase in
      diabetes duration in Korean men and women. Recently detected diabetes (duration
      <1 year) was not significantly associated with CHD prevalence compared to non
      diabetes. However, diabetes of a duration of >5 years was associated with an
      increase in CHD compared to non-diabetics after adjusting for several CHD risk
      factors.

PMID- 23130320
TI  - Cardio-metabolic features of type 2 diabetes subjects discordant in the diagnosis
      of metabolic syndrome.
AB  - BACKGROUND: The aim of this study is to investigate the cardio-metabolic
      parameters and surrogate markers of insulin resistance in a discordant group of
      type 2 diabetes (T2DM) subjects who satisfy the Adults Treatment Panel (ATP) III
      criteria, but not the International Diabetes Federation (IDF) criteria, for
      metabolic syndrome (MetS). METHODS: We assessed the prevalence of MetS in T2DM
      subjects (n=167) who were selected from subjects registered at the diabetes
      center of Dong-A University Medical Center. We used the ATP III criteria and the
      IDF criteria for the diagnosis of MetS and sorted the subjects into 2 MetS
      groups: one group diagnosed per ATP III criteria (MetSa) and one diagnosed per
      IDF criteria (MetSi). We then compared the clinical characteristics, metabolic
      parameters (homeostasis model assessment of insulin resistance, aspartate
      aminotransferase, alanine aminotransferase, and uric acid values) and co
      morbidities (prevalence of microalbuminuria, fatty liver, and cardiovascular
      disease) between the MetSa, MetSi, and discordant MetS groups. RESULTS: The
      prevalence of MetS in the MetSa group (73.6%) was higher than in the MetSi group
      (62.2%). The MetS prevalence in the discordant group was 11.4%. The discordant
      group showed no significant differences in clinical characteristics (except waist
      circumference and body mass index), metabolic parameters, or prevalence of co
      morbidities, as compared with subjects with MetS by both criteria. CONCLUSION: In
      this study, cardio-metabolic features of the subjects diagnosed with MetS using
      ATP III criteria, but not IDF criteria, are not significantly different from
      those of subjects diagnosed with MetS using both criteria.

PMID- 23130321
TI  - Effects of a 6-Month Exenatide Therapy on HbA1c and Weight in Korean Patients
      with Type 2 Diabetes: A Retrospective Cohort Study.
AB  - BACKGROUND: While many studies have shown the good efficacy and safety of
      exenatide in patients with diabetes, limited information is available about
      exenatide in clinical practice in Korean populations. Therefore, this
      retrospective cohort study was designed to analyze the effects of exenatide on
      blood glucose level and body weight in Korean patients with type 2 diabetes
      mellitus. METHODS: We reviewed the records of the patients with diabetes who
      visited Seoul St. Mary's Hospital and for whom exenatide was prescribed from June
      2009 to October 2011. After excluding subjects based on their race/ethnicity,
      medical history, whether or not they changed more than 2 kinds of oral
      hypoglycemic agents with exenatide treatment, loss to follow-up, or whether they
      stopped exenatide therapy within 6 months, a total of 52 subjects were included
      in the final analysis. RESULTS: The mean glycated hemoglobin (HbA1c) level and
      weight remarkably decreased from 8.5+/-1.7% to 6.7+/-1.0% (P<0.001) and from
      82.3+/-15.8 kg to 78.6+/-16.3 kg (P<0.001), respectively. The multiple regression
      analysis indicated that the reduction in HbA1c level was significantly associated
      with a shorter duration of diabetes, a higher baseline HbA1c level, and greater
      weight reduction, whereas weight loss had no significant correlation with other
      factors. No severe adverse events were observed. CONCLUSION: These results
      suggest that a 6-month exenatide injection therapy significantly improved
      patients' HbA1c levels and body weights without causing serious adverse effects
      in Korean patients with type 2 diabetes.

PMID- 23130322
TI  - The risk of bladder cancer in korean diabetic subjects treated with pioglitazone.
AB  - BACKGROUND: There is growing concern regarding the increased incidence of bladder
      cancer in diabetic patients using pioglitazone. This study aimed to investigate
      the association between bladder cancer and the use of pioglitazone in Korean
      diabetics. METHODS: This retrospective, matched case-control study included a
      case group (n=329) of diabetic patients with bladder cancer who presented at the
      Severance Hospital from November 2005 to June 2011. The control group consisted
      of patients without bladder cancer (1:2 ratio matching for sex and age, n=658)
      who were listed on the Severance Hospital diabetes registry. RESULTS: The
      percentage of subjects who had ever used pioglitazone was significantly lower in
      the case group than in the control group (6.4% vs. 15.0%, P<0.001). Multivariate
      conditional logistic analysis revealed that independent factors affecting bladder
      cancer were smoking (odds ratio [OR], 11.64; 95% confidence interval [CI], 6.56
      to 20.66; P<0.001), coexisting cancer (OR, 6.11; 95% CI, 2.25 to 16.63; P<0.001),
      and hemoglobin levels (OR, 0.78; 95% CI, 0.69 to 0.88; P<0.001). The OR of the
      history of pioglitazone use was 2.09 and was not significantly different between
      the two groups (95% CI, 0.26 to 16.81; P=0.488). CONCLUSION: A relationship
      between pioglitazone use and incidence of bladder cancer was not observed in
      Korean diabetic patients. This suggests that the risk for bladder cancer in
      Korean diabetic subjects treated with pioglitazone might be different from that
      of Caucasian populations. Large-scale, well-designed and multi-center studies are
      needed to further evaluate this relationship.

PMID- 23130323
TI  - Correlations between Glucagon Stimulated C-peptide Levels and Microvascular
      Complications in Type 2 Diabetes Patients.
AB  - BACKGROUND: This study aimed to investigate whether stimulated C-peptide is
      associated with microvascular complications in type 2 diabetes mellitus (DM).
      METHODS: A cross-sectional study was conducted in 192 type 2 diabetic patients.
      Plasma basal C-peptide and stimulated C-peptide were measured before and 6
      minutes after intravenous injection of 1 mg glucagon. The relationship between C
      peptide and microvascular complications was statistically analyzed. RESULTS: In
      patients with retinopathy, basal C-peptide was 1.9+/-1.2 ng/mL, and stimulated C
      peptide was 2.7+/-1.6 ng/mL; values were significantly lower compared with
      patients without retinopathy (P=0.031 and P=0.002, respectively). In patients
      with nephropathy, basal C-peptide was 1.6+/-0.9 ng/mL, and stimulated C-peptide
      was 2.8+/-1.6 ng/mL; values were significantly lower than those recorded in
      patients without nephropathy (P=0.020 and P=0.026, respectively). Stimulated C
      peptide level was associated with increased prevalence of microvascular
      complications. Age-, DM duration-, and hemoglobin A1c-adjusted odds ratios for
      retinopathy in stimulated C-peptide value were 4.18 (95% confidence interval
      [CI], 1.40 to 12.51) and 3.35 (95% CI, 1.09 to 10.25), respectively. The multiple
      regression analysis between nephropathy and C-peptide showed that stimulated C
      peptide was statistically correlated with nephropathy (P=0.03). CONCLUSION: In
      patients with type 2 diabetes, the glucagon stimulation test was a relatively
      simple method of short duration for stimulating C-peptide response. Stimulated C
      peptide values were associated with microvascular complications to a greater
      extent than basal C-peptides.

PMID- 23130324
TI  - Letter: Balsamic Vinegar Improves High Fat-Induced Beta Cell Dysfunction via Beta
      Cell ABCA1 (Diabetes Metab J 2012;36:275-9).

PMID- 23130325
TI  - Response: Balsamic Vinegar Improves High Fat-Induced Beta Cell Dysfunction via
      Beta Cell ABCA1 (Diabetes Metab J 2012;36:275-9).

PMID- 23130326
TI  - Implementation of guidelines, allergy programs, and the October issue.

PMID- 23130327
TI  - Management of allergic rhinitis in general practitioners.
AB  - For patients suffering from allergic rhinitis (AR), general practitioners (GPs)
      are often their first source of medical advice. It is one of the top-ten reasons
      for a visit to the primary care clinics and AR was estimated to be 10-40% of the
      total patient visits in about 50% of the primary care clinics. The standard of
      management for AR among GPs is thus a key outcome assessment of AR management and
      implementation of international guidelines in general healthcare practice.

PMID- 23130328
TI  - Eosinophilic esophagitis: which role for food and inhalant allergens?
AB  - Eosinophilic esophagitis is a chronic inflammatory disease of the esophagus,
      immune/antigens mediated, whose incidence is increasing both in adults and
      pediatric population. It is clinically characterised by symptoms related to
      esophageal dysfunction and associated with eosinophil-predominant esophageal
      inflammation. The role of atopy has been clearly demonstrated both in
      epidemiological and experimental studies and has important implications for
      diagnosis and therapy. In fact, many evidences show that food and inhalant
      allergens represent the most important factors involved in the progress of the
      disease. Several studies have reported that, in a range between 50 and 80%,
      patients with eosinophilic esophagitis have a prior history of atopy, and for
      them, the presence of allergic rhinitis, asthma or atopic dermatitis is frequent.
      Skin tests are able to identify in most patients the allergens involved, allowing
      a correct dietary approach in order to achieve the remission of symptoms and the
      biopsy normalization.

PMID- 23130329
TI  - Immediate hypersensitivity reactions to IV non-ionic iodinated contrast in
      computed tomography.
AB  - BACKGROUND: With use of computed tomography (CT), intravenous contrast media is
      used routinely to help define anatomy and identify any pathology. Non-ionic
      iodinated contrast agents have largely replaced ionic agents and although rare,
      reactions to contrast are still important and more so with the continual increase
      in CT examinations in the last decade. OBJECTIVE: To examine the incidence,
      severity and risk factors of immediate hypersensitivity reactions to intravenous
      non-ionic iodinated contrast in CT. METHODS: Data of consecutive patients in an
      Australian tertiary hospital who developed immediate hypersensitivity reactions
      to intravenous iopromide during CT were collected and compared with the results
      of all contrast CTs performed over a four year period. Chi-square statistics and
      odds ratio are calculated on the variables of age, gender, referral source and
      seasons of the study. RESULTS: Forty-seven patients had immediate
      hypersensitivity reactions of 29,962 patients who underwent contrast CT (0.16%).
      Thirty-three patients (70%) had a mild reaction, 11 (23%) moderate and three (7%)
      severe. Sixteen (34%) were male and 31 (66%) were female. Sixty-eight percent
      were under 55-years of age. Reactions occurred in 0.35% (34 patients) of all
      outpatients, 0.07% (6 patients) of all emergency patients, and 0.06% (7 patients)
      of all in-patients. Eighteen (38%) occurred in spring, seven (15%) in summer, 17
      (36%) in autumn and five (11%) in winter. There is a statistically significant
      higher risk of contrast reactions in females (Odds Ratio [OR] 2.41 p = 0.005),
      patients younger than 55-years old (OR 2.46, p = 0.005), outpatients (OR 5.42, p
      < 0.001) and CTs performed in spring and autumn (OR 2.77, p = 0.002). CONCLUSION:
      The incidence of immediate hypersensitivity reactions in contrast CT is low and
      mostly mild. Risk factors include female, younger than 55-years of age,
      outpatients and CT examinations performed in spring and autumn. This is the first
      study to observe such a seasonal variation.

PMID- 23130330
TI  - Differences in airway inflammation according to atopic status in patients with
      chronic rhinitis.
AB  - BACKGROUND: Chronic rhinitis is a heterogeneous group of diseases that cause
      nasal inflammation. And the nose may be a window into the lung in the concept of
      "one airway one disease." OBJECTIVE: This study was conducted to evaluate
      differences between the different forms of chronic rhinitis in terms of lower
      airway inflammation. METHODS: Patients that attended the allergy clinic and
      presented with moderate/severe persistent rhinitis symptoms for more than 1 year
      were enrolled. The patients with chronic rhinitis were classified into two groups
      (house dust mites [HDM]-sensitive allergic rhinitis [AR] or non-allergic rhinitis
      [NAR]) according to the presence of atopy, and additionally according to nasal
      polyposis and airway hyperresponsiveness, respectively. Medical records were
      reviewed and the mRNA expression levels of IL-5, IFN-gamma, TGF-beta1, IL-17A,
      and IL-25 were evaluated in induced sputum samples in each group. RESULTS:
      Induced sputum samples of 53 patients were evaluated. Patients with NAR were
      significantly older than patients with HDM-sensitive AR (p < 0.05). Nasal
      polyposis was more prevalent in NAR patients than in HDM-sensitive AR patients
      (10.2% vs. 62.5%, p < 0.001). The expression levels of IL-17A mRNA were higher in
      NAR patients, regardless of the presence of airway hyperresponsiveness (p =
      0.005). CONCLUSION: These results suggest that patients with different forms of
      chronic rhinitis could have different inflammatory environments in their lower
      airway and NAR patients might have bronchial inflammation related to the elevated
      levels of IL-17A compared to HDM-sensitive AR patients.

PMID- 23130331
TI  - Interferon-alpha inhibits airway eosinophilia and hyperresponsiveness in an
      animal asthma model [corrected].
AB  - BACKGROUND: Asthma is characterized by a chronic inflammatory process involving
      high numbers of inflammatory cells and mediators which have multiple inflammatory
      effects on the airway. Interferon (IFN)-alpha, which is used widely for treating
      chronic hepatitis C, is reported to have an effect on patients with Churg-Strauss
      syndrome. Therefore, it may also be suitable for patients with severe asthma.
      OBJECTIVE: We studied the effect of IFN-alpha on airway eosinophilia in a guinea
      pig model of asthma and the expression of adhesion molecules on human eosinophils
      and vascular endothelial cells. METHODS: After antigen challenge, airway
      hyperresponsiveness and airway eosinophilia were measured in a guinea pig asthma
      model with or without airway IFN-alpha administration. Expression of adhesion
      molecules on eosinophils and cultured human umbilical vein endothelial cells
      (HUVECs) was also evaluated with or without IFN-alpha. RESULTS: IFN-alpha
      inhibited eosinophil recruitment into the tracheal wall and improved airway
      hyperresponsiveness in sensitized guinea pigs. IFN-alpha also significantly
      suppressed IL-1 beta-induced intercellular adhesion molecule-1 (ICAM-1)
      expression on HUVECs. However, IFN-alpha did not suppress platelet-activating
      factor-induced macrophage antigen-1 expression on human eosinophils. IFN-alpha
      significantly inhibited eosinophil adhesion to IL-1 beta-induced HUVECs and
      migration through IL-1 beta induced HUVECs. CONCLUSION: The findings suggest that
      the modulation of ICAM-1 in lung with pre-existing inflammation following
      treatment with IFN-alpha may be a novel and selective treatment for control of
      chronic airway inflammation and hyperresponsiveness associated with asthma.

PMID- 23130332
TI  - Contribution of serum IL-4 and IgE to the early prediction of horse serum
      allergies in guinea pigs.
AB  - BACKGROUND: Horse serum (HS) was a strong allergen for xenogeneic animals.
      However, the methods of test for allergen didn't authorized in Pharmacopeia of
      the United States, European Pharmacopeia, Japanese Pharmacopeia and British
      Pharmacopeia. Thus, new methods of test for allergen are required to control drug
      allergy. OBJECTIVE: To propose a new method for detecting horse serum induced
      allergic reactions of guinea pigs earlier. METHODS: Guinea pigs were sensitized
      successively by injecting different concentration of HS intravenously once a day
      for three times, serum level of IL-4 and total IgE were detected by method of
      enzyme linked immunosorbent assay (ELISA) before guinea pigs were challenged by
      injecting HS intravenously only once, and the results were compared with routine
      method of sensitization by injecting HS intraperitoneally every other day for
      three times. RESULTS: Serum level of IL-4 and total IgE increased significantly
      before guinea pigs were challenged, either in day 8 after intravenous
      sensitization (10%HS, 0.5 mL) or in day 14 and day 21 after intraperitoneal
      sensitization (10%HS, 0.5 mL), and allergic reactions occurred in all guinea pigs
      after challenged by injecting HS (10%, 1.0 mL) only once. CONCLUSION: It provides
      a new way to predict whether HS or other drugs can provoke allergic reactions
      earlier by detecting the serum level of IL-4 and total IgE in d8 after
      intravenous sensitization, this has a good application value in drug emergency
      test.

PMID- 23130333
TI  - Effect of bathing on atopic dermatitis during the summer season.
AB  - BACKGROUND: There are little objective data regarding the optimal practice
      methods of bathing, although bathing and the use of moisturizers are the most
      important facets to atopic dermatitis (AD) management. OBJECTIVE: We performed
      this study to evaluate the effect of bathing on AD. METHODS: Ninety-six children
      with AD were enrolled during the summer season. Parents were educated to bathe
      them once daily with mildly acidic cleansers, and to apply emollients for 14
      days. Parents recorded the frequency of bathing and skin symptoms in a diary.
      Scoring AD (SCORAD) scores were measured at the initial and follow-up visits.
      Patients were divided into two groups, based on the compliance of bathing; poor
      compliance was defined as >= 2 bathless days. RESULTS: There was an improvement
      of SCORAD score, itching, and insomnia in the good compliance group (all p <
      0.001). The mean change in SCORAD score from the baseline at the follow-up visit
      was greater in the good compliance group than the poor compliance group (p =
      0.038). CONCLUSION: Daily bathing using weakly acidic syndets can reduce skin
      symptoms of pediatric AD during the summer season.

PMID- 23130334
TI  - The Finnish Allergy Programme 2008-2018 - scientific rationale and practical
      implementation.
AB  - There are no nationwide, comprehensive public health programmes on allergic
      disorders with set goals and systematic follow-up. The Finnish initiative is
      based on the idea that the so called allergy epidemic in modern, urban societies
      is caused by inadequately developed or broken tolerance. The immune system is not
      trained to make the difference between danger and non-danger (allergy) or the
      difference between self and non-self (autoimmune diseases). The immune
      dysfunction leads to inappropriate inflammatory responses and clinical symptoms.
      The 10-year implementation programme is aimed to reduce burden of allergies both
      at the individual and societal levels. This is done by increasing both
      immunological and psychological tolerance and changing attitudes to support
      health instead of medicalising common and mild allergy symptoms. Severe forms of
      allergy are in special focus, e.g. asthma attacks are prevented proactively by
      improving disease control with the help of guided self-management. Networking of
      allergy experts with primary care doctors and nurses as well with pharmacists is
      the key for effective implementation. Non-governmental organizations have started
      a campaign to increase allergy awareness and knowledge among patients and general
      public. It is time to act, when allergic individuals are becoming a majority of
      Western populations and their numbers are in rapid increase worldwide. The first
      results of the Finnish Programme indicate that allergy burden can be reduced with
      relatively simple means.

PMID- 23130335
TI  - Biphasic anaphylaxis to gemifloxacin.
AB  - Anaphylaxis have been documented as adverse effects of ciprofloxacin, ofloxacin,
      norfloxacin, levofloxacin, and moxifloxacin. However resistant and biphasic
      anaphlylactic reactions to gemifloxacin have not been reported to date.
      Management of severe anaphylaxis in the elderly can be complicated by concurrent
      medications such as beta (beta) adrenergic, alpha (alpha) adrenergic blockers and
      angiotensin-converting enzyme (ACE) inhibitors. We report here in the case of a
      60-year-old male who was taking on ACE inhibitor, alpha and beta blockers and
      experienced a severe, resistant and biphasic anaphlylactic reaction to
      gemifloxacin mesylate.

PMID- 23130336
TI  - Correlations between Janus kinase 2 V617F allele burdens and clinicohematologic
      parameters in myeloproliferative neoplasms.
AB  - BACKGROUND: This study evaluated potential correlations between the allele burden
      of the Janus kinase 2 (JAK2) V617F mutation and clinicohematologic
      characteristics in patients with myeloproliferative neoplasms (MPN). METHODS:
      Clinical and hematologic features were reviewed for 103 MPN patients, including
      patients with polycythemia vera (PV, 22 patients), essential thrombocythemia (ET,
      64 patients), and primary myelofibrosis (PMF, 17 patients). JAK2 V617F allele
      status and allele burdens were measured by allele-specific PCR and
      pyrosequencing, respectively. RESULTS: The JAK2 V617F mutation was detected in
      95.5%, 68.8%, and 52.9% of PV, ET, and PMF patients, respectively. JAK2 V617F
      positive ET patients were significantly older and exhibited higher neutrophil
      fractions, a higher frequency of thrombotic events, and a higher myelofibrosis
      rate than JAK2 V617F-negative patients (P <0.05). PV patients carried the highest
      mean T allele burden (66.0%+/-24.9%) compared with ET (40.5%+/-25.2%) and PMF
      patients (31.5%+/-37.0%) (P =0.00). No significant correlations were detected
      between V617F allele burden and patient age, white blood cell count, Hb, Hct, or
      the platelet count for PV, ET, or PMF patients. ET patients with organomegaly had
      a higher JAK2 V617F allele burden (53.4%+/-23.7%) than patients without
      organomegaly (35.6%+/-24.3%) (P =0.03). CONCLUSIONS: The JAK2 V617F mutational
      status and its allele burden correlate with the clinicohematologic phenotypes of
      ET patients, including older age, higher neutrophil count, and greater rates of
      organomegaly, thrombotic events, and myelofibrosis. For PV and PMF patients,
      larger-scale studies involving more MPN patients are needed.

PMID- 23130337
TI  - Correction of pseudoreticulocytosis in leukocytosis samples using the Sysmex XE
      2100 analyzer depends on the type and number of white blood cells.
AB  - BACKGROUND: The reticulocyte count is a good marker of erythropoietic activity of
      the bone marrow. In the mid-1990s, automated flow cytometric analysis replaced
      microscopy for the quantification of reticulocytes. Leukocytosis cases with an
      erroneously high reticulocyte count and a high immature reticulocyte fraction
      (IRF) have been reported. In this study, we analyzed reticulocyte counts in
      leukocytosis samples, in an effort to identify a correction method. METHODS: The
      study comprised of 21 samples from 16 leukocytosis patients. Results of
      reticulocyte analyses obtained using a XE-2100 hematology analyzer (Sysmex,
      Japan) were compared with those obtained using the supravital staining technique,
      which is a reference method. If the samples showed erroneously high reticulocyte
      counts and IRF, they were reanalyzed after serial dilution with isotonic
      solution. RESULTS: Five samples from 4 patients showed erroneously elevated
      reticulocyte counts and/or IRF on the XE-2100 analyzer. They displayed abnormal
      reticulocyte scattergrams, with 4 of 5 cases indicated by a flag. The white blood
      cell (WBC) fractions overlapped with the reticulocyte regions, especially with
      the IRF. Diagnoses and blast counts were variable when such errors occurred; WBC
      counts varied from 218.19*10(9)/L to 725.14*10(9)/L. The errors were corrected by
      simple dilution with isotonic solution. However, the corrective WBC counts
      differed according to individual cases. CONCLUSIONS: When leukocytosis samples
      exhibit an abnormal reticulocyte scattergram with a flag, or an abnormally high
      IRF, we recommend the dilution of the sample with isotonic solution to a WBC
      count of about 100.00*10(9)/L, followed by reanalysis of the reticulocyte count
      and reticulocyte scattergram.

PMID- 23130338
TI  - Evaluation of a multiplex real-time PCR assay for the detection of respiratory
      viruses in clinical specimens.
AB  - BACKGROUND: In this study, we evaluated the analytical performance and clinical
      potential of a one-step multiplex real-time PCR assay for the simultaneous
      detection of 14 types of respiratory viruses using the AdvanSure RV real-time PCR
      Kit (LG Life Sciences, Korea). METHODS: Three hundred and twenty clinical
      specimens were tested with the AdvanSure RV real-time PCR Kit and conventional
      multiplex reverse transcription (RT)-PCR assay. The assay results were analyzed
      and the one-step AdvanSure RV real-time PCR Kit was compared with the
      conventional multiplex RT-PCR assay with respect to the sensitivity and
      specificity of the detection of respiratory viruses. RESULTS: The limit of
      detection (LOD) was 1.31 plaque-forming units (PFU)/mL for human rhinoviruses
      (hRVs), 4.93 PFU/mL for human coronavirus HCoV-229E/NL63, 2.67 PFU/mL for human
      coronavirus HCoV-OC43, 18.20 PFU/mL for parainfluenza virus 1 (PIV)-1, 24.57
      PFU/mL for PIV-2, 1.73 PFU/mL for PIV-3, 1.79 PFU/mL for influenza virus group
      (Flu) A, 59.51 PFU/mL for FluB, 5.46 PFU/mL for human respiratory syncytial virus
      (hRSV)-A, 17.23 PFU/mL for hRSV-B, 9.99 PFU/mL for human adenovirus (ADVs). The
      cross-reactivity test for this assay against 23 types of non-respiratory viruses
      showed negative results for all viruses tested. The agreement between the one
      step AdvanSure multiplex real-time PCR assay and the conventional multiplex RT
      PCR assay was 98%. CONCLUSIONS: The one-step AdvanSure RV multiplex real-time PCR
      assay is a simple assay with high potential for specific, rapid and sensitive
      laboratory diagnosis of respiratory viruses compared to conventional multiplex RT
      PCR.

PMID- 23130339
TI  - Methicillin-resistant Staphylococcus aureus in nasal surveillance swabs at an
      intensive care unit: an evaluation of the LightCycler MRSA advanced test.
AB  - BACKGROUND: We compared the LightCycler MRSA advanced test (Roche Diagnostics,
      Germany) with enrichment culture methods to evaluate the relative diagnostic
      performance of the LightCycler MRSA advanced test for active surveillance in a
      high-prevalence setting. METHODS: A total of 342 nasal swab specimens were
      obtained from patients in the intensive care unit at admission and on the seventh
      day for follow-up. The results of LightCycler MRSA advanced test were compared to
      those of the enrichment culture. For discrepant results, mecA gene PCR was
      performed. RESULTS: For the detection of methicillin-resistant Staphylococcus
      aureus (MRSA), the LightCycler MRSA advanced test showed 98.5% sensitivity and
      78.6% specificity and had positive and negative predictive values of 75.0% and
      98.8%, respectively. A total of 46 samples had discrepant results between the
      LightCycler MRSA advanced test and enrichment culture. Of the 44 specimens that
      were positive in the LightCycler MRSA advanced test but negative by enrichment
      culture, mecA genes were detected in 37 specimens. In addition, of the original
      44 cases, 21 patients had a history of MRSA colonization or infection within the
      last month; of those 21 specimens, 20 were positive for mecA gene as shown by
      PCR. Seven mecA-negative discrepant specimens comprised 3 methicillin-sensitive
      S. aureus-culture positive and only 2 patients had MRSA infections. CONCLUSIONS:
      Despite its low specificity and positive predictive value, the LightCycler MRSA
      advanced test could serve as a rapid test for patients colonized with MRSA.

PMID- 23130340
TI  - Clonal spread of carbapenem non-susceptible Acinetobacter baumannii in an
      intensive care unit in a teaching hospital in China.
AB  - BACKGROUND: This study was aimed to investigate the genetic diversity and
      antibiotic resistance profile of the nosocomial infection agent Acinetobacter
      baumannii from a medical intensive care unit (ICU) in a teaching hospital in
      Suzhou, China. METHODS: The genetic relationship among A. baumannii isolates in
      an ICU was investigated using multilocus sequence typing (MLST). The antibiotic
      resistance pattern was determined by performing an antibiotic susceptible test,
      which included an agar dilution method and an E-test method. Resistant
      determinants, e.g., carbapenemase genes, metallo-beta-lactamases, and class 1
      integron, were analyzed by specific PCR and DNA sequencing. RESULTS: In the
      present study, 33 non-duplicate isolates were identified as 5 existing sequence
      types (STs) (ST92, ST75, ST112, ST145, and ST345) and 1 new sequence type STn,
      which has a G-A mutation at nt268 on ropD40 of ST251. These results reveal
      limited diversity in carbapenem non-susceptible A. baumannii (CNSAb) isolates in
      our ICU, which are comprised of only 2 distinct STs, with ST92 and ST75
      clustering into a clonal complex (CC) 92. Most CNSAb isolates (94.4%, 17/18)
      harbored the OXA-23 gene, while no carbapenem-susceptible A. baumannii (CSAb)
      isolates harbored it. In addition, 66.7% (22/33) isolates were positive for class
      1 integrase, and gene cassette analysis showed there are 3 gene arrays among
      them, i.e., aacA4-catB8-aadA1 (77.3%, 17/22), aacA4 (22.7%, 5/22), and aacC1-orfX
      orfX'-aadA1 (4.5%, 1/22). CONCLUSIONS: When all these data are combined, the
      antibiotic resistance and wide distribution of CNSAb isolates in our ICU are
      probably caused by expansion of the CC92 clone.

PMID- 23130341
TI  - Elecsys hepatitis B surface antigen quantitative assay: performance evaluation
      and correlation with hepatitis B virus DNA during 96 weeks of follow-up in
      chronic hepatitis B patients.
AB  - BACKGROUND: Treatment for chronic hepatitis B aims to suppress virus replication
      and virus sequestration in hepatocytes. Covalently closed circular (ccc) DNA is
      the template for transcription of viral genes and is responsible for viral
      persistence. However, limited data are available for quantification of hepatitis
      B surface antigen (HBsAg) in Korea. METHODS: We evaluated the Elecsys HBsAg II
      quant assay (Roche Diagnostics, USA) for within-run, between-run, and between-day
      precisions, linearity, carryover, and clinical specificity. In total, 156 serum
      samples were evaluated for correlation between HBsAg and hepatitis B virus (HBV)
      DNA. Serial samples were obtained from 10 patients at 0, 12, 24, 48, 72, and 96
      weeks during follow-up. RESULTS: The assay detected HBsAg in a linear range of
      0.5-48,696 IU/mL. Within-run, between-run, and between-day CVs were 2.9-4.1%, 0
      1.5%, and 1.5-4.9%, respectively. Cross-reactivity between potentially
      interfering substances was absent, and the carryover rate was 0.00002%. The
      correlation of measurements between the Elecsys assay and HBV DNA PCR was weak
      (r=0.438, P=0.002). For predicting virologic response, cutoff values of 10,275
      IU/mL and 3,846 IU/mL at 12 and 24 weeks after treatment initiation showed
      positive predictive values of 77.1% and 85% and negative predictive values of
      84.6% and 50%, respectively. CONCLUSIONS: The Elecsys HBsAg II quant assay showed
      good performance for precision, linearity, carryover rate, and specificity. HBsAg
      level at baseline, 12 weeks, and 24 weeks after treatment initiation can predict
      virologic response, and the assay can be used for HBsAg quantification in
      clinical practice.

PMID- 23130342
TI  - Antifungal susceptibility to amphotericin B, fluconazole, voriconazole, and
      flucytosine in Candida bloodstream isolates from 15 tertiary hospitals in Korea.
AB  - The in vitro antifungal susceptibility of 636 Candida bloodstream isolates
      collected from 15 tertiary hospitals in Korea was determined using the Vitek-2
      yeast susceptibility system (bioMerieux, France). Overall susceptibility rates
      were 98.1%, 95.9%, 99.1%, and 97.3% for amphotericin B, fluconazole,
      voriconazole, and flucytosine, respectively. The results show that the rates of
      resistance to 4 antifungal drugs remain low among Candida bloodstream isolates in
      Korea.

PMID- 23130343
TI  - Sensitization to multiple rh antigens by transfusion of random donor platelet
      concentrates in a -D- phenotype patient.
AB  - The -D- phenotype is a rare Rh phenotype that strongly expresses D antigen
      without C, c, E, or e antigens. In -D- phenotype individuals, anti-Rh17 (Hr(o))
      is commonly found if there is a history of pregnancy or transfusion with red
      blood cells (RBCs) that express C, c, E, or e antigens. We report the first case
      of a -D- phenotype patient with multiple Rh antibodies including anti-Rh17 who
      had a history of two occasions of transfusion with eight random donor platelet
      concentrates two and six years ago. We found that a trivial amount of RBCs in the
      platelet components was able to trigger sensitization to RBC antigens, especially
      the highly immunogenic and clinically significant Rh antigens, including C, c, E,
      e or CcEe polypeptides. To avoid unnecessary sensitization and to minimize the
      risk of hemolytic transfusion reactions in patients with this rare Rh phenotype,
      a modified strategy for pretransfusion screenings needs to be discussed in the
      field of transfusion medicine.

PMID- 23130344
TI  - A case of Helicobacter cinaedi bacteremia in an asplenic patient.
AB  - Helicobacter cinaedi is an enterohepatic species. It can cause bacteremia,
      gastroenteritis, and cellulitis, particularly in immunocompromised individuals,
      such as those with acquired immunodeficiency syndrome, malignancy, or alcoholism.
      There are no previous reports of H. cinaedi infection in Korea. A 71-yr-old man
      was admitted to the emergency room because of dyspnea on November 9, 2011. He had
      undergone splenectomy 3 yr ago because of immune hemolytic anemia. Chest plain
      radiography revealed bilateral pleural effusion. He developed fever on hospital
      day (HD) 21. Three sets of blood cultures were taken, and gram-negative spiral
      bacilli were detected in all aerobic vials. The isolate grew in tiny colonies on
      chocolate agar after 3-day incubation under microaerophilic conditions. This
      organism tested positive for catalase and oxidase, and negative for urease. The
      16S rRNA gene sequence of this isolate exhibited 99.8% homology with the
      published sequence of H. cinaedi CCUG 18818(T) (GenBank accession no.
      ABQT01000054) and 98.5% homology with the sequence of Helicobacter bilis Hb1(T)
      (GenBank accession no. U18766). The patient was empirically treated with
      piperacillin/tazobactam and levofloxacin, and discharged with improvement on HD
      31. To our knowledge, this is the first report of H. cinaedi bacteremia in an
      asplenic patient. Asplenia appears to be a risk factor for H. cinaedi bacteremia.

PMID- 23130345
TI  - Subcutaneous phaeohyphomycosis caused by Exophiala salmonis.
AB  - We report a case of subcutaneous infection in a 55-yr-old Korean diabetic patient
      who presented with a cystic mass of the ankle. Black fungal colonies were
      observed after culturing on blood and Sabouraud dextrose agar. On microscopic
      observation, septated ellipsoidal or cylindrical conidia accumulating on an
      annellide were visualized after staining with lactophenol cotton blue. The
      organism was identified as Exophiala salmonis by sequencing of the ribosomal DNA
      internal transcribed spacer region. Phaeohyphomycosis is a heterogeneous group of
      mycotic infections caused by dematiaceous fungi and is commonly associated with
      immunocompromised patients. The most common clinical manifestations of
      subcutaneous lesions are abscesses or cystic masses. To the best of our
      knowledge, this is the first reported case in Korea of subcutaneous
      phaeohyphomycosis caused by E. salmonis that was confirmed by molecular analysis
      and identification of morphological characteristics. This case suggests that E.
      salmonis infections are no longer restricted to fish.

PMID- 23130346
TI  - The first Korean case report of anti-Gerbich.
AB  - In this study, we report the first Korean case of an anti-Gerbich (Ge)
      alloantibody to a high-incidence antigen that belongs to the Ge blood group
      system. The alloantibody was detected in a middle-aged Korean woman who did not
      have a history of transfusion. Her blood type was B+, and findings from the
      antibody screening test revealed 1+ reactivity in all panels except the
      autocontrol. The cross-matching test showed incompatible results with all 5
      packed red blood cells. Additional blood type antigen and antibody tests
      confirmed the anti-Ge alloantibody. While rare, cases of hemolytic transfusion
      reaction or hemolytic disease in newborns due to anti-Ge have been recently
      reported in the literature. Therefore, additional further studies on
      alloantibodies to high-incidence antigens, including anti-Ge, are necessary in
      the future.

PMID- 23130347
TI  - Additional genomic aberrations identified by single nucleotide polymorphism array
      based karyotyping in an acute myeloid leukemia case with isolated del(20q)
      abnormality.
AB  - Prognosis is known to be better in cases with isolated chromosomal abnormalities
      than in those with complex karyotypes. Accordingly, del(20q) as an isolated
      abnormality must be distinguished from cases in which it is associated with other
      chromosomal rearrangements for a better stratification of prognosis. We report a
      case of an isolated del(20q) abnormality with additional genomic aberrations
      identified using whole-genome single nucleotide polymorphism array (SNP-A)-based
      karyotyping. A 39-yr-old man was diagnosed with AML without maturation. Metaphase
      cytogenetic analysis (MC) revealed del(20)(q11.2) as the isolated abnormality in
      100% of metaphase cells analyzed, and FISH analysis using D20S108 confirmed the
      20q deletion in 99% of interphase cells. Using FISH, other rearrangements such as
      BCR/ABL1, RUNX1/RUNX1T1, PML/RARA, CBFB/MYH11, and MLL were found to be negative.
      SNP-A identified an additional copy neutral loss of heterozygosity (CN-LOH) in
      the 11q13.1-q25 region. Furthermore, SNP-A allowed for a more precise definition
      of the breakpoints of the 20q deletion (20q11.22-q13.31). Unexpectedly, the
      terminal regions showed gain on chromosome 20q. The patient did not achieve
      complete remission; 8 months later, he died from complications of leukemic cell
      infiltrations into the central nervous system. This study suggests that a
      presumably isolated chromosomal abnormality by MC may have additional genomic
      aberrations, including CN-LOH, which could be associated with a poor prognosis.
      SNP-A-based karyotyping may be helpful for distinguishing true isolated cases
      from cases in combination with additional genomic aberrations not detected by MC.

PMID- 23130348
TI  - Hemoglobin Andrew-Minneapolis: hemolytic erythrocytosis and severe iron overload
      in toxic liver cirrhosis.

PMID- 23130349
TI  - Rare frameshift mutation Cys475Tyrfs(*)11 in the BCR/ABL kinase domain
      contributes to imatinib mesylate resistance in 2 Korean patients with chronic
      myelogenous leukemia.

PMID- 23130350
TI  - Prevalence of seasonal influenza viruses and pandemic H1N1 virus in Beijing from
      2008 to 2012.

PMID- 23130352
TI  - Interplays between gut microbiota and gene expression regulation by miRNAs.

PMID- 23130353
TI  - Daily variations in ambulance calls for selected causes in Arkhangelsk, Russia:
      potential role of excessive alcohol consumption on weekends.
AB  - OBJECTIVE: To assess daily variations in ambulance calls for cardiovascular
      diseases (CVDs), mental and behavioral disorders, and external causes in
      Arkhangelsk, Northwest Russia, in 2000-2008. STUDY DESIGN: A population-based
      study. METHODS: Data about all ambulance calls during the years 2000-2008 were
      obtained from the Arkhangelsk ambulance station. Information about patient's
      gender, age, doctor's diagnosis according to International Classification of
      Diseases, 10th revision, and the date of call were recorded. Pearson's Chi
      squared tests were used for comparing proportions of ambulance calls across the
      week for CVDs (I00-99), mental and behavioral disorders (F00-F99), and external
      causes (S00-T98, V01-Y98). The ratio of incidence of ambulance calls on Saturday,
      Sunday, and Monday versus the rest of week was also calculated. RESULTS: There is
      a significant daily variation (p < 0.001) in calls for CVDs in men and women aged
      18-59 and women aged 60 years and older, with increased numbers of calls on
      weekends and Mondays varying between 2 and 3% excess calls. For mental and
      behavioral disorders, a similar pattern was found in the age group of 18-59 year
      olds. Ratios for the number of calls during weekends and Mondays vs. the rest of
      the week were 1.05 (95% CI: 1.02-1.08) among women and 1.02 (95% CI: 1.00-1.05)
      among men. For external causes, a significant variation and an increase in
      ambulance calls during Saturdays, Sundays, and Mondays from 4 to 17% excess calls
      was observed for both age and gender groups. CONCLUSIONS: The observed daily
      variations in ambulance calls with an increased number of calls on weekends and
      Mondays for CVDs, mental and behavioral disorders, and external causes may be
      associated with excessive alcohol consumption on the weekends. Further research
      using data on individual levels of alcohol consumption are warranted.

PMID- 23130354
TI  - Detection of acylglycines in urine by 1H and 13C NMR for the diagnosis of inborn
      metabolic diseases.
AB  - A range of inborn metabolic diseases result in abnormal accumulation of
      acylglycines in body fluids. Therefore, detection of these metabolites is
      important for diagnostic purposes. (1)H and (13)C NMR spectroscopies have
      successfully been applied for both qualitative and quantitative determinations of
      various acylglycines in urine samples from patients suffering from metabolic
      diseases connected with excretion of these compounds. Various acylglycines were
      identified in test urine samples from 15 patients suffering from five different
      metabolic diseases, providing information which could be crucial for their
      diagnoses. The paper reports complete (1)H and (13)C NMR data of 11 acylglycines,
      which is essential for this type of NMR analysis of body fluids. NMR spectroscopy
      has been proven effective in determining the presence as well as the levels of
      acylglycines in urine. The proposed method is rapid, simple and requires minimal
      sample treatment.

PMID- 23130355
TI  - Low recombination activity of R region located at both ends of the HIV-1 genome.
AB  - Although two strand transfer events are indispensable for the synthesis of double
      stranded DNA and establishing HIV-1 infection, the molecular basis of these
      phenomena is still unclear. The first obligatory template switching event occurs
      just at the beginning of the virus replication cycle and involves two copies of
      the 97-nucleotide long R region, located one each at the both ends of the HIV-1
      genome (HIV-1 R). Thus, one can expect that the molecular mechanism of this
      process is similar to the mechanism of homologous recombination which operates in
      RNA viruses. To verify the above-mentioned hypothesis, we attempted to assess the
      recombination activity of HIV-1 R. To this end, we tested in vitro, how
      effectively it induces template switching by HIV-1 RT in comparison with another
      well-characterized sequence supporting frequent homologous crossovers in an
      unrelated virus (R region derived from Brome mosaic virus--BMV R). We also
      examined if the RNA sequences neighboring HIV-1 R influence its recombination
      activity. Finally, we tested if HIV-1 R could cause BMV polymerase complex to
      switch between RNA templates in vivo. Overall, our results have revealed a
      relatively low recombination activity of HIV-1 R as compared to BMV R. This
      observation suggests that different factors modulate the efficiency of the first
      obligatory strand transfer in HIV-1 and the homology-driven recombination in RNA
      viruses.

PMID- 23130351
TI  - Human gut microbiota: repertoire and variations.
AB  - The composition of human gut microbiota and their relationship with the host and,
      consequently, with human health and disease, presents several challenges to
      microbiologists. Originally dominated by culture-dependent methods for exploring
      this ecosystem, the advent of molecular tools has revolutionized our ability to
      investigate these relationships. However, many biases that have led to
      contradictory results have been identified. Microbial culturomics, a recent
      concept based on a use of several culture conditions with identification by MALDI
      TOF followed by the genome sequencing of the new species cultured had allowed a
      complementarity with metagenomics. Culturomics allowed to isolate 31 new
      bacterial species, the largest human virus, the largest bacteria, and the largest
      Archaea from human. Moreover, some members of this ecosystem, such as Eukaryotes,
      giant viruses, Archaea, and Planctomycetes, have been neglected by the majority
      of studies. In addition, numerous factors, such as age, geographic provenance,
      dietary habits, antibiotics, or probiotics, can influence the composition of the
      microbiota. Finally, in addition to the countless biases associated with the
      study techniques, a considerable limitation to the interpretation of studies of
      human gut microbiota is associated with funding sources and transparency
      disclosures. In the future, studies independent of food industry funding and
      using complementary methods from a broad range of both culture-based and
      molecular tools will increase our knowledge of the repertoire of this complex
      ecosystem and host-microbiota mutualism.

PMID- 23130356
TI  - A rapid and simple method for detection of type II restriction endonucleases in
      cells of bacteria with high activity of nonspecific nucleases.
AB  - In this work we describe a novel, rapid and simple microscale procedure for
      identification of restriction endonuclease activity in bacteria lysates, which
      contain high levels of non-specific DNA nucleases.

PMID- 23130357
TI  - Improving America's health requires community-level solutions: Folsom revisited.
AB  - Amidst sweeping changes to health care in the 1960s, the broadly influential
      Folsom Commission report, "Health is a Community Affair," never fully achieved
      its vision of galvanizing the creation of Communities of Solution, which were
      empowered to improve health at the local level. Passage of health care reform,
      and persistent concern over poor health outcomes despite runaway spending,
      contemporizes Folsom's call for nationally supported and evaluated, but community
      driven, solutions to the nation's health care challenges.

PMID- 23130358
TI  - WITHDRAWN: The influence of friends, family, and older peers on smoking among
      elementary school students: low-risk students in high-risk schools.

PMID- 23130359
TI  - Meningitis outbreak reveals gaps in US drug regulation.

PMID- 23130360
TI  - Researchers call for reform of US gun control policies.

PMID- 23130361
TI  - Grants aim to boost African genomic research.

PMID- 23130362
TI  - A new dimension for medical education.

PMID- 23130363
TI  - Caregiving as moral experience.

PMID- 23130364
TI  - What's app? sports medicine physicians should not talk double Dutch.

PMID- 23130366
TI  - Evidence for the early involvement of interleukin 17 in human and experimental
      renal allograft rejection.

PMID- 23130365
TI  - A combined index of structure and function for staging glaucomatous damage.
AB  - OBJECTIVES: To present and evaluate a new combined index of structure and
      function (CSFI) for staging and detecting glaucomatous damage. METHODS:
      Observational study including 333 glaucomatous eyes (295 with perimetric glaucoma
      and 38 with preperimetric glaucoma) and 330 eyes of healthy subjects. All the
      eyes were tested with standard automated perimetry and spectral domain optical
      coherence tomography within 6 months. Estimates of the number of retinal ganglion
      cells (RGCs) were obtained from standardautomated perimetry and spectral domain
      optical coherence tomography and a weighted averaging scheme was used to obtain a
      final estimate of the number of RGCs for each eye. The CSFI was calculated as the
      percent loss of RGCs obtained by subtracting estimated from expected RGC numbers.
      The performance of the CSFI for discriminating glaucoma from normal eyes and the
      different stages of disease was evaluated by receiver operating characteristic
      curves. RESULTS: The mean CSFI, representing the mean estimated percent loss of
      RGCs, was 41% and 17% in the perimetric and preperimetric groups, respectively
      (P.001). They were both significantly higher than the mean CSFI in the healthy
      group (P.001). The CSFI had larger receiver operating characteristic curve areas
      than isolated indexes of structure and function for detecting perimetric and
      preperimetric glaucoma and differentiating among early, moderate, and advanced
      stages of visual field loss. CONCLUSION: An index combining structure and
      function performed better than isolated structural and functional measures for
      detection of perimetric and preperimetric glaucoma as well as for discriminating
      different stages of the disease.

PMID- 23130367
TI  - 2012 Frechette Award.

PMID- 23130368
TI  - Pharmacogenetic differences among insulin secretagogues based on KCNJ11/ABCC8
      haplotypes.

PMID- 23130369
TI  - Replication of the association of gene variant near ATM and response to
      metformin.

PMID- 23130370
TI  - [Liver, pancreas, biliary tract cancer].

PMID- 23130371
TI  - Technology and the art and practice of orthodontics.

PMID- 23130372
TI  - [Proceeding of preoperative treatment to jaundice caused by biliary tract
      cancer].

PMID- 23130373
TI  - Proceedings of the 4th China-France Biotherapy and Regenerative Medicine
      International Symposium 2011, June 18-19, 2011, Wuhan, China.

PMID- 23130374
TI  - A specialism of primary dental care? Prim Dent Care 2004;11(1)5-7.

PMID- 23130375
TI  - [Surgical outcome of biliary tract cancer with postoperative chemotherapy].

PMID- 23130376
TI  - Frechette Awards.

PMID- 23130377
TI  - Supporting the radiologist assistant profession.

PMID- 23130378
TI  - Lighting up the brain and breast without radiation.

PMID- 23130379
TI  - Aisha.

PMID- 23130380
TI  - The process of purchasing a motorized health vehicle.
AB  - The purpose of this article is to discuss the process of acquiring a motorized
      health vehicle (MHV), specifically, an MHV for providing mammography services.
      Kaiser Foundation Health Plan of Colorado wanted to make it more convenient for
      its members to get screened for breast cancer, but senior management wanted to
      improve breast cancer screening Healthcare Effectiveness Data and Information Set
      (HEDIS) scores. The selection and purchase of an MHV is a complex process
      utilizing a business plan, RFI, a RFP, and a selection committee. Hurdles upon
      implementation may include issues with staffing, weather, Medicare/Medicaid
      enrollment, communication, and connectivity.

PMID- 23130382
TI  - ICD-10: updates and new codes.

PMID- 23130381
TI  - Things I wish every administrator would think about.
AB  - Every organization and facility has issues they need to address. No place is
      perfect. It is important to be aware of these issues so you can not only fix them
      but provide appropriate monitoring on an ongoing basis to ensure consistent
      compliance. All of the issues described here are "big" issues to address, but
      don't lose heart. Positive change is usually accomplished in incremental steps so
      take it one step at a time and celebrate your progress!

PMID- 23130383
TI  - Radiology equipment maintenance and contract procurement in the UK.
AB  - Radiology equipment maintenance has a similar financial value to new device
      acquisition over the lifetime of the device. Comprehensive style contracts are
      dominant largely due to their ease of use and the potential to control budgetary
      costs, but costs are high. Creative procurement solutions can offer better value.
      The corrective portion of comprehensive contracts is estimated to be between 50%
      (Mobile C-Arm) to 92% (CT), which equates to $29.4 million; 80% of the total
      contract costs within the research population of this study. Many organizations
      could free up cash by better managing their maintenance costs, potentially
      creating funding opportunities for new equipment.

PMID- 23130384
TI  - Introducing a freestanding emergency department.

PMID- 23130385
TI  - Flight data recorder for interventional radiology.
AB  - To test process improvement strategies, a recording system in a new pediatric
      interventional radiology suite was installed modeled after the flight data
      recorders found in modern aviation. Using the resulting data from these
      recordings, a variety of quality and safety improvement projects were planned
      including improving timeout performance and optimizing radiation use. There were
      several challenges, including balancing the need to protect patients during
      efforts to improve teamwork. However, the flight data recorder drove home the
      notion that interventional radiology is a team sport and that improvements can be
      measured by keeping score.

PMID- 23130386
TI  - Management styles and motivation.
AB  - According to a review of the current literature, common managerial styles are
      transformational, transactional, and laissez-faire. When managers expand their
      leadership skills to improve the staff's morale, they must use a combination of
      transformational leadership behaviors and transactional contingent rewards to
      maximize their effectiveness on employees. A motivation theory such as Herzberg
      and Maslow enhances employees' motivation, morale, and satisfaction. Being able
      to motivate, empower, and influence staff improves satisfaction and retention
      levels among the team. A manager's leadership style influences motivation,
      morale, and retention in staff. Leaders are influenced by their educational
      development and the organizational culture. Organizational culture has an impact
      on a manager's style, which is forwarded to their followers.

PMID- 23130387
TI  - Teaming up.

PMID- 23130388
TI  - Anatomy of an incident disclosure: the importance of dialogue.
AB  - BACKGROUND: Disclosure of health care incidents to patients and family members,
      as an ethical imperative, is becoming increasingly prevalent. The experiences of
      a woman whose husband died forms the basis for a case study of how she and her
      family and friends were able to renegotiate clinicians' understandings of what
      had gone wrong and influence their views of what needed to be done in response.
      METHODS: The case was constructed in late 2010 using the replicated single-case
      approach, which involved repeated checking and correcting details of an interview
      with the patient's wife. Her husband, diagnosed with multiple myeloma in 2006,
      was hospitalized in January 2009 following a hip replacement. While in the
      hospital, he received a vasopressin overdose. He died in February 2009. THE
      DISCLOSURE PROCESS: The basis of the disclosure was the drug error, yet the
      patient's wife informed the caller (the head of the ICU), "You've got a greater
      problem than a drug error... you've got a massive, big communication problem
      here." The disclosure process, which unfolded in a series of phone calls and
      meetings, enabled the patient's wife and her family not only to ask questions but
      to put forward their knowledge, views, and concerns, and it moved from
      "disclosing an incident" (the vasopressin overdose) to addressing repeated
      communication failures and inappropriate behaviors. As a result, the disclosure
      process became a genuine dialogue that informed the clinicians as much as the
      family. CONCLUSIONS: This case study expands our understanding of what is
      possible as part of disclosure communication. Patients and family members can and
      should play a critical role in quality improvement and patient safety, given
      their knowledge and questions about the trajectory of care and their passion for
      ensuring that similar incidents do not recur to harm others.

PMID- 23130389
TI  - Editorial: Advanced data analytics in performance improvement.

PMID- 23130390
TI  - A framework for analyzing data from the electronic health record: verbal orders
      as a case in point.
AB  - BACKGROUND: Investment in health care information technology is resulting in a
      large amount of data electronically captured during patient care. These databases
      offer the opportunity to implement ongoing monitoring and analysis of processes
      with important patient care quality and safety implications to an extent that was
      previously not feasible with paper-based records. Thus, there is a growing need
      for analytic frameworks to efficiently support both ongoing monitoring and as
      needed periodic detailed analyses to explore particular issues. One patient care
      process-the use of verbal orders-is used as a case in point to present a
      framework for analyzing data pulled from electronic health record (EHR) and
      computerized provider order entry systems. METHODS: Longitudinal and cross
      sectional data on verbal orders (VOs) were analyzed at University of Missouri
      Health Care, Columbia, an academic medical center composed of five specialty
      hospitals and other care settings. RESULTS: A variety of verbal order analyses
      were conducted, addressing longitudinal-order patterns, provider-specific
      patterns, order content and urgency, associated computer-generated alerts, and
      compliance with institutional policy of a provider cosignature within 48 hours.
      For example, at the individual prescriber level, in July 2011 there were 14
      physicians with 50 or more VOs, with the top 2 having 253 and 233 individual VOs,
      respectively. CONCLUSIONS: Taking advantage of the automatic data-capture
      features associated with health information technologies now being incorporated
      into clinical work flows offers new opportunities to expand the ability to
      analyze care processes. Health care organizations can now study and statistically
      model, understand, and improve complex patient care processes.

PMID- 23130391
TI  - Improving medication safety with accurate preadmission medication lists and
      postdischarge education.
AB  - BACKGROUND: Gathering a complete preadmission medication list (PAML) at admission
      remains an essential component of medication reconciliation, as is providing the
      patient with a written medication list at the time of hospital discharge. A
      medication reconciliation project was begun in 2007 at an integrated health care
      system to (1) improve the accuracy of PAMLs within 24 hours of admission for
      patients admitted through the emergency department (ED) and (2) enhance patient
      education through telephone calls by pharmacists to the patients most at risk for
      adverse drug events (ADEs) or readmission. ACCURACY OF PAMLs: In the October 2007
      May 2008 period, RN-generated PAMLs were accurate 16% of the time versus 89% for
      the June 2008-December 2010 period, when they were generated by pharmacy
      technicians. Medication errors classified as having the potential to cause
      moderate or serious harm decreased from 13.17% to 1.50%. POSTDISCHARGE EDUCATION
      OF COMPLEX PATIENTS BY PHARMACISTS: By summer 2009, the Safe Med pharmacist
      program was fully staffed, thereby enabling the program to contact nearly 100% of
      the 10,174 patients meeting the Safe Med criteria from January 2009 through
      December 2010. When compared with historical controls, the Safe Med intervention
      was associated with a statistically significant reduction in 30- and 60-day
      readmissions, ADE-associated 30- and 60-day readmissions, and 30- and 60-day ED
      visits. CONCLUSIONS: ED-deployed pharmacy personnel can enhance the accuracy of
      PAMLs and may thereby reduce in-hospital ADEs. The postdischarge intervention by
      pharmacists with the most complex patients may reduce ADEs following hospital
      discharge. The interventions may compensate for discontinuities in care and
      lessen the attendant threats to patient safety.

PMID- 23130392
TI  - Reducing ventriculostomy-related infections to near zero: the eliminating
      ventriculostomy infection study.
AB  - Implementation of a standard protocol and use of antibiotic-coated ventricular
      catheters helped reduce EVD-related infections from 9.2% to almost zero at the
      University of Florida. This project demonstrated the success of creating a task
      force to identify areas of improvement, implement solutions, and monitor the
      outcomes.

PMID- 23130393
TI  - A history of and a vision for CMS quality measurement programs.

PMID- 23130394
TI  - Improving teamwork on general medical units: when teams do not work face-to-face.

PMID- 23130395
TI  - Converging worlds: high-tech security system installation + operation requires a
      team effort.

PMID- 23130396
TI  - Driving patient involvement.

PMID- 23130397
TI  - Art that works.

PMID- 23130398
TI  - Optimizing efficiency: new products put facility control and monitoring within
      easy reach.

PMID- 23130399
TI  - ASHE requests help for critical ICC hearings.

PMID- 23130400
TI  - Techniques for cleaning outside the box.

PMID- 23130402
TI  - Positive feedback: how ES departments can improve their HCAHPS scores.

PMID- 23130401
TI  - Current compliance: advice on recent electrical system code changes.

PMID- 23130403
TI  - [A resume of "organic"].

PMID- 23130404
TI  - [Soccer despite disability].

PMID- 23130405
TI  - [Child health and illness nursing: integrated into "early assistance"].

PMID- 23130407
TI  - [Cry babies].

PMID- 23130406
TI  - [The effect of massage and kangaroo care on stable premature infants].

PMID- 23130408
TI  - [Bullying: what victims can do].

PMID- 23130410
TI  - [15 day care centers nominated for the 2012 German Prevention Award].

PMID- 23130409
TI  - [Sepsis in pediatric intensive care patients].

PMID- 23130411
TI  - [Legal bases for the legitimacy of decisions in pediatric palliative care].

PMID- 23130412
TI  - [Consensus recommendations from Australia for nursing measures in sepsis and
      septic shock with a commentary from the German perspective].

PMID- 23130413
TI  - [Measures to insure compliance with immunosuppressive therapy in adolescents with
      kidney transplants].

PMID- 23130414
TI  - [Nursing scientists express their opinions on the proposed EU reform of nursing
      education].

PMID- 23130415
TI  - [Contribution of child rearing counselors to early interventions].

PMID- 23130416
TI  - [When the nose is stuffy starting in the fall].

PMID- 23130417
TI  - [Microorganisms and us: who is in charge?].

PMID- 23130418
TI  - [The changing epidemiology of sexually transmitted infections in Switzerland].
AB  - Sexually transmitted infections (STI), such as syphilis, gonorrhoea and
      infections caused by Chlamydia have been increasingly reported in Switzerland
      during the last decade. After having consistently decreased since the early 90s,
      reports of HIV infections were on the rise from 2000 to 2008. STIs are thus far
      from being controlled in Switzerland and their epidemiology has become more
      complex: different STIs circulate in different populations. The national program
      for HIV and STI 2011-2017 (PVNI) takes this challenge up and covers now the
      prevention, screening and treatment of all STIs. Primary care physicians,
      gynaecologists and specialists have an important role to play in provider
      initiated testing and counselling (PICT) and in the treatment of STIs.

PMID- 23130419
TI  - [Role of probiotics in the treatment and prevention of antibiotics-associated
      diarrhea].
AB  - Probiotics constitute an alternative to prevent or treat antibiotics-associated
      diarrhea (AAD). According to WHO, probiotics are "live microorganisms which, when
      administered in adequate amounts, confer a health benefit on the host". Recent
      meta-analyses, including adult and pediatric in- and outpatients, outlined the
      lack of good quality studies and of the lack of evaluation of side-effects. These
      meta-analyses showed a positive effect of probiotics in AAD, nevertheless without
      identifying patients who would benefit the most of them. Severe side-effects have
      been described in immunocompromised patients, those with abnormalities in their
      intestinal barrier, and those with central venous catheters.

PMID- 23130420
TI  - [Neurotoxic effects of antimicrobial agents].
AB  - Antimicrobial agents are occasionally responsible for significant neurological
      toxicity, the incidence of which is difficult to determine due to numerous
      confounding factors. It is nonetheless crucial to include this possibility in the
      differential diagnosis of any new or worsening neurological condition happening
      during antimicrobial treatment. Except for well described side effects
      (aminoglycoside ototoxicity) it is a rule out diagnosis and often necessitates a
      thorough metabolic and neurological work up. Once the diagnosis is strongly
      suspected, the therapeutic approach should always include the discontinuation of
      the offending agent, supportive measures and occasionally specific treatment.
      This article describes the wide possible neurological presentations and includes
      summary tables according to antimicrobial class.

PMID- 23130421
TI  - [Tick-borne encephalitis: first autochtonous case and epidemiological
      surveillance in canton Valais, Switzerland].
AB  - Tick-borne encephalitis (TBE, in French MEVE) is a viral disease usually
      transmitted to man through an infected tick belonging to the genus Ixodes. Every
      year about 135 cases of TBE are reported to the Swiss Federal Office of Public
      Health. Emerging in north-east of Switzerland in the seventies, endemic areas
      have been slowly spreading. Actually 18 cantons out of 26 have been reached. In
      the western part of Switzerland, spared until not long ago, new endemic foci are
      spreading toward the lake of Geneva and recently in Valais. The precise exposure
      history of human cases, as well as the evaluation of collected tick samples allow
      the detection of endemic foci which are discontinuous and of variable size. New
      and more efficient methods are needed to monitor the changing epidemiology of
      TBE.

PMID- 23130422
TI  - [Q fever: a cause of fever of unknown origin in Switzerland].
AB  - We describe two cases of Q fever in previously healthy women presenting with
      fever of unknown origin. The diagnosis was made after several days of
      investigations. Symptoms and signs of acute or chronic Coxiella burnetii
      infection are protean and non-specific. Q fever should be included in the
      differential diagnosis of fever of unknown origin and appropriate serologic
      studies should be done. We review the clinical presentation of Q fever. Use of
      serology for the diagnosis and the follow-up is discussed.

PMID- 23130423
TI  - [Resistant enterobacteria: explosion of extended-spectrum beta-lactamases].
AB  - During the past recent years, Enterobacteriaceae have supplanted Gram-positives
      in terms of frequent resistant bacteria seen in the outpatent setting. This
      change involves common opportunistic pathogens such as E. coli and K. pneumoniae.
      It is mainly due to the appearance and dissemination of extended-spectrum beta
      lactamases (ESBL), that hydrolyse penicillins and cephalosporins. Bacteria
      producing these enzymes are often also resistant to quinolones and trimethoprime
      sulfamethoxazole. This article, illustrated by a clinical case, presents the
      current epidemiology of ESBL-producing Enterobacteriaceae and the possible
      prevention measures and treatment options to fight the growing number of
      infections that they are causing.

PMID- 23130424
TI  - [Hikikomori is perhaps not what we would like it to be].

PMID- 23130425
TI  - [Black holes in white matter].

PMID- 23130426
TI  - [Do benzodiazepines cause dementia?].

PMID- 23130427
TI  - [By refusing the eldest's finger, we fail to seen the moon...].

PMID- 23130428
TI  - [Maize is herbicide and the rats are not well (1)].

PMID- 23130429
TI  - [Mecca 2012 against a backdrop of SARS menace].

PMID- 23130430
TI  - [Control of DRG. The arms race].

PMID- 23130431
TI  - Health situation analysis of Thai population 2010: implications for health
      education and health service reform.
AB  - BACKGROUND: Between 1990 and 2010, many national and international factors
      converged to both beneficially and antagonistically affect people's health and
      the Thai healthcare system. Moreover Thailand is moving to aged society and a low
      birth rates. OBJECTIVE: To analyze Thailand's health issues for baseline
      information for changing medical education, services and researches. MATERIAL AND
      METHOD: Information on illness of in-patients, out-patients and casualties came
      from hospitals nationwide and from hospitals withdrawals from the three health
      insurance schemes in fiscal 2010. The data included 96% of the population.
      Research literature was also extensively reviewed. The data were analyzed by age
      groups and burdensome diseases. RESULTS: Out-patients were treated 326,230,155
      times and in-patients 6,880,815 times at Community Hospitals (44%), Provincial
      Hospitals (22%), Central or University Hospitals (26%) and Private Hospitals
      (8%). Infants and elderly were the patients most commonly treated in hospital.
      Among pediatric patients, perinatal disease, intestinal infection, respiratory
      tract infection, injury and poisoning and teenage pregnancy predominated; while
      among adults, it was accident, non-communicable and chronic disease. CONCLUSION:
      Thailand is faced with the dual burden of infection and non-communicable
      diseases. Risky behavior and changing social structure are underlined this
      epidemiological transition. Medical schools and health service systems need to be
      recalibrated to response proactively to these challenges.

PMID- 23130432
TI  - Current challenges in reducing neonatal morbidity and mortality in Thailand.
AB  - BACKGROUND: Information on neonatal mortality and burden of illness during the
      neonatal period is an essential guide for prioritizing interventions for solving
      health problems and allocating resources. OBJECTIVE: To evaluate the burden of
      diseases and the current health situation among Thai neonates under the Universal
      Health Insurance Coverage Scheme. MATERIALS AND METHOD: The number of admissions
      according to mortality, length of hospital stay and cost of hospital charges
      during the neonatal period was analyzed. RESULTS: There were 638,795 live births
      according to the data extracted from the three healthcare schemes supporting
      universal healthcare' in Thailand, which is lower than the data from the Health
      Information Unit of the Bureau of Health Policy and Strategy at the Ministry of
      Public Health. The neonatal death rate was 3.98 per 1,000 live births comprising
      58.9% of all infant deaths. Major proportion of neonatal deaths (700%) occurred
      in early neonatal period and 43% of which occurred within the first two days of
      life. The leading causes of neonatal deaths were prematurity, respiratory
      problems, congenital malformation, birth asphyxia and infection. The most
      prevalent diagnosis for admissions was neonatal jaundice, disorders related to
      short gestation, respiratory disorders and neonatal infection. CONCLUSION: More
      investment is required to improve education and implement health interventions
      that can be integrated into existing health systems for better neonatal outcomes.

PMID- 23130433
TI  - Thai infant health situation: essential medical information for family centered
      care.
AB  - BACKGROUND: The family-centered care requires reliable information on morbidity,
      mortality and related health problems to educate the responsible families.
      OBJECTIVE: To explore diseases and deaths of infants aged 29 days-12 months under
      the 2010 Universal Health Insurance in Thailand. MATERIAL AND METHOD: As per
      Sutra et al in 'Health situation analysis of Thai population 2010. The data
      included in the analysis were numbers and percents of primary diagnosis of each
      visit in the outpatient department (OPD), admitted cases and infant death. Other
      health related issues were also retrieved from the existing sources of health
      information at country level. RESULTS: The infants aged 29 days-12 month had
      9,721, 266 OPD visits including factors influencing health (69.6%), respiratory
      infections (16.3%), Intestinal infection (2.4%) and other diseases (11.7%). The
      admitted cases commonly had respiratory infections (47.5%), intestinal infections
      (23.4%), other infections (4.8%) and congenital malformation (2.8%). The three
      most common causes of hospital deaths were perinatal conditions (25.2%),
      congenital malformation (21.4%) and respiratory infection (18.5%). There were
      also neonatal problems of low birth weight and iodine deficiency. CONCLUSION: The
      infectious diseases and perinatal health problems were the main issues for family
      education in the family centered care to reduce the burden of diseases and infant
      death.

PMID- 23130435
TI  - The health situation among Thai elementary school-age children: 2010.
AB  - BACKGROUND: The school years are a crucial time in the development of the basic
      life skills necessary for learning in the various and different fields to be
      encountered in life, as well as for developing and acquiring the knowledge,
      skills and attitudes necessary to establish and maintain a healthy lifestyle. In
      general, elementary school-age children rarely present at health service centers
      but may nevertheless have health problems that affect their ability to learn.
      OBJECTIVE: To analyze the health situation among elementary school-age children
      in Thailand, for the creation of baseline information to serve as an evential
      basis for making recommendations for adjusting the medical education curriculum
      and for improving health service provision. MATERIAL AND METHOD: To analyze
      nationwide, hospital data, for the morbidity and mortality of children age 6-12
      years in fiscal year 2010. RESULTS: Respiratory infections represented the
      leading cause for out-patient visits-approximately one-fifth. Respiratory
      infections were also a significant cause for admissions (21.6%), followed by
      dengue hemorrhagic fever (14.8%), injury and poisoning (11.3%), disease of
      digestive system (11.1%) and intestinal infection (10.3%). The leading causes of
      death were injury and poisoning (22.7%), followed by neoplasm (14.4%), other
      infection (13.5%) and respiratory infection (12.6%). Overall, about 50-60% of the
      causes of admissions and of deaths were due to infectious diseases and injury &
      poisoning. CONCLUSION: Infectious diseases and injury & poisoning were the major
      physical illnesses among school-age children. Notwithstanding, there were other
      health issues-including nutrition, growth & development, mental health &
      psychosocial problems-that need to be recognized and addressed in order to ensure
      the health and well-being of school-age children in Thailand.

PMID- 23130434
TI  - Health situation analysis of Thai children aged 1-5 years in 2010: implications
      for health education and health service reform.
AB  - BACKGROUND: To make the world fit for children is a task necessarily involves all
      organizations working with children. The real health situation will be useful for
      strategic planning for them. OBJECTIVE: To emphasize Thailand's health burdens of
      children between 1 and 5 years in 2010. MATERIAL AND METHOD: The authors analyzed
      the fiscal 2010 data from the three health insurance schemes from hospitals
      nationwide for information on: out-patient and in-patient visits, common
      illnesses of Thai children between 1 and 5 years, lengths of stay, hospital
      charges and deaths. Most (96%) of the population was represented in this data.
      RESULTS: Respiratory infection was the most common admission (225,183 times)
      while intestinal infection was the second (83,293 times). Respiratory infection
      was the second most common for an out-patient visit (7, 387,132 times = 23.6%)
      after other factors influencing health (17,384,963 times = 55.5%). The most
      common causes of death were injury and poisoning (178 patients) and respiratory
      infection (175 patients). Pneumonia required the most budget and resulted in the
      longest stays. Among accidents, accidental drowning and submersion caused the
      most deaths. CONCLUSION: Respiratory infection, pneumonia, intestinal infection,
      injuries, poisoning and accidental drowning were the most common health burdens
      among children between 1 and 5 years of age.

PMID- 23130436
TI  - Thailand's adolescent health situation: prevention is the key.
AB  - BACKGROUND: Adolescence is generally a period of good physical health, but future
      health problems may begin at this age due to exposure to risk factors for
      diseases. OBJECTIVE: To analyze the health situation of adolescents (age 13
      18years) in Thailand in order to derive guidance for the refinement and
      calibration of the medical curriculum and enhance health service provision to
      adolescents. MATERIAL AND METHOD: National data from Thailand's 3 major health
      care systems, regarding; the causes of out-patient visits, in-patient admissions
      and deaths in the fiscal year 2010 were analyzed. RESULTS: The leading causes of
      out-patient visits were (1) factors influencing health (2) respiratory infections
      (3) diseases of the digestive system (4) injury and poisoning and (5) external
      causes of morbidity and mortality. The leading causes of admissions were (1)
      pregnancy (2) injury and poisoning and (3) arthropod-borne viral fevers. The
      leading causes of hospital deaths were (1) injury and poisoning (2) neoplasms and
      (3) other infections. CONCLUSION: The majority of the causes of morbidity and
      mortality were related to psychosocial factors and engagement in high risk
      behaviors.

PMID- 23130437
TI  - Children in difficulties.
AB  - BACKGROUND: Children in difficulties are characterized by: chronic neglect;
      disability; physical, emotional or sexual abuse; HIV or one/both parents with HIV
      and/or limited socio-economic opportunities. OBJECTIVE: To review the current
      situation by reviewing the incidence of problems affecting children and exploring
      both potential short-/long-term strategies, including the role of pediatricians.
      MATERIAL AND METHOD: The authors reviewed the incidence and situations of
      children in difficulties, did a synthesis of guidelines and made recommendations.
      RESULTS: The fundamental causes of difficulties include: failed macro-economic
      policies; inadequate and inaccessible education system; and weakness of the
      family unit, which is associated with: separation and divorce; violence between
      partners and/or toward their children; neglect and abandonment; inappropriate
      child-rearing; and child exploitation, including trafficking. CONCLUSION: GOs and
      NGOs need to work collaboratively for child protection. Pediatricians can play a
      vital role in strengthening the family (a) by providing timely strategic,
      informal education for parents on healthy child-rearing (b) by being attuned to
      signs, symptoms and attitudes of children in difficulties from childhood through
      adolescence and (c) by working interactively with children/teens, their families,
      teachers and communities. Medical schools need to revise the curricula to include
      these crucial roles for pediatricians in child and family advocacy.

PMID- 23130438
TI  - Disease patterns among Thai adult population: an analysis of data from the
      hospitalization National Health Insurance System 2010.
AB  - BACKGROUND: Disease pattern is an important informational tool used by
      policymakers in setting priorities, strategies and allocating budgets to address
      the precursors or causes of health problems. OBJECTIVE: To analyze the common
      diseases in the adult population using in-patient information from the three
      health insurance coverage schemes in the fiscal year 2010. MATERIAL AND METHOD:
      The authors analyzed the data on in-patients with 23 major disease groups as per
      ICD-10 coding. The data were analyzed to obtain the number of patients, number of
      admissions, number of hospital mortalities, mortality rates and length of
      hospital stays. RESULTS: The total number of adult in-patients was 3,876,792
      presenting for admission 4,863,935 times. Infectious and parasitic diseases were
      the most common causes of admission. Diseases of the circulatory system resulted
      in the highest number of mortality rate (8.72%). Intracerebral hemorrhage,
      neoplasm, septicemia, liver failure, coronary heart disease, HIV/AIDS, status
      epilepticus, pneumonia, accidents and acute renal failure were the top ten
      diseases with a high mortality rate. CONCLUSION: The review indicated
      communicable diseases are the most common disease group although non-communicable
      diseases were also important because of their high mortality rate.

PMID- 23130439
TI  - Health situation analysis of hospitalized Thai older persons in the year 2010.
AB  - BACKGROUND: Thailand has reached an ageing society on account of demographic
      transitions. Hospitalized elders are susceptible to having detrimental
      consequences in many aspects. Understanding the situation regarding elders being
      hospitalized would help allied-healthcare workers to focus and take necessary
      action on particular issues. OBJECTIVE: To demonstrate the admission rate of
      elders, common causes of hospitalization and their mortality rates. MATERIAL AND
      METHOD: Information on illness of inpatients and casualties came from hospitals
      nationwide and from hospitals withdrawals from the 3 health insurance schemes in
      fiscal 2010. The data included 96% of the population. The data were analyzed by
      age groups and burdensome diseases. RESULTS: Elders posed the highest rate of all
      hospitalization (24.3/100 older persons) and the proportion increased with age.
      The top three common causes for hospitalization were diseases of respiratory
      tract (13%), circulatory (12%) and digestive system (11%). Mortality rates were
      highest in elders with pneumonia (129.7/100,000 persons). CONCLUSION: Older
      hospitalization was the highest for all hospitalization ages. Common causes for
      hospitalization are partly the consequences of modifiable factors. Thus,
      healthcare providers require extensive effort to enhance education and training
      to allied-healthcare workers regarding preventive and early diagnosis strategies
      to those with frequent illnesses.

PMID- 23130440
TI  - Burden of acute lower respiratory infection in children in Thailand in 2010: have
      we achieved the national target in under-five morbidity and mortality?
AB  - BACKGROUND: National reports indicate that morbidity and mortality from pneumonia
      among Thai children has decreased dramatically since the turn of the millennia;
      notwithstanding, pneumonia remains the leading cause of admission and death in
      Thai children under five years of age. OBJECTIVE: To assess the burden and
      pattern of acute lower respiratory infection in under-fives in Thailand from the
      health data in 2010. MATERIAL AND METHOD: Information on respiratory infection
      using the ICD10: J09-J22 was evaluated for the number of OPD visits, admissions,
      mortality, monthly incidence and co-morbidities of the mortality. RESULTS: 73% of
      all OPD visits with ALRI were in under-fives: one-fourth of whom required
      hospitalization. Pneumonia is the leading cause of both admissions and mortality
      (3.22% and 11.29/100,000 population for this age group, respectively). The
      highest mortality was in the first year of life (39/100,000). One-fourth of the
      children (168/639) died within 24 hours of admission and septicemia was the most
      common co-morbidity. CONCLUSION: The respective morbidity and mortality of
      pneumonia in under-fives fell far short of national targets. To achieve these
      targets, many key aspects are needed; such as, strengthening the knowledge of
      healthcare personnel, the cost-effectiveness researches on the causative organism
      detection and the expanding coverage of the preventable-vaccine.

PMID- 23130441
TI  - Burden of acute, persistent and chronic diarrhea, Thailand, 2010.
AB  - BACKGROUND: The incidence of diarrhea in Thai children under five years of age
      increased over the last decade while mortality dramatically decreased. To
      evaluate the effectiveness of MCH services under Universal Coverage Schemes,
      health outcomes should be performed. OBJECTIVE: To assess the burden and pattern
      of childhood diarrheal diseases in Thai children under five. MATERIALS AND
      METHOD: The information on Intestinal Infectious Diseases ICD10: A00-A09 was
      divided into two groups: 1. Infectious diarrhea: A04, A05, A08, A09 and 2.
      Dysentery: A02, A03. The authors investigated the number of OPD visits, IPD,
      mortality, length of hospital stay and co-morbidity of severe cases. RESULTS: The
      burden of diarrhea was: 3.7 million (1:1) episodes, 756,552 OPD visits (1:5),
      124, 403 IPD admissions (1:30), 202 (1:18,460) persistent diarrhea and 48 (1:77,
      685) deaths. Diarrheal incidence had two peaks: cool season and early rainy
      season. Admissions lasted a collective 309,398 days. Diarrhea was persistent in
      202 episodes (1.6 per 1,000 admissions) and the associated factors included: age,
      sepsis, anemia, chronic diseases, malnutrition and HIV. The risks for diarrhea
      related mortality included: infant, septicemia and dehydration. CONCLUSION: The
      incidence of diarrhea was higher than expected albeit mortality was low. The
      mortality rate was associated with age under one year persistent diarrhea,
      septicemia, chronic and underlying diseases.

PMID- 23130442
TI  - Dengue mortality in patients under 18 years old: an analysis from the health
      situation analysis of Thai population in 2010 project.
AB  - BACKGROUND: Dengue is an important cause of morbidity and mortality in tropical
      and subtropical regions of the world. In Thailand, there has been no detailed
      research on mortality in children in terms of duration of admission and
      associated complications in the cases that died. OBJECTIVE: To assess the burden
      of dengue in Thailand in 2010 and to analyze the complications in patients aged
      under 18 years who died. MATERIAL AND METHOD: The authors described the mortality
      and complications of dengue fever and dengue hemorrhagic fever in patients under
      18 years old using the information from the Health Situation Analysis of the Thai
      Population 2010 Project. RESULTS: In 2010, the overall mortality of dengue in all
      age groups and in patients aged under 18 years were 0.3 and 0.6/ 100,000,
      respectively. The mortality rate was highest among children aged 6-12 years
      (0.8/100,000). Among the 8 children with dengue fever that died, the 2 most
      common complications were fluid electrolyte and acid-base imbalance and
      disseminated intravascular coagulation (DIC). The common complications among the
      91 cases with dengue hemorrhagic fever that died included fluid electrolyte and
      acid-base imbalance, hepatic failure, respiratory failure, bacterial infection,
      DIC and renal failure. CONCLUSION: Early diagnosis, careful management of fluid
      therapy, awareness of hepatic and renal impairment and early treatment of co
      infection should decrease mortality of dengue hemorrhagic fever

PMID- 23130443
TI  - Unintentional injury among Thai children and adolescents in 2010.
AB  - BACKGROUND: Unintentional injury has been identified as a public health problem
      in Thailand as it is the leading cause of death among both children and
      adolescents. OBJECTIVE: To explore the number of admissions by unintentional
      injury and cause(s) among Thai children and adolescents in 2010. MATERIAL AND
      METHOD: Data on the number of admissions by unintentional injury in the fiscal
      year, 2010, were derived from hospitals nationwide as well as the three health
      insurance schemes. Data on Thai children and adolescents (0-18 years) was
      collected between October 1, 2009 and September 30, 2010. The coding for
      underlying cause(s) of unintentional injuries and death were done using the
      International Classification of Diseases, 10th edition. RESULTS: A total of
      118,323 unintentional injuries were reported. The majority of patients were male
      and falls were the major cause of unintentional injuries (27,139 admissions;
      22.94%) followed by motorcycle injuries (20,499 admissions; 17.32%). Accidental
      drowning and submersion was the major cause of death in the present study,
      followed by lightning strikes and accidental threats to breathing (i.e., choking
      and suffocation). CONCLUSION: The current study revealed that falls were the
      major cause of unintentional injury and accidental drowning and submersion the
      major cause of death.

PMID- 23130444
TI  - Childhood neoplasms: analysis of Thai children 2010.
AB  - BACKGROUND: Between 1990 and 2010, many national and international factors
      converged to both beneficially and antagonistically affect people's health as
      well as the Thai healthcare system. Among these were: a falling birth rate in
      Thailand and a gradual decline in poverty-related diseases. Cancer becomes the
      most common cause of death. OBJECTIVE: To analyze Thailand's childhood neoplasm
      issues for baseline information for changing medical education, services and
      research. MATERIAL AND METHOD: Information on the illnesses of in-patients, out
      patients and casualties was based on hospital withdrawals nationwide from the
      three health insurance schemes in the fiscal year 2010. The data, which included
      96% of the population, were analyzed by age groups and burden of neoplasm
      disease. RESULTS: The children with neoplasms were treated 127,597 times at
      outpatient departments (OPD) and 19,159 times at inpatient departments (IPD) at
      community hospitals (4.3%), provincial hospitals (8.50%), regional or university
      hospitals (86.1%) and private hospitals (1.1%). Malignant neoplasms of lymphoid
      hematopoietic and related tissues were the most common in both IPD and OPD
      settings, which resulted in the highest cost of treatment. Tumors of the central
      nervous system were associated with the highest cost. The mean length of stay for
      all patients with neoplasm was 7.85 days. CONCLUSION: Sufficient budget should be
      allocated to the more heavily frequented treatment center Specific and better
      care, national treatment protocols for each type of childhood cancer (including
      palliative care) should be developed to improve the treatment outcomes and/or the
      quality of life. Medical schools and health service systems need to be
      recalibrated to respond proactively to these changes being experienced by the
      healthcare system.

PMID- 23130445
TI  - Adolescent pregnancy: Thailand's national agenda.
AB  - BACKGROUND: Unintended pregnancy during adolescence can have profound effects on
      adolescents, their parents and family, the child and the country's developing
      population. OBJECTIVE: To analyze the adolescent pregnancy situation in Thailand
      in order to provide data and suggestions for refining the nation's medical
      curricula and enhancing health services for adolescents. MATERIAL AND METHOD:
      National data from Thailand's 3 major health care systems, regarding; adolescent
      pregnancy complications, deliveries, outcomes and deaths in the 2010 fiscal year
      were analyzed and compared to women 20-34 years of age. RESULTS: There were
      80,523 adolescent pregnancies, comprising 25.9% of all pregnancies. The pregnancy
      rate for 15-19 year-olds was 33.4 per 1,000 and abortion was the outcome in
      14.4%, (18.0% of all abortions). The adolescent birth rate was 28.7 in women 15
      19 years of age-on average, there were 188.8 adolescent deliveries per day.
      Adolescents gave birth to 37.2% of all preterm infants: the preterm birth rate
      was significantly greater than in women in the optimum reproductive age. Most
      deliveries were spontaneous vertex deliveries with lower complications and
      mortality rates than for women in the optimum reproductive age. CONCLUSION:
      Unintended pregnancy can have profound effects on adolescent parents, their
      parents and families, the child and the country's developing population. It
      should, therefore, be considered a major public health problem that warrants
      immediate intervention at the national level.

PMID- 23130446
TI  - Burden of human immunodeficiency virus (HIV) infection in hospitalized Thai
      adults: an analysis of data from the National Health Insurance System 2010.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) infection continues to be a major
      health problem worldwide. Whether several intervention programs are successful
      enough to ameliorate the significant hospitalization burden created by these
      patients is not known. OBJECTIVE: To analyze the burden of HIV infection on
      patient-hospitalization and death in the adult population using in-patient
      information from the three health insurance coverage schemes from the fiscal year
      2010. MATERIAL AND METHOD: The authors analyzed the data on in-patients with ICD
      10 coding B20-B24 HIV disease to obtain the admission and mortality rate, length
      of hospital stay and hospital charges. RESULTS: The admission rate among adult
      HIV-infected patients was 91.8 times per 100,000 adult population. The most
      common age group affected by the disease was the 26-40 year-olds (59%). The most
      common condition causing hospitalization was opportunistic infection (83.6%), of
      which tuberculosis was the highest. The mortality rate was 10.3% and increasing
      with age. AIDS-related symptoms, malignancy and opportunistic infections were the
      major impacts on mortality. CONCLUSION: HIV/AIDS still constitutes a major
      disease burden among the adult Thai population. Increased public awareness and
      prevention and access to early HIV diagnosis and treatment could be key factors
      for lowering the burden of disease and improving clinical outcomes.

PMID- 23130447
TI  - Coronary artery disease in the Thai population: data from health situation
      analysis 2010.
AB  - BACKGROUND: The rate of cardiovascular disease marked by coronary artery disease
      (CAD) is increasing in low-middle income countries including Thailand. The burden
      of CAD will have a significant impact on the healthcare system and the national
      budget. OBJECTIVE: To identify the CAD-related hospitalization rate over one
      year; to determine in-hospital mortality in various subgroups of patients with
      CAD and to examine the hospitalization costs of patients with CAD. MATERIAL AND
      METHOD: The data were extracted from in-patient discharge forms from the three
      main health insurance schemes in Thailand for the fiscal year 2010 (October 1,
      2009 to September 30, 2010. The data included the three major health insurance
      schemes which provided coverage for about 62 million people (96% of the
      population). Data regarding coronary artery disease using the ICD-10 (I20-angina,
      I21-acute myocardial infarction (AMI) and I25-chronic ischemic heart disease)
      were extracted and analyzed for number of admissions, mortality rate, length of
      hospital stay and hospital charges. RESULTS: In 2010, the total admissions of
      patients with coronary artery disease were 22,507. The most common presentation
      of CAD was angina pectoris (10,822 admissions)followed by AMI (6,391 admissions)
      and chronic ischemic heart disease (5,294 admissions). The respective in-hospital
      mortality rates in patients admitted with AMI, chronic ischemic heart disease and
      angina pectoris were 11.3%, 2.9% and 0.7%. CONCLUSION: Thailand is entering a
      period of epidemiologic transition marked by an increase of cardiovascular
      disease and hospital expenses dominated by cardiovascular disease. Information on
      the burden of CAD--indicates a need to improve health care system.

PMID- 23130448
TI  - Characteristics and burden of hospitalization because of intentional self-harm:
      Thai national, hospital-based data for 2010.
AB  - BACKGROUND: There is a paucity of data on intentional self-harm and suicide in
      Thailand. It is crucial to re-evaluate the burden and health outcomes. OBJECTIVE:
      To measure the character and burden of acts of intentional self-harm in the Thai
      hospitalized population. MATERIAL AND METHOD: Acts of intentional-self harm were
      categorized using ICD 10 classification. All of inpatient-related data were
      analyzed using SPSS 17. RESULTS: Overall intentional self-harm in 2010 led to
      24,924 hospitalizations and 854 deaths; an incidence of 35.6/100,000 people with
      the highest level in two age groups: 18-25 and 26-40 year-olds. Self-poisoning
      (89%) was the most common method and pesticide was the leading used chemical
      agents. The total cost of treatment was 149,672,190 baht and the mean length of
      stay was 2.9 +/- 6.7 days. The mortality rate increased as the population got
      older with the highest rate being 10.6% for 70-79 year-olds. In 33.8% of cases,
      psychiatric co-diagnosis were found with anxiety disorders was the leading
      comorbidity. CONCLUSION: The incidence of intentional self-harm was medium to
      high, compared to other East Asians countries. Self-poisoning by exposure to
      pesticides was the most common self-harm method. Age over 60 had the highest
      mortality rate. Having a psychiatric co-diagnosis was common.

PMID- 23130449
TI  - Epidemiology of assault-related hospitalizations in Thailand in the fiscal year
      2010: comparison between with and without psychiatric disorder.
AB  - BACKGROUND: Assault is a leading cause of injury and death; however little is
      known regarding the psychiatric epidemiology of assault-related hospitalizations
      (ARH) in Thailand. OBJECTIVE: To analyze the epidemiological data of ARH in
      Thailand for the fiscal year 2010 and to compare the epidemiology of ARH between
      with and without psychiatric disorder MATERIAL AND METHOD: The data analyzed were
      from the annual reports for the fiscal year 2010 (October 1, 2009-September 30,
      2010), on every kind of hospitalization reimbursed by the Universal Health
      Coverage System, the Social Welfare System, and the Civil Servant Medical
      Benefits Scheme, altogether provided medical coverage for more than 96% of the
      Thai population. The information on ARH (X85-Y09: ICD-10 version for 2010) and
      comorbid psychiatric disorder(s) (F00-F99) were extracted. Number of in-patient
      hospitalizations by sex, age, geographical region, month, hospital charges,
      length of hospital stay (LOS) and mortality rate (MR) were analyzed. Frequencies
      (percentages) of ARH and subgroups were reported. RESULTS: The national ARH care
      cost was 0.98% of the overall national in-patient care expenses (88,964 million
      Baht). The rate of ARH was 0.72 of every 100 hospitalizations or 7.74
      incidents/100,000 general population. Assaults leading to hospitalizations
      frequently occurred among males (80.86%); in 25-39 year-olds (35.60%), 40-59 year
      olds (22.85%); by sharp object (29.44%), blunt object (24.40%) and bodily force
      (23.71%); in the Central (39.48%) and Northeast region (31.16%). There was a tri
      modal monthly peak distribution: April (11.12%), December (9.45%) and October
      (8.90%). A minority i.e. 0.4% (male to female ratio of 4.22:1) of ARH had a
      concomitant psychiatric disorder(s): the most frequent being 'mental and
      behavioral disorders due to psychoactive substance use' (66.54%) followed by
      'schizophrenia, schizotypal and delusional disorders' (14.230%). The MR of ARH
      with and without concomitant psychiatric disorder was 1.03% and 0.30%,
      respectively. The LOS of overall ARH was 5.15 +/- 12.41 days, min-max was 1-568
      days and the mode was 1 day. The LOS of ARH with/without psychiatric disorder was
      5.2 +/- 12.4 vs. 3.7 +/- 7.5 days. The expenses paid for ARH with/without
      psychiatric disorder was 75,811,383.40 Baht vs. 791,214,659.90 Baht. CONCLUSION:
      Assault accounted for 0.72 hospitalization of every 100 hospitalizations and 7.74
      times/100,000 population. A fraction (0.04%) of ARH had concomitant psychiatric
      disorder(s): most frequently psychoactive substance use disorders followed by
      schizophrenia and related psychosis.

PMID- 23130450
TI  - Analysis of eye health in the Thai population.
AB  - OBJECTIVE: To assess national eye health as a baseline for improving medical
      education, services and research. MATERIAL AND METHOD: Information on eye illness
      among out- and in-patients was based on hospital claims from the three national
      health insurance schemes in 2010. The data were analyzed by age groups. RESULTS:
      In 2010, 4,982,025 out-patient visits and 187,080 in-patient admissions were
      reported. The five most common outpatient eye conditions were disorders of the
      (1) conjunctiva (H10-H13) (2) eyelid, lacrimal system and orbit (H00-H06) (3)
      lens (H25-28) (4) sclera, cornea, iris and ciliary body (H15-H22) and (5)
      glaucoma (H40-H42). The five most common inpatient eye diseases were (1)
      disorders of lens (H25-H28) (2) conjunctiva (H10-H13) (3) sclera, cornea, iris
      and ciliary body (H15-H22) (4) choroid and retina (H30-H35) and (5) glaucoma (H40
      H42). CONCLUSION: Information on the most frequent eye diseases-including the
      types and frequency of high risk conditions, the diseases causing the most impact
      on vision and resulting in the highest health expenditures-will be used to (a)
      revise the curricula for medical education (b) to improve eye care services and
      (c) to improve access to data for research themes tailored to local and national
      needs.

PMID- 23130451
TI  - Management of cataract in the Thai population.
AB  - OBJECTIVE: To analyze the types of cataracts, surgical procedures, hospital
      charges and length of stays among the Thai population. MATERIAL AND METHOD:
      Information on cataracts among out- and in-patients in the fiscal year 2010 was
      retrieved from the databases of the three main national health insurance schemes.
      The data were analyzed according to the types of cataract, surgical procedures,
      hospital charges and length of stays. RESULTS: There were 654,352 out-patient
      visits and 146,994 in-patient admissions in the fiscal year 2010. The number of
      cataract patients was greatest among 61-80 year-olds. Senile cataract was the
      most frequent type of cataract (97.11%) followed by traumatic (0.59%), infantile,
      juvenile and pre-senile (0.45%), complicated (0.15%) and drug-induced (0.02%).
      Phacoemulsification with intraocular lens implantation was the most common
      surgical procedure used to restore vision among the elderly (83.07%). The average
      health expenditure for cataract was 18,527 baht and length of hospital stay 2.35
      days. CONCLUSION: Cataracts and their management in the Thai population were
      analyzed. For health economic reasons, all cataract surgeries should be on an out
      patient basis unless otherwise approved. Prospective studies should be designed
      to assess the relevant data on specific cataracts and the associated risk
      factors.

PMID- 23130452
TI  - The burden of head and neck cancers in Thailand.
AB  - OBJECTIVE: To determine the overall burden of disease vis-a-vis head and neck
      cancers in Thailand, as indicated by visits to healthcare units, admissions for
      treatment and expenditures at all levels of the healthcare delivery system.
      MATERIAL AND METHOD: A descriptive study was conducted by retrieving and
      analysing data for the fiscal year 2010 from the National Health Security Office
      (NHSO) and the Social Security Office, Thailand and from in-patient data of the
      Civil Servants Benefit System from the Comptroller General's Department. RESULTS:
      In 2010, there were 167,199 visits to outpatient departments (OPDs) and 26,012
      admissions to hospital (IPD) for diagnosis and treatment of head and neck
      cancers. The most common diagnosis for visits to OPD and admission to IPD was
      oral cancer (28.2% and 25%, respectively). The mean length of hospital stay was 9
      days. About half of admissions took place in the central region. The hospital
      charges totalled 691 million Baht (US$ 21.8 million), or an average of 26,556
      Baht (USS 838) per admission. CONCLUSION: Since a relatively high volume of
      hospital visits was found, there is an urgent need to train sufficient numbers of
      specialists in the field of head and neck cancer treatments to provide efficient
      healthcare.

PMID- 23130453
TI  - Hospitalized incidence and outcomes of upper gastrointestinal bleeding in
      Thailand.
AB  - BACKGROUND: Upper gastrointestinal bleeding (UGIB) is a common emergency
      gastrointestinal problem which has substantial mortality and health care
      resources use. The nationwide basic information on UGIB is not available in
      Thailand. OBJECTIVE: To identify the hospitalized incidence, outcomes and
      hospitalization cost of patients who presented with UGIB in Thailand. MATERIAL
      AND METHOD: Information on illness of in-patients from hospitals nationwide was
      retrieved from three major health schemes database in fiscal year 2010. RESULTS:
      The hospitalized incidence rate of UGIB was 166.3 admissions per 100,000
      populations and the hospitalized incidence rate of non-variceal upper
      gastrointestinal bleeding (NVUGIB) and variceal bleeding were 152.9 and 13.5
      admissions per 100,000 populations respectively. Endoscopic procedure was
      undertaken in 27.6% of NVUGIB admissions and 80.7% of variceal bleeding
      admissions. The in-hospital mortality rate, hospitalization cost and length of
      stay were higher in variceal bleeding patients compared with NVUGIB patients.
      CONCLUSION: UGIB is an important emergency gastrointestinal problem which has
      significant mortality and substantial health care resources consumption.

PMID- 23130454
TI  - Cost of colorectal cancer care in hospitalized patients of Thailand.
AB  - BACKGROUND: Colorectal cancer incidence rate is high and expected to increase in
      Thailand. But it is a preventable and curable disease if found in the early stage
      of development. The overall data regarding admission rates and healthcare cost in
      Thai patients are lacking. OBJECTIVE: To identify admission rates and healthcare
      cost of colorectal cancer. MATERIAL AND METHOD: Information on illness of
      inpatients and casualties came from hospitals nationwide and from hospital
      withdrawals from the 3 health insurance schemes in fiscal 2010. The data included
      96% of the population and were analyzed by age groups, hospital level and
      insurance schemes in patients with colorectal cancer. RESULTS: Colorectal cancer
      occurred in 45,692 of all admissions, contributing to admission rates of 98.5 per
      100,000 persons. These figures increased with age. The highest admission was
      found in the central region including Bangkok (43%) followed by the northeast
      region (23%). The average hospital charges per admission in three insurance
      schemes groups: government welfare, social welfare and universal coverage were
      64,241, 49,490 and 28,588 Baht, respectively CONCLUSION: Admission rates showed
      that colorectal cancer increased with age. The highest rate was observed in sixty
      years and older The hospital charges were extensive, especially in those on the
      government welfare scheme. Thus, screening programs, cost-effective analysis of
      treatment modalities and treatment protocol for the elderly should be examined.

PMID- 23130455
TI  - Lung cancer in hospitalized patients of Thailand.
AB  - OBJECTIVE: To identify admission rates, treatments and healthcare cost of lung
      cancer MATERIAL AND METHOD: Information on illness of inpatients and casualties
      came from hospitals nationwide and from hospital withdrawals from the 3 health
      insurance schemes in the fiscal year 2010. The data included 96% of the
      population and were analyzed by age groups, hospital levels, treatment and
      insurance schemes in patients with lung cancer. RESULTS: Lung cancer occurred in
      27,896 of all admissions, contributing to admission rate of 60 per 100,000
      persons. The admission rates were markedly increased in male more than 60 years
      old. The majority of treatments were palliative care 61.38%, chemotherapy 36.81%.
      The average length of stay and hospital charges in three insurance schemes
      groups: government welfare, social welfare and universal coverage were 40,571.29
      Baht/9.86 days, 43,342.54 Baht/8.24 days and 17,897.75 Baht/6.08 days,
      respectively. CONCLUSION: Admission rates showed that lung cancer increased with
      age. The highest rate was observed in more than 60 years old. The window gap in
      hospital charges and length of stay in three insurance schemes are interesting.
      Thus, analysis of treatment protocol should be examined.

PMID- 23130456
TI  - Patterns of chemotherapy usage in hospitalized breast cancer patients.
AB  - BACKGROUND: Breast cancer is the leading cancer in Thai women. Systemic
      chemotherapy is one of the main treatment options in both adjuvant and metastatic
      disease. Patterns of chemotherapy usage and hospital cost data are lacking.
      OBJECTIVE: To identify overall admission rate, chemotherapy admission and
      hospital cost data of breast cancer patients. MATERIAL AND METHOD: Information on
      illness of inpatients and casualties came from hospitals nationwide and from
      hospital withdrawals from the three health insurance schemes in the fiscal 2010.
      The data included 96% of the population. The data were analyzed by age groups,
      regions, hospital levels and insurance schemes in breast cancer patients.
      RESULTS: Admissions from breast cancer occurred for 35,490 in the year 2010.
      Admissions for systemic chemotherapy accounted for 53.1% of all breast cancer
      admissions and accounted for 17.3% of all admissions for chemotherapy. Most of
      chemotherapy admissions were in tertiary care hospital level. Mean length of stay
      for chemotherapy in breast cancer was 2.33 days compared to 5.30 days in other
      cancers. Mean hospital charge for chemotherapy for breast cancer was 13,904 THB
      compared to 33,693 THB for other cancers. The mean hospital charge three
      insurance schemes groups: government welfare, social welfare and universal
      coverage were 33,096, 19,932 and 9,599 THB, respectively. CONCLUSION: Admission
      rate for chemotherapy in breast cancer was not high. The cost of chemotherapy in
      each admission in breast cancer is nearly 50% lesser than chemotherapy for other
      cancers. Thus, generic drugs usage and outpatient administration of chemotherapy
      should be encouraged.

PMID- 23130457
TI  - The impact and disease burden of thalassemia in Thailand: a population-based
      study in 2010.
AB  - BACKGROUND: Thalassemia is a common genetic disease in Thailand. However, current
      data on the impact and disease burden of thalassemia in Thailand remains limited.
      OBJECTIVE: To determine the admission rate, OPD visit rate, mortality rate,
      hospital cost, length of hospital stay, blood transfusion rate and major
      complications rate in patients with thalassemia. MATERIAL AND METHOD: The present
      study analyzed the data of inpatients and outpatients with a diagnosis of
      thalssemia according to ICD10 coded D56, D56.0, D56.1, D56.2, D56.3, D56.4, D56.8
      and D56.9 which came from nationwide health financing schemes in the fiscal year
      2010. RESULTS: The overall admission rate and OPD visit rate were 154 and 562 per
      100,000 populations and higher in children and adolescents. The overall mortality
      rate was 1.13 per 100,000 populations. The total healthcare cost was 744,998,997
      Baht or US$ 23,486,727 per year. Blood transfusion rate was significantly higher
      among children and adolescents. The thalassemia-related complications commonly
      occurred at the second and the third decades of life. CONCLUSION: The admission
      rate, OPD visit rate, blood transfusion rate were higher among children and
      adolescents. The total healthcare cost was high which was nearly 745 million Baht
      per year. The hospital cost, length of stay and major complications were
      increased with age.

PMID- 23130458
TI  - Disease burden of immune thrombocytopenic purpura among adult patients: the
      analysis of Thailand healthcare databases 2010.
AB  - BACKGROUND: Immune thrombocytopenic purpura (ITP) is not rare disease and it
      ispotentially fatal, particularly in patients with bleeding events which usually
      lead to hospitalization. Current data on the impact and disease burden of ITP in
      Thailand are lacking. OBJECTIVE: To determine admission rate, mortality rate,
      hospital cost, length of hospital stay, co-morbidities, treatment and major
      bleeding events in patients with ITP. MATERIAL AND METHOD: The authors analyzed
      the data of inpatients with a diagnosis of ITP according to ICD10 coded D69.3
      which were retrieved from a nationwide health financing schemes in fiscal 2010.
      The data were analyzed by age groups, gender and health financing schemes.
      RESULTS: The overall admission rate and mortality rate were 7.68 and 0.29 per
      100,000 populations, respectively and increased with age. Women were predominant.
      Average hospital costs and hospital stays were 27,133 Baht and 6.7 days per
      admission, respectively and slightly higher among men than women. The most common
      co-morbidity was hypertension. Gastrointestinal hemorrhage was the most common
      bleeding event which was 21.5 per 1,000 admissions. Patients in the civil servant
      medical benefit scheme had the highest percentage of high cost treatment
      accessibility. CONCLUSION: The admission rate, mortality rate and major bleeding
      events increased with age and was higher among women than men. Average hospital
      cost and length of hospital stay are higher in men than women. Common co
      morbidities may be related to the treatment of ITP There are the differences in
      high-cost treatment accessibility between health insurance schemes.

PMID- 23130459
TI  - Delirium in hospitalized elderly patients of Thailand; is the figure
      underrecognized?
AB  - BACKGROUND: Delirium is a frequent complication associated with hospitalization
      of older adults leading to serious complications but it is potentially
      preventable. The overall data regarding admission rates and its impact in Thai
      geriatrics are limited. OBJECTIVE: To identify admission, mortality rates of
      older persons with delirium and its consequences. MATERIAL AND METHOD:
      Information on illness of inpatients and casualties came from hospitals
      nationwide and from hospital withdrawals from the three health insurance schemes
      in fiscal 2010. The data included 96% of the population. The data were analyzed
      by age groups in delirious patients. RESULTS: Delirium occurred in 11,410 of all
      admissions; contributing admission and mortality rates of 155.4 and 6.4/100,000
      older persons. These figures increased with age. The average length of stay in
      persons with and without delirium were 22.3 and 5.4 days and the average hospital
      charges were 53,174 and 18,230.8 Baht, respectively. CONCLUSION: The admission
      rate of patients with delirium was lower than prior reports; underdetection and
      underreport should be considered. Admission and mortality rates rose with age.
      There was an increase in length of stay and hospital charges.

PMID- 23130460
TI  - Epidemiology of mental and behavioral disorders among the elderly: based on data
      of hospitalized patients in Thailand 2010.
AB  - BACKGROUND: To date, only small, selected groups of elderly hospitalized with
      mental and behavioral disorders (EHMBD) have been studied. Since no national
      epidemiological studies have been published, the recent advent of universal
      healthcare in Thailand makes doing such a study timely for improving the medical
      curricula and service provision. OBJECTIVE: To analyze the epidemiology of the
      EHMBD in the year 2010 of Thailand. MATERIAL AND METHOD: The data analyzed were
      gathered from Medical Expense Reimbursement forms submitted for the fiscal year
      2010. The particular focus of this research was on elderly inpatient aged 60
      years and over with ICD-10 (for 2010) diagnosis: F00-F99 Mental and Behavioral
      Disorders. The authors extracted and analyzed the number of in-patient department
      (IPD) admissions, psychiatric diagnoses, length of hospital stays, hospital
      charges and mortality rate. Data were analyzed using SPSS 17 for Windows.
      RESULTS: In 2010, EHMBD accounted for 11,418 admissions which was 1.56 admission
      per 1000 elderly people or 13.9% of overall admission (19 years and over). Of the
      11,418 admission, 44 died (0.39%). The mean in-patient charges/admission in Thai
      Baht (SD) for the EHMBD with any F00-F99 diagnosis was 12,896 (51,659). The
      average range of stay was 8.3 +/- 22.2 days. The leading diagnosed clusters of
      behavioral and mental disorders were organic mental disorders (F00-F09: 23.8%),
      neurotic, stress-related and somatoform disorders (F40-F48: 21.1%); and mental
      and behavioral disorders due to use of alcohol (F10: 20.3%). Alcohol use
      disorders among the elderly resulted in four times more men being hospitalized
      than women. Regarding the F30-F39 cluster mood (affective) disorders, the
      prevalence of depressive episodes increased with age and bipolar affective
      disorder decreased with age. CONCLUSION: The prevalence of hospitalization among
      the elderly with mental and behavioral disorders was about one-eighth that of all
      admission of adult from 19 years old. Death was an uncommon result. The most
      common psychiatric diagnoses were organic mental disorders, neurotic, stress
      related and somatoform disorders and mental and behavioral disorders due to use
      of alcohol.

PMID- 23130461
TI  - Geriatric hospitalizations due to fall-related injuries.
AB  - BACKGROUND: Fall is a preventable condition associated with disability and
      mortality in elders. The overall data regarding admission rates and its impact in
      Thai elderly are lacking. OBJECTIVE: To identify admission, mortality rates of
      older persons with fall, its causes and consequences. MATERIAL AND METHOD:
      Information on illness of inpatients and casualties came from hospitals
      nationwide and from hospital withdrawals from the 3 health insurance schemes in
      fiscal 2010. The data included 96% of the population. The data were analyzed by
      age groups in older patients with fall. RESULTS: There were 311,132 falls of all
      admissions; accounting for admission and mortality rates of 423.4 and
      11.1/100,000 older persons. The number rose with age. Slipping, tripping were the
      major causes. The average length of stay (LOS) of fallers with and without
      fractures was 8.1 and 6.4 days. The average hospital costs in these same groups
      were 25,728 and 19,419.3 Baht. CONCLUSION: The increasing age is related to an
      increased admission and mortality rates of fall. Slipping, tripping was the
      frequent causes. Greater LOS and hospital charges were found in fallers with
      fractures. Allied-healthcare workers should routinely implement a fall assessment
      and educate modifiable factors to elders to prevent future fall.

PMID- 23130462
TI  - Health insurance system and healthcare provision: nationwide hospital admission
      data 2010.
AB  - BACKGROUND: The three major health insurance systems are different in their
      medical service coverage, reimbursement process and choice of providers; leading
      to the question of how great are the variations in the healthcare offered and
      disease outcomes. OBJECTIVE: To assess whether differences exist and to analyze
      the effects of on healthcare provision and disease outcomes in the adult
      population across the three health insurance systems. MATERIAL AND METHOD: The
      authors analyzed the disease outcomes of the 23 major ICD-10 disease groups among
      the three major health insurance systems to obtain the death rates, levels of
      healthcare provision and the hospital charges. Factors influencing mortality
      rates were evaluated by multiple logistic regression analysis. RESULTS: The
      community, general, tertiary care and private hospitals provided hospitalization
      for 41.4%, 22%, 27.3% and 9.3% of hospitalized adult patients, respectively.
      Infectious & parasitic diseases were the most common causes of admissions.
      Disease of the digestive system was the most common cause of admission in general
      hospitals while malignancy was the most common in the tertiary care hospitals.
      Patients with congenital malformation, neoplasm, mental and behavioral disorder
      and diseases of the eye were commonly treated at tertiary care hospitals. The
      mean and median of hospital charges were highest in the Civil Servant Medical
      Benefit System (CSMBS) (26,668; 10,209 Baht), followed by the Social Security
      System (SSS) (21,455; 9,713 Baht) and the Universal Coverage System (UC) (13,086;
      5,246 Baht). The respective overall mortality rates for the CSMBS, SSS and UC
      were 4.40%, 1.38% and 3.32%. After adjustment, however a significant association
      between UC and mortality was found with an odds ratio of 1.43 (1.40-1.45) as
      compared to CSMBS. In addition, other factors most influencing mortality rates
      were male sex, elderly age, and the levels of healthcare. CONCLUSION: The
      differences in charges for some groups of diseases and significantly different
      clinical outcomes across schemes existed. The differences in disease outcomes
      were not adjusted for socioeconomic status and disease severity, requiring a
      cautious interpretation; nevertheless, an association with a higher mortality
      rate under the UC scheme for inpatient services need prompt further study

PMID- 23130463
TI  - Comparative effectiveness of three national healthcare schemes in Thailand: in
      hospital medical expenses for diabetes and hypertension in 2010.
AB  - OBJECTIVE: To compare the health insurance schemes regarding treatment of
      diabetes (DM) and hypertension (HT). MATERIAL AND METHOD: In-patient expense data
      for all ICD-10 DM and HT for 2010 were accessed from the National Health Security
      Office (UC), the Social Security office (SS) and the Civil Servants Benefit
      System (CSMBS). Mean hospital stay charges and mortality rates were calculated
      and compared across schemes and types of hospital. RESULTS: Thais > or = 19 years
      accounted for 4,863,939 admissions (12.6% DM-All; 17.9% HT-All). Average
      admission per case was higher for DM-All (1.66) than HT-All (1.46). CSMBS
      patients trended to be older than UC and SS. Most under UC were admitted to
      primary care (51.9% DM-All; 50.0% HT-All) vs. tertiary under CSMBS (45.5% DM-All;
      48.4% HT-All). Median of stay under CSMBS was longer (1.3-2.0x) and charges
      higher (1.3-1.6x) than UC for all levels for both DM and HT Mortality rate under
      CSMBS was higher than UC in primary care for both DM and HT while respective
      rates were higher under UC than CSMBS for secondary (DM-All: 9.9 vs. 8.1; HT-All:
      8.2 vs. 6.6) and tertiary care (DM-All:11.7 vs.8.6; HT-All: 9.8 vs. 6.8).
      CONCLUSION: Inequalities among three health insurance schemes for DM and HT
      including hospital charge, hospital stay and mortality rate according to health
      care settings for DM and HT were shown, effectiveness improvement is needed.

PMID- 23130464
TI  - Evaluation of causes-of-death: which statistics should we rely on, hospital
      deaths or vital statistics?
AB  - BACKGROUND: Age-specific causes of death yield important information for planning
      health services and medical education. OBJECTIVE: To compare the age-specific
      causes of death between in-hospital deaths and death registration statistics.
      MATERIAL AND METHOD: Information on in-hospital mortality in fiscal 2010 was
      extracted from the three health insurance schemes. Death registrations (ICD-10
      coding) were from the Bureau of Registration Administration, Ministry of Interior
      Statistics on the age-specific causes of death were analyzed. RESULTS: In
      hospital deaths numbered 132,512 (47.5% occurring in tertiary care) vs. 411,331
      recorded in vital statistics (68% died outside hospitals). Most (74%) infants
      died in-hospital so causes were clearly documented vs. death registration. A
      minority (6.2%) of in-hospital deaths and of death registrations (9.7%) were due
      to unnatural causes. The majority (79.5%) of unnatural deaths died before
      arriving at hospital. Ill-defined codes for causes of death were found in 6.1% of
      in-hospital records and 42.2% of death registrations. After censoring ill-defined
      codes, the ten leading, age-specific causes of death agreed between the two data
      sets. CONCLUSION: Medical personnel should receive training to do proper death
      certification. Periodic validation of hospital COD certification should also be
      done. Use of verbal autopsy in the Thai context would help to standardize record
      keeping and to reduce ill-defined codes for deaths occurred outside hospital.

PMID- 23130465
TI  - Road traffic injuries in Thailand: current situation.
AB  - BACKGROUND: Road traffic injuries are a major public health problem in Thailand.
      The number of mortalities, morbidities and disabilities are huge, greatly
      affecting the individual victims, the families, society and the nation as a
      whole. OBJECTIVE: To study the current situation regarding traffic injuries in
      Thailand. MATERIAL AND METHOD: Retrospective study from multiple national data
      sources RESULTS: For over ten years, the annual death toll due to road accidents
      has been more than ten thousand Thais. The situation remains critical with a
      higher mortality and morbidity than many other low or middle income countries.
      Two-thirds of the victims were males: 80% were under 40 years of age. Most (80%)
      of the injured and dead were motorcyclists. The large number of traffic crashes,
      injuries, disabilities and deaths resulted in more than 168 thousand million Baht
      in economic losses in 2002. These losses are trending to increase. CONCLUSION:
      Traffic injuries are a persistent major public health concern primarily because
      of a lack of adherence to the use of safety restraints and obedience of traffic
      laws. The nation must not hesitate to increase efforts to address these problems,
      as they are costing life and limb of Thais every hour of every day, as well as
      adding a huge economic burden.

PMID- 23130466
TI  - From health situation to health education and health service reforms for Thai
      society.
AB  - BACKGROUND: Health problems and service utilization patterns among Thai
      populations have changed significantly over the past three decades. It is
      imperative to scrutinize the changes so that the health service and human
      resource development systems can appropriately respond to the changing health
      needs. OBJECTIVE: To synthesize critical issues for future planning of health
      service reforms, medical education reforms and health research for Thai society.
      MATERIAL AND METHOD: The authors analyzed data on health service utilization,
      types of illnesses and hospital deaths among Thais in the fiscal year 2010.
      Information on the illnesses of in-/out-patients and hospital deaths was
      extracted from the three main health insurance schemes providing coverage to 96%
      of the population. The authors then synthesized the key issues for reforming
      medical education and health services. RESULTS: In summary, Thai patients have
      better access to health services. The total number of out-patient visits was
      326,230,155 times or 5.23 visits per population. The total number of in-patient
      admissions was 6,880,815 times or 0.11 admissions per population. The most
      frequent users were between 40-59 years of age. The most common conditions seen
      at OPD and IPD and the causes of in-hospital mortality varied between age-groups.
      The key health issues identified were: psychosocial conditions, health behaviour
      problems, perinatal complications, congenital malformations, teenage pregnancy,
      injury, infectious diseases, cardiovascular diseases and neoplasms. Medical
      education reforms need to be designed in terms of both undergraduate and post
      graduate education and/or specialty clinical needs. Health service reforms should
      be designed in terms of patient care systems, roles of multidisciplinary teams
      and community involvement. CONCLUSION: The government and other responsible
      organizations need to actively respond by designing the health service systems
      and human resource development systems that are relevant, appropriate and
      integrated. Different levels of care need to work collaboratively in order to
      achieve the greatest quality and efficiency.

PMID- 23130467
TI  - Adverse drug reactions and outcome of short course anti-tuberculosis drugs
      between single daily dose and split drug dose (BID) in pulmonary tuberculosis.
AB  - BACKGROUND: Standard six months short course regimen for treatment of pulmonary
      tuberculosis is very effective and is recommended as standard treatment. But this
      regimen composes of many drugs and causes high adverse drug reactions especially
      gastrointestinal irritation. Spitted administration of drugs to two times a day
      may reduce adverse drug reactions. OBJECTIVE: To study adverse drug reactions and
      outcome of single daily versus split drug (two times a day) administration of
      standard six month short course regimen in newly diagnosed pulmonary
      tuberculosis. MATERIAL AND METHOD: Newly diagnosed pulmonary tuberculosis
      patients of the Central Chest Institute of Thailand were randomized to receive
      standard six months regimen once daily or two times a day (split drug). Patients
      were followed-up every two weeks and a questionnaire was used to detect adverse
      drug reactions. Outcome of treatment was evaluated according to national
      tuberculosis treatment guideline. RESULTS: 122 pulmonary tuberculosis were
      eligible for the present study and 61 patients were enrolled to each group of
      once daily or split drug regimen. Pulmonary tuberculosis patients who received
      split drug regimen had a higher cure rate but not statistical significance
      because of lower transfer out rate. Adverse drug reactions were similar in both
      groups of patients who received once daily and split drug regimen. Although split
      drug group had lower gastrointestinal adverse drug reactions. CONCLUSION: Split
      drug regimen has the same cure rate of treatment as single daily regimen and same
      adverse drug reactions.

PMID- 23130468
TI  - Benefit of serum-effusion albumin gradient in congestive heart failure patients.
AB  - OBJECTIVE: To compare between light's criteria and serum-effusion (S-E) albumin
      gradient in diagnosis of transudate effusion in congestive heart failure (CHF)
      patients. MATERIAL AND METHOD: Eighty-six patients who had pleural effusion and
      suspected CHF were enrolled in the present study between October 2008- September
      2010. Suspected CHF was defined by clinical or echocardiography. Inform consents
      were given by all volunteers. Exclusion criteria was previous thoracotomy or
      coronary bypass graft 3 months before present study. Thoracocentesis was done to
      evaluate transudate effusion by light's criteria and S-E albumin gradient > 1.2
      mg/dl. RESULTS: 12 (13.95%), 56 (65.11%), 17 (19.76%) of all were pure pleural
      disease, pure CHF, combination of pleural disease and CHF.
      Sensitivity/specificity/accuracy of S-E albumin gradients and light's criteria in
      diagnosis of CHF (both pure and combined) were 90.1/33.3/80.2%, 64.7/80.0/67.4%.
      No correlation between amount of diuretic drug and "exudate" criteria from
      lights' (p = 0. 66). 25 (27.2%) patients were previous post thoracotomy or
      coronary bypass graft. 7 of 25 patients had loculated effusion. There was
      correlation between previous surgery with loculated effusion and effusion from
      combination of pleural disease and CHF (p = 0.22). CONCLUSION: There is benefit
      to use S-E albumin gradient > 1.2 mg/dl to diagnosis patients who were suspected
      CHF with or without pleural disease. The authors recommended to use S-E albumin
      gradients combined with Light's criteria in suspected CHF patients.

PMID- 23130470
TI  - Accuracy of endobronchial ultrasound guided-transbronchial needle aspiration in
      mediastinal lymph node diagnosis.
AB  - OBJECTIVE: To evaluate the efficacy of Endobronchial ultrasound guided
      transbronchial needle aspiration (EBUS-TBNA) for biopsy specimens with adequate
      evaluable lymphocytes and mediastinal lymph node diagnosis. MATERIAL AND METHOD:
      Prospective cohort study. Over 18 year old patients with mediastinal or hilar
      lymphadenopathy, with short axis diameter greater than 10 mm on chest CT were
      indicated to undergo EBUS-TBNA. When a node was detected, an aspiration was
      performed under ultrasound guided. The primary end point was the percentage of
      biopsy specimen with adequate evaluable lymphocytes that had been evaluated by
      cytopathologist. Secondary endpoint was the percentage of EBUS-TBNA diagnosis
      result. RESULTS: 82 patients with mediastinal or hilar lymphadenopathy underwent
      EBUS-TBNA. Average size of lymph node was 1.57 x 1.49 cm. The overall of the
      diagnostic accuracy was a percentage of biopsy specimen with adequate evaluable
      lymphocytes as 97.7%. For mediastinal lymph node diagnosis, the cytological
      evaluation demonstrated that the positive for malignancy, atypical or suspicious
      for malignancy, negative for malignancy and non-diagnosis were 37.2%, 9.3%, 2.3%
      and 51.2%, respectively. In case of positive for malignancy, non-small cell
      carcinoma, adenocarcinoma, bronchoalveolar cell carcinoma and small cell
      carcinoma were found 62.5%, 15.6%, 3.1% and 18.8%, respectively. Additionally,
      the pathological examination showed that positive for malignancy, atypical or
      suspicious for malignancy, negative for malignancy and non-diagnosis were found
      35.4%, 7.3%, 3.6% and 53.7%, respectively. There were no complications during all
      of the procedures. CONCLUSION: High percentage of biopsy specimen with adequate
      evaluable lymphocytes can be obtained in EBUS-TBNA. This finding suggested that
      this method should be considered for mediastinal lymph node diagnosis.

PMID- 23130469
TI  - Bacteria associated with acute exacerbations of chronic obstructive pulmonary
      disease requiring mechanical ventilation and antimicrobial management in
      Respiratory Care Unit of Central Chest Institute of Thailand.
AB  - OBJECTIVE: To investigate the role of bacterial infection, antimicrobial
      sensitivity and antibiotics usage in severe acute exacerbations of COPD requiring
      mechanical ventilation in the respiratory care unit of the central chest
      institute of Thailand. MATERIAL AND METHOD: All data were analyzed from medical
      records of 38 patients admitted in RCU of CCIT during 1 November 2008-31 August
      2011 with severe acute exacerbations of COPD requiring mechanical ventilation.
      The tracheobronchial aspirates specimens were collected for Gram stain,
      quantitative culture and sensitivities testing. The sera were tested for
      antibodies to Chlamydophila pneumoniae and Mycoplasma pneumoniae with the
      immunofluorescence test. RESULTS: Bacterial pathogens were isolated by
      quantitative culture from 18 of 38 patients (47.3%). Gram-negative bacilli were
      the predominant organisms. K. pneumoniae was the predominant isolates 7 cases
      (18.4%) followed by H. influenzae 3 cases and P. aeruginosa 3 cases (7.9% each).
      A single pathogen was isolated from 12 patients (31.6%), two pathogens were
      isolated from 5 patients (13.2%) and three pathogens from 1 patient (2.6%).
      Serological samples were positive for Chlamydophila pneumoniae in 5 (13.2%)
      cases. 1 of these patients had coinfection with Acinetobacter baumannii. In the
      RCU, 33 (86.8%) patients were empirically treated with antibiotic. Ceftriaxone
      was the most commonly used antibiotic. CONCLUSION: 57.8% (22/38 cases) of the
      patients with severe exacerbations in COPD requiring mechanical ventilation
      caused by bacterial infection, Gram-negative bacilli were the predominant
      organism with a resistance to commonly used antibiotics of K. pneumoniae, P.
      aeruginosa, S. aureus, E. coli, A. baumannii, P. mirabilis, S. dysgalactiae and
      S. pneumoniae. 13.2% of the patients had serological evidence of Chlamydophila
      pneumoniae infection.

PMID- 23130472
TI  - Efficacy of computed tomography-guided fine needle aspiration in diagnosis of
      lung mass by trained internists.
AB  - OBJECTIVE: To determine the efficacy of Computed Tomography (CT)-guided fine
      needle Aspiration (FNA) in diagnosis of lung masses by trained internists
      including factors affecting the adequacy of specimens and occurrence rate of
      complications. MATERIAL AND METHOD: 96 patients, aged 25-86 years old underwent
      CT-guided FNA of thoracic lesions by internists who had been trained for this
      procedure at the Central Chest Institute of Thailand during March 2007-2008.
      Demographic data, procedure success and adequacy of specimens for cytological
      evaluation were summarized including other factors-size and depth of lesion,
      condition of emphysema and complications of procedure. RESULTS: Success of
      procedure was 97.9%. Adequacy of specimen was 94.7%. Occurrence of pneumothorax
      was 19 out of 96 cases (19.8%). And 1 case needed to insert inter costal drainage
      (1.1%). Hemoptysis after procedure was 1.06%. Besides, larger than 3 cm in
      diameter of lesion presented satisfied specimens more than that of the smaller
      one. Pneumothorax is the most common complication, which revealed a statistically
      significant with emphysema around mass. CONCLUSION: FNA is an effective and
      useful tool in diagnosis of pulmonary lesions for trained internists. Success of
      procedure and adequacy of specimen for cytological evaluation are considerably
      high and low complications occurred.

PMID- 23130471
TI  - Clinical outcomes of multidisciplinary care in chronic obstructive pulmonary
      disease patients at the Central Chest Institute of Thailand.
AB  - OBJECTIVE: To compare clinical outcomes before and after are enrolled study
      within 1 year and factors related to Chronic Obstructive Pulmonary Disease (COPD)
      exacerbations after enrolled. MATERIAL AND METHOD: COPD patients who were
      compatible with inclusion criteria in COPD clinic at the Central Chest Institute
      of Thailand between March 2007 and July 2010. Baseline characteristics, COPD
      management program, bronchodilator used, and clinical outcomes were recorded by a
      search of retrospective databases, as well as the patient medical records.
      RESULTS: A total of 247 enrolled patients compatible with inclusion criteria were
      analyzed. Most of the patients were male, 240 patients (97.2%). The average age
      of the patients was 69.3 +/- 9.1 years. The majority of patients were in GOLD
      stage II, 121 patients (49.0%). After multidisciplinary care was performed. In an
      overall 219 patients (88.6%) of COPD patients received appropriate bronchodilator
      treatment classified by GOLD stage which had different proportions in each stage
      significantly [stage I = 45 patients (100%), stage II = 103 patients (86.6%),
      stage III = 58 patients (86.6%), stage IV = 13 patients (92.8%),p = 0.026]. COPD
      exacerbations frequency (0.9 +/- 1.6 vs. 0.3 +/- 0.9, p<0.001), COPD related
      hospitalizations (0.2 +/- 0.8 vs. 0.1 +/- 0.4, p < 0.001), COPD related
      respiratory failure (0.04 +/- 0.25 vs. 0.008 +/- 0.090, p = 0.020) were
      significantly decreased after enrolled. On multivariate analysis, COPD patients
      who had exacerbations frequency more than one time per year were prone to have
      repeated COPD exacerbations approximately three times more than other COPD
      patients (Adjusted Odds ratio 2.80, 95% CI, 1.08 to 7.26, p = 0.034). CONCLUSION:
      Multidisciplinary care in COPD patients can significantly improve clinical
      outcomes.

PMID- 23130473
TI  - Left ventricular function after permanent pacemaker in pacemaker clinic follow
      up.
AB  - BACKGROUND: Chronic right ventricular pacing has deleterious effects to left
      ventricular function which may be asymptomatic. Prevalence of LV dysfunction
      (LVEF < 50%) in RV pacing in Thai patients is not known. MATERIAL AND METHOD:
      Patients in the Central Chest Institute of Thailand (CCIT) pacemaker clinic were
      retrospectively reviewed for their demographic and pacemaker data together with
      echocardiographic data for LV function. Analysis was done for those who were
      implanted for more than one year period. RESULTS: Among the studied 118patients,
      male = 51 and female = 67, mean follow-up time 6.43 +/- 5.66 years, LV systolic
      dysfunction was identified in 21 (17.80%). Compared to those with no LV
      dysfunction, echocardiographic parameters showed larger LVsize (EDD 49.86 +/-
      8.95 vs. 43.81 +/- 5.56 mm) and less thickness of the LV wall (11.05 +/- 1.60 vs.
      12.49 +/- 2.79 mm). Studied clinical and pace parameters for correlation were
      hypertension (p = 0.048), coronary artery disease (p = 0.008), percent of
      ventricular pacing (p = 0.06), duration after implantation (p = 0.23), mode of
      pacing (p = 0.275), indication of implantation (p = 0.32, site of pacing lead (p
      = 0.279), moderate to severe MR (p = 0.003) and moderate to severe TR (p = 0.04).
      CONCLUSION: LV dysfunction after pacemaker implantation was not infrequent.
      Parameters correlated to it were previous LV dysfunction, hypertension, coronary
      artery disease and increased amount of ventricular pacing. Mode of pacing and
      site of pacing lead were not correlated.

PMID- 23130474
TI  - Impact of right ventricular pacing on right ventricular function.
AB  - BACKGROUND: The benefits of right ventricular pacing in patients with symptomatic
      bradycardia are well recognized. Currently, left ventricular (LV) function after
      cardiac pacing has already been extensively investigated. However existing data
      on right ventricular (RV) function in these patients is extremely limited.
      MATERIAL AND METHOD: To test this, records of RV and tricuspid valve function of
      patients with a pacemaker measured at least a year after implantation were
      reviewed for a prevalence of RV dysfunction. The patients were also divided into
      those with and without RV dysfunction. Factors affecting the two groups were
      evaluated. RESULTS: RV dysfunction and moderate to severe tricuspid valve
      regurgitation were found in approximately 4% and 21% respectively in cardiac
      pacing patients with mean implantation duration of 6.4 years. Compared to normal
      RV function, factors presumed to affect on RV dysfunction including site of
      pacing, pacing mode and percentage of ventricular pacing were not significantly
      different (p = 0.54, 0.37 and 0.12 respectively). CONCLUSION: Based on these
      data, the prevalence of right ventricular dysfunction appears to be infrequent
      and factors that were assumed as contributors to LV dysfunction failed to show
      significant contributions to RV dysfunction.

PMID- 23130475
TI  - Rheumatic mitral valve repair: experience of 221 cases from Central Chest
      Institute of Thailand.
AB  - Rheumatic heart disease is a major problem in Thailand and this region. Surgical
      management is still a dilemma and problematic. Current understanding of mitral
      valve complex and its dynamics in combination with improvement of surgical
      techniques allow surgeon to repair rheumatic mitral valve disease better. Several
      innovative approaches have been introduced recently and greatly enhances the
      success of mitral valve repair in this clinical entity. This case report reviews
      the authors' current approaches and results in the repair of rheumatic mitral
      valve at Central Chest Institute of Thailand.

PMID- 23130476
TI  - Endoscopic conduit harvesting and conventional conduit harvesting for coronary
      artery bypass graft surgery.
AB  - Conventional conduit harvesting used for coronary artery bypass graft for many
      decades but there has been some wound complication problem. Endoscopic conduit
      harvesting is a minimal invasive surgery for reduced wounds complication. The
      authors aimed to compare the result between two techniques. MATERIAL AND METHOD:
      Prospective enroll of 100 patients for elective coronary artery bypass graft
      surgery. Divided in 2 groups. The first groups was a convention conduit
      harvesting (C groups) and the second groups was endoscopic conduit harvesting (E
      groups). The endoscopic conduit harvesting performed using the Maquet Vasoview
      system under CO2 inflation assisted. RESULTS: Endoscopic conduit harvesting was
      successful 94%. Harvest time C group 32.4 mins E group 48.9 mins, ET CO2 C group
      40.3, E group 50.9, Wounds infection C group 6% E group O, wounds echymosis C
      group 6% E group 44%. CONCLUSION: Endoscopic conduit harvesting showed better
      results with conventional conduit harvesting in wounds with serious complications
      but they need more harvest time and risk of CO2 embolism. However a long term
      graft patency needs more investigation.

PMID- 23130477
TI  - Patient-prosthesis mismatch has no influence on in-hospital mortality after
      aortic valve replacement.
AB  - OBJECTIVE: To analyze the relationship between prosthetic aortic valve orifice
      and body surface area (Effective Orifice Area Index, EOAI) and in-hospital
      mortality after aortic valve replacement. MATERIAL AND METHOD: A prospective
      study was conducted between October 2007 to September 2010, 536 patients
      underwent isolated aortic valve replacement (AVR) was recorded on preoperative,
      operative and postoperative data. Patient Prosthesis Mismatch (PPM) was
      classified by Effective Orifice Area Indexed (EOAI) by prosthetic valve area
      divided by body surface area as mild or no significance if the EOAI is greater
      than 0.85 cm2/m2, moderate if between 0.65 cm2/m2 and 0.85 cm2/m2, and severe if
      less than 0.65 cm2/m2. Statistical differences were analyzed by Chi-square and
      student t-test with p-value less than 0.05 considered significant. RESULTS: There
      were 304 men, mean age was 60.98 years, mean valve orifice area 1.69 cm2, body
      surface area 1.60 m2, cross clamp time 1.13 hrs., bypass time 1.67 hrs.
      Mechanical valves were used in 274 patients (51.2%) and Bioprosthesis were used
      in 181 patients (48.8%). PPM was found in 33.7%, 6.7% was severe PPM, 27% was
      moderate PPM and 66.3% has no significant PPM Over all in-hospital mortality was
      1.5%. There was no significant difference in hospital mortality between no PPM
      group, moderate PPM and severe PPM group (1.4% vs. 1.4% vs. 5.4%, p-value =
      0.86). CONCLUSION: In a large aortic valve surgery population, moderate and
      severe patient prosthesis mismatch occurred in 35.6% of patients but had no
      influence on in-hospital mortality.

PMID- 23130478
TI  - Asbestos-related diseases in Thailand and review literature.
AB  - Asbestos is a harmful substance that can cause both malignancy and non-malignancy
      in humans. Although it has been used in Thailand for several years, few cases of
      asbestos-related diseases were reported. Concerning about high consumption and
      long exposure of asbestos in the country, the incurable but preventable diseases
      caused by asbestos will be the health problem in the near future. The authors
      presented 2 cases with asbestos-related diseases, one diagnosed as malignant
      mesothelioma and the other as asbestosis.

PMID- 23130479
TI  - Percutaneous coronary intervention in patients with anomalous origin of coronary
      artery.
AB  - Percutaneous coronary intervention in patients with anomalous origin of right
      coronary artery from left sinus of Valsalva was performed in Central Chest
      Institute during 2005-2009. The diagnosis of this type of congenital anomaly is
      always difficult, since it requires high operator's consideration and experience.
      Standard catheter curve desired for general coronary angiography is also not
      suitable for the abnormal origin of artery, especially when coronary intervention
      is to be performed. The authors report a series of these anomalous coronary
      patients with atherosclerotic disease who underwent transcatheter coronary
      intervention using Extra Backup left coronary guiding catheters, which help
      cannulation of the anomalous ostium and enhance the operation success.

PMID- 23130480
TI  - Cases report: Experience with rheolytic thrombectomy device (Angiojet) in acute
      ST elevation myocardial infarction with large amount of coronary thrombus.
AB  - BACKGROUND: Primary percutaneous coronary intervention (PCI) in acute ST
      elevation myocardial infarction (STEMI) is a clinical challenge. Adequate
      thrombus removal before stenting is an important factor that predicts procedural
      success, and finally reflects to clinical outcomes. CASES REPORT: In the present
      report, 2 cases of acute STEMI underwent primary PCI. Coronary angiogram (CAG) in
      both cases showed a large amount of coronary thrombus (TIMI thrombus grade 4 &
      grade 5), with no response to several attempts of manual aspiration with thrombus
      aspiration catheter Then, Angiojet rheolytic thrombectomy, a catheter-based,
      device was used antegradely. Repeated CA G showed thrombus was significantly
      eliminated. Both patients were successfully stented with direct stent technique
      at culprit arteries, resulted in good angiographic results and inhospital
      outcomes. CONCLUSION: Angiojet, a rheolytic thrombectomy device, is a viable
      option to remove thrombus in primary PCI, especially in cases with massive
      thrombus load and failed manual aspiration.

PMID- 23130481
TI  - Giant coronary artery aneurysm mimicking a mediastinal mass: a case report and
      review.
AB  - Giant coronary artery aneurysm is a rare disorder which remains asymptomatic in
      most patients. However it appears that serious complications may develop at some
      point of time and will likely require surgical intervention. A patient with a
      huge coronary aneurysm ten centimeters in diameter successfully treated with
      surgical intervention was presented.

PMID- 23130482
TI  - The physical health and self-esteem of the grandmother raising grandchildren in
      rural areas of Thailand.
AB  - OBJECTIVE: To study the physical health and self-esteem, including factors that
      influence the self-esteem of grandmothers raising grandchildren in the rural
      areas of Northern Thailand. MATERIAL AND METHOD: A cross-sectional survey
      research was conducted among 400 grandmothers, aged 50-79 years, who raised their
      grandchildren in the rural areas of Northern Thailand. Participants were selected
      by cluster sampling. Data were collected through a structured interview from
      April to July, 2009 and analyzed by frequency, percentage, Pearson's product
      moment correlation coefficient and multiple regression analysis. RESULTS: 73.8%
      of grandmothers in the survey currently had health problems, 56.2% had a chronic
      disease of which hypertension was the most common and yet 44.5% displayed high
      self-esteem. The factors identified as influencing self-esteem were family
      relationships, age and social support. These factors provided 35.4% in predicting
      the self-esteem of grandmother who raised grandchildren with family relationship
      had the highest predictive value. CONCLUSION: The present study suggested the
      responsible organizations should organize the program to strengthen the family
      relationship and social support activity for the grandmother that will lead to
      the better health and heightening self-esteem.

PMID- 23130483
TI  - Factors influencing the mental health of the elderly in Songkhla, Thailand.
AB  - OBJECTIVE: To study the factors which influence the mental health of the elderly
      in Songkhla, Thailand. MATERIAL AND METHOD: A cross-sectional survey research was
      conducted among 250 elderly residents aged 60-94 years, using multi-stage random
      sampling. The data were collected through interview questionnaires circulated
      between February 22nd and March 22nd, 2011 and thereafter analyzed by frequency,
      percentage and multiple logistic regression. RESULTS: Most of the subjects
      (79.2%) had good mental health and 20.8% had poor mental health. The factors
      influencing their mental health were age, physical health status, presence of
      chronic disease, family relationship and membership or active participation in a
      civic or social group. Those aged 60-79 years reported 2.9 times better mental
      health than those who were 80-94 years. Those reporting good physical health
      status also reported having 6.5 times better mental health than those with poor
      physical health. Subjects without chronic disease reported 3.5 times better
      mental health than those reporting the presence of chronic diseases. Seniors with
      a good family relationship had 4.9 times better mental health than those who did
      not report a good family relationship and the subjects who were members of a
      social or civic group had 2.4 times better mental health than those who were not.
      CONCLUSION: The factors influencing mental health of the elderly were age,
      physical health status, chronic disease, family relationships and membership or
      participation in a civic or social group. To promote mental health amongst these
      people, responsible organizations should establish activities that promote good
      family relationships and encourage active participation in civic or social groups
      and support organizations.

PMID- 23130484
TI  - Health status and health promoting behaviors among aging workers in Thailand.
AB  - OBJECTIVE: To examine health status, health promoting behaviors and predictors of
      health promoting behaviors of Thai aging workers. MATERIAL AND METHOD: The
      subjects of this descriptive study were 2,312 aging workers (45-60 years) working
      in large, medium and small-sized industry in all regions of Thailand selected by
      multi-stage random sampling. Data was collected by using the self-administered
      questionnaire. RESULTS: About 59.3% of aging workers had perceived health status
      at good level, while 41.9% had underlying diseases and 15.4% had experienced work
      related accidents. Health promoting behaviors were mostly at fair and good level
      (49.8% and 47.6%, respectively). More than half of aging workers had health
      promoting behaviors related to self-actualization, exercise, and stress
      management at good level (63.6%, 58.7% and 53.1% respectively). Health
      responsibility, Nutrition and interpersonal relationship at fair level (51.2,
      49.6 and 51.5 respectively). Support from co-workers, attitude toward health
      promotion, health risk behaviors, support from media, accessibility to health
      promotion activities, support from family members, workplace health promotion
      policy, perceived health status and support from supervisors altogether could
      explain 25.1% of variance in health promoting behaviors of aging workers.
      CONCLUSION: To promote health promoting behaviors of aging workers, workplace
      should have health promotion policy in place,facilities and schedule of health
      promotion activities should also be arranged to encourage participation. In
      addition, co-workers and family members should be encouraged to motivate the
      involvement of aging workers in health promotion activities.

PMID- 23130485
TI  - Consequences and associated factors of youth gambling.
AB  - OBJECTIVE: To examine gambling behaviors, consequences and its associated factors
      among Thai youths. MATERIAL AND METHOD: A cross-sectional survey of 1,694
      students from Matthayom 1 (grade 7) to university undergraduate level was
      conducted using a self-administered questionnaire. Questionnaire items consisted
      of socio-economic characteristics, health behaviors, attitudes towards gambling
      and consequences of gambling. Factors associated with gambling experience were
      identified by multivariate logistic regression. RESULTS: Approximately 20% of
      youth gambling was reported. Gamblers had higher proportion of males, studying in
      vocational schools and lower GPA and history of smoking and alcohol consumption.
      Card games were the most common type of gambling, followed by football-betting.
      Approximately 10% of the gamblers potentially had pathological gambling. Factors
      positively associated with gambling included having friends (adjusted OR = 4.82)
      and relatives (adjusted OR = 2.48) who gambled. Having a GPA > or = 3.0 was
      negatively associated with gambling (adjusted OR = 0.58). The present study
      reported negative consequences of gambling including feeling of guilt, perception
      of poorer health and depression or insomnia after losing. CONCLUSION: Gambling
      prevention program should be developed and focused on student with poor study
      performance and wrecked relationships in family. Also, a surveillance system for
      health risk behaviors among youth in school and community should be established
      by the participation of multiple organizations.

PMID- 23130486
TI  - Self-care behaviours of chemotherapy patients.
AB  - OBJECTIVE: To present study self-care behaviours and variables associated with
      self-care behaviors of cancer patients treated with chemotherapy. MATERIAL AND
      METHOD: This is a descriptive, cross-sectional study in cancer patients receiving
      chemotherapy in out-patient department of the National Regional Cancer Center in
      Chonburi City. Interview questionnaire was the data collection instrument for 133
      purposive sampling. RESULTS: Survey result indicated that patients were highly
      aware of the support provided by staff on service supports, emotional supports
      and informational support. The present study results also found that the top 3
      patient self-care knowledge are, avoiding those who have cold when the patients
      have low white blood cells, eating hot (cooked well with heat) food and knowing
      the effects of chemotherapy on causing low red blood cells, lowplatelets and low
      white blood cells. The top 3 self-care behaviours of the patients were, always
      eat cooked food, inquire and understand the instructions from health personnel
      for self-care and always check herself/himself to maintain good health. However
      patients did not usually exercise at least 15 minutes every day, select the
      recreational activities adequately, and not finding ways to improve their own
      health. Results from hypothesis testing, indicated that only knowledge variable
      was associated with self-care behaviours of patients treated with chemotherapy.
      The demographic variables such as age, marital status, education level, income
      were not associated with self-care behaviours of patients treated with
      chemotherapy CONCLUSION: Knowledge is associated with self-care behaviours of
      cancer patients who received chemotherapy. Providing health promotion for
      patients is necessary for them to have better self-care behaviours.

PMID- 23130487
TI  - Core competencies to prevent and control chronic diseases of Tambol Health
      Centers' head in Thailand.
AB  - OBJECTIVE: To assess the core competencies to prevent and control chronic
      diseases of the head of Tambol Health Centers (THC) in Thailand. MATERIAL AND
      METHOD: This cross-sectional survey research was carried out with 2,049 heads of
      THC from the total population of 9,985. The samples were selected randomly from
      all provinces of every region. The data were collected through mail
      questionnaires and the reliability values of the three competency domains
      questionnaire were found to be between 0.75-0.93. Data analysis was done by
      computing frequency, percentage, arithmetic mean, Independent's t-test and One
      way ANOVA. RESULTS: The total core competency values of prevention and control of
      diabetes and hypertension of the THC heads were found at the high and moderate
      level (3.0% and 78.7%) respectively The similar finding was found in the
      competency domains in regard to "personal attribution", "intellectual capacity"
      while 8.0 percent and 46.2 percent of the respondents had the high and moderate
      level of "work skill" domain respectively. In addition, the differences of
      competency domains were found in accordance with the regions where the THC
      located, ability to develop a plan for disease prevention and readiness for
      changing behaviors of the risk groups. But the personal attributions with regard
      to gender age, family's economic status, and the location of the THC were not
      found to affect every competency domain. Except for the intellectual capacity
      domain found that the male THC heads had the higher level than the females and
      work skill domain of those THC heads working in the municipal areas had the
      higher level than those who worked outside the municipal areas. CONCLUSION: Core
      competencies of the heads of THC in chronic disease prevention and control were
      found at the "somewhat good" level except for the work skill domain which needed
      to be developed. Thus, the Ministry of Public Health should establish a specific
      policy and strategy on human resource development by using core competencies on
      chronic disease prevention and control as the core performance indicators.

PMID- 23130488
TI  - Effect of personal health record booklet (PHRB) to knowledge, self-efficacy and
      healthy behaviors among Thai population at risk of cardiovascular disease (CVD).
AB  - OBJECTIVE: To investigate an effect of a personal health record booklet (PHRB) to
      knowledge, self-efficacy and healthy behaviors among Thai population at risk of
      CVD. MATERIAL AND METHOD: The present study was a quasi-experimental study
      conducted in a primary care unit during November 2008 and January 2009. A random
      sample of 204 CVD risk population were recruited as a comparison group (n = 102),
      who received a regular follow-up and recorded routine blood pressure using
      booklet and an experimental group (n = 102), who received the regular follow-up
      and the intervention consisting of health education for CVD information and self
      monitoring practice. Data were collected by using self-administered
      questionnaires at the baseline, the 4th week and the 8th week. These data were
      analyzed by descriptive statistics, Chi-square test and GLM repeated measures.
      RESULTS: Knowledge score was significantly decreased although self-efficacy was
      increased over a time in the experimental group. However except the figure of
      sweet/cookies consumption, the mean score of healthy behaviors were not improved
      in the experimental group when compared to the comparison group. CONCLUSION: CVD
      information, activity illustrations with caption, health record section and daily
      self-monitoring tables in desired behaviors should be considered for inclusion in
      the booklet.

PMID- 23130489
TI  - Cancer risk perception and preventive behaviors among grilled meat vendors.
AB  - BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants
      that cause cancers in humans. Exposure results from incomplete burning of organic
      materials. Grilled meat vendors are occupationally exposed to PAHs in smoke from
      continuously burning charcoal and meat, which may have chance to get cancer.
      Individual risk perception is a critical antecedent of preventive behavior
      However relatively little is known about the cancer risk perception and
      preventive behaviors among grilled meat vendors. OBJECTIVE: The present study
      aimed to examine cancer risk perception and preventive behaviors and factors
      associated with preventive behaviors among grilled meat vendors in Bangkok,
      Thailand. MATERIAL AND METHOD: A cross-sectional survey was used in the present
      study. The subjects consisted of 40 males and 82 females grilled meat vendors who
      conducted their jobs at Victory Monument, Bang Lumpoo, Pratunam, Jakkawat or
      Patumwan. They were interviewed regarding cancer risk perception and preventive
      behaviors. Multiple logistic regression analysis was used to analyze data.
      RESULTS: Average cancer risk perception score was 23.3 +/- 3.3 out of 32. About
      79.5% of the subjects had high risk perception. The prevalence of good preventive
      behaviors was 86.1%. The three most frequent preventive behaviors among the
      subjects during grilling meat were using good quality charcoal (65.6%),
      ventilation fan (41.0%) and wearing long sleeves shirt (36.1%). Only 10.7% always
      used gloves. Multiple logistic regression analysis showed 2 factors were
      independently associated with preventive behaviors: educational level and risk
      perception. The subjects who had higher educational level or risk perception were
      more likely to develop better behaviors than those who had a lower educational
      level and perception (p < 0.05). CONCLUSION: In conclusion, the present study
      found that the educational background and cancer risk perception were associated
      with preventive behaviors among grilled meat vendors. To improve the preventive
      behaviors among grilled meat vendors, interventions focusing on cancer risk
      perceptions and considering educational background among target group are
      recommended.

PMID- 23130490
TI  - Policy measures on strengthening and developing capabilities for national tobacco
      control in Thailand.
AB  - OBJECTIVE: To assess the situation and report on a national capacity plan for
      tobacco control under the National Strategic Plan for Tobacco Control (NSPTC)
      2010-2014. MATERIAL AND METHOD: Systematic documentary review and analysis were
      managed by the working group. The results were discussed and provided
      recommendations by the sub-committee on developing the NSPTC 2010-2014. Seven
      meetings were organized from March 2009-January 2010. Eventually, the NSPCT 2010
      2014 was approved by the National Committee for Tobacco Control, chaired by the
      Minister of Public Health on 22 April 2010. RESULTS: The major result of the
      present study was brought to the National Capacity in Tobacco Control Plan under
      the NSPTC 2010-2014. The purpose of the plan is to strengthen and develop
      national tobacco control capacity before 2011. Seven strategic areas for National
      Tobacco Control Capacity have been proposed. They are, 1) tobacco control policy
      and leadership development, 2) developing an organizational structure and
      management systems, 3) developing surveillance, monitoring and evaluation
      systems, 4)formulate measures to support research and knowledge management, 5)
      capacity building and network expansion for tobacco control in various sectors,
      6) capacity building and expansion of a collaborative network for tobacco control
      at regional levels and 7) improving and strengthening tobacco control laws. In
      addition, the indicators, key players and support partners were addressed.
      CONCLUSION: Although the strength of the strategic plan on National Capacity in
      Tobacco Control is participatory planning process and result in the integrated
      and comprehensive capacity in tobacco control plan, but some concerns should be
      considers. They are infrastructure, evidence and networking and leadership.

PMID- 23130491
TI  - Cigarette consumption among foreign tourists in Thailand.
AB  - OBJECTIVE: To explore the cigarette consumption among foreign tourists in
      Thailand. MATERIAL AND METHOD: The data in this cross-sectional survey is
      collected by interviewing 655 foreign tourist smokers with questionnaires in
      congested areas including Suvarnabhum International Airport, Khao San Road,
      shopping centers and tourist attraction sites. The data was collected in October,
      2010, analyzed by descriptive statistic and the crude magnitude of cigarette
      consumption was calculated. RESULTS: The findings indicated that 62.9% of
      tourists were male and 58.9% were from European countries and 22.7% were from
      Asian countries. 59.2% smoked cigarettes sold in Thailand and were taxed legally.
      In that amount, 55.7% smoked imported cigarettes and only 3.5% smoked Thai
      cigarettes. 40.8% had brought cigarettes from their countries or bought
      cigarettes from Duty Free shops with the amount allowed by Thai law. The top 2
      popular brands were Marlboro and L&M. The main reason why they bought imported
      cigarettes in Thailand was that the price was cheaper or the same when compared
      with that in their countries. The cigarette consumption share crudely calculated
      was around 8.90 million packs. CONCLUSION: Foreign tourists smoked imported
      cigarettes distributed in Thailand and cigarettes brought from abroad. So, Free
      Trade Agreement in bilateral level or multilateral level need to be reviewed and
      should separate cigarettes from other goods. The tax barrier excise tax measure
      and permission law of carrying in 200 sticks should be reviewed in order to
      control cigarette consumption effectively.

PMID- 23130492
TI  - A multilevel study of smoking among youths in school at Buriram Province.
AB  - OBJECTIVE: The purpose of this cross-sectional study was to determine status of
      smoking among youths in school and to identify both student-level and school
      level factors on smoking. MATERIAL AND METHOD: A stratified two stage cluster
      sampling was employed to recruit 2,557 students in grades 10-12 and 30 teachers
      from 30 high schools in academic years 2010 in Buriram province, using a
      multilevel logistic analysis. RESULTS: The current smoking status was 9.0%
      overall, 19.0% and 1.3% for male and female respectively. The results from
      multilevel logistic analysis revealed that only 10.5% of variation in smoking was
      associated with difference in school characteristics. The following student-level
      factors entered into the multilevel logistic regression model according to their
      importance were self-efficacy-with the moderate and low self-efficacy having a
      higher risk of smoking compared with high (OR 8.76, 5.80)-alcohol drinking (OR
      5.42). Males were more likely to smoke than females (OR 4.56), perceived benefit
      on non-smoking-with the moderate and low perception having a greater chance of
      smoking compared with the higher level of perception (OR 2.31, 1.93). School
      level factors including type of school, health promoting school policy, student
      teacher ratio, proportion of teachers who smoked and availability of cigarettes
      near the school were also taken into account, but were not related to the status
      of smoking among the students. CONCLUSION: The present study confirmed that
      school factors had no significant relationship to smoking among youths. Strict
      smoke-free policy at school is recommended. School program should focus more on
      self-efficacy Social marketing campaign/ education should focus on friends and
      family as non-smoking role models.

PMID- 23130493
TI  - The urinary cotinine and serum 25 hydroxyvitamin D levels in male smokers.
AB  - OBJECTIVE: To assess urinary cotinine and the effects of smoking on 25(OH)D
      levels in 67 male smokers. MATERIAL AND METHOD: Urine and blood specimens were
      analyzed for cotinine and serum 25 hydroxyvitamin D (25(OH)D) concentrations by
      high performance liquid chromatography (HPLC) and chemiluminescent immunoassay,
      respectively. The accuracy, precision and detection limit of the HPLC method were
      also tested. RESULTS: The detection limit of urinary cotinine was 0.02 microg/ml.
      The recoveries of cotinine concentrations of 0.15-2.0 microg/ml were greater than
      95%. Only 23.9% of smokers had sufficient levels of serum 25(OH)D at least 30
      ng/ml. The smokers were divided into dairy co-operative smokers and other
      smokers. The average urinary cotinine concentrations of 1,421.42 and 1,866.52
      microg/g creatinine were not significant different in dairy co-operative smokers
      and other smokers whereas the average 25(OH)D of 29.09 and 22.65 ng/ml,
      respectively, were significantly different at p-value of < 0.001. CONCLUSION: The
      42.86% and 10.26% of the diary co-operative smokers and other smokers had
      sufficient serum 25(OH)D levels to prevent osteoporosis.

PMID- 23130494
TI  - Human capital identification process: linkage for family medicine and community
      medicine to mobilize the community.
AB  - BACKGROUND: Community diagnosis and approach has shifted from a professional
      focus to a community focus. The information system has also been developed to
      reflect socio-cultural information. This new system has been established
      throughout the country and is being recorded in the computer system. However
      these data still lack human capital information to promote community
      mobilization. OBJECTIVE: The present study aims to develop a process which
      reflects human capital from the insider and outsider points of view and which
      builds on the existing work system of primary care service, family medicine, and
      community medicine. MATERIAL AND METHOD: The present study applies the
      participatory action research design with mixed methods including community grand
      tour, household survey socio-metric questionnaire and focus group discussion in
      order to gather insider view of human capital. A key instrument developed in the
      present study is the socio-metric questionnaire which was designed according to
      the community grand tour and household survey results. RESULTS: The findings
      indicate that the process is feasible and the insider point of view given a
      longer evidence based list of the human capital. The model enhanced a closer
      relationship between professional and community people and suggested the
      realistic community mobilizer name list. CONCLUSION: Human capital identification
      process is feasible and should be recommended to integrate in the existing work
      process of the health staff in family and community practice.

PMID- 23130495
TI  - Job satisfaction and organizational citizenship behavior of personnel at one
      university hospital in Thailand.
AB  - OBJECTIVE: To investigate the relationship between job satisfaction and
      Organizational Citizenship Behavior (OCB) of the personnel at one university
      hospital in Thailand. MATERIAL AND METHOD: This cross-sectional descriptive study
      was conducted on 296 respondents who worked in the Office of the Dean, 13
      departments and 2 Offices of Research Center and Office of Community Medicine
      Center. All of them were personnel in one university hospital in Thailand. The
      Organizational Citizenship Behavior Questionnaire of Niehoff and Moorman using
      the five dimensions scale developed by Podsakoff and Mackenzie and Job
      Descriptive Index (JDI) were used for assessing job satisfaction. For inferential
      statistics, Pearson's product moment correlation coefficient was used for
      correlation. RESULTS: The percentage mean score of job satisfaction was 58.67 and
      subscale of job satisfaction was found that satisfaction with supervision held
      the highest of the mean score, while satisfaction with pay and promotion had the
      lowest and low of the mean score. The mean score of OCB was high and the facets
      of OCB was found that conscientiousness had the highest mean score and
      sportsmanship had the lowest. By using Pearson's Product Moment Correlation
      Coefficient to analyze the relationships between satisfaction and OCB, it showed
      that there were statistically significant low positive correlations between job
      satisfaction and OCB (r = 0.173, p < 0.01). CONCLUSION: The one university
      hospital executives should promote the pay, promotion and supervision factors
      which encourage personnel to be satisfied and demonstrate their OCB as their
      reciprocal reaction.

PMID- 23130496
TI  - Situational leadership styles, staff nurse job characteristics related to job
      satisfaction and organizational commitment of head nurses working in hospitals
      under the jurisdiction of the Royal Thai Army.
AB  - OBJECTIVE: To analyze the relationships between the situational leadership
      styles, staff nurse job characteristic with job satisfaction and organizational
      commitment of head nurses working in hospitals under the jurisdiction of the
      Royal Thai Army MATERIAL AND METHOD: The cross-sectional analytical study was
      conducted in 128 head nurses working in hospitals under the jurisdiction of the
      Royal Thai Army. Data were collected by mailed questionnaires. A total of 117
      completed questionnaires (91.4%) were received for analysis. Statistical analysis
      was done using Pearson's Product Moment Correlation Coefficient. RESULTS: It was
      found that situational leadership styles were not correlated with job
      satisfaction and organizational commitment of head nurses. Staff nurse job
      characteristics had a low level of positive correlation with job satisfaction and
      organizational commitment of head nurses at 0.05 level of significance (r = 0.202
      and 0.189 respectively). CONCLUSION: The hospital administrators should formulate
      policy to improve working system, human resource management and formulate
      policies and strategies based on situational leadership. In addition, they should
      improve the characteristics of staff nurse job by using surveys to obtain job
      satisfaction and organizational commitment.

PMID- 23130497
TI  - Development of a water-related disaster decision model for nurses in Thailand.
AB  - BACKGROUND: Disasters, be they natural or manmade, are catastrophic events that
      confront nursing managers with the challenge of acting to reduce the impact of
      such events upon society as a whole. OBJECTIVE: Provide nursing management
      personnel with a guide organized in such a fashion as to facilitate the decision
      making process in water related disasters. To develop a model to guide the
      decision-making process regarding water-related disaster management. MATERIAL AND
      METHOD: The combination of the two-round of modified Delphi method and The Simple
      Multi-attribute Rating Technique (SMART) was used to develop a decision tool.
      Thirty-four experts, including nurses, physicians and manager from three
      hospitals situated in previous disaster zones participated in this project.
      Delphi consensus was reached when the mean score of agreement was above 4.0 and
      standard deviation was below 1.0. Kendall's Coefficient of Concordance and the
      Kruskal Wallis H-test were performed to determine the degree of agreement and
      association of criteria rankings. RESULTS: The 36 variables were constructed with
      seven alternatives: policy, communications, materials, human resource management,
      operation effectiveness, health and stakeholder participation. An agreement in
      attribute ranking among the experts was found. The trade-off scores of model
      variables were presented to identify feasible arrays of disaster planning needs.
      CONCLUSION: The authors proposed a practical method to develop a decision model
      based on the input of key individuals in disaster management. The model can be
      used to guide the decision making for nurse managers resulting in the best
      practice for water-related disaster management.

PMID- 23130498
TI  - People living with HIV/AIDS in the city of Bangkok: quality of life and related
      factors.
AB  - OBJECTIVE: To assess the quality of life and factors related to quality of life
      among people living with HIV/AIDS in Bangkok, Thailand. MATERIAL AND METHOD: A
      cross-sectional survey research was conducted among 138 people aged over 18 years
      living with HIV/AIDS in Bangkok. The sample was selected by purposive sampling
      from HIV infected persons who attended the HIV clinic at the hospitals in
      Bangkok. Data were collected by self-administered questionnaires from June to
      July 2010 and analyzed by frequency, percentage, mean, standard deviation, Chi
      square test and Pearson Product Moment Correlation Coefficient. RESULTS: The
      finding revealed that of the people living with HIV/AIDS, 67.4% reported a
      moderate level with respect to quality of life and 32.6% reported a good level
      concerning the quality of life. Factors related to quality of life were age,
      education level, monthly income, self-esteem,family relationships and social
      support (p < 0.05). CONCLUSION: All of the people living with HIV/AIDS reported
      having a moderate to good quality of life. From research results, responsible
      organizations should establish activities to promote self-esteem, family
      relationships and social support for people living with HIV/AIDS to enhance the
      quality of life of infected persons. Increasing public awareness to better
      understand basic needs such as family relationships and social support and
      providing HIV/AIDS education to the community were deemed important.

PMID- 23130499
TI  - The geographical distribution of allele polymorphisms of Plasmodium vivax in
      different regions of Thailand.
AB  - OBJECTIVE: To investigate the genetic structure of Plasmodium vivax
      circumsporozoite surface protein (PvCSP) and P. vivax merozoite surface protein 1
      (PvMSP1) genes from field isolates of malaria parasites from four different
      regions of Thailand. MATERIAL AND METHOD: The data was collected by cross
      sectional survey, consisting of 273 P. vivax infected blood samples from malaria
      clinics in 4 different border regions of Thailand from February 2008 to February
      2009. The dried blood spots were extracted for DNA and Plasmodium species
      confirmed by species-specific primer sets. PvCSP and PvMSP1 genes were amplified
      and their population genetics were analyzed by using the Heterozygosity (H)
      formula, F-STAT and LIAN programs. RESULT: There was considerable variation in
      the PvMSP1 gene within 2 fragments for which HE was 0.8303, whereas PvCSP showed
      low HE at 0.1418. Significant differences in allele frequencies between sites
      were quantified by Fst, Linkage disequilibrium (LD). The results showed PvMSP1
      F2; Fst = 0.063, p = 0.07; PvMSP1 F2 RFLP pattern; Fst = 0.154, p = 0.005; PvMSP1
      F3; Fst = 0.23, p = 0.005 and the overall loci showed Fst = 0.151, p = 0.005
      (Fisher's exact test). All values of Index association (I(S)A) were non
      significant. There was no evidence of LD within the P. vivax populations.
      CONCLUSION: H(E) at each locus of the PvMSP1 gene showed significant differences
      in allele frequencies between sites.

PMID- 23130500
TI  - Factors associated with depression among Thai female workers in the electronics
      industry.
AB  - OBJECTIVE: To determine the factors associated with depression among female
      workers in the electronics industry. MATERIAL AND METHOD: A cross-sectional study
      was performed during the period of March 2010. A sample of 444 females working in
      the electronics industry-located in Ayutthaya province, Thailand-were selected by
      stratified random sampling. Data were collected by a self-administered
      questionnaire. Depression was assessed through utilization of the Center
      Epidemiologic Studies Depression scale (CES-D). Data regarding socio
      demographics, employment history, personal crises, family relationships, effort
      reward imbalance and personal resources were included to assess all factors
      influencing depression. Logistic regression analysis was used to analyze the
      predictability of factors. RESULTS: The prevalence of depression in female
      workers was 28.8%. Multiple logistic regression analysis showed that those with
      poor family relationships, low reward and poor social support had 5.83 times (95%
      CI: 2.66-12.79), 2.58 times (95% CI: 1.20-5.53) and 4.63 times (95% CI: 1.60 to
      13.40) higher risk of suffering from depression, respectively. CONCLUSION: The
      results suggest that improving family relationships, rewards and social support
      can be important strategies in the prevention of depression in female workers.
      Surveillance on depression in female workers should be conducted in the industry.
      Existing rewards should be reviewed and family relationships and social support
      should be enhanced, in order to decrease the impact of depression in female
      workers.

PMID- 23130501
TI  - Chewing of betel quid: why do health careproviders in Thimphu, Bhutan, do it?
AB  - OBJECTIVE: This cross-sectional study aimed to determine the prevalence of betel
      quid chewing and related factors including general characteristics, behavioral
      pattern, perception and social influences among health care providers in Thimphu,
      Bhutan. MATERIAL AND METHOD: A self-administered questionnaire was handed to 478
      health care providers working in different units of health care centers in
      Thimphu during June-July 2010. A total of 391 (81.8%) questionnaires were
      returned. Chi-square test and multiple logistic regression were applied. RESULTS:
      The prevalence of current betel quid chewers among this group was 26.6%. Males
      chewed betel quid more than females (29.5%, 23.9% respectively). Forty-two
      percent of current chewers had no specific reasons for chewing betel quid,
      although 18.2% declared that they were addicted. Both friends and family members
      were key persons involved in influencing betel quid chewing. Marital status was
      significantly associated with betel quid chewing, married health care providers
      being 2 times more likely to chew betel quid (OR = 2.09, 95% CI = 1.02-4.28) than
      those of single marital status. Similarly, those coming from West Bhutan, were 2
      times more likely to be currently using betel quid (OR = 2.71, 95% CI = 1.32
      5.55) than other regions. Health care providers from families with more than half
      of their members chewing betel quid were 14 times more likely to be currently
      chewing it (OR = 14.52, 95% CI = 6.02-35.04) than families having none of their
      members chewing it. Health care smokers were more likely to chew betel quid than
      non-smoking ones (p-value = 0.012). Also occasional drinkers were 3 times more
      likely to be currently using betel quid (OR = 3.52, 95% CI = 1.78-6.96). Those
      who perceived a high barrier to quit chewing were about 2.6 times more likely to
      be current chewers of betel quid, than those who perceived less of a barrier to
      quit (OR = 2.62, 95% CI = 1.21-5.67). CONCLUSION: The present study revealed
      betel quid chewing prevalence rate of 26.6%. Of the various factors considered
      under study, marital status, region of origin, family members chewing betel quid,
      status of smoking and drinking were statistically proven significant.

PMID- 23130502
TI  - Exposure to trinitrotoluene and health effects among workers in an artillery and
      ammunition plant.
AB  - OBJECTIVE: To determine urinary trinitrotoluene (TNT), 2-amino-4, 6
      dinitrotoluene (2ADNT) and 4-amino-2, 6-dinitrotoluene (4ADNT) and health effects
      upon workers in an ammunition plant. MATERIAL AND METHOD: The urine samples from
      forty munition workers and forty office workers were monitored for TNT and its
      metabolites by gas chromatography-mass spectrometry. The workers were interviewed
      with a questionnaire. RESULTS: The median levels of TNT and its metabolites were
      112.84 and ranged from non-detectable (ND) to 1,833.81 mg/L. Median levels for
      2ADNT were 11.66, ranging from ND to 360.89 mg/L. Median levels for 4ADNT were
      19.95 and ranged from ND to 314.28 mg/L. There were significant correlations
      between TNT and 2ADNT in urine (r = 0. 700, p-value < 0.001), as well as for TNT
      and 4ADNT (r = 0.783, p-value < 0.001). Exposed workers reported eye, nose and
      throat irritations, weakness and headaches with considerably higher frequency
      than non-exposed workers. CONCLUSION: TNT levels in urine were strongly
      associated with 4ADNT and 2ADNT levels. Workers exposed to TNT complained of
      nose, throat and eye irritation, along with overall weakness and headaches.

PMID- 23130503
TI  - Microbial counts and particulate matter levels in indoor air samples collected
      from a child home-care center in Bangkok, Thailand.
AB  - OBJECTIVE: To assess the microbial count (bacteria and fungi) and particulate
      matter with sizes less than 10 microm (PM10) level in indoor air of a child home
      care center in Bangkok. MATERIAL AND METHOD: A total of 287 air samples were
      collected from the indoor air of twenty households which were part of a child
      home-care center to assess bacterial and fungal counts (212 samples) and PM10
      levels (66 samples). Additionally, fifty-two and twenty-six outdoor air samples
      were collected to compare microbial count and PMo10 levels. RESULTS: It was found
      that means + standard deviation (SD) for bacterial and fungal counts in the child
      home-care center were 527.8 +/- 230.9 cfu/m3 and 514.6 +/- 256.7 cfu/m3,
      respectively (those in outdoor air samples were 264.6 +/- 179.7 cfu/m3 and 308.7
      +/- 217.3 cfu/m3, respectively). The mean +/- SD of PM10, level was 125.1 + 48.0
      pg/m3 (that in outdoor air samples was 120.1 +/- 66.9 microg/m3). When compared
      with the levelfor the indoor air quality guideline, 47.2% and 47.6% of total air
      samples had bacterial and fungal counts higher than the recommended levels and
      47.0% of total air samples had PM10 levels higher than the recommended level.
      CONCLUSION: The present study found that about 47% of total air samples collected
      from the child home-care center had bacterial and fungal counts and PM10 levels
      higher than the recommended levels. These results may affect the health of a
      child who spends most of his/her time in this center Some intervention or
      preventive endeavors should be undertaken, including periodic cleaning and
      maintenance of the ventilation systems and adoption of a regular schedule for
      room cleaning should be implemented.

PMID- 23130504
TI  - Exposure to particulate matter, CO2, CO, VOCs among bus drivers in Bangkok.
AB  - OBJECTIVE: To measure the exposure of particulate matter CO2, CO, VOCs among
      Bangkok Mass Transit Authority (BMTA) Bus Drivers. MATERIAL AND METHOD: The
      exposure of 60 bus drivers to PM2.5, PM10, VOCs, CO2, CO was monitored for full
      shifts on three routes of air-conditioned (A/C) and non-A/C buses. RESULTS: The
      average PM2.5 exposure concentrations among non-A/C bus drivers (323.81 mg/m3)
      were significantly higher than that of A/C bus drivers (206.46 mg/m3) (p-value =
      0.016). The average benzene, toluene and xylene exposure concentrations were
      429.15, 225.11, 127.60 mg/m for non-A/C bus drivers. The average CO2 levels in
      A/C buses were significantly higher than those in non-A/C buses (p-value <
      0.001). The CO levels in non-A/C buses were significantly higher than those in
      A/C buses (p-value = 0.037). CONCLUSION: The bus drivers were exposed to high
      concentrations of air pollutants. The increase of ventilation and cleaning of
      buses will reduce the exposure of air pollutants.

PMID- 23130505
TI  - Antioxidant activity comparison of walnuts and fatty fish.
AB  - BACKGROUND: Walnuts and fatty fish contain high amounts of polyunsaturated fatty
      acids, which have been shown to decrease the incidence of cardiovascular disease.
      Walnuts and fatty fish also contain other nutrients, such as antioxidants, that
      contribute to the reduction of cardiovascular disease. OBJECTIVE: The purpose of
      the present study was to compare the effects of dietary walnuts and fatty fish on
      the plasma and urine oxygen radical absorbance capacity (ORAC) values. MATERIAL
      AND METHOD: Twenty-five subjects participated in this randomized 3 x 3 crossover
      study, which was performed under controlled metabolic feeding conditions.
      Subjects consumed 3 isoenergetic diets and each diet was consumed for 4 weeks: a
      control diet (no nuts or fish), a walnut diet (1.5 oz/day of walnuts, 6
      times/week) and a fish diet (8 oz/week of salmon). Blood specimens were collected
      at baseline and at the end of each diet period. RESULTS: The results showed that
      the plasma hydrophilic ORAC was significantly higher in the walnut diet compared
      with the control diet and the fish diet (p < 0.0001). In addition, the urine ORAC
      was significantly higher in the walnut diet and the fish diet compared with the
      control diet (p < 0.0001). Moreover the hydrophilic/lipophilic ORAC for the food
      itself was significantly higher in the walnut diet compared with the control diet
      and the fish diet (p < 0.0001). CONCLUSION: The present results suggest that
      walnuts have a large antioxidant capacity; therefore, including walnuts in the
      daily diet may be beneficial to maintain an antioxidant status in the body.

PMID- 23130506
TI  - Effects of radiation and SAR from wireless implanted medical devices on the human
      body.
AB  - OBJECTIVE: To study the effect and impact from electromagnetic field radiation
      and specific absorption rate (SAR) on the human body. MATERIAL AND METHOD: The
      present study describes a quasi-experimental research. The implanted antenna
      embedded to the medical device such as the cardiac pacemaker was designed in the
      human phantom using finite-difference time-domain method. The skin mimicking gels
      were developed as the tissue stimulant to realistically represent the human body.
      RESULTS: The dual-band implantable antenna is designed to operate at 400 MHz and
      2.4 GHz and is used to determine the level of electromagnetic field radiated and
      SAR levels from implanted biosensors. The SAR limitations, maximum gain, maximum
      temperature rise in the body model and the radiation efficiency on each operating
      frequency are determined to provide the safety level. CONCLUSION: The research
      results indicate that SAR and safety limitations are body and frequency
      dependent. High-performance and low-operated power dual-band PIFA antenna for
      development of the next generation of medical implants operating on the MICS and
      the ISM bands will facilitate clinically significant improvements in healthcare.

PMID- 23130507
TI  - [Some problems of modern gerontology and geriatrics in the Russian Federation:
      the sight of the clinical physician].
AB  - This article presents some problems of modern Russian gerontology and geriatrics
      by eyes of the scientist--the clinical physician having long-term experience in
      the field. Educational, scientific, practical aspects of gerontology and those
      stereotypes of understanding of problems of elderly which developed for years are
      subjected the certain criticism, decades, but in the modern world any more
      absolutely correspond to a today's reality. It is offered to transform the
      ideology of the major directions of gerontology, having put at the head of a
      corner not ideas of prolongation of life as that and carrying out basically
      actions in relation to seriously ill, but improvements of quality of life,
      preventive maintenance and treatment of set of the age-related diseases,
      overcoming of the developed practice of the relation to elderly and senile
      patients as to persons dependent and demanding the constant help. The author
      urges the public health governing bodies to reconsider the norms of the geriatric
      help existing for many years but not meeting modern requirements in the
      conditions of polyclinic and a hospital and to make more clear and claimed by a
      society the possibilities and achievements of gerontology.

PMID- 23130508
TI  - [Gerontodietology].
AB  - Gerontodietology is one of the most important parts of dietetics studying
      problems of nutrition of elderly and old persons and persons with high risk of
      early and pathological aging, developing principles of rational nutrition,
      prophylactic and curative nutrition and methods of its organization. Functional
      structure of modern gerontodietology, its scientific-methodical bases,
      terminological features are presented. Composition and features of healthy
      nutrition of elderly people is described in details, methods of its optimization
      and individualization are given. Notions of geriatric dietotherapy, its principal
      difference from curative nutrition of patients of other ages are described. Large
      section of the article is devoted to the modern problems of prophylactic
      gerontodietology, intended more for persons with high risk of early aging than
      for elderly persons. Theoretic basis and methodological contents of prophylactic
      gerontodietology are presented; practical recommendations on dietetic means to
      prevent intensive development of involution processes and organic pathology in
      the body are described.

PMID- 23130509
TI  - [The role of oxidative stress in skin aging].
AB  - The review covers the literature proving that ROS formation in aging overbalances
      the antioxidant defense system potential of the skin structure (horny layer,
      epidermis and dermis). It has been shown that ROS are involved in the
      pathogenesis of inflammatory processes and allergic responses in the skin. The
      role of ROS and antioxidant systems in the cell-mediated responses associated
      with the MAP kinase activity in the skin is discussed. Special attention is paid
      to the ultraviolet irradiation exposure, which accounts for its genotoxic,
      immunosuppressive and carcinogenic effects on the skin.

PMID- 23130510
TI  - [All-cause mortality among men of elderly and senile age depending on day of
      week, a season and changing to daylight saving time for a 13-year period].
AB  - To study the all-cause mortality among men of elderly and senile age depending on
      day of week, month of year, a season, changing to daylight saving time,
      prospective supervision over 1067 men of 60 years and upward for a 13-year period
      was conducted. The all-cause mortality depending on transition into daylight
      saving time was counted for March and October and compared to indicators of April
      and November accordingly. The all-cause mortality rate had made 1668,5 on 1000.
      This indicator in January (177.9 per 1000) and August (175.2 per 1000) was
      higher, than in November (102.4 per 1000; p < 0.05). Dependence of all-cause
      mortality rate on day of week, a season, changing to daylight saving time was not
      revealed. The analysis of all-cause mortality rate on days of week in various
      seasons has revealed that in autumn the greatest all-cause mortality rate was
      observed on Sunday (83.6 per 1000), the least--on Monday (35.0 per 1000).
      Besides, on Monday the greatest all-cause mortality rate was observed in winter
      (35.5%, or 72.8 per 1000), and the least one--in autumn (17.1%, or 35.0 per
      1000). During other moments of supervision statically significant distinctions
      were not revealed.

PMID- 23130511
TI  - [Influence of polyorgan pathology on the biological age of male and female
      patients of different calendar age].
AB  - The research was executed on 1433 patients, male (1055) and a female (378), of
      calendar age from 17 to 93 years with a various polyorgan somatic and
      psychoneurological pathology in remission. The polyorgan pathology worsens age
      dependent indicators and increases the bioage of male and female patients. Thus
      sexual differences exist and practically disappear with the years. In men the
      polyorgan pathology makes negative influence on the age-dependent indicators in a
      greater degree and increases the bioage. This may be a cause of lower life
      expectancy for men compared with women.

PMID- 23130512
TI  - [Molecular-cellular mechanisms of retina pathology development in people of
      various age].
AB  - The review considers the molecular-cellular mechanisms of retina pathology in
      people of various age. Dysfunction of retinal cells (retinal pigment epithelium,
      photoreceptors, neurons) causes the development of age-related macular
      degeneration, retinal ischemia and a variety of hereditary diseases. This is the
      description of involvement of genes and signaling molecules in the dysfunction of
      retinal cell types. It is established that a breach of RPE65 gene expression
      leads to age-related macular degeneration, retinitis pigmentosa and Leber's
      congenital amaurosis. Mutations in the CRX gene are the cause of progressive
      states such as cone-rod dystrophy. In addition, more than 100 mutations in RHO
      have been identified, leading to different variants of retinitis pigmentosa. The
      involvement of TGF-(beta2 in the formation of retinal cells and the regulation of
      secretion of vascular endothelial growth factor VEGF, which synthesis is
      increased by ischemic lesions of the retina, is described.

PMID- 23130513
TI  - [The role of melatonin in progress of pathology of a retina in patients of senior
      age group].
AB  - Epiphysis cerebri and its hormone melatonin play a leading role in aging.
      Melatonin affects many biochemical processes in a human body. The authors assume
      that there is a correlation between the level of melatonin and development of
      macular degeneration by age.

PMID- 23130514
TI  - [Age-related changes of 6-sulphatoxymelatonin excretion in stomach and colorectal
      cancer patients].
AB  - Circadian rhythm of 6-sulphatoxymelatonin (aMT6s) excretion has been studied in
      stomach cancer (n = 89) and colorectal cancer (n = 86) patients. The excretion of
      aMT6s was decreased in cancer patients. The disturbances of the circadian rhythm
      of aMT6s excretion have been observed in the cancer patients as well. These
      changes were directly proportional to the extent of cancer process and to the
      extent of lymphogenic metastasis.

PMID- 23130515
TI  - [Age-dependent changes in phospholipid content and neutral lipid contents in
      aging].
AB  - Oxidative processes and lipid metabolism in young (3-4 months) and old (25-28
      months) were studied. The increase of the rate of reactions of free radical
      oxidation of lipids (hydroperoxides, and malondialdehyde) and the accumulation of
      products of oxidative modification of proteins was recorded in mitochondrial
      fraction of rat brain. The accumulation of nitric oxide in the mitochondria and
      the oxidation products leads to the development of oxidative stress.
      Investigation of the lipid spectrum in old rat brains showed that aging was
      accompanied by a change in the qualitative and quantitative content of
      phospholipids. A change in the metabolism of neutral glycolipids leads to a
      decrease in the content of cerebrosides and sulfoserobrosides. At the same time
      an increase in sphingosine (a product of hidrolytic decomposition of neutral
      glycolipids) was observed. The key role of lipid metabolism in age pathologies
      was noticed.

PMID- 23130516
TI  - [Tissue oxygen exchange and oxidative processes in long-livers: age
      peculiarities].
AB  - This work was undertaken to study tissue oxygen exchange and oxidative processes
      in the long-lived individuals who were assumed as the physiologically aging
      individuals. Oxygen tension was assessed in forearm subcutaneous cellular tissue
      by means of the polarographic method while performing 10 min oxygen inhalation
      tests (with spontaneous oxygemogram recording) and a 10 min clamping of vessels.
      The obtained data served as the tissue oxygen exchange indicator. This approach
      made us possible to evaluate the oxygen delivery and oxygen uptake. To study
      qualitative characteristics of oxidative processes, we assessed vacat-oxygen of
      the blood and urine and estimated the underoxidation coefficient proposed by
      Muller. We have found that tissue respiration intensity falls, the amount of
      underoxidated products of the blood and urine rises, and the underoxidation
      coefficient increases in aging. The decrease of tissue oxygen respiration
      intensity in subcutaneous cellular tissue reflects the development of tissue
      hypoxia associated with reduced activity of the enzymes, being involved in oxygen
      exchange. An age-related decrease of tissue perfusion leads to the formation of
      circulatory hypoxia and also contributes considerably to tissue hypoxia
      formation. The revealed changes in the tissue oxygen exchange and oxidative
      processes in the long-livers are generally correspondent to those that can be
      seen in the people of 80-89 years. This finding speaks in favor of the
      physiological aging in the long-livers.

PMID- 23130517
TI  - [New approach to gait disorders therapy in late stages of Parkinson's disease].
AB  - We conducted an open noncontrolled study of efficacy of repetitive transcranial
      magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC)
      combined with acetylcholinesterase inhibitor (galantamine) therapy in 30
      Parkinson's disease patients with cognitive impairment and higher level of gait
      disorders. Galantamine dose gradually increase to maximum of 16 mg/day (8 weeks)
      before rTMSand after that we start rTMS for 10 consecutive days. Cognitive,
      neuropsychiatric and motor symptoms were assessed clinically at baseline and at
      end of 10 weeks combined therapy using the Mini Mental State Examination (MMSE),
      Freezing Of Gait (FOG), Clinical Gait And Balance Scale (GABS), Tinetti scale,
      the clock drawing test, the Frontal Assessment Battery (FAB), PDQ-39 and Beck
      Depression Inventory (BDI). The metabolism in the frontal lobes, caudate nucleus,
      thalamus were assessed in 9 patients at baseline and end of rTMS by [18F]FDG-PET.
      Changes in total point scores on the scales at the ends of 10 weeks were compared
      with the baseline. Results were significant in the FOG (p = 0.00002), GABS (p =
      0.000006), MMSE (p = 0.0001), FAB (0 = 0.003), PDQ-39 (p = 0.00009), BDI (p =
      0.00004). Improvements in gait and decreases in freezing and falls were seen in
      the end of study period. Our study demonstrated the beneficial effect of rTMS of
      the DLPFC combined with acetylcholinesterase inhibitor treatment on metabolism in
      the frontal lobes, caudate nucleus, thalamus ([18F]FDG-PET), improving of gait
      and cognitive functions in PD patients.

PMID- 23130518
TI  - [Discurculatory encephalopathy at the elderly Republics Sakhas (Yakutia)].
AB  - The clinic-etiological characteristic of discirculatory encephalopathies (DE)
      depending on residing region was studied. The analysis of risk factors has shown
      that the leading reasons of vascular defeat of a brain in all patients were the
      atherosclerosis and an arterial hypertensia, thus in patients living in good
      ecologically situation these risk factors were present less often. Clinical
      symptoms of DE, as well as numerous subjective and clinical displays, were most
      expressed in patients of the basic group, inhabitants of ecologically adversed
      Viljujsky region.

PMID- 23130519
TI  - [Combined therapy of membranoproliferative glomerulonephritis in older patients].
AB  - The aim of the study was to investigate the effectiveness of combined long-term
      therapy by cytostatics and steroid hormones in older patients with
      membranoproliferative glomerulonephritis to halt renal failure progression. 27
      patients older than 60 years with morphologically proved membranoproliferative
      glomerulonephritis have been treated. Nephrosclerosis was detected in 40% of
      studied patients according to results of kidney biopsies. The mean age of the
      patients was 65.8 +/- 1.5 years. The activity of the disease depended on presence
      and severity of nephrotic syndrome. 17 (62.9%) patients had coronary heart
      disease, 7 (25.9%) patients had chronic bronchitis, 7 (25.9%) patients had peptic
      ulcer disease in a remission phase. Patients received therapy by cyclophosphamide
      in a dose of 2 mg/kg daily and prednisolone in a dose of 1 mg/kg daily during 2
      years. Tolerability of assigned treatment was satisfactory. The main clinical and
      laboratory signs of nephrotic syndrome were significantly reduced and the proof
      remission was reached after 8-12 months of combined therapy. During the
      observation (24 month) the glomerular filtration rate in studied patients didn't
      decreased over 30-59 mL/min/1.73 m2 and corresponded to stage 3 of chronic kidney
      disease.

PMID- 23130520
TI  - [Possibilities of pharmacological correction of the arterial hypertension in
      elderly patients with gout].
AB  - The aim of this work was a detailed study of questions connected with the
      peculiarities of circadian blood pressure profile, efficiency of amlodipine in
      elderly patients with gout and arterial hypertension. We used 24-hour blood
      pressure monitoring before and after 3 and 6-months treatment. Patients with gout
      showed the disturbances of circadian blood pressure profile. Prolonged calcium
      antagonists are the best drugs for the hypertensive patients with gout.

PMID- 23130521
TI  - [Depressive frustration at vascular diseases of a brain in patients of elderly
      and senile age].
AB  - According to inspection of 206 patients of 60 years old and elder on the basis of
      neurologic department of the Geriatric Center of Republican Hospital No 3 high
      prevalence of depression of small and average degree in the persons of advanced
      age suffering from cerebrovascular diseases is revealed. To estimate the
      expressiveness of depression the Hamilton's scale including 17 parameters was
      used.

PMID- 23130522
TI  - [Comparative effects of difluoromethylornithine and tincture of Siberian ginseng
      root on radiation carcinogenesis and life span in rats].
AB  - Influence of alpha-difluoromethylornithine (DFMO) and tincture of Siberian
      ginseng root (TSGR) on radiation carcinogenesis and life span in rats has been
      studied. The results of the study demonstrate that DFMO as well as TSGR
      significantly improved survival and decreased incidence and multiplicity of
      malignant and benign tumors in rats subjected to ionizing radiation. Beneficial
      effect on the rat survival rate and anticarcinogenic action of DFMO were more
      expressed compared with TSGR.

PMID- 23130523
TI  - [Influence of recanalization of chronic total occlusion of the left anterior
      descending artery on heart failure in elderly patients].
AB  - In article, analysis has been carried out on the influence of recanalization of
      chronic total occlusion of left anterior descending artery on the course of heart
      failure in elderly patients who had damage to a single artery and viable
      myocardium. Recanalization of chronic occlusion of left anterior descending
      artery together with conservative therapy in elderly patients improves the
      clinical course of heart failure. A more significant improvement seen in patients
      with chronic occlusion of left anterior descending artery without history of
      myocardial infarction.

PMID- 23130524
TI  - [On the issue of improving health care organisation for retirement age population
      (the Nizhny Novgorod experience)].
AB  - The article presents a detailed analysis of health care provision to both general
      and retirement age population (RAP) in the Nizhny Novgorod region. For the past
      10 years, the organization and use of different types of health care for RAP have
      not changed. The availability of inpatient health care for RAP is high whereas
      the availability of nursing and outpatient health care is low and palliative care
      service is not available. In order to enhance availability and ensure quality of
      medical services it is necessary to implement restructuring of health care for
      RAP at the municipal level herewith a key attention will be paid to out-patient
      types of health care expansion and palliative care development. The authors
      formulate some proposals aimed at improving the organization of medical and
      social care for RAP which should be included in the health care restructuring
      program at the municipal level.

PMID- 23130525
TI  - [Age-related peculiarities and determinating factors of atrial fibrillation].
AB  - The principal aim of the study was to investigate the causes and clinical
      features of atrial fibrillation (AF) in patients of two age groups--(1) 40-59
      years and (2) 60 and elder. 454 male and female patients of the cardiology
      department were studied. This article discusses recent concepts of the mutual
      influence of AF and associated clinical cardiovascular conditions and their
      complications. The duration and degree of correction of cardiovascular pathology
      and its correlation with the incidence of AF are evaluated.

PMID- 23130526
TI  - [Psycho-physiological peculiarities of stomatologists aged 50-65 with essential
      hypertension].
AB  - The article presents the results of studying of psycho-physiological
      peculiarities in stomatologists in the age before 65, that is actual in modern
      medicine. Certain specificity of psycho-physiological indices in stomatologists
      with essential hypertension is shown. The proposition is justified that
      alexithimia and susceptibility to illnesses of psychosomatic origin
      (particularly, essential hypertension) in stomatologists are essentially
      influenced by withdrawal, absence of inclination to partnership, cooperation,
      compromise at solution of problems and in conflict situations, and irresponsible
      attitude to other people, reduced empathy and sympathy to other people.

PMID- 23130527
TI  - [Peculiarities of professional burnout of anaesthetists-experts in resuscitation
      in various age periods].
AB  - The article is devoted to consideration of the problem of professional burnout
      with anaesthetists-experts in resuscitation in various age periods that is very
      actual in modern medicine. It is shown that peculiarity of the doctors' activity
      provokes formation of professional burnout in them. Psycho-emotional tension born
      by the sense of responsibility before the patients determines formation of
      responsible attitude of the doctors towards therapy, but it also has negative
      consequences in concern with disorder of homeostatic balance and unreasonable
      energetic expenditure. It is proved that formation of professional burnout in
      anaesthetists-experts in resuscitation has age specificity. At the age of 30-55
      it develops according to two subfactors: motivational-adjusting (reduction of
      professional achievements) and depersonalizational-derealizational one. Doctors
      at the age of 56-68 expose asthenic symptomatology of professional burnout.

PMID- 23130528
TI  - [Cognitive impairment in elderly patients with acute hypertensive
      encephalopathy].
AB  - Acute hypertensive encephalopathy in elderly patients appears reversible mild
      cognitive impairment. The erythrocyte sedimentation rate and blood creatinine
      measured during a hypertensive crisis are predictors of decline of visual-spatial
      orientation after two weeks of treatment.

PMID- 23130529
TI  - [Comparative analysis of mood disturbances among elderly with chronic leukemia
      and dyscirculatory encephalopathy].
AB  - Mood disturbances frequently transform clinical state of a disease that demands
      the essential consideration during medical treatment and the following
      rehabilitation. The current research deals with the study and comparison the
      psychological dysfunctions among elderly with chronic leukemia (CL) and
      dyscirculatory encephalopathy (DE). One hundred persons with CL were examined.
      Representative group numbered 85 patients with DE at I and II stages. Spielberger
      Khanin anxiety scale and Zung depression scale were used in this study. In the
      absence of DE clinical features the mood disturbances occurred as an anxiety for
      the patients with CL, while the combination of DE with CL led to depression. The
      elderly with DE have been characterized with anxiety and depression that is
      caused by cerebral ischemia.

PMID- 23130530
TI  - [Possibility of operative treatment of geriatric patients with critical lower
      limb ischemia].
AB  - The experience of treating 106 patients of 70+ years shows the possibility of
      successful vascular reconstructive procedures with good immediate and long-term
      results, even in the presence of critical limb ischemia and severe comorbidity in
      geriatric patients, if not guided by the principle of maximum revascularization
      of the affected limbs, and minimally sufficient, through a wide use of atypical
      and small renovations. In addition, not only comprehensive assessment of the
      reserve and compensatory capacities of the patients is important, but also
      preoperative prevention of cardiac, pulmonary and other complications.

PMID- 23130531
TI  - [Pension reform and potential occupation of elderly population at Ukraine].
AB  - The paper deals with the global issues relative pension reforms in Ukraine and
      worldwide. The author has outlined the main factors limiting occupation of older
      people. Second, measures to maintain their economic activity are proposed.

PMID- 23130532
TI  - [Interrelation of the internal picture of illness and valuable orientations in
      elderly patients with the type II diabetes].
AB  - Type 2 diabetes is a common endocrine disease of advanced age. Extraordinary
      prevalence of this disease requires the improvement of preventive measures. The
      authors emphasize the importance of study of psychosomatic mechanisms of disease,
      personality traits and possibilities of social functioning in the disease.
      Attempts to study the influence of value orientations on variants of the
      patient's social and physical functioning were undertaken. This may be
      particularly significant in the management of elderly patients with type 2
      diabetes as the role of age-value categories becomes one of the key. However
      studies of value orientations in elderly patients are scarce. It can be assumed
      that a more detailed study of value characteristics of elderly patients with type
      2 diabetes will not only improve the quality of diagnosis, treatment and
      prevention, but also may be one of the important stages of psychotherapy. The aim
      of the work was to study the influence of value orientations on the inside
      picture of the disease in elderly patients with type 2 diabetes.

PMID- 23130533
TI  - [The natural peptide geroprotector antiarhythmic action].
AB  - The research of biological activity of peptide geroprotector Slavinorm on the
      basis of calf aorta extract was conducted in experimental models of hypertension
      and chloride-calcium arrhythmia. The research results showed that in experimental
      model of arrhythmia in rats induced by pituitrin administration, intraventricular
      and intramuscular introduction of Slavinorm in therapeutical dose had caused to
      leveling of hypertension symptoms. That was expressed in normalization of blood
      pressure characteristics, body weight, heart and kidney weight. In the
      experimental model of chloride-calcium arrhythmia in rats inrtaventricular and
      intramuscular introduction of Slavinorm showed the ability to predict the
      arrhythmia development caused by the Calcium Chloride administration. The
      research results testify to availability of the medication research in the
      capacity of the medication for treatment of age related pathology conditioned by
      vessels impaired function.

PMID- 23130534
TI  - [The effect of the amino acid combinations on cell proliferation in tissue
      cultures in old rats].
AB  - In organotypic tissue culture, the effect of the 20 coded amino acids
      combinations, in the effective concentration of 0.05 ng/ml, on the cell
      proliferation development in the spleen, myocardium, pancreas and brain cortex
      explants in 24 months rats was investigated. The combinations of two amino acids
      (stimulating and inhibiting proliferation) produced in the tissue culture the
      stimulating effect, exceeding by 8-10% as compared to the isolating effect of the
      stimulating amino acid. The results obtained form the base for the further
      synthesis of new effective dipeptides to be used to increase the regeneration of
      tissues when aging.

PMID- 23130535
TI  - Diagnosis and management of new-onset hoarseness: a survey of the American
      Broncho-Esophagological Association.
AB  - OBJECTIVES: The recently published Clinical Practice Guideline raised issues
      related to the value and timing of laryngoscopy in patients with hoarseness. We
      sought to determine the extent to which these guidelines concur with clinical
      practice among members of the American Broncho-Esophagological Association
      (ABEA). METHODS: A web-based survey was distributed to ABEA members, composed of
      four sections: 1) background and demographics; 2) information regarding the
      appropriate length of time that new-onset dysphonia may be managed before
      laryngeal visualization, given particular comorbidities; 3) the frequency and
      risks of office-based flexible transnasal laryngoscopy; and 4) the overall value
      of laryngoscopy and stroboscopy. RESULTS: Seventy-one ABEA members completed the
      survey; they had a combined 1,468 years of post-residency experience.
      Approximately 75% of respondents were involved in a fully academic practice.
      Across all respondents, an average of 11 patients with new voice complaints were
      seen per week. Overall, 98.6% of respondents believe that laryngoscopy is very
      valuable. Stridor in a neonate and potential foreign bodies were both conditions
      necessitating laryngoscopy on the day of presentation. In patients with no
      serious underlying condition(s), the mean duration until laryngoscopy was 12.96
      days (range, 0 to 30 days). CONCLUSIONS: These data suggest that the current
      practice patterns among experts in the field are divergent from the recently
      published Guideline.

PMID- 23130537
TI  - Selective vestibular neurolabyrinthitis of the lateral and superior semicircular
      canal ampulla and ampullary nerves.
AB  - OBJECTIVES: The diagnosis of vestibular neurolabyrinthitis is based on the sudden
      appearance of vertigo that lasts for hours or days without associated cochlear or
      central nervous system signs or symptoms. The advent of the video head impulse
      test, cervical vestibular evoked myogenic potential testing, and ocular
      vestibular evoked myogenic potential testing has provided interesting clinical
      evidence for evaluating and monitoring the damage to specific compartments of the
      vestibular apparatus. These various methods of testing individual end-organ
      functions may have a clinical impact on the vestibular workup of
      neurolabyrinthitis. METHODS: This report describes 3 patients with acute
      vestibular neurolabyrinthitis in whom caloric tests, cervical vestibular evoked
      myogenic potentials, ocular vestibular evoked myogenic potentials, and the video
      head impulse test led to a suspicion of peripheral vestibular deficits of the
      lateral or superior semicircular canal ampulla or ampullary nerves. RESULTS: In
      our patients, the examination results (normal hearing, absence of responses on
      caloric testing, and bilateral preservation of cervical and ocular vestibular
      evoked myogenic potentials) disclosed an acute partial superior vestibular
      neurolabyrinthitis. CONCLUSIONS: To our knowledge, these are the first reported
      cases in which selective damage to the lateral and superior semicircular canals
      and their nerves caused by neurolabyrinthitis was demonstrated clinically. Our
      clinical results indicate that the damage can be selective for specific
      vestibular end organs.

PMID- 23130536
TI  - Transoral robot-assisted lingual tonsillectomy and uvulopalatopharyngoplasty for
      obstructive sleep apnea.
AB  - OBJECTIVES: We assessed the use of transoral robot-assisted lingual tonsillectomy
      and uvulopalatopharyngoplasty for the surgical management of tongue base
      obstruction in patients with obstructive sleep apnea. METHODS: In a prospective,
      nonrandomized trial using historical controls, patients underwent drug-induced
      sleep endoscopy, transoral robot-assisted lingual tonsillectomy with
      uvulopalatopharyngoplasty, and preoperative and postoperative polysomnography.
      RESULTS: Twenty patients have completed the study to date. The rate of surgical
      success was 45%, and the rate of surgical response was 65%. The mean preoperative
      apnea-hypopnea index of 55.6 decreased by 56.7%, to a mean postoperative value of
      24.1 (p < 0.001), and the minimum arterial oxygen saturation increased from the
      mean preoperative value of 75.8% to the mean postoperative value of 81.7% (p =
      0.013). The mean Epworth Sleepiness Scale score improved from 13.4 to 5.9 (p =
      0.003). One patient had postoperative bleeding that required cauterization,
      resulting in a major complication rate of 4.2%. CONCLUSIONS: Transoral robot
      assisted lingual tonsillectomy with uvulopalatopharyngoplasty is a novel
      technique for the surgical management of obstructive sleep apnea that results in
      a significant decrease in the apnea-hypopnea index, a significant improvement in
      minimum arterial oxygen saturation, and a significant improvement in the Epworth
      Sleepiness Scale score and has an acceptable complication rate.

PMID- 23130538
TI  - Tonsillectomy healing.
AB  - OBJECTIVES: We performed a prospective observation study in an outpatient
      surgical and office setting to compare human post-tonsillectomy healing to human
      cutaneous wound healing and to established animal models of oral healing.
      METHODS: Fourteen teenaged patients underwent planned tonsillectomy. Intraoral
      digital photographs were collected at the time of tonsillectomy, during the
      management of complications, and at postoperative office visits. Serial intraoral
      photographs of one patient were taken at 48-hour intervals from the time of
      surgery until postoperative day 17. RESULTS: Intraoral photographs from the days
      after tonsillectomy revealed a pattern of inflammation and healing that closely
      paralleled that in human skin and in canine and porcine oral wound models.
      CONCLUSIONS: Edema and pain are greatest immediately after surgery, probably as a
      result of thermal effects and expression of inflammatory mediators that stimulate
      pharyngeal nociceptors. Pain gradually decreases over time, with an increase in
      analog pain measures on postoperative days 3 to 5 corresponding to the maximal
      wound inflammation documented in experimental models. Epithelial ingrowth beneath
      a fibrin clot begins shortly after wounding. Separation of the fibrin clot about
      7 days after surgery exposes vascular stroma. Involution of the vascular stroma
      and completion of epithelial coverage correlate with decreased pain levels and a
      lessened risk of bleeding.

PMID- 23130539
TI  - Relationship between the branches of the recurrent laryngeal nerve and the
      inferior thyroid artery.
AB  - OBJECTIVES: The relationship between the recurrent laryngeal nerve (RLN) and the
      inferior thyroid artery (ITA) is an important and helpful landmark for isolating
      the RLN and its branches during surgery. In the present study, we aimed to define
      and classify in detail all of the possible relationships between the two anatomic
      structures and their branches. METHODS: We examined 100 specimens (200 sides)
      from cadavers of 76 men and 24 women who were between 16 and 90 years of age at
      the time of death. After anatomic dissection was performed, the relationship
      between the RLN and the ITA was noted for each side and documented in the form of
      high-resolution photographs. RESULTS: The relationships of both structures and
      their branches were classified into 6 types. Details were verified regarding the
      relationships between the main trunks, between the trunks and branches, and
      between the branches, as follows: type A (ITA trunk to RLN trunk); type B (ITA
      branches to RLN trunk); type C (ITA trunk to RLN branches); type D (ITA branches
      to RLN trunk and RLN branches); type E (ITA branches to RLN branches); and type F
      (others). CONCLUSIONS: Despite the various anatomic and surgical studies already
      performed, in the present study we tried to demonstrate all types of
      relationships between the RLN and the ITA and their branches and devise a new,
      detailed classification of the possible relationships between the two structures.

PMID- 23130540
TI  - Cartilage tympanoplasty in smokers.
AB  - OBJECTIVES: We compared the outcomes of cartilage tympanoplasty in nonsmokers and
      smokers. METHODS: We performed a retrospective chart review of patients who
      underwent cartilage tympanoplasty in a tertiary academic medical center from 1991
      to 2010. There were 129 operations in 118 patients; 84 operations were performed
      in nonsmokers and 45 operations were performed in smokers. The primary outcome
      measure was the tympanic membrane graft take rate at the interval and most recent
      follow-up visits. Secondary measures included recurrence, the need for revision
      surgery, and hearing outcomes. RESULTS: Nonsmokers and smokers had comparable
      long-term rates of intact eardrums (90.6% versus 92.9%; p = 0.99). There was a
      trend toward a higher rate of recurrent or persistent disease requiring further
      operation for smokers (13.3% versus 4.7%; p = 0.09). Both groups had improvement
      in pure tone averages (12.1 dB in nonsmokers and 12.8 dB in smokers) and air-bone
      gaps (9.6 dB in nonsmokers and 5.1 dB in smokers), although the rates were not
      statistically significantly different from each other. The rates of success of
      cartilage tympanoplasty in smokers appear superior to previously published rates
      of noncartilage tympanoplasty. CONCLUSIONS: Cartilage tympanoplasty has success
      rates and postoperative audiological measures that are comparable between smokers
      and nonsmokers. In smokers, cartilage grafting is superior to noncartilage
      grafting and is recommended for any patient who smokes and is undergoing
      tympanoplasty.

PMID- 23130541
TI  - Functional and oncological outcomes of primary versus salvage transoral laser
      microsurgery for supraglottic carcinoma.
AB  - OBJECTIVES: We evaluated the functional and oncological outcomes of transoral
      laser microsurgery (TLM) in patients with previously untreated supraglottic
      carcinoma compared with the outcomes in salvage cases after radiation-based
      treatment. METHODS: We conducted a retrospective case-control study at a single
      academic tertiary care institution. The functional outcomes were stratified by
      prior irradiation and were assessed at baseline, less than 1 week after
      operation, and at last follow-up. RESULTS: Five patients underwent TLM for
      previously untreated disease, and 5 previously irradiated patients underwent
      salvage TLM for local failure. No patient required tracheostomy. There was no
      local recurrence after TLM as primary therapy, and none of those patients
      required radiotherapy. One salvage patient developed local recurrence. The
      duration of feeding tube dependence (p = 0.049) and the rates of chronic
      aspiration (more than 1 month after operation; p = 0.048) were significantly
      higher in the salvage TLM cases than in the previously untreated cases. The
      median scores on the PSS-HN Understandability of Speech were 75 ("usually
      understandable") in the salvage group and 100 ("always understandable") in the
      previously untreated group. CONCLUSIONS: Both local control and function were
      better in the previously untreated patients than in the salvage patients. Our
      findings provide support for the use of TLM as a primary treatment modality for
      selected supraglottic carcinomas, but also suggest a potential for functional
      recovery in both previously untreated and salvage cases.

PMID- 23130542
TI  - Accuracy of tinnitus pitch matching using a web-based protocol.
AB  - OBJECTIVES: We investigated the accuracy of a web-based protocol for tinnitus
      frequency matching compared to that of tinnitus pitch matching performed by an
      audiologist using an audiometer in an anechoic chamber. METHODS: Twenty subjects
      underwent tinnitus frequency-matching in a random order using an audiometer in an
      anechoic chamber and using web-based software with a multiple-choice protocol in
      octave or half-octave steps from 250 Hz to 12,000 Hz and a slider in 25-Hz steps
      from 20 to 20,000 Hz. Octave challenge testing was performed. The participants
      were asked to indicate which protocol resulted in the closest match to their
      tinnitus frequency. RESULTS: The median tinnitus frequency was 6,000 Hz (range,
      2,000 to 12,000 Hz) with use of the audiometer and self-directed multiple-choice
      protocol. With the slider, the median frequency was 5,925 Hz (range, 1,850 to
      16,000 Hz). The patients with a tinnitus frequency higher than 12,000 Hz
      experienced a greater level of satisfaction when using the computer-based slider
      system. Five patients experienced octave confusion with self-directed multiple
      choice tinnitus matching that was corrected accurately after the octave challenge
      step. CONCLUSIONS: A web-based protocol for tinnitus frequency matching is as
      accurate as a standard audiometric protocol. An octave challenge test might be
      necessary for patient-directed tinnitus frequency matching.

PMID- 23130543
TI  - Oral frostbite due to dry ice.
AB  - OBJECTIVES: Dry ice is a commercially available cryogen that is used worldwide.
      It may cause frostbite if misused. However, frostbite of the oral cavity due to
      dry ice has not been previously reported. Here, we describe the first case of dry
      ice-induced frostbite of the oral cavity. METHODS: We present a case of oral
      frostbite due to dry ice and subsequent swelling of the submandibular area and
      lower lip. We discuss the clinical features of oral frostbite due to volatile
      substance abuse. RESULTS: Oral frostbite not only may result in the impairment of
      the affected mucosae directly, but also may adversely affect the tissues in the
      vicinity of the oral cavity floor indirectly. Oral frostbite may cause edema of
      the upper airway tract. In case of severe pharyngolaryngeal edema, either
      tracheal intubation or tracheostomy is necessary. Steroids and antibiotics may be
      effective in preventing the development of pharyngolaryngeal edema. CONCLUSIONS:
      It is important to bear in mind that volatile substance abuse may possibly induce
      unusual events. In particular, special attention should be paid to delayed
      unusual events.

PMID- 23130544
TI  - Efficacy of computed tomographic scans in the evaluation of patients with
      esophageal foreign bodies.
AB  - OBJECTIVES: This study aimed to determine whether computed tomographic (CT) scans
      on which foreign body impaction cannot be detected can be relied upon to decide
      whether a patient requires further investigation by esophagoscopy. This
      information might minimize unnecessary esophagoscopy without incurring the risk
      of a missed impacted foreign body. METHODS: In a retrospective chart review of
      all patients admitted to National University Hospital, Singapore, over the period
      2004 to 2011 for an ingested foreign body, case files of patients who underwent
      preoperative CT scanning followed by esophagoscopy were identified and reviewed.
      The results of the CT scan and the findings of esophagoscopy in these patients
      were analyzed. RESULTS: A total of 376 patients underwent rigid esophagoscopy for
      an ingested foreign body during this period. Of these, 119 patients had CT scans
      performed before the endoscopy. Based on our analysis, the sensitivity of CT
      scanning was 100%, and the specificity was 70.6%. The positive predictive value
      was 89.5%, and the negative predictive value was 100%. None of the patients who
      had CT scans with no detectable foreign body had complications on follow-up.
      CONCLUSIONS: CT scanning appeared to be sensitive and specific in investigation
      of patients with an ingested foreign body. It also has a high negative predictive
      value, which may allow it to be the only preliminary investigation in these
      patients. Based on these data, a prospective study with close monitoring of
      patients who have CT scans with no detectable foreign body can be designed to
      accrue more patients to answer this query.

PMID- 23130545
TI  - Benign paroxysmal positional vertigo associated with Meniere's disease:
      epidemiological, pathophysiologic, clinical, and therapeutic aspects.
AB  - OBJECTIVES: We studied the demographic, pathogenetic, and clinical features of
      benign paroxysmal positional vertigo (BPPV) associated with Meniere's disease.
      METHODS: The medical records of patients with BPPV associated with Meniere's
      disease were reviewed. In all patients, results of a complete otolaryngological,
      audiological, and neurotologic evaluation, including nystagmography, were
      available. Patients with idiopathic BPPV were used as a control group. RESULTS:
      Twenty-nine patients with both disorders were found and were compared with 233
      patients with idiopathic BPPV. The patients with BPPV associated with Meniere's
      disease presented the following features, in which they differed from the
      patients with idiopathic BPPV: 1) a higher percentage of female patients; 2) a
      longer duration of symptoms; 3) common involvement of the horizontal semicircular
      canal; 4) a greater incidence of canal paresis; and 5) more therapeutic sessions
      needed for cure and a higher rate of recurrence. CONCLUSIONS: The BPPV associated
      with Meniere's disease differs from idiopathic BPPV in regard to several
      epidemiological and clinical features, may follow a different course, and
      responds less effectively to treatment.

PMID- 23130546
TI  - Characteristics of vocal fold immobility following endotracheal intubation.
AB  - OBJECTIVES: We investigated the clinical and laryngeal electromyography (LEMG)
      characteristics and the outcome of closed reduction of arytenoid cartilage
      dislocation in patients with vocal fold immobility (VFI) following endotracheal
      intubation. METHODS: Sixty patients with VFI following endotracheal intubation
      were included. Closed reduction was performed under local anesthesia in 54 cases.
      Another 6 patients did not undergo an intervention. Laryngeal behaviors and voice
      function were evaluated. Forty-five patients underwent LEMG testing. RESULTS: All
      patients complained of persistent hoarseness immediately following surgery. The
      LEMG results for 29 of 45 patients showed normal patterns (15 cases) or mildly
      abnormal patterns (14 cases) on the affected side. Sixteen cases displayed
      apparent abnormal LEMG patterns on the affected side. The voices of all 54
      patients improved after reduction. The movement of the affected vocal folds
      recovered to normal in 51 cases. One month after reduction, neuromuscular
      function had improved in 29 of 30 cases.Among the 6 patients who did not undergo
      intervention, 3 had normal or slightly hoarse voices, and 3 experienced moderate
      hoarseness. CONCLUSIONS: Vocal fold immobility following endotracheal intubation
      is typically caused by arytenoid dislocation. Some instances were accompanied by
      an abnormality of the recurrent laryngeal nerve. A timely closed arytenoid
      reduction should be performed to restore patients' normal voices and vocal fold
      mobility. Our reduction technique under local anesthesia can be performed easily
      and obtains satisfactory outcomes within 6 weeks after endotracheal intubation.

PMID- 23130547
TI  - New animal model for assessment of functional laryngeal motor innervation.
AB  - OBJECTIVES: The functional motor innervation of the larynx is not fully
      understood because of the complexity of the peripheral neuroanatomy. Since the
      late 19th century, there has been controversy regarding the role of the superior
      laryngeal nerve, which may have wider motor projections than are currently
      acknowledged. The aim of this study was to develop a large animal model to
      characterize and quantify the functional motor input to the intrinsic laryngeal
      muscles. METHODS: We performed invasive electrophysiology (evoked
      electromyography) in normal pigs. RESULTS: The thyroarytenoid, lateral
      cricoarytenoid, and posterior cricoarytenoid muscles receive dual innervation
      from both the superior and recurrent laryngeal nerves, whereas the cricothyroid
      muscle is innervated only by the superior laryngeal nerve. CONCLUSIONS: The dual
      innervation pattern from both laryngeal nerves supports the concept of a
      laryngeal nerve plexus. The motor input through the external branch of the
      superior laryngeal nerve was surprisingly high. The animal model presented here
      may be used in future investigations of laryngeal reinnervation following nerve
      injury.

PMID- 23130548
TI  - Balloon dilation of the frontal recess: a randomized clinical trial.

PMID- 23130549
TI  - Divergent low water potential response in Arabidopsis thaliana accessions
      Landsberg erecta and Shahdara.
AB  - The Arabidopsis thaliana accession Shahdara (Sha) differs from Landsberg erecta
      (Ler) and other accessions in its responses to drought and low water potential
      including lower levels of proline accumulation. However, Sha maintained greater
      seedling root elongation at low water potential and a higher NADP/NADPH ratio
      than Ler. Profiling of major amino acids and organic acids found that Sha had
      reduced levels of all glutamate family amino acids metabolically related to
      proline, but increased levels of aspartate-derived amino acids (particularly
      isoleucine), leucine and valine at low water potential. Although Sha is known for
      its different abiotic stress response, RNA sequencing and co-expression
      clustering found that Sha differed most from Ler in defence/immune response and
      reactive oxygen-related gene expression. HVA22B and Osmotin34 were two of the
      relatively few abiotic stress-associated genes differentially expressed between
      Ler and Sha. Insensitivity to exogenous glutamine and a different expression
      profile of glutamate receptors were further factors that may underlie the
      differing metabolism and low water potential phenotypes of Sha. These data define
      the unique environmental adaptation and differing metabolism of Sha including
      differences in defence gene expression, and will facilitate further analysis of
      Sha natural variation to understand metabolic regulation and abiotic/biotic
      stress interaction.

PMID- 23130550
TI  - Enhanced performance of dispenser printed MA n-type Bi2Te3 composite
      thermoelectric generators.
AB  - This work presents performance advancements of dispenser printed composite
      thermoelectric materials and devices. Dispenser printed thick films allow for low
      cost and scalable manufacturing of microscale energy harvesting devices. A
      maximum ZT value of 0.31 has been achieved for mechanically alloyed (MA) n-type
      Bi2Te3-epoxy composite films with 1 wt % Se cured at 350  degrees C. The
      enhancement of ZT is a result of increase in the electrical conductivity through
      the addition of Se, which ultimately lowers the sintering temperature (350 
      degrees C). A 62 single-leg thermoelectric generator (TEG) prototype with 5 mm
      *700 MUm * 120 MUm printed element dimensions was fabricated on a custom designed
      polyimide substrate with thick metal contacts. The prototype device produced a
      power output of 25 MUW at 0.23 mA current and 109 mV voltage for a temperature
      difference of 20  degrees C, which is sufficient for low power generation for
      autonomous microsystem applications.

PMID- 23130551
TI  - Retraction: Effects of a pre-visit educational website on information recall and
      needs fulfilment in breast cancer genetic counselling, a randomized controlled
      trial.
AB  - The authors would like to retract their article "Effects of a pre-visit
      educational website on information recall and needs fulfilment in breast cancer
      genetic counselling, a randomized controlled trial" [1]. After publication of
      this paper the co-authors noticed a discrepancy between the analyses as described
      (intention-to-treat analysis) and the analyses as performed (per-protocol
      analysis), leading to an overestimation of the intervention effects. Therefore
      the authors have decided to retract this paper in its current form.

PMID- 23130552
TI  - How does the spacer length of cationic gemini lipids influence the lipoplex
      formation with plasmid DNA? Physicochemical and biochemical characterizations and
      their relevance in gene therapy.
AB  - Lipoplexes formed by the pEGFP-C3 plasmid DNA (pDNA) and lipid mixtures
      containing cationic gemini surfactant of the 1,2-bis(hexadecyl dimethyl ammonium)
      alkanes family referred to as C16CnC16, where n=2, 3, 5, or 12, and the
      zwitterionic helper lipid, 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine
      (DOPE) have been studied from a wide variety of physical, chemical, and
      biological standpoints. The study has been carried out using several experimental
      methods, such as zeta potential, gel electrophoresis, small-angle X-ray
      scattering (SAXS), cryo-TEM, gene transfection, cell viability/cytotoxicity, and
      confocal fluorescence microscopy. As reported recently in a communication (J. Am.
      Chem. Soc. 2011, 133, 18014), the detailed physicochemical and biological studies
      confirm that, in the presence of the studied series lipid mixtures, plasmid DNA
      is compacted with a large number of its associated Na+ counterions. This in turn
      yields a much lower effective negative charge, qpDNA-, a value that has been
      experimentally obtained for each mixed lipid mixture. Consequently, the cationic
      lipid (CL) complexes prepared with pDNA and CL/DOPE mixtures to be used in gene
      transfection require significantly less amount of CL than the one estimated
      assuming a value of qDNA-=-2. This drives to a considerably lower cytotoxicity of
      the gene vector. Depending on the CL molar composition, alpha, of the lipid
      mixture, and the effective charge ratio of the lipoplex, rhoeff, the reported
      SAXS data indicate the presence of two or three structures in the same lipoplex,
      one in the DOPE-rich region, other in the CL-rich region, and another one present
      at any CL composition. Cryo-TEMand SAXS studies with C16CnC16/DOPE-pDNA
      lipoplexes indicate that pDNA is localized between the mixed lipid bilayers of
      lamellar structures within a monolayer of ~2 nm. This is consistent with a highly
      compacted supercoiled pDNA conformation compared with that of linear DNA.
      Transfection studies were carried out with HEK293T, HeLa, CHO, U343, and H460
      cells. The alpha and rhoeff values for each lipid mixture were optimized on
      HEK293T cells for transfection, and using these values, the remaining cells were
      also transfected in absence (-FBS-FBS) and presence (-FBS+FBS) of serum. The
      transfection efficiency was higher with the CLs of shorter gemini spacers (n=2 or
      3). Each formulation expressed GFP on pDNA transfection and confocal fluorescence
      microscopy corroborated the results. C16C2C16/DOPE mixtures were the most
      efficient toward transfection among all the lipid mixtures and, in presence of
      serum, even better than the Lipofectamine2000, a commercial transfecting agent.
      Each lipid combination was safe and did not show any significant levels of
      toxicity. Probably, the presence of two coexisting lamellar structures in
      lipoplexes synergizes the transfection efficiency of the lipid mixtures which are
      plentiful in the lipoplexes formed by CLs with short spacer (n=2, 3) than those
      with the long spacer (n=5, 12).

PMID- 23130553
TI  - Diabetes severely affects attentional performance after coronary artery bypass
      grafting.
AB  - BACKGROUND: Diabetes is a risk factor for (micro) vascular damage of the brain,
      too. Therefore cognitive performance after coronary artery bypass grafting may be
      hypothesized worse in diabetics. To avoid observational errors a reliable tool
      for testing attentional performance was used. We evaluated whether diabetes
      mellitus disposes to distinct cognitive dysfunction after coronary artery bypass
      grafting (CABG). METHODS: Three aspects in attentional performance were
      prospectively tested with three different tests (alertness: composed of un-cued
      and cued reaction, divided attention, and selective attention) by a computerized
      tool one day before and seven days after CABG in a highly selected cohort of 30
      males, 10 of whom had diabetes. Statistical comparisons were done with analysis
      of variance for repeated measurements and Fisher's LSD. RESULTS: Prior to CABG
      there was no statistically meaningful difference between diabetics and non
      diabetics. Postoperatively, diabetic patients performed significantly worse than
      non-diabetics in tests for un-cued (p=0.01) and cued alertness (p=0.03). Test
      performance in divided attention was worse after CABG but independent of diabetes
      status. Selective attention was neither affected by diabetes status nor by CABG
      itself. CONCLUSIONS: Diabetes may have an impact on cognitive performance after
      CABG. More severe deficits in alertness may point to underlying microvascular
      disease.

PMID- 23130562
TI  - Thyroidectomy decreases snoring and sleep apnea: fact or fantasy?

PMID- 23130563
TI  - Further thoughts on the diagnosis and diagnostic criteria for thyroid storm.

PMID- 23130564
TI  - American Thyroid Association guidelines for management of patients with
      anaplastic thyroid cancer.
AB  - BACKGROUND: Anaplastic thyroid cancer (ATC) is a rare but highly lethal form of
      thyroid cancer. Rapid evaluation and establishment of treatment goals are
      imperative for optimum patient management and require a multidisciplinary team
      approach. Here we present guidelines for the management of ATC. The development
      of these guidelines was supported by the American Thyroid Association (ATA),
      which requested the authors, members the ATA Taskforce for ATC, to independently
      develop guidelines for ATC. METHODS: Relevant literature was reviewed, including
      serial PubMed searches supplemented with additional articles. The quality and
      strength of recommendations were adapted from the Clinical Guidelines Committee
      of the American College of Physicians, which in turn was developed by the Grading
      of Recommendations Assessment, Development and Evaluation workshop. RESULTS: The
      guidelines include the diagnosis, initial evaluation, establishment of treatment
      goals, approaches to locoregional disease (surgery, radiotherapy, systemic
      therapy, supportive care during active therapy), approaches to
      advanced/metastatic disease, palliative care options, surveillance and long-term
      monitoring, and ethical issues including end of life. The guidelines include 65
      recommendations. CONCLUSIONS: These are the first comprehensive guidelines for
      ATC and provide recommendations for management of this extremely aggressive
      malignancy. Patients with stage IVA/IVB resectable disease have the best
      prognosis, particularly if a multimodal approach (surgery, radiation, systemic
      therapy) is used, and some stage IVB unresectable patients may respond to
      aggressive therapy. Patients with stage IVC disease should be considered for a
      clinical trial or hospice/palliative care, depending upon their preference.

PMID- 23130568
TI  - Pillar[6]arene/paraquat molecular recognition in water: high binding strength, pH
      responsiveness, and application in controllable self-assembly, controlled
      release, and treatment of paraquat poisoning.
AB  - The complexation between a water-soluble pillar[6]arene (WP6) and paraquat (G1)
      in water was investigated. They could form a stable 1:1 [2]pseudorotaxane with an
      extremely high association constant of (1.02 +/- 0.10) * 10(8) M(-1) mainly
      driven by electrostatic interactions, hydrophobic interactions, and pi-pi
      stacking interactions. This molecular recognition has not only high binding
      strength but also pH-responsiveness. The threading and dethreading processes of
      this [2]pseudorotaxane could be reversibly controlled by changing the solution
      pH. This novel recognition motif was further used to control the aggregation of a
      complex between WP6 and an amphiphilic paraquat derivative (G2) in water. The
      reversible transformations between micelles based on G2 and vesicles based on
      WP6?G2 were realized by adjusting the solution pH due to the pH-responsiveness of
      WP6. The controlled release of water-soluble dye molecules from the vesicles
      could be achieved by the collapse of the vesicles into the micelles upon changing
      the solution pH to acidity. Additionally, the high binding affinity between WP6
      and paraquat could be utilized to efficiently reduce the toxicity of paraquat.
      After the formation of a stable host-guest complex between WP6 and paraquat, less
      opportunity was available for paraquat to interact with the reducing agents in
      the cell, which made the generation of its radical cation more difficult,
      resulting in the efficient reduction of paraquat toxicity.

PMID- 23130567
TI  - Expression of geminiviral AC2 RNA silencing suppressor changes sugar and
      jasmonate responsive gene expression in transgenic tobacco plants.
AB  - BACKGROUND: RNA-silencing is a conserved gene regulation and surveillance
      machinery, which in plants, is also used as major defence mechanism against
      viruses. Various virus-specific dsRNA structures are recognized by the silencing
      machinery leading to degradation of the viral RNAs or, as in case of
      begomoviruses, to methylation of their DNA genomes. Viruses produce specific RNA
      silencing suppressor (RSS) proteins to prevent these host defence mechanisms, and
      as these interfere with the silencing machinery they also disturb the endogenous
      silencing reactions. In this paper, we describe how expression of AC2 RSS,
      derived from African cassava mosaic geminivirus changes transcription profile in
      tobacco (Nicotiana tabacum) leaves and in flowers. RESULTS: Expression of AC2 RSS
      in transgenic tobacco plants induced clear phenotypic changes both in leaves and
      in flowers. Transcriptomes of these plants were strongly altered, with total of
      1118 and 251 differentially expressed genes in leaves and flowers, respectively.
      The three most up-regulated transcript groups were related to stress, cell wall
      modifications and signalling, whereas the three most down-regulated groups were
      related to translation, photosynthesis and transcription. It appears that many of
      the gene expression alterations appeared to be related to enhanced biosynthesis
      of jasmonate and ethylene, and consequent enhancement of the genes and pathways
      that are regulated by these hormones, or to the retrograde signalling caused by
      the reduced photosynthetic activity and sugar metabolism. Comparison of these
      results to a previous transcriptional profiling of HC-Pro RSS-expressing plants
      revealed that some of same genes were induced by both RSSs, but their expression
      levels were typically higher in AC2 than in HC-Pro RSS expressing plants. All in
      all, a large number of transcript alterations were found to be specific to each
      of the RSS expressing transgenic plants. CONCLUSIONS: AC2 RSS in transgenic
      tobacco plants interferes with the silencing machinery. It causes stress and
      defence reactions for instance via induction of the jasmonate and ethylene
      biosynthesis, and by consequent gene expression alteration regulated by these
      hormones. The changed sugar metabolism may cause significant down-regulation of
      genes encoding ribosomal proteins, thus reducing the general translation level.

PMID- 23130569
TI  - Isolated intrauterine growth restriction: a survey of Central Association of
      Obstetricians Gynecologists (CAOG) members.
AB  - OBJECTIVE: The objective was to ascertain clinicians' opinions and current
      management with isolated (no concomitant morbidity) intrauterine growth
      restriction (IUGR). METHODS: Members of the Central Association of Obstetricians
      and Gynecologists (CAOG) were surveyed. We considered consensus to be agreement
      among 90% of the respondents. RESULTS: The response rate was 36% (137/385). Among
      the 21 questions on the topic, the only consensus was that none of the
      respondents informed women of the recurrence rate of IUGR. There was variance in
      what constitutes IUGR as well as practice patterns for detection and management
      of suboptimal growth. Ten (7%) of the respondents had at least one litigation
      involving management of IUGR. Responses from 87 general obstetrician
      gynecologists varied significantly from that of 33 maternal-fetal medicine (MFM)
      subspecialists for 48% (10/21) of the survey questions (p < 0.05). CONCLUSIONS:
      There is large practice variation in detection and management of isolated IUGR.
      This stresses the need for additional studies and a national guideline on its
      management.

PMID- 23130570
TI  - Extraordinary photocurrent harvesting at type-II heterojunction interfaces:
      toward high detectivity carbon nanotube infrared detectors.
AB  - Despite the potentials and the efforts put in the development of uncooled carbon
      nanotube infrared detectors during the past two decades, their figure-of-merit
      detectivity remains orders of magnitude lower than that of conventional
      semiconductor counterparts due to the lack of efficient exciton dissociation
      schemes. In this paper, we report an extraordinary photocurrent harvesting
      configuration at a semiconducting single-walled carbon nanotube (s-SWCNT)/polymer
      type-II heterojunction interface, which provides highly efficient exciton
      dissociation through the intrinsic energy offset by designing the s-SWCNT/polymer
      interface band alignment. This results in significantly enhanced near-infrared
      detectivity of 2.3 * 10(8) cm.Hz(1/2)/W, comparable to that of the many
      conventional uncooled infrared detectors. With further optimization, the s
      SWCNT/polymer nanohybrid uncooled infrared detectors could be highly competitive
      for practical applications.

PMID- 23130571
TI  - Factors associated with reproductive health care utilization among Ghanaian
      women.
AB  - BACKGROUND: This study investigates factors determining the timing of antenatal
      care (ANC) visit and the type of delivery assistant present during delivery among
      a national representative sample of Ghanaian women. METHOD: Data for the study
      was drawn from the women questionnaire (N=4,916) of the 2008 Ghana Demographic
      and Health Survey among 15-49-years-old women. Multivariate logistic regression
      analysis was used to explore factors determining the type of delivery assistance
      and timing of ANC visit for live births within five years prior to the survey.
      RESULTS: Majority of Ghanaian women attended ANC visit (96.5%) but many (42.7%)
      did so late (after the first trimester), while 36.5% had delivery without the
      assistance of a trained personnel (30.6%) or anyone (5.9%). Age (OR=1.5, CI=1.1
      1.9, OR for 25-34-year-olds compared to 15-24-year-olds), religion (OR=1.8,
      CI=1.2-2.8, OR for Christians versus Traditional believers) wealth index (OR=2.6,
      CI=1.7-3.8, OR for the richest compared to the poorest) were independently
      associated with early ANC visit. Likewise, age, place of residence, education and
      partner's education were associated with having a delivery assisted by a trained
      assistant. Also, Christians (OR=1.8, CI=1.1-3.0) and Moslems (OR=1.9, CI=1.1-3.3)
      were more likely to have trained delivery assistants compared to their
      counterparts who practised traditional belief. Furthermore, the richer a woman
      the more likely that she would have delivery assisted by a trained personnel
      (OR=8.2, CI= 4.2-16.0, OR for the richest in comparison to the poorest).
      CONCLUSIONS: Despite the relatively high antenatal care utilisation among
      Ghanaian women, significant variations exist across the socio-demographic
      spectrum. Furthermore, a large number of women failed to meet the WHO
      recommendation to attend antenatal care within the first trimester of pregnancy.
      These findings have important implications for reducing maternal mortality ratio
      by three-quarters by the year 2015.

PMID- 23130572
TI  - Uncertainties monitoring groundwater levels in exploratory wells.

PMID- 23130573
TI  - Feed enzyme supplementation does not ameliorate Foot Pad Dermatitis in broiler
      chickens fed on a corn-soyabean diet.
AB  - 1. Foot Pad Dermatitis (FPD) can be a serious health, quality and welfare problem
      in poultry production, with a significant affect on the economics of production.
      The physico-chemical properties of (NSP) have been correlated with increases in
      excreta viscosity and adherence, and hence FPD in broiler chickens. 2. Two
      broiler experiments were conducted to evaluate the effects of different dietary
      non-starch polisaccharide (NSP) applications to corn-soyabean based diets in
      replicated floor pens. In addition to live performance, the incidence and
      severity of FPD was scored and, in experiment 2, intestinal viscosity and ammonia
      volatilization were measured. 3. Live performance did not vary with the different
      treatments in either experiment and the incidence and severity of FPD, and
      ammionia volatisation in experiment 2, were unaffected. However, birds reared on
      enzyme supplemented diets had lower (P < 0.001) intestinal viscosity levels in
      experiment 1. 4. In this study with corn-soyabean meal based diets, dietary
      enzyme supplementation had no affect on the incidence and severity of FPD. The
      lack of an association between the excreta viscosity and FPD is attributed to the
      multifactorial etiology of this condition.

PMID- 23130574
TI  - Corticosterone, cortisol, triglycerides, aspartate aminotransferase and uric acid
      plasma concentrations during foie gras production in male mule ducks (Anas
      platyrhynchos * Cairina moschata).
AB  - 1. Corticosterone, cortisol, triglycerides, aspartate aminotransferase (AST) and
      uric acid (UA) plasma concentration were measured at 8 (7 days after group
      housing), 12 (after 7 days of force feeding) and 13 weeks of age (at slaughter
      after 12 days of force feeding), and 45 min after an adrenocorticotrophic hormone
      (ACTH) stimulation test at 8 weeks of age in 12 male mule ducks in an on-farm
      experiment.   2. No significant increase of corticosterone was found during the
      force-feeding period compared with the concentration after housing.   3.
      Comparison of corticosterone and cortisol values indicates that cortisol can be
      considered as a reliable acute stress indicator in future routine examinations.  
      4. Plasma concentrations of triglycerides and aspartate aminotransferase
      increased progressively from pre-force feeding period to slaughtering.   5.
      Plasma concentrations of uric acid increased from the start at 8 weeks of age to
      the mid-force feeding period but no difference was noticed between the mid-force
      feeding period and slaughtering.   6. It is concluded that acute stress induced
      by force-feeding is similar at the beginning and end of the commercial production
      of foie gras.

PMID- 23130575
TI  - Influence of crate height during slaughter transport on the welfare of male
      turkeys.
AB  - 1. Poultry are usually transported in crates which provide the birds with very
      limited space. Slaughter transport of male turkeys is often carried out using
      crates that are 40 cm or less in height where it is not possible for them to
      stand up. There is little information on how this physical restriction over many
      hours affects the birds.   2. The aim of the study was to compare the welfare of
      male turkeys transported in crates 40 cm and 55 cm in height. Observations on the
      birds' behaviour during lairage, carcass damage and meat quality were carried out
      after four commercial slaughter transport journeys.   3. Birds in 40 cm crates
      panted more and lay down more than birds in 55 cm crates during lairage. A large
      percentage of the carcasses had some damage. Significantly more birds from the 55
      cm crates had scratches on their backs than birds from the 40 cm crates. There
      was no significant difference in meat quality between birds transported in the
      two crate heights.   4. Both positive and negative effects of increased crate
      height were established and there is no evidence from this study that merely
      increasing crate height improves turkey welfare. Other solutions should therefore
      be sought in order to improve the welfare of birds during transport.

PMID- 23130576
TI  - Backyard chicken keeping in the Greater London Urban Area: welfare status,
      biosecurity and disease control issues.
AB  - 1. The aim of the study was to collect baseline data on welfare, biosecurity and
      diseases of backyard chickens kept in the Greater London Urban Area (GLUA),
      United Kingdom (UK).   2. A total of 65 backyard chicken flock-keepers were
      recruited from May to July 2010 through adverts on websites, at City farms,
      veterinary practices and pet feed stores and surveyed by means of a
      questionnaire. A total of 30 responses were suitable for analysis.   3.
      Information on keepers' and flocks' characteristics, housing and husbandry
      practices and owners' knowledge of health problems in chickens and zoonotic
      diseases was collected. A welfare assessment protocol was developed and the
      flocks assessed accordingly.   4. Results showed that chickens were generally
      provided with living conditions that allowed them to perform their natural
      behaviours.   5. Most of the flock owners did not comply with the regulations of
      the Department for Environment, Food and Rural Affairs (Defra) on the feeding of
      catering waste.   6. Disease prevention measures such as vaccination and
      biosecurity, including limiting the access of human visitors, wild birds and
      rodents to the flocks were rare.   7. A lack of avian and zoonotic disease
      knowledge and awareness among the owners has implications for disease control and
      highlights the need for improved communication between owners, authorities and
      veterinarians.

PMID- 23130577
TI  - Effects of fish oil and conjugated linoleic acids on carnitine homeostasis in
      laying hens.
AB  - 1. The effects of n-3 polyunsaturated fatty acids (PUFA) and conjugated linoleic
      acids (CLA) on genes involved in carnitine homeostasis were compared in laying
      hens. Three groups of laying hens were fed on a control diet or a diet with
      either 3% of fish oil or CLA for 4 weeks.   2. Feed intake and egg production
      rate did not differ between the three groups. Diets with fish oil or CLA had only
      a weak effect on mRNA levels of PPARalpha target genes (ACO, CPT-I) in the liver
      and did not influence mRNA concentrations of the most important carnitine
      transporter OCTN2, enzymes of involved in carnitine synthesis (TMLD, TMABA-DH,
      BBD) or concentrations of carnitine in plasma, liver and total egg contents.   3.
      Hens fed the CLA diet had lower concentrations of free and total carnitine in egg
      yolk but higher concentrations of carnitine in albumen than control hens (P <
      0.05), whereas the amount of free and total carnitine in whole egg did not
      differ.   4. In conclusion, the study showed that feeding fish oil or CLA causes
      only a weak activation of PPARalpha in tissues of laying hens that probably
      explained the lack of effect on carnitine homeostasis. The results contrast with
      those in humans and mice that show a significant effect of synthetic PPARalpha
      agonists on carnitine homeostasis in humans and mice.

PMID- 23130578
TI  - Effects of contact dermatitis on hepatic gene expression in broilers.
AB  - 1. Severe foot and hock dermatitis in broiler chickens can reduce growth rate and
      increase susceptibility to bacterial infection, affecting both profitability and
      welfare. However, little is known about the underlying physiological changes
      associated with foot and hock lesions. 2. This study compared global hepatic gene
      expression in control birds and those with ammonia-induced foot and hock lesions
      using Agilent 44 K chicken oligonucleotide microarrays (8 birds per group). 3. In
      total, 417 genes were differentially expressed of which 174 could be mapped onto
      the genome. Genes associated with energy metabolism, thyroid hormone activity and
      cellular control were affected, while there was also evidence of an up-regulation
      of genes linked to a pro-inflammatory response. 4. It is conceivable that pain is
      the underlying cause for the observed changes in energy metabolism genes. 5.
      Changes in hepatic gene expression provide new information on how a chicken's
      physiological mechanisms alter to cope with foot and hock lesions. The findings
      support other data indicating that birds with increased severity of lesions are
      likely to be in pain and that growth will be compromised. Reduction of the
      incidence of dermatitis by improved husbandry should therefore benefit both
      welfare and commercial performance.

PMID- 23130579
TI  - Polymorphisms of the PNPLA3 gene and their associations with chicken growth and
      carcass traits.
AB  - 1. An F(2) resource population of Gushi chickens crossed with Anka broilers was
      used to investigate the genetic effects of the chicken PNPLA3 gene on growth and
      adipose accumulation.   2. Associations between three SNPs (g.40006G > T,
      g.42344T > C and g.42404A > T) and broiler traits were determined using linkage
      disequilibrium, haplotype construction and association analysis.   3. The
      g.40006G > T mutation was associated with body weights at 4, 6, 8, 10 and 12
      weeks of age, carcass weight, evisceration weight and semi-evisceration weight (P
      < 0.05).   4. Haplotypes of the g.42344T > C and g.42404A > T mutations were
      associated with body weight at 12 weeks, carcass weight, evisceration weight, and
      semi-evisceration weight (P < 0.05) and were associated with significant
      dominance effects.   5. The results suggest that the PNPLA3 gene may be in
      linkage with the causative mutation or a QTL controlling growth traits in
      chickens. In contrast to human studies, the polymorphisms were not associated
      with fat related traits.

PMID- 23130580
TI  - Characterisation of tetra-nucleotide microsatellite loci in the ostrich (Struthio
      camelus).
AB  - 1. Eleven polymorphic tetra-nucleotide microsatellite loci were identified in the
      ostrich (Struthio camelus) using a selective enrichment protocol.   2. The
      average number of alleles observed was 6.6 with an average heterozygosity of 0.4.
      3. The population was found to be in Hardy-Weinberg equilibrium and two of the
      loci had a greater than 95% probability of having null alleles.   4. These
      microsatellite loci will add to the existing pool of markers available for the
      ostrich and help to facilitate analysis of population structure and pedigree
      determination.

PMID- 23130581
TI  - Virulence-associated genes in avian pathogenic Escherichia coli from laying hens
      in Apulia, Southern Italy.
AB  - 1. Escherichia coli isolated from lesions (Avian Pathogenic E. coli - APEC) of
      layer hens affected by colibacillosis and from intestinal contents of clinically
      healthy birds (Avian Faecal E. coli - AFEC) were serotyped. All the isolates were
      investigated for the presence of virulence genes to determine which genes were
      more closely related to those from lesions.   2. A number of different serogroups
      were detected, O78 being predominant among the isolates from colibacillosis.   3.
      E. coli isolated from lesions were not linked to a specific pathotype (set of
      common virulence genes).   4. The presence of the virulence genes, with the
      exception of astA, was associated more generally with APEC strains.   5.
      Statistically, genes such as cva/cvi, tsh, iss, irp2 and iucD were more related
      to isolates from colibacillosis.   6. It is suggested that the detection of these
      genes in a rapid and inexpensive test for field practitioners could provide
      useful information about the potential virulence of E. coli isolated in
      commercial layer flocks.

PMID- 23130582
TI  - Effects of dietary glutamine and gamma-aminobutyric acid on meat colour, pH,
      composition, and water-holding characteristic in broilers under cyclic heat
      stress.
AB  - 1. An experiment was conducted to evaluate the effects of dietary glutamine (Gln,
      0 and 5 g/kg) and gamma-aminobutyric acid (GABA, 0 and 100 mg/kg) on raw breast
      meat colour, pH, composition and water-holding characteristic of broilers under
      cyclic heat stress (HS).   2. A total of 360 21-d-old Arbor Acres male chicks
      were randomly assigned to 5 treatment groups (6 replicates of 12 birds per cage).
      The positive control (PC) broilers were kept in a thermoneutral chamber (22-24
      degrees C) and fed on the basal diet. The other 4 groups were kept in a cyclic HS
      chamber (30-34 degrees C) for 9 h (from 09:00 to 18:00).   3. A significant
      increase was observed in breast meat lightness at 28, 35 and 42 d; and pH values
      at 28, 35 and 42 d; while a significant decrease was observed in breast meat
      cooking loss (CL) and contents of moisture, crude protein (CP), crude fat (CF)
      and crude ash (CA) due to HS.   4. The supplementation with 0.5 g Gln/kg
      decreased lightness at 28, 35 and 42 d; while increasing redness at 28 d,
      yellowness at 35 d, contents of CP, CF and CA, thawing loss (TL) and drip loss
      (DL). The addition of 100 mg GABA/kg decreased lightness at 28 and 35 d, pH value
      at 28, 35 and 42 d, and TL; while increasing redness at 28 d, 35 and 42 d,
      contents of moisture, CP and CF.   5. The lightness, redness, and pH value;
      contents of moisture, CP, CF and CA; and TL, DL and CL of breast meat of broilers
      fed with the mixture of Gln and GABA under cyclic HS were similar to those of the
      broilers in the PC group.   6. Significant interactions were found between Gln
      and GABA for yellowness at 28 and 35 d; pH at 28, 35 and 42 d; moisture content,
      CP content, water-holding capacity and TL.   7. These results demonstrated that
      dietary Gln and GABA offer a potential nutritional strategy to prevent cyclic HS
      related depression in broiler meat chemical composition and quality.

PMID- 23130583
TI  - A multi-microbe probiotic formulation processed at low and high drying
      temperatures: effects on growth performance, nutrient retention and caecal
      microbiology of broilers.
AB  - 1. Two experiments were conducted to evaluate a multi-microbe probiotic
      formulation processed at low (LT) or high (HT) drying temperature.   2. In both
      the experiments, 640 d-old Ross male chicks were randomly allotted to 4
      treatments on the basis of initial BW for 35 d experiments.   3. In experiment
      one, dietary treatments were a negative control (NC; basal diet without any
      antimicrobial); positive control (PC; basal diet +10 mg/kg avilamycin); basal
      diet with 0.3% probiotic LT; and basal diet with 0.3% probiotic HT.   4. Improved
      overall weight gain, FCR and retention of CP were observed in birds fed the PC
      and probiotic diets when compared with birds fed the NC diet. At d 21, birds fed
      the probiotic and NC diets had more caecal Bifidobacterium and total anaerobes
      than birds fed the PC diet; while birds fed the PC and probiotic diets had fewer
      caecal Clostridium than birds fed the NC diet at d 35.   5. In experiment two, a
      2 * 2 factorial arrangement of treatments was employed to evaluate the effects of
      two concentrations of probiotic HT (0.30 or 0.60%) and avilamycin (0 or 10
      mg/kg).   6. Birds fed the 0.60% probiotic HT diet showed improved overall weight
      gain and CP retention, higher Lactobacillus and Bifidobacterium in the caecum,
      and reduced Clostridium and coliforms in the caecum. Inclusion of avilamycin
      improved the overall weight gain and feed intake, and reduced the caecal
      Clostridium and Bifidobacterium population.   7. In conclusion, high drying
      temperature had no effect on the efficacy of the multi-microbe probiotic
      formulation; while the probiotic HT formulation was more effective at the 0.60%
      level. Moreover, inclusion of avilamycin improved performance of birds but did
      not have any interaction with probiotics.

PMID- 23130584
TI  - Evaluating the impact of excess dietary tryptophan on laying performance and
      immune function of laying hens reared under hot and humid summer conditions.
AB  - 1. Tryptophan (Trp), besides its role as an essential amino acid in protein
      synthesis, may also have other important effects on laying hens under summer
      conditions.   2. Babcock Brown layers (n = 768), 40 weeks of age, were allocated
      to 4 treatment groups, each of which included 6 replicates of 32 hens. Each group
      received the same basal diet, formulated with maize and soybean meal, for 8
      weeks. Hens were fed on the basal diet with 0.0, 0.2, 0.4, and 0.8 g/kg L-Trp to
      achieve dietary concentrations of 1.7, 1.9 g/kg, 2.1 g/kg or 2.5 g/kg of Trp,
      respectively.   3. Supplementing L-Trp had no affect on laying performance.
      Adding 0.2 or 0.4 g/kg L-Trp improved egg shell strength compared with those fed
      on the control diet. Serum albumin concentration increased at 0.4 g/kg compared
      with those receiving 0.0 or 0.8 g/kg Trp. The addition of Trp at 0.4 g/kg
      increased serum IgM concentration quadratically. Serum superoxide dismutase (T
      SOD) increased linearly and quadratically at 0.4 g/kg.   4. In conclusion, we
      suggest that 0.2 to 0.4 g/kg Trp may have beneficial effects on laying hens under
      conditions of high temperature and humidity.

PMID- 23130585
TI  - The effect of glycerol on mRNA expression of growth hormone, insulin-like growth
      factor, and mitochondrial breast muscle genes of Japanese quail.
AB  - 1. A study was carried out to evaluate the expression of growth hormone (GH),
      insulin-like growth factor I (IGF-I), mitochondrial adenine nucleotide
      translocase (ANT), cytochrome oxidase III (COX III) and avian uncoupling protein
      (avUCP) genes in 14-d-old Japanese quail that were fed different levels of
      glycerol (0%, 4%, and 12% dietary glycerol) which replaced maize as an energy
      source.   2. Total RNA was extracted from the breast muscle, and cDNA was
      amplified using real-time PCR with primers specific to the examined genes.   3.
      Quail fed the diet with 12% glycerol supplementation presented higher growth
      hormone (GH) mRNA expression than did those fed 0% glycerol. Supplementation with
      12% glycerol negatively influenced IGF-I mRNA expression and reduced ANT mRNA
      expression in comparison with the treatment with no glycerol. COX III mRNA
      expression in the pectoralis superficialis muscle was decreased by 26% in quail
      fed 12% glycerol compared with those fed 0 and 4% glycerol.   4. There was no
      difference in UCP mRNA expression between quail fed 0 and 4% glycerol; however,
      UCP expression was reduced (73%) in birds fed the 12% glycerol diet compared with
      the level in those fed the 4% glycerol diet.   5. The inclusion of 4% glycerol in
      the diet produced results similar to those of the diet with no glycerol. Based on
      quail performance and the expression of the GH, IGF-I, ANT, COX III and UCP
      genes, 4% glycerol can be used in quail feeding without any harmful effects.

PMID- 23130586
TI  - Effect of supplementation of the laying hen diet with olive leaves (Olea europea
      L.) on lipid oxidation and fatty acid profile of alpha-linolenic acid enriched
      eggs during storage.
AB  - 1. The aim of this study was to evaluate the effect of supplementation of the
      layer diet with olive leaves (Olea europea L.) on lipid oxidation and fatty acid
      profile of alpha-linolenic acid enriched eggs during refrigerated storage, and to
      compare this effect with alpha-tocopheryl acetate supplementation.   2. A total
      of 72 brown Lohmann laying hens, equally allocated to 3 groups, were fed on diets
      supplemented with 40 g/kg linseed oil, or linseed oil and olive leaves at 10 g/kg
      or linseed oil and alpha-tocopheryl acetate at 200 mg/kg. Collected eggs were
      analysed for fatty acid profile and lipid oxidation either fresh or following 60
      d storage at 4 degrees C.   3. Results showed that olive leaves or alpha
      tocopheryl acetate supplementation reduced lipid hydroperoxide concentration in
      fresh eggs but had no effect on their fatty acid profile and malondialdehyde
      (MDA) content compared to controls.   4. Refrigerated storage for 60 d decreased
      the proportions of PUFAs but increased those of MUFAs in eggs from the control
      diet, whilst it had no effect on the fatty acid composition of eggs from the
      diets supplemented with olive leaves or alpha-tocopheryl acetate, which in turn
      showed decreased concentrations of lipid hydroperoxides and MDA.

PMID- 23130587
TI  - Changes in plasma gonadotrophins, 17beta-oestradiol, progesterone, prolactin,
      thyroxine and triiodothyronine concentrations in female Japanese quail (Coturnix
      coturnix japonica) of a heavy body weight line during photo-induced ovarian
      growth and regression.
AB  - 1. Simultaneous changes of the width of the cloacal opening and plasma
      luteinising hormone (LH), follicle stimulating hormone (FSH), 17beta-oestradiol,
      progesterone, prolactin, thyroxine (T(4)) and triiodothyronine (T(3)) during
      photo-induced ovarian growth and regression were measured in commercially bred
      Japanese quail from a heavy body weight line.   2. Somatically mature female
      Japanese quail were transferred from short days (light:dark 8L:16D) at 10 degrees
      C to long days (16L:8D) at 20 degrees C, and sexually mature female Japanese
      quail were transferred from long to short days. All variables were measured at
      transfer and every five days thereafter (except for a measurement at 12 instead
      of 10 d) for 35 d.   3. Transfer from short to long days caused significant
      increases in LH, FSH, 17beta-oestradiol, ovary weights and oviduct weights after
      five days, and in the cloacal opening after 12 d. T(3) decreased after five days,
      whereas no significant changes were observed in T(4) concentrations. Progesterone
      and prolactin both decreased after 25 long days.   4. The transfer of quail from
      long to short days caused significant decreases in LH, FSH, 17beta-oestradiol,
      progesterone, prolactin, ovary and oviduct weights after 12 d and an increase in
      T(3). There was no significant change in T(4) concentrations. The cloacal opening
      decreased after 25 short days.   5. These results are the first to show
      simultaneous changes in gonadotrophins, sex steroids, thyroid hormones and
      prolactin during photo-induced gonadal growth and regression in female Japanese
      quail.

PMID- 23130588
TI  - Changes in body temperature during growth and in response to fasting in growing
      modern meat type chickens.
AB  - 1. Rectal or core body temperature was determined in a study to examine the
      effects of fasting in modern meat type broilers at three stages of growth, namely
      d 19, 33 and 47.   2. There were two treatment groups: fed with feed available ad
      libitum and fasted. Rectal temperatures were determined at noon (1200 h). At that
      time, feed was removed from the fasted group. The body temperatures were then
      determined again after 6, 12, 18 and 24 h.   3. Core body temperatures decreased
      with fasting. The decrease was evident after as little as 6 h of fasting with a
      further decline evident by 12 h.   4. Accompanying the decrease in body
      temperature with fasting there were decreases in the venous concentrations of
      carbon dioxide in the blood and sodium in the plasma.   5. The decrease in both
      body temperature and carbon dioxide presumably reflects depressed metabolic rate.
      6. Unexpectedly, the core body temperature increased progressively with age in
      the control fed group (d 19 = 41.04 +/- 0.02 degrees C, d 33 = 41.65 +/- 0.05
      degrees C, d 47 = 42.21 +/- 0.12 degrees C).   7. In the fed control group, core
      body temperatures were reduced at night, when feeding activity would be
      anticipated to be greatly reduced.

PMID- 23130589
TI  - Early-age cold conditioning of broilers: effects of timing and temperature.
AB  - 1. The aim of the present study was to determine the effects of early-age cold
      conditioning (CC) on performance, ascites mortality, thyroid hormones status and
      immune response (leucocytes count) of broiler chickens.   2. A total of 336
      chicks at 2 and 3 d of age were exposed to 20 or 25 degrees C (for 3 or 6 h) in a
      2 * 2 * 2 factorial experiment, while a control group was kept under normal
      temperature conditions (30 degrees C). Thereafter, both control and cold
      conditioned birds were reared under standard conditions until 42 d of age.   3.
      The results showed that performance (weight gain and feed efficiency) was
      improved by CC at the end of the rearing period. Carcase traits (breast, thigh
      and abdominal fat percentage) were not affected by different treatments. Heart
      weight was lower in cold conditioned birds accompanied with lower ascites
      mortality. Total leucocyte count was higher in CC birds. Higher concentrations of
      thyroxin (T(4)) were found in plasma of treated groups, while triiodothyronine
      (T(3)) to T(4) ratio was decreased.   4. In conclusion, it seems that early age
      CC improves performance and reduces ascites mortality of broilers through altered
      thyroid hormones metabolism and leucocyte function. According to the results, the
      best timing for CC of broilers was 20 degrees C for 6 h at the age of 2 d, and no
      significant benefit was observed by repeated CC.

PMID- 23130590
TI  - Effects of lycopene on in vitro quality and lipid peroxidation in refrigerated
      and cryopreserved turkey spermatozoa.
AB  - 1. The effects of lycopene-enriched extenders on the in vitro quality of turkey
      semen including lipid peroxidation were examined after chilled and frozen
      storage.   2. Five pools of semen diluted in extenders containing 0, 0.05 or 0.1
      mg/ml of lycopene were stored at 5 degrees C for 48 h or cryopreserved as pellets
      and the following variables determined in fresh samples and samples stored
      chilled or frozen: sperm motility, viability, osmotic resistance, DNA integrity
      and lipid peroxidation (as malonaldehyde production).   3. Semen quality was
      generally compromised after storage, especially post-freezing. However, in the
      presence of the highest dose of lycopene, both the viability and osmotic
      resistance of chilled spermatozoa and the DNA integrity of frozen spermatozoa
      were similar to those of fresh spermatozoa.   4. Greater lipid peroxidation was
      detected in refrigerated compared to fresh or cryopreserved spermatozoa. However,
      spermatozoa chilled in lycopene-enriched extenders showed significantly lower
      malonaldehyde levels than those chilled without lycopene, while the addition of
      lycopene to the freezing medium served to maintain the lipid peroxidation levels
      observed in fresh semen.   5. In conclusion, the presence of lycopene in the
      extender improved the survival of turkey spermatozoa after liquid-storage and
      protected DNA integrity against cryodamage. The beneficial effects of lycopene
      observed could be related to its capacity to diminish sperm lipid peroxidation
      during refrigeration or cryopreservation.

PMID- 23130591
TI  - Silent cerebral embolism and new technologies for catheter ablation of atrial
      fibrillation: time to take a deep breath.

PMID- 23130592
TI  - Does diffusion-weighted MRI (DW-MRI) change treatment strategy in pediatric
      cholesteatoma?
AB  - CONCLUSION: This review highlights the currently limited and contradictory
      evidence on the role of diffusion-weighted magnetic resonance imaging (DW-MRI) in
      the management of pediatric cholesteatoma patients. Available data confirm the
      need for prospective DW-MRI studies of a larger number of pediatric patients.
      Factors such as patient compliance, adhesion to follow-up or local logistic
      circumstances should also be considered. OBJECTIVES: This systematic review aimed
      to collect and analyze the body of evidence on the usefulness of DW-MRI in first
      stage tympanoplasty and in replacing second-look surgery in children with
      cholesteatoma. METHODS: A comprehensive search of medical databases was
      conducted. The keywords used were pediatric/paediatric, magnetic resonance
      imaging, MRI, DW-MRI, cholesteatoma, child, and all meaningful combinations of
      them. RESULTS: Only one study with 17 patients primarily fulfilled all criteria.
      Sensitivity, specificity, and positive and negative predictive values were 62%,
      88%, 89%, and 58%, respectively. A second study retrospectively analyzed a subset
      of younger patients (n = 21) of a larger population. Sensitivity, specificity,
      and positive and negative predictive values were 100%. One additional study
      described 1 child and 11 adolescents among 32 cases. In all cases the correlation
      between imaging and surgery findings was 100%. There were no randomized
      controlled trials and power calculations were not performed.

PMID- 23130596
TI  - They're baaaack!

PMID- 23130593
TI  - Single indication of labor induction with prostaglandins: is advanced maternal
      age a risk factor for cesarean section? A matched retrospective cohort study.
AB  - OBJECTIVE: The aim of this study is to investigate if advance maternal age is an
      independent risk factor for cesarean section in women induced with
      prostaglandins. Only patients with a single indication for induction of labor
      were considered. METHODS: A matched retrospective cohort study was conducted. A
      study group of 112 women aged 35 or older was enrolled. The control group
      included 216 women aged 34 or younger. Multivariate logistical regression models
      were fitted for the prediction of the cesarean section. RESULTS: There were no
      statistically significant differences in characteristics of the patients in the
      study and control groups. However, a higher prevalence of nulliparous women was
      found in control group (p = 0.002). The indications of labor induction were
      homogeneous in the two groups. No significant differences were found in the route
      of delivery. The median time of labor was significantly shorter in the study
      group (p = 0.002), and the birth weight and the placental weight were
      significantly lower in the study group. Advanced maternal age and newborn weight
      were directly related, whereas time of labor, Bishop score and parity were
      inversely related to a higher cesarean rate. CONCLUSIONS: When single indication
      of induction of labor with prostaglandins is considered, advanced maternal age
      represents a significant independent risk factor for cesarean delivery.

PMID- 23130597
TI  - Assessment of occlusion curriculum in predoctoral dental education: report from
      ACP Task Force on Occlusion Education.
AB  - PURPOSE: The purposes of this report were to (1) assess the current occlusion
      curriculum in the predoctoral prosthodontic education of US dental institutions
      and (2) to examine the opinions of faculty, course directors, and program
      directors on the contents of occlusion curriculum. MATERIALS AND METHODS: The
      Task Force on Occlusion Education from the American College of Prosthodontists
      (ACP) conducted two surveys using a web-based survey engine: one to assess the
      current status of occlusion education in predoctoral dental education and another
      to examine the opinions of faculty and course directors on the content of
      occlusion curriculum. The sections in the surveys included demographic
      information, general curriculum information, occlusion curriculum for dentate
      patients, occlusion curriculum for removable prosthodontics, occlusion curriculum
      for implant prosthodontics, temporomandibular disorder (TMD) curriculum, teaching
      philosophy, concepts taught, and methods of assessment. The results from the
      surveys were compiled and analyzed using descriptive statistics. The results from
      the two surveys on general concepts taught in occlusion curriculum were sorted
      and compared for discrepancies. RESULTS: According to the predoctoral occlusion
      curriculum surveys, canine guidance was preferred for dentate patients, fixed
      prosthodontics, and fixed implant prosthodontics. Bilateral balanced occlusion
      was preferred for removable prosthodontics and removable implant prosthodontics.
      There were minor differences between the two surveys regarding the occlusion
      concepts being taught and the opinions of faculty members teaching occlusion.
      CONCLUSION: Two surveys were conducted regarding the current concepts being
      taught in occlusion curriculum and the opinions of educators on what should be
      taught in occlusion curriculum. An updated and clearly defined curriculum
      guideline addressing occlusion in fixed prosthodontics, removable prosthodontics,
      implant prosthodontics, and TMD is needed.

PMID- 23130598
TI  - Correlation between protrusive interocclusal record and panoramic radiographic
      image: a pilot study.

PMID- 23130600
TI  - 2012 Frechette Awards announced.

PMID- 23130601
TI  - Effect of fluoxetine and pergolide on expression of nucleoside transporters and
      nucleic-related enzymes in mouse brain.
AB  - Nucleoside transporter (NT) and nucleic-related enzyme (NRE) play key roles in
      the physiology of nucleosides and the pharmacology of its analogs in mammals. In
      this study, we examined the effect of fluoxetine, a selective serotonin reuptake
      inhibitor, and pergolide, a dopamine D receptor agonist, on the expression of NTs
      and NREs in mouse brain. It was confirmed by the detection of corresponding mRNAs
      that three equilibrative nucleoside transporter (ENT1-3) isoforms, concentrative
      nucleoside transporter 2 (CNT2), CNT3, adenosine kinase (AK), and apyrase, but
      not CNT1, were expressed in brain tissue. Based on an assessment by mRNA
      determination, the cerebral expression of CNT2 was found to be increased by
      administration of fluoxetine and pergolide to mice. Furthermore, pergolide
      increased the expression of ENT2. However, fluoxetine and pergolide had no
      significant effect on the expression of mRNA for other NTs, AK, and apyrase.
      Therefore, we concluded that the expression of several NT isoforms, but not NREs,
      in mouse brain was affected by treatment with fluoxetine and pergolide. 

PMID- 23130602
TI  - Decorating BODIPY with three- and four-coordinate boron groups.
AB  - Two new BODIPY derivative molecules decorated by a Lewis acidic BMes(2)(vinyl)
      group and a photochromic four-coordinate boryl chromophore, respectively, have
      been synthesized. Significant mutual influence on photophysical and photochemical
      properties by the different boron-containing units has been observed.

PMID- 23130603
TI  - A prospective cohort study of non-fatal accidental overdose among street youth:
      the link with suicidal ideation.
AB  - INTRODUCTION AND AIMS: Drug overdose and suicide are the two leading causes of
      death among street youth. The literature discusses the two faces of drug
      overdose: accidental act and suicide attempt. Some authors have stated that
      accidental overdoses may be a hidden expression of suicidal ideation. This study
      longitudinally examined the relationship between recent suicidal ideations and
      non-fatal accidental drug overdoses among street youth. DESIGN AND METHODS:
      Between July 2001 and December 2005, 858 street youth (14-23 years old) were
      recruited for a prospective cohort study. Youth were eligible if, in the previous
      year, they had been without a place to sleep more than once or had used the
      services of street youth agencies on a regular basis (>=3). Participants
      completed baseline questionnaires and follow-up interviews were carried out every
      6 months. Mixed-effect logistic regression models were conducted. Apart from
      suicidal ideation and accidental drug overdose, variables considered in the model
      were age, sex, problematic alcohol use, homelessness, injection drug use and
      polydrug use (>=3 drugs). RESULTS: Accidental drug overdose was significantly
      associated with suicidal ideation (adjusted odds ratio 1.88; 95% confidence
      interval 1.23-2.54). Homelessness, injection drug use and polydrug use were also
      significant in the final model. DISCUSSION AND CONCLUSIONS: Results show that,
      during follow up, suicidal ideation independently increased risks of accidental
      overdose. They also underscore the need for interventions beyond educational
      prevention. Primary care practitioners should investigate suicidal ideations and
      behaviours of street youth in treatment for accidental overdose.

PMID- 23130604
TI  - Clinical trials in irritable bowel syndrome: a review.
AB  - Irritable bowel syndrome (IBS) is one of the most common gastrointestinal
      disorders and it is characterized by episodes of abdominal pain and altered bowel
      functions. The specific bowel disturbances of diarrhea, constipation or an
      alternation between the two defines the IBS subtypes of diarrhea-predominant,
      constipation-predominant, and mixed or alternating IBS. Because of the
      abnormalities in bowel states associated with each IBS subtype, it is not likely
      that one agent would successfully treat all three subtypes. As a result, clinical
      trials have focused, for the most part, on one IBS subtype. Over the past 2
      decades very few agents have achieved regulatory approval for the treatment of
      IBS. In the present article we review publications reporting on phase 2 and phase
      3 studies evaluating agents to potentially be used in the treatment of patients
      with IBS.

PMID- 23130606
TI  - Maternal nutrition and offspring's adulthood NCD's: a review.
AB  - Overnutrition and undernutrition during pregnancy are closely related to
      pregnancy outcome as well as neonatal and perinatal outcomes. This and more, from
      various published data it seems that the effect of maternal nutrition during
      fetal life stretches far beyond the neonatal period, and influences health issues
      in adulthood, from cardiovascular and metabolic disorders through mental
      illnesses. The purpose of this review is to update about overnutrition and
      undernutrition during pregnancy and their effect on noncommunicable adulthood
      diseases, and about leading theories on the subject.

PMID- 23130607
TI  - Clinical application of a novel automatic algorithm for  actigraphy-based
      activity and rest period identification to  accurately determine awake and asleep
      ambulatory blood pressure parameters and cardiovascular risk.
AB  - This paper reports the results of a study designed to determine whether there are
      statistically significant differences between the values of ambulatory blood
      pressure monitoring (ABPM) parameters obtained using different methods-fixed
      schedule, diary, and automatic algorithm based on actigraphy-of defining the main
      activity and rest periods, and to determine the clinical relevance of such
      differences. We studied 233 patients (98 men/135 women), 61.29 +/- .83 yrs of age
      (mean +/- SD). Statistical methods were used to measure agreement in the
      diagnosis and classification of subjects within the context of ABPM and
      cardiovascular disease risk assessment. The results show that there are
      statistically significant differences both at the group and individual levels.
      Those at the individual level have clinically significant implications, as they
      can result in a different classification, and, therefore, different diagnosis and
      treatment for individual subjects. The use of an automatic algorithm based on
      actigraphy can lead to better individual treatment by correcting the accuracy
      problems associated with the fixed schedule on patients whose actual
      activity/rest routine differs from the fixed schedule assumed, and it also
      overcomes the limitations and reliability issues associated with the use of
      diaries.

PMID- 23130608
TI  - Racial and ethnic disparities in internet use for seeking health information
      among young women.
AB  - To examine the influence of race/ethnicity on seeking health information from the
      Internet among women aged 16-24 years, the authors conducted a self-administered
      survey on 3,181 women regarding their Internet use and obtaining information on
      reproductive health (menstruation, contraception, pregnancy, sexually transmitted
      infections) and general health from the Internet. The authors performed
      multivariate logistic regression to examine the association between
      race/ethnicity and online health-related information seeking after adjusting for
      covariates. Racial/ethnic disparities were noted in overall Internet use and its
      use to locate health information. Overall, more White (92.7%) and Black (92.9%)
      women used the Internet than did Hispanics (67.5%). More White women (79.2%) used
      it to find health information than did Blacks and Hispanics (70.3% and 74.3%,
      respectively). Compared with White women, Blacks and Hispanics were less likely
      to seek information on contraception [(OR 0.73, 95% CI 0.58-0.91) and (OR 0.75,
      95% CI 0.61-0.92)] and more likely to seek information on pregnancy tests [(OR
      1.67, 95% CI 1.28-2.18) and (OR 1.40, 95% CI 1.09-1.81] and sexually transmitted
      infections [(OR 1.39, 95% CI 1.11-1.73) and (OR 1.25, 95% CI 1.01-1.54)],
      respectively. With regard to general health issues-such as how to quit smoking,
      how to lose weight, alcohol/drug use, mood disorders, and skin disorders-Blacks,
      but not Hispanics, were significantly less likely to seek online information than
      were Whites. Disparities in the way that women from different backgrounds use the
      Internet for health-related information could be associated with overall health
      awareness.

PMID- 23130609
TI  - Antibody response in vaccinated pregnant mares to recent G3BP[12] and G14P[12]
      equine rotaviruses.
AB  - BACKGROUND: Both the G3P[12] and the G14P[12] type of equine group A rotavirus
      (RVA) have recently become predominant in many countries, including Japan. G3
      types are classified further into G3A and G3B. The G3A viruses have been
      circulating in Europe, Australia, and Argentina, and the G3B viruses have been
      circulating in Japan. However, only an inactivated vaccine containing a single
      G3BP[12] strain is commercially available in Japan. To assess the efficacy of the
      current vaccine against recently circulating equine RVA strains, we examined
      antibody responses in pregnant mares to recent G3BP[12] and G14P[12] strains by
      virus neutralization test. FINDINGS: After vaccination in five pregnant mares,
      the geometric mean serum titers of virus-neutralizing antibody to recent G3BP[12]
      strains increased 5.3- to 7.0-fold and were similar to that against homologous
      vaccine strain. Moreover, antibody titers to recent G14P[12] strains were also
      increased 3.0- to 3.5-fold. CONCLUSIONS: These results suggest that inoculation
      of mares with the current vaccine should provide foals with virus-neutralizing
      antibodies against not only the G3BP[12] but also the G14P[12] RVA strain via the
      colostrum.

PMID- 23130610
TI  - Heme/copper assembly mediated nitrite and nitric oxide interconversion.
AB  - The heme(a3)/Cu(B) active site of cytochrome c oxidase is responsible for
      cellular nitrite reduction to nitric oxide; the same center can return NO to the
      nitrite pool via oxidative chemistry. Here, we show that a partially reduced
      heme/Cu assembly reduces NO(2)(-) ion, producing nitric oxide. The heme serves as
      the reductant, but the Cu(II) ion is also required. In turn, a MU-oxo heme
      Fe(III)-O-Cu(II) complex facilitates NO oxidation to nitrite; the final products
      are the reduced heme and Cu(II)-nitrito complexes.

PMID- 23130611
TI  - Circulating fatty acid binding protein as a marker of intestinal failure in
      septic patients.

PMID- 23130612
TI  - Immunolocalization of different collagens in the cornea of human fetal eyes: a
      developmental approach.
AB  - PURPOSE: To study the corneal development in the human fetal eye with particular
      emphasis on the epithelial basement membrane and Bowman's layer. Thus,
      immunohistochemical markers supposed to stain this region were employed. MATERIAL
      AND METHODS: 19 formalin-fixed fetal eyes and a 16-day-old newborn's cornea
      without any obvious irregularities of the anterior segment were investigated. The
      age of the fetal eyes ranged from 11 to 38 week of gestation (WoG). The eyes
      (including the corneal thickness) were measured and, in addition to routine
      hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) stains,
      immunohistochemical labeling with antibodies to collagen IV, V, IX, and XVII was
      performed. RESULTS: Analysis of the H&E stains revealed that measurements of
      corneal thickness correlated well with corneal development as a basic indicator
      for maturation. In a more detailed immunohistochemical analysis, collagen IV was
      expressed in the epithelial basement membrane (BM) of the cornea, conjunctiva,
      and Descemet's membrane in fetal eyes up to the age of 23 WoG. In fetal eyes
      older than 23 WoG, staining was confined to the limbal area only. With the
      antibody against collagen V, the corneal stroma and the BM were intensely
      stained. Bowman's layer (first detected at 17 WoG by light microscopy) was not
      labeled. Anti-collagen IX labeled predominantly the conjunctival and corneal
      epithelium. With anti-collagen XVII, the BM of the cornea and conjunctiva was
      stained in all fetal eyes, whereas intracellular expression in the epithelium
      increased with age. CONCLUSION: Our results indicate maturation-associated
      variations of collagen expression in the human cornea. Measurements of the
      corneal thickness may serve as an additional parameter to narrow down the
      developmental age with possible implications for pediatric pathology and forensic
      issues.

PMID- 23130613
TI  - Editorial.

PMID- 23130614
TI  - Bearing the unbearable: ancestral transmission through dreams and moving
      metaphors in the analtyic field.
AB  - This paper explores how untold and unresolved intergenerational trauma may be
      transmitted through unconscious channels of communication, manifesting in the
      dreams of descendants. Unwitting carriers for that which was too horrific for
      their ancestors to bear, descendants may enter analysis through an unconscious
      need to uncover past secrets, piece together ancestral histories before the keys
      to comprehending their terrible inheritance die with their forebears. They seek
      the relational containment of the analytic relationship to provide psychological
      conditions to bear the unbearable, know the unknowable, speak the unspeakable and
      redeem the unredeemable. In the case of 'Rachael', initial dreams gave rise to
      what Hobson (1984) called 'moving metaphors of self' in the analytic field. Dream
      imagery, projective and introjective processes in the transference
      countertransference dynamics gradually revealed an unknown ancestral history. I
      clarify the back and forth process from dream to waking dream thoughts to moving
      metaphors and differentiate the moving metaphor from a living symbol. I argue
      that the containment of the analytic relationship nested within the security of
      the analytic space is a necessary precondition for such healing processes to
      occur.

PMID- 23130615
TI  - Transgenerational transmission of indigestible facts: from trauma, deadly ghosts
      and mental voids to meaning-making interpretations.
AB  - In this paper I will discuss clinical material and make some hypotheses on how to
      work with patients for whom trans-generational transmission of trauma is an
      issue. Basing my hypothesis on two clinical cases, I will propose a way of
      dealing with undigested facts, the fabric of trauma, which generate deadly ghosts
      and mental voids that are transmitted from one generation to the next. I will
      propose a way of formulating interpretations for the unthinkable to become
      thinkable and find a representation in the mind of patients who suffer from
      transgenerationally transmitted trauma. Some thoughts will be given to the
      maternal and the paternal transmitters of trauma in relation to child development
      issues.

PMID- 23130616
TI  - Family myth, the symbolic realm and the ancestors.
AB  - This paper takes the shape of a diptych. The first part explores the ancestors as
      embodied ghosts, internal objects or as mediated through ancestral heritage, as
      these aspects intertwine in a Mobius strip. The second part looks at ancestral
      heritage and the different ways in which 'family myth' appears in a Jungian
      context and in Systemic Psychotherapy (family therapy). Both share an interface
      through the current paradigm shifts towards mutual reflexivity in patient and
      therapist and a focus on the interpersonal space. The ancestors give substance to
      the eternal riddle: 'from whence do we come, who are we and where do we go',
      which connects past, present and future. Our ancestors are part of our minds,
      perhaps in the way Damasio (2010) postulates that ancestral experiences mediated
      through culture shape our brains. The leitmotiv of individuation through mimesis
      (sameness) and alterity (difference) runs through both parts.

PMID- 23130617
TI  - Caught between cultures: cultural norms in Jungian psychodynamic process.
AB  - In our increasingly mobile world, more of us are caught between cultures rather
      than in one culture. We straddle different ethnic, racial, political,
      geographical, and religious groups, forced into awareness of the precarious
      nature of our self-definition, involuntarily gazing at the constructed nature of
      our cultural norms, unable to avoid reckoning with the choices of which
      collective to honour. The impossibility of separating individual from collective
      is foundational to work as Jungian practitioners, but a paradox of individuation
      is becoming free of the control of collective norms while simultaneously living
      within those very norms. In such a conflict it becomes easy to overlook the fact
      that when the norms we have incorporated into ourselves are from cultures vastly
      different from the one in which we live, the cacophony can be overwhelming. In
      this paper, I will draw from postmodern theorists such as Derrida, Foucault and
      Irigaray in an effort to re-imagine the role of culture in psychodynamic process.
      The case of a Muslim Iranian man working with a Christian American woman analyst
      will be used to explore the complexity of a multitude of cultural norms present
      in the consulting room.

PMID- 23130626
TI  - Synthesis and SAR of b-annulated 1,4-dihydropyridines define cardiomyogenic
      compounds as novel inhibitors of TGFbeta signaling.
AB  - A medium-throughput murine embryonic stem cell (mESC)-based high-content
      screening of 17000 small molecules for cardiogenesis led to the identification of
      a b-annulated 1,4-dihydropyridine (1,4-DHP) that inhibited transforming growth
      factor beta (TGFbeta)/Smad signaling by clearing the type II TGFbeta receptor
      from the cell surface. Because this is an unprecedented mechanism of action, we
      explored the series' structure-activity relationship (SAR) based on TGFbeta
      inhibition, and evaluated SAR aspects for cell-surface clearance of TGFbeta
      receptor II (TGFBR2) and for biological activity in mESCs. We determined a
      pharmacophore and generated 1,4-DHPs with IC(50)s for TGFbeta inhibition in the
      nanomolar range (e.g., compound 28, 170 nM). Stereochemical consequences of a
      chiral center at the 4-position was evaluated, revealing 10- to 15-fold more
      potent TGFbeta inhibition for the (+)- than the (-) enantiomer. This
      stereopreference was not observed for the low level inhibition against Activin A
      signaling and was reversed for effects on calcium handling in HL-1 cells.

PMID- 23130627
TI  - Variant rs2200733 on chromosome 4q25 confers increased risk of atrial
      fibrillation: evidence from a meta-analysis.
AB  - INTRODUCTION: Several genome-wide association studies have identified rs2200733,
      a single-nucleotide polymorphism (SNP) at 4q25 to be the most common chromosomal
      variant present in patients with atrial fibrillation (AF). We aimed to explore
      the association of rs2200733 with AF through a systematic review and meta
      analysis. METHOD: An extensive literature search was performed on PubMed, and
      other databases using the key words "genetics" and "AF." Seven case-control
      studies evaluating the association via multivariate analysis were identified
      including a total of 83,335 subjects (10,546 with AF, 72,789 referent individuals
      without AF). Meta-analytic estimates were derived using random effects models.
      Potential sources of heterogeneity were examined in sensitivity analyses, and
      publication biases were estimated. RESULT: At pooled analysis, there was a strong
      independent association between the variant rs2200733 and the risk of AF (OR 1.89
      [95% CI 1.62-2.16], P < 0.001). Minor allelic frequencies for SNP rs22000733 were
      significantly more prevalent in AF population than non-AF. Metaregression results
      revealed that country of descent (logOR 0.38, P = 0.45) or site of study (logOR: 
      0.16, P = 0.41) did not moderate the overall effect size. CONCLUSION: Variant
      rs2200733 on chromosome 4q25 independently confers increased risk of AF. This
      finding will aid in improving our understanding of AF pathophysiology, risk
      prediction, and stratification of treatment strategy.

PMID- 23130629
TI  - Supramolecular organization in self-assembly of chromatin and cationic lipid
      bilayers is controlled by membrane charge density.
AB  - In this work we have investigated the structures of aggregates formed in model
      systems of dilute aqueous mixtures of "model chromatin" consisting of either
      recombinant nucleosome core particles (NCPs) or nucleosome arrays consisting of
      12 NCPs connected with 30 bp linker DNA, and liposomes made from different
      mixtures of cationic and zwitterionic lipids, 1,2-dioleoyl-3-trimethylammonium
      propane chloride salt (DOTAP) and 1,2-dioleoyl-sn-glycero-3-phosphocholine
      (DOPC). The aggregates formed were characterized using different optical
      microscopy methods and small-angle X-ray scattering (SAXS), and the results are
      discussed in terms of the competing intermolecular interactions among the
      components. For a majority of the samples, the presence of lamellar structures
      could be identified. In samples with high fractions of DOTAP in the liposomes,
      well-defined lamellar structures very similar to those formed by the
      corresponding lipid mixtures and DNA alone (i.e., without histone proteins) were
      observed; in these aggregates, the histones are expelled from the model
      chromatin. The findings suggest that, with liposomes containing large fractions
      of cationic lipid, the dominating driving force for aggregation is the increase
      in translational entropy from the release of counterions, whereas with lower
      fractions of the cationic lipid, the entropy of mixing of the lipids within the
      bilayers results in a decreased DNA-lipid attraction.

PMID- 23130630
TI  - Psychological impact of stillbirths on obstetricians.
AB  - OBJECTIVE: To assess the psychological impact on US obstetricians when they care
      for women who have suffered a stillbirth and explore whether demographic (e.g.
      age, gender) and practice (e.g. number of patients, practice type) variables were
      related to the extent of psychological impact for obstetricians following
      stillbirth. METHODS: Using a questionnaire that could be completed in about 20
      min, we surveyed 1000 American College of Obstetricians and Gynecologists (ACOG)
      members. Physicians were asked about how stillbirths have affected them
      personally. RESULTS: Half of those surveyed responded (499) and of those 365
      currently practiced obstetrics. Virtually all obstetricians have looked after
      women who have had a stillbirth. Grief was the most common reaction experienced
      with 53.7% reporting that they personally "very much" experienced grief. Other
      common and significant reactions were self-doubt (17.2%), depression (16.9%) and
      self-blame (16.4%). Significant psychological impact on the obstetrician was
      associated with older age, solo practice, higher volume practices and higher
      proportion of Medicaid patients; gender was not found to be associated with
      psychological impact when controlling for age. Further, greater self-reported
      performance and training regarding maternal and family counseling, management of
      stillbirth, and knowledge of stillbirth evaluation was associated with greater
      levels of grief. CONCLUSION: Physician grief is a common reaction among
      obstetricians after caring for a patient who has had a stillbirth.

PMID- 23130628
TI  - Associations of the FTO rs9939609 and the MC4R rs17782313 polymorphisms with type
      2 diabetes are modulated by diet, being higher when adherence to the
      Mediterranean diet pattern is low.
AB  - BACKGROUND: Although the fat mass and obesity (FTO) and melanocortin-4 receptor
      (MC4R) genes have been consistently associated with obesity risk, the association
      between the obesity-risk alleles with type 2 diabetes is still controversial. In
      some recent meta-analyses in which significant results have been reported, the
      associations disappeared after adjustment for body mass index (BMI). However gene
      diet interactions with dietary patterns have not been investigated. Our main aim
      was to analyze whether these associations are modulated by the level of adherence
      to the Mediterranean Diet (MedDiet). METHODS: Case-control study in 7,052 high
      cardiovascular risk subjects (3,430 type 2 diabetes cases and 3,622 non-diabetic
      subjects) with no differences in BMI. Diet was assessed by validated
      questionnaires. FTO-rs9939609 and MC4R-rs17782313 were determined. An aggregate
      genetic score was calculated to test additive effects. Gene-diet interactions
      were analyzed. RESULTS: Neither of the polymorphisms was associated with type 2
      diabetes in the whole population. However, we found consistent gene-diet
      interactions with adherence to the MedDiet both for the FTO-rs9939609 (P
      interaction=0.039), the MC4R-rs17782313 (P-interaction=0.009) and for their
      aggregate score (P-interaction=0.006). When adherence to the MedDiet was low,
      carriers of the variant alleles had higher type 2 diabetes risk (OR=1.21, 95%CI:
      1.03-1.40; P=0.019 for FTO-rs9939609 and OR=1.17, 95%CI:1.01-1.36; P=0.035 for
      MC4R-rs17782313) than wild-type subjects. However, when adherence to the MedDiet
      was high, these associations disappeared (OR=0.97, 95%CI: 0.85-1.16; P=0.673 for
      FTO-rs9939609 and OR=0.89, 95%CI:0.78-1.02; P=0.097 for MC4R-rs17782313). These
      gene-diet interactions remained significant even after adjustment for BMI. As
      MedDiet is rich in folate, we also specifically examined folate intake and
      detected statistically significant interaction effects on fasting plasma glucose
      concentrations in non-diabetic subjects. However these findings should be
      interpreted with caution because folate intake may simply reflect a healthy
      dietary pattern. CONCLUSIONS: These novel results suggest that the association of
      the FTO-rs9939609 and the MC4R-rs17782313 polymorphisms with type 2 diabetes
      depends on diet and that a high adherence to the MedDiet counteracts the genetic
      predisposition.

PMID- 23130631
TI  - Controlling a nanowire quantum dot band gap using a straining dielectric
      envelope.
AB  - We tune the emission wavelength of an InAsP quantum dot in an InP nanowire over
      200 meV by depositing a SiO(2) envelope using plasma-enhanced chemical vapor
      deposition without deterioration of the optical quality. This SiO(2) envelope
      generates a controlled static strain field. Both red and blue shift can be easily
      achieved by controlling the deposition conditions of the SiO(2). Using atomistic
      empirical tight-binding calculations, we investigate the effect of strain on a
      quantum dot band structure for different compositions, shape, and crystal
      orientations. From the calculations, we estimate the applied strain in our
      experiment. This enables engineering of the band gap in nanowires with
      unprecedented possibilities to extend the application range of nanowire devices.

PMID- 23130632
TI  - p16 immunohistochemistry alone is a better prognosticator in tonsil cancer than
      human papillomavirus in situ hybridization with or without p16
      immunohistochemistry.
AB  - CONCLUSIONS: p16 immunohistochemistry (IHC) status correlated with less exposure
      to smoking and/or alcohol in Korean patients with locally advanced tonsillar
      squamous cell carcinoma (TSCC), and was an independent prognostic factor for
      survival. OBJECTIVE: TSCC is more likely to be human papillomavirus (HPV)
      positive than other head and neck squamous cell carcinoma (HNSCC) subtypes. The
      objective of this study was to ascertain the HPV status of TSCC in Korean
      patients and to determine its relationship with clinical parameters and
      prognosis. METHODS: The locally advanced TSCCs of 79 patients who were treated
      between 2000 and 2008 were tested by p16 IHC and HPV in situ hybridization (ISH)
      with a tissue microarray. RESULTS: Sixty-three patients (80%) were positive for
      p16 IHC, while 54 (68%) were positive by HPV ISH. p16 IHC status correlated
      significantly with lower exposure to smoking and alcohol (p < 0.05) but did not
      correlate with T and N stage classification, histological differentiation, age,
      or gender. The p16-positive group had a significantly higher 5-year overall
      survival rate in comparison with the p16-negative group (78% vs 63%, hazard ratio
      (HR) = 0.347, 95% CI = 0.14, 95% Cp = 0.025). p16 IHC was a favorable independent
      prognostic factor for overall survival, even after adjustment for age and T stage
      (HR = 0.283, 95% CI = 0.103, 95% p = 0.015).

PMID- 23130633
TI  - Oxidative difunctionalization of 2-amino-4H-pyrans in iodobenzene diacetate and N
      chlorosuccinimide: reactivity, mechanistic insights, and DFT calculations.
AB  - Oxidative difunctionalization of 2-amino-4H-pyrans was accomplished with
      iodobenzene diacetate (IBD) and N-chlorosuccinimide (NCS) reagents in alcoholic
      medium. 2-Amino-4H-pyrans undergo geminal dialkoxylation with the migration of an
      amino group (1a,b, 2a-i, 3a,b, and 4) in IBD, whereas with NCS addition of both
      chlorine and alkoxy groups takes place across the chromene double bond (6a-i).

PMID- 23130634
TI  - Polymer-bound pyrene-4,5,9,10-tetraone for fast-charge and -discharge lithium-ion
      batteries with high capacity.
AB  - Organic rechargeable batteries have received significant research interest from
      the viewpoints of structural diversity and sustainability of electrode materials.
      We designed core structures of organic cathode materials for lithium-ion (Li-ion)
      batteries based on density functional theory (DFT) calculations, which indicated
      that six-membered cyclic 1,2-diketones serve as excellent core structures because
      of the high redox energy change resulting from favorable coordination of the
      oxygen atoms to Li and the aromaticity of the reduced form. Here, we show that
      the Li-ion battery composed of pyrene-4,5,9,10-tetraone (PYT), which has two six
      membered cyclic 1,2-diketone units, bound to polymethacrylate exhibits remarkable
      charge-discharge properties with a high specific capacity of 231 mAh/g, excellent
      rechargeability (83% of the capacity retained after 500 cycles), and charge
      discharge ability (90% of the capacity at 30 C as compared to 1 C) in the
      LiNTf(2)/tetraglyme ionic-liquid system.

PMID- 23130635
TI  - The use of continuous data versus binary data in MTC models: a case study in
      rheumatoid arthritis.
AB  - BACKGROUND: Estimates of relative efficacy between alternative treatments are
      crucial for decision making in health care. When sufficient head to head evidence
      is not available Bayesian mixed treatment comparison models provide a powerful
      methodology to obtain such estimates. While models can be fit to a broad range of
      efficacy measures, this paper illustrates the advantages of using continuous
      outcome measures compared to binary outcome measures. METHODS: Using a case study
      in rheumatoid arthritis a Bayesian mixed treatment comparison model is fit to
      estimate the relative efficacy of five anti-TNF agents currently licensed in
      Europe. The model is fit for the continuous HAQ improvement outcome measure and a
      binary version thereof as well as for the binary ACR response measure and the
      underlying continuous effect. Results are compared regarding their power to
      detect differences between treatments. RESULTS: Sixteen randomized controlled
      trials were included for the analysis. For both analyses, based on the HAQ
      improvement as well as based on the ACR response, differences between treatments
      detected by the binary outcome measures are subsets of the differences detected
      by the underlying continuous effects. CONCLUSIONS: The information lost when
      transforming continuous data into a binary response measure translates into a
      loss of power to detect differences between treatments in mixed treatment
      comparison models. Binary outcome measures are therefore less sensitive to change
      than continuous measures. Furthermore the choice of cut-off point to construct
      the binary measure also impacts the relative efficacy estimates.

PMID- 23130636
TI  - Nuclear factor kappaB down-regulates human UDP-glucuronosyltransferase 1A1: a
      novel mechanism involved in inflammation-associated hyperbilirubinaemia.
AB  - Jaundice or hyperbilirubinaemia is a common complication of sepsis. UGT1A1 (UDP
      glucuronosyltransferase 1A1) is a critical gene for bilirubin metabolism and
      irinotecan detoxification. However, the molecular pathogenesis of
      hyperbilirubinaemia during inflammation needs to be further clarified. Human
      hepatic UGT1A1 expression was analysed by RT (reverse transcription)-PCR, qRT-PCR
      (quantitative real-time PCR) and Western blotting in response to LPS
      (lipopolysaccharide) stimulation. Transcription regulatory elements in the
      upstream promoter region of the human UGT1A1 gene were determined using EMSA
      (electrophoretic mobility-shift assay) and ChIP (chromatin immunoprecipitation).
      The important role of the transcription regulatory element was examined using a
      luciferase assay, and was determined by qRT-PCR using a transcription factor
      activation inhibitor. LPS down-regulated the UGT1A1 mRNA expression in human
      hepatoma cell lines. A newly identified NF-kappaB (nuclear factor kappaB)-binding
      site was located on the upstream promoter region (-725/-716) of the human UGT1A1
      gene. LPS-induced NF-kappaB activation and specific binding to the NF-kappaB
      binding site can suppress human UGT1A1 promoter activity and human UGT1A1
      expression. We demonstrated that LPS mediates the suppression of human UGT1A1
      expression through specific binding of NF-kappaB to this newly identified NF
      kappaB-binding site in the upstream promoter of the human UGT1A1 gene. The
      present study may partly explain the molecular pathogenesis of inflammation
      associated hyperbilirubinaemia.

PMID- 23130637
TI  - Rational design of bioactive, modularly assembled aminoglycosides targeting the
      RNA that causes myotonic dystrophy type 1.
AB  - Myotonic dystrophy type 1 (DM1) is caused when an expanded r(CUG) repeat
      (r(CUG)(exp)) binds the RNA splicing regulator muscleblind-like 1 protein (MBNL1)
      as well as other proteins. Previously, we reported that modularly assembled small
      molecules displaying a 6'-N-5-hexynoate kanamycin A RNA-binding module (K) on a
      peptoid backbone potently inhibit the binding of MBNL1 to r(CUG)(exp). However,
      these parent compounds are not appreciably active in cell-based models of DM1.
      The lack of potency was traced to suboptimal cellular permeability and
      localization. To improve these properties, second-generation compounds that are
      conjugated to a d-Arg(9) molecular transporter were synthesized. These modified
      compounds enter cells in higher concentrations than the parent compounds and are
      efficacious in cell-based DM1 model systems at low micromolar concentrations. In
      particular, they improve three defects that are the hallmarks of DM1: a
      translational defect due to nuclear retention of transcripts containing
      r(CUG)(exp); pre-mRNA splicing defects due to inactivation of MBNL1; and the
      formation of nuclear foci. The best compound in cell-based studies was tested in
      a mouse model of DM1. Modest improvement of pre-mRNA splicing defects was
      observed. These studies suggest that a modular assembly approach can afford
      bioactive compounds that target RNA.

PMID- 23130638
TI  - Impact of a multimodal intervention to reduce bloodstream infections related to
      vascular catheters in non-ICU wards: a multicentre study.
AB  - To determine the impact of a multimodal intervention designed to reduce the
      incidence of catheter-related bloodstream infections (CRBSIs) outside the ICU, we
      conducted a prospective, quasi-experimental, before-after intervention study in
      11 hospitals participating in the VINCat programme in Catalonia, Spain. The
      intervention consists of: (i) an evidence-based bundle of practices relating to
      catheter insertion and maintenance; (ii) a training programme for healthcare
      workers; (iii) four point-prevalence surveys to track the status of the
      catheters; and (iv) feedback reports to the staff involved. The study included
      both central (CVC) and peripheral venous catheters (PVCs). Rates of CRBSI per
      1000 patient-days were prospectively measured in 2009 (pre-intervention period)
      and 2010 (post-intervention period). The analysis included 1 191 843 patient-days
      in 2009 and 1 173 672 patient-days in 2010. The overall incidence of CRBSI
      decreased from 0.19 to 0.15 (p 0.04) and the incidence of CRBSI associated with a
      CVC decreased from 0.14 to 0.10 (p 0.004) after the intervention. The incidence
      in PVCs remained unchanged. There was a statistically significant improvement in
      the adequate maintenance of both CVCs and PVCs. Among the CRBSIs originating in
      PVCs, 61.8% appeared more than 72 h every insertion. There was a lower infection
      rate in the hospitals with a higher adherence to the recommendation to replace
      PVCs after 72 h. Our findings suggest that the implementation of intervention
      programmes similar to ours could have a major impact on patient safety by
      reducing the incidence of CRBSIs, and that routine replacement of PVCs might
      additionally prevent a significant number of bloodstream infections.

PMID- 23130639
TI  - Black and white and read all over: the past, present and future of giant panda
      genetics.
AB  - Few species attract much more attention from the public and scientists than the
      giant panda (Ailuropoda melanoleuca), a popular, enigmatic but highly endangered
      species. The application of molecular genetics to its biology and conservation
      has facilitated surprising insights into the biology of giant pandas as well as
      the effectiveness of conservation efforts during the past decades. Here, we
      review the history of genetic advances in this species, from phylogeny,
      demographical history, genetic variation, population structure, noninvasive
      population census and adaptive evolution to reveal to what extent the current
      status of the giant panda is a reflection of its evolutionary legacy, as opposed
      to the influence of anthropogenic factors that have negatively impacted this
      species. In addition, we summarize the conservation implications of these genetic
      findings applied for the management of this high-profile species. Finally, on the
      basis of these advances and predictable future changes in genetic technology, we
      discuss future research directions that seem promising for giant panda biology
      and conservation.

PMID- 23130644
TI  - Total synthesis, structure, and oral absorption of a thiazole cyclic peptide,
      sanguinamide A.
AB  - The first total synthesis and three-dimensional solution structure are reported
      for sanguinamide A, a thiazole-containing cyclic peptide from the sea slug H.
      sanguineus. Solution phase fragment synthesis, solid phase fragment assembly, and
      solution macrocyclization were combined to give (1) in 10% yield. Spectral
      properties were identical for the natural product, requiring revision of its
      structure from (2) to (1). Intramolecular transannular hydrogen bonds help to
      bury polar atoms, which enables oral absorption from the gut.

PMID- 23130645
TI  - Cord blood oxidative stress markers correlate with umbilical artery pulsatility
      in fetal growth restriction.
AB  - OBJECTIVE: To compare cord blood oxidative stress markers (OSM) between
      intrauterine small fetuses with high umbilical artery (UA) Doppler indices and
      normal indices. METHODS: Forty women who had oligohydramnios and intrauterine
      growth-restricted fetuses with abnormal (n = 20, group I) or normal Doppler
      indices (n = 20, group II) were included. All patients underwent fetal Doppler
      ultrasound studies. Cord blood was collected at birth and six OSMs (ischemia
      modified albumin (IMA), hepatocyte growth factor (HGF), malondialdehyde (MDA))
      levels, total oxidant status (TOS), total antioxidant status (TAS), and oxidative
      stress index (OSI) were studied. RESULTS: The mean cord blood IMA, MDA, TOS, and
      OSI values for group I were significantly increased when compared to the group II
      (p < 0.001 for IMA, MDA, TOS, and OSI). However the mean cord blood HGF and TAS
      values were statistically significantly decreased in group I, compared with group
      II (p < 0.001 for HGF, and TAS). A significant positive (for IMA, MDA,TOS levels,
      and OSI ratio) and negative (for HGF and TAS levels) correlations between UA
      pulsatility index (PI) and cord blood OSM were found. CONCLUSION: The correlation
      between cord blood OSM and Doppler blood flow changes shown in this study may
      contribute to understanding the underlying oxidative stress-related mechanisms.

PMID- 23130646
TI  - Factors affecting chronotype of adolescents in the north according to multiple
      regression analysis.

PMID- 23130647
TI  - Critical role of suspension media in electrophoretic deposition: the example of
      low loss dielectric BaNd2Ti5O14 thick films.
AB  - The importance of electrophoretic deposition (EPD) is well recognized for thick
      film technology, but unfortunately there is no universal suspension medium for
      the EPD of oxides. Thus, the selection of the medium, the stability of the
      suspensions, and the control of the particle potentials, critical for a good
      deposition, need to be established for each new material being processed by EPD.
      In this article, we investigate the key parameters, studying the electrochemistry
      of BaNd(2)Ti(5)O(14) (BNT) suspensions, and establish relationships between
      suspension media, EPD process conditions, microstructure of the deposits, and
      resulting electrical properties of the BNT films. Suspension stability of water,
      ethanol, acetic acid, and acetone-based media was analyzed in terms of zeta
      potential, particle size distribution, UV transmittance, and inductively coupled
      plasma spectrometry. The highest absolute zeta potential values determined for
      acetone with I(2) and acetic acid media are in good agreement with the high
      stability, small and narrow particle size distribution, and low UV light
      transmittance measured for these suspensions. Very high quality thick deposits
      were consequently achieved. However, it was demonstrated that aging of the acetic
      acid-based suspension have serious negative effects on the EPD process for BNT
      materials, including leaching of the metallic elements with a consequent
      modification of the material stoichiometry, change of the conductivity of the
      suspension, and degradation of the films microstructure. These facts severely
      restrict the use of acetic acid. Our results clearly indicate that, besides the
      stability of the suspension, the electrochemistry and aging behavior are key
      aspects for the EPD of functional oxides. Our systematic approach could be viewed
      as providing a set of guidelines for the development of EPD of other oxides.

PMID- 23130648
TI  - Transparency and the Food and Drug Administration--a quantitative study.
AB  - In Europe and North America, there is increasing political pressure being put on
      health regulatory agencies to become more transparent. To date, however, there
      has been little academic evaluation--let alone analysis--of these transparency
      initiatives from a risk communication perspective. This review examines whether
      the U.S. Food and Drug Administration's Adverse Event Reporting System quarterly
      signal postings, put in place after the passage of the Food and Drug
      Administration Amendments Act 2007, will assist patients and doctors in their
      decision-making processes, on the basis of results of a quantitative Internet
      survey of 433 physicians and 1,000 American adults. The results indicate that
      there is significant disagreement between physicians and the public about when
      medical safety issues should be communicated in the first place, with physicians
      opposed to early signal postings while the public in general is in favor. In
      addition the findings show that if the public were to find their drugs listed on
      the Adverse Event Reporting System signals web postings, more than a quarter
      would stop taking their medicine. Going forward, the Food and Drug Administration
      needs to work to a greater degree with social scientists in developing scientific
      based communication strategies, rather than developing transparency initiatives
      on the basis of stakeholder consultations.

PMID- 23130649
TI  - A flow cytometry-based workflow for detection and quantification of anti
      plasmodial antibodies in vaccinated and naturally exposed individuals.
AB  - BACKGROUND: Antibodies play a central role in naturally acquired immunity against
      Plasmodium falciparum. Current assays to detect anti-plasmodial antibodies
      against native antigens within their cellular context are prone to bias and
      cannot be automated, although they provide important information about natural
      exposure and vaccine immunogenicity. A novel, cytometry-based workflow for
      quantitative detection of anti-plasmodial antibodies in human serum is presented.
      METHODS: Fixed red blood cells (RBCs), infected with late stages of P. falciparum
      were utilized to detect malaria-specific antibodies by flow cytometry with
      subsequent automated data analysis. Available methods for data-driven analysis of
      cytometry data were assessed and a new overlap subtraction algorithm (OSA) based
      on open source software was developed. The complete workflow was evaluated using
      sera from two GMZ2 malaria vaccine trials in semi-immune adults and pre-school
      children residing in a malaria endemic area. RESULTS: Fixation, permeabilization,
      and staining of infected RBCs were adapted for best operation in flow cytometry.
      As asexual blood-stage vaccine candidates are designed to induce antibody
      patterns similar to those in semi-immune adults, serial dilutions of sera from
      heavily exposed individuals were compared to naive controls to determine optimal
      antibody dilutions. To eliminate investigator effects introduced by manual
      gating, a non-biased algorithm (OSA) for data-driven gating was developed. OSA
      derived results correlated well with those obtained by manual gating (r between
      0.79 and 0.99) and outperformed other model-driven gating methods. Bland-Altman
      plots confirmed the agreement of manual gating and OSA-derived results. A 1.33
      fold increase (p=0.003) in the number of positive cells after vaccination in a
      subgroup of pre-school children vaccinated with 100 MUg GMZ2 was present and in
      vaccinated adults from the same region we measured a baseline-corrected 1.23
      fold, vaccine-induced increase in mean fluorescence intensity of positive cells
      (p=0.03). CONCLUSIONS: The current workflow advances detection and quantification
      of anti-plasmodial antibodies through improvement of a bias-prone, low-throughput
      to an unbiased, semi-automated, scalable method. In conclusion, this work
      presents a novel method for immunofluorescence assays in malaria research.

PMID- 23130650
TI  - Distribution and fate of HCH isomers and DDT metabolites in a tropical
      environment-case study Cameron Highlands-Malaysia.
AB  - BACKGROUND: The serious impact effects of persistent organic pollutants such as
      organochlorine pesticides, especially dichlorodiphenyltrichloroethane family
      (DDTs) and hexachlorocyclohexane isomers (HCHs) have been causing widespread
      concern, despite effective control on their manufacturing, agricultural and
      vector practices. In that, in addition to the previous global limitations on DDTs
      usage, alpha-HCH, beta-HCH and lindane have also became an on-going topic of
      global relevance based on the latest Stockholm Convention list on 10th of May
      2009. Concentrations of dichlorodiphenyltrichloroethane family (DDTs) and
      hexachlorocyclohexane isomers (HCHs) were determined by GC-ECD in Cameron
      Highlands, the main vegetables and flowers farming area in Malaysia as an
      agricultural tropical environment. A total of 112 surface water and sediment
      samples at eight points were collected along the main rivers in the area namely
      Telom and Bertam in the dry and wet seasons of 2011. RESULTS: Total concentration
      of HCH isomers ranged from not detected to 25.03 ng/L in the water (mean of 5.55
      +/-6.0 ng/L), while, it ranged from 0.002 to 59.17 ng/g (mean of 8.06+/-9.39
      ng/g) in the sediment. Total concentration of DDT and its metabolites in the
      water samples varied from not detected to 8.0 ng/L (mean of 0.90+/-1.66 ng/g),
      whereas, it was in the range of 0.025 to 23.24 ng/g (mean of 2.55+/-4.0 ng/g) in
      the surface sediment samples. The ratio of HCHs and DDTs composition indicated an
      obvious historical usage and new inputs of these pesticides. Among alpha, beta,
      gamma and delta isomers of HCH, gamma was the most dominant component in the
      sediment and water as well. Some seasonal variations in the level of selected
      pesticides were noted. CONCLUSIONS: The results illustrate distribution,
      behaviour and fate of HCHs, and DDTs have closely connected with topological and
      meteorological properties of the area beyond their chemical characterizations.
      The features of environmental circumstances exceed one or more of these
      characters in importance than the other. Although the results show that the
      situation is better than 1998, the impact of persistent agrochemicals such as
      lindane and 4,4'DDE are revealed in a key tropical area of Malaysia.

PMID- 23130651
TI  - From antisocial behavior to violence: a model for the amplifying role of coercive
      joining in adolescent friendships.
AB  - BACKGROUND: Aggression is one of the more stable characteristics of child and
      adolescent development, and violent behavior in early adulthood is often
      foreshadowed by aggressive behavior in childhood and early adolescence.
      Considerable evidence has linked coercive family interactions to aggressive
      behavior in childhood, but less research has been conducted on the joint role of
      family and peer interaction in the escalation of aggression to violence in
      adulthood. METHODS: We coded family interactions at age 12-13 and friendship
      interaction at age 16-17 in a multiethnic sample of youth and families. Violence
      in young adulthood (age 22-23) was measured using self-report, criminal records,
      and parent report. We tested the hypothesis that a process of 'coercive joining'
      in friendship interactions mediated the relationship between coercive family
      interactions and serious violence. RESULTS: We found that observed coercive
      joining in friendships at age 16-17 predicted early-adulthood violent behavior
      over and above an established tendency toward antisocial behavior. We also found
      that observed coercive family interactions at age 12 predicted early-adulthood
      violence, and that coercive joining with friends fully mediated this link.
      CONCLUSIONS: These results significantly extend coercion theory by suggesting
      that coercive joining in the context of peer groups is an additional mechanism by
      which coercive processes in the family are extended and amplified to violent
      behavior in early adulthood. Our findings suggest the importance of addressing
      both individual interpersonal skills and self-organizing peer groups when
      intervening to prevent violent behavior.

PMID- 23130653
TI  - Synthesis of a chiral C2-symmetric sterically hindered pyrrolidine nitroxide
      radical via combined iterative nucleophilic additions and intramolecular 1,3
      dipolar cycloadditions to cyclic nitrones.
AB  - A sterically hindered bis-spirocyclic C(2)-symmetric chiral pyrrolidine-type
      nitroxide has been successfully synthesized starting from an l-tartaric derived
      nitrone. Starting from a pyrrolidine flanked by two methylene groups, complete
      quaternization of the two alpha-carbon atoms has been accomplished through
      iteration of completely regio- and stereoselective intramolecular cycloaddition
      reactions and organometallic additions to key nitrone intermediates, formed in
      turn by oxidation procedures. This method appears to be very useful for building
      up bulky spirocyclic moieties adjacent to a nitroxide group and provides an
      important supplementation to traditional methods of nitroxide synthesis. The
      synthesized chiral nitroxide showed a very high stability to reduction with
      ascorbate (k ~ 8 * 10(-3) M(-1) s(-1)).

PMID- 23130652
TI  - Angiotensin-converting enzyme inhibition curbs tyrosine nitration of
      mitochondrial proteins in the renal cortex during the early stage of diabetes
      mellitus in rats.
AB  - Experiments were performed to evaluate the hypothesis that ACE (angiotensin
      converting enzyme) inhibition (enalapril) suppresses 3-NT (3-nitrotyrosine)
      production in the renal cortex during the early stage of Type 1 DM (diabetes
      mellitus) in the rat. Enalapril was administered chronically for 2 weeks to
      subsets of STZ (streptozotocin)-induced DM and vehicle-treated sham rats. O(2)(-)
      (superoxide anion) and NO(x) (nitrate+nitrite) levels were measured in the media
      bathing renal cortical slices after 90 min incubation in vitro. SOD (superoxide
      dismutase) activity and 3-NT content were measured in the renal cortex
      homogenate. Renal cortical nitrated protein was identified by proteomic analysis.
      Renal cortical production of O(2)(-) and 3-NT was increased in DM rats; however,
      enalapril suppressed these changes. DM rats also exhibited elevated renal
      cortical NO(x) production and SOD activity, and these changes were magnified by
      enalapril treatment. 2-DE (two-dimensional gel electrophoresis)-based Western
      blotting revealed more than 20 spots with positive 3-NT immunoreactivity in the
      renal cortex of DM rats. Enalapril treatment blunted the DM-induced increase in
      tyrosine nitration of three proteins ACO2, GDH1 and MMSDH (aconitase 2, glutamate
      dehydrogenase 1 and methylmalonate-semialdehyde dehydrogenase), each of which
      resides in mitochondria. These data are consistent with enalapril preventing DM
      induced tyrosine nitration of mitochondrial proteins by a mechanism involving
      suppression of oxidant production and enhancement of antioxidant capacity,
      including SOD activation.

PMID- 23130654
TI  - Hypoglycaemia risk with insulin degludec compared with insulin glargine in type 2
      and type 1 diabetes: a pre-planned meta-analysis of phase 3 trials.
AB  - AIM: Hypoglycaemia and the fear of hypoglycaemia are barriers to achieving
      normoglycaemia with insulin. Insulin degludec (IDeg) has an ultra-long and stable
      glucose-lowering effect, with low day-to-day variability. This pre-planned meta
      analysis aimed to demonstrate the superiority of IDeg over insulin glargine
      (IGlar) in terms of fewer hypoglycaemic episodes at equivalent HbA1c in type 2
      and type 1 diabetes mellitus (T2DM/T1DM). METHODS: Pooled patient-level data for
      self-reported hypoglycaemia from all seven (five in T2DM and two in T1DM)
      randomized, controlled, phase 3a, treat-to-target trials in the IDeg clinical
      development programme comparing IDeg once-daily (OD) vs. IGlar OD were analysed.
      RESULTS: Four thousand three hundred and thirty subjects (2899 IDeg OD vs. 1431
      IGlar OD) were analysed. Among insulin-naive T2DM subjects, significantly lower
      rates of overall confirmed, nocturnal confirmed and severe hypoglycaemic episodes
      were reported with IDeg vs. IGlar: estimated rate ratio (RR):0.83[0.70;0.98](95%)
      (CI) , RR:0.64[0.48;0.86](95%) (CI)  and RR:0.14[0.03;0.70](95%) (CI) . In the
      overall T2DM population, significantly lower rates of overall confirmed and
      nocturnal confirmed episodes were reported with IDeg vs. IGlar
      [RR:0.83[0.74;0.94](95%) (CI)  and RR:0.68[0.57;0.82](95%) (CI) ). In the T1DM
      population, the rate of nocturnal confirmed episodes was significantly lower with
      IDeg vs. IGlar during maintenance treatment (RR:0.75[0.60;0.94](95%) (CI) ).
      Reduction in hypoglycaemia with IDeg vs. IGlar was more pronounced during
      maintenance treatment in all populations. CONCLUSIONS: The limitations of this
      study include the open-label design and exclusion of subjects with recurrent
      severe hypoglycaemia. This meta-analysis confirms that similar improvements in
      HbA1c can be achieved with fewer hypoglycaemic episodes, particularly nocturnal
      episodes, with IDeg vs. IGlar across a broad spectrum of patients with diabetes.

PMID- 23130655
TI  - Locally delivered 1% metformin gel in the treatment of smokers with chronic
      periodontitis: a randomized controlled clinical trial.
AB  - BACKGROUND: Metformin (MF) (1,1-dimethylbiguanide HCl) is one of the most
      commonly used oral antihyperglycemic agents for the treatment of type 2 diabetes
      mellitus. Recently, MF has been shown to have bone-sparing properties. The
      present study is designed to investigate the effectiveness of MF 1% in an
      indigenously prepared, biodegradable, controlled-release gel, as an adjunct to
      scaling and root planing (SRP) in treatment of vertical defects in smokers with
      generalized chronic periodontitis (CP). METHODS: Fifty patients were categorized
      into two treatment groups: SRP plus 1% MF and SRP plus placebo. Clinical
      parameters were recorded at baseline and at 3 and 6 months; they included plaque
      index (PI), modified sulcus bleeding index (mSBI), probing depth (PD), and
      clinical attachment level (CAL). At baseline and after 6 months, intrabony defect
      (IBD) fill was radiologically assessed using computer software. RESULTS: Mean PD
      reduction and mean CAL gain were found to be greater in the MF group than the
      placebo group at all visits. Furthermore, a significantly greater mean percentage
      of bone fill was found in the MF group (26.17% +/- 6.66%) than the placebo sites
      (3.75% +/- 8.06%) (P <0.001). CONCLUSION: There was greater decrease in mSBI and
      PD and more CAL gain with significant IBD fill at vertical defect sites treated
      with SRP plus locally delivered MF, versus SRP plus placebo, in smokers with
      generalized CP.

PMID- 23130656
TI  - Photoinduced charge generation in a molecular bulk heterojunction material.
AB  - Understanding the charge generation dynamics in organic photovoltaic bulk
      heterojunction (BHJ) blends is important for providing the necessary guidelines
      to improve overall device efficiency. Despite more than 15 years of experimental
      and theoretical studies, a universal picture describing the generation and
      recombination processes operating in organic photovoltaic devices is still being
      forged. We report here the results of ultrafast transient absorption spectroscopy
      measurements of charge photogeneration and recombination processes in a high
      performing solution-processed molecular BHJ. For comparison, we also studied a
      high-performing polymer-based BHJ material. We find that the majority of charge
      carriers in both systems are generated on <100 fs time scales and posit that
      excited state delocalization is responsible for the ultrafast charge transfer.
      This initial delocalization is consistent with the fundamental uncertainty
      associated with the photon absorption process (in the visible, lambda/4pi > 30
      nm) and is comparable with the phase-separated domain size. In addition, exciton
      diffusion to charge-separating heterojunctions is observed at longer times (1-500
      ps). Finally, charge generation in pure films of the solution processed molecule
      was studied. Polarization anisotropy measurements clearly demonstrate that the
      optical properties are dominated by molecular (Frenkel) exictons and delocalized
      charges are promptly produced (t < 100 fs).

PMID- 23130657
TI  - Stressors of NICU mothers and the effect of counseling-experience from a tertiary
      care teaching hospital, India.
AB  - OBJECTIVE: To determine the effect of counseling on stress levels of NICU
      mothers. METHODS: Stress levels were assessed using the Parental Stressor Scale:
      Neonatal Intensive Care Unit (PSS:NICU) questionnaire among 100 NICU mothers.
      After providing counseling including NICU educational support, the questionnaire
      was re-administered after 48 h. Coding of the responses was done and the data was
      analyzed using SPSS Ver.16. RESULTS: The mean pre intervention subscale stress
      score was highest for parental role alteration (4.12) followed by looks and
      behavior of the baby (4.10) and sights and sounds (2.55). There was significant
      reduction in the post-counseling stress levels among NICU mothers in all three
      sub scales of PSS:NICU. CONCLUSION: Counseling of mothers whose babies are
      admitted to the NICU with regards to various aspects of the infant's environment
      and condition was significantly effective in reducing the stress levels of
      mothers.

PMID- 23130659
TI  - Probing the binding of cationic lipids with dendrimers.
AB  - Polycationic polymers are used extensively in biology to disrupt cell membranes
      and thus enhance the transport of materials into the cell. We report the bindings
      of several lipids cholesterol (Chol), 1,2-dioleoyl-3-trimethylammonium
      propane(DOTAP), dioctadecyldimethylammoniumbromide (DDAB), and
      dioleoylphosphatidylethanolamine (DOPE) to dendrimers of different compositions
      such as mPEG-PAMAM (G3), mPEG-PAMAM (G4), and PAMAM (G4) under physiological
      conditions. FTIR, UV-visible spectroscopic, methods and molecular modeling were
      used to analyze the lipid binding mode, the binding constant, and the effects of
      lipid complexation on the dendrimer structure. The structural analysis showed
      that lipids bind dendrimers through both hydrophilic and hydrophobic contacts
      with overall binding constants of K(chol-mPEG-G3) = 1.7 * 10(3) M(-1), K(chol
      mPEG-PAMAM-G4) = 2.7 * 10(3) M(-1), K(chol-PAMAM-G4) = 1.0 * 10(3) M(-1), K(DOPE
      mPEG-G3) = 1.5 * 10(3) M(-1), K(DOPE-mPEG-PAMAM-G4) = 1.6 * 10(3) M(-1), K(DOPE
      PAMAM-G4) = 5.3 * 10(2) M(-1), K(DDAB-mPEG-G3) = 1.5 * 10(3) M(-1), K(DDAB-mPEG
      PAMAM-G4) = 1.9 * 10(2) M(-1), K(DDAB-PAMAM-G4) = 7.0 * 10(2) M(-1), K(DOTAP-mPEG
      G3) = 1.9 * 10(3) M(-1), K(DOTAP-mPEG-PAMAM-G4) = 1.5 * 10(3) M(-1), and K(DOTAP
      PAMAM-G4) = 5.7 * 10(2) M(-1). Weaker interaction was observed as dendrimer
      cationic charges increased. The free binding energies from docking were -5.15
      (cholesterol), -5.79 (DDAB), and -5.36 kcal/mol (DOTAP) with the order of
      stability DDAB-PAMAM-G-4 > DOTAP-PAMAM-G4 > cholesterol-PAMAM-G4, consistent with
      the spectroscopic results. Dendrimers might act as carriers to transport lipids
      in vitro.

PMID- 23130658
TI  - Efficient delivery of cyclic peptides into mammalian cells with short sequence
      motifs.
AB  - Cyclic peptides hold great potential as therapeutic agents and research tools,
      but their broad application has been limited by poor membrane permeability. Here,
      we report a potentially general approach for intracellular delivery of cyclic
      peptides. Short peptide motifs rich in arginine and hydrophobic residues (e.g.,
      FPhiRRRR, where Phi is l-2-naphthylalanine), when embedded into small- to medium
      sized cyclic peptides (7-13 amino acids), bound to the plasma membrane of
      mammalian cultured cells and were subsequently internalized by the cells.
      Confocal microscopy and a newly developed peptide internalization assay
      demonstrated that cyclic peptides containing these transporter motifs were
      translocated into the cytoplasm and nucleus at efficiencies 2-5-fold higher than
      that of nonaarginine (R(9)). Furthermore, incorporation of the FPhiRRRR motif
      into a cyclic peptide containing a phosphocoumaryl aminopropionic acid (pCAP)
      residue generated a cell permeable, fluorogenic probe for detecting intracellular
      protein tyrosine phosphatase activities.

PMID- 23130660
TI  - Quantitating cell-cell interaction functions with applications to glioblastoma
      multiforme cancer cells.
AB  - We report on a method for quantitating the distance dependence of cell-cell
      interactions. We employ a microchip design that permits a multiplex, quantitative
      protein assay from statistical numbers of cell pairs, as a function of cell
      separation, with a 0.15 nL volume microchamber. We interrogate interactions
      between pairs of model brain cancer cells by assaying for six functional proteins
      associated with PI3k signaling. At short incubation times, cells do not appear to
      influence each other, regardless of cell separation. For 6 h incubation times,
      the cells exert an inhibiting influence on each other at short separations and a
      predominately activating influence at large separation. Protein-specific cell
      cell interaction functions are extracted, and by assuming pairwise additivity of
      those interactions, the functions are shown to correctly predict the results from
      three-cell experiments carried out under the identical conditions.

PMID- 23130661
TI  - Lubiprostone stimulates small intestinal mucin release.
AB  - BACKGROUND: Lubiprostone is a synthetic bicyclic fatty acid derivative of
      prostaglandin E1 (PGE1) used for chronic constipation. The best known action of
      lubiprostone is simulation of Cl- dependent fluid secretion. In a mouse model of
      the genetic disease cystic fibrosis, we previously showed that in vivo
      administration of lubiprostone resulted in greater mucus accumulation in the
      small intestine. The aim of this study was to directly test whether lubiprostone
      stimulates intestinal mucin release. METHODS: Mucin release was measured by
      mounting segments (4-5 cm) of mouse proximal-mid small intestine in an organ
      bath, allowing access to the perfusate (luminal) and the bath (serosal)
      solutions. Nifedipine (10-6 M) and indomethacin (10-5 M) were included in all
      solutions to inhibit smooth muscle activity and endogenous prostaglandin
      production, respectively. The tissue was equilibrated under flow for 30 min,
      using the perfusate collected during the final 10 min of the equilibration period
      to measure unstimulated release rate. Stimulus was then added to either the
      perfusate or the bath and the perfusate was collected for another 30 min to
      measure the stimulated mucin release rate. Mucin in perfusates was quantified by
      periodic acid-Schiff's base dot-blot assay, using purified pig gastric mucin as a
      standard. RESULTS: When applied luminally at 1 MUM lubiprostone was ineffective
      at stimulating mucin release. When added to the serosal solution, 1 MUM
      lubiprostone stimulated mucin release to ~300% of the unstimulated rate. As a
      positive control, serosal 1 MUM prostaglandin E2 increased mucin release to ~400%
      of the unstimulated rate. CONCLUSIONS: These results support the idea that
      lubiprostone has prostaglandin-like actions on the intestine, which includes
      stimulation of mucin release. Stimulation of mucin release by lubiprostone may be
      protective in gastrointestinal conditions where loss of mucus is believed to
      contribute to pathogenesis. Thus, in addition to chronic constipation, there is
      greater potential for the therapeutic applications of lubiprostone.

PMID- 23130662
TI  - Glycolytic enzymes PGK1 and PKM2 as novel transcriptional targets of PPARgamma in
      breast cancer pathophysiology.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear
      receptor and plays important roles in breast cancer cell proliferation. The
      complexity of the underlying biochemical and molecular mechanisms of breast
      cancer and the involvement of PPARgamma in breast cancer pathophysiology are
      unclear. In this study, we carried out prediction of the peroxisome proliferator
      response element (PPRE) motifs in 2332 genes reported to be involved in breast
      cancer in literature. A total of 178 genes were found to have PPRE (DR1/DR2)
      and/or PPAR-associated conserved motif (PACM) motifs. We further constructed
      protein-protein interaction network, disease gene network and gene ontology (GO)
      analyses to identify novel key genes for experimental validation. We identified
      two genes in the glycolytic pathway (phosphoglycerate kinase 1 (PGK1) and
      pyruvate kinase M2 (PKM2)) at the ATP production steps and experimentally
      validated their repression by PPARgamma in two breast cancer cell lines MDA-MB
      231 and MCF-7. Further analysis suggested that this repression leads to decrease
      in ATP levels and apoptosis. These investigations will help us in understanding
      the molecular mechanisms by which PPARgamma regulates the cellular energy pathway
      and the use of its ligands in human breast cancer therapeutics.

PMID- 23130663
TI  - Aminoalkoxysilane reactivity in surface amine gradients prepared by controlled
      rate infusion.
AB  - The reactivity of a series of substituted aminoalkoxysilanes for surface amine
      gradient formation has been studied using a newly developed time-based exposure
      method termed controlled-rate infusion (CRI). The aminoalkoxysilanes used include
      those that contain primary, secondary, and tertiary monoamines as well as more
      than one amine group (diamine and triamine). X-ray photoelectron spectroscopy
      (XPS) was used to confirm the presence of a gradient in each case and to acquire
      detailed information on gradient composition from which kinetic data were
      obtained. The total area under the N 1s XPS spectra allows for the extent of
      amine modification to be quantitatively assessed along each gradient. The N 1s
      peaks actually appear as doublets, providing additional data on the level of
      protonation and, hence, amine basicity on the dry surface. The degree of
      protonation showed an interesting trend toward smaller values running from top to
      bottom along gradients incorporating the most basic amines. The gradient
      profiles, including initial steepness and extent of saturation, were shown to be
      highly dependent on the aminoalkoxysilane precursor employed. The highest levels
      of modification were achieved for the diamine and primary monoamine precursors
      while the more hindered amines produced lower levels of surface modification and
      took longer for saturation to be achieved. By fitting the gradient data to a
      simple first-order kinetic model, rate constants for the condensation reaction
      between each aminosilane and accessible surface silanol groups were obtained. The
      rate constants follow the trend: triamine ~ diamine > monoamine and primary >
      secondary > tertiary, indicating kinetic factors also play an important role in
      controlling surface modification. The presence of more than one amine group on
      the silane is concluded to enhance the rate of condensation to the surface
      silanol groups, while the more hindered secondary and tertiary amines slow
      condensation. Collectively, the results provide valuable new data on how the
      number of amine groups, degree of substitution, and steric hindrance influence
      silane reactivity with silica surfaces, amine surface coverage, and basicity
      along the gradient profile.

PMID- 23130664
TI  - Duration until nighttime blood pressure fall indicates excess sodium retention.
AB  - Impaired renal sodium excretion causes sodium retention, which prevents the
      nocturnal dip in blood pressure (BP); thus, high BP persists until excess sodium
      is excreted. The authors defined "dipping time" (DT) as the duration until the
      nocturnal BP falls below 90% of the daytime average. Diuretic (e.g.,
      hydrochlorothiazide [HCTZ]) and angiotensin receptor blocker (ARB) are able to
      eliminate sodium retention and restore the non-dipper BP rhythm. Reanalysis of
      two previous studies demonstrate that HCTZ and ARB shortened the DT. Shortening
      DT correlated directly with the increase in daytime urinary sodium excretion
      (Study 2). DT can be used as a preliminary indicator of sodium retention.

PMID- 23130665
TI  - One versus many: capturing the use of multiple emotion regulation strategies in
      response to an emotion-eliciting stimulus.
AB  - The past decade and a half has witnessed a renewed interest in the study of
      affective processes. James Gross' process model of emotion regulation has
      provided a theoretical framework for this approach. This model stipulates that
      individuals have a repertoire of emotion regulation strategies they use in order
      to modify their affect and/or the situations eliciting such affect. However,
      empirical investigations of the use of emotion regulation strategies have largely
      oversimplified this model by assuming that individuals use only one regulation
      strategy to manage the affect elicited by a given emotion-eliciting stimulus or
      situation. This is problematic because it has resulted in a limited understanding
      of the complex process by which individuals select and implement regulation
      strategies. In this brief report, we present findings suggesting that people
      spontaneously use multiple emotion regulation strategies in response to a brief
      disgust-eliciting film clip. We discuss implications for future empirical work on
      emotion regulation strategies.

PMID- 23130666
TI  - Direct genetic evidence for reproductive philopatry and associated fine-scale
      migrations in female blacktip reef sharks (Carcharhinus melanopterus) in French
      Polynesia.
AB  - Conservation of top predators has been emphasized as essential in an ecosystem
      due to their role in trophic chain regulation. Optimizing conservation strategies
      for these endangered marine top predators requires direct estimates of breeding
      patterns and connectivity as these are essential to understanding the population
      dynamics. There have been some attempts to investigate breeding patterns of reef
      sharks from litter reconstruction using molecular analyses. However, direct fine
      scale migrations of female sharks for parturition as well as connectivity at a
      medium scale like between islands remain mostly unknown. We used microsatellite
      DNA markers and a likelihood-based parentage analysis to determine breeding
      patterns of female blacktip reef sharks in Moorea (Society Islands, French
      Polynesia). Most females gave birth at their home island but some migrated to
      specific nursery areas outside the area they are attached to, sometimes going to
      another island 50 km away across deep ocean. Our analysis also revealed that
      females migrated to the same nursery for every birthing event. Many offspring
      showed a high level of inbreeding indicating an overall reduced population size,
      restricted movements and dispersal, or specific mating behaviour. Females
      represent the vectors that transport the genes at nursery grounds, and their
      fidelity should thus define reproductive units. As females seem to be
      philopatric, males could be the ones dispersing genes between populations. These
      results highlight the need to conserve coastal zones where female reef sharks
      seem to exhibit philopatry during the breeding season.

PMID- 23130669
TI  - Unresolved issues in transcatheter atrial fibrillation ablation: silent
      cerebrovascular ischemias.

PMID- 23130670
TI  - Thermally programmable pH buffers.
AB  - Many reactions in both chemistry and biology rely on the ability to precisely
      control and fix the solution concentrations of either protons or hydroxide ions.
      In this report, we describe the behavior of thermally programmable pH buffer
      systems based on the copolymerization of varying amounts of acrylic acid (AA)
      groups into N-isopropylacrylamide polymers. Because the copolymers undergo phase
      transitions upon heating and cooling, the local environment around the AA groups
      can be reversibly switched between hydrophobic and hydrophilic states affecting
      the ionization behavior of the acids. Results show that moderate temperature
      variations can be used to change the solution pH by two units. However, results
      also indicate that the nature of the transition and its impact on the pH values
      are highly dependent on the AA content and the degree of neutralization.

PMID- 23130671
TI  - Comparison of photo-oxidation reactions in batch and a new photosensitizer
      immobilized microfluidic device.
AB  - A glass microfluidic device has been functionalized with photoactive porphyrins
      for performing reactions which are mediated by singlet molecular oxygen. The
      resulting device was used to investigate the photochemical oxidation of
      cholesterol, alpha-terpinene, and citronellol under flow conditions, and the
      results were compared with similar batch reactions.

PMID- 23130672
TI  - EGLN1 variants influence expression and SaO2 levels to associate with high
      altitude pulmonary oedema and adaptation.
AB  - EGLN1 [encoding HIF (hypoxia-inducible factor)-prolyl hydroxylase 2] plays a
      pivotal role in the HIF pathway and has emerged as one of the most intriguing
      genes with respect to physiology at HA (high altitude). EGLN1, being an actual
      oxygen sensor, appears to have a potential role in the functional adaptation to
      the hypobaric hypoxic environment. In the present study, we screened 30
      polymorphisms of EGLN1, evaluated its gene expression and performed association
      analyses. In addition, the role of allelic variants in altering TF (transcription
      factor)-binding sites and consequently the replacement of TFs at these loci was
      also investigated. The study was performed in 250 HAPE-p [HAPE (HA pulmonary
      oedema)-patients], 210 HAPE-f (HAPE-free controls) and 430 HLs (healthy Ladakhi
      highland natives). The genotypes of seven polymorphisms, rs1538664, rs479200,
      rs2486729, rs2790879, rs480902, rs2486736 and rs973252, differed significantly
      between HAPE-p and HAPE-f (P<0.008). The genotypes AA, TT, AA, GG, CC, AA and GG
      of rs1538664, rs479200, rs2486729, rs2790879, rs480902, rs2486736 and rs973252,
      prevalent in HAPE-p, were identified as risk genotypes and their counterpart
      homozygotes, prevalent in HLs, were identified as protective. EGLN1 expression
      was up-regulated 4.56-fold in HAPE-p (P=0.0084). The risk genotypes, their
      haplotypes and interacting genotypes were associated with up-regulated EGLN1
      expression (P<0.05). Similarly, regression analysis showed that the risk alleles
      and susceptible haplotypes were associated with decreased SaO2 (arterial oxygen
      saturation) levels in the three groups. The significant inverse correlation of
      SaO2 levels with PASP (pulmonary artery systolic pressure) and EGLN1 expression
      and the association of these polymorphisms with SaO2 levels and EGLN1 expression
      contributed to uncovering the molecular mechanism underlying hypobaric hypoxic
      adaptation and maladaptation.

PMID- 23130673
TI  - Capillary viscometer for fully automated measurement of the concentration and
      shear dependence of the viscosity of macromolecular solutions.
AB  - The construction and operation of a novel viscometer/rheometer are described. The
      instrument is designed to measure the viscosity of a macromolecular solution
      while automatically varying both solute concentration and shear rate. Viscosity
      is calculated directly from Poiseuille's law, given the measured difference in
      pressure between two ends of a capillary tube through which the solution is
      flowing at a known rate. The instrument requires as little as 0.75 mL of a
      solution to provide a full profile of viscosity as a function of concentration
      and shear rate, and it can measure viscosities as high as 500 cP and as low as 1
      cP, at shear rates between 10 and 2 * 10(3) s(-1). The results of control
      experiments are presented to document the accuracy and precision of measurement
      at both low and high concentration of synthetic polymers and proteins.

PMID- 23130674
TI  - Early experience with single-incision laparoscopic surgery for the placement of a
      gastrostomy in a 10-year-old girl: a case report.
AB  - INTRODUCTION: Access procedures for alimentation have been performed both
      endoscopically and surgically. In patients in whom endoscopic gastrostomy feeding
      tubes cannot be placed, single-incision laparoscopic surgery gastrostomy is an
      alternative method. This minimally invasive approach is a new technique performed
      through a single umbilical incision and without the need for additional
      laparoscopic ports. CASE PRESENTATION: In this article we present a case of
      single-incision laparoscopic surgery gastrostomy performed with conventional
      laparoscopic instruments in a 10-year-old girl of Caucasian ethnicity who was not
      a candidate for a percutaneous endoscopic gastrostomy tube because of esophageal
      varices due to her advanced-stage cystic fibrosis with liver cirrhosis and portal
      hypertension. She also had an umbilical hernia, which was repaired during the
      same procedure through the same incision. Access and pneumoperitoneum were
      obtained through the umbilicus with the single-incision laparoscopic surgery
      port. The selected site for the feeding tube in the stomach was exteriorized
      through this incision and a feeding tube was placed. The stomach was returned
      into the abdomen. The fascial defect, and thus also the hernia, was repaired, and
      the 2cm umbilical incision was closed with endocutaneous sutures. The total
      operative time was 25 minutes. Our patient's intra-operative and post-operative
      course was uneventful. We were able to use the feeding tube on the first post
      operative day with good intestinal function. Our patient and her parents were
      pleased with the cosmetic result. CONCLUSIONS: The single-incision laparoscopic
      surgery procedure seems to be a less invasive alternative to open placement of
      gastrostomy. This approach has the possible advantages of reduced post-operative
      pain, faster return to normal function, reduced port site complications, improved
      cosmesis and better patient satisfaction.

PMID- 23130675
TI  - Toward personalized sexual medicine (part 3): testosterone combined with a
      Serotonin1A receptor agonist increases sexual satisfaction in women with HSDD and
      FSAD, and dysfunctional activation of sexual inhibitory mechanisms.
AB  - INTRODUCTION: Among other causes, low sexual desire in women may result from
      dysfunctional activation of sexual inhibition mechanisms during exposure to sex.
      Administration of sublingual 0.5 mg testosterone (T) increases the sensitivity of
      the brain to sexual cues, which might amplify sexual inhibitory mechanisms
      further in women already prone to sexual inhibition. Sexual stimulation might
      elicit a prefrontal cortex (PFC)-mediated phasic increase in sexual inhibition,
      in which activity of 5-hydroxytryptamine (5-HT, serotonin) is involved. A single
      dose of 5-HT receptor agonist (5-HT(1A)ra) might reduce the sexual stimulation
      induced PFC-mediated sexual inhibition during a short period after
      administration. Consequently, treatment with a single dose of T+5-HT(1A)ra might
      enhance sexual responsiveness, particularly in women exhibiting sexual
      inhibition. AIM: To investigate if treatment with a single dosage of T+5-HT(1A)ra
      will produce improvement in sexual functioning in women with Hypoactive Sexual
      Desire Disorder (HSDD) as the result of dysfunctional high sexual inhibition.
      METHODS: Fifty-four women were divided on the basis of their excitatory or
      inhibitory responses during T+phosphodiesterase type 5 inhibitor (PDE5i) in low
      (N = 26) and high inhibitors (N = 28). Physiological and subjective indices of
      sexual functioning were measured in a participant-controlled ambulatory
      psychophysiological experiment at home (the first week of each drug treatment).
      In a bedroom experiment (the subsequent 3 weeks), sexual functioning was
      evaluated by event, week, and monthly diaries. MAIN OUTCOME MEASURES: Subjective:
      sexual satisfaction, experienced genital arousal, sexual desire. Physiological:
      vaginal pulse amplitude. RESULTS: Women with high inhibition show a marked
      improvement in sexual function in response to treatment with T+5-HT ra relative
      to placebo and relative to T+PDE5i. CONCLUSIONS: The present study demonstrated
      that on-demand T+5-HT ra is a potentially promising treatment for women with
      HSDD, particularly for those women who are prone to sexual inhibition.

PMID- 23130676
TI  - Analysis of urological procedures in men who died from prostate cancer using a
      population-based approach.
AB  - What's known on the subject? and What does the study add? Very few studies have
      examined end-of-life urological studies in men with prostate cancer. These
      studies reported fewer procedures in men who received primary therapy for
      prostate cancer. However, these studies were typically single institution or had
      a short follow-up period. The present study is the first population-based study
      examining end-of-life urological procedures and uses a geographic region
      encompassing 385 000 patients. Furthermore, this study incorporates both hospital
      and office-based procedures. This approach has not been previously undertaken.
      OBJECTIVE: To determine using a population-based approach whether men with end
      stage prostate cancer who had definitive primary therapy might require fewer
      urological interventions. Repeated urological procedures can impact health
      related quality of life in patients dying from prostate cancer. PATIENTS AND
      METHODS: Using the Marshfield Epidemiological Study Area (MESA) database and
      tumour registry, we compared end-of-life interventions in men who died from
      prostate cancer between 1991 and 2009. Patient charts were queried for urological
      procedures using International Classification of Disease Modification, 9th
      edition (ICD9) codes for 3 years before death. Clinicopathological information
      was examined including whether the patient had a history of primary therapy
      (radiation or radical prostatectomy). RESULTS: Among 280 patients dying from
      prostate cancer, 52 (19%) required 153 urological procedures during the last 3
      years of life. The frequency of procedures increased closer to death. The most
      common procedures involved nephrostomy tube (56%), Foley catheter (24%) and
      transurethral resection of the prostate (10%). Clinicopathological features did
      not predict the need for an end-of-life urological procedure. There was no
      difference in the frequency of upper or lower tract procedures in surgery or
      radiation patients compared with patients without primary therapy (P = 0.556 and
      P = 0.508). Using a Kaplan-Meier analysis, there were no differences between
      groups in the proportion of patients not requiring a procedure (n = 280; P =
      0.179). CONCLUSIONS: This is the first population-based study to examine the
      frequency of urological procedures in patients with end-stage prostate cancer. A
      minority of patients (19%) required urological procedures during the final 3
      years of life. A history of surgery or radiation did not influence the overall
      risk for urological intervention.

PMID- 23130678
TI  - The effect of standard compared to enhanced instruction and verbal feedback on
      anorectal manometry measurements.
AB  - BACKGROUND: Guidelines recommend instruction and motivation during anorectal
      manometry; however, its impact on findings has not been reported. This study
      assessed the effects of standard versus enhanced instruction and verbal feedback
      on the results of anorectal manometry. METHODS: High-resolution manometry was
      performed by a solid-state catheter with 10 circumferential sensors at 6 mm
      separation across the anal canal and two rectal sensors. Measurements were
      acquired first with standard instruction and then with enhanced instruction and
      verbal feedback. On both occasions, squeeze pressure and duration during three
      voluntary contractions and intra-rectal pressure and recto-anal pressure gradient
      (RAPG) during three attempts at simulated defecation were assessed. KEY RESULTS:
      A total of 70 consecutive patients (54 female; age 25-82 years) referred for
      investigation of fecal incontinence (n = 31), constipation, and related disorders
      of defecation (n = 39) were studied. Enhanced instruction and verbal feedback
      increased maximum squeeze pressure (Delta10 +/- 28.5 mmHg; P < 0.0038) and
      duration of contraction (Delta3 +/- 4 s; P < 0.0001). During simulated
      defecation, it increased intra-rectal pressure (Delta12 +/- 14 mmHg; P < 0.003)
      and RAPG (Delta11 +/- 20 mmHg; P < 0.0001). Using standard diagnostic criteria,
      the intervention changed manometric findings from locally validated 'pathologic'
      to 'normal' values in 14/31 patients with incontinence and 12/39 with disorders
      of defecation. CONCLUSIONS & INFERENCES: Enhanced instruction and verbal feedback
      significantly improved voluntary anorectal functions and resulted in a clinically
      relevant change of manometric diagnosis in some patients. Effective explanation
      of procedures and motivation during manometry is required to ensure consistent
      results and to provide an accurate representation of patient ability to retain
      continence and evacuate stool.

PMID- 23130679
TI  - Hazard identification of powder generated from a chemical vapor deposition
      process in the semiconductor manufacturing industry.

PMID- 23130680
TI  - Morphologic, flow cytometric, functional, and molecular analyses of S100B
      positive lymphocytes, unique cytotoxic lymphocytes containing S100B protein.
AB  - Little is known about the S100B+ lymphocytes, which are unique human peripheral
      blood lymphocytes (PBL) containing the S100B protein. It has recently been shown
      that S100B is released from various types of S100B+ cells and exhibits varied
      cytokine-like activities. In this study, we precisely characterized the S100B+
      lymphocytes of healthy adults with respect to the proportion in the whole PBL,
      immunophenotypes, function, and their S100B mRNA expression and also evaluated
      their S100B-releasing activity upon stimulation. S100B+ lymphocytes were detected
      in all individuals examined, and the proportion of S100B+ lymphocytes in the
      whole PBL ranged from 0.42% to 16.15% (mean, 4.21%). In addition, two subtypes of
      S100B + lymphocytes, a CTL subtype (CD3+ CD8+ CD16-) and a NK subtype (CD3- CD3-
      CD16+), were detected. The majority of the CTL subtype of S100B+ lymphocytes
      expressed the alphabeta-T-cell receptor. Surprisingly, S100B mRNA was detected
      not only in S100B+ lymphocytes, but also in every S100B+ lymphocytes, although
      the expression levels of S100B mRNA in S100B- lymphocytes were much lower than
      those of S100B+ lymphocytes. The CTL subtype of S100B+ lymphocytes exhibited
      blastic morphological changes, proliferated and released S100B upon stimulation
      with phytohemagglutinin. The NK subtype of S100B+ lymphocytes exhibited
      morphological NK activity when cocultivated with NK-sensitive target, K-562
      cells. Thus, the CTL subtype of S100B+ lymphocytes exhibit the biological
      characteristics of T cells, while the NK subtype of S100B+ lymphocytes exhibit
      the characteristics of NK cells. These results suggest that S100B+ lymphocytes
      are a particular subtype of cytotoxic lymphocytes that play a unique role in
      antitumor immunity.

PMID- 23130681
TI  - Effective panchromatic sensitization of electrochemical solar cells: strategy and
      organizational rules for spatial separation of complementary light harvesters on
      high-area photoelectrodes.
AB  - Dye-sensitized solar cells, especially those comprising molecular chromophores
      and inorganic titania, have shown promise as an alternative to silicon for
      photovoltaic light-to-electrical energy conversion. Co-sensitization (the use of
      two or more chromophores having complementary absorption spectra) has attracted
      attention as a method for harvesting photons over a broad spectral range. If
      implemented successfully, then cosensitization can substantially enhance
      photocurrent densities and light-to-electrical energy conversion efficiencies. In
      only a few cases, however, have significant overall improvements been obtained.
      In most other cases, inefficiencies arise due to unconstructive energy or charge
      transfer between chromophores or, as we show here, because of modulation of
      charge-recombination behavior. Spatial isolation of differing chromophores offers
      a solution. We report a new and versatile method for fabricating two-color
      photoanodes featuring spatially isolated chromophore types that are selectively
      positioned in desired zones. Exploiting this methodology, we find that
      photocurrent densities depend on both the relative and absolute positions of
      chromophores and on "local" effective electron collection lengths. One version of
      the two-color photoanode, based on an organic push-pull dye together with a
      porphyrin dye, yielded high photocurrent densities (J(SC) = 14.6 mA cm(-2)) and
      double the efficiency of randomly mixed dyes, once the dyes were optimally
      positioned with respect to each other. We believe that the organizational rules
      and fabrication strategy will prove transferrable, thereby advancing
      understanding of panchromatic sensitization as well as yielding higher efficiency
      devices.

PMID- 23130682
TI  - Tuning the electronic properties of nonplanar exTTF-based push-pull chromophores
      by aryl substitution.
AB  - A new family of pi-extended tetrathiafulvalene (exTTF) donor-acceptor
      chromophores has been synthesized by [2 + 2] cycloaddition of TCNE with exTTF
      substituted alkynes and subsequent cycloreversion. X-ray data and theoretical
      calculations, performed at the B3LYP/6-31G** level, show that the new
      chromophores exhibit highly distorted nonplanar molecular structures with largely
      twisted 1,1,4,4-tetracyanobuta-1,3-diene (TCBD) units. The electronic and optical
      properties, investigated by UV/vis spectroscopy and electrochemical measurements,
      are significantly modified when the TCBD acceptor unit is substituted with a
      donor phenyl group, which increases the twisting of the TCBD units and reduces
      the conjugation between the two dicyanovinyl subunits. The introduction of phenyl
      substituents hampers the oxidation and reduction processes and, at the same time,
      largely increases the optical band gap. An effective electronic communication
      between the donor and acceptor units, although limited by the distorted molecular
      geometry, is evidenced both in the ground and in the excited electronic states.
      The electronic absorption spectra are characterized by low- to medium-intense
      charge-transfer bands that extend to the near-infrared.

PMID- 23130683
TI  - Cesarean delivery in obese women: a comprehensive review.
AB  - BACKGROUND: Obesity (BMI >=30) is a significant independent risk factor for many
      gestational complications, including cesarean delivery (CD). While CD rates are
      increasing in women of every BMI, the trend is more pronounced as maternal weight
      increases. OBJECTIVE: This review seeks to describe the risk modulators that
      explain the high prevalence of CD in obese women, as well as to discuss the
      excess complications of the procedure in this group of parturients. In assessing
      the rationale for the procedure and weighing this against the excess risks
      involved, a clearer indication of when to perform CD in obese women might be
      developed. RESULTS: A thorough review of the literature indicates that a
      decreased cervical dilation rate, an increased induction rate, the presence of
      comorbid conditions, concern about shoulder dystocia, and weight gain in excess
      of recommendations during pregnancy all may contribute to the high rate of CD in
      obese women. Obese women are at increased risk of CD-related complications
      including anesthetic complications, wound complications, venous thromboembolism
      (VTE), and failure of vaginal birth after CD. CONCLUSIONS: Given the excess risks
      associated with CD in obese women, and that some of the rationale for the
      procedure (e.g. slower labor, concern about shoulder dystocia) may not be
      justified based on current evidence, a reassessment of the threshold at which
      obese women are recommended for CD is necessary.

PMID- 23130684
TI  - The interaction between maternal stress and the ontogeny of the innate immune
      system during teleost embryogenesis: implications for aquaculture practice.
AB  - The barrier defences and acellular innate immune proteins play critical roles
      during the early-stage fish embryos prior to the development of functional organ
      systems. The innate immune proteins in the yolk of embryos are of maternal
      origin. Maternal stress affects the maternal-to-embryo transfer of these proteins
      and, therefore, environmental stressors may change the course of embryo
      development, including embryonic immunocompetency, via their deleterious effect
      on maternal physiology. This review focuses on the associations that exist
      between maternal stress, maternal endocrine disturbance and the responses of the
      acellular innate immune proteins of early-stage fish embryos. Early-stage
      teleostean embryos are dependent upon the adult female for the formation of the
      zona pellucida as an essential barrier defence, for their supply of nutrients,
      and for the innate immunity proteins and antibodies that are transferred from the
      maternal circulation to the oocytes; maternally derived hormones are also
      transferred, some of which (such as cortisol) are known to exert a suppressive
      action on some aspects of the immune defences. This review summarizes what is
      known about the effects of oocyte cortisol content on the immune system
      components in early embryos. The review also examines recent evidence that
      embryonic cells during early cleavage have the capacity to respond to increased
      maternal cortisol transfer; this emphasizes the importance of maternal and early
      immune competence on the later life of fishes, both in the wild and in intensive
      culture.

PMID- 23130685
TI  - Stock-specific variation of trophic position, diet and environmental stress
      markers in Atlantic salmon Salmo salar during feeding migrations in the Baltic
      Sea.
AB  - This study investigated stock-specific variation in selected ecophysiological
      variables during the feeding migrations of Atlantic salmon Salmo salar in the
      Baltic Sea. Oxidative stress biomarkers and EROD (ethoxyresorufin-O-deethylase,
      Cyp1A enzyme) activity were used as indicators of possible environmental stress
      and stable isotopes as determinants of diet and trophic position. Latvian S.
      salar stocks Daugava and Gauja had distinct stable-isotope signatures compared to
      the other stocks, indicating differences in migration patterns, residency or
      arrival times, or dietary specialization among stocks. Salmo salar originating
      from Daugava and Gauja also had lower catalase enzyme activity than the other
      stocks. Post-smolts originating from rivers of the Gulf of Finland had elevated
      EROD activities compared to fish of the same age from Bothnian Bay rivers, which
      could indicate exposure to organochlorine pollutants. No other stock-specific
      differences in oxidative stress biomarkers were found. The study demonstrates how
      genetic, oxidative stress biomarker, EROD and stable-isotope data may be combined
      to study trophic position, prey prevalence and environmental stress of mixed S.
      salar stocks foraging in the sea.

PMID- 23130686
TI  - Reproductive biology and spatiotemporal patterns of spawning in striped marlin
      Kajikia audax.
AB  - This study presents the first histology-based assessment of the reproductive
      dynamics of south-west Pacific striped marlin Kajikia audax. Maturity and
      reproductive status were assessed from histological sections of ovaries (n = 234)
      and testes (n = 243) of fish caught in commercial longline and recreational
      fisheries between 2006 and 2009. Spawning peaked in the Coral Sea during November
      and December at sea surface temperatures between 24.8 and 28.3 degrees  C. Lower
      jaw fork length (L(LJF)) at 50% maturity (L(LJF50)), a key variable for stock
      assessment, was estimated to be 2100 +/- 102 mm (mean + s.e.) for females and
      1668 +/- 18 mm for males. Unlike large pelagic tunas Thunnus spp., the proportion
      of females increased with length and spawning fish formed multiple large-scale
      aggregations within a broad latitudinal band. This study provides a starting
      point for biological parameters needed for stock assessment and conservation of
      K. audax and introduces the multiple aggregation spawning concept as a
      reproductive mechanism to explain genetic heterogeneity observed in some highly
      migratory species.

PMID- 23130687
TI  - The utility of a long-term acoustic recording system for detecting white seabass
      Atractoscion nobilis spawning sounds.
AB  - This study reports the use of a long-term acoustic recording system (LARS) to
      remotely monitor white seabass Atractoscion nobilis spawning sounds at three
      sites along the southern California coastline, adjacent to Camp Pendleton. On the
      basis of previous studies of A. nobilis sound production relative to periods of
      known spawning activity, LARS were set to continuously record ambient sounds for
      a 2 h period around sunset from April to June 2009. Acoustic analyses identified
      A. nobilis courtship sounds on 89, 28 and 45% of the days at the three locations,
      respectively. From 474 h of acoustic data, spawning-related sounds (chants) were
      detected on 19 occasions in 2009 with an additional 11 spawning chants recorded
      during a 2007 validation period. Most spawning chants occurred within 30 min of
      sunset during the months of May and June at a mean +/-S.D. surface temperature of
      18.2 +/- 1.2 degrees  C. Consecutive daily spawning activity was not apparent at
      any sites in 2009. Atractoscion nobilis spawning chants were recorded at all
      three sites, suggesting that shallow rocky reefs which support kelp forests
      provide suitable A. nobilis spawning habitat. Results confirm the utility of
      passive acoustic recorders for identifying A. nobilis spawning periods and
      locations.

PMID- 23130688
TI  - Does the trace element composition of brown trout Salmo trutta eggs remain
      unchanged in spawning redds?
AB  - The temporal stability of trace element concentrations in fertilized,
      artificially incubated anadromous brown trout Salmo trutta eggs and newly hatched
      fry was investigated. The anadromous status of the parental fish was confirmed
      using strontium isotopic analysis of otoliths. Whilst manganese concentrations in
      eggs varied over time, concentrations of aluminium, potassium, magnesium,
      strontium, barium and calcium were all unchanged 1 week and 6 weeks post
      fertilization as well as in recently hatched larvae. The results clearly suggest
      that the distinctive trace element signature present in the eggs and newly
      hatched larvae of anadromous S. trutta (typically characterized by high
      strontium, low barium) is stable over time. Therefore analysis of the trace
      element composition of eggs is concluded to be a cost-effective and reliable
      method for determining the spatial and temporal extent of upstream spawning
      migration by anadromous salmonids. The temporal variability of at least one
      element in this study suggests the stability of untested multi-element signatures
      cannot automatically be assumed.

PMID- 23130689
TI  - Compensatory growth in juvenile roach Rutilus caspicus: effect of starvation and
      re-feeding on growth and digestive surface area.
AB  - The aim of this study was to investigate compensatory growth in juvenile Rutilus
      caspicus during starvation and re-feeding periods. The results confirmed the
      existence of compensatory growth in R. caspicus which depended on the duration of
      food deprivation. Complete compensatory growth occurred in the fish that were
      food deprived for at least 3 weeks. Starvation and re-feeding had no significant
      effect on the digestive somatic index and intestinal surface areas in the fish
      that were food deprived for 1 week, while they showed a significant decrease and
      increase, during starvation and re-feeding in the fish that were food deprived
      for 2 and 3 weeks. This knowledge may have application in aquaculture, as
      appropriate exploitation of compensatory growth can give increased growth rate
      and feeding efficiency.

PMID- 23130690
TI  - Genetic diversity, endemism and phylogeny of lampreys within the genus Lampetra
      sensu stricto (Petromyzontiformes: Petromyzontidae) in western North America.
AB  - Phylogenetic structure of four Lampetra species from the Pacific drainage of
      North America (western brook lamprey Lampetra richardsoni, Pacific brook lamprey
      Lampetra pacifica, river lamprey Lampetra ayresii and Kern brook lamprey Lampetra
      hubbsi) and unidentified Lampetra specimens (referred to as Lampetra sp.) from 36
      locations was estimated using the mitochondrial cytochrome b gene. Maximum
      parsimony and Bayesian inferences did not correspond with any taxonomic scheme
      proposed to date. Rather, although L. richardsoni (from Alaska to California) and
      L. ayresii (from British Columbia to California) together constituted a well
      supported clade distinct from several genetically divergent Lampetra populations
      in Oregon and California, these two species were not reciprocally monophyletic.
      The genetically divergent populations included L. pacifica (from the Columbia
      River basin) and L. hubbsi (from the Kern River basin) and four Lampetra sp.
      populations in Oregon (Siuslaw River and Fourmile Creek) and California (Kelsey
      and Mark West Creeks). These four Lampetra sp. populations showed genetic
      divergence between 2.3 and 5.7% from any known species (and up to 8.0% from each
      other), and may represent morphologically cryptic and thus previously undescribed
      species. A fifth population (from Paynes Creek, California) may represent a range
      extension of L. hubbsi into the Upper Sacramento River.

PMID- 23130691
TI  - Morphological variation between non-native lake- and stream-dwelling pumpkinseed
      Lepomis gibbosusin the Iberian Peninsula.
AB  - The objective of this study was to test if morphological differences in
      pumpkinseed Lepomis gibbosus found in their native range (eastern North America)
      that are linked to feeding regime, competition with other species, hydrodynamic
      forces and habitat were also found among stream- and lake- or reservoir-dwelling
      fish in Iberian systems. The species has been introduced into these systems,
      expanding its range, and is presumably well adapted to freshwater Iberian
      Peninsula ecosystems. The results show a consistent pattern for size of lateral
      fins, with L. gibbosus that inhabit streams in the Iberian Peninsula having
      longer lateral fins than those inhabiting reservoirs or lakes. Differences in fin
      placement, body depth and caudal peduncle dimensions do not differentiate
      populations of L. gibbosus from lentic and lotic water bodies and, therefore, are
      not consistent with functional expectations. Lepomis gibbosus from lotic and
      lentic habitats also do not show a consistent pattern of internal morphological
      differentiation, probably due to the lack of lotic-lentic differences in prey
      type. Overall, the univariate and multivariate analyses show that most of the
      external and internal morphological characters that vary among populations do not
      differentiate lotic from lentic Iberian populations. The lack of expected
      differences may be a consequence of the high seasonal flow variation in
      Mediterranean streams, and the resultant low- or no-flow conditions during
      periods of summer drought.

PMID- 23130692
TI  - Do the maximum sizes, ages and patterns of growth of three reef-dwelling labrid
      species at two latitudes differ in a manner conforming to the metabolic theory of
      ecology?
AB  - The size and age data and patterns of growth of three abundant, reef-dwelling and
      protogynous labrid species (Coris auricularis, Notolabrus parilus and
      Ophthalmolepis lineolata) in waters off Perth at c. 32 degrees  S and in the
      warmer waters of the Jurien Bay Marine Park (JBMP) at c. 30 degrees  S on the
      lower west coast of Australia are compared. Using data for the top 10% of values
      and a randomization procedure, the maximum total length (L(T) ) and mass of each
      species and the maximum age of the first two species were estimated to be
      significantly greater off Perth than in the JBMP (all P < 0.001) and the maximum
      ages of O. lineolata in the two localities did not differ significantly (P >
      0.05). These latitudinal trends, thus, typically conform to those frequently
      exhibited by fish species and the predictions of the metabolic theory of ecology
      (MTE). While, in terms of mass, the instantaneous growth rates of each species
      were similar at both latitudes during early life, they were greater at the higher
      latitude throughout the remainder and thus much of life, which is broadly
      consistent with the MTE. When expressed in terms of L(T), however, instantaneous
      growth rates did not exhibit consistent latitudinal trends across all three
      species. The above trends with mass, together with those for reproductive
      variables, demonstrate that a greater amount of energy is directed into somatic
      growth and gonadal development by each of these species at the higher latitude.
      The consistency of the direction of the latitudinal trends for maximum body size
      and age and pattern of growth across all three species implies that each species
      is responding in a similar manner to differences between the environmental
      characteristics, such as temperature, at those two latitudes. The individual
      maximum L(T), mass and age and pattern of growth of O. lineolata at a higher and
      thus cooler latitude on the eastern Australian coast are consistent with the
      latitudinal trends exhibited by those characteristics for this species in the two
      western Australian localities. The implications of using mass rather than length
      as the indicator variable when comparing the maximum sizes of the three species
      and the trends exhibited by the instantaneous growth rates of those species at
      different latitudes are explored. Although growth curves fitted to both the L(T)
      and masses at age for the males of each species lay above those for their
      females, this would not have influenced the conclusions drawn from common curves
      for both sexes.

PMID- 23130693
TI  - Genetic diversity shaped by historical and recent factors in the live-bearing
      twoline skiffia Neotoca bilineata.
AB  - The endangered twoline skiffia Neotoca bilineata, a viviparous fish of the
      subfamily Goodeinae, endemic to central Mexico (inhabiting two basins, Cuitzeo
      and Lerma-Santiago) was evaluated using genetic and habitat information. The
      genetic variation of all remaining populations of the species was analysed using
      both mitochondrial and microsatellite markers and their habitat conditions were
      assessed using a water quality index (I(WQ)). An 80% local extinction was found
      across the distribution of N. bilineata. The species was found in three of the 16
      historical localities plus one previously unreported site. Most areas inhabited
      by the remaining populations had I(WQ) scores unsuitable for the conservation of
      freshwater biodiversity. Populations showed low but significant genetic
      differentiation with both markers (mtDNA phi(ST) = 0.076, P < 0.001;
      microsatellite F(ST) = 0.314, P < 0.001). Borbollon, in the Cuitzeo Basin, showed
      the highest level of differentiation and was identified as a single genetic unit
      by Bayesian assignment methods. Rio Grande de Morelia and Salamanca populations
      showed the highest genetic diversity and also a high migration rate facilitated
      by an artificial channel that connected the two basins. Overall, high genetic
      diversity values were observed compared with other freshwater fishes (average
      N(a) = 16 alleles and loci and mean +/-S.D. H(o) = 0.63 +/- 0.10 and nucleotide
      diversity pi = 0.006). This suggests that the observed genetic diversity has not
      diminished as rapidly as the species' habitat destruction. No evidence of
      correlation between habitat conditions and genetic diversity was found. The
      current pattern of genetic diversity may be the result of both historical factors
      and recent modifications of the hydrological system. The main threat to the
      species may be the rapid habitat deterioration and associated demographic
      stochasticity rather than genetic factors.

PMID- 23130694
TI  - Developmental structure of the vertebral column, fins, scutes and scales in
      bester sturgeon, a hybrid of beluga Huso huso and sterlet Acipenser ruthenus.
AB  - In the larval bester, a hybrid sturgeon of beluga Huso huso and sterlet Acipenser
      ruthenus, development of cartilage around the notochord began 7 days post hatch
      (dph) (14.0 mm, total length, L(T)). The vertebral cartilage develops in the
      following sequence: basidorsals and basiventrals, neural canals, neural spines
      and ribs. The development of ribs remained incomplete in the largest specimen
      (181 dph, 179 mm L(T) ) that was examined. Endoskeletal development of the fins
      began 4 dph for the dorsal and anal fins, 6 dph for the pectoral fin and 10 dph
      for the caudal and pelvic fins. Complete elements of all fins were observed by 91
      dph and complete ossification of fin rays was observed by 122 dph in the double
      stained specimens. Observation of the histological sections, however, suggested
      that ossification occurred soon after the formation of the organic matrix in the
      fin rays. Dorsal scutes were first visible by 25 dph, followed by the lateral and
      ventral scutes, which were visible by 37 and 44 dph, respectively. The number of
      scutes was fixed at 44, 59 and 91 dph and ossification was complete by 59
      (dorsal) and 91 dph (lateral and ventral scutes) in the double-stained specimens.
      Ossification occurred soon after the formation of the scute organic matrix in the
      histological sections. Four types of scales were observed in the H. huso*A.
      ruthenus hybrid. Median predorsal, preanal and small scales on the anterior
      section of the head were visible by 59 dph. Scales on the caudal fin were visible
      by 91 dph and a variable assemblage of scales anterior to the anal fin was
      visible by 122 dph. Both the scutes and scales developed in a process that is
      similar to that of intramembranous ossification.

PMID- 23130695
TI  - Fish trophic structure in estuaries, with particular emphasis on estuarine
      typology and zoogeography.
AB  - A comparative analysis of the fish trophic structure was undertaken on some 190
      South African estuaries spanning three zoogeographic regions and incorporating
      three broad estuarine types. Fish biomass trophic guild compositions and biomass
      trophic spectrum profiles were analysed using multivariate statistical techniques
      and included both inter-regional (zoogeographic) and intra-regional (estuarine
      typology) comparisons. Differences in the fish trophic structure of the various
      estuary types within each zoogeographic region were observed; these were linked
      to the relative biomass contribution of the various trophic guilds and also to
      differences in biomass trophic spectrum profiles of the fishes in each estuary
      type within each region. In spite of these differences in trophic structure, all
      estuaries were dominated by detritivores, which suggests that the main food
      source (detritus) is similar in all biogeographic regions. Preliminary
      indications are that a similar dependence by estuary-associated fishes on
      detritus food sources exists on a global basis but that detailed studies are
      required in order to confirm this assertion.

PMID- 23130696
TI  - rfishbase: exploring, manipulating and visualizing FishBase data from R.
AB  - This article introduces a package that provides interactive and programmatic
      access to the FishBase repository. This package allows interaction with data on
      over 30 000 fish species in the rich statistical computing environment, R. This
      direct, scriptable interface to FishBase data enables better discovery and
      integration essential for large-scale comparative analyses. This article provides
      several examples to illustrate how the package works, and how it can be
      integrated into phylogenetics packages such as ape and geiger.

PMID- 23130697
TI  - Parasite acquisition by larval coral-reef fishes.
AB  - Of 164 fish larvae belonging to 11 species sampled from the island of Moorea,
      French Polynesia, 30% had at least one parasite individual and parasite
      prevalence ranged between 0 for Chaetodon citrinellus and 80% for Parupeneus
      barberinus. Parasites were present only in larvae that had fed and were present
      in the gut but absent from gills, body cavity and muscle. Parasites appeared to
      be acquired by ingestion of intermediate hosts when the larvae fed on the outer
      slope, prior to reef colonization.

PMID- 23130698
TI  - Isolation of novel microsatellite loci in the black goby Gobius niger and cross
      amplification in other gobiid species (Perciformes, Gobiidae).
AB  - Twelve microsatellite loci were isolated from and characterized for the black
      goby Gobius niger. These loci were tested on a total of 48 individuals from two
      geographically distant locations (Orbetello and Cattolica) and the number of
      alleles ranged from two to 18, with expected (H(e)) and observed (H(o))
      heterozygosities ranging from 0.042 to 0.941 and from 0.042 to 0.917,
      respectively. The loci described were used to cross-amplify other gobiid species
      belonging to Gobius, Zosterisessor, Lesueurigobius and Aphia.

PMID- 23130699
TI  - Manta rays in the Marquesas Islands: first records of Manta birostris in French
      Polynesia and most easterly location of Manta alfredi in the Pacific Ocean, with
      notes on their distribution.
AB  - Based on direct observations of free-ranging specimens, the giant manta ray Manta
      birostris is reported from the Marquesas Islands, the first sighting in French
      Polynesia. Sightings of its sister species, the reef manta ray Manta alfredi, are
      also reported at the most easterly location in the Pacific Ocean. Preliminary
      individual identification as well as notes on their distribution are also
      reported.

PMID- 23130700
TI  - Identification of transferrin in Atlantic cod Gadus morhua epidermal mucus.
AB  - The previously unreported presence of transferrin in Atlantic cod Gadus morhua
      epidermal mucus is described. A less destructive sampling method, which may
      result in decreased epidermal tissue damage, is discussed.

PMID- 23130701
TI  - Tissue preservation biases in stable isotopes of fishes and molluscs from
      Patagonian lakes.
AB  - Field work commonly involves preserving samples for later use; however, most
      preservation methods distort stable-isotope (SI) signatures that are of interest
      to ecologists. Although preservation of muscle samples with table salt and
      rubbing alcohol affected the SI (delta(13)C and delta(15)N) of important
      consumers in Patagonian lakes (molluscs and fishes), variation among individuals
      and lakes generally exceeded that among preservation treatments. Mathematical
      corrections for these preservation biases are provided, and a potentially bias
      free preservation by air-drying is suggested.

PMID- 23130702
TI  - The lunar cycle determines availability of coral-reef fishes at fish markets.
AB  - During 139 visits between March 2009 and May 2011, it was found that the
      availability of reef fishes at a local fish market in the Philippines was highly
      affected by the lunar cycle. The number of vendors selling reef fishes was
      significantly lower (13.4%) during third lunar quarters (full moon periods) than
      during the first, second and fourth lunar quarters (40.2, 25.0 and 30.0%,
      respectively). It is recommended that the influence of the lunar cycle on fish
      availability is considered when designing sampling strategies for catch surveys.

PMID- 23130703
TI  - Extraordinary growth in tiger sharks Galeocerdo cuvier from the South Atlantic
      Ocean.
AB  - Two tagged-and-recaptured tiger sharks Galeocerdo cuvier, measuring 172 and 304
      cm total length (L(T) ) and at age 0.75 and 3.50 years, exhibited unmatched
      growth rates of 118.4 and 55.5 cm year(-1), respectively. The larger fish was
      nearly mature, indicating that G. cuvier off Brazil could mature considerably
      earlier than conspecifics from other regions.

PMID- 23130704
TI  - Empirical standard mass equation for Salmo marmoratus.
AB  - Total length (L(T)) (range 24-1000 mm; mean +/-S.E. = 170.21 +/- 0.36 mm) and
      mass (W) (range 0.10-9590 g; mean +/-S.E. = 76.03 +/- 0.87 g) of 36,460 specimens
      of marble trout Salmo marmoratus were used to compute a standard mass (W(s))
      equation for this species by means of the empirical percentile (EmP) method. The
      EmP W(s) equation calculated was: log(10) W(s) = -5.208 + 3.202 log(10) L(T) -
      0.046 (log(10) L(T))(2) (L(T) range 90-570 mm) and it is valid throughout the
      species' area of distribution across Europe.

PMID- 23130705
TI  - A new record of whale shark Rhincodon typus in Brazilian waters: a report of
      association with Caranx crysos.
AB  - In May 2011, a Rhincodon typus was sighted on the continental shelf of the
      central Brazilian coast, in the vicinity of a gas platform. During the video
      record, an interspecific following association was observed between a Caranx
      crysos school and the R. typus.

PMID- 23130707
TI  - Recent developments in synthesis and structural chemistry of nonaqueous actinide
      complexes.

PMID- 23130706
TI  - Exploring health providers' and community perceptions and experiences with
      malaria tests in South-East Nigeria: a critical step towards appropriate
      treatment.
AB  - BACKGROUND: The adoption of ACT as the first line treatment for uncomplicated
      malaria in Nigeria has concentrated attention on the role of testing in
      appropriate malaria treatment. There are calls at both national and global level
      for malaria treatment to be based on test result, but it is still unclear how
      testing can be incorporated into treatment-seeking and practices of health
      providers. This study explored community members and health providers'
      perceptions and experiences with malaria tests in south east Nigeria. METHODS:
      The study was conducted in urban and rural areas of Enugu state in south-eastern
      Nigeria. A total of 18 focus group discussions with 179 community members
      including sub-groups of primary caregivers, adult men and adult women aged 15
      years and above. Twenty-six (26) In-depth interviews were held with public and
      private health providers involved in prescribing medicines at public and private
      health facilities in the study area. RESULTS: Both providers and community
      members were familiar with malaria tests and identified malaria tests as an
      important step to distinguish malaria from other illnesses with similar symptoms
      and as a means of delivering appropriate treatment. However, the logic of test
      directed treatment was undermined by cost of test and a lack of testing
      facilities but above all concerns over the reliability of negative test results,
      with community members and providers observing inconsistencies between results
      and symptoms, and providers attributing inaccurate results to incompetencies of
      technicians. Recognition of malaria symptoms was deemed most important in
      determining the use of antimalarial drugs rather than the result of a malaria
      test. CONCLUSION: The results highlight important areas of intervention to
      promote appropriate malaria treatment. If tests are to play a role in patient
      management, demand and supply side interventions are needed to change people's
      attitude towards malaria test results.

PMID- 23130708
TI  - Influence of photoperiod in accelerating the reentrainment in Drosophila.
AB  - Efficacy of the short photoperiod (Spp) and the long photoperiod (Lpp) in
      accelerating the reentrainment was assessed in Drosophila biarmipes. The Spp
      accelerated the reentrainment after the phase advance of light-dark (LD) cycles,
      which was associated with the early activity onset (Psio) and the short period of
      free-running rhythm (tau). The Lpp accelerated the reentrainment after the phase
      delay of LD cycles, which was associated with the late Psio and the long tau.
      This study indicates that the photoperiodic modulation of the circadian waveform
      of the underlying pacemaker that controls activity rhythm influenced the rate of
      reentrainment in D. biarmipes.

PMID- 23130709
TI  - Non-neutralizing antibodies in prevention of HIV infection.
AB  - INTRODUCTION: One of the challenges facing the development of an AIDS vaccine is
      eliciting antibody (Ab) capable of preventing the acquisition of HIV. Broadly
      neutralizing Ab (bnAb) that can prevent HIV infection has proven to be difficult
      to elicit. Here, we consider the potential for protective non-neutralizing Ab
      (pnnAb) to provide the much needed Ab component for an HIV vaccine. Such Ab acts
      by "tagging" virus or infected cells for destruction by the innate immune system.
      AREAS COVERED: We review interactions between the Fc region of immunoglobulin G
      (IgG) and FcUpsilon receptors or complement that can lead to the destruction of
      HIV or HIV-infected cells, correlations between the presence of pnnAb and the
      prevention of HIV and simian immunodeficiency virus (SIV) infections, differences
      between classical HIV-specific bnAb and HIV-specific pnnAb, HIV envelope antigens
      and adjuvants which have been hypothesized to generate pnnAb, and the use of
      avidity as a serological correlate for pnnAb. EXPERT OPINION: We hypothesize that
      selection of HIV for the poor ability to elicit bnAb has also selected it for
      slow entry into cells and a window of opportunity for pnnAb to tag virus for
      destruction by innate immune responses.

PMID- 23130712
TI  - CAPs-IDD: Characteristics of Assessment Instruments for Psychiatric Disorders in
      Persons with Intellectual Developmental Disorders.
AB  - BACKGROUND: Assessment of psychiatric disorders in persons with an intellectual
      developmental disorder (IDD) can be performed with a variety of greatly differing
      instruments. This makes the choice of an instrument best suited for the intended
      purpose challenging. In this study, we developed a comprehensive set of
      characteristics for the evaluation and description of assessment instruments for
      psychiatric disorders in adult persons with IDD. This simplifies the search for
      an instrument as it makes an easy and direct comparison possible and hereby
      allows a more thorough and appropriate decision making when selecting assessment
      tools. METHOD: A mixed-methods approach was used. First, a systematic literature
      search was conducted to identify existing tools for the description and
      evaluation of assessment instruments. Second, the content of these tools was
      combined and missing features and IDD-specific attributes were added. Finally,
      expert consultations were performed. RESULTS: The Characteristics of Assessment
      Instruments for Psychiatric Disorders in Persons with Intellectual Developmental
      Disorders (CAPs-IDD) lists characteristics to evaluate and describe instruments
      for psychiatric disorders in persons with IDD. It comprises two sections: first,
      the conceptual and measurement model; second, the psychometric properties. Each
      section consists of various subsections and a detailed response format for coding
      instruments. CONCLUSIONS: The use of the CAPs-IDD helps to identify and choose
      instruments that best suit the respective purpose. Filled with information, it
      could be made accessible via new technologies to researchers and practitioners
      and be updated when new information is available. Thus, it contributes to a more
      reliable and valid assessment of possible psychiatric disorders in persons with
      IDD.

PMID- 23130713
TI  - Approach to the library of 3-hydroxy-1,5-dihydro-2H-pyrrol-2-ones through a three
      component condensation.
AB  - A convenient procedure for the parallel synthesis of 3-hydroxy-1,5-dihydro-2H
      pyrrol-2-ones through a three-component condensation of active methylene
      compounds, aldehydes, and amines was developed. It was shown that the use of
      acetic acid as the reaction medium was suitable for the considerably reactive
      substrates with no additional functionalities. The substrates with low reactivity
      and those possessing carboxylic groups or additional basic centers required the
      use of DMF as the solvent and chlorotrimethylsilane as the reaction promoter was
      necessary. More than 3000 pyrrolones were synthesized by the developed procedure.
      To demonstrate the scope of the described approach 114 library representatives
      were fully characterized.

PMID- 23130721
TI  - Nonlinear analysis of fibrillatory electrogram similarity to optimize the
      detection of complex fractionated electrograms during persistent atrial
      fibrillation.
AB  - INTRODUCTION: Currently, the identification of complex fractionated atrial
      electrograms (CFEs) in the substrate modification is mostly based on cycle length
      derived algorithms. The characteristics of the fibrillation electrogram
      morphology and their consistency over time are not clear. The aim of this study
      was to optimize the detection algorithm of crucial CFEs by using nonlinear
      measure electrogram similarity. METHODS AND RESULTS: One hundred persistent
      atrial fibrillation patients that underwent catheter ablation were included. In
      patients who required CFE ablation (79%), the time-domain fibrillation signals (6
      seconds) were acquired for a linear analysis (mean fractionation interval and
      dominant frequency [DF]) and nonlinear-based waveform similarity analysis of the
      local electrograms, termed the similarity index (SI). Continuous CFEs were
      targeted with an endpoint of termination. Predictors of the various signal
      characteristics on the termination and clinical outcome were investigated.
      Procedural termination was observed in 39% and long-term sinus rhythm maintenance
      in 67% of the patients. The targeted CFEs didn't differ based on the linear
      analysis modalities between the patients who responded and did not respond to CFE
      ablation. In contrast, the average SI of the targeted CFEs was higher in
      termination patients, and they had a better outcome. Multivariate regression
      analysis showed that a higher SI independently predicted sites of termination (>=
      0.57; OR = 4.9; 95% CI = 1.33-18.0; P = 0.017). CONCLUSIONS: In persistent AF
      patients, a cycle length-based linear analysis could not differentiate culprit
      CFEs from bystanders. This study suggested that sites with a high level of
      fibrillation electrogram similarity at the CFE sites were important for AF
      maintenance.

PMID- 23130722
TI  - Innovations, inventions and Dr Archie Brain.

PMID- 23130723
TI  - Where now for thoracic paravertebral blockade?

PMID- 23130724
TI  - The location of paravertebral catheters placed using the landmark technique.
AB  - The aim of this prospective clinical study was to evaluate the location of
      paravertebral catheters that were placed using the classical landmark puncture
      technique and to correlate the distribution of contrast dye injected through the
      catheters with the extent of somatic block. Paravertebral catheter placement was
      attempted in 31 patients after video-assisted thoracic surgery. In one patient,
      an ultrasound-guided approach was chosen after failed catheter placement using
      the landmark method. A fluoroscopic examination in two planes using contrast dye
      was followed by injection of local anaesthetic and subsequent clinical testing of
      the extent of the anaesthetised area. In nine patients (29%), spread of contrast
      dye was not seen within the paravertebral space as intended. Misplaced catheters
      were in the epidural space (three patients), in the erector spinae musculature
      (five patients), and in the pleural space (one patient). There was also a
      discrepancy between the radiological findings and the observed distribution of
      loss of sensation. We have demonstrated an unacceptably high misplacement rate of
      paravertebral catheters using the landmark method. Additional research is
      required to compare the efficacy and safety of continuous paravertebral block
      using ultrasound-guided techniques or surgical inserted catheters.

PMID- 23130725
TI  - Archie Brain: celebrating 30 years of development in laryngeal mask airways.
AB  - The practice of anaesthesia was revolutionised by the ideas of Archie Brain. The
      routine use of a facemask to manage the airway was not a hands-free technique,
      despite the development of various harnesses, and made adequate record-keeping
      difficult. The tracheal tube was associated with some morbidity, which some felt
      was unsuitable for day surgery. Brain developed an airway management device that
      was less stressful to the patient than tracheal intubation, and was, however, as
      safe as using a facemask and airway. Brain also hoped his device would function
      for cases where mask ventilation was particularly difficult and thus give
      anaesthetists a safer alternative to a complex intubation, especially in
      emergency scenarios.

PMID- 23130726
TI  - Christmas decorations as an impediment to patient care.

PMID- 23130727
TI  - Abdominal field block via the lumbar triangle revisited.

PMID- 23130728
TI  - Size matters: choosing the right tracheal tube.

PMID- 23130729
TI  - Size matters: choosing the right tracheal tube.

PMID- 23130731
TI  - Choosing the right tracheal tube: should we use a body length based system?

PMID- 23130732
TI  - Is early withdrawal of treatment after brain injury an inherent conflict of
      interest?

PMID- 23130734
TI  - Broken epidural catheter.

PMID- 23130735
TI  - Alcohol and intensive care.

PMID- 23130736
TI  - Intubating introducers and double-lumen tubes.

PMID- 23130737
TI  - Prevention of regurgitation in patients with subcutaneous oesophageal grafts.

PMID- 23130738
TI  - The effect of the European Working Time Directive on study leave.

PMID- 23130739
TI  - Difficult tracheal intubation in a child with Cornelia de Lange syndrome using a
      paediatric Intlock installed in a Pentax Airway Scope.

PMID- 23130741
TI  - Perioperative outcomes of off-clamp vs complete hilar control laparoscopic
      partial nephrectomy.
AB  - OBJECTIVE: To evaluate perioperative and 6-month renal functional outcomes of
      patients undergoing off-clamp vs complete hilar control laparoscopic partial
      nephrectomy (LPN). PATIENTS AND METHODS: A retrospective review of 489 patients
      undergoing LPN was completed. Preoperative imaging assessed tumour
      characteristics. Patient demographics, perioperative parameters, and
      postoperative outcomes were documented. Multivariable regression analysis was
      used to assess factors contributing to changes in postoperative renal function
      between off-clamp and clamped LPN. RESULTS: In all, 289 LPNs were performed on
      clamp and 150 were performed off-clamp. Tumours in the on-clamp group were larger
      than those in the off-clamp group (mean [range] 3.3 [0.5-13.5] vs 2.7 [0.4-9] cm,
      P = 0.003). Univariable analysis comparing off-clamp to on-clamp cohorts showed
      that estimated glomerular filtration rate (eGFR) was better preserved in the off
      clamp cohort at 6 months (-5.8% vs -11.4%, P = 0.046). Multivariable analysis of
      the groups showed that estimate blood loss (P = 0.015) and warm ischaemia time
      (WIT, P < 0.001) were the only significant predictors of decreased eGFR in the
      postoperative period. Difference in eGFR at 6 months was not significant when WIT
      was limited to 30 min. The complication rate was greater in the clamped cohort
      (10% vs 20%, P = 0.012). There was no difference in transfusion rate or positive
      margin status. CONCLUSIONS: LPN without hilar clamping is feasible, safe and
      associated with less renal injury as assessed by postoperative GFR in select
      patients. With experience, it can be applied to complex renal lesions.

PMID- 23130740
TI  - Treatment outcomes in palliative care: the TOPCare study. A mixed methods phase
      III randomised controlled trial to assess the effectiveness of a nurse-led
      palliative care intervention for HIV positive patients on antiretroviral therapy.
AB  - BACKGROUND: Patients with HIV/AIDS on Antiretroviral Therapy (ART) suffer from
      physical, psychological and spiritual problems. Despite international policy
      explicitly stating that a multidimensional approach such as palliative care
      should be delivered throughout the disease trajectory and alongside treatment,
      the effectiveness of this approach has not been tested in ART-experienced
      populations. METHODS/DESIGN: This mixed methods study uses a Randomised
      Controlled Trial (RCT) to test the null hypothesis that receipt of palliative
      care in addition to standard HIV care does not affect pain compared to standard
      care alone. An additional qualitative component will explore the mechanism of
      action and participant experience. The sample size is designed to detect a
      statistically significant decrease in reported pain, determined by a two tailed
      test and a p value of <=0.05. Recruited patients will be adults on ART for more
      than one month, who report significant pain or symptoms which have lasted for
      more than two weeks (as measured by the African Palliative Care Association
      (APCA) African Palliative Outcome Scale (POS)). The intervention under trial is
      palliative care delivered by an existing HIV facility nurse trained to a set
      standard. Following an initial pilot the study will be delivered in two African
      countries, using two parallel independent Phase III clinical RCTs. Qualitative
      data will be collected from semi structured interviews and documentation from
      clinical encounters, to explore the experience of receiving palliative care in
      this context. DISCUSSION: The data provided by this study will provide evidence
      to inform the improvement of outcomes for people living with HIV and on ART in
      Africa.ClinicalTrials.gov Identifier: NCT01608802.

PMID- 23130742
TI  - Photochemical strategies for the seed-mediated growth of gold and gold-silver
      nanoparticles.
AB  - Gold nanoparticles (AuNP) can be used as seeds for the synthesis of larger AuNP
      of controllable size with narrow size distribution by photochemical reduction of
      additional Au(III) using water-soluble benzoins or H(2)O(2) as sources of
      reducing radicals. Further, beyond simply enlarging the AuNP, it is possible to
      add a shell of another metal, such as silver, leading to Au/Ag core-shell
      structures with controllable dimensions for both core and shell. This strategy
      illustrates the fine spatial and temporal control achievable using clean
      photochemical techniques without the addition of hard surface ligands often
      necessary to control the size and structure of gold-silver nanostructures. The
      mild nature of the surface coverage makes these nanomaterials ideal for further
      surface modification.

PMID- 23130743
TI  - Umbilical cord blood banks. Ethical aspects. Public versus private banks.
AB  - The creation of umbilical cord blood (UCB) banks raises interesting medical,
      social, economic and ethical issues. This paper reviews the ethical problems
      specifically. In this respect, it evaluates: a) whether there are advantages to
      the use of UCB compared to bone marrow, b) whether or not it is ethical to create
      UCB banks, c) whether their creation is ethically acceptable in terms of their
      clinical usefulness or d) the use made of them for therapeutic purposes, and
      finally e) whether their creation is ethically justified from a
      cost/profitability point of view. We focus primarily on evaluating the ethical
      controversy between public and private banks, particularly on whether it is
      ethical to bank autologous blood in private UCB banks, on the basis of its
      limited possibilities for use by the cord blood donor. We can conclude that, from
      an ethical point of view, autologous blood banks have limited acceptance among
      specialised researchers, scientific societies and other public institutions.
      Therefore, we believe that it is ethically more acceptable to support the
      creation of public UCB banks for medical and social reasons and, above all, based
      on the principle of justice and human solidarity. Nevertheless, there is no
      definitive ethical argument why a couple, according to their autonomy and
      freedom, cannot bank their child's UCB in a private bank. An equally acceptable
      solution could be the creation of mixed banks, such as that proposed by the
      Virgin Health Bank or like the Spanish system where autologous samples can be
      stored in public banks but with the proviso that if at any time the stored sample
      is required by any person other than the donor, it would have to be given to
      them.

PMID- 23130744
TI  - [Ethical reflections on cell reprogramming].
AB  - New advances in cell reprogramming, and particularly in obtaining iPS cells, have
      represented a promising possibility for avoiding the use of human embryonic cells
      in experimental research and clinical medicine, use which is ethically
      unacceptable, as obtaining these cells requires the destruction of human embryos.
      The road travelled to arrive at the discovery of iPS cells, and especially the
      ethical assessment of each of the steps taken to that end, are evaluated in this
      paper. The ethical judgement merited by the various uses that can be made of iPS
      cells is also examined, because just when it seemed that iPS cells could resolve
      the ethical problems inherent to the use of embryonic stem cells, new
      possibilities for using iPS cells, especially related with human reproduction,
      have opened up expectations for using these cells that are far removed from the
      most fundamental ethical standards. We conclude that the ethical debate on cell
      reprogramming and particularly on the experimental and clinical use of iPS cells
      remains open.

PMID- 23130745
TI  - [Preimplantatory genetic diagnosis and "saviour sibling": ethical criteria found
      in the biomedical and bioethics literature].
AB  - A bibliographic review on <<saviour sibling>> was performed in order to find out
      the ethical criteria put forward by the authors on this issue. 23 biomedical and
      10 bioethical journals were reviewed and authors for and against the procedure
      were found. In the Biomedical journals, the main arguments for this issue are
      that nobody should be hurt and that there is an ethical imperative that is to
      save a life and that this is preferable to abortion. Those against, believe that
      an inadequate discrimination against women is being exerted on one hand by
      subjecting them to a complex, inefficient and dangerous procedure, and on the
      other, against embryos when many healthy ones are rejected because they are not
      compatible, or because of the dangers to the embryo, and also the psychological
      problems for the sick child as well as the donor. In the bioethical journals, we
      found a higher proportion of papers that are in its favor than in biomedical
      journals. The arguments are similar to those of the bioethical ones, but there
      are some particular arguments such as that the autonomy of parents must be
      respected; that it is a success of the common sense; that it is not an invasive
      process as it is considered; that it only involves blood donation not a solid
      organ; that the child that donates will feel accompanied by the saved one and
      he/she will feel the satisfaction of since having helped someone to live because
      without this procedure, the baby child would probably not have been born. The
      arguments against are the discrimination women undergo when they are subjected to
      this procedure with potential risks for her, the embryos and children. IN
      CONCLUSION: a) the morality of <<saviour sibling>> medicine not has been debated
      in the bioethics and biomedical community before its implementation b) in both
      communities the majority of authors consider it to be ethically licit; c)
      paradoxically there is a greater relative percentage of authors who are critical
      of it within the biomedical field than in bioethics; d) from a personalist
      bioethics perspective a human embryo is endowed with the dignity of a person and
      as such must be respected, this technique being an positive eugenics practice, in
      which, after previous selection health embryos are deprived of their right to
      exist.

PMID- 23130746
TI  - [About <<responsibility>> of vaccination].
AB  - The debate over compulsory or merely recommended vaccination remains open, albeit
      latent, in those countries that have mandatory vaccine schedules. Despite the
      advantages of preventive immunization from the point of medical, economic and
      social features, it's clear, in the current status of medical ethics, that the
      exercise of patient autonomy calls for personal responsibility in the election of
      treatments and, in fact, the vaccines. Therefore, it is necessary to change the
      simple idea of prevention as <<risk reduction>>, characteristic of a <<third
      person ethic>> in order to pass to a preventative medicine concept that will be
      able to support the achievement of moral attitudes towards achieving the good
      <<health>> for the individual and for the community. This is only possible from a
      <<first person ethic>> wherever is possible to present an alternative between
      mandatory vs. recommendation from the concept of <<responsibility>> that, with
      the help of a series of measures, could combine the effective protection for the
      whole community with the responsible exercise of the personal autonomy.

PMID- 23130747
TI  - Nonobstructive hydronephrosis due to social polydipsia: a case report.
AB  - INTRODUCTION: Excessive fluid intake can lead to water intoxication, electrolyte
      abnormalities, exacerbation of heart failure and anatomical changes in the
      urinary tract that may present diagnostic and therapeutic challenges for patients
      and physicians. Although the development of nonobstructive hydronephrosis is
      recognized in patients with central and nephrogenic diabetes insipidus, pregnancy
      or psychiatric polydipsia, it is rarely a diagnostic consideration in healthy
      individuals with excessive fluid ingestion. We now present what we believe to be
      the first report of nonobstructive hydronephrosis associated with social
      polydipsia. CASE PRESENTATION: A 53-year-old African-American woman with moderate
      back pain was found to have bilateral moderate hydronephrosis and hydroureter by
      abdominal computed tomography. She underwent ureteral stent placement followed by
      exploratory laparoscopy with lysis of adhesions and a right oophorectomy, without
      resolution of the nonobstructive hydronephrosis. A careful assessment revealed a
      social habit of consuming approximately 5.5L of fluid daily in an effort to
      remain hydrated in accordance with public health service announcements. It was
      recommended that the patient reduce her fluid intake. A repeat ultrasound after
      six weeks revealed complete resolution of the bilateral hydronephrosis and
      hydroureter. CONCLUSION: Recognition of the nonobstructive nature of
      hydronephrosis caused by polydipsia in healthy individuals is important to
      prevent unnecessary interventions.

PMID- 23130749
TI  - Mapping carrier diffusion in single silicon core-shell nanowires with ultrafast
      optical microscopy.
AB  - Recent success in the fabrication of axial and radial core-shell
      heterostructures, composed of one or more layers with different properties, on
      semiconductor nanowires (NWs) has enabled greater control of NW-based device
      operation for various applications. (1-3)  However, further progress toward
      significant performance enhancements in a given application is hindered by the
      limited knowledge of carrier dynamics in these structures. In particular, the
      strong influence of interfaces between different layers in NWs on transport makes
      it especially important to understand carrier dynamics in these quasi-one
      dimensional systems. Here, we use ultrafast optical microscopy (4)  to directly
      examine carrier relaxation and diffusion in single silicon core-only and
      Si/SiO(2) core-shell NWs with high temporal and spatial resolution in a
      noncontact manner. This enables us to reveal strong coherent phonon oscillations
      and experimentally map electron and hole diffusion currents in individual
      semiconductor NWs for the first time.

PMID- 23130748
TI  - Toward personalized sexual medicine (part 2): testosterone combined with a PDE5
      inhibitor increases sexual satisfaction in women with HSDD and FSAD, and a low
      sensitive system for sexual cues.
AB  - INTRODUCTION: Low sexual desire in women may result from a relative insensitivity
      of the brain for sexual cues. Administration of sublingual 0.5 mg testosterone
      (T) increases the sensitivity of the brain to sexual cues. Sexual stimulation in
      the brain is necessary for phosphodiesterase type 5 inhibitor (PDE5i)-mediated
      increase in genital sexual response. Accordingly, a single dose of T+PDE5i might
      enhance sexual responsiveness, especially in women with low sensitivity for
      sexual cues. AIM: To assess the hypothesis that treatment with on-demand use of
      T+PDE5i improves sexual functioning, particularly in women who suffer from
      Hypoactive Sexual Desire Disorder (HSDD) as the result of a relative
      insensitivity for sexual cues. METHODS: In a randomized, double-blind, placebo
      controlled, crossover design, 56 women with HSDD underwent three medication
      treatment regimes (placebo, T+PDE5i, and T with a serotonin receptor agonist; see
      also parts 1 and 3), which lasted 4 weeks each. In a participant-controlled
      ambulatory psychophysiological experiment at home (the first week of each drug
      treatment), physiological and subjective indices of sexual functioning were
      measured. In a bedroom experiment (the subsequent 3 weeks), sexual functioning
      was evaluated following each sexual event after the self-administration of study
      medication. Subjective evaluation of sexual functioning was also measured by
      weekly and monthly reports. MAIN OUTCOME MEASURES: Subjective: sexual
      satisfaction, experienced genital arousal, sexual desire. Physiological: vaginal
      pulse amplitude. Cognitive: preconscious attentional bias. RESULTS: T+PDE5i, as
      compared with placebo, significantly improved physiological and subjective
      measures of sexual functioning during ambulatory psychophysiological lab
      conditions at home and during the sexual events, in women with low sensitivity
      for sexual cues. CONCLUSIONS: The present study demonstrated that on-demand
      T+PDE5i is a potentially promising treatment for women with HSDD, particularly in
      women with low sensitivity for sexual cues.

PMID- 23130750
TI  - Brief scales to detect postpartum depression and anxiety symptoms.
AB  - BACKGROUND: Depressive and anxiety disorders in the postpartum period cause
      significant suffering for women. State public health officials across the country
      use the Centers for Disease Control and Prevention (CDC)-sponsored Pregnancy Risk
      Assessment Monitoring System (PRAMS) to assess health behaviors and conditions,
      including depression and anxiety, that occur around the time of pregnancy. The
      purpose of the present study was to validate two to three items that could be
      included on the PRAMS questionnaire to detect depression and anxiety among
      postpartum women in a surveillance system. METHODS: A comprehensive set of 16
      depression and anxiety items was developed and tested in a final sample of 1077
      postpartum women, 353 of whom completed Structured Clinical Interview for DSM-IV
      (SCID) interviews to determine the presence of a major depressive episode (MDE)
      and generalized anxiety disorder (GAD). Regression analyses reduced candidate
      items to 5 each for MDE and GAD. Responses were scored on a 5-point scale ranging
      from never (1) to always (5), and 2 and 3 item combinations of these items were
      examined for their psychometric properties as indicators of MDE and GAD. RESULTS:
      Item sets varied in their psychometric properties. The combination of depressed
      mood, felt hopeless, and slowed down >  9 (out of a possible total of 15) yielded
      the highest positive predictive value (PPV=60) and estimated MDE prevalence most
      accurately (24.4% vs. 25.4% true prevalence). The combination of felt panicky,
      felt restless, and problems sleeping >9 estimated GAD prevalence most accurately
      (20.2% vs. 15.7% true prevalence) and had high specificity (83%). CONCLUSIONS:
      Depression and anxiety can be detected using very few items, which makes
      assessment feasible in surveillance systems, such as PRAMS, and in primary care
      settings that have severe limits on time for depression and anxiety screening.

PMID- 23130751
TI  - Development of suspension polymerized molecularly imprinted beads with
      metergoline as template and application in a solid-phase extraction procedure
      toward ergot alkaloids.
AB  - The first successfully developed molecularly imprinted polymer toward six ergot
      alkaloids and their respective epimers is described. A new imprinting molecule,
      metergoline, was used as template analogue in the production of suspension
      polymerized beads. These spherical particles functioned as selective sorbent in a
      solid-phase extraction column. The application of this column in the cleanup of
      barley samples prior to liquid chromatography coupled with tandem mass
      spectrometry allowed simple and cost-efficient sample preparation. The
      performance of the imprinted polymer and a non-imprinted control polymer was
      evaluated. This includes determination of the recovery values and the matrix
      effect of each of the 12 tested ergot alkaloids as well as a cross-reactivity
      study with 25 common mycotoxins. The binding isotherms were obtained for
      metergoline, thus allowing comparison with other (imprinted) sorbents. A
      comparison between bulk and suspension polymerization is provided to determine
      the appropriate production technique.

PMID- 23130753
TI  - MSX1 gene polymorphisms in non-syndromic cleft lip and/or palate.
AB  - OBJECTIVE: The aim of this study was to investigate the contribution of 6
      polymorphic variants of the MSX1 gene in non-syndromic cleft lip and/or palate
      (NSCL/P). METHODS: Three hundred and fifty-eight individuals (158 NSCL/P cases
      and 200 controls) were genotyped by TaqMan allelic discrimination using
      predesigned SNP assays. Statistical analyses were conducted using the software
      spss 15.0 and the r statistical suite. Haplotype block structure and haplotype
      frequencies were determined using the Haploview. A P-value of 0.05 and confidence
      interval of 95% were used for all of statistical tests. RESULTS: The patients
      with non-syndromic cleft lip and/or palate were characterized by similar
      distribution of MSX1 genotypes and allele in comparison to subjects without oral
      clefts (P > 0.05). Two haplotype blocks were constructed with polymorphisms of
      MSX1 gene and haplotypes formed showed a similar frequency in patients with and
      without oral clefts. CONCLUSIONS: The present study provides no evidence that
      MSX1 polymorphisms (rs3775261, rs1042484, rs12532, rs6446693, rs4464513 and
      rs1907998) play a major role in NSCL/P.

PMID- 23130754
TI  - Opportunistic detection of atrial fibrillation in subjects aged 65 years or older
      in primare care: a randomised clinical trial of efficacy. DOFA-AP study protocol.
AB  - BACKGROUND: Clinical Practice Guidelines recommend using peripheral blood pulse
      measuring as a screening test for Atrial Fibrillation. However, there is no
      adequate evidence supporting the efficacy of such procedure in primary care
      clinical practice. This paper describes a study protocol designed to verify
      whether early opportunistic screening for Atrial Fibrillation by measuring blood
      pulse is more effective than regular practice in subjects aged 65 years attending
      primary care centers. METHODS/DESIGN: An cluster-randomized controlled trial
      conducted in Primary Care Centers of the Spanish National Health Service. A total
      of 269 physicians and nurses will be allocated to one of the two arms of the
      trial by stratified randomization with a 3:2 ratio (three practitioners will be
      assigned to the Control Group for every two practitioners assigned to the
      Experimental Group). As many as 12 870 patients aged 65 years or older and
      meeting eligibility criteria will be recruited (8 580 will be allocated to the
      Experimental Group and 4 290 to the Control Group). Randomization and allocation
      to trial groups will be carried out by a central computer system. The
      Experimental Group practitioners will conduct an opportunistic case finding for
      patients with Atrial Fibrillation, while the Control Group practitioners will
      follow the regular guidelines. The first step will be finding new Atrial
      Fibrillation cases. A descriptive inferential analysis will be performed
      (bivariate and multivariate by multilevel logistic regression analysis).
      DISCUSSION: If our hypothesis is confirmed, we expect Primary Care professionals
      to take a more proactive approach and adopt a new protocol when a patient meeting
      the established screening criteria is identified. Finally, we expect this measure
      to be incorporated into Clinical Practice Guidelines. TRIAL REGISTRATION: The
      study is registered as NCT01291953 (ClinicalTrials.gob).

PMID- 23130755
TI  - Progress in the field of necrotising enterocolitis--year 2012.
AB  - Necrotising enterocolitis (NEC) continues to have significant mortality, and
      morbidity including neurodevelopmental impairment, especially in extreme preterm
      neonates needing surgery for the illness. The incidence of NEC has not changed
      significantly despite the advances in neonatal care. Preventing NEC thus remains
      a priority. Protecting the intestinal barrier function and controlling the
      excessive proinflammatory response by the preterm gut are perhaps the most
      important areas for research toward achieving this goal. Improved understanding
      of the role of innate immunity in the pathogenesis of the illness and progress in
      other areas means that novel strategies may become available for the prevention
      and treatment of NEC. Probiotics significantly reduce the risk of NEC. Evidence
      indicates that bovine lactoferrin could reduce both, sepsis and NEC. As new
      frontiers (e.g. oral erythropoietin, heparin binding epithelial growth factor,
      therapeutic hypothermia and stem cell therapy) are being explored, the benefits
      of antenatal glucocorticoids, breast milk and standardised feeding regimes must
      not be forgotten. Preventing sepsis and avoiding undue prolonged exposure to
      antibiotics and antacids will be equally important. Considering the multiple
      complex pathways involved in its pathogenesis, adopting a package of potentially
      better practices will be the most appropriate strategy for prevention and
      treatment of NEC.

PMID- 23130756
TI  - Comparing costs of robotic, laparoscopic, and open partial nephrectomy.
AB  - Abstract Background and Purpose: Laparoscopic and robot-assisted partial
      nephrectomy (LPN and RPN) are common minimally invasive alternatives to open
      partial nephrectomy (OPN) for management of renal tumors. Cost discrepancies of
      these approaches warrants evaluation. We compared hospital costs associated with
      RPN, LPN, and OPN. PATIENTS AND METHODS: Costs were captured for 25 patients in
      each group who underwent RPN, LPN, or OPN at our institution between November
      2008 and September 2010. Variable costs included operating room (OR) time,
      supplies, anesthesia, and inpatient care costs. Fixed costs included equipment
      purchase and maintenance. Impact of variable and fixed costs were estimated using
      sensitivity analysis. RESULTS: Overall variable costs were similar for RPN, LPN,
      and OPN ($6375 vs $6075 vs $5774, P=0.117, respectively). OR supplies contributed
      a greater cost for RPN and LPN than OPN ($2179 vs $1987 vs $181, P<0.0001,
      respectively), while inpatient stay costs were higher for OPN compared with LPN
      and RPN ($2418 vs $1305 vs $1274, P<0.0001, respectively). Sensitivity analysis
      of variable costs demonstrates that RPN and LPN can represent less costly
      alternatives to OPN if hospital stay for RPN and LPN is <=2 days and OR time <195
      and 224 minutes, respectively. Inclusion of fixed costs made OPN less expensive
      than LPN and RPN unless use of the robot increases and operative times are
      reduced. CONCLUSION: By minimizing OR time and hospital stay, RPN and LPN can be
      cost equivalent to OPN regarding variable costs. When including fixed costs, RPN
      and LPN were more costly than OPN, but equivalence may be possible with
      improvements in efficiency.

PMID- 23130757
TI  - Circadian typology and sensation seeking in adolescents.
AB  - The relationship of circadian typology with personality has been largely studied
      in adults, but there are few studies exploring such relationship in adolescents.
      Adolescence has been associated with a greater tendency to eveningness
      preference, sleeping problems, poorer academic achievement, earlier substance
      use, or risky behaviors, and it is suggested that this association might be
      mediated by personality factors. Given the relevance of identifying the
      behavioral outcomes of young evening types to detect and prevent health problems,
      the present study aimed to explore, for the first time, the relationship between
      sensation seeking and circadian typology in an adolescent sample of 688 students
      (51.45% boys) from 12 to 16 yrs old. They answered the Spanish versions of the
      Morningness-Eveningness Scale for Children (MESC) and the Junior Sensation
      Seeking Scale (J-SSS), which includes four subscales measuring Thrill and
      Adventure Seeking, Experience Seeking, Disinhibition, and Boredom Susceptibility.
      Analyses showed that boys obtained significantly higher scores than girls on J
      SSS total score and all subscales except Boredom Susceptibility, whereas evening
      type adolescents of both sexes scored significantly higher than neither types and
      than morning types on J-SSS total score. These results indicate that evening-type
      adolescents show a greater desire for varied, new, complex, and intense
      sensations, and they are ready for experiencing more risks than morning types.
      The implications of this study suggest the need of being aware of individual
      differences in the SS trait in evening-type adolescents, as well as taking into
      account the wide variety of behaviors associated with it, either prosocial or
      antisocial, to design better preventive health and academic programs.

PMID- 23130758
TI  - High proton conductivity by a metal-organic framework incorporating Zn8O clusters
      with aligned imidazolium groups decorating the channels.
AB  - A novel metal-organic framework,
      [{(Zn(0.25))(8)(O)}Zn(6)(L)(12)(H(2)O)(29)(DMF)(69)(NO(3))(2)](n) (1) {H(2)L =
      1,3-bis(4-carboxyphenyl)imidazolium}, has been synthesized under solvothermal
      conditions in good yield. It shows a Zn(8)O cluster that is coordinated to six
      ligands and forms an overall three-dimensional structure with channels along the
      crystallographic a and b axes. The imidazolium groups of the ligand moiety are
      aligned in the channels. The channels are not empty but are occupied by a large
      number of DMF and water molecules. Upon heating, these solvent molecules can be
      removed without breakdown of the overall structure of the framework as shown by
      variable-temperature powder X-ray diffraction patterns. Of great interest is the
      fact that the compound exhibits high proton conductivity with a low activation
      energy that is comparable to those of Nafion presently used in fuel cells.

PMID- 23130759
TI  - Forensic applications of light-element stable isotope ratios of Ricinus communis
      seeds and ricin preparations.
AB  - Seeds of the castor plant Ricinus communis are of forensic interest because they
      are the source of the poison ricin. We tested whether stable isotope ratios of
      castor seeds and ricin preparations can be used as a forensic signature. We
      collected over 300 castor seed samples worldwide and measured the C, N, O, and H
      isotope ratios of the whole seeds and oil. We prepared ricin by three different
      procedures, acetone extraction, salt precipitation, and affinity chromatography,
      and compared their isotope ratios to those of the source seeds. The N isotope
      ratios of the ricin samples and source seeds were virtually identical. Therefore,
      N isotope ratios can be used to correlate ricin prepared by any of these methods
      to source seeds. Further, stable isotope ratios distinguished >99% of crude and
      purified ricin protein samples in pairwise comparison tests. Stable isotope
      ratios therefore constitute a valuable forensic signature for ricin preparations.

PMID- 23130760
TI  - No association between the STAT5b rs6503691 (C>T) SNP and myeloproliferative
      neoplasms.

PMID- 23130761
TI  - Vaginal microbicides for reducing the risk of sexual acquisition of HIV infection
      in women: systematic review and meta-analysis.
AB  - BACKGROUND: Each year more than two million people are newly infected with HIV
      worldwide, a majority of them through unprotected vaginal sex. More than half of
      new infections in adults occur in women. Male condoms and male circumcision
      reduce the risk of HIV acquisition; but the uptake of these methods is out of the
      control of women. We therefore aimed to determine the effectiveness of vaginal
      microbicides (a potential female-controlled method) for prevention of sexual
      acquisition of HIV in women. METHODS: We conducted a comprehensive search of peer
      reviewed and grey literature for publications of randomised controlled trials
      available by September 2012. We screened search outputs, selected studies,
      assessed risk of bias, and extracted data in duplicate; resolving differences by
      discussion and consensus. RESULTS: We identified 13 eligible trials that compared
      vaginal microbicides to placebo. These studies enrolled 35,905 sexually active
      HIV-negative women between 1996 and 2011; in Benin, Cameroon, Cote d'Ivoire,
      Ghana, Kenya, Malawi, Nigeria, South Africa, Tanzania, Uganda, Zambia, Zimbabwe,
      India, Thailand, and the United States of America. A small trial of 889 women
      found that tenofovir (a nucleotide reverse transcriptase inhibitor) significantly
      reduces the risk of HIV acquisition (risk ratio [RR] 0.63, 95% confidence
      intervals [CI] 0.43 to 0.93). Effectiveness data are not yet available from
      follow-up tenofovir trials being conducted in South Africa, Uganda, and Zimbabwe
      (1 trial) and multiple sites in South Africa (1 trial). We found no evidence of a
      significant effect for nonoxynol-9 (5 trials), cellulose sulphate (2 trials),
      SAVVY (2 trials), Carraguard (1 trial), PRO 2000 (2 trials), and BufferGel (1
      trial) microbicides. The pooled RR for the effect of current experimental vaginal
      microbicides on HIV acquisition in women was 0.97, 95%CI 0.87 to 1.08. Although
      study results were homogeneous across the different drug classes (heterogeneity P
      = 0.17, I2 = 27%), the overall intervention effect was not statistically
      significant. Nonoxynol-9 significantly increased the risk of having adverse
      genital lesions but no other microbicide led to significant increases in adverse
      events. CONCLUSIONS: There is not enough evidence at present to recommend vaginal
      microbicides for HIV prevention. Further high-quality research is needed to
      confirm the beneficial effects of tenofovir as well as continue the development
      and testing of new microbicides.

PMID- 23130762
TI  - Local government alcohol policy development: case studies in three New Zealand
      communities.
AB  - AIMS: Local alcohol policies can be effective in reducing alcohol-related harm.
      The aim of this study was to examine local government responses to alcohol
      related problems and identify factors influencing their development and adoption
      of alcohol policy. DESIGNSETTINGS AND PARTICIPANTS: Case studies were used to
      examine local government responses to alcohol problems in three New Zealand
      communities: a rural town, a provincial city and a metropolitan city. Newspaper
      reports, local government documents and key informant interviews were used to
      collect data which were analysed using two conceptual frameworks: Kingdon's
      Streams model and the Stakeholder model of policy development. MEASUREMENTS: Key
      informant narratives were categorized according to the concepts of the Streams
      and Stakeholder models. FINDINGS: Kingdon's theoretical concepts associated with
      increased likelihood of policy change seemed to apply in the rural and
      metropolitan communities. The political environment in the provincial city,
      however, was not favourable to the adoption of alcohol restrictions. The
      Stakeholder model highlighted differences between the communities in terms of
      power over agenda-setting and conflict between politicians and bureaucrats over
      policy solutions to alcohol-related harm. These differences were reflected in the
      ratio of policies considered versus adopted in each location. Decisions on local
      alcohol policies lie ultimately with local politicians, although the policies
      that can be adopted by local government are restricted by central government
      legislation. CONCLUSIONS: The adoption of policies and strategies to reduce
      alcohol-related harm may be better facilitated by an agenda-setting process where
      no 'gate-keepers' determine what is included into the agenda, and community
      mobilization efforts to create competitive local government elections around
      alcohol issues. Policy adoption would also be facilitated by more enabling
      central government legislation.

PMID- 23130763
TI  - Perioperative outcomes of off-clamp vs complete hilar control laparoscopic
      partial nephrectomy.

PMID- 23130764
TI  - Commentary: PPIs and risk of serious infection in decompensated cirrhosis.

PMID- 23130766
TI  - Commentary: Predicting response to ciclosporin in acute severe ulcerative
      colitis.

PMID- 23130768
TI  - Commentary: Physical activity and NAFLD--cause or effect?

PMID- 23130770
TI  - Commentary: Psychological disorders linked to functional dyspepsia.

PMID- 23130772
TI  - Commentary: The link between community-acquired pneumonia and PPI use.

PMID- 23130773
TI  - Letter: Surveillance of Helicobacter pylori antibiotic resistance.

PMID- 23130775
TI  - Letter: Vaptans for the treatment of hyponatraemia and ascites in patients with
      cirrhosis.

PMID- 23130778
TI  - Letter: Potential chemopreventive effects of statins in oesophageal
      adenocarcinoma.

PMID- 23130779
TI  - Letter: The effects of preoperative infliximab on complications after surgery for
      ulcerative colitis.

PMID- 23130781
TI  - Clinical characteristics, mortality, cardiac hospitalization, and ventricular
      arrhythmias in patients undergoing CRT-D implantation: results of the ACTION-HF
      study.
AB  - INTRODUCTION: The characteristics and outcomes of patients who undergo cardiac
      resynchronization therapy (CRT) device implantation in current clinical practice
      may differ from those of reference trial populations. Study objectives were to
      assess 2-year outcomes in a population implanted with a CRT plus defibrillator
      device in accordance with the standard of care and to evaluate any independent
      association between clinical variables and outcome. METHODS AND RESULTS: A total
      of 406 patients enrolled at 35 centers in Italy were followed up prospectively
      for 2 years. All patient management decisions were left to the treating
      physician's discretion, in accordance with clinical practice. ACTION-HF patients
      had a better baseline clinical status than patients enrolled in the COMPANION
      study: shorter HF history (1 vs 3.5 years, P < 0.01), less advanced NYHA
      functional class (III-IV: 73% vs 100%, P < 0.01), higher LVEF (26% vs 21%, P <
      0.01), higher SBP (122 vs 112 mmHg, P < 0.01), and less diabetes (27% vs 41%, P <
      0.01). This status was reflected in lower mortality (11.5% vs 26%) and a lower
      incidence of appropriate ICD shocks (12.1% vs 19.3%). AF history was an
      independent predictor of the combination of all-cause mortality and cardiac-cause
      hospitalization (HR: 3.31; P < 0.001). Recurrent or new atrial arrhythmias were
      independently associated with the development of ventricular arrhythmias (HR:
      3.4; P < 0.001). CONCLUSIONS: This population appears clinically less compromised
      and had a lower incidence of adverse clinical outcomes than those of reference
      trials. However, we recorded a substantial burden of atrial arrhythmias, which
      was independently associated with a higher incidence of ventricular arrhythmias.

PMID- 23130782
TI  - Toward personalized sexual medicine (part 1): integrating the "dual control
      model" into differential drug treatments for hypoactive sexual desire disorder
      and female sexual arousal disorder.
AB  - In three related manuscripts we describe our drug development program for the
      treatment of Hypoactive Sexual Desire Disorder (HSDD). In this first theoretical
      article we will defend the hypothesis that different causal mechanisms are
      responsible for the emergence of HSDD: low sexual desire in women (with HSDD)
      could be due to either a relative insensitive brain system for sexual cues or to
      enhanced activity of sexual inhibitory mechanisms. This distinction in
      etiological background was taken into account when designing and developing new
      pharmacotherapies for this disorder. Irrespective of circulating plasma levels of
      testosterone, administration of sublingual 0.5 mg testosterone increases the
      sensitivity of the brain to sexual cues. The effects of an increase in sexual
      sensitivity of the brain depend on the motivational state of an individual. It
      might activate sexual excitatory mechanisms in low sensitive women, while it
      could evoke (or strengthen) sexual inhibitory mechanisms in women prone to sexual
      inhibition. Sexual stimulation in the brain is necessary for phosphodiesterase
      type 5 inhibitor (PDE5i)-mediated increase in genital sexual response.
      Accordingly, a single dose of T+PDE5i might enhance sexual responsiveness,
      especially in women with low sensitivity to sexual cues. In other women sexual
      stimulation might elicit a prefrontal cortex (PFC)-mediated phasic increase in
      sexual inhibition, in which activity of 5-hydroxytryptamine (5-HT, serotonin) is
      involved. We hypothesize that a single dose of 5-hydroxytryptamine receptor
      agonist (5-HT(1A)ra) will reduce the sexual-stimulation-induced PFC-mediated
      sexual inhibition during a short period after administration. Consequently,
      treatment with T+5-HT(1A)ra will be more effective, in particular in women
      exhibiting sexual inhibition. Based on the results of our efficacy studies
      described in parts 2 and 3 of the series, we conclude that tailoring on-demand
      therapeutics to different underlying etiologies might be a useful approach to
      treat common symptoms in subgroups of women with HSDD.

PMID- 23130784
TI  - Synthesis of 2-phenyl-4,5-substituted oxazoles by copper-catalyzed intramolecular
      cyclization of functionalized enamides.
AB  - An efficient two-step synthesis of 2-phenyl-4,5-substituted oxazoles involving
      intramolecular copper-catalyzed cyclization of highly functionalized novel beta
      (methylthio)enamides as the key step has been reported. These enamides are
      obtained by nucleophilic ring-opening of newly synthesized 4
      [(methylthio)hetero(aryl)methylene]-2-phenyl-5-oxazolone precursors by alkoxides,
      amines, amino acid esters and aryl/alkyl Grignard reagents, thus leading to the
      introduction of an ester, N-substituted carboxamide or acyl functionalities at 4
      position of the product oxazoles. Synthesis of two naturally occurring 2,5
      diaryloxazoles, i.e., texamine and uguenenazole, via two-step hydrolysis
      decarboxylation of the corresponding 2,5-diaryloxazole-4-carboxylates has also
      been described. Similarly, three of the serine-derived oxazole-4-carboxamides
      were elaborated to novel trisubstituted 4,2'-bisoxazoles through DAST/DBU
      mediated cyclodehydration-dehydrohalogenation sequence. The present protocol is
      complementary and an improvement to our previously reported silver carbonate
      induced cyclization of beta-bis(methylthio)enamides to 2-phenyl-5-(methylthio)-4
      substituted oxazoles.

PMID- 23130783
TI  - Oxygen: friend or foe in peri-operative care?

PMID- 23130785
TI  - Spontaneous nucleation and growth of GaN nanowires: the fundamental role of
      crystal polarity.
AB  - We experimentally investigate whether crystal polarity affects the growth of GaN
      nanowires in plasma-assisted molecular beam epitaxy and whether their formation
      has to be induced by defects. For this purpose, we prepare smooth and coherently
      strained AlN layers on 6H-SiC(0001) and SiC(0001) substrates to ensure a well
      defined polarity and an absence of structural and morphological defects. On N
      polar AlN, a homogeneous and dense N-polar GaN nanowire array forms, evidencing
      that GaN nanowires form spontaneously in the absence of defects. On Al-polar AlN,
      we do not observe the formation of Ga-polar GaN NWs. Instead, sparse N-polar GaN
      nanowires grow embedded in a Ga-polar GaN layer. These N-polar GaN nanowires are
      shown to be accidental in that the necessary polarity inversion is induced by the
      formation of Si(x)N. The present findings thus demonstrate that spontaneously
      formed GaN nanowires are irrevocably N-polar. Due to the strong impact of the
      polarity on the properties of GaN-based devices, these results are not only
      essential to understand the spontaneous formation of GaN nanowires but also of
      high technological relevance.

PMID- 23130786
TI  - Quantifying high-affinity binding of hydrophobic ligands by isothermal titration
      calorimetry.
AB  - A fast and reliable quantification of the binding thermodynamics of hydrophobic
      high-affinity ligands employing a new calorimetric competition experiment is
      described. Although isothermal titration calorimetry is the method of choice for
      a quantitative characterization of intermolecular interactions in solution, a
      reliable determination of a dissociation constant (K(D)) is typically limited to
      the range 100 MUM > K(D) > 1 nM. Interactions displaying higher or lower K(D)
      values can be assessed indirectly, provided that a suitable competing ligand is
      available whose K(D) falls within the directly accessible affinity window. This
      established displacement assay, however, requires the high-affinity ligand to be
      soluble at high concentrations in aqueous buffer and, consequently, poses serious
      problems in the study of protein binding involving small-molecule ligands
      dissolved in organic solvents--a familiar case in many drug-discovery projects
      relying on compound libraries. The calorimetric competition assay introduced here
      overcomes this limitation, thus allowing for a detailed thermodynamic description
      of high-affinity receptor-ligand interactions involving poorly water-soluble
      compounds. Based on a single titration of receptor into a dilute mixture of the
      two competing ligands, this competition assay provides accurate and precise
      values for the dissociation constants and binding enthalpies of both high- and
      moderate-affinity ligands. We discuss the theoretical background underlying the
      approach, demonstrate its practical application to metal ion chelation and high
      affinity protein-inhibitor interactions, and explore its potential and
      limitations with the aid of simulations and statistical analyses.

PMID- 23130787
TI  - High-resolution charge exchange measurements at ASDEX Upgrade.
AB  - The charge exchange recombination spectroscopy (CXRS) diagnostics at ASDEX
      Upgrade (AUG) have been upgraded and extended to provide high-resolution
      measurements of impurity ion temperature, density, and rotation profiles. The
      existing core toroidal CXRS diagnostic has been refurbished to increase the level
      of signal, thus enabling shorter exposure times down to 3.5 ms. Additional lines
      of sight provide more detailed profiles and enable simultaneous measurements of
      multiple impurities. In addition, a new CXRS system has been installed, which
      allows for the measurement of poloidal impurity ion rotation in the plasma edge
      with high temporal (1.9 ms) and spatial resolution (down to 5 mm). A new
      wavelength correction method has been implemented to perform in situ wavelength
      calibrations on a shot-to-shot basis. Absolute measurements of the poloidal
      impurity ion rotation with uncertainties smaller than 1.5 km/s have been
      obtained. Comparison of all the CXRS measurements provides a consistency check of
      the diagnostics and good agreement has been found for all of the CXRS systems.

PMID- 23130788
TI  - Exploration of ion temperature profile measurements at JET using the upgraded
      neutron profile monitor.
AB  - The neutron profile monitor (NPM), routinely used at the Joint European Torus for
      neutron emissivity profile measurements, consists of two fan-shaped arrays of
      collimators and each line of sight (LOS) is equipped with a NE213 liquid organic
      scintillator for simultaneous measurements of the 2.5 MeV and 14 MeV neutrons. A
      digital system developed in ENEA has replaced the analog acquisition electronics
      and now enables the NPM to perform spatially resolved neutron spectrometry by
      providing neutron pulse height spectra (PHS) for each LOS. However, the NPM was
      not originally designed as a spectrometer and, therefore, lacks several key
      features, such as detailed measurements of the detector response functions and
      the presence of detector stability monitors. We present a proof of principle of
      ion temperature profile measurements derived from the NPM PHS in high plasma
      current discharges using simulated detector response functions.

PMID- 23130789
TI  - Implementation of an in-vessel calibration light source for JET.
AB  - An in-vessel calibration light source (ICLS) has been implemented for remote use
      during extended shutdown periods of the Joint European Torus (JET). The ICLS
      facilitated the in situ calibration of optical diagnostics, which previously were
      performed when the diagnostics were removed from JET. Since the ICLS is used to
      calibrate diagnostics over the entire, exact optical path as used when plasma
      discharge data are measured, the ICLS calibration implicitly accounts for any
      vignetting losses in the JET vessel viewports in addition to the vacuum window
      transmission. At least ten diagnostic systems have benefited from the ICLS during
      the extended ITER-like wall shutdown of 2009-2011. Examples of the use of the
      ICLS in JET are given.

PMID- 23130790
TI  - Development of a mirror-based endoscope for divertor spectroscopy on JET with the
      new ITER-like wall (invited).
AB  - A new endoscope with optimised divertor view has been developed in order to
      survey and monitor the emission of specific impurities such as tungsten and the
      remaining carbon as well as beryllium in the tungsten divertor of JET after the
      implementation of the ITER-like wall in 2011. The endoscope is a prototype for
      testing an ITER relevant design concept based on reflective optics only. It may
      be subject to high neutron fluxes as expected in ITER. The operating wavelength
      range, from 390 nm to 2500 nm, allows the measurements of the emission of all
      expected impurities (W I, Be II, C I, C II, C III) with high optical
      transmittance (>= 30% in the designed wavelength range) as well as high spatial
      resolution that is <= 2 mm at the object plane and <= 3 mm for the full depth of
      field (+/- 0.7 m). The new optical design includes options for in situ
      calibration of the endoscope transmittance during the experimental campaign,
      which allows the continuous tracing of possible transmittance degradation with
      time due to impurity deposition and erosion by fast neutral particles. In
      parallel to the new optical design, a new type of possibly ITER relevant shutter
      system based on pneumatic techniques has been developed and integrated into the
      endoscope head. The endoscope is equipped with four digital CCD cameras, each
      combined with two filter wheels for narrow band interference and neutral density
      filters. Additionally, two protection cameras in the lambda > 0.95 MUm range have
      been integrated in the optical design for the real time wall protection during
      the plasma operation of JET.

PMID- 23130791
TI  - A new visible spectroscopy diagnostic for the JET ITER-like wall main chamber.
AB  - In preparation for ITER, JET has been upgraded with a new ITER-like wall (ILW),
      whereby the main plasma facing components, previously of carbon, have been
      replaced by mainly Be in the main chamber and W in the divertor. As part of the
      many diagnostic enhancements, a new, survey, visible spectroscopy diagnostic has
      been installed for the characterization of the ILW. An array of eight lines-of
      sight (LOS) view radially one of the two JET neutral beam shine through areas (W
      coated carbon fibre composite tiles) at the inner wall. In addition, one vertical
      LOS views the solid W tile at the outer divertor. The light emitted from the
      plasma is coupled to a series of compact overview spectrometers, with overall
      wavelength range of 380-960 nm and to one high resolution Echelle overview
      spectrometer covering the wavelength range 365-720 nm. The new survey diagnostic
      has been absolutely calibrated in situ by means of a radiometric light source
      placed inside the JET vessel in front of the whole optical path and operated by
      remote handling. The diagnostic is operated in every JET discharge, routinely
      monitoring photon fluxes from intrinsic and extrinsic impurities (e.g., Be, C, W,
      N, and Ne), molecules (e.g., BeD, D(2), ND) and main chamber and divertor
      recycling (typically Dalpha, Dbeta, and Dgamma). The paper presents a technical
      description of the diagnostic and first measurements during JET discharges.

PMID- 23130792
TI  - Modeling of the ITER-like wide-angle infrared thermography view of JET.
AB  - Infrared (IR) thermography systems are mandatory to ensure safe plasma operation
      in fusion devices. However, IR measurements are made much more complicated in
      metallic environment because of the spurious contributions of the reflected
      fluxes. This paper presents a full predictive photonic simulation able to assess
      accurately the surface temperature measurement with classical IR thermography
      from a given plasma scenario and by taking into account the optical properties of
      PFCs materials. This simulation has been carried out the ITER-like wide angle
      infrared camera view of JET in comparing with experimental data. The consequences
      and the effects of the low emissivity and the bidirectional reflectivity
      distribution function used in the model for the metallic PFCs on the contribution
      of the reflected flux in the analysis are discussed.

PMID- 23130793
TI  - Upgrade of the infrared camera diagnostics for the JET ITER-like wall divertor.
AB  - For the new ITER-like wall at JET, two new infrared diagnostics (KL9B, KL3B) have
      been installed. These diagnostics can operate between 3.5 and 5 MUm and up to
      sampling frequencies of ~20 kHz. KL9B and KL3B image the horizontal and vertical
      tiles of the divertor. The divertor tiles are tungsten coated carbon fiber
      composite except the central tile which is bulk tungsten and consists of lamella
      segments. The thermal emission between lamellae affects the surface temperature
      measurement and therefore KL9A has been upgraded to achieve a higher spatial
      resolution (by a factor of 2). A technical description of KL9A, KL9B, and KL3B
      and cross correlation with a near infrared camera and a two-color pyrometer is
      presented.

PMID- 23130794
TI  - Recent improvements of the JET lithium beam diagnostic.
AB  - A 60 kV neutral lithium diagnostic beam probes the edge plasma of JET for the
      measurement of electron density profiles. This paper describes recent
      enhancements of the diagnostic setup, new procedures for calibration and
      protection measures for the lithium ion gun during massive gas puffs for
      disruption mitigation. New light splitting optics allow in parallel beam emission
      measurements with a new double entrance slit CCD spectrometer (spectrally
      resolved) and a new interference filter avalanche photodiode camera (fast density
      and fluctuation studies).

PMID- 23130795
TI  - Enhancements to the JET poloidally scanning vacuum ultraviolet/visible
      spectrometers.
AB  - Enhancements to the JET poloidally scanning spectrometers are presented, which
      will aid the exploitation of the recently installed ITER-like wall in JET. They
      include the installation of visible filter/photomultiplier tube assemblies and
      spectrometers and the replacement of large rotating mirrors in the JET vacuum
      with small oscillating mirrors outside. The upgrade has resulted in a more robust
      and reliable diagnostic than before, which is described. Drifts in the mirror
      angle reconstructed from quadrature encoder signals are found, a reference signal
      being required. The use of the small scanning mirrors necessitated the inclusion
      of focusing mirrors to maintain throughput into the vacuum ultraviolet
      spectrometers. The mirror design has taken account of the extreme sensitivity of
      the focusing to the grazing angle of incidence, an aspect of importance in the
      design of grazing incidence focusing components on future machines, such as ITER.
      The visible system has been absolutely calibrated using an in-vessel light
      source.

PMID- 23130796
TI  - A protection system for the JET ITER-like wall based on imaging diagnostics.
AB  - The new JET ITER-like wall (made of beryllium and tungsten) is more fragile than
      the former carbon fiber composite wall and requires active protection to prevent
      excessive heat loads on the plasma facing components (PFC). Analog CCD cameras
      operating in the near infrared wavelength are used to measure surface temperature
      of the PFCs. Region of interest (ROI) analysis is performed in real time and the
      maximum temperature measured in each ROI is sent to the vessel thermal map. The
      protection of the ITER-like wall system started in October 2011 and has already
      successfully led to a safe landing of the plasma when hot spots were observed on
      the Be main chamber PFCs. Divertor protection is more of a challenge due to dust
      deposits that often generate false hot spots. In this contribution we describe
      the camera, data capture and real time processing systems. We discuss the
      calibration strategy for the temperature measurements with cross validation with
      thermal IR cameras and bi-color pyrometers. Most importantly, we demonstrate that
      a protection system based on CCD cameras can work and show examples of hot spot
      detections that stop the plasma pulse. The limits of such a design and the
      associated constraints on the operations are also presented.

PMID- 23130797
TI  - JET divertor diagnostic upgrade for neutral gas analysis.
AB  - With installation of the ITER-like wall in JET a major diagnostic upgrade to
      measure the neutral gas pressure and composition in the sub-divertor region has
      been completed, to characterise retention and outgassing of the new metallic
      first wall. The upgrade includes two new magnetically shielded systems consisting
      of sensitive capacitance manometers and residual gas analysers, both capable of
      providing data during plasma operation. These enable absolute pressure and gas
      composition measurements (pressure range: 10(-5)-10(-1) mbar, mass range: 1-200
      amu, respectively) and have been used to characterise the neutral gas behaviour
      under various plasma conditions.

PMID- 23130798
TI  - Fully digital data acquisition system for the neutron time-of-flight spectrometer
      TOFOR at JET.
AB  - A prototype of a fully digital data acquisition system based on 1 Gsps 12 bit
      digitizers for the TOFOR fusion neutron spectrometer at JET is assessed. The
      prototype system enables the use of geometry-based background discrimination
      techniques, which are modeled, evaluated, and compared to experimental data. The
      experimental results are in line with the models and show a significant
      improvement in signal-to-background ratio in measured time-of-flight spectrum
      compared to the existing data acquisition system.

PMID- 23130799
TI  - Fuel ion ratio measurements in reactor relevant neutral beam heated fusion
      plasmas.
AB  - In this paper, we present a method to derive n(t)/n(d) using the ratio of the
      thermonuclear neutron emission to the beam-target neutron emission. We apply it
      to neutron spectroscopy data from the magnetic proton recoil spectrometer taken
      during the deuterium tritium experiment at JET. n(t)/n(d)-values obtained using
      neutron spectroscopy are in qualitative agreement with those from other
      diagnostics measuring the isotopic composition of the exhaust in the divertor.

PMID- 23130800
TI  - Neutron field parameter measurements on the JET tokamak by means of super-heated
      fluid detectors.
AB  - The neutron field parameters (fluence and energy distribution) at a specific
      location outside the JET Torus Hall have been measured by means of super-heated
      fluid detectors (or "bubble detectors") in combination with an independent, time
      of-flight, technique. The bubble detector assemblies were placed at the end of a
      vertical line of sight at about 16 m from the tokamak mid plane. Spatial
      distributions of the neutron fluence along the radial and toroidal directions
      have been obtained using two-dimensional arrays of bubble detectors. Using a set
      of three bubble detector spectrometers the neutron energy distribution was
      determined over a broad energy range, from about 10 keV to above 10 MeV, with an
      energy resolution of about 30% at 2.5 MeV. The very broad energy response allowed
      for the identification of energy features far from the main fusion component
      (around 2.45 MeV for deuterium discharges).

PMID- 23130801
TI  - Density profile measurements with X-mode lower cut-off reflectometry in ASDEX
      Upgrade.
AB  - Despite the fact that density profile measurements using X-mode lower cut-off
      reflectometry are foreseen to be used on ITER, little or no experience is
      available within the reflectometry community and to our knowledge no results on
      this subject have been published so far. In ASDEX Upgrade the multichannel
      broadband reflectometer is equipped with both O- and X-mode channels. While X
      mode operation was designed for upper cut-off reflection, it is observed that for
      both high magnetic field and high density discharges the lower cut-off becomes
      accessible. Here we present reflectometry measurements obtained in ASDEX Upgrade
      using X-mode lower cut-off and compare both the resulting group delay and density
      profile with O-mode measurements performed simultaneously over the same plasma
      region. The possible use of this comparison to provide estimates of the magnetic
      field is briefly discussed.

PMID- 23130802
TI  - Novel mono-static arrangement of the ASDEX Upgrade high field side reflectometers
      compatible with electron cyclotron resonance heating stray radiation.
AB  - The ASDEX Upgrade frequency modulated continuous wave broadband reflectometer
      system uses a mono-static antenna configuration with in-vessel hog-horns and 3 dB
      directional couplers. The operation of the new electron cyclotron resonance
      heating (ECRH) launcher and the start of collective Thomson scattering
      experiments caused several events where the fragile dummy loads inside the high
      field side directional couplers were damaged, due to excessive power resulting
      from the ECRH stray fields. In this paper, we present a non-conventional
      application of the existing three-port directional coupler that hardens the
      system to the ECRH stray fields and at the same time generates the necessary
      reference signal. Electromagnetic simulations and laboratory tests were performed
      to validate the proposed solution and are compared with the in-vessel calibration
      tests.

PMID- 23130803
TI  - Upgrade of the JET far infrared interferometer diagnostic.
AB  - In recent years there has been a major upgrade of the JET far infrared diagnostic
      system consisting of a new laser system with the wavelength at 118.8 MUm at and
      more advanced processing electronics for phase counting. This provides a second
      colour measurement of the electron plasma density on the vertical system. Due to
      the shorter wavelength, the plasma induced laser beam refraction is reduced by a
      factor of three alleviating density errors caused by loss of signal (so-called
      "fringe jumps" [A. Murari et al., Rev. Sci. Instrum. 77, 073505 (2006)]), in
      particular during high performance plasmas experiments in JET.

PMID- 23130804
TI  - Introducing minimum Fisher regularisation tomography to AXUV and soft x-ray
      diagnostic systems of the COMPASS tokamak.
AB  - The contribution focuses on plasma tomography via the minimum Fisher
      regularisation (MFR) algorithm applied on data from the recently commissioned
      tomographic diagnostics on the COMPASS tokamak. The MFR expertise is based on
      previous applications at Joint European Torus (JET), as exemplified in a new case
      study of the plasma position analyses based on JET soft x-ray (SXR) tomographic
      reconstruction. Subsequent application of the MFR algorithm on COMPASS data from
      cameras with absolute extreme ultraviolet (AXUV) photodiodes disclosed a peaked
      radiating region near the limiter. Moreover, its time evolution indicates
      transient plasma edge cooling following a radial plasma shift. In the SXR data,
      MFR demonstrated that a high resolution plasma positioning independent of the
      magnetic diagnostics would be possible provided that a proper calibration of the
      cameras on an x-ray source is undertaken.

PMID- 23130805
TI  - Improving the homogeneity of tissue-mimicking cryogel phantoms for medical
      imaging.
AB  - PURPOSE: Tissue-mimicking phantoms can help in uncovering potential weaknesses in
      medical imaging systems. This work presents a new approach to developing phantoms
      for magnetic resonance elastography (MRE). Elastography requires sufficiently
      large and well-characterized phantoms to accurately validate motion estimation
      methods and to provide accurate stiffness measurements. Physically crosslinked
      polyvinyl alcohol hydrogels, prepared by the freeze-thaw technique, have been
      extensively used as MRE phantoms. However, the large cryogels developed by this
      technique usually exhibit variations in properties due to the low thermal
      conductivity of the polymeric solution. This leads to variations in freezing
      thawing rates across the gels. Therefore, designing homogeneous large cryogels
      with tissue-mimicking mechanical properties poses a challenge to medical imaging
      researchers. METHODS: Unlike conventional freeze-thaw techniques that use either
      sudden freezing or ramp freezing, the authors have developed a modified freeze
      thaw process featuring a combination of multiple ramps and isotherms within a
      single freeze-thaw cycle. Aiming to develop brain-mimicking phantoms, they have
      blended three different water-soluble polymers (polyvinyl pyrrolidone, agarose,
      and polyacrylic acid) with polyvinyl alcohol and produced cryogels with a wide
      range of mechanical properties and swelling characteristics. The effect of the
      modified process on mechanical properties, swelling, and melting enthalpy of the
      produced gels has been investigated in this study. RESULTS: It was demonstrated
      that imposing additional isotherms at the vicinity of phase change temperatures
      could effectively reduce the variations in properties within a typical large
      phantom (diameter vs height: 100 mm * 100 mm). While the conventional freeze-thaw
      process resulted in ~16% variation in the enthalpy of fusion across the produced
      gels, the modified process reduced this variation to below 8%. The homogeneity in
      mechanical properties was also improved by over 50% compared to the conventional
      process. Upon comparing the mechanical properties of the gels with those of brain
      white matter, the authors have shown that a blend of polyvinyl alcohol and
      polyvinyl pyrrolidone can provide brain-mimicking properties, while leading to
      stable gels. CONCLUSIONS: The modified freeze-thaw process enabled to minimize
      the temperature gradient within the large cryogel phantoms during the freeze-thaw
      cycle. The results of this study can help to fill the gaps in the scientific
      literature with regard to developing homogeneous phantoms for medical imaging.
      This work also provides a solid foundation for future studies in this field and
      could facilitate formulating new hydrogels to replicate the viscoelastic
      properties of soft tissues.

PMID- 23130806
TI  - Mediators of the effect of the JUMP-in intervention on physical activity and
      sedentary behavior in Dutch primary schoolchildren from disadvantaged
      neighborhoods.
AB  - BACKGROUND: Important health benefits can be achieved when physical activity in
      children from low socio-economic status is promoted and sedentariness is limited.
      By specifying the mediating mechanisms of existing interventions one can improve
      future physical activity interventions. This study explored potential mediators
      of the long-term effect of the school-based multicomponent JUMP-in intervention
      on sport participation, outdoor play and screen time in Dutch primary
      schoolchildren from disadvantaged neighborhoods. METHODS: In total, 600 primary
      schoolchildren (aged 9.8 +/- 0.7, 51% girls, 13% Dutch ethnicity, 35% overweight)
      from 9 intervention and 10 control schools were included in the analyses. JUMP-in
      was developed using Intervention Mapping, and targeted psychological and
      environmental determinants of physical activity. Outcome behaviors were self
      reported sport participation, outdoor play, TV-viewing behavior and computer use.
      Potential mediators were self-reported psychological, social and physical
      environmental factors. RESULTS: JUMP-in was effective in improving sport
      participation after 20 months, but not in improving outdoor play, or reducing TV
      viewing or computer time. JUMP-in was not effective in changing hypothesized
      mediators so no significant mediated effects could be identified. However,
      changes in self-efficacy, social support and habit strength were positively
      associated with changes in sport participation, and changes in social support,
      self-efficacy, perceived planning skills, enjoyment and habit strength were
      positively associated with changes in outdoor play. Changes in enjoyment was
      positively associated with changes in TV-viewing while parental rules were
      negatively associated. Having a computer in the bedroom and enjoyment were
      positively associated with changes in computer use, while changes in parental
      rules were negatively associated. CONCLUSIONS: Besides a significant positive
      effect on sports participation, no significant intervention effect on outdoor
      play, screen time or any of the potential mediators was found. This suggest that
      other (unmeasured) factors operated as mediating mechanisms of the intervention,
      that we used unsuccessful intervention strategies, that the strategies were
      inappropriately implemented, or that children are unable to accurately recall
      past activities and cognitions. Additionally, the school setting might not be the
      sole channel to influence leisure time activities. Still, several personal and
      environmental constructs were found to be relevant in predicting change in sport
      participation, outdoor play and screen behavior and seem to be potential
      mediators. Future interventions are recommended including more effective
      strategies targeting these relevant constructs, addressing different constructs
      (e.g. pedagogic skills of parents), and focusing on different implementation
      settings. TRIAL REGISTRATION: [corrected] ISRCTN17489378.

PMID- 23130807
TI  - Thyroid carcinoma and primary amenorrhea due to Mayer-Rokitansky-Kuster-Hauser
      syndrome: a case report.
AB  - INTRODUCTION: This case report describes an association between an exceptionally
      rare congenital anomaly and differentiated thyroid carcinoma. Mayer-Rokitansky
      Kuster-Hauser syndrome is characterized by vaginal aplasia associated with other
      Mullerian duct abnormalities. Its penetrance varies, as does the involvement of
      other organs. The association with thyroid carcinoma appears to be exceptionally
      rare, and warrants further attention. CASE PRESENTATION: We present the case of a
      19-year-old Caucasian woman with amenorrhea and thyroid disease, with an
      unusually late diagnosis of gynecological abnormality. Management of her
      amenorrhea included investigation for congenital anomalies, including Mayer
      Rokitansky-Kuster-Hauser syndrome. Endocrine evaluation included a detailed
      analysis of sex hormone levels and thyroid function. The results of a physical
      examination and neck ultrasonography revealed abnormalities of the thyroid gland,
      which led to a diagnosis of thyroid cancer. To the best of our knowledge, thyroid
      cancer has not previously been reported in association with Mayer-Rokitansky
      Kuster-Hauser syndrome. However, genetic links between Mayer-Rokitansky-Kuster
      Hauser syndrome and thyroid cancer have not been investigated. The association
      may therefore be coincidental. CONCLUSIONS: All women with primary amenorrhea
      should undergo complete investigation of the genital tract and the endocrine
      axis. Careful examination of the thyroid gland is recommended.

PMID- 23130809
TI  - How do people with borderline personality disorder respond to norm violations?
      Impact of personality factors on economic decision-making.
AB  - Research suggests that patients with borderline personality disorder (BPD)
      experience profound difficulties in relationships. These difficulties reside, in
      part, in patients' tendency to overattribute negative emotions to self and others
      and in behaviors that are consistent with an opportunistic interpersonal
      orientation, as well as pathological identification mechanisms. Accordingly, the
      present study sought to examine the relationship between personality traits and
      behavior in BPD using an economic game designed to elicit participants'
      egocentric versus altruistic attitudes. Thirty patients with BPD performed a
      Dictator Game with the option to punish observed unfair behavior. Personality
      traits were measured using the NEO-FFI and the Mach-IV Scale. For comparison, 30
      matched nonclinical subjects were recruited. BPD patients scored significantly
      higher on Neuroticism and Machiavellianism. Conversely, patients had lower scores
      on Agreeableness, Extraversion, and Conscientiousness than controls. While high
      Machiavellianism and low Agreeableness were associated with selfish behavior in
      the control group, the opposite was found in BPD. Inverse correlations of
      Extraversion and Openness with the degree of costly punishment were present only
      in the BPD group; moreover, Neuroticism correlated positively with the degree of
      punishment in BPD patients. The motivation for costly punishment differs between
      BPD patients and controls. The behavior observed in BPD can be interpreted as
      "angry retaliation" by means of identification with the victim's perspective, but
      does not seem to be altruistically motivated. 

PMID- 23130813
TI  - Emotional reactivity to social rejection and negative evaluation among persons
      with borderline personality features.
AB  - The present study examined the emotional reactivity of persons with heightened
      borderline personality (BP) features to social rejection and negative evaluation
      in the laboratory. Individuals with high levels of BP features (n = 30) and
      controls with low levels of BP features (n = 44) were randomly assigned to a
      condition involving negative evaluation based on writing (negative
      evaluation/academic), or a condition involving negative evaluation based on
      personal characteristics as well as social rejection (negative evaluation/social
      rejection). Hypothesis 1 was that high-BP individuals, but not low-BP controls,
      would show greater emotional reactivity to the negative evaluation/social
      rejection stressor, compared with the negative evaluation/academic (writing)
      stressor. Hypothesis 2 was that high-BP individuals would specifically show
      greater reactivity of shame- and anger-related emotions to the negative
      evaluation/social rejection stressor compared with the negative
      evaluation/academic stressor. Findings indicated that high-BP individuals showed
      heightened emotional reactivity to the social rejection stressor but not to the
      negative evaluation stressor, but the opposite pattern occurred for controls. In
      addition, there was evidence for heightened reactivity of irritability, distress,
      and shame for the high-BP group, specifically in the social rejection condition. 

PMID- 23130814
TI  - Differences between axes depend on where you set the bar: associations among
      symptoms, interpersonal relationship and alexithymia with number of personality
      disorder criteria.
AB  - Personality disorders are better understood as entities that vary according to
      severity along specific domains rather than a phenomenon separate from and
      unrelated to Axis I disorders. This study explores whether patients who were
      rated as having greater numbers of personality disorder traits reported greater
      levels of interpersonal problems, psychiatric symptoms, and alexithymia. The
      sample was composed of 506 consecutive patients assessed in a private outpatient
      center who were administered the SCID-II Symptom-Checklist (SCL-90-R), Inventory
      of Interpersonal Problems (IIP-47), and Toronto Alexithymia-Scale (TAS-.20).
      Based upon the number of personality disorder traits identified in the SCID,
      participants were classified into five groups: 0-4, 5-9, 10-14, 15-19, and 20 or
      more personality disorder traits met. Comparisons between groups revealed that
      symptom severity and levels of interpersonal problems increased between groups as
      the number of personality disorder traits increased. After covarying for symptom
      severity, there were no significant between-groups differences for levels of
      alexithymia. Findings are consistent with the claims that the simple Axis I-Axis
      II distinction is not an optimal strategy to understand personality pathology. It
      instead may be more fruitful to consider group differences in terms of numbers of
      personality disorder traits met.

PMID- 23130816
TI  - Placental villous hypermaturation is associated with idiopathic preterm birth.
AB  - OBJECTIVE: Pregnancy complications such as intra-amniotic infection,
      preeclampsia, and fetal intrauterine growth restriction (IUGR) account for most
      cases of preterm birth (PTB), but many spontaneous PTB cases do not have a clear
      etiology. We hypothesize that placental insufficiency may be a potential cause of
      idiopathic PTB. METHODS: Secondary analysis of 82 placental samples from women
      with PTB obtained from a multicenter trial of repeat versus single antenatal
      corticosteroids. Samples were centrally reviewed by a single placental
      pathologist masked to clinical outcomes. The histopathologic criterion for
      infection was the presence of acute chorioamnionitis defined as neutrophils
      marginating into the chorionic plate. Placental villous hypermaturation (PVH) was
      defined as a predominance of terminal villi (similar to term placenta) with
      extensive syncytial knotting. Idiopathic PTB comprised a group without another
      known etiology such as preeclampsia, IUGR or infection. RESULTS: Acute
      chorioamnionitis was observed in 33/82 (40%) cases. Other known causes of PTB
      were reported in 18/82 (22%). The remaining 31/82 (38%) were idiopathic. The
      frequency of PVH in idiopathic PTB (26/31 = 84%) was similar to cases with IUGR
      or preeclampsia (16/18 = 89%), but significantly more common than PVH in the
      group with acute chorioamnionitis (10/33 = 30%) (p < 0.001). CONCLUSIONS: PVH,
      which is a histologic marker of relative placental insufficiency, is a common
      finding in idiopathic PTB.

PMID- 23130817
TI  - Significant reduction of homocysteine level with multiple B vitamins in atrophic
      glossitis patients.
AB  - OBJECTIVE: This study evaluated whether supplementations of different vitamins
      and iron could reduce the serum homocysteine levels in 91 atrophic glossitis (AG)
      patients. MATERIALS AND METHODS: Atrophic glossitis (AG) patients with
      concomitant deficiencies of vitamin B12 only (n = 39, group I), folic acid only
      (n = 10, group II), iron only (n = 9, group III), or vitamin B12 plus iron (n =
      19, group IV) were treated with vitamin BC capsules plus deficient hematinics. AG
      patients without definite hematinic deficiencies (n = 14, group V) were treated
      with vitamin BC capsules only. The blood homocysteine and hematinic levels at
      baseline and after treatment till all oral symptoms had disappeared were measured
      and compared by paired t-test. RESULTS: Supplementations with vitamin BC capsules
      plus corresponding deficient hematinics for groups I, II, III, IV patients and
      with vitamin BC capsules only for group V patients could reduce the high serum
      homocysteine levels to significantly lower levels after a mean treatment period
      of 8.3-11.6 months (all P-values < 0.05). CONCLUSION: Supplementations with
      vitamin BC capsules plus corresponding deficient hematinics or with vitamin BC
      capsules only can reduce the high serum homocysteine levels to significantly
      lower levels in AG patients.

PMID- 23130818
TI  - Mortality in members of HIV-1 serodiscordant couples in Africa and implications
      for antiretroviral therapy initiation: results of analyses from a multicenter
      randomized trial.
AB  - BACKGROUND: The risk of HIV-1 related mortality is strongly related to CD4 count.
      Guidance on optimal timing for initiation of antiretroviral therapy (ART) is
      still evolving, but the contribution of HIV-1 infection to excess mortality at
      CD4 cell counts above thresholds for HIV-1 treatment has not been fully
      described, especially in resource-poor settings. To compare mortality among HIV-1
      infected and uninfected members of HIV-1 serodiscordant couples followed for up
      to 24 months, we conducted a secondary data analysis examining mortality among
      HIV-1 serodiscordant couples participating in a multicenter, randomized
      controlled trial at 14 sites in seven sub-Saharan African countries. METHODS:
      Predictors of death were examined using Cox regression and excess mortality by
      CD4 count and plasma HIV-1 RNA was computed using Poisson regression for
      correlated data. RESULTS: Among 3295 HIV serodiscordant couples, we observed 109
      deaths from any cause (74 deaths among HIV-1 infected and 25 among HIV-1
      uninfected persons). Among HIV-1 infected persons, the risk of death increased
      with lower CD4 count and higher plasma viral levels. HIV-1 infected persons had
      excess mortality due to medical causes of 15.2 deaths/1000 person years at CD4
      counts of 250 - 349 cells/MUl and 8.9 deaths at CD4 counts of 350 - 499
      cells/MUl. Above a CD4 count of 500 cells/MUl, mortality was comparable among HIV
      1 infected and uninfected persons. CONCLUSIONS: Among African serodiscordant
      couples, there is a high rate of mortality attributable to HIV-1 infection at CD4
      counts above the current threshold (200 - 350 cells/MUl) for ART initiation in
      many African countries. These data indicate that earlier initiation of treatment
      is likely to provide clinical benefit if further expansion of ART access can be
      achieved. TRIAL REGISTRATION: Clinicaltrials.gov (NCT00194519).

PMID- 23130819
TI  - What is your diagnosis? Bronchoalveolar lavage and cerebrospinal fluid from a dog
      in Italy.

PMID- 23130820
TI  - Analytical thresholds and sensitivity: establishing RFU thresholds for forensic
      DNA analysis.
AB  - Determining appropriate analytical thresholds (ATs) for forensic DNA analysis is
      critical to maximize allele detection. In this study, six methods to determine
      ATs for forensic DNA purposes were examined and compared. Four of the methods
      rely on analysis of the baseline noise of a number of negatives, while two
      utilize the relationship between relative fluorescence unit signal and DNA input
      in the polymerase chain reaction (PCR) derived from a dilution series ranging
      from 1 to 0.06 ng. Results showed that when a substantial mass of DNA (i.e., >1
      ng) was amplified, the baseline noise increased, suggesting the application of an
      AT derived from negatives should only be applied to samples with low levels of
      DNA. Further, the number and intensity of these noise peaks increased with
      increasing injection times, indicating that to maximize the ability to detect
      alleles, ATs should be validated for each post-PCR procedure employed.

PMID- 23130821
TI  - Low suspicion lesions on multiparametric magnetic resonance imaging predict for
      the absence of high-risk prostate cancer.
AB  - What's known on the subject? and What does the study add? Over-treatment of
      indolent prostate cancer lesions is a problem which can result in increased human
      and medical costs. Lesions with a low suspician level at mpMRI of the prostate
      have low risk of including high risk prostate cancer. OBJECTIVE: To determine
      whether multiparametric magnetic resonance imaging (mpMRI) has the potential to
      identify patients at low risk for cancer, thus obviating the need for biopsy.
      Prostate cancer is currently diagnosed by random biopsies, resulting in the
      discovery of multiple low-risk cancers that often lead to overtreatment. PATIENTS
      AND METHODS: We reviewed 800 consecutive patients who underwent a 3 Tesla mpMRI
      of the prostate with an endorectal coil from March 2007 to November 2011. All
      suspicious lesions were independently reviewed by two radiologists using T2
      weighted, diffusion-weighted, spectroscopic and dynamic contrast-enhanced MRI
      sequences. Patients with only low suspicion lesions (maximum of two positive
      parameters on mpMRI) who subsequently underwent transrectal ultrasonography
      (TRUS)/MRI fusion targeted biopsy were selected for analysis. RESULTS: In total,
      125 patients with only low suspicion prostatic lesions on mpMRI were identified.
      On TRUS/MRI fusion biopsy, 77 (62%) of these patients had no cancer detected, 38
      patients had Gleason 6 disease and 10 patients had Gleason 7 (3+4) disease. There
      were 30 patients with cancer detected on biopsy who qualified for active
      surveillance using 2011 National Comprehensive Cancer Network guidelines. No
      cases of high-risk (>= Gleason 4+3) cancer were identified on biopsy and, of the
      fifteen patients who underwent radical prostatectomy at our institution, none
      were pathologically upgraded to high-risk cancer. Thus, for patients with only
      low suspicion lesions, 107 (88%) patients either had no cancer or clinically
      insignificant disease. CONCLUSIONS: The results obtained in the present study
      show that low suspicion lesions on mpMRI are associated with either negative
      biopsies or low-grade tumours suitable for active surveillance. Such patients
      have a low risk of harbouring high-risk prostate cancers.

PMID- 23130822
TI  - Fire on an intensive care unit caused by an oxygen cylinder.

PMID- 23130823
TI  - {Ta12}/{Ta16} cluster-containing polytantalotungstates with remarkable
      photocatalytic H2 evolution activity.
AB  - Four novel polytantalotungstates K(5)Na(4)[P(2)W(15)O(59)(TaO(2))(3)].17H(2)O
      (1), K(8)Na(8)H(4)[P(8)W(60)Ta(12)(H(2)O)(4)(OH)(8)O(236)].42H(2)O (2),
      Cs(3)K(3.5)H(0.5)[SiW(9)(TaO(2))(3)O(37)].9H(2)O (3), and
      Cs(10.5)K(4)H(5.5)[Ta(4)O(6)(SiW(9)Ta(3)O(40))(4)].30H(2)O (4) were synthesized.
      Compounds 1 and 3 are tris-(peroxotantalum)-substituted Dawson- and Keggin-type
      derivatives, whereas 2 and 4 are tetrameric oligomers containing respectively an
      unprecedented {Ta(12)} and {Ta(16)} cluster core. The photocatalytic activities
      of 2 and 4 for H(2) evolution from water were evaluated. The significantly
      enhanced performance against the control K(6)[P(2)W(18)O(62)] can be attributed
      to the modulation of the electronic structures of these novel POMs by Ta
      incorporation. The highest activity observed so far with the use of 2 can be
      further rationalized by the presence of distorted heptacoordinate Ta atoms in the
      form of TaO(7) pentagonal bipyramid.

PMID- 23130824
TI  - Robustness of circadian timing systems evolves in the fruit fly Drosophila
      melanogaster as a correlated response to selection for adult emergence in a
      narrow window of time.
AB  - Robustness is a fundamental property of biological timing systems that is likely
      to ensure their efficient functioning under a wide range of environmental
      conditions. Here we report the findings of our study aimed at examining
      robustness of circadian clocks in fruit fly Drosophila melanogaster populations
      selected to emerge as adults within a narrow window of time. Previously, we have
      reported that such flies display enhanced synchrony, accuracy, and precision in
      their adult emergence and activity/rest rhythms. Since it is expected that
      accurate and precise circadian clocks may confer enhanced stability in circadian
      time-keeping, we decided to examine robustness in circadian rhythms of flies from
      the selected populations by subjecting them to a variety of environmental
      conditions comprising of a range of photoperiods, light intensities, ambient
      temperatures, and constant darkness. The results revealed that adult emergence
      and activity/rest rhythms of flies from the selected stocks were more robust than
      controls, as they displayed enhanced stability under a wide variety of
      environmental conditions. These results suggest that selection for adult
      emergence within a narrow window of time results in the evolution of robustness
      in circadian timing systems of the fruit fly D. melanogaster.

PMID- 23130826
TI  - Epigenetics and the developmental origins of disease: the key to unlocking the
      door of personalized medicine.

PMID- 23130825
TI  - Catalytic mechanism and product specificity of oxidosqualene-lanosterol cyclase:
      a QM/MM study.
AB  - Oxidosqualene-lanosterol cyclase (OSC) is a key enzyme in the biosynthesis of
      cholesterol. The catalytic mechanism and the product specificity of OSC have
      herein been studied using QM/MM calculations. According to our calculations, the
      protonation of the epoxide ring of oxidosqualene is rate-limiting. Wild-type OSC
      (which generates lanosterol), and the mutants H232S (which generates parkeol) and
      H232T (which generates protosta-12,24-dien-3-beta-ol) were modeled, in order to
      explain the product specificity thereof. We show that the product specificity of
      OSC at the hydride/methyl-shifting stage is unlikely to be achieved by the
      stabilization of the cationic intermediates, as the precursor of lanosterol is in
      fact not the most stable cationic intermediate for wild-type OSC. The energy
      barriers for the product-determining conversions are instead found to be related
      to the product specificity of different OSC mutants, and we thus suggest that the
      product specificity of OSC is likely to be controlled by kinetics, rather than
      thermodynamics.

PMID- 23130829
TI  - The role of epigenetic inheritance in stress regulation.

PMID- 23130827
TI  - Implications of epigenetic mechanisms for vascular development and disease.

PMID- 23130830
TI  - Conference Scene: Epigenetic regulation: from mechanism to intervention.
AB  - The Medical Research Council Clinical Sciences Centre Symposium on Epigenetic
      Regulation: From Mechanism to Intervention in London, UK, which was held on 20-22
      June 2012, attracted 305 participants from around the globe and included 37
      speakers and 85 selected poster presentations. The organizing committee, led by
      Niall Dillon of the Medical Research Council Clinical Sciences Centre (London,
      UK), consisted of several distinguished researchers in the fields of epigenetics
      and chromatin organization from across the UK. The meeting covered a diverse
      range of topics and brought together scientists carrying out fundamental research
      on epigenetic mechanisms and also researchers who are exploring the role of
      epigenetics in human diseases and its clinical applications. In addition, the
      meeting highlighted some emerging aspects in the rapidly evolving field of
      epigenetics.

PMID- 23130831
TI  - Epigenetic profile in chronic lymphocytic leukemia using methylation-specific
      multiplex ligation-dependent probe amplification.
AB  - AIM: To analyze the methylation status of 35 tumor suppressor genes using
      methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA)
      in chronic lymphocytic leukemia (CLL). MATERIALS & METHODS: The DNA of 37 samples
      from patients with CLL, six healthy donors, and Jurkat and Ramos cell lines was
      analyzed by MS-MLPA. RESULTS: Our results confirm that hypermethylation is a
      common and not randomly distributed event in CLL, and some genes, such as WT1,
      CDH13, IGSF4/TSLC1, GATA5, DAPK1 and RARB, are hypermethylated in more than 25%
      of the analyzed samples. Importantly, MS-MLPA also detected hypermethylation of
      some genes not reported previously in CLL, and their methylation status was
      confirmed by bisulfite sequencing. CONCLUSION: These results indicate that MS
      MLPA is a useful technique for the detection of methylation in CLL samples.
      Selecting CLL-specific methylation targets in order to generate a CLL-specific MS
      MLPA probe set could enhance its usefulness as a tool in studies of risk
      stratification and guiding the best therapeutic decision.

PMID- 23130833
TI  - Using epigenome-wide association scans of DNA methylation in age-related complex
      human traits.
AB  - With rapid technological advancements emerging epigenetic studies of complex
      traits have shifted from candidate gene analyses towards epigenome-wide
      association studies (EWAS). EWAS aim to systematically identify epigenetic
      variants across the genome that associate with complex phenotypes. Recent EWAS
      using case-control and disease-discordant identical twin designs have identified
      phenotype-associated differentially methylated regions for several traits.
      However, EWAS still face many challenges related to methodology, design and
      interpretation, owing to the dynamic nature of epigenetic variants over time.
      This article reviews analytical considerations in conducting EWAS and recent
      applications of this approach to human aging and age-related complex traits.

PMID- 23130834
TI  - Epigenetic implication of gene-adjacent retroelements in Helicobacter pylori
      infected adults.
AB  - A chronic inflammatory condition of gastric mucosa can facilitate the influx of
      new stem cells into the stomach. Epigenetic codes, such as DNA methylation, may
      be responsible for the stable maintenance of epigenetic phenotypes established in
      the new stomach-adapted stem cells. A number of hypotheses have been made for the
      role of CpG-island methylation, which is common in the Helicobacter pylori
      infected stomach. However, they could not explain the plausible role of CpG
      island methylation in the re-establishment of epigenetic phenotypes. These
      islands are highly repetitive sequences densely methylated throughout the human
      genome, the so-called parasitic retroelements, which expand a number of cDNA
      copies with reverse transcriptase. The densely methylated retroelements adjacent
      to the host genes can form the transitional-CpG sites around gene-control regions
      that are barely methylated. This review focuses on the putative role of
      transitional CpG methylation in the adaptive differentiation of new stem cells in
      the H. pylori-infected stomach.

PMID- 23130835
TI  - Chromatin regulators with tumor suppressor properties and their alterations in
      human cancers.
AB  - Key components of the cell epigenome include DNA CpG methylation profile and
      chromatin modification patterns. Chromatin regulators act as master controllers
      of gene transcription in normal cells through regulation of histone modifications
      and chromatin remodeling. During human cancer pathogenesis, the functions of
      chromatin regulators are frequently disrupted by genetic mutations and/or
      epigenetic alterations, causing perturbation of broad or even genome-wide scale
      gene-expression profiles. Thus, histone-modifying and chromatin-remodeling genes
      can be taken as critical 'cancer genes'. This review summarizes the current
      knowledge on chromatin regulators with tumor suppressor properties, as well as
      their aberrant alterations in human cancers.

PMID- 23130832
TI  - Epigenetic genome-wide association methylation in aging and longevity.
AB  - The aging phenotype is the result of a complex interaction between genetic,
      epigenetic and environmental factors. Evidence suggests that epigenetic changes
      (i.e., a set of reversible, heritable changes in gene function or other cell
      phenotype that occurs without a change in DNA sequence) may affect the aging
      process and may be one of the central mechanisms by which aging predisposes to
      many age-related diseases. The total number of altered methylation sites
      increases with increasing age, such that they could serve as marker for
      chronological age. This article systematically highlights the advances made in
      the field of epigenomics and their contribution to the understanding of the
      complex physiology of aging, lifespan and age-associated diseases.

PMID- 23130837
TI  - The dysfunctional placenta epigenome: causes and consequences.
AB  - The placenta is a fetal-maternal endocrine organ responsible for ensuring proper
      fetal development throughout pregnancy. Adverse insults to the intrauterine
      environment often lead to expression level changes in placental genes, many of
      which are epigenetically regulated by DNA methylation, histone modifications and
      ncRNA interference. These epigenetic alterations may cause placental dysfunction,
      resulting in offspring of low birthweight owing to adverse pregnancy
      complications such as intrauterine growth restriction. Numerous epidemiological
      studies have shown a strong correlation between low birthweight and increased
      risk of developing metabolic diseases and neurological imbalances in adulthood,
      and in subsequent generations, indicating that epigenetic regulation of gene
      expression can be propagated stably with long-term effects on health. This
      article provides an overview of the various environmental factors capable of
      inducing detrimental changes to the placental epigenome, as well as the
      corresponding mechanisms that prime the offspring for onset of disease later in
      life.

PMID- 23130836
TI  - Blood chromatin as a biosensor of the epigenetic milieu: a tool for studies in
      living psychiatric patients.
AB  - This article constructs an argument for using blood chromatin (contained in
      nucleated blood cells) as a protein biosensor to integrate the ambient epigenetic
      influences in the internal milieu. An analogy is made to blood glycated
      hemoglobin (HbA1c) in diabetes as an integrated proxy for glucose levels and body
      wide protein glycation. Genome-wide chromatin can serve as an organizing
      principle that bridges the central and peripheral compartments by entraining
      commensurable gene networks. Chromatin deposition along these networks will be
      imposed by the totality of epigenetic influences, which incorporates significant
      contributions from biochemicals that readily traverse the blood-brain barrier. In
      a clinical trial, these influences would be dominated by pharmaceuticals designed
      to override pathophysiological signals. In practice, mRNA readouts would be
      limited to nonsynaptic gene networks whose critical nodes are occupied by a site
      specific chromatin modification. Finally, chromatin measurements in peripheral
      tissue will retain the influences of a patient's lifestyle and unique genomic
      background.

PMID- 23130838
TI  - A focus on the preclinical development and clinical status of the histone
      deacetylase inhibitor, romidepsin (depsipeptide, Istodax((r))).
AB  - Romidepsin (Istodax((r)), depsipeptide, FR901228, FK228, NSC 630176) is a cyclic
      peptide, broad-spectrum, potent histone deacetylase inhibitor, with activity
      mainly against class I histone deacetylase enzymes. In this article, we give an
      overview of the putative modes of action, such as effects on gene expression,
      cell cycle regulation, apoptosis induction, DNA repair, protein acetylation and
      induction of autophagy. Romidepsin has mainly been developed as a therapy for
      hematologic malignancies and is approved by the US FDA for the treatment of
      cutaneous T-cell lymphomas. This report outlines the laboratory and clinical
      development of the compound as a single agent that has more recently been
      evaluated in combination with other anticancer therapeutics, such as proteasome
      inhibitors.

PMID- 23130840
TI  - Regioselective radical arylation of anilines with arylhydrazines.
AB  - Substituted 2-aminobiphenyls have been prepared from arylhydrazines and anilines
      via radical arylation reactions under simple oxidative conditions. The strong
      directing effect of the free and unprotonated amino functionality leads to high
      regioselectivities, and anilines have been shown to be significantly better aryl
      radical acceptors than nitrobenzenes or phenyl ethers. The methodology is also
      applicable to phenols, which react best as phenolates under strongly basic
      conditions. Finally, radical arylation reactions of anilines and anilinium salts
      under various conditions have for the first time demonstrated that
      regioselectivity can also be controlled through the rearomatization step and that
      the addition of an aryl radical to a substituted benzene might even be
      reversible.

PMID- 23130841
TI  - Severe bleeding tendency caused by a rare complication of excessive fibrinolysis
      with disseminated intravascular coagulation in a 51-year-old Japanese man with
      prostate cancer: a case report.
AB  - INTRODUCTION: Disseminated intravascular coagulation causes thrombotic tendency
      leading to multiple organ failure and occurs in a wide variety of diseases
      including malignancy. Disseminated intravascular coagulation is a latent
      complication in people with prostate cancer. CASE PRESENTATION: A 51-year-old
      Japanese man with advanced castration-resistant prostate cancer was admitted to
      our hospital because of extensive purpura and severe anemia. Prolonged plasma
      coagulation time, hypofibrinogenemia and normal platelet count suggested that a
      decrease in fibrinogen induced a bleeding tendency causing purpura. However,
      elevated plasma levels of thrombin-antithrombin complex, fibrin and/or fibrinogen
      degradation products and D-dimers, with positive fibrin monomer test, manifested
      disseminated intravascular coagulation and subsequent fibrinolysis. Plasma levels
      of thrombin-antithrombin complex, fibrin and/or fibrinogen degradation products
      and D-dimers decreased after administration of low-molecular-weight heparin.
      However, low fibrinogen and alpha2-antiplasmin levels were not improved and
      plasmin-antiplasmin complex did not decrease, which revealed excessive
      fibrinolysis complicated with disseminated intravascular coagulation. We
      suspected that prostate cancer cell-derived urokinase-type plasminogen activator
      caused excessive fibrinolysis. Administration of tranexamic acid for
      fibrinogenolysis was added together with high-dose anti-androgen therapy
      (fosfestrol) for prostate cancer. Thereafter, prostate-specific antigen and
      plasmin-antiplasmin complex decreased, followed by normalized fibrinogen and
      alpha2-antiplasmin levels, and the patient eventually recovered from the bleeding
      tendency. Immunohistochemical staining of the biopsied prostate tissue exhibited
      that the prostate cancer cells produced tissue factor, the coagulation initiator,
      and urokinase-type plasminogen activator. CONCLUSION: This patient with rare
      complications of disseminated intravascular coagulation and excessive
      fibrinolysis is a warning case of potential coagulation disorder onset in
      patients with prostate cancer. We propose that combined administration of
      tranexamic acid and low-molecular-weight heparin together with high-dose anti
      androgen therapy is a useful therapeutic option for patients with this
      complicated coagulation disorder.

PMID- 23130842
TI  - Identification of the novel HLA-B*40:221 allele in a Taiwanese hematopoietic stem
      cell donor using a sequence-based typing method.
AB  - Using DNA sequence-based typing method, we found a new HLA-B*40 variant,
      B*40:221, in a Taiwanese hematopoietic stem cell donor. The allele sequence of
      B*40:221 is identical to the sequence of B*40:01:01 in exons 2, 3 and 4 except
      the nucleotides at codon 265 (GGG->AGG). The sequence variation caused one amino
      acid exchange at residue 265 where Gly was replaced by Arg. The probable HLA-A, 
      B, -C, -DRB1 and -DQB1 haplotype in association with B*40:221 may be deduced as
      HLA-A*11:01-B*40:221-C*03:04-DRB1*14:54-DQB1*05:02. The generation of B*40:221 is
      thought as a result of a nucleotide point mutation involving B*40:01:01. Our
      discovery of B*40:221 increases the polymorphism of B*40 in Taiwanese. 

PMID- 23130843
TI  - Nanoscale triboelectric-effect-enabled energy conversion for sustainably powering
      portable electronics.
AB  - Harvesting energy from our living environment is an effective approach for
      sustainable, maintenance-free, and green power source for wireless, portable, or
      implanted electronics. Mechanical energy scavenging based on triboelectric effect
      has been proven to be simple, cost-effective, and robust. However, its output is
      still insufficient for sustainably driving electronic devices/systems. Here, we
      demonstrated a rationally designed arch-shaped triboelectric nanogenerator (TENG)
      by utilizing the contact electrification between a polymer thin film and a metal
      thin foil. The working mechanism of the TENG was studied by finite element
      simulation. The output voltage, current density, and energy volume density
      reached 230 V, 15.5 MUA/cm(2), and 128 mW/cm(3), respectively, and an energy
      conversion efficiency as high as 10-39% has been demonstrated. The TENG was
      systematically studied and demonstrated as a sustainable power source that can
      not only drive instantaneous operation of light-emitting diodes (LEDs) but also
      charge a lithium ion battery as a regulated power module for powering a wireless
      sensor system and a commercial cell phone, which is the first demonstration of
      the nanogenerator for driving personal mobile electronics, opening the chapter of
      impacting general people's life by nanogenerators.

PMID- 23130844
TI  - The utility of the Hopkins Verbal Learning Test (Chinese version) for screening
      dementia and mild cognitive impairment in a Chinese population.
AB  - BACKGROUND: The Hopkins Verbal Learning Test (HVLT) has been validated for
      detecting dementia in English-speaking populations. However, no studies have
      examined the Chinese version of the HVLT scale, and appropriate cut-off scores
      for dementia in the Chinese population remain unclear. METHODS: 631 subjects aged
      60 and over were recruited at a memory clinic at Dongzhimen Hospital in Beijing.
      Of these, 249 were classified as exhibiting normal cognition (NC), 134 were
      diagnosed with mild cognitive impairment (MCI), 97 were diagnosed with
      Alzheimer's disease (AD), 14 met the diagnosis for vascular dementia (VaD), and
      50 were diagnosed with other types of dementia, including mixed dementia. The
      discriminative capacity of the HVLT total learning score, recognition score and
      total score were calculated to determine their sensitivity and specificity for
      detecting MCI, AD and other dementias, and various cut-off scores. RESULTS: HVLT
      scores were affected by age, education and sex. The HVLT total learning score
      exhibited an optimal balance between sensitivity and specificity using a cut-off
      score of 15.5 for distinguishing AD and other types of dementia from NC using the
      ROC curve, with sensitivity of 94.7% for distinguishing AD and all types of
      dementia, and specificity of 92.5% for detecting AD and 93.4% for detecting all
      types of dementias. We stratified the AD and MCI groups by age, and calculated
      the validity in each age group. In the 50-64 years age group, when the cutoff
      score was 18.5, the sensitivity of 0.955 and specificity of 0.921 were obtained
      for discriminating the NC and AD groups, and in the 65-80 years group, and
      optimal sensitivity and specificity values (0.948 and 0.925, respectively) were
      obtained with a cutoff score of 14.5. When the cutoff score was 21.5 in HVLT
      total recall, an optimal balance was obtained between sensitivity and specificity
      (69.1% and 70.7%, respectively) in distinguishing MCI from NC. CONCLUSION: A cut
      off score of 15.5 in the HVLT total learning score led to high discriminative
      capacity between the dementia and NC groups. This suggests that the HVLT total
      learning score can provide a useful tool for discriminating dementia, but not
      MCI, from NC in clinical and epidemiological practice.

PMID- 23130845
TI  - Disproportionate costs and charges for pediatric catheter ablation: supply and
      demand... or just supply?

PMID- 23130846
TI  - Resolution of autoimmune thrombocytopenia associated with raltegravir use in an
      HIV-positive patient.
AB  - About 10% of the human immunodeficiency virus (HIV) patients show
      thrombocytopenia. We describe the case of an HIV/HCV-positive patient whose
      autoimmune thrombocytopenia resolved with the addition of raltegravir to previous
      highly active antiretroviral therapy (HAART). It is noteworthy that the effect on
      platelet count appeared to be independent of viral load suppression, which was
      achieved with previous antiretroviral regimens. In fact, it has been suggested
      that the positive effect exerted by raltegravir on autoimmune diseases is due to
      its inhibition on herpes viruses, and hence on activation of endogenous human
      retroviruses. This consideration, if confirmed, could open new avenues in the
      treatment of autoimmune thrombocytopenia in the HIV setting. 

PMID- 23130847
TI  - Volatilization modeling of two herbicides from soil in a wind tunnel experiment
      under varying humidity conditions.
AB  - Volatilization of pesticides from the bare soil surface is drastically reduced
      when the soil is under dry conditions (i.e., water content lower than the
      permanent wilting point). This effect is caused by the hydrated mineral surfaces
      that become available as additional sorption sites under dry conditions. However,
      established volatilization models do not explicitly consider the hydrated mineral
      surfaces as an independent sorption compartment and cannot correctly cover the
      moisture effect on volatilization. Here we integrated the existing mechanistic
      understanding of sorption of organic compounds to mineral surfaces and its
      dependence on the hydration status into a simple volatilization model. The
      resulting model was tested with reported experimental data for two herbicides
      from a wind tunnel experiment under various well-defined humidity conditions. The
      required equilibrium sorption coefficients of triallate and trifluralin to the
      mineral surfaces, K(min/air), at 60% relative humidity were fitted to
      experimental data and extrapolated to other humidity conditions. The model
      captures the general trend of the volatilization in different humidity scenarios.
      The results reveal that it is essential to have high quality input data for
      K(min/air), the available specific surface area (SSA), the penetration depth of
      the applied pesticide solution, and the humidity conditions in the soil. The
      model approach presented here in combination with an improved description of the
      humidity conditions under dry conditions can be integrated into existing
      volatilization models that already work well for humid conditions but still lack
      the mechanistically based description of the volatilization process under dry
      conditions.

PMID- 23130848
TI  - Gold nanoparticle thin films fabricated by electrophoretic deposition method for
      highly sensitive SERS application.
AB  - We report an electrophoretic deposition method for the fabrication of gold
      nanoparticle (GNP) thin films as sensitive surface-enhanced Raman scattering
      (SERS) substrates. In this method, GNP sol, synthesized by a seed-mediated growth
      approach, and indium tin oxide (ITO) glass substrates were utilized as an
      electrophoretic solution and electrodes, respectively. From the scanning electron
      microscopy analysis, we found that the density of GNPs deposited on ITO glass
      substrates increases with prolonged electrophoresis time. The films possess high
      mechanical adhesion strength and exhibit strong localized surface plasmon
      resonance (LSPR) effect by showing high SERS sensitivity to detect 1 * 10-7 M
      rhodamine 6 G in methanol solution. Finally, the relationship between Raman
      signal amplification capability and GNP deposition density has been further
      investigated. The results of our experiment indicate that the high-density GNP
      film shows relatively higher signal amplification capability due to the strong
      LSPR effect in narrow gap regions between the neighboring particles on the film.

PMID- 23130849
TI  - Analysis of genetically modified red-fleshed apples reveals effects on growth and
      consumer attributes.
AB  - Consumers of whole foods, such as fruits, demand consistent high quality and seek
      varieties with enhanced health properties, convenience or novel taste. We have
      raised the polyphenolic content of apple by genetic engineering of the
      anthocyanin pathway using the apple transcription factor MYB10. These apples have
      very high concentrations of foliar, flower and fruit anthocyanins, especially in
      the fruit peel. Independent lines were examined for impacts on tree growth,
      photosynthesis and fruit characteristics. Fruit were analysed for changes in
      metabolite and transcript levels. Fruit were also used in taste trials to study
      the consumer perception of such a novel apple. No negative taste attributes were
      associated with the elevated anthocyanins. Modification with this one gene
      provides near isogenic material and allows us to examine the effects on an
      established cultivar, with a view to enhancing consumer appeal independently of
      other fruit qualities.

PMID- 23130850
TI  - Counting circadian cycles to determine the period of a circasemilunar rhythm in a
      marine insect.
AB  - Semilunar and lunar rhythms are often controlled endogenously, but the mechanisms
      of their respective free-run periods, when external factors are absent, are
      mostly unclear. In this investigation, the authors studied the mechanism
      controlling the period of the circasemilunar emergence rhythm of a marine midge,
      Pontomyia oceana, in southern Taiwan. Experimental approaches were adopted with
      various artificial light-dark (LD) periods, or T, from 22 to 28 h per cycle in
      the first experiment, and 18 to 30 h per cycle in the second experiment, as
      treatments on the same cohorts of midge larvae. The responses in emergence days
      were directly proportional to the magnitude of the treatments, just as that
      predicted by the frequency demultiplication hypothesis. A counting mechanism is
      thus the only hypothesis supported by this finding. To further test whether it is
      endogenous oscillations that are counted, submultiples as well as multiples of 24
      h, i.e., 6, 12, 24, and 48 h per cycle, were used as T. The midges under all
      these treatments emerged at similar days. This result supports the hypothesis
      that endogenous circadian oscillations, not external LD cycles, are counted in
      this circasemilunar emergence rhythm of the marine midge. This paper reports a
      first case supporting the frequency demultiplication hypothesis in a
      circasemilunar rhythm that is based on counting the cycles of endogenous
      circadian rhythms.

PMID- 23130851
TI  - Ionizing radiation in Crohn's disease.

PMID- 23130852
TI  - Ionizing radiation in patients with Crohn's disease. Estimation and associated
      factors.
AB  - INTRODUCTION: exposure to ionizing radiation is associated with an increased risk
      of developing tumors. Patients with Crohn's disease (CD) usually require multiple
      imaging tests using this type of radiation. OBJECTIVES: the objectives of this
      study were to estimate the total dose of ionizing radiation received by patients
      with Crohn's disease during their course and to identify the factors associated
      with higher radiation doses. METHODS: two hundred thirty-five CD patients
      diagnosed between 1972 and 2010 were included. The effective dose (ED) received
      by each patient was calculated retrospectively based on the number of
      gastrointestinal transit studies and computed tomography scans performed.
      Considering recent epidemiological studies, an ED greater than or equal to 50 mSv
      was used as the cut-off point for increased risk of developing cancer. RESULTS:
      the mean ED received per patient was 33.4 mSv (95% CI 29.3-37.5). A total of 49
      (20.8%) patients received an ED >= 50 mSv. The following factors were identified
      as independent predictors associated with an ED >= 50 mSv: Age older than 40
      years, need for surgery, age under 16 years at diagnosis and disease duration
      over 8 years. CONCLUSIONS: a substantial proportion of patients with Crohn's
      disease receive high doses of potentially carcinogenic ionizing radiation.
      Identification of the most susceptible patients to receive high doses of
      radiation, monitoring of effective doses received and the use of imaging
      techniques that do not require ionizing radiation (MR enterography, abdominal
      ultrasound) could contribute in reducing patients' exposure to potentially
      carcinogenic ionizing radiation.

PMID- 23130853
TI  - Endoscopic mucosal resection for proximal superficial lesions: efficacy and
      safety study in 59 consecutive resections.
AB  - INTRODUCTION: endoscopic mucosal resection is an accepted technique for the
      treatment of proximal gastrointestinal tract superficial lesions. OBJECTIVES: to
      evaluate the efficacy and safety of this procedure in the proximal
      gastrointestinal tract. MATERIAL AND METHODS: forty one consecutive patients (23
      males and 18 females, mean age of 61 +/- 11.5 years) were included in our study.
      Fifty nine resections were performed in these patients in 69 sessions. Lesions
      treated consisted of elevated lesions with high grade dysplasia in the context of
      Barrett's esophagus (group A), high grade dysplasia appearing in random biopsies
      taken during the follow-up of Barrett's esophagus (group B) and superficial
      gastroduodenal lesions (group C). Snare resection after submucosal injection,
      band ligator-assisted or cap-assisted mucosal resection were the chosen
      techniques. RESULTS: we resected 7 elevated lesions with high grade dysplasia in
      the context of Barrett's esophagus, 6 complete Barrett's esophagus with high
      grade dysplasia in 16 sequential sessions and 46 gastroduodenal superficial
      lesions (10 adenomas, 9 gastric superficial carcinomas, 18 carcinoid tumours and
      9 lesions of different histological nature). Resections in the two first groups
      were complete in 100% of the cases, and in 97.9% of the cases in group C.
      Complications included 2 cases of limited deferred bleeding (groups A and B) and
      another two cases of stenosis with little clinical relevance in Group B.
      CONCLUSIONS: a) endoscopic mucosal resection is an efficient technique for the
      treatment of proximal gastrointestinal tract superficial lesions; b) it is a safe
      procedure with a low percentage of complications, which can generally be managed
      endoscopically; and c) in contrast with other ablative techniques, endoscopic
      mucosal resection offers the possibility of a pathologic analysis of the samples.

PMID- 23130854
TI  - Efficacy of adalimumab for the treatment of extraintestinal manifestations of
      Crohn's disease.
AB  - BACKGROUND AND AIMS: Crohn's disease (CD) is commonly associated with
      inflammatory processes located in organs and systems others than the gut, which
      are known as extraintestinal manifestations (EIM) of the disease. The aim of this
      study was to assess the effectiveness of adalimumab (ADA) for the treatment of
      EIM in patients with CD. METHODS: forty two consecutive CD patients with at least
      one EIM were prospectively included in a open-label study. Patients received ADA
      (160 mg at week zero, 80 mg at week two and 40 mg every other week) over six
      months and the effectiveness and safety of ADA for EIMs were assessed. The
      influence of gender, age, smoking habits, family history of inflammatory bowel
      disease, phenotype and previous anti-TNF treatment on EIM resolution was also
      investigated. RESULTS: at month six, 76.2% of the patients showed remission or
      response in CD (33.3% remission and 42.9% any response). EIM showed a parallel
      course with CD in most cases, and showed remission or response in 66.7% of
      patients (38.1% remission and 28.5% any response). Patients with any response of
      their EIM condition were younger than those with no response (p = 0.04). No
      relationship was found between sex, tobacco, family history of IBD, phenotype and
      previous treatment with anti-TNF, and EIM resolution. CONCLUSIONS: adalimumab is
      effective in reducing EIM of CD. Age but not tobacco, CD phenotype and anti-TNF
      naive status appears to influence the response.

PMID- 23130855
TI  - Low co-existence rates of Lactobacillus spp. and Helicobacter pylori detected in
      gastric biopsies from patients with gastrointestinal symptoms.
AB  - BACKGROUND: bacterial diversity of the stomach includes various species. Among
      them, Helicobacter pylori, a microorganism which has been associated to gastric
      diseases, is frequently isolated in this habitat. In addition, Lactobacillus
      spp., a genus including probiotic strains, has also been documented in this
      habitat. The co-existence of these two species in the stomach of symptomatic
      patient needs to be elucidated. AIMS: our goal was to establish if Lactobacillus
      spp. and H. pylori co-exist in the stomach mucosa of symptomatic patients.
      METHODS: gastric biopsies (antrum and/or the body) from 427 Chilean patients with
      gastrointestinal discomfort were analyzed. The H. pylori infection and/or
      Lactobacillus spp. colonization status was determined for each patient by
      standard culture techniques, and statistical correlations between the presence of
      those species and the age, gender, or the severity of the gastric disease were
      also established. RESULTS: only 6.1% of the samples presented co-existence of
      Lactobacillus spp. and H. pylori. This former species was isolated in 42.6% of
      the patients as unique species, while Lactobacillus spp. was isolated as single
      species in 19.4% of the individuals. Chronic non-atrophic gastritis was prevalent
      in Lactobacillus spp. non colonized individuals, while chronic non-atrophic and
      chronic atrophic gastritis diagnosis was similar in Lactobacillus spp. harbouring
      individuals (p < 0.001). The presence of Lactobacillus spp. Significantly
      increased with age (p = 0.005), independently of gender. CONCLUSION: the negative
      Pearson correlation between Lactobacillus spp. and H. pylori (r = -0.112, p =
      0.020) indicates that the co-existence of both species is low in human gastric
      mucosa of symptomatic patients.

PMID- 23130856
TI  - Nutritional treatment in inflammatory bowel disease. An update.
AB  - BACKGROUND AND AIMS: enteral (EN) and parenteral (TPN) nutrition exert variable
      therapeutic effects on the induction and maintenance of remission in inflammatory
      bowel disease (IBD). This review aims to provide an updated discussion on the
      complex relationship between diet and IBD. METHODS: medline, Cochrane and Scopus
      database searches were conducted. Sources cited in the articles obtained were
      also searched to identify other potential sources of information. RESULTS:
      nutritional status is significantly compromised in IBD patients, especially those
      with Crohn's disease (CD). Apart from restoring malnourishment, dietary
      components contribute to modulate intestinal immune responses. Nutritional
      treatment is divided into support therapy and primary therapy to induce and
      maintain remission through TPN and EN. EN is considered a first-line therapy in
      children with active CD whereas it is usually used in adult CD patients when
      corticosteroid therapy is not possible. TPN has limited effects on IBD.En formula
      composition, in terms of carbohydrates, nitrogen source and bioactive molecules
      supplementation, differentially influence on IBD treatment outcomes. Other
      dietary components, such as poorly absorbed short-chain carbohydrate, polyols,
      and exogenous microparticles, also participate in the etiopathogenesis of IBD.
      Finally, new approaches to understanding the complex relationship between IBD and
      diet are provided by nutrigenenomic. CONCLUSION: further long-term, well-powered
      studies are required to accurately assess the usefulness of nutrition in treating
      IBD. In future research, the potential role of nutrient-gene interaction in drug
      trials and specific dietary formula compositions should be investigated in order
      to incorporate new knowledge about the etiopathology of IBD into nutritional
      intervention.

PMID- 23130857
TI  - Endoscopic closure of duodenal perforation with an over-the-scope clip during
      endoscopic ultrasound-guided cholangiopancreatography.

PMID- 23130858
TI  - Multiple lymphomatous polyposis of intestine as presentation of mantle cell
      lymphoma.

PMID- 23130859
TI  - Evaluation of the oncogenic risk of diffuse gastric polyposis. A case report.
AB  - Benign polyps of the stomach undergo malignant transformation at a rate
      correlating to the histological type and size of the proliferative lesion. We
      report a case of a 50-year-old Caucasian woman, affected by a diffuse gastric
      polyposis of both hyperplastic and adenomatous type. At endoscopy polyps were
      more than 1,000, scattered over the entire gastric cavity. The patient underwent
      total gastrectomy. The perilesional gastric mucosa was characterized by the
      presence of either atrophic or metaplastic areas and by a mild dysplasia. A
      single tubulo-villous adenomatous polyp was also present in the ascending tract
      of the colon. The absence of both high-grade dysplastic lesions and outbreaks of
      neoplastic transformation well correlated with the histochemical and molecular
      features, confirming the highly proliferative pattern of the polyps in the lack
      of signs of malignant progression.

PMID- 23130860
TI  - [Hemodynamic study of the liver].

PMID- 23130861
TI  - Pseudomembranous colitis and bacteremia in an immune competent patient associated
      with a rare specie of Clostridium (C. ramosum).

PMID- 23130862
TI  - Spontaneous hemoperitoneum due to rupture of short gastric artery after vomiting.

PMID- 23130863
TI  - Signet ring cell adenocarcinoma of the ampulla of Vater: a rare pathology.

PMID- 23130864
TI  - Therapeutic options in pancreatic pseudoaneurysms.

PMID- 23130865
TI  - Jejunal diverticular perforation due to gallstone ileus.

PMID- 23130866
TI  - Hepatocellular carcinoma in non-cirrhotic liver.

PMID- 23130867
TI  - Impulsivity trajectories and gambling in adolescence among urban male youth.
AB  - AIM: Building on the recent emerging literature on the impulsivity trajectory
      gambling association, this study investigated the association between
      developmental trajectories of teacher-rated impulsivity in early adolescence
      (ages 11-15 years) and subsequent gambling and gambling problems (i.e. at-risk
      and problem gambling) by age 19. DESIGN: Prospective cohort design. SETTING:
      Urban communities in Baltimore, Maryland. PARTICIPANTS: The sample consists of
      310 predominately minority (87%) and low socio-economic status (SES) (70%) males
      followed from first grade to late adolescence. MEASUREMENTS: Impulsivity was
      measured using teacher ratings of classroom behavior. Self-reported gambling
      behavior was assessed using the South Oaks Gambling Screen-Revised for
      Adolescents (SOGS-RA). FINDINGS: Results from a conventional growth model suggest
      that the intercept of the impulsivity development (as measured by the repeated
      assessments of impulsivity across the entire developmental period) was associated
      significantly with gambling. Results from a general growth mixture model
      evidenced two distinct trajectories: a high impulsivity trajectory (41% of the
      sample) and a low impulsivity trajectory (59% of the sample). Despite its non
      significant association with any gambling, heterogeneity in impulsivity
      development was associated significantly with gambling problems. Specifically,
      being in the high impulsivity trajectory doubled the odds of meeting criteria for
      at-risk or problem gambling [odds ratio (OR) = 2.09, 95% confidence interval
      (CI): 1.02, 4.27)] and tripled the odds of meeting criteria for problem gambling
      (OR = 2.84, 95% CI: 1.02, 7.91). CONCLUSIONS: Development in impulsivity is
      associated strongly with problem/at-risk gambling in adolescence among urban male
      youth. Findings highlight the importance of distinguishing gambling problems from
      any gambling when evaluating programs aimed at reducing youth gambling problems
      through reducing impulsivity.

PMID- 23130868
TI  - Renal malakoplakia presenting as a renal mass in a 55-year-old man: a case
      report.
AB  - INTRODUCTION: Malakoplakia is an uncommon chronic inflammatory condition that
      has a gross and microscopic appearance resembling that of xanthogranulomatous
      pyelonephritis. It is characterized by distinctive Michaelis-Gutmann bodies.
      Malakoplakia can affect any organ system but genitourinary tract involvement is
      the most common, particularly in immunocompromised individuals. Very rare cases
      have been reported to present as a unifocal lesion mimicking a renal tumor. CASE
      PRESENTATION: We report a case of renal malakoplakia in a 55-year-old Iranian man
      with a past history of recurrent urinary tract infections who presented with left
      flank pain. An ultrasound study showed a large solid left renal mass, and he
      underwent a left radical nephrectomy with a clinical diagnosis of a renal tumor.
      Pathology slides revealed the diffuse infiltration of sheets of Periodic Acid
      Schiff-positive histiocytes in his renal parenchyma; these cells showed strong
      immunoreactivity for CD 68. The final diagnosis was renal malakoplakia.
      CONCLUSION: Renal malakoplakia must be kept in mind for patients presenting with
      a renal mass and a history of long-term recurrent renal infections or renal
      failure. The large, rapidly growing nodules of malakoplakia may mimic renal cell
      carcinoma in imaging studies. In these cases, a true cut needle biopsy may help
      the correct diagnosis and prevent unnecessary surgery.

PMID- 23130869
TI  - Copper-catalyzed C-H azidation of anilines under mild conditions.
AB  - A novel and efficient copper-catalyzed azidation reaction of anilines via C-H
      activation has been developed. This method, in which the primary amine acts as a
      directing group by coordinating to the metal center, provides ortho azidation
      products regioselectively under mild conditions. This effective route for the
      synthesis of aryl azides is of great significance in view of the versatile
      reactivity of the azide products.

PMID- 23130870
TI  - Tetragonal and cubic zirconia multilayered ceramic constructs created by EPD.
AB  - The interest in electrophoretic deposition (EPD) for nanomaterials and ceramics
      production has widely increased due to the versatility of this technique to
      effectively combine different materials in unique shapes and structures. We
      successfully established an EPD layering process with submicrometer sized powders
      of Y-TZP with different mol percentages of yttrium oxide (3 and 8%) and produced
      multilayers of alternating tetragonal and cubic phases with a clearly defined
      interface. The rationale behind the design of these multilayer constructs was to
      optimize the properties of the final ceramic by combining the high mechanical
      toughness of the tetragonal phase of zirconia together with the high ionic
      conductivity of its cubic phase. In this work, a preliminary study of the
      mechanical properties of these constructs proved the good mechanical integrity of
      the multilayered constructs obtained as well as crack deflection in the interface
      between tetragonal and cubic zirconia layers.

PMID- 23130871
TI  - Unrecognised tuberculosis at antiretroviral therapy initiation is associated with
      lower CD4+ T cell recovery.
AB  - OBJECTIVES: To investigate whether an unrecognised diagnosis of tuberculosis (TB)
      at the start of antiretroviral therapy (ART) influences subsequent CD4+ T cell
      (CD4) count recovery in an urban HIV clinic in Uganda. METHODS: In a
      retrospective cohort study, a multivariable polynomial mixed effects model was
      used to estimate CD4 recovery in the first 96 weeks of ART in two groups of
      patients: prevalent TB (started ART while on TB treatment), unrecognised TB
      (developed TB within 6 months after start ART). RESULTS: Included were 511
      patients with a median baseline CD4 count of 57 cells/mm(3) (interquartile range:
      22-130), of whom 368 (72%) had prevalent TB and 143 (28%) had unrecognised TB.
      Compared with prevalent TB, unrecognised TB was associated with lower CD4 count
      recovery at 96 weeks: -22.3 cells/mm(3) (95% confidence interval -43.2 to -1.5, P
      = 0.036). These estimates were adjusted for gender, age, baseline CD4 count and
      the use of zidovudine-based regimen. CONCLUSIONS: Unrecognised TB at the time of
      ART initiation resulted in impaired CD4 recovery compared with TB treated before
      ART initiation. More vigilant screening with more sensitive and rapid TB
      diagnostics prior to ART initiation is needed to decrease the risk of ART
      associated TB and sub-optimal immune reconstitution.

PMID- 23130878
TI  - Increased registration of hypertension and cancer diagnoses after the
      introduction of a new reimbursement system.
AB  - OBJECTIVE: To investigate the impact on ICD coding behaviour of a new case-mix
      reimbursement system based on coded patient diagnoses. The main hypothesis was
      that after the introduction of the new system the coding of chronic diseases like
      hypertension and cancer would increase and the variance in propensity for coding
      would decrease on both physician and health care centre (HCC) levels. DESIGN:
      Cross-sectional multilevel logistic regression analyses were performed in periods
      covering the time before and after the introduction of the new reimbursement
      system. SETTING: Skaraborg primary care, Sweden. SUBJECTS: All patients (n = 76
      546 to 79 826) 50 years of age and older visiting 468 to 627 physicians at the 22
      public HCCs in five consecutive time periods of one year each. MAIN OUTCOME
      MEASURES: Registered codes for hypertension and cancer diseases in Skaraborg
      primary care database (SPCD). RESULTS: After the introduction of the new
      reimbursement system the adjusted prevalence of hypertension and cancer in SPCD
      increased from 17.4% to 32.2% and from 0.79% to 2.32%, respectively, probably
      partly due to an increased diagnosis coding of indirect patient contacts. The
      total variance in the propensity for coding declined simultaneously at the
      physician level for both diagnosis groups. CONCLUSIONS: Changes in the healthcare
      reimbursement system may directly influence the contents of a research database
      that retrieves data from clinical practice. This should be taken into account
      when using such a database for research purposes, and the data should be
      validated for each diagnosis.

PMID- 23130879
TI  - What is your diagnosis? Ventral neck mass in a cat.

PMID- 23130880
TI  - Mutation detection in Croatian patients with familial hypercholesterolemia.
AB  - Familial hypercholesterolemia (FH) is caused by mutations in the genes for LDLR,
      APOB or PCSK9, and identification of the causative mutation provides definitive
      diagnosis so that the patient can be treated, their relatives tested and,
      therefore, premature heart disease prevented. DNA of eight unrelated individuals
      with clinically diagnosed FH were analyzed using a High-Resolution Melting method
      (HRM) for the LDLR gene (coding region, promoter and intron/exon boundaries), the
      APOB gene (part exon 26) and the PCSK9 gene (exon7). Variations found were
      sequenced and the effect on function of confirmed variants examined using
      predictive algorithms. Gross deletions and insertions were analysed using MLPA.
      Three novel LDLR variants were found, p.(S470C), p.(C698R) and c.2312-2A>C. All
      were predicted to be pathogenic using predictive algorithms. Three previously
      reported disease-causing mutations were identified (p.(G20R), p.(N272T) and
      p.(S286R); the latter was also carried by a hypercholesterolaemic relative. One
      patient carried the pathogenic APOB variant p.(R3527Q). No large LDLR deletions
      nor insertions were found, neither were any PCSK9 variants identified. HRM is a
      sensitive method for screening for mutations. While the causative mutation has
      been identified in 88% of these clinically defined FH patients, there appears to
      be a high degree of allelic heterogeneity in Croatian patients.

PMID- 23130882
TI  - Potential use of hydrocarbons for aging Lucilia sericata blowfly larvae to
      establish the postmortem interval.
AB  - Previous studies on Diptera have shown the potential for the use of cuticular
      hydrocarbons' analysis in the determination of larval age and hence the
      postmortem interval (PMI) for an associated cadaver. In this work, hydrocarbon
      compounds, extracted daily until pupation from the cuticle of the blowfly Lucilia
      sericata (Diptera: Calliphoridae), have been analyzed using gas chromatography
      mass spectrometry (GC-MS). The results show distinguishing features within the
      hydrocarbon profile over the period of the larvae life cycle, with significant
      chemical changes occurring from the younger larvae to the postfeeding larvae.
      Further interpretation of the chromatograms using principal component analysis
      revealed a strong correlation between the magnitudes of particular principal
      components and time. This outcome suggests that, under the conditions of this
      study, the cuticular hydrocarbons evolve in a systematic fashion with time, thus
      supporting the potential for GC-MS analysis as a tool for establishing PMI where
      such a species is present. 

PMID- 23130883
TI  - Use of personalized ventilation for improving health, comfort, and performance at
      high room temperature and humidity.
AB  - The effect of personalized ventilation (PV) on people's health, comfort, and
      performance in a warm and humid environment (26 and 28 degrees C at 70% relative
      humidity) was studied and compared with their responses in a comfortable
      environment (23 degrees C and 40% relative humidity). Thirty subjects
      participated in five 4-h experiments in a climate chamber. Under the conditions
      with PV, the subjects were able to control the rate and direction of the supplied
      personalized flow of clean air. Subjective responses were collected through
      questionnaires. During all exposures, the subjects were occupied with tasks used
      to assess their performance. Objective measures of tear film stability,
      concentration of stress biomarkers in saliva, and eye blinking rate were taken.
      Using PV significantly improved the perceived air quality (PAQ) and thermal
      sensation and decreased the intensity of Sick Building Syndrome (SBS) symptoms to
      those prevailing in a comfortable room environment without PV. Self-estimated and
      objectively measured performance was improved. Increasing the temperature and
      relative humidity, but not the use of PV, significantly decreased tear film
      quality and the concentration of salivary alpha-amylase, indicating lower mental
      arousal and alertness. The use of PV improved tear film stability as compared to
      that in a warm environment without PV. PRACTICAL IMPLICATIONS: In practice, the
      supply of clean, cool, and less humid air by PV at each workstation will make it
      possible to raise room temperatures above the upper comfortable limit suggested
      in the present standards without adversely affecting the occupants' health [Sick
      Building Syndrome (SBS) symptoms], comfort (thermal and perceived air quality),
      and performance. This may lead to energy savings.

PMID- 23130881
TI  - DISC1 as a therapeutic target for mental illnesses.
AB  - INTRODUCTION: Many genetic studies have indicated that DISC1 is not merely
      "disrupted-in-schizophrenia," but is more generally implicated in various brain
      dysfunctions associated with aberrant neurodevelopment and intracellular
      signaling pathways. Thus, the DISC1 gene is mildly associated with a variety of
      brain disorders, including schizophrenia, mood disorders, and autism. This novel
      concept fits with the results from biological studies of DISC1, which include
      cell and animal models. AREAS COVERED: We review the molecular structure and
      functions of DISC1, particularly those in conjunction with its important
      interactors. Functions of these interacting proteins are also introduced under
      the concept of the "DISC1 interactome." Finally, we discuss how the DISC1
      interactome can provide potential therapeutic targets for mental illnesses.
      EXPERT OPINION: Modulation of DISC1 stability and post-transcriptional
      modifications may be key targets to address DISC1-related pathology. In addition,
      modulation of DISC1 interactors and the mechanisms of their interactions with
      DISC1 may also provide drug targets. Disc1 rodent models can subsequently be used
      as templates for in vivo validations of compounds designed for DISC1 and its
      interacting proteins. Furthermore, these rodents will serve as genetic models for
      schizophrenia and related conditions, especially in conjunction with their
      pathologies during the neurodevelopmental trajectory.

PMID- 23130884
TI  - Discovery of the novel HLA-DRB1*04:05:14 allele in a Taiwanese unrelated
      haematopoietic stem cell donor by a sequence-based typing method.
AB  - We report here a de novo HLA-DRB1*04 allele, DRB1*04:05:14, discovered in a
      Taiwanese unrelated volunteer bone marrow stem cell donor by a sequence-based
      typing method. In exon 2, the DNA sequence of DRB1*04:05:14 is identical to the
      sequence of DRB1*04:05:01 except the nucleotide at positions 321 where C is
      replaced by T (at codon 78; TAC->TAT). Due to the silent mutation, the nucleotide
      substitution produced no amino acid variation in comparison with DRB1*04:05:01.
      We assume DRB1*04:05:14 was derived from DRB1*04:05:01 via a point mutation. The
      probable HLA-A, -B and -DRB1 haplotype in association with DRB1*04:05:14 may be
      deduced as A*11-B*55-DRB1*04:05:14. We here report the Taiwanese ethnicity of
      DRB1*04:05:14. 

PMID- 23130885
TI  - Plasmonic-based sensing using an array of Au-metal oxide thin films.
AB  - An optical plasmonic-based sensing array has been developed and tested for the
      selective and sensitive detection of H(2), CO, and NO(2) at a temperature of 500 
      degrees C in an oxygen-containing background. The three-element sensing array
      used Au nanoparticles embedded in separate thin films of yttria-stabilized
      zirconia (YSZ), CeO(2), and TiO(2). A peak in the absorbance spectrum due to a
      localized surface plasmon resonance (LSPR) on the Au nanoparticles was monitored
      for each film during gas exposures and showed a blue shift in the peak positions
      for the reducing gases, H(2) and CO, and a red shift for the oxidizing gas,
      NO(2). A more in-depth look at the sensing response was performed using the
      multivariate methods of principal component analysis (PCA) and linear
      discriminant analysis (LDA) on data from across the entire absorbance spectrum
      range. Qualitative results from both methods showed good separation between the
      three analytes for both the full array and the Au-TiO(2) sample. Quantification
      of LDA cluster separation using the Mahalanobis distance showed better cluster
      separation for the array, but there were some instances with the lowest
      concentrations where the single Au-TiO(2) film had separation better than that of
      the array. A second method to quantify cluster separation in LDA space was
      developed using multidimensional volume analysis of the individual cluster
      volume, overlapped cluster volume, and empty volume between clusters. Compared to
      the individual sensing elements, the array showed less cluster overlap, smaller
      cluster volumes, and more space between clusters, all of which were expected for
      improved separability between the analytes.

PMID- 23130886
TI  - Same temporal niche, opposite rhythmicity: two closely related bioluminescent
      insects with opposite bioluminesce propensity rhythms.
AB  - Arachnocampa species, commonly called glowworms, are flies whose larvae use light
      to attract prey. Here we compare rhythmicity in two of the nine described
      species: the Tasmanian species, Arachnocampa tasmaniensis, which inhabits caves
      and wet forest, and the eastern Australian mainland species, A. flava, primarily
      found in subtropical rainforest. Both species show the same nocturnal glowing
      pattern in external (epigean) environments and the same inhibition of
      bioluminescence by light and both species show circadian regulation of
      bioluminescence. We find that the underlying circadian bioluminescence propensity
      rhythm (BPR) of the two species peaks at opposite phases of the day:night cycle.
      Larvae of A. flava, placed in constant darkness in the laboratory, bioluminesce
      during the subjective scotophase, typical of nocturnal animals, whereas A.
      tasmaniensis shows the opposite tendency, bioluminescing most intensely during
      the subjective photophase. In A. tasmaniensis, which are exposed to natural
      day:night cycles, light exposure during the day overrides the high
      bioluminescence propensity through negative masking and leads to a release of
      bioluminescence after dusk when the BPR is on the wane. A consequence is that A.
      tasmaniensis is able to start glowing at any phase of the light:dark cycle as
      soon as masking by light is released, whereas A. flava is locked into nocturnal
      bioluminescence. We suggest that the paradoxical BPR of A. tasmaniensis is an
      adaptation for living in the cave environment. Observations of bioluminescence in
      colonies of A. tasmaniensis located in the transition from a cave mouth to the
      dark zone show that glowing is inhibited by light exposure but a peak
      bioluminescence follows immediately after "dusk" at their location. The
      substantial difference in the circadian regulation of bioluminescence between the
      two species probably reflects adaptation to the cave (hypogean) habitat in A.
      tasmaniensis and the forest (epigean) habitat in A. flava.

PMID- 23130887
TI  - The ratio of parathyroid hormone to vitamin D is a determinant of cardiovascular
      risk and insulin sensitivity in adolescent girls.
AB  - BACKGROUND: Vitamin D insufficiency and higher testosterone are common in obese
      girls and may adversely affect glucose homeostasis and cardiovascular risk. Data
      are conflicting regarding the impact of parathyroid hormone (PTH) on these
      factors. Our objective was to determine associations of 25-hydroxyvitamin D (25
      OHD), PTH, and testosterone with measures of glucose homeostasis and
      cardiovascular risk in adolescent girls after controlling for regional adiposity,
      with the hypothesis that lower 25-OHD, a higher PTH or PTH/25-OHD ratio, and
      higher testosterone would be associated with lower insulin sensitivity and
      greater cardiovascular risk. METHODS: A total of 15 obese girls and 15 matched
      normal weight controls (12-18 years) underwent fasting measurements of 25-OHD,
      PTH, testosterone, sex hormone-binding globulin (SHBG), high-sensitivity C
      reactive protein (hsCRP), oral glucose tolerance testing, and quantification of
      visceral (VAT) and subcutaneous (SAT) fat by magnetic resonance imaging (MRI).
      RESULTS: There were no associations of 25-OHD with measures of glucose
      homeostasis or hsCRP. In contrast, PTH and PTH/25-OHD were associated negatively
      with homeostasis model assessment of insulin resistance (HOMA-IR) and positively
      with quantitative insulin sensitivity check index (QUICKI) in obese girls but not
      controls. These associations remained significant after controlling for body mass
      index standard deviation score (BMI-SDS), but not for VAT. On regression
      modeling, PTH/25-OHD was positively associated with hsCRP after controlling for
      BMI-SDS or VAT. Free testosterone positively predicted the corrected insulin
      response. CONCLUSIONS: In obese girls, PTH/25-OHD is positively associated with
      measures of insulin sensitivity and hsCRP. Further studies are needed to
      investigate the relationship between PTH and glucose homeostasis in obesity.

PMID- 23130888
TI  - Deep sequencing analysis of the transcriptomes of peanut aerial and subterranean
      young pods identifies candidate genes related to early embryo abortion.
AB  - The failure of peg penetration into the soil leads to seed abortion in peanut.
      Knowledge of genes involved in these processes is comparatively deficient. Here,
      we used RNA-seq to gain insights into transcriptomes of aerial and subterranean
      pods. More than 2 million transcript reads with an average length of 396 bp were
      generated from one aerial (AP) and two subterranean (SP1 and SP2) pod libraries
      using pyrosequencing technology. After assembly, sets of 49 632, 49 952 and 50
      494 from a total of 74 974 transcript assembly contigs (TACs) were identified in
      AP, SP1 and SP2, respectively. A clear linear relationship in the gene expression
      level was observed between these data sets. In brief, 2194 differentially
      expressed TACs with a 99.0% true-positive rate were identified, among which 859
      and 1068 TACs were up-regulated in aerial and subterranean pods, respectively.
      Functional analysis showed that putative function based on similarity with
      proteins catalogued in UniProt and gene ontology term classification could be
      determined for 59 342 (79.2%) and 42 955 (57.3%) TACs, respectively. A total of
      2968 TACs were mapped to 174 KEGG pathways, of which 168 were shared by aerial
      and subterranean transcriptomes. TACs involved in photosynthesis were
      significantly up-regulated and enriched in the aerial pod. In addition, two
      senescence-associated genes were identified as significantly up-regulated in the
      aerial pod, which potentially contribute to embryo abortion in aerial pods, and
      in turn, to cessation of swelling. The data set generated in this study provides
      evidence for some functional genes as robust candidates underlying aerial and
      subterranean pod development and contributes to an elucidation of the
      evolutionary implications resulting from fruit development under light and dark
      conditions.

PMID- 23130889
TI  - Risk factors for nasal malignancies in German men: the South-German Nasal cancer
      study.
AB  - BACKGROUND: There are few studies of the effects of nasal snuff and environmental
      factors on the risk of nasal cancer. This study aimed to investigate the impact
      of using nasal snuff and of other risk factors on the risk of nasal cancer in
      German men. METHODS: A population-based case-control study was conducted in the
      German Federal States of Bavaria and Baden-Wurttemberg. Tumor registries and ear,
      nose and throat departments provided access to patients born in 1926 or later.
      RESULTS: Telephone interviews were conducted with 427 cases (mean age 62.1 years)
      and 2.401 population-based controls (mean age 60.8 years). Ever-use of nasal
      snuff was associated with an odds ratio (OR) for nasal cancer of 1.45 (95%
      confidence interval [CI] 0.88-2.38) in the total study population, whereas OR in
      smokers was 2.01 (95% CI 1.00-4.02) and in never smokers was 1.10 (95% CI 0.43
      2.80). The OR in ever-smokers vs. never-smokers was 1.60 (95% CI 1.24-2.07), with
      an OR of 1.06 (95% CI 1.05-1.07) per pack-year smoked, and the risk was
      significantly decreased after quitting smoking. Exposure to hardwood dust for at
      least 1 year resulted in an OR of 2.33 (95% CI 1.40-3.91) in the total
      population, which was further increased in never-smokers (OR 4.89, 95% CI 1.92
      12.49) in analyses stratified by smoking status. The OR for nasal cancer after
      exposure to organic solvents for at least 1 year was 1.53 (1.17-2.01). Ever-use
      of nasal sprays/nasal lavage for at least 1 month rendered an OR of 1.59 (1.04
      2.44). The OR after use of insecticides in homes was 1.48 (95% CI 1.04-2.11).
      CONCLUSIONS: Smoking and exposure to hardwood dust were confirmed as risk factors
      for nasal carcinoma. There is evidence that exposure to organic solvents, and in
      house use of insecticides could represent novel risk factors. Exposure to
      asbestos and use of nasal snuff were risk factors in smokers only.

PMID- 23130890
TI  - Acute termination of human atrial fibrillation by identification and catheter
      ablation of localized rotors and sources: first multicenter experience of focal
      impulse and rotor modulation (FIRM) ablation.
AB  - INTRODUCTION: Catheter ablation of atrial fibrillation (AF) currently relies on
      eliminating triggers, and no reliable method exists to map the arrhythmia itself
      to identify ablation targets. The aim of this multicenter study was to define the
      use of Focal Impulse and Rotor Modulation (FIRM) for identifying ablation
      targets. METHODS: We prospectively enrolled the first (n = 14, 11 males)
      consecutive patients undergoing FIRM-guided ablation for persistent (n = 11) and
      paroxysmal AF at 5 centers. A 64-pole basket catheter was used for panoramic
      right and left atrial mapping during AF. AF electrograms were analyzed using a
      novel system to identify sustained rotors (spiral waves), or focal beats
      (centrifugal activation to surrounding atrium). Ablation was performed first at
      identified sources. The primary endpoints were acute AF termination or
      organization (>10% cycle length prolongation). Conventional ablation was
      performed only after FIRM-guided ablation. RESULTS: Twelve out of 14 cases were
      mapped. AF sources were demonstrated in all patients (average of 1.9 +/- 0.8 per
      patient). Sources were left atrial in 18 cases, and right atrial in 5 cases, and
      21/23 were rotors. FIRM-guided ablation achieved the acute endpoint in all
      patients, consisting of AF termination in n = 8 (4.9 +/- 3.9 minutes at the
      primary source), and organization in n = 4. Total FIRM time for all patients was
      12.3 +/- 8.6 minutes. CONCLUSIONS: FIRM-guided ablation revealed localized AF
      rotors/focal sources in patients with paroxysmal, persistent and longstanding
      persistent AF. Brief targeted FIRM-guided ablation at a priori identified sites
      terminated or substantially organized AF in all cases prior to any other
      ablation.

PMID- 23130891
TI  - Percutaneous transhepatic access for ablation of atypical atrial flutter in
      complex congenital heart disease.

PMID- 23130892
TI  - Ultrahigh torsional stiffness and strength of boron nitride nanotubes.
AB  - We report the experimental and theoretical study of boron nitride nanotube (BNNT)
      torsional mechanics. We show that BNNTs exhibit a much stronger mechanical
      interlayer coupling than carbon nanotubes (CNTs). This feature makes BNNTs up to
      1 order of magnitude stiffer and stronger than CNTs. We attribute this interlayer
      locking to the faceted nature of BNNTs, arising from the polarity of the B-N
      bond. This property makes BNNTs superior candidates to replace CNTs in
      nanoelectromechanical systems (NEMS), fibers, and nanocomposites.

PMID- 23130893
TI  - The impact of lifestyle-related risk factors on cardiac response to ischemia and
      possibilities to restore impaired ischemic tolerance.
AB  - Risk factors (RF) of cardiovascular diseases associated with modern lifestyle,
      such as stress, chronically increased blood pressure, hyperglycemia and
      dyslipidemia have a negative impact on the heart exposed to ischemia: they may
      facilitate its lethal injury (myocardial infarction) and occurrence of sudden
      death due to ventricular arrhythmias. On the other hand, some stressful stimuli
      related to RF including reactive oxygen species, transient episodes of ischemia
      (hypoxia), high glucose and other may play a dual role in the pathogenesis of
      ischemia/reperfusion (I/R) injury (IRI). Besides their deleterious effects, these
      factors may trigger adaptive processes in the heart resulting in greater
      resistance against IRI, which is also a characteristic feature of the female
      myocardium. However, sensitivity to ischemia is increasing with age in both
      genders. Current research indicates that comorbidity related to lifestyle may
      impair the cardiac response to acute ischemia not only by interference with
      pathophysiological mechanisms of IRI per se, but via suppression of intrinsic
      protective mechanisms in the heart and its ability to tolerate the ischemic
      challenges, although the role of RF has not been unequivocally proven. Moreover,
      even pathologically altered myocardium need not completely lose its adaptive
      potential. In addition, increased ischemic tolerance can be induced by the
      pleiotropic (independent of the primary) effects of some hypolipidemic and
      antidiabetic drugs, even in the diseased myocardium. This review addresses the
      issue of the impact of RF on cellular cardioprotective mechanisms and the
      possibilities to restore adaptive potential in subjects challenged with several
      RF. Reactivation of adaptive processes in the myocardium taking into
      consideration gender and age can contribute to optimalization of antiischemic
      therapy.

PMID- 23130894
TI  - Purified acetaminophen-glutathione conjugate is able to induce oxidative stress
      in rat liver mitochondria.
AB  - Acetaminophen overdose is the most often cause of acute liver injury. The toxic
      mechanism is linked to formation of an active metabolite that reacts with
      glutathione generating acetaminophen-glutathione conjugate (APAP-SG). This
      compound has been recognized to be non-toxic generally. Our preliminary results
      showed, however, that APAP-SG could possess a toxic effect too. Therefore, the
      aim of our study was to prepare, purify and to test possible toxicity of APAP-SG.
      We prepared APAP-SG using organic synthesis. The conjugate was purified by
      preparative HPLC and its structure was confirmed using mass spectrometry. Final
      purity of APAP-SG was >98 %. We estimated a toxic effect of APAP-SG in isolated
      rat liver mitochondria using a fluorescent ROS probe. We assessed ROS production
      in presence of complex I or complex II substrates. The increase of ROS-dependent
      fluorescence in presence of glutamate/malate was 104 +/- 13 % and 130 +/- 10 % in
      1 mM and 5 mM APAP-SG, respectively, in comparison with controls. ROS production
      related to presence of complex II substrate was enhanced 4-times in APAP-SG (5
      mM) treated mitochondria (compared to controls). We conclude, we proved our
      hypothesis that APAP-SG conjugate is able to induce a mitochondrial impairment
      leading to enhanced ROS production.

PMID- 23130895
TI  - Involvement of membrane fluidity in endogenous protective processes running on
      subcellular membrane systems of the rat heart.
AB  - Membrane fluidity is a widely recognized biophysical variable that provides
      information about structural organization of the subcellular membranes exhibiting
      physical characteristics of liquid crystals. The term "fluidity" reflects in this
      case the tightness in packing of acyl parts of the membrane phospholipid
      molecules, a feature that may influence considerably the molecular mobility and
      via that also the sensitivity and reactivity of membrane-bound transporters,
      receptors and enzyme systems. Data presented in this review are aimed to
      demonstrate the substantial role of changes in membrane fluidity occurring in the
      processes associated with endogenous protection observed in cardiac sarcolemma
      and mitochondria in diverse pathologies, particularly in diabetes and
      hypertension.

PMID- 23130896
TI  - Influence of allopurinol on evoked cortical afterdischarges during early
      ontogenesis.
AB  - The aim of our study was to test the hypothesis, whether repeated allopurinol pre
      treatment (in dose of 135 mg/kg s.c.) can influence changes of brain excitability
      caused by long-term hypoxia exposition in young immature rats. Rat pups were
      exposed together with their mother in to an intermittent hypobaric hypoxia
      (simulated altitude of 7 000 m) since the day of birth till the 11th day
      (youngest experimental group) or 17th day for 8 hours a day. Allopurinol was
      administered daily immediately before each hypoxia exposition. The duration of
      evoked afterdischarges (ADs) and the shape of evoked graphoelements were
      evaluated in 12, 18, 25 and 35-day-old freely moving male pups. Hypobaric hypoxia
      prolonged the duration of ADs in 12, 18 and 25-day-old rats. The ADs were
      prolonged in 35-day-old rats only after the first stimulation. Allopurinol
      shorted the duration of ADs only in 12-day-old pups. In older experimental group
      the effect of allopurinol treatment was less pronounced.

PMID- 23130897
TI  - Gender impact on electrophysiological activity of the brain.
AB  - Gender is presumed to be one of the factors causing interindividual variability
      in the brain's electrophysiological parameters. Our aim was to characterize the
      role of gender in visual evoked potentials (VEPs), event-related potentials
      (ERPs), visual mismatch negativity (vMMN) and the spectral characteristics of the
      EEG. We examined 42 healthy volunteers (21 women and 21 men, aged 20-29 years).
      We measured VEPs in response to pattern-reversal and motion-onset stimulation,
      ERPs in an oddball paradigm and vMMN in response to a combination of motion
      directions presented in the visual periphery. P100 peak latency for 40' reversal
      VEPs was significantly shorter in women than in men as determined using a non
      parametric Wilcoxon signed-rank test. In addition, women showed higher relative
      EEG spectral power in the alpha band (p=0.023) and lower power in the theta band
      (p=0.004). Our results in this small but homogeneous group of subjects confirm
      previously reported gender influences on pattern-reversal VEPs and the EEG
      frequency spectrum. Gender should be taken into consideration in establishing
      norms on these measures. We found no statistically significant differences
      between women and men for any of the other stimuli presented.

PMID- 23130898
TI  - Do prenatally methamphetamine-exposed adult male rats display general
      predisposition to drug abuse in the conditioned place preference test?
AB  - Drug abuse of pregnant women is a growing problem. The effect of prenatal drug
      exposure may have devastating effect on development of the offsprings that may be
      long-term or even permanent. One of the most common drug abused by pregnant women
      is methamphetamine (MA), which is also the most frequently abused illicit drug in
      the Czech Republic. Our previous studies demonstrated that prenatal MA exposure
      alters behavior, cognition, pain and seizures in adult rats in sex-specific
      manner. Our most recent studies demonstrate that prenatal MA exposure makes adult
      rats more sensitive to acute injection of the same or related drugs than their
      controls. The aim of the present study was to examine the effect of prenatal MA
      exposure on drug-seeking behavior of adult male rats tested in the Conditioned
      place preference (CPP). Adult male rats were divided to: prenatally MA-exposed (5
      mg/kg daily for the entire prenatal period), prenatally saline-exposed (1 ml/kg
      of physiological saline) and controls (without maternal injections). The
      following drugs were used in the CPP test in adulthood: MA (5 mg/kg), amphetamine
      (5 mg/kg), cocaine (5 and 10 mg/kg), morphine (5 mg/kg), MDMA (5 mg/kg) and THC
      (2 mg/kg). Our data demonstrated that prenatally MA-exposed rats displayed higher
      amphetamine-seeking behavior than both controls. MA as well as morphine induced
      drug-seeking behavior of adult male rats, however this effect did not differ
      based on the prenatal MA exposure. In contrast, prenatal MA exposure induced
      rather tolerance to cocaine than sensitization after the conditioning in the CPP.
      MDMA and THC did not induce significant effects. Even though the present data did
      not fully confirmed our hypotheses, future studies are planned to test the drug
      seeking behavior also in self-administration test.

PMID- 23130899
TI  - Behavioral and antinociceptive effects of different psychostimulant drugs in
      prenatally methamphetamine-exposed rats.
AB  - Prenatal exposure to methamphetamine (METH) increases nociceptive sensitivity in
      adult rats. As the strong analgesics have high abuse potential and drugs of abuse
      are known to have analgesic properties, the aim was to study analgesic effect of
      different psychostimulants in control and prenatally METH-exposed rats. Latencies
      of withdrawal reflexes of hind limbs and the tail on thermal nociceptive stimuli
      were repeatedly measured in 15-min intervals after the application of 5 mg/kg
      s.c. of amphetamine (AMPH), methamphetamine (METH), cocaine (COC), 3,4
      methylenedioxymethamphetamine (MDMA) or morphine (MOR). In all groups, AMPH
      induced on hind limbs stronger analgesia than METH and MDMA whereas COC and MOR
      were practically without any effect. On the tail, effect of AMPH did not differ
      from that of MOR. All psychostimulants increased defecation in comparison with
      MOR and in all groups the number of defecation boluses positively correlated with
      analgesia of the hind limbs. We did not confirm that prenatal exposure to METH
      makes adult rats more sensitive either to same drug or to other psychostimulants.
      The different analgesic potencies of psychostimulants and MOR at different body
      sites indicate the possible existence of a somatotopic organization of pain
      inhibition, which is controlled by different mechanisms.

PMID- 23130900
TI  - Neurostimulation methods in the treatment of chronic pain.
AB  - The main neuromodulatory methods using neurostimulation principles are described.
      It concerns peripheral nerve stimulation (PNS), spinal cord stimulation (SCS),
      deep brain stimulation (DBS), motor cortex stimulation (MSC), and repetitive
      transcranial magnetic stimulation (rTMS). For each method the history,
      pathophysiology, the principles for use and the associated diagnoses are
      mentioned. Special attention is focused on the most common neuromodulatory
      invasive methods like SCS and MCS and non-invasive methods such as rTMS. In
      addition to the positive effects, side effects and complications are described
      and discussed in detail. In conclusion, neuromodulatory (neurostimulatory)
      techniques are highly recommended for the treatment of different types of
      pharmacoresistant pain.

PMID- 23130901
TI  - Pleiotropic effects of simvastatin are associated with mitigation of apoptotic
      component of cell death upon lethal myocardial reperfusion-induced injury.
AB  - Although statins exert non-lipid cardioprotective effects, their influence on
      cell death is not fully elucidated. For this purpose, we investigated whether
      simvastatin treatment (S, 10 mg/kg, 5 days) is capable of mitigating
      ischemia/reperfusion-induced (IR) apoptosis in the isolated rat hearts, which was
      examined using immunoblotting analysis. In addition, the content of signal
      transducer and activator of transcription 3 (STAT3) and its active form,
      phosphorylated STAT3 (pSTAT3-Thr(705)), was analyzed. Simvastatin induced neither
      variations in the plasma lipid levels nor alterations in the baseline content of
      analysed proteins with the exception of upregulation of cytochrome C.
      Furthermore, simvastatin significantly increased the baseline levels of pSTAT3 in
      contrast to the control group. In the IR hearts, simvastatin reduced the
      expression of Bax and non-cleaved caspase-3. In these hearts, phosphorylation of
      STAT3 did not differ in comparison to the non-treated IR group, however total
      STAT3 content was slightly increased. The improved recovery of left ventricular
      developed pressure co-existed with the increased Bcl-2/Bax ratio. In conclusion,
      pleiotropic action of statins may ameliorate viability of cardiomyocytes by
      favouring the expression of anti-apoptotic Bcl-2 and downregulating the pro
      apoptotic markers; however STAT3 does not seem to be a dominant regulator of this
      anti-apoptotic action of simvastatin.

PMID- 23130902
TI  - Rho-kinase inhibition attenuates acute hypoxic fetoplacental vasoconstriction in
      the rat.
AB  - The vessels on the fetal side of the placenta differ from most other vascular
      beds except the lungs in that they respond to acute hypoxia by vasoconstriction.
      An essential role of calcium influx in the mechanism of this hypoxic
      fetoplacental vasoconstriction (HFPV) has been shown previously. That finding
      does not, however, exclude the possible involvement of other mechanisms of
      vascular tone regulation. In this study we tested the hypothesis that Rho-kinase
      mediated calcium sensitization is involved in HFPV. We used a model of isolated
      rat placenta dually perfused (from both the maternal and fetal side) with Krebs
      salt solution saturated with normoxic and hypoxic gas mixture respectively at
      constant flow rate. Rho-kinase pathway was inhibited by fasudil (10 microM). We
      found that fasudil reduced basal normoxic fetoplacental vascular resistance and
      completely prevented HFPV. This suggests that the activity of Rho-kinase
      signaling pathway is essential for HFPV.

PMID- 23130903
TI  - QT dispersion and electrocardiographic changes in women with gestational diabetes
      mellitus.
AB  - Gestational diabetes mellitus (GDM) represents additional risks to both mother
      and infant. Moreover it increases a woman's risk of cardiovascular disease in the
      postpartum. The aim of our study was therefore to detect changes of both the QT
      dispersion and the electrical heart field that could be typical for GDM. Body
      surface potential maps were obtained using the Cardiac 112.2 device from 26 young
      women with GDM and 54 young healthy pregnant women in the 36th week of pregnancy.
      The same recordings were obtained from 18 healthy women in the same age (19-36
      years). The average QT dispersion (+/-SD) in women suffering from GDM was
      significantly higher (107 +/- 25 ms) both than in those with physiological
      pregnancy (73 +/- 18 ms) and than in the normal subjects (34 +/- 12 ms)
      (P<0.001). Moreover we have found in GDM patients shorter QRS complex 82.0 +/-
      6.8 ms vs. 89.5 +/- 8.2 ms in healthy pregnant women and 90.8 +/- 7.9 ms in the
      control group (p=0.011), more horizontal electrical heart axis [16.4 +/- 20.1
      degrees  vs. 42.4 +/- 28.7 degrees  and 74.6 +/- 39.2 degrees  respectively
      (P<0.05)] and lower some depolarization and repolarization amplitudes on
      isopotential and isointegral maps. According to these results we suppose that
      described electrocardiographic changes reflect a deterioration of the complete
      process of ventricular depolarization and repolarization in GDM.

PMID- 23130904
TI  - Hemodynamic and metabolic parameters during prolonged cardiac arrest and
      reperfusion by extracorporeal circulation.
AB  - Extracorporeal membranous oxygenation (ECMO) is increasingly used in the
      management of refractory cardiac arrest. Our aim was to investigate early effects
      of ECMO after prolonged cardiac arrest. In fully anesthetized swine (48 kg, N=18)
      ventricular fibrillation (VF) was induced and untreated period (20 min) of
      cardiac arrest commenced, followed by 60 min extracorporeal reperfusion (ECMO
      flow 100 ml/kg.min). Hemodynamics, arterial blood gasses, plasma potassium,
      tissue oximetry (StO(2)) and cardiac (EGM) and cerebral (BIS)
      electrophysiological parameters were continuously recorded and analyzed. Within 3
      minutes of VF hemodynamic and oximetry parameters fall abruptly while metabolic
      parameters destabilize gradually over 20 minutes peaking at pH 7.04 +/- 0.05,
      pCO(2) 89 +/- 14 mmHg, K(+) 8.5 +/- 1.6 mmol/l. During reperfusion most
      parameters restore rapidly: within 3-5 minutes mean arterial pressure reaches >40
      mmHg, StO(2)>50 %, paO(2)>100 mmHg, pCO(2)<50 mmHg, K(+)<5 mmol/l. EGMs mean
      amplitude peaks at 4.5 +/- 2.4 min. Cerebral activity (BIS>60) reappeared in 5
      animals after 87 +/- 21 min. In 12/18 animals return of spontaneous circulation
      was achieved. In conclusions, ECMO provides rapid restitution of internal milieu
      even after prolonged arrest. However, despite normalization of global parameters
      full recovery was not guaranteed since cardiac and cerebral electrical activities
      were sufficiently restored only in some animals. More sensitive and organ
      specific indicators need to be identified in order to estimate adequacy of
      cardiac support devices.

PMID- 23130905
TI  - Effect of short- and long-term high-fat feeding on autophagy flux and lysosomal
      activity in rat liver.
AB  - Autophagy-lysosomal pathway is a cellular mechanism ensuring degradation of
      various macromolecules like proteins or triacylglycerols (TAG). Its disruption is
      related to many pathological states, including liver steatosis. We compared the
      effect of short- and long-established steatosis on the intensity of autophagy
      lysosomal pathway in rat liver. The experiments were carried out on 3-month old
      Wistar rats fed standard (SD) or high-fat diet for 2 (HF-2) or 10 (HF-10) weeks.
      HF diet administered animals accumulated an increased amount of TAG in the liver
      (HF-2->HF-10). Autophagy flux was up-regulated in HF-2 group but nearly inhibited
      after 10 weeks of HF administration. The expression of autophagy related genes
      was up-regulated in HF-2 but normal in HF-10. In contrast, total activities of
      two lysosomal enzymes, lysosomal lipase (LAL) and acid phosphatase, were
      unaffected in HF-2 but significantly increased in HF-10 groups. mRNA expression
      of lysosomal enzymes was not affected by the diet. We conclude that in a state of
      metabolic unbalance (steatosis), autophagy machinery and lysosomal enzymes
      expression are regulated independently. The accumulation of TAG in the liver is
      associated with the increase of total LAL activity and protein expression. In
      contrast, the autophagy response is bi-phasic and after rapid increase it is
      significantly diminished. This may represent an adaptive mechanism that
      counteracts the excessive degradation of substrate, i.e. TAG, and eliminate over
      production of potentially hazardous lipid-degradation intermediates.

PMID- 23130906
TI  - Transcriptome temporal and functional analysis of liver regeneration termination.
AB  - Decades of liver regeneration studies still left the termination phase least
      elucidated. However regeneration ending mechanisms are clinicaly relevant. We
      aimed to analyse the timing and transcriptional control of the latest phase of
      liver regeneration, both controversial. Male Wistar rats were subjected to 2/3
      partial hepatectomy with recovery lasting from 1 to 14 days. Time-series
      microarray data were assessed by innovative combination of hierarchical
      clustering and principal component analysis and validated by real-time RT-PCR.
      Hierarchical clustering and principal component analysis in agreement
      distinguished three temporal phases of liver regeneration. We found 359 genes
      specifically altered during late phase regeneration. Gene enrichment analysis and
      manual review of microarray data suggested five pathways worth further study:
      PPAR signalling pathway; lipid metabolism; complement, coagulation and
      fibrinolytic cascades; ECM remodelling and xenobiotic biotransformation.
      Microarray findings pertinent for termination phase were substantiated by real
      time RT-PCR. In conclusion, transcriptional profiling mapped late phase of liver
      regeneration beyond 5(th) day of recovery and revealed 5 pathways specifically
      acting at this time. Inclusion of longer post-surgery intervals brought improved
      coverage of regeneration time dynamics and is advisable for further works.
      Investigation into the workings of suggested pathways might prove helpful in
      preventing and managing liver tumours.

PMID- 23130907
TI  - Steatotic rat hepatocytes in primary culture are more susceptible to the acute
      toxic effect of acetaminophen.
AB  - Acetaminophen (APAP) overdose is the most common cause of acute liver failure in
      humans. Non-alcoholic fatty liver disease is the most frequent chronic liver
      disease in developed countries. The aim of our work was to compare the effect of
      APAP on intact rat hepatocytes and hepatocytes isolated from steatotic liver in
      primary cultures. Male Wistar rats were fed with standard diet (10 % energy from
      fat) and high-fat diet (71 % energy from fat) for 6 weeks and then hepatocytes
      were isolated. After cell attachment, APAP (1; 2.5; 3.75 and 5 mM) was added to
      culture media (William's E medium) and hepatocytes were cultured for up to 24
      hours. APAP caused more severe dose-dependent damage of steatotic hepatocytes as
      documented by increased release of lactate dehydrogenase (LDH) and LDH leakage,
      decreased activity of cellular dehydrogenases (WST-1 test) and reduced albumin
      production. Intact steatotic hepatocytes contained lower amount of reduced
      glutathione (GSH). Treatment with APAP (1 and 2.5 mmol/l) caused more pronounced
      decrease in GSH in steatotic hepatocytes. ROS (reactive oxygen species) formation
      after 24-hour incubation was significantly higher in fatty hepatocytes using APAP
      at concentration of 3.75 and 5 mmol/l. Interleukin 6 (IL-6) production was
      elevated in 2.5 mM APAP-treated nonsteatotic and steatotic hepatocyte cultures at
      8 hours, compared to appropriate controls. In conclusions, our results indicate
      that steatotic hepatocytes exert higher sensitivity to the toxic action of APAP.
      This sensitivity may be caused by lower content of GSH in intact steatotic
      hepatocytes and by more pronounced APAP-induced decrease in intracellular
      concentration of GSH.

PMID- 23130908
TI  - Enhanced nanoscale resistive switching memory characteristics and switching
      mechanism using high-Ge-content Ge0.5Se0.5 solid electrolyte.
AB  - We demonstrate enhanced repeatable nanoscale bipolar resistive switching memory
      characteristics in Al/Cu/Ge0.5Se0.5/W, as compared with Al/Cu/Ge0.2Se0.8/W
      structures, including stable AC endurance (>105 cycles), larger average SET
      voltage (approximately 0.6 V), excellent data retention (>105 s) at 85 degrees C,
      and a high resistance ratio (>104) with a current compliance of 8 MUA and a small
      operation voltage of +/-1.5 V. A small device size of 150 * 150 nm2 and a Cu
      nanofilament with a small diameter of 30 nm are both observed by high-resolution
      transmission electron microscope in the SET state. The GexSe1 - x solid
      electrolyte compositions are confirmed by both energy-dispersive X-ray
      spectroscopy and X-ray photoelectron spectroscopy. The switching mechanism relies
      on the smaller barrier heights for holes rather than for electrons; the
      positively charged Cuz+ ions (i.e., holes) migrate through the defects in the
      GexSe1 - x solid electrolytes during SET/RESET operations. Hence, the Cu
      nanofilament starts to grow at the Ge0.5Se0.5/W interface, and starts to dissolve
      at the Cu/Ge0.5Se0.5 interface, as illustrated in the energy band diagrams. Owing
      to both the higher barrier for hole injection at the Cu/Ge0.5Se0.5 interface than
      at the Cu/Ge0.2Se0.8 interface and greater thermal stability, the resistive
      switching memory characteristics of the Al/Cu/Ge0.5Se0.5/W are improved relative
      to the Al/Cu/Ge0.2Se0.8/W devices. The Al/Cu/Ge0.5Se0.5/W memory device can also
      be operated with a low current compliance of 1 nA, and hence, a low SET/RESET
      power of 0.61 nW/6.4 pW is achieved. In addition, a large memory size of 1,300
      Pbit/in2 is achieved with a small nanofilament diameter of  0.25 A for a small
      current compliance of 1 nA.

PMID- 23130909
TI  - Intravenous iron sucrose versus oral iron ferrous sulfate for antenatal and
      postpartum iron deficiency anemia: a randomized trial.
AB  - OBJECTIVE: To compare oral iron to intravenous iron administration to women in
      late pregnancy and/or after labor to correct iron deficiency. METHODS: 271 anemic
      women (148 pregnant women and 123 women post lower segment caesarean section)
      with hemoglobin (Hb) levels below 110 g/L were enrolled over a two-year period
      and randomized to receive either two tablets FGF (ferrous sulfate with folic
      acid) or 400 mg of intravenous iron sucrose plus folic acid 600 ug. Treatment
      effectiveness was assessed by measuring Hb and ferritin postpartum on day 1, day
      14 and day 42. Transfusions of red blood cells and adverse drug reactions were
      recorded. RESULTS: Data of 214 women were available for analysis. Both forms of
      iron replacement therapy led to increased hemoglobin and ferritin levels over the
      testing period. Ferritin was significantly higher in the i.v. iron treatment
      group compared to the oral iron treatment group (p = 0.004) two weeks after
      delivery, while Hb values did not differ between the groups. No serious adverse
      drug reactions were observed. Red blood cell transfusion rate was low (1.9%),
      with equal rates observed in both treatment groups. CONCLUSION: Intravenous and
      oral irons were both effective in correcting peripartum anemia, although
      intravenous iron restored stores faster than oral iron.

PMID- 23130910
TI  - Quetiapine-induced sleep-related eating disorder-like behavior: a case series.
AB  - INTRODUCTION: Somnambulism or sleepwalking is a disorder of arousal from non
      rapid eye movement sleep. The prevalence of sleep-related eating disorder has
      been found to be approximately between 1% and 5% among adults. Many cases of
      medication-related somnambulism and sleep-related eating disorder-like behavior
      have been reported in the literature. Quetiapine, an atypical antipsychotic
      medication, has been associated with somnambulism but has not yet been reported
      to be associated with sleep-related eating disorder. CASE PRESENTATION: Case 1 is
      a 51-year-old obese African American male veteran with a body mass index of
      34.11kg/m2 and severe sleep apnea who has taken 150mg of quetiapine at bedtime
      for more than one year for depression. He developed sleepwalking three to four
      nights per week which resolved after stopping quetiapine while being compliant
      with bi-level positive pressure ventilation therapy. At one year follow-up, his
      body mass index was 32.57kg/m2.Case 2 is a 50-year-old African American female
      veteran with a body mass index of 30.5kg/m2 and mild sleep apnea who has taken
      200mg of quetiapine daily for more than one year for depression. She was
      witnessed to sleepwalk three nights per week which resolved after discontinuing
      quetiapine while being treated with continuous positive airway pressure. At three
      months follow-up, her body mass index was 29.1kg/m2. CONCLUSION: These cases
      illustrate that quetiapine may precipitate complex motor behavior including sleep
      related eating disorder and somnambulism in susceptible patients. Atypical
      antipsychotics are commonly used in psychiatric and primary care practice, which
      means the population at risk of developing parasomnia may often go unrecognized.
      It is important to recognize this potential adverse effect of quetiapine and, to
      prevent injury and worsening obesity, discuss this with the patients who are
      prescribed these medications.

PMID- 23130912
TI  - Misclassification of pregnancy-related deaths in adult mortality surveys: case
      study in Senegal.
AB  - OBJECTIVE: In countries with limited vital registration data, maternal mortality
      levels are often estimated using siblings' survival histories (SSH) collected
      during retrospective adult mortality surveys. We explored how accurately adult
      deaths can be classified as pregnancy related using such data. METHOD: The study
      was conducted in a rural area of south-eastern Senegal with high maternal
      mortality, Bandafassi. We used data from a demographic surveillance system (DSS)
      in this area to identify deaths of women at reproductive ages between 2003 and
      2009 and to locate the surviving adult sisters of the deceased and interview
      them. Siblings' survival histories were linked at the individual level to death
      records, and verbal autopsy data obtained by the demographic surveillance system.
      We compared the classification of adult female deaths as pregnancy related or not
      in interviews and DSS records. RESULTS: There were 91 deaths at reproductive ages
      in the Bandafassi DSS between 2003 and 2009, but only 59 had known surviving
      sisters. Some deaths were omitted by respondents, or reported as alive or as
      having occurred during childhood (n = 8). Among deaths reported both in the SSH
      and DSS data, 94% of deaths classified as pregnancy related in the DSS data were
      also classified as such by siblings' survival histories. Only 70% of deaths
      classified as not pregnancy related in the DSS data were also classified as such
      by siblings' survival histories. CONCLUSION: Misclassifications of pregnancy
      related deaths in retrospective adult mortality surveys may affect estimates of
      pregnancy-related mortality rates.

PMID- 23130913
TI  - Robustness in protein folding revealed by thermodynamics calculations.
AB  - Long-range intraprotein interactions play important roles in protein folding. In
      the present study, we use two variants of the B domain of protein A (BdpA
      F14W/G30A and BdpA_ds) and two variants of the Trp cage (TC5b_P1 and TC5b_P2) as
      models to investigate how long-range hydrophobic interactions affect protein
      tertiary and secondary structures. The mutation of the selected residues (BdpA
      F14W/G30A) or the change in the sequence order of Helix1 and Helix2 (BdpA_ds)
      changes detailed hydrophobic interactions. However, this change does not alter
      the global three-helix-bundle structure of BdpA and the overall shape of the
      folding free-energy landscape. It does affect the formation and stability of
      individual secondary structures. Similarly, the addition of an extra segment to
      the C-terminus of Trp-cage increases the number of long-range hydrophobic
      interactions without making any significant change of the native structure of Trp
      cage. These results show the robustness of the overall protein folding, where
      rather large sequence changes exert significant influences on secondary but not
      tertiary structures.

PMID- 23130914
TI  - The role of order-disorder transitions in the quest for molecular multiferroics:
      structural and magnetic neutron studies of a mixed valence iron(II)-iron(III)
      formate framework.
AB  - Neutron diffraction studies have been carried out to shed light on the
      unprecedented order-disorder phase transition (ca. 155 K) observed in the mixed
      valence iron(II)-iron(III) formate framework compound
      [NH(2)(CH(3))(2)](n)[Fe(III)Fe(II)(HCOO)(6)](n). The crystal structure at 220 K
      was first determined from Laue diffraction data, then a second refinement at 175
      K and the crystal structure determination in the low temperature phase at 45 K
      were done with data from the monochromatic high resolution single crystal
      diffractometer D19. The 45 K nuclear structure reveals that the phase transition
      is associated with the order-disorder of the dimethylammonium counterion that is
      weakly anchored in the cavities of the [Fe(III)Fe(II)(HCOO)(6)](n) framework. In
      the low-temperature phase, a change in space group from P31c to R3c occurs,
      involving a tripling of the c-axis due to the ordering of the dimethylammonium
      counterion. The occurrence of this nuclear phase transition is associated with an
      electric transition, from paraelectric to antiferroelectric. A combination of
      powder and single crystal neutron diffraction measurements below the magnetic
      order transition (ca. 37 K) has been used to determine unequivocally the magnetic
      structure of this Neel N-Type ferrimagnet, proving that the ferrimagnetic
      behavior is due to a noncompensation of the different Fe(II) and Fe(III) magnetic
      moments.

PMID- 23130918
TI  - Prevalence, comorbidity and stability of post-traumatic stress disorder and
      anxiety and depression symptoms after exposure to physical assault: an 8-year
      prospective longitudinal study.
AB  - BACKGROUND: There is a lack of prospective longitudinal studies focusing
      specifically on the victims exposed to physical violence by a perpetrator other
      than a family member. AIMS: To assess the prevalence and comorbidity of post
      traumatic stress disorder (PTSD) and anxiety and depression symptoms and the
      stability of symptoms, in a population of victims of non-domestic physical
      violence through 8 years. METHOD: This study had a single group longitudinal
      design with four repeated measures-the first as soon as possible after the
      exposure (n = 143 at T1), the second 3 months later (n = 94 at T2), the third
      after 1 year (n = 73 at T3) and the fourth after 8 years (n = 47 at T4).
      Questionnaires used were Impact of Event Scale-15 and 22 (IES-15 and 22), Post
      Traumatic Symptom Scale-10 (PTSS-10) and the Hopkins Symptoms Check List (HSCL
      25). RESULTS: Probable PTSD cases measured with IES-15 were 33.6% at T1, 30.9 at
      T2, 30.1% at T3 (12 months) and 19.1% at T4 (8 years), while probable anxiety and
      depression cases measured with HSCL-25 were 42.3% at T1, 35.5% at T2, 35.6% at T3
      and 23.4% at T4. The estimated probability of recovery from PTSD symptoms during
      the 8 years is 52%, whereas the corresponding finding concerning anxiety and
      depression is 43%. CONCLUSION: The consequences of exposure to physical assault
      by strangers need to be given more attention as a severe risk of chronic mental
      health problems.

PMID- 23130919
TI  - Bifid mandibular canals and the factors associated with their presence: a medical
      computed tomography evaluation in a Taiwanese population.
AB  - OBJECTIVES: To examine distribution of bifid mandibular canals in a Taiwanese
      population and to evaluate factors contributing to the phenomenon. MATERIAL AND
      METHODS: Computed tomographic images from 173 subjects (97 females and 76 males)
      were obtained using a 64-slice multidetector computerized tomography system, and
      the presence of bifid mandibular canals, as well as their widths and lengths, was
      examined. Association of length of bifid canals with possible contributing
      factors, including gender, age, and side of presentation, as well as size of
      cross-sectional bony area of mandible along the long axis of mandibular canal,
      was evaluated. RESULTS: Bifid mandibular canals, with mean values of 10.1 and 0.9
      mm in length and width, were found in 53 (30.6%) of 173 patients and 64 (18.5%)
      of 346 hemi-mandibles. Bifid canals appeared more frequently and tend to
      penetrate mandible with greater lengths in males if compared with those in
      females. When males were compared with females and when mandibles with bifid
      canals were compared with ones without, the former tend to present with larger
      bony area at corresponding levels of cross-sectional plane than the later,
      respectively. By regression analysis, significant association was found between
      length of bifid canals and gender, side of hemi-mandible, and bony area at mid
      zone of mandibular canal. CONCLUSIONS: Bifid canals were observed in 30.6% of
      subjects and 18.5% of hemi-mandibles. Significant association between length of
      bifid canals and gender, side of hemi-mandible, and cross-sectional bony area of
      mandible was observed.

PMID- 23130920
TI  - Metabolic profiling: are we en route to better diagnostic tests for cancer?

PMID- 23130921
TI  - Genome-based diagnostics and predictive tools: a new epoch for breast cancer
      management.

PMID- 23130922
TI  - Early evaluation of targeted drugs using dynamic contrast-enhanced
      ultrasonography for personalized medicine.

PMID- 23130924
TI  - Current treatment strategies with lenalidomide in multiple myeloma and future
      perspectives.
AB  - Lenalidomide is an immunomodulatory drug derived from thalidomide, developed to
      maximize its anti-inflammatory and antineoplastic properties while reducing
      toxicity. Lenalidomide administered orally at 25 mg/d on days 1-21 of 28-day
      cycles plus dexamethasone is indicated for the treatment of relapsed/refractory
      multiple myeloma patients, who received at least one prior therapy. In the
      pivotal MM-009 and MM-010 Phase III registration trials, lenalidomide
      dexamethasone, when compared with placebo-dexamethasone, significantly improved
      response rate (60 vs 20%, respectively), time-to-progression and survival. The
      most common adverse events included hematologic toxicity and venous
      thromboembolism. The drug is currently being investigated for the treatment of
      newly diagnosed myeloma and, in association with chemotherapy drugs
      (cyclophosphamide and melphalan) or novel agents (bortezomib, carfilzomib and
      elotuzumab), for the development of highly active combination regimens.

PMID- 23130925
TI  - Custirsen (OGX-011): a second-generation antisense inhibitor of clusterin in
      development for the treatment of prostate cancer.
AB  - Clusterin is a stress-induced cytoprotective chaperone that confers broad
      spectrum treatment resistance and is overexpressed across a number of cancers.
      custirsen (OGX-011) is a promising novel second-generation antisense inhibitor of
      clusterin in clinical development. This article describes the mechanism of action
      and safety profile of OGX-011 and details the Phase I and II results in human
      solid organ malignancies. Two Phase III registration trials are currently under
      recruitment evaluating OGX-011 in combination with chemotherapy in patients with
      metastatic castration-resistant prostate cancer. These studies not only have the
      potential to significantly alter the standard of care in prostate cancer, but
      would also endorse a new class of targets and targeted therapy approach for
      cancer.

PMID- 23130926
TI  - Single circulating tumor cell profiling: a new perspective for targeted therapy?
AB  - Evaluation of: Powell AA, Talasaz AH, Zhang H et al. Single cell profiling of
      circulating tumor cells: transcriptional heterogeneity and diversity from breast
      cancer cell lines. PLoS ONE 7(5), e33788 (2012). Circulating tumor cells (CTCs)
      may represent a possible useful tool to better define the prognosis of patients.
      The presence of CTCs can help to predict an increased risk for disease relapse,
      and they might be an early marker for treatment efficacy that could help in
      deciding treatment continuation. Cancer metastasis occurs when cells, shed from
      the primary tumor, enter the circulation and begin to grow in distant locations
      around the body. In metastatic stages, shed cells may differ from those of the
      primary tumor, as the tumor phenotype can change during the course of the
      disease. It is important to identify relevant targets expressed on these cells to
      provide clinical information on therapy choice, efficacy and drug resistance.
      Many efforts are now devoted to the characterization of the single cell. This
      article focuses on the possibility of profiling single CTCs in patients with
      breast cancer.

PMID- 23130927
TI  - Chromosomal instability, aneuploidy and routine high-resolution DNA content
      analysis in oral cancer risk evaluation.
AB  - Carcinogen exposure of the oral cavity is thought to create an extensive 'field
      cancerization'. According to this model, a very early precursor of oral cancer is
      a patch of normal-appearing mucosa in which stem cells share genetic/genomic
      aberrations. These precancerous fields then become clinically visible as white
      and red lesions (leuko- and erythro-plakias), which represent the vast majority
      of the oral potentially malignant disorders. This review focuses on aneuploidy
      (where it is from) and on biomarkers associated with DNA aneuploidy in oral
      mucosa and oral potentially malignant disorders, as detected by DNA image and
      flow cytometry. Data from the literature strongly support the association of DNA
      ploidy with dysplasia. However, work is still needed to prove the clinical value
      of DNA ploidy in large-scale prospective studies. Using high-resolution DNA flow
      cytometry with fresh/frozen material and the degree of DNA aneuploidy (DNA Index)
      might improve the prediction of risk of oral cancer development.

PMID- 23130929
TI  - HAMLET: functional properties and therapeutic potential.
AB  - Human alpha-lactalbumin made lethal to tumor cells (HAMLET) is the first member
      in a new family of protein-lipid complexes that kills tumor cells with high
      selectivity. The protein component of HAMLET is alpha-lactalbumin, which in its
      native state acts as a substrate specifier in the lactose synthase complex,
      thereby defining a function essential for the survival of lactating mammals. In
      addition, alpha-lactalbumin acquires tumoricidal activity after partial unfolding
      and binding to oleic acid. The lipid cofactor serves the dual role as a
      stabilizer of the altered fold of the protein and a coactivator of specific steps
      in tumor cell death. HAMLET is broadly tumoricidal, suggesting that the complex
      identifies conserved death pathways suitable for targeting by novel therapies.
      Sensitivity to HAMLET is defined by oncogene expression including Ras and c-Myc
      and by glycolytic enzymes. Cellular targets are located in the cytoplasmic
      membrane, cytoskeleton, mitochondria, proteasomes, lysosomes and nuclei, and
      specific signaling pathways are rapidly activated, first by interactions of
      HAMLET with the cell membrane and subsequently after HAMLET internalization.
      Therapeutic effects of HAMLET have been demonstrated in human skin papillomas and
      bladder cancers, and HAMLET limits the progression of human glioblastomas, with
      no evidence of toxicity for normal brain or bladder tissue. These findings open
      up new avenues for cancer therapy and the understanding of conserved death
      responses in tumor cells.

PMID- 23130930
TI  - Targeting the latest hallmark of cancer: another attempt at 'magic bullet' drugs
      targeting cancers' metabolic phenotype.
AB  - The metabolism of tumors is remarkably different from the metabolism of
      corresponding normal cells and tissues. Metabolic alterations are initiated by
      oncogenes and are required for malignant transformation, allowing cancer cells to
      resist some cell death signals while producing energy and fulfilling their
      biosynthetic needs with limiting resources. The distinct metabolic phenotype of
      cancers provides an interesting avenue for treatment, potentially with minimal
      side effects. As many cancers show similar metabolic characteristics, drugs
      targeting the cancer metabolic phenotype are, perhaps optimistically, expected to
      be 'magic bullet' treatments. Over the last few years there have been a number of
      potential drugs developed to specifically target cancer metabolism. Several of
      these drugs are currently in clinical and preclinical trials. This review
      outlines examples of drugs developed for different targets of significance to
      cancer metabolism, with a focus on small molecule leads, chemical biology and
      clinical results for these drugs.

PMID- 23130931
TI  - Update on thyroid cancer treatment.
AB  - Surgery and radioiodine therapy are usually effective for most patients with
      differentiated thyroid cancer. However, poorly differentiated and anaplastic
      thyroid carcinomas represent a challenge to physicians on the basis of the
      current cancer treatment modalities. These cancer subtypes are often lethal and
      refractory to radioiodine therapy as well as most of the common chemotherapy
      drugs. Several kinase inhibitors are promising targeted therapies for these
      malignancies; however, clinical trials involving these drugs have provided
      controversial results and their clinical use is still under debate. Advanced
      medullary thyroid carcinomas may also be refractory to conventional therapies and
      novel kinase inhibitors may also be useful to control tumor progression in
      certain patients. Novel evidence is emerging that thyroid cancer is a stem cell
      disease, thereby implying that the driving force of thyroid cancers is a subset
      of undifferentiated cells (thyroid cancer stem cells) with unlimited growth
      potential and resistance to conventional therapeutic regimens. Thyroid cancer
      stem cells have been proposed as responsible for tumor invasiveness, metastasis,
      relapse and differentiation. Therefore, drugs that selectively target these cells
      could serve as a cornerstone in the treatment of poorly differentiated thyroid
      cancer.

PMID- 23130932
TI  - EDIM-TKTL1 blood test: a noninvasive method to detect upregulated glucose
      metabolism in patients with malignancies.
AB  - AIM: To determine whether the TKTL1 protein epitope detection in monocytes (EDIM)
      test allows detection of upregulated glucose metabolism in malignancies.
      MATERIALS & METHODS: The EDIM-TKTL1 blood test was conducted in 240 patients with
      17 different confirmed or suspected malignancies. Test scores were compared with
      (18)F-fluoro-2-deoxy-D-glucose (FDG)-PET/computed tomography (CT) results.
      RESULTS: EDIM-TKTL1 score and FDG-PET results showed a concordance of 90% with a
      sensitivity of 94% and specificity of 81%. Including CT data, all values were
      enhanced. A subgroup analysis of non-small-cell lung cancer patients showed a
      significant correlation between the EDIM-TKTL1 score and the primary tumor size
      determined by FDG-PET/CT. CONCLUSION: EDIM-TKTL1 blood test revealed good
      concordance with FDG-PET/CT results in patients with malignancies demonstrating
      its efficacy to detect upregulation of glucose metabolism in primary tumors or
      metastases.

PMID- 23130933
TI  - Boron neutron capture therapy for glioblastoma multiforme: enhanced drug delivery
      and antitumor effect following blood-brain barrier disruption induced by focused
      ultrasound.
AB  - AIM: This study investigated whether the efficacy of boron neutron capture
      therapy was enhanced by means of intravenous administration of
      boronophenylalanine (BPA) with blood-brain barrier disruption induced by focused
      ultrasound (FUS). MATERIALS & METHODS: BPA was administered, followed by pulsed
      FUS, and the boron concentration in the treated brains was quantified by
      inductively coupled plasma mass spectroscopy. Growth of the firefly luciferase
      labeled glioma cells was monitored through noninvasive biophotonic imaging.
      Finally, the brain tissue was histologically examined after sacrifice. RESULTS:
      Compared with the nonsonicated tumor group, animals treated with an injection of
      500 mg/kg of BPA followed by FUS exhibited not only significantly increased
      accumulation of the drug at the sonicated tumor site, but also a significantly
      elevated tumor-to-normal brain drug ratio (p < 0.05). DISCUSSION: The data
      demonstrated that FUS significantly enhances the tumor-to-normal brain drug ratio
      in the sonicated tumor and subsequently the efficacy of boron neutron capture
      therapy.

PMID- 23130928
TI  - Dendritic cell-based vaccines: barriers and opportunities.
AB  - Dendritic cells (DCs) have several characteristics that make them an ideal
      vehicle for tumor vaccines, and with the first US FDA-approved DC-based vaccine
      in use for the treatment of prostate cancer, this technology has become a
      promising new therapeutic option. However, DC-based vaccines face several
      barriers that have limited their effectiveness in clinical trials. A major
      barrier includes the activation state of the DC. Both DC lineage and maturation
      signals must be selected to optimize the antitumor response and overcome
      immunosuppressive effects of the tumor microenvironment. Another barrier to
      successful vaccination is the selection of target antigens that will activate
      both CD8(+) and CD4(+) T cells in a potent, immune-specific manner. Finally,
      tumor progression and immune dysfunction limit vaccine efficacy in advanced
      stages, which may make DC-based vaccines more efficacious in treating early-stage
      disease. This review underscores the scientific basis and advances in the
      development of DC-based vaccines, focuses on current barriers to success and
      highlights new research opportunities to address these obstacles.

PMID- 23130935
TI  - Use of real-time quantitative PCR to document successful treatment of Mycoplasma
      haemocanis infection with doxycycline in a dog.
AB  - An 8-year-old Jack Russell Terrier was diagnosed with hemolytic anemia caused by
      hemoplasmosis 4 years following splenectomy. Quantitative real-time PCR (qPCR)
      analysis was used initially to confirm infection with Mycoplasma haemocanis and
      subsequently to monitor and direct medical therapy. Doxycycline was administered
      beyond resolution of clinical signs until hemoplasma DNA could no longer be
      detected by qPCR. The dog remained clinically healthy and hemoplasma-negative 8
      months following cessation of therapy. Canine hemoplasmosis should remain as a
      differential diagnosis for hemolytic anemia in dogs, particularly those that are
      splenectomized or immunocompromised, even in geographic regions where prevalence
      of infection is low. Prolonged doxycycline administration has been shown by qPCR
      to lead to sustained absence of detectable infection and should be considered as
      a first line treatment for canine hemoplasmosis.

PMID- 23130937
TI  - Conscious sedation and anesthesia in the cardiac electrophysiology laboratory.
AB  - Adequate anesthesia is important for performing EP procedures such as catheter
      ablation and implantation of cardiac devices. A wide range of anesthesia options
      are available, and all can be safely administered in EP laboratory with proper
      monitoring, drug selection, airway management equipment, and trained personnel.
      In addition to knowing the patient's clinical status, a thorough understanding of
      the clinical pharmacology of each anesthetic agent is essential in order to
      select appropriate drug among a variety of available anesthetics, to monitor for
      adverse effects, and to ensure adequate sedation and anesthesia for a
      comfortable, safe, and successful procedure. After a general strategy of
      anesthesia is planned, an individual anesthetic agent or combination of agents
      can be selected based on their pharmacological properties while keeping in mind
      the desired sedation/anesthesia requirements. Since anesthetics are often used in
      combination, the synergistic interaction of several anesthetic agents
      (infiltrative, parenteral, and/or inhaled) needs to be considered. Further
      attention also needs to be paid to the interaction between anesthetics and other
      existing medications. Finally, all care providers should work collaboratively and
      communicate frequently to provide a safe and effective anesthesia.

PMID- 23130936
TI  - Evaluating mitochondrial DNA variation in autism spectrum disorders.
AB  - Despite the increasing speculation that oxidative stress and abnormal energy
      metabolism may play a role in Autism Spectrum Disorders (ASD), and the
      observation that patients with mitochondrial defects have symptoms consistent
      with ASD, there are no comprehensive published studies examining the role of
      mitochondrial variation in autism. Therefore, we have sought to comprehensively
      examine the role of mitochondrial DNA (mtDNA) variation with regard to ASD risk,
      employing a multi-phase approach. In phase 1 of our experiment, we examined 132
      mtDNA single-nucleotide polymorphisms (SNPs) genotyped as part of our genome-wide
      association studies of ASD. In phase 2 we genotyped the major European
      mitochondrial haplogroup-defining variants within an expanded set of autism
      probands and controls. Finally in phase 3, we resequenced the entire mtDNA in a
      subset of our Caucasian samples (~400 proband-father pairs). In each phase we
      tested whether mitochondrial variation showed evidence of association to ASD.
      Despite a thorough interrogation of mtDNA variation, we found no evidence to
      suggest a major role for mtDNA variation in ASD susceptibility. Accordingly,
      while there may be attractive biological hints suggesting the role of
      mitochondria in ASD our data indicate that mtDNA variation is not a major
      contributing factor to the development of ASD.

PMID- 23130939
TI  - Seasonal effect on infants' sleep regulation: a preliminary study in a
      Mediterranean climate.
AB  - Infants' sleep-wake rhythms are influenced by multiple factors, including
      developmental and contextual aspects, as well as circadian cycles. Empirical
      studies that address the seasonal impact on infants' sleep are scarce. The
      present study examined aspects of sleep schedule and quality, comparing summer
      and winter months in a Mediterranean climate. This report is based on a
      convenience sample of 34 healthy 7-mo-olds, an age in which sleep is well
      consolidated and regulated compared with the first few months of life. Sleep was
      measured with actigraphy, in the home context. It was found that compared with
      winter, in the summer months, sleep onset occurred at a later hour, and more
      motor activity during sleep was detected. Although the overall sleep quality, as
      defined by sleep efficiency score, was similar in the two seasons, in the summer,
      more active sleep was observed. The authors discuss the finding in terms of
      circadian rhythms, developmental characteristics, as well as possible
      environmental factors and family routines, and call for more studies, in
      different climates and geographical zones, and in different developmental
      periods.

PMID- 23130938
TI  - SOLITAIRETM with the intention for thrombectomy (SWIFT) trial: design of a
      randomized, controlled, multicenter study comparing the SOLITAIRETM Flow
      Restoration device and the MERCI Retriever in acute ischaemic stroke.
AB  - RATIONALE: Self-expanding stent retrievers are a promising new device class
      designed for rapid flow restoration in acute cerebral ischaemia. The SOLITAIRETM
      Flow Restoration device (SOLITAIRE) has shown high rates of recanalization in
      preclinical models and in uncontrolled clinical series. AIMS: (1) To demonstrate
      non-inferiority of SOLITAIRE compared with a legally marketed device, the MERCI
      Retrieval System(r); (2) To demonstrate safety, feasibility, and efficacy of
      SOLITAIRE in subjects requiring mechanical thrombectomy diagnosed with acute
      ischaemic stroke. DESIGN : Multicenter, randomized, prospective, controlled trial
      with blinded primary end-point ascertainment. STUDY PROCEDURES: Key entry
      criteria include: age 22-85; National Institute of Health Stroke Scale (NIHSS)
      >=8 and <30; clinical and imaging findings consistent with acute ischaemic
      stroke; patient ineligible or failed intravenous tissue plasminogen activator;
      accessible occlusion in M1 or M2 middle cerebral artery, internal carotid artery,
      basilar artery, or vertebral artery; and patient able to be treated within 8 h of
      onset. Sites first participate in a roll-in phase, treating two patients with the
      SOLITAIRE device, before proceeding to the randomized phase. In patients
      unresponsive to the initially assigned therapy, after the angiographic component
      of the primary end-point is ascertained (reperfusion with the initial assigned
      device), rescue therapy with other reperfusion techniques is permitted. OUTCOMES:
      The primary efficacy end-point is successful recanalization with the assigned
      study device (no use of rescue therapy) and with no symptomatic intracranial
      haemorrhage. Successful recanalization is defined as achieving Thrombolysis In
      Myocardial Ischemia 2 or 3 flow in all treatable vessels. The primary safety end
      point is the incidence of device-related and procedure-related serious adverse
      events. A major secondary efficacy end-point is time to achieve initial
      recanalization. Additional secondary end-points include clinical outcomes at 90
      days and radiologic haemorrhagic transformation.

PMID- 23130940
TI  - Light-dependent regulation of ascorbate in tomato by a monodehydroascorbate
      reductase localized in peroxisomes and the cytosol.
AB  - Ascorbate is a powerful antioxidant in plants, and its levels are an important
      quality criteria in commercial species. Factors influencing these levels include
      environmental variations, particularly light, and the genetic control of its
      biosynthesis, recycling and degradation. One of the genes involved in the
      recycling pathway encodes a monodehydroascorbate reductase (MDHAR), an enzyme
      catalysing reduction of the oxidized radical of ascorbate, monodehydroascorbate,
      to ascorbate. In plants, MDHAR belongs to a multigene family. Here, we report the
      presence of an MDHAR isoform in both the cytosol and peroxisomes and show that
      this enzyme negatively regulates ascorbate levels in Solanum lycopersicum
      (tomato). Transgenic lines overexpressing MDHAR show a decrease in ascorbate
      levels in leaves, whereas lines where MDHAR is silenced show an increase in these
      levels in both fruits and leaves. Furthermore, the intensity of these differences
      is light dependent. The unexpected effect of this MDHAR on ascorbate levels
      cannot be explained by changes in the expression of Smirnoff-Wheeler pathway
      genes, or the activity of enzymes involved in degradation (ascorbate peroxidase)
      or recycling of ascorbate (dehydroascorbate reductase and glutathione reductase),
      suggesting a previously unidentified mechanism regulating ascorbate levels.

PMID- 23130942
TI  - Response to atrial extrastimulus during supraventricular tachycardia: what is the
      mechanism?
AB  - We describe a case illustrating the potential challenges in distinguishing AV
      nodal reentry tachycardia (AVNRT) from automatic junctional tachycardia (JT).
      While an early atrial extrastimulus advanced the next His and ventricular
      depolarization without tachycardia termination, suggesting JT, other features
      indicated the correct diagnosis of AVNRT. This teaching case demonstrates a novel
      exception to a recently reported diagnostic pacing maneuver and illustrates the
      importance of considering response to multiple maneuvers in reaching a diagnosis
      of SVT mechanism.

PMID- 23130941
TI  - PCA3 noncoding RNA is involved in the control of prostate-cancer cell survival
      and modulates androgen receptor signaling.
AB  - BACKGROUND: PCA3 is a non-coding RNA (ncRNA) that is highly expressed in prostate
      cancer (PCa) cells, but its functional role is unknown. To investigate its
      putative function in PCa biology, we used gene expression knockdown by small
      interference RNA, and also analyzed its involvement in androgen receptor (AR)
      signaling. METHODS: LNCaP and PC3 cells were used as in vitro models for these
      functional assays, and three different siRNA sequences were specifically designed
      to target PCA3 exon 4. Transfected cells were analyzed by real-time qRT-PCR and
      cell growth, viability, and apoptosis assays. Associations between PCA3 and the
      androgen-receptor (AR) signaling pathway were investigated by treating LNCaP
      cells with 100 nM dihydrotestosterone (DHT) and with its antagonist (flutamide),
      and analyzing the expression of some AR-modulated genes (TMPRSS2, NDRG1, GREB1,
      PSA, AR, FGF8, CdK1, CdK2 and PMEPA1). PCA3 expression levels were investigated
      in different cell compartments by using differential centrifugation and qRT-PCR.
      RESULTS: LNCaP siPCA3-transfected cells significantly inhibited cell growth and
      viability, and increased the proportion of cells in the sub G0/G1 phase of the
      cell cycle and the percentage of pyknotic nuclei, compared to those transfected
      with scramble siRNA (siSCr)-transfected cells. DHT-treated LNCaP cells induced a
      significant upregulation of PCA3 expression, which was reversed by flutamide. In
      siPCA3/LNCaP-transfected cells, the expression of AR target genes was
      downregulated compared to siSCr-transfected cells. The siPCA3 transfection also
      counteracted DHT stimulatory effects on the AR signaling cascade, significantly
      downregulating expression of the AR target gene. Analysis of PCA3 expression in
      different cell compartments provided evidence that the main functional roles of
      PCA3 occur in the nuclei and microsomal cell fractions. CONCLUSIONS: Our findings
      suggest that the ncRNA PCA3 is involved in the control of PCa cell survival, in
      part through modulating AR signaling, which may raise new possibilities of using
      PCA3 knockdown as an additional therapeutic strategy for PCa control.

PMID- 23130943
TI  - Auricular acupressure for pain relief in adolescents with dysmenorrhea: a placebo
      controlled study.
AB  - OBJECTIVES: Primary dysmenorrhea is a common problem among menstruating
      adolescents and young women. It may cause physical distress and result in school
      absenteeism and reduced physical activity. This study aimed to evaluate the
      effects of auricular acupressure on menstrual pain and distress in adolescents
      with dysmenorrhea. DESIGN: A single-blind, placebo-controlled design was used.
      SETTING/LOCATION: Participants were obtained from one senior high school in
      northern Taiwan. SUBJECTS: One hundred and thirteen (113) adolescent participants
      with primary dysmenorrhea were recruited and assigned to the experimental or
      control group by a coin toss. INTERVENTION: The experimental group received
      auricular acupressure applied to six true acupoints (shenmen, Kidney, Liver,
      Internal Genitals, Central Rim, and Endocrine). The control group received six
      sham acupoints without effects on dysmenorrhea. All participants were instructed
      to press each acupoint for 1 minute, 4 times a day for 2 days. OUTCOME MEASURES:
      The outcomes were assessed by rating dysmenorrhea severity on a visual analogue
      scale (VAS) and using the Short-Form McGill Pain Questionnaire (SF-MPQ) and
      Menstrual Distress Questionnaire (MDQ). RESULTS: Between-group differences were
      found in VAS and MDQ after the interventions. Within-group differences were found
      in the score changes of VAS, MDQ, and SF-MPQ during the interventions for both
      groups. CONCLUSIONS: Auricular acupressure relieves menstrual pain and distress
      in high-school adolescents. The findings may serve as a basis for using auricular
      acupressure to treat dysmenorrhea in adolescents. There was pain reduction with
      sham as well as with true acupoint acupressure, but the latter was significantly
      greater. The sham acupoint may not be used as a control for auricular acupoint
      and qualitative evaluation of dysmenorrhea should be added to the evaluation by
      SF-MPQ in future studies.

PMID- 23130945
TI  - Correlation between surface stress and apparent Young's modulus of top-down
      silicon nanowires.
AB  - In this work, we report experimental evidence of surface stress effects on the
      mechanical properties of silicon nanostructures. As-fabricated, top-down silicon
      nanowires (SiNWs) are bent up without any applied force. This self-buckling is
      related to the surface relaxation that reaches an equilibrium with bulk
      deformation due to the material elasticity. We measure the SiNW self-deformation
      by atomic force microscopy (AFM), and we apply a simple physical model in order
      to give an estimation of the surface stress. If the equilibrium is altered by a
      nanoforce, applied by an AFM tip, nanowires find a new equilibrium condition
      bending down (mechanical bistability). In this work, for the first time, we
      report a clear and quantitative relationship between the SiNWs' apparent Young's
      modulus, measured by force-deflection spectroscopy, and the estimated value of
      surface stress, obtained by self-buckling measurements taking into account the
      Young's modulus of bulk silicon. This is an experimental confirmation that the
      surface stress is fundamental in determining mechanical properties of SiNWs, and
      that the elastic behavior of nanostructures strongly depends on their surfaces.

PMID- 23130946
TI  - Polarization tunable, multicolor emission from core-shell photonic III-V
      semiconductor nanowires.
AB  - We demonstrate luminescence from both the core and the shell of III-V
      semiconductor photonic nanowires by coupling them to plasmonic silver
      nanoparticles. This demonstration paves the way for increasing the quantum
      efficiency of large surface area nanowire light emitters. The relative emission
      intensity from the core and the shell is tuned by varying the polarization of the
      excitation source since their polarization response can be independently
      controlled. Independent control on emission wavelength and polarization
      dependence of emission from core-shell nanowire heterostructures opens up
      opportunities that have not yet been imagined for nanoscale polarization
      sensitive, wavelength-selective, or multicolor photonic devices based on single
      nanowires or nanowire arrays.

PMID- 23130947
TI  - A self-powered acetaldehyde sensor based on biofuel cell.
AB  - Acetaldehyde is recognized as a type of organic environmental pollutant all over
      the world, which makes the sensitive, rapid, simple and low-cost detection of
      acetaldehyde urgent and significant. Inspired by the biological principle of
      feedback modulation, we have developed a novel and effective self-powered device
      for aqueous acetaldehyde detection. In this self-powered device, an ethanol/air
      enzymatic biofuel cell (BFC) served as the core component, which showed the
      maximum power output density of 28.5 MUW cm(-2) at 0.34 V and the open circuit
      potential (V(oc)) of 0.64 V. The product of ethanol oxidation, acetaldehyde,
      would counteract the electrocatalysis at the bioanode and further decrease the
      power output of the BFC. Based on such principles, the fabricated acetaldehyde
      sensor exhibited excellent selectivity with wide linear range (5-200 MUM) and low
      detection limit (1 MUM), which conforms to the criteria provided by the World
      Health Organisation (WHO). In addition, the sensor fabrication is simple, fast,
      inexpensive, and user-friendly, and the detection process is convenient,
      efficient, and time-saving, requiring no complicated equipment. These make such
      self-powered acetaldehyde sensors feasible and practical for detecting aqueous
      acetaldehyde, particularly in the field of quality control and monitoring aimed
      at water resource protection.

PMID- 23130948
TI  - Near-infrared emitting CdTe0.5Se0.5/Cd0.5Zn0.5S quantum dots: synthesis and
      bright luminescence.
AB  - We present how CdTe0.5Se0.5 cores can be coated with Cd0.5Zn0.5S shells at
      relatively low temperature (around 200 degrees C) via facile synthesis using
      organic ammine ligands. The cores were firstly fabricated via a less toxic
      procedure using CdO, trioctylphosphine (TOP), Se, Te, and trioctylamine. The
      cores with small sizes (3.2-3.5 nm) revealed green and yellow photoluminescence
      (PL) and spherical morphologies. Hydrophobic core/shell CdTe0.5Se0.5/Cd0.5Zn0.5S
      quantum dots (QDs) with tunable PL between green and near-infrared (a maximum PL
      peak wavelength of 735 nm) were then created through a facile shell coating
      procedure using trioctylphosphine selenium with cadmium and zinc acetate. The QDs
      exhibited high PL efficiencies up to 50% because of the formation of a protective
      Cd0.5Zn0.5S shell on the CdTe0.5Se0.5 core, even though the PL efficiency of the
      cores is low (<=1%). Namely, the slow growth process of the shell plays an
      important role for getting high PL efficiencies. The properties of the QDs are
      largely determined by the properties of CdTe0.5Se0.5 cores and shells preparation
      conditions such as reaction temperature and time. The core/shell QDs exhibited a
      small size diameter. For example, the average diameter of the QDs with a PL peak
      wavelength of 735 nm is 6.1 nm. Small size and tunable bright PL makes the QDs
      utilizable as bioprobes because the size of QD-based bioprobes is considered as
      the major limitation for their broad applications in biological imaging.

PMID- 23130953
TI  - Systematic review and meta-analysis of the associations between indoor air
      pollution and tuberculosis.
AB  - OBJECTIVE: Half the world's population uses biomass fuel for their daily needs
      but the resultant emissions and indoor air pollution (IAP) are harmful to health.
      So far, evidence for a link between IAP and tuberculosis (TB) was insufficient.
      We report an updated systematic review due to recent increase in the evidence and
      growing interest in testing interventions. METHODS: Systematic search of PubMed
      (including Medline), CAB abstracts (through Ovid SP) and Web of Knowledge using
      the following search terms: 'IAP or biomass or cooking smoke' and 'TB'. 452
      abstracts were reviewed, and only 12 articles were deemed to be reporting the
      effects of IAP on TB and were taken forward to full review, and one study was
      added through hand search of references. Data on measures of effect of IAP on TB
      were extracted, and meta-analysis was carried out to estimate pooled measures of
      effect. RESULTS: Thirteen studies have reported investigating association between
      IAP and TB since 1996. TB cases are more likely to be exposed to IAP than healthy
      controls (pooled OR 1.30; 95% CI, 1.04-1.62; P = 0.02). CONCLUSIONS: There is
      increasingly strong evidence for an association between IAP and TB. Further
      studies are needed to understand the burden of TB attributable to IAP.
      Interventions such as clean cook stoves to reduce the adverse effects of IAP
      merit rigorous evaluation, particularly in Africa and India where the prevalence
      of IAP and TB is high.

PMID- 23130944
TI  - Aquaporin-2 regulation in health and disease.
AB  - Aquaporin-2 (AQP2), the vasopressin-regulated water channel of the renal
      collecting duct, is dysregulated in numerous disorders of water balance in people
      and animals, including those associated with polyuria (urinary tract obstruction,
      hypokalemia, inflammation, and lithium toxicity) and with dilutional hyponatremia
      (syndrome of inappropriate antidiuresis, congestive heart failure, cirrhosis).
      Normal regulation of AQP2 by vasopressin involves 2 independent regulatory
      mechanisms: (1) short-term regulation of AQP2 trafficking to and from the apical
      plasma membrane, and (2) long-term regulation of the total abundance of the AQP2
      protein in the cells. Most disorders of water balance are the result of
      dysregulation of processes that regulate the total abundance of AQP2 in
      collecting duct cells. In general, the level of AQP2 in a collecting duct cell is
      determined by a balance between production via translation of AQP2 mRNA and
      removal via degradation or secretion into the urine in exosomes. AQP2 abundance
      increases in response to vasopressin chiefly due to increased translation
      subsequent to increases in AQP2 mRNA. Vasopressin-mediated regulation of AQP2
      gene transcription is poorly understood, although several transcription factor
      binding elements in the 5' flanking region of the AQP2 gene have been identified,
      and candidate transcription factors corresponding to these elements have been
      discovered in proteomics studies. Here, we review progress in this area and
      discuss elements of vasopressin signaling in the collecting duct that may impinge
      on regulation of AQP2 in health and in the context of examples of polyuric
      diseases.

PMID- 23130954
TI  - Phytosterols esterified with conjugated linoleic acid. In vitro intestinal
      digestion and interaction on cholesterol bioaccessibility.
AB  - Intestinal in vitro digestion of phytosterols esterified with conjugated linoleic
      acid (PS-CLA) was performed to study (1) the potential bioaccessibility of the
      released bioactive-lipid products and (2) the interference with cholesterol
      bioaccessibility. Commercial food-grade PS ester (PS-C) was assayed as reference.
      Hydrolysis of PS-CLA by digestive enzymes was similar to that of PS-C (51 and
      47%, respectively), most lipids products being mainly included in the
      bioaccessible fraction, namely, the micellar phase (MP). Control assays in the
      absence of PS esters showed most cholesterol solubilized within the MP, whereas a
      displacement of total cholesterol was caused from MP after digestion of PS esters
      (14 and 36% displacement for PS-CLA and PS-C, respectively), cholesterol being
      partially precipitated. Precipitated cholesterol was linearly related to a
      parallel precipitation of saturated-chain PS, mainly determined by sitosterol (R2
      = 0.936). The higher composition in sitosteryl esters of PS-C with respect to PS
      CLA might explain their different effects on cholesterol. Therefore, besides
      being a lipid delivery form of PS similar to other commercial esterified PS, the
      PS-CLA might have the additional advantage of being a lipid delivery form of CLA.
      Moreover, PS-CLA might hinder the bioaccessibility of cholesterol. Furthermore,
      the qualitative/quantitative profile in esterified PS forms might determine the
      magnitude of cholesterol interaction.

PMID- 23130955
TI  - Spectroscopic study of HNO3 dissociation on ice.
AB  - A detailed spectroscopic study of HNO(3):H(2)O binary amorphous mixtures, and of
      the adsorption of HNO(3) onto ice, is reported. Using a classical optics model,
      the extent of intermixing and of ionic dissociation of adsorbed HNO(3), which
      forms a strong acid with liquid water, is determined as a function of HNO(3)
      coverage and temperature. Even at temperatures as low as 45 K, where intermixing
      is limited to at most a few molecular layers at the interface, ionic dissociation
      of adsorbed HNO(3) is observed to be extensive. While some amount of molecularly
      adsorbed HNO(3) is observed at the surface of ice at 45 K, its ionic dissociation
      occurs irreversibly upon heating the ice substrate to 120 K. The molecularly
      adsorbed state of HNO(3) is not restored upon cooling, suggesting HNO(3) is a
      metastable entity at the surface of ice. Therefore, despite ionic dissociation of
      HNO(3) being thermodynamically favored, it appears to be kinetically inhibited at
      the surface of amorphous solid water at temperatures below 120 K.

PMID- 23130956
TI  - Carotenoid charge transfer states and their role in energy transfer processes in
      LH1-RC complexes from aerobic anoxygenic phototrophs.
AB  - Light-harvesting complexes ensure necessary flow of excitation energy into
      photosynthetic reaction centers. In the present work, transient absorption
      measurements were performed on LH1-RC complexes isolated from two aerobic
      anoxygenic phototrophs (AAPs), Roseobacter sp. COL2P containing the carotenoid
      spheroidenone, and Erythrobacter sp. NAP1 which contains the carotenoids
      zeaxanthin and bacteriorubixanthinal. We show that the spectroscopic data from
      the LH1-RC complex of Roseobacter sp. COL2P are very similar to those previously
      reported for Rhodobacter sphaeroides, including the transient absorption spectrum
      originating from the intramolecular charge-transfer (ICT) state of spheroidenone.
      Although the ICT state is also populated in LH1-RC complexes of Erythrobacter sp.
      NAP1, its appearance is probably related to the polarity of the
      bacteriorubixanthinal environment rather than to the specific configuration of
      the carotenoid, which we hypothesize is responsible for populating the ICT state
      of spheroidenone in LH1-RC of Roseobacter sp. COL2P. The population of the ICT
      state enables efficient S1/ICT-to-bacteriochlorophyll (BChl) energy transfer
      which would otherwise be largely inhibited for spheroidenone and
      bacteriorubixanthinal due to their low energy S1 states. In addition, the triplet
      states of these carotenoids appear well-tuned for efficient quenching of singlet
      oxygen or BChl-a triplets, which is of vital importance for oxygen-dependent
      organisms such as AAPs. 

PMID- 23130960
TI  - Unusual presentation of angiomyomatous hamartoma in an eight-month-old infant:
      case report and literature review.
AB  - BACKGROUND: Evaluation of palpable neck masses may be a diagnostic problem in
      pediatric patients, with differential diagnosis including congenital,
      inflammatory, tumoral and traumatic lesions. Ultrasonography is usually a
      satisfactory method to make a correct pre-operative evaluation of neck masses,
      although diagnosis is often challenging for the surgeon and the radiologist and
      sometimes only possible after a histopathological examination of the resected
      lesion. CASE PRESENTATION: We report an 8-month-old patient with a cervical,
      anterior midline mass. Ultrasonographic images showed features suggesting a
      partly cystic lesion, with a preoperative suspect of thyroglossal duct cyst.
      Histological examination, performed after surgical removal of the mass, led to a
      diagnosis of lymph node angiomyomatous hamartoma (AH). CONCLUSIONS: AH, a rarely
      occurring benign lymph node lesion, has been reported in the neck lateral region
      only twice. This case, presenting as a palpable neck midline mass, is the first
      reported case occurring in infancy. Although rare, AH should be included in the
      differential diagnosis of head and neck masses.

PMID- 23130961
TI  - Distribution of Aedes albopictus (Diptera, Culicidae) in southwestern Pacific
      countries, with a first report from the Kingdom of Tonga.
AB  - BACKGROUND: Aedes (Stegomyia) albopictus is currently one of the most notorious
      globally invasive mosquito species. Its medical importance is well documented,
      and its fast expansion throughout most continents is being monitored with
      concern. It is generally assumed that its expansion through the Western Pacific
      island countries has not progressed since its establishment in Fiji in 1989.
      However, the current status of Ae. albopictus in the Pacific region is largely
      unknown. FINDINGS: According to data from the literature and our own
      observations, Ae. albopictus is currently present in the following countries of
      the southern Pacific region: Papua New Guinea, Solomon Islands, Fiji, and the
      Kingdom of Tonga, where it was first detected in July 2011. It is absent from New
      Caledonia and French Polynesia where routine entomological surveillance is
      carried out, and was not detected during entomological work in 2007, either on
      the Cook Islands or on the Wallis and Futuna Islands. The species was not
      reported from American Samoa in 2004, but it is mentioned as probably present in
      Vanuatu. This is the first report of Ae. albopictus in Tonga. CONCLUSIONS: The
      introduction and establishment of Ae. albopictus in Tonga was expected due to the
      geographical proximity of this country to Fiji where the species is strongly
      established. The pathway of introduction is unknown. The expansion of Ae.
      albopictus in the Pacific region poses an increasing threat to public health
      given the role this mosquito plays as primary vector of emerging infectious
      diseases such as Chikungunya fever.

PMID- 23130957
TI  - Rationale for short course primaquine in Africa to interrupt malaria
      transmission.
AB  - Following the recent successes of malaria control in sub-Saharan Africa, the
      gametocytocidal drug primaquine needs evaluation as a tool to further reduce the
      transmission of Plasmodium falciparum malaria. The drug has scarcely been used in
      Africa because of concerns about its safety in people with glucose-6-phosphate
      dehydrogenase (G6PD) deficiency. The evidence base for the use of primaquine as a
      transmission blocker is limited by a lack of comparable clinical and
      parasitological endpoints between trials. In March 2012, a group of experts met
      in London to discuss the existing evidence on the ability of primaquine to block
      malaria transmission, to define the roadblocks to the use of primaquine in Africa
      and to develop a roadmap to enable its rapid, safe and effective deployment. The
      output of this meeting is a strategic plan to optimize trial design to reach
      desired goals efficiently. The roadmap includes suggestions for a series of phase
      1, 2, 3 and 4 studies to address specific hurdles to primaquine's deployment.
      These include ex-vivo studies on efficacy, primaquine pharmacokinetics and
      pharmacodynamics and dose escalation studies for safety in high-risk groups.
      Phase 3 community trials are proposed, along with Phase 4 studies to evaluate
      safety, particularly in pregnancy, through pharmacovigilance in areas where
      primaquine is already deployed. In parallel, efforts need to be made to address
      issues in drug supply and regulation, to map G6PD deficiency and to support the
      evaluation of alternative gametocytocidal compounds.

PMID- 23130963
TI  - Standard X-ray is inadequate for the identification of conductor cable
      externalization in Riata leads.

PMID- 23130962
TI  - Circadian rhythms in the efficacy of intravenous alteplase in patients with acute
      ischemic stroke and middle cerebral artery occlusion.
AB  - Circadian rhythm interactions of hemostatic factors can modify tissue plasminogen
      activator (tPA) effects. We assess the relationship of the time frame of
      intravenous tPA administration with the outcome of patients with acute ischemic
      stroke (AIS). We studied 135 consecutive patients with AIS and transcranial
      duplex documented middle cerebral artery (MCA) occlusion treated with intravenous
      tPA. Complete recanalization was defined as total improvement on thrombolysis in
      brain ischemia (TIBI) grades 2 h after tPA infusion. Clinical response was
      evaluated by the modified Rankin scale at 90 days. We determined plasminogen
      activator inhibitor-1 (PAI-1) levels in 33 patients with available plasma samples
      before treatment. Our results are follows: 92 (68.1%) patients were treated in
      the diurnal (9:00-21:00) and 43 (31.8%) in the nocturnal period (21:00-9:00).
      Complete recanalization was recorded in 52/135 (38.5%) patients. Both the rate of
      complete recanalization (45.6% vs. 23.2%; p = .01) and good clinical outcome
      (64.1% vs. 44.2%; p = .02) were significantly higher in the group of diurnal tPA
      administration compared with those treated in the nocturnal period. The adjusted
      odds ratio (OR) of diurnal tPA treatment for complete MCA recanalization was 2.37
      (95% confidence interval [CI], 1.02-5.52; p = .045). Diurnal tPA infusion
      significantly improved the overall distribution of scores on the modified Rankin
      scale, as compared with nocturnal treatment (OR, 2.07; 95% CI, 1.16-4.64 by
      ordinal regression analysis). Low PAI-1 levels were associated with complete
      recanalization but did not significantly differ between the two time frames. In
      conclusion, diurnal administration of tPA is associated with complete MCA
      recanalization and better functional outcome at 90 days in patients with AIS.

PMID- 23130964
TI  - Design and synthesis of dual modulators of soluble epoxide hydrolase and
      peroxisome proliferator-activated receptors.
AB  - Metabolic syndrome is a complex condition which often requires the use of
      multiple medications as a treatment. The resulting problems of polypharmacy are
      increase in side effects, drug-drug interactions, and its high economic cost.
      Development of multitarget compounds is a promising strategy to avoid the
      complications arising from administration of multiple drugs. Modulators of
      peroxisome proliferator-activated receptors (PPARs) are established agents in the
      treatment of dyslipidaemia, hyperglycaemia, and insulin resistance. Inhibitors of
      soluble epoxide hydrolase (sEH) are under evaluation for their use in
      cardiovascular diseases. In the present study, a series of dual sEH/PPAR
      modulators containing a pyrrole acidic headgroup and a urea pharmacophore were
      designed, synthesized, and evaluated in vitro using recombinant enzyme and cell
      based assays. Compounds with different activity profiles were obtained which
      could be used in the treatment of metabolic syndrome.

PMID- 23130965
TI  - Digestibility of fibre sources and molecular weight distribution of fibre
      fractions in ileal digesta of growing pigs.
AB  - Seven post-valve T-caecum cannulated growing pigs were used in a change-over
      experiment with four diets and four 14-day periods to evaluate the total tract
      apparent digestibility (TTAD) and the ileal apparent digestibility (IAD) of diets
      with inclusion of chicory forage (CFO), sugar beet pulp (SBP), wheat bran (WB)
      and grass meal (GM), as well as the TTAD of the mentioned fibre sources.
      Moreover, this experiment evaluated the molecular weight distribution of soluble
      non-starch polysaccharide (NSP) fractions in diet and ileal digesta from pigs fed
      the CFO and SBP diets. The experimental diets were balanced to have similar NSP
      content and compromised of one part of the basal diet and one part of the four
      fibre sources (CFO, SBP, WB and GM). In addition, all pigs were fed the basal
      diet during a 14-day period before and after the experimental periods. Diet
      affected the TTAD of all dietary components except glucose. The TTAD of organic
      matter (OM) was higher for Diet SBP than for Diets WB and CFO, showing both were
      higher than Diet GM. The TTAD of NSP was higher for Diet SBP than Diets WB and
      GM. The IAD of OM was higher in Diet SBP than in the other diets. The IAD of NSP
      was lower in Diet WB than in the other diets. The TTAD of OM and energy of CFO
      was 0.43 +/- 0.04 (standard error), which is similar to that reported for
      commonly used forage crops. The molecular weight distribution in ileal digesta
      showed different distributions between Diets CFO and SBP as well as between
      digesta from pigs fed these diets.

PMID- 23130966
TI  - Variations in chemical composition and in vitro and in situ ruminal degradation
      characteristics of dried distillers' grains with solubles from European ethanol
      plants.
AB  - The objective of this study was to characterise variations in the composition and
      nutritive value of dried distillers' grains with solubles (DDGS) for ruminants,
      and to estimate the undegradable crude protein (UDP) in DDGS. Thirteen samples
      originating from wheat, corn, barley and blends of different substrates were
      studied. The rumen degradation of crude protein (CP) was determined using the
      nylon bag technique. Samples were incubated for 0, 1, 2, 4, 8, 16, 32 and 72 h,
      and in situ degradation kinetics were determined. The UDP was estimated using a
      passage rate of 8%/h. In vitro gas production was measured to estimate the
      metabolisable energy (ME), net energy for lactation (NE(L)) and in vitro
      digestibility of organic matter (IVDOM). Chemical profiles varied among samples
      [in g/kg dry matter (DM) +/- standard deviation]; the values were 310 +/- 33 CP,
      86 +/- 37 ether extract, 89 +/- 18 crude fibre, 408 +/- 39 neutral detergent
      fibre, 151 +/- 39 acid detergent fibre and 62 +/- 31 acid detergent lignin, as
      well as in protein fractions according to the Cornell Net Carbohydrate and
      Protein System [in g/kg CP]; the values were for fractions A, 161 +/- 82; B1, 24
      +/- 11; B2, 404 +/- 105; B3, 242 +/- 61; and C, 170 +/- 87. The ME, NE(L) [MJ/kg
      DM] and IVDOM [%] also varied among samples: 12.1 +/- 0.59, 7.3 +/- 0.39 and 72.5
      +/- 4.30, respectively. The in situ rapidly degradable CP fraction (a) varied
      from 10.2% to 30.6%, and the potentially degradable fraction (b) averaged to
      66.8%. The UDP varied from 8.6% to 62.6% of CP. The present study suggests
      significant variations in composition and nutritive value among different sources
      of DDGS. The UDP could be predicted on the basis of analysed CP fractions, but
      the accuracy of UDP prediction improved upon the inclusion of neutral-detergent
      insoluble nitrogen, explaining 94% of the variation in the UDP values. We
      conclude that chemical protein fractions may be used to predict the UDP values of
      DDGS and that the variability in the protein fractions of DDGS should be
      considered when formulating diets for dairy cows.

PMID- 23130967
TI  - Equine pre-caecal and total tract digestibility of individual carbohydrate
      fractions and their effect on caecal pH response.
AB  - The working hypothesis was that a minor postprandial caecal pH decline would
      affect apparent total tract digestibility (ATTD) of the fibre fraction in horses
      and, hence, that soluble fibre would amplify fermentation and consequently
      increase ATTD of fibre. This study was a 4 * 4 Latin Square design with a
      sequence of 17 days adaptation to the ration followed by 8 sampling days. The
      feed rations consisted of only timothy hay (Group H), hay plus molassed sugar
      beet pulp combined with either whole oats (Group OB) or barley (Group BB) and hay
      plus loose chaff based concentrate (Group M). Four horses fitted with permanent
      caecal cannulas and collection harnesses were used. A pH electrode with logger
      was inserted through the cannula and caecal pH was recorded at 1 min intervals
      for 8 h. The mobile nylon bag technique was used to quantify pre-caecal loss
      (PCL) of individual feedstuffs. Fibre was analysed as dietary fibre (DF), non
      starch polysaccharides, soluble non-cellulosic polysaccharides (S-NCP), insoluble
      non-cellulosic polysaccharide (I-NCP) and neutral detergent fibre. The ATTD of
      the S-NCP fraction was above 0.8, which was 60% higher than for the I-NCP
      fraction. The PCL of starch were 0.98 (oats) and 0.75 (barley). The BB diet
      lowered (p < 0.001) postprandial caecal pH more than the other diets and a
      significant correlation was found between the lowest pH and ATTD of I-NCP (r = 
      0.66; p = 0.005). In conclusion, this study successfully measured the in vivo
      digestibility of individual fibre fractions and found that S-NCP was more
      digestible than the I-NCP, and that a single meal of unprocessed barley was
      sufficient to decrease caecal pH to such an extent that the fibre digestibility
      of the whole diet was negatively affected.

PMID- 23130969
TI  - An improved racemase/acylase biotransformation for the preparation of
      enantiomerically pure amino acids.
AB  - Using directed evolution, a variant N-acetyl amino acid racemase (NAAAR
      G291D/F323Y) has been developed with up to 6-fold higher activity than the wild
      type on a range of N-acetylated amino acids. The variant has been coupled with an
      enantiospecific acylase to give a preparative scale dynamic kinetic resolution
      which allows 98% conversion of N-acetyl-DL-allylglycine into D-allylglycine in 18
      h at high substrate concentrations (50 g L(-1)). This is the first example of
      NAAAR operating under conditions which would allow it to be successfully used on
      an industrial scale for the production of enantiomerically pure alpha-amino
      acids. X-ray crystal analysis of the improved NAAAR variant allowed a comparison
      with the wild-type enzyme. We postulate that a network of novel interactions that
      result from the introduction of the two side chains is the source of improved
      catalytic performance.

PMID- 23130970
TI  - Independent risk factors for infants who are small for gestational age by
      customised birthweight centiles in a multi-ethnic New Zealand population.
AB  - BACKGROUND: Infants born small for gestational age (SGA) by customised
      birthweight centiles are at increased risk of adverse outcomes compared with
      those SGA by population centiles. Risk factors for customised SGA have not
      previously been described in a general obstetric population. AIM: To determine
      independent risk factors for customised SGA in a multi-ethnic New Zealand
      population. METHODS: We performed a retrospective cohort analysis of
      prospectively recorded maternity data from 2006 to 2009 at National Women's
      Health, Auckland, New Zealand. After exclusion of infants with congenital
      anomalies and missing data, our final study population was 26,254 singleton
      pregnancies. Multivariable logistic regression analysis adjusted for ethnicity,
      body mass index, maternal age, parity, smoking status, social deprivation,
      hypertensive disease, antepartum haemorrhage (APH), diabetes and relevant pre
      existing medical conditions. RESULTS: Independent risk factors for SGA included
      obesity (adjusted odds ratio 1.24 [95% CI 1.11-1.39] relative to normal weight),
      maternal age >= 35 years (1.16 [1.05-1.30] relative to 20-29 years), nulliparity
      (1.13 [1.04-1.24] relative to parity 1), cigarette smoking (2.01 [1.79-2.27]),
      gestational hypertension (1.46 [1.21-1.75]), pre-eclampsia (2.94 [2.49-3.48]),
      chronic hypertension (1.68 [1.34-2.09]), placental abruption (2.57 [1.74-3.78])
      and APH of unknown origin (1.71 [1.45-2.00]). Gestational diabetes (0.80 [0.67
      0.96]) and type 1 diabetes (0.26 [0.11-0.64]) were associated with reduced risk.
      CONCLUSIONS: We report independent pregnancy risk factors for customised SGA in a
      general obstetric population. In contrast to population SGA, obesity is
      associated with increased risk. Our findings may help identify pregnancies that
      require increased fetal growth surveillance.

PMID- 23130971
TI  - Impacts of geochemical reactions on geologic carbon sequestration.

PMID- 23130972
TI  - People with aphasia: capacity to consent, research participation and intervention
      inequalities.
AB  - Of 14 randomized controlled trials included in the recent Cochrane review of the
      evidence relating to information provision after stroke, only one included people
      with aphasia with the remainder either excluding this patient sub-group (10/14
      trials) or failing to report any exclusion criteria. A third of people that
      experience a stroke will also experience aphasia, affecting their speaking,
      understanding, reading, and writing. The pervasive supposition that people with
      aphasia lack the capacity to make decisions for themselves is flawed and has the
      potential to lead to inequalities in care. We highlight the degree to which
      people with aphasia have been excluded from full participation in some areas of
      stroke research and the potential clinical consequences of their systematic
      exclusion. We emphasize the clinical and ethical need for the provision of more
      accessible research information and consent processes, illustrate the feasibility
      of adopting such an approach, and consider the broader benefits to stroke
      research of inclusive and accessible research approaches.

PMID- 23130973
TI  - An intramedullary cervical cord lesion in a 12-year-old girl.

PMID- 23130974
TI  - Implantable cardioverter defibrillators in patients with valvular cardiomyopathy.
AB  - BACKGROUND: Implantable cardioverter-defibrillators (ICDs) are beneficial for
      preventing sudden cardiac death (SCD) in patients with previous SCD or left
      ventricular dysfunction. OBJECTIVE: The objective was to investigate the outcomes
      of ICD implantation in patients who have surgery for valvular cardiomyopathy
      (VCM). METHODS: We identified patients with VCM who had ICD implantation after
      valve surgery. Age- and sex-matched patients who received an ICD for ischemic
      cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) served as controls.
      Patients with VCM who had valve surgery but did not receive an ICD served as an
      additional control group. We compared mortality and appropriate ICD discharges
      between the study group and control groups. RESULTS: Mean (SD) age (31 patients
      with VCM with ICD, 30 with ICM, 26 with DCM, and 62 patients with VCM without
      ICD) was 60 (15) years, 73% were men. Ejection fraction at ICD implantation was
      34%, 26%, and 23% for the VCM with ICD, ICM, and DCM groups, respectively (P =
      0.03). After a median follow-up of 4.1 years, survival was not significantly
      different among ICD groups (P = 0.06). The annual appropriate shock rate was 5%,
      10%, and 4% for the VCM with ICD, ICM, and DCM groups, respectively (P = 0.71).
      Compared to VCM without ICD, patients with VCM and ICD had comparable survival (P
      = 0.82) despite a reduced LVEF following valve surgery. CONCLUSION: Patients with
      VCM who undergo ICD implantation for SCD prevention have similar appropriate ICD
      discharge rates and mortality as do those with ICM and DCM. These data are
      hypothesis generating and deserve confirmation with large-scale prospective
      studies.

PMID- 23130975
TI  - Sick leave during pregnancy: a longitudinal study of rates and risk factors in a
      Norwegian population.
AB  - OBJECTIVE: To describe the prevalence of, reasons given for, and factors
      associated with sick leave during pregnancy. DESIGN: Longitudinal, population
      based descriptive study. SETTING: Akershus University Hospital, Norway.
      POPULATION: All women scheduled to give birth at the hospital (November 2008 to
      April 2010). METHODS: Consenting women were handed a questionnaire at the routine
      ultrasound check at 17 weeks of gestation. Women returning this questionnaire
      received a second questionnaire at 32 weeks of gestation. Multiple logistic
      regression analyses were performed to examine associations with somatic,
      psychiatric and social factors. MAIN OUTCOME MEASURES: Rates and duration of sick
      leave. RESULTS: By 32 weeks of gestation, 63.2% of the 2918 women included were
      on sick leave, and 75.3% had been on sick leave at some point during their
      pregnancy. Pelvic girdle pain and fatigue/sleep problems were the main reasons
      given for sick leave. Being on sick leave in all trimesters was strongly
      associated with hyperemesis, exercising less than weekly, chronic pain before or
      during pregnancy, infertility treatment (all P < 0.001); younger maternal age,
      conflicts in the workplace (both P < 0.01); multiparity, previous depression,
      insomnia and lower education (all P < 0.05). Sick leave was associated with
      elective caesarean section and higher infant birthweight (P < 0.01). Adjustment
      of the work situation was associated with 1 week shorter duration of sick leave.
      CONCLUSIONS: Most women receive sick leave during pregnancy, but sick leave might
      not be caused by pregnancy alone. Previous medical and psychiatric history, work
      conditions and socio-economic factors need to be addressed to understand sick
      leave during pregnancy.

PMID- 23130976
TI  - The hidden and forgotten evidence.

PMID- 23130977
TI  - Steady-state of an enzymatic reaction is dependent on the density of reactant.
AB  - The post-translational modification of proteins is controlled by the relative
      activities of two opposing enzymes. For example, the extent of phosphorylation of
      tyrosine residues reflects the balance of a kinase and a phosphatase enzyme. The
      present article uses as a model system a self-assembled monolayer that presents a
      peptide that can be phosphorylated by Abl kinase and subsequently
      dephosphorylated by Lambda phosphatase. Treatment of monolayers with a reaction
      mixture containing both enzymes reveals that the steady-state level of peptide
      phosphorylation is dependent on the density of the peptide. Using identical
      reaction mixtures, surfaces that presented the substrate at high density led to a
      phosphorylated peptide at steady-state, whereas surfaces that presented the
      substrate at low density led to unphosphorylated peptide at steady-state. This
      dependence owes to an autocatalytic phosphorylation reaction that operates at
      high densities of substrate. This work provides an example of an interfacial
      reaction that has properties that have no analogue in the corresponding solution
      phase reaction. It also provides a model system that is relevant to understanding
      mechanisms that regulate signaling at the cellular membrane.

PMID- 23130978
TI  - Rheumatological manifestations occurring in patients with diabetes mellitus.
AB  - OBJECTIVES: In this review we focus on the evidence for an association between
      musculoskeletal (MSK) manifestations and diabetes mellitus (DM). METHOD: A
      systematic literature review was performed using the PubMed database for articles
      that have been published in the past 8 years (from January 2003 to August 2011)
      for keywords referring to MSK manifestations and DM. Where possible we have
      distinguished between manifestations that occur in type 1 as opposed to type 2
      DM. However, this was not easy because many reports do not make the distinction.
      RESULTS: MSK manifestations of DM are relatively common. The duration of DM is
      often linked to the onset of some MSK features. CONCLUSIONS: Patients with DM
      have been reported to have an increased prevalence of several MSK manifestations.
      It is important to be aware of MSK complications of DM. A better control of the
      glucose level may be useful.

PMID- 23130979
TI  - A broadband, background-free quarter-wave plate based on plasmonic metasurfaces.
AB  - We demonstrate optically thin quarter-wave plates built with metasurfaces that
      generate high-quality circularly polarized light over a broad wavelength range
      for arbitrary orientation of the incident linear polarization. The metasurface
      consists of an array of plasmonic antennas with spatially varying phase and
      polarization responses. Experimentally demonstrated quarter-wave plates generate
      light with a high degree of circular polarization (>0.97) from lambda = 5 to 12
      MUm, representing a major advance in performance compared to previously reported
      plasmonics-based wave plates.

PMID- 23130980
TI  - Short stature in primary school students belonging to a minority ethnic group of
      Yao in China.
AB  - BACKGROUND: There are limited data on growth and diet of Yao minority ethnic
      children in Guangdong, China. AIM: To examine the growth of a group of Yao
      minority ethnic children in relation to their diet. SUBJECTS AND METHODS:
      Anthropometric data on 301 Yao boys and 303 Yao girls aged 9-15 years studying at
      a boarding school in Liannan, Guangdong were collected. Food and nutrient intakes
      was assessed by a food weighing method in 30 students and total fat content in
      diet was measured by chemical analysis on duplicate meals. Results were compared
      to those of similar aged school children in Hong Kong. RESULTS: The Yao group
      were shorter than Hong Kong children. Regardless of various international and
      Hong Kong growth references applied, Yao children consistently showed lower
      prevalence of overweight and obesity and a higher rate of stunting and thinness
      compared to Hong Kong children. The Yao group consumed less energy and less
      protein, derived mainly from natural plant-based food with significantly more
      grains and vegetables. CONCLUSION: The relative short stature of Yao children
      compared with Han Chinese children in Hong Kong may be accounted for by genetics
      and differences in nutrient intakes.

PMID- 23130985
TI  - Infrared laser spectroscopy of mass-selected carbocations.
AB  - Small carbocations are of longstanding interest in mass spectrometry, organic
      chemistry and astrophysics, but there are few measurements of their spectroscopy
      in the gas phase. Of existing infrared measurements, few are available across the
      full range of IR frequencies. In new work described here, a pulsed-discharge
      supersonic-nozzle ion source produces higher densities of carbocations at low
      temperatures (20-100 K). Mass-selected photodissociation spectroscopy and the
      method of rare gas "tagging", together with new broadly tunable infrared OPO
      lasers, produce IR spectra for a variety of small carbocations including
      C(2)H(3)(+), C(2)H(5)(+), C(3)H(3)(+), C(3)H(5)(+), the tert-butyl cation,
      protonated benzene, and protonated naphthalene. Spectra in the frequency range
      600-4500 cm(-1) provide new IR data for these ions and evidence for the presence
      of coexisting isomeric structures (e.g., C(3)H(3)(+) is present as both
      cyclopropenyl and propargyl). Protonated naphthalene has bands at 6.2, 7.7, and
      8.6 MUm matching prominent features in the interstellar unassigned infrared (UIR)
      emission spectra.

PMID- 23130986
TI  - Dynamics of the gel to fluid phase transformation in unilamellar DPPC vesicles.
AB  - The dynamics of the gel to fluid phase transformation in 100 nm large unilamellar
      vesicles (LUV) of 1,2-dipalmitoyl(d62)-sn-glycero-3-phosphocholine (d62-DPPC),
      has been studied by laser-induced temperature-jump initiation coupled with time
      resolved infrared spectroscopy and by MD simulations. The infrared transients
      that characterize the temperature dependent phase transformation are complex,
      extending from the nanosecond to the millisecond time scales. An initial fast
      (submicrosecond) component can be modeled by partial melting of the gel domains,
      initiated at pre-existing defects at the edges of the faceted structure of the
      gel phase. Molecular dynamics simulations support the model of fast melting from
      edge defects. The extent of melting during the fast phase is limited by the area
      expansion on melting, which leads to a surface pressure that raises the effective
      melting temperature. Subsequent melting is observed to follow highly stretched
      exponential kinetics, consistent with collective relaxation of the surface
      pressure through a hierarchy of surface undulations with different relaxation
      times. The slowest step is water diffusion through the bilayer to allow the
      vesicle volume to grow along with its expanded surface area. The results
      demonstrate that the dominant relaxation in the gel to fluid phase transformation
      in response to a large T-jump perturbation (compared to the transition width) is
      fast (submicrosecond), which has important practical and fundamental
      consequences.

PMID- 23130987
TI  - Phylogenetic relationship of the Brazilian isolates of the rat lungworm
      Angiostrongylus cantonensis (Nematoda: Metastrongylidae) employing mitochondrial
      COI gene sequence data.
AB  - BACKGROUND: The rat lungworm Angiostrongylus cantonensis can cause eosinophilic
      meningoencephalitis in humans. This nematode's main definitive hosts are rodents
      and its intermediate hosts are snails. This parasite was first described in China
      and currently is dispersed across several Pacific islands, Asia, Australia,
      Africa, some Caribbean islands and most recently in the Americas. Here, we report
      the genetic variability among A. cantonensis isolates from different geographical
      locations in Brazil using mitochondrial cytochrome c oxidase subunit I (COI) gene
      sequences. METHODS: The isolates of A. cantonensis were obtained from distinct
      geographical locations of Brazil. Genomic DNAs were extracted, amplified by
      polymerase reaction, purified and sequenced. A partial sequence of COI gene was
      determined to assess their phylogenetic relationship. RESULTS: The sequences of
      A. cantonensis were monophyletic. We identified a distinct clade that included
      all isolates of A. cantonensis from Brazil and Asia based on eight distinct
      haplotypes (ac1, ac2, ac3, ac4, ac5, ac6, ac7 and ac8) from a previous study.
      Interestingly, the Brazilian haplotype ac5 is clustered with isolates from Japan,
      and the Brazilian haplotype ac8 from Rio de Janeiro, Sao Paulo, Para and
      Pernambuco states formed a distinct clade. There is a divergent Brazilian
      haplotype, which we named ac9, closely related to Chinese haplotype ac6 and
      Japanese haplotype ac7. CONCLUSION: The genetic variation observed among
      Brazilian isolates supports the hypothesis that the appearance of A. cantonensis
      in Brazil is likely a result of multiple introductions of parasite-carrying rats,
      transported on ships due to active commerce with Africa and Asia during the
      European colonization period. The rapid spread of the intermediate host, Achatina
      fulica, also seems to have contributed to the dispersion of this parasite and the
      infection of the definitive host in different Brazilian regions.

PMID- 23130988
TI  - The Diabetes Pearl: Diabetes biobanking in The Netherlands.
AB  - BACKGROUND: Type 2 diabetes is associated with considerable comorbidity and
      severe complications, which reduce quality of life of the patients and require
      high levels of healthcare. The Diabetes Pearl is a large cohort of patients
      diagnosed with type 2 diabetes, covering different geographical areas in the
      Netherlands. The aim of the study is to create a research infrastructure that
      will allow the study of risk factors, including biomarkers and genetic
      determinants for severe diabetes complications. METHODS/DESIGN: Baseline
      examinations began November 2009 and will continue through 2012. By the end of
      2012, it is expected that 7000 patients with type 2 diabetes will be included in
      the Diabetes Pearl cohort. To ensure quality of the data collected, standard
      operation procedures were developed and used in all 8 recruitment centers. From
      all patients who provide informed consent, the following information is
      collected: personal information, medication use, physical examination
      (antropometry, blood pressure, electrocardiography (ECG), retina photographs,
      ankle-brachial index, peripheral vibration perception), self-report questionnaire
      (socio-economic status, lifestyle, (family) history of disease, and psychosocial
      well-being), laboratory measurements (glucose, A1c, lipid profile, kidney
      function), biobank material (storage of urine and blood samples and isolated
      DNA). All gathered clinical data and biobank information is uploaded to a
      database for storage on a national level. Biobanks are maintained locally at all
      recruitment centers. DISCUSSION: The Diabetes Pearl is large-scale cohort of type
      2 diabetes patients in the Netherlands aiming to study risk factors, including
      biomarkers and genetic markers, for disease deterioration and the development of
      severe diabetes complications. As a result of the well-designed research design
      and the national coverage, the Diabetes Pearl data can be of great value to
      national and international researchers with an interest in diabetes related
      research.

PMID- 23130989
TI  - In vivo susceptibility to benznidazole of Trypanosoma cruzi strains from the
      western Brazilian Amazon.
AB  - OBJECTIVE: To assess the susceptibility of Trypanosoma cruzi strains from Amazon
      to benznidazole. METHODS: We studied 23 strains of T. cruzi obtained from humans
      in the acute phase of Chagas disease, triatomines and marsupials in the state of
      Amazonas and from chronic patients and triatomines in the state of Parana,
      Brazil. The strains were classified as TcI (6), TcII (4) and TcIV (13). For each
      strain, 20 Swiss mice were inoculated: 10 were treated orally with benznidazole
      100 mg/kg/day (TBZ group) for 20 consecutive days and 10 comprised the untreated
      control group (NT). Fresh blood examination, haemoculture (HC), PCR, and ELISA
      were used to monitor the cure. RESULTS: The overall cure rate was 60.5% (109/180
      mice) and varied widely among strains. The strains were classified as resistant,
      partially resistant or susceptible to benznidazole, irrespective of discrete
      typing units (DTUs), geographical origin or host. However, the TcI strains from
      Amazonas were significantly (P = 0.028) more sensitive to benznidazole than the
      TcI strains from Parana. The number of parasitological, molecular and serological
      parameters that were significantly reduced by benznidazole treatment also varied
      among the DTUs; the TBZ group of mice inoculated with TcIV strains showed more
      reductions (8/9) than those with TcI and TcII strains. CONCLUSIONS: Benznidazole
      resistance was observed among natural populations of the parasite in the Amazon,
      even in those never exposed to the drug.

PMID- 23130990
TI  - Signal-on architecture for electrochemical aptasensors based on multiple ion
      channels.
AB  - In this work, we described a signal-on architecture for electrochemical
      aptasensors that is applicable to a wide range of aptamers. Herein, we use
      thrombin as the model sensing target. The signal-on aptasensor is composed of
      multiple ion channels embedded within a polymeric membrane, with the antithrombin
      aptamers chemically modified onto the inner walls of each ion channel working as
      the sensing element. As the thrombin concentration increased, [Ru(NH(3))(6)](3+),
      which was electrostatically absorbed onto the negatively charged phosphate
      backbones of aptamers beforehand, was displaced and pushed into the ion channels
      from the inner walls, leading to an increase in the current of redox cations at
      the working electrode surface. Compared with the traditional two-electrode design
      using a single ion channel sensing system, our ion channel sensing system is
      applied multiple times within an ordinary three-electrode system, providing such
      advantages as a high signal-to-noise ratio and suitability for a wide variety of
      redox species. The results indicate that multiple ion channel sensing provides
      improvements of orders of magnitude in signal sensitivity. In particular, this
      signal-on architecture avoids the problems of limited signal gain and "false
      positives". Moreover, the proposed aptasensor is simple, highly selective,
      stable, and applicable to real samples.

PMID- 23130991
TI  - Anatomical predictors for acute and mid-term success of cryoballoon ablation of
      atrial fibrillation using the 28 mm balloon.
AB  - INTRODUCTION: Cryoballoon (CB) pulmonary vein isolation (CB-PVI) for the
      treatment of paroxysmal atrial fibrillation (AF) has been demonstrated to be safe
      and reliable. Preprocedural patient selection to address the high variability in
      pulmonary vein (PV) anatomy may improve the acute and chronic success of CB-PVI.
      The purpose of this study was to identify anatomical predictors for CB-PVI
      failure using the 28 mm balloon. METHODS AND RESULTS: We included 47 patients
      with paroxysmal AF undergoing CB-PVI with the 28 mm CB. Anatomical global left
      atrial and PV selective parameters were quantified from 3-dimensional
      reconstructed preprocedural computed tomography or magnetic resonance imaging
      data. The mean follow-up was 26 +/- 9 months (range: 12-32 months). Multivariate
      logistic regression analysis revealed that a continuous sharp left lateral ridge
      between the left PVs and the left lateral appendage (OR, 7.09; 95% CI, 1.17
      43.47) and a sharp carina between the left superior and left inferior PV (OR,
      5.99; 95% CI, 1.33-27.03) predict acute and mid-term failure. For the right
      inferior PVs, a non-perpendicular angle between the axis of the PV and the ostial
      plane (OR, 6.33; 95% CI, 1.20-33.33) and an early branching PV with change in the
      axis angle (OR, 7.41; 95% CI, 1.44-38.46) were predictors of acute and mid-term
      failure. CONCLUSION: Anatomical variables preventing maximal heat transfer from
      the tissue to the CB could be identified as predictors for CB-PVI failure with
      the 28 mm balloon. These findings may be a step toward a more tailored ablation
      strategy based on individual anatomical variations.

PMID- 23130993
TI  - Synthesis, characterization, and computational studies of cycloparaphenylene
      dimers.
AB  - Two novel arene-bridged cycloparaphenylene dimers (1 and 2) were prepared using a
      functionalized precursor, bromo-substituted macrocycle 7. The preferred
      conformations of these dimeric structures were evaluated computationally in the
      solid state, as well as in the gas and solution phases. In the solid state, the
      trans configuration of 1 is preferred by 34 kcal/mol due to the denser crystal
      packing structure that is achieved. In contrast, in the gas phase and in
      solution, the cis conformation is favored by 7 kcal/mol (dimer 1) and 10 kcal/mol
      (dimer 2), with a cis to trans activation barrier of 20 kcal/mol. The
      stabilization seen in the cis conformations is attributed to the increased van
      der Waals interactions between the two cycloparaphenylene rings. These
      calculations indicate that the cis conformation is accessible in solution, which
      is promising for future efforts toward the synthesis of short carbon nanotubes
      (CNTs) via cycloparaphenylene monomers. In addition, the optoelectronic
      properties of these dimeric cycloparaphenylenes were characterized both
      experimentally and computationally for the first time.

PMID- 23130992
TI  - Confirmation of the absolute configuration at C45 of amphidinol 3.
AB  - Amphidinol 3 (AM3), a membrane-active agent isolated from the dinoflagellate
      Amphidinium klebsii, consists of a long carbon chain containing 25 stereogenic
      centers. Although the absolute configuration of AM3 was determined by extensive
      NMR analysis and degradation of the natural product, the partial structure
      corresponding to the tetrahydropyran ring system was found to be antipodal to
      that of karlotoxin 2, a structurally related compound recently isolated from the
      dinoflagellate Karlodinium veneficum. By extensive degradation of the natural
      product and conversion of the resulting alcohol to an MTPA ester, the absolute
      configuration at C45 of AM3 was confirmed to be R, supporting the originally
      proposed structure. 

PMID- 23130994
TI  - Kinetics of zero valent iron nanoparticle oxidation in oxygenated water.
AB  - Zero valent iron (ZVI) nanoparticles are versatile in their ability to remove a
      wide variety of water contaminants, and ZVI-based bimetallic nanoparticles show
      increased reactivity above that of ZVI alone. ZVI nanoparticles degrade
      contaminants through the reactive species (e.g., OH*, H(2(g)), H(2)O(2)) that are
      produced during iron oxidation. Measurement and modeling of aqueous ZVI
      nanoparticle oxidation kinetics are therefore necessary to optimize nanoparticle
      design. Stabilized ZVI and iron-nickel nanoparticles of approximately 150 nm in
      diameter were synthesized through solution chemistry, and nanoparticle oxidation
      kinetics were determined via measured mass change using a quartz crystal
      microbalance (QCM). Under flowing aerated water, ZVI nanoparticles had an initial
      exponential growth behavior indicating surface-dominated oxidation controlled by
      migration of species (H(2)O and O(2)) to the surface. A region of logarithmic
      growth followed the exponential growth which, based on the Mott-Cabrera model of
      thin oxide film growth, suggests a reaction dominated by movement of species
      (e.g., iron cations and oxygen anions) through the oxide layer. The presence of
      ethanol or a nickel shell on the ZVI nanoparticles delayed the onset of iron
      oxidation and reduced the extent of oxidation. In oxygenated water, ZVI
      nanoparticles oxidized primarily to the iron oxide-hydroxide lepidocrocite.

PMID- 23130995
TI  - Skirting the pitfalls: a clear-cut nomenclature for H3K4 methyltransferases.
AB  - To unravel the system of epigenetic control of transcriptional regulation is a
      fascinating and important scientific pursuit. Surprisingly, recent successes in
      gene identification using high-throughput sequencing strategies showed that,
      despite their ubiquitous role in transcriptional control, dysfunction of
      chromatin-modifying enzymes can cause very specific human developmental
      phenotypes. An intriguing example is the identification of de novo dominant
      mutations in MLL2 as a cause of Kabuki syndrome, a well-known congenital syndrome
      that is associated with a very recognizable facial gestalt. However, the existing
      confusion in the nomenclature of the human and mouse MLL gene family impedes
      correct interpretation of scientific findings for these genes and their encoded
      proteins. This Review aims to point out this nomenclature pitfall, to explain its
      historical background, and to promote an unequivocal nomenclature system for
      chromatin-modifying enzymes as proposed by Allis et al. (2007).

PMID- 23130996
TI  - The association between obesity and colorectal adenoma: systematic review and
      meta-analysis.
AB  - OBJECTIVE: Obesity (body mass index [BMI] >=30) or overweight (25 <= BMI <=29.9)
      has been reported to be a risk factor for colorectal adenoma (CRA). However, this
      association remains controversial. The aim of this study was to determine the
      association between overweight or obesity and CRA. DESIGN: Systematic review and
      meta-analysis were conducted using English language studies from EMBASE and
      MEDLINE. Appropriate observational studies were selected from 1966 through
      September 2011. Adjusted odds ratios (ORs) were extracted from each study.
      RESULTS: One hundred and seventy full-text articles were reviewed after
      retrieving 1199 initial search results. Five studies in which BMI was treated as
      continuous variable, three studies in which BMI was dichotomized using a cutoff
      value of 25, three studies in which BMI was categorized into three groups using
      values of 22 and 25, and eight studies in which BMI was categorized into three
      groups using values of 25 and 30 were selected. Regarding risk for CRA, pooled OR
      [95% CI] of one increment increase in BMI was 1.02 [0.99-1.03] (random effects
      model [REM]), while that of BMI >= 25 was 1.27 [1.15-1.4] (Fixed effects model).
      Pooled ORs [95% CI] of BMI >= 22 and BMI >= 25 was 1.42 [0.69-2.9] [REM] and 1.81
      [0.36-9.1] [REM], respectively. Pooled ORs [95% CI] of BMI >= 25 and BMI >= 30
      was 1.16 [0.98-1.38] [REM] and 1.47 [1.18-1.83] [REM], respectively. CONCLUSION:
      Obesity and overweight are significant risk factors for CRA. However, there are
      no data showing linear relationship between increasing BMI and CRA.

PMID- 23130997
TI  - Further evidence for the influence of photoperiod at birth on chronotype in a
      sample of German adolescents.
AB  - Individuals differ in their circadian preferences (chronotype). There is evidence
      in the literature to support a season-of-birth effect on chronotype but the
      evidence is not convincing. In part, the relationship is obscured by a number of
      methodological differences between studies, including the measures used to define
      morningness, the way in which the seasons were categorized, and the sample size.
      This study adds to the literature in several ways. First, we adopt a new approach
      to categorizing the photoperiod rather than the calendar season; thus we prefer
      to use the term photoperiod at birth. Second, we used two measures of
      morningness. Third, we used a large and homogeneous German sample. The results
      show that adolescents (n = 2905) born during the increasing photoperiod (Feb-Apr)
      had a significantly later midpoint of sleep (MSFsc) than those born during the
      decreasing photoperiod (Aug-Oct). A similar pattern was found for the Composite
      Scale of Morningness (CSM). Furthermore, both measures of chronotype demonstrated
      a significant quadratic function over a 1-yr cycle. When looking at each of six
      consecutive years separately, the Composite Scale of Morningness suggests a
      cosine rhythm linked to increasing and decreasing photoperiods that becomes
      weaker in amplitude with increasing age. Despite the strengths in our study, the
      effect of photoperiod at birth on chronotype remains small. Future studies may
      require larger sample sizes, may need to explore how neonatal light exposure
      modulates chronotype, and may need to track how puberty and adolescent lifestyle
      habits mask the photoperiod effect.

PMID- 23130998
TI  - Quantum conductance of silicon-doped carbon wire nanojunctions.
AB  - Unknown quantum electronic conductance across nanojunctions made of silicon-doped
      carbon wires between carbon leads is investigated. This is done by an appropriate
      generalization of the phase field matching theory for the multi-scattering
      processes of electronic excitations at the nanojunction and the use of the tight
      binding method. Our calculations of the electronic band structures for carbon,
      silicon, and diatomic silicon carbide are matched with the available
      corresponding density functional theory results to optimize the required tight
      binding parameters. Silicon and carbon atoms are treated on the same footing by
      characterizing each with their corresponding orbitals. Several types of
      nanojunctions are analyzed to sample their behavior under different atomic
      configurations. We calculate for each nanojunction the individual contributions
      to the quantum conductance for the propagating sigma, Pi, and sigma*electron
      incidents from the carbon leads. The calculated results show a number of
      remarkable features, which include the influence of the ordered periodic
      configurations of silicon-carbon pairs and the suppression of quantum conductance
      due to minimum substitutional disorder and artificially organized symmetry on
      these nanojunctions. Our results also demonstrate that the phase field matching
      theory is an efficient tool to treat the quantum conductance of complex molecular
      nanojunctions.

PMID- 23131000
TI  - Fibrosis score consisting of four serum markers successfully predicts
      pathological fibrotic stages of chronic hepatitis B.
AB  - AIM: In order to evaluate and judge a fibrotic stage of patients with chronic
      hepatitis B, multivariate regression analysis was performed using multiple
      fibrosis markers. METHOD: A total of 227 patients from seven hepatology units and
      institutes were diagnosed by needle biopsy as having chronic liver disease caused
      by hepatitis B virus. Twenty-three variables and their natural logarithmic
      transformation were employed in the multivariate analysis. Multiple regression
      function was generated from data of 158 patients in one hospital, and validation
      was performed using the other data of 69 patients from six other hospitals.
      RESULTS: After stepwise variable selection, multivariate regression analysis
      finally obtained the following function: z = 1.40 * ln (type IV collagen 7S)
      (ng/mL) - 0.017 * (platelet count) (*1000(3) /mm(3) ) + 1.24 * ln (tissue
      inhibitor of matrix metalloproteinase-2) (ng/mL) + 1.19 * ln (alpha-2
      macroglobulin) (mg/dL) - 9.15. Median values of fibrosis scores of F1 (n = 73),
      F2 (n = 42), F3 (n = 31) and F4 stages (n = 12) were calculated as 0.95, 2.07,
      2.98 and 3.63, respectively. Multiple regression coefficient and coefficient of
      determination were 0.646 and 0.418, respectively. Validation with patient data
      from other institutions demonstrated good reproducibility of fibrosis score for
      hepatitis B (FSB), showing 1.33 in F1 (n = 27), 2.20 in F2 (n = 20), 3.11 in F3
      (n = 20) and 5.30 in F4 (n = 2), respectively. CONCLUSION: A concise multiple
      regression function using four laboratory parameters successfully predicted
      pathological fibrosis stage of patients with hepatitis B virus infection.

PMID- 23130999
TI  - mGOASVM: Multi-label protein subcellular localization based on gene ontology and
      support vector machines.
AB  - BACKGROUND: Although many computational methods have been developed to predict
      protein subcellular localization, most of the methods are limited to the
      prediction of single-location proteins. Multi-location proteins are either not
      considered or assumed not existing. However, proteins with multiple locations are
      particularly interesting because they may have special biological functions,
      which are essential to both basic research and drug discovery. RESULTS: This
      paper proposes an efficient multi-label predictor, namely mGOASVM, for predicting
      the subcellular localization of multi-location proteins. Given a protein, the
      accession numbers of its homologs are obtained via BLAST search. Then, the
      original accession number and the homologous accession numbers of the protein are
      used as keys to search against the Gene Ontology (GO) annotation database to
      obtain a set of GO terms. Given a set of training proteins, a set of T relevant
      GO terms is obtained by finding all of the GO terms in the GO annotation database
      that are relevant to the training proteins. These relevant GO terms then form the
      basis of a T-dimensional Euclidean space on which the GO vectors lie. A support
      vector machine (SVM) classifier with a new decision scheme is proposed to
      classify the multi-label GO vectors. The mGOASVM predictor has the following
      advantages: (1) it uses the frequency of occurrences of GO terms for feature
      representation; (2) it selects the relevant GO subspace which can substantially
      speed up the prediction without compromising performance; and (3) it adopts an
      efficient multi-label SVM classifier which significantly outperforms other
      predictors. Briefly, on two recently published virus and plant datasets, mGOASVM
      achieves an actual accuracy of 88.9% and 87.4%, respectively, which are
      significantly higher than those achieved by the state-of-the-art predictors such
      as iLoc-Virus (74.8%) and iLoc-Plant (68.1%). CONCLUSIONS: mGOASVM can
      efficiently predict the subcellular locations of multi-label proteins. The
      mGOASVM predictor is available online at
      http://bioinfo.eie.polyu.edu.hk/mGoaSvmServer/mGOASVM.html.

PMID- 23131001
TI  - Editorial comment from Dr Funahashi to alpha1D/A-adrenoceptor antagonist
      naftopidil for the male lower urinary tract symptoms associated with benign
      prostatic hyperplasia: efficacy of dose increase therapy.

PMID- 23131002
TI  - Swelling-induced optical anisotropy of thermoresponsive hydrogels based on poly(2
      (2-methoxyethoxy)ethyl methacrylate): deswelling kinetics probed by quantitative
      Mueller matrix polarimetry.
AB  - Thermodynamically favored polymer-water interactions below the lower critical
      solution temperature (LCST) caused swelling-induced optical anisotropy (linear
      retardance) of thermoresponsive hydrogels based on poly(2-(2-methoxyethoxy)ethyl
      methacrylate). This was exploited to study the macroscopic deswelling kinetics
      quantitatively by a generalized polarimetry analysis method, based on measurement
      of the Mueller matrix and its subsequent inverse analysis via the polar
      decomposition approach. The derived medium polarization parameters, namely,
      linear retardance (delta), diattenuation (d), and depolarization coefficient
      (Delta), of the hydrogels showed interesting differences between the gels
      prepared by conventional free radical polymerization (FRP) and reversible
      addition-fragmentation chain transfer polymerization (RAFT) and also between dry
      and swollen state. The effect of temperature, cross-linking density, and
      polymerization technique employed to synthesize hydrogel on deswelling kinetics
      was systematically studied via conventional gravimetry and corroborated further
      with the corresponding Mueller matrix derived quantitative polarimetry
      characteristics (delta, d, and Delta). The RAFT gels exhibited higher swelling
      ratio and swelling-induced optical anisotropy compared to FRP gels and also
      deswelled faster at 30  degrees C. On the contrary, at 45  degrees C, deswelling
      was significantly retarded for the RAFT gels due to formation of a skin layer,
      which was confirmed and quantified via the enhanced diattenuation and
      depolarization parameters.

PMID- 23131003
TI  - Combined effects of surface roughness and wetting characteristics on the moving
      contact line in microchannel flows.
AB  - The present study investigates moving contact lines in microfluidic confinements
      with rough topographies modeled with random generating functions. Using matched
      asymptotic expansion, the description of the whole contact line is obtained and
      the dynamic contact angle is extracted by extrapolating the bulk meniscus to the
      channel wall. Significant variations are observed in the contact angle because of
      the heterogeneities of the confining walls of the microfluidic channel. The
      effects of the surface wetting condition also play a crucial role in altering the
      description of the contact line bearing particular nontrivial interactions with
      the topological features of the solid boundaries. In an effort to assess the
      underlying consequences, two different surface wetting conditions are studied;
      namely, complete wetting substrate and partial wetting substrate. Our studies
      reveal that the consequent wetting characteristics are strongly influenced by
      action of intermolecular forces in presence of surface roughness. The effect of
      slip, correlation length, and roughness parameters on the dynamic contact angle
      have been also investigated.

PMID- 23131004
TI  - Double tachycardia after slow pathway ablation for atrioventricular nodal
      tachycardia: what is the mechanism?

PMID- 23131005
TI  - GAL promoter-driven heterologous gene expression in Saccharomyces cerevisiae
      Delta strain at anaerobic alcoholic fermentation.
AB  - The removal of Gal80 protein by gene disruption turned into efficient GAL
      promoter-driven heterologous gene expression under anaerobic alcoholic
      fermentation of Saccharomyces cerevisiae. Using lipase B from Candida antarctica
      as a reporter, the relative strength of GAL10 promoter (P(GAL10) ) in Deltagal80
      mutant that does not require galactose as an inducer was compared to those of
      ADH1, PDC1, and PGK promoters, which have been known to work well anaerobically
      in actively fermenting yeast cells under high glucose concentration. P(GAL10)  in
      the Deltagal80 mutant showed 0.8-fold (ADH1), fourfold (PDC1), and 50-fold (PGK)
      in promoter strength.

PMID- 23131006
TI  - Epididymis microlithiasis and semen abnormalities in young adult kidney
      transplant recipients.
AB  - Microlithiasis of the epididymis is a rare ultrasound finding in the general
      population, but the incidence of calcifications in various organs of patients
      with end-stage renal disease (ESRD) is extremely high. The aim of this study was
      to describe epididymal microlithiasis in 22 previously dialysed patients who
      received kidney transplantations at a median age of 19 years (range 9-30). The
      patients underwent scrotum ultrasonography, semen analysis and laboratory tests
      (renal function, sexual hormones, Ca, P and PTH) and were administered the
      International Index of Erectile Function questionnaire. Seventeen presented
      calcifications of the epididymis, two of whom had concomitant testicular
      calcifications; a further three patients had isolated testicular calcifications
      without epididymis involvement. It was not possible to investigate the fertility
      of all of the patients but 12 of the 13 whose semen was analysed showed
      abnormalities: five were azoospermic and seven oligospermic with various degrees
      of morphological anomalies. To the best of our knowledge, these are the first
      published data concerning the prevalence of epididymal calcifications in young
      dialysed patients undergoing renal transplantation. Epididymal microlithiasis and
      infertility were common findings and so performing a spermiogram and preserving
      semen before ESRD for future paternity may be good advice in this selected
      population.

PMID- 23131008
TI  - Apparent acute reversible right ventricular pacing-induced left ventricular
      dysfunction.
AB  - We report the case of a 70-year-old Caucasian male with a dual chamber (right
      atrium/right ventricle) pacemaker implanted for sinus node dysfunction and not
      pacemaker (PM) dependent who was found to have an apparent acute worsening of
      left ventricular (LV) function with right ventricular (RV) apical pacing caused
      by the mode switch to VVI pacing as battery depletion occurred. LV dysfunction
      resolved immediately with RV pacing turned off. To our knowledge, this is the
      first report of this phenomenon.

PMID- 23131007
TI  - Is belief larger than fact: expectations, optimism and reality for translational
      stem cell research.
AB  - BACKGROUND: Stem cell (SC) therapies hold remarkable promise for many diseases,
      but there is a significant gulf between public expectations and the reality of
      progress toward clinical application. Public expectations are fueled by
      stakeholder arguments for research and public funding, coupled with intense media
      coverage in an ethically charged arena. We examine media representations in light
      of the expanding global landscape of SC clinical trials, asking what patients may
      realistically expect by way of timelines for the therapeutic and curative
      potential of regenerative medicine? METHODS: We built 2 international datasets:
      (1) 3,404 clinical trials (CT) containing 'stem cell*' from ClinicalTrials.gov
      and the World Health Organization's International Clinical Trials Registry Search
      Portal; and (2) 13,249 newspaper articles on SC therapies using Factiva.com. We
      compared word frequencies between the CT descriptions and full-text newspaper
      articles for the number containing terms for SC type and diseases/conditions. We
      also developed inclusion and exclusion criteria to identify novel SC CTs, mainly
      regenerative medicine applications. RESULTS: Newspaper articles focused on human
      embryonic SCs and neurological conditions with significant coverage as well of
      cardiovascular disease and diabetes. In contrast, CTs used primarily
      hematopoietic SCs, with an increase in CTs using mesenchymal SCs since 2007. The
      latter dominated our novel classification for CTs, most of which are in phases I
      and II. From the perspective of the public, expecting therapies for neurological
      conditions, there is limited activity in what may be considered novel
      applications of SC therapies. CONCLUSIONS: Given the research, regulatory, and
      commercialization hurdles to the clinical translation of SC research, it seems
      likely that patients and political supporters will become disappointed and
      disillusioned. In this environment, proponents need to make a concerted effort to
      temper claims. Even though the field is highly promising, it lacks significant
      private investment and is largely reliant on public support, requiring a more
      honest acknowledgement of the expected therapeutic benefits and the timelines to
      achieving them.

PMID- 23131009
TI  - Role of electronic perturbation in stability and activity of Pt-based alloy
      nanocatalysts for oxygen reduction.
AB  - The design of electrocatalysts for polymer electrolyte membrane fuel cells must
      satsify two equally important fundamental principles: optimization of
      electrocatalytic activity and long-term stability in acid media (pH <1) at high
      potential (0.8 V). We report here a solution-based approach to the preparation of
      Pt-based alloy with early transition metals and realistic parameters for the
      stability and activity of Pt(3)M (M = Y, Zr, Ti, Ni, and Co) nanocatalysts for
      oxygen reduction reaction (ORR). The enhanced stability and activity of Pt-based
      alloy nanocatalysts in ORR and the relationship between electronic structure
      modification and stability were studied by experiment and DFT calculations.
      Stability correlates with the d-band fillings and the heat of alloy formation of
      Pt(3)M alloys, which in turn depends on the degree of the electronic perturbation
      due to alloying. This concept provides realistic parameters for rational catalyst
      design in Pt-based alloy systems.

PMID- 23131011
TI  - Assimilation of oil-derived elements by oysters due to the Deepwater Horizon Oil
      Spill.
AB  - During and after the Deepwater Horizon Oil Spill (DWHOS), oysters (Crassostrea
      virginica) were exposed to oil and susceptible to incidental consumption of
      surface and subsurface oil materials. We determined the contribution of oil
      materials from the DWHOS to diet of oysters by comparing carbon (C) and nitrogen
      (N) stable isotope ratios in oyster shell to ratios in suspended particulate
      matter (SPM) and in fresh and weathered oil. Average delta(13)C and delta(15)N
      values in oyster shell (-21 +/- 10/00 and 9-110/00, respectively) were consistent
      with consumption of naturally available SPM as opposed to values in oil (-27 +/-
      0.20/00, 1.6 +/- 0.40/00). Stable isotope ratios in oyster adductor muscle were
      similar to shell for delta(15)N but not delta(13)C, suggesting either a recent
      shift in diet composition or differential assimilation of C between tissue types.
      We found no evidence of assimilation of oil-derived C and N and, therefore, no
      evidence of an oyster-based conduit to higher trophic levels. Trace elements in
      shell were inconclusive to corroborate oil exposure. These findings are not an
      indication that oysters were not exposed to oil; rather they imply oysters either
      did not consume oil-derived materials or consumed too little to be detectable
      compared to natural diet.

PMID- 23131012
TI  - Theoretical study of the dynamics and kinetics of the O + CS -> CO + S chemical
      laser reaction, where CO shows a very high vibrational excitation.
AB  - The dynamics and kinetics of the O((3)P) + CS(X(1)Sigma(+)) -> CO(X(1)Sigma(+)) +
      S((3)P) chemical laser reaction was studied theoretically in detail for the first
      time, as a function of collision energy (0.0388-2.0 eV) and rovibrational
      excitation of CS. This was made using the quasi-classical trajectory (QCT) method
      and employing the best ab initio analytical ground potential energy surface
      (1(3)A' PES) available. A broad set of properties was determined, including
      scalar and vector properties, and the reaction mode. The behaviors observed and
      the considerable formation of OCS collision complexes were interpreted from some
      characteristics of the PES (early barrier, shallow minimum in the exit channel,
      and high exoergicity (mainly channeled into CO vibration; up to ~81% of the
      available energy)) and the kinematics. The QCT vibrational and rotational CO
      populations and the vector properties show a quite good agreement with
      experiments, but the QCT rate constants disagree. To better account for the
      kinetics, we performed CASPT2/aug-cc-pVTZ ab initio calculations on the
      stationary points along the minimum energy path of the ground and first excited
      (1(3)A'') PESs. The transition state theory, which can be satisfactorily applied
      here, leads to rate constants (100-2000 K) that are quite close to the measured
      ones, where comparison is possible (150-300 K). We expect that these results will
      encourage further theoretical and experimental developments.

PMID- 23131013
TI  - 1,4-Diamination of cyclic dienes via a (4 + 3) cycloaddition of diaza-allyl
      cationic intermediates.
AB  - Diaza-(4 + 3) cycloadditions of putative diaza-oxyallyl cationic intermediates
      and cyclic dienes are reported as a method for the 1,4-diamination of cyclic
      dienes. This reaction was entirely selective for diamination and provided
      cycloadducts in good to excellent yield.

PMID- 23131014
TI  - Unmasking Kabuki syndrome.
AB  - The identification of de novo dominant mutations in KMT2D (MLL2) as the main
      cause of Kabuki syndrome (KS) has shed new light on the pathogenesis of this well
      delineated condition consisting of a peculiar facial appearance, short stature,
      organ malformations and a varying degree of intellectual disability. Mutation
      screening studies have confirmed KMT2D as the major causative gene for KS and
      have at the same time provided evidence for its genetic heterogeneity. In this
      review, we aim to summarize the current clinical and molecular genetic knowledge
      on KS, provide genotype-phenotype correlations and propose a strategic clinical
      and molecular diagnostic approach for patients with suspected KS.

PMID- 23131015
TI  - Identification of gram-negative bacteria from critical control points of raw and
      pasteurized cow milk consumed at Gondar town and its suburbs, Ethiopia.
AB  - BACKGROUND: Milk is highly prone to contamination and can serve as an efficient
      vehicle for human transmission of foodborne pathogens, especially gram-negative
      bacteria, as these are widely distributed in the environment. METHODS: This cross
      sectional study of gram-negative staining bacterial contamination of milk meant
      for human consumption was carried out from October 2010 to May 2011 in Gondar
      town, Ethiopia. Milk samples were collected from critical control points, from
      production to consumption, that were hypothesized to be a source of potential
      contamination. Milk sampling points included smallholder's milk producers, dairy
      co-operatives, a milk processing plant, and supermarkets. The hygienic procedures
      applied during milking, milk collection, transportation, pasteurization, and
      postpasteurization storage conditions at these specified critical control points
      were evaluated. Standard bacteriological cultivation and biochemical assays were
      used to isolate and identify bacterial pathogens in the milk samples. RESULTS:
      The results of the current study showed that conditions for contamination of raw
      milk at different critical points were due to less hygienic practices in pre
      milking udder preparation, sub-optimal hygiene of milk handlers, and poor
      sanitation practices associated with milking and storage equipments. Among all
      critical control points considered, transportation containers at milk collection
      centers and at processing plants were found to be the most heavily contaminated
      with gram-negative staining bacterial species. Overall, 54 different bacterial
      species were indentified, and Escherichia coli (29.6%), Pseudomonas aeruginosa
      (18.5%), and Klebsiella pneumoniae (16.7%), were the most commonly identified
      gram-negative staining bacterial pathogens. Of particular interest was that no
      gram-negative staining bacteria were isolated from pasteurized milk samples with
      varying shelf life. CONCLUSION: This study showed the presence of diverse
      pathogenic gram-negative staining bacterial species in raw milk that may be
      attributed to the sub-optimal sanitary conditions in the production and
      processing of milk in the Gondar town region. These results highlighted the need
      to maintain appropriate sanitary and hygienic measures at each critical point in
      order to safeguard consumers from foodborne pathogens. Further studies are
      recommended to identify additional critical control points, and to assess
      zoonotic risk factors to consumers.

PMID- 23131016
TI  - Yeast importin-beta is required for nuclear import of the Mig2 repressor.
AB  - BACKGROUND: Mig2 has been described as a transcriptional factor that in the
      absence of Mig1 protein is required for glucose repression of the SUC2 gene.
      Recently it has been reported that Mig2 has two different subcellular
      localizations. In high-glucose conditions it is a nuclear modulator of several
      Mig1-regulated genes, but in low-glucose most of the Mig2 protein accumulates in
      mitochondria. Thus, the Mig2 protein enters and leaves the nucleus in a glucose
      regulated manner. However, the mechanism by which Mig2 enters into the nucleus
      was unknown until now. RESULTS: Here, we report that the Mig2 protein is an
      import substrate of the carrier Kap95 (importin-beta). The Mig2 nuclear import
      mechanism bypasses the requirement for Kap60 (importin-alpha) as an adaptor
      protein, since Mig2 directly binds to Kap95 in the presence of Gsp1(GDP). We also
      show that the Mig2 nuclear import and the binding of Mig2 with Kap95 are not
      glucose-dependent processes and require a basic NLS motif, located between lysine
      32 and arginine-37. Mig2 interaction with Kap95 was assessed in vitro using
      purified proteins, demonstrating that importin-beta, together with the GTP
      binding protein Gsp1, is able to mediate efficient Mig2-Kap95 interaction in the
      absence of the importin-alpha (Kap60). It was also demonstrated, that the
      directionality of Mig2 transport is regulated by association with the small
      GTPase Gsp1 in the GDP- or GTP-bound forms, which promote cargo recognition and
      release, respectively. CONCLUSIONS: The Mig2 protein accumulates in the nucleus
      through a Kap95 and NLS-dependent nuclear import pathway, which is independent of
      importin-alpha in Saccharomyces cerevisiae.

PMID- 23131017
TI  - The categorisation of swimming start performance with reference to force
      generation on the main block and footrest components of the Omega OSB11 start
      blocks.
AB  - Work presented in this paper provides a methodology for categorising swimming
      start performance based on peak force production on the main block and footrest
      components of the Omega OSB11 starting block. A total of 46 elite British
      swimmers were tested, producing over 1000 start trials. Overwater cameras were
      synchronised to a specifically designed start block that allowed the measurement
      of force production via two sets of four, tri-axis, force transducers; one set in
      the main block and one in the footrest. Data were then analysed, segregating
      trials for gender. Each start was categorised, with respect to the peak force
      production in horizontal and vertical components, into one of nine categories.
      Three performance indicators, i.e. block time, take-off velocity and distance of
      entry, were used to assess whether differences in performance could be correlated
      with these categories. Results from these data suggest that swimmers generating
      higher than average peak forces were more likely to produce a better overall
      start performance than those who produced forces lower than the average, for this
      population of athletes.

PMID- 23131018
TI  - Improved immune status corresponds with long-term decline of quantitative serum
      hepatitis B surface antigen in HBV/HIV co-infected patients.
AB  - In HBV/HIV-co-infected individuals, the course of hepatitis B is aggravated,
      leading to higher morbidity and mortality rates. Increasing evidence suggests an
      important role for hepatitis B surface antigen (HBsAg) quantification in
      monitoring treatment efficacy in HBV monoinfection. However, data concerning any
      HBsAg decline during treatment of HBV/HIV coinfection are limited. Fifty-one
      HBV/HIV-co-infected patients were retrospectively followed for a mean of 43
      months (median 2 years, interquartile range 2 years). Baseline and on-treatment
      parameters were associated with longitudinal HBsAg levels. At baseline, serum
      HBsAg levels were comparable between patients on antiretroviral therapy (ART;
      n=43) and patients without (n=8). Longitudinally, HBsAg decreased in ART patients
      (-0.20+/-0.09 log(10) IU/mL/y), but slightly increased in subjects without
      therapy (0.22+/-0.26 log(10) IU/mL/y; p<0.001). In 58% of the ART subjects an
      HBsAg decline >10% was seen during the initial 24 mo. They showed higher baseline
      CD4 counts (401+/-42 versus 265+/-50 cells/MUL, p=0.03), and had significantly
      higher CD4 counts at the last follow-up compared to patients without a decline
      (506+/-39 versus 310+/-51 cells/MUL, p=0.01). A significant correlation was found
      between HBsAg decline from baseline to the last follow-up and the absolute
      increase of CD4 cells (r=0.44, p=0.003), as well the last CD4 count (r=0.41,
      p=0.006). This association was strongest in patients with complete suppression of
      HBV-DNA and HIV-RNA at the last follow-up visit. The highest HBsAg decline (
      1.63+/-0.32 versus -0.43+/-0.24 log(10) IU/mL, p=0.001), and yearly HBsAg decline
      (-0.47+/-0.13 versus -0.19+/-0.12 log(10) IU/mL, p=0.03), were found in patients
      with CD4 increases >100 cells/MUL at the last follow-up (n=21, 49%). Four cases
      of HBsAg loss were observed (8%). HBsAg declines steadily in >50% of HBV/HIV
      patients on ART. Long-term follow-up of HBV/HIV-co-infected patients is needed to
      identify distinct HBsAg patterns. Increasing CD4 counts indicating the
      restoration of immune competence in HBV/HIV-co-infected patients is associated
      with a stronger HBsAg decline.

PMID- 23131019
TI  - Physical activity and sex modulate obesity risk linked to 3111T/C gene variant of
      the CLOCK gene in an elderly population: the SUN Project.
AB  - Genetic factors may interact with physical activity levels to modify obesity
      risk. Our aim was to explore the influence of rs1801260 single-nucleotide
      polymorphism (SNP) (3111T/C) of CLOCK gene on obesity risk, and to examine its
      potential interaction with lifestyle factors in an elderly population within the
      SUN ("Seguimiento Universidad de Navarra") Project. Subjects (n = 903, aged 69 +/
      6 yrs) were recruited from the SUN Project. DNA was obtained from saliva,
      whereas lifestyle and dietary data were collected by validated self-report
      questionnaires. Genotype was assessed by reverse transcriptase-polymerase chain
      reaction (RT-PCR) plus allele discrimination. A significant interaction was
      observed between the 3111T/C SNP of CLOCK gene and sex for overweight/obesity
      risk (p for sex * CLOCK interaction <.001). Our results showed that women
      carrying the C allele of CLOCK gene had a marginally significant lower risk of
      overweight/obesity compared with noncarrier-TT-subjects (odds ratio [OR]: .61,
      95% confidence interval [CI]: .36-1.04; p = .069). Moreover, this association of
      the C allele with a decreased overweight/obesity risk might be enhanced in those
      women with a high physical activity level. Women practicing more than 16.8
      metabolic equivalent tasks (hours per week) had a significantly lower
      overweight/obesity risk (OR: .36, 95% CI: .17-.79; p = .011). Furthermore, a
      significant interaction between the 3111T/C gene variant and physical activity
      (PA) for overweight/obesity risk was observed but only in women (p for PA * CLOCK
      interaction <.050). In conclusion, it appears that physical activity levels may
      act by modifying the association of the 3111T/C SNP (rs1801260) of the CLOCK gene
      with overweight/obesity risk in elderly women in the SUN Project.

PMID- 23131020
TI  - USRCAT: real-time ultrafast shape recognition with pharmacophoric constraints.
AB  - BACKGROUND: Ligand-based virtual screening using molecular shape is an important
      tool for researchers who wish to find novel chemical scaffolds in compound
      libraries. The Ultrafast Shape Recognition (USR) algorithm is capable of
      screening millions of compounds and is therefore suitable for usage in a web
      service. The algorithm however is agnostic of atom types and cannot discriminate
      compounds with similar shape but distinct pharmacophoric features. To solve this
      problem, an extension of USR called USRCAT, has been developed that includes
      pharmacophoric information whilst retaining the performance benefits of the
      original method. RESULTS: The USRCAT extension is shown to outperform the
      traditional USR method in a retrospective virtual screening benchmark. Also, a
      relational database implementation is described that is capable of screening a
      million conformers in milliseconds and allows the inclusion of complex query
      parameters. CONCLUSIONS: USRCAT provides a solution to the lack of atom type
      information in the USR algorithm. Researchers, particularly those with only
      limited resources, who wish to use ligand-based virtual screening in order to
      discover new hits, will benefit the most. Online chemical databases that offer a
      shape-based similarity method might also find advantage in using USRCAT due to
      its accuracy and performance. The source code is freely available and can easily
      be modified to fit specific needs.

PMID- 23131022
TI  - H2 S inhibits the activation of hepatic stellate cells and downregulates the
      expression of urotensin II.
AB  - AIM: H2 S, a newly discovered signaling gasotransmitter, has been found involved
      in the pathogenesis of portal hypertension through the H2 S/CSE system. Studies
      also showed that urotensin II (UII), a recently discovered most potent
      vasoconstrictor, played an important role in cirrhotic portal hypertension.
      Therefore, studies were conducted to explore the relationship between H2 S and
      UII in cirrhosis. METHODS: In the present study, the changes in the expression
      levels of cystathionine-gamma-lyase (CSE), UII, urotensin II receptor (UT),
      collagen I, collagen III, tissue inhibitor of metalloproteinase-1 (TIMP-1) and
      alpha-smooth muscle actin (alpha-SMA) were determined by fluorescence
      quantitative polymerase chain reaction after exposure of hepatic stellate cells
      to H2 S. The influence of H2 S on UII was examined by western blotting, and the
      relationship between H2 S and UII was further confirmed by detection of cell
      proliferation and apoptosis. RESULTS: Studies have shown that increase in H2 S
      concentration could reduce the expression of UII, UT, collagen I, collagen III,
      TIMP-1 and alpha-SMA without involvement of CSE. Moreover, the results of western
      blotting further proved that H2 S inhibited the expression of UII. The
      examination of cell proliferation by 5-ethynyl-2'-deoxyuridine assay suggests
      that H2 S significantly inhibited the proliferation of LX-2 cells and the
      proliferation-promoting effect of UII. Similarly, the examination of cell
      apoptosis revealed that H2 S could promote LX-2 cell apoptosis and inhibit the
      apoptosis-inhibiting effect of UII. CONCLUSION: H2 S suppresses fibrosis by
      inhibiting the activation of hepatic stellate cells and reducing the expression
      of UII.

PMID- 23131021
TI  - Coupling the Torpedo microplate-receptor binding assay with mass spectrometry to
      detect cyclic imine neurotoxins.
AB  - Cyclic imine neurotoxins constitute an emergent family of neurotoxins of
      dinoflagellate origin that are potent antagonists of nicotinic acetylcholine
      receptors. We developed a target-directed functional method based on the
      mechanism of action of competitive agonists/antagonists of nicotinic
      acetylcholine receptors for the detection of marine cyclic imine neurotoxins. The
      key step for method development was the immobilization of Torpedo electrocyte
      membranes rich in nicotinic acetylcholine receptors on the surface of microplate
      wells and the use of biotinylated-alpha-bungarotoxin as tracer. Cyclic imine
      neurotoxins competitively inhibit biotinylated-alpha-bungarotoxin binding to
      Torpedo-nicotinic acetylcholine receptors in a concentration-dependent manner.
      The microplate-receptor binding assay allowed rapid detection of nanomolar
      concentrations of cyclic imine neurotoxins directly in shellfish samples.
      Although highly sensitive and specific for the detection of neurotoxins targeting
      nicotinic acetylcholine receptors as a class, the receptor binding assay cannot
      identify a given analyte. To address the low selectivity of the microplate
      receptor binding assay, the cyclic imine neurotoxins tightly bound to the coated
      Torpedo nicotinic receptor were eluted with methanol, and the chemical nature of
      the eluted ligands was identified by mass spectrometry. The immobilization of
      Torpedo electrocyte membranes on the surface of microplate wells proved to be a
      high-throughput format for the survey of neurotoxins targeting nicotinic
      acetylcholine receptors directly in shellfish matrixes with high sensitivity and
      reproducibility.

PMID- 23131023
TI  - Gene therapy for lower urinary tract dysfunction.
AB  - Lower urinary tract dysfunction is caused by functional and pathophysiological
      alterations of the peripheral organs, including the urothelium and detrusor
      smooth muscle, as well as peripheral and central nervous systems. Recent research
      in this field has increased our understanding of the mechanisms of lower urinary
      tract dysfunction, and new drugs have been developed, leading to increased
      treatment options and changing medical care for lower urinary tract symptoms.
      Nevertheless, clinicians still often experience refractory and treatment
      resistant cases against conventional therapeutic modalities. For such cases, gene
      therapy targeting for the lower urinary tract and its afferent pathway is
      anticipated to offer a new therapeutic approach. Therefore, in this article, we
      review the possibility and current status of gene therapy for lower urinary tract
      dysfunction.

PMID- 23131025
TI  - Ultrasound-guided venous access for pacemakers and defibrillators.
AB  - INTRODUCTION: Ultrasound guidance is widely recommended to reduce the risk of
      complications during central venous catheter placement. However, ultrasound
      guidance is not commonly utilized for implanting leads for cardiac rhythm
      management devices. METHODS AND RESULTS: We describe our technique of ultrasound
      guided pacemaker implantation, including a novel pull-through technique that
      allows percutaneous guidewire insertion prior to the first incision. We review
      the literature and recent advances in ultrasound imaging technology that may
      facilitate the adoption of ultrasound guidance. CONCLUSIONS: Ultrasound guidance
      provides a safe and rapid technique for extrathoracic subclavian or axillary
      venous lead placement.

PMID- 23131026
TI  - Quantum dots conjugated with Fe3O4-filled carbon nanotubes for cancer-targeted
      imaging and magnetically guided drug delivery.
AB  - A novel and specific nanoplatform for in vitro simultaneous cancer-targeted
      optical imaging and magnetically guided drug delivery is developed by conjugating
      CdTe quantum dots with Fe(3)O(4)-filled carbon nanotubes (CNTs) for the first
      time. Fe(3)O(4) is filled into the interior of the CNTs, which facilitates
      magnetically guided delivery and improves the synergetic targeting efficiency. In
      comparison with that immobilized on the external surface of CNTs, the magnetite
      nanocrystals inside the CNTs protect it from agglomeration, enhance its chemical
      stability, and improve the drug loading capacity. It also avoids magnetic
      nanocrystals-induced quenching of fluorescence of the quantum dots. The SiO(2)
      coated quantum dots (HQDs) attached on the surface of CNTs exhibit favorable
      fluorescence as the hybrid SiO(2) shells on the QDs surface prevent its
      fluorescence quenching caused by the CNTs. In addition, the hybrid SiO(2) shells
      also mitigate the toxicity of the CdTe QDs. By coating transferrin on the surface
      of the herein modified CNTs, it provides a dual-targeted drug delivery system to
      transport the doxorubicin hydrochloride (DOX) into Hela cells by means of an
      external magnetic field. The nanocarrier based on the multifunctional
      nanoplatform exhibits an excellent drug loading capability of ca. 110%, in
      addition to cancer-targeted optical imaging as well as magnetically guided drug
      delivery.

PMID- 23131027
TI  - Influence of a flavan-3-ol substituent on the affinity of anthocyanins (pigments)
      toward vinylcatechin dimers and proanthocyanidins (copigments).
AB  - The aim of this study is to investigate interactions possibly taking place in red
      wine between three flavanols (copigments, CP), i.e., two epimeric vinylcatechin
      dimers (CP1 and CP2) and catechin dimer B3 (CP3), and a specific pigment
      resulting from the condensation between the main grape anthocyanin malvidin 3-O
      glucoside (oenin) and catechin, catechin-(4->8)-oenin. By comparison with our
      previous work on oenin itself, the influence of the catechin moiety of the
      anthocyanin in the binding is established. The thermodynamic parameters show that
      both vinylcatechin dimers exhibit a higher affinity for catechin-(4->8)-oenin, in
      comparison with proanthocyanidin B3, as previously observed with oenin. However,
      the corresponding binding constants are weaker, probably due to steric hindrance
      in the anthocyanin brought by the flavanol nucleus. Consequently, catechin-(4->8)
      oenin should be much less stabilized by copigmentation in hydroalcoholic solution
      than oenin. Quantum mechanics and molecular dynamics simulations are also
      performed to interpret the binding data, to specify the relative arrangement of
      the pigment and copigment molecules within the complexes, and to interpret their
      absorption properties in the visible range.

PMID- 23131028
TI  - Cobalt-catalyzed asymmetric 1,6-addition of (triisopropylsilyl)-acetylene to
      alpha,beta,gamma,delta-unsaturated carbonyl compounds.
AB  - Asymmetric addition of (triisopropylsilyl)acetylene to alpha,beta,gamma,delta
      unsaturated carbonyl compounds took place in the presence of a cobalt/Duphos
      catalyst to give the 1,6-addition products in high yields with high regio- and
      enantioselectivity.

PMID- 23131029
TI  - Fungal infections associated with contaminated methylprednisolone in Tennessee.
AB  - BACKGROUND: We investigated an outbreak of fungal infections of the central
      nervous system that occurred among patients who received epidural or paraspinal
      glucocorticoid injections of preservative-free methylprednisolone acetate
      prepared by a single compounding pharmacy. METHODS: Case patients were defined as
      patients with fungal meningitis, posterior circulation stroke, spinal
      osteomyelitis, or epidural abscess that developed after epidural or paraspinal
      glucocorticoid injections. Clinical and procedure data were abstracted. A cohort
      analysis was performed. RESULTS: The median age of the 66 case patients was 69
      years (range, 23 to 91). The median time from the last epidural glucocorticoid
      injection to symptom onset was 18 days (range, 0 to 56). Patients presented with
      meningitis alone (73%), the cauda equina syndrome or focal infection (15%), or
      posterior circulation stroke with or without meningitis (12%). Symptoms and signs
      included headache (in 73% of the patients), new or worsening back pain (in 50%),
      neurologic symptoms (in 48%), nausea (in 39%), and stiff neck (in 29%). The
      median cerebrospinal fluid white-cell count on the first lumbar puncture among
      patients who presented with meningitis, with or without stroke or focal
      infection, was 648 per cubic millimeter (range, 6 to 10,140), with 78%
      granulocytes (range, 0 to 97); the protein level was 114 mg per deciliter (range,
      29 to 440); and the glucose concentration was 44 mg per deciliter (range, 12 to
      121) (2.5 mmol per liter [range, 0.7 to 6.7]). A total of 22 patients had
      laboratory confirmation of Exserohilum rostratum infection (21 patients) or
      Aspergillus fumigatus infection (1 patient). The risk of infection increased with
      exposure to lot 06292012@26, older vials, higher doses, multiple procedures, and
      translaminar approach to epidural glucocorticoid injection. Voriconazole was used
      to treat 61 patients (92%); 35 patients (53%) were also treated with liposomal
      amphotericin B. Eight patients (12%) died, seven of whom had stroke. CONCLUSIONS:
      We describe an outbreak of fungal meningitis after epidural or paraspinal
      glucocorticoid injection with methylprednisolone from a single compounding
      pharmacy. Rapid recognition of illness and prompt initiation of therapy are
      important to prevent complications. (Funded by the Tennessee Department of Health
      and the Centers for Disease Control and Prevention.).

PMID- 23131030
TI  - The use of complementary and alternative medicine for patients with traumatic
      brain injury in Taiwan.
AB  - BACKGROUND: The use of complementary and alternative medicine (CAM) continues to
      increase in Taiwan. This study examined the use of CAM and beliefs about CAM as
      expressed by patients with traumatic brain injury (TBI) in Taiwan. METHODS: TBI
      patients and their accompanying relatives were interviewed by using a structured
      questionnaire at an outpatient clinic in a medical center in northern Taiwan.
      RESULTS: A total of 101 patients with TBI participated in the study. Sixty-four
      (63%) patients had used at least one form of CAM after sustaining TBI. CAM users
      had used an average of 2.72 forms of CAM after sustaining TBI. The most
      frequently used CAM category was traditional Chinese medicine (37; 57.8%),
      followed by folk and religious therapies (30; 46.9%), and dietary supplements
      (30; 46.9%). The majority of the patients (45; 70.3%) did not report CAM use
      because they felt it was unnecessary to do so. Patients who used CAM had a
      significantly stronger positive belief in CAM than those who did not (t = -2.72;
      P = .008). After using CAM, most of the patients (54; 85%) perceived moderate
      satisfaction (2.89 +/- 0.44), according to a 4-point Likert scale. CONCLUSION:
      Although the use of CAM is common for TBI patients receiving conventional medical
      health care in Taiwan, most patients did not inform health care personnel about
      their CAM use. TBI patients perceive combined use of CAM and conventional
      medicine as beneficial for their overall health.

PMID- 23131033
TI  - Early recurrences are not always benign after catheter ablation of atrial
      fibrillation:do we need to reassess the need for a blanking period?

PMID- 23131031
TI  - Correlates between host and viral transcriptional program associated with
      different oncolytic vaccinia virus isolates.
AB  - Vaccinia virus (VACV) has emerged as an attractive tool in oncolytic virotherapy.
      VACV replication efficiency plays a crucial role in the therapeutic outcome.
      However, little is known about the influence of host factors on viral replication
      efficiency and permissiveness of a host cell line to infection and oncolysis. In
      this study, replication of the attenuated VACV GLV-1h68 strain and three wild
      type VACV isolates was determined in two autologous human melanoma cell lines
      (888-MEL and 1936-MEL). Host gene expression and viral gene expression in
      infected cells were evaluated via respective expression array platforms.
      Microarray analyses followed by sequential statistical approaches characterized
      human genes that change specifically due to virus infection. Viral gene
      transcription correlated with viral replication in a time-dependent manner. A set
      of human genes revealed strong correlations with the respective viral gene
      expression. Finally we identified a set of human genes with possible predictive
      value for viral replication in an independent dataset. The results demonstrate a
      probable correlation between viral replication, early gene expression, and the
      respective host response, and thus a possible involvement of human host factors
      in viral early replication. The characterization of human target genes that
      influence viral replication could help answer the question of host cell
      permissiveness to oncolytic virotherapy and provide important information for the
      development of novel recombinant vaccinia viruses with improved features to
      enhance replication rate and hence trigger therapeutic outcome.

PMID- 23131034
TI  - Circadian variation in patient characteristics and outcomes in ST-segment
      elevation myocardial infarction.
AB  - A morning peak in ST-segment elevation myocardial infarction (STEMI) has been
      described. The authors explored the relationship between variation of symptom
      onset, patient characteristics, and outcomes in two worldwide fibrinolytic
      trials. A total of 35 492 patients with STEMI were grouped into 8-h intervals by
      time of symptom onset: early (06:00 to 13:59 h), late-day (14:00 to 21:59 h),
      overnight (22:00 to 05:59 h). The authors correlated timing with patient
      characteristics and outcomes (adjusted for thrombolysis in myocardial infarction
      [TIMI] risk score) first in InTIME II-TIMI 17 trial (N = 15 031), and confirmed
      in the ExTRACT-TIMI 25 trial (N = 20 461). Timing was similar in the derivation
      (early 49%, late-day 30%, and overnight 21%; p < .001) and validation set (48%,
      31%, and 21%, respectively; p < .001). Some patient characteristics consistently
      varied with time of symptom onset. Patients in the early cohort were older with
      poorer renal function. The late-day group had more smokers with higher initial
      heart rate and systolic blood pressure. Those with overnight symptom onset had
      higher rates of obesity, prior myocardial infarction, and treatment delays. Prior
      use of aspirin and beta-blockers was also highest in the overnight group.
      Relative to the early cohort, adjusted mortality was higher with late-day onset
      (derivation odds ratio [OR]: 1.19, p = .04; validation OR: 1.18, p = .01), but
      there was no excess in mortality overnight compared with early (derivation OR:
      .97, p = .72; validation OR: 1.01, p = .90). Composite endpoints followed similar
      patterns. This study indicates that circadian patterns in onset of STEMI continue
      to exist with patient characteristics differing by time of day. Despite a
      potential physiologic resistance to morning thrombolysis, outcomes were best in
      the early cohort, intermediate overnight, and worst with late-day symptom onset.
      Efforts to reduce smoking and improve control of blood pressure could reduce the
      number of patients with late-day onset of STEMI who experience the worst
      outcomes.

PMID- 23131032
TI  - Long-term expression and safety of administration of AAVrh.10hCLN2 to the brain
      of rats and nonhuman primates for the treatment of late infantile neuronal ceroid
      lipofuscinosis.
AB  - Late infantile neuronal ceroid lipofuscinosis (LINCL), a fatal, lysosomal storage
      disorder caused by mutations in the CLN2 gene, results in a deficiency of
      tripeptidyl-peptidase I (TPP-I) activity in neurons. Our prior studies showed
      that delivery of the human CLN2 cDNA directly to the CNS, using an adeno
      associated virus serotype 2 (AAV2) vector, is safe in children with LINCL. As a
      second-generation strategy, we have demonstrated that AAVrh.10hCLN2, a rhesus
      derived AAV vector, mediates wide distribution of TPP-I through the CNS in a
      murine model. This study tests the hypothesis that direct administration of
      AAVrh.10hCLN2 to the CNS of rats and nonhuman primates at doses scalable to
      humans has an acceptable safety profile and mediates significant CLN2 expression
      in the CNS. A dose of 10(11) genome copies (GC) was administered bilaterally to
      the striatum of Sprague Dawley rats with sacrifice at 7 and 90 days with no
      significant impact except for mild vector-related histopathological changes at
      the site of vector administration. A dose of 1.8*10(12) GC of AAVrh.10hCLN2 was
      administered to the CNS of 8 African green monkeys. The vector-treated monkeys
      did not differ from controls in any safety parameter except for mild to moderate
      white matter edema and inflammation localized to the administration sites of the
      vector. There were no clinical sequelae to these localized findings. TPP-I
      activity was >2 SD over background in 31.7+/-8.1% of brain at 90 days. These
      findings establish the dose and safety profile for human clinical studies for the
      treatment of LINCL with AAVrh.10hCLN2.

PMID- 23131035
TI  - Effect of JPEG compression on the diagnostic accuracy of periapical images;
      mistakes and misinterpretations.

PMID- 23131036
TI  - On-chip integrated mid-infrared GaAs/AlGaAs Mach-Zehnder interferometer.
AB  - We report the design, fabrication, and first functional verification of mid
      infrared (MIR; 3-12 MUm) Mach-Zehnder interferometers (MZIs). The developed MIR
      MZIs are entirely chip-integrated solid-state devices based on GaAs/AlGaAs
      technology waveguide fabricated via conventional optical lithography and reactive
      ion etching (RIE). Thus, fabricated MIR-MZIs were combined with a broadly tunable
      quantum cascade laser (tQCL) providing a wavelength coverage of 5.78-6.35 MUm.
      MIR-MZIs have been designed with a waveguide width of 5 MUm to ensure single mode
      behavior, avoiding optically undefined interference patterns. Several structures
      with different opening angles of the Y-junction were fabricated and tested for
      maximizing IR radiation throughput. This study demonstrates the feasibility of
      the very first chip-integrated mid-infrared Mach-Zehnder structures via
      interference patterns produced by minute amounts of water deposited at different
      positions of the MIR-MZI structure.

PMID- 23131037
TI  - CD8+ and CD4+ cytotoxic T cell escape mutations precede breakthrough SIVmac239
      viremia in an elite controller.
AB  - BACKGROUND: Virus-specific T cells are critical components in the containment of
      immunodeficiency virus infections. While the protective role of CD8+ T cells is
      well established by studies of CD8+ T cell-mediated viral escape, it remains
      unknown if CD4+ T cells can also impose sufficient selective pressure on
      replicating virus to drive the emergence of high-frequency escape variants.
      Identifying a high frequency CD4+ T cell driven escape mutation would provide
      compelling evidence of direct immunological pressure mediated by these cells.
      RESULTS: Here, we studied a SIVmac239-infected elite controller rhesus macaque
      with a 1,000-fold spontaneous increase in plasma viral load that preceded disease
      progression and death from AIDS-related complications. We sequenced the viral
      genome pre- and post-breakthrough and demonstrate that CD8+ T cells drove the
      majority of the amino acid substitutions outside of Env. However, within a region
      of Gag p27CA targeted only by CD4+ T cells, we identified a unique post
      breakthrough mutation, Gag D205E, which abrogated CD4+ T cell recognition.
      Further, we demonstrate that the Gag p27CA-specific CD4+ T cells exhibited
      cytolytic activity and that SIV bearing the Gag D205E mutation escapes this CD4+
      T cell effector function ex vivo. CONCLUSIONS: Cumulatively, these results
      confirm the importance of virus specific CD8+ T cells and demonstrate that CD4+ T
      cells can also exert significant selective pressure on immunodeficiency viruses
      in vivo during low-level viral replication. These results also suggest that
      further studies of CD4+ T cell escape should focus on cases of elite control with
      spontaneous viral breakthrough.

PMID- 23131038
TI  - Plasmacytoid dendritic cell number and responses to Toll-like receptor 7 and 9
      agonists vary in HIV Type 1-infected individuals in relation to clinical state.
AB  - In HIV-1 infection, plasmacytoid dendritic cell (PDC) numbers and function are
      decreased. No detailed comparisons of PDC responses to various stimuli in HIV-1
      infected patients are available. Using for the first time purified PDCs, we
      compared PDC responses [interferon (IFN)-alpha production/cell] to various
      stimuli in a large number (n=48) of HIV-1-infected patients and healthy
      volunteers (n=19). Toll-like receptor (TLR)7- and TLR9-induced expression of PDC
      surface activation and maturation markers was also compared in the two
      populations. We have confirmed that PDC number coincides with CD4(+) T cell
      counts and clinical state. Notably, we have shown that a direct association of
      PDC function in terms of IFN-alpha production/cell exists with PDC numbers and
      CD4(+) cell counts when PDCs are exposed to a TLR9 ligand and HIV-infected cells,
      but not with a TLR7 ligand. Moreover, in the HIV-infected subjects but not the
      healthy controls, the magnitude of IFN-alpha release per PDC in response to the
      TLR7 ligand is significantly (p<0.01) lower than that to the TLR9 ligand.
      However, in both study populations, the TLR7 stimulation in comparison to TLR9
      stimulation induced higher expression of PDC surface activation and maturation
      markers and significantly (p<0.05) decreased the expression of BDCA-2, a negative
      regulator of interferon. Furthermore, the cross-ligation of BDCA-2 significantly
      (p<0.05) inhibited TLR9- but not TLR7-induced IFN-alpha production by PDCs from
      both clinical groups. These findings suggest that differences exist in TLR7- and
      TLR9-induced IFN-alpha production by PDCs in HIV-infected individuals that are
      not directly related to BDCA-2 down-modulation.

PMID- 23131040
TI  - Molecular products and radicals from pyrolysis of lignin.
AB  - Thermal degradation of lignin under two reaction regimes (pyrolysis in N(2) and
      oxidative pyrolysis in 4% O(2) in N(2)) has been investigated in a tubular,
      isothermal, flow-reactor over the temperature range 200-900  degrees C at a
      residence time of 0.2 s. Two experimental protocols were adopted: (1) Partial
      pyrolysis in which the same lignin sample was continuously pyrolyzed at each
      temperature and (2) conventional pyrolysis, in which new lignin samples were
      pyrolyzed at each pyrolysis temperature. The results identified common
      relationships between the two modes of experiments, as well as some differences.
      The majority of products from partial pyrolysis peaked between 300 and 500 
      degrees C, whereas for conventional pyrolysis reaction products peaked between
      400 and 500  degrees C. The principal products were syringol (2,6-dimethoxy
      phenol), guaiacol (2-methoxy phenol), phenol, and catechol. Of the classes of
      compounds analyzed, the phenolic compounds were the most abundant, contributing
      over 40% of the total compounds detected. Benzene, styrene, and p-xylene were
      formed in significant amounts throughout the entire temperature range.
      Interestingly, six ringed polycyclic aromatic hydrocarbons were formed during
      partial pyrolysis. Oxidative pyrolysis did not result in large differences from
      pyrolysis; the main products still were syringol, guaiacol, phenol, the only
      significant difference being the product distribution peaked between 200 and 400 
      degrees C. For the first time, low temperature matrix isolation electron
      paramagnetic resonance was successfully interfaced with the pyrolysis reactor to
      elucidate the structures of the labile reaction intermediates. The EPR results
      suggested the presence of methoxyl, phenoxy, and substituted phenoxy radicals as
      precursors for formation of major products; syringol, guaiacol, phenols, and
      substituted phenols.

PMID- 23131041
TI  - Quantitative trait locus mapping of genes associated with vacuolation in the
      adrenal X-zone of the DDD/Sgn inbred mouse.
AB  - BACKGROUND: Adrenal gland of mice contains a transient zone between the adrenal
      cortex and the adrenal medulla: the X-zone. There are clear strain differences in
      terms of X-zone morphology. Nulliparous females of the inbred mouse DDD strain
      develop adrenal X-zones containing exclusively vacuolated cells, whereas females
      of the inbred mouse B6 strain develop X-zones containing only non-vacuolated
      cells. The X-zone vacuolation is a physiologic process associated with the X-zone
      degeneration and is tightly regulated by genetic factors. Identification of the
      genetic factors controlling such strain differences should help analyze the X
      zone function. In this study, a quantitative trait locus (QTL) analysis for the
      extent of X-zone vacuolation was performed for two types of F2 female mice: F2Ay
      mice (F2 mice with the Ay allele) and F2 non-Ay mice (F2 mice without the Ay
      allele). These were produced by crossing B6 females and DDD.Cg-Ay males. DDD.Cg
      Ay is a congenic mouse strain for the Ay allele at the agouti locus and is used
      for this study because a close association between the X-zone morphology and the
      agouti locus genotype has been suggested. The Ay allele is dominant and
      homozygous lethal; therefore, living Ay mice are invariably heterozygotes.
      RESULTS: Single QTL scans identified significant QTLs on chromosomes 1, 2, 6, and
      X for F2 non-Ay mice, and on chromosomes 2, 6, and 12 for F2Ay mice. The QTL on
      chromosome 2 was considered to be because of the agouti locus, which has been
      suggested to be associated with X-zone vacuolation. A significant QTL that
      interacted with the agouti locus was identified on chromosome 8. CONCLUSIONS: The
      extent of X-zone vacuolation in DDD females was controlled by multiple genes with
      complex interactions. The murine X-zone is considered analogous structure to the
      human fetal zone. Therefore, the results of this study will aid in understanding
      function of not only of the X-zone but also of the human fetal zone. Identifying
      the genes responsible for the QTLs will be essential for understanding the
      molecular basis of X-zone function, which is currently unclear.

PMID- 23131042
TI  - Evaluation of the metabolism and hepatotoxicity of xenobiotics utilizing
      precision-cut slices.
AB  - 1. Precision-cut liver slices are a valuable in vitro model system to study the
      metabolism and toxicity of xenobiotics. Liver slices retain tissue architecture
      so that all cell types are present and intercellular communication between the
      various cell types is retained.   2. Precision-cut liver slices from humans and
      other species have been used to study pathways of phase I (e.g. cytochrome P450
      dependent biotransformations) and II (e.g. conjugation with D-glucuronic acid,
      sulphate and glutathione) metabolism of a wide range of xenobiotics.   3. Liver
      slices can also be employed to investigate the induction and inhibition of
      xenobiotic metabolizing enzymes and to obtain kinetic data on the rates of
      metabolism of xenobiotics.   4. Precision-cut liver slices from humans and other
      species have been used to study the toxicity of a wide variety of xenobiotics.
      Toxicity can be assessed by various techniques including gene expression,
      morphological examination and a wide range of biochemical endpoints.   5.
      Precision-cut liver slices can be utilized to examine species differences in
      hepatic xenobiotic metabolism and xenobiotic-induced toxicity, thus permitting
      comparisons between animal species and humans.

PMID- 23131043
TI  - UV-Vis identification and DFT-assisted prediction of structures of Cu(II)-alkyl
      chlorocomplexes.
AB  - The structures of paramagnetic copper complexes, the products of photolysis of
      tetrachlorocuprates of quaternary ammonium in frozen solvents, earlier denoted as
      1-Cu and 2-Cu, were established on the basis of comparison of experimental and
      theoretical UV-vis spectra. UV-vis spectra of photolysis products were registered
      at 77-116 K. Comparison with the EPR data in this temperature range allowed to
      assign photolysis products bands in the vis spectrum either to 1-Cu or to 2-Cu.
      Model structures for 1-Cu and 2-Cu were proposed. TD-DFT calculated spectra of
      model compounds along with CuCl(4)(2-) anion are in excellent agreement with the
      experiment. The comparison of UV-vis and EPR data and results of TD-DFT
      calculations evidence that 1-Cu and 2-Cu are paramagnetic
      organochlorocuprates(II) with general formulas Cu(II)Cl(2)R and Cu(II)Cl(3)R,
      respectively, where R is (-C(6)H(12))N(+)(C(6)H(13))(3).

PMID- 23131044
TI  - Interconversion of the pallambins through photoinduced rearrangement.
AB  - A new photoinduced interconversion of four naturally occurring 19-nor-7,8
      secolabdane diterpenoids was discovered and analyzed. The photochemical
      mechanism, intramolecular diradical rearrangement reaction, was investigated by
      time-lapse monitoring of the end product formations with HPLC and UV, as well as
      detailed theoretical calculations.

PMID- 23131045
TI  - Perspective on cost-effective utilization of cardiac resynchronization therapy.

PMID- 23131047
TI  - Comparison of the efficacy of three concentrations of retinoic acid for
      transdifferentiation induction in sheep marrow-derived mesenchymal stem cells
      into male germ cells.
AB  - Recent studies have shown the unique role of retinoic acid (RA) in the induction
      of transdifferentiation in mesenchymal stem cells (MSCs) into germ cells (GCs).
      This study is the first study that compares the efficacy of three different
      concentrations of RA for the production of male GCs in vitro. Male sheep marrow
      derived MSCs (MMSCs) were treated with the following concentrations of RA: 1 MUm
      (RA1), 5 MUm (RA2) and 10 MUm (RA3) for a period of 21 days. The production of
      male GCs was evaluated by the assessment of expressions of GC-specific markers
      (by RT-PCR, qRT-PCR and immunocytochemistry), morphological characteristics and
      changes in alkaline phosphatase (ALP) activity. All three concentrations created
      male GC features. RA treatment upregulated the expressions of VASA and beta1
      INTEGRIN and downregulated PIWIL2 and OCT4. DAZL was not expressed by RA
      treatment. Interestingly, immunocytochemistry detected PGP 9.5 expression in all
      treatment groups, with the highest expression noted in the RA3 group (P < 0.05).
      GC-like cells along with increased ALP activity were observed in all treated
      cultures, too. Finally, results showed that 10 MUm RA has the most efficiency for
      transdifferentiation induction in MMSCs and production of male GCs in vitro.

PMID- 23131048
TI  - Rapid formation of a dense sulfur layer on gold through use of triphenylmethane
      sulfenyl chloride as a precursor.
AB  - The use of triphenylmethane sulfenyl chloride as a new precursor leads to the
      efficient deposition of sulfur on polycrystalline gold and Au(111) substrates.
      The modified surfaces are characterized using X-ray photoelectron spectroscopy
      (XPS), electrochemistry and scanning tunneling microscopy (STM). The XPS data
      shows the rapid deposition of polymeric sulfur within very short times.
      Electrochemical stripping cyclic voltammetry (CV) confirms the rapid deposition
      and shows that high coverage values are achieved. STM imaging shows the formation
      of a wide range sulfur layer and production of the well-known etch pits. High
      resolution STM images confirm the high density of the sulfur layers and show
      formation of a long-range phase consisting of rhombus structures close to the
      previously described rectangular structures along with other parallelograms and
      partial parallelograms. The present results do not show the initial formation of
      any organic self-assembled monolayer (SAM) indicating that the formation of
      polymeric sulfur does not result from the decomposition of an initial SAM as
      previously observed with alkyl and aryl thiolate-based SAMs. The suggested
      mechanism involves an initial reductive process similar to the one reported for
      thiocyanates and sulfenyl chlorides. This is followed by the dissociation of the
      Ph(3)C-S bond, leaving only sulfur on the surface, through a process leading to
      the recombination of the remaining fragments to yield triphenylmethyl chloride.

PMID- 23131049
TI  - Photodegradation of the isoxazolidine fungicide SYP-Z048 in aqueous solution:
      kinetics and photoproducts.
AB  - Previous research has demonstrated that 3-[5-(4-chlorophenyl)-2,3-dimethyl-3
      isoxazolidinyl]pyridine (SYP-Z048), a newly developed nitrogen heterocycle
      substituted isoxazolidine compound, has good protective and curative activities
      against a wide range of fungal diseases of fruits and vegetables caused by
      Ascomycetes, Basidiomycetes, and Deuteromycetes. In this study, the photochemical
      behavior of SYP-Z048 was investigated in aqueous solution and in response to
      solar and low-pressure mercury ultraviolet (UV) lamp irradiation. SYP-Z048
      photolysis was pH- and temperature-dependent and was described by a first-order
      degradation reaction. A total of 11 photoproducts were separated by high
      performance liquid chromatography (HPLC) and solid-phase extraction (SPE) and
      were identified on the basis of (1)H and (13)C nuclear magnetic resonance (NMR)
      and high-performance liquid chromatography-mass spectrometry (HPLC-MS) spectra.
      The photoproduct structures and kinetics suggested that the phototransformation
      of SYP-Z048 occurred via multiple reaction pathways that included the cleavage of
      the N-O bond in the isoxazolidine ring and the dechlorination of the benzene
      ring.

PMID- 23131050
TI  - LTRsift: a graphical user interface for semi-automatic classification and
      postprocessing of de novo detected LTR retrotransposons.
AB  - BACKGROUND: Long terminal repeat (LTR) retrotransposons are a class of
      eukaryotic mobile elements characterized by a distinctive sequence similarity
      based structure. Hence they are well suited for computational identification.
      Current software allows for a comprehensive genome-wide de novo detection of such
      elements. The obvious next step is the classification of newly detected
      candidates resulting in (super-)families. Such a de novo classification approach
      based on sequence-based clustering of transposon features has been proposed
      before, resulting in a preliminary assignment of candidates to families as a
      basis for subsequent manual refinement. However, such a classification workflow
      is typically split across a heterogeneous set of glue scripts and generic
      software (for example, spreadsheets), making it tedious for a human expert to
      inspect, curate and export the putative families produced by the workflow.
      RESULTS: We have developed LTRsift, an interactive graphical software tool for
      semi-automatic postprocessing of de novo predicted LTR retrotransposon
      annotations. Its user-friendly interface offers customizable filtering and
      classification functionality, displaying the putative candidate groups, their
      members and their internal structure in a hierarchical fashion. To ease manual
      work, it also supports graphical user interface-driven reassignment, splitting
      and further annotation of candidates. Export of grouped candidate sets in
      standard formats is possible. In two case studies, we demonstrate how LTRsift can
      be employed in the context of a genome-wide LTR retrotransposon survey effort.
      CONCLUSIONS: LTRsift is a useful and convenient tool for semi-automated
      classification of newly detected LTR retrotransposons based on their internal
      features. Its efficient implementation allows for convenient and seamless
      filtering and classification in an integrated environment. Developed for life
      scientists, it is helpful in postprocessing and refining the output of software
      for predicting LTR retrotransposons up to the stage of preparing full-length
      reference sequence libraries. The LTRsift software is freely available at
      http://www.zbh.uni-hamburg.de/LTRsift under an open-source license.

PMID- 23131051
TI  - A glimpse at the cerebrospinal fluid immunoglobulins in neurological conditions.
      Does it help the clinician?

PMID- 23131052
TI  - Preoperative serum sodium is associated with cancer-specific survival in patients
      with upper urinary tract urothelial carcinoma treated by nephroureterectomy.
AB  - OBJECTIVES: To assess the impact of preoperative serum sodium concentration on
      the prognosis of patients with upper urinary tract urothelial carcinoma treated
      by nephroureterectomy. METHODS: The clinical records of 139 patients treated for
      upper urinary tract urothelial carcinoma by nephroureterectomy were
      retrospectively reviewed. Recurrence-free and cancer-specific survival curves
      were calculated using the Kaplan-Meier method, with the difference between curves
      evaluated using the log-rank test. A multivariate analysis was carried out by
      Cox's proportional hazard model to identify prognostic factors. RESULTS: The
      median (range) follow-up time was 27 (1-139) months. The median (range)
      preoperative serum sodium was 141 (134-147) mEq/L. Five-year cancer-specific
      survival estimates for patients above and below the median preoperative serum
      sodium were 81.7% (95% confidence interval: 68.7-89.7) and 50.6% (95% confidence
      interval: 30.3-67.8), respectively. In the multivariate analysis, preoperative
      sodium concentration, pathological T stage, and lymphovascular invasion were
      independent and significant prognostic factors for cancer-specific survival. A
      prognostic model of risk classification for cancer-specific survival involving
      these parameters was developed, and 5-year cancer-specific survival estimates
      were 29.9% (95% confidence interval: 14.5-47.0) for the poor risk group (hazard
      ratio 19.95 [95% confidence interval: 8.5-46.6]; P < 0.001), 81.6% (95%
      confidence interval: 55.2-93.3) for the intermediate risk group (hazard ratio
      5.70 [95% confidence interval: 1.27-25.5]; P = 0.022) and 97.9% (95% confidence
      interval 85.9-99.7) for the favorable risk group. CONCLUSION: These findings
      suggest for the first time that a low preoperative sodium level predicts a poor
      survival in upper urinary tract urothelial carcinoma patients treated by
      nephroureterectomy.

PMID- 23131053
TI  - Current status of donation after cardiac death in children in China.

PMID- 23131054
TI  - Endoscopy in the management of pancreaticobiliary complications after liver,
      intestine, or composite visceral transplantation in children.

PMID- 23131055
TI  - The kidney in pediatric liver transplantation: an updated perspective.
AB  - CKD continues to detract from the success of improved survival in pediatric liver
      transplantation, and its presence is likely under recognized. Here we review the
      literature regarding the prevalence, etiology, and management of renal
      dysfunction in pediatric liver transplant recipients. Long-term studies suggest
      the prevalence of CKD to be 25-38% by 5-10 yr post-transplant. While important,
      sole use of serum creatinine overestimates renal function in this population.
      Screening for and treatment of persistent proteinuria and hypertension as well as
      minimization of nephrotoxic insults are the mainstays to delay or prevent CKD
      progression. Office-based blood pressure measures are less sensitive than ABPM,
      which is specifically recommended by the American Heart Association for its
      ability to diagnose masked hypertension in pediatric liver transplant recipients.
      Long-term risk of CKD is predominantly secondary to CNI toxicity. CNI
      minimization protocols have shown promise in slowing progression of CKD while
      maintaining graft function, but large-scale randomized control trials with long
      term follow-up are needed.

PMID- 23131056
TI  - Metabolic syndrome and endocrine dysfunctions after HSCT in children.
AB  - MS and endocrine dysfunction(s) are common well-recognized complications after
      HSCT. We retrospectively analyzed our data on 160 patients with a median age at
      transplant of five yr (0.3-23), who had been followed for a median of seven yr
      (range 3-18) at Nationwide Children's Hospital after transplant. Dyslipidemia and
      MS were seen in 13% and 7.5% patients, respectively, and 58% of these patients
      were <20 yr of age. Twelve patients met the criteria for diagnosis of MS, but
      four of these did not meet the International Diabetic Federation or WHO criteria.
      Variation in the diagnostic criteria for MS leading to underdiagnosis is
      discussed. Female gonadal failure (27%) and hypothyroidism (21%) were the most
      common endocrine dysfunctions, followed by short stature and GH deficiency (17%)
      each. TBI and younger age at HSCT were associated with the highest burden of long
      term effects, and female sex was more significantly associated with MS-related
      dysfunction (p < 0.05). Uniform diagnostic criteria for MS and close follow-up
      after transplant are important for the early diagnosis and management of these
      late effects, thereby improving the overall quality of life of these patients.

PMID- 23131057
TI  - Acute graft-versus-host disease in pediatric allogeneic hematopoietic stem cell
      transplantation. Single-center experience during 10 yr.
AB  - a-GvHD may complicate allogeneic HSCT. In this retrospective single-center study,
      we evaluated incidence and risk factors of a-GvHD in 197 consecutive allogeneic
      pediatric HSCTs applying Glucksberg and NIH a-GvHD classifications. Among 179
      eligible transplants, the cumulative incidence of grade 0-I a-GvHD was 48% and
      grade II-IV was 52%. None of the considered variables significantly influenced
      the incidence of grade II-IV a-GvHD. Malignancy and myeloablation were associated
      with an increased risk of classic a-GvHD (p < 0.01). Seventy-two percentage of
      children are alive, with a significant difference in OS and TRM between grade 0
      and I vs. grade II and IV a-GvHD; this observation was reproduced in the non
      malignant setting, while only a disparity in TRM was evidenced in children with
      malignancy. In our experience, the incidence of a-GvHD was similar, regardless of
      donor type. Myeloablation and malignant disease represented the only risk factors
      for classic a-GvHD. Our results highlight the need for a better prevention of
      this complication in the non-malignant setting.

PMID- 23131058
TI  - Long-term outcomes of living donor kidney transplants in pediatric recipients
      following laparoscopic vs. open donor nephrectomy.
AB  - We compared long-term outcomes of LDKT in pediatric recipients following either
      laparoscopic (LDN) or ODN. In our retrospective single-center study, we compared
      38 pediatric LDKT recipients of a laparoscopically procured kidney with a
      historic ODN group comprising 17 pediatric recipients. In our center, the first
      pure laparoscopic non-hand-assisted LDN for a pediatric LDKT recipient was
      performed in June 2001. Demographic data of donors and recipients were comparable
      between groups. Mean follow-up was 64 months in the LDN group and 137 months in
      the ODN group. Patient survival was comparable between groups. Graft survival at
      one and five yr was 97% (LDN) vs. 94% (ODN) and 91% (LDN) vs. 88% (ODN; p =
      n.s.), respectively. Serum creatinine at one and five yr was 1.16 +/- 0.47 mg/dL
      (LDN) vs. 1.02 +/- 0.38 mg/dL (ODN) and 1.38 +/- 0.5 mg/dL (LDN) vs. 1.20 +/-
      0.41 mg/dL (ODN), respectively. The type and frequency of surgical complications
      did not differ between groups. DGF and acute rejection rates were similar between
      groups. In the ODN group, a higher proportion of right donor kidneys was used. In
      the ODN group, all kidneys had singular arteries, whereas in the LDN group five
      kidneys had multiple arteries. Arterial multiplicity was associated with a higher
      incidence of DGF. In our experience, LDN does not compromise long-term graft
      outcomes in pediatric LDKT recipients. Arterial multiplicity of the donor kidney
      may be a risk factor for impaired early graft function in the pediatric
      population.

PMID- 23131059
TI  - Lipid metabolism and oxidative stress in children after liver transplantation
      treated with sirolimus.
AB  - Lipid disturbances are one of the most frequent side effects of SRL; however,
      clinical consequences are not known. The aim of the study was to evaluate the
      risk of AS in children after LTx treated with SRL. In 17 children with median age
      13.2 yr (1.9-17.9) who received SRL on average for 4.1 yr (s.d. +/- 2.9) we
      measured and compared with age-matched healthy control group (n = 45) lipid
      parameters and markers of AS: ADMA, oxyLDL, GSH, GPx, TC, TG, HDL cholesterol,
      LDL cholesterol, VLDL cholesterol, ApoAI, ApoB, ApoE, lipoprotein (a) (Lp(a)). We
      found no major differences in cholesterol, cholesterol in lipoprotein fractions
      and TG concentrations between patients receiving SRL and the control group. ApoE
      was markedly increased in the study group (19.1 g/L [+/-1.8]) when compared to
      controls (9.8 [+/-3.9]). ApoA1 was decreased in the study group: 1.30 g/L (+/
      0.2) vs. 1.45 (+/-0.25), p = 0.04. ApoB and Lpa concentrations were similar in
      both groups. There were differences in oxidative stress markers: GSH 743 (+/
      66.2) mol/mL vs. 780 (+/-48.2), p = 0.02 and GPx 32.8 (+/-5.5) U/gHb vs. 34.3(+/
      2.6), p = 0.01. Markers of AS: ADMA did not differ between groups and oxidized
      LDLc was significantly lower in SRL group: 190 mU/mL (+/-113) vs. 237 (+/-107) in
      control, p < 0.05. SRL does not significantly disturb lipid metabolism and
      oxidative status in children after LTx.

PMID- 23131060
TI  - Brain growth in preterm infants is affected by the degree of growth restriction
      at birth.
AB  - OBJECTIVE: Documentation of examination of brain structural development by
      magnetic resonance imaging (MRI) beyond the neonatal period is scarce for both
      preterm and small for gestational age (SGA) infants. AIM: To investigate
      structural brain development during infancy in preterm children born SGA by MRI.
      METHODS: A total of 205 preterm infants, 139 appropriate for gestational age
      (AGA) and 66 SGA, of which 33 had birth weight (BW) < 3rd percentile and 33 had
      BW 3rd-10th percentile, were examined prospectively by brain MRI at the corrected
      age of 5 months. The total volume of the brain, ventricles and cerebellum, the
      area of vermis and corpus callosum, and the height of the pituitary,
      mesencephalon and pons were estimated on MRI. RESULTS: Brain volume was smaller
      in the SGA < 3rd percentile infants, independent of other perinatal factors.
      Chronic lung disease was an independent predictor of low brain volume. Pituitary
      height was greater in SGA < 3rd percentile than in AGA infants. The corpus
      callosum area was less in SGA < 3rd percentile than in SGA of 3rd-10th percentile
      infants. CONCLUSIONS: Preterm infants born SGA with BW < 3rd percentile had
      differences in brain structural measurements at the corrected age of 5 months,
      compared with preterm AGA infants, which could have implications for their
      neurocognitive development.

PMID- 23131062
TI  - Bimodal gold nanoparticle therapeutics for manipulating exogenous and endogenous
      protein levels in mammalian cells.
AB  - A new advance in cell transfection protocol using a bimodal nanoparticle agent to
      selectively manipulate protein expression levels within mammalian cells is
      demonstrated. The nanoparticle based transfection approach functions by
      controlled release of gene regulatory elements from a 6 nm AuNP (gold
      nanoparticle) surface. The endosomal release of the regulatory elements from the
      nanoparticle surface results in endogenous protein knockdown simultaneously with
      exogenous protein expression for the first 48 h. The use of fluorescent proteins
      as the endogenous and exogenous signals for protein expression enables the
      efficiency of codelivery of siRNA (small interfering RNA) for GFP (green
      fluorescent protein) knockdown and a dsRed-express linearized plasmid for
      induction to be optically analyzed in CRL-2794, a human kidney cell line
      expressing an unstable green fluorescent protein. Delivery of the bimodal
      nanoparticle in cationic liposomes results in 20% GFP knockdown within 24 h of
      delivery and continues exhibiting knockdown for up to 48 h for the bimodal agent.
      Simultaneous dsRed expression is observed to initiate within the same time frame
      with expression levels reaching 34% after 25 days although cells have divided
      approximately 20 times, implying daughter cell transfection has occurred.
      Fluorescence cell sorting results in a stable colony, as demonstrated by Western
      blot analysis. The simultaneous delivery of siRNA and linearized plasmid DNA on
      the surface of a single nanocrystal provides a unique method for definitive
      genetic control within a single cell and leads to a very efficient cell
      transfection protocol.

PMID- 23131061
TI  - Primary radiation defect production in polyethylene and cellulose.
AB  - Irradiation effects in polyethylene and cellulose were examined using molecular
      dynamics simulations. The governing reactions in both materials were chain
      scissioning and generation of small hydrocarbon and peroxy radicals.
      Recombination of chain fragments and cross-linking between polymer chains were
      found to occur less frequently. Crystalline cellulose was found to be more
      resistant to radiation damage than crystalline polyethylene. Statistics on
      radical formation are presented and the dynamics of the formation of radiation
      damage discussed.

PMID- 23131063
TI  - Study design of the man and machine trial: a prospective international controlled
      noninferiority trial comparing manual with robotic catheter ablation for
      treatment of atrial fibrillation.
AB  - BACKGROUND: Pulmonary vein isolation (PVI) has become the cornerstone procedure
      for the treatment of symptomatic drug-resistant atrial fibrillation (AF). At the
      present time, circumferential PVI (CPVI) using irrigated radiofrequency (RF) is
      the mostly used ablation technique. However, for CPVI, precise catheter
      navigation and excellent catheter stability is crucial thereby requiring
      experienced operators. Robotic navigation systems have been introduced to
      facilitate catheter navigation and to improve catheter stability, therefore
      potentially increasing procedural success and making CPVI accessible to less
      experienced operators. To date, no prospective randomized trial has evaluated the
      efficacy and safety of CPVI using RNS compared to manually performed ablation.
      METHODS: In this prospective international multicenter noninferiority trial, 258
      patients with either paroxysmal or short-standing persistent AF will be
      randomized for comparison of PVI using either manual or robotic ablation. In all
      patients, CPVI will be performed using irrigated RF ablation in combination with
      a 3D mapping system. The primary endpoint of the trial is the absence of AF or
      atrial tachycardia without antiarrhythmic drug therapy during 12-month follow-up.
      Secondary endpoints will be evaluation of periprocedural complications and
      procedural data such as procedure time, fluoroscopy time, as well as the
      incidence of esophageal injury assessed by endoscopy within 48 hours after the
      procedure. CONCLUSION: The "Man and Machine Trial" is the first prospective
      international randomized controlled multicenter noninferiority trial to compare
      manually performed CPVI with robotically navigated CPVI, evaluating both the
      safety and efficacy of the 2 techniques during a 12-month follow-up period.

PMID- 23131064
TI  - A protocol for a trial of homeopathic treatment for irritable bowel syndrome.
AB  - BACKGROUND: Irritable bowel syndrome is a chronic condition with no known cure.
      Many sufferers seek complementary and alternative medicine including homeopathic
      treatment. However there is much controversy as to the effectiveness of
      homeopathic treatment. This three-armed study seeks to explore the effectiveness
      of individualised homeopathic treatment plus usual care compared to both an
      attention control plus usual care and usual care alone, for patients with
      irritable bowel syndrome. METHODS/DESIGN: This is a three-armed pragmatic
      randomised controlled trial using the cohort multiple randomised trial
      methodology. Patients are recruited to an irritable bowel syndrome cohort from
      primary and secondary care using GP databases and consultants lists respectively.
      From this cohort patients are randomly selected to be offered, 5 sessions of
      homeopathic treatment plus usual care, 5 sessions of supportive listening plus
      usual care or usual care alone. The primary clinical outcome is the Irritable
      Bowel Syndrome Symptom Severity at 26 weeks.From a power calculation, it is
      estimated that 33 people will be needed for the homeopathic treatment arm and 132
      for the usual care arm, to detect a minimal clinical difference at 80 percent
      power and 5 percent significance allowing for loss to follow up. An unequal group
      size has been used for reasons of cost. Analysis will be by intention to treat
      and will compare homeopathic treatment with usual care at 26 weeks as the primary
      analysis, and homeopathic treatment with supportive listening as an additional
      analysis. DISCUSSION: This trial has received NHS approval and results are
      expected in 2013. TRIAL REGISTRATION: Current Controlled Trials ISRCTN90651143.

PMID- 23131065
TI  - Improved programming of ICDs.

PMID- 23131067
TI  - Circadian oscillations of molecular clock components in the cerebellar cortex of
      the rat.
AB  - The central circadian clock of the mammalian brain resides in the suprachiasmatic
      nucleus (SCN) of the hypothalamus. At the molecular level, the circadian
      clockwork of the SCN constitutes a self-sustained autoregulatory feedback
      mechanism reflected by the rhythmic expression of clock genes. However, recent
      studies have shown the presence of extrahypothalamic oscillators in other areas
      of the brain including the cerebellum. In the present study, the authors unravel
      the cerebellar molecular clock by analyzing clock gene expression in the
      cerebellum of the rat by use of radiochemical in situ hybridization and
      quantitative real-time polymerase chain reaction. The authors here show that all
      core clock genes, i.e., Per1, Per2, Per3, Cry1, Cry2, Clock, Arntl, and Nr1d1, as
      well as the clock-controlled gene Dbp, are expressed in the granular and Purkinje
      cell layers of the cerebellar cortex. Among these genes, Per1, Per2, Per3, Cry1,
      Arntl, Nr1d1, and Dbp were found to exhibit circadian rhythms in a sequential
      temporal manner similar to that of the SCN, but with several hours of delay. The
      results of lesion studies indicate that the molecular oscillatory profiles of
      Per1, Per2, and Cry1 in the cerebellum are controlled, though possibly
      indirectly, by the central clock of the SCN. These data support the presence of a
      circadian oscillator in the cortex of the rat cerebellum.

PMID- 23131069
TI  - Characterization of chemical speciation in ultrathin uranium oxide layered films.
AB  - A unique approach to detect chemical speciation and distribution on nanometer
      scale nuclear materials has been achieved by the combination of neutron
      reflectometry and shell-isolated surface-enhanced Raman spectroscopy. Both
      surface and underlying layers of the uranium oxide materials were determined with
      angstrom-level resolution. Our results reveal that the UO(x) film is composed of
      three sublayers: an ~38 A thick layer of U(3)O(8) formed along the
      UO(x)/substrate interface; the adjacent sublayer consists of an ~900 A thick
      single phase of alpha-UO(3), and the top layer is gamma-UO(3) with a thickness of
      ~115 A.

PMID- 23131068
TI  - Impact of emergency medical helicopter transport directly to a university
      hospital trauma center on mortality of severe blunt trauma patients until
      discharge.
AB  - INTRODUCTION: The benefits of transporting severely injured patients by
      helicopter remain controversial. This study aimed to analyze the impact on
      mortality of helicopter compared to ground transport directly from the scene to a
      University hospital trauma center. METHODS: The French Intensive Care Research
      for Severe Trauma cohort study enrolled 2,703 patients with severe blunt trauma
      requiring admission to University hospital intensive care units within 72 hours.
      Pre-hospital and hospital clinical data, including the mode of transport,
      (helicopter (HMICU) versus ground (GMICU), both with medical teams), were
      recorded. The analysis was restricted to patients admitted directly from the
      scene to a University hospital trauma center. The main endpoint was mortality
      until ICU discharge. RESULTS: Of the 1,958 patients analyzed, 74% were
      transported by GMICU, 26% by HMICU. Median injury severity score (ISS) was 26
      (interquartile range (IQR) 19 to 34) for HMICU patients and 25 (IQR 18 to 34) for
      GMICU patients. Compared to GMICU, HMICU patients had a higher median time frame
      before hospital admission and were more intensively treated in the pre-hospital
      phase. Crude mortality until hospital discharge was the same regardless of pre
      hospital mode of transport. After adjustment for initial status, the risk of
      death was significantly lower (odds ratio (OR): 0.68, 95% confidence interval
      (CI) 0.47 to 0.98, P = 0.035) for HMICU compared with GMICU. This result did not
      change after further adjustment for ISS and overall surgical procedures.
      CONCLUSIONS: This study suggests a beneficial impact of helicopter transport on
      mortality in severe blunt trauma. Whether this association could be due to better
      management in the pre-hospital phase needs to be more thoroughly assessed.

PMID- 23131066
TI  - Reduction in inappropriate therapy and mortality through ICD programming.
AB  - BACKGROUND: The implantable cardioverter-defibrillator (ICD) is highly effective
      in reducing mortality among patients at risk for fatal arrhythmias, but
      inappropriate ICD activations are frequent, with potential adverse effects.
      METHODS: We randomly assigned 1500 patients with a primary-prevention indication
      to receive an ICD with one of three programming configurations. The primary
      objective was to determine whether programmed high-rate therapy (with a 2.5
      second delay before the initiation of therapy at a heart rate of >=200 beats per
      minute) or delayed therapy (with a 60-second delay at 170 to 199 beats per
      minute, a 12-second delay at 200 to 249 beats per minute, and a 2.5-second delay
      at >=250 beats per minute) was associated with a decrease in the number of
      patients with a first occurrence of inappropriate antitachycardia pacing or
      shocks, as compared with conventional programming (with a 2.5-second delay at 170
      to 199 beats per minute and a 1.0-second delay at >=200 beats per minute).
      RESULTS: During an average follow-up of 1.4 years, high-rate therapy and delayed
      ICD therapy, as compared with conventional device programming, were associated
      with reductions in a first occurrence of inappropriate therapy (hazard ratio with
      high-rate therapy vs. conventional therapy, 0.21; 95% confidence interval [CI],
      0.13 to 0.34; P<0.001; hazard ratio with delayed therapy vs. conventional
      therapy, 0.24; 95% CI, 0.15 to 0.40; P<0.001) and reductions in all-cause
      mortality (hazard ratio with high-rate therapy vs. conventional therapy, 0.45;
      95% CI, 0.24 to 0.85; P=0.01; hazard ratio with delayed therapy vs. conventional
      therapy, 0.56; 95% CI, 0.30 to 1.02; P=0.06). There were no significant
      differences in procedure-related adverse events among the three treatment groups.
      CONCLUSIONS: Programming of ICD therapies for tachyarrhythmias of 200 beats per
      minute or higher or with a prolonged delay in therapy at 170 beats per minute or
      higher, as compared with conventional programming, was associated with reductions
      in inappropriate therapy and all-cause mortality during long-term follow-up.
      (Funded by Boston Scientific; MADIT-RIT ClinicalTrials.gov number, NCT00947310.).

PMID- 23131070
TI  - B chromosome in the beetle Coprophanaeus cyanescens (Scarabaeidae): emphasis in
      the organization of repetitive DNA sequences.
AB  - BACKGROUND: To contribute to the knowledge of coleopteran cytogenetics,
      especially with respect to the genomic content of B chromosomes, we analyzed the
      composition and organization of repetitive DNA sequences in the Coprophanaeus
      cyanescens karyotype. We used conventional staining and the application of
      fluorescence in situ hybridization (FISH) mapping using as probes C0t-1 DNA
      fraction, the 18S and 5S rRNA genes, and the LOA-like non-LTR transposable
      element (TE). RESULTS: The conventional analysis detected 3 individuals (among 50
      analyzed) carrying one small metacentric and mitotically unstable B chromosome.
      The FISH analysis revealed a pericentromeric block of C0t-1 DNA in the B
      chromosome but no 18S or 5S rDNA clusters in this extra element. Using the LOA
      like TE probe, the FISH analysis revealed large pericentromeric blocks in eight
      autosomal bivalents and in the B chromosome, and a pericentromeric block
      extending to the short arm in one autosomal pair. No positive hybridization
      signal was observed for the LOA-like element in the sex chromosomes. CONCLUSIONS:
      The results indicate that the origin of the B chromosome is associated with the
      autosomal elements, as demonstrated by the hybridization with C0t-1 DNA and the
      LOA-like TE. The present study is the first report on the cytogenetic mapping of
      a TE in coleopteran chromosomes. These TEs could have been involved in the origin
      and evolution of the B chromosome in C. cyanescens.

PMID- 23131072
TI  - DFT study with inclusion of the Grimme potential on anatase TiO2: structure,
      electronic, and vibrational analyses.
AB  - Periodic DFT/B3LYP calculations for TiO(2) anatase bulk were carried out
      including semiempirical dispersive interactions (DFT-D2) to pure Khon-Sham DFT
      energy. From this standard methodology, van der Waals (vdW) radii were optimized
      to 1.4214 A for titanium and 1.3420 A for oxygen centers in order to achieve a
      better structural description. The results from this approach (here named
      DFT/B3LYP-D*) showed a better description for lattice constants, vibrational IR
      and Raman, energy band gaps, and bulk modulus than default DFT/B3LYP and
      DFT/B3LYP-D. The dispersion correction showed more reliable results and was
      necessary to achieve a good agreement with reported single crystal results,
      without new formalism or additional computational cost.

PMID- 23131073
TI  - InP/ZnS nanocrystals: coupling NMR and XPS for fine surface and interface
      description.
AB  - Advanced (1)H, (13)C, and (31)P solution- and solid-state NMR studies combined
      with XPS were used to probe, at the molecular scale, the composition (of the
      core, the shell, and the interface) and the surface chemistry of InP/ZnS
      core/shell quantum dots prepared via a non-coordinating solvent strategy. The
      interface between the mismatched InP and ZnS phases is composed of an amorphous
      mixed oxide phase incorporating InPO(x) (with x = 3 and predominantly 4),
      In(2)O(3), and InO(y)(OH)(3-2y) (y = 0, 1). Thanks to the analysis of the
      underlying reaction mechanisms, we demonstrate that the oxidation of the upper
      part of the InP core is the consequence of oxidative conditions brought by
      decarboxylative coupling reactions (ketonization). These reactions occur during
      both the core preparation and the coating process, but according to different
      mechanisms.

PMID- 23131071
TI  - The biased nucleotide composition of the HIV genome: a constant factor in a
      highly variable virus.
AB  - Viruses often deviate from their hosts in the nucleotide composition of their
      genomes. The RNA genome of the lentivirus family of retroviruses, including human
      immunodeficiency virus (HIV), contains e.g. an above average percentage of
      adenine (A) nucleotides, while being extremely poor in cytosine (C). Such a
      deviant base composition has implications for the amino acids that are encoded by
      the open reading frames (ORFs), both in the requirement of specific tRNA species
      and in the preference for amino acids encoded by e.g. A-rich codons. Nucleotide
      composition does obviously affect the secondary and tertiary structure of the RNA
      genome and its biological functions, but it does also influence phylogenetic
      analysis of viral genome sequences, and possibly the activity of the integrated
      DNA provirus. Over time, the nucleotide composition of the HIV-1 genome is
      exceptionally conserved, varying by less than 1% per base position per isolate
      within either group M, N, or O during 1983-2009. This extreme stability of the
      nucleotide composition may possibly be achieved by negative selection, perhaps
      conserving semi-stable RNA secondary structure as reverse transcription would be
      significantly affected for a less A-rich genome where secondary structures are
      expected to be more stable and thus more difficult to unfold.This review will
      discuss all aspects of the lentiviral genome composition, both of the RNA and of
      its derived double-stranded DNA genome, with a focus on HIV-1, the nucleotide
      composition over time, the effects of artificially humanized codons as well as
      contributions of immune system pressure on HIV nucleotide bias.

PMID- 23131075
TI  - Ultrafast librational relaxation of H2O in liquid water.
AB  - The ultrafast librational (hindered rotational) relaxation of a rotationally
      excited H2O molecule in pure liquid water is investigated by means of classical
      nonequilibrium molecular dynamics simulations and a power and work analysis. This
      analysis allows the mechanism of the energy transfer from the excited H2O to its
      water neighbors, which occurs on a sub-100 fs time scale, to be followed in
      molecular detail, i.e., to determine which water molecules receive the energy and
      in which degrees of freedom. It is found that the dominant energy flow is to the
      four hydrogen-bonded water partners in the first hydration shell, dominated by
      those partners' rotational motion, in a fairly symmetric fashion over the
      hydration shell. The minority component of the energy transfer, to these
      neighboring waters' translational motion, exhibits an asymmetry in energy
      reception between hydrogen-bond-donating and -accepting water molecules. The
      variation of the energy flow characteristics with rotational axis, initial
      rotational energy excitation magnitude, method of excitation, and temperature is
      discussed. Finally, the relation of the nonequilibrium results to equilibrium
      time correlations is investigated.

PMID- 23131076
TI  - Emerging concepts in the diagnosis and treatment of patients with
      undifferentiated angioedema.
AB  - Angioedema is a sudden, transient swelling of well-demarcated areas of the
      dermis, subcutaneous tissue, mucosa, and submucosal tissues that can occur with
      or without urticaria. Up to 25% of people in the US will experience an episode of
      urticaria or angioedema during their lifetime, and many will present to the
      emergency department with an acute attack. Most cases of angioedema are
      attributable to the vasoactive mediators histamine and bradykinin. Histamine
      mediated (allergic) angioedema occurs through a type I hypersensitivity reaction,
      whereas bradykinin-mediated (non-allergic) angioedema is iatrogenic or hereditary
      in origin.Although their clinical presentations bear similarities, the treatment
      algorithm for histamine-mediated angioedema differs significantly from that for
      bradykinin-mediated angioedema. Corticosteroids, and epinephrine are effective in
      the management of histamine-mediated angioedema but are ineffective in the
      management of bradykinin-mediated angioedema. Recent advancements in the
      understanding of angioedema have yielded pharmacologic treatment options for
      hereditary angioedema, a rare hereditary form of bradykinin-mediated angioedema.
      These novel therapies include a kallikrein inhibitor (ecallantide) and a
      bradykinin beta2 receptor antagonist (icatibant). The physician's ability to
      distinguish between these types of angioedema is critical in optimizing outcomes
      in the acute care setting with appropriate treatment. This article reviews the
      pathophysiologic mechanisms, clinical presentations, and diagnostic laboratory
      evaluation of angioedema, along with acute management strategies for attacks.

PMID- 23131077
TI  - Association between dental trauma and alcohol use among adolescents.
AB  - AIM: To investigate the association between dental trauma and alcohol use among
      adolescents between 14 and 19 years of age. MATERIALS AND METHODS: A cross
      sectional study was carried out involving a clinical exam performed by a
      calibrated researcher (intra-examiner Kappa = 0.93) and a self-administered
      questionnaire. The sample was representative of schoolchildren from the city of
      Diamantina (Brazil) and was made up of 738 adolescents. The type of school
      (public or private) was used as a socioeconomic indicator. Information on alcohol
      use (high risk and hazardous use) was acquired through the administration of the
      Alcohol Use Disorders Identification Test, which has been validated for use in
      Brazil. RESULTS: The prevalence of dental trauma was 26.6%, and the prevalence of
      dangerous alcohol use was 44.3%. Dental trauma was significantly associated with
      a high risk of problems related to alcohol intake (P = 0.031), hazardous alcohol
      use (P = 0.009) and binge drinking (P = 0.036). The results of the Poisson
      logistic regression revealed that hazardous alcohol use [PR = 1.30 (95% CI: 1.01
      1.66) P = 0.042] remained associated with dental trauma independently from age,
      gender, overjet, and type of school. CONCLUSIONS: The high prevalence of dental
      trauma found among adolescents in the city of Diamantina (Brazil) was greater
      among those at high risk for problems related to alcohol intake and was
      significantly associated with hazardous alcohol use.

PMID- 23131079
TI  - Reconsidering ultrafiltration in the acute cardiorenal syndrome.

PMID- 23131080
TI  - Sweet's syndrome with subcutaneous involvement associated with pegfilgrastim
      treatment: first reported case.
AB  - Neutrophilic panniculitis is an infrequent entity, considered by most authors as
      part of the 'neutrophilic dermatosis' spectrum. Few cases have been reported to
      be related with granulocyte colony-stimulating factor (G-CSF); we report a case
      of neutrophilic panniculitis and Sweet's syndrome lesions related with
      pegfilgrastim, a long-acting G-CSF. A 77-year-old woman with M2 acute myeloid
      leukemia was treated with chemotherapy as well as broad-spectrum antibiotics and
      antifungal drugs because of febrile neutropenia. Ten days after a single dose of
      pegfilgrastim, she developed a limited number of purple plaques on the neck, left
      leg, both arms and several indurated and slightly mobile nodules on her forearms.
      Skin biopsy of a plaque showed a diffused dermal neutrophilic infiltrate with
      dermal edema. Biopsy of a nodule showed a lobular neutrophilic panniculitis
      without vasculitis. No foreign material was found in those biopsies. No organisms
      were detected in blood, urine or tissue cultures. She was started with
      prednisolone 40 mg once a day, with dramatic improvement within the next 2 days.
      This case is noteworthy for the simultaneous appearance of Sweet's syndrome and
      neutrophilic panniculitis and it is the first case of neutrophilic panniculitis
      associated with this drug, pegfilgrastim.

PMID- 23131081
TI  - Differential patterns in the periodicity and dynamics of clock gene expression in
      mouse liver and stomach.
AB  - The rhythmic recurrence of biological processes is driven by the functioning of
      cellular circadian clocks, operated by a set of genes and proteins that generate
      self-sustaining transcriptional-translational feedback loops with a free-running
      period of about 24 h. In the gastrointestinal apparatus, the functioning of the
      biological clocks shows distinct patterns in the different organs. The aim of
      this study was to evaluate the time-related variation of clock gene expression in
      mouse liver and stomach, two components of the digestive system sharing vascular
      and autonomic supply, but performing completely different functions. The authors
      analyzed the periodicity by cosinor analysis and the dynamics of variation by
      computing the fractional variation to assess the rate of change in gene
      expression. Five-week-old male Balb/c mice were exposed to 2 wks of 12-h light/12
      h dark cycles, then kept in complete darkness for 3 d as a continuation of the
      dark span of the last light-dark cycle. The authors evaluated the expression of
      Bmal1, Clock, Cry1, Cry2, Per1, Per2, Per3, Rev-erbalpha, Rev-erbbeta, Npas2,
      Timeless, Dbp, Csnk1d, and Csnk1e by using real-time quantitative reverse
      transcriptase-polymerase chain reaction (RT-PCR) in mouse liver and stomach. A
      significant 24-h rhythmic component was found for 10 genes in the liver (Bmal1,
      Clock, Cry1, Per1, Per2, Per3, Rev-erbalpha, Rev-erbbeta, Npas2, and Dbp), and
      for 9 genes in the stomach (Bmal1, Cry1, Per1, Per2, Per3, Rev-erbalpha, Rev
      erbbeta, Npas2, and Dbp). In particular, Clock showed marked rhythm differences
      between liver and stomach, putatively due to some compensation by Npas2. The
      acrophase of the original values of Bmal1, Per2, Per3, Rev-erbalpha, Rev-erbbeta,
      Npas2, and Dbp expression was delayed in the stomach, and the average delay
      expressed as mean +/- SD was 14.30 +/- 7.94 degrees (57.20 +/- 31.78 minutes). A
      statistically significant difference was found in the acrophases of Bmal1 (p =
      .015) and Npas2 (p = .011). Fractional variations provided significant circadian
      rhythms for nine genes in the liver (Bmal1, Per1, Per2, Per3, Rev-erbalpha, Rev
      erbbeta, Npas2, Timeless, and Dbp), and for seven genes in the stomach (Bmal1,
      Clock, Per2, Rev-erbalpha, Npas2, Dbp, and Csnk1e). The acrophase of the
      fractional variations of Bmal1, Per2, Per3, Rev-erbalpha, Rev-erbbeta, and Dbp
      expression was delayed in the stomach, and the average delay expressed as mean +/
      SD was 19.10 +/- 9.39 degrees (76.40 +/- 37.59 minutes). A significantly greater
      fractional variation was found in the liver for Clock at 06:00 h (p = .034), Per1
      at 02:00 h (p = .037), and Per3 at 02:00 h (p = .029), whereas the fractional
      variation was greater in the stomach for Clock at 10:00 h (p = .016), and for
      Npas2 at 02:00 h (p = .029) and at 06:00 h (p = .044). In conclusion, liver and
      stomach show different phasing and dynamics of clock gene expression, which are
      probably related to prevailing control by different driving cues, and allow them
      to keep going the various metabolic pathways and diverse functional processes
      that they manage.

PMID- 23131078
TI  - Ultrafiltration in decompensated heart failure with cardiorenal syndrome.
AB  - BACKGROUND: Ultrafiltration is an alternative strategy to diuretic therapy for
      the treatment of patients with acute decompensated heart failure. Little is known
      about the efficacy and safety of ultrafiltration in patients with acute
      decompensated heart failure complicated by persistent congestion and worsened
      renal function. METHODS: We randomly assigned a total of 188 patients with acute
      decompensated heart failure, worsened renal function, and persistent congestion
      to a strategy of stepped pharmacologic therapy (94 patients) or ultrafiltration
      (94 patients). The primary end point was the bivariate change from baseline in
      the serum creatinine level and body weight, as assessed 96 hours after random
      assignment. Patients were followed for 60 days. RESULTS: Ultrafiltration was
      inferior to pharmacologic therapy with respect to the bivariate end point of the
      change in the serum creatinine level and body weight 96 hours after enrollment
      (P=0.003), owing primarily to an increase in the creatinine level in the
      ultrafiltration group. At 96 hours, the mean change in the creatinine level was 
      0.04+/-0.53 mg per deciliter (-3.5+/-46.9 MUmol per liter) in the pharmacologic
      therapy group, as compared with +0.23+/-0.70 mg per deciliter (20.3+/-61.9 MUmol
      per liter) in the ultrafiltration group (P=0.003). There was no significant
      difference in weight loss 96 hours after enrollment between patients in the
      pharmacologic-therapy group and those in the ultrafiltration group (a loss of
      5.5+/-5.1 kg [12.1+/-11.3 lb] and 5.7+/-3.9 kg [12.6+/-8.5 lb], respectively;
      P=0.58). A higher percentage of patients in the ultrafiltration group than in the
      pharmacologic-therapy group had a serious adverse event (72% vs. 57%, P=0.03).
      CONCLUSIONS: In a randomized trial involving patients hospitalized for acute
      decompensated heart failure, worsened renal function, and persistent congestion,
      the use of a stepped pharmacologic-therapy algorithm was superior to a strategy
      of ultrafiltration for the preservation of renal function at 96 hours, with a
      similar amount of weight loss with the two approaches. Ultrafiltration was
      associated with a higher rate of adverse events. (Funded by the National Heart,
      Lung, and Blood Institute; ClinicalTrials.gov number, NCT00608491.).

PMID- 23131082
TI  - Determination of zinc and copper in edible plants by nanometer silica coated,
      slotted quartz tube, flame atomic absorption spectrometry.
AB  - Nanometer SiO(2) was coated onto the inner wall of a slotted quartz tube atomizer
      (STAT) and then was used as a new atomizer (NSC- STAT) for the determination of
      Zn and Cu by flame atomic absorption spectrometry (FAAS). Compared to
      conventional STAT-FAAS, the analytical performance of NSC-STAT-FAAS was improved
      as follows: (a) the linear range of calibration curves was expanded from 30.0
      200.0 ng mL(-1) to 5.0-400.0 ng mL(-1) for Zn, and from 100.0-1000.0 ng mL(-1) to
      50.0-2000.0 ng mL(-1) for Cu; and (b) the characteristic concentration was
      decreased from 6.0 ng mL(-1)/1% to 2.7 ng mL(-1)/1% for Zn and from 25.0 ng mL(
      1)/1% to 10.1 ng mL(-1)/1% for Cu. NSC-STAT-FAAS was applied for the
      determination of Zn and Cu in edible plants, including herbal medicine, marine
      algae, tomato leaves (NIST 1573), and apple leaves (NIST 1515).

PMID- 23131083
TI  - Pulmonary vein isolation supported by MRI-derived 3D-augmented biplane
      fluoroscopy: a feasibility study and a quantitative analysis of the accuracy of
      the technique.
AB  - BACKGROUND: Despite the advancement of technology in electroanatomic mapping
      systems (EAMS), fluoroscopy remains a necessary, basic imaging modality for
      electrophysiology procedures. We present a feasibility study of new software that
      enables 3D-augmented fluoroscopy in biplane catheterization laboratories for
      planning and guidance of pulmonary vein isolation (PVI). The computer-assisted
      overlay registration accuracy was assessed in a clinical setting using an
      automatic calculation of overlay projection geometry that was derived from
      hardware sensors in C-arms, detectors, and patient table. METHODS: Consecutive
      patients (n = 89) underwent left atrium (LA) magnetic resonance imaging MRI scan
      prior to PVI. Ideal ablation lines encircling the ipsilateral pulmonary veins
      (PVs) at antral level were drawn onto the segmented LA surface. The 3D-model was
      superimposed onto biplane fluoroscopy and matched with angiographies of LA and
      PVs. Three-dimensional-overlay projection geometry was automatically calculated
      from C-arm, detectors, and table sensors. Accuracy of technique was assessed as
      alignment of MRI-derived 3D overlay and angiographic LA/PV anatomy. Integrity of
      registered overlay was quantified using landmark measurements. RESULTS: Alignment
      offsets were 1.3 +/- 1.5 mm in left PV, 1.2 +/- 1.5 mm in right PV, and 1.1 +/-
      1.4 mm in LA roof region. Bravais-Pearson correlation of the landmark
      measurements was r = 0.978 (s < 0.01), mean offset between landmark distance
      measurements was 1.4 +/- 0.78 mm. Average time needed for overlay registration
      was 9.5 +/- 3.5 seconds. CONCLUSIONS: MRI-derived 3D-augmented fluoroscopy
      demonstrated a high level of accuracy when compared with LA/PV angiography. The
      new system could be especially useful to guide procedures not supported by EAMS,
      such as cryotechnique PVI.

PMID- 23131084
TI  - Asymmetric total synthesis of an iboga-type indole alkaloid, voacangalactone,
      newly isolated from Voacanga africana.
AB  - A new hexacyclic iboga-type indole alkaloid, voacangalactone (1), was isolated
      from  Voacanga africana , and its structure including the absolute configuration
      was established by asymmetric total synthesis involving such key steps as the
      asymmetric Diels-Alder reaction using an aminodiene and the construction of an
      isoquinuclidine ring and an indole skeleton.

PMID- 23131085
TI  - Outcome of small intestinal submucosa graft for repair of anterior urethral
      strictures.
AB  - OBJECTIVES: To investigate the feasibility of small intestinal submucosa graft
      for the repair of selected anterior urethral strictures. METHODS: From June 2009
      to May 2011, 28 men (mean age 39 years) with anterior urethral strictures
      underwent urethroplasty using a four-layer small intestinal submucosa patch graft
      in an onlay or inlay fashion. The stricture was localized to the bulbar urethra
      in eight patients, the bulbopenile area in nine patients and the distal penile
      urethra in 10 patients. Failed hypospadias was observed in one patient. The mean
      stricture length was 4.6 cm (range 3.5-7.0 cm). RESULTS: The mean follow-up
      period was 24.8 months (range 12-30 months). No postoperative complications, such
      as infection or rejection, were related to the use of heterologous graft
      material. The patients voided well postoperatively, with peak flows between 16
      and 44 mL/s (mean 25.4 mL/s) in 26 patients. Two patients (7.1%) developed a
      urethral narrowing; this occurred at 5 months in one patient and 6 months in the
      other, and cystoscopy, which was carried out at 20 and 24 weeks, respectively,
      showed clear cicatricial tissue at the proximal anastomotic site. Dilation was
      carried out once every 4-6 months for recurrent stricture in one patient and
      lingual mucosal graft urethroplasty was carried out in the other patient at 18
      months postoperatively. Biopsies were obtained in four patients at 18, 24, 36 and
      42 weeks, respectively. Squamous epithelium with or without hyperkeratosis was
      observed on histological examination of the small intestinal submucosa-grafted
      areas. CONCLUSIONS: The small intestinal submucosa matrix appears to be a safe
      and effective reconstructive material for selective use in urethral
      reconstructive surgery.

PMID- 23131086
TI  - Synthesis and structural characterization of a family of modified hafnium tert
      butoxide for use as precursors to hafnia nanoparticles.
AB  - A series of modified, hafnium tert-butoxide ([Hf(OBu(t))4]) compounds (1-26) were
      crystallographically characterized, and representative species were then used to
      produce HfO2nanoparticles. This systematically varied family of [Hf(OR)4]
      compounds was developed from the reaction of [Hf(OBu(t))4] with a series of (i)
      Lewis basic solvents, tetrahydrofuran, pyridine, or 1-methylimidazole; (ii)
      simple phenols, HOC6H4(R)-2 or HOC6H3(R)2-2,6 where R = CH3, CH(CH3)2, or
      C(CH3)3; and (iii) complex polydentate alcohols, tetrahydrofuran methanol (H
      OTHF), pyridinecarbinol (H-OPy), and tris(hydroxymethylethane) (THME-H3). The
      solvent-modified products were crystallographically characterized as
      [Hf(OBu(t))4(solv)n] (1-3). The phenoxide (OAr)-exchanged [Hf(OBu(t))4] products
      isolated from toluene were characterized as dimeric [Hf(OAr)n(OBu(t))4-n]2 (4 and
      5) or [Hf(MU-OH)(OAr)3(HOBu(t))]2 (6 and 7) for the less sterically demanding OAr
      ligands and [Hf(OAr)n(OBu(t))4-n(HOBu(t))] (8 and 9) monomers for the larger OAr
      ligands. When Lewis basic solvents were employed, solvated monomers of varied OAr
      substitutions were observed as [Hf(OAr)n(OBu(t))4-n(solv)x], where solv = THF
      (10, 11, and 13-15) and py (16 and 19-21). The nuclearities of the remaining
      complex polydentate alcohol derivatives ranged from monomers (24, OPy) to dimers
      (22, OTHF; 23, OPy) to tetramers (25 and 26, THME). On the basis of their
      nuclearities, select members of this family of [Hf(OR)4] compounds (monomer,
      [Hf(OBu(t))4], 8; dimer, 19a, 22; tetramer, 25) were used to determine the
      validity of using [Hf(OR)4] precursors for the production of hafnia (HfO2)
      nanoparticles under solvothermal (oleylamine/oleic acid) conditions. After a 650 
      degrees C thermal treatment, the resulting powder X-ray diffraction pattern for
      each powder was found to be consistent with HfO2 (PDF 00-040-1173), and after a
      1000  degrees C treatment, larger particles of HfO2 (PDF 00-043-1017) were
      reported. Transmission electron microscopy images confirmed that nanomaterials
      had formed. Because identical processing conditions had been employed for each
      HfO2 nanomaterial, the morphological variations observed in this study may be
      attributed to the individual precursors ("precursor structure affect"). 

PMID- 23131088
TI  - The future role of genetic screening to detect newborns at risk of childhood
      onset hearing loss.
AB  - OBJECTIVE: To explore the future potential of genetic screening to detect
      newborns at risk of childhood-onset hearing loss. DESIGN: An expert led
      discussion of current and future developments in genetic technology and the
      knowledge base of genetic hearing loss to determine the viability of genetic
      screening and the implications for screening policy. RESULTS AND DISCUSSION:
      Despite increasing pressure to adopt genetic technologies, a major barrier for
      genetic screening in hearing loss is the uncertain clinical significance of the
      identified mutations and their interactions. Only when a reliable estimate of the
      future risk of hearing loss can be made at a reasonable cost, will genetic
      screening become viable. Given the speed of technological advancement this may be
      within the next 10 years. Decision-makers should start to consider how genetic
      screening could augment current screening programmes as well as the associated
      data processing and storage requirements. CONCLUSION: In the interim, we suggest
      that decision makers consider the benefits of (1) genetically testing all
      newborns and children with hearing loss, to determine aetiology and to increase
      knowledge of the genetic causes of hearing loss, and (2) consider screening
      pregnant women for the m.1555A> G mutation to reduce the risk of aminoglycoside
      antibiotic-associated hearing loss.

PMID- 23131089
TI  - Changes of N/L ratio and cortisol levels associated with experimental training in
      untrained rhesus macaques.
AB  - BACKGROUND: Animal training prior to beginning an experiment is an essential
      procedure and a very important course because it may affect the results of
      hematologic and hormonal variables and the functions influenced by those factors.
      Because this training inevitably causes animal stress, we wondered how much time
      is needed for untrained monkeys to recover from stresses associated with
      experimental training. METHODS: We measured the hematological and stress hormonal
      (e.g., cortisol) changes on weekly basis before and after experimental monkey
      chair training in newly acquired rhesus monkeys. RESULTS: The neutrophil-to
      lymphocyte (N/L) ratio significantly increased during the initial phase of the
      training and then gradually decreased after 3 weeks. Elevated serum cortisol
      levels in the initial phase also significantly decreased after 3 weeks of chair
      training. CONCLUSIONS: We conclude that at least a 3-week period is needed in
      monkey chair training for recovery from training stress. These results suggest
      that many researchers using nonhuman primates should provide enough time (>3
      weeks) for adaptation to the experimental environment prior to beginning a study.

PMID- 23131090
TI  - The quality of life construct in bipolar disorder research and practice: past,
      present, and possible futures.
AB  - The quality of life (QoL) construct is becoming more prominent in bipolar
      disorder (BD) research and practice. Uptake of the construct parallels an earlier
      trend in schizophrenia research, and coincides with growing interest in
      psychosocial components of BD's aetiology, phenomenology, and treatment. We argue
      that, although QoL and symptom measures derive from competing paradigms in mental
      health (the biopsychosocial and medical model, respectively), they are best seen
      as complementary. This pluralistic stance is clinically appropriate, and
      generates important questions for future research.

PMID- 23131091
TI  - Malfunction of subpectorally implanted cardiac resynchronization therapy
      defibrillators due to weakened header bond.
AB  - BACKGROUND: Implantable cardioverter defibrillator (ICD) implantation has
      increased significantly over the last 10 years. Concerns about the safety and
      reliability of ICD systems have been raised, with premature lead failure and
      battery malfunctions accounting for the majority of reported adverse events. We
      describe the unique mode of presentation, diagnosis, and management of cardiac
      resynchronization therapy defibrillators (CRT-D) malfunctions that were caused by
      weakened bonding between the generator and header. METHODS AND RESULTS: Between
      June 2008 and December 2009, 22 TeligenTM ICDs and 24 CognisTM CRT-Ds were
      implanted subpectorally at our institution, until a product advisory was issued.
      Of 24 CognisTM CRT-D implants, 3 patients presented with CRT-D malfunctions. All
      our cases presented with initially intermittent and then persisting increases in
      shock lead impedance, associated with nonphysiological noise in the shock
      electrogram channels. These issues were rectified by generator change.
      Postexplant laboratory analysis confirmed inadequate bonding between device
      header and titanium casing in all cases, resulting in loosening and rocking of
      the header followed by fatigue-induced fracture of the shock circuitry.
      CONCLUSION: Weakened bonding between the header and generator casing of
      subpectorally implanted CRT-Ds can result in fractures and malfunction of the HV
      circuit. Physicians monitoring patients with devices affected by the product
      advisory should remain vigilant in order to diagnose and manage similar device
      malfunction expediently.

PMID- 23131092
TI  - A first insight into the genotypic diversity of Mycobacterium tuberculosis from
      Rwanda.
AB  - BACKGROUND: Mycobacterium tuberculosis complex (MTC) is the causative agent of
      tuberculosis (TB). Globally, increasing evidence shows that in M. tuberculosis,
      transmission varies from strain to strain and that different strains exhibit a
      range of geographical and host specificities, pathogenicity, and drug
      susceptibility. Therefore rapid and accurate differentiation of the members of
      MTC is critical in guiding treatment and public health decisions. We carried out
      a study at different health units and the National Reference Laboratory in Rwanda
      identify Mycobacterium tuberculosis complex species prevalent in TB patients in
      Rwanda. We further characterized the isolates using spoligotyping in order to
      gain an insight into the strain diversity of drug resistant and susceptible
      isolates of M. tuberculosis in this setting. METHODS: A total of 151 isolates
      from culture positive sputum samples were harvested, heat killed at 80 degrees C
      for two hours, and then shipped to Makerere University College of Health
      Sciences, Uganda, for speciation and typing. Species identification was achieved
      by regions of difference (RD) analysis, while Spoligotyping was done to identify
      strain types. RESULTS: Region of difference analysis identified all the 151
      isolates as M. tuberculosis. Spoligotyping revealed predominance of the T2 family
      (58.3%, 88/151), with SIT 52 being the most prevalent strain (31.8%, 48/151).
      Among the 151 isolates, 64 (42.4%) were multidrug resistant (MDR) with 3 cases on
      mono-resistance. Of 94 retreatment cases, 48 (51.1%) were MDR and of 46 newly
      presenting cases 14 (30.4%) were MDR. There was a significant difference (p=0.01)
      in anti-TB drug resistance between new and retreatment cases in the sample.
      However, there was no significant relationship between HIV serostatus and the two
      major strain types SIT 52 (p =0.15and SIT 152  (p = 0.41). CONCLUSION:
      Mycobacterium tuberculosis is the most prevalent species of Mycobacterium
      tuberculosis complex in Rwanda, and SIT 52 (T2) the predominant strain. There is
      significantly more MDR in the retreatment cases but no significant difference was
      observed by HIV status in relation to any spoligotypes.

PMID- 23131093
TI  - Expression of inflammatory cytokines in placentas from pregnancies complicated
      with preeclampsia and HELLP syndrome.
AB  - OBJECTIVE: To investigate the expression of tumor necrosis factor-alpha (TNF
      alpha), interleukin-6 (IL-6) and interleukin-10 (IL-10) in villous trophoblast,
      syncytial knots and decidua placentas from pregnancies complicated with
      preeclampsia (PE), Hemolysis, Elevated Liver enzymes and Low Platelet count
      (HELLP) syndrome and gestational age-matched controls. METHODS: Study group
      included 35 placentas from pregnancies complicated with PE and 35 placentas from
      pregnancies with HELLP syndrome. Control group included 35 placentas from
      idiopathic preterm labor. Placentas were matched according to the gestational
      age. Expression of TNF-alpha, IL-6 and IL-10 was determined by
      immunohistochemistry and semi-quantitative HSCORE method in villous trophoblast,
      syncytial knots and decidua. Non-parametric statistics were used for analyses.
      RESULTS: There was no difference in the expression of TNF-alpha, IL-6 and IL-10
      in all the studied placental segments between PE, HELLP and gestational age
      matched control group. TNF-alpha (F = 32, 41, p < 0.001), IL-6 (F = 58, 53, p <
      0.001) and IL-10 (F = 17, 62, p < 0.001) expression was significantly different
      in different placental cell types, the highest expression of cytokines was in
      decidua. CONCLUSION: There was no difference in cytokine expression in villous
      trophoblast, syncytial knots and decidua among the studied placental groups. The
      expression of cytokines was highest in decidua in all the studied placental
      groups.

PMID- 23131094
TI  - Barriers and promoters of home-based pasteurization of breastmilk among HIV
      infected mothers in greater Dar es Salaam, Tanzania.
AB  - BACKGROUND: For the past decade, heat-treating breastmilk has been an infant
      feeding option recommended by the World Health Organization as a strategy to
      reduce vertical transmission. However, little is known about field experiences
      with it. Our primary objective was to explore the barriers and promoters of the
      implementation of breastmilk pasteurization, "flash-heating" (FH), in the real
      world setting of Dar es Salaam, Tanzania. SUBJECTS AND METHODS: Nineteen in-depth
      interviews were conducted with participants in a home-based infant feeding
      counseling intervention in which FH was promoted after 6 months of exclusive
      breastfeeding. Additionally, three focus group discussions were conducted with
      peer counselors. Interviews were transcribed, translated, and coded independently
      using NVivo 8 software (QSR International). Data were analyzed using the
      socioecological framework. RESULTS: Information and support provided by peer
      counselors were the most important promoters of initiation and continuation of
      FH; this impacted individual-, interpersonal-, and institutional-level promoters
      of success. Other promoters included perceived successful breastmilk expression,
      infant health after initiation of FH, and the inability to pay for replacement
      milks. Stigma was the most important barrier and cut across all levels of the
      framework. Other barriers included doubt about the safety or importance of
      pasteurized breastmilk, difficulties with expressing milk (often attributed to
      poor diet), and competing responsibilities. The most common suggestion for
      improving the uptake and duration of FH was community education. CONCLUSIONS:
      Given the acknowledged role of breastmilk pasteurization in the prevention of
      vertical transmission, further implementation research is needed. A multilevel
      intervention addressing barriers to FH would likely improve uptake.

PMID- 23131095
TI  - Breastfeeding as a specific value in women's lives: the experiences and decisions
      of breastfeeding women.
AB  - BACKGROUND: Worldwide, breastfeeding is recommended for every woman who gives
      birth to a child. The propensity to breastfeed varies. There is considerable
      knowledge about the experiences and circumstances that affect the decision to
      breastfeed, but knowledge about what actually generates the decision's force
      still needs to be increased. The aim of this study was to gain knowledge of how
      the decision to breastfeed is initiated and upheld. SUBJECTS AND METHODS:
      Eighteen women from three generations were interviewed, and the data were
      analyzed by qualitative content analysis. RESULTS: Six categories were revealed:
      "Task," "Instinct," "Silent Impact," "Conflicts," "Job," and "Joy." The women
      took on the Task of breastfeeding during pregnancy. The will to breastfeed was
      also recognized as an Instinct. The older women remained more in the background,
      exerting a Silent Impact. Parents' agreement that mothers remain at home and
      breastfeed for the first 6 months could be considered disturbing from a gender
      equality perspective. Competition arose between spouses, which could lead to
      Conflicts at weaning. The mothers in the study chose to stay home to do the Job
      and experience the Joy of breastfeeding. CONCLUSIONS: A summarizing theme was the
      specific life value of breastfeeding, encompassing feelings of coherence,
      pleasure, and pride, regardless of generation affiliation. As the favorable
      interplay of biological, sensual, relational, and social elements this value
      upheld the decision to breastfeed. It compensated for the effort and negative
      experiences, and as a finding, it appears to be transferable among breastfeeding
      mothers in other developed countries.

PMID- 23131096
TI  - Whole genome sequencing of the fish pathogen Francisella noatunensis subsp.
      orientalis Toba04 gives novel insights into Francisella evolution  and
      pathogenecity.
AB  - BACKGROUND: Francisella is a genus of gram-negative bacterium highly virulent in
      fishes and human where F. tularensis is causing the serious disease tularaemia in
      human. Recently Francisella species have been reported to cause mortality in
      aquaculture species like Atlantic cod and tilapia. We have completed the
      sequencing and draft assembly of the Francisella noatunensis subsp.
      orientalisToba04 strain isolated from farmed Tilapia. Compared to other available
      Francisella genomes, it is most similar to the genome of Francisella philomiragia
      subsp. philomiragia, a free-living bacterium not virulent to human. RESULTS: The
      genome is rearranged compared to the available Francisella genomes even though we
      found no IS-elements in the genome. Nearly 16% percent of the predicted ORFs are
      pseudogenes. Computational pathway analysis indicates that a number of the
      metabolic pathways are disrupted due to pseudogenes. Comparing the novel genome
      with other available Francisella genomes, we found around 2.5% of unique genes
      present in Francisella noatunensis subsp. orientalis Toba04 and a list of genes
      uniquely present in the human-pathogenic Francisella subspecies. Most of these
      genes might have transferred from bacterial species through horizontal gene
      transfer. Comparative analysis between human and fish pathogen also provide
      insights into genes responsible for pathogenecity. Our analysis of pseudogenes
      indicates that the evolution of Francisella subspecies's pseudogenes from Tilapia
      is old with large number of pseudogenes having more than one inactivating
      mutation. CONCLUSIONS: The fish pathogen has lost non-essential genes some time
      ago. Evolutionary analysis of the Francisella genomes, strongly suggests that
      human and fish pathogenic Francisella species have evolved independently from
      free-living metabolically competent Francisella species. These findings will
      contribute to understanding the evolution of Francisella species and
      pathogenesis.

PMID- 23131097
TI  - Automated degenerate PCR primer design for high-throughput sequencing improves
      efficiency of viral sequencing.
AB  - BACKGROUND: In a high-throughput environment, to PCR amplify and sequence a large
      set of viral isolates from populations that are potentially heterogeneous and
      continuously evolving, the use of degenerate PCR primers is an important
      strategy. Degenerate primers allow for the PCR amplification of a wider range of
      viral isolates with only one set of pre-mixed primers, thus increasing
      amplification success rates and minimizing the necessity for genome finishing
      activities. To successfully select a large set of degenerate PCR primers
      necessary to tile across an entire viral genome and maximize their success, this
      process is best performed computationally. RESULTS: We have developed a fully
      automated degenerate PCR primer design system that plays a key role in the J.
      Craig Venter Institute's (JCVI) high-throughput viral sequencing pipeline. A
      consensus viral genome, or a set of consensus segment sequences in the case of a
      segmented virus, is specified using IUPAC ambiguity codes in the consensus
      template sequence to represent the allelic diversity of the target population.
      PCR primer pairs are then selected computationally to produce a minimal amplicon
      set capable of tiling across the full length of the specified target region. As
      part of the tiling process, primer pairs are computationally screened to meet the
      criteria for successful PCR with one of two described amplification protocols.
      The actual sequencing success rates for designed primers for measles virus, mumps
      virus, human parainfluenza virus 1 and 3, human respiratory syncytial virus A and
      B and human metapneumovirus are described, where >90% of designed primer pairs
      were able to consistently successfully amplify >75% of the isolates. CONCLUSIONS:
      Augmenting our previously developed and published JCVI Primer Design Pipeline, we
      achieved similarly high sequencing success rates with only minor software
      modifications. The recommended methodology for the construction of the consensus
      sequence that encapsulates the allelic variation of the targeted population and
      is a key step prior to designing degenerate primers is also formally described.

PMID- 23131098
TI  - Military veterans with mental health problems: a protocol for a systematic review
      to identify whether they have an additional risk of contact with criminal justice
      systems compared with other veterans groups.
AB  - BACKGROUND: There is concern that some veterans of armed forces, in particular
      those with mental health, drug or alcohol problems, experience difficulty
      returning to a civilian way of life and may subsequently come into contact with
      criminal justice services and imprisonment. The aim of this review is to examine
      whether military veterans with mental health problems, including substance use,
      have an additional risk of contact with criminal justice systems when compared
      with veterans who do not have such problems. The review will also seek to
      identify veterans' views and experiences on their contact with criminal justice
      services, what contributed to or influenced their contact and whether there are
      any differences, including international and temporal, in incidence, contact
      type, veteran type, their presenting health needs and reported experiences.
      METHODS/DESIGN: In this review we will adopt a methodological model similar to
      that previously used by other researchers when reviewing intervention studies.
      The model, which we will use as a framework for conducting a review of
      observational and qualitative studies, consists of two parallel synthesis stages
      within the review process; one for quantitative research and the other for
      qualitative research. The third stage involves a cross study synthesis, enabling
      a deeper understanding of the results of the quantitative synthesis. A range of
      electronic databases, including MEDLINE, PsychINFO, CINAHL, will be
      systematically searched, from 1939 to present day, using a broad range of search
      terms that cover four key concepts: mental health, military veterans, substance
      misuse, and criminal justice. Studies will be screened against topic specific
      inclusion/exclusion criteria and then against a smaller subset of design specific
      inclusion/exclusion criteria. Data will be extracted for those studies that meet
      the inclusion criteria, and all eligible studies will be critically appraised.
      Included studies, both quantitative and qualitative, will then undergo stage
      specific analysis and synthesis. The final stage will combine the findings of
      both syntheses to enable new understandings of why, how, and by how much,
      military veterans with mental health problems, including problematic drug and
      alcohol use, come into contact with the criminal justice system.

PMID- 23131101
TI  - Development of a thermogravitational microcolumn with an interferometric
      contactless detection system.
AB  - We present a new type of thermogravitational (TG) column, a so-called TG
      microcolumn with transparent windows and a very small sample volume of less than
      50 MUL. The TG microcolumn has a planar geometry with a thickness of 0.523 +/-
      0.004 mm, a height of 30 mm, and a width of 3 mm. The concentration difference
      between two points at different heights is measured with an interferometer using
      active phase control. From the concentration difference we can determine the
      thermal diffusion coefficient, D(T), using the refractive index variation with
      concentration, which has to be determined independently. We studied the three
      binary mixtures of dodecane, isobutylbenzene, and 1,2,3,4-tetrahydronaphthalene
      with a concentration of 50 wt % at a temperature of 298 K. The thermal diffusion
      coefficients agree within a few percent with the proposed benchmark values. In
      addition we investigated also the binary mixture toluene/n-hexane and compare the
      results with literature values. For the investigated mixtures the typical
      measurement times were between 30 min and 2 h with an applied temperature
      difference of DeltaT = 6 K.

PMID- 23131100
TI  - Effects of alkoxy chain length in alkoxy-substituted dihydronaphthyl-based
      [60]fullerene bisadduct acceptors on their photovoltaic properties.
AB  - A series of alkoxy-substituted dihydronaphthyl-based [60]fullerene bisadduct
      derivatives (Cn-NCBA, n = 1-6), with the alkoxy chain length from 1 to 6 carbon
      atoms, were synthesized as acceptors for polymer solar cells (PSCs), for the
      purpose of systematically investigating the effects of fullerene derivative
      structures on the photovoltaic properties of PSCs. Although the absorption
      spectra and electrochemical properties of Cn-NCBA are almost the same, the PSCs
      based on P3HT:Cn-NCBA showed different photovoltaic properties. The device based
      on the P3HT:C3-NCBA blend demonstrated the highest power-conversion efficiency
      (PCE) of ca. 4.1%, while those with shorter or longer alkoxy-substituted
      dihydronaphthyl-based [60]fullerene bisadduct derivatives showed relatively lower
      PCE values. C5-NCBA and C6-NCBA with longer alkoxy chain length showed relatively
      low electron mobilities, leading to relatively poor photovoltaic performance.
      More importantly, we found that the alkoxy chain length changes the
      hydrophobicity of Cn-NCBA and, thus, the interfacial interaction and miscibility
      with P3HT, which were analyzed by interfacial tension and atomic force microscopy
      (AFM) measurements. The hydrophobicity of Cn-NCBA increased as the alkoxy chain
      length increased. A distinct phase separation for the P3HT:C1-NCBA blend film due
      to the large interfacial tension and poor miscibility between P3HT and C1-NCBA
      could be one reason for the low PCE value of the C1-NCBA-based devices. C3-NCBA
      may provide the most appropriate combination of electron mobility and miscibility
      with P3HT to achieve optimal photovoltaic properties. The current study provides
      the molecular structure-device performance relationship, especially with respect
      to the alkoxy chain length of Cn-NCBA and their interfacial interactions with
      P3HT, and suggests a design rule for high-performance fullerene bisadduct
      acceptors for PSC applications.

PMID- 23131103
TI  - Crystal structure control of zinc-blende CdSe/CdS core/shell nanocrystals:
      synthesis and structure-dependent optical properties.
AB  - Nearly monodisperse zinc-blende CdSe/CdS core/shell nanocrystals were synthesized
      by epitaxial growth of 1-6 monolayers of CdS shell onto presynthesized zinc
      blende CdSe core nanocrystals in one pot. To retain the zinc-blende structure,
      the reaction temperature was lowered to the 100-140  degrees C range by using
      cadmium diethyldithiocarbamate as a single-source precursor and primary amine as
      activation reagents for the precursor. Although the wurtzite counterparts grown
      under the same conditions showed optical properties similar to those reported in
      the literature, zinc-blende CdSe/CdS core/shell nanocrystals demonstrated
      surprisingly different optical properties, with ensemble single-exponential
      photoluminescence decay, significant decrease of photoluminescence peak width by
      the shell growth, and comparatively high photoluminescence quantum yields. The
      lifetime for the single-exponential ensemble photoluminescence decay of zinc
      blende CdSe/CdS core/shell nanocrystals with 3-4 monolayers of CdS shell was
      reproducibly found to be approximately 16.5 +/- 1.0 ns.

PMID- 23131104
TI  - Natural coniferous resin lacquer in treatment of toenail onychomycosis: an
      observational study.
AB  - In in vitro tests, natural coniferous resin from the Norway spruce (Picea abies)
      is strongly antifungal. In this observational study, we tested the clinical
      effectiveness of a lacquer composed of spruce resin for topical treatment of
      onychomycosis. Thirty-seven patients with clinical diagnosis of onychomycosis
      were enrolled into the study. All patients used topical resin lacquer treatment
      daily for 9 months. A mycological culture and potassium hydroxide (KOH) stain
      were done from nail samples in the beginning and in the end of the study.
      Treatment was considered effective, if a mycological culture was negative and
      there was an apparent clinical cure. At study entry, 20 patients (20/37; 54%; 95%
      CI: 38-70) had a positive mycological culture and/or positive KOH stain for
      dermatophytes. At study end, the result of 13 patients was negative (13/19; 68%;
      95% CI: 48-89). In one case (1/14; 7%; 95% CI: 0-21) the mycological culture was
      initially negative, but it turned positive during the study period. By 14
      compliant patients (14/32; 44%; 95% CI: 27-61), resin lacquer treatment was
      considered clinically effective: complete healing took place in three cases (9%)
      and partial healing in 11 cases (85%). The results indicate some evidence of
      clinical efficacy of the natural coniferous resin used for topical treatment of
      onychomycosis.

PMID- 23131105
TI  - Calcium and arrhythmias: ignore at your peril.

PMID- 23131106
TI  - Do we need another risk score protocol when the good old-fashioned method works
      better?

PMID- 23131107
TI  - Shock treatment: swimming pool contact dermatitis.
AB  - Allergic contact dermatitis to potassium peroxymonosulfate, used as a chemical
      shock treatment for hot tubs and swimming pools, should be in the differential
      diagnosis for patients presenting with dermatitis triggered by swimming pool or
      hot tub exposure. We report the first pediatric case of allergic contact
      dermatitis to potassium peroxymonosulfate after swimming exposure. 

PMID- 23131108
TI  - Adhesion and biologic behavior of human periodontal fibroblast cells to resin
      ionomer Geristore: a comparative analysis.
AB  - AIM: The resin ionomer Geristore, originally designed for restorative procedures,
      has been used extensively in treating subgingival defects (such as root
      resorption and perforations) and as a retrofilling material. The purpose of this
      study was to evaluate the cell adhesion as well as in vitro biocompatibility of
      human periodontal fibroblast cells with resin ionomer Geristore in comparison
      with mineral trioxide aggregate (MTA) and glass ionomer cement (GIC). MATERIAL
      AND METHOD: Adhesion, growth, and morphology of human periodontal fibroblasts
      over test materials were evaluated by scanning electron microscopy (SEM).
      Biocompatibility was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5
      diphenyltetrazolium bromide salt (MTT) assay. RESULTS: Compared to glass
      coverslips, cells grew and spread qualitatively better over the surface of
      Geristore in comparison with the other test materials. In vitro interpretation
      indicates that Geristore is significantly less cytotoxic to human periodontal
      ligament cells. Results of statistical analysis revealed that material extracts
      had significant effect on cell proliferation at both 24 h (F = 547.62, P < 0.05)
      and at 48 h (F = 6048.18, P < 0.05). CONCLUSION: Our study supports that
      Geristore has enhanced biologic behavior to human periodontal ligament cells and
      superior biocompatibility in comparison with MTA and GIC, so it can be suggested
      as a material of choice in root resorption, perforations, and root-end filling.

PMID- 23131109
TI  - Modeling variably saturated multispecies reactive groundwater solute transport
      with MODFLOW-UZF and RT3D.
AB  - A numerical model was developed that is capable of simulating multispecies
      reactive solute transport in variably saturated porous media. This model consists
      of a modified version of the reactive transport model RT3D (Reactive Transport in
      3 Dimensions) that is linked to the Unsaturated-Zone Flow (UZF1) package and
      MODFLOW. Referred to as UZF-RT3D, the model is tested against published
      analytical benchmarks as well as other published contaminant transport models,
      including HYDRUS-1D, VS2DT, and SUTRA, and the coupled flow and transport
      modeling system of CATHY and TRAN3D. Comparisons in one-dimensional, two
      dimensional, and three-dimensional variably saturated systems are explored. While
      several test cases are included to verify the correct implementation of variably
      saturated transport in UZF-RT3D, other cases are included to demonstrate the
      usefulness of the code in terms of model run-time and handling the reaction
      kinetics of multiple interacting species in variably saturated subsurface
      systems. As UZF1 relies on a kinematic-wave approximation for unsaturated flow
      that neglects the diffusive terms in Richards equation, UZF-RT3D can be used for
      large-scale aquifer systems for which the UZF1 formulation is reasonable, that
      is, capillary-pressure gradients can be neglected and soil parameters can be
      treated as homogeneous. Decreased model run-time and the ability to include site
      specific chemical species and chemical reactions make UZF-RT3D an attractive
      model for efficient simulation of multispecies reactive transport in variably
      saturated large-scale subsurface systems. 

PMID- 23131110
TI  - Antioxidant and quinone reductase-inducing constituents of black chokeberry
      (Aronia melanocarpa) fruits.
AB  - Using in vitro hydroxyl radical-scavenging and quinone reductase-inducing assays,
      bioactivity-guided fractionation of an ethyl acetate-soluble extract of the
      fruits of the botanical dietary supplement, black chokeberry (Aronia
      melanocarpa), led to the isolation of 27 compounds, including a new depside,
      ethyl 2-[(3,4-dihydroxybenzoyloxy)-4,6-dihydroxyphenyl] acetate (1), along with
      26 known compounds (2-27). The structures of the isolated compounds were
      identified by analysis of their physical and spectroscopic data ([alpha](D), NMR,
      IR, UV, and MS). Altogether, 17 compounds (1-4, 9, 15-17, and 19-27) showed
      significant antioxidant activity in the hydroxyl radical-scavenging assay, with
      hyperin (24, ED(50) = 0.17 MUM) being the most potent. The new compound (1,
      ED(50) = 0.44 MUM) also exhibited potent antioxidant activity in this assay.
      Three constituents of black chokeberry fruits doubled quinone reductase activity
      at concentrations <20 MUM, namely, protocatechuic acid [9, concentration required
      to double quinone reductase activity (CD) = 4.3 MUM], neochlorogenic acid methyl
      ester (22, CD = 6.7 MUM), and quercetin (23, CD = 3.1 MUM).

PMID- 23131112
TI  - Importance of secondary interactions in twisted doubly hydrogen bonded complexes.
AB  - Three model hydrogen bond arrays that form complexes with large twist angles
      between their heterocyclic rings were synthesized differing only in the sequence
      of their hydrogen bond donors and acceptors. The complementary and self
      complementary association of the arrays to form complexes was studied
      computationally and in solution. The analysis reveals the significant impact
      secondary interactions have on complex stability in such an arrangement despite
      the very different topology in comparison to typical planar arrays.

PMID- 23131113
TI  - Differences in nuclearity, molecular shapes, and coordination modes of azide in
      the complexes of Cd(II) and Hg(II) with a "metalloligand" [CuL] (H2L = N,N'
      bis(salicylidene)-1,3-propanediamine): characterization in solid and in
      solutions, and theoretical calculations.
AB  - Two new heterometallic copper(II)-mercury(II) complexes [(CuL)Hg(N3)2]n (1) and
      [(CuL)2Hg(N3)2] (2) and one copper(II)-cadmium(II) complex [(CuL)2Cd(N3)2] (3)
      have been synthesized using "metalloligand" [CuL] (where H2L = N,N'
      bis(salicylidene)-1,3-propanediamine) and structurally characterized. Complex 1
      is a one-dimensional (1D) helical coordination polymer constructed by the joining
      of the dinuclear [(CuL)Hg(N3)2] units through a single MU-l,l azido bridge. In
      the dinuclear unit the Hg(II) is bonded with two phenoxido oxygen atoms of
      "metalloligand" [CuL] and two nitrogen atoms of azido ligands. Complex 2 is a
      linear trinuclear entity, in which two terminal "metalloligands" [CuL] are
      coordinated to central Hg(II) through double phenoxido bridges. The azido ligands
      link the central mercury atom with the terminal copper atoms via MU-l,3 bridges.
      In contrast, the trinuclear complex 3 is bent. Here, in addition to two double
      phenoxido bridges, central Cd(II) is bonded to two mutually cis nitrogen atoms of
      two terminal azido ligands. The variation in the coordination modes of the azido
      ligand seems to be responsible for the different molecular shapes of 2 and 3.
      Interestingly, bond distances between the Hg atoms and the central nitrogen atom
      of the azido ligands are 2.790(4) and 2.816(5) A in 1 and 2.823(4) A in 2. These
      bond distances are significantly less than the sum of van der Waals radii of
      mercury (2.04 A) and nitrogen (1.55 A) and considerably longer than the sum of
      their covalent radii (2.03 A). However the distances are similar to reported Hg-N
      bond distances of some Hg(II) complexes. Therefore, we have performed a
      theoretical density functional theory study to know whether there is any
      interaction between the central nitrogen atom of the azido ligand and the mercury
      atoms. We have used the Bader's "atoms-in-molecules", energetic and orbital
      analyses to conclude that such interaction does not exist. The probable reason
      for different molecular shapes observed in trinuclear complexes of 2 and 3 also
      has been studied and explained by theoretical calculations and using the CSD.
      Electronic spectra, EPR spectra and ESI mass spectra show that all three
      complexes lose their solid state identity in solution. 

PMID- 23131111
TI  - Cellular alterations in human traumatic brain injury: changes in mitochondrial
      morphology reflect regional levels of injury severity.
AB  - Mitochondrial dysfunction may be central to the pathophysiology of traumatic
      brain injury (TBI) and often can be recognized cytologically by changes in
      mitochondrial ultrastructure. This study is the first to broadly characterize and
      quantify mitochondrial morphologic alterations in surgically resected human TBI
      tissues from three contiguous cortical injury zones. These zones were designated
      as injury center (Near), periphery (Far), and Penumbra. Tissues from 22 patients
      with TBI with varying degrees of damage and time intervals from TBI to surgical
      tissue collection within the first week post-injury were rapidly fixed in the
      surgical suite and processed for electron microscopy. A large number of
      mitochondrial structural patterns were identified and divided into four survival
      categories: normal, normal reactive, reactive degenerating, and end-stage
      degenerating profiles. A tissue sample acquired at 38 hours post-injury was
      selected for detailed mitochondrial quantification, because it best exhibited the
      wide variation in cellular and mitochondrial changes consistently noted in all
      the other cases. The distribution of mitochondrial morphologic phenotypes varied
      significantly between the three injury zones and when compared with control
      cortical tissue obtained from an epilepsy lobectomy. This study is unique in its
      comparative quantification of the mitochondrial ultrastructural alterations at
      progressive distances from the center of injury in surviving TBI patients and in
      relation to control human cortex. These quantitative observations may be useful
      in guiding the translation of mitochondrial-based neuroprotective interventions
      to clinical implementation.

PMID- 23131114
TI  - Health-related quality of life in adolescent chronotypes--a model for the effects
      of sleep problems, sleep-related cognitions, and self-efficacy.
AB  - In adolescence, the circadian preference shifts toward eveningness orientation.
      Eveningness seems to be negatively correlated with quality of life. The present
      study investigates influencing factors of this association and proposes a model
      for the mediating effects of sleep, sleep-related cognitions, and self-efficacy
      according to chronotype. The sample comprised N = 280 adolescents (172 girls)
      aged 14-16 yrs (mean = 15.19, SD = .76). Circadian preference, health-related
      quality of life (HRQoL), sleep disturbances, sleep-related dysfunctional
      cognitions, and general perceived self-efficacy were assessed online. Morning
      orientated adolescents reported significantly higher HRQoL and less insomnia
      symptoms compared with evening-oriented chronotypes. In the total sample,
      insomnia symptoms mediated the relationship of chronotype and HRQoL. The
      strongest predictor of HRQoL in evening types was the degree of sleep-related
      dysfunctional cognitions. HRQoL in morning types was most strongly predicted by
      general self-efficacy, i.e., the global confidence in coping abilities. The
      findings support a negative relationship of eveningness and HRQoL in adolescents.
      Insomnia symptoms were identified to be mediating factors in this relationship.
      The influence of the mediating factors on HRQoL differed between morning and
      evening types. The model provides implications of how to enhance HRQoL in
      adolescents according to their circadian preference.

PMID- 23131115
TI  - Teaching of evidence-based medicine to medical students in Mexico: a randomized
      controlled trial.
AB  - BACKGROUND: Evidence-Based Medicine (EBM) is an important competency for the
      healthcare professional. Experimental evidence of EBM educational interventions
      from rigorous research studies is limited. The main objective of this study was
      to assess EBM learning (knowledge, attitudes and self-reported skills) in
      undergraduate medical students with a randomized controlled trial. METHODS: The
      educational intervention was a one-semester EBM course in the 5th year of a
      public medical school in Mexico. The study design was an experimental parallel
      group randomized controlled trial for the main outcome measures in the 5th year
      class (M5 EBM vs. M5 non-EBM groups), and quasi-experimental with static-groups
      comparisons for the 4th year (M4, not yet exposed) and 6th year (M6, exposed 6
      months to a year earlier) groups. EBM attitudes, knowledge and self-reported
      skills were measured using Taylor's questionnaire and a summative exam which
      comprised of a 100-item multiple-choice question (MCQ) test. RESULTS: 289 Medical
      students were assessed: M5 EBM=48, M5 non-EBM=47, M4=87, and M6=107. There was a
      higher reported use of the Cochrane Library and secondary journals in the
      intervention group (M5 vs. M5 non-EBM). Critical appraisal skills and attitude
      scores were higher in the intervention group (M5) and in the group of students
      exposed to EBM instruction during the previous year (M6). The knowledge level was
      higher after the intervention in the M5 EBM group compared to the M5 non-EBM
      group (p<0.001, Cohen's d=0.88 with Taylor's instrument and 3.54 with the 100
      item MCQ test). M6 Students that received the intervention in the previous year
      had a knowledge score higher than the M4 and M5 non-EBM groups, but lower than
      the M5 EBM group. CONCLUSIONS: Formal medical student training in EBM produced
      higher scores in attitudes, knowledge and self-reported critical appraisal skills
      compared with a randomized control group. Data from the concurrent groups add
      validity evidence to the study, but rigorous follow-up needs to be done to
      document retention of EBM abilities.

PMID- 23131116
TI  - Diabetes risk perception in women with recent gestational diabetes: delivery to
      the postpartum visit.
AB  - OBJECTIVE: Low perceived risk for type 2 diabetes (T2DM) may be a barrier to
      lifestyle change in women with recent gestational diabetes (GDM). We assessed
      perceived risk for T2DM at delivery and postpartum. METHODS: We used a validated
      diabetes risk perception instrument to survey women with GDM at delivery and
      postpartum. We compared women with low perceived risk for T2DM at delivery to
      those with high perceived risk. RESULTS: The majority (N = 43 of 70, 61%)
      perceived high risk at delivery. Women who perceived low risk were younger (30.7
      +/- 6.3 versus 35.0 +/- 4.5 years, p = 0.003) than women who perceived high risk.
      Although knowledge of risk factors for T2DM was poor (mean 6.0 +/- 1.9, of 11
      points), 95% correctly identified GDM as a risk factor. Perceived risk was
      maintained in most (N = 51 of 58, 88%) who returned for their postpartum visit.
      Low perceived risk was not associated with loss to follow up, however correct
      identification of GDM as a risk factor was protective (OR 0.05, 95% CI 0.005,
      0.56). CONCLUSIONS: Risk perception is accurate in most women with GDM at
      delivery and postpartum. Further study is needed to translate perceived risk into
      preventive behaviors in women with recent GDM.

PMID- 23131117
TI  - Going back to the future with Guthrie-powered epigenome-wide association studies.
AB  - Epigenome-wide association studies (EWAS) can be used to investigate links
      between early life environment, epigenetics and disease. However, such studies
      raise the question of which came first: the mark or the malady? A recent study
      has demonstrated that EWAS can be performed on neonatal 'Guthrie' heel-prick
      blood spots. As Guthrie cards are collected from all newborn infants and stored
      indefinitely in many countries, they represent an important timepoint to compare
      with later disease-associated epigenetic marks. 

PMID- 23131118
TI  - Synthesis of one-dimensional CdS@TiO2 core-shell nanocomposites photocatalyst for
      selective redox: the dual role of TiO2 shell.
AB  - One-dimensional (1D) CdS@TiO2 core-shell nanocomposites (CSNs) have been
      successfully synthesized via a two-step solvothermal method. The structure and
      properties of 1D CdS@TiO2 core-shell nanocomposites (CdS@TiO2 CSNs) have been
      characterized by a series of techniques, including X-ray diffraction (XRD),
      ultraviolet-visible-light (UV-vis) diffuse reflectance spectra (DRS), field
      emission scanning electron microscopy (FESEM), photoluminescence spectra (PL),
      and electron spin resonance (ESR) spectroscopy. The results demonstrate that 1D
      core-shell structure is formed by coating TiO2 onto the substrate of CdS
      nanowires (NWs). The visible-light-driven photocatalytic activities of the as
      prepared 1D CdS@TiO2 CSNs are evaluated by selective oxidation of alcohols to
      aldehydes under mild conditions. Compared to bare CdS NWs, an obvious enhancement
      of both conversion and yield is achieved over 1D CdS@TiO2 CSNs, which is ascribed
      to the prolonged lifetime of photogenerated charge carriers over 1D CdS@TiO2 CSNs
      under visible-light irradiation. Furthermore, it is disclosed that the
      photogenerated holes from CdS core can be stuck by the TiO2 shell, as evidenced
      by controlled radical scavenger experiments and efficiently selective reduction
      of heavy-metal ions, Cr(VI), over 1D CdS@TiO2 CSNs, which consequently leads to
      the fact that the reaction mechanism of photocatalytic oxidation of alcohols over
      1D CdS@TiO2 CSNs is apparently different from that over 1D CdS NWs under visible
      light irradiation. It is hoped that our work could not only offer useful
      information on the fabrication of various specific 1D core-shell nanostructures,
      but also open a new doorway of such 1D core-shell semiconductors as visible-light
      photocatalysts in the promising field of selective transformations.

PMID- 23131119
TI  - The use of schoolbags and musculoskeletal symptoms among primary school children:
      are the recommended weight limits adequate?
AB  - This cross-sectional study investigated the use of schoolbags and the prevalence
      of musculoskeletal symptoms among a sample of 307 Iranian primary school children
      aged 7-12 years. The average load carried by the children was 2.9 kg
      (representing on average 10.1% of the child's body weight). Most children chose
      to carry the schoolbag across two shoulders, although significant numbers also
      carried it on one shoulder or in the hand. Although the amount of load carried by
      school children was within the currently suggested load limit of 10% to 15% of
      the child's body weight, the prevalence of musculoskeletal problems was very high
      among the study population. Multiple logistic regression models indicated that
      the method of carrying the schoolbag was significantly associated with hand/wrist
      and shoulder symptoms, and that the time spent carrying a schoolbag was
      associated with hand/wrist and upper back symptoms. Schoolbag weight (expressed
      as a percentage of body weight) was only associated with hand/wrist symptoms. The
      results suggest that the current recommended weight limit may not be appropriate
      for school children in primary school, and that guidelines ought to consider
      factors other than relative schoolbag weight that influence the use of schoolbags
      among this age group. PRACTITIONER SUMMARY: The carrying of schoolbags by primary
      school children and their musculoskeletal symptoms were investigated. The results
      provide evidence that the current weight limit may not be appropriate for younger
      school children, and that such guidelines should consider a broader combination
      of the factors that influence the use of schoolbags.

PMID- 23131120
TI  - Solitary neurolymphomatosis of the brachial plexus mimicking benign nerve sheath
      tumour: case report.
AB  - Neurolymphomatosis typically appears as a diffuse lesion with thickening of the
      affected nerves on magnetic resonance imaging (MRI). MRI in the present case
      revealed a well-defined, solitary lesion showing continuity with brachial plexus
      nerves. Findings including clinical symptoms resembled benign nerve sheath tumour
      rather than neurolymphomatosis. Intra-operatively, the C8 root was focally
      swollen, corresponding to a well-circumscribed lesion on MRI. The diagnosis of
      neurolymphomatosis was obtained only after resection biopsy. Post-operatively,
      (18)F-fluorodeoxyglucose positron emission tomography proved useful for follow-up
      evaluation. We offer the first description of the MRI characteristics of brachial
      plexopathy in neurolymphomatosis, along with the clinical course.

PMID- 23131121
TI  - Triheptanoin supplementation to ketogenic diet curbs cognitive impairment in
      APP/PS1 mice used as a model of familial Alzheimer's disease.
AB  - Diets containing a high proportion of fat with respect to protein plus
      carbohydrates are capable of inducing ketone body production in the liver, which
      provides an energetic alternative to glucose. Some ketogenic diets have been
      tested as therapeutic strategies for treating metabolic disorders related to a
      deficiency in glucose-driven ATP generation. However, ketone bodies are not
      capable of providing extra tricarboxylic acid cycle intermediates, limiting the
      anabolic capacity of the cell. Therefore, it is reasonable to hypothesize that
      supplementing a ketogenic diet with anaplerotic compounds such as triheptanoin
      may improve ketogenic diet effectiveness. The present study tests this hypothesis
      in APP/PS1 (APPswe/PS1dE9) transgenic mice, used as a model of familial
      Alzheimer's disease because impaired energy supply to neurons has been linked to
      this neurodegenerative process. Triheptanoin supplementation to a ketogenic diet
      for three months and starting at the age of three months reduces the memory
      impairment of APP/PS1 mice at the age of 6 months. The Abeta production and
      deposition were not significantly altered by the ketogenic diet, supplemented or
      not by triheptanoin. However, mice fed with triheptanoin-rich ketogenic diet have
      shown decreased astroglial response in the vicinity of Abeta plaques and
      decreased expression of the pro-inflammatory cytokine interferon-gamma in
      astrocytes. These findings correlate with transcriptional up-regulation of the
      ROS detoxifying mechanisms Sirt1 and Pparg, thus linking triheptanoin with
      improved mitochondrial status. Present findings support the concept that
      ketogenic diets supplemented with anaplerotic compounds can be considered
      potential therapeutic strategies at early stages of Alzheimer's disease.

PMID- 23131122
TI  - Suzuki-Miyaura cross-coupling of potassium alkoxyethyltrifluoroborates: access to
      aryl/heteroarylethyloxy motifs.
AB  - The introduction of an alkoxyethyl moiety onto aromatic substructures has
      remained a long-standing challenge for synthetic organic chemists. The main
      reasons are the inherent instability of alkoxyethylmetallic species and the lack
      of general procedures to access them. A new method utilizing a cross-coupling
      strategy based on the exceptional properties of organotrifluoroborates has been
      developed, and the method allows an easy and efficient installation of this unit
      on a broad range of aryl and heteroaryl bromides.

PMID- 23131124
TI  - The unwound portion dividing helix IV of NhaA undergoes a conformational change
      at physiological pH and lines the cation passage.
AB  - pH and Na(+) homeostasis in all cells requires Na(+)/H(+) antiporters. The
      crystal structure of NhaA, the main antiporter of Escherichia coli, has provided
      general insights into antiporter mechanisms and their pH regulation. Functional
      studies of NhaA in the membrane have yielded valuable information regarding its
      functionality in situ at physiological pH. Here, we Cys-scanned the discontinuous
      transmembrane segment (TM) IV (helices IVp and IVc connected by an extended
      chain) of NhaA to explore its functionality at physiological pH. We then tested
      the accessibility of the Cys replacements to the positively charged SH reagent [2
      (trimethylammonium)ethyl] methanethiosulfonate bromide (MTSET) and the negatively
      charged 2-sulfonatoethyl methanethiosulfonate (MTSES) in intact cells at pH 8.5
      and 6.5 and in parallel tested their accessibility to MTSET in high-pressure
      membranes at both pH values. We found that the outer membrane of E. coli TA16
      acts as a partially permeable barrier to MTSET. Overcoming this technical
      problem, we revealed that (a) Cys replacement of the most conserved residues of
      TM IV strongly increases the apparent K(m) of NhaA to both Na(+) and Li(+), (b)
      the cationic passage of NhaA at physiological pH is lined by the most conserved
      and functionally important residues of TM IV, and (c) a pH shift from 6.5 to 8.5
      induces conformational changes in helix IVp and in the extended chain at
      physiological pH.

PMID- 23131123
TI  - A review of methods for detect human Papillomavirus infection.
AB  - Human Papillomavirus (HPV) is the most common sexually transmitted virus.
      Worldwide, the most common high-risk (HR)-HPV are -16/18, and approximately 70%
      of cervical cancers (CC) are due to infection by these genotypes. Persistent
      infection by HR-HPV is a necessary but not sufficient cause of this cancer, which
      develops over a long period through precursor lesions, which can be detected by
      cytological screening. Although this screening has decreased the incidence of CC,
      HPV-related cervical disease, including premalignant and malignant lesions,
      continues to be a major burden on health-care systems. Although not completely
      elucidated, the HPV-driven molecular mechanisms underlying the development of
      cervical lesions have provided a number of potential biomarkers for both
      diagnostic and prognostic use in the clinical management of women with HPV
      related cervical disease, and these biomarkers can also be used to increase the
      positive predictive value of current screening methods. In addition, they can
      provide insights into the biology of HPV-induced cancer and thus lead to the
      development of nonsurgical therapies. Considering the importance of detecting HPV
      and related biomarkers, a variety of methods are being developed for these
      purposes. This review summarizes current knowledge of detection methods for HPV,
      and related biomarkers that can be used to discriminate lesions with a high risk
      of progression to CC.

PMID- 23131125
TI  - Highly effective surface passivation of PbSe quantum dots through reaction with
      molecular chlorine.
AB  - PbSe nanocrystal quantum dots (NQDs) are a promising active material for a range
      of optoelectronic devices, including solar cells, high-sensitivity infrared (IR)
      photodetectors, and IR-emitting diodes and lasers. However, device realization
      has been constrained by these NQDs' chemical instability toward oxidation, which
      leads to uncontrollable changes in optical and electronic properties. Here, we
      present a simple method to enhance the stability of PbSe NQDs against oxidation
      and to improve their optical properties through reaction with molecular chlorine.
      The chlorine molecules preferentially etch out surface Se ions and react with Pb
      ions to form a thin (1-2 monolayers) PbCl(x) passivation layer which effectively
      prevents oxidation during long-term air exposure while passivating surface trap
      states to increase photoluminescence efficiency and decrease photocharging. Our
      method is simple, widely applicable to PbSe and PbS NQDs of a range of sizes,
      compatible with solution-based processes for fabricating NQD-based devices, and
      effective both in solution and in solid NQD films; thus, it is a practical
      protocol for facilitating advances over the full range of optoelectronic
      applications.

PMID- 23131126
TI  - Diversity and extracellular enzymatic activities of yeasts isolated from King
      George Island, the sub-Antarctic region.
AB  - BACKGROUND: Antarctica has been successfully colonized by microorganisms despite
      presenting adverse conditions for life such as low temperatures, high solar
      radiation, low nutrient availability and dryness. Although these "cold-loving"
      microorganisms are recognized as primarily responsible for nutrient and organic
      matter recycling/mineralization, the yeasts, in particular, remain poorly
      characterized and understood. The aim of this work was to study the yeast
      microbiota in soil and water samples collected on King George Island. RESULTS: A
      high number of yeast isolates was obtained from 34 soil and 14 water samples.
      Molecular analyses based on rDNA sequences revealed 22 yeast species belonging to
      12 genera, with Mrakia and Cryptococcus genera containing the highest species
      diversity. The species Sporidiobolus salmonicolor was by far the most ubiquitous,
      being identified in 24 isolates from 13 different samples. Most of the yeasts
      were psychrotolerant and ranged widely in their ability to assimilate carbon
      sources (consuming from 1 to 27 of the 29 carbon sources tested). All species
      displayed at least 1 of the 8 extracellular enzyme activities tested. Lipase,
      amylase and esterase activity dominated, while chitinase and xylanase were less
      common. Two yeasts identified as Leuconeurospora sp. and Dioszegia fristingensis
      displayed 6 enzyme activities. CONCLUSIONS: A high diversity of yeasts was
      isolated in this work including undescribed species and species not previously
      isolated from the Antarctic region, including Wickerhamomyces anomalus, which has
      not been isolated from cold regions in general. The diversity of extracellular
      enzyme activities, and hence the variety of compounds that the yeasts may degrade
      or transform, suggests an important nutrient recycling role of microorganisms in
      this region. These yeasts are of potential use in industrial applications
      requiring high enzyme activities at low temperatures.

PMID- 23131127
TI  - Pre- and post-partum mild underfeeding influences gene expression in the
      reproductive tract of cyclic dairy cows.
AB  - Undernutrition before and after calving has a detrimental effect on the fertility
      of dairy cows. The effect of nutritional stress was previously reported to
      influence gene expression in key tissues for metabolic health and reproduction
      such as the liver and the genital tract early after calving, but not at breeding,
      that is, between 70 and 90 days post-partum. This study investigated the effects
      of pre- and post-partum mild underfeeding on global gene expression in the
      oviduct, endometrium and corpus luteum of eight multiparous Holstein cows during
      the early and middle phases of an induced cycle 80 days post-partum. Four control
      cows received 100% of energy and protein requirements during the dry period and
      after calving, while four underfed received 80% of control diet. Oestrous
      synchronization treatment was used to induce ovulation on D80 post-partum.
      Oviducts, ovaries and the anterior part of each uterine horn were recovered
      surgically 4, 8, 12 and 15 days after ovulation. Corpora lutea were dissected
      from the ovaries, and the endometrium was separated from the stroma and
      myometrium in each uterine horn. The oviduct segments were comprised of ampulla
      and isthmus. RNAs from ipsi- and contralateral samples were pooled on an equal
      weight basis. In each tissue, gene expression was assessed on a custom bovine 10K
      array. No differentially expressed gene (DEG) in the corpus luteum was identified
      between underfed and control, conversely to 293 DEGs in the oviduct vs 1 in the
      endometrium under a false discovery rate (FDR) < 0.10 and 1370 DEGs vs 3,
      respectively, under FDR < 0.15. Additionally, we used dedicated statistics
      (regularized canonical correlation analysis) to correlate the post-partum
      patterns of six plasma metabolites and hormones related to energy metabolism
      measured weekly between calving and D80 with gene expression. High correlations
      were observed between post-partum patterns of IGF-1, insulin, beta
      hydroxybutyrate and the expression in the oviduct of genes related to
      reproductive system disease, connective tissue disorders and metabolic disease.
      Moreover, we found special interest in the literature to retinoic acid-related
      genes (e.g. FABP5/CRABP2) that might indicate abnormalities in post-partum tissue
      repair mechanisms. In conclusion, this experiment highlights relationships
      between underfeeding and gene expression in the oviduct and endometrium after
      ovulation in cyclic Holstein cows. This might help to explain the effect of mild
      undernutrition on fertilization failure and early embryonic mortality in post
      partum dairy cows.

PMID- 23131128
TI  - Stem cell models of Alzheimer's disease and related neurological disorders.
AB  - Human models of Alzheimer's disease (AD) have the potential to complement
      existing animal models for carrying out functional studies of AD pathogenesis and
      the development of novel therapies. An effective human cellular model of AD would
      use the appropriate cell types and ideally neural circuits affected by the
      disease, would develop relevant pathology and would do so in a reproducible
      manner over a timescale short enough for practical use. A pressing question for
      the usefulness of this approach is whether neurological diseases that take
      decades to become manifest in humans can be successfully modelled over a
      reasonable timescale. We discuss here whether these models can do more than
      simply replicate what is already known about AD, and evaluate some of their
      potentially unique advantages. 

PMID- 23131129
TI  - Comparison of segmented flow analysis and ion chromatography for the quantitative
      characterization of carbohydrates in tobacco products.
AB  - Segmented flow analysis (SFA) and ion chromatography with pulsed amperometric
      detection (IC-PAD) are widely used analytical techniques for the analysis of
      glucose, fructose, and sucrose in tobacco. In the work presented here, 27 cured
      tobacco leaves and 21 tobacco products were analyzed for sugars using SFA and IC.
      The results of these analyses demonstrated that both techniques identified the
      same trends in sugar content across tobacco leaf and tobacco product types.
      However, comparison of results between techniques was limited by the selectivity
      of the SFA method, which relies on the specificity of the reaction of p
      hydroxybenzoic acid hydrazide (PAHBAH) with glucose and fructose to generate a
      detectable derivative. Sugar amines and chlorogenic acid, which are found in
      tobacco, are also known to react with PAHBAH to form a reaction product that
      interferes with the analysis of fructose and glucose. To mitigate this problem,
      solid phase extraction (SPE) was used to remove interferences such as sugar
      amines and chlorogenic acid from sample matrices prior to SFA. A combination of
      C18 and cation exchange solid phase extraction cartridges was used, and the
      results from SFA and IC analyses showed significant convergence in the results of
      both analytical methods. For example, the average difference between the results
      from the SFA and IC analyses for flue-cured tobacco samples dropped by 73% when
      the two-step C18/cation exchange resin sample cleanup was used.

PMID- 23131130
TI  - Temporal trends in mucocutaneous findings among human immunodeficiency virus 1
      infected children in a population-based cohort.
AB  - The objective of the study was to determine the prevalence of pediatric human
      immunodeficiency virus 1 (HIV-1) mucocutaneous manifestations in the era of
      highly active antiretroviral therapy (HAART). We conducted population-based,
      prospective, multicenter pediatric HIV-1 surveillance in 276 children with
      perinatally acquired HIV-1 from 1988 to 2009. Centers for Disease Control and
      Prevention (CDC)-defined HIV-1 related mucocutaneous conditions among the 276
      children were: category A (n = 152), B (n = 60), and C (n = 1). Nearly half of
      the category A and B diagnoses (43.4% [66/152] and 35.0% [21/60], respectively)
      occurred in the first year of life, with 59.2% (90/152) and 61.7% (37/60),
      respectively, occurring in the first 2 years of life. The most frequent
      infectious diagnosis was oropharyngeal thrush (n = 117, 42.4%); the most common
      inflammatory diagnosis was diaper dermatitis (n = 71, 25.7%). There was a
      temporal decline in the prevalence of A (pre-HAART cohort, 123; post-HAART
      cohort, 29; p < 0.01) and B (pre-HAART, 55; post-HAART, 5; p < 0.01)
      mucocutaneous diagnoses. In children with perinatal HIV-1, there was a
      significant decline in CDC category A and B mucocutaneous diagnoses by temporal
      cohort, consistent with the introduction of antiretroviral medications and HAART.
      Clinical category A and B mucocutaneous diagnoses were most common in the first 2
      years of life, emphasizing the importance of early HIV-1 testing and HAART
      initiation.

PMID- 23131132
TI  - Recent developmental findings relevant to the clinical significance of the
      myocardial venous sleeves.

PMID- 23131131
TI  - Analyses of a Glycine max degradome library identify microRNA targets and
      microRNAs that trigger secondary siRNA biogenesis.
AB  - Plant microRNAs (miRNAs) regulate gene expression mainly by guiding cleavage of
      target mRNAs. In this study, a degradome library constructed from different
      soybean (Glycine max (L.) Merr.) tissues was deep-sequenced. 428 potential
      targets of small interfering RNAs and 25 novel miRNA families were identified. A
      total of 211 potential miRNA targets, including 174 conserved miRNA targets and
      37 soybean-specific miRNA targets, were identified. Among them, 121 targets were
      first discovered in soybean. The signature distribution of soybean primary miRNAs
      (pri-miRNAs) showed that most pri-miRNAs had the characteristic pattern of Dicer
      processing. The biogenesis of TAS3 small interfering RNAs (siRNAs) was conserved
      in soybean, and nine Auxin Response Factors were identified as TAS3 siRNA
      targets. Twenty-three miRNA targets produced secondary small interfering RNAs
      (siRNAs) in soybean. These targets were guided by five miRNAs: gma-miR393, gma
      miR1508, gma-miR1510, gma-miR1514, and novel-11. Multiple targets of these
      secondary siRNAs were detected. These 23 miRNA targets may be the putative novel
      TAS genes in soybean. Global identification of miRNA targets and potential novel
      TAS genes will contribute to research on the functions of miRNAs in soybean.

PMID- 23131134
TI  - The subcutaneous ICD: a niche indication or the next contender of the transvenous
      ICD?

PMID- 23131133
TI  - Effect of Er,Cr:YSGG laser, air abrasion, and silane application on repaired
      shear bond strength of composites.
AB  - Aged resin composites have a limited number of carbon-carbon double bonds to
      adhere to a new layer of resin. Study objectives were to 1) evaluate various
      surface treatments on repaired shear bond strength between aged and new resin
      composites and 2) to assess the influence of a silane coupling agent after
      surface treatments. METHODS: Eighty disk-shape resin composite specimens were
      fabricated and thermocycled 5000 times prior to surface treatment. Specimens were
      randomly assigned to one of the three surface treatment groups (n=20): 1) air
      abrasion with 50-MUm aluminum oxide, 2) tribochemical silica coating (CoJet), or
      3) Er,Cr:YSGG (erbium, chromium: yttrium-scandium-gallium-garnet) laser or to a
      no-treatment control group (n=20). Specimens were etched with 35% phosphoric
      acid, rinsed, and dried. Each group was divided into two subgroups (n=10): A) no
      silanization and B) with silanization. The adhesive agent was applied and new
      resin composite was bonded to each conditioned surface. Shear bond strength was
      evaluated and data analyzed using two-way analysis of variance (ANOVA). RESULTS:
      Air abrasion with 50-MUm aluminum oxide showed significantly higher repair bond
      strength than the Er,Cr:YSGG laser and control groups. Air abrasion with 50-MUm
      aluminum oxide was not significantly different from tribochemical silica coating.
      Tribochemical silica coating had significantly higher repair bond strength than
      Er,Cr:YSGG laser and the control. Er,Cr:YSGG laser and the control did not have
      significantly different repair bond strengths. Silanization had no influence on
      repair bond strength for any of the surface treatment methods. CONCLUSION: Air
      abrasion with 50-MUm aluminum oxide and tribochemical silica followed by the
      application of bonding agent provided the highest repair shear bond strength
      values, suggesting that they might be adequate methods to improve the quality of
      repairs of resin composites.

PMID- 23131135
TI  - Capillarisin inhibits iNOS, COX-2 expression, and proinflammatory cytokines in
      LPS-induced RAW 264.7 macrophages via the suppression of ERK, JNK, and NF-kappaB
      activation.
AB  - The aerial parts of Artemisia capillaris (Compositae) have been used in
      traditional Korean medicine as a cholagogic, antipyretic, anti-inflammatory, and
      diuretic purposes. In our previous study, ethanolic extracts of the plant
      demonstrated a marked anti-inflammatory effect in lipopolysaccharide (LPS)
      stimulated RAW 264.7 cells (J. Korean Soc. Appl. Biol. Chem., 2010, 53, 275-282).
      In the present study, capillarisin (CPS), a flavone, main constituent of A.
      capillaris, was examined for its anti-inflammatory activity in the cells. We
      found that CPS highly suppressed LPS-induced nitric oxide (NO) without exerting
      cytotoxic effects on RAW 264.7 cells. CPS inhibited the expression of LPS-induced
      inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein and
      their mRNA in a dose-dependent manner. Also, tumor necrosis factor (TNF)-alpha,
      interleukin (IL)-6, IL-1beta, and prostaglandin E(2) (PGE(2)) secretion were
      decreased by CPS in LPS-stimulated macrophages. As a result, CPS inhibited
      proinflammatory cytokines, iNOS, and COX-2, which is attributed to the
      suppression of LPS-induced ERK, JNK, and nuclear factor-kappaB (NF-kappaB)
      activation. Therefore, we demonstrate here that CPS potentially inhibits the
      biomarkers related to inflammation through the abrogation of ERK, JNK, and NF
      kappaB p65 activation, and it may be a potential therapeutic candidate for the
      treatment of inflammatory diseases.

PMID- 23131136
TI  - Feeding tolerance of preterm infants appropriate for gestational age (AGA) as
      compared to those small for gestational age (SGA).
AB  - Preterm infants are often considered too unstable to be fed enterally so they are
      exposed to complications related to a prolonged enteral fasting. Our study aims
      to compare feeding tolerance of adequate for gestational age (AGA) versus small
      for gestational age (SGA) infants and to evaluate which perinatal factors affect
      feeding tolerance (measured as time to achieve full enteral feeding, FEF). Inborn
      infants with a gestational age (GA) less than 32 weeks, born from January 2006 to
      December 2010, were eligible for this study. We enrolled 310 infants. The time to
      FEF was longer for SGA infants than for AGA, while a longer GA was associated to
      a reduced time to FEF. A beneficial effect was observed for antenatal steroids,
      while Apgar score below 7, the administration of inotrops or caffeine, the
      occurrence of sepsis or NEC and the presence of PDA were associated to a longer
      time to FEF. When evaluated jointly with a multivariate analysis, GA (p <
      0.0001), antenatal steroids prophylaxis (p = 0.002), SGA (p < 0.0001) and
      occurrence of NEC (p = 0.0002) proved to have independent prognostic impact on
      the time to FEF. Feeding tolerance is better as GA increases, and worsen in SGA
      infants. Antenatal betamethasone is effective in reducing the time to FEF in both
      AGA and SGA.

PMID- 23131137
TI  - A method for developing standardised interactive education for complex clinical
      guidelines.
AB  - BACKGROUND: Although systematic use of the Perinatal Society of Australia and New
      Zealand internationally endorsed Clinical Practice Guideline for Perinatal
      Mortality (PSANZ-CPG) improves health outcomes, implementation is inadequate. Its
      complexity is a feature known to be associated with non-compliance. Interactive
      education is effective as a guideline implementation strategy, but lacks an
      agreed definition. SCORPIO is an educational framework containing interactive and
      didactic teaching, but has not previously been used to implement guidelines. Our
      aim was to transform the PSANZ-CPG into an education workshop to develop quality
      standardised interactive education acceptable to participants for learning skills
      in collaborative interprofessional care. METHODS: The workshop was developed
      using the construct of an educational framework (SCORPIO), the PSANZ-CPG, a
      transformation process and tutor training. After a pilot workshop with key target
      and stakeholder groups, modifications were made to this and subsequent workshops
      based on multisource written observations from interprofessional participants,
      tutors and an independent educator. This participatory action research process
      was used to monitor acceptability and educational standards. Standardised
      interactive education was defined as the attainment of content and teaching
      standards. Quantitative analysis of positive expressed as a percentage of total
      feedback was used to derive a total quality score. RESULTS: Eight workshops were
      held with 181 participants and 15 different tutors. Five versions resulted from
      the action research methodology. Thematic analysis of multisource observations
      identified eight recurring education themes or quality domains used for
      standardisation. The two content domains were curriculum and alignment with the
      guideline and the six teaching domains; overload, timing, didacticism, relevance,
      reproducibility and participant engagement. Engagement was the most challenging
      theme to resolve. Tutors identified all themes for revision whilst participants
      identified a number of teaching but no content themes. From version 1 to 5, a
      significant increasing trend in total quality score was obtained; participants:
      55%, p=0.0001; educator: 42%, p=0.0004; tutor peers: 57%, p=0.0001. CONCLUSIONS:
      Complex clinical guidelines can be developed into a workshop acceptable to
      interprofessional participants. Eight quality domains provide a framework to
      standardise interactive teaching for complex clinical guidelines. Tutor peer
      review is important for content validity. This methodology may be useful for
      other guideline implementation.

PMID- 23131138
TI  - Facile template-free fabrication of hollow nestlike alpha-Fe2O3 nanostructures
      for water treatment.
AB  - Hollow nestlike alpha-Fe(2)O(3) spheres were successfully synthesized via a
      facile template-free, glycerol-mediated hydrothermal process employing microwave
      heating. The product was characterized using X-ray diffraction, field-emission
      scanning electron microscopy, transmission electron microscopy, and nitrogen
      adsorption measurements. The as-prepared product was found to consist of
      hierarchically nanostructured spheres assembled of nanorod subunits. The effect
      of the relative amount of glycerol in the reaction system on the composition and
      morphology of the products was systematically studied, and a possible formation
      mechanism of the hollow nestlike spheres was proposed. Because of their large
      surface area and unique mesoporous structure, we investigated the potential
      application of the hollow alpha-Fe(2)O(3) spheres in water treatment. With
      maximum removal capacities of 75.3, 58.5, and 160 mg g(-1) for As(V), Cr(VI), and
      Congo red, respectively, these novel nanostructures have the potential to be used
      as low-cost and efficient adsorbent materials for the removal of toxic metal ions
      and organic pollutants from water.

PMID- 23131139
TI  - Asymmetric beta-boration of alpha,beta-unsaturated N-acyloxazolidinones by
      [2.2]paracyclophane-based bifunctional catalyst.
AB  - An efficient copper-catalyzed asymmetric conjugate boration has been achieved by
      exploiting a new planar and central chiral bicyclic triazolium ligand. This
      protocol was highly efficient and gave a variety of chiral secondary
      alkylboronates in 97-99% ee. A preliminary mechanistic study supports the
      bifunctional nature of the catalyst.

PMID- 23131140
TI  - Computational differentiation of Bronsted acidity induced by alkaline earth or
      rare earth cations in zeolites.
AB  - For bi- and trivalent Me(q+) (Me = metal) cations of alkaline earth (AE) and rare
      earth (RE) metals, respectively, the formation of the nonacid MeOH((q-1)+)
      species and acid H-Ozeo group, where Ozeo is the framework atom, from water
      adsorbed at the multivalent Me(q+)(H2O) cation in cationic form zeolites was
      checked at both isolated cluster (8R or 6R + 4R) and periodic (the mordenite
      framework) levels. Both approaches demonstrate qualitative differences for the
      stability of the dissociated water between the two classes of industrial cationic
      forms if two Al atoms are closely located. The RE forms split water while the AE
      ones do not, that can be a basis of different proton transfer in the RE zeolites
      (thermodynamic control) than in the AE forms (kinetic control). The cluster
      models allow quantitatively explaining nearly equal intensities IHF ~ ILF of the
      high frequency (HF) and low frequency (LF) OH vibrations in the RE forms and
      lowered IHF ? ILF in the AE forms, where HF bands are assigned to the Me-OH
      groups in the RE and AE forms, respectively, while LF bands are assigned to the
      Si-O(H)-Al groups. The role of electrostatic terms for water dissociation in the
      RE and AE forms is discussed. 

PMID- 23131141
TI  - PhenoPhyte: a flexible affordable method to quantify 2D phenotypes from imagery.
AB  - BACKGROUND: Accurate characterization of complex plant phenotypes is critical to
      assigning biological functions to genes through forward or reverse genetics. It
      can also be vital in determining the effect of a treatment, genotype, or
      environmental condition on plant growth or susceptibility to insects or
      pathogens. Although techniques for characterizing complex phenotypes have been
      developed, most are not cost effective or are too imprecise or subjective to
      reliably differentiate subtler differences in complex traits like growth, color
      change, or disease resistance. RESULTS: We designed an inexpensive imaging
      protocol that facilitates automatic quantification of two-dimensional visual
      phenotypes using computer vision and image processing algorithms applied to
      standard digital images. The protocol allows for non-destructive imaging of
      plants in the laboratory and field and can be used in suboptimal imaging
      conditions due to automated color and scale normalization. We designed the web
      based tool PhenoPhyte for processing images adhering to this protocol and
      demonstrate its ability to measure a variety of two-dimensional traits (such as
      growth, leaf area, and herbivory) using images from several species (Arabidopsis
      thaliana and Brassica rapa). We then provide a more complicated example for
      measuring disease resistance of Zea mays to Southern Leaf Blight. CONCLUSIONS:
      PhenoPhyte is a new cost-effective web-application for semi-automated
      quantification of two-dimensional traits from digital imagery using an easy
      imaging protocol. This tool's usefulness is demonstrated for a variety of traits
      in multiple species. We show that digital phenotyping can reduce human
      subjectivity in trait quantification, thereby increasing accuracy and improving
      precision, which are crucial for differentiating and quantifying subtle
      phenotypic variation and understanding gene function and/or treatment effects.

PMID- 23131142
TI  - Application of absolute qPCR as a screening method to detect illicit 17beta
      oestradiol administration in male cattle.
AB  - It has been previously demonstrated that the progesterone receptor gene is up
      regulated in the sex accessory glands of pre-pubertal and adult male bovines
      after 17beta-oestradiol treatment. In the present study, a qualitative screening
      method was optimised to detect 17beta-oestradiol treatment using absolute
      quantification by qPCR of the progesterone receptor gene to determine the amount
      of gene expression in bulbo-urethral glands. An external standard curve was
      generated and developed with TaqMan(r) technology. Based on two in vivo
      experiments, the decision limit CCalpha, sensitivity and specificity of this
      screening method were established. Trial 1 consisted of 32 Friesian veal calves
      divided into two groups: group A (n = 12), consisting of animals treated with
      four doses of 17beta-oestradiol (5 mg week(-1) per animal); and group B (n = 20),
      consisting of control animals. Trial 2 was performed on 26 Charolaise beef cattle
      that either received five doses of 17beta-oestradiol (group C; 20 mg week(-1) per
      animal; n = 6) or remained untreated (group D; n = 20). Further, progesterone
      receptor gene expression was evaluated in beef and veal calves for human
      consumption. A specific CCalpha on 20 Piedmontese control beef cattle was
      calculated to include these animals in a field investigation. Five out of 190
      beef cattle and 26 out of 177 calves tested expressed the progesterone receptor
      gene above their respective CCalpha and they were classified as being suspected
      of 17beta-oestradiol treatment. Additionally, 58% of veal calves that tested
      suspect via qPCR exhibited histological lesions of the bulbo-urethral gland
      tissue, which are typical of oestrogen administration and are consistent with
      hyperplasia and metaplasia of the glandular epithelium.

PMID- 23131143
TI  - Toc33 and Toc64-III cooperate in precursor protein import into the chloroplasts
      of Arabidopsis thaliana.
AB  - The import of cytosolically synthesized precursor proteins into chloroplasts by
      the translocon at the outer envelope membrane of chloroplasts (TOC) is crucial
      for organelle function. The recognition of precursor proteins at the chloroplast
      surface precedes translocation and involves the membrane-inserted receptor
      subunits Toc34 and Toc159. A third receptor, Toc64, was discussed to recognize
      cytosolic complexes guiding precursor proteins to the membrane surface, but this
      function remains debated. We analysed Arabidopsis thaliana plants carrying a T
      DNA insertion in the gene encoding the Toc64 homolog Toc64-III. We observed a
      light intensity-dependent growth phenotype, which is distinct from the phenotype
      of ppi1, the previously described mutant of the TOC34 homolog TOC33. Furthermore,
      chloroplast import of the model precursor proteins pOE33 and pSSU into
      chloroplasts is reduced in protoplasts isolated from plants with impaired Toc64
      III function. This suggests that Toc64-III modulates the translocation efficiency
      in vivo. A ppi1 and toc64-III double mutant shows a significant increase in the
      transcript levels of HSP90 and TOC75-III, the latter coding for the pore-forming
      TOC component. Remarkably, the protein level of Toc75-III is significantly
      reduced, suggesting that Toc64-III and Toc33 cooperate in the insertion or
      stabilization of Toc75-III. Accordingly, the results presented support Toc64 as
      an import-relevant component of the TOC complex.

PMID- 23131144
TI  - Contrast between surface plasmon polariton-mediated extraordinary optical
      transmission behavior in epitaxial and polycrystalline Ag films in the mid- and
      far-infrared regimes.
AB  - In this Letter we report a comparative study, in the infrared regime, of surface
      plasmon polariton (SPP) propagation in epitaxially grown Ag films and in
      polycrystalline Ag films, all grown on Si substrates. Plasmonic resonance
      features are analyzed using extraordinary optical transmission (EOT)
      measurements, and SPP band structures for the two dielectric/metal interfaces are
      investigated for both types of film. At the Si/Ag interface, EOT spectra show
      almost identical features for epitaxial and polycrystalline Ag films and are
      characterized by sharp Fano resonances. On the contrary, at the air/Ag interface,
      dramatic differences are observed: while the epitaxial film continues to exhibit
      sharp Fano resonances, the polycrystalline film shows only broad spectral
      features and much lower transmission intensities. In corroboration with
      theoretical simulations, we find that surface roughness plays a critical role in
      SPP propagation for this wavelength range.

PMID- 23131145
TI  - Effect of estradiol and progesterone on metabolic biomarkers in healthy bitches.
AB  - The aim of this study was to evaluate the possible association between hormonal
      changes that occur during oestrus and biomarkers related with glucose metabolism
      (glucose and insulin), lipid metabolism (lipidic profile and BChE) and adipokines
      (adiponectin and ghrelin) in healthy bitches. For this purpose, we measured these
      analytes in serum of bitches, at two times: before (T1) and after (T2) the LH
      peak that were established according to progesterone concentrations. Increased
      levels of total cholesterol (p < 0.01), high density lipoprotein cholesterol (HDL
      C) (p < 0.01), low density lipoprotein cholesterol (LDL-C) (p < 0.01),
      adiponectin (p < 0.01) and ghrelin (p < 0.05) were observed at T2 in comparison
      with T1. No statistically significant changes were observed in serum glucose,
      insulin, homoeostasis model assessment for insulin sensitivity (HOMA),
      triglycerides and BChE. When all data of T1 and T2 were pooled, serum adiponectin
      showed positive correlation with progesterone (r = 0.353; p = 0.022) and HDL-C (r
      = 0.307; p = 0.048), and negative with insulin (r = -0.429; p = 0.005), HOMA (r =
      -0.446; p = 0.003) and BChE (r = -0.522; p < 0.001). Ghrelin showed negative
      correlation with estradiol (r = -0.701; p = 0.004). BChE was negatively
      correlated with estradiol (r = -0.441; p = 0.018) and glucose (r = -0.343; p =
      0.028), and positively with insulin (r = 0.460; p = 0.003) and HOMA (r = 0.505; p
      < 0.001). In conclusion, changes in metabolic biomarkers occur in bitches after
      LH peak, characterized by increased lipids (total cholesterol, HDL cholesterol
      and LDL cholesterol) without changes in BChE activity, and increased adiponectin
      and ghrelin concentrations, without significant changes in glucose and insulin.

PMID- 23131146
TI  - Chemosensitivity and p53; new tricks by an old dog.
AB  - The effect of TP53 mutations on chemosensitivity in breast cancer is a
      controversial issue. In an elegant paper in Cancer Cell, Jackson and colleagues
      report wtp53 protein to block anti-tumour effects of doxorubicin treatment in
      mice. p53 did so by inducing senescence, thereby preventing mitotic catastrophy
      and subsequent cell death. In contrast, while TP53 mutations have shown to
      predict response to cyclophosphamide high dose therapy, mutations in general have
      been associated with anthracycline resistance in human breast cancers. The
      challenging results from Jackson and colleagues' study elucidate a new hypothesis
      and suggest directions for future translational research in human breast cancer. 

PMID- 23131147
TI  - Screening strategy using sequential serum D-dimer assay for the detection and
      prevention of venous thromboembolism after elective brain tumor surgery.
AB  - OBJECTIVE: Venous thromboembolism (VTE) is a life-threatening complication in
      neurosurgical patients. This study retrospectively analyzed the effectiveness and
      safety of a screening strategy for the detection and prevention of VTE in
      patients undergoing elective brain tumor surgery. PATIENTS: A total of 419
      consecutive patients who underwent brain tumor surgery during 5 years were
      enrolled. At the midpoint of the study period, screening for VTE was introduced
      based on measurement of serum D-dimer level on the day after surgery and then
      once or twice every week. Anticoagulant therapy was started after the diagnosis
      of VTE. The two groups with (228 patients) and without (191 patients) screening
      were compared. RESULTS: Most of the demographic and clinical characteristics were
      relatively well balanced in the groups. VTE was diagnosed in 23 (5.5%) patients
      overall; the rate was higher in the screening group (7.0%) than in the non
      screening group (3.7%). Although the rate of VTE-related adverse events was lower
      in the screening group (1.3% vs. 2.6%), the rate of hemorrhagic complications was
      higher (2.2% vs. 0.5%). Multivariate analysis indicated that malignant histology
      and preoperative paresis were independent risk factors for the diagnosis of VTE.
      CONCLUSIONS: Many VTE patients may not exhibit signs or symptoms, so screening
      using surrogate markers for VTE (D-dimer) may be useful in the early detection of
      asymptomatic VTE. However, most distal, deep venous thrombosis in isolation is
      not life-threatening, so the added efficacy of anticoagulant agents at this stage
      has to be weighed against the risks of hemorrhagic complications, especially in
      the early postoperative period.

PMID- 23131148
TI  - Lateral sellar angiolipomas: a therapeutic challenge. Our experience on two cases
      and review of the literature.
AB  - Angiolipomas are rare benign mesenchymal tumours, most commonly found in the
      subcutaneous tissue of the extremities. These neoplasms are rarely located in the
      central nervous system (CNS), with spinal localization being the most common in
      this group. Intracranial location is extremely infrequent, and only ten cases
      have been described in the sellar region. We report on two more patients with
      skull-base (intracranial) angiolipomas, the former presented with a long history
      of headache and the latter complained diplopia. Both patients were
      postoperatively verified as angiolipoma. Neuroimaging studies and peroperative
      features are presented and the role of microsurgery is discussed. On the basis of
      these tumours' characteristics, the management strategy of choice usually does
      not consist on surgical total removal, often a partial excision could be
      satisfying to improve the patient symptomatology. Nowadays, Gamma Knife surgery
      is standing out as an effective, additional and/or alternative, treatment
      modality.

PMID- 23131149
TI  - Glioblastoma multiforme intraxial metastasis to the conus medullaris with primary
      disease under control: a rare unexpected finding.
AB  - We report on glioblastoma multiple spinal intraaxial metastases with primary
      disease radiologically under control. The case highlights glioblastoma biological
      behavior and spread mechanisms; dissemination may have occurred initially and
      been controlled by chemotherapy, or more likely, is an indicator that even if
      radiologically dormant, disease is unlikely biologically inactive.

PMID- 23131150
TI  - Regulation of leaf senescence and crop genetic improvement.
AB  - Leaf senescence can impact crop production by either changing photosynthesis
      duration, or by modifying the nutrient remobilization efficiency and harvest
      index. The doubling of the grain yield in major cereals in the last 50 years was
      primarily achieved through the extension of photosynthesis duration and the
      increase in crop biomass partitioning, two things that are intrinsically coupled
      with leaf senescence. In this review, we consider the functionality of a leaf as
      a function of leaf age, and divide a leaf's life into three phases: the
      functionality increasing phase at the early growth stage, the full functionality
      phase, and the senescence and functionality decreasing phase. A genetic framework
      is proposed to describe gene actions at various checkpoints to regulate leaf
      development and senescence. Four categories of genes contribute to crop
      production: those which regulate (I) the speed and transition of early leaf
      growth, (II) photosynthesis rate, (III) the onset and (IV) the progression of
      leaf senescence. Current advances in isolating and characterizing senescence
      regulatory genes are discussed in the leaf aging and crop production context. We
      argue that the breeding of crops with leaf senescence ideotypes should be an
      essential part of further crop genetic improvement.

PMID- 23131151
TI  - Is nicotine protective against Parkinson's disease? An experimental analysis.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder characterized by the
      loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) and its
      projections. Reports show a lower incidence of PD in smokers compared to
      nonsmokers. Nicotine reduce motor symptoms of patients already diagnosed with PD.
      However, the mechanisms underlying the effects of nicotine in the dopamine (DA)
      depleted striatum remain elusive. This study evaluates the effects of chronic
      nicotine administration on PD motor symptoms in an attempt to mimic the chronic
      self-administration of nicotine in smokers. To achieve this, we used the 6-OHDA
      hemiparkinson rat model evaluating the amphetamine/apomorphine induced circling
      behavior, in rats whose daily water intake included nicotine. We found that
      chronic nicotine reduced amphetamine (AMPH) induced circling behavior by 40%,
      whereas apomorphine (APO) increased this behavior by 230%. High-performance
      liquid chromatography (HPLC) revealed that AMPH produced a 50% decrease of DA
      release in the intact hemisphere, while on the striatum of the lesioned side,
      receptor binding assays showed an increased affinity to D1 receptors and a
      concurrent decrease in D2 receptors. c-Fos activity showed through double
      labeling, that cell types involved in nicotine action were low threshold (LTS)
      and fast spiking (FS) inter-neurons, which increased in the DA-depleted striatum.
      We also observed an increase in the activity of D1 medium spiny neurons (D1 MSN),
      a striatal population with a major role in motor control. Our results show that
      chronic nicotine does not specifically protect against degeneration, but rather
      modifies DA receptor dynamics, suggesting that it could be used as a therapeutic
      element in PD pathology.

PMID- 23131152
TI  - Neural stem cells and neurodegeneration.

PMID- 23131153
TI  - Implications of Parkinson's disease pathophysiology for the development of cell
      replacement strategies and drug discovery in neurodegenerative diseases.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative disorder
      traditionally characterized by the loss of dopaminergic neurons in the substantia
      nigra (SN) at the midbrain. The potential use of adult or embryonic stem cells,
      induced pluriputent stem (iPS) cells and endogenous neurogenesis in cell
      replacement strategies has lead to numerous studies and clinical trials in this
      direction. It is now possible to differentiate stem cells into dopaminergic
      neurons in vitro and clinical trials have shown an improvement in PD-related
      symptoms after intra-striatal embryonic transplants and acceptable cell survival
      rates on the mid term. However, clinical improvement is transitory and associated
      with a strong placebo effect. Interestingly, recent pathological studies in PD
      patients who received embryonic stem cells show that in PD patients, grafted
      neurons show PD-related pathology. In this manuscript we review the latest
      findings regarding PD pathophysiology and give an outlook on the implications of
      these findings in how cell replacement strategies for PD treatment should be
      tested. These include changes in the type of animal models used, the
      preparation/conditioning of the cells before intracerebral injection, specially
      regarding backbone chronic diseases in iPS cells and determining the optimal
      proliferation, survival, differentiation and migration capacity of the grafted
      cells.

PMID- 23131154
TI  - Pitx2 expression promotes p21 expression and cell cycle exit in neural stem
      cells.
AB  - Cortical development is a complex process that involves many events including
      proliferation, cell cycle exit and differentiation that need to be appropriately
      synchronized. Neural stem cells (NSCs) isolated from embryonic cortex are
      characterized by their ability of self-renewal under continued maintenance of
      multipotency. Cell cycle progression and arrest during development is regulated
      by numerous factors, including cyclins, cyclin dependent kinases and their
      inhibitors. In this study, we exogenously expressed the homeodomain transcription
      factor Pitx2, usually expressed in postmitotic progenitors and neurons of the
      embryonic cortex, in NSCs with low expression of endogenous Pitx2. We found that
      Pitx2 expression induced a rapid decrease in proliferation associated with an
      accumulation of NSCs in G1 phase. A search for potential cell cycle inhibitors
      responsible for such cell cycle exit of NSCs revealed that Pitx2 expression
      caused a rapid and dramatic (?20-fold) increase in expression of the cell cycle
      inhibitor p21 (WAF1/Cip1). In addition, Pitx2 bound directly to the p21 promoter
      as assessed by chromatin immunoprecipitation (ChIP) in NSCs. Surprisingly, Pitx2
      expression was not associated with an increase in differentiation markers, but
      instead the expression of nestin, associated with undifferentiated NSCs, was
      maintained. Our results suggest that Pitx2 promotes p21 expression and induces
      cell cycle exit in neural progenitors.

PMID- 23131155
TI  - From stem cells to dopamine neurons: developmental biology meets
      neurodegeneration.
AB  - Neurodegenerative disease affects tens of millions of people, worldwide, and
      comes at a cost to the public of billions of dollars. Stem cell therapy, in
      recent years, has generated a lot of enthusiasm as a novel treatment for
      neurodegenerative disease. In particular, Parkinson's disease has been identified
      as the ideal neurodegenerative disease to be treated using stem cells. Despite
      years of setbacks, recent experimental results have renewed optimism in the
      validity of stem cell therapy for the treatment of Parkinson's disease. In this
      review, we discuss advances in our understanding of the embryonic development of
      the dopamine system and the importance of these discoveries in the continued
      efforts towards stem cell therapy for Parkinson's disease.

PMID- 23131156
TI  - Neural stem cells transplanted in a mouse model of Parkinson's disease
      differentiate to neuronal phenotypes and reduce rotational deficit.
AB  - The most prominent pathological feature in Parkinson's disease (PD) is the
      progressive and selective loss of mesencephalic dopaminergic neurons of the
      nigrostriatal tract. The present study was conducted in order to investigate
      whether naive and or genetically modified neural stem/precursor cells (NPCs) can
      survive, differentiate and functionally integrate in the lesioned striatum. To
      this end, stereotaxic injections of 6-OHDA in the right ascending nigrostriatal
      dopaminergic pathway of mice and subsequent NPC transplantations were performed,
      followed by apomorphine-induced rotations and double-immunofluorescence
      experiments. Our results demonstrate that transplanted embryonic NPCs derived
      from the cortical ventricular zone of E14.5 transgenic mouse embryos expressing
      the green fluorescent protein (GFP) under control of the beta-actin promoter and
      cultured as neurospheres can survive in the host striatum for at least three
      weeks after transplantation. The percentage of surviving GFP-positive cells in
      the host striatum ranges from 0.2% to 0.6% of the total transplanted NPCs.
      Grafted cells functionally integrate in the striatum, as indicated by the
      statistically significant decrease of contralateral rotations after apomorphine
      treatment. Furthermore, we show that within the striatal environment GFP-positive
      cells differentiate into beta-III tubulin-expressing neurons, but not glial
      cells. Most importantly, GFP-positive cells further differentiate to dopaminergic
      (TH-positive) and medium size spiny (DARPP-32- positive) neuronal phenotypes.
      Over-expression of the cell cycle exit and neuronal differentiation protein Cend1
      in NPCs enhances the generation of GABAergic, but not dopaminergic, neuronal
      phenotypes after grafting in the lesioned striatum. Our results encourage the
      development of strategies involving NPC transplantation for the treatment of
      neurodegenerative diseases.

PMID- 23131157
TI  - The role of platelets and their microparticles in rehabilitation of ischemic
      brain tissue.
AB  - Stroke is a leading cause of mortality and chronic disability. Therapies aimed at
      reducing stroke related morbidity are currently limited. Therefore it is very
      important to develop effective treatments that will maximize rehabilitation after
      stroke. Current efforts in the field of cellular therapy focus on stem cell
      transplantations. This approach involves biological and ethical complications and
      therefore, the use of endogenous neural stem cells (eNSC) for repairing damage in
      various neurological disorders has been suggested. eNSCs reside in specialized
      vascular niches in defined regions, such as the subventricular zone (SVZ) of the
      lateral ventricle. These cells have an unlimited potential to create newborn
      cells. Interrelations between newborn neural and endothelial cells have an
      important role in eNSC survival, maturation, migration and differentiation and
      neurogenesis occurs in close spatio-temporal association with vessel growth in
      these niches. Previous studies have shown that application of external factors
      can boost long-term endogenous repair mechanisms in the cerebral cortex.
      Activated platelets and their microparticles contain a variety of growth and
      trophic factors essential to angiogenesis and neurogenesis and may therefore
      serve as novel therapeutic agents for brain injury. Specifically, factors from
      platelets and their microparticles may promote neurogenesis by stimulating eNSC
      proliferation, migration and differentiation, and by stimulating niche
      angiogenesis and the release of neurogenic signals from endothelial cells and
      astrocytes. In this review we will show that combined augmentation of
      angiogenesis, neurogenesis and neuroprotection using platelets and their
      microparticles is feasible and results in improved functional gain after stroke.

PMID- 23131158
TI  - Clinical implication of Meissner's corpuscles.
AB  - During the last decade skin biopsy has been confirmed as a tool to provide
      diagnostic information on some peripheral neuropathies. Most studies were focused
      on intraepithelial nerve fibers and few studies have investigated large
      myelinated fibers or whether corpuscles in human skin change quantitatively or
      qualitatively in pathologies of the peripheral or central nervous system. The
      main objective of this article is to provide a comprehensive review of Meissner's
      corpuscles including their distribution, density and age changes, development,
      molecular composition, cellular anatomy and physiology. We also describe their
      involvement in several pathologies and suggest including this dermal structure in
      the routine study of skin biopsies, looking for changes to be used as potential
      markers for several disorders. Finally the article draws the main aspects of how
      to study Meissner's corpuscles in skin biopsies and gives a view on future
      perspectives for implementing their use in clinical practice.

PMID- 23131159
TI  - Angiogenesis and hypoxia in glioblastoma: a focus on cancer stem cells.
AB  - Many studies have elucidated the important role played by the tumor
      microenvironment in cancer evolution. In particular the formation of hypoxic
      areas within the expanding mass of a solid tumor and the consequent induction of
      an angiogenic switch are crucial steps that shape tumor progression. Focusing on
      glioblastoma multiforme (GBM), the most common and lethal brain cancer in the
      adult, I will review recent data that show how the microenvironment regulates
      crucial functions of glioblastoma stem cells (GSCs) which in turn affect the
      angiogenic process.

PMID- 23131160
TI  - Evidence of nestin-positive cells in the human cutaneus Meissner and Pacinian
      corpuscles.
AB  - Nestin is an intermediate filament protein expressed in neuroepithelial stem
      cells during development and it is later replaced by cell specific neuronal or
      glial filaments. Nevertheless, nestin+ cells remain within adult tissues and they
      can be regarded as potential neural stem cell (NSC). Nestin+ cells have been
      detected in Schwann cells related with sensory corpuscles of rodent and they have
      been demonstrated to be NSC. We have investigated the existence of nestin+ in
      human cutaneous cells Meissner and Pacinian corpuscles through the use of
      immunohistochemistry techniques and in situ hybridization. S100 protein (also
      regarded as a marker for NSC) and vimentin (the intermediate filament of mature
      Schwann cells in sensory corpuscles) were also investigated. The results show
      that the adult human cutaneous sensory Meissner and Pacinian corpuscles contains
      a small population of Schwann-related cells (vimentin+) which on the basis of
      their basic immunohistochemical characteristics (S100 protein+, nestin+) can be
      potential NSCs. Cells sharing identical immunohistochemical profile were also
      found in the close vicinity of Meissner corpuscles. Because their localization
      they are easily accessible and may represent a peripheral niche of NSC to be used
      for therapeutic goals.

PMID- 23131161
TI  - Retracted: Hypocretin (orexin) cell transplantation diminishes narcoleptic-like
      sleep behavior in rats.
AB  - Arias-Carrion, O.; Drucker-Colin, R.; Murillo-Rodriguez, E. "Hypocretin (orexin)
      cell transplantation diminishes narcoleptic-like sleep behavior in rats." CNS
      Neurol. Disord. Drug Targets, 2011,11(7). The above-cited paper has been
      retracted from CNS & Neurological Disorders-Drug Targets at the request of the
      authors. The authors advised the Journal of their intention to perform additional
      experiments in order to strengthen their initial results, at which time an
      amended manuscript may be submitted.

PMID- 23131163
TI  - Activin and TGF-beta effects on brain development and neural stem cells.
AB  - Transforming Growth Factor-beta (TGF-beta) family members are ubiquitously
      expressed, participating in the regulation of many processes in different cell
      types both in embryonic and adult stages. Several members of this family,
      including Activins, TGF-beta1-3 and Nodal, have been implicated in the
      development and maintenance of various organs, in which stem cells play important
      roles. Although TGF-beta was initially considered an injury-related cytokine, it
      became clear that not only TGF-beta, but other members of this family, play
      critical roles in morphogenesis and cell lineage specification. During brain
      development, Activin and TGF-betas as well as their cognate receptors, are
      expressed in different patterns. The roles of Activin and TGF-beta during CNS
      development are sometimes contradictory, because these proteins present different
      actions depending on the cell type and the context. The aim of this review is to
      summarize current information on the actions of TGF-beta members during
      developing brain, and also on Neural Stem/Progenitor Cells (NSPC). We focus on
      the TGF-beta subgroup, specifically on the effects of TGF-beta1 and Activin A. In
      the first section we describe the main characteristics of the ligands, its
      receptors as well as the proteins and mechanisms involved in signaling. Next, we
      discuss the main advances concerning TGF-beta1 and Activin actions during brain
      development and their roles in NSPC fate decision and neuroprotection both in
      vitro and in vivo. The emerging picture from these studies suggests that these
      growth factors can be used to manipulate neurogenesis and might help to achieve
      restoration after brain deterioration.

PMID- 23131164
TI  - Insulin growth factor-I promotes functional recovery after a focal lesion in the
      dentate gyrus.
AB  - The adult brain is plastic and able to reorganize structurally and functionally
      after damage. Growth factors are key molecules underlying the recovery process
      and among trophic molecules, Insulin-Like Growth Factor-I (IGF-I) is of
      particular interest given that it modulates neuronal and glial responses in the
      hippocampus including neurogenesis, which has been proposed as a mechanism of
      neurorepair. In this study we analyzed the effect of intracerebroventricular
      chronic infusion of IGF-I on functional recovery and morphological restoration
      after the induction of an excitotoxic lesion in the dentate gyrus (DG) of young
      adult rats. Our results show that the lesion impairs contextual fear memory which
      is a DG dependent task, but not cued fear memory or performance in the open field
      motor task, which are independent of the DG integrity. Chronic administration of
      IGF-I, but not vehicle, promotes functional recovery to control levels in injured
      subjects. Analysis in NeuN immunoprocessed tissue revealed that the lesion volume
      was not different between groups and that the DG was not evidently restructured
      in the IGF-I treated group. Glial fibrillary acidic protein (GFAP) analysis
      revealed an increased astrocytic response in the injured region in both groups
      and Doublecortin (DCX) analysis showed a similar increase in number of newly born
      neurons in both groups. However, a remarkable increase in young neurons dendritic
      arborization was observed in the IGF-I treated group. These results provide
      evidence for IGF-I as a molecule mediating functional and cellular plasticity
      during a reorganization process after damage to a neurogenic niche.

PMID- 23131165
TI  - Research highlights. The genetic basis of "running for longevity".

PMID- 23131162
TI  - Neurovascular signals suggest a propagation mechanism for endogenous stem cell
      activation along blood vessels.
AB  - Stem cell-based therapies for central nervous system disorders are intensely
      pursued. Such approaches can be divided into two categories: Transplantation
      based, and those that aim to pharmacologically target the endogenous stem cell
      population in the tissue. Endogenous stem cell - based strategies avoid the
      problem of immune incompatibility between the host and the grafted cells. They
      also avoid the placement of a large amount of cells in confined areas, a
      manipulation which alters the characteristics of the neurovascular
      microenvironment. We show here that massive pharmacological activation (increase
      in cell numbers) of the endogenous neural stem cell population in the adult
      rodent brain maintains the cytoarchitecture of the neurovascular niche. Distances
      between adjacent stem cells (identified by expression of Hes3) are maintained
      above a minimum. Hes3+ cells maintain their physical association with blood
      vessels. These results also suggest a mechanism by which the activation signal
      from the lateral ventricle can be propagated to areas a long distance away from
      the lateral ventricles, through autocrine/paracrine actions between adjacent
      Hes3+ cells, along blood vessels. Finally, powerful effects of angiopoietin 2 on
      Hes3+ cells help explain the prevalence of proliferating endogenous neural stem
      cells close to the subventricular zone (an area of high angiopoietin 2
      concentration) and the quiescent state of stem cells away from the ventricles and
      their tight physical association with blood vessels (which express high levels of
      angiopoietin 1, a cytokine that opposes angiopoietin 2 functions).

PMID- 23131169
TI  - Focal dermal hypoplasia due to a novel mutation in a boy with Klinefelter
      syndrome.
AB  - A boy was born with multiple anomalies, including right hemifacial microsomia,
      eye abnormalities, syndactyly, right hand ectrodactyly, hypoplastic nails,
      omphalocele, bladder exstrophy, renal dilatation, and splayed symphysis pubis.
      The skin was also abnormal, with atrophic skin plaques and areas of
      telangiectasia along the lines of Blaschko. The karyotype was 47,XXY (Klinefelter
      syndrome). He was found to have a heterozygous mutation in the PORCN gene. He
      exhibited the classical features of focal dermal hypoplasia. Fewer than 15% of
      reported cases are male when it is thought to be due to postzygotic mutation and
      thus mosaic. This is the first reported boy to have heterozygous mutation for
      Goltz syndrome who survived due to the extra X chromosome. 

PMID- 23131170
TI  - Purification and characterization of a surfactin-like molecule produced by
      Bacillus sp. H2O-1 and its antagonistic effect against sulfate reducing bacteria.
AB  - BACKGROUND: Bacillus sp. H2O-1, isolated from the connate water of a Brazilian
      reservoir, produces an antimicrobial substance (denoted as AMS H2O-1) that is
      active against sulfate reducing bacteria, which are the major bacterial group
      responsible for biogenic souring and biocorrosion in petroleum reservoirs. Thus,
      the use of AMS H2O-1 for sulfate reducing bacteria control in the petroleum
      industry is a promising alternative to chemical biocides. However, prior to the
      large-scale production of AMS H2O-1 for industrial applications, its chemical
      structure must be elucidated. This study also analyzed the changes in the wetting
      properties of different surfaces conditioned with AMS H2O-1 and demonstrated the
      effect of AMS H2O-1 on sulfate reducing bacteria cells. RESULTS: A lipopeptide
      mixture from AMS H2O-1 was partially purified on a silica gel column and
      identified via mass spectrometry (ESI-MS). It comprises four major components
      that range in size from 1007 to 1049 Da. The lipid moiety contains linear and
      branched beta-hydroxy fatty acids that range in length from C13 to C16. The
      peptide moiety contains seven amino acids identified as Glu-Leu-Leu-Val-Asp-Leu
      Leu.Transmission electron microscopy revealed cell membrane alteration of sulfate
      reducing bacteria after AMS H2O-1 treatment at the minimum inhibitory
      concentration (5 MUg/ml). Cytoplasmic electron dense inclusions were observed in
      treated cells but not in untreated cells. AMS H2O-1 enhanced the osmosis of
      sulfate reducing bacteria cells and caused the leakage of the intracellular
      contents. In addition, contact angle measurements indicated that different
      surfaces conditioned by AMS H2O-1 were less hydrophobic and more electron-donor
      than untreated surfaces. CONCLUSION: AMS H2O-1 is a mixture of four surfactin
      like homologues, and its biocidal activity and surfactant properties suggest that
      this compound may be a good candidate for sulfate reducing bacteria control.
      Thus, it is a potential alternative to the chemical biocides or surface coating
      agents currently used to prevent SRB growth in petroleum industries.

PMID- 23131171
TI  - Influenza virus subpopulations: interferon induction-suppressing particles
      require expression of NS1 and act globally in cells; UV irradiation of interferon
      inducing particles blocks global shut-off and enhances interferon production.
AB  - Influenza virus populations contain several subpopulations of noninfectious
      biologically active particles that are measured by the unique phenotypes they
      express. Two of these subpopulations were studied: (1) interferon (IFN)-inducing
      particles (IFP) and (2) IFN induction-suppressing particles (ISP). ISP are
      dominant in cells coinfected with one or more IFP; they completely suppress IFN
      production in cells otherwise programmed to induce it. Influenza virus ISP were
      shown to act in host cells in a nonspecific and global manner, suppressing IFN
      induction independent of the family of viruses serving as IFN inducers. ISP must
      be present within the first 3 h of coinfection with IFP to be maximally
      effective; by 7 hpi IFN induction/production is refractory to the action of
      superinfecting ISP. UV target and thermal inactivation analyses revealed that ISP
      activity was dependent solely on the expression of the NS gene. Low doses of UV
      radiation enhanced by ~10-fold the already high IFN-inducing capacity of a virus
      that expressed truncated NS1. There was no change in the number of IFP, implying
      that the production of IFN/cell had increased. We postulated that preventing
      degradation of cellular RNA pol II by viral polymerase prolonged the
      transcription of cellular mRNA, including IFN mRNA, to enhance the IFN-inducing
      capacity of the cell without any increase in the number of IFP. These studies
      point to the dueling roles of IFP and ISP in modulating IFN induction/production,
      the former activity being critical to the efficacy of live attenuated influenza
      vaccines.

PMID- 23131172
TI  - Vitamin D and neonatal immune function.
AB  - Vitamin D deficiency is widespread in the neonatal and paediatric population of
      northern latitudes, particularly in children of African, Middle Eastern and Asian
      ethnicity. This is associated with diminished immune function and increases the
      risk of Th1 autoimmune diseases like type 1 diabetes. Epidermiological studies
      have also shown a link between vitamin D deficiency in children and a more severe
      course of illness with lower respiratory tract infection or Respiratory Syncitial
      Virus (RSV) bronchiolitis. The mechanism by which vitamin D enhances immunity is
      complex. It acts through the innate immune system by inducing antimicrobial
      peptides in epithelial cells, neutrophils and macrophages. The role of Vitamin D
      in neonatal and paediatric immunomodulation requires further study.

PMID- 23131173
TI  - Intermittent preexcitation and the risk of sudden death: the exception that
      proves the rule?

PMID- 23131174
TI  - Vestibular rehabilitation using the Nintendo(r) Wii Balance Board -- a user
      friendly alternative for central nervous compensation.
AB  - CONCLUSION: The Nintendo(r) Wii Balance Board is a cost-effective and user
      friendly alternative to other popular frequently used systems that aid vestibular
      compensation, particularly in elderly patients. In addition, further treatment in
      the home environment is possible. OBJECTIVE: This cohort study was designed to
      investigate the impact of the Nintendo(r) Wii Balance Board as a visual
      compensation device after acute vestibular neuritis. METHODS: Subjects were
      randomly assigned to one of two treatment groups. Group A (n = 37) performed
      customized exercises with the Nintendo(r) Wii Balance Board. Group B (n = 34)
      performed only two elected exercises as a control group for comparison of the
      results. Both groups underwent additive therapy with steroids (intravenous) in
      decreasing doses (250 mg decreasing to 25 mg over 10 days). The Sensory
      Organization Test (SOT), Dizziness Handicap Inventory (DHI), Vertigo Symptom
      Scale (VSS), and Tinneti questionnaire were evaluated immediately before
      treatment (baseline), at the end of treatment, i.e. at day 5, and after 10 weeks.
      RESULTS: The early use of a visual feedback system in the context of the balance
      training supports the central nervous vestibular compensation after peripheral
      labyrinthine disorders. Patients in group B (without training) required a longer
      in-patient stay (average 2.4 days, SD 0.4) compared with patients following early
      Wii rehabilitation. The absence of nystagmus under Frenzel's goggles in group A
      was observed 2.1 days (SD 0.5) earlier than in group B. Group A showed
      significantly better results in the SOT, DHI, VSS, and Tinneti questionnaire at
      all time points measured (p < 0.05).

PMID- 23131175
TI  - Synthesis of carbon nanotube-anatase TiO2 sub-micrometer-sized sphere composite
      photocatalyst for synergistic degradation of gaseous styrene.
AB  - The carbon nanotube (CNT)-sub-micrometer-sized anatase TiO2 sphere composite
      photocatalysts were synthesized by a facile one-step hydrothermal method using
      titanium tetrafluoride as titanium source and CNTs as structure regulator.
      Various technologies including X-ray diffraction, UV-visible absorption spectra,
      N2 adsorption-desorption, scanning electron microscopy, and transmission electron
      microscopy were employed to characterize the structure properties of the prepared
      composite photocatalysts. The results indicated that the composite photocatalysts
      consisted of CNTs wrapping around the sub-micrometer-sized anatase TiO2 spheres
      with controllable crystal facets and that the aggregated particles with average
      diameter ranged from 200 to 600 nm. The fabricated composite photocatalysts were
      used to degrade gaseous styrene in this work. As expected, a synergistic effect
      that remarkably enhancing the photocatalytic degradation efficiency of gaseous
      styrene by the prepared composite photocatalysts was observed in comparison with
      that the degradation efficiency using pure anatase TiO2 and the adsorption of
      CNTs. Similar results were also confirmed in the decolorization of liquid methyl
      orange. Further investigation demonstrated that the synergistic effect in the
      photocatalytic activity was related to the structure of the sub-micrometer-sized
      anatase TiO2 spheres and the significant roles of CNTs in the composite
      photocatalysts. By controlling the content of CNTs, the content of TiO2 or the
      temperature during the hydrothermal synthesis process, anatase TiO2 spheres with
      controllable crystallite size and dominant crystal facets such as {001}, {101},
      or polycrystalline could be obtained, which was beneficial for the increase in
      the synergistic effect and further enhancement of the photocatalytic
      efficiencies.

PMID- 23131176
TI  - Conduction slowing contributes to spontaneous ventricular arrhythmias in
      intrinsically active murine RyR2-P2328S hearts.
AB  - INTRODUCTION: The familial condition catecholaminergic polymorphic ventricular
      tachycardia (CPVT) is characterized by episodic bidirectional ventricular
      tachycardia (BVT), polymorphic ventricular tachycardia (PVT), and ventricular
      fibrillation following adrenergic challenge. It is associated with mutations
      involving the cardiac ryanodine receptor (RyR2). METHODS AND RESULTS: We explored
      for a slowing of myocardial conduction that could potentially result in a
      substrate for the spontaneous arrhythmogenesis that was observed following
      introduction of isoproterenol and caffeine in intrinsically beating murine RyR2
      P2328S hearts. Such pharmacological challenge increased the number of arrhythmic
      episodes in electrocardiographic recordings from intact anesthetized mice, with
      the greatest effects in the homozygote RyR2(S/S). Arrhythmias took the form of
      bigeminy, BVT, monomorphic ventricular tachycardia, and PVT, as found in human
      CPVT. Ventricular epicardial conduction velocities (CVs) measured using
      multielectrode array recordings and maximum action potential upstroke rates,
      (dV/dt)(max), measured using intracellular microelectrodes were indistinguishable
      in untreated wild-type (WT) and RyR2(S/S). Pharmacological challenge of
      RyR2(S/S), but not WT hearts, then reduced CV and (dV/dt)(max) and also revealed
      a strongly arrhythmic phenotype. There was no evidence of gross structural or
      fibrotic changes in either RyR2(+/S) or RyR2(S/S) hearts on light microscopy.
      CONCLUSIONS: We associate altered ventricular myocardial CV potentially resulting
      in arrhythmogenic substrate with arrhythmic properties associated with genetic
      RyR2 alterations for the first time.

PMID- 23131177
TI  - Characterization of substituted phenylpropylamides as highly selective agonists
      at the melatonin MT2 receptor.
AB  - Melatonin is a widely distributed hormone that regulates several major
      physiological processes, including the circadian rhythm and seasonal adaptation.
      The two subtypes of mammalian G protein-coupled melatonin receptors are primarily
      responsible for mediating the actions of melatonin. Because synthetic melatonin
      agonists have considerable therapeutic potentials in modulating insomnia and
      circadian- related sleep disorders, it is highly desirable to develop subtype
      selective melatoninergic compounds. The pharmacological potencies of a series of
      substituted N-[3-(3-methoxyphenyl)propyl] amides towards human melatonin MT(1)
      and MT(2) receptors were evaluated by the FLIPR high-throughput screening assay,
      whilst their subtype-selectivity was subsequently verified with ERK
      phosphorylation and cAMP assays. Structure-activity relationship analysis of
      highly potent subtype-selective ligands (MT(2) EC(50) 10-90 pM) revealed that a
      benzyloxyl substituent incorporated at C6 position of the 3-methoxyphenyl ring
      dramatically enhanced the MT(2) potency and at the same time decreased MT(1)
      potency. Incorporation of structural moieties conferring the subtype selectivity
      produced several extremely potent MT(2)-selective ligands. The most potent
      subtype-selective ligand, 2q had a substantially higher potency for MT(2)
      receptor than melatonin for elevation of [Ca(2+)]i and inhibition of forskolin
      elevated cAMP. Representative MT(2)-selective ligands also induced ERK
      phosphorylation in both recombinant and native cell lines, and no cross
      reactivity to 17 other GPCRs could be detected. These ligands represent
      invaluable tools for delineating the functional roles of distinct melatonin
      receptor subtypes and are viable candidates for drug development.

PMID- 23131178
TI  - Characterization of blood biochemical markers during aging in the Grey Mouse
      Lemur (Microcebus murinus): impact of gender and season.
AB  - BACKGROUND: Hematologic and biochemical data are needed to characterize the
      health status of animal populations over time to determine the habitat quality
      and captivity conditions. Blood components and the chemical entities that they
      transport change predominantly with sex and age. The aim of this study was to
      utilize blood chemistry monitoring to establish the reference levels in a small
      prosimian primate, the Grey Mouse Lemur (Microcebus murinus). METHOD: In the
      captive colony, mouse lemurs may live 10-12 years, and three age groups for both
      males and females were studied: young (1-3 years), middle-aged (4-5 years) and
      old (6-10 years). Blood biochemical markers were measured using the VetScan
      Comprehensive Diagnostic Profile. Because many life history traits of this
      primate are highly dependent on the photoperiod (body mass and reproduction), the
      effect of season was also assessed. RESULTS: The main effect of age was observed
      in blood markers of renal functions such as creatinine, which was higher among
      females. Additionally, blood urea nitrogen significantly increased with age and
      is potentially linked to chronic renal insufficiency, which has been described in
      captive mouse lemurs. The results demonstrated significant effects related to
      season, especially in blood protein levels and glucose rates; these effects were
      observed regardless of gender or age and were likely due to seasonal variations
      in food intake, which is very marked in this species. CONCLUSION: These results
      were highly similar with those obtained in other primate species and can serve as
      references for future research of the Grey Mouse Lemur.

PMID- 23131180
TI  - Adaptation of a web-based, open source electronic medical record system platform
      to support a large study of tuberculosis epidemiology.
AB  - BACKGROUND: In 2006, we were funded by the US National Institutes of Health to
      implement a study of tuberculosis epidemiology in Peru. The study required a
      secure information system to manage data from a target goal of 16,000 subjects
      who needed to be followed for at least one year. With previous experience in the
      development and deployment of web-based medical record systems for TB treatment
      in Peru, we chose to use the OpenMRS open source electronic medical record system
      platform to develop the study information system. Supported by a core technical
      and management team and a large and growing worldwide community, OpenMRS is now
      being used in more than 40 developing countries. We adapted the OpenMRS platform
      to better support foreign languages. We added a new module to support double data
      entry, linkage to an existing laboratory information system, automatic upload of
      GPS data from handheld devices, and better security and auditing of data changes.
      We added new reports for study managers, and developed data extraction tools for
      research staff and statisticians. Further adaptation to handle direct entry of
      laboratory data occurred after the study was launched. RESULTS: Data collection
      in the OpenMRS system began in September 2009. By August 2011 a total of 9,256
      participants had been enrolled, 102,274 forms and 13,829 laboratory results had
      been entered, and there were 208 users. The system is now entirely supported by
      the Peruvian study staff and programmers. CONCLUSIONS: The information system
      served the study objectives well despite requiring some significant adaptations
      mid-stream. OpenMRS has more tools and capabilities than it did in 2008, and
      requires less adaptations for future projects. OpenMRS can be an effective
      research data system in resource poor environments, especially for organizations
      using or considering it for clinical care as well as research.

PMID- 23131181
TI  - A story told by a single nanowire: optical properties of wurtzite GaAs.
AB  - The optical properties of the wurtzite (WZ) GaAs crystal phase found in nanowires
      (NWs) are a highly controversial topic. Here, we study high-quality pure WZ
      GaAs/AlGaAs core-shell NWs grown by Au-assisted molecular beam epitaxy (MBE) with
      microphotoluminescence spectroscopy (MU-PL) and (scanning) transmission electron
      microscopy on the very same single wire. We determine the room temperature (294
      K) WZ GaAs bandgap to be 1.444 eV, which is ~20 meV larger than in zinc blende
      (ZB) GaAs, and show that the free exciton emission at 15 K is at 1.516 eV. On the
      basis of time- and temperature-resolved MU-PL results, we propose a Gamma(8)
      conduction band symmetry in WZ GaAs. We suggest a method for quantifying the
      optical quality of NWs, taking into consideration the difference between the room
      and low temperature integrated PL intensity, and demonstrate that Au-assisted
      GaAs/AlGaAs core-shell NWs can have high PL brightness up to room temperature.

PMID- 23131182
TI  - Vitamin D in the maternal-fetal-neonatal interface: clinical implications and
      requirements for supplementation.
AB  - Identification of the current evidence regarding the pathophysiological and
      clinical facets of vitamin D in the maternal-fetal-neonatal interface is of value
      because of the significance of the vitamin D endocrine system in human health and
      high prevalence of vitamin D deficiency in mothers and their infants. Although
      many questions have still not been answered by the existing literature, we found
      evidence that: (i) during pregnancy vitamin D participates in fetal skeletal
      mineralization and growth, (ii) neonatal vitamin D levels are dependent on the
      maternal vitamin D status at delivery, (iii) a vitamin D sufficient status at
      birth may decrease the risk for the development of asthma and type 1 diabetes
      mellitus in later life, (iv) recommendations for maintaining serum 25
      hydroxyvitamin D [25(OH)D] levels >=32 ng/mL to avoid secondary
      hyperparathyroidism in adults have not been applied to mothers and their infants,
      (v) American Academy of Pediatrics recommended supplementation of 400 IU of
      vitamin D per day is sufficient only for infants who are born with normal vitamin
      D levels and (vii) supplementation of lactating mothers with high doses of
      vitamin D (4000 IU/d) allows the achievement of optimal 25(OH)D concentrations
      (>32 ng/mL) in the maternal and infant serum without any risk of hypervitaminosis
      D in the mother. We believe that inconsistency in the recognition of sufficient
      levels of vitamin D in mothers and their infants affects the identification of
      adequate doses for vitamin D supplementation during pregnancy, lactation and
      infancy.

PMID- 23131183
TI  - Hydrologic linkages between a climate oscillation, river flows, growth, and wood
      Delta13C of male and female cottonwood trees.
AB  - To investigate climatic influence on floodplain trees, we analysed interannual
      correspondences between the Pacific Decadal Oscillation (PDO), river and
      groundwater hydrology, and growth and wood (13)C discrimination (Delta(13)C) of
      narrowleaf cottonwoods (Populus angustifolia) in a semi-arid prairie region. From
      the Rocky Mountain headwaters, river discharge (Q) was coordinated with the PDO
      (1910-2008: r(2) = 0.46); this pattern extended to the prairie and was amplified
      by water withdrawal for irrigation. Floodplain groundwater depth was correlated
      with river stage (r(2) = 0.96), and the cottonwood trunk basal area growth was
      coordinated with current- and prior-year Q (1992-2008: r(2) = 0.51), increasing
      in the mid-1990s, and decreasing in 2000 and 2001. Annual Delta(13)C decreased
      during low-flow years, especially in trees that were higher or further from the
      river, suggesting drought stress and stomatal closure, and male trees were more
      responsive than females (-0.86 versus -0.430/00). With subsequently increased
      flows, Delta(13)C increased and growth recovered. This demonstrated the linkages
      between hydroclimatic variation and cottonwood ecophysiology, and we conclude
      that cottonwoods will be vulnerable to drought from declining river flows due to
      water withdrawal and climate change. Trees further from the river could be
      especially affected, leading to narrowing of floodplain forests along some
      rivers.

PMID- 23131184
TI  - Privileged scaffolds or promiscuous binders: a glance of pyrrolo[2,1
      f][1,2,4]triazines and related bridgehead nitrogen heterocycles in medicinal
      chemistry.
AB  - Pyrrolo[2,1-f][1,2,4]triazine template, a unique bridgehead nitrogen heterocycle,
      certainly deserves the title of "privileged scaffold" in the drug discovery field
      because of the versatility and potential to yield derivatives with a wide range
      of biological activities, such as anti-anaplastic lymphoma kinase (ALK), Janus
      kinase 2 (JAK2), VEGFR-2, EGFR and/or HER2, Met kinase, p38alpha mitogen
      activated protein (MAP) kinase and insulin-like growth factor receptor (IGF-1R)
      kinase activities, etc. These different biological properties of pyrrolo[2,1
      f][1,2,4]triazine derivatives have motivated new studies in searching for novel
      derivatives with improved activity and also other applications in pharmaceutical
      field. However, no systematic review is available in the literature on the
      pyrrolo[2,1- f][1,2,4]triazine derivatives concerning the design of potent drug
      like compounds. Owing to the importance of this heterocyclic system, the present
      paper is an attempt to the pharmacological activities, structural modifications
      and the structure-activity relationship (SAR) reported for bridgehead nitrogen
      heterocycles in the current literature, making an effort to highlight the
      importance and therapeutic potentials of the pyrrolo[2,1-f][1,2,4]triazine
      scaffold and its bridgehead nitrogen bioisosters as heterocyclic privileged
      medicinal scaffolds.

PMID- 23131185
TI  - Pharmacokinetics and safety of 0.5% ivermectin lotion for head louse
      infestations.
AB  - The safety of a novel 0.5% ivermectin lotion (IVL) and potential for ivermectin
      absorption after application was investigated in an open-label study in young
      children, and a human repeat insult patch test (HRIPT) and cumulative irritation
      test (CIT) assessed any potential for cumulative dermal irritation and contact
      sensitization. In the pharmacokinetic and safety study, 30 head louse-infested
      children ages 6 months to 3 years received a 10-minute application of IVL on day
      1. Blood was collected before application; 0.5, 1, and 6 hours after rinsing; and
      on days 2 and 8. Samples from 20 subjects were assayed for ivermectin (test
      sensitivity 0.05 ng/mL). Liver panel and complete blood counts were completed for
      all subjects. For the HRIPT/CIT, occlusive patches containing IVL or vehicle
      control lotion (CL) were repeatedly applied to 220 healthy adult subjects to
      assess contact sensitization; for cumulative dermal irritation testing,
      additional patches with normal saline and sodium dodecyl sulfate (SDS) were
      applied to 36 subjects. In the open-label study, all detected ivermectin plasma
      concentrations were <1 ng/mL. No safety signals emerged, and treatment was well
      tolerated. In the HRIPT/CIT, IVL was significantly less irritating than normal
      saline and SDS, with no evidence of dermal irritation or sensitization in human
      skin. IVL was safe when applied topically, absorption was de minimus, there was
      no evidence of irritation or sensitization from repeated exposures, and results
      support the safety of topical IVL use in children as young as 6 months.

PMID- 23131186
TI  - Encapsulation of amoxicillin within laponite-doped poly(lactic-co-glycolic acid)
      nanofibers: preparation, characterization, and antibacterial activity.
AB  - We report a facile approach to encapsulating amoxicillin (AMX) within laponite
      (LAP)-doped poly(lactic-co-glycolic acid) (PLGA) nanofibers for biomedical
      applications. In this study, a synthetic clay material, LAP nanodisks, was first
      used to encapsulate AMX. Then, the AMX-loaded LAP nanodisks with an optimized AMX
      loading efficiency of 9.76 +/- 0.57% were incorporated within PLGA nanofibers
      through electrospinning to form hybrid PLGA/LAP/AMX nanofibers. The loading of
      AMX within LAP nanodisks and the loading of LAP/AMX within PLGA nanofibers were
      characterized via different techniques. In vitro drug release profile,
      antimicrobial activity, and cytocompatibility of the formed hybrid PLGA/LAP/AMX
      nanofibers were also investigated. We show that the loading of AMX within LAP
      nanodisks does not lead to the change of LAP morphology and crystalline structure
      and the incorporation of LAP/AMX nanodisks does not significantly change the
      morphology of the PLGA nanofibers. Importantly, the loading of AMX within LAP
      doped PLGA nanofibers enables a sustained release of AMX, much slower than that
      within a single carrier of LAP nanodisks or PLGA nanofibers. Further
      antimicrobial activity and cytocompatibility assays demonstrate that the
      antimicrobial activity of AMX toward the growth inhibition of a model bacterium
      of Staphylococcus aureus is not compromised after being loaded into the hybrid
      nanofibers, and the PLGA/LAP/AMX nanofibers display good cytocompatibility,
      similar to pure PLGA nanofibers. With the sustained release profile and the
      reserved drug activity, the organic/inorganic hybrid nanofiber-based drug
      delivery system may find various applications in tissue engineering and
      pharmaceutical science.

PMID- 23131187
TI  - Impaired aortic elastic properties in patients with adult-onset hypogonadism.
AB  - BACKGROUND: Recent studies have shown a strong relationship between testosterone
      levels and vasomotor actions. The aim of this study is to compare the elastic
      properties of the aorta in male patients with hypogonadism and eugonadal healthy
      control subjects. METHOD: A total of 22 male with hypogonadism (mean age: 35.2 +/
      9.5 years, mean disease duration: 5.3 +/- 1.8 years) and 25 age-, sex- and
      weight-matched eugonadal healthy subjects (mean age: 34.5 +/- 8.2 years) were
      enrolled in the study. Aortic stiffness (beta) index, aortic strain (AoS) and
      aortic distensibility (AoD) were calculated from the aortic diameters measured by
      transthoracic echocardiography and blood pressure obtained by sphygmomanometer.
      RESULTS: The routinely performed echocardiographic parameters were similar
      between patient and control groups. There were significant differences between
      the control and patient groups in beta index (1.75 +/- 0.44 vs 2.68 +/- 1.72, p <
      0.001), AoS (18.52 +/- 6.44 vs 12.35 +/- 3.88%, p < 0.001) and AoD (7.56 +/- 2.86
      vs 3.96 +/- 1.24, 10(-6) cm(2)/dyn, p < 0.001). There were statistically
      significant positive correlations between the serum total testosterone level and
      AoD (r = 0.539, p < 0.001) and AoS (r = 0.372, p = 0.036); moreover, there was a
      negative correlation between the serum total testosterone level and beta index (r
      = - 0.462, p = 0.001). In multivariate analysis, serum total testosterone level
      was significantly related with AoD, AoS and beta index (respectively, RR = 2.88,
      p = 0.004; RR = 3.45, p = 0.001; RR = 2.64, p = 0.01). CONCLUSION: The study
      results showed that aortic elasticity was impaired in patients with hypogonadism.
      We also have demonstrated a statistically significant correlation between aortic
      elastic properties and the serum total testosterone level.

PMID- 23131188
TI  - Acetic-acid-mediated miscibility toward electrospinning homogeneous composite
      nanofibers of GT/PCL.
AB  - In tissue engineering research, there has recently been considerable interest in
      using electrospun biomimetic nanofibers of hybrids, in particular, from natural
      and synthetic polymers for engineering different tissues. However, phase
      separation between a pair of much dissimilar polymers might give rise to
      detrimental influences on both the electrospinning process and the resultant
      fiber performance. A representative natural-synthetic hybrid of gelatin (GT) and
      polycaprolactone (PCL) (50:50) was employed to study the phase separation
      behavior in electrospinning of the GT/PCL composite fibers. Using
      trifluoroethanol (TFE) as the cosolvent of the two polymers, observation of
      visible sedimentation and flocculation from dynamic light scattering analysis of
      the GT/PCL/TFE mixture both showed that phase separation does occur in just a few
      hours. This consequently led to gradually deteriorated fiber morphologies (e.g.,
      splash, fiber bonding, and varied fiber size) over time during electrospinning
      GT/PCL. Quantitative analysis also indicated that the ratio of GT to PCL in the
      resultant GT/PCL fibers was altered over time. To address the phase separation
      related issues, a tiny amount (<0.3%) of acetic acid was introduced to improve
      the miscibility, which enabled the originally turbid solution to become clear
      immediately and to be single-phase stable for more than 1 week. Nanofibers thus
      obtained also appeared to be thinner, smooth, and homogeneous with enhanced
      performance in wettability and mechanical properties. Given the versatility and
      widely uses of the electrospun GT/PCL and other similar natural-synthetic hybrid
      systems in constructing tissue-engineered scaffolds, this work may offer a facile
      and effective approach to achieve finer and compositionally homogeneous hybrid
      nanofibers for effective applications.

PMID- 23131189
TI  - Membrane-active peptides derived from picornavirus 2B viroporin.
AB  - Viruses have evolved membrane-restructuring mechanisms for sustaining entry into
      cells, genome replication and release from host cells. Picornavirus 2B, a non
      structural protein required for effective viral replication, functions as a
      potent intracellular pore-forming toxin by altering the permeability of cellular
      endomembranes. Two consecutive hydrophobic regions have been identified in 2B
      protein that could function as an "alpha-helix-turn-alpha-helix" hairpin membrane
      anchor. A peptide derived from the first transmembrane domain comprised a "one
      helix" 2B version that possesses the intrinsic pore-forming activity required to
      directly and effectively permeabilize the cell plasma membrane. Moreover, this
      miniaturized form is capable of translocating through the plasma membrane of
      culture cells and to target mitochondria. These evidences suggest that viroporins
      constitute a new source of membrane-active sequences, worth exploring as
      potential leads for the development of bioactive peptides, and/or as targets for
      the development of antiviral compounds.

PMID- 23131191
TI  - Is there anybody in there? On the mechanisms of wall crossing of cell penetrating
      peptides.
AB  - Cell penetrating peptides (CPPs) belong to the large family of membrane active
      peptides that comprises antimicrobial and viral fusion peptides with whom they
      share many properties. CPPs have been increasingly used to transport a wide range
      of molecules and nanoparticles inside cells. Despite their recognized potential
      transporting properties, their mode of action is far from being understood and
      has been a matter of debate. Penetratin, a widely used CPP is one of the first
      discovered CPPs, yet its mechanism of action remains obscure. Herein an overview
      on studies regarding cellular and liposomal uptake and the interaction with lipid
      model systems of CPPs and more particularly penetratin is provided. Special
      emphasis will be given to biophysical approaches to investigate penetratin/lipid
      interaction and subsequent lipid reorganization using lipid model systems.

PMID- 23131192
TI  - Evaluation of the effect of calcium gluconate and bovine thrombin on the temporal
      release of transforming growth factor beta 1 and platelet-derived growth factor
      isoform BB from feline platelet concentrates.
AB  - BACKGROUND: There are not reported regarding the protocols for obtaining platelet
      concentrates (PC) in cats for medical purposes. The objectives of this study
      were: 1) to describe a manual method for producing two kinds of PC in cats (PC-A
      and PC-B), 2) to describe the cellular population of the PC, 3) to measure and
      compare the effect of calcium gluconate (CG) and bovine thrombin (BT) on the
      temporal release of transforming growth factor beta 1 (TGF-beta1) and platelet
      derived growth factor type BB (PDGF-BB) at 3 and 12 hours post-activation and 4)
      to establish correlations between the cellular population of both PCs and the
      concentration of growth factors (GF). Blood samples were taken from 16 cats for
      complete blood count, plasma collection and PC preparation. The PC were
      arbitrarily divided into two fractions, specifically, PC-A (lower fraction) and
      PC-B (upper fraction). RESULTS: The platelet counts were significantly different
      (P<0.05) between the PC and whole blood but not between the PC fractions. The TGF
      beta1 concentration efficiencies for PC-A and PC-B activated with CG were 42.86%
      and 46.54%, and activated with BT were 42.88% and 54.64%, respectively. The PDGF
      BB concentration efficiencies for PC-A and PC-B activated with CG were 61.36% and
      60.61%, and activated with BT were 65.64% and 72.12%, respectively. The temporal
      release of GFs showed no statistically significant difference (P>0.05) between
      the activating substances at the time or for any PC fraction. CONCLUSIONS:
      Whatever the activation means, these preparations of cat PC provide significant
      concentrations of platelets and GFs for possible clinical or experimental use.

PMID- 23131193
TI  - Third- and fourth-degree perineal tears--incidence and risk factors.
AB  - OBJECTIVE: To assess the incidence and risk factors for third- and fourth-degree
      perineal tears (34DPT), and to identify subgroups of women who are at especially
      high risk for 34DPT. METHODS: A cohort study of women who underwent vaginal
      delivery in a single tertiary medical center between 1999 and 2011, (58 937
      deliveries). Women diagnosed with 34DPT following delivery were compared to
      control group. Multivariate logistic regression analysis and tree classification
      analysis were used to identify combinations of risk factors which were associated
      with considerable risk for 34DPT. RESULTS: Overall, 356 (0.6%) deliveries were
      complicated by 34DPT (340 (95.5%) third-degree tears and 16 (4.5%) fourth-degree
      tears). Independent predictors of 34DPT were: forceps delivery (odds ratio (OR) =
      5.5, confidence interval (CI) 3.9-7.8), precipitate labor (OR = 5.2, CI 2.9-9.2),
      persistent occiput posterior position (OR = 2.6, CI 1.6-4.3), vacuum extraction
      (OR = 1.9, CI 1.4-2.6) as well as large for gestational age (LGA) infant and
      gestational age > 40 weeks. Fourth-degree tears were associated with forceps
      delivery (OR = 12.5, CI 2.3-66.2), precipitate labor (OR = 9.7, 95%-CI 1.2-75.4)
      and LGA infant (OR = 7.4, 95%-CI 1.7 -1.5). Overall, the predictability of 34DPT
      was limited (R(2 )= 0.4). In subgroups of women with certain combinations of risk
      factors the risk of 34DPT ranged from 10% to 25%. CONCLUSION: Despite the limited
      predictability of 34DPT by individual risk factors, the use of combinations of
      risk factors may assist obstetricians in identifying women who are at especially
      high risk for 34DPT.

PMID- 23131194
TI  - Electroanatomic characterization and ablation outcome of nonlesion related left
      atrial macroreentrant tachycardia in patients without obvious structural heart
      disease.
AB  - INTRODUCTION: Descriptions for left atrial macroreentry tachycardia (LAMRT) in
      patients without obvious structural heart disease or previous surgery or catheter
      radiofrequency (RF) ablation have been sparse. METHODS AND RESULTS: Ten of 226
      patients (7 women, mean age 57 +/- 14) with LAMRT underwent electroanatomic
      mapping and catheter ablation. None of the 10 patients had structural heart
      disease or history of previous surgery or catheter ablation. In all patients, the
      reentry circuits were located within a large low-voltage (bipolar voltage <= 0.5
      mV) area in left atrium (LA), which contained 2.6 +/- 1.2 electrically silent
      areas (ESAs) and/or lines of double potentials (LDPs). The tachycardia circuit
      propagated through a narrow isthmus (<5 mm width) bounded by ESAs/LDPs and
      adjacent anatomical barriers (e.g., mitral annulus). In these isthmus, low
      amplitude (0.21 +/- 0.05 mV), long-duration (123 +/- 14 milliseconds)
      fractionated electrograms were found in 8 tachycardias, accounting for 43 +/- 5%
      of the tachycardia cycle length. In 2 other tachycardias without fractionated
      electrograms, the electrogram amplitude in the isthmus was extremely low (<0.1
      mV). RF energy was delivered at the isthmuses and terminated all 10 tachycardias.
      After ablation, the original LAMRT was not inducible in all patients. During
      follow-up (mean 14 +/- 10 months), 2 patients developed recurrence of ATs and
      were successfully ablated. CONCLUSION: Extensive scarring of the LA formed
      arrhythmogenic substrates of LAMRT in this group of patients. Ablation targeting
      these narrow, slow conduction zones eliminated atrial tachycardia in all
      patients.

PMID- 23131195
TI  - Wavelength-dependent absorption in structurally tailored randomly branched
      vertical arrays of InSb nanowires.
AB  - Arrays of semiconductor nanowires are of potential interest for applications
      including photovoltaic devices and IR detectors/imagers. While nominally uniform
      arrays have typically been studied, arrays containing nanowires with multiple
      diameters and/or random distributions of diameters could allow tailoring of the
      photonic properties of the arrays. In this Letter, we demonstrate the growth and
      optical properties of randomly branched InSb nanowire arrays. The structure
      mentioned can be approximated as three vertically stacked regions, with average
      diameters of 20, 100, and 150 nm within the respective layers. Reflectance and
      transmittance measurements on structures with different average nanowire lengths
      have been performed over the wavelength range of 300-2000 nm, and absorbance has
      been calculated from these measurements. The structures show low reflectance over
      the visible and IR regions and wavelength-dependent absorbance in the IR region.
      A model considering the diameter-dependent photonic coupling (at a given
      wavelength) and random distribution of nanowire diameters within the regions has
      been developed. The diameter-dependent photonic coupling results in a roll-off in
      the absorbance spectra at wavelengths well below the bulk cutoff of ~7 MUm, and
      randomness is observed to broaden the absorbance response. Varying the average
      diameters would allow tailoring of the wavelength dependent absorption within
      various layers, which could be employed in photovoltaic devices or wavelength
      dependent IR imagers.

PMID- 23131196
TI  - Enantiomers of an indole alkaloid containing unusual dihydrothiopyran and 1,2,4
      thiadiazole rings from the root of Isatis indigotica.
AB  - A pair of enantiomers (1a and 1b) of an indole alkaloid containing
      dihydrothiopyran and 1,2,4-thiadiazole rings was isolated from an aqueous extract
      of the root of Isatis indigotica. The structures and absolute configurations of
      the enantiomers were determined by extensive spectroscopic analysis, especially
      2D NMR, modified Mosher's method, and electronic CD (ECD). The proposed
      biosynthetic pathway and preliminary investigations of the biological activity of
      compounds 1a and 1b against influenza virus A/Hanfang/359/95 (H3N2) and HSV-1 are
      also discussed.

PMID- 23131197
TI  - Difficult venepuncture--it was all in the head!
AB  - AIM: To emphasise the importance of careful observations and demonstrate that
      significant conditions may, on occasion, be detected during blood donation.
      BACKGROUND: Venepunctures, the bread and butter of blood donor services, can be
      difficult procedures. We describe an unusual presentation of a relatively rare
      disease detected during routine blood donations because of difficult
      venepunctures. METHODS: Case report. RESULTS: A growth hormone-secreting
      pituitary adenoma was diagnosed, and successfully treated, following the initial
      observation of hard-to-puncture skin during blood donations. CONCLUSIONS:
      Seemingly trivial abnormalities may prove clinically important. One presentation
      of acromegaly is hard-to-puncture skin.

PMID- 23131198
TI  - Activity levels of (210)Po and (210)Pb in some fish species of the Izmir Bay
      (Aegean Sea).
AB  - Concentrations of 210Po and 210Pb were determined in the edible muscle tissue of
      twelve species of marine fish collected from Izmir Bay in the Aegean Sea Region
      of Turkey during the 2006-2007. 210Po activity concentrations in fish samples
      were found to vary from ND to 400+/-9 Bq kg-1 dry weight and 210Pb activity
      concentrations were found to vary from ND to 15+/-3 Bq kg-1 dry weight. The
      highest dose contribution due to 210Po to humans was found to be 8.908 MUSv y-1.

PMID- 23131199
TI  - Preventive effects of polyurethane foam and polyvinyl acetate on bleeding and
      pain in young patients undergoing conchotomies.
AB  - OBJECTIVES: The purpose of this prospective study was to determine the
      effectiveness of polyurethane foam (PUF) and polyvinyl acetate (PA) as packing
      materials for reducing post-conchotomy bleeding, pain, and headaches. METHODS:
      This study was a prospective, randomized and single-blinded controlled study.
      Fifty-two patients (5-14 years of age) who underwent conchotomies were enrolled
      in this study. Thirty-two and 20 patients were packed with PUF (group A) and PA
      (group B) after conchotomies, respectively. The occurrence of bleeding after
      removing the packing was checked post-operatively on the fifth or sixth day for
      group A and second day for group B. In addition, other complications, such as
      delayed nasal bleeding after discharge to home, nasal pain following removal of
      the packing, and headaches during insertion of the packing materials in the nasal
      cavities were also noted. RESULTS: No bleeding or mild bleeding occurred when
      aspirating the packing material in group A. In group B, 13 out of 20 patients
      (65%) had severe bleeding and 7 of 20 patients (35%) experienced mild bleeding.
      The bleeding pattern in group B was statistically different from that of group A
      (p<0.05). The number of patients with severe nasal pain during packing removal
      was higher in group B (60%) than group A (3%; p<0.05). The occurrence of
      headaches during nasal packing and delayed bleeding was not statistically
      different between the two groups. CONCLUSIONS: PUF was as effective as PA for
      controlling bleeding after conchotomies, and more effective than PA for
      preventing bleeding and nasal pain when packing was removed from young patients.

PMID- 23131200
TI  - Effects of normal saline and selenium-enriched hot spring water on experimentally
      induced rhinosinusitis in rats.
AB  - OBJECTIVE: This prospective, randomized, and controlled study examined the
      effects of normal saline and selenium-enriched hot spring water on experimentally
      induced rhinosinusitis in rats. METHODS: The study comprised two control groups
      (untreated and saline-treated) and three experimental groups of Sprague Dawley
      rats. The experimental groups received an instillation of lipopolysaccharide
      (LPS) only, LPS+normal saline (LPS/saline), or LPS+selenium-enriched hot spring
      water (LPS/selenium). Histopathological changes were identified using hematoxylin
      eosin staining. Leakage of exudate was identified using fluorescence microscopy.
      Microvascular permeability was measured using the Evans blue dye technique.
      Expression of the Muc5ac gene was measured using reverse transcription-polymerase
      chain reaction. RESULTS: Mucosal edema and expression of the Muc5ac gene were
      significantly lower in the LPS/saline group than in the LPS group. Microvascular
      permeability, mucosal edema, and expression of the Muc5ac gene were significantly
      lower in the LPS/selenium group than in the LPS group. Mucosal edema was similar
      in the LPS/selenium group and LPS/saline group, but capillary permeability and
      Muc5ac expression were lower in the LPS/selenium group. CONCLUSIONS: This study
      shows that normal saline and selenium-enriched hot spring water reduce
      inflammatory activity and mucus hypersecretion in LPS-induced rhinosinusitis in
      rats.

PMID- 23131201
TI  - Prevalence of ventilation tubes in children with a tracheostomy tube.
AB  - OBJECTIVES: To estimate the prevalence of operative ear disease in pediatric
      patients with tracheostomy tubes, as well as to identify risk factors predictive
      of operative otologic interventions in this patient cohort. METHODS: We
      hypothesize that the prevalence of operative middle ear disease in patients with
      a tracheostomy tube is greater than that of the population at large. To validate
      our anecdotal observations, we queried the CHCA hospital database (PHIS)
      regarding the association between tympanostomy tube placements in children with
      tracheostomies. To further investigate, a retrospective chart review was
      undertaken at our regional tertiary care children's hospital to determine the
      frequency at which tympanostomy tubes were placed in children who have a
      tracheostomy. Risk factors were analyzed, applying independent samples t-tests
      and Pearson's Chi-square test. Univariate and multivariate logistic regression
      models were constructed to estimate odds ratios (OR) and 95% confidence intervals
      (CI) for predictors of operative ear disease. Institutional review board (IRB)
      approval was obtained. RESULTS: Of a population of 181 patients with
      tracheostomies, 37 (or 20%, 95% CI 15-26%) have undergone placement of
      ventilation tubes in the past 3 years. No statistically significant difference
      was noted with regards to gender or race. The operative group had an average age
      of 23.0 months at the time of tracheostomy, compared to 52.5 months in the non
      operative group (p=0.0022). In addition, home living situation, term birth, and
      craniofacial abnormalities were more frequently observed in the operative versus
      the non-operative group. Multivariate logistic regression models revealed the
      same factors as predictors of operative ear disease. CONCLUSION: The presence of
      a tracheostomy is associated with an increased risk of requiring ventilation tube
      placement over the population at large. Risk factors for operative middle ear
      disease among these children include age at time of the tracheostomy,
      craniofacial abnormalities, term birth, and home living situation.

PMID- 23131202
TI  - Pregnancy complicated by a severe form of foetal osteogenesis imperfecta in a 17
      year-old primigravida: case report and overview of literature.
AB  - Abstract Osteogenesis imperfecta (OI) is an important inheritable thanetrophic
      disorder with wide ranging variable implications and prognosis for babies in
      utero and those who survive the perinatal period. The diagnosis of the severe
      forms can be readily made but some forms of the disease are known to go
      unrecognised until childhood.

PMID- 23131203
TI  - Mechanism of the ABC transporter ATPase domains: catalytic models and the
      biochemical and biophysical record.
AB  - ABC transporters comprise a large, diverse, and ubiquitous superfamily of
      membrane active transporters. Their core architecture is a dimer of dimers,
      comprising two transmembrane domains that bind substrate and form the channel,
      and two ATP-binding cassettes, which bind and hydrolyze ATP to energize the
      translocase function. The prevailing paradigm for the ABC transport mechanism is
      the Switch Model, in which the nucleotide binding domains are proposed to
      dimerise upon binding of two ATP molecules, and thence dissociate upon sequential
      hydrolysis of the ATP. This idea appears consistent with crystal structures of
      both isolated subunits and whole transporters, as well as with a significant body
      of biochemical data. Nonetheless, an alternative Constant Contact Model has been
      proposed, in which the nucleotide binding domains do not fully dissociate, and
      ATP hydrolysis occurs alternately at each of the two active sites. Here, we
      review the biochemical and biophysical data relating to the ABC catalytic
      mechanism, to show how they may be construed as consistent with a Constant
      Contact Model, and to assess to what extent they support the Switch Model.

PMID- 23131204
TI  - Prospective echocardiographic and tissue Doppler screening of a large Sphynx cat
      population: reference ranges, heart disease prevalence and genetic aspects.
AB  - OBJECTIVES: (1) To investigate heart morphology and function using
      echocardiography and tissue Doppler imaging (TDI), (2) to determine heart disease
      prevalence and characteristics, and (3) to assess potential genetic features in a
      population of Sphynx cats presented for cardiovascular screening. ANIMALS: A
      total of 147 echocardiographic examinations, including 33 follow-ups, were
      performed by trained observers on 114 Sphynx cats of different ages (2.62 +/-
      1.93 years [0.5-10.0]) from 2004 to 2011. METHODS: Sphynx cats underwent a
      physical examination, conventional echocardiography, and, if possible, two
      dimensional color TDI. RESULTS: Conventional echocardiographic findings included
      75/114 normal (65.8%) and 39/114 (34.2%) abnormal examinations with a diagnosis
      of either congenital heart diseases (n = 16) or hypertrophic cardiomyopathy (HCM,
      n = 23). In adult healthy cats, a significant body weight effect was observed for
      several echocardiographic variables, including end-diastolic left ventricular
      (LV) free wall (P < 0.01), interventricular septum (P < 0.001), and LV diameter
      (P < 0.001). Mitral valve dysplasia (MVD) was observed as a single or associated
      defect in 15/16 cats with congenital heart diseases. A significant increase in
      HCM prevalence (P < 0.001) was observed according to age. The pedigree analysis
      of a large family (n = 81) suggested an autosomal dominant mode of inheritance
      with incomplete penetrance for HCM. CONCLUSIONS: Body weight should be taken into
      account when interpreting values of diastolic myocardial wall thicknesses in
      Sphynx cats. Additionally, HCM and MVD are two relatively common heart diseases
      in this feline breed. More pedigree data are required to confirm the inheritance
      pattern of HCM at the breed level.

PMID- 23131205
TI  - InCl3/Me3SiCl-catalyzed direct Michael addition of enol acetates to alpha,beta
      unsaturated ketones.
AB  - The direct Michael addition of enol acetates to alpha,beta-unsaturated ketones
      was achieved using a combination of Lewis acid catalysts, InCl(3) and Me(3)SiCl,
      which furnished stable enol-form products that could be further transformed into
      functionalized 1,5-diketones by reactions with various electrophiles.

PMID- 23131206
TI  - Safety and immunogenicity of a pneumococcal histidine triad protein D vaccine
      candidate in adults.
AB  - BACKGROUND: Pneumococcal vaccines based on conserved protein antigens have the
      potential to offer expanded protection against Streptococcus pneumoniae.
      OBJECTIVE: To explore safety and immunogenicity of a recombinant protein vaccine
      candidate against S. pneumoniae composed of adjuvanted pneumococcal histidine
      triad protein D (PhtD). METHODS: This phase I, exploratory, open-label, single
      center clinical study enrolled adults (18-50 years). Participants in a pilot
      safety cohort received a single intramuscular injection of 6 MUg. Following
      safety review, 3 dose cohorts were enrolled (6, 25, and 100 MUg); participants
      received 2 injections administered approximately 30 days apart. Assignment of the
      second injection and successive dose cohorts were made after blinded safety
      reviews after each injection at each dose level. Safety endpoints included rates
      of solicited injection site and systemic reactions, unsolicited adverse events,
      serious adverse events, and safety laboratory tests. Immunogenicity endpoints
      included levels of anti-PhtD antibodies as measured by ELISA. RESULTS: Sixty
      three participants were enrolled and received the pilot safety dose (n=3) or at
      least 1 dose of PhtD vaccine candidate at 6 MUg (n=20), 25 MUg (n=20), or 100 MUg
      (n=20). No safety concerns were identified. No vaccine-related serious adverse
      event was reported. The most common solicited injection site reaction was pain
      and most common solicited systemic reactions were myalgia and headache; most
      reactions were mild and transient. Observed geometric mean concentrations (95%
      CI) were 200.99 ELISA units (148.46, 272.10), 352.07 (193.49, 640.63), and 699.15
      (405.49, 1205.48) post-injection 1 in the 6, 25, and 100 MUg dose cohorts,
      respectively, and 378.25 (275.56, 519.21), 837.32 (539.29, 1300.04), and 1568.62
      (1082.92, 2272.16) post-injection 2. CONCLUSIONS: All dose levels were safe and
      immunogenic. The frequency of solicited reactions was highest at the 100 MUg
      dose. Administration of a second injection significantly increased the levels of
      anti-PhtD antibodies (ClinicalTrials.gov registry no. NCT01444001).

PMID- 23131207
TI  - Safety and immunogenicity of an adjuvanted whole virion, inactivated A (H1N1)
      2009 influenza vaccine in young and elderly adults, and children.
AB  - An alum adjuvanted whole virion inactivated vaccine against the A (H1N1) 2009
      pandemic virus was developed in India. Two double-blind, randomized studies were
      conducted. Fifty adults (18-50 years) were enrolled in the Phase I study, whereas
      the Phase II/III study consisted of 330 adults (>=18 years) and children >=3
      years. Safety (both studies) and immunogenicity (Phase II/III study) by
      hemagglutination inhibition (HI) antibody titers, of 10 MUg or 15 MUg of
      hemagglutinin (HA) antigen were compared. In the Phase I study, mostly mild and
      transient injection site and systemic reactions were reported. Similar events
      were seen in the Phase II/III study. The overall seroprotection was 96% and 89%
      with 10 and 15 MUg doses, respectively, while the seroconversion was 92% and 88%.
      The new Indian-made pandemic H1N1 vaccine is safe and immunogenic in adults and
      children above 3 years of age.

PMID- 23131208
TI  - Is poor research the cause of the declining productivity of the pharmaceutical
      industry? An industry in need of a paradigm shift.
AB  - For the past 20 years target-based drug discovery has been the main research
      paradigm used by the pharmaceutical industry and billions of dollars have been
      invested into this approach. However, recent industry data strongly indicate that
      the target-based approach is not an effective drug discovery paradigm and is
      likely to be the cause of the productivity crisis the industry is experiencing.
      However, from a theoretical and scientific perspective the target-based approach
      appears sound, so why is it not more successful? The purpose of this paper is
      first to analyse the real-life implementation of the target-based approach to
      identify possible reasons for the high failure rate and second to suggest changes
      to the drug discovery approach, which can improve productivity.

PMID- 23131209
TI  - Development and utilization of a bovine type I collagen microfibril model.
AB  - The structure of fibrous collagen, a long triple helix that self-associates in a
      staggered array to form a matrix of fibrils, fibers and fiber bundles, makes it
      uniquely suitable as a scaffold for biomaterial engineering. A major challenge
      for this application is to stabilize collagen structure by means that are
      acceptable for the end use. The bovine type I collagen microfibril model, built
      by computer assisted modeling, comprised of five right-handed triple helices in a
      left-handed super coil containing gap and overlap regions as well as the
      nonhelical telopeptides is a tool for predicting or visualizing chemistry to
      stabilize the matrix, insert an active agent, or otherwise modify collagen.

PMID- 23131210
TI  - Management of iatrogenic full thickness electrical burn in a preterm neonate
      using W-plasty technique combined with a median sternotomy incision.
AB  - Burns in the neonatal period are rare and most commonly due to iatrogenic causes.
      We report a case of a preterm neonate who sustained a full thickness electrical
      burn following the use of a temporary pacing pad. The case was complicated by
      significant co-morbidities and the need for  cardiac surgery. We describe the
      surgical management of the case, using excision and closure in the form of a W
      plasty. We discuss the reasons for this surgical decision and the importance of
      managing complex cases such as this on an individual basis.

PMID- 23131211
TI  - Stapled diverticulectomy for solitary caecal diverticulitis.
AB  - Caecal diverticulitis is an uncommon phenomenon in western countries. The
      clinical diagnosis is often difficult as it mimics other acute abdominal
      conditions like appendicitis, colitis or neoplasia. Diagnosis is often made at
      operation. Operative strategy has been controversial and  there is no broad
      consensus emerging. We report the case of a 71-year-old woman, known to have
      chronic obstructive pulmonary disease, who presented acutely with right iliac
      fossa pain. A clinical diagnosis of appendicitis was made. At laparoscopy, a
      solitary, inflamed, gangrenous caecal diverticulum  was found. A laparoscopic
      stapled diverticulectomy was performed. The patient made a steady post-operative
      recovery. Histology confirmed diverticulitis. We conclude that stapled
      diverticulectomy for solitary caecal diverticulitis is a safe and effective
      surgical strategy when confronted with  this scenario.

PMID- 23131212
TI  - Abdominal compartment syndrome caused by tension pneumoperitoneum in a scuba
      diver.
AB  - Abdominal compartment syndrome is a surgical emergency caused by a raised intra
      abdominal pressure, which may lead to respiratory, cardiovascular and renal
      compromise. It is most commonly seen in post-operative and trauma patients and it
      has a variety of causes. Tension pneumoperitoneum  (TP) is a rare cause of
      abdominal compartment syndrome most often seen after gastrointestinal endoscopy
      with perforation.  We present the case of a fit 52-year-old experienced female
      diver who developed TP and shock following a routine training dive to 27m.
      Following accidental inhalation  of water, she had an unstaged ascent and, on
      reaching the surface, developed severe acute abdominal pain and distension. She
      was brought to our emergency department by air ambulance for assessment. Clinical
      and radiological examination revealed a shocked patient with dramatic free intra
      abdominal  gas and signs of abdominal compartment syndrome, which was treated
      with needle decompression. Symptoms and signs resolved quickly with no need for
      further surgical intervention. TP is a surgical emergency where surgery can be
      avoided with prompt diagnosis and treatment.

PMID- 23131213
TI  - Managing chondrosarcoma of the epiglottis: a case report.
AB  - Laryngeal chondrosarcomas are a very rare malignancy with less than 150 cases
      reported in the literature. Of these, the epiglottis is the most unusual primary
      neoplastic subsite. Uncertainties arise owing to the extremely rare nature of the
      condition with regard to treatment and investigation  for metastases in overtly
      low grade cases. We present the case of a 62-year-old woman with a low grade
      chondrosarcoma, arising from the tip of the epiglottis, presenting with dysphagia
      but no other symptoms.

PMID- 23131214
TI  - Spontaneous pneumomediastinum presenting as rhinolalia and chest pain.
AB  - This report discusses a case of spontaneous pneumomediastinum in a 25-year-old
      medical student. The patient presented with chest pain and a tonal change in
      voice. Symptoms occurred after an episode of stretching and were exacerbated by
      coughing. There was no history of underlying respiratory  disease and he was a
      non-smoker. Management was conservative. At the four-week follow-up appointment,
      bronchoscopy and computed tomography of the thorax demonstrated complete
      resolution. Spontaneous pneumomediastinum is uncommon, with rhinolalia being a
      rare presenting feature. It should be  considered as a differential diagnosis in
      patients with chest pain associated with a change in voice. A detailed history
      may reveal preceding activities associated with raised intrathoracic pressure.

PMID- 23131215
TI  - Spontaneously perforated pyometra: an unusual cause of acute abdomen and
      pneumoperitoneum.
AB  - Pneumoperitoneum is usually associated with gastrointestinal perforation or
      following surgical and endoscopic procedures. We report a rare case of
      spontaneously perforated pyometra presenting with generalised peritonitis and
      pneumoperitoneum. Perforation of the uterus is also unusual  and often associated
      with the presence of an intrauterine device, a gravid uterus or malignancy. Our
      case illustrates the importance of clinical knowledge of acute and neoplastic
      gynaecological diseases, which are not uncommonly encountered by the general
      surgeon. Moreover, good appreciation  of pelvic anatomy and close collaboration
      with gynaecology colleagues is essential as operative intervention is often
      required.

PMID- 23131216
TI  - Metabolic acidosis: neo-considerations for general surgeons.
AB  - Hyperchloraemic metabolic acidosis is a documented complication of neobladder
      formation. However, it usually improves with time and is mild. Severe and
      persistent metabolic acidosis may manifest when patients undergo further surgery
      for other reasons. Neobladder formation following  radical cystectomy or
      cystoprostatectomy is becoming increasingly common, and surgeons treating
      patients with neobladders should recognise and treat metabolic acidosis with
      intravenous fluids and bicarbonate.

PMID- 23131217
TI  - Ectopic Cushing's syndrome due to a mesenteric neuroendocrine tumour.
AB  - INTRODUCTION: Neuroendocrine tumours (NETs) are tumours that commonly involve the
      gastrointestinal system. Common primary sites in the gastrointestinal system
      include the small intestine, appendix, rectum and pancreas. Mesenteric NETs are
      extremely rare entities and are sparsely reported  in the literature. CASE
      HISTORY: We report the case of a 62-year-old woman with ectopic Cushing's
      syndrome due to excessive adrenocorticotropic hormone secretion by a primary
      mesenteric tumour in the small intestine and its liver metastases. CONCLUSIONS:
      Although rare, the mesentery  can be a primary site for NETs. It can cause
      similar symptoms and require similar treatment options. Tumour resection and
      debulking are acceptable ways to improve both the survival and symptoms.

PMID- 23131218
TI  - Reconstruction of the pelvis and perineum with a free latissimus dorsi
      myocutaneous flap: a case report.
AB  - Reconstruction of the perineum and pelvic cavity in continuity is an uncommon and
      difficult challenge. This case describes a 66-year-old man who presented
      following recurrence of a Dukes' B rectosigmoid adenocarcinoma that had been
      treated nine years previously by anterior resection,  5-fluorouracil and
      radiotherapy. His recurrent disease was treated with radical pelvic exenteration
      with formation of an end colostomy and urinary ileal conduit.  A post-operative
      pelvic collection necessitated incisional drainage via the perineum. This
      resulted in a perineal defect in  continuity with the pelvic cavity, neither of
      which healed in spite of alternate day packing with antiseptic dressings. The
      perineum and cavity were reconstructed successfully with a microvascular transfer
      of the latissimus dorsi using the primary gracilis pedicle as recipient donor
      vessels.

PMID- 23131219
TI  - Anterior cruciate ligament reconstruction complicated by pyoderma gangrenosum.
AB  - We report a case of pyoderma gangrenosum as a complication of an anterior
      cruciate ligament reconstruction in a patient with inflammatory bowel disease,
      which was misdiagnosed initially as a post-operative wound infection. An early
      dermatology opinion and skin biopsy should be considered  in cases of suspected
      infection where thorough surgical debridement and antimicrobial therapy has
      failed to improve the clinical picture.

PMID- 23131220
TI  - Surgical research and activity analysis using Hospital Episode Statistics.

PMID- 23131221
TI  - Plantar fasciitis.
AB  - INTRODUCTION: In this article we look at the aetiology of plantar fasciitis, the
      other common differentials for heel pain and the evidence available to support
      each of the major management options. We also review the literature and discuss
      the condition. METHODS: A literature search  was performed using PubMed and
      MEDLINE((r)). The following keywords were used, singly or in combination:
      'plantar fasciitis', 'plantar heel pain', 'heel spur'. To maximise the search,
      backward chaining of reference lists from retrieved papers was also undertaken.
      FINDINGS: Plantar  fasciitis is a common and often disabling condition. Because
      the natural history of plantar fasciitis is not understood, it is difficult to
      distinguish between those patients who recover spontaneously and those who
      respond to formal treatment. Surgical release of the plantar fascia is effective 
      in the small proportion of patients who do not respond to conservative measures.
      New techniques such as endoscopic plantar release and extracorporeal shockwave
      therapy may have a role but the limited availability of equipment and skills
      means that most patients will continue to be treated  by more traditional
      techniques.

PMID- 23131222
TI  - Questionable safety of thyroid surgery with same day discharge.
AB  - INTRODUCTION: Over the last two decades increasing numbers of surgical procedures
      have been performed on an outpatient basis. In 2000 the National Health Service
      in England set the target of performing 75% or more of all elective surgical
      procedures as day cases and in 2001 the British  Association of Day Surgery added
      thyroidectomy to the list of day case procedures. However, same day discharge
      following thyroidectomies has been adopted by only a very small number of UK
      centres. The aim of this review was to establish the evidence base surrounding
      same day discharge thyroid  surgery. METHODS: The British Association of
      Endocrine and Thyroid Surgeons commissioned the authors to perform a review of
      the best available evidence regarding day case thyroid surgery as a part of a
      consensus position to be adopted by the organisation. A MEDLINE((r))review  of
      the English medical literature was performed and the relevant articles were
      collated and reviewed. RESULTS: There are limited comparative data on day case
      thyroid surgery. It is feasible and may save individual hospitals the cost of
      inpatient stay. However, the risk of airway compromising  and life threatening
      post-operative bleeding remains a major concern since it is not possible to
      positively identify those patients most and least at risk of bleeding after
      thyroidectomy. It is estimated that half of all post-thyroidectomy bleeds would
      occur outside of the hospital environment  if patients were discharged six hours
      after surgery. CONCLUSIONS: Same day discharge in a UK setting cannot be
      endorsed. Any financial benefits may be outweighed by the exposure of patients to
      an increased risk of an adverse outcome. Consequently, 23-hour surgery is
      recommended.

PMID- 23131223
TI  - Delayed presentation of vernix caseosa peritonitis.
AB  - INTRODUCTION: Vernix caseosa peritonitis (VCP) is a rare and poorly recognised
      condition resulting from a sustained foreign body reaction to the vernix caseosa
      of the baby. This case-based review aims to highlight its importance for any
      medical team managing patients with peritonitis  who have undergone a recent
      Caesarean section. CASE REPORT: A 31-year-old woman presented 5 weeks after a
      Caesarean section with symptoms and signs of peritonitis. CONCLUSIONS: Laparotomy
      and peritoneal lavage is the mainstay of treatment for VCP. Knowledge of the
      condition may stop  inadvertent resection of normal intra-abdominal organs.
      Greater awareness of VCP is required to ensure earlier recognition as patients
      can recover well following timely operative intervention.

PMID- 23131224
TI  - Breast reconstruction with deep inferior epigastric perforator flaps.
AB  - INTRODUCTION: Approximately 45,000 women are diagnosed with breast cancer in the
      UK each year. The success of screening and the introduction of adjuvant therapies
      have meant that prognosis is improving and an increasing number of patients are
      seeking reconstruction following mastectomy.  The purpose of this study was to
      evaluate the deep inferior epigastric perforator (DIEP) flap reconstructions
      performed in Stoke Mandeville Hospital and, through analysis of complications,
      detail the evolution of the current care pathway. METHODS: A retrospective
      analysis was performed  of all the DIEP flap reconstructions performed by the
      senior author (MT) between July 2003 and December 2010. RESULTS: Overall, 159
      flaps were performed on 141 patients (including 36 bilateral flaps). The average
      patient age was 49 years (range: 28-70 years) and 13% of flaps were  risk
      reducing for BRCA1/2. Twenty-six per cent of patients suffered one or more
      complication post-operatively, including systemic complications (pulmonary
      embolism 2%) and flap specific complications (partial flap necrosis 9%,
      reanastomosis 3%, fat necrosis 9%). Seventy-four per cent had further  elective
      operations including nipple reconstruction (72%), contralateral breast reduction
      (36%) and scar revision (21%). CONCLUSIONS: DIEP flaps are a safe and reliable
      option for breast reconstructions. This series illustrates the significant
      leaning curve, with complications, operative  time and ischaemic time reducing
      through the series and post-operative haemoglobin increasing. The complications
      experienced in this series of 159 flaps with no total flap loss provide the
      framework for the evolution of the current care pathway including pre-operative
      imaging, peri-operative  deep vein thrombosis prophylaxis and analgesia.

PMID- 23131225
TI  - Patterns of hospital admission with epistaxis for 26,725 patients over an 18-year
      period in Wales, UK.
AB  - INTRODUCTION: Epistaxis is the one of the most common otorhinolaryngology
      emergencies. This study examined the age and sex distribution of all patients
      admitted with epistaxis to National Health Service (NHS) hospitals in Wales, UK,
      over a period of 18 years and 9 months. METHODS: The Patient Episode Database for
      Wales was examined for all patient admissions with a diagnosis of epistaxis
      between April 1991 and December 2009. The age and sex of these patients was
      recorded and the proportion of the underlying population affected was calculated
      by comparing admission rates  to the population data derived from the 1991 and
      2001 national population censuses for Wales. RESULTS: A total of 26,725 patients
      were admitted to NHS hospitals in Wales with epistaxis over the period studied.
      The proportion of the population admitted with epistaxis increased from the  age
      of 40 onwards. For all ages except patients in the 10-14 years group, a higher
      proportion of the male population was admitted with epistaxis than the comparable
      female population. This discrepancy was most pronounced between the ages of 15
      and 49 years, with the female-to-male ratio  of hospital admissions with
      epistaxis being 0.55. These ages (15 and 49 years) approximate the average age of
      menarche and menopause respectively in the UK. CONCLUSIONS: Women of menstrual
      age have fewer hospital admissions with epistaxis. This may be due to oestrogens
      providing protection  to the nasal vasculature (as they do to other areas of the
      vascular tree).

PMID- 23131226
TI  - Double bypass for inoperable pancreatic malignancy at laparotomy: postoperative
      complications and long-term outcome.
AB  - INTRODUCTION: Between 4% and 13% of patients with operable pancreatic malignancy
      are found unresectable at the time of surgery. Double bypass is a good option for
      fit patients but it is associated with a high risk of postoperative
      complications. The aim of this study was to identify  pre-operatively which
      patients undergoing double bypass are at high risk of complications and to assess
      their long-term outcome. METHODS: Of the 576 patients undergoing pancreatic
      resections between 2006 and 2011, 50 patients who underwent a laparotomy for a
      planned pancreaticoduodenectomy  had a double bypass procedure for inoperable
      disease. Demographic data, risk factors for postoperative complications and pre
      operative anaesthetic assessment data including the Portsmouth Physiological and
      Operative Severity Score for the enUmeration of Mortality and morbidity (P
      POSSUM) and  cardiopulmonary exercise testing (CPET) were collected. RESULTS:
      Fifty patients (33 men and 17 women) were included in the study. The median
      patient age was 64 years (range: 39-79 years). The complication rate was 50% and
      the in-hospital mortality rate was 4%. The P-POSSUM physiology  subscore and low
      anaerobic threshold at CPET were significantly associated with postoperative
      complications (p =0.005 and p =0.016 respectively) but they were unable to
      predict them. Overall long-term survival was significantly shorter in patients
      with postoperative complications  (9 vs 18 months). Postoperative complications
      were independently associated with poorer long-term survival (p =0.003, odds
      ratio: 3.261). CONCLUSIONS: P-POSSUM and CPET are associated with postoperative
      complications but the possibility of using them for risk prediction requires 
      further research. However, postoperative complications following double bypass
      have a significant impact on long-term survival and this type of surgery should
      therefore only be performed in specialised centres.

PMID- 23131227
TI  - Prophylactic mesh placement of permanent stomas at index operation for colorectal
      cancer.
AB  - INTRODUCTION: Parastomal herniation occurs in 30-50% of colostomy formations. The
      aim of this study was to radiologically evaluate the mechanical defects at stoma
      sites in patients who had previously undergone a permanent colostomy with or
      without mesh at the index operation for  colorectal cancer. METHODS: A study was
      performed of all colorectal cancer patients (n=41) having an end colostomy
      between 2002 and 2010, with or without Prolene((r)) mesh plication, with blinded
      evaluation of the annual follow-up staging computed tomography (CT) for  stomal
      characteristics. The presence of parastomal hernias, volume, dimensions, grade of
      the parastomal hernia and abdominal wall defect size were measured by two
      independent radiologists, and compared with demographic and operative variables.
      RESULTS: In those patients with radiological  evidence of a parastomal hernia,
      Prolene((r)) mesh plication significantly reduced the incidence of bowel
      containing parastomal hernias at one year following the procedure (p<0.05) and
      also reduced the diameter of the abdominal wall defect (p=0.006). CONCLUSIONS:
      Prophylactic mesh placement at the time of the index procedure reduces the
      diameter of abdominal wall aperture and the incidence of parastomal hernias
      containing bowel. Future studies should use both objective radiological as well
      as clinical endpoints when assessing parastomal hernia development  with and
      without prophylactic mesh.

PMID- 23131228
TI  - Management of colorectal polyp cancers.
AB  - INTRODUCTION: Management of malignant colorectal polyps is controversial. The
      options are resection or surveillance. Resection margin status is accepted as an
      independent predictor of adverse outcome. However, the rate of adverse outcome in
      polyps with a resection margin of <1mm  has not been investigated. METHODS: A
      retrospective search of the pathology database was undertaken. All polyp cancers
      were included. A single histopathologist reviewed all of the included polyp
      cancers. Polyps were divided into three groups: clear resection margin, involved
      resection  margin and unknown resection margin. Polyps were also analysed for
      tumour grade, morphology, Haggitt/Kikuchi level and lymphovascular invasion.
      Adverse outcome was defined as residual tumour at the polypectomy site and/or
      lymph node metastases in the surgical group and local or distant recurrence  in
      the surveillance group. RESULTS: Sixty-five polyps (34 male patients, mean age:
      73 years, range: 50-94 years) were included. Forty-six had clear polyp resection
      margins; none had any adverse outcomes. Sixteen patients had involved polyp
      resection margins and twelve of these underwent  surgery: seven had residual
      tumour and two of these patients had lymph node metastases. Four underwent
      surveillance, of whom two developed local recurrence. Three patients had
      resection margins on which the histopathologist was unable to comment. All
      patients with a clear resection margin  had no adverse outcome regardless of
      other predictive factors. CONCLUSIONS: Polyp cancers with clear resection
      margins, even those with <1mm clearance, can be treated safely with surveillance
      in our experience. Polyp cancers with unknown or involved resection margins
      should be treated  surgically.

PMID- 23131229
TI  - The impact of systemic fungal infection in patients with perforated oesophagus.
AB  - INTRODUCTION: Perforated oesophagus is a surgical emergency with significant
      morbidity and mortality. Systemic fungal infection represents a poor response to
      the magnitude of the insult, which adds significantly to the risk of morbidity
      and mortality in these patients. We reviewed our  experience with this group of
      patients over a six-year period in a tertiary referral centre. METHODS: A
      retrospective clinical review was conducted of patients who were admitted
      following a ruptured oesophagus over a period of six years (January 2002 -
      January 2008). RESULTS: We had 27 admissions (18 men and 9 women) following an
      isolated perforated oesophagus to our unit. The median patient age was 65 years
      (range: 22-87 years). The majority (n=24, 89%) presented with spontaneous
      perforations (Boerhaave's syndrome) and three (11%) were iatrogenic.  Fungal
      organisms, predominantly Candida albicans, were positively cultured in pleural or
      blood samples in 16 (59%) of the 27 patients. Fourteen patients grew yeasts
      within the first seven days while two showed a delayed growth after ten days.
      Overall mortality was 5 out of 27 patients  (19%). There was no mortality among
      the group that did not grow yeasts in their blood/pleural fluid while mortality
      was 31% (5/16) in the group with systemic fungal infection (p<0.001). A positive
      fungal culture was also associated with increase ventilation time, intensive care
      unit  stay and inpatient hospital stay but not an increased rate of
      complications. CONCLUSIONS: Systemic fungal infection in patients with a ruptured
      oesophagus affects a significant proportion of these patients and carries a poor
      prognosis despite advanced critical care interventions. It may  represent a
      general marker of poor host response to a major insult but can add to mortality
      and morbidity. It is worth considering adding antifungal therapy empirically at
      an early stage to antimicrobials in patients with an established diagnosis of a
      perforated oesophagus.

PMID- 23131230
TI  - How safe is diathermy in patients with cochlear implants?
AB  - INTRODUCTION: Cochlear implants are surgically inserted electrical devices that
      enable severely or profoundly deaf individuals to interpret sounds from their
      environment and communicate more effectively. As a result of their electrical
      nature, they are susceptible to electromagnetic  interference and can be damaged
      by excessive electrical energy. Surgical diathermy is one source of such
      potentially damaging energy. The British Cochlear Implant Group guidelines advise
      that monopolar diathermy should not be used in the head and neck region in
      patients with cochlear implants  and that bipolar diathermy should not be used
      within 2cm of the implant
      (http://www.bcig.org.uk/site/public/current/safety.htm). METHODS: A questionnaire
      was provided to 36 surgeons working in different specialties in the head and neck
      region, inquiring as to their knowledge of the safety  considerations when using
      diathermy in cochlear implant patients. Thirty-five surgeons provided responses.
      RESULTS: Overall, 77% of the respondents were unaware of the existence of
      published guidelines. Even when given an option to seek advice, 11% erroneously
      felt it was safe to use monopolar  diathermy above the clavicles with a cochlear
      implant in situ and 49% felt that there was no restriction on the use of bipolar
      diathermy. CONCLUSIONS: There is a significant deficit in the knowledge of safe
      operating practice in the rapidly expanding population of patients with cochlear 
      implants which threatens patient safety. Through this publication we aim to
      increase awareness of these guidelines among members of the surgical community
      and this paper is intended to act as a point of reference to link through to the
      published safety guidelines.

PMID- 23131231
TI  - Safety and efficacy of percutaneous nephrolithotomy for the treatment of
      paediatric urolithiasis.
AB  - INTRODUCTION: Paediatric percutaneous nephrolithotomy (PCNL) has revolutionised
      the treatment of paediatric nephrolithiasis. Paediatric PCNL has been performed
      using both adult and paediatric instruments. Stone clearance rates and
      complications vary according to the technique used and  surgeon experience. We
      present our experience with PCNL using adult instruments and a 28Fr access tract
      for large renal calculi in children under 18 years. METHODS: All patients
      undergoing PCNL at our institution between 2000 and 2009 were reviewed.
      Demographics, surgical details and post-operative  follow-up information were
      obtained to identify stone clearance rates and complications. RESULTS: PCNL was
      performed in 32 renal units in 31 patients (mean age: 10.8 years). The mean stone
      diameter was 19mm (range: 5-40mm). Twenty-six cases required single puncture and
      six required  multiple tracts. Overall, 11 staghorn stones, 10 multiple calyceal
      stones and 11 single stones were treated. Twenty-seven patients (84%) were
      completely stone free following initial PCNL. Two cases had extracorporeal shock
      wave lithotripsy for residual fragments, giving an overall stone free  rate of
      91% following treatment. There was no significant bleeding or sepsis encountered
      either during the operation or in the post-operative setting. No patient required
      or received a blood transfusion. CONCLUSIONS: Paediatric PCNL can be performed
      safely with minimal morbidity using  adult instruments for large stone burden,
      enabling rapid and complete stone clearance.

PMID- 23131232
TI  - The use of locking plates in complex midfoot fractures.
AB  - INTRODUCTION: Complex fracture dislocations of the midfoot are uncommon. Improved
      outcomes have been demonstrated where it has been possible to restore and
      maintain the length and alignment of the medial column as well as the congruity
      of the articular surfaces. We present our experience  with the use of angle
      stable locking plates in the stabilisation of complex midfoot fracture
      dislocations. METHODS: Twelve patients were identified on a prospective trauma
      database between 2003 and 2009. All fractures involved the medial column with
      four associated fracture subluxations  of the lateral column also. Patients
      underwent open reduction internal fixation (ORIF) with restoration of the medial
      column axis, reduction of the articular surface congruity and stabilisation with
      angle-stable locking plates. RESULTS: There were no post-operative infections or
      neurological  injuries. Ten of the twelve patients required metalwork removal.
      There were no implant failures prior to removal of the metalwork. At a mean
      follow-up of 12.4 months (range: 4-32 months), 11 patients had minimal symptoms
      of swelling, discomfort or stiffness in the midfoot. This did not  restrict their
      daily activities. One patient developed post-traumatic arthritis and collapse of
      the medial longitudinal arch. Two patients declined removal of the metalwork.
      CONCLUSIONS: Angle-stable locking plates provide satisfactory stabilisation
      following ORIF of complex midfoot fracture  dislocations. Most patients will
      require removal of the metalwork. Following removal of metalwork, the majority of
      patients will maintain the length, alignment and stability of the midfoot.

PMID- 23131233
TI  - Safe percutaneous suprapubic catheterisation.
AB  - INTRODUCTION: We describe our technique of percutaneous suprapubic catheter
      insertion with special reference to steps that help to avoid common complications
      of haematuria and catheter misplacement. METHODS: The procedure is performed
      using a stainless steel reusable trocar under  local infiltrative anaesthesia,
      usually at the bedside. After clinical confirmation of a full bladder, the trocar
      is advanced into the bladder through a skin incision. Once the bladder is
      entered, the obturator is removed and the assistant inserts a Foley catheter
      followed by rapid balloon  inflation. Slight traction is applied to the catheter
      for about five minutes. Patients with previous lower abdominal surgery, an
      inadequately distended bladder or acute pelvic trauma do not undergo suprapubic
      catheterisation using this method. RESULTS: The procedure was performed in 72 
      men (mean age: 42.4 years, range: 18-78 years) with urinary retention with a
      palpable bladder. The average duration of the procedure was less than five
      minutes. No complications were noted in any of the patients. CONCLUSIONS: Trocar
      suprapubic catheter insertion is a safe and effective  bedside procedure for
      emergency bladder drainage and can be performed by resident surgeons. The common
      complications associated with the procedure can be avoided with a few careful
      steps.

PMID- 23131234
TI  - Removal of AO unreamed tibial nail with a threaded rod from the Taylor Spatial
      Frame.

PMID- 23131235
TI  - X-ray evaluation of failed unicompartmental knee replacement.

PMID- 23131236
TI  - A simple tip to improve the accuracy of crossed K-wire placement in the
      management of displaced paediatric supracondylar fractures of the humerus.

PMID- 23131237
TI  - Foleys protection caps: inexpensive alternative in Ilizarov fixation.

PMID- 23131238
TI  - Posterior to anterior distal locking of humeral intramedullary nails.

PMID- 23131239
TI  - A novel technique to maintain a closed reduction of metacarpal fractures.

PMID- 23131240
TI  - Using chlorhexidine soap as an alternative lubricant for harvesting split skin
      grafts.

PMID- 23131241
TI  - A novel way to remove a broken intramedullary nail.

PMID- 23131242
TI  - Combined laparoscopic cholecystectomy and incisional hernia repair: a proposal
      for standardised technique.

PMID- 23131243
TI  - Closed reduction of Pilon fractures using an ankle distractor to allow for
      minimally invasive fixation.

PMID- 23131244
TI  - A trick for visualisation of the radial tuberosity in a biceps tendon repair.

PMID- 23131245
TI  - A free 'app' for plastic surgery: the smartphone spirit level.

PMID- 23131246
TI  - 'Stop going off on a tangent': a novel method for discriminating pathological
      from tangential fluorescence during photodynamic diagnosis cystoscopy.

PMID- 23131247
TI  - Distal femoral replacement for a periprosthetic fracture: a method for removing
      the distal fragment.

PMID- 23131249
TI  - Better to modify the EWTD than go to India for surgical experience.

PMID- 23131250
TI  - Challenging trials.

PMID- 23131251
TI  - Working with workplaces for TB care and control.

PMID- 23131252
TI  - Recent trends in respiratory mortality in Sao Paulo, Brazil.

PMID- 23131253
TI  - A rational vaccine pipeline for tuberculosis.
AB  - The development of tuberculosis (TB) vaccines is at a turning point, with the
      promise of new vaccines on the horizon. Over the next few years, it is possible
      that we will see a phase III multi-site clinical trial of at least one new TB
      vaccine and perhaps the introduction of a TB vaccine  by the end of the decade.
      However, many gaps remain in our understanding of TB pathogenesis as well as the
      host immune responses required to provide protective immunity. A major challenge
      for TB vaccines is to establish a correlate of vaccine immunity which would
      greatly facilitate bridging  studies needed to approve, license and distribute
      new TB vaccines in all areas endemic for TB. This will require TB vaccines that
      are both safe and effective in all populations. It cannot be accomplished without
      hard work as well as additional resources that match the ambitious goals of the 
      TB community.

PMID- 23131254
TI  - CYP2E1 RsaI/PstI polymorphism and risk of anti-tuberculosis drug-induced liver
      injury: a meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: A number of studies have evaluated the association
      between cytochrome P450 2E1 (CYP2E1) RsaI/PstI polymorphism and the risk of anti
      tuberculosis drug-induced liver injury (ATDILI). However, the results were
      inconsistent. We conducted a meta-analysis  to clarify the role of this
      polymorphism in ATDILI. DESIGN: Two authors independently searched the PubMed,
      Medline, EMBASE and Chinese National Knowledge Infrastructure databases for
      studies on the association of CYP2E1 RsaI/PstI polymorphism with risk of ATDILI.
      Summary odds ratios  (ORs) with their corresponding 95% confidence intervals
      (CIs) were calculated. RESULTS: The combined results showed that the CYP2E1 c1/c1
      genotype was associated with increased ATDILI risk compared to variant genotypes
      (c1/c2+c2/c2) (OR 1.36, 95%CI 1.09-1.69). When stratifying  for study population,
      statistically significant results were observed in Chinese (OR 1.47, 95%CI 1.12
      1.92) and Korean populations (OR 1.85, 95%CI 1.04-3.30). In comparison with
      CYP2E1 c1/c2 or c2/c2 with rapid/intermediate acetylators, the risk of ATDILI
      increased from  1.88 (95%CI 1.14-3.09) for CYP2E1 c1/c1 with rapid/intermediate
      acetylators to 6.44 (95%CI 3.47-11.97) for CYP2E1 c1/c1 with slow acetylators.
      CONCLUSION: This meta-analysis suggests that CYP2E1 RsaI/PstI polymorphism may
      affect susceptibility to ATDILI,  particularly among Chinese and Korean
      populations.

PMID- 23131255
TI  - Lessons from a randomised clinical trial for multidrug-resistant tuberculosis.
AB  - BACKGROUND: The treatment of multidrug-resistant tuberculosis (MDR-TB) is
      currently based upon expert opinion and findings from case series, rather than
      upon randomised clinical trials (RCTs). OBJECTIVE: To describe the challenges
      encountered during an RCT for the treatment of MDR-TB. METHODS: Tuberculosis
      Trials Consortium Study 30 was a pilot, Phase I/II, double-blind, placebo
      controlled, RCT of the safety and tolerability of 16 weeks of daily, low-dose
      linezolid treatment for MDR-TB. RESULTS: A total of 36 patients, 56% of the
      target of 64 patients, consented to participate,  for an average of 0.69
      enrolments per week. Of the 36 patients enrolled, only 25 (69%) completed at
      least 90 doses of study treatment. Among the 12 (33%) patients who did not
      complete all 112 doses of the study treatment, the median time to study
      withdrawal was 15 days (range 0-92).  After the study, we discovered discordance
      between treatment assignment and study drug for at least 9 (25%) of the 36
      patients. CONCLUSIONS: Recruitment and retention in this MDR-TB clinical trial
      posed substantial challenges, suggesting the need for a large, multidisciplinary
      group of  study staff to support the participants. Withdrawal tended to occur
      early in study treatment. The discrepancy in assigned study medication reflects
      the need for stronger administrative controls for study drugs.

PMID- 23131256
TI  - Risk factors for Mycobacterium tuberculosis infection in Indonesian children
      living with a sputum smear-positive case.
AB  - SETTING AND OBJECTIVES: Young children living with infectious tuberculosis (TB)
      cases are at high risk of infection and disease, and screening is recommended.
      This is rarely conducted in resource-limited settings. Identifying children most
      at risk of infection may be useful for setting practical screening policies.
      DESIGN: Child contacts of smear-positive adult TB patients were invited for
      Mycobacterium tuberculosis infection and disease screening by symptoms,
      tuberculin skin test (TST), QuantiFERON-TB Gold In-Tube assay (QFT-GIT) and chest
      X-ray. Risk factors for infection were collected using a questionnaire and were
      calculated separately for TST, for QFT-GIT and for both tests combined. RESULTS:
      Of 304 screened children 145/302 (48%) were positive using TST, 152/299 (51%) by
      QFT-GIT and 180/304 (59%) were positive using either or both tests. Positivity
      for both tests was associated with index case infectivity (acid-fast bacilli
      [AFB] 3+ vs. AFB 1+: TST OR 2.93, 95%CI 1.59-5.39; QFT-GIT OR 2.28, 95%CI 1.06
      4.90) and exposure (child contact's parent is the index case: TST OR 7.04, 95%CI
      2.23-22.28; QFT-GIT OR 4.30, 95%CI 1.48-12.45). CONCLUSION: M. tuberculosis
      infection according to either test was high, supporting screening and preventive
      treatment. Children of smear-positive TB cases who accompany their parents to the
      clinic should be prioritised for immediate screening.

PMID- 23131257
TI  - Implementation of tuberculosis infection control measures at HIV care and
      treatment sites in sub-Saharan Africa.
AB  - SETTING: A total of 663 human immunodeficiency virus (HIV) care and treatment
      sites in nine tuberculosis (TB) affected African countries, serving over 900,000
      persons living with HIV. OBJECTIVE: To determine the implementation of infection
      control (IC) measures and whether program and facility characteristics were
      associated with implementation of these measures. DESIGN: A survey was conducted
      to assess the presence of a TB IC plan, triage practices for TB suspects,
      location of sputum collection and availability of particulate respirators. The
      association of facility characteristics with IC measures was examined using
      bivariate and multivariate methods. RESULTS: Forty-seven per cent (range across
      countries [RAC] 2-77%) of sites had written TB IC plans; 60% (RAC 5-93%)
      practiced triage; of those with access to microscopy, 83% (RAC 59-91%) performed
      sputum collection outdoors and 13% (RAC 0-36%) in ventilated indoor rooms; 16%
      (RAC 1-87%) had particulate respirators available. Sites providing anti
      tuberculosis treatment were more likely to have written IC plans (54% vs. 12%, P
      < 0.0001) and particulate respirators (18% vs. 8%, P = 0.0126), and to perform TB
      triage (65% vs. 40%, P = 0.0001) than those without anti-tuberculosis treatment
      services. CONCLUSIONS: To protect HIV-infected patients and health care workers,
      there is an urgent need to scale up IC practices at HIV care and treatment sites,
      particularly at sites without anti-tuberculosis treatment services.

PMID- 23131258
TI  - Adult tuberculosis in Israel and migration: trends and challenges between 1999
      and 2010.
AB  - BACKGROUND: Israel absorbs many migrants from countries with a high prevalence of
      tuberculosis (TB). OBJECTIVES: To describe the epidemiology of TB among adults in
      Israel between 1999 and 2010 and identify populations with a high TB burden.
      DESIGN: Data were retrieved from the National Tuberculosis Registry and the
      Israeli Bureau of Statistics. RESULTS: A total of 4652 adult TB patients were
      notified during the study period, with rates decreasing annually from 7.5 per
      100,000 population in 1999 to 4.3 in 2010. Most (n = 3745, 80.5%) had pulmonary
      TB, the average female:male ratio was 1:1.4, and 227 (5.1%) were infected with
      the human immunodeficiency virus. Of all TB patients, 4079 (87.6%) were born
      outside Israel; of these, 3338 were citizens and 741 non-citizen migrant workers
      (MWs). The average annual rates of TB among Israeli-born citizens, foreign-born
      citizens and MWs were respectively 0.86, 11.9 and 27/100,000. The ratio of MWs to
      foreign-born citizens fell from 1:11.7 in 1999 to 1:1.5 in 2010. TB was diagnosed
      13.9 +/- 7.5 years following entry to Israel, mostly during the first year. Of
      3551 isolates, 222 (4.5%) were multidrug-resistant; most (95.6%) were from
      foreign-born patients. The average treatment success rate for smear-positive
      pulmonary TB was 84.3%. CONCLUSION: TB rates have decreased, while the proportion
      of foreign-born subjects, particularly MWs, has increased. Adherence to
      preventive treatment can prevent TB in these cases.

PMID- 23131259
TI  - Epidemiological impact of mass tuberculosis screening: a 2-year follow-up after a
      national prevalence survey.
AB  - OBJECTIVE: To assess the epidemiological impact of mass tuberculosis (TB)
      screening in the community and the prognosis of bacteriologically negative
      individuals with abnormal findings on chest radiography (CXR). METHODS: A follow
      up study consisting of two parts--a register match of notified TB cases with
      22,160 participants in a national TB prevalence survey, and a repeat medical
      examination for the subjects of a prevalence survey with abnormal findings on CXR
      -was conducted 2 years after the prevalence survey in Cambodia. RESULTS: Thirty
      four cases with new smear-positive TB were detected by register match, giving a
      standardised notification ratio of 0.38 (95%CI 0.27-0.52). An additional seven
      new smear-positive TB cases and 93 new smear-negative, culture-positive TB cases
      were detected by medical examination. The incidence rates of bacteriologically
      positive TB were 8.5% per year (95%CI 6.3-11.2) in cases with a CXR suggestive of
      active TB and 2.9% per year (95%CI 2.2-3.7) in those with a CXR with other
      abnormalities. CONCLUSIONS: Detection and treatment of smear-negative, culture
      positive TB cases as well as smear-positive TB cases was associated with a rapid
      reduction in subsequent incidence of new smear-positive TB. Sputum culture
      negative individuals with abnormal CXR findings are at a high risk of disease
      progression, and require follow-up and potentially preventive treatment.

PMID- 23131260
TI  - Suspected tuberculosis case detection and referral in private pharmacies in Viet
      Nam.
AB  - SETTINGS: Private pharmacies in Hanoi, Viet Nam. OBJECTIVES: To explore the
      response of health care providers (HCPs) in private pharmacies to suspected
      tuberculosis (TB) patients. METHODS: A simulated patient method combined with an
      interview in 128 randomly selected private pharmacies  and 10 private pharmacies
      near TB hospitals. RESULTS: In the simulated patient method and interview,
      respectively 59 (46%) and 70 (55%) of HCPs referred the TB suspect to general
      health care. Only 11 (9%) referred the simulated patient to a TB care facility.
      Fifty-two (42%) of the HCPs  identified suspected TB from a fictitious case
      described on paper; 34 (27%) were aware that free treatment was provided under
      the National Tuberculosis Programme (NTP). Knowledge about free NTP treatment
      predicted a higher rate of direct referrals to TB facilities (OR 5.80, 95%CI 1.88
      19.62)  and greater ability to identify suspected TB from a fictitious case on
      paper (OR 5.14, 95%CI 2.36-11.73). Pharmacies with Good Pharmacy Practice (GPP)
      certification were less likely to refer simulated patients to TB facilities than
      non-GPP pharmacies (OR 0.10, 95%CI <=0.01-0.79). CONCLUSIONS: Nearly half of HCPs
      in private pharmacies do not refer TB suspects, possibly contributing to delays
      in diagnosis and treatment. Knowledge about free NTP treatment predicted better
      performance of HCPs.

PMID- 23131261
TI  - Detection delay of pulmonary tuberculosis patients among migrants in China: a
      cross-sectional study.
AB  - OBJECTIVES: 1) To explore the characteristics of patient and diagnostic delays
      among migrant tuberculosis (TB) patients in Shandong, China; and 2) to identify
      factors associated with patient and diagnostic delays, for the development and
      improvement of TB control strategy among migrants  in China. DESIGN: A cross
      sectional study was conducted in 12 counties of Shandong Province using a semi
      structured questionnaire. A total of 314 smear-positive pulmonary migrant TB
      patients registered with the county TB dispensary of the sampling sites from 1
      August 2007 to 31 July 2008  were selected. RESULTS: Among 314 migrant TB
      patients, the median patient delay was 10 days, and the median diagnostic delay
      was 8 days. A quarter of the participants had a patient delay of >22 days and a
      diagnostic delay of >16 days. Factors affecting detection delay included
      financial  conditions, health insurance status, working time, patient age,
      severity of initial symptoms, geographic access to TB-related care and the health
      facilities first visited. CONCLUSIONS: Interventions such as expansion of the
      free service package and education about TB diagnosis among community  health
      personnel are urgently required for early case detection among migrants.

PMID- 23131262
TI  - Tuberculosis in the workplace: developing partnerships with the garment
      industries in Bangladesh.
AB  - OBJECTIVES: To implement and evaluate a public-private partnership model
      involving garment factories to reduce the tuberculosis (TB) burden in this
      workforce. DESIGN: We used operational research to develop and evaluate a
      mechanism for effective and sustainable TB control in workplaces in three areas
      of Dhaka, Bangladesh. Strategies, protocols, guides and tools were developed with
      stakeholders. We assessed the impact of the project using quantitative and
      qualitative measures: changes in TB outcomes were calculated using standard
      indicators based on factory and DOTS centre records; changes in TB care-seeking
      behaviour were assessed using qualitative in-depth interviews with factory
      managers and medical personnel, and focus group discussions with factory workers,
      including TB patients. FINDINGS: The project brought positive changes in
      knowledge, attitudes and practices of managers, workers and health care providers
      on TB care and control. During 2008-2010, a total of 3372 workers from a
      workforce of 69,000 were referred for sputum microscopy and 598 were diagnosed
      with smear-positive TB, 145 of whom received care at their workplace. The overall
      treatment success rate was 100%. CONCLUSION: It is feasible to engage factories
      in TB control activities in Bangladesh, and thereby increase case notifications
      and improve treatment outcomes.

PMID- 23131263
TI  - An evaluation of 'Ribolola': a household tuberculosis contact tracing programme
      in North West Province, South Africa.
AB  - SETTING: Rural/peri-urban community, South Africa. OBJECTIVES: To examine the
      yield of tuberculosis (TB) cases, TB preventive therapy (TBPT) initiation and
      human immunodeficiency virus (HIV) diagnoses from household TB contact tracing.
      DESIGN: Retrospective programme analysis. METHODS: Households of index TB cases
      were visited and their contacts screened for TB and HIV. TB suspects provided
      sputum or were referred for assessment. Contacts aged <5 years were referred for
      assessment for TBPT initiation. RESULTS: There were 732 index TB cases (67.1% HIV
      positive). Among  3627 household contacts, 3573 (98.5%) had known outcomes, of
      which 183 (5.0%) were already on appropriate treatment. Among 3390 remaining
      contacts, 361 (10.6%) were aged <5 years, of whom 34 (9.4%) started anti
      tuberculosis treatment and 286 (79.2%) started TBPT. Among 3029 contacts aged 
      >=5 years, 93 (3.1%) started anti-tuberculosis treatment: 19 (20.4%) were smear
      positive and 71 (76.3%) were culture-positive. Among contacts aged >=14 years,
      794/2133 (37.2%) underwent HIV testing, of whom 208/794 (26.2%) tested positive.
      CONCLUSIONS: Household active case finding  in this high TB and HIV prevalence
      setting obtained high yields of TB, particularly in those aged <5 years, and
      facilitated assessment for TBPT. There was a good yield of new HIV diagnoses, and
      a gain in efficiency due to integration within one programme.

PMID- 23131264
TI  - Risk factors for excess mortality and death in adults with tuberculosis in
      Western Kenya.
AB  - OBJECTIVES: To evaluate excess mortality and risk factors for death during anti
      tuberculosis treatment in Western Kenya. METHODS: We abstracted surveillance data
      and compared mortality rates during anti-tuberculosis treatment with all-cause
      mortality from a health and demographic  surveillance population to obtain
      standardised mortality ratios (SMRs). Risk factors for excess mortality were
      obtained using a relative survival model, and for death during treatment using a
      proportional hazards regression model. RESULTS: The crude mortality rate during
      anti-tuberculosis  treatment was 18.0 (95%CI 16.8-19.2) per 100 person-years. The
      age and sex SMR was 8.8 (95%CI 8.2-9.4). Excess mortality was greater in human
      immunodeficiency virus (HIV) positive TB patients (excess hazard ratio [eHR] 2.1,
      95%CI 1.5-3.1), and lower in patients who were female  or started treatment in a
      later year. Mortality was high in patients with unknown HIV status (HR 2.9, 95%CI
      2.2-3.8) or, if HIV-positive, not on antiretroviral treatment (ART; HR 3.3, 95%CI
      2.5-4.5) or not known to be on ART (HR 2.8, 95%CI 2.1-3.7). The attributable
      fraction  of incomplete uptake of HIV testing and ART on mortality was 31% (95%CI
      15-45) compared to HIV-positive patients on ART. CONCLUSION: Increasing the
      uptake of HIV testing and ART would further reduce mortality during anti
      tuberculosis treatment by an estimated 31%.

PMID- 23131265
TI  - Tuberculosis mortality: death from a curable disease, Connecticut, 2007-2009.
AB  - SETTING: Health Department Tuberculosis (TB) Control program, Connecticut, United
      States OBJECTIVE: 1) To assess TB-relatedness of deaths and missed opportunities
      among Connecticut patients who died with TB, and 2) to identify factors
      associated with death. DESIGN: The study population  consisted of all persons
      diagnosed with TB and reported to the Connecticut TB Control Program during 2007
      2009. TB Control Program records, medical records, autopsy reports and death
      certificates of decedents were reviewed. A tool was used to categorize TB
      relatedness of deaths and identify  missed opportunities in diagnosis and medical
      treatment among TB-related deaths. Surveillance data regarding TB survivors were
      used for comparison to identify factors associated with death. RESULTS: During
      2007-2009, 20/300 (7%) persons with TB died; 14 (70%) decedents had at least  one
      medical comorbidity and 17 (85%) deaths were TB-related. Among patients who had a
      TB-related death, 16 (94%) had >=1 missed opportunity identified. Excess alcohol
      use (risk ratio [RR] 4.4, 95% confidence interval [CI] 1.8-11.0) and age > 64
      years (RR 5.7, 95%CI 2.5-13.1)  were associated with death. CONCLUSIONS: The
      majority of deaths among Connecticut TB patients were TB-related. Missed
      opportunities were common. Excess alcohol use and older age might indicate a need
      for monitoring to prevent death.

PMID- 23131266
TI  - Prolonged positivity of sputum smears with negative cultures during treatment for
      pulmonary tuberculosis.
AB  - SETTING: Acid-fast bacilli (AFB) microscopy of sputum smears is the most widely
      used tool for both diagnosing pulmonary tuberculosis (PTB) and monitoring
      treatment response. It is not uncommon for patients who show clinical improvement
      to have prolonged positivity of sputum smears (i.e.,  >=60 days after initiation
      of treatment) with corresponding negative cultures. OBJECTIVE: To assess
      treatment outcomes and characteristics associated with prolonged smear-positive,
      culture-negative status. DESIGN: A retrospective review was performed of all
      patients seen by the Cuyahoga  County TB Program in Cleveland from 2000 to 2009.
      There were 159 consecutive smear-positive, drug-susceptible PTB cases with
      sufficient analyzable bacteriologic, clinical and radiographic data for study.
      RESULTS: A smear-positive, culture-negative pattern was seen in 51 patients
      (32.1%)  >=2 months after initiation of treatment. Age >=46 years and extent of
      baseline chest X-ray abnormality were both significantly associated with a
      prolonged smear-positive, culture-negative pattern. No patients were culture
      positive for Mycobacterium tuberculosis after >=2 months.  There was no increased
      risk of death in the prolonged smear-positive, culture-negative group, and no
      confirmed relapses. CONCLUSION: In our population of patients, in the absence of
      clinical or radiographic evidence of deterioration, late smear positivity usually
      has no clinical significance  and requires no specific action.

PMID- 23131267
TI  - Use of bronchoalveolar lavage enzyme-linked immunospot for diagnosis of smear
      negative pulmonary tuberculosis.
AB  - OBJECTIVE: To compare the diagnostic validity of blood enzyme-linked immunospot
      assay (ELISpot), broncho-alveolar lavage (BAL) ELISpot and the tuberculin skin
      test (TST) in patients with pulmonary smear-negative tuberculosis (TB) in a
      country with high TB prevalence. DESIGN: In a  prospective, hospital-based study,
      107 patients with suspected TB were tested simultaneously using blood and BAL
      ELISpot and TST. RESULTS: Of 102 patients with active pulmonary TB, 36 (35.3%)
      were diagnosed with TB, while 66/102 (64.7%) had a non-TB diagnosis. The
      sensitivity and specificity  for ELISpot on mononuclear cells from BAL fluid was
      respectively 94.4% (95%CI 81.9-98.5) and 78.1% (95%CI 66.6-86.5). The specificity
      of BAL ELISpot was significantly higher than that of blood ELISpot (P = 0.011).
      Compared with blood ELISpot and TST, BAL ELISpot was not  significantly
      influenced by previous history of TB (OR 2.05, P > 0.05) or household contact
      with a patient with active TB (OR 2.41, P > 0.05). CONCLUSION: ELISpot on BAL
      appears to be a more rapid and sensitive supplementary test than on blood for the
      diagnosis of active  TB patients with a negative sputum smear in a developing
      country setting with high TB prevalence and access to bronchoscopy and ELISpot
      assay. However, the test's utility was limited by its moderate specificity.

PMID- 23131268
TI  - Nucleic acid amplification test and bronchoscopy improve the diagnostic accuracy
      of smear-negative tuberculosis.
AB  - OBJECTIVE: To determine whether the nucleic acid amplification (NAA) test on
      specimens collected by bronchoscopy improves the diagnostic accuracy of pulmonary
      tuberculosis (PTB) in sputum-negative patients. DESIGN: Bronchoscopy was
      performed among smear-negative PTB suspects to collect  respiratory specimens to
      assess the efficacy and accuracy of the Amplified Mycobacterium Tuberculosis
      Direct (AMTD) test in the diagnosis of PTB. RESULTS: In 105 PTB suspects, 80 were
      finally excluded, of whom two were false-AMTD-positive. PTB (n = 25) was
      diagnosed in 10  patients culture-positive for Mycobacterium Tuberculosis (7/105
      bronchial wash/bronchoalveolar lavage [BW/BAL] specimens, 6/315 expectorated
      sputum specimens [2 positive in 2 patients; 1 positive in 2 patients], and one
      with both), and in 15 patients with improvement after anti-tuberculosis 
      treatment. Among the 25 PTB patients, 20 were AMTD-positive, of whom four were
      culture-positive. Three AMTD-negative patients were culture-positive. The
      sensitivity and specificity of AMTD were respectively 80.0% and 97.5%. The
      diagnostic yield was higher in respiratory specimens obtained  at bronchoscopy
      and measured by AMTD than in conventional sputum or BW/BAL culture. CONCLUSION:
      NAA testing on specimens collected using bronchoscopy provides a highly efficient
      and reliable approach in the diagnosis of PTB in smear-negative PTB suspects.

PMID- 23131269
TI  - The role of anthropometric and other predictors for diabetes among urban
      Tanzanians with tuberculosis.
AB  - BACKGROUND: As diabetes impairs tuberculosis (TB) treatment outcomes, it is
      essential to identify diabetes among TB patients. While little is known about
      predictors of diabetes among healthy individuals in Africa, predictors among TB
      patients are almost non-existent. OBJECTIVE: To  assess potential predictors for
      diabetes among newly diagnosed pulmonary TB patients in Tanzania. METHODS: TB
      patients were tested for diabetes using an oral glucose tolerance test,
      demographic information was collected and anthropometric measurements taken. The
      association between diabetes  and possible predictors were examined using
      logistic regression analyses. RESULTS: Of 1205 TB patients, 16.4% (n = 197) had
      diabetes, 9.0% (n = 108) were aged >=55 years, 3.3% (n = 40) were overweight
      (body mass index [BMI] >= 25 kg/m(2)) and 12.7% (n  = 152) severely underweight
      (BMI < 16 kg/m(2)). Diabetes was most prevalent in the 45-55 year age group, and
      increasing weight, BMI and waist circumference were associated with diabetes.
      Severe underweight (BMI < 16 kg/m(2)) among male TB patients (sex-BMI 
      interaction, P = 0.02) was associated with diabetes (OR 2.52, P = 0.004).
      CONCLUSION: Diabetes is a common comorbidity among TB patients. Although diabetes
      was associated with obesity and was more prevalent among the middle-aged, the
      majority of TB patients with diabetes comorbidity  were young and lean. With
      diabetes as a major risk factor for TB, and with the lack of strong predictors
      for diabetes, universal diabetes screening should be implemented in the TB
      programme.

PMID- 23131270
TI  - Differentiation of tuberculosis from lymphomas in neck lymph nodes with
      multidetector-row computed tomography.
AB  - BACKGROUND: Tuberculosis (TB) of the cervical lymph nodes may mimic lymphoma.
      OBJECTIVE: To evaluate multidetector-row computed tomographic (MDCT) imaging
      criteria for differentiating between the two diseases. MATERIALS AND METHODS: We
      retrospectively reviewed the anatomical distribution  and CT enhancement patterns
      of the nodes in 81 patients, 27 (33%) with untreated TB and 54 (67%) with
      untreated lymphomas involving cervical lymph nodes. Of the patients with
      lymphomas, 19 (35%) had Hodgkin's disease and 35 (65%) had non-Hodgkin's
      lymphoma. RESULTS: TB predominantly involved  the upper cervical nodes. The
      supraclavicula fossa nodes on MDCT were involved more often in Hodgkin's disease
      (n = 15, 79%) and non-Hodgkin's lymphoma (n = 25, 71%) than in TB (n = 3, 11%).
      Tuberculous lymphadenopathy commonly showed peripheral enhancement, frequently 
      with a multilocular appearance. Peripheral enhancement was significantly more
      frequent in TB (n = 19, 70%) than in Hodgkin's disease (n = 1, 5%) and non
      Hodgkin's lymphoma (n = 1, 3%), but homogeneous enhancement was less common in
      the TB group. CONCLUSION: Our findings  indicate that a specific enhancement
      pattern of lymphadenopathy seen on MDCT was useful in differentiating between
      untreated TB and lymphomas of the cervical lymph nodes.

PMID- 23131271
TI  - Household income, sex and respiratory mortality in Sao Paulo, Brazil, 1996-2010.
AB  - SETTING: Respiratory mortality rates are declining in several countries,
      including Brazil; however, the effect of socio-economic indicators and sex is
      unclear. OBJECTIVE: To identify differences in mortality trends according to
      income and sex in the city of Sao Paulo, Brazil. DESIGN: We performed a time
      trend analysis of all respiratory diseases, including chronic obstructive
      pulmonary disease (COPD), lung cancer and tuberculosis, using Joinpoint
      regression comparing high, middle and low household income levels from 1996 to
      2010. RESULTS: The annual per cent change  (APC) and 95% confidence intervals
      (95%CIs) for death rates from all respiratory disease in men in high-income areas
      was -1.1 (95%CI -2.7 to 0.5) in 1996-2002 and -4.3 (95%CI -5.9 to -2.8) in 2003
      2009. In middle- and low-income areas, the decline  was respectively -1.5 (95%CI 
      2.2 to -0.7) and -1.4 (95%CI -1.9 to -0.8). For women, the APC declined in high
      income (-1.0, 95%CI -1.9 to -0.2) and low-income areas (0.8, 95%CI -1.3 to -0.2),
      but not in middle-income areas (-0.5,  95%CI -1.4 to 0.3) from 1996 to 2010.
      CONCLUSION: Death rates due to COPD and all respiratory disease declined more
      consistently in men from high-income areas. Mortality due to lung cancer
      decreased in men, but increased in women in middle- and low-income areas.

PMID- 23131272
TI  - 100 years of mortality due to chronic obstructive pulmonary disease in Australia:
      the role of tobacco consumption.
AB  - BACKGROUND: Global studies of the long-term association between tobacco
      consumption and chronic obstructive pulmonary disease (COPD) have relied upon
      descriptions of trends. OBJECTIVES: To statistically analyse the relationship of
      tobacco consumption with data on mortality due to  COPD over the past 100 years
      in Australia. METHODS: Tobacco consumption was reconstructed back to 1887. Log
      linear Poisson regression models were used to analyse cumulative cohort and
      lagged time-specific smoking data and its relationship with COPD mortality.
      RESULTS: Age-standardised  COPD mortality, although likely misclassified with
      other diseases, decreased for males and females from 1907 until the start of the
      Second World War in contrast to steadily rising tobacco consumption. Thereafter,
      COPD mortality rose sharply in line with trends in smoking, peaking in the early 
      1970s for males and over 20 years later for females, before falling again.
      Regression models revealed both cumulative and time-specific tobacco consumption
      to be strongly predictive of COPD mortality, with a time lag of 15 years for
      males and 20 years for females. CONCLUSIONS: Sharp falls  in COPD mortality
      before the Second World War were unrelated to tobacco consumption. Smoking was
      the primary driver of post-War trends, and the success of anti-smoking campaigns
      has sharply reduced COPD mortality levels.

PMID- 23131273
TI  - The added effect of thioridazine in the treatment of drug-resistant tuberculosis.

PMID- 23131275
TI  - A case of hyperacute hepatotoxicity in response to tuberculosis therapy.

PMID- 23131276
TI  - Mycobacterium intracellulare bacteraemia in a double lung transplant patient.

PMID- 23131277
TI  - Acute eosinophilic pneumonia presenting as life-threatening hypoxaemia
      necessitating extracorporeal membrane oxygenation.

PMID- 23131278
TI  - [Methods and results of smoking cessation in cancer smoker's].
AB  - Tobacco prevention is the most effective prevention of cancer. Daily smoking
      promotes tumor progression, increases the risk of second cancer and decreases
      survival. The diagnosis of smoking and support for cessation and preventing
      recurrence is an integral part of cancer treatment. Smoking increases side
      effects of chemotherapy and surgery and reduces the effectiveness of radiotherapy
      and chemotherapy. Smokers with cancer do not smoke by life-style choice but
      because they are highly addicted and are suffering from a chronic relapsing
      disease: tobacco dependence, which justifies intensive medical management. The
      oncologist himself may perform this support or coordinate with other physicians
      in charge of the patient or with a tobacco cessation clinic, but patients are
      often unable to stop alone, as evidenced by the continued to use tobacco despite
      a cancer diagnosis. Treatment will always include a therapeutic education,
      compartmental behavioral therapy and medication. The patches and oral nicotine
      replacement or varenicline are the two most effective treatments that can be
      prescribed to smokers suffering of cancer, without including those with any
      motivation to quit. Smoking reducing occurred in a few days or weeks on treatment
      will allow them to reconsider the judgment. The full stop is always the goal for
      the doctor, even if it is not the patient initial goal. After stopping, the
      patient is not cured but still a patient with tobacco dependence who does not
      smoke. The risk of relapse in the year being 50%. The cancer patient management
      will use every visit to the point tobacco dependence and prevent relapse, alone
      or with assistance of a specialist. There is a lack of data on smoking cessation
      in cancer patients, but no item calls for a three-month quit rate of 50% as
      observed in the general population after an optimal management of tobacco
      cessation.

PMID- 23131279
TI  - [The correlation analysis between glucose level and its variability and prognosis
      in traumatic patients].
AB  - OBJECTIVE: To investigate the effect of glucose level, variability on the
      prognosis of traumatic patients. METHODS: A retrospective study involving 300
      traumatic patients admitted to intensive care unit (ICU) was performed. The
      average glucose (GluAve), glucose standard deviation (GluSD) and glucose
      coefficient of variation (GluCV) during the first 72 hours were calculated.
      Patients were divided into survivor group (n=249) and non-survivor group (n=51)
      based on outcomes. The GluAve, GluSD and GluCV were compared between the two
      groups. Patients were allocated into five subgroups based on GluAve (3.9-5.5, 5.6
      6.6, 6.7-7.7, 7.8-9.9, >=10.0 mmol/L) as well as four subgroups on GluCV (<15%,
      15%-30%, 30%-50%, >50%). The mortality in hospital was compared among the
      different subgroups and the different GluCV in the same level of GluAve
      subgroups, respectively. Multifactor logistic regression was used to determine
      the risk factor of hospital death. RESULTS: The levels of GluAve, GIuSD, GluCV of
      non-survivor group were higher than those of survivor group [11.31+/-4.38 mmol/L
      vs. 8.50+/-3.40 mmol/L, 2.85+/-1.94 mmol/L vs. 1.87+/-1.67 mmol/L, (28.30+/
      23.08)% vs. (20.90+/-13.70)%, all P<0.05]. With the gradual increment of GluAve
      and GluCV level, the mortality was raised accordingly (chi (2)(1)=26.332,
      P=0.000; chi (2)(2)=65.522, P=0.000). In the subgroup of GluAve 7.8-9.9 mmol/L,
      the mortality was 9.09% (3/33) with GluCV <15% versus 46.15% (6/13) with GluCV
      >50% (P<0.01) respectively, and in the subgroup of GluAve >=10.0 mmol/L, the
      mortality corresponding rates were 21.05% (4/19) with GluCV < 15% and 61.54%
      (8/13) with GluCV > 50% (P<0.05). The multivariable logistic regression analysis
      demonstrated that GluAve and GluCV were risk factors of mortality[GluAve odds
      ratio (OR)=1.150, 95% confidence interval (95%CI) was 1.042 to 1.270, P=0.006;
      GluCV OR=1.022, 95%CI was 0.999 to 1.040, P=0.040], GluSD had no effect on
      mortality. CONCLUSIONS: The increase in GluAve and GluCV in traumatic patients
      are significantly correlated with mortality. Control the level and the
      variability of blood glucose might be an important aspect of the multiple trauma
      death reduction.

PMID- 23131280
TI  - [Clinical study of kidney injury molecule-1 in the treatment of sepsis patients].
AB  - OBJECTIVE: To investigate the relationship between kidney injury molecule-1 (KIM
      1) in urine and acute physiology and chronic health evaluation II (APACHEII)
      score, and the prognosis in the patients suffered from sepsis. METHODS: In the
      perspective study, 56 patients in intensive care unit (ICU) from March 2010 to
      September 2011 suffered from sepsis were enrolled and treated according to the
      early goal-directed therapy (EGDT). The patients were divided into two groups
      according to the perform in EGDT or not within 6 hours (groupI, group II).
      Monitoring included APACHEII score, KIM-1, blood urea nitrogen (BUN) and
      creatinine (Cr) at before resuscitation (T0), 6 hours after resuscitation (T6 h),
      and 1 day (T1 d), 2 days (T2 d), 3 days (T3 d), 4 days (T4 d) and 5 days (T5 d)
      after ICU admission. According to the 28-day prognosis, all the patients were
      divided into survival group or death group. RESULTS: The value of APACHEII score,
      urine KIM-1, BUN and Cr in groupI(n=30), decreased after fluid resuscitation and
      decreased to the lowest at T5 d. The value of APACHEII score, urine KIM-1, BUN
      and Cr in groupII(n=26), increased after failure of fluid resuscitation and
      increased to the highest at T5 d. The value of APACHEII score at T2 d and urine
      KIM-1 at T1 d in groupII were significantly higher than those in groupI (APACHEII
      score: 26.35+/-6.18 vs. 13.25+/-4.72, urine KIM-1: 4.721+/-1.432 MUg/L vs.
      0.909+/-0.325 MUg/L, both P<0.05). The mortality in groupI was significantly
      lower than that in group II [10.0% (3/30) vs. 73.1% (19/26), P<0.05]. The value
      of APACHEII score, urine KIM-1, BUN and Cr in survival group (n=34) decreased
      with the clinical condition improved and decreased to the lowest at T5 d, while
      the value of APACHEII score, urine KIM-1, BUN and Cr in death group (n=22)
      increased and increased to the highest at T5 d. The value of APACHEII score at T1
      d, and urine KIM-1 at T6 d in death group were significantly higher than those in
      survival group (APACHEII score:26.39+/-8.95 vs. 14.27+/-5.11, urine KIM-1:3.134+/
      1.117 MUg/L vs. 1.447+/-0.472 MUg/L, both P<0.05). CONCLUSIONS: KIM-1 in urine
      could be a good index for evaluation of sepsis, and it is helpful to understand
      the disease development by continuous surveillance. It is very important for the
      appraisal of prognosis, development and prognosis in sepsis, combined with
      APACHEII score.

PMID- 23131281
TI  - [Effects of PNU282987 on organ function and survival in dogs with lethal burn
      shock].
AB  - OBJECTIVE: To investigate the effects of PNU282987, a alpha7 nicotinic
      acetylcholine receptor agonist (alpha7nAChR), on organ function and survival rate
      in dogs with lethal burn shock. METHODS: Twelve adult male Beagle dogs were
      subjected to 50% total body surface area (TBSA) full-thickness flame injury, and
      then they were randomly divided into a burn group and a PNU282987 group (PNU
      group), each n=6. The dogs in PNU group received PNU282987 (0.38 mg/kg, venous
      pumping) and the dogs in burn group received equal amount of normal saline
      solution as the control group. The mean arterial pressure (MAP) and the plasma
      levels of tumor necrosis factor-alpha (TNF-alpha), alanine aminotransferase
      (ALT), MB isoenzyme of creatine kinase (CK-MB), creatinine (Cr), blood urea
      nitrogen (BUN) were continuously determined before and 0.5, 2, 4, 8, 12, 24 hours
      after burn. All the above measurements were performed with animals in conscious
      and cooperative state. At the end of 24-hours-period experiment, the survival
      rate was recorded. RESULTS: The MAP significantly decreased after burn compared
      with the baseline data before-injury. The level of MAP in PNU group were
      significantly higher than those of the burn group from 4 hours after burn, and it
      returned to 83.6% of baseline level at 24 hours. In contrast, those in the burn
      group progressively decreased with time till death. The plasma levels of TNF
      alpha in PNU group were significantly lower than those of burn group at each time
      points post injury. The ALT, Cr, BUN  and CK-MB of the burn group increased
      persistently, while those of the PNU group increased at first and decreased
      subsequently except for ALT increased persistently, and they were all
      significantly lower than those of the burn group till to the time point of 12
      hours (ALT:51.2+/-7.0 U/L vs. 104.8+/-7.4 U/L, Cr:42.7+/-5.4 MUmol/L vs. 88.5+/
      4.8 MUmol/L, BUN:4.9+/-1.2 mmol/L vs. 14.7+/-1.4 mmol/L, CK-MB:564.0+/-39.1 U/L
      vs. 734.0+/-35.9 U/L, all P<0.05). At the end of 24-hours-period experiment, the
      survival rate of the PNU group was 50% (3/6) and significantly higher than that
      of the burn group 0(0/6). CONCLUSIONS: The results indicated that PNU282987
      decrease the levels of inflammatory cytokine, improve the organ functions and
      increase 24-hour survival rate in dogs with lethal burn injury. And PNU282987 may
      have potential clinical application.

PMID- 23131282
TI  - [Characteristics of the confined space accident and its medical rescue strategy].
AB  - OBJECTIVE: To investigate the characteristics of the confined space accident and
      its medical rescue strategy. METHODS: Thirty-six patients with emergency rescue
      in the five confined space accident during June 2009 to July 2012 were
      retrospectively analyzed. RESULTS: Twenty-nine people were caught in four
      confined space accidents caused by building collapse and 7 people were caught in
      one confined space accident caused by a tower of babel blast furnace damage which
      caused severe gas and hydrogen sulfide poisoning. For the 36 wounded, the
      shortest rescue time was 1.5 hours and the longest was 10.5 hours. Fourteen
      people were killed (mortality rate 38.89%). Characteristics of the confined space
      accident: the wounded activity environment was very harsh, the wounded were
      restricted particularly, the wounded injuries were diverse, the psychological
      depression was very common. The confined space environment and the complexity of
      wounded disease determined its medical rescue specificity and were very different
      from the usual trauma emergency. CONCLUSIONS: Confined space accident caused very
      painful casualties. The key reason is that the relevant personnel failed to
      clearly recognize the potential risks in the confined space or nearby, making the
      confined space into another "quiet killer". This problem needs to be paid highly
      attention.

PMID- 23131283
TI  - [Plasma D-dimer changes and prognostic implication in severe acute pancreatitis].
AB  - OBJECTIVE: To study the role of plasma D-dimer in human severe acute pancreatitis
      (SAP) and its relationship with disease severity. METHODS: A prospective study
      was performed. From February 2010 to June 2011, plasma concentration of D-dimer
      and the results of other routine laboratory tests were measured in 32 SAP
      inpatients at admission immediately and 24, 48, 72 hours after admission. Ranson
      scores were also recorded. The relationship between plasma concentration of D
      dimer and the results of other routine laboratory tests, Ranson scores were
      analyzed, and so did the relationship between plasma concentration of D-dimer and
      severity of patient's condition. RESULTS: (1) There were no obvious changes for
      plasma concentration of D-dimer and the results of other routine laboratory index
      in 32 SAP inpatients at each time points after admission. (2) Plasma
      concentration of D-dimer of SAP was positively related to white blood count
      (WBC), creatinine (Cr), prothrombin time (PT) and activated partial
      thromboplastin time (APTT) and negatively related to hematocrit (Hct), albumin
      and calcium (P<0.05 or P<0.01). Plasma concentration of D-dimer of SAP at 48
      hours after admission had positive relationship with Ranson scores (r=0.729,
      P=0.001). (3) Plasma concentration of D-dimer of SAP inpatients in CT grade D, E
      stage were significantly higher than that in CT grade B, C stage (1.18+/-0.02
      mg/L, 1.23+/-0.01 mg/L vs. 0.90+/-0.02 mg/L, 0.93+/-0.01 mg/L, all P<0.05). (4)
      Plasma concentration of D-dimer of SAP in inpatients with multiple organ failure
      (MOF) at 24 hours and 48 hours were significantly higher than that in inpatients
      without MOF (24 hours: 1.26+/-0.02 mg/L vs. 0.93+/-0.02 mg/L, 48 hours:1.25+/
      0.02 mg/L vs. 0.93+/-0.02 mg/L, both P<0.05). CONCLUSION: Plasma concentration of
      the D-dimer is significantly increased in SAP patients, and is related to the
      severity. The first plasma concentration of D-dimer of SAP after admission can
      well reflect severity of patient's condition.

PMID- 23131284
TI  - [The relationship between the level of N-terminal pro-B-type natriuretic peptide
      and prognosis in patients with sepsis].
AB  - OBJECTIVE: To detect the relationship between the level of N-terminal pro-B-type
      natriuretic peptide (NT-proBNP) and prognosis in patients with sepsis. METHODS: A
      prospective controlled study was conducted. Sixty cases, including 39 sepsis and
      21 severe sepsis, were enrolled from May 2010 to October 2011 in intensive care
      unit (ICU) of Second Hospital of Tianjin Medical University. The serum level of
      NT-proBNP was determined and acute physiology and chronic health evaluation II
      (APACHEII) score was calculated on the 1st and 3rd day. The receiver operator
      characteristic curve (ROC curve) was draw. According to the 28-day prognosis, all
      patients were divided into the survival group (n=42) or the death group (n=18).
      At the same time 30 healthy people were enrolled as control group. RESULTS: The
      level of NT-proBNP in the sepsis patients on the 1st and 3rd day were
      significantly higher than those of healthy controls (65.77+/-34.78 ng/L, 74.23+/
      42.12 ng/L vs. 48.36+/-35.53 ng/L, P<0.05 and P<0.01). The level on 1st day of
      the severe sepsis group was higher than sepsis group (71.69+/-32.86 ng/L vs.
      50.11+/-36. 98 ng/L, P<0.05), but there was no statistically significance on the
      3rd day. The level of NT-proBNP in death group was increased gradually and
      significantly higher than that of survival group on the 3rd days (99.20+/-44.34
      ng/L vs. 66.79+/-39.28 ng/L, P<0.05), but no difference was found on the 1st day.
      The APACHEII score of severe sepsis group were much higher than those of sepsis
      group on the 1st and 3rd day (1st day:23.92+/-7.57 vs. 14.87+/-6.50, 3rd
      day:19.28+/-8.80 vs. 10.43+/-7.27, both P<0.01). The APACHEII score of death
      group were also much higher than those of survival group on the 1st and 3rd day
      (1st day:26.71+/-6.72 vs. 18.83+/-7.84, 3rd day:31.11+/-5.06 vs. 13.80+/-7.27,
      both P<0.01). The cut point for the evaluation of sepsis prognosis were NT
      proBNP>=63.5 ng/L and APACHEII score>=20, which sensitivity were 65.4% and 88.5%,
      and specificity were 62.5% and 69.4% respectively. CONCLUSION: Serum NT-proBNP
      levels elevation imply the poor prognosis in patients with sepsis.

PMID- 23131285
TI  - [The study of continuous blood purification in severe asthma].
AB  - OBJECTIVE: To explore the mechanism that continuous blood purification (CBP)
      improve the lung mechanical ventilation parameters, cytokine levels and blood gas
      analysis results in severe asthma patients, and compare the differences in those
      parameters between bicarbonate and lactate displacement liquid. METHODS:
      According to the random number table, 26 severe asthma patients were allocated
      into control group (n=10), bicarbonate group (n=8) and lactate group (n=8).
      Twenty-four hours treatment with mechanical ventilation (control group),
      mechanical ventilation + CBP (bicarbonate group) or mechanical ventilation + CBP
      (lactate group) were conducted respectively. Lung mechanical ventilation
      parameters, serum cytokine level and blood gas analysis results, arterial blood
      lactate, and electrolytes level were compared among groups. RESULTS: After 24
      hour CBP, the lung mechanical ventilation parameters were improved, cytokine
      levels were decreased, and pH value and partial pressure of oxygen were improved
      in bicarbonate group and lactate group. The two kinds of displacement liquid had
      no influence in arterial partial pressure of oxygen (PaO(2)), arterial blood
      lactate, and serum electrolytes level. The pH value in lactate group was higher
      than that in bicarbonate group (7.39+/-0.05 vs. 7.30+/-0.01, P<0.01). The
      arterial partial pressure of carbon dioxide (PaCO(2)) was lower in lactate group
      than that in bicarbonate group (57.14+/-5.04 mm Hg vs. 89.00+/-3.66 mm Hg,
      P<0.01). CONCLUSIONS: Combine CBP might improve the lung mechanical ventilation
      parameter, cytokine level and blood gas analysis more quickly in severe asthma
      treatment. The lactate displacement liquid improves the retention of carbon
      dioxide more.

PMID- 23131286
TI  - [Clinical study of value of transcranial Doppler ultrasonography in diagnosing
      brain death in severe craniocerebral injury].
AB  - OBJECTIVE: To assess the clinical value of transcranial Doppler(TCD)
      ultrasonography in diagnosing brain death in patients with severe craniocerebral
      injury. METHODS: Forty patients of severe craniocerebral injury defined by a
      scene Glasgow coma scale(GCS)<=8, admitted to Department of Neurosurgery of First
      Central Clinical Hospital of Tianjin Medical University, were divided into two
      groups based upon the prognosis: the death group(n=15) and the survival group
      (n=25). All patients were examined dynamically by TCD, and the occurrence of
      retrograde diastolic flow (RDF) and mean velocity (Vm) of middle cerebral
      arteries (MCA) were measured as well as the pulse index (PI). RESULTS: In the
      survival group, 3 showed partial RDF which was found within 24 hours after
      injury, and the duration was short lasting for no more than 12 hours, and the RDF
      wave disappeared very quickly after treatment of drug or operation. These
      patients were in persistent vegetative state with Glasgow outcome score (GOS) 2,
      having been followed up for 6 months. In the death group, 12 showed fully RDF, 2
      showed very small systolic spike. The characteristic change of 14 patients'
      cerebral hemodynamics took place 6-40 hours before clinical brain death. Compared
      with survival group, Vm of MCA was significantly decreased (20.07+/-13.97 cm/s
      vs. 56.72+/-16.87 cm/s), the value of PI was significantly increased (3.95+/-3.51
      vs. 1.25+/-1.06), and the occurrence of RDF was also elevated (93.3% vs. 12.0%)
      in the death group, the differences were statistically significant (P<0.05 or
      P<0.01). CONCLUSION: TCD with the advantages of easy and bedside operation,
      noninvasiveness, no disturbance from sedatives and repeatability in cerebral
      hemodynamic examination is of great clinic practical value in early diagnosing
      brain death in patients with severe cranial injury.

PMID- 23131287
TI  - [Clinical observation of the role of Chenxia Sijunzi decoction in promoting the
      recovery of gastrointestinal function in critically ill patients].
AB  - OBJECTIVE: To observe the clinical effects of Chenxia Sijunzi decoction on
      promoting gastrointestinal function recovery in severe patients. METHODS: A
      prospective randomized controlled study was conducted. Eighty severe patients
      feeding with enteral nutrition from September 2011 to March 2012 were divided
      into three groups according to the method of random number table. The traditional
      Chinese medicine group and western medicine group were consisted of 35 cases
      respectively, and 10 cases were control group. Control group was routine
      symptomatically treated without any medicines for promoting gastrointestinal
      power function, helping the lower extremities to move and enhancing the turn
      over, letting the gastrointestinal function recover by its self. Chinese medicine
      group was tube fed with Chenxia Sijunzi decoction on the basis of control group,
      western medicine group was tube fed with the multienzyme tablets and mosapride
      dispersible tablets on the basis of control group. Then the differences in bowel
      sound recovery time and the time for passage of gas by anus and the bowel
      movement time and length of stay in hospitals within three groups were observed.
      RESULTS: The time of bowel sound recovery (41.02+/-7.52 hours, 44.02+/-6.23
      hours), gas passage time by anus (49.90+/-6.95 hours, 51.32+/-5.12 hours) and the
      bowel movement time (58.22+/-6.71 hours, 60.91+/-3.72 hours) in both traditional
      Chinese medicine and the western medicine group were significantly reduced
      compared with the control group (54.62+/-5.51 hours, 64.68+/-9.47 hours, 78.20+/
      7.11 hours, all P<0.01), and the days in hospital (5.1+/-1.7 days, 5.0+/-1.5
      days) were shortened significantly compared with the control group (8.9+/-1.4
      days, both P<0.01). However, results did not demonstrate any significant
      differences in each testing index between traditional Chinese medicine and
      western medicine group (all P>0.05). CONCLUSION: Chenxia Sijunzi decoction can
      promote severe patient's gastrointestinal function recovery and reduce
      hospitalization days.

PMID- 23131288
TI  - [Effect of ulinastatin in traumatic brain injury with multiple injuries].
AB  - OBJECTIVE: To investigate the effect of ulinastatin (UTI) in traumatic brain
      injury (TBI) with multiple injuries. METHODS: A prospective analysis of TBI
      patients with multiple injuries was performed. Sixty cases of cranial trauma with
      multiple injuries patients were randomly divided into two groups. There were 28
      cases in control group while 32 cases in treatment group. Control group underwent
      conventional treatment while intravenous infusion of UTI was performed in
      treatment group. The dose of UTI was 200 kU every 8 hours. Patients' intracranial
      cerebral pressure (ICP) were monitored at admission and 10 days after treatment.
      At the same time levels of white blood cell (WBC), C-reactive protein (CRP),
      procalcitonin (PCT), alanine aminotransferase (ALT), aspartate amino transfer
      enzymes (AST), creatinine (Cr), blood urea nitrogen (BUN), tumor necrosis factor
      alpha (TNF-alpha), interleukin (IL-2, IL-6) were detected. RESULTS: ICP was down
      trend after treatment in UTI group, but there was no statistical difference
      compared with the control group. Hepatic and renal function and inflammation
      factor levels were significantly decreased in both groups. WBC, CRP, PCT, ALT,
      AST, Cr, BUN, TNF-alpha, IL-2, IL-6 were significantly lower in UTI group than
      those in control group (WBC:12.3+/-4.5*10(9)/L vs. 15.9+/-6.3*10(9)/L,
      CRP:46.12+/-11.47 mg/L vs. 64.24+/-18.31 mg/L, PCT:4.51+/-1.27 MUg/L vs. 10.51+/
      4.27 MUg/L, ALT:47.26+/-8.23 U/L vs. 60.94+/-8.39 U/L, AST:42.67+/-7.63 U/L vs.
      68.51+/-10.17 U/L, Cr:79.62+/-15.36 MUmol/L vs. 102.36+/-16.82 MUmol/L,
      BUN:6.35+/-2.36 mmol/L vs. 8.39+/-1.67 mmol/L, TNF-alpha:93.6+/-31.5 MUg/L vs.
      195.8+/-23.9 MUg/L, IL-2:12.3+/-4.5 MUg/L vs. 15.9+/-6.3 MUg/L, IL-6:52.36+/
      12.46 MUg/L vs. 69.34+/-26.13 MUg/L, all P<0.05). The incidence of systemic
      inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome
      (MODS) in UTI group were significantly lower than those in control group (21.88%
      vs. 46.43%, 9.38% vs. 28.57%, both P<0.05). CONCLUSION: Application of UTI
      treatment in TBI with multiple trauma patients can potentially protect the brain,
      liver and other organ function, thus significantly reduce incidence rate of SIRS
      and MODS by reducing the release of inflammatory mediators and systemic reaction
      to the trauma invasion.

PMID- 23131289
TI  - [Analysis on the clinical pulmonary infection score on the detection of multidrug
      resistance organisms in lower respiratory tract in ventilated patients in
      intensive care unit].
AB  - OBJECTIVE: To investigate the characteristics of multidrug resistance (MDR)
      organisms from the lower respiratory tract in ventilated patients, and the
      constitution, detection time and mortality of the intensive care unit (ICU)
      patients with different clinical pulmonary infection scores (CPIS). METHODS: A
      retrospective study was conducted. The clinical data of 72 cases with lower
      respiratory tract MDR on ventilation more than 48 hours were collected from April
      2010 to December 2011. CPIS were calculated at the same time. Thirty-three
      patients with CPIS>6 were diagnosed as ventilation associated pneumonia (VAP),
      while 39 having CPIS <=6 (non-VAP). The characteristics of MDR, the detection
      time and mortality of the patients were compared between the two groups. RESULTS:
      The first five MDR were Baumannii [49.5%(34/74)], Klebsiella pneumoniae
      [24.3%(18/74)], Escherichia coli [20.3%(15/74)], Pseudomonas aeruginosa
      [5.4%(4/74)] and Methicillin-resistant Staphylococcus aureus [MRSA, 4.1%(3/74)]
      in VAP group, while the first five were Escherichia coli [40.2%(37/92)],
      Pseudomonas aeruginosa [33.7%(31/92)], Klebsiella pneumoniae [13.1%(12/92)],
      Baumannii [8.7%(8/92)] and MRSA [4.3%(4/92)] in non-VAP group. There was no
      significant difference in average detection time between VAP group and non-VAP
      group (10.7+/-1.5 days vs. 9.4+/-1.8 days, P>0.05). The mortality rate in VAP
      group was significantly higher than that in non-VAP group (39.4% vs. 23.1%,
      P<0.05). CONCLUSIONS: Different MDR may be detected in lower respiratory tracts
      no matter the ventilated patients having VAP or not, which influence the patients
      prognosis and should be monitored intensively. Antibiotics should be empirically
      prescribed and adjusted dynamically.

PMID- 23131290
TI  - [Effect of dexmedetomidine assisted with brachial plexus block on stress in acute
      trauma patients].

PMID- 23131291
TI  - [Neonatal rat cerebral cortical neurons culture method].

PMID- 23131292
TI  - [Hemodynamic effects of midazolam and fentanyl combination in multiple trauma
      patients].

PMID- 23131293
TI  - [Treatment of acute chlorine poisoning with chemical-induced lung injury using
      high-dose dexamethasone combined with anisodamine: a report of 526 patients].

PMID- 23131294
TI  - [The research progress on prevention and treatment of pulmonary injury after
      liver transplantation in chronic severe hepatitis].

PMID- 23131295
TI  - [The research progress on acute lung injury following liver transplantation].

PMID- 23131296
TI  - [Advance in the research of the relationship between novel gaseous signal
      molecule-hydrogen sulfide and hepatic fibrosis].

PMID- 23131297
TI  - The role of multiple partners in a digestive mutualism with a protocarnivorous
      plant.
AB  - BACKGROUND AND AIMS: The protocarnivorous plant Paepalanthus bromelioides
      (Eriocaulaceae) is similar to bromeliads in that this plant has a rosette-like
      structure that allows rainwater to accumulate in leaf axils (i.e. phytotelmata).
      Although the rosettes of P. bromelioides are commonly inhabited by predators
      (e.g. spiders), their roots are wrapped by a cylindrical termite mound that grows
      beneath the rosette. In this study it is predicted that these plants can derive
      nutrients from recycling processes carried out by termites and from predation
      events that take place inside the rosette. It is also predicted that bacteria
      living in phytotelmata can accelerate nutrient cycling derived from predators.
      METHODS: The predictions were tested by surveying plants and animals, and also by
      performing field experiments in rocky fields from Serra do Cipo, Brazil, using
      natural abundance and enriched isotopes of (15)N. Laboratory bioassays were also
      conducted to test proteolytic activities of bacteria from P. bromelioides
      rosettes. KEY RESULTS: Analyses of (15)N in natural nitrogen abundances showed
      that the isotopic signature of P. bromelioides is similar to that of carnivorous
      plants and higher than that of non-carnivorous plants in the study area. Linear
      mixing models showed that predatory activities on the rosettes (i.e. spider
      faeces and prey carcass) resulted in overall nitrogen contributions of 26.5 % (a
      top-down flux). Although nitrogen flux was not detected from termites to plants
      via decomposition of labelled cardboard, the data on (15)N in natural nitrogen
      abundance indicated that 67 % of nitrogen from P. bromelioides is derived from
      termites (a bottom-up flux). Bacteria did not affect nutrient cycling or nitrogen
      uptake from prey carcasses and spider faeces. CONCLUSIONS: The results suggest
      that P. bromelioides derive nitrogen from associated predators and termites,
      despite differences in nitrogen cycling velocities, which seem to have been
      higher in nitrogen derived from predators (leaves) than from termites (roots).
      This is the first study that demonstrates partitioning effects from multiple
      partners in a digestion-based mutualism. Despite most of the nitrogen being
      absorbed through their roots (via termites), P. bromelioides has all the
      attributes necessary to be considered as a carnivorous plant in the context of
      digestive mutualism.

PMID- 23131298
TI  - Sterile flowers increase pollinator attraction and promote female success in the
      Mediterranean herb Leopoldia comosa.
AB  - BACKGROUND AND AIMS: Large floral displays have opposing consequences for animal
      pollinated angiosperms: they attract more pollinators but also enable elevated
      among-flower self-pollination (geitonogamy). The presence of sterile flowers as
      pollinator signals may enhance attraction while allowing displays of fewer open
      fertile flowers, limiting geitonogamy. The simultaneous contributions of fertile
      and non-fertile display components to pollinator attraction and reproductive
      output remain undetermined. METHODS: The simultaneous effects of the presence of
      sterile flowers and fertile-flower display size in two populations of Leopoldia
      comosa were experimentally assessed. Pollinator behaviour, pollen removal and
      deposition, and fruit and seed production were compared between intact plants and
      plants with sterile flowers removed. KEY RESULTS: The presence of sterile flowers
      almost tripled pollinator attraction, supplementing the positive effect of the
      number of fertile flowers on the number of bees approaching inflorescences.
      Although attracted bees visited more flowers on larger inflorescences, the number
      visited did not additionally depend on the presence of sterile flowers. The
      presence of sterile flowers improved all aspects of plant performance, the
      magnitude of plant benefit being context dependent. During weather favourable to
      pollinators, the presence of sterile flowers increased pollen deposition on
      stigmas of young flowers, but this difference was not evident in older flowers,
      probably because of autonomous self-pollination in poorly visited flowers. Total
      pollen receipt per stigma decreased with increasing fertile display size. In the
      population with more pollinators, the presence of sterile flowers increased fruit
      number but not seed set or mass, whereas in the other population sterile flowers
      enhanced seeds per fruit, but not fruit production. These contrasts are
      consistent with dissimilar cross-pollination and autonomous self-pollination,
      coupled with the strong predispersal inbreeding depression exhibited by L. comosa
      populations. CONCLUSIONS: Sterile flowers enrich pollination quality by promoting
      pollen export and import, while limiting the mating costs of geitonogamy
      associated with large fertile displays.

PMID- 23131299
TI  - Using the biomass-ratio and idiosyncratic hypotheses to predict mixed-species
      litter decomposition.
AB  - BACKGROUND AND AIMS: A test is made of the acceptability of the biomass-ratio
      hypothesis (BMRH), operationalized as community-weighted means (CWMs), and of a
      new hypothesis (idiosyncratic annulment), for predicting the decomposition of
      multispecies litter mixtures. Specifically, (1) does the BMRH based on
      monoculture decomposition rates introduce systematic over- or underestimation of
      rates in mixtures? and (2) does the degree of variability of these rates decrease
      with increasing species richness (SR) beyond that expected from purely
      mathematical causes? METHODS: Decomposition rates (mg g(-1) d(-1)) of litter from
      six tree species in microcosms were measured under controlled conditions during
      18 weeks of incubation, alone and in all possible combinations of two, three,
      five and six species. Observed mixture decomposition rates were compared with
      those predicted by the BMRH using CWMs calculated from the monoculture rates, and
      the variability of the differences were compared with the SR of the mixture. KEY
      RESULTS: Both positive and negative deviations from expectation occurred at all
      levels of SR. The average differences between observed rates of mixtures and
      those predicted were approximately zero. Although variability in the prediction
      errors was independent of the SR, this variability between different mixtures
      having the same number of species decreased with increasing SR such that mixtures
      with the most species converged on the predicted values. This decrease in
      variance was not due to idiosyncratic annulment of higher order interactions
      between species. CONCLUSIONS: The BMRH described the average response of litter
      mixtures. The decrease in variance and the convergence to the predicted values
      based on CWMs was not due to the 'idiosyncratic annulment' of species
      interactions but was a mathematical consequence of CWMs being sums of random
      variables. Since convergence occurs with increasing SR and since SR increases
      with increasing spatial scale, the spatial scale will be a determinant in the
      prediction of ecosystem processes, such as litter decomposition rates.

PMID- 23131300
TI  - Regulation of soybean seed germination through ethylene production in response to
      reactive oxygen species.
AB  - BACKGROUND AND AIMS: Despite their toxicity, reactive oxygen species (ROS) play
      important roles in plant cell signalling pathways, such as mediating responses to
      stress or infection and in programmed cell death, at lower levels. Although
      studies have indicated that hydrogen peroxide (H(2)O(2)) promotes seed
      germination of several plants such as Arabidopsis, barley, wheat, rice and
      sunflower, the role of H(2)O(2) in soybean seed germination is not well known.
      The aim of this study therefore was to investigate the relationships between ROS,
      plant hormones and soybean seed germination. METHODS: An examination was made of
      soybean seed germination, the expression of genes related to ethylene
      biosynthesis, endogenous ethylene contents, and the number and area of cells in
      the root tip, using N-acetylcysteine, an antioxidant, to counteract the effect of
      ROS. KEY RESULTS: H(2)O(2) promoted germination, which N-acetylcysteine
      suppressed, suggesting that ROS are involved in the regulation of soybean
      germination. H(2)O(2) was produced in the embryonic axis after imbibition. N
      Acetylcysteine suppressed the expression of genes related to ethylene
      biosynthesis and the production of endogenous ethylene. Interestingly, ethephon,
      which is converted to ethylene, and H(2)O(2) reversed the suppression of seed
      germination by N-acetylcysteine. Furthermore, morphological analysis revealed
      that N-acetylcysteine suppressed cell elongation at the root tip, and this
      suppression was also reversed by ethephon or H(2)O(2) treatments, as was the case
      in germination. CONCLUSIONS: In soybean seeds, ROS produced in the embryonic axis
      after imbibition induce the production of endogenous ethylene, which promotes
      cell elongation in the root tip. This appears to be how ROS regulate soybean seed
      germination.

PMID- 23131302
TI  - [The mouse as preclinical models of lung cancer].
AB  - The high incidence and poor prognosis of lung cancer represent a major health
      problem. Currently, about 20% of lung cancer patients can benefit from targeted
      therapy after identification of EGFR, ALK or HER2 somatic mutations or
      rearrangements. Other mutations, such as KRas oncogenic mutation, are still
      orphans of validated targeted therapy. In this review, we describe the different
      mouse models of lung carcinoma. We then illustrate the interests of such models
      for the identification and validation of new therapeutic targets, for the study
      of secondary resistance and for their use as preclinical models and for new
      therapeutic strategy tests.

PMID- 23131301
TI  - A study of the relationships of cultivated peanut (Arachis hypogaea) and its most
      closely related wild species using intron sequences and microsatellite markers.
AB  - BACKGROUND AND AIMS: The genus Arachis contains 80 described species. Section
      Arachis is of particular interest because it includes cultivated peanut, an
      allotetraploid, and closely related wild species, most of which are diploids.
      This study aimed to analyse the genetic relationships of multiple accessions of
      section Arachis species using two complementary methods. Microsatellites allowed
      the analysis of inter- and intraspecific variability. Intron sequences from
      single-copy genes allowed phylogenetic analysis including the separation of the
      allotetraploid genome components. METHODS: Intron sequences and microsatellite
      markers were used to reconstruct phylogenetic relationships in section Arachis
      through maximum parsimony and genetic distance analyses. KEY RESULTS: Although
      high intraspecific variability was evident, there was good support for most
      species. However, some problems were revealed, notably a probable polyphyletic
      origin for A. kuhlmannii. The validity of the genome groups was well supported.
      The F, K and D genomes grouped close to the A genome group. The 2n = 18 species
      grouped closer to the B genome group. The phylogenetic tree based on the intron
      data strongly indicated that A. duranensis and A. ipaensis are the ancestors of
      A. hypogaea and A. monticola. Intron nucleotide substitutions allowed the ages of
      divergences of the main genome groups to be estimated at a relatively recent 2.3
      2.9 million years ago. This age and the number of species described indicate a
      much higher speciation rate for section Arachis than for legumes in general.
      CONCLUSIONS: The analyses revealed relationships between the species and genome
      groups and showed a generally high level of intraspecific genetic diversity. The
      improved knowledge of species relationships should facilitate the utilization of
      wild species for peanut improvement. The estimates of speciation rates in section
      Arachis are high, but not unprecedented. We suggest these high rates may be
      linked to the peculiar reproductive biology of Arachis.

PMID- 23131303
TI  - Etomidate puts patients at risk of adrenal crisis.

PMID- 23131304
TI  - Pathophysiology of sudden cardiac death as demonstrated by molecular pathology of
      natriuretic peptides in the myocardium.
AB  - Various heart diseases present with sudden death; however, it is difficult to
      interpret the severity of or difference in respective preexisting and terminal
      cardiac dysfunction based on conventional morphology. The present study
      investigated the cardiac pathophysiology employing quantitative mRNA measurement
      of atrial and brain natriuretic peptides (ANP and BNP) in the myocardium as
      markers of cardiac strain, using autopsy materials consisting of acute ischemic
      heart disease (AIHD, n=40) with/without the pathology of apparent myocardial
      necrosis (n=19/21), recurrent myocardial infarction (RMI, n=19), chronic
      congestive heart disease (CHD, n=11) and right ventricular cardiomyopathy (RVC,
      n=5), as well as hemopericardium (HP, n=11) due to myocardial infarction (n=5)
      and aortic rupture (n=6), and acute pulmonary thromboembolism (PTE, n=5). Cardiac
      death groups showed higher ANP and/or BNP mRNA expressions in the left ventricle
      than acute fatal bleeding (sharp instrumental injury; n=15) and/or mechanical
      asphyxiation (strangulation; n=10). AIHD and RMI cases had similar ANP and BNP
      mRNA expressions in bilateral ventricular walls, but their bilateral atrial
      levels were lower in RMI. RVC showed higher mRNA expressions of posterior left
      ventricular BNP, and right ventricular and bilateral atrial ANP and BNP. HP cases
      had lower BNP mRNA expression in the right ventricular wall, but PTE showed lower
      ANP and BNP mRNA expressions in the left ventricular wall; however, these mRNA
      expressions at other sites were similar to those of AIHD. CHD presented findings
      similar to those of AIHD, but the pericardial BNP level was significantly
      increased. These observations indicate characteristic molecular biological
      responses of myocardial natriuretic peptides in individual heart diseases and
      suggest the possible application of molecular pathology to demonstrate cardiac
      dysfunction even after death.

PMID- 23131305
TI  - The incidence of alcohol and other drugs in drivers killed in New Zealand road
      crashes 2004-2009.
AB  - Alcohol is a drug known to impair the ability to drive safely and is acknowledged
      as a major factor in New Zealand road crashes. However, the use of other
      impairing drugs by New Zealand drivers is largely unknown. This paper reports the
      prevalence of drug use by drivers killed on New Zealand roads. As this is a
      biased population sample the results can only indicate possible drug use in the
      wider driving population. Blood samples taken from 1046 deceased drivers were
      analysed for the presence of alcohol and a range of both illicit drugs and
      psychoactive medicinal drugs. Five hundred and forty-six (52%) of these drivers
      had not used alcohol or other potentially impairing drugs. Five hundred (48%) had
      alcohol and/or other drugs in their blood that may have impaired their ability to
      drive safely. Of these 500 drivers, 135 had used alcohol alone, 96 had used
      cannabis alone and 142 had used a combination of alcohol and cannabis, but no
      other drug. Alcohol concentrations in 351 drivers who had drunk alcohol ranged
      from 5 to 354 mg per 100 mL (mean 152 mg/100 mL). Levels of tetrahydrocannabinol
      (THC) in the blood of the 314 drivers who had used cannabis ranged from
      approximately 0.1 ng/mL to 44 ng/mL (mean 5.6 ng/mL). There were 127 drivers who
      had used some other combination of drugs, many still including alcohol and/or
      cannabis. Only 29 of the 500 drivers who had used a drug, had not used either
      cannabis or alcohol and 240 (48%) of the 500 drivers had used more than one
      potentially impairing drug.

PMID- 23131306
TI  - Distribution of Aconitum alkaloids in autopsy cases of aconite poisoning.
AB  - Aconite is a well-known toxic-plant containing Aconitum alkaloids such as
      aconitines, benzoylaconines, and aconins. We describe here the distribution of
      Aconitum alkaloids detected by liquid chromatography-tandem mass spectrometry
      (LC/MS/MS) in three autopsy cases of suicide by aconite poisoning. Case 1: a male
      in his fifties had eaten aconite leaves. The concentrations of jesaconitine in
      cardiac blood, urine, and kidney were 12.1 ng/ml, 993.0 ng/ml, and 114.2 ng/g,
      respectively. Case 2: a female in her fifties had eaten aconite root. The aconite
      root in the stomach included a high level of mesaconitine. The concentrations of
      mesaconitine in cardiac blood, liver, and kidney were 69.1 ng/ml, 960.9 ng/g, and
      776.9 ng/g, respectively. Case 3: a male in his sixties had drunk liquor in which
      aconite root had been soaked. The concentrations of mesaconitine and aconitine in
      cardiac blood were 259.5 and 228.5 ng/ml, respectively. The Aconitum alkaloid
      levels were very high in the liver. The absorption of ethanol and Aconitum
      alkaloids might have been increased because of his having undergone total
      gastrectomy. In all three cases, the Aconitum alkaloid levels were high in the
      liver and kidney and low in the heart and cerebrum. The level in the cerebrum was
      lower than that in blood. Data on the distribution of the Aconitum alkaloids in
      the body in cases of aconite poisoning is useful to elucidate various actions of
      aconite alkaloids.

PMID- 23131307
TI  - Sertraline concentrations and postmortem redistribution.
AB  - Sertraline is a commonly prescribed selective inhibitor of serotonin uptake used
      for the treatment of mental depression and anxiety. Central blood and liver
      concentrations of sertraline (norsertraline) are compared to levels in peripheral
      blood in nine medical examiner cases. Specimens were initially screened for
      alcohol and simple volatiles by GC-FID headspace analysis, ELISA for drugs of
      abuse, and alkaline drugs by GC/MS. Sertraline, when detected by the alkaline
      drug screen, was subsequently confirmed and quantified by a specific GC-NPD
      procedure. Data suggest that when ingested with other medications, sertraline may
      be a contributing factor in death. Sertraline (norsertraline) concentrations
      ranged from 0.13 (0.11) to 2.1 (6.0) mg/L in peripheral blood, from 0.18 (0.12)
      to 2.0 (6.7) mg/L in central blood, and 21 to 160 mg/kg in liver. Sertraline
      central blood to peripheral blood ratios averaged 1.22+/-0.85 (mean+/-standard
      deviation). The liver to peripheral blood ratios, on the other hand, were
      markedly higher and averaged 97+/-40 (mean+/-standard deviation). Given that a
      liver to peripheral blood ratio exceeding 20 is indicative of propensity for
      significant postmortem redistribution, these data confirm that sertraline is
      prone to marked postmortem redistribution.

PMID- 23131308
TI  - Which serial killers commit suicide? An exploratory study.
AB  - In a sample of 483 serial killers, 6.2% were documented to have committed
      suicide. Those who committed suicide were found to come from more dysfunctional
      homes characterized by more psychiatric disturbance in the parents. The sexual
      acts involved in the murders by the suicides seemed to be more deviant in some
      aspects, such as committing more bizarre sexual acts or more often taping the
      murder.

PMID- 23131309
TI  - [Thymic epithelial neoplasms: updates on diagnosis, staging, biology and
      management in France].
AB  - Thymic epithelial neoplasms are rare malignancies with about 250 new incident
      cases in France every year. The WHO histologic classification distinguishes
      thymoma and thymic carcinoma which are tumors with different biological and
      clinical behaviors and outcomes. The Masaoka-Koga staging system is considered as
      a reference and is also of prognosis value. Diagnosis, multimodal treatment and
      follow-up of thymic epithelial neoplasms require a multidisciplinary approach
      where surgery is the cornerstone treatment. A national expert center coordinates
      thymic epithelial neoplasms management with 12 other regional expert centers
      through the French organization named RYTHMIC (www.rythmic.org). Patient's files
      have to be discussed at regional or national multidisciplinary staff. A group of
      expert pathologists will centrally review tumors when the diagnosis or
      classification is a matter of controversy. Among its objectives, RYHTMIC has to
      promote medical education, patient's information and research. This review
      focuses on RYTHMIC guidelines and data regarding multimodal management and
      targeted therapies in epithelial thymic neoplasms.

PMID- 23131310
TI  - Effect of solvents and oil content on direct transesterification of wet oil
      bearing microalgal biomass of Chlorella vulgaris ESP-31 for biodiesel synthesis
      using immobilized lipase as the biocatalyst.
AB  - In this work, a one-step extraction/transesterification process was developed to
      directly convert wet oil-bearing microalgal biomass of Chlorella vulgaris ESP-31
      into biodiesel using immobilized Burkholderia lipase as the catalyst. The
      microalgal biomass (water content of 86-91%; oil content 14-63%) was pre-treated
      by sonication to disrupt the cell walls and then directly mixed with methanol and
      solvent to carry out the enzymatic transesterification. Addition of a sufficient
      amount of solvent (hexane is most preferable) is required for the direct
      transesterification of wet microalgal biomass, as a hexane-to-methanol mass ratio
      of 1.65 was found optimal for the biodiesel conversion. The amount of methanol
      and hexane required for the direct transesterification process was also found to
      correlate with the lipid content of the microalga. The biodiesel synthesis
      process was more efficient and economic when the lipid content of the microalgal
      biomass was higher. Therefore, using high-lipid-content microalgae as feedstock
      appears to be desirable.

PMID- 23131311
TI  - Anaerobic digestibility of the waste activated sludge discharged from large-scale
      membrane bioreactors.
AB  - Anaerobic digestibility of the waste activated sludge (WAS) discharged from large
      scale membrane bioreactors (MBRs) and conventional activated sludge processes
      (CASs) were compared using batch trials. Four wastewater treatment plants were
      sampled. Results showed that the sludge from MBRs had poor anaerobic
      digestibility as it had lower volatile solid (VS) reduction rate and lower
      maximum biogas production rate. The partial sludge stabilization during the long
      sludge retention time (SRT) typically applied in MBRs was the possible reason. On
      the other hand, the difference in wastewater composition had a great impact on
      the properties of activated sludge and the downstream sludge digestion. Inorganic
      matter accumulation in the WAS may hinder the access of microorganisms to
      substrate. The humic-like substances accumulating in the activated sludge was
      expected to contribute to the worse digestibility and these substances were
      observed to be released during anaerobic digestion through three-dimensional
      excitation-emission matrix (EEM) fluorescence spectra.

PMID- 23131312
TI  - Oxidative stability of waste cooking oil and white diesel upon storage at room
      temperature.
AB  - Renewable diesel fuels are alternative fuels produced from vegetable oils or
      animal fats. Catalytic hydrotreating of waste cooking oil (WCO) was carried out
      at pilot-plant scale and a paraffinic diesel, called "white" diesel was obtained.
      The white diesel and WCO samples were stored for one year at room temperature
      under normal atmospheric conditions, but not exposed to sunlight. Viscosity,
      total acid number (TAN), induction period (IP), carbonaceous deposits, density,
      cold flow properties, distillation and water content were monitored. TAN and
      density of the white diesel stored in conventional bottles changed from 0 to
      0.221 mg KOH/g and from 787 to 838 kg/m(3), respectively. The remaining
      parameters did not vary significantly. Water content of WCO increased from 482 to
      2491 mg/kg, TAN from 0.744 to 0.931 mg KOH/g, whereas viscosity, IP and carbon
      residues fluctuated mildly. The results are indicative of the white diesel's
      stability, rendering it suitable for prolonged storage.

PMID- 23131313
TI  - [Diagnosis and treatment of leprous neuropathy in practice].
AB  - Leprosy still affects 240,000 persons every year in the world. It is a
      particularly common cause of neuropathy and severe disabilities in developing
      countries. With increasing migration, new cases of leprosy are regularly
      diagnosed in developed countries, where it still remains rare and so
      underestimated. Cutaneo-nevritic leprosy is the most frequent form of leprosy. It
      may be diagnosed by the clinical features and the cutaneous histology and
      bacteriology. Neuritic leprosy without obvious skin lesions is reported in 5 to
      15% of leprosy patients. It must be suspected in persons from areas of endemic
      disease presenting with nerve thickening and associated nerve deficit. Nerve
      biopsy is essential for diagnosis. However search for bacilli in cutaneous
      samples may be of great help and avoid nerve biopsy. Acute and severe neuritis
      occurs during reactional states, reversal reaction (Type 1) and erythema nodosum
      leprosum (Type 2). Multidrug therapy is advocated. The treatment of acute
      neuropathy needs a supplementary medical and sometimes surgical treatment.

PMID- 23131314
TI  - The psychopathological spectrum of Gilles de la Tourette syndrome.
AB  - Gilles de la Tourette syndrome (GTS) holds a unique status as quintessentially
      neuropsychiatric condition at the interface between neurology (movement disorder)
      and psychiatry (behavioural condition). This is a reflection of the common
      observation that the vast majority of patients present with behavioural problems
      in association with the motor and vocal tics which define GTS. The present
      article focuses on the relationship between GTS and obsessive-compulsive disorder
      (OCD), attention-deficit and hyperactivity disorder (ADHD), affective disorders
      (both major depression and bipolar affective disorder), and personality
      disorders. Over the last decade, converging lines of research have pointed
      towards the concept of a 'GTS spectrum', encompassing motor phenomena and
      behavioural symptoms, with important implications for the clinical management of
      patients.

PMID- 23131315
TI  - Genetic damage and lipid peroxidation in workers occupationally exposed to
      organic bentonite particles.
AB  - OBJECTIVES: It has been found that bentonite particles (BPs) could induce the
      cyto-genotoxicity and oxidative stress in vitro, but these effects on population
      exposed to BPs remain unclear. The aim of the present study was to investigate
      whether the genetic damage and lipid peroxidation can be detected in workers
      occupationally exposed to organic BPs. METHODS: Sixty subjects were divided into
      three groups: (i) exposure group I consisted of 20 workers exposed to high
      concentrations of organic BPs in air; (ii) exposure group II were composed of 20
      workers exposed to moderate concentrations of organic BPs in air; (iii) control
      group included 20 healthy unexposed subjects. Genetic damage was examined by
      comet assay and cytokinesis-block micronucleus cytome (CBMNcyt) assay. Lipid
      peroxidation was detected by malondialdehyde (MDA) assay. RESULTS: The % tail
      DNA, MDA, the frequencies of micronucleus (MNF), micronucleated cell (MCF),
      nucleoplasmic bridges (NPBs), nuclear buds (NBUDs), apoptotic cell rate (ACR) and
      necrotic cell rate (NCR) in two exposure groups were significantly higher than
      those in control group (P<0.01 or P<0.05). Moreover, the % tail DNA, MDA, MNF,
      MCF, NPBs, NBUDs, ACR and NCR in exposure group I with higher exposure level of
      organic BPs in air were significantly higher than those in exposure group II with
      lower level of organic BPs (P<0.01). The order of nuclear division index (NDI)
      was: exposure group I<exposure group II<control group. Correlation analysis
      showed that there were good correlations among the above nine parameters
      (P<0.01). Age had a significant effect on genetic damage in controls. CONCLUSION:
      The genetic damage and lipid peroxidation are detectable in population
      occupationally exposed to organic BPs, which may be influenced by the air
      exposure concentrations of organic BPs.

PMID- 23131317
TI  - Population data of the AmpFlSTR(r) NGMTM loci in South Portuguese population.
AB  - Allele frequencies and other relevant forensic parameters for 15 loci studied
      with AmpFlSTR(R) NGMTM kit were calculated in a population of individuals
      residing in the south of Portugal. Blood stain samples were obtained from a total
      of 452 unrelated individuals involved in paternity testing casework. The kit has
      five loci - D10S1248, D22S1045, D2S441, D1S1656 and D12S391 not present in any
      other kit used in our laboratory (Powerplex 16 System and Identifiler Plus). In
      our laboratory, this new kit is used as a screening tool to solve deficient cases
      as fatherless paternity test, and to help in paternity investigations with only
      one genetic incompatibility after the use of routine seventeen loci. Furthermore,
      this five loci included in the European Standard Set are also recommended by the
      European Network of Forensic Science Institutes "ENFSI" and the European DNA
      Profiling group "EDNAP". These studies are necessary to calculate statistical
      forensic parameters such as power of discrimination, power of exclusion, minimum
      allele frequency. Statistical parameters such as heterozigoty, homozigoty and
      combined power of exclusion were determinated. This kind of study is part of the
      Quality Program for Certificated Forensic Laboratories.

PMID- 23131316
TI  - Genetic polymorphism of 15 STR loci in Chinese Han population from Shanghai
      municipality in East China.
AB  - The aim of this study was to estimate the allelic frequencies of the fifteen STRs
      included in AmpFlSTR((r)) Identifiler((r)) PCR Amplification Kit (Applied
      Biosystems, USA) in a sample of 186 unrelated individuals resident in Shanghai.
      Allelic frequencies and forensic parameters were calculated. All loci showed no
      departure from Hardy-Weinberg equilibrium. The obtained frequencies were compared
      with other previously reported population data.

PMID- 23131318
TI  - A new customized artificial iris diaphragm for treatment of traumatic aniridia.
AB  - We report the use of a custom hand painted iris implant, which offers outstanding
      cosmetic results in the treatment of aniridia. In the past artificial Irides has
      been a poor match to the healthy eye and of limited cosmetic benefit. This
      artificial iris produced by Dr. Schmidt Intraocularlinsen GmbH, Germany is fully
      customized with handmade colour composition, which structurally matches the
      appearance of natural iris restoring the aesthetic appearance with higher patient
      satisfaction. CONCLUSION: Custom made artificial iris is an excellent product,
      which gives patients a cosmetically normal looking eye and better quality of
      life.

PMID- 23131319
TI  - Recurrent keratitis due to 'lost' contact lenses.

PMID- 23131320
TI  - Parabens: a real hazard or a scare story?
AB  - Parabens belong to a family of preservatives that are widely used, particularly
      in the cosmetic, pharmaceutical and food industries. Four esters are commonly
      used: methyl, ethyl, propyl and butyl parabens. They are either used alone or,
      for better efficacy, in the form of a mixture. They have been the target of a
      media smear campaign since 2005. Several studies have failed to formally prove
      their alleged responsibility in the occurrence of breast cancer. At recommended
      concentrations, methyl and ethyl parabens have no hormonal effect in humans.
      Propyl and butyl parabens are still being investigated as regards their effects
      on fertility in men exposed during early childhood. Parabens are well-known for
      having weak sensitising properties and for their absence of toxicity whereas new
      substitution products, not as well-known, may lead to new cases of contact
      allergy.

PMID- 23131321
TI  - Modified laryngotracheal separation for intractable aspiration pneumonia in
      patients with nasopharyngeal carcinoma treated by radiotherapy.
AB  - OBJECTIVES: Intractable aspiration pneumonia in patients with post
      radiotherapeutic nasopharyngeal carcinoma (PNC) is a formidable complication, but
      has not attracted enough attention in clinical practice. Modified laryngotracheal
      separation (MLTS) was applied for these patients in our hospital, the surgical
      effects of which were assessed. PATIENTS AND METHODS: Retrospective analysis of 9
      PNC cases complicated by intractable aspiration pneumonia in our hospital was
      carried out. All cases were diagnosed as lower cranial nerve palsy. Their
      aspiration pneumonia was not effectively prevented or controlled after a series
      of previous treatments, including active anti-infectives, neurotrophy,
      acupuncture, nutrition support, nasogastric feeding and tracheotomy. Ultimately
      all of them received modified laryngotracheal separation (MLTS) surgery. Efficacy
      of the operation was assessed. RESULTS: In all patients, aspiration pneumonia was
      effectively controlled after the operation, body weights increased more than 6kg
      six months later, and nutrition status, swallowing function and quality of life
      were all improved. CONCLUSIONS: Intractable post-radiotherapeutic aspiration
      pneumonia in patients with nasopharyngeal carcinoma was possibly caused by lower
      cranial nerve palsy, which might be related to radiation fields overlapped.
      Modified laryngotracheal separation is effective in eliminating intractable
      aspiration in PNC. Suitable patients should be carefully selected although the
      procedure is potentially reversible.

PMID- 23131323
TI  - Confronting the "r" word.

PMID- 23131324
TI  - Cost effectiveness in clinical screening.

PMID- 23131325
TI  - Patient requests for nonindicated care.

PMID- 23131326
TI  - Rationing treatments based on their cost per QALY.

PMID- 23131328
TI  - AMA Code of Medical Ethics' opinions on allocating medical resources.

PMID- 23131327
TI  - Teaching resource allocation--and why it matters.

PMID- 23131329
TI  - Identifying bedside rationing.

PMID- 23131330
TI  - Diagnosing acute low back pain.

PMID- 23131331
TI  - ERISA's effect on claims of injury due to denial of coverage.

PMID- 23131332
TI  - Oregon's experiment with prioritizing public health care services.

PMID- 23131333
TI  - How comparative effectiveness research feeds into cost-benefit analyses.

PMID- 23131334
TI  - What is a life worth?

PMID- 23131335
TI  - The other limited resource--time with patients.

PMID- 23131337
TI  - Modified multi-element synthetic transmit aperture method for ultrasound imaging:
      A tissue phantom study.
AB  - The paper presents the modified multi-element synthetic transmit aperture (MSTA)
      method for ultrasound imaging. It is based on coherent summation of RF echo
      signals with apodization weights taking into account the finite size of the
      transmit subaperture and of the receive element. The work presents extension of
      the previous study where the modified synthetic transmit aperture (STA) method
      was considered and verified [1]. In the case of MSTA algorithm the apodization
      weights were calculated for each imaging point and all combinations of the
      transmit subaperture and receive element using their angular directivity
      functions (ADFs). The ADFs were obtained from the exact solution of the
      corresponding mixed boundary-value problem for periodic baffle system modeling
      the transducer array. Performance of the developed method was tested using Field
      II simulated synthetic aperture data of point reflectors for 4MHz 128-element
      transducer array with 0.3mm pitch and 0.02mm kerf to estimate the visualization
      depth and lateral resolution. Also experimentally determined data of the tissue
      mimicking phantom (Dansk Fantom Service, model 571) obtained using 128 elements,
      4MHz, linear transducer array (model L14-5/38) and Ultrasonix SonixTOUCH Research
      platform were used for qualitative assessment of imaging contrast improvement.
      Comparison of the results obtained by the modified and conventional MSTA
      algorithms indicated 15dB improvement of the noise reduction in the vicinity of
      transducer's surface (1mm depth), and concurrent increase in the visualization
      depth (86% augment of the scattered amplitude at the depth of 90mm). However,
      this increase was achieved at the expense of minor degradation of the lateral
      resolution of approximately 8% at the depth of 50mm and 5% at the depth of 90mm.

PMID- 23131338
TI  - Angucyclines from an insect-derived actinobacterium Amycolatopsis sp. HCa1 and
      their cytotoxic activity.
AB  - One new angucyclinone derivative, amycomycin A (1), and one new angucycline,
      amycomycin B (2), along with 5 known compounds (3-7), were isolated from an
      actinobacterium Amycolatopsis sp. HCa1 associated with the grasshopper, Oxya
      chinensis. Their structures were elucidated on the basis of spectroscopic
      methods, including extensive NMR spectra. Compounds 1-7 were tested in vitro for
      their cytotoxic effects on five cell lines including human gastric adenocarcinoma
      cell line (BGC823), human hepatocarcinoma cell line (HepG2), human melanoma cell
      line (A375), human oral squamous carcinoma cell line (KB), and ghost cell line
      (Ghost-R5X4). Cell viability assays showed that compound 7 was active in four
      cell lines with IC(50) values less than 18.0 MUM except in KB showing no activity
      up to 100 MUM.

PMID- 23131339
TI  - Synthesis of novel MT3 receptor ligands via an unusual Knoevenagel condensation.
AB  - New 5-acetamido-substituted melatonin derivatives were efficiently synthesized in
      excellent yields via Knoevenagel condensation. The relative binding affinity of
      new synthesized compounds to MT3 receptor was tested via enzymatic assays and the
      X-ray structures of the most potent compounds were determined in complex with
      MT3.

PMID- 23131340
TI  - Development of sub-nanomolar dipeptidic ligands of neuropeptide FF receptors.
AB  - Based on our earlier reported neuropeptide FF receptors antagonist (RF9), we
      carried out an extensive structural exploration of the N-terminus part of the
      amidated dipeptide Arg-Phe-NH(2) in order to establish a structure-activity
      relationships (SAR) study towards both NPFF receptor subtypes. This SAR led to
      the discovery of dipeptides (12, 35) with subnanomolar affinities towards NPFF1
      receptor subtype, similar to endogenous ligand NPVF. More particularly, compound
      12 exhibited a potent in vivo preventive effect on opioid-induced hyperalgesia at
      low dose. The significant selectivity of 12 toward NPFF1-R indicates that this
      receptor subtype may play a critical role in the anti-opioid activity of NPFF
      like peptides.

PMID- 23131341
TI  - Synthesis of novel triplet drugs with 1,3,5-trioxazatriquinane skeletons and
      their pharmacologies. 3: synthesis of novel triplet drugs with the
      bis(epoxymethano) or bis(dimethylepoxymethano) structure (double-capped triplet).
AB  - Novel double-capped triplet drugs, which have one pharmacophore unit and two
      epoxymethano or dimethylepoxymethano structures (termed cap or diMe-cap
      structures, respectively) were synthesized. Key intermediate oxazoline 16 derived
      from acetone enabled the effective synthesis of double-capped triplets. SYK-134
      (7a) and SYK-135 (8a) with N-cyclopropylmethyl substituent and cap structures
      showed selectivities for the kappa opioid receptor. On the other hand, the N-Me
      series exhibited selectivities for the MU opioid receptor. The double-capped
      triplet drugs with diMe-cap structures preferred the MU receptor independently of
      their N-substituents. SYK-385 (19b), one of the MU-selective double-capped
      triplet drugs, showed the highest selectivity for the MU receptor among the
      reported MU-selective nonpeptide ligands.

PMID- 23131342
TI  - Discovery of a novel non-steroidal GR antagonist with in vivo efficacy in the
      olanzapine-induced weight gain model in the rat.
AB  - We report the optimization of a series of non-steroidal GR antagonists that led
      to the identification of compound 7. This compound is efficacious when dosed
      orally in an olanzapine-induced weight gain model in rats.

PMID- 23131344
TI  - Promises, delivery, and challenges of inflammatory bowel disease risk gene
      discovery.
AB  - Over the past two decades, investigators have used whole genome linkage and
      genome-wide association studies, including the "Immunochip" study, to identify a
      surprising number (over 163) of genetic loci containing susceptibility genes for
      inflammatory bowel disease (IBD) and its 2 major phenotypes, Crohn's disease (CD)
      and ulcerative colitis (UC). These loci, although nearly all low-risk, have
      provided important lessons regarding the nature of IBD etiopathogenesis,
      including that most loci cause both CD and UC risk; one-third of loci have risk
      for other common autoimmune diseases; numerous loci contain genes that regulate
      immunity to microbes; Th17 cells are disproportionately influenced by genes
      within IBD loci; and the HLA region influences UC far greater than CD.
      Interleukin-10 receptor subunit (IL10RA and IL10RB) and IL10 cytokine gene
      mutations cause a rare, severe, infantile-onset, autosomal recessive CD, and this
      knowledge has allowed curative treatment by bone marrow transplant. Key tasks for
      broader clinical translation include discovery of risk variants for non-white
      populations; discovery of the less frequent but higher penetrance and familial
      risk variants by next-generation sequencing; and determining which of numerous
      associated variations within loci result in specific gene dysfunction causing IBD
      risk-as only a small number of genes within IBD loci, including NOD2, IL23R,
      ATG16L1, IRGM, and PTPN22 have specific functional variations characterized.
      Studying the effect of IBD susceptiblity gene dysfunctions in tissue cultures and
      animal models will allow the ultimate translational benefits of developing novel
      treatments for and potentially preventing IBD in those having specific genetic
      risk factors.

PMID- 23131343
TI  - Manganese inhibits ATP-induced calcium entry through the transient receptor
      potential channel TRPC3 in astrocytes.
AB  - Chronic exposure to elevated levels of manganese (Mn(2+)) causes neuronal injury
      and inflammatory activation of glia. Astrocytes selectively accumulate Mn(2+),
      which inhibits mitochondrial respiration and increases production of reactive
      oxygen species. We previously reported that sub-acute exposure to low micromolar
      levels of Mn(2+) in primary astrocytes inhibited ATP-induced calcium (Ca(2+))
      signaling, associated with decreased levels of endoplasmic reticulum Ca(2+) and
      increased mitochondrial Ca(2+) loads. In the present studies, we postulated that
      the mechanism underlying the capacity of Mn(2+) to inhibit these purinergic
      signals in astrocytes could be due to competition with Ca(2+) for entry through a
      plasma membrane channel. These data demonstrate that acutely applied Mn(2+)
      rapidly inhibited ATP-induced Ca(2+) waves and transients in primary striatal
      astrocytes. Mn(2+) also decreased influx of extracellular Ca(2+) induced by 1
      oleoyl-2-acetyl-sn-glycerol (OAG), a direct activator of the transient receptor
      potential channel, TRPC3. The TRPC3 inhibitor, pyrazole-3, prevented ATP- and OAG
      dependent transport of Mn(2+) from extracellular stores, demonstrated by a
      dramatic reduction in the rate of fluorescence quenching of Fura-2. These data
      indicate that Mn(2+) can acutely inhibit ATP-dependent Ca(2+) signaling in
      astrocytes by blocking Ca(2+) entry through the receptor-operated cation channel,
      TRPC3. Loss of normal astrocytic responses to purinergic signals due to
      accumulation of Mn(2+) could therefore comprise critical homeostatic functions
      necessary for metabolic and trophic support of neurons.

PMID- 23131345
TI  - Starvation ketoacidosis in pregnancy.
AB  - Starvation ketosis outside pregnancy is rare and infrequently causes a severe
      acidosis. Placental production of hormones, including glucagon and human
      placental lactogen, leads to the insulin resistance that is seen in pregnancy,
      which in turn increases susceptibility to ketosis particularly in the third
      trimester. Starvation ketoacidosis in pregnancy has been reported and is usually
      precipitated by a period of severe vomiting. Ketoacidosis is likely to have
      important implications for fetal survival as ketoacidosis in women with type 1
      diabetes mellitus is associated with intrauterine death. This article features
      four cases of women with vomiting in the third trimester of pregnancy associated
      with a severe metabolic acidosis. The mechanism underlying ketogenesis, the
      evidence for accelerated ketogenesis in pregnancy and other similar published
      cases are reviewed. A proposed strategy for management of these women is
      presented.

PMID- 23131346
TI  - Determination, validation and standardization of a CMV DNA cut-off value in
      plasma for preemptive treatment of CMV infection in solid organ transplant
      recipients at lower risk for CMV infection.
AB  - BACKGROUND: Valganciclovir preemptive therapy guided by the viral load is the
      current strategy recommended for preventing CMV disease in CMV-seropositive Solid
      Organ Transplant Recipients (SOTR) at lower risk for developing CMV infection.
      However, universal viral load cut-off has not been established for initiating
      therapy. OBJECTIVES: Our goal was to define and validate a standardized cut-off
      determined in plasma by real-time PCR assay for initiating preemptive therapy in
      this population. STUDY DESIGN: A prospective cohort study of consecutive cases of
      CMV-seropositive SOTR was carried out. The cut-off value was determined in a
      derivation cohort and was validated in the validation cohort. Viral loads were
      determined using the Quant CMV LightCycler 2.0 real-time PCR System (Roche
      Applied Science) and results were standardized using the WHO International
      Standard for human CMV. RESULTS: A viral load of 3983 IU/ml (2600 copies/ml) was
      established as the optimal cut-off for initiating preemptive therapy in a cohort
      of 141 patients with 982 tests and validated in a cohort of 252 recipients with a
      total of 2022 test. This cut-off had a 99.6% NPV indicating that the great
      majority of patients at lower risk will not develop CMV disease without specific
      antiviral therapy. The high sensitivity and specificity (89.9% and 88.9%,
      respectively) and the relatively small numbers of patients with CMV disease
      confirm that real-time PCR was optimal. CONCLUSIONS: We have established a cut
      off viral load for starting preemptive therapy for CMV-seropositive SOT
      recipients. Our results emphasized the importance of a mandatory follow-up
      protocol for CMV-seropositive patients receiving preemptive treatment.

PMID- 23131347
TI  - Tinea corporis bullosa due to Microsporum canis mimicking linear IgA bullous
      dermatosis.

PMID- 23131348
TI  - Guidance is needed on inhaled glucocorticoids and acute adrenal crises.

PMID- 23131349
TI  - PRRT2 mutation in Japanese children with benign infantile epilepsy.
AB  - Mutations in PRRT2 genes have been identified as a major cause of benign
      infantile epilepsy and/or paroxysmal kinesigenic dyskinesia. We explored
      mutations in PRRT2 in Japanese patients with BIE as well as its related
      conditions including convulsion with mild gastroenteritis and benign early
      infantile epilepsy. We explored PRRT2 mutations in Japanese children who had had
      unprovoked infantile seizures or convulsion with mild gastroenteritis. The
      probands included 16 children with benign infantile epilepsy, 6 children with
      convulsions with mild gastroenteritis, and 2 siblings with benign early infantile
      epilepsy. In addition, we recruited samples from family members when PRRT2
      mutation was identified in the proband. Statistical analyses were performed to
      identify differences in probands with benign infantile epilepsy according to the
      presence or absence of PRRT2 mutation. Among a total of 24 probands, PRRT2
      mutations was identified only in 6 probands with benign infantile epilepsy. A
      common insertion mutation, c.649_650insC, was found in 5 families and a novel
      missense mutation, c.981C>G (I327M), in one. The family history of paroxysmal
      kinesigenic dyskinesia was more common in probands with PRRT2 mutations than in
      those without mutations. Our study revealed that PRRT2 mutations are common in
      Japanese patients with benign infantile epilepsy, especially in patients with a
      family history of paroxysmal kinesigenic dyskinesia. 

PMID- 23131351
TI  - Reduced expression of Autographa californica nucleopolyhedrovirus ORF34, an
      essential gene, enhances heterologous gene expression.
AB  - Autographa californica multiple nucleopolyhedrovirus ORF34 is part of a
      transcriptional unit that includes ORF32, encoding a viral fibroblast growth
      factor (FGF) and ORF33. We identified ORF34 as a candidate for deletion to
      improve protein expression in the baculovirus expression system based on enhanced
      reporter gene expression in an RNAi screen of virus genes. However, ORF34 was
      shown to be an essential gene. To explore ORF34 function, deletion (KO34) and
      rescue bacmids were constructed and characterized. Infection did not spread from
      primary KO34 transfected cells and supernatants from KO34 transfected cells could
      not infect fresh Sf21 cells whereas the supernatant from the rescue bacmids
      transfection could recover the infection. In addition, budded viruses were not
      observed in KO34 transfected cells by electron microscopy, nor were viral
      proteins detected from the transfection supernatants by western blots. These
      demonstrate that ORF34 is an essential gene with a possible role in infectious
      virus production.

PMID- 23131352
TI  - Abdominal wall incisional hernias: infected prosthesis: treatment and prevention.
AB  - In clean surgery (Altemeier Class I), the incidence of infections is not
      increased by the placement of prosthetic material. Prosthetic mesh infections
      occur more frequently and are more serious in ventral incisional repair than in
      inguinal hernia repair. While removal of the mesh resolves the infectious
      problem, it creates other problems that are equally difficult. This underscores
      the need to: explore other conservative hernia treatment options; in the end,
      these are often feasible; respect and implement strict measures to prevent
      infection.

PMID- 23131350
TI  - Pirates of the Caudovirales.
AB  - Molecular piracy is a biological phenomenon in which one replicon (the pirate)
      uses the structural proteins encoded by another replicon (the helper) to package
      its own genome and thus allow its propagation and spread. Such piracy is
      dependent on a complex web of interactions between the helper and the pirate that
      occur at several levels, from transcriptional control to macromolecular assembly.
      The best characterized examples of molecular piracy are from the E. coli P2/P4
      system and the S. aureus SaPI pathogenicity island/helper system. In both of
      these cases, the pirate element is mobilized and packaged into phage-like
      transducing particles assembled from proteins supplied by a helper phage that
      belongs to the Caudovirales order of viruses (tailed, dsDNA bacteriophages). In
      this review we will summarize and compare the processes that are involved in
      molecular piracy in these two systems.

PMID- 23131354
TI  - The clinical, professional, and social challenges of practicing rural medicine.

PMID- 23131353
TI  - Membrane configuration optimization for a murine in vitro blood-brain barrier
      model.
AB  - A powerful experimental tool used to study the dynamic functions of the blood
      brain barrier (BBB) is an in vitro cellular based system utilizing cell culture
      inserts in multi-well plates. Currently, usage of divergent model configurations
      without explanation of selected variable set points renders data comparisons
      difficult and limits widespread understanding. This work presents for the first
      time in literature a comprehensive screening study to optimize membrane
      configuration, with aims to unveil influential membrane effects on the ability of
      cerebral endothelial cells to form a tight monolayer. First, primary murine brain
      endothelial cells and astrocytes were co-cultured in contact and non-contact
      orientations on membranes of pore diameter sizes ranging from 0.4 MUm to 8.0 MUm,
      and the non-contact orientation and smallest pore diameter size were shown to
      support a significantly tighter monolayer formation. Then, membranes made from
      polyethylene terephthalate (PET) and polycarbonate (PC) purchased from three
      different commercial sources were compared, and PET membranes purchased from two
      manufacturers facilitated a significantly tighter monolayer formation. Models
      were characterized by transendothelial electrical resistance (TEER), sodium
      fluorescein permeability, and immunocytochemical labeling of tight junction
      proteins. Finally, a murine brain endothelial cell line, bEnd.3, was grown on the
      different membranes, and similar results were obtained with respect to optimal
      membrane configuration selection. The results and methodology presented here on
      high throughput 24-well plate inserts can be translated to other BBB systems to
      advance model understanding.

PMID- 23131355
TI  - The overlapping roles of the rural doctor.

PMID- 23131356
TI  - Rural primary care--working outside the comfort zone.

PMID- 23131357
TI  - Patient privacy and mental health care in the rural setting.

PMID- 23131358
TI  - Wisconsin Academy for Rural Medicine--an initiative to increase physician
      workforce in rural Wisconsin.

PMID- 23131359
TI  - Recognizing and resolving ethical dilemmas in rural medicine.

PMID- 23131360
TI  - Diagnosing rheumatoid arthritis.

PMID- 23131361
TI  - Ethical and regulatory considerations in prescribing RU-486.

PMID- 23131362
TI  - Federal and state initiatives to recruit physicians to rural areas.

PMID- 23131363
TI  - Balancing prestige with personal satisfaction and social need in specialty
      choice.

PMID- 23131364
TI  - Mumbai to Detroit to Huntington, West Virginia--a foreign medical graduate in
      rural America.

PMID- 23131365
TI  - A case for special programs to expand the ranks of rural physicians.

PMID- 23131367
TI  - Argentine tango dance compared to mindfulness meditation and a waiting-list
      control: a randomised trial for treating depression.
AB  - OBJECTIVES: To determine whether tango dancing is as effective as mindfulness
      meditation in reducing symptoms of psychological stress, anxiety and depression,
      and in promoting well-being. DESIGN: This study employed analysis of covariance
      (ANCOVA) and multiple regression analysis. PARTICIPANTS: Ninety-seven people with
      self-declared depression were randomised into tango dance or mindfulness
      meditation classes, or to control/waiting-list. SETTING: classes were conducted
      in a venue suitable for both activities in the metropolitan area of Sydney,
      Australia. INTERVENTIONS: Participants completed six-week programmes (11/2h/week
      of tango or meditation). The outcome measures were assessed at pre-test and post
      test. MAIN OUTCOME MEASURES: Depression, Anxiety and Stress Scale; The Self
      Esteem Scale; Satisfaction with Life Scale, and Mindful Attention Awareness
      Scale. RESULTS: Sixty-six participants completed the program and were included in
      the statistical analysis. Depression levels were significantly reduced in the
      tango (effect size d=0.50, p=.010), and meditation groups (effect size d=0.54,
      p=.025), relative to waiting-list controls. Stress levels were significantly
      reduced only in the tango group (effect size d=0.45, p=.022). Attending tango
      classes was a significant predictor for the increased levels of mindfulness
      R(2)=.10, adjusted R(2)=.07, F (2,59)=3.42, p=.039. CONCLUSION: Mindfulness
      meditation and tango dance could be effective complementary adjuncts for the
      treatment of depression and/or inclusion in stress management programmes.
      Subsequent trials are called to explore the therapeutic mechanisms involved.

PMID- 23131368
TI  - One year study on the integrative intervention of acupressure and interactive
      multimedia for visual health in school children.
AB  - OBJECTIVE: This study used a larger sample size, added a long-term observation of
      the effect of intervention, and provided an integrated intervention of
      acupressure and interactive multimedia of visual health instruction for school
      children. The short- and long-term effects of the interventions were then
      evaluated by visual health knowledge, visual acuity, and refractive error.
      DESIGN: A repeated pretest-posttest controlled trial was used with two
      experimental groups and one control group. SETTING: Four elementary schools in
      northern Taiwan. PARTICIPANTS: 287 School children with visual impairment in
      fourth grade were recruited. METHOD: One experimental group received the
      integrative intervention of acupressure and interactive multimedia of visual
      health instruction (ACIMU), and another received auricular acupressure (AC)
      alone; whereas a control group received no intervention. Two 10-week
      interventions were separately given in the fall and spring semesters. The short-
      and long-term effects of the interventions were then evaluated by visual health
      knowledge, visual acuity, and refractive error. RESULTS: During the school year
      the visual health knowledge was significantly higher in the ACIMU group than the
      control group (p<0.001). A significant difference in the changing visual acuity
      was in the three groups (p<0.001), with the improvement in the ACIMU group. No
      difference in the refractive error was found between any two groups (p>0.05).
      CONCLUSIONS: This study demonstrated that a long-term period of acupressure is
      required to improve school children's visual health. School children receiving
      the intervention of acupressure combined with interactive multimedia had better
      improvement of visual health and related knowledge than others. Further study is
      suggested in which visual health and preventative needs can be established for
      early childhood.

PMID- 23131369
TI  - Clinical utility of paced breathing as a concentration meditation practice.
AB  - OBJECTIVES: The present study examined changes in electroencephalogram (EEG) and
      heart rate variability (HRV) parameters during paced breathing (PB) and their
      relationships with self-reported personality traits. METHODS: Fifty-eight
      meditation-naive subjects (36 men, 22 women) ranging in age from 20 to 30 years
      completed the Temperament and Character Inventory (TCI). After a spontaneous
      breathing session, participants were asked to breathe in 6-s cycles, guided by an
      acoustic stimulus. EEG, HRV, and respiratory data were recorded during
      spontaneous and paced breathing. We calculated the powers for the EEG and HRV
      parameters based on the most regular respiratory curve observed over a 5-min
      period. RESULTS: In terms of HRV parameters, the high-frequency power increased
      and the low frequency-to-high frequency ratio decreased during PB. The low
      frequency power did not change. In terms of EEG parameters, low-frequency alpha
      power, a marker of internal attention, globally increased and theta power, a
      marker of an advanced meditative state, locally decreased. This indicates that
      parasympathetic activity and internal attention increased, whereas an advanced
      meditative state was inhibited during PB. Of the personality traits, harm
      avoidance, novelty seeking, persistence, self-directedness, and self
      transcendence were related to changes in low- and high-frequency alpha powers.
      CONCLUSIONS: Our results suggest that PB can be utilized as a concentration
      meditation practice for novices, and that individual differences such as
      personality traits should be considered when PB is offered for clinical or
      experimental purposes.

PMID- 23131370
TI  - The feasibility of aromatherapy massage to reduce symptoms of Idiopathic
      Environmental Intolerance: a pilot study.
AB  - OBJECTIVES: Idiopathic Environmental Intolerance (IEI) is an acquired disorder
      with multiple recurrent symptoms, which is associated with diverse environmental
      factors that are tolerated by the majority of people. IEI is an illness of
      uncertain aetiology, making it difficult to treat using conventional medicine.
      Therefore, there is a need for novel therapies to control the symptoms of IEI.
      The objective of this study was to evaluate the feasibility and impact of
      aromatherapy massage for individuals with IEI. DESIGN: Non-blinded crossover
      trial. SETTING: IEI patients who attended a clinic in Sapporo city were
      recruited, and sixteen patients were enrolled. Participants were clinically
      examined by an experienced medical doctor and met the criteria included in the
      working definition of IEI disorder. INTERVENTIONS: During the active period,
      participants received four one-hour aromatherapy massage sessions every two
      weeks. During the control period, the participants did not receive any massages.
      MAIN OUTCOME MEASUREMENTS: Scores on the IEI-scales trigger checklist, symptoms,
      life impact, and the State Anxiety Inventory were assessed before and after each
      period. Short-term mood enhancement was evaluated using the Profiles of Mood
      Status (POMS) before and after sessions. RESULTS: Due to period effects,
      evaluation of the results had to be restricted to the first period, and the
      result showed no effect of intervention. All six sub-scales of the POMS improved
      after each session (mean score differences: 4.89-1.33, P<0.05). CONCLUSIONS:
      Aromatherapy was well tolerated by subjects with IEI; however, aromatherapy, as
      applied in this study, did not suggest any specific effects on IEI condition.

PMID- 23131371
TI  - Monochord sounds and progressive muscle relaxation reduce anxiety and improve
      relaxation during chemotherapy: a pilot EEG study.
AB  - BACKGROUND: Chemotherapy is the most distressing form of cancer treatment in
      oncology, but listening to music can be an adjuvant during chemotherapy.
      Monochord (MC) sounds are used in music therapy for the alleviation of pain,
      enhanced body perception, and relaxation. This study investigated the relaxation
      effect of MC sounds for patients during chemotherapy compared with progressive
      muscle relaxation (PMR), an established relaxation technique.
      METHODOLOGY/PRINCIPAL FINDINGS: Two randomized groups of patients were observed
      during chemotherapy. One group listened to recorded MC sounds (n=20) and the
      other group listened to recorded PMR (n=20). Each session was investigated pre
      and post using Spielberger's State Anxiety Inventory (SAI) and a questionnaire
      about the patient's physical and psychological states. Further, for the first and
      the last session, multivariate electroencephalogram (EEG) signals were recorded.
      Patients in both MC and PMR groups showed significant improvement in their
      physical and psychological states and in state anxiety. The EEG data showed that
      the MC and the PMR groups were associated with an increase of posterior theta
      (3.5-7.5 Hz) and a decrease of midfrontal beta-2 band (20-29.5 Hz) activity
      during the end phase of relaxation treatment. Further, the MC group was
      associated with decreased alpha band (8-12 Hz) activity in comparison with PMR
      group. CONCLUSIONS: This study shows that both listening to recorded MC sounds
      and practising PMR have a useful and comparable effect on gynaecologic
      oncological patients during chemotherapy, with partially overlapping but also
      notably divergent neural correlates. Future research should establish the
      systematic use of MC in oncological contexts.

PMID- 23131372
TI  - The effect of acupressure on sleep quality in hemodialysis patients.
AB  - OBJECTIVE: Our purpose was to investigate the effects of acupressure on sleep
      quality in hemodialysis patients. DESIGN: Randomized clinical trial. SETTING: The
      setting of the study was dialysis wards located in two university hospitals (Imam
      and Golestan) in Ahvaz, Iran. INTERVENTIONS: 48 end-stage renal disease patients
      on hemodialysis who scored 5 points or higher on the Pittsburgh Sleep Quality
      Index (PSQI) were enrolled to the study. Acupressure group received acupressure
      intervention on the Shenmen (He7) and He Gu (Li4) points in the hands and
      Sanyingjao (sp6) point in the feet for 4 weeks beside routine care and control
      group received only routine care. MAIN OUTCOME MEASURES: subjective sleep
      quality, latency and duration, habitual sleep efficiency; sleep disturbances,
      daytime functional status, and use of sleeping medications. RESULTS: The result
      indicated significant differences between the acupressure group and the control
      group after intervention in PSQI global scores (p<0.001) and all sleep quality
      indices between two groups after intervention: subjective sleep quality
      (p<0.001), sleep latency (p<0.001), sleep duration (p<0.001), sleep efficiency
      (p=0.006), sleep disturbance (p<0.001), the use of sleeping medication (p=0.028),
      and daytime dysfunction (p<0.001). CONCLUSION: This study supports the
      effectiveness of acupressure in improving sleep quality of end-stage renal
      disease patients as a noninvasive therapy.

PMID- 23131373
TI  - Effect of integrated Yoga on neurogenic bladder dysfunction in patients with
      multiple sclerosis-A prospective observational case series.
AB  - BACKGROUND: Neurogenic bladder dysfunction (NBD) is a common distressful symptom
      in multiple sclerosis (MS) affecting quality of life. Yoga has been widely used
      in treating various symptoms of patients with MS. OBJECTIVES: To evaluate the
      effect of integrated Yoga for NBD in patients with MS as an adjunct to standard
      medical care. DESIGN: This open arm, pre-post study design assessed the outcome
      measures at base line and after 21 days of integrated Yoga intervention. SETTING:
      study was conducted at the center for neurological rehabilitation at KWA-Klinik
      Stift Rottal in Bad Griesbach, Germany. Eleven MS patients with NBD (mean age
      46.7+/-11.24 years) with mean duration 17.2 years volunteered to participate in
      the study. INTERVENTIONS: integrated Yoga which includes preparatory yogic
      loosening and breathing practices, Nadishuddi pranayama (alternate nostril
      breathing), moola bandha (anal lock), kapalbhati (rapid nostril breathing) and
      deep relaxation technique was given for 2h per day for continuous 21 days.
      OUTCOME MEASURES: ultrasound scanning for post void residual urine volume (PVR),
      micturition check list (MCL), incontinence impact questionnaire-7 (IIQ-7)
      andurogenital distress inventory-6 (UDI-6) were used. RESULTS: Paired sample t
      test showed significant improvement in post void residual urine (62.34%, p<0.05),
      scores on micturition frequency checklist (25%, p<0.05), incontinence impact
      questionnaire-7 (32.77%, p<0.05) and uro-genital distress inventory-6 (26.33%,
      p<0.05). CONCLUSION: This study points to the safety and effectiveness of
      integrated Yoga for bladder symptoms as an adjunct to standard care in multiple
      sclerosis patients with neurogenic bladder dysfunction in Germany. Further trails
      are necessary to confirm these findings.

PMID- 23131374
TI  - Traditional Chinese medicine speeds-up humerus fracture healing: two case
      reports.
AB  - OBJECTIVE: Two cases illustrate the potential benefit of traditional Chinese
      medicine (TCM) treatments on speeding-up proximal humeral fracture healing.
      CLINICAL FEATURES: The cases include two patients with traumatic right proximal
      humerus closed fracture, one who fell down while standing on a chair and the
      other hit by a moped. Alternative treatments had been applied to restore humerus
      fracture. They were treated with the same modality by acupuncture on LI4, LI10,
      LI1, LI15, LI16 and SI9, with occasional electroacupuncture at LI4 and LI16, as
      well as concomitant herbal formula powder prescription named "Zheng Gu Zi Jin
      Dan". Within 2 months treatment, both patients seemed to have speed-up bone
      healing. The Constant Score increased from 9 to 42 and 36, before and after
      acupuncture therapy. CONCLUSIONS: To our experience, the old patients' fracture
      had speed-up healing while under TCM treatments. This might hint that TCM
      treatments not only play a role in pain control, but also accelerate bone healing
      for certain fracture cases. Long-term follow-up and future experimental studies
      are warranted to examine the efficacy of TCM treatments for healing bone fracture
      in the elderly.

PMID- 23131375
TI  - Anti-tuberculosis activity of Indian grass KHUS (Vetiveria zizanioides L. Nash).
AB  - AIMS & OBJECTIVES: Vetiveria zizanioides L. Nash (Family: Poaceae) root (intact
      and spent) extracts and fractions were evaluated for antimycobacterial activity
      against Mycobacterium tuberculosis H(37)Rv and H(37)Ra strains using radiometric
      BACTEC 460 TB system. METHODS & RESULTS: The ethanolic extract of intact as well
      as spent root were showed potent antituberculosis activity at a minimum
      concentration of 500MUg/mL. The hexane fraction also showed antibacterial action
      by recording continuous decline in growth index (GI) of M. tuberculosis at
      50MUg/mL. It was furthermore observed that root extract and hexane fraction
      showed activity even after the extraction of essential oil by hydro-distillation.
      CONCLUSION: Our results suggest that ethanolic extract and hexane fraction
      exhibited potent antimycobacterial activity. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The observed potential inhibitory characteristic not only supports the
      traditional medicinal uses of vetiver but also signify a promising candidature of
      root extract and hexane fraction of V. zizanioides as an antituberculosis agent.

PMID- 23131376
TI  - A pilot study to evaluate nutritional influences on gastrointestinal symptoms and
      behavior patterns in children with Autism Spectrum Disorder.
AB  - BACKGROUND: One in 110 children in the US have autism spectrum disorder (ASD), a
      debilitating and life-long disorder that affects the health, relationships, and
      learning of affected children. Existing research on the etiology, contributing
      factors, and treatment for ASD is limited and controversial. Studies suggest that
      GI symptoms are related to behavior issues in children with ASD, which may be
      improved by a gluten-free, casein-free (GFCF) diet. OBJECTIVES: To evaluate the
      relationship between a GFCF diet and gastrointestinal symptoms and behavior
      patterns in children with ASD. DESIGN AND SETTING: Cross-sectional design in
      which parents completed an online survey regarding general health, diet (adapted
      food-frequency questionnaire (FFQ)), gastrointestinal symptoms, and behavior
      patterns of their children with ASD. MAIN OUTCOME MEASURES: Scores on the
      Gastrointestinal Symptoms Rating Scale (GSRS) and Childhood Autism Rating Scale
      (CARS). RESULTS: Seven of thirteen children (median age 9years) were on a GFCF
      diet, consuming significantly fewer gluten- and casein-containing foods than
      those not on a GFCF diet. GSRS and CARS scores did not differ significantly
      according to diet. Parents of all the children on a GFCF diet reported improved
      GI symptoms and behavior patterns. CONCLUSIONS: This study provides evidence that
      the adapted FFQ is an effective tool for evaluating adherence to a GFCF diet.
      Continued well-controlled research is necessary to elucidate the gut-brain
      relationship in ASD.

PMID- 23131377
TI  - Complementary and alternative medicine use in Turkish children with epilepsy.
AB  - We aimed to determine the prevalence, pattern of use, parental sources of
      information and adverse effects of complementary and alternative medicine (CAM)
      in children with epilepsy. Parents of children with epilepsy (n=305; mean age:
      8.3+/-4.3 years) were interviewed with structured open and close-ended
      questionnaire. Patients were divided in two groups, CAM and non-CAM and compared
      using statistical tests. The use of CAM was detected in 22.6% of the patients
      (n=69). Prayer was the most commonly used therapy in 91.3% of children (n=63).
      Gender (p=0.032, [OR]: 0.5, 95%CI: 0.287-0.945) and resistance to antiepileptic
      drugs (p=0.005, [OR]: 3.4, 95%CI: 1.459-8.148) were found to be associated with
      CAM use. Parental use of CAMs to treat their children with epilepsy is not common
      in the Eastern Blacksea Region of Turkey. The research findings have demonstrated
      that patients' parents trust in their doctors. However, male sex and the presence
      of resistance of anti epileptics are potentially CAM predictors.

PMID- 23131378
TI  - Acupuncture for cancer patients suffering from hiccups: a systematic review and
      meta-analysis.
AB  - OBJECTIVE: The objective of this review was to assess the effectiveness of
      acupuncture for treating hiccups in patients with cancer. METHOD: Thirteen
      databases were searched from their inception through July 2011 without language
      restrictions. Randomised clinical trials (RCTs) were included if acupuncture was
      used as the sole treatment or as a part of a combination therapy with
      conventional drugs for hiccups in cancer patients. Studies were included if they
      compared acupuncture to placebo, drug therapy or no treatment. Cochrane criteria
      were used to assess the risk of bias. RESULTS: A total of 5 RCTs met our
      inclusion criteria. All of the included RCTs were associated with a high risk of
      bias. The majority of studies suggested favourable effects of acupuncture
      compared with conventional treatments. A meta-analysis revealed superior response
      rates for acupuncture compared with intramuscular injections (n=162; RR, 1.87;
      95% CI 1.26-2.78; P=0.002; heterogeneity: chi(2)=3.16, P=0. 21, I(2)=37%).
      CONCLUSIONS: This systematic review provides very limited evidence for the
      effectiveness of acupuncture compared with the conventional therapy
      (intramuscular injections) for treating hiccups. The total number, as well as was
      the methodological quality, of the RCTs included in this review was low. Rigorous
      RCTs will be necessary in the future to test the efficacy of acupuncture for
      treating hiccups in cancer patients.

PMID- 23131379
TI  - A systematic review to evaluate the clinical benefits of craniosacral therapy.
AB  - OBJECTIVE: Craniosacral therapy (CST) is an alternative treatment approach,
      aiming to release restrictions around the spinal cord and brain and subsequently
      restore body function. A previously conducted systematic review did not obtain
      valid scientific evidence that CST was beneficial to patients. The aim of this
      review was to identify and critically evaluate the available literature regarding
      CST and to determine the clinical benefit of CST in the treatment of patients
      with a variety of clinical conditions. METHODS: Computerised literature searches
      were performed in Embase/Medline, Medline((r)) In-Process, The Cochrane library,
      CINAHL, and AMED from database start to April 2011. Studies were identified
      according to pre-defined eligibility criteria. This included studies describing
      observational or randomised controlled trials (RCTs) in which CST as the only
      treatment method was used, and studies published in the English language. The
      methodological quality of the trials was assessed using the Downs and Black
      checklist. RESULTS: Only seven studies met the inclusion criteria, of which three
      studies were RCTs and four were of observational study design. Positive clinical
      outcomes were reported for pain reduction and improvement in general well-being
      of patients. Methodological Downs and Black quality scores ranged from 2 to 22
      points out of a theoretical maximum of 27 points, with RCTs showing the highest
      overall scores. CONCLUSION: This review revealed the paucity of CST research in
      patients with different clinical pathologies. CST assessment is feasible in RCTs
      and has the potential of providing valuable outcomes to further support clinical
      decision making. However, due to the current moderate methodological quality of
      the included studies, further research is needed.

PMID- 23131380
TI  - The effect of red yeast rice (Monascus purpureus) in dyslipidemia and other
      disorders.
AB  - BACKGROUND: Red Yeast Rice (RYR) is a traditional Chinese food that is fermented
      and obtained after red yeast (Monascus purpureus) is grown on rice. RYR contains
      Monacolin K (Lovastatin) and other active ingredients that are thought to play a
      role in the management of cholesterol levels. Recently, many clinical trials have
      focused on the uses of RYR, including for dyslipidemia, coronary heart disease,
      diabetes, osteoporosis, cancer, non-alcoholic fatty liver disease, fatigue, and
      memory. OBJECTIVES: The primary objective of this review is to evaluate the
      effectiveness of RYR on the management of dyslipidemia. The secondary objective
      is to review studies that focus on the other uses of RYR. The following search
      terms were used: red yeast rice, Xuezhikang, Hypocol, Cholestin, Monascus
      purpureus combined with dyslipidemia, hypercholesterolemia, hyperlipidemia,
      lipid, cardiovascular, coronary, atherosclerosis, diabetes, sugar, bone,
      osteoporosis, liver, fatigue, memory, Alzheimer's, dementia. RESULTS: Studies
      reviewed show that RYR significantly lowered LDL cholesterol and total
      cholesterol. Effects on triglycerides and HDL cholesterol were also observed in
      some studies. Compared with statins, RYR was shown to have an equal efficacy to
      statins when combined with or without other dietary supplements. RYR also
      appeared to be superior to placebo in preventing nonfatal myocardial infarction,
      total coronary heart disease events, and total deaths. On the other hand,
      information on diabetes, osteoporosis, cancer, non-alcoholic fatty liver disease,
      fatigue, and memory are currently limited although in vivo and in vitro studies
      have shown an effect. CONCLUSION: Results of RYR clinical trials presented here
      have limitations and RYR's clinical use should be further investigated before
      using RYR as one of the alternative treatments for dyslipidemia management,
      despite the fact that the strongest evidence for RYR use is in dyslipidemia
      versus other clinical conditions.

PMID- 23131381
TI  - Environmental and economic assessment of a road safety product made with virgin
      and recycled HDPE: a comparative study.
AB  - The development of value-added products made from post-consumer plastic
      recyclates has become an important goal in the quest for a sustainable society.
      To attain such goal, tools with higher accuracy and wider scope are increasingly
      necessary. The present work describes the application of a Life Cycle Assessment
      (LCA)/Life Cycle Costing (LCC) integrated model, with inclusion of externalities
      (environmental and social costs), to Anti-Glare Lamellae (AGL) made with High
      Density Polyethylene (HDPE). It compares an AGL currently manufactured from
      virgin HDPE (current AGL) with an alternative one made with recycled HDPE
      (optional AGL). The results obtained show that neither the current nor the
      optional AGL depict the best environmental performance in all impact categories.
      Nevertheless, there is a clear overall environmental and economic advantage in
      replacing virgin HDPE with recycled HDPE. The present work also makes evident
      that the LCA/LCC integrated model allows the identification of economic and
      environmental win-win and trade-off situations related to the full life cycle of
      products. As such, its results can be used as valuable guidelines in product
      development.

PMID- 23131382
TI  - Learning an energy-demanding and biomechanically constrained motor skill,
      racewalking: movement reorganization and contribution of metabolic efficiency and
      sensory information.
AB  - This study investigated how novices learn an energy demanding and biomechanically
      constrained task like racewalking. The first aim was to examine if movement
      reorganizes according to some fundamental strategies, proceeding in different
      stages (Newell, 1985). The second aim was to investigate the link between
      movement reorganization, metabolic efficiency and perceived exertion. Seven
      participants undertook seven racewalking learning sessions on a motorized
      treadmill, with increased velocity as the experiment progressed, in order to
      reach a goal performance speed of 10 kmh(-1). Peripheral/central perceived
      exertion ratings, kinematic and metabolic data were collected during the 1st,
      4th, 6th and 7th session. Repeated-measures (Learning Session*Speed) ANOVAs on
      kinematic data showed a proximal-to-distal directional trend in movement
      reorganization, with significant practice-related changes in pattern coordination
      and decreased variability. Early movement reorganization occurred at the 1st
      session ("coordination stage") and progressed until the 4th session ("control
      stage") to reach a plateau. In contrast, metabolic efficiency and peripheral
      perceived exertion continued optimizing until the last session, probably
      occurring in concurrence with the control stage. Peripheral perceived exertion
      presented the highest correlation with the global movement reorganization
      variables suggesting that it could play a key role in guiding movement
      reorganization in the learning process, improving efficiency as a result.

PMID- 23131384
TI  - Necrotizing fasciitis of the breast and axillary regions.

PMID- 23131383
TI  - Mapping repetition suppression of the P50 evoked response to the human cerebral
      cortex.
AB  - OBJECTIVE: The cerebral network subserving repetition suppression (RS) of the P50
      auditory evoked response as observed using paired-identical-stimulus (S1-S2)
      paradigms is not well-described. METHODS: We analyzed S1-S2 data from electrodes
      placed on the cortices of 64 epilepsy patients. We identified regions with
      maximal amplitude responses to S1 (i.e., stimulus registration), regions with
      maximal suppression of responses to S2 relative to S1 (i.e., RS), and regions
      with no or minimal RS 30-80 ms post stimulation. RESULTS: Several temporal,
      parietal and cingulate area regions were shown to have significant initial
      registration activity (i.e., strong P50 response to S1). Moreover, prefrontal,
      cingulate, and parietal lobe regions not previously proposed to be part of the
      P50 habituation neural circuitry were found to exhibit significant RS.
      CONCLUSIONS: The data suggest that the neural network underlying the initial
      phases of the RS process may include regions not previously thought to be
      involved like the parietal and cingulate cortexes. In addition, a significant
      role for the frontal lobe in mediating this function is supported. SIGNIFICANCE:
      A number of regions of interest are identified through invasive recording that
      will allow further probing of the RS function using less invasive technology.

PMID- 23131385
TI  - Controlled biomineralization of electrospun poly(epsilon-caprolactone) fibers to
      enhance their mechanical properties.
AB  - Electrospun polymeric fibers have been investigated as scaffolding materials for
      bone tissue engineering. However, their mechanical properties, and in particular
      stiffness and ultimate tensile strength, cannot match those of natural bones. The
      objective of the study was to develop novel composite nanofiber scaffolds by
      attaching minerals to polymeric fibers using an adhesive material - the mussel
      inspired protein polydopamine - as a "superglue". Herein, we report for the first
      time the use of dopamine to regulate mineralization of electrospun poly(epsilon
      caprolactone) (PCL) fibers to enhance their mechanical properties. We examined
      the mineralization of the PCL fibers by adjusting the concentration of HCO(3)(-)
      and dopamine in the mineralized solution, the reaction time and the surface
      composition of the fibers. We also examined mineralization on the surface of
      polydopamine-coated PCL fibers. We demonstrated the control of morphology, grain
      size and thickness of minerals deposited on the surface of electrospun fibers.
      The obtained mineral coatings render electrospun fibers with much higher
      stiffness, ultimate tensile strength and toughness, which could be closer to the
      mechanical properties of natural bone. Such great enhancement of mechanical
      properties for electrospun fibers through mussel protein-mediated mineralization
      has not been seen previously. This study could also be extended to the
      fabrication of other composite materials to better bridge the interfaces between
      organic and inorganic phases.

PMID- 23131386
TI  - Combined microfabrication and electrospinning to produce 3-D architectures for
      corneal repair.
AB  - Corneal stem cell niches are located within the limbus of the eye and are
      believed to play an important role in corneal regeneration. These niches are
      often lost in corneal disease or trauma. Our work explores the design of
      artificial limbal stem cell niches by the fabrication of biodegradable
      electrospun rings containing bespoke microfeatures. In creating artificial
      niches, we seek to provide a physically protective environment for limbal cells
      to act as a cell reservoir for tissue regeneration purposes. This study describes
      the first step in this challenge to produce structures which structurally
      approximate to the limbal niches. This was achieved using a combination of
      electrospinning and microfabrication. Initial microfabricated structures were
      developed using microstereolithography via a layer-by-layer photocuring approach
      based on the patterning of photocurable polymers, in this case polyethylene
      glycol diacrylate. This was then used as a template on which to electrospin a
      biodegradable membrane of poly(lactic-co-glycolic acid) 50:50, which incorporates
      the features of the underlying microfabricated structures. The study describes
      preliminary evaluation of these constructs using rabbit limbal epithelial and
      stromal cells.

PMID- 23131387
TI  - Fe-Pd based ferromagnetic shape memory actuators for medical applications:
      Biocompatibility, effect of surface roughness and protein coatings.
AB  - Ferromagnetic shape memory (FMSM) alloys constitute an exciting new class of
      smart materials that can yield magnetically switchable strains of several percent
      at constant temperatures and frequencies from quasi-static up to some kilohertz.
      In addition to their FMSM properties, these alloys can still be operated as
      conventional shape memory materials and also exhibit related superelasticity,
      which are both important features for use in medical devices. In this study,
      extensive in vitro assessments demonstrate for the first time that vapor
      deposited single crystalline Fe(70)Pd(30) thin films and roughness graded
      polycrystalline splats of the same stoichiometry exhibit excellent
      biocompatibility and even bioactivity in contact with different cell types-a
      prerequisite for medical applications. The present study shows that fibroblast
      and epithelial cell lines, as well as primary osteoblast cells, proliferate well
      on Fe-Pd. The number of focal contacts, important for strong tissue bonding, can
      be improved with different binding agents from the extracellular matrix. However,
      even without coating, there is clear evidence that cells on Fe-Pd substrates
      behave similarly to control experiments. Additionally, cytotoxic effects of
      polycrystalline surfaces with various roughness profiles can be excluded, giving
      another tunable parameter for applying Fe-Pd magnetically switchable membranes
      in, e.g., stents and valves.

PMID- 23131388
TI  - Early development of the metabolic syndrome after chemotherapy for testicular
      cancer.
AB  - BACKGROUND: The metabolic syndrome (MS) might increase the risk of cardiovascular
      disease in testicular cancer (TC) survivors. We investigated its prevalence,
      development, vascular implications, and the role of gonadal function. METHODS: TC
      survivors treated with chemotherapy and follow-up >=3 years (N = 370, study I)
      were retrospectively evaluated for the development of cardiovascular risk
      factors. A subgroup followed 3-20 years (N = 173, study II) was compared with
      controls (N = 1085) for MS prevalence and evaluated for vascular function.
      RESULTS: In TC survivors (study I), 24% developed overweight, 24%
      hypercholesterolemia, and 30% hypertension, after median follow-up of 1.7, 0.9,
      and 5.1 years, respectively. At the median follow-up of 5 years (study II), 25%
      of survivors have the MS {odds ratio (OR) 2.2, [95% confidence interval (CI) 1.5
      3.3] compared with controls}. Survivors with MS have features of inflammation and
      prothrombotic state, increased carotid artery intima-media thickness. Survivors
      with testosterone levels <15 nmol/l (22%) have an increased risk of the MS (OR
      4.1, 95% CI 1.8-9.3). CONCLUSIONS: The current data suggest that the MS occurs at
      earlier age in TC survivors treated with chemotherapy compared with controls and
      is accompanied by early signs of atherosclerosis. As low testosterone may have a
      causal role, it is a target for interventions.

PMID- 23131389
TI  - From targets to targeted therapies and molecular profiling in non-small cell lung
      carcinoma.
AB  - Although tumor molecular-profile-directed therapy appears promising in early
      clinical studies, there are many practical challenges to its successful clinical
      application in non-small-cell lung cancer (NSCLC). These challenges may be
      broadly classified as those relating to tumor (heterogeneity), tissue
      (acquisition and processing), testing (assays for molecular profiling) and trials
      (clinical evaluation of molecular markers and drugs). Strategies to overcome
      these challenges include (i) understanding the biological basis of tumor
      heterogeneity and of carcinogenesis in the large subset of patients with no
      currently evident driver events; (ii) technological advances in minimally
      invasive acquisition of tumor and next-generation sequencing (NGS) which would
      enable single-platform analysis of molecular alterations in limited tissue at a
      reasonable turnaround time (TAT); (iii) deliberation in early stages of drug
      development as well as clinical trial design to identify, validate and assess the
      clinical utility of biomarkers in conjunction with drugs and (iv) collaboration
      to improve understanding of and accrual to trials enrolling patients with rare
      molecular alterations.

PMID- 23131390
TI  - A clinical-biological risk stratification model for resected gastric cancer:
      prognostic impact of Her2, Fhit, and APC expression status.
AB  - BACKGROUND: To obtain a prognostic stratification model for resected gastric
      cancer patients. PATIENTS AND METHODS: Clinicopathological and molecular data
      (expression of Cdx2, Apc, beta-catenin, E-cadherin, Fhit, p53, and human
      epidermal growth factor receptor-2 (Her2); HER2 and TOPO2A gene copy number;
      PIK3CA mutations; microsatellite instability) were correlated to cancer
      specific/overall survival (CSS/OS) using a Cox model. Individual patient
      probability (IPP) was estimated by logistic equation. A continuous score to
      identify risk-classes was derived according to the model ratios. RESULTS: Two
      hundred eight patients were studied (median follow-up 20 months). At multivariate
      analysis, sex, stage, margins, location, nodes, Apc, and Fhit were independent
      predictors for CSS; the same factors (and age and Her2, except Fhit) predicted
      OS. Multivariate model predicted IPP with high prognostic accuracy (0.90 for CSS;
      0.91 for OS). A two-class model significantly separated low- and high-risk
      patients for CSS (23.4% and 85.6%, P < 0.0001) and OS (21.4% and 82.0%, P <
      0.0001). A three-class model differentiated low-, intermediate-, and high-risk
      patients for CSS (6.3%, 35.3%, and 88.0%, P < 0.0001) and OS (6.1%, 34.6%, and
      86.5%, P < 0.0001). CONCLUSIONS: A risk classification system comprising the
      immunohistochemical expression of three proteins (Apc, Fhit, and Her2) and five
      clinicopathological parameters (stage, resected nodes, margins, location, and
      sex) accurately separates the resected gastric cancer patients into three classes
      of risk.

PMID- 23131391
TI  - RNA-based determination of ESR1 and HER2 expression and response to neoadjuvant
      chemotherapy.
AB  - BACKGROUND: Hormone and human epidermal growth factor receptor 2 (HER2) receptors
      are the most important breast cancer biomarkers, and additional objective and
      quantitative test methods such as messenger RNA (mRNA)-based quantitative
      analysis are urgently needed. In this study, we investigated the clinical
      validity of RT-PCR-based evaluation of estrogen receptor (ESR1) and HER2 mRNA
      expression. PATIENTS AND METHODS: A total of 1050 core biopsies from two
      retrospective (GeparTrio, GeparQuattro) and one prospective (PREDICT) neoadjuvant
      studies were evaluated by quantitative RT-PCR for ESR1 and HER2. RESULTS: ESR1
      mRNA was significantly predictive for reduced response to neoadjuvant
      chemotherapy in univariate and multivariate analysis in all three cohorts. The
      complete pathologically documented response (pathological complete response, pCR)
      rate for ESR1+/HER2- tumors was 7.3%, 8.0% and 8.6%; for ESR1-/HER2- tumors it
      was 34.4%, 33.7% and 37.3% in GeparTrio, GeparQuattro and PREDICT, respectively
      (P < 0.001 in each cohort). In the Kaplan-Meier analysis in GeparTrio patients
      with ESR1+/HER2- tumors had the best prognosis, compared with ESR1-/HER2- and
      ESR1-/HER2+ tumors [disease-free survival (DFS): P < 0.0005, overall survival
      (OS): P < 0.0005]. CONCLUSIONS: Our results suggest that mRNA levels of ESR1 and
      HER2 predict response to neoadjuvant chemotherapy and are significantly
      associated with long-term outcome. As an additional option to standard
      immunohistochemistry and gene-array-based analysis, quantitative RT-PCR analysis
      might be useful for determination of the receptor status in breast cancer.

PMID- 23131392
TI  - Osteosarcomas of the mandible: multidisciplinary management of a rare tumor of
      the young adult a cooperative study of the GSF-GETO, Rare Cancer Network,
      GETTEC/REFCOR and SFCE.
AB  - BACKGROUND: Mandibular osteosarcomas (MOS) mostly affect young adults. Their
      treatment is extrapolated from that of extragnathic osteosarcomas. MATERIAL AND
      METHODS: A retrospective multicooperative group study was conducted to determine
      the impact of chemotherapy, adjuvant radiation therapy and surgery on outcomes
      and to identify prognostic factors. This ethical committee-approved study
      included a centralized review of histology slides and operative reports. RESULTS:
      Of 111 patients, 58.6% were male, median age 35 years (13%, <=18 years).
      Histology was osteoblastic, chondroblastic, fibroblastic, conventional not
      otherwise specified and others in 39.6%, 30.6%, 8.1%, 12.6% and 8.0%,
      respectively. Pathological World Health Organisation grades were low,
      intermediate and high grade in 6.4%, 11.8% and 81.8%, respectively. Surgery was
      carried out for 94.5% of patients. Neoadjuvant chemotherapy (mixed protocols) was
      carried out in 93.1% of patients. Postoperative chemotherapy and radiotherapy
      were carried out in 54.7% and 23.8%, respectively. Median follow-up was 59.6
      months (range). Five-year local control, metastasis-free, disease-free and
      overall survival rates were 64.6%, 68.9%, 53.2% and 69.2%, respectively. Survival
      was significantly associated with age, tumor size and surgery. Wide surgery with
      clear margins and free flap reconstruction was the strongest prognostic factor.
      Neoadjuvant chemotherapy improved disease-free and metastatic-free survival and
      increased clear margins rates from 50% to 68%. Intermediate grades behaved like
      high grades in terms of metastatic-free and disease-free survival. CONCLUSION:
      This homogeneous series is the largest to date and emphasizes the major impact of
      clear margins and multidisciplinary management. Neoadjuvant chemotherapy improves
      disease-free survival and should be recommended for both high and intermediate
      grade MOS.

PMID- 23131393
TI  - Diagnostic value of immunohistochemistry for the detection of the BRAFV600E
      mutation in primary lung adenocarcinoma Caucasian patients.
AB  - BACKGROUND: Non-small-cell lung carcinoma (NSCLC) patients with a BRAF(V600E)
      mutation benefit from targeted therapy. The usefulness of immunohistochemistry
      (IHC) as an alternative approach for the detection of BRAF(V600E) in NSCLC
      patients has not been evaluated until now. This study compared the specificity
      and sensitivity of IHC with other methods for the detection of BRAF(V600E) in
      primary lung adenocarcinoma. PATIENTS AND METHODS: BRAF mutations were analysed
      by DNA sequencing of a Caucasian subpopulation of selected 450 of 1509 (30%)
      EGFR, KRAS, PI3KA, Her2 and EML4-ALK wild-type (wt) primary lung adenocarcinomas.
      Detection of the BRAF(V600E) mutation was carried out by IHC using the VE1 clone
      antibody and compared with the results of other molecular methodologies. RESULTS:
      Of 450 (9%) of tumours, 40 harboured a BRAF mutation, which corresponded to
      either a BRAF(V600E) or a non-BRAF(V600E) mutation in 21 of 450 (5%) and 19 of
      450 (4%) cases, respectively. The IHC VE1 assay was positive in 19 of 21 (90%)
      BRAF(V600E)-mutated tumours and negative in all BRAF(nonV600E)-mutated tumours.
      CONCLUSION: IHC using the VE1 clone is a specific and sensitive method for the
      detection of BRAF(V600E) and may be an alternative to molecular biology for the
      detection of mutations in NSCLC.

PMID- 23131394
TI  - Local thrombolysis for patients of severe cerebral venous sinus thrombosis during
      puerperium.
AB  - OBJECTIVE: To explore and evaluate the efficacy of intrasinus thrombolysis (IST)
      in patients with cerebral venous sinus thrombosis (CVST) during postpartum
      period. METHODS: 11 patients during postpartum period with CVST who received IST
      during July 2007-November 2011 were included. Urokinase was infused into the
      sinuses via a microcatheter. Magnetic resonance venography (MRV) was performed to
      assess the recanalization of venous sinuses. RESULTS: Before discharge, the
      intracranial pressure in 11 patients was under 200 mmH(2)O. MRV confirmed that
      venous sinus of 9 patients were smooth. The cortex venous and deep venous
      recovered to normal. Venous sinus of 2 patients recanalized partly, and cortex
      venous and deep venous had compensation. 9 patients had good outcome and 2
      patients had only mild deficits. CONCLUSION: Intrasinus thrombolysis is safe and
      effective in patients with severe cerebral venous sinus thrombosis during
      postpartum period.

PMID- 23131395
TI  - US screening for detection of nonpalpable locoregional recurrence after
      mastectomy.
AB  - PURPOSE: To assess the value of screening ultrasonography (US) in the detection
      of nonpalpable locoregional recurrence following mastectomy for breast cancer and
      to describe the US appearances of occult recurrent cancers. MATERIALS AND
      METHODS: During a 36-month period, 1180 consecutive US screenings were performed
      for mastectomy sites and ipsilateral axillary fossae in 468 asymptomatic women
      who had undergone mastectomy for breast cancer. All US results were divided into
      three groups: negative findings, probably benign nodules, and suspicious for
      malignant nodules. The final diagnoses were based on pathology results and
      clinical or sonographic follow-up for more than 12 months. The diagnostic
      performance of US for detecting nonpalpable locoregional recurrence was assessed.
      The US appearances of occult recurrent cancers were retrospectively reviewed.
      RESULTS: Of the 468 patients assessed, 19 (4.1%) showed "suspicious for malignant
      nodules"; of these lesions, 10 were malignant. One false-negative case was
      identified. The sensitivity and specificity were 90.9% and 98.0%, respectively. A
      biopsy positive predictive value of 52.6% was observed. Cancer detection rates
      were 2.1% with US screenings of mastectomy sites and ipsilateral axillary fossae.
      The common US features of occult recurrences at the mastectomy sites were
      irregular shaped, not-circumscribed marginated, and hypoechoic masses with
      intratumoral vascularities. The most common location was within the deep muscle
      layer. CONCLUSION: Although locoregional recurrence infrequently occurs after
      mastectomy for breast cancer, screening US enables detection of nonpalpable
      cancer before it can be detected by clinical examination. Routine follow-up US
      can be advocated for early detection of nonpalpable locoregional recurrent
      cancer.

PMID- 23131396
TI  - Effects of inorganic nutrients in recycled water on freshwater phytoplankton
      biomass and composition.
AB  - Planned indirect potable reuse water treated with advanced wastewater
      technologies (AWWT) to remove pollutants is increasingly being used to augment
      drinking water and groundwater supplies. While the treatment process
      substantially reduces the high nitrogen (N) and phosphorus (P) concentrations
      typically of wastewater, both nutrients can remain at concentrations and in
      biologically available forms that may stimulate phytoplankton growth in nutrient
      deficient systems. This study examined the short-term effect of N plus P
      additions, at a range of concentrations, on phytoplankton growth and species
      composition in mesocosm experiments in a subtropical reservoir. Nitrate (NO(3))
      plus orthophosphate (PO(4)) concentrations as low as 50 and 5 MUg L(-1),
      respectively, resulted in significant increases in phytoplankton biomass, with a
      3.99 MUg L(-1) increase in chlorophyll a concentration with every 10 MUg L(-1)
      increase in N plus 1 MUg L(-1) in P. The system was likely to be co-limited
      because the addition of N or P alone did not result in increased chlorophyll a
      concentrations compared with the control. However, the toxic cyanobacterium,
      Cylindrospermopsis raciborskii, had higher growth rates with P addition alone.
      This study has shown that inputs of AWWT water have the potential to increase the
      phytoplankton biomass in this subtropical reservoir, at least in the short term.
      Therefore, the effect of AWWT water on water quality in reservoirs should be
      further investigated before widespread application occurs.

PMID- 23131398
TI  - Physician Responsibilities in a World of CAM.

PMID- 23131397
TI  - Trends in Canadian hospital standardised mortality ratios and palliative care
      coding 2004-2010: a retrospective database analysis.
AB  - BACKGROUND: The hospital standardised mortality ratio (HSMR), anchored at an
      average score of 100, is a controversial macromeasure of hospital quality. The
      measure may be dependent on differences in patient coding, particularly since
      cases labelled as palliative are typically excluded. OBJECTIVE: To determine
      whether palliative coding in Canada has changed since the 2007 national
      introduction of publicly released HSMRs, and how such changes may have affected
      results. DESIGN: Retrospective database analysis. SETTING: Inpatients in Canadian
      hospitals from April 2004 to March 2010. PATIENTS: 12 593 329 hospital discharges
      recorded in the Canadian Institute for Health Information (CIHI) Discharge
      Abstract Database from April 2004 to March 2010. MEASUREMENTS: Crude mortality
      and palliative care coding rates. HSMRs calculated with the same methodology as
      CIHI. A derived hospital standardised palliative ratio (HSPR) adjusted to a
      baseline average of 100 in 2004-2005. Recalculated HSMRs that included palliative
      cases under varying scenarios. RESULTS: Crude mortality and palliative care
      coding rates have been increasing over time (p<0.001), in keeping with the
      nation's advancing overall morbidity. HSMRs in 2008-2010 were significantly lower
      than in 2004-2006 by 8.55 points (p<0.001). The corresponding HSPR rises
      dramatically between these two time periods by 48.83 points (p<0.001). Under
      various HSMR scenarios that included palliative cases, the HSMR would have at
      most decreased by 6.35 points, and may have even increased slightly. LIMITATIONS:
      Inability to calculate a definitively comparable HSMR that include palliative
      cases and to account for closely timed changes in national palliative care coding
      guidelines. CONCLUSIONS: Palliative coding rates in Canadian hospitals have
      increased dramatically since the public release of HSMR results. This change may
      have partially contributed to the observed national decline in HSMR.

PMID- 23131399
TI  - When Patients Choose CAM over EBM-How to Negotiate Treatment.

PMID- 23131400
TI  - "CAM" Education in Medical Schools-A Critical Opportunity Missed.

PMID- 23131402
TI  - AMA Code of Medical Ethics' Opinions on Ethical Referral.

PMID- 23131401
TI  - Herbal supplements as placebos.

PMID- 23131403
TI  - Fairness in the Context of CAM.

PMID- 23131404
TI  - The lipid-lowering properties of red yeast rice.

PMID- 23131405
TI  - Choosing alternative treatments for children.

PMID- 23131406
TI  - Licensure of complementary and alternative practitioners.

PMID- 23131407
TI  - Integrative medicine and cancer care.

PMID- 23131408
TI  - Chiropractic's Fight for Survival.

PMID- 23131410
TI  - Medicine's Great Divide-The View from the Alternative Side.

PMID- 23131409
TI  - Resisting the Understandable Appeal of CAM.

PMID- 23131411
TI  - About the contributors.

PMID- 23131412
TI  - Purpuroines A-J, halogenated alkaloids from the sponge Iotrochota purpurea with
      antibiotic activity and regulation of tyrosine kinases.
AB  - Ten new halogenated alkaloids named purpuroines A-J (1-10), and a known analogue
      (11), were isolated from the marine sponge Iotrochota purpurea. Their structures
      were elucidated by extensive spectroscopic (IR, MS, 1D and 2D NMR) data analyses.
      The inhibitory activity of some compounds against a panel of human disease
      related fungi and bacteria are evaluated. Bioassay for the regulation of tyrosine
      kinases revealed compounds 1 and 4 possessing selective inhibition against the
      kinase LCK. Primary structure-activity relationship is discussed.

PMID- 23131413
TI  - Mannich bases of scutellarein as thrombin-inhibitors: design, synthesis,
      biological activity and solubility.
AB  - Two series of 8-aminomethylated derivatives were prepared by Mannich reaction of
      scutellarein (2) with appropriate aliphatic amines, alicyclic amines and
      formaldehyde. All the compounds were tested for their thrombin inhibition
      activity through the analyzation of prothrombin time (PT), activated partial
      thromboplastin time (APTT), thrombin time (TT) and fibrinogen (FIB). The
      antioxidant activities of these target products were assessed by 1,1-diphenyl-2
      picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH)
      assay using 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT)
      assay method and the solubility were assessed by ultraviolet (UV). The results
      showed that morpholinyl aminomethylene substituent derivative (3d) demonstrated
      stronger anticoagulant activity, better water solubility and good antioxidant
      activity compared with scutellarein (2), which warrants further development as a
      agent for ischemic cerebrovascular disease treatment.

PMID- 23131414
TI  - Synergistic effects of BDNF and rehabilitative training on recovery after
      cervical spinal cord injury.
AB  - Promoting the rewiring of lesioned motor tracts following a spinal cord injury is
      a promising strategy to restore motor function. For instance, axonal collaterals
      may connect to spared, lesion-bridging neurons, thereby establishing a detour for
      descending signals and thus promoting functional recovery. In our rat model of
      cervical spinal cord injury, we attempted to promote targeted rewiring of the
      unilaterally injured corticospinal tract (CST) via the spared reticulospinal
      tract (RtST). To promote new connections between the two tracts in the brainstem,
      we administered viral vectors producing two neurotrophins. Brain-derived
      neurotrophic factor (BDNF), a known promotor of collateral growth, was expressed
      in the motor cortex, and neurotrophin 3 (NT-3), which has chemoattractive
      properties, was expressed in the reticular formation. Because rehabilitative
      training has proven to be beneficial in promoting functionally meaningful
      plasticity following injury, we added training in a skilled reaching task.
      Different neurotrophin or control treatments with or without training were
      evaluated. As hypothesized, improvements of motor performance with the injured
      forelimb following neurotrophin treatment alone were absent or modest compared to
      untreated controls. In contrast, we found a significant synergistic effect on
      performance when BDNF treatment was combined with training. The mechanism of this
      recovery remains unidentified, as histological analyses of CST and RtST
      collateral projections did not reveal differences among treatment groups. In
      conclusion, we demonstrate that following a cervical spinal lesion,
      rehabilitative training is necessary to translate effects of BDNF into functional
      recovery by mechanisms which are likely independent of collateral sprouting of
      the CST or RtST into the gray matter.

PMID- 23131415
TI  - Complete response of metastatic cutaneous squamous cell carcinoma to cetuximab
      plus paclitaxel.
AB  - BACKGROUND AND METHODS: Cetuximab therapy results strongly active in advanced
      cutaneous squamous cell carcinoma (cSCC). A patient affected by a rapidly
      progressing, already irradiated and cisplatin-refractory cSCC, with lung, pleura
      and thoracic lymph nodes metastasis, was treated with weekly cetuximab and
      paclitaxel. RESULTS: Treatment was well tolerated and a partial response was
      obtained after four months of cetuximab plus paclitaxel therapy. Then we
      continued maintenance cetuximab for another seven months with tumor shrinkage
      until complete response, maintained after six months. CONCLUSIONS: Cetuximab was
      safely associated with paclitaxel, obtaining a rapid tumor response in cisplatin
      refractory metastatic cSCC. Single-agent cetuximab maintenance sustained tumor
      shrinkage until complete response.

PMID- 23131416
TI  - More than a marine propeller--the flagellum of the probiotic Escherichia coli
      strain Nissle 1917 is the major adhesin mediating binding to human mucus.
AB  - The flagellum of the probiotic Escherichia coli strain Nissle 1917 (EcN) is not
      just responsible for motility, but also for EcN's ability to induce the
      production of human beta-defensin 2. Here, we report a third function of this EcN
      organell. In this study we investigated the role of the EcN flagellum in adhesion
      to different host tissues by ex vivo and in vitro studies. Ex vivo studies with
      cryosections of human gut biopsies revealed that the flagellum of EcN is most
      likely important for efficient adhesion to the human intestinal tract. These
      results and in vitro studies with different epithelial cells indicated that the
      presence of mucus is important for efficient mediation of adhesion by the
      flagellum of EcN. We observed direct interaction between isolated flagella from
      EcN wild type and porcine mucin 2 as well as human mucus. However, we could not
      observe any interaction of the flagella with murine mucus. For the first time, we
      identified the mucus component gluconate as one receptor for the binding of
      flagella from EcN and were able to exclude the flagellin domain D3 as a
      responsible interaction partner. We propose that the flagellum of EcN is its
      major adhesin in vivo, which enables this probiotic strain to compete efficiently
      for binding sites on host tissue with several bacterial pathogens.

PMID- 23131417
TI  - Sources of patient uncertainty when reviewing medical disclosure and consent
      documentation.
AB  - OBJECTIVES: Despite evidence that medical disclosure and consent forms are
      ineffective at communicating the risks and hazards of treatment and diagnostic
      procedures, little is known about exactly why they are difficult for patients to
      understand. The objective of this research was to examine what features of the
      forms increase people's uncertainty. METHODS: Interviews were conducted with 254
      individuals. After reading a sample consent form, participants described what
      they found confusing in the document. With uncertainty management as a
      theoretical framework, interview responses were analyzed for prominent themes.
      RESULTS: Four distinct sources of uncertainty emerged from participants'
      responses: (a) language, (b) risks and hazards, (c) the nature of the procedure,
      and (d) document composition and format. CONCLUSIONS: Findings indicate the value
      of simplifying medico-legal jargon, signposting definitions of terms, removing
      language that addresses multiple readers simultaneously, reorganizing bulleted
      lists of risks, and adding section breaks or negative space. PRACTICE
      IMPLICATIONS: These findings offer suggestions for providing more straightforward
      details about risks and hazards to patients, not necessarily through greater
      amounts of information but rather through more clear and sufficient material and
      better formatting.

PMID- 23131418
TI  - Software applications for flux balance analysis.
AB  - Flux balance analysis (FBA) is a widely used computational method for
      characterizing and engineering intrinsic cellular metabolism. The increasing
      number of its successful applications and growing popularity are possibly
      attributable to the availability of specific software tools for FBA. Each tool
      has its unique features and limitations with respect to operational environment,
      user-interface and supported analysis algorithms. Presented herein is an in-depth
      evaluation of currently available FBA applications, focusing mainly on usability,
      functionality, graphical representation and inter-operability. Overall, most of
      the applications are able to perform basic features of model creation and FBA
      simulation. COBRA toolbox, OptFlux and FASIMU are versatile to support advanced
      in silico algorithms to identify environmental and genetic targets for strain
      design. SurreyFBA, WEbcoli, Acorn, FAME, GEMSiRV and MetaFluxNet are the distinct
      tools which provide the user friendly interfaces in model handling. In terms of
      software architecture, FBA-SimVis and OptFlux have the flexible environments as
      they enable the plug-in/add-on feature to aid prospective functional extensions.
      Notably, an increasing trend towards the implementation of more tailored e
      services such as central model repository and assistance to collaborative efforts
      was observed among the web-based applications with the help of advanced web
      technologies. Furthermore, most recent applications such as the Model SEED, FAME,
      MetaFlux and MicrobesFlux have even included several routines to facilitate the
      reconstruction of genome-scale metabolic models. Finally, a brief discussion on
      the future directions of FBA applications was made for the benefit of potential
      tool developers. 

PMID- 23131419
TI  - Embryos without secrets: an expert panel study on comprehensive embryo testing
      and the responsibility of the clinician.
AB  - The introduction of comprehensive testing techniques, such as microarray
      technology or whole genome sequencing, in embryo testing has the potential to
      change the practice of Preimplantation Genetic Diagnosis (PGD) and
      Preimplantation Genetic Screening (PGS). However, the extra information these
      procedures yield may potentially generate dilemmas for couples and professionals
      regarding the scope of the tests and the selection of the right embryo. In order
      to understand this complexity and reflect on its consequences, we organized two
      expert panels consisting of professionals working in the field of assisted
      reproduction and/or genetics. We found that there is great uncertainty amongst
      professionals how to tackle questions related to comprehensive screening, such as
      which conditions to test for and who should have the final say on which embryo to
      select, and a lack of a framework from which such questions can be answered.
      Moreover, the complexity of genetic information comprehensive tests may yield may
      make it impossible to select the best embryo altogether.

PMID- 23131420
TI  - Photocatalytic degradation of microcystin-LR in aqueous solutions.
AB  - In this work, the photocatalytic degradation of aqueous microcystin-LR was
      studied using TiO(2) and ZnO as photocatalysts. The process was optimised and
      characterised at the bench scale (200 mL); both semiconductors exhibited a high
      degradation capacity at reaction times of 1 min (degradation greater than 95%).
      The transient species that were observed indicate that the degradation occurs via
      the multiple hydroxylation and elimination of the labile peptide residues of the
      molecule. When photocatalysis was applied in a continuous treatment system (20-50
      L), the photocatalytic process exhibited a high degradation efficiency, which
      resulted in residual microcystin-LR concentrations that were less than 1 MUg L(
      1) (C(0)=5 MUg L(-1)).

PMID- 23131421
TI  - Effect of varying glucose and glucosamine concentration in vitro on mouse oocyte
      maturation and developmental competence.
AB  - The effects of hyper- and hypo-glycaemic conditions during the in vitro
      maturation of mouse cumulus-oocyte complexes on developmental competence were
      examined, with an emphasis on the role of the hexosamine biosynthesis pathway. A
      low (1 mM) glucose concentration achieved optimal oocyte competence (3-fold
      higher blastocyst development rate compared with high (30 mM) glucose, P<0.05).
      In addition, glucose supplementation during only the first hour after release
      from the follicle was necessary and sufficient to support oocyte maturation and
      embryo development to the blastocyst stage. Glucosamine (a known hyperglycaemic
      mimetic and specific activator of the hexosamine pathway) was able to substitute
      for glucose during this first hour, indicating that flux through the hexosamine
      pathway is essential for oocyte competence. In the absence of glucose throughout
      the maturation period, glucosamine was not able to increase developmental
      competence, and at higher concentrations (2.5 and 5 mM) had a detrimental effect
      on MII and blastocyst development rates, compared with controls (P<0.05). These
      experiments underscore the importance of glucose metabolic pathways during in
      vitro maturation and support the concept that excess flux through the hexosamine
      pathway has detrimental consequences.

PMID- 23131422
TI  - Elevated serum MMP-9/TIMP-1 ratio in patients with homozygous familial
      hypercholesterolemia: effects of LDL-apheresis.
AB  - OBJECTIVE: Matrix degradation within an atherosclerotic plaque is an important
      pathogenic factor in atherosclerosis, and is largely modulated by the balance
      between matrix metalloproteinases (MMPs) and their endogenous inhibitors (i.e.,
      tissue inhibitor of MMPs [TIMPs]). Familial hypercholesterolemia (FH) is a rare
      inherited disorder associated with premature coronary heart disease. The aim of
      the present study was to examine MMP-9 and TIMP-1 on plasma and cellular mRNA
      levels in homozygous FH patients (n=7) compared with age- and sex-matched
      heterozygous FH patients (n=6), and with healthy subjects (n=7), and to test
      whether once-weekly LDL-apheresis (three consecutive sessions) of homozygous FH
      patients show short-term effects on these variables. RESULTS: The main findings
      were that (i) Compared to healthy control subjects, homozygous FH patients have
      significantly higher serum levels of MMP-9 and lower levels of TIMP-1, and
      consequently significantly higher MMP-9/TIMP-1 ratio, potentially reflecting
      higher MMP-9 activity. (ii) Peripheral blood mononuclear cells (PBMC) isolated
      from FH homozygotes have significantly higher mRNA levels of MMP-9 compared to
      cells from heterozygotes. (iii) TNFalpha-stimulated PBMC from FH homozygotes
      released borderline-significantly more MMP-9 than cells from heterozygotes and
      healthy controls. (iv) LDL-apheresis (one day before treatment versus fifteen
      days later, on the day after the weekly treatment) had no significant short-term
      effect on any of the MMP-9 and TIMP-1 variables measured in serum and cells.
      CONCLUSIONS: The data may suggest that homozygous FH patients have an enhanced
      matrix degrading potential as compared with heterozygous FH patients and healthy
      controls, potentially contributing to the increased cardiovascular risk observed
      in these patients.

PMID- 23131423
TI  - Interleukin-17A genetic variants can confer resistance to brucellosis in Iranian
      population.
AB  - On the subject of brucellosis, it seems that Th1/Th2 cytokines balance may be
      involved in the resistance or susceptibility to Brucella infection. In this
      respect, Th1 cytokines confer resistance, while Th2 cytokines predispose
      brucellosis. It is also clarified that IL-17 is required for the induction of IFN
      gamma and IL-12 in macrophages and dendritic cells. Then, it seems that IL-17 can
      affect the induction of Th1 immunity which is necessary for controlling Brucella.
      In the present study, we tried to investigate probable relationship between IL
      17A genetic variants and susceptibility to the human brucellosis. One hundred and
      seventy six patients with brucellosis and 84 healthy animal husbandmen, who
      consumed contaminated raw milk and dairy products from animals with brucellosis,
      were included in this study. All individuals were genotyped for 9 single
      nucleotide polymorphisms (SNPs) (rs4711998AG, rs8193036CT, rs3819024AG,
      rs2275913AG, rs3819025AG, rs8193038AG, rs3804513AT, rs1974226AG and rs3748067AG)
      being selected by using NCBI SNP database and literature using polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) method. The
      distribution of IL-17 rs4711998, rs8193038, rs3748067 AA genotypes and AAGAA
      haplotype were significantly more frequent in the patients than in the controls
      (P=0.008, 0.0019, 0.003 and 0.002, respectively) while IL-17 genotypes
      rs3819024GG and rs3819025AA were more frequent in the controls than the patients
      (P=0.001 and 0.0035, respectively). Based on the results, IL-17 rs4711998,
      rs8193038, rs3748067 AA genotypes and AAGAA haplotype could be considered as
      susceptibility factors for brucellosis while the inheritance of IL-17 rs3819024GG
      and rs3819025AA genotypes might be resistance factors against the disease.

PMID- 23131424
TI  - Sulfadoxine-pyrimethamine resistance in Plasmodium falciparum: a zoomed image at
      the molecular level within a geographic context.
AB  - Antimalarial chemotherapy is one of the main pillars in the prevention and
      control of malaria. Following widespread resistance of Plasmodium falciparum to
      chloroquine, sulfadoxine-pyrimethamine came to the scene as an alternative to the
      cheap and well-tolerated chloroquine. However, widespread resistance to
      sulfadoxine-pyrimethamine has been documented. In vivo efficacy tests are the
      gold standard for assessing drug resistance and treatment failure. However, they
      have many disadvantages, such as influence of host immunity and drug
      pharmacokinetics. In vitro tests of antimalarial drug efficacy also have many
      technical difficulties. Molecular markers of resistance have emerged as
      epidemiologic tools to investigate antimalarial drug resistance even before
      becoming clinically evident. Mutations in P. falciparum dihydrofolate reductase
      and dihydrofolate synthase have been extensively studied as molecular markers for
      resistance to pyrimethamine and sulfadoxine, respectively. This review highlights
      the resistance of P. falciparum at the molecular level presenting both supporting
      and opposing studies on the utility of molecular markers.

PMID- 23131425
TI  - Age-related changes of aquaporin expression patterns in the postnatal rat retina.
AB  - Previous studies revealed that the rat retina contains numerous membrane-located
      water channels, the aquaporins (AQPs). Protein expression patterns of AQP1-4, 6
      and 9 were examined by immunohistochemistry. In the present study, we
      investigated the immunolocalization of AQP1-4, 6 and 9 during postnatal
      development in the rat retina and examined the effect of age on the tissue
      distribution of these channels. AQP1, 3, 4, 6 and 9 showed gradually increased
      expression in rat retinas from postnatal week 1 to week 12, and decreased in the
      40-week-old rat retinas. AQP2 expression was barely seen in the first week in rat
      retinas and displayed a significant increase from week 1 to week 4, however no
      significant alteration of AQP2 was observed after 4weeks of development. AQP1 and
      4 immunoreactivities were present in the inner limiting membrane (ILM), the
      ganglion cell layer (GCL), inner nuclear layer (INL) and retinal pigment
      epithelium (RPE) in the 4-, 12- and 40-week-old rat retinas. The RPE, OLM and ILM
      showed a remarkable expression of AQP1-4, 6 and 9 in the 4, 12 and 40-week-old
      rat retinas. The reduced expression of AQPs in aged rat retinas may indicate the
      involvement of AQPs in the pathogenesis of age-related retinal diseases.

PMID- 23131426
TI  - Zonal distribution of perforant path cells in layer III of the entorhinal area
      projecting to CA1 and subiculum in the rat.
AB  - The distribution pattern of the cells that give rise to perforant path
      projections, including direct entorhino-CA1 and entorhino-subicular projections,
      was investigated in layer III of the medial and lateral entorhinal areas in the
      rat using retrograde labeling with horseradish peroxidase conjugated to wheat
      germ agglutinin and cholera toxin B subunit. Using two-dimensional unfolded maps
      of the entire hippocampal and parahippocampal fields, we found that cells
      projecting to a certain septotemporal level of CA1 and the subiculum were
      distributed in a band-like zone extending across the medial and lateral
      entorhinal areas. The transverse axis of these zones was disposed parallel to the
      rhinal fissure and their longitudinal axis was perpendicular to the boundary
      between the medial and lateral entorhinal areas. Projections to the septal CA1
      originated from the zone near the rhinal fissure, whereas those to the temporal
      CA1 originated from the zone far from the rhinal fissure. Each zone in both the
      medial and lateral entorhinal areas involved many neurons projecting to a wide
      proximodistal range of CA1 and the subiculum. These results suggest that the
      entorhino-CA1 and entorhino-subicular perforant path projections are generally
      organized in a band-like zonal fashion with a gradient, rather than a point-to
      point topographic arrangement.

PMID- 23131427
TI  - A novel model of combined neuropathic and inflammatory pain displaying long
      lasting allodynia and spontaneous pain-like behaviour.
AB  - Many clinical cases of chronic pain exhibit both neuropathic and inflammatory
      components. In contrast, most animal models of chronic pain focus on one type of
      injury alone. Here we present a novel combined model of both neuropathic and
      inflammatory pain and characterise its distinctive properties. This combined
      model of chronic constriction injury (CCI) and intraplantar Complete Freund's
      Adjuvant (CFA) injection results in enhanced mechanical allodynia, thermal
      hyperalgesia, a static weight bearing deficit, and notably pronounced spontaneous
      foot lifting (SFL) behaviour (which under our conditions was not seen in either
      individual model and may reflect ongoing/spontaneous pain). Dorsal root ganglion
      (DRG) expression of Activating Transcription Factor-3 (ATF-3), a marker of axonal
      injury, was no greater in the combined model than CCI alone. Initial
      pharmacological characterisation of the new model showed that the SFL was
      reversed by gabapentin or diclofenac, typical analgesics for neuropathic or
      inflammatory pain respectively, but not by mexiletine, a Na(+) channel blocker
      effective in both neuropathic and inflammatory pain models. Static weight bearing
      deficit was moderately reduced by gabapentin, whereas only diclofenac reversed
      mechanical allodynia. This novel animal model of chronic pain may prove a useful
      test-bed for further analysing the pharmacological susceptibility of complicated
      clinical pain states.

PMID- 23131428
TI  - Modular hemipelvic endoprosthesis reconstruction--experience in 100 patients with
      mid-term follow-up results.
AB  - INTRODUCTION: Pelvic endoprostheses are becoming more commonly used in recent
      years. In 2007, we reported the early results of modular hemipelvic
      endoprosthesis. In order to provide longer follow-up results, we conducted the
      current study. OBJECTIVE: To explore overall survival, local recurrence rate,
      metastasis rate, function score and survivorship of the prosthesis and related
      complications. METHODS: We retrospectively reviewed one hundred consecutive
      patients who received reconstruction with modular hemipelvic endoprostheses from
      June 2001 to March 2010. The living patients were followed for an average of 52.9
      (range, 24-103) months. There were 85 primary tumors and 15 isolated metastases.
      RESULTS: At the time of last follow-up, fifty-eight patients were alive with no
      evidence of disease and thirty-six patients died of disease. Twenty patients
      experienced a local recurrence and twenty-eight patients developed distant
      metastasis. Patients with wide surgical margins had a significantly lower local
      recurrence rate than those with inadequate margins (p = 0.03). The mean MSTS
      (Musculoskeletal Tumor Society) 93 score was 57.2% (range, 16.7-86.7%). The mean
      Karnofsky Performance Score (KPS) was 64.4 (range, 30-90). Postoperative
      complications occurred in 45% of the patients. Wound healing disturbance (18%)
      and deep infection (15%) were the most predominant. Less frequent complications
      included dislocation, which occurred in nine patients and mechanical
      complications including 5 breakages and 2 aseptic loosening. CONCLUSION: The
      modular hemipelvic endoprosthesis can provide a versatile reconstruction option
      for a variety of pelvic defects with an acceptable rate of complication. Wide
      margins whenever possible should be the goal for these complex patients.

PMID- 23131429
TI  - Can parametrectomy be avoided in early cervical cancer? An algorithm for the
      identification of patients at low risk for parametrial involvement.
AB  - AIMS: To assess the rate of parametrial involvement in a large cohort of patients
      who underwent radical hysterectomy for cervical cancer and to suggest an
      algorithm for the triage of patients to simple hysterectomy or simple
      trachelectomy. METHODS: Multicenter retrospective study of patients with cervical
      cancer stage I through IIA who underwent radical hysterectomy and pelvic
      lymphadenectomy. The patients were divided into 2 groups according to whether or
      not the parametrium was involved. The two groups were compared with regard to the
      clinical and histopathological variables. Logistic regression of the variables
      potentially assessable prior to definitive hysterectomy such as age, tumor size,
      lymph-vascular space invasion (LVSI) and nodal involvement was performed.
      RESULTS: Five hundred and thirty patients had specific histological data on
      parametrial involvement and in 58 (10.9%) patients, parametria was involved.
      Parametrial involvement was significantly associated with older age, tumors
      larger than 2 cm, deeper invasion, LVSI, involved surgical margins, and the
      presence of nodal metastasis. By triaging patients with a tumor <= 2 cm and no
      LVSI, the parametrial involvement rate was 1.8% (2/112 patients). With further
      triage of patients with negative nodes, the rate of parametrial involvement was
      0% (0/107 patients). CONCLUSION: Using a pre-operative triage algorithm, patients
      with early small lesions, no LVSI and no nodal involvement may be spared radical
      surgical procedures and parametrectomy. Further prospective data are urgently
      needed.

PMID- 23131430
TI  - Outcome and complications of chronically implanted subdural electrodes for the
      treatment of medically resistant epilepsy.
AB  - BACKGROUND: Surgery for medically resistant epilepsy is safe and effective.
      However, when noninvasive techniques are insufficient, then consideration is
      given to invasive electrocorticography (EcoG). OBJECTIVE: The aim of the study
      was to analyze results and complications of subdural electrodes placement in the
      treatment of intractable epilepsy. METHODS: Ninety-one consecutive patients who
      underwent placement of subdural electrodes (1999-2010) were considered for this
      study. All patients underwent a standardized pre-operative evaluation. Invasive
      subdural electrode placement was considered when there were inadequate ictal
      recordings, there was discordance between EEG and neuroimaging or the
      epileptogenic zone was localized near eloquent cortex. RESULTS: Resective
      epilepsy surgery was performed in 70/91 patients (76.9%). Twenty-four out of
      seventy (34.3%) who underwent surgical resection were seizure-free (CL-I) at last
      follow-up. A statistical evaluation revealed a very strong trend for patients
      with positive lesional pre-operative MRI to have improved outcomes compared to
      normal brain MRI population (p=.028). There were 10 surgical related
      complications (11%), but no mortality or permanent morbidity. Statistical
      analysis demonstrated that placement of a subdural grid in any combination was
      statistically significant (p=.01) for surgical complications. CONCLUSIONS:
      Invasive monitoring is a useful and necessary technique for the surgical
      treatment of intractable epilepsy. Careful surveillance is required during the
      monitoring period especially when the patient has undergone large subdural grid
      placement. A good working hypothesis can minimize complications and achieve
      better outcomes.

PMID- 23131431
TI  - U.S. health care: a conundrum and a challenge.
AB  - BACKGROUND: This report was conceived as a contribution to the national debate
      regarding U.S. health care (HC) and as a means of explaining the challenges
      facing U.S. HC to the international readers of WORLD NEUROSURGERY. METHODS: The
      basic economic concepts pertinent to health care, including fundamentals of
      economic theories, gross domestic product (GDP), U.S. revenues and expenditures
      and the U.S. federal deficit and national debt, are discussed at the outset of
      this study. This is followed by a review of the U.S. health insurance paradigms
      and a detailed analysis of the escalating cost of U.S. health care. Finally, the
      efforts designed to reverse the paradigm of escalating health care costs will be
      discussed. RESULTS: This study reveals that should the U.S. HC cost continue to
      escalate at the same rate, HC would consume the entire gross domestic product by
      2070. The root causes for this trend are overutilization of HC, inappropriate
      allocation of HC costs at the end of life, defensive medicine, high-end
      technology and prescription drugs, failure of competitive market forces, and
      administrative costs, inefficiency, and waste. The proposed means of reversing
      this paradigm, including the Patient Protection and Affordable Care Act, are
      discussed in light of their economic and social impact. CONCLUSIONS: The reversal
      of the current paradigm of escalating cost of U.S. HC will require extraordinary
      leadership across the entire spectrum of HC delivery. It is concluded that
      neither the Affordable Care Act nor the Path to Prosperity will succeed unless
      the escalating cost of U.S. HC is reversed. It is hoped that this report
      contributes to that end.

PMID- 23131432
TI  - Neurosurgery in Turkey.

PMID- 23131433
TI  - Proceedings from the Workshop on Palliative Epilepsy Surgery: Why, when, how?:
      Organized by Marina Casazza and Giovanni Broggi on February 2-3, 2012, in Milano,
      Italy.

PMID- 23131434
TI  - Naturalistic study of rider's behaviour in initial training in France: evidence
      of limitations in the educational content.
AB  - This paper analyses motorcycle educational content in a number of French
      motorcycle schools on the basis of a naturalistic study of riders' and trainers'
      behaviour. The aim is to specify the situations delivered in motorcycle schools
      and to study the rider's activity in these situations. The methodology includes
      ethnographic observation within the motorcycle schools and the longitudinal
      monitoring of 14 trainee motorcyclists during their initial training. The
      training situations were described by the combination of audio-visual recordings
      and interviews data (i.e. concomitant or interruptive verbalization, and self
      confrontation data). The results permit to (1) compare the "real" and "official"
      durations of track and on-road training, (2) characterize the real training
      situations, (3) describe the preferred forms of instruction, and (4) conduct an
      in-depth analysis of the situations used during training in traffic. The
      discussion show, in first, the poverty of the training situations which are based
      on the repetition of the exercises in the test, and, in second, disparities
      between the riding situations encountered during training and the demands made by
      riding in natural traffic. The usefulness and the applications of this type of
      approach--based on the integration of the rider's point of view notably by self
      confrontation interview--for understanding real riding behaviours and how such
      approaches could supplement vehicle-based data are discussed in a large
      conclusion.

PMID- 23131435
TI  - High volume image guided injections for the management of chronic tendinopathy of
      the main body of the Achilles tendon.
AB  - OBJECTIVES: Several substances are routinely injected in and around tendons. The
      present study evaluated the long term effects of high volume image guided
      injection (HVIGI) of normal saline, local anaesthetic and aprotinin in athletic
      patients with resistant tendinopathy of the main body of the Achilles tendon.
      DESIGN: Case series. METHODS: The study included a series of 94 athletes (69 men
      and 25 women; average age 37.5 years, range 22-63) with ultrasound confirmed
      tendinopathy of the main body of the Achilles tendon. All the patients had not
      improved after at least three months of conservative management. Patients were
      injected with 10 mL of 0.5% Bupivacaine Hydrochloride, 25 mg aprotinin, and up to
      40 mL of injectable normal saline. We prospectively administered the Victorian
      Institute of Sport Assessment-Achilles tendon (VISA-A) to assess the short- and
      long-term pain and functional improvement. RESULTS: At baseline (n = 94), the
      VISA-A score was 41.7 +/- 23.2 (range 11-60), and had improved to 74.6 +/- 21.4
      (range 71-100) by 12 months (n = 87) (p = 0.003), with no significant difference
      between sexes. CONCLUSION: HVIGI with aprotinin significantly reduces pain and
      improves function in patients with chronic Achilles tendinopathy in the short-
      and long-term follow up.

PMID- 23131436
TI  - Knowledge, behavior and attitudes related to skin cancer prevention among final
      year medical students.

PMID- 23131437
TI  - Mini-open sinus tarsi approach with percutaneous screw fixation of displaced
      calcaneal fractures: a prospective computed tomography-based study.
AB  - BACKGROUND: Open reduction and internal fixation (ORIF) of calcaneal fractures
      using an extended lateral approach results in soft tissue disruption and
      theoretically subtalar joint stiffness. A minimally invasive sinus tarsi approach
      for posterior facet exposure and percutaneous screw fixation of the calcaneal
      body has been implemented. This report details the reduction and stability of the
      internal fixation resulting from this approach. METHODS: Twenty-one consecutive
      patients (18 male, 3 female, 45 +/- 16 years) with 22 calcaneal fractures
      underwent ORIF with minimal exposure through the sinus tarsi for reduction,
      lateral plate fixation, and percutaneous screw fixation. There were nine Sanders
      type II fractures and 13 type III fractures. Sixteen fractures had calcaneocuboid
      joint involvement. Nineteen patients (19 fractures) were available for follow-up
      (mean, 32 +/- 14 months). Two computed tomography scans were obtained on each
      patient, one immediately postoperatively and one after a minimum of 1 year, to
      evaluate reduction and fixation stability, respectively. The posterior facet and
      calcaneocuboid joint were graded excellent, good, fair, or poor, according to
      articular step, defect, and angulation. Any change was considered loss of
      stability. Similarly, on a conventional two-dimensional radiograph, more than 5
      degrees  of Bohler's angle difference was defined as loss of calcaneal height.
      RESULTS: Postoperative posterior facet and calcaneocuboid joint reduction was
      good (step < 1 mm, defect < 5 mm, angulation < 5 degrees ) or excellent (no step,
      defect, angulation) in 14/22 (64%) and 11/16 fractures, respectively. At follow
      up, no loss of reduction at the posterior facet and calcaneocuboid joint was
      noted. More than 5 degrees  of Bohler's angle decrease was found in three
      patients. CONCLUSION: Even complex calcaneal fractures can be sufficiently
      exposed by a minimally invasive sinus tarsi approach for anatomic reduction and
      stable fixation. Most patients had good or excellent functional results, which
      may have resulted from minimal soft tissue disruption.

PMID- 23131438
TI  - Outcome of modified Kidner procedure with subtalar arthroereisis for painful
      accessory navicular associated with planovalgus deformity.
AB  - BACKGROUND: Type II accessory naviculars are frequently associated with
      planovalgus deformity. Operative treatment for patients recalcitrant to
      nonoperative treatment involves resection, with or without takedown, and
      reattachment of the tibialis posterior tendon as described by Kidner. This does
      not address the planovalgus deformity. The authors hypothesized that adding a
      subtalar arthroereisis to the Kidner procedure would lead to improvement of pain
      and function and correction of the deformity. METHODS: Institutional Review Board
      approved, prospectively collected data were reviewed for 20 patients (23 feet),
      who underwent a combined modified Kidner and subtalar arthroereisis for painful
      type II accessory navicular with planovalgus deformity recalcitrant to
      nonoperative treatment. The average age at the time of surgery was 18 years.
      Patients were evaluated preoperatively and at final follow-up clinically,
      radiographically, and via the visual analog pain scale (VAPS), the American
      Orthopaedic Foot and Ankle Society (AOFAS) ankle hindfoot score, and a
      satisfaction rating. Mean follow-up was 53.9 months. RESULTS: The mean AOFAS
      scores improved from 53 preoperatively to 95 at final follow-up and the mean VAPS
      score decreased from 7.4 preoperatively to 1.7 at final follow-up.
      Radiographically, the average Meary's angle improved from 18.5 degrees  apex
      plantar preoperatively to 3 degrees  apex plantar on weight-bearing lateral
      radiographs, and the average talar head uncoverage percentage on weight-bearing
      anteroposterior radiographs improved from 24% preoperatively to 3%. Nineteen of
      20 patients reported good or excellent results. Three patients required implant
      removal because of pain; no recurrence of planovalgus deformity occurred after
      implant removal. No patients developed subtalar arthritis. CONCLUSION: The
      modified Kidner procedure combined with a subtalar arthroereisis resulted in
      significant pain and functional improvement. The deformity correction obtained at
      surgery was maintained even if the arthroereisis plug was removed. The extra
      articular plug did not lead to subtalar arthritis.

PMID- 23131439
TI  - Outcome of medial displacement calcaneal osteotomy for correction of adult
      acquired flatfoot.
AB  - BACKGROUND: The results of medial displacement calcaneal osteotomy (MDCO) with
      flexor digitorum longus (FDL) tendon transfer were reviewed, as well as
      postoperative radiographic changes, to determine quantitative x-ray-based
      indications for MDCO with FDL tendon transfer in cases of adult-acquired
      flatfoot. MATERIALS AND METHODS: Twenty-five patients, ages 42 to 71 years,
      underwent MDCO with FDL tendon transfer for stage II posterior tibial tendon
      dysfunction. Follow-up was 2.6 to 10.2 years. Preoperative and postoperative
      Japanese Society for Surgery of the Foot (JSSF), Foot Function Index, and SF-36
      scores and physical and radiographic findings were compared. Eight measures of
      foot alignment were obtained from weight-bearing radiographs at 3, 6, 9, and 12
      months after surgery and every 6 months thereafter. Differences in scores and
      values over time were analyzed statistically. RESULTS: Average JSSF scores
      improved from 59 preoperatively to 91.3 postoperatively (p < .001). The only x
      ray parameters that improved significantly and showed maintenance of the surgical
      correction were the lateral talometatarsal (LTMT) and tibiocalcaneal (TBC)
      angles. With preoperative LTMT and TBC angles of >25 degrees  and >15 degrees ,
      respectively, correction was inadequate. CONCLUSIONS: It was concluded that
      indications for MDCO with FDL tendon transfer in cases of adult-acquired flatfoot
      are a preoperative LTMT angle of <25 degrees  and hindfoot coronal alignment (TBC
      angle) of <15 degrees .

PMID- 23131440
TI  - Circular external fixator-assisted ankle arthrodesis following failed total ankle
      arthroplasty.
AB  - BACKGROUND: Failed total ankle arthroplasty (TAA) often results in significant
      bone loss and requires salvage arthrodesis. This study quantified the bone loss
      following failed TAA and reports the outcome of seven arthrodesis reconstructions
      using the Ilizarov method. METHODS: A retrospective review of ankle fusions was
      performed for failed TAA to collect the mode of implant failure, presenting limb
      length discrepancy (LLD), total bone defect, postarthrodesis LLD, and treatment
      type (shoe lift versus distraction osteogenesis) and amount (shoe lift or
      lengthening). RESULTS: Four mechanical failures and three infections were found.
      Four of seven cases had prior revision TAAs. Four of seven patients were treated
      with tibiotalar arthrodesis; three of the seven patients required talar resection
      and tibiocalcaneal arthrodesis. The mean presenting LLD was 2.2 (range, 1.2 to
      3.5) cm. The mean time in frame was 197 (range, 146 to 229) days. With a mean
      postexplantation total bone defect of 5.1 (range, 3.7 to 8.5) cm, four of seven
      patients elected tibial lengthening following fusion [mean lengthening 4.6
      (range, 2.5 to 8.0) cm; external fixation index (EFI) 42.6 (range, 16.5 to 55.6)
      days/cm)]. Three of seven patients were treated with a shoe lift [mean lift
      height 2.9 (range 2.5 to 3.2) cm]. There was no failure of fixation, refracture,
      or infection. All patients had a stable plantigrade foot and walked with minimal
      limp. Association for the Study and Application of the Method of Ilizarov (ASAMI)
      functional scores were six good and one fair. ASAMI bone scores were four
      excellent and three good. CONCLUSIONS: Ankle arthrodesis following failed TAA
      results in large LLDs secondary to bone loss during implant failure and
      subsequent explantation. External fixation can produce an excellent fusion rate
      in complex, possibly infected, failed TAAs. Limb length equalization (by either
      distraction osteogenesis or shoe lift) provides a means of obtaining good
      functional outcomes following failed TAA.

PMID- 23131441
TI  - Variability in radiographic medial clear space measurement of the normal weight
      bearing ankle.
AB  - BACKGROUND: Medial clear space (MCS) width on mortise radiographs of the ankle is
      commonly used by clinicians for determining the competence of the deltoid
      ligament in the Weber B supination-external rotation ankle fracture. Significant
      variability exists in the current literature regarding methods of obtaining this
      measure and definition of a normal measure in comparison with a pathologic state.
      METHODS: Seventy-three paired bilateral ankle mortise radiographs that were
      without ankle pathology were retrospectively reviewed. MCS width at two separate
      locations (oblique and perpendicular) and superior clear space (SCS) were
      measured on digital radiographs. A Student's t test was used to compare mean
      values. RESULTS: Mean values (+/- SD) were 3.2 (+/- 0.7)~mm for MCS oblique, 2.6
      (+/- 0.7)~mm for MCS perpendicular, and 3.3 (+/- 0.6)~mm for SCS. A significant
      difference (p < .001) existed for all three measures between males and females.
      MCS oblique was statistically different than MCS perpendicular (p < .001) for all
      patients and for males and females independently. The mean difference between
      paired bilateral radiographs was 0.3 (+/- 0.2)~mm for MCS oblique, 0.6 (+/-
      0.6)~mm for MCS perpendicular, and 0.2 (+/- 0.2)~mm for SCS. CONCLUSIONS: MCS
      width has variability based on the location chosen for measurement and gender.
      Contralateral radiographic comparison of MCS should be routinely used to identify
      pathologic widening versus normal anatomic variation. CLINICAL RELEVANCE: Use of
      single threshold values for MCS width as an operative indicator may produce a
      false-positive diagnosis of deltoid incompetence in Weber B supination-external
      rotation ankle fractures and possibly lead to unnecessary surgery.

PMID- 23131442
TI  - Outcome of transfibular ankle arthrodesis with Ilizarov apparatus.
AB  - BACKGROUND: Both transfibular ankle arthrodesis with fibular onlay grafting and
      ankle arthrodesis using the Ilizarov apparatus have resulted in acceptable fusion
      rates. This study analyzed outcomes in the authors' practice for all patients who
      underwent transfibular ankle arthrodesis with fibular onlay grafting using the
      Ilizarov apparatus. MATERIALS AND METHODS: A retrospective review was conducted
      of all patients who experienced severe ankle pain associated with osteoarthritis,
      rheumatoid arthritis, talar osteonecrosis, or septic arthritis and underwent
      transfibular ankle arthrodesis with an Ilizarov apparatus between 1995 and 2010.
      Postoperative clinical outcomes were evaluated for 42 consecutive patients (43
      feet) who received primary or revision ankle arthrodesis using the Ilizarov
      technique at two centers. Mean duration of follow-up was 4.1 (range, 1.5 to 13)
      years. Outcomes were assessed using the ankle-hindfoot scale of the American
      Orthopaedic Foot and Ankle Society. RESULTS: All ankles fused successfully. Mean
      clinical outcome improved significantly from 36.2 (range, 8 to 64) preoperatively
      to 77.4 (range, 0 to 86; p < .05) postoperatively. CONCLUSION: Transfibular ankle
      arthrodesis using the Ilizarov external fixation system and fibular onlay strut
      grafting can achieve a very high rate of bony union and lead to general
      improvements in clinical outcome. Forefoot stabilization with a forefoot ring
      achieved rigid stabilization resulting in a shorter duration of external
      fixation.

PMID- 23131443
TI  - Union rate of tibiotalocalcaneal nails with internal or external bone
      stimulation.
AB  - INTRODUCTION: The use of bone growth stimulation has been reported in the
      application of hindfoot and ankle arthrodesis. Most studies have been
      retrospective case series with few patients. The authors present a comparative
      analysis of patients undergoing tibiotalocalcaneal (TTC) arthrodesis via a
      retrograde intramedullary arthrodesis nail to evaluate the influence of internal
      versus external bone stimulation in this population. METHODS: One hundred fifty
      four patients were treated with retrograde intramedullary nailing. A
      comprehensive chart and radiographic review was performed from a database of
      patients who underwent TTC fusion with or without bone stimulation. Ninety-one
      patients with retrograde TTC nailing were treated with direct current internal
      bone stimulation at the time of the index procedure (internal group) and 63 were
      treated with combined magnetic field external bone stimulation (external group).
      The primary end point was fusion with potential variables evaluated for influence
      on fusion rates. RESULTS: Demographically the cohorts were similar groups in age
      and comorbidities. Surgical and outcome data were examined, and there were few
      statistically significant differences between the two groups. There was no
      statistically significant difference in rate of union (52.7% and 57.1%, p = .63)
      or rate of complications between the internal and external groups. Overall, the
      success rate for achieving a stable, functional limb for the groups was 81.3%
      (74/91 patients) and 82.5% (52/63 patients) in the internal and external groups,
      respectively (p = .62). CONCLUSION: The authors demonstrated there were no
      statistically significant differences between the union and complication rate
      when comparing these types of internal and external bone stimulation in this
      patient population. Consideration of these results may help guide physicians when
      considering bone stimulation as an adjunct to TTC fusions with a retrograde
      intramedullary nail.

PMID- 23131444
TI  - Effect of increased weight on ankle mechanics and spatial temporal gait mechanics
      in healthy controls.
AB  - BACKGROUND: Ankle osteoarthritis has been associated with trauma, instability,
      and inflammatory arthritis. Limited literature exists examining the effect of
      body weight on ankle joint loading. The purpose of this study was to examine the
      relationship between increased weight and gender on ankle kinematics and
      kinetics. METHODS: Fifty-three (28 male, 25 female) subjects were recruited for
      the study. All subjects underwent a standard level walking gait analysis in four
      different weight conditions (normal, 10%, 15%, and 20% increased body weight).
      Testing order was randomized. A series of mixed-factor, repeated-measures
      analyses of variance (weight by gender) were used to determine statistical
      differences between the groups (p < .05). RESULTS: Walking speed was not
      significantly different between gender or weight conditions. No significant
      differences existed for step length, step time, stride length, swing time, or
      sagittal plane ankle kinematics and kinetics. A significant increase in
      plantarflexion moment existed for the males (p < .05). The peak plantarflexion
      moment increased as weight increased. Single support time (p = .042) was
      significantly different between the no weight and the 15% and 20% increased
      weight conditions. In addition, double support time was significantly longer in
      the males compared with females (p < .001) and significantly increased for each
      weight condition (p < .001). CONCLUSION: Increasing weight alters spatial
      temporal mechanics and sagittal plane ankle kinetics in a healthy control
      population. The effect of increasing weight appears to be similar between
      genders. CLINICAL RELEVANCE: The findings of the present study may be relevant
      for future studies to assess the role of weight as a potential covariate on
      postoperative outcomes and gait mechanics.

PMID- 23131446
TI  - Influence of different anatomical structures on distal soft tissue procedure in
      hallux valgus surgery.
AB  - BACKGROUND: The distal soft tissue procedure is considered to be an effective
      surgical procedure to increase the correction in hallux valgus surgery. The goal
      of this study was to evaluate the efficacy of each single step of the lateral
      release in an experimental setup to assess which surgical steps are essential to
      correct hallux valgus deformity, which steps may be ineffective, and which steps
      may be risky. MATERIALS AND METHODS: Three techniques of lateral release that
      differ in the sequence of surgical steps were evaluated in 15 fresh-frozen
      cadaver feet. After each step, an identical medial capsular reefing was simulated
      and the corrective effects on the metatarsophalangeal (MTP) angle,
      intermetatarsal (IM) angle, and sesamoid subluxation were assessed
      radiographically. RESULTS: Transection of the deep transverse metatarsal ligament
      and the attachment of the adductor hallucis muscle had virtually no corrective
      effect. Dissection of the lateral metatarsosesamoid suspensory ligament following
      incision of the lateral capsule and the lateral collateral ligament allowed
      correction of the MTP and IM angles as well as sesamoid subluxation in all three
      experimental settings. Dissection of the lateral short sesamophalangeal ligament
      and the plantar attachment of the articular capsule led to overcorrection and
      instability of the joint. CONCLUSION: Transecting the lateral metatarsosesamoid
      suspensory ligament was the key to a successful lateral release in this model.
      Release of the deep transverse metatarsal ligament and the adductor hallucis
      muscle did not contribute to hallux valgus correction. The authors believe that
      the lateral short sesamophalangeal ligament and the plantar attachment of the
      articular capsule should be preserved to minimize the risk of possible joint
      instability. CLINICAL RELEVANCE: The results of these study clarify contradictory
      findings in former clinical studies and should be considered in clinical
      practice.

PMID- 23131445
TI  - Locked versus nonlocked plate fixation for first metatarsophalangeal arthrodesis:
      a biomechanical investigation.
AB  - BACKGROUND: First metatarsophalangeal (MTP) arthrodesis using dorsal plate
      fixation is a common procedure for painful conditions of the great toe. Locked
      plates have become increasingly common for arthrodesis procedures in the foot,
      including the hallux MTP joint. The biomechanical advantages and disadvantages of
      these plates are currently unknown. The purpose of this study was to compare
      locked and nonlocked plates used for first MTP fusion for strength and stiffness.
      MATERIALS AND METHODS: The first ray of nine matched pairs of fresh-frozen
      cadaveric feet underwent dissection, preparation with cup-and-cone reamers, and
      fixation of the MTP joint with a compression screw and either a nonlocked or
      locked stainless steel dorsal plate. Each specimen was loaded in a cantilever
      fashion to 90 N at a rate of 3 Hz for a total of 250,000 cycles. The amount of
      plantar MTP gap was recorded using a calibrated extensometer. Load-to-failure
      testing was performed for all specimens that endured the entire cyclical loading.
      Stiffness was calculated from the final load-to-failure test. RESULTS: The locked
      plate group demonstrated significantly less plantar gapping during fatigue
      endurance testing from cycle 10,000 through 250,000 (p < .05). Mean stiffness was
      significantly greater in the locked plate group compared with the nonlocked plate
      group (p = .02). There was no significant difference in load to failure between
      the two groups (p = .27). CONCLUSION: Compared with nonlocked plates, locked
      hallux MTP arthrodesis plates exhibited significantly less plantar gapping after
      10,000 cycles of fatigue endurance testing and significantly greater stiffness in
      load-to-failure testing. CLINICAL RELEVANCE: As the use of locked plate
      technology is becoming increasingly common for applications in the foot, a
      thorough understanding of the biomechanical characteristics of these implants may
      help optimize their indications and clinical use.

PMID- 23131447
TI  - Infections in calcaneal fracture patients treated with open reduction and
      internal fixation and bioresorbable calcium phosphate paste: a case series.

PMID- 23131448
TI  - Tibial plateau fracture following proximal tibia autograft harvest: case report.

PMID- 23131449
TI  - Osseous talofibular impingement after supination-external rotation stage II ankle
      fracture: case report.

PMID- 23131450
TI  - Anteromedial approach for ankle arthoplasty and arthrodesis: technique tip.

PMID- 23131451
TI  - Late-stage Freiberg's disease treated with dorsal wedge osteotomy and joint
      distraction arthroplasty: technique tip.

PMID- 23131452
TI  - Medial subtalar arthroscopy.

PMID- 23131453
TI  - Tendoscopic debridement of peroneus quartus muscle for chronic lateral ankle
      pain: a case report.

PMID- 23131454
TI  - Three-portal ankle arthroscopy in prone position with ankle suspended: technique
      tip.

PMID- 23131455
TI  - Current concepts review: risk factors for nonunions in foot and ankle
      arthrodeses.

PMID- 23131458
TI  - Three-step method for ultrasound-guided central vein catheterization.
AB  - BACKGROUND: The long-axis view and in-plane needle approach (LAX-IP) for
      ultrasound-guided central vein catheterization is considered ideal because of the
      quality of real-time imaging. We describe a novel technique, using a step-by-step
      procedure, to overcome the pitfalls associated with the LAX-IP. This study was
      undertaken to demonstrate the clinical utility of this approach. METHODS: All
      operators underwent training before participation in this study. One hundred
      patients were enrolled in this study and underwent central venous catheterization
      using this method. Using a portable ultrasound and vein catheterization kit,
      patients were appropriately positioned and a straight portion of the vein
      identified (Step 1). A needle guide was used (Step 2) and the vein imaged in real
      time in two directions (Step 3), to identify the true long axis and prevent
      damage to surrounding tissues. RESULTS: The overall success rate for
      catheterization was 100% with a median of one puncture for each patient. All
      catheterizations were performed within three punctures. Problems with the first
      puncture included difficult insertion of the guide-wire due to coiling, difficult
      anterior wall puncture, less experience with the procedure, and other reasons.
      There were no complications associated with the procedure. CONCLUSIONS: This
      three-step method is not dependent on an operator's ability to proceed based on
      spatial awareness, but rather depends on logic. This method can prevent
      difficulties associated with a two-dimensional ultrasound view, and may be a
      safer technique compared with others. Further clinical trials are needed to
      establish the safety of this technique.

PMID- 23131459
TI  - Misinterpretation in virus clearance studies of biological products due to an
      uncommon discrepancy between cytopathic effects and infectivity of human
      immunodeficiency virus (HIV).

PMID- 23131460
TI  - FOLD-EM: automated fold recognition in medium- and low-resolution (4-15 A)
      electron density maps.
AB  - MOTIVATION: Owing to the size and complexity of large multi-component biological
      assemblies, the most tractable approach to determining their atomic structure is
      often to fit high-resolution radiographic or nuclear magnetic resonance
      structures of isolated components into lower resolution electron density maps of
      the larger assembly obtained using cryo-electron microscopy (cryo-EM). This
      hybrid approach to structure determination requires that an atomic resolution
      structure of each component, or a suitable homolog, is available. If neither is
      available, then the amount of structural information regarding that component is
      limited by the resolution of the cryo-EM map. However, even if a suitable homolog
      cannot be identified using sequence analysis, a search for structural homologs
      should still be performed because structural homology often persists throughout
      evolution even when sequence homology is undetectable, As macromolecules can
      often be described as a collection of independently folded domains, one way of
      searching for structural homologs would be to systematically fit representative
      domain structures from a protein domain database into the medium/low resolution
      cryo-EM map and return the best fits. Taken together, the best fitting non
      overlapping structures would constitute a 'mosaic' backbone model of the assembly
      that could aid map interpretation and illuminate biological function. RESULT:
      Using the computational principles of the Scale-Invariant Feature Transform
      (SIFT), we have developed FOLD-EM-a computational tool that can identify folded
      macromolecular domains in medium to low resolution (4-15 A) electron density maps
      and return a model of the constituent polypeptides in a fully automated fashion.
      As a by-product, FOLD-EM can also do flexible multi-domain fitting that may
      provide insight into conformational changes that occur in macromolecular
      assemblies.

PMID- 23131461
TI  - Small cell carcinoma of the salivary gland: a systematic literature review and
      two case reports.
AB  - Salivary gland small cell carcinoma is a rare neoplasm, accounting for less than
      1% of salivary gland tumours. Little is known about the epidemiologic factors and
      treatment of this lesion. The authors report two cases and perform a systematic
      literature search from 1960 to 2011 for articles on salivary gland small cell
      carcinoma. Once the papers were reviewed, a database was generated to analyse
      clinical and pathological features, treatments and outcomes, and an attempt was
      made to identify prognostic factors. Available data were retrieved for 44 cases
      which fully satisfied the inclusion criteria; the median age was 64.25 years and
      the male:female ratio was 2.4:1. The parotid gland was the most common site
      (79.6%). The overall 1-, 2- and 5-year survival rates were 75.3%, 56.4% and
      36.6%, respectively. According to the present review, patient age, tumour size,
      distant metastasis and cytokeratin-20 positive immunostaining were all
      significant prognostic factors in a univariate analysis. No particular treatment
      approach appeared to improve survival. This work reinforces knowledge about
      salivary gland small cell carcinoma's epidemiologic features, and identifies new
      prognostic markers. The optimal management of this lesion remains controversial.

PMID- 23131462
TI  - A randomized trial of vitamin D supplementation in 2 community health center
      networks in South Carolina.
AB  - OBJECTIVE: We sought to determine whether 4000 IU/d (vs 2000 IU/d) of vitamin D
      during pregnancy is safe and improves maternal/neonatal 25-hydroxyvitamin D
      [25(OH)D] in a dose-dependent manner. STUDY DESIGN: A total of 257 pregnant women
      12-16 weeks' gestation were enrolled. Randomization to 2000 vs 4000 IU/d followed
      1-month run-in at 2000 IU/d. Participants were monitored for hypercalciuria,
      hypercalcemia, and 25(OH)D status. RESULTS: Maternal 25(OH)D (n = 161) increased
      from 22.7 ng/mL (SD 9.7) at baseline to 36.2 ng/mL (SD 15) and 37.9 ng/mL (SD
      13.5) in the 2000 and 4000 IU groups, respectively. While maternal 25(OH)D change
      from baseline did not differ between groups, 25(OH)D monthly increase differed
      between groups (P < .01). No supplementation-related adverse events occurred.
      Mean cord blood 25(OH)D was 22.1 +/- 10.3 ng/mL in 2000 IU and 27.0 +/- 13.3
      ng/mL in 4000 IU groups (P = .024). After controlling for race and study site,
      preterm birth and labor were inversely associated with predelivery and mean
      25(OH)D, but not baseline 25(OH)D. CONCLUSION: Maternal supplementation with
      vitamin D 2000 and 4000 IU/d during pregnancy improved maternal/neonatal vitamin
      D status. Evidence of risk reduction in infection, preterm labor, and preterm
      birth was suggestive, requiring additional studies powered for these endpoints.

PMID- 23131464
TI  - Gene expression cross-profiling in genetically modified industrial Saccharomyces
      cerevisiae strains during high-temperature ethanol production from xylose.
AB  - Production of ethanol from xylose at high temperature would be an economical
      approach since it reduces risk of contamination and allows both the
      saccharification and fermentation steps in SSF to be running at elevated
      temperature. Eight recombinant xylose-utilizing Saccharomyces cerevisiae strains
      developed from industrial strains were constructed and subjected to high
      temperature fermentation at 38  degrees C. The best performing strain was
      sun049T, which produced up to 15.2 g/L ethanol (63% of the theoretical
      production), followed by sun048T and sun588T, both with 14.1 g/L ethanol
      produced. Via transcriptomic analysis, expression profiling of the top three best
      ethanol producing strains compared to a negative control strain, sun473T, led to
      the discovery of genes in common that were regulated in the same direction.
      Identification of the 20 most highly up-regulated and the 20 most highly down
      regulated genes indicated that the cells regulate their central metabolism and
      maintain the integrity of the cell walls in response to high temperature. We also
      speculate that cross-protection in the cells occurs, allowing them to maintain
      ethanol production at higher concentration under heat stress than the negative
      controls. This report provides further transcriptomics information in the
      interest of producing a robust microorganism for high-temperature ethanol
      production utilizing xylose.

PMID- 23131463
TI  - The pelvic floor complication scale: a new instrument for reconstructive pelvic
      surgery.
AB  - OBJECTIVE: The purpose of this study was to develop and test a unique, new pelvic
      floor surgery complication scale and compare it with an existing validated
      measure. STUDY DESIGN: Surgeons from 2 clinical trials networks rated
      complications based on perceived patient bother, severity, and duration of
      disability to develop a pelvic floor complication scale (PFCS). PFCS scores were
      calculated for subjects in 2 multicenter pelvic floor surgical trials. The PFCS
      and modified Clavien-Dindo scores were evaluated for associations with length of
      hospitalization, satisfaction, and quality-of-life measures (health utilities
      index, short form-36, urogenital distress inventory, and incontinence impact
      questionnaire). RESULTS: We calculated PFCS scores for 977 subjects. Higher PFCS
      and Clavien-Dindo scores similarly were associated with longer length of
      hospitalization (P < .01), lower satisfaction (P < .01), lower Health Utilities
      Index scores (P = .02), lower short form-36 scores (P = .02), higher urogenital
      distress Inventory scores (P < .01), and incontinence impact questionnaire scores
      (P < .01) at 3 months. No associations were present at 1 year. CONCLUSION: The
      PFCS compares favorably to the validated modified Clavien-Dindo instrument.

PMID- 23131465
TI  - The risk of small ruminant lentivirus (SRLV) transmission with reproductive
      biotechnologies: state-of-the-art review.
AB  - Reproductive biotechnologies are essential to improve the gene pool in small
      ruminants. Although embryo transfer (ET) and artificial insemination (AI) greatly
      reduce the risk of pathogen transmission, few studies have been performed to
      quantify this risk. The aim of this review is to contribute to the elements
      needed to evaluate the risk of lentivirus transmission in small ruminants (SRLV)
      during ET, from embryos produced in vitro or in vivo, and with the use of the
      semen destined for AI. The purpose is to consider the genetic possibilities of
      producing uninfected embryos from infected females and males or bearers of the
      SRLV genome. We have reviewed various studies that evaluate the risk of SRLV
      transmission through genital tissues, fluids, cells, and flushing media from
      female and male animals. We have only included studies that apply the
      recommendations of the International Embryo Transfer Society, to obtain SRLV-free
      offspring from infected female animals using ET, and the justification for using
      healthy male animals, free from lentivirus, as semen donors for AI. As such, ET
      and AI will be used as routine reproductive techniques, with the application of
      the recommendations of the International Embryo Transfer Society and World
      Organization for Animal Health.

PMID- 23131466
TI  - Ovarian characteristics, serum concentrations of progesterone and estradiol, and
      fertility in lactating dairy cows in response to equine chorionic gonadotropin.
AB  - We hypothesized that administration of eCG during the proestrous maturation phase
      of the preovulatory ovarian follicle would increase follicle size and serum
      estradiol concentrations. Our objectives were to evaluate the effects of eCG
      administration on preovulatory ovarian follicle size and growth rate, serum
      concentrations of estradiol and progesterone, estrual activity, posttreatment
      luteal activity, and pregnancy per AI. Lactating Holstein cows milked thrice
      daily were enrolled in a Presynch-Ovsynch timed AI program before the first AI.
      Cows (N = 128) in a single herd were given two doses of prostaglandin F(2alpha)
      (PGF(2alpha)) 14 days apart (Presynch), with the second dose 11 days before the
      onset of an Ovsynch protocol (treatment with GnRH 7 days before and 56 hours
      after PGF(2alpha), with AI 16 to 18 hours after the second GnRH treatment). Cows
      were assigned randomly to receive either saline or 400 IU eCG concurrent with
      PGF(2alpha) treatment of the Ovsynch protocol (Day 0). Serum concentrations of
      progesterone and estradiol were assessed to determine if eCG would increase
      estrual activity, improve ovulatory response to GnRH, and enhance postovulatory
      luteal function. Compared with controls, treatment with eCG did not increase
      diameter or growth rate of the largest follicle during 48 hours after eCG, but
      tended (P = 0.09) to increase growth rate of the second largest follicle. Serum
      estradiol concentrations and estrual activity were not altered by eCG. Serum
      progesterone concentrations did not differ between treatments on Days 0, 2, 4, 9,
      or 16 after eCG treatment. Number of CL per cow on Days 9 and 16 after
      administration of eCG did not differ between treatments, but total luteal tissue
      volume tended (P = 0.06) to be greater on Day 16 for eCG-treated cows compared
      with controls. Pregnancy per AI at first service was similar between eCG (35.3%)
      and control cows (39.0%). We concluded that eCG treatment administered 3 days
      before insemination at the dose of 400 IU failed to increase follicle growth size
      and growth rate 48 hours after treatment, and did not enhance pregnancy outcomes
      in dairy cattle programmed for AI at first service.

PMID- 23131467
TI  - 'Leveling' the playing field for analyses of single-base resolution DNA
      methylomes.

PMID- 23131468
TI  - Guanylate cyclase-C receptor activation: unexpected biology.
AB  - Guanylate cyclase-C (GC-C) is a transmembrane receptor activated by bacterial
      heat-stable enterotoxins and by the endogenous hormones guanylin and uroguanylin.
      GC-C plays key roles in the regulation of intestinal fluid and electrolyte
      homeostasis. This is highlighted by several recently identified human mutations
      in GUCY2C, the gene encoding GC-C, which leads to the respective gain or loss of
      function of GC-C, resulting in profound effects on gastrointestinal function.
      However, a wealth of recent studies indicates GC-C signalling extends to a
      multitude of diverse additional functions. Recent pre-clinical and clinical
      studies demonstrate a novel first-in-class GC-C activating peptide, Linaclotide,
      provides effective relief from constipation and abdominal pain in patients with
      chronic constipation and constipation-predominant Irritable Bowel Syndrome.
      Accumulating evidence also suggests GC-C plays protective roles in mucosal
      barrier function, tissue injury and inflammation, whilst GC-C signalling is a key
      regulator of intestinal cell proliferation and apoptosis. Finally, recently
      identified extra-intestinal GC-C signalling pathways make novel contributions to
      the regulation of food intake and symptoms associated with Attention Deficit
      Hyperactivity Disorder. Consequently, these findings provide GC-C expression and
      its associated mutations as potential diagnostic markers for disease. They also
      provide current and future therapeutic potential for GC-C signalling within and
      outside the gastrointestinal tract.

PMID- 23131469
TI  - Erythema dyschronicum perstans showing an ash-colored hyperpigmented lesion and
      an adjacent incompletely hypopigmented lesion surrounded by an erythematous
      border: a boundary spectrum to annular lichenoid dermatitis of youth?

PMID- 23131470
TI  - Adrenal rest tissue in gonads of patients with classical congenital adrenal
      hyperplasia: multicenter study of 45 French male patients.
AB  - OBJECTIVES: Several cases of testicular adrenal rest tumours have been reported
      in men with congenital adrenal hyperplasia (CAH) due to the classical form of 21
      hydroxylase deficiency but the prevalence has not been established. The aims of
      this report were to evaluate the frequency of testicular adrenal rest tissue in
      this population in a retrospective multicentre study involving eight
      endocrinology centres, and to determine whether treatment or genetic background
      had an impact on the occurrence of adrenal rest tissue. MATERIAL AND METHODS:
      Testicular adrenal rest tissue (TART) was sought clinically and with ultrasound
      examination in forty-five males with CAH due to the classical form of 21
      hydroxylase deficiency. When the diagnosis of testicular adrenal rest tumours was
      sought, good observance of treatment was judged on biological concentrations of
      17-hydroxyprogesterone (17OHP), delta4-androstenedione, active renin and
      testosterone. The results of affected and non-affected subjects were compared.
      RESULTS: TART was detected in none of the 18 subjects aged 1 to 15years but was
      detected in 14 of the 27 subjects aged more than 15years. Five patients with an
      abnormal echography result had no clinical signs. Therapeutic control evaluated
      at diagnosis of TART seemed less effective when diagnosis was made in patients
      with adrenal rest tissue compared to TART-free subjects. Various genotypes were
      observed in patients with or without TART. CONCLUSION: Due to the high prevalence
      of TART in classical CAH and the delayed clinical diagnosis, testicular
      ultrasonography must be performed before puberty and thereafter regularly during
      adulthood even if the clinical examination is normal.

PMID- 23131472
TI  - Street racing video games and risk-taking driving: An Internet survey of
      automobile enthusiasts.
AB  - PURPOSE: The purpose of this study was to examine the relationships among risky
      driving attitudes, self-perceptions as a risky driver, playing of "drive'em up"
      (which rewarded players for frequent traffic and other violations) and "circuit"
      racing video games as well as self-reported risky driving through a web-based
      survey of car and racing club members in relation to a socio-cognitive model of
      the effects of racing video game playing. METHOD: An Internet questionnaire was
      developed and included: (1) self-perceptions as a risky driver scales (Driver
      Thrill Seeking and Competitive Attitude Toward Driving); (2) attitudes regarding
      street racing; (3) street racing video game playing, and (4) self-reported risky
      driving (Risk-Taking Driving Scale). A sequential logistic regression was
      performed entering age and driving exposure as control variables in the first
      block, self-perceptions as a risky driver in the second block, attitudes in the
      third block and playing "drive'em up" and "circuit" racing games in the last
      block to examine their effects on self-reported risk-taking driving. RESULTS: A
      total of 503 survey respondents were included in the analyses and only 20%
      reported any risk-taking driving. Higher score on the Competitive Attitude Toward
      Driving Scale, more positive attitudes toward street racing, and more frequent
      reported playing of "drive'em up" video games were associated with higher odds on
      the self-reported Risk-Taking Driving Scale. However, the Driver Thrill Seeking
      Scale and "circuit" video game playing failed to predict self-reported risk
      taking driving. CONCLUSIONS: Self-perceptions as a risky driver, positive
      attitudes toward risky driving and "drive'em up" street-racing games, but not
      "circuit" racing games, are associated with increased risk-taking driving. These
      findings are congruent with experimental studies in which games that reward
      driving violations increased risk taking, suggesting that risk taking may be a
      function of type of street racing game played by affecting self-perceptions as a
      risky driver.

PMID- 23131473
TI  - The effect of three low-cost engineering treatments on driver fatigue: A driving
      simulator study.
AB  - Three engineering treatments were implemented in a driving simulator study to
      assess the effect of road-based measures on alleviating the symptoms of fatigue.
      Using results from previous research on the effect of circadian rhythms on
      fatigue-related crashes, two groups of male drivers were recruited for this
      study: young shift workers under the age of 35, who attended immediately after
      their night shift, and older drivers over the age of 45, who completed the study
      during the 'post lunch dip' period, after consuming lunch. Eye tracking (PERCLOS)
      and lateral driver performance measures were used to assess whether baseline
      measures of fatigue changed after drivers experienced each of the three
      treatments, which included variable message signs, chevrons and rumble strips.
      Results showed a marked difference in these measures between drivers' baseline
      (not fatigued) and experimental (fatigued) visits. There were also some
      reductions in lateral deviation and eye closure (as measured by PERCLOS) when the
      treatments were encountered, but no marked difference between the three
      treatments. These results suggest that in addition to driver- and vehicle-based
      methods currently employed to mitigate the effects of fatigue, the inclusion of
      such engineering measures may help alleviate fatigue-related impairments in
      driving, particularly if such treatments are implemented during long stretches of
      straight monotonous roads which are known to be associated with fatigue-related
      crashes. However, positive effects of the treatments were short lived, prompting
      the need for further investigations on their optimal frequency of presentation
      and combination to achieve maximum impact from these low-cost, road-based
      treatments.

PMID- 23131471
TI  - Down-regulation of alpha-2u globulin in renal mitochondria of STZ-induced
      diabetic rats observed by a proteomic method.
AB  - AIM: To identify the changes of mitochondrial protein expression in diabetic
      renal parenchyma and to characterize their molecular functions and biological
      processes in diabetes. METHODS: Mitochondrial proteins extracted from renal
      parenchyma mitochondria of streptozotocin-induced diabetic rats and normal rats
      were separated by two-dimensional polyacrylamide gel electrophoresis and
      identified by matrix-assisted laser desorption/ionization tandem time-of-flight
      mass spectrometry. RESULTS: Eleven proteins from 533 visualized protein spots
      displayed significant different expressions in mitochondria of diabetic kidneys
      compared with those in normal ones. Among these altered proteins, two proteins
      with the most obvious changes in protein expression were identified as alpha-2u
      globulin (mature protein, named A2) and its proteolytically modified form (named
      A2-fragment) respectively. These proteins were found in mitochondria of male rat
      renal parenchyma and were proved to be down-regulated in diabetic rats
      simultaneously. CONCLUSION: Our results suggest that down-regulation of alpha-2u
      globulin may be associated with an abnormal beta-oxidation of long-chain fatty
      acids during diabetes. The decreased expression of A2-fragment in renal
      mitochondria of diabetic nephropathy may reduce fatty acid beta-oxidation, which
      leads to a diminished energy supply from mitochondria to kidney tissue and the
      deposition of a large number of fatty acids in the kidney, ultimately causing and
      aggravating kidney damage. In conclusion, these findings may be helpful for
      understanding the molecular mechanism of diabetic nephropathy.

PMID- 23131475
TI  - Brief educational reports: a new manuscript category.

PMID- 23131474
TI  - Assessment of injury potential in pediatric bed fall experiments using an
      anthropomorphic test device.
AB  - Falls from beds and other furniture are common scenarios provided to conceal
      child abuse but are also common occurrences in young children. A better
      understanding of injury potential in short-distance falls could aid clinicians in
      distinguishing abusive from accidental injuries. Therefore, this study
      investigated biomechanical outcomes related to injury potential in falls from
      beds and other horizontal surfaces using an anthropomorphic test device
      representing a 12-month-old child. The potential for head, neck, and extremity
      injuries and differences due to varying impact surfaces were examined. Linoleum
      over concrete was associated with the greatest potential for head and neck injury
      compared to other evaluated surfaces (linoleum over wood, carpet, wood,
      playground foam). The potential for severe head and extremity injuries was low
      for most evaluated surfaces. However, results suggest that concussion and humerus
      fracture may be possible in these falls. More serious head injuries may be
      possible particularly for falls onto linoleum over concrete. Neck injury
      potential in pediatric falls should be studied further as limitations in ATD
      biofidelity and neck injury thresholds based solely on sagittal plane motion
      reduce accuracy in pediatric neck injury assessment. In future studies,
      limitations in ATD biofidelity and pediatric injury thresholds should be
      addressed to improve accuracy in injury potential assessments for pediatric short
      distance falls. Additionally, varying initial conditions or pre-fall positioning
      should be examined for their influence on injury potential.

PMID- 23131477
TI  - Advance directives in the emergency department.

PMID- 23131478
TI  - Predicting community emergency medicine needs and emergency physician
      compensation modeling; two sides of the same coin?

PMID- 23131479
TI  - Feasibility and speed of insertion of seven supraglottic airway devices under
      simulated airway conditions.
AB  - OBJECTIVES: Endotracheal intubation (ETI) is considered the gold standard for
      protecting the airway. Alternative devices for airway protection have been
      developed that can be used by untrained personnel, by those with less experience,
      and for when ETI is not possible. The main goals of our study were to evaluate
      the success rate and speed of insertion of different supraglottic airway devices
      and to determine whether the devices could be properly inserted under simulated
      critical conditions. METHODS: Fifty medical students used an airway simulation
      trainer (Laerdal SimMan 3G) to assess the success rate and time used to insert
      seven different supraglottic airway devices under simulated physiologic and
      pathologic conditions in two different runs. RESULTS: Although all airway devices
      could be inserted without problems, only the Combitube and the EasyTube could be
      successfully inserted in simulations of trismus, limited mobility of the cervical
      spine, or a combination of pathologic conditions such as trismus plus limited
      mobility of the spine and trismus plus tongue edema. The insertion time was
      significantly longer with LMA Unique, Fastrach, and I-Gel devices in both the
      first and second runs. CONCLUSION: The Combitube and the EasyTube were most
      easily inserted under simulated conditions such as trismus, limited mobility of
      the cervical spine, and combined pathologic conditions. Although all devices are
      useful for establishing an airway by nontrained medical students in standard
      simulations, we suggest that the Combitube and the EasyTube may offer advantages
      in difficult airway situations.

PMID- 23131480
TI  - Skin and soft tissue infections caused by methicillin-resistant Staphylococcus
      aureus (MRSA): an affliction of the underclass.
AB  - OBJECTIVE: The objective of this study was to determine whether skin and soft
      tissue infections (SSTIs) caused by methicillin-resistant Staphylococcus aureus
      (MRSA) in patients presenting to The Ottawa Hospital emergency departments
      (TOHEDs) differed from SSTIs caused by methicillin-susceptible Staphylococcus
      aureus (MSSA) with regard to risk factors, management, and outcomes. METHODS: All
      patients seen at TOHEDs in 2006 and 2007 with SSTIs who yielded MRSA or MSSA in
      cultures from the site of infection were eligible for inclusion. We excluded
      patients with decubitus ulcers and infections related to diabetes or peripheral
      vascular disease. We used an unmatched case-control design. Cases were defined as
      patients with MRSA isolated from the infection site, and controls were defined as
      patients with MSSA isolated from the infection site. Data were collected
      retrospectively from health records and laboratory and hospital information
      systems. RESULTS: A total of 153 patients were included in the study (81 cases
      and 72 controls). The mean age of cases was 37 years, compared to 47 years for
      the controls (p < 0.001). Cases were more likely to have transient residence (31%
      v. 3% [OR 15.6, 95% CI 3.9-61.8, p < 0.001]), present with abscesses (64% v. 15%
      [OR 9.9, 95% CI 4.3-23.7, p < .001]), have a documented history of hepatitis C
      infection (28% v. 3% [OR 13.9, 95% CI 3.9-55.0, p < 0.001]), and have a history
      of substance abuse (53% v. 10% [OR 10.5, 95% CI 4.4-25.1, p < 0.001]). Cases most
      commonly used crack cocaine and injection drugs. CONCLUSION: SSTIs caused by MRSA
      at TOHEDs mainly occur in a population that is young and transient with
      comorbidities such as hepatitis C and substance abuse.

PMID- 23131481
TI  - The SCRAP Rule: The derivation and internal validation of a clinical decision
      rule for computed tomography of the chest in blunt thoracic trauma.
AB  - OBJECTIVE: To derive and internally validate a clinical decision rule that will
      rule out major thoracic injury in adult blunt trauma patients, reducing the
      unnecessary use of chest computed tomographic (CT) scans. METHODS: Data were
      retrospectively obtained from a chart review of all trauma patients presenting to
      a Canadian tertiary trauma care centre from 2005 to 2008, with those from April
      2006 to March 2007 being used for the validation phase. Patients were included if
      they had an Injury Severity Score > 12 and chest CT at admission or a documented
      major thoracic injury noted in the trauma database. Patients with penetrating
      injury, a Glasgow Coma Scale (GCS) score <= 8, paralysis, or age < 16 years were
      excluded. RESULTS: There were 434 patients in the derivation group and 180 in the
      validation group who met the inclusion criteria. Using recursive partitioning,
      five clinical variables were found to be particularly predictive of injury. When
      these variables were normal, no patients had a major thoracic injury (sensitivity
      100% [95% CI 98.4-100], specificity 46.9% [95% CI 44.2-46.9], and negative
      likelihood ratio 0.00 [95% CI 0.00-0.04]). The five variables were oxygen
      saturation (< 95% on room air or < 98% on any supplemental oxygen), chest
      radiograph, respiratory rate >= 25, chest auscultation, and thoracic palpation
      (SCRAP). In the validation group, the same five variables had a sensitivity of
      100% (95% CI 96.2-100%), a specificity of 44.7% (95% CI 39.5-44.7%), and negative
      likelihood ratio of 0.00 (95% CI 0.00-0.10). CONCLUSIONS: In major blunt trauma
      with a GCS score > 8, the SCRAP variables have a 100% sensitivity for major
      thoracic injury in this retrospective study. These findings need to be
      prospectively validated prior to use in a clinical setting.

PMID- 23131482
TI  - Crisis Resources for Emergency Workers (CREW II): results of a pilot study and
      simulation-based crisis resource management course for emergency medicine
      residents.
AB  - OBJECTIVES: Emergency department resuscitation requires the coordinated efforts
      of an interdisciplinary team. Aviation-based crisis resource management (CRM)
      training can improve safety and performance during complex events. We describe
      the development, piloting, and multilevel evaluation of "Crisis Resources for
      Emergency Workers" (CREW), a simulation-based CRM curriculum for emergency
      medicine (EM) residents. METHODS: Curriculum development was informed by an a
      priori needs assessment survey. We constructed a 1-day course using simulated
      resuscitation scenarios paired with focused debriefing sessions. Attitudinal
      shifts regarding team behaviours were assessed using the Human Factors Attitude
      Survey (HFAS). A subset of 10 residents participated in standardized pre- and
      postcourse simulated resuscitation scenarios to quantify the effect of CREW
      training on our primary outcome of CRM performance. Pre/post scenarios were
      videotaped and scored by two blinded reviewers using a validated behavioural
      rating scale, the Ottawa CRM Global Rating Scale (GRS). RESULTS: Postcourse
      survey responses were highly favourable, with the majority of participants
      reporting that CREW training can reduce errors and improve patient safety. There
      was a nonsignificant trend toward improved team-based attitudes as assessed by
      the HFAS (p  =  0.210). Postcourse performance demonstrated a similar trend
      toward improved scores in all categories on the Ottawa GRS (p  =  0.16).
      CONCLUSIONS: EM residents find simulation-based CRM instruction to be useful,
      effective, and highly relevant to their practice. Trends toward improved
      performance and attitudes may have arisen because our study was underpowered to
      detect a difference. Future efforts should focus on interdisciplinary training
      and recruiting a larger sample size.

PMID- 23131483
TI  - The Simulation Olympics: a resuscitation-based simulation competition as an
      educational intervention.
AB  - The Department of Emergency Medicine at Queen's University developed,
      implemented, and evaluated an interprofessional simulation-based competition
      called the Simulation Olympics with the purpose of encouraging health care
      providers to practice resuscitation skills and foster strong team-based
      attitudes. Eleven teams (N  =  45) participated in the competition. Teams
      completed three standardized resuscitation scenarios in a high-fidelity
      simulation laboratory with teams composed of nurses, respiratory therapists, and
      undergraduate and postgraduate medical trainees. Trained standardized actors and
      a dedicated technician were used for all scenarios. Judges evaluated team
      performance using standardized assessment tools. All participants (100%)
      completed an anonymous two-page questionnaire prior to the competition assessing
      baseline characteristics and evaluating participant attitudes, motivation, and
      barriers to participation. The majority of participants (71%) completed an
      evaluation form following the event focusing on highlights, barriers to
      participation, and desired future directions. Evaluations were uniformly positive
      in short-answer feedback and attitudinal scoring measures. To our knowledge, the
      Simulation Olympics competition is the first of its kind in Canada to be offered
      at an academic teaching hospital.

PMID- 23131484
TI  - A painful rash.

PMID- 23131486
TI  - Bilateral occult hip fracture.
AB  - One of the most common acute injuries seen in the emergency department is the hip
      fracture. This injury is usually diagnosed by plain radiographs, however these
      fractures are sometimes not obviously apparent. Occult hip fractures present a
      pitfall for emergency department physicians. We present a case of a patient who
      sustained bilateral occult hip fractures. We review the epidemiology of the
      condition, examine what diagnostic studies are available that may help the
      physician avoid missing the occult hip fracture and what the literature tells us
      about the utility of each of these modalities. The prognosis of the occult hip
      fracture along with options for treatment is also discussed.

PMID- 23131487
TI  - Lactic acidosis following intentional overdose by inhalation of salmeterol and
      fluticasone.
AB  - Salmeterol, a long-acting beta2-adrenergic receptor agonist used for the
      treatment of asthma and chronic obstructive pulmonary disease, has an adverse
      effects profile that is similar to that of salbutamol and other beta2-agonists.
      We report a sympathomimetic syndrome with metabolic acidosis and hyperlactatemia
      after intentional inhalation of salmeterol in a suicide attempt. A 16-year-old
      female patient was admitted to the emergency department approximately 2 hours
      after having inhaled 60 puffs of a combination of salmeterol xinafoate 25 MUg and
      fluticasone propionate 50 MUg. She presented in an anxious state with complaints
      of palpitations and chest pain. The electrocardiogram demonstrated sinus
      tachycardia and ST-segment depression in the inferior and anterolateral leads.
      Laboratory findings showed hypokalemia, hypophosphatemia, and lactic acidosis.
      Cardiac troponin I and creatine kinase MB remained within the normal range.
      Treatment was supportive and included intravenous fluids and cautious potassium
      supplementation. The next day, electrocardiographic and laboratory findings
      returned to normal. We hypothesize that stimulation of beta2-adrenergic receptors
      by inhalation of salmeterol caused this patient's lactic acidosis. This
      observation is consistent with the hypothesis that the hyperlactatemia observed
      during asthma attacks is due in part to the administration of high doses of beta2
      agonists. Salmeterol overdose by inhalation appears to be sufficient to cause
      lactic acidosis.

PMID- 23131490
TI  - Allogeneic hematopoietic cell transplantation for XIAP deficiency: an
      international survey reveals poor outcomes.
AB  - There have been no studies on patient outcome after allogeneic hematopoietic cell
      transplantation (HCT) in patients with X-linked inhibitor of apoptosis (XIAP)
      deficiency. To estimate the success of HCT, we conducted an international survey
      of transplantation outcomes. Data were reported for 19 patients. Seven patients
      received busulfan-containing myeloablative conditioning (MAC) regimens. Eleven
      patients underwent reduced intensity conditioning (RIC) regimens predominantly
      consisting of alemtuzumab, fludarabine, and melphalan. One patient received an
      intermediate-intensity regimen. Survival was poor in the MAC group, with only 1
      patient surviving (14%). Most deaths were from transplantation-related
      toxicities, including venoocclusive disease and pulmonary hemorrhage. Of the 11
      patients who received RIC, 6 are currently surviving at a median of 570 days
      after HCT (55%). Preparative regimen and HLH activity affected outcomes, and of
      RIC patients reported to be in remission from HLH, survival is 86% (P = .03). We
      conclude that MAC regimens should not be used for patients with XIAP deficiency.
      It is possible that the loss of XIAP and its antiapoptotic functions contributes
      to the high incidence of toxicities observed with MAC regimens. RIC regimens
      should be pursued with caution and, if possible, efforts should be made to ensure
      HLH remission before HCT in these patients.

PMID- 23131491
TI  - African swine fever virus serodiagnosis: a general review with a focus on the
      analyses of African serum samples.
AB  - African swine fever (ASF) is an infectious disease that causes heavy mortality in
      domestic pigs. At present there is no vaccine against ASF, and eradication in
      countries where the disease is endemic is based only on competent diagnosis
      programs and the sacrifice of infected animals. Due to the presence of natural
      attenuated strains, certain infection conditions may result in reduced mortality.
      In these situations, the disease can be diagnosed by detection of specific
      antibodies. The use of classical and validated diagnosis assays, such as ELISA
      and Indirect Immunofluorescence or Immunoblotting, allowed the eradication of ASF
      in the Iberian Peninsula in the 1990s. However, given that conventional tests
      include the use of antigens obtained from ASF virus (ASFV)-infected cells, they
      have several disadvantages, such as difficulties to achieve standardization and
      also the risks associated with the manipulation of live virus. Such drawbacks
      have led to the development of alternative and more robust systems for the
      production of ASFV antigens for use in anti-ASFV antibody detection systems. In
      the present review, we provide an update on current knowledge about antigen
      targets for ASFV serodiagnosis, the significant progress made in recombinant
      antigen production, and the refinement of ASF serological diagnostic assays.
      Moreover, we describe the accuracy of an ELISA developed for the serodiagnosis of
      ASFV in Africa. This assay is based on a novel p30 recombinant protein (p30r)
      obtained from an Eastern African viral isolate (Morara strain), which shares 100%
      amino acid sequence identity with the Georgia virus isolate. That study included
      the analyses of 587 field sera collected from domestic pigs and warthogs in
      Senegal (West Africa), the Democratic Republic of Congo (Central Africa),
      Mozambique (South-East Africa), and South Africa. The results revealed that the
      novel p30r-based ELISA allows the accurate detection of antibodies against ASFV,
      independently of the geographical origin of the sera.

PMID- 23131492
TI  - Virological diagnosis of African swine fever--comparative study of available
      tests.
AB  - The rapid and reliable detection of African swine fever virus (ASFV) is essential
      both for timely implementation of control measures to prevent the spread of
      disease, and to differentiate African swine fever (ASF) from other pig disease
      with similar clinical presentations. Many virological tests are currently
      available for the detection of ASFV (live virus), antigen and genome, including
      virus isolation, ELISA, fluorescent antibody, polymerase chain reaction (PCR) and
      isothermal assays. In recent years real-time PCR (rPCR) has become one of the
      most widely used formats for virological diagnosis providing sensitive, specific
      and swift detection and quantification of ASFV DNA. The ability to integrate rPCR
      into automated platforms increases sample throughput and decreases the potential
      for cross-contamination. In more recent years isothermal assays, which are a
      lower-cost alternative to PCR more suitable for use in non-specialised or mobile
      laboratories, have been developed for the detection of ASFV, however these assays
      have not been fully validated for routine use in the field. The performance of
      all virological detection assays in ASF diagnostics, as well as prospects for
      improving diagnostic strategies in the future, are discussed and reviewed in this
      chapter.

PMID- 23131493
TI  - Folding of outer membrane proteins.
AB  - Outer membrane proteins (OMPs) represent a large group of beta-barrel proteins
      found both in the membranes of both bacteria and eukaryotes. Their general ease
      of expression and refolding and straightforward methods to monitor their degree
      of folding conspire to make OMPs excellent model systems to investigate how the
      membrane environment and other biological factors modulating the membrane
      insertion and folding of OMPs influence the folding pathway. This review attempts
      to provide an overview of how these proteins are studied in vitro and what kind
      of information can reliably be extracted. Numerous choices have to be made in
      setting the conditions for successful folding/unfolding, and here a major
      challenge remains to identify conditions that lead to completely reversible
      folding without any hysteresis. Recent progress indicates that this is possible
      through rigorous optimization, such as the use of relatively extreme pH and
      phospholipids with short chain lengths. OMPs are generally kinetically very
      stable, which means that they both fold and unfold very slowly. Many OMPs cannot
      even unfold when embedded in lipid vesicles, but recent work has demonstrated
      that surfactants can provide a useful alternative which can lead to a complete
      description of the kinetics of folding and unfolding of an OMP. The recent report
      of the first protein engineering study of an OMP has demonstrated that it may
      soon be possible to have almost atomic-level resolution of an OMP folding
      mechanism. Combining this insight with the biological complexity of the membrane
      environment constitutes an exciting new frontier in membrane protein science.

PMID- 23131494
TI  - Effective prediction of biodiversity in tidal flat habitats using an artificial
      neural network.
AB  - Accurate predictions of benthic macrofaunal biodiversity greatly benefit the
      efficient planning and management of habitat restoration efforts in tidal flat
      habitats. Artificial neural network (ANN) prediction models for such biodiversity
      were developed and tested based on 13 biophysical variables, collected from 50
      sites of tidal flats along the coast of Korea during 1991-2006. The developed
      model showed high predictions during training, cross-validation and testing.
      Besides the training and testing procedures, an independent dataset from a
      different time period (2007-2010) was used to test the robustness and practical
      usage of the model. High prediction on the independent dataset (r = 0.84)
      validated the networks proper learning of predictive relationship and its
      generality. Key influential variables identified by follow-up sensitivity
      analyses were related with topographic dimension, environmental heterogeneity,
      and water column properties. Study demonstrates the successful application of ANN
      for the accurate prediction of benthic macrofaunal biodiversity and understanding
      of dynamics of candidate variables.

PMID- 23131495
TI  - Carboplatin dose calculation in lung cancer patients with low serum creatinine
      concentrations using CKD-EPI and Cockcroft-Gault with different weight
      descriptors.
AB  - STUDY OBJECTIVES: Carboplatin dosing using the Calvert and Cockcroft-Gault
      formulae in patients with low serum creatinine levels is discussed
      controversially. We conducted a retrospective analysis applying the CKD-EPI
      formula and the alternate size descriptors adjusted body weight and predicted
      normal weight in the Cockcroft-Gault equation for calculating the carboplatin
      dose. METHODS: Data were collected retrospectively from 128 lung cancer patients
      with serum creatinine <0.8 mg/dL (71 MUmol/L) who had received chemotherapy that
      was mostly platinum-based. Serum creatinine concentration for renal function
      estimation and measured creatinine clearance (24-h urine collection) were
      available on the same day from these patients. Actual doses were calculated based
      on the Cockcroft-Gault formula with total body weight. For the study purpose
      doses were recalculated using Cockcroft-Gault with adjusted body weight and
      predicted normal weight and CKD-EPI. Subgroup analyses were performed for gender
      and body mass index. RESULTS: All alternate dose calculations were not inferior
      to the calculation based on Cockcroft-Gault using total body weight. In
      overweight and obese patients they were superior in reducing mean overdose from
      24% to roughly 15% (predicted normal weight, CKD-EPI) and 10% (adjusted body
      weight) and from 25% to 9%, 8% and 4%, respectively. Best performed the
      combination of Cockcroft-Gault with adjusted body weight. CONCLUSION: The results
      show that application of the alternate size descriptor adjusted body weight in
      the Cockcroft-Gault equation can improve dosing accuracy especially in overweight
      and obese patients with low serum creatinine levels.

PMID- 23131496
TI  - Reduced Mycobacterium tuberculosis association with monocytes from diabetes
      patients that have poor glucose control.
AB  - The re-emerging importance of type 2 diabetes mellitus (DM) to tuberculosis (TB)
      control is of growing concern, but the basis for this relationship is poorly
      understood. Given the importance of mononuclear phagocytes for TB control and the
      reported alterations in monocytes of DM patients, we evaluated whether the
      initial interaction between both was affected in diabetics. Mycobacterium
      tuberculosis-naive individuals with and without DM were group matched by age and
      gender and the efficiency of M. tuberculosis association (attachment and
      ingestion) with their monocytes was assessed in the presence of autologous serum.
      The association of M. tuberculosis with monocytes was significantly lower in
      diabetics (19.2 +/- 6.1) than non-diabetics (27.5 +/- 7.9; p = 0.02).
      Multivariate analysis controlling for host socio demographics, DM characteristics
      and serum lipids indicated that male gender (p = 0.04) and poorly-controlled DM
      (high HbA1c and hyperglycemia; p = 0.01) were significantly associated with the
      lower interaction of M. tuberculosis with monocytes. Serum heat-inactivation
      reduced the association of M. tuberculosis to similar levels in both study groups
      (p = 0.69) suggesting alterations in the complement pathway of DM patients. These
      findings suggest an altered route of entry of the pathogen in DM patients that
      may influence the downstream activation of signaling pathways in the monocyte and
      the survival of mycobacteria.

PMID- 23131497
TI  - Phytotoxicity, bioaccumulation and degradation of isoproturon in green algae.
AB  - Isoproturon (IPU) is a pesticide used for protection of land crops from weed or
      pathogen attack. Recent survey shows that IPU has been detected as a contaminant
      in aquatic systems and may have negative impact on aquatic organisms. To
      understand the phytotoxicity and potential accumulation and degradation of IPU in
      algae, a comprehensive study was performed with the green alga Chlamydomonas
      reinhardtii. Algae exposed to 5-50 MUg L(-1) IPU for 3d displayed progressive
      inhibition of cell growth and reduced chlorophyll fluorescence. Time-course
      experiments with 25 MUg L(-1) IPU for 6d showed similar growth responses. The 72
      h EC50 value for IPU was 43.25 MUg L(-1), NOEC was 5 MUg L(-1) and LOEC was 15
      MUg L(-1). Treatment with IPU induced oxidative stress. This was validated by a
      group of antioxidant enzymes, whose activities were promoted by IPU exposure. The
      up-regulation of several genes coding for the enzymes confirmed the observation.
      IPU was shown to be readily accumulated by C. reinhardtii. However, the alga
      showed a weak ability to degrade IPU accumulated in its cells, which was best
      presented at the lower concentration (5 MUg L(-1)) of IPU in the medium. The
      imbalance of accumulation and degradation of IPU may be the cause that resulted
      in the detrimental growth and cellular damage.

PMID- 23131498
TI  - Spherical polystyrene-supported nano-Fe3O4 of high capacity and low-field
      separation for arsenate removal from water.
AB  - Fe(3)O(4) is a promising material for arsenic sequestration due to its specific
      affinity toward arsenic and feasible magnetic separation. How to further increase
      its adsorption capacity while maintain its low-field separation is an interesting
      but challenging task. In this study nano-Fe(3)O(4) was successfully coated onto
      the outer surface of polystyrene (PS) beads of 350-400 nm in diameter by the
      hetero-coacervation method, and the resulting composite PS-Fe(3)O(4) was
      characterized using transmission electron microscope (TEM), X-ray powder
      diffraction (XRD), and electrophoresis measurement (EM). Its adsorption toward
      arsenate was investigated as a function of solution pH, arsenic concentration,
      contact time, and coexisting anions. The maximum adsorption capacity of PS
      Fe(3)O(4) was 139.3mg/g Fe(3)O(4), 77.7% greater than that of bulky Fe(3)O(4).
      More attractively, it can be readily separated from water under a low magnetic
      field (<0.035 T). Continuous adsorption-desorption cyclic results demonstrated
      that arsenate-loaded PS-Fe(3)O(4) can be effectively regenerated by NaOH
      solution, and the regenerated composite beads could be employed for repeated use
      without significant capacity loss, indicating that nano-Fe(3)O(4) was steadily
      coated onto the surface of PS beads. Generally, PS beads could be employed as a
      promising host to fabricate efficient composites originated from Fe(3)O(4) or
      other nanoparticles for environmental remediation.

PMID- 23131499
TI  - Removal of perfluorooctanoic acid and perfluorooctane sulfonate via ozonation
      under alkaline condition.
AB  - The elimination of recalcitrant, ubiquitous perfluoroalkyl acids (PFAAs) such as
      perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) is desirable
      for reducing potential human health and environmental risks. We here report the
      degradation of PFOA and PFOS by 85-100% via ozonation under alkaline condition
      being studied at environmentally relevant contaminant concentrations of 50 MUg L(
      1) to 5 mg L(-1), with enhanced removal rates by addition of hydrogen peroxide.
      Enhanced removal is achieved by ozonation pretreatment for 15 min at the ambient
      pH (i.e. 4-5), followed by elevation of pH to 11 and continued ozonation
      treatment for 4h. The ozonation pretreatment resulted in increased degradation of
      PFOA by 56% and PFOS by 42%. The results indicated hydroxyl radical-driven
      degradation of PFOA and PFOS in both treatments by ozone and peroxone under
      alkaline conditions. Wastewaters from electronics and semiconductor fabrication
      plants in the Science Park of Hsinchu city, Taiwan containing PFOA and PFOS have
      been readily treated by ozonation under alkaline condition. Treatment of PFAAs by
      ozone or peroxone proves to be efficient in terms of energy requirement, contact
      time, and removal rate.

PMID- 23131500
TI  - Role of flue gas components in mercury oxidation over TiO2 supported MnOx-CeO2
      mixed-oxide at low temperature.
AB  - MnO(x)-CeO(2) mixed-oxide supported on TiO(2) (Mn-Ce/Ti) was synthesized by an
      ultrasound-assisted impregnation method and employed to oxidize elemental mercury
      (Hg(0)) at 200 degrees C in simulated coal combustion flue gas. Over 90% of Hg(0)
      oxidation was achieved on the Mn-Ce/Ti catalyst at 200 degrees C under simulated
      flue gas representing those from burning low-rank coals with a high gas hourly
      space velocity of 60,000 h(-1). Gas-phase O(2) regenerated the lattice oxygen and
      replenished the chemisorbed oxygen, which facilitated Hg(0) oxidation. HCl was
      the most effective flue gas component responsible for Hg(0) oxidation. 10 ppm HCl
      plus 4% O(2) resulted in 100% Hg(0) oxidation under the experimental conditions.
      SO(2) competed with Hg(0) for active sites, thus deactivating the catalyst's
      capability in oxidizing Hg(0). NO covered the active sites and consumed surface
      oxygen active for Hg(0) oxidation, hence limiting Hg(0) oxidation. Water vapor
      showed prohibitive effect on Hg(0) oxidation due to its competition with HCl and
      Hg(0) for active adsorption sites. This study provides information about the
      promotional or inhibitory effects of individual flue gas components on Hg(0)
      oxidation over a highly effective Mn-Ce/Ti catalyst. Such knowledge is of
      fundamental importance for industrial applications of the Mn-Ce/Ti catalyst in
      coal-fired power plants.

PMID- 23131501
TI  - Ovarian dysfunction and gene-expressed characteristics of female mice caused by
      long-term exposure to titanium dioxide nanoparticles.
AB  - Although numerous studies have described the accumulation of titanium dioxide
      nanoparticles (TiO(2) NPs) in the liver, kidneys, lung, spleen, and brain, and
      the corresponding damage, it is unclear whether or not TiO(2) NPs can be
      translocated to the ovary and cause ovarian injury, thus impairing fertility. In
      the current study, ovarian injury and gene-expressed characteristics in female
      mice induced by intragastric administration of TiO(2) NPs (10mg/kg) for 90
      consecutive days were investigated. Our findings indicated that TiO(2) NPs can
      accumulate in the ovary and result in ovarian damage, cause an imbalance of
      mineral element distribution and sex hormones, decrease fertility or the
      pregnancy rate and oxidative stress in mice. Microarray analysis showed that in
      ovaries from mice treated with TiO(2) NPs compared to controls, 223 genes of
      known function were up-regulated, while 65 ovarian genes were down-regulated. The
      increased expression of Cyp17a1 following TiO(2) NPs treatment suggested that the
      increase in estradiol biosynthesis may be a consequence of increased TiO(2) NPs.
      In addition, the elevated expression of Akr1c18 implied that progesterone
      metabolism was accelerated, thus causing a decrease in the progesterone
      concentration. Taken together, the apparent regulation of key ovarian genes
      supports the hypothesis that TiO(2) NPs directly affects ovarian function.

PMID- 23131502
TI  - Selective degradation of tetracycline antibiotics present in raw milk by
      electrochemical method.
AB  - The dairy industry disposes of a large volume of waste milk with antibiotic
      residues, which is a great cause of much concern in soil and water environments.
      In this study, the electrochemical oxidation of tetracycline antibiotics (TCs) in
      cow's milk was investigated. Milk contains a high concentration of organic
      matter, and the concentrations of TCs residues are extremely low. The effects of
      anode materials and electrolytes on the degradation of oxytetracycline (OTC) were
      investigated. A higher degradation rate for the OTC was attained using the
      inactive anode or a NaCl electrolyte. It was found that a physically adsorbed
      oxidant on the surface of the anode and indirect oxidation using electrogenerated
      hypochlorite could enhance the degradation of OTC in raw milk. The organic
      components in milk samples affected the removal rate of the OTC. The removal rate
      constants for the OTC in raw milk were 2.8-7.7 times higher than the chemical
      oxygen demand values. It was found that electrochemical oxidation could decompose
      low concentrations of TCs in high concentrations of organic matter solutions
      selectively. The results indicate that electrochemical oxidation is an effective
      method for the treatment of TCs in waste milk.

PMID- 23131503
TI  - alpha-Melanocyte-stimulating hormone regulates vascular NO availability and
      protects against endothelial dysfunction.
AB  - AIMS: alpha-Melanocyte-stimulating hormone (alpha-MSH), derived from the
      precursor molecule pro-opiomelanocortin, exerts potent anti-inflammatory actions
      in the vasculature, but its role in circulatory regulation remains unclear.
      Therefore, we sought to investigate whether alpha-MSH could regulate the local
      control of blood vessel tone. METHODS AND RESULTS: Using in vivo and ex vivo
      methods to assess vascular reactivity, we found that alpha-MSH improved
      endothelium-dependent vasodilatation in the mouse aorta and coronary circulation
      without directly contracting or relaxing blood vessels. alpha-MSH promoted
      vasodilatation by enhancing endothelial nitric oxide (NO) formation and by
      improving sensitivity to endothelium-independent blood vessel relaxation. Using
      cultured human endothelial cells to elucidate the involved molecular mechanisms,
      we show that alpha-MSH increased the expression and phosphorylation of
      endothelial NO synthase in these cells. The observed effects were regulated by
      melanocortin 1 (MC1) receptors expressed in the endothelium. In keeping with the
      vascular protective role of alpha-MSH, in vivo treatment with stable analogues of
      alpha-MSH ameliorated endothelial dysfunction associated with aging and diet
      induced obesity in mice. CONCLUSION: The present study identifies alpha-MSH and
      endothelial MC1 receptors as a new signalling pathway contributing to the
      regulation of NO availability and vascular function. These findings suggest
      applicability of alpha-MSH analogues for therapeutic use in pathological
      conditions that are characterized by vascular dysfunction.

PMID- 23131504
TI  - Initial brazilian experience in the treatment of localized prostate cancer using
      a new generation cryotechnology: feasibility study.
AB  - INTRODUCTION: The objective of our study is to present the first Brazilian
      cryoablation experience in the treatment of low and intermediate risk localized
      prostate cancer using 3rd generation cryoablation and real-time biplanar
      transrectal ultrasonography. MATERIALS AND METHODS: Ten Brazilian patients
      underwent primary cryoablation for localized prostate cancer between October 2010
      and June 2011. All patients consented for whole gland primary cryotherapy. The
      procedures were performed by 3rd generation cryoablation with the Cryocare System
      (r) (Endocare, Irvine, California). Preoperative data collection included patient
      demographics along with prostate gland size, Gleason score, serum prostate
      specific antigen, and erectile function status. Operative and post--operative
      assessment involved estimated blood loss, operative time, complications, serum
      PSA level, erectile function status, urinary incontinence, biochemical disease
      free survival (BDFS), and follow-up time. RESULTS: All patients in the study
      successfully underwent whole gland cryoablation. The mean of: age, prostate size,
      PSA level, and Gleason score, was 66.2 years old; 40.7 g; 7.8 ng/mL; and 6
      respectively. All patients were classified as low or moderate D' Amico risk (5
      low and 5 moderate). Erectile dysfunction was present in 50% of patients. The
      estimated blood loss was minimal, operative time was 46.1 minutes. All patients
      that developed erectile dysfunction post-treatment responded to oral or
      intracavernosal medications with early penile rehabilitation. All patients
      maintained urinary continence by the end of a 10 months evaluation period and
      none had biochemical relapse within the mean follow-up of 13 months (7-15
      months). CONCLUSION: Our initial experience shows that cryoablation is a
      minimally invasive option for the treatment of localized prostate cancer. Short
      term data seems to be promising but longer follow-up is necessary to verify
      oncological and functional results.

PMID- 23131505
TI  - Can we predict which patients will evolve to chronic kidney disease after
      nephrectomy for cortical renal tumors?
AB  - INTRODUCTION: While some studies show that patients submitted to radical
      nephrectomy have a higher risk of developing chronic kidney disease (CKD), some
      studies report that carefully selected living kidney donors do not present a
      higher risk for CKD. Here, we aim to study predictive factors of CKD after
      radical nephrectomy. MATERIALS AND METHODS: Between January 2006 to January 2010,
      107 patients submitted to radical nephrectomy for cortical renal tumors at our
      institution were enrolled in this study. Demographic data were recorded, modified
      Charlson-Romano Index was calculated, and creatinine clearance was estimated
      using abbreviated Modification of Diet in Renal Disease (MDRD) study equation.
      Pathological characteristics, surgical access and surgical complications were
      also reviewed. The end-point of the current study was new onset estimated
      glomerular filtration rate (eGFR) less than 60 and less than 45 mL/minute/1.73
      m(2). RESULTS: Age, preoperative eGFR, Charlson-Romano Index and hypertension
      were predictive factors of renal function loss, when the end-point considered was
      eGFR lower than 60 mL/minute/1.73 m(2). Age and preoperative eGFR were predictive
      factors of renal function loss, when the end-point considered was eGFR lower than
      45 mL/minute/ 1.73 m(2). Moreover, each year older increased 1.1 times the risk
      of eGFR lower than 60 and 45 mL/minute/1.73 m(2). After multivariate logistic
      regression, only age remained as an independent predictive factor of eGFR loss.
      CONCLUSION: Age is an independent predictive factor of GFR loss for patients
      submitted to radical nephrectomy for cortical renal tumors.

PMID- 23131506
TI  - A comparative analysis of pelvic floor muscle strength in women with stress and
      urge urinary incontinence.
AB  - AIMS: To assess pelvic floor muscle (PFM) strength in women with stress urinary
      incontinence (SUI) and urge urinary incontinence (UUI). MATERIALS AND METHODS: 51
      women were prospectively divided into two groups, according to the symptoms as
      SUI (G1 = 22) or UUI (G2 = 29). Demographic data, such as number of pads/ 24
      hours, number of micturations/ 24 hours and nocturia, delay time of urgent void
      (i.e., the time period for which an urgent void could be voluntarily postponed),
      number of parity and vaginal deliveries were obtained using a clinical
      questionnaire. Objective urine loss was evaluated by 60-min. Pad Test, subjective
      urine stream interruption test (UST) and visual survey of perineal contraction.
      Objective evaluations of PFM were performed in all patients (vaginal manometry).
      RESULTS: Median of age, mean number of pads / 24 hours, nocturia and warning time
      were significantly higher in UUI comparing to SUI group. During UST, 45.45% in G1
      and 3.44%, in G2, were able to interrupt the urine stream (p < 0.001). The 60
      min. Pad Test was significantly higher in G2 compared to G1 women (2.7 +/- 2.4 vs
      1.5 +/- 1.9 respectively, p = 0.049). Objective evaluation of PFM strength was
      significantly higher in the SUI than in the UUI patients. No statistical
      difference was observed regarding other studied parameters. CONCLUSION: Pelvic
      floor muscle weakness was significantly higher in women with UUI when compared to
      SUI.

PMID- 23131507
TI  - Prognostic value of urethral mobility and valsalva leak point pressure for female
      transobturator sling procedure.
AB  - PURPOSE: To analyze the influence of urethral mobility and Valsalva leak point
      pressure on postoperative outcomes of transobturator sling (TOT) for female
      stress urinary incontinence. MATERIALS AND METHODS: A prospective cohort was
      conducted including 66 patients submitted to TOT from March 2006 to May 2009.
      Urethral hypermobility was defined as mobility >= 30 degrees  on Q-tip test, and
      Valsalva leak point pressure (VLPP) was classified as greater than 60 cmH2O or 60
      and less on preoperative urodynamics. These parameters were compared through well
      defined postoperative objective and subjective success criteria. Intensity of
      urinary leakage and quality of life was analysed by ICIQ-SF. Statistical analysis
      was accomplished and the results rendered significant if p < 0.05. RESULTS: Mean
      follow up was 10 months (3 to 28). Mean age was 55 years (33 to 80), 70% were
      white and 30% African descendent, mean body mass index was 27 (21 to 38), average
      vaginal and abdominal deliveries were 2.8 and 0.5 respectively. A quarter had
      prior stress incontinence surgery. Patients with urethral hypermobility had
      higher objective success rates (98% versus 81.25%, p = 0.04). The subjective
      success rate was also greater in the hypermobility group (84% versus 62.5%), but
      statistical significance was not reached (p = 0.07). VLPP had no influence on
      either objective or subjective postoperative success rates (p = 0.17 and 0.34,
      respectively). In the subgroup analysis, those with low mobility and high VLPP
      had worse objective success rates in comparison to the group with hypermobility
      and low VLPP (p = 0.04) and also in relation to the remaining of the studied
      population. Other possible prognostic factors (previous surgery, mixed
      incontinence, gestational status) had no influence on success rates. CONCLUSIONS:
      High urethral mobility, regardless of the sphincteric status indicated by VLPP,
      is a favorable prognostic factor for tension-free transobturator tape procedure.
      No relationship was demonstrated between postoperative success rates and VLPP.

PMID- 23131508
TI  - Stereological and biochemical analysis of the urethral edges in patients
      submitted to end-to-end anastomosis for bulbar urethral stricture.
AB  - PURPOSE: To study the morphologic alterations in the proximal and distal urethral
      edges from patients submitted to end-to-end bulbar urethroplasty. MATERIALS AND
      METHODS: We analyzed 12 patients submitted to anastomotic urethroplasty to treat
      bulbar strictures less than 2.0 cm in length. After excision of the fibrotic
      segment to a 28Fr urethral caliber, we obtained biopsies from the spongious
      tissue of the free edges (proximal: PROX and distal: DIST). Controls included
      normal bulbar urethras obtained from autopsies of 10 age matched individuals. The
      samples were histologically processed for smooth muscle cells (SMC), elastic
      system fibers and collagen. Stereological analysis was performed to determine the
      volumetric density (Vv) of each element. Also, a biochemical analysis was
      performed to quantify the total collagen content. RESULTS: Vv of SMC was reduced
      in PROX (31.48 +/- 7.01 p < 0.05) and similar in DIST when compared to controls
      (55.65 +/- 9.60%) with no statistical difference. Elastic fibers were increased
      in PROX (25.70 +/- 3.21%; p < 0.05) and were similar to controls in DIST (15.87
      +/- 4.26%). Total collagen concentration in PROX (46.39 +/- 8.20 ug/mg), and DIST
      (47.96 +/- 9.42 ug/mg) did not differ from controls (48.85 +/- 6.91 ug/mg). Type
      III collagen was similarly present in all samples. CONCLUSIONS: After excision of
      the stenotic segment to a caliber of 28Fr, the exposed and macroscopically normal
      urethral edges may present altered amounts of elastic fibers and SMC, but are
      free from fibrotic tissue. When excising the peri-stenotic tissue, the surgeon
      should be more careful in the proximal end, which is the most altered.

PMID- 23131509
TI  - Finasteride for recurrent priapism in children and adolescents: a report on 5
      cases.
AB  - PURPOSE: Recurrent priapism is prevalent in children. Different medications have
      been used to avoid new episodes, however, there is no consensus regarding the
      best option. The use of finasteride to treat priapism in adults has already been
      tested. The aim of the present study was to test the hypothesis that a low dose
      of finasteride would be effective in preventing recurrent priapism in children.
      MATERIALS AND METHODS: Since 2007, five children and adolescents with recurrent
      episodes of priapism have been treated with finasteride in our department, and
      the medical records of these patients were reviewed for this study. In four
      cases, the dose used was 1 mg a day, while the remaining patient used 1 mg twice
      a day. RESULTS: Prior to initiating finasteride treatment, one patient reported
      having had 6 episodes of acute priapism, while the remaining patients had more
      than 10 episodes. One of the patients reported having stuttering priapism almost
      daily. With a mean follow-up of 20 months, four patients had no episodes and only
      one patient complained of sporadic and shorter duration episodes. CONCLUSIONS:
      These initial results suggest that a low daily dose of finasteride appears to
      represent an effective and safe form of treatment for recurrent priapism in
      children and adolescents with SCD. However, in order to confirm these initial
      findings, studies with a large population and a control group are essential.

PMID- 23131510
TI  - Identification of mechanisms involved in the relaxation of rabbit cavernous
      smooth muscle by a new nitric oxide donor ruthenium compound.
AB  - PURPOSE: The aim of this study was to evaluate the relaxation in vitro of
      cavernous smooth muscle induced by a new NO donor of the complex nitrosil
      ruthenium, named trans-[Ru(NH3)4(caffeine)(NO)]C13 (Rut-Caf) and sodium
      nitroprusside (SNP). MATERIALS AND METHODS: The tissues, immersed in isolated
      bath systems, were pre-contracted with phenilephrine (PE) (1 uM) and then
      concentration-response curves (10 (-12) - 10(-4) M) were obtained. To clarify the
      mechanism of action involved, it was added to the baths ODQ (10 uM, 30 uM),
      oxyhemoglobin (10 uM), L-cysteine (100 uM), hydroxicobalamine (100 uM),
      glibenclamide, iberotoxin and apamine. Tissue samples were frozen in liquid
      nitrogen to measure the amount of cGMP and cAMP produced. RESULTS: The substances
      provoked significant relaxation of the cavernous smooth muscle. Both Rut-Caf and
      SNP determined dose-dependent relaxation with similar potency (pEC50) and maximum
      effect (E(max)). The substances showed activity through activation of the soluble
      guanylyl cyclase (sGC), because the relaxations were inhibited by ODQ.
      Oxyhemoglobin significantly diminished the relaxation effect of the substances. L
      cysteine failed to modify the relaxations caused by the agents. Hydroxicobalamine
      significantly diminished the relaxation effect of Rut-Caf. Glibenclamide
      significantly increased the efficacy of Rut-Caf (pEC50 4.09 x 7.09). There were
      no alterations of potency or maximum effect of the substances with the addition
      of the other ion channel blockers. Rut-Caf induced production of significant
      amounts of cGMP and cAMP during the relaxation process. CONCLUSIONS: In
      conclusion, Rut-Caf causes relaxation of smooth muscle of corpus cavernosum by
      means of activation of sGC with intracellular production of cGMP and cAMP; and
      also by release of NO in the intracellular environment. Rut-Caf releases the NO
      free radical and it does not act directly on the potassium ion channels.

PMID- 23131511
TI  - Umbilical KeyPort bilateral laparoscopic orchiectomy in patient with complete
      androgen insensitivity syndrome.
AB  - MAIN FINDINGS: A 22-year-old woman with complete androgen insensitivity syndrome
      (CAIS) presenting with primary amenorrhea and normal female external genitalia
      was referred for laparoscopic gonadectomy. She had been diagnosed several years
      earlier but was reluctant to undergo surgery. Case HYPOTHESIS: Diagnosis of this
      X-linked recessive inherited syndrome characterizes by disturbance of
      virilization in males with an AR mutation, XY karyotipe, female genitalia and
      severely undescended testis with risk of malignization. The optimal time to
      orchidectomy is not settled; neither the real risk of malignancy in these
      patients. Early surgery impacts development of a complete female phenotype, with
      enlargement of the breasts. Based on modern diagnostic imaging using DCE-MRI and
      surgical technology with single port laparoscopic access we hypothesize that the
      optimum time for gonadectomy is not at the time of diagnosis, but once
      feminization has completed. PROMISING FUTURE IMPLICATIONS: An umbilical
      laparoendoscopic single-site access for bilateral gonadectomy appears to be the
      first choice approach as leaves no visible incision and diminishes the
      psychological impact of surgery in a patient with CAIS absolutely reassured as
      female. KeyPort, a single port access with duo-rotate instruments developed by
      Richard Wolf facilitates this surgery and allows excellent cosmetic results.

PMID- 23131512
TI  - Sigmoid colon ureteral fistula presenting with urosepsis.

PMID- 23131513
TI  - Erosion of inferior vena caval filter noted during robotic assisted laparoscopic
      partial nephrectomy.
AB  - Inferior Vena Cava (IVC) filters are mechanical devices implanted to provide
      prophylaxis against pulmonary emboli in patients for whom standard
      anticoagulation is either inadequate or contraindicated. A 67-year-old female
      with a 10-year-old indwelling IVC filter underwent robotic assisted laparoscopic
      partial nephrectomy for a right upper pole renal mass. Renal hilum dissection was
      complicated by adhesions secondary to eroded IVC filter struts. IVC filter
      erosion is a well-described phoenomena in both the radiologic and surgical
      literature. As many as 25% of filters are noted to be radiographically eroded;
      however, the incidence of clinically significant erosion is much less. Given the
      placement of endovascularly delivered IVC filters in close proximity to many
      urologic operative fields, it is important for urologists to be aware of the
      potential of eroded devices when pursuing para-caval dissections.

PMID- 23131514
TI  - Urethral duplication II-A Y type with rectal urethra: ASTRA approach and tunica
      vaginalis flap for first stage repair.
AB  - INTRODUCTION: Urethral duplication is a rare congenital anomaly affecting mainly
      boys. Generally, the duplication develops on the sagittal plane; the accessory
      urethra may run dorsally or ventrally to the orthotopic one. We present a patient
      with urethral duplication in which the orthotopic urethra was patent in the
      penile segment but atresic in the bulbar and prostatic segment. The patient had
      urinary flow from the rectum and the ectopic urethra could be well identified by
      anal examination. MATERIALS AND METHODS: Age at surgery was 13 months. The
      procedure consisted of an ASTRA (anterior sagittal trans-ano-rectal) approach for
      dividing the urethra and rectum and was successful to move the urethra up to the
      perineal area. The rectum was reconstructed and the patient placed into a
      lithotomy position. A urethral catheter inserted in the penile urethra oriented
      us were the atresic urethra in bulbar area started. The scrotum was opened in the
      middle and the distance between the two urethral stumps proximal and distal
      defined the extension of no urethral tissue that consisted of 5 cm. We opened the
      right scrotal space and a tunica vaginalis flap was obtained and attached to the
      bulbar tissue for a two-stage urethroplasty strategy. RESULTS: Patient had a nice
      healing and the tunica vaginalis was nicely incorporated to the adjacent tissue,
      having the two urethral stumps well delineated. CONCLUSIONS: ASTRA approach in
      combination with a two-stage urethroplasty with tunica vaginalis dorsal flap
      proved to be an excellent combination for a rare case of urethral Y duplication
      having the main urethra into the rectum.

PMID- 23131516
TI  - Unexplained male infertility: diagnosis and management.
AB  - Unexplained male infertility is a diagnosis reserved for men in whom routine
      semen analyses results are within normal values and physical as well as endocrine
      abnormalities were ruled out. In addition to erectile problems and coital
      factors, immunologic causes and sperm dysfunction may contribute to such
      condition. New etiologies of unexplained male infertility include low level
      leukocytospermia and mitochondrial DNA polymerase gene polymorphism. Contemporary
      andrology may reveal cellular and sub-cellular sperm dysfunctions which may
      explain subfertility in such cases, thus aiding the clinician to direct the
      further work-up, diagnosis and counseling of the infertile male. The objective of
      this article is to highlight the concept of unexplained male infertility and
      focuses on the diagnosis and treatment of this condition in the era of modern
      andrology and assisted reproductive techniques. Extensive literature review was
      performed using the search engines: Pubmed, Science-direct, Ovid and Scopus.

PMID- 23131517
TI  - Cost-effectiveness analysis of medical treatment of benign prostatic hyperplasia
      in the Brazilian public health system.
AB  - OBJECTIVE: To perform a cost-effectiveness analysis of medical treatment of
      benign prostatic hyperplasia (BPH) under Brazilian public health system
      perspective (Unified Health System--"Sistema Unico de Saude (SUS)"). MATERIAL AND
      METHODS: A revision of the literature of the medical treatment of BPH using alpha
      blockers, 5-alpha-reductase inhibitors and combinations was carried out. A panel
      of specialists defined the use of public health resources during episodes of
      acute urinary retention (AUR), the treatment and the evolution of these patients
      in public hospitals. A model of economic analysis (Markov) predicted the number
      of episodes of AUR and surgeries (open prostatectomy and transurethral resection
      of the prostate) related to BPH according to stages of evolution of the disease.
      Brazilian currency was converted to American dollars according to the theory of
      Purchasing Power Parity (PPP 2010: US$ 1 = R$ 1.70). RESULTS: The use of
      finasteride reduced 59.6% of AUR episodes and 57.9% the need of surgery compared
      to placebo, in a period of six years and taking into account a treatment
      discontinuity rate of 34%. The mean cost of treatment was R$ 764.11 (US$ 449.78)
      and R$ 579.57 (US$ 340.92) per patient in the finasteride and placebo groups,
      respectively. The incremental cost-effectiveness ratio (ICERs) was R$ 4.130 (US$
      2.429) per episode of AUR avoided and R$ 2.735 (US$ 1.609) per episode of surgery
      avoided. The comparison of finasteride + doxazosine to placebo showed a reduction
      of 75.7% of AUR episodes and 66.8% of surgeries in a 4 year time horizon, with a
      ICERs of R$ 21.191 (US$ 12.918) per AUR episodes avoided and R$ 11.980 (US$
      7.047) per surgery avoided. In the sensitivity analysis the adhesion rate to
      treatment and the cost of finasteride were the main variables that influenced the
      results. CONCLUSIONS: These findings suggest that the treatment of BPH with
      finasteride is cost-effective compared to placebo in the Brazilian public health
      system perspective.

PMID- 23131518
TI  - Perioperative platelet inhibition in transurethral interventions: TURP/TURB.
AB  - PURPOSE: To determine whether transurethral surgery under platelet inhibition is
      a feasible procedure. Before transurethral resection of prostate (TURP) or
      bladder tumours (TURB), the administration of platelet-inhibiting medication is
      often interrupted due to possible bleeding complications. We studied the
      performance of TURP and TURB under the current recommendations of the American
      College of Chest Physicians (ACCP) on perioperative platelet inhibition.
      MATERIALS AND METHODS: Patients assigned for transurethral intervention were
      preoperatively divided into the following risk groups: low, medium and high
      cardio- or cerebrovascular risk. In patients with a low-risk profile,
      acetylsalicylic acid (ASA) was discontinued. Patients of the medium risk group
      continued taking 100 mg of ASA. Patients of the high-risk group receiving dual
      platelet inhibition (ASA + clopidogrel) were not treated operatively. In total
      346 patients from the low and medium risk groups underwent transurethral
      intervention. RESULTS: Forty-two out of 198 TURP were performed under 100 mg of
      ASA. Without ASA, a significantly shorter length of stay and earlier removal of
      the transurethral catheter was documented. In the parameters postoperative
      haemorrhage and operative revision, no significant differences were observed.
      Thirty-two out of 148 TURB were performed under 100 mg of ASA. Regarding the
      length of stay, time until catheter removal, postoperative haemorrhage and
      operative revision, no significant differences were found under ASA. Only
      significantly longer continuous irrigation was documented under ASA. CONCLUSION:
      In the case of a verified indication for use of platelet inhibitors, it is
      possible to avoid discontinuation and the consequent increased risk of
      thromboembolic incidents in transurethral surgery is admissible.

PMID- 23131519
TI  - Second to fourth digit ratio: its relationship with core cancer volume and
      Gleason score in prostate biopsy.
AB  - OBJECTIVE: To investigate the relationships between 2nd to 4th digit ratio (digit
      ratio) and prostate cancer detection rate and biopsy findings, including Gleason
      score. MATERIALS AND METHODS: In 770 consecutive men aged 40 years or older that
      presented with lower urinary tract symptoms (LUTS), right hand 2nd and 4th digit
      lengths were measured prior to PSA determinations, DRE and transrectal
      ultrasonography (TRUS). Among these, 166 men with a prostate specific antigen
      (PSA) level >= 3 ng/mL or abnormal digit rectal examination (DRE) prospectively
      underwent prostate biopsies. The relationship between digit ratio and prostate
      cancer detection rate and biopsy findings was investigated. RESULTS: The study
      subjects were allocated to two groups by digit ratio (group A: digit ratio <
      0.95; n = 420; group B: digit ratio >= 0.95; n = 350). Despite similar biopsy
      rates (22.4% vs. 20.6%, p = 0.544), group A had higher cancer detection rate
      (46.8% (44/94) vs. 23.6% (17/72), p = 0.002; OR = 2.847, 95% CI = 1.445-5.610).
      When we analyzed 408 positive biopsy cores (group A: digit ratio < 0.95, n = 282;
      group B: digit ratio >= 0.95, n = 126), group A had higher percentage of core
      cancer volume (46.7% vs. 37.1%, p = 0.005) and more biopsy cores with high
      Gleason score (sum of Gleason score >= 9: 18/282 (6.4%) vs. 1/126 (0.8%), p =
      0.010; primary Gleason score = 5: 12/282 (4.3%) vs. 0/126 (0.0%), p = 0.021).
      CONCLUSIONS: A lower digit ratio is related to an increased detection rate of
      prostate cancer, a high percentage of core cancer volume and a high Gleason
      score.

PMID- 23131520
TI  - The accuracy of multidetector Computed Tomography for preoperative staging of
      renal cell carcinoma.
AB  - PURPOSE: The purpose of this study was to evaluate the accuracy of multidetector
      computed tomography (MDCT) in the preoperative staging of renal cell carcinoma
      (RCC). MATERIALS AND METHODS: We retrospectively reviewed the clinical and
      pathological records of 312 patients with RCC who underwent staging MDCT before
      surgery. Radiographic findings were compared to the findings at surgery and
      pathological examination. All staging used 2009 updated TNM classification.
      RESULTS: The difference in tumor size between radiographic and pathological
      findings was 0.21 cm. In T1a group, the difference was 0.33 cm. Agreement between
      MDCT and histopathological findings was moderate for T staging (Kappa = 0.469),
      fair for N staging (Kappa = 0.322), and excellent for M staging (Kappa = 0.932).
      The sensitivity and specificity of MDCT in detecting perinephric fat invasion
      were 32.26% and 85.87%, in detecting tumor thrombosis were 84% and 100%, in
      detecting adrenal gland invasion were 60% and 95.79%, in detecting lymph node
      involvement were 50% and 96.36%, in detecting distant metastasis were 100% and
      99.67%, respectively. In regard to stage grouping, 237 of 314 patients were
      correctly staged by MDCT, with an overall accuracy of 75.48%. CONCLUSIONS: MDCT
      with a dynamic contrast protocol is able to delineate RCC with high accuracy.
      However, a great portion of tumors were overstaged by MDCT because of
      overestimation of tumor size and poor visualization of infiltration of the
      perinephric fat. In addition, nodal metastatic lesion evaluation relies on node
      size only and remains a difficult task.

PMID- 23131521
TI  - Cystectomy and urinary diversion in the treatment of bladder cancer without
      artificial respiration.
AB  - PURPOSE: To assess the feasibility and performance of radical cystectomy with
      urinary diversion using exclusively regional anesthesia (i.e. combined spinal
      thoracic epidural anesthesia, CSTEA). MATERIALS AND METHODS: In 2011 radical
      cystectomy with extended pelvic and iliac lymphadenectomy was performed on 14
      patients using urinary diversion without applying general anesthesia. Under
      maintained spontaneous breathing, the patients were awake and responsive during
      the entire procedure. Postoperatively, pain management took three days with the
      remaining epidural catheter before oral analgesics were administered.
      Mobilization and diet restoration were carried out according to the fast-track
      concept. Outcome measurements included operative time, blood loss, beginning of
      oral nutrition, beginning of mobilization, postoperative pain levels using
      numerical and visual analog scales (NAS/VAS), length of hospital stay. RESULTS:
      All surgical procedures were performed without any complications. The absence of
      general anesthesia did not result in any relevant disadvantages. The
      postoperative progress was normal in all patients. Particularly, cardiopulmonary
      complications and enteroparesis did not occur. The provided palliative care
      proved sufficient (NAS max. 3-4). Discharge followed 10 to 22 days after surgery.
      At the time of discharge, the patients described the procedure to be relatively
      positive. CONCLUSIONS: Our data show that CSTEA is an effective technique for
      radical cystectomy, whereby spontaneous breathing and reduced interference with
      the cardiopulmonary system potentially lower the perioperative risks especially
      for high-risk patients. We recommend practice of CSTEA for radical cystectomy to
      further evaluate and monitor the safety, efficacy, outcomes, and complications of
      CSTEA.

PMID- 23131522
TI  - Detrusor overactivity in diabetic and non-diabetic patients: is there a
      difference?
AB  - PURPOSE: To compare urodynamic characteristics in patients with idiopathic
      detrusor overactivity (IDO) with those of an age matched cohort with diabetes
      mellitus (DM) and detrusor overactivity (DO). Secondly, to determine whether
      urodynamic features could help distinguish these two groups of patients.
      MATERIALS AND METHODS: Urodynamic data was collected on 58 female patients; 29
      with IDO and 29 with DM and detrusor overactivity. Eight urodynamic parameters
      were selected for analysis: amplitude of the first overactive contraction (AOFC),
      the volume at the first contraction, cystometric capacity, maximal detrusor
      pressure, maximal flow rate, voiding pressure at maximal flow, voided volume and
      postvoid residual (PVR) urine volume. Finally, sensitivity analysis for
      distinguishing urodynamic parameters between studied groups was performed.
      RESULTS: AOFC, volume at AOFC and maximal detrusor pressure were statistically
      greater in diabetic patients, compared with the non-diabetic group of women
      (16.00 cm H2O versus 9.00 cm H2O, 309.00 mL versus 167.00 mL and 76.48 cm H2O
      versus 55.41 cm H2O respectively). A specificity of 72.41% and positive
      predictive value of 71.43% were achieved for AOFC with cutoff value of 12 cm H2O.
      These parameters were further improved with cutoff value of 258 mL for volume at
      AOFC and were 75.86% and 73.08% respectively. CONCLUSIONS: Certain urodynamic
      parameters in diabetic female patients with DO are shown to be significantly
      different than those in women with IDO. Further prospective study should provide
      additional information about the pathogenesis and progression of DO in diabetic
      patients as well as the validity of diabetic screening in patients with IDO.

PMID- 23131523
TI  - Induced pluripotent stem cells: from Nobel Prizes to clinical applications.
AB  - Advances in basic hepatology have been constrained for many years by the
      inability to culture primary hepatocytes in vitro, until just over five years ago
      when the scientific playing field was changed beyond recognition with the
      demonstration that human skin fibroblasts could be reprogrammed to resemble
      embryonic cells. The reprogrammed cells, known as induced pluripotent stem cells
      (iPSCs), were then shown to have the capacity to re-differentiate into almost any
      human cell type, including hepatocytes. The unlimited number and isogenic nature
      of the cells that can be generated from tiny fragments of tissue have massive
      implications for the study of human liver diseases in vitro. Of more immediate
      clinical importance were recent data demonstrating precision gene therapy on
      patient specific iPSCs, which opens up the real and exciting possibility of
      autologous hepatocyte transplantation as a substitute for allogeneic whole liver
      transplantation, which has been an effective approach to end-stage liver disease,
      but one that has now been outstripped by demand. In this review, we describe the
      historical development, current technology and potential clinical applications of
      induced pluripotency, concluding with a perspective on possible future directions
      in this dynamic field.

PMID- 23131524
TI  - Association of small vessel ischemic white matter changes with BOLD fMRI imaging
      in the elderly.
AB  - White matter hyperintensities (WMHs) are often identified on T2-weighted magnetic
      resonance (MR) images in the elderly. The WMHs are generally associated with
      small vessel ischemic or pre-ischemic changes. However, the association of WMHs
      with blood oxygen level dependent (BOLD) functional magnetic resonance imaging
      (fMRI) signal is understudied. In this study, we evaluate how the BOLD signal
      change is related to the presence of WMHs in the elderly. Data were acquired as
      part of a study of late-life depression and included elderly individuals with and
      without major depression. The subjects were pooled because the presence of
      depression was not significantly associated with task-related BOLD changes, task
      performance, and WMH distribution. A whole brain voxel-wise regression analysis
      revealed a significant negative correlation between WMH burden and BOLD signal
      change during finger-tapping in the parietal white matter. Our observation that
      WMHs are associated with a significant diminution of the BOLD signal change
      underscores the importance of considering cerebrovascular burden when
      interpreting fMRI studies in the elderly. The mechanism underlying the
      association of WMH and BOLD signal change remains unclear: the association may be
      mediated by changes in neural activation, changes in coupling between neuronal
      activity and hemodynamics, or, perhaps, secondary to the effect of the ischemic
      changes on the sensitivity of the T2* BOLD MR signal.

PMID- 23131525
TI  - Neural correlates of affective priming effects based on masked facial emotion: an
      fMRI study.
AB  - Affective priming refers to the phenomenon that subliminal presentation of facial
      emotion biases subsequent evaluation of a neutral object in the direction of the
      prime. The aim of the present study was to specify the neural correlates of
      evaluative shifts elicited by facial emotion shown below the threshold of
      conscious perception. We tested the hypotheses whether the amygdala is involved
      in negative priming, whereas the nucleus accumbens participates in positive
      priming. In addition, exploratory whole brain correlation analyses were
      conducted. During 3T fMRI scanning, pictures of sad, happy, and neutral facial
      expression masked by neutral faces were presented to 110 healthy adults who had
      to judge valence of masks on a four-point scale. There was evidence for
      significant negative priming based on sad faces. A correlation was observed
      between amygdala activation and negative priming. Activation in medial, middle,
      and superior frontal and middle temporo-occipital areas, and insula was also
      associated with negative priming. No significant priming based on happy faces was
      found. However, nucleus accumbens activation to happy faces correlated with the
      positive priming score. The present findings confirm that the amygdala but also
      other brain regions, especially the medial frontal cortex, appear involved in
      automatically elicited negative evaluative shifts.

PMID- 23131526
TI  - Acute aquatic treadmill exercise improves gait and pain in people with knee
      osteoarthritis.
AB  - OBJECTIVE: To examine the acute effects of aquatic and land treadmill exercise on
      gait kinematics as well as the level of disease-specific and movement-related
      pain for individuals with osteoarthritis. DESIGN: Quasi-experimental crossover
      design. SETTING: Biomechanics laboratory. PARTICIPANTS: Participants (N=14; age,
      43-64y) diagnosed with osteoarthritis at the knee (n=12), osteoarthritis at the
      knee and ankle (n=1), or osteoarthritis at the knee and hip (n=1). INTERVENTIONS:
      Participants performed 3 exercise sessions separated by at least 24 hours in 1
      week for each mode of exercise (aquatic treadmill and land treadmill). MAIN
      OUTCOME MEASURES: Gait kinematics and pain were measured before and after each
      intervention. RESULTS: The angular velocity gain score during stance for left
      knee extension was improved by 38% after aquatic treadmill exercise (P=.004).
      Similarly, during swing, the gain scores for angular velocity were also greater
      for left knee internal rotation and extension by 65% and 20%, respectively
      (P=.004, P=.008, respectively). During stance, the joint angle gain score for
      left hip flexion was 7.23% greater after land exercise (P=.007). During swing,
      the angular velocity gain score for right hip extension was significantly greater
      for aquatic exercise by 28% (P=.01). Only the joint angle gain score for left
      ankle abduction during stance was significantly higher after land exercise
      (4.72%, P=.003). No other joint angle gain scores for either stance or swing were
      significantly different for either condition (P=.06-.96). Perceived pain was 100%
      greater after land than aquatic treadmill exercise (P=.02). Step rate and step
      length were not different between conditions (P=.31-.92). CONCLUSIONS: An acute
      training period on an aquatic treadmill positively influenced joint angular
      velocity and arthritis-related joint pain. Acute aquatic treadmill exercise may
      be useful as a conservative treatment to improve angular speed of the lower
      extremity joints and pain related to osteoarthritis.

PMID- 23131528
TI  - An exercise therapy program can increase oxygenation and blood volume of the
      erector spinae muscle during exercise in chronic low back pain patients.
AB  - OBJECTIVE: To determine whether erector spinae muscle oxygenation (OXY) and blood
      volume during a progressive isoinertial lifting evaluation (PILE) are modified by
      an exercise therapy program. DESIGN: Pre- (t1) and post- (t2) exercise therapy
      experimental design. SETTING: Hospital. PARTICIPANTS: Subjects with chronic low
      back pain (LBP group) (n=24) and healthy subjects (control group) (n=24) were
      evaluated. INTERVENTION: Exercise program. MAIN OUTCOME MEASURES: The control
      group was evaluated once, and the LBP group was evaluated before (t1) the
      exercise therapy program and 28 days thereafter (t2). The maximal load lifted,
      total work, and total power were determined using the PILE test. Continuous-wave
      near-infrared spectroscopy was used to measure OXY and blood volume during the
      PILE test. RESULTS: The maximal load lifted, total power, and total work were
      significantly lower in the LBP group (-42%+/-5%, -46%+/-6%, and -67%+/-6% at t1,
      respectively; P<.05) than the control group. In the LBP subjects, these
      parameters improved significantly after the exercise therapy program (+20%+/-3%,
      +56%+/-4%, and +61%+/-5%; P<.05). At each submaximal power (ie, 25, 50, 75, and
      100% of maximal load lifted at t1), OXY and blood volume were significantly
      higher at t2 than t1. One-half recovery time for OXY was significantly higher in
      the LBP group (at t1 and t2) than in control subjects. CONCLUSIONS: The findings
      in this study suggest that LBP subjects present an impairment in their capacity
      to deliver oxygen at the level of the erector spinae muscle, which can be partly
      restored by an exercise therapy program.

PMID- 23131527
TI  - Association of parent ratings of executive function with global- and setting
      specific behavioral impairment after adolescent traumatic brain injury.
AB  - OBJECTIVE: To determine the association of primary caregiver-rated behavioral and
      metacognitive aspects of executive function (EF) with impaired functioning after
      adolescent traumatic brain injury (TBI). DESIGN: Multicenter cross-sectional
      study. SETTING: Outpatient. PARTICIPANTS: Primary caregivers and children (N=132)
      aged 12 to 17 years who sustained a moderate or severe TBI within the past 1 to 6
      months. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Primary caregiver
      ratings of EF, tests of memory and processing speed (PS), and a structured parent
      interview to assess clinical impairments in behavioral functioning were used.
      Logistic regression was used to examine the relation of ratings of EF with
      clinical ratings of impairment in global adolescent functioning and in
      functioning in the home, school, and community settings after controlling for
      sex, race, socioeconomic status, injury severity, and performance on the tests of
      memory and PS. RESULTS: Caregiver ratings of poor EF were associated with
      impairment in both global behavioral functioning (odds ratio [OR]=4.73; 95%
      confidence interval [CI], 1.54-14.52; P<.01) and community functioning (OR=13.28;
      95% CI, 1.94-90.87; P<.01). CONCLUSIONS: Caregiver ratings of deficits in EF were
      associated with impaired behavioral functioning after adolescent TBI and were
      independent of performance on tests of memory and processing speed. Understanding
      the relation of EF with clinical impairments as manifested in different settings
      will help hone assessment batteries and focus treatments where they are needed
      most.

PMID- 23131529
TI  - Prenatal management of disorders of sex development.
AB  - Disorders of sex development (DSD) rarely present prenatally but, as they are
      very complex conditions, management should be directed by highly specialised
      medical teams to allow consideration of all aspects of diagnosis, treatment and
      ethical issues. In this brief review, we present an overview of the prenatal
      presentation and management of DSD, including the sonographic appearance of
      normal genitalia and methods of determining genetic sex, the prenatal management
      of pregnancies with the unexpected finding of genital ambiguity on prenatal
      ultrasound and a review of the prenatal management of pregnancies at high risk of
      DSD. As this is a rapidly developing field, management options will change over
      time, making the involvement of clinical geneticists, paediatric endocrinologists
      and urologists, as well as fetal medicine specialists, essential in the care of
      these complex pregnancies. The reader should also bear in mind that local social,
      ethical and legal aspects may also influence management.

PMID- 23131530
TI  - Does hydrochlorothiazide prevent recurrent urinary tract infection in children
      with idiopathic hypercalciuria?
AB  - OBJECTIVE: Idiopathic hypercalciuria (IHC) has been recognized as a common
      disorder in childhood, and is a major factor in the formation of renal stones and
      urinary tract infections (UTIs). Since hydrochlorothiazide ameliorates
      hypercalciuria, we assessed its efficacy in preventing recurrent UTIs in
      hypercalciuric girls. MATERIALS AND METHODS: This research was a single blind
      randomized clinical trial. One hundred 1-12-year-old girls, who were followed in
      pediatric nephrology outpatient clinics of two referral hospitals in Markazi
      Province of Iran, were recruited. All patients had IHC and at least two UTIs in 1
      year, without any underlying anatomic or functional abnormality of urinary tract.
      Patients were randomly divided into two equal groups. One group received
      instructions regarding general preventive measures for UTI and the other group,
      in addition to these measures, received 1 mg/kg/day hydrochlorothiazide as
      morning dose. Then recurrence of UTI in the two groups was evaluated. RESULTS:
      The mean age was 7.28 +/- 1.9 years. In both groups, the incidence of UTI
      recurrence was 66%. CONCLUSION: On the basis of these results, we reject the
      hypothesis that treating hypercalciuria is beneficial in preventing repeated
      UTIs. The association between UTIs and IHC needs to be more closely studied and
      attention to eliminating confounding factors is necessary.

PMID- 23131531
TI  - The importance of microstructural variations on the fracture toughness of human
      dentin.
AB  - The crack growth resistance of human dentin was characterized as a function of
      relative distance from the DEJ and the corresponding microstructure. Compact
      tension specimens were prepared from the coronal dentin of caries-free 3rd
      molars. The specimens were sectioned from either the outer, middle or inner
      dentin. Stable crack extension was achieved under Mode I quasi-static loading,
      with the crack oriented in-plane with the tubules, and the crack growth
      resistance was characterized in terms of the initiation (K(o)), growth (K(g)) and
      plateau (K(p)) toughness. A hybrid approach was also used to quantify the
      contribution of dominant mechanisms to the overall toughness. Results showed that
      human dentin exhibits increasing crack growth resistance with crack extension in
      all regions, and that the fracture toughness of inner dentin (2.2 +/- 0.5
      MPa.m(0.5)) was significantly lower than that of middle (2.7 +/- 0.2 MPa.m(0.5))
      and outer regions (3.4 +/- 0.3 MPa.m(0.5)). Extrinsic toughening, composed mostly
      of crack bridging, was estimated to cause an average increase in the fracture
      energy of 26% in all three regions. Based on these findings, dental restorations
      extended into deep dentin are much more likely to cause tooth fracture due to the
      greater potential for introduction of flaws and decrease in fracture toughness
      with depth.

PMID- 23131533
TI  - The cellular uptake and localization of non-emissive iridium(III) complexes as
      cellular reaction-based luminescence probes.
AB  - Improvement of cellular uptake and subcellular resolution remains a major
      obstacle in the successful and broad application of cellular optical probes. In
      this context, we design and synthesize seven non-emissive cyclometalated
      iridium(III) solvent complexes [Ir(C^N)(2)(solv)(2)](+)L(-) (LIr2-LIr8, in which
      C^N = 2-phenylpyridine (ppy) or its derivative; solv = DMSO, H(2)O or CH(3)CN; L(
      ) = PF(6)(-) or OTf(-)) applicable in live cell imaging to facilitate selective
      visualization of cellular structures. Based on the above variations (including
      different counter ions, solvent ligands, and C^N ligands), structure-activity
      relationship analyses reveal a number of clear correlations: (1) variations in
      counter anions and solvent ligands of iridium(III) complexes do not affect
      cellular imaging behavior, and (2) length of the side carbon chain in C^N ligands
      has significant effects on cellular uptake and localization/accumulation of
      iridium complexes in living cells. Moreover, investigation of the uptake
      mechanism via low-temperature and metabolism inhibitor assays reveal that [Ir(4
      Meppy)(2)(CH(3)CN)(2)](+)OTf(-) (LIr5) with 2-phenylpyridine derivative with side
      chain of methyl group at the 4-position as C^N ligand permeates the outer and
      nuclear membranes of living cells through an energy-dependent, non-endocytic
      entry pathway, and translocation of the complex from the cell periphery towards
      the perinuclear region possibly occurs through a microtubule-dependent transport
      pathway. Nuclear pore complexes (NPCs) appear to selectively control the
      transport of iridium(III) complexes between the cytoplasm and nucleus. A
      generalization of trends in behavior and structure-activity relationships is
      presented, which should provide further insights into the design and optimization
      of future probes.

PMID- 23131532
TI  - Engineering cell-material interfaces for long-term expansion of human pluripotent
      stem cells.
AB  - Cost-effective and scalable synthetic matrices that support long-term expansion
      of human pluripotent stem cells (hPSCs) have many applications, ranging from drug
      screening platforms to regenerative medicine. Here, we report the development of
      a hydrogel-based matrix containing synthetic heparin-mimicking moieties that
      supports the long-term expansion of hPSCs (>=20 passages) in a chemically defined
      medium. HPSCs expanded on this synthetic matrix maintained their characteristic
      morphology, colony forming ability, karyotypic stability, and differentiation
      potential. We also used the synthetic matrix as a platform to investigate the
      effects of various physicochemical properties of the extracellular environment on
      the adhesion, growth, and self-renewal of hPSCs. The observed cellular responses
      can be explained in terms of matrix interface-mediated binding of extracellular
      matrix proteins, growth factors, and other cell-secreted factors, which create an
      instructive microenvironment to support self-renewal of hPSCs. These synthetic
      matrices, which comprise of "off-the-shelf" components and are easy to
      synthesize, provide an ideal tool to elucidate the molecular mechanisms that
      control stem cell fate.

PMID- 23131534
TI  - The spatial and temporal control of cell migration by nanoporous surfaces through
      the regulation of ERK and integrins in fibroblasts.
AB  - Nanotopography controls cell behaviours, such as cell adhesion and migration.
      However, the mechanisms responsible for topology-mediated cellular functions are
      not fully understood. A variety of nanopores was fabricated on 316L stainless
      steel to investigate the effects of spatial control on the growth and function of
      fibroblasts, the temporal regulation of integrins, and their effects on
      migration. The NIH-3T3 fibroblast cell line was cultured on the nanopore
      surfaces, whose pore diameters ranged from 40 to 210 nm. The 40 and 75 nm
      nanopores enhanced cell proliferation, focal adhesion formation and protein
      expression of vinculin and beta-tubulin after 24 h of incubation. Integrin
      expression was analysed by qPCR, which showed the extent of spatial and temporal
      regulation achieved by the nanopores. The protein expression of pERK1/2 was
      greatly attenuated in cells grown on 185 and 210 nm nanopore surfaces at 12 and
      24 h. In summary, the 40 and 75 nm nanopore surfaces promoted cell adhesion and
      migration in fibroblasts by controlling the temporal expression of integrins and
      ERK1/2. The current study provides insight into the improvement of the design of
      stainless steel implants and parameters that affect biocompatibility. The ability
      to regulate the expression of integrin and ERK1/2 using nanopore surfaces could
      lead to further applications of surface modification in the fields of
      biomaterials science and tissue engineering.

PMID- 23131535
TI  - Neurite outgrowth and synaptophysin expression of postnatal CNS neurons on GaP
      nanowire arrays in long-term retinal cell culture.
AB  - We have established long-term cultures of postnatal retinal cells on arrays of
      gallium phosphide nanowires of different geometries. Rod and cone photoreceptors,
      ganglion cells and bipolar cells survived on the substrates for at least 18 days
      in vitro. Glial cells were also observed, but these did not overgrow the neuronal
      population. On nanowires, neurons extended numerous long and branched neurites
      that expressed the synaptic vesicle marker synaptophysin. The longest nanowires
      (4 MUm long) allowed a greater attachment and neurite elongation and our analysis
      suggests that the length of the nanowire per se and/or the adsorption of
      biomolecules on the nanowires may have been important factors regulating the
      observed cell behavior. The study thus shows that CNS neurons are amenable to
      gallium phosphide nanowires, probably as they create conditions that more closely
      resemble those encountered in the in vivo environment. These findings suggest
      that gallium phosphide nanowires may be considered as a material of interest when
      improving existing or designing the next generation of implantable devices. The
      features of gallium phosphide nanowires can be precisely controlled, making them
      suitable for this purpose.

PMID- 23131537
TI  - Animal personalities matter for biological invasions.

PMID- 23131536
TI  - Incorporation of paramagnetic, fluorescent and PET/SPECT contrast agents into
      liposomes for multimodal imaging.
AB  - A series of metal-chelating lipid conjugates has been designed and synthesized.
      Each member of the series bears a 1,4,7,10-tetraazacyclododecane-1,4,7,10
      tetraacetic acid (DOTA) macrocycle attached to the lipid head group, using short
      n-ethylene glycol (n-EG) spacers of varying length. Liposomes incorporating these
      lipids, chelated to Gd(3+), (64)Cu(2+), or (111)In(3+), and also incorporating
      fluorescent lipids, have been prepared, and their application in optical,
      magnetic resonance (MR) and single-photon emission tomography (SPECT) imaging of
      cellular uptake and distribution investigated in vitro and in vivo. We have shown
      that these multimodal liposomes can be used as functional MR contrast agents as
      well as radionuclide tracers for SPECT, and that they can be optimized for each
      application. When shielded liposomes were formulated incorporating 50% of a lipid
      with a short n-EG spacer, to give nanoparticles with a shallow but even coverage
      of n-EG, they showed good cellular internalization in a range of tumour cells,
      compared to the limited cellular uptake of conventional shielded liposomes
      formulated with 7% 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N
      [carboxy(polyethyleneglycol)(2000)] (DSPE-PEG2000). Moreover, by matching the
      depth of n-EG coverage to the length of the n-EG spacers of the DOTA lipids, we
      have shown that similar distributions and blood half lives to DSPE-PEG2000
      stabilized liposomes can be achieved. The ability to tune the imaging properties
      and distribution of these liposomes allows for the future development of a
      flexible tri-modal imaging agent.

PMID- 23131540
TI  - Risk scores and prognostic models in surgery: pancreas resection as a paradigm.

PMID- 23131541
TI  - Synthesis, in silico, in vitro, and in vivo investigation of 5-[11C]methoxy
      substituted sunitinib, a tyrosine kinase inhibitor of VEGFR-2.
AB  - Sunitinib (SU11248) is a highly potent tyrosine kinase inhibitor targeting
      vascular endothelial growth factor receptor (VEGFR). Radiolabeled inhibitors of
      receptor tyrosine kinases (RTKs) might be useful tools for monitoring RTKs levels
      in tumor tissue giving valuable information for anti-angiogenic therapy. Herein
      we report the synthesis of 5-methoxy-sunitinib 5 and its (11)C-radiolabeled
      analog [(11)C]-5. The non-radioactive reference compound 5 was prepared by
      Knoevenagel condensation of 5-methoxy-2-oxindole with the corresponding
      substituted 5-formyl-1H-pyrrole. A binding constant (K(d)) of 20 nM for 5 was
      determined by competition binding assay against VEGFR-2. In addition, the binding
      mode of sunitinib and its 5-methoxy substituted derivative was studied by
      flexible docking simulations. These studies revealed that the substitution of the
      fluorine at position 5 of the oxindole scaffold by a methoxy group did not affect
      the inhibitor orientation, but affected the electrostatic and van der Waals
      interactions of the ligand with residues near the DFG motif of VEGFR-2. 5
      [(11)C]methoxy-sunitinib ([(11)C]-5) was synthesized by reaction of the desmethyl
      precursor with [(11)C]CH(3)I in the presence of DMF and NaOH in 17 +/- 3% decay
      corrected radiochemical yield at a specific activity of 162-205 GBq/MUmol (EOS).
      In vivo stability studies of [(11)C]-5 in rat blood showed that more than 70% of
      the injected compound was in blood stream, 60 min after administration.

PMID- 23131542
TI  - Improving the solubility of a new class of antiinflammatory pharmacodynamic
      hybrids, that release nitric oxide and inhibit cycloxygenase-2 isoenzyme.
AB  - The development of a novel class of pharmacodynamic hybrids that inhibits COX-2
      isoform is reported. These molecules display enhanced nitric oxide releasing
      properties due to the presence of an ionisable moiety. The in vivo analgesic/anti
      inflammatory activity was maintained in relation to the parent compounds.

PMID- 23131543
TI  - Involvement of neurotransmitters in the action of apelin-13 on passive avoidance
      learning in mice.
AB  - The widespread distribution of apelin-13 and apelin receptors in the brain
      suggests an important function of this neuropeptide in the brain that has not
      been explored extensively so far. In the present work, apelin-13 was found to
      facilitate the consolidation of passive avoidance learning in mice. In order to
      assess the possible involvement of transmitters in this action, the animals were
      pretreated with the following receptor blockers in doses which themselves did not
      influence the behavioral paradigm: phenoxybenzamine (a nonselective alpha
      adrenergic receptor antagonist), propranolol (a beta-adrenergic receptor
      antagonist), cyproheptadine (a nonselective 5-HT2 serotonergic receptor
      antagonist), atropine (a nonselective muscarinic acetylcholine receptor
      antagonist), haloperidol (a D2, D3 and D4 dopamine receptor antagonist),
      bicuculline (a gamma-aminobutyric acid subunit A (GABA-A) receptor antagonist),
      naloxone (a nonselective opioid receptor antagonist), and nitro-L-arginine (a
      nitric oxide synthase inhibitor). Phenoxybenzamine, cyproheptadine, atropine,
      haloperidol, bicuculline and nitro-L-arginine prevented the action of apelin-13.
      Propranolol and naloxone were ineffective. The data suggest that apelin-13
      elicits its action on the consolidation of passive avoidance learning via alpha
      adrenergic, 5-HT2 serotonergic, cholinergic, dopaminergic, GABA-A-ergic and
      nitric oxide mediations.

PMID- 23131544
TI  - Bifid mandibular condyle.
AB  - A 20-year-old young male patient presented with limited mouth opening and
      cosmetic disfigurement since childhood. On examination, marked mandibular
      hypoplasia resulting in a convex facial profile was noted. Further radiographic
      investigation using orthopantomograph and CT scan with three-dimensional
      reconstruction revealed bifid mandibular condyle of the right side.

PMID- 23131545
TI  - Solid-state NMR: a powerful tool for characterization of metal-organic
      frameworks.
AB  - Metal-organic frameworks (MOFs) are a new type of porous materials with numerous
      current and potential applications in many areas including ion-exchange,
      catalysis, sensing, separation, molecular recognition, drug delivery and, in
      particular, gas storage. Solid-state NMR (SSNMR) has played a pivotal role in
      structural characterization and understanding of host-guest interactions in MOFs.
      This article provides an overview on application of SSNMR to MOF systems.

PMID- 23131546
TI  - Perspective: Protein and exercise for frailty and sarcopenia: still learning.

PMID- 23131547
TI  - Perspective: Dietary protein needs of elderly people: protein supplementation as
      an effective strategy to counteract sarcopenia.

PMID- 23131548
TI  - Sarcopenia: what's in a name?

PMID- 23131549
TI  - Cryptic Onchocerca species infecting North American cervids, with implications
      for the evolutionary history of host associations in Onchocerca.
AB  - Parasites in the genus Onchocerca infect humans, ruminants, camels, horses,
      suids, and canids, with effects ranging from relatively benign to debilitating.
      In North America, Onchocerca cervipedis is the sole species known to infect
      cervids, while at least 5 Onchocerca species infect Eurasian cervids. In this
      study, we report the discovery of a cervid-parasitizing Onchocerca only distantly
      related to O. cervipedis. To reconstruct the phylogenetic history of the genus
      Onchocerca, we used newly acquired DNA sequence from O. cervipedis (from moose in
      Northwest Territories, Canada) and from the newly discovered species (from white
      tailed deer in upstate New York), as well as previously published sequences.
      Ancestral host reconstructions suggest that host switches have been common
      throughout the evolutionary history of Onchocerca, and that bovid- and cervid
      parasitizing species have been particularly important sources of descendant
      species. North America cervids might therefore serve as a source for Onchocerca
      invasions into new hosts. Given the high density of deer populations, the
      potential for zoonotic infections may also exist. Our discovery of a new
      Onchocerca species with relatively limited sampling suggests that the diversity
      of Onchocerca associated with cervids in North America may be greater than
      previously thought, and surveys utilizing molecules and morphology are necessary.

PMID- 23131550
TI  - SUMOylation negatively regulates the stability of CHFR tumor suppressor.
AB  - CHFR ubiquitin ligase acts as a checkpoint upon DNA damage and its functional
      inactivation is one of key characteristics of tumor development and metastasis.
      Despite the crucial role in maintaining genome integrity and cell cycle
      progression, little is known how CHFR stability is regulated. Here, we showed
      that CHFR is covalently modified by SUMO-1 at lysine 663 and subsequently
      destabilized by ubiquitin-proteasome system. While CHFR(K663R) substitution
      mutation does not alter its subcellular localization, SUMOylation-defective
      CHFR(K663R)-stable cells exhibit substantial growth suppression due to the
      increased stability of CHFR(K663R). Moreover, protein level of CHFR, not
      CHFR(K663R), is rapidly declined under SUMOylation-promoting conditions, and
      SENP2 deSUMOylating enzyme reverses its SUMO-modification. Collectively, we
      demonstrated that CHFR stability is regulated by SUMOylation-dependent
      proteasomal degradation. Therefore, our study underscores the importance of CHFR
      SUMOylation as a new regulatory mechanism of CHFR and highlights the emerging
      role of SUMOylation in modulating protein stability.

PMID- 23131551
TI  - Ribosomal protein S3 localizes on the mitotic spindle and functions as a
      microtubule associated protein in mitosis.
AB  - The human ribosomal protein S3 (rpS3) has multi-functions such as translation,
      DNA repair and apoptosis. These multiple functions are regulated by post
      translational modifications including phosphorylation, methylation and
      sumoylation. We report here a novel function of rpS3 that is involved in mitosis.
      When we examined localization of ribosomal proteins in mitosis, we found that
      rpS3 specifically localizes on the mitotic spindle. Depletion of the rpS3
      proteins caused mitotic arrest during the metaphase. Furthermore, the shape of
      the spindle and chromosome movement in the rpS3 depleted cell was abnormal.
      Microtubule (MT) polymerization also decreased in rpS3 depleted cells, suggesting
      that rpS3 is involved in spindle dynamics. Therefore, we concluded that rpS3 acts
      as a microtubule associated protein (MAP) and regulates spindle dynamics during
      mitosis.

PMID- 23131552
TI  - ANKRD18A as a novel epigenetic regulation gene in lung cancer.
AB  - Lung cancer is one of the most common causes of cancer-related mortality
      worldwide. Effective early diagnosis and targeted therapies for lung cancer to
      reduce incidence and mortality would benefit from a better understanding of the
      key molecular changes that occur from normal to malignant tumor cells during lung
      cancer initiation and development, but these are largely unknown. Previous
      studies have shown that DNA methylation, an important mechanism for the
      regulation of gene expression, plays a key role in lung carcinogenesis. In this
      study, we screened a novel methylation gene, ANKRD18A, encoding ankyrin repeat
      domain 18A, to determine whether it is regulated by DNA methylation in lung
      cancer. Methylation-specific PCR and bisulfite sequencing PCR were used to
      analyze gene methylation status, and real-time quantitative reverse transcription
      polymerase chain reaction (qRT-PCR) examined mRNA levels. Promoter
      hypermethylation of ANKRD18A was detected in 68.4% (26/38) of lung cancer tissues
      but not (0/20) in normal lung tissues (P<0.01), whereas ANKRD18A mRNA expression
      was significantly decreased in lung cancer tissues compared with adjacent normal
      tissues. In addition, we found that ANKRD18A expression was significantly
      decreased in 9 of 10 lung cancer cell lines. This was associated with
      hypermethylation of the ANKRD18A promoter region. Moreover, weak expression of
      ANKRD18A in methylated lung cancer cell lines increased markedly after treatment
      with the DNA methylation inhibitor 5-aza-2'-deoxycytidine. These results suggest
      that ANKRD18A hypermethylation and consequent mRNA alterations might be a vital
      molecular mechanism in lung cancer.

PMID- 23131553
TI  - Neuronal overexpression of IP3 receptor 2 is detrimental in mutant SOD1 mice.
AB  - Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease
      causing progressive paralysis of the patient followed by death on average 3-5
      years after diagnosis. Disease pathology is multi-factorial including the process
      of excitotoxicity that induces cell death by cytosolic Ca(2+) overload. In this
      study, we increased the neuronal expression of an endoplasmic reticulum (ER)
      Ca(2+) release channel, inositol 1,4,5-trisphosphate receptor 2 (IP(3)R2), to
      assess whether increased cytosolic Ca(2+) originating from the ER is detrimental
      for neurons. Overexpression of IP(3)R2 in N2a cells using a Thy1.2-IP(3)R2
      construct increases cytosolic Ca(2+) concentrations evoked by bradykinin. In
      addition, mice generated from this construct have increased expression of IP(3)R2
      in the spinal cord and brain. This overexpression of IP(3)R2 does not affect
      symptom onset, but decreases disease duration and shortens the lifespan of the
      ALS mice significantly. These data suggest that ER Ca(2+) released by IP(3)
      receptors may be detrimental in ALS and that motor neurons are vulnerable to
      impaired Ca(2+) metabolism.

PMID- 23131554
TI  - ANT-VDAC1 interaction is direct and depends on ANT isoform conformation in vitro.
AB  - The voltage-dependent anion channel (VDAC) and the adenine nucleotide translocase
      (ANT) have central roles in mitochondrial functions such as nucleotides transport
      and cell death. The interaction between VDAC, an outer mitochondrial membrane
      protein and ANT, an inner membrane protein, was studied in isolated mitochondria
      and in vitro. Both proteins were isolated from various mitochondrial sources and
      reconstituted in vitro using a biomimetic system composed of recombinant human
      VDAC isoform 1 (rhVDAC1) immobilized on a surface plasmon resonance (SPR) sensor
      chip surface. Two enriched-preparations of (H)ANT (ANT from heart, mainly ANT1)
      and (L)ANT (ANT from liver, mainly ANT2) isoforms interacted differently with
      rhVDAC1. Moreover, the pharmacological ANT inhibitors atractyloside and
      bongkrekic acid modulated this interaction. Thus, ANT-VDAC interaction depends
      both on ANT isoform identity and on the conformation of ANT.

PMID- 23131555
TI  - Solid-state NMR analysis of the beta-strand orientation of the protofibrils of
      amyloid beta-protein.
AB  - Alzheimer's disease (AD) is caused by abnormal deposition (fibrillation) of a 42
      residue amyloid beta-protein (Abeta42) in the brain. During the process of
      fibrillation, the Abeta42 takes the form of protofibrils with strong
      neurotoxicity, and is thus believed to play a crucial role in the pathogenesis of
      AD. To elucidate the supramolecular structure of the Abeta42 protofibrils, the
      intermolecular proximity of the Ala-21 residues in the Abeta42 protofibrils was
      analyzed by (13)C-(13)C rotational resonance experiments in the solid state.
      Unlike the Abeta42 fibrils, an intermolecular (13)C-(13)C correlation was not
      found in the Abeta42 protofibrils. This result suggests that the beta-strands of
      the Abeta42 protofibrils are not in an in-register parallel orientation. Abeta42
      monomers would assemble to form protofibrils with the beta-strand conformation,
      then transform into fibrils by forming intermolecular parallel beta-sheets.

PMID- 23131556
TI  - Characterisation of human RING finger protein TRIM69, a novel testis E3 ubiquitin
      ligase and its subcellular localisation.
AB  - The E3 ubiquitin ligase activity and subcellular localisation of human TRIM69
      (hTRIM69) gene were studied. It was found that hTRIM69 mediated ubiquitination in
      an E2 conjugating enzyme selective fashion in vitro and an intact RING finger
      domain was indispensible for the process. Further evidences showed that hTRIM69
      could mediate ubiquitination in vivo, which could be enhanced by a proteasome
      inhibitor. hTRIM69 was found to localise in both the cytoplasm and the nucleus in
      a speckled aggregating pattern, which also required an intact RING finger domain.
      Collectively, hTRIM69 is a novel E3 ubiquitin ligase identified from human testis
      and may function to ubiquitinate its particular substrates during
      spermatogenesis.

PMID- 23131557
TI  - ssDNA-dsRNAs are cleaved at the next to its chimera-junction point by an unknown
      RNase activity.
AB  - We found that there is an unknown aspect in serum RNases that cleaves ssDNA-dsRNA
      and ssRNA-dsRNA. In the first step, RNase cleaves the phosphodiester linkage
      between the first and second RNA, where the first one is connected to the single
      stranded RNA or DNA. In the second step, the ssRNA overhang attached siRNA is
      cleaved. When the 2' hydroxyl of the first RNA was replaced with methoxy, the
      cleavage did not occur. This RNase activity can be considered related to defense
      system against exogenous genetic materials.

PMID- 23131558
TI  - DDR2 plays a role in fibroblast migration independent of adhesion ligand and
      collagen activated DDR2 tyrosine kinase.
AB  - Discoidin domain receptor-2 (DDR2) is a cell surface tyrosine kinase receptor
      that can be activated by soluble collagen and has been implicated in diverse
      physiological functions including organism growth and wound repair. In the
      current studies, we used fibronectin and collagen-coated 2D surfaces and collagen
      matrices in combination with siRNA technology to investigate the role of DDR2 in
      a range of fibroblast motile activities. Silencing DDR2 with siRNA inhibited cell
      spreading and migration, and similar inhibition occurred regardless whether cells
      were interacting with fibronectin or collagen surfaces. Under the assay
      conditions used, DDR2 tyrosine kinase activation was not observed unless soluble
      collagen was added to the incubation medium. Finally silencing DDR2 also
      inhibited human fibroblast migration in 3D collagen matrices but had no effect on
      3D collagen matrix remodeling and contraction. Taken together, our findings
      suggest that DDR2 is required for normal fibroblast spreading and migration
      independent of adhesion ligand and collagen activation of DDR2 tyrosine kinase.

PMID- 23131559
TI  - A single E105K mutation far from the active site of influenza B virus
      neuraminidase contributes to reduced susceptibility to multiple neuraminidase
      inhibitor drugs.
AB  - Drugs inhibiting the enzymatic activity of influenza virus neuraminidase (NA) are
      the cornerstone of therapy for influenza virus infection. The emergence of drug
      resistant variants may limit the benefits of antiviral therapy. Here we report
      the recovery of an influenza B virus with reduced susceptibilities to NA
      inhibitors from a human patient with no history of antiviral drug treatment. The
      virus, designated B/Kochi/61/2011, was isolated by inoculating Madin-Darby canine
      kidney (MDCK) cells with respiratory specimens from the patient. NA inhibition
      assays demonstrated that the B/Kochi/61/2011 isolate showed a remarkable
      reduction in susceptibility to peramivir. The isolate also exhibited low to
      moderately reduced sensitivity to oseltamivir, laninamivir, and zanamivir. A
      sequence analysis of viruses propagated in MDCK cells revealed that the isolate
      contained a mutation (E105K) not previously associated with reduced
      susceptibility to NA inhibitors. However, pyrosequencing analysis showed that the
      NA E105K mutation was below a detectable level in the original clinical
      specimens, suggesting that the mutant virus may be preferably selected during
      propagation in MDCK cells. Analysis of the three-dimensional model of E105 and
      K105 NAs with peramivir suggested that the E105K mutation at the monomer-monomer
      interface of the NA tetramer may destabilize the tetrameric form of NA, leading
      to decreased susceptibility to NA inhibitors. These results have implications for
      understanding the mechanism of resistance against NA-inhibitor drugs.

PMID- 23131560
TI  - Tumor necrosis factor superfamily member LIGHT induces epithelial-mesenchymal
      transition in A549 human alveolar epithelial cells.
AB  - Fibrosis is an abnormal response to organ injury, characterized by accumulation
      of activated fibroblasts at the sites of injury. Fibroblasts arise from several
      sources, including resident fibroblasts and circulating fibrocytes that
      infiltrate organ tissue. Recently, epithelial-mesenchymal transition (EMT) has
      been recognized as a source of mesenchymal cells. EMT is induced by various
      growth factors, such as transforming growth factor (TGF)-beta1, and enhanced by
      inflammatory cytokines. Recently the tumor necrosis factor superfamily member
      LIGHT has been implicated in the pathogenesis of inflammatory disease and airway
      remodeling in severe asthma. We hypothesized that LIGHT might contribute to the
      pathogenesis of airway fibrosis via enhancement of EMT. Therefore, we
      investigated LIGHT's ability to induce EMT. A549 cells were stimulated with
      LIGHT, TGF-beta1 or both for 48h. To estimate EMT, we evaluated the expression of
      epithelial and mesenchymal markers using immunocytochemistry, Western blotting
      and quantitative RT-PCR. Signaling pathways for EMT were characterized by Western
      analysis to detect phosphorylation of Erk1/2 and smad2. LIGHT enhanced TGF-beta1
      induced EMT both morphologically, by suppressing E-cadherin and enhancing
      vimentin, and functionally, by enhancing cell contractility. Additionally, LIGHT
      induced EMT without TGF-beta1. Evaluation of the mechanism showed that LIGHT did
      not induce TGF-beta1 production or affect the smad-snai1 pathway. Inhibition of
      Erk1/2 phosphorylation reduced LIGHT-induced EMT, indicating the Erk1/2 pathway
      to be a key pathway in LIGHT-induced EMT. In summary, LIGHT enhanced TGF-beta1
      induced EMT but also induced EMT via the Erk1/2 pathway by itself, without TGF
      beta1 signaling. LIGHT may contribute to the pathogenesis of airway fibrosis
      through enhancement of EMT.

PMID- 23131561
TI  - ETV6-NTRK3 as a therapeutic target of small molecule inhibitor PKC412.
AB  - The ETV6-NTRK3 (EN) fusion gene which encodes a chimeric tyrosine kinase was
      first identified by cloning of the t(12;15)(p13;q25) translocation in congenital
      fibrosarcoma (CFS). Since then, EN has been also found in congenital mesoblastic
      nephroma (CMN), secretory breast carcinoma (SBC) and acute myelogenous leukemia
      (AML). Using IMS-M2 and M0-91 cell lines harboring the EN fusion gene, and Ba/F3
      cells stably transfected with EN, we demonstrated that PKC412, also known as
      midostaurin, is an inhibitor of EN. Inhibition of EN activity by PKC412
      suppressed the activity of it downstream molecules leading to inhibition of cell
      proliferation and induction of apoptosis. Our data for the first time suggested
      that PKC412 could serve as therapeutic drug for treatment of patients with this
      fusion.

PMID- 23131562
TI  - Omega-3 polyunsaturated fatty acid has an anti-oxidant effect via the Nrf-2/HO-1
      pathway in 3T3-L1 adipocytes.
AB  - Oxidative stress is produced in adipose tissue of obese subjects and has been
      associated with obesity-related disorders. Recent studies have shown that omega-3
      polyunsaturated fatty acid (omega3-PUFA) has beneficial effects in preventing
      atherosclerotic diseases and insulin resistance in adipose tissue. However, the
      role of omega3-PUFA on adipocytes has not been elucidated. In this study, 3T3-L1
      adipocytes were treated with omega3-PUFA and its metabolites, eicosapentaenoic
      acid (EPA), docosahexaenoic acid (DHA), or 4-hydroxy hexenal (4-HHE). omega3-PUFA
      and its metabolites dose-dependently increased mRNA and protein levels of the
      anti-oxidative enzyme, heme oxygenase-1 (HO-1); whereas no changes in the well
      known anti-oxidant molecules, superoxide dismutase, catalase, and glutathione
      peroxidase, were observed. Knockdown of nuclear factor erythroid 2-related factor
      2 (Nrf-2) significantly reduced EPA, DHA or 4-HHE-induced HO-1 mRNA and protein
      expression. Also, pretreatment with omega3-PUFA prevented H(2)O(2)-induced
      cytotoxicity in a HO-1 dependent manner. In conclusion, treatment with EPA and
      DHA induced HO-1 through the activation of Nrf-2 and prevented oxidative stress
      in 3T3-L1 adipocytes. This anti-oxidant defense may be of high therapeutic value
      for clinical conditions associated with systemic oxidative stress.

PMID- 23131563
TI  - Genome-wide screen for Escherichia coli genes involved in repressing cell-to-cell
      transfer of non-conjugative plasmids.
AB  - Acquiring new genetic traits by lateral gene transfer is a bacterial strategy for
      environment adaptation. We previously showed that Escherichia coli could
      laterally transmit non-conjugative plasmids in co-cultures containing strains
      with and without the plasmid. In this study, using the Keio collection, a
      comprehensive library of E. coli knock-out mutants for non-essential genes, we
      screened for genes responsible for repressing cell-to-cell plasmid transfer in
      recipient cells. By stepwise screening, we identified 55 'transfer-up' mutants
      that exhibited approximately 2- to 30-fold increased activities. We confirmed
      plasmid acquisition by these 'up' mutants and revealed that there were no
      significant changes in antibiotic resistance in the original Keio strains. The
      presumed functions of these gene products covered a wide range of activities,
      including metabolism and synthesis, transport, transcription or translation and
      others. Two competence-gene homologues (ybaV and yhiR) were identified from among
      these genes. The presumed localizations of these 55 gene products were estimated
      to be 34 cytoplasmic proteins, 20 in or around the cell surface and 1 unknown
      location. Our results suggest that these 55 genes may be involved in repressing
      plasmid uptake during cell-to-cell plasmid transfer.

PMID- 23131564
TI  - Nuclear PIM1 confers resistance to rapamycin-impaired endothelial proliferation.
AB  - The PIM serine/threonine kinases and the mTOR/AKT pathway integrate growth factor
      signaling and promote cell proliferation and survival. They both share
      phosphorylation targets and have overlapping functions, which can partially
      substitute for each other. In cancer cells PIM kinases have been reported to
      produce resistance to mTOR inhibition by rapamycin. Tumor growth depends highly
      on blood vessel infiltration into the malignant tissue and therefore on
      endothelial cell proliferation. We therefore investigated how the PIM1 kinase
      modulates growth inhibitory effects of rapamycin in mouse aortic endothelial
      cells (MAEC). We found that proliferation of MAEC lacking Pim1 was significantly
      more sensitive to rapamycin inhibition, compared to wildtype cells. Inhibition of
      mTOR and AKT in normal MAEC resulted in significantly elevated PIM1 protein
      levels in the cytosol and in the nucleus. We observed that truncation of the C
      terminal part of Pim1 beyond Ser 276 resulted in almost exclusive nuclear
      localization of the protein. Re-expression of this Pim1 deletion mutant
      significantly increased the proliferation of Pim1(-/-) cells when compared to
      expression of the wildtype Pim1 cDNA. Finally, overexpression of the nuclear
      localization mutant and the wildtype Pim1 resulted in complete resistance to
      growth inhibition by rapamycin. Thus, mTOR inhibition-induced nuclear
      accumulation of PIM1 or expression of a nuclear C-terminal PIM1 truncation mutant
      is sufficient to increase endothelial cell proliferation, suggesting that nuclear
      localization of PIM1 is important for resistance of MAEC to rapamycin-mediated
      inhibition of proliferation.

PMID- 23131565
TI  - Transcriptional regulation of specific protein 1 (SP1) by hypoxia-inducible
      factor 1 alpha (HIF-1alpha) leads to PRNP expression and neuroprotection from
      toxic prion peptide.
AB  - Our previous study demonstrated that hypoxia-inducible factor-1 (HIF-1)-mediated
      neuroprotective effects are related to cellular prion protein (PrPc) gene (PRNP)
      regulation under hypoxic conditions. However, the mechanism of HIF-1alpha
      mediated PRNP gene regulation in prion-mediated neurodegenerative disorders is
      not clear. Transcription factor specific protein 1 (SP1) is necessary for PRNP
      transcription initiation, and SP1 gene expression is regulated through HIF-1alpha
      activation under hypoxic conditions. Thus, we hypothesized that HIF-1alpha
      mediated neuroprotection is related to the SP1 transcription pathway as a result
      of PRNP gene regulation. Inhibition of SP1 expression blocked the HIF-1alpha
      mediated protective effect against prion-mediated neurotoxicity. Also, knockdown
      of HIF-1alpha induced downregulation of SP1 expression and sensitivity to prion
      mediated neurotoxicity, whereas upregulation of SP1 transcriptional activity lead
      to protection against prion-mediated neuron cell death and PRNP gene expression
      even in HIF-1alpha depleted cells. This report is the first study demonstrating
      that HIF-1alpha-mediated SP1 expression regulates PrPc transcription, and
      upregulation of SP1 induced by HIF-1alpha plays a key role in protection from
      prion-mediated neurotoxicity. These studies suggest that transcription factor SP1
      may be involved in the pathogenesis of prion diseases and also may be a potential
      therapeutic option for neurodegeneration caused by the pathological prion
      protein, PrPsc.

PMID- 23131566
TI  - Calcium leak through ryanodine receptor is involved in neuronal death induced by
      mutant huntingtin.
AB  - Huntington's disease (HD) is a neurodegenerative disorder caused by an abnormal
      expansion of polyglutamine (polyQ) tract in huntingtin (htt) protein. Although
      altered calcium (Ca(2+)) homeostasis is suggested in HD, its molecular mechanisms
      have remained poorly understood despite their important role in the pathogenesis.
      In this study, we examined involvement of ryanodine receptor (RyR), an
      endoplasmic reticulum-resident Ca(2+) channel, in mutant htt-induced neuronal
      death. Inhibitors of RyR attenuated cell death induced by mutant htt, while co
      expression of RyR enhanced htt toxicity. Intracellular Ca(2+) imaging revealed
      that mutant htt caused excessive basal Ca(2+) release (Ca(2+) leak) through RyR
      leading to depletion of internal Ca(2+) store. Ca(2+) leak was also observed in
      striatal and cortical neurons from R6/2 HD model mice. Moreover, expression of
      FK506-binding protein 12 (FKBP12), a RyR stabilizer, suppressed both Ca(2+) leak
      and cell death. These results provide novel evidence suggesting altered RyR
      function is involved in neuronal cell death, and its stabilization might be
      beneficial for treatment of HD.

PMID- 23131568
TI  - A novel m.12908T>a mutation in the mitochondrial ND5 gene in patient with
      infantile-onset Pompe disease.
AB  - Pompe disease is a progressive metabolic myopathy caused by deficiency in
      lysosomal acid alpha-glucosidase and results in cellular lysosomal and
      cytoplasmic glycogen accumulation. A wide spectrum of clinical phenotypes exists
      from hypotonia and severe cardiac hypertrophy in the first few months of life to
      a milder form with the onset of symptoms in adulthood. The disease is typically
      due to severe mutations in GAA gene. In the present study, we described a newborn
      boy with clinical features of Pompe disease particularly with hypertrophic
      cardiomyopathy, hypotonia and hepatomegaly. This case was at first misdiagnosed
      as mitochondrial disorder. Accordingly, we performed a mitochondrial mutational
      analysis that revealed a novel mutation m.12908T>A in the ND5 gene. Secondary
      structure analysis of the ND5 protein further supported the deleterious role of
      the m.12908T>A mutation, as it was found to involve an extended imbalance in its
      hydrophobicity and affect its function.

PMID- 23131567
TI  - Developmental retardation, microcephaly, and peptiduria in mice without
      aminopeptidase P1.
AB  - Cytosolic aminopeptidase P1 (APP1) is one of the three known mammalian
      aminopeptidase Ps (APPs) that cleave the N-terminal amino acid residue of
      peptides in which the penultimate amino acid is proline. In mammals, many
      biologically active peptides have a highly conserved N-terminal penultimate
      proline. However, little is known about the physiological role of APP1. In
      addition, there is no direct evidence to associate a deficiency in APP1 with
      metabolic diseases. Although two human subjects with reduced APP activity
      exhibited peptiduria, it is unclear which of the three APP isoforms is
      responsible for this disorder. In this study, we generated APP1-deficient mice by
      knocking out Xpnpep1. Mouse APP1 deficiency causes severe growth retardation,
      microcephaly, and modest lethality. In addition, imino-oligopeptide excretion was
      observed in urine samples from APP1-deficient mice. These results suggest an
      essential role for APP1-mediated peptide metabolism in body and brain
      development, and indicate a strong causal link between APP1 deficiency and
      peptiduria.

PMID- 23131569
TI  - Activation of the cyclic AMP pathway promotes serotonin-induced Ca2+ oscillations
      in salivary glands of the blowfly Calliphora vicina.
AB  - Ca(2+) and cAMP signalling pathways interact in a complex manner at multiple
      sites. This crosstalk fine-tunes the spatiotemporal patterns of Ca(2+) and cAMP
      signals. In salivary glands of the blowfly Calliphora vicina fluid secretion is
      stimulated by serotonin (5-hydroxytryptamine, 5-HT) via activation of two
      different 5-HT receptors coupled to the InsP(3)/Ca(2+) (Cv5-HT(2alpha)) or the
      cAMP pathway (Cv5-HT(7)), respectively. We have shown recently in permeabilized
      gland cells that cAMP sensitizes InsP(3)-induced Ca(2+) release to InsP(3). Here
      we study the effects of the cAMP signalling pathway on 5-HT-induced oscillations
      in transepithelial potential (TEP) and in intracellular [Ca(2+)]. We show: (1)
      Blocking the activation of the cAMP pathway by cinanserin suppresses the
      generation of TEP and Ca(2+) oscillations, (2) application of 8-CPT-cAMP in the
      presence of cinanserin restores 5-HT-induced TEP and Ca(2+) oscillations, (3) 8
      CPT-cAMP sensitizes the InsP(3)/Ca(2+) signalling pathway to 5-HT and the Cv5
      HT(2alpha) receptor agonist 5-MeOT, (4) 8-CPT-cAMP induces Ca(2+) oscillations in
      cells loaded with subthreshold concentrations of InsP(3), (5) inhibition of
      protein kinase A by H-89 abolishes 5-HT-induced TEP and Ca(2+) spiking and mimics
      the effect of cinanserin. These results suggest that activation of the cyclic AMP
      pathway promotes the generation of 5-HT-induced Ca(2+) oscillations in blowfly
      salivary glands.

PMID- 23131570
TI  - The effect of sea buckthorn supplement on oral health, inflammation, and DNA
      damage in hemodialysis patients: a double-blinded, randomized crossover study.
AB  - OBJECTIVE: Chronic kidney disease is associated with inflammation, oxidative
      stress, malnutrition, poor oral health, and mouth dryness. The objective of this
      study was to evaluate effects of sea buckthorn oil (SBO) extract, which is rich
      in vitamins, phytochemicals, and polyunsaturated fatty acids, on oxidative
      stress, saliva production, and inflammation in hemodialysis patients. DESIGN
      SETTING AND SUBJECTS: This was a randomized, double-blinded, and placebo
      controlled crossover study (2 * 8 weeks, 4-week washout). The study subjects were
      hemodialysis patients (n = 45) recruited from the Department of Renal Medicine at
      Karolinska University Hospital in Stockholm. INTERVENTION AND MAIN OUTCOME
      MEASURES: The patients received 4 capsules per day, each containing 500 mg of SBO
      or placebo, for 8 weeks. They were then crossed over to the other treatment after
      a 4-week washout period. Salivary gland biopsies, saliva, and blood samples were
      collected before and after each treatment period. Main outcomes were DNA breaks
      and oxidative DNA lesions in minor accessory salivary glands, salivary flow
      rates, and inflammation markers in blood (high-sensitivity C-reactive protein,
      antitrypsin, orosomucoid in plasma, leukocytes in blood). Blood markers including
      creatinine, urea in plasma, and hemoglobin in blood were investigated. RESULTS:
      The results showed no significant changes in DNA breaks, oxidative DNA lesions,
      salivary flow rates, or inflammation after SBO supplementation. However, plasma
      levels of phosphate and sodium increased and plasma levels of iron decreased.
      CONCLUSION: In conclusion, SBO supplementation as performed in this study did not
      protect against oxidative stress, nor improve oral health or inflammation status
      in hemodialysis patients.

PMID- 23131571
TI  - Urinary phosphate excretion and fibroblast growth factor 23 in chronic kidney
      disease.

PMID- 23131572
TI  - Long-term fish intake preserves kidney function in elderly individuals: the
      Ikaria study.
AB  - OBJECTIVES: The aim of this work was to evaluate the correlation between the
      amount of weekly fish intake and kidney function as measured by creatinine
      clearance (CCr) rate among elderly inhabitants of Ikaria Island, a place that has
      been related to an increased rate of longevity. METHODS: From June to October of
      2009, 673 males and females, aged 65-100 years and long-term residents of Ikaria
      Island were enrolled. Of those, 328 (75 +/- 7 years) were males and 339 (75 +/- 6
      years) were females. Nutritional habits, including fish intake, were evaluated
      using a validated, semi-frequent food questionnaire and the MedDietScore. Urea
      and creatinine were measured, and CCr rate was estimated by the Cockcroft-Gault
      formula. RESULTS: Eighty-four percent of participants reported fish consumption
      of more than 150 g/week; 35% had moderate to severe CCr (<60 mL). Crude analysis
      revealed that CCr rate was positively associated with fish intake (b +/- SE per
      100 g/day: 24 +/- 9, P = .007); multiple linear regression analysis confirmed the
      previous finding (b +/- SE per 100 g/day: 11 +/- 2, P = .001) after adjusting for
      overall dietary habits through the MedDietScore and other potential confounders.
      Fish intake was positively associated with CCr. Furthermore, multi-adjusted
      logistic regression analysis showed that fish consumption of 100 g/day increased
      the likelihood by 121% of having a CCr greater than 60 mL (95% confidence
      interval 10%-343%). CONCLUSIONS: Long-term fish consumption was independently
      associated with improved kidney function among elderly individuals, a finding
      that extends the current knowledge regarding the benefits of fish intake on human
      health.

PMID- 23131573
TI  - Effects of urate-lowering therapy in hyperuricemia on slowing the progression of
      renal function: a meta-analysis.
AB  - Uric acid (UA) is generally regarded as an independent risk factor for poor
      prognosis of patients with kidney disease. However, urate-lowering therapy (ULT)
      in asymptomatic hyperuricemia is conservative. Whether the beneficial effect on
      renal function can be achieved by lowering UA remains uncertain. A compound
      search for randomized controlled trials was conducted in databases consisting of
      MEDLINE, EMBASE, the Cochrane Library, the Chinese Biomedical Literature
      Database, and Chinese Science and Technology periodical databases. Two
      investigators independently screened these studies, assessed the included trials,
      and extracted data. Eleven articles with a total number of 753 participants met
      the criteria and were included in our meta-analysis. The results showed that ULT
      was associated with a decrease in serum creatinine and an increase in eGFR. Our
      study further confirms that ULT may have beneficial effects on slowing the
      progression of renal function. 

PMID- 23131574
TI  - Nonprotein calorie supplement improves adherence to low-protein diet and exerts
      beneficial responses on renal function in chronic kidney disease.
AB  - OBJECTIVE: Malnutrition is common in patients with chronic kidney disease (CKD)
      who are on low-protein diets and is a powerful predictor of morbidity and
      mortality in CKD. Studies have shown that patients on low-protein diets often
      have difficulty meeting nutritional energy requirements. Our study evaluated the
      effects of a nonprotein calorie (NPC) supplement on renal function and
      nutritional status in patients on a low-protein diet. DESIGN: This was a
      prospective, randomized, open-label, controlled clinical trial. SUBJECTS: A total
      of 109 patients with CKD (men, 67%; mean age, 54.5 +/- 13 years) with stage 3 to
      4 disease were randomly assigned to the intervention group (n = 55) or the
      control group (n = 54). INTERVENTION: All participants received individualized
      dietary counseling aimed at achieving a daily protein intake of 0.6 to 0.8 g and
      a daily energy intake of 30 to 35 kcal/kg. The intervention group consumed a 200
      kcal NPC supplement daily. The control group received dietary counseling only.
      MAIN OUTCOME MEASURE: The estimated glomerular filtration rate (eGFR) was
      calculated using the 4-variable Modification of Diet in Renal Disease (MDRD)
      Study equation. Urine protein excretion, dietary protein and energy intake, and
      serum levels of creatinine, urea nitrogen, cholesterol, triglycerides, and
      albumin were assessed at baseline, at 12 weeks, and at 24 weeks. RESULTS: Dietary
      protein intake and urine protein excretion levels decreased significantly in the
      intervention group and were significantly lower than those of the control group.
      In addition, serum levels of creatinine and urea nitrogen decreased
      significantly, and eGFR increased significantly in the intervention group
      compared with baseline assessments. No significant differences were observed in
      the control group. CONCLUSIONS: The NPC supplement improved patient adherence to
      the low-protein diet and reduced urine protein excretion in patients with CKD.

PMID- 23131575
TI  - [Acute tolerance and opioid-induced hyperalgesia in a multi-operated patient].

PMID- 23131576
TI  - Potential ecological distribution of Cytauxzoon felis in domestic cats in
      Oklahoma, Missouri, and Arkansas.
AB  - The ecological distribution of Cytauxzoon felis, an often-fatal tick-borne
      apicomplexan that infects domestic cats, has not been evaluated or identified
      despite its continued emergence. Infection of C. felis is characterized by
      lethargy, icterus, fever, anorexia, anemia, and death. The natural vertebrate
      reservoir of C. felis is the bobcat (Lynx rufus). To determine the possible
      distribution of C. felis in three states where infection is common (Oklahoma,
      Missouri, and Arkansas), two separate approaches to ecological niche modeling
      were implemented. First, a model relating several different climatic layers to
      geographic locations where cases of C. felis infection were confirmed in domestic
      cats was developed to predict the possible distribution of the parasite. The
      second model incorporated occurrences of bobcats with environmental layers and
      land cover suitable for tick vectors to identify areas of overlap where C. felis
      transmission was likely. Results of both models indicated a high probability of
      C. felis from central Oklahoma to south-central Missouri. However, other
      predicted areas of C. felis occurrence varied between the two modeling
      approaches. Modeling the vertebrate reservoir and the tick vector predicted a
      broader possible distribution compared to modeling cases of C. felis infection in
      domestic cats. Our results suggest that C. felis is likely to extend beyond areas
      predicted by case modeling due to the presence of both the vector and reservoir.

PMID- 23131577
TI  - On the aggregated nature of chronic Sarcoptes scabiei infection in adult pigs.
AB  - The prevalence and body distribution of Sarcoptes scabiei and associated
      dermatitis was investigated in sows and boars from four herds with long standing
      mange. Macroscopic hyperkeratotic dermatitis (crusted mange) was present in 1-6%
      of herd sows. Mite estimated prevalence (95% CI) in ear scrapings was 11% (6-17%)
      including 100% (13/13) and 2% (3/134) in sows with and without crusted mange,
      respectively, and the later had very few mites compared to the former. S. scabiei
      body distribution and dermatitis were further investigated in 59-64 skin
      scrapings/sow taken post-mortem from four culled sows including two (sows 1 and
      2) with and two (sows 3 and 4) without crusted mange. The proportion of skin
      samples with eggs, instars or adults was 59% in sow 1, 84% in sow 2, 0% in sow 3
      and 3% in sow 4. S. scabiei distribution in sows 1 and 2 ranged from being
      present in all skin ear and head samples to absent in those from the inner side
      of the limbs and mammary glands. Crusted lesions were observed in the skin of the
      ears, neck and lower limbs and contained the largest mite populations.
      Histopathological analysis of skin samples identified mites, inflammatory
      cellular infiltrate (mainly lymphocytes, neutrophils and eosinophils) and
      hyperkeratosis, acanthosis and spongiosis in 78%, 54%, 20% and 25% of samples
      from sows 1, 2, 3 and 4, respectively, being lesion severity positively
      associated to mite presence. The study provides further evidence that in herds
      with long-standing exposure to S. scabiei, infection becomes highly overdispersed
      with large mite populations present only in a few pigs and in specific body
      areas. Although the reasons for mite aggregation have not been identified, it is
      important controlwise because treating or eliminating a few and easy to identify
      heavily infected adult pigs, should markedly decrease the herd's parasite load
      and reduce the use of acaridal drugs.

PMID- 23131578
TI  - Deaf children attending different school environments: sign language abilities
      and theory of mind.
AB  - The present study examined whether full access to sign language as a medium for
      instruction could influence performance in Theory of Mind (ToM) tasks. Three
      groups of Italian participants (age range: 6-14 years) participated in the study:
      Two groups of deaf signing children and one group of hearing-speaking children.
      The two groups of deaf children differed only in their school environment: One
      group attended a school with a teaching assistant (TA; Sign Language is offered
      only by the TA to a single deaf child), and the other group attended a bilingual
      program (Italian Sign Language and Italian). Linguistic abilities and
      understanding of false belief were assessed using similar materials and
      procedures in spoken Italian with hearing children and in Italian Sign Language
      with deaf children. Deaf children attending the bilingual school performed
      significantly better than deaf children attending school with the TA in tasks
      assessing lexical comprehension and ToM, whereas the performance of hearing
      children was in between that of the two deaf groups. As for lexical production,
      deaf children attending the bilingual school performed significantly better than
      the two other groups. No significant differences were found between early and
      late signers or between children with deaf and hearing parents.

PMID- 23131580
TI  - Prevalence of psychiatric disorders in older patients attending an Arab tertiary
      facility.

PMID- 23131581
TI  - Epidural abscess and cauda equina syndrome after percutaneous intradiscal therapy
      in degenerative lumbar disc disease.
AB  - BACKGROUND CONTEXT: Percutaneous intradiscal therapies are gaining popularity as
      a regenerative treatment option for spinal disc degeneration. The risks,
      benefits, and possible complications associated with such procedures have been
      poorly defined. As these procedures are performed with increasing frequency, the
      likelihood that clinicians will be faced with significant complications also
      increases. PURPOSE: The purpose of this study is to describe a significant
      complication of a percutaneous intradiscal bone marrow and adipose tissue
      transplantation for symptomatic lumbar disc degeneration. STUDY DESIGN: The study
      design is a case report. METHODS: Two weeks after an injection of adipose cells,
      bone marrow aspirate and plasma into his L3-L4 and L5-S1 lumbar discs, a 64-year
      old patient presented to the emergency room with cauda equina syndrome, fever,
      and back pain. Magnetic resonance imaging diagnosed L3-L4 disc extrusion,
      discitis with osteomyelitis, and epidural abscess, resulting in emergency
      decompressive surgery. An epidural abscess was drained, extruded disc material
      was removed, and cultures obtained. Five days later, once afebrile on
      antibiotics, he underwent a definitive interbody arthrodesis and stabilization.
      RESULTS: Cauda equina syndrome resolved, osteomyelitis (methicillin-resistant
      Staphylococcus epidermidis) was treated, and instrumented arthrodesis stabilized
      the involved segment. CONCLUSIONS: Complications associated with the intradiscal
      injection of agents, such as stem cells, fibrin glue, adipose tissue, or bone
      marrow, have been poorly defined. Given the nature of the degenerating disc,
      serious adverse events, including discitis, osteomyelitis, and extrusion of disc
      contents, may occur.

PMID- 23131582
TI  - Histopathological studies of microtubule disassembling agent-induced myocardial
      lesions in rats.
AB  - Microtubule disassembling agents (MDAs) such as colchicine (COL) and vincristine
      sulfate (VCR) are known to be cardiotoxic. However, few attempts have been made
      to histopathologically examine cardiac lesions induced by MDAs. In this study, we
      endeavored to induce myocardial injury in rats by administering MDAs and to
      clarify the morphological features of these myocardial lesions. Male rats were
      intravenously administered COL (1.00 or 1.25mg/kg for 2 days at single daily
      doses) or VCR (0.50 or 0.75 mg/kg for 2 days at single daily doses). The day
      after administration, hearts were excised and examined histopathologically,
      immunohistochemically and electron microscopically. Degeneration and necrosis of
      myocardial cells with vacuolation were observed in rats administered COL at
      1.25mg/kg or VCR at 0.75 mg/kg. Electron microscopic examination revealed
      vacuoles in swollen mitochondria. Moreover, there were cells showing pyknosis and
      karyorrhexis in the interstitium. TUNEL and immunohistochemical staining for
      endothelial cells and electron microscopic examination identified the apoptotic
      cells in the interstitium to be vascular endothelial cells. These vascular
      endothelial lesions were induced by lower doses of MDAs than were myocardial
      lesions. Furthermore, common sites of cardiac lesions induced by MDAs had almost
      the same distribution as areas positive for pimonidazole, a marker of hypoxia.
      These findings indicate that MDAs occasionally damage mitochondria in myocardial
      cells, and suggest that these changes involve microcirculatory dysfunction
      induced by endothelial cell injury.

PMID- 23131583
TI  - Non-homologous end joining mediated DNA repair is impaired in the NUP98-HOXD13
      mouse model for myelodysplastic syndrome.
AB  - Chromosomal translocations typically impair cell differentiation and often
      require secondary mutations for malignant transformation. However, the role of a
      primary translocation in the development of collaborating mutations is debatable.
      To delineate the role of leukemic translocation NUP98-HOXD13 (NHD13) in secondary
      mutagenesis, DNA break and repair mechanisms in stimulated mouse B lymphocytes
      expressing NHD13 were analyzed. Our results showed significantly reduced
      expression of non-homologous end joining (NHEJ)-mediated DNA repair genes, DNA
      Pkcs, DNA ligase4, and Xrcc4 leading to cell cycle arrest at G2/M phase. Our
      results showed that expression of NHD13 fusion gene resulted in impaired NHEJ
      mediated DNA break repair.

PMID- 23131584
TI  - Fluoxetine suppresses synaptically induced [Ca2+]i spikes and excitotoxicity in
      cultured rat hippocampal neurons.
AB  - Fluoxetine is a widely used antidepressant with an action that is primarily
      attributed to the inhibition of serotonin re-uptake into the synaptic terminals
      of the central nervous system. Fluoxetine also has blocking effects on various
      ion channels, including Ca(2+) channels. It remains unclear, however, how
      fluoxetine may affect synaptically induced [Ca(2+)](i) spikes. We investigated
      the effects of fluoxetine on [Ca(2+)](i) spikes, along with the subsequent
      neurotoxicity that is synaptically evoked by lowering extracellular Mg(2+) in
      cultured rat hippocampal neurons. Fluoxetine inhibited the synaptically induced
      [Ca(2+)](i) spikes in p-chloroamphetamine-treated and non-treated neurons, in a
      concentration-dependent manner. However, other selective serotonin reuptake
      inhibitors, such as paroxetine and citalopram, did not significantly affect the
      spikes. Pretreatment with fluoxetine for 5 min inhibited [Ca(2+)](i) increases
      induced by glutamate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid,
      and N-methyl-d-aspartate. Fluoxetine also inhibited alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid-induced currents. In addition, fluoxetine
      decreased the [Ca(2+)](i) responses induced by the metabotrophic glutamate
      receptor agonist (S)-3,5-dihydroxyphenylglycine or the ryanodine receptor agonist
      caffeine. Fluoxetine inhibited [Ca(2+)](i) responses induced by 20mM KCl.
      Fluoxetine decreased the release of FM1-43 induced by electric field stimulation.
      Furthermore, fluoxetine inhibited 0.1mM [Mg(2+)](o)-induced cell death.
      Collectively, our results suggest that fluoxetine suppresses the spikes and
      protects neurons against excitotoxicity, particularly in cultured rat hippocampal
      neurons, presumably due to both direct inhibition of presynaptic glutamate
      release and postsynaptic glutamate receptor-mediated [Ca(2+)](i) signaling. In
      addition to an indirect inhibitory effect via 5-HT levels, these data suggest a
      new, possibly direct inhibitory action of fluoxetine on synaptically induced
      [Ca(2+)](i) spikes and neuronal cell death.

PMID- 23131585
TI  - Hippocampal neuronal loss, decreased GFAP immunoreactivity and cognitive
      impairment following experimental intoxication of rats with aluminum citrate.
AB  - Aluminum (Al) is a neurotoxic agent with deleterious actions on cognitive
      processes. Nevertheless, few studies have investigated the neuropathological
      effects underlying the Al-induced cognitive impairment. We have explored the
      effects of acute Al citrate intoxication on both hippocampal morphology and
      mnemonic processes in rodents. Adult male Wistar rats were intoxicated with a
      daily dose of Al citrate (320 mg/kg) during 4 days by gavage. Animals were
      perfused at 8 (G2), 17 (G3) and 31 days (G4) after intoxication. Control animals
      were treated with sodium citrate (G1). Animals were submitted to behavioral tests
      of open field and elevated T-maze. Immunohistochemistry was performed to label
      neurons (anti-NeuN) and astrocytes (anti-GFAP) in both CA1 and CA3 hippocampal
      regions. There was an increase in the locomotor activity in open field test for
      G2 in comparison to control group and other groups (ANOVA-Bonferroni, P<0.05).
      The elevated T-maze avoidance latency (AL) was higher in all intoxicated groups
      compared to control (P<0.05) in avoidance 1. These values remained elevated in
      avoidance 2 (P<0.05), but abruptly decreased in G2 and G3, but not in G1 and G4
      animals in avoidance 3 (P<0.05). There were no significant differences for 1 and
      2 escape latencies. There were intense neuronal loss and a progressive decrease
      in GFAP immunoreactivity in the hippocampus of intoxicated animals. The results
      suggest that Al citrate treatment induces deficits on learning and memory
      concomitant with neuronal loss and astrocyte impairment in the hippocampus of
      intoxicated rats.

PMID- 23131586
TI  - [If Hippocrates was among us... About the no-attention to "illegal" immigrants].

PMID- 23131587
TI  - [Your doctor recommends you have a little more confidence].

PMID- 23131588
TI  - Understanding factors influencing Latina women's screening behavior: a
      qualitative approach.
AB  - The purpose of this qualitative study was to understand influential factors
      associated with decisions to obtain breast or cervical cancer screening by
      diverse Latinas after attending a community-based educational program. Forty-five
      interviews were conducted in Arkansas, New York City and Buffalo, New York.
      Thematic data analyses were conducted to understand influential factors following
      from the intervention. Four major themes emerged from the interviews: Social
      Capital, Screening Utilization, Health Care Provider (HCP) Communication and
      Social Networks. Social Capital included resources, access or screening knowledge
      women had prior to participation in the program and new resources and contacts
      gained through the program that influenced care seeking. Screening Utilization
      factors included past health experiences and participation in the program. HCP
      Communication included perceptions of quality of care and communication issues
      with HCPs that positively and negatively impacted screening. Social Networks
      included women's networks regarding emotional support, encouragement to discuss
      health issues, overall family network and how these may influence health-seeking
      behaviors. These findings suggest that participating in group-based health
      outreach programs empowered women by increasing their knowledge and awareness
      about the health care system and enabled them, with the tools provided, to become
      proactive in their health care-seeking behaviors.

PMID- 23131589
TI  - Expression and distribution of aggrecanases in human larynx: ADAMTS-5/aggrecanase
      2 is the main aggrecanase in laryngeal carcinoma.
AB  - Members of the ADAMTS family of proteases degrade proteoglycans and thereby have
      the potential to alter tissue architecture and regulate cellular functions.
      Aggrecanases are the main enzymes responsible for aggrecan degradation, due to
      their specific cleavage pattern. In this study, the expression status, the
      macromolecular organization and localization of ADAMTS-1, ADAMTS-4/aggrecanase-1
      and ADAMTS-5/aggrecanase-2 in human normal larynx and laryngeal squamous cell
      carcinoma (LSCC) were investigated. On mRNA level, the results showed that ADAMTS
      4 was the highest expressed enzyme in normal larynx, whereas ADAMTS-5 was the
      main aggrecanase in LSCC presenting a stage-related increase up to stage III (8
      fold higher expression compared to normal), and thereafter decreased in stage IV.
      Accordingly, immunohistochemical analysis showed that ADAMTS-5, but not ADAMTS-4,
      was highly expressed by carcinoma cells. Sequential extraction revealed an
      altered distribution and organization of multiple molecular forms (latent,
      activated and fragmented forms) of the enzymes within the cancerous and their
      corresponding macroscopically normal laryngeal tissues, compared to the normal
      ones. Importantly, these analyses indicated that critical macromolecular changes
      occurred from the earliest LSCC stages not only in malignant parts of the tissue
      but also in areas that were not in proximity to carcinoma cells and appeared
      otherwise normal. Overall, the results of the present study show that ADAMTS
      5/aggrecanase-2 is the main aggrecanase present in laryngeal carcinoma suggesting
      a critical role for the enzyme in aggrecan degradation and laryngeal tissue
      destruction during tumor progression.

PMID- 23131590
TI  - Is carotenoid ornamentation linked to the inner mitochondria membrane potential?
      A hypothesis for the maintenance of signal honesty.
AB  - Several mechanistic hypotheses have been proposed for how carotenoid pigmentation
      of integumentary structures can serve as an honest signal of individual quality.
      These hypotheses are founded on proposed links between carotenoids, immuno
      responsiveness, and oxidative stress, but an absence of biochemical information
      on the oxidative pathways of carotenoids has limited the sophistication of such
      hypotheses. Based on published evidence, we propose that the oxidation of
      carotenoids for the purpose of ornamentation in birds and reptiles is coupled to
      the inner mitochondria membrane. We predict that several carotenoid oxidation
      reactions yielding ornamental pigments occur on the inner mitochondrial membrane.
      Three of these reactions are proposed to occur within the ubiquinone biosynthesis
      cluster known as the Coq cluster consisting of approximately a dozen Coq members,
      tightly integrated and intimately associated with Complex I and III of the
      electron transport system. Ubiquinone and highly oxidized ornamental carotenoids
      share a stereochemically-conserved binding region suggesting that these two
      molecules may have shared similar pathways in the past. Carotenoids and
      ubiquinones may cooperate as redox participants in anti-radical reactions or
      independently in helping to maintain membrane or supra-complex stabilization
      during times of high-energy demand. Under this hypothesis, oxidation of
      carotenoids is coupled to the inner mitochondria membrane potential such that
      ornamental coloration reflects the efficiency of cellular respiration.

PMID- 23131591
TI  - An integrated approach to the ligand binding specificity of Neisseria
      meningitidis M1 alanine aminopeptidase by fluorogenic substrate profiling,
      inhibitory studies and molecular modeling.
AB  - Neisseria meningitides is a gram-negative diplococcus bacterium and is the main
      causative agent of meningitis and other meningococcal diseases. Alanine
      aminopeptidase from N. meningitides (NmAPN) belongs to the family of metallo
      exopeptidase enzymes, which catalyze the removal of amino acids from the N
      terminus of peptides and proteins, and are found among all the kingdoms of life.
      NmAPN is suggested to be mostly responsible for proteolysis and nutrition
      delivery, similar to the orthologs from other bacteria. To explore the
      possibility of NmAPN being a potential drug target for inhibition and development
      of novel therapeutic agents, the specificity of the S1 and S1' binding sites was
      explored using an integrated approach. Initially, an extensive library consisting
      of almost 100 fluorogenic substrates derived from both natural and unnatural
      amino acids, were used to obtain a detailed substrate fingerprint of the S1
      pocket of NmAPN. A broad substrate tolerance of NmAPN was revealed, with bulky
      basic and hydrophobic ligands being the most favored substrates. Additionally,
      the potency of a set of organophosphorus inhibitors of neutral aminopeptidases,
      amino acid and dipeptide analogs was determined. Inhibition constants in the
      nanomolar range, determined for phosphinic dipeptides, proves the positive
      increase in inhibition impact of the P1' ligand elongation. The results were
      further verified via molecular modeling and docking of canonical aminopeptidase
      phosphinic dipeptide inhibitors in the NmAPN active site. These studies present
      comprehensive characterization of interactions responsible for specific ligand
      binding. This knowledge provides invaluable insight into understanding of the
      enzyme and development of novel NmAPN inhibitors.

PMID- 23131592
TI  - Parameter identification for a local field potential driven model of the
      Parkinsonian subthalamic nucleus spike activity.
AB  - Several models, with various degrees of complexity have been proposed to model
      the neuronal activity from different parts of the human brain. We have shown
      before that various modeling approaches, including a Hammerstein-Wiener (H-W)
      model, can be used to predict the spike trains from a deep nucleus, the
      subthalamic nucleus, using the underlying local field potentials. In this
      article, we present, in depth, the various choices one has to make, and the
      limitations that they introduce, during the H-W model parameter identification
      process. From a segment of the recorded data, which contains information about
      the spike times of a single neuron, we identify and extract the model parameters.
      We then use those parameters to numerically simulate the spike timing, the rhythm
      and the inter-spike intervals for the rest of the recording. To assess how well
      the model fits to the measured data we combine measures of spike train synchrony,
      namely the Victor-Purpura distance and the Gaussian similarity measure, with time
      scale independent train distances. We show that a wise combination of metrics
      results in models that predict the spikes with temporal accuracy ranging, on
      average, from 53% to more than 80%, depending on the number of the neurons'
      spikes recorded. The model's prediction is adequate for estimating accurately the
      spike rhythm. Quantitative results establish the model's validity as a simple yet
      biologically plausible model of the spike activity recorded from a deep nucleus
      inside the human brain.

PMID- 23131593
TI  - Salivary cortisol and interpersonal functioning: an event-contingent recording
      study in the offspring of parents with bipolar disorder.
AB  - Despite a large body of research in non-human primates, the relationship between
      naturalistic patterns of social behaviour and basal cortisol levels has been
      understudied in humans. The present study examined the relationship between
      patterns of interpersonal functioning and cortisol levels in 23 offspring of
      parents with bipolar disorder (BD), at high risk for the development of an
      affective disorder, and 22 offspring of parents with no affective disorder
      (controls) in late adolescence and young adulthood. Using event-contingent
      recording, participants rated their dominance, submissiveness, quarrelsomeness,
      and agreeableness in naturally occurring social interactions over 14 consecutive
      days and provided salivary cortisol twice daily in the afternoon over the same
      period. In the full sample, multilevel modelling analyses revealed that dominance
      was a significant positive predictor of afternoon basal cortisol levels,
      t(35)=2.58, p<0.05. Moreover, risk group (having a parent with BD or parents with
      no affective disorder) significantly interacted with mean levels of
      quarrelsomeness to predict afternoon cortisol levels, t(29)=2.06, p<0.05.
      Offspring of parents with BD who reported more frequent quarrelsome behaviours
      exhibited lower levels of afternoon cortisol relative to high-risk offspring
      reporting few quarrelsome behaviours and control offspring. The results are
      consistent with evidence that dominance is associated with high cortisol levels
      in an unstable environment, and suggest that quarrelsomeness among high risk
      youth contributes to altered hypothalamic-pituitary-adrenal activity.

PMID- 23131595
TI  - Alkaline phosphatase as a treatment of sepsis-associated acute kidney injury.
AB  - Currently there are no pharmacological therapies licensed to treat sepsis
      associated acute kidney injury (AKI). Considering the high incidence and
      mortality of sepsis-associated AKI, there is an urgent medical need to develop
      effective pharmacological interventions. Two phase II clinical trials recently
      demonstrated beneficial effects of the enzyme alkaline phosphatase (AP). In
      critically ill patients with sepsis-associated AKI, treatment with AP reduced the
      urinary excretion of tubular injury biomarkers and plasma markers of
      inflammation, which was associated with improvement of renal function. The
      dephosphorylating enzyme, AP, is endogenously present in the renal proximal
      tubule apical membrane but becomes depleted during ischemia-induced AKI, thereby
      possibly contributing to further renal damage. The exact mechanism of action of
      AP in AKI is unknown, but might be related to detoxification of circulating
      lipopolysaccharide and other proinflammatory mediators that lose their
      proinflammatory effects after dephosphorylation. Alternatively, tissue damage
      associated with systemic inflammation might be attenuated by an AP-mediated
      effect on adenosine metabolism. Adenosine is a signaling molecule that has been
      shown to protect the body from inflammation-induced tissue injury, which is
      derived through dephosphorylation of ATP. In this Perspectives article, we
      discuss the clinical activity of AP and its putative molecular modes of action,
      and we speculate on its use to treat and possibly prevent sepsis-associated AKI.

PMID- 23131594
TI  - Local control in advanced cancer of the nasopharynx: is a boost dose by
      endocavitary brachytherapy of prognostic significance?
AB  - PURPOSE: To analyze whether local tumor control in advanced nasopharyngeal cancer
      (NPC) can be optimized by boosting the primary dose by endocavitary brachytherapy
      (EBT). METHODS AND MATERIALS: To study the role of EBT, three data sets on NPC,
      that is, the "Vienna", "Rotterdam," and "Amsterdam" series, with a total number
      of 411 advanced NPC patients, were available. The Rotterdam series consisted of
      72 patients (34 T1,2N+ and 38 T3,4N0,+) and were treated with neoadjuvant
      chemotherapy followed by external beam radiotherapy (dose 70/2Gy). After 70/2Gy,
      a boost was applied by EBT (in case of T1,2N+) or stereotactic radiation (in case
      of T3,4 tumors). The Amsterdam (Antoni van Leeuwenhoek Hospital/The Netherlands
      Cancer Institute) series consisted of 76 patients (40 T1,2N+ and 36 T3,4N0,+) and
      were irradiated to a dose of 70/2Gy with concomitant chemotherapy. No second
      boost by EBT was applied. RESULTS: In the case of T1,2N+ tumors, the local
      relapse rate (LRR) was significantly smaller if a boost was applied, that is, 0%
      (0/34, EBT boost) vs. 14% (14/102, no EBT boost) (p=0.023). For the T3,4 tumors,
      an LRR of 10% (4/38, EBT or stereotactic radiation boost) vs. 15% (17/111, no
      boost) was found (p=0.463). CONCLUSIONS: In the case of advanced NPC (T1,2N+ vs.
      T3,4N+,0), for early T-stages (T1,2N+), an EBT boost seems an excellent way to
      deliver highly conformal high doses of radiation to the nasopharynx, with high
      local control rates. For advanced T-stages (T3,4N+,0), the reduction in LRR (10%
      vs. 15%) was not significant (p=0.463).

PMID- 23131597
TI  - Prospective analysis of incidence, extent and chronicity of lower extremity
      venous thrombosis.
AB  - OBJECTIVE: This study was designed to determine all variables related to lower
      extremity deep venous thrombosis (DVT) to be used as reference in patients
      examined in a hospital setting. METHODS: Consecutive patients presented with
      signs and symptoms of venous thromboembolism over a one-year period, examined in
      our university hospital. Patients' demographics and clinical characteristics in a
      data base organized to answer all the pertinent questions. RESULTS: There were
      2594 patients. Thrombosis was found in 348 (13.4%) of which 249 were acute and 72
      had chronic luminal changes. Unilateral thrombosis was found in 268 and bilateral
      in 80. Acute DVT and/or chronic changes were more common on the left limb.
      Chronic thrombosis was more prevalent in the proximal veins. Acute thrombosis was
      more often found in the inpatients. Both acute DVT and chronic changes were found
      in 27 patients (7.8%) of whom 15 were bilateral. CONCLUSIONS: Various patterns of
      thrombosis are found in both inpatients and outpatients with the former having a
      higher incidence of acute events. Acute, chronic and recurrent thrombosis are
      very frequent and very important to report as they could change the management of
      the patients.

PMID- 23131596
TI  - In vitro pharmacological characterization of vilanterol, a novel long-acting
      beta2-adrenoceptor agonist with 24-hour duration of action.
AB  - Vilanterol trifenatate (vilanterol) is a novel, long-acting beta(2)-adrenoceptor
      (beta(2)-AR) agonist with 24 h activity. In this study, we describe the
      preclinical pharmacological profile of vilanterol using radioligand binding and
      cAMP studies in recombinant assays as well as human and guinea pig tissue systems
      to characterize beta(2)-AR binding and functional properties. Vilanterol
      displayed a subnanomolar affinity for the beta(2)-AR that was comparable with
      that of salmeterol but higher than olodaterol, formoterol, and indacaterol. In
      cAMP functional activity studies, vilanterol demonstrated similar selectivity as
      salmeterol for beta(2)- over beta(1)-AR and beta(3)-AR, but a significantly
      improved selectivity profile than formoterol and indacaterol. Vilanterol also
      showed a level of intrinsic efficacy that was comparable to indacaterol but
      significantly greater than that of salmeterol. In cellular cAMP production and
      tissue-based studies measuring persistence and reassertion, vilanterol had a
      persistence of action comparable with indacaterol and longer than formoterol. In
      addition, vilanterol demonstrated reassertion activity in both cell and tissue
      systems that was comparable with salmeterol and indacaterol but longer than
      formoterol. In human airways, vilanterol was shown to have a faster onset and
      longer duration of action than salmeterol, exhibiting a significant level of
      bronchodilation 22 h after treatment. From these investigations, the data for
      vilanterol are consistent, showing that it is a novel, potent, and selective
      beta(2)-AR receptor agonist with a long duration of action. This pharmacological
      profile combined with clinical data is consistent with once a day dosing of
      vilanterol in the treatment of both asthma and chronic obstructive pulmonary
      disease (COPD).

PMID- 23131598
TI  - The systematic development of a brief intervention to increase walking in the
      general public using an "extended" theory of planned behavior.
AB  - The Theory of Planned Behavior (TPB) has been extensively used in predictive
      studies, but there have been considerably fewer experimental tests of the theory.
      One reason for this is that the guidance on developing concrete intervention
      strategies from the abstract theory is vague, and there are few exemplars of how
      to do this. The aim of this article is to provide such an exemplar. The
      development of an intervention to increase walking in the general public is
      described, based on the TPB, extended to include postvolitional processes.
      Identification of target constructs, elicitation of key salient beliefs
      underpinning these constructs, selection of appropriate behavior change
      techniques, and technique refinement. Each step is based on available evidence
      and consistent with theory. Perceived behavioral control (PBC) was identified as
      the key determinant of walking intentions, with an "intention-behavior gap"
      noted. A brief intervention was developed, using techniques to increase PBC by
      rehearsal of previous successful performance of behavior, along with planning
      techniques to translate motivation into behavior. This systematic approach taken
      should provide a model for others. The intervention has demonstrated efficacy in
      producing large changes in objectively measured walking behavior, in 2 separate
      evaluations reported elsewhere. 

PMID- 23131599
TI  - Datasets for special series on cognitive reserve.

PMID- 23131600
TI  - Cognitive activities during adulthood are more important than education in
      building reserve.
AB  - Cognitive reserve is thought to reflect life experiences. Which experiences
      contribute to reserve and their relative importance is not understood. Subjects
      were 652 autopsied cases from the Rush Memory and Aging Project and the Religious
      Orders Study. Reserve was defined as the residual variance of the regressions of
      cognitive factors on brain pathology and was captured in a latent variable that
      was regressed on potential determinants of reserve. Neuropathology variables
      included Alzheimer's disease markers, Lewy bodies, infarcts, microinfarcts, and
      brain weight. Cognition was measured with six cognitive domain scores.
      Determinants of reserve were socioeconomic status (SES), education, leisure
      cognitive activities at age 40 (CA40) and at study enrollment (CAbaseline) in
      late life. The four exogenous predictors of reserve were weakly to moderately
      inter-correlated. In a multivariate model, all except SES had statistically
      significant effects on Reserve, the strongest of which were CA40 (beta = .31) and
      CAbaseline (beta = .28). The Education effect was negative in the full model
      (beta = -.25). Results suggest that leisure cognitive activities throughout
      adulthood are more important than education in determining reserve. Discrepancies
      between cognitive activity and education may be informative in estimating late
      life reserve.

PMID- 23131605
TI  - Juvenile oral lichen planus: a clinical rarity.

PMID- 23131601
TI  - Explaining differences in episodic memory performance among older African
      Americans and Whites: the roles of factors related to cognitive reserve and test
      bias.
AB  - Older African Americans tend to perform poorly in comparison with older Whites on
      episodic memory tests. Observed group differences may reflect some combination of
      biological differences, measurement bias, and other confounding factors that
      differ across groups. Cognitive reserve refers to the hypothesis that factors,
      such as years of education, cognitive activity, and socioeconomic status, promote
      brain resilience in the face of pathological threats to brain integrity in late
      life. Educational quality, measured by reading test performance, has been
      postulated as an important aspect of cognitive reserve. Previous studies have not
      concurrently evaluated test bias and other explanations for observed differences
      between older African Americans and Whites. We combined data from two studies to
      address this question. We analyzed data from 273 African American and 720 White
      older adults. We assessed DIF using an item response theory/ordinal logistic
      regression approach. DIF and factors associated with cognitive reserve did not
      explain the relationship between race, and age- and sex-adjusted episodic memory
      test performance. However, reading level did explain this relationship. The
      results reinforce the importance of considering education quality, as measured by
      reading level, when assessing cognition among diverse older adults.

PMID- 23131606
TI  - Repeated exposure to modern volatile anaesthetics may cause chronic hepatitis as
      well as acute liver injury.
AB  - Volatile anaesthetic agents are known to cause acute hepatitis and fulminant
      hepatic failure in susceptible individuals. Four patients were identified with
      prolonged liver injury due to volatile anaesthetic-induced hepatitis. Three had
      liver biopsy confirmation and all gave blood for specific diagnostic tests (TFA
      and CYP 2E1 IgG4 antibodies). The Roussel Uclaf Causality Assessment Method
      (RUCAM) drug causality scale was used to determine the likelihood of volatile
      anaesthetics causing the chronic liver injury. We describe four cases of volatile
      anaesthetic hepatitis in which three evolved into chronic hepatitis. The fourth
      followed a more typical pattern of acute hepatitis; however, resolution took a
      few months. These cases all occurred with modern volatile anaesthetics,
      predominantly sevoflurane, and all cases were proven with specific antibody
      tests, liver histology and a drug causality scale. This is the first report of
      chronic liver injury due to volatile anaesthetic exposure.

PMID- 23131607
TI  - Acute Sheehan's syndrome presenting as central diabetes insipidus.
AB  - Sheehan's syndrome occurs as a result of ischaemic pituitary necrosis due to
      severe postpartum haemorrhage. Improvements in obstetrical care have
      significantly reduced its incidence in developed countries, but postpartum
      pituitary infarction remains a common cause of hypopituitarism in developing
      countries. We report a case of severe postpartum haemorrhage followed by
      headache, central diabetes insipidus and failure to lactate, which prompted us to
      investigate and identify both anterior and posterior pituitary deficiency
      compatible with Sheehan's syndrome. A timely diagnosis allowed us to implement an
      adequate treatment and follow-up plan, which are known to improve clinical status
      and patient outcome.

PMID- 23131608
TI  - Ottelione A inhibited proliferation of Ehrlich ascites carcinoma cells in mice.
AB  - While the main target of chemotherapy in cancer treatment is the induction of
      apoptosis and cell death, natural products provide a wealth to medicine and are
      considered great sources of new drugs for cancer treatment. We aimed to determine
      the antitumor effect of ottelione A (OTTE) on the growth and proliferation of
      Ehrlich ascites carcinoma cells (EACs) implanted i.p. in female mice. Animals
      were inoculated with EAC cells to serve as the control group. In the OTTE group,
      animals were implanted with EAC followed by i.p. administration of OTTE.
      Antitumor activity was evaluated 15days after tumor implantation. The
      administration of OTTE significantly reduced ascetic volume, viability of EAC
      cells and increased the survival of tumor-bearing animals. Flow cytometric
      analysis indicated that OTTE induced G(0)/G(1) cell cycle arrest and apoptosis.
      These findings were associated with an alteration of redox state of EAC cells,
      which might impact cascade effects leading to cell cycle arrest at G(0)/G(1)
      phase. These effects include a decreased expression of cyclin D1, increased p53
      expression and down-regulation of rRNA level, stimulation of CD8+ infiltrating T
      lymphocytes. In addition, OTTE normalized oxidative stress in the liver of mice
      bearing EAC cells evidenced by increased the levels of glutathione, superoxide
      dismutase, and catalase. In conclusion, the differential expression of p53,
      cyclin D1, and rRNA in EAC cells as well as the infiltration of CD8+ after OTTE
      treatment may play critical roles in the G(0)/G(1) cell cycle arrest that blocks
      cell proliferation and induce apoptosis of cancer cells. The potent antitumor
      property of the ottelione A can be exploited further to develop therapeutic
      protocols for treatment of cancer.

PMID- 23131609
TI  - Enantioselective biodegradation of pharmaceuticals, alprenolol and propranolol,
      by an activated sludge inoculum.
AB  - Biodegradation of chiral pharmaceuticals in the environment can be
      enantioselective. Thus quantification of enantiomeric fractions during the
      biodegradation process is crucial for assessing the fate of chiral pollutants.
      This work presents the biodegradation of alprenolol and propranolol using an
      activated sludge inoculum, monitored by a validated enantioselective HPLC method
      with fluorescence detection. The enantioseparation was optimized using a
      vancomycin-based chiral stationary phase under polar ionic mode. The method was
      validated using a minimal salts medium inoculated with activated sludge as
      matrix. The method was selective and linear in the range of 10-800 ng/ml, with a
      R2>0.99. The accuracy ranged from 85.0 percent to 103 percent, the recovery
      ranged from 79.9 percent to 103 percent, and the precision measured by the
      relative standard deviation (RSD) was <7.18 percent for intra-batch and <5.39
      percent for inter-batch assays. The limits of quantification and detection for
      all enantiomers were 10 ng/ml and 2.5 ng/ml, respectively. The method was
      successfully applied to follow the biodegradation of the target pharmaceuticals
      using an activated sludge inoculum during a fifteen days assay. The results
      indicated slightly higher biodegradation rates for the S-enantiomeric forms of
      both beta-blockers. The presence of another carbon source maintained the
      enantioselective degradation pattern while enhancing biodegradation extent up to
      fourteen percent.

PMID- 23131611
TI  - Protective effects of Shichimotsu-koka-To on irreversible Thy-1 nephritis.
AB  - Oxidative stress and peritubular capillary (PTC) injury are involved in the
      progression of chronic kidney disease (CKD). We investigated protective effects
      of Shichimotsu-koka-To (SKT), a Japanese traditional Kampo prescription, against
      nephrosclerosis and hypertension on a CKD model due to irreversible nephritis.
      Six-week-old male Wistar rats were subjected to uninephrectomy, and to injection
      of rabbit anti-thymocyte serum. SKT treatment was continued for 15 weeks, blood
      pressure was measured, and then renal specimens were collected. PTC networks were
      detected by immunostaining for CD-31. And superoxide dismutase (SOD)-like
      activity in the tissue was evaluated. Blood pressure in the SKT group, as well as
      sham group, was significantly lower than with the vehicle. SKT markedly
      ameliorated renal function, which was evaluated with urea nitrogen clearance.
      Compared with the vehicle, SKT treatment lowered both the glomerular enlargement
      and hyper-cellularity by 80%, and decreased the extracellular matrix area by 75%.
      SKT treatment also suppressed tubular injury, and maintained PTC networks.
      Furthermore, SKT recovered SOD-like activity to the basal levels. These results
      suggest that SKT may be useful for the treatment of CKD during the progression to
      nephrosclerosis, through the mechanisms of anti-oxidative activity and
      maintenance of PTC networks.

PMID- 23131610
TI  - The pathogenesis of systemic lupus erythematosus-an update.
AB  - Systemic lupus erythematosus (SLE, lupus) is characterized by a global loss of
      self-tolerance with activation of autoreactive T and B cells leading to
      production of pathogenic autoantibodies and tissue injury. Innate immune
      mechanisms are necessary for the aberrant adaptive immune responses in SLE.
      Recent advances in basic and clinical biology have shed new light on disease
      mechanisms in lupus, with this review discussing the recent studies that offer
      valuable insights into disease-specific therapeutic targets.

PMID- 23131612
TI  - Differential brain response to alcohol cue distractors across stages of alcohol
      dependence.
AB  - Altered attention to alcohol-related cues is implicated in the craving and
      relapse cycle characteristic of alcohol dependence (ALC). Prior cue reactivity
      studies typically invoke explicit attention to alcohol cues, so the neural
      response underlying incidental cue exposure remains unclear. Here, we embed
      infrequent, task-irrelevant alcohol and non-alcohol cues in an attention
      demanding task, enabling evaluation of brain responses to distracting alcohol
      cues. Alcohol dependent individuals, across illness phase (n=44), and controls
      (n=20) performed a cue-reactivity fMRI target detection task. Significant Group
      by-Distractor effects were observed in dorsal anterior cingulate cortex (ACC),
      inferior parietal lobule, and amygdala. Controls and long-term abstainers
      increased recruitment of attention and cognitive control regions, while recent
      and long-term abstainers decreased limbic recruitment to alcohol distractors.
      Across phases of ALC, self-reported craving positively correlated with cue
      related activations in ventral ACC, medial prefrontal cortex, and cerebellum.
      Results indicate that brain responses elicited by incidental alcohol cues
      differentiate phases of ALC.

PMID- 23131613
TI  - Hormonal contraception use alters stress responses and emotional memory.
AB  - Emotionally arousing material is typically better remembered than neutral
      material. Since norepinephrine and cortisol interact to modulate emotional
      memory, sex-related influences on stress responses may be related to sex
      differences in emotional memory. Two groups of healthy women - one naturally
      cycling (NC women, n=42) and one using hormonal contraceptives (HC women, n=36) -
      viewed emotionally arousing and neutral images. Immediately after, they were
      assigned to Cold Pressor Stress (CPS) or a control procedure. One week later,
      participants received a surprise free recall test. Saliva samples were collected
      and later assayed for salivary alpha-amylase (biomarker for norepinephrine) and
      cortisol. Compared to NC women, HC women exhibited significantly blunted stress
      hormone responses to the images and CPS. Recall of emotional images differed
      between HC and NC women depending on noradrenergic and cortisol responses. These
      findings may have important implications for understanding the neurobiology of
      emotional memory disorders, especially those that disproportionately affect
      women.

PMID- 23131614
TI  - beta-Adrenergic blockade during reactivation reduces the subjective feeling of
      remembering associated with emotional episodic memories.
AB  - In contrast to neutral events, emotionally arousing events often are remembered
      vividly and with great detail. Although generally adaptive to survival, this
      emotional memory enhancement may contribute to psychopathology. Blocking the
      arousal-related noradrenergic activity with a beta blocker shortly after learning
      prevents the emotional enhancement of memory. In the present experiment, we
      tested in 48 healthy subjects whether the administration of the beta blocker
      propranolol before the reactivation of already consolidated emotional episodic
      memories may interfere with their reconsolidation and, thus, reduce the
      subsequent feeling of remembering associated with these memories. Our results
      show that propranolol before reactivation abolished the superior memory for
      emotional relative to neutral stimuli and decreased 'remember' judgments for
      emotional items, suggesting that beta-adrenergic blockade during reactivation
      made emotional memories comparable to neutral memories.

PMID- 23131615
TI  - Category effects: is top-down control alone sufficient to elicit the mismatch
      negativity (MMN) component?
AB  - This study investigated whether the mismatch negativity (MMN) event-related brain
      potential (ERP) could be evoked by purely top-down, attentional control. An
      infrequently occurring tone was designated as a target prior to presenting a
      randomized sequence of five equi-probably occurring tones. MMN elicitation to the
      tones categorized as "high", "medium", or "low" frequency, and designated as the
      target, would indicate that the change detection process can be driven solely by
      top-down control. However, MMNs were not elicited by the categorized tones. Only
      the N2b and P3b attention-driven target detection components were elicited. These
      results suggest that top-down factors alone cannot generate mismatch negativity.
      Standard formation by stimulus-driven factors is required.

PMID- 23131616
TI  - N170 response to facial expressions is modulated by the affective congruency
      between the emotional expression and preceding affective picture.
AB  - Does contextual affective information influence the processing of facial
      expressions already at the relatively early stages of face processing? We
      measured event-related brain potentials to happy and sad facial expressions
      primed by preceding pictures with affectively positive and negative scenes. The
      face-sensitive N170 response amplitudes showed a clear affective priming effect:
      N170 amplitudes to happy faces were larger when presented after positive vs.
      negative primes, whereas the N170 amplitudes to sad faces were larger when
      presented after negative vs. positive primes. Priming effects were also observed
      on later brain responses. The results support an early integration in processing
      of contextual and facial affective information. The results also provide
      neurophysiological support for theories suggesting that behavioral affective
      priming effects are based, at least in part, on facilitation of encoding of
      incoming affective information.

PMID- 23131617
TI  - No effect of trait anxiety on differential fear conditioning or fear
      generalization.
AB  - Previous studies have shown that individuals with anxiety disorders exhibit
      deficits in fear inhibition and excessive generalization of fear, but little data
      exist on individuals at risk from these disorders. The present study examined the
      role of trait anxiety in the acquisition and generalization of fear in 126
      healthy participants selected on the basis of their trait-anxiety scores.
      Measures of conditioning included fear-potentiated startle, skin conductance
      response and online risk ratings for the unconditioned stimulus. Contrary to our
      hypotheses, trait anxiety did not have any effect either on the acquisition or
      the generalization of fear. Our results suggest that these fear conditioning
      processes are not impaired in individuals at risk from anxiety.

PMID- 23131618
TI  - Simultaneous co-metabolic decolourisation of azo dye mixtures and bio-electricity
      generation under thermophillic (50  degrees C) and saline conditions by an
      adapted anaerobic mixed culture in microbial fuel cells.
AB  - In this study, azo dye adapted mixed microbial consortium was used to effectively
      remove colour from azo dye mixtures and to simultaneously generate bio
      electricity using microbial fuel cells (MFCs). Operating temperature (20-50 
      degrees C) and salinity (0.5-2.5%w/v) were varied during experiments. Reactor
      operation at 50  degrees C improved dye decolourisation and COD removal kinetic
      constants by approximately 2-fold compared to the kinetic constants at 30 
      degrees C. Decolourisation and COD removal kinetic constants remained high (0.28
      h(-1) and 0.064 h(-1) respectively) at moderate salinity (1%w/v) but deteriorated
      approximately 4-fold when the salinity was raised to 2.5% (w/v). Molecular
      phylogenetic analysis of microbial cultures used in the study indicated that both
      un-acclimated and dye acclimated cultures from MFCs were predominantly comprised
      of Firmicutes bacteria. This study demonstrates the possibility of using adapted
      microbial consortia in MFCs for achieving efficient bio-decolourisation of
      complex azo dye mixtures and concomitant bio-electricity generation under
      industrially relevant conditions.

PMID- 23131619
TI  - Comparison of the impact of ionic liquid pretreatment on recalcitrance of agave
      bagasse and switchgrass.
AB  - Lignocellulose represents a sustainable source of carbon for transformation into
      biofuels. Effective biomass to sugar conversion strategies are needed to lower
      processing cost without degradation of polysaccharides. Since ionic liquids (ILs)
      are excellent solvents for pretreatment/dissolution of biomass, IL pretreatment
      was carried out on agave bagasse (AGB-byproduct of tequila industry) and
      digestibility and sugar yield was compared with that obtained with switchgrass
      (SWG). The IL pretreatment was conducted using ([C2mim][OAc]) at 120 and 160 
      degrees C for 3h and 15% biomass loading. While pretreatment using [C2mim][OAc]
      was very effective in improving the digestibility of both feedstocks, IL
      pretreatment at 160  degrees C resulted in higher delignification for AGB (45.5%)
      than for SWG (38.4%) when compared to 120  degrees C (AGB-16.6%, SWG-8.2%),
      formation of a highly amorphous cellulose structure and a significant enhancement
      of enzyme kinetics. These results highlight the potential of AGB as a biofuel
      feedstock that can produce high sugar yields with IL pretreatment.

PMID- 23131620
TI  - Thermostability, pH stability and dye degrading activity of a bacterial laccase
      are enhanced in the presence of Cu2O nanoparticles.
AB  - The present study relates to a nanotechnology enabled method in which purified
      laccase from Escherichia coli AKL2 was supplemented with 100 MUM copper oxide
      nanoparticles (Cu(2)O) (NP-laccase). The activity, half life and stability of NP
      laccase were enhanced by 4, 42 and 36-fold respectively at high temperature (80 
      degrees C) and also over a wide range of pH (4-12) than laccase (in the presence
      of 0.18 mM CuSO(4)). Thermodynamic analysis of the nanoparticle-induced enzyme
      stability revealed an enhanced entropy-enthalpy compensation at 80  degrees C,
      which reflected the maintenance of its native structure. This was further
      supported by CD studies. The enhanced activity and thermostability of NP-laccase
      can be utilized for efficient decolorisation of dyes (both phenolic and azo).

PMID- 23131621
TI  - Pyrolysis of high-ash sewage sludge in a circulating fluidized bed reactor for
      production of liquids rich in heterocyclic nitrogenated compounds.
AB  - A circulating fluidized bed reactor was used for pyrolyzing sewage sludge with a
      high ash content to produce liquids rich in heterocyclic nitrogenated compounds.
      GC/MS and FTIR analyses showed that heterocyclic nitrogenated compounds and
      hydrocarbons made up 38.5-61.21% and 2.24-17.48% of the pyrolysis liquids,
      respectively. A fluidized gas velocity of 1.13 m/s, a sludge feed rate of 10.78
      kg/h and a particle size of 1-2mm promoted heterocyclic nitrogenated compound
      production. Utilizing heterocyclic nitrogenated compounds as chemical feedstock
      could be a way for offsetting the cost of sewage sludge treatment.

PMID- 23131622
TI  - Synergism of Pseudomonas aeruginosa and Fe0 for treatment of heavy metal
      contaminated effluents using small scale laboratory reactor.
AB  - In this study Pseudomonas aeruginosa a metal tolerant strain was not only applied
      for heavy metal removal but also to the solublization performance of the
      precipitated metal ions during effluent treatment. The synergistic effect of the
      isolate and Fe(0) enhanced the metal removal potential to 72.97% and 87.63% for
      Cr(VI) and cadmium, respectively. The decrease in cadmium ion removal to 43.65%
      (aeration+stirring reactors), 21.33% (aerated reactors), and 18.95% (without
      aerated+without stirring) with an increase in incubation period not only indicate
      the presence of soluble less toxic complexes, but also help in exploration of the
      balancing potential for valuable metal recovery. A relatively best fit and
      significant values of the correlation coefficient 0.912, 0.959, and 0.9314 for
      mixed effluent (Paint Industry effluent+CETP Wazirpur, effluent), CETP, Wazirpur,
      and control effluents, respectively, indicating first-order formulation and
      provide a reasonable description of COD kinetic data.

PMID- 23131623
TI  - A combined process of activated carbon adsorption, ion exchange resin treatment
      and membrane concentration for recovery of dissolved organics in pre-hydrolysis
      liquor of the kraft-based dissolving pulp production process.
AB  - To recover dissolved organics in pre-hydrolysis liquor (PHL) of the kraft-based
      dissolving pulp production process, a new combined process concept of sequential
      steps of activated carbon adsorption, ion exchange resin treatment, and membrane
      concentration, was proposed. The removal of lignin in the PHL was achieved in the
      activated carbon adsorption step, which also facilitates the subsequent
      operations, such as the membrane filtration and ion exchange resin treatment. The
      ion exchange resin treatment resulted in the removal/concentration of acetic
      acid, which opens the door for acetic acid recovery. The membrane filtration is
      to recover/concentrate the dissolved sugars. The combined process resulted in the
      production of PHL-based concentrate with relatively high concentration of
      hemicellulosic sugars, i.e., 22.13%.

PMID- 23131624
TI  - Fabrication, characterization and application of nitrogen-containing carbon
      nanospheres obtained by pyrolysis of lignosulfonate/poly(2-ethylaniline).
AB  - Lignosulfonate/poly(2-ethylaniline) (LS-PEA) composite nanospheres were prepared
      via in situ polymerization of 2-ethylaniline (EA) with lignosulfonate (LS) as a
      dispersant. LS-PEA nanospheres with an average diameter of 155 nm were obtained
      at an optimal LS concentration of 20 wt.%. Subsequently, nitrogen-containing
      carbon nanospheres were fabricated via direct pyrolysis of the LS-PEA composite
      nanospheres at 600-800  degrees C. The carbon nanospheres prepared by pyrolysis
      were used as anodes of lithium-ion batteries. The first charge and discharge
      capacity of carbon nanospheres prepared at 700  degrees C at current densities of
      60 and 100 mA g(-1) were 980 and 432 mAh g(-1), and 764 and 342 mAh g(-1),
      respectively. The batteries still owned a high capacity of 353 and 296 mAh g(-1)
      after 20 cycles. The results indicated that these nitrogen-containing carbon
      nanospheres could be used as a promising candidate for electrode materials of
      lithium-ion batteries.

PMID- 23131625
TI  - Catalytic hydrothermal gasification of algae for hydrogen production: composition
      of reaction products and potential for nutrient recycling.
AB  - Chlorella vulgaris, Spirulina platensis and Saccharina latissima were processed
      under supercritical water gasification conditions at 500  degrees C, 36 MPa in an
      Inconel batch reactor for 30 min in the presence/absence of NaOH and/or Ni
      Al(2)O(3). Hydrogen gas yields were more than two times higher in the presence of
      NaOH than in its absence and tar yields were reduced by up to 71%. Saccharina, a
      carbohydrate-rich macro-alga, gave the highest hydrogen gas yields of 15.1
      mol/kg. The tars from all three algae contained aromatic compounds, including
      phenols, alkyl benzenes and polycyclic aromatic hydrocarbons as well as
      heterocyclic nitrogen compounds. Tars from Chlorella and Spirulina contained high
      yields of pyridines, pyrroles, indoles and pyrimidines. Up to 97% TOC removal
      were achieved in the process waters from the gasification of the algae. Analyses
      for specific nutrients in the process waters indicated that the process waters
      from Saccharina could potentially be used for microalgae cultivation.

PMID- 23131626
TI  - Life cycle assessment of two emerging sewage sludge-to-energy systems: evaluating
      energy and greenhouse gas emissions implications.
AB  - A "cradle-to-grave" life cycle assessment was conducted to examine the energy and
      greenhouse gas (GHG) emission footprints of two emerging sludge-to-energy
      systems. One system employs a combination of anaerobic digestion (AD) and fast
      pyrolysis for bioenergy conversion, while the other excludes AD. Each system was
      divided into five process phases: plant construction, sludge pretreatment, sludge
      to-bioenergy conversion, bioenergy utilizations and biochar management. Both
      systems achieved energy and GHG emission benefits, and the AD-involving system
      performed better than the AD-excluding system (5.30 vs. 0.63 GJ/t sludge in net
      energy gain and 0.63 vs. 0.47 t CO(2)eq/t sludge in emission credit for base
      case). Detailed contribution and sensitivity analyses were conducted to identify
      how and to what degree the different life-cycle phases are responsible for the
      energy and emission impacts. The energy and emission performances were
      significantly affected by variations in bioenergy production, energy requirement
      for sludge drying and end use of bioenergy.

PMID- 23131627
TI  - Catalyzed modified clean fractionation of switchgrass.
AB  - Switchgrass was used as a lignocellulosic feedstock for second generation ethanol
      production, after pretreatment using sulfuric acid-catalyzed modified clean
      fractionation based on NREL's (National Renewable Energy Laboratory) original
      procedure. Optimization of temperature, catalyst concentration and solvent
      composition was performed using Response Surface Methodology, and 59.03 +/- 7.01%
      lignin recovery, 84.85 +/- 1.34% glucose, and 44.11 +/- 3.44% aqueous fraction
      xylose yields were obtained at 140.00  degrees C, 0.46% w/w catalyst
      concentration, 36.71% w/w ethyl acetate concentration, and 25.00% w/w ethanol
      concentration. The cellulose fraction did not inhibit the fermentation
      performance of Saccharomyces cerevisiae and resulted in an ethanol yield of 89.60
      +/- 2.1%.

PMID- 23131628
TI  - Ultrasonication-assisted manufacture of cellulose nanocrystals esterified with
      acetic acid.
AB  - Esterified cellulose nanocrystals (E-CNCs) are cellulose derivatives that could
      be applied in biomedical and chemical industries. E-CNCs were prepared with
      cellulose pulp using a mixture of 17.5M acetic and 18.4M sulfuric acid with the
      aid of ultrasonication. The effects of esterification time (3-7h),
      ultrasonication time (with a frequency of 40 kHz, 0 to 6h) and temperature (68-75
      degrees C) on the yield and degree of substitution (DS) of E-CNCs were
      evaluated. The sample obtained without ultrasonication had the lowest yield and
      DS value of 48.16% and 0.22, respectively, whereas ultrasonication for 5h at 70 
      degrees C resulted in a yield of 85.38% and a DS value of 0.46. Characterization
      indicated the successful esterification of hydroxyl groups of cellulose, and the
      width of rod-shaped E-CNCs was from 10 to 100 nm. The study provides a simple and
      convenient method to manufacture E-CNCs.

PMID- 23131629
TI  - Fluoride adsorption on carboxylated aerobic granules containing Ce(III).
AB  - Aerobic granules (AG) were carboxylated and Ce(III) was incorporated to obtain
      modified granuels (Ce(III)-MAG) for removal of fluoride from aqueous solutions.
      The Ce(III)-MAG was characterized by SEM, FTIR, XRD and pH(pzc), and the
      introduction of carboxyl groups and Ce(III) was confirmed. The adsorption
      capacity of Ce(III)-MAG for fluoride was 45.80 mg/g at neutral pH, an increase of
      359% compared to the capacity of pristine AG. Adsorption was highest at pH range
      of 3.0-5.0. A positive effect on fluoride removal in the order of K(+) ~ Mg(2+) >
      Ca(2+) > Na(+) and a negative effect in the order of NO(3)(-) > Cl(-) > SO(4)(2-)
      > HCO(3)(-) > PO(4)(3-) was observed. Fluoride adsorption followed the Redlich
      Peterson model and the pseudo-first order model with correlation factors of 0.999
      and 0.950, respectively. Ce(III)-MAG held up to 790 bed volumes and the effluent
      fluoride concentration remained below 1.0mg/L (influent fluoride 10mg/L).

PMID- 23131630
TI  - Optimization of microwave-assisted calcium chloride pretreatment of corn stover.
AB  - A 62.5% (w/w) CaCl(2) solution was used in the microwave pretreatment of corn
      stover. The central composite design (CCD) of response surface methodology (RSM)
      was employed to design and optimize the CaCl(2)-assisted microwave pretreatment
      (CaCl(2)-pretreatment). Temperature and time were the main factors affecting the
      enzymatic digestibility of corn stover. After CaCl(2)-pretreatment, hemicellulose
      degradation reached 85.90%, the specific surface area (SSA) increased by 168.93%,
      cellulose crystallinity index (CrI) decreased by 13.91% compared to untreated
      corn stover. The optimal conditions for glucose production with the CaCl(2)
      pretreatment obtained by CCD were, 162.1  degrees C, 12 min and solid-to-liquid
      ratio 10% (w/v). Under these conditions, the enzymatic hydrolysis ratio of
      cellulose was 90.66% and glucose recovery was 65.47%. This novel process achieved
      the temperature of about 160  degrees C necessary for lignocellulose pretreatment
      under atmospheric pressure using the cheap calcium chloride as the heating
      medium.

PMID- 23131631
TI  - Ethanol production from Saccharina japonica using an optimized extremely low acid
      pretreatment followed by simultaneous saccharification and fermentation.
AB  - An extremely low acid (ELA) pretreatment using 0.06% (w/w) sulfuric acid at 170 
      degrees C for 15 min was employed to extract non-glucan components from
      Saccharina japonica, a brown macroalgae. Subsequent simultaneous saccharification
      and fermentation (SSF) was conducted using Saccharomyces cerevisiae DK 410362 and
      cellulase (15 FPU/g-glucan) and beta-glucosidase (70 pNPGU/g-glucan). Deionized
      water was used for making fermentation suspension. After the ELA pretreatment, a
      glucan content of 29.10% and an enzymatic digestibility of 83.96% was obtained
      for pretreated S. japonica. These values are 4.2- and 2.4-fold higher,
      respectively, than those of obtained with untreated S. japonica. In SSF, a
      bioethanol concentration of 6.65 g/L was obtained, corresponding to a glucose
      equivalent concentration of 13.01 g/L, which indicated an SSF yield of 67.41%
      based on the total available glucan of the pretreated S. japonica. The remaining
      separated liquid hydrolysate, which contains mannitol and alginate-derived
      oligosaccharides can be applied to other fermentations.

PMID- 23131632
TI  - Effect of long-term starvation conditions on polyphosphate- and glycogen
      accumulating organisms.
AB  - Endogenous processes such as biomass decay and intracellular polymers degradation
      of polyphosphate-accumulating organisms (PAOs) and glycogen-accumulating
      organisms (GAOs) were investigated. Cultures enriched in Accumulibacter (a well
      known PAO) or Competibacter (a well known GAO) were subjected to 21 and 26 days
      of alternating anaerobic/aerobic conditions respectively. The main energy source
      for PAOs during starvation was their intracellular polyphosphate released into
      the medium during the first 14 days of starvation. In contrast, GAOs used their
      intracellular glycogen during the 26 days of starvation. Biomass decay rates were
      0.029 d(-1) for PAOs and almost negligible for GAOs. The reduction in acetate
      uptake rate during the starvation period, referred to as activity decay, was 0.25
      and 0.047 d(-1) for PAOs and GAOs, respectively. Once wastewater was
      reintroduced, both populations recovered their initial substrate uptake rate
      after 1 day. The results obtained show that PAOs are more affected than GAOs by
      starvation conditions.

PMID- 23131633
TI  - Separation and characterization of cellulose fibers from cypress wood treated
      with ionic liquid prior to laccase treatment.
AB  - Separation of cellulose fibers (CFs) from woody biomass with minimal structural
      alteration using a "green" and efficient method was achieved by treatment with
      the ionic liquid (IL), [emim][OAc] (1-ethyl-3-methylimidazolium acetate) at 80 
      degrees C for 1h. The IL was recovered by rinsing with water-acetone mixture
      prior to treatment of the wood with Trametes sp. laccase in the presence of 1
      hydroxybenzotriazole as a mediator. IL pretreatment did not significantly change
      the chemical composition of the wood, but did alter its structure and rendered
      its surface more accessible to the enzyme. Treated and untreated samples were
      characterized by SEM, FTIR, XRD, TGA, and chemical methods. The cellulose content
      of the produced fibers was approximately 73.1% and the lignin content was 9.8%,
      much lower than the lignin content of 29.3% of the untreated wood. The cellulose
      fibers exhibited higher cellulose crystallinity and better thermal stability
      compared to untreated wood materials.

PMID- 23131634
TI  - Comparison in performance of sediment microbial fuel cells according to depth of
      embedded anode.
AB  - Five rigid graphite plates were embedded in evenly divided sections of sediment,
      ranging from 2 cm (A1) to 10 cm (A5) below the top sediment layer. The maximum
      power and current of the MFCs increased in depth order; however, despite the
      increase in the internal resistance, the power and current density of the A5 MFC
      were 2.2 and 3.5 times higher, respectively, than those of the A1 MFC. In
      addition, the anode open circuit potentials (OCPs) of the sediment microbial fuel
      cells (SMFCs) became more negative with sediment depth. Based on these results,
      it could be then concluded that as the anode-embedding depth increases, that the
      anode environment is thermodynamically and kinetically favorable to anodophiles
      or electrophiles. Therefore, the anode-embedding depth should be considered an
      important parameter that determines the performance of SMFCs, and we posit that
      the anode potential could be one indicator for selecting the anode-embedding
      depth.

PMID- 23131635
TI  - Anaerobic methane production from five common grassland species at sequential
      stages of maturity.
AB  - Since grass will likely be a dominant feedstock for on-farm anaerobic digestion
      in Northwest Europe, changes in the chemical composition of five common grass
      species with advancing harvest date in the primary growth were investigated and
      related to specific CH(4) yields. The increase in fibre components with advancing
      harvest date had a negative impact on the specific CH(4) yield (253 and 225 Nl
      CH(4) kg(-1) VS for 12 May and 7 July harvests, respectively), and this impact
      was similar across the five grass species. At common growth stages, only small
      differences in herbage digestibility was observed between the grass species and
      this was reflected in similar specific CH(4) yields; however, the 26% lower area
      specific CH(4) yield of the cocksfoot variety (Dactylis glomerata L. var. Pizza)
      would make it the most expensive of the five grass species to produce and the
      least suitable for anaerobic digestion.

PMID- 23131636
TI  - Enrichment and characterization of a bacteria consortium capable of heterotrophic
      nitrification and aerobic denitrification at low temperature.
AB  - Nitrogen removal in wastewater treatment plants is usually severely inhibited
      under cold temperature. The present study proposes bioaugmentation using
      psychrotolerant heterotrophic nitrification-aerobic denitrification consortium to
      enhance nitrogen removal at low temperature. A functional consortium has been
      successfully enriched by stepped increase in DO concentration. Using this
      consortium, the specific removal rates of ammonia and nitrate at 10  degrees C
      reached as high as 3.1 mg N/(gSSh) and 9.6 mg N/(gSSh), respectively. PCR-DGGE
      and clone library analysis both indicated a significant reduction in bacterial
      diversity during enrichment. Phylogenetic analysis based on nearly full-length
      16S rRNA genes showed that Alphaproteobacteria, Deltaproteobacteria and
      particularly Bacteroidetes declined while Gammaproteobacteria (all clustered into
      Pseudomonas sp.) and Betaproteobacteria (mainly Rhodoferax ferrireducens) became
      dominant in the enriched consortium. It is likely that Pseudomonas spp. played a
      major role in nitrification and denitrification, while R. ferrireducens and its
      relatives utilized nitrate as both electron acceptor and nitrogen source.

PMID- 23131637
TI  - Investigation of microwave dielectric properties of biodiesel components.
AB  - Advanced microwave technology has the potential to significantly enhance the
      biodiesel production process. Knowledge of dielectric properties of materials
      plays a major role in microwave design for any process. Dielectric properties
      (epsilon' and epsilon") of biodiesel precursors: soybean oil, alcohols and
      catalyst and their different mixtures were measured using a vector network
      analyzer and a slim probe in an open ended coaxial probe method at four different
      temperatures (30, 45, 60 and 75  degrees C) and in the frequency range of 280 MHz
      to 4.5 GHz. Results indicate that the microwave dielectric properties depend
      significantly on both temperature and frequency. Addition of catalyst
      significantly affected the dielectric properties. Dielectric properties behaved
      differently when oil, alcohol and catalyst was mixed at room temperature before
      heating and when the oil and the alcohol catalyst mixture was heated separately
      to a pre-determined temperature before mixing. These results can be used in
      designing microwave based transesterification system.

PMID- 23131638
TI  - Silver-embedded modified hyperbranched epoxy/clay nanocomposites as antibacterial
      materials.
AB  - Silver-embedded modified hyperbranched epoxy/clay nanocomposites were prepared at
      different wt.% of octadecyl amine-modified montmorillonite at a constant silver
      concentration (1 wt.%). UV-visible, XRD and TEM studies confirmed the formation
      of silver nanoparticles. Compared to the system without silver and clay, the
      gloss from 70 degrees  to 94 degrees , scratch hardness from 4 to 5.8 kg, impact
      strength from 60 to 90 cm, tensile strength from 8.5 to 15.5 MPa, adhesive
      strength from 5 to 7.1 * 10(9)N/m, flexibility from >6 to <4mm, and
      thermostability from 230 to 260  degrees C increased for the modified system.
      Resistance to aqueous 10% HCl, 0.5% NaOH, 10% NaCl also increased. The
      nanocomposites showed antibacterial activity in well diffusion assays against
      Staphylococcus aureus (ATCC11632), Bacillus subtilis (ATCC11774), Escherichia
      coli (MTCC40), Pseudomonas aeruginosa (MTCC7814) and Klebsiella pneumoniae
      (ATCC10031). The results showed that these nanocomposites have potential to be
      used as antimicrobial materials.

PMID- 23131639
TI  - Characterization of aerobic granular sludge treating high strength agro-based
      wastewater at different volumetric loadings.
AB  - Understanding the relationship between microbial community and mechanism of
      aerobic granulation could enable wider applications of granules for high-strength
      wastewater treatment. The majority of granulation studies principally determine
      the engineering aspects of granules formation with little emphasis on the
      microbial diversity. In this study, three identical reactors namely R1, R2 and R3
      were operated using POME at volumetric loadings of 1.5, 2.5 and 3.5 kg COD m(-3)
      d(-1), respectively. Aeration was provided at a volumetric flow rate of 2.5 cms(
      1). Aerobic granules were successfully developed in R2 and R3 while bioflocs
      dominated R1 until the end of experiments. Fractal dimension (D(f)) averaged at
      1.90 suggesting good compactness of granules. The PCR-DGGE results indicated
      microbial evolutionary shift throughout granulation despite different operating
      OLRs based on decreased Raup and Crick similarity indices upon mature granule
      formation. The characteristics of aerobic granules treating high strength agro
      based wastewater are determined at different volumetric loadings.

PMID- 23131640
TI  - Application of Anaerobic Digestion Model No. 1 for describing anaerobic digestion
      of grass, maize, green weed silage, and industrial glycerine.
AB  - Anaerobic digestion of organic waste plays an important role for the development
      of sustainable energy supply based on renewable resources. For further process
      optimization of anaerobic digestion, biogas production with the commonly used
      substrates, grass, maize, and green weed silage, together with industrial
      glycerine, were analyzed by the Weender analysis/van Soest method, and a
      simulation study was performed, based on the International Water Association's
      (IWA) Anaerobic Digestion Model No. 1 (ADM1). The simplex algorithm was applied
      to optimize kinetic constants for disintegration and hydrolysis steps for all
      examined substrates. Consequently, new parameters were determined for each
      evaluated substrate, tested against experimental cumulative biogas production
      results, and assessed against ADM1 default values for disintegration and
      hydrolysis kinetic constants, where the ADM1 values for mesophilic high rate and
      ADM1 values for solids were used. Results of the optimization lead to a precise
      prediction of the kinetics of anaerobic degradation of complex substrates.

PMID- 23131641
TI  - Propionate addition enhances the biodegradation of the xenobiotic herbicide
      propanil and its metabolite.
AB  - This study investigated ways of stimulating the biodegradation rates of the
      commonly applied herbicide, 3,4-dichloropropionanilide (propanil), and its
      metabolite, 3,4-dichloroaniline (DCA), as well as the growth rate of propanil-
      and DCA-degrading organisms in a mixed culture. Propionate, the other metabolite
      of propanil, stimulated the specific degradation rates of both propanil and DCA
      after a brief acclimation period. A metabolic model developed to characterise the
      metabolism of propanil and DCA biodegradation showed that the efficiency of
      oxidative phosphorylation (i.e. P/O ratio), which measures the metabolic
      efficiency, increased over time by 6- to 10-fold. This increase was accompanied
      by a 5- to 10-fold increase in the propanil and DCA biodegradation degradation
      rates. The biodegradation rates of the culture were unaffected when using an
      irrigation water matrix (Tejo river, Portugal), highlighting the utility of the
      culture for bioaugmentation purposes.

PMID- 23131642
TI  - Fermentation of liquefacted hydrothermally pretreated sweet sorghum bagasse to
      ethanol at high-solids content.
AB  - The ability of sweet sorghum bagasse to be utilized as feedstock for ethanol
      production at high initial dry matter concentration was investigated. In order to
      achieve high enzymatic hydrolysis yield, a hydrothermal pretreatment prior to
      liquefaction and saccharification was applied. Response surface methodology had
      been employed in order to optimize the pretreatment step, taking into account the
      yield of cellulose hydrolysis. Liquefaction of the pretreated bagasse was
      performed at a specially designed liquefaction chamber at 50  degrees C for
      either 12 or 24h using an enzyme loading of 10 FPU/g . DM and 18% DM.
      Fermentation of liquefacted bagasse was not affected by liquefaction duration and
      leaded to an ethanol production of 41.43 g/L and a volumetric productivity of
      1.88 g/Lh. The addition of extra enzymes at the start up of SSF enhanced both
      ethanol concentration and volumetric productivity by 16% and 17% after 12 and 24h
      saccharification, respectively.

PMID- 23131643
TI  - Enhancement of lipopeptides production in a two-temperature-stage process under
      SSF conditions and its bioprocess in the fermenter.
AB  - A two-temperature-stage process was developed for the production of lipopeptides
      under SSF conditions. The effects of various temperatures, ranging from 25 to 40 
      degrees C, on the bacterial growth during the growth stage and on the production
      of lipopeptides during the productive stage were investigated. The optimum
      temperatures were found to be 30  degrees C for the growth of the strain and 37 
      degrees C for the biosynthesis of lipopeptides. The two-stage fermentation
      temperatures should be 30  degrees C in the initial 24h and then 37  degrees C
      for the enhanced production of lipopeptides. The bioprocess results obtained in a
      50 L fermenter verified the efficacy of this technique, which increased the yield
      of lipopeptides by 8.40% in flasks and by 13.11% in the fermenter, with a 4h
      decrease of fermentation time in the fermenter. The 1000-fold scale-up of
      fermentation in a fermenter was successfully achieved.

PMID- 23131644
TI  - Attached cultivation technology of microalgae for efficient biomass feedstock
      production.
AB  - The potential of microalgae biofuel has not been realized because of low
      productivity and high costs associated with the current cultivation systems. In
      this paper, an attached cultivation method was introduced, in which microalgae
      cells grew on the surface of vertical artificial supporting material to form
      algal film. Multiple of the algal films were assembled in an array fashion to
      dilute solar irradiation to facilitate high photosynthetic efficiency. Results
      showed that a broad range of microalgae species can grow with this attached
      method. A biomass productivity of 50-80 g m(-2) d(-1) was obtained outdoors for
      Scenedesmus obliquus, corresponding to the photosynthetic efficiency of 5.2-8.3%
      (total solar radiation). This attached method also offers lots of possible
      advantages over traditional open ponds, such as on water saving, harvesting,
      contamination controlling and scale-up. The attached cultivation represents a
      promising technology for economically viable production of microalgae biofuels.

PMID- 23131645
TI  - Application of microwave radiation to biofilm heating during wastewater treatment
      in trickling filters.
AB  - The purpose of this study was to demonstrate the potential for improving
      wastewater treatment by the application of microwave radiation (MW) compared to
      convective heating (CH) of trickling filters. Microwaves were delivered to the
      biofilm in a continuous and intermittent way to obtain temperatures of 20, 25, 35
      and 40  degrees C. Although there was no effect of MW on organic removal, the
      observed yield coefficient was lower during the continuous MW supply compared to
      the periodic dosage and CH. The presence of organic compounds in the influent and
      continuous biofilm exposure to MW resulted in ca. 10% higher efficiency and ca.
      20% higher rate of nitrification compared to intermittent MW dosage and CH.
      Independent of the method of reactor heating, the absence of organic carbon in
      the influent induced a significant increase in ammonium oxidation efficiency at
      20-35  degrees C. Despite the aerobic conditions in trickling filters, nitrogen
      loss was observed.

PMID- 23131646
TI  - Enzymatic analyses demonstrate thermal adaptation of alpha-glucosidase activity
      in starch amended gully waste.
AB  - In this study we investigated the effect of starch amendment on alpha-glucosidase
      activity in an organic waste environment, treated under both mesophilic and
      thermophilic conditions. The relative effects of temperature on alpha-glucosidase
      activity with regard to in situ and assay conditions were investigated under a
      reciprocal design. The decline in dry matter under the different thermal regimes
      was consistent with the temperature independent degradation of starch. The
      results of extra-cellular enzyme analysis showed a significant relationship
      between starch addition and alpha-glucosidase activity, with evidence of thermal
      adaptation to the in situ temperature. A weaker, but significant, effect of
      starch addition on beta-glucosidase activity was observed, with no evidence for
      thermal adaptation. Thus, our data is consistent with a substrate adaptive
      response to temperature, albeit under potentially a high selective pressure.

PMID- 23131647
TI  - Structural features and antioxidant activity of xylooligosaccharides
      enzymatically produced from sugarcane bagasse.
AB  - Xylooligosaccharides (XOS) were prepared from xylan-rich hemicelluloses isolated
      by potassium hydroxide from sugarcane bagasse by hydrolysis with crude xylanase
      secreted by Pichia stipitis. Hydrolysis for 12h produced XOS with a maximum yield
      of 31.8%, equivalent to 5.29 mg mL(-1) in the hydrolyzate. XOS with degrees of
      polymerization (DP) from 2 to 4 (xylobiose, xylotriose, and xylotetraose) were
      the major components in the hydrolysates, whereas the oligosaccharides with
      higher DP of 5-6 (xylopentaose and xylohexose) showed a constant low level. FT-IR
      and NMR ((1)H, (13)C, HSQC) demonstrated that XOS contained Araf and 4-O-Me-alpha
      D-GlcpA residues. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay showed that the
      XOS exhibited concentration-dependent antioxidant activity. The results obtained
      indicate that the XOS produced from sugarcane bagasse can be employed in food
      related applications.

PMID- 23131648
TI  - Biogas production from pear residues using sludge from a wastewater treatment
      plant digester. Influence of the feed delivery procedure.
AB  - Clear economic advantages may be obtained from the management of seasonal fruit
      wastes by codigestion at existing facilities which are working throughout the
      year with other residues. We have explored the biomethanization of pear residues
      in a 5L stirred reactor loaded with sludge from the anaerobic digester of a
      municipal wastewater treatment plant. Different organic loading rates (OLRs) of
      fruit waste were tested with two delivery procedures: a discontinuous one (fed
      once a day) and a pseudocontinuous one. For both procedures, as the OLR increases
      the pH of the digester drops to acidic values and large OLRs may cause the
      reactor failure. Nevertheless, the pseudocontinuous delivery allows the treatment
      of more residue, (10.5 versus 6.0 g of volatile solids per litre of reactor and
      day), maintaining the specific biogas production (0.44 L of biogas per gram of
      volatile solids), with some improvement in methane concentration (44% vs 39%).

PMID- 23131649
TI  - High efficient treatment of citric acid effluent by Chlorella vulgaris and
      potential biomass utilization.
AB  - The efficiency of treating citric acid effluent by green algae Chlorella was
      investigated. With the highest growth rate, Chlorella vulgaris C9-JN2010 that
      could efficiently remove nutrients in the citric acid effluent was selected for
      scale-up batch experiments under the optimal conditions, where its maximum
      biomass was 1.04 g l(-1) and removal efficiencies of nutrients (nitrogen,
      phosphorus, total organic carbon, chemical oxygen demand and biochemical oxygen
      demand) were above 90.0%. Algal lipid and protein contents were around 340.0 and
      500.0 mg . g(-1) of the harvested biomass, respectively. Proportions of
      polyunsaturated fatty acids in the lipids and eight kinds of essential amino
      acids in algal protein were 74.0% and 40.0%, respectively. Three major fatty
      acids were hexadecanoic acid, eicosapentaenoic acid and docosadienoic acid. This
      specific effluent treatment process could be proposed as a dual-beneficial
      approach, which converts nutrients in the high strength citric acid effluent into
      profitable byproducts and reduces the contaminations.

PMID- 23131650
TI  - End-of-life of starch-polyvinyl alcohol biopolymers.
AB  - This study presents a life cycle assessment (LCA) model comparing the waste
      management options for starch-polyvinyl alcohol (PVOH) biopolymers including
      landfill, anaerobic digestion (AD), industrial composting and home composting.
      The ranking of biological treatment routes for starch-PVOH biopolymer wastes
      depended on their chemical compositions. AD represents the optimum choice for
      starch-PVOH biopolymer containing N and S elements in global warming potential
      (GWP(100)), acidification and eutrophication but not on the remaining impact
      categories, where home composting was shown to be a better option due to its low
      energy and resource inputs. For those starch-PVOH biopolymers with zero N and S
      contents home composting delivered the best environmental performance amongst
      biological treatment routes in most impact categories (except for GWP(100)). The
      landfill scenario performed generally well due largely to the 100-year time
      horizon and efficient energy recovery system modeled but this good performance is
      highly sensitive to assumptions adopted in landfill model.

PMID- 23131651
TI  - Development of a novel three-stage fermentation system converting food waste to
      hydrogen and methane.
AB  - In this study, a novel three-stage (lactate-+photo-H(2)+CH(4)) fermentation
      system was developed, which converts food waste to H(2) and CH(4), with an
      emphasis on achieving high H(2) yield. The system begins by first fermenting food
      waste to lactate, rather than acetate and butyrate, using indigenous lactic acid
      bacteria. Lactate fermentation effluent was then centrifuged, and the supernatant
      was used for H(2) production by photo-fermentation, while the residue was used
      for CH(4) production by anaerobic digestion. Overall, via the three-stage
      fermentation system, 41% and 37% of the energy content in the food waste was
      converted to H(2) and CH(4), respectively, corresponding to the electrical energy
      yield of 1146 MJ/ton-food waste, which is 1.4 times higher value than that of
      previous two-stage dark (H(2)+CH(4)) fermentation system. The H(2) yield based on
      hexose input was 8.35 mol H(2)/mol hexose(added), the highest value ever reported
      from actual organic waste.

PMID- 23131652
TI  - Solid state anaerobic co-digestion of yard waste and food waste for biogas
      production.
AB  - Food and yard wastes are available year round at low cost and have the potential
      to complement each other for SS-AD. The goal of this study was to determine
      optimal feedstock/effluent (F/E) and food waste/yard waste mixing ratios for
      optimal biogas production. Co-digestion of yard and food waste was carried out at
      F/E ratios of 1, 2, and 3. For each F/E ratio, food waste percentages of 0%, 10%,
      and 20%, based on dry volatile solids, were evaluated. Results showed increased
      methane yields and volumetric productivities as the percentage of food waste was
      increased to 10% and 20% of the substrate at F/E ratios of 2 and 1, respectively.
      This study showed that co-digestion of food waste with yard waste at specific
      ratios can improve digester operating characteristics and end performance metrics
      over SS-AD of yard waste alone.

PMID- 23131653
TI  - Catalytic conversion wood syngas to synthetic aviation turbine fuels over a
      multifunctional catalyst.
AB  - A continuous process involving gasification, syngas cleaning, and Fischer-Tropsch
      (FT) synthesis was developed to efficiently produce synthetic aviation turbine
      fuels (SATFs). Oak-tree wood chips were first gasified to syngas over a
      commercial pilot plant downdraft gasifier. The raw wood syngas contains about 47%
      N(2), 21% CO, 18% H(2), 12% CO(2,) 2% CH(4) and trace amounts of impurities. A
      purification reaction system was designed to remove the impurities in the syngas
      such as moisture, oxygen, sulfur, ammonia, and tar. The purified syngas meets the
      requirements for catalytic conversion to liquid fuels. A multi-functional
      catalyst was developed and tested for the catalytic conversion of wood syngas to
      SATFs. It was demonstrated that liquid fuels similar to commercial aviation
      turbine fuels (Jet A) was successfully synthesized from bio-syngas.

PMID- 23131654
TI  - Methane production from cattle manure supplemented with crude glycerin from the
      biodiesel industry in CSTR and IBR.
AB  - The aim of the present research work was to optimise biogas production from
      cattle manure by adding crude glycerin from the biodiesel industry. For this
      purpose, 6%v/v crude glycerin (the optimum amount according to previous research)
      was added to ground manure and the mixture was sonicated to enhance
      biodegradability prior to anaerobic co-digestion at 55  degrees C. Two different
      reactors were used: continuously stirred (CSTR) and induced bed (IBR). The
      methanol and pure glycerin contents of the crude glycerin used in this study were
      5.6% and 49.4% (w/w), respectively. The best results when operating in CSTR were
      obtained for an organic loading rate (OLR) of 5.4 kg COD/m(3) day, obtaining
      53.2m(3) biogas/t wet waste and 80.7% COD removal. When operating in IBR, the
      best results were obtained for an OLR of 6.44 kg COD/m(3)day, obtaining 89.6% COD
      removal and a biogas production of 56.5m(3)/t wet waste.

PMID- 23131655
TI  - Oxidative torrefaction of biomass residues and densification of torrefied sawdust
      to pellets.
AB  - Oxidative torrefaction of sawdust with a carrier gas containing 3-6% O(2) was
      investigated in a TG and a fluidized bed reactor, with the properties of the
      torrefied sawdust and pellets compared with traditional torrefaction without any
      O(2), as well as the dry raw material. It is found that the oxidative
      torrefaction process produced torrefied sawdust and pellets of similar properties
      as normally torrefied sawdust and corresponding pellets, especially on the
      density, energy consumption for pelletization, higher heating value and energy
      yield. For moisture absorption and hardness of the torrefied pellets, the
      oxidative torrefaction process showed slightly poor but negligible performance.
      Therefore, it is feasible to use oxygen laden combustion flue gases as the
      carrier gas for torrefaction of biomass. Besides, torrefied sawdust can be made
      into dense and strong pellets of high hydrophobicity at a higher die temperature
      than normally used in the production of traditional control pellets.

PMID- 23131656
TI  - Ensiling of fish industry waste for biogas production: a lab scale evaluation of
      biochemical methane potential (BMP) and kinetics.
AB  - Fish waste (FW) obtained from a fish processor was ensiled for biogas production.
      The FW silages were prepared by mixing FW with bread waste (BW) and brewery grain
      waste (BGW), and the quality of the prepared silages were evaluated. The biogas
      potentials of BW, BGW, three different types of FW, and FW silages were measured.
      A first-order kinetic model and the modified Gompertz model were also used to
      predict methane yield. The biogas and methane yield for FW silages after 96 days
      was calculated to be 671-763 mL/g VS and 441-482 mL/g VS, respectively. There
      were smaller differences between measured and predicted methane yield for FW
      silages when using a modified Gompertz model (1.1-4.3%) than when using a first
      order kinetic model (22.5-32.4%). The critical HRTs and technical digestion times
      (T(80-90)) for the FW silages were calculated to be 21.0-23.8 days and 40.5-52.8
      days, respectively.

PMID- 23131657
TI  - Biodegradation of chlorpyrifos and 3,5,6-trichloro-2-pyridinol by Cupriavidus sp.
      DT-1.
AB  - A bacterial strain, Cupriavidus sp. DT-1, capable of degrading chlorpyrifos and
      3,5,6-trichloro-2-pyridinol (TCP) and using these compounds as sole carbon source
      was isolated and characterized. Investigation of the degradation pathway showed
      that chlorpyrifos was first hydrolyzed to TCP, successively dechlorinated to 2
      pyridinol, and then subjected to the cleavage of the pyridine ring and further
      degradation. The mpd gene, encoding the enzyme responsible for chlorpyrifos
      hydrolysis to TCP, was cloned and expressed in Escherichia coli BL21. Inoculation
      of chlorpyrifos-contaminated soil with strain DT-1 resulted in a degradation rate
      of chlorpyrifos and TCP of 100% and 94.3%, respectively as compared to a rate of
      28.2% and 19.9% in uninoculated soil. This finding suggests that strain DT-1 has
      potential for use in bioremediation of chlorpyrifos-contaminated environments.

PMID- 23131658
TI  - Effect of different steam explosion conditions on methane potential and enzymatic
      saccharification of birch.
AB  - Birch (Betula pubescens) was steam exploded at 13 different conditions with
      temperatures ranging from 170 to 230  degrees C and residence times ranging from
      5 to 15 min. Increasing severity in the pretreatment led to degradation of xylan
      and formation of pseudo-lignin. The effect of the pretreatments was evaluated by
      running enzymatic saccharification and anaerobic digestion followed by analysis
      of sugar and methane yields, respectively. Enzymatically released glucose
      increased with pretreatment severity up to 220  degrees C for 10 min and levels
      of solubilized glucose reached 97% of the theoretical maximum. The highest
      methane yield (369 mL gVS(-1)) was obtained at a severity factor of 4.5 and this
      yield was 1.8 times higher than the yield from untreated birch. Enzymatic glucose
      yields and methane yields were generally correlated. The results indicate that
      steam-exploded birch can be effectively converted to either glucose or methane.

PMID- 23131659
TI  - Techno-economic analysis of monosaccharide production via fast pyrolysis of
      lignocellulose.
AB  - The economic feasibility of a facility producing monosaccharides, hydrogen and
      transportation fuels via fast pyrolysis and upgrading pathway was evaluated by
      modeling a 2000 dry metric ton biomass/day facility using Aspen Plus(r).
      Equipment sizing and cost were based on Aspen Economic Evaluation(r) software.
      The results indicate that monosaccharide production capacity could reach 338
      metric tons/day. Co-product yields of hydrogen and gasoline were 23.4 and 141
      metric tons/day, respectively. The total installed equipment and total capital
      costs were estimated to be $210 million and $326 million, respectively. A
      facility internal rate of return (IRR) of 11.4% based on market prices of
      $3.33/kg hydrogen, $2.92/gal gasoline and diesel, $0.64/kg monosaccharide was
      calculated. Sensitivity analysis demonstrates that fixed capital cost, feedstock
      cost, product yields, and product credits have the greatest impacts on facility
      IRR. Further research is needed to optimize yield of sugar via the proposed
      process to improve economic feasibility.

PMID- 23131660
TI  - Anti-inflammatory effect of conjugated linoleic acid in patients with Crohn's
      disease.

PMID- 23131661
TI  - Solitary peripheral pulmonary papilloma evaluation on frozen section: a potential
      pitfall for the pathologist.
AB  - Endobronchial papilloma is a rare entity that is in the differential for solitary
      pulmonary nodule. It almost always follows a benign course, with only rare
      malignant transformation being reported in the squamous variant. No malignant
      transformation of the glandular variant has been reported to the best of our
      knowledge, and therefore endobronchial papilloma must be distinguished from more
      aggressive neoplasms. This distinction is particularly important when one
      encounters this neoplasm in a peripheral location at frozen section. We report a
      case of a 65-year-old female with an incidentally discovered solitary peripheral
      pulmonary nodule identified during a commercial whole-body screening computed
      tomography (CT) scan. Interval scans revealed a concerning doubling time, and she
      presented to the surgical service for removal of the mass. Intraoperative frozen
      section evaluation revealed histologic characteristics favoring a benign
      neoplasm. Permanent histologic section revealed a glandular papilloma. Over 7
      years of follow-up revealed a benign clinical course.

PMID- 23131662
TI  - Characteristics of Social and Administrative Sciences graduate programs and
      strategies for student recruitment and future faculty development in the United
      States.
AB  - BACKGROUND: The rising demand of faculty in Social and Administrative Sciences
      (SAS) in pharmacy in the United States heightens the need to increase the number
      of Doctor of Philosophy (PhD) graduates in SAS who choose to pursue an academic
      career. OBJECTIVES: To describe the characteristics of SAS graduate programs and
      graduate students and identify strategies for student recruitment and future
      faculty development. METHODS: An Internet survey (phase I) with key informants
      (graduate program officers/department chairs) and semistructured telephone
      interviews (phase II) with phase I respondents were used. Items solicited data on
      recruitment strategies, number of students, stipends, support, and other relevant
      issues pertaining to graduate program administration. Descriptive statistics were
      tabulated. RESULTS: Of the 40 SAS graduate programs identified and contacted, 24
      completed the Internet survey (response rate [RR]=60.0%) and, of these, 16
      completed the telephone interview (RR=66.7%). At the time of the survey, the
      median number of graduate students with a U.S.-based PharmD degree was 3. An
      average annual stipend for graduate assistants was $20,825. The average time to
      PhD degree completion was 4.57 years, and approximately 31% of PhD graduates
      entered academia. Various strategies for recruitment and future faculty
      development were identified and documented. CONCLUSIONS: Findings allow SAS
      graduate programs to benchmark against other institutions with respect to their
      own achievement/strategies to remain competitive in student recruitment and
      development. Additional research is needed to determine the success of various
      recruitment strategies and identify potential new ones.

PMID- 23131663
TI  - A characterization of the current communication patterns in Danish community
      pharmacies - an observational study.
AB  - BACKGROUND: Community pharmacies have been trying to expand their core function
      by counseling customers at the counter. This has been challenging given that
      customers' interest in receiving counseling may be limited. OBJECTIVES: To
      characterize the current pharmacist-customer communication patterns to inform
      future studies and models of communication. METHODS: Non-participant structured
      observations based on the works of Stevenson et al. were conducted. A random
      selection of one hundred encounters in five pharmacies in Denmark was obtained.
      Type of encounter, type of medicine purchased and the age and gender of the
      customer were observed, and associations between the parameters identified.
      RESULTS: Customers initiated 13% of the dialogs, whereas 60% were initiated by
      the staff (with 38% of the customers declining the offer). 26% of the encounters
      saw no communication about the medicine. The customers' level of interest in
      counseling varied significantly and more with the type of medicine purchased than
      the level of encouragement from the staff to initiate a dialog. The customers'
      interest in dialog, in contrast with the staff behavior, depended significantly
      on age and gender. CONCLUSIONS: Customers' interest in counseling varies
      significantly. Pharmacy staff should take this into consideration when trying to
      optimize communication.

PMID- 23131664
TI  - Genomic occupancy of the transcriptional co-activators p300 and CBP.
AB  - The p300 and CBP co-activators are histone acetylases and central regulators of
      transcription in metazoans. The genomic occupancy of p300/CBP detected by ChIP
      seq experiments can be used to identify transcriptional enhancers. However,
      studies in Drosophila embryos suggest that there is a preference for some
      transcription factors in directing p300/CBP to the genome. Although p300/CBP
      occupancy in general correlates with gene activation, they can also be found at
      silent genomic regions, which does not result in histone acetylation. Polycomb
      mediated H3K27me3 is associated with repression, but does not preclude p300/CBP
      binding. An antagonism between H3K27ac and H3K27me3 indicates that p300/CBP may
      be involved in switching between repressed and active chromatin states.

PMID- 23131665
TI  - The role of epigenetic transcriptional regulation in BRCA1-mediated tumor
      suppression.
AB  - Mutation in BRCA1 accounts for half of all familial breast cancer cases. Recent
      studies have shown its role in the epigenetic regulation of an oncogenic
      microRNA, revealing a novel mode of tumor suppression that is independent of its
      well-established role in DNA repair and cell cycle regulation.

PMID- 23131666
TI  - Two faces of brd4: mitotic bookmark and transcriptional lynchpin.
AB  - The bromodomain protein BRD4 links cell cycle and transcription, bookmarking
      active genes during mitosis and serving as a scaffold for transcription factors.
      Our recent discovery that BRD4 is a RNA Polymerase II CTD kinase identifies a
      novel transcriptional function. Here we discuss our model in the context of
      current knowledge.

PMID- 23131667
TI  - The cell cycle rallies the transcription cycle: Cdc28/Cdk1 is a cell cycle
      regulated transcriptional CDK.
AB  - In the budding yeast Saccharomyces cerevisiae, the cyclin-dependent kinases
      (CDKs) Kin28, Bur1 and Ctk1 regulate basal transcription by phosphorylating the
      carboxyl-terminal domain (CTD) of RNA polymerase II. However, very little is
      known about the involvement of the cell cycle CDK Cdc28 in the transcription
      process. We have recently shown that, upon cell cycle entry, Cdc28 kinase
      activity boosts transcription of a subset of genes by directly stimulating the
      basal transcription machinery. Here, we discuss the biological significance of
      this finding and give our view of the kinase-dependent role of Cdc28 in
      regulation of RNA polymerase II.

PMID- 23131668
TI  - How to stop: the mysterious links among RNA polymerase II occupancy 3' of genes,
      mRNA 3' processing and termination.
AB  - Eukaryotic genes are transcribed by RNA polymerase II (RNAP II) through cycles of
      initiation, elongation and termination. Termination remains the least understood
      stage of transcription. Here we discuss the role of RNAP II occupancy downstream
      of the 3'ends of genes and its links with termination and mRNA 3' processing.

PMID- 23131669
TI  - Perilunate dislocation.

PMID- 23131670
TI  - Preparing young travellers for low resource destinations.

PMID- 23131671
TI  - Use of Mendelian randomisation to assess potential benefit of clinical
      intervention.

PMID- 23131672
TI  - Adding age and genetic risk to PSA test could improve screening for prostate
      cancer.

PMID- 23131673
TI  - Zoledronic acid prevents fractures in men with osteoporosis.

PMID- 23131674
TI  - Single application of ivermectin lotion helps get rid of head lice.

PMID- 23131675
TI  - Chemotherapy before surgery for colon cancer may improve survival, study shows.

PMID- 23131676
TI  - Indian authority withdraws patent for interferon granted to Roche.

PMID- 23131677
TI  - Private hospitals look to NHS for elective operations as private medical
      insurance falls.

PMID- 23131678
TI  - Dexamethasone topically accelerates peripheral nerve repair and target organ
      reinnervation: a transected sciatic nerve model in rat.
AB  - The objective was to assess the effect of topically administered dexamethasone on
      peripheral nerve regeneration and functional recovery. Sixty male healthy white
      Wistar rats were divided into four experimental groups (n = 15), randomly: in
      transected group (TC), left sciatic nerve was transected and stumps were fixed in
      the adjacent muscle. In treatment group defect was bridged using a silicone tube
      (SIL/Dexa) filled with 10 MUL dexamethasone (0.1 mg/kg). In silicone group (SIL),
      the tube was filled with phosphate-buffered saline alone. In sham-operated group
      (SHAM), sciatic nerve was exposed and manipulated. Each group was subdivided into
      three subgroups of five animals each and regenerated nerve fibres were studied 4,
      8 and 12 weeks after surgery. Functional study, gastrocnemius muscle mass and
      morphometric indices confirmed faster recovery of regenerated axons in SIL/Dexa
      than SIL group (p < 0.05). In immunohistochemistry, location of reactions to S
      100 in SIL/Dexa was clearly more positive than that in SIL group. When loaded in
      a silicone tube, dexamethasone improved functional recovery and morphometric
      indices of sciatic nerve. Topical application of this readily available agent
      offers the benefit of cost savings as well as avoiding the complications
      associated with systemic administration.

PMID- 23131679
TI  - Surgeon commitment to trauma care decreases missed injuries.
AB  - STUDY OBJECTIVE: Missed injuries sustain an important issue concerning patient
      safety and quality of care. The purpose of this study is to examine the effect of
      surgeon commitment to trauma care on missed injuries. We hypothesised that
      surgeons committed to the trauma service has less missed injuries than surgeons
      not committed to the trauma service would have. METHODS: By retrospective
      analysis of 976 adult patients admitted to the trauma intensive care unit (ICU)
      at an urban, university-based trauma centre. Missed injuries were compared
      between two groups; in group 1 the patients were evaluated and treated by the
      surgeons who were committed to the trauma service and in group 2 the patients
      were evaluated and treated by surgeons practicing mainly in other specialties.
      RESULTS: Patients had significantly lower rates of missed major or life
      threatening injuries when treated by group 1 surgeons. Logistic regression model
      revealed significant factors associated with missed major or life-threatening
      injuries including ISS and groups in which patients were treated by different
      group surgeons. CONCLUSIONS: Physicians will perform better when they are trained
      and interested in a specific area than those not trained, or even not having any
      particular interest in that specific area. Surgeons committed to the trauma
      service had less missed injuries in severely injured patients, and it is vital to
      improve patient safety and quality of care for trauma patients. Staff training
      and education for assessing severely injured patients and creating an open
      culture with detection and reduction of the potential for error are important and
      effective strategies in decreasing missed injuries and improving patient safety.

PMID- 23131681
TI  - Establishment of a robotic, high-throughput platform for the specific diagnosis
      of gastrointestinal nematode infections in sheep.
AB  - The accurate diagnosis of strongylid nematode infections is central to
      investigating their epidemiology and for parasite control. To overcome major
      limitations in sensitivity or specificity of traditional methods, including
      faecal egg count (FEC) and/or larval culture (LC), we evaluated and established a
      semi-automated, high throughput multiplexed-tandem PCR (MT-PCR) platform for the
      diagnosis of gastrointestinal strongylid nematode infections in sheep, and
      established its diagnostic sensitivity (100%) and specificity (87.5%) based on
      the testing of 100 faecal DNA samples from helminth-free sheep and 30 samples
      from sheep with infections confirmed by necropsy. Subsequently, the platform was
      employed to test 219 faecal samples from sheep with naturally acquired infections
      from various geographical localities within Australia and the results compared
      with those from conventional LC using 139 of the 219 samples. The results
      obtained using both MT-PCR and LC correlated significantly for most nematodes
      examined, but revealed that Oesophagostomum venulosum and Chabertia ovina
      (parasites of the large intestine) were significantly under-represented in the LC
      results. The results showed that Trichostrongylus spp. (87%), Teladorsagia
      circumcincta (80%) and Haemonchus contortus (67%) had the highest prevalences,
      followed by O. venulosum (51%) and C. ovina (12%). The molecular-diagnostic
      platform established can be used for species- or genus-specific diagnosis of
      patent nematode infections within 24h (compared with 7-10 days for LC), and is a
      sensitive and cost effective tool for routine application in research and service
      laboratories.

PMID- 23131680
TI  - Substantial genetic divergence between morphologically indistinguishable
      populations of Fasciola suggests the possibility of cryptic speciation.
AB  - The liver flukes, Fasciola hepatica and Fasciola gigantica, are considered to be
      sister species and between them present a major threat worldwide to livestock
      production. In this study sequence data have been employed from informative
      regions of the nuclear and mitochondrial genomes of over 200 morphologically F.
      hepatica-like or F. gigantica-like flukes from Europe, sub-Saharan Africa and
      South Asia to assess genetic diversity. Evidence is presented for the existence
      of four well-separated clades: African gigantica-like flukes, Indian gigantica
      like flukes, European hepatica-like flukes and African high-altitude hepatica
      like flukes. Application of the Biological Species Concept to trematodes is
      problematic; however, the degree of separation between these groups was
      sufficient for them to be considered as distinct species using the four times
      rule for speciation.

PMID- 23131684
TI  - Clipboard. Inspector General tells CMS to stop certifying new home health
      agencies in Texas and Florida.

PMID- 23131685
TI  - An orthodox perspective of the Jewish end-of-life experience.
AB  - This article provides insight into Jewish law, ethics, and cultural practices
      regarding pain management, care of the dying Jewish patient, and Jewish rituals
      after death across the care continuum. Clinically and culturally appropriate care
      provision is important in the setting of a hospital, nursing home, and community
      dwelling because of deep religious belief and practices, as well as life
      experiences such as the Holocaust. The recognition of deep spiritual and cultural
      practices from the interdisciplinary or interprofessional team serves to fulfill
      a holistic approach to the overall care of the patient and family.

PMID- 23131686
TI  - The advanced practice wound ostomy continence nurse in homecare.
AB  - Wound ostomy continence (WOC) programs are essential in any healthcare
      organization, including home care agencies, to provide comprehensive, high
      quality care. Advanced practice nurses (APNs) with assessment, diagnostic, and
      coordination skills are well suited to manage the complex patients being cared
      for by home care agencies. A number of research studies have assessed the
      credibility and value of APNs in the home care setting, caring for complex, frail
      patients. This article describes the role of the APN, and the role of the WOC
      specialist nurse, comparing similarities and differences. The advanced practice
      WOC nurse is now essential in the home care setting to manage the care of complex
      patients.

PMID- 23131688
TI  - The updated immunization recommendations for healthcare personnel.
AB  - Immunization recommendations for healthcare personnel were updated in a 2011
      report by the U.S. Advisory Committee on Immunization Practices. The
      recommendations apply to all paid and unpaid persons working in healthcare
      settings who might come into contact with patients or infectious materials. The
      recommendations apply to all healthcare settings including persons who provide
      home healthcare and hospice.

PMID- 23131690
TI  - Chronic obstructive pulmonary disease and asthma.
AB  - Obstructive lung disorders are responsible for functional limitations and the
      deaths of millions of Americans. Chronic obstructive pulmonary disease (COPD) is
      in the top 5 leading causes of death and the incidence is climbing. Home
      healthcare and hospice nurses should be aware of current management strategies,
      including nonpharmacologic therapies. A case-study format is used to introduce
      the subject, a brief review of pathophysiology of COPD and asthma is discussed,
      and evidence-based treatment strategies are reviewed, including nursing
      management to improve patient function.

PMID- 23131692
TI  - Evidence-based practices in home care: how are we doing?

PMID- 23131693
TI  - Honored communications: the emergence of hidden stories toward the end of life.

PMID- 23131695
TI  - Analytical toxicology of emerging drugs of abuse--an update.
AB  - The steady increase of new drugs of abuse on the illicit drug market is a great
      challenge for analytical toxicologists. Because most of these new drugs or drug
      classes are not included in established analytical methods targeting classic
      drugs of abuse, analytical procedures must be adapted or new procedures must be
      developed to cover such new compounds. This review summarizes procedures for
      analysis of these drugs of abuse published from January 2009 to January 2012
      covering the following classes of emerging drugs of abuse as follows: beta-keto
      amphetamines, pyrrolidinophenones, tryptamines, and synthetic cannabinoids.

PMID- 23131696
TI  - Chronopharmacokinetics of mycophenolic acid and its glucuronide and acyl
      glucuronide metabolites in kidney transplant recipients converted from
      cyclosporine to everolimus.
AB  - BACKGROUND: The influence of the conversion from cyclosporine (CsA) to everolimus
      (EVR) on the chronopharmacokinetics of mycophenolic acid (MPA) and its
      glucuronide (MPAG) and acyl glucuronide (acyl-MPAG) metabolites in patients
      receiving enteric-coated mycophenolate sodium (EC-MPS) has not been studied.
      METHODS: We evaluated daytime and nighttime steady-state MPA, MPAG, and acyl-MPAG
      pharmacokinetics in 24 stable kidney transplant recipients while receiving
      cyclosporine and 28 days after conversion from CsA to EVR. The effect of
      concomitant treatment and the circadian difference on AUC(t,ss) and C(max,ss)
      were assessed using a linear mixed model. RESULTS: After conversion from CsA to
      EVR, MPA AUC(t,ss) was 43% higher (29% daytime and 58% during nighttime), whereas
      MPAG AUC(t,ss) was 33% lower (35% daytime and 30% during nighttime) and acyl-MPAG
      AUC(t,ss) was 31% lower (36% during daytime and 26% nighttime). Compared with
      daytime, MPA AUC(t,ss) was 25% lower (32% with CsA and 17% with EVR), MPAG
      AUC(t,ss) was 24% lower (26% with CsA and 21% with EVR), and acyl-MPAG AUC(t,ss)
      was 26% lower (32% with CsA and 21% with EVR) during nighttime. After conversion
      from CsA to EVR, MPAG:MPA and acyl-MPAG:MPA AUC(t,ss) ratios were 50% lower but
      were not different during daytime compared with nighttime EC-MPS administration.
      There was no correlation between CsA or EVR concentrations with MPA, MPAG, and
      acyl-MPAG exposures during daytime and nighttime. At least 1 adverse event was
      reported in 70.8% of patients receiving EC-MPS and CsA and in 91.7% receiving EC
      MPS and EVR. CONCLUSION: In stable kidney transplant recipients receiving EC-MPS
      and steroids, exposures to MPA, MPAG, and acyl-MPAG were lower during nighttime
      compared with daytime, both with CsA or EVR. This circadian effect on MPA
      exposure did not correlate with CsA or EVR concentrations or with altered MPAG
      and acyl-MPAG formation.

PMID- 23131697
TI  - UGT1A9, UGT2B7, and MRP2 genotypes can predict mycophenolic acid pharmacokinetic
      variability in pediatric kidney transplant recipients.
AB  - BACKGROUND: Mycophenolic acid (MPA) exposure in pediatric patients with kidney
      transplant receiving body surface area (BSA)-based dosing exhibits large
      variability. Several genetic variants in glucuronosyltransferases (UGTs) and of
      multidrug resistance-associated protein 2 (MRP2) have independently been
      suggested to predict MPA exposure in adult patients with varying results. Here,
      the combined contribution of these genetic variants to MPA pharmacokinetic
      variability was investigated in pediatric renal transplant recipients who were on
      mycophenolic mofetil maintenance therapy. METHODS: MPA and MPA-glucuronide
      concentrations from 32 patients were quantified by high-performance liquid
      chromatography. MPA exposure (AUC) was estimated using a 4-point abbreviated
      sampling strategy (predose/trough and 20 minutes, 1 hour, and 3 hours after dose)
      using a validated pediatric Bayesian estimator. Genotyping was performed for all
      of the following single nucleotide polymorphisms (SNPs): UGT1A8 830G>A(*3),
      UGT1A9 98T>C(*3), UGT1A9-440C>T, UGT1A9-2152C>T, UGT1A9-275T>A, UGT2B7-900A>G,
      and MRP2-24T>C. RESULTS: Recipients heterozygous for MRP2-24T>C who also had
      UGT1A9-440C>T or UGT2B7-900A>G (n = 4), and MRP2-24T>C-negative recipients having
      both UGT1A9-440C>T and UGT2B7-900A>G (n = 5) showed a 2.2 and 1.7 times higher
      dose-dependent and BSA-normalized MPA-AUC compared with carriers of no or only 1
      UGT-SNP (P < 0.001 and P = 0.01, respectively) (n = 7). Dose-dependent and BSA
      normalized predose MPA concentrations were 3.0 and 2.4 times higher, respectively
      (P < 0.001). Interindividual variability in peak concentrations could be
      explained by the presence of the UGT1A9-440C>T genotype (P < 0.05). CONCLUSION:
      Our preliminary study demonstrates that combined UGT1A9-440C>T, UGT2B7-900A>G,
      and MRP2-24T>C polymorphisms can be important predictors of interindividual
      variability in MPA exposure in the pediatric population.

PMID- 23131698
TI  - Population pharmacokinetics of everolimus in cardiac recipients: comedications,
      ABCB1, and CYP3A5 polymorphisms.
AB  - BACKGROUND: The aim of this study was, using routine drug monitoring data, to
      identify patient characteristics that may influence everolimus (EVE)
      pharmacokinetic parameters and to develop a population pharmacokinetic model to
      predict EVE whole blood concentrations in cardiac recipients. METHODS: Fifty-nine
      patients were enrolled in the prospective study. Patient's characteristics were
      recorded including biological covariates and treatments. CYP3A5 and ABCB1
      polymorphisms were determined. Seven hundred seventy-five EVE blood samples were
      collected for routine drug monitoring. Population pharmacokinetic modeling was
      carried out using the nonlinear mixed-effects modeling program. Results were
      analyzed according to a 1-compartment pharmacokinetic model with linear
      absorption and elimination. The model was evaluated using a bootstrap method and
      a visual predictive check procedure. RESULTS: The pharmacokinetic of EVE in
      cardiac recipients was best described by a 1-compartment model. Interindividual
      variability was best described by an exponential error model and residual error
      by a proportional plus additive error model. Estimation of EVE apparent clearance
      (3.33 +/- 0.20 L/h) and apparent volume of distribution (146 +/- 33 L) were in
      accordance with previously published data. Bilirubinemia and cyclosporine
      significantly influenced EVE clearance. Some covariates that were expected to
      influence EVE clearance, for example, ABCB1 and CYP3A5 polymorphisms, were not
      evidenced. No covariates influenced the volume of distribution of EVE.
      CONCLUSIONS: This study is the first population pharmacokinetic model of EVE in
      heart transplantation patients. It allows a better description of the
      pharmacokinetics of EVE. The present population pharmacokinetic model allows
      estimating a priori and a posteriori EVE concentrations in cardiac recipients and
      could limit the over and under drug exposure in this population.

PMID- 23131699
TI  - Respect in the care of older patients in acute hospitals.
AB  - The aim of this study was to describe the experiences of older patients and their
      next of kin with regards to respect in the care given in an acute hospital. The
      data were collected using tape-recorded interviews (10 patients and 10 next of
      kin) and analysed via inductive content analysis. Based on the analysis, the
      concept of respect can be defined by the actions taken by nurses (polite
      behaviour, the patience to listen, reassurance, response to information needs,
      assistance in basic needs, provision of pain relief, response to wishes and time
      management) and next of kin (support, assistance and advocacy) and by factors
      related to the environment (appreciation of older people in society, management
      of health-care organizations, the nursing culture, the flow of information and
      patient placement). The information will be used to develop an instrument for
      assessing how well respect is maintained in the care of older patients.

PMID- 23131700
TI  - Dignity in care in the clinical setting: a narrative review.
AB  - This review aimed to explore nursing literature and research on dignity in care
      of inpatients and to evaluate how the care patients received in the hospital
      setting was related to perceived feelings of being dignified or undignified.
      Studies conducted between 2000 and 2010 were considered, using Cumulative Index
      to Nursing and Allied Health Literature and MEDLINE, and the search terms
      'patient dignity', 'dignity in care', 'human dignity and nursing' and 'dignity
      and nursing ethics'. Findings revealed, from the perspectives of nurses and
      patients, that dignity in care in the hospital setting is seen to be influenced
      by physical environment, staff attitude and behaviour, organisational culture and
      patient independence. This review can help nurses to better understand dignity in
      care, and for policy makers, there are implications about determining the
      physical environment, staff attitude and behaviour and organisational culture
      needed to promote patient dignity in nursing. By identifying the most important
      factors from patients' and nurses' perspectives that contribute to dignity in
      care, nursing interventions, such as campaigns and education in clinical
      practice, can be developed.

PMID- 23131701
TI  - Ethical decision-making and professional behaviour among nurses: a correlational
      study.
AB  - This study examined the relationship between nurses' ethical decision-making
      levels and their professional behaviours. Data were collected from 225 nurses who
      were recruited from university hospitals in Ankara using proportionate sampling.
      Data were analysed using descriptive statistics and Pearson correlations. Most of
      the nurses were familiar with ethical dilemmas in nursing practice. The Nursing
      Principled Thinking level was above average, while the Practical Consideration
      level was average. Nurses' professionalism level was low. There was a positive
      but weak correlation between professional behaviours of the nurses and their
      ethical decision-making levels. Increasing nurses' professionalism level can
      provide a positive contribution to the ethical decision-making level.

PMID- 23131702
TI  - Partial colpectomy is a risk factor for urologic complications of colorectal
      resection for endometriosis.
AB  - STUDY OBJECTIVE: To evaluate urologic complications after colorectal resection
      for endometriosis. DESIGN: Cohort study (Canadian Task Force classification II
      2). SETTING: Tertiary referral university hospital and expert center in
      endometriosis. PATIENTS: One hundred sixty-six women with colorectal
      endometriosis proven by transvaginal sonography and magnetic resonance imaging.
      INTERVENTION: Open or laparoscopic colorectal resection for endometriosis.
      MEASUREMENTS AND MAIN RESULTS: Forty-four patients (26.5%) experienced at least 1
      urologic complication, including infection. Eight patients (4.8%) experienced
      postoperative symptomatic hydronephrosis requiring ureteral stent in 3 cases, a
      percutaneous nephrostomy in 1 case, and expectant management for the last 4.
      Urologic fistulas occurred in 5 patients (3%). Postoperative voiding dysfunction
      requiring self-catheterization was observed in 48 patients (28.9%). With
      univariate analysis, a relationship was found between voiding dysfunction and
      partial colpectomy (p = .001) and American Society of Reproductive Medicine total
      score (p = .02), and between the occurrence of urinary fistula and the use of
      prophylactic ureteral catheterization (p = .015) and parametrectomy (p = .02). A
      relationship was found between postoperative symptomatic hydronephrosis and the
      use of prophylactic ureteral catheterization (p = .003). CONCLUSION: Colorectal
      resection for endometriosis can lead to urologic complications, particularly for
      patients requiring partial colpectomy, of which patients need to be informed.

PMID- 23131703
TI  - Does this dementia patient meet the prognosis eligibility requirements for
      hospice enrollment?

PMID- 23131704
TI  - Antidepressant drugs.
AB  - Therapeutic Reviews aim to provide essential independent information for health
      professionals about drugs used in palliative and hospice care. Additional content
      is available on www.palliativedrugs.com. Country-specific books (Hospice and
      Palliative Care Formulary USA, and Palliative Care Formulary, British and
      Canadian editions) are also available and can be ordered from
      www.palliativedrugs.com. The series editors welcome feedback on the articles
      (hq@palliativedrugs.com).

PMID- 23131706
TI  - Prospective evaluation of the frequency and treatment of restless legs syndrome
      in a palliative care unit.

PMID- 23131707
TI  - Clinical implication of protease-activated receptor-2 in idiopathic pulmonary
      fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a lethal pulmonary disease which is
      characterized by progressive fibrosis. In general, the exaggerated activation of
      the coagulation cascade has been observed during initiation or maintenance of the
      fibrotic disease. In a recent study, protease-activated receptor (PAR)-2, which
      plays a key role in coagulation cascade, was up-regulated in IPF patients,
      however, its clinical implications have not been understood. The objective of the
      present study was to evaluate the clinical significance of PAR-2 expression in
      the alveolar epithelial cells of IPF patients. PAR-2 expression was evaluated by
      immunohistochemical method in formalin-fixed and paraffin-embedded tissues of
      surgical lung biopsies from patients with IPF. Fibrosis scores from hematoxylin
      and eosin-stained lung sections and honeycombing scores in chest CT were
      calculated. Medical records were retrospectively reviewed and the correlation
      between the expression of PAR-2 and clinical profiles were assessed. Among thirty
      three IPF patients, PAR-2 expression was observed in 25 (75.8%). The lymphocyte
      counts in peripheral blood (2317 vs. 1753, p = 0.044) and honeycombing scores in
      chest CT (4.0 vs. 3.0 p = 0.046) were higher in PAR-2 positive group compared
      with PAR-2 negative group. During a follow-up duration of median 40.3 months, 7
      (21.2%) patients died and they were all included in the PAR-2 positive group (p =
      0.113). We conclude that PAR-2 is expressed in the alveolar epithelial cells of a
      substantial number of IPF patients, and the expression of PAR-2 significantly
      correlates with the extent of honeycombing shown in chest CT.

PMID- 23131708
TI  - Electronic structures and optical properties of the IPR-violating C60X8 (X = H,
      F, and Cl) fullerene compounds: a computational study.
AB  - Stimulated by the preparation and characterization of the isolated pentagon rule
      (IPR) violating chlorofullerene: C(60)Cl(8) (Nat. Mater. 2008, 7, 790-794), we
      have performed a systematic investigation on the structural stabilities,
      electronic and optical properties of the IPR-violating C(60)X(8) (X = H, F, and
      Cl) fullerene compounds via density functional theory. The large energy gaps
      between the highest occupied and the lowest unoccupied molecular orbitals provide
      a clear indication of high chemical stabilities of C(60)X(8) derivatives, and
      moreover, the C(60)X(8) molecules present great aromatic character with the
      negative nucleus independent chemical shift values. In the addition reactions of
      C(60) (C(2v)) + 4X(2) -> C(60)X(8), a series of exothermic processes are
      involved, with high reaction energies ranging from -71.97 to -233.16 kcal mol(
      1). An investigation on the electronic property shows that C(60)F(8) and
      C(60)Cl(8) could be excellent electron acceptors as a consequence of large
      vertical electron affinities. The density of state analysis suggests that the
      frontier molecular orbitals of C(60)X(8) are mainly from the carbon orbitals of
      two separate annulene subunits, and the influence from X atoms is secondary. In
      addition, the ultraviolet-visible spectra and second-order hyperpolarizabilities
      of C(60)X(8) are calculated by means of time-dependent density functional theory
      and a finite field approach, respectively. Both the average static linear
      polarizability <alpha> and second-order hyperpolarizability <gamma> of C(60)X(8)
      increase greatly compared to those of C(60).

PMID- 23131709
TI  - Stimulation of the motor cortex and corticospinal tract to assess human muscle
      fatigue.
AB  - This review aims to characterize fatigue-related changes in corticospinal
      excitability and inhibition in healthy subjects. Transcranial magnetic
      stimulation (TMS) has been extensively used in recent years to investigate
      modifications within the brain during and after fatiguing exercise. Single-pulse
      TMS reveals reduction in motor-evoked potentials (MEP) when measured in relaxed
      muscle following sustained fatiguing contractions. This modulation of
      corticospinal excitability observed in relaxed muscle is probably not specific to
      the fatigue induced by the motor task. During maximal and submaximal fatiguing
      contractions, voluntary activation measured by TMS decreases, suggesting the
      presence of supraspinal fatigue. The demonstration of supraspinal fatigue does
      not eliminate the possibility of spinal contribution to central fatigue.
      Concomitant measurement of TMS-induced MEP and cervicomedullary MEP in the
      contracting muscle, appropriately normalized to maximal muscle compound action
      potential, is necessary to determine the relative contribution of cortical and
      spinal mechanisms in the development of central fatigue. Recent studies comparing
      electromyographic (EMG) responses to paired-pulse stimuli at the cortical and
      subcortical levels suggest that impaired motoneuron responsiveness rather than
      intracortical inhibition may contribute to the development of central fatigue.
      This review examines the mechanical and EMG responses elicited by TMS (single-
      and paired-pulse) and cervicomedullary stimulation both during and after a
      fatiguing exercise. Particular attention is given to the muscle state and the
      type of fatiguing exercise when assessing and interpreting fatigue-induced
      changes in these parameters. Methodological concerns and future research
      interests are also considered.

PMID- 23131710
TI  - Corticotropin-releasing hormone system polymorphisms are associated with
      children's cortisol reactivity.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis underlies both adaptive and
      maladaptive responses to stress and may be an important marker of childhood
      vulnerability to psychopathology, although little is known about genetic variants
      that influence cortisol reactivity. We therefore examined associations between
      corticotrophin-releasing hormone (CRH) system gene (CRH, CRHR1 and CRHBP)
      variants and cortisol reactivity in preschoolers. A community sample of 409 three
      year-old children completed a standardized stress task to elicit HPA axis
      activation. Salivary samples were obtained at the baseline and at 10-min
      intervals post-stress for a total of six samples. Salivary cortisol was measured
      using standard ELISA (enzyme-linked immunosorbent assay) protocols and cortisol
      reactivity was operationalized by calculating cortisol change scores ([baseline]
      [peak cortisol post-stressor]). A single nucleotide polymorphism (SNP) marker
      panel containing 18 SNPs was used to tag the full-length CRH (4 SNPs), CRHR1 (7
      SNPs) and CRHBP (7 SNPs) genes. Significant main effects on children's cortisol
      reactivity (all ps<0.05) were found for loci on CRHR1 and CRHBP. Haplotypes of
      the CRHR1 linkage region were also associated with cortisol reactivity (all
      ps<0.01). Additionally, we found multiple interactions between tag-SNPs in all
      three gene-coding regions predicting cortisol reactivity (all ps<0.05).
      Individual differences in children's cortisol reactivity are related to genetic
      variation in CRH system gene-coding regions. Our results have important
      implications for future research on the role of HPA axis function in the
      development of disorders such as anxiety and depression.

PMID- 23131711
TI  - Participation of endocannabinoids in rapid suppression of stress responses by
      glucocorticoids in neonates.
AB  - In adult rodents, endocannabinoids (eCBs) regulate fast glucocorticoid (GC)
      feedback in the hypothalamus-pituitary adrenal (HPA) axis, acting as retrograde
      messengers that bind to cannabinoid receptors (CB1R) and inhibit glutamate
      release from presynaptic CRH neurons in the paraventricular nucleus of the
      hypothalamus (PVN). During the first two weeks of life, rat pups exhibit
      significant CRH and ACTH responses to stress although the adrenal GC output
      remains reduced. At the same time, pups also display increased sensitivity to GC
      feedback, but it is unclear whether eCBs play a role in mediating fast GC
      feedback in neonatal life. In our studies, we examined the role of eCBs in the
      rapid suppression of anoxia-induced ACTH release and determined whether eCB
      action could be modulated by the levels of circulating GCs present at the time of
      stress. PND8 pups were subjected to 3-min anoxia with AM251, a CB1R blocker,
      injected 30 min prior to stress onset. The effects of either metyrapone (MET) (a
      steroidogenic 11 beta-hydroxylase blocker) or methylprednisolone (PRED) (a
      synthetic GC) pretreatment on AM251 effect and the stress response were
      evaluated. Treatment with AM251 before stress onset tended to increase overall
      ACTH and CORT secretion, and also delayed the return to baseline ACTH. The AM251
      effect on ACTH in PND8 pups was lost in MET-treated pups, who exhibited high
      basal and stimulated ACTH release and no CORT response to stress.
      Methylprednisolone suppressed ACTH stress responses although AM251 still delayed
      restoration of ACTH levels to the baseline. This suggests that the eCB effect on
      ACTH secretion in neonates is most evident when there is a dynamic fluctuation of
      corticosterone levels. Interestingly, AM251 increased basal and stimulated
      corticosterone secretion in all treatments including MET, suggestive of a direct
      action of CB1R blockade on adrenal steroidogenesis.

PMID- 23131712
TI  - Expression of nicotinic acetylcholine receptor subunit mRNA in mouse bladder
      afferent neurons.
AB  - Nicotinic acetylcholine receptors (nAChR) influence bladder afferent activity and
      reflex sensitivity, and have been suggested as potential targets for treating
      detrusor overactivity. Mechanisms may include indirect effects, e.g. involving
      the urothelium, and direct action on nAChR expressed by afferent neurons. Here we
      determined the nAChR repertoire of bladder afferent neurons by retrograde
      neuronal tracing and laser-assisted microdissection/reverse transcriptase
      polymerase chain reaction (RT-PCR), and quantified retrogradely labelled
      nAChRalpha3-subunit-expressing neurons by immunohistochemistry in nAChR
      alpha3beta4alpha5 cluster enhanced green fluorescent protein (eGFP) reporter
      mice. Bladder afferents distinctly expressed mRNAs encoding for nAChR-subunits
      alpha3, alpha6, alpha7, beta2-4, and weakly alpha4. Based upon known
      combinatorial patterns of subunits, this predicts the expression of at least
      three basically different subunits of nAChR - alpha3(*), alpha6(*) and alpha7(*) 
      and of additional combinations with beta-subunits and alpha5. Bladder afferents
      were of all sizes, and their majority (69%; n=1367) were eGFP-nAChRalpha3
      positive. Immunofluorescence revealed immunoreactivities to neurofilament 68
      (NF68), transient receptor potential cation channel vanilloid 1 (TRPV1),
      substance P (SP) and calcitonin gene-related peptide (CGRP) in eGFP-nAChRalpha3
      positive and -negative neurons. For each antigen, all possible combinations of
      colocalisation with eGFP-nAChRalpha3 were observed, with eGFP-nAChRalpha3
      positive bladder neurons without additional immunoreactivity being most numerous,
      followed by triple-labelled neurons. In conclusion, more than one population of
      bladder afferent neurons expresses nAChR, indicating that peripheral nicotinic
      initiation and modulation of bladder reflexes might result, in addition to
      indirect effects, from the direct activation of sensory terminals. The expression
      of multiple nAChR subunits offers the potential of selectively addressing
      functional aspects and/or sensory neuron subpopulations.

PMID- 23131713
TI  - Two decades of exposure assessment studies on chromate production waste in Jersey
      City, New Jersey--what we have learned about exposure characterization and its
      value to public health and remediation.
AB  - During much of the twentieth century, Jersey City, New Jersey was the leading
      center of chromate production in the United States. Chromate production produced
      huge volumes of chromium ore-processing residue containing many parts per million
      of hexavalent chromium. Starting in the 1990s, we undertook a series of studies
      to identify exposed populations, sources and pathways of exposure and the
      effectiveness of remediation activities in Jersey City. These studies revealed
      the effectiveness and success of the remediation activities. The sequence of
      studies presented here, builds on the lessons learned from each preceding study
      and illustrates how these studies advanced the field of exposure science in
      important ways, including the use of household dust as a measure of exposure to
      contaminants originating in the outdoor environment; development of effective and
      reproducible dust sampling; use of household dust to track temporal changes in
      exposure; understanding of the spatial relationship between sources of passive
      outdoor particulate emissions and residential exposure; use of focused
      biomonitoring to assess exposure under conditions of large inter-individual
      variability; and utility of linking environmental monitoring and biomonitoring.
      For chromium, the studies have demonstrated the use of Cr(+6)-specific analytical
      methods for measuring low concentrations of Cr(+6) in household dust and
      understanding of the occurrence of Cr(+6) in the background residential
      environment. We strongly recommend that environmental and public health agencies
      evaluate sites for their potential for off-site exposure and apply these tools in
      cases with significant potential as appropriate. This approach is especially
      important when contamination is widespread and/or a large population is
      potentially exposed. In such cases, these tools should be used to identify,
      characterize and then reduce the exposure to the off-site as well as on-site
      population. Importantly, these tools can be used in a demonstrable and
      quantifiable manner to provide both clarity and closure to concerned
      stakeholders.

PMID- 23131714
TI  - Characterization of radiofrequency field emissions from smart meters.
AB  - This study presents measurement data that describe radiofrequency emission levels
      and patterns from smart meters (rated nominally at 1 W) currently deployed in
      Pacific Gas and Electric Company's service territory in northern California. The
      smart meters in our investigation could not be set to operate continuously and
      required a Field Service Unit to induce short periods of emitted fields. To
      obtain peak field data under both laboratory and ambient conditions, a spectrum
      analyzer scanned across the 83 transmitting channels between 902 and 928 MHz used
      by the smart meter on a random frequency-hopping basis. To obtain data describing
      temporal emission patterns, the analyzer operated in scope mode. Duty cycle was
      estimated using transmit data acquired by the system operator from over 88,000 m.
      Instantaneous peak fields at 0.3 m in front of the meters were no more than 15%
      of the US Federal Communications Commission (FCC) exposure limit for the general
      public, and 99.9% of the meters operated with a duty cycle of 1.12% or less
      during the sampling period. In a sample of measurements in six single-detached
      residences equipped with individual smart meters, no interior measurement of peak
      field exceeded 1% of the FCC's general public exposure limit.

PMID- 23131715
TI  - Investigations of a thermosensitive gel to temporarily occlude crural arteries in
      femoro-distal bypass surgery.
AB  - OBJECTIVES: Long occlusions in calcified crural arteries are a major cause of
      endovascular technical failure in patients with critical limb ischaemia.
      Therefore, distal bypasses are mainly performed in patients with heavily
      calcified arteries and with consequently delicate clamping. A new reverse
      thermosensitive polymer (RTP) is an alternative option to occlude target vessels.
      The aim of the study is to report our technical experience with RTP and to assess
      its safety and efficiency to temporarily occlude small calcified arteries during
      anastomosis time. METHODS: Between July 2010 and December 2011, we used RTP to
      occlude crural arteries in 20 consecutive patients with 20 venous distal
      bypasses. We recorded several operative parameters, such as volume of injected
      RTP, duration of occlusion and anastomotic time. Quality of occlusion was
      subjectively evaluated. Routine on-table angiography was performed to search for
      plug emboli. Primary patency, limb salvage and survival rates were reported at 6
      months. RESULTS: In all patients, crural artery occlusion was achieved with the
      RTP without the use of an adjunct occlusion device. Mean volume of RTP used was
      0.3 ml proximally and 0.25 ml distally. Mean duration of occlusion was 14.4 +/-
      4.5 min, while completion of the distal anastomosis lasted 13.4 +/- 4.3 min.
      Quality of occlusion was judged as excellent in eight cases and good in 12 cases.
      Residual plugs were observed in two patients and removed with an embolectomy
      catheter, before we amended the technique for dissolution of RTP. At 6 months,
      primary patency rate was 75% but limb salvage rate was 87.5%. The 30-day
      mortality rate was 10%. CONCLUSIONS: This study shows that RTP is safe when
      properly dissolved and effective to occlude small calcified arteries for
      completion of distal anastomosis.

PMID- 23131716
TI  - [Particular maternal or fetal clinical conditions influencing the choice of the
      mode of delivery in case of previous cesarean].
AB  - OBJECTIVE: To determine how particular maternal (age>35 years, multiparity,
      diabetes and obesity) or fetal (breech presentation, twin pregnancy, macrosomia,
      prolonged pregnancy, preterm delivery) clinical conditions, potentially
      associated with increased risk of failed trial of labor, uterine rupture, and
      perinatal asphyxia, should indicate a planned cesarean delivery or could still
      allow a planned vaginal birth after cesarean. METHODS: The PubMed database, the
      Cochrane Library and the recommendations from the French and foreign obstetrical
      societies or colleges have been consulted. RESULTS: For grand multiparous
      patients or preterm birth, a planned vaginal delivery should be encouraged
      (gradeC). For patients with a fetus estimated more than 4500 g, especially in the
      absence of previous vaginal delivery, or in case of supermorbid obesity (BMI>50),
      a planned cesarean delivery is recommended (gradeC). For all other clinical
      conditions (maternal age>35 years, diabetes, morbid obesity, breech presentation,
      twin pregnancy, prolonged pregnancy), although planned vaginal delivery is
      possible, a planned mode of delivery cannot be recommended because the levels of
      evidences are too low in case of previous cesarean (gradeC). CONCLUSIONS: Only
      few particular clinical conditions justify, by themselves, a planned cesarean
      delivery (EL3).

PMID- 23131717
TI  - Super-dose anti-VEGF (SAVE) trial: 2.0 mg intravitreal ranibizumab for
      recalcitrant neovascular macular degeneration-primary end point.
AB  - PURPOSE: To determine whether a higher dose of intravitreal ranibizumab could
      improve the anatomy and best-corrected visual acuity (BCVA) in eyes with
      neovascular age-related macular degeneration (AMD) with persistent disease
      activity despite monthly intravitreal anti-vascular endothelial growth factor
      (VEGF) injections. DESIGN: Phase I to II multicenter, open-label, controlled
      clinical trial. PARTICIPANTS: Eighty-seven patients with recalcitrant neovascular
      AMD, defined as having leakage on fundus fluorescein angiography or spectral
      domain optical coherence tomography (SD-OCT) despite monthly anti-VEGF
      injections. METHODS: Patients were treated with 2.0-mg ranibizumab injections
      monthly for 3 doses and monitored with Early Treatment Diabetic Retinopathy Study
      (ETDRS) 4-m refractions, clinical examinations, and SD-OCT. MAIN OUTCOME
      MEASURES: The mean change in baseline visual acuity (VA), the percentage of
      patients who experienced a loss or gain of 15 or more letters in ETDRS BCVA, the
      mean change in central retinal thickness, and the incidence of adverse events.
      RESULTS: Eighty-seven patients with an average of 24 injections before enrollment
      and a mean of 10.4 injections in the preceding 12 months had a mean refracted VA
      of 69.2 ETDRS letters (20/41 Snellen) and a mean central subfield of 422 MUm at
      baseline. Mean VA gain over baseline was +2.5 letters at day 7 (n = 82), +3.7
      letters at month 1 (n = 87), +3.9 letters at month 2 (n = 87), and +3.3 letters
      at month 3 (20/36 Snellen; P = 0.001; n = 86). Anatomic outcomes showed a mean
      optical coherence tomography central subfield thickness improvement from baseline
      of -48.4 MUm at day 7 (n = 84), -37.5 MUm at month 1 (n = 87), -42.4 MUm at month
      2 (n = 85), and -33.1 MUm at month 3 (P = 0.01; n = 86). CONCLUSIONS:
      Intravitreal injections of 2.0 mg ranibizumab led to statistically significant VA
      gains and anatomic improvement in patients with persistent intraretinal,
      subretinal, or subretinal pigment epithelial fluid during a previous regimen of
      chronic monthly 0.5-mg ranibizumab injections.

PMID- 23131718
TI  - Genetic association of refractive error and axial length with 15q14 but not 15q25
      in the Blue Mountains Eye Study cohort.
AB  - PURPOSE: Myopia is a common complex condition influenced by genetic and
      environmental factors. Two recent genome-wide association studies have identified
      loci on chromosomes 15q25 and 15q14 associated with refractive error in Caucasian
      populations. Our study aimed to assess the association of these 2 loci with
      refractive error and ocular biometric measures in an independent ethnically
      matched Caucasian cohort. DESIGN: Genetic association study using unrelated
      individuals. PARTICIPANTS: Blue Mountains Eye Study (BMES) cohort. A total of
      1571 individuals were included in this study. METHODS: Single nucleotide
      polymorphism (SNP) genotype data were collected from the BMES cohort as part of
      the Wellcome Trust Case Control Consortium 2. Imputation was performed using MACH
      version 1.1.16, and statistical analysis was conducted using PLINK. Association
      tests were performed at both loci using refractive error (spherical equivalent),
      axial length, corneal curvature, and anterior chamber depth as the phenotypes.
      MAIN OUTCOME MEASURES: Refractive error, axial length, corneal curvature, and
      anterior chamber depth. RESULTS: A total of 1571 individuals were available from
      the BMES for analysis. A statistically significant association for refractive
      error was evident for SNPs at the 15q14 locus, with P values ranging from 1.5 *
      10(-2) at rs685352 to 6.4 * 10(-4) at rs560764, whereas association could not be
      confirmed for SNPs at the 15q25 locus, with P values ranging from 8.0 * 10(-1) to
      6.4 * 10(-1). Ocular biometric analysis revealed that axial length was the most
      likely trait underlying the refractive error association at the 15q14 locus for
      SNPs rs560766 (P=0.0054), rs634990 (P=0.0086), and rs8032019 (P=0.0081).
      CONCLUSIONS: Our results confirm the association with refractive error at the
      15q14 locus but do not support the association observed at the 15q25 locus. Axial
      length seemed to be a major parameter at the 15q14 locus, underscoring the
      importance of this locus in myopia and future clinical treatment.

PMID- 23131719
TI  - Evaluation of a commercial Bacillus thuringiensis var. israelensis formulation
      for the control of chironomid midge larvae (Diptera: Chironomidae) in
      establishing rice crops in south-eastern Australia.
AB  - A commercial formulation of Bacillus thuringiensis var. israelensis (B.t.i.) was
      evaluated for its potential to control chironomid midge larvae in newly sown rice
      crops in south-eastern Australia. Two replicated small-plot field trials were
      conducted using product application rates of 0.5-6 kg/ha. In trial 1 application
      rates between 2 and 6 kg product/ha all significantly (P<0.05) reduced
      populations of target Chironominae/Orthocladiinae by between 71% and 93% over the
      19 day post-treatment monitoring period. Trial 2 was conducted using lower
      application rates (0.5-2 kg product/ha) and only the 2 kg product/ha rate
      significantly (P<0.05) reduced numbers of the target group (81% reduction)
      despite lower application rates resulting in target group suppression of 38-62%.
      Identification of larvae to species level from selected samples indicated that
      populations of Chironomus tepperi, the principal pest species that attacks the
      roots of rice seedlings, were reduced at all application rates; elimination of C.
      tepperi was achieved in trial 1 at an application rate of 2 kg/ha. Consistent
      with other studies, non-target Tanypodinae were not adversely affected by B.t.i.,
      and in some treatments populations of Tanypodinae exceeded control levels by up
      to 73%. In the first trial, which was conducted under relatively high pest
      pressure, plant establishment was significantly (P<0.05) increased (120-157%) by
      Vectobac(r) WDG application rates of 2-6 kg/ha. No significant increase in plant
      establishment relative to the controls was identified in the second trial, when
      pest pressure was substantially lower and minimal damage occurred in the control
      bays. Overall, our results demonstrate that B.t.i. may be an economically viable
      alternative to broad-spectrum synthetic pesticides for the control of
      phytophagous midge larvae in establishing rice crops where members of the
      Chironominae, the group most susceptible to B.t.i., are the principal species of
      concern. The high specificity of B.t.i. for nematoceran Diptera should lead to
      reduced impacts on non-target organisms.

PMID- 23131720
TI  - Enhanced Rho-kinase activity in patients with vasospastic angina after the Great
      East Japan Earthquake.
AB  - BACKGROUND: It remains unclear whether disease activity of vasospastic angina
      (VSA) is altered during a disaster. METHODS AND RESULTS: Before and after the
      Great East Japan Earthquake, we examined Rho-kinase activity in circulating
      neutrophils of 11 VSA patients and their mental stress with the post-traumatic
      stress disorder (PTSD) questionnaire. Rho-kinase activity was significantly
      increased at 6 months after the Earthquake, and was returned to baseline level at
      12 months. Importantly, percent change in Rho-kinase activity was significantly
      correlated with the PTSD score. CONCLUSIONS: These results indicate that the Rho
      kinase activity of VSA patients was transiently enhanced associated with disaster
      related mental stress.

PMID- 23131721
TI  - Novel criteria of urine osmolality effectively predict response to tolvaptan in
      decompensated heart failure patients--association between non-responders and
      chronic kidney disease.
AB  - BACKGROUND: A newly-developed vasopressin type 2 receptor antagonist, tolvaptan
      (TLV), has a unique feature of diuresis, but the response to this drug can be
      unpredictable. METHODS AND RESULTS: Data were collected from hospitalized
      patients with decompensated congestive heart failure who were administered TLV at
      3.75-15 mg/day (n=61). A responder/non-responder to TLV was determined as having
      any increase/decrease in urine volume (UV) during the next 24h after TLV
      treatment on the first day. Logistic regression analyses for increases in UV were
      performed, and independent predictors of the responder were the following: C1,
      baseline urine osmolality (U-OSM) >352 mOsm/L; and C2, %decrease in U-OSM >26% at
      4-6h after TLV administration. Criteria consisting of C1 and C2 had a good
      predictability for responders by receiver-operating characteristic analysis (area
      under the curve=0.960). Kidneys of the non-responders no longer had diluting
      ability (%decrease of U-OSM at 4-6h=2.7 +/- 14.6%*), but also barely kept
      concentrating ability (baseline U-OSM=296.4 +/- 68.7*mOsm/L) with markedly
      reduced estimated glomerular filtration ratio (35.5 +/- 29.4 m l . min(-1) . 1.73
      m(-2)*) (*P<0.05 vs. patients who had at least 1 positive condition [n=42]).
      CONCLUSIONS: More than 26% decrease in U-OSM from a baseline >352 mOsm/L for the
      first 4-6h predicts responders to TLV. Unresponsiveness to TLV is attributable to
      nephrogenic diabetes insipidus complicated by chronic renal disease.

PMID- 23131722
TI  - Improvement in door-to-balloon (D2B) time in acute ST-elevation myocardial
      infarction through the D2B alliance--experience of 15 primary percutaneous
      coronary intervention centers in Taiwan.
AB  - BACKGROUND: Currently, the door-to-balloon (D2B) times observed in clinical
      practice in Taiwan are different from those recommended by evidence-based
      guidelines. D2B Alliance, a countrywide initiative for quality supported by the
      Taiwan Joint Commission on Hospital Accreditation, sought to achieve the goal of
      administering treatment to 75% of patients with ST-elevation myocardial
      infarction (STEMI) within 90min of hospital presentation. METHODS AND RESULTS:
      The current study was designed to be prospective, national, and multicenter. We
      conducted a longitudinal study of the D2B times recorded in 15 primary
      percutaneous coronary intervention centers and examined the changes caused by
      implementing the D2B Alliance strategies. A total of 1,726 patients were enrolled
      in the D2B Alliance and implementation of the D2B Alliance strategies resulted in
      a significant decrease in the average D2B times (128.8 +/- 42.9 min vs. 83.2 +/-
      16.2 min; P<0.001) from those at baseline. By the end of the year-long study, the
      percentage of patients treated under 90 min had increased from 46.2% to 80.1% in
      the hospitals enrolled in the D2B Alliance. CONCLUSIONS: Over the 1 year,
      hospitals enrolled in the D2B Alliance achieved the goal of reducing the D2B
      times of 75% of STEMI patients to less than 90 min.

PMID- 23131723
TI  - Success and failure in integrated models of nursing for long term conditions:
      multiple case studies of whole systems.
AB  - BACKGROUND: Current projections indicate that the UK faces a 252% increase in
      people aged over 65 with one or more long term conditions (LTC) by 2050. Nurses,
      managing their own caseloads and clinics, working across sectors and
      organisational boundaries and as part of a wider multi-disciplinary team, are
      frequently seen as key to managing this growing demand. However, the evidence
      base informing the nursing role in managing LTC, the most effective configuration
      of the multi-disciplinary team and the policy evidence relating to the
      infrastructure required to support cross organisational working, remains weak.
      OBJECTIVES: To explore, identify and characterise the origins, processes and
      outcomes of effective chronic disease management models and the nursing
      contributions to such models. DESIGN: Case study whole systems analysis using
      qualitative interview methods. SETTINGS: Two community matron services, two
      primary care (GP) practice nursing services, two hospital based specialist
      nursing services were purposefully sampled from across England and Wales.
      PARTICIPANTS: Selection criteria were derived using a consensus conference. The
      nurses in the service, all patients and carers on the caseload, members of the
      multi-disciplinary team and stakeholders were invited to participate. METHODS:
      Semi-structured interviews with all participants, thematic analysis within a
      whole system framework. RESULTS: The study found high levels of clinical nursing
      expertise which in the case of the community matrons was meeting the aim of
      reducing hospital admissions. Both the primary care and hospital nurse specialist
      indicate similar levels of clinical expertise which was highly valued by medical
      colleagues and patients. Patients continued to experience fragmented care
      determined by diagnostic categories rather than patient need and by the specific
      remit of the clinic or service the patient was using. Patient data systems are
      still organised around the impact on services and prevalence of disease at an
      individual level and not around the patient experience of disease. CONCLUSION:
      Nurses are making a major contribution to meeting the policy objectives for long
      term conditions. Primary care nurses and hospital nurse specialists do broadly
      similar roles. The scope of the nursing roles and services studied were
      idiosyncratic, opportunistic and reactive, rather than planned and commissioned
      on an analysis of local population need.

PMID- 23131724
TI  - Caregiver burden--a critical discussion.
AB  - Currently, 15%, 12.8% and 17.1% of the Canadian, American and European
      populations, respectively, are 65 years or older. Due to aging-related
      disabilities, elderly individuals will require support from family members while
      in the community. Annually, family caregivers save the Canadian and American
      healthcare systems $25 billion and $350 billion, respectively. However, to
      maintain the important role they play, caregivers' experiences must be
      investigated in order to provide appropriate support. Despite the fact that
      'caregiver burden' is preponderantly used as an indicator of the caregiving
      experience, much disagreement remains on what the term entails and how it should
      be utilized. This paper endeavors to critically discuss the concept of 'caregiver
      burden', its use in the literature and the implications this has for future
      research and clinical practice. The vagueness derived from the various 'caregiver
      burden' definitions limits the term's relevance to policy-making and clinical
      practice. Additionally, much of the literature on 'caregiver burden' is not
      theoretically framed, which reduces the conceptual clarity of the term.
      Quantitative measures are largely used to investigate 'caregiver burden', which
      can sometimes fail to capture contextual features that are relevant to caregiving
      outcomes (e.g., culture). Stress theory and role theory are recommended as
      guiding frameworks for future research that investigates 'caregiver burden'.
      Future research on 'caregiver burden' would also benefit from integrating
      qualitative and quantitative approaches into mixed method designs in order to
      gain a holistic understanding of the concept.

PMID- 23131725
TI  - Monodispersed Ag3PO4 nanocrystals loaded on the surface of spherical Bi2MoO6 with
      enhanced photocatalytic performance.
AB  - Spherical Bi(2)MoO(6) nanoarchitectures with scale of 500 nm-2 MUm were prepared
      by a solvothermal reaction using bismuth nitrate and ammonium molybdate as
      precursors. Ag(3)PO(4) nanoparticles were then deposited onto the surface of
      Bi(2)MoO(6)via a facile deposition-precipitation technique. The photocatalytic
      tests display that the Ag(3)PO(4)/Bi(2)MoO(6) nanocomposites possess a much
      higher rate for degradation of rhodamine B and methylene blue than the pure
      Ag(3)PO(4) nanoparticles and Bi(2)MoO(6) under visible light. The catalytic
      activity of the composite photocatalysts is greatly influenced by the loading
      level of Ag(3)PO(4). The 50 mol% Ag(3)PO(4)-loaded Bi(2)MoO(6) spheres exhibit
      the highest photocatalytic activity in both the decolorization of RhB and MB. The
      observed improvement in photocatalytic activity is associated with the extended
      absorption in the visible light region resulting from the Ag(3)PO(4)
      nanoparticles, and the effective separation of photogenerated carriers at the
      Ag(3)PO(4)/Bi(2)MoO(6) interfaces. In addition, the composite can be easily
      reclaimed by sedimentation without any loss of its stability. Moreover, the tests
      of radical scavengers confirmed that h(+) and OH were the main reactive species
      for the degradation of RhB.

PMID- 23131726
TI  - Enhancing the activity and tuning the mechanism of formic acid oxidation at
      tetrahexahedral Pt nanocrystals by Au decoration.
AB  - Tetrahexahedral Pt nanocrystals (THH Pt NCs), bound by high index facets, belong
      to an emerging class of nanomaterials that promise to bridge the gap between
      model and practical electrocatalysts. The atomically stepped surfaces of THH Pt
      NCs are extremely active for the electrooxidation of small organic molecules but
      they also readily accommodate the dissociative chemisorption of such species,
      resulting in poisoning by strongly adsorbed CO. Formic acid oxidation is an ideal
      reaction for studying the balance between these competing catalyst
      characteristics, since it can proceed by either a direct or a CO mediated
      pathway. Herein, we describe electrochemical and in situ FTIR spectroscopic
      investigations of formic acid electrooxidation at both clean and Au adatom
      decorated THH Pt NC surfaces. The Au decoration leads to higher catalytic
      currents and enhanced CO(2) production in the low potential range. As the CO
      oxidation behaviour of the catalyst is not improved by the presence of the Au, it
      is likely that the role of the Au is to promote the direct pathway. Beyond their
      fundamental importance, these results are significant in the development of
      stable, poison resistant anodic electrocatalysts for direct formic acid fuel
      cells.

PMID- 23131727
TI  - Cross-cultural adaptation and initial validation of the Stroke-Specific Quality
      of Life Scale into the Yoruba language.
AB  - Stroke-Specific Quality of Life 2.0 (SS-QoL 2.0) scale is used widely and has
      been cross-culturally adapted to many languages. This study aimed at the cross
      cultural adaptation of SS-QoL 2.0 to Yoruba, the indigenous language of south
      western Nigeria, and to carry out an initial investigation on its validity.
      English SS-QoL 2.0 was first adapted to Yoruba language by including Yoruba
      culture-specific examples in items SC4, UE2 and UE6. The adapted English version
      (AEV) was independently translated into Yoruba by two language experts who later
      agreed on a consensus translation, which was then back translated, subjected to
      an expert committee review and pretested; a cognitive debriefing interview was
      also carried out to generate the Yoruba translated version (YTV). Thirty-five
      stroke survivors completed the AEV and Yoruba version (YV) in English and Yoruba.
      The order of administration was randomized. Data were analysed using Spearman's
      rank order correlation and Wilcoxon's signed-rank test at a P value less than
      0.05. The mean age of the participants (23 men, 12 women) was 58.5+/-11.3 years.
      The domain scores of the participants on AEV and YV did not differ significantly,
      except in the work/productivity domain. In both versions, the mean domain score
      of the participants was the highest in the language domain [22.6+/-3.8 (AEV) and
      22.7+/-3.4 (YV)] and the lowest in the work domain [9.0+/-3.7 (AEV) and 8.0+/-3.3
      (YTV)]. Domain scores on both versions correlated significantly (P<0.05).
      Participants' ratings of their current state and prestroke state correlated
      significantly (P<0.01) in all the general areas, except energy and mood. The YTV
      of SS-QoL 2.0 fulfilled the initial criteria for validity.

PMID- 23131728
TI  - How specific is a medical speciality? A semiserious game to test your
      understanding of physical and rehabilitation medicine.

PMID- 23131729
TI  - Divergently overlapping cis-encoded antisense RNA regulating toxin-antitoxin
      systems from E. coli: hok/sok, ldr/rdl, symE/symR.
AB  - Toxin-antitoxin (TA) systems are categorized into three classes based on the type
      of antitoxin. In type I TA systems, the antitoxin is a small antisense RNA that
      inhibits translation of small toxic proteins by binding to the corresponding
      mRNAs. Those type I TA systems were originally identified as plasmid
      stabilization modules rendering a post-segregational killing (PSK) effect on the
      host cells. The type I TA loci also exist on the Escherichia coli chromosome but
      their biological functions are less clear. Genetic organization and regulatory
      elements of hok/sok and ldr/rdl families are very similar and the toxins are
      predicted to contain a transmembrane domain, but otherwise share no detectable
      sequence similarity. This review will give an overview of the type I TA modules
      of E. coli K-12, especially hok/sok, ldr/rdl and SOS-inducible symE/symR systems,
      which are regulated by divergently overlapping cis-encoded antisense RNAs.

PMID- 23131730
TI  - [The peripheral mechanism of physiological pain].
AB  - Pain is defined as an unpleasant sensory and emotional experience associated with
      actual or potential tissue damage, or it is described in terms of such damage.
      Additionally, activity induced in the nociceptor and nociceptive pathways by a
      noxious stimulus is not considered pain, which is always a psychological state
      (IASP). Adelta- and C-fibers play important roles in conducting pain to the
      central nervous system. The former conducts fast pain and the latter slow pain.
      Intraneural microstimulation by microneurography causes mainly dull pain in
      glabrous skin and burning pain in hairy skin. Most of the burning pain is
      conducted by C-fibers, which are receptive to heating (CH) and are mechano- and
      heat-insensitive (CMiHi). The characters of C-fibers are easily influenced by
      chemical stimulants. For example, capsaicin induces sensitization to CMiHi and
      desensitization in the C-fibers that are mechano- and heat-responsive (CMH).
      Secondary hyperalgesia and allodynia have been shown to be the changes in the
      central network of pain, but maintenance of pain seems to require the excitation
      of nociceptors. Sensitization to heat is observed much more prominently in Adelta
      fibers than in C-fibers. Such function of Adelta-fibers is closely related to the
      maintenance of pain and spontaneous pain in the case of burn injury.
      Physiological pain has significant importance as a warning sign that ensures
      human safety.

PMID- 23131731
TI  - [Pain pathway].
AB  - In 1967, Burgess and Perl discovered nerve fibers that specifically respond to
      noxious stimuli; since then, anatomical and physiological studies in animals, as
      well as humans, conducted using microneurography and non-invasive imaging
      techniques, have shown that there are nociceptive neurons in the dorsal root
      ganglion, spinal cord, thalamus, and cerebral cortex. Further, there are 2 main
      nociceptive pathways; one comprising nociceptive specific neurons in lamina I and
      another comprising wide dynamic range neurons in lamina V in the dorsal horn of
      the spinal cord. However, the roles of the 2 pathways in pain perception are
      still largely unknown. In this brief review, I intended to consider whether and
      how putative structures in the nociceptive pathway contribute to pain perception.

PMID- 23131732
TI  - [Neuropathy and unmyelinated epidermal nerve fibers].
AB  - Detection of unmyelinated epidermal nerve fibers allows objective, pathologic,
      and minimally invasive assessment of small myelinated A-delta and unmyelinated C
      primary afferent fibers. This procedure is especially valuable for diagnosing
      small fiber neuropathy; this condition is characterized by sensory symptoms and
      pain in the lower extremities but standard nerve conduction fails to show
      abnormalities in this condition. Detection of epidermal nerve fibers is useful
      not only for confirming the diagnosis of neuropathies affecting small-diameter
      sensory fibers, but also in advanced clinical care since this procedure can
      provide insights into the role of small myelinated and unmyelinated axons in
      peripheral nerve disorders and neuropathic pain. In this review, we discuss
      standard technical aspects of skin biopsy introduced for evaluation of epidermal
      nerve fibers and the feasibility of skin biopsy for diagnosing small fiber
      neuropathy and neuronopathy. We also describe the usefulness of skin biopsy in
      diagnosing peripheral neuropathies and other neurological disorders.

PMID- 23131733
TI  - [Role of the glia in neuropathic pain caused by peripheral nerve injury].
AB  - Neuropathic pain is often a consequence of nerve injury due to surgery, cancer,
      bone compression, diabetes, or infection. This type of pain can be so severe that
      even the slightest touch can cause intense pain in the affected area. Neuropathic
      pain is generally resistant to currently available treatments. Abundant evidence
      in the literature suggests that activated microglia and astrocytes are key
      players in neuropathic pain and that ATP receptors expressed in the glia have an
      important role in pain signaling. In this review, we summarize the roles of the
      microglia in the functioning of ATP receptors and of the astrocytes in
      neuropathic pain. Understanding the key functions of the microglia and astrocytes
      may lead to the development of new strategies for the management of intractable
      chronic pain.

PMID- 23131734
TI  - [Neuronal mechanisms underlying pain-induced negative emotions].
AB  - Pain consists of sensory-discriminative and negative emotional components.
      Although the neuronal basis of the sensory component of pain has been studied
      extensively, the neuronal mechanisms underlying the negative emotional component
      are not well understood. Recently, behavioral studies using a conditioned place
      paradigm have successfully elucidated the neuronal circuits and mechanisms
      underlying the negative emotional component of pain. Excitotoxic lesions of the
      anterior cingulate cortex (ACC), central amygdaloid nucleus, basolateral
      amygdaloid nucleus (BLA), or bed nucleus of the stria terminalis (BNST) suppress
      intraplantar formalin-induced aversive responses. Glutamatergic transmission
      within the ACC and BLA via N-methyl-D-asparate (NMDA) receptors has been shown to
      play a critical role in these aversive responses. In the BNST, especially its
      ventral part, noradrenergic transmission via beta-adrenergic receptors has been
      shown to be important for pain-induced aversion. Because persistent pain is
      frequently associated with psychological and emotional dysfunctions, studies on
      the neuronal circuits and molecular mechanisms involved in the negative emotional
      component of pain may have considerable clinical importance in the treatment of
      chronic pain. Here, I have reviewed behavioral studies investigating the neuronal
      mechanisms underlying the negative emotional component of pain and have
      introduced our data showing the pivotal role of amygdala and BNST in pain-induced
      aversion.

PMID- 23131735
TI  - [Pathophysiology of neuropathic pain: Na+ channel and hyperexcitability of
      primary afferents].
AB  - Neuropathic pain occurs as a result of peripheral neuropathy or peripheral nerve
      injury. Voltage-gated Na+ channels are assumed to play a major role in the
      pathophysiology of neuropathic pain and have become important therapeutic
      targets, because they are critical determinants of the excitability of sensory
      neurons. Nerve injury or disease could induce changes in trafficking, gene
      expression, and kinetics of Na+ channels, resulting in ectopic discharge and
      increased neuronal excitability. Hyperexcitability of neurons and excess
      discharge lead to neuropathic pain and trigger central sensitization. Four
      isoforms of Na+ channels, Na+1.3, 1.7, 1.8, and 1.9, have been implicated in the
      pathogenesis of neuropathic pain. However, it is unclear whether the
      pharmacological target should be a single isoform or a complex of isoforms. Na+
      channel blockers could stabilize the axonal membrane and suppress pain sensation.
      However, adverse side effects, such as somnolence, nausea, and vertigo, resulting
      from the suppression of neural activity in the central nervous system, are
      practical limitations on the systemic administration of Na+ channel blockers.
      Agents such as subtype-specific antagonists or drugs that cannot cross the blood
      brain barrier could be candidates for novel drugs in pain treatment. Na+ channels
      are attractive targets for studying the pathophysiology of neuropathic pain and
      for drug development. However, recent advances have been mostly based on basic
      research. Overcoming the challenges in directly approaching patients with
      neuropathic pain might advance our understanding of the pathophysiology of pain
      and aid the development of therapeutic strategies.

PMID- 23131736
TI  - [Pathophysiology of neuropathic pain: molecular mechanisms underlying central
      sensitization in the dorsal horn in neuropathic pain].
AB  - Neuropathic pain syndromes are clinically characterized by spontaneous pain and
      evoked pain (hyperalgesia and allodynia). The optimal treatment approach for
      neuropathic pain is still under development because of the complex pathological
      mechanisms underlying this type of pain. The spinal cord is an important gateway
      thorough which peripheral pain signals are transmitted to the brain, and
      sensitization of the spinal neurons is one of the important mechanisms underlying
      neuropathic pain. Central sensitization represents enhancement of the function of
      neuronal circuits in nociceptive pathways and is a manifestation of the
      remarkable plasticity of the somatosensory nervous system after nerve injury.
      This review highlights the pathological features of central sensitization, which
      develops because of (1) injury-induced abnormal inputs from primary afferents,
      (2) increase in the excitability of dorsal horn neurons, and (3) activated glial
      cell-derived signals.

PMID- 23131737
TI  - [Neuroimaging findings of central nervous system dysfunction in neuropathic
      pain].
AB  - The central mechanism of pain is influenced by multiple factors including the
      quality of stimulation, cognition, psychological status, environment, and
      genetics. The region of the brain modulated by painful sensation, taken together,
      are termed as "pain matrix," composing primary/secondary somatosensory area,
      thalamus, insula, prefrontal cortex, anterior cingulate cortex, basal ganglia,
      limbic system, brainstem, and cerebellum. The degrees of noxious stimulation and
      chronic spontaneous pain are associated with activity in the insula and the
      anterior cingulate cortex, which is involved in the emotional dimension of pain.
      Brain activation by allodynia is observed in the thalamus, prefrontal cortex,
      anterior cingulate, insula, and cerebellum and relates to attention and sensory
      motor integration. Molecular neuroimaging studies indicate that the underlying
      pathophysiology of pain is related to the dopaminergic system, opioidergic
      system, and brain inflammation. Functional neuroimaging can elucidate the
      pathophysiology of acute and chronic pain syndromes, and thus objectively
      evaluate the degree of pain sensation, enabling us to plan pain control therapies
      for the future.

PMID- 23131738
TI  - [Tips for taking history of pain].
AB  - Pain is physiologically classified as nociceptive pain, neuropathic pain, and
      psychogenic pain. Nociceptive pain is further divided into visceral pain, somatic
      pain, and referred pain. Visceral pain is dull, and it is difficult to locate the
      origin of such pain. Somatic pain is sharp, severe, and well localized. On
      receiving visceral input for pain, it affects somatic nerve inputting to the same
      spinal segments, then referred pain is felt in the skin and muscles supplied by
      it. Referred pain is felt in an area that is located at a distance from its
      cause. History taking is the most important factor for determining the cause of
      pain. Generally, all the necessary information regarding pain can be acquired if
      pain-related history is obtained using the "OPQRST" mnemonic, that is, onset,
      provocation/palliative factor, quality, region/radiation/related symptoms,
      severity, and time characteristics.

PMID- 23131739
TI  - [Pharmacological treatment strategy and mirror visual feedback treatment for
      neuropathic pain].
AB  - Neuropathic pain is a debilitating condition, and pharmacotherapy is the most
      established treatment strategy. A variety of pharmacotherapies is used for
      neuropathic pain management: however, pharmacotherapies with evidence for
      analgesic potency are less common. Several pharmacotherapeutic treatment
      guidelines for neuropathic pain treatment recommend the first- to third-line
      drugs on the basis of evidence-based medicine; however, neuropathic pain is often
      resistant to pharmacotherapies. We have treated pharmacotherapy-resistant
      neuropathic pain with neurorehabilitation techniques such as mirror visual
      feedback (MVF) treatment. Further to our clinical experience using MVF, we
      discuss the cerebral mechanism associated with neuropathic pain in this study.

PMID- 23131740
TI  - [Clinical characteristics and multidisciplinary management of chronic
      musculoskeletal pain].
AB  - Musculoskeletal disorders are the most common causes of severe long-term pain and
      physical disability, affecting hundreds of millions of people around the world.
      In industrialized countries, which have increasingly aging populations, chronic
      musculoskeletal pain has become a significant health care burden and major issue
      in the 1980s and 1990s. On January 13, 2000, The Bone and Joint Decade was
      formally launched at the headquarters of the World Health Organization in Geneva,
      Switzerland. This global campaign aimed to improve the quality of life for people
      who have musculoskeletal conditions. Complying with this trend, large-scale
      surveys have been conducted in Europe and the US in recent years to evaluate the
      effect of chronic pain on society, but in Japan, there has been a paucity of
      basic information on the status of chronic musculoskeletal pain. We organized a
      postal survey designed to quantify and describe the prevalence and distribution
      of chronic pain in the Japanese community. We found that chronic pain of moderate
      to severe intensity occurs in 17.2%. Chronic pain had a significant impact on the
      occupational and social relationships, and it seriously affected their
      psychological conditions and quality of life. Such disabling chronic pain is
      regarded as the result of interrelated physical, psychological, and social or
      occupational factors requiring multidisciplinary intervention. We introduce a
      multidisciplinary clinical approach and report on novel multimodal methodologies 
      - for patients with chronic musculoskeletal pain.

PMID- 23131741
TI  - [Actual effectiveness of nerve block against neuropathic pain].
AB  - Evidence regarding the effectiveness of nerve block in treating neuropathic pain
      is scarce. However, in actual clinical situations, nerve block has been used as a
      treatment in combination with other methods, such as pharmacotherapy,
      psychotherapy, and physiotherapy. The goal of neuropathic pain treatment is not a
      complete recovery but some improvement in the activities of daily living (ADL) as
      well as the quality of life. There is no single effective, definitive treatment
      for the various causes of neuropathic pain; therefore, the active use of nerve
      block should be considered in patients who show a positive response to this
      treatment. This is because nerve block reduces pain and improves the patients'
      ADL. Nerve block also has the potential to be effective as an early treatment of
      and prophylaxis for neuropathic pain. Therefore, the use of nerve block should be
      considered from the onset of pain. In recent years, methods such as ultrasound
      guided nerve block and thermocoagulation with pulsed radiofrequency have become
      more commonly used as safer and more accurate nerve block techniques. This
      article discusses the current clinical status of nerve block against neuropathic
      pain.

PMID- 23131742
TI  - [Surgical procedures for neuropathic pain].
AB  - Different surgical procedures are available for the treatment of many neuropathic
      pain syndromes. These surgical procedures can be divided into 2 main sections:
      non-destructive and destructive procedures. In recent years, the non-destructive
      neurostimulation method has undergone rapid development. Neurostimulation can be
      applied to a large part of the nervous system including the brain, spinal cord,
      and peripheral nerves. Spinal cord stimulation has become a dominant pain relief
      modality because of its minimal invasiveness and the development of a multi
      contact stimulating electrode system powered by a multi-programmable and
      rechargeable stimulator. Currently, destructive surgical procedures have a
      limited range of indications for pain control. However, the advantages of
      destructive procedures over non-destructive ones include continuous pain
      reduction without implantation of a stimulation system. Each of the surgical
      procedures has great potential for providing patients with significant relief
      from neuropathic pain.

PMID- 23131743
TI  - [Diagnosis and treatment of chronic pain by pain clinicians].
AB  - Pain is classified into physical and psychological pain. Physical pain is
      nociceptive, inflammatory, or neuropathic. Pain can be categorized into acute or
      chronic pain depending on the duration of pain and mechanism of onset. Acute pain
      heals as the underlying cause is resolved and includes naturally curable
      nociceptive and potentially curable neuropathic pain. Chronic pain is caused by
      incurable conditions or requires a long time to heal and is persistent: it
      includes chronic nociceptive pain, established neuropathic pain, and psychogenic
      pain. The therapeutic strategies for pain depend on the underlying pathological
      conditions: (1) For nociceptive pain, analgesics, narcotic analgesics, and nerve
      block are indicated. (2) For neuropathic pain, supplementary analgesics, but not
      analgesics, are indicated, and some narcotic analgesics are also effective: the
      recommended supplementary analgesics include calcium channel alpha-2-delta
      ligands, tricyclic antidepressants (TCAs), and serotonin-noradrenaline reuptake
      inhibitors (SNRIs). (3) For psychogenic pain, analgesics and nerve block are not
      indicated, except in the setting of a placebo effect: in paticular, narcotic
      analgesics should not be used. Psychological therapy, tranquilizer
      administration, cognitive behavior therapy, and patient education are indicated
      for this kind of pain.

PMID- 23131744
TI  - [Psychiatric issues in chronic pain].
AB  - Pain is a common reason for seeking health care and chronic pain is a common
      comorbidity in psychiatric disorders. In clinical practice, we encounter many
      patients with chronic pain; however, before initiating pain treatment, we should
      conduct detailed analysis of psychiatric symptoms, such as perception, memory,
      thought and mood disturbances or behavioral problems. We should also determine
      the frequency of occurrence of mental disorders in patients with pain, especially
      those with chronic pain, such as in mood, anxiety, pain, personality, and
      developmental disorders, and dementia. Current understanding of the intricate
      relationship between chronic pain and psychiatric issues not only provides
      opportunities for designing appropriate treatment but also raises good and new
      questions for future pain research.

PMID- 23131745
TI  - [The corticospinal tract and its role in motor control].
AB  - The corticospinal tract (CST) makes a direct connection to the motor neurons of
      the hand muscles in higher primates. The existence of such a "phylogenetically
      new" direct pathway has been regarded as the basis of highly developed
      fractionated finger movements in these species. In contrast, in lower mammalian
      species such as carnivores and rodents, the direct connection does not exist.
      Instead, the shortest pathway is disynaptic and mediated by propriospinal neurons
      (PNs) around the C3-C4 segments. Previously, the existence and role of the PN
      mediated pathway in primates was not well established. We first demonstrated the
      existence of the pathway in macaque monkeys. Then, to assess its function, we
      made specific lesions of the CST at the C4/C5 level to interrupt the direct
      pathway. Surprisingly, the monkey recovered the fractionated finger movements
      within several weeks, while the hand dexterity did not recover after a lesion at
      C2. These results suggest that the PNs can take over the function of the direct
      pathway, and control precision grip. However, such findings indicate that the PNs
      can be involved in the recovery after CST lesion, but their function in the
      intact state is not clear. To clarify the normal function of the PNs, we recently
      developed a pathway-selective and reversible transmission blocking technique
      using a combination of two viral vectors that induce expression of enhanced
      tetanus neurotoxin (eTeNT) in the PNs during administration of doxycycline with
      the Tet-ON system. Induction of eTeNT expression resulted in an impairment in
      reaching and precision grip, suggesting a critical role of the PN-mediated
      indirect pathway in the control of finger dexterity.

PMID- 23131746
TI  - [A survey of psychiatrists to determine their level of familiarity with anti-N
      methyl-D-aspartate receptor encephalitis].
AB  - As anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis develops with
      incipient psychiatric symptoms in most patients, they initially seek medical care
      at psychiatric services. It would be desirable, therefore, for psychiatrists to
      be well aware of anti-NMDAR encephalitis. From this point of view, we conducted a
      questionnaire survey of psychiatrists to explore the present status of their
      level of awareness about anti-NMDAR encephalitis. A questionnaire survey of 115
      psychiatrists engaged in medical care in Toyama Prefecture was conducted to
      explore their level of familiarity with anti-NMDAR encephalitis. Responses to the
      questionnaire were received from 76 psychiatrists (response collection rate
      66.1%). The mean tenure in the medical profession was 23.5 +/- 13.8 years for the
      76 psychiatrists, of whom 61 (80.3%) were psychiatric specialists. As for the
      level of awareness of anti-NMDAR encephalitis, there were 37 doctors (48.7%) who
      were "not aware of this disorder," 23 (30.3%) who were "aware of only the name of
      this disorder," and 16 (21.0%) who had "knowledge of an outline of this
      disorder." While the level of familiarity of doctors with "knowledge of an
      outline of this disorder" was unrelated to whether the doctor was a specialist,
      the tenure in the medical profession was significantly shorter for these doctors
      than for the others (P < 0.05). Of the doctors who were "not aware of this
      disorder" and those who were "aware of only the name of this disorder," a high
      percentage comprised physicians working at hospitals/clinics specializing in
      psychiatry (P < 0.05). Only 7 doctors had encountered case(s) of anti-NMDAR
      encephalitis (9.2%), and among them, a significantly high percentage was on the
      staff of polyclinic hospitals (P < 0.05). The present survey revealed low levels
      of familiarity of psychiatrists with anti-NMDAR encephalitis, and this highlights
      the importance of further improving the awareness of psychiatrists about the
      concept of anti-NMDAR encephalitis.

PMID- 23131747
TI  - [Primary central nervous system lymphoma: a case report and evaluation of the
      diagnostic value of IL-10 level in the cerebrospinal fluid].
AB  - We report a case of primary central nervous system lymphoma (PCNSL) that
      presented with visual disturbance. A 76-year-old man developed decreased
      bilateral visual acuity. He was diagnosed with bilateral retrobulbar neuritis by
      an ophthalmologist. Treatment with high-dose corticosteroids was initiated and
      resulted in mild improvement of visual acuity. However, the patient gradually
      became apathetic and bradykinetic, experiencing difficulty performing the
      activities of daily living; he was admitted to our hospital because of this
      progressive illness. Neurological examination revealed bradyphrenia and
      bradykinesia with frontal lobe release signs, disorientation, and ideomotor
      apraxia. Magnetic resonance imaging showed abnormal signals in the bilateral
      basal ganglia and thalamus. Cerebrospinal fluid (CSF) examination revealed no
      pleocytosis and slightly elevated protein levels: beta2-microglobulin level was
      mildly increased, and IL-10 level in the CSF was markedly elevated. These
      findings suggested a diagnosis of PCNSL, and a brain biopsy specimen was obtained
      from the left caudate head. Pathological findings indicated diffuse large B-cell
      lymphoma. Nonspecific neurological manifestations and radiological findings can
      make the diagnosis of PCNSL difficult and result in delayed diagnosis. Visual
      impairment has been suggested as a feature of PCNSL, and an elevated IL-10 level
      in the CSF may be a useful marker for diagnosing PCNSL.

PMID- 23131748
TI  - Myelination: do astrocytes play a role?
AB  - Astrocytes are the most abundant cell type in the adult central nervous system
      (CNS), and their functional diversity in response to injury is now being
      appreciated. Astrocytes have long been considered the main player in the
      inhibition of CNS repair via the formation of the gliotic scar, but now it is
      accepted that astrocyte can play an important role in CNS repair and
      remyelination. Interest in the relationship between astrocytes and myelination
      focused initially on attempts to understand how the development of plaques of
      astroglial scar tissue in multiple sclerosis was related to the failure of these
      lesions to remyelinate. It is now considered that this is an end stage
      pathological response to injury, and that normally astrocytes play important
      roles in supporting the development and maintenance of CNS myelin. This review
      will focus on how this new understanding may be exploited to develop new
      strategies to enhance remyelination in multiple sclerosis and other diseases. 

PMID- 23131749
TI  - Destructive rib lesions in an HIV sero-negative male: an unusual presentation of
      tuberculosis in a high tuberculosis prevalence setting.
AB  - Tuberculosis (TB) of the rib is a very rare form of skeletal TB and its diagnosis
      may be difficult because of a low index of suspicion by clinicians. The
      presentation often mimics malignant disease clinically and radiologically and
      diagnosis may only be confirmed by tissue biopsy. We present a 32-year-old HIV
      negative man who presented with a three-month history of progressively worsening
      pleuritic chest pain, weight loss, fatigue, anorexia and low-grade fever with
      night sweats. A chest computerized tomography (CT) scan showed destructive
      lesions in the right fourth and seventh ribs with no pulmonary lesions. A
      diagnosis of TB of the rib was made after surgical resection and histopathology
      of the affected tissue. There was significant improvement when anti-TB therapy
      was initiated. This case report emphasizes the importance of a high index of
      suspicion of TB in patients presenting with destructive bone lesions in regions
      with high prevalence of TB.

PMID- 23131750
TI  - Use of a Fogarty catheter after tracheobronchial inhalation of a bead.
AB  - We describe a case of tracheobronchial inhalation of a bead by a five-year-old
      girl in Djibouti. The bead was extracted using a Fogarty balloon catheter passed
      through the rigid bronchoscope without complication. This kind of accident is not
      exceptional and we discuss the management of such cases with limited diagnostic
      tools and therapeutic environments.

PMID- 23131751
TI  - Review of cardiopulmonary resuscitation was of limited value.

PMID- 23131752
TI  - Influence of H2SO4 and ferric iron on Cd bioleaching from spent Ni-Cd batteries.
AB  - The paper is concerned with biohydrometallurgical methods of cadmium recovery
      from spent Ni-Cd batteries. Cd leaching efficiency from electrode material in
      different media (H(2)SO(4) and Fe(2)(SO(4))(3) solutions), at different Fe(III)
      concentrations and using the bacteria Acidithiobacillus ferrooxidans were
      investigated. The main aim of this study was to understand which from the
      bioleaching products (sulphuric acid or ferric sulphate) play a main role in the
      bioleaching process of Cd recovery. The influence of Fe ions on Cd leachability
      was confirmed. The best leaching efficiency of Cd (100%) was reached by
      bioleaching and also by leaching in Fe(2)(SO(4))(3) solution. The results of X
      ray diffraction confirmed that no cadmium was present in solid residuum obtained
      after the Cd bioleaching as well as Cd leaching using solely ferric iron. The use
      of H(2)SO(4) solution resulted in the lowest efficiency of Cd leachability, the
      presence of hydroxides in electrode materials caused neutralization of the
      leaching solution and inhibition of Cd leaching.

PMID- 23131754
TI  - Cyanoacrylate glues for wilderness and remote travel medical care.
AB  - Cyanoacrylate (CA) glues are commonly used in medical and household repairs.
      Their chemical compositions have been refined over half a century, making some
      more suitable than others for creative applications. In remote settings where
      advanced medical care is not accessible, readily available CAs of differing
      chemical composition may possess an important therapeutic function. Within this
      paper we critically examine the published therapeutic risks and benefits of both
      pharmaceutical and hardware grade CAs when applied in acute care situations.
      Topics discussed include wound closure as well as the treatment of burns,
      abrasions, and blisters. Also considered are their chemical properties,
      toxicities, and potential off-label uses.

PMID- 23131755
TI  - Increase in older adults reporting mountaineering-related injury or illness in
      the United States, 1973-2010.

PMID- 23131756
TI  - Initial assessment of the ability of ivermectin to kill Ixodes scapularis and
      Dermacentor variabilis ticks feeding on humans.
AB  - OBJECTIVE: The purpose of this study was to determine Ixodes scapularis and
      Dermacentor variabilis tick mortality when fed on humans who have consumed 400
      MUg/kg oral ivermectin. METHODS: Six study subjects, 3 in each group, were
      randomly assigned to receive either 400 MUg/kg ivermectin or placebo in a blinded
      manner. After consuming either ivermectin or placebo, each study subject had 2
      colostomy bags attached to his or her abdomen. One of the colostomy bags
      contained 7 I scapularis nymphs and 7 adults. The other colostomy bag contained 7
      D variabilis nymphs and 7 adults. Tick mortality was recorded over the next 24
      hours. RESULTS: Fifty-five percent (6 of 11) of the attached I scapularis nymphs
      exposed to ivermectin had morbidity (3 of 11) or died (3 of 11), compared with 0%
      morbidity and mortality in the 2 I scapularis nymphs that attached in the placebo
      group. No I scapularis adults or D variabilis nymphs attached to feed. Among D
      variabilis adults that attached to feed, there was a 0% mortality rate for both
      the placebo group (0 of 6) and the ivermectin group (0 of 8). CONCLUSIONS: We
      demonstrate a novel method to confine ticks to human subjects to study tick-borne
      diseases. While there was a trend toward I scapularis morbidity and mortality in
      the ivermectin arm, the low number of ticks that attached in the placebo group
      limited our analysis. Most ticks began feeding in the last 12 hours of the
      experiment, significantly limiting their exposure to ivermectin. Ivermectin does
      not cause early death in D variabilis adults.

PMID- 23131757
TI  - Glial cell line-derived neurotrophic factor modulates the excitability of
      nociceptive trigeminal ganglion neurons via a paracrine mechanism following
      inflammation.
AB  - Previous our report indicated that acute application of glial cell line-derived
      neurotrophic factor (GDNF) enhances the neuronal excitability of adult rat small
      diameter trigeminal ganglion (TRG) neurons, which innervate the facial skin in
      the absence of neuropathic and inflammatory conditions. This study investigated
      whether under in vivo conditions, GDNF modulates the excitability of nociceptive
      Adelta-TRG neurons innervating the facial skin via a paracrine mechanism
      following inflammation. We used extracellular electrophysiological recording with
      multibarrel-electrodes in this study. Spontaneous Adelta-TRG neuronal activity
      was induced in control rats after iontophoretic application of GDNF into the
      trigeminal ganglia (TRGs). Noxious and non-noxious mechanical stimuli evoked
      Adelta-TRG neuronal firing rate were significantly increased by iontophoretic
      application of GDNF. The mean mechanical threshold of nociceptive TRG neurons was
      significantly decreased by GDNF application. The increased discharge frequency
      and decreased mechanical threshold induced by GDNF were antagonized by
      application of the protein tyrosine kinase inhibitor, K252b. The number of Adelta
      TRG neurons with spontaneous firings and their firing rates in rats with
      inflammation induced by Complete Freund's Adjuvant were significantly higher than
      control rats. The firing rates of Adelta-TRG spontaneous neuronal activity were
      significantly decreased by iontophoretic application of K252b in inflamed rats.
      K252b also inhibited Adelta-TRG neuron activity evoked by mechanical stimulation
      in inflamed rats. These results suggest that in vivo GDNF enhances the
      excitability of nociceptive Adelta-TRG neurons via a paracrine mechanism within
      TRGs following inflammation. GDNF paracrine mechanism could be important as a
      therapeutic target for trigeminal inflammatory hyperalgesia.

PMID- 23131758
TI  - Ventricular aneurysms are different from ventricular diverticula!

PMID- 23131759
TI  - Idiopathic ventricular fibrillation, early repolarization and other J wave
      related ventricular fibrillation syndromes: from an electrocardiographic enigma
      to an electrophysiologic dogma.
AB  - Current clinical and experimental data demonstrate that the electrocardiographic
      J wave plays a critical role in the pathogenesis of ventricular fibrillation (VF)
      in patients with Brugada syndrome (BS) and early repolarization (ER) syndrome
      (ERS). This has generated renewed interest in the presence of J waves and ERS in
      the general population, yet the identification of high-risk ECG markers and the
      risk stratification of subjects with ERS remain to be established. More recently,
      this concept has been expanded to VF mechanisms in patients with structural heart
      diseases. Some of the fatal arrhythmias in the setting of acute myocardial
      ischemia or infarction may share a similar, J wave-related electrophysiologic
      process. In canine arterially perfused wedge preparations, the occurrence of J
      wave-related arrhythmias is mediated by phase 2 reentry. The stability of the
      action potential (AP) dome in the ventricular epicardium is dependent on the
      prominence of the AP phase 1 notch. The ability to maintain the AP dome depends
      on a delicate balance between inward and outward ionic currents during
      depolarization and the early phase of repolarization. Outward shifts of the
      balance and inability to maintain the AP dome result in marked dispersion of
      repolarization and vulnerability to VF. This review describes the
      electrocardiographic and clinical features of the J waves in idiopathic VF and
      other structural heart diseases.

PMID- 23131760
TI  - Ventricular aneurysms are different from ventricular diverticula!

PMID- 23131761
TI  - Will diagnosing polyvascular disease in coronary heart disease patients improve
      their outcomes?

PMID- 23131762
TI  - Preparation and evaluation of C10-cationic latex particle coated open-tubular
      column for capillary electrochromatography.
AB  - A simple way was proposed to prepare reverse phase open tubular column (OTC) for
      capillary electrochromatography (CEC) by dynamically coating cationic latex
      particles with C(10) functional groups onto the fused silica capillary with
      surface sulphonation. The latex particles are bounded into the capillary wall via
      electrostatic attraction force and demonstrate good stability under test
      conditions. Relative bare silica capillary, reverse electroosmotic flow (EOF) is
      generated for the OTC due to the existence of cationic latex particles onto the
      capillary. Preliminary separation of aromatic compounds on an OTC with 50 i.d.
      has been demonstrated.

PMID- 23131763
TI  - Macroporous polymer monoliths as second dimension columns in comprehensive two
      dimensional gas chromatography: a feasibility study.
AB  - When the typical column combinations are used, comprehensive two-dimensional gas
      chromatography (GC*GC) suffers from the impossibility to operate both dimensions
      at their optimum carrier gas velocities at the same time. This as a result of the
      flow mismatch caused by the different dimensions of the columns used. The
      objective of the present study was the development of monolithic second dimension
      columns which would allow simultaneous optimum-velocity operation. With
      monolithic GC columns the optimum performance can be obtained at any given flow
      rate by varying the bed structure and column diameter. Different divinylbenzene
      based monolithic columns were prepared and evaluated in terms of permeability and
      performance. Plate heights of less than 0.18 mm and plate generation rates up to
      600 plates/s were achieved. 1D-GC experiments performed on short monolithic
      columns showed a good resolving power thanks to the elevated retention and the
      good selectivity. A peak capacity up to 12 peaks per 4-5s was obtained for low
      boiling alkanes, confirming the potential for fast separations. Excellent
      repeatability in terms of retention times (RSD<0.5%) and peak widths (RSD<1.5%)
      was observed. The columns prepared were successfully used in the second dimension
      of a GC*GC setup with a standard non-polar first dimension. Model experiments
      proved the possibility to operate both dimensions at their optimum linear
      velocity simultaneously. The suitability of the novel second dimension column
      format to perform multidimensional separations was shown for selected
      applications.

PMID- 23131764
TI  - Substrateless graphene fiber: a sorbent for solid-phase microextraction.
AB  - In current study, a substrateless graphene fiber was successfully prepared by a
      simple hydrothermal strategy and used as solid-phase microextraction (SPME)
      sorbent. Five organochlorine pesticides (OCPs) were employed as model analytes to
      evaluate the performance of as-prepared graphene fiber. The results showed that
      the graphene fiber exhibited higher extraction efficiencies, higher thermal
      stability (up to 310 degrees C), better reproducibility, and longer service life
      (more than 180 times reuse) than commercial fibers. In addition, the method for
      the determination of OCPs was proposed by coupling headspace (HS)-SPME technique
      with gas chromatography/electron capture detector (HS-SPME-GC/ECD). The proposed
      HS-SPME-GC/ECD method showed low limits of detection (0.83-11.5 ng/L), wide
      linear dynamic ranges (more than 2 orders of magnitude), and acceptable
      reproducibility (RSD<10.9%). Finally, the proposed method was successfully
      applied to the analysis of OCPs in environmental water samples with good
      recoveries (81-121%) and satisfactory precisions (RSD<9%).

PMID- 23131765
TI  - Cytotoxic cholestane-type and ergostane-type steroids from the aerial parts of
      Euphorbia altotibetic.
AB  - Phytochemical investigation of the ethanol extract obtained from the aerial parts
      of the Euphorbia altotibetic PAULS. Grown in China resulted in the isolation of
      three new cholestane-type and three new ergostane-type steroids (cholest-5-en
      2beta, 4beta-diol; cholest-5-en-1beta, 4beta-diol; cholest-5-en-1alpha, 3beta,
      4alpha -triol; (22E)-ergosta-7,9,22-trien- 3beta-ol beta-D-glucoside; 5alpha
      methoxy-(22E)-ergosta-7,9,22-trien-3beta-ol beta-D-glucoside; 6beta- methoxy
      (22E)-ergosta-7,9,22-trien-3beta-ol beta-D-glucoside), along with seven known
      compounds. Their structures were established by extensive one- and two
      dimensional NMR spectroscopy, as well as other spectrum and chemical analysis.
      The isolated new steroids exhibited potent anti-tumor activity against the HeLa
      cell and Hep-G2 cell with the 50% inhibiting concentration values ranging from
      1.9 to 9.2 MUg/mL.

PMID- 23131768
TI  - Safety during breastfeeding: drugs, foods, environmental chemicals, and maternal
      infections.
AB  - The two ultimate goals of using maternal medications during breastfeeding are (i)
      to provide definitive therapy for maternal conditions for which the drugs have
      been prescribed, and (ii) to assure protection of the nursing infant from any
      adverse event related to his/her mother's treatment. Fortunately there are only a
      few drugs that have been identified as potentially causing harm to the infant.
      Analytic techniques exist to measure compounds in concentrations as small as
      nanograms per liter of milk. For nearly all compounds these very small amounts
      would not be able to exert pharmacological activity, even if absorbed by the
      infant via the oral route. For environmental chemicals, this ability to measure
      very small amounts exceeds our knowledge of any biological activity. Concern over
      any possible adverse event to the nursing infant should take into account the
      drug, its dose, the age of the infant, recognition of the interindividual
      variation in drug response and the role of pharmacogenetics. The latter two
      variables are closely linked.

PMID- 23131769
TI  - Survivin promoter polymorphisms and autoantibodies in endometriosis.
AB  - Expression of survivin, an inhibitor of apoptosis, is increased in endometriotic
      lesions and probably favors the survival of endometrial fragments in the
      peritoneal cavity. The aim of this study was to evaluate associations between
      survivin promoter polymorphisms and the risk of endometriosis, as well as to
      compare the immunoreactivity to survivin in sera of patients with and without
      endometriosis. We studied 149 women with endometriosis, 196 fertile women from
      the general population (control group A) and 47 women who had undergone
      diagnostic laparoscopy and had no evidence of endometriosis (control group B).
      There were no significant differences in the genotypic distribution of the
      survivin gene promoter region -241C/T, -235G/A and -31G/C single nucleotide
      polymorphisms (SNP) between endometriosis patients and the two control groups. In
      addition, also median anti-survivin autoantibody levels were similar among
      patients and controls (group B). However, anti-survivin antibody concentrations
      seemed to be influenced by cigarette smoking, being significantly lower in sera
      of actively smoking women compared to non-smokers (median OD: 0.019 vs. 0.155,
      respectively, P<0.001), and by the -235G/A SNP, as A allele carriers were
      significantly more frequent among women with a high antibody level (OD>=2.0)
      compared to those with lower concentrations (OD<2.0) (23.1% vs. 4.1%,
      respectively, P=0.008). Based on these results, we conclude that survivin
      promoter polymorphisms are not associated with susceptibility to endometriosis in
      the Estonian population, and though the expression of survivin is increased in
      endometriotic lesions, autoimmune reactivity against it is similar in women with
      and without the disease.

PMID- 23131770
TI  - Immunological and biochemical markers in preeclampsia.
AB  - A basic precondition for the development of preeclampsia is the presence of
      placental trophoblast cells in the maternal blood circulation. On the other hand,
      while trophoblast cells are present in the blood of all pregnant women,
      preeclampsia occurs in only 2-5% of them. Evidently, other factors play a crucial
      role. The aim of this study was to compare a set of selected immunological
      factors (anti-cardiolipin autoantibodies, trophoblast-induced cell-mediated
      immunity, C3 and C4 complement components) and biochemical factors (serum
      immunoglobulins IgA, IgG, IgM) among three groups of women with uncomplicated
      pregnancy, gestational hypertension, or preeclampsia. Blood samples were taken 2
      12h before delivery. In the preeclampsia group, there was a significantly higher
      number of women positive for anti-cardiolipin autoantibodies, trophoblast-induced
      cell-mediated immunity was elevated, serum IgG was elevated and C4 complement
      component was reduced. We conclude that both elevated autoimmune reactivity and
      the higher immune reactivity to trophoblast may contribute to the onset of
      preeclampsia.

PMID- 23131771
TI  - Annexin A2 and PSF proteins interact with p53 IRES and regulate translation of
      p53 mRNA.
AB  - p53 mRNA has been shown to be translated into two isoforms, full-length p53 (FL
      p53) and a truncated isoform DeltaN-p53, which modulates the functions of FL-p53
      and also has independent functions. Previously, we have shown that translation of
      p53 and DeltaN-p53 can be initiated at Internal Ribosome Entry Sites (IRES).
      These two IRESs were shown to regulate the translation of p53 and DeltaN-p53 in a
      distinct cell-cycle phase-dependent manner. Earlier observations from our
      laboratory also suggest that the structural integrity of the p53 RNA is critical
      for IRES function and is compromised by mutations that affect the structure as
      well as RNA protein interactions. In the current study, using RNA affinity
      approach we have identified Annexin A2 and PTB associated Splicing Factor
      (PSF/SFPQ) as novel ITAFs for p53 IRESs. We have showed that the purified Annexin
      A2 and PSF proteins specifically bind to p53 IRES elements. Interestingly, in the
      presence of calcium ions Annexin A2 showed increased binding with p53 IRES.
      Immunopulldown experiments suggest that these two proteins associate with p53
      mRNA ex vivo as well. Partial knockdown of Annexin A2 and PSF showed decrease in
      p53 IRES activity and reduced levels of both the p53 isoforms. More importantly
      the interplay between Annexin A2, PSF and PTB proteins for binding to p53mRNA
      appears to play a crucial role in IRES function. Taken together, our observations
      suggest pivotal role of two new trans-acting factors in regulating the p53-IRES
      function, which in turn influences the synthesis of p53 isoforms.

PMID- 23131773
TI  - Hydrogen bonding characteristics of 2-pyrrolidinone: a joint experimental and
      theoretical study.
AB  - The mid-IR spectrum of the hydrogen bonding lactam 2-pyrrolidinone in CCl(4) was
      studied using FT-IR spectroscopy accompanied by a quantum chemical anharmonic
      normal mode analysis combined with a Monte Carlo approach based on semi-empirical
      harmonic frequencies. We characterized and assigned the spectroscopic features in
      the range from 1500 cm(-1) to 3600 cm(-1) covering the respective amide bands
      related to hydrogen bonding CO and NH groups as well as the backbone CH
      vibrational band. By comparing theory and experiment we are able to assign all
      mid-IR features to a variety of distinct structures of 2-pyrrolidinone, ranging
      from monomers, singly and doubly hydrogen bonded dimers to longer hydrogen-bonded
      chains. These chains account for the most prominent features in the IR spectrum.
      Furthermore, two peaks in the CH band have been identified as highly localized
      axial and equatorial C-H stretch vibrations qualified for probes of
      conformational dynamics. The results provide a detailed microscopic picture of 2
      pyrrolidinone in solution, helpful for further dynamical structure studies of
      this amide.

PMID- 23131772
TI  - MicroRNA sequence profiles of human kidney allografts with or without
      tubulointerstitial fibrosis.
AB  - BACKGROUND: MicroRNA (miRNA) alterations accompanying interstitial fibrosis and
      tubular atrophy (IFTA) in kidney allografts may point toward pathologic
      mechanisms. Small-RNA sequencing provides information on total miRNA abundance
      and specific miRNA expression and allows analysis of differential expression
      based on read counts. METHODS: MiRNA expression profiles of 8 human kidney
      allograft biopsies (4 IFTA and 4 normal biopsies, discovery set) were
      characterized using barcoded deep-sequencing of a cDNA library prepared from
      multiplexed RNA. Statistical analysis of the sequence data guided selection of
      miRNAs for validation and the levels of selected miRNAs were quantified in 18
      biopsies (10 IFTA and 8 normal) using real-time quantitative PCR assays (RT
      QPCR). RESULTS: Total miRNA content was 50% lower in RNA from IFTA compared with
      normal biopsies. Global miRNA profiles clustered in partial agreement with
      diagnosis. Several miRNAs, including miR-21, 142-3p, and 5p and the cluster
      comprising miR-506 on chromosome X had twofold to sevenfold higher expression in
      IFTA compared with normal biopsies, whereas miRNA miR-30b and 30c were lower in
      IFTA biopsies (miR-30a, -30d, -30e, and all respective star sequences showed
      similar trends). IFTA and normal biopsy distinction was also noted in the pattern
      of miRNA nucleotide sequence variations. Differentially expressed miRNAs were
      confirmed on the larger set of allograft biopsies using RT-QPCR, and the levels
      of miRNAs were found to be associated with allograft function and survival.
      CONCLUSION: Differentially expressed miRNAs and their predicted targets
      identified by deep sequencing are candidates for further investigation to
      decipher the mechanism and management of kidney allograft fibrosis.

PMID- 23131774
TI  - On the discrepancy between theory and experiment for the F-F spin-spin coupling
      constant of difluoroethyne.
AB  - The vicinal indirect nuclear spin-spin coupling constant (SSCC) between the two
      fluorine atoms in difluoroethyne has been reinvestigated. This coupling has
      previously proved to be difficult to calculate accurately. In this study we have
      therefore systematically investigated the dependence of this coupling on the
      choice of one-electron basis set, the choice of correlated wave function method
      and the inclusion of zero-point vibrational and temperature corrections. All
      terms of the SSCC have been evaluated at the second-order polarization
      propagator, SOPPA and SOPPA(CCSD), and coupled cluster singles and doubles (CCSD)
      levels of theory and for the most correlation dependent term, the paramagnetic
      spin-orbit contribution (PSO), also at the very accurate CC3 level. We find that
      in order to get results that are well converged with respect to the basis set,
      one needs to use special SSCC optimized basis sets of at least quadruple zeta
      quality and with added diffuse functions. Furthermore, the PSO term is not yet
      converged at the CCSD level as shown by the CC3 calculations. Finally, it is
      shown that vibrational effects are very important, as they are in this case of
      the same order of magnitude as the equilibrium geometry value of the coupling
      constant. Only by using a converged basis set and including both vibrational and
      higher order correlation effects can we obtain agreement with the experimental
      value for this coupling.

PMID- 23131775
TI  - A preliminary experimental investigation of peer influence on risk-taking among
      adolescent smokers and non-smokers.
AB  - BACKGROUND: Epidemiological evidence suggests that peer influence plays a
      significant role in a variety of adolescent risk-taking behaviors, including
      tobacco use. We attempted to establish this relationship in a controlled
      laboratory setting. METHOD: We modified the Balloon Analog Risk Task (BART) task
      to include a peer component to investigate whether peer influences alter risk
      taking behaviors. Thirty-nine adolescents (22 smokers, 17 non-smokers) completed
      one experimental session during which the standard and peer BART were presented
      in counterbalanced order, with the dependent measures being adjusted mean number
      of pumps and explosions. We also examined the relationship of changes in the BART
      (standard-peer) to personality measures of impulsivity (BIS-11) and resistance to
      peer influence (RPI). RESULTS: A significant interaction of BART type and smoking
      status was present (p=.05); specifically smokers had a greater increase in the
      number of explosions by 2.27 (SD=3.12) compared to an increase of .29 (SD=2.87)
      by non-smokers. BIS-11 scores were related to peer-influenced BART changes: those
      who were more impulsive experienced greater changes in risk-taking, but no
      similar relationships were observed for the RPI. CONCLUSIONS: These results
      suggest that peer influences enhance risk-taking among adolescents, and that
      smokers may be more susceptible to these influences.

PMID- 23131777
TI  - Decision-making deficits are still present in heroin abusers after short- to long
      term abstinence.
AB  - BACKGROUND: Substance dependent individuals (SDIs) consistently show deficits in
      decision making with biased choices toward immediate rewards, even at the expense
      of future consequences. However, relatively little evidence has been reported
      concerning the population of drug abusers who are exclusively addicted to heroin.
      METHODS: The present study tested 124 male abstinent "pure" heroin (AH) abusers
      (divided into short-term, mid-term, and long-term groups based on their length of
      abstinence) and 43 healthy controls (HC) intending to address this issue. Two
      decision-making tasks, the Delay Discounting Task (DDT) and the Iowa Gambling
      Task (IGT) were employed to measure their decision-making performance. RESULTS:
      Compared to HC participants, AH participants made significantly poorer choices on
      both the DDT and the IGT and the poor decision-making performances were not
      influenced by their lengths of abstinence. It is suggested that heroin-abuse
      related decision-making deficits that are demonstrated by rapidly discounting
      future rewards; preferring incentives with large short-term gains while ignoring
      accompanying potential risks; and being inflexible in adjusting decision-making
      behaviors in accordance with outcome feedback, may not be compensated for even
      after a long period of abstinence from heroin abuse. CONCLUSION: Hence, this
      inability to recover should be taken into consideration in the evaluation,
      prevention and intervention of heroin abuse and relapse.

PMID- 23131776
TI  - Drug spend and acquisitive offending by substance misusers.
AB  - AIM: The need to generate income to fund drug misuse is assumed to be a driver of
      involvement in acquisitive crime. We examined the influence of drug misuse
      expenditure, and other factors, on acquisitive offending. METHODS: Clients
      (N=1380) seeking drug treatment within 94 of 149 Drug Action Teams (DATs) across
      England completed a comprehensive survey, incorporating validated scales and self
      report measures, such as levels of drug and alcohol use and offending. RESULTS:
      Forty per cent (N=554) had committed acquisitive crime in the previous month.
      Regression analysis showed that acquisitive offending was associated with the
      presence of problematic use of crack cocaine, poly-drug use, sharing injecting
      equipment, unsafe sex, overdose risk, higher drug spend, unemployment, reduced
      mental wellbeing, and younger age. CONCLUSIONS: Rates of acquisitive crime among
      drug users are high. Drug using offenders can be distinguished from drug using
      non-offenders by problematic crack cocaine use, younger age, income-related
      factors, and indicators of a chaotic life style and complex needs. Behavioural
      and demographic factors were associated more strongly with acquisitive crime than
      drug use expenditure, suggesting that the need to finance drug use is not
      necessarily the main factor driving acquisitive offending by drug users.

PMID- 23131778
TI  - Electrochemically synthesized molecularly imprinted polymer of thiophene
      derivatives for flow-injection analysis determination of adenosine-5'
      triphosphate (ATP).
AB  - Two selective chemosensors for adenosine-5'-triphosphate (ATP) determination
      featuring molecularly imprinted polymer (MIP) film recognition units were
      fabricated. For imprinting, three different thiophene derivatives were used as
      functional monomers. That is, the uracil substituent of bis(2,2'
      bithienyl)methane 2 complementarily H-bond paired the adenine moiety of ATP, the
      boronic acid substituent of thiophene 3 covalently bound vicinal diols of the
      ribofuranose moiety, and amide substituents of bis(2,2'-bithienyl)methanes 4
      bound to the pyrophosphate moieties. Different binding motifs adopted for the ATP
      recognition and the structure of the supramolecular pre-polymerization complex
      were optimized with the DFT computing at the B3LYP/3-21G((*)) level. MIP films
      were prepared by potentiodynamic electropolymerization of this complex with the
      imprinting factor of 9.47+/-0.2. An analytical signal was transduced with a 10
      MHz resonator of EQCM and a Pt electrode for the piezoelectric microgravimetry
      (PM) and capacitive impedometry (CI) determination of ATP, respectively, under
      FIA conditions. Analytical properties of the MIP film were unraveled by
      spectroscopic ellipsometry, XPS, IRRAS, and DPV. The limit of detection was 0.1
      and 0.2 MUM for the PM and CI chemosensor, respectively, being an order of
      magnitude lower than the ATP concentration in biological systems. Moreover, cross
      selectivity was demonstrated with the adenosine-5'-diphosphate (ADP) imprinting
      and ATP discrimination.

PMID- 23131780
TI  - Investigation of the roles of fascioliasis and food allergy in intrahepatic
      eosinophilic proliferative pylephlebitis in Japanese Black cattle.
AB  - Intrahepatic eosinophilic proliferative pylephlebitis (EPP) in Japanese Black
      (JB) cattle generally has been considered to be an atypical form of fascioliasis.
      However, there are many cases of EPP in which no Fasciola spp. have been detected
      in the livers of affected cattle. The aims of this study were to ascertain the
      relationship between EPP and hepatic fascioliasis and to investigate the role of
      food allergy in the disease. Histologically, EPP lesions were characterised by
      severe endothelial proliferation of the interlobular veins, accompanied by
      varying degrees of fibrosis and eosinophilic infiltration in portal areas, which
      could be differentiated from chronic cholangiohepatitis, the typical lesion of
      hepatic fascioliasis. In addition to hepatic lesions, all cases of EPP had
      varying degrees of eosinophilic infiltration in the perilymphoid red pulp of the
      spleen, whereas both affected and unaffected animals had eosinophilic infiltrates
      in the mucosa of the small intestine. Antibodies against Fasciola spp. were
      detected in 1/14 EPP cases by ELISA; the seropositive case had EPP in combination
      with chronic cholangitis. There was no significant difference in total
      concentration of IgE between cases of EPP and unaffected cattle. Serum IgE levels
      specific to curly dock (Rumex crispus) and oats (Avena sativa) were higher in EPP
      cases than in unaffected cattle by allergen profiling screening testing and
      ELISA. The results of this study suggest that hepatic fascioliasis is unlikely to
      be the cause of EPP in JB cattle and that food allergens should be investigated
      as possible aetiological agents.

PMID- 23131781
TI  - Reproductive hormone profiles in sows on estrus synchronization using estradiol
      dipropionate and prostaglandin F(2alpha)-analogue and the reproductive
      performance in female pigs on commercial farms.
AB  - Changes in ovarian structures and hormonal profiles in estradiol dipropionate
      (EDP)-induced pseudopregnant sows following PGF2alpha-analogue (PGF2alpha-A)
      administration and practicality of the estrus synchronization protocol using EDP
      and PGF2alpha-A on estrus expression and reproductive performance in commercial
      conditions were investigated. Pseudopregnancy was defined as absence of estrus
      maintained for at least 20 days after EDP treatment in this study. When 4
      pseudopregnant sows induced by 20 mg EDP were treated with PGF2alpha-A as 0.175
      mg cloprostenol twice at a 24-hr interval between 20 and 28 days after EDP
      treatment, plasma progesterone concentrations rapidly decreased after treatment.
      The luteinizing hormone surge and ovulation were detected in all sows. The number
      of ovulated follicles was 17.3 +/- 1.1 (SEM). On commercial farms, 94.2% of 52
      gilts and 95.2% of 21 sows received EDP became pseudopregnant. When these
      pseudopregnant females (48 gilts and 20 sows) were treated with PGF2alpha-A as
      described above, estrus was detected in all females at 6.1 +/- 0.3 days for gilts
      and 5.5 +/- 0.2 days for sows after the first PGF2alpha-A treatment. There were
      no significant differences in farrowing rate (85.0 - 100%), average total litter
      size (10.0 - 11.4), average born alive litter size (9.4 - 10.3) and average
      piglet birth weight (1.56 - 1.71 kg) between PGF2alpha-A treated pseudopregnant
      female pigs that were inseminated during synchronized estrus and females
      inseminated during spontaneous estrus. This study indicates that estrus
      synchronization programs using EDP and PGF2alpha-A are available as practical and
      convenient procedures for commercial pig farms.

PMID- 23131782
TI  - A potential therapeutic application of SET/I2PP2A inhibitor OP449 for canine T
      cell lymphoma.
AB  - Lymphoma is one of the most common malignant tumors in canine. Chemotherapy
      results in a high rate of remission; however, relapse and clinical drug
      resistance are usually seen within a year. Protein phosphatase 2A (PP2A) acts as
      a tumor suppressor and plays a critical role in mammalian cell transformation.
      Increased protein levels of SET, endogenous PP2A inhibitor, have been reported to
      correlate with poor prognosis in human leukemia. Here, we test the potential
      therapeutic role for a SET antagonist in canine lymphoma. We observed SET protein
      levels increased in multiple canine lymphoma cell lines compared with primary
      peripheral blood cells. A novel SET antagonist OP449 increased PP2A activity and
      effectively killed SET high-expressing canine lymphoma cells, but not SET low
      expressing cells. Caspase-3 activation and enhanced Annexin V positive staining
      were observed after OP449 treatment, suggesting apoptotic cell death by OP449.
      Consistent with this, pan-caspase inhibitor Z-VAD-FMK blocked OP449 induced cell
      death. These data demonstrated the potential therapeutic application of SET
      antagonists for canine lymphoma.

PMID- 23131783
TI  - Differentially imprinted innate immunity by mucosal boost vaccination determines
      antituberculosis immune protective outcomes, independent of T-cell immunity.
AB  - Homologous and heterologous parenteral prime-mucosal boost immunizations have
      shown great promise in combating mucosal infections such as tuberculosis and
      AIDS. However, their immune mechanisms remain poorly defined. In particular, it
      is still unclear whether T-cell and innate immunity may be independently affected
      by these immunization modalities and how it impacts immune protective outcome.
      Using two virus-based tuberculosis vaccines (adenovirus (Ad) and vesicular
      stomatitis virus (VSV) vectors), we found that while both homologous (Ad/Ad) and
      heterologous (Ad/VSV) respiratory mucosal boost immunizations elicited similar T
      cell responses in the lung, they led to drastically different immune protective
      outcomes. Compared with Ad-based boosting, VSV-based boosting resulted in poorly
      enhanced protection against tuberculosis. Such inferior protection was associated
      with differentially imprinted innate phagocytes, particularly the
      CD11c(+)CD11b(+/-) cells, in the lung. We identified heightened type 1 interferon
      (IFN) responses to be the triggering mechanism. Thus, increased IFN-beta severely
      blunted interleukin-12 responses in infected phagocytes, which in turn impaired
      their nitric oxide production and antimycobacterial activities. Our study reveals
      that vaccine vectors may differentially imprint innate cells at the mucosal site
      of immunization, which can impact immune-protective outcome, independent of T
      cell immunity, and it is of importance to determine both T-cell and innate cell
      immunity in vaccine studies.

PMID- 23131784
TI  - Functional diversity of human vaginal APC subsets in directing T-cell responses.
AB  - Human vaginal mucosa is the major entry site of sexually transmitted pathogens
      and thus has long been attractive as a site for mounting mucosal immunity. It is
      also known as a tolerogenic microenvironment. Here, we demonstrate that immune
      responses in the vagina can be orchestrated by the functional diversity of four
      major antigen-presenting cell (APC) subsets. Langerhans cells (LCs) and CD14(-)
      lamina propria-dendritic cells (LP-DCs) polarize CD4(+) and CD8(+) T cells toward
      T-helper type 2 (Th2), whereas CD14(+) LP-DCs and macrophages polarize CD4(+) T
      cells toward Th1. Both LCs and CD14(-) LP-DCs are potent inducers of Th22. Owing
      to their functional specialties and the different expression levels of pattern
      recognition receptors on the APC subsets, microbial products do not bias them to
      elicit common types of immune responses (Th1 or Th2). To evoke desired types of
      adaptive immune responses in the human vagina, antigens may need to be targeted
      to proper APC subsets with right adjuvants.

PMID- 23131786
TI  - Constitutive production of IL-13 promotes early-life Chlamydia respiratory
      infection and allergic airway disease.
AB  - Deleterious responses to pathogens during infancy may contribute to infection and
      associated asthma. Chlamydia respiratory infections in early life are common
      causes of pneumonia and lead to reduced lung function and asthma. We investigated
      the role of interleukin-13 (IL-13) in promoting early-life Chlamydia respiratory
      infection, infection-induced airway hyperresponsiveness (AHR), and severe
      allergic airway disease (AAD). Infected infant Il13(-/-) mice had reduced
      infection, inflammation, and mucus-secreting cell hyperplasia. Surprisingly,
      infection of wild-type (WT) mice did not increase IL-13 production but reduced IL
      13Ralpha2 decoy receptor levels compared with sham-inoculated controls. Infection
      of WT but not Il13(-/-) mice induced persistent AHR. Infection and associated
      pathology were restored in infected Il13(-/-) mice by reconstitution with IL-13.
      Stat6(-/-) mice were also largely protected. Neutralization of IL-13 during
      infection prevented subsequent infection-induced severe AAD. Thus, early-life
      Chlamydia respiratory infection reduces IL-13Ralpha2 production, which may
      enhance the effects of constitutive IL-13 and promote more severe infection,
      persistent AHR, and AAD.

PMID- 23131788
TI  - Syntheses, structure, and magnetic properties of heteronuclear Cu(II)4Fe(III)4
      cluster and Cu(II)8 bimetallacycles.
AB  - The compartmental Schiff base ligands N,N'-ethylenebis(3-hydroxysalicylidene)
      (H(4)L) and N,N'-propylenebis(3-hydroxysalicylidene) (H(4)L') have been employed
      in the synthesis of a cyclic tetranuclear Cu(II) complex
      [Cu(4)(L')(2)(MeOH)(3)(H(2)O)].[Cu(4)(L')(2)(MeOH)(3)] (1), a novel octanuclear
      Cu(II) complex [Cu(8)(L-L)(2)(H(2)O)(4)(MU(2)-H(2)O)].3DMF.3H(2)O (2) and a
      hetero-octanuclear Cu(II)-Fe(III) complex [Cu(4)Fe(4)(L)(4)(H(2)O)(3)(MU(3)
      O)(2)].3DMF.3H(2)O (3). During the formation of the Cu(8) complex (2), a new bis
      Schiff base ligand (L-L)(8-) forms via the ortho-para C-C coupling of two H(4)L
      ligands. The bicyclic complex (2) is comprised of two cyclic Cu(4) units that are
      similar to that of complex 1. In the Cu(4) unit, the alternate Cu(II) ions are
      singly bridged by phenoxo groups. The three complexes display overall
      antiferromagnetic coupling, and the Cu(II)-Cu(II) magnetic coupling constant
      falls in the range -117.2 to -473.6 cm(-1) for complexes 1 and 2 corresponding to
      the bridging Cu-O(phenoxide)-Cu bond angles of 124.3-131.0 degrees .

PMID- 23131789
TI  - Stochastic synchronization of interacting pathways in testosterone model.
AB  - We examine the possibilities of various coupling mechanisms among a group of
      identical stochastic oscillators via Chemical Langevin formalism where each
      oscillator is modeled by stochastic model of testosterone (T) releasing pathway.
      Our results show that the rate of synchrony among the coupled oscillators depends
      on various parameters namely fluctuating factor, coupling constants [symbol; see
      text], and interestingly on system size. The results show that synchronization is
      achieved much faster in classical deterministic system rather than stochastic
      system. Then we do large scale simulation of such coupled pathways using
      stochastic simulation algorithm and the detection of synchrony is measured by
      various order parameters such as synchronization manifolds, phase plots etc and
      found that the proper synchrony of the oscillators is maintained in different
      coupling mechanisms and support our theoretical claims. We also found that the
      coupling constant follows power law behavior with the systems size (V) by
      [symbol; see text] ~ AV(-gamma), where gamma=1 and A is a constant. We also
      examine the phase transition like behavior in all coupling mechanisms that we
      have considered for simulation. The behavior of the system is also investigated
      at thermodynamic limit; where V -> infinity, molecular population, N -> infinity
      but N/V -> finite, to see the role of noise in information processing and found
      the destructive role in the rate of synchronization.

PMID- 23131785
TI  - Guarding the perimeter: protection of the mucosa by tissue-resident memory T
      cells.
AB  - Mucosal tissues are continually bombarded with infectious agents seeking to gain
      entry into the body. The absence of a tough physical exterior layer surrounding
      these tissues creates a unique challenge for the immune system, which manages to
      provide broad protection against a plethora of different organisms with the aid
      of special adaptations that augment immunity at these vulnerable sites. For
      example, specialized populations of memory T lymphocytes reside at initial sites
      of pathogen entry into the body, where they provide an important protective
      barrier. Similar anatomically-confined populations of pathogen-specific CD8 T
      cells can be found near the outer margins of the body following recovery from a
      variety of local infections, where they share very similar phenotypic
      characteristics. How these tissue-resident T cells are retained in a single
      anatomic location where they can promote immunity is beginning to be defined.
      Here, we will review current knowledge of the mechanisms that help establish and
      maintain these regional lymphocytes in the mucosal tissues and discuss relevant
      data that enhance our understanding of the contribution of these lymphocyte
      populations to protective immunity against infectious diseases.

PMID- 23131790
TI  - Load-bearing in cortical bone microstructure: Selective stiffening and
      heterogeneous strain distribution at the lamellar level.
AB  - An improved understanding of bone mechanics is vital in the development of
      evaluation strategies for patients at risk of bone fracture. The current
      evaluation approach based on bone mineral density (BMD) measurements lacks
      sensitivity, and it has become clear that as well as bone mass, bone quality
      should also be evaluated. The latter includes, among other parameters, the bone
      matrix material properties, which in turn depend on the hierarchical structural
      features that make up bone as well as their composition. Optimal load transfer,
      energy dissipation and toughening mechanisms have, to some extent, been uncovered
      in bone. Yet, the origin of these properties and their dependence upon the
      hierarchical structure and composition of bone are largely unknown. Here we
      investigate load transfer in the osteonal and sub-osteonal levels and the
      mechanical behaviour of osteonal lamellae and interlamellar areas during loading.
      Using cantilever-based nanoindentation, in situ microtensile testing during
      atomic force microscopy (AFM) and digital image correlation (DIC), we report
      evidence for a previously unknown mechanism. This mechanism transfers load and
      movement in a manner analogous to the engineered "elastomeric bearing pads" used
      in large engineering structures. MU-RAMAN microscopy investigations showed
      compositional differences between lamellae and interlamellar areas. The latter
      have lower collagen content but an increased concentration of noncollagenous
      proteins (NCPs). Hence, NC-enriched areas on the microscale might be similarly
      important for bone failure as ones on the nanoscale. Finally, we managed to
      capture stable crack propagation within the interlamellar areas in a time-lapsed
      fashion, proving their significant contribution towards fracture toughness.

PMID- 23131791
TI  - Effects of gamma ray and electron beam irradiation on the mechanical, thermal,
      structural and physicochemical properties of poly (ether-block-amide)
      thermoplastic elastomers.
AB  - Both gamma ray and electron beam irradiation are widely used as a means of
      medical device sterilisation. However, it is known that the radiation produced by
      both processes can lead to undesirable changes within biomedical polymers. The
      main objective of this research was to conduct a comparative study on the two key
      radiosterilisation methods (gamma ray and electron beam) in order to identify the
      more detrimental process in terms of the mechanical, structural, chemical and
      thermal properties of a common biomedical grade polymer. Poly (ether-block-amide)
      (PEBA) was prepared by injection moulding ASTM testing specimens and these were
      exposed to an extensive range of irradiation doses (5-200 kGy) in an air
      atmosphere. The effect of varying the irradiation dose concentration on the
      resultant PEBA properties was apparent. For instance, the tensile strength,
      percentage elongation at break and shore D hardness can be increased/decreased by
      controlling the aforementioned criteria. In addition, it was observed that the
      stiffness of the material increased with incremental irradiation doses as
      anticipated. Melt flow index demonstrated a dramatic increase in the melting
      strength of the material indicating a sharp increase in molecular weight.
      Conversely, modulated differential scanning calorimetry established that there
      were no significant alterations to the thermal transitions. Noteworthy trends
      were observed for the dynamic frequency sweeps of the material, where the
      crosslink density increased according to an increase in electron beam irradiation
      dose. Trans-vinylene unsaturations and the carbonyl group concentration increased
      with an increment in irradiation dose for both processes when observed by FTIR.
      The relationship between the irradiation dose rate, mechanical properties and the
      subsequent surface properties of PEBA material is further elucidated throughout
      this paper. This study revealed that the gamma irradiation process produced more
      adverse effects in the PEBA material in contrast to the electron beam irradiation
      process.

PMID- 23131792
TI  - The lumbar supraspinous ligament demonstrates increased material stiffness and
      strength on its ventral aspect.
AB  - The present work represents the first reported quantified anisotropic,
      inhomogeneous material constitutive data for the human supraspinous ligament
      (SSL). Multi-axial material data from 30 human cadaveric SSL samples was
      collected from distinct locations (dorsal, midsection, and ventral). A
      structurally motivated strain-energy based continuum model was employed to
      characterize anisotropic constitutive parameters for each sample. The anisotropic
      constitutive response correlated well with the reported experimental data
      (R2>0.97). Results show that in the lumbar spine both the material stiffness and
      stress at failure were significantly higher in the ventral region of the SSL as
      compared with the dorsal region (p<0.05). In the along fiber direction a higher
      stiffness and stress at failure were observed when compared to the transverse
      direction. These results indicate that modeling spinal ligaments using the
      hyperelastic line elements that have typically been used may be insufficient to
      capture their complex material response.

PMID- 23131793
TI  - Phase-structure and mechanical properties of isothermally melt-and cold
      crystallized poly (L-lactide).
AB  - The effects of crystallinity differences induced by isothermal melt- and cold
      crystallizations on thermal, mechanical and morphological behavior of poly (L
      lactide) (PLLA) have been investigated. PLLA samples were crystallized from the
      melt and annealed from the glassy state at 80, 100 and 120  degrees C. The degree
      of crystallinity (Xc) and rigid amorphous phase (RAP) of PLLA was found to
      increase by crystallizing the samples at higher temperatures. Dynamic mechanical
      analysis (DMA) results suggest the presence of a rubber-like structure composed
      by both amorphous and crystalline phases for crystallized specimens. When samples
      are cold-crystallized, the structural integrity about Tg can be better kept,
      prompting to a smaller E' reduction after glass transition. Improvements in
      Young's modulus from 1027 MPa for quenched PLLA to 1401 MPa for the sample melt
      crystallized at 120  degrees C together with ductility reduction are obtained as
      the crystallization temperature increases. The tensile stress-strain curves at a
      range of temperatures, comprising below and above glass transition, have provided
      a mean for computing the mechanical properties ready for being used in linear
      elastic, visco-elastic and hyperelastic computing models. Polarized light optical
      microscopy (PLOM) and atomic force microscopy (AFM) analysis revealed completely
      different morphologies for melt-crystallized and cold-crystallized samples. When
      PLLA was crystallized from the melt surface roughness increases up to 566 nm,
      while the increase in spherulite diameter is accompanied by a monotonous decrease
      of the nucleation density. However, when PLLA was cold-crystallized the obtained
      semicrystalline structure is independent of the crystallization temperature
      because nucleation occurred upon quenching.

PMID- 23131794
TI  - Recurrent Langerhans cell histiocytosis of the mandible.
AB  - We report a case of Langerhans cell histiocytosis with a restricted presentation
      (eosinophilic granuloma of the mandible) complicated by multiple reactivations.

PMID- 23131795
TI  - A novel anchorage technique for transnasal traction in rigid external maxillary
      distraction.
AB  - We describe an effective technique for anchorage of transnasal traction in the
      management of maxillary rotation during external distraction. 

PMID- 23131796
TI  - Cell-surface glycosaminoglycans inhibit intranuclear uptake but promote post
      nuclear processes of polyamidoamine dendrimer-pDNA transfection.
AB  - BACKGROUND: Interaction of cell-surface glycosaminoglycans (GAGs) with non-viral
      vectors seems to be an important factor which modifies the intracellular
      destination of the gene complexes. Intracellular kinetics of polyamidoamine
      (PAMAM) dendrimer as a non-viral vector in cellular uptake, intranuclear delivery
      and transgene expression of plasmid DNA with regard to the cell-surface GAGs has
      not been investigated until now. METHODS: The physicochemical properties of the
      PAMAM-pDNA complexes were characterized by photon correlation spectroscopy,
      atomic force microscopy, zeta measurement and agarose gel electrophoresis. The
      transfection efficiency and toxicity of the complexes at different nitrogen to
      phosphate (N:P) ratios were determined using various in vitro cell models such as
      human embryonic kidney cells, chinese hamster ovary cells and its mutants lacking
      cell-surface GAGs or heparan sulphate proteoglycans (HSPGs). Cellular uptake,
      nuclear uptake and transfection efficiency of the complexes were determined using
      flow cytometry and optimized cell-nuclei isolation with quantitative real-time
      PCR and luciferase assay. RESULTS: Physicochemical studies showed that PAMAM
      dendrimer binds pDNA efficiently, forms small complexes with high positive zeta
      potential and transfects cells properly at N:P ratios around 5 and higher. The
      cytotoxicity could be a problem at N:Ps higher than 10. GAGs elimination caused
      nearly one order of magnitude higher pDNA nuclear uptake and more than 2.6-fold
      higher transfection efficiency than CHO parent cells. However, neither AUC of
      nuclear uptake, nor AUC of transfection affected significantly by only cell
      surface HSPGs elimination and interesting data related to the effect of GAGs on
      intranuclear pDNA using PAMAM as delivery vector have been reported in this
      study. CONCLUSION: Presented data shows that the rate-limiting step of PAMAM-pDNA
      complexes transfection is located after delivery to the cell nucleus and GAGs are
      regarded as an inhibitor of the intranuclear delivery step, while slightly
      promotes transgene expression.

PMID- 23131797
TI  - Large, chemically diverse dataset of logP measurements for benchmarking studies.
AB  - Lipophilicity is a crucial parameter in drug development since it impacts both
      ADME properties and target affinity of drug candidates. In early drug discovery
      stage, accurate tools for logP prediction are highly desired. Many calculation
      methods were developed to aid pharmaceutical scientists in drug research; however
      almost all suffer from insufficient accuracy and variation of performance in
      several regions of the chemical space associated with new chemical entities. The
      low predictive power of existing software packages can be explained by limited
      availability and/or variable quality of experimental logP values associated with
      training set used, which stem from various protocols and poorly cover chemical
      space. In this study, a dataset of 1000 diverse test compounds out of 4.5 million
      was generated; logP values of 759 purchasable compounds (46% non-ionizable, 30%
      basic, 17% acidic, 0.5% zwitterionic and 6.5% ampholytes) from this selected set
      were experimentally determined by UHPLC followed by UV detection or MS detection
      when necessary. Finally, a data collection of 707 validated logP values ranging
      from 0.30 to 7.50 is now available for benchmarking of existing and development
      of new approaches to predict octanol/water partition coefficients of chemical
      compounds.

PMID- 23131798
TI  - Discovery of novel cannabinoid receptor ligands by a virtual screening approach:
      further development of 2,4,6-trisubstituted 1,3,5-triazines as CB2 agonists.
AB  - 3D ligand-based virtual screening was employed to identify novel scaffolds for
      cannabinoid receptor ligand development. A total of 112 compounds with diverse
      structures were purchased from commercial vendors. 12 CB1 receptor
      antagonists/inverse agonists and 10 CB2 receptor agonists were identified in
      vitro. One of the CB2 agonists, N-cyclopentyl-4-ethoxy-6-(4-methylpiperidin-1-yl)
      1,3,5-triazin-2-amine (19, -logEC(50)=7.5, E(max)=255%) was selected for further
      development. As far as we are aware, the compound's 1,3,5-triazine scaffold
      represents a new core structure for CB2 agonists. A library of fifty-seven 2,4,6
      trisubstituted-1,3,5-triazines was created to clarify the structure-activity
      relationship study of the analogs.

PMID- 23131799
TI  - Solvent-free drug crystal engineering for drug nano- and micro suspensions.
AB  - Poor water-solubility is becoming the leading hurdle for novel drug molecules to
      reach the market. Enhancing the surface-to-volume ratio by reducing the drug
      particles size has emerged as a powerful method to enhance the drug dissolution
      rate of poorly water-soluble drugs. Here we present several approaches to produce
      micro- and nano-suspensions of febantel and itraconazole, as poorly water-soluble
      model drugs, in the presence of the self-emulsifying excipient Gelucire 44/14 as
      additional solubility enhancing agent. Two top-down approaches involving either
      ball milling or ultrasound treatment, to reduce the size of existing drug
      crystals, were used as reference processes. Both techniques allowed to
      significantly reduce the size of the drug crystals and enhance the dissolution of
      febantel with the ultrasound treated formulation performing the best. In case of
      itraconazole, no influence of both processing techniques was observed, which is
      likely to be attributed to it is extremely low water-solubility. To address this
      challenge, we developed a novel bottom up approach to produce nanosuspensions.
      This approach involved first dissolving the drug in molten Gelucire 44/14
      followed by atomization into cold water. During the atomization, cavitation was
      induced by ultrasonication. This process yielded milky suspensions in the
      submicrometer range. Furthermore a fraction of the drug was found to be in
      amorphous state. Nanosuspensions produced by this technique showed improved
      dissolution behavior, both in case of febantel and itraconazole.

PMID- 23131800
TI  - In vitro and in vivo evaluation of an in situ gel forming system for the delivery
      of PEGylated octreotide.
AB  - The objective of this study was to develop a controlled delivery system for
      PEGylated octreotide using a Poloxamer based in situ gel forming polymer.
      PEGylated octreotide kept its full biological activity and higher serum half-life
      compared to the original octreotide. The designed drug delivery system contained
      low concentration of Poloxamer 407 (P407) (<0.16%) with polyvinyl alcohol (PVA)
      as a polymeric additive. Rheological measurements of gel vehicle formulations
      indicated that the in situ gel forming system with optimum sol-gel transition
      temperature of 28.7 degrees C could be formed using a combination of P407 and PVA
      at ratio of 15-10% (w/v). The effect of formulation additives such as buffering
      agents on rheological behavior demonstrated that sodium bicarbonate and lactic
      acid have opposite effect on sol-gel transition temperature of the system. Using
      buffering agents, it was possible to shift the sol-gel transition to lower or
      higher temperatures. The in vitro release profiles of octreotide and PEGylated
      octreotide from the selected P407/PVA formulations were measured using a membrane
      less device. PEGylated octreotide showed slower release rate from the gel system
      with different release kinetic compared to octreotide. In animal studies, a
      sustained release rate was achieved with both PEGylated and non-PEGylated
      octreotide, but longer delivery was observed for PEGylated octreotide. Tissue
      histopathological studies confirmed the biocompatibility of the delivery system
      for PEGylated octreotide, supporting the suitability of P407/PVA mixture as an
      injectable drug delivery system. The total effects of increasing PEGylated
      peptide half-life and prolonged release from thermoresponsive gel system offer
      the potential for sustained delivery of PEGylated octreotide.

PMID- 23131801
TI  - Take-home "privileges" for methadone maintenance patients:  policies versus
      practices.

PMID- 23131804
TI  - Task difficulty manipulation reveals multiple demand activity but no frontal lobe
      hierarchy.
AB  - It has been proposed that task control is functionally implemented by a
      distributed frontoparietal system. It has been argued that one component of this
      system, the lateral frontal cortex, is functionally organized through a caudal to
      rostral gradient. Here, we tested 2 competing models, the Information Cascade and
      Rule Abstraction hypotheses, which suggest different principles underlying the
      rostrocaudal gradient. We presented participants with 4 vertical lines on a
      screen and asked them to indicate the position of the shortest line. We
      manipulated the difficulty of the task in 3 simple ways: By increasing the number
      of lines, by decreasing the difference between short and normal line length, and
      by changing the stimulus-response mapping. As expected, these manipulations
      evoked widespread frontoparietal activation, with activity much more anterior
      than predicted by Information Cascade and Rule Abstraction models. There were
      also striking individual differences in the rostrocaudal extent of activity. The
      results suggest an integrated frontoparietal system, which can be recruited as a
      whole even by very simple task demands.

PMID- 23131803
TI  - Developmental origin of patchy axonal connectivity in the neocortex: a
      computational model.
AB  - Injections of neural tracers into many mammalian neocortical areas reveal a
      common patchy motif of clustered axonal projections. We studied in simulation a
      mathematical model for neuronal development in order to investigate how this
      patchy connectivity could arise in layer II/III of the neocortex. In our model,
      individual neurons of this layer expressed the activator-inhibitor components of
      a Gierer-Meinhardt reaction-diffusion system. The resultant steady-state reaction
      diffusion pattern across the neuronal population was approximately hexagonal.
      Growth cones at the tips of extending axons used the various morphogens secreted
      by intrapatch neurons as guidance cues to direct their growth and invoke axonal
      arborization, so yielding a patchy distribution of arborization across the entire
      layer II/III. We found that adjustment of a single parameter yields the
      intriguing linear relationship between average patch diameter and interpatch
      spacing that has been observed experimentally over many cortical areas and
      species. We conclude that a simple Gierer-Meinhardt system expressed by the
      neurons of the developing neocortex is sufficient to explain the patterns of
      clustered connectivity observed experimentally.

PMID- 23131805
TI  - Neuroimaging evidence of the anatomo-functional organization of the human
      cingulate motor areas.
AB  - In the monkey, 3 motor areas have been identified in the cortex occupying the
      banks of the cingulate sulcus (cgs): A rostral cingulate motor area and 2 caudal
      cingulate motor areas, 1 located in the dorsal bank and the other in the ventral
      bank of the sulcus. The homologs of these 3 cingulate motor areas in the human
      brain are poorly understood. The present functional magnetic resonance imaging
      study examined the anatomo-functional organization of the cingulate motor areas
      in the human brain. A subject by subject analysis revealed the existence of 3
      motor areas along the cgs and these areas appear to be somatotopically organized.
      Importantly, these 3 motor areas relate to the specific morphological features of
      the cingulate/paracingulate cortex. These results demonstrate the location and
      organization of the 3 cingulate motor areas in the human brain and suggest a well
      preserved organization of these motor areas from the monkey to the human brain. 

PMID- 23131807
TI  - Education is better than splints in temperomandibular pain.

PMID- 23131808
TI  - Effect of cationic polyacrylamides on the aggregation and SERS performance of
      gold nanoparticles-treated paper.
AB  - This study examines and quantifies the effect of cationic polyelectrolyte
      adsorption on paper on the aggregation and retention of gold nanoparticles
      (AuNPs) to optimize their Surface Enhanced Raman Scattering (SERS) enhancement
      factor and sensitivity. Aggregation of metallic nanoparticles is known as a key
      factor for intense SERS enhancement. Paper substrates were treated with aqueous
      solutions of cationic polyacrylamide (CPAM) varying in concentration, charge
      density, and molecular weight to control the AuNPs' aggregate size distribution
      and surface coverage on paper. The Raman Enhancement Factor of AuNPs-CPAM paper
      was almost an order of magnitude greater than for the untreated AuNPs paper. The
      high loading and uniform distribution of AuNPs aggregates on CPAM pre-treated
      paper contributed toward the excellent SERS reproducibility, sensitivity, and
      high enhancement factor. This configuration of AuNP on paper was favoured by
      treating the substrate with CPAM solutions of higher concentrations, higher
      charge density, and greater molecular weight.

PMID- 23131809
TI  - Titanium dioxide nanospheres with wide spectral absorption prepared by low
      voltage plasma electrolysis.
AB  - TiO(2) nanospheres with diameters mostly in the range of 20-200 nm are prepared
      by using cathodic plasma electrolysis at low voltage of 70 V. It is found that
      the low voltage could efficiently depress the particle sizes and their
      distribution, and result in more anatase phases. The nanospheres have an
      excellent optical absorption from 240 nm to 2600 nm.

PMID- 23131806
TI  - Radial coherence of diffusion tractography in the cerebral white matter of the
      human fetus: neuroanatomic insights.
AB  - High angular resolution diffusion imaging (HARDI) demonstrates transient radial
      coherence of telencephalic white matter in the human fetus. Our objective was to
      define the neuroanatomic basis of this radial coherence through correlative HARDI
      and postmortem tissue analyses. Applying immunomarkers to radial glial fibers
      (RGFs), axons, and blood vessels in 18 cases (19 gestational weeks to 3 postnatal
      years), we compared their developmental profiles to HARDI tractography in brains
      of comparable ages (n = 11). At midgestation, radial coherence corresponded with
      the presence of RGFs. At 30-31 weeks, the transition from HARDI-defined radial
      coherence to corticocortical coherence began simultaneously with the
      transformation of RGFs to astrocytes. By term, both radial coherence and RGFs had
      disappeared. White matter axons were radial, tangential, and oblique over the
      second half of gestation, whereas penetrating blood vessels were consistently
      radial. Thus, radial coherence in the fetal white matter likely reflects a
      composite of RGFs, penetrating blood vessels, and radial axons of which its
      transient expression most closely matches that of RGFs. This study provides
      baseline information for interpreting radial coherence in tractography studies of
      the preterm brain in the assessment of the encephalopathy of prematurity. 

PMID- 23131810
TI  - Anodic formation of anatase TiO2 nanotubes with rod-formed walls for
      photocatalysis and field emitters.
AB  - Anatase TiO(2) nanotube arrays with rod-formed walls have been fabricated using a
      one-step anodic oxidation method for the first time. XRD, Raman spectroscopy,
      SEM, and HRTEM analysis were used for the structural characterization of the
      synthesized nanostructures. Their photocatalytic and field emission (FE)
      properties were also systematically investigated, and the experimental results
      indicated that the crystallization of the starting polycrystalline nanostructures
      turned into a better anatase phase after the annealed process. The photocatalytic
      properties showed that the nanostructures with optimized crystallization
      demonstrated faster degradation rate than the as-prepared polycrystalline
      counterparts, which would be caused by the improved crystallinity. Furthermore,
      the dependence of the FE properties on the distances between the anodes and the
      samples was investigated and the results revealed that the annealed samples have
      higher field enhancement factor beta compared to the as-prepared nanostructures.
      The formation mechanism of this novel rod-formed TiO(2) nanotubes is also briefly
      discussed.

PMID- 23131811
TI  - Lafora disease E3 ubiquitin ligase malin is recruited to the processing bodies
      and regulates the microRNA-mediated gene silencing process via the decapping
      enzyme Dcp1a.
AB  - Intracellular transport, processing and stability of mRNA play critical roles in
      the functional physiology of the cell and defects in these processes are thought
      to underlie the pathogenesis in a number of neurodegenerative disorders. One of
      the cellular sites that regulate the mRNA half-life is the processing bodies, the
      dynamic cytoplasmic structures that represent the non-translating mRNA and the
      ribonucleoprotein complex that also control the decapping and translation of
      mRNA. In the present study we explored the possible role of malin E3 ubiquitin
      ligase in the mRNA decay pathway via the processing bodies. Defects in malin are
      associated with Lafora disease (LD)-a neurodegenerative disorder characterized by
      myoclonus seizures. We show here that malin is recruited to the processing bodies
      and that malin regulates the recruitment of mRNA decapping enzyme Dcp1a by
      promoting its degradation via the ubiquitin proteasome system. Depletion of malin
      results in elevated levels of Dcp1a and an altered microRNA-mediated gene
      silencing activity. Our study suggests that malin is one of the critical
      regulators of processing bodies and that defects in the mRNA processing might
      underlie some of the disease symptoms in LD.

PMID- 23131812
TI  - Aims, design and methods of a case-control study for the assessment of the role
      of dietary habits, eating behaviors and environmental factors, on the development
      of breast cancer.
AB  - In this work the aims, methodology and procedures of a case-control study that
      was developed for assessing the role of dietary habits, eating behaviors and
      environmental factors on the development of breast cancer, is presented. During
      2010-2012, 250 consecutive women patients, newly diagnosed with breast cancer and
      250 population-based, healthy subjects (controls) age-matched to the cases, were
      enrolled. Socio-demographic, dietary, psychological, lifestyle as well as
      environmental characteristics (i.e., exposure to pollution, pesticides,
      electromagnetic fields and radon) were recorded through face-to-face interviews
      with the participants. Dietary habits and eating behaviors were evaluated with a
      special questionnaire that had been developed for the study, and was found
      relatively valid and reliable.

PMID- 23131813
TI  - Effect of green tea (Camellia sinensis) consumption on the components of
      metabolic syndrome in elderly.
AB  - OBJECTIVE: To evaluate the effect of the consumption of green tea on components
      of MS in the elderly. DESIGN: Intervention study. SETTING: The sample was
      selected from the Geriatric Service of Hospital Sao Lucas of Pontifical Catholic
      University of Rio Grande do Sul. PARTICIPANTS: 45 elderly with MS were enrolled
      and allocated into two groups: green tea group (GTG, n= 24), who drank green tea
      and control group (CG, n= 21) without intervention. INTERVENTION: The GTG
      received sachets of 1.0 g of green tea, and should drink three cups per day for
      60 days and the CG was instructed not to make changes in their lifestyle.
      MEASUREMENTS: The diagnostic criteria for MS used were the International Diabetes
      Federation. The lipidic and glycemic profile, and anthropometric measurements
      were evaluated before and after intervention. RESULTS: There was a statistically
      significant weight loss only in GTG [71.5+/-12.6 kg to 70.3+/-12.6 kg (p<0.001)].
      A statistically significant decrease in BMI [-0.5+/-0.4 kg/m2 in GTG and -0.2+/
      0.6 kg/m2 in CG (P=0.032)] and waist circumference [-2.2+/-2.0 cm in GTG and -
      0.3+/-1.8 cm in CG (P=0.002)] were observed. The intake of green tea did not
      change the biochemical parameters. CONCLUSION: The consumption of green tea was
      effective in inducing weight loss, reducing BMI and waist circumference in the
      elderly with MS.

PMID- 23131815
TI  - Life dissatisfaction and eating behaviors among older African Americans: the
      protective role of social support.
AB  - OBJECTIVES: To examine (a) the influences of life dissatisfaction and dietary
      social support on eating behaviors (a high-fat diet and fruit/vegetable
      consumption) of older African Americans and (b) the moderating role of perceived
      dietary social support on the association between their life dissatisfaction and
      unhealthy eating behaviors. DESIGN: Baseline data from a larger intervention
      study of mid-life and older African Americans. The study incorporated a quasi
      experimental design with random selection of participants, stratifying for age
      and gender. SETTING: Six churches in North Florida. PARTICIPANTS: One hundred and
      seventy-eight (132 females and 46 males with a median age of 60) older African
      Americans. MEASUREMENTS: A structured questionnaire elicited personal data as
      well as information on eating behaviors, life dissatisfaction, and perceived
      dietary social support. RESULTS: Older African Americans with more cumulative
      life adversity, as reflected by high life dissatisfaction, had significantly
      poorer eating behaviors including the consumption of a high-fat diet and low
      intake of fruits and vegetables. Older African Americans' dietary choices were
      also associated with their perceived social support. More importantly, perceived
      social support acted as a buffer to mitigate the influence of life
      dissatisfaction on older African Americans' eating behaviors. CONCLUSION: Life
      dissatisfaction places older African Americans at risk for unhealthy eating
      behaviors. However, high levels of dietary social support can protect older
      African Americans from the influence of life dissatisfaction on unhealthy eating
      behaviors. There are practical implications of this research for health
      interventions and programming.

PMID- 23131814
TI  - The protective effect of calcium on bone mass in postmenopausal women with high
      selenium intake.
AB  - OBJECTIVE: Nutritional factors, especially the two essential nutrients calcium
      and vitamin D, have been shown to play an important role in bone health. We
      wanted to determine the possible protective effect of calcium intake in adequate
      amounts on bone mass as assessed by quantitative ultrasound in postmenopausal
      women who also have a high intake of selenium. SETTING: Health district of
      Caceres, Spain. PARTICIPANTS AND STUDY DESIGN: 335 postmenopausal women aged 60.9
      (SD = 8.1) years. Women were stratified based on the vitamin D, vitamin E,
      calcium intake and the calcium/protein and calcium/phosphorous index.
      MEASUREMENTS: Bone status (Ad-SoS measured at the phalanges) was assessed with an
      ultrasound device model DBM Sonic 1200R. Food intake was quantified using
      dietetic scales, measuring cups, and spoons based on 7 days of diet records.
      Urine samples were collected the morning of testing after an overnight fast.
      Venous blood samples for the hematological and biochemical studies were also
      obtained in the fasting state. RESULTS: In the group of women with Ca intake <
      800 mg / d we found a significant and negative relationship between Ad-SoS with
      age (beta= -4.020, F = 23.327) and selenium intake (beta = -0.419, F = 10.067),
      as well as a positive relationship with Ca intake (beta= 0.104 and F = 7.084) (p
      <0.0001 in all). In the group of women with Ca intake > 800 mg / d, age has a
      significant and negative relationship (beta = -4.829 and F = 106.745), whereas
      folic acid intake has a significant and positive relationship (beta = 0.047 and F
      = 5.858) (p <0.0001 in both). CONCLUSION: Elevated selenium intake negatively
      affects bone mass measurements in postmenopausal women over the age of 51 but
      only if calcium intake is also less than 800 mg / day. When calcium intake is
      greater than 800 mg/day, selenium did not appear to affect bone mass.

PMID- 23131816
TI  - Tea drinking and cognitive function in oldest-old Chinese.
AB  - OBJECTIVE: We examined the longitudinal association between tea drinking
      frequency and cognitive function in a large sample of oldest-old Chinese. DESIGN:
      population-based longitudinal cohort study. SETTING: The Chinese Longitudinal
      Healthy Longevity Survey (CLHLS). PARTICIPANTS: 7139 participants aged 80 to 115
      (mean age 91.4 years) who provided complete data at baseline (year 1998).
      MEASUREMENTS: Current frequency of tea drinking and past frequency at age 60 were
      ascertained at baseline, and baseline and follow-up cognitive assessments were
      performed in the years 1998 (n=7139), 2000 (n=4081), 2002 (n=2288) and 2005
      (n=913) respectively. Verbal fluency test was used as measure of cognitive
      function. RESULTS: Tea drinking was associated at baseline with higher mean (SD)
      verbal fluency scores: daily=10.7 (6.6), occasional=9.2 (5.8), non-drinker=9.0
      (5.5). In linear mixed effects model that adjusted for age, gender, years of
      schooling, physical exercise and activities score, the regression coefficient for
      daily drinking (at age 60) and occasional drinking was 0.72 (P<0.0001) and
      0.41(P=0.01) respectively. Tea drinkers had higher verbal fluency scores
      throughout the follow-up period but concurrently had a steeper slope of cognitive
      decline as compared with non-drinkers (coefficient for the interaction term
      Time*Daily drinking= -0.12, P=0.02; "Time" was defined as the time interval from
      baseline to follow-up assessments in years). Similar results were found for
      current tea drinking status at study baseline year (1998) as predictor variable.
      CONCLUSION: Regular tea drinking is associated with better cognitive function in
      oldest-old Chinese.

PMID- 23131817
TI  - Feasibility and reliability of the Mini Nutritional Assessment (MNA) in older
      adults with intellectual disabilities.
AB  - OBJECTIVE: Feasibility and reliability of the Mini Nutritional Assessment (MNA)
      in older adults with intellectual disabilities (ID). DESIGN: Instrument
      development. SETTING: Three care providers for people with ID. PARTICIPANTS: 48
      persons aged 50 years and over with borderline to profound ID and their
      professional caregivers. MEASUREMENTS: The MNA was performed by means of
      interviews with participants (N = 12) and caregivers (N = 48) and physical
      assessments of participants (N = 47). Aspects of feasibility: completion of
      interview, difficulty of answering interview items, duration of interview and
      completion of physical assessment. Aspects of reliability: inter-observer
      reliability between caregivers and between participants and caregivers, test
      retest reliability and internal consistency. For inter-observer and test-retest
      reliability, intraclass correlation coefficients (ICC) were calculated, and for
      internal consistency Chronbach's alpha. RESULTS: All participants and caregivers
      completed the interview part. For 7 out of 12 personally interviewed participants
      and none of the caregivers, at least 3 out of 15 questions were difficult to
      answer. Mean duration of the interview was 7 minutes in participants and 4
      minutes in caregivers. Physical assessment was successfully performed in 40
      participants (85.1%). In the remaining 7 participants (14.9%) missing values were
      retrieved from the medical records. ICCs (95% confidence interval) for test
      retest and inter-observer reliability between caregivers were good, 0.85 (0.72 -
      0.92) and 0.86 (0.74 - 0.92) respectively, but ICC for inter-observer reliability
      between caregivers and persons with ID was low, 0.03 (-0.51 - 0.59). Internal
      consistency was 0.61. CONCLUSION: The MNA is feasible and reliable for older
      people with ID. Interview data can be reliably obtained through caregivers, but
      not through people with ID.

PMID- 23131818
TI  - Use of the Mini Nutritional Assessment to detect frailty in hospitalised older
      people.
AB  - OBJECTIVES: The aims of this study were to: (1) determine the prevalence of
      undernutrition and frailty in hospitalised elderly patients and (2) evaluate the
      efficacy of both the Mini-Nutritional Assessment (MNA) screening tool and the MNA
      short form (MNA-SF) in identifying frailty. SETTING AND PARTICIPANTS: A
      convenient sample of 100 consecutive patients (75.0 % female) admitted to the
      Geriatric Evaluation and Management Unit (GEMU) at The Queen Elizabeth Hospital
      in South Australia. MEASUREMENTS: Frailty status was determined using Fried's
      frailty criteria and nutritional status by the MNA and MNA-SF. Optimal cut-off
      scores to predict frailty were determined by Youden's Index, Receiver Operator
      Curves (ROC) and area under curve (AUC). RESULTS: Undernutrition was common.
      Using the MNA, 40.0% of patients were malnourished and 44.0% were at risk of
      malnutrition. By Fried's classification, 66.0 % were frail, 30.0 % were pre-frail
      and 4.0 % robust. The MNA had a specificity of 0.912 and a sensitivity of 0.516
      in predicting frailty using the recommended cut-off for malnourishment (< 17).
      The optimal MNA cut-off for frailty screening was <17.5 with a specificity of
      0.912 and sensitivity of 0.591. The MNA-SF predicted frailty with specificity and
      sensitivity values of 0.794 and 0.636 respectively, using the standard cut-off of
      < 8. The optimal MNA-SF cut-off score for frailty was < 9, with specificity and
      sensitivity values of 0.765 and 0.803 respectively and was better than the
      optimum MNA cut-off in predicting frailty (Youden Index 0.568 vs. 0.503).
      CONCLUSION: The quickly and easily administered MNA-SF appears to be a good tool
      for predicting both under-nutrition and frailty in elderly hospitalised people.
      Further studies would show whether the MNA-SF could also detect frailty in other
      populations of older people.

PMID- 23131819
TI  - Is grip strength a good marker of physical performance among community-dwelling
      older people?
AB  - INTRODUCTION: There is increasing interest in physical performance as it relates
      to both the current and future health of older people. It is often characterised
      using the Short Physical Performance Battery including assessment of gait speed,
      chair rises and standing balance. However this battery of tests may not be
      feasible in all clinical settings and simpler measures may be required. As muscle
      strength is central to physical performance, we explored whether grip strength
      could be used as a marker of the Short Physical Performance Battery. OBJECTIVE:
      To examine associations between grip strength and components of the Short
      Physical Performance Battery in older community dwelling men and women. METHODS:
      Grip strength measurement and the Short Physical Performance Battery were
      completed in 349 men and 280 women aged 63-73 years taking part in the
      Hertfordshire Cohort Study (HCS). Relationships between grip strength and
      physical performance (6m timed-up-and-go [TUG], 3m walk, chair rises and standing
      balance times) were analysed using linear and logistic regression, without and
      with adjustment for age, anthropometry, lifestyle factors and co-morbidities.
      RESULTS: Among men, a kilo increase in grip strength was associated with a 0.07s
      (second) decrease in 6m TUG, a 0.02s decrease in 3m walk time, and a 1% decrease
      in chair rises time (p<0.001 for all). Among women, a kilo increase in grip
      strength was associated with a 0.13s decrease in 6m TUG, a 0.03s decrease in 3m
      walk time, and a 1% decrease in chair rises time (p<0.001). Higher grip strength
      was associated with better balance among men (p=0.01) but not women (p=0.57).
      Adjustment for age, anthropometry, lifestyle and co-morbidities did not alter
      these results. CONCLUSIONS: Grip strength is a good marker of physical
      performance in this age group and may be more feasible than completing a short
      physical performance battery in some clinical settings.

PMID- 23131820
TI  - Physical function mitigates the adverse effects of being thin on mortality in a
      free-living older Taiwanese cohort.
AB  - OBJECTIVES: To examine the significance of underweight and physical function as
      well as their interaction on mortality in the aged. DESIGN: Prospective cohort.
      SETTING: The Elderly Nutrition and Health Survey in Taiwan during 1999-2000.
      PARTICIPANTS: Total of 1435 representative free-living elders (739 men and 696
      women). MEASUREMENTS: Body composition was assessed by various anthropometrics.
      Physical function score (PF, ranged 0-100) was derived from the SF-36((r)). Death
      by December 31, 2006 was the outcome measure. RESULTS: After 7.9 (median: 7.0)
      years follow-up, 381 (223 men, 158 women) of 1435 eligible participants had died.
      Those with the lowest PF (<45) had 3.43 (hazards ratio (HR), 95% confidence
      interval (CI) = 2.20-5.36) times the all-cause mortality risk of the highest PF
      (>=58). Interactions for PF and BMI (P =0.02) and for PF and wrist circumference
      (P =0.09) on death were found after controlling for potential confounders.
      Jointly, compared to normal-BMI-highest-PF, the greatest HR for death occurred
      where BMI <18.5 kg/m2 was combined with the lowest-PF after covariate adjustments
      (HR = 8.67, 95% CI = 3.77-20.0). Similarly, the lowest arm muscle circumference
      (MAMC)-PF had a HR of 5.22 compared to mid-MAMC-highest-PF. However, percent and
      absolute body fat, estimated by bioelectrical impedance, was comparable to non
      sarcopenic individuals. CONCLUSION: Thin elderly Taiwanese with sarcopenia, and
      less skeleton, are at the most risk of death, especially if physical function is
      limited.

PMID- 23131822
TI  - 5th conference clinical trials on Alzheimer's disease: October 29-31, 2012,
      Grimaldi Forum, Convention Center, Monte Carlo.

PMID- 23131821
TI  - Dietary protein and beef consumption predict for markers of muscle mass and
      nutrition status in older adults.
AB  - OBJECTIVE: To determine the relationship of beef and protein intake to nutrition
      status, body composition, strength, and biochemical measures of vitamin and
      mineral status, inflammation and blood lipids in older adults. DESIGN: Cross
      sectional observational study. SETTING: State of Ohio, U.S.A. PARTICIPANTS: 142
      adults ages 60-88. MEASUREMENTS: Subjects completed a Diet History Questionnaire,
      and questionnaires related to nutrition status and activity. Subjects also
      underwent measurements of body composition and strength, and a subset took part
      in a blood draw for biochemical measurements. RESULTS: Beef intake (g/d) was
      positively correlated to muscle mass measured by mid-arm muscle area (R=0.128,
      p=0.030). From multiple linear regression analysis, a 1oz/d (~28g/d) increase in
      beef consumption predicts for a 2.3cm(2) increase in mid-arm muscle area. Beef
      intake was negatively correlated to total (R=-0.179, p=0.035) and HDL (R=-0.247,
      p=0.004) cholesterol, and there was no association between beef and LDL
      cholesterol, triglycerides, liver enzymes, or inflammatory markers. Protein
      intake (% of total energy) was positively correlated to nutrition status measured
      by the Mini Nutrition Assessment (R=0.196, p=0.020), and calf circumference
      (R=0.190, p=0.024), and these correlations remained when potential confounders
      were accounted for in multiple linear regression models. Protein intake was also
      positively correlated with BMI when analyzed with multiple linear regression.
      CONCLUSIONS: Beef intake was positively associated with mid-arm muscle area, and
      protein intake was positively associated with nutrition status, calf
      circumference, and BMI in older adults. Consuming lean cuts of beef in moderation
      may be a healthy way in which older adults can increase protein intake, preserve
      muscle mass and improve nutrition status.

PMID- 23131824
TI  - Clinical diagnosis in preclinical stage of Alzheimer's disease.
AB  - Preclinical diagnosis of Alzheimer's disease using biomarkers has become an area
      of great interest for both clinicians and researchers because, among other
      advantages, this would increase the response to new disease-modifying drugs.
      However, difficulties with compliance and economic costs marginalize many
      countries worldwide that do not have access to this new type of diagnosis. The
      opportunity exists to refine the conventional clinical method, without using
      biomarkers, to attempt an earlier diagnosis as there is information that supports
      the potential utility of a focused clinical interview, observation of gait and
      use of more demanding memory tests.

PMID- 23131823
TI  - Can nutraceuticals prevent Alzheimer's disease? Potential therapeutic role of a
      formulation containing shilajit and complex B vitamins.
AB  - Alzheimer's disease (AD) is a brain disorder displaying a prevalence and impact
      in constant expansion. This expansive and epidemic behavior is concerning medical
      and public opinion while focusing efforts on its prevention and treatment. One
      important strategy to prevent this brain impairment is based on dietary changes
      and nutritional supplements, functional foods and nutraceuticals. In this review
      we discuss the potential contributions of shilajit and complex B vitamins to AD
      prevention. We analyze the status of biological studies and present data of a
      clinical trial developed in patients with mild AD. Studies suggest that shilajit
      and its active principle fulvic acid, as well as a formula of shilajit with B
      complex vitamins, emerge as novel nutraceutical with potential uses against this
      brain disorder.

PMID- 23131825
TI  - Oncologic and functional outcomes of partial laryngeal surgery for intermediate
      stage laryngeal cancer.
AB  - OBJECTIVE: To evaluate the oncologic and functional outcomes of partial laryngeal
      surgery (PLS) using transoral laser microsurgery (TLM) and supracricoid
      laryngectomy (SCL) in patients with intermediate-stage laryngeal squamous cell
      carcinoma (LSCC). STUDY DESIGN: Historical cohort study. SETTING: Single tertiary
      care center. SUBJECTS AND METHODS: Retrospective review of oncologic and
      functional outcomes in intermediate-stage (T2-3/N0-1, stage II and III) LSCC
      patients who underwent TLM or SCL from 1998 to 2010. RESULTS: Sixty patients were
      included, of whom 28 (47%) underwent TLM and 32 (53%) underwent SCL. For the
      entire cohort, 2- and 5-year probabilities were 86.2% (95% confidence interval
      [CI], 73.0%-93.2%) and 72.9% (95% CI, 52.4%-85.6%), respectively, for overall
      survival (OS) and 79.3% (95% CI, 65.6%-88.0%) and 62.4% (95% CI, 41.9%-77.4%),
      respectively, for recurrence-free survival (RFS). There was no difference between
      the TLM and SCL cohorts in OS (P = .542) or RFS (P = .483). More than 75% of
      patients avoided adjuvant therapy. Communication Scale and Functional Outcome
      Swallowing Scale scores at median follow-up of 33 months were 2 or better in 97%
      and 91% of patients, respectively, reflecting functional voice and swallowing
      postoperatively. Eighty-eight percent of patients retained a functional larynx.
      CONCLUSION: PLS provides excellent oncologic and functional outcomes for
      intermediate-stage LSCC and should be considered an alternative to chemoradiation
      or total laryngectomy in selected patients.

PMID- 23131826
TI  - Antimicrobial and analgesic prescribing patterns for acute otitis externa, 2004
      2010.
AB  - OBJECTIVE: Acute otitis externa (AOE) is a common but preventable ear condition.
      Clinical guidelines issued in 2006 recommended topical treatments for
      uncomplicated AOE, but systemic antimicrobials appear to be commonly prescribed.
      The objective of this analysis was to describe pre- and postguideline prescribing
      patterns by clinician specialty and antimicrobial type and assess trends over
      time. STUDY DESIGN: Retrospective longitudinal analysis of a large insurance
      database. SETTING: Outpatient departments in the United States. METHODS: Initial
      outpatient visits in 2004 to 2010 for AOE (excluding visits with complicating
      conditions) were extracted from an insurance database. Prescription drug claims
      were linked and categorized by clinician specialty and antimicrobial type.
      RESULTS: The analysis included 907,261 initial outpatient visits. Use of systemic
      antimicrobials declined by 4.9% (95% confidence interval [CI], 4.1%, 5.7%) from
      36.5% of initial visits in 2004 to 32.1% in 2010. Use of systemic antimicrobials
      varied by specialty. Systemic antimicrobials were prescribed in 47.1% of 2010
      emergency department (ED) visits (-6.9% from 2004, 95% CI -12.3, -1.5), 25.9% of
      otolaryngologist visits (-1.6%, 95% CI -5.6, 2.4), and 20.4% of pediatrician
      visits (-6.6%, 95% CI -8.8, -4.4). Penicillins were prescribed most frequently
      (42.3% of systemic prescriptions in 2010), followed by cephalosporins (19.8%),
      erythromycin/macrolides (17.4%), and quinolones (11.1%). Opioids were prescribed
      in 26.4% of ED visits and 9% of outpatient visits. CONCLUSIONS: Use of systemic
      antimicrobials declined over time, but one-third of 2010 visits resulted in
      systemic antimicrobials, despite exclusion of visits with complicating factors.
      Use of systemic antimicrobials varied by specialty. Further educational efforts
      and outreach to other specialties might be warranted.

PMID- 23131827
TI  - A new ab initio potential energy surface for the collisional excitation of O2 by
      H2.
AB  - We present a new four dimensional (4D) potential energy surface for the O(2)-H(2)
      system. Both molecules were treated as rigid rotors. Potential was obtained from
      the electronic structure calculations using a partially spin-restricted coupled
      cluster with the single, double and perturbative triple excitations [RCCSD(T)]
      method. The four atoms were described using the augmented correlation-consistent
      quadruple zeta (aug-cc-pVQZ) basis sets. Bond functions were placed at mid
      distance between the O(2) center of mass and the center of mass of H(2) for a
      better description of the van der Waals interaction. Additionally, at five
      characteristic geometries, we calculated perturbational components of the
      interaction energy using the Symmetry-Adapted Perturbation Theory [SAPT] approach
      to explain the anisotropy of the potential energy surface. Bound states of the
      O(2)-H(2) van der Waals complex are computed using this potential. Close coupling
      calculations of the inelastic integral cross sections of O(2) in collisions with
      para-H(2) and ortho-H(2) were also calculated at low energies. After Boltzmann
      thermal averaging, rate coefficients were obtained for temperatures ranging from
      5 to 100 K. No significant differences exist between para- and ortho-H(2)
      results.

PMID- 23131828
TI  - Glucose-specific enzyme IIA has unique binding partners in the vibrio cholerae
      biofilm.
AB  - Glucose-specific enzyme IIA (EIIA(Glc)) is a central regulator of bacterial
      metabolism and an intermediate in the phosphoenolpyruvate phosphotransferase
      system (PTS), a conserved phosphotransfer cascade that controls carbohydrate
      transport. We previously reported that EIIA(Glc) activates transcription of the
      genes required for Vibrio cholerae biofilm formation. While EIIA(Glc) modulates
      the function of many proteins through a direct interaction, none of the known
      regulatory binding partners of EIIA(Glc) activates biofilm formation. Therefore,
      we used tandem affinity purification (TAP) to compare binding partners of
      EIIA(Glc) in both planktonic and biofilm cells. A surprising number of novel
      EIIA(Glc) binding partners were identified predominantly under one condition or
      the other. Studies of planktonic cells revealed established partners of
      EIIA(Glc), such as adenylate cyclase and glycerol kinase. In biofilms, MshH, a
      homolog of Escherichia coli CsrD, was found to be a dominant binding partner of
      EIIA(Glc). Further studies revealed that MshH inhibits biofilm formation. This
      function was independent of the Carbon storage regulator (Csr) pathway and
      dependent on EIIA(Glc). To explore the existence of multiprotein complexes
      centered on EIIA(Glc), we also affinity purified the binding partners of
      adenylate cyclase from biofilm cells. In addition to EIIA(Glc), this analysis
      yielded many of the same proteins that copurified with EIIA(Glc). We hypothesize
      that EIIA(Glc) serves as a hub for multiprotein complexes and furthermore that
      these complexes may provide a mechanism for competitive and cooperative
      interactions between binding partners. IMPORTANCE: EIIA(Glc) is a global
      regulator of microbial physiology that acts through direct interactions with
      other proteins. This work represents the first demonstration that the protein
      partners of EIIA(Glc) are distinct in the microbial biofilm. Furthermore, it
      provides the first evidence that EIIA(Glc) may exist in multiprotein complexes
      with its partners, setting the stage for an investigation of how the multiple
      partners of EIIA(Glc) influence one another. Last, it provides a connection
      between the phosphoenolpyruvate phosphotransferase (PTS) and Csr (Carbon storage
      regulator) regulatory systems. This work increases our understanding of the
      complexity of regulation by EIIA(Glc) and provides a link between the PTS and Csr
      networks, two global regulatory cascades that influence microbial physiology.

PMID- 23131829
TI  - Comparative genomics of early-diverging Brucella strains reveals a novel
      lipopolysaccharide biosynthesis pathway.
AB  - Brucella species are Gram-negative bacteria that infect mammals. Recently, two
      unusual strains (Brucella inopinata BO1T and B. inopinata-like BO2) have been
      isolated from human patients, and their similarity to some atypical brucellae
      isolated from Australian native rodent species was noted. Here we present a
      phylogenomic analysis of the draft genome sequences of BO1T and BO2 and of the
      Australian rodent strains 83-13 and NF2653 that shows that they form two groups
      well separated from the other sequenced Brucella spp. Several important
      differences were noted. Both BO1T and BO2 did not agglutinate significantly when
      live or inactivated cells were exposed to monospecific A and M antisera against O
      side chain sugars composed of N-formyl-perosamine. While BO1T maintained the
      genes required to synthesize a typical Brucella O-antigen, BO2 lacked many of
      these genes but still produced a smooth LPS (lipopolysaccharide). Most missing
      genes were found in the wbk region involved in O-antigen synthesis in classic
      smooth Brucella spp. In their place, BO2 carries four genes that other bacteria
      use for making a rhamnose-based O-antigen. Electrophoretic, immunoblot, and
      chemical analyses showed that BO2 carries an antigenically different O-antigen
      made of repeating hexose-rich oligosaccharide units that made the LPS water
      soluble, which contrasts with the homopolymeric O-antigen of other smooth
      brucellae that have a phenol-soluble LPS. The results demonstrate the existence
      of a group of early-diverging brucellae with traits that depart significantly
      from those of the Brucella species described thus far. IMPORTANCE: This report
      examines differences between genomes from four new Brucella strains and those
      from the classic Brucella spp. Our results show that the four new strains are
      outliers with respect to the previously known Brucella strains and yet are part
      of the genus, forming two new clades. The analysis revealed important information
      about the evolution and survival mechanisms of Brucella species, helping reshape
      our knowledge of this important zoonotic pathogen. One discovery of special
      importance is that one of the strains, BO2, produces an O-antigen distinct from
      any that has been seen in any other Brucella isolates to date.

PMID- 23131830
TI  - Exploring the parallel development of microbial systems in neonates with cystic
      fibrosis.
AB  - Recent studies have greatly extended our understanding of the microbiota present
      in and on the human body. Here, advanced sequencing strategies have provided
      unprecedented analytical power. The important implications that the emerging data
      have for human health emphasize the need to intensify research in this area (D.
      A. Relman, Nature 486:194-195, 2012). It is already clear from these studies that
      the microbiotas characterized in different body locations of healthy individuals
      are both complex and diverse (The Human Microbiome Project Consortium, Nature
      486:215-221). These studies also provide a point of contrast for investigations
      that aim to characterize the microbiota present in disease conditions. In this
      regard, Madan et al. (mBio 3(4):e00251-12, 2012) monitored the development over
      time of microbiota in the oropharynges and feces of neonates with cystic fibrosis
      and explored the potential for interactions between these complex microbial
      systems.

PMID- 23131831
TI  - Novel Phosphorylations of IKKgamma/NEMO.
AB  - Central to NF-kappaB signaling pathways is IKKgamma/NEMO, a regulatory subunit of
      the cytoplasmic IkappaB kinase (IKK) complex, which undergoes various
      posttranslational modifications, specifically phosphorylation, to regulate its
      function. Furthermore, Kaposi's sarcoma-associated herpesvirus (KSHV) FADD-like
      interleukin-1beta (IL-1beta) converting enzyme (FLICE) inhibitory protein (vFLIP)
      activates the NF-kappaB signaling pathway by directly interacting with
      IKKgamma/NEMO. However, the exact functions of IKKgamma/NEMO phosphorylation and
      its KvFLIP interaction in NF-kappaB activation remain elusive. Here, we report
      two novel phosphorylation sites of IKKgamma/NEMO and their negative effect on the
      IKKgamma/NEMO-mediated NF-kappaB signaling pathway. First, the Src family protein
      tyrosine kinases (SF-PTKs), including Src, Fyn, Lyn, and Fgr, interact with and
      phosphorylate tyrosine residue 374 (Y374) of IKKgamma/NEMO. Mutation of the Y374
      residue to phenylalanine (Y374F) specifically abolished SF-PTK-mediated tyrosine
      phosphorylation, leading to increased tumor necrosis factor alpha (TNF-alpha)
      induced NF-kappaB activity. Moreover, our mass spectrometry analysis found that
      the serine 377 residue (S377) of IKKgamma/NEMO underwent robust phosphorylation
      upon KvFLIP expression. Replacement of the IKKgamma/NEMO S377 residue by alanine
      (S377A) or glutamic acid (S377E) resulted in a significant increase or decrease
      of NF-kappaB activity and TNF-alpha-mediated IL-6 cytokine production,
      respectively. Our study thus demonstrates that the Y374 or S377 residue located
      at the C-terminal proline-rich domain of human IKKgamma/NEMO undergoes
      phosphorylation upon TNF-alpha treatment or KvFLIP expression, respectively,
      resulting in the suppression of IKKgamma/NEMO activity to induce NF-kappaB
      activation. This study suggests the potential phosphorylation-mediated feedback
      negative regulation of IKKgamma/NEMO activity in the NF-kappaB signaling pathway.
      IMPORTANCE Since unchecked regulation of NF-kappaB has been linked to
      uncontrolled proliferation and cell death, the downregulation of the NF-kappaB
      signaling pathway is as important as its activation. Specifically, the
      phosphorylation-mediated modification of IKKgamma/NEMO is a critical regulatory
      mechanism of NF-kappaB activity. Here, we report two novel phosphorylations of
      IKKgamma/NEMO and their negative effects on the NF-kappaB signaling pathway.
      First, the Src family protein tyrosine kinase interacts with and phosphorylates
      tyrosine residue 374 of IKKgamma/NEMO, suppressing tumor necrosis factor alpha
      (TNF-alpha)-induced NF-kappaB activity. Additionally, Kaposi's sarcoma-associated
      herpesvirus (KSHV) FADD-like interleukin-1beta (IL-1beta) converting enzyme
      (FLICE) inhibitory protein (KvFLIP) expression induces a robust phosphorylation
      of the serine 377 residue of IKKgamma/NEMO, resulting in a significant decrease
      of NF-kappaB activity. Our study thus demonstrates that the Y374 or S377 residue
      of IKKgamma/NEMO undergoes phosphorylation upon TNF-alpha treatment or KvFLIP
      expression, respectively, resulting in the suppression of IKKgamma/NEMO activity
      to induce NF-kappaB activation. This also suggests the potential phosphorylation
      mediated feedback negative regulation of IKKgamma/NEMO activity in the NF-kappaB
      signaling pathway.

PMID- 23131832
TI  - Human disease isolates of serotype m4 and m22 group a streptococcus lack genes
      required for hyaluronic acid capsule biosynthesis.
AB  - Group A streptococcus (GAS) causes human pharyngitis and invasive infections and
      frequently colonizes individuals asymptomatically. Many lines of evidence
      generated over decades have shown that the hyaluronic acid capsule is a major
      virulence factor contributing to these infections. While conducting a whole
      genome analysis of the in vivo molecular genetic changes that occur in GAS during
      longitudinal human pharyngeal interaction, we discovered that serotypes M4 and
      M22 GAS strains lack the hasABC genes necessary for hyaluronic acid capsule
      biosynthesis. Using targeted PCR, we found that all 491 temporally and
      geographically diverse disease isolates of these two serotypes studied lack the
      hasABC genes. Consistent with the lack of capsule synthesis genes, none of the
      strains produced detectable hyaluronic acid. Despite the lack of a hyaluronic
      acid capsule, all strains tested multiplied extensively ex vivo in human blood.
      Thus, counter to the prevailing concept in GAS pathogenesis research, strains of
      these two serotypes do not require hyaluronic acid to colonize the upper
      respiratory tract or cause abundant mucosal or invasive human infections. We
      speculate that serotype M4 and M22 GAS have alternative, compensatory mechanisms
      that promote virulence. IMPORTANCE: A century of study of the antiphagocytic
      hyaluronic acid capsule made by group A streptococcus has led to the concept that
      it is a major virulence factor contributing to human pharyngeal and invasive
      infections. However, the discovery that some strains that cause abundant human
      infections lack hyaluronic acid biosynthetic genes and fail to produce this
      capsule provides a new stimulus for research designed to understand the group A
      streptococcus factors contributing to pharyngeal infection and invasive disease
      episodes.

PMID- 23131834
TI  - Effect of thymoquinone on 1,2-dimethyl-hydrazine-induced oxidative stress during
      initiation and promotion of colon carcinogenesis.
AB  - We evaluated pre- and post-thymoquinone (TQ) treatment on 1,2-dimethyl-hydrazine
      (DMH)-induced oxidative stress during initiation and promotion of colon
      carcinogenesis. Wistar rats were induced with DMH (20mg/kg) for 10 or 20 weeks,
      and treated with TQ (5mg/kg). Following sacrifice, the colons were analysed for
      tumour development, reactive oxygen species (ROS) generation, lipid peroxidation
      [conjugated diene (CD) and malondialdehyde (MDA)], antioxidants [glutathione
      peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD) and reduced
      glutathione (GSH)], and histological changes. Increased ROS levels and lipid
      peroxidation were seen during tumour initiation and promotion. All ROS-scavenging
      enzyme activities were increased upon shorter DMH treatment but not following
      longer treatment, while GSH amount was increased upon both treatments. Oxidative
      state perturbations were associated with moderate colon dysplasia and 30% tumour
      incidence at initiation and marked dysplasia and 100% tumour incidence at
      promotion. TQ pre-treatment restored completely DMH-induced oxidative stress at
      initiation and established histological changes and tumour development. It also
      abrogated oxidative status aggravation at promotion, and significantly reduced
      tumour incidence (67%). By comparison, TQ post-treatment corrected oxidative
      status and attenuated tumour development at initiation. It slightly reduced MDA
      and antioxidant level at promotion, with a slight reduction in tumour state and
      dysplasia degree. TQ is efficacious in protecting and curing DMH-induced
      initiation phase of colon cancer, while exerting a protective role at promotion.
      TQ effect seems to be related to its capacity in preventing DMH-induced oxidative
      stress. These in vivo results support the notion that TQ may be of value as a
      chemo-preventive alternative in colorectal cancer patients.

PMID- 23131833
TI  - Picornavirus modification of a host mRNA decay protein.
AB  - Due to the limited coding capacity of picornavirus genomic RNAs, host RNA binding
      proteins play essential roles during viral translation and RNA replication. Here
      we describe experiments suggesting that AUF1, a host RNA binding protein involved
      in mRNA decay, plays a role in the infectious cycle of picornaviruses such as
      poliovirus and human rhinovirus. We observed cleavage of AUF1 during poliovirus
      or human rhinovirus infection, as well as interaction of this protein with the 5'
      noncoding regions of these viral genomes. Additionally, the picornavirus
      proteinase 3CD, encoded by poliovirus or human rhinovirus genomic RNAs, was shown
      to cleave all four isoforms of recombinant AUF1 at a specific N-terminal site in
      vitro. Finally, endogenous AUF1 was found to relocalize from the nucleus to the
      cytoplasm in poliovirus-infected HeLa cells to sites adjacent to (but distinct
      from) putative viral RNA replication complexes. IMPORTANCE: This study derives
      its significance from reporting how picornaviruses like poliovirus and human
      rhinovirus proteolytically cleave a key player (AUF1) in host mRNA decay pathways
      during viral infection. Beyond cleavage of AUF1 by the major viral proteinase
      encoded in picornavirus genomes, infection by poliovirus results in the
      relocalization of this host cell RNA binding protein from the nucleus to the
      cytoplasm. The alteration of both the physical state of AUF1 and its cellular
      location illuminates how small RNA viruses manipulate the activities of host cell
      RNA binding proteins to ensure a faithful intracellular replication cycle.

PMID- 23131835
TI  - Recurrent targets of aberrant somatic hypermutation in lymphoma.
AB  - Somatic hypermutation (SHM) in the variable region of immunoglobulin genes (IGV)
      naturally occurs in a narrow window of B cell development to provide high
      affinity antibodies. However, SHM can also aberrantly target proto-oncogenes and
      cause genome instability. The role of aberrant SHM (aSHM) has been widely studied
      in various non-Hodgkin's lymphoma particularly in diffuse large B-cell lymphoma
      (DLBCL). Although, it has been speculated that aSHM targets a wide range of
      genome loci so far only twelve genes have been identified as targets of aSHM
      through the targeted sequencing of selected genes. A genome-wide study aiming at
      identifying a comprehensive set of aSHM targets recurrently occurring in DLBCL
      has not been previously undertaken. Here, we present a comprehensive assessment
      of the somatic hypermutated genes in DLBCL identified through an analysis of
      genomic and transcriptome data derived from 40 DLBCL patients. Our analysis
      verifies that there are indeed many genes that are recurrently affected by aSHM.
      In particular, we have identified 32 novel targets that show same or higher level
      of aSHM activity than genes previously reported. Amongst these novel targets, 22
      genes showed a significant correlation between mRNA abundance and aSHM.

PMID- 23131836
TI  - Video-assisted swallowing therapy for patients with Parkinson's disease.
AB  - BACKGROUND: Conventional swallowing therapy for patients with Parkinson's disease
      (PD) and swallowing difficulties has poor carryover to everyday life. Herein, we
      test the effectiveness of visual information while treating swallowing
      disturbances in patients with PD. METHODS: Forty two non-demented PD patients
      with swallowing disturbances were randomly divided into two groups. An
      experimental group received video-assisted swallowing therapy (VAST) and a
      control group (n = 21) was given conventional therapy. Both groups were given 6
      interventional sessions by the same speech and swallowing therapist. Patients in
      the VAST group were exposed to video of the swallowing process in general as well
      as of their own, as part of all therapy sessions. Swallowing function was
      assessed before and post-intervention by fiberoptic endoscopic evaluation of
      swallowing (FEES). Quality of life, quality of care and the degree of pleasure
      from eating were also assessed by questioners pre and post-intervention. RESULTS:
      There was a significant improvement in swallowing functions following both
      interventions. The FEESs demonstrated a significantly greater reduction in food
      residues in the pharynx in the VAST group compared to the conventional treatment
      group. There were significant group improvement in some parameters of the quality
      of life, quality of care and pleasure of eating scales. CONCLUSION: In
      cognitively intact patients with PD with swallowing disturbances VAST was
      associated with improved swallowing related QOL and less food residues in the
      pharynx.

PMID- 23131837
TI  - Synthesis, structure, magnetic properties and theoretical calculations of methoxy
      bridged dinuclear iron(III) complex with hydrazone based O,N,N-donor ligand.
AB  - Biomimetic complexes are artificially engineered molecules that aim to reduce the
      structural complexity of biological systems in order to unveil the key electronic
      and structural factors relevant to a protein's function. In this work, a novel
      coordination compound (L2Fe2) which mimics non-heme binuclear proteins was
      synthesized from the Schiff-base ligand HL = (E)-N'-(phenyl(pyridin-2
      yl)methylene)isonicotinohydrazide. The crystal structure of L2Fe2 showed that the
      intramolecular Fe-Fe distances (3.1-3.2 A) were analogous to those found in non
      heme binuclear ferric proteins. However, in L2Fe2, two methoxide groups act as
      bridging units for oxidized iron (Fe3+). Such a bridging motif is unprecedented
      in the biological realm. Magnetic susceptibility measurements demonstrated that
      L2Fe2 is characterized by a singlet (S = 0) ground state and a very small
      magnetic coupling constant J (? -1 cm(-1)). The J value featured by L2Fe2 differs
      considerably from the values observed in non-heme binuclear proteins in the
      oxidized form (-100 cm(-1) < J < -10 cm(-1)), which encompass oxo/hydroxo and
      carboxylate bridging residues. The singlet ground state of L2Fe2 as well as the
      weak magnetic interaction between the two ferric cations was successfully
      predicted by density functional theory (DFT).

PMID- 23131838
TI  - Prevalence of substance use and psychiatric disorders in a highly select chronic
      pain population.
AB  - OBJECTIVE: To estimate the prevalence of self-reported substance use and
      psychiatric disorders in a highly select chronic nonmalignant pain population
      within a nonprimary care tertiary referral-only pain clinic. METHODS: A
      retrospective, cross-sectional study was accomplished via existing medical record
      review for 216 consecutive pain patients presenting to an independent
      neurodiagnostic clinic located in the southeastern United States, specializing in
      chronic, severe, and complex industrial injuries (e.g., multiple failed fusions,
      neuropathic pain), involving complex combinations of nocioceptive, neuropathic,
      and myofascial pain. De-identified self-report data from the Comprehensive
      Assessment and Psychological Evaluation (a structured diagnostic assessment
      interview compatible with DSM-IV-TR criteria, which assesses for symptoms of 8
      Axis I and 6 Axis II disorders including substance-specific dependence and abuse)
      were obtained as part of the standard intake procedures for diagnostic
      determinations. Diagnostic assessment of substance use disorders was also
      independently verified by a physician certified by the American Society of
      Addiction Medicine. RESULTS: An extremely low prevalence of substance abuse and
      dependence diagnoses were found for 1.9% of the population, of which nearly 30%
      were not currently prescribed opioid medications for pain. One case of alcohol
      dependence and 3 cases of alcohol abuse were found. Psychiatric diagnoses,
      excluding substance use disorders, predominated as follows: major depressive
      disorder, 44.4%; posttraumatic stress disorder, 29.2%; and obsessive-compulsive
      personality disorder, 62.5%. CONCLUSIONS: Certain populations of patients with
      complex nocioceptive, neuropathic, and myofascial pain syndromes may have a lower
      prevalence of substance use disorders than the general population. They also may
      have concurrent psychiatric disorders, which should be evaluated and treated
      concomitantly as part of their chronic pain treatment. Rates reported for
      possible obsessive-compulsive personality disorder may be reflective of patients'
      expected preoccupation with pain complaints. The low prevalence of substance use
      disorders may be attributable to the severity of their illness, the patients'
      inability to achieve pain relief and obtain pain medications easily, as well as
      their persistence in pursuing accurate diagnoses and treatment. Roughly one-third
      were not currently prescribed opioids at the time of the study, perhaps
      undercutting risk for opioid use disorder rates. Additionally, due to the
      tertiary referral nature of this clinic, patients with behaviors believed to be a
      manifestation of opioid use disorder may have already been selected out prior to
      referral to this clinic. A major limitation of this study was that it relied on a
      self-report assessment instrument and there were no drug screen findings to
      report. Such unique clinic characteristics and study limitations may narrow
      generalizability of results. Despite the low prevalence of substance use
      disorders observed for this clinic population, these patients must be
      continuously monitored for abuse, misuse, and diversion of their medication.

PMID- 23131840
TI  - Effect of form cues on 1D and 2D motion pooling.
AB  - Local-motion information can provide either 1-dimensional (1D) or 2-dimensional
      (2D) solutions. 1D signals occur when the aperture problem has not been solved,
      so each signal is an estimate of the local-orthogonal component of the object's
      motion. 2D signals occur when the aperture problem has been solved, so each
      signal is an estimate of the object's motion. Previous research (JoV, 2009, 9, 1
      25) has shown that 1D and 2D signals are pooled differently, via intersection-of
      constraints (IOC) and vector-average processes, respectively. Previous research
      (e.g. Vis. Res., 2003, 2290-2301) has also indicated that form cues can influence
      how motion signals are perceived. We investigated whether forms cues can affect
      the pooling of motion signals and whether they differentially affect the pooling
      of 1D and 2D signals. Global-Gabor (GG) and global-plaid (GP) stimuli were used.
      These stimuli consist of multiple apertures that contain either Gabors or plaids,
      respectively. In the GG stimulus the global solution is defined by having the
      Gabor carriers move (1D signals) such that they are consistent with a single IOC
      defined solution. In the GP stimuli the plaid motion (2D signals) are consistent
      with a vector-average solution defined by a Gaussian distribution. Form cues can
      be introduced by adding orientation information to the apertures that is either
      consistent (aligned with) or inconsistent (orthogonal to) with the global
      solution. With the 1D stimuli, form cues affect how the motion signals are
      pooled, with motion being perceived in the direction defined by the orientation
      cue. Orientation cues had no direct effect on the pooling of the 2D signals.

PMID- 23131841
TI  - A United Nations Global Health Panel for Global Health Governance: a commentary
      on Mackey.

PMID- 23131842
TI  - Perineal hernia repair using an autologous tunica vaginalis communis in nine
      intact male dogs.
AB  - Perineal hernia in dogs is very problematic and mostly requires surgical
      reconstruction of the weak pelvic diaphragm. Tissue or synthetic grafts have been
      used for the correction after failure of the conventional herniorrhaphy. Aim of
      this clinical trial was to assess the possible use of the autologous tunica
      vaginalis communis as a free graft for perineal hernia repair in intact male
      dogs. Seven unilateral and 2 bilateral perineal hernias in nine intact male dogs
      free from testicular and scrotal neoplasms were included in this study. The
      median surgical time for unilateral herniorrhaphy was 75 min. The median follow
      up time was 13 months. The success of the autografting, based on no recurrence
      and comfort of the animals during urination and defecation, was found in ten of
      11 hernias; giving a success rate of 90.91%. One hernia (9.09%) recurred 10 days
      after surgery. Histopathological examination of the apposing area between the
      graft and the adjacent tissue, taken during the repair of the recurred case at
      day 20, revealed neovascularization and connective tissue ingrowth. In
      conclusion, the tunica vaginalis autograft can be used for perineal herniorrhaphy
      in intact male dogs.

PMID- 23131844
TI  - Sexy DEG/ENaC channels involved in gustatory detection of fruit fly pheromones.
AB  - Hydrocarbon pheromones on the cuticle of Drosophila melanogaster modulate the
      complex courtship behavior of males. Recently, three members of the
      degenerin/epithelial Na+ channel (DEG/ENaC) family of sodium channel subunits,
      Ppk25, Ppk23, and Ppk29 (also known as Nope), have been shown to function in
      gustatory perception of courtship-modulating contact pheromones. All three
      proteins are required for the activation of male courtship by female pheromones.
      Specific interactions between two of them have been demonstrated in cultured
      cells, suggesting that, in a subset of cells where they are coexpressed, these
      three subunits function within a common heterotrimeric DEG/ENaC channel. Such a
      DEG/ENaC channel may be gated by pheromones, either directly or indirectly, or
      alternatively may control the excitability of pheromone-sensing cells. In
      addition, these studies identify taste neurons that respond specifically to
      courtship-modulating pheromones and mediate their effects on male behavior. Two
      types of pheromone-sensing taste neurons, F and M cells, have been defined on the
      basis of their specific response to either female or male pheromones. These
      reports set the stage for the dissection of the molecular and cellular mechanisms
      that mediate gustatory detection of contact pheromones.

PMID- 23131843
TI  - Transformation: the next level of regulation.
AB  - The textbook view that a primary sequence determines the unique fold of a given
      protein has been challenged by identification of proteins with variant
      structures, such as prions. Our recent studies revealed that the transcription
      factor RfaH simultaneously changes its topology and function. RfaH is a two
      domain protein whose N-terminal domain binds to transcribing RNA polymerase,
      stimulating its processivity. The alpha-helical C-terminal domain masks the RNA
      polymerase-binding site of the N-terminal domain, preventing unwarranted
      recruitment to genes lacking a specific DNA sequence. Upon binding to its DNA
      target, RfaH domains dissociate, and the C-terminal domain refolds into a beta
      barrel. This dramatic transformation allows binding to the ribosomal protein S10
      and subsequent recruitment of a ribosome, coupling transcription and translation.
      We define RfaH as first example of "transformer proteins", in which two
      alternative structural states have distinct cellular functions and hypothesize
      that transformer proteins may be widespread in nature.

PMID- 23131845
TI  - Grb2, a double-edged sword of receptor tyrosine kinase signaling.
AB  - Receptor tyrosine kinases (RTKs) exhibit basal tyrosine phosphorylation and
      activity in the absence of ligand stimulation, which has been attributed to the
      "leaky" nature of tyrosine kinase autoinhibition and stochastic collisions of
      receptors in the membrane bilayer. This basal phosphorylation does not produce a
      signal of sufficient amplitude and intensity to manifest in a biological response
      and hence is considered to be a passive, futile process that does not have any
      biological function. This paradigm has now been challenged by a study showing
      that the basal phosphorylation of RTKs is a physiologically relevant process that
      is actively inhibited by the intracellular adaptor protein growth factor receptor
      bound 2 (Grb2) and serves to "prime" receptors for a rapid response to ligand
      stimulation. Grb2 is conventionally known for playing positive roles in RTK
      signaling. The discovery of a negative regulatory role for Grb2 reveals that this
      adaptor acts as a double-edged sword in the regulation of RTK signaling.

PMID- 23131846
TI  - Key roles for the lipid signaling enzyme phospholipase d1 in the tumor
      microenvironment during tumor angiogenesis and metastasis.
AB  - Angiogenesis inhibitors, which target tumor cells, confer only short-term
      benefits on tumor growth. We report that ablation of the lipid signaling enzyme
      phospholipase D1 (PLD1) in the tumor environment compromised the
      neovascularization and growth of tumors. PLD1 deficiency suppressed the
      activation of Akt and mitogen-activated protein kinase signaling pathways by
      vascular endothelial growth factor in vascular endothelial cells, resulting in
      decreased integrin-dependent cell adhesion to, and migration on, extracellular
      matrices, as well as reduced tumor angiogenesis in a xenograft model. In
      addition, mice lacking PLD1 incurred fewer lung metastases than did wild-type
      mice. Bone marrow transplantation and binding studies identified a platelet
      derived mechanism involving decreased tumor cell-platelet interactions, in part
      because of impaired activation of alphaIIbbeta3 integrin in platelets, which
      decreased the seeding of tumor cells into the lung parenchyma. Treatment with a
      small-molecule inhibitor of PLD1 phenocopied PLD1 deficiency, efficiently
      suppressing both tumor growth and metastasis in mice. These findings reveal that
      PLD1 in the tumor environment promotes tumor growth and metastasis and, taken
      together with previous reports on the roles of PLD in tumor cell-intrinsic
      adaptations to stress, suggest the potential use of PLD inhibitors as cancer
      therapeutics.

PMID- 23131847
TI  - Proliferative and antiapoptotic signaling stimulated by nuclear-localized PDK1
      results in oncogenesis.
AB  - Enhanced activation of phosphoinositide 3-kinase (PI3K) is a hallmark of many
      human tumors because it promotes cell proliferation and survival through several
      mechanisms. One of these mechanisms is the phosphorylation of the serine and
      threonine kinase Akt at the cytosolic side of the plasma membrane by
      phosphoinositide-dependent protein kinase 1 (PDK1), which is recruited and
      activated by binding to the phosphoinositides produced by PI3K. We previously
      demonstrated increased nuclear accumulation of PDK1 in cells with enhanced PI3K
      activity. We report that nuclear PDK1 promoted cell proliferation by suppressing
      FOXO3A-dependent transcription of the gene encoding p27Kip1 (an inhibitor of cell
      cycle progression), whereas it enhanced cell survival by inhibiting the
      activation of c-Jun amino-terminal kinase. Cells with nuclear-localized PDK1
      showed anchorage-independent growth, and when injected into mice, these cells
      induced the formation of solid tumors. In human prostate tumors, cytoplasmic
      localization of PDK1 correlated only with early-stage, low-risk tumors, whereas
      nuclear PDK1 localization correlated with high-risk tumors. Together, our
      findings suggest a role for nuclear-translocated PDK1 in oncogenic cellular
      transformation and tumor progression in mice and humans.

PMID- 23131848
TI  - Introducing a new ASGCT forum for publication of methodology and clinical
      development in gene, cell, and oligonucleotide therapies.

PMID- 23131851
TI  - RNAi joins the "Singles Club".

PMID- 23131852
TI  - Converting pathological cells to therapeutic ones: an odyssey through
      pluripotency.

PMID- 23131853
TI  - rAAV-mediated tumorigenesis: still unresolved after an AAV assault.

PMID- 23131854
TI  - A new vision of mesenchymal stromal cells.

PMID- 23131855
TI  - Pulmonary thrombosis associated with antidiuretic hormone replacement therapy due
      to secondary diabetes insipidus after traumatic brain injury: A case report.
AB  - INTRODUCTION: Diabetes insipidus is a well-recognized complication of traumatic
      brain injury. The majority of patients with post-traumatic diabetes insipidus
      will require antidiuretic hormone (ADH) replacement therapy and tend to show
      dehydration. On the other hand, some negative effects of ADH on blood
      coagulation, such as increased platelet cohesion and the promotion of von
      Willebrand factor release, have also been reported. However, the incidence of
      thrombosis during antidiuretic hormone replacement therapy is disputed.
      PRESENTATION OF CASE: A case of pulmonary thrombosis associated with ADH
      replacement therapy due to secondary diabetes insipidus after traumatic brain
      injury is presented here. DISCUSSION: In our case, there were three factors that
      may have contributed to the observed thrombosis (dehydration, bed rest for a long
      period and ADH replacement therapy). CONCLUSION: We believe that controlling
      urinary output and monitoring urinary and serum osmotic pressure are necessary
      for the management for diabetes insipidus patients after traumatic brain injury.
      In particular, we must carefully monitor the management of such patients during
      antidiuretic hormone replacement therapy.

PMID- 23131856
TI  - Blonanserin for schizophrenia: systematic review and meta-analysis of double
      blind, randomized, controlled trials.
AB  - BACKGROUND: There is uncertainty about the efficacy and tolerability of
      blonanserin in schizophrenia. METHOD: PubMed, the Cochrane Library databases,
      PsycINFO, and Google Scholar were searched up to September 2012. A systematic
      review and meta-analysis of individual patient data from randomized, controlled
      trials comparing blonanserin with other antipsychotics were conducted. The risk
      ratio (RR), 95% confidence intervals (CI), numbers-needed-to-harm (NNH), and
      weighted mean difference (WMD) were calculated. RESULTS: Four studies (total n =
      1080) were identified (vs. risperidone studies [n = 508], vs. haloperidol studies
      [n = 572]). Comparing blonanserin with other pooled antipsychotics, there were no
      significant differences in the Positive and Negative Syndrome Scale (PANSS) total
      score (p = 0.75), PANSS positive (p = 0.41), PANSS negative (p = 0.09), and PANSS
      general psychopathology subscale scores (p = 0.96), and response rate (p = 0.72).
      However, blonanserin showed greater efficacy in PANSS negative subscale scores
      compared with haloperidol (WMD = -1.29, CI = -2.29 to -0.30, p = 0.01, I(2) =
      0%). No significant differences were found in discontinuation rates between
      blonanserin and other pooled antipsychotics (due to any cause: p = 0.29,
      inefficacy: p = 0.32, adverse events: p = 0.56). Blonanserin had a 0.31 lower
      risk of hyperprolactinemia than the other pooled antipsychotics (CI = 0.20-0.49,
      NNH = not significant). While dizziness (RR = 0.47, CI = 0.23-0.93, NNH = not
      significant) and akathisia (RR = 0.54, CI = 0.32-0.90, NNH = 7) occurred
      significantly less often with blonanserin than with haloperidol, blonanserin had
      a 1.62 higher risk of akathisia than risperidone (CI = 1.18-2.22, NNH = 8)
      [corrected]. CONCLUSION: Our results suggest that although blonanserin has a more
      beneficial effect on negative symptoms than haloperidol, there was a significant
      difference in the adverse events profile between blonanserin and other
      antipsychotics.

PMID- 23131857
TI  - Evaluation of limited sampling models for prediction of oral midazolam AUC for
      CYP3A phenotyping and drug interaction studies.
AB  - BACKGROUND: The area under the concentration-time curve (AUC) after oral
      midazolam administration is commonly used for cytochrome P450 (CYP) 3A
      phenotyping studies. The aim of this investigation was to evaluate a limited
      sampling strategy for the prediction of AUC with oral midazolam. METHODS: A total
      of 288 concentration-time profiles from 123 healthy volunteers who participated
      in four previously performed drug interaction studies with intense sampling after
      a single oral dose of 7.5 mg midazolam were available for evaluation. Of these,
      45 profiles served for model building, which was performed by stepwise multiple
      linear regression, and the remaining 243 datasets served for validation. Mean
      prediction error (MPE), mean absolute error (MAE) and root mean squared error
      (RMSE) were calculated to determine bias and precision RESULTS: The one- to four
      sampling point models with the best coefficient of correlation were the one
      sampling point model (8 h; r (2) = 0.84), the two-sampling point model (0.5 and 8
      h; r (2) = 0.93), the three-sampling point model (0.5, 2, and 8 h; r (2) = 0.96),
      and the four-sampling point model (0.5,1, 2, and 8 h; r (2) = 0.97). However, the
      one- and two-sampling point models were unable to predict the midazolam AUC due
      to unacceptable bias and precision. Only the four-sampling point model predicted
      the very low and very high midazolam AUC of the validation dataset with
      acceptable precision and bias. The four-sampling point model was also able to
      predict the geometric mean ratio of the treatment phase over the baseline (with
      90 % confidence interval) results of three drug interaction studies in the
      categories of strong, moderate, and mild induction, as well as no interaction.
      CONCLUSION: A four-sampling point limited sampling strategy to predict the oral
      midazolam AUC for CYP3A phenotyping is proposed. The one-, two- and three
      sampling point models were not able to predict midazolam AUC accurately.

PMID- 23131858
TI  - CdO nanosheet film with a (200)-preferred orientation with sensitivity to
      liquefied petroleum gas (LPG) at low-temperatures.
AB  - CdO nanosheet film can be synthesized by electrochemical deposition in an ultra
      thin liquid layer by using Cd(NO(3))(2) and HNO(3) as source materials for Cd and
      oxygen respectively. HNO(3) is also used to adjust the pH of the electrolyte.
      Studies on the detailed structure indicate that the synthesized CdO nanosheet
      film has a face-centered cubic structure with (200)-preferred orientation. The
      response of the CdO nanosheet film to liquefied petroleum gas (LPG) at low
      temperature has been significantly improved by the novel structure of film. It
      has exhibited excellent sensitivity and selectivity to LPG at low temperature. A
      new growth mechanism of electrochemical deposition has been proposed to elaborate
      the formation of nanosheet in an ultra-thin liquid layer. The self-oscillation of
      potential in the growth interface and intermediate hydroxide are responsible for
      the formation of nanosheets.

PMID- 23131859
TI  - Do primary nitrosamines form and exist in the gas phase? A computational study of
      CH3NHNO and (CH3)2NNO.
AB  - The reactions of the CH(3)NH and (CH(3))(2)N radicals with NO have been studied
      using quantum chemistry methods to compare the formation and stability of primary
      and secondary nitrosamines. The calculations show that the entrance part of
      potential energy surfaces of CH(3)NHNO and (CH(3))(2)NNO formation are similar,
      and it is concluded that primary amines form nitrosamines under the atmospheric
      conditions. CH(3)NHNO can, in contrast to (CH(3))(2)NNO, undergo isomerization
      via a barrier below the reactants entrance energy to CH(2)NHNOH, which through
      reaction with O(2) eventually leads to formation of CH(2)=NH on a short
      timescale. TDDFT, CASPT2 and MR-CI calculations show little difference between
      the n->pi* transitions in CH(3)NHNO and (CH(3))(2)NNO and that the two molecules
      should have comparable photolysis lifetimes in the atmosphere.

PMID- 23131860
TI  - Streptococcus sanguinis and the sera of patients with Behcet's disease stimulate
      membrane expression of alpha-enolase in human dermal microvascular endothelial
      cells.
AB  - The glycolytic enzyme alpha-enolase is a plasminogen-binding protein that is
      generally found in the cytosolic compartment. However, alpha-enolase can also be
      expressed on cell surfaces following an inflammatory stimulus via an unknown
      mechanism. We investigated the effects of Streptococcus sanguinis (S. sanguinis)
      and the sera of patients with Behcet's disease (BD) on the expression and
      distribution of alpha-enolase in human dermal microvascular endothelial cells
      (HDMECs). HDMECs were stimulated with cultured S. sanguinis and the sera of
      active BD patients. HDMECs incubated for 6, 12 or 24 h were harvested, and the
      membrane and cytoplasmic fractions of proteins were extracted. The expression and
      distribution of alpha-enolase were analyzed using subcellular fractionation and
      immunoblotting. Subcellular localization of alpha-enolase was also assessed by
      immunocytochemistry. S. sanguinis stimulated the expression of alpha-enolase in
      the membranous compartment of HDMECs in a dose-dependent manner. This pattern was
      also observed in HDMECs incubated with BD patients' sera. Although incubation of
      HDMECs with sera from healthy controls increased membrane expression of alpha
      enolase, incubation with BD sera resulted in earlier and higher expression of
      this glycoprotein in the cellular membrane of HDMECs. Immunocytochemistry
      revealed strong immunostaining of alpha-enolase in the cytoplasm and cytoplasmic
      membrane of HDMECs incubated with S. sanguinis or BD patients' sera. In
      conclusions, these results indicate that S. sanguinis infection and the sera of
      BD patients with active disease are inflammatory stimuli that can induce
      membranous alpha-enolase expression in endothelial cells. Membrane-expressed
      alpha-enolase could potentially react with anti-alpha-enolase antibodies in BD
      patients' sera, resulting in increased inflammation.

PMID- 23131861
TI  - Plant species- and status-specific odorant blends guide oviposition choice in the
      moth Manduca sexta.
AB  - The reproductive success of herbivorous insects largely depends on the mother's
      oviposition preference. In nocturnal insects, olfaction is arguably the most
      important sensory modality mediating mate finding, foraging, and host location.
      In most habitats, gravid females select among a number of plants of varying
      suitability, yet assessment of the neuroethological mechanisms underlying odor
      guided choice between host plants is rare. Using a series of behavioral,
      electrophysiological, and chromatographic analyses in the Hawk moth, Manduca
      sexta, we show that gravid females perform a hierarchical choice among host
      plants of different species and qualities using olfactory cues. Both relevant
      plant species and qualities can be distinguished by volatile profiles collected
      from the headspace of these plants, and olfactory sensilla on female antennae
      detect more than half of the about 120 analytically detected volatiles in host
      plant headspace samples. Although olfactory sensory neurons present in antennal
      sensilla are mainly broadly tuned to multiple host compounds, some sensilla
      exhibit species and condition-specific responses. In fact, species and quality
      can be distinguished by the physiologically active components alone. Our findings
      thus suggest that distinguishing characteristics of both host species and quality
      are already represented at the sensory periphery.

PMID- 23131862
TI  - Forcing reality into inappropriate disciplinary frameworks.

PMID- 23131863
TI  - Development and validation of a new statistical model for prognosis of long-term
      graft function after pediatric kidney transplantation.
AB  - BACKGROUND: No adequate statistical model has been established to estimate future
      glomerular filtration rate (GFR) in children after kidney transplantation (KTX).
      Equations based on simple linear regression analysis as used in adults are not
      established in children. METHODS: An optimal prognostic model of GFR was
      generated for 63 children at 3-7 years after KTX. The main regression model for
      prediction of the log-transformed GFR (logGFR) included the mean monthly change
      of GFR in the period 3-24 months after KTX (?GFR), the baseline GFR at 3 months
      (bGFR), and an intercept. Additionally, we investigated if the inclusion of
      cofactors leads to more precise predictions. The model was validated by leave-one
      out cross-validation for years 3-7 after KTX. Prognostic quality was determined
      with the mean squared error (MSE) and mean absolute error (MAE). Results were
      compared with the simple linear regression model used in adults. RESULTS: The
      following statistical model was calculated for every prognosis year (i = 3, ...,
      7):[Formula: see text] [Formula: see text] Comparison of the new statistical
      model and the simple linear model for adults led to relevantly lower MSEs and
      MAEs for the new model (year 7: New model: MSE 0.1, MAE 0.3/adult model: MSE
      1069, MAE 18). The benefit of inclusion of cofactors was not relevant.
      CONCLUSIONS: This statistical model is able to predict long-term graft function
      in children with very high precision.

PMID- 23131864
TI  - The evolving ethics of infant dialysis.
AB  - In this paper, we review ethical issues that arise when families and doctors face
      clinical decisions about renal replacement therapy for an infant with end-stage
      renal disease (ESRD). Over the last 20 years, many centers have begun to
      routinely offer renal replacement therapy. However, doctors and nurses both
      continue to view such therapy as optional, rather than mandatory. We speculate
      that the burdens of therapy on the family, and the uncertainties about
      satisfactory outcomes have led to a situation in which renal replacement therapy
      remains desirable, but non-obligatory. We discuss the reasons why this is likely
      to remain so, and the ways in which renal replacement therapy for infants with
      ESRD is similar to, or different from, other clinical situations in pediatrics.
      Finally, we propose a research agenda to answer questions that are crucial to
      making good ethical decisions about infant dialysis. 

PMID- 23131866
TI  - How much is Kinesio taping a psychological crutch?

PMID- 23131867
TI  - Role of computer-aided detection in very small screening detected invasive breast
      cancers.
AB  - This study aims to assess computer-aided detection (CAD) performance with full
      field digital mammography (FFDM) in very small (equal to or less than 1 cm)
      invasive breast cancers. Sixty-eight invasive breast cancers less than or equal
      to 1 cm were retrospectively studied. All cases were detected with FFDM in women
      aged 49-69 years from our breast cancer screening program. Radiological
      characteristics of lesions following BI-RADS descriptors were recorded and
      compared with CAD sensitivity. Age, size, BI-RADS classification, breast density
      type, histological type of the neoplasm, and role of the CAD were also assessed.
      Per-study specificity and mass false-positive rate were determined by using 100
      normal consecutive studies. Thirty-seven (54.4 %) masses, 17 (25 %)
      calcifications, 6 (8.8 %) masses with calcifications, 7 (10.3 %) architectural
      distortions, and 1 asymmetry (1.5 %) were found. CAD showed an overall
      sensitivity of 86.7 % (masses, 86.5 %; calcifications, 100 %; masses with
      calcifications, 100 %; and architectural distortion, 57.14 %), CAD failed to
      detect 9 out of 68 cases: 5 of 37 masses, 3 of 7 architectural distortions, and 1
      of 1 asymmetry. Fifteen out of 37 masses were hyperdense, and all of them were
      detected by CAD. No association was seen among mass morphology or margins and
      detectability. Per-study specificity and CAD false-positive rate was 26 % and
      1.76 false marks per study. In conclusion, CAD shows a high sensitivity and a low
      specificity. Lesion size, histology, and breast density do not influence
      sensitivity. Mammographic features, mass density, and thickness of the spicules
      in architectural distortions do influence.

PMID- 23131868
TI  - Peptostreptococcus canis sp. nov., isolated from subgingival plaque from canine
      oral cavity.
AB  - A polyphasic taxonomic study was performed on two strains of an unknown Gram
      positive, asaccharolytic, nonspore-forming, obligately anaerobic coccus-shaped
      bacterium isolated from oral subgingival plaque of Labrador retriever dogs.
      Comparative 16S rRNA gene sequencing confirmed that these isolates were highly
      related to each other and formed a hitherto unknown linage within the clostridial
      rRNA XI cluster of organisms. Pairwise analysis demonstrated that the novel
      organism to be most closely related to members of the genus Peptostreptococcus
      with 16S rDNA gene sequence similarity values between 92.8% and 96.7%,
      respectively. The G + C DNA base composition was 30.8 mol% and the major cellular
      fatty acids included iso-C(14:0,) iso-C(16:0), and iso-C(16:0 DMA). Based on
      biochemical, chemotaxonomic, and phylogenetic evidence it is proposed that the
      unknown bacterium be classified as a new species, Peptostreptococcus canis sp.
      nov. The type strain is CCUG 57081(T).

PMID- 23131869
TI  - Magnetic properties of two 2D complexes based on 1D chain containing
      [Fe(bpy)(CN)4]- unit.
AB  - Two heterobimetallic 2-dimensional layer complexes, {[Fe(bpy)(CN)(4)](2)M(4,4'
      bipyridine)}.4H(2)O [bpy = 2,2'-bipyridine, M = Mn (1), Cu (2)] have been
      prepared by diffusion and their structures determined by single crystal X-ray
      diffraction. 1 and 2 are isomorphous, made of neutral bimetallic
      [Fe(bpy)(CN)(4)](2)M(4,4'-bipyridine)] layers and uncoordinated water molecules
      located between the layers. Interestingly, complex 2 shows the compression of the
      Jahn-Teller distortion around the copper(II) ion. Magnetic investigation shows
      antiferromagnetic coupling between the manganese(II) and iron(III) ions mediated
      by bridging CN(-) in 1, while ferromagnetic coupling between the copper(II) and
      iron(III) ions is seen in 2. Both complexes 1 and 2 reveal a metamagnetic-like
      behaviour with different critical fields (H(c), at 1.8 K): 2.0 kOe (1) and 3.2
      kOe (2). The weak interchain antiferromagnetic interaction can be illustrated by
      the spin-polarization mechanism.

PMID- 23131871
TI  - Feasibility and impact of a computer-guided consultation on  guideline-based
      management of COPD in general practice.
AB  - BACKGROUND: Applying guidelines is a universal challenge that is often not met.
      Intelligent software systems that facilitate real-time management during a
      clinical interaction may offer a solution. AIMS: To determine if the use of a
      computer-guided consultation that facilitates the National Institute for Health
      and Clinical Excellence-based chronic obstructive pulmonary disease (COPD)
      guidance and prompts clinical decision-making is feasible in primary care and to
      assess its impact on diagnosis and management in reviews of COPD patients.
      METHODS: Practice nurses, one-third of whom had no specific respiratory training,
      undertook a computer-guided review in the usual consulting room setting using a
      laptop computer with the screen visible to them and to the patient. A total of
      293 patients (mean (SD) age 69.7 (10.1) years, 163 (55.6%) male) with a diagnosis
      of COPD were randomly selected from GP databases in 16 practices and assessed.
      RESULTS: Of 236 patients who had spirometry, 45 (19%) did not have airflow
      obstruction and the guided clinical history changed the primary diagnosis from
      COPD in a further 24 patients. In the 191 patients with confirmed COPD, the
      consultations prompted management changes including 169 recommendations for
      altered prescribing of inhalers (addition or discontinuation, inhaler dose or
      device). In addition, 47% of the 55 current smokers were referred for smoking
      cessation support, 12 (6%) for oxygen assessment, and 47 (24%) for pulmonary
      rehabilitation. CONCLUSIONS: Computer-guided consultations are practicable in
      general practice. Primary care COPD databases were confirmed to contain a
      significant proportion of incorrectly assigned patients. They resulted in
      interventions and the rationalisation of prescribing in line with
      recommendations. Only in 22 (12%) of those fully assessed was no management
      change suggested. The introduction of a computer-guided consultation offers the
      prospect of comprehensive guideline quality management.

PMID- 23131872
TI  - Genes affected by mouse mammary tumor virus (MMTV) proviral insertions in mouse
      mammary tumors are deregulated or mutated in primary human mammary tumors.
AB  - The accumulation of mutations is a contributing factor in the initiation of
      premalignant mammary lesions and their progression to malignancy and metastasis.
      We have used a mouse model in which the carcinogen is the mouse mammary tumor
      virus (MMTV) which induces clonal premalignant mammary lesions and malignant
      mammary tumors by insertional mutagenesis. Identification of the genes and
      signaling pathways affected in MMTV-induced mouse mammary lesions provides a
      rationale for determining whether genetic alteration of the human orthologues of
      these genes/pathways may contribute to human breast carcinogenesis. A high
      throughput platform for inverse PCR to identify MMTV-host junction fragments and
      their nucleotide sequences in a large panel of MMTV-induced lesions was
      developed. Validation of the genes affected by MMTV-insertion was carried out by
      microarray analysis. Common integration site (CIS) means that the gene was
      altered by an MMTV proviral insertion in at least two independent lesions arising
      in different hosts. Three of the new genes identified as CIS for MMTV were
      assayed for their capability to confer on HC11 mouse mammary epithelial cells the
      ability for invasion, anchorage independent growth and tumor development in nude
      mice. Analysis of MMTV induced mammary premalignant hyperplastic outgrowth (HOG)
      lines and mammary tumors led to the identification of CIS restricted to 35 loci.
      Within these loci members of the Wnt, Fgf and Rspo gene families plus two linked
      genes (Npm3 and Ddn) were frequently activated in tumors induced by MMTV. A
      second group of 15 CIS occur at a low frequency (2-5 observations) in mammary
      HOGs or tumors. In this latter group the expression of either Phf19 or Sdc2 was
      shown to increase HC11 cells invasion capability. Foxl1 expression conferred on
      HC11 cells the capability for anchorage-independent colony formation in soft agar
      and tumor development in nude mice. The published transcriptome and nucleotide
      sequence analysis of gene expression in primary human breast tumors was
      interrogated. Twenty of the human orthologues of MMTV CIS associated genes are
      deregulated and/or mutated in human breast tumors.

PMID- 23131873
TI  - A case of valproate toxicity related to isoniazid.

PMID- 23131874
TI  - Recurrence of panic attacks after brucellosis treatment--highly probable
      citalopram and rifampin drug interaction.

PMID- 23131875
TI  - Enhanced ziprasidone combination therapy effectiveness in obese compared to
      nonobese patients with bipolar disorder.
AB  - OBJECTIVE: To assess longer-term ziprasidone effectiveness in obese and non-obese
      patients with bipolar disorder (BD). METHODS: Outpatients assessed with the
      Systematic Treatment Enhancement Program for BD Affective Disorders Evaluation
      and monitored with the Systematic Treatment Enhancement Program for BD Clinical
      Monitoring Form received open ziprasidone. RESULTS: Eighty-two patients (39
      patients with BD I, 39 patients with BD II, and 4 patients with BD not otherwise
      specified; mean age, 41.1 years; females, 78.0%; obese, 48.8%) received
      ziprasidone combined with an average of 3.6 (in 74.4% at least 3) other
      prescription psychotropics and 1.2 prescription nonpsychotropics. Mean (median)
      ziprasidone final dose and duration were 134.3 (150) mg/d and 489 (199.5) days,
      respectively. Ziprasidone yielded in obese compared to nonobese patients less
      discontinuation (42.5% vs 71.4%, P = 0.01), albeit with a higher rate of addition
      of subsequent psychotropic medication (62.5% vs 35.7%, P = 0.03). Moreover, obese
      compared to nonobese patients had a higher rate of shift to final-visit euthymia
      (27.5% vs 0.0%, P = 0.0002), and more weight loss (-20.7 lbs vs -0.6 lbs, P =
      0.001), and obese (but not nonobese) patients had significant improvements in
      mean Clinical Global Impression-Severity of Illness (decreased 0.6 points; P =
      0.03) and Global Assessment of Functioning (increased 3.3 points, P = 0.01)
      scores. Weight change correlated significantly with Global Assessment of
      Functioning change (P = 0.047) but not with Clinical Global Impression-Severity
      of Illness change. Limitations are small sample size and open-label,
      uncontrolled, observational design. CONCLUSION: Controlled and additional
      observational studies seem warranted to confirm our preliminary findings
      suggesting ziprasidone may be more effective in obese compared to nonobese
      patients with BD already receiving combination pharmacotherapy.

PMID- 23131876
TI  - Optimizing the early prediction model for symptomatic remission with short-term
      treatment for schizophrenia.
AB  - Remission seems achievable for a portion of schizophrenic patients. This study
      aimed to identify the early predictors for remission and to establish an optimal
      prediction model. One hundred thirty-five acutely ill schizophrenic inpatients
      received 150-mg/d zotepine treatment for 4 weeks. Psychopathologic severity was
      assessed weekly using the Brief Psychiatric Rating Scale (BPRS). Symptomatic
      remission was defined according to the consensus criteria proposed by Andreasen
      et al. Backward stepwise logistic regression model was used to obtain the early
      predictors. The receiver operating characteristic curve was used to determine the
      cutoff point of predictors. The study was conducted from June 2004 to April 2005.
      Twenty-one (21.0%) of 100 completers remitted after 4 weeks of treatment. The
      most influential predictors for ultimate remission were percentage of BPRS score
      reduction at week 2 and BPRS remission-items score at week 2. Brief Psychiatric
      Rating Scale score reduction at week 2 of 35% and BPRS remission-items score of
      18 at week 2 seemed to be the optimal cutoff points. They provided a sensitivity
      of 62% and 84% and a specificity of 86% and 65%. Patients with less than a 35%
      BPRS score reduction and a BPRS remission-items score larger than 18 during the
      first 2 weeks of treatment were unlikely to reach a final remission. Whether the
      finding can be extrapolated to other validated assessment scales and other
      antipsychotics require further studies.

PMID- 23131877
TI  - Electroconvulsive therapy and clozapine in adolescents with schizophrenia
      spectrum disorders: is it a safe and effective combination?
AB  - OBJECTIVE: To evaluate the safety and effectiveness of the combination of
      electroconvulsive therapy (ECT) and clozapine compared to ECT with other
      antipsychotics or benzodiazepines in a sample of adolescents diagnosed with
      schizophrenia spectrum disorders. METHODS: Data regarding 28 adolescent subjects
      aged 13 to 18 with diagnoses of schizophrenia spectrum disorders according to the
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text
      Revision and treated with ECT were retrospectively collected. Twelve subjects
      were also treated with clozapine and 16 with other antipsychotics or
      benzodiazepines during ECT course and follow-up. Electroconvulsive therapy
      parameters and adverse effects were assessed using a systematic protocol.
      Positive and Negative Syndrome Scale and Clinical Global Impression scores before
      ECT and after acute ECT, and rate of rehospitalization during 1-year follow-up
      were used to assess effectiveness. Response was defined as a 20% decrease in
      Positive and Negative Syndrome Scale scores. RESULTS: No differences were
      observed in the mean charge needed to induce seizure and electroencephalographic
      duration, but there was a slight difference in the current used. The nonclozapine
      group showed greater restlessness and agitation, although no differences were
      found in other adverse effects. The percentage of responders was similar: 66.7%
      in the clozapine group and 68.8% in the nonclozapine group. However, the rate of
      rehospitalization was lower in the patients treated with clozapine during 1-year
      follow-up (7.1%) compared to that of the nonclozapine group (58.3%) (P = 0.009).
      CONCLUSIONS: The main findings of this study were that combining ECT with
      clozapine, compared to ECT with other antipsychotics or benzodiazepines, was safe
      and that both treatments were equally effective. Charges needed to induce seizure
      were similar in both groups. Patients treated with clozapine during 1-year follow
      up had a lower rate of rehospitalization.

PMID- 23131878
TI  - Identifying potential adverse effects by patients' ratings: a proof-of-concept
      study of a novel approach.
AB  - OBJECTIVE: Methods to evaluate adverse effects of medications are significantly
      underdeveloped compared to those for efficacy. In this pilot proof-of-concept
      study, we preliminarily compared a novel approach-the Symptom Assessment Tool
      (SAT)-to a systematic and detailed assessment by a physician for identifying
      symptoms that were potentially adverse effects (sensitivity) and excluding
      symptoms that were unlikely to be adverse effects (specificity). METHODS: A
      symptom inventory and rating of symptom severity were completed before starting a
      psychotropic medication (or increasing its dose), and again 2 weeks later. Each
      symptom was systematically assessed by the patient-rated SAT and by a physician
      and was classified as either a potential or unlikely adverse effect. The primary
      analysis compared the classification of symptoms by the SAT to that by the
      physician. Potential adverse effects were also subcategorized as possible or
      probable adverse effects. RESULTS: A sample of 193 symptoms from 15 adults was
      evaluated, only 37.3% of which were considered potential adverse effects by the
      physician. Sensitivity of the SAT compared to physician's assessment was 90.3%
      for potential adverse effects and 97.5% for the subgroup of probable adverse
      effects. The SAT correctly identified 63.6% of the symptoms as unlikely adverse
      effects (specificity), and its negative predictive value was 91.7%. CONCLUSIONS:
      The SAT, appropriate for its intended use as a screening tool, had high
      sensitivity and moderate specificity and could present physicians with a limited
      number of potential adverse effects for further assessment and intervention.
      Further evaluation and refinement of this approach is warranted.

PMID- 23131879
TI  - Trajectories of agouti-related protein and leptin levels during antipsychotic
      associated weight gain in patients with schizophrenia.
AB  - OBJECTIVE: Some but not all second-generation antipsychotics can induce
      considerable weight gain and metabolic syndrome. Although the exact biochemical
      mechanisms for these adverse effects are unclear, appetite-regulating
      neuropeptides of the central nervous system are thought to be implicated in this
      process. The hypothalamic mediator Agouti-related protein (AGRP) is inhibited by
      leptin and was shown to increase food intake. The aim of the present study was to
      investigate the trajectory of AGRP levels during antipsychotic-induced weight
      gain. METHODS: As part of a controlled prospective clinical study, we determined
      indicators of body fat mass, plasma AGRP, and leptin levels in 16 patients with
      schizophrenia treated with ziprasidone and 21 patients with schizophrenia treated
      with olanzapine. Measurements by enzyme-linked immunosorbent assay were obtained
      before treatment (T0), after 4 weeks (T1), and after 3 months (T2) of treatment.
      RESULTS: Whereas body mass index and leptin levels increased in patients treated
      with olanzapine compared to patients treated with ziprasidone, plasma AGRP levels
      did not differ among the treatment groups and did not change over time.
      Associations between AGRP and fat mass as well as appetite were disrupted in the
      olanzapine-treated patients but not in the ziprasidone group. CONCLUSION: Future
      studies are needed to test whether the lack of a decrease in AGRP levels during
      weight gain in patients treated with olanzapine could perpetuate adverse
      metabolic long-term effects.

PMID- 23131880
TI  - Valproic acid treatment is associated with altered leukocyte subset development.
AB  - Valproic acid (VPA) has been used for decades in the treatment of epilepsy and
      psychiatric disorders, and the long-term use of VPA is regularly accompanied by
      hematological toxicity, including neutropenia. More recently, it has been
      demonstrated that VPA can be used as a histone deacetylase inhibitor (HDACi) for
      the treatment of hematological malignancies. In order to determine the specific
      effects of VPA in both hematological malignancies and normal hematopoiesis,
      recent studies have demonstrated that VPA treatment affects the differentiation
      of normal myeloid progenitors in vitro. In this study, we demonstrate that in a
      large patient population treated for neurological or psychiatric disorders, VPA
      treatment affects neutrophil as well as lymphocyte subset counts.

PMID- 23131881
TI  - No significant association between genetic variants in 7 candidate genes and
      response to methylphenidate treatment in adult patients with ADHD.
AB  - Results from pharmacogenetic investigations of methylphenidate (MPH) response in
      patients with ADHD are still inconsistent, especially among adults. This study
      investigates the role of genetic variants (SLC6A4, HTR1B, TPH2, DBH, DRD4, COMT,
      and SNAP25) in the response to MPH in a sample of 164 adults. Genes were chosen
      owing to previous evidence for an influence in ADHD susceptibility. No
      significant differences in allele or genotype frequencies between MPH responders
      and nonresponders were detected. In conclusion, our findings do not support an
      effect of these genes in the pharmacogenetics of MPH among adults with ADHD.

PMID- 23131882
TI  - Follow-up study of a pharmacovigilance signal: no evidence of increased risk with
      risperidone of pituitary tumor with mass effect.
AB  - INTRODUCTION: Pharmacovigilance studies of spontaneous adverse event report
      databases are used to raise hypotheses about potential safety events. Such
      studies have found a disproportionately higher number of pituitary tumor reports
      for risperidone. Because there is a high prevalence of clinically "silent"
      pituitary adenomas, any increased workup in risperidone users, for example,
      secondary to hyperprolactinemia, might account for the increased reports. We
      undertook a detailed study of medical record-confirmed newly diagnosed pituitary
      tumors with mass effect in patients prescribed antipsychotics to evaluate the
      effect of risperidone. METHODS: We conducted retrospective studies in 2 large
      administrative health care databases with access to medical records. Patients
      were classified into risperidone or other atypical antipsychotic exposure groups.
      Records with administrative codes indicative of possible cases in the follow-up
      period were reviewed to confirm the diagnosis of new pituitary tumor and presence
      of mass effects. RESULTS: The hazard ratio of confirmed pituitary tumors with
      mass effect was 1.0 (95% confidence interval, 0.5-1.9). Whereas the precision of
      the hazard ratio was limited by low event rates, despite examination of 409,823
      patients' records, ancillary analyses supported the interpretation of no elevated
      risk. Evidence was found for detection bias that may explain previous
      pharmacovigilance findings. DISCUSSION: There was no evidence of increased risk
      of pituitary tumor with mass effect with risperidone in either cohort or case
      control analyses. We cannot rule out a small risk (<2-fold), or a risk that may
      develop with additional years of exposure or follow-up, or a risk of
      microadenomas or prolactinomas.

PMID- 23131883
TI  - Common use of antipsychotic polypharmacy in older Asian patients with
      schizophrenia (2001-2009).
AB  - OBJECTIVE: The aim of this study was to survey the use of antipsychotic
      polypharmacy (APP) in older Asian patients with schizophrenia and examine its
      demographic and clinical correlates. METHODS: Information on hospitalized
      patients with schizophrenia aged 55 or older was extracted from the database of
      the Research on Asian Psychotropic Prescription Patterns study. Data on 1439
      patients in 6 Asian countries and territories including China, Hong Kong, Japan,
      Korea, Singapore, and Taiwan were analyzed. Sociodemographic and clinical
      characteristics and antipsychotic prescriptions were recorded using a
      standardized protocol and data collection procedure. RESULTS: The frequency of
      APP prescription was 51.6% in the pooled sample with wide intercountry
      variations. Multiple logistic regression analysis of the whole sample showed that
      patients on APP had higher antipsychotic doses and also were more likely to
      receive first-generation antipsychotics. CONCLUSIONS: Use of APP was common in
      older Asian patients with schizophrenia. Given the limited evidence supporting
      its efficacy, the potentially severe side effects and high costs, APP should be
      used with caution in this population. The reasons for and outcomes of the use of
      APP in this patient population merit further exploration.

PMID- 23131885
TI  - N-acetylcysteine add-on treatment in refractory obsessive-compulsive disorder: a
      randomized, double-blind, placebo-controlled trial.
AB  - OBJECTIVE: This study aimed to evaluate the efficacy and safety of N
      acetylcysteine, a glutamate-modulating agent, in patients with treatment
      refractory obsessive-compulsive disorder as an adjunct to serotonin reuptake
      inhibitor treatment. METHODS: Forty-eight patients (36 women; mean +/- SD age,
      30.93 +/- 4.99) with obsessive-compulsive disorder who failed to respond to a
      course of serotonin reuptake inhibitor treatment were randomized to a 12-week
      intervention period of N-acetylcysteine (up to 2400 mg/d) or placebo. Primary
      outcome measures were the change in Yale-Brown Obsessive Compulsive Scale (Y
      BOCS) score from baseline to end point and the rate of full response in each
      group at the end of trial. Full response was defined as 35% or greater reduction
      in Y-BOCS score from baseline. RESULTS: Changes of Y-BOCS score were different
      over time (P < 0.001) and between groups (P < 0.001). N-acetylcysteine-assigned
      patients showed significantly improved mean Y-BOCS score (P = 0.003) and Clinical
      Global Impression-Severity of Illness scale score (P = 0.01) but not Clinical
      Global Impression-Improvement scale score at study end point. Of the patients in
      the N-acetylcysteine group, 52.6% were full responders at the end of the study,
      which was significantly higher than 15% of the patients in the placebo group (P =
      0.013). CONCLUSION: This trial suggests that N-acetylcysteine may be a safe and
      effective option to augment standard treatment in patients with refractory
      obsessive-compulsive disorder.

PMID- 23131886
TI  - Long-term effect of haloperidol, olanzapine, and risperidone on plasma prolactin
      levels in patients with first-episode psychosis.
AB  - OBJECTIVE: The main goal of this study was to assess the long-term effect of
      haloperidol, olanzapine, and risperidone on serum prolactin levels in a
      naturalistically treated first-episode psychosis population. METHODS: Patients
      included in this study were drawn from a prospective, randomized, open-label
      clinical trial. Prolactin levels were measured in 110 patients with medication
      naive first-episode psychosis at baseline, 3 months, and 1 year. RESULTS: A
      repeated-measures analysis of variance revealed a significant difference between
      treatments (F = 17.28, P < 0.001). At 1-year follow-up, most patients in the
      haloperidol and olanzapine arms had prolactin values that fell within the
      reference range. Patients treated with risperidone experienced a significant
      increase at 3 months resulting in prolactin levels above the reference range in
      90% of men and 87% of women. The levels showed a tendency to decrease at 1 year,
      although still more than 70% of the values remained above the normative range.
      Sexual adverse drug reactions at 1 year assessed by the Udvalg for Kliniske
      Undersogelser scale showed that a higher percentage (39.3%) of patients had
      symptoms in the risperidone group compared to the olanzapine group (24%) or
      haloperidol group (20%), but the difference did not reach statistical
      significance (P = 0.281). CONCLUSION: Olanzapine and haloperidol treatments do
      not significantly affect serum prolactin levels at long term. After 1 year,
      elevated prolactin levels persist in most patients treated with risperidone.

PMID- 23131884
TI  - A randomized, controlled, pilot study of acamprosate added to escitalopram in
      adults with major depressive disorder and alcohol use disorder.
AB  - We sought to examine the efficacy and safety of acamprosate augmentation of
      escitalopram in patients with concurrent major depressive disorder (MDD) and
      alcohol use disorders. Twenty-three adults (43% female; mean +/- SD age, 46 +/-
      14 years) were enrolled and received 12 weeks of treatment with psychosocial
      support; escitalopram, 10 to 30 mg/d; and either acamprosate, 2000 mg/d (n = 12),
      or identical placebo (n = 11). Outcomes included change in clinician ratings of
      depressive symptoms, MDD response and remission rates, changes in frequency and
      intensity of alcohol use, retention rates, and adverse events. Twelve subjects
      (acamprosate, n = 7; placebo, n = 5) completed the study. There was significant
      mean reduction in ratings of depressive symptoms from baseline in both treatment
      arms (P < 0.05), with no significant difference between the groups. Those in the
      acamprosate group had a 50% MDD response rate and a 42% remission rate, whereas
      those in the placebo arm had a 36% response and remission rate (not significant).
      Those assigned to acamprosate had significant reduction in number of drinks per
      week and drinks per month during the trial, whereas those assigned to placebo
      demonstrated no significant change in any alcohol use parameter, but the between
      group difference was not significant. There were no significant associations
      between change in depressive symptoms and change in alcohol use. Attrition rates
      did not differ significantly between the 2 arms. Acamprosate added to
      escitalopram in adults with MDD and alcohol use disorders was associated with
      reduction in the frequency of alcohol use. The present study was not powered to
      detect superiority versus placebo. Further study in a larger sample is warranted.

PMID- 23131887
TI  - Pregabalin misuse-related issues; intake of large dosages, drug-smoking
      allegations, and possible association with myositis: two case reports.

PMID- 23131888
TI  - Low-dose clozapine exacerbates and then improves mood in a patient with
      schizophrenia and history of surgical removal of an intraventricular meningioma.

PMID- 23131889
TI  - Drugs associated with restless legs syndrome: a case/noncase study in the French
      Pharmacovigilance Database.
AB  - BACKGROUND: Several case reports have suggested that drugs could induce restless
      legs syndrome. However, no systematic review of this adverse drug reaction (ADR)
      in a pharmacovigilance database has been published. OBJECTIVE: To assess the
      frequency of restless legs syndrome in the French Pharmacovigilance Database.
      METHODS: We selected all ADR reports from January 1, 1984 to December 31, 2009
      coded as restless legs syndrome. Restless legs syndrome diagnosis was validated
      from case descriptions. Using a case/noncase approach, reporting odds ratio and
      95% confidence interval were calculated for "suspected'' drugs with 2 or more
      observations. RESULTS: Twenty-six ADR reports were found. Four cases were
      excluded because of alternative diagnosis. Fourteen cases were women (64%).
      Median age was 57. Most frequently suspected drugs were antidepressants
      (reporting odds ratio, 15.9 [6.4-39.7]; amitriptyline, escitalopram, mianserine,
      mirtazapine, duloxetine), neuroleptics (17.8 [6.1-51.7]; thioridazine, loxapine,
      risperidone, aripiprazole) or tramadol (18.2 [6.3-52.8]). CONCLUSIONS: Restless
      legs syndrome is a very rare ADR that was more frequently reported in association
      with antidepressants, neuroleptics, or tramadol.

PMID- 23131890
TI  - Cognitive effects of a single dose of atypical antipsychotics in healthy
      volunteers compared with placebo or haloperidol.
AB  - Cognitive dysfunction in patients with schizophrenia is a strong correlate of
      poor outcome than any other symptom domain. To have greater knowledge about the
      effects of antipsychotics on cognitive function, subjects of this study were
      healthy volunteers who had no confounding variables typically found in patients
      with schizophrenia. The cognitive function of healthy volunteers in response to
      single doses of haloperidol, risperidone, aripiprazole, and amisulpride in a
      double-blind placebo-controlled trial was investigated. Assessments for the
      computerized neurocognitive test, mental and physical sedation, and
      extrapyramidal symptoms were performed within 1 week before (baseline) and
      approximately 4 hours after drug administration. Compared to the placebo, single
      administration of amisulpride at 400 mg in healthy volunteers enhanced word
      fluency test performance and remained intact after controlling for sedation and
      extrapyramidal symptoms. Significant improvement in some measurements of the
      computerized neurocognitive test was also observed in each antipsychotic-treated
      group but may have been related to practice effect. These findings suggest that
      amisulpride may have cognitive-enhancing effects in healthy volunteers.

PMID- 23131891
TI  - Hypomania associated with adjunctive aripiprazole in an elder female with
      recurrent major depressive disorder: dose-related phenomenon?

PMID- 23131892
TI  - Acute laryngeal dystonia associated with aripiprazole.

PMID- 23131893
TI  - Atypical antipsychotics and pituitary tumors.

PMID- 23131894
TI  - Excessive insulin secretion in Japanese schizophrenic patients treated with
      antipsychotics despite normal fasting glucose levels.
AB  - The development of impaired glucose tolerance induced by antipsychotics (APs) is
      of concern as a serious adverse effect of psychiatric drug therapy. However, the
      mechanism by which APs cause dysfunction of the glucose-insulin response is not
      fully understood. Recent studies have shown that patients treated with APs for
      schizophrenia were more likely to exhibit impaired glucose tolerance after a
      glucose load compared with healthy control subjects, even if fasting glucose
      levels were within the reference range. To explain these findings, we
      hypothesized that insulin secretion is increased in schizophrenic patients
      treated with AP, even those normal fasting glucose (NFG) levels. Therefore, oral
      glucose tolerance tests were conducted in 159 Japanese inpatients with AP-treated
      schizophrenia and in 90 healthy subjects without schizophrenia. Plasma glucose
      and serum insulin concentrations were measured before (0 minute) and at 30, 60,
      90, and 120 minutes after the oral glucose load. Although insulin levels at 0
      minute were similar in both groups of subjects, insulin levels were significantly
      higher in the patients treated with AP at all times after the glucose load than
      in the healthy subjects. In analyses of NFG subjects, insulin levels were
      significantly higher in the patients treated with AP compared with the healthy
      subjects at all times after glucose loading. Overall, we found that insulin
      secretion in response to a glucose load was significantly higher in the patients
      treated with AP, irrespective of NFG. These results suggest that APs affect the
      glucose-insulin response, which may lead to subclinical insulin resistance before
      the onset of overt glucose intolerance.

PMID- 23131895
TI  - Institution animal care and use committees need greater ethical diversity.
AB  - In response to public outrage stemming from exposes of animal abuse in research
      laboratories, the US Congress in 1985 mandated Institutional Animal Care and Use
      Committees (IACUCs) to oversee animal use at institutions receiving federal
      grants. IACUCs were enjoined to respect public concern about the treatment of
      animals in research, but they were not specifically instructed whether or not to
      perform ethical cost-benefit analyses of animal research protocols that IACUCs
      have chosen, with approval contingent upon a balancing of animal pain and
      suffering against a reasonable expectation of resultant human benefit. IACUCs
      have chosen not to make such ethical judgments but, rather, restrict themselves
      to an advisory role, often tweaking the details of animal-use protocols, but
      eventually approving all of them. This disinclination by IACUCs to take a broader
      ethical view of their authority and responsibilities may reflect a membership
      composition highly skewed towards animal researchers themselves (67%) and
      institutional veterinarians (15%), both with vested interests in continuing
      animal research. The resultant ethical monoculture may impair IACUC's ability to
      meet public concern for laboratory animal welfare. Psychological research has
      established that unconscious bias affects us all, that deliberations among the
      like-minded lead to adapting extremist positions, and that groupthink blinds
      organisations to alternatives that might be obvious to outsiders. Taken together,
      skewed IACUC membership composition and psychological research insights into
      unconscious bias and groupthink suggest that an infusion of ethical diversity by
      increasing the percentage of institutionally unaffiliated members on IACUCs would
      broaden their ethical perspectives and enable them to better address public
      concerns about laboratory animal welfare.

PMID- 23131896
TI  - Suppression of CCR impacts metabolite profile and cell wall composition in Pinus
      radiata tracheary elements.
AB  - Suppression of the lignin-related gene cinnamoyl-CoA reductase (CCR) in the Pinus
      radiata tracheary element (TE) system impacted both the metabolite profile and
      the cell wall matrix in CCR-RNAi lines. UPLC-MS/MS-based metabolite profiling
      identified elevated levels of p-coumaroyl hexose, caffeic acid hexoside and
      ferulic acid hexoside in CCR-RNAi lines, indicating a redirection of metabolite
      flow within phenylpropanoid metabolism. Dilignols derived from coniferyl alcohol
      such as G(8-5)G, G(8-O-4)G and isodihydrodehydrodiconiferyl alcohol (IDDDC) were
      substantially depleted, providing evidence for CCR's involvement in coniferyl
      alcohol biosynthesis. Severe CCR suppression almost halved lignin content in TEs
      based on a depletion of both H-type and G-type lignin, providing evidence for
      CCR's involvement in the biosynthesis of both lignin types. 2D-NMR studies
      revealed minor changes in the H:G-ratio and consequently a largely unchanged
      interunit linkage distribution in the lignin polymer. However, unusual cell wall
      components including ferulate and unsaturated fatty acids were identified in TEs
      by thioacidolysis, pyrolysis-GC/MS and/or 2D-NMR in CCR-RNAi lines, providing new
      insights into the consequences of CCR suppression in pine. Interestingly, CCR
      suppression substantially promoted pyrolytic breakdown of cell wall
      polysaccharides, a phenotype most likely caused by the incorporation of acidic
      compounds into the cell wall matrix in CCR-RNAi lines.

PMID- 23131897
TI  - Clinical prognostic index for recurrence of papillary thyroid carcinoma including
      intraoperative findings.
AB  - This study created a new staging system using a risk model that employed clinical
      factors that were associated with recurrence, verified by preoperative clinical
      information and intraoperative finding and was compared with other staging
      systems. A review was conducted of patients who have undergone thyroidectomy and
      followed-up between January 1, 1983 and September 31, 2007 at Yonsei University
      Wonju Christian Hospital. The final prognostic staging system was defined as
      University of Yonsei clinical staging system (Prognostic score = 0.03 * Age + 0.8
      * (if male gender) + 0.5 * (if extrathyroidal tumor extension present) + 0.7 *
      (if clinically apparent lymph node metastasis present), Stage I, less than 1.50;
      Stage II, 1.50 to 2.29; Stage III, 2.30 to 3.29; Stage IV 4, 3.3 or more).
      Compared with the other staging systems, the proportion of variation explained
      (PVE %) was calculated for each. The University of Yonsei clinical staging system
      appeared to be first as an accurate prognosis predictor with 11.9%. New staging
      system can predict recurrence and has advantage can use preoperative clinical
      information and intraoperative finding. Those who are diagnosed as high risk
      patients using the new staging system should be treated with aggressive surgical
      treatment and close follow-up.

PMID- 23131898
TI  - Analysis of hepatic gene expression profile in a spontaneous mouse model of type
      2 diabetes under a high sucrose diet.
AB  - Both genetic factors and diabetogenic environmental factors, such as a high
      sucrose diet (HSD), are involved in the development of type 2 diabetes. In this
      study, the Nagoya-Shibata-Yasuda (NSY) mouse, an animal model of type 2 diabetes
      and C3H mice used as controls, were fed a HSD, a high-fat diet (HFD) or a regular
      diet (RD) from weaning. In C3H mice, HFD significantly increased body weight
      gain, but maintained glucose tolerance. In contrast, in NSY mice, HSD resulted in
      increased body weight gain and liver steatosis and increased glucose intolerance
      to a greater extent than HFD. Furthermore, we performed DNA microarray analysis
      to detect differences in hepatic gene expression levels in both strains under
      HSD. We then performed RT-PCR analysis on selected genes to evaluate basal
      expression level under RD and changes under HSD conditions. HSD-fed NSY, but not
      C3H mice, exhibited increased hepatic expression levels of Pparg2, an isoform of
      Pparg as well as G0s2, a target of Pparg, which are known to be adipocyte
      specific genes. Compared to RD-fed C3H mice, hepatic expression levels of Kat2b
      (transcriptional regulation), Hsd3b5 (steroid hormone metabolism) and Cyp7b1
      (bile acid metabolism) were initially lower in RD-fed NSY mice, and were further
      decreased in HSD-fed NSY mice. Expression of Metallothionein (Mt1) and
      Metallothionein 2 (Mt2) was significantly lower in NSY mice compared to C3H mice,
      irrespective of dietary condition. These data suggest that elucidation of this
      heterogeneity in response to HSD might contribute to further understanding of the
      gene-environment interactions leading to diabetes in humans.

PMID- 23131899
TI  - Elucidation of the O(1D) + HF -> F + OH mechanism by means of quasiclassical
      trajectories.
AB  - The dynamics and mechanism of the O((1)D) + HF -> F + OH reaction have been
      studied through quasi-classical trajectory calculations carried out on the 1(1)A'
      Potential Energy Surface (PES) fitted by Gomez-Carrasco et al. [Chem. Phys.
      Lett., 2007, 435, 188]. The influence of the collision energy and the initial
      rovibrational state on the reaction has been considered. As a result of this
      study, we conclude that for v = 0 the reactive collisions take place exclusively
      through an indirect mechanism that involves a long-lived complex. Interestingly
      and somewhat unexpectedly for a barrierless reaction, vibrational excitation
      causes a large enhancement of the reactivity due to the concurrence of a direct
      abstraction mechanism. Unlike other reactions also taking place on a barrierless
      PES featuring deep wells, no insertion mechanism is observed in O((1)D) + HF
      reactive collisions.

PMID- 23131901
TI  - A new insight into the initial step in the Fischer-Tropsch synthesis: CO
      dissociation on Ru surfaces.
AB  - In the present work, we have investigated the CO dissociation on corrugated
      Ru(1121) and the stepped Ru(0001) surfaces by means of density functional theory
      with slab models. Our results show that, while the direct CO dissociation is
      preferred on the six-fold site of Ru(1121), the H-assisted CO dissociation is
      found to be favored on the B5 site of the stepped Ru(0001) surface. Furthermore,
      we have studied the effects of co-adsorbed spectator species on the CO
      dissociation mechanisms. Our results demonstrate that spectators can change the
      potential energy landscape dramatically, such that different reaction mechanisms
      can be favored in the presence of different spectators. Neither the H-assisted CO
      dissociation mechanism nor the CO direct dissociation mechanism should be
      overlooked at authentic ambient conditions. This work emphasizes a dynamic
      picture of the reaction mechanisms due to the inherent structural and
      compositional inhomogeneity on surfaces. Different mechanisms can work together
      as different active sites will co-exist on a real catalyst surface, and the
      reaction preferences on an active site can vary as the adsorbate compositions on
      surfaces are varying during the course of the reactions.

PMID- 23131900
TI  - Imaging of anterior mediastinal tumours.
AB  - Anterior mediastinal tumours include primary and secondary tumours. Patients may
      be asymptomatic or present with symptoms related to local tumour invasion or
      systemic symptoms due to release of hormones/cytokines or antibodies. The most
      common symptoms at presentation include chest pain, dyspnoea, cough, fever and
      chills. Despite rapid developments in imaging techniques, accurate staging of
      anterior mediastinal tumours remains a diagnostic quandary. Multimodality imaging
      plays an important role in determining surgical resectability and/or impact on
      subsequent management. This article briefly discusses the epidemiology and
      incidence of anterior mediastinal tumours and describes the role of imaging in
      tumour characterization and staging in detail. We focus on the more commonly
      encountered anterior mediastinal tumours.

PMID- 23131902
TI  - [Cherubism: a case followed for 18 years].
AB  - Cherubism is a rare and benign bone disease affecting the bones of the face,
      mainly the mandible, sometimes the maxilla and exceptionally the whole skeleton.
      The physiopathology is briefly mentioned, especially the genetic aspect of the
      disease. Subsequently, we present the case of a patient suffering from cherubism,
      a case we have been following from the age of four and a half to the age of 22.
      Each step of the surgical treatment is illustrated through a wide iconography.
      The discussion analyses the intellectual process that leads to diagnosis. The
      clinical examination is fundamental, as well as the radiological check-up but the
      latter may not be feasible due to the young age of the patient. The definite
      diagnosis relies on the histological examination of the bone concerned. It will
      show an association of dense, abundant and highly vascularised conjunctive tissue
      together with giant plurinuclear cells, without any mitosis nor any cellular
      atypia. The other bone diseases affecting the bones of the face will have to be
      sought, of course, and eliminated through the clinical and radiological
      examinations and, above all, by the histological examination which is the basis
      of the definite diagnosis. The treatment of cherubism is still a controversial
      issue: some authors are in favour of therapeutic abstention while others support
      the recourse to surgery to deal with the functional and aesthetic dimensions of
      the disease. In conclusion, the authors insist that the diagnosis of cherubism is
      apparently easy. Cherubism must be envisaged in the case of a chubby-cheeked
      child and a sample of pathological bone should be taken in order to ascertain the
      diagnosis.

PMID- 23131903
TI  - Treating a collagen scaffold with a low concentration of nicotine-promoted
      angiogenesis and wound healing.

PMID- 23131905
TI  - Interpreting a helping hand: cultural variation in the effectiveness of solicited
      and unsolicited social support.
AB  - Research has shown that Asians/Asian Americans are less likely to seek social
      support to deal with stressful situations than European Americans. Two studies
      examined the effectiveness of two types of social support: support that is sought
      directly (solicited support) and support received without prompting from the
      recipient (unsolicited support). It was theorized that receiving unsolicited
      support may reinforce social belonging and relational ties, whereas soliciting
      support may pose relational threats for Asian Americans. In contrast, European
      Americans may be less affected by type of support received. The first study
      examined culture (European American vs. Asian American) and type of social
      support (solicited vs. unsolicited) on stress responses to a task in a lab
      setting. The second study used vignettes of possible stressors with unsolicited
      or solicited coping techniques. Results supported our hypothesis, with Asian
      Americans reporting better outcomes from unsolicited support and European
      Americans showing little difference between support types.

PMID- 23131906
TI  - Blinding trust: the effect of perceived group victimhood on intergroup trust.
AB  - Four studies investigate how perceptions that one's social group has been
      victimized in society-that is, perceived group victimhood (PGV)-influence
      intergroup trust. Jewish and politically conservative participants played an
      economic trust game ostensibly with "partners" from their ingroup and/or a
      salient outgroup. Across studies, participants dispositionally or primed to be
      high in PGV revealed greater trust behavior with ingroup than outgroup partners.
      Control participants and those dispositionally low in PGV did not display such
      bias. Study 3 revealed, moreover, that high PGV enhanced ingroup trust even after
      an overt betrayal by an ingroup partner. Results were not explained by
      fluctuations in group identification, highlighting the novel, independent role of
      PGV in shaping an important aspect of intergroup relations-that is, trust.
      Implications of PGV for intergroup relations are discussed.

PMID- 23131907
TI  - Women's mental health: Unwanted pregnancy.

PMID- 23131904
TI  - The prevalence of BRCA mutations among familial breast cancer patients in Korea:
      results of the Korean Hereditary Breast Cancer study.
AB  - The primary aim of this study was to estimate the prevalence of BRCA1/2 mutations
      among familial breast cancer (BC) patients in Korea. We analyzed 775 familial BC
      patients who were enrolled in the Korean Hereditary Breast Cancer (KOHBRA) study
      and treated at 36 institutions between May 2007 and May 2010. Patients with
      familial BC were defined as BC patients with family histories of BC or ovarian
      cancer (OC) in any relatives. All probands received genetic counseling and BRCA
      genetic testing was performed after obtaining informed consent. The mean age of
      BC diagnosis was 43.6 years. The numbers of probands with family histories of BC
      only and OC only were 682 and 93, respectively. The overall prevalence of the
      BRCA mutation among familial BC patients was 21.7 % (BRCA1 9.3 % and BRCA2 12.4
      %). Subgroup analyses observed prevalences of the BRCA mutation as follows: 19.6
      % among patients with BC family history only (BRCA1 7.6 % and BRCA2 12.0 %) and
      36.6 % among patients with OC family history only (BRCA1 21.5 % and BRCA2 15.1
      %). Most of the subgroups satisfied the 10 % probability criteria to undergo BRCA
      testing. However, the prevalence of the BRCA mutations among subgroups that had 2
      BC patients in a family with both age at diagnosis of more than 50 years old did
      not reach the 10 % criteria (4.1 %). Korean familial BC patients are good
      candidates for BRCA testing even when they have family histories of single breast
      cancers. However, proband age at diagnosis should be carefully considered when
      selecting patients for testing.

PMID- 23131908
TI  - Zirconium and hafnium complexes based on 2-aryl-8-arylaminoquinoline ligands:
      synthesis, molecular structure, and catalytic performance in ethylene
      copolymerization.
AB  - A general and efficient approach toward new zirconium and hafnium complexes based
      on 2-aryl-8-arylaminoquinoline ligands was developed. These precursors, when
      activated with MAO/borate cocatalyst and supported on silica, result in active
      olefin polymerization catalysts. The ethylene copolymers produced under
      industrially relevant conditions show very high molecular weights and unique
      microstructures defined by the multisite nature of the catalyst. A site
      diversification mechanism is proposed to explain the presence of at least five
      individual sites, as deduced from 3D-TREF analysis of ethylene-butene copolymers.

PMID- 23131910
TI  - Reducing avoidable pressure ulcers: an online clinical ordering system.
AB  - Healthcare practitioners face diverse challenges presented by an ageing
      population, reducing funds, public demand for better health care, and a zero
      tolerance to avoidable healthcare-acquired injuries, such as pressure ulcers. To
      support the reduction in avoidable pressure ulcers European Pressure Ulcer
      Advisory Panel and National Institute for Health and Clinical Excellence
      guidelines recommend patient repositioning, the provision of either an active or
      reactive pressure-redistributing support surface and, for some, complete and
      permanent off-loading of the tissue. Guy's and St. Thomas's NHS Foundation Trust
      recognised that an evidence-based prevention strategy was required to reduce the
      incidence of pressure ulcers in line with the Harm Free Care initiative. As part
      of the prevention strategy, eTRACE was implemented, an online clinical ordering
      system that uses the patient's clinical risk assessment in conjunction with the
      Trust's clinical protocols to recommend appropriate equipment selection.
      Additionally the system supports the organisational and national
      reporting/management requirements. This article will review the clinical and
      economic evidence to support the introduction of eTRACE and how this system has
      contributed to the Trust's agenda in reducing avoidable pressure ulcers.

PMID- 23131909
TI  - The value of nurse-led tissue viability services.

PMID- 23131911
TI  - A randomised trial of honey barrier cream versus zinc oxide ointment.
AB  - In this single-blind multicentre, intervention study, 31 patients with
      symmetrical intertrigo in large skin folds were included to study the clinical
      effect of two topical treatments, i.e. standard therapy with zinc oxide ointment
      versus honey barrier cream. Patients were treated twice daily for 21 days, and
      the severity of intertrigo was scored in an observation period of 21 days.
      Patients were used as their own controls by treating symmetrical skin folds, on
      the left and right side. There was no significant difference in treatment effect
      between intervention groups. For the majority of patients, both treatments were
      effective. However, the use of honey barrier cream showed lower pruritus
      complaints (12.9% versus 29.0%). Honey barrier cream is a suitable alternative in
      the treatment of intertrigo, and promotes patient comfort.

PMID- 23131912
TI  - Super-absorbent dressings: how do they perform in vitro?
AB  - The free swell and absorption capacity under compression of six wound dressings
      that are indicated for moderately to highly exuding wounds was investigated.
      Measuring in vitro the absorptive capacity and retention under compression is
      important in terms of clinical efficacy and efficiency. This in vitro comparative
      study demonstrated that sorbion sachet EXTRA had the highest free swell capacity
      of the six test dressings and absorbed more than twice the volume (126%) of the
      test solution than its nearest competitor. When measuring capacity under
      compression, sorbion sachet EXTRA absorbed 88% more fluid than the nearest
      competitor.

PMID- 23131913
TI  - Painful dressing changes for chronic wounds: assessment and management.
AB  - Wound pain can arise from the wound itself, continuing wound treatment and
      anticipatory pain, which occurs in some patients as a consequence of negative
      experiences of care. Specifically, pain caused by the removal and application of
      dressings has been identified as a major contributor to wound pain, from both
      patient and health professional perspectives. This article reviews literature on
      the impact of pain at dressing change, and provides practical suggestions for
      assessment and management of pain during wound care.

PMID- 23131914
TI  - Negative pressure wound therapy and the government agenda.

PMID- 23131915
TI  - Wound healing: the evidence  for hyperbaric oxygen therapy.
AB  - This article reviews evidence for the promotion of healing using hyperbaric
      oxygen therapy (HBOT). HBOT is an adjuvant wound therapy that has been suggested
      to be beneficial for the healing of wounds for over 40 years. Current approved
      treatments provide 100% oxygen to a patient who is in a multi-place compression
      chamber accompanied inside the chamber by a trained attendant. Its ability to
      increase the arterial partial pressure of oxygen in the human body and facilitate
      oxygen transport when the body's oxygen transport system has been compromised
      makes it appropriate for a number of indications. Oxygen is essential for normal
      wound healing and contributes to a number of processes required for a healing
      wound. HBOT is an additional therapy and lacks the capacity to heal wounds
      without the application of approved wound care practice. Animal studies and
      clinical trials have demonstrated the benefits of HBOT on the hypovascular
      hypocellular-hypoxic environment of a chronic wound when the wound has not
      responded to other treatments. Evidence suggests that the addition of HBOT is
      effective in the healing of diabetic foot ulcers but that presently this benefit
      is not evident at long-term follow up.

PMID- 23131916
TI  - Topographical anatomy of superficial veins, cutaneous nerves, and arteries at
      venipuncture sites in the cubital fossa.
AB  - We investigated correlations among the superficial veins, cutaneous nerves,
      arteries, and venous valves in 128 cadaveric arms in order to choose safe
      venipuncture sites in the cubital fossa. The running patterns of the superficial
      veins were classified into four types (I-IV) and two subtypes (a and b). In types
      I and II, the median cubital vein (MCV) was connected obliquely between the
      cephalic and basilic veins in an N-shape, while the median antebrachial vein
      (MAV) opened into the MCV in type I and into the basilic vein in type II. In type
      III, the MCV did not exist. In type IV, additional superficial veins above the
      cephalic and basilic veins were developed around the cubital fossa. In types Ib
      IVb, the accessory cephalic vein was developed under the same conditions as seen
      in types Ia-IVa, respectively. The lateral cutaneous nerve of the forearm
      descended deeply along the cephalic vein in 124 cases (97 %), while the medial
      cutaneous nerve of the forearm descended superficially along the basilic vein in
      94 (73 %). A superficial brachial artery was found in 27 cases (21 %) and passed
      deeply under the ulnar side of the MCV. A median superficial antebrachial artery
      was found in 1 case (1 %), which passed deeply under the ulnar side of the MCV
      and ran along the MAV. Venous valves were found at 239 points in 28 cases with
      superficial veins, with a single valve seen at 79 points (33 %) and double valves
      at 160 points (67 %). At the time of intravenous injection, caution is needed
      regarding the locations of cutaneous nerves, brachial and superficial brachial
      arteries, and venous valves. The area ranging from the middle segment of the MCV
      to the confluence between the MCV and cephalic vein appears to be a relatively
      safe venipuncture site.

PMID- 23131919
TI  - Setting Snail2's pace during EMT.
AB  - Epithelial to mesenchymal transition (EMT) is a fundamental process in both
      development and cancer progression. The transcription factor Elf5 is now reported
      as an upstream regulator of the key EMT inducer Snail2, and is shown to regulate
      the earliest known rewiring events required for tumour cell invasiveness and
      metastasis.

PMID- 23131920
TI  - The amorphous pericentriolar cloud takes shape.
AB  - The pericentriolar material (PCM), the microtubule-organizing component of the
      centrosome, contains a multitude of proteins and is commonly described as an
      amorphous cloud surrounding the centrioles. However, the days of the PCM as an
      unstructured matrix are numbered. Using super-resolution microscopy, several
      reports have now revealed remarkable domain organization within the PCM.

PMID- 23131918
TI  - The functions of microRNAs in pluripotency and reprogramming.
AB  - Pluripotent stem cells (PSCs) express a distinctive set of microRNAs (miRNAs).
      Many of these miRNAs have similar targeting sequences and are predicted to
      regulate downstream targets cooperatively. These enriched miRNAs are involved in
      the regulation of the unique PSC cell cycle, and there is increasing evidence
      that they also influence other important characteristics of PSCs, including their
      morphology, epigenetic profile and resistance to apoptosis. Detailed studies of
      miRNAs and their targets in PSCs should help to parse the regulatory networks
      that underlie developmental processes and cellular reprogramming.

PMID- 23131927
TI  - Monitoring immunosuppressive medications for lung disease and lung
      transplantation: the time is now.

PMID- 23131928
TI  - A step forward in COPD management: reading between the lines.

PMID- 23131929
TI  - Improving asthma management: time for an action plan.

PMID- 23131930
TI  - Out-of-proportion pulmonary hypertension: a paradigm for rare diseases.

PMID- 23131932
TI  - Point: should all ICU patients receive continuous sedation? Yes.

PMID- 23131933
TI  - Counterpoint: should all ICU patients receive continuous sedation? No.

PMID- 23131936
TI  - Executive summary: monitoring of nonsteroidal immunosuppressive drugs in patients
      with lung disease and lung transplant recipients: American College of Chest
      Physicians evidence-based clinical practice guidelines.

PMID- 23131938
TI  - Novel antiinflammatory therapies for COPD.
AB  - The biologic nature of COPD inflammation is not well understood and agents that
      inhibit inflammation in COPD are a major unmet need. However, a variety of agents
      that have the potential to be inhibitors of COPD inflammation are in various
      stages of development. Agents that have been approved for a non-COPD indication
      but that have potential for inhibiting COPD inflammation include the statins,
      some phosphodiesterase inhibitors, some long-acting beta agonists, tiotropium
      bromide, the peroxisome proliferator-activated receptor-gamma agonist
      rosiglitazone, and various monoclonal antibodies. New molecular entities that are
      being developed specifically as antiinflammatory agents for COPD include a
      variety of chemokine receptor antagonists, inhibitors of matrix
      metalloproteinases, inhibitors of p38 mitogen-activated protein kinases, and stem
      cells. Some other novel agents that are in preclinical or early clinical stages
      are mentioned.

PMID- 23131937
TI  - The emerging importance of autophagy in pulmonary diseases.
AB  - Important cellular processes such as inflammation, apoptosis, differentiation,
      and proliferation confer critical roles in the pathogenesis of human diseases. In
      the past decade, an emerging process named "autophagy" has generated intense
      interest in both biomedical research and clinical medicine. Autophagy is a
      regulated cellular pathway for the turnover of organelles and proteins by
      lysosomal-dependent processing. Although autophagy was once considered a bulk
      degradation event, research shows that autophagy selectively degrades specific
      proteins, organelles, and invading bacteria, a process termed "selective
      autophagy." It is increasingly clear that autophagy is directly relevant to
      clinical disease, including pulmonary disease. This review outlines the principal
      components of the autophagic process and discusses the importance of autophagy
      and autophagic proteins in pulmonary diseases from COPD, alpha1-antitrypsin
      deficiency, pulmonary hypertension, acute lung injury, and cystic fibrosis to
      respiratory infection and sepsis. Finally, we examine the dual nature of
      autophagy in the lung, which has both protective and deleterious effects
      resulting from adaptive and maladaptive responses, and the challenge this duality
      poses for designing autophagy-based diagnostic and therapeutic targets in lung
      disease.

PMID- 23131940
TI  - Immunohistochemistry: applications to the evaluation of lung and pleural
      neoplasms: part 1.
AB  - Immunohistochemistry has come to occupy a key position among the armamentarium of
      tools pathologists apply to the evaluation of lung and pleural neoplasms. This
      technique uses antibodies that bind to specific antigens, usually proteins,
      enabling microscopic detection of the antigens. Over the last several decades, an
      impressive array of antibodies has become commercially available, and many of
      these antibodies have become integrated into the routine practice of pathology.
      Evaluation of tissue or cytology samples with these antibodies can facilitate
      determination of tumor type and site of origin. Comments citing results of
      immunohistochemical staining with these antibodies frequently appear in pathology
      reports and may be difficult to translate for those less familiar with the
      technique. This review presents, in two parts, common diagnostic applications of
      immunohistochemistry, with information about strategies taken for frequently
      encountered differential diagnostic scenarios. This, the first of two parts,
      offers a basic overview of the technique and discusses its applications in the
      diagnosis of common primary lung carcinomas.

PMID- 23131939
TI  - Household air pollution is a major avoidable risk factor for cardiorespiratory
      disease.
AB  - Household air pollution (HAP) from biomass fuels, coal, and kerosene burned in
      open fires, primitive stoves, and lamps causes at least 2 million deaths per
      year. Many of these deaths occur in children <5 years of age with pneumonia and
      in women with COPD, lung cancer, and cardiovascular disease. HAP is inextricably
      linked to poverty, with activities to obtain fuel consuming a large proportion of
      the time and financial resources of poor households. Thus, fewer resources used
      in this way means less is available for basic needs like food, education, and
      health care. The burden of work and the exposure to smoke, particularly during
      cooking, are predominantly borne by women and children. Although historically HAP
      has not received sufficient attention from the scientific, medical, public
      health, development, and policy-making communities, the tide has clearly changed
      with the broad-based support and launch of the Global Alliance for Clean
      Cookstoves in 2010. There is now considerable reason for optimism that this
      substantial cause of cardiorespiratory morbidity and mortality will be addressed
      comprehensively and definitively. Drawing on our experience from four continents,
      we provide background information on the problem of HAP, health impacts of HAP,
      opportunities for research, and the current best solutions.

PMID- 23131941
TI  - Immunohistochemistry: applications to the evaluation of lung and pleural
      neoplasms: part 2.
AB  - Immunohistochemistry has come to occupy a key position among the armamentarium of
      tools pathologists apply to the evaluation of lung and pleural neoplasms. This
      technique uses antibodies that bind to specific antigens, usually proteins,
      enabling microscopic detection of the antigens. Over the last several decades, an
      impressive array of antibodies has become commercially available, and many of
      these antibodies have become integrated into the routine practice of pathology.
      Evaluation of tissue or cytology samples with these antibodies can facilitate
      determination of tumor type and site of origin. Comments citing results of
      immunohistochemical staining with these antibodies frequently appear in pathology
      reports and may be difficult to translate for those less familiar with the
      technique. This review presents, in two parts, common diagnostic applications of
      immunohistochemistry with information about strategies taken for frequently
      encountered differential diagnostic scenarios. This article is the second of the
      two parts and focuses on immunohistochemical approaches to differentiating
      primary pulmonary from metastatic adenocarcinomas, mesotheliomas from carcinomas,
      and various types of spindle cell neoplasms. Potential future directions
      involving therapeutic and prognostic biomarkers are also discussed.

PMID- 23131942
TI  - The expanding horizons of endobronchial ultrasound: diagnosis of a tumor
      embolism.
AB  - A 51-year-old woman was given a diagnosis of primary retroperitoneal synovial
      sarcoma, which was surgically removed, and she was subsequently treated with
      chemotherapy and radiotherapy. Five years later, the patient was readmitted with
      a 1-month history of progressive dyspnea and was initially given a diagnosis of
      bilateral pulmonary embolism. Angiography performed some time later revealed
      progression of the previous filling defects and the appearance of two new nodular
      endovascular images. Endobronchial ultrasound-guided transbronchial needle
      aspiration (EBUS-TBNA) was performed, and the cytologic analysis of the cell
      aspirate was compatible with endovascular metastatic sarcoma. In conclusion, EBUS
      TBNA in the appropriate setting is an effective method for sampling endovascular
      lesions, adding pathologic information and allowing for early and accurate
      diagnosis.

PMID- 23131943
TI  - Recurrent pneumonia, persistent cough, and dyspnea in a 41-year-old man.

PMID- 23131944
TI  - A 61-year-old man with dyspnea.

PMID- 23131945
TI  - Patient with fever, hypoxemia, and pulmonary consolidations.

PMID- 23131950
TI  - FVC, total lung capacity, and the differential association to mortality.

PMID- 23131952
TI  - Endobronchial ultrasound-guided biopsy of mediastinal and hilar lymph nodes: a
      word on false positives.

PMID- 23131955
TI  - Pleural manometry: our point of view.

PMID- 23131957
TI  - Does cuff material and design help prevent ventilator-associated pneumonia?

PMID- 23131959
TI  - Development and efficacy of a 1-d thoracic ultrasound training course.

PMID- 23131962
TI  - Involving patients in their healthcare.

PMID- 23131963
TI  - Arterial stiffness using cardio-ankle vascular index reflects cerebral small
      vessel disease in healthy young and middle aged subjects.
AB  - AIM: The cardio-ankle vascular index (CAVI) reflects overall arterial stiffness
      from the aorta to the ankle, independent of blood pressure. Cerebral small vessel
      diseases (SVDs), including white matter lesions (WML), silent lacunar infarction
      (SLI) and cerebral microbleeds (CMB), are considered to increase the risk of
      stroke and cognitive impairment further. We aimed to investigate the association
      of cerebral SVD with CAVI in asymptomatic young and middle-aged subjects.
      METHODS: Asymptomatic Korean individuals aged 30 to 59 years old without
      neurologic disease who had CAVI and brain magnetic resonance imaging (MRI) were
      evaluated retrospectively. RESULTS: Among 484 subjects, cerebral SVDs (advanced
      WML, SLI and CMB) were found in 20 (4.1%). Subjects with SVDs tended to be older
      and to have higher systolic blood pressure (SBP) and higher CAVI. From
      multivariate regression analysis, including pulse pressure (PP) or SBP, CAVI
      showed a significant association with SVD [adjusted OR (95% CI): 1.889 (1.094
      3.263), p= 0.002 and 1.793 (1.020-3.153), p= 0.043, for PP and SBP,
      respectively]. When CAVI was assessed by quartiles, the highest quartile of CAVI
      (CAVI >7.65) showed a significant association with SVD, after adjustment for PP
      [adjusted OR (95% CI): 2.766 (1.115-6.866), p= 0.028]. CONCLUSION: In young and
      middle-aged subjects, cerebral SVD was significantly associated with arterial
      stiffness measured by CAVI after adjusting for PP or SBP.

PMID- 23131964
TI  - Well-defined lipid interfaces for protein adsorption studies.
AB  - The biomolecule-artificial lipid membrane interface has been investigated by QCM
      D, SPR, and FRAP techniques, to study the adsorption process of ferritin on
      supported lipid bilayers (SLBs) of different composition and charge. Results
      point out to the predominant role of electrostatics in triggering the interaction
      of ferritin with SLBs.

PMID- 23131965
TI  - Disability Rating Scale.

PMID- 23131966
TI  - Insomnia, fatigue, and sleepiness in the first 2 years after traumatic brain
      injury: an NIDRR TBI model system module study.
AB  - OBJECTIVE: To determine the prevalence of insomnia and posttraumatic brain injury
      (TBI) fatigue (PTBIF) in individuals with moderate to severe TBI, to explore the
      relationship between PTBIF and insomnia and their association with outcomes.
      DESIGN: Cross-sectional study. SETTING: Five National Institute of Disability and
      Rehabilitation Research TBI Model Systems. PARTICIPANTS: Three hundred thirty
      four individuals with TBI who completed 1-year (n = 213) or 2-year (n = 121)
      follow-up interviews between 2008 and 2012. MAIN OUTCOME RESULTS: Insomnia
      occurred in 11% to 24% and PTBIF in 33% to 44% of the individuals. Insomnia and
      fatigue were both related to sleep disturbance, sleep hygiene, satisfaction with
      life, anxiety, and depression. PTBIF was associated with greater disability and
      sleepiness. Insomnia without fatigue was rare (2%-3%) but PTBIF without insomnia
      occurred in 21% to 23% of the individuals. Comorbidity occurred in 9% to 22% of
      the individuals. CONCLUSIONS: Although PTBIF and insomnia are closely related and
      both associated with poorer quality of life, they are affected independently by a
      variety of factors, especially psychopathology and sleep quality. A majority of
      individuals with PTBIF do not have insomnia; and PTBIF appears to be related to
      disability severity and daytime sleepiness, where insomnia is not. Demographic
      and injury variables are not strong predictors of insomnia or PTBIF.

PMID- 23131967
TI  - Extension of the representativeness of the Traumatic Brain Injury Model Systems
      National Database: 2001 to 2010.
AB  - OBJECTIVE: To extend the representativeness of the Traumatic Brain Injury Model
      Systems National Database (TBIMS-NDB) for individuals 16 years and older,
      admitted for acute, inpatient rehabilitation in the United States with a primary
      diagnosis of traumatic brain injury (TBI) analyses completed by Corrigan and
      colleagues by comparing this data set to national data for patients admitted to
      inpatient rehabilitation with identical inclusion criteria that included 3
      additional years of data and 2 new demographic variables. DESIGN: Secondary
      analysis of existing data sets and extension of previously published analyses.
      SETTING: Acute inpatient rehabilitation facilities. PARTICIPANTS: Patients 16
      years and older with a primary rehabilitation diagnosis of TBI; the US TBI
      Rehabilitation population, n = 156 447; and the TBIMS-NDB population, n = 7373.
      INTERVENTIONS: None. MAIN OUTCOME MEASURES: Demographics, functional status, and
      length of stay in hospital. RESULTS: The TBIMS-NDB was largely representative of
      patients 16 years and older, admitted for rehabilitation in the United States
      with a primary diagnosis of TBI on or after October 1, 2001, and discharged as of
      December 31, 2010. The results of the extended analyses were similar to those
      reported by Corrigan and colleagues. Age accounted for the largest difference
      between the samples, with the TBIMS-NDB including a smaller proportion of
      patients 65 years and older than all those admitted for rehabilitation with a
      primary diagnosis of TBI in the United States. After partitioning each data set
      at age 65, most distributional differences found between samples were markedly
      reduced; however, differences in the preinjury vocational status of the employed
      and rehabilitation lengths of stay between 1 and 9 days remained robust. The
      subsamples of patients 64 years and younger were found to differ only slightly on
      all remaining variables, whereas those 65 years and older were found to have
      meaningful differences in insurance type and age distribution. CONCLUSIONS: These
      results reconfirm that the TBIMS-NDB is largely representative of patients with
      TBI receiving inpatient rehabilitation in the United States. Differences between
      the 2 data sets were found to be stable across the 3 additional years of data,
      and new differences were limited to those involving newly introduced variables.
      To use these data for population-based research, it is strongly recommended that
      statistical adjustment be conducted to account for the lower percentage of
      patients older than 65 years, inpatient rehabilitation stays less than 10 days,
      and preinjury vocational status in the TBIMS-NDB.

PMID- 23131968
TI  - Psychometric properties of the Multidimensional Assessment of Fatigue scale in
      traumatic brain injury: an NIDRR Traumatic Brain Injury Model Systems study.
AB  - OBJECTIVE: To investigate the psychometric properties of the Multidimensional
      Assessment of Fatigue (MAF) scale in a traumatic brain injury (TBI) sample.
      DESIGN: Prospective survey study. SETTING: Community. PARTICIPANTS: One hundred
      sixty-seven individuals with TBI admitted for inpatient rehabilitation, enrolled
      into the TBI Model Systems national database, and followed up at either the first
      or second year postinjury. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURE(S): Multidimensional Assessment of Fatigue. RESULTS: The initial
      analysis, using items 1 to 14, which are based on a 10-point rating scale, found
      that only 1 item ("walking") misfit the overall construct of fatigue in this TBI
      population. However, this 10-point rating scale was found to have disordered
      thresholds. When ratings were collapsed into 4 response categories, all MAF items
      used to calculate the Global Fatigue Index formed a unidimensional scale.
      CONCLUSION(S): Findings generally support the unidimensionality of the MAF when
      used in a TBI population but call into question the use of a 10-point rating
      scale for items 1 to 14. Further study is needed to investigate the use of a 4
      category rating scale across all items and the fit of the "walking" item for a
      measure of fatigue among individuals with TBI.

PMID- 23131969
TI  - Traumatic brain injury with and without late posttraumatic seizures: what are the
      impacts in the post-acute phase: a NIDRR Traumatic Brain Injury Model Systems
      study.
AB  - OBJECTIVE: To compare and contrast the levels of impairment, disability, and
      community participation of individuals with traumatic brain injury (TBI) with or
      without late posttraumatic seizures (LPTS). DESIGN: Prospective survey study.
      SETTING: Community. PARTICIPANTS: Two groups of 91 individuals with TBI, with and
      without LPTS, were enrolled in the TBI Model Systems National Database between
      1989 and 2002 and interviewed at years 1, 2, and 5 postinjury. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Demographic, injury severity, productivity,
      and psychosocial outcomes. RESULTS: The majority of the demographic and
      productivity outcomes up to 5 years postinjury were similar between individuals
      in the LPTS and non-LPTS groups. Both the LPTS and non-LPTS groups showed an
      increasing percentage of individuals who began to live alone after the first year
      postinjury and a decreasing percentage of individuals who were living with family
      members at 5 years postinjury compared with the first year post-TBI. A higher
      percentage of individuals in the LPTS group reported using more dependent forms
      of transportation such as riding with others or using public transportation.
      Individuals in the LPTS group had higher Disability Rating Scale scores at all
      time points, denoting greater functional disability, than individuals in the non
      LPTS group, despite the 2 groups having similar Disability Rating Scale scores at
      discharge from rehabilitation. Satisfaction With Life Scale scores showed no
      changes over time but were significantly different between both groups at all
      time points, with individuals in the LPTS group reporting lower Satisfaction With
      Life Scale score than individuals in the non-LPTS group. CONCLUSIONS: It does
      appear that the development of LPTS following a TBI is associated with poorer
      functional and psychosocial outcomes in the first 5 years after injury. It
      remains to be determined whether there are other factors that also may account
      for these differences and that may be amenable to intervention.

PMID- 23131970
TI  - Mortality after surviving traumatic brain injury:  risks based on age groups.
AB  - OBJECTIVE: To assess mortality, life expectancy, risk factors, and causes of
      death by age groups among persons who received inpatient traumatic brain injury
      (TBI) rehabilitation. DESIGN: Prospective cohort study. SETTING: The TBI Model
      Systems. PARTICIPANTS: 8573 individuals injured between 1988 and 2009, with
      survival status per December 31, 2009, determined. INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: Standardized mortality ratio, life expectancy, and cause
      of death. RESULTS: Moderate-severe TBI increases risk of mortality compared with
      the general population in all age groups, with the exception of those 85 years or
      older at the time of injury. Teenagers to middle-aged adults are at particular
      risk. Risk factors for death varied by age group and included gender, marital and
      employment status, year and cause of injury, and level of disability. External
      causes of death predominate in younger groups. For the youngest male participants
      in the sample, longevity was reduced up to 16 years. CONCLUSION: Risk factors and
      causes of death varied considerably by age group for individuals with moderate
      severe TBI who were receiving acute care rehabilitation. Moderate-severe TBI is a
      chronic health condition.

PMID- 23131971
TI  - A health and wellness intervention for those with moderate to severe traumatic
      brain injury:  a randomized controlled trial.
AB  - OBJECTIVES: To assess the efficacy of a standardized 12-week health and wellness
      group intervention for those with moderate to severe traumatic brain injury
      (TBI). STUDY DESIGN: Randomized controlled trial. PARTICIPANTS: Seventy-four
      individuals with moderate to severe TBI recruited from the outpatient program at
      a rehabilitation hospital, a Veterans Affairs Medical Center, and the community.
      METHOD: Eligible participants were randomized to treatment (health and wellness
      therapy group) or wait-list control (treatment, n = 37; wait-list, n = 37). The
      primary outcome was the Health Promoting Lifestyle Profile-II. RESULTS: The
      results of the mixed-model repeated-measures analysis indicated no differences
      between treatment and control groups engaging in activities to increase their
      health and well-being. CONCLUSIONS: Findings did not support the efficacy of the
      intervention. Results may have been impacted by the wide variability of
      individualized health and wellness goals selected by group members, the structure
      and/or content of the group, and/or the outcome measures selected.

PMID- 23131972
TI  - Life expectancy following rehabilitation: a NIDRR Traumatic Brain Injury Model
      Systems study.
AB  - OBJECTIVE: To characterize overall and cause-specific mortality and life
      expectancy among persons who have completed inpatient traumatic brain injury
      rehabilitation and to assess risk factors for mortality. DESIGN: Prospective
      cohort study. SETTING: The Traumatic Brain Injury Model Systems. PARTICIPANTS: A
      total of 8573 individuals injured between 1988 and 2009, with survival status per
      December 31, 2009, determined. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: Standardized mortality ratio (SMR), life expectancy, cause of death.
      RESULTS: SMR was 2.25 overall and was significantly elevated for all age groups,
      both sexes, all race/ethnic groups (except Native Americans), and all injury
      severity groups. SMR decreased as survival time increased but remained elevated
      even after 10 years postinjury. SMR was elevated for all cause-of-death
      categories but especially so for seizures, aspiration pneumonia, sepsis,
      accidental poisonings, and falls. Life expectancy was shortened an average of 6.7
      years. Multivariate Cox regression showed age at injury, sex, race/ethnic group,
      marital status and employment status at the time of injury year of injury,
      preinjury drug use, days unconscious, functional independence and disability on
      rehabilitation discharge, and comorbid spinal cord injury to be independent risk
      factors for death. CONCLUSION: There is an increased risk of death after moderate
      or severe traumatic brain injury. Risk factors and causes of death have been
      identified that may be amenable to intervention.

PMID- 23131974
TI  - Dipole moments of isomeric alkoxyalcohols in cyclohexane. Comparison of
      Hedestrand and Frohlich procedures with a new formula.
AB  - Limiting dipole moments of four isomeric alkoxyalcohols dissolved in cyclohexane
      at 298.15 K were determined from measurements of the relative permittivity of at
      least 17 dilute solutions up to solute mole fraction of 0.03. In addition, 5 to 7
      data points were obtained up to a mole fraction of 0.1. A stepwise dilution
      device ensured dielectric measurements to be performed in highly dilute solutions
      with accurately determined concentrations. Densities of these solutions and
      refractive indices of the pure liquids were independently measured. Limiting
      dipole moments were calculated using Hedestrand's equation and an improved method
      of implementing Frohlich's equation, which circumvents extrapolation difficulties
      referred to in the literature. A new formula, based on the one-liquid approach
      for extending the Onsager-Kirkwood-Frohlich equation to liquid mixtures, is
      introduced and shown to yield a reliable and robust procedure for estimating
      dipole moments of polar molecules dissolved in non-polar solvents. Limiting
      dipole moment values for 2-tert-butoxyethanol (2.31 D), 1-propoxypropan-2-ol
      (2.14 D), 2-butoxyethanol (2.14 D) and 2-isobutoxyethanol (2.08 D) are
      recommended. The relative order of these values appears to determine the order of
      hydrophilicity of these four alkoxyalcohols as suggested by their recently
      reported limiting partial molar volumes and isentropic compressions in aqueous
      solutions.

PMID- 23131973
TI  - Neurocognitive predictors of financial capacity in traumatic brain injury.
AB  - OBJECTIVE: To develop cognitive models of financial capacity (FC) in patients
      with traumatic brain injury (TBI). DESIGN: Longitudinal design. SETTING:
      Inpatient brain injury rehabilitation unit. PARTICIPANTS: Twenty healthy
      controls, and 24 adults with moderate-to-severe TBI were assessed at baseline (30
      days postinjury) and 6 months postinjury. MAIN OUTCOME MEASURES: The FC
      instrument (FCI) and a neuropsychological test battery. Univariate correlation
      and multiple regression procedures were employed to develop cognitive models of
      FCI performance in the TBI group, at baseline and 6-month time follow-up.
      RESULTS: Three cognitive predictor models of FC were developed. At baseline,
      measures of mental arithmetic/working memory and immediate verbal memory
      predicted baseline FCI performance (R = 0.72). At 6-month follow-up, measures of
      executive function and mental arithmetic/working memory predicted 6-month FCI
      performance (R = 0.79), and a third model found that these 2 measures at baseline
      predicted 6-month FCI performance (R = 0.71). CONCLUSIONS: Multiple cognitive
      functions are associated with initial impairment and partial recovery of FC in
      moderate-to-severe TBI patients. In particular, arithmetic, working memory, and
      executive function skills appear critical to recovery of FC in TBI. The study
      results represent an initial step toward developing a neurocognitive model of FC
      in patients with TBI.

PMID- 23131975
TI  - Results of radical cystectomy with Mainz pouch II diversion (single institution
      experience).
AB  - Evaluation of the peri- and postoperative morbidity in patients who underwent
      radical cystectomy and sigma-rectum pouch (Mainz pouch II) diversion with
      curative intent for invasive bladder cancer.  We've reviewed 320 patients with
      invasive bladder cancer who underwnt radical cystectomy with lymphadenectomy and
      urinary diversion in our clinic from 1988 to 2011. In 134 (41.9%) patients Mainz
      pouch II diversion was performed. The results and complication rates have been
      analyzed in these patients.   Intraoperaive injury of the rectum occurred in 2
      (1.5%) patient, early complications were found in 40 (29.9%) and late
      complications in - 5 (3.7%) patients. Oral alkalization was necessary in 30
      (22.4%) cases. 9 (6.7%) patients were hospitalized because of severe acidosis.
      Acute pyelonephritis developed in 8 (5.9%) patients. Hydronephrosis developed in
      15 (11.2%) cases. In 7 (5.2%) patients dilatation of upper urinary tract was
      bilateral and in 8 (5.9%) - unilateral. In 4 (2.9%) patients stricture of the
      ureteral anastomosis was diagnosed. All patients were dry at day time. Only three
      (2.2%) patients (2 male and 1 female) needed pads at night time. All of these
      three patients were above 70 years old. Two patients underwent surgical
      intervention for interintestinal abscess. One patient was operated because of
      mechanical bowel obstruction 2 month after surgery. Perioperative mortality was
      3.7%.  Mainz Pouch II has a low morbidity and mortality rates. This form of
      diversion is method of choice for patients in whom the urethra cannot be used. In
      selected cases Mainz Pouch II is alternative to other types of continent
      diversion.

PMID- 23131976
TI  - [Body mass of pregnant females, as a risk factor for the development of obstetric
      complications].
AB  - To elucidate the specific courses of the course of pregnancy and labor in
      patients with obesity and inadequate body mass.  280 women (pregnant females aged
      17-38) clinically followed up for pregnancy and labor. The nutritional status was
      estimated by the Quetle index (QI).  Complications of pregnancy were more common
      in females with insufficient and excessive body mass. There are gestational
      diabetes, gestoses,uterine inertia,fetal macrosomy and perinatal mortality was
      observed in 67 % of the obese women , total number of spontaneous abortions was 9
      % cases, in females with inadequete body mass. The neonatal outcomes of pregnancy
      and complications of labor were better in the pregnant females, who had normal
      QI. Thus, insufficient and/or excersive body mass is premorbid negative
      background and risk factor for the development of obstetric complications.
      Further studies will allow us to get answers to some of the issues raised and to
      the management of pregnant women with obesity and low levels of IQ.

PMID- 23131977
TI  - [The importance of local and general factors in development of inflammatory
      periodontal diseases in children and adolescents].
AB  - The aim of the study was to investigate the influence of local and general
      adverse risk factors and their role in the development of inflammatory
      periodontal diseases in children and adolescents.  The study of the dental status
      among 618 school children, 9 to 15 years of age has been performed.  The obtained
      results revealed an ambiguous influence of general and local risk factors on the
      development of inflammatory periodontal diseases. Namely, among the general risk
      factors the main role is given to hormonal functioning state of juvenile age
      (26.5%) - (arhythmia formation of hormonal activity).  Among the local risk
      factors inducing inflammatory periodontal diseases at young age, the most
      significant are tooth-jaw anomalies (32.2%), especially - dental occlusion
      pathology, lips' bridle attachment anomalies, absence of interdental contacts,
      small vestibule of the mouth and so on. Poor oral hygiene, however, is also a
      significant factor in all age groups.  Definition of the role and importance of
      general and local risk factors, taking into consideration patient's age, is of
      great importance in organization of early prevention, giving the possibility to
      predict disease possible development, choose most appropriate way to treat the
      specific situation, reduce the need of complex treatment and improve treatment
      outcomes.

PMID- 23131978
TI  - [Problem of motivation of the population to prevention and treatment dental
      diseases].
AB  - Dental health is an integral part of a normal state of a human body and, first of
      all, depends on knowledge of the population of bases of individual hygiene of an
      oral cavity and ability to use them in practical life. Numerous researches
      indicate low level of knowledge of the population in questions of prevention of
      dental diseases and individual hygiene of an oral cavity that testifies to
      existence of problems in the organization of sanitary education.  Existing
      practice of hygienic training and education, in a certain measure, lags behind
      modern requirements, and some questions demand specification and optimization.
      For efficiency of sanitary and preventive actions it is necessary to study
      character and motivation structure to prevention and treatment of dental diseases
      and to develop an effective method of its increase. Therefore actual search of
      new forms of psycho hygiene and psycho prevention with use of modern information
      technologies which should provide high level of dental health of the military
      personnel is represented.  The purpose of the real research was establishment of
      the factors forming motivation to prevention and treatment of the main dental
      diseases, and development of a psycho physiological method of its increase.  The
      carried-out research allows to expand and systematize ideas necessary for the
      practical doctor of the major factors forming motivation to prevention and
      treatment of the main dental diseases. Development of an objective technique of a
      complex assessment of level of motivation of patients to prevention and treatment
      of dental pathology will allow to prove the new perspective direction of the
      sanitary educational work, allowing to reduce fobiya level, effectively to
      increase motivation of the patient to receiving the timely dental help.  It
      especially is important if to consider that numerous programs of hygienic
      training and the education, applied in our country, didn't lead to change of
      hygienic skills of the population in expected scales. At the same time, priority
      questions in prevention of caries and diseases of a periodontium there is a
      hygienic education and training to methods and means of clarification of a mouth.

PMID- 23131979
TI  - Multimodal approach to anesthetic management of long-term operative
      interventions.
AB  - The aim of our investigation is the evaluation of multi-modal approach to
      anesthetic management during general anesthesia in comparison to traditional
      general anesthesia.  40 patients being inpatient to RRCEM from 2008 to 2009 have
      been investigated. Patients were divided into two groups according to the method
      of anesthesia performed: patients (n=20) who underwent multi-modal anesthesia;
      patients (n=20) of control group who underwent traditional general anesthesia.
      Multi-modal anesthetic management with the force to all parts of pain
      pathogenesis promotes the stability of hemodynamic indications in post-operative
      period, to minimum tension of homeostasis, less expressed reaction of
      sympathoadrenal system due to good neurovegetative protection.

PMID- 23131960
TI  - Monitoring of nonsteroidal immunosuppressive drugs in patients with lung disease
      and lung transplant recipients: American College of Chest Physicians evidence
      based clinical practice guidelines.
AB  - OBJECTIVES: Immunosuppressive pharmacologic agents prescribed to patients with
      diffuse interstitial and inflammatory lung disease and lung transplant recipients
      are associated with potential risks for adverse reactions. Strategies for
      minimizing such risks include administering these drugs according to established,
      safe protocols; monitoring to detect manifestations of toxicity; and patient
      education. Hence, an evidence-based guideline for physicians can improve safety
      and optimize the likelihood of a successful outcome. To maximize the likelihood
      that these agents will be used safely, the American College of Chest Physicians
      established a committee to examine the clinical evidence for the administration
      and monitoring of immunosuppressive drugs (with the exception of corticosteroids)
      to identify associated toxicities associated with each drug and appropriate
      protocols for monitoring these agents. METHODS: Committee members developed and
      refined a series of questions about toxicities of immunosuppressives and current
      approaches to administration and monitoring. A systematic review was carried out
      by the American College of Chest Physicians. Committee members were supplied with
      this information and created this evidence-based guideline. CONCLUSIONS: It is
      hoped that these guidelines will improve patient safety when immunosuppressive
      drugs are given to lung transplant recipients and to patients with diffuse
      interstitial lung disease.

PMID- 23131980
TI  - [Impaired fasting glycaemia as a risk factor of coronary heart disease].
AB  - The aim of the research was to study the prevalence of early carbohydrate
      metabolism disorders and their relationship to coronary heart disease (CHD) risk
      factors (RF) in the female population. Epidemiological studies were carried out
      on 952 women aged 20-59 years. The frequency of impaired fasting glycaemia (IFG)
      was 4,6 %, and the impaired glucose tolerance (IGT) found only 0,2%. It was found
      that the prevalence of CHD in female population is found in 2 times more often in
      the presence of IFG than in its absence (40,0% and 23,2 %, respectively),
      observed in almost all age groups except 20-29 years, where CHD totally absent in
      individuals with IFG. The detection rate of the RF of cardiovascular disease with
      and without IFG also somewhat different: for example, hypertension,
      hypertriglyceridemia, hypercholesterolemia, obesity, is the criterion of the
      presence of metabolic syndrome, met with greater frequency in the presence of
      IFG.

PMID- 23131981
TI  - [The prevalence of main risk factors of CHD in women according to epidemiological
      and clinical examination].
AB  - The aim of the research was to study the prevalence of main risk factors of
      coronary heart disease (CHD) in 200 women aged 30-59 years, according to
      epidemiological and clinical examination. It was found that the most common risk
      factors in women with CHD are abdominal obesity (AO), body mass index (BMI),
      triglycerides (TG), and hypercholesterolemia, with a somewhat lower rate - low
      physical activity (LPA), LDL cholesterol , atherogenical index, AH and HDL
      cholesterol. All risk factors, except for the LPA occur with greater frequency in
      the group of clinical examination compared to epidemiological. In women of
      fertility age and menopause all risk factors, except AH recorded almost the same
      frequency and only AH was more frequently diagnosed in women in menopause, as in
      epidemiological and clinical examination.

PMID- 23131982
TI  - [Insulin resistance disturbances in patients with HCV infection].
AB  - The aim of investigation was to study the impact of insulin resistance in
      patients with HCV infection. 130 patients were investigated: 20 with acute
      hepatitis C; 38 with chronic hepatitis C; 72 with cirrhosis. The study
      demonstrated, that the serum level of C-peptide and Insulin in patients with
      liver cirrhosis is higher, than in patients with acute and chronic HCV infection.
      This is necessary the monitoring of patients with insulin resistance, which will
      contribute to the prevention of complications and can improve patients' quality
      of life.

PMID- 23131984
TI  - Our experience of neurovascular bundles surgical treatment interposition at
      transcondylar and supracondylar fractures of humeral bone at children.
AB  - The main aim of the study was to discuss the modern approach to the diagnoses and
      surgical treatment of fractures of humerus in children, associated with
      compromised neurovascular status and signs of acute ischemia.  The 10 year
      experience was analyzed, with frequency of complications, varied from 0, 68% to
      9% between the group. The age, sex, mechanism of injury and neurovascular status
      were recorded in all 31 patients.  Our data suggested, that aggressive surgical
      approach, when indicated, is corresponding with well-reduced fracture in proper
      alignment with a viable and warm functional extremity in 93,5% of cases.

PMID- 23131983
TI  - [Genetic structure of hepatitis B and C virus population circulating among
      healthy and high risk of parenteral contamination individuals in Azerbaijan].
AB  - Considering that information on genetical features of hepatitis B (HBV) and
      hepatitis C (HCV) viruses populations, circulating in Azerbaijan remains limited,
      authors by means of adequate serological and molecular-genetical methods defined
      major genetical parameters of HBV and HCV, identified among blood donors living
      in Azerbaijan and persons from groups with high risk of contamination with HBV
      and HCV.  It was established that population of HBV is presented by dominating
      "wild" variant of HBV and mutant variants of HBV, defective on ability of
      producing HBeAg, HBcAg and even HBsAg. Thus more than 90% of HBV isolates
      belonged to D genotype, and less, than 10% - to A genotype.  It is shown that
      population of HCV is presented by three genotypes: "1", "2" and "3", and the
      ratio of identification frequencies of these genotypes made approximately
      71%:9%:20%, accordingly.

PMID- 23131985
TI  - Child and adolescent body mass index data according to who new child growth
      standards in Georgia (Kakheti region).
AB  - The Studies were carried in Georgia among 6-18 years old 854 children and
      adolescent; (417girls, 437 boys). Measurements of weight, height and chest
      circumference were taken from following standard techniques. The Body Mass Index
      of each child was computed as weight/height2. The calculated BMI was compared to
      the World Health Organization BMI - for-age centiles tables (5-19 years old girls
      and boys). According the given results the nutritional status was defined:
      thinness-2.6%, overweight- 13%, obesity-7.2%. The most 6-18 years old children
      BMI is adequate to 25th, 50th and 75th centiles of the World Health Organization
      standard BMI -for-age percentile tables. The thinness was revealed only among the
      children of 6-12 age group. With the prevalence among the girls. The high number
      of thin children is fixed with both 6 years. old girls and boys(6.4%).12 years
      old girls (11.1%),but the number of underweight children is less than the number
      of the same age schoolchildren in Tbilisi. The number of fat and overweighted
      children increases within the age and dominates among the boys. The highest
      percent of obesity was revealed among the children of both sex at the age of 11
      (21.5%) also among the 18 years old boys(17.6%). The data analysis of the carried
      studies, allow comparisons with the other studies, carried out in different
      countries of the world. The data analysis showed that underweight, overweight and
      obesity distribution among the schoolchildren in Georgia is close to the
      statistics data of the Eastern and Central Europian countries.

PMID- 23131986
TI  - [Per os given bacteriophages changes the clinical course of diseases caused by
      bacterial agents in children].
AB  - The aim of the study was to reveal the possible effect of perorally given
      bacteriophages on the clinical course of diseases caused by infectious agents in
      children.   The complex therapy with inclusion of bacteriophages was performed in
      85 children aged from 1 week to 15 years, 36 girls, 47 boys with following
      diagnoses: sepsis, bacterial diarrhea, urinary tract infections, bacterial
      infections of upper respiratory ways, bacterial pneumonia. For every case an
      appropriate analoguous control was matched. Thus this open clinical trial was
      carried out according to the Case Control Study design. Clinical and paraclinical
      markers specific for different diseases and integrated index of the gravitidy of
      condition. defined by the method of multicriterial analyzis with usage of Fuzzy
      logic approaches were revealed in dynamics.   It was established that by peroral
      treatment with commercial bacteriophages the positive trends of investigated
      parameters had place. The improvement of the integrated index of gravitidy was
      most pronounced. We suppose that obtaining of more convincing evidences of the
      clinical value of bacteriophagetherapy the further studies in the more number of
      patients with the usage of the generally accepted double blind method should be
      conducted.

PMID- 23131987
TI  - [Role of lung affection in development of catecholamine-induced myocardial injury
      and its correction  (experimental study)].
AB  - The present research was focused on studies of adrenaline-induced morphological
      and biochemical alterations in rat lungs and myocardium and prevention of these
      changes by improvement of alveolar gas exchange.   The results obtained allow
      concluding that adrenaline-induced myocardial injury is a result of primary
      affection of lungs and suppression of alveolar gas exchange leading to
      generalized hypoxia and affection of cardiomyocytes. This is evidenced by
      prevention of myocardial injury in rats when preliminarily exposed to the
      mechanical lung ventilation prior to adrenaline injection.

PMID- 23131988
TI  - [Impact of thymosin-alpha1 on reproduction of herpes simplex virus in cell system
      and on course of acute experimental infection in mice].
AB  - The article contains results of laboratory and experimental investigation carried
      out for comparative estimation of antiviral activity of thymosin-alpha1 (Ta1)
      against herpes simplex virus (HSV).   It was demonstrated that administration of
      tymosin-alpha1 in cultivated in vitro cellular system had been inoculated with
      HSV provided inhibition of HSV reproduction and defense of cells of HSV
      cytopathogenic action. Moreover Ta1 ability to inhibit HSV reproduction in cell
      was comparable with the same ability of human alpha-interferon.  Besides it was
      demonstrated that Ta1 parenteral administration to mice infected with HSV leaded
      to reduce of mice morbidity percent and prolonged of their survival rate. Ta1
      ability to depress experimental viral infection development was higher than same
      ability of acyclovir.

PMID- 23131989
TI  - Bioarchaeological research development in Georgia: steps, peculiarities,
      directions.
AB  - In Georgia, Bioarcheology in its broad sense started developing with the research
      in Paleoanthropology and Paleopathology. Paleoanthropology initially developed in
      line with Archaeology. The study of biomaterial through the angle of
      paleopathology started in 1956. Later works were devoted to Ethnogenesis,
      comparative Anthropology, spreading physiological stresses and other issues. In
      recent years newly discovered rich archeological materials and introduction of
      the modern methods of research has outlined new prospects, and our decision is to
      put them in to action. From our point of view the research methods and aims of
      Bioarchaeology include: 1. morphological study of biomaterial on the macroscopic
      level. 2. The research through chemical methods which gives us an opportunity to
      outline many parameters of life such as eating habits, the aspects of
      interrelation with the environment and metabolic processes through the spectrum
      analysis of main ingredients of material. The important part of this direction is
      the researching of stable isotopes which gives us additional and strong
      arguments. 3. Genetic research answers the following important questions:
      biomaterial's variety; racial and ethnic origin; time and place of migration
      processes traced on ethnogenesis; hereditary disease history (dating, the origin
      of the diseases, epidemics and other); human and animal genome evolution and
      mutational changes; the role of environment (food, ecosystems) in genome changes.
      The results of the above mentioned research allow answering a lot of important
      historical and biomedical issues. From these, we have started the comparative
      analyses of the Genographic data of Georgia, taking notes of the genetic changes
      which, in our opinion, are caused by the radical and stable changes of eating
      habits produced about 450-500 years ago, which probably resulted proportional
      imbalance of the diseases that appeared in the same period.

PMID- 23131990
TI  - [Herbal infusions for treatment of epilepsy (review)].
AB  - On the basis of literature data the possibility of using herbal infusions to
      treat epilepsy was studied and medical properties and the chemical composition of
      herbal infusions described in the literature were examined. The most often used
      plants were selected. On the base on these data the optimal variant of herbal
      infusion was composed. The effect of herbal infusion was studied on 60 rats. It
      is shown that in animals treated with herbal infusions, compared with the control
      group, decreased tonic traction, duration of seizures decreased by 71%, while
      their occurrence by 60% and animal survival increased by 67%. All these data
      indicate the potential effectiveness of herbal infusions.

PMID- 23131993
TI  - Genetic ablation of the tetraspanin CD151 reduces spontaneous metastatic spread
      of prostate cancer in the TRAMP model.
AB  - Tetraspanins are integral membrane proteins that associate with motility-related
      molecules such as integrins. Experimental studies have indicated that they may be
      important regulators of tumor invasion and metastasis, and high expression of the
      tetraspanin CD151 has been linked to poor prognosis in a number of cancers. Here,
      we show for the first time that genetic ablation of CD151 inhibits spontaneous
      metastasis in a transgenic mouse model of de novo tumorigenesis. To evaluate the
      effects of CD151 on de novo prostate cancer initiation and metastasis, a Cd151(-/
      ) (KO) murine model was crossed with the Transgenic Adenocarcinoma of Mouse
      Prostate (TRAMP) model. Mice were analyzed for initiation of prostate tumor by
      palpation and primary tumors were analyzed by immunohistochemistry. Liver and
      lungs were examined for incidence and size of spontaneous metastatic lesions by
      histopathology. Knocking-out Cd151 had no significant effect on prostate cancer
      initiation or on expression of markers of proliferation, apoptosis, or
      angiogenesis in primary tumors. However, it did significantly decrease metastasis
      in a site-specific fashion, notably to the lungs but not the liver. Thus, CD151
      acts principally as promoter of metastasis in this model. Prostate cancer is the
      second highest cause of cancer-related deaths in men in most Western countries,
      with the majority of deaths attributed to late-stage metastatic disease. CD151
      may prove to be a valuable prognostic marker for treatment stratification and is
      a possible antimetastatic target.

PMID- 23131992
TI  - Persistent organic pollutants and type 2 diabetes: a prospective analysis in the
      nurses' health study and meta-analysis.
AB  - BACKGROUND: Prospective data regarding persistent organic pollutants (POPs) and
      risk of type 2 diabetes (T2D) are limited, and the results for individual POPs
      are not entirely consistent across studies. OBJECTIVES: We prospectively examined
      plasma POP concentrations in relation to incident T2D and summarized existing
      evidence in a meta-analysis. METHODS: Plasma polychlorinated biphenyls (PCBs),
      dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethylene (DDE),
      and hexachlorobenzene (HCB) concentrations were measured in 1,095 women who were
      free of diabetes at blood draw in 1989-1990 and participated in two case-control
      studies in the Nurses' Health Study. We identified 48 incident T2D cases through
      30 June 2008. We conducted a literature search in PubMed and EMBASE through
      December 2011 to identify prospective studies on POPs in relation to diabetes. We
      used a fixed-effects model to summarize results. RESULTS: After multivariable
      adjustment, plasma HCB concentration was positively associated with incident T2D
      [pooled odds ratio (OR) 3.59 (95% CI: 1.49, 8.64, ptrend = 0.003) comparing
      extreme tertiles]. Other POPs were not significantly associated with diabetes.
      After pooling our results with those of six published prospective studies that
      included 842 diabetes cases in total, we found that HCB and total PCBs both were
      associated with diabetes: the pooled ORs were 2.00 (95% CI: 1.13, 3.53; I2 =
      21.4%, pheterogeneity = 0.28) and 1.70 (95% CI: 1.28, 2.27; I2 = 16.3%,
      pheterogeneity = 0.30) for HCB and total PCBs, respectively. CONCLUSIONS: These
      findings support an association between POP exposure and the risk of T2D.

PMID- 23131994
TI  - Multiple functions of sushi domain containing 2 (SUSD2) in breast tumorigenesis.
AB  - Routinely used therapies are not adequate to treat the heterogeneity of breast
      cancer, and consequently, more therapeutic targets are desperately needed. To
      identify novel targets, we generated a breast cancer cDNA library enriched for
      genes that encode membrane and secreted proteins. From this library we identified
      SUSD2 (Sushi Domain Containing 2), which encodes an 822-amino acid protein
      containing a transmembrane domain and functional domains inherent to adhesion
      molecules. Previous studies describe the mouse homolog, Susd2, but there are no
      studies on the human gene associated with breast cancer. Immunohistochemical
      analysis of human breast tissues showed weak or no expression of SUSD2 in normal
      epithelial cells, with the endothelial lining of vessels staining positive for
      SUSD2. However, staining was observed in pathologic breast lesions and in lobular
      and ductal carcinomas. SUSD2 interacts with galectin-1 (Gal-1), a 14-kDa secreted
      protein that is synthesized by carcinoma cells and promotes tumor immune evasion,
      angiogenesis, and metastasis. Interestingly, we found that localization of Gal-1
      on the surface of cells is dependent on the presence of SUSD2. Various phenotype
      assays indicate that SUSD2 increases the invasion of breast cancer cells and
      contributes to a potential immune evasion mechanism through induction of
      apoptosis of Jurkat T cells. Using a syngeneic mouse model, we observed
      accelerated tumor formation and decreased survival in mice with tumors expressing
      Susd2. We found significantly fewer CD4 tumor infiltrating lymphocytes in mice
      with tumors expressing Susd2. Together, our findings provide evidence that SUSD2
      may represent a promising therapeutic target for breast cancer.

PMID- 23131995
TI  - Time to adjuvant chemotherapy and survival in non-small cell lung cancer: a
      population-based study.
AB  - BACKGROUND: The time interval between surgery and initiation of adjuvant
      chemotherapy (ACT) may impact survival in colorectal and breast cancers. This is
      the first report describing the association between time to adjuvant chemotherapy
      (TTAC) and survival in non-small cell lung cancer (NSCLC). METHODS: All cases of
      NSCLC diagnosed in Ontario, Canada, from 2004 to 2006 who underwent surgical
      resection (n = 3354) were identified using the Ontario Cancer Registry. TTAC was
      defined as the interval between dates of surgery and initiation of ACT. Factors
      associated with TTAC greater than 10 weeks were evaluated by logistic regression.
      The Cox proportional hazards model was used to describe the effect of delayed
      TTAC (analyzed as a continuous variable) on overall survival. RESULTS: Among the
      1032 cases treated with ACT, the median TTAC was 8 weeks (range, 1-16 weeks); 35%
      of cases initiated ACT more than 10 weeks after surgery. Rates of TTAC greater
      than 10 weeks varied widely across regions (11%-50%, P = .001). There was no
      significant association between increased comorbidity and delayed TTAC; there was
      a trend toward greater delay in TTAC with longer postoperative hospital stay (P =
      .054) and postoperative readmission to hospital (P = .056). Male sex, higher
      stage of disease, greater comorbidity, and more extensive surgery were
      independently associated with inferior survival. TTAC was not associated with
      overall survival (odds ratio = 1.00, 95% confidence interval = 0.99-1.00).
      CONCLUSIONS: One-third of NSCLC patients treated with ACT in the general
      population start ACT beyond 10 weeks after surgery. Delayed TTAC does not appear
      to be associated with inferior survival in NSCLC.

PMID- 23131996
TI  - Service reconfiguration: impact and implications.

PMID- 23131997
TI  - Reusable invasive medical devices: clean and prepare.

PMID- 23131998
TI  - Annual review for housebound patients with coronary heart disease.
AB  - The care of people with long-term conditions is a priority for the NHS. While
      there are many strategies in place in primary care to support the management of
      patients with long-term conditions, there is a paucity of services for people who
      are housebound. Coronary heart disease (CHD) is the most common cause of death in
      the UK and costs more than L9 billion every year (British Heart Foundation,
      2012). This article describes a pilot project set up by a nurse, working under an
      honourary contract within a general practice. The project's aim was to deliver a
      service, to housebound patients with CHD, which would provide an annual review of
      their condition in the home. This pilot provided some justification for the
      expansion of the service to all housebound patients who have a long-term
      condition, ensuring that they receive the same equitable assessment, treatment
      and health promotion advice afforded to those able to come into the practice.
      Some of the findings from the patient visits are discussed and a case is made for
      the expansion of the project beyond the pilot.

PMID- 23131999
TI  - How national policy affects the care of patients who suffer a heart attack.
AB  - In October 2008 the Department of Health published the National Infarct
      Angioplasty Project (NIAP), reviewing its guidance on the treatment of a heart
      attack. This was framed to update previous 2000 guidance from the National
      Service Framework for coronary heart disease, and highlighted the need for
      specialised services and 24-hour care. Recommendations included the need for
      appropriate assessment/investigation and immediate transfer to a cardiac
      catheterisation laboratory for primary angioplasty within 120 minutes of calling
      for professional help. Cardiac services are currently undergoing review, and a
      significant number of new cardiac catheterisation laboratories are being
      established throughout the country to accommodate the needs of this client group.
      This article discusses whether 24-hour care is feasible, cost-effective and
      realistic for the NHS to manage, as well as analysing policy guidelines in
      relation to the treatment of heart attack.

PMID- 23132000
TI  - Parents' experiences of their child's first anaesthetic in day surgery.
AB  - BACKGROUND: Parents play an important part in their child's anaesthesia. When a
      child has to receive anaesthesia, it is of great importance that parents are
      there by his/her side as children depend on them for support. Many parents worry
      and experience fear before their child's anaesthesia and studies show that there
      is a correlation between a worried parent and a worried child. AIM: The purpose
      of this study was to illustrate the meaning of being a parent at one's child's
      first anaesthesia in day surgery. METHOD: Six parents were interviewed and data
      were analysed using a descriptive qualitative approach inspired by phenomenology.
      RESULT: The phenomenon, 'a child's first anaesthesia in day surgery as
      experienced by parents' is based on the following components: ambivalence between
      worry and relief, a feeling of losing control, needing to be prepared, being able
      to be present and a need of emotional support. CONCLUSION: Specific individually
      adapted information with a compulsory preoperative visit, presence and
      participation from, if possible, both parents at their child's anaesthesia but
      also designated staff from the anaesthetic team to focus solely on supporting the
      parents at their child's anaesthesia induction can improve the conditions for
      security.

PMID- 23132001
TI  - Transformational leadership  in nursing practice.
AB  - Traditionally, nurses have been over-managed and led inadequately, yet today they
      face unprecedented challenges and opportunities. Organisations constantly face
      changes that require an increasingly adaptive and flexible leadership. This type
      of adaptive leadership is referred to as 'transformational'; under it,
      environments of shared responsibilities that influence new ways of knowing are
      created. Transformational leadership motivates followers by appealing to higher
      ideas and moral values, where the leader has a deep set of internal values and
      ideas. This leads to followers acting to sustain the greater good, rather than
      their own interests, and supportive environments where responsibility is shared.
      This article focuses on transformational leadership and its application to
      nursing through the four components of transformational leadership. These are:
      idealised influence; inspirational motivation; intellectual stimulation; and
      individual consideration.

PMID- 23132002
TI  - Debating mental health nurses'  role in medicines management.
AB  - This article delineates concordance and adherence; two fundamental positions
      pertaining to the role of the nurse in medicine management. Taking the form of a
      debate, it uses mental health nursing to describe the role and function of
      concordance and adherence in practice. Each author presents their case and
      responds briefly to the other in order to show why they see the adoption of one
      term or another as central to medicines interventions with the patient. The
      purpose of the paper is to encourage readers to consider their own position in
      relation to this important debate.

PMID- 23132003
TI  - Telephone triage assessment for musculoskeletal disorders: part 1.
AB  - Changes in the delivery of occupational health and wellbeing services can affect
      the employer, employees and service users. Despite the impact of such changes,
      many organisations implement them without understanding their true effects.
      Support of staff and service users is needed if change is to be implemented and
      services reconfigured to improve overall efficiency. A diagnostic analysis has
      been recommended as a precursor to assess what impact a change would have. This
      paper explores the process of a diagnostic analysis before nursing telephone
      triage assessment for musculoskeletal disorders was implemented in an
      occupational health and wellbeing service. Mixed methods were used to gather the
      relevant information.

PMID- 23132004
TI  - New standards for hospital food.

PMID- 23132005
TI  - Swings and roundabouts in the quality of care in acute hospitals.
AB  - John Tingle discusses a recent report on the quality of care in acute hospitals
      by the Royal College of Physicians, which warns that acute hospital care could be
      on the brink of collapse.

PMID- 23132006
TI  - Teaching and learning: from staff nurse to nurse consultant. Part 10: teaching a
      caring attitude.

PMID- 23132007
TI  - Withdrawing and withholding  life-sustaining treatment.
AB  - There has been considerable criticism recently over the use of end-of-life
      pathways and do-not-resuscitate orders with vulnerable, incapable patients, often
      without discussion. This criticism has led to press and judicial scrutiny of the
      lawfulness of decisions to withdraw or withhold life-sustaining treatment. In
      this article, the author reviews the law and argues that flawed decision-making
      by doctors and nurses, rather than the actual end-of-life pathway or do-not
      resuscitate order, is where the lawfulness of withdrawing and withholding
      treatment must be challenged.

PMID- 23132008
TI  - Following the inspiration of those along the way.
AB  - Deborah Easby is a third year student nurse at Sheffield Hallam University, now
      nearing the end of her studies. With 18 years of experience in health care behind
      her and two children in tow, Deborah decided to become a nurse. In this issue's
      column, she reflects on her experience of studying nursing and attending varied
      clinical placements as a mature student nurse.

PMID- 23132009
TI  - Nursing care-then and now.

PMID- 23132010
TI  - Gold nanorods as dual photo-sensitizing and imaging agents for two-photon
      photodynamic therapy.
AB  - Gold nanorods with three different aspect ratios were prepared and their dual
      capabilities for two-photon imaging and two-photon photodynamic therapy have been
      demonstrated. These gold nanorods exhibit large two-photon absorption action
      cross-sections, about two orders of magnitude larger than small organic
      molecules, which makes them suitable for two-photon imaging. They can also
      effectively generate singlet oxygen under two-photon excitation, significantly
      higher than traditional photosensitizers such as Rose Bengal and Indocyanine
      Green. Such high singlet oxygen generation capability under two-photon excitation
      was ascribed to their large two-photon absorption cross-sections.
      Polyvinylpyrrolidone (PVP) coated gold nanorods displayed excellent
      biocompatibility and high cellular uptake efficiency. The two-photon photodynamic
      therapy effect and two-photon fluorescence imaging properties of PVP coated gold
      nanorods have been successfully demonstrated on HeLa cells in vitro using
      fluorescence microscopy and indirect XTT assay method. These gold nanorods thus
      hold great promise for imaging guided two-photon photodynamic therapy for the
      treatment of various malignant tumors.

PMID- 23132011
TI  - Juice, pulp and seeds fractionated from dry climate primocane raspberry cultivars
      (Rubus idaeus) have significantly different antioxidant capacity, anthocyanin
      content and color.
AB  - Raspberries contain flavonoid antioxidants whose relative concentrations may vary
      between the juice, pulp, and seed fractions. Oxygen radical absorbance capacity
      (ORAC), total anthocyanin content, and berry color were determined for six
      cultivars of primocane raspberries grown in a dry climate (Utah, USA).
      Significant ORAC differences were found between juice (18.4 +/- 0.39 MUmol TE/g),
      pulp (24.45 +/- 0.43), and seeds (273.27 +/- 11.15) with all Utah cultivars
      combined. A significantly higher concentration of anthocyanins was present in
      Utah raspberry juice (20.86 +/- 0.35 mg cyanidin-3-glucoside eq./100 g), compared
      to pulp (13.96 +/- 0.35). Anthocyanin content of juice and pulp were
      significantly positively correlated with dark color (L*). This is the first
      report of fractional differences in dry climate raspberries, and has implications
      for the juice and supplement industries.

PMID- 23132013
TI  - Buffer the pain away: stimulating the right ventrolateral prefrontal cortex
      reduces pain following social exclusion.

PMID- 23132014
TI  - High strain rate deformation of layered nanocomposites.
AB  - Insight into the mechanical behaviour of nanomaterials under the extreme
      condition of very high deformation rates and to very large strains is needed to
      provide improved understanding for the development of new protective materials.
      Applications include protection against bullets for body armour, micrometeorites
      for satellites, and high-speed particle impact for jet engine turbine blades.
      Here we use a microscopic ballistic test to report the responses of periodic
      glassy-rubbery layered block-copolymer nanostructures to impact from
      hypervelocity micron-sized silica spheres. Entire deformation fields are
      experimentally visualized at an exceptionally high resolution (below 10 nm) and
      we discover how the microstructure dissipates the impact energy via layer
      kinking, layer compression, extreme chain conformational flattening, domain
      fragmentation and segmental mixing to form a liquid phase. Orientation-dependent
      experiments show that the dissipation can be enhanced by 30% by proper
      orientation of the layers.

PMID- 23132012
TI  - Role of contrast media on oxidative stress, Ca(2+) signaling and apoptosis in
      kidney.
AB  - Contrast media (CM)-induced nephropathy is a common cause of iatrogenic acute
      renal failure. The aim of the present review was to discuss the mechanisms and
      risk factors of CM, to summarize the controlled studies evaluating measures for
      prevention and to conclude with evidence-based strategies for prevention. A
      review of the relevant literature and results from recent clinical studies as
      well as critical analyses of published systematic reviews used MEDLINE and the
      Science Citation Index. The cytotoxicity induced by CM leads to apoptosis and
      death of endothelial and tubular cells and may be initiated by cell membrane
      damage together with reactive oxygen species (ROS) and inflammation. Cell damage
      may be aggravated by factors such as tissue hypoxia, properties of individual CM
      such as ionic strength, high osmolarity and/or viscosity. Clinical studies indeed
      support this possibility, suggesting a protective effect of ROS scavenging with
      the administration of N-acetylcysteine, ascorbic acid erdosteine, glutathione and
      bicarbonate infusion. The interaction between extracellular Ca(2+), which plays a
      central role in intercellular contacts and production of ROS, and the in vitro
      toxicity of CM was also reviewed. The current review addresses the role of
      oxidative stress in the pathogenesis of CM in the kidney as well as current and
      potential novel treatment modalities for the prevention of neutrophil activation
      and CM-induced kidney degeneration in patients. ROS production through CM-induced
      renal hypoxia may exert direct tubular and vascular endothelial injury.
      Preventive strategies via antioxidant supplementation include inhibition of ROS
      generation or scavenging.

PMID- 23132015
TI  - High-efficiency Cooper pair splitting demonstrated by two-particle conductance
      resonance and positive noise cross-correlation.
AB  - Entanglement is at the heart of the Einstein-Podolsky-Rosen paradox, where the
      non-locality is a necessary ingredient. Cooper pairs in superconductors can be
      split adiabatically, thus forming entangled electrons. Here, we fabricate such an
      electron splitter by contacting an aluminium superconductor strip at the centre
      of a suspended InAs nanowire. The nanowire is terminated at both ends with two
      normal metallic drains. Dividing each half of the nanowire by a gate-induced
      Coulomb blockaded quantum dot strongly impeds the flow of Cooper pairs due to the
      large charging energy, while still permitting passage of single electrons. We
      provide conclusive evidence of extremely high efficiency Cooper pair splitting
      via observing positive two-particle correlations of the conductance and the shot
      noise of the split electrons in the two opposite drains of the nanowire.
      Moreover, the actual charge of the injected quasiparticles is verified by shot
      noise measurements.

PMID- 23132016
TI  - Lithium-sulphur batteries with a microporous carbon paper as a bifunctional
      interlayer.
AB  - The limitations in the cathode capacity compared with that of the anode have been
      an impediment to advance the lithium-ion battery technology. The lithium-sulphur
      system is appealing in this regard, as sulphur exhibits an order of magnitude
      higher capacity than the currently used cathodes. However, low active material
      utilization and poor cycle life hinder the practicality of lithium-sulphur
      batteries. Here we report a simple adjustment to the traditional lithium-sulphur
      battery configuration to achieve high capacity with a long cycle life and rapid
      charge rate. With a bifunctional microporous carbon paper between the cathode and
      separator, we observe a significant improvement not only in the active material
      utilization but also in capacity retention, without involving complex synthesis
      or surface modification. The insertion of a microporous carbon interlayer
      decreases the internal charge transfer resistance and localizes the soluble
      polysulphide species, facilitating a commercially feasible means of fabricating
      the lithium-sulphur batteries.

PMID- 23132017
TI  - Unique fingering instabilities and soliton-like wave propagation in thin
      acoustowetting films.
AB  - Acoustic-fluid interactions not only has had a long history but has recently
      experienced renewed scrutiny because of their vast potential for microscale fluid
      and particle manipulation. Here we unravel a fascinating and anomalous ensemble
      of dynamic 'acoustowetting' phenomena in which a thin film drawn from a sessile
      drop first spreads in opposition to the acoustic wave propagation direction. The
      advancing film front then exhibits fingering instabilities akin to classical
      viscous fingering, but arising through a different and novel mechanism:
      transverse Fresnel diffraction of the underlying acoustic wave. Peculiar 'soliton
      like' wave pulses are observed to grow above these fingers, which, on reaching a
      critical size, translate away along the wave propagation direction. By
      elucidating the complex hydrodynamics underpinning the spreading, and associated
      flow reversal and instability phenomena, we offer insight into the possibility of
      acoustically controlling fast and uniform film spreading, constituting a flexible
      and powerful alternative for microfluidic transport.

PMID- 23132019
TI  - Non-equilibrium dynamics of an unstable quantum pendulum explored in a spin-1
      Bose-Einstein condensate.
AB  - A pendulum prepared perfectly inverted and motionless is a prototype of unstable
      equilibrium and corresponds to an unstable hyperbolic fixed point in the
      dynamical phase space. Here, we measure the non-equilibrium dynamics of a spin-1
      Bose-Einstein condensate initialized as a minimum uncertainty spin-nematic state
      to a hyperbolic fixed point of the phase space. Quantum fluctuations lead to non
      linear spin evolution along a separatrix and non-Gaussian probability
      distributions that are measured to be in good agreement with exact quantum
      calculations up to 0.25 s. At longer times, atomic loss due to the finite
      lifetime of the condensate leads to larger spin oscillation amplitudes, as orbits
      depart from the separatrix. This demonstrates how decoherence of a many-body
      system can result in apparent coherent behaviour. This experiment provides new
      avenues for studying macroscopic spin systems in the quantum limit and for
      investigations of important topics in non-equilibrium quantum dynamics.

PMID- 23132018
TI  - Sos-mediated cross-activation of wild-type Ras by oncogenic Ras is essential for
      tumorigenesis.
AB  - Mammalian cells contain three closely related ras genes, H-ras, K-ras and N-ras.
      Although in a given tumour type, oncogenic mutations are selectively observed in
      only one of the ras genes, the acquisition of the transformed phenotype has been
      shown to require the contribution of the normal products of the other ras genes.
      Here we demonstrate that oncogenic K-Ras promotes the activation of wild-type H-
      and N-Ras. This activation is mediated by oncogenic K-Ras-dependent allosteric
      stimulation of Sos and confers a growth advantage to oncogenic K-Ras harbouring
      cancer cells. These findings underscore the complementary functions of oncogenic
      and wild-type Ras in tumour cells and identify a potential new targeting strategy
      for Ras-driven tumours.

PMID- 23132020
TI  - Carrier multiplication in semiconductor nanocrystals detected by energy transfer
      to organic dye molecules.
AB  - Carrier multiplication describes an interesting optical phenomenon in
      semiconductors whereby more than one electron-hole pair, or exciton, can be
      simultaneously generated upon absorption of a single high-energy photon. So far,
      it has been highly debated whether the carrier multiplication efficiency is
      enhanced in semiconductor nanocrystals as compared with their bulk counterpart.
      The controversy arises from the fact that the ultrafast optical methods currently
      used need to correctly account for the false contribution of charged excitons to
      the carrier multiplication signals. Here we show that this charged exciton issue
      can be resolved in an energy transfer system, where biexcitons generated in the
      donor nanocrystals are transferred to the acceptor dyes, leading to an enhanced
      fluorescence from the latter. With the biexciton Auger and energy transfer
      lifetime measurements, an average carrier multiplication efficiency of ~17.1% can
      be roughly estimated in CdSe nanocrystals when the excitation photon energy is
      ~2.46 times of their energy gap.

PMID- 23132021
TI  - Magnetic and electric coherence in forward- and back-scattered electromagnetic
      waves by a single dielectric subwavelength sphere.
AB  - Magnetodielectric small spheres present unusual electromagnetic scattering
      features, theoretically predicted a few decades ago. However, achieving such
      behaviour has remained elusive, due to the non-magnetic character of natural
      optical materials or the difficulty in obtaining low-loss highly permeable
      magnetic materials in the gigahertz regime. Here we present unambiguous
      experimental evidence that a single low-loss dielectric subwavelength sphere of
      moderate refractive index (n=4 like some semiconductors at near-infrared)
      radiates fields identical to those from equal amplitude crossed electric and
      magnetic dipoles, and indistinguishable from those of ideal magnetodielectric
      spheres. The measured scattering radiation patterns and degree of linear
      polarization (3-9 GHz/33-100 mm range) show that, by appropriately tuning the
      a/lambda ratio, zero-backward ('Huygens' source) or almost zero-forward
      ('Huygens' reflector) radiated power can be obtained. These Kerker scattering
      conditions only depend on a/lambda. Our results open new technological challenges
      from nano- and micro-photonics to science and engineering of antennas,
      metamaterials and electromagnetic devices.

PMID- 23132023
TI  - Bright e-Paper by transport of ink through a white electrofluidic imaging film.
AB  - Many of the highest performance approaches for electronic paper use voltage to
      reveal or hide dark pigments or dyes over a white pixel surface, and the
      reflectance of white pixels is lower than in real paper because the dark pigments
      or dyes can never be fully removed from the visible pixel area. Here, we
      introduce a re-designed approach for electronic paper that transposes coloured
      ink in front of or behind a white microfluidic film. Pixels can provide >90%
      reflective area and have demonstrated <15 ms switching for 150 pixels-per-inch
      resolution. This new approach is also the first of its kind for electrowetting
      style displays by allowing non-aligned lamination fabrication, and is the first
      ever colourant-transposing pixel that eliminates the need for ink
      microencapsulation or pixel borders.

PMID- 23132024
TI  - Experimental demonstration of quantum digital signatures using phase-encoded
      coherent states of light.
AB  - Digital signatures are frequently used in data transfer to prevent impersonation,
      repudiation and message tampering. Currently used classical digital signature
      schemes rely on public key encryption techniques, where the complexity of so
      called 'one-way' mathematical functions is used to provide security over
      sufficiently long timescales. No mathematical proofs are known for the long-term
      security of such techniques. Quantum digital signatures offer a means of sending
      a message, which cannot be forged or repudiated, with security verified by
      information-theoretical limits and quantum mechanics. Here we demonstrate an
      experimental system, which distributes quantum signatures from one sender to two
      receivers and enables message sending ensured against forging and repudiation.
      Additionally, we analyse the security of the system in some typical scenarios.
      Our system is based on the interference of phase-encoded coherent states of light
      and our implementation utilizes polarization-maintaining optical fibre and
      photons with a wavelength of 850 nm.

PMID- 23132022
TI  - Opposing regulation of dopaminergic activity and exploratory motor behavior by
      forebrain and brainstem cholinergic circuits.
AB  - Dopamine transmission is critical for exploratory motor behaviour. A key
      regulator is acetylcholine; forebrain acetylcholine regulates striatal dopamine
      release, whereas brainstem cholinergic inputs regulate the transition of dopamine
      neurons from tonic to burst firing modes. How these sources of cholinergic
      activity combine to control dopamine efflux and exploratory motor behaviour is
      unclear. Here we show that mice lacking total forebrain acetylcholine exhibit
      enhanced frequency-dependent striatal dopamine release and are hyperactive in a
      novel environment, whereas mice lacking rostral brainstem acetylcholine are
      hypoactive. Exploratory motor behaviour is normalized by the removal of both
      cholinergic sources. Involvement of dopamine in the exploratory motor phenotypes
      observed in these mutants is indicated by their altered sensitivity to the
      dopamine D2 receptor antagonist raclopride. These results support a model in
      which forebrain and brainstem cholinergic systems act in tandem to regulate
      striatal dopamine signalling for proper control of motor activity.

PMID- 23132025
TI  - A hybrid CMOS-imager with a solution-processable polymer as photoactive layer.
AB  - The solution-processability of organic photodetectors allows a straightforward
      combination with other materials, including inorganic ones, without increasing
      cost and process complexity significantly compared with conventional crystalline
      semiconductors. Although the optoelectronic performance of these organic devices
      does not outmatch their inorganic counterparts, there are certain applications
      exploiting the benefit of the solution-processability. Here we demonstrate that
      the small pixel fill factor of present complementary metal oxide semiconductor
      imagers, decreasing the light sensitivity, can be increased up to 100% by
      replacing silicon photodiodes with an organic photoactive layer deposited with a
      simple low-cost spray-coating process. By performing a full optoelectronic
      characterization on this first solution-processable hybrid complementary metal
      oxide semiconductor-imager, including the first reported observation of different
      noise types in organic photodiodes, we demonstrate the suitability of this novel
      device for imaging. Furthermore, by integrating monolithically different organic
      materials to the chip, we show the cost-effective portability of the hybrid
      concept to different wavelength regions.

PMID- 23132026
TI  - Simple push coating of polymer thin-film transistors.
AB  - Solution processibility is a unique advantage of organic semiconductors,
      permitting the low-cost production of flexible electronics under ambient
      conditions. However, the solution affinity to substrate surfaces remains a
      serious dilemma; liquid manipulation is more difficult on highly hydrophobic
      surfaces, but the use of such surfaces is indispensable for improving device
      characteristics. Here we demonstrate a simple technique, which we call 'push
      coating', to produce uniform large-area semiconducting polymer films over a
      hydrophobic surface with eliminating material loss. We utilize a
      poly(dimethylsiloxane)-based trilayer stamp whose conformal contact with the
      substrate enables capillarity-induced wetting of the surface. Films are formed
      through solvent sorption and retention in the stamp, allowing the stamp to be
      peeled perfectly from the film. The planar film formation on hydrophobic surfaces
      also enables subsequent fine film patterning. The technique improves the
      crystallinity and field-effect mobility of stamped semiconductor films,
      constituting a major step towards flexible electronics production.

PMID- 23132027
TI  - A general method for the large-scale synthesis of uniform ultrathin metal
      sulphide nanocrystals.
AB  - Ultrathin metal sulphide nanomaterials exhibit many unique properties, and are
      thus attractive materials for numerous applications. However, the high-yield,
      large-scale synthesis of well-defined ultrathin metal sulphide nanostructures by
      a general and facile wet-chemical method is yet to be realized. Here we report a
      universal soft colloidal templating strategy for the synthesis of high-quality
      ultrathin metal sulphide nanocrystals, that is 3.2 nm-thick hexagonal CuS
      nanosheets, 1.8 nm-diameter hexagonal ZnS nanowires, 1.2 nm-diameter orthorhombic
      Bi(2)S(3) nanowires and 1.8 nm-diameter orthorhombic Sb(2)S(3) nanowires. As a
      proof of concept, the ultrathin CuS nanosheets are used to fabricate an electrode
      for a lithium-ion battery, which exhibits a large capacity and good cycling
      stability, even after 360 cycles. Furthermore, high-yield, gram-scale production
      of these ultrathin metal sulphide nanomaterials has been achieved (~100%, without
      size-sorting process). Our method could be broadly applicable for the high-yield
      production of novel ultrathin nanostructures with great promise for various
      applications.

PMID- 23132029
TI  - [Classification of intrahepatic cholangiocarcinoma based on recent progress and
      new proposal].

PMID- 23132028
TI  - One-piece micropumps from liquid crystalline core-shell particles.
AB  - Responsive polymers are low-cost, light weight and flexible, and thus an
      attractive class of materials for the integration into micromechanical and lab-on
      chip systems. Triggered by external stimuli, liquid crystalline elastomers are
      able to perform mechanical motion and can be utilized as microactuators. Here we
      present the fabrication of one-piece micropumps from liquid crystalline core
      shell elastomer particles via a microfluidic double-emulsion process, the
      continuous nature of which enables a low-cost and rapid production. The liquid
      crystalline elastomer shell contains a liquid core, which is reversibly pumped
      into and out of the particle by actuation of the liquid crystalline shell in a
      jellyfish-like motion. The liquid crystalline elastomer shells have the potential
      to be integrated into a microfluidic system as micropumps that do not require
      additional components, except passive channel connectors and a trigger for
      actuation. This renders elaborate and high-cost micromachining techniques, which
      are otherwise required for obtaining microstructures with pump function,
      unnecessary.

PMID- 23132030
TI  - [Intrahepatic cholangiocarcinoma associated with viral hepatitis].

PMID- 23132031
TI  - [Clinical impact of PET/CT on the management of patients with intrahepatic
      cholangiocarcinoma].

PMID- 23132032
TI  - [Surgical treatment of intrahepatic cholangiocarcinoma based on the macroscopic
      subtype].

PMID- 23132033
TI  - [The progress of chemotherapy for intrahepatic cholangiocarcinoma].

PMID- 23132034
TI  - [A case of esophageal endocrine cell carcinoma with multiple liver metastases
      that had a complete response to multidisciplinary therapy].
AB  - A 71-year-old man was admitted to our hospital because of dysphagia, and primary
      endocrine cell carcinoma of the esophagus with multiple liver metastases was
      diagnosed. After 6 courses of CPT-11+CDDP combination chemotherapy, the liver
      metastases disappeared, although the esophageal squamous cell carcinoma component
      remained. Radiation therapy was added to treat the residual esophageal tumor, and
      a complete response was obtained. This case seems to suggest that
      multidisciplinary therapy, including chemotherapy, may be effective for treating
      esophageal endocrine cell carcinoma with other types of organ metastasis.

PMID- 23132035
TI  - [A case of diffuse cystic malformation in which submucosal tumor-like advanced
      gastric cancer was identified during 10-year follow-up].
AB  - A 66-year-old man with giant gastric folds had been followed up since February
      2000. In March 2010, a submucosal tumor of 35mm was identified with endoscopy and
      a low echoic mass was identified with endoscopic ultrasonography. After
      histologic diagnosis by endosonography-guided fine needle aspiration biopsy, he
      underwent a total gastrectomy. Histologic examination of the resected specimen
      revealed a tumor 20mm in diameter consisting of well-to-moderately differentiated
      tubular adenocarcinoma in the thickened wall of the gastric greater curvature,
      which contained small cystic lesions in the lamina propria. Immunohistochemical
      staining showed thick gastric wall consisting of not only multiple cysts but also
      smooth muscle, elastic and collagen fibers. The histologic diagnosis was advanced
      gastric cancer accompanied by diffuse cystic malformation (DCM). Although it is a
      rare condition, DCM should be considered in the differential diagnosis of giant
      gastric folds and as a pre-cancerous lesion.

PMID- 23132036
TI  - [A case of nonsurgical pneumoperitoneum associated with the incomplete type of
      intestinal Behcet disease].
AB  - A 58-year-old man was admitted with fever and arthralgia. He had some symptoms
      suggesting the incomplete type of Behcet disease, and a routine chest X-ray films
      showed the presence of massive pneumoperitoneum (PP). Exploratory laparotomy
      revealed no evidence of gastrointestinal perforation or peritonitis. Thus, we
      initially diagnosed it as idiopathic PP. However a 2*1-mm induration located on
      the antimesentric side of the ileum 50cm proximal to the ileocecal valve. The
      wedge-shaped pathological specimen showed ulcer perforation and its restoration.
      Finally we concluded it to be nonsurgical PP. This case provides significant
      information on the etiology of idiopathic PP.

PMID- 23132037
TI  - [A metastatic rectal carcinoma originating from the uterine cervix].
AB  - A 40-year-old woman underwent radical hysterectomy and postoperative radiotherapy
      for uterine cervical squamous cell carcinoma (SCC) 6 years previously. She was
      referred to our department for the treatment of a rectal lesion located in the
      posterior wall approximately 8 cm from the anal verge. She underwent low anterior
      resection because the lesion was diagnosed as SCC by preoperative endoscopic
      biopsy. Pathological examination of the resected lesion demonstrated a 3 * 3-cm
      solid tumor expanding mainly in the muscularis propria layer and infiltrating the
      mucosal layer without lymph node involvement. Moreover, it was diagnosed as
      metastatic SCC from the uterine cervical tumor. No recurrence has been detected
      over 5 years after resection. The prognosis of SCC of the rectum without lymph
      node metastasis has been considered similar to that of node-negative
      adenocarcinoma of the rectum. Thus, if there is no distant metastasis and/or
      peritoneal dissemination, aggressive surgical resection should be performed to
      ensure a good prognosis.

PMID- 23132038
TI  - [Long-term survival of a case of rectal cancer discovered after resection of a
      single brain metastasis].
AB  - A woman in her fifties had shown a decline of orientation before admission. She
      had a tumor in the left frontal lobe. The solitary tumor was resected. Rectal
      cancer was discovered after that, and she underwent the Hartmann procedure. The
      final diagnosis was metastatic brain carcinoma from primary rectal cancer.
      Subsequently recurrence of brain metastasis was diagnosed, and gamma knife
      radiosurgery was performed. She then received adjuvant chemotherapy for about 1
      year. Since the gamma knife treatment, she has been followed up without any
      further evidence of recurrence. We believe that if solitary brain metastases are
      found early adjuvant therapy should be performed, which should prolong survival.

PMID- 23132039
TI  - [A case of enteric muco-submucosal elongated polyp].
AB  - A woman in her seventies was admitted because of black stool.
      Esophagogastroduodenoscopy and colonoscopy revealed no bleeding lesions. Balloon
      endoscopy showed a long and slender polyp. The polyp was covered with normal
      mucosa and accompanied with ulcerations. The long polypoid lesion was found to be
      located in the duodenojejunal flexure by a small bowel series. We performed
      endoscopic polypectomy. The polyp was composed of edematous mucosa and submucosa
      with dilated blood vessels and lymphangiectasia. The histologic findings of
      resected specimen were compatible with colonic muco-submucosal elongated polyp.
      The polyp was considered to be classified as enteric muco-submucosal elongated
      polyp.

PMID- 23132040
TI  - [A case of hepatocellular carcinoma with multiple lymph node metastases detected
      by FDG-PET].
AB  - We report a case of hepatocellular carcinoma (HCC) with multiple lymph node (LN)
      metastases. A 68-year-old man underwent hepatectomy at our hospital. Intrahepatic
      recurrence and swelling of multiple LNs were detected by enhanced CT 21 months
      later. FDG-PET was positive for multiple swollen LNs, but all were negative for
      the intrahepatic recurrences. Biopsy of para-aortic LNs was revealed LN
      metastases from HCC. Immunohistochemically, the LN metastases were composed of
      poorly differentiated HCC. The sensitivity of FDG-PET in patients with HCC varies
      in relation to degree of differentiation and decreased FDG uptake must be noted.

PMID- 23132042
TI  - Palladium, iridium and ruthenium complexes with acyclic imino-N-heterocyclic
      carbenes and their application in aqua-phase Suzuki-Miyaura cross-coupling
      reaction and transfer hydrogenation.
AB  - Palladium (4a-4c), iridium (5a-5c) and ruthenium (6a-6c) complexes have been
      prepared by in situ transmetalation from the corresponding silver complexes of
      acyclic imino-functionalized imidazolium chlorides [1-(Me)-imidazolium-3-{C(p
      CH(3)-Ph)=N(Ar)}]Cl (3) (Ar = 2,4,6-trimethylphenyl (3a), 2,6-diisopropylphenyl
      (3b) and phenyl (3c)) with [Pd(COD)Cl(2)], [Cp*IrCl(2)](2) or [Ru(p
      cymene)Cl(2)](2), respectively. Iridium and ruthenium complexes, 5a[PF(6)]
      5c[PF(6)], 6a[PF(6)]-6c[PF(6)], 6c[BF(4)], 6c[BPh(4)] and 6c[NTf(2)], were
      obtained directly from 5a-5c and 6a-6c through an anion-exchange process with
      KPF(6), NaBF(4), NaBPh(4) and LiNTf(2) (bis(trifluoromethylsulfonyl)imide
      lithium), respectively. All complexes were characterized by FT-IR, (1)H and (13)C
      NMR spectroscopy and elemental analysis. Crystal structures of 4a, 5a and
      6c[NTf(2)], and show that five-membered chelate ring is formed in these complexes
      by the coordination of the carbene carbon and the imino nitrogen atom, and the
      latter two are cationic compounds with Cl(-) and NTf(2)(-) as counteranion
      respectively. The catalytic performance of Pd complexes for Suzuki-Miyaura cross
      coupling reactions in pure water and Ir and Ru complexes for transfer
      hydrogenation of ketones and imines was tested in a wide scope of substrates. Pd
      complex 4b with the largest steric hinder exhibited the best performance to gain
      moderate to excellent yields on catalyzing Suzuki-Miyaura cross-coupling of aryl
      chlorides and arylboronic acids in water. While in transfer hydrogenation of
      various ketones, all the Ir and Ru complexes were effective with good to
      excellent yields. Among all these complexes, 6c[PF(6)] was found most effective,
      and moderate yields could be obtained even in the transfer hydrogenation of
      imines. Moreover, different counteranions of Ru complexes are influential on
      catalyzing the transfer hydrogenation, with the sequence of PF(6)(-) ~ BF(4)(-) >
      BPh(4)(-) > Cl(-) > NTf(2)(-).

PMID- 23132041
TI  - [Mucoepidermoid carcinoma of the intrahepatic bile duct with metastasis to the
      cranial skin].
AB  - Mucoepidermoid carcinoma of the intrahepatic bile duct is a rare variant of
      cholangiocarcinoma: it is composed of mucus-secreting squamous cells and
      glandular cells within the same nests. This tumor is very aggressive, with high
      grade malignancy, and has a poor prognosis. In the international literature, only
      17 cases of mucoepidermoid carcinoma originating in the hepatic bile duct system
      have been reported until now. We report an autopsy case of mucoepidermoid
      carcinoma of the intrahepatic bile duct with metastasis to the cranial skin in a
      Japanese man who was more than 70 years old. This cancer metastasizes to many
      organs, but skin metastasis is extremely rare.

PMID- 23132043
TI  - The risks associated with aprotinin use: a retrospective study of cardiac cases
      in Nova Scotia.
AB  - PURPOSE: In light of the concerns about the safety of aprotinin, we wanted to
      determine if aprotinin use during cardiac surgery was associated with an
      increased risk of mortality and morbidity compared with the use of tranexamic
      acid (TXA). We hypothesized that use of aprotinin is associated with a higher
      risk of adverse outcomes than use of TXA in our patient population. METHODS: In
      this retrospective study at a single surgical centre, we examined primary in
      hospital outcomes of postoperative mortality, new acute renal failure, and
      perioperative blood transfusion, and we also investigated secondary outcomes of
      stroke, infection, and prolonged stay in the intensive care unit (ICU). The
      effect of the type of antifibrinolytic on outcome was evaluated for aprotinin
      cases matched 1:1 with TXA cases using propensity score. RESULTS: This study
      included 3,340 patients who received antifibrinolytics during cardiac surgery
      (376 patients received aprotinin and 2,964 patients received TXA). Patients who
      received aprotinin were more often elderly and female; they were more commonly
      presented with congestive heart failure, atrial fibrillation, renal failure, and
      lower hemoglobin, and they underwent complex and/or urgent surgery. In the
      matched sample, in-hospital mortality was significantly higher in the aprotinin
      group (10.9%) compared with the TXA group (5.9%), and ICU stay >72 hr was
      significantly increased in the aprotinin group (30.0%) compared with the TXA
      group (21.7%). There was no significant difference in blood product
      administration between the two groups. CONCLUSIONS: Aprotinin was associated with
      an increased risk of in-hospital mortality and morbidity following cardiac
      surgery, and aprotinin was not associated with a decrease in blood product
      requirements. Continued use of aprotinin in cardiac surgery should follow careful
      consideration, weighing the demonstrated risks and potential advantages compared
      with other TXA.

PMID- 23132044
TI  - Relative potency of pregabalin, gabapentin, and morphine in a mouse model of
      visceral pain.
AB  - PURPOSE: Pregabalin is probably more effective than prototype gabapentin in
      different kinds of pain treatments. This study was performed to compare the
      potency of gabapentin, pregabalin, and morphine in a well-established model of
      visceral pain. METHODS: The number of abdominal contractions was counted for 30
      min in adult male mice that received different doses of pregabalin, gabapentin,
      morphine, or placebo intraperitoneally 30 min before receiving 0.6% acetic acid
      10 mL.kg(-1).The antinociceptive effect of each drug dose was determined as a
      percentage of the reduction in the number of acetic acid-induced writhes. The
      effective doses, for 20%, 50%, and 80% response (ED(20), ED(50), and ED(80),
      respectively), of each drug were calculated using least squares linear regression
      analysis, and then dose-response curves were compared. RESULTS: Pregabalin,
      gabapentin, and morphine produced a linear dose-dependent antinociceptive effect
      (coefficient of determination [r(2)] > 0.9). No difference was observed between
      slopes of dose-response curves. The ED(50) estimates (95% confidence interval)
      for pregabalin, gabapentin, and morphine were 17.1 (12.9 to 22.1) mg.kg(-1), 87.1
      (45.8 to 129.8) mg.kg(-1), and 0.2 (0.1 to 0.3) mg.kg(-1), respectively.
      CONCLUSION: In this animal model of visceral pain, all three drugs exhibited
      parallel dose-response curves. Pregabalin had five times the potency of
      gabapentin and 1/85(th) the potency of morphine. Similar potency ratios may apply
      in clinical practice. Despite some limitations of animal studies, this model
      could be useful for comparing new analgesics in visceral pain treatment.

PMID- 23132045
TI  - The scavenging of volatile anesthetic agents in the cardiovascular intensive care
      unit environment: a technical report.
AB  - PURPOSE: The use of volatile-based sedation within critical care environments has
      been limited by difficulties of drug administration and safety concerns over
      environment pollution and staff exposure in an intensive care unit (ICU) with no
      scavenging. The aim of this study was to develop a simple scavenging system to be
      used with the Anesthesia Conserving Device (AnaConDa((r))) and to determine
      whether or not ambient concentrations of residual anesthetic are within current
      acceptable limits. TECHNICAL FEATURES: The scavenging system consists of two
      Deltasorb((r)) canisters attached to the ICU ventilator in series. AnaConDa is a
      miniature vaporizer designed to provide volatile-based sedation within an ICU.
      The first ten patients recruited into a larger randomized trial assessing
      outcomes after elective coronary graft bypass surgery were sedated within the
      cardiac ICU using either isoflurane or sevoflurane. Sedation was guided by the
      Sedation Agitation Scale, resulting in an end-tidal minimum anesthetic
      concentration of volatile agent ranging from 0.1-0.3. At one hour post ICU
      admission, infrared photometric analysis was used to assess environmental
      contamination at four points along the ventilator circuit and scavenging system
      and around the patient's head. All measurements taken within the patient's room
      were below 1 part per million, which satisfies criteria for occupational
      exposure. CONCLUSIONS: This study shows that volatile agents can be administered
      safely within critical care settings using a simple scavenging system. Our
      scavenging system used in conjunction with the AnaConDa device reduced the
      concentration of environmental contamination to a level that is acceptable to
      Canadian standards and standards in most Western countries and thus conforms to
      international safety standards. The related clinical trial was registered at
      www.clinicaltrials.gov (NCT01151254).

PMID- 23132046
TI  - Cesarean delivery in a parturient with an anterior mediastinal mass.

PMID- 23132047
TI  - Measuring aortic valve coaptation surface area using three-dimensional
      transesophageal echocardiography.
AB  - BACKGROUND: As aortic valve (AV) repairs become more sophisticated, surgeons need
      increasingly detailed information about the structure and function of this valve.
      Unlike two-dimensional transesophageal echocardiography (2D-TEE), using three
      dimensional (3D)-TEE makes it possible to image the entire AV. We hypothesized
      that measuring coaptation surface area (CoapSA) would be feasible and
      reproducible, and CoapSA would decrease in patients with aortic insufficiency.
      METHODS: We developed a new technique to calculate the AV-CoapSA using 3D-TEE. We
      measured the coaptation surfaces between the right coronary cusp/left coronary
      cusp, right coronary cusp/non-coronary cusp, and left coronary cusp/non-coronary
      cusp in ten normal AVs and ten AVs with moderate-severe aortic insufficiency
      (AI). Since computer models have previously shown that CoapSA is trapezoidal, we
      used the formula: trapezoid area = length * (medial coaptation height + lateral
      coaptation height)/2. The total CoapSA was calculated by adding all three areas.
      To adjust for valve size, we indexed the value to the diameter of the ventricular
      aortic junction (VAJ). Measurements were performed by two observers. RESULTS: The
      intra-observer correlation was 0.84 for one observer (P < 0.0001) and 0.93 for
      the other (P < 0.0001). The inter-observer correlation was 0.87 (P < 0.0001). In
      normal valves, the CoapSA [mean total (standard deviation)] was significantly
      greater than in the insufficient valves [1.61 (0.31) cm(2) vs 1.03 (0.22) cm(2),
      respectively; P < 0.001]. After indexing for the VAJ diameter, the total CoapSA
      remained significantly greater in normal valves than in insufficient valves.
      CONCLUSION: In this proof of concept study, we present a new and innovative
      technique to measure AV-CoapSA using 3D-TEE. It is reproducible and shows
      decreased CoapSA in patients with AI. Coaptation surface area may provide insight
      into mechanisms of AI and may have predictive value following AV repair.

PMID- 23132048
TI  - Genetic dissection of developmental behavior of grain weight in wheat under
      diverse temperature and water regimes.
AB  - As a quantitatively inherited trait related to high yield potential, grain weight
      (GW) development in wheat is constrained by abiotic stresses such as limited
      water supply and high temperature. Data from a doubled haploid population,
      derived from a cross of (Hanxuan 10 * Lumai 14), grown in four environments were
      used to explore the genetic basis of GW developmental behavior in unconditional
      and conditional quantitative trait locus (QTL) analyses using a mixed linear
      model. Thirty additive QTLs and 41 pairs of epistatic QTLs were detected, and
      were more frequently observed on chromosomes 1B, 2A, 2D, 4A, 4B and 7B. No single
      QTL was continually active during all stages or periods of grain growth. The QTLs
      with additive effects (A-QTLs) expressed in the period S1|S0 (the period from the
      flowering to the seventh day after) formed a foundation for GW development. GW
      development at these stages can be used as an index for screening superior
      genotypes under diverse abiotic stresses in a wheat breeding program. One QTL,
      i.e. Qgw.cgb-6A.2, showed high adaptability for water-limited and heat-stress
      environments. Many A-QTLs interacted with more than one other QTL in the two
      genetic models, such as Qgw.cgb-4B.2 interacted with five QTLs, showing that the
      genetic architecture underlying GW development involves a collective expression
      of genes with additive and epistatic effects.

PMID- 23132049
TI  - Sexuality after hysterectomy at University of Jordan Hospital: a teaching
      hospital experience.
AB  - PURPOSE: This research concentrates on evaluating the sexual activity of the
      patients after having hysterectomy for benign disorders. SETTING: This analysis
      took place at the University of Jordan hospital. MATERIAL AND METHODS: The
      retrospective record was reviewed for over 2 years (from January 2008 to January
      2010). The sample of study included a total number of 124 patients with benign
      disorders who underwent hysterectomy. The sexual life parameters indicate that 93
      patients (75 %) felt general improvement in their performance, while 14 patients
      (11.3 %) complained of having suffered bad performance, 6 patients (4.8 %)
      noticed no changes, and 11 patients (8.9 %) did not provide any comment. As for
      the partner's sexual function (as relayed by the patients themselves), 69
      patients (55.6 %) felt improvements in their performance and 23 (18.5 %)
      commented that their partners had bad performance, while 18 patients (14.5 %)
      noticed no changes and 14 (11.3 %) did not provide any comment. Patients were
      interviewed by the operating physician each of whom was subjected to an average
      of half an hour verbal interview after obtaining the prior written consent of the
      patient. Questionnaire forms were used to record the answers given by each
      patient. The interview data recorded in the questionnaires were analyzed.
      CONCLUSION: The result of these analyses significantly indicated that sexual
      function is a major cause of women's concern for scheduled hysterectomy. That is
      because they were influenced by both physiological and psychological factors.
      Even though the analysis results implied that there was a sizeable minority who
      evidently suffered a considerably worse outcome, it was recognized that
      hysterectomy leads to improvement in sexual function and health for the majority
      of women. Therefore, it is important to spread awareness among women and let them
      know that most probably they will neither lose their sexual desire after
      hysterectomy, nor they will lose their feminine shape or style.

PMID- 23132050
TI  - Cesarean section rate differences by migration indicators.
AB  - PURPOSE: To answer the question: are there differences in cesarean section rates
      among childbearing women in Canada according to selected migration indicators?
      METHODS: Secondary analyses of 3,500 low-risk women who had given birth between
      January 2003 and April 2004 in one of ten hospitals in the major Canadian migrant
      receiving cities (Montreal, Toronto, Vancouver) were conducted. Women were
      categorized as non-refugee immigrant, asylum seeker, refugee, or Canadian-born
      and by source country world region. Stratified analyses were performed. RESULTS:
      Cesarean section rates differed by migration status for women from two source
      regions: South East and Central Asia (non-refugee immigrants 26.0 %, asylum
      seekers 28.6 %, refugees 56.7 %, p = 0.001) and Latin America (non-refugee
      immigrants 37.7 %, asylum seekers 25.6 %, refugees 10.5 %, p = 0.05). Of these,
      low-risk refugee women who had migrated to Canada from South East and Central
      Asia experienced excess cesarean sections, while refugees from Latin America
      experienced fewer, compared to Canadian-born (25.4 %, 95 % CI 23.8-27.3).
      Cesarean section rates of African women were consistently high (31-33 %)
      irrespective of their migration status but were not statistically different from
      Canadian-born women. Although it did not reach statistical significance, risk for
      cesarean sections also differed by time since migration (<=2 years 29.8 %, >2
      years 47.2 %). CONCLUSION: Migration status, source region, and time since
      migration are informative migration indicators for cesarean section risk.

PMID- 23132051
TI  - An achieved live birth following five-time serial stillbirth by serious Rh
      alloimmunization.

PMID- 23132052
TI  - Introduction to electron crystallography.
AB  - From the earliest work on regular arrays in negative stain, electron
      crystallography has contributed greatly to our understanding of the structure and
      function of biological macromolecules. The development of electron cryo
      microscopy (cryo-EM) then lead to the first groundbreaking atomic models of the
      membrane proteins bacteriorhodopsin and light harvesting complex II within lipid
      bilayers. Key contributions towards cryo-EM and electron crystallography methods
      included specimen preparation and vitrification, liquid-helium cooling, data
      collection, and image processing. These methods are now applied almost routinely
      to both membrane and soluble proteins. Here we outline the advances and the
      breakthroughs that paved the way towards high-resolution structures by electron
      crystallography, both in terms of methods development and biological milestones.

PMID- 23132053
TI  - Practical aspects in expression and purification of membrane proteins for
      structural analysis.
AB  - A surge of membrane protein structures in the last few years can be attributed to
      advances in technologies starting at the level of genomes, to highly efficient
      expression systems, stabilizing conformational flexibility, automation of
      crystallization and data collection for screening large numbers of crystals and
      the microfocus beam lines at synchrotrons. The substantial medical importance of
      many membrane proteins provides a strong incentive to understand them at the
      molecular level. It is becoming obvious that the major bottleneck in many of the
      membrane projects is obtaining sufficient amount of stable functional proteins in
      a detergent micelle for structural studies. Naturally, large effort has been
      spent on optimizing and advancing multiple expression systems and purification
      strategies that have started to yield sufficient protein and structures. We
      describe in this chapter protocols to refold membrane proteins from inclusion
      bodies, purification from inner membranes of Escherichia coli and from mammalian
      cell lines.

PMID- 23132054
TI  - Two-dimensional crystallization of membrane proteins by reconstitution through
      dialysis.
AB  - Studies of membrane proteins by two-dimensional (2D) crystallization and electron
      crystallography have provided crucial information on the structure and function
      of a rapidly growing number of these intricate proteins within a close-to-native
      lipid bilayer. Here we provide protocols for planning and executing 2D
      crystallization trials by detergent removal through dialysis, including the
      preparation of phospholipids and the dialysis setup. General factors to be
      considered, such as the protein preparation, solubilizing detergent, lipid for
      reconstitution, and buffer conditions are discussed. Several 2D crystallization
      conditions are highlighted that have shown great promise to grow 2D crystals
      within a surprisingly short amount of time. Finally, conditions for optimizing
      order and size of 2D crystals are outlined.

PMID- 23132055
TI  - Monolayer two-dimensional crystallization of membrane proteins.
AB  - This method of two-dimensional crystallization of proteins on a lipid monolayer
      aims at producing 2D crystals of membrane proteins, which can provide structural
      information at high resolution by electron crystallography. A lipid monolayer is
      spread over the whole air-water interface of a drop, which provides a substrate
      for protein binding. The protein of interest is then adsorbed onto the lipid
      monolayer and forms a closely packed layer. The reconstitution step of the
      membrane protein into a lipid bilayer is realized by elimination of detergent.
      The combined effect of the elevated protein concentration, the alignment of the
      protein on the lipid monolayer, and the fluid monolayer film properties are
      conducive, in some cases, to the formation of 2D crystals. The use of locally
      fluorinated lipids in avoiding solubilization of the lipid monolayer by
      detergents is presented and discussed.

PMID- 23132057
TI  - Low dose techniques and cryo-electron microscopy.
AB  - Our understanding of subcellular structures has been greatly increased owing to
      electron microscopy, even though radiation damage of biological samples by the
      electron beam demanded staining techniques. Technological and instrumental
      advances of electron microscopy have, however, established various highly
      sophisticated techniques to study biological systems in their native states
      without staining and thus facilitated comprehension of rather intact structures
      of biological components. Among these techniques, electron crystallography is a
      well-established one to analyze membrane protein structures within lipid
      bilayers, without staining at close-to-physiological conditions. Structures of
      membrane proteins could be analyzed at resolutions better than 3A by electron
      crystallography due to techniques of low dose and cryo-electron microscopy (cryo
      EM). Here, recent cryo-EM technological and instrumental advances crucial to
      optimal data collection in electron crystallography are summarized as well as
      examples of structures of membrane proteins analyzed with the help of this
      method.

PMID- 23132056
TI  - Screening for two-dimensional crystals by transmission electron microscopy of
      negatively stained samples.
AB  - Structural studies of soluble and membrane proteins by electron crystallography
      include several critical steps. While the two-dimensional (2D) crystallization
      arguably may be described as the major bottleneck of electron crystallography,
      the screening by transmission electron microscopy (EM) to identify 2D crystals
      requires great care as well as practice. Both sample preparation and EM are
      skills that are relatively easily acquired, compared to the identification of the
      first ordered arrays. Added to this, membranes may have a variety of morphologies
      and sizes. Here we describe all steps involved in the screening for 2D crystals
      as well as the evaluation of samples.

PMID- 23132058
TI  - Grid preparation for cryo-electron microscopy.
AB  - Once 2D crystals suitable for electron crystallography have been obtained, grid
      preparation for cryo-EM is a critical step in obtaining high-resolution
      structural information. Specimens have to be prepared in a manner that prevents
      dehydration and disruption of the crystals in the vacuum of the electron
      microscope. Sugar embedding is an effective way to preserve specimens in the
      native and hydrated state. Preparation of almost perfectly flat specimens is
      another prerequisite. Imperfect specimen flatness is a crucial problem in the
      recording of images and diffraction patterns at higher tilt angles because it
      causes the blurring of spots perpendicular to the tilt axis. In this chapter, we
      describe the protocols of preparing 2D crystal specimen for electron
      crystallographical data collection. These protocols cover preparation of a flat
      carbon support film by sparkless carbon evaporation, sugar embedding using back
      injection, and the recently developed carbon sandwich technique.

PMID- 23132059
TI  - Recording high-resolution images of two-dimensional crystals of membrane
      proteins.
AB  - Principles underlying the recording of high-quality/resolution images of two
      dimensional crystals of membrane proteins are discussed in the context of
      instrumental conditions and operational procedures. A detailed example of low
      dose microscope settings is provided along with an overview of a program that
      implements a computer-aided data acquisition procedure.

PMID- 23132060
TI  - The collection of high-resolution electron diffraction data.
AB  - A number of atomic-resolution structures of membrane proteins (better than 3A
      resolution) have been determined recently by electron crystallography. While this
      technique was established more than 40 years ago, it is still in its infancy with
      regard to the two-dimensional (2D) crystallization, data collection, data
      analysis, and protein structure determination. In terms of data collection,
      electron crystallography encompasses both image acquisition and electron
      diffraction data collection. Other chapters in this volume outline protocols for
      image collection and analysis. This chapter, however, outlines detailed protocols
      for data collection by electron diffraction. These include microscope setup,
      electron diffraction data collection, and troubleshooting.

PMID- 23132061
TI  - Image processing of 2D crystal images.
AB  - Electron crystallography of membrane proteins uses cryo-transmission electron
      microscopy to image frozen-hydrated 2D crystals. The processing of recorded
      images exploits the periodic arrangement of the structures in the images to
      extract the amplitudes and phases of diffraction spots in Fourier space. However,
      image imperfections require a crystal unbending procedure to be applied to the
      image before evaluation in Fourier space. We here describe the process of 2D
      crystal image unbending, using the 2dx software system.

PMID- 23132062
TI  - Merging of image data in electron crystallography.
AB  - Electron crystallography of membrane proteins uses cryo-transmission electron
      microscopy to record images and diffraction patterns of frozen-hydrated 2D
      crystals. Each two-dimensional (2D) crystal is only imaged once, at one specific
      tilt angle, and the recorded images can be automatically processed with the
      2dx/MRC software package. Processed image data from non-tilted and tilted 2D
      crystals then need to be merged into a 3D reconstruction of the membrane protein
      structure. We here describe the process of the 3D merging, using the 2dx software
      system.

PMID- 23132063
TI  - Evaluation of electron crystallographic data from images of two-dimensional
      crystals.
AB  - In the past, various formats have been used to present data fidelity of electron
      crystallographic data from images of two-dimensional crystals. While each scheme
      provides some information about the data, not all schemes are equally useful for
      presenting data reliability. This brief chapter gives guidelines on how to look
      at datasets that are solely derived from images, and on how to summarize the data
      structure through graphical outputs that provide unbiased and detailed
      information about data quality. By the time of publication, the actual procedures
      described here will have been integrated into the 2dx package and therefore,
      these evaluation tools will be available at a "push of a button." Because of
      this, the chapter focuses on brief explanations for why certain ways of
      presenting data make more sense than others.

PMID- 23132064
TI  - Modeling, docking, and fitting of atomic structures to 3D maps from cryo-electron
      microscopy.
AB  - Electron microscopy (EM) and image analysis offer an effective approach for
      determining the three-dimensional structure of macromolecular complexes. The
      versatility of these methods means that molecular species not normally amenable
      to other structural methods, e.g., X-ray crystallography and NMR spectroscopy,
      can be analyzed. However, the resolution of EM structures is often too low to
      provide an atomic model directly by chain tracing. Instead, a combination of
      modeling and fitting can be an effective way to analyze the EM structure at an
      atomic level, thus allowing localization of subunits or evaluation of
      conformational changes. Here we describe the steps involved in this process:
      building a homology model, fitting this model to an EM map, and using
      computational methods for docking of additional domains to the model. As an
      example, we illustrate the methods using an integral membrane protein, CopA,
      which functions to pump copper across the membrane in an ATP-dependent manner. In
      this example, we build a homology model based on the published atomic coordinates
      for a related calcium pump from sarcoplasmic reticulum (SERCA). After fitting
      this homology model to a 17 A resolution EM map, computational software is used
      to dock a metal-binding domain (MBD) that is unique to the copper pump. Although
      this software identifies a number of plausible interfaces for docking, the
      constraints of the EM map steer us to select a unique solution. Thus, the synergy
      of these two methods allows us to describe both the location of the unknown MBD
      relative to the other cytoplasmic domains and the atomic details of the domain
      interface.

PMID- 23132065
TI  - Phasing electron diffraction data by molecular replacement: strategy for
      structure determination and refinement.
AB  - Electron crystallography is arguably the only electron cryomicroscopy (cryo EM)
      technique able to deliver atomic resolution data (better then 3 A) for membrane
      proteins embedded in a membrane. The progress in hardware improvements and sample
      preparation for diffraction analysis resulted in a number of recent examples
      where increasingly higher resolutions were achieved. Other chapters in this book
      detail the improvements in hardware and delve into the intricate art of sample
      preparation for microscopy and electron diffraction data collection and
      processing. In this chapter, we describe in detail the protocols for molecular
      replacement for electron diffraction studies. The use of a search model for
      phasing electron diffraction data essentially eliminates the need of acquiring
      image data rendering it immune to aberrations from drift and charging effects
      that effectively lower the attainable resolution.

PMID- 23132067
TI  - Automated grid handling and image acquisition for two-dimensional crystal
      screening.
AB  - Routine large-scale two-dimensional (2D) crystallization trials are good
      candidates for automation. For imaging the large number of grids prepared from 2D
      crystallization trials, a two-pass imaging protocol using Leginon and a grid
      handling robot is described. A manual target selection bridges the two imaging
      passes. The two passes can be combined into one if objects of interests at
      different stages of trials can be reliably found using automated methods.

PMID- 23132066
TI  - High-throughput methods for electron crystallography.
AB  - Membrane proteins play a tremendously important role in cell physiology and serve
      as a target for an increasing number of drugs. Structural information is key to
      understanding their function and for developing new strategies for combating
      disease. However, the complex physical chemistry associated with membrane
      proteins has made them more difficult to study than their soluble cousins.
      Electron crystallography has historically been a successful method for solving
      membrane protein structures and has the advantage of providing a native lipid
      environment for these proteins. Specifically, when membrane proteins form two
      dimensional arrays within a lipid bilayer, electron microscopy can be used to
      collect images and diffraction and the corresponding data can be combined to
      produce a three-dimensional reconstruction, which under favorable conditions can
      extend to atomic resolution. Like X-ray crystallography, the quality of the
      structures are very much dependent on the order and size of the crystals.
      However, unlike X-ray crystallography, high-throughput methods for screening
      crystallization trials for electron crystallography are not in general use. In
      this chapter, we describe two alternative methods for high-throughput screening
      of membrane protein crystallization within the lipid bilayer. The first method
      relies on the conventional use of dialysis for removing detergent and thus
      reconstituting the bilayer; an array of dialysis wells in the standard 96-well
      format allows the use of a liquid-handling robot and greatly increases
      throughput. The second method relies on titration of cyclodextrin as a chelating
      agent for detergent; a specialized pipetting robot has been designed not only to
      add cyclodextrin in a systematic way, but to use light scattering to monitor the
      reconstitution process. In addition, the use of liquid-handling robots for making
      negatively stained grids and methods for automatically imaging samples in the
      electron microscope are described.

PMID- 23132068
TI  - Automation of data acquisition in electron crystallography.
AB  - General considerations for using automation software for acquiring high
      resolution images of 2D crystals under low-dose conditions are presented.
      Protocol modifications specific to this application in Leginon are provided.

PMID- 23132070
TI  - Choice and maintenance of equipment for electron crystallography.
AB  - The choice of equipment for an electron crystallography laboratory will
      ultimately be determined by the available budget; nevertheless, the ideal lab
      will have two electron microscopes: a dedicated 300 kV cryo-EM with a field
      emission gun and a smaller LaB(6) machine for screening. The high-end machine
      should be equipped with photographic film or a very large CCD or CMOS camera for
      2D crystal data collection; the screening microscope needs a mid-size CCD for
      rapid evaluation of crystal samples. The microscope room installations should
      provide adequate space and a special environment that puts no restrictions on the
      collection of high-resolution data. Equipment for specimen preparation includes a
      carbon coater, glow discharge unit, light microscope, plunge freezer, and liquid
      nitrogen containers and storage dewars. When photographic film is to be used,
      additional requirements are a film desiccator, dark room, optical diffractometer,
      and a film scanner. Having the electron microscopes and ancillary equipment well
      maintained and always in optimum condition facilitates the production of high
      quality data.

PMID- 23132069
TI  - Automation of image processing in electron crystallography.
AB  - Electron crystallography of membrane proteins records images and diffraction
      patterns of frozen-hydrated two-dimensional (2D) crystals. To reconstruct the
      high-resolution three-dimensional (3D) structure of a membrane protein, a
      multitude of images of 2D crystals have to be processed. Certain processing steps
      are thereby similar for batches of images that were recorded under similar
      conditions. Here we describe how the 2dx software package can be used to automate
      the processing of 2D crystal images, and how the 2D and 3D merging results can be
      used to iteratively reprocess the images. While the processing of 2D crystal
      images has been fully automated, the merging process is still semi-manual.

PMID- 23132071
TI  - Future developments in instrumentation for electron crystallography.
AB  - Advances in instrumentation have proceeded at an impressive rate since the
      invention of the electron microscope. These advances have produced a continuous
      expansion of the capabilities and range of application of electron microscopy. In
      order to provide some insights on how continuing advances may enhance cryo
      electron microscopy and electron crystallography, we review some of the active
      areas of instrumentation development. There is strong momentum in areas including
      detectors, phase contrast devices, and aberration correctors that may have
      substantial impact on the productivity and expectations of electron
      crystallographers.

PMID- 23132073
TI  - Single particle electron microscopy.
AB  - Single particle electron microscopy is a versatile technique for the structural
      analysis of protein complexes in near-native conditions. While tremendous
      progress has been made during the past few decades in techniques for specimen
      preparation, imaging, and image analysis, the field is still in development. In
      the context of this volume on electron crystallography, the following chapter
      gives practical guidelines on how to begin single particle EM studies, including
      preparing specimens, selecting imaging conditions, and choosing which of the many
      approaches to image analysis are appropriate for a specific sample.

PMID- 23132074
TI  - Electron tomography of paracrystalline 2D arrays.
AB  - Paracrystalline arrays possess specific types of disorder that reduce the
      structural information as well as resolution when spatially averaged over
      repeating motifs. Electron tomography combined with motif classification and
      averaging can solve the heterogeneity problem and provide information on the
      structural elements that give rise to the disorder. This chapter describes
      procedures that would be used in a typical tomography application to identify and
      characterize a paracrystalline specimen. Particular emphasis is given to actively
      contracting insect flight muscle, a specimen with particularly difficult to
      characterize structural heterogeneity and 2D paracrystalline arrays of myosin-V,
      from which a particularly high resolution motif average was obtained. All aspects
      of the study are described including data collection, merging of micrographs to
      produce the tomogram, alignment to an invariant structural element,
      classification and averaging of heterogeneous structures, and reassembly of
      focused class averages into high signal-to-noise ratio representations of the
      original raw repeats. Particular emphasis is placed on limitations of the various
      processes to produce the final class averages.

PMID- 23132072
TI  - Tubular crystals and helical arrays: structural determination of HIV-1 capsid
      assemblies using iterative helical real-space reconstruction.
AB  - Helical structures are important in many different life forms and are well-suited
      for structural studies by cryo-EM. A unique feature of helical objects is that a
      single projection image contains all the views needed to perform a three
      dimensional (3D) crystallographic reconstruction. Here, we use HIV-1 capsid
      assemblies to illustrate the detailed approaches to obtain 3D density maps from
      helical objects. Mature HIV-1 particles contain a conical- or tubular-shaped
      capsid that encloses the viral RNA genome and performs essential functions in the
      virus life cycle. The capsid is composed of capsid protein (CA) oligomers which
      are helically arranged on the surface. The N-terminal domain (NTD) of CA is
      connected to its C-terminal domain (CTD) through a flexible hinge. Structural
      analysis of two- and three-dimensional crystals provided molecular models of the
      capsid protein (CA) and its oligomer forms. We determined the 3D density map of
      helically assembled HIV-1 CA hexamers at 16 A resolution using an iterative
      helical real-space reconstruction method. Docking of atomic models of CA-NTD and
      CA-CTD dimer into the electron density map indicated that the CTD dimer interface
      is retained in the assembled CA. Furthermore, molecular docking revealed an
      additional, novel CTD trimer interface.

PMID- 23132075
TI  - High-resolution imaging of 2D outer membrane protein F crystals by atomic force
      microscopy.
AB  - In this chapter the methodological bases are provided to achieve subnanometer
      resolution on two-dimensional (2D) membrane protein crystals by atomic force
      microscopy (AFM). This is outlined in detail with the example of AFM studies of
      the outer membrane protein F (OmpF) from the bacterium Escherichia coli (E.
      coli). We describe in detail the high-resolution imaging of 2D OmpF crystals in
      aqueous solution and under near-physiological conditions. The topographs of OmpF,
      and stylus effects and artifacts encountered when imaging by AFM are discussed.

PMID- 23132076
TI  - Determination of soluble and membrane protein structures by X-ray
      crystallography.
AB  - X-ray crystallography is a technique used to determine the atomic-detail
      structure of a biological macromolecule. The method relies on the ability to
      generate a three-dimensional crystal of a highly purified protein or nucleic acid
      for diffraction by X-rays. The extent of scattering of X-rays by the crystal
      determines the accuracy of the resulting structural model. Unlike electrons, X
      rays cannot be refocused after they have been scattered by their target. Thus,
      calculations are needed to reconstruct the image of the macromolecule that builds
      the crystal lattice. Tremendous advances over the past 60 years in recombinant
      expression and purification, crystal growth methods and equipment, X-ray sources,
      computer processing power, programs, and graphics have taken X-ray
      crystallography from a highly specialized field to one increasingly accessible to
      researchers in the biomedical sciences. In this chapter, we review the major
      concepts of macromolecular X-ray crystallography, focusing mainly on techniques
      for crystallizing soluble and membrane proteins, and provide a protocol for the
      crystallization of lysozyme as a model for the crystallization of other proteins.

PMID- 23132077
TI  - Solution nuclear magnetic resonance spectroscopy.
AB  - Solution nuclear magnetic resonance (NMR) spectroscopy has come a long way in
      characterizing the structure and function of biological molecules since the first
      one-dimensional spectrum of protein was recorded about 30 years ago. To date
      (September 1, 2012), there are 9,521 solution NMR structures in the Protein Data
      Bank, compared to 74,009 determined by crystallographic methods. Unlike X-ray and
      electron microscopy (EM) methods, which are based on the concepts of Fourier
      optics and image reconstruction, structure determination by NMR involves
      measuring structural restraints and finding structural solutions that satisfy the
      restraints. Although the NMR approach is much less direct in a physical sense, it
      has proven itself over the years to be capable of de novo structure determination
      at high precision. Moreover, the method is highly versatile and can be used in a
      variety of ways for addressing mechanistic questions. NMR measurements of protein
      internal dynamics and protein-protein or protein-ligand interaction are directly
      relevant to function in vivo because the molecules are often in physiological
      buffer conditions. The method can also be applied to investigate protein-folding
      intermediates, conformational changes, as well as intrinsically unfolded
      proteins. Recently, along with X-ray and EM, solution NMR has entered a state of
      rapid growth for structural studies of membrane proteins, already demonstrating
      its feasibility in de novo structure determination of membrane-embedded ion
      channels and receptors. As the hardware advances rapidly, especially in cryogenic
      probes that have much higher sensitivity, the sample concentration required for
      solution NMR investigation is decreasing, hopefully soon to a concentration level
      at which nonspecific protein aggregation is no longer an issue. After three
      decades of improvement in spectrometer technology, NMR pulse experiments, isotope
      labeling schemes, and structure determination software, we believe that solution
      NMR will truly enter the production phase in the next decade to answer biological
      questions of high impact, and to become more versatile than ever in complementing
      X-ray and EM in investigating protein structure and function.

PMID- 23132078
TI  - Structure-function insights of membrane and soluble proteins revealed by electron
      crystallography.
AB  - Electron crystallography is emerging as an important method in solving protein
      structures. While it has found extensive applications in the understanding of
      membrane protein structure and function at a wide range of resolutions, from
      revealing oligomeric arrangements to atomic models, electron crystallography has
      also provided invaluable information on the soluble alpha/beta-tubulin which
      could not be obtained by any other method to date. Examples of critical insights
      from selected structures of membrane proteins as well as alpha/beta-tubulin are
      described here, demonstrating the vast potential of electron crystallography that
      is first beginning to unfold.

PMID- 23132080
TI  - Processing of electron diffraction patterns with the XDP program.
AB  - Electron crystallography using two-dimensional crystals of membrane protein can
      provide high-resolution structure of a membrane protein within a lipid bilayer.
      With this technique, it is advantageous to use electron diffraction patterns to
      collect accurate intensities of the structure factors at high resolution. Here we
      describe how to process diffraction patterns using the XDP program and show what
      parameters are used and how they are determined in the process. Finally, the
      procedures for merging the intensity data will be described briefly.

PMID- 23132079
TI  - Lipid monolayer and sparse matrix screening for growing two-dimensional crystals
      for electron crystallography: methods and examples.
AB  - Electron microscopy provides an efficient method for rapidly assessing whether a
      solution of macromolecules is homogeneous and monodisperse. If the macromolecules
      can be induced to form two-dimensional crystals that are a single layer in
      thickness, then electron crystallography of frozen-hydrated crystals has the
      potential of achieving three-dimensional density maps at sub-nanometer or even
      atomic resolution. Here we describe the lipid monolayer and sparse matrix
      screening methods for growing two-dimensional crystals and present successful
      applications to soluble macromolecular complexes: carboxysome shell proteins and
      HIV CA, respectively. Since it is common to express recombinant proteins with
      poly-His tags for purification by metal affinity chromatography, the monolayer
      technique using bulk lipids doped with Ni(2+) lipids has the potential for broad
      application. Likewise, the sparse matrix method uses screening conditions for
      three-dimensional crystallization and is therefore of broad applicability.

PMID- 23132081
TI  - Future directions of electron crystallography.
AB  - In biological science, there are still many interesting and fundamental yet
      difficult questions, such as those in neuroscience, remaining to be answered.
      Structural and functional studies of membrane proteins, which are key molecules
      of signal transduction in neural and other cells, are essential for understanding
      the molecular mechanisms of many fundamental biological processes. Technological
      and instrumental advancements of electron microscopy have facilitated
      comprehension of structural studies of biological components, such as membrane
      proteins. While X-ray crystallography has been the main method of structure
      analysis of proteins including membrane proteins, electron crystallography is now
      an established technique to analyze structures of membrane proteins in the lipid
      bilayer, which is close to their natural biological environment. By utilizing
      cryo-electron microscopes with helium-cooled specimen stages, structures of
      membrane proteins were analyzed at a resolution better than 3 A. Such high
      resolution structural analysis of membrane proteins by electron crystallography
      opens up the new research field of structural physiology. Considering the fact
      that the structures of integral membrane proteins in their native membrane
      environment without artifacts from crystal contacts are critical in understanding
      their physiological functions, electron crystallography will continue to be an
      important technology for structural analysis. In this chapter, I will present
      several examples to highlight important advantages and to suggest future
      directions of this technique.

PMID- 23132082
TI  - Cyclohexane oxidation using Au/MgO: an investigation of the reaction mechanism.
AB  - The liquid phase oxidation of cyclohexane was undertaken using Au/MgO and the
      reaction mechanism was investigated by means of continuous wave (CW) EPR
      spectroscopy employing the spin trapping technique. Activity tests aimed to
      determine the conversion and selectivity of Au/MgO catalyst showed that Au was
      capable of selectivity control to cyclohexanol formation up to 70%, but this was
      accompanied by a limited enhancement in conversion when compared with the
      reaction in the absence of catalyst. In contrast, when radical initiators were
      used, in combination with Au/MgO, an activity comparable to that observed in
      industrial processes at ca. 5% conversion was found, with retained high
      selectivity. By studying the free radical autoxidation of cyclohexane and the
      cyclohexyl hydroperoxide decomposition in the presence of spin traps, we show
      that Au nanoparticles are capable of an enhanced generation of cyclohexyl alkoxy
      radicals, and the role of Au is identified as a promoter of the catalytic
      autoxidation processes, therefore demonstrating that the reaction proceeds via a
      radical chain mechanism.

PMID- 23132083
TI  - Evidence-based care: "this is the way we do it here".

PMID- 23132084
TI  - Intelligent infusion technologies: integration of a smart system to enhance
      patient care.
AB  - Medication errors, particularly intravenous therapy-related errors, still
      continue to occur, despite implementing newer technologies such as "smart pumps"
      to help avoid causing harm to patients. The Institute of Medicine report To Err
      Is Human, published in 1999, brought the problem of medication safety into the
      spotlight with a focus on improving the drug delivery systems of parenteral
      medications. The objective is to use this knowledge to help reduce errors,
      thereby promoting the best possible result for patients--no harm. Achieving this
      goal is not out of our reach, and with the execution of various point-of-care
      medication delivery systems, we are on the way to a safer practice.

PMID- 23132085
TI  - Decreasing central line infections and needlestick injury rates: combining best
      practice and introducing a luer-activated intravenous therapy system and
      antimicrobial intravenous connector.
AB  - The purpose of this study was to evaluate the impact of practice and intravenous
      (IV) therapy product changes on central line infections (CLIs) and needlestick
      injuries. Data were collected in 2009 and 2010 for 1 year before and after
      implementation of practice and product changes. Statistical significance was
      noted when comparing CLIs before and after implementation of an antimicrobial IV
      connector. The number of needlestick injuries also decreased by 12% during this
      time. Study results support ongoing clinical practice monitoring and education as
      well as the use of a luer-activated IV therapy system and an antimicrobial IV
      connector.

PMID- 23132086
TI  - Use of ketamine during procedural sedation: indications, controversies, and side
      effects.
AB  - Ketamine is a well-described anesthetic and analgesic, unique in its ability to
      preserve laryngeal reflexes and airway protection, and offered to a wide range of
      patients, although not necessarily widely used. Because it is considered an
      anesthetic, widespread use by all sedation providers is often limited despite its
      long history as a safe sedative. Because of its sympathomimetic effects, ketamine
      may be used in patients who are hypovolemic, including those who are experiencing
      traumatic or obstetric emergencies. The use of ketamine in patients with epilepsy
      or traumatic brain injury is more controversial. This article will explore the
      side effects of ketamine and current research that support or discourage its use
      in a variety of settings.

PMID- 23132087
TI  - Comparison of postinfusion phlebitis in intravenous push versus intravenous
      piggyback cefazolin.
AB  - Reducing health care costs without adversely affecting patient safety is a
      constant challenge for health care institutions. Cefazolin prophylaxis via
      intravenous push (IVP) is more cost-effective than via intravenous piggyback
      (IVPB). The purpose of this study was to determine whether patient safety would
      be compromised (ie, an increased rate of phlebitis) with a change to the IVP
      method. Rates of phlebitis in orthopedic surgical patients receiving cefazolin
      prophylaxis via IVP versus IVPB were evaluated in a prospective quasi
      experimental design of 240 patients. The first 120 subjects received cefazolin
      via IVPB, and the second 120 subjects received it via IVP. Results indicated no
      statistically significant difference in phlebitis rates in the IVPB (3.4%) versus
      the IVP groups (3.3%).

PMID- 23132088
TI  - Skin damage associated with intravenous therapy: common problems and strategies
      for prevention.
AB  - Infusion therapy is among the most common health care interventions, with
      approximately 90% of hospitalized patients receiving vascular access and an
      estimated 1.3 million home infusion therapies delivered annually. Whereas most
      individuals complete their therapy uneventfully, others experience alterations in
      skin integrity, some significant enough to disrupt therapy. There are limited
      published data on the incidence of skin damage associated with infusion therapy,
      and the etiology of damage has not been previously described in detail. Wound,
      ostomy, and continence (WOC) nurses have developed a significant understanding of
      skin-related problems and effective prevention strategies from over 40 years of
      experience with ostomy patients--another population in which adhesive wear is a
      constant and localized, superficial skin damage is common. This article will
      offer a WOC nursing perspective of skin damage and seek to provide a context for
      understanding and preventing skin damage in the infusion therapy patient.

PMID- 23132089
TI  - Accidental intravenous infusion of air: a concise review.
AB  - The unintended intravenous infusion of small volumes of air is common in clinical
      practice. International Electrotechnical Commission guidelines for infusion pumps
      permit infusion of up to 1 mL in 15 minutes and discount bubbles smaller than 50
      MUL. A review of the literature, however, suggests that these limits may be too
      generous. Neonates and patients with right-to-left cardiac shunts (eg, patent
      foramen ovale [PFO]) are at risk from lower volumes. Because PFO is prevalent in
      20% to 27% of healthy adults and generally asymptomatic, all patients are at risk
      from small air bubbles, although clinically significant air embolism from
      intravenous infusion is rare. Attention to good clinical practice and use of an
      inline air filter should be considered to reduce any risk.

PMID- 23132090
TI  - Evolution of the structural and electronic properties of beryllium-doped aluminum
      clusters: comparison with neutral and cationic aluminum clusters.
AB  - The lowest-energy structures of the Al(n)Be (n = 1-13) clusters are obtained and
      compared with the corresponding Al(n+1) and Al(n+1)(+) (n = 2-13) as well as
      Al(n)Mg clusters at the B3LYP/aug-cc-pVDZ level. The configurations of Al(n)Be
      show strong resemblances to those of pure Al(n+1) clusters, and the first three
      dimensional ground state in the Al(n)Be clusters occurs for Al(3)Be. Various
      properties of the Al(n)Be clusters are systematically investigated using the
      CCSD(T) method and their thermodynamic properties are also compared with those of
      corresponding Al(n+1)(+) clusters. The evolution of the energetic and electronic
      properties with the size of the clusters shows the unique stability of the 20
      valence electron systems Al(6)Be and Al(7)(+), which can be understood from the
      spherical jellium model (SJM). However, different from Al(7)(+) with
      1s(2)1p(6)1d(10)2s(2) shell occupation, the electronic-shell structure of
      1s(2)1p(6)1d(6)2s(2)1d(4) for the Al(6)Be cluster demonstrates that the impurity
      atom makes the molecular orbital distribution of doped clusters much more complex
      than that of pure metal clusters.

PMID- 23132091
TI  - Some forms of knowledge are more equal than others.

PMID- 23132093
TI  - Luer's lure: from an international standards perspective.

PMID- 23132092
TI  - Efficacy of high-dose nebulized colistin in ventilator-associated pneumonia
      caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii.
AB  - BACKGROUND: Colistin often remains the only active agent against multidrug
      resistant Gram-negative pathogens. The aim of the study was to assess efficacy of
      nebulized colistin for treating ventilator-associated pneumonia (VAP) caused by
      multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii. METHODS:
      One hundred and sixty-five patients with VAP caused by P. aeruginosa and A.
      baumannii were enrolled in a prospective, observational, and comparative study.
      The sensitive strain group included 122 patients with VAP caused by P. aeruginosa
      and A. baumannii susceptible to beta-lactams, aminoglycosides, or quinolones and
      treated with intravenous antibiotics for 14 days. The multidrug-resistant strain
      group included 43 patients with VAP caused by multidrug-resistant P. aeruginosa
      and A. baumannii and treated with nebulized colistin (5 million international
      units every 8 h) either in monotherapy (n=28) or combined to a 3-day intravenous
      aminoglycosides for 7-19 days. The primary endpoint was clinical cure rate.
      Aerosol was delivered using vibrating plate nebulizer. RESULTS: After treatment,
      clinical cure rate was 66% in sensitive strain group and 67% in multidrug
      resistant strain group (difference -1%, lower limit of 95% CI for difference 
      12.6%). Mortality was not different between groups (23 vs. 16%). Among 16
      patients with persisting or recurrent P. aeruginosa infection, colistin minimum
      inhibitory concentration increased in two patients. CONCLUSION: Nebulization of
      high-dose colistin was effective to treat VAP caused by multidrug-resistant P.
      aeruginosa or A. baumannii. Its therapeutic effect was noninferior to intravenous
      beta-lactams associated with aminoglycosides or quinolones for treating VAP
      caused by susceptible P. aeruginosa and A. baumannii.

PMID- 23132094
TI  - From chaos to split-ups--SHG microscopy reveals a specific remodelling mechanism
      in ageing dystrophic muscle.
AB  - Duchenne muscular dystrophy (DMD) is a common inherited muscle disease showing
      chronic inflammation and progressive muscle weakness. Absent dystrophin renders
      sarcolemma more Ca(2+) -permeable, disturbs signalling and triggers inflammation.
      Sustained degeneration/regeneration cycles render muscle cytoarchitecture
      susceptible to remodelling. Quantitative morphometry was introduced in living
      cells using second-harmonic generation (SHG) microscopy of myosin. As the time
      course of cellular remodelling is not known, we used SHG microscopy in mdx muscle
      fibres over a wide age range for three-dimensional (3D) rendering and detection
      of verniers and cosine angle sums (CASs). Wild-type (wt) and transgenic mini
      dystrophin mice (MinD) were also studied. Vernier densities (VDs) declined in wt
      and MinD fibres until adulthood, while in mdx fibres, VDs remained significantly
      elevated during the life span. CAS values were close to unity in adult wt and
      MinD fibres, in agreement with tight regular myofibril orientation, while always
      smaller in mdx fibres. Using SHG 3D morphometry, we identified two types of
      altered ultrastructure: branched fibres and a novel, previously undetected
      'chaotic' fibre type, both of which can be classified by distinct CAS and VD
      combinations. We present a novel model of tissue remodelling in dystrophic
      progression with age that involves the transition from normal to chaotic to
      branched fibres. Our model predicts a ~50% contribution of altered
      cytoarchitecture to progressive force loss with age. We also provide an improved
      automated image algorithm that is suitable for future ageing studies in human
      myopathies.

PMID- 23132095
TI  - Sonographic evaluation of vascular pulmonary reactivity following oxygen
      administration in fetuses with normal lung development.
AB  - OBJECTIVE: This study aimed to establish nomograms for sonographic assessment of
      fetal pulmonary vascular reactivity following maternal hyperoxygenation. STUDY
      DESIGN: Sixty-two healthy fetuses were assessed at four weekly intervals from 26
      weeks onwards. Pulmonary reactivity was evaluated using Doppler ultrasound in the
      main pulmonary artery and in the first branch of this main pulmonary artery. The
      difference in pulsatility index (?PI) during maternal inhalation of a mixture of
      room air and oxygen (9 L/min) for at least 10 min was expressed as a percentage.
      Nomograms were constructed, and Kaplan-Meier curves were used to express the
      occurrence of a reactive test (?PI >= 20%) with advancing gestation. RESULTS: In
      the first branch, linear regression analysis revealed a significant correlation
      of ?PI (%) with gestational age (r(2) = 0.04, p = 0.0057). Large inter-individual
      and intra-individual variability was noted. The ?PI (%) in the main pulmonary
      artery remained constant throughout gestation (6.62 +/- 17.83%). CONCLUSION:
      Vascular reactivity in the pulmonary circulation increases in the first branch of
      the pulmonary artery. Large individual variability is limiting its use as a
      management tool.

PMID- 23132100
TI  - With one voice: continuing the conversation with New Jersey physicians.

PMID- 23132097
TI  - Effects of premature termination codon polymorphisms in the Drosophila
      pseudoobscura subclade.
AB  - Premature termination codon (PTC) mutations can have dramatic effects--both
      adaptive and deleterious--on gene expression and function. Here, we examine the
      number and selective effects of PTC mutations within the Drosophila pseudoobscura
      subclade using 18 resequenced genomes aligned to the reference genome. We located
      and characterized 1,679 PTC mutations in 605 genes across each of these genomes
      relative to the D. pseudoobscura reference genome, and use RT-PCR to confirm
      transcription of a subset of these genes containing PTC mutations. We confirm
      previous findings that genes containing PTC mutations are less selectively
      constrained and less broadly expressed than non-PTC-containing genes, suggesting
      that the most of these mutations are at least mildly deleterious. Further, we
      find highly significant codon usage bias in regions downstream of the PTC in 38
      of these PTC-containing genes, suggesting that some of these PTC mutations--if
      not alternatively spliced out of the transcript--have neutral effects.
      Ultimately, these analyzes support the view that the PTC mutations are mostly
      detrimental, but are nonetheless common enough in genomes that a subset could be
      effectively neutral.

PMID- 23132099
TI  - Novel phospholyl(diphenylphosphino)methane-ruthenium complexes: unexpected non
      assisted cis to trans isomerization of [RuCl2(kappa(2)-P-P')2].
AB  - Using the unsymmetrical P-P' phospholyl(phosphino)methane ligand, complex cis
      [RuCl(2)(kappa(2)-P-P')(2)] is easily prepared from [RuCl(2)(DMSO)(4)]. The two
      phosphole-phosphorus atoms lie in the trans position to the two cis-chloro
      ligands. This complex slowly isomerizes spontaneously at 20  degrees C to the
      trans-[RuCl(2)(kappa(2)-P-P')(2)] diastereoisomer where the two phosphole
      moieties are mutually trans, as well as the two chloro ligands and the two Ph(2)P
      moieties. DFT calculations show that this non-classical cis-trans isomerisation
      process requires a 3 kcal mol(-1) energy and involves the decoordination of a
      phosphole arm.

PMID- 23132101
TI  - Point of view: the Supreme Court did not stop Obamacare but congress must.

PMID- 23132102
TI  - Addressing vaccine hesitancy.

PMID- 23132103
TI  - Accountable care organizations: industry experts report on New Jersey's progress.

PMID- 23132096
TI  - Membrane trafficking in neuronal maintenance and degeneration.
AB  - Defects in membrane trafficking and degradation are hallmarks of most, and maybe
      all, neurodegenerative disorders. Such defects typically result in the
      accumulation of undegraded proteins due to aberrant endosomal sorting, lysosomal
      degradation, or autophagy. The genetic or environmental cause of a specific
      disease may directly affect these membrane trafficking processes. Alternatively,
      changes in intracellular sorting and degradation can occur as cellular responses
      of degenerating neurons to unrelated primary defects such as insoluble protein
      aggregates or other neurotoxic insults. Importantly, altered membrane trafficking
      may contribute to the pathogenesis or indeed protect the neuron. The observation
      of dramatic changes to membrane trafficking thus comes with the challenging need
      to distinguish pathological from protective alterations. Here, we will review our
      current knowledge about the protective and destructive roles of membrane
      trafficking in neuronal maintenance and degeneration. In particular, we will
      first focus on the question of what type of membrane trafficking keeps healthy
      neurons alive in the first place. Next, we will discuss what alterations of
      membrane trafficking are known to occur in Alzheimer's disease and other
      tauopathies, Parkinson's disease, polyQ diseases, peripheral neuropathies, and
      lysosomal storage disorders. Combining the maintenance and degeneration
      viewpoints may yield insight into how to distinguish when membrane trafficking
      functions protectively or contributes to degeneration. 

PMID- 23132104
TI  - A historian's look at the 2012 IOM report on the future of nursing.

PMID- 23132105
TI  - Ethical obligations under New Jersey's mandated pharmaceutical disclosures.

PMID- 23132106
TI  - Informed consent and confidentiality for New Jersey minors.

PMID- 23132107
TI  - Physician assistants: liability and regulatory issues.

PMID- 23132108
TI  - Travel-related health risks part 2: emerging mosquito-borne infectious illnesses.

PMID- 23132109
TI  - James Still: "the Black Doctor of the Pines".

PMID- 23132110
TI  - Fine control of nanoparticle sizes and size distributions: temperature and ligand
      effects on the digestive ripening process.
AB  - It is demonstrated that a fine control over the size and size distribution of
      nanoparticles could be achieved using digestive ripening at different
      temperatures. Such variations in size and size distributions hugely influence the
      self-assembled processes in nanoparticles, and result in superlattice structures
      that are controlled by subtle interplay between ligand orientational entropy and
      their interdigitation and the van der Waals attraction between the metal cores.

PMID- 23132112
TI  - Gene patents do not hinder academic research.

PMID- 23132113
TI  - rapidSTORM: accurate, fast open-source software for localization microscopy.

PMID- 23132114
TI  - ORCAE: online resource for community annotation of eukaryotes.

PMID- 23132115
TI  - Genome-editing tools storm ahead.

PMID- 23132116
TI  - Modular gene-circuit design takes two steps forward.

PMID- 23132117
TI  - Spinning up mass spectrometry for whole protein complexes.

PMID- 23132118
TI  - A travel guide to Cytoscape plugins.
AB  - Cytoscape is open-source software for integration, visualization and analysis of
      biological networks. It can be extended through Cytoscape plugins, enabling a
      broad community of scientists to contribute useful features. This growth has
      occurred organically through the independent efforts of diverse authors, yielding
      a powerful but heterogeneous set of tools. We present a travel guide to the world
      of plugins, covering the 152 publicly available plugins for Cytoscape 2.5-2.8. We
      also describe ongoing efforts to distribute, organize and maintain the quality of
      the collection.

PMID- 23132120
TI  - Pulmonary embolism secondary to balloon-occluded retrograde transvenous
      obliteration for gastric varix.

PMID- 23132119
TI  - Environmental risk factors and perinatal outcomes in preterm newborns, according
      to family recurrence of prematurity.
AB  - OBJECTIVE: We analyzed the role of environmental risk factors, sociodemographic
      characteristics, clinical characteristics, and reproductive history in preterm
      births and their associated perinatal outcomes in families classified according
      to their histories of preterm recurrence among siblings. STUDY DESIGN: A
      retrospective study was conducted at Nuestra Senora de la Merced Maternity
      Hospital in the city of Tucuman, Argentina. A total of 348 preterm, non
      malformed, singleton children born to multipara women were reviewed. The family
      history score described by Khoury was applied, and families were classified as
      having no, medium, or high genetic aggregation. RESULTS: Families with no
      familial aggregation showed a higher rate of short length of cohabitation,
      maternal urinary tract infections during the current pregnancy, and maternal
      history of miscarriage during the previous pregnancy. Families with a high level
      of aggregation had a significantly higher incidence of pregnancy complications,
      such as diabetes, hypertension, and immunologic disorders. CONCLUSION:
      Reproductive histories clearly differed between the groups, suggesting both a
      different response to environmental challenges based on genetic susceptibility
      and the activation of different pathophysiological pathways to determine the
      duration of pregnancy in each woman.

PMID- 23132121
TI  - Secondary sentinel node biopsy after previous excision of the primary tumor in
      squamous cell carcinoma of the vulva.
AB  - BACKGROUND: To reduce morbidity of radical groin dissection, the sentinel-node
      (SLN) procedure was implemented for the treatment of vulvar cancer. It has been
      proven to be a safe alternative in early-stage disease. Feasibility and safety of
      the procedure after previous vulvar surgery remain unclear. METHODS: A total of
      106 patients with primary vulvar cancer undergoing the SLN procedure were
      analyzed. Seventy-four patients received the SLN procedure concomitant to vulvar
      surgery [primary-sentinel group (PSG)], whereas 32 patients had vulvar surgery
      before secondary SLN [secondary-sentinel group (SSG)]. RESULTS: SLN detection was
      possible in all patients. Three (9.4 %) patients in the SSG and 30 (40.5 %) in
      the PSG had metastatic spread to the SLN and underwent radical groin dissection.
      Median interval between vulva surgery and secondary sentinel was 34 days (range,
      7-98). In the SSG tumor, stages were earlier with smaller tumor size (median 19
      mm in the PSG vs. 9 mm in the SSG) and lesser invasion depth (4 vs. 2 mm; p <
      0.001). There were no groin recurrences in the SSG and 5.4 % in the PSG. No
      significant difference regarding disease-free survival (DFS) could be detected (3
      year DFS of 72.5 % in the PSG compared with 92.5 % in the SSG (median DFS not
      reached, p = 0.114)). Adjusting for potential confounders (tumor stage, nodal
      status, tumor size, invasion depth) did not alter the results with regards to
      DFS. CONCLUSIONS: Our results suggest that a secondary SLN procedure after
      previous vulvar surgery is feasible and can accurately reflect the groin status
      of selected patients. Ideally, prospective trials should be conducted to verify
      accuracy and oncologic safety of the procedure.

PMID- 23132123
TI  - Classifying highly imbalanced ICU data.
AB  - Highly imbalanced data sets are those where the class of interest is rare. In
      this paper, we compare the performance of several common data mining methods,
      logistic regression, discriminant analysis, Classification and Regression Tree
      (CART) models, C5, and Support Vector Machines (SVM) in predicting the discharge
      status (alive or deceased, with "deceased" being the class of interest) of
      patients from an Intensive Care Unit (ICU). Using a variety of misclassification
      cost ratio (MCR) values and using specificity, recall, precision, the F-measure,
      and confusion entropy (CEN) as criteria for evaluating each method's performance,
      C5 and SVM performed better than the other methods. At a MCR of 100, C5 had the
      highest recall and SVM the highest specificity and lowest CEN. We also used
      Hand's measure to compare the five methods. According to Hand's measure, logistic
      regression performed the best. This article makes several contributions. We show
      how the use of MCR for analyzing imbalanced medical data significantly improves
      the method's classification performance. We also found that the F-measure and
      precision did not improve as the MCR was increased.

PMID- 23132124
TI  - Is pentoxifylline plus vitamin E an effective treatment for radiation-induced
      optic neuropathy?

PMID- 23132125
TI  - Predictors of initial levels and trajectories of depressive symptoms in women
      with breast cancer undergoing radiation therapy.
AB  - BACKGROUND: Women with breast cancer undergoing radiation therapy (RT) are at
      increased risk for depressive symptoms. However, only 4 studies specifically
      evaluated changes in and predictors of depressive symptoms in these patients.
      OBJECTIVE: This study evaluated changes in depressive symptoms from the
      initiation of and through 6 months following RT and investigated whether specific
      demographic, clinical, symptom, and psychological adjustment characteristics
      predicted initial levels and trajectories of depressive symptoms. METHODS: A
      total of 184 women with breast cancer completed the Center for Epidemiologic
      Studies-Depression Scale that evaluated depressive symptoms prior to and
      approximately 1, 2, 3, and 6 months after the initiation of RT. Hierarchical
      linear modeling was used for these analyses. RESULTS: Approximately one-fourth of
      patients had clinically meaningful levels of depressive symptoms prior to RT, but
      the trajectory of depressive symptoms improved over time. Women with less
      education, children living at home, a higher level of sleep disturbance, worry
      about disease outcome, less meaning in life, and less support from family and
      friends had higher levels of depressive symptoms prior to RT. CONCLUSIONS: Some
      women with breast cancer experience depressive symptoms prior to, during, and
      after RT, and specific demographic, clinical, symptom, and psychological
      adjustment characteristics identified women at higher risk for depressive
      symptoms. IMPLICATIONS FOR PRACTICE: Nurses could use knowledge of the predictors
      to identify patients at risk for depressive symptoms and to educate patients
      about how depressive symptoms may change during and following RT for breast
      cancer.

PMID- 23132126
TI  - A labor of love: the influence of cancer caregiving on health behaviors.
AB  - BACKGROUND: Evidence suggests that emotional distress and objective demands of
      cancer caregiving are comparable to those of dementia caregiving, yet little
      research has focused on the physical health of cancer caregivers. Whether the
      stress leads directly to changes in health or whether the stress leads to changes
      in health behaviors, which in turn affect health, has not been systematically
      examined. OBJECTIVE: The objective of this study was to review the research
      literature regarding changes in health behaviors associated with caring for an
      individual with cancer. METHODS: Literature was reviewed from multiple databases
      including CINAHL (Cumulative Index to Nursing and Allied Health Literature),
      CINAHL Plus, PsycNET, PubMed, SCOPUS, EMBASE, and Web of Science. Key words
      included "health behavior," "health promotion," "caregivers/caregiving,"
      "cancer/oncology," "diet/nutrition," "exercise/physical activity," "stress
      management," "smoking" and "alcohol." Studies were included if they involved
      informal adult caregivers and at least 1 behavior associated with a healthy
      lifestyle. Of the 866 studies identified, 8 met the criteria. RESULTS: Studies
      revealed conflicting information, with some suggesting deleterious changes in
      behaviors, whereas others found the changes protective. CONCLUSIONS: The lack of
      uniformity of terminology and conflicting findings make it difficult to conclude
      the impact of the caregiving experience on the health behaviors of cancer
      caregivers. Something is placing caregivers at risk for illness and early death,
      but the mechanisms behind the risk and the role of unhealthy behaviors are not
      clear. IMPLICATIONS FOR PRACTICE: At a minimum, cancer caregivers should be
      screened for behavior changes and disease risk. Developing standardized measures
      for future research including controlled, longitudinal studies is needed.

PMID- 23132128
TI  - Education and training of public health professionals in the European Region:
      variation and convergence.
AB  - OBJECTIVES: To assess the exit competences of public health graduates across a
      diverse European landscape. METHODS: The target population comprised 80 full
      institutional members of the Association of Schools of Public Health in the
      European Region with a participation rate 82.5 %. The web-based questionnaire
      covered institutional profiles and the ranking of exit competences for master of
      public health programmes, grouped according to WHO Essential Public Health
      Operations. RESULTS: European schools and departments usually are small units,
      funded from tax money. A total of 130 programmes have been indicated, together
      releasing 3,035 graduates in the last year before the survey. All competence
      groups showed high reliability and high internal consistency (alpha > 0.75, p <
      0.01). The best teaching output has been assessed for health promotion, followed
      by disease prevention and identification of health hazards in the community, the
      least in emergency preparedness. CONCLUSIONS: Given the fragmentation of the
      institutional infrastructure, the harmonisation of programme content and thinking
      is impressive. However, the educational capacity in the European Region is far
      from being sufficient if compared to aspired US levels.

PMID- 23132127
TI  - Treatment for adult idiopathic and Wegener-associated subglottic stenosis.
AB  - The aim of the study is to present the results of combination treatment for adult
      non-traumatic subglottic stenosis (SGS). This is a retrospective chart review of
      12 female patients (age range 32-76 years) with idiopathic SGS (eight patients)
      and Wegener's granulomatosis. All patients had a hard and 11 a short (less than 1
      cm) stenosis. Eleven patients were treated with endoscopic CO(2) laser, one with
      Nd-YAG laser. Topical triamcinolone was applied to all. In 10 patients, topical
      mitomycin C (MMC) was additionally applied. Symptom severity and airway
      resistance (AR) were evaluated pre- and post-interventionally. Postoperatively,
      oral steroids (and/or methotrexate) and proton pump inhibitors (PPI) were
      prescribed. Follow-up period ranged between 7 and 115 months. All patients
      reported a significant improvement in obstructive symptoms. Average AR
      preoperatively was 1.004 kPa/(L/s) and postoperatively 0.526 kPa/(L/s). Three
      patients underwent surgery once, 2 required a second surgery, 5 were operated 3
      times, one 5 times, and one 7 times. The latter two patients had not received
      local MMC treatment. Endoscopic laser surgery combined with local MMC and
      triamcinolone application and postoperative oral steroid/methotrexate and PPI
      therapy provides a treatment option that results in prolongation of the symptom
      free time intervals and avoidance of open surgery in patients with idiopathic and
      Wegener-associated hard and short SGS.

PMID- 23132129
TI  - Controlled evaporative self-assembly of poly(3-hexylthiophene) monitored with
      confocal polarized Raman spectroscopy.
AB  - Highly-ordered, parallel gradient P3HT stripes are fabricated through a facile
      deposition method based on controlled evaporative self-assembly (CESA). Confocal
      polarized Raman spectroscopy is employed to determine the orientation of P3HT
      chains in individual stripes and spacing. This is the first report on orientation
      at the molecular level, beyond sole morphology, in the patterns assembled by
      CESA. P3HT chains tend to aggregate into one-dimensional nanowhiskers in solution
      upon aging, leading to a time-evolved dispersion composed of isolated chains and
      nanowhiskers. A corresponding evolution of morphology and molecular orientation
      in the obtained patterns is observed when assembling P3HT solutions with
      different aging times. The stripes evolve gradually from slim stripes with
      fingering instabilities for fresh solution into highly regular, perfect stripes
      for sufficiently aged solution. In the stripe region, P3HT backbone chains align
      parallel to the contact line for fresh solution whereas perpendicular for aged
      solution. The thermodynamic multicomponent system gives greater variety to the
      CESA study.

PMID- 23132130
TI  - When health care workers experience mental ill health: institutional practices of
      silence.
AB  - Based on findings from an institutional ethnography in a large mental health
      organization, we explore how institutional forces shape the experiences of health
      care workers with mental health issues. We interviewed 20 employees about their
      personal experiences with mental health issues and work and 12 workplace
      stakeholders about their interactions with workers who had mental health issues.
      We also reviewed organizational texts related to health, illness, and
      productivity. In analyzing transcripts and texts, silence emerged as a core
      underlying process characterizing individual and organizational responses to
      employees with mental health issues. Silence was an active practice that took
      many forms; it was pervasive, complex, and at times, paradoxical. It served many
      functions for workers and the organization. We discuss the theoretical and
      practical implications of the findings for workers with mental health issues.

PMID- 23132131
TI  - Sandwich-type tetrakis(phthalocyaninato) rare earth(III)-cadmium(II) quadruple
      deckers. The effect of f-electrons.
AB  - Systematic studies over the synthesis of sandwich-type
      tetrakis[2,3,9,10,16,17,23,24-octa(octyloxy)phthalocyaninato] heterometallic
      complexes for the whole series of lanthanide metals and yttrium have been
      conducted, revealing the dependence of the formation and isolation of the target
      quadruple-decker compounds on the rare earth ionic size, which is supported by
      the electronic absorption spectroscopic result. Nevertheless, comparative
      electrochemical investigations between the lanthanide and yttrium quadruple
      deckers reveal the effect of f-electrons, actually the f-f interaction between
      the lanthanide centers separated by a divalent cadmium ion in the
      tetrakis(phthalocyaninato) lanthanide-cadmium complexes. The effective imaginary
      third order molecular hyperpolarizability (Im{chi((3))}) of the whole series of
      complexes in the range of 2.04-2.41 * 10(-11) esu is, however, not ionic size
      dependent.

PMID- 23132132
TI  - Ultrasound measurements of live and carcass traits in Tswana goat kids raised
      under semi-intensive system in South-eastern Botswana.
AB  - The aim of this study was to characterise ultrasound measurements of live and
      carcass traits in intact males, females and castrated Tswana goat kids from birth
      to 12 months of age raised under semi-intensive system in South-eastern Botswana.
      Measurements were recorded in 15 castrates, 15 intact males and 15 female Tswana
      goat kids randomly selected at birth. Ultrasonic fat and muscle depths were
      measured at the first, third/fourth, sixth/seventh, ninth/tenth and 12th/13th
      thoracic; first, third and fifth lumbar and first, second/third and fourth/fifth
      sternal vertebrae, fortnightly for the first 6 months and then monthly for the
      remaining 6 months. The animals were stunned and humanely slaughtered at 12
      months of age, and ultrasound and shatterproof ruler were used to measure fat and
      muscle depths on the carcasses at similar sites as on live animals. A real-time B
      mode ultrasound scanner fitted with LV2-1 probe operating at 7.5 MHz (Explorer V5
      Vet Laptop B-Ultrasonic Scanner UMC Technology Development Co., Ltd, China) was
      used to predict ultrasound measurements on live animals and their carcasses. Data
      were analysed using general linear model in statistical analysis system. Muscle
      depth measurements increased significantly (p < 0.05) with age in all sites of
      measurements. However, there was no significant difference between the sexes at
      different sites of muscle depth measurements at the same age. Muscle depth at the
      sternal vertebrae was significantly deeper (almost 55 mm at 12 months of age)
      than 16 mm at thoracic and 16 mm at lumbar vertebrae at 12 and 8 months of age,
      respectively. No subcutaneous fat depth measurements were recorded in the lumbar
      vertebrae (0.00 +/- 0.00) and the thoracic (0.00 +/- 0.00) regions in all sex
      groups. However, fourth and fifth sternal vertebrae showed considerably deeper
      amount of subcutaneous fat suitable for taking fat measurements as age increases
      (2.07 +/- 0.23 mm females, 1.50 +/- 0.43 mm intact males and 1.80 +/- 0.38 mm
      castrates) at 12 months of age. All correlations between live and carcass
      ultrasound measurements and also between ultrasound carcass and ruler
      measurements were very high (r (2) = 0.96 to 1.00) for all the sexes indicating
      that live ultrasound measurements are suitable for use in this meat breed. More
      research is needed to evaluate the relationships between live ultrasonic
      measurements and carcass yield in the different sexes of Tswana goat kids.

PMID- 23132133
TI  - Molecular genotyping of Mycobacterium bovis isolated from cattle tissues in the
      North West Region of Cameroon.
AB  - An epidemiological study was carried out to determine the Mycobacterium bovis
      strains causing bovine tuberculosis (TB) in cattle in North West Cameroon.
      Suspected TB lesions from slaughtered cattle were cultured on Lowenstein-Jensen
      and Middlebrook 7 H9 media to isolate mycobacteria agents for molecular
      genotyping using deletion analysis and spoligotyping. PCR-based genomic deletion
      typing showed that 54 of 103 tubercle bacilli isolated from cattle tissue were M.
      bovis strains and the African 1 clonal complex was widespread in affected cattle.
      Spoligotyping analysis revealed a closely related group of five M. bovis strains.
      SB0953, the dominant spoligotype pattern, and four new patterns identified as
      SB2161, SB2162, SB2663 and SB2664 according to the www.Mbovis.org international
      spoligotype database were identified. These spoligotypes were similar to other M.
      bovis strains recovered from bordering regions and other parts of Africa. The
      findings provided useful facts on the zoonotic risks of bovine TB and
      overwhelming evidence of the significance of M. bovis infection to human TB in
      the North West Region of Cameroon. The study revealed that bovine TB was
      widespread in cattle destined for human consumption and also has important
      implications for the control of TB in animals and humans in Cameroon.

PMID- 23132134
TI  - The effect of a catastrophic flood disaster on livestock farming in Nakhon Sawan
      province, Thailand.
AB  - In 2011, a catastrophic flood disaster in Thailand affected not only humans but
      also took animal lives. Data on livestock losses, including death, loss, and
      decreased production, were collected in Nakhon Sawan province. The time-series
      map of the flooded area from August to December 2011 was available online from
      the Geo-informatics and Space Technology Development Agency. To evaluate the high
      density areas of livestock loss, a spatial hot spot analysis was performed. The
      Getis-Ord Gi statistic with weighted zone of indifference and the Euclidean
      distance measurement were employed to identify spatial clusters of species that
      were affected by the flood. The results indicated that the majority of livestock
      losses were from poultry and swine farms. The density of poultry and swine loss
      was significantly different between sub-districts with clusters of high-density
      loss alongside the river, particularly in Chum Saeng and Kao Liew. Using spatial
      hot spot analysis as a tool to classify and rank the areas with high flood risks
      provides an informative outline for farmers to be aware of potential flood
      damage. To avoid unexpected loss from flooding, poultry and swine farms in risk
      areas should be properly managed, particularly during the flooding season between
      August and December.

PMID- 23132135
TI  - Prevalence and risk factors associated with Cryptosporidium spp. infection in
      young domestic livestock in India.
AB  - A total of 938 faecal samples (461 cattle calves, 264 buffalo calves, 55 lambs,
      116 kids and 42 piglets) from different livestock farms and individual small
      holdings in six targeted states of India were collected and screened by modified
      Ziehl-Neelsen staining technique to determine the prevalence of Cryptosporidium
      spp. and its association with age, sex, season and faecal consistency in
      domesticated animals. Overall, 16.2 % of the animals were positive for
      Cryptosporidium infection with prevalence of 16.3, 24.2, 1.8, 3.5 and 19.1 % in
      cattle calves, buffalo calves, lambs, kids and piglets, respectively. The
      prevalence of infection was significantly higher (p<0.05) in bovines (19.3 %
      cattle and 33.7 % buffalo) below 1 month of age than in animals between 1 and 3
      months of age. But in piglets, it was higher in the age group of 1 to 3 months
      (22.6 %) than in younger animals (9.1 %). Also, higher prevalence (p>0.05) was
      recorded in females than in males. Seasons had a significant effect (p<0.05) on
      the prevalence of infection in large ruminants, with the highest prevalence in
      monsoon (cattle 28.8 % and buffalo 36.6 %) followed by pre-monsoon and post
      monsoon season. However, in case of sheep and goats, the prevalence was higher
      (p>0.05) in post-monsoon than in monsoon season. A high degree of association was
      noticed between Cryptosporidium infection and diarrhoea in ruminants screened
      during the present study. But, in case of pigs, the prevalence was higher in non
      diarrhoeic than in diarrhoeic animals. Genotyping of Cryptosporidium spp. based
      on nested PCR amplification of partial 18S rRNA and its subsequent digestion with
      SspI, VspI and MboII restriction enzymes revealed prevalence of Cryptosporidium
      parvum in representative number of positive samples of cattle, buffalo and goats.

PMID- 23132136
TI  - Substituted N-benzylpyrazine-2-carboxamides: synthesis and biological evaluation.
AB  - A series of twelve amides was synthesized via aminolysis of substituted
      pyrazinecarboxylic acid chlorides with substituted benzylamines. Compounds were
      characterized with analytical data and assayed in vitro for their
      antimycobacterial, antifungal, antibacterial and photosynthesis-inhibiting
      activity. 5-tert-Butyl-6-chloro-N-(4-methoxybenzyl)pyrazine-2-carboxamide (12)
      has shown the highest antimycobacterial activity against Mycobacterium
      tuberculosis (MIC = 6.25 &#181;g/mL), as well as against other mycobacterial
      strains. The highest antifungal activity against Trichophyton mentagrophytes, the
      most susceptible fungal strain tested, was found for 5-chloro-N-(3
      trifluoromethylbenzyl)-pyrazine-2-carboxamide (2, MIC = 15.62 &#181;mol/L). None
      of the studied compounds exhibited any activity against the tested bacterial
      strains. Except for 5-tert-butyl-6-chloro-N-benzylpyrazine-2-carboxamide (9,
      IC(50) = 7.4 &#181;mol/L) and 5-tert-butyl-6-chloro-N-(4-chlorobenzyl)pyrazine-2
      carboxamide (11, IC(50) = 13.4 &#181;mol/L), only moderate or weak photosynthesis
      inhibiting activity in spinach chloroplasts (Spinacia oleracea L.) was detected.

PMID- 23132137
TI  - Fabrication of mesoporous silica shells on solid silica spheres using anionic
      surfactants and their potential application in controlling drug release.
AB  - In this work, mesoporous shells were constructed on solid silica cores by
      employing anionic surfactante. A co-structure directing agent (CSDA) has assisted
      the electrostatic interaction between negatively charged silica particles and the
      negatively charged surfactant molecules. Synthetic parameters such as reaction
      time and temperature had a significant impact on the formation of mesoporous
      silica shelld and their textural properties such as surface area and pore volume.
      Core-mesoporous shell silica spheres were characterized by small angle X-ray
      scattering, transmission electron microscopy, and N(2)
      adsorption&#8211;desorption analysis. The synthesized particles have a uniformly
      mesoporous shell of 34&#8211;65 nm and possess a surface area of ca. 7&#8211;324
      m2/g, and pore volume of ca. 0.008&#8211;0.261 cc/g. The core-mesoporous shell
      silica spheres were loaded with ketoprofen drug molecules. The in vitro drug
      release study suggested that core-mesoporous shell silica spheres are a suitable
      nanocarrier for drug molecules offering the possibility of having control over
      their release rate.

PMID- 23132138
TI  - Coupling two different nucleic acid circuits in an enzyme-free amplifier.
AB  - DNA circuits have proven to be useful amplifiers for diagnostic applications, in
      part because of their modularity and programmability. In order to determine
      whether different circuits could be modularly stacked, we used a catalytic
      hairpin assembly (CHA) circuit to initiate a hybridization chain reaction (HCR)
      circuit. In response to an input nucleic acid sequence, the CHA reaction
      accumulates immobilized duplexes and HCR elongates these duplexes. With
      fluorescein as a reporter each of these processes yielded  10-fold signal
      amplification in a convenient 96-well format. The modular circuit connections
      also allowed the output reporter to be readily modified to a G-quadruplex-DNAzyme
      that yielded a fluorescent signal.

PMID- 23132139
TI  - Preparation of candesartan and atorvastatin nanoparticles by solvent evaporation.
AB  - The solubility, absorption and distribution of a drug are involved in the basic
      aspects of oral bioavailability Solubility is an essential characteristic and
      influences the efficiency of the drug. Over the last ten years, the number of
      poorly soluble drugs has steadily increased. One of the progressive ways for
      increasing oral bioavaibility is the technique of nanoparticle preparation, which
      allows many drugs to thus reach the intended site of action. Candesartan
      cilexetil and atorvastatin, belonging to class II of the biopharmaceutical
      classification system, were chosen as model active pharmaceutical ingredients in
      this study. Forty samples were prepared either by antisolvent
      precipitation/solvent evaporation method or by the emulsion/solvent evaporation
      technique with various commonly used surface-active excipients as nanoparticle
      stabilizers. All samples were analyzed by means of dynamic light scattering. The
      particle size of the determined 36 nanoparticle samples was to 574 nm, whereas 32
      samples contained nanoparticles of less than 200 nm. Relationships between
      solvents and excipients used and their amount are discussed. Based on the results
      the investigated solvent evaporation methods can be used as an effective and an
      affordable technique for the preparation  of nanoparticles.

PMID- 23132141
TI  - Screened-exchange density functionals with broad accuracy for chemistry and solid
      state physics.
AB  - We present two new exchange-correlation functionals for hybrid Kohn-Sham
      electronic structure calculations based on the nonseparable functional form
      introduced recently in the N12 and MN12-L functionals but now with the addition
      of screened Hartree-Fock exchange. The first functional depends on the density
      and the density gradient and is called N12-SX; the second functional depends on
      the density, the density gradient, and the kinetic energy density and is called
      MN12-SX. Both new functionals include a portion of the Hartree-Fock exchange at
      short-range, but Hartree-Fock exchange is screened at long range. The accuracies
      of the two new functionals are compared to those of the recent N12 and MN12-L
      local functionals to show the effect of adding screened exchange, are compared to
      the previously best available screened exchange functional, HSE06, and are
      compared to the best available global-hybrid generalized gradient approximation
      (GGA) and to a high-performance long-range-corrected meta-GGA.

PMID- 23132140
TI  - Azide-alkyne Huisgen [3+2] cycloaddition using CuO nanoparticles.
AB  - Recent developments in the synthesis of CuO nanoparticles (NPs) and their
      application to the [3+2] cycloaddition of azides with terminal alkynes are
      reviewed. With respect to the importance of click chemistry, CuO hollow NPs, CuO
      hollow NPs on acetylene black, water-soluble double-hydrophilic block copolymer
      (DHBC) nanoreactors and ZnO&#8211;CuO hybrid NPs were synthesized. Non
      conventional energy sources such as microwaves and ultrasound were also applied
      to these click reactions, and good catalytic activity with high regioselectivity
      was observed. CuO hollow NPs on acetylene black can be recycled nine times
      without any loss of activity, and water-soluble DHBC nanoreactors have been
      developed for an environmentally friendly process.

PMID- 23132142
TI  - Structure-function analysis of Arabidopsis thaliana histidine kinase AHK5 bound
      to its cognate phosphotransfer protein AHP1.
AB  - The multi-step phosphorelay (MSP) system defines a key signal transduction
      pathway in plants and many eukaryotes. In this system, external stimuli first
      lead to the activation of a histidine kinase, followed by transfer of a
      phosphoryl group from the receiver domain of the kinase (HK(RD)) to downstream,
      cytosolic phosphotransfer proteins (HPs). In order to establish the determinants
      of specificity for this signaling relay system, we have solved the first crystal
      structure of a plant HK(RD), AHK5(RD), in complex with one of its cognate HPs,
      AHP1. AHP1 binds AHK5(RD) via a prominent hydrogen bond docking ridge and a
      hydrophobic patch. These features are conserved among all AHP proteins, but
      differ significantly from other structurally characterized prokaryotic and
      eukaryotic HPs. Surface plasmon resonance experiments show that AHK5(RD) binds to
      AHP1-3 with similar, micromolar affinity, consistent with the transient nature of
      this signaling complex. Our correlation of structural and functional data provide
      the first insight, at the atomic level as well as with quantitative affinity
      data, into the molecular recognition events governing the MSP in plants.

PMID- 23132143
TI  - Characterization of ion contents and metabolic responses to salt stress of
      different Arabidopsis AtHKT1;1 genotypes and their parental strains.
AB  - Plants employ several strategies to maintain cellular ion homeostasis under
      salinity stress, including mediating ion fluxes by transmembrane transport
      proteins and adjusting osmotic pressure by accumulating osmolytes. The HKT (high
      affinity potassium transporter) gene family comprises Na(+) and Na(+)/K(+)
      transporters in diverse plant species, with HKT1;1 as the only member in
      Arabidopsis thaliana. Cell-type-specific overexpression of AtHKT1;1 has been
      shown to prevent shoot Na(+) overaccumulation under salinity stress. Here, we
      analyzed a broad range of metabolites and elements in shoots and roots of
      different AtHKT1;1 genotypes and their parental strains before and after salinity
      stress, revealing a reciprocal relationship of metabolite differences between an
      AtHKT1;1 knockout line (hkt1;1) and the AtHKT1;1 overexpressing lines (E2586 UAS
      GAL4 :HKT1;1 and J2731*UAS GAL4 :HKT1;1). Although levels of root sugars were
      increased after salt stress in both AtHKT1;1 overexpressing lines, E2586 UAS GAL4
      :HKT1;1 showed higher accumulation of the osmoprotectants trehalose, gentiobiose,
      and melibiose, whereas J2731*UAS GAL4 :HKT1;1 showed higher levels of sucrose and
      raffinose, compared with their parental lines, respectively. In contrast, the
      knockout line hkt1;1 showed strong increases in the levels of the tricarboxylic
      acid (TCA) cycle intermediates in the shoots after salt treatment. This coincided
      with a significant depletion of sugars, suggesting that there is an increased
      rate of carbon influx into the TCA cycle at a constant rate of C-efflux from the
      cycle, which might be needed to support plant survival during salt stress. Using
      correlation analysis, we identified associations between the Na(+) content and
      several sugars, suggesting that regulation of sugar metabolism is important in
      plant responses to salinity stress.

PMID- 23132144
TI  - A combination of micronucleus assay and fluorescence in situ hybridization
      analysis to evaluate the genotoxicity of formaldehyde.
AB  - A genotoxic effect of formaldehyde (FA), particularly micronucleus (MN)
      induction, has been shown in several previous studies. The aim of the present
      study was to assess the frequency of micronuclei and to identify the type of
      chromosomal damage in Tunisian staff members working in the Pathologic Anatomy
      Laboratory of Farhat Hached hospital (Sousse, Tunisia) who were exposed to FA.
      Assessment of chromosomal damage was performed in peripheral lymphocytes of 31 FA
      exposed employees compared with 31 control employees working in the
      administrative department of the same hospital. The clastogenic/aneugenic effect
      of FA was evaluated using the standard MN assay in combination with fluorescence
      in situ hybridization (FISH) using pan-centromeric probes. The mean level of
      exposure to FA was 3.4 ppm. The results showed a significant increase of MN
      frequency in lymphocytes of exposed workers compared with the control group
      (25.35 +/- 6.28 0/00 vs. 7.08  +/- 4.62 0/00, p < 0.05). As assessed by FISH, the
      frequency of centromeric micronuclei (C+MN) was greater in exposed subjects than
      in controls (18.38 +/- 5.94 0/00 vs. 5.03 +/- 3.64 0/00). Among the C+MN, the
      frequency of MN containing one centromere (C1+MN) was significantly greater in
      pathologists and anatomists than in controls (15.35 +/- 6.0 0/00 vs. 3.33 +/-
      2.74 0/00, p < 0.05). The results showed an effect of sex and time of FA exposure
      with significantly increased frequencies of all end points measuring aneuploidy
      (C+MN, C1+MN, and Cx+MN [more then one MN]). The increased frequency of C1+MN
      observed in the exposed group may suggest a slight aneugenic effect of FA
      exposure.

PMID- 23132145
TI  - Experimental and theoretical studies of hydroxyl-induced magnetism in TiO
      nanoclusters.
AB  - A main challenge in understanding the defect ferromagnetism in dilute magnetic
      oxides is the direct experimental verification of the presence of a particular
      kind of defect and distinguishing its magnetic contributions from other defects.
      The magnetic effect of hydroxyls on TiO nanoclusters has been studied by
      measuring the evolution of the magnetic moment as a function of moisture exposure
      time, which increases the hydroxyl concentration. Our combined experiment and
      density-functional theory (DFT) calculations show that as dissociative water
      adsorption transforms oxygen vacancies into hydroxyls, the magnetic moment shows
      a significant increase. DFT calculations show that the magnetic moment created by
      hydroxyls arises from 3d orbitals of neighboring Ti sites predominantly from the
      top and second monolayers. The two nonequivalent hydroxyls contribute differently
      to the magnetic moment, which decreases as the separation of hydroxyls increases.
      This work illustrates the essential interplay among defect structure, local
      structural relaxation, charge redistribution, and magnetism. The microscopic
      differentiation and clarification of the specific roles of each kind of intrinsic
      defect is critical for the future applications of dilute magnetic oxides in
      spintronic or other multifunctional materials.

PMID- 23132146
TI  - Which patients with advanced cancer and biliary obstruction benefit from biliary
      stenting most? An analysis of prognostic factors.
AB  - BACKGROUND: Patients with advanced cancer may present with obstructive jaundice.
      Biliary stenting is the treatment of choice. However, which patients benefit most
      is not well-defined, yet. Our aim was to delineate the clinical factors affecting
      prognosis. MATERIAL AND METHODS: Charts of 140 patients with advanced cancer who
      underwent biliary stenting were retrospectively analyzed. Their median age was
      63.5 years. Of these patients, 73 (52.1 %) were male, 32 (22.9 %) had ECOG PS 1
      and 81 (57.9 %) had PS 2. The most frequent cancer types were cholangiocellular
      cancer (64, 45.7 %) and pancreatic cancer (36, 25.7 %). RESULTS: Median overall
      survival (OS) was 141 (95 % CI, 100.7-185.3) days. Female patients lived longer
      (161.0 vs. 124.0 days) (p = 0.036). Those patients with colorectal cancer lived
      the longest (667.0 days), followed by cholangiocellular (211.0 days), and gastric
      cancers (106.0 days) (p = 0.004). The distribution of primary diagnosis differed
      significantly between sexes: cholangiocellular cancer was present in 22 (30.1 %)
      out of 73 men and 42(62.7 %) out of 67 women (chi-square p < 0.001). There was a
      trend for longer overall survival if ALT (p = 0.08) and AST (p = 0.06) were
      normalized after stent insertion. Of the 137 patients, 63 (45.5 %) did not
      experience any complication. In 74 patients with complications, there were 39
      (28.5 %) episodes of cholangitic infections and 35 (25.5 %) biliary obstructions.
      In three patients, we could not find data on infections. CONCLUSION: Underlying
      malignancy, hence the natural biology and the therapeutic expectations are
      probably the most important factors which must be considered during decision
      making.

PMID- 23132147
TI  - Natural torsion in chiral single-wall carbon nanotubes.
AB  - Optimizations performed with two geometrical, molecular mechanical and density
      functional models show that the configuration of single-wall carbon nanotubes is
      slightly twisted with respect to that predicted by conventional techniques.
      Geometrical models are used to explain the effect by breaking of local symmetry
      of the equally distant neighbors in graphene in the course of rolling, which is
      minimized by torsion. The torsion angle is small, and decreases with nanotube
      diameter, being less than 1 degrees  A(-1) for ultrathin tubes. Therefore this
      effect can be hard to observe in experiments. Still, we single out features in
      diffraction patterns which can distinguish between twisted and non-twisted
      configurations. In addition, torsion makes a blue shift in the radial breathing
      mode, which for thin tubes can be seen by Raman measurement. The effect is
      slightly strengthened at room temperature.

PMID- 23132148
TI  - Parkinson's disease and osteoporosis.
AB  - BACKGROUND: patients with Parkinson's disease (PD) have a high risk of sustaining
      osteoporotic fractures as a result of falls and reduced bone mass. OBJECTIVE: to
      summarise the underlying pathophysiological mechanisms of bone loss in PD by
      reviewing the available literature. METHODS: a Medline search was performed for
      articles published between January 1975 and January 2011, using the keywords
      'bone mineral density', 'bone loss', 'bone metabolism', 'osteoporosis',
      'osteopenia', 'Parkinson's disease' and 'Parkinsonism'. RESULTS: PD patients have
      a lower bone mineral density (BMD) than age-matched controls. Bone loss in PD is
      multifactorial, resulting from immobility, decreased muscle strength, and low
      body weight. Vitamin D deficiency is also important, not only because it reduces
      BMD, but also because cell function in the substantia nigra depends on vitamin D.
      Lastly, hyperhomocysteinaemia, an independent risk factor for osteoporosis, is
      common in PD, due to levodopa use, as well as vitamin B12 and folic acid
      deficiency. A few studies have demonstrated that treatment with bisphosphonates,
      vitamin D and calcium can increase BMD and reduce fractures in PD patients.
      CONCLUSION: bone loss in PD is multifactorial. It is clinically important because
      of the concomitant risk of fractures. Screening for osteoporosis should be
      considered more often, and therapeutic interventions should be initiated.

PMID- 23132149
TI  - Shared decision making needs a care perspective.

PMID- 23132150
TI  - Concordance rates of birth defects after assisted reproductive technology among
      17 258 Japanese twin pregnancies: a nationwide survey, 2004-2009.
AB  - BACKGROUND: Most twins after assisted reproductive technology (ART) are
      dizygotic. Analysis of dizygotic twin pairs is useful in assessing familial
      aggregation in the development of birth defects. METHODS: Using nationwide post
      ART data from the Japan Society of Obstetrics and Gynecology, recurrence risk
      ratios (RRRs)-defined as probandwise concordance rates of birth defects in twins
      divided by the prevalence of birth defects in the general population-were
      calculated as indicators of familial aggregation. Birth defects were then
      reclassified according to the ICD-10 categories corresponding to codes Q00-Q99.
      From 2004 to 2009, there were 17 258 twin pregnancies. RESULTS: At least 1 birth
      defect was noted in 236 twin pairs: 11 concordant and 225 discordant pairs.
      Regarding major organ systems, high probandwise concordance rates were observed
      for congenital malformations of eye, ear, face, and neck (11.8%), cleft lip and
      cleft palate (10.5%), congenital malformations of the nervous system (9.8%), and
      other congenital malformations of the digestive system (9.5%). High RRRs were
      observed for congenital malformations of eye, ear, face, and neck (RRR = 233),
      specifically other congenital malformations of the ear (RRR = 449); congenital
      malformations of the great arteries (RRR = 235), specifically those of the patent
      ductus arteriosus (RRR = 530); and for cleft lip and cleft palate (RRR = 208),
      specifically cleft palate with cleft lip (RRR = 609). The probandwise concordance
      rate of any birth defect (8.9%) was nearly identical to the approximated
      recurrence risk of sib-pairs (8.8%), which assumed multifactorial inheritance.
      CONCLUSIONS: The present findings suggest that familial aggregation is a factor
      in some birth defects.

PMID- 23132152
TI  - Footfall placement variability and falls in multiple sclerosis.
AB  - Gait variability (i.e., fluctuations in walking) provides unique information
      about the control of movement and is associated with falls. This investigation
      examined the association between gait variability and falls in persons with
      multiple sclerosis (MS) and healthy controls. Traditional distributional metrics
      of gait variability (i.e., coefficient of variation (CV)) and a novel metric
      based on Fourier series analysis of footfall placement variability were
      determined for 41 individuals with MS and 20 age- and sex-matched controls.
      Spatiotemporal parameters of gait were collected using a 7.9 m electronic walkway
      that recorded individual footfalls during steady state comfortable walking.
      Persons with MS were divided into two groups based on fall history (non-fallers
      and recurrent fallers). Overall, persons with MS had greater gait variability
      than controls as indexed by CV and Fourier-based variability (p's < 0.05).
      Moreover, recurrent fallers with MS had greater Fourier-based variability than
      non-fallers with MS (p = 0.025), whereas there was no difference in MS groups in
      traditional gait variability metrics (p > 0.05). These observations highlight
      that footfall placement variability is related to fall status in MS. Future work
      determining the sensitivity of footfall placement variability to dysfunction is
      warranted.

PMID- 23132151
TI  - Comparisons of planar and tubular biaxial tensile testing protocols of the same
      porcine coronary arteries.
AB  - To identify the orthotropic biomechanical behavior of arteries, researchers
      typically perform stretch-pressure-inflation tests on tube-form arteries or
      planar biaxial testing of splayed sections. We examined variations in finite
      element simulations (FESs) driven from planar or tubular testing of the same
      coronary arteries to determine what differences exist when picking one testing
      technique vs. another. Arteries were tested in tube-form first, then tested in
      planar-form, and fit to a Fung-type strain energy density function. Afterwards,
      arteries were modeled via finite element analysis looking at stress and
      displacement behavior in different scenarios (e.g., tube FESs with tube- or
      planar-driven constitutive models). When performing FESs of tube inflation from a
      planar-driven constitutive model, pressure-diameter results had an error of 12.3%
      compared to pressure-inflation data. Circumferential stresses were different
      between tube- and planar-driven pressure-inflation models by 50.4% with the
      planar-driven model having higher stresses. This reduced to 3.9% when rolling the
      sample to a tube first with planar-driven properties, then inflating with tubular
      driven properties. Microstructure showed primarily axial orientation in the
      tubular and opening-angle configurations. There was a shift towards the
      circumferential direction upon flattening of 8.0 degrees . There was also
      noticeable collagen uncrimping in the flattened tissue.

PMID- 23132153
TI  - [Does hypoglycaemia increase mortality risk in critical ill patients? Intensive
      insulin treatment is only recommended in clinical trials].

PMID- 23132154
TI  - [Regional analysis of drug treatment prevalence and medication  of diabetes
      mellitus in Germany].
AB  - BACKGROUND AND AIM: Diabetes mellitus is a widespread chronic disease. Diabetes
      prevalence was already analyzed in multiple complex studies. The goal of this
      analysis was the determination of the regional drug treatment prevalence and
      medication of diabetes mellitus in Germany. Simultaneously, we examined and
      validated the applicability of prescription data of the German statutory health
      insurance (SHI) as the basis for reliable and comparable prevalence estimations.
      PATIENTS AND METHODS: For the analysis, we used anonymized data from a
      prescription database as well as the member statistics of the German federal
      Ministry of Health. By using defined prescription profiles with anti-diabetic
      medication, we determined the diabetic patients and treatment schemes per
      Association of SHI Physicians. Subsequently, we calculated and described the drug
      treatment prevalence and medication. A differentiation between type 1 and type 2
      diabetes was not possible. RESULTS: The total prevalence of drug-treated patients
      in Germany was 7.77%. The regional values ranged from 6.40% in Schleswig-Holstein
      until 11.37% in Saxony-Anhalt. The highest numbers of drug treatment prevalence
      were found in the East of Germany. Insulin treatment was frequent in Hamburg, but
      rare in Bavaria. Insulin combined with oral anti-diabetic medication was mainly
      dispensed in Saxony-Anhalt and Brandenburg, least in Hamburg. A treatment with
      one or more oral anti-diabetics was most common in Bavaria and Bremen, lowest in
      Rhineland-Palatinate and Mecklenburg-West Pomerania. CONCLUSION: We developed an
      easy to use evaluation algorithm for prescription data to estimate the drug
      treatment prevalence of a chronic disease. The estimated prevalence confirms the
      increasing trend reported from other studies and appears to be plausible in
      comparison. More research is required to validate and enhance the method.

PMID- 23132155
TI  - [Hantavirus infection due to Dobrava-Belgrade virus in a third trimester pregnant
      woman].
AB  - HISTORY AND ADMISSION FINDINGS: A 20-year-old woman was admitted to our hospital
      because of acute renal failure. She was pregnant in the third trimester. She
      reported on nausea, feeling of sickness, vomiting, abdominal pain and
      consecutively gross hematuria and sinustachycardia. Under suspicion of premature
      labour the patient was admitted to an external hospital. An antibiotic therapy
      with intravenous ampicillin/sulbactam was initiated. Because of acute kidney
      injury the patient was transferred firstly to the university women's hospital and
      finally to the department of nephrology. Obesity, the clinical signs of
      pregnancy, dehydration and small edema of the lower legs were the main medical
      findings on examination. INVESTIGATIONS: Laboratory tests revealed hyperuricemia,
      virological tests detected an acute infection with Dobrava-Belgrade virus. The
      ultrasonography demonstrated a pregnancy in good condition and a dilated
      (physiological) renal pelvis but otherwise normal renal morphology. DIAGNOSIS,
      TREATMENT AND COURSE: A Hantavirus associated acute kidney failure due to
      infection with the Dobrava-Belgrade virus was diagnosed. The course of the acute
      renal failure was characterised by remission of all symptoms. Intermittent
      evaluation by an obstetrician and a nephrologist were done to diagnose maternal
      and/or fetal complications. A renal replacement therapy was not necessary. At the
      41st week of gestation a healthy male infant was born. The development of the
      newborn was age-appropriate. CONCLUSION: Hantavirus infections should be
      considered in cases of pregnancy-associated acute kidney injury.

PMID- 23132156
TI  - [82-year-old woman with progressive abdominal pain and vomiting].

PMID- 23132157
TI  - [Familial hypercholesterolemia].
AB  - Familial hypercholesterolemia is one of the most common hereditary metabolic
      disorders, untreated with grave cardiovascular consequences. A general
      practitioner will see at least one affected individual each month, but will
      rarely be aware of the diagnosis, though it is easily suspected: an LDL
      cholesterol >= 190 mg/dl, a family history of premature cardiovascular disease,
      or clinical signs as arcus lipoides, tendinous xanthomata, or a thickened
      Achilles' tendon must draw the attention to familial hypercholesterolemia.
      Because of the burden of high cholesterol levels from childhood on therapy should
      be initiated early enough, which has become greatly ameliorated since the
      introduction of statins. In conjunction with additional risk factors, notably low
      HDL-cholesterol or elevated lipoprotein(a) the cardiovascular sequelae can be
      dramatic and may call for more intense therapies. However, often the routine of
      successful cholesterol lowering covers the diagnosis nowadays, so that a
      heritable metabolic disorder is not suspected, which, however, prevents an
      effective prevention in relatives, particularly the children of the patient.

PMID- 23132158
TI  - [Acceptability and practicability of quality criteria for  self-help related
      patient centredness].

PMID- 23132159
TI  - [Vitamin D and innate immunity of the skin].
AB  - Besides its role in bone metabolism vitamin D is involved in important regulatory
      mechanisms within the innate and adaptive immune system. In particular, vitamin D
      affects the production of antimicrobial peptides (AMPs). AMPs are endogenous
      'antibiotics', produced my man himself with further immune regulatory functions
      in the skin and other epithelial surfaces. AMPs play a central role in the
      pathogenesis of several inflammatory skin diseases such as atopic eczema or
      psoriasis. Therefore, the vitamin D signal pathway could serve as a treatment
      target for those diseases. In this review we discuss the role of the vitamin D
      signalling pathway in the context of innate immunity in inflammatory skin
      diseases.

PMID- 23132160
TI  - [Diagnosis, implication, prevention and treatment of microalbuminuria].

PMID- 23132162
TI  - [Are muscle vein thrombosis comparable to deep calf vein thrombosis?].

PMID- 23132163
TI  - Breast milk jaundice:  effect of bacteria present in breast milk and infant
      feces.
AB  - OBJECTIVE: Breast milk is an important source of bacteria in establishing the
      infantile intestinal microbiota that appear to influence the enterohepatic
      circulation of bilirubin. The aim of the present study was to evaluate the effect
      of breast milk's microbiological content on the development of breast milk
      jaundice (BMJ). METHODS: A total number of 60 mother-infant pairs enrolled to the
      study. Two groups were defined: BMJ group (n=30), full-term otherwise healthy
      newborns who were considered BMJ; control group (n=30), full-term healthy
      newborns without jaundice. All newborns in the study were exclusively breast-fed.
      The breast milk samples and the feces of infants were evaluated for content of
      selected bacterial populations (Bifidobacterium, Lactobacillus, Clostridium,
      Staphylococcus, and Streptococcus species) with real-time polymerase chain
      reaction. RESULTS: Bifidobacterium bifidum content in the breast milk and B
      adolescentis, B bifidum, and B longum content in the fecal samples were higher in
      the control group than in the BMJ group. The milk and fecal concentrations of B
      bifidum were significantly correlated. The concentrations of breast milk B
      bifidum and fecal B bifidum, B adolescentis, and B longum were found to be
      negatively correlated with bilirubin levels. CONCLUSIONS: Our results suggest
      that Bifidobacterium species in breast milk may protect against BMJ.

PMID- 23132164
TI  - Urea C-13 test is not enough to diagnose a Helicobacter pylori infection.

PMID- 23132165
TI  - Antigen presentation by eosinophils in eosinophilic esophagitis?

PMID- 23132166
TI  - Response to hepatitis A and B vaccination in pediatric patients with celiac
      disease.
AB  - OBJECTIVES: The aim of the study was to evaluate the response to hepatitis A and
      B vaccinations in pediatric patients with celiac disease (CD). METHODS: Thirty
      patients with CD ages 1 to 15 years were compared with 50 healthy age-, sex-, and
      body mass index-matched controls. Screening for hepatitis A and B serology was
      carried out before vaccination. Susceptible cases received 20 MUg of recombinant
      DNA vaccine for hepatitis B (0,1, and 6 months) and 720 milliELISA units of
      inactivated hepatitis A virus (HAV) vaccine (0 and 6 months). Postvaccination
      serologic evaluation was performed 1 month after the last dose of primary
      vaccination, 1 month after the booster dose, and once every year during follow
      up. RESULTS: Sixteen patients and 35 controls received hepatitis A vaccine;
      protective anti-HAV antibodies were developed in 12 (75%) of the patients and all
      of the controls (75% vs 100%, respectively; 95% confidence interval [CI] 0.47
      0.92, P=0.007). Thirty patients and 50 controls received hepatitis B vaccine, and
      70% of the patients vs 90% of the controls achieved seroprotection (anti-HBs
      titers >=10 mIU/mL) 1 month after primary vaccination (95% CI 0.74-0.90, P=0.03).
      Four patients were unresponsive to both of the vaccines. The overall
      seroprotection rates were 96% in controls and 80% in patients after the whole
      hepatitis B vaccination series (95% CI 0.04-0.18, P=0.04). No significant
      reduction was observed in antibody response among patients and controls during
      follow-up period. CONCLUSIONS: The rate of seroconversion to the hepatitis B
      virus- and HAV vaccine is lower in patients with CD than in healthy controls.

PMID- 23132167
TI  - Vaccinations in celiac disease.

PMID- 23132168
TI  - Inflamm-ageing.
AB  - PURPOSE OF REVIEW: Inflamm-ageing, defined as the chronic low-grade inflammation
      typical of ageing, seems to be the common biological factor responsible for the
      decline and the onset of disease in the elderly. The major age-related diseases
      share a common inflammatory pathogenesis, giving rise to the so-called 'diseasome
      of inflamm-ageing'. Main objective of this review is to provide a comprehensive
      view of the complex interactions responsible for inflamm-ageing, underlining its
      relationship with metaflammation and the role of senescent cells, gut microbiota
      and nutrition in determining when, where and how much this phenomenon impacts on
      the health status during human lifespan. RECENT FINDINGS: The ageing process and
      the health status of elderly people may be improved by facing and slowing down
      inflamm-ageing. Among the inflammation modulators, gut microbiota and nutrition
      should be exploited as potential powerful tools to promote healthy ageing and to
      extend the lifespan in humans. SUMMARY: The possibility to control inflamm-ageing
      represents a powerful tool to modulate and counteract the major age-related
      pathologies and it is urgent to clarify the shady areas of the complex mechanisms
      underpinning inflamm-ageing in order to carry out targeted therapeutic
      interventions towards an improvement of the health status in the elderly
      population.

PMID- 23132169
TI  - Amino acids:  the most versatile nutrients.

PMID- 23132170
TI  - The potential effects of pomegranate (Punica granatum) juice on carbon
      tetrachloride-induced nephrotoxicity in rats.
AB  - The purpose of this study was to evaluate the effect of pomegranate (Punica
      granatum) in inhibiting and reversing the nephrotoxicity of carbon tetrachloride,
      a potent oxidative stress inducer which induces cellular kidney damage. Rats were
      intraperitoneally injected with carbon tetrachloride (2 mL/kg body weight) which
      produced severe renal tissue damage, as demonstrated by decreased uric acid and
      dramatic elevation of urea and creatinine. In addition, carbon tetrachloride
      injection caused oxidative stress in rats, as evidenced by increased lipid
      peroxidation and nitrite/nitrate (NO x ) concentrations in the renal tissue,
      along with a remarkable reduction in superoxide dismutase, catalase, glutathione
      transferase, glutathione reductase, glutathione peroxidase activities and
      glutathione content. We suggested that pomegranate juice was able to elevate the
      antioxidant defense system, clean up free radicals, lessen oxidative damages and
      protect the kidney against carbon tetrachloride-induced toxicity, thus having a
      potential protective effect.

PMID- 23132171
TI  - Male genital premalignant dermatoses.
AB  - The spectrum of conditions affecting the penile skin is varied and ranges from
      simple, benign dermatoses to premalignant and malignant conditions. Recently,
      improved understanding of the aetiology and natural history of these conditions
      has shaped new treatment paradigms and a functional knowledge of dermatology,
      urology and genitourinary medicine is required to successfully diagnose and treat
      these men. In this article, we explore the common precancerous states that can
      lead to penile carcinoma and review the recent advances with regards to the
      molecular basis for these dermatoses and the treatments that may be most
      effective for these men.

PMID- 23132172
TI  - A dual point-of-care test shows good performance in simultaneously detecting
      nontreponemal and treponemal antibodies in patients with syphilis: a multisite
      evaluation study in China.
AB  - BACKGROUND: Rapid point-of-care (POC) syphilis tests based on simultaneous
      detection of treponemal and nontreponemal antibodies (dual POC tests) offer the
      opportunity to increase coverage of syphilis screening and treatment. This study
      aimed to conduct a multisite performance evaluation of a dual POC syphilis test
      in China. METHODS: Participants were recruited from patients at sexually
      transmitted infection clinics and high-risk groups in outreach settings in 6
      sites in China. Three kinds of specimens (whole blood [WB], fingerprick blood
      [FB], and blood plasma [BP]) were used for evaluating sensitivity and specificity
      of the Dual Path Platform (DPP) Syphilis Screen and Confirm test using its
      treponemal and nontreponemal lines to compare Treponema pallidum particle
      agglutination (TPPA) assay and toluidine red unheated serum test (TRUST) as
      reference standards. RESULTS: A total of 3134 specimens (WB 1323, FB 488, and BP
      1323) from 1323 individuals were collected. The sensitivities as compared with
      TPPA were 96.7% for WB, 96.4% for FB, and 94.6% for BP, and the specificities
      were 99.3%, 99.1%, and 99.6%, respectively. The sensitivities as compared with
      TRUST were 87.2% for WB, 85.8% for FB, and 88.4% for BP, and the specificities
      were 94.4%, 96.1%, and 95.0%, respectively. For specimens with a TRUST titer of
      1:4 or higher, the sensitivities were 100.0% for WB, 97.8% for FB, and 99.6% for
      BP. CONCLUSIONS:  DPP test shows good sensitivity and specificity in detecting
      treponemal and nontreponemal antibodies in 3 kinds of specimens. It is hoped that
      this assay can be considered as an alternative in the diagnosis of syphilis,
      particularly in resource-limited areas.

PMID- 23132174
TI  - CO2 capture in aqueous ammonia solutions: a computational chemistry perspective.
AB  - Twenty-five transition structures (TS's) for CO(2) fixation by up to four base
      molecules (ammonia or ammonia + water) were located using M06-2X/6-311++G(d,p).
      All lead to either carbamate (NH(2)CO(2)(-)) or bicarbonate (HCO(3)(-)) products.
      Single-point energies at CCSD(T)/maug-cc-pVTZ//M06-2X/6-311++G(d,p) were added to
      SM8/M06-2X/6-311++G(d,p) energies to obtain best-estimate aqueous activation
      energies. All theories agree that: (i) NH(2)CO(2)(-) formation has a lower free
      energy of activation (best est. 44-45 kJ mol(-1)) than HCO(3)(-) formation (best
      est. 86 kJ mol(-1)), and (ii) free energies of activation for CO(2) fixation are
      lowered when an ammonia molecule accepts the proton from the nucleophilic base.
      The theory also supports a key role for ammonium ions in the observed
      decomposition of NH(2)CO(2)(-) near pH 9.

PMID- 23132173
TI  - Freiburg neuropathology case conference: widespread mass lesions after resection
      of a glioblastoma multiforme.

PMID- 23132175
TI  - Synthesis and rac-lactide ring-opening polymerisation studies of new alkaline
      earth tetrahydroborate complexes.
AB  - Reaction of K[HC(C(Me)NAr')(2)] (Ar' = 2,6-C(6)H(3)(i)Pr(2)) with Mg(BH(4))(2)
      afforded the pseudo four-coordinate tetrahydroborate complex
      Mg{HC(C(Me)NAr')(2)}(BH(4))(THF) (1). The corresponding reaction of
      Ca(BH(4))(2)(THF)(2) or Sr(BH(4))(2)(THF)(2) gave the pseudo five-coordinate
      analogues M{HC(C(Me)NAr')(2)}(BH(4))(THF)(2) (M = Ca (2) or Sr (3)). All three
      compounds 1-3 have been structurally characterised. According to X-ray
      crystallography and IR spectroscopy all possess kappa(3)-bound BH(4) ligands in
      the solid state. This coordination mode is also maintained in THF solution for 2
      and 3, whereas complex 1 appears to form a bis(THF) complex containing a kappa(2)
      bound BH(4). Reaction of 1 with K[HC(P(Ph(2))NAr')(2)](THF)(2) formed
      Mg{HC(P(Ph(2))NAr')(2)}(BH(4))(THF)(2) (4) possessing a kappa(3)-bound BH(4)
      ligand in both the solid state and solution. Compounds 1, 2 and 4 are highly
      active for the ring-opening polymerisation of epsilon-caprolactone forming
      dihydroxytelechelic PCL. Compound 1 is also extremely active for the ROP of rac
      lactide forming highly heterotactic PLA with good agreement between predicted and
      measured M(n), in accord with previous studies of alkoxide and amide initiators
      based on this metal and ligand class. Compounds 2 and 4 were less productive and
      gave PLA with poorer control of M(n) and negligible heterotactic enrichment.
      MALDI-ToF MS analysis of the PLA formed with all three catalysts showed a mixture
      of both -CH(Me)CHO and -CH(Me)CH(2)OH termini arising from the M-BH(4) initiating
      groups.

PMID- 23132176
TI  - Size control of laser-fabricated surfactant-free gold nanoparticles with highly
      diluted electrolytes and their subsequent bioconjugation.
AB  - Size control of laser-fabricated surfactant-free gold nanoparticles is a
      challenging endeavor. In this work, we show that size control can be achieved by
      adding ions with low salinity during synthesis. In addition, this approach offers
      the opportunity to fundamentally study ion interactions with bare nanoparticle
      surfaces and can help to elucidate the nanoparticle formation mechanism. The
      studies were carried out in a flow-through reactor and in the presence of NaCl,
      NaBr and sodium phosphate buffer at minimal ionic strengths. A significant size
      quenching effect at ionic strengths from 1-50 MUM was found, which allowed
      surfactant-free nanoparticle size control with average diameters of 6-30 nm. This
      effect went along with low polydispersity and minimal aggregation tendencies and
      was confirmed by UV-vis spectroscopy, TEM, SEM and analytical disk
      centrifugation. Our findings indicate that size quenching originates from an
      anionic electrostatic stabilization depending on the nanoparticle surface area,
      which may be caused by specific ion adsorption. By subsequent delayed
      bioconjugation in liquid-flow using bovine serum albumin as a stabilizing agent,
      nano-bioconjugates with good stability in cell culture media were obtained, which
      are applicable in toxicology and cell biology.

PMID- 23132177
TI  - Summary of the ISPD Preconference Day, June 3, 2012, Miami Beach.

PMID- 23132178
TI  - Continuous cerebral and myocardial perfusion during one-stage repair for aortic
      coarctation with ventricular septal defect.
AB  - Controversy still exists concerning the use of deep hypothermic circulatory
      arrest (DHCA) and selective antegrade cerebral perfusion (SACP) for repair of
      aortic coarctation (CoA) with ventricular septal defect (VSD). This report
      therefore describes outcomes of patients undergoing continuous cerebral and
      myocardial perfusion (CCMP) under mild hypothermia compared with DHCA and SACP.
      Retrospective analysis was performed for 110 consecutive patients undergoing
      anatomic reconstruction of CoA with VSD closure between 1999 and 2011. Patients
      repaired under CCMP with mild hypothermia (32  degrees C) (group A, n = 60) were
      compared with those repaired under DHCA (18  degrees C) and SACP (group B, n =
      50). In group A, the single arterial cannula perfusion technique was used for 15
      patients (25 %), and the dual arterial cannula perfusion technique was used for
      45 patients (75 %). The preoperative data were similar in the two groups. Group A
      had no hospital mortalities, compared with two mortalities (4 %) in group B.
      Group A had shorter myocardial ischemic and cardiopulmonary times, fewer delayed
      sternal closures, a shorter time to extubation, lower postoperative lactate
      levels, and fewer patients with low cardiac output requiring extracorporeal
      membrane oxygenation or with multiorgan failure than group B. During the
      postoperative course, no clinical or electrical neurologic events occurred in
      either group. The mean follow-up period was 5.2 +/- 3.2 years for group A and 7.5
      +/- 3.1 years for group B (P = 0.048). One late death occurred in group B and no
      late deaths in group A. The actuarial survival for the two groups was similar
      (100 % for group A vs 96 % for group B; P = 0.264). The freedom from all types of
      cardiac reintervention was 96.7 % in group A and 89.6 % in group B (P = 0.688).
      All the patients were free of neurologic symptoms. The authors' perfusion
      strategy using CCMP with mild hypothermia for repair of CoA with VSD is feasible,
      safe, and associated with improved postoperative recovery and should be the
      method of choice.

PMID- 23132179
TI  - Perioperative management of pheochromocytoma and catecholamine-induced dilated
      cardiomyopathy in a pediatric patient.
AB  - Dilated cardiomyopathy resulting from pheochromocytoma-mediated catecholamine
      excess poses a unique challenge to heart failure management. Although early
      screening of patients with familial neoplastic syndromes at risk for
      pheochromocytoma may facilitate early resection, the resultant manifestations of
      prolonged catecholamine excess among patients with undiagnosed pheochromocytoma
      may lead to myocardial fibrosis with both systolic and diastolic dysfunction.
      Furthermore, the hemodynamic effects of catecholamine excess exacerbate the risks
      of perioperative hemodynamic instability in the setting of such myocardial
      depression. This report describes an approach to the perioperative care of a
      child who had pheochromocytoma and catecholamine-induced cardiomyopathy with
      ventricular dysfunction refractory to medical management. 

PMID- 23132180
TI  - A pilot study of the pleth variability index as an indicator of volume-responsive
      hypotension in newborn infants during surgery.
AB  - PURPOSE: The aim of this pilot study was to evaluate the diagnostic value of
      pleth variability index (PVI) to predict fluid responsiveness in newborn infants
      during surgery. METHODS: PVI was continuously recorded in 29 mechanically
      ventilated newborn infants during surgery, and episodes of clinically indicated
      volume expansion (VE) (>=10 ml/kg in <=15 min) administration were evaluated. The
      upper limit of the reference range for PVI in mechanically ventilated newborns
      was defined by the 95th percentile of all PVI values from hemodynamically stable
      infants. RESULTS: The upper limit of the reference range of PVI was 18 %. One
      hundred and three VEs were evaluated in 58 sufficient VE size (SVES) episodes and
      16 insufficient initial VE size (IVES) episodes requiring repeated VE; all but
      one fulfilled criteria of volume-responsive hypotension (VRH). The median
      (interquartile range) PVI value during arterial hypotension in the 73 episodes
      with VRH was 23 % (20-25 %); postvolume PVI was 16 % (13-18 %). In 63 of 73 VRH
      episodes, during-hypotension PVI values were >18 % (86 % sensitivity for VRH).
      The median intermediate PVI, measured between VE in IVES episodes, was
      significantly higher than post-VE PVI in SVES episodes [18 % (16-21 % vs. 16 %
      (13-18 %]. CONCLUSION: This preliminary evaluation shows that PVI may indicate
      VRH in newborn infants during surgery.

PMID- 23132181
TI  - Influence of administration of 1 % glucose solution on neonatal blood glucose
      concentration in cesarean section.
AB  - Perioperative administration of adequate glucose prevents hypercatabolism.
      However, excessive glucose administration until delivery of a fetus might cause
      newborn hypoglycemia in cesarean section. In this retrospective study, we
      investigated whether the administration of 1 % glucose solution during cesarean
      section influenced neonatal blood glucose concentration. We found 46 consecutive
      patients between 37 and 41 weeks of gestation who underwent cesarean section
      under combined epidural and spinal anesthesia. We divided the patients into two
      groups: those receiving 1 % glucose solution (group A, N = 23) and those
      receiving a solution without glucose (group B, N = 23) until delivery. We
      recorded umbilical cord blood glucose on delivery, neonatal blood glucose level 3
      h after delivery, and 1- and 5-min Apgar scores. The dose of glucose administered
      until delivery of fetus in group A was 3.6 +/- 1.7 mg/kg/min [mean +/- standard
      deviation (SD)] and that in group B 0 mg/kg/min. Umbilical cord blood glucose
      concentration on delivery of fetus in group A was significantly higher than that
      in group B (101 +/- 19 vs. 66 +/- 10 mg/dl; P < 0.0001). Neonatal blood glucose
      level 3 h after delivery was not significantly different between groups (90 +/-
      15 vs. 90 +/- 21 mg/dl; P = 0.96). The 1- and 5-min Apgar scores were similar
      between groups. In conclusion, administration of 1 % glucose solution in cesarean
      section might contribute to prevention of neonatal hypoglycemia.

PMID- 23132183
TI  - Professionalism in psychiatry and medicine: a hot topic.

PMID- 23132184
TI  - Depression and pain: often together but still a clinical challenge: a review.
AB  - Depression is a common mental disorder with various symptoms and often
      accompanied with unexplained painful physical symptoms. Patients, especially in
      primary care, often present only with somatic symptoms and depressed mood is
      overlooked. On the other hand, psychiatrists don't pay enough attention to
      somatic or painful symptoms in patients with depression. The connection between
      depression and accompanying painful physical symptoms is not completely
      understood although some common neurobiological pathways are proposed. To achieve
      good clinical outcome all depression symptoms should be recognized and treated.
      In this review we focus on painful physical symptoms which could not be explained
      by somatic illness or the intensity can not be explained by physical disease and
      are attributed to somatic symptoms of depression. The aim of this review is to
      provide the basic necessary information for clinicians/psychiatrists on
      depression with painful physical symptoms, presenting the terminology,
      epidemiology, differential diagnostics, neurobiological background, psycho-social
      aspects and treatment strategies.

PMID- 23132182
TI  - High-dose remifentanil increases blood pressure and heart rate mediated by
      sympatho-activation in conscious rats.
AB  - PURPOSE: The ultra-short-acting MU-opioid receptor agonist, remifentanil, is
      commonly used in clinical anesthesia; however, there are limited data about the
      hemodynamic effects of remifentanil itself without anesthetics. We investigated
      the effects of an ultra-short-acting MU-opioid receptor agonist, remifentanil, on
      cardiovascular and sympathetic function in conscious rats. METHODS: The mean
      arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity
      (RSNA) were recorded during continuous intravenous (i.v.) infusion of
      remifentanil at a moderate-dose (0.25 and 0.5 MUg/kg/min) and a high-dose (1.0
      and 2.0 MUg/kg/min) in conscious intact and sino-aortic denervated (SAD) rats.
      Baroreflex sensitivity was examined during remifentanil administration. Rats were
      administered saline or naloxone to assess the involvement of the MU-opioid
      receptor in the remifentanil-induced responses. RESULTS: High-dose remifentanil
      induced biphasic changes in MAP and HR. Mediated by sympatho-activation, these
      parameters increased after briefly decreasing once. Subpressor-dose remifentanil
      enhanced baroreflex sensitivity. Changes in MAP, HR, and RSNA induced by
      remifentanil were inhibited by naloxone. CONCLUSIONS: High-dose remifentanil
      decreases MAP and HR transiently and increases these parameters mediated by the
      activation of sympathetic nerve activity in conscious rats.

PMID- 23132185
TI  - A review of somatoform disorders in DSM-IV and somatic symptom disorders in
      proposed DSM-V.
AB  - Psychiatric care providers should be trained to use current changes in the
      somatoform disorders criteria. New diagnostic criteria for Somatic Symptom
      disorders in the proposed DSM-V is discussed and compared with its older
      counterpart in DSM-IV. A new category called Somatic Syndrome Disorders is
      suggested. It includes new subcategories such as "Complex Somatic Symptom
      Disorder" (CSSD) and "Simple Somatic Symptom Disorder" (SSSD). Some of the
      subcategories of DSM-IV derived disorders are included in CSSD. While there are
      some changes in diagnostic criteria, there are concerns and limitations about the
      new classification needed to be more discussed before implementation. Functional
      somatic disturbance, the counterpart of converion disorder in DSM-IV, can be
      highly dependet on the developmental level of children. However, the role of
      developmental level needs to be considered.

PMID- 23132186
TI  - Chronic illness and family: impact of schizophrenia and Crohn's disease on the
      family quality of life.
AB  - BACKGROUND: Quality of life assessments are increasingly present in health
      research. Chronic and progressive illness of a family member unavoidably affects
      quality of life of a family as a whole. The goals of this study were to gain
      insight into the family burden of chronic disorders, especially possible
      differences in family quality of life (FQOL) in families that have members
      suffering from either schizophrenia or Crohn's disease, and families in which
      none of the members have chronic somatic or mental illness, as well as to pilot
      an instrument for this purpose. SUBJECTS AND METHODS: The sample consisted of 53
      families with a member suffering from schizophrenia, 50 families with a member
      suffering from Crohn's disease, and 45 families with no identifiable chronic
      illnesses. An informant from each family underwent a structured face to face
      interview, using a questionnaire specially adapted from Family Quality of Life
      Survey, an instrument widely used to assess FQOL in families with members with
      disabilities, and which addresses nine areas of family life. RESULTS: In the
      domain of health, both groups of families with chronic illnesses believe they
      have significantly different conditions when compared to members of the Control
      group. In the Crohn's disease group, families had a great deal more of challenges
      in accessing healthcare services; and see themselves at a disadvantage when
      compared to both other groups in the domain of finances. Control group offered
      lowest rating in the domain of support from others. Overall measures of FQOL show
      significant variation among the three groups, Crohn's disease group offering
      lowest ratings, followed by families of mental health service users. CONCLUSIONS:
      Overall, FQOL seems to be lower in families that have members diagnosed with
      Crohn's disease than in families with members suffering from schizophrenia.
      Illness-specific studies are required, as well as instruments with stronger
      psychometric properties and studies of determinants of FQOL. Qualitative approach
      should be emphasised when studying FQOL related to chronic illnesses.

PMID- 23132187
TI  - Acute effects of progressive muscle relaxation on state anxiety and subjective
      well-being in chronic Bulgarian patients with schizophrenia.
AB  - BACKGROUND: Recently, there has been an interest in the relative effectiveness of
      progressive muscle relaxation (PMR) within the multidisciplinary treatment of
      patients with schizophrenia.The present study is aimed at providing evidence on
      the efficacy of PMR as means of alleviating the state anxiety and psychological
      distress and a way to increase subjective well-being in chronic patients with
      schizophrenia. SUBJECTS AND METHODS: Sixty four schizophrenia patients underwent
      2 sessions of PMR. On the third session they were randomly allocated to either
      the PMR or the reading control condition. The State Anxiety Inventory (SAI) was
      used to assess state anxiety and the Subjective Exercise Experience Scale (SEES)
      to assess psychological distress and subjective well-being before and after the
      third session for both groups. RESULTS: Our data show a significant time by group
      interaction for the SAI and SEES (Wilks lambda=0.58, p<0.001). Effect sizes for
      PMR were -0.22 (95%CI=-0.73 to 0.19) for state anxiety, -0.96 (95%CI=-0.41 to 
      1.43) for psychological stress, and +1.01 (95%CI=0.45 to 1.54) for subjective
      well-being. CONCLUSION: The present study provides scientific evidence for the
      utility of PMR in the chronic psychiatric settings for patients with
      schizophrenia.

PMID- 23132188
TI  - Attitude towards oneself and others in non-clinical population, depressed and
      paranoid examinees.
AB  - BACKGROUND: The theoretical concept of existential/life positions describes
      person's basic beliefs about oneself and others. Most of authors on TA postulated
      that every person has one of four possible basic life positions: I'm OK, you're
      OK; I'm not OK, you're OK; I'm OK, you're not OK and I'm not OK, you're not OK.
      The aim of this study was the authentication of Existential positions as
      theoretical concepts in Transaction Analysis, and it's potential to discriminate
      clinical from non-clinical examinees, and paranoid from depressive examinees
      within the clinical population. SUBJECTS AND METHODS: The research conducted was
      co-relational. The sample belongs to the convenience sample type, and comprised
      200 examinees, 100 from the non-clinical and 100 from the clinical population of
      adults. RESULTS: The results of the research confirm a statistically significant
      difference between the non-clinical and clinical part of the sample in the
      examined theoretical concept. The "I am not OK" existential position is more
      expressed in the clinical part of the sample. The differences between the
      examinees with depressive and paranoid disorders indicate that the examinees with
      the depressive disorder are more likely to express the "I am not OK, you are OK"
      and "I am not OK, you are not OK" Existential position. CONCLUSION: In general,
      we can infer that the assumptions which the research was aimed at testing
      received partial validation. Examinees from the clinical part of the sample have
      a statistically significantly higher score at the position "I am not OK".
      Examinees with depressive characteristics have a more pronounced "I am not OK,
      you are not OK" position.

PMID- 23132189
TI  - Sexual dysfunction in obsessive compulsive disorder and panic disorder.
AB  - BACKGROUND: Clinical research has provided conflicting evidence regarding sexual
      dysfunction in patients with OCD and PD. This study was undertaken to assess and
      compare certain parameters of sexual functioning in OCD and PD patients. SUBJECTS
      AND METHODS: The study population consisted of 80 patients between 20 and 60
      years of age with a diagnosis of OCD or PD who were followed and treated at the
      anxiety outpatient unit of Bakirkoy Research and Training Hospital for
      Psychiatric and Neurological Disorders between 2005 and 2006. The total study
      population comprised of 40 patients with OCD, 40 patients with PD, and 40 healthy
      volunteers as the control group. Of the two questionnaires used for study
      purposes, the first provided information on demographic data and certain
      parameters of sexual functioning, while the second was the validated Turkish
      translation of the Golombok-Rust Sexual Satisfaction Inventory with transliteral
      equivalence. RESULTS: Male subjects with OCD had a lower age of first
      masturbation and first nocturnal ejaculation. Infrequency problem among female
      and male patients with OCD occurred in 63.6% and 57.1%, respectively.
      Corresponding figures for PD patients were 36% and 38%. Thus, infrequency problem
      was more frequent among OCD patients. Sexual avoidance was found in 60.6% of
      female OCD patients and in 64% of female PD patients. Anorgasmia was detected in
      24.2% of the female subjects with OCD. CONCLUSION: Sexual dysfunction unrelated
      to pharmacotherapy has been found to occur in OCD and PD. Assessment of sexual
      functioning in these individuals before treatment may help prevent deterioration
      of sexual function that may occur upon introduction of psychotropic medications.

PMID- 23132190
TI  - Abused nurses take no legal steps: a domestic violence study carried out in
      eastern Turkey.
AB  - BACKGROUND: Our aim was to evaluate domestic violence among nurses in eastern
      Turkey. SUBJECTS AND METHODS: Ninety six (96) female nurses with an intimate
      partner were enrolled. Modified form of Abuse Assessment Screen Questionnaire was
      used. RESULTS: Twenty two (22.7%) of the participants reported domestic violence.
      None of them took legal steps. Most frequent domestic violence type was economic
      abuse (46%). Nurses, whose mothers were exposed to domestic violence, had
      significantly higher abuse rates. The abused group had also significantly higher
      smoking and miscarriage rates. CONCLUSIONS: Nurses need to be well informed for
      taking legal steps in case of domestic violence. Family history, smoking status
      and abortion rates may be further research focus for risk factors of domestic
      violence. Legal interventions should be optimized in order to encourage the
      victims to take legal steps.

PMID- 23132191
TI  - Traditional and online consumers in China: a preliminary study of their
      personality traits and decision-making styles.
AB  - BACKGROUND: Population of online consumers increases rapidly, but the decision
      making styles of online consumers and psychiatric denominators such as the
      personality correlates remain unclear. SUBJECTS AND METHODS: In 196 traditional,
      and 196 age-, education- and gender-matched online consumers, we have tested the
      Zuckerman-Kuhlman Personality Questionnaire (ZKPQ) and the Consumer Style
      Inventory (CSI). RESULTS: After exploratory and confirmatory factor analyses, we
      have defined a five-factor model CSI with 24 items. Online consumers scored lower
      on ZKPQ Neuroticism-Anxiety and higher on Aggression-Hostility than traditional
      ones did, and scored higher on CSI Novelty-fashion consciousness and Brand
      consciousness, and lower on Time consciousness than the traditional consumers
      did. ZKPQ Neuroticism-Anxiety was positively correlated with CSI Confused by
      overchoice in both groups, Sociability was positively correlated with Novelty
      fashion consciousness and negatively with Time consciousness in traditional
      group, and Impulsive Sensation Seeking was positively correlated with Novelty
      fashion consciousness and Time consciousness in online group. CONCLUSIONS: Our
      study suggests that, regarding the decision-making styles, online consumers
      display curiosity that lacks security and need other ways to improve their social
      lives. It also calls further designs to address the contributions of other
      psychiatric features to the particular decision-making styles in online
      consumers.

PMID- 23132192
TI  - Daily dose of 105 mg aripiprazole because of delusional origin: a case report.

PMID- 23132193
TI  - Quetiapine in management of manic symptoms in patient with heart transplantation:
      a case report.

PMID- 23132194
TI  - [The diagnosis "schizophrenia": past, present and future].
AB  - Schizophrenia is one of the most important diseases in psychiatry. The diagnostic
      criteria, first formulated more than 100 years ago, have since undergone multiple
      changes. While the disease was originally named "dementia praecox" by Emil
      Kraepelin, the term "schizophrenia" was coined by Eugen Bleuler soon afterwards.
      DSM-III changed diagnostic criteria dramatically in 1980, relying especially on
      Kurt Schneider's first rank criteria. These changes were also incorporated into
      ICD-10. Diagnosis of schizophrenia thus became much more reliable. Yet there
      remain many problems to be solved: the demarcation towards other psychotic
      disorders remains arbitrary; the diagnosis is based on multiple, quite different
      symptoms, enabling two patients being diagnosed with schizophrenia without
      sharing a single symptom, yet further important symptoms (e.g. cognitive
      impairments) are not even covered by present diagnostic criteria; until now it
      was not possible to formulate diagnostic criteria reflecting underlying
      biological processes or to find a reliable biological marker. These
      methodological uncertainties are in stark contrast to the persistence of the
      stigma which accompanies schizophrenia despite all efforts. For the forthcoming
      publication of DSM-5 and ICD-11 further revisions of diagnostic criteria of
      schizophrenia are to be expected.

PMID- 23132195
TI  - [Efficacy of integrated treatments for schizophrenia patients].
AB  - This article outlines two examples of cognitive-behavior group therapy approaches
      for an integrative treatment of psychosis: the Integrated Psychological Therapy
      (IPT) and the Integrated Neurocognitive Therapy (INT). We present their
      theoretical background, content and conceptualization as well as recent empirical
      evidence for their efficacy. The article concludes that adapting these approaches
      to early intervention for people with high risk of psychosis seems promising.

PMID- 23132196
TI  - [Recovery: reshaping scientific responsibilities].
AB  - Recovery-concepts have travelled from margin movements into mainstream psychiatry
      rapidly in recent years. Recovery advocacy has been joined by recovery research
      resulting in new information on the long-term perspectives of people experiencing
      severe mental health problems. Emerging data on recovery outcomes as well as
      processes bring on a paradigm shift from prognostic scepticism and focus on
      maintenance therapies towards an optimistic outlook and recovery-oriented
      interventions and services. The emerging evidence-base for recovery-orientation
      essentially includes the urgent call for a partnership approach allowing the full
      involvement of users and their families and friends and the exploit of their
      expertise. Patient self-determination, individual choice of flexible support and
      opportunities, intervenetions to promote empowerment and hope also in the long
      term, as well as assistance in situations of calculated risk are new indicators
      of quality of services. The dynamic complexities of recovery and resilience have
      the ability to capture the progress in biological, psychological, social and
      political advances in the direction of modern integrated and subject-oriented
      psychiatry. Cooperative and coordinated efforts together with consumers, carers,
      their spokespersons and public health advocates offer formidable chances to
      reduce stigma, discrimination and social exclusion, currently seriously limiting
      clinical and other efforts towards recovery.

PMID- 23132197
TI  - [Forensic aspects of schizophrenia].
AB  - Recent research has shown a clear association between schizophrenia and violent
      behaviour, which cannot be completely explained by co-morbid substance abuse or
      personality disorders. This increased risk for delinquent behaviour becomes
      apparent in acts of severe violent crime. Individuals who frequent the penal
      system often have a history of acute and chronic mental illness, as well as
      significant rates of co-morbidity; this includes alcohol and drug abuse, lack of
      motivation in therapy, poor insight regarding their illness, high rates of
      therapeutic non-compliance, as well as frequent, mostly short-term, contact with
      general psychiatry prior to forensic institutionalisation. Forensic psychiatric
      research has developed assessment and treatment tools which are also of great
      practical importance to general psychiatry.

PMID- 23132198
TI  - The association of complementary and alternative medicine use and health care
      expenditures for back and neck problems.
AB  - BACKGROUND: Health care costs associated with use of complementary and
      alternative medicine (CAM) by patients with spine problems have not been studied
      in a national sample. OBJECTIVES: To estimate the total and spine-specific
      medical expenditures among CAM and non-CAM users with spine problems. RESEARCH
      DESIGN: Analysis of the 2002-2008 Medical Expenditure Panel Survey. SUBJECTS:
      Adults (above 17 y) with self-reported neck and back problems who did or did not
      use CAM services. MEASURES: Survey-weighted generalized linear regression and
      propensity matching to examine expenditure differences between CAM users and non
      CAM users while controlling for patient, socioeconomic, and health
      characteristics. RESULTS: A total of 12,036 respondents with spine problems were
      included, including 4306 (35.8%) CAM users (40.8% in weighted sample). CAM users
      had significantly better self-reported health, education, and comorbidity
      compared with non-CAM users. Adjusted annual medical costs among CAM users was
      $424 lower (95% confidence interval: $240, $609; P<0.001) for spine-related
      costs, and $796 lower (95% confidence interval: $121, $1470; P = 0.021) for total
      health care cost than among non-CAM users. Average expenditure for CAM users,
      based on propensity matching, was $526 lower for spine-specific costs (P<0.001)
      and $298 lower for total health costs (P = 0.403). Expenditure differences were
      primarily due to lower inpatient expenditures among CAM users. CONCLUSIONS: CAM
      users did not add to the overall medical spending in a nationally representative
      sample with neck and back problems. As the causal associations remain unclear in
      these cross-sectional data, future research exploring these cost differences
      might benefit from research designs that minimize confounding.

PMID- 23132200
TI  - Person-centered care practices and quality in Department of Veterans Affairs
      nursing homes: is there a relationship?
AB  - OBJECTIVE: To examine variation in culture change to a person-centered care (PCC)
      model, and the association between culture change and a composite measure of
      quality in 107 Department of Veterans Affairs nursing homes. METHODS: We examined
      the relationship between a composite quality measure calculated from 24 quality
      indicators (QIs) from the Minimum Data Set (that measure unfavorable events), and
      PCC summary scores calculated from the 6 domains of the Artifact of Culture
      Change Tool, using 3 different methods of calculating the summary scores. We also
      use a Bayesian hierarchical model to analyze the relationship between a latent
      construct measuring extent of culture change and the composite quality measure.
      RESULTS: Using the original Artifacts scores, the highest performing facility has
      a 2.9 times higher score than the lowest. There is a statistically significant
      relationship between the composite quality measure and each of the 3 summary
      Artifacts scores. Depending on whether original scores, standardized scores, or
      optimal scores are used, a facility at the 10th percentile in terms of culture
      change compared with one at the 90th percentile has 8.0%, 8.9%, or 10.3% more QI
      events. When PCC implementation is considered as a latent construct, 18 low
      performance PCC facilities have, on an average, 16.3% more QI events than 13 high
      performance facilities. CONCLUSIONS: Our results indicate that culture change to
      a PCC model is associated with higher Minimum Data Set-based quality.
      Longitudinal data are needed to better assess whether there is a causal
      relationship between the extent of culture change and quality.

PMID- 23132199
TI  - Effects of digital mammography uptake on downstream breast-related care among
      older women.
AB  - BACKGROUND: Digital mammography is the dominant modality for breast cancer
      screening in the United States. No previous studies have investigated as to how
      introducing digital mammography affects downstream breast-related care.
      OBJECTIVE: Compare breast-related health care use after a screening mammogram
      before and after introduction of digital mammography. RESEARCH DESIGN AND
      SUBJECTS: Longitudinal study of screening mammograms from 14 radiology facilities
      contributing data to the Breast Cancer Surveillance Consortium performed 1 year
      before and 4 years after each facility introduced digital mammography, along with
      linked Medicare claims. We included 30,211 mammograms for women aged 66 years and
      older without breast cancer. MEASURES: Rates of false-positive recall and short
      interval follow-up were based on radiologists' assessments and recommendations;
      rates of follow-up mammography, ultrasound, and breast biopsy use were based on
      Medicare claims. RESULTS: False-positive recall rates increased after the
      introduction of digital mammography. Follow-up mammography use was significantly
      higher across all 4 years after a facility began using digital mammography
      compared with the year before [year 1 odds ratio (OR) = 1.7, 95% confidence
      interval (CI), 1.4-2.1]. Among women with false-positive mammography results, use
      of ultrasound decreased significantly in the second through fourth years after
      digital mammography began (year 2 OR = 0.4, 95% CI, 0.3-0.6). CONCLUSIONS:
      Introduction of a new technology led to changes in health care use that persisted
      for at least 4 years. Comparative effectiveness research on new technologies
      should consider not only diagnostic performance but also downstream utilization
      attributable to this apparent learning curve.

PMID- 23132201
TI  - Physician communication behaviors and trust among black and white patients with
      hypertension.
AB  - BACKGROUND: Racial differences in patient trust have been observed, but it is
      unclear which physician communication behaviors are related to trust, and whether
      the relationship of communication and trust differs among black and white
      patients. OBJECTIVE: We sought to determine whether there were associations
      between physician communication behaviors, visit process measures, and patient
      trust, particularly within racial groups. METHODS: Study participants included 39
      primary care physicians and 227 black and white hypertensive patients from
      community-based practices in Baltimore, MD. Physician informational and affective
      communication behaviors and visit process measures were coded from visit
      audiotapes using the Roter Interaction Analysis System. Patient trust was
      measured using items from the Trust in Physician Scale, and dichotomized
      (high/low). Logistic regression analysis using generalized estimating equations
      was used to assess the association of each physician communication behavior and
      visit process measure with patient trust, among the entire sample and then
      stratified by patient race. RESULTS: Positive physician affect and longer visits
      were significantly associated with high patient trust in unadjusted analyses.
      After adjustment for covariates, positive physician affect remained a significant
      predictor of high patient trust in the overall sample (odds ratio 1.26; 95%
      confidence interval, 1.08, 1.48; P=0.004) and after stratification by race, among
      black patients (odds ratio 1.35; 95% confidence interval, 1.09, 1.67; P=0.006).
      CONCLUSIONS: Physician communication behaviors may have a varying effect on
      patient trust, depending on patient race. Communication skills training programs
      targeting emotion-handling and rapport-building behaviors are promising
      strategies to reduce disparities in health care and to enhance trust among ethnic
      minority patients.

PMID- 23132203
TI  - Better interprofessional teamwork, higher level of organized care, and lower risk
      of burnout in acute health care teams using care pathways: a cluster randomized
      controlled trial.
AB  - BACKGROUND: Effective interprofessional teamwork is an essential component for
      the delivery of high-quality patient care in an increasingly complex medical
      environment. The objective is to evaluate whether the implementation of care
      pathways (CPs) improves teamwork in an acute hospital setting. DESIGN AND
      MEASURES: A posttest-only cluster randomized controlled trial was performed in
      Belgian acute hospitals. Teams caring for patients hospitalized with a proximal
      femur fracture and those hospitalized with an exacerbation of chronic obstructive
      pulmonary disease, were randomized into intervention and control groups. The
      intervention group implemented a CP. The control group provided usual care. A set
      of team input, process, and output indicators were used as effect measures. To
      analyze the results, we performed multilevel statistical analysis. RESULTS:
      Thirty teams and a total of 581 individual team members participated. The
      intervention teams scored significantly better in conflict management [beta=0.30
      (0.11); 95% confidence interval (CI), 0.08 to 0.53]; team climate for innovation
      [beta=0.29 (0.10); 95% CI, 0.09 to 0.49]; and level of organized care [beta=5.56
      (2.05); 95% CI, 1.35 to 9.76]. They also showed lower risk of burnout as they
      scored significantly lower in emotional exhaustion [beta=-0.57 (0.21); 95% CI, 
      1.00 to -0.14] and higher in the level of competence (beta=0.39; 95% CI, 0.15 to
      0.64). No significant effect was found on relational coordination. CONCLUSIONS:
      CPs are effective interventions for improving teamwork, increasing the
      organizational level of care processes, and decreasing risk of burnout for health
      care teams in an acute hospital setting. Through this, high-performance teams can
      be built.

PMID- 23132202
TI  - Organizational culture: an important context for addressing and improving
      hospital to community patient discharge.
AB  - BACKGROUND: Organizational culture is seen as having a growing impact on quality
      and safety of health care, but its impact on hospital to community patient
      discharge is relatively unknown. OBJECTIVES: To explore aspects of organizational
      culture to develop a deeper understanding of the discharge process. RESEARCH
      DESIGN: A qualitative study of stakeholders in the discharge process. Grounded
      Theory was used to analyze the data. SUBJECTS: In 5 European Union countries, 192
      individual and 25 focus group interviews were conducted with patients and
      relatives, hospital physicians, hospital nurses, general practitioners, and
      community nurses. RESULTS: Three themes emerged representing aspects of
      organizational culture: a fragmented hospital to primary care interface,
      undervaluing administrative tasks relative to clinical tasks in the discharge
      process, and lack of reflection on the discharge process or process improvement.
      Nine categories were identified: inward focus of hospital care providers, lack of
      awareness to needs, skills, and work patterns of the professional counterpart,
      lack of a collaborative attitude, relationship between hospital and primary care
      providers, providing care in a "here and now" situation, administrative work
      considered to be burdensome, negative attitude toward feedback, handovers at
      discharge ruled by habits, and appreciating and integrating new practices.
      CONCLUSIONS: On the basis of the data, we hypothesize that the extent to which
      hospital care providers value handovers and the outreach to community care
      providers is critical to effective hospital discharge. Community care providers
      often are insufficiently informed about patient outcomes. Ongoing challenges with
      patient discharge often remain unspoken with opportunities for improvement
      overlooked. Interventions that address organizational culture as a key factor in
      discharge improvement efforts are needed.

PMID- 23132204
TI  - Molecular diversity of Rice grassy stunt virus in Vietnam.
AB  - Rice grassy stunt virus (RGSV, Tenuivirus) recently emerged on rice in Vietnam,
      causing high yield losses during 2006-2009. The genetic diversity of RGSV is
      poorly documented. In this study, the two genes encoded by each ambisense segment
      RNA3 and RNA5 of RGSV isolates from six provinces of South Vietnam were
      sequenced. P3 and Pc3 (RNA3) have unknown function, P5 (RNA5) encodes the
      putative silencing suppressor, and Pc5 (RNA5) encodes the nucleocapsid protein
      (N). The sequences of 17 Vietnamese isolates were compared with reference
      isolates from North and South Philippines. The average nucleotide diversity among
      the isolates was low. We confirmed a higher variability of RNA3 than RNA5 and Pc3
      than P3. No relationships between the genetic diversity and the geographic
      distribution of RGSV isolates could be ascertained, likely because of the long
      distance migration of the insect vector. This data will contribute to a better
      understanding on the RGSV epidemiology in South Vietnam, a prerequisite for
      further management of the disease and rice breeding for resistance.

PMID- 23132205
TI  - Role of AKT isotypes in breast cancer.

PMID- 23132206
TI  - Changing trends in radiation therapy technologies in the last year of life for
      patients diagnosed with metastatic cancer in the United States.
AB  - BACKGROUND: Our goal was to investigate utilization trends for advanced radiation
      therapy (RT) technologies, such as intensity-modulated radiation therapy (IMRT)
      and stereotactic radiosurgery (SRS), in the last year of life among patients
      diagnosed with metastatic cancer. METHODS: We used the Surveillance, Epidemiology
      and End Results (SEER)-Medicare linked databases to analyze claims data in the
      last 12 months of life for 64,525 patients diagnosed with metastatic breast,
      colorectal, lung, pancreas, and prostate cancers from 2000 to 2007. Logistic
      regression modeling was conducted to analyze potential demographic, health
      services, and treatment-related variables' influences on receipt of advanced RT.
      RESULTS: Among the 19,161 (29.7%) patients who received radiation therapy, there
      was a significant decrease in the proportion of patients who received the
      simplest radiation technique (ie, 2D-radiation therapy) (P < .0001), and
      significant increases in the proportions of patients receiving more advanced
      radiation techniques (ie, IMRT, and SRS; P < .0001 for all curves); although the
      rates for use of IMRT and SRS in 2007 remained under 5%. On multivariate
      analyses, receipt of RT varied significantly by non-clinical characteristics such
      as race, marital status, neighborhood income, and SEER region. Patients who
      received hospice care in the last year of life were more likely to receive
      radiation therapy (OR = 1.35, 95% CI = 1.30-1.40) but less likely to be treated
      with IMRT (OR = 0.76, 95% CI = 0.62-0.92). CONCLUSIONS: Although the proportion
      of patients receiving RT in the last year of life for metastatic cancer did not
      change for most of the past decade, we observed significant trends toward more
      advanced radiation techniques.

PMID- 23132207
TI  - Adverse events after recombinant human BMP2 in nonspinal orthopaedic procedures.
AB  - BACKGROUND: The FDA has approved recombinant human bone morphogenetic protein 2
      (rhBMP-2) for treating acute, open tibial shaft fractures. However, the nature
      and frequency of complications after the use of rhBMP-2 in nonspinal orthopaedic
      surgery have not been well characterized. QUESTIONS/PURPOSES: To determine what
      types of adverse events have been reported after the use of rhBMP-2, whether they
      were severe enough to require additional surgery, and after what types of
      operations these adverse events occurred. METHODS: Adverse events reported to the
      FDA's Manufacturer and User Facility Device Experience database were reviewed and
      summarized. RESULTS: Through December 31, 2011, the FDA has received 62 reports
      of adverse events involving rhBMP-2 in nonspinal orthopaedic procedures. Surgical
      site infections and other wound complications, heterotopic bone, pseudarthrosis,
      and local inflammation were among the most commonly reported adverse events.
      Almost half of the reports (30 reports; 48%) stated that the patients required
      secondary interventions to address the reported adverse events. The majority (49
      reports; 79%) described adverse events occurring after unapproved uses, such as
      management of tibial plateau fractures, treatment of congenital pseudarthrosis of
      the tibia, and humeral reconstruction. CONCLUSIONS: Serious adverse events can
      occur after the use of rhBMP-2 in nonspinal orthopaedic procedures and may
      necessitate additional surgery. Most events in this analysis occurred after off
      label uses. Postmarketing review of adverse event reports remains an important
      approach for identifying potential safety concerns.

PMID- 23132208
TI  - Relationships between dimensions of disability experienced by adults living with
      HIV: a structural equation model analysis.
AB  - As individuals age with HIV it is increasingly important to consider the health
      related consequences of HIV and multiple morbidities, known as disability. We
      assessed relationships between four dimensions of disability among adults living
      with HIV. We conducted a structural equation modeling analysis using data from
      913 participants in the Ontario HIV Treatment Network Cohort Study to determine
      relationships between four latent variables of disability in the Episodic
      Disability Framework: physical symptoms and impairments, mental health symptoms
      and impairments, difficulties with day-to-day activities, and challenges to
      social inclusion. Results indicated that physical symptoms and impairments,
      mental health symptoms and impairments and difficulties with day-to-day
      activities directly or indirectly predicted challenges to social inclusion for
      adults living with HIV. Challenges to social inclusion were directly predicted by
      mental health symptoms and indirectly by physical health symptoms via (mediated
      by) having difficulties carrying out day-to-day activities and mental health
      symptoms and impairments. These findings provide a basis for conceptualizing
      disability experienced by people living with HIV. 

PMID- 23132209
TI  - A multimodal optical and electrochemical device for monitoring surface reactions:
      redox active surfaces in porous silicon Rugate filters.
AB  - Herein, mesoporous silicon (PSi) is configured as a single sensing device that
      has dual readouts; as a photonic crystal sensor in a Rugate filter configuration,
      and as a high surface area porous electrode. The as-prepared PSi is chemically
      modified to provide it with stability in aqueous media and to allow for the
      subsequent coupling of chemical species, such as via Cu(I)-catalyzed
      cycloaddition reactions between 1-alkynes and azides ("click" reactions). The
      utility of the bimodal capabilities of the PSi sensor for monitoring surface
      coupling procedures is demonstrated by the covalent coupling of a ferrocene
      derivative, as well as by demonstrating ligand-exchange reactions (LER) at the
      PSi surface. Both types of reactions were monitored through optical reflectivity
      measurements, as well as electrochemically via the oxidation/reduction of the
      surface tethered redox species.

PMID- 23132210
TI  - Nod-like receptors in intestinal host defense:  controlling pathogens, the
      microbiota, or both?
AB  - PURPOSE OF REVIEW: Nod-like receptors (NLRs) are intracellular innate immune
      sensors of microbes and danger signals that control multiple aspects of
      inflammatory responses. We review the evidence that highlights the critical
      importance of NLRs in the host response to intestinal pathogens. Moreover, we
      discuss the potential roles played by NLRs in the dynamic control of the
      intestinal microbiota and how commensal microorganisms may affect host
      susceptibility to enteric bacterial pathogens through interactions with NLRs as
      well as with invading pathogens. RECENT FINDINGS: Recent studies targeting the
      intestinal microbiota in the context of NLR deficiencies suggest inherent
      alterations in bacterial density or abundance may underlie the development of
      inflammatory diseases. As commensal microorganisms may also affect host
      susceptibility to enteric bacterial pathogens, NLRs might promote intestinal
      innate immune defense through mechanisms more complex than previously
      anticipated. SUMMARY: The inclusion of the intestinal microbiota as a critical
      parameter in innate immunity represents an exciting new dimension for
      understanding NLR functioning and the clinical implications for human health.

PMID- 23132212
TI  - Aspects of large intestinal health and disease.

PMID- 23132213
TI  - Polypoidal choroidal vasculopathy in a case with retinitis pigmentosa.
AB  - There have been no reports describing polypoidal choroidal vasculopathy (PCV) in
      eyes with retinitis pigmentosa (RP). A 63-year-old woman who had been diagnosed
      as having RP was referred to us because of sudden onset of blurred vision in her
      right eye. Funduscopic examination revealed retinal findings typical of RP in
      both eyes. The macular area of the right fundus showed polypoidal lesions with
      massive hemorrhages. Fluorescein angiography and indocyanine green angiography
      showed multiple polypoidal lesions. Optical coherence tomography showed a large
      hemorrhagic retinal pigment epithelial (RPE) detachment and polypoidal lesions.
      The PCV subsided after three applications of anti-vascular endothelial growth
      factor (VEGF) therapy and a single application of photodynamic therapy, but
      "mottled lesions" with hyper- and hypofluorescence appeared temporal to the
      macula after disappearance of hemorrhage. We present a case of PCV in an eye with
      RP. Further studies are necessary to clarify whether anti-VEGF therapies could
      affect RPE status in eyes with RP.

PMID- 23132211
TI  - Eosinophils in infection and intestinal immunity.
AB  - PURPOSE OF REVIEW: Inflammatory bowel diseases (IBDs, e.g., Crohn's disease and
      ulcerative colitis) are thought to be a consequence of an uncontrolled
      inflammatory response against luminal antigens, including commensal bacteria. The
      observed link between eosinophil levels and severity and remission rates in IBD
      has led to speculation that eosinophils may contribute to the antimicrobial
      inflammatory response in IBD. RECENT FINDINGS: Eosinophils express the necessary
      cellular machinery (innate immune receptors, proinflammatory cytokines,
      antibacterial proteins, and DNA traps) to mount an efficient antibacterial
      response; however, the rapid decline in eosinophil numbers following acute
      systemic bacterial infection suggests a very limited role for eosinophils in
      bacterial responses. SUMMARY: We describe the clinical evidence of eosinophil
      involvement in IBD, summarize the in-vitro and in-vivo evidence of eosinophil
      antibacterial activity and the biology of eosinophils focusing on eosinophil
      mediated bactericidal mechanisms and the involvement of eosinophil-derived
      granule proteins in this response, and conceptualize the contribution of
      eosinophils to a response against commensal bacteria in IBD.

PMID- 23132215
TI  - The first case of Candida dubliniensis endophthalmitis in North America.

PMID- 23132214
TI  - Hypothalamic-pituitary-adrenal axis function following intravitreal triamcinolone
      acetonide injection.
AB  - To evaluate the pituitary-adrenal axis function by means of the
      adrenocorticotropic hormone (ACTH) stimulation test following a single
      intravitreal injection of triamcinolone acetonide (IVTA). Prospective comparative
      clinical interventional study. Twenty-eight patients (28 eyes) received a single
      IVTA (4 mg in 0.1 ml) for macular edema. The basal cortisol level and the
      response to 1 MUg adrenocorticotropic hormone stimulation were determined on the
      morning before IVTA injection and at 1 day and 1, 2, and 4 weeks after IVTA
      injection. Results were compared with those obtained from a control group of 50
      healthy subjects. All patients in the study had normal basal cortisol and normal
      response to ACTH challenge before receiving IVTA. 1 day following IVTA, basal
      cortisol was suppressed in one patient in the study group. Fasting serum cortisol
      levels at 1, 2, and 4 weeks after IVTA injection were normal in all patients in
      the study group. 1 day following IVTA, the peak response to ACTH at 30 min was
      blunted in four patients (14.3 % of the study group, p = 0.05) and the cortisol
      response at 60 min was suppressed (p = 0.009). 1 week following IVTA, the
      response to ACTH challenge was blunted in only one patient. A single IVTA
      injection may be associated with impaired hypothalamic-pituitary-adrenal function
      in some patients during the first 24 h following IVTA.

PMID- 23132216
TI  - [Survey medical intensive care: structure of in-patient care and supply of
      services in medical intensive care].

PMID- 23132217
TI  - [Medical intensive care: new career prospects in internal medicine].

PMID- 23132218
TI  - Site-selective sequential coupling reactions controlled by "Electrochemical
      Reaction Site Switching": a straightforward approach to 1,4-bis(diaryl)buta-1,3
      diynes.
AB  - Site-selective sequential coupling reactions directed toward
      bis(diaryl)butadiynes are described. The reaction site could be controlled
      completely by the on/off application of electricity. The electro-oxidative homo
      coupling of terminal alkynes (electricity ON) and the subsequent Suzuki-Miyaura
      coupling (electricity OFF) afforded bis(diaryl)butadiynes in high yields. The
      obtained 1,4-bis(diaryl)butadiynes could be converted to a 2,5
      bis(diaryl)thiophene derivative, which exhibited blue fluorescence.

PMID- 23132219
TI  - Graphene is not alone.

PMID- 23132222
TI  - Atomic force microscopy: A tip for diagnosing cancer.

PMID- 23132220
TI  - Microscopic reversibility as the organizing principle of molecular machines.

PMID- 23132223
TI  - Graphene: Conductivity measurements pick up.

PMID- 23132224
TI  - Spintronics: News from the organic arena.

PMID- 23132227
TI  - Double trigonal warping and the anomalous quantum Hall step in bilayer graphene
      with Rashba spin-orbit coupling.
AB  - We demonstrate that the trigonal warping observed in bilayer graphene is doubled
      in the presence of Rashba spin-orbit (RSO) coupling, i.e. the Dirac points along
      the three-fold symmetry axis are doubled. There are now seven Dirac points.
      Furthermore, the RSO interaction breaks the electron-hole symmetry of the
      magnetic band structure. The most intriguing feature is that the step of the
      quantum Hall plateau at zero energy is four times that at finite energy. The
      number of Dirac points and the zero energy Hall step are only determined by the
      existence of RSO coupling, but are independent of the strength of the coupling.
      The robustness of these phenomena suggests equivalence between the RSO coupling
      and the topological effect in bilayer coupling.

PMID- 23132228
TI  - Development of silica-coated silver iodide nanoparticles and their
      biodistribution.
AB  - Nanomaterials have great potential in the field of medicine and have been studied
      extensively.  In a previous study, we addressed the potential of silver iodide
      (AgI) as X-ray contrast media, because it possessed high imaging ability in the
      measurement by X-ray computed tomography (X-CT) in vitro, and its surface can be
      modified with many functional groups.  We developed the method of silica coating
      to make AgI nanoparticles more stable and uniform in size.  However, the safety
      and metabolism of nanoparticles in vivo remains to be determined.  The objective
      of the present study was to evaluate the in vivo biodistribution of silica-coated
      AgI nanoparticles (SAgINPs).  X-CT, transmission electron microscopy (TEM), and
      inductively coupled plasma atomic emission spectrometry (ICP-AES) were performed
      prior to and at intervals following the intravenous administration of SAgINPs to
      rats and rabbits.  ICP-AES is a spectral technique that can determine the
      presence and concentrations of metal samples.  The X-CT study showed long-period
      enhancement in the liver and spleen, but not in the bladder of rats.  The TEM
      study demonstrated that SAgINPs were found in hepatocytes.  Using ICP-AES, Ag was
      detected in the bile juice of rabbits, but not found in the urine of these
      animals, suggesting that SAgINPs are excreted via the liver.  This study shows
      the quantitative biodistribution of silica-coated nanoparticles for the first
      time, indicating that our silica coating technique is useful for development of
      nanoparticles with hepatic excretion.  In conclusion, the SAgINPs may provide X
      ray contrast media with high imaging ability and biocompatibility.

PMID- 23132225
TI  - Electronics and optoelectronics of two-dimensional transition metal
      dichalcogenides.
AB  - The remarkable properties of graphene have renewed interest in inorganic, two
      dimensional materials with unique electronic and optical attributes. Transition
      metal dichalcogenides (TMDCs) are layered materials with strong in-plane bonding
      and weak out-of-plane interactions enabling exfoliation into two-dimensional
      layers of single unit cell thickness. Although TMDCs have been studied for
      decades, recent advances in nanoscale materials characterization and device
      fabrication have opened up new opportunities for two-dimensional layers of thin
      TMDCs in nanoelectronics and optoelectronics. TMDCs such as MoS(2), MoSe(2),
      WS(2) and WSe(2) have sizable bandgaps that change from indirect to direct in
      single layers, allowing applications such as transistors, photodetectors and
      electroluminescent devices. We review the historical development of TMDCs,
      methods for preparing atomically thin layers, their electronic and optical
      properties, and prospects for future advances in electronics and optoelectronics.

PMID- 23132229
TI  - Psoriasis is associated with low serum levels of hydrogen sulfide, a potential
      anti-inflammatory molecule.
AB  - Psoriasis, characterized by circumscribed, red, thickened plaques with an
      overlying silver-white scale, is a common T-cell-mediated chronic inflammatory
      skin disease.  Although hydrogen sulfide (H(2)S) has been shown to be a signaling
      molecule with both pro- or anti-inflammatory effects, its relationship with
      psoriasis has not been elucidated.  In the present study, 15 patients with
      chronic progressive psoriasis and 15 healthy volunteers were investigated.  Serum
      H(2)S levels in psoriasis patients were significantly lower than those of healthy
      controls (16.69 +/- 5.47 MUM vs. 34.5 +/- 6.39 MUM).  In contrast, serum levels
      of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin
      8 (IL-8) were significantly higher in psoriasis patients than healthy controls
      (22.88 +/- 6.24 pg/ml vs. 12.07 +/- 3.68 pg/ml; 61.47 +/- 8.21 pg/ml vs.  31.54
      +/- 13.73 pg/ml; and 39.43 +/- 8.56 pg/ml vs. 20.55 +/- 6.45 pg/ml,
      respectively).  The serum H(2)S levels negatively correlated with clinical
      disease severity.  Furthermore, treatment of HaCaT human keratinocytes with TNF
      alpha increased the levels of nitric oxide (NO), IL-6 and IL-8 (32.21 +/- 5.71
      MUM vs. 3.22 +/- 0.98 MUM; 203.96 +/- 13.16 pg/ml vs. 13.57 +/- 3.75 pg/ml; and
      301.24 +/- 30.17 pg/ml vs. 29.06 +/- 10.91 pg/ml, respectively) in the culture
      media.  Exogenous H(2)S inhibited the TNF-alpha-mediated upregulation of NO, IL-6
      and IL-8 in a dose-dependent manner.  In addition, H(2)S inhibited TNF-alpha
      mediated activation of p38, extracellular-signal-regulated kinase and nuclear
      factor kappa B.  In conclusion, H(2)S may play a protective role in the
      pathogenesis of psoriasis.  H(2)S-releasing agents may be promising therapeutics
      for psoriasis.

PMID- 23132230
TI  - Synthesis of monodispersed magnetite nanoparticles from iron pivalate clusters.
AB  - The iron pivalate clusters
      [Fe(3)O(O(2)C(t)Bu)(6)(H(2)O)(3)](O(2)C(t)Bu).HO(2)C(t)Bu (1),
      [Fe(8)(OH)(4)(O(2)C(t)Bu)(12)(OC(6)H(4)C(6)H(5))(8)] (2) and
      [Fe(3)O(O(2)C(t)Bu)(6)(C(5)H(5)N)(3)] (3) have been used as single source
      precursors to synthesise iron oxide nanoparticles by a hot injection thermal
      decomposition method in oleylamine, hexadecanol, oleic acid, oleylamine/oleic
      acid with dodecanol or octyl ether as solvent. The effect of the different
      reaction parameters such as temperature, reaction time and capping agents on the
      phase and morphology were studied. The reaction time was studied for (1) by
      thermolysis in a mixture of oleylamine, oleic acid, hexadecanol and dodecanol
      (solvent) at 260  degrees C. The results obtained showed that a mixture of
      maghemite-C (Fe(2)O(3)) and magnetite (Fe(3)O(4)) were obtained for aliquots
      withdrawn for reaction times of less than 30 minutes whilst only magnetite was
      obtained after one hour. The nanoparticles were characterised by p-XRD, TEM and
      magnetic measurements. TEM showed that monodispersed magnetite particles were
      obtained when the precursor was injected at the boiling point of the solvent. The
      diameter of the monodispersed nanoparticles obtained by the thermolysis of
      [Fe(3)O(O(2)C(t)Bu)(6)(H(2)O)(3)](O(2)C(t)Bu).HO(2)C(t)Bu (1) in oleylamine,
      hexadecanol, oleic acid with dodecanol or octyl ether as solvent were 4.3 +/- 0.4
      and 4.9 +/- 0.5 nm respectively. Magnetic measurements revealed that all the
      particles are superparamagnetic.

PMID- 23132231
TI  - "5 mins of uncomfyness is better than dealing with cancer 4 a lifetime": an
      exploratory qualitative analysis of cervical and breast cancer screening dialogue
      on Twitter.
AB  - Twitter.com is a "micro-blogging" website. Although Twitter use is growing
      rapidly, little is known about health behavior discussions on this site, even
      though a majority of messages are publicly available. We retrieved publicly
      available Twitter messages during a 5-week period in early 2012, searching
      separately for the terms "Pap smear" and "mammogram." We used content analysis to
      code each 140-character message, generating a separate coding framework for each
      cancer screening term and calculating the frequencies of comments. Using the
      brief account description, we also coded the author as individual, organization,
      or news media outlet. There were 203 Pap smear and 271 mammogram messages coded,
      over three fourths of which were from individual accounts. Overall, 22 % of Pap
      smear messages and 25 % of mammogram messages discussed personal experiences,
      including attending appointments, negative sentiment about the procedure, and
      results. Other messages from both individuals and organizations (8 % Pap smear,
      18 % mammogram) promoted screening. About one quarter of the messages expressed
      personal experiences with cancer screening. This demonstrates that Twitter can be
      a rich source of information and could be used to design new health-related
      interventions.

PMID- 23132232
TI  - Renal denervation for treatment-resistant hypertension.
AB  - Hypertension is a major public health concern that is increasing in prevalence.
      Lifestyle and pharmacological management are not always sufficient to control
      blood pressure and treatment-resistant hypertension is a recognized clinical
      challenge. Renal sympathetic denervation (RSD) represents a new frontier in the
      treatment of resistant hypertension. RESULTS: from the Symplicity HTN-1 and HTN-2
      trials have demonstrated evidence that suggests RSD can safely reduce blood
      pressure in patients with this condition. More research is needed to verify these
      data, clarify unanswered questions and assess future applications of RSD. This
      review provides a detailed overview on the history of hypertension, treatment
      resistant hypertension, the rationale behind RSD, current evidence and potential
      future applications of RSD. An overview of current and upcoming RSD devices is
      also included.

PMID- 23132233
TI  - Reminiscence and a very warm welcome to the new editor-in-chief.

PMID- 23132234
TI  - Theoretical study of the Si(5-n)(BH)n2- and Na(Si(5-n)(BH)n)- (n = 0-5) systems.
AB  - The potential energy surfaces of the Na(Si(5-n)(BH)(n))(-) and Si(5-n)(BH)(n)(2-)
      (n = 0-5) systems have been explored in detail. We established that all the
      global minimum structures of anionic and dianionic systems can be obtained by
      substitution of one or more silicon atoms of the global minima of NaSi(5)(-) and
      Si(5)(2-) for B-H units. The conservation of the overall structure upon
      isoelectronic substitution was shown to be due to the preservation of the
      chemical bonding pattern. Theoretical VDEs were calculated for all of the
      sodiated Na(Si(5-n)(BH)(n))(-) (n = 0-5) systems to facilitate their experimental
      detection.

PMID- 23132235
TI  - Classic lobular carcinoma in situ and atypical lobular hyperplasia at
      percutaneous breast core biopsy: outcomes of prospective excision.
AB  - BACKGROUND: No consensus exists on the need to excise breast lesions that yield
      classic lobular carcinoma in situ (LCIS) or atypical lobular hyperplasia (ALH)
      (known together as classic lobular neoplasia [LN]) as the highest risk lesion at
      percutaneous core-needle biopsy (CNB). Here, the authors report findings from 72
      consecutive lesions with LN at CNB and prospective surgical excision (EXB).
      METHODS: Lesions that yielded LN at CNB at the authors' center have been referred
      for EXB since June 2004, regardless of imaging-histologic concordance. A lesion
      was "concordant" if histologic findings provided sufficient explanation for
      imaging. An upgrade consisted of ductal carcinoma in situ and/or invasive
      carcinoma at EXB. Statistical analysis, including 95% confidence intervals (CIs),
      was performed. RESULTS: Between June 2004 and May 2009, CNB of 85 consecutive
      lesions yielded LN without other high-risk histologies. Eighty of 85 lesions
      (94%) underwent prospective EXB. Seventy-two of 85 lesions (90%; 42 LCIS, 30 ALH)
      had concordant imaging-histologic findings. EXB yielded low-grade carcinoma in 2
      of 72 cases (3%; 95% CI, 0%-9%). In both patients, stereotactic, 11-gauge, vacuum
      assisted biopsy of calcifications yielded calcifications in benign parenchyma and
      ALH. CNB results were discordant in 8 of 80 lesions (10%; 4 LCIS, 4 ALH), and EXB
      yielded cancer in 3 of those 8 lesions (38%; 95% CI, 9%-76%). The upgrade rate
      was significantly higher for discordant lesions versus concordant lesions (38% vs
      3%; P < .01). CONCLUSIONS: Prospective excision of LN identified carcinoma in 3%
      (95% CI, 0%-9%) of concordant cases versus 38% (95% CI, 9%-76%) of discordant
      cases. The current data provide an unbiased assessment of the upgrade rate of LN
      diagnosed at CNB.

PMID- 23132236
TI  - Duodenum between the aorta and the SMA does not exclude malrotation.

PMID- 23132238
TI  - Vulnerable groups mustn't become guinea pigs.

PMID- 23132239
TI  - Piecing together the vertebrate skull.
AB  - In a 1993 Development paper, the quail-chick chimera system was applied to
      decipher the embryonic origin of the bones of the head skeleton of the avian
      embryo. The data reported in this article, together with those from previous
      works, allowed us to assign a precise embryonic origin to all the bones forming
      the avian skull. It turned out that their major source is the neural crest, with
      additional contributions from the head paraxial mesoderm and the first five
      somites, laying to rest a long-standing debate about the origin of the skull.

PMID- 23132237
TI  - Percutaneous transluminal pulmonary angioplasty for the treatment of chronic
      thromboembolic pulmonary hypertension.
AB  - BACKGROUND: Chronic thromboembolic pulmonary hypertension leads to pulmonary
      hypertension and right-sided heart failure. The purpose of this study was to
      investigate the efficacy of percutaneous transluminal pulmonary angioplasty
      (PTPA) for the treatment of chronic thromboembolic pulmonary hypertension.
      METHODS AND RESULTS: Twenty-nine patients with chronic thromboembolic pulmonary
      hypertension underwent PTPA. One patient had a wiring perforation as a
      complication of PTPA and died 2 days after the procedure. In the remaining 28
      patients, PTPA did not produce immediate hemodynamic improvement at the time of
      the procedure. However, after follow-up (6.0 +/- 6.9 months), New York Heart
      Association functional classifications and levels of plasma B-type natriuretic
      peptide significantly improved (both P<0.01). Hemodynamic parameters also
      significantly improved (mean pulmonary arterial pressure, 45.3 +/- 9.8 versus
      31.8 +/- 10.0 mm Hg; cardiac output, 3.6 +/- 1.2 versus 4.6 +/- 1.7 L/min,
      baseline versus follow-up, respectively; both P<0.01). Twenty-seven of 51
      procedures in total (53%), and 19 of 28 first procedures (68%), had reperfusion
      pulmonary edema as the chief complication. Patients with severe clinical signs
      and/or severe hemodynamics at baseline had a high risk of reperfusion pulmonary
      edema. CONCLUSIONS: PTPA improved subjective symptoms and objective variables,
      including pulmonary hemodynamics. PTPA may be a promising therapeutic strategy
      for the treatment of chronic thromboembolic pulmonary hypertension. CLINICAL
      TRIAL REGISTRATION: URL: http://www.umin.ac.jp. Unique identifier: UMIN000001572.

PMID- 23132240
TI  - Drosophila neuroblasts: a model for stem cell biology.
AB  - Drosophila neuroblasts, the stem cells of the developing fly brain, have emerged
      as a key model system for neural stem cell biology and have provided key insights
      into the mechanisms underlying asymmetric cell division and tumor formation. More
      recently, they have also been used to understand how neural progenitors can
      generate different neuronal subtypes over time, how their cell cycle entry and
      exit are coordinated with development, and how proliferation in the brain is
      spared from the growth restrictions that occur in other organs upon starvation.
      In this Primer, we describe the biology of Drosophila neuroblasts and highlight
      the most recent advances made using neuroblasts as a model system.

PMID- 23132241
TI  - Endocytic receptor-mediated control of morphogen signaling.
AB  - Receptor-mediated endocytosis provides a mechanism by which cells take up
      signaling molecules from the extracellular space. Recent studies have shown that
      one class of endocytic receptors, the low-density lipoprotein receptor-related
      proteins (LRPs), is of particular relevance for embryonic development. In this
      Primer, we describe how LRPs constitute central pathways that modulate morphogen
      presentation to target tissues and cellular signal reception, and how LRP
      dysfunction leads to developmental disturbances in many species.

PMID- 23132242
TI  - SUMO1-activating enzyme subunit 1 is essential for the survival of hematopoietic
      stem/progenitor cells in zebrafish.
AB  - In vertebrates, establishment of the hematopoietic stem/progenitor cell (HSPC)
      pool involves mobilization of these cells in successive developmental
      hematopoietic niches. In zebrafish, HSPCs originate from the ventral wall of the
      dorsal aorta (VDA), the equivalent of the mammalian aorta-gonad-mesonephros
      (AGM). The HSPCs subsequently migrate to the caudal hematopoietic tissue (CHT)
      for transitory expansion and differentiation during the larval stage, and they
      finally colonize the kidney, where hematopoiesis takes place in adult fish. Here,
      we report the isolation and characterization of a zebrafish mutant, tango(hkz5),
      which shows defects of definitive hematopoiesis. In tango(hkz5) mutants, HSPCs
      initiate normally in the AGM and subsequently colonize the CHT. However,
      definitive hematopoiesis is not sustained in the CHT owing to accelerated
      apoptosis and diminished proliferation of HSPCs. Positional cloning reveals that
      tango(hkz5) encodes SUMO1-activating enzyme subunit 1 (Sae1). A chimera
      generation experiment and biochemistry analysis reveal that sae1 is cell
      autonomously required for definitive hematopoiesis and that the tango(hkz5)
      mutation produces a truncated Sae1 protein (DeltaSae1), resulting in systemic
      reduction of sumoylation. Our findings demonstrate that sae1 is essential for the
      maintenance of HSPCs during fetal hematopoiesis in zebrafish.

PMID- 23132243
TI  - Epigenetic reprogramming in somatic cells induced by extract from germinal
      vesicle stage pig oocytes.
AB  - Genomic reprogramming factors in the cytoplasm of germinal vesicle (GV) stage
      oocytes have been shown to improve the efficiency of producing cloned mouse
      offspring through the exposure of nuclei to a GV cytoplasmic extract prior to
      somatic cell nuclear transfer (SCNT) to enucleated oocytes. Here, we developed an
      extract of GV stage pig oocytes (GVcyto-extract) to investigate epigenetic
      reprogramming events in treated somatic cell nuclei. This extract induced
      differentiation-associated changes in fibroblasts, resulting in cells that
      exhibit pluripotent stem cell-like characteristics and that redifferentiate into
      three primary germ cell layers both in vivo and in vitro. The GVcyto-extract
      treatment induced large numbers of high-quality SCNT-generated blastocysts, with
      methylation and acetylation of H3-K9 and expression of Oct4 and Nanog at levels
      similar to in vitro fertilized embryos. Thus, GVcyto-extract could elicit
      differentiation plasticity in treated fibroblasts, and SCNT-mediated
      reprogramming reset the epigenetic state in treated cells more efficiently than
      in untreated cells. In summary, we provide evidence for the generation of stem
      like cells from differentiated somatic cells by treatment with porcine GVcyto
      extract.

PMID- 23132244
TI  - miR-1 and miR-206 regulate angiogenesis by modulating VegfA expression in
      zebrafish.
AB  - Cellular communication across tissues is an essential process during embryonic
      development. Secreted factors with potent morphogenetic activity are key elements
      of this cross-talk, and precise regulation of their expression is required to
      elicit appropriate physiological responses. MicroRNAs (miRNAs) are versatile post
      transcriptional modulators of gene expression. However, the large number of
      putative targets for each miRNA hinders the identification of physiologically
      relevant miRNA-target interactions. Here we show that miR-1 and miR-206
      negatively regulate angiogenesis during zebrafish development. Using target
      protectors, our results indicate that miR-1/206 directly regulate the levels of
      Vascular endothelial growth factor A (VegfA) in muscle, controlling the strength
      of angiogenic signaling to the endothelium. Conversely, reducing the levels of
      VegfAa, but not VegfAb, rescued the increase in angiogenesis observed when miR
      1/206 were knocked down. These findings uncover a novel function for miR-1/206 in
      the control of developmental angiogenesis through the regulation of VegfA, and
      identify a key role for miRNAs as regulators of cross-tissue signaling.

PMID- 23132245
TI  - Different assemblies of Notch receptors coordinate the distribution of the major
      bronchial Clara, ciliated and neuroendocrine cells.
AB  - In the developing lung, it is thought that the terminal buds of elongating
      airways contain a population of multipotent epithelial progenitors. As the
      bronchial tree extends, descendants of these cells give rise to lineage
      restricted progenitors in the conducting airways via Notch signaling, which is
      involved in the establishment of epithelial Clara, ciliated and pulmonary
      neuroendocrine (NE) cell populations. However, the precise molecular details of
      this selection process are still emerging. Our stepwise removal of the three
      Notch receptors from the developing lung epithelium reveals that, whereas Notch2
      mediates the Clara/ciliated cell fate decision with negligible contributions from
      Notch1 and Notch3, all three Notch receptors contribute in an additive manner to
      regulate the abundance of NE cells and the size of the presumptive pulmonary
      neuroepithelial body (pNEB) as a result of mutual interactions between NE cells
      and the Notch-dependent, SSEA-1(+), CC10(-) cell population surrounding the pNEB
      (SPNC cells). Ectopic expression of the Notch1 or Notch2 intracellular domain was
      sufficient to induce SSEA-1(+) cells and to suppress pNEB formation without
      expending Clara cells. We provide evidence that the additive functions of Notch
      receptors, together with other signaling pathways, maintains the expression of
      Hes1, a key regulator of NE cell fate, and that maintenance of Hes1 expression in
      epithelial cells is key to the regulation of pNEB size. These results suggest
      that two different assemblies of Notch receptors coordinate the numbers and
      distribution of the major epithelial cell types in the conducting airway during
      lung organogenesis.

PMID- 23132246
TI  - A dual function for canonical Wnt/beta-catenin signaling in the developing
      mammalian cochlea.
AB  - The canonical Wnt/beta-catenin signaling pathway is known to play crucial roles
      in organogenesis by regulating both proliferation and differentiation. In the
      inner ear, this pathway has been shown to regulate the size of the otic placode
      from which the cochlea will arise; however, direct activity of canonical Wnt
      signaling as well as its function during cochlear mechanosensory hair cell
      development had yet to be identified. Using TCF/Lef:H2B-GFP reporter mice and
      transfection of an independent TCF/Lef reporter construct, we describe the
      pattern of canonical Wnt activity in the developing mouse cochlea. We show that
      prior to terminal mitosis, canonical Wnt activity is high in early prosensory
      cells from which hair cells and support cells will differentiate, and activity
      becomes reduced as development progresses. Using an in vitro model we demonstrate
      that Wnt/beta-catenin signaling regulates both proliferation and hair cell
      differentiation within the developing cochlear duct. Inhibition of Wnt/beta
      catenin signaling blocks proliferation during early mitotic phases of development
      and inhibits hair cell formation in the differentiating organ of Corti.
      Conversely, activation increases the number of hair cells that differentiate and
      induces proliferation in prosensory cells, causing an expansion of the Sox2
      positive prosensory domain. We further demonstrate that the induced proliferation
      of Sox2-positive cells may be mediated by the cell cycle regulator cyclin D1.
      Lastly, we provide evidence that the mitotic Sox2-positive cells are competent to
      differentiate into hair cells. Combined, our data suggest that Wnt/beta-catenin
      signaling has a dual function in cochlear development, regulating both
      proliferation and hair cell differentiation.

PMID- 23132248
TI  - A fast and sensitive alternative for beta-galactosidase detection in mouse
      embryos.
AB  - The bacterial lacZ gene is widely used as a reporter in a myriad of mouse
      transgenic experiments. beta-Galactosidase, encoded by lacZ, is usually detected
      using X-gal in combination with ferric and ferrous ions. This assay produces a
      blue indole precipitate that is easy to detect visually. Here, we show that
      Salmon-gal in combination with tetrazolium salts provides a more sensitive and
      faster staining reaction than the traditional beta-galactosidase assay in mouse
      embryos. Using a combination of Salmon-gal and tetranitroblue tetrazolium, we
      were able to visualize the activity of beta-galactosidase in embryos at stages
      when the customary X-gal reaction failed to detect staining. Our studies provide
      an enhanced alternative for beta-galactosidase detection in expression and cell
      fate studies that use lacZ-based transgenic mouse lines.

PMID- 23132247
TI  - Dishevelled limits Notch signalling through inhibition of CSL.
AB  - Notch and Wnt are highly conserved signalling pathways that are used repeatedly
      throughout animal development to generate a diverse array of cell types. However,
      they often have opposing effects on cell-fate decisions with each pathway
      promoting an alternate outcome. Commonly, a cell receiving both signals exhibits
      only Wnt pathway activity. This suggests that Wnt inhibits Notch activity to
      promote a Wnt-ON/Notch-OFF output; but what might underpin this Notch regulation
      is not understood. Here, we show that Wnt acts via Dishevelled to inhibit Notch
      signalling, and that this crosstalk regulates cell-fate specification in vivo
      during Xenopus development. Mechanistically, Dishevelled binds and directly
      inhibits CSL transcription factors downstream of Notch receptors, reducing their
      activity. Furthermore, our data suggest that this crosstalk mechanism is
      conserved between vertebrate and invertebrate homologues. Thus, we identify a
      dual function for Dishevelled as an inhibitor of Notch signalling and an
      activator of the Wnt pathway that sharpens the distinction between opposing Wnt
      and Notch responses, allowing for robust cell-fate decisions.

PMID- 23132249
TI  - Acute treatment with bis selenide, an organic compound containing the trace
      element selenium, prevents memory deficits induced by reserpine in rats.
AB  - Taking into account the promising pharmacological actions of (Z)-2,3-bis(4
      chlorophenylselanyl) prop-2-en-1-ol) (bis selenide), an organic compound
      containing the trace element selenium, and the constant search for drugs that
      improve the cognitive performance, the objective of the present study was to
      investigate whether bis selenide treatment ameliorates memory deficits induced by
      reserpine in rats. For this aim, male adult rats received a single subcutaneous
      injection of reserpine (1 mg/kg), a biogenic amine-depleting agent used to induce
      memory deficit. After 24 h, bis selenide at doses of 25 and 50 mg/kg was
      administered to rats by intragastric route, and 1 h later, the animals were
      submitted to behavior tasks. The effects of acute administration of bis selenide
      on memory were evaluated by social recognition, step-down passive avoidance, and
      object recognition paradigms. Exploratory and locomotor activities of rats were
      determined using the open-field test. Analysis of data revealed that the social
      memory disruption caused by reserpine was reversed by bis selenide at both doses.
      In addition, bis selenide, at the highest dose, prevented the memory deficit
      resulting from reserpine administration to rats in step-down passive avoidance
      and object recognition tasks. No significant alterations in locomotor and
      exploratory behaviors were found in animals treated with reserpine and/or bis
      selenide. Results obtained from distinct memory behavioral paradigms revealed
      that an acute treatment with bis selenide attenuated memory deficits induced by
      reserpine in rats.

PMID- 23132250
TI  - The effects of magnesium deficiency on molybdenum metabolism in rats.
AB  - Our previous report indicated that magnesium (Mg) deficiency increased molybdenum
      (Mo) concentration in the rat liver, suggesting the possibility that Mg
      deficiency affects Mo metabolism. Growing male rats were given a control diet or
      a Mg-deficient diet for 4 weeks. Urine and feces were collected during the second
      and fourth weeks of the feeding trial. The liver, kidney, spleen, skeletal
      muscle, and blood were collected at the end of the feeding trial. Mg deficiency
      did not affect the apparent absorption of Mo, but it reduced urinary excretion of
      Mo. The retention of Mo tended to be higher in the Mg-deficient group than in the
      control group. Hepatic Mo concentration was higher in the Mg-deficient group than
      in the control group, but Mg deficiency did not affect Mo concentration in other
      tissues and plasma. Mg deficiency downregulated the mRNA expression of Mo
      transporter 2 (MOT2) in the liver, but not in the kidney. These results suggest
      that Mg deficiency decreases urinary Mo excretion, which is too slight to affect
      plasma Mo concentration, and that Mg deficiency selectively disturbs the
      homeostatic mechanism of Mo in the liver, which is not related to the mRNA
      expression of MOT2 in the liver.

PMID- 23132251
TI  - Cross-cultural comparisons:  methodological concerns.

PMID- 23132252
TI  - Optimization of auto-induction medium for G-CSF production by Escherichia coli
      using artificial neural networks coupled with genetic algorithm.
AB  - Granulocyte colony-stimulating factor (G-CSF) is a cytokine widely used in cancer
      patients receiving high doses of chemotherapeutic drugs to prevent the
      chemotherapy-induced suppression of white blood cells. The production of
      recombinant G-CSF should be increased to meet the increasing market demand. This
      study aims to model and optimize the carbon source of auto-induction medium to
      enhance G-CSF production using artificial neural networks coupled with genetic
      algorithm. In this approach, artificial neural networks served as bioprocess
      modeling tools, and genetic algorithm (GA) was applied to optimize the
      established artificial neural network models. Two artificial neural network
      models were constructed: the back-propagation (BP) network and the radial basis
      function (RBF) network. The root mean square error, coefficient of determination,
      and standard error of prediction of the BP model were 0.0375, 0.959, and 8.49 %,
      respectively, whereas those of the RBF model were 0.0257, 0.980, and 5.82 %,
      respectively. These values indicated that the RBF model possessed higher fitness
      and prediction accuracy than the BP model. Under the optimized auto-induction
      medium, the predicted maximum G-CSF yield by the BP-GA approach was 71.66 %,
      whereas that by the RBF-GA approach was 75.17 %. These predicted values are in
      agreement with the experimental results, with 72.4 and 76.014 % for the BP-GA and
      RBF-GA models, respectively. These results suggest that RBF-GA is superior to BP
      GA. The developed approach in this study may be helpful in modeling and
      optimizing other multivariable, non-linear, and time-variant bioprocesses.

PMID- 23132253
TI  - Profile and multidrug resistance determinants of Chryseobacterium indologenes
      from seawater and marine fauna.
AB  - The aim of this study was to investigate the prevalence and genetic basis of
      multidrug resistance in Chryseobacterium indologenes from seawater and marine
      invertebrates used for human consumption, in Kastela Bay, Adriatic Sea, Croatia.
      Out of 16 samples of seawater, Mediterranean mussel (Mytilus galloprovincialis
      Lam.), Rayed Mediterranean limpets (Patella caerulea L.) and Purple sea urchins
      (Paracentrotus lividus Lam.) collected, 15 were positive for C. indologenes. In
      total, 41 isolates were randomly selected and tested for antibiotic
      susceptibility by disc-diffusion and broth microdilution methods. PCR was used to
      detect alleles encoding extended-spectrum (ESBLs) and metallo-beta-lactamases
      (MBLs). The clonality of beta-lactamase-producing strains was evaluated by random
      amplified polymorphic DNA (RAPD) analysis. All C. indologenes isolates showed
      multiple resistance to at least 9 out of 16 antibiotics tested. Lowest resistance
      rates were found for piperacillin (9.7 %) and ciprofloxacin (24.4 %), whereas
      only piperacillin/tazobactam and trimethoprim/sulfamethoxazole showed 100 %
      activity. More than half of isolates carried bla (IND)-type gene, including 2
      isolates carrying bla (IND-2) and 21 carrying bla (IND-7), that was identified as
      a major MBL genotype in isolates from Adriatic Sea. RAPD typing of IND-producing
      isolates revealed 6 major groups with no predominant clone in population. The
      presence of multidrug resistant and IND-producing C. indologenes in marine
      environment, including marine fauna, pose a risk for transmitting this
      opportunistic pathogen to humans through recreation or consummation of seafood.
      In addition, the antibiotic susceptibility test results have practical relevance
      for empirical treatment of C. indologenes infections.

PMID- 23132254
TI  - Optimization of the production of Aspergillus niger alpha-glucosidase expressed
      in Pichia pastoris.
AB  - The alpha-glucosidase (AGL) from Aspergillus niger has been applied to produce
      isomaltooligosaccharides. In the present study, various factors which affect the
      yield of recombinant AGL, produced by engineered Pichia pastoris, were
      investigated. The expression level reached 5.5 U ml(-1) in bioreactor after
      optimization of parameters of initial induction cell density, induction
      temperature and methanol concentration. In addition, it was found that
      coexpression of protein disulfide isomerase (PDI) inhibited the growth of the
      engineered P. pastoris strains and had an adverse effect on the production of
      AGL, while codon optimization of native A. niger alpha-glucosidase encoding gene
      (aglu) resulted in a significant enhancement of enzyme production, which reached
      10.1 U ml(-1). We believe that yield of AGL is increased by codon optimization as
      a result of enhanced translation efficiency as well as more stable mRNA secondary
      structure. In contrast, PDI coexpression under the control of alcohol oxidase
      promoter (PAOX1) seems to be less efficient in helping disulfide bond formation
      in AGL while probably induce unfolded protein response, which further leads to
      cell apoptosis and increased protein degradation.

PMID- 23132255
TI  - MCP-1-induced protein-1, an immune regulator.
AB  - MCP-1-induced protein-1 (MCPIP1) is a newly identified protein that is crucial to
      immune regulation. Mice lacking MCPIP1 gene suffer from severe immune disorders,
      and most of them cannot survive longer than 12 weeks. Considerable progress has
      been made in revealing the mechanism underlying the immune regulatory function of
      MCPIP1. MCPIP1 can act as an RNase to promote the mRNA degradation of some
      inflammatory cytokines, such as IL-6 and IL-1. Pre-microRNAs are also confirmed
      to be the substrate of MCPIP1 RNase. The structure of MCPIP1 N-terminal conserved
      domain shows a PilT N-terminus-like RNase structure, further supporting the
      notion that MCPIP1 has RNase activity. MCPIP1 can also deubiquitinate TNF
      receptor-associated factor family proteins, which are known to mediate immune and
      inflammatory responses. In this review, we summarize recent progress on the
      immune regulatory role of MCPIP1 and discuss the mechanisms underlying its
      function.

PMID- 23132257
TI  - [Reduction of lung cancer-associated mortality by computed tomography screening.
      National Lung Screening Trial].

PMID- 23132256
TI  - Regulation of TLR7/9 signaling in plasmacytoid dendritic cells.
AB  - Plasmacytoid dendritic cells (pDCs), also known as type I interferon (IFN)
      producing cells, are specialized immune cells characterized by their
      extraordinary capabilities of mounting rapid and massive type I IFN response to
      nucleic acids derived from virus, bacteria or dead cells. PDCs selectively
      express endosomal Toll-like receptor (TLR) 7 and TLR9, which sense viral RNA and
      DNA respectively. Following type I IFN and cytokine responses, pDCs differentiate
      into antigen presenting cells and acquire the ability to regulate T cell-mediated
      adaptive immunity. The functions of pDCs have been implicated not only in
      antiviral innate immunity but also in immune tolerance, inflammation and tumor
      microenvironments. In this review, we will focus on TLR7/9 signaling and their
      regulation by pDC-specific receptors.

PMID- 23132258
TI  - Targeting FLIP and Mcl-1 using a combination of aspirin and sorafenib sensitizes
      colon cancer cells to TRAIL.
AB  - The multikinase inhibitor sorafenib is highly effective against certain types of
      cancer in the clinic and prevents colon cancer cell proliferation in vitro. Non
      steroidal anti-inflammatory drugs, such as acetylsalicylic acid (aspirin), have
      shown activity against colon cancer cells. The aims of this study were to
      determine whether the combination of aspirin with sorafenib has enhanced anti
      proliferative effects and increases recombinant human tumour necrosis factor
      related apoptosis-inducing ligand (rhTRAIL)-induced apoptosis in the human SW948,
      Lovo, Colo205, Colo320, Caco-2 and HCT116 colon cancer cell lines. In four cell
      lines, aspirin strongly stimulated the anti-proliferative effects of sorafenib
      (~four-fold enhancement) by inducing cell cycle arrest. Furthermore, combining
      low doses of aspirin (<= 5 mm) and sorafenib (<= 2.5 um) greatly sensitized TRAIL
      sensitive and TRAIL-resistant colon cancer cells to rhTRAIL, much more potently
      than either drug combined with rhTRAIL. The increase in rhTRAIL sensitivity was
      due to inhibition of FLIP and Mcl-1 protein expression following aspirin and
      sorafenib co-treatment, as confirmed by knock-down studies. Next, the clinical
      relevance of targeting FLIP and Mcl-1 in colon cancer was examined. Using
      immunohistochemistry, we found that Mcl-1 expression was significantly increased
      in colon adenoma and carcinoma patient material compared to healthy colonic
      epithelium, similar to the enhanced FLIP expression we recently observed in colon
      cancer. These results underscore the potential of combining low doses of aspirin
      with sorafenib to inhibit proliferation and target the anti-apoptotic proteins
      FLIP and Mcl-1 in colon cancer cells.

PMID- 23132259
TI  - Airway closure: nothing good during anesthesia.

PMID- 23132260
TI  - A call for research on sepsis in developing countries.

PMID- 23132261
TI  - The clinical sound of the intensivist.

PMID- 23132262
TI  - Transversus abdominis plane block in combination with general anesthesia provides
      better intraoperative hemodynamic control and quicker recovery than general
      anesthesia alone in high-risk abdominal surgery patients.
AB  - BACKGROUND: Patients with severe cardiovascular disease are frequently
      hemodynamically unstable during abdominal surgery. Improving the safety of such
      patients by stabilizing intraoperative hemodynamics remains a major concern for
      anesthesiologists. Transversus abdominis plane (TAP) block in combination with
      general anesthesia may facilitate optimum anesthetic management of these high
      risk patients. METHODS: Patients with cardiovascular disease classified as
      American Society of Anesthesiologists (ASA) physical status 3 were enrolled. The
      patients were undergoing elective abdominal surgery and were randomized to a
      group receiving general anesthesia and TAP block (Group T, N.=33) or a group
      receiving general anesthesia alone (Group G, N.=35). We compared the groups for
      intraoperative hemodynamic stability, anesthesia emergence time, amounts of
      anesthetics and opioids given, and frequency of emergency treatment with
      cardiovascular agents. A preliminary study demonstrated that systolic blood
      pressure and heart rate were maintained stable within 70-110% of their
      preanesthesia values throughout surgery in ASA 1 elderly patients without
      cardiovascular disease. Thus, the hemodynamically stable time was defined as the
      time when systolic blood pressure and heart rate were 70-110% of their
      preanesthesia values. The ratio of hemodynamically stable time to total operative
      time was used as an index of hemodynamic stability. RESULTS: The median (minimum
      maximum) percentage of hemodynamically stable time was longer in Group T (91[50
      100]%) than Group G (79[40-91]%, P<0.01). The mean sevoflurane concentration,
      amount of fentanyl given and frequency of vasopressor use were lower in Group T
      than Group G (P<0.05). Anesthesia emergence time was shorter in Group T (14[4-30]
      min) than Group G (18[9-52] min, P<0.01). No worsening of cardiovascular
      complications was observed. CONCLUSION: For abdominal surgery in patients with
      severe cardiovascular disease, combining TAP block with general anesthesia
      promotes intraoperative hemodynamic stability and early emergence from
      anesthesia.

PMID- 23132263
TI  - Plasma renin concentration as a predictor of outcome in a medical intensive care
      setting: a retrospective pilot study.
AB  - BACKGROUND: Renin and aldosterone are involved in an organ perfusion pathway that
      may be an estimate of disease severity. The primary objective was to explore the
      relationship between outcome and aldosterone and renin levels at medical
      intensive care unit (MICU) admissions in comparison to SAPS II scores. METHODS:
      This retrospective study was conducted on patients admitted to the adult MICU
      during 12 months. Exclusion: subjects with creatinine >176 mmol/l, chronic
      arrhythmia and ACE-inhibitor therapy. Admission aldosterone and renin plasma
      levels were measured and SAPS II scores were calculated. RESULTS: Eighty-two
      patients were included. Only the plasma renin median concentration difference
      between survivors and non-survivors was significant (P=0.0168). The area under
      the ROC curve for mortality and plasma renin concentration was similar to that of
      SAPS II. The correlation between mortality and renin >84 pg/mL showed an odds
      ratio of 5.78+/-3.45, P=0.003. CONCLUSION: Renin was correlated to outcome in
      critically ill medical patients.

PMID- 23132265
TI  - Thermal decomposition of solution processable metal xanthates on mesoporous
      titanium dioxide films: a new route to quantum-dot sensitised heterojunctions.
AB  - We introduce a straightforward route to the fabrication of metal sulfide
      semiconductor (e.g. CdS, Sb(2)S(3), Bi(2)S(3)) sensitised TiO(2) films. Our
      approach is based upon the controllable thermal decomposition of a single-source
      metal xanthate precursor on a mesoporous metal oxide film. The growth of the
      metal sulfide deposit is confirmed by Raman and UV-Vis steady-state absorption
      measurements. Transient absorption spectroscopy measurements provide evidence for
      charge separation across the metal sulfide/TiO(2) interface. Moreover, a high
      yield of long-lived photogenerated charges is observed in a three-component
      TiO(2)/metal sulfide/spiro-OMeTAD film, thus demonstrating the potential of such
      multicomponent films for solar energy conversion devices.

PMID- 23132266
TI  - A method for determining optimal mean airway pressure in high-frequency
      oscillatory ventilation.
AB  - BACKGROUND: "Optimal" mean airway pressure (MAP) during high-frequency
      oscillatory ventilation (HFOV) can be defined as the pressure that allows for
      maximal alveolar recruitment while minimizing alveolar overdistension. Choosing a
      MAP near or just below the point of maximal curvature (PMC) of the volume
      pressure characteristics of the lung can serve as a guide to avoid overdistention
      during HFOV, while simultaneously preventing derecruitment. The purpose of this
      study was to assess whether optimal MAP at the PMC can be determined by using
      measures of PaO(2) in patients with acute respiratory distress syndrome (ARDS)
      undergoing HFOV. METHODS: We prospectively studied seven patients with ARDS who
      underwent HFOV after failed conventional ventilation. In addition, 11 healthy
      subjects were studied to validate measurements of changes in end-expiratory lung
      volume (?EELV) using magnetometers. Using this validated method, plots of ?EELV
      and MAP were constructed during decremental changes in MAP following a
      recruitment maneuver in seven ventilated patients with ARDS. The PMC was defined
      as the point where the slope of the ?EELV versus MAP curve acutely changed. The
      MAP at the PMC was compared to that determined from plots of PaO(2) versus MAP.
      RESULTS: In the healthy cohort, measurements of ?EELV obtained by magnetometry
      approximated the line of identity when compared to those obtained by spirometry.
      The MAP determined using either the ?EELV or PaO(2) techniques were identical in
      all seven HFOV ventilated patients. Additionally, there was a significant
      correlation between the MAP associated changes in PaO2 and the MAP associated
      changes in ?EELV (p < 0.001). CONCLUSIONS: The finding that MAP at the PMC is the
      same whether determined by measures of ?EELV or PaO(2) suggest that bedside
      measures PaO(2) may provide an acceptable surrogate for measures of EELV when
      determining "optimal" MAP during HFOV.

PMID- 23132267
TI  - Glycine transporter type 1 occupancy by bitopertin: a positron emission
      tomography study in healthy volunteers.
AB  - Deficient N-methyl-D-aspartate (NMDA) receptor transmission is thought to
      underlie schizophrenia. An approach for normalizing glutamate neurotransmission
      by enhancing NMDA receptor transmission is to increase glycine availability by
      inhibiting the glycine transporter type 1 (GlyT1). This study investigated the
      relationship between the plasma concentration of the glycine reuptake inhibitor
      bitopertin (RG1678) and brain GlyT1 occupancy. Healthy male volunteers received
      up to 175 mg bitopertin once daily, for 10-12 days. Three positron emission
      tomography scans, preceded by a single intravenous infusion of ~30 mCi
      [(11)C]RO5013853, were performed: at baseline, on the last day of bitopertin
      treatment, and 2 days after drug discontinuation. Eighteen subjects were
      enrolled. At baseline, regional volume of distribution (V(T)) values were highest
      in the pons, thalamus, and cerebellum (1.7-2.7 ml/cm(3)) and lowest in cortical
      areas (~0.8 ml/cm(3)). V(T) values were reduced to a homogeneous level following
      administration of 175 mg bitopertin. Occupancy values derived by a two-tissue
      five-parameter (2T5P) model, a simplified reference tissue model (SRTM), and a
      pseudoreference tissue model (PRTM) were overall comparable. At steady state, the
      relationship between bitopertin plasma concentration and GlyT1 occupancy derived
      by the 2T5P model, SRTM, and PRTM exhibited an EC(50) of ~190, ~200, and ~130
      ng/ml, respectively. E(max) was ~92% independently of the model used. Bitopertin
      plasma concentration was a reliable predictor of occupancy because the
      concentration-occupancy relationship was superimposable at steady state and 2
      days after drug discontinuation. These data allow understanding of the
      concentration-occupancy-efficacy relationship of bitopertin and support dose
      selection of future molecules.

PMID- 23132268
TI  - Too much of a good thing: blocking noradrenergic facilitation in medial
      prefrontal cortex prevents the detrimental effects of chronic stress on
      cognition.
AB  - Cognitive impairments associated with dysfunction of the medial prefrontal cortex
      (mPFC) are prominent in stress-related psychiatric disorders. We have shown that
      enhancing noradrenergic tone acutely in the rat mPFC facilitated extra
      dimensional (ED) set-shifting on the attentional set-shifting test (AST), whereas
      chronic unpredictable stress (CUS) impaired ED. In this study, we tested the
      hypothesis that the acute facilitatory effect of norepinephrine (NE) in mPFC
      becomes detrimental when activated repeatedly during CUS. Using microdialysis, we
      showed that the release of NE evoked in mPFC by acute stress was unchanged at the
      end of CUS treatment. Thus, to then determine if repeated elicitation of this NE
      activity in mPFC during CUS may have contributed to the ED deficit, we infused a
      cocktail of alpha(1)-, beta(1)-, and beta(2)-adrenergic receptor antagonists into
      the mPFC prior to each CUS session, then tested animals drug free on the AST.
      Antagonist treatment prevented the CUS-induced ED deficit, suggesting that NE
      signaling during CUS compromised mPFC function. We confirmed that this was not
      attributable to sensitization of adrenergic receptor function following chronic
      antagonist treatment, by administering an additional microinjection into the mPFC
      immediately prior to ED testing. Acute antagonist treatment did not reverse the
      beneficial effects of chronic drug treatment during CUS, nor have any effect on
      baseline ED performance in chronic vehicle controls. Thus, we conclude that
      blockade of noradrenergic receptors in mPFC protected against the detrimental
      cognitive effects of CUS, and that repeated elicitation of noradrenergic
      facilitatory activity is one mechanism by which chronic stress may promote mPFC
      cognitive dysfunction.

PMID- 23132269
TI  - Effects of the BDNF Val66Met polymorphism on white matter microstructure in
      healthy adults.
AB  - The BDNF Val(66)Met polymorphism, a possible risk variant for mental disorders,
      is a potent modulator of neural plasticity in humans and has been linked to
      deficits in gray matter structure, function, and cognition. The impact of the
      variant on brain white matter structure, however, is controversial and remains
      poorly understood. Here, we used diffusion tensor imaging to examine the effects
      of BDNF Val(66)Met genotype on white matter microstructure in a sample of 85
      healthy Caucasian adults. We demonstrate decreases of fractional anisotropy and
      widespread increases in radial diffusivity in Val/Val homozygotes compared with
      Met-allele carriers, particularly in prefrontal and occipital pathways. These
      data provide an independent confirmation of prior imaging genetics work, are
      consistent with complex effects of the BDNF Val(66)Met polymorphism on human
      brain structure, and may serve to generate hypotheses about variation in white
      matter microstructure in mental disorders associated with this variant.

PMID- 23132270
TI  - Olanzapine sensitization and clozapine tolerance: from adolescence to adulthood
      in the conditioned avoidance response model.
AB  - Disruption of conditioned avoidance response (CAR) in rodents is one trademark
      feature of many antipsychotic drugs. In adult rats, repeated olanzapine (OLZ)
      treatment causes an enhanced disruption of avoidance response (sensitization),
      whereas repeated clozapine (CLZ) treatment causes a decreased disruption
      (tolerance). The present study addressed (1) whether OLZ sensitization and CLZ
      tolerance can be induced in adolescent rats, and (2) the extent to which OLZ
      sensitization and CLZ tolerance induced in adolescence persists into adulthood.
      Male adolescent Sprague-Dawley rats (approximate postnatal days (~P) 43-47) were
      first treated with OLZ (1.0 or 2.0 mg/kg, subcutaneously (sc)) or CLZ (10 or 20
      mg/kg, sc) daily for 5 consecutive days in the CAR model. They were then tested
      for the expression of OLZ sensitization or CLZ tolerance either in adolescence
      (~P 50) or after they matured into adults (~P 76 and 92) in a challenge test
      during which all rats were injected with either a lower dose of OLZ (0.5 mg/kg)
      or CLZ (5.0 mg/kg). When tested in adolescence, rats previously treated with OLZ
      showed a stronger inhibition of CAR than those previously treated with vehicle
      (ie, sensitization). In contrast, rats previously treated with CLZ showed a
      weaker inhibition of CAR than those previously treated with vehicle (ie,
      tolerance). When tested in adulthood, the OLZ sensitization was still detectable
      at both time points (~P 76 and 92), whereas the CLZ tolerance was only detectable
      on ~P 76, and only manifested in the intertrial crossing. Performance in the
      prepulse inhibition and fear-induced 22 kHz ultrasonic vocalizations in adulthood
      were not altered by adolescence drug treatment. Collectively, these findings
      suggest that atypical antipsychotic treatment during adolescence can induce a
      long-term specific alteration in antipsychotic effect that persists into
      adulthood despite the brain maturation. As antipsychotic drugs are being
      increasingly used in children and adolescents in the past two decades, findings
      from this study are important for understanding the impacts of adolescent
      antipsychotic treatment on the brain and behavioral developments. This work also
      has implications for clinical practice involving adolescence antipsychotic
      treatments in terms of drug choice, drug dose, and schedule.

PMID- 23132271
TI  - Convergent findings for abnormalities of the NF-kappaB signaling pathway in
      schizophrenia.
AB  - Neurons exhibit a constitutive level of nuclear factor-kappaB (NF-kappaB)
      signaling and this pathway plays a significant role in neurite outgrowth,
      activity-dependent plasticity, and cognitive function. Transcription factor
      analysis was performed in a microarray data set profiled in four different brain
      regions (n=54 comparison group; n=53 schizophrenia (SZ)). An independent
      postmortem cohort was used for gene expression (n=24 comparison group; n=22 SZ),
      protein abundance (n=8 comparison group; n=8 SZ), and NF-kappaB nuclear activity
      (n=10 comparison group; n=10 SZ) quantification. Expression quantitative trait
      locus analysis was performed using publicly available data. Prepulse inhibition
      (PPI) of the acoustic startle reflex was tested in healthy individuals (n=690).
      Comparison of microarray data showed that NF-kappaB was among the transcription
      factors associated with the differential expression of genes in cases vs
      controls. NF-kappaB gene and protein levels and nuclear activation were
      significantly decreased in the superior temporal gyrus of patients with SZ.
      Upstream NF-kappaB genes related to translocation were significantly dysregulated
      in SZ. The gene expression levels of an NF-kappaB-associated importin (KPNA4: one
      of the proteins responsible for the translocation of NF-kappaB to the nucleus)
      was decreased in SZ and an SNP within the KPNA4 locus was associated with
      susceptibility to SZ, reduced KPNA4 expression levels and attenuated PPI of the
      startle reflex in healthy control subjects. These findings implicate
      abnormalities of the NF-kappaB signaling pathway in SZ and provide evidence for
      an additional possible mechanism affecting the translocation of NF-kappaB
      signaling to the nucleus.

PMID- 23132272
TI  - Motor difficulties in autism spectrum disorder: linking symptom severity and
      postural stability.
AB  - Postural stability is a fundamental aspect of motor ability that allows
      individuals to sustain and maintain the desired physical position of one's body.
      The present study examined postural stability in average-IQ adolescents and
      adults with Autism Spectrum Disorder (ASD). Twenty-six individuals with ASD and
      26 age-and-IQ-matched individuals with typical development stood on one leg or
      two legs with eyes opened or closed on a Wii balance board. Results indicated
      significant group differences in postural stability during one-legged standing,
      but there were no significant group differences during two-legged standing. This
      suggests that static balance during more complex standing postures is impaired in
      average-IQ individuals with ASD. Further, current ASD symptoms were related to
      postural stability during two-legged standing in individuals with ASD. Future
      directions and clinical implications are discussed.

PMID- 23132273
TI  - Brief report: Effect of spatial complexity on visual short-term memory and self
      reported autistic-like traits in typically developed individuals.
AB  - This report examines effects of the spatial complexity of configurations on
      visual short-term memory (VSTM) capacity for individuals from the general
      population differing on autism-spectrum quotient (AQ) scores. During each trial,
      nine-line segments with various orientations were arrayed in simple or complex
      configurations and presented in both memory and test displays. Typically, VSTM
      capacity decreases with increasing configuration complexity. We found that VSTM
      capacity for simple configurations was larger than for complex configurations in
      individuals reporting low AQ, whereas for individuals reporting high AQ, there
      were no significant differences between these configurations. These results
      suggest that the effects of spatial complexity on VSTM capacity could be observed
      in individuals reporting low AQ, but not in individuals reporting high AQ.

PMID- 23132274
TI  - Important aspects of urine sampling for angiotensinogen measurement: time and
      preservation conditions in healthy individuals.
AB  - Intrarenal renin-angiotensin system (RAS) plays an important role for the
      pathogenesis of renal injuries.  Experimental studies have demonstrated that
      angiotensinogen levels in renal tissues reflect the activity of intrarenal RAS. 
      However, dynamics of urinary angiotensinogen have not been investigated in
      detail.  Therefore, we examined the preservation conditions of the measured
      values of urinary angiotensinogen concentrations and an ultradian rhythm of
      urinary angiotensinogen excretion in humans.  Urine samples were collected from
      24 healthy volunteers.  The urinary concentrations of angiotensinogen were
      measured by using ELISA.  Two different urine preservation conditions were
      examined.  One cycle of freeze-and-thaw did not change the measured values of
      urinary angiotensinogen concentrations.  Moreover, to keep urine samples at room
      temperature for 12 hours did not change the measured values of urinary
      angiotensinogen concentrations.  Thus, preservation conditions do not change the
      measured values of urinary angiotensinogen concentrations.  Regarding an
      ultradian rhythm, blood pressure and the urinary concentrations of
      angiotensinogen were measured at 09:00, 13:00, and 16:00.  The averaged levels of
      blood pressure were similar over the time.  The average of urinary
      angiotensinogen/creatinine (Cr) ratios was 8.73 +/- 1.15 ng/mg Cr at 09:00, 9.53
      +/- 1.58 ng/mg Cr at 13:00, and 8.58 +/- 1.26 ng/mg Cr at 16:00.  The urinary
      angiotensinogen excretion in healthy volunteers does not have an ultradian change
      during the daytime (P = 0.482).  This may be another indication that the
      intrarenal RAS is independent of the systemic RAS.  We have to pay attention to
      these findings in handling urine samples for measurements of angiotensinogen.

PMID- 23132275
TI  - MicroRNA profiling in great saphenous vein tissues of patients with chronic
      venous insufficiency.
AB  - Chronic venous insufficiency (CVI) is a common disease characterized by
      structural and functional abnormalities of the venous system.  Until recently,
      the pathogenesis of CVI remains largely unknown.  MicroRNAs (miRNAs) are a family
      of endogenous small non-coding RNAs emerged as post-transcriptional gene
      repressors and play essential roles in diverse pathological processes including
      vascular disease.  However, their roles in CVI have not been elucidated.  In this
      study, we employed oligonucleotide microarrays to perform a genome-wide miRNAs
      profiling in the great saphenous vein (GSV) tissues of patients with CVI.  Our
      results revealed a total of 14 miRNAs that are expressed differentially in GSV
      tissues.  Among them nine miRNAs were found significantly up-regulated, while
      five miRNAs were down-regulated significantly.  Real-time RT-PCR verified
      statistically consistent expression of three selected miRNAs (miR-34a, miR-155
      and miR-202) with microarrays analysis.  These three miRNAs, which were described
      as crucial regulators in many biological processes and vascular diseases, might
      also play important roles in CVI.  Functional annotation of target genes of
      differentially expressed miRNAs via bioinformatics approaches revealed that these
      predicted targets were significantly enriched and involved in several key
      signaling pathways important for CVI, including mitogen-activated protein kinase
      pathways, pathways in cancer, apoptosis, and cell cycle, and p53 signaling
      pathways.  In summary, miRNAs might involve in multiple signaling pathways
      contributing to the pathological processes of CVI.  These data may provide
      fundamental insights into the molecular basis of CVI, which may aid in designing
      novel approaches for prevention and treatment of this complex disease.

PMID- 23132276
TI  - Activation of Bacillus spores at moderately elevated temperatures (30-33  degrees
      C).
AB  - The time/temperature profiles experienced by spores on the track from their
      natural sporulation environment to consumable food products may be highly
      diverse. Temperature has been documented as an important factor that may activate
      spores, i.e. potentiates spores to germinate. There is, however, limited
      knowledge about the relationship between the expected temperature history and the
      subsequent germination characteristics of bacterial spores. We show here that the
      germination rate of five different Bacillus spore populations, represented by
      strains of Bacillus cereus, Bacillus weihenstephanensis, Bacillus pumilus,
      Bacillus licheniformis and Bacillus subtilis could be increased following 1 week
      storage at moderately elevated temperatures, 30-33  degrees C, compared to spores
      stored at 3-8  degrees C. The results imply that spores contamination routes to
      foods, specifically the temperature history, could be highly relevant data in
      predictive modeling of food spoilage and safety. Activation at these moderately
      elevated temperatures may be a native form of spore activation in their natural
      habitats, knowledge that also could be useful in development of decontamination
      strategies for mildly heated foods.

PMID- 23132277
TI  - Selection and characterization of a newly isolated thermotolerant Pichia
      kudriavzevii strain for ethanol production at high temperature from cassava
      starch hydrolysate.
AB  - Pichia kudriavzevii DMKU 3-ET15 was isolated from traditional fermented pork
      sausage by an enrichment technique in a yeast extract peptone dextrose (YPD)
      broth, supplemented with 4 % (v/v) ethanol at 40  degrees C and selected based on
      its ethanol fermentation ability at 40  degrees C in YPD broth composed of 16 %
      glucose, and in a cassava starch hydrolysate medium composed of cassava starch
      hydrolysate adjusted to 16 % glucose. The strain produced ethanol from cassava
      starch hydrolysate at a high temperature up to 45  degrees C, but the optimal
      temperature for ethanol production was at 40  degrees C. Ethanol production by
      this strain using shaking flask cultivation was the highest in a medium
      containing cassava starch hydrolysate adjusted to 18 % glucose, 0.05 %
      (NH(4))(2)SO(4), 0.09 % yeast extract, 0.05 % KH(2)PO(4), and 0.05 %
      MgSO(4).7H(2)O, with a pH of 5.0 at 40  degrees C. The highest ethanol
      concentration reached 7.86 % (w/v) after 24 h, with productivity of 3.28 g/l/h
      and yield of 85.4 % of the theoretical yield. At 42  degrees C, ethanol
      production by this strain became slightly lower, while at 45  degrees C only 3.82
      % (w/v) of ethanol, 1.27 g/l/h productivity and 41.5 % of the theoretical yield
      were attained. In a study on ethanol production in a 2.5-l jar fermenter with an
      agitation speed of 300 rpm and an aeration rate of 0.1 vvm throughout the
      fermentation, P. kudriavzevii DMKU 3-ET15 yielded a final ethanol concentration
      of 7.35 % (w/v) after 33 h, a productivity of 2.23 g/l/h and a yield of 79.9 % of
      the theoretical yield.

PMID- 23132278
TI  - Large scale MALDI-TOF MS based taxa identification to identify novel pigment
      producers in a marine bacterial culture collection.
AB  - A challenge in the rational exploitation of microbial culture collections is to
      avoid superfluous testing of replicas. MALDI-TOF MS has been shown to be an
      efficient dereplication tool as it can be used to discriminate between bacterial
      isolates at the species level. A bacterial culture collection of more than 10,000
      heterotrophic marine bacterial isolates from sea-water surface layers of the
      Norwegian Trondheimsfjord and neighbouring coastal areas has been established. A
      sub-collection of pigmented isolates was earlier screened for novel carotenoids
      with UVA-Blue light absorbing properties. This was a comprehensive analytical
      task and it was observed that a significant number of extracts with identical
      pigment profile were recovered. Hence, this study was undertaken to explore the
      use of MALDI-TOF MS as a dereplication tool to quickly characterize the bacterial
      collection. Furthermore, LC-DAD-MS analysis of pigment profiles was performed to
      check if pigment profile diversity was maintained among isolates kept after the
      potential MALDI-TOF MS selection step. Four hundred isolates comprising both
      pigmented and non-pigmented isolates were used for this study. The resulting
      MALDI-TOF MS dendrogram clearly identified a diversity of different taxa and
      these were supported by the pigment profile clustering, thus linking the pigment
      production as species-specific properties. Although one exception was found, it
      can be concluded that MALDI-TOF MS dereplication is a promising pre-screening
      tool for more efficient screening of microbial culture collection containing
      pigments with potential novel properties.

PMID- 23132279
TI  - Spongiimonas flava gen. nov., sp. nov., a new member of the family
      Flavobacteriaceae isolated from an unidentified marine sponge.
AB  - A Gram-negative, strictly aerobic, golden-yellow pigmented, non-motile, rod
      shaped strain designated J36A-7(T) was isolated from an unidentified yellow-green
      coloured marine sponge. Phylogenetic analyses based on the 16S rRNA gene sequence
      revealed that the novel isolate was affiliated with the family Flavobacteriaceae
      of the phylum Bacteroidetes and that it showed highest sequence similarity (85.6
      %) to Nonlabens dokdonensis DSW-6(T). The strain could be differentiated
      phenotypically from recognized members of the family Flavobacteriaceae. The major
      fatty acids of strain J36A-7(T) were identified as iso-C16:0, iso-C17:0 3-OH and
      summed feature three as defined by the MIDI system (C16:1 omega7c and/or iso
      C15:0 2-OH). The DNA G+C content was determined to be 31.2 mol%, the major
      respiratory quinone was identified as menaquinone 6 (MK-6) and a complex polar
      lipid profile was present consisting of phosphatidylethanolamine, two
      unidentified glycolipids, one unidentified aminolipid and one unidentified lipid.
      From the distinct phylogenetic position and combination of genotypic and
      phenotypic characteristics, the strain is considered to represent a novel genus
      for which the name Spongiimonas flava gen. nov., sp. nov. is proposed. The type
      strain of S. flava is J36A-7(T) (=KCTC 32176(T) = NBRC 109319(T)).

PMID- 23132280
TI  - Evaluation of corticospinal excitability in cervical myelopathy, before and after
      surgery, with transcranial magnetic stimulation: a pilot study.
AB  - PURPOSE: A pilot study to examine the impact of cervical myelopathy on
      corticospinal excitability, using transcranial magnetic stimulation, and to
      investigate whether motor evoked potential (MEP) and silent period (SP)
      recruitment curve (RC) parameters can detect changes in corticospinal function
      pre- and post-surgery. METHODS: We studied six cervical myelopathy patients
      undergoing surgery and six healthy controls. Clinical and functional scores and
      neurophysiological parameters were examined prior to and 3 months following the
      surgery. RESULTS: MEP latencies for abductor pollicis brevis (APB) and tibialis
      anterior (TA) muscles and central motor conduction time were prolonged pre- and
      post-surgery; SP durations were differentially altered. There were significant
      differences in parameters of RCs for (1) MEP area in APB (max values, S50) and TA
      (slope) between controls and patients pre- and post-surgery and (2) SP duration
      in APB (max values) between patients pre-surgery and controls. CONCLUSIONS: The
      findings of this pilot study suggest an uncoupling of excitatory and inhibitory
      pathways, which persists at 3 months following cord decompression. RCs for MEP
      and SP at 3 months provide more information on the functional status of the cord
      and prompts for a longer term follow-up.

PMID- 23132281
TI  - Application triangular osteosynthesis for vertical unstable sacral fractures.
AB  - PURPOSE: The aim of this study was to explore the operative technique and
      effectiveness of triangular osteosynthesis for vertically unstable sacral
      fractures. METHODS: From January 2009 to December 2010, 25 vertical unstable
      sacral fractures in 22 patients were treated with triangular osteosynthesis using
      the combination of universal spine system and iliosacral screw in our
      institution. Patients were followed up prospectively with routine post-operation
      visits for clinical and radiographic examination. The reduction quality was
      evaluated according to Matta criterion. Clinical function outcome, and nerve
      function outcome was evaluated by Majeed and Gibbons criterion. RESULTS: All
      patients were followed up for an average of 14 months (range 8-26 months). Local
      infection was seen in two patients, and both were healed with debridement and
      antibiotics. Patients experienced early weight-bearing ability, no fracture
      reduction loss, and hardware loosening, while all fractures appeared as bone
      union at the final follow-up. According to Matta criterion for fracture
      reduction, the results were excellent in 18 sides, good in 6 sides, and fair in 1
      side. According to Majeed functional scoring at last follow-up, the results were
      excellent in 13 cases, good in 6 cases, fair in 2 cases, and poor in 1 case.
      Neurologic impairment was noted in 13 patients pre-operative, six patients
      achieved complete recovery, six patients achieved partial improvement, one
      patient did not have any improvement at the last follow-up. CONCLUSION:
      Triangular osteosynthesis is a relatively new fixation for vertical unstable
      sacral fractures, the fixation is rigid, permits early full weight-bearing, and
      nerve decompression can be performed, which facilitates function recovery.

PMID- 23132283
TI  - Development and application of an optical sensor for ethene in ambient air using
      near infra-red cavity ring down spectroscopy and sample preconcentration.
AB  - An automated near infra-red (IR) continuous wave cavity ring down spectrometer
      with sample preconcentration has been developed for the measurement of ethene
      (C2H4) in air. The spectrometer incorporated a distributed feedback diode laser
      operating at wavelengths lambda~ 1.6 MUm and a pre-concentration system
      containing an adsorbent, molecular sieve 4A (MS4A). An absorption line located at
      6148.58 cm-1, and free from spectral overlap with other atmospheric molecules,
      was used for ethene detection. The spectrometer has a capacity for determination
      of atmospheric ethene mixing ratios at half hour time intervals, with a detection
      limit (2 SD above baseline noise) of 280 ppt. Both weekday and weekend
      measurements were performed in ambient air for periods of up to 30 hours. Average
      daytime mixing ratios of ethene were observed to be 2 ppbv and 1 ppbv during
      weekdays and weekends respectively. The mixing ratios of ethene varied from 0.6
      ppbv to 1.2 ppbv in Bristol air during the weekend, with influence of
      meteorological conditions. The observed variations are discussed with
      consideration of probable sources and various meteorological parameters. A
      correlation is observed in the mixing ratio of ethene and nitrogen dioxide.

PMID- 23132282
TI  - Probing myo-inositol 1-phosphate synthase with multisubstrate adducts.
AB  - The synthesis of a series of carbohydrate-nucleotide hybrids, designed to be
      multisubstrate adducts mimicking myo-inositol 1-phosphate synthase first
      oxidative transition state, is reported. Their ability to inhibit the synthase
      has been assessed and results have been rationalised computationally to estimate
      their likely binding mode.

PMID- 23132284
TI  - Cognitive impairment and dementia in late-life bipolar disorder.
AB  - PURPOSE OF REVIEW: This work aims to review the most recent publications on
      cognitive impairment and dementia associated with bipolar disorder (BPD),
      especially in the elderly. RECENT FINDINGS: In the last years, a growing number
      of studies aiming at better understanding of cognitive impairment in BPD were
      found. Impairments found in BPD were compared with other psychiatric disorders
      and primary cognitive diseases. The impact of cognitive impairment on
      functionality was also recently highlighted. With respect to neurobiology,
      studies that explored inflammatory, neurotrophic and pathological cascades
      possibly associated with BPD and cognition were published. Finally, the first
      study covering treatment of cognitive impairment was carried out with
      pramipexole, and it raised important methodological issues for future research in
      BPD. SUMMARY: Cognitive impairment and dementia in BPD should be better explored
      with cognitive and functionality protocols along with biological and neuroimaging
      markers.

PMID- 23132285
TI  - In vitro cell transformation assays for an integrated, alternative assessment of
      carcinogenicity: a data-based analysis.
AB  - The study of the chemical carcinogenesis mechanisms and the design of efficient
      prevention strategies and measures are of crucial importance to protect human
      health. The long-term carcinogenesis bioassays have played a central role in
      protecting human health, but for ethical and practical reasons their use is
      dramatically diminishing, and the genotoxicity short-term tests have taken the
      pivotal role in the pre-screening of carcinogenicity. However, there is evidence
      that this strategy is not sensitive enough to detect all genotoxic carcinogens
      and it cannot detect nongenotoxic carcinogens. In a previous article, we have
      shown that an integrated strategy consisting of the in vitro Ames and Syrian
      Hamster Embryo cells transformation assays, combined with structure-activity
      relationships, is a valid alternative to the present pre-screening strategies.
      Here, we expand the previous investigation by (i) including results of cell
      transformation assays on inorganics, together with an additional assay (Bhas 42),
      and (ii) considering new structural alerts for nongenotoxic carcinogenicity. We
      also present a new analysis on global relationships between toxicological
      endpoints. The new results confirm that the previously proposed integrated,
      alternative strategy is an efficient tool to identify both genotoxic and
      nongenotoxic carcinogens, with an estimated 90-95% sensitivity.

PMID- 23132287
TI  - The effect of hydrogen bond reorganization and equivalent weight on proton
      transfer in 3M perfluorosulfonic acid ionomers.
AB  - We present an investigation into the energetics associated with proton transfer
      in ionomeric fragments of the 3MTM perfluorosulfonic acid (PFSA) membrane at
      different equivalent weights (EW). Electronic structure calculations were
      performed on two fragments each with two pendant side chains separated along a
      poly(tetrafluoroethylene) (PTFE) backbone with chemical formula CF(3)CF(
      O(CF(2))(4)SO(3)H)(CF(2))(n)CF(-O(CF(2))(4)SO(3)H)CF(3), where n = 5 or 7,
      corresponding to membrane equivalent weights of 590 and 690 g mol(-1). Potential
      energy surface (PES) scans were performed for the transfer of a proton in various
      hydrogen bonds between water molecules, sulfonic acid groups, and charged
      species. The scans involved incrementally increasing an O-H bond length in steps
      of 0.02 A with geometry optimizations performed at each step at the B3LYP/6-31G**
      level over all other degrees of freedom. The nature of the hydrogen bond network
      and the degree of dissociation were found to be critical factors in determining
      the resulting energetic barrier for proton transfer. The smaller fragment was
      found to more readily reorient to compensate for the transfer of charge resulting
      in a lower energetic barrier to proton transfer through stabilization of the new
      hydrogen bonds. However, when each ionomer had the same degree of dissociation,
      reprotonation of the sulfonate groups was the most energetically unfavorable in
      EW 590 when no structural reorganization was observed to occur due to its greater
      propensity to exist in a dissociated state.

PMID- 23132286
TI  - DNA damage response in monozygotic twins discordant for smoking habits.
AB  - Previous studies in twins indicate that non-shared environment, beyond genetic
      factors, contributes substantially to individual variation in mutagen
      sensitivity; however, the role of specific causative factors (e.g. tobacco smoke,
      diet) was not elucidated. In this investigation, a population of 22 couples of
      monozygotic twins with discordant smoking habits was selected with the aim of
      evaluating the influence of tobacco smoke on individual response to DNA damage.
      The study design virtually eliminated the contribution of genetic heterogeneity
      to the intra-pair variation in DNA damage response, and thus any difference in
      the end-points investigated could directly be attributed to the non-shared
      environment experienced by co-twins, which included as main factor cigarette
      smoke exposure. Peripheral lymphocytes of study subjects were challenged ex vivo
      with gamma-rays, and the induction, processing, fixation of DNA damage evaluated
      through multiple approaches. Folate status of study subjects was considered
      significant covariate since it is affected by smoking habits and can influence
      radiosensitivity. Similar responses were elicited by gamma-rays in co-twins for
      all the end-points analysed, despite their discordant smoking habits. Folate
      status did not modify DNA damage response, even though a combined effect of
      smoking habits, low-plasma folic acid level, and ionising radiation was observed
      on apoptosis. A possible modulation of DNA damage response by duration and
      intensity of tobacco smoke exposure was suggested by Comet assay and micronucleus
      data, but the effect was quantitatively limited. Overall, the results obtained
      indicate that differences in smoking habits do not contribute to a large extent
      to inter-individual variability in the response to radiation-induced DNA damage
      observed in healthy human populations.

PMID- 23132288
TI  - Evaluation of a surrogate marker: validity and efficiency.
AB  - Statistical validation of a surrogate endpoint or surrogate marker has been
      studied for three decades. However, there is still no consensus on how to
      evaluate surrogate endpoints or surrogate markers. There is much confusion on
      which method should be used for the evaluation of a surrogate endpoint or
      surrogate marker. In this article, we clarify the statistical definitions of the
      surrogate endpoint and surrogate marker and introduce the concept of the validity
      and efficiency of a surrogate marker. We suggest the proportion of information
      gain can be used to evaluate the validity of a surrogate marker.

PMID- 23132289
TI  - DFT investigations of the hydrogenation effect on silicene/graphene hybrids.
AB  - We report here a study on the effect of hydrogenation on a new one-atom  thick
      material made of silicon and carbon atoms (silicene/graphene (SG) hybrid) within
      density functional theory. The structural, electronic and magnetic properties are
      investigated for non-, semi- and fully hydrogenated SG hybrids in a chair
      configuration and are compared with their parent materials. Calculations reveal
      that pure SG is a non-zero band gap semi-conductor with stable planar honeycomb
      structure. So mixing C and Si in an alternating manner gives another way to
      generate a finite band gap in one-atom thick materials. Fully hydrogenation makes
      the gap larger; however half chemical modification with H reduces the gap in
      favor of ferromagnetism order. The findings of this work open a wide spectrum of
      possibilities for designing SG-based nanodevices with controlled and tuned
      properties.

PMID- 23132290
TI  - Attrition rates, reasons, and predictive factors in supportive care and
      palliative oncology clinical trials.
AB  - BACKGROUND: Attrition is common among supportive care/palliative oncology
      clinical trials. However, to the authors' knowledge, few studies to date have
      documented the reasons and predictors for dropout. In the current study, the
      authors' objective was to determine the rate, reasons, and factors associated
      with attrition both before reaching the primary endpoint and at the end of the
      study. METHODS: A review of all prospective interventional supportive
      care/palliative oncology trials conducted in the Department of Palliative Care
      and Rehabilitation Medicine at The University of Texas MD Anderson Cancer Center
      in Houston between 1999 and 2011 was performed. Patient and study characteristics
      and attrition data were extracted. RESULTS: A total of 1214 patients were
      included in 18 clinical trials. The median age of the patients was 60 years.
      Approximately 41% had an Eastern Cooperative Oncology Group performance status of
      >= 3, a median Edmonton Symptom Assessment Scale (ESAS) for fatigue of 7 of 10,
      and a median ESAS for dyspnea of 2 of 10. The attrition rate was 26% (95%
      confidence interval [95% CI], 23%-28%) for the primary endpoint and 44% (95% CI,
      41%-47%) for the end of the study. Common reasons for primary endpoint dropout
      were symptom burden (21%), patient preference (15%), hospitalization (10%), and
      death (6%). Primary endpoint attrition was associated with a higher baseline
      intensity of fatigue (odds ratio [OR], 1.10 per point; P = .01) and a longer
      study duration (P = .04). End-of-study attrition was associated with higher
      baseline levels of dyspnea (OR, 1.06; P = .01), fatigue (OR, 1.08; P = .01),
      Hispanic race (OR, 1.87; P = .002), higher level of education (P = .02), longer
      study duration (P = .01), and outpatient studies (P = 0.05). CONCLUSIONS: The
      attrition rate was high in supportive care/palliative oncology clinical trials,
      and was associated with various patient characteristics and a high baseline
      symptom burden. These findings have implications for future clinical trial design
      including eligibility criteria and sample size calculation.

PMID- 23132291
TI  - Association of TLR5 sequence variants and mRNA level with cytokine transcription
      in pigs.
AB  - The Toll-like receptor 5 (TLR5) plays a crucial role in host defense against
      flagellated bacteria by recognizing flagellin. Accumulating evidence suggests
      that single nucleotide polymorphisms (SNPs) in TLR5 have an effect on flagellin
      recognition and are associated with susceptibility/resistance to disease. In this
      study, we analyzed association of SNPs, including c.834T>G, c.1065T>C, c.1205C>T,
      c.1246A>T, c.1269G>A, and c.1398C>T, as well as mRNA level of TLR5 with the
      abundance of transcripts of cytokines in pigs. SNPs c.1246A>T and c.1269G>A were
      significantly associated with the transcript abundance of interleukin (IL)-2, and
      SNPs c.834T>G and c.1398C>T with IL-10 (P < 0.05); the haplotypes showed a
      tendency to affect the transcript abundance of IL-10 (P = 0.0660) and
      significantly associated with the transcription of TLR5 (P < 0.01); the abundance
      of transcripts of TLR5 and IL-10 were strongly correlated (P < 0.01). The results
      indicated that the SNPs, associated with the transcript abundance of cytokines,
      were related to immune responsiveness mediated by cytokine, which, in turn, would
      have a role in pig breeding for disease resistance. Furthermore, the positive
      correlation between the abundance of TLR5 and IL10 suggest a link between TLR5
      activation and IL-10 expression in porcine.

PMID- 23132292
TI  - Evaluation of image enhancement software as a method of performing half-count
      bone scans.
AB  - Reducing the radiation dose and scanning time of diagnostic tests is often
      desirable. One method uses image enhancement software such as Pixon, which
      processes lower-count scans and aims to produce high-quality images. However, it
      is essential that diagnostic accuracy is not compromised. We compared the level
      of agreement between clinicians using standard scans, with half-count and Pixon
      enhanced half-count scans. Bone scans from 150 patients referred to diagnose
      metastatic disease were degraded by a process of Poisson-preserving binomial
      resampling to generate equivalent half-count scans and then processed by Pixon
      software to recreate 'original' high-quality scans. Two experienced clinicians
      reported the scans in a randomized, blinded manner for metastatic disease
      (yes/no) and assigned a confidence level to this diagnosis. Levels of agreement
      between clinicians were calculated for the full-count, half-count, and Pixon
      enhanced half-count scans and between scanning methods for each clinician.
      Agreement between clinicians for standard full-count scans was 92% (+/-4%,
      kappa=0.80), compared with 92% (+/-4%, kappa=0.79) for half-count scans and 87%
      (+/-5%, kappa=0.70) for Pixon-processed half-count scans. Agreement for a single
      clinician viewing full-count versus half-count scans was 95% (+/-2%, kappa=0.88),
      similar to the agreement for a single clinician viewing full-count versus Pixon
      processed half-count scans (95%, +/-2%, kappa=0.88). With respect to confidence
      in diagnosis, 127 full-count scans were scored in the highest category, compared
      with 98 half-count and 88 Pixon-processed half-count scans. Switching to half
      count scanning does not introduce more diagnostic disagreement than is already
      present between clinicians. However, clinicians feel less confident reporting
      half-count scans. The Pixon enhancement step improved neither objective
      diagnostic agreement nor clinician confidence.

PMID- 23132293
TI  - Polymorphism of 8q24 rsl3281615 and breast cancer risk : a meta-analysis.
AB  - Several genome-wide association studies on breast cancer have reported similar
      findings of a new cancer susceptibility locus, 8q24 rsl3281615. Subsequent case
      control studies have rapidly investigated the association between the single
      nucleotide polymorphism of rsl3281615 at chromosome 8q24 and breast cancer risk,
      but the effect of 8q24 rsl3281615 polymorphism on breast cancer is still unclear
      due to the inconsistence among those studies. Given the contradictory findings, a
      meta-analysis was performed to determine the association between 8q24 rsl3281615
      polymorphism and breast cancer risk. 12 eligible case-control studies with a
      total of 42,508 cases and 53,928 controls were finally included into this meta
      analysis by searching the PubMed, Embase, and China Biology Medicine (CBM)
      databases. We estimated the summary odds ratio (OR) with its corresponding 95 %
      confidence interval (95 % CI) to assess this association. Meta-analyses of total
      12 studies showed 8q24 rsl3281615 polymorphism was significantly associated with
      an increased risk of breast cancer in all contrast models (OR(G vs. A) = 1.10, 95
      % CI 1.05-1.14, P (OR) < 0.001; OR(GG vs. AA) = 1.20, 95 % CI 1.11-1.29, P (OR) <
      0.001; OR(AG vs. AA) = 1.08, 95 % CI 1.05-1.12, P (OR) < 0.001; OR(GG vs. AA +AG)
      = 1.13, 95 % CI 1.07-1.19, P (OR) < 0.001; OR(GG+AG vs. AA) = 1.13, 95 % CI 1.07
      1.19, P (OR) < 0.001). Meta-analyses of studies with high quality showed that
      8q24 rsl3281615 polymorphism was still significantly associated with an increased
      risk of breast cancer under the five genetic contrast models. Sensitivity
      analyses by sequential omission of any individual studies and subgroup analyses
      by ethnicity further identified the significant association between 8q24
      rsl3281615 polymorphism and breast cancer risk. Conclusively, this meta-analysis
      shows a significant association between 8q24 rsl3281615 polymorphism and breast
      cancer risk.

PMID- 23132294
TI  - KiSS-1 methylation and protein expression patterns contribute to diagnostic and
      prognostic assessments in tissue specimens for colorectal cancer.
AB  - KISS1 is a metastasis suppressor lost in several solid malignancies. We evaluated
      the clinical relevance of KiSS-1 methylation and its protein expression in
      colorectal cancer. The epigenetic silencing of KiSS-1 by hypermethylation was
      tested in colon cancer cells (n = 5) before and after azacytidine treatment. KiSS
      1 methylation was evaluated by methylation-specific PCR in colorectal cancer
      cells, and normal, benign, and tumor tissues (n = 352) were grouped in a training
      set (n = 62) and two independent validation cohorts (n = 100 and n = 190). KiSS-1
      protein expression was analyzed by immunohistochemistry on tissue arrays. KiSS-1
      hypermethylation correlated with transcript and protein expression loss, being
      increased in vitro by azacytidine. Methylation rates were 53.1, 70.0, and 80.0 %
      in the training and validation sets, respectively. In the training set, KiSS-1
      methylation rendered a diagnostic accuracy of 72.7 % (p = 0.002). Combination of
      KiSS-1 methylation and serum CEA (p = 0.001) increased the prognostic utility of
      CEA alone (p = 0.022). In the first validation set, KiSS-1 methylation correlated
      with tumor grade (p = 0.011), predicted recurrence (p = 0.009), metastasis (p =
      0.004), disease-free (p = 0.034), and overall survival (p = 0.015). In the second
      validation cohort, KiSS-1 methylation predicted disease-specific survival (p =
      0.030). In the training set, cytoplasmic KiSS-1 expression was significantly
      higher in nonneoplastic biopsies as compared to colorectal tumors (p < 0.0005).
      In the validation set, loss of cytoplasmic expression correlated with tumor stage
      (p = 0.007), grade (p = 0.035), recurrence (p = 0.017), and disease-specific
      survival (p = 0.022). KiSS-1 was revealed epigenetically modified in colorectal
      cancer. The diagnostic and prognostic utility of KiSS-1 methylation and
      expression patterns suggests their assessment for the clinical management of
      colorectal cancer patients.

PMID- 23132295
TI  - Overexpression of GOLPH3 is associated with poor clinical outcome in gastric
      cancer.
AB  - This study aims to investigate the expression and significance of GOLPH3 in human
      gastric cancer progression and prognosis. Using immunohistochemistry (IHC) and
      real-time reverse transcriptase polymerase chain reaction assay, we identified
      abnormally elevated expression of GOLPH3 in gastric cancer tissues compared to
      paired normal stomach mucosa tissues in 40 patients. In addition, the enzyme
      linked immunosorbent assay (ELISA) was used to quantify serum GOLPH3
      concentrations in the same 40 gastric cancer patients and 40 healthy individuals.
      ELISA revealed significantly higher serum concentrations of GOLPH3 in gastric
      cancer patients compared to healthy individuals (p = 0.002). In order to
      investigate the correlations between GOLPH3 and the clinicopathological features
      of gastric cancer, the expression of GOLPH3 in 123 gastric cancer patients were
      detected by IHC, and the results showed that overexpression of GOLPH3 was
      associated with the size of the tumor (p = 0.013), histological grade (p =
      0.002), depth of invasion (p < 0.001), lymph node metastasis (p < 0.001), distant
      metastasis (p = 0.018), and TNM stage (p < 0.001). Kaplan-Meier survival analysis
      showed that high GOLPH3 expression exhibited a significant correlation with poor
      prognosis for gastric cancer patients. Further, Cox multivariate analysis
      indicated that GOLPH3 expression level was an independent prognostic factor for
      patients after radical resection. In conclusion, the overexpression of GOLPH3 is
      closely related to the progression of gastric cancer and might be regarded as an
      independent predictor of poor prognosis for gastric cancer.

PMID- 23132296
TI  - Heavy metal scavenger metallothionein mitigates deep hypothermia-induced
      myocardial contractile anomalies: role of autophagy.
AB  - Low-ambient temperature environment exposure increased the risk of cardiovascular
      morbidity and mortality, although the underlying mechanism remains unclear. This
      study was designed to examine the impact of cardiac overexpression of
      metallothionein, a cysteine-rich heavy metal scavenger, on low temperature (4
      degrees C)-induced changes in myocardial function and the underlying mechanism
      involved, with a focus on autophagy. Cold exposure (4 degrees C for 3 wk)
      promoted oxidative stress and protein damage, increased left ventricular end
      systolic and -diastolic diameter, and suppressed fractional shortening and whole
      heart contractility, the effects of which were significantly attenuated or
      ablated by metallothionein. Levels of the autophagy markers LC3B-II, beclin-1,
      and Atg7 were significantly upregulated with unchanged autophagy adaptor protein
      p62. Fluorescent immunohistochemistry revealed abundant LC3B puncta in cold
      temperature-exposed mouse hearts. Coimmunoprecipitation revealed increased
      dissociation between Bcl2 and Beclin-1. Cold exposure reduced phosphorylation of
      the autophagy inhibitory signaling molecules Akt and mTOR, increased ULK1
      phosphorylation, and dampened eNOS phosphorylation (without changes in their
      total protein expression). These cold exposure-induced changes in myocardial
      function, autophagy, and autophagy signaling cascades were significantly
      alleviated or mitigated by metallothionein. Inhibition of autophagy using 3
      methyladenine in vivo reversed cold exposure-induced cardiomyocyte contractile
      defects. Cold exposure-induced cardiomyocyte dysfunction was attenuated by the
      antioxidant N-acetylcysteine and the lysosomal inhibitor bafilomycin A1.
      Collectively, these findings suggest that metallothionein protects against cold
      exposure-induced cardiac anomalies possibly through attenuation of cardiac
      autophagy.

PMID- 23132297
TI  - Potential role for Nrf2 activation in the therapeutic effect of MG132 on diabetic
      nephropathy in OVE26 diabetic mice.
AB  - Oxidative stress is a major cause of diabetic nephropathy. Upregulation of the
      key antioxidative transcription factor, nuclear factor-erythroid 2-related factor
      2 (Nrf2), was found to prevent the development of diabetic nephropathy. The
      present study was designed to explore the therapeutic effect of Nrf2 induced by
      proteasomal inhibitor MG132 at a low dose (10 MUg/kg) on diabetic nephropathy.
      Transgenic type 1 diabetic (OVE26) mice displayed renal dysfunction with
      albuminuria by 3 mo of age, at which time MG132 treatment was started. After 3-mo
      treatment with MG132, renal function, morphology, and biochemical changes were
      examined with real-time PCR, Western blotting, and immunohistochemical
      examination. Compared with age-matched, nontreated diabetic mice, MG132-treated
      diabetic mice showed significant improvements in terms of renal structural and
      functional alterations. These therapeutic effects were associated with increased
      Nrf2 expression and transcriptional upregulation of Nrf2-regulated antioxidants.
      Mechanistic study using human renal tubular HK11 cells confirmed the role of
      Nrf2, as silencing the Nrf2 gene with its specific siRNA abolished MG132
      prevention of high-glucose-induced profibrotic response. Furthermore, diabetes
      was found to significantly increase proteasomal activity in the kidney, an effect
      that was significantly attenuated by 3 mo of treatment with MG132. These results
      suggest that MG132 upregulates Nrf2 function via inhibition of diabetes-increased
      proteasomal activity, which can provide the basis for the therapeutic effect of
      MG132 on the kidney against diabetes-induced oxidative damage, inflammation,
      fibrosis, and eventual dysfunction.

PMID- 23132298
TI  - Delivery of adiponectin gene to skeletal muscle using ultrasound targeted
      microbubbles improves insulin sensitivity and whole body glucose homeostasis.
AB  - Numerous studies have shown that adiponectin confers antidiabetic effects via
      both insulin-like and insulin-sensitizing actions. The majority of adiponectin in
      circulation is derived from adipocytes; however, other tissues such as skeletal
      muscle can produce adiponectin. This study was designed to investigate the
      functional significance of adiponectin produced by skeletal muscle. We
      encapsulated the adiponectin gene in lipid-coated microspheres filled with
      octafluoropropane gas that were injected into the systemic circulation and
      destroyed within the microvasculature of skeletal muscle using ultrasound. We
      first demonstrated safe and successful targeting of luciferase and green
      fluorescent protein reporter genes to skeletal muscle using this approach and
      then confirmed efficient overexpression of adiponectin mRNA and oligomeric
      protein forms. Glucose tolerance test indicated that overexpression of
      adiponectin in skeletal muscle was able to improve glucose intolerance induced by
      feeding mice a high-fat diet (HFD), and this correlated with improved skeletal
      muscle insulin signaling. We then performed hyperinsulinemic-euglycemic clamp
      studies and demonstrated that adiponectin overexpression attenuated the decreases
      in glucose infusion rate, glucose disposal, and increase in glucose appearance
      induced by HFD. Ultrasound-targeted microbubble destruction (UTMD) delivery of
      adiponectin to skeletal muscle also enhanced serum adiponectin levels and
      improved hepatic insulin sensitivity. In conclusion, our data show that UTMD
      efficiently delivers adiponectin to skeletal muscle and that this improves
      insulin sensitivity and glucose homeostasis.

PMID- 23132300
TI  - A complex picture of associations between two host mussels and symbiotic bacteria
      in the Northeast Atlantic.
AB  - Among chemosymbiotic metazoans found at deep-sea hydrothermal vents, cold seeps
      and organic falls, members of the mussel clade Bathymodiolinae (Bivalvia:
      Mytilidae) have evolved interactions with a higher diversity of bacterial
      lineages than other bivalve groups. Here, we characterized the bacteria
      associated with "Bathymodiolus" mauritanicus and Idas-like specimens from three
      sites in the Northeast Atlantic (two mud volcanoes in the Gulf of Cadiz and one
      seamount of the Gorringe Bank). Phylogenetic analysis of bacterial 16S rRNA
      encoding gene sequences demonstrated that "B". mauritanicus has a dual symbiosis
      dominated by two phylotypes of methane-oxidising bacteria and a less abundant
      phylotype of a sulphur-oxidising bacterium. The latter was the dominant phylotype
      in a sympatric population of Idas-like mussels at the Darwin mud volcano. These
      results are the first report of a bacterial phylotype shared between two deep-sea
      mussels from divergent clades. This sulphur-oxidising bacterium was absent from
      Idas-like specimens from the other two sites (Gorringe Bank and Meknes mud
      volcano), in which bacterial clone libraries were dominated by other
      Gammaproteobacteria related to symbionts previously identified in Idas
      modiolaeformis from the Eastern Mediterranean. All Idas-like specimens studied
      herein are closely related and also related to I. modiolaeformis. However, they
      probably display different associations with bacteria, with the possible absence
      of both methane- and sulphur-oxidising symbionts at the Gorringe Bank. These
      results draw a very complex picture of associations between mussels and bacteria
      in the Northeast Atlantic, which could be highly variable depending on locale
      characteristics of the habitats.

PMID- 23132299
TI  - Psychiatric comorbidities of episodic and chronic migraine.
AB  - Migraine is a prevalent disabling neurological disorder associated with a wide
      range of medical and psychiatric comorbidities. Population- and clinic-based
      studies suggest that psychiatric comorbidities, particularly mood and anxiety
      disorders, are more common among persons with chronic migraine than among those
      with episodic migraine. Additional studies suggest that psychiatric comorbidities
      may be a risk factor for migraine chronification (i.e., progression from episodic
      to chronic migraine). It is important to identify and appropriately treat
      comorbid psychiatric conditions in persons with migraine, as these conditions may
      contribute to increased migraine-related disability and impact, diminished health
      related quality of life, and poor treatment outcomes. Here, we review the current
      literature on the rates of several psychiatric comorbidities, including
      depression, anxiety, and post-traumatic stress disorder, among persons with
      migraine in clinic- and population-based studies. We also review the link between
      physical, emotional, and substance abuse, psychiatric disorders, and migraine.
      Finally, we review the data on psychiatric risk factors for migraine
      chronification and explore theories and evidence underlying the comorbidity
      between migraine and these psychiatric disorders. 

PMID- 23132301
TI  - A correlation for 1,9-decadiene/water partition coefficients.
AB  - An important series of papers by Xiang, Anderson, and coworkers has established
      the strong correlation between phospholipid bilayer membrane permeability and the
      1,9-decadiene/water partition coefficient over a wide range of compounds,
      elevating the importance of K(decadiene/w) as a predictor of molecular
      bioavailability. On the basis of a 58-point dataset developed by these authors,
      this research note develops an optimal correlation predicting log(10)
      K(decadiene/w) in terms of the octanol/water partition coefficient and four of
      the Abraham solvation parameters, namely A (hydrogen bond acidity), S
      (polarity/polarizability), E (excess molar refraction), and V (McGowan
      characteristic volume). The fitted dataset is described to within a root-mean
      square error of 0.42, and the probable error in making a prediction for a
      compound not present therein is 0.49. It is shown that this correlation error for
      K(decadiene/w) is the dominant source of uncertainty in applying a comprehensive
      new model of phospholipid bilayer membrane permeability developed in a companion
      paper (Nitsche and Kasting, submitted for publication), which superposes the
      effects of molecular size and lipid density upon the decadiene lipophilicity
      scale. Thus, more experimental studies to augment the limited existing database
      on K(decadiene/w) are called for.

PMID- 23132302
TI  - Increasing the flexoelastic ratio of liquid crystals using highly fluorinated
      ester-linked bimesogens.
AB  - We present experimental results on the bulk flexoelectric coefficients e and
      effective elastic coefficients K of non-symmetric bimesogenic liquid crystals
      when the number of terminal and lateral fluoro substituents is increased. These
      coefficients are of importance because the flexoelastic ratio e/K governs the
      magnitude of flexoelectro-optic switching in chiral nematic liquid crystals. The
      study is carried out for two different types of linkage in the flexible spacer
      chain that connects the separate mesogenic units: these are either an ether or an
      ester unit. It is found that increasing the number of fluorine atoms on the
      mesogenic units typically leads to a small increase in e and a decrease in K,
      resulting in an enhancement of e/K. The most dramatic increase in e/K, however,
      is observed when the linking group is changed from ether to ester units, which
      can largely be attributed to an increase in e. Increasing the number of fluorine
      atoms does, however, increase the viscoelastic ratio and therefore leads to a
      concomitant increase in the response time. This is observed for both types of
      linkage, although the ester-linked compounds exhibit smaller viscoelastic ratios
      compared with their ether-linked counterparts. Highly fluorinated ester-linked
      compounds are also found to exhibit lower transition temperatures and dielectric
      anisotropies. As a result, these compounds are promising materials for use in
      electro-optic devices.

PMID- 23132304
TI  - Luminometric sub-nanoliter droplet-to-droplet array (LUMDA) and its application
      to drug screening by phase I metabolism enzymes.
AB  - Here we show the fabrication of the Luminometric Sub-nanoliter Droplet-to-droplet
      Array (LUMDA chip) by inkjet printing. The chip is easy to be implemented and
      allows for a multiplexed multi-step biochemical assay in sub-nanoliter liquid
      spots. This concept is here applied to the integral membrane enzyme CYP3A4, i.e.
      the most relevant enzymatic target for phase I drug metabolism, and to some
      structurally-related inhibitors.

PMID- 23132305
TI  - The effects of vitamin A compounds on hyaluronic acid released from cultured
      rabbit corneal epithelial cells and keratocytes.
AB  - A role of vitamin A in the synthesis of hyaluronic acid by skin cells is well
      known. Hyaluronic acid is produced by corneal epithelial cells and keratocytes in
      the eye. We investigated whether rabbit corneal epithelial cells and keratocytes
      release hyaluronic acid after exposure to vitamin A compounds. Rabbit corneal
      epithelial cells and keratocytes were inoculated with RCGM2 medium and incubated
      at 37oC under 5% CO(2) in air for 24 h. The medium was then replaced with medium
      containing 0.1, 1, 10, or 100 MUM retinoic acid or retinol palmitate (VApal) and
      incubated for another 48 h. Hyaluronic acid release from both corneal epithelial
      cells and keratocytes during culture was increased by retinoic acid at the lower
      concentration of 0.1 MUM and 1 MUM determined with a sandwich binding protein
      assay kit. However, it was significantly decreased at the higher concentrations
      of 10 MUM and 100 MUM, and the cell count determined with a Neutral Red assay kit
      was also decreased at these concentrations. On the other hand, hyaluronic acid
      release from corneal epithelial cells during culture was increased by VApal at
      the lower concentration of 0.1 MUM and 1 MUM, but there was no significant
      difference in the cell count for either corneal epithelial cells or keratocytes
      in the presence of VApal at any concentration. In conclusion, it is suggested
      that vitamin A stimulates the release of hyaluronic acid from cultured rabbit
      corneal epithelial cells and keratocytes.

PMID- 23132306
TI  - The interactive effect of dietary water-soluble vitamin levels on the depression
      of gonadal development in growing male rats kept under disturbed daily rhythm.
AB  - The purpose of this study was to clarify the effects of nutrients on the gonadal
      development of male rats kept under constant darkness as a model of disturbed
      daily rhythm. In the present study we examined the effects of nine water-soluble
      vitamins. We selected 7 water-soluble vitamins (choline, nicotinic acid (NA),
      pantothenic acid (PA), vitamin B6 (VB6), vitamin B1 (VB1), vitamin B2 (VB2) and
      folic acid (FA)) as experimental factors for the first experiment (Ex. 1) and
      biotin and vitamin B12 (VB12) as experimental factors for the second experiment
      (Ex. 2). The dietary content of these vitamins was normal or six times the normal
      content. Lighting condition (L.C.) was also added as a factor. Four-week-old male
      rats (Fischer 344 strain) were kept under constant darkness or normal lighting
      (12-h light/dark cycle) for 4 wk. The depression of gonadal development in the
      constant darkness groups (D-groups) was shown. The L.C., PA, VB6 and VB1
      influenced testes development, and these three vitamins had interactions with
      L.C. Among the normal lighting groups (N-groups), the highest value for testes
      weight was observed under the normal-PA, high-VB6 and high-B1 diet; on the other
      hand, among the D-groups, it was observed under the high-PA, normal-VB6 and
      normal-VB1 diet. The results showed that the depression of gonadal development in
      rats kept under disturbed daily rhythm was improved by getting a high amount of
      PA and normal amount of VB6 and VB1.

PMID- 23132307
TI  - Effect of different intake levels of dietary protein and physical exercise on
      bone mineral density and bone strength in growing male rats.
AB  - Having higher bone mineral density (BMD) during growth is complexly influenced by
      many factors. For example, nutrition and physical exercise are key factors.
      However, few studies have investigated the combined effects of these factors. In
      this study, we investigated the effect of physical exercise and different levels
      of protein intake on BMD and bone strength of growing male rats. Forty-seven male
      Wistar rats (5 wk old) were randomized into 10% (Low), 20% (Moderate) and 40%
      (High) protein diet groups, and each group was further divided into exercise
      groups (LEx, MEx, HEx) or non-exercise groups (L, M, H). Exercise group rats were
      trained 6 d per week on a treadmill (25-30 m/min, 60 min) for 60 d. After being
      sacrificed, their BMD and bone strength were evaluated. The BMD of tibia, femoral
      breaking force and energy were significantly lower in the low protein diet groups
      than the other diet groups. In particular, the femoral breaking energy was
      significantly lower in the HEx group than in the H group, while there were no
      differences between LEx and L or MEx and M. Taken together, our data suggests
      that a low protein intake could suppress acquisition of bone mass and increasing
      bone strength during growth. Moreover, a high protein intake could also suppress
      bone strength during growth in which physical activity was vigorously performed.
      Therefore, sustaining an adequate protein intake level, around 20% protein
      intake, may be of significance for increasing not only bone mass but bone
      strength during growth.

PMID- 23132308
TI  - Self-reported rate of eating and risk of overweight in Japanese children: Ryukyus
      Child Health Study.
AB  - The possible role of eating rate in promoting obesity has long been of interest.
      We examined the association between rate of eating and overweight status in
      Japanese children and adolescents. This Japanese cross-sectional study included
      15,974 children (6-11 y; 7,956 boys and 8,018 girls) and 8,202 adolescents (12-15
      y; 3,944 boys and 4,258 girls). Rate of eating was self-reported according to
      five categories. Body mass index (BMI) was calculated from self-reported body
      weight and height. Overweight was defined according to the International Obesity
      Task Force age- and sex-specific BMI cutoffs. The overall prevalence of
      overweight was 13.2%. Rate of eating was positively associated with the risk of
      overweight, independent of protein, fat, and dietary fiber intakes. Multivariate
      odds ratios (95% confidence intervals) for overweight in the very slow,
      relatively slow, medium, relatively fast, and very fast categories were 0.31
      (0.20, 0.49), 0.49 (0.40, 0.60), 1 (reference), 2.81 (2.42, 3.26), and 4.49
      (3.47, 5.81) in male children; 0.42 (0.31, 0.58), 0.49 (0.41, 0.59), 1
      (reference), 2.74 (2.27, 3.31), and 5.69 (3.75, 8.63) in female children; 0.13
      (0.03, 0.54), 0.43 (0.28, 0.65), 1 (reference), 2.31 (1.88, 2.84), and 3.84
      (2.77, 5.31) in male adolescents; and 0.55 (0.30, 1.01), 0.46 (0.33, 0.65), 1
      (reference), 1.30 (0.99, 1.71), and 1.49 (0.84, 2.65) in female adolescents,
      respectively (all p for trend<0.0001). In conclusion, this large cross-sectional
      study in Japan showed that a higher rate of eating was independently positively
      associated with an increasing risk of overweight in children and adolescents.

PMID- 23132309
TI  - Characteristics of under- and over-reporters of energy intake among young
      Japanese women.
AB  - Evidence on factors associated with misreporting of energy intake is limited,
      particularly in non-Western populations. We examined the characteristics of under
      and over-reporters of energy intake in young Japanese women. Subjects were 3,956
      female Japanese dietetic students aged 18-20 y (mean body mass index: 20.9
      kg/m(2)). Energy intake was assessed using a comprehensive self-administered diet
      history questionnaire. Estimated energy requirement was calculated based on self
      reported information on age, body height and weight, and physical activity with
      the use of an equation from the US Dietary Reference Intakes. Under-, acceptable,
      and over-reporters of energy intake were identified based on the ratio of energy
      intake to estimated energy requirement, according to whether the individual's
      ratio was below, within, or above the 95% confidence limits of the expected ratio
      of 1.0 (<0.70, 0.70-1.30, and >1.30, respectively). Risk of being an under- or
      over-reporter of energy intake compared to an acceptable reporter was analyzed
      using multiple logistic regression. The percentage of under-, acceptable, and
      over-reporters of energy intake was 18.4, 73.1, and 8.4%, respectively. Under
      reporting was associated with overweight or obesity, perception that one's own
      weight was too heavy or light, lower dietary consciousness, active lifestyle,
      living without family, and living in a city (compared with a metropolitan area).
      Over-reporting was associated with sedentary lifestyle only. This study of lean
      young Japanese women showed that energy intake misreporting, particularly under
      reporting, was common and differential among populations. Particularly, perceived
      weight status was associated with under-reporting of energy intake, independent
      of actual weight status.

PMID- 23132303
TI  - The complexity of prostate cancer: genomic alterations and heterogeneity.
AB  - Although prostate cancer is the most common malignancy to affect men in the
      Western world, the molecular mechanisms underlying its development and
      progression remain poorly understood. Like all cancers, prostate cancer is a
      genetic disease that is characterized by multiple genomic alterations, including
      point mutations, microsatellite variations, and chromosomal alterations such as
      translocations, insertions, duplications, and deletions. In prostate cancer, but
      not other carcinomas, these chromosome alterations result in a high frequency of
      gene fusion events. The development and application of novel high-resolution
      technologies has significantly accelerated the detection of genomic alterations,
      revealing the complex nature and heterogeneity of the disease. The clinical
      heterogeneity of prostate cancer can be partly explained by this underlying
      genetic heterogeneity, which has been observed between patients from different
      geographical and ethnic populations, different individuals within these
      populations, different tumour foci within the same patient, and different cells
      within the same tumour focus. The highly heterogeneous nature of prostate cancer
      provides a real challenge for clinical disease management and a detailed
      understanding of the genetic alterations in all cells, including small
      subpopulations, would be highly advantageous.

PMID- 23132310
TI  - Search for promotion factors of ultrasound bone measurement in Japanese males and
      pre/post-menarcheal females aged 8-14 years.
AB  - There is little evidence regarding the associations between bone growth and
      environmental factors among growing children, especially in Asians. The aim of
      this cross-sectional study was to search for the promotion factors of bone growth
      in Japanese children during growth. The study subjects were male (n=333) and
      pre/post-menarcheal female (n=179/n=68) school children aged 8-14 y. Bone status
      at the calcaneus was evaluated by quantitative ultrasound (Benus III), and the
      bone area ratio (BAR) was used as an evaluation index. Dietary intakes were
      assessed via brief self-administered diet history questionnaires. The
      participants were asked to record all of their activities for 3 d (2 weekdays and
      1 holiday). They were also required to provide the most recent anthropometric
      measurement records at their schools and answer questions about the frequency of
      fractures and, for females, the length of time since menarche. Multiple
      regression analysis with dummy variables demonstrated that age, magnesium (more
      than the RDA), vitamin B(1) (more than the RDA), mean physical activity intensity
      per day (more than 1.7 METs), vitamin C (more than the RDA) and calcium (more
      than the RDA) were significantly positive influential factors of BAR for males.
      For premenarcheal females, age, vitamin A (more than the RDA), BMI, and mean
      physical activity intensity per day (more than 1.7 METs) were significantly
      positive influential factors of BAR, and for postmenarcheal females, only BMI and
      age were significantly positive influential factors of BAR. The results suggest
      that several manageable factors correlate with the bone mass, and the
      associations differ depending on gender and menarcheal status.

PMID- 23132311
TI  - Anti-allergic properties of a matured fruit extract of the date palm tree
      (Phoenix dactylifera L.) in mite-sensitized mice.
AB  - The effects of oral ingestion of a hot water extract of matured fruit of the date
      palm tree (Phoenix dactylifera L.) on allergic responses were investigated in
      mite-sensitized mice. Sneezing and nose rubbing events in mice given a date
      extract-added diet were significantly lower than in those given an extract-free
      (control) diet. The serum total and mite antigen-specific immunoglobulin (Ig) E
      levels, and the number of spleen interleukin-4(+)CD4(+), IgE(+)B220(+) and
      FcepsilonRIalpha(+)CD117(+) cells was significantly lower in mice given the date
      extract-added diet than in those given the control diet. Chlorogenic acid,
      pelargonin and ferulic acid significantly reduced the number of IgE(+)B220(+)
      cells, while chlorogenic acid and pelargonin significantly decreased the number
      of FcepsilonRIalpha(+)CD117(+) cells in mouse spleen cell cultures. These results
      suggest that some polyphenols in the date may reduce mite-induced allergic
      symptoms in mice via a decrease in the number of IgE-producing plasma cells and
      high-affinity IgE receptor-expressing mast cells.

PMID- 23132312
TI  - Analysis and functionality of major polyphenolic components of Polygonum
      cuspidatum (itadori).
AB  - Polygonum cuspidatum has been broadly utilized as a herbal medicine in Asia, but
      the outline of the polyphenol compounds in the plant has not been characterized
      well. In the present study, the major polyphenolic components were isolated from
      the roots of P. cuspidatum, and identified as resveratrol and its glucosides,
      resveratroloside and polydatin. On the other hand, chlorogenic acid was found to
      be one of the polyphenolic components in the leaves and stems of the plant. Next,
      we elucidated that resveratrol derivatives and chlorogenic acid exhibit alpha
      glucosidase inhibitory activities, and resveratroloside exhibits the same
      inhibitory activity as quercetin does. Furthermore, DPPH radical scavenging
      activities of antioxidants including resveratrol derivatives and chlorogenic acid
      derivatives were examined by initial rate analyses of their reactions.
      Subsequently, it was revealed that resveratrol derivatives have slow-acting
      effects on the radical scavenging activity and that chlorogenic acid derivatives
      exhibit very fast-acting effects.

PMID- 23132313
TI  - Short-chain fatty acids increase the level of calbindin-D9k messenger RNA in Caco
      2 cells.
AB  - Fructooligosaccharides (FOS) are indigestible oligosaccharides that increase the
      expression of calbindin-D9k and consequently increase calcium absorption by the
      colon in rats. The molecular mechanism of the increased expression of calbindin
      D9k resulting from FOS ingestion has not been elucidated. Short-chain fatty acids
      (SCFAs), namely, fermentation products of FOS by intestinal bacteria have been
      hypothesized as direct effectors of calbindin-D9k gene expression. To test this
      hypothesis, SCFAs were added to Caco-2 human intestinal epithelial cells, and
      changes in the levels of transcription of genes for calbindin-D9k, and
      transcription factors (vitamin D receptor: VDR, caudal homeobox-2: Cdx-2,
      hepatocyte nuclear factor 1-alpha: HNF1-alpha) were determined by quantitative
      reverse transcription polymerase chain reaction. Addition of sodium propionate or
      sodium butyrate to cell cultures increased levels of calbindin-D9k mRNA to 731%
      (p<0.05) and 321% (p<0.05), respectively. However, addition of these SCFAs did
      not affect the levels of mRNA VDR, Cdx-2, or HNF1-alpha. In conclusion, addition
      of SCFAs to cultured Caco-2 cells results in elevation of calbindin-D9k mRNA,
      consistent with the expected role of SCFAs as mediators of the increase of
      calcium absorption in rats that were fed with FOS.

PMID- 23132314
TI  - Diallyl disulfide reduced dose-dependently the number of lymphocyte subsets and
      monocytes in rats.
AB  - Diallyl disulfide (DADS) is a major sulfur compound of garlic, and exerts anti
      inflammatory, immune-modulatory, and enhancing sympathetic activity effects.
      However, it still remains unclear how DADS affects the distribution of white
      blood cell subsets, which is essential to execute effective immune responses and
      partially regulated by adrenal glucocorticoids. Therefore, we examined the dose
      dependent effects of DADS administration on the circulating number of white blood
      cells (WBCs) and lymphocyte subsets, and plasma corticosterone concentration in
      rats. Male 10-wk-old Sprague Dawley rats were divided into the DADS-free and DADS
      orally administered (dose=10, 20, and 40 mg/kg BW) groups. Blood samples were
      collected from the tail vein at 0, 1, 2, 4, and 6 h after the administration.
      DADS administration decreased dose- and time-dependently the circulating number
      of total WBCs, total lymphocytes, and monocytes. Within the lymphocyte subsets,
      the circulating number of T-lymphocytes and B-lymphocytes was significantly
      reduced 4 h after DADS administration in a dose-dependent manner, although that
      of natural killer (NK) cells was not affected. On the other hand, although DADS
      administration did not significantly change the circulating number of
      neutrophils, the circulating number of eosinophils and basophils showed a
      decreasing tendency after DADS administration. In contrast, plasma corticosterone
      concentration was increased 2 h after DADS administration in a dose-dependent
      manner. These results suggest that DADS administration reduces the circulating
      number of monocytes and lymphocytes, including especially acquired immune cells,
      via the action of corticosterone, and the effects are induced in a dose-dependent
      manner.

PMID- 23132315
TI  - Dietary ornithine affects the tissue protein synthesis rate in young rats.
AB  - The purpose of this study was to determine whether ornithine affects the rate of
      tissue protein synthesis in male rats. Two experiments were done on five or two
      groups of young rats (5 wk) given diets containing 0.15, 0.3, 0.5 or 0.7%
      ornithine-HCl added to a 20% casein diet for 1 d (only one 3 h period)
      (Experiment 1), and given a diet containing 0 or 0.7% ornithine-HCl added to a
      20% casein diet for 10 d (Experiment 2). The plasma concentration of growth
      hormone (GH) was the highest in rats fed 0.5 and 0.7% ornithine added to the 20%
      casein diet. The fractional rates of protein synthesis in brain regions, liver
      and gastrocnemius muscle increased significantly with the 20% casein+0.7%
      ornithine diet compared with the 20% casein diet. In brain regions, liver and
      gastrocnemius muscle, the RNA activity [g protein synthesized/(g RNA.d)]
      significantly correlated with the fractional rate of protein synthesis. The RNA
      concentration (mg RNA/g protein) was not related to the fractional rate of
      protein synthesis in any organ. The present results suggest that the treatment of
      young rats with ornithine is likely to increase the concentration of plasma GH
      and the rate of protein synthesis in the tissues, and that RNA activity is at
      least partly related to the fractional rate of tissue protein synthesis.

PMID- 23132316
TI  - Inhibitory effects of wasabi isothiocyanates on chemical mediator release in RBL
      2H3 rat basophilic leukemia cells.
AB  - Wasabi is a plant of Japanese origin. It belongs to the family Brassicaceae and
      produces various isothiocyanates (ITCs). To clarify the type I allergies
      inhibited by wasabi ITCs, we investigated the inhibitory effect on chemical
      mediator release from dinitrophenylated bovine serum albumin (DNP-BSA)-stimulated
      RBL-2H3 rat basophilic leukemia cells. Allyl ITC (AITC), sec-butyl ITC (s-BuITC),
      and 3-butenyl ITC (3-BuITC), which have 3 or 4 carbon chains, inhibited histamine
      release but did not inhibit the release of leukotriene B4 (LTB4) or cysteinyl LTs
      (CysLTs). 4-Pentenyl ITC (4-PeITC) and 5-hexenyl ITC (5-HeITC), which have 5 or 6
      carbon chains and an unsaturated bond at the end, inhibited LTB4 release but did
      not inhibit the release of histamine or CysLTs. 6-Methylthiohexyl ITC (6-MTITC),
      6-methylsulfinylhexyl ITC (6-MSITC), and 6-methylsulfonylhexyl ITC (6-MSFITC),
      which have a sulfur atom inserted at the end of a 6-carbon chain, inhibited the
      release of histamine, LTB4, and CysLTs and the elevation in intracellular Ca(2+).
      These results suggest that wasabi ITCs inhibited type I allergies by inhibiting
      chemical mediator release and that the inhibitory effects on each chemical
      mediator were due to differences in the side chain structure of the wasabi ITCs.

PMID- 23132317
TI  - [PleurX drainage catheter for palliative treatment of malignant pleural
      effusion].
AB  - OBJECTIVE: In patients with malignant effusions and ECOG 3 - 4 or unexpandable
      lung, the PleurX(r) catheter system provides an effective at-home palliation of
      symptoms associated with recurrent pleural effusions. We investigated the
      clinical results of patients treated by this method in our population. METHODS:
      All patients treated with PleurX between June 2005 and September 2010 in our
      clinical center were recorded using a predefined data sheet. Primary points of
      interest were complications associated with the insertion procedure, short- and
      long-term complications after insertion of the catheter, the rate of pleurodesis,
      the frequency of hospitalizations due to effusion-associated symptoms, time of
      drainage and survival time after insertion. In order to assess follow-up, a
      standardized questionnaire was sent to the attending practitioners. RESULTS:
      Pleural effusions were most frequently due to lung cancer, breast cancer and
      mesothelioma. The rate of compilations associated with the insertion procedure
      was 7 %, and complications could easily be managed. The rate of short-term
      complications after insertion of the catheter was 7 %, and of long-term
      compilations 18 %. The rate of pleurodesis was 16 %. 78 % of patients did not
      need another hospitalization due to effusion-related symptoms. The mean time of
      drainage was 52 days. The mean survival after insertion of the drainage was 76 +/
      85 days (1 - 453). CONCLUSIONS: The insertion of a PleurX catheter is associated
      with a low complication rate. Short-term and long-term complications are usually
      mild and can be readily managed. Hospitalizations due to effusion-related
      symptoms were not necessary in the majority of patients.

PMID- 23132318
TI  - [Use of a lung function screening device for identifying patients at risk for
      COPD in general practice].
AB  - BACKGROUND: Screening measures can facilitate the diagnosis of chronic
      obstructive pulmonary disease (COPD) and help save costs and time. We examined
      whether use of a lung function screener (Vitalograph copd-6TM) can help general
      practitioners to identify patients at risk for COPD. METHODS: In 17,856 patients
      aged > 40 years (smokers/ex-smokers with cough and/or exertional dyspnoea)
      general practitioners measured prebronchodilator FEV1 [% of predicted] and
      FEV1/FEV6 with the lung function screening device. In addition, the general
      practitioners completed a questionnaire on symptoms, history and planned measures
      and estimated whether or not the patient was at risk for COPD. RESULTS: In 2927
      patients (16.7 %) an FEV1/FEV6 < 70 % was measured; 88.2 % of these were classed
      by the doctors as being at risk for COPD. The total number of all patients with
      suspected COPD was considerably greater (10,000; 56 % of the total population);
      in only 25.3 % was an FEV1/FEV6 < 70 % documented. Compared with patients without
      a suspicion of COPD, patients judged to be at risk for COPD in spite of an
      FEV1/FEV6 >= 70 % were more often male, had more cigarette pack years and more
      often had dyspnoea, but less often cough, as main symptom. They had more
      concomitant diseases and previous hospitalisations, more prescriptions for
      bronchodilators, glucocorticoids and antibiotics in the past year and lower FEV1
      values. In 61.3 % of the patients with suspected COPD the general practitioners
      planned further evaluation by spirometry, in 39.9 % referral to a pulmonologist
      as alternative or additional procedures were suggested. CONCLUSION: Most patients
      with an FEV1/FEV6 < 70 % measured with the lung function screener Vitalograph
      copd-6TM were classed by the general practitioners as being at risk for COPD.
      Even in patients with unremarkable FEV1/FEV6 values the diagnosis of suspected
      COPD was often made if clinical signs or symptoms or a reduced FEV1 pointed to
      such a suspicion.

PMID- 23132319
TI  - [Mechanisms of cardiovascular co-morbidity in patients with obstructive sleep
      apnoea syndrome].
AB  - The repetitive intermittent hypoxic episodes, central nervous arousal and
      intrathoracic pressure fluctuations that occur together with obstructive sleep
      apnoea are the primary pathophysiological mechanisms responsible for the
      cardiovascular co-morbidity. These phenomena lead to increased oxidative stress,
      systemic inflammation, disrupted vasomotor function, increased sympathetic
      activity and the development of arteriosclerosis in blood vessels. CPAP therapy
      lowers arterial blood pressure and has a positive effect on relevant specific
      aspects of cardiovascular co-morbidity. Until the results of current randomised
      studies have been published, it has to be decided on an individual basis whether
      the cardiovascular situation alone justifies CPAP therapy. This will usually be
      the case in severe OSA with daytime sleepiness, in young patients and patients
      with good compliance. Interventions that reduce cardiovascular risk and also have
      a positive effect on OSA, i. e., weight reduction, physical exercise and smoking
      cessation are always appropriate.

PMID- 23132320
TI  - [My memories of the tuberculosis Stapelburg Hospital].

PMID- 23132322
TI  - Rehabilitation:  advanced but not translated.

PMID- 23132321
TI  - Pathophysiology of prediabetes and treatment implications for the prevention of
      type 2 diabetes mellitus.
AB  - Type 2 diabetes and other non-communicable diseases (NCD) are a growing public
      health challenge globally. An estimated 285 million people, corresponding to 6.4
      % of the world's adult population has diabetes. This is expected to reach 552
      million by 2030, 7.8 % of the adult population, with the African region expected
      to experience the greatest increase. A much larger segment of the world's
      population, approximating 79 million individuals in the US alone, has
      prediabetes. Multiple factors including genetic predisposition, insulin
      resistance, increased insulin secretory demand, glucotoxicity, lipotoxicity,
      impaired incretin release/action, amylin accumulation, and decreased beta-cell
      mass play a causative role in the progressive beta-cell dysfunction
      characteristic of prediabetes. Interventions preventing progression to type 2
      diabetes should therefore delay or prevent beta-cell failure. This article will
      first review the principal pathophysiological mechanisms underlying prediabetes
      and subsequently address treatment considerations based on these in the
      prevention of type 2 diabetes. In view of long-standing safety data with
      demonstrated efficacy and cost-effectiveness in the prevention of type 2 diabetes
      in high-risk individuals, metformin should be considered as initial therapy for
      those unable to comply with or lifestyle modification or where the latter has
      been ineffective in decreasing progression to type 2 diabetes.

PMID- 23132323
TI  - Polypropylene mesh repair of incarcerated and strangulated hernias: a prospective
      clinical study.
AB  - PURPOSE: There is a common doubt regarding the application of polypropylene mesh
      to treat incarcerated and strangulated hernias due to the possibility of surgical
      site infection. We aimed to investigate the results of mesh repair of
      incarcerated and strangulated hernias, and to evaluate the incidence of wound
      infection and recurrence. METHODS: One hundred and fifty-three consecutive
      patients with incarcerated and strangulated hernias underwent surgery with mesh
      repair. The patients were divided into two groups: a resection group and a
      nonresection group. Fisher's exact test, the Chi-square test and independent
      samples t test were used to determine the statistical significance level (p <
      0.05). RESULTS: While 53 patients required organ resection, the remaining 100
      patients did not. The most frequently incarcerated organs were the omentum (86),
      small bowel (74) and colon (15). Most of the resections were performed in the
      omentum (36), small bowel (23) and colon (2). While five of the 53 patients
      (9.4%) in the resection group developed wound infections, no infections were
      observed in the nonresection group (p = 0.004). The infection rate in all
      patients was 3.3% (five of 153 patients). None of the infected patients required
      mesh removal. There were no mortalities or recurrence in either group.
      CONCLUSIONS: The findings revealed effective and safe usage of mesh along with
      antibiotic therapy in patients undergoing incarcerated and strangulated hernia
      repair.

PMID- 23132324
TI  - Warren shunt combined with partial splenectomy for children with extrahepatic
      portal hypertension, massive splenomegaly, and severe hypersplenism.
AB  - PURPOSE: To establish the importance of shunt surgery combined with partial
      resection of the spleen for selected pediatric patients with extra-hepatic portal
      vein obstruction (EHPVO), enormous splenomegaly and severe hypersplenism. Severe
      hypersplenism is often refractory to treatment with endoscopic sclerotherapy or
      band ligation and shunt surgery; however, to our knowledge, this is the first
      such study to be published. METHODS: Distal splenorenal shunt with partial
      resection of the spleen was performed in 16 of 60 children treated for EHPVO in
      the Gastroenterology Department of our hospital. Upper gastrointestinal endoscopy
      had shown esophageal varices of varying grade in all patients and band ligation
      or endoscopic sclerotherapy had been done for children with a history of
      bleeding. The indications for surgery were pain and discomfort caused by a large
      spleen (5-15 cm below the costal margin) and symptomatic hypersplenism with
      leucopenia, thrombocytopenia, and anemia. Partial resection of the spleen was
      performed, starting with ligation of the branches and tributaries of the caudal
      two-thirds. When an ischemic line demarcated the splenic parenchyma, it was
      transected using electrocautery or LigaSure, leaving 20-30 % of splenic tissue.
      After the spleen resection, a Warren shunt was performed. Platelet and white
      blood cell counts and liver function tests were performed before and after the
      operation. Growth was assessed using SD scores (z scores) for height, weight, and
      body mass index at the time of surgery and 1 year later. RESULTS: Postoperative
      recovery was uneventful and the leukocyte and platelet counts normalized. The
      shunt patency rate was 100 %. Two cases of shunt stenosis were treated
      successfully with percutaneous angioplasty. There was no postoperative mortality.
      During the follow-up period, from 1 to 7 years, all 16 children were
      asymptomatic, with improved quality of life, growth, and nutrition. No episodes
      of variceal bleeding, sepsis or encephalopathy occurred. CONCLUSION: Our results
      demonstrate that shunt surgery with partial resection of the spleen is effective
      and safe for pediatric patients with massive splenomegaly and severe
      hypersplenism secondary to EHPVO.

PMID- 23132325
TI  - Application of Suzuki arylation, Sonogashira ethynylation and Rosenmund-von Braun
      cyanation in the exploration of substitution effects on the anticancer activity
      of 2-aroylquinolines.
AB  - A variety of functionalities were introduced at 2-aroylquinoline's C5 position,
      which is considered equivalent to C-3' of the B-ring of CA4, via Suzuki
      arylation, Sonogashira ethynylation, and Rosenmund-von Braun cyanation. These
      substitutions are rarely utilized in the modification of 3'-OH of CA4. The
      resulting products 6 and 7 having cyano and ethynyl groups exhibited comparable
      antiproliferative and tubulin inhibitory activities to colchicine.

PMID- 23132326
TI  - Detection of Leishmania infantum in animals and their ectoparasites by
      conventional PCR and real time PCR.
AB  - Visceral leishmaniosis (VL) is a parasitic disease caused by Leishmania infantum,
      which is primarily transmitted by phlebotomine sandflies. However, there has been
      much speculation on the role of other arthropods in the transmission of VL. Thus,
      the aim of this study was to assess the presence of L. infantum in cats, dogs and
      their ectoparasites in a VL-endemic area in northeastern Brazil. DNA was
      extracted from blood samples and ectoparasites, tested by conventional PCR (cPCR)
      and quantitative real time PCR (qPCR) targeting the L. infantum kinetoplast DNA.
      A total of 280 blood samples (from five cats and 275 dogs) and 117 ectoparasites
      from dogs were collected. Animals were apparently healthy and not previously
      tested by serological or molecular diagnostic methods. Overall, 213 (76.1 %)
      animals and 51 (43.6 %) ectoparasites were positive to L. infantum, with mean
      parasite loads of 795.2, 31.9 and 9.1 fg in dogs, cats and ectoparasites,
      respectively. Concerning the positivity between dogs and their ectoparasites, 32
      (15.3 %) positive dogs were parasitized by positive ectoparasites. The overall
      concordance between the PCR protocols used was 59.2 %, with qPCR being more
      efficient than cPCR; 34.1 % of all positive samples were exclusively positive by
      qPCR. The high number of positive animals and ectoparasites also indicates that
      they could serve as sentinels or indicators of the circulation of L. infantum in
      risk areas.

PMID- 23132329
TI  - Excited-state intramolecular proton transfer and charge transfer in 2-(2'
      hydroxyphenyl)benzimidazole crystals studied by polymorphs-selected electronic
      spectroscopy.
AB  - Crystal structures of polymorphs of 2-(2'-hydroxyphenyl)benzimidazole (HPBI),
      Forms alpha and beta, are analyzed by X-ray crystallography. The fluorescence
      excitation (FE) and fluorescence spectra of the polymorphs are separately
      observed at temperatures 77-298 K. It has been found that the electronic spectra
      of the two crystal forms are significantly different from each other. Photo
      excitation of the enol forms in Forms alpha and beta induces the excited-state
      intramolecular proton transfer (ESIPT) to produce the S(1) state of the keto
      forms. In the FE spectra of Forms alpha and beta, the S(1) <- S(0) (pipi*)
      transition of the keto form is observed in the 360-420 nm region in addition to
      that of the enol form in the 250-420 nm region. In the FE spectrum of Form beta a
      new band peaking at 305 nm is observed, which is assigned to the S(1) <- S(0)
      transition of a non-planar enol form based on the observation of dual
      fluorescence in the UV and visible regions and quantum chemical calculation on
      the transition energy against the twisted angle between the benzimidazole and
      hydroxyphenyl rings. The fluorescence quantum yield (phi(T)) for the keto form is
      remarkably dependent on polymorphs at room temperature; phi(T) = 0.53 for Form
      alpha is much larger than phi(T) <= 0.23 for Form beta. At 77 K the phi(T) values
      for Forms alpha and beta increase to 0.67 and <=0.57, respectively. The changes
      in the phi(T) values are associated with the intramolecular charge transfer (ICT)
      state. The potential barrier height between the S(1)-keto and S(1)-ICT states is
      significantly lower for Form beta than for Form alpha. At 77 K the S(1)-keto ->
      S(1)-ICT process followed by S(1)-ICT -> S(0)-keto internal conversion is
      significantly suppressed in Form beta. We compare difference in the dynamics
      between Forms alpha and beta in the electronic ground and excited states.

PMID- 23132328
TI  - Scriptaid, a novel histone deacetylase inhibitor, protects against traumatic
      brain injury via modulation of PTEN and AKT pathway : scriptaid protects against
      TBI via AKT.
AB  - Traumatic brain injury (TBI) is a leading cause of motor and cognitive deficits
      in young adults for which there is no effective therapy. The present study
      characterizes the protective effect of a new histone deacetylase inhibitor,
      Scriptaid (Sigma-Aldrich Corporation, St. Louis, MO), against injury from
      controlled cortical impact (CCI). Scriptaid elicited a dose-dependent decrease in
      lesion size at 1.5 to 5.5 mg/kg and a concomitant attenuation in motor and
      cognitive deficits when delivered 30 minutes postinjury in a model of moderate
      TBI. Comparable protection was achieved even when treatment was delayed to 12 h
      postinjury. Furthermore, the protection of motor and cognitive functions was long
      lasting, as similar improvements were detected 35 days postinjury. The efficacy
      of Scriptaid (Sigma-Aldrich Corporation) was manifested as an increase in
      surviving neurons, as well as the number/length of their processes within the CA3
      region of the hippocampus and the pericontusional cortex. Consistent with other
      histone deacetylase inhibitors, Scriptaid treatment prevented the decrease in
      phospho-AKT (p-AKT) and phosphorylated phosphatase and tensin homolog deleted on
      chromosome 10 (p-PTEN) induced by TBI in cortical and CA3 hippocampal neurons.
      Notably, the p-AKT inhibitor LY294002 attenuated the impact of Scriptaid,
      providing mechanistic evidence that Scriptaid functions partly by modulating the
      prosurvival AKT signaling pathway. As Scriptaid offers long-lasting neuronal and
      behavioral protection, even when delivered 12 h after controlled cortical impact,
      it is an excellent new candidate for the effective clinical treatment of TBI.

PMID- 23132327
TI  - Neuroinflammatory imaging biomarkers: relevance to multiple sclerosis and its
      therapy.
AB  - Magnetic resonance imaging is an established tool in the management of multiple
      sclerosis (MS). Loss of blood brain barrier integrity assessed by gadolinium (Gd)
      enhancement is the current standard marker of MS activity. To explore the complex
      cascade of the inflammatory events, other magnetic resonance imaging, but also
      positron emission tomographic markers reviewed in this article are being
      developed to address active neuroinflammation with increased sensitivity and
      specificity. Alternative magnetic resonance contrast agents, positron emission
      tomographic tracers and imaging techniques could be more sensitive than Gd to
      early blood brain barrier alteration, and they could assess the inflammatory cell
      recruitment and/or the associated edema accumulation. These markers of active
      neuroinflammation, although some of them are limited to experimental studies,
      could find great relevance to complete Gd information and thereby increase our
      understanding of acute lesion pathophysiology and its noninvasive follow-up,
      especially to monitor treatment efficacy. Furthermore, such accurate markers of
      inflammation combined with those of neurodegeneration hold promise to provide a
      more complete picture of MS, which will be of great benefit for future
      therapeutic strategies.

PMID- 23132330
TI  - Diabetes mellitus and trends in hospital survival after myocardial infarction,
      1994 to 2006: data from the national registry of myocardial infarction.
AB  - BACKGROUND: Patients with diabetes mellitus (DM) are at high risk for mortality
      after myocardial infarction (MI). Despite an overall trend of reduced mortality
      after MI, the mortality gap between MI patients with and without DM did not
      decrease over time in previous analyses. We assessed recent trends in hospital
      mortality for patients with MI according to DM status. METHODS AND RESULTS: We
      analyzed data from the National Registry of Myocardial Infarction, a contemporary
      registry of MI patients treated in 1964 hospitals, representing approximately one
      fourth of all US acute care hospitals. The study comprised 1734431 MI patients
      enrolled from 1994 to 2006, including 502315 (29%) with DM. Crude hospital
      mortality decreased in all patients between 1994 and 2006 but remained higher in
      patients with DM compared with those without DM throughout the study. The
      absolute difference in mortality between patients with and without DM
      significantly narrowed over time, from 15.6% versus 11.5% in 1994 to 8.0% versus
      6.8% in 2006 (P<0.001 for DM * time interaction). The adjusted odds ratio for
      mortality associated with DM declined from 1.24 (95% confidence interval, 1.16
      1.32) in 1994 to 1.08 (95% confidence interval, 0.99-1.19) in 2006 (P<0.001 for
      trend). The largest improvement in hospital mortality was observed in diabetic
      women (17.9% in 1994 versus 8.4% in 2006; P<0.001). CONCLUSIONS: The hospital
      mortality gap between MI patients with and without DM narrowed significantly from
      1994 to 2006, with the greatest improvement observed in women with DM.

PMID- 23132331
TI  - How small is too small? A systematic review of center volume and outcome after
      cardiac transplantation.
AB  - BACKGROUND: The aim of this study was to assess the relationship between the
      volume of cardiac transplantation procedures performed in a center and the
      outcome after cardiac transplantation. METHODS AND RESULTS: PubMed, Embase, and
      the Cochrane library were searched for articles on the volume-outcome
      relationship in cardiac transplantation. Ten studies were identified, and all
      adopted a different approach to data analysis and varied in adjustment for
      baseline characteristics. The number of patients in each study ranged from 798 to
      14401, and observed 1-year mortality ranged from 12.6% to 34%. There was no
      association between the continuous variables of center volume and observed
      mortality. There was a weak association between the continuous variables of
      center volume and adjusted mortality up to 1 year and a stronger association at 5
      years. When centers were grouped in volume categories, low-volume centers had the
      highest adjusted mortality, intermediate-volume centers had lower adjusted
      mortality, and high-volume centers had the lowest adjusted mortality but were not
      significantly better than intermediate-volume centers. Category limits were
      arbitrary and varied between studies. CONCLUSIONS: There is a relationship
      between center volume and mortality in heart transplantation. The existence of a
      minimum acceptable center volume or threshold is unproven. However, a level of 10
      to 12 heart transplants per year corresponds to the upper limit of low-volume
      categories that may have relatively higher mortality. It is not known whether
      outcomes for patients treated in low-volume transplant centers would be improved
      by reorganizing centers to ensure volumes in excess of 10 to 12 heart transplants
      per year.

PMID- 23132334
TI  - In vitro investigations into the roles of drug transporters and metabolizing
      enzymes in the disposition and drug interactions of dolutegravir, a HIV integrase
      inhibitor.
AB  - Dolutegravir (DTG; S/GSK1349572) is a potent HIV-1 integrase inhibitor with a
      distinct resistance profile and a once-daily dose regimen that does not require
      pharmacokinetic boosting. This work investigated the in vitro drug transport and
      metabolism of DTG and assessed the potential for clinical drug-drug interactions.
      DTG is a substrate for the efflux transporters P-glycoprotein (Pgp) and human
      breast cancer resistance protein (BCRP). Its high intrinsic membrane permeability
      limits the impact these transporters have on DTG's intestinal absorption. UDP
      glucuronosyltransferase (UGT) 1A1 is the main enzyme responsible for the
      metabolism of DTG in vivo, with cytochrome P450 (P450) 3A4 being a notable
      pathway and UGT1A3 and UGT1A9 being only minor pathways. DTG demonstrated little
      or no inhibition (IC(50) values > 30 MUM) in vitro of the transporters Pgp, BCRP,
      multidrug resistance protein 2, organic anion transporting polypeptide 1B1/3,
      organic cation transporter (OCT) 1, or the drug metabolizing enzymes CYP1A2, 2A6,
      2B6, 2C8, 2C9, 2C19, 2D6, 3A4, UGT1A1, or 2B7. Further, DTG did not induce
      CYP1A2, 2B6, or 3A4 mRNA in vitro using human hepatocytes. DTG does inhibit the
      renal OCT2 (IC(50) = 1.9 MUM) transporter, which provides a mechanistic basis for
      the mild increases in serum creatinine observed in clinical studies. These in
      vitro studies demonstrate a low propensity for DTG to be a perpetrator of
      clinical drug interactions and provide a basis for predicting when other drugs
      could result in a drug interaction with DTG.

PMID- 23132335
TI  - Phase 2 trial of concurrent bevacizumab and transhepatic arterial
      chemoembolization in patients with unresectable hepatocellular carcinoma.
AB  - BACKGROUND: Vascular endothelial growth factor is up-regulated in hepatocellular
      carcinoma (HCC) and is further up-regulated after transhepatic arterial
      chemoembolization. The authors of this report conducted a phase 2 trial to
      evaluate the safety and efficacy of bevacizumab combined with chemoembolization
      in patients with unresectable HCC. METHODS: Patients who had an Eastern
      Cooperative Oncology Group performance of status 0 to 2, a Child-Pugh score of A
      or B, and Barcelona Clinic Liver Cancer stage B or C HCC were eligible. Treatment
      consisted of bevacizumab every 2 weeks and chemoembolization during the third
      week of a 6-week cycle for up to 3 cycles over 6 months. The primary endpoints
      were safety and efficacy. RESULTS: Twenty-five patients received
      chemoembolization and bevacizumab. The most common grade 3 and 4 events after the
      first treatment cycle were leukocytopenia (12%), fatigue (12%), and hyponatremia
      (12%). Serious toxicities that had a known association with bevacizumab were
      observed in 4 patients. Thirty-day mortality was 0%. The median time to tumor
      progression for the targeted lesions was not reached, and overall survival was
      10.8 months. The objective response rate was 60% using enhancement response
      evaluation criteria, and the disease control rate was 100%. CONCLUSIONS:
      Concurrent treatment with bevacizumab and chemoembolization was safe in carefully
      selected patients and demonstrated antitumor activity in patients with
      unresectable HCC. These results support the further development of bevacizumab
      combined with chemoembolization as a treatment for unresectable HCC.

PMID- 23132336
TI  - 32-channel phased-array receive with asymmetric birdcage transmit coil for
      hyperpolarized xenon-129 lung imaging.
AB  - Hyperpolarized xenon-129 has the potential to become a noninvasive contrast agent
      for lung MRI. In addition to its utility for imaging of ventilated airspaces, the
      property of xenon to dissolve in lung tissue and blood upon inhalation provides
      the opportunity to study gas exchange. Implementations of imaging protocols for
      obtaining regional parameters that exploit the dissolved phase are limited by the
      available signal-to-noise ratio, excitation homogeneity, and length of
      acquisition times. To address these challenges, a 32-channel receive-array coil
      complemented by an asymmetric birdcage transmit coil tuned to the hyperpolarized
      xenon-129 resonance at 3 T was developed. First results of spin-density imaging
      in healthy subjects and subjects with obstructive lung disease demonstrated the
      improvements in image quality by high-resolution ventilation images with high
      signal-to-noise ratio. Parallel imaging performance of the phased-array coil was
      demonstrated by acceleration factors up to three in 2D acquisitions and up to six
      in 3D acquisitions. Transmit-field maps showed a regional variation of only 8%
      across the whole lung. The newly developed phased-array receive coil with the
      birdcage transmit coil will lead to an improvement in existing imaging protocols,
      but moreover enable the development of new, functional lung imaging protocols
      based on the improvements in excitation homogeneity, signal-to-noise ratio, and
      acquisition speed.

PMID- 23132337
TI  - Regression of rubeosis in the fellow eye after intravitreal ranibizumab
      injection.

PMID- 23132338
TI  - Syntaxin-3 regulates newcomer insulin granule exocytosis and compound fusion in
      pancreatic beta cells.
AB  - AIMS/HYPOTHESIS: The molecular basis of the exocytosis of secretory insulin
      containing granules (SGs) during biphasic glucose-stimulated insulin secretion
      (GSIS) from pancreatic beta cells remains unclear. Syntaxin (SYN)-1A and SYN-4
      have been shown to mediate insulin exocytosis. The insulin-secretory function of
      SYN-3, which is particularly abundant in SGs, is unclear. METHODS: Mouse
      pancreatic islets and INS-1 cells were treated with adenovirus carrying Syn-3
      (also known as Stx3) or small interfering RNA targeting Syn-3 in order to examine
      insulin secretion by radioimmunoassay. The localisation and distribution of
      insulin granules were examined by confocal and electron microscopy. Dynamic
      single-granule fusion events were assessed using total internal reflection
      fluorescence microscopy (TIRFM). RESULTS: Depletion of endogenous SYN-3 inhibited
      insulin release. TIRFM showed no change in the number or fusion competence of
      previously docked SGs but, instead, a marked reduction in the recruitment of
      newcomer SGs and their subsequent exocytotic fusion during biphasic GSIS.
      Conversely, overexpression of Syn-3 enhanced both phases of GSIS, owing to the
      increase in newcomer SGs and, remarkably, to increased SG-SG fusion, which was
      confirmed by electron microscopy. CONCLUSIONS/INTERPRETATION: In insulin
      secretion, SYN-3 plays a role in the mediation of newcomer SG exocytosis and SG
      SG fusion that contributes to biphasic GSIS.

PMID- 23132339
TI  - Signalling danger: endoplasmic reticulum stress and the unfolded protein response
      in pancreatic islet inflammation.
AB  - Protein synthesis is increased by several-fold in stimulated pancreatic beta
      cells. Synthesis and folding of (pro)insulin takes place in the endoplasmic
      reticulum (ER), and beta cells trigger the unfolded protein response (UPR) to
      upgrade the functional capacity of the ER. Prolonged or excessive UPR activation
      contributes to beta cell dysfunction and death in type 2 diabetes, but there is
      another side of the UPR that may be of particular relevance for autoimmune type 1
      diabetes, namely, the cross-talk between the UPR and innate
      immunity/inflammation. Recent evidence, discussed in this review, indicates that
      both saturated fats and inflammatory mediators such as cytokines trigger the UPR
      in pancreatic beta cells. The UPR potentiates activation of nuclear factor
      kappaB, a key regulator of inflammation. Two branches of the UPR, namely
      IRE1/XBP1s and PERK/ATF4/CHOP, mediate the UPR-induced sensitisation of
      pancreatic beta cells to the proinflammatory effects of cytokines. This can
      contribute to the upregulation of local inflammatory mechanisms and the
      aggravation of insulitis. The dialogue between the UPR and inflammation may
      provide an explanation for the parallel increase in the prevalence of childhood
      obesity and type 1 diabetes.

PMID- 23132341
TI  - Viable quantitative PCR for assessing the response of Candida albicans to
      antifungal treatment.
AB  - Propidium monoazide (PMA) or ethidium bromide monoazide (EMA) treatment has been
      used before nucleic acid detection methods, such as PCR, to distinguish between
      live and dead cells using membrane integrity as viability criterion. The
      performance of these DNA intercalating dyes was compared in many studies
      utilizing different microorganisms. These studies demonstrated that EMA and PMA
      differ in their abilities to identify nonviable cells from mixed cell
      populations, depending on the microorganism and the nature of the sample. Due to
      this heterogeneity, both dyes were used in the present study to specifically
      distinguish dead from live Candida albicans cells using viable quantitative PCR
      (qPCR). The viable qPCR was optimized, and the best results were obtained when
      pre-treating the cells for 10 min in the dark with 25 MUM EMA followed by
      continuous photoactivation for 15 min. The suitability of this technique to
      distinguish clotrimazole- and fluconazole-treated C. albicans cells from
      untreated cells was then assessed. Furthermore, the antifungal properties of two
      commercial essential oils (Thymus vulgaris and Matricaria chamomilla) were
      evaluated. The viable qPCR method was determined to be a feasible technique for
      assessing the viability of C. albicans after drug treatment and may help to
      provide a rapid diagnostic and susceptibility testing method for fungal
      infections, especially for patients treated with antifungal therapies.

PMID- 23132340
TI  - Oestrogens improve human pancreatic islet transplantation in a mouse model of
      insulin deficient diabetes.
AB  - AIMS/HYPOTHESIS: Pancreatic islet transplantation (PIT) offers a physiological
      treatment for type 1 diabetes, but the failure of islet engraftment hinders its
      application. The female hormone 17beta-oestradiol (E2) favours islet survival and
      stimulates angiogenesis, raising the possibility that E2 may enhance islet
      engraftment following PIT. METHODS: To explore this hypothesis, we used an
      insulin-deficient model with xenotransplantation of a marginal dose of human
      islets in nude mice rendered diabetic with streptozotocin. This was followed by 4
      weeks of treatment with vehicle, E2, the non-feminising oestrogen 17alpha
      oestradiol (17alpha-E2), the oestrogen receptor (ER) alpha agonist propyl
      pyrazole-triol (PPT), the ERbeta agonist diarylpropionitrile (DPN) or the G
      protein-coupled oestrogen receptor (GPER) agonist G1. RESULTS: Treatment with E2,
      17alpha-E2, PPT, DPN or G1 acutely improved blood glucose and eventually promoted
      islet engraftment, thus reversing diabetes. The effects of E2 were retained in
      the presence of immunosuppression and persisted after discontinuation of E2
      treatment. E2 produced an acute decrease in graft hypoxic damage and suppressed
      beta cell apoptosis. E2 also acutely suppressed hyperglucagonaemia without
      altering insulin secretion, leading to normalisation of blood glucose.
      CONCLUSIONS/INTERPRETATION: During PIT, E2 synergistic actions contribute to
      enhancing human islet-graft survival, revascularisation and functional mass. This
      study identifies E2 as a short-term treatment to improve PIT.

PMID- 23132342
TI  - Ectoine-mediated protection of enzyme from the effect of pH and temperature
      stress: a study using Bacillus halodurans xylanase as a model.
AB  - Compatible solutes are small, soluble organic compounds that have the ability to
      stabilise proteins against various stress conditions. In this study, the
      protective effect of ectoines against pH stress is examined using a recombinant
      xylanase from Bacillus halodurans as a model. Ectoines improved the enzyme
      stability at low (4.5 and 5.0) and high pH (11 and 12); stabilisation effect of
      hydroxyectoine was superior to that of ectoine and trehalose. In the presence of
      hydroxyectoine, residual activity (after 10 h heating at 50  degrees C) increased
      from about 45 to 86 % at pH 5 and from 33 to 89 % at pH 12. When the xylanase was
      incubated at 65  degrees C for 5 h with 50 mM hydroxyectoine at pH 10, about 40 %
      of the original activity was retained while no residual activity was detected in
      the absence of additives or in the presence of ectoine or trehalose. The xylanase
      activity was slightly stimulated in the presence of 25 mM ectoines and then
      gradually decreased with increase in ectoines concentration. The thermal
      unfolding of the enzyme in the presence of the compatible solutes showed a modest
      increase in denaturation temperature but a larger increase in calorimetric
      enthalpy. 

PMID- 23132343
TI  - Pyrosequence analyses of bacterial communities during simulated in situ
      bioremediation of polycyclic aromatic hydrocarbon-contaminated soil.
AB  - Barcoded amplicon pyrosequencing was used to generate libraries of partial 16S
      rRNA genes from two columns designed to simulate in situ bioremediation of
      polycyclic aromatic hydrocarbons (PAHs) in weathered, contaminated soil. Both
      columns received a continuous flow of artificial groundwater but one of the
      columns additionally tested the impact of biostimulation with oxygen and
      inorganic nutrients on indigenous soil bacterial communities. The penetration of
      oxygen to previously anoxic regions of the columns resulted in the most
      significant community changes. PAH-degrading bacteria previously determined by
      stable-isotope probing (SIP) of the untreated soil generally responded negatively
      to the treatment conditions, with only members of the Acidovorax and a group of
      uncharacterized PAH-degrading Gammaproteobacteria maintaining a significant
      presence in the columns. Additional groups of sequences associated with the
      Betaproteobacterial family Rhodocyclaceae (including those associated with PAH
      degradation in other soils), and the Thiobacillus, Thermomonas, and
      Bradyrhizobium genera were also present in high abundance in the biostimulated
      column. Similar community responses were previously observed during biostimulated
      ex situ treatment of the same soil in aerobic, slurry-phase bioreactors. While
      the low relative abundance of many SIP-determined groups in the column libraries
      may be a reflection of the slow removal of PAHs in that system, the similar
      response of known PAH degraders in a higher-rate bioreactor system suggests that
      alternative PAH-degrading bacteria, unidentified by SIP of the untreated soil,
      may also be enriched in engineered systems. 

PMID- 23132345
TI  - Characterization of an ammonium transporter in the oleaginous alga Chlorella
      protothecoides.
AB  - A suppression subtractive hybridization cDNA library was used to screen the
      differently expressed (up-regulated) genes in the photosynthesis-fermentation
      approach (PFA) of Chlorella protothecoides cultivation. A total of 87 clones were
      obtained and sequenced, in which 78 clones were homologous to known genes in
      databases. Among them, the ammonium transporter gene (CpAMT1) was characterized
      in detail. Quantitative real-time PCR showed that the expression of CpAMT1 was
      significantly induced by PFA and correlated with lipid accumulation. The up
      regulation of CpAMT1 was suppressed by glutamine, while the lipid biosynthesis
      was also inhibited. Further analysis showed that the expression of CpAMT1 was
      correlated with glutamine synthetase activity, suggesting that CpAMT1, along with
      glutamine synthetase/glutamate synthase, may be responsible for nitrogen sensing
      in C. protothecoides. Together, these results imply that the ammonium transporter
      CpAMT1 could be the initial sensor of nitrogen deficiency and channels the carbon
      excess toward lipid biosynthesis.

PMID- 23132346
TI  - Nanobiotechnology as a novel paradigm for enzyme immobilisation and stabilisation
      with potential applications in biodiesel production.
AB  - Nanobiotechnology is emerging as a new frontier of biotechnology. The potential
      applications of nanobiotechnology in bioenergy and biosensors have encouraged
      researchers in recent years to investigate new novel nanoscaffolds to build
      robust nanobiocatalytic systems. Enzymes, mainly hydrolytic class of enzyme, have
      been extensively immobilised on nanoscaffold support for long-term stabilisation
      by enhancing thermal, operational and storage catalytic potential. In the present
      report, novel nanoscaffold variants employed in the recent past for enzyme
      immobilisation, namely nanoparticles, nanofibres, nanotubes, nanopores,
      nanosheets and nanocomposites, are discussed in the context of lipase-mediated
      nanobiocatalysis. These nanocarriers have an inherently large surface area that
      leads to high enzyme loading and consequently high volumetric enzyme activity.
      Due to their high tensile strengths, nanoscale materials are often robust and
      resistant to breakage through mechanical shear in the running reactor making them
      suitable for multiple reuses. The optimisation of various nanosupports process
      parameters, such as the enzyme type and selection of suitable immobilisation
      method may help lead to the development of an efficient enzyme reactor. This
      might in turn offer a potential platform for exploring other enzymes for the
      development of stable nanobiocatalytic systems, which could help to address
      global environmental issues by facilitating the production of green energy. The
      successful validation of the feasibility of nanobiocatalysis for biodiesel
      production represents the beginning of a new field of research. The economic
      hurdles inherent in viably scaling nanobiocatalysts from a lab-scale to
      industrial biodiesel production are also discussed.

PMID- 23132347
TI  - Characterization of recombinant amylopullulanase (gt-apu) and truncated
      amylopullulanase (gt-apuT) of the extreme thermophile Geobacillus thermoleovorans
      NP33 and their action in starch saccharification.
AB  - A gene encoding amylopullulanase (gt-apu) of the extremely thermophilic
      Geobacillus thermoleovorans NP33 was cloned and expressed in Escherichia coli.
      The gene has an open reading frame of 4,965 bp that encodes a protein of 1,655
      amino acids with molecular mass of 182 kDa. The six conserved regions,
      characteristic of GH13 family, have been detected in gt-apu. The recombinant
      enzyme has only one active site for alpha-amylase and pullulanase activities
      based on the enzyme kinetic analyses in a system that contains starch as well as
      pullulan as competing substrates and response to inhibitors. The end-product
      analysis confirmed that this is an endoacting enzyme. The specific enzyme
      activities for alpha-amylase and pullulanase of the truncated amylopullulanase
      (gt-apuT) are higher than gt-apu. Both enzymes exhibited similar temperature (60 
      degrees C) and pH (7.0) optima, although gt-apuT possessed a higher
      thermostability than gt-apu. The overall catalytic efficiency (K(cat)/K(m)) of gt
      apuT is greater than that of gt-apu, with almost similar substrate specificities.
      The C-terminal region of gt-apu appeared to be non-essential, and furthermore, it
      negatively affects the substrate binding and stability of the enzyme.

PMID- 23132348
TI  - Decolorization of azo dyes by Geobacter metallireducens.
AB  - Geobacter metallireducens was found to be capable of decolorizing several azo
      dyes with different structures to various extents. Pyruvate, ethanol, acetate,
      propionate, and benzoate could support 66.3 +/- 2.6-93.7 +/- 2.1 % decolorization
      of 0.1 mM acid red 27 (AR27) in 40 h. The dependence of the specific
      decolorization rate on AR27 concentration (25 to 800 MUM) followed Michaelis
      Menten kinetics (K m = 186.9 +/- 1.4 MUMU, V max = 0.65 +/- 0.02 MUmol mg
      protein(-1) h(-1)). Enhanced AR27 decolorization was observed with the increase
      of cell concentrations ranging from 7.5 to 45 mgL(-1). AR27 decolorization by G.
      metallireducens was retarded by the presence of goethite, which competed
      electrons with AR27 and was reduced to Fe(II). The addition of low concentrations
      of humic acid (1-100 mgL(-1)) or 2-hydroxy-1,4-naphthoquinone (0.5-50 MUM) could
      improve the decolorization performance of G. metallireducens. High-performance
      liquid chromatography analysis suggested reductive pathway to be responsible for
      decolorization. This was the first study on azo dye decolorization by Geobacter
      strain and might improve our understanding of natural attenuation and
      bioremediation of environments polluted by azo dyes. 

PMID- 23132344
TI  - Proliferation of diversified clostridial species during biological soil
      disinfestation incorporated with plant biomass under various conditions.
AB  - Biological soil disinfestation (BSD) involves the anaerobic decomposition of
      plant biomass by microbial communities leading to control of plant pathogens. We
      analyzed bacterial communities in soil of a model experiment of BSD, as affected
      by biomass incorporation under various conditions, to find out the major
      anaerobic bacterial groups which emerged after BSD treatments. The soil was
      treated with Brassica juncea plants, wheat bran, or Avena strigosa plants,
      irrigated at 20 or 30 % moisture content and incubated at 25-30  degrees C for 17
      days. The population of Fusarium oxysporum f. sp. spinaciae incorporated at the
      start of the experiment declined markedly for some BSD conditions and rather high
      concentrations of acetate and butyrate were detected from these BSD-treated
      soils. The polymerase chain reaction-denaturing gradient gel electrophoresis
      analysis based on the V3 region of 16S rRNA gene sequences from the soil DNA
      revealed that bacterial profiles greatly changed according to the treatment
      conditions. Based on the clone library analysis, phylogenetically diverse
      clostridial species appeared exceedingly dominant in the bacterial community of
      BSD soil incorporated with Brassica plants or wheat bran, in which the pathogen
      was suppressed completely. Species in the class Clostridia such as Clostridium
      saccharobutylicum, Clostridium acetobutylicum, Clostridium xylanovorans,
      Oxobacter pfennigii, Clostridium pasteurianum, Clostridium sufflavum, Clostridium
      cylindrosporum, etc. were commonly recognized as closely related species of the
      dominant clone groups from these soil samples. 

PMID- 23132349
TI  - Recurrence of paroxysmal atrial fibrillation after cryoisolation of the pulmonary
      veins. Is a "redo" procedure using the cryoballoon useful?
AB  - BACKGROUND: Pulmonary vein (PV) isolation with the cryoballoon technique is an
      effective and safe method to treat patients with paroxysmal atrial fibrillation
      (AF). However, the optimal treatment strategy for patients with recurrences after
      this ablation is unclear. AIMS: The aim of this single centre study was to
      evaluate the efficacy and safety of a "redo" procedure using the cryoballoon in
      this patient cohort. The secondary study objectives were to determine the rate of
      reconduction for individual PVs of the patients undergoing "redo" ablation and
      potential predictors of persistent PV isolation (PVI). METHODS: Between April
      2006 and September 2009, all patients with paroxysmal AF recurrences after
      cryoballoon ablation a "redo" ablation with the cryoballoon was offered. PV
      conduction was determined and cryoapplications were performed in all reconnected
      PVs. Every 3 months, 7-day Holter ECG, symptom-driven transtelephonic ECG
      recordings, and questionnaires were collected for 12 months. RESULTS: Forty-seven
      patients underwent "redo" cryoballoon ablation. In all these patients, at least
      one PV with reconduction was found. Recurrent conduction was documented in 63 %
      of the left superior PV, 56 % of the left inferior PV, 43 % of the right superior
      PV, and 56 % of the right inferior PV. In 28 of the 47 patients (60 %), no AF
      recurrence was detectable during the 12-month follow-up (after 3 months blanking
      period). Rate of severe complications was low and not significantly different
      from that of the initial ablations. CONCLUSION: "Redo" ablation using cryoballoon
      technology may be an effective and safe method to treat patients with recurrence
      of paroxysmal AF after cryoballoon PVI.

PMID- 23132350
TI  - Long non-coding RNAs function annotation: a global prediction method based on bi
      colored networks.
AB  - More and more evidences demonstrate that the long non-coding RNAs (lncRNAs) play
      many key roles in diverse biological processes. There is a critical need to
      annotate the functions of increasing available lncRNAs. In this article, we try
      to apply a global network-based strategy to tackle this issue for the first time.
      We develop a bi-colored network based global function predictor, long non-coding
      RNA global function predictor ('lnc-GFP'), to predict probable functions for
      lncRNAs at large scale by integrating gene expression data and protein
      interaction data. The performance of lnc-GFP is evaluated on protein-coding and
      lncRNA genes. Cross-validation tests on protein-coding genes with known function
      annotations indicate that our method can achieve a precision up to 95%, with a
      suitable parameter setting. Among the 1713 lncRNAs in the bi-colored network, the
      1625 (94.9%) lncRNAs in the maximum connected component are all functionally
      characterized. For the lncRNAs expressed in mouse embryo stem cells and neuronal
      cells, the inferred putative functions by our method highly match those in the
      known literature.

PMID- 23132351
TI  - Comparative effectiveness of chemotherapy in elderly patients with metastatic
      colorectal cancer.
AB  - PURPOSE: Treatment advances have improved outcomes in clinical trials of patients
      with metastatic colorectal cancer (mCRC). Less is known about these effects for
      patients in real-world settings. This study evaluated treatment patterns and
      survival in older, demographically diverse patients with mCRC. METHODS: A
      retrospective cohort analysis was performed for 4,250 patients from January 1,
      2000 to December 31, 2007 using linked Surveillance, Epidemiology, and End
      Results-Medicare database. Patients were >= 66 years, enrolled in Medicare parts
      A and B, and received first-line treatment with fluorouracil and leucovorin (5
      FU/LV), capecitabine (CAP), 5-FU/LV plus oxaliplatin (FOLFOX), or CAP and
      oxaliplatin (CAPOX). Cox regression with backward elimination and propensity
      score-weighted Cox regression estimated relative risk of death. Date of last
      follow-up was December 2009. Statistical comparisons were made between 5-FU/LV
      vs. CAP and FOLFOX vs. CAPOX. RESULTS: Compared to 5-FU/LV, patients treated with
      CAP were older (mean age 78 vs. 76; P<0.0001) and more likely female (61 vs. 54
      %; P=0.0017), while patients receiving CAPOX and FOLFOX were similar in age (mean
      age 74 vs. 73; P=0.0924). Complications requiring medical resource utilization
      following initiation of therapy were significantly higher among patients
      administered with 5-FU/LV (54 %) vs. CAP (17 %; P<0.0001) and FOLFOX (75 %) vs.
      CAPOX (57 %; P<0.0001). The multivariate analysis revealed no significant
      differences in survival between 5-FU/LV and CAP and between FOLFOX and CAPOX.
      CONCLUSIONS: Overall survival was comparable between CAP and 5-FU/LV and between
      CAPOX and FOLFOX with fewer complications requiring medical resource utilization
      associated with CAP and CAPOX, thus confirming clinical trial results.

PMID- 23132352
TI  - The prevalence and associated risk factors of sleep disorder-related symptoms in
      pregnant women in China.
AB  - PURPOSE: The sleep disorder in pregnant women remains unfamiliar to perinatal
      care providers, resulting in lack of appropriate care. This study was designed to
      investigate the prevalence of sleep disorder-related symptoms in pregnant women
      and to identify the associated risk factors. METHODS: Married pregnant women were
      enrolled from their first trimester and followed up until delivery. Nonpregnant
      married healthy women were selected as controls. A survey questionnaire was
      administered to each of them. RESULTS: We successfully performed a survey to
      1,993 pregnant women and 598 nonpregnant women. The overall prevalence of sleep
      disorder-related symptoms in pregnant women was significantly higher than the
      controls (56.1 vs. 29.9 %, P < 0.05). There was higher prevalence of snoring
      (30.2 %), observed sleep apnea (1.1 %), mouth breathing (23.7 %), nocturnal
      arousal (46.5 %), insomnia (35.1 %), and daytime sleepiness (52.6 %) in pregnant
      women. There were no significant differences of the prevalence of bruxism (7.0
      vs. 6.7 %), sleep talking (8.1 vs. 7.2 %), and sleep walking (0.4 vs. 0.2 %)
      between the two groups (P > 0.05). Nocturnal sleep time (8.0 +/- 1.3 h) was less
      in the third trimester compared with the nonpregnant women (8.2 +/- 1.1 h) (P <
      0.05). Smoking (OR = 3.39), drinking (OR = 2.40), allergic rhinitis/asthma (OR =
      1.71), an obvious difference in neck circumference (OR = 1.11), and waistline (OR
      = 1.07) changes between the first and third trimesters were the risk factors for
      sleep disorder-related problems. CONCLUSIONS: There is a high prevalence of sleep
      disorder-related symptoms in pregnant women. Our data may provide a baseline for
      prevention and treatment of sleep disturbances in pregnant women.

PMID- 23132354
TI  - Quantification and identification of genetically modified maize events in non
      identity preserved maize samples in 2009 using an individual kernel detection
      system.
AB  - We investigated the GM maize grain content of non-identity preserved (non-IP)
      maize samples produced in 2009 in the USA using our individual kernel detection
      system, involving two multiplex qualitative PCR methods coupled to microchip
      electrophoresis and partially real-time PCR array analysis, to clarify how many
      GM event maize grains were present in the samples and which GM events frequently
      appeared in 2009. The average percentage and standard deviation of GM maize
      grains on a kernel basis in five non-IP sample lots were 81.9%+/-2.8%, the
      average percentage of single GM event grains was 46.9%, and the average
      percentage of stacked GM event grains was 35.0%. MON88017 grains and NK603 grains
      were the most frequently observed as single GM event grains. The most frequent
      stacked GM event grains were MON88017*MON810 grains. This study shows that our
      method can provide information about GM maize events present in imported maize
      samples on a kernel basis.

PMID- 23132353
TI  - Hydrotropic polymeric mixed micelles based on functional hyperbranched
      polyglycerol copolymers as hepatoma-targeting drug delivery system.
AB  - Mixed copolymer nanoparticles (NPs) self-assembled from beta-cyclodextrin-grafted
      hyperbranched polyglycerol (HPG-g-CD) and lactobionic acid (LA)-grafted
      hyperbranched polyglycerol (HPG-g-LA) were applied as carriers for a hydrophobic
      antitumor drug, paclitaxel (PTX), achieving hepatocellular carcinoma-targeted
      delivery. The resulting NPs exhibited high drug loading capacity and substantial
      stability in aqueous solution. In vitro drug release studies demonstrated a
      controlled drug release profile with increased release at acidic pH. Remarkably,
      tumor proliferation assays showed that PTX-loaded mixed copolymer NPs inhibited
      asialoglycoprotein (ASGP) receptor positive HepG2 cell proliferation in a
      concentration-dependent manner in comparison with ASGP receptor negative BGC-823
      cells. Moreover, the competition assay demonstrated that the small molecular LA
      inhibited the cellular uptake of the PTX-loaded mixed copolymer NPs, indicating
      the ASGP receptor-mediated endocytosis in HepG2 cells. In addition, the
      intracellular uptake tests by confocal laser scanning microscopy showed that the
      mixed copolymer NPs were more efficiently taken up by HepG2 cells compared with
      HPG-g-CD NPs. These results suggest a feasible application of the mixed copolymer
      NPs as nanocarriers for hepatoma-targeted delivery of potent antitumor drugs.

PMID- 23132355
TI  - Development and validation of event-specific quantitative PCR method for
      genetically modified maize MIR604.
AB  - A GM maize event, MIR604, has been widely distributed and an analytical method to
      quantify its content is required to monitor the validity of food labeling. Here
      we report a novel real-time PCR-based quantitation method for MIR604 maize. We
      developed real-time PCR assays specific for MIR604 using event-specific primers
      designed by the trait developer, and for maize endogenous starch synthase IIb
      gene (SSIIb). Then, we determined the conversion factor, which is required to
      calculate the weight-based GM maize content from the copy number ratio of MIR604
      specific DNA to the endogenous reference DNA. Finally, to validate the developed
      method, an interlaboratory collaborative trial according to the internationally
      harmonized guidelines was performed with blind samples containing MIR604 at the
      mixing levels of 0, 0.5, 1.0, 5.0 and 10.0%. The reproducibility (RSDr) of the
      developed method was evaluated to be less than 25%. The limit of quantitation of
      the method was estimated to be 0.5% based on the ISO 24276 guideline. These
      results suggested that the developed method would be suitable for practical
      quantitative analyses of MIR604 maize.

PMID- 23132356
TI  - [Species identification of animal hair present as a contaminant in food by PCR
      APLP method].
AB  - A rapid, simple and inexpensive method was developed for identifying the species
      of animal hair present as a contaminant in food. A polymerase chain reaction
      amplified product length polymorphism (PCR-APLP) assay was applied to identify
      hair from human and others (cat, dog, rabbit, rat and mouse) or livestock (pig,
      cattle, horse, sheep, goat and chicken). The PCR primers were designed to amplify
      partial sequences from the 16S rRNA gene to the NADH dehydrogenase subunit 1
      (ND1) gene of mitochondrial DNA (mtDNA), which generate different length
      fragments for different animal species. The PCR-APLP assay utilized two PCR
      reaction tubes, each of which contained one universal forward primer and six
      species-specific reverse primers (human, etc. or livestock). Simultaneous
      identification was possible by agarose gel electrophoresis of PCR products. The
      developed method was applied to identify the source species of 52 animal hair
      samples. The expected amplified product length was obtained from all samples.

PMID- 23132357
TI  - [Radioactive cesium analysis in radiation-tainted beef by gamma-ray spectrometry
      with germanium semiconductor detector].
AB  - The detection limit and precision of radioactive cesium measurement in beef by
      gamma-ray spectrometry with a germanium semiconductor detector were evaluated.
      Measurement for 2,000 seconds using a U-8 container (100 mL) provided a detection
      limit of radioactive cesium (the sum of 134Cs and 137Cs) of around 20 Bq/kg. The
      99% confidence interval of the measurement of provisional maximum residue limit
      level (491 Bq/kg) samples ranged from 447 to 535 Bq/kg. Beef is heterogeneous,
      containing muscle and complex fat layers. Depending on the sampled parts, the
      measurement value is variable. It was found that radioactive cesium content of
      the muscle layer was clearly different from that of fat, and slight differences
      were observed among parts of the sample (SD=16.9 Bq/kg), even though the same
      region (neck block) of beef sample was analyzed.

PMID- 23132358
TI  - [Application of a rapid and simple multi-residue method for determination of
      pesticide residues in drinking water and beverages using liquid chromatography
      tandem mass spectrometry].
AB  - A rapid and simple multi-residue method for determination of pesticides has been
      applied to drinking water and beverages. To a disposable polypropylene tube
      containing 10.0 g sample, 20 mL acetonitrile was added and the mixture was shaken
      vigorously for 1 min to extract pesticides. Then, 1 g sodium chloride and 4 g
      magnesium sulfate anhydrous were added, followed by vigorous shaking for 1 min
      and centrifugation to obtain the organic phase. The organic phase was processed
      with a graphite carbon black/PSA solid phase column. After concentration and
      reconstitution with 25% methanol containing aqueous solution, the test solution
      was analyzed with LC-MS/MS. Recovery tests of 91 pesticides fortified (0.02
      MUg/g) in 35 kinds of drinking water and beverages were conducted. The decline of
      recoveries in alcoholic beverages is considered to be due to the increase of
      organic phase volume owing to ethanol included in the alcoholic beverages. A
      simulation study was carried out with simulated alcoholic beverages, which
      consisted of 50% grape juice, with various amounts of ethanol and water, to
      examine pesticides recoveries and volume of the organic phase. The results
      suggested this method would be applicable both to alcoholic beverages containing
      less than 10% ethanol and to alcoholic beverages containing over 10% ethanol
      after dilution with water to below 10% ethanol prior to the addition of
      acetonitrile. A sample could be processed and analyzed by LC-MS/MS within 2 h.
      Thus, this method should be useful for monitoring and screening pesticide
      residues in drinking water and various beverages.

PMID- 23132359
TI  - Pain after median sternotomy: collateral damage or mitigatable byproduct?
AB  - BACKGROUND: Postoperative acute pain can cause anxiety and decrease the quality
      of life in patients. Acute sternal bone pain after cardiac surgery can persist
      for long time. OBJECTIVE: The aim of this study is to explore the relationships
      between the degree of sternal misalignment and the degree of acute sternal pain
      after coronary artery bypass grafting surgery (CABG). METHODS: We retrospectively
      reviewed postoperative coronary computed tomographic (CT) angiography and medical
      records in 104 patients who received CABG between May 1, 2009 and January 31,
      2011. CT scan was classified into five categories, and we compared the degree of
      misalignment and subjective pain via numerical rating scale (NRS) system.
      RESULTS: Positive correlation was noted between NRS and the degree of sternal
      misalignment (Pearson correlation coefficient 0.660, p = 0.000). CONCLUSION:
      Postoperative sternal pain is related to the degree of misalignment of the
      sternal halves. It would be appropriate for surgeons to approximate the sternal
      halves accurately to decrease the postoperative sternal wound pain in the first
      place.

PMID- 23132360
TI  - Gender-dependent differences in patients undergoing tricuspid valve surgery.
AB  - OBJECTIVES: The proportion of women in tricuspid valve (TV) surgery is almost 60%
      and above, especially in redo surgery. Is there a different epidemiology for male
      or female patients regarding the incidence of TV regurgitation? Are there
      differences in the peri- and postoperative outcome in male and female patients?
      In these questions, we were interested in and investigated our database of
      patients with isolated TV surgery. METHODS: We present a retrospective analysis
      of 92 patients (37 men and 55 women) undergoing isolated TV surgery due to
      symptomatic severe tricuspid regurgitation and/or due to active endocarditis
      between May 1997 and August 2010. Mean age was 60.5 +/- 15.8 years, mean log
      European System for Cardiac Operative Risk Evaluation (EuroSCORE) was 12.1 +/-
      11.3%, 51.4% of the operations were redos (men: 27%, women: 65%, p < 0.001), 36%
      due to active endocarditis (men: 62%, women: 18%, p < 0.001). Follow-up was 95%
      complete with a mean duration of 34.2 +/- 33.0 months. RESULTS: Overall 30-day
      mortality was 5.4% (men: 5.4% and women: 5.5%). Five-year survival was 70.2 +/-
      11.4 versus 76.3 +/- 6.8% (p = 0.3); 5-year freedom from TV-related reoperation
      was 95.8 +/- 4.1 versus 84.6 +/- 8.5% for men and women (p = 0.4). There was no
      significant gender-dependent difference regarding the global postoperative
      outcome. In a binary logistic regression analysis with the dependent variable
      gender, the categories age, log EuroSCORE, endocarditis, previous cardiac
      surgery, and preoperative cardiac rhythm, an odds ratio of 0.17 for men regarding
      the factor endocarditis (95% confidence interval [CI]: 0.05 to 0.57; p = 0.004)
      was shown, as well as an odds ratio of 3.2 for women regarding the factor
      previous cardiac surgery (95% CI: 1.0 to 10.1; p = 0.04) and an odds ratio of 5.9
      regarding the factor presence of a permanent pacemaker (95% CI: 1.4 to 24.7; p =
      0.02). CONCLUSIONS: We were not able to find significant gender-dependent
      differences in the postoperative outcome after isolated TV surgery, but there
      seem to be demographic gender-dependent differences regarding the reasons for TV
      surgery, which could influence the treatment of patients.

PMID- 23132361
TI  - ABVD alone and a PET scan complete remission negates the need for radiologic
      surveillance in early-stage, nonbulky Hodgkin lymphoma.
AB  - BACKGROUND: Patients with early-stage, nonbulky classic Hodgkin lymphoma (cHL)
      undergo intensive posttreatment radiologic surveillance despite having a low risk
      of disease recurrence. The current study attempted to evaluate the risk of
      disease recurrence and the value of radiologic surveillance in patients treated
      with the combination of doxorubicin, bleomycin, vinblastine, and dacarbazine
      (ABVD) alone who achieved a complete remission (CR) as noted on posttreatment
      positron emission tomography (PET). METHODS: Forty-seven patients who underwent
      therapy with interim and/or posttreatment PET scans were evaluated for disease
      recurrence during >= 24 months of follow-up. Their presenting characteristics and
      imaging results were assessed and interpreted in relation to clinical outcome.
      RESULTS: All 47 patients were eligible for analysis. The majority of patients
      were female (35 patients) with a median age of 28 years (range, 17 years-65
      years.). The nodular sclerosing subtype was the predominant histology (41
      patients). A total of 34 patients were staged with IIA disease, 6 with IA
      disease, 6 with IIB disease, and 1 with IIEA disease (lung) (according to
      Cotswolds modification of the Ann Arbor staging system). All patients completed 6
      cycles of planned ABVD therapy and achieved a CR. Two had a positive PET scan (1
      interim scan and 1 posttreatment scan); both were biopsy-proven sarcoidosis. Two
      patients developed disease recurrence at 7 months and 24 months, respectively,
      after negative interim and posttreatment imaging. One case of recurrence was
      identified through surveillance imaging and the other was identified
      simultaneously by the patient and surveillance scan. A total of 45 patients
      experienced a durable CR; 21 had additional unscheduled imaging/workup during
      surveillance to investigate symptoms or imaging signs of concern. CONCLUSIONS:
      Because of a low risk of disease recurrence, posttreatment radiologic
      surveillance appears to be unnecessary in patients with early-stage, nonbulky
      (CD20 negative) cHL who achieve a PET-detected CR with the ABVD combination
      alone. This will reduce cumulative radiation exposure and health care costs in a
      predominantly young patient population.

PMID- 23132362
TI  - Genotoxicity assessment of amaranth and allura red using Saccharomyces
      cerevisiae.
AB  - Amaranth (E123) and Allura red (E129), very important food azo dyes used in food,
      drug, paper, cosmetic and textile industries, were assessed for their genotoxic
      potential through comet assay in yeast cells. Comet assay was standardized by
      with different concentration of H(2)O(2). Concentrations of Amaranth and Allura
      red were maintained in sorbitol buffer starting from 9.76 to 5,000 MUg/mL and 1 *
      10(4) cells were incubated at two different incubation temperatures 28 and 37
      degrees C. Amaranth (E123) and Allura red (E129) were found to exhibit their
      genotoxic effect directly in Saccharomyces cerevisiae. No significant genotoxic
      activity was observed for Amaranth and Allura red at 28 degrees C but at 37
      degrees C direct relation of Amaranth concentration with comet tail was
      significant and no positive relation was seen with time exposure factor. At 37
      degrees C the minimum concentration of Amaranth and Allura red at which
      significant DNA damage observed through comet assay was 1,250 MUg/mL in 2nd h
      post exposure time. The results indicated that food colors should be carefully
      used in baking products as heavy concentration of food colors could affect the
      fermentation process of baking.

PMID- 23132363
TI  - Levels of organochlorine pesticide residues in butter samples collected from the
      Black Sea Region of Turkey.
AB  - The aim of the present study was to evaluate the levels of 9 organochlorine
      compounds (aldrin, hexachlorobenzene, 2,4-DDE, 4,4-DDE, 2,4-DDT, 4,4-DDT, and
      alpha-, beta-, and gamma-HCH) in butter samples collected in the Eastern, Middle
      and Western Black Sea Regions of Turkey between October 2009 and June 2010. The
      liquid-liquid extraction method was used to extract the organochlorine compounds
      from the samples and the measurements were performed by using a gas chromatograph
      electron capture detector system. DDT metabolites, aldrin, hexachlorobenzene
      (HCB), and alpha-, and gamma-HCH were not detected in the samples but beta-HCH
      was detected in 3 of a total of 88 samples. In the first period, only one sample
      from the West Black Sea Region was beta-HCH positive (0.014 mg kg(-1)). The other
      beta-HCH positive samples collected in Middle and West Black Sea Regions in the
      second period had a concentration of 0.066 and 0.019 mg kg(-1), respectively. All
      concentrations of the detected compounds exceeded the legal limits of 0.003 mg
      kg(-1) for beta-HCH, as prescribed by the Turkish Food Codex, and therefore pose
      a potential health risk for consumers. The contamination detected is most likely
      due to the past usage of beta-HCH in agriculture and its long term persistence in
      the environment. These results strongly suggest that further research should be
      focused on the detection of pesticide residues in agricultural areas across the
      nation.

PMID- 23132364
TI  - Bioconcentration and arsenic speciation analysis in ragworm, Hediste diversicolor
      (Muller 1776).
AB  - This study focused on bioconcentrations of arsenic in Hediste diversicolor
      (Muller 1776) after exposure to three different molecule solutions: arsenate,
      dimethyl-arsinate and arsenobetaine. Speciation analysis was carried out after
      exposing the organisms to these solutions in order to investigate their arsenic
      biotransformation capacity. Arsenic reached to the maximum level in these tissues
      after 15 days' exposure to a solution of 100 MUg L(-1) of arsenobetaine, although
      a significant increase was obtained in worms exposed to arsenate. Speciation
      analysis shows that trimethyl-arsine oxide is the slowest detoxification phase
      recorded in experiment.

PMID- 23132365
TI  - Contamination of selected organochlorine pesticides (OCPs) in sediment from
      CauBay River, Hanoi.
AB  - This work investigated the contamination status of selected organochlorine
      pesticides (OCPs: p,p'-DDT, p,p'-DDE, p,p'-DDD, alpha, beta, gamma, delta-HCH) in
      sediment of the CauBay river. Wide occurrence and remarkable residue levels of
      these two OCPs have been found in the study areas. SigmaDDT concentrations ranged
      from 51.84 to 92.76 ng.g(-1) dry weight, whereas SigmaHCH concentrations ranged
      from 4.56 to 11.39 ng g(-1) dry weight. All of the sampling sites exceeded the
      effects range median levels for DDT (>46.1 ng g(-1)). The analyzed results show
      that SigmaDDT and SigmaHCH displayed uniform high and low distribution,
      respectively. There is no recent input of DDT and HCH in the study area.

PMID- 23132366
TI  - Determination of water sources contamination to diazinon and malathion and
      spatial pollution patterns in Qazvin, Iran.
AB  - A questionnaire study and field visit showed that diazinon and malathion were the
      most commonly used pesticides in Qazvin province, Iran. Concentrations of these
      pesticides were determined in water sources; include springs, wells and Shahrood
      River. Springs water samples had the best water quality; but deep wells were the
      most polluted water samples. Diazinon was detected in 46.6 % of the samples,
      while malathion occurrences frequency was in 13.3 % of the samples. Diazinon and
      malathion were detected in maximum concentration of 19.44 and 18.12 MUg L(-1),
      respectively. The obtained results showed that diazinon was detected in higher
      than life-time health advisories in wells and in Shahrood River samples; so, it
      can bring up threats to human health. Interpolation of diazinon and malathion in
      water sources showed that diazinon had the most widely scattering condition in
      deep wells. Also, cross validation with the root mean square error (RMSE)
      indicated that the natural neighbor interpolation of malathion has the minimum
      RMSE.

PMID- 23132367
TI  - Fertility and life expectancy of a predatory stinkbug to sublethal doses of a
      pyrethroid.
AB  - Podisus distinctus (Heteroptera: Pentatomidae) is an important predator used in
      biological control of eucalypt defoliating caterpillars, exposed the
      insecticides. Lower doses of permethrin not affect the values of generation time
      (T), time necessary to double the population in number of individuals (DT) and
      intrinsic rate of population increase (r ( m )). Moreover, females of P.
      distinctus derived from nymphs treated with lower doses of permethrin were more
      fertile, triggering the effect hormetic in net reproductive rates (Ro). Results
      showed that low permethrin doses can be used alongside the predatory stinkbug in
      Integrated Pest Management programs.

PMID- 23132369
TI  - TGFbeta1-dependent podocyte dysfunction.
AB  - PURPOSE OF REVIEW: The glomerular filtration barrier is a unique structure
      characterized by a specialized framework of podocytes. Transforming growth factor
      beta1 (TGFbeta1) upregulation occurs in virtually all chronic kidney diseases and
      is associated with podocyte injury and proteinuria. This review is aimed at
      describing the latest advances made in the understanding of TGFbeta-induced
      podocyte injury. RECENT FINDINGS: During the past decade, progress has been made
      in understanding the biology and mechanisms of TGFbeta-induced podocyte injury.
      Most forms of glomerular diseases, including diabetic nephropathy, are associated
      with increased TGFbeta1 signaling and thus TGFbeta1 plays a central role in the
      pathogenesis of podocytopathy. The mechanism of podocyte injury is complex,
      involving a number of independent and overlapping cellular and molecular
      pathways. This review will examine these direct and indirect effects of TGFbeta1
      on podocyte dysregulation as reflected in their growth, differentiation, and
      motility. SUMMARY: These new developments in understanding the podocyte response
      to injury are critical for establishing better therapeutic interventions that
      target specific pathways, which otherwise could lead to irreversible injury.

PMID- 23132368
TI  - Renal microvascular dysfunction, hypertension and CKD progression.
AB  - PURPOSE OF REVIEW: Despite apparent blood pressure (BP) control and renin
      angiotensin system (RAS) blockade, the chronic kidney disease (CKD) outcomes have
      been suboptimal. Accordingly, this review is addressed to renal microvascular and
      autoregulatory impairments that underlie the enhanced dynamic glomerular BP
      transmission in CKD progression. RECENT FINDINGS: Clinical data suggest that
      failure to achieve adequate 24-h BP control is likely contributing to the
      suboptimal outcomes in CKD. Whereas evidence continues to accumulate regarding
      the importance of preglomerular autoregulatory impairment to the dynamic
      glomerular BP transmission, emerging data indicate that nitric oxide-mediated
      efferent vasodilation may play an important role in mitigating the consequences
      of glomerular hypertension. By contrast, the vasoconstrictor effects of
      angiotensin II are expected to potentially reduce glomerular barotrauma and
      possibly enhance ischemic injury. When adequate BP measurement methods are used,
      the evidence for BP-independent injury initiating mechanisms is considerably
      weaker and the renoprotection by RAS blockade largely parallels its
      antihypertensive effectiveness. SUMMARY: Adequate 24-h BP control presently
      offers the most feasible intervention for reducing glomerular BP transmission and
      improving suboptimal outcomes in CKD. Investigations addressed to improving
      myogenic autoregulation and/or enhancing nitric oxide-mediated efferent dilation
      in addition to the more downstream mediators may provide additional future
      therapeutic targets.

PMID- 23132370
TI  - Incomplete tumour control following DNA vaccination against rat gliomas
      expressing a model antigen.
AB  - BACKGROUND: Vaccination against tumour-associated antigens is one approach to
      elicit anti-tumour responses. We investigated the effect of polynucleotide (DNA)
      vaccination using a model antigen (E. coli lacZ) in a syngeneic gliosarcoma model
      (9L). METHODS: Fisher 344 rats were vaccinated thrice by intramuscular injection
      of a lacZ-encoding or a control plasmid in weekly intervals. One week after the
      last vaccination, lacZ-expressing 9L cells were implanted into the striatum.
      RESULTS: After 3 weeks, in lacZ-vaccinated animals the tumours were significantly
      smaller than in control-vaccinated animals. In cytotoxic T cell assays lysis
      rates of >50 % could only be observed in a few of the lacZ-vaccinated animals.
      This response was directed against lacZ-expressing and parental 9L cells but not
      against syngeneic MADB 106 adenocarcinoma cells. In Elispot assays interferon
      gamma production was observed upon stimulation with 9LlacZ and 9L wild-type but
      not MADB 106 cells. This response was higher for lacZ-immunized animals. All
      animals revealed dense infiltrates with CD8+ lymphocytes and, to a lesser extent,
      with NK cells. CD25-staining indicated cells possibly associated with the
      maintenance of peripheral tolerance to self-antigens. All tumours were densely
      infiltrated by microglia consisting mostly of ramified cells. Only focal
      accumulation of macrophage-like cells expressing ED1, a marker for phagocytic
      activity, was observed. CONCLUSION: Prophylactic DNA vaccination resulted in
      effective but incomplete suppression of brain tumour formation. Mechanisms other
      than cytotoxic T cell responses as measured in the generally used in vitro assays
      appear to play a role in tumour suppression.

PMID- 23132371
TI  - Targeted therapy with bevacizumab and erlotinib tailored to the molecular profile
      of patients with recurrent glioblastoma. Preliminary experience.
AB  - BACKGROUND: Advances in comprehension of molecular biology of glioblastoma (GBM)
      have led to the development of targeted therapies. The aim of the present study
      was to evaluate the efficacy and safety of a targeted therapeutic approach in
      which administration of bevacizumab and erlotinib was tailored on the molecular
      profile of recurrent GBM. METHODS: We prospectively enrolled ten adult patients
      suffering from recurrent GBM who had undergone surgical resection and standard
      chemo-radiotherapy. Tumor tissue was assessed for the expression of EGFRvIII and
      MGMT promoter methylation by RT-PCR, and for PTEN and VEGF expression by
      immunohistochemistry. Normal PTEN status was required for inclusion. Patients
      with VEGF overexpressing tumors (10/10) were treated with bevacizumab (10 mg/kg
      iv every 2 weeks in 6-week cycles); patients whose tumor expressed EGFRvIII
      (4/10) added erlotinib (150 mg/day orally; 300 mg/day if on enzyme-inducing
      antiepileptic drugs). Therapy was continued until disease progression or
      unacceptable toxicity. Primary endpoints of the study were response rate (RR), 6
      month progression-free survival (PFS-6), and safety profile. RESULTS: The RR and
      PFS-6 were 100 % (4/4) and 50 % (3/6) in patients treated with
      bevacizumab+erlotinib (n = 4) and bevacizumab (n = 6), respectively. In the whole
      cohort (n = 10), RR and PFS-6 were both 70 % (7/10); median PFS and overall
      survival (OS) were 8.0 (3.0-31.0) and 9.5 (5.0-31.0) months, respectively. No
      grade 3/4 adverse events were observed; three patients treated with
      bevacizumab+erlotinib displayed grade 1/2 rash not requiring dose reduction; one
      patient treated with bevacizumab developed intratumoral hemorrhage requiring
      treatment discontinuation. CONCLUSION: To our knowledge, this is the first study
      on recurrent GBM in which administration of bevacizumab and erlotinib was
      tailored on the molecular profile of the patient's tumor. Although we treated a
      limited number of patients, we obtained significantly higher RR and PFS-6 than
      those reported in a previous trial lacking molecular tumor analysis.

PMID- 23132372
TI  - Caught between a disc and a tumour: lumbar radiculopathy secondary to disc
      herniation and filum paraganglioma.

PMID- 23132373
TI  - Multiple reimplantation technique for treatment of complex giant aneurysms of the
      middle cerebral artery: technical note.
AB  - BACKGROUND: Giant middle cerebral artery (MCA) aneurysms are among the most
      challenging neurovascular lesions, especially when the M2 and M3 branches are
      incorporated into the aneurysm. Here we report on two cases with complex MCA
      aneurysms, in which double and triple arterial reimplantation of the efferent
      vessels into a saphenous vein graft (SVG) was applied to reconstruct the MCA
      tree, allowing final trapping of the aneurysm. METHODS: In the first case, a 41
      year-old woman presented with a partially thrombosed giant MCA aneurysm including
      three efferent branches. Two superior trunks were disconnected and reimplanted
      onto an SVG fed by the external carotid artery (ECA). Following anastomosis
      between the SVG and the inferior trunk, the aneurysm was trapped. The second case
      is a 67-year-old man with recurrent giant MCA aneurysm incorporating two efferent
      M2 branches. First, the superior trunk was reimplanted onto an SVG, then the SVG
      was anastomosed to the inferior trunk. Finally the afferent M1 was clipped.
      Intraoperative indocyanine green (ICG) videoangiography (FLOW 800) was used for
      studying bypass patency. RESULTS: In both cases, successful bypass patency was
      demonstrated by ICG videoangiography. Postoperative digital subtraction
      angiography (DSA) confirmed bypass patency. The first case was discharged without
      any neurological deficit. The second case suffered from bleeding due to refilling
      of the aneurysm via the inferior M2. An additional clip was placed on the
      inferior M2 in a second step. The patient was discharged with weakness of the
      left arm. CONCLUSION: Reconstructing an MCA bifurcation or trifurcation combining
      multiple arterial reimplantation is effective for treatment of selective cases of
      complex MCA aneurysms.

PMID- 23132374
TI  - Cost-utility of maximal safe resection of WHO grade II gliomas within eloquent
      areas.
AB  - BACKGROUND: Despite the growing use of intraoperative electrical stimulation
      (IES) mapping for resection of WHO grade II gliomas (GIIG) located within
      eloquent areas, some authors claim that this is a complex, time-consuming and
      expensive approach, and not well tolerated by patients, so they rely on other
      mapping techniques. Here we analyze the health related quality of life, direct
      and indirect costs of surgeries with and without intraoperative electrical
      stimulation (IES) mapping for resection of GIIG within eloquent areas. METHODS: A
      cohort of 11 subjects with GIIG within eloquent areas who had IES while awake
      (group A) was matched by tumor side and location to a cohort of 11 subjects who
      had general anesthesia without IES (group B). Direct and indirect costs (measured
      as loss of labor productivity) and utility (measured in quality adjusted life
      years, QALYs), were compared between groups. RESULTS: Total mean direct costs per
      patient were $38,662.70 (range $19,950.70 to $61,626.40) in group A, and
      $32,116.10 (range $22,764.50 to $46,222.50) in group B (p = 0.279). Total mean
      indirect costs per patient were $10,640.10 (range $3,010.10 to $86,940.70) in
      group A, and $48,804.70 (range $3,340.10 to $98,400.60) in group B (p = 0.035).
      Mean costs per QALY were $12,222.30 (range $3,801.10 to $47,422.90) in group A,
      and $31,927.10 (range $6,642.90 to $64,196.50) in group B (p = 0.023).
      CONCLUSIONS: Asleep-awake-asleep craniotomies with IES are associated with an
      increase in direct costs. However, these initial expenses are ultimately offset
      by medium and long-term costs averted from a decrease in morbidity and
      preservation of the patient's professional life. The present study emphasizes the
      importance to switch to an aggressive and safer surgical strategy in GIIG within
      eloquent areas.

PMID- 23132375
TI  - A rare vascular complication of transsphenoidal surgery.
AB  - We report a rare case of anterior cerebral artery (ACA) thrombosis following
      transsphenoidal surgery in a case of growth hormone secreting pituitary
      macroadenoma. During the surgery, there was arachnoid breach with cerebrospinal
      fluid (CSF) leak. Post operatively, she became blind in both eyes for which re
      exploration was done. A computed tomographic (CT) scan 16 hours after surgery
      showed a large tumor bed haematoma which was explored transcranially. During
      surgery, the right A1 was thrombosed while the ICA and middle cerebral artery
      (MCA) were patent as confirmed by post-operative magnetic resonance imaging
      (MRI). However, she died on the second post-operative day. ACA thrombosis
      following transsphenoidal surgery has not been reported before. A review of
      literature and possible mechanism of this complication has been discussed.

PMID- 23132376
TI  - Parametric proportional hazards model for mapping genomic imprinting of survival
      traits.
AB  - A number of imprinted genes have been observed in plants, animals and humans.
      They not only control growth and developmental traits, but may also be
      responsible for survival traits. Based on the Cox proportional hazards (PH)
      model, we constructed a general parametric model for dissecting genomic
      imprinting, in which a baseline hazard function is selectable for fitting the
      effects of imprinted quantitative trait loci (iQTL) genotypes on the survival
      curve. The expectation-maximisation (EM) algorithm is derived for solving the
      maximum likelihood estimates of iQTL parameters. The imprinting patterns of the
      detected iQTL are statistically tested under a series of null hypotheses. The
      Bayesian information criterion (BIC) model selection criterion is employed to
      choose an optimal baseline hazard function with maximum likelihood and
      parsimonious parameterisation. We applied the proposed approach to analyse the
      published data in an F(2) population of mice and concluded that, among five
      commonly used survival distributions, the log-logistic distribution is the
      optimal baseline hazard function for the survival time of hyperoxic acute lung
      injury (HALI). Under this optimal model, five QTL were detected, among which four
      are imprinted in different imprinting patterns.

PMID- 23132377
TI  - Theoretical studies on Grignard reagent formation: radical mechanism versus non
      radical mechanism.
AB  - Here we present a systematic theoretical investigation on the mechanisms of
      Grignard reagent formation (GRF) for CH(3)Cl reacting with Mg atom, Mg(2) and a
      series of Mg clusters (Mg(4)-Mg(20)). Our calculations reveal that the ground
      state Mg atom is inactive under matrix condition, whereas it is active under
      metal vapor synthesis (MVS) conditions. On the other hand, the excited state Mg
      ((3)P) atom, as produced by laser-ablation, can react with CH(3)Cl barrierlessly,
      and hence is active under matrix condition. We predict that the bimagnesium
      Grignard reagent, though often proposed, can barely be observed experimentally,
      due to its high reactivity towards additional CH(3)Cl to produce more stable
      Grignard reagent dimer, and that the cluster Grignard reagent RMg(4)X possesses a
      flat Mg(4) unit rather than a tetrahedral geometry. Our calculations further
      reveal that the radical pathway (T4) is prevalent on Mg, Mg(2) and Mg(n) clusters
      of small size, while the no-radical pathway (T2), which starts at Mg(4), becomes
      competitive with T4 as the cluster size increases. A structure-reactivity
      relationship between barrier heights and ionization potentials of Mg(n) is
      established. These findings not only resolve controversy in experiment and
      theory, but also provide insights which can be used in the design of effective
      synthesis approaches for the preparation of chiral Grignard reagents.

PMID- 23132378
TI  - Curvature effects on electronic properties of armchair graphene nanoribbons
      without passivation.
AB  - The geometric and electronic properties of curved armchair graphene nanoribbons
      without hydrogen atoms are investigated by first-principles calculations. The
      edge-atom bond length and ground state energy dramatically vary with the arc
      angle. The zipping or unzipping requirements for energy, arc angle, and
      interaction distance depend on the ribbon width. The increasing curvatures lead
      to drastic changes in electronic structures, such as energy gaps, energy
      dispersions, band-edge states, band mixing, band overlap and state degeneracy.
      There exist semiconductor-metal transitions during the variation of curvature.
      These are associated with the contribution of the edge atoms, the competition
      between the pi and sigma bonds, and hybridization of the 2p(y) and 2p(z)
      orbitals. The main features of the energy bands dominate the frequency, height,
      number, and structure of the prominent peaks in the density of states. The
      predicted results could be examined by experimental measurements.

PMID- 23132379
TI  - Transition metal oxide and graphene nanocomposites for high-performance
      electrochemical capacitors.
AB  - A method for producing nanocomposites of transition metal oxides A(3)O(4) (where
      A represents Mn, Fe or Co) and graphene nanosheets (GNS) is presented. The
      reduction of graphene oxide (GO) and the formation of A(3)O(4) nanoparticles
      (NPs) were carried out simultaneously during the reaction. The electrochemical
      properties of A(3)O(4)-GNS nanocomposites as electrode materials for
      supercapacitors are investigated by cyclic voltammetry and galvanostatic charge
      discharge tests. The as-prepared Mn(3)O(4)-GNS, Fe(3)O(4)-GNS and Co(3)O(4)-GNS
      nanocomposites exhibit large specific capacitance (708, 358 and 240 F g(-1),
      respectively), high energy density (20, 10 and 7 W h kg(-1), respectively) and
      good electrochemical stability (retention of 73%, 67.8% and 95.8%, respectively,
      after 1000 charge-discharge cycles). The excellent electrochemical performance of
      the A(3)O(4)-graphene nanocomposites indicates great potential in the application
      in commercial supercapacitors.

PMID- 23132380
TI  - The spindle-assembly checkpoint and the beauty of self-destruction.

PMID- 23132381
TI  - New functions for DNA modifications by TET-JBP.

PMID- 23132382
TI  - Asymmetrically modified nucleosomes expand the histone code.

PMID- 23132387
TI  - Segregation of polymers in confined spaces.
AB  - We investigate the motion of two overlapping polymers confined in a 2D box. A
      statistical model is constructed using blob-free-energy arguments. We find
      spontaneous segregation under the condition L > R([parallel]), and mixing under L
      < R([parallel]), where L is the length of the box and R([parallel]) is the
      polymer extension in an infinite slit. The segregation time (tau) is determined
      by solving a mean first-passage time problem and by performing Monte Carlo
      simulations. Both show a minimum in tau as a function of L. Although our results
      are restricted to 2D, the basic mechanism of competition between entropy and
      confinement leading to the minimum is suggestive of an evolutionary driving force
      for size selection.

PMID- 23132386
TI  - Cis-acting noncoding RNAs: friends and foes.
AB  - In recent years, the number and types of known functional noncoding RNAs have
      increased considerably. A subset of both short- and long-sized species are known
      to be involved in the cis regulation of target genes located at or near the same
      genomic locus. Their expression is often coordinated with that of neighboring
      protein-coding genes, and in many cases, related transcripts can influence each
      other at one step or another during their biogenesis. Here, we review the current
      literature, summarizing the existing knowledge about mammalian cis-acting RNAs
      and their impact on physiological and disease states.

PMID- 23132388
TI  - Cerebrovascular autoregulation: lessons learned from spaceflight research.
AB  - This review summarizes our current understanding of cerebral blood flow
      regulation with exposure to microgravity, outlines potential mechanisms
      associated with post-flight orthostatic intolerance, and proposes future
      directions for research and linkages with cerebrovascular disorders found in the
      general population. It encompasses research from cellular mechanisms (e.g. hind
      limb suspension: tissue, animal studies) to whole body analysis with respect to
      understanding human responses using space analogue studies (bed rest, parabolic
      flight) as well as data collected before, during, and after spaceflight. Recent
      evidence indicates that cerebrovascular autoregulation may be impaired in some
      astronauts leading to increased susceptibility to syncope upon return to a
      gravitational environment. The proposed review not only provides insights into
      the mechanisms of post-flight orthostatic intolerance, but also increases our
      understanding of the mechanisms associated with pathophysiological conditions
      (e.g. unexplained syncope) with clinical applications in relation to postural
      hypotension or intradialytic hypotension. 

PMID- 23132390
TI  - Routine use of precontrast and delayed acquisitions in abdominal CT: time for
      change.
AB  - OBJECTIVE: With major efforts being made to reduce radiation exposure in CT, one
      area of practice that requires additional improvement is limiting the number of
      acquisitions for body CT imaging. This review article defines best MDCT practice
      in terms of tailored abdominal CT protocols, designed to maximize lesion
      detection while limiting radiation exposure. CONCLUSIONS: The literature defines
      optimal acquisitions for a range of abdominal CT indications, with precontrast
      and delayed acquisitions being least commonly indicated.

PMID- 23132389
TI  - Universal pattern and diverse strengths of successive synonymous codon bias in
      three domains of life, particularly among prokaryotic genomes.
AB  - There has been significant progress in understanding the process of protein
      translation in recent years. One of the best examples is the discovery of usage
      bias in successive synonymous codons and its role in eukaryotic translation
      efficiency. We observed here a similar type of bias in the other two life
      domains, bacteria and archaea, although the bias strength was much smaller than
      in eukaryotes. Among 136 prokaryotic genomes, 98 were found to have significant
      bias from random use of successive synonymous codons with Z scores larger than
      three. Furthermore, significantly different bias strengths were found between
      prokaryotes grouped by various genomic or biochemical characteristics.
      Interestingly, the bias strength measured by a general Z score could be fitted
      well (R = 0.83, P < 10(-15)) by three genomic variables: genome size, G + C
      content, and tRNA gene number based on multiple linear regression. A different
      distribution of synonymous codon pairs between protein-coding genes and
      intergenic sequences suggests that bias is caused by translation selection. The
      present results indicate that protein translation is tuned by codon (pair) usage,
      and the intensity of the regulation is associated with genome size, tRNA gene
      number, and G + C content.

PMID- 23132391
TI  - Concomitant oral tyrosine kinase inhibitors and bisphosphonates in advanced renal
      cell carcinoma with bone metastases.
AB  - BACKGROUND: The presence of bone metastases in patients with metastatic renal
      cell carcinoma treated with oral tyrosine kinase inhibitors (TKIs) is associated
      with poorer outcome as compared with patients without bone involvement.
      Concomitant bisphosphonates could probably improve outcomes but also induce
      osteonecrosis of the jaw (ONJ). METHODS: Retrospective study on all the renal
      cell carcinoma patients with bone metastases treated with sunitinib or sorafenib
      between November 2005 and June 2012 at the University Hospitals Leuven and AZ
      Groeninge in Kortrijk. RESULTS: Seventy-six patients were included in the outcome
      analysis: 49 treated with concomitant bisphosphonates, 27 with TKI alone. Both
      groups were well balanced in terms of prognostic and predictive markers. Response
      rate (38% vs 16% partial responses, P=0.028), median progression-free survival
      (7.0 vs 4.0 months, P=0.0011) and median overall survival (17.0 vs 7.0 months,
      P=0.022) were significantly better in patients receiving bisphosphonates. The
      incidence of ONJ was 10% in patients treated with TKI and bisphosphonates.
      CONCLUSION: Concomitant use of bisphosphonates and TKI in renal cell carcinoma
      patients with bone involvement probably improves treatment efficacy, to be
      confirmed by prospective studies, but is associated with a high incidence of ONJ.

PMID- 23132392
TI  - Somatic MED12 mutations in uterine leiomyosarcoma and colorectal cancer.
AB  - BACKGROUND: Mediator complex participates in transcriptional regulation by
      connecting regulatory DNA sequences to the RNA polymerase II initiation complex.
      Recently, we discovered through exome sequencing that as many as 70% of uterine
      leiomyomas harbour specific mutations in exon 2 of mediator complex subunit 12
      (MED12). In this work, we examined the role of MED12 exon 2 mutations in other
      tumour types. METHODS: The frequency of MED12 exon 2 mutations was analysed in
      altogether 1158 tumours by direct sequencing. The tumour spectrum included
      mesenchymal tumours (extrauterine leiomyomas, endometrial polyps, lipomas,
      uterine leiomyosarcomas, other sarcomas, gastro-intestinal stromal tumours),
      hormone-dependent tumours (breast and ovarian cancers), haematological
      malignancies (acute myeloid leukaemias, acute lymphoid leukaemias,
      myeloproliferative neoplasms), and tumours associated with abnormal Wnt
      signalling (colorectal cancers (CRC)). RESULTS: Five somatic alterations were
      observed: three in uterine leiomyosarcomas (3/41, 7%; Gly44Ser, Ala38_Leu39ins7,
      Glu35_Leu36delinsVal), and two in CRC (2/392, 0.5%; Gly44Cys, Ala67Val).
      CONCLUSION: Somatic MED12 exon 2 mutations were observed in uterine
      leiomyosarcomas, suggesting that a subgroup of these malignant tumours may
      develop from a leiomyoma precursor. Mutations in CRC samples indicate that MED12
      may, albeit rarely, contribute to CRC tumorigenesis.

PMID- 23132394
TI  - Clinical equipoise regarding glycemic control: a survey of pediatric intensivist
      perceptions.
AB  - OBJECTIVES: To assess the willingness of pediatric intensivists to conduct a
      pediatric trial of blood glucose control, and to determine if self-reported
      practices were influenced by adult-specific data over the past 4 yrs. This was a
      follow-up to our previous 2005 survey. DESIGN: Electronic survey comprising a 30
      item questionnaire. SETTING: North American PICUs that were members of, or
      connected to, the Pediatric Acute Lung Injury and Sepsis Network (n = 96 targeted
      institutions). PARTICIPANTS: North American pediatric intensivists (n = 209).
      INTERVENTIONS: None. METHODS: We conducted a survey of North American PICUs using
      a Web-based questionnaire. Invitations were sent to 96 institutions in 37
      states/provinces. RESULTS: Response rate was 68% (141/209). The median
      definitions of hyperglycemia (150 mg/dL) and hypoglycemia (<=60 mg/dL) were
      similar to our 2005 survey results. Self-reported practice patterns remain
      variable. Although 75% of clinician respondents denied a change in clinical
      practice based on the published literature, the preferred blood glucose target
      range increased from 80-110 mg/dL in 2005 to 90-140 mg/dL in 2009. Intensivists
      who preferred a blood glucose target of 80-110 mg/dL decreased from 43% to 6% (p
      < 0.001). Many respondents (45%) indicated that the acceptable severe
      hypoglycemia rate (% patients) for a protocol was <=2.5%. The majority (93%)
      indicated they would be willing to enroll patients in a pediatric trial of blood
      glucose control. CONCLUSIONS: Pediatric intensivists report that they control
      blood glucose with insulin in critically ill children and do not necessarily
      adopt adult-specific data or a single uniform blood glucose target. The published
      evidence does not adequately address PICU clinicians concerns. Unanswered
      questions and persistent variation in practice suggest a need for a multicenter
      clinical trial of blood glucose control in critically ill children.

PMID- 23132395
TI  - Pharmacology of milrinone in neonates with persistent pulmonary hypertension of
      the newborn and suboptimal response to inhaled nitric oxide.
AB  - OBJECTIVES: Persistent pulmonary hypertension of the newborn is a common problem
      with significant morbidity and mortality. Inhaled nitric oxide is the standard
      care, but up to 40% of neonates are nonresponders. Milrinone is a
      phosphodiesterase III inhibitor which increases the bioavailability of cyclic
      adenosine monophosphate and has been shown to improve pulmonary hemodynamics in
      animal experimental models. The primary objective was to investigate the
      pharmacological profile of milrinone in persistent pulmonary hypertension of the
      newborn. Secondary objectives were to delineate short-term outcomes and safety
      profile. SUBJECTS AND METHODS: An open label study of milrinone in neonates with
      persistent pulmonary hypertension of the newborn was conducted. Patients received
      an intravenous loading dose of milrinone (50 MUg/kg) over 60 mins followed by a
      maintenance infusion (0.33-0.99 MUg/kg/min) for 24-72 hrs. Physiologic indices of
      cardiorespiratory stability and details of cointerventions were recorded. Serial
      blood milrinone levels were collected after the bolus, following initiation of
      the maintenance infusion to determine steady state levels, and following
      discontinuation of the drug to determine clearance. Echocardiography was
      performed before and after (1, 12 hrs) milrinone initiation. INTERVENTIONS:
      Milrinone. MEASUREMENTS AND MAIN RESULTS: Eleven neonates with a diagnosis of
      persistent pulmonary hypertension of the newborn who met eligibility criteria
      were studied. The median (SD) gestational age and weight at birth were 39.2 +/-
      1.3 wks and 3481 +/- 603 g. The mean (+/- sd) half-life, total body clearance,
      volume of distribution, and steady state concentration of milrinone were 4.1 +/-
      1.1 hrs, 0.11 +/- 0.01 L/kg/hr, 0.56 +/- 0.19 L/kg, and 290.9 +/- 77.7 ng/mL. The
      initiation of milrinone led to an improvement in PaO2 (p = 0.002) and a sustained
      reduction in FIO2 (p < 0.001), oxygenation index (p < 0.001), mean airway
      pressure (p = 0.03), and inhaled nitric oxide dose (p < 0.001). Although a
      transient reduction in systolic arterial pressure (p < 0.001) was seen following
      the bolus, there was overall improvement in base deficit (p = 0.01) and plasma
      lactate (p = 0.04) with a trend towards lower inotrope score. Serial
      echocardiography revealed lower pulmonary artery pressure, improved right and
      left ventricular output, and reduced bidirectional or right-left shunting (p <
      0.05) after milrinone treatment. CONCLUSIONS: The pharmacokinetics of milrinone
      in persistent pulmonary hypertension of the newborn is consistent with published
      data. The administration of intravenous milrinone led to better oxygenation and
      improvements in pulmonary and systemic hemodynamics in patients with suboptimal
      response to inhaled nitric oxide. These data support the need for a randomized
      controlled trial in neonates.

PMID- 23132397
TI  - The efficacy of noninvasive hemoglobin measurement by pulse CO-oximetry in
      neonates.
AB  - OBJECTIVE: To evaluate clinical applicability of noninvasive hemoglobin (Hb)
      measurement with a pulse CO-oximeter in neonates. DESIGN: Prospective comparison
      study. SETTING: Neonatal ICU. PATIENTS: Fifty-six preterm and term infants with
      median age = 20 days (range = 1-98 days) and median weight = 1,440 g (range = 530
      4,230 g). INTERVENTIONS: Hb measurements by Pulse CO-Oximetry (Masimo Radical-7)
      were recorded immediately prior to venous samplings. MEASUREMENTS AND MAIN
      RESULTS: The collected data were compared with the corresponding venous Hb level
      obtained in laboratory testing, and a total of 137 data pairs were analyzed.
      Noninvasive Hb values measured with a pulse CO-oximeter were significantly
      correlated with the venous Hb levels (correlation coefficient, r = 0.758; p <
      0.001). Hb values measured with a pulse CO-oximeter were higher than those
      measured with a laboratory hematology analyzer (13.3 +/- 2.6g/dL vs. 12.5 +/-
      3.1g/dL). In terms of the agreement between the laboratory analyzer and the pulse
      CO-oximeter, 94.8% of the measurements fell within two standard deviations of the
      mean difference. CONCLUSION: Noninvasive Hb measurements with Pulse CO-Oximetry
      provide clinically acceptable accuracy, and they were significantly correlated
      with laboratory Hb measurement in neonates. In terms of the clinical
      applicability, noninvasive Hb monitoring with a pulse CO-oximeter could be useful
      in the early detection of Hb changes in neonates.

PMID- 23132396
TI  - Opioid analgesia in mechanically ventilated children: results from the
      multicenter Measuring Opioid Tolerance Induced by Fentanyl study.
AB  - OBJECTIVE: To examine the clinical factors associated with increased opioid dose
      among mechanically ventilated children in the pediatric intensive care unit.
      DESIGN: Prospective, observational study with 100% accrual of eligible patients.
      SETTING: Seven pediatric intensive care units from tertiary-care children's
      hospitals in the Collaborative Pediatric Critical Care Research Network.
      PATIENTS: Four hundred nineteen children treated with morphine or fentanyl
      infusions. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data on opioid
      use, concomitant therapy, demographic and explanatory variables were collected.
      Significant variability occurred in clinical practices, with up to 100-fold
      differences in baseline opioid doses, average daily or total doses, or peak
      infusion rates. Opioid exposure for 7 or 14 days required doubling of the daily
      opioid dose in 16% patients (95% confidence interval 12%-19%) and 20% patients
      (95% confidence interval 16%-24%), respectively. Among patients receiving opioids
      for longer than 3 days (n = 225), this occurred in 28% (95% confidence interval
      22%-33%) and 35% (95% confidence interval 29%-41%) by 7 or 14 days, respectively.
      Doubling of the opioid dose was more likely to occur following opioid infusions
      for 7 days or longer (odds ratio 7.9, 95% confidence interval 4.3-14.3; p <
      0.001) or co-therapy with midazolam (odds ratio 5.6, 95% confidence interval 2.4
      12.9; p < 0.001), and it was less likely to occur if morphine was used as the
      primary opioid (vs. fentanyl) (odds ratio 0.48, 95% confidence interval 0.25
      0.92; p = 0.03), for patients receiving higher initial doses (odds ratio 0.96,
      95% confidence interval 0.95-0.98; p < 0.001), or if patients had prior pediatric
      intensive care unit admissions (odds ratio 0.37, 95% confidence interval 0.15
      0.89; p = 0.03). CONCLUSIONS: Mechanically ventilated children require increasing
      opioid doses, often associated with prolonged opioid exposure or the need for
      additional sedation. Efforts to reduce prolonged opioid exposure and clinical
      practice variation may prevent the complications of opioid therapy.

PMID- 23132398
TI  - Brain death in Canadian PICUs: demographics, timing, and irreversibility.
AB  - OBJECTIVES: To determine any discordance between first and second brain death
      examinations and investigate the quality of brain death determination in Canadian
      PICUs. DESIGN: Multicenter retrospective chart review. SETTING: Four Canadian
      PICUs. PATIENTS: All deaths from 1999 to 2003 were screened. Patients included
      were 36 wks corrected gestation to 17 yrs old and had at least one brain death
      examination documented in the chart. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Medical records were reviewed to determine demographics, results of the
      brain death examinations, ancillary tests, and time intervals between injury
      event, fixed dilated pupils, first brain death examination, second brain death
      examination, and terminal event. Discordance between brain death examinations was
      defined as the medical conclusion documented in the chart as brain death followed
      by no brain death. Prespecified subgroups were age <1 yr vs. >= 1 yr and organ
      donor vs. nonorgan donor. Mann-Whitney-Wilcoxon and unpaired t tests compared
      time intervals between subgroups; p value <= 0.05 was considered significant. Of
      those screened, 135 of 907 (15%) met the study eligibility criteria and 110 of
      135 (81%) had at least two brain death examinations. The prevalence of
      discordance between brain death examinations was 1 of 110 (0.91%) (95% confidence
      interval <0.01%-5.5%). In those who had two apnea tests, the prevalence of
      discordance between brain death examinations was 1 of 63 (1.6%) (95% confidence
      interval <0.01%-9.3%). Twenty-five (19%) patients had only one brain death
      examination, and one of these became an organ donor without ancillary testing.
      Twenty-four (18%) patients did not have an apnea test. Of the 48 (36%) who had
      only one apnea test, 16 became organ donors without any ancillary test. Patients
      <1 yr old had a longer time interval between the first and second brain death
      examinations than those >1 yr old. CONCLUSIONS: Some brain death diagnoses were
      not based on two examinations, and some did not include an apnea test. In
      patients who had two brain death examinations, discordant results were uncommon.

PMID- 23132399
TI  - Adaptive behavior, functional outcomes, and quality of life outcomes of children
      requiring urgent ICU admission.
AB  - OBJECTIVE: To describe the adaptive behavior and functional outcomes, and health
      related quality of life of children who were urgently admitted to the ICU.
      DESIGN: Prospective observational study. SETTING: Critical Care Medicine program
      at a University-affiliated pediatric institution. PATIENTS: Urgently admitted
      patients, aged 1 month to 18 yrs. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: We evaluated children's adaptive behavior functioning with the Vineland
      Adaptive Behavior Scale-2, functional outcomes with the pediatric cerebral
      performance category and pediatric overall performance category, and health
      related quality of life with the Pediatric Quality of Life Inventory 4 and Visual
      Analogue Scale. We enrolled 91 children and 65 (71%) completed the 1-month
      assessment. Patients had a mean (SD) Vineland Adaptive Behavior Scale-2 rating of
      83.2 (+/- 24.8), considered to be moderate-low adaptive behavior functioning.
      From baseline to 1 month, pediatric cerebral performance category ratings did not
      significantly change (p = 0.59) and pediatric overall performance category
      ratings significantly improved (p = 0.03). Visual Analogue Scale ratings
      significantly worsened from baseline to 1 wk (p < 0.0001) and significantly
      improved from 1 wk to 1 month (p=0.002). At 1 month, patients had a mean (SD)
      Pediatric Quality of Life Inventory 4 rating of 52.8 (+/- 27.9) of 100, a poor
      quality of life rating. Circulatory admissions, worse pediatric cerebral
      performance category score at baseline, worse transcutaneous oxygen saturation,
      and longer cardiac compression duration were independently associated with worse
      adaptive behavior functioning. Neurological admissions, worse pediatric cerebral
      performance category score at baseline, longer ICU stay, and longer duration of
      extracorporeal membrane oxygenation were independently associated with worse
      functional outcome. Worse pediatric cerebral performance category score at
      baseline, longer ICU stay, and longer duration of extracorporeal membrane
      oxygenation were independently associated with worse health-related quality of
      life. CONCLUSIONS: Children surviving PICU have significant adaptive behavior
      functioning and functional morbidity and reduced health-related quality of life.
      Although neurologic morbidity following ICU was associated with baseline state,
      we found that resuscitation intensity and illness severity factors were
      independently associated with the development of acquired brain injury and
      reduced quality of life.

PMID- 23132400
TI  - Motion-adaptive spatio-temporal regularization for accelerated dynamic MRI.
AB  - Accelerated magnetic resonance imaging techniques reduce signal acquisition time
      by undersampling k-space. A fundamental problem in accelerated magnetic resonance
      imaging is the recovery of quality images from undersampled k-space data. Current
      state-of-the-art recovery algorithms exploit the spatial and temporal structures
      in underlying images to improve the reconstruction quality. In recent years,
      compressed sensing theory has helped formulate mathematical principles and
      conditions that ensure recovery of (structured) sparse signals from undersampled,
      incoherent measurements. In this article, a new recovery algorithm, motion
      adaptive spatio-temporal regularization, is presented that uses spatial and
      temporal structured sparsity of MR images in the compressed sensing framework to
      recover dynamic MR images from highly undersampled k-space data. In contrast to
      existing algorithms, our proposed algorithm models temporal sparsity using motion
      adaptive linear transformations between neighboring images. The efficiency of
      motion-adaptive spatio-temporal regularization is demonstrated with experiments
      on cardiac magnetic resonance imaging for a range of reduction factors. Results
      are also compared with k-t FOCUSS with motion estimation and compensation-another
      recently proposed recovery algorithm for dynamic magnetic resonance imaging. .

PMID- 23132401
TI  - Chitosan/bovine serum albumin co-micropatterns on functionalized titanium
      surfaces and their effects on osteoblasts.
AB  - Chitosan (CS)/bovine serum albumin (BSA) micropatterns were prepared on
      functionalized Ti surfaces by micro-transfer molding (MU-TM). MU-TM realized the
      spatially controlled immobilization of cells and offered a new way of studying
      the interaction between micropatterns and cells. Two kinds of micropatterns were
      produced: (1) microgrooves representing a discontinuously grooved co
      micropattern, with the rectangular CS region separated by BSA walls; (2)
      microcylinders representing a continuously interconnected co-micropattern, with
      the net-like CS region separated by BSA cylinders. A comparison of cell behaviors
      on the two types of micropatterns indicated that the shape rather than the size
      had a dominant effect on cell proliferation. The micropattern size in the same
      range of cell diameters favored cell proliferation. However, cell differentiation
      was more sensitive to the size rather than to the shape of the micropatterns. In
      conclusion, cell behavior can be regulated by micropatterns integrating different
      materials.

PMID- 23132402
TI  - Simultaneous inhibition of COX-2 and activation of PPAR-gamma resulted in the
      same level and pattern of neuroprotection as they were targeted separately.
AB  - The inflammatory response is an immune response of the body when exposed to
      internal and external stimuli. Cyclooxygenases (COX) are major inflammatory
      mediators implicated in inflammation. COX-2 is reported to be involved in
      neuroinflammation. Moreover, 15-Deoxy-D (12,14)-prostaglandin J2 (15d-PGJ2), an
      endogenous ligand of peroxisome proliferator-activated receptor gamma (PPAR
      gamma), has been demonstrated to have anti-inflammatory actions. In this study,
      we investigated whether co-therapy of a selective COX-2 inhibitor NS-398 and 15d
      PGJ2 as a PPAR-gamma ligand could exert additional neuroprotective effects in rat
      pheochromocytoma (PC12) cells. Our findings showed that 15d-PGJ2 and NS-398
      suppress the apoptotic pathway in PC12 cells exposed to H(2)O(2) by attenuation
      of the Bax/Bcl-2 ratio. This effect was mediated through PPAR-gamma, as it was
      reversed by GW9662 (a PPAR-gamma inhibitor). Also, 15d-PGJ2 and NS-398 induced
      the Nrf2 signaling pathway and decreased NF-kappaB level in a PPAR-gamma
      dependent manner. We found that coadministration of a selective COX-2 inhibitor
      and a PPAR-gamma ligand in PC12 cells has equal neuroprotective effect compared
      to their effects when used separately. Considering the higher affinity of 15d
      PGJ2 for PPAR-gamma than NS-398, it seems that the observed neuroprotection of
      this combination therapy was from 15d-PGJ2.

PMID- 23132403
TI  - Effect of postpartum practices of doing the month on Chinese women's physical and
      psychological health.
AB  - The purpose of the study was to describe Chinese women's postpartum physiological
      and psychological health and adherence to "doing-the-month" practices. A
      descriptive repeated measures design was used, with data collected at 3 days and
      6 weeks postpartum. The convenience sample consisted of 198 healthy childbearing
      women with a term birth. Maternal physical health was measured by the Six-Minute
      Walk (endurance), Chair Stand test (muscle strength), severity of physical
      symptoms, and physical health subscales of SF36v2. Maternal psychological health
      was measured by the Edinburgh Postnatal Depression scale. Adherence was measured
      by the Adherence to Doing-the-Month Practices questionnaire. Aerobic endurance
      and lower-body muscle strength improved significantly across time (p < .001) but
      remained suboptimal for maternal age. Women who delivered by Cesarean section had
      significantly poorer physical health than those who had a vaginal delivery.
      Physical functioning significantly increased, but general health and role
      limitations due to physical health significantly decreased over time. Postpartum
      physical symptoms decreased in number and severity. Depression increased over
      time (p < .001). Adherence to doing the month was negatively correlated with
      aerobic endurance and positively correlated with depression at 6 weeks (p < .05).
      These findings challenge the assumption that practices of doing the month are
      healthy for Chinese women's recovery after childbirth. Research-based evidence
      needs to be integrated into doing-the-month practices. Education of Chinese women
      and families, whether living at home or abroad, is needed about the adverse
      health effects of doing the month. Routine screening for postpartum depression is
      also advised. 

PMID- 23132405
TI  - Preparation of char from lotus seed biomass and the exploration of its dye
      removal capacity through batch and column adsorption studies.
AB  - Char was obtained from lotus seed biomass by a simple single-step acid treatment
      process. It was used as an adsorbent for the removal of malachite green dye (MG)
      from simulated dye bath effluent. The adsorbent was characterized for its surface
      morphology, surface functionalities, and zero point charge. Batch studies were
      carried out by varying the parameters such as initial aqueous pH, adsorbent
      dosage, adsorbent particle size, and initial adsorbate concentration. Langmuir
      and Freundlich isotherms were used to test the isotherm data and the Freundlich
      isotherm best fitted the data. Thermodynamic studies were carried out and the
      thermodynamic parameters such as ?G, ?H, and ?S were evaluated. Adsorption
      kinetics was carried out and the data were tested with pseudofirst-order model,
      pseudosecond-order model, and intraparticle diffusion model. Adsorption of MG was
      not solely by intraparticle diffusion but film diffusion also played a major
      role. Continuous column experiments were also conducted using microcolumn and the
      spent adsorbent was regenerated using ethanol and was repeatedly used for three
      cycles in the column to determine the reusability of the regenerated adsorbent.
      The column data were modeled with the modeling equations such as Adam-Bohart
      model, Bed Depth Service Time (BDST) model, and Yoon-Nelson model for all the
      three cycles.

PMID- 23132406
TI  - Application of a battery of biotests for the determination of leachate toxicity
      to bacteria and invertebrates from sewage sludge-amended soil.
AB  - The objective of the study was to determine the leachates toxicity from sewage
      sludge-amended soils (sandy and loamy). Samples originated from a plot experiment
      realized over a period of 29 months. Two types of soil were fertilized with
      sewage sludges at the dose of 3 % (90 t/ha). Soil samples were taken after 0, 7,
      17, and 29 months from the application of sewage sludges. Leachates were obtained
      according to the EN 12457-2 protocol. The following commercial tests were applied
      for the estimation of the toxicity: Microtox (Vibrio fischeri), Microbial assay
      for toxic risk assessment (ten bacteria and one yeast), Protoxkit F (Tetrahymena
      thermophila), Rotoxkit F (Brachionus calyciflorus), and Daphtoxkit F (Daphnia
      magna). The test organisms displayed varied toxicity with relation to the soils
      amended with sewage sludges. The toxicity of the leachates depended both on the
      soil type and on the kind of sewage sludge applied. Notable differences were also
      observed in the sensitivity of the test organisms to the presence of sewage
      sludge in the soil. The highest sensitivity was a characteristic of B.
      calyciflorus, while the lowest sensitivity to the presence of the sludges was
      revealed by the protozoa T. thermophila. Throughout the periods of the study,
      constant variations of toxicity were observed for most of the test organisms. The
      intensity as well as the range of those variations depended both on the kind of
      test organism and on the kind of sludge and soil type. In most cases, an increase
      of the toxicity of soils amended with the sewage sludges was observed after 29
      months of the experiment.

PMID- 23132407
TI  - Adaptive alterations in the fatty acids composition under induced oxidative
      stress in heavy metal-tolerant filamentous fungus Paecilomyces marquandii
      cultured in ascorbic acid presence.
AB  - The ability of the heavy metal-tolerant fungus Paecilomyces marquandii to
      modulate whole cells fatty acid composition and saturation in response to IC50 of
      Cd, Pb, Zn, Ni, and Cu was studied. Cadmium and nickel caused the most
      significant growth reduction. In the mycelia cultured with all tested metals,
      with the exception of nickel, a rise in the fatty acid unsaturation was noted.
      The fungus exposure to Pb, Cu, and Ni led to significantly higher lipid
      peroxidation. P. marquandii incubated in the presence of the tested metals
      responded with an increase in the level of linoleic acid and escalation of
      electrolyte leakage. The highest efflux of electrolytes was caused by lead. In
      these conditions, the fungus was able to bind up to 100 mg g(-1) of lead, whereas
      the content of the other metals in the mycelium was significantly lower and
      reached from 3.18 mg g(-1) (Cu) to 15.21 mg g(-1) (Zn). Additionally, it was
      shown that ascorbic acid at the concentration of 1 mM protected fungal growth and
      prevented the changes in the fatty acid composition and saturation but did not
      alleviate lipid peroxidation or affect the increased permeability of membranes
      after lead exposure. Pro-oxidant properties of ascorbic acid in the copper
      stressed cells manifested strong growth inhibition and enhanced metal
      accumulation as a result of membrane damage. Toxic metals action caused cellular
      modulations, which might contributed to P. marquandii tolerance to the studied
      metals. Moreover, these changes can enhance metal removal from contaminated
      environment.

PMID- 23132409
TI  - Past, present and future.

PMID- 23132408
TI  - Aldehyde dehydrogenase 1A1--a new mediator of resistance to temozolomide in
      glioblastoma.
AB  - Implementation of chemotherapy with the drug temozolomide increased the overall
      survival of patients with glioblastoma multiforme (GBM; WHO grade IV), in
      particular when the O(6)-methylguanine DNA methyltransferase (MGMT) promoter is
      epigenetically silenced. Nevertheless, the prognosis remains poor, and relapse in
      GBM occurs regularly. This clinical behavior seems to be due to the existence of
      a therapy-resistant subpopulation of cells that induce tumor regrowth. The
      objective of this work was to analyze the role of aldehyde dehydrogenase (ALDH)
      1A1 in mediating temozolomide resistance and its value as a predictor of clinical
      outcome in GBM patients. Nine GBM cell lines were treated with temozolomide alone
      or in combination with 4-diethylaminobenzaldehyde (DEAB), an inhibitor of
      ALDH1A1, or with ALDH1A1 short hairpin (sh)RNA. ALDH1A1 expression and MGMT
      status of 70 primary GBM patients were correlated with median survival. ALDH1A1
      overexpression predicted temozolomide resistance in vitro. Sensitivity of ALDH1A1
      positive/MGMT-positive cells to temozolomide could be restored by inhibition of
      ALDH1A1 by DEAB or by knockdown with shRNA, as indicated by increased
      cytotoxicity, reduced clonogenicity, and accumulation in the G2/M cell-cycle
      phase. The prognosis of patients with a high level of ALDH1A1 expression was poor
      compared with that of patients with low levels (P < .0001). ALDH1A1 is a new
      mediator for resistance of GBM to temozolomide and a reliable predictor of
      clinical outcome and may serve as a potential target to improve treatment of
      human GBM.

PMID- 23132410
TI  - The influence of femoral tunnel position in single-bundle ACL reconstruction on
      functional outcomes and return to sports.
AB  - PURPOSE: The purpose of this study was to radiographically investigate the
      influence of femoral tunnel placement in ACL reconstruction on early outcomes and
      return to sports due to anatomic and nonanatomic positioning. METHODS: A
      prospective study was conducted from 2008 to 2010, with 86 athletes who underwent
      ACL reconstruction between anteromedial (AM) footprint and high AM position. Knee
      functional outcomes (IKDC objective and subjective, Tegner score, and Lysholm
      scale) return to sports and complications were analyzed at 6- and 12-month follow
      up. RESULTS: At follow-up, it was observed that tunnel projection along
      Blumensaat's line was correlated with functional outcomes on Tegner scale (at 6
      and 12 months) and IKDC subjective (at 12 months). There was a significant
      difference in mean tunnel projection along Blumensaat's line when analyzing
      return to sports (73 +/- 1.4 and 79 +/- 1.7 %, respectively, for projections on
      return vs. no return to sports, p = 0.02) and complications (73 +/- 1.3 vs. 78 +/
      1.6 %, respectively, for projections on no complications vs. complications, p =
      0.03). No differences were stated on coronal view. These correlations between
      tunnel positioning on functional outcomes could not be explained by demographic
      or baseline characteristics. CONCLUSION: The clinical relevance of this study is
      that tunnel positioning along AM footprint and high AM position represented by
      tunnel projection along Blumensaat's line is associated with early return to
      sports on previous Tegner level and better functional outcome in athletes.

PMID- 23132411
TI  - Molecular epidemiology of hepatitis C virus among different groups of people in
      the province of Fujian, China.
AB  - Genotyping of hepatitis C virus (HCV) can provide valuable information for
      prognosis and treatment duration prediction. To explore the genetic diversity of
      HCV in Fujian Province, China, 112, 104 and 48 anti-HCV-positive serum samples
      were collected from volunteer blood donors, IDUs and patients, respectively, from
      Jan 2008 to Dec 2008 and were genotyped through sequence analysis, followed by
      phylogenetic analysis in the C/E1 and NS5B regions. Genotypes could be determined
      for 85.61 and 84.85 % of samples in the C/E1 and NS5B region, respectively. 6a
      was the most prevalent subtype, which accounted for 42.04 and 43.75 % in the C/E1
      and NS5B region, respectively. Mixed infection and potential recombination were
      detected in this study. Kappa tests indicated that similar results were obtained
      by two genotyping methods targeting the C/E1 and NS5B regions. The differences in
      the main prevalent subtype between the three target groups suggest diversity of
      HCV prevalence in different populations.

PMID- 23132412
TI  - Characterization of the recent outbreak of foot-and-mouth disease virus serotype
      SAT2 in Egypt.
AB  - An outbreak of foot-and-mouth disease (FMD) in Egypt affected approximately
      40,000 cattle and water buffaloes and killed more than 4,600 animals during
      February-March 2012. To investigate the etiology of the 2012 outbreak, specimens
      were collected from six governorates and analyzed using universal primers to
      amplify the 5' untranslated region (UTR) by reverse-transcription polymerase
      chain reaction. Only FMDV-SAT2 was detected, with an overall detection rate of
      80.3 %. Complete VP1- and leader-proteinase-coding sequences, obtained from three
      isolates from three different governorates, were compared with previously
      reported sequences. Phylogenetic analysis of these sequences indicated that the
      circulating viruses were homogeneous and were closely related to topotype VII.
      Importantly, the newly emerged viruses were genetically closely related to
      strains isolated from Saudi Arabia, Sudan, Eritrea and Cameroon between 2000 and
      2010, suggesting the dominant nature of this virus and underscoring the need for
      worldwide intensive surveillance to minimize its devastating consequences.

PMID- 23132413
TI  - Use of benzynes for the synthesis of heterocycles.
AB  - About two decades after Kobayashi's discovery in 1983 of a very mild way of
      generating highly reactive aryne intermediates, the synthetic community embraced
      o-(trimethylsilyl)aryl triflates as convenient and versatile aryne precursors for
      the synthesis of carbocycles and heterocycles, as well as natural products and
      pharmaceutically promising drug candidates. This review provides a comprehensive
      overview of the construction of heterocycles using Kobayashi's silylaryl triflate
      aryne precursors. It is organized according to the type of heterocycle generated.

PMID- 23132415
TI  - Final follow-up of the Multicentre Aneurysm Screening Study (MASS) randomized
      trial of abdominal aortic aneurysm screening (Br J Surg 2012; 99: 1649-1656).

PMID- 23132414
TI  - Ammonium ion binding to DNA G-quadruplexes: do electrospray mass spectra
      faithfully reflect the solution-phase species?
AB  - G-quadruplex nucleic acids can bind ammonium ions in solution, and these
      complexes can be detected by electrospray mass spectrometry (ESI-MS). However,
      because ammonium ions are volatile, the extent to which ESI-MS quantitatively
      could provide an accurate reflection of such solution-phase equilibria is
      unclear. Here we studied five G-quadruplexes having known solution-phase
      structure and ammonium ion binding constants: the bimolecular G-quadruplexes
      (dG(4)T(4)G(4))(2), (dG(4)T(3)G(4))(2), and (dG(3)T(4)G(4))(2), and the
      intramolecular G-quadruplexes dG(4)(T(4)G(4))(3) and dG(2)T(2)G(2)TGTG(2)T(2)G(2)
      (thrombin binding aptamer). We found that not all mass spectrometers are equally
      suited to reflect the solution phase species. Ion activation can occur in the
      electrospray source, or in a high-pressure traveling wave ion mobility cell. When
      the softest instrumental conditions are used, ammonium ions bound between G
      quartets, but also additional ammonium ions bound at specific sites outside the
      external G-quartets, can be observed. However, even specifically bound ammonium
      ions are in some instances too labile to be fully retained in the gas phase
      structures, and although the ammonium ion distribution observed by ESI-MS shows
      biases at specific stoichiometries, the relative abundances in solution are not
      always faithfully reflected. Ion mobility spectrometry results show that all
      inter-quartet ammonium ions are necessary to preserve the G-quadruplex fold in
      the gas phase. Ion mobility experiments, therefore, help assign the number of
      inner ammonium ions in the solution phase structure.

PMID- 23132416
TI  - Effects of hydrogen sulphide in an experimental model of renal ischaemia
      reperfusion injury.
AB  - BACKGROUND: Renal ischaemia-reperfusion injury (IRI) is a major cause of acute
      renal failure and renal transplant dysfunction. The aim of this study was to
      investigate the efficacy of the endogenous gaseous signalling molecule hydrogen
      sulphide in protecting against renal IRI. METHODS: Large White female pigs
      underwent laparotomy and cross-clamping of the left renal pedicle for 60 min.
      Animals were allocated randomly to treatment with either intravenous hydrogen
      sulphide (n = 6) or saline control (n = 6) 10 min before clamp release, and then
      underwent a right nephrectomy. Staff were blinded to treatment allocation and
      animals were recovered for 7 days. RESULTS: Hydrogen sulphide therapy resulted in
      a marked reduction in kidney injury with reduced serum creatinine levels on days
      1-5, in a reduced area under the creatinine-time curve, and a halving of the time
      to achieve a creatinine level of less than 250 umol/l, compared with the control.
      Hydrogen sulphide also preserved glomerular function, as shown by the urinary
      protein/creatinine ratio, which, compared with baseline, increased on days 1 and
      3 in the control group (mean(s.e.m.) 3.22(1.43), P = 0.016 and 2.59(1.27), P =
      0.031), but not in the treatment group (0.99(0.23), P = 0.190 and 1.06(0.44), P =
      0.110, respectively). Mean(s.e.m.) tumour necrosis factor alpha levels at 6 h
      postreperfusion increased in the control animals (56(6) versus 115(21) pg/ml; P =
      0.026), but not in the hydrogen sulphide-treated animals (61(7) versus 74(11)
      pg/ml; P = 0.460). Renal neutrophil infiltration at 30 min (myeloperoxidase
      staining) was also significantly reduced by treatment with hydrogen sulphide (P =
      0.016). CONCLUSION: Hydrogen sulphide offers a promising new approach to
      ameliorating renal IRI with potential translation into a number of clinical
      settings, including renal transplantation.

PMID- 23132417
TI  - Impact of age and co-morbidity on surgical resection rate and survival in
      patients with oesophageal and gastric cancer.
AB  - BACKGROUND: Major surgery for cancer has become safer, including for elderly
      patients with co-morbidity. The aim of this study was to investigate the
      association between patient characteristics, resection rates and survival among
      patients with oesophageal or gastric cancer. METHODS: The prospective Dutch
      population-based Eindhoven Cancer Registry for oesophagogastric cancers diagnosed
      between 1995 and 2009 was studied retrospectively for patient characteristics
      including co-morbidity. Logistic regression analysis was performed to assess the
      likelihood of resection in patients with tumour node metastasis (TNM) stage I-III
      lesions. Cox proportional hazard analysis was used to estimate hazard ratios
      (HRs) for survival. RESULTS: The database contained information on 923 patients
      with oesophageal squamous cell carcinoma, 1181 with distal oesophageal, 942 with
      cardia and 3177 with subcardia cancer. Of patients with TNM stage I-III disease,
      20.8 per cent (557 of 2680 patients) did not undergo resection. Age 70 years or
      above was associated with a lower likelihood of resection for distal oesophageal
      (odds ratio (OR) 0.24, 95 per cent confidence interval (c.i.) 0.14 to 0.41) and
      gastric (cardia: OR 0.41, 0.22 to 0.76; subcardia: OR 0.68, 0.48 to 0.97) cancer.
      The 30-day mortality rate increased with age (4.7 per cent in patients aged less
      than 70 years versus 11.9 per cent in those aged 70 years or more; P < 0.001) and
      co-morbidity (no co-morbidity, 3.6 per cent; 1 co-morbidity, 8.6 per cent; 2 or
      more co-morbidities, 11.2 per cent; P = 0.015). Surgery (compared with no
      surgery) was independently associated with better survival for all tumour types.
      After adjustment for treatment differences, age 70 years or above and presence of
      two or more co-morbidities were independently associated with poorer survival,
      especially in patients with subcardia carcinoma (age 70 years or more: HR 1.27,
      95 per cent c.i. 1.17 to 1.48; co-morbidity: HR 1.33, 1.21 to 1.62). CONCLUSION:
      Surgical compared with non-surgical treatment of oesophagogastric cancer was
      associated with better survival, but postoperative mortality was increased in
      patients of advanced age and with greater co-morbidity.

PMID- 23132418
TI  - Severity of portal hypertension and prediction of postoperative liver failure
      after liver resection in patients with Child-Pugh grade A cirrhosis.
AB  - BACKGROUND: Patients with Child-Pugh grade A cirrhosis and clinical evidence of
      portal hypertension are likely to develop posthepatectomy liver failure (PHLF).
      Whether such patients are suitable candidates for partial hepatectomy is
      controversial. This study explored the impact of portal venous pressure (PVP) on
      PHLF and the possibility of stratifying patients with Child-Pugh grade A
      cirrhosis for risk of PHLF using clinical data alone. METHODS: Between April 2009
      and May 2011, consecutive patients who underwent partial hepatectomy for
      hepatocellular carcinoma and intraoperative measurement of PVP were included in
      this prospective study. Using signs of clinically significant portal hypertension
      (CSPH), patients with Child-Pugh grade A cirrhosis were subclassified into three
      groups: no, mild and severe CSPH. Risk factors for PHLF were subjected to
      univariable and multivariable analysis, and receiver operating characteristic
      (ROC) curve analysis. RESULTS: Sixty-seven (35.3 per cent) of 190 patients
      developed PHLF, which was persistent in 12 patients (6.3 per cent). Four patients
      (2.1 per cent) died from PHLF within 3 months of surgery. Multivariable analysis
      showed both PVP and CSPH to be independent predictors of PHLF (P < 0.001). PVP
      values, incidence of PHLF and persistent PHLF were significantly higher in the
      severe CSPH group than in the other two groups (P < 0.001). Severe CSPH (odds
      ratio 27.68, P = 0.005) and a preoperative neutrophil : lymphocyte ratio (NLR) of
      2.8 or above (odds ratio 49.75, P = 0.002) were independent factors affecting the
      incidence of persistent PHLF. CONCLUSION: The severity of CSPH, corresponding to
      different PVP levels, could be used to stratify patients with Child-Pugh grade A
      cirrhosis and to predict the incidence of PHLF. Patients with severe CSPH or a
      NLR of 2.8 or above were more likely to develop persistent PHLF after partial
      hepatectomy.

PMID- 23132419
TI  - Treatment of recurrent intrahepatic cholangiocarcinoma.
AB  - BACKGROUND: The aims of this study were to evaluate risk factors for recurrence
      following hepatectomy with curative intent for intrahepatic cholangiocarcinoma
      (ICC), and predictors of survival after intrahepatic recurrence. METHODS: All
      patients with ICC who underwent liver resection between January 1997 and August
      2011 in a single centre were analysed retrospectively. Clinicopathological
      factors likely to influence recurrence and postrecurrence survival were assessed
      by univariable and multivariable analysis. RESULTS: A total of 87 patients were
      analysed. R0 resection was achieved in 65 patients (75 per cent). Eighty-three
      patients survived more than 1 month after resection. Median survival was 33
      months, with 1-, 3- and 5-year actuarial survival rates of 79, 47 and 31 per cent
      respectively. Recurrence occurred in 45 (54 per cent) of the 83 patients, most
      frequently in the liver (25 patients). Satellite nodules (odds ratio (OR) 8.17,
      95 per cent confidence interval 1.38 to 48.53; P = 0.021), hilar lymph node
      metastases (OR 5.24, 1.07 to 25.75; P = 0.041) and perineural invasion (OR 9.68,
      1.07 to 87.54; P = 0.043) were identified as independent risk factors for
      recurrence. Repeat hepatectomy (P = 0.003) and intra-arterial yttrium-90
      radiotherapy (P = 0.048) were associated with longer survival after intrahepatic
      recurrence. CONCLUSION: Satellite nodules, hilar lymph node metastases and
      perineural invasion are risk factors for recurrence following resection with
      curative intent for ICC. Repeat hepatectomy and labelled yttrium-90 radiotherapy
      may improve survival after intrahepatic recurrence.

PMID- 23132420
TI  - Comparative study of anal acoustic reflectometry and anal manometry in the
      assessment of faecal incontinence.
AB  - BACKGROUND: Anal acoustic reflectometry (AAR) is a reproducible technique
      providing a novel physiological assessment of anal sphincter function. It may
      have advantages over conventional anal manometry. The aims of this study were to
      determine the ability of AAR and anal manometry to identify changes in anal
      sphincter function in patients with faecal incontinence (FI) and to relate these
      changes to the severity of FI. METHODS: Women with FI underwent assessment with
      AAR and anal manometry. All patients completed the Vaizey FI questionnaire and
      were classified according to symptom type (urge, passive or mixed) and integrity
      of the anal sphincters. The ability of AAR and anal manometry to correlate with
      symptom severity was evaluated. AAR was compared with anal manometry in detecting
      differences in anal sphincter function between symptomatic subgroups, and
      patients with and without a sphincter defect. RESULTS: One hundred women with FI
      were included in the study. The AAR variables opening pressure, opening
      elastance, closing elastance and squeeze opening pressure correlated with symptom
      severity, whereas the manometric measurements maximum resting pressure and
      maximum squeeze pressure did not. Unlike anal manometry, AAR was able to detect
      differences in anal sphincter function between different symptomatic subgroups.
      [corrected]. An anal sphincter defect was not associated with a significant
      change in anal sphincter function determined by either AAR or anal manometry.
      CONCLUSION: In the assessment of women with FI, AAR variables correlated with
      symptom severity and could distinguish between different symptomatic subgroups.
      AAR may help to guide management in these patients.

PMID- 23132421
TI  - Vacuum and mesh-mediated fascial traction for primary closure of open abdomen in
      critically ill surgical patients (Br J Surg 2012; 99: 1725-1732).

PMID- 23132422
TI  - Experimental study on synthetic and biological mesh implantation in a
      contaminated environment.
AB  - BACKGROUND: Implantation of meshes in a contaminated environment can be
      complicated by mesh infection and adhesion formation. METHODS: The caecal
      ligation and puncture model was used to induce peritonitis in 144 rats. Seven
      commercially available meshes were implanted intraperitoneally: six non
      absorbable meshes, of which three had an absorbable coating, and one biological
      mesh. Mesh infection, intra-abdominal abscess formation, adhesion formation,
      incorporation and shrinkage were evaluated after 28 and 90 days. Histological
      examination with haematoxylin and eosin and picrosirius red staining was
      performed. RESULTS: No mesh infections occurred in Sepramesh((r)) ,
      Omyramesh((r)) and Strattice((r)) . One mesh infection occurred in Parietene((r))
      and Parietene Composite((r)) . Significantly more mesh infections were found in C
      Qur((r)) (15 of 16; P <= 0.006) and Dualmesh((r)) (7 of 15; P <= 0.035).
      Sepramesh((r)) showed a significant increase in adhesion coverage from 12.5 per
      cent at 28 days to 60.0 per cent at 90 days (P = 0.010). At 90 days there was no
      significant difference between median adhesion coverage of Parietene
      Composite((r)) (35.0 per cent), Omyramesh((r)) (42.5 per cent), Sepramesh((r))
      (60.0 per cent) and Parietene((r)) (72.5 per cent). After 90 days the adhesion
      coverage of Strattice((r)) was 5.0 per cent, and incorporation (13.4 per cent)
      was significantly poorer than for other non-infected meshes (P <= 0.009).
      Dualmesh((r)) showed shrinkage of 63 per cent after 90 days. CONCLUSION:
      Parietene Composite((r)) and Omyramesh((r)) performed well in a contaminated
      environment. Strattice((r)) had little adhesion formation and no mesh infection,
      but poor incorporation. Some synthetic meshes can be as resistant to infection as
      biological meshes.

PMID- 23132423
TI  - Non-operative management of acute cholecystitis in the elderly (Br J Surg 2012;
      99: 1254-1261).

PMID- 23132426
TI  - Limits of metastability in amorphous ices: the neutron scattering Debye-Waller
      factor.
AB  - Recently, it became clear that relaxation effects in amorphous ices play a very
      important role that has previously been overlooked. The thermodynamic history of
      amorphous samples strongly affects their transition behavior. In particular, well
      relaxed samples show higher thermal stability, thereby providing a larger window
      to investigate their glass transitions. We here present neutron scattering
      experiments using fixed elastic window scans on relaxed forms of amorphous ice,
      namely expanded high density amorphous ice (eHDA), a variant of low density
      amorphous ice (LDA-II) and hyperquenched glassy water (HGW). These amorphous ices
      are expected to be true glassy counterparts of deeply supercooled liquid water,
      therefore fast precursor dynamics of structural relaxation are expected to appear
      below the calorimetric glass transition temperature. The Debye-Waller factor
      shows a very weak sub-T(g) anomaly in some of the samples, which might be the
      signature of such fast precursor dynamics. However, we cannot find this behavior
      consistently in all samples at all reciprocal length scales of momentum transfer.

PMID- 23132427
TI  - Porous materials in catalysis: challenges for mesoporous materials.
AB  - The discovery of ordered mesoporous materials has opened great opportunities for
      new applications in heterogeneous catalysis, thanks to their hitherto
      unprecedented intrinsic structural features. Evidence shows that, however, these
      materials have not met the researchers' expectations mainly because of the severe
      limitations related to the strength of acid sites and to the thermal/hydrothermal
      stability, significantly lower than those of zeolites and due to the amorphous
      nature of the mesostructured materials. These features are highlighted in the
      first part of this review, where the peculiarities of mesostructured materials
      are compared with those of zeolite catalysts in some reactions of industrial
      interest. New synthesis strategies, especially designed for preparing materials
      with improved physico-chemical and textural properties, together with the
      catalytic features of the resulting materials, are described and discussed in the
      second part of the review.

PMID- 23132429
TI  - Using individual-muscle specific instead of across-muscle mean data halves muscle
      simulation error.
AB  - Hill-type parameter values measured in experiments on single muscles show large
      across-muscle variation. Using individual-muscle specific values instead of the
      more standard approach of across-muscle means might therefore improve muscle
      model performance. We show here that using mean values increased simulation
      normalized RMS error in all tested motor nerve stimulation paradigms in both
      isotonic and isometric conditions, doubling mean simulation error from 9 to 18
      (different at p < 0.0001). These data suggest muscle-specific measurement of Hill
      type model parameters is necessary in work requiring highly accurate muscle model
      construction. Maximum muscle force (F (max)) showed large (fourfold) across
      muscle variation. To test the role of F (max) in model performance we compared
      the errors of models using mean F (max) and muscle-specific values for the other
      model parameters, and models using muscle-specific F (max) values and mean values
      for the other model parameters. Using muscle-specific F (max) values did not
      improve model performance compared to using mean values for all parameters, but
      using muscle-specific values for all parameters but F (max) did (to an error of
      14, different from muscle-specific, mean all parameters, and mean only F (max)
      errors at p <= 0.014). Significantly improving model performance thus required
      muscle-specific values for at least a subset of parameters other than F (max),
      and best performance required muscle-specific values for this subset and F (max).
      Detailed consideration of model performance suggested that remaining model error
      likely stemmed from activation of both fast and slow motor neurons in our
      experiments and inadequate specification of model activation dynamics.

PMID- 23132430
TI  - Hill-type muscle model parameters determined from experiments on single muscles
      show large animal-to-animal variation.
AB  - Models built using mean data can represent only a very small percentage, or none,
      of the population being modeled, and produce different activity than any member
      of it. Overcoming this "averaging" pitfall requires measuring, in single
      individuals in single experiments, all of the system's defining characteristics.
      We have developed protocols that allow all the parameters in the curves used in
      typical Hill-type models (passive and active force-length, series elasticity,
      force-activation, force-velocity) to be determined from experiments on individual
      stick insect muscles (Blumel et al. 2012a). A requirement for means to not well
      represent the population is that the population shows large variation in its
      defining characteristics. We therefore used these protocols to measure extensor
      muscle defining parameters in multiple animals. Across-animal variability in
      these parameters can be very large, ranging from 1.3- to 17-fold. This large
      variation is consistent with earlier data in which extensor muscle responses to
      identical motor neuron driving showed large animal-to-animal variability (Hooper
      et al. 2006), and suggests accurate modeling of extensor muscles requires
      modeling individual-by-individual. These complete characterizations of individual
      muscles also allowed us to test for parameter correlations. Two parameter pairs
      significantly co-varied, suggesting that a simpler model could as well reproduce
      muscle response.

PMID- 23132431
TI  - Determining all parameters necessary to build Hill-type muscle models from
      experiments on single muscles.
AB  - Characterizing muscle requires measuring such properties as force-length, force
      activation, and force-velocity curves. These characterizations require large
      numbers of data points because both what type of function (e.g., linear,
      exponential, hyperbolic) best represents each property, and the values of the
      parameters in the relevant equations, need to be determined. Only a few
      properties are therefore generally measured in experiments on any one muscle, and
      complete characterizations are obtained by averaging data across a large number
      of muscles. Such averaging approaches can work well for muscles that are similar
      across individuals. However, considerable evidence indicates that large inter
      individual variation exists, at least for some muscles. This variation poses
      difficulties for across-animal averaging approaches. Methods to fully describe
      all muscle's characteristics in experiments on individual muscles would therefore
      be useful. Prior work in stick insect extensor muscle has identified what
      functions describe each of this muscle's properties and shown that these
      equations apply across animals. Characterizing these muscles on an individual-by
      individual basis therefore requires determining only the values of the parameters
      in these equations, not equation form. We present here techniques that allow
      determining all these parameter values in experiments on single muscles. This
      technique will allow us to compare parameter variation across individuals and to
      model muscles individually. Similar experiments can likely be performed on single
      muscles in other systems. This approach may thus provide a widely applicable
      method for characterizing and modeling muscles from single experiments.

PMID- 23132432
TI  - Human hand modelling: kinematics, dynamics, applications.
AB  - An overview of mathematical modelling of the human hand is given. We consider
      hand models from a specific background: rather than studying hands for surgical
      or similar goals, we target at providing a set of tools with which human grasping
      and manipulation capabilities can be studied, and hand functionality can be
      described. We do this by investigating the human hand at various levels: (1) at
      the level of kinematics, focussing on the movement of the bones of the hand, not
      taking corresponding forces into account; (2) at the musculotendon structure,
      i.e. by looking at the part of the hand generating the forces and thus inducing
      the motion; and (3) at the combination of the two, resulting in hand dynamics as
      well as the underlying neurocontrol. Our purpose is to not only provide the
      reader with an overview of current human hand modelling approaches but also to
      fill the gaps with recent results and data, thus allowing for an encompassing
      picture.

PMID- 23132433
TI  - Towards a large-scale model of patient-specific epileptic spike-wave discharges.
AB  - Clinical electroencephalographic (EEG) recordings of the transition into
      generalised epileptic seizures show a sudden onset of spike-wave dynamics from a
      low-amplitude irregular background. In addition, non-trivial and variable spatio
      temporal dynamics are widely reported in combined EEG/fMRI studies on the scale
      of the whole cortex. It is unknown whether these characteristics can be accounted
      for in a large-scale mathematical model with fixed heterogeneous long-range
      connectivities. Here, we develop a modelling framework with which to investigate
      such EEG features. We show that a neural field model composed of a few coupled
      compartments can serve as a low-dimensional prototype for the transition between
      irregular background dynamics and spike-wave activity. This prototype then serves
      as a node in a large-scale network with long-range connectivities derived from
      human diffusion-tensor imaging data. We examine multivariate properties in 42
      clinical EEG seizure recordings from 10 patients diagnosed with typical absence
      epilepsy and 50 simulated seizures from the large-scale model using 10 DTI
      connectivity sets from humans. The model can reproduce the clinical feature of
      stereotypy where seizures are more similar within a patient than between
      patients, essentially creating a patient-specific fingerprint. We propose the
      approach as a feasible technique for the investigation of patient-specific large
      scale epileptic features in space and time.

PMID- 23132434
TI  - Multi-slice myelin water imaging for practical clinical applications at 3.0 T.
AB  - Myelin water imaging is a promising, noninvasive technique for evaluating white
      matter diseases such as multiple sclerosis and other leukoencephalopathies (LE),
      and monitoring myelination in early childhood. Unfortunately, poor image quality
      and a long acquisition time are major obstacles to practical clinical
      applications. In this study, a novel postprocessing method with an efficient
      multi-slice acquisition scheme, called T2 spectrum analysis using a weighted
      regularized non-negative least squares algorithm and nonlocal mean filter
      (T2SPARC), is presented to overcome these obstacles and achieve a shorter
      acquisition time, higher image quality, and large volume coverage. In vivo
      results from healthy volunteers and a patient with LE showed that the T2SPARC
      method can generate robust and high-quality myelin water fraction maps of 10
      slices within 11 min. This method also yields some useful byproducts such as
      intra- and extracellular water fraction and long T2 tissue water fraction maps,
      which can quantify lesions in different brain diseases.

PMID- 23132435
TI  - Effect of rat serum lipoproteins on mRNA levels and amiodarone metabolism by
      cultured primary rat hepatocytes.
AB  - Hyperlipidemia can significantly increase amiodarone (AM) in vivo liver uptake
      and decrease its velocity of microsomal metabolism. Here, hepatocytes isolated
      from normolipidemic (NL) and hyperlipidemic rats were incubated with AM in the
      presence or absence of diluted NL or hyperlipidemic serum. The serum was added
      either as preincubation before drug, or concurrently with drug; incubations
      without rat serum were used as controls. The hepatocyte levels of mRNA for
      several proteins and enzymes were also measured. Disappearance of AM was seen up
      to 72 h. There was little difference between hepatocytes from NL or
      hyperlipidemic animals in intrinsic clearance (CL(int) ) of AM. The effect of
      hyperlipidemic rat serum, either before or with AM, was profound, causing a
      significant reduction in the CL(int) . Reductions were seen in mRNA for
      cytochrome P450 1A1, 3A2, and 2D1, some transporters, and low-density lipoprotein
      receptors after exposure of hepatocytes to lipoprotein-rich sera. In conclusion,
      exposure of isolated hepatocytes to hyperlipidemic serum caused decreases in AM
      CL(int) and lower mRNA levels for some proteins involved in the uptake and
      metabolism of AM. When coincubated with serum, an additional effect of increased
      binding to lipoproteins seemed to further contribute to a reduced CL of AM.

PMID- 23132437
TI  - Reply.

PMID- 23132438
TI  - Recovery evaluation of induced changes in higher order aberrations from the
      anterior surface of the cornea for different pupil sizes after cessation of
      corneal refractive therapy.
AB  - PURPOSE: To assess corneal aberration changes induced by corneal refractive
      therapy (CRT) for different pupil sizes and to examine the recovery after
      cessation of contact lens wear. METHODS: A single-center, prospective, and
      longitudinal study was performed. Thirty-four subjects who underwent CRT for 1
      year were included. High-contrast corrected distance visual acuity (CDVA),
      manifest refraction, and corneal topography were determined during the treatment
      and 1 month after the discontinuation of the treatment. Corneal aberrations were
      calculated using the Vol-CT 6.89 software. Corneal spherical aberration, Z(4,0),
      and root mean square values (RMS) for coma-like, trefoil, tetrafoil, and higher
      order aberrations (HOAs) were estimated for different pupil sizes (3-, 4-, 5-, 6
      , and 7-mm diameters). Early Treatment Diabetic Retinopathy Study charts were
      used to measure CDVA. RESULTS: The CRT treatment induced a statistically
      significant increase of all aberrations studied for all pupil diameters. RMS
      values for coma-like, trefoil, and tetrafoil aberrations and HOAs after cessation
      of contact lens wear were not statistically significantly different for any of
      the different pupil diameters studied at baseline. However, Z(4,0) significantly
      increased from baseline to 1 month after discontinuation of the CRT lens wear for
      5-, 6-, and 7-mm diameter pupils. CONCLUSIONS: Our results suggest that CRT is a
      treatment completely reversible at 1 month after cessation of contact lens wear
      in terms of CDVA, refractive error, and RMS of coma-like aberrations and HOAs for
      all pupil sizes. However, for spherical aberration, 1 month is not enough to
      recover to the baseline level.

PMID- 23132439
TI  - Characteristic quantities of corneal epithelial structures in confocal laser
      scanning microscopic volume data sets.
AB  - PURPOSE: Fully automated quantification of the morphologic features of different
      epithelial cell layers in healthy human corneas. METHODS: In vivo confocal laser
      scanning microscopy was performed on the unilateral eyes of 6 healthy volunteers.
      Stacks of 160 images (400 * 400 MUm) with an interslice distance of 0.4 MUm were
      used to generate full thickness volume data sets of the epithelium. Size and
      shape factors of basal (BC) and intermediate cell (IC) layers were quantified
      using appropriate image analysis algorithms. Evaluated parameters include mean
      area, compactness, solidity, major and minor diameter, and maximum boundary
      distance. RESULTS: Mean area of BC and IC demonstrated a linear increase from 80
      to 160 MUm2. A similar trend was noted with major and minor diameter and maximum
      boundary distance. Major diameters of BC and IC measured between 13.2 and 17.0
      MUm, whereas minor diameter of these cells measured between 8.6 and 12.4 MUm. The
      maximum boundary distance of BC and IC ranged from 7.0 to 9.1 MUm. Compactness of
      epithelial cells clustered around 1.45 and 1.5, whereas cell solidity measured
      between 1.0 and 1.03. CONCLUSION: Several characteristic morphologic quantities
      can be calculated using this methodology without manual intervention. Our study
      demonstrated promising results and suggests that this fully automated morphologic
      quantification can be successfully applied to assess microstructural changes of
      the epithelium in normal and various corneal disorders.

PMID- 23132440
TI  - Prolonged impairment of corneal innervation after exposure to sulfur mustard and
      its relation to the development of delayed limbal stem cell deficiency.
AB  - PURPOSE: Ocular injuries after exposure to the vesicant sulfur mustard (SM) are
      characterized by acute corneal erosions and inflammation of the anterior segment
      that may be followed by delayed limbal stem cell deficiency (LSCD), expressed
      clinically by corneal neovascularization and epithelial defects. The present
      study aimed to investigate the involvement of corneal nerves in the development
      of the delayed LSCD. METHODS: Rabbit eyes were exposed to SM vapor and observed
      clinically up to 1 month. Morphology and density of corneal nerves were studied
      in acetylcholinesterase-stained whole-mount corneas at different time points
      after exposure. Corneal calcitonin gene-related peptide (CGRP) was measured and
      the relation to clinical symptoms was tested. RESULTS: Degeneration of nerve
      terminals was observed a few hours after exposure simultaneously with the typical
      signs of SM ocular toxicity. Although corneal erosions healed within days, the
      nerves continued to disintegrate under a Wallerian degeneration pattern and their
      density declined significantly at 1 week in both central and peripheral corneal
      regions. Sprouting and regenerative nerve fibers were observed later in most of
      the corneas; however, healing was partial and often abnormal and was correlated
      with corneal edema. CGRP levels decreased at 24 hours and then increased
      significantly at 1 to 4 weeks, concomitant with the reinnervation process and
      development of the late injuries. CONCLUSIONS: The prolonged impairment of
      corneal nerves, together with chronic inflammation implied by edema, and abnormal
      increase in CGRP may contribute to a pathological environment for corneal
      epithelial stem cells, leading to their death and to the development of the SM
      induced delayed LSCD.

PMID- 23132441
TI  - Prognostic factors associated with the need for surgical treatments in
      acanthamoeba keratitis.
AB  - PURPOSE: The objective of this study was to assess the factors associated with
      anatomical and visual outcomes in patients presenting with Acanthamoeba keratitis
      (AK). METHODS: This is a retrospective noncomparative interventional case series
      study comprising 44 eyes from 42 patients presenting with AK, treated with
      topical hexamidine diisethionate and topical polyhexamethylene biguanide,
      monitored between 2004 and 2008. AK was confirmed by polymerase chain reaction or
      direct microscopic examination. Correlation between clinical presentation and
      prognosis was assessed. Anatomical outcome was assessed according to the
      percentage of eyes requiring at least 1 surgical procedure in addition to topical
      treatment. Visual outcome was assessed by the best-corrected visual acuity at the
      end of follow-up. RESULTS: Polymerase chain reaction results were positive for
      Acanthamoeba in 40 of the 44 eyes (91%) and in 16 of the 44 eyes (36%) by direct
      microscopic examination. Confocal microscopy suggested the presence of
      Acanthamoeba in 12 of 19 eyes (63%). Amniotic membrane transplantation was
      performed in 8 eyes, penetrating keratoplasty in 4 eyes, and evisceration in 2
      eyes. The average follow-up time was 10 months. Surgical treatment was
      significantly associated (P < 0.05) with time from symptom onset to diagnosis of
      >30 days, an initial visual acuity of <=20/200, an infiltrate size of >3 mm,
      preperforating infiltrates, and corneal neovascularization. The average final
      visual acuity was 20/48 in eyes that did not require surgical treatment (n = 34)
      and 20/1702 in eyes that required at least 1 surgical procedure (n = 10; P <
      0.0001). CONCLUSIONS: Late diagnosis, low initial visual acuity, corneal
      neovascularization, large infiltrates, and preperforated infiltrates were
      associated with surgical treatment in patients presenting with AK. Surgical
      intervention was associated with worse visual outcome.

PMID- 23132442
TI  - Textural interface opacity after descemet stripping automated endothelial
      keratoplasty: a report of 30 cases and possible etiology.
AB  - PURPOSE: Descemet stripping automated endothelial keratoplasty (DSAEK) has its
      own set of complications including interface abnormalities. This case series
      presents the largest number of patients who developed textural interface opacity
      (TIO) at the graft-host interface after DSAEK. METHODS: This is a retrospective
      multicenter case series of 30 patients from 7 institutions with the finding of
      TIO. Clinical information collected included donor preparation details, recipient
      information, and surgical technique. Clinical outcomes included best-corrected
      visual acuity and status of TIO appearance at the last follow-up visit. Slit-lamp
      photographs were analyzed and compared. RESULTS: The majority of the patients
      (73%) had a best-corrected visual acuity of 20/40 or better. Four of the donor
      tissues were prepared with a microkeratome blade with the same lot number. Six
      patients had a central interface space between host and donor stromal surfaces-
      presumed interface fluid but potentially viscoelastic. A slight majority (57%) of
      patients had improvement in the severity of TIO, with 20% noted to have a
      complete resolution of TIO (mean follow-up of 11.9 months). Two clinical types of
      TIO were seen: an elongated type and a punctate type. CONCLUSIONS: Most patients
      with TIO after DSAEK obtain good visual outcomes. TIO spontaneously improves or
      even resolves during follow-up without intervention. The etiology of this
      condition is unknown, but we propose 2 different mechanisms. The elongated type
      could be secondary to an irregular cut of the donor with the microkeratome blade.
      The punctate type may be secondary to retained viscoelastic.

PMID- 23132443
TI  - Dislocation of the donor graft to the posterior segment in Descemet stripping
      automated endothelial keratoplasty in eyes with intraocular posterior segment
      prosthetic irides.

PMID- 23132444
TI  - In vitro comparison of combination and monotherapy for the empiric and optimal
      coverage of bacterial keratitis based on incidence of infection.
AB  - PURPOSE: Cefazolin/tobramycin, cefuroxime/gentamicin, and moxifloxacin were
      compared using bacterial keratitis isolates to determine whether empiric therapy
      constituted optimal antibacterial treatment. METHODS: Based on percent incidence
      of corneal infection, 27 Staphylococcus aureus, 16 Pseudomonas aeruginosa, 10
      Serratia marcescens, 4 Moraxella lacunata, 3 Haemophilus influenzae, 9 coagulase
      negative staphylococci, 7 Streptococcus viridans, 6 Streptococcus pneumoniae, 7
      assorted Gram-positive isolates, and 11 assorted Gram-negative isolates were
      tested for minimum inhibitory concentrations to cefazolin, tobramycin,
      cefuroxime, gentamicin, and moxifloxacin using E-tests to determine
      susceptibility and potency. RESULTS: The in vitro coverage (susceptible to at
      least one antibiotic) of cefuroxime/gentamicin (97%) was statistically equal to
      cefazolin/tobramycin (93%) and moxifloxacin (92%) (P = 0.29). Double coverage
      (susceptible to both antibiotics) was equivalent (P = 0.77) for
      cefuroxime/gentamicin (42%) and cefazolin/tobramycin (40%). The susceptibilities
      of individual coverage were moxifloxacin (92%), gentamicin (89%), tobramycin
      (74%), cefazolin (58%), and cefuroxime (52%). Methicillin-resistant S. aureus was
      best covered by gentamicin 100% (9 of 9). Tobramycin was more potent (P =
      0.00001) than gentamicin for P. aeruginosa, whereas cefazolin was more potent (P
      = 0.0004) than cefuroxime for S. aureus. CONCLUSIONS: Although there seems to be
      no in vitro empiric coverage advantage between cefazolin/tobramycin,
      cefuroxime/gentamicin, and moxifloxacin monotherapy, potency differences may
      occur and optimal treatment can best be determined with laboratory studies.

PMID- 23132445
TI  - Epithelial healing and visual outcomes of patients using omega-3 oral nutritional
      supplements before and after photorefractive keratectomy: a pilot study.
AB  - PURPOSE: To investigate the effect of omega-3 oral nutritional supplementation on
      corneal reepithelialization, visual acuity, and tear stability after
      photorefractive keratectomy (PRK). METHODS: This is a prospective, randomized,
      single-blinded controlled therapeutic trial using omega-3 oral nutritional
      supplements (TheraTears Nutrition for Dry Eyes; Advanced Vision Research-Akorn,
      Ann Arbor, MI) conducted at our center. Eighteen healthy patients with refractive
      error between -1 and -8 diopters were recruited and had bilateral PRK. The
      treatment group (n = 9 subjects) received omega-3 2 weeks before surgery through
      1 month after PRK. The control group (n = 9 subjects) was not given omega-3.
      Epithelial defects were photographed on postoperative days 0 to 5.
      Reepithelialization (area in square millimeters) was assessed by fluorescein
      staining until healing. Tear breakup time (TBUT) and uncorrected distance visual
      acuity were measured at 1 week, and 1 and 3 months postoperatively. RESULTS:
      Epithelial defect in the treatment group eyes healed faster compared with that of
      the controls (P = 0.04). The treatment group eyes healed at an average rate of
      1.19% [SD = 0.002; 95% confidence interval (CI), 1.04%-1.34%] per hour, versus
      0.83% (SD = 0.0008; 95% CI, 0.77%-0.89%) for controls (Mann-Whitney rank-sum
      test, P < 0.001). The treatment group eyes maintained a significantly longer TBUT
      from week 1 through 3 months (mean = 9.52 seconds, SD = 0.81; 95% CI, 8.93
      10.10), compared with the controls (mean = 5.52 seconds, SD = 0.81; 95% CI, 4.93
      6.10; P < 0.001), and all reached 20/20 vision versus only 4 in the control group
      1 month after surgery (P = 0.03). CONCLUSIONS: Omega-3 oral nutritional
      supplements decreased the average time for epithelial healing, and improved TBUT
      and visual acuity recovery in PRK. These findings suggested that omega-3 oral
      nutritional supplementation may be a beneficial adjunct therapy for PRK patients.

PMID- 23132446
TI  - Irregularity of the posterior corneal surface after curved interface femtosecond
      laser-assisted versus microkeratome-assisted descemet stripping automated
      endothelial keratoplasty.
AB  - PURPOSE: During donor tissue preparation for Descemet stripping automated
      endothelial keratoplasty (DSAEK), either microkeratome or femtosecond laser can
      be used for intrastromal cutting. We compared morphological and functional
      outcomes after DSAEK using both cutting techniques. METHODS: In this
      retrospective study, 22 uneventful DSAEK surgeries were reviewed. Eight donor
      corneas were prepared for DSAEK using the VisuMax femtosecond laser (Carl Zeiss
      Meditec AG, Jena, Germany). Fourteen corneas were processed using an Amadeus II
      microkeratome (Ziemer Ophthalmic Systems AG, Port, Switzerland). The
      postoperative best spectacle-corrected visual acuity was measured. Furthermore,
      corneal optical coherence tomography scans (RTVue; Optovue, Fremont, CA) were
      conducted and analyzed for graft cornea thickness and posterior surface
      irregularities using regression analysis (SPSS; IBM, Chicago, IL) on a second
      order polynomial curve as a model for the posterior surface. RESULTS: The graft
      thickness was 166.3 +/- 58.2 MUm (mean +/- SD) in the femtosecond laser group and
      172.7 +/- 48.2 MUm in the microkeratome group. The best-corrected visual acuity
      of 0.48 +/- 0.20 (logarithm of the minimum angle of resolution) in the
      femtosecond laser group was significantly poorer when compared with 0.33 +/- 0.11
      in the microkeratome group (P = 0.038). Moreover, the root mean square error
      between the posterior corneal surface and an ideal parabola surface was
      significantly higher in the femtosecond laser group (9.9 +/- 2.2 MUm) than in the
      microkeratome group (5.7 +/- 2.2 MUm; P < 0.001). CONCLUSIONS: Our study
      underlines the current superiority of a microkeratome-assisted preparation of the
      stromal-endothelial lamella before DSAEK surgery compared with the curved
      interface femtosecond laser-assisted processing.

PMID- 23132447
TI  - Treatment of mucous membrane pemphigoid with mycophenolate mofetil.
AB  - PURPOSE: To evaluate the clinical outcomes of mycophenolate mofetil (MMF)
      treatment of mucous membrane pemphigoid (MMP). METHODS: This is a retrospective
      analysis of consecutive patients with clinical MMP seen in the Ocular Surface
      Disease Clinic at the Wills Eye Institute, between January 1, 2004, and December
      31, 2010, treated with MMF. The main outcomes measured were control of
      inflammation and discontinuation of MMF. RESULTS: A total of 23 MMP patients
      taking MMF were identified. The median age of the MMF-treated patients was 77.0
      years. Eleven of the 23 patients (47.8%) had biopsy-proven MMP. All patients were
      at least Foster grading system stage 2, with most stage 3 or 4. Eight patients
      (34.8%) failed previous treatments with dapsone, methotrexate, prednisone,
      azathioprine, cyclophosphamide, or 6-mercaptopurine. The average duration of MMF
      treatment was 23.32 +/- 33.17 months (range 1-124.83 months, median 7.4 months).
      Of the 23 patients with MMP, control of inflammation was achieved with MMF within
      3 months for 56.5% [95% confidence interval (CI) 54.5-59.6], within 6 months for
      69.6% (95% CI 65.2-76.6), and within 12 months for 82.6% (95% CI 75.3-92.4) of
      the patients. Nineteen patients (82.4%) achieved control of inflammation, with 16
      of the 19 (84.2%) achieving control of inflammation with MMF as monotherapy.
      Fifteen patients were treated with MMF as initial therapy. Twenty-one percent of
      patients (5 of 23) were taken off MMF for failure of inflammatory control (4) or
      an allergic reaction (1). CONCLUSIONS: Treatment of MMP with MMF in this
      uncontrolled case series resulted in control of inflammation in the majority of
      patients with minimal side effects. Our data support consideration of MMF as an
      initial treatment option for active ocular MMP.

PMID- 23132448
TI  - Changes in corneal endothelial cell profile measurements after deep anterior
      lamellar keratoplasty for keratoconus.
AB  - PURPOSE: The primary objective was to evaluate whether postoperative alterations
      in corneal shape (as reflected by keratometry values) affect endothelial cell
      profile measurements after deep anterior lamellar keratoplasty (DALK) in a group
      of patients with keratoconus. Secondary objective was to describe the pattern of
      changes in corneal endothelial cell profile measurements during the first 3 years
      after DALK. METHODS: In this prospective interventional case series, we enrolled
      patients who had significant keratoconus and were scheduled for DALK (Melles
      technique). Cases with concomitant intraocular surgeries, intra-/postoperative
      complications, and poor quality of images were excluded. RESULTS: Two hundred one
      eyes and 45 eyes (of the original 201) were enrolled for evaluating the primary
      and the secondary objectives, respectively. At 3 months post DALK, the mean
      endothelial cell density (ECD) had significantly increased and the mean cell area
      had decreased compared with preoperative measurements (2721 vs. 2823 cells/mm2, P
      = 0.015; and 378 vs. 362 MUm2, P = 0.005, respectively). Regression analysis
      revealed a weak but significant nonlinear association between changes in mean
      keratometry and ECD changes at 3 months (R2 = 0.039, P = 0.02). Standard
      deviation of mean cell area had significantly decreased at 12 months after DALK
      compared with measurements taken at 3 months after surgery (P = 0.023) and
      remained stable thereafter. CONCLUSIONS: Apparent measurements of ECD may not
      show a decrease but instead even a slight increase in some cases after
      uncomplicated DALK (Melles technique) for keratoconus. This finding along with a
      later decrease in standard deviation of mean cell area suggests that notable
      postoperative changes in corneal biomechanical forces may affect endothelial cell
      profile measurements.

PMID- 23132449
TI  - Party foam-induced eye injuries and the power of media intervention.
AB  - PURPOSE: To describe the clinical features and treatment outcome of eye injuries
      sustained as a result of contact with artificial snow spray ("party foam"/"silly
      string") during 2 consecutive Israeli Independence Day celebrations. DESIGN:
      Retrospective, multicenter, consecutive case series. SETTING: Institutional.
      INTERVENTION/STUDY POPULATION: All patients who presented to 2 ophthalmology
      emergency services in 2007 and in 2008 with eye injury caused by contact with the
      foam. The medical records of the foam-induced eye injury cases were retrieved and
      analyzed. Data on injury type, comprehensive ophthalmic examination, and time to
      resolution were collected and analyzed. MAIN OUTCOME MEASURES: The assessed
      variables included the number of cases per year, injury type, visual acuity,
      treatment, and outcome. RESULTS: A total of 96 patients (135 eyes) had suffered
      from foam-induced ocular chemical injuries during the 2 celebrations. Sex and
      laterality were evenly distributed in the study population. The mean +/- SD age
      was 12.8 +/- 2.14 years (range, 7-17 years). All patients suffered from chemical
      conjunctivitis (100%) and superficial punctate keratopathy (79%), corneal erosion
      (27%), and conjunctival erosion (5%). More patients were seen during 2007
      compared with 2008 [85 (117 eyes) and 11 (18 eyes), respectively]. This reduction
      was directly attributable to increased public awareness because of media coverage
      (newspapers, radio, and national TV). CONCLUSIONS: Sprayed foam used in parties
      and public celebrations can cause mild-to-severe ocular surface injuries.
      Increased public awareness will inevitably reduce the use of this dangerous
      agent, but warnings need to be repeated yearly in the national media.

PMID- 23132450
TI  - Epithelium-off corneal collagen cross-linking versus transepithelial cross
      linking for pediatric keratoconus.
AB  - PURPOSE: To compare efficiency and safety of epithelium-off corneal cross-linking
      (CXL) and transepithelial cross-linking (TE-CXL) in pediatric patients with
      progressive keratoconus. METHODS: Uncorrected and corrected visual acuity,
      corneal topography and pachymetry (Pentacam; Oculus Pentacam), and in vivo
      confocal microscopy (HRT II, Rostock Cornea Module, Heidelberg Engineering,
      Heidelberg, Germany) were evaluated at baseline and at 3, 6, and 12 months.
      RESULTS: In the epithelium-off CXL group (19 patients, 23 eyes; mean age, 14.75
      +/- 2.1 years), a significant improvement at month 12 was present for Kmax [-1.11
      diopters (D), P = 0.01], Kmin (-3.2 D, P = 0.001), mean K (-1.47 D, P = 0.01),
      surface asymmetry index (-0.64 D, P = 0.001), inferior-superior symmetry index (
      0.54 D, P = 0.01), index of height asymmetry (-2.97, P = 0.03), and anterior
      elevation at the thinnest location (-2.82 D, P = 0.01) and at the apex (-2.27 D,
      P = 0.01). Postoperative corneal edema lasted 3 months in 16 eyes (69.5%) and
      more than 6 months in 2 eyes (8.7%). In the TE-CXL group (10 patients, 14 eyes;
      mean age, 15 +/- 4.2 years), a significant improvement at month 12 was present
      for Kmax (-1.14 D, P = 0.02), Kmin (-2.04 D, P = 0.01), mean K (-1.63 D, P =
      0.01), surface asymmetry index (-0.86 D, P = 0.001), inferior-superior symmetry
      index (-0.55 D, P = 0.001), index of height asymmetry (-2.95, P = 0.01), and
      anterior elevation at the thinnest location (-2.96 D, P = 0.01) and at the apex (
      2.19 D, P = 0.01). No postoperative corneal edema after TE-CXL was observed.
      Changes at month 12 from baseline were not significantly different between the 2
      groups (P > 0.05). TE-CXE was significantly less painful than epithelium-off CXL.
      CONCLUSIONS: In pediatric patients with progressive keratoconus, TE-CXL was less
      painful, provided similar effectiveness and fewer complications than epithelium
      off CXL at 12-month follow-up.

PMID- 23132451
TI  - Agreement between refractive and corneal astigmatism in pseudophakic eyes.
AB  - PURPOSE: To examine the agreement and relationship between refractive and corneal
      astigmatism in a population of pseudophakic eyes. METHODS: Patients of age at
      least 40 years, visual acuity 20/40 or better, and no ocular disease were
      included (n = 111). Refractive astigmatism was obtained by subjective refraction.
      Corneal astigmatism was measured by automated keratometry and Scheimpflug
      scanning analysis. All refractive values were converted to power vector
      components J0 and J45 for comparison and regression analysis of refractive versus
      corneal astigmatism. Main outcome measures were refractive and corneal
      astigmatism components. RESULTS: Median single Jackson cylinder (J) was similar
      in refractive [0.37 diopter (D)], keratometric (0.46 D), and Pentacam astigmatism
      (0.49 D) (P = 0.157). Median J0 astigmatic component was slightly negative,
      indicating against-the-rule (ATR) astigmatism, in refractive and Scheimpflug, but
      not in keratometric astigmatism (refractive J0: -0.10 D; keratometric J0: 0.05 D;
      Pentacam J0: -0.08 D) (P = 0.049). J45 astigmatic component was nearly zero and
      similar with the 3 methods (P = 0.416). Refractive and keratometric J0 were
      significantly correlated (r = 0.7, P < 0.01), as well as the corresponding J45
      values (r = 0.65, P < 0.01). Refractive and Pentacam astigmatic components were
      worse correlated (J0: r = 0.36, P = 0.01; J45: r = 0.45, P < 0.01). Keratometric
      and Pentacam astigmatic components were also significantly correlated (J0: r =
      0.58, P < 0.01; J45: r = 0.51, P < 0.01). CONCLUSIONS: Mean internal ATR
      astigmatism, which comes mainly from the posterior corneal surface, adds to
      anterior corneal astigmatism, resulting in ATR refractive astigmatism.
      Correlation between refractive and corneal astigmatism components is better when
      keratometric data are used.

PMID- 23132453
TI  - Modified femtosecond laser-assisted sutureless anterior lamellar keratoplasty.
AB  - A variation of the femtosecond laser-assisted sutureless anterior lamellar
      keratoplasty technique using a femtosecond laser incision for surgical management
      of anterior corneal disease is described. Six patients with corneal scars were
      treated with the laser to create a horizontal lamellar bed interface in the
      cornea of the donor and recipient eyes, with a manual partial-thickness vertical
      trephination to complete the excisions. This technique allows matching of donor
      and host tissue dimensions with precise tissue apposition and greater surface
      area for healing. No intraoperative adverse events were observed. One patient
      developed epithelial ingrowth, requiring a successful surgical intervention.

PMID- 23132452
TI  - Endothelial graft failure after contralateral autologous corneal transplantation.
AB  - PURPOSE: To report on outcomes after contralateral autologous penetrating
      keratoplasty (APK). DESIGN: Case series. PATIENT POPULATION: Five patients who
      received a contralateral APK and a simultaneous allogeneic penetrating
      keratoplasty in the donor eye at the Bascom Palmer Eye Institute and the Miami
      Veterans Affairs Hospital. RESULTS: The median patient age at the time of surgery
      in our 5 patients was 67 years (range, 58-88 years); 4 patients were male and 1
      female, and 1 patient was white and 4 were black. The surgery was uneventful in
      all cases, and no operative or immediate postoperative complications occurred in
      either eye. Follow-up time ranged from 18 to 54 months (mean, 35 months; median,
      34 months). During this time, 4 of the autologous grafts failed because of
      endothelial attenuation. Identified risk factors for failure in the autologous
      eyes included the presence of a glaucoma tube (5/5), previous graft failure
      (4/5), and anterior synechiae (2/5). CONCLUSIONS: This study is the first to
      describe graft failure because of slow endothelial attenuation after APK. This
      study underscores the importance of nonimmunologic factors in endothelial cell
      loss after corneal transplant surgery and highlights the need for further
      research to understand and modulate endothelial loss.

PMID- 23132454
TI  - Tissue microarray analysis of cyclin-dependent kinase inhibitors p21 and p16 in
      Fuchs dystrophy.
AB  - PURPOSE: To investigate the novel application of tissue microarray (TMA)
      technology to corneal disease and to report altered protein expression of
      senescence-associated cyclin-dependent kinase inhibitors p21 and p16 in Fuchs
      endothelial corneal dystrophy (FECD). METHODS: A TMA including 208 cores was
      generated from paraffin-embedded tissues, including corneal buttons of 50 FECD
      and 5 keratoconus patients retrieved after penetrating keratoplasty, 10 autopsy
      globes with nonpathologic corneas, and nonocular control specimens. TMA sections
      were immunolabeled for p21 and p16 and analyzed using a 9-grade scoring system (0
      8). Result validation was performed by immunolabeling of individual whole tissue
      sections. Corneal endothelial p21 and p16 expression levels in FECD specimens
      compared with controls served as main outcome measures. RESULTS: TMA
      immunohistochemical analysis disclosed increased endothelial expression levels of
      nuclear p21 in FECD specimens (P < 0.05) and an altered endothelial p16
      expression pattern. Immunolabeling of whole tissue sections showed statistically
      significant endothelial overexpression of both proteins (p21 and p16, P < 0.05).
      CONCLUSIONS: The present study introduces TMA technology as a valuable tool for
      molecular high-throughput profiling of corneal tissues. It demonstrates p21 and
      p16 overexpression in the corneal endothelium of genetically undifferentiated
      FECD patients supporting a role of cellular senescence in the pathogenesis of
      FECD.

PMID- 23132455
TI  - Plasma homocysteine levels in dry eye patients.
AB  - PURPOSE: To compare plasma homocysteine levels between patients with dry eye
      disease and normal control subjects. METHODS: Plasma homocysteine (enzyme
      immunoassay), vitamin B12, and folate levels were determined in 38 patients with
      dry eye and in 38 controls. RESULTS: Characteristics of the dry eye and control
      groups were similar. The mean plasma homocysteine level was 16.38 +/- 6.98
      MUmol/L in the dry eye group and 14.39 +/- 5.11 MUmol/L in the control group (P =
      0.10, t test). Hyperhomocysteinemia was present in the 43.9% of the dry eye
      patients and 33.3% of the controls (P = 0.43, chi test). There were no
      statistical differences between dry eye and control groups regarding plasma
      vitamin B12 and folate levels (P = 0.72 and P = 0.69, respectively, t test).
      CONCLUSIONS: Plasma homocysteine levels in dry eye patients may be inadequate to
      give homocysteine a role in pathogenesis. However, in ocular diseases like
      glaucoma, plasma homocysteine levels are significantly higher, and associated dry
      eye disease may cause an additional increase in plasma homocysteine levels.

PMID- 23132456
TI  - Changes of clinical manifestation of granular corneal deposits because of
      recurrent corneal erosion in granular corneal dystrophy types 1 and 2.
AB  - PURPOSE: To elucidate changes of clinical manifestation of granular corneal
      deposits after recurrent corneal erosion in granular corneal dystrophy types 1
      and 2 (GCD1 and GCD2). METHODS: Six patients (5 patients with GCD2 and 1 with
      GCD1) were included. Slit-lamp photographs of all patients and Fourier domain
      optical coherence tomography images of 3 available patients were analyzed. In
      part II of this study, to evaluate deposit disappearance incidence (becoming
      annular granular deposits), we counted deposits of another 60 GCD2 heterozygotes
      according to decade of age as the following subgroups: discoid (filled-up)
      granular deposits, annular (ring-shaped) granular deposits, and lattice-like
      lesions. RESULTS: Granular deposits dropped off singularly during recurrent
      corneal erosion in GCD2 heterozygotes, becoming annular deposits. In contrast,
      confluent granular deposits in GCD2 homozygotes and GCD1 patients dropped off in
      groups. Reaccumulation was observed at the margin of the previously dropped off
      area in patients who were followed-up for an extended period. Part II of the
      study showed that annular deposits appeared in the third decade and increased
      gradually. Discoid granular deposits increased sharply in the 40s age group, and
      lattice-like lesions increased gradually from the third decade. CONCLUSIONS: The
      disappearance of granular deposits in GCD1 and GCD2 could be interpreted as
      evidence of drop-off phenomena with recurrent corneal erosion. With drop off of
      the deposits, various configurations and morphological changes of corneal
      deposits can occur in these corneal dystrophies.

PMID- 23132457
TI  - Assessment of tear film stability in dry eye with a newly developed keratograph.
AB  - PURPOSE: To investigate the applicability of a newly developed corneal
      topographer in assessing tear film stability. METHODS: This is a prospective,
      case-control study. Forty-four Chinese dry eye patients and 41 normal subjects
      were recruited. Noninvasive tear film break-up time (NI-BUT) was measured using a
      new method based on a corneal topographer equipped with modified scan software.
      The reliability of the measurements was determined. Then, the correlations
      between the NI-BUT and the traditional fluorescein tear film break-up time,
      Schirmer I test values, and inferior tear meniscus height measurements were
      determined. The receiver operating characteristic curve technique was used to
      evaluate the NI-BUT examination in the diagnosis of dry eye. RESULTS: In total, a
      significant difference between the NI-BUT and the fluorescein tear film break-up
      time was found (3.2 +/- 2.3 seconds vs. 5.2 +/- 3.4 seconds; P < 0.001). The
      coefficient of variation and intraclass correlation coefficient values of NI-BUT
      were 12.8% and 0.93, respectively, for NI-BUT for intraobserver repeatability and
      15.4% and 0.88, respectively for interobserver repeatability. The NI-BUT showed a
      good correlation with other dry eye examinations (all P < 0.05). In addition, the
      NI-BUT was significantly shorter in dry eye patients (2.0 +/- 0.2 seconds) than
      in normal subjects (4.3 +/- 0.3 seconds; P < 0.001). When the cutoff value was
      set at <2.65 seconds, the sensitivity and specificity of the test were 84.1% and
      75.6%, respectively. CONCLUSIONS: Measurements of NI-BUT obtained with the newly
      developed corneal topographer may provide a simple, noninvasive screening test
      for dry eyes with acceptable sensitivity, specificity, and repeatability.

PMID- 23132458
TI  - Relationship of visual acuity and lamellar thickness in descemet stripping
      automated endothelial keratoplasty.
AB  - OBJECTIVES: To assess the relationship of graft thickness (GT) with visual acuity
      in patients who have undergone Descemet stripping automated endothelial
      keratoplasty (DSAEK). METHODS: We performed a retrospective chart review of all
      DSAEK patients who had anterior segment optical coherence tomography imaging.
      Donor tissue characteristics and clinical information were obtained from the eye
      bank and from the medical record, respectively. Patients with graft failure or
      with visually significant comorbidities were excluded for statistical analyses of
      the visual acuity. RESULTS: Sixty-four eyes of 52 patients with a mean follow-up
      of 27 +/- 16 months were included in the study. The mean preoperative GT of 199
      +/- 45 MUm (range, 106-303 MUm) was higher than the postoperative GT of 165 +/-
      53 MUm (range, 88-335 MUm) (P < 0.0001). There was a moderate correlation of
      preoperative GT with postoperative GT (r = 0.41; P =0.0009). Mean Snellen visual
      acuity was 20/28 at 1 year and 20/29 at the final visit (r = 0.80; P < 0.0001).
      There was a poor correlation of best-corrected visual acuity at the final visit
      with preoperative GT (r = 0.11; P = 0.57) or with postoperative GT (r = 0.26; P =
      0.16). Multivariate linear regression analysis indicates no association of either
      postoperative GT or best-corrected visual acuity at the final visit with donor
      tissue endothelial cell density, death-to-preservation time, death-to-surgery
      time, donor age, patient age, or length of postoperative follow-up. CONCLUSION:
      GT decreased after transplantation; however, there was a poor correlation of
      visual acuity with preoperative or postoperative DSAEK GT.

PMID- 23132459
TI  - Unilateral posterior stromal keratitis possibly secondary to Lyme disease.
AB  - PURPOSE: To report a case of Lyme disease presenting as unilateral posterior
      stromal keratitis in a pediatric patient. METHODS: Case report and review of
      available literature. RESULTS: A 13-year-old adolescent with unilateral painless
      blurry vision presented with prominent posterior corneal stromal haze. A positive
      Borrelia burgdorferi antibody enzyme immunoassay and Western blot analysis (9 of
      10 reactive immunoglobulin G bands and 1 of 3 immunoglobulin M bands) confirmed
      the diagnosis. Treatment with oral antibiotics and topical corticosteroids were
      necessary for resolution. CONCLUSIONS: Lyme disease may present as a unilateral
      posterior stromal keratitis, even in a pediatric population. Treatment requires
      both systemic and topical therapy.

PMID- 23132461
TI  - Long-term survival after resection of a primary leiomyosarcoma of the innominate
      vein Report of a case.
AB  - Leiomyosarcoma of the innominate vein is a rare but usually lethal disease. We
      report the case of a 50-year-old woman, undergoing a curative resection of the
      tumor. She is alive and free of disease at 88-month follow-up. Surgical excision
      remains the current optimal treatment able to provide a chance of cure. KEY
      WORDS: Late survival, Venous leiomyosarcoma.

PMID- 23132460
TI  - Immunohistochemical expression of prostate tumour overexpressed 1 (PTOV1) in
      atypical adenomatous hyperplasia (AAH) of the prostate: additional evidence
      linking (AAH) to adenocarcinoma.
AB  - BACKGROUND: Prostate tumour overexpressed 1, PTOV1, was recently identified as a
      novel gene and protein during a differential display screening for genes
      overexpressed in prostate cancer (PCa). It has been suggested that overexpression
      of PTOV1 can contribute to the proliferative status of prostate tumour cells and
      thus to their biological behaviour. METHODS: PTOV1 and Ki67 were
      immunohistochemically evaluated in PCa, atypical adenomatous hyperplasia (AAH),
      high-grade prostatic intraepithelial neoplasia (HGPIN), and normal-looking
      epithelium (NEp) of the transition zone (TZ) in 40 radical prostatectomies with
      pT2a Gleason score 6 PCa (20 with AAH and 20 with HGPIN) and in 10 simple
      prostatectomies (SPs) (5 with AAH and 5 with HGPIN). The aim was to evaluate
      PTOV1 protein expression as a marker for tumor development and progression from
      AAH to PCa. RESULTS: The proportions of PTOV1 and Ki67 positive cells increased
      from NEp through AAH and HGPIN to PCa. In particular, the mean Hscore of PTOV1
      expression in AAH was 110.90, i.e., close to three times that of NEp (40.76),
      similar to that of HGPIN (105.61) and lower than that of PCa (137.03). The mean
      values in AAH and HGPIN associated with cancer in the RPs were slightly higher
      than in the SPs. CONCLUSION: Our findings related to PTOV1 expression in AAH,
      similar to those in HGPIN, provide additional evidence linking AAH to prostatic
      adenocarcinoma.

PMID- 23132462
TI  - BMD improvements after operation for primary hyperparathyroidism.
AB  - PURPOSE: This study aims to quantify bone mineral density (BMD) changes following
      surgery in patients with primary hyperparathyroidism (PHPT) and to assess their
      relationship with clinical and biochemical variables. METHODS: A historic cohort
      of 236 PHPT patients with DXA scans pre- and 1-year postoperatively, clinical
      data, and biochemical data was analyzed. RESULTS: The mean age was 60 years
      (range 19-86) and 81 % of the patients were women. A significant postoperative
      2.6 % (95 % CI, 2.1; 3.1) increase in lumbar spine BMD was seen. The increase in
      BMD was positively associated with preoperative plasma PTH (p = 0.002), Ca(2+) (p
      < 0.001), and alkaline phosphatase (p = 0.014). Hip BMD increased 1.5 % (1.1;
      1.9). The increase in BMD was positively associated with preoperative plasma PTH
      (p = 0.005) and Ca(2+) (p < 0.001) and inversely associated with plasma
      creatinine (p = 0.004) and age (p = 0.018). Total forearm BMD did not change
      significantly (-0.2 % (-0.5; 0.1)). An increase in forearm BMD was seen in 38 %
      of all patients, and the changes were positively associated with plasma PTH (p <
      0.001) and Ca(2+) (p = 0.009). In all 91 patients with mild PHPT (plasma Ca(2+) <
      1.45 mmol/l), there was a significant postoperative increase in spine BMD (1.9 %
      (1.2; 2.7)) and in hip BMD (1.0 % (0.4; 1.6)), but not in the forearm BMD (-0.3 %
      (-0.7; 0.2)). The postoperative BMD gain was higher in the hip and forearm in
      patients operated for adenomas compared with patients treated for hyperplasia.
      CONCLUSIONS: We found significant postoperative BMD improvements both at the hip
      and the spine. BMD improvements were also significant in mild cases. At all scan
      sites, there were positive associations between preoperative plasma PTH levels
      and postoperative BMD increases. The measured BMD changes may mainly be due to a
      decrease in PTH-induced bone turnover with refilling of the remodeling space.

PMID- 23132464
TI  - Activated carbons and carbon-containing poly(vinyl alcohol) cryogels:
      characterization, protein adsorption and possibility of myoglobin clearance.
AB  - Adsorption of myoglobin (Mb), bovine serum albumin (BSA) and gamma-globulin (GG)
      onto activated carbons (ACs) with different pore size distributions, and
      poly(vinyl alcohol) (PVA) monolithic cryogels containing AC particles was
      studied. The highest initial rate of Mb adsorption was observed for AC having the
      largest specific surface area (1939 m(2) g(-1)) and pore volume (1.82 cm(3) g(
      1)). The adsorption kinetics of proteins was characterized by a bimodal shape of
      the distribution f(D) function of an effective diffusion coefficient. Adsorption
      isotherms of Mb and GG were of Freundlich type within the studied range of
      equilibrium concentrations (10-150 MUg mL(-1)). The distributions of free energy
      of protein adsorption were bimodal and reflected both interactions with carbon
      surfaces and self-association of proteins. Adsorbed amounts of Mb were the
      highest among the proteins studied (up to 700 mg g(-1) carbon), which was
      attributed to the higher fraction of pores accessible for Mb. Incorporation of
      carbon particles into PVA-based cryogel resulted in macroporous monolithic
      composite materials (AC-PVA) exhibiting good flow-through properties. Scanning
      electron microscopy of the composites showed macroporous aggregates of carbon
      particles held together by films and bridges of PVA. The rates of adsorption and
      adsorbed amounts of proteins on AC-PVA were reduced compared to the pristine
      carbon and depended on the carbon content in the composites. Nevertheless,
      adsorption of Mb on AC-PVA took place even in the presence of 500-fold higher
      concentration of BSA. This indicated a possibility of Mb clearance from blood
      plasma using the PVA-carbon monoliths.

PMID- 23132465
TI  - Epidemic of non-communicable disease and its control.

PMID- 23132463
TI  - The correlation of genome size and DNA methylation rate in metazoans.
AB  - Total DNA methylation rates are well known to vary widely between different
      metazoans. The phylogenetic distribution of this variation, however, has not been
      investigated systematically. We combine here publicly available data on
      methylcytosine content with the analysis of nucleotide compositions of genomes
      and transcriptomes of 78 metazoan species to trace the evolution of abundance and
      distribution of DNA methylation. The depletion of CpG and the associated
      enrichment of TpG and CpA dinucleotides are used to infer the intensity and
      localization of germline CpG methylation and to estimate its evolutionary
      dynamics. We observe a positive correlation of the relative methylation of CpG
      motifs with genome size. We tested this trend successfully by measuring total DNA
      methylation with LC/MS in orthopteran insects with very different genome sizes:
      house crickets, migratory locusts and meadow grasshoppers. We hypothesize that
      the observed correlation between methylation rate and genome size is due to a
      dependence of both variables from long-term effective population size and is
      driven by the accumulation of repetitive sequences that are typically methylated
      during periods of small population sizes. This process may result in generally
      methylated, large genomes such as those of jawed vertebrates. In this case, the
      emergence of a novel demethylation pathway and of novel reader proteins for
      methylcytosine may have enabled the usage of cytosine methylation for promoter
      based gene regulation. On the other hand, persistently large populations may lead
      to a compression of the genome and to the loss of the DNA methylation machinery,
      as observed, e.g., in nematodes.

PMID- 23132466
TI  - Analysis of ear, nose and throat foreign bodies in dhulikhel hospital.
AB  - BACKGROUND: Foreign body in ear nose and throat are commonly encountered by
      otolaryngologists, pediatricians and primary care physicians. OBJECTIVE: The aim
      of this study is to analyze different types of foreign bodies and
      sociodemographic correlates of self inflicted foreign body insertion in ear,
      nose, throat. METHOD: This was a two year hospital based cross sectional
      descriptive study performed in the Department of ear nose and throat (ENT),
      Dhulikhel Hospital - Kathmandu University from June 2009 to June 2011 after
      verification from the Institutional Review Committee. Using a predesigned
      questionnaire, socio-demographic data was collected prospectively by examining
      clinically all patients attending with foreign body and interviewing the
      caregivers of pediatric patients after removal of foreign body. The data
      collected from 312 patients was entered and analyzed by using descriptive and
      analytical statistical methods using SPSS version 16.0. RESULTS: The mean age was
      21.26 years with majority between 0-10 years (50.6%). Male predominance was noted
      (58.97%). Most patients or caregivers were illiterate (35.1%) or literacy up to
      primary level(21.12%).Foreign body of the ear was found to be most frequent (
      47.4%) and mostly they were non-living (96.1%). Most patients presented late
      (80%) and had history of prior attempted removal (67%). Pearsons chi square test
      between education level and duration of time was significant (p value- 0.0000).
      One way ANOVA test between type of foreign body and age was significant (p value-
      0.001). CONCLUSION: Foreign bodies are common in adult and pediatric ear, nose
      and throat. They can potentially be associated with significant complications if
      not taken care of immediately.

PMID- 23132467
TI  - Association between selected socio demographic variables and musculoskeletal
      symptoms experienced by dentists in a southern Karnataka district.
AB  - BACKGROUND: The majority of working dentists experience some type of
      musculoskeletal discomfort during the course of their professional career. The
      prevalence and location of musculoskeletal symptoms are influenced by work
      habits, postures adopted by dentists while performing their professional work and
      socio demographic variables. OBJECTIVES: The current study was carried out to
      find the association between musculoskeletal symptoms experienced by dentists and
      selected socio demographic variables in a southern Karnataka district. METHODS:
      For this study 300 dentists were selected by using convenience sampling method
      among post graduate dental students, faculty members and private practitioners
      with more than one year of experience from in and around Mangalore city. In order
      to find the association, a pre-tested, self-administered questionnaire -
      Musculoskeletal Disorder Rating Scale was used. RESULTS: The study showed that
      there was statistically significant association between frequency of pain and
      average patient(s) treated per day. The association between intensity of pain and
      average patient(s) treated per day was highly significant. Further there was a
      significant association between intensity of pain and field of dental practice.
      With regard to the field of dental practice, frequency of stiffness was
      significantly associated with the age. The association between frequency of
      stiffness and no. of year(s) in profession was highly significant. CONCLUSION:
      The study revealed a significant association between musculoskeletal symptoms
      experienced by the dentists and socio demographic variables like; age, field of
      dental practice, no. of years in profession and average patients treated per day.

PMID- 23132468
TI  - Enteric opportunistic parasitic infections among HIV seropositive patients in
      Kathmandu, Nepal.
AB  - BACKGROUND: Enteric opportunistic parasitic infections are the major source of
      diarrheal disease in developing countries mainly in Human Immunodeficiency virus
      (HIV) infected patients. OBJECTIVE: The study was to detect enteric parasites
      causing diarrhea and their association with immune status in HIV-seropositive
      patients. METHODS: The present study was conducted in Dirgh-Jeevan Health Care
      Research Center and Tribhuvan University Teaching Hospital, Public Health
      Research Laboratory, Kathmandu, Nepal between June 2010 and May 2011 involving
      146 Human Immunodeficiency virus (HIV) positive patients. Serostatus from these
      patients were detected by Enzyme Linked Immunosorbent assay. CD4+ T cell counts
      were done by flow cytometry. Stool was examined for enteric parasites by
      microscopy with special staining methods. RESULTS: A total of 146 HIV sero
      positive patients with and without diarrhea age between 20 to 45 years were
      included in the study. Of the 146 patients, the protozoan parasitic infection was
      found in 30.13% (44/146). Out of 146 patients, 78 had diarrhea in which parasitic
      infection was 39 (50%) and 7.35% (5/68) protozoal parasites positive cases did
      not have diarrhea. A significant difference (p less than 0.05) was observed in
      the level of infection of intestinal protozoan between the HIV seropositive with
      diarrhea and HIV-seropositive without diarrhea. Out of 43 patients whose CD4+ T
      cells were less than 200/MUl, 29 (67.4%) had opportunistic parasitic infection
      whereas out of 103 patients whose CD4+ T cells were =200/mcl, only 15 (14.56%)
      had opportunistic parasitic infection (P less than 0.05). CONCLUSION: Enteric
      opportunistic parasitic infections were detected in 30.1% among HIV-seropositive
      patients and low CD4+ T count indicated high enteric opportunistic infection.
      Early detection of enteric parasitic infections will help in the management and
      to improve the quality of life for HIV-infected individuals.

PMID- 23132469
TI  - Cesarean section without urethral catheterization: a randomized control trial.
AB  - BACKGROUND: Urethral catheterization is done as a routine procedure in cesarean
      section. It is associated with high incidence of urinary tract infections,
      discomfort, delayed ambulation and longer hospital stay. OBJECTIVE: To determine
      the feasibility and safety of cesarean section without urethral catheterization.
      METHODS: A prospective, randomized controlled trial was carried out from April
      2008 to March 2009, in the Department of Obstetrics and Gynecology, B. P. Koirala
      Institute of Health Sciences. Among 150 patients who had undergone cesarean
      section 75 were catheterized and 75 were uncatheterized. RESULTS: First void
      discomfort was significantly associated with the use of indwelling catheter (OR
      6.95, CI 95 %, 3.74 to 12.95; P less than 0.001).Significant number of patients
      with indwelling catheter had signs and symptoms of urinary tract infection (OR
      6,CI 95%, 2.59 to 13. 86; P less than 0.001). Positive urinalysis for urinary
      tract infection was high in catheterized group (P less than 0.001). Hospital stay
      was shorter in patients without catheter (p less than 0.05). None of the patients
      had bladder injury. There were no significant differences in duration of surgery
      and ambulation time between two groups of patients. CONCLUSIONS: Cesarean section
      can be done safely without urethral catheterization with reduced morbidities.

PMID- 23132470
TI  - Bruckner red light reflex test in a hospital setting.
AB  - BACKGROUND: Childhood blindness is a major problem in developing world including
      Nepal that needs to be addressed. OBJECTIVE: The objective of study was to
      measure the effectiveness of the Bruckner red reflex test for screening of
      posterior segment opacities in children. METHODS: Patients aged less than five
      years who came to the Tilganga Institute of Ophthalmology, Kathmandu from March
      to August, 2009 were recruited in this cross-sectional descriptive study.
      Children were screened with the Bruckner red light reflex test in a dark room.
      Patients with abnormal Bruckner tests had their eyes dilated for further
      investigations. Abnormalities were recorded. The number of patients with an
      abnormal Bruckner test was recorded and correlated with their potential
      pathology. RESULTS: A total of 172 patients with 97 boys and 75 girls were
      included. Twenty-three had abnormal Bruckner test results in either one or both
      eyes. Four of these twentythree patients had no pathology diagnosed; hence the
      sensitivity of the Bruckner screen to diagnose significant pathology was
      calculated at 82.6%. Of the 153 patients with normal results, two patients were
      found to have pathology detected, which included cataract and strabismus. Hence,
      the specificity of this test was 98.7%. The screening test had a positive
      predictive value of 90.5% and a negative predictive value of 97.4%. CONCLUSION:
      Bruckner test screening is a sensitive and specific marker for detecting the
      posterior segment opacities in children. We recommend utilizing the test to
      evaluate these problems where other technologies are rare.

PMID- 23132471
TI  - Antibiotic usage and its sensitivity pattern in the NICU.
AB  - BACKGROUND: Sepsis is a major cause of mortality and morbidity in newborns
      affecting both developed and developing countries accounting a quarter around one
      million deaths per annum. OBJECTIVE: This study was aimed to assess the
      prevalence of neonatal sepsis, culture isolates, pattern, antibiotic sensitivity
      and drug prescribing pattern. METHODS: In present prospective study, 48 neonates
      admitted in pediatric ward from January to March 2011 of Dhulikhel Hospital were
      included. The gestation age, onset of sepsis, culture isolates, antibiotic
      sensitivity pattern and drug prescribing pattern were studied. Environmental air
      sampling of NICU (Neonatal Intensive Care Unit) was done by settle plate method
      for microbial examination. RESULT: Among 48 neonates, 23 (47.92%) neonates were
      culture positive with predominant isolates of Klebsiella oxytoca 11(47.83%),
      Pseudomonas sp. 4(17.39%), Methicillin Resistant Staphylococcus Aureus (MRSA)
      3(13.04%) and single case of Enterobacter spp. In environmental samples, K.
      oxytoca and Enterobacter sp. were isolated. Amikacin, Imepeneum and Ciprofloxacin
      were sensitive whereas Ampicillin in combination with Cloxacillin, Ampicillin,
      Aztreonam were resistant for Klebsiella. oxytoca. Amikacin, Ceftazidime and
      Imipenuem were sensitive to Enterobacter spp. The single or combinations of
      resistant antibiotics were found to be prescribed. CONCLUSION: The emerging
      antibiotic resistances among the culture isolates and coherence with
      environmental samples were observed. Hence, special measures are imperative for
      reducing environmental contamination and the rational usage of antibiotics for
      preventing the infection and emerging antibiotic resistance. The study recommends
      need of the antibiotic policy to curb the present scenario.

PMID- 23132472
TI  - Morphometry of acromion process of human scapulae and its clinical importance
      amongst Nepalese population.
AB  - BACKGROUND: Morphometry of the acromion process of the scapula is an important
      factor implicated in impingement syndrome of the shoulder joint. Authors who have
      studied this process have tried to classify it according to the standard Bigliani
      classification viz., type 1, 2 and 3. OBJECTIVES: To analyze and classify the
      acromion process of human scapulae. METHODS: The present study was observational,
      cross-sectional and descriptive in nature. The present study was conducted on 68
      adult human scapulae (30 right and 38 left) of unknown age and sex in the
      Department of Anatomy, Kathmandu University School of Medical Sciences,
      Dhulikhel, Nepal. The length and breadth of the acromion process and the
      distances from the tip of the acromion process to the uppermost point of the
      glenoid cavity and to the tip of the corocoid process were measured with a help
      of caliper and measuring tape. RESULTS: The average length of acromion process on
      the right and left scapulae were 46.46 +/- 5 SD mm and 45.57 +/- 5.21 SD mm
      respectively. The average breadth of acromion process of right and left scapulae
      were 26.63 +/- 3.55 SD mm and 27.23 +/- 3.06 SD mm respectively. The acromio
      coracoid distance on the right and left side were 39.03 + 6.20 mm and 39.39 +5.32
      mm respectively. The acromio-glenoid distance was also measured which was 31.83
      +3.66 mm and 31.97 +3.96 mm on right and left side respectively. The acromion
      process was classified in the present study into 3 types, based on the shape as:
      Triangular - 36.76%, Quadrangular - 52.94% and Tubular - 10.29%. CONCLUSIONS:
      Knowing the data on the shape and various distances of acromion may not only help
      the orthopaedicians during surgical repair around the shoulder joint but also may
      be of interest to the anthropologists when studying about the evolution of the
      bipedal gait. The morphometric analysis of the acromion should be used like an
      auxiliary to promote a better knowledge about the disease that appears in this
      area.

PMID- 23132473
TI  - Knowledge of emergency management of avulsed teeth among general dentists in
      Kathmandu.
AB  - BACKGROUND: An avulsed permanent tooth is one of the most emergency situations in
      dentistry. Dentists handling the situation should have adequate knowledge in this
      field. OBJECTIVE: To assess the level of knowledge of emergency management of
      avulsed teeth among general dentists in Kathmandu. METHODS: A questionnaire
      containing 10 close ended questions about emergency management of avulsed teeth
      was distributed among 102 general dental practitioners working in different
      private dental hospitals and clinics of Kathmandu. The dental hospital and
      clinics were randomly selected. This cross sectional study was conducted between
      January 2012 to February 2012. RESULTS: Among the studied group, almost all of
      the participants, 98(96.1%) said that an avulsed permanent tooth cannot be
      replanted in all cases. Majority of them, 63 (61.8%) said that the critical time
      for the replantation is within 20 minutes. General dentists of Kathmandu did not
      have adequate knowledge about emergency management of avulsed teeth. CONCLUSION:
      An education program should be conducted to increase the knowledge of general
      dentists in the management of traumatic injuries to teeth.

PMID- 23132474
TI  - Postoperative nausea and vomiting in patients undergoing total abdominal
      hysterectomy under subarachnoid block: a randomized study of dexamethasone
      prophylaxis.
AB  - BACKGROUND: Postoperative nausea and vomiting is a common distressing problem in
      patients undergoing gynaecological surgery under anaesthesia including central
      neuraxial blockade, which requires frequent medical interventions. OBJECTIVES: We
      aimed to find out the antiemetic effect of prophylactic dexamethasone for
      prevention of postoperative nausea and vomiting in patients undergoing total
      abdominal hysterectomy under subarachnoid block. Influences of dexamethasone on
      patient satisfaction and postoperative analgesia were also observed as secondary
      objectives. METHODS: This was a prospective, randomized, double blind, placebo
      controlled study conducted in BPKIHS, from January 2009 to April 2009. This study
      involved 80 American Society of Anaesthesiologist Physical Status I and II
      patients undergoing total abdominal hysterectomy under subarachnoid block.
      Patients were divided into two groups of 40 each to receive either 4 mg of
      dexamethasone (group D) or normal saline (group N) in volume of 2 ml
      intravenously 1 hour prior to subarachnoid block. Surgery was allowed to start
      with block height of at least T8 dermatome. Intraoperative and postoperative
      nausea and vomiting was observed using nausea and vomiting scale every 4 hour for
      24 hours. RESULTS: Seven (17.4%) patients in group D and 11 (27.5%) patients in
      group N had nausea and vomiting in the intraoperative period (P=0.284). Sixteen
      (40%) patients in group D experienced nausea and vomiting in the postoperative
      period as compared to 27 (67.5%) in group N (P =0.0136). Accordingly, the mean
      requirement of rescue antiemetic was less in group D compared to Group N
      (P=0.042). Further, only 15 (37.5%) patients in group D required postoperative
      supplemental analgesic as compared to 23 (57.5%) in group N (P=0.058). After 24
      hrs of surgery, 26 (65%) patients expressed satisfaction in group D as compared
      to 16 (40.0%) in group N (P =0.025). CONCLUSIONS: Use of dexamethasone prior to
      subarachnoid block in patients undergoing total abdominal hysterectomy
      significantly reduces the incidence of nausea and vomiting and the requirement of
      antiemetic in the postoperative period, with better patient satisfaction.

PMID- 23132475
TI  - Q-Switched Neodymium-Doped Yttrium Aluminum Garnet laser therapy for pigmented
      skin lesions: efficacy and safety.
AB  - BACKGROUND: Nepalese population with Fitzpatrick skin types III-V has high
      prevalence of pigmentary disorders and it is a growing cosmetic concern. Q
      Switched Neodymium- Doped Yttrium Aluminum Garnet (QS Nd-YAG) laser is an
      efficacious tool in the treatment of pigment disorders. OBJECTIVE: To highlight
      the efficacy and safety profile of various pigment disorders. METHODS: A
      prospective study done in Dhulikhel Hospital, Kathmandu University Hospital from
      January 2009 to January 2011. Patients undergoing laser for pigmented skin
      lesions were followed for response and safety profile. We included total 270
      patients in the study with various disorders especially nevus, tattoos and
      melasma. Settings were repeated at 3-4 weeks interval and response was evaluated
      on clinical basis. Efficacy was then evaluated according to various parameters.
      RESULTS: For nevus, total 840 treatment sessions had been performed with an
      average of 6.88 sessions (range 3-11). Nd: YAG laser was very efficacious in
      removal of blue and black colored tattoos with an average of 7.9 and 9.5 sessions
      respectively. However, red mixed with blue and or green tattoos were relatively
      resistant to treatment and required average 10.33 treatment sessions. Melasma and
      freckles both responded to the therapy but recurrence rate was high. CONCLUSION:
      Our results indicate that QS Nd: YAG laser is an effective modality for pigment
      disorders among Nepalese population. Nevus and melasma respond well but
      recurrence rate of melasma is high. Blue tattoos respond well while mixed colored
      tattoos are quite resistant to Nd: YAG laser alone. Transient pain and temporary
      hyperpigmentation are common side effects.

PMID- 23132476
TI  - Perception about the role of anesthesia and anesthesiologist among the
      paramedical staffs: perspective from a medical college in Nepal.
AB  - BACKGROUND: Anesthesiologists and anesthesia has been considered behind the
      scene. The image and status of anesthesiologist in the eyes of the medical and
      lay communities has always been a problem. OBJECTIVES: This study was designed to
      assess the knowledge about the role of anesthesiologist among the paramedical
      staffs at Kathmandu University Hospital. METHODS: This prospective questionnaire
      based study was done at Kathmandu University School of Medical Science, Dhulikhel
      Hospital for 2nd January 2011 to 30th Jan 2011 among the paramedical staffs
      working in different department of the hospital. RESULTS: There were 150
      questionnaire distributed out of which 120 responded. Mean Age was 23.33 and most
      of the respondents were female with majority having education qualification
      equivalent to intermediate level. Only 49.20 said it to be a different specialty
      and 72.5% said anaesthesiologist work differently in the theatre where as 70%
      knew anaesthesiologist did something in the post-operative period too.
      CONCLUSION: Anesthesiologists have duty to visit patients pre operatively and
      post operatively. The role inside the theatre and expanding role outside the
      theatre is poorly known. The awareness about the role of anesthesiologist in
      operation theatre, in intensive care unit, acute and chronic pain management and
      emergency care areas should be highlighted to all the staffs.

PMID- 23132477
TI  - Lip prints: an identification aid.
AB  - BACKGROUND: Lip prints are the normal lines and furrows in the form of wrinkles
      and grooves present in the human lip between the inner labial mucosa and outer
      skin having certain individual characteristics like fingerprints. OBJECTIVE: The
      aim of the study was to highlight the importance of lip prints in sex
      determination related to forensic investigation for identification. METHODS:
      Study was conducted on 150 medical students which include 75 males and 75 females
      of Kathmandu University School of Medical Sciences, Dhulikhel, Kavre on 2011. Lip
      prints were collected and analyzed as per Suzuki classification. RESULTS: There
      was significant difference between male and female lip print patterns. Type II
      was most common combining both. Type I and I ' was more common in male where as
      Type I was rare in female. Type II in fourth quadrant was seen in almost all
      female and also the commonest. Similar patterns in all four quadrants were common
      findings in female. CONCLUSION: The study showed that each lip print is unique
      and the sex of the person can be predicted on the basis of patterns present in
      prints.

PMID- 23132478
TI  - Clinical and laboratory profile of children with eosinophilia at Dhulikhel
      hospital.
AB  - BACKGROUND: Eosinophilia in children is commonly caused by or parasitic, allergic
      and immunologic problems. OBJECTIVES: To study clinical and laboratory profile of
      patients with eosinophilia and to identify possible causes. METHOD: A prospective
      and descriptive study was conducted from January 2009- December 2011. All the
      cases of eosinophilia with symptoms and signs of single or multiple organ were
      included. The known cause of eosinophilia like allergy, asthma and drugs were
      excluded. RESULTS: During three years period, 84(2.41%) cases had eosinophilia
      with single or multiple organ involvement. 14.3%, 39.3% and 46.4% had mild,
      moderate and severe eosinophilia respectively, with cases of hypereosinophilia
      comprising 85.7%. Eosinophilia was seen predominantly in Tamang caste with
      overall age ranging from 1-14 years. Most common symptoms and signs were
      abdominal pain (67.9%) hepatomegaly (59.5%) respectively. Gastrointestinal system
      was most commonly involved organ followed by respiratory system. Nineteen percent
      had polyserositis involving pleural, pericardial effusion and ascites at
      presentation. Out of 84 patients only nine serum samples were able to be sent for
      parasitological analysis. Sixteen cases had identifiable and/ or possible causes.
      Serum sample for parasitological analysis revealed fascilosis, filariasis,
      strongylosis, stercoralis and toxocariasis. CONCLUSION: Eosinophilia is more
      common among Tamang population in our study. Most common symptoms and signs are
      abdominal pain and hepatomegaly respectively. Parasitic infection seems to be the
      most common cause however further study has to be done to reach final conclusion.

PMID- 23132479
TI  - Perceptions and care seeking behavior of obstetric complication in Thailand.
AB  - BACKGROUND: Importance of maternal health has been recognized over the last
      decade, however information about the perception of illness and healthcare
      behavior of obstetric complication is lacking. OBJECTIVE: This study assesses
      women ' s knowledge, perception, and experience of obstetric complication and
      care-seeking behavior and explores the factors associated with the morbidity and
      the constraints hindering them from seeking timely care. METHODS: Twenty one in
      depth interviews on the perceptions, experience and care seeking behavior related
      to pregnancy and delivery of Women at Kanchanaburi Demographic Surveillance site
      of Thailand were conducted. A structured guideline was first prepared in English
      and translated into Thai language. An interpreter was hired to interview women at
      the Thai-Myanmar border to translate Thai into local language. A moderator note
      taker, and interpreter were present throughout the interview period and tape
      recorded the conversation. RESULTS: In-depth interview revealed that even though
      quality maternal health care was accessible to most of the women, obstetric
      complication was prevalent and they were not seeking appropriate care
      specifically in highland. Too early and too late marriage, frequent child
      bearing, poverty, hard work, poor nutrition and traditional practices were the
      reasons for complications. Poor transportation, lack of health insurance,
      inadequate training of health personnel, poor health facilities and the
      perception that the complications are normal for pregnant women were the main
      reasons for not seeking appropriate care. CONCLUSIONS: Perceived reasons for
      complications among women living in Kanchanaburi, Thailand were early marriage,
      frequent childbearing, hard work, poor nutrition and traditional practices. The
      constraints hindering them from seeking care for the complications were perceived
      to be the lack of access to health personnel, health facilities, and proper
      transportation. These issues seemed to be related to poverty.

PMID- 23132480
TI  - Anticipated pain and pain experience among orthodontic patients: is there any
      difference?
AB  - BACKGROUND: Orthodontic treatment is taken as a painful procedure by most of the
      patients. The pain can be experienced during different procedures like separator
      placement, banding, bonding, extraction as well as arch wire activation and
      debonding. There are very few studies done on the anticipated pain and pain
      experienced among mentioned orthodontic procedures. OBJECTIVES: To compare the
      anticipated pain and pain experience among the patients going for comprehensive
      orthodontic treatment. METHODS: Total 45 patients going for comprehensive
      orthodontic therapy are enrolled into the study. They are given a 100mm Visual
      Analogue Scale (VAS) for pain. The anticipated pain as well as perceived pain
      after different orthodontic procedures are recorded on the VAS by patients and
      returned back to orthodontic office. The data are analyzed by SPSS 16.00 software
      by paired and independent t-test for the statistical significance. RESULTS: The
      result showed that there is significant difference between the anticipated pain
      before orthodontic treatment and the pain experienced following orthodontic
      treatment. It also showed that perception of pain between two sexes is
      significantly different. The comparison of anticipated pain among male and female
      does not show any significant difference, however the pain felt after separator
      placement as well as after orthodontic bonding is significantly different in two
      sexes. CONCLUSION: The level of anticipated pain before orthodontic treatment is
      higher than the real pain experienced after orthodontic procedures. So it is
      better to counsel and explain the patients about the orthodontic treatment and
      procedures.

PMID- 23132481
TI  - Accuracy of prediction of birth weight by fetal ultrasound.
AB  - BACKGROUND: Accurate determination of fetal weight prior to delivery can have a
      significant bearing on the management decision in labour, thereby markedly
      improving perinatal outcome. OBJECTIVE: To determine the accuracy of prediction
      of birth weight by fetal ultrasound. METHODS: This is the retrospective
      observational hospital based study done at Kathmandu medical college teaching
      hospital, Sinamangal, Kathmandu from January 2010 to February 2012. Total 150
      women with full term singleton pregnancy leading to live birth were included in
      this study. Prenatal fetal ultrasound database was reviewed for fetal weight
      estimation. Delivery records were reviewed for actual birth weight. Error in
      estimation was calculated. RESULTS: Our study showed that fetal ultrasound using
      Hadlock's formula has error in estimation of fetal weight by about 290 gm +/- 250
      gm. In 40% of the cases, there is an error of estimation by more than 10%
      compared to actual weight. CONCLUSION: Significant error was seen while
      estimating fetal weight by ultrasound. Depending only on the fetal ultrasound for
      the estimation of fetal weight can lead to unnecessary obstetrical intervention.
      It is thus necessary to correlate the ultrasound findings with clinical
      examination.

PMID- 23132482
TI  - Sirtuins: the future insight.
AB  - Sirtuins are evolutionary conserved NAD+ dependent acetyl-lysine deacetylases and
      ADP ribosyltransferases dual-function enzymes involved in the regulation of
      metabolism and lifespan. Sirtuins represent a promising new class of III NAD
      dependent histone deacetylases that regulate a number of physiological processes,
      originally identified in yeast. Sirtuins regulate various normal and abnormal
      cellular and metabolic processes, including tumorgenesis, neurodegeneration and
      processes associated with type 2 diabetes and obesity. Several age-related
      diseases such as Alzheimer's disease and longevity have also been linked to the
      functions of sirtuins. Because of these associations, the identification of small
      molecules sirtuin modulators has been of significant interest.

PMID- 23132483
TI  - Diarrhoeal diseases in developing countries: a situational analysis.
AB  - Recent data showed that there is no much reduction in diarrhoea related morbidity
      in developing countries. This is important in view of the Millennium
      Developmental Goal (MDG) to be achieved by 2015. This study reviewed and analyzed
      after gathering the recent literature information from Pubmed, internet and other
      sources. The authors discussed public health issues related to diarrhoeal
      diseases that include problem burden, determinants, intervention strategies,
      management, prevention and recent developments for control of diarrhoea among
      under-five children in developing countries. The study emphasizes the need for
      strengthening of comprehensive diarrhoeal disease prevention strategy at primary
      level including improvement of water quality, hygiene and sanitation, along with
      provision of oral rehydration solution and zinc supplements, and research in the
      field of vaccine and cost effective interventions.

PMID- 23132484
TI  - Chondrosarcoma of posterior nasal septum.
AB  - Chondrosarcoma is a rare non-epithelial tumor comprising of 10-20% of primary
      bone tumor. The nasal septum is a rare site for its occurrence. We present one
      such case of chondrosarcoma of the nasal septum who was treated with endoscopic
      removal followed by post operative radiotherapy and discuss the relevant clinical
      presentation, diagnosis and treatment and review the literature also.

PMID- 23132485
TI  - Spindle cell lipoma: a case report and review of literature.
AB  - Oral spindle cell lipoma is a rare lesion and until now only 26 cases have been
      reported in English literature. In this article we report a case of oral spindle
      cell lipoma presented to our institution in July 2011, as an asymptomatic
      solitary growth of the buccal mucosa in a 58 year old male patient. On
      histopathological examination the lesion exhibited an admixture of adipocytes and
      spindle cells with collagen fibres and numerous mast cells.

PMID- 23132486
TI  - Acute intermittent porphyria with SIADH and fluctuating dysautonomia.
AB  - Three cases of acute intermittent porphyria are reported. While in first case
      severe pain in abdomen with intermittent exacerbation was the only presentation,
      the second patient presented as accelerated hypertension and acute abdominal
      crises in whom the clinical course was characterized by development of deep coma
      due to inappropriate secretion of antidiuretic hormone before she made complete
      recovery. The third patient, initially manifested as acute encephalitic syndrome.
      After initial improvement, she developed features of acute intermittent porphyria
      i.e. acute abdomen, neuropsychiatric symptoms, and rapidly progressing acute
      motor neuropathy leading to respiratory and bulbar paralysis. In addition, she
      developed severe and fluctuating dysautonomia leading to cardiac arrest and fatal
      termination. The importance of early diagnosis, recognition of autonomic
      disturbances, prompt treatment and counseling for avoidance of precipitating
      factors is stressed.

PMID- 23132487
TI  - Anaesthetic management of a patient with dermatomyositis and valvular heart
      disease.
AB  - Dermatomyositis is an idiopathic inflammatory myopathy with involvement of
      muscle, skin and other organs. Valvular heart disease increases the risk of
      perioperative adverse cardiac events. Only a little information is available
      about the anaesthetic management of a patient with dermatomyositis and valvular
      heart disease. Here we considered combined spinal-epidural technique for total
      abdominal hysterectomy, minimizing the risk of delayed recovery from muscle
      relaxants, aspiration pneumonitis, arrhythmias and cardiac failure.

PMID- 23132488
TI  - Apocrine carcinoma developing in a naevus sebaceous of scalp.
AB  - Apocrine skin carcinoma is an aggressive cutaneous tumour. We report a case of
      apocrine carcinoma developing in a naevus sebaceous of scalp in a 45 years old
      male. Malignant transformation of Naevus sebaceous is a rare complication usually
      found in elderly patients. Most of these tumours are basal cell carcinoma or
      squamous cell carcinoma. Only few cases of apocrine carcinoma on naevus sebaceous
      have been previously reported. This report highlights the potential of naevus
      sebaceous for malignant transformation.

PMID- 23132489
TI  - Endoscopic excision of a fibroadenoma breast: trans axillary approach.
AB  - Benign breast lumps affect 10% of females in their lifetime. Surveillance,
      assurance, medications and surgical excision are options available to surgeons.
      Avoiding scars on the breast is an inherent feminine desire. Numerous minimal
      invasive approaches have evolved due to this concern. The time honoured
      circumareolar incisions camouflages the scar to a large extent, yet the incision
      still remains on the breast tissue and unfortunately the scar undergoes the same
      old sequelae as with any other scars both aesthetically or psychosocially. The
      close by anatomical space; axilla provides an easy access for endoscopic breast
      surgery. We utilized this area and applied our expertise to remove a fibroadenoma
      in a teenager which spared her breast from the scar. The technique was safe and
      effective. It conserved aesthetics and led to a better compliance.

PMID- 23132490
TI  - Combinatorial evaluation of laccase-mediator system in the oxidation of veratryl
      alcohol.
AB  - Laccases play an important role in the biological break down of lignin and have
      great potential in the deconstruction of lignocellulosic feedstocks. We examined
      16 laccases, both commercially prepared and crude extracts, for their ability to
      oxidize veratryl alcohol in the presence of various solvents and mediators.
      Screening revealed complete conversion of veratryl alcohol to veratraldehyde
      catalyzed by a crude preparation of the laccase from Trametes versicolor ATCC
      11235 and the mediator TEMPO in 20 % (v/v) tert-butanol.

PMID- 23132491
TI  - Toll-like receptor 2-dependent activity of native major outer membrane protein
      proteosomes of Chlamydia trachomatis.
AB  - Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen
      and the etiologic agent of blinding trachoma. Intracellular signaling pathways
      leading to host cell inflammation and innate immunity to Chlamydia include those
      mediated by Toll-like receptors (TLRs) and nucleotide binding oligomerization
      domain 1 (Nod1) protein. In epithelial cells, TLR-dependent signaling contributes
      to local immune responses via induction of inflammatory mediators. There is
      evidence that TLR3, TLR4, and, particularly, TLR2 are critical for Chlamydia
      mediated host cell activation and pathology. Despite the importance of TLR2,
      major chlamydial TLR2 antigens have not been identified so far. Numerous
      bacterial porins are known TLR2 agonists, i.e., porins from Neisseriae, Shigella,
      Salmonella, Haemophilus influenzae, and Fusobacterium nucleatum, which share
      structural and functional similarities with the chlamydial major outer membrane
      protein (MOMP), a strong antigen candidate for a potential vaccine against C.
      trachomatis. We describe the ability of purified, detergent-free MOMP to signal
      via TLR2 in vitro in TLR-overexpressing cells and TLR2-competent human
      reproductive tract epithelial cell lines. Using MOMP formed in pure protein
      micelles (proteosomes), we show the induction of TLR2-dependent interleukin-8 (IL
      8) and IL-6 secretion in vitro, the involvement of TLR1 as a TLR2 coreceptor, and
      the activation of both NF-kappaB and mitogen-activated protein (MAP) kinase
      intracellular pathways. Interestingly, MOMP proteosomes induce cytokine secretion
      in endocervical epithelial cells (End/E6E7) but not in urethral epithelial cells
      (THUECs). A detailed understanding of the TLR2-dependent molecular mechanisms
      that characterize the effect of MOMP proteosomes on host cells may provide new
      insights for its successful development as an immunotherapeutic target against
      Chlamydia.

PMID- 23132492
TI  - Enterococcus faecalis overcomes foreign body-mediated inflammation to establish
      urinary tract infections.
AB  - Urinary catheterization elicits major histological and immunological changes that
      render the bladder susceptible to microbial invasion, colonization, and
      dissemination. However, it is not understood how catheters induce these changes,
      how these changes act to promote infection, or whether they may have any
      protective benefit. In the present study, we examined how catheter-associated
      inflammation impacts infection by Enterococcus faecalis, a leading cause of
      catheter-associated urinary tract infection (CAUTI), a source of significant
      societal and clinical challenges. Using a recently optimized murine model of
      foreign body-associated UTI, we found that the implanted catheter itself was the
      primary inducer of inflammation. In the absence of the silicone tubing implant,
      E. faecalis induced only minimal inflammation and was rapidly cleared from the
      bladder. The catheter-induced inflammation was only minimally altered by
      subsequent enterococcal infection and was not suppressed by inhibitors of the
      neurogenic pathway and only partially by dexamethasone. Despite the robust
      inflammatory response induced by urinary implantation, E. faecalis produced
      biofilm and high bladder titers in these animals. Induction of inflammation in
      the absence of an implanted catheter failed to promote infection, suggesting that
      the presence of the catheter itself is essential for E. faecalis persistence in
      the bladder. Immunosuppression prior to urinary catheterization enhanced E.
      faecalis colonization, suggesting that implant-mediated inflammation contributes
      to the control of enterococcal infection. Thus, this study underscores the need
      for novel strategies against CAUTIs that seek to reduce the deleterious effects
      of implant-mediated inflammation on bladder homeostasis while maintaining an
      active immune response that effectively limits bacterial invaders.

PMID- 23132493
TI  - Major T cell response to a mycolyl glycolipid is mediated by CD1c molecules in
      rhesus macaques.
AB  - Human CD1b molecules contain a maze of hydrophobic pockets and a tunnel capable
      of accommodating the unusually long, branched acyl chain of mycolic acids, an
      essential fatty acid component of the cell wall of mycobacteria. It has been
      accepted that CD1b-bound mycolic acids constitute a scaffold for mycolate
      containing (glyco)lipids stimulating CD1b-restricted T cells. Remarkable homology
      in amino acid sequence is observed between human and monkey CD1b molecules, and
      indeed, monkey CD1b molecules are able to bind glucose monomycolate (GMM), a
      glucosylated species of mycolic acids, and present it to specific human T cells
      in vitro. Nevertheless, we found, unexpectedly, that Mycobacterium bovis bacillus
      Calmette-Guerin (BCG)-vaccinated monkeys exhibited GMM-specific T cell responses
      that were restricted by CD1c rather than CD1b molecules. GMM-specific, CD1c
      restricted T cells were detected in the circulation of all 4 rhesus macaque
      monkeys tested after but not before vaccination with BCG. The circulating GMM
      specific T cells were detected broadly in both CD4(+) and CD8(+) cell
      populations, and upon antigenic stimulation, a majority of the GMM-specific T
      cells produced both gamma interferon (IFN-gamma) and tumor necrosis factor alpha
      (TNF-alpha), two major host protective cytokines functioning against infection
      with mycobacteria. Furthermore, the GMM-specific T cells were able to extravasate
      and approach the site of infection where CD1c(+) cells accumulated. These
      observations indicate a previously inconceivable role for primate CD1c molecules
      in eliciting T cell responses to mycolate-containing antigens.

PMID- 23132494
TI  - Multifunctional role of human SPLUNC1 in Pseudomonas aeruginosa infection.
AB  - The human short PLUNC1 (SPLUNC1) protein has been identified as a component of
      the pulmonary antimicrobial response based on its structural similarity to the
      bactericidal/permeability-increasing (BPI) protein. Using a genetically modified
      mouse model, we recently verified the antimicrobial activity of SPLUNC1 against
      Pseudomonas aeruginosa in vivo. To further define the mechanism of epithelial
      SPLUNC1-mediated antibacterial action, we carried out studies to determine how
      SPLUNC1 protects the host from acute respiratory infections. P. aeruginosa
      treated with recombinant human SPLUNC1 protein showed decreased growth in vitro.
      This antibacterial activity was due to growth inhibition, as a consequence of a
      SPLUNC1-induced increase in bacterial cell permeability. Removal of SPLUNC1
      allowed the recovery of P. aeruginosa and suggested no permanent cell injury or
      direct killing of bacteria. Further investigation showed coating of bacterial
      cells by SPLUNC1. We suggest that this "bacterial cell coating" is necessary for
      the bacteriostatic function of SPLUNC1. Additionally, we demonstrated a novel
      role for SPLUNC1 as a chemoattractant that facilitated migration of macrophages
      and neutrophils. Taking the findings together, we propose synergistic roles for
      human SPLUNC1 as an antibacterial agent with bacteriostatic and chemotactic
      activities.

PMID- 23132495
TI  - Cryptococcus neoformans requires the ESCRT protein Vps23 for iron acquisition
      from heme, for capsule formation, and for virulence.
AB  - Iron availability is a key regulator of virulence factor elaboration in
      Cryptococcus neoformans, the causative agent of fungal meningoencephalitis in
      HIV/AIDS patients. In addition, iron is an essential nutrient for pathogen
      proliferation in mammalian hosts but little is known about the mechanisms of iron
      sensing and uptake in fungal pathogens that attack humans. In this study, we
      mutagenized C. neoformans by Agrobacterium-mediated T-DNA insertion and screened
      for mutants with reduced growth on heme as the sole iron source. Among 34
      mutants, we identified a subset with insertions in the gene for the ESCRT-I
      (endosomal sorting complex required for transport) protein Vps23 that resulted in
      a growth defect on heme, presumably due to a defect in uptake via endocytosis or
      misregulation of iron acquisition from heme. Remarkably, vps23 mutants were also
      defective in the elaboration of the cell-associated capsular polysaccharide that
      is a major virulence factor, while overexpression of Vps23 resulted in cells with
      a slightly enlarged capsule. These phenotypes were mirrored by a virulence defect
      in the vps23 mutant in a mouse model of cryptococcosis and by hypervirulence of
      the overexpression strain. Overall, these results reveal an important role for
      trafficking via ESCRT functions in both heme uptake and capsule formation, and
      they further reinforce the connection between iron and virulence factor
      deployment in C. neoformans.

PMID- 23132497
TI  - Surgical repair of bilateral levator ani muscles with ultrasound guidance: reply.

PMID- 23132496
TI  - Mycobacterium tuberculosis requires phosphate-responsive gene regulation to
      resist host immunity.
AB  - Mycobacterium tuberculosis persists in the tissues of mammalian hosts despite
      inducing a robust immune response dominated by the macrophage-activating cytokine
      gamma interferon (IFN-gamma). We identified the M. tuberculosis phosphate
      specific transport (Pst) system component PstA1 as a factor required to resist
      IFN-gamma-dependent immunity. A DeltapstA1 mutant was fully virulent in IFN
      gamma(-/-) mice but attenuated in wild-type (WT) mice and mice lacking specific
      IFN-gamma-inducible immune mechanisms: nitric oxide synthase (NOS2), phagosome
      associated p47 GTPase (Irgm1), or phagocyte oxidase (phox). These phenotypes
      suggest that DeltapstA1 bacteria are sensitized to an IFN-gamma-dependent immune
      mechanism(s) other than NOS2, Irgm1, or phox. In other species, the Pst system
      has a secondary role as a negative regulator of phosphate starvation-responsive
      gene expression through an interaction with a two-component signal transduction
      system. In M. tuberculosis, we found that DeltapstA1 bacteria exhibited
      dysregulated gene expression during growth in phosphate-rich medium that was
      mediated by the two-component sensor kinase/response regulator system SenX3
      RegX3. Remarkably, deletion of the regX3 gene suppressed the replication and
      virulence defects of DeltapstA1 bacteria in NOS2(-/-) mice, suggesting that M.
      tuberculosis requires the Pst system to negatively regulate activity of RegX3 in
      response to available phosphate in vivo. We therefore speculate that inorganic
      phosphate is readily available during replication in the lung and is an important
      signal controlling M. tuberculosis gene expression via the Pst-SenX3-RegX3 signal
      transduction system. Inability to sense this environmental signal, due to Pst
      deficiency, results in dysregulation of gene expression and sensitization of the
      bacteria to the host immune response.

PMID- 23132498
TI  - Surgical repair of bilateral levator ani muscles with ultrasound guidance:
      comment.

PMID- 23132499
TI  - Convergent stereoselective synthesis of multiple sulfated
      GlcNalpha(1,4)GlcAbeta(1,4) dodecasaccharides.
AB  - In this paper, we describe an effective method for the elongation of a
      GlcNalpha(1,4)GlcAbeta(1,4) sequence using a GlcNTrocalpha(1,4)GlcA disaccharide
      unit and the synthesis of the N- and/or O-sulfated GlcNalpha(1,4)GlcAbeta(1,4)
      oligosaccharides. N-Troc protection of GlcNalpha(1,4)GlcA units was effective for
      the synthesis of the GlcNalpha(1,4)GlcAbeta(1,4) oligosaccharides in comparison
      with the azido substituent. The GlcNalpha(1,4)GlcAbeta(1,4) dodecasaccharide was
      successfully prepared by the direct beta-selective glycosidation of glucuronate
      in the GlcNalpha(1,4)GlcAbeta(1,4)GlcNalpha(1,4)GlcAbeta(1,4) tetrasaccharide. In
      addition, the synthesis of the N- and/or O-sulfated GlcNalpha(1,4)GlcAbeta(1,4)
      oligosaccharides was accomplished by fluorous-assisted deprotection and
      sulfation. The fluorous-assisted synthetic technology applied to the highly polar
      sulfated oligosaccharide permits it to be more easily separated from the highly
      polar reagents, such as SO(3).NEt(3).

PMID- 23132500
TI  - Translational oncology toward benefiting cancer patients: the Sun Yat-sen
      University Cancer Center experience.

PMID- 23132501
TI  - Cationised gelatin and hyaluronic acid coating enhances polyethylene
      terephthalate artificial ligament graft osseointegration in porcine bone tunnels.
AB  - PURPOSE: The aim of this study was to investigate whether cationised gelatin and
      hyaluronic acid (CH) coating could induce polyethylene terephthalate (PET)
      artificial ligament graft osseointegration in the bone tunnel. METHODS: Surface
      modification of PET artificial ligament graft was performed by layer-by-layer
      (LBL) self-assembly CH coating. Six pigs underwent anterior cruciate ligament
      (ACL) reconstruction on the right knees, with three pigs receiving the CH-coated
      PET grafts and the other three pigs non-CH-coated PET grafts as controls. They
      were sacrificed at three months after surgery and the graft-bone complexes were
      acquired for computed tomography (CT) scan and histological examination. RESULTS:
      CT scans showed a significant difference at the distal femoral site (p = 0.031)
      or at the distal tibial site (p = 0.0078), but no significant difference in the
      bone tunnel areas' enlargement at other sites (p > 0.05) between the CH group and
      the control group. Histologically, application of CH coating induced new bone
      formation between graft and bone at three months compared with the controls at
      the distal site. The interface width of the CH group was significantly lower than
      that of the control group at the distal femoral site (p = 0.0327) and at the
      distal tibial site (p = 0.0047). CONCLUSIONS: The study has shown that CH coating
      on the PET artificial ligament surface has a positive biological effect in the
      induction of artificial ligament osseointegration within the bone tunnel at the
      distal site of the bone tunnel.

PMID- 23132502
TI  - One-stage total knee arthroplasty for patients with osteoarthritis of the knee
      and extra-articular deformity.
AB  - PURPOSE: The purpose of this paper is to review our experience and study the
      feasibility and clinical results of one-stage total knee arthroplasty (TKA) for
      patients with osteoarthritis of the knee with extra-articular deformity. METHODS:
      Nine patients with osteoarthritis of the knee associated with extra-articular
      deformity underwent one-stage TKA from June 2006 to April 2010. There were two
      men and seven women, with an average age of 51 years (range 34-69 years); four of
      them had tibial deformities and five had femoral deformities. Eight of the cases
      resulted from malunion after fracture healing and one from femoral recurvatum.
      Six of the cases had uniplanar and three had biplanar deformities. The average
      angles of the femoral deformities were 13.3 degrees  in the coronal plane (8-22)
      and 11.3 degrees  in the sagittal plane (6-15); one femur had 10 degrees 
      external rotational deformity. Tibial deformity of 16 degrees  in the coronal
      plane (11-22) was noted, and one had sagittal plane deformity of 21 degrees .
      RESULTS: All patients were followed for an average of 29 months. The average
      Hospital for Special Surgery (HSS) knee score improved from 18.7 points pre
      operatively to 89.8 points at the time of last follow-up; the range of knee
      motion improved from 46.7 degrees  preoperatively to 100.6 degrees 
      postoperatively. The average angle of mechanical axis deviation was restored from
      11.8 degrees  preoperatively to 1 degrees  postoperatively. One of the patients
      had unsatisfactory clinical results due to delayed union at the osteotomy site.
      No complications such as infection, deep vein thrombosis, ligament instability,
      low level or subluxed/dislocated patella or component loosening were observed.
      One-stage TKA with intra-articular correction of the extra-articular deformity
      was performed in seven patients, included proper planning, appropriate bone cuts
      to restore alignment and the necessary soft tissue releases to balance the knee
      in flexion and extension. Two patients underwent simultaneous extra-articular
      correctional osteotomy and TKA because the deformity was so large. Five knees
      that had good collateral ligamentous stability and balance received a posterior
      stabilised prosthesis; four knees that had ligamentous instability received a
      constrained condylar knee (CCK) prosthesis. CONCLUSIONS: One-stage TKA is a
      technically difficult but effective treatment for patients with osteoarthritis of
      the knee and extra-articular deformity. If feasible we recommend TKA with intra
      articular bone resection and soft tissue balancing.

PMID- 23132503
TI  - What is the risk of stress risers for interprosthetic fractures of the femur? A
      biomechanical analysis.
AB  - PURPOSE: Due to increasing life expectancy we see a rising number of joint
      replacements. Along with the proximal prosthesis in the femur, more and more
      people have a second implant on the distal ipsilateral side. This might be a
      retrograde nail or a locking plate to treat distal femur fractures or a
      constrained knee prosthesis in the case of severe arthrosis. All these constructs
      can lead to fractures between the implants. The goal of this study was to
      evaluate the risk of stress risers for interprosthetic fractures of the femur.
      METHODS: Thirty human cadaveric femurs were divided into five groups: (1) femurs
      with a prosthesis on the proximal side only, (2) hip prosthesis on the proximal
      end and a distal femur nail, (3) femurs with both a hip prosthesis and a
      constrained knee prosthesis, (4) femurs with a hip prosthesis on the proximal
      side and a 4.5-mm distal femur locking plate; the locking plate was 230 mm in
      length, with ten holes in the shaft, and (5) femurs with a proximal hip
      prosthesis and a 4.5-mm distal femur locking plate; the locking plate was 342 mm
      in length, with 16 holes in the shaft. RESULTS: Femurs with a hip prosthesis and
      knee prosthesis showed significantly higher required fracture force compared to
      femurs with a hip prosthesis and a distal retrograde nail. Femurs with a distal
      locking plate of either length showed a higher required fracture force than those
      with the retrograde nail. CONCLUSIONS: The highest risk for a fracture in the
      femur with an existing hip prosthesis comes with a retrograde nail. A distal
      locking plate for the treatment of supracondylar fractures leads to a higher
      required fracture force. The implantation of a constrained knee prosthesis that
      is not loosened on the ipsilateral side does not increase the risk for a
      fracture.

PMID- 23132505
TI  - D-peaks: a visual tool to display ChIP-seq peaks along the genome.
AB  - ChIP-sequencing is a method of choice to localize the positions of protein
      binding sites on DNA on a whole genomic scale. The deciphering of the sequencing
      data produced by this novel technique is challenging and it is achieved by their
      rigorous interpretation using dedicated tools and adapted visualization programs.
      Here, we present a bioinformatics tool (D-peaks) that adds several possibilities
      (including, user-friendliness, high-quality, relative position with respect to
      the genomic features) to the well-known visualization browsers or databases
      already existing. D-peaks is directly available through its web interface
      http://rsat.ulb.ac.be/dpeaks/ as well as a command line tool.

PMID- 23132506
TI  - RNA polymerase stalls in a post-translocated register and can hyper-translocate.
AB  - Exonuclease (Exo) III was used to probe translocation states of RNA polymerase
      (RNAP) ternary elongation complexes (TECs). Escherichia coli RNAP stalls
      primarily in a post-translocation register that makes relatively slow excursions
      to a hyper-translocated state or to a pre-translocated state. Tagetitoxin (TGT)
      strongly inhibits hyper-translocation and inhibits backtracking, so, as indicated
      by Exo III mapping, TGT appears to stabilize both the pre- and probably a
      partially post-translocation state of RNAP. Because the pre-translocated to post
      translocated transition is slow at many template positions, these studies appear
      inconsistent with a model in which RNAP makes frequent and rapid (i.e.,
      millisecond phase) oscillations between pre- and post-translocation states. Nine
      nucleotides (9-nt) and 10-nt TECs, and TECs with longer nascent RNAs, have
      distinct translocation properties consistent with a 9-10 nt RNA/DNA hybrid. RNAP
      mutant proteins in the bridge helix and trigger loop are identified that inhibit
      or stimulate forward and backward translocation.

PMID- 23132508
TI  - Randomized clinical trial of goal-directed fluid therapy within an enhanced
      recovery protocol for elective colectomy.
AB  - BACKGROUND: Goal-directed fluid therapy (GDFT) has been compared with liberal
      fluid administration in non-optimized perioperative settings. It is not known
      whether GDFT is of value within an enhanced recovery protocol incorporating fluid
      restriction. This study evaluated GDFT under these circumstances in patients
      undergoing elective colectomy. METHODS: Patients undergoing elective laparoscopic
      or open colectomy within an established enhanced recovery protocol (including
      fluid restriction) were randomized to GDFT or no GDFT. Bowel preparation was
      permitted for left colonic operations at the surgeon's discretion. Exclusion
      criteria included rectal tumours and stoma formation. The primary outcome was a
      patient-reported surgical recovery score (SRS). Secondary endpoints included
      clinical outcomes and physiological measures of recovery. RESULTS: Eighty-five
      patients were randomized, and there were 37 patients in each group for analysis.
      Nine patients in the GDFT and four in the fluid restriction group received oral
      bowel preparation for either anterior resection (12) or subtotal colectomy (1).
      Patients in the GDFT group received more colloid during surgery (mean 591 versus
      297 ml; P = 0.012) and had superior cardiac indices (mean corrected flow time 374
      versus 355 ms; P = 0.018). However, no differences were observed between the GDFT
      and fluid restriction groups with regard to surgical recovery (mean SRS after 7
      days 47 versus 46 respectively; P = 0.853), other secondary outcomes (mean
      aldosterone/renin ratio 9 versus 8; P = 0.898), total postoperative fluid (median
      3750 versus 2400 ml; P = 0.604), length of hospital stay (median 6 versus 5 days;
      P = 0.570) or number of patients with complications (26 versus 27; P = 1.000).
      CONCLUSION: GDFT did not provide clinical benefit in patients undergoing elective
      colectomy within a protocol incorporating fluid restriction. REGISTRATION NUMBER:
      NCT00911391 (http://www.clinicaltrials.gov).

PMID- 23132507
TI  - Protein metalation by metal-based drugs: reactions of cytotoxic gold compounds
      with cytochrome c and lysozyme.
AB  - Protein metalation processes are crucial for the mechanism of action of several
      anticancer metallodrugs and warrant deeper characterisation. We have explored the
      reactions of three cytotoxic gold(III) compounds-namely [(bipy(2Me))(2)Au(2)(MU
      O)(2)][PF(6)](2) (where bipy(2Me) is 6,6'-dimethyl-2,2'-bipyridine) (Auoxo6),
      [(phen(2Me))(2)Au(2)(MU-O)(2)][PF(6)](2) (where phen(2Me) is 2,9-dimethyl-1,10
      phenanthroline) (Au(2)phen) and [(bipy(dmb)-H)Au(OH)][PF(6)] [where bipy(dmb)-H
      is deprotonated 6-(1,1-dimethylbenzyl)-2,2'-bipyridine] (Aubipyc)-with two
      representative model proteins, i.e. horse heart cytochrome c and hen egg white
      lysozyme, through UV-visible absorption spectroscopy and electrospray ionisation
      mass spectrometry (ESI MS) to characterise the inherent protein metalation
      processes. Notably, Auoxo6 and Au(2)phen produced stable protein adducts where
      one or more "naked" gold(I) ions are protein-coordinated; very characteristic is
      the case of cytochrome c, which upon reaction with Auoxo6 or Au(2)phen
      preferentially forms "tetragold" adducts with four protein-bound gold(I) ions. In
      turn, Aubipyc afforded monometalated protein adducts where the structural core of
      the gold(III) centre and its +3 oxidation state are conserved. Auranofin yielded
      protein derivatives containing the intact auranofin molecule. Additional studies
      were performed to assess the role played by a reducing environment in protein
      metalation. Overall, the approach adopted provides detailed insight into the
      formation of metallodrug-protein derivatives and permits trends, peculiarities
      and mechanistic details of the underlying processes to be highlighted. In this
      respect, electrospray ionisation mass spectrometry is a very straightforward and
      informative research tool. The protein metalation processes investigated
      critically depend on the nature of both the metal compound and the interacting
      protein and also on the solution conditions used; thus, predicting with accuracy
      the nature and the amounts of the adducts formed for a given metallodrug-protein
      pair is currently extremely difficult.

PMID- 23132509
TI  - On the polymorphism of griseofulvin: identification of two additional polymorphs.
AB  - In this paper, we present an investigation of the polymorphism of griseofulvin.
      In addition to the only reported crystalline form (form I), two new polymorphic
      forms (II and III) have been identified and characterized by differential
      scanning calorimetry and powder X-ray diffraction. Reasons why these two
      polymorphs were isolated during the present study, but not detected during the
      numerous previous studies on this drug, are also discussed.

PMID- 23132510
TI  - Respiratory impact of analgesic strategies for shoulder surgery.
AB  - Shoulder surgery is associated with significant postoperative pain in many
      patients. The use of an interscalene nerve block offers good analgesia but is
      associated with a high incidence of an ipsilateral phrenic nerve block. Several
      strategies to avoid this adverse effect have been studied. Possible strategies
      are (1) using very low volumes of local anesthetics, (2) targeting the brachial
      plexus at a lower level in the neck, (3) applying a suprascapular nerve block,
      and (4) applying the combination of a suprascapular and an axillary nerve block.
      Using systemic analgesics is a less favorable strategy because this may result in
      less potent analgesia and may cause more adverse effects, including respiratory
      depression and nausea.

PMID- 23132511
TI  - Progression of macular atrophy after PDT combined with the COX-2 inhibitor
      Nabumetone in the treatment of neovascular ARMD.
AB  - AIM: To evaluate photodynamic therapy (PDT) combined with the preferential the
      cyclooxygenase-2 (COX-2) inhibitor, nabumetone in the treatment of the
      neovascular age-related macular degeneration (ARMD). METHODS: A prospective,
      double-blind, randomized study on 60 patients with subfoveal CNV secondary to
      ARMD without any previous treatment. Patients were divided into a nabumetone or
      placebo group. The main endpoints were the change of best-corrected visual acuity
      (BCVA), central macular thickness (CRT) and number of required PDT treatments.
      RESULTS: In the nabumetone group, 27 patients (90%) and 28 (93%) in the placebo
      group completed the follow-up of 12 months. In the nabumetone group, the mean CRT
      decreased from 332 MUm (SD 68 MUm) to 220 MUm (SD 46 MUm). In the placebo group,
      CRT decreased from 331 MUm (SD 72 MUm) to 254 MUm (SD 61 MUm). The mean BCVA was
      0.68 log MAR (SD 0.22 log MAR) in the nabumetone group and 0.62 log MAR (SD 0.23
      log MAR) in the placebo group at baseline. This stabilised in the placebo group
      to 0.66 log MAR (SD 0.33) but deteriorated in the nabumetone group to 0.86 log
      MAR (SD 0.41 log MAR). There was a significant reduction in the number of
      required PDTs in the nabumetone group, but significant progression of the RPE
      atrophy area. CONCLUSION: Combined PDT with oral intake of the COX-2 inhibitor,
      nabumetone reduced the number of required PDT retreatments, but worsening BCVA
      caused by macular atrophy progression. Therefore the combination of the PDT with
      the nabumetone is not recommended.

PMID- 23132512
TI  - Cytogenetics and molecular cytogenetics in diffuse large B-cell lymphoma (DLBCL).
AB  - BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) accounts for up to 40% of all
      non-Hodgkin's lymphomas diagnosed in the western hemisphere. Determination of the
      gene expression profile has confirmed the physiological heterogeneity of the
      disease and defined three molecular prognostic subgroups - germinal center B-cell
      like (GCB), activated B-cell-like (ABC) and primary mediastinal B-cell lymphoma
      (PMBL) - with different gene expression and prognosis. METHODS AND RESULTS: This
      review covers current knowledge on the most frequent recurrent cytogenetic and
      molecular cytogenetic aberrations in molecular DLBCL subgroups. CONCLUSIONS:
      Cytogenetic and molecular cytogenetic techniques used to determine nonrandom
      chromosomal aberrations in patients with DLBCL have revealed the incidence of
      frequent cytogenetic aberrations in the subgroups reported, suggesting their
      potential use for more accurate prognostic stratification of DLBCL, contributing
      to personalized selection of the most effective therapy.

PMID- 23132513
TI  - Vancomycin pharmacokinetics during high-volume continuous venovenous
      hemofiltration in critically ill septic patients.
AB  - AIMS: To assess the influence of continuous venovenous hemofiltration (CVVH) at a
      filtration rate of 45 mL/kg/h on vancomycin pharmacokinetics in critically ill
      septic patients with acute kidney injury (AKI). METHODS: Seventeen adult septic
      patients with acute kidney injury treated with CVVH and vancomycin were included.
      All patients received first dose of 1.0 g intravenously followed by 1.0 g/12 h if
      not adjusted. In sixteen patients vancomycin was introduced on the day of the
      start of CRRT therapy. Blood samples and ultrafiltrates were obtained before and
      0.5, 1, 6 and 12 h after vancomycin administration. RESULTS: On the first day,
      the median total vancomycin clearance (Cltot) was 0.89 mL/min/kg (range 0.31 -
      2.16). CRRT clearance accounted for around 50-60% of the total clearance of
      vancomycin found in a population with normal renal function (0.97 mL/min/kg).
      Vancomycin serum concentrations after the first dose were below the required
      target of 10 mg/L as early as 6 h in 10 patients, AUC0-24/MIC >= 400 ratio was
      achieved in 10 patients on the first day. CONCLUSIONS: CVVH at a filtration rate
      of 45 mL/kg/h leads to high and rapid extracorporeal removal of vancomycin in
      critically ill patients. Due to the rapid change in patient clinical status it
      was impossible to predict a fixed dosage regimen. We recommend blood sampling as
      early as 6 h after first vancomycin dose with maintenance dose based on
      vancomycin serum level monitoring.

PMID- 23132514
TI  - The epidemiology of thyroid cancer in the Czech Republic in comparison with other
      countries.
AB  - BACKGROUND: Thyroid cancer includes a broad spectrum of tumours with different
      prognoses. The global incidence has been increasing in recent years. Variables
      affecting its etiology are dietary, especially iodine intake and to a lesser
      extent selenium, environmental, like - ionizing radiation and, increased TSH
      level. These factors interplay with epigenetic and genetic changes within the
      cell. This review article presents thyroid cancer epidemiology, describes its
      main characteristics and the influence of environmental and lifestyle risk
      factors in the Czech Republic in comparison with other countries. METHODS AND
      RESULTS: An epidemiological study of Czech patients with malignant thyroid
      carcinoma was made on the basis of the National Oncologic Registry (NOR) and
      Czech Statistical Office data summarized on the web portal SVOD. The data were
      compared with international data from the project GLOBOCAN 2008 Cancer Incidence
      and Mortality Worldwide. Apart from risk factors, prognostic factors with effect
      on patient survival were also analyzed. The survey showed that the incidence of
      thyroid cancer has been steadily growing in the Czech Republic. Since the
      beginning of the 1980s, it has increased 4 fold. It has a higher incidence than
      most other European countries but it is ranked with countries with an average and
      decreasing mortality. Obviously, the improved detection methods do not explain
      the growing incidence. The highest incidence is found for papillary carcinoma
      (PTC), now over 80% of cases. For follicular and medullar cancers, the incidence
      has not increased and for anaplastic carcinoma there is a slight decrease. Women
      over 40 years of age constitute the highest risk group. CONCLUSIONS: There are a
      number of reasons for these trends, such as improved diagnostic techniques using
      ultrasound and FNAB and more radical surgery. There are also
      dietary/environmental factors (iodine deficiency and to a lesser extent
      selenium), nitrates, polychlorinated biphenyls, increased ionizing radiation, and
      prolonged increase in TSH. The prognosis of patients with DTC depends on the age
      at the time of diagnosis. A favorable prognosis also depends on timely detection.

PMID- 23132515
TI  - Where are the young men in HIV prevention efforts? Comments on HIV prevention
      programs and research from young men who sex with men in Los Angeles county.
AB  - Despite increasing rates of HIV infection among young men who have sex with men
      (YMSM), only a minority participate in formal HIV prevention efforts. Semi
      structured mixed-methods interviews were conducted with a diverse sample of YMSM
      (N = 100, M(age) = 25.0 years) in Los Angeles, California, to identify
      facilitators and barriers to participation in HIV prevention programs. Summative
      content analyses were used to evaluate transcribed field notes from these
      interviews. Results showed that 28.0 % of all participants had previously
      attended an HIV prevention program, and that 21.3 % of those who were also asked
      if they had ever participated in any research pertaining to HIV prevention had
      done so. A significantly higher percentage of those who had participated in HIV
      prevention programs had been tested for HIV in the past 6 months compared to
      those who had not (p < .05). The most frequently mentioned barriers to
      participation in such a program were being too busy to attend (12.0 %), not
      perceiving themselves to be at risk for HIV infection (14.0 %), and believing
      that they already knew everything they needed to know about HIV transmission
      (23.0 %). YMSM suggested that future interventions should use technology (e.g.,
      the Internet, mobile devices), engage their social networks, and highlight HIV
      prevention as a means for community connection. Collectively, these results
      provide some explanations for why YMSM account for a minority of HIV prevention
      program participants and offer possible directions for future HIV prevention
      efforts that target YMSM.

PMID- 23132516
TI  - Health-as-a-value, spirituality, and cigarette and alcohol use among Russian high
      school students.
AB  - National estimates suggest that the prevalence of tobacco and alcohol use is
      higher among adolescents in Russia than among adolescents in the United States
      and other European countries. However, research on the psychosocial correlates
      of, as well as protective factors for, tobacco and alcohol use among Russian
      adolescents has been relatively limited. Research conducted primarily in the
      United States has shown that spirituality and health-as-a-value are plausible
      predictors of adolescent substance use. However, these constructs have not been
      extensively studied in regions outside the United States. In this study, we
      tested whether spirituality and heath-as-a-value had protective effects on past
      month cigarette and alcohol use behaviors and next-year cigarette and alcohol use
      intentions among Russian high school students (N = 354, mean age = 15.7 years),
      after controlling for known predictors of adolescent substance use such as age,
      gender, socioeconomic status, peer substance use, and sensation seeking. We found
      a significant inverse relationship between health-as-a-value and recent cigarette
      and alcohol use as well as future cigarette use intentions. However, we did not
      find a significant relationship between spirituality and any substance use
      variables. Implications of these findings for school-based substance use
      prevention are discussed.

PMID- 23132517
TI  - Comprehensive framework for accurate diffusion MRI parameter estimation.
AB  - During the last decade, many approaches have been proposed for improving the
      estimation of diffusion measures. These techniques have already shown an increase
      in accuracy based on theoretical considerations, such as incorporating prior
      knowledge of the data distribution. The increased accuracy of diffusion metric
      estimators is typically observed in well-defined simulations, where the
      assumptions regarding properties of the data distribution are known to be valid.
      In practice, however, correcting for subject motion and geometric eddy current
      deformations alters the data distribution tremendously such that it can no longer
      be expressed in a closed form. The image processing steps that precede the model
      fitting will render several assumptions on the data distribution invalid,
      potentially nullifying the benefit of applying more advanced diffusion
      estimators. In this work, we present a generic diffusion model fitting framework
      that considers some statistics of diffusion MRI data. A central role in the
      framework is played by the conditional least squares estimator. We demonstrate
      that the accuracy of that particular estimator can generally be preserved,
      regardless the applied preprocessing steps, if the noise parameter is known a
      priori. To fulfill that condition, we also propose an approach for the estimation
      of spatially varying noise levels.

PMID- 23132518
TI  - Spotlight on 'xeroderma pigmentosum'.
AB  - Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder of DNA repair
      characterised by photosensitivity, progressive pigmentary change, and an
      increased incidence of ultraviolet (UV)-induced skin and mucous membrane cancers.
      Approximately 25% of XP patients also have progressive neurological degeneration.
      There are eight XP complementation groups (XP-A through to XP-G, and XP variant
      (XP-V)), corresponding to the affected DNA repair gene. Seven of these genes, XPA
      to XPG, are involved in nucleotide excision repair, removing UV-induced damage
      from DNA. The eighth gene, XPV (or POLH), encodes for DNA polymerase eta, which
      is required for the replication of DNA containing unrepaired UV-induced damage.
      There is wide variability in clinical features both between and within XP
      complementation groups. The diagnosis is made clinically and confirmed by
      cellular tests for defective DNA repair. This is followed by identification of
      the defective gene (complementation analysis) and causative mutation(s). Although
      there is no cure, sun avoidance and regular follow-up to assess and treat any
      skin cancers increase life expectancy. The neurological abnormalities are
      progressive and result in a shortened lifespan. The study of patients with XP has
      highlighted the importance of nucleotide excision repair in the aetiology of skin
      cancers and neurological degeneration, and has solidified the link between UV
      exposure, DNA damage, somatic mutations and skin cancer.

PMID- 23132519
TI  - List-method directed forgetting can be selective: evidence from the 3-list and
      the 2-list tasks.
AB  - When people are cued to forget previously studied irrelevant information and
      study new information instead, such cuing typically leads to forgetting of the
      precue information. But what do people forget if, before the forget cue is
      provided, both irrelevant and relevant information have been encoded? Using
      relatively short item lists, we examined in a series of three experiments whether
      participants are able to selectively forget the irrelevant precue information,
      when relevant and irrelevant precue items were presented subsequently in two
      separate lists (3-list task) and when the two types of items were presented
      alternatingly within a single list (2-list task). Selective forgetting of the
      irrelevant precue items arose in the 3-list task, independent of modality of item
      presentation and level of discriminability of the precue lists, and it arose in
      the 2-list task. The findings suggest that, at least with relatively short precue
      lists, participants may well be able to selectively forget irrelevant precue
      information when cued to do so. Implications of the results for theoretical
      accounts of list-method directed forgetting are discussed.

PMID- 23132520
TI  - Sperm pretreatment with dithiothreitol increases male pronucleus formation rates
      after intracytoplasmic sperm injection (ICSI) in swamp buffalo oocytes.
AB  - Failure of male pronucleus formation has hampered the success of intracytoplasmic
      sperm injection (ICSI) in swamp buffalo. The aim of the present study was to
      improve male pronucleus formation by pretreating sperm with various chemicals
      before ICSI. In Experiments1 and 2, sperm were treated according to one of the
      following protocols: (1) 0.1% Triton-X 100 (TX) for 1 min, (2) 10 MUM calcium
      ionophore (CaI) for 20 min, (3) freezing and thawing (FT) without any
      cryoprotectant, or (4) no treatment (control). These sperm treatment groups then
      either did or did not receive additional sperm treatment with 5 mM dithiothreitol
      (DTT) for 20 min. Acrosomal integrity (Experiment 1) and DNA fragmentation
      (Experiment 2) were evaluated in the sperm before ICSI. In Experiment 3, oocytes
      matured in vitro were subjected to ICSI using pretreated sperm as described above
      and then were cultured either with or without activation. The TX- and CaI-treated
      sperm caused an increase in the number of acrosome-loss sperm, whereas the FT
      treatment and control increased the proportion of acrosome-reacted sperm
      (P<0.05). The DNA fragmentation did not differ among treatments (P>0.05). At 18 h
      post-ICSI, pronucleus (PN) formation was found only in activated oocytes. The
      majority of the activated ICSI oocytes contained intact sperm heads. Normal
      fertilization was observed in the CaI and FT treatment groups and control group
      when sperm were treated with DTT before ICSI. In conclusion, DTT treatment of
      sperm with reacted acrosomes before ICSI together with activation of the ICSI
      oocytes is important for successful male pronucleus formation.

PMID- 23132521
TI  - Induced somatic sector analysis of cellulose synthase (CesA) promoter regions in
      woody stem tissues.
AB  - The increasing focus on plantation forestry as a renewable source of cellulosic
      biomass has emphasized the need for tools to study the unique biology of woody
      genera such as Eucalyptus, Populus and Pinus. The domestication of these woody
      crops is hampered by long generation times, and breeders are now looking to
      molecular approaches such as marker-assisted breeding and genetic modification to
      accelerate tree improvement. Much of what is known about genes involved in the
      growth and development of plants has come from studies of herbaceous models such
      as Arabidopsis and rice. However, transferring this information to woody plants
      often proves difficult, especially for genes expressed in woody stems. Here we
      report the use of induced somatic sector analysis (ISSA) for characterization of
      promoter expression patterns directly in the stems of Populus and Eucalyptus
      trees. As a case study, we used previously characterized primary and secondary
      cell wall-related cellulose synthase (CesA) promoters cloned from Eucalyptus
      grandis. We show that ISSA can be used to elucidate the phloem and xylem
      expression patterns of the CesA genes in Eucalyptus and Populus stems and also
      show that the staining patterns differ in Eucalyptus and Populus stems. These
      findings show that ISSA is an efficient approach to investigate promoter function
      in the developmental context of woody plant tissues and raise questions about the
      suitability of heterologous promoters for genetic manipulation in plant species.

PMID- 23132522
TI  - Cloning and characterization of a tuberous root-specific promoter from cassava
      (Manihot esculenta Crantz).
AB  - In order to obtain a tuberous root-specific promoter to be used in the
      transformation of cassava, a 1,728 bp sequence containing the cassava granule
      bound starch synthase (GBSSI) promoter was isolated. The sequence proved to
      contain light- and sugar-responsive cis elements. Part of this sequence (1,167
      bp) was cloned into binary vectors to drive expression of the firefly luciferase
      gene. Cassava cultivar Adira 4 was transformed with this construct or a control
      construct in which the luciferase gene was cloned behind the 35S promoter.
      Luciferase activity was measured in leaves, stems, roots and tuberous roots. As
      expected, the 35S promoter induced luciferase activity in all organs at similar
      levels, whereas the GBSSI promoter showed very low expression in leaves, stems
      and roots, but very high expression in tuberous roots. These results show that
      the cassava GBSSI promoter is an excellent candidate to achieve tuberous root
      specific expression in cassava.

PMID- 23132523
TI  - Direct synthesis of ordered mesoporous carbons.
AB  - Ordered mesoporous carbon materials have recently aroused great research interest
      because of their widespread applications in many areas such as adsorbents,
      catalysts and supports, gas storage hosts, and electrode materials. The direct
      synthesis strategy from organic-organic self-assembly involving the combination
      of polymerizable precursors and block copolymer templates is expected to be more
      flexible in preparing mesoporous carbons, compared with the traditional
      nanocasting strategy of complicated and high-cost procedures using mesoporous
      silica materials as the hard template. In this review, we present the
      fundamentals and recent advances related to the field of ordered mesoporous
      carbon materials from the direct synthesis strategy of block copolymer soft
      templating, with a focus on their controllable preparation, modification and
      potential applications. Under the guidance of their formation mechanism, the
      preparation of ordered mesoporous carbons are discussed in detail by consulting
      different experimental conditions, including synthetic pathways, precursors,
      catalysts and templates. Both the mesopore size and morphology control are
      introduced. The potential applications of pure mesoporous carbons, nonmetallic-
      and metallic-modified mesoporous carbons, and some interpenetrating carbon-based
      composites are demonstrated. Furthermore, remarks on the challenges and
      perspectives of research directions are proposed for further development of the
      ordered mesoporous carbons (232 references).

PMID- 23132524
TI  - Fundamental principles of data assimilation underlying the Verdandi library:
      applications to biophysical model personalization within euHeart.
AB  - We present the fundamental principles of data assimilation underlying the
      Verdandi library, and how they are articulated with the modular architecture of
      the library. This translates--in particular--into the definition of standardized
      interfaces through which the data assimilation library interoperates with the
      model simulation software and the so-called observation manager. We also survey
      various examples of data assimilation applied to the personalization of
      biophysical models, in particular, for cardiac modeling applications within the
      euHeart European project. This illustrates the power of data assimilation
      concepts in such novel applications, with tremendous potential in clinical
      diagnosis assistance.

PMID- 23132525
TI  - A classification scheme for ventricular arrhythmias using wavelets analysis.
AB  - Identification and classification of ventricular arrhythmias such as rhythmic
      ventricular tachycardia (VT) and disorganized ventricular fibrillation (VF) are
      vital tasks in guiding implantable devices to deliver appropriate therapy in
      preventing sudden cardiac deaths. Recent studies have shown VF can exhibit strong
      regional organizations, which makes the overlap zone between the fast paced
      rhythmic VT and VF even more ambiguous. Considering that implantable cardioverter
      defibrillator (ICD) are primarily rate dependent detectors of arrhythmias and
      that there may be patients who suffer from arrhythmias that fall in the overlap
      zone, it is essential to identify the degree of affinity of the arrhythmia toward
      VT or organized/disorganized VF. The method proposed in this work better
      categorizes the overlap zone using Wavelet analysis of surface ECGs. Sixty-three
      surface ECG signal segments from the MIT-BIH database were used to classify
      between VT, organized VF (OVF), and disorganized VF (DVF). A two-level binary
      classifier was used to first extract VT with an overall accuracy of 93.7% and
      then the separation between OVF and DVF with an accuracy of 80.0%. The proposed
      approach could assist clinicians to provide optimal therapeutic solutions for
      patients in the overlap zone of VT and VF.

PMID- 23132526
TI  - Classification of surface electromyographic signals by means of multifractal
      singularity spectrum.
AB  - In order to effectively control a prosthetic system, considerable attempts have
      been made in recent years to improve the classification accuracy of surface
      electromyographic (SEMG) signals. However, the extraction of effective features
      is still a primary challenge for the classification of SEMG signals. This study
      tried to solve the problem by applying the multifractal analysis. It was found
      that the SEMG signals were characterized by multifractality during forearm
      movements and different types of forearm movements were related to different
      multifractal singularity spectra. To quantitatively evaluate the multifractal
      singularity spectra of the SEMG signals, the areas of the singularity spectrum
      curves were calculated by integrating the spectrum curves with respect to the
      singularity strengths. Our results showed that there were several separate
      clusters resulting from singularity spectrum areas of different forearm movements
      when two channels of SEMG signals were used in this experimental research, which
      demonstrated that the multifractal analysis approach was suitable for identifying
      different types of forearm movements. By comparing with other feature extraction
      techniques, the multifractal singularity spectrum approach provided higher
      classification accuracy in terms of the classification of SEMG signals.

PMID- 23132527
TI  - 1H, 13C and 15N resonance assignments of the N-terminal domain of Vta1-Vps60
      peptide complex.
AB  - Vta1 and Vps60 are two ESCRT associated proteins, their direct interaction
      enhances Vps4 ATPase activity. The N-terminal domain of Vta1 (residues 1-167aa,
      named as Vta1NTD) contains two tandem MIT domains, which specifically recognize
      Vps60 and Did2 but not other ESCRT-III subunits. The fragment Vps60 (128-186aa)
      was reported to display full activity of Vps60, which stimulates Vps4 ATPase in a
      Vta1-dependent manner. To study the structural basis for the interaction between
      Vta1 and Vps60, as a first step, here, we report the resonance assignments of the
      sequential backbone atoms and the side chains of the residues in the two
      components of Vta1NTD/Vps60(128-186) complex at pH 7.0 and 20  degrees C (BMRB
      No. 18521).

PMID- 23132528
TI  - Aging effects on detection of spectral changes induced by a break in sound
      correlation.
AB  - OBJECTIVES: Previous studies have shown that both younger adults and older adults
      with clinically normal hearing are able to detect a break in correlation (BIC)
      between interaurally correlated sounds presented over headphones. This ability to
      detect a BIC improved when the correlated sounds were presented over left and
      right loudspeakers rather than over left and right headphones, suggesting that
      additional spectral cues provided by comb filtering (caused by interference
      between the two channels) facilitate detection of the BIC. However, older adults
      receive significantly less benefit than younger adults from a switch to
      loudspeaker presentation. It is hypothesized that this is a result of an age
      related reduction in the sensitivity to the monaural spectral cues provided by
      comb filtering. DESIGN: Two experiments were conducted in this study. Correlated
      white noises with a BIC in the temporal middle were presented from two spatially
      separated loudspeakers (positioned at +/-45-degree azimuth) and recorded at the
      right ear of a Knowles Electronic Manikin for Acoustic Research (KEMAR). In
      Experiment 1, the waveforms recorded at the KEMAR's right ear were presented to
      the participant's right ear over a headphone in 14 younger adults and 24 older
      adults with clinically normal hearing. In Experiment 2, 8 of the 14 younger
      participants participated. Under the monaurally cueing condition, the waveforms
      recorded at the KEMAR's right ear were presented to the participant's right ear
      as Experiment 1. Under the binaurally cueing condition, waveforms delivered from
      the left loudspeaker and those from the right loudspeaker were recorded at the
      KEMAR's left and right ear, respectively, thereby eliminating the spectral ripple
      cue, and were presented to the participant's left and right ears, respectively.
      For each of the two experiments, the break duration threshold for detecting the
      BIC was examined when the interloudspeaker interval (delay) (ILI) was 0, 1, 2, or
      4 msec (left loudspeaker leading). RESULTS: In Experiment 1, both younger
      participants and older participants detected the BIC in the waveforms recorded by
      the right ear of KEMAR, but older participants had higher detection thresholds
      than younger participants when the ILI was 0, 2, or 4 msec without an effect of
      SPL shift between 59 and 71 dB. In Experiment 2, each of the eight younger
      participants was able to detect the occurrence of the BIC in either the
      monaurally cueing or binaural-cueing condition. In addition, the detection
      threshold under the monaurally cueing condition was substantially the same as
      that under the binaurally cueing condition at each of the four ILIs. CONCLUSIONS:
      Younger adults and older adults with clinically normal hearing are able to detect
      the monaural spectral changes arising from comb filtering when a sudden drop in
      intersound correlation is introduced. However, younger adults are more sensitive
      than older adults are, at detecting the BIC. The findings suggest that older
      adults are less able than younger adults to detect a periodic ripple in the sound
      spectrum. This age-related ability reduction may contribute to older adults'
      difficulties in hearing under noisy, reverberant conditions.

PMID- 23132529
TI  - Characterization of long-circulating cationic nanoparticle formulations
      consisting of a two-stage PEGylation step for the delivery of siRNA in a breast
      cancer tumor model.
AB  - Polyethylene glycol (PEG) has been used widely in liposomal formulations as a
      strategy to inhibit opsonization by plasma proteins and to prolong liposome
      plasma circulation time. PEG can be incorporated onto the surface of liposomes
      either during the spontaneous self-assembling process or inserted after vesicle
      formation. The advantages of employing the PEG postinsertion method include
      improved drug encapsulation efficiency and the ability to incorporate PEG
      conjugates for enhanced cell binding and uptake. In this study, we propose to
      evaluate a cationic lipid nanoparticle formulation containing two PEGylation
      steps: pre- and post-siRNA insertion. Our results indicate that formulations
      consisting of the extra PEG post-insertion step significantly increased siRNA
      circulation in the plasma by two-folds in comparison with the formulations
      consisting of only the single PEGylation step. Moreover, this formulation was
      able to efficiently carry siRNA to the tumor site, increase siRNA stability and
      significantly downregulate luciferase mRNA expression by >50% when compared with
      the controls in an intraperitoneal and subcutaneous breast cancer tumor model.
      Overall, our cationic lipid nanoparticle formulation displayed enhanced plasma
      circulation, reduced liver accumulation, enhanced tumor targeting, and effective
      gene knockdown--demonstrating excellent utility for the delivery of siRNA.

PMID- 23132530
TI  - Are single C60 fullerenes dielectric or metallic?
AB  - We present analytical solutions for the interaction energies between a static
      point charge and a metal- or a dielectric sphere. These solutions include
      polarization effects to infinite orders in the inverse of the distance between
      the point charge and the spheres. Further, we present Density Functional Theory
      (DFT) calculations of interaction energies for a point charge in ranges of fixed
      positions outside a neutral or a singly charged C(60) molecule. Based on these
      DFT results, we conclude that the metal sphere model describes the electronic
      response of the C(60) molecule much better than the dielectric sphere model.
      These findings are particularly important for calculations of energy barriers for
      charge transfer in reactions involving C(60) molecules. The metal- and dielectric
      models should further be useful for descriptions of, for example, the
      polarizabilities of and interactions with conducting and insulating spherical
      clusters or particles.

PMID- 23132531
TI  - Onyx embolization for the endovascular treatment of infectious and traumatic
      aneurysms involving the cranial and cerebral vasculature.
AB  - BACKGROUND: Onyx is a liquid non-adhesive viscous embolic agent ideal for slow
      targeted injections which is currently approved for the treatment of intracranial
      aneurysms and arteriovenous malformations. METHODS: We performed a single-center
      retrospective analysis of consecutive patients who underwent off-label use of
      Onyx as the single embolic agent for the treatment of traumatic or infectious
      pseudoaneurysms involving the cerebral or cranial vasculature. RESULTS: A total
      of nine pseudoaneurysms treated by Onyx embolization were identified. Six of the
      pseudoaneurysms were post-surgical, one of the pseudoaneurysms was traumatic and
      two were infectious in nature. The mean pseudoaneurysm size was 5.9 mm (range 2
      10 mm). Onyx-34 was used in all cases. Following treatment there was complete
      exclusion of all pseudoaneurysms including their inflow and outflow zones.
      CONCLUSIONS: Our experience demonstrates the efficacy and applicability of the
      use of Onyx in the treatment of complex traumatic and mycotic pseudoaneurysms
      involving the cerebral and cranial vascular tree.

PMID- 23132533
TI  - The clinical consequences of hemizygosity across 2 MB of 10q23 are restricted to
      Cowden syndrome.
AB  - Cowden syndrome is caused by germline mutations in PTEN and clinically
      characterized by hamartomas, macrocephaly, classic dermatologic stigmata, and an
      estimated 85 % lifetime risk of female breast cancer. A young woman with
      macrocephaly, tricholemmomas, AV malformations, and mammary papillomatosis was
      found to be hemizygous for PTEN in her germline DNA. Using MLPA, comparative
      genomic hybridization, and DNA sequencing, we identified a 2-Mb deletion in
      chromosome 10 spanning 344-kb centromeric and 1.7-Mb telomeric of PTEN. Her
      father who has a clinical history including macrocephaly, Hashimoto's
      thyroiditis, colonic polyposis, acral keratoses, and goiter was also found to
      have the same deletion. In benign breast tissue from the hemizygous female, PTEN
      protein expression was significantly reduced in luminal and stromal cells but
      present in the myoepithelium. Compared with a typical papilloma of the breast
      which had intense cytoplasmic PTEN staining, the majority of the patient's
      papilloma had significantly decreased PTEN expression while some cells had
      mislocalized perinuclear PTEN expression. In addition to PTEN, 22 other protein
      coding genes were deleted including two predicted haploinsufficient genes and
      five additional genes that have previously been associated with hereditary
      predispositions to certain diseases. However, because all significant clinical
      features of the proband and her father are common to patients with genetic
      alterations in PTEN, the other 22 hemizygous protein-coding genes appear to be
      haplosufficient.

PMID- 23132534
TI  - Dual association between polyphenol intake and breast cancer risk according to
      alcohol consumption level: a prospective cohort study.
AB  - Studies of the association between polyphenols dietary intake and breast cancer
      risk have been limited due to the lack of detailed food composition tables. In
      addition, none has examined this association according to alcohol intake, despite
      the facts that alcohol is an established risk factor for breast cancer and that
      the contribution of alcoholic beverages to polyphenol intake varies according to
      the level of alcohol consumption. Our objectives were (1) to estimate the
      associations between breast cancer risk and a wide range of dietary polyphenols
      using the recently published Phenol-Explorer database; and (2) to evaluate if/how
      alcohol intake modulates these relationships. 4,141 women from the SU.VI.MAX
      prospective cohort were followed from 1994 to 2007 (median followup: 12.6 years);
      152 developed a first incident invasive primary breast cancer. Dietary intakes
      were assessed by repeated 24-h records. The Phenol-Explorer database was used to
      estimate polyphenol intake. Multivariable Cox proportional hazards models were
      used to calculate hazard ratios (HRs) and 95 % confidence intervals (CIs) for
      quartiles of polyphenol intake. Analyses were stratified by median alcohol intake
      (< vs. >= 6.5 g/d). In non-to-low alcohol drinkers, intakes of some classes of
      polyphenols were associated with decreased breast cancer risk: hydroxybenzoic
      acids (HR(Q4vsQ1) = 0.38, 95 % CI: 0.17-0.86, P (trend) = 0.005), flavonoids
      (0.35, 0.17-0.75, P (trend) = 0.02), flavonols (0.36, 0.18-0.74, P (trend) =
      0.002), catechins (0.48, 0.22-1.05, P (trend) = 0.02), theaflavins (0.42, 0.19
      0.93, P (trend) = 0.02), and proanthocyanidins (0.39, 0.18-0.84, P (trend) =
      0.02). In contrast, in women with higher alcohol use, intakes of hydroxybenzoic
      acids (2.28, 1.16-4.49, P (trend) = 0.04), flavonoids (2.46, 1.23-4.92, P (trend)
      = 0.01), anthocyanins (2.94, 1.32-6.53, P (trend) = 0.01), catechins (2.28, 1.19
      4.36, P (trend) = 0.02), and proanthocyanidins (2.98, 1.40-6.33, P (trend) =
      0.006) were associated with increased breast cancer risk. In conclusion, this
      prospective study suggests that several classes of polyphenols could potentially
      contribute to breast cancer prevention among non-to-low alcohol drinkers, but
      some may increase breast cancer risk among women with higher alcohol intake.

PMID- 23132535
TI  - Systematic review of randomized controlled trials of clinical prediction rules
      for physical therapy in low back pain.
AB  - STUDY DESIGN: Systematic review. OBJECTIVE: To evaluate randomized controlled
      trials validating the effects of a clinical prediction rule for patients with non
      specific low back pain (LBP). The outcomes of interest were any back pain or pain
      related measures. SUMMARY OF BACKGROUND DATA: LBP is a common and costly
      condition. Interventions for back pain seem to have, at best, small to moderate
      mean beneficial effects. Identifying subgroups of patients who may respond better
      to certain treatments may help to improve clinical outcomes in back pain. The
      development of clinical prediction rules is an attempt to determine who will
      respond best to certain treatments. METHODS: We conducted electronic searches of
      MEDLINE (1980-2009), EMBASE (1980-2009), PsycINFO (1980-2009), Allied and
      Complementary Medicine (1980-2009), PubMed (1980-2009), ISI Web of Knowledge
      (1980-2009), and the Cochrane Library (1980-2009). The reference lists of
      relevant articles were searched for further references. RESULTS: We identified
      1821 potential citations; 3 articles were included. The results from the
      available data do not support the use of clinical prediction rules in the
      management of non-specific LBP. CONCLUSION: There is a lack of good quality
      randomized controlled trials validating the effects of a clinical prediction rule
      for LBP. Furthermore, there is no agreement on appropriate methodology for the
      validation and impact analysis. The evidence for, and development of, the
      existing prediction rules is generally weak.

PMID- 23132536
TI  - Diagnosis and treatment of Fusobacterium nucleatum discitis and vertebral
      osteomyelitis: case report and review of the literature.
AB  - STUDY DESIGN: Case report. OBJECTIVE: We present a case of vertebral
      osteomyelitis and discitis caused by Fusobacterium nucleatum in a 42-year-old
      female. SUMMARY OF BACKGROUND DATA: Infection of the vertebral bodies or disc
      space with this organism is rare. A review of the English literature disclosed 13
      cases of vertebral osteomyelitis caused by Fusobacterium spp. Because of the
      negative impact of this condition on the affected patients' activities of daily
      living, it is important to understand the clinical character and effective
      management of the disease to improve quality of life. Fusobacterium is an
      anaerobic and gram-negative microbe that is part of the normal flora of the
      mouth, gastrointestinal tract, and female genital tract. It is the main cause of
      Lemierre syndrome and has also been seen in septicemia. METHODS: The patient
      presented to our institution with a 3-month history of severe lower back pain.
      Her back pain was diagnosed as vertebral osteomyelitis. Magnetic resonance images
      of the lumbar spine revealed decreased T2 signal in the L3 and L4 vertebral
      bodies. Computed tomographic scan demonstrated asymmetrical disc height loss
      between vertebral bodies L3 and L4 and associated periosteal reaction. RESULTS:
      Computed tomography-guided biopsy of vertebral bodies L3 and L4 revealed
      microorganism Fusobacterium nucleatum with the following in vitro
      susceptibilities: clindamycin <=0.5 S, metronidazole <=0.5 S, penicillin <=0.5 S,
      ertapenem <=4 S. Parenteral ertapenem, at a dose of 1 g every 24 hours for 8
      weeks in combination with oral amoxicillin and clavulanate as oral suppression
      was used as medical management. At 1-month follow-up after medical treatment, the
      patient's inflammatory markers returned to normal values, and the infection
      resolved with L3-L4 autofusion. CONCLUSION: We report a rare case of
      Fusobacterium vertebral osteomyelitis. This condition is associated with several
      comorbid and concomitant conditions including gastrointestinal complications.
      Effective treatment includes thoracolumbar orthosis bracing and intravenous
      antibiotic therapy.

PMID- 23132537
TI  - ProDisc cervical arthroplasty does not alter facet joint contact pressure during
      lateral bending or axial torsion.
AB  - STUDY DESIGN: A biomechanical study of facet joint pressure after total disc
      replacement using cadaveric human cervical spines during lateral bending and
      axial torsion. OBJECTIVE: The goal was to measure the contact pressure in the
      facet joint in cadaveric human cervical spines subjected to physiologic lateral
      bending and axial torsion before and after implantation of a ProDisc-C implant.
      SUMMARY OF BACKGROUND DATA: Changes in facet biomechanics can damage the
      articular cartilage in the joint, potentially leading to degeneration and painful
      arthritis. Few cadaveric and computational studies have evaluated the changes in
      facet joint loading during spinal loading with an artificial disc implanted.
      Computational models have predicted that the design and placement of the implant
      influence facet joint loading, but limited cadaveric studies document changes in
      facet forces and pressures during nonsagittal bending after implantation of a
      ProDisc. As such, little is known about the local facet joint mechanics for these
      complicated loading scenarios in the cervical spine. METHODS: Seven
      osteoligamentous C2-T1 cadaveric cervical spines were instrumented with a
      transducer to measure the C5-C6 facet pressure profiles during physiological
      lateral bending and axial torsion, before and after implantation of a ProDisc-C
      at that level. Rotations at that level and global cervical spine motions and
      loads were also quantified. RESULT.: Global and segmental rotations were not
      altered by the disc implantation. Facet contact pressure increased after
      implantation during ipsilateral lateral bending and contralateral torsion, but
      that increase was not significant compared with the intact condition. CONCLUSION:
      Implantation of a ProDisc-C does not significantly modify the kinematics and
      facet pressure at the index level in cadaveric specimens during lateral bending
      and axial torsion. However, changes in facet contact pressures after disc
      arthroplasty may have long-term effects on spinal loading and cartilage
      degeneration and should be monitored in vivo.

PMID- 23132539
TI  - Cervical myelopathy in patients with athetoid cerebral palsy.
AB  - STUDY DESIGN: Retrospective clinical study. OBJECTIVE: To report the surgical
      outcomes of patients with cervical myelopathy associated with athetoid cerebral
      palsy and to assess whether a halo vest is necessary for postoperative external
      immobilization. SUMMARY OF BACKGROUND DATA: Although a halo vest has remained the
      first choice for postoperative external immobilization of patients with cervical
      myelopathy associated with cerebral palsy, simplification of this method has been
      attempted in recent years. Studies focusing on postoperative external
      immobilization are rare. METHODS: Since 2001, 20 patients underwent surgery with
      posterior instrumented fusion or posterior fixation and anterior decompression
      with fusion with a year or longer follow-up. Before 2004, all patients were given
      a halo vest for postoperative external immobilization. After 2004, halo vests
      were not used, and when abnormal involuntary neck movements were severe, an
      intramuscular injection of botulinum toxin was administered before and after
      surgery. Surgical outcomes, surgical methods and complications were compared
      between the group that used a halo vest and the group that did not use a halo
      vest. RESULTS: In the halo vest group, the average Japanese Orthopedic
      Association score was 6.9 points before surgery and 9.3 points at 1-year follow
      up. The average recovery rate was 25.0%. In the group without halo vest use, the
      average Japanese Orthopedic Association score was 5.8 points before surgery and
      9.9 points at 1-year follow-up. The average recovery rate was 35.7%. The group
      without halo vest use achieved outcomes equal to those achieved in the group with
      halo vest use. The frequency of complications was less without halo vest use than
      with halo vest use. CONCLUSION: No inferiority in clinical outcomes was seen if
      postoperative halo vest use was omitted. Progress in surgical instrumentation and
      injection of botulinum toxin may explain this result.

PMID- 23132538
TI  - Tissue renin-angiotensin system in the intervertebral disc.
AB  - STUDY DESIGN: Immunohistochemical and biochemical analyses of the rat
      intervertebral disc (IVD) tissue renin-angiotensin system (tRAS). OBJECTIVE: To
      examine the expression and function of tRAS in the rat IVD. SUMMARY OF BACKGROUND
      DATA: Angiotensin II (Ang II), the major effector of tRAS, is a hormone that
      contributes to inflammation and fibrosis in many organs. The expression of tRAS
      in the rat IVD has not been determined. METHODS: tRAS expression in rat and
      bovine IVDs was examined using real-time polymerase chain reaction (rat) and
      immunohistochemistry (rat and bovine). Rat annulus fibrosus cells in monolayer
      culture were used to examine the biological role of tRAS in vitro. The effect of
      Ang II peptide on extracellular matrix metabolism was assessed by real-time
      polymerase chain reaction. RESULTS: mRNA of tRAS components, including
      angiotensin converting enzyme, Ang II, Ang II receptor type 1, Ang II receptor
      type 2, and Cathepsin D (a renin-like enzyme), was clearly confirmed by real-time
      polymerase chain reaction analysis. In rat and bovine annulus fibrosus and
      nucleus pulposus cells in monolayer culture, immunohistochemical analysis showed
      that each tRAS component was clearly expressed. In rat IVD tissues,
      immunoreactivity to each antibody for tRAS components was also observed.
      Proliferation of rat annulus fibrosus cells was mildly stimulated by Ang II
      peptide. Ang II peptide also had minor stimulatory effect on the expression of
      the extracellular matrix components, growth factors, and catabolic proteins.
      CONCLUSION: Our results demonstrate for the first time that the tRAS components
      necessary to activate tRAS have been found in the normal rat IVD at both mRNA and
      protein levels. To elucidate the association between tRAS and the process of IVD
      degeneration, the expression and function of tRAS in the human degenerated IVD
      should be examined in a future study.

PMID- 23132540
TI  - Surgical synovectomy combined with yttrium 90 in patients with recurrent joint
      synovitis.
AB  - Radiation synovectomy (RS) is one of many therapeutic options used for recurrent
      joint synovitis. Our aim was to analyze the effect of the surgical synovectomy
      combined with yttrium 90 ((90)Y) in the treatment for recurrent joint synovitis.
      A surgical combined RS procedure was used on 32 knees of 30 patients. They were
      divided into two groups. Group 1 consisted of 7 knees of 7 patients (5 women and
      2 men) with a mean age of 40.7 years in whom RS was combined with the open
      synovectomy. Group 2 consisted of 25 knees of 23 patients (21 men and 2 women)
      with a mean age of 45.5 years in whom RS was combined with the arthroscopic
      synovectomy. Arthroscopic synovectomy or open surgery biopsy was carried out for
      all cases who diagnosed of having synovitis. A scintigraphic examination was
      conducted within 24 h after the RS procedure to investigate the systemic leakage
      of (90)Y in all patients. The outcome of treatment was assessed based on self
      reporting using the visual analogue scale (VAS) of night pain, rest pain,
      activity pain, effusion, and satisfactory scores. The average follow-up period
      was 4.15 years. There was a significant difference between before and after
      treatment in terms of outcome parameters' VAS scores in both groups (p < 0.05).
      But there was no statistically significant difference between open and
      arthroscopic synovectomy groups in terms of outcome parameters (p > 0.05).
      Satisfactory outcome was excellent in 3 patients (42.8 %) in group 1 and 8
      patients (32 %) in group 2. Surgical synovectomy with combined (90)Y could treat
      recurrent joint synovitis successfully. There was no statistically significant
      difference between open and arthroscopic synovectomy techniques combined with RS
      procedure.

PMID- 23132542
TI  - CO2 laser ionization of acoustically levitated droplets.
AB  - For many analytical purposes, direct laser ionization of liquids is desirable.
      Several studies on supported droplets, free liquid jets, and ballistically
      dispensed microdroplets have been conducted, yet detailed knowledge of the
      underlying mechanistics in ion formation is still missing. This contribution
      introduces a simple combination of IR-MALDI mass spectrometry and an acoustical
      levitation device for contactless confinement of the liquid sample. The homebuilt
      ultrasonic levitator supports droplets of several millimeters in diameter. These
      droplets are vaporized by a carbon dioxide laser in the vicinity of the
      atmospheric pressure interface of a time of flight mass spectrometer. The
      evaporation process is studied by high repetition rate shadowgraphy experiments
      elucidating the ballistic evaporation of the sample and revealing strong
      confinement of the vapor by the ultrasonic field of the trap. Finally, typical
      mass spectra for pure glycerol/water matrix and lysine as an analyte are
      presented with and without the addition of trifluoracetic acid, and the
      ionization mechanism is briefly discussed. The technique is a promising candidate
      for a reproducible mass spectrometric detection scheme for the field of
      microfluidics. 

PMID- 23132541
TI  - Phosphorylation of osteopontin in osteoarthritis degenerative cartilage and its
      effect on matrix metalloprotease 13.
AB  - The purpose of this study is to observe the differences of osteopontin (OPN)
      phosphorylation in osteoarthritis (OA) cartilage and normal cartilage, and
      evaluate the possible correlations between the OPN phosphorylation and MMP-13
      expression. Degenerative cartilage (n = 29) and normal cartilage (n = 10) were
      identified by hematoxylin-eosin, safranin-O staining and modified Mankin score.
      The phosphorylation level of OPN in OA cartilage and normal cartilage was
      detected by immunoprecipitation. Chondrocytes were treated with phospho-OPN, OPN
      or buffer. Quantitative reverse transcription polymerase chain reaction (qPCR)
      and ELISA were used to assess the expression of MMP-13 in different treatments.
      The OD values of phosphorylation of OPN in normal cartilage and OA cartilage were
      137.89 +/- 10.59 and 153.52 +/- 8.80, respectively, (P = 0.000). Chondrocytes
      treated with OPN showed a higher MMP-13 expression at gene and protein level
      compared with control group. Chondrocytes treated with phospho-OPN showed the
      highest MMP-13 expression in gene and protein. In conclusion, our results
      revealed a higher phosphorylation level of OPN in OA cartilage than in normal
      cartilage. We found OPN leads to elevated expression of MMP-13 (both at gene
      level and protein level), and phospho-OPN had a more obvious upregulation effect
      on MMP-13 expression than nonphospho-OPN. Further studies are needed to reveal
      the mechanism of OPN phosphorylation on cartilage degeneration.

PMID- 23132543
TI  - Highly porous magnetite/graphene nanocomposites for a solid-state
      electrochemiluminescence sensor on paper-based chips.
AB  - Graphene-nanosheet-based highly porous magnetite nanocomposites (GN-HPMNs) have
      been prepared using a simple solvothermal method and used as an immobilization
      matrix for the fabrication of a solid-state electrochemiluminescence (ECL) sensor
      on paper-based chips. Highly porous Fe3O4 nanocrystal clusters were coated with
      acrylate and wrapped tightly on the skeleton of graphene nanosheets. The
      structures and sizes of the GN-HPMNs could be tuned by varying the proportions of
      the solvents ethylene glycol and diethylene glycol. Then, the relatively highly
      porous ones with an average diameter of about 65 nm were combined with Nafion to
      form composite films on an electrode surface for immobilization of Ru(bpy)3(2+)
      (bpy is 2,2'-bipyridine). Because of their porosity, negatively charged surface,
      and cooperative characteristics of magnetic nanomaterials and graphene, under an
      external magnetic field, the GN-HPMNs ensured effective immobilization, excellent
      electron transfer, and long-term stability of Ru(bpy)3(2+) in the composite film.
      The sensor developed exhibited excellent reproducibility with a relative standard
      deviation of 0.65% for 30 continuous cycles. It was found to be much more
      favorable for detecting compounds containing tertiary amino groups and DNAs with
      guanine and adenine. A detection limit (signal-to-noise ratio of 3) of 5.0 nM was
      obtained for tripropylamine. As an application example, 0.5 nM single-nucleotide
      mismatch could be detected. This was the first attempt to introduce magnetic
      nanomaterials and an external magnetic field into paper-based chips. The sensor
      developed has the advantages of high sensitivity, good stability, and wide
      potential applicability as well as simplicity, low cost, and good disposability.

PMID- 23132545
TI  - Monotheistic and spiritual style literature in traditional medicine's resources.
AB  - The basis for success of Iranian Gnostics, poets and scientists were moral
      teaching, attention to origin and searching for specific goals in creation of
      human and creatures as well as finding some of his essence in studying all
      phenomena regarding the creation of universe by divine attitude. There is no
      surprise that such relationship was bilateral and according to his promise to
      those who truly follow him such that he will show the right path of learning to
      human in order to obtain the secrets of life. This relationship has resulted in
      growth of famous Iranian scientists such as Rhazes, Ahvazi, Avicenna, Ferdousi
      and... at the beginning of the second millennium. Thus, goal of this research is
      to study the style of writing in original resources of traditional medicine. In
      order to increase the accuracy of this study, an electronic database version of
      traditional medicine resources has been prepared. Writing style of Alhavi book
      (by Rhazes), Kamel-al-Sanaah (by Ahvazi), Canon of Medicine (by Avicenna) and
      Zakhireye Khwarazmshahi (by Jorjani) was considered. This task was accomplished
      by searching using related key words such as God, creator, magnificent,
      omnipotent, transcendent, omniscient and many other similar words and then
      encoding them. Finally, content analysis of these words was performed. Hundreds
      of monotheistic words and many small and great texts related to monotheistic
      literature have been encountered in the literature, and some are mentioned in the
      following. Rhazes has started some parts of Alhavi by remembering the name of
      merciful God and saluting his prophets and has mentioned "God" for more than 570
      times and the word "God willing" for more than 215 times. Ahvazi has written his
      book called Kamel-al-Sanaah by using monotheistic literature, so that both
      volumes of book are started by remembering the name of God and saluting his
      prophets. In the introduction of first volume of his book, he has acknowledged
      God due to conferring logic and wisdom to human and has used the word "God" more
      than 230 times in his book. He has also referred to a famous testimony of
      Hippocrates and added some more issues in relation to medical ethics. Avicenna
      has started the Canon of Medicine in five volumes by remembering God and saluting
      his prophets. When referring to points related to having specific goal in
      structure of body organs, he immediately has praised God. Jorjani also has
      followed up the same attitude of three mentioned writers. We have found out that
      any of the Iranian poets, Gnostics and scientists who have studied nature have
      reached to the same conclusion from their own point of view, meaning, they all
      have observed permanent emergence of God in all phenomena of universe. Poets
      considered the beauties of nature, Gnostics studied mental issues and scientists
      of natural sciences explored the physiology and anatomy of human body; however,
      all of them referred to beauty, magnificent, discipline and having goal in
      creation of universe and all of its phenomena in their books. They have written
      their valuable books by benefiting monotheistic literature and have published
      their research results by inference of seeking God and paved the way for next
      generations. They experienced the usefulness of cumulative effects of
      spirituality, religion and health on performance and thereby emphasizing the need
      to incorporate spirituality and religion in teachings curriculums. 

PMID- 23132544
TI  - Milk and serum standard reference materials for monitoring organic contaminants
      in human samples.
AB  - Four new Standard Reference Materials (SRMs) have been developed to assist in the
      quality assurance of chemical contaminant measurements required for human
      biomonitoring studies, SRM 1953 Organic Contaminants in Non-Fortified Human Milk,
      SRM 1954 Organic Contaminants in Fortified Human Milk, SRM 1957 Organic
      Contaminants in Non-Fortified Human Serum, and SRM 1958 Organic Contaminants in
      Fortified Human Serum. These materials were developed as part of a collaboration
      between the National Institute of Standards and Technology (NIST) and the Centers
      for Disease Control and Prevention (CDC) with both agencies contributing data
      used in the certification of mass fraction values for a wide range of organic
      contaminants including polychlorinated biphenyl (PCB) congeners, chlorinated
      pesticides, polybrominated diphenyl ether (PBDE) congeners, and polychlorinated
      dibenzo-p-dioxin (PCDD) and dibenzofuran (PCDF) congeners. The certified mass
      fractions of the organic contaminants in unfortified samples, SRM 1953 and SRM
      1957, ranged from 12 ng/kg to 2200 ng/kg with the exception of 4,4'-DDE in SRM
      1953 at 7400 ng/kg with expanded uncertainties generally <14 %. This agreement
      suggests that there were no significant biases existing among the multiple
      methods used for analysis.

PMID- 23132546
TI  - Introduction to the themed issue 'Vitamin D update'.

PMID- 23132547
TI  - High-mobility field effect transistors based on supramolecular charge transfer
      nanofibres.
AB  - Self-assembled charge transfer supramolecular nanofibres of coronene
      tetracarboxylate (CS) and dodecyl substituted unsymmetric viologen derivative
      (DMV) behave as active channel in field effect transistors exhibiting high
      mobility. These devices work in ambient conditions and can regenerate in the
      presence of a single drop of water.

PMID- 23132548
TI  - Long-term follow-up of the Medical Research Council CLASICC trial of conventional
      versus laparoscopically assisted resection in colorectal cancer.
AB  - BACKGROUND: Laparoscopic resection is used widely in the management of colorectal
      cancer; however, the data on long-term outcomes, particularly those related to
      rectal cancer, are limited. The results of long-term follow-up of the UK Medical
      Research Council trial of laparoscopically assisted versus open surgery for
      colorectal cancer are presented. METHODS: A total of 794 patients from 27 UK
      centres were randomized to laparoscopic or open surgery in a 2:1 ratio between
      1996 and 2002. Long-term follow-up data were analysed to determine differences in
      survival outcomes and recurrences for intention-to-treat and actual treatment
      groups. RESULTS: Median follow-up of all patients was 62.9 (interquartile range
      22.9 - 92.8) months. There were no statistically significant differences between
      open and laparoscopic groups in overall survival (78.3 (95 per cent confidence
      interval (c.i.) 65.8 to 106.6) versus 82.7 (69.1 to 94.8) months respectively; P
      = 0.780) and disease-free survival (DFS) (89.5 (67.1 to 121.7) versus 77.0 (63.3
      to 94.0) months; P = 0.589). In colonic cancer intraoperative conversions to open
      surgery were associated with worse overall survival (hazard ratio (HR) 2.28, 95
      per cent c.i. 1.47 to 3.53; P < 0.001) and DFS (HR 2.20, 1.31 to 3.67; P =
      0.007). In terms of recurrence, no significant differences were observed by
      randomized procedure. However, at 10 years, right colonic cancers showed an
      increased propensity for local recurrence compared with left colonic cancers:
      14.7 versus 5.2 per cent (difference 9.5 (95 per cent c.i. 2.3 to 16.6) per cent;
      P = 0.019). CONCLUSION: Long-term results continue to support the use of
      laparoscopic surgery for both colonic and rectal cancer.

PMID- 23132549
TI  - Free-breathing 3D cardiac MRI using iterative image-based respiratory motion
      correction.
AB  - Respiratory motion compensation using diaphragmatic navigator gating with a 5 mm
      gating window is conventionally used for free-breathing cardiac MRI. Because of
      the narrow gating window, scan efficiency is low resulting in long scan times,
      especially for patients with irregular breathing patterns. In this work, a new
      retrospective motion compensation algorithm is presented to reduce the scan time
      for free-breathing cardiac MRI that increasing the gating window to 15 mm without
      compromising image quality. The proposed algorithm iteratively corrects for
      respiratory-induced cardiac motion by optimizing the sharpness of the heart. To
      evaluate this technique, two coronary MRI datasets with 1.3 mm(3) resolution were
      acquired from 11 healthy subjects (seven females, 25 +/- 9 years); one using a
      navigator with a 5 mm gating window acquired in 12.0 +/- 2.0 min and one with a
      15 mm gating window acquired in 7.1 +/- 1.0 min. The images acquired with a 15 mm
      gating window were corrected using the proposed algorithm and compared to the
      uncorrected images acquired with the 5 and 15 mm gating windows. The image
      quality score, sharpness, and length of the three major coronary arteries were
      equivalent between the corrected images and the images acquired with a 5 mm
      gating window (P-value > 0.05), while the scan time was reduced by a factor of
      1.7.

PMID- 23132550
TI  - Characterization of Afp1, an antifreeze protein from the psychrophilic yeast
      Glaciozyma antarctica PI12.
AB  - The psychrophilic yeast Glaciozyma antarctica demonstrated high antifreeze
      activity in its culture filtrate. The culture filtrate exhibited both thermal
      hysteresis (TH) and ice recrystallization inhibition (RI) properties. The TH of
      0.1  degrees C was comparable to that previously reported for bacteria and fungi.
      A genome sequence survey of the G. antarctica genome identified a novel
      antifreeze protein gene. The cDNA encoded a 177 amino acid protein with 30 %
      similarity to a fungal antifreeze protein from Typhula ishikariensis. The
      expression levels of AFP1 were quantified via real time-quantitative polymerase
      chain reaction (RT-qPCR), and the highest expression levels were detected within
      6 h of growth at -12  degrees C. The cDNA of the antifreeze protein was cloned
      into an Escherichia coli expression system. Expression of recombinant Afp1 in E.
      coli resulted in the formation of inclusion bodies that were subsequently
      denatured by treatment with urea and allowed to refold in vitro. Activity assays
      of the recombinant Afp1 confirmed the antifreeze protein properties with a high
      TH value of 0.08  degrees C.

PMID- 23132551
TI  - Phylogenetic diversity of bacterial and archaeal communities inhabiting the
      saline Lake Red located in Sovata, Romania.
AB  - Lake Red is one of the saline lakes which were formed as a consequence of salt
      massif dissolution at the foot of the Gurghiu Mountains (Central Romania) at the
      end of the nineteenth century. The lake water had approximately 15 % w/v salt
      content. Phylogenetic diversity of prokaryotes inhabiting the water and sediment
      of the lake was studied using cultivation and cultivation-independent methods
      following a sampling in spring 2009. According to the results of 16S rRNA gene
      based denaturing gradient gel electrophoresis (DGGE), the richness of Bacteria
      was higher than Archaea on the basis of the number and position of dominant bands
      in the gel. Sequences from DGGE bands were affiliated with Gammaproteobacteria
      (Halomonas and Alkalilimnicola) and Bacteroidetes (Psychroflexus) as well as
      Euryarchaeota. Cultivation from five different saline media resulted in 101
      bacterial strains of which Gammaproteobacteria (Halomonas, Marinobacter and
      Salinivibrio) were the most abundant. Firmicutes (Bacillus) and
      Alphaproteobacteria (Aurantimonas and Roseovarius) were also identified among the
      isolated strains. The 16S rRNA genes from 82 bacterial and 95 archaeal clones
      were also phylogenetically analyzed. Bacterial clones were related to various
      genera of Gammaproteobacteria (Alkalilimnicola, Alkalispirillum, Arhodomonas,
      Halomonas, Saccharospirillum), Bacteroidetes (Gracilimonas, Psychroflexus) and
      Alphaproteobacteria (Oceanicola, Roseinatronobacter, Roseovarius). All of the
      archaeal clones sequenced corresponded to a homologous cluster affiliated with
      Halopelagius.

PMID- 23132552
TI  - A qualitative identification of categories of patient participation in decision
      making by health care professionals and patients during surgical treatment.
AB  - The aim of this article is to identify how health care professionals and patients
      experience patient participation in decision-making processes in hospitals.
      Eighteen semi-structured interviews with experts from different disciplines such
      as medicine and nursing in surgical departments as well as patients who have
      undergone surgical treatment constitute the data. By content analysis four
      categories of patient participation were identified: information dissemination,
      formulation of options, integration of information, and control. To meet the
      increasing demands of patient participation, this categorization with four
      identified critical areas for participation in decision-making has important
      implications in guiding information support for patients prior to surgery and
      during hospitalization.

PMID- 23132554
TI  - HLA genotype and carbamazepine-induced cutaneous adverse drug reactions: a
      systematic review.
AB  - Carbamazepine (CBZ) therapy is associated with cutaneous adverse reactions in up
      to 10% of patients. Predisposition to these hypersensitivity reactions has been
      linked to the human leukocyte antigen (HLA) genotype. This systematic review
      determines the strength of these associations and accuracy of proposed genetic
      screening. We determined that carriage of HLA-B*1502 in Asian patients was
      associated with a pooled odds ratio (OR) of 113.4 (95% confidence interval (CI) =
      51.2-251.0, P < 1 * 10(-5)) for CBZ-induced Stevens-Johnson syndrome (SJS) and
      toxic epidermal necrolysis (TEN). A total of 461 patients would need to be
      screened for HLA-B*1502 to prevent one episode of SJS/TEN. HLA-A*3101 is
      significantly associated with all phenotypes of CBZ hypersensitivity in multiple
      ethnicities with a pooled OR of 9.5 (95% CI = 6.4-13.9, P < 1 * 10(-5)). Between
      47 and 67 patients would need to be tested for HLA-A*3101 to prevent one episode
      of hypersensitivity. Our findings suggest that HLA testing before carbamazepine
      therapy would be effective at identifying individuals at risk of hypersensitivity
      and applicable to multiple populations providing hope for prevention in the
      future.

PMID- 23132553
TI  - Impact of the CYP4F2 p.V433M polymorphism on coumarin dose requirement:
      systematic review and meta-analysis.
AB  - A systematic review and a meta-analysis were performed to quantify the
      accumulated information from genetic association studies investigating the impact
      of the CYP4F2 rs2108622 (p.V433M) polymorphism on coumarin dose requirement. An
      additional aim was to explore the contribution of the CYP4F2 variant in
      comparison with, as well as after stratification for, the VKORC1 and CYP2C9
      variants. Thirty studies involving 9,470 participants met prespecified inclusion
      criteria. As compared with CC-homozygotes, T-allele carriers required an 8.3%
      (95% confidence interval (CI): 5.6-11.1%; P < 0.0001) higher mean daily coumarin
      dose than CC homozygotes to reach a stable international normalized ratio (INR).
      There was no evidence of publication bias. Heterogeneity among studies was
      present (I(2) = 43%). Our results show that the CYP4F2 p.V433M polymorphism is
      associated with interindividual variability in response to coumarin drugs, but
      with a low effect size that is confirmed to be lower than those contributed by
      VKORC1 and CYP2C9 polymorphisms.

PMID- 23132555
TI  - Application of second-derivative fluorescence spectroscopy to monitor subtle
      changes in a monoclonal antibody structure.
AB  - In this study, the tertiary structure of a monoclonal antibody was analyzed under
      thermal and chemical stresses using second-derivative fluorescence spectroscopy.
      The effect of polyols, sucrose, and ethylene glycol on the tertiary structure of
      monoclonal antibody-U (mAb-U) (pH 7.0) was studied under thermal stress (25
      degrees C-75 degrees C). The tertiary structure of mAb-U was also analyzed upon
      chemical denaturation using urea (2.0-8.0 M). The second derivative of mAb-U
      showed three bands corresponding to the three spectral classes of tryptophan,
      class I (330 nm), class II (340 nm), and class III (350 nm). Class II was higher
      in intensity in the presence of polyols compared with the solution without any
      polyol. Thermally denatured structure of mAb-U in sucrose and ethylene glycol was
      distinctly different than that in buffer. Addition of urea resulted in a decrease
      in intensity of class I and II, and an increase in intensity of class III
      implying unfolding. This study showed that second-derivative fluorescence
      spectroscopy is an effective tool to monitor subtle alterations in the tertiary
      structure of proteins. The unfolding of a protein is reflected as an increase in
      the intensity of the polar class III accompanied with a decrease in the intensity
      of class I.

PMID- 23132556
TI  - Rhodium-catalysed asymmetric hydrogenation as a valuable synthetic tool for the
      preparation of chiral drugs.
AB  - During the last few decades, rhodium-catalysed asymmetric hydrogenation of
      diverse alkene classes has emerged as a powerful synthetic tool in the
      pharmaceutical industry, contributing to the manufacturing of chiral drugs,
      recent drug candidates for clinical trials, and major synthetic precursors of
      drugs. Numerous efficient chiral rhodium complexes, most of which are derived
      from enantiopure phosphorus ligands, have been employed for the preparation of
      chiral drugs and intermediates thereof. This review article is intended to
      provide an updated overview of the most striking contributions in this field,
      organised according to substrate class: acrylate derivatives, itaconate
      derivatives, alpha-substituted enamides, alpha-arylenol acetates, and minimally
      functionalised olefins.

PMID- 23132557
TI  - MR imaging of ectopic pregnancy with an emphasis on unusual implantation sites.
AB  - Ectopic pregnancy (EP) is a life-threatening condition and remains the leading
      cause of death in the first trimester of pregnancy, although the mortality rate
      has significantly decreased over the past few decades because of earlier
      diagnoses and great improvements in treatment. EP is most commonly located in the
      ampullary portion of the fallopian tube and rarely in unusual sites such as the
      interstitium, cervix, cesarean scar, anomalous rudimentary horn of the uterus and
      peritoneal abdominal cavity. MRI may confirm or give additional information to
      ultrasonography, which is the most user-dependent imaging modality. Magnetic
      resonance imaging can accurately localize the site of abnormal implantation. It
      could be helpful for EP patient treatment by distinguishing the ruptured and
      unruptured cases before methotrexate treatment. MRI is quite sensitive to blood
      and can identify the hemorrhage phase.

PMID- 23132558
TI  - Localization of estrogen receptor in the central lymphoid organs of chickens
      during the late stage of embryogenesis.
AB  - Immunological function in chicks is greatly affected by estrogen treatment during
      embryogenesis, but the mechanism of the estrogen effect is not fully understood.
      To elucidate the effect of estrogen on immune function, we observed estrogen
      receptor expression in the thymus and bursa of chick embryos by
      immunohistochemistry. We compared the distribution of estrogen receptor-positive
      cells with that of keratin-positive epithelial cells. Intense expression of
      estrogen receptors was detected in thymic and bursal lymphocytes. In peripheral
      lymphocytes, ER mRNA was detected by RT-PCR analysis. The results of fluorescence
      activated cell sorting analysis indicated that the estrogen receptor was
      expressed in the cytoplasm of the lymphocytes. Furthermore, intense expression of
      the estrogen receptor was also confirmed in thymic Hassall's corpuscles, bursal
      follicle-associated epithelial cells, and the bursal interfollicular epithelium.
      Our results indicate that estrogen affects the differentiation of thymic and
      bursal lymphocytes, suggesting that the underlying role for estrogen in immune
      function.

PMID- 23132559
TI  - Effects of exogenous zinc on the cellular zinc distribution and cell cycle of
      A549 cells.
AB  - As the second most abundant transition metal in humans, zinc plays essential
      roles in normal cellular biological functions, including metabolism, signalling,
      proliferation, gene expression and apoptosis. We use ZnSO(4) as a stressor in
      this study to investigate for the first time the effects of exogenous Zn(2+) on
      both the cellular distribution of zinc and zinc-related proteins and the cell
      cycle of human lung adenocarcinoma (A549) cells. The cellular distribution of
      zinc and soluble proteins was determined in the whole cell as well as in the
      cytoplasmic and nuclear fractions. Exogenous zinc in the tested exposure range (0
      100 uM) resulted in an altered cellular distribution of both zinc and the soluble
      proteins, together with total glutathione (GSx), the ratio of glutathione (GSH)
      to glutathione disulfide (GSSG) and non-protein sulphydryl (NPSH). Surprisingly,
      a turning point was observed in the re-distribution trend at a concentration of
      approximately 50 uM ZnSO(4). It is concluded that there exists a regulatory
      system in A549 cells that maintains the cellular zinc content stable in the
      presence of a certain range of extracellular zinc concentration. In addition, an
      MTT assay and flow cytometric analysis showed that the ZnSO(4) treatment led to a
      bi-phasic variation in viability and a slight fluctuation in the apoptosis of
      A549 cells. Our results will help to further elucidate zinc-related cell biology
      and biochemistry.

PMID- 23132560
TI  - Susceptibility of Listeria monocytogenes biofilms and planktonic cultures to
      hydrogen peroxide in food processing environments.
AB  - Recent studies have indicated that Listeria monocytogenes formed biofilms on the
      surface of food processing equipment, and may survive sanitization treatments.
      The purpose of this study was to compare the susceptibility of L. monocytogenes
      grown in either a biofilm or planktonic culture when exposed to hydrogen peroxide
      (H(2)O(2)). Twelve strains of biofilm-forming L. monocytogenes and their
      planktonic counterparts were treated with various concentrations of H(2)O(2) (1,
      6, and 10%), and the cell survival was then determined at 10-min exposure
      intervals. When grown as a biofilm, L. monocytogenes was significantly more
      resistant to H(2)O(2) than under planktonic culture conditions. Planktonic L.
      monocytogenes strains exhibited significantly different susceptibility to 1%
      H(2)O(2). Equally interestingly, biofilms of the 12 L. monocytogenes strains also
      inhibited different survival rates after being treated with 6 and 10% H(2)O(2).
      However, most of the biofilms recovered to a population of 2-9 log CFU/glass
      fiber filter (GFF) after a 24-h re-growth period. These results indicate that
      there was no significant correlation between the H(2)O(2) resistance of biofilm-
      and planktonic-cultured cells, and suggest that different mechanisms for the
      resistance to sanitation or disinfection underly the persistence of certain
      strains in food-processing environments.

PMID- 23132561
TI  - Japanese butterbur (Petasites japonicus) leaves increase hepatic oxidative stress
      in male rats.
AB  - We investigated the adverse effects of Japanese butterbur leaves (Petasites
      japonicus, Compositae) in male F344/DuCrj rats. The rats were fed a control diet
      or a treatment diet containing 5% butterbur leaf powder for 4 weeks. No
      differences were observed in body weight gain, food intake or feed efficiency
      between treatments, but relative liver weight in the butterbur group was
      significantly higher than that of the control group. In addition, thiobarbituric
      acid reactive substances (TBARs) and glutathione levels in the serum and liver of
      the butterbur group were higher than those of the control group. Hepatic
      glutathione reductase and glutathione S-transferase activities and mRNA
      expression in the butterbur leaf group were higher than in the control group.
      Furthermore, hepatic cytochrome 2E1 mRNA expression was higher than in the
      control group. In vitro, an acetone extract of the butterbur leaf powder showed
      the strongest increase in TBARs level in a hepatic homogenate through 4 d. Our
      findings suggest that feeding 5% butterbur leaf powder to rats can cause adverse
      effects by increasing oxidative stress.

PMID- 23132562
TI  - JJK694, a synthesized obovatol derivative, inhibits platelet activation by
      suppressing cyclooxygenase and lipoxygenase activities.
AB  - Obovatol has various biological activities, including anti-proliferative,
      neurotrophic, anti-fibrillogenic, anti-platelet, anti-fungal and anti
      inflammatory activities. In this study, we investigated the effects of JJK694, a
      synthesized obovatol derivative, on rabbit platelet activation and its molecular
      mechanisms. JJK694 significantly inhibited washed rabbit platelet aggregation and
      serotonin secretion induced by collagen and arachidonic acid, but had little
      effect on thrombin- or U46619-induced aggregation. These results suggest that
      JJK694 selectively inhibits collagen- and arachidonic acid-mediated signaling.
      JJK694 also showed a concentration-dependent decrease in cytosolic Ca(2+)
      mobilization, but it had no effect on arachidonic acid liberation. On the other
      hand, it significantly inhibited the formation of arachidonic acid metabolites,
      including thromboxane A(2) (TXA(2)), prostaglandin D(2), and 12-hydroxy-5,8,10,14
      eicosatetraenoic acid (12-HETE), by suppression of cyclooxygenase (COX)-1 and
      lipoxygenase (LOX) activities. These results indicate that JJK694 hasanti
      platelet activities through inhibition of arachidonic acid metabolite production
      by suppression of COX-1 and LOX activities.

PMID- 23132563
TI  - Effects of depletion of glutathione on abscisic acid- and methyl jasmonate
      induced stomatal closure in Arabidopsis thaliana.
AB  - Glutathione (GSH) is involved in abscisic acid (ABA)- and methyl jasmonate (MeJA)
      induced stomatal closure in Arabidopsis thaliana. In this study, we examined the
      effects of GSH-decreasing chemicals, p-nitrobenzyl chloride (PNBC), iodomethane
      (IDM), and ethacrynic acid (EA), on ABA- and MeJA-induced stomatal closure in
      Arabidopsis. Treatments with PNBC, IDM, and EA decreased GSH contents in guard
      cells. Depletion of GSH by PNBC and IDM enhanced ABA- and MeJA-induced stomatal
      closure and inhibition of light-induced stomatal opening by ABA, whereas EA did
      not enhance either ABA- and MeJA-induced stomatal closure or inhibition of light
      induced stomatal opening by ABA. Depletion of GSH did not significantly increase
      the production of the reactive oxygen species (ROS), cytosolic alkalization, or
      cytosolic Ca(2+) oscillation induced by ABA and MeJA. These results indicate that
      depletion of GSH enhances ABA- and MeJA-induced stomatal closure without
      affecting ROS production, cytosolic alkalization, or cytosolic Ca(2+) oscillation
      in guard cells of Arabidopsis.

PMID- 23132564
TI  - Anti-angiogenesis activities of novel peptide complexes: mitochondria-disruptive
      9mer peptides conjugated with the integrin alpha V beta 3-homing cyclic RGD
      motif.
AB  - RGD peptides are popular drug delivery tools in treating integrin alphaVbeta3
      expressing malignant tumors and tumor vasculature cells. We investigated the
      specific delivery and pharmacological potential of enantiomeric mitochondria
      disruptive peptides (RLYLRIGRR-NH(2), RLRLRIGRR-NH(2), ALYLAIRRR-NH(2), and
      RLLLRIGRR-NH(2)) after conjugation with an integrin alphaVbeta3-homing peptide,
      cyclic pentameric RGD peptide. The cyclic RGD-conjugated mitochondria-disruptive
      peptides exhibited specific internalization, apoptosis induction, and
      cytotoxicity against integrin alphaVbeta3-high-expressing human umbilical vein
      endothelial cells. Our findings indicate that these novel peptide complexes might
      prove good anti-angiogenesis reagents.

PMID- 23132565
TI  - Re-evaluation of milk-fat globule EGF-factor VIII (MFG-E8) as an intrinsic
      component of the mouse milk-fat globule membrane.
AB  - In lactating mammary glands, milk fat is secreted as fat globules surrounded by a
      cell plasma membrane containing characteristic membrane-associated proteins.
      Among these, butyrophilin has been shown to be specific and intrinsic to the fat
      globule membrane, whereas milk-fat globule EGF-factor VIII (MFG-E8) is uncertain.
      We characterized in the present study MFG-E8 in milk fat globules and in the
      culture medium of HC11 mammary epithelial cells. MFG-E8 was immunologically
      detected in the mammary tissues of both pregnant and lactating mice. Double
      immunofluorescence staining for MFG-E8 and butyrophilin showed diversity in the
      MFG-E8-staining intensity among different fat globules in milk. HC11 cells
      secreted monomeric MFG-E8 with phosphatidylserine-binding activity, despite no
      fat globules being detected in the cells. This secretion was upregulated by not
      only prolactin but also by insulin or EGF. These results suggest that milk MFG-E8
      was not equally present among fat globules and not necessarily intrinsic to the
      fat globules.

PMID- 23132566
TI  - Production potency of folate, vitamin B(12), and thiamine by lactic acid bacteria
      isolated from Japanese pickles.
AB  - We investigated the extracellular production of folate, vitamin B(12), and
      thiamine in cultures of lactic acid bacteria (LAB) isolated from nukazuke, a
      traditional Japanese pickle, and the relationships between the vitamin production
      and such properties of LAB as tolerance to salts, ethanol, etc. Among the 180
      isolates of LAB, two strains of Lactobacillus (Lb.) sakei and a strain of Lb.
      plantarum extracellularly produced high levels of folate (about 100 ug/L). A
      strain of Lb. coryniformis and one of Lb. plantarum produced about 2 ug/L of
      vitamin B(12), although the level was not high. No isolates produced a high level
      of thiamine. The type cultures of LBA (53 strains) did not show any higher
      production of these vitamins. Some isolates showed tolerance to high
      concentrations of salts and alcohol, and low initial pH. No significant
      relationships between folate or vitamin B(12) productions and these properties of
      LAB were apparent.

PMID- 23132567
TI  - Construction of an artificial pathway for isobutanol biosynthesis in the cytosol
      of Saccharomyces cerevisiae.
AB  - To increase isobutanol production in Saccharomyces cerevisiae, the valine
      biosynthetic pathway was activated by overexpression of the relevant enzymes in
      the mitochondria and the cytosol. Native mitochondrial enzymes were overepxressed
      in the cytosol by deleting the mitochondrial transit peptides. The metabolically
      engineered S. cerevisiae possessing the cytosolic pathway showed increased
      isobutanol production (63 +/- 4 mg/L).

PMID- 23132568
TI  - Subcellular and subnuclear distribution of high-light responsive serine/arginine
      rich proteins, atSR45a and atSR30, in Arabidopsis thaliana.
AB  - Here, we demonstrated the involvement of the domains in Arabidopsis high-light
      responsive serine/arginine-rich (SR) and SR-like proteins, atSR30 and atSR45a,
      respectively, in subcellular and subnuclear distribution using a series of
      structural domain-deleted mutants. Judging from the localization of the
      transiently expressed domain-deleted mutants in onion epidermal cells, the C
      terminal low complexity domain rich in arginine-serine repeats (C-RS) domain of
      atSR30 appeared to be necessary for the nuclear localization. On the other hand,
      the N-terminal RS (N-RS) domain of atSR45a was necessary for the accurate nuclear
      localization, although the N- or C-RS domain alone was sufficient for the nuclear
      speckled organization. The phosphorylation of RS domains of atSR45a is irrelevant
      to the regulation of its localization. atSR45a and atSR30 were co-localized in
      the speckles, suggesting their collaborative roles in the regulation of
      alternative splicing events.

PMID- 23132569
TI  - Heterologous expression of corn cystatin in soybean and effect on growth of the
      stink bug.
AB  - The bean bug (Riptortus clavatus) is a serious insect pest of soybean. Corn
      (maize) cystatin strongly inhibited the activity of its digestive cysteine
      proteinase. Heterologous expression of corn cystatin in soybean seeds inhibited
      the insect's proteases, but not its growth.

PMID- 23132570
TI  - Isolation and characterization of a novel non-selective beta-toxin from the venom
      of the scorpion Isometrus maculatus.
AB  - Scorpion venom is composed of a number of peptides, many of which show
      neurotoxicity. The Isometrus maculatus scorpion, belonging to the Buthidae
      family, is found in many tropical regions, including the southern islands of
      Japan, but there have been no reports on the isolation of toxins from its venom
      affecting sodium channels. We isolated in this study a novel toxin, Im-2, from
      the I. maculatus venom. Im-2 induced paralysis in crickets after injecting 20
      ug/g of body weight. Im-2 also induced lethality in mice after an
      intracerebroventricular injection, indicating that Im-2 had non-selective
      toxicity between insects and mammals. Im-2 consists of 68 amino acids cross
      linked by 4 disulfide bonds, and has sequence similarity to scorpion beta-toxins
      that have been reported to affect the sodium channels of both insects and
      mammals. The toxic symptoms caused by Im-2 suggest that it acted on the nervous
      system and shared the action mechanism(s) with sequence-homologous beta-toxins.

PMID- 23132571
TI  - PhiC31 integrase mediates efficient site-specific integration in sheep
      fibroblasts.
AB  - PhiC31 integrase, a site-specific recombinase, can effectively mediate the
      integration of foreign genes bearing an attB sequence into pseudo attP sites of
      genomes in human, mouse, and Drosophila cells. In this study, we measured PhiC31
      integrase-mediated homologous recombination between attB and pseudo attP sites in
      sheep cells. The integration efficiency of the EGFP expression cassette with the
      attB sequence increased at least 2-fold in sheep fibroblasts. Three pseudo-attP
      sites were identified in the sheep genome, located in the intergenic regions on
      chromosomes 4, 13, and 7 respectively. Moreover, the transgene that was
      integrated at the three pseudo attP sites exhibited high levels of expression.
      Our study indicates that the PhiC31 integrase system provides an efficient
      integration tool for genetic engineering of the sheep genome.

PMID- 23132572
TI  - Improvement of gene targeting in Aspergillus nidulans with excess non-homologous
      fragments.
AB  - Efficiency of gene targeting was increased more than 10-fold when an excess molar
      ratio of non-homologous fragments was added in the transformation of Aspergillus
      nidulans. In the targeted transformants, integration of such fragments into the
      host chromosome was a rare event. Hence, our approach proved practical in terms
      of producing successful targeting events without disturbing the host chromosomes.

PMID- 23132573
TI  - A tobacco CBL-interacting protein kinase homolog is involved in phosphorylation
      of the N-terminal domain of the cucumber mosaic virus polymerase 2a protein.
AB  - The replication and transcription of cucumber mosaic virus (CMV) are catalyzed by
      multi-protein complex RNA-dependent RNA polymerase (RdRp), which is composed of
      the viral-encoded 1a and 2a proteins with host factors. We have reported that the
      N-terminal region of the polymerase 2a protein, composed of 126 amino acids, is
      required for interaction with the helicase 1a protein, and that the
      phosphorylation of the region abrogated interaction with the 1a protein,
      suggesting a mechanism of resistance in host plants against viral infection.
      Here, we found that three protein 2a kinases, of 60, 55, and 38 kDa, co-purified
      with the tobacco membrane fraction in an in-gel kinase assay. By yeast two-hybrid
      library screening using the N-terminal 126 amino acids of 2a as a bait, we
      identified CBL-interacting protein kinase 12 (NtCIPK12) corresponding to 55 kDa
      protein 2a kinase. The bacterially expressed protein kinase showed protein 2a
      kinase (t2aK) activity in vitro. We found that NtCIPK12 stabilized upon CMV
      infection at the post-translational level, and accumulated more heavily to the
      membrane than in the cytosol.

PMID- 23132575
TI  - Freeze-dried royal jelly maintains its developmental and physiological
      bioactivity in Drosophila melanogaster.
AB  - Royal jelly (RJ), a honeybee-derived product, has been found to possess
      developmental and physiological bioactivity in the fruit fly, Drosophila
      melanogaster, but little is known about the in vivo bioactivity of freeze-dried
      RJ (FDRJ) powder, which is another form of RJ processed for human use. To address
      this, we used Drosophila as a model animal to examine the effects of FDRJ in
      multicellular organisms. When flies were reared on food supplemented with FDRJ,
      the developmental time from larva to adult was shortened, the adult male lifespan
      was prolonged, and female fecundity was increased without any significant
      morphological alterations. Moreover, the expression of dilp5, an insulin-like
      peptide, its receptor InR, and the nutrient sensing molecule TOR, the target of
      rapamycin, was significantly increased in FDRJ-fed female flies as compared with
      ones reared on standard and on protein-enriched food. These findings suggest that
      like RJ, FDRJ maintains its bioactivity even after processing from RJ, what is
      expected to have bioactivity for multicellular organisms, including humans.

PMID- 23132574
TI  - Enzymatic assay for D-aspartic acid using D-aspartate oxidase and oxaloacetate
      decarboxylase.
AB  - An enzymatic assay system for D-Asp was established using D-aspartate oxidase and
      oxaloacetate decarboxylase. In this system, D-Asp is converted to pyruvate, which
      is determined fluorometrically with 1,2-diamino-4,5-methylenedioxybenzene. This
      method makes possible D-Asp measurement at the micromolar level. The D-Asp
      contents of an edible brown alga, Hijika fusiforme, a lactic acid bacteria
      beverage, and pig testis were determined by the method.

PMID- 23132576
TI  - Estimation of the gelatinization temperature of noodles from water sorption
      curves under temperature-programmed heating conditions.
AB  - A novel method in which the water sorption curve is observed under linearly
      temperature-raising conditions was proposed to estimate the gelatinization
      temperature of starch-containing foods, it was applied in an estimation of the
      gelatinization temperatures of dried noodles. The gelatinization temperatures of
      two kinds of spaghetti, dried at high and low temperature, were 52.3 and 53.1 
      degrees C, and those of udon, kishimen, juwari-soba, hachiwari-soba, so-called
      common soba, Malony((r)), and kuzukiri were 57.0, 57.8, 61.1, 59.6, 57.4, 48.4,
      and 49.1  degrees C. The gelatinization temperatures estimated by the method were
      between the onset and peak temperatures obtained by differential scanning
      calorimetric measurement.

PMID- 23132577
TI  - A Caenorhabditis elegans insulin-like peptide, INS-17: its physiological function
      and expression pattern.
AB  - The insulin/insulin-like growth factor-1 signaling pathway of Caenorhabditis
      elegans regulates larval diapause and adult lifespan through the sole insulin
      receptor-like protein, DAF-2. In the present study, the physiological function
      and expression pattern of INS-17, one of the C. elegans insulin-like peptides,
      were examined by disruption and overexpression of the gene, and by the use of a
      reporter gene. INS-17 might function as a DAF-2 antagonist in the regulation of
      larval diapause, but not of the adult lifespan. The reporter protein was
      intensively expressed during larval diapause. It showed a drastic decrease in
      amount after larval diapause, which matches well the physiological function of
      INS-17.

PMID- 23132578
TI  - Role of lumenal domain on intracellular localization of tobacco membrane-anchored
      prolyl 4-hydroxylase.
AB  - NtP4H1.1 is a Golgi-localizing type II integral membrane protein. Mutations in
      the cytoplasmic tail direct the protein to the endoplasmic reticulum (ER). We
      expressed a GFP fusion protein containing the mutant tail and the transmembrane
      region in tobacco BY-2 cells, and found that the protein localized in the Golgi.
      Therefore NtP4H1.1 contains multiple targeting information in different regions.

PMID- 23132579
TI  - Effective Friedel-Crafts acylation of biotin acid chloride in
      trifluoromethanesulfonic acid.
AB  - Biotin is one of the most useful tags in (bio)analytical science due to its
      specific interaction with avidin, but is not easy to convert because of its low
      solubility in most solvents. Friedel-Crafts acylation of biotin acid chloride in
      triflic acid was examined, and the synthesized derivatives had stronger affinity
      to avidin than biotin in a binding assay using 2-(4'-hydroxyphenylazo)benzoic
      acid.

PMID- 23132580
TI  - The role of acetylation in the subcellular localization of an oncogenic isoform
      of translation factor eIF5A.
AB  - Mammalian cells express two isoforms of eIF5A, eIF5A1 and eIF5A2, but little is
      known about the function of eIF5A2. Here we report that eIF5A2 is reversibly
      acetylated at lysine-47. HDAC6 and SIRT2 were identified as the enzymes
      responsible for deacetylating eIF5A2. Analysis using acetylation-deficient
      mutants indicated that acetylation regulates the subcellular localization of
      eIF5A2.

PMID- 23132581
TI  - Rat stem-cell leukemia gene expression increased during testis maturation.
AB  - We found that stem-cell leukemia (SCL), also known as T cell acute-lymphocytic
      leukemia (Tal-1) gene expression, was upregulated in the maturing rat testis.
      Strong expression of Tal-1 was detected in the normal maturing rat testis by
      Northern blotting. Western blotting revealed the protein size to be about 34 kDa.
      Protein expression was wide-spread in spermatocytes, spermtids and spermatogonia
      in accordance with the seminiferous epithelium cycle, as determined by an
      analysis of immunohistochemistry. Gene expression of Tal-1 regulatory gene,
      NKX3.1, was negatively correlated with Tal-1 expression. Human Tal-1 expression
      in the maturing testis as well as in bone marrow was observed, which suggests
      that the gene product is a novel cancer-testis antigen candidate. Taken together,
      TAL-1 may be involved in cell division, morphological changes, and the
      development of spermatogenic cells in the normal rat testis.

PMID- 23132582
TI  - Identification of the plant origin of propolis from Jeju Island, Korea, by
      observation of honeybee behavior and phytochemical analysis.
AB  - Propolis collected on Jeju Island, Korea, contains characteristic components not
      present in propolis from other regions. Hence, the plant origin of the propolis
      from Jeju Island can be expected to be a novel plant. To identify the plant
      origin of this propolis, first we observed honeybee behavior, and found them
      collecting the resin from Angelica keiskei. Then comparative analyses of chemical
      and biological properties of the resin from the plant and propolis from hives of
      nearby apiaries were performed. Alcoholic extracts showed entirely identical HPLC
      profiles and closely similar antioxidant activities. These results indicate that
      A. keiskei is the plant origin of the propolis from Jeju Island, Korea.

PMID- 23132583
TI  - Female sex pheromone secreted by Carmenta mimosa (Lepidoptera: Sesiidae), a
      biological control agent for an invasive weed in Vietnam.
AB  - Larvae of the clearwing moth, Carmenta mimosa (Lepidoptera: Sesiidae), bore into
      the trunk of Mimosa pigra L., which is one of the most invasive weeds in Vietnam.
      GC-EAD and GC-MS analyses of a pheromone gland extract revealed that the female
      moths produced (3Z,13Z)-3,13-octadecadienyl acetate. A lure baited with the
      synthetic acetate alone successfully attracted C. mimosa males in a field test.
      While the addition of a small amount of the corresponding alcohol did not
      strongly diminish the number of captured males, a trace of the aldehyde
      derivative or the (3E,13Z)-isomer markedly inhibited the attractiveness of the
      acetate. The diurnal males were mainly attracted from 6:00 am to 12:00 am.

PMID- 23132584
TI  - A derivative of L-allo threonine alleviates 2,4-dinitrofluorobenzene-induced
      atopic dermatitis indications.
AB  - LX519290, a synthetic derivative from a combinatorial chemistry library, has been
      screened for anti-atopic activity, but its biological activities have not yet
      been elucidated. To assess whether LX519290 has the potential to lessen 2,4
      dinitrofluorobenzene-induced atopic dermatitis symptoms in mice, first we
      sensitized the skin in the dorsal neck of C57BL/6 mice and re-sensitized the ear
      skin to determine the ear thickness. Then, we tested to determine whether
      LX519290 affect atopic dermatitis symptoms in vivo. The results indicate that
      LX519290 significantly mitigated inflammation indications including ear
      thickness, total T-cell numbers, and eosinophils. Moreover, the treatment
      drastically inhibited the levels of mediators such as interleukin-17E and
      histamine by 52% and 37% of control, respectively. Taken together, the data
      suggest that LX519290 can alleviate atopic parameters in mice.

PMID- 23132585
TI  - Geographic origins of Korean and Chinese kimchi determined by multiple elements.
AB  - An elemental analysis was performed on 30 Korean and Chinese kimchi samples in
      combination with strontium (Sr) isotope ratio measurements to develop a method
      for tracing the geographic origins of Korean and Chinese kimchi. We found a
      distinct difference between Korean and Chinese kimchi in such specific elements
      as K, Na, Ca, Ba, Sr, Zn, Li, and Sc, but no significant difference in the Sr
      isotope ratio. A comparative analysis was performed with washed kimchi
      (containing no submaterial) and unwashed kimchi to evaluate the effect of
      submaterials on the determination of geographic origin. A linear discriminant
      analysis provided a clear distinction between Korean and Chinese kimchi. The
      results indicate that combining multi-elemental and statistical analyses has the
      potential to determine the geographic origins of such processed food as kimchi.

PMID- 23132586
TI  - Wx/ae double-mutant brown rice prevents the rise in plasma lipid and glucose
      levels in mice.
AB  - A wx/ae double-mutant rice is generated by crossing waxy mutant and amylose
      extender mutant in rice. Wx/ae brown rice contains highly beneficial nutrients
      for lipid and glucose metabolism, including resistant starch, dietary fiber, and
      gamma-oryzanol, when compared to Koshihikari brown rice, the non-waxy japonica
      cultivar. To examine the effects of wx/ae brown rice on glucose and lipid
      metabolism, type 2 diabetic NSY/Hos mice were fed a high-fat diet containing 25%
      of wx/ae brown rice or Koshihikari brown rice for 10 weeks. The plasma total
      cholesterol, non-high-density lipoprotein cholesterol, triglyceride, and non
      esterified fatty acid levels of the wx/ae group were significantly lower than
      those of the Koshihikari group. Moreover, the fasting blood glucose level and
      pathological score of glycosuria of the wx/ae group were also significantly lower
      than those of the Koshihikari group. These results indicate that wx/ae brown rice
      has the potential to prevent the rise in plasma lipid and glucose levels.

PMID- 23132587
TI  - Macrophage recognition of thiol-group oxidized cells: recognition of carbohydrate
      chains by macrophage surface nucleolin as apoptotic cells.
AB  - The mechanism was investigated for macrophage recognition of cells oxidized by
      diamide, a thiol group-specific oxidizing reagent. Jurkat cells exposed to
      various concentrations of diamide were recognized by macrophages, the cells
      exposed to 25 uM diamide being best recognized. CD43, a major glycoprotein on the
      Jurkat cell surface, tended to form clusters upon diamide oxidization, and
      pretreating Jurkat cells with the anti-CD43 antibody inhibited macrophage
      binding. This indicates that macrophages appeared to recognize CD43. Sodium
      dodecyl sulfate polyacrylamide gel electrophoresis and a Western blot analysis of
      CD43 of the diamide-oxidized cells showed no increase in the amount of cross
      linked CD43 compared with control cells, indicating that cross-linking of CD43 by
      a disulphide bond was not involved in the clustering. Both CD43 clustering and
      binding of the oxidized cells to macrophages was prevented by the caspase
      inhibitor, benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethyl ketone (Z-VAD-fmk),
      suggesting that the oxidized and macrophage-bound cells were undergoing
      apoptosis. A closer examination revealed that the caspase-3 activity, chromatin
      condensation, and DNA fragmentation in Jurkat cells were all increased by
      oxidation. The macrophage receptor involved in the binding appeared to be the
      cell-surface protein, nucleolin; an anti-nucleolin antibody treatment inhibited
      the binding. These results suggest that thiol group-oxidized cells underwent
      early apoptosis and were recognized by nucleolin on macrophages as early
      apoptotic cells.

PMID- 23132588
TI  - In vivo and in vitro studies on the absorption characteristics of beta
      cryptoxanthin in the intestine.
AB  - beta-Cryptoxanthin (beta-CRX) is a carotenoid abundantly present in the Satsuma
      mandarin (Citrus unshiu Marc.), one of the most popular fruits in Japan, and it
      is reported to have several health benefits. Although it is thought to have
      higher bioavailability than other carotenoids, the usual daily intake is small,
      and a good method to improve its bioavailability is needed. Hence we studied the
      effect of emulsification on the absorption characteristics of beta-CRX in the
      intestine. Human trials showed that its serum transfer efficiency was
      statistically higher in the emulsified formulation than in fresh Satsuma mandarin
      juice. Caco-2 permeability studies indicated that emulsifiers preferentially
      accelerate the absorption of the non-esterified form of beta-CRX, suggesting that
      emulsification is more effective for free beta-CRX. This information might be
      useful to improve the efficiency of beta-CRX serum transfer, as well as to
      increase the health benefits of beta-CRX.

PMID- 23132589
TI  - Overexpression of a rice TIFY gene increases grain size through enhanced
      accumulation of carbohydrates in the stem.
AB  - Screening of rice full-length cDNA overexpressing (FOX) lines allowed the
      identification of a TIFY gene, TIFY11b, as a growth-promoting gene whose
      overexpression increased plant height and seed size. The grains of TIFY11b
      overexpressing plants exceeded those of non-transformants in length, width and
      thickness, resulting in 9-21% increases in grain weight. The increase was
      achieved by overexpressing the gene in the whole plant body, but not by seed
      restricted expression, indicating that seed enlargement is attributable to
      overexpression in vegetative organs such as the leaf. The whole-body
      overexpressing plants developed longer leaves along with higher levels of starch
      and sucrose in the leaf sheath and culm at the heading stage than the non
      transformants. Although overexpression of TIFY11b did not alter the
      photosynthetic rate per leaf area before and after heading, it caused an
      accumulation of higher levels of the carbohydrate assimilate, probably due to
      increased photosynthesis per plant, suggesting that the increase in grain size
      and weight is attained by enhanced accumulation and translocation of the
      carbohydrate in the culms and leaf sheaths of the transgenic plants. Thus,
      TIFY11b is a novel grain-size increasing gene.

PMID- 23132590
TI  - Enhancement of the enzymatic activity of Escherichia coli acetyl esterase by a
      double mutation obtained by random mutagenesis.
AB  - A double mutant of Escherichia coli acetyl esterase (EcAE) with enhanced
      enzymatic activity was obtained by random mutagenesis using error-prone PCR and
      screening for enzymatic activity by observing halo formation on a tributyrin
      plate. The mutant contained Leu97Phe (L97F) and Leu209Phe (L209F) mutations.
      Single mutants L97F and L209F were also constructed and analyzed for kinetic
      parameters, as well as double mutant L97F/L209F. Kinetic analysis using p
      nitrophenyl butyrate as substrate indicated that the k(cat) values of L97F and
      L97F/L209F were larger than that of the wild-type enzyme, by 8.3-fold and 12-fold
      respectively, whereas no significant change was observed in the k(cat) value of
      L209F. The K(m) values of L209F and L97F/L209F were smaller than that of the wild
      type enzyme, by 2.9-fold and 2.4-fold respectively, whereas no significant change
      was observed in the K(m) value of L97F. These results indicate that a combination
      of an increase in k(cat) values due to the L97F mutation and a decrease in K(m)
      value due to the L209F mutation renders the k(cat)/K(m) value of the double
      mutant enzyme 29-fold higher than that of the wild-type enzyme.

PMID- 23132591
TI  - Aloe vera gel extract attenuates ethanol-induced hepatic lipid accumulation by
      suppressing the expression of lipogenic genes in mice.
AB  - We have previously reported that Aloe vera gel had hypoglycemic activity and anti
      obesity effects, although the effect on alcoholic fatty liver was unclear. We
      examined in this present study the effect of an Aloe vera gel extract (AVGE) on
      hepatic lipid metabolism by using an ethanol-induced transient fatty liver mouse
      model. Ethanol (3 g/kg of mouse weight) was orally administered to induce an
      accumulation of triglyceride (TG) and increase the mRNA expression of such
      lipogenic genes as sterol regulatory element-binding protein-1 (SREBP-1) and
      fatty acid synthase (FASN) in the liver. Although ethanol ingestion caused a 5.4
      fold increase in liver TG, pre-treating with AVGE (1 mg/kg/d) for 1 week
      significantly suppressed this elevation of the ethanol-induced liver TG level.
      The expression of lipogenic genes was also lower in the AVGE pre-treatment group
      than in the control group. This inhibitory effect on the ethanol-induced
      accumulation of TG was attributed to a reduction in the expression of lipogenic
      genes that were increased by ethanol.

PMID- 23132592
TI  - Accuracy and concordance of anthropometry for measuring regional fat distribution
      in adults aged 20-55 years.
AB  - OBJECTIVES: This study aimed to assess the accuracy and concordance of
      anthropometrically derived prediction equations for the estimation of regional
      fat mass (FM) distribution. METHODS: Sixty-two white males and 50 females with a
      large range of age (20-55 years) and BMI (16.6-33.4 kg/m(2)) were included. Whole
      body dual energy X-ray absorptiometry (DXA) scans were acquired and
      anthropometric prediction equations for regional FM were developed and cross
      validated. On the basis of the total sample two anthropometrically derived
      indices of FM distribution [Formula: see text] ratio and [Formula: see text]
      ratio were compared with their DXA analogues. RESULTS: In both sexes multiple
      linear regression models predicted the regional DXA fat masses with good accuracy
      (P < 0.001). In men mean bias (limits of agreement) were: -6.8 g (-535,364) for
      FM(arms), 65 g (-1921,2052) for FM(trunk), -21 g (-1374,1332) for FM(legs), -0.2%
      (-5.0,4.7) for %FM(trunk) and -0.5% (-6.8,5.8) for %FM(legs). In women mean
      difference (limits of agreement) were: -86 g (-463,450) for FM(arms), 30 g (
      1784,1844) for FM(trunk), -278 g (-1782,1227) for FM(legs), 0.4% (-5.5,6.3) for
      %FM(trunk), and 0.3% (-8.3,8.9) for %FM(legs). No systematic (constant and
      proportional) differences between methods for the determination of FM
      distribution ratios were found, suggesting method interchangeability. The
      concordance for subject classification based on t-scores according to the
      National Health and Nutrition Examination Survey (NHANES) was significant (P <
      0.001), with substantial agreement for [Formula: see text] ratio (kappa(w) =
      0.80) and [Formula: see text] ratio (kappa(w) = 0.75). CONCLUSION: Anthropometric
      variables offer promise to the development of simple, noninvasive, and
      inexpensive screening to identify individuals with abnormal FM distribution. The
      anthropometrically derived indices of FM distribution demonstrate sufficient
      accuracy for clinical use. Am. J. Hum. Biol., 2013. (c) 2012 Wiley Periodicals,
      Inc.

PMID- 23132593
TI  - Tie2(+)  bone marrow endothelial cells regulate hematopoietic stem cell
      regeneration following radiation injury.
AB  - Hematopoietic stem cells (HSCs) reside in proximity to bone marrow endothelial
      cells (BM ECs) and maintenance of the HSC pool is dependent upon EC-mediated c
      kit signaling. Here, we used genetic models to determine whether radioprotection
      of BM ECs could facilitate hematopoietic regeneration following radiation-induced
      myelosuppression. We developed mice bearing deletion of the proapoptotic
      proteins, BAK and BAX, in Tie2(+) ECs and HSCs (Tie2Bak/Bax(Fl/-) mice) and
      compared their hematopoietic recovery following total body irradiation (TBI) with
      mice which retained Bax in Tie2(+) cells. Mice bearing deletion of Bak and Bax in
      Tie2(+) cells demonstrated protection of BM HSCs, preserved BM vasculature, and
      100% survival following lethal dose TBI. In contrast, mice that retained Bax
      expression in Tie2(+) cells demonstrated depletion of BM HSCs, disrupted BM
      vasculature, and 10% survival post-TBI. In a complementary study,
      VEcadherinBak/Bax(Fl/-) mice, which lack Bak and Bax in VEcadherin(+) ECs, also
      demonstrated increased recovery of BM stem/progenitor cells following TBI
      compared to mice which retained Bax in VEcadherin(+) ECs. Importantly, chimeric
      mice that lacked Bak and Bax in HSCs but retained Bak and Bax in BM ECs displayed
      significantly decreased HSC content and survival following TBI compared to mice
      lacking Bak and Bax in both HSCs and BM ECs. These data suggest that the
      hematopoietic response to ionizing radiation is dependent upon HSC-autonomous
      responses but is regulated by BM EC-mediated mechanisms. Therefore, BM ECs may be
      therapeutically targeted as a means to augment hematopoietic reconstitution
      following myelosuppression.

PMID- 23132594
TI  - Fludarabine and cytarabine in patients with relapsed acute myeloid leukemia
      refractory to initial salvage therapy.
AB  - The most effective regimen for relapsed acute myeloid leukemia (AML) patients who
      do not achieve complete remission (CR) after a course of salvage therapy has not
      been established. We evaluated the efficacy and toxicity of fludarabine and
      cytarabine in patients with AML in first relapse who did not respond to a course
      of salvage chemotherapy with mitoxantrone and etoposide. CR was achieved in 39 %
      of treated patients, and in 47 % of patients with a favorable/intermediate-risk
      karyotype. The median overall survival was 4.75 months. The median survival for
      patients achieving CR with fludarabine-cytarabine was significantly higher than
      for those who did not respond to therapy (9.6 vs. 4.5 months, P = 0.04). Our data
      suggest that the fludarabine-cytarabine regimen merits further investigation in
      relapsed AML patients with favorable or intermediate-risk karyotype with
      persistent leukemia after a course of salvage therapy.

PMID- 23132595
TI  - Passing a baton to the next generation.

PMID- 23132597
TI  - Investigation of interstitial hydrogen and related defects in ZnO.
AB  - We investigate defects in bulk zinc oxide by performing embedded cluster
      calculations within the density functional theory using the PBE functional. We
      obtain and discuss equilibrium structures and vibrational spectra of interstitial
      hydrogen species and of hydrogen complexes at zinc vacancies and at
      substitutional atoms like copper, beryllium, manganese and calcium in zinc
      positions. All of these defects differ in their vibrational frequencies which can
      be assigned to existing experimental data with an agreement that surpasses the
      results of earlier calculations within the local (spin) density approximation.
      This leads to a better understanding of these bulk defects and helps to answer
      some open questions, as e.g. the assignment of a signal observed in infra red
      spectra at 3326 cm(-1). Furthermore, the computed vibrational spectra may serve
      as a benchmark and assist in the interpretation of future experimental results.

PMID- 23132598
TI  - More experienced doctors incur lower treatment costs, finds study.

PMID- 23132596
TI  - Low incidences of acute and chronic graft-versus-host disease after unrelated
      bone marrow transplantation with low-dose anti-T lymphocyte globulin.
AB  - Anti-T lymphocyte globulin (ATG) is commonly used as prophylaxis for graft-versus
      host disease (GVHD), especially in patients who are at high risk of GVHD. The
      appropriate dosage of ATG in Japan has not yet been assessed. We therefore
      conducted a nationwide survey of patients who received ATG-Fresenius as GVHD
      prophylaxis for unrelated bone marrow transplantation (uBMT). A total of 86
      patients were identified (median age 31 years, range 1-68). The median total dose
      of ATG was 10 mg/kg. The cumulative incidence of neutrophil engraftment was 90 %.
      The probability of 2-year overall survival (OS) was 67 %. The cumulative
      incidence of 2-year non-relapse mortality was 25 %. The incidences of grade II-IV
      and grade III-IV acute GVHD were 20 and 8 %, respectively. The incidences of
      chronic and extensive chronic GVHD were 19 and 8 %, respectively. In adult
      patients, there was a reduction of acute GVHD with high-dose ATG (>10 mg/kg),
      which did not reach statistical significance. In conclusion, the addition of low
      dose ATG to GVHD prophylaxis in Japanese patients who received uBMT resulted in
      decreased incidences of both acute and chronic GVHD without compromising OS. The
      effects of low-dose ATG should be assessed in a prospective clinical trial.

PMID- 23132599
TI  - NHS Constitution is "patchy, low key, and inconsistent," says review.

PMID- 23132600
TI  - Family accuses hospital of putting a "do not resuscitate" notice in patient's
      notes without her knowledge.

PMID- 23132601
TI  - Health professionals defend the Liverpool care pathway.

PMID- 23132602
TI  - Only half of people with diabetes receive all the tests they need, report says.

PMID- 23132603
TI  - Development of health systems and universal coverage should be evidence based,
      says WHO.

PMID- 23132604
TI  - Reading your own lips: common-coding theory and visual speech perception.
AB  - Common-coding theory posits that (1) perceiving an action activates the same
      representations of motor plans that are activated by actually performing that
      action, and (2) because of individual differences in the ways that actions are
      performed, observing recordings of one's own previous behavior activates motor
      plans to an even greater degree than does observing someone else's behavior. We
      hypothesized that if observing oneself activates motor plans to a greater degree
      than does observing others, and if these activated plans contribute to
      perception, then people should be able to lipread silent video clips of their own
      previous utterances more accurately than they can lipread video clips of other
      talkers. As predicted, two groups of participants were able to lipread video
      clips of themselves, recorded more than two weeks earlier, significantly more
      accurately than video clips of others. These results suggest that visual input
      activates speech motor activity that links to word representations in the mental
      lexicon.

PMID- 23132606
TI  - Automatic activation of attribute knowledge in heuristic inference from memory.
AB  - In memory-based decision making, people often rely on simple heuristics such as
      take-the-best (TTB; Gigerenzer & Goldstein, Psychological Review, 103, 650-669,
      1996), which processes information about the alternatives sequentially and stops
      processing as soon as a decision can be made. In this article, we examine the
      memory processes associated with TTB--in particular, to what degree the selective
      memory retrieval of relevant information required by TTB is accompanied by
      automatic activation of associated but irrelevant information. To address this
      question, we studied the fan effect (Anderson, Cognitive Psychology, 6, 451-474,
      1974), which is assumed to arise from automatic spread of activation, in
      inferences from memory. Participants were instructed to use TTB when making
      decisions about objects on the basis of previously memorized attribute
      information. Both the number of attributes required by TTB and the number of
      attributes associated with an object (i.e., fan level) were manipulated. As it
      turned out, response times and the correct execution of TTB were a function not
      only of the number of required attributes, but also of the number of associated
      attributes. This suggests that information that TTB "ignores" is nevertheless
      activated in memory.

PMID- 23132607
TI  - The unbearable articulatory nature of naming: on the reliability of word naming
      responses at the item level.
AB  - Single-word naming is one of the most widely used experimental paradigms for
      studying how we read words. Following the seminal study by Spieler and Balota
      (Psychological Science 8:411-416, 1997), accounting for variance in item-level
      naming databases has become a major challenge for computational models of word
      reading. Using a new large-scale database of naming responses, we first provided
      a precise estimate of the amount of reproducible variance that models should try
      to account for with such databases. Second, by using an item-level measure of
      delayed naming, we showed that it captures not only the variance usually
      explained by onset phonetic properties, but also an additional part of the
      variance related to output processes. Finally, by comparing the item means from
      this new database with the ones reported in a previous study, we found that the
      two sets of item response times were highly reliable (r = .94) when the variance
      related to onset phonetic properties and voice-key sensitivity was factored out.
      Overall, the present results provide new guidelines for testing computational
      models of word naming with item-level databases.

PMID- 23132608
TI  - Negative prospective memory: remembering not to perform an action.
AB  - Sometimes it is important to remember not to perform an action, such as
      remembering to stop taking seasonal allergy medicine when it is no longer needed.
      Mistakes in accomplishing this goal can involve prospective memory commission
      errors when individuals mistakenly perform a prospective response. In two
      experiments, we investigated the role of attentional resources in preventing
      prospective memory errors to cues that had been associated with a habitual
      prospective response. In Phase 1 of our experiments, participants performed a
      prospective memory task during which they either routinely responded to
      prospective memory cues or responded to these cues one time only. On a subsequent
      prospective memory task, the participants who had routinely responded to
      prospective memory cues were vulnerable to commission errors when their
      attentional resources were taxed. By contrast, dividing attention did not
      increase commission errors to cues that had not been routinely performed on an
      earlier task. These data indicate that attentional resources are needed to
      withhold making habitual prospective memory responses, and they suggest that
      inhibitory failures are a cause of these prospective memory errors. Finally, we
      suggest a broader definition of prospective memory that includes remembering to
      withhold performing actions.

PMID- 23132605
TI  - Augmented visual, auditory, haptic, and multimodal feedback in motor learning: a
      review.
AB  - It is generally accepted that augmented feedback, provided by a human expert or a
      technical display, effectively enhances motor learning. However, discussion of
      the way to most effectively provide augmented feedback has been controversial.
      Related studies have focused primarily on simple or artificial tasks enhanced by
      visual feedback. Recently, technical advances have made it possible also to
      investigate more complex, realistic motor tasks and to implement not only visual,
      but also auditory, haptic, or multimodal augmented feedback. The aim of this
      review is to address the potential of augmented unimodal and multimodal feedback
      in the framework of motor learning theories. The review addresses the reasons for
      the different impacts of feedback strategies within or between the visual,
      auditory, and haptic modalities and the challenges that need to be overcome to
      provide appropriate feedback in these modalities, either in isolation or in
      combination. Accordingly, the design criteria for successful visual, auditory,
      haptic, and multimodal feedback are elaborated.

PMID- 23132609
TI  - The European Heart Journal on the move: can scientific publishing be further
      improved?

PMID- 23132610
TI  - Risk assessment and therapy decision in patients at low risk for stroke: CHA2DS2
      VASc vs. CHADS2?

PMID- 23132611
TI  - Outcomes following radical cystectomy for micropapillary bladder cancer versus
      pure urothelial carcinoma: a matched cohort analysis.
AB  - PURPOSE: Micropapillary (MP) bladder cancer is a rare variant of urothelial
      carcinoma (UC) which has been associated with an aggressive natural history. We
      sought to report the outcomes of patients with MP bladder cancer treated with
      radical cystectomy (RC) and compare survival to patients with pure UC of the
      bladder. METHODS: We identified 73 patients with MP bladder cancer and 748
      patients with pure UC who underwent RC at our institution with median
      postoperative follow-up of 9.6 years. MP patients were stage-matched 1:2 to
      patients with pure UC. Survival was estimated using the Kaplan-Meier method and
      compared with the log-rank test. RESULTS: MP cancers were associated with a high
      rate of adverse pathologic features, as 48/73 patients (66 %) had pT3/4 tumors
      and 37 (50 %) had pN+ disease. Ten-year cancer-specific survival in MP patients
      was 31 %, compared with 53 % in the overall cohort with pure UC (p = 0.001). When
      patients with MP bladder cancer were then stage-matched to those with pure UC, no
      significant differences between the groups were noted with regard to 10-year
      local recurrence-free survival (62 vs. 69 %; p = 0.87), distant metastasis-free
      survival (44 vs. 56 %; p = 0.54), or cancer-specific survival (31 vs. 40 %; p =
      0.41). CONCLUSION: MP cancers are associated with a higher rate of locally
      advanced disease. However, when matched to patients with pure UC, patients with
      MP tumors did not have increased local/distant recurrence or adverse cancer
      specific survival following RC.

PMID- 23132612
TI  - Treatment for liver metastasis from renal cell carcinoma with computed-tomography
      guided high-dose-rate brachytherapy (CT-HDRBT): a case series.
AB  - PURPOSE: To retrospectively analyze the clinical outcome of patients with hepatic
      metastases from renal cell carcinoma who were treated with computed-tomography
      guided high-dose-rate brachytherapy (CT-HDRBT). METHODS: Ten patients (7 men and
      3 women; median age 72 +/- 7.9 years) with a total number of 16 hepatic
      metastases from histologically proven renal cell carcinoma were treated with CT
      HDRBT after discussing the case in an interdisciplinary tumor conference. All
      patients had underwent nephrectomy before CT-HDRBT. Three patients had
      extrahepatic manifestations (2 lung and 1 bone). Six patients had received
      immunotherapy or targeted therapy before CT-HDRBT. Follow-up included gadoxetic
      acid (Gd-EOB-DTPA) enhanced MRI two times within 6-8 weeks and after that every 3
      months after treatment to evaluate treatment efficacy. RESULTS: Mean follow-up
      time was 21.6 +/- 13.7 months. One patient developed local and systemic
      (pulmonary and osseous) progression after 10.8 months which was treated with
      targeted therapy and died 20.3 months after CT-HDRBT. None of the remaining nine
      patients developed local progression or died during the follow-up period. Five
      patients developed systemic progression (3 pulmonary, 1 osseous and 1 locally at
      the site of nephrectomy) after an average of 19.7 +/- 5.5 months. CONCLUSIONS: CT
      HDRBT is a viable alternative to hepatic resection of liver metastases from renal
      cell carcinoma in selected patients.

PMID- 23132613
TI  - Genetic association studies in pre-eclampsia: systematic meta-analyses and field
      synopsis.
AB  - BACKGROUND: Pre-eclampsia is thought to have a polygenic basis, but the
      identification of susceptibility genes and the quantification of associated risks
      have been elusive owing to lack of replication from published genetic association
      studies. OBJECTIVE: To perform a systematic review and meta-analysis of genetic
      association studies to evaluate the evidence for the associations of various
      candidate genes with pre-eclampsia. METHODS: For inclusion, studies had to
      involve unrelated subjects and examine the associations between pre-eclampsia
      (excluding publications without a measurement of proteinuria) and any candidate
      variant. Authors were contacted to obtain unpublished data when necessary. A meta
      analysis was conducted for all variants with three or more independent samples
      available. Summary odds ratios (ORs), 99% confidence intervals (CIs) and P-values
      were calculated using random effects models. RESULTS: Data from 192 genetic
      association studies met the selection criteria and were included in 25
      independent meta-analyses. There was some evidence of association for F5 rs6025
      (OR = 1.74; 99% CI 1.43-2.12), F2 rs1799963 (OR = 1.72; 99% CI 1.31-2.26), ACE
      rs4646994 (OR = 1.17; 99% CI 0.99-1.40), AGT rs699 (OR = 1.26; 99% CI 1.00-1.59)
      and AGTR1 rs5186 (OR = 1.22; 99% CI 0.96-1.56), but only the first two
      associations reached moderate epidemiological credibility. Possible bias
      resulting from small study size and poor reporting of individual studies were the
      most important factors affecting the reported associations. CONCLUSION: To date,
      candidate gene studies in pre-eclampsia have not robustly documented any
      associations with strong epidemiological credibility. Large-scale replication of
      the most promising associations, exhibited by two genetic variants, and
      incorporation of agnostic high-throughput data may improve our genetic knowledge
      base for this complex phenotype.

PMID- 23132614
TI  - Cohort profile: the Caerphilly health and social needs electronic cohort study (E
      CATALyST).
AB  - The Caerphilly Health and Social Needs study was established to inform and
      support collaborative multiagency working on reducing inequalities in health and
      to investigate neighbourhood influences on mental health. Initially, we collated
      a robust small-area multiagency dataset of contextual health determinants and
      outcomes from routine sources and sharing of data between the National Health
      Service and Caerphilly county borough council. These data were widely used in
      local joint planning to improve health and reduce health inequalities. Secondly,
      we carried out a baseline population questionnaire survey, collecting data from
      10 892 (60.6%) respondents aged 18-74 years on a wide range of socio-economic,
      lifestyle, health and housing factors and perceptions of the local neighbourhood,
      including access to services, social cohesion and neighbourhood quality. We
      carried out wave 2 of the survey after 7 years with responses from 4558 (50.2%)
      participants to the same range of questions. We developed the study into an
      electronic cohort, linking all 17 979 sampled participants aged 18-74 years to
      mortality and hospital admission records with 10-year follow-up and full
      recording of migration both within and out of the borough. Readers with an
      interest in collaborative use of the data should contact Professor David Fone,
      Principal Investigator.

PMID- 23132616
TI  - Influence of plant size on the ecophysiology of the epiphytic fern Asplenium
      auritum (Aspleniaceae) from Costa Rica.
AB  - PREMISE OF THE STUDY: A central goal of plant ecophysiological studies is to
      generate patterns of physiological behavior that are applicable to a species,
      which can be complicated when plant size is considered. Studies indicate that
      plant size can influence numerous ecophysiological parameters, especially in
      vascular epiphytes. The few studies that have included ferns in their analyses
      suggest that plant size is less important in ferns than angiosperms. This study
      investigates this apparent disparity by examining the relationship between plant
      size and an array of ecophysiological parameters in the epiphytic fern Asplenium
      auritum, especially the role of plant size in determining responses to water
      stress. METHODS: Plants were classified according to size and measured for a
      variety of functional traits, including maximum photosynthetic rate, stomatal
      conductance, water-use efficiency, stomatal density, chlorophyll content,
      chlorophyll a/b ratio, specific leaf area, whole plant drying rates, and
      desiccation tolerance. Results for all traits were compared across size classes
      to determine size-related differences. KEY RESULTS: Plant size significantly
      influenced most traits examined, most notably photosynthetic rate, stomatal
      density, stomatal conductance, whole plant drying rates, and recovery from
      desiccation. We report the first evidence of size-mediated shifts in desiccation
      tolerance in plants: small individuals tolerated water loss, whereas larger
      individuals avoided desiccation. CONCLUSIONS: Our findings indicate that size
      mediated ecophysiological shifts are more important than previously thought in
      ferns, particularly in regard to water relations. Desiccation tolerance may allow
      young fern sporophytes to establish in stressful environments and is subsequently
      lost in older individuals.

PMID- 23132615
TI  - The leaf-area shrinkage effect can bias paleoclimate and ecology research.
AB  - PREMISE OF THE STUDY: Leaf area is a key trait that links plant form, function,
      and environment. Measures of leaf area can be biased because leaf area is often
      estimated from dried or fossilized specimens that have shrunk by an unknown
      amount. We tested the common assumption that this shrinkage is negligible.
      METHODS: We measured shrinkage by comparing dry and fresh leaf area in 3401
      leaves of 380 temperate and tropical species and used phylogenetic and trait
      based approaches to determine predictors of this shrinkage. We also tested the
      effects of rehydration and simulated fossilization on shrinkage in four species.
      KEY RESULTS: We found that dried leaves shrink in area by an average of 22% and a
      maximum of 82%. Shrinkage in dried leaves can be predicted by multiple
      morphological traits with a standard deviation of 7.8%. We also found that mud
      burial, a proxy for compression fossilization, caused negligible shrinkage, and
      that rehydration, a potential treatment of dried herbarium specimens, eliminated
      shrinkage. CONCLUSIONS: Our findings indicate that the amount of shrinkage is
      driven by variation in leaf area, leaf thickness, evergreenness, and woodiness
      and can be reversed by rehydration. The amount of shrinkage may also be a useful
      trait related to ecologically and physiological differences in drought tolerance
      and plant life history.

PMID- 23132617
TI  - Germination failure is not a critical stage of reproductive isolation between
      three congeneric orchid species.
AB  - PREMISE OF THE STUDY: In food-deceptive orchid species, postmating reproductive
      barriers (fruit set and embryo mortality) have been shown to be more important
      for reproductive isolation than premating barriers (pollinator isolation).
      However, currently there is very little knowledge about whether germination
      failure acts as a reproductive barrier in hybridizing orchid species. METHODS: In
      this study, we investigated germination and protocorm development of pure and
      hybrid seeds of three species of the orchid genus Dactylorhiza. To test the
      hypothesis that germination failure contributed to total reproductive isolation,
      reproductive barriers based on germination were combined with already available
      data on early acting barriers (fruit set and embryo mortality) to calculate the
      relative and absolute contributions of these barriers to reproductive isolation.
      KEY RESULTS: Protocorms were formed in all crosses, indicating that both hybrid
      and pure seeds were able to germinate and grow into protocorms. Also, the number
      of protocorms per seed packet was not significantly different between hybrid and
      pure seeds. High fruit set, high seed viability, and substantial seed germination
      resulted in very low reproductive isolation (average RI = 0.05). In two of six
      interspecific crosses, hybrids performed even better than the intraspecific
      crosses. CONCLUSIONS: Very weak postmating reproductive barriers were observed
      between our study species and may explain the frequent occurrence of first
      generation hybrids in mixed Dactylorhiza populations. Germination failure, which
      is regarded as one of the most important bottlenecks in the orchid life cycle,
      was not important for reproductive isolation.

PMID- 23132618
TI  - Palynological composition of a Lower Cretaceous South American tropical sequence:
      climatic implications and diversity comparisons with other latitudes.
AB  - PREMISE OF THE STUDY: Reconstruction of floristic patterns during the early
      diversification of angiosperms is impeded by the scarce fossil record, especially
      in tropical latitudes. Here we collected quantitative palynological data from a
      stratigraphic sequence in tropical South America to provide floristic and
      climatic insights into such tropical environments during the Early Cretaceous.
      METHODS: We reconstructed the floristic composition of an Aptian-Albian tropical
      sequence from central Colombia using quantitative palynology (rarefied species
      richness and abundance) and used it to infer its predominant climatic conditions.
      Additionally, we compared our results with available quantitative data from three
      other sequences encompassing 70 floristic assemblages to determine latitudinal
      diversity patterns. KEY RESULTS: Abundance of humidity indicators was higher than
      that of aridity indicators (61% vs. 10%). Additionally, we found an angiosperm
      latitudinal diversity gradient (LDG) for the Aptian, but not for the Albian, and
      an inverted LDG of the overall diversity for the Albian. Angiosperm species
      turnover during the Albian, however, was higher in humid tropics. CONCLUSIONS:
      There were humid climates in northwestern South America during the Aptian-Albian
      interval contrary to the widespread aridity expected for the tropical belt. The
      Albian inverted overall LDG is produced by a faster increase in per-sample
      angiosperm and pteridophyte diversity in temperate latitudes. However, humid
      tropical sequences had higher rates of floristic turnover suggesting a higher
      degree of morphological variation than in temperate regions.

PMID- 23132620
TI  - Liver resection for hepatocellular carcinoma in patients without cirrhosis.
AB  - BACKGROUND: Data on liver resection for hepatocellular carcinoma (HCC) without
      cirrhosis are sparse. The present study was conducted to evaluate the indications
      and results of liver resection for HCC with regard to safety and efficacy.
      METHODS: Data for patients who had liver resection for HCC without cirrhosis
      between January 1996 and March 2011 were retrieved retrospectively using a
      prospective database containing information on all patients who underwent
      hepatectomy for HCC. Patient and tumour characteristics were analysed for
      influence on overall and disease-free survival to identify prognostic factors by
      univariable and multivariable analysis. RESULTS: The 1-, 3- and 5-year overall
      survival rates after resection with curative intent for HCC without cirrhosis
      were 84, 66 and 50 per cent respectively. Disease-free survival rates were 69, 53
      and 42 per cent respectively. The 90-day mortality rate was 4.5 per cent (5 of
      110 patients). Surgical radicality and growth pattern of the tumour were
      independent prognostic factors for overall survival. Disease-free survival after
      resection with curative intent was independently affected by growth pattern and
      by the number and size of tumour nodules. CONCLUSION: Liver resection for HCC
      without cirrhosis carries a low perioperative risk and excellent long-term
      outcome if radical resection is achieved.

PMID- 23132621
TI  - Correlates of mothers' perception of their communities' social capital: a
      community-based study.
AB  - Psychosocial issues have been recognized as important factors in children's
      health for decades. This study documents the relation among several important
      psychosocial variables (e.g., mothers' depressive symptoms) and a new instrument
      that assesses parents' perception of their communities' social capital. Mothers
      were recruited from their children's primary care (PC) pediatricians' offices
      within the Southwestern Ohio Ambulatory Research Network or from a children's
      hospital developmental clinic (DC). Mothers completed a questionnaire that
      included the Social Capital Scale (SCS), Children with Special Health Care Needs
      Screener (CSHCNS), Pediatric Quality of Life Inventory, Maternal Social Support
      Index and the Center for Epidemiologic Studies Depression Scale (CES-D). Mothers
      were sorted into three subgroups based on site of recruitment (PC or DC) and
      results of the CSHCNS. The sample (N = 620) was also sorted into terciles based
      on SCS scores. Mean SCS was about 73 for each of the three subgroups. Compared to
      mothers in the highest SCS tercile, mothers in the lowest SCS tercile reported
      lower education, lower income and higher CES-D median scores. The SCS subscale
      "sense of belonging" had an inverse correlation with CES-D scores (r = -.248, p <
      0.001). Mothers from primary care and sub-specialty clinics had similar
      perceptions about their communities' social capital. Compared to mothers in the
      highest one third of SCS scores, mothers in the lowest one third were more likely
      to report less education and income as well as more depressive symptoms. A
      decreased sense of belonging in their communities was also correlated with more
      depressive symptoms. The SCS is a new useful tool for investigators and
      clinicians who work with children and their families. 

PMID- 23132623
TI  - Zirconocene dichloride catalyzed hydrodefluorination of C(sp 2)-F bonds.
AB  - A two-metal job: Four-coordinate aluminum dihydrides such as 1 are reported as
      terminal reductants for the selective title reaction. The heterobimetallic
      complex 2 has been isolated and shown to be catalytically competent.

PMID- 23132624
TI  - Clinical evidence of parietal cortex dysfunction and correlation with extent of
      allodynia in CRPS type 1.
AB  - BACKGROUND: Unusual symptoms such as digit misidentification and neglect-like
      phenomena have been reported in complex regional pain syndrome (CRPS), which we
      hypothesized could be explained by parietal lobe dysfunction. METHODS: Twenty-two
      patients with chronic CRPS attending an in-patient rehabilitation programme
      underwent standard neurological examination followed by clinical assessment of
      parietal lobe function and detailed sensory testing. RESULTS: Fifteen (68%)
      patients had evidence of parietal lobe dysfunction. Six (27%) subjects failed six
      or more test categories and demonstrated new clinical signs consistent with their
      parietal testing impairments, which were impacting significantly on activities of
      daily living. A higher incidence was noted in subjects with >1 limb involvement,
      CRPS affecting the dominant side and in left-handed subjects. Eighteen patients
      (82%) had mechanical allodynia covering 3-57.5% of the body surface area.
      Allochiria (unilateral tactile stimulation perceived only in the analogous
      location on the opposite limb), sensory extinction (concurrent bilateral tactile
      stimulation perceived only in one limb), referred sensations (unilateral tactile
      stimulation perceived concurrently in another discrete body area) and dysynchiria
      (unilateral non-noxious tactile stimulation perceived bilaterally as noxious)
      were present in some patients. Greater extent of body surface allodynia was
      correlated with worse parietal function (Spearman's rho = -0.674, p = 0.001).
      CONCLUSION: In patients with chronic CRPS, detailed clinical examination may
      reveal parietal dysfunction, with severity relating to the extent of allodynia.

PMID- 23132625
TI  - Determination of time to onset and rate of action of insulin products: importance
      and new approaches.
AB  - One important aspect of insulin drug development is to ascertain that short
      acting insulins mimic the normal mealtime insulin release in healthy subjects.
      Therefore, it is important to identify metrics that allow identification of
      unique characteristics of insulin products based on pharmacokinetic (PK) (time
      concentration) or glucodynamic (time course of action) profiles. Current
      development programs use metrics such as "onset of action" to characterize
      insulin products, in addition to peak and area under the curve parameters for PK
      and glucodynamic profiles. However, in current practice, onset of action
      parameter is often interchangeably used with rate of action for insulin products,
      which points to existence of confusion about their definitions and methods of
      determination. In this paper, we discuss these two parameters with an underlying
      objective to prompt discussion on development of a quantitative standard for
      insulin products based on the onset and/or rate of action. This paper presents
      euglycemic clamp and meal challenge study data using a hypothetical insulin
      product and attempts to clear confusion by emphasizing on the distinct properties
      of these parameters.

PMID- 23132626
TI  - Obturator hernia-an uncommon cause of small bowel obstruction.

PMID- 23132627
TI  - Preoperative chemotherapy does not adversely affect pancreatic structure and
      short-term outcome after pancreatectomy.
AB  - BACKGROUND: Preoperative chemotherapy (PCHT) has recently been proposed also in
      patients with resectable pancreatic adenocarcinoma. Few data are currently
      available on the impact of PCHT on short-term postoperative outcome after
      pancreatic resection. The objective of this study is to assess the impact of PCHT
      on pancreatic structure and short-term outcome after surgical resection. METHODS:
      Fifty consecutive patients successfully underwent resection after PCHT. Each
      patient was matched with two control patients with pancreatic adenocarcinoma
      selected from our prospective electronic database. Match criteria were age (+/-3
      years), gender, American Society of Anesthesiologist score, type of resection,
      pancreatic duct diameter (+/-1 mm), and tumor size (+/-5 mm). Primary endpoint
      was morbidity rate. Secondary endpoints were pancreatic parenchymal structure,
      mortality rate, and length of hospital stay (LOS). RESULTS: Both degree of
      fibrosis and fatty infiltration of the pancreas were similar in the two groups.
      Overall morbidity rate was 48.0 % in the PCHT group vs. 54.0 % in the control
      group (p = 0.37). Pancreatic fistula rate was 18.0 % in the PCHT group vs. 25.0 %
      in the control group (p = 0.41). Mortality was 4.0 % in the PCHT group vs. 2.0 %
      in the control group (p = 0.60). Mean LOS (days) was 12.7 in the PCHT group vs.
      12.4 in the control group (p = 0.74). There was no difference in resection margin
      status, while the rate of patients without nodal involvement was higher in the
      PCHT group (46.0 vs. 23.0 %, p = 0.004). CONCLUSION: PCHT did not induce
      significant structural changes in pancreatic parenchyma and did not adversely
      affect short-term outcome after surgery.

PMID- 23132629
TI  - Unambiguous structure elucidation of heterocyclic products from condensation
      cyclisation reactions of enaminones by 2D INADEQUATE and 15N NMR.
AB  - The reaction of enaminones with 3-amino-2-cyanopent-2-enedinitrile can lead to an
      array of 12 possible products, depending on the reaction pathway and
      tautomerization. The use of 2D INADEQUATE and (15)N NMR for the unambiguous
      structure elucidation of the reaction products is discussed in this manuscript.

PMID- 23132628
TI  - The management of acute cholecystitis in chronic hemodialysis patients:
      percutaneous cholecystostomy versus cholecystectomy.
AB  - INTRODUCTION: Treatment of acute cholecystitis in chronic hemodialysis (HD)
      patients still remains controversial. Because of underlying disease that can
      influence surgical results, less invasive alternative managements have been tried
      over the last decades. The goal of this study was to analyze the results of
      cholecystectomy versus percutaneous cholecystostomy for acute cholecystitis (AC)
      in chronic HD patients. METHODS: All patients with end-stage renal disease who
      were treated for AC were identified retrospectively from our medical records.
      Between July 2007 and September 2011, 47 patients were treated for AC while they
      were on chronic HD. The records of these patients were reviewed for documented AC
      and its treatment. RESULTS: Of the 47 HD patients, 26 (55.3 %) underwent
      cholecystectomy (CC), while 21 (44. 7 %) had a percutaneous cholecystostomy (PC)
      for AC as an initial treatment. The mean length of follow-up was 20.4 +/- 16
      months in PC and 18 +/- 15 months in CC patients. The success rate was higher in
      CC patients compared to PC patients (92. 3 versus 66.7 %, p = 0.0698). Eleven
      (52. 4 %) patients who had PC subsequently underwent CC; six open CC and five
      delayed laparoscopic CC were performed. Of the 26 patients who underwent CC, 18
      were performed emergently due to the persistence of AC-related symptoms and
      gangrenous and perforated gallbladders. Eight were initially treated
      conservatively and then underwent elective cholecystectomy at an interval of 32
      +/- 24 (range = 14-59) days following initial treatment. In emergent CC, 10 (55.6
      %) were completed laparoscopically, three were open, and five (33.3 %) had
      conversions. In elective CC patients, two were conversions, but the remainder (75
      %) had laparoscopic CC. Readmission rates were higher in the PC group (33.3
      versus 12.5 %, p = 0.1732). Although AC-related mortality was higher in PC
      patients, there was no statistically significant difference in the patient
      survival rate between the two groups (Kaplan-Meier analysis, Fig. 1, 19 versus
      7.7 %; p = 0.4035), and the overall mortality rate was higher in the PC group
      (33.7 versus 15.7 %, p = 0.2737). CONCLUSION: This study confirms that the safety
      and effectiveness of CC has a higher success rate and lower morbidity and
      mortality rate compared with percutaneous cholecystostomy for acute cholecystitis
      in chronic HD patients.

PMID- 23132630
TI  - Growth and weight status of rural Texas school youth.
AB  - CONTEXT: Evidence indicates higher prevalence of obesity in rural American youth.
      The present study evaluates the growth status and estimates the prevalence of
      overweight and obesity among rural school children in Texas. METHODS: Heights and
      weights were measured in a sample of 1,084 school youth (545 males, 539 females)
      5-19 years of age, in rural north central Texas in 2010. body mass index (BMI)
      was calculated. Growth status was plotted relative to US reference data. Weight
      status (underweight/thin, overweight, and obesity) was classified relative to age
      and sex-specific Centers for Disease Control (CDC) and International Obesity
      Task Force (IOTF) criteria. Concordance of classifications was evaluated.
      RESULTS: Mean heights of the rural children approximated reference medians, while
      median weights exceeded reference medians and approximated 75th percentiles with
      increasing age. Median BMIs of boys and girls were below the 75th percentiles
      except among late adolescent girls. Prevalence of underweight/thinness was low
      (<4%). Overweight approximated 20% among boys 6-11 years and 16% among boys 12-19
      years with CDC criteria; the opposite was apparent for obesity, 6-11 years, 16%,
      and 12-19 years, 20%. Approximately, equal percentages of boys in both age groups
      were classified overweight (~21-22%) with IOTF criteria, but almost twice as many
      older (15%) than younger (8%) boys were classified obese. Overweight was less
      prevalent (~5%) but obesity more prevalent (~5%) with CDC compared to IOTF
      criteria, but both were less prevalent among younger than older girls.
      CONCLUSION: Prevalence of overweight and obesity among rural Texas school youth
      was comparable to national estimates for 2007-2008. The results highlight a need
      for programs aimed at preventing unhealthy weight gain and/or weight reduction
      given the tendency of obesity to track from childhood into adulthood and
      potentially negative health consequences of obesity. Am. J. Hum. Biol., 2013. (c)
      2012 Wiley Periodicals, Inc.

PMID- 23132631
TI  - Angelica keiskei ameliorates scopolamine-induced memory impairments in mice.
AB  - Memory impairment is the most common symptom in patients with Alzheimer's disease
      (AD). Angelica keiskei (AK) has traditionally been used as a diuretic, laxative,
      analeptic and galactagogue. However, the anti-amnesic effects of AK and its
      molecular mechanisms have yet to be clearly elucidated. The aim of the present
      study is to evaluate the effects of AK on scopolamine-induced memory impairments
      in mice. The regulatory effect of AK on memory impairment was investigated using
      passive avoidance, Y-maze and the Morris water maze tasks. Acetylcholinesterase
      (AChE) activity assay was performed to investigate the cholinergic antagonistic
      effect of AK in the hippocampus. The effect of AK on phosphorylation of cAMP
      response element-binding protein (CREB) and expression of brain-derived
      neurotrophic factor (BDNF) were evaluated by Western blot assays and
      immunohistochemistry. The findings showed that AK significantly attenuated
      scopolamine-induced cognitive impairment in mice. Increase of AChE activity
      caused by scopolamine was significantly attenuated by AK. Additionally, AK
      significantly recovered the phosphorylation of CREB and expression of BDNF
      reduced by scopolamine in the hippocampus. Taken together, these results provide
      experimental evidence that AK might be a useful agent in preventing deficit of
      learning and memory caused by AD and aging.

PMID- 23132632
TI  - Synthesis, crystal structure, and physical property of sterically unprotected
      thiophene/phenylene co-oligomer radical cations: a conductive pi-pi bonded
      supermolecular meso-helix.
AB  - Sterically unprotected thiophene/phenylene co-oligomer radical cation salts
      BPnT(.+) [Al(OR(F))(4)](-) (OR(F)=OC(CF(3))(3), n=1-3) have been successfully
      synthesized. These newly synthesized salts have been characterized by UV/Vis-NIR
      absorption and EPR spectroscopy, and single-crystal X-ray diffraction analysis.
      Their conductivity increases with chain length. The formed meso-helical stacking
      by cross-overlapping radical cations of BP2T(.+) is distinct from previously
      reported face-to-face overlaps of sterically protected (co-)oligomer radical
      cations.

PMID- 23132633
TI  - Relationship between the degree of property damage and changes in red blood
      cells, hematocrit, and hemoglobin among victims of the Noto Peninsula Earthquake.
AB  - OBJECTIVES: The aim of this study was to assess the impact of the Noto Peninsula
      Earthquake on various hematologic parameters. We studied the relationships
      between the degree of property damage and changes in red blood cells (RBCs),
      hemoglobin (Hb), and hematocrit (Ht) among residents before and after the March
      2007 Noto Peninsula Earthquake. METHODS: A total of 5,563 residents of Wajima
      City who were not receiving oral treatment for anemia and who had received basic
      health screenings for fiscal years (FYs) 2006 and 2007, before and after the
      earthquake. We analyzed changes in their RBCs, Hb, and Ht levels by gender, age,
      body mass index (BMI), level of property damage, and evaluation standards.
      RESULTS: RBCs, Hb, and Ht for FY2007 showed a trend of decreasing values compared
      to FY2006 in both male and female subjects. RBCs and Hb significantly decreased
      in females aged between 65 and 74 years who experienced total property damage,
      and Ht significantly increased for those younger than 65 years who experienced
      the same level of damage. In addition, significant differences by degree of
      property damage and FY2007/FY2006 ratio were seen only among subjects with a BMI
      ratio <1. Furthermore, we found a significant relationship between reduction of
      RBCs or Hb and increasing age in females; however, no significant relationship to
      property damage was found. No significant relationships were found for males.
      CONCLUSIONS: A significant association between property damage and changes in
      RBCs, Hb, and Ht was not found in this population of residents who experienced
      the Noto Peninsula Earthquake.

PMID- 23132635
TI  - Returns on lifetime investments in children in Egypt.
AB  - Parental expectations about the companionship and assistance they will receive in
      later life from their children are key considerations in family formation
      decisions. We explore patterns of parents' investment and the support and contact
      they receive from adult children in Egypt, where fertility is falling and sources
      of support at all life stages are in flux. Using data from a survey of older
      adults in Ismailia governorate, we consider parents' past investments in
      childbearing, child survival, and children's education and marriage, as well as
      recent assistance to adult children via housing, care for grandchildren, gifts,
      and money. The returns from children considered include economic assistance,
      instrumental support, and visits. Most parental investments are associated with
      frequent visits from children. The assistance children provide to parents is
      gendered: sons tend to provide economic transfers, whereas daughters tend to
      provide instrumental help. A greater number of surviving children is most
      strongly associated with parents' receipt of multiple types of later-life
      returns. Investments in children's education and marriage are not associated with
      assistance, but recent assistance to children-especially economic transfers and
      provision of housing-is associated with receiving instrumental assistance from
      adult children.

PMID- 23132636
TI  - Chemoprevention of intestinal adenomatous polyposis by acetyl-11-keto-beta
      boswellic acid in APC(Min/+) mice.
AB  - Acetyl-11-keto-beta-boswellic acid (AKBA) is a derivative of boswellic acid,
      which is an active component of the gum resin of Boswellia serrata. AKBA has been
      used as an adjuvant medication for treatment of inflammatory diseases. In this
      study, we aimed to evaluate the efficacy of AKBA as a chemopreventive agent
      against intestinal adenomatous polyposis in the adenomatous polyposis coli
      multiple intestinal neoplasia (APC(Min/+) ) mouse model. APC(Min/+) mice were
      administered AKBA by p.o. gavage for 8 consecutive weeks. The mice were
      sacrificed and the number, size and histopathology of intestinal polyps were
      examined by light microscopy. AKBA decreased polyp numbers by 48.9% in the small
      intestine and 60.4% in the colon. An even greater AKBA effect was observed in
      preventing the malignant progression of these polyps. The number of large (>3 cm)
      colonic polyposis was reduced by 77.8%. Histopathologic analysis demonstrated a
      significant reduction in the number of dysplastic cells and in the degree of
      dysplasia in each polyp after AKBA treatment. There was no evidence of high grade
      dysplasia or intramucosal carcinoma in any of the polyps examined within the
      treated group. More interestingly, interdigitated normal appearing intestinal
      villi were observed in the polyps of the treated group. During the course of the
      study, AKBA was well tolerated by the mice with no obvious signs of toxicity.
      Results from immunohistochemical staining, Western blotting and enzyme-linked
      immunosorbent assay indicated that the chemopreventive effect of AKBA was
      attributed to a collection of activities including antiproliferation, apoptosis
      induction, antiangiogenesis and anti-inflammation. AKBA was found to exert its
      chemopreventive action through the inhibition of the Wnt/beta-catenin and NF
      kappaB/cyclooxygenase-2 signaling pathways. Our findings suggest that AKBA could
      be a promising regimen in chemoprevention against intestinal tumorigenesis.

PMID- 23132637
TI  - Venous aneurysms of saphena magna: is this really a rare disease? : Comment to: A
      challenging hernia: primary venous aneurysm of the proximal saphenous vein.

PMID- 23132638
TI  - Anaesthetic preference and outcomes for elective inguinal hernia repair: a
      comparative analysis of public and private hospitals.
AB  - PURPOSE: There is paucity of data regarding patient selection criteria,
      anaesthetic preferences and outcomes of elective inguinal hernia repair in public
      and private sector in the UK. This study aimed to compare such outcomes. METHODS:
      Five hundred and fifty-five consecutive inguinal hernia repairs performed by one
      consultant surgeon in public and private sector were reviewed from a
      prospectively maintained database. The patient demographics, anaesthetic choice,
      day case rates and early and long-term morbidity were analysed. RESULTS: The
      median age of the study group was 59 years (range 16-96 years) with a male/female
      ratio of 21:1. A total of 436 (78 %) patients underwent surgery in the public
      sector and 119 (22 %) patients in the private sector. The patients undergoing
      surgery in the private sector were younger compared to public sector (55 vs. 60
      years, p = 0.03). The number of patients with ASA grades III and IV was higher in
      public sector (28.6 %) compared to private sector (p = 0.0001). General
      anaesthesia was the preferred anaesthetic technique in the private sector (52 %)
      and local anaesthesia in the public sector (66 %) (p = 0.0002). The day case
      rates were higher than in the private sector compared to public sector (78 vs.
      66.5 %, p = 0.01). No significant difference was noted in the incidence of post
      operative complications, recurrence, groin pain and satisfaction rate between the
      two groups. CONCLUSION: Patients undergoing surgery in the private sector are
      younger, healthier, prefer general anaesthesia and have higher day case rates
      compared to public sector. The short- and long-term outcomes are similar between
      public and private sectors.

PMID- 23132639
TI  - Comparing laparoscopic and open inguinal hernia repair in octogenarians.
AB  - PURPOSE: To compare outcomes of laparoscopic and open inguinal hernia repair in
      elderly patients. METHODS: We retrospectively reviewed patients >=80 years old
      undergoing laparoscopic or open inguinal hernia repair from October 2006 to July
      2009 at our medical center. Descriptive statistics were calculated, and outcomes
      were compared using Fisher's exact test, Wilcoxon rank-sum test, and Student's t
      test; a p value <0.05 was considered significant. RESULTS: Open inguinal hernia
      repairs were performed in 58 patients, and laparoscopic repairs in 23 patients.
      There was no significant difference in average age (81 vs. 83 years, p = 0.09) or
      gender (91 % male vs. 74 % male, p = 0.1) for the laparoscopic versus open
      groups. Resident involvement (55 vs. 26 %, p = 0.02) was more common in the open
      group, and there was no difference in number of cases done for incarcerated
      hernias (17 vs. 13 %, p = 0.8) in the open versus laparoscopic groups. We
      observed a significant difference in hernia laterality and anesthesia type, with
      significantly more bilateral hernias (48 vs. 2 %, p <= 0.001) and more general
      anesthesia (100 vs. 31 %, p <= 0.001) in the laparoscopic compared with the open
      group. There were no significant differences in ASA score (p = 0.1), operating
      room time (p = 0.6), urine output (p = 0.1), morbidity (p = 1), or mortality
      unrelated to the hernia surgery (13 vs. 22 %, p = 0.5) between the laparoscopic
      and open groups. At an average follow-up of 31 months (laparoscopic) and 19
      months (open), only one recurrence occurred (open group). CONCLUSIONS: Despite
      subtle differences between the laparoscopic and open approaches to inguinal
      hernia repairs in octogenarians, both procedures are safe with similar outcomes.

PMID- 23132640
TI  - A study of postural changes after abdominal rectus plication abdominoplasty.
AB  - PURPOSE: Factors such as body masses and humour are known to influence human
      posture. Abdominoplasty, which causes a sudden change in body masses,
      significantly improves body image and self-esteem. The aim of this study was to
      assess postural changes after abdominoplasty by studding the position and
      orientation through space of the body and the centre of pressure. METHODS:
      Patients affected by excess abdominal skin and/or significant abdominal muscular
      anterior wall laxity due to undergo an abdominoplasty were enrolled. Posture was
      evaluated both before and for 1 year after surgery by quantifying the centres of
      mass, using the FastrakTM system, and the centre of pressure, using stabilometry.
      The Wilcoxon signed-rank sum test was used to compare changes. RESULTS: Forty-six
      patients were enrolled. A retro-positioning of the pelvis with a compensatory
      advancement of the head and shoulders, confirmed by the baropodometric analysis,
      was evident in the early post-operative period. The biomechanical system
      subsequently stabilized, achieving a state of equilibrium 1 year after surgery.
      CONCLUSIONS: We believe that the change in posture following abdominoplasty is a
      consequence of both surgery (changes in body masses) and psychological factors
      that influence posture. Indeed, redundant abdominal skin and abdominal muscular
      anterior wall weakness are often associated with kyphosis since patients try to
      hide what they consider to be a source of embarrassment. The discovery of a new
      body image eliminates dissatisfaction, reduces anxiety and increases self-esteem,
      which provide psychological and physical benefits that improve the quality of
      life.

PMID- 23132641
TI  - Change in flatfoot of preschool-aged children: a 1-year follow-up study.
AB  - The main purpose of this study is to investigate the changes in the signs of
      flatfoot of preschool-aged children in a 1-year follow-up study. This study
      performed follow-up on a total of 580 preschool-aged children (boys, 297
      children; girls, 283 children) with a median age of 54 (range 36-71 months), and
      the average follow-up period was 11.8 months. This study used the Chippaux-Smirak
      index (CSI) of footprint as the assessment tool, and CSI > 62.70 % was used as
      the standard for determining whether preschool-aged children suffered from
      flatfoot. The results showed that the signs of flatfoot of preschool-aged
      children improved with increasing age. At the 1-year follow-up, the average CSI
      was 5.1 % lower, and the proportion of children with flatfoot was 14 % lower. The
      follow-up on the change in the signs of flatfoot showed that 37.6 % of the
      children originally with flatfoot had improved to normal, verifying that flatfoot
      indeed improves with increasing age. However, the results also showed that 9.9 %
      of the children who originally had normal feet had developed flatfoot with
      increasing age, which deserves subsequent investigation. The results of the
      follow-up also showed that children who were relatively younger, male, obese, and
      experiencing excessive joint laxity were more likely to experience the signs of
      flatfoot. CONCLUSION: The 1-year follow-up found that some preschool-aged
      children with flatfoot may develop normal feet, while children with normal feet
      may begin to experience the signs. Relevant factors affecting flatfoot in
      preschool-aged children continue to require further clarification.

PMID- 23132642
TI  - Effect of non-human neutral and acidic oligosaccharides on allergic and
      infectious diseases in preterm infants.
AB  - Short-term supplementation of non-human neutral and acidic oligosaccharides
      during the first postnatal weeks may enhance the maturation of the immune
      response in preterm infants and may lead to less allergic and infectious diseases
      during the first year of life. In a randomized controlled trial, 113 preterm
      infants (gestational age <32 weeks and/or birth weight <1500 g) were allocated to
      receive enteral neutral and acidic oligosaccharide supplementation or placebo
      between days 3 and 30 of life. The median age at follow-up was not different in
      both groups: 12 months corrected age (interquartile range [IQR], 11-15) in the
      prebiotic mixture group and 12 months corrected age in the placebo group (IQR, 10
      19), respectively. In addition, baseline patient, maternal, and environmental
      characteristics were not different between the prebiotic mixture (n = 48) and
      placebo (n = 46) group. Incidence of allergic and infectious diseases was
      assessed by validated questionnaires. In total, 94/98 (96 %) of the eligible,
      surviving infants participated in this follow-up study. The incidence of atopic
      dermatitis (odds ratio [OR], 0.80; 95 % confidence interval [CI], 0.24-2.67),
      bronchial hyper-reactivity (OR, 1.04; 95 % CI, 0.38-2.87) and infections of the
      upper respiratory (OR, 0.95; 95 % CI, 0.37-2.44), lower respiratory (OR, 1.03; 95
      % CI, 0.37-2.88), and gastrointestinal (OR, 1.77; 95 % CI, 0.55-5.73) tract was
      not different between the groups. Adjustment for potential confounding factors
      did not change the results of the primary analysis. CONCLUSION: Short-term
      enteral supplementation of non-human neutral and acidic oligosaccharides during
      the neonatal period in preterm infants does not decrease the incidence of
      allergic and infectious diseases during the first year of life.

PMID- 23132644
TI  - Application of near-infrared dyes for tumor imaging, photothermal, and
      photodynamic therapies.
AB  - Near-infrared (NIR) dyes, small organic molecules that function in the NIR
      region, have received increasing attention in recent years as diagnostic and
      therapeutic agents in the field of tumor research. They have been demonstrated
      great successes in imaging and treating tumors both in vitro and in vivo. And
      their different applications in clinical practices have made rapid gains. This
      review primarily focuses on the progress of the application of NIR dyes in tumor
      imaging and therapy. In particular, advances in the use of different NIR dyes in
      tumor-specific imaging, photothermal, and photodynamic therapies are discussed.
      Limitations and prospects associated with NIR dyes in diagnostic and therapeutic
      application are also reviewed.

PMID- 23132643
TI  - Experimental myalgia induced by repeated infusion of acidic saline into the human
      masseter muscle does not cause the release of algesic substances.
AB  - BACKGROUND: Animal studies have shown that two repeated intramuscular injections
      of acidic saline induce mechanical allodynia that lasts for 4 weeks with spread
      to the contralateral side. In this study, we tested the hypothesis that two
      repeated intramuscular infusions of acidic saline into the human masseter muscle
      is associated with pain, mechanical allodynia and release of algesic substances.
      Eighteen healthy volunteers participated. On day 1, 2.5 mL of acidic saline (pH
      3.3) was infused into one of the masseter muscles and isotonic saline (pH 6.0)
      into the other (randomized and single-blind). Two days later, intramuscular
      microdialysis was performed to sample serotonin, glutamate, pyruvate, lactate and
      glucose, during which the saline infusions were repeated. Pain and pressure pain
      thresholds (PPTs) were recorded before and after infusions on both days. RESULTS:
      Pain intensity induced by the infusions was higher after acidic than that after
      isotonic saline (p < 0.05). PPTs were decreased on both sides after microdialysis
      compared with baseline day 1 (p's < 0.05), but there were no differences in PPTs
      between sides at any time point. The levels of serotonin, glutamate, pyruvate,
      lactate or glucose did not change significantly during microdialysis. CONCLUSION:
      Infusion of acidic saline caused low levels of muscle pain, but no mechanical
      allodynia and no increased release of algesic substances. The value of this model
      appears modest, but future studies could be performed with larger sample size and
      higher flow rate before definite conclusions about the validity of the model for
      craniofacial myalgia can be drawn.

PMID- 23132645
TI  - First birth interval, an indicator of energetic status, is a predictor of
      lifetime reproductive strategy.
AB  - OBJECTIVES: Women should differ in their reproductive strategies according to
      their nutritional status. We tested a hypothesis that women who have a good
      nutritional status early in life, as indicated by a shorter waiting time to the
      first birth (first birth interval, FBI), are able to afford higher costs of
      reproduction than women who have worse nutritional condition. METHODS: We
      collected data on 377 women who got married between the years 1782 and 1882 in a
      natural fertility population in rural Poland. The study group was divided into
      tertiles based on the length of FBI. RESULTS: Women with the shortest FBI had a
      higher number of children (P = 0.005), higher number of sons (P = 0.01), and
      shorter mean interbirth intervals (P = 0.06). Women who had ever given birth to
      twins had shorter FBI than women of singletons (20.1 and 26.1 months,
      respectively; P = 0.049). Furthermore, women with a shorter FBI, despite having
      higher costs of reproduction, did not have a different lifespan than women with a
      longer FBI. CONCLUSIONS: Our results suggest that women who were in better
      energetic condition (shorter length of FBI), achieved higher reproductive success
      without reduction in lifespan. FBI reflects interindividual variation, which may
      result from variation in nutritional status early in life and thus may be a good
      predictor of subsequent reproductive strategy. We propose to use FBI as an
      indicator of women's nutritional status in studies of historical populations,
      especially when information about social status is not available.

PMID- 23132646
TI  - Gain control in the sonar of odontocetes.
AB  - The sonar of odontocetes processes echo-signals within a wide range of echo
      levels. The level of echoes varies widely by tens of decibels depending on the
      level of the emitted sonar pulse, the target strength, the distance to the
      target, and the sound absorption by the water media. The auditory system of
      odontocetes must be capable of effective perception, analysis, and discrimination
      of echo-signals within all this variability. The sonar of odontocetes has several
      mechanisms to compensate for the echo-level variation (gain control). To date,
      several mechanisms of the biosonar gain control have been revealed in
      odontocetes: (1) adjustment of emitted sonar pulse levels (the longer the
      distance to the target, the higher the level of the emitted pulse), (2) short
      term variation of hearing sensitivity based on forward masking of the echo by the
      preceding self-heard emitted pulse and subsequent release from the masking, and
      (3) active long-term control of hearing sensitivity. Recent investigations with
      the use of the auditory evoked-potential technique have demonstrated that these
      mechanisms effectively minimize the variation of the response to the echo when
      either the emitted sonar pulse level, or the target distance, or both vary within
      a wide range. A short review of these data is presented herein.

PMID- 23132647
TI  - Reference ranges for vertebral heights and prevalence of asymptomatic
      (undiagnosed) vertebral fracture in Vietnamese men and women.
AB  - Based on quantitative measurements of vertebral heights, the prevalence of
      undiagnosed vertebral fracture in Vietnamese men and women aged 50 years and
      older was 23 and 26 %, respectively. BACKGROUND: The present study sought to
      develop reference ranges for vertebral heights and to determine the prevalence of
      asymptomatic vertebral fracture in Vietnamese men and women. METHODS: The study
      included 312 men and 657 women aged over 18 who were randomly selected from the
      community. The ImageJ software program was used to measure anterior height
      (H(a)), middle height (H(m)), and posterior height (H(p)) for each vertebra (T4
      to T12 and L1 to L5). Four vertebral ratios were determined: H(a)/H(p),
      H(m)/H(p), H(p)/H(p + 1), and H(p)/H(p - 1). Reference ranges for the ratios were
      then developed by the method of Winsorized mean. Vertebral fracture was diagnosed
      as a ratio lower than three standard deviations from the normal mean. RESULTS:
      For any given vertebra, H(a), H(m), and H(p) in men were higher than in women. In
      both sexes, H(a) and H(m) increased in a stepwise fashion from T4 to L3 and then
      gradually reduced in L4-L5. Vertebral heights for T4-T9 tended to decrease, while
      vertebral height for T10-L5 tended to increase with advancing age. Among those
      aged over 50 years, the prevalence of vertebral fracture in men was 23.3 % (95 %
      confidence interval (CI) 16.8-31.3 %) which was lower than that in women (26.5 %;
      95 % CI 22.4-31.1 %). The prevalence increased with advancing age, such that from
      the age of over 70, 41 % of men and 42 % women had at least one vertebral
      fracture. CONCLUSION: One fourth of Vietnamese men and women aged 50 years and
      older have a symptomatic vertebral fracture. This prevalence is equivalent to
      that in Caucasian populations.

PMID- 23132648
TI  - Preparation of chiral alpha-substituted alaninates through an efficient
      diastereoselective synthesis of trisubstituted allylic alcohols.

PMID- 23132649
TI  - Preparation of bifunctional mesoporous silica nanoparticles by orthogonal click
      reactions and their application in cooperative catalysis.
AB  - The synthesis of bifunctional mesoporous silica nanoparticles is described. Two
      chemically orthogonal functionalities are incorporated into mesoporous silica by
      co-condensation of tetraethoxysilane with two orthogonally functionalized
      triethoxyalkylsilanes. Post-functionalization is achieved by orthogonal surface
      chemistry. A thiol-ene reaction, Cu-catalyzed 1,3-dipolar alkyne/azide
      cycloaddition, and a radical nitroxide exchange reaction are used as orthogonal
      processes to install two functionalities at the surface that differ in
      reactivity. Preparation of mesoporous silica nanoparticles bearing acidic and
      basic sites by this approach is discussed. Particles are analyzed by solid state
      NMR spectroscopy, elemental analysis, infrared-spectroscopy, and scanning
      electron microscopy. As a first application, these particles are successfully
      used as cooperative catalysts in the Henry reaction.

PMID- 23132650
TI  - Organocatalytic, highly enantioselective vinylogous Mukaiyama-Michael reaction of
      acyclic dienol silyl ethers.
AB  - Now also acyclic: The first catalytic, enantioselective, vinylogous Michael
      reaction of linear, acyclic dienol silyl ethers was achieved. The reaction, based
      upon the principle of iminium ion catalysis, delivered 1,7-dioxo compounds in one
      step with good yields, complete regio-, and excellent enantioselectivity. gamma
      Substituted dienol silyl ethers furnished products with two new stereogenic
      centers with good diastereoselectivity. Ms = mesityl, PNBA = para-nitrobenzoic
      acid.

PMID- 23132651
TI  - Ammonia upregulates kynurenine aminotransferase II mRNA expression in rat brain:
      a role for astrocytic NMDA receptors?
AB  - Kynurenine aminotransferase II (KAT-II) is the astrocytic enzyme catalyzing the
      synthesis of kynurenic acid (KYNA), an endogenous inhibitor of the alpha7
      nicotinic receptor and the NMDA receptor (NMDAr). A previous study demonstrated
      an increase of KYNA synthesis in the brain of rats with thioacetamide (TAA)
      induced acute liver failure. Here we show that TAA administration increases KAT
      II expression in the rat cerebral cortex and the effect is mimicked in cerebral
      cortical astrocytes in culture treated with high (5 mM) concentration of ammonia.
      KAT-II expression in control and TAA-treated rats was increased by NMDAr
      antagonist memantine, and the effects of TAA and memantine appeared additive. In
      astrocytes, the NMDAr antagonist MK-801 raised KAT-II expression as well, while
      NMDA added alone had no effect. Glutamate decreased KAT-II mRNA level, which was
      attenuated by MK-801. The results suggest that stimulation of KAT-II expression
      during hepatic encephalopathy may be associated with a partial inactivation of
      astrocytic NMDAr by ammonia.

PMID- 23132652
TI  - The distribution of transient receptor potential melastatin-8 in the rat soft
      palate, epiglottis, and pharynx.
AB  - Immunohistochemistry for transient receptor potential melastatin-8 (TRPM8), the
      cold and menthol receptor, was performed on the rat soft palate, epiglottis and
      pharynx. TRPM8-immunoreactive (IR) nerve fibers were located beneath the mucous
      epithelium, and occasionally penetrated the epithelium. These nerve fibers were
      abundant in the posterior portion of the soft palate and at the border region of
      naso-oral and laryngeal parts of the pharynx. The epiglottis was free from such
      nerve fibers. The double immunofluorescence method demonstrated that TRPM8-IR
      nerve fibers in the pharynx and soft palate were mostly devoid of calcitonin gene
      related peptide-immunoreactivity (CGRP-IR). The retrograde tracing method also
      demonstrated that 30.1 and 8.7 % of sensory neurons in the jugular and petrosal
      ganglia innervating the pharynx contained TRPM8-IR, respectively. Among these
      neurons, the co-expression of TRPM8 and CGRP-IR was very rare. In the nodose
      ganglion, however, pharyngeal neurons were devoid of TRPM8-IR. Taste bud-like
      structures in the soft palate and pharynx contained 4-9 TRPM8-IR cells. In the
      epiglottis, the mucous epithelium on the laryngeal side had numerous TRPM8-IR
      cells. The present study suggests that TRPM8 can respond to cold stimulation when
      food and drinks pass through oral and pharyngeal cavities.

PMID- 23132653
TI  - Robotic cancer surgery.

PMID- 23132654
TI  - Host-guest complexes between cryptophane-C and chloromethanes revisited.
AB  - Cryptophane-C is composed of two nonequivalent cyclotribenzylene caps, one of
      which contains methoxy group substituents on the phenyl rings. The two caps are
      connected by three OCH(2)CH(2)O linkers in an anti arrangement. Host-guest
      complexes of cryptophane-C with dichloromethane and chloroform in solution were
      investigated in detail by nuclear magnetic resonance techniques and density
      functional theory (DFT) calculations. Variable temperature proton and carbon-13
      spectra show a variety of dynamic processes, such as guest exchange and host
      conformational transitions. The guest exchange was studied quantitatively by
      exchange spectroscopy measurements or by line-shape analysis. The conformational
      preferences of the guest-containing host were interpreted through cross
      relaxation measurements, providing evidence of the gauche+2 and gauche-2
      conformations of the linkers. In addition, the mobility of the chloroform guest
      inside the cavity was studied by carbon-13 relaxation experiments. Combining
      different types of evidence led to a detailed picture of molecular recognition,
      interpreted in terms of conformational selection.

PMID- 23132655
TI  - Several 'problem nutrients' are identified in complementary feeding of Guatemalan
      infants with continued breastfeeding using the concept of 'critical nutrient
      density'.
AB  - BACKGROUND/OBJECTIVES: The World Health Organization (WHO) recommends
      nutritionally adequate complementary feeding (CF) through the introduction of
      indigenous foodstuffs and local foods while breastfeeding for at least 2 years.
      To determine the adequacy of the contribution of CF to the diets of Guatemalan
      infants at the 7th-12th month of life receiving high-intensity continued
      breastfeeding. SUBJECTS/METHODS: Critical nutrient densities for CF were modelled
      using age- and sex-specific energy and protein requirements assuming children to
      be at the 50th weight percentile of local peers and 15th weight percentiles of
      the 2006 WHO standards. Nutrient requirements for the total diet were determined
      using the recommended nutrient intakes. Breast milk was assumed to provide 75% of
      total energy at the 7th-9th month and 50% at the 10th-12th month. Gaps between
      computed critical nutrient densities and the CF consumption of 128 Guatemalan
      infants based on data collected by means of three nonconsecutive 24-h
      quantitative intake recalls were examined. Locally consumed foods with nutrient
      densities above the modelled critical densities were identified. RESULTS:
      Observed non-breast milk complementation would result in total diets providing
      inadequate nutrient density for vitamin A, niacin and vitamin C in some age
      groups. Major gaps for calcium, iron and zinc were ubiquitous across all groups.
      Few foods commonly consumed among Guatemalan infants had adequate densities of
      'problem nutrients'. CONCLUSIONS: The critical nutrient density concept is useful
      to evaluate the nutrient adequacy of the infant's diet. Fortified foods are
      essential sources of the main 'problem nutrients', namely calcium, iron and zinc,
      given that natural sources are scarce.

PMID- 23132656
TI  - Effect of asiatic and ursolic acids on morphology, hydrophobicity, and adhesion
      of UPECs to uroepithelial cells.
AB  - Adhesion of bacteria to epithelial tissue is an essential step in the progression
      of the urinary tract infections. Reduction of virulence factors responsible for
      microbial attachment may help to decrease or inhibit colonization of the host
      organism by pathogens. In the age of increasing bacterial antibiotic resistance,
      more and more attention is being paid to the use of plants and/or their bioactive
      components in the prevention and treatment of human infections. Asiatic acid (AA)
      and ursolic acid (UA), two plant secondary metabolites, were used as potential
      antibacterial agents. The current study aimed to determine the possible impact of
      AA and UA on morphology, hydrophobicity, and adhesion of clinical uropathogenic
      Escherichia coli strains (UPEC) to the uroepithelial cells. Our work describes
      for the first time the effects exerted by AA and UA on virulence factors of
      UPECs. The impact of both acids on the cell surface hydrophobicity of the
      investigated strains was very weak. The results clearly show the influence of AA
      and UA on the presence of P fimbriae and curli fibers, morphology of the UPECs
      cells and their adhesion to epithelium; however, some differences between
      activities of AA and UA were found.

PMID- 23132657
TI  - Molecular identification of an arsenic four-gene operon in Campylobacter lari.
AB  - An arsenic (ars) four-gene operon, containing genes encoding a putative membrane
      permease (ArsP), a transcriptional repressor (ArsR), an arsenate reductase (ArsC)
      and an arsenical-resistance membrane transporter (Acr3) was first identified in
      urease-positive thermophilic Campylobacter (UPTC) isolate, CF89-12. UPTC CF89-12
      and some other Campylobacter lari isolates contained their ars four-genes,
      similarly, differing from that in the reference C. lari RM2100 strain. Two
      putative promoters and a putative terminator were identified for the operon in
      UPTC CF89-12. In vivo transcription of the operon was confirmed in the UPTC
      cells. PCR experiments using two primer pairs designed in silico to amplify two
      arsR and arsC-acr3 segments, respectively, generated two amplicons, approximately
      200 and 350 base pairs, with all 31 of 31 and 19 of 31 C. lari isolates (n = 17
      for UPTC; n = 14 for UN C. lari), respectively. An inverted repeat forming a dyad
      structure, a potential binding site for a transcriptional repressor, was
      identified in the promoter region. Within the deduced 61 amino acids sequence of
      the putative arsR open reading frame from the UPTC CF89-12, a metal binding box
      and a DNA-binding helix-turn-helix motif were identified. The UPTC CF89-12 and
      some other UPTC isolates isolated from natural environment were resistant to
      arsenate.

PMID- 23132658
TI  - Breath holding duration and self-reported smoking abstinence intolerance as
      predictors of smoking lapse behavior in a laboratory analog task.
AB  - INTRODUCTION: Distress intolerance (DI) is elevated in smokers and confers
      increased risk for relapse following a quit attempt. Intolerance of respiratory
      distress and of nicotine withdrawal may be particularly relevant predictors of
      smoking cessation outcomes. However, no studies to date have examined the
      association between smoking relevant DI and smoking lapse behavior in a
      laboratory setting. The current study examined whether DI was associated with the
      risk of initiating smoking in a laboratory-based lapse analog task. METHODS: This
      study is a secondary data analysis from a study of the impact of alcohol
      administration on smoking behavior. Ninety-six cigarette smokers completed
      measures of DI and a smoking lapse analog task. Breath holding (BH) duration and
      self-reported intolerance of smoking abstinence were analyzed as predictors of
      smoking initiation in a survival analysis model. RESULTS: Shorter BH duration was
      associated with greater risk of smoking initiation, controlling for nicotine
      dependence, nicotine withdrawal symptoms, and demographics. Self-report measures
      of smoking abstinence DI were not associated with BH duration or time to smoking
      initiation when controlling for nicotine dependence severity. CONCLUSIONS: BH
      captures a domain of DI that is specifically associated with a higher risk of
      initiating smoking in this analog of smoking lapse. The prediction of smoking in
      an analog lapse task adds to the extant literature identifying an association
      between DI and smoking lapse and may enable further research to understand and
      address the mechanism through which BH affects smoking lapse risk.

PMID- 23132659
TI  - Sustainment of smoking cessation programs in substance use disorder treatment
      organizations.
AB  - INTRODUCTION: The majority of individuals who enter substance use disorder (SUD)
      treatment also use tobacco. Integrating smoking cessation services into SUD
      treatment may have substantial public health benefits, but few studies have
      examined whether organizations offering counseling-based smoking cessation
      programs sustain them over time. METHODS: This study examines sustainment of
      smoking cessation programs using 2 waves of data collected from 150 SUD treatment
      organizations. Data were collected in 2006-2008 and 2009-2010 using face-to-face
      interviews, telephone interviews, and mailed surveys. Logistic regression models
      of sustainment were estimated with administrators' attitudes toward smoking
      cessation and organizational barriers as covariates. RESULTS: About 60.2% of
      these SUD treatment organizations sustained their counseling-based smoking
      cessation programs at follow-up. Sustainment was significantly more likely when
      administrators' baseline attitudes about the impact of smoking cessation on
      recovery were more supportive (odds ratio, OR = 1.84; 95% confidence interval, CI
      = 1.13-3.01; p =.015) and when programs were accredited (OR = 3.95, 95% CI = 1.65
      9.50, p =.002). Worsening over time of barriers encompassing staff interest,
      staff skills, and competing treatment demands were negatively associated with
      sustainment (OR = 0.58, 95% CI = 0.42-0.81, p =.001). CONCLUSIONS: These findings
      provided empirical support for theoretical perspectives regarding the importance
      of leadership and staff expertise in promoting sustainment of innovations over
      time. Although the majority of SUD treatment organizations sustained their
      smoking cessation programs, the 40% rate of discontinuation is concerning and
      highlights the ongoing challenges faced by tobacco control efforts in substance
      abuse treatment.

PMID- 23132660
TI  - PITX2: a promising predictive biomarker of patients' prognosis and
      chemoradioresistance in esophageal squamous cell carcinoma.
AB  - The paired-like homeodomain transcription factor 2 (PITX2), a downstream effector
      of wnt/beta-catenin signaling, is well known to play critical role during normal
      embryonic development. However, the possible involvement of PITX2 in human
      tumorigenesis remains unclear. In this study, we extend its function in human
      esophageal squamous cell carcinoma (ESCC). The real-time PCR, Western blotting
      and immunohistochemistry (IHC) methods were applied to examine expression pattern
      of PITX2 in two different cohorts of ESCC cases treated with definitive
      chemoradiotherapy (CRT). Receiver operating characteristic (ROC) curve analysis
      was used to determine the cutoff point for PITX2 high expression in the training
      cohort. The ROC-derived cutoff point was then subjected to analyze the
      association of PITX2 expression with patients' survival and clinical
      characteristics in training and validation cohort, respectively. The expression
      level of PITX2 was significantly higher in ESCCs than that in normal esophageal
      mucosa. There was a positive correlation between PITX2 expression and clinical
      aggressiveness of ESCC. Importantly, high expression of PITX2 was observed more
      frequently in CRT resistant group than that in CRT effective group (p < 0.05).
      Furthermore, high expression of PITX2 was associated with poor disease-specific
      survival (p < 0.05) in ESCC. Then, the MTS, clonogenic survival fraction and cell
      apoptosis experiments showed that knockdown of PITX2 substantially increased ESCC
      cells sensitivity to ionizing radiation (IR) or cisplatin in vitro. Thus, the
      expression of PITX2, as detected by IHC, may be a useful tool for predicting CRT
      resistance and serves as an independent molecular marker for poor prognosis of
      ESCC patients treated with definite CRT.

PMID- 23132661
TI  - Relationship between lifestyle choices and hyperuricemia in Chinese men and
      women.
AB  - We aimed to explore correlations between lifestyle choices and hyperuricemia in a
      large Chinese population, emphasizing the differences from opposite sex. Ten
      thousand four hundred fifty subjects were randomly recruited from Tianjin
      municipality in China. Hyperuricemia was defined as serum uric acid >420 MUmol/L
      for men and >360 MUmol/L for women. Demographic data, highest education degree,
      work type, commuting means, smoking and drinking status, exercise frequency, and
      quantitative assessments of dietary factors were collected. Anthropometric
      measurements and fasting blood tests were performed. Statistical analyses were
      conducted. Total hyperuricemic prevalence was 12.89 %, with male significantly
      higher than female. Body mass index, waist circumference, serum indices, and age
      displayed high correlation coefficients, and most lifestyle factors also showed
      significant correlations as well. Binary logistic regression models showed odds
      ratio of developing hyperuricemia were much greater in males than in females by
      eating habits. However, physical activity-related lifestyle choices tended to
      cast much greater influences on the likelihood of hyperuricemia in females.
      Lifestyle choices and hyperuricemia are closely related. For males, eating habits
      have greater influences on the likelihood of developing hyperuricemia. For
      females, lifestyle factors like work type, commuting method, and exercise have
      such effects.

PMID- 23132662
TI  - Overtreatment can be cured only by education.

PMID- 23132664
TI  - Major active components in grapefruit, orange, and apple juices responsible for
      OATP2B1-mediated drug interactions.
AB  - We aimed to explore the major active components in grapefruit juice (GFJ), orange
      juice (OJ), and apple juice (AJ) that are responsible for OATP2B1-mediated drug
      interactions, by means of in vitro studies using Xenopus oocytes expressing
      OATP2B1 with a typical OATP2B1 substrate, estrone-3-sulfate. All three juices
      inhibited OATP2B1-mediated estrone-3-sulfate uptake with half-maximum inhibition
      (IC(50) ) values of 0.222% (GFJ), 0.807% (OJ), and 2.27% (AJ). Eight major
      flavonoids (naringin, naringenin, hesperidin, hesperetin, phloridzin, phloretin,
      quercetin, and kaempferol) contained in the juices inhibited OATP2B1-mediated
      estrone-3-sulfate uptake with IC(50) values of 4.63, 49.2, 1.92, 67.6, 23.2,
      1.31, 9.47, and 21.3 uM, respectively. When the concentration-IC(50) ratios
      ([C]/IC(50) ) of these flavonoids in GFJ, OJ, and AJ were calculated, values of
      [C]/IC(50) >= 100 were obtained for naringin in GFJ and hesperidin in OJ. No
      flavonoid in AJ showed a ratio higher than unity. However, significant inhibition
      of OATP2B1 was observed with a mixture of phloridzin, phloretin, hesperidin, and
      quercetin at the concentrations present in AJ. In conclusion, our results
      indicate that naringin and hesperidin are the major OATP2B1 inhibitors in GFJ and
      OJ, respectively, whereas a combination of multiple components appears to be
      responsible for OATP2B1 inhibition by AJ.

PMID- 23132663
TI  - Empiric therapy directed against MRSA in patients admitted to the intensive care
      unit does not improve outcomes in community-acquired pneumonia.
AB  - PURPOSE: The Infectious Diseases Society of America has recommended empiric
      therapy active against methicillin-resistant Staphylococcus aureus (MRSA) for all
      community-acquired pneumonia (CAP) patients admitted to the intensive care unit
      (ICU). However, there is sparse data to support this recommendation. The
      objective of our study was to ascertain if such a practice improves outcomes.
      METHODS: This study was a secondary, retrospective analysis of the Community
      Acquired Pneumonia Organization (CAPO) international database on CAP. Outcomes in
      patients admitted to the ICU were compared according to empiric initiation of
      anti-MRSA therapy (vancomycin or linezolid) with standard ICU CAP therapy (MRSA
      therapy group) or standard therapy alone for ICU CAP (standard therapy group).
      RESULTS: A total of 621 patients were identified with ICU pneumonia, of whom 57
      patients had been initiated empirically on vancomycin or linezolid (MRSA therapy
      group). Patients of the MRSA therapy group had more comorbidities and were more
      severely ill than those of the standard therapy group. However, there were no
      statistical differences between the MRSA therapy group and standard therapy group
      for the primary outcomes of in-hospital and 28-day mortality, length of stay and
      time to clinical stability. CONCLUSIONS: These findings suggest that empiric MRSA
      therapy in all ICU CAP patients may not improve outcomes and argue for clinician
      review of local epidemiologic trends on MRSA prevalence to ascertain the need for
      empiric MRSA coverage.

PMID- 23132665
TI  - On the moderating role of age in the relationship between pain and cognition.
AB  - BACKGROUND: A relationship between pain perception and cognitive function is
      evident. However, the directionality of this association is unclear and may be
      influenced by age. That is, inverse associations between pain and cognition have
      been reported in young and middle-aged chronic pain patients, whereas higher
      clinical pain ratings have been associated with better cognitive performance in
      older chronic pain patients. Therefore, this study examined the possible
      moderating role of age in the pain-cognition relationship. METHOD: Twenty-two
      younger and 24 older chronic pain participants completed neuropsychological tests
      of psychomotor speed, memory and executive function. They also completed the
      McGill Pain Questionnaire to evaluate clinical pain. RESULTS: Interaction
      analyses revealed that age indeed moderates the relationship between clinical
      pain ratings and cognitive functions. In the younger age group, pain ratings were
      inversely related to memory and executive function. In the older age group, a
      positive relationship was found between pain ratings and executive function,
      whereas the inverse association of clinical pain with memory was no longer
      present. CONCLUSIONS: This study was the first to confirm the hypothesis that age
      is an important moderator of the relationship between pain and cognition. An
      important finding is that in older adults, most inverse effects of pain on
      cognition are either no longer present or may even be reversed. The positive
      relationship between pain and executive function may indicate age-related reduced
      integrity of a shared underlying neural substrate.

PMID- 23132667
TI  - Topical problems of biophotonics.

PMID- 23132668
TI  - Near-infrared imaging of breast cancer using optical contrast agents.
AB  - Breast cancer is the most common malignancy in women worldwide and the second
      leading cause of cancer death. On the basis of three studies performed by our
      group, this article reviews the current status of optical breast imaging using
      extrinsic contrast agents. To date, only two contrast agents have been applied in
      human studies, indocyanine green (ICG) and omocianine. Both contrast media were
      used for absorption and fluorescence imaging. Generally speaking, malignant
      breast lesions exhibited higher absorption contrast as well as higher
      fluorescence contrast compared to benign lesions or non-diseased breast tissue.
      Some groups consider early enhancement characteristics helpful for
      differentiation between malignant and benign lesions. Late fluorescence ICG
      imaging - capitalizing on the extravasation of the dye through the wall of
      tumorous vessels - seems to be a promising technique to distinguish malignant
      from benign breast lesions.

PMID- 23132671
TI  - Limited capacity for acclimation of thermal physiology in a salamander,
      Desmognathus brimleyorum.
AB  - Habitats vary in temperature both spatially and temporally. Variation in thermal
      habitat introduces challenges to organisms and may reduce fitness unless
      organisms can physiologically adjust to such changes. Theory predicts that
      thermal variability should influence the capacity for acclimation such that
      increased variation should favor a reduction in the thermal sensitivity of
      physiological traits. In this study, we investigated acclimation to constant and
      variable conditions in populations of the salamander Desmognathus brimleyorum
      from the Ouachita Mountains of Arkansas, USA. We exposed salamanders to constant
      and variable temperature regimes for 8 weeks in the laboratory. We then tested
      salamanders for acclimation of thermal tolerance, and the thermal sensitivities
      of swimming performance and standard metabolic rate. Our results indicate limited
      capacity for thermal acclimation to constant and variable conditions in D.
      brimleyorum. Instead, variation in physiological traits is dominated by
      differences among populations. Population differences do not appear to be
      correlated with observed variation in the thermal conditions of the streams, but
      are likely a consequence of structural and ecological differences. Due to the
      mixed support for theoretical predictions for acclimation to alternative
      environments, further consideration should be given to revising and expanding
      current theoretical models.

PMID- 23132672
TI  - Individual- and school-level sociodemographic predictors of obesity among New
      York City public school children.
AB  - To identify student- and school-level sociodemographic characteristics associated
      with overweight and obesity, the authors conducted cross-sectional analyses of
      data from 624,204 public school children (kindergarten through 12th grade) who
      took part in the 2007-2008 New York City Fitnessgram Program. The overall
      prevalence of obesity was 20.3%, and the prevalence of overweight was 17.6%. In
      multivariate models, the odds of being obese as compared with normal weight were
      higher for boys versus girls (odds ratio (OR) = 1.39, 95% confidence interval
      (CI): 1.36, 1.42), for black (OR = 1.11, 95% CI: 1.07, 1.15) and Hispanic (OR =
      1.48, 95% CI: 1.43, 1.53) children as compared with white children, for children
      receiving reduced-price (OR = 1.17, 95% CI: 1.13, 1.21) or free (OR = 1.12, 95%
      CI: 1.09, 1.15) school lunches as compared with those paying full price, and for
      US-born students (OR = 1.54, 95% CI: 1.50, 1.58) as compared with foreign-born
      students. After adjustment for individual-level factors, obesity was associated
      with the percentage of students who were US-born (across interquartile range
      (75th percentile vs. 25th), OR = 1.10, 95% CI: 1.07, 1.14) and the percentage of
      students who received free or reduced-price lunches (across interquartile range,
      OR = 1.13, 95% CI: 1.10, 1.18). The authors conclude that individual
      sociodemographic characteristics and school-level sociodemographic composition
      are associated with obesity among New York City public school students.

PMID- 23132674
TI  - Child patterns of growth delay and cognitive development in a Bolivian mining
      city.
AB  - OBJECTIVES: This study aims to (1) follow up and characterize infant growth
      patterns during the first year of life in Bolivia, and (2) determine whether
      there exists an association between weight gain and cognitive development in
      children living near contaminated mining industries. METHODS: Data on 175
      children participating to the ToxBol (Toxicity in Bolivia) birth cohort were
      analyzed. Rapid-growth during the first 6 months was defined as a change in
      weight z-score > 0.67 while slow-growth was defined as a weight z-score change of
      < -0.67. Neurodevelopment was evaluated using the Bayley Scales of Infant
      Development at 10.5-12.5 months of age. Mixed models were used to examine the
      association between cognitive development and weight gain. RESULTS: Rapid growers
      weighed less at birth (P < 0.01). However, they revealed a higher body mass index
      at 12 months of age (0.70 +/- 0.73, P < 0.01). After adjustment for confounding,
      rapid growth was not associated with cognitive development (coef = 0.49, 95%
      confidence interval = -4.10, 5.08). CONCLUSIONS: In this Bolivian cohort,
      children born smaller were more likely to grow/develop faster and attain greater
      weight and length. Their cognitive development was not affected by their growth
      patterns.

PMID- 23132673
TI  - Diabetes and obesity-related genes and the risk of neural tube defects in the
      national birth defects prevention study.
AB  - Few studies have evaluated genetic susceptibility related to diabetes and obesity
      as a risk factor for neural tube defects (NTDs). The authors investigated 23
      single nucleotide polymorphisms among 9 genes (ADRB3, ENPP1, FTO, LEP, PPARG,
      PPARGC1A, SLC2A2, TCF7L2, and UCP2) associated with type 2 diabetes or obesity.
      Samples were obtained from 737 NTD case-parent triads included in the National
      Birth Defects Prevention Study during 1999-2007. Log-linear models were used to
      evaluate maternal and offspring genetic effects. After application of the false
      discovery rate, there were 5 significant maternal genetic effects. The less
      common alleles at the 4 FTO single nucleotide polymorphisms showed a reduction of
      NTD risk (for rs1421085, relative risk (RR) = 0.73 (95% confidence interval (CI):
      0.62, 0.87); for rs8050136, RR = 0.79 (95% CI: 0.67, 0.93); for rs9939609, RR =
      0.79 (95% CI: 0.67, 0.94); and for rs17187449, RR = 0.80 (95% CI: 0.68, 0.95)).
      Additionally, maternal LEP rs2071045 (RR = 1.31, 95% CI: 1.08, 1.60) and
      offspring UCP2 rs660339 (RR = 1.32, 95% CI: 1.06, 1.64) were associated with NTD
      risk. Furthermore, the maternal genotype for TCF7L2 rs3814573 suggested an
      increased NTD risk among obese women. These findings indicate that maternal
      genetic variants associated with glucose homeostasis may modify the risk of
      having an NTD-affected pregnancy.

PMID- 23132675
TI  - Mechanistic origin of the vibrational coherence accompanying the photoreaction of
      biomimetic molecular switches.
AB  - The coherent photoisomerization of a chromophore in condensed phase is a rare
      process in which light energy is funneled into specific molecular vibrations
      during electronic relaxation from the excited to the ground state. In this work,
      we employed ultrafast spectroscopy and computational methods to investigate the
      molecular origin of the coherent motion accompanying the photoisomerization of
      indanylidene-pyrroline (IP) molecular switches. UV/Vis femtosecond transient
      absorption gave evidence for an excited- and ground-state vibrational wave
      packet, which appears as a general feature of the IP compounds investigated. In
      close resemblance to the coherent photoisomerization of rhodopsin, the sudden
      onset of a far-red-detuned and rapidly blue-shifting photoproduct signature
      indicated that the population arriving on the electronic ground state after
      nonadiabatic decay through the conical intersection (CI) is still very focused in
      the form of a vibrational wave packet. Semiclassical trajectories were employed
      to investigate the reaction mechanism. Their analysis showed that coupled double
      bond twisting and ring inversions, already populated during the excited-state
      reactive motion, induced periodic changes in pi-conjugation that modulate the
      ground-state absorption after the non-adiabatic decay. This prediction further
      supports that the observed ground-state oscillation results from the reactive
      motion, which is in line with a biomimetic, coherent photoisomerization scenario.
      The IP compounds thus appear as a model system to investigate the mechanism of
      mode-selective photomechanical energy transduction. The presented mechanism opens
      new perspectives for energy transduction at the molecular level, with
      applications to the design of efficient molecular devices.

PMID- 23132676
TI  - High expression of Dickkopf-related protein 1 is related to lymphatic metastasis
      and indicates poor prognosis in intrahepatic cholangiocarcinoma patients after
      surgery.
AB  - BACKGROUND: Dickkopf-related protein 1 (DKK1) has been reported involved in
      metastasis and invasion in several tumors. This study sought to investigate the
      prognostic value of DKK1 in intrahepatic cholangiocarcinoma (ICC) and its role in
      promoting ICC metastasis. METHODS: Tissue microarrays of 138 ICC patient samples
      were employed to detect DKK1, vascular endothelial growth factor C (VEGF-C), and
      matrix metalloproteinase 9 (MMP9) expression using immunohistochemistry. The
      prognostic significances were assessed by Kaplan-Meier survival estimates. DKK1
      expression was measured in an ICC cell line (HCCC-9810) and ICC tissues by
      immunofluorescence assay, quantitative real-time polymerase chain reaction, and
      western blot. Serum levels of DKK1 from 37 ICC patients were tested by enzyme
      linked immunosorbent assay. The role of DKK1 in proliferation, migration,
      invasion, and gene expression regulation was assessed by DKK1 depletion using
      small interfering RNA. RESULTS: Multivariate analyses revealed that DKK1 was an
      unfavorable predictor for overall survival and time to recurrence. The prognostic
      significance was retained in ICC patients with low recurrence risk (P < .05).
      DKK1 expression was elevated in an ICC cell line, tumor samples, and patient
      sera. High levels of DKK1 in ICC tissues correlated with elevated MMP9, VEGF-C,
      and metastasis of hepatic hilar lymph nodes. DKK1 depletion caused a decrease in
      cell migration and invasiveness, and down-regulation of MMP9 and VEGF-C
      expression. CONCLUSIONS: DKK1 is a novel prognostic biomarker for ICC, and it
      enhances tumor cell invasion and promotes lymph node metastasis of ICC through
      the induction of MMP9 and VEGF-C. DKK1 may be a potential therapeutic target for
      ICC.

PMID- 23132677
TI  - Disordering of phospholipid headgroups induced by a small amount of polyethylene
      oxide.
AB  - We present a (31)P NMR spectroscopy study of planar glass-plate-oriented multi
      bilayers of dimyristoylphosphatidylcholine (DMPC) with addition of polyethylene
      oxide (PEO). This work revealed the presence of a new component in the spectra
      that appeared only with addition of a small fraction of PEO (up to one PEO
      segment per dimyristoylphosphatidylcholine molecule) and disappeared when larger
      amounts of PEO were added. We explained this phenomenon as an effect of an
      inhomogeneous force field induced by the PEO molecules located at a certain depth
      in the lipid membrane interface region.

PMID- 23132678
TI  - The base-free chemoselective ring opening of epoxides with carboxylic acids using
      [bmim]Br: a rapid entry into 1,2-diol mono-esters synthesis.
AB  - A facile and highly convenient base-free protocol for the chemoselective
      preparation of 1,2-diol mono-esters is described. In this method, the
      regioselective ring opening of epoxides with carboxylic acids in the presence of
      [bmim]Br furnishes the corresponding 1,2-diol mono-esters in excellent yields.
      This method is efficient for various structurally diverse epoxides and carboxylic
      acids and it can be efficiently applied for the scale up synthesis of 1,2-diol
      mono-esters in reasonable to good yields. [bmim]Br remarkably influences the
      reaction progress and acts as both solvent and catalyst in this protocol.

PMID- 23132679
TI  - The early development of face processing--what makes faces special?
AB  - In the present article we review behavioral and neurophysiological studies on
      face processing in adults and in early development. From the existing empirical
      and theoretical literature we derive three aspects that distinguish face
      processing from the processing of other visual object categories. Each of these
      aspects is discussed from a developmental perspective. First, faces are
      recognized and represented at the individual level rather than at the basic
      level. Second, humans typically acquire extensive expertise in individuating
      faces from early on in development. And third, more than other objects, faces are
      processed holistically. There is a quantitative difference in the amount of
      visual experience for faces and other object categories in that the amount of
      expertise typically acquired for faces is greater than that for other object
      categories. In addition, we discuss possible qualitative differences in
      experience for faces and objects. For instance, there is evidence for a sensitive
      period in infancy for building up a holistic face representation and for
      perceptual narrowing for faces of one's own species and race. We conclude our
      literature review with questions for future research, for instance, regarding the
      exact relationship between behavioral and neuronal markers of face processing
      across development.

PMID- 23132680
TI  - Aggravated inflammation and increased expression of cysteinyl leukotriene
      receptors in the brain after focal cerebral ischemia in AQP4-deficient mice.
AB  - OBJECTIVE: Aquaporin-4 (AQP4), the main water channel protein in the brain, plays
      a critical role in water homeostasis and brain edema. Here, we investigated its
      role in the inflammatory responses after focal cerebral ischemia. METHODS: In
      AQP4-knockout (KO) and wild-type mice, focal cerebral ischemia was induced by 30
      min of middle cerebral arterial occlusion (MCAO). Ischemic neuronal injury and
      cellular inflammatory responses, as well as the expression and localization of
      cysteinyl leukotriene CysLT(2) and CysLT(1) receptors, were determined at 24 and
      72 h after MCAO. RESULTS: AQP4-KO mice showed more neuronal loss, more severe
      microglial activation and neutrophil infiltration, but less astrocyte
      proliferation in the brain after MCAO than wild-type mice. In addition, the
      protein levels of both CysLT(1) and CysLT(2) receptors were up-regulated in the
      ischemic brain, and the up-regulation was more pronounced in AQP4-KO mice. The
      CysLT(1) and CysLT(2) receptors were primarily localized in neurons, microglia
      and neutrophils; those localized in microglia and neutrophils were enhanced in
      AQP4-KO mice. CONCLUSION: AQP4 may play an inhibitory role in postischemic
      inflammation.

PMID- 23132681
TI  - Antigenotoxic effect of lipoic acid against mitomycin-C in human lymphocyte
      cultures.
AB  - Antitumor agents are used in therapy against many forms of human cancer. One of
      these is mitomycin-C (MMC). As with many agents, it can interact with biological
      molecules and can induce genetic hazards in non-tumor cells. One of the possible
      approaches to protect DNA from this damage is to supply antioxidants that can
      remove free radicals produced by antitumor agents. Lipoic acid (LA) is known as
      one of the most powerful antioxidants. The aim of this study was to investigate
      antigenotoxic effects of LA against MMC induced chromosomal aberrations (CA),
      sister chromatid exchanges (SCE) and micronucleus (MN) formation in human
      lymphocytes. Lymphocytes were treated with 0.2 MUg MMC/heparinized mL for 48 h.
      Three different concentrations (0.5, 1, 2 MUg/mL) of LA were used together with
      MMC in three different applications; 1 h pre-treatment, simultaneous treatment
      and 1 h post-treatment. A negative, a positive and a solvent control were also
      included. In all the cultures treated with MMC + LA, the frequency of abnormal
      cells and CA/cell significantly decreased compared to MMC. Statistically
      significant reduction was also observed in SCE/cell and MN frequencies in all
      treatments. These results demonstrated anticlastogenic and antimutagenic effects
      of LA against MMC induced genotoxicity. LA showed the most efficient effect
      during 1 h pretreatment. On the other hand, MMC + LA treatments induced
      significant reduction in mitotic index than that of MMC treatment alone. These
      results are encouraging that LA can be a possible chemopreventive agent in
      tumorigenesis in both cancer patients and in health care persons handling anti
      cancer drugs. 

PMID- 23132682
TI  - Nucleofection of whole murine retinas.
AB  - The mouse retina constitutes an important research model for studies aiming to
      unravel the cellular and molecular mechanisms underlying ocular diseases. The
      accessibility of this tissue and its feasibility to directly obtain neurons from
      it has increased the number of studies culturing mouse retina, mainly retinal
      cell suspensions. However, to address many questions concerning retinal diseases
      and protein function, the organotypic structure must be maintained, so it becomes
      important to devise methods to transfect and culture whole retinas without
      disturbing their cellular structure. Moreover, the postmitotic stage of retinal
      neurons makes them reluctant to commonly used transfection techniques. For this
      purpose some published methods employ in vivo virus-based transfection techniques
      or biolistics, methods that present some constraints. Here we report for the
      first time a method to transfect P15-P20 whole murine retinas via nucleofection,
      where nucleic acids are directly delivered to the cell nuclei, allowing in vitro
      transfection of postmitotic cells. A detailed protocol for successful retina
      extraction, organotypic culture, nucleofection, histological procedures and
      imaging is described. In our hands the A-33 nucleofector program shows the
      highest transfection efficiency. Whole flat-mount retinas and cryosections from
      transfected retinas were imaged by epifluorescence and confocal microscopy,
      showing that not only cells located in the outermost retinal layers, but also
      those in inner retinal layers are transfected. In conclusion, we present a novel
      method to successfully transfect postnatal whole murine retina via nucleofection,
      showing that retina can be successfully nucleofected after some optimization
      steps. 

PMID- 23132683
TI  - A strategy for designing a concave Pt-Ni alloy through controllable chemical
      etching.
AB  - This corrosion: Octahedral Pt-Ni alloy nanoparticles (NPs) are converted into
      concave Pt(3)Ni NPs by a coordination-assisted chemical-etching process. The
      corroded concave Pt-Ni NPs have a higher density of low-coordinate atoms in steps
      sites, a decisive property in heterogeneous catalysis.

PMID- 23132684
TI  - Exploring frontal asymmetry using functional near-infrared spectroscopy: a
      preliminary study of the effects of social anxiety during interaction and
      performance tasks.
AB  - Preliminary studies examining brain function associated with social anxiety
      suggest the possibility of right-sided prefrontal activation associated with
      phobic stimulation. Although most existing neuroimaging techniques preclude
      participants from engaging in ecologically valid social tasks during assessment,
      functional near-infrared spectroscopy (fNIRS) is a promising new technique that
      permits such assessment. The present study investigated the utility of the fNIRS
      procedure and explored frontal asymmetry during in vivo social challenge tasks
      among female undergraduate students who scored in top and bottom percentiles on a
      social anxiety screening measure. Results revealed that participants in both
      groups experienced a significant increase in concentration of blood volume and
      oxygenated hemoglobin in the right hemisphere compared to the left hemisphere
      while giving a speech. Non-hemispheric effects were also observed. In addition,
      the high anxiety group showed a non-significant trend toward greater right
      frontal activity than the low anxiety group. This study highlights the utility of
      the fNIRS device in successfully assessing real-time changes in cerebrovascular
      response as a function of naturalistic social behavior, and supports the
      potential utility of this technology in the study of the neurophysiology of
      social anxiety.

PMID- 23132685
TI  - [Motivational interviewing in psychiatry].
AB  - Motivational Interviewing and associated communication techniques and
      intervention methods have been widely applied in patients with substance use
      disorder and other psychiatric disorders in the last twenty years. Intensive
      research on effectiveness and underlying mechanisms as well as the increasing
      efforts to apply MI in other psychiatric disorders has lead to a large number of
      scientific publications in this field. MI has been shown to be effective in
      situations where the patient's ambivalence seems to impede the therapeutic
      process. Communication skills and the ability of the care taker to induce the so
      called "change talk" by the patient play a particularly important role and
      correlate with the positive effects of MI. Those groups of patients in which
      other factors than ambivalence affect the therapeutic process seem to benefit
      much less from this intervention method. MI hallmarks the substantial change that
      gradually took place during the last two decades in caretakers' attitude towards
      patients with dependence and other psychiatric patients: away from "prescriptive"
      towards "supportive" treatment and communication style. Therefore, it seems to be
      reasonable to implement the basics of MG in the training curricula for
      psychiatrists.

PMID- 23132686
TI  - Crystallization of amorphous solid dispersions of resveratrol during preparation
      and storage-Impact of different polymers.
AB  - The objective of this study was to investigate intermolecular interactions
      between resveratrol and polymers in amorphous blends and to study the potential
      correlations between compound-polymer interactions, manufacturability, and
      stability of the amorphous system to crystallization during storage. Polymers
      included two grades of poly (vinylpyrrolidone) (PVP), Eudragit E100 (E100),
      hydroxypropyl methylcellulose (HPMC), hydroxypropyl methylcellulose acetate
      succinate (HPMCAS), carboxymethyl cellulose acetate butyrate, and poly (acrylic
      acid) (PAA). Amorphous blends ("solid dispersions") were prepared by dissolving
      both resveratrol and polymer in a solvent followed by rotary evaporation.
      Crystallinity was evaluated using X-ray powder diffraction and was studied as a
      function of time. Mid-infrared (IR) spectroscopy was used to investigate
      resveratrol-polymer interactions. Polymer influence on the crystallization
      behavior of resveratrol varied and could be correlated to the polymer structure,
      whereby polymers with good hydrogen bond acceptor groups performed better as
      crystallization inhibitors. Resveratrol-polymer hydrogen bonding interactions
      could be inferred from the IR spectra. Somewhat surprisingly, E100 and
      resveratrol showed evidence of an acid-base reaction, in addition to
      intermolecular hydrogen bonding interactions. PVP K29/32 appeared to form
      stronger hydrogen bond interactions with resveratrol relative to HPMC, HPMCAS,
      and PAA, consistent with acceptor group chemistry. Long-term stability of the
      systems against crystallization suggested that stability is linked to the type
      and strength of intermolecular interactions present. whereby resveratrol blended
      with E100 and PVP K29/32 showed the greatest stability to crystallization. In
      conclusion, amorphous resveratrol is unstable and difficult to form, requiring
      the assistance of a polymeric crystallization inhibitor to facilitate the
      formation of an amorphous solid dispersion. Polymers effective at inhibiting
      crystallization were identified, and it is rationalized that their effectiveness
      is based on the type and strength of their intermolecular interactions with
      resveratrol.

PMID- 23132687
TI  - Inverse gradients in leaf wax deltaD and delta13C values along grass blades of
      Miscanthus sinensis: implications for leaf wax reproduction and plant physiology.
AB  - Compound specific hydrogen and carbon isotopic ratios of higher plant leaf waxes
      have been extensively used in paleoclimate and paleoenvironmental
      reconstructions. However, studies so far have focused on the comparison of leaf
      wax isotopic differences in bulk leaf samples between different plant species. We
      sampled three different varieties of tall grasses (Miscanthus sinensis) in six
      segments from base to tip and determined hydrogen and carbon isotopic ratios of
      leaf waxes, as well as hydrogen and oxygen isotopic ratios of leaf water samples.
      We found an increasing, base-to-tip hydrogen isotopic gradient along the grass
      blades that can probably be attributed to active leaf wax regeneration over the
      growth season. Carbon isotopic ratios, on the other hand, show opposite trends to
      hydrogen isotopic ratios along the grass blades, which may reflect different
      photosynthetic efficiencies at different blade locales.

PMID- 23132688
TI  - Cat-scratch disease in Northern Italy: atypical clinical manifestations in humans
      and prevalence of Bartonella infection in cats.
AB  - In this paper, we report an investigation on cat-scratch disease (CSD) in
      Northern Italy. Seventy-four cases of CSD were diagnosed at the San Matteo
      hospital, Pavia, during the period 2005-2010. Of these 74 patients, 18 (24.3 %)
      reported atypical clinical manifestations such as ocular papillitis,
      maculopapular eruptions, vertebral infection, pulmonary infiltrates, and
      granulomatous hepatitis. Contact with cats was documented for 61 patients (82.4
      %), while cat-related trauma was reported for 49 patients (66.2 %). We
      subsequently investigated the presence of Bartonella infection in cats belonging
      to the above patients and in other domestic and stray cats from three provinces
      of Northern Italy. Among the 27 domestic cats tested, nine of the 11 belonging to
      the CSD patients and two of the remaining 16 were infected by B. henselae (81.8 %
      vs. 12.5 %). Out of over 1,300 stray cats examined, 23.1 % were seropositive for
      B. henselae; after culturing and genotyping, 17 % were found to be infected by B.
      henselae (15.5 %) or B. clarridgeiae (1.5 %).

PMID- 23132689
TI  - Molecular diagnosis of bacterial vaginosis: impact on IVF outcome.
AB  - Bacterial vaginosis can increase obstetrical complications such as miscarriage,
      premature rupture of membranes and preterm delivery. The aim of our study was
      first to assess BV prevalence for infertile patients treated by in vitro
      fertilisation (IVF) using both the Nugent score and polymerase chain reaction
      (PCR), and then to assess the impact of BV on the pregnancy rate after IVF.
      Vaginal samples were obtained from women followed for IVF in our Assisted
      Reproduction Technology (ART) Unit between August 2010 and April 2011. For each
      patient, two techniques were performed to diagnose BV: Gram staining to assess
      the Nugent score and a quantitative molecular analysis using a specific real-time
      PCR assay. Two groups were studied: normal flora (BV-) and BV (BV+). The primary
      outcome measure was the implantation rate. The secondary outcomes were clinical
      pregnancy rate, early and late miscarriage, premature rupture of membranes,
      preterm delivery, mode of delivery and birthweight. A total of 307 patients were
      included. PCR revealed a prevalence of BV of 9.45 %. Among women who performed
      vaginal douching, 22.2 % were BV+, whereas 7.9 % of patients who did not douche
      were BV+ (p = 0.028). The embryo implantation rate was decreased between the BV-
      and BV+ groups (36.3 % vs. 27.6 %, p = 0.418), but it was not significant.
      Obstetrical outcomes did not present significant statistical differences among
      the groups. Vaginal douching significantly enhanced BV in women treated with IVF.
      We also observed a non-significant decrease of embryo implantation rate and
      clinical pregnancy rate for women treated by IVF.

PMID- 23132690
TI  - Is Helicobacter pylori good or bad?
AB  - Helicobacter pylori remains a controversial organism with regards to humans, with
      its epidemiology still being unclear nearly two decades after its discovery. The
      association between H. pylori infection and subsequent development of chronic
      active gastritis, peptic ulcer disease, gastric cell carcinoma, and B cell mucosa
      associated lymphoid tissue (MALT) lymphoma has been well established. Current
      studies, however, suggest that fewer than 20 % of all infected patients will
      develop any consequences from their infection. Hence, should the infection be
      considered a disease not at all or, on the contrary, is the microorganism harmful
      in only some circumstances? This article attempts to weigh the currently
      available evidence supporting that H. pylori may be good and not always bad.

PMID- 23132691
TI  - Bifunctionalized hollow nanospheres for the one-pot synthesis of methyl isobutyl
      ketone from acetone.
AB  - Pd-doped propyl sulfonic acid-functionalized hollow nanospheres proved to be
      efficient bifunctionalized catalysts for the one-pot synthesis of methyl isobutyl
      ketone (MIBK) from acetone and hydrogen in liquid phase. These hollow nanospheres
      exhibited a higher activity than their bulk mesoporous counterparts (SBA-15 or
      FDU-12), mainly due to the short diffusion resistance of hollow nanospheres.
      Hollow nanospheres with silica frameworks showed higher activity and selectivity
      for MIBK than those with ethane-bridged frameworks, suggesting that hollow
      nanospheres with hydrophilic surface properties favor the formation of MIBK. This
      is probably due to the increased affinity of the hydrophilic surface towards
      acetone and its decreased affinity towards MIBK, which precludes deep
      condensation of MIBK with acetone. Under optimal conditions, up to 90 %
      selectivity for MIBK can be obtained with conversions of acetone as high as 43 %.
      This result is among the best reported so far for mesoporous silica-based
      catalysts. The control/fine-tuning of morphology and surface properties provides
      an efficient strategy for improving the catalytic performance of solid catalysts.

PMID- 23132692
TI  - Role of the RPS in alleviating symptoms of acute and chronic RDD.

PMID- 23132693
TI  - Cheap GP ultrasonography is not the answer to clinical breast examination.

PMID- 23132694
TI  - Assessment of cerebrovascular reactivity using real-time BOLD fMRI in children
      with moyamoya disease: a pilot study.
AB  - PURPOSE: This pilot study aims to test the reliability and clinical validity of
      the assessment of cerebrovascular reactivity (CVR) with real-time blood-oxygen
      level-dependent (BOLD) fMRI (rtCVR) in comparison with standard off-line
      processing in children with moyamoya disease. METHODS: Eight consecutive
      pediatric patients with moyamoya cerebral arteriopathy underwent BOLD fMRI CVR
      studies either on a 1.5-T or on a 3-T scanner with breath-holding techniques in
      six patients and under general anesthesia (GA) in three patients. One patient had
      undergone CVR study initially without and later with GA, and another had
      undergone CVR study before and after a revascularization procedure. The off-line
      and real-time processing of the data was done, and the results were compared for
      general quality and adequacy of the study (scale 0-3, 3 being the best) and for
      the presence or absence of abnormal reactivity and the location, pattern, and
      extent of abnormal reactivity. RESULTS: A total of 20 CVR series each was studied
      on real-time functional MRI and off-line analysis (eight patients, ten sessions,
      two series per session). All eight sessions done under GA were rated as quality
      class 3 (100 %), whereas only 5 of the 12 (41.7 %) studies with breath-holding
      technique were considered to be of best quality (class 3). In comparison to the
      off-line processing, the overall sensitivity of the rtCVR technique was 90 % with
      a specificity of 100 %. CONCLUSIONS: rtCVR assessment in children with moyamoya
      disease is feasible, and the results are comparable to that of standard off-line
      analysis. The results from off-line analysis are only available, at the earliest,
      several hours after the MRI has been completed. rtCVR can overcome this
      difficulty and may be equally reliable.

PMID- 23132695
TI  - Acupuncture in the context of diffuse noxious inhibitory control.

PMID- 23132697
TI  - Genetic and epigenetic states of the GNAS complex in pseudohypoparathyroidism
      type Ib using methylation-specific multiplex ligation-dependent probe
      amplification assay.
AB  - CONTEXT: Pseudohypoparathyroidism type Ib (PHP-Ib) is a rare disorder resulting
      from genetic and epigenetic aberrations in the GNAS complex. PHP-Ib, usually
      defined by renal resistance to parathyroid hormone, is due to a maternal loss of
      GNAS exon A/B methylation and leads to decreased expression of the stimulatory G
      protein alpha (Gsalpha) in specific tissues. OBJECTIVE: To clarify the usefulness
      of methylation-specific multiplex ligation-dependent probe amplification (MS
      MLPA), we evaluated genetic and epigenetic changes of the GNAS locus in Japanese
      PHP-Ib patients. DESIGN: Retrospective case series. PATIENTS: We studied 13
      subjects with PHP-Ib (three families with eight affected members and one
      unaffected member and four sporadic cases). MEASUREMENTS: The methylation status
      of GNAS differentially methylated regions (DMRs) was evaluated using MS-MLPA. The
      main outcome measure was the presence of deletion mutations in the GNAS locus and
      STX16, which were assessed using MLPA. RESULTS: In all familial PHP-Ib cases, a
      ~3 kb deletion of STX16 and demethylation of the A/B domain were identified. In
      contrast, no deletion was detected throughout the entire GNAS locus region in the
      sporadic cases. Broad methylation abnormalities were observed in the GNAS DMRs.
      CONCLUSIONS: MS-MLPA allows for precise and rapid analysis of the methylation
      status in GNAS DMRs as well as the detection of microdeletion mutations in PHP
      Ib. Results confirm the previous findings in this disorder and demonstrate that
      this method is valuable for the genetic evaluation and visualizing the
      methylation status. The MS-MLPA assay is a useful tool that may facilitate making
      the molecular diagnosis of PHP-Ib.

PMID- 23132696
TI  - Novel H6PDH mutations in two girls with premature adrenarche: 'apparent' and
      'true' CRD can be differentiated by urinary steroid profiling.
AB  - CONTEXT: Inactivating mutations in the enzyme hexose-6-phosphate dehydrogenase
      (H6PDH, encoded by H6PD) cause apparent cortisone reductase deficiency (ACRD).
      H6PDH generates cofactor NADPH for 11beta-hydroxysteroid dehydrogenase type 1
      (11beta-HSD1, encoded by HSD11B1) oxo-reductase activity, converting cortisone to
      cortisol. Inactivating mutations in HSD11B1 cause true cortisone reductase
      deficiency (CRD). Both ACRD and CRD present with hypothalamic-pituitary-adrenal
      (HPA) axis activation and adrenal hyperandrogenism. OBJECTIVE: To describe the
      clinical, biochemical and molecular characteristics of two additional female
      children with ACRD and to illustrate the diagnostic value of urinary steroid
      profiling in identifying and differentiating a total of six ACRD and four CRD
      cases. DESIGN: Clinical, biochemical and genetic assessment of two female
      patients presenting during childhood. In addition, results of urinary steroid
      profiling in a total of ten ACRD/CRD patients were compared to identify
      distinguishing characteristics. RESULTS: Case 1 was compound heterozygous for
      R109AfsX3 and a novel P146L missense mutation in H6PD. Case 2 was compound
      heterozygous for novel nonsense mutations Q325X and Y446X in H6PD. Mutant
      expression studies confirmed loss of H6PDH activity in both cases. Urinary
      steroid metabolite profiling by gas chromatography/mass spectrometry suggested
      ACRD in both cases. In addition, we were able to establish a steroid metabolite
      signature differentiating ACRD and CRD, providing a basis for genetic diagnosis
      and future individualised management. CONCLUSIONS: Steroid profile analysis of a
      24-h urine collection provides a diagnostic method for discriminating between
      ACRD and CRD. This will provide a useful tool in stratifying unresolved adrenal
      hyperandrogenism in children with premature adrenarche and adult females with
      polycystic ovary syndrome (PCOS).

PMID- 23132698
TI  - Active acromegaly is associated with decreased hs-CRP and NT-proBNP serum levels:
      insights from the Belgian registry of acromegaly.
AB  - OBJECTIVE: Patients with active acromegaly have an increased prevalence of
      cardiomyopathy and heart failure but a less than expected risk of coronary artery
      disease, considering the frequent association of diabetes mellitus and
      hypertension. We examined whether changes in high-sensitive C-reactive protein
      (hs-CRP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) might
      contribute to this phenomenon. DESIGN AND METHODS: Two hundred patients of the
      Belgian acromegaly registry (AcroBel) were divided in two groups: active disease
      (IGF1 Z-score >2; n=95) and controlled disease (IGF1 Z-score <=2; n=105). Serum
      levels of hs-CRP and NT-proBNP were measured and correlated with BMI, blood
      pressure, fasting lipids, fasting glucose and insulin, HbA1c, IGF1, interleukin 6
      (IL6), adiponectin, and sE-selectin. In a subset of acromegaly patients, hs-CRP,
      IL6, and NT-proBNP levels were also compared with those/the values of an age-,
      gender-, and BMI-matched reference group. RESULTS: Patients with active
      acromegaly had significantly lower levels of hs-CRP (median (interquartile
      range), 0.5 mg/l (0.1, 0.9) vs 1.3 mg/l (0.5, 4.1); P<0.001) and NT-proBNP, (47.0
      ng/l (26.0, 86.0) vs 71.0 ng/l (43.0, 184.0); P<0.001) compared with patients
      with controlled acromegaly. Compared with the reference population, hs-CRP was
      not different in controlled acromegaly but significantly lower in active
      acromegaly (median, 0.4 mg/l (0.1, 0.8) vs 1.4 mg/l (0.8, 2.9); P<0.001), while
      NT-proBNP was similar in active acromegaly but significantly higher in controlled
      acromegaly (66.5 ng/l (40.0, 119.5) vs 50.8 ng/l (26.5, 79.7); P<0.001).
      CONCLUSIONS: Patients with active acromegaly have significantly lower values of
      NT-proBNP and hs-CRP compared with patients with controlled disease and even
      lower values of hs-CRP compared with control subjects.

PMID- 23132699
TI  - Long-term follow-up of a large series of patients with type 1 gastric carcinoid
      tumors: data from a multicenter study.
AB  - OBJECTIVE: To study the clinical presentation, diagnostic approach, response to
      treatment, and the presence of other pathologies in patients with gastric
      carcinoid type 1 (GC 1) tumors. DESIGN AND METHODS: Retrospective analysis of 111
      patients from four institutions and a mean follow-up of 76 months. RESULTS: The
      main indications for gastroscopy were upper gastrointestinal tract symptoms. The
      mean number of lesions, maximum tumoral diameter, and percentage of cells
      expressing Ki-67 labeling index were 3.6+/-3.8, 8+/-12.1 mm and 1.9+/-2.4%
      respectively. Serum gastrin and chromogranin A (CgA) levels were elevated in
      100/101 and 85/90 patients respectively. Conventional imaging studies
      demonstrated pathology in 9/111 patients. Scintigraphy with radiolabeled
      octreotide was positive in 6/60 without revealing any additional lesions. From
      the 59 patients who had been followed-up without any intervention, five developed
      tumor progression. Thirty-two patients were treated with long-acting somatostatin
      analogs (SSAs), leading to a significant reduction of gastrin and CgA levels,
      number of visible tumors, and CgA immune-reactive tumor cells in 28, 19, 27, and
      23 treated patients respectively. Antrectomy and/or gastrectomy were initially
      performed in 20 patients and a complete response was achieved in 13 patients. The
      most common comorbidities were vitamin B12 deficiency, thyroiditis, and
      parathyroid adenomas. CONCLUSIONS: Most GCs1 are grade 1 (82.7%) tumors
      presenting with stage I (73.9%) disease with no mortality after prolonged follow
      up. Ocreoscan did not provide further information compared with conventional
      imaging techniques. Treatment with SSAs proved to be effective for the duration
      of administration.

PMID- 23132700
TI  - Pregabalin for alcohol dependence: a critical review of the literature.
AB  - INTRODUCTION: Alcohol dependence represents a severe pathological disorder
      associated with a significant rate of morbidity and mortality. To date, limited
      pharmacological agents exist to treat this disorder, and there is a growing
      interest for new therapies. In this context, pregabalin represents a promising
      strategy. Pregabalin, like gabapentin, selectively binds to the
      alpha(2)deltasubunit of voltage-gated calcium channels, inhibiting release of
      excessive levels of excitatory neurotransmitters. The main focus of this review
      is the clinical use of pregabalin in alcoholic patients, but the authors also
      reported some data about chemistry, pharmacology, and pharmacokinetics of this
      drug. METHODS: The authors conducted a PubMed search of clinical human studies
      published in English from January 2000 to August 2012 using the following search
      terms: pregabalin alcohol dependence, pregabalin alcohol withdrawal, pregabalin
      alcoholism. RESULTS: The search revealed a total of five studies: two trials for
      the treatment of alcohol relapse and three articles for the management of alcohol
      withdrawal syndrome with pregabalin. The critical review of the literature
      suggests that pregabalin could be a novel and effective treatment option for the
      management of alcohol relapse in detoxified patients, whereas until now there
      have been mixed results for the treatment of alcohol withdrawal syndrome. In
      particular, pregabalin showed a greater beneficial effect on patients with
      comorbid conditions such as alcoholism and generalized anxiety disorders. The
      exact mechanism of action of pregabalin in the management of alcoholism is not
      well understood but it is thought to be due mainly to the modulation of
      neurotransmitters such as glutamate and norepinephrine by inhibiting activity
      dependent calcium influx in nerve terminals. CONCLUSION: Pregabalin, within a
      dosage of 150-450 mg/day, showed beneficial effects for alcohol relapse
      prevention and contrasting results for the treatment of the withdrawal syndrome.
      Its use appears to be safe and well tolerated.

PMID- 23132701
TI  - Rational design of a nonbasic molecular receptor for selective NH4+/K+
      complexation in the gas phase.
AB  - A new molecular receptor (1) for ammonium recognition has been designed and
      constructed by using only carbon atoms. This molecular receptor can co-exist in
      two different isoenergetic conformations but, upon complexation, the conformers
      are no longer isoenergetic, and a basket-shaped conformation becomes clearly more
      stable. The pre-organised tetrahedral structure of this basket-shaped molecule
      favours the complexation of ammonium ions by N-H???pi interactions with the four
      phenyl groups of the host. A similar behaviour is not observed in a similar, but
      less pre-organised, reference molecule. ESI-MS competition experiments show that
      1 is able to bind NH(4)(+) over K(+) selectively. This is the first example of a
      neutral molecular receptor that shows a remarkable NH(4)(+)/K(+) selectivity. DFT
      calculations provide insight into the nature of host-guest interactions of both
      1?NH(4)(+) and 1?K(+) complexes as well as in the mechanism involved in multiple
      cation-pi interactions and the influence of these interactions on the
      conformational stability and the selective binding of the host.

PMID- 23132702
TI  - Impact of oncology-related direct-to-consumer advertising: association with
      appropriate and inappropriate prescriptions.
AB  - BACKGROUND: Little is known about the impact of direct-to-consumer advertising
      (DTCA) on appropriate versus inappropriate prescribing. Aromatase inhibitor (AI)
      therapy for breast cancer provides an ideal paradigm for studying this issue,
      because AIs have been the focus of substantial DTCA, and because they should only
      be used in postmenopausal women, age can serve as a simple surrogate marker of
      appropriateness. METHODS: Data regarding national DTCA spending for the AIs were
      obtained from TNS Multimedia; hormonal therapy prescription data were obtained
      from IMS Health. Time series analyses were performed to characterize the
      association between monthly changes in DTCA spending for the AIs and monthly
      changes in the proportion of all new hormonal therapy prescriptions represented
      by the AIs from October 2005 to September 2007. Analyses were stratified by age,
      considering prescriptions for women <= 40 (likely premenopausal) to be
      inappropriate and those for women > 60 (likely postmenopausal) to be appropriate.
      RESULTS: Monthly dollars spent on AI-associated DTCA varied considerably
      ($118,600 to $22,019,660). Time series analysis revealed that for every million
      dollars spent on DTCA for the AIs, there was an associated increase 3 months
      later in the new AI prescription proportion of 0.15% for all ages (P < .0001) and
      0.18% for those > 60 years (P < .0001), but no significant change for those <= 40
      at any time from 0 to 6 months. CONCLUSIONS: DTCA for the AIs was associated with
      increases in appropriate prescriptions with no significant effect on
      inappropriate prescriptions, suggesting that DTCA may not foster inappropriate
      medication use for certain drug classes.

PMID- 23132703
TI  - Controlled deprotection and reorganization of uranyl oxo groups in a binuclear
      macrocyclic environment.
AB  - Switching on uranium(V) reactivity: The silylated uranium(V) dioxo complex
      [(Me(3)SiOUO)(2)(L)(2)] (A) is inert to oxidation, but after two-electron
      reduction to [(Me(3)SiOUO)(2)(L)](2-) (1), it can be desilylated to form [OU(MU
      O)(2)UO(L)(2)](2-) (2) with reinstated uranyl character. Removal of the silyl
      group uncovers new redox and oxo rearrangement chemistry for uranium, thus
      reforming the uranyl motif and involving the U(VI/V) couple in dioxygen
      reduction.

PMID- 23132704
TI  - Letter to the editor: do we need to re-think the 10/66 dementia study for Africa.

PMID- 23132706
TI  - Antithyroid antibodies, cognition and instrumental activities of daily living in
      the elderly.

PMID- 23132707
TI  - Relationship of 2D:4D finger ratio with androgen receptor CAG and GGN repeat
      polymorphism.
AB  - OBJECTIVES: The relative length of the second-to-fourth digits (2D:4D) has been
      linked with prenatal androgen in humans. A recent study shows that the 2D:4D
      ratio in mice is controlled by the balance of androgen to estrogen signaling
      during a narrow window of digit development. Androgen receptor (AR) activity is
      higher in digit 4 than in digit 2, and inactivation of AR decreases growth of
      digit 4, which causes a higher 2D:4D ratio. At the molecular level, the effect of
      androgens is mediated through the activation of AR. The CAG/GGN repeat
      polymorphisms of the AR gene are associated with AR activity. Here, we
      investigate the effect of CAG/GGN repeat polymorphisms in AR on 2D:4D in Chinese.
      METHODS: Digit lengths of the second and fourth fingers were measured from
      photocopies of the ventral surface of the hand and by actual finger measurements.
      We genotyped AR polymorphisms by ABI 3730 DNA analyzer. RESULTS: We found that
      left hand 2D:4D ratio was longer than that of the right hand both in males and in
      females. We failed to find any relationship between CAG / GGN alleles and the
      left hand, right hand, right minus left-hand or mean hand 2D:4D ratios (all, r <
      0.20, P > 0.05). CONCLUSIONS: In this study, we first found that the left hand
      2D:4D ratio was longer than that of the right hand in both males and females.
      However, we found that both CAG and GGN alleles were not associated with the left
      hand, right hand, right minus left-hand or mean hand 2D:4D ratios.

PMID- 23132708
TI  - Transumbilical sleeve gastrectomy with an accessory lateral port: surgical
      results in 237 patients and 1-year follow-up.
AB  - BACKGROUND: The transumbilical approach has recently been shown to be safe for
      several surgical procedures. Case series of sleeve gastrectomy (SG) with a
      transumbilical approach (TUSG) has been reported with various techniques. The
      objective of this report is to present the technique, surgical results, and 1
      year follow-up results of simplified TUSG using rigid instruments. METHODS: All
      of the patients who had undergone SG since July 2010 were offered a
      transumbilical approach. The operative technique involves a transumbilical
      incision and the introduction of a SILS(r) or GelPoint(r) multiport and a 5-mm
      metallic accessory trocar laterally in the left flank. Rigid instruments were
      used in all patients. Gastric transection was made 4-5 cm proximal to the
      pylorus, calibrated with a 36-Fr bougie. Selected hemostasis to the staple line
      was achieved with metallic clips. RESULTS: A total of 237 patients underwent
      TUSG. Patient body mass index ranged from 30 to 46 kg/m(2). The mean operative
      time was 49.5 +/- 14.9 min. Six patients presented with early complications,
      including hemoperitoneum in three cases, antral leak in one case, intestinal
      perforation in one case, and portal vein thrombosis in one case. Conversion to
      the multitrocar technique was required in one patient. There were no mortalities.
      The mean length of hospital stay was 2.2 +/- 1 days. The cosmetic result was
      satisfactory for all of the patients. CONCLUSIONS: TUSG is a safe and feasible
      procedure using the described technique. The insertion of a 5-mm assistance
      trocar simplifies the procedure, allowing the use of rigid instruments.

PMID- 23132709
TI  - Heterozygosity assessment of five STR loci located at 5q13 region for
      preimplantation genetic diagnosis of spinal muscular atrophy.
AB  - Preimplantation genetic diagnosis (PGD) has been considered as an alternative to
      prenatal diagnosis for prevention of genetic disorders while avoiding the
      subsequent termination of pregnancy. However, the limited amount of template DNA
      available in a single diploid cell used for PGD leads to number of problems
      including an increased incidence of detectable contamination; amplification
      failure and allele drop out. Due to their highly polymorphic and amplifiable
      characteristics, short tandem repeat (STR) analysis has been proposed as a mean
      to overcome these limitations. Heterozygosity of the applied STRs is of paramount
      importance in their informativity, and should therefore be studied in any certain
      population. Here, for the first time, we report on the heterozygosity analysis of
      five STR markers (D5S1408, D5S1417, D5S610, D5S629 and D5S637) flanking to SMA
      gene region, to examine their applicability in the PGD for SMA disease. We have
      also investigated other statistical features of these markers and found that all
      of the five studied STRs were informative and four meet the Hardy-Weinberg
      equilibrium for the studied population. Furthermore, our results propose that
      similar approaches can be used for the PGD of other single gene disorders.

PMID- 23132710
TI  - The polymorphisms of LYRM1 gene and their association with body measurement and
      ultrasound traits of Qinchuan cattle.
AB  - Body measurement and meat quality traits which play important roles in the
      assessment of productivity and economy in cattle were influenced by genes and
      environmental factors. Latest studies showed that LYR motif containing 1 (LYRM1)
      may be involved in influencing fatness deposition in animals. The objective of
      this study was to detect bovine LYRM1 gene polymorphism and analyze its
      association with body measurement and meat quality traits of cattle. Blood
      samples were taken from a total of 404 Qinchuan cattle aged from 18-24 months.
      Created restriction site-polymerase chain reaction-restriction fragment length
      polymorphism (CRS-PCR-RFLP) and DNA sequencing were used to find out LYRM1 single
      polymorphism nucleotide (SNPs). Sequence analysis of LYRM1 gene revealed two SNPs
      (g.165 C > A, g.193 A > G) in 3' untranslated region (3'UTR) of exon 3. And g.165
      C > A showed two genotypes namely AC and CC while g.193 A > G showed three
      genotypes: AA, AG and GG. Analysis results showed that there were significant
      associations between polymorphism of these two and body measurement and meat
      quality traits in Qinchuan cattle population. Based on the results obtained from
      this study, it is inferred that LYRM1 gene may have potential effects on body
      measurement and meat quality traits in Qinchuan cattle population and could be
      used for marker-assisted selection.

PMID- 23132711
TI  - Free-radical oxidation of plasma fibrin-stabilizing factor.

PMID- 23132712
TI  - Alteration of hormonal sensitivity of adenylyl cyclase in the brain of rats with
      prolonged streptozotocin diabetes.

PMID- 23132713
TI  - The combination of moisture deficit, moderate cooling, and melafen changes the
      morphology of mitochondria in pea seedling.

PMID- 23132714
TI  - Molecular dynamics and free energy of binding of oleic acid to DNA in aqueous
      solutions.

PMID- 23132715
TI  - Alkylhydroxybenzenes modify immune complex size.

PMID- 23132716
TI  - The role of D1 like receptors in the regulation of juvenile hormone synthesis in
      Drosophila females with increased dopamine level.

PMID- 23132717
TI  - Study of efficiency of the modular nanotransporter for targeted delivery of
      photosensitizers to melanoma cell nuclei in vivo.

PMID- 23132718
TI  - Micellar catalytic effect as a factor of lipase activity regulation.

PMID- 23132719
TI  - Conical intersection participation in femtosecond dynamics of visual pigment
      rhodopsin chromophore cis-trans photoisomerization.

PMID- 23132720
TI  - Biologically active clathrates amiloiodin and amilopektoiodin under exposure to
      low-frequency acoustic field.

PMID- 23132721
TI  - Dimebon activates autophagosome components in human neuroblastoma SH-SY5Y cells.

PMID- 23132722
TI  - Antimutagens (beta-purothionin and crown compound) as modulators of expression of
      genes involved in carcinogenesis in human cells.

PMID- 23132723
TI  - Candidate mucosal vaccine against hepatitis B based on tomatoes transgenic for
      the preS2-S gene.

PMID- 23132724
TI  - Low-intensity laser radiation changes amino acid composition of wheat callus
      tissues.

PMID- 23132725
TI  - Dopamine effect on 20-hydroxyecdysone level is mediated by juvenile hormone in
      Drosophila females.

PMID- 23132726
TI  - Narcissistic versus social self-sorting of oligophenyleneethynylene derivatives:
      from isodesmic self-assembly to cooperative co-assembly.
AB  - Narcissistic versus social! The self-assembly of two structurally related
      oligophenyleneethynylene derivatives featuring polar or nonpolar peripheral
      chains is reported. Their remarkable narcissistic versus social self-sorting
      behaviour in aqueous media can be controlled by concentration and solvent
      changes.

PMID- 23132727
TI  - The use of sensory attributes, sugar content, instrumental data and consumer
      acceptability in selection of sweet potato varieties.
AB  - BACKGROUND: As eating quality is important for adoption of new varieties, nine
      orange-fleshed and three cream-fleshed sweet potato varieties were assessed for
      sensory characteristics, dry mass and free sugar content, instrumental texture
      and colour and consumer acceptability (n =  216) in a peri-urban South African
      setting. RESULTS: Cream-fleshed varieties were higher in yellow-green colour and
      sweet potato-like flavour and lower in graininess. Orange-fleshed varieties were
      higher in pumpkin-like flavour, orange colour, discolouration and sucrose
      content. Partial least squares regression analysis showed that the most accepted
      varieties (Impilo, Excel, Resisto, 2001_5_2, Serolane, W-119 and Monate) were
      associated with sweet flavour, dry mass and maltose content, while the least
      accepted varieties (Beauregard, Khano and 1999_1_7) were associated with
      wateriness. Pearson correlation analysis highlighted correlations of sensory
      attributes yellow and orange with instrumental colour measurements (colour a* and
      colour b*), instrumental firmness with sensory firmness, dry mass with sensory
      wateriness, and maltose content with sensory sweet and sweet potato-like flavour.
      The varieties were clustered into three groups. Consumer acceptability for eating
      quality correlated with maltose content, dry mass and sweet flavour. CONCLUSION:
      Chemical and instrumental measurements were identified to evaluate key attributes
      and will be useful in the intermediate phases of sweet potato varietal
      development.

PMID- 23132728
TI  - Emerging viral diseases in kidney transplant recipients.
AB  - Viruses are the most important cause of infections and a major source of
      mortality in Kidney Transplant Recipients (KTRs). These patients may acquire
      viral infections through exogenous routes including community exposure, donor
      organs, and blood products or by endogenous reactivation of latent viruses.
      Beside major opportunistic infections due to CMV and EBV and viral hepatitis B
      and C, several viral diseases have recently emerged in KTRs. New medical
      practices or technologies, implementation of new diagnostic tools, and improved
      medical information have contributed to the emergence of these viral diseases in
      this special population. The purpose of this review is to summarize the current
      knowledge on emerging viral diseases and newly discovered viruses in KTRs over
      the last two decades. We identified viruses in the field of KT that had shown the
      greatest increase in numbers of citations in the NCBI PubMed database. BKV was
      the most cited in the literature and linked to an emerging disease that
      represents a great clinical concern in KTRs. HHV-8, PVB19, WNV, JCV, H1N1
      influenza virus A, HEV, and GB virus were the main other emerging viruses.
      Excluding HHV8, newly discovered viruses have been infrequently linked to
      clinical diseases in KTRs. Nonetheless, pathogenicity can emerge long after the
      discovery of the causative agent, as has been the case for BKV. Overall,
      antiviral treatments are very limited, and reducing immunosuppressive therapy
      remains the cornerstone of management.

PMID- 23132729
TI  - Epigenetic silencing of Id4 identifies a glioblastoma subgroup with a better
      prognosis as a consequence of an inhibition of angiogenesis.
AB  - BACKGROUND: Inhibitors of DNA binding/differentiation (Id1 to Id4) are a family
      of helix-loop-helix transcription factors, which are highly expressed during
      embryogenesis and at lower levels in mature tissues. Id4 plays an important role
      in neuronal stem cell differentiation, and its deregulation has been implicated
      in glial neoplasia. METHODS: The methylation status of Id4 was analyzed by
      methylation-specific polymerase chain reaction (PCR) in 62 glioblastoma (GBM)
      cases and in 20 normal brain tissues. Methylation status of Id4 was confirmed by
      sequencing after subcloning and messenger RNA (mRNA) and protein expression. We
      also evaluated the mRNA expression of MGP (matrix GLA protein), TGF-beta1
      (transforming growth factor beta 1), and VEGF (vascular endothelial growth
      factor) by real-time PCR analysis. Clinical and histological assessment of tumor
      angiogenesis was performed by evaluating the relative enhancing tumor ratio on
      magnetic resonance imaging and microvessel density on von Willebrand factor
      stained sections, respectively. RESULTS: The promoter of Id4 was methylated in 23
      of 62 (37%) GBMs. In methylated GBMs, Id4 mRNA was significantly reduced,
      compared with unmethylated GBMs (P = .0002). A significant reduction of protein
      expression was detected in all hypermethylated cases. GBMs with methylated Id4
      showed a significant reduction of MGP, TGF-beta1, and VEGF mRNA expression and
      had significantly lower relative enhancing tumor ratio (P = .0108) and
      microvessel density (P = .0241) values with respect to unmethylated GBMs.
      Finally, Id4 methylation was significantly associated with a favorable clinical
      outcome (P = .0006). CONCLUSIONS: These data suggest that methylation of Id4 may
      be involved in the pathogenesis of GBM and in the resistance of this neoplasm to
      conventional treatment throughout MGP-mediated neoangiogenesis.

PMID- 23132730
TI  - Late presentation of anal canal duplication in an adolescent female--a rare
      diagnosis.

PMID- 23132731
TI  - The splicing factor SRSF6 is amplified and is an oncoprotein in lung and colon
      cancers.
AB  - An increasing body of evidence connects alterations in the process of alternative
      splicing with cancer development and progression. However, a direct role of
      splicing factors as drivers of cancer development is mostly unknown. We analysed
      the gene copy number of several splicing factors in colon and lung tumours, and
      found that the gene encoding for the splicing factor SRSF6 is amplified and over
      expressed in these cancers. Moreover, over-expression of SRSF6 in immortal lung
      epithelial cells enhanced proliferation, protected them from chemotherapy-induced
      cell death and converted them to be tumourigenic in mice. In contrast, knock-down
      of SRSF6 in lung and colon cancer cell lines inhibited their tumourigenic
      abilities. SRSF6 up- or down-regulation altered the splicing of several tumour
      suppressors and oncogenes to generate the oncogenic isoforms and reduce the
      tumour-suppressive isoforms. Our data suggest that the splicing factor SRSF6 is
      an oncoprotein that regulates the proliferation and survival of lung and colon
      cancer cells.

PMID- 23132732
TI  - Evaluation of a standardized humor group in a clinical setting: a feasibility
      study for older patients with depression.
AB  - BACKGROUND: Positive effects of humor on older patients with depressive symptoms
      have been repeatedly reported. Empirical evidence however is rare. We
      investigated the efficacy of a standardized humor therapy group in a clinical
      context especially for older depressed patients. PATIENTS AND METHODS: An
      experimental group with treatment (49 patients) was compared with a control group
      with no treatment (50 patients) in a semi-randomized design. Included were
      patients with major depression according to ICD-10. A set of questionnaires
      (Geriatric Depression Scale, Short Form Health Survey, State-Trait-Cheerfulness
      Inventory, and Satisfaction with Life Scale) was administered pretreatment and
      posttreatment. RESULTS: Both groups showed improvement for depression, suicidal
      tendency, state cheerfulness, and state bad mood. Only participants of the humor
      group showed changes of state seriousness and satisfaction with life (p < 0.05).
      Further trends could be demonstrated for higher changes in state cheerfulness and
      resilience for the humor group. CONCLUSION: Our results indicate an additional
      benefit of this specific therapeutic intervention for older depressed patients.

PMID- 23132733
TI  - Mixed proton-electron conducting chromite electrocatalysts as anode materials for
      LWO-based solid oxide fuel cells.

PMID- 23132734
TI  - Structure-based mutational study of an archaeal DNA ligase towards improvement of
      ligation activity.
AB  - DNA ligases catalyze the joining of strand breaks in duplex DNA. The DNA ligase
      of Pyrococcus furiosus (PfuLig), which architecturally resembles the human DNA
      ligase I (hLigI), comprises an N-terminal DNA-binding domain, a middle
      adenylylation domain, and a C-terminal oligonucleotide-binding (OB)-fold domain.
      Here we addressed the C-terminal helix in the OB-fold domain of PfuLig by
      mutational analysis. The crystal structure of PfuLig revealed that this helix
      stabilizes a closed conformation of the enzyme by forming several ionic
      interactions with the adenylylation domain. The C-terminal helix is oriented
      differently in hLigI when DNA is bound; this suggested that disruption of its
      interaction with the adenylylation domain might facilitate the binding of DNA
      substrates. We indeed identified one of its residues, Asp540, as being critical
      for ligation efficiency. The D540R mutation improved the overall ligation
      activity relative to the wild-type enzyme, and at lower temperatures; this is
      relevant to applications such as ligation amplification reactions. Physical and
      biochemical analyses indicated that the improved ligation activity of the D540R
      variant arises from effects on the ligase adenylylation step and on substrate DNA
      binding in particular.

PMID- 23132735
TI  - Neutrophils recruited by CXCR1/2 signalling mediate post-incisional pain.
AB  - BACKGROUND: Neutrophil recruitment mediated by the CXCL1/KC chemokine and its
      receptors CXCR1/CXCR2 plays a critical role in inflammatory diseases. Recently,
      neutrophil migration and activation triggered by CXCL1-CXCR1/2 signalling was
      implicated in inflammatory nociception; however, their role in post-surgical pain
      has not been elucidated. In this study, we addressed the function of neutrophils
      in the genesis of post-incisional pain in an experimental model of post-surgical
      pain. METHODS: Mechanical hyperalgesia was determined with an electronic von Frey
      test in a mouse hindpaw incisional model. Neutrophil accumulation and the level
      of CXCL1/KC in the plantar tissue were determined by myeloperoxidase activity
      assay and enzyme-linked immunosorbent assay, respectively. RESULTS: An incision
      in the mouse hindpaw produces long-lasting mechanical hyperalgesia that persists
      for at least 72 h after surgery. Following surgery, there was an increase in both
      neutrophil accumulation and the CXCL1/KC level in the incised paws. The depletion
      of the mouse neutrophils by vinblastine sulphate or anti-neutrophil antibody
      treatments reduced the mechanical hyperalgesia after paw incision. Furthermore,
      the treatment of mice with ladarixin, an orally acting CXCR1/2 antagonist, also
      reduced both the mechanical hyperalgesia and the infiltration of neutrophils in
      the incised paws. CONCLUSION: In conclusion, it appears that after surgical
      processes, neutrophils are recruited by CXCL1-CXCR1/2 signalling and participate
      in the cascade of events, leading to mechanical hyperalgesia. These results
      suggest that blocking neutrophil migration through the inhibition of CXCL1
      CXCR1/2 signalling might be a target to control post-surgical pain.

PMID- 23132736
TI  - Prognostic significance of vascular endothelial growth factor gene polymorphisms
      in patients with colorectal cancer.
AB  - BACKGROUND: Angiogenesis plays an important role in tumor development,
      progression, and metastasis. Vascular endothelial growth factor (VEGF) is a key
      regulator of angiogenesis. However, the contribution of common VEGF polymorphisms
      to colorectal cancer (CRC) prognosis remains unclear. METHODS: We have genotyped
      four polymorphisms of VEGF (-2578C>A, -1154G>A, -634G>C, and 936C>T) in 350 CRC
      cases from the Korean population. The genotyping of VEGF polymorphisms was
      performed by polymerase chain reaction-restriction fragment length polymorphism
      assay. RESULTS: Although not every VEGF polymorphism was significantly correlated
      with patient prognosis in overall 350 CRC patients, we found that the VEGF 
      2578CA genotype was associated with a significantly poor prognosis for rectal
      cancers compared to the CC genotype (HR = 2.156; 95 % CI 1.090-4.267; P = 0.028).
      In addition, we found that the -2578A/-1154G/-634G/+936C haplotype was
      significantly associated with a decreased overall survival (OS) rate in all 350
      CRC patients (HR = 2.530; 95 % CI 1.340-4.780; P = 0.004). In combination
      analysis, we found that the combined VEGF -2578CA+AA/-1154GG genotype was
      associated with a poor OS rate in all 350 CRC patients (HR = 2.068; 95 % CI 1.159
      3.693; P = 0.015). CONCLUSIONS: The VEGF gene polymorphisms investigated in this
      study were not found to be independent prognostic markers in Korean CRC
      populations. However, our results suggest that the VEGF -2578C>A variant may be a
      potential genetic marker for rectal cancer prognosis. Further large population
      studies are warranted to define whether the -2578C>A polymorphism is a prognostic
      marker of rectal cancer.

PMID- 23132737
TI  - Next frontiers in the genetic epidemiology of Alzheimer's disease.

PMID- 23132738
TI  - Current status of myocardial regeneration therapy.
AB  - Myocardial regeneration therapy has emerged as an alternative therapy for heart
      failure and is expected to replace current conventional therapies. As a cell
      source, the presence of resident cardiac stem cells (RCSC) in the heart has been
      reported by many researchers. These RCSC show multi-potency and are considered to
      differentiate into myocytes. On the other hand, bone marrow stem cells have
      received the greatest attention as a source of cell transplantation therapy in
      the current era, with a larger number of clinical applications reported because
      of their ease and safety. Myoblasts have also emerged as a possible cell source
      for clinical applications. We previously found that myoblast-cell-sheet
      implantation improved cardiac function and ventricle thickness in a rat MI model.
      Furthermore, we conducted a pre-clinical large animal study using porcine MI and
      dog DCM models, and confirmed the effectiveness of skeletal myoblast sheets.
      Thereafter, we conducted clinical applications of skeletal myoblast implantation.
      It may eventually be possible to perform regeneration therapy as a routine
      therapeutic method.

PMID- 23132739
TI  - Numb/Notch signaling plays an important role in cerebral ischemia-induced
      apoptosis.
AB  - Numb has been shown to play diverse roles in the central nervous system of adult
      mammals, and accumulating evidence indicates a role for Numb in apoptosis. In
      this study, we characterize the role of Numb in ischemia-induced apoptosis, and
      investigate the underlying pathway involved in this process. In vivo, exposure of
      pheochromocytoma (PC12) cells to glucose deprivation (GD) resulted in caspase-3
      dependent apoptosis. Numb expression was upregulated by GD in a time-dependent
      manner, while Notch expression was down regulated. Knocking down endogenous Numb
      expression via siRNA protected PC12 cells from GD-induced apoptosis, whereas Numb
      overexpression sensitized PC12 cells to GD-induced apoptosis. In vivo,
      significantly increased Numb expression levels, together with activation of
      apoptosis, can be observed in the ischemic penumbra following cerebral ischemia.
      Taken together, our data show that Numb promotes ischemia-induced apoptosis.
      Based on these results, we conclude that inhibition of Numb could be a novel
      therapeutic approach for inhibiting apoptosis in the ischemic penumbra.

PMID- 23132741
TI  - Drop the BMJ paper edition entirely.

PMID- 23132740
TI  - Isolation stress exposure and consumption of palatable diet during the
      prepubertal period leads to cellular changes in the hippocampus.
AB  - Social isolation is one of the most potent stressors in the prepubertal period
      and may influence disease susceptibility or resilience in adulthood. The
      glucocorticoid response and, consequently, the adaptive response to stress
      involve important changes in mitochondrial functions and apoptotic signaling.
      Previous studies have shown that consumption of a palatable diet reduces some
      stress effects. Therefore, the aim of the present study was to investigate
      whether isolation stress in early life can lead to cellular alterations in the
      hippocampus. For this, we evaluated oxidative stress parameters, DNA breakage
      index, mitochondrial mass and potential, respiratory chain enzyme activities,
      apoptosis, and necrosis in the hippocampus of juvenile male rats submitted or not
      to isolation stress during the pre-puberty period. We also verified whether
      consumption of a palatable diet during this period can modify stress effects.
      Results show that stress led to an oxidative imbalance, DNA breaks, increased the
      mitochondrial potential and early apoptosis, and decreased the number of live and
      necrotic cells. In addition, the palatable diet increased glutathione peroxidase
      activity, high mitochondrial potential and complex I-III activity in the
      hippocampus of juvenile rats. The administration of a palatable diet during the
      isolation period prevented the stress effects that caused the reduction in live
      cells and increased apoptosis. In conclusion, the stress experienced during the
      pre-pubertal period induced a hippocampal oxidative imbalance, DNA damage,
      mitochondrial dysfunction, and increased apoptosis, while consumption of a
      palatable diet attenuated some of these effects of exposure, such as the
      reduction in live cells and increased apoptosis, besides favoring an increase in
      antioxidant enzymes activities.

PMID- 23132742
TI  - p-tert-Butylcalix[8]arene: an extremely versatile platform for cluster formation.
AB  - p-tert-Butylcalix[4]arene is a bowl-shaped molecule capable of forming a range of
      polynuclear metal clusters under different experimental conditions. p-tert
      Butylcalix[8]arene (TBC[8]) is a significantly more flexible analogue that has
      previously been shown to form mono- and binuclear lanthanide (Ln) metal
      complexes. The latter (cluster) motif is commonly observed and involves the
      calixarene adopting a near double-cone conformation, features of which suggested
      that it may be exploited as a type of assembly node in the formation of larger
      polynuclear lanthanide clusters. Variation in the experimental conditions
      employed for this system provides access to Ln(1), Ln(2), Ln(4), Ln(5), Ln(6),
      Ln(7) and Ln(8) complexes, with all polymetallic clusters containing the common
      binuclear lanthanide fragment. Closer inspection of the structures of the
      polymetallic clusters reveals that all but one (Ln(8)) are in fact based on metal
      octahedra or the building blocks of octahedra, with the identity and size of the
      final product dependent upon the basicity of the solution and the deprotonation
      level of the TBC[8] ligand. This demonstrates both the versatility of the ligand
      towards incorporation of additional metal centres, and the associated
      implications for tailoring the magnetic properties of the resulting assemblies in
      which lanthanide centres may be interchanged.

PMID- 23132744
TI  - Intercellular communication within the rat anterior pituitary gland. XV.
      Properties of spontaneous and LHRH-induced Ca2+ transients in the transitional
      zone of the rat anterior pituitary in situ.
AB  - In the transitional zone of the rat anterior pituitary, spontaneous and LHRH
      induced Ca(2+) dynamics were visualized using fluo-4 fluorescence Ca(2+) imaging.
      A majority of cells exhibited spontaneous Ca(2+) transients, while small
      populations of cells remained quiescent. Approximately 70% of spontaneously
      active cells generated fast, oscillatory Ca(2+) transients that were inhibited by
      cyclopiazonic acid (10 MUm) but not nicardipine (1 MUm), suggesting that Ca(2+)
      handling by endoplasmic reticulum, but not Ca(2+) influx through voltage
      dependent L-type Ca(2+) channels, plays a fundamental role in their generation.
      In the adult rat anterior pituitary, LHRH (100 MUg/ml) caused a transient
      increase in the Ca(2+) level in a majority of preparations taken from the morning
      group rats killed between 0930 h and 1030 h. However, the second application of
      LHRH invariably failed to elevate Ca(2+) levels, suggesting that the long-lasting
      refractoriness to LHRH stimulation was developed upon the first challenge of
      LHRH. In contrast, LHRH had no effect in most preparations taken from the
      afternoon group rats euthanized between 1200 h and 1400 h. In the neonatal rat
      anterior pituitary, LHRH caused a suppression of spontaneous Ca(2+) transients.
      Strikingly, the second application of LHRH was capable of reproducing the
      suppression of Ca(2+) signals, indicating that the refractoriness to LHRH had not
      been established in neonatal rats. These results suggest that responsiveness to
      LHRH has a long-term refractoriness in adult rats, and that the physiological
      LHRH surge may be clocked in the morning. Moreover, LHRH-induced excitation and
      associated refractoriness appear to be incomplete in neonatal rats and may be
      acquired during development.

PMID- 23132743
TI  - Ligand-dependent actions of the vitamin D receptor are required for activation of
      TGF-beta signaling during the inflammatory response to cutaneous injury.
AB  - The vitamin D receptor (VDR) has both 1,25-dihydroxyvitamin D-dependent and 
      independent actions in the epidermis. Ligand-dependent actions of the VDR have
      been shown to promote keratinocyte differentiation and to regulate formation of
      the epidermal barrier. In contrast, the actions of the VDR that regulate
      postmorphogenic hair cycling do not require 1,25-dihydroxyvitamin D. The VDR also
      has immunomodulatory actions that are dependent on its ligand, 1,25
      dihydroxyvitamin D. To determine whether the ligand-dependent or -independent
      actions of the VDR regulate the inflammatory response to cutaneous injury,
      studies were performed in control, VDR knockout, and vitamin D-deficient mice.
      These investigations demonstrate that absence of receptor or ligand impairs the
      dermal response to cutaneous injury. Although neutrophil recruitment is not
      affected, the absence of VDR signaling leads to defects in macrophage recruitment
      and granulation tissue formation. Studies performed to identify the molecular
      basis for this phenotype demonstrate that absence of the VDR, or its ligand,
      impairs TGF-beta signaling in the dermis, characterized by decreased expression
      of monocyte chemotactic protein-1 and reduced phosphorylation of phosphorylated
      Smad-3 as well as attenuated phosphorylated Smad-3 phosphorylation in response to
      TGF-beta in primary dermal fibroblasts lacking the VDR. Thus, these data
      demonstrate that the liganded VDR interacts with the TGF-beta signaling pathway
      to promote the normal inflammatory response to cutaneous injury.

PMID- 23132745
TI  - [Use of cardiac MRI in the field of electrophysiology. Present status and future
      aspects].
AB  - In recent years, ablation therapy has become the first-line treatment of modern
      electrophysiology in patients with cardiac arrhythmias. Today, cardiac magnetic
      resonance imaging (cMRI) is an important supportive imaging technique in the
      implementation of complex electrophysiological investigations and ablation
      therapy. In clinical routine, cMRI is used not only to generate accurate three
      dimensional (3D) models of cavities of the heart but also for visualization of
      complex anatomical structures. The development of cMRI makes it possible to
      detect the underlying substrate of complex arrhythmias such as myocardial scar in
      patients with ventricular tachycardia or the structural remodeling of the left
      atrium in patients with atrial fibrillation. The opportunity of fusion of the
      different imaging modalities (e.g., fluoroscopy, cMRI) has become essential for
      the planning and the implementation of a safe ablation therapy. The possibility
      of direct visualization of induced lesions using cMRI after and in the long term
      after ablation can predict the success of therapy and detects potential
      complications. The continuous research in the field of cMRI and the development
      of MRI-compatible pacing and ablation catheters provided the basics for
      performing electrophysiological treatment in humans directly inside the MRI. The
      implementation of ablation using exact visualization of the anatomical substrate,
      precise catheter navigation and real-time visualization of lesions in cMRI
      promises to improve success rates and the safety of complex ablation treatment
      and may revolutionize electrophysiology in the future.

PMID- 23132746
TI  - Diffusion Tensor Estimation by Maximizing Rician Likelihood.
AB  - Diffusion tensor imaging (DTI) is widely used to characterize white matter in
      health and disease. Previous approaches to the estimation of diffusion tensors
      have either been statistically suboptimal or have used Gaussian approximations of
      the underlying noise structure, which is Rician in reality. This can cause
      quantities derived from these tensors - e.g., fractional anisotropy and apparent
      diffusion coefficient - to diverge from their true values, potentially leading to
      artifactual changes that confound clinically significant ones. This paper
      presents a novel maximum likelihood approach to tensor estimation, denoted
      Diffusion Tensor Estimation by Maximizing Rician Likelihood (DTEMRL). In contrast
      to previous approaches, DTEMRL considers the joint distribution of all observed
      data in the context of an augmented tensor model to account for variable levels
      of Rician noise. To improve numeric stability and prevent non-physical solutions,
      DTEMRL incorporates a robust characterization of positive definite tensors and a
      new estimator of underlying noise variance. In simulated and clinical data, mean
      squared error metrics show consistent and significant improvements from low
      clinical SNR to high SNR. DTEMRL may be readily supplemented with spatial
      regularization or a priori tensor distributions for Bayesian tensor estimation.

PMID- 23132747
TI  - Predictors of anxiety and depression in hematopoietic stem cell transplant
      patients during protective isolation.
AB  - OBJECTIVE: To examine in a sample of hematopoietic stem cell transplant patients
      assessed throughout protective isolation (i) levels of anxiety and depression and
      (ii) pre-isolation factors (socio-demographics, biomedical variables and
      personality traits), which might predict higher levels of anxiety and depression
      during isolation. METHODS: The study used a longitudinal prospective design.
      Anxiety and depression were assessed in 107 participants by the State-Trait
      Anxiety Inventory and Self-rating Depression Scale at admission and weekly at
      fixed time points throughout isolation. Among pre-isolation factors, patients'
      psychological status was evaluated by the Cognitive Behavioral Assessment (2.0).
      Predictors were explored by random-effects models. RESULTS: One-tenth of the
      patients suffered from clinically significant anxiety and depressive symptoms at
      admission. Although the percentage of depressed patients increased more than
      twofold after 2 weeks of isolation, that of anxious patients did not
      significantly change over time. Female gender, higher anxiety and obsessive
      compulsive symptoms, intratensive personality traits and lower performance status
      predicted higher depression during isolation. CONCLUSIONS: Anxiety and depression
      represent a relevant problem for hematopoietic stem cell transplant patients
      during isolation. Early detection of predictors, such as anxiety levels,
      obsessive-compulsive symptoms and performance status, could help prevent
      depression via targeted psychological intervention.

PMID- 23132748
TI  - Synthesis of glycopolymers by controlled radical polymerization techniques and
      their applications.
AB  - Natural saccharides are involved in numerous biological processes. It has been
      shown that these carbohydrates play a role in cell adhesion and proliferation, as
      well as protein stabilization, organization, and recognition. Certain
      carbohydrates also serve as receptors for viruses and bacteria. They are over
      expressed in diseases such as cancer. Hence, a lot of effort has been focused on
      mimicking these sugars. Polymers with pendent saccharide groups, also known as
      glycopolymers, are studied as oligo- and polysaccharide mimics. Controlled
      radical polymerization (CRP) techniques such as atom transfer radical
      polymerization (ATRP), reversible addition-fragmentation chain transfer (RAFT)
      polymerization, and nitroxide-mediated polymerization (NMP), as well as cyanoxyl
      mediated free radical polymerization have allowed chemists to synthesize well
      defined glycopolymers that, in some cases, have particular end-group
      functionalities. This review focuses on the synthesis of glycopolymers by these
      methods and the applications of glycopolymers as natural saccharide mimics.

PMID- 23132750
TI  - Quantitative IR readout of fulgimide monolayer switching on Si(111) surfaces.
AB  - Creating photoactive monolayers of photochromes is of considerable technological
      interest. This paper describes the construct of fulgimide monolayers on silicon
      surfaces and presents a quantitative IR analysis studies of their composition and
      switching properties. The scheme on top shows the structure of the starting C
      form terminated Si(111) surface and the graph below sketches the surface
      composition at the photostationnary states under visisble and UV irradiation, as
      derived from in situ IR spectroscopy after several UV/vis irradiation cycles.

PMID- 23132749
TI  - Egr-1: new conductor for the tissue repair orchestra directs harmony
      (regeneration) or cacophony (fibrosis).
AB  - Fibroblasts and myofibroblasts are the key effector cells executing physiological
      tissue repair leading to regeneration on the one hand, and pathological
      fibrogenesis leading to chronic fibrosing conditions on the other. Recent studies
      identify the multifunctional transcription factor early growth response-1(Egr-1)
      as an important mediator of fibroblast activation triggered by diverse stimuli.
      Egr-1 has potent stimulatory effects on fibrotic gene expression, and aberrant
      Egr-1 expression or function is associated with animal models of fibrosis and
      human fibrotic disorders, including emphysema, pulmonary fibrosis, pulmonary
      hypertension and systemic sclerosis. Pharmacological suppression or genetic
      targeting of Egr-1 blocks fibrotic responses in vitro and ameliorates
      experimental fibrosis in the skin and lung. In contrast, Egr-1 appears to act as
      a negative regulator of hepatic fibrosis in mouse models, suggesting a context
      dependent role in fibrosis. The Egr-1-binding protein Nab2 is an endogenous
      inhibitor of Egr-1-mediated signalling and abrogates the stimulation of fibrotic
      responses induced by transforming growth factor-beta (TGFbeta). Moreover, mice
      deficient in Nab2 show excessive collagen accumulation in the skin. These
      observations highlight a previously unsuspected fundamental physiological
      function for the Egr-1-Nab2 signalling axis in regulating fibrogenesis, and
      suggest that Egr-1 may be a potential novel therapeutic target in human diseases
      complicated by fibrosis. This review summarizes recent advances in understanding
      the regulation and complex functional role of Egr-1 and its related proteins and
      inhibitors in pathological fibrosis.

PMID- 23132751
TI  - Mechanical activation of CaO-based adsorbents for CO(2) capture.
AB  - The reversible cycling of CaO adsorbents to CaCO(3) for high-temperature CO(2)
      capture is substantially improved by mechanical treatment. The mechanical milling
      intensity and conditions of grinding (e.g., wet vs. dry, planetary vs. vibratory
      milling) were determined to be the main factors that control the effectiveness of
      the mechanochemical synthesis to enhance the recycling stability of the sorbents
      prepared. In addition, MgO was used as an example of an inert binder to help
      mitigate CaCO(3) sintering. Wet planetary milling of MgO into CaCO(3) allowed
      efficient particle size reduction and the effective dispersion of MgO throughout
      the particles. Wet planetary milling yielded the most stable sorbents during 50
      cycles of carbonation-calcination.

PMID- 23132752
TI  - Stability of lysosomal membrane in Carcinus maenas acts as a biomarker of
      exposure to pharmaceuticals.
AB  - The presence of pharmaceuticals in the environment is now a major concern given
      their potential adverse effects on organisms, particularly human beings. Because
      the feeding style and habitat of the crab Carcinus maenas make this species
      vulnerable to organic contaminants, it has been used previously in
      ecotoxicological studies. Lysosomal membrane stability (LMS) in crabs is a
      general indicator of cellular well-being and can be visualized by the neutral red
      retention (NRR) assay. LMS in crab hemolymph has been evaluated as a cellular
      biomarker of adverse effects produced by exposure to pharmaceutical compounds.
      Crabs were exposed in the laboratory to four different pharmaceuticals for 28
      days in a semistatic 24-h renewal assay. Filtered seawater was spiked every 2
      days with various concentrations (from 0.1 to 50 MUg . L(-1)) of caffeine,
      ibuprofen, carbamazepine, and novobiocin. Results showed that NRR time, measured
      at day 28, was significantly reduced (p < 0.05) after exposure to environmental
      concentrations of each pharmaceutical (caffeine = 15 MUg . L(-1); carbamazepine =
      1 MUg . L(-1); ibuprofen = 5 MUg . L(-1); and novobiocin = 0.1 MUg . L(-1)) when
      compared with control organisms. The predicted "no environmental effect"
      concentration/measured environmental concentration results showed that the
      selected pharmaceuticals are toxic at environmental concentrations and need
      further assessment. LMS monitoring in crabs is a sensitive tool for evaluating
      exposure to concentrations of selected drugs under laboratory conditions and
      provides a robust tier 1 testing approach (screening biomarker) for rapid
      assessment of marine pollution and environmental impact assessments for analyzing
      pharmaceutical contamination in aquatic environments.

PMID- 23132753
TI  - Isolation and identification of Aeromonas caviae strain KS-1 as TBTC- and lead
      resistant estuarine bacteria.
AB  - Tributyltin chloride (TBTC)- and lead-resistant estuarine bacterium from Mandovi
      estuary, Goa, India was isolated and identified as Aeromonas caviae strain KS-1
      based on biochemical characteristics and FAME analysis. It tolerates TBTC and
      lead up to 1.0 and 1.4 mM, respectively, in the minimal salt medium (MSM)
      supplemented with 0.4 % glucose. Scanning electron microscopy clearly revealed a
      unique morphological pattern in the form of long inter-connected chains of
      bacterial cells on exposure to 1 mM TBTC, whereas cells remained unaltered in
      presence of 1.4 mM Pb(NO3)2 but significant biosorption of lead (8 %) on the cell
      surface of this isolate was clearly revealed by scanning electron microscopy
      coupled with energy dispersive X-ray spectroscopy. SDS-PAGE analysis of whole
      cell proteins of this lead-resistant isolate interestingly demonstrated three
      lead-induced proteins with molecular mass of 15.7, 16.9 and 32.4 kDa,
      respectively, when bacterial cells were grown under the stress of 1.4 mM Pb
      (NO3)2. This clearly demonstrated their possible involvement exclusively in lead
      resistance. A. caviae strain KS-1 also showed tolerance to several other heavy
      metals, viz. zinc, cadmium, copper and mercury. Therefore, we can employ this
      TBTC and lead-resistant bacterial isolate for lead bioremediation and also for
      biomonitoring TBTC from lead and TBTC contaminated environment.

PMID- 23132754
TI  - Levels of heavy metals in tissues of shingi fish (Heteropneustes fossilis) from
      Buriganga River, Bangladesh.
AB  - Heavy metal pollution was reported in commercially valuable freshwater edible
      fish in the Buriganga River, Bangladesh. The concentrations of As, Pb, Cd, Cr,
      Zn, and Cu were investigated in the muscle, gill, stomach, intestine, and liver
      of Heteropneustes fossilis caught at three stations to assess the degree of fish
      pollution by heavy metals. Significant differences in concentrations of analyzed
      elements were observed among different tissues, but not among the stations. The
      ranges of the measured concentrations (MUg/g dry weight) in the tissues of H.
      fossilis were as follows: arsenic concentration was (0.2-0.4), (0.82-0.90), (3.29
      3.99), (2.20-2.80), and (2.41-2.90), that of lead was (1.79-2.20), (4.95-6.55),
      (10.36-13.38), (5.74-9.70), and (18.20-18.79), that of cadmium was (0.3-0.4),
      (2.87-4.27), (1.03-1.63), (1.55-4.59), and (2.25-5.50), that of chromium was
      (1.40-1.70), (3.52-3.72), (2.28-5.29), (2.77-3.79), and (4.25-8.65), that of zinc
      was (24.47-28.82), (16.82-18.80), (20.22-22.20), (22.86-26.68), and (60.82
      67.80), and that of copper was (7.80-8.50), (6.22-6.81), (38.21-44.25), (17.07
      21.03), and (43.24-47.30) in the muscle, gill, stomach, intestine, and liver,
      respectively. This research showed that the liver appeared to be the main heavy
      metal storage tissue, while the muscle had the lowest levels of analyzed metals.
      The concentrations of metal in the muscles not exceeded the acceptable levels for
      a food source for human consumption.

PMID- 23132755
TI  - Receptor model-based source apportionment of particulate pollution in Hyderabad,
      India.
AB  - Air quality in Hyderabad, India, often exceeds the national ambient air quality
      standards, especially for particulate matter (PM), which, in 2010, averaged 82.2
      +/- 24.6, 96.2 +/- 12.1, and 64.3 +/- 21.2 MUg/m(3) of PM10, at commercial,
      industrial, and residential monitoring stations, respectively, exceeding the
      national ambient standard of 60 MUg/m(3). In 2005, following an ordinance passed
      by the Supreme Court of India, a source apportionment study was conducted to
      quantify source contributions to PM pollution in Hyderabad, using the chemical
      mass balance (version 8.2) receptor model for 180 ambient samples collected at
      three stations for PM10 and PM2.5 size fractions for three seasons. The receptor
      modeling results indicated that the PM10 pollution is dominated by the direct
      vehicular exhaust and road dust (more than 60%). PM2.5 with higher propensity to
      enter the human respiratory tracks, has mixed sources of vehicle exhaust,
      industrial coal combustion, garbage burning, and secondary PM. In order to
      improve the air quality in the city, these findings demonstrate the need to
      control emissions from all known sources and particularly focus on the low
      hanging fruits like road dust and waste burning, while the technological and
      institutional advancements in the transport and industrial sectors are bound to
      enhance efficiencies. Andhra Pradesh Pollution Control Board utilized these
      results to prepare an air pollution control action plan for the city.

PMID- 23132756
TI  - UVC-induced mitochondrial degradation via autophagy correlates with mtDNA damage
      removal in primary human fibroblasts.
AB  - Mitochondrial DNA (mtDNA) is more susceptible than nuclear DNA to helix
      distorting damage via exposure to environmental genotoxins, partially due to a
      lack of nucleotide excision repair. Thus, this damage is irreparable and
      persistent in mtDNA in the short term. We recently found that helix-distorting
      mtDNA damage induced by ultraviolet C radiation (UVC) is gradually removed in
      Caenorhabditis elegans and that removal is dependent upon autophagy and
      mitochondrial dynamics. We here report the effects of UVC exposure on mitophagy,
      mitochondrial morphology, and indicators of mitochondrial function in mammalian
      cells. Exposure to UVC induced autophagy within 24 h; nonetheless, significant
      mitochondrial degradation was not observed until 72 h post exposure.
      Mitochondrial mass, morphology, and function were not significantly altered.
      These data further support the idea that persistent mtDNA damage is removed by
      autophagy and also suggest a powerful compensatory capacity for dealing with
      mtDNA damage.

PMID- 23132757
TI  - Enhanced cardiac protein glycosylation (O-GlcNAc) of selected mitochondrial
      proteins in rats artificially selected for low running capacity.
AB  - O-linked beta-N-acetyl glucosamine (O-GlcNAc) is a posttranslational modification
      consisting of a single N-acetylglucosamine moiety attached by an O-beta
      glycosidic linkage to serine and threonine residues of both nuclear and cytosolic
      proteins. Analogous to phosphorylation, the modification is reversible and
      dynamic, changing in response to stress, nutrients, hormones, and exercise. Aims
      of this study were to examine differences in O-GlcNAc protein modification in the
      cardiac tissue of rats artificially selected for low (LCR) or high (HCR) running
      capacity. Hyperinsulinemic-euglycemic clamps in conscious animals assessed
      insulin sensitivity while 2-[(14)C] deoxyglucose tracked both whole body and
      tissue-specific glucose disposal. Immunoblots of cardiac muscle examined global O
      GlcNAc modification, enzymes that control its regulation (OGT, OGA), and specific
      proteins involved in mitochondrial oxidative phosphorylation. LCR rats were
      insulin resistant disposing of 65% less glucose than HCR. Global tissue O-GlcNAc,
      OGT, OGA, and citrate synthase were similar between groups. Analysis of cardiac
      proteins revealed enhanced O-GlcNAcylation of mitochondrial Complex I, Complex
      IV, VDAC, and SERCA in LCR compared with HCR. These results are the first to
      establish an increase in specific protein O-GlcNAcylation in LCR animals that may
      contribute to progressive mitochondrial dysfunction and the pathogenesis of
      insulin resistance observed in the LCR phenotype.

PMID- 23132759
TI  - Early genetic responses in rat vascular tissue after simulated diving.
AB  - Diving causes a transient reduction of vascular function, but the mechanisms
      behind this are largely unknown. The aim of this study was therefore to analyze
      genetic reactions that may be involved in acute changes of vascular function in
      divers. Rats were exposed to 709 kPa of hyperbaric air (149 kPa Po(2)) for 50 min
      followed by postdive monitoring of vascular bubble formation and full genome
      microarray analysis of the aorta from diving rats (n = 8) and unexposed controls
      (n = 9). Upregulation of 23 genes was observed 1 h after simulated diving. The
      differential gene expression was characteristic of cellular responses to
      oxidative stress, with functions of upregulated genes including activation and
      fine-tuning of stress-responsive transcription, cytokine/cytokine receptor
      signaling, molecular chaperoning, and coagulation. By qRT-PCR, we verified
      increased transcription of neuron-derived orphan receptor-1 (Nr4a3), plasminogen
      activator inhibitor 1 (Serpine1), cytokine TWEAK receptor FN14 (Tnfrsf12a),
      transcription factor class E basic helix-loop-helix protein 40 (Bhlhe40), and
      adrenomedullin (Adm). Hypoxia-inducible transcription factor HIF1 subunit HIF1
      alpha was stabilized in the aorta 1 h after diving, and after 4 h there was a
      fivefold increase in total protein levels of the procoagulant plasminogen
      activator inhibitor 1 (PAI1) in blood plasma from diving rats. The study did not
      have sufficient power for individual assessment of effects of hyperoxia and
      decompression-induced bubbles on postdive gene expression. However, differential
      gene expression in rats without venous bubbles was similar to that of all the
      diving rats, indicating that elevated Po(2) instigated the observed genetic
      reactions.

PMID- 23132758
TI  - Current analysis platforms and methods for detecting copy number variation.
AB  - Copy number variation (CNV), generated through duplication or deletion events
      that affect one or more loci, is widespread in the human genomes and is often
      associated with functional consequences that may include changes in gene
      expression levels or fusion of genes. Genome-wide association studies indicate
      that some disease phenotypes and physiological pathways might be impacted by CNV
      in a small number of characterized genomic regions. However, the pervasiveness
      and full impact of such variation remains unclear. Suitable analytic methods are
      needed to thoroughly mine human genomes for genomic structural variation, and to
      explore the interplay between observed CNV and disease phenotypes, but many
      medical researchers are unfamiliar with the features and nuances of recently
      developed technologies for detecting CNV. In this article, we evaluate a suite of
      commonly used and recently developed approaches to uncovering genome-wide CNVs
      and discuss the relative merits of each.

PMID- 23132760
TI  - Transcriptome of the NTS in exercise-trained spontaneously hypertensive rats:
      implications for NTS function and plasticity in regulating blood pressure.
AB  - The nucleus tractus solitarii (NTS) controls the cardiovascular system during
      exercise, and alteration of its function may underlie exercise-induced
      cardiovascular adaptation. To understand the molecular basis of the NTS's
      plasticity in regulating blood pressure (BP) and its potential contribution to
      the antihypertensive effects, we characterized the gene expression profiles at
      the level of the NTS after long-term daily wheel running in spontaneously
      hypertensive rats (SHRs). Genome-wide microarray analysis was performed to screen
      for differentially expressed genes in the NTS between exercise-trained (12 wk)
      and control SHRs. Pathway analysis using the Kyoto Encyclopedia of Genes and
      Genomes database revealed that daily exercise altered the expression levels of
      NTS genes that are functionally associated with metabolic pathways (5 genes),
      neuroactive ligand-receptor interactions (4 genes), cell adhesion molecules (3
      genes), and cytokine-cytokine receptor interactions (3 genes). One of the genes
      that belonged to the neuroactive ligand-receptor interactions category was
      histamine receptor H(1). Since we confirmed that the pressor response induced by
      activation of this receptor is increased after long-term daily exercise, it is
      suggested that functional plasticity in the histaminergic system may mediate the
      facilitation of blood pressure control in response to exercise but may not be
      involved in the lowered basal BP level found in exercise-trained SHRs. Since
      abnormal inflammatory states in the NTS are known to be prohypertensive in SHRs,
      altered gene expression of the inflammatory molecules identified in this study
      may be related to the antihypertensive effects in exercise-trained SHRs, although
      such speculation awaits functional validation.

PMID- 23132761
TI  - On prebiotic ecology, supramolecular selection and autopoiesis.

PMID- 23132763
TI  - Solid-phase synthesis of structurally diverse heterocycles by an amide-ketone
      condensation/N-acyliminium pictet-spengler sequence.
AB  - An efficient approach for the solid-phase synthesis of structurally diverse
      heterocyclic compounds is presented. Under acidic reaction conditions, peptidic
      levulinamides undergo intramolecular ketone-amide condensation reactions to form
      cyclic N-acyliminium intermediates. In the presence of a tethered nucleophile, a
      second cyclization reaction results in the formation of a fused bicyclic ring
      system. The scope of the methodology was demonstrated by several combinations of
      substituted ketones and nucleophiles, the latter conveniently originating from
      amino acids with functionalized side chains, such as tryptophan, substituted
      phenylalanines, and cysteine. The cyclization sequence provides
      diastereomerically pure products in high yields. In one extension of the
      methodology, the resulting relative stereochemistry of the products enables the
      formation of bridged ring systems by a unique cyclative release mechanism.

PMID- 23132762
TI  - Open questions on the origin of life at anoxic geothermal fields.
AB  - We have recently reconstructed the 'hatcheries' of the first cells by combining
      geochemical analysis with phylogenomic scrutiny of the inorganic ion requirements
      of universal components of modern cells (Mulkidjanian et al. Proc Natl Acad Sci U
      S A 109:E821-830, 2012). These ubiquitous, and by inference primordial, proteins
      and functional systems show affinity to and functional requirement for K+, Zn2+,
      Mn2+, and phosphate. Thus, protocells must have evolved in habitats with a high
      K+/Na+ ratio and relatively high concentrations of Zn, Mn and phosphorous
      compounds. Geochemical reconstruction shows that the ionic composition conducive
      to the origin of cells could not have existed in marine settings but is
      compatible with emissions of vapor-dominated zones of inland geothermal systems.
      Under an anoxic, CO2-dominated atmosphere, the ionic composition of pools of
      cool, condensed vapor at anoxic geothermal fields would resemble the internal
      milieu of modern cells. Such pools would be lined with porous silicate minerals
      mixed with metal sulfides and enriched in K+ ions and phosphorous compounds. Here
      we address some questions that have appeared in print after the publication of
      our anoxic geothermal field scenario. We argue that anoxic geothermal fields,
      which were identified as likely cradles of life by using a top-down approach and
      phylogenomics analysis, could provide geochemical conditions similar to those
      which were suggested as most conducive for the emergence of life by the chemists
      who pursuit the complementary bottom-up strategy.

PMID- 23132764
TI  - Frequency shift in graphene-enhanced Raman signal of molecules.
AB  - Graphene-enhanced Raman scattering (GERS) is emerging as an important method due
      to the need for highly reproducible, quantifiable, and biocompatible active
      substrates. As a result of its unique two-dimensional carbon structure, graphene
      provides particularly large enhanced Raman signals for molecules adsorbed on its
      surface. In this work, the GERS signals of a test molecule, 4-mercaptobenzoic
      acid (4-MBA), with reproducible enhancement factors are discussed and compared
      with surface-enhanced Raman scattering (SERS) signals from highly active
      substrates, covered with spherical silver nanoparticles. It is shown that
      chemical interactions between the molecule and graphene can result in a frequency
      shift in the graphene-enhanced Raman signal of the molecule.

PMID- 23132765
TI  - Body image in recently diagnosed young women with early breast cancer.
AB  - OBJECTIVE: To assess body image concerns among young women following a breast
      cancer diagnosis. METHODS: A total of 419 women with recently diagnosed stage 0
      III breast cancer were surveyed following enrollment as part of a prospective
      cohort study of women age 40 or younger at diagnosis. Body image was assessed
      using three items from the psycho-social scale of the Cancer Rehabilitation
      Evaluation System (CARES). CARES scores range from 0 to 4, with higher scores
      indicative of greater image concerns. Mean CARES scores were calculated and
      compared between treatment groups using t-tests and analysis of variance.
      Multiple linear regression models were fit to evaluate the relationship between
      physical and psychological factors and body image. RESULTS: Mean time from
      diagnosis to completion of the baseline survey was 5.2 months. The mean CARES
      score for all women was 1.28. Mean CARES scores in the mastectomy-only group
      (1.87) and in the mastectomy with reconstruction group (1.52) were significantly
      higher (p < 0.0001) compared with the scores in the lumpectomy group (0.85),
      indicating that radical surgery was associated with more body image concerns.
      Radiation (p = 0.01), anxiety (p = 0.0001), depression (p < 0.0001), fatigue (p =
      0.04), musculoskeletal pain symptoms (p < 0.0001), weight gain (p = 0.01), and
      weight loss (p = 0.02), in addition to surgery type (p < 0.0001), were all
      associated with more body image concerns in the multi-variable analysis.
      CONCLUSION: This analysis highlights the impact of treatment, along with physical
      and psychological factors, on body image early in the survivorship period. Our
      findings provide targets for potential future intervention and may aid young
      women in the surgical decision-making process.

PMID- 23132766
TI  - Cancer-associated somatic DICER1 hotspot mutations cause defective miRNA
      processing and reverse-strand expression bias to predominantly mature 3p strands
      through loss of 5p strand cleavage.
AB  - Our group recently described recurrent somatic mutations of the miRNA processing
      gene DICER1 in non-epithelial ovarian cancer. Mutations appeared to be clustered
      around each of four critical metal-binding residues in the RNase IIIB domain of
      DICER1. This domain is responsible for cleavage of the 3' end of the 5p miRNA
      strand of a pre-mRNA hairpin. To investigate the effects of these cancer
      associated 'hotspot' mutations, we engineered mouse DICER1-deficient ES cells to
      express wild-type and an allelic series of the mutant DICER1 variants. Global
      miRNA and mRNA profiles from cells carrying the metal-binding site mutations were
      compared to each other and to wild-type DICER1. The miRNA and mRNA profiles
      generated through the expression of the hotspot mutations were virtually
      identical, and the DICER1 hotspot mutation-carrying cells were distinct from both
      wild-type and DICER1-deficient cells. Further, miRNA profiles showed that mutant
      DICER1 results in a dramatic loss in processing of mature 5p miRNA strands but
      were still able to create 3p strand miRNAs. Messenger RNA (mRNA) profile changes
      were consistent with the loss of 5p strand miRNAs and showed enriched expression
      for predicted targets of the lost 5p-derived miRNAs. We therefore conclude that
      cancer-associated somatic hotspot mutations of DICER1, affecting any one of four
      metal-binding residues in the RNase IIIB domain, are functionally equivalent with
      respect to miRNA processing and are hypomorphic alleles, yielding a global loss
      in processing of mature 5p strand miRNA. We further propose that this resulting
      3p strand bias in mature miRNA expression likely underpins the oncogenic
      potential of these hotspot mutations.

PMID- 23132767
TI  - CO(2) -responsive "smart" single-walled carbon nanotubes.
AB  - A new type of "smart" single-walled carbon nanotubes is created by wrapping a
      pyrene-labeled CO(2) -responsive polymer via pi-pi stacking. The polymer/SWNT
      hybrids not only undergo a hydrophobic-hydrophilic transition upon CO(2) 
      stimulus of CO(2)  in a mixed solvent, but also exhibit switchable
      dispersion/aggregation states upon the alternate bubbling of CO(2)  and N(2)  in
      pure water.

PMID- 23132768
TI  - Controlled synthesis of monodisperse SiO(2)--TiO(2) microspheres with a yolk
      shell structure as effective photocatalysts.
AB  - Monodisperse yolk-shell SiO(2) -TiO(2) microspheres were synthesized using core
      shell silica microspheres as templates. In the absence of prior surface
      modifications, a uniform coating of the TiO(2) layer on the core-shell silica was
      achieved through a sol-gel route. Mesoporous silica shells between the outer
      TiO(2) shell and the SiO(2) core were selectively removed by using a weak base,
      yielding yolk-shell SiO(2) -TiO(2) microspheres (ys-SiO(2) @TiO(2) ). Using the
      same templates, we synthesized Pt-encased microspheres (SiO(2) @Pt-TiO(2) ), in
      which Pt nanoparticles are embedded between the SiO(2) core and the TiO(2) shell.
      Selective etching of the silica shells in SiO(2) @Pt-TiO(2) yields Pt-encased
      yolk-shell SiO(2) -TiO(2) microspheres (ys-SiO(2) @< Pt >TiO(2) ), which contain
      void spaces suitable for use as nanoreactors. The ys-SiO(2) @< Pt >TiO(2)
      catalyst shows enhanced hydrogen production from water under UV-light irradiation
      presumably as a result of multiple reflections within the void spaces and can be
      reused without losing their activity. Moreover, this core-shell template method
      is effective for the synthesis of other yolk-shell microspheres with different
      metal oxides.

PMID- 23132769
TI  - Impact of lesion length on functional significance in intermediate coronary
      lesions.
AB  - BACKGROUND: Myocardial fractional flow reserve (FFR) is useful in the evaluation
      of coronary lesion ischemia. However, the impact of lesion length on FFR has not
      been adequately assessed. HYPOTHESIS: We hypothesized that lesion length would
      influence functional significance in intermediate coronary lesions. METHODS: FFR
      measurements were assessed in 136 patients (163 lesions) with stable angina who
      had >40% stenotic coronary lesion by quantitative coronary angiography (QCA). One
      hundred sixty-three lesions were classified as intermediate (40%-70% stenosis;
      n=107; group I) or significant (>=70%; n=56; group S) by QCA. We assessed the
      relationships between lesion length, coronary stenosis, and FFR in these 163
      lesions. RESULTS: Regression analysis revealed an inverse correlation between the
      percentage of diameter stenosis (%DS) and FFR in group S (r = -0.83, P < 0.0001).
      In group I, no significant correlation was found between %DS and FFR (r = -0.06,
      P = 0.55), whereas lesion length was significantly inversely correlated with FFR
      (r = -0.79, P < 0.0001). Receiver operating characteristic curve analysis
      demonstrated that the best cutoff value for predicting an FFR value <0.80 was a
      lesion length >16.1 mm in group I (sensitivity, 86%; specificity, 94%).
      CONCLUSIONS: These study findings suggest that lesion length has a
      physiologically significant impact on intermediate-grade coronary lesions.

PMID- 23132770
TI  - Modulation of acid phosphatase and lactic dehydrogenase in hexachlorocyclohexane
      induced hepatocarcinogenesis in mice.
AB  - The present study was designed to elucidate the involvement of acid phosphatase
      (ACP) in metastasis and lactate dehydrogenase (LDH) as an immediate compensatory
      alleviation mechanism for energy stress in liver lesions induced by
      hexachlorocyclohexane in Swiss mice. Animals were continuously exposed to
      hexachlorocyclohexane (500 ppm) for 2, 4, and 6 months. Neoplastic nodules and
      tumors developed after continuous exposure for 4 and 6 months, respectively. The
      distribution pattern of both enzymes markedly varied in neoplastic nodules and
      tumors. Intense ACP activity was more observed only in sinusoids and blood
      vessels of neoplastic nodule, whereas an overall increase in ACP activity was
      observed in the tumor. Noticeably, a significant decline in LDH activity was
      noted after 2 and 4 months of exposure, whereas LDH in a tumor region showed
      intense enzymatic activity. The role of acid phosphate in metastasis and LDH in
      oxidative stress during hepatocarcinogenesis induced by hexachlorocyclohexane has
      been discussed.

PMID- 23132771
TI  - Catalytic asymmetric direct vinylogous Michael addition of deconjugated
      butenolides to maleimides for the construction of quaternary stereogenic centers.

PMID- 23132772
TI  - Self-assembled polymeric chelate nanoparticles as potential theranostic agents.
AB  - Improvements in cancer diagnostics and therapy have recently attracted the
      interest of many different branches of science. This study presents one of the
      new possible approaches in the diagnostics and therapy of cancer by using
      polymeric chelates as carriers. Graft copolymers with a backbone containing 8
      hydroxyquinoline-5-sulfonic acid chelating groups and poly(ethylene oxide)
      hydrophilic grafts are synthesized and characterized. The polymers assemble and
      form particles after the addition of a biometal cation, such as iron or copper.
      The obtained nanoparticles exhibit a hydrodynamic diameter of around 25 nm and a
      stability of at least several hours, which are counted as essential parameters
      for biomedical purposes. To prove their biodegradability, a model degradation
      with deferoxamine is performed and, together with high radiolabeling efficiency
      with copper-64, their possible use for nuclear medicine purposes is demonstrated.

PMID- 23132773
TI  - An ion-induced low-oil-adhesion organic/inorganic hybrid film for stable
      superoleophobicity in seawater.
AB  - Superoleophobicity under seawater: An ion-induced low-oil-adhesion film with
      underwater superoleophobicity is prepared by a typical layer-by-layer (LBL)
      method. Under an artificial marine environment with high ion-strength, the
      prepared polyelectrolytes/AuNPs hybrid film becomes rougher and possesses a
      higher water ratio, which in turn endows the film with superoleophobicity and low
      underwater oil adhesion. The as-prepared film shows excellent environmental
      stability in artificial seawater. This study provides a new strategy for
      controlling the self-cleaning property and accelerating the development of stable
      underwater superoleophobic films.

PMID- 23132774
TI  - High-specificity single-tube multiplex genotyping using Ribo-PAP PCR, tag
      primers, alkali cleavage of RNA/DNA chimeras and MALDI-TOF MS.
AB  - Here, we describe a high-throughput, single-tube, allele-specific ribonucleotide
      analog pyrophosphorolysis-activated polymerization (ribo-PAP) PCR multiplex
      genotyping and resequencing method. An RNA/DNA chimeric PCR product is generated
      using genomic DNA as starting template, a panel of allele-selective 5'-tagged
      primers, a reverse primer, one nucleotide in the ribo-form (90-100%), the other
      nucleotides in the deoxy-form, a DNA polymerase capable of incorporating
      ribonucleotides, a suitable buffer and thermal cycling. The RNA/DNA chimeric PCR
      products are fragmented by treatment with alkali and analyzed by mass
      spectrometry. All allele-selective primers have a 5' repetitive motif where each
      repeat unit has a unique, distinct mass upon reverse copying and alkali
      fragmentation. The mass of the complement repeat fragment or flag identifies the
      primer or primers that were recruited in the ribo-PAP PCR. The method readily
      identifies homozygous and heterozygous positions in simplex or duplex ribo-PAP
      PCR. Many different tags can be analyzed simultaneously. The assay can genotype
      several SNPs in a single tube. It thus constitutes the simplest genotyping
      protocol with multiplex analysis. This novel genotyping and resequencing protocol
      was applied to different genomic loci: NOS1 and H19 in 30 individuals in simplex
      ribo-PAP PCR and at two SLCO1B1 loci in 95 individuals in duplex ribo-PAP PCR.

PMID- 23132775
TI  - Granular bamboo-derived activated carbon for high CO(2) adsorption: the dominant
      role of narrow micropores.
AB  - Cost-effective biomass-derived activated carbons with a high CO(2) adsorption
      capacity are attractive for carbon capture. Bamboo was found to be a suitable
      precursor for activated carbon preparation through KOH activation. The bamboo
      size in the range of 10-200 mesh had little effect on CO(2) adsorption, whereas
      the KOH/C mass ratio and activation temperature had a significant impact on CO(2)
      adsorption. The bamboo-derived activated carbon had a high adsorption capacity
      and excellent selectivity for CO(2) , and also the adsorption process was highly
      reversible. The adsorbed amount of CO(2) on the granular activated carbon was up
      to 7.0 mmol g(-1) at 273 K and 1 bar, which was higher than almost all carbon
      materials. The pore characteristics of activated carbons responsible for high
      CO(2) adsorption were fully investigated. Based on the analysis of narrow
      micropore size distribution of several activated carbons prepared under different
      conditions, a more accurate micropore range contributing to CO(2) adsorption was
      proposed. The volume of micropores in the range of 0.33-0.82 nm had a good linear
      relationship with CO(2) adsorption at 273 K and 1 bar, and the narrow micropores
      of about 0.55 nm produced the major contribution, which could be used to evaluate
      CO(2) adsorption on activated carbons.

PMID- 23132776
TI  - Differential effect of DDT, DDE, and DDD on COX-2 expression in the human
      trophoblast derived HTR-8/SVneo cells.
AB  - The purpose of this study was to investigate the effect of 1,1,1-trichloro-2,2
      bis-(chlorophenyl)ethane (DDT), 1,1-bis-(chlorophenyl)-2,2-dichloroethene (DDE),
      and 1,1-dichloro-2,2-bis(chlorophenyl)ethane (DDD) isomers on COX-2 expression in
      a human trophoblast-derived cell line. Cultured HTR-8/SVneo trophoblast cells
      were exposed to DDT isomers and its metabolites for 24 h, and COX-2 mRNA and
      protein expression were assessed by RT-PCR, Western blotting, and ELISA.
      Prostaglandin E2 production was also measured by ELISA. Both COX-2 mRNA and
      protein were detected under control (unexposed) conditions in the HTR-8/SVneo
      cell line. COX-2 protein expression and prostaglandin E2 production but not COX-2
      mRNA levels increased only after DDE and DDD isomers exposure. It is concluded
      that DDE and DDD exposure induce the expression of COX-2 protein, leading to
      increased prostaglandin E2 production. Interestingly, the regulation of COX-2 by
      these organochlorines pesticides appears to be at the translational level.

PMID- 23132777
TI  - Curcumin serves as a human kv1.3 blocker to inhibit effector memory T lymphocyte
      activities.
AB  - Curcumin, the principal active component of turmeric, has long been used to treat
      various diseases in India and China. Recent studies show that curcumin can serve
      as a therapeutic agent for autoimmune diseases via a variety of mechanisms.
      Effector memory T cells (T(EM), CCR7- CD45RO+ T lymphocyte) have been
      demonstrated to play a crucial role in the pathogenesis of T cell-mediated
      autoimmune diseases, such as multiple sclerosis (MS) or rheumatoid arthritis
      (RA). Kv1.3 channels are predominantly expressed in T(EM) cells and control T(EM)
      activities. In the present study, we examined the effect of curcumin on human
      Kv1.3 (hKv1.3) channels stably expressed in HEK-293 cells and its ability to
      inhibit proliferation and cytokine secretion of T(EM) cells isolated from
      patients with MS or RA. Curcumin exhibited a direct blockage of hKv1.3 channels
      in a time-dependent and concentration-dependent manner. Moreover, the activation
      curve was shifted to a more positive potential, which was consistent with an open
      channel blockade. Paralleling hKv1.3 inhibition, curcumin significantly inhibited
      proliferation and interferon-gamma secretion of T(EM) cells. Our findings
      demonstrate that curcumin is able to inhibit proliferation and proinflammatory
      cytokine secretion of T(EM) cells probably through inhibition of hKv1.3 channels,
      which contributes to the potency of curcumin for the treatment of autoimmune
      diseases. This is probably one of pharmacological mechanisms of curcumin used to
      treat autoimmune diseases.

PMID- 23132778
TI  - Unique photothermal response and sustained photothermal effect of pH-responsive
      gold-nanoparticle aggregates.
AB  - Hot gold: The photothermal response upon pulsed laser irradiation is studied for
      pH-responsive gold-nanoparticle aggregates and compared to that of gold nanorods.
      The aggregates show a slight red shift in the absorption spectrum and retain the
      photothermal effect, whereas the nanorods lose the photothermal effect and
      exhibit a stark blue shift in the absorption.

PMID- 23132779
TI  - Clinical applications of the computed tomography angiography spot sign in acute
      intracerebral hemorrhage: a review.

PMID- 23132780
TI  - High blood pressure, physical and cognitive function, and risk of stroke in the
      oldest old: the Leiden 85-plus Study.
AB  - BACKGROUND AND PURPOSE: Epidemiological studies have shown mixed findings on the
      association between hypertension and stroke in the oldest old. Heterogeneity of
      the populations under study may underlie variation in outcomes. We examined
      whether the level of physical and cognitive function moderates the association
      between blood pressure and stroke. METHODS: We included 513 subjects aged 85
      years old from the population-based Leiden 85-plus Study. Systolic blood
      pressure, diastolic blood pressure, mean arterial pressure, and pulse pressure
      were measured at baseline. Activities of daily living and Mini-Mental State
      Examination were assessed to estimate level of physical and cognitive function,
      respectively. Five-year risk of stroke was estimated with Cox regression
      analysis. RESULTS: In the entire cohort, there were no associations between
      various measures of blood pressure and risk of stroke except for the inverse
      relation between pulse pressure and stroke risk (hazard ratio [HR], 0.80 [95%
      confidence interval [CI], 0.66-0.98]). Among subjects with impaired physical
      functioning, higher systolic blood pressure (HR, 0.74 [95% CI, 0.59-0.92]), mean
      arterial pressure (HR: 0.68 [95% CI, 0.47-0.97]), and pulse pressure (HR, 0.71
      [95% CI, 0.55-0.93]) were associated with reduced risk of stroke. Likewise, among
      subjects with impaired cognitive functioning, higher systolic blood pressure was
      associated with reduced risk of stroke (HR, 0.80 [95% CI, 0.65-0.98]). In
      subjects with unimpaired cognitive functioning, higher diastolic blood pressure
      (HR: 1.98 [95% CI, 1.21-3.22]) and mean arterial pressure (HR, 1.70 [95% CI, 1.08
      2.68]) were associated with higher risk of stroke. CONCLUSIONS: Our findings
      suggest that impaired physical and cognitive function moderates the association
      between blood pressure and stroke.

PMID- 23132781
TI  - Racial and ethnic disparities in the treatment of unruptured intracranial
      aneurysms: a study of the Nationwide Inpatient Sample 2001-2009.
AB  - BACKGROUND AND PURPOSE: Minorities in the United States have less access to
      healthcare system resources, especially preventative treatments. We sought to
      determine whether racial and sex disparities existed in the treatment of
      unruptured intracranial aneurysms. METHODS: Using the Nationwide Inpatient
      Sample, hospitalizations for clipping and coiling of intracranial aneurysms from
      2001 to 2009 were identified by cross-matching International Classification of
      Diseases, 9th Revision codes for diagnosis of unruptured aneurysm and
      subarachnoid hemorrhage (SAH) with procedure codes for clipping or coiling of
      cerebral aneurysms. Demographic information analyzed included age (<50, 50-64, 65
      79, and >=80 years), race (white, black, Hispanic, Asian/Pacific Islander), sex,
      income quartile, primary payer (Medicare, Medicaid, private insurance, self-pay,
      no charge, other), and Charlson comorbidity index. RESULTS: When compared with
      patients treated for SAH, those treated for unruptured intracranial aneurysm were
      significantly more likely to be women (75.0% versus 69.0%; P<0.0001). In all,
      9.7% of patients receiving treatment for SAH were self-payers versus 3.0% of
      patients being treated for unruptured intracranial aneurysm (P<0.0001). In all,
      62.2% of patients receiving treatment for SAH were white compared with 76.4% of
      patients being treated for unruptured intracranial aneurysm (P<0.0001). There was
      a higher proportion of black, Hispanic, and Asian patients in the SAH treatment
      group when compared with the unruptured aneurysm treatment group (P<0.0001 for
      all groups). CONCLUSIONS: When compared with patients undergoing treatment for
      SAH, patients undergoing surgical and endovascular treatment for unruptured
      intracranial aneurysm are generally from higher socioeconomic strata and are more
      likely to be insured, women, and white. Future studies are needed to determine
      the underlying causes and solutions for this disparity.

PMID- 23132782
TI  - Timing of stroke in patients undergoing total hip replacement and matched
      controls: a nationwide cohort study.
AB  - BACKGROUND AND PURPOSE: Stroke is a potentially fatal complication of total hip
      replacements (THR). However, timing of stroke in THR patients compared with
      matched controls and influence of drug use remain unknown. The objective of this
      study was to determine timing of stroke in patients with THR compared with
      matched control subjects. METHODS: A nationwide cohort study was conducted within
      the Danish registers (1998-2007). Included patients were those with a primary THR
      in the study period (n=66,583) and were matched by age, sex, and region to three
      referent subjects without THR or total knee replacements. Time-dependent Cox
      models were used to derive hazard ratios and were adjusted for disease history
      and drug use. RESULTS: A 4.7-fold increased risk of ischemic stroke (adjusted
      hazard ratio, 4.69; 95% CI, 3.12-7.06), and a 4.4-fold increased risk of
      hemorrhagic stroke (adjusted hazard ratio, 4.40; 95% CI, 2.01-9.62) were found
      within 2 weeks following THR, compared with matched controls. The risk remained
      elevated during the first 6 postoperative weeks for ischemic stroke, and the
      first 12 weeks for hemorrhagic stroke. Outpatient antiplatelet drug use lowered
      the 6-week hazard ratios for ischemic stroke by 70%, although not affecting risk
      of hemorrhagic stroke. CONCLUSIONS: This study shows, that THR patients have a
      4.7-fold increased risk of ischemic stroke, and a 4.4-fold increased risk of
      hemorrhagic stroke during the first 2 weeks postsurgery. Risk assessment of
      stroke in individual patients undergoing THR (ie, evaluate other risk factors for
      stroke) should be considered during the first 6 to 12 weeks.

PMID- 23132783
TI  - MRI biomarkers in acute ischemic stroke: a conceptual framework and historical
      analysis.

PMID- 23132784
TI  - Mesoporous siliconiobium phosphate as a pure Bronsted acid catalyst with
      excellent performance for the dehydration of glycerol to acrolein.
AB  - The development of solid acid catalysts that contain a high density of Bronsted
      acid sites with suitable acidity, as well as a long lifetime, is one of great
      challenges for the efficient dehydration of glycerol to acrolein. Herein, we
      report on a mesoporous siliconiobium phosphate (NbPSi-0.5) composite, which is a
      promising solid Bronsted acid that is a potential candidate for such a high
      performance catalyst. A variety of characterization results confirm that NbPSi
      0.5 contains nearly pure Bronsted acid sites and has well-defined large
      mesopores. In addition, NbPSi-0.5 contains a similar amount of acid sites and
      exhibits weaker acidity than that of the highly acidic niobium phosphate and HZSM
      5 zeolite. NbPSi-0.5 is quite stable and has a high activity for the dehydration
      of glycerol. The stability of NbPSi-0.5 is about three times higher than that of
      the reported catalyst. The significantly enhanced catalytic performance of NbPSi
      0.5 can be attributed to 1) nearly pure Bronsted acidity, which suppresses side
      reactions that lead to coke formation; 2) a significant reduction of pore
      blocking due to the mesopores; and 3) a decrease in the amount and oxidation
      temperature of coke.

PMID- 23132785
TI  - MRT letter: application of novel "in vivo cryotechnique" in living animal
      kidneys.
AB  - AIM: To compare the influence of different fixation procedures on morphologic
      studies in living mice, and to identify the advantages of the "in vivo
      cryotechnique" (IVCT). METHODS: We prepared mouse kidneys using four different
      fixation methods: conventional immersion-fixation, quick-freezing following
      resection of the kidney, quick-freezing following perfusion-fixation, and IVCT.
      RESULTS: Kidney glomeruli were noticeably contracted after conventional immersion
      fixation or quick-freezing following resection compared to glomeruli from tissues
      preserved by the IVCT. With the IVCT, both albumin and IgG were colocalized
      exclusively along or within the glomerular capillary loops; however,
      immunoreactivity of these proteins in the other three methods was clearly
      detected in the Bowman's space and apical cytoplasm of the proximal tubules. With
      the IVCT, immunoreactivity of collagen type IV was very weak at the glomerular
      basement membrane (GBM) until microwave treatment, which increased its
      immunoreactivity. In contrast, the immunoreactivity was clearly detected at the
      GBM with or without microwave treatment with quick-freezing following perfusion
      fixation. With quick-freezing following perfusion-fixation, aquaporin-1 (AQP-1)
      was irregularly distributed in a disorganized manner on the brush border and
      apical cell membrane along the proximal tubules. But AQP-1 was labeled intensely
      and regularly along the brush border and apical cell membrane andonly weakly
      along the basolateral membrane of the proximal tubules with the IVCT. CONCLUSION:
      The IVCT may reliably maintain soluble serum proteins and renal intrinsic
      proteins such as AQP-1 in situ and capture transient structures and functional
      changes in vivo.

PMID- 23132786
TI  - Characteristics and significance of intergenic polyadenylated RNA transcription
      in Arabidopsis.
AB  - The Arabidopsis (Arabidopsis thaliana) genome is the most well-annotated plant
      genome. However, transcriptome sequencing in Arabidopsis continues to suggest the
      presence of polyadenylated (polyA) transcripts originating from presumed
      intergenic regions. It is not clear whether these transcripts represent novel
      noncoding or protein-coding genes. To understand the nature of intergenic polyA
      transcription, we first assessed its abundance using multiple messenger RNA
      sequencing data sets. We found 6,545 intergenic transcribed fragments (ITFs)
      occupying 3.6% of Arabidopsis intergenic space. In contrast to transcribed
      fragments that map to protein-coding and RNA genes, most ITFs are significantly
      shorter, are expressed at significantly lower levels, and tend to be more data
      set specific. A surprisingly large number of ITFs (32.1%) may be protein coding
      based on evidence of translation. However, our results indicate that these
      "translated" ITFs tend to be close to and are likely associated with known genes.
      To investigate if ITFs are under selection and are functional, we assessed ITF
      conservation through cross-species as well as within-species comparisons. Our
      analysis reveals that 237 ITFs, including 49 with translation evidence, are under
      strong selective constraint and relatively distant from annotated features. These
      ITFs are likely parts of novel genes. However, the selective pressure imposed on
      most ITFs is similar to that of randomly selected, untranscribed intergenic
      sequences. Our findings indicate that despite the prevalence of ITFs, apart from
      the possibility of genomic contamination, many may be background or noisy
      transcripts derived from "junk" DNA, whose production may be inherent to the
      process of transcription and which, on rare occasions, may act as catalysts for
      the creation of novel genes.

PMID- 23132788
TI  - Modulatory effects of curcumin and green tea extract against experimentally
      induced pulmonary fibrosis: a comparison with N-acetyl cysteine.
AB  - The study was aimed to investigate the protective effect of green tea extract
      (GTE), curcumin, and N-acetyl cysteine (NAC) on experimentally induced pulmonary
      fibrosis. Curcumin (200 mg/kg b.w), GTE (150 mg/kg b.w), and NAC (490 mg/kg b.w)
      were administered orally for 14 days with concomitant administration of
      cyclophosphamide (CP). Lung fibrosis was assessed by measuring hydroxyproline and
      elastin levels and confirmed by histopathological examination. Oxidative stress
      was also observed in the CP group. Lung myeloperoxidase activity was
      significantly decreased in animals of the CP group. N-acetyl-beta-d
      glucosaminidase, leukotriene C4, and protein were increased in bronchoalveolar
      lavage fluid (BALF). Transforming growth factor-beta, interleukin -1beta, and
      histamine were increased in both serum and BALF. All modulators markedly
      attenuated the altered biochemical parameters as compared to CP-treated rats.
      These results suggest the possibility of using these treatments as protective
      agents with chemotherapy and as protective agents for lung fibrosis.

PMID- 23132787
TI  - RRP41L, a putative core subunit of the exosome, plays an important role in seed
      germination and early seedling growth in Arabidopsis.
AB  - In prokaryotic and eukaryotic cells, the 3'-5'-exonucleolytic decay and
      processing of RNAs are essential for RNA metabolism. However, the understanding
      of the mechanism of 3'-5'-exonucleolytic decay in plants is very limited. Here,
      we report the characterization of an Arabidopsis (Arabidopsis thaliana) transfer
      DNA insertional mutant that shows severe growth defects in early seedling growth,
      including delayed germination and cotyledon expansion, thinner yellow/pale-green
      leaves, and a slower growth rate. High-efficiency thermal asymmetric interlaced
      polymerase chain reaction analysis showed that the insertional locus was in the
      sixth exon of AT4G27490, encoding a predicted 3'-5'-exonuclease, that contained a
      conserved RNase phosphorolytic domain with high similarity to RRP41, designated
      RRP41L. Interestingly, we detected highly accumulated messenger RNAs (mRNAs) that
      encode seed storage protein and abscisic acid (ABA) biosynthesis and signaling
      pathway-related protein during the early growth stage in rrp41l mutants. The mRNA
      decay kinetics analysis for seed storage proteins, 9-cis-epoxycarotenoid
      dioxygenases, and ABA INSENSITIVEs revealed that RRP41L catalyzed the decay of
      these mRNAs in the cytoplasm. Consistent with these results, the rrp41l mutant
      was more sensitive to ABA in germination and root growth than wild-type plants,
      whereas overexpression lines of RRP41L were more resistant to ABA in germination
      and root growth than wild-type plants. RRP41L was localized to both the cytoplasm
      and nucleus, and RRP41L was preferentially expressed in seedlings. Altogether,
      our results showed that RRP41L plays an important role in seed germination and
      early seedling growth by mediating specific cytoplasmic mRNA decay in
      Arabidopsis.

PMID- 23132789
TI  - Hyptis pectinata: redox protection and orofacial antinociception.
AB  - Hyptis pectinata L. Poit, known as 'sambacaita', is used in Brazil to treat
      inflammatory and painful disorders. In this study, the antioxidant and orofacial
      antinociceptive properties of the aqueous extract of H. pectinata leaves (AEPH)
      were assessed using in vitro and in vivo models. Thus, AEPH reduced the 2,2
      diphenyl-1-picrylhydrazyl radical up to 72.10% with an EC50 of 14.56 ug/ml. It
      also inhibited 40.80% of the lipoperoxidation induced by 2'-azobis (2
      amidinopropane) dihydrochloride in the thiobarbituric acid-reactive substances
      assay. The orofacial antinociceptive activity was evaluated in mice pre-treated
      with AEPH (100, 200 and 400 mg/kg, p.o.) and morphine (5 mg/kg, i.p.), which
      received afterwards formalin- (20 ul, 2% solution, s.c.), glutamate- (40 ul, 25
      mM, s.c.) and capsaicin- (20 ul, 2.5 ug, s.c.) to induce orofacial nociception.
      AEPH at all doses reduced (p < 0.001) the nociceptive response in the first (43
      62%) and second (47-80%) phases of the formalin test. Besides, the effect of AEPH
      (400 mg/kg) was not changed in the presence of naloxone (1.5 mg/kg, i.p.), an
      opioid antagonist. AEPH significantly inhibited mice face rubbing for capsaicin
      (23-69%, p < 0.05) and glutamate (48-77%, p < 0.001) at all doses. The findings
      suggested the AEPH has peripheral and central antinociceptive activities, which
      are not related to opioid receptors.

PMID- 23132790
TI  - DUSP6/MKP3 is overexpressed in papillary and poorly differentiated thyroid
      carcinoma and contributes to neoplastic properties of thyroid cancer cells.
AB  - Thyroid carcinomas derived from follicular cells comprise papillary thyroid
      carcinoma (PTC), follicular thyroid carcinoma, poorly differentiated thyroid
      carcinoma (PDTC) and undifferentiated anaplastic thyroid carcinoma (ATC). PTC,
      the most frequent thyroid carcinoma histotype, is associated with gene
      rearrangements that generate RET/PTC and TRK oncogenes and with BRAF-V600E and
      RAS gene mutations. These last two genetic lesions are also present in a fraction
      of PDTCs. The ERK1/2 pathway, downstream of the known oncogenes activated in PTC,
      has a central role in thyroid carcinogenesis. In this study, we demonstrate that
      the BRAF-V600E, RET/PTC, and TRK oncogenes upregulate the ERK1/2 pathway's
      attenuator cytoplasmic dual-phase phosphatase DUSP6/MKP3 in thyroid cells. We
      also show DUSP6 overexpression at the mRNA and protein levels in all the analysed
      PTC cell lines. Furthermore, DUSP6 mRNA was significantly higher in PTC and PDTC
      in comparison with normal thyroid tissues both in expression profile datasets and
      in patients' surgical samples analysed by real-time RT-PCR. Immunohistochemical
      and western blot analyses showed that DUSP6 was also overexpressed at the protein
      level in most PTC and PDTC surgical samples tested, but not in ATC, and revealed
      a positive correlation trend with ERK1/2 pathway activation. Finally, DUSP6
      silencing reduced the neoplastic properties of four PTC cell lines, thus
      suggesting that DUSP6 may have a pro-tumorigenic role in thyroid carcinogenesis.

PMID- 23132791
TI  - STX2171, a 17beta-hydroxysteroid dehydrogenase type 3 inhibitor, is efficacious
      in vivo in a novel hormone-dependent prostate cancer model.
AB  - 17beta-Hydroxysteroid dehydrogenases (17beta-HSDs) catalyse the 17-position
      reduction/oxidation of steroids. 17beta-HSD type 3 (17beta-HSD3) catalyses the
      reduction of the weakly androgenic androstenedione (adione) to testosterone,
      suggesting that specific inhibitors of 17beta-HSD3 may have a role in the
      treatment of hormone-dependent prostate cancer and benign prostate hyperplasia.
      STX2171 is a novel selective non-steroidal 17beta-HSD3 inhibitor with an IC(50)
      of ~200 nM in a whole-cell assay. It inhibits adione-stimulated proliferation of
      17beta-HSD3-expressing androgen receptor-positive LNCaP(HSD3) prostate cancer
      cells in vitro. An androgen-stimulated LNCaP(HSD3) xenograft proof-of-concept
      model was developed to study the efficacies of STX2171 and a more established
      17beta-HSD3 inhibitor, STX1383 (SCH-451659, Schering-Plough), in vivo. Castrated
      male MF-1 mice were inoculated s.c. with 1*10(7) cells 24 h after an initial
      daily dose of testosterone propionate (TP) or vehicle. After 4 weeks, tumours had
      not developed in vehicle-dosed mice, but were present in 50% of those mice given
      TP. One week after switching the stimulus to adione, mice were dosed additionally
      with the vehicle or inhibitor for a further 4 weeks. Both TP and adione
      efficiently stimulated tumour growth and increased plasma testosterone levels;
      however, in the presence of either 17beta-HSD3 inhibitor, adione-dependent tumour
      growth was significantly inhibited and plasma testosterone levels reduced. Mouse
      body weights were unaffected. Both inhibitors also significantly lowered plasma
      testosterone levels in intact mice. In conclusion, STX2171 and STX1383
      significantly lower plasma testosterone levels and inhibit androgen-dependent
      tumour growth in vivo, indicating that 17beta-HSD3 inhibitors may have
      application in the treatment of hormone-dependent prostate cancer.

PMID- 23132793
TI  - Are we ready to modify the Bethesda thyroid fine-needle aspiration classification
      scheme?

PMID- 23132792
TI  - Impact of lymph node metastases identified on central neck dissection (CND) on
      the recurrence of papillary thyroid cancer: potential role of BRAFV600E mutation
      in defining CND.
AB  - The impact of metastasized cervical lymph nodes (CLN) identified on central neck
      dissection (CND) on the recurrence/persistence of papillary thyroid cancer (PTC)
      and the extent of CND needed to reduce recurrence/persistence have not been
      firmly established. To assess the impact of CLN metastasis and BRAF mutation on
      the recurrence/persistence of PTC and the potential of BRAF mutation in assisting
      CND. Analyses of 379 consecutive patients with PTC who underwent thyroidectomy
      with (n=243) or without CND (n=136) at a tertiary-care academic hospital during
      the period 2001-2010 for their clinicopathological outcomes and BRAF mutation
      status. Increasingly aggressive tumor characteristics were found as the extent of
      CND was advanced following conventional risk criteria from non-CND to limited CND
      to formal CND. Disease recurrence/persistence rate also sharply rose from 4.7% to
      15.7% and 40.5% in these CND settings respectively (P<0.0001). CLN metastasis
      rate rose from 18.0 to 77.3% from limited CND to formal CND (P<0.0001). An
      increasing rate of BRAF mutation was also found from less to more extensive CND.
      A strong association of CLN metastasis and BRAF mutation with disease
      recurrence/persistence was revealed on Kaplan-Meier analysis and BRAF mutation
      strongly predicted CLN metastasis. CLN metastases found on CND are closely
      associated with disease recurrence/persistence of PTC, which are both strongly
      predicted by BRAF mutation. Current selection of PTC patients for CND is
      appropriate but higher extent of the procedure, once selected, is needed to
      reduce disease recurrence, which may be defined by combination use of
      preoperative BRAF mutation testing and conventional risk factors of PTC.

PMID- 23132794
TI  - Brief report: self-organizing neuroepithelium from human pluripotent stem cells
      facilitates derivation of photoreceptors.
AB  - Retinitis pigmentosa, other inherited retinal diseases, and age-related macular
      degeneration lead to untreatable blindness because of the loss of photoreceptors.
      We have recently shown that transplantation of mouse photoreceptors can result in
      improved vision. It is therefore timely to develop protocols for efficient
      derivation of photoreceptors from human pluripotent stem (hPS) cells. Current
      methods for photoreceptor derivation from hPS cells require long periods of
      culture and are rather inefficient. Here, we report that formation of a transient
      self-organized neuroepithelium from human embryonic stem cells cultured together
      with extracellular matrix is sufficient to induce a rapid conversion into retinal
      progenitors in 5 days. These retinal progenitors have the ability to
      differentiate very efficiently into Crx(+) photoreceptor precursors after only 10
      days and subsequently acquire rod photoreceptor identity within 4 weeks. Directed
      differentiation into photoreceptors using this protocol is also possible with
      human-induced pluripotent stem (hiPS) cells, facilitating the use of patient
      specific hiPS cell lines for regenerative medicine and disease modeling.

PMID- 23132795
TI  - Al2O3 nanoparticles induce mitochondria-mediated cell death and upregulate the
      expression of signaling genes in human mesenchymal stem cells.
AB  - An increase in the broad usage of Al2O3 nanoparticles (ANPs) in the food and
      agricultural sectors may produce rare hazards for human health. The objective of
      this study was to assess the acute toxicity of ANPs in human mesenchymal stem
      cells (hMSCs) in vitro. Cell viability, cellular uptake, morphology, and gene
      expression using quantitative real-time polymerase chain reaction (qRT-PCR) were
      analyzed. The results indicate that ANPs have a significant and dose-dependent
      effect on cytotoxicity. Control cells showed a characteristic, homogeneous
      nuclear staining pattern, whereas ANP-exposed cells showed abnormal nuclear
      morphological changes such as condensation or fragmentation. An early
      characteristic of apoptosis was observed in ANP-treated cells. Further
      confirmation of cell death in hMSCs was observed through increased expression of
      chosen signaling genes and also decreased expression of Bcl-2 during mitochondria
      mediated cell death. Although they provide great advantages in food and
      agricultural products, the chronic and acute toxicity of ANPs still needs to be
      assessed carefully.

PMID- 23132796
TI  - Five-year incidence and postoperative visual outcome of cataract surgery in urban
      southern China: the Liwan Eye Study.
AB  - PURPOSE: To determine the 5-year incidence and visual outcome of cataract surgery
      in an adult urban Chinese population. METHODS: A comprehensive eye examination
      was performed at baseline and 5 years later on subjects participating in a
      population-based study. Incident cataract surgery was defined as having undergone
      surgery in either eye during the 5-year period. Postoperative visual impairment
      (PVI) was defined as visual acuity (VA) <6/18 based on both presenting VA (PVA)
      and best corrected VA (BCVA) in the operated eye. RESULTS: Among the 1405
      baseline participants, 75% (924) of survivors were seen at the 5-year follow-up
      visit. Forty-four returning participants (62 eyes) had undergone incident
      cataract surgery, an incidence of 4.84% (95% confidence interval [CI] = [3.53,
      6.44]). Detailed medical and surgical records were available for 54/62 (87.1%)
      eyes, and of these, 5/54 (24.1%) had an immediate preoperative visual acuity <=
      6/120. All recorded surgeries were performed at tertiary-level hospitals with
      phacoemulsification and foldable intraocular lens implantation. Those undergoing
      cataract surgery were more educated (P < 0.05) and had poorer baseline PVA in the
      worse-seeing eye (P < 0.001) than 54 persons with baseline PVA <6/18 due to
      cataract who had not had surgery. Among the 62 operated eyes, 22.6% (14/62) had
      PVI based on PVA and 9.6% (6/62) based on BCVA. CONCLUSIONS: Despite somewhat
      lower incidence, outcomes of cataract surgery in urban southern China are
      comparable with developed countries and better than for rural China. In urban
      China, emphasis should be on improving access to surgery.

PMID- 23132797
TI  - Elevated levels of monocyte chemoattractant protein-1 in the aqueous humor after
      phacoemulsification.
AB  - PURPOSE: To elucidate the impact of phacoemulsification on aqueous monocyte
      chemoattractant protein-1 (MCP-1) levels, and identify its cell origin. METHODS:
      For clinical study, aqueous humor samples were collected before and after surgery
      (17.0 +/- 4.0 months postoperatively) from 21 cataract cases that underwent
      phacoemulsification and intraocular lens (IOL) implantation. Aqueous MCP-1 levels
      were determined using a multiplex immunoassay. For animal experiments, rabbits
      underwent phacoemulsification (+/- IOL). Aqueous humor samples were collected
      from nonoperated eyes and operated eyes, and immunoassays were performed. Eyes
      were analyzed by reverse transcription-polymerase chain reaction and
      immunohistochemical studies. RESULTS: In the clinical study, mean (+/- SD)
      aqueous MCP-1 levels were higher postoperatively (1773.5 +/- 321.2 pg/mL) than
      preoperatively (796.9 +/- 211.3 pg/mL; P < 0.0001). In animal experiments, mean
      aqueous MCP-1 levels (pg/mL) were higher in postoperative eyes on day 30 (207.1
      +/- 62.9) than in nonoperated eyes (31.2 +/- 12.5; P = 0.018). IOL implantation
      did not affect the changes in MCP-1 levels. After phacoemulsification, MCP-1 mRNA
      expression was increased in the cornea, iris, ciliary body, and capsular bag.
      Expression of MCP-1 mRNA in the capsular bag, but not the other tissues,
      increased from day 30 to 90. Immunohistochemical studies showed positive
      immunoreactivity for MCP-1 in cells of the posterior capsule after
      phacoemulsification. CONCLUSIONS: aqueous MCP-1 levels were elevated in both
      human and animal eyes after phacoemulsification. Proliferated Lens epithelial
      cells on the capsule might be the major cell origin for prolonged MCP-1
      production after phacoemulsification. (http://www.umin.ac.jp/ number,
      UMIN000005788.).

PMID- 23132798
TI  - Metallothionein-III deficiency exacerbates light-induced retinal degeneration.
AB  - PURPOSE: Retinal photoreceptor damage is a common feature of ophthalmic
      disorders, such as age-related macular degeneration and retinitis pigmentosa.
      Oxidative stress has a key role in these diseases. Metallothioneins (MTs) are a
      family of cysteine-rich proteins, and various physiologic functions have been
      reported, including protection against metal toxicity and antioxidative potency.
      We investigated the functional role of MT-III in light-induced retinal damage.
      METHODS: The expression of retinal MT-I, -II, and -III mRNA was evaluated by real
      time reverse-transcription PCR in retina exposed to light. Retinal damage in MT
      deficient mice was induced by exposure to white light at 16,000 lux for 3 hours
      after dark adaptation. Photoreceptor damage was evaluated histologically by
      measuring the thickness of the outer nuclear layer (ONL) 5 days after light
      exposure and by electroretinogram recording. In an in vitro experiment, the MT
      III siRNAs were tested for their effects on light-induced mouse photoreceptor
      cell (661W) damage. RESULTS: The mRNAs of the MTs were increased significantly in
      murine retina after light exposure. The ONL in the MT-III-deficient mice was
      remarkably thinner compared to light-exposed wild-type (WT) mice, and a- and b
      wave amplitudes were decreased; the damage induced in MT-I/-II-deficient mice was
      comparable to that observed in WT mice. MT-III knockdown by siRNA in 661W
      exacerbated the cell damage and increased the production of reactive oxygen
      species in response to light exposure. CONCLUSIONS: These findings suggested that
      MT-III can help protect against light-induced retinal damage compared to MT-I/II.
      Some of these effects may be exerted by its antioxidative potency.

PMID- 23132799
TI  - Activity limitation due to a fear of falling in older adults with eye disease.
AB  - PURPOSE: To examine whether patients with age-related macular degeneration (AMD),
      glaucoma, or Fuchs corneal dystrophy report limiting their activity due to a fear
      of falling as compared with a control group of older adults with good vision.
      METHODS: We recruited 345 patients (93 with AMD, 57 with Fuchs, 98 with glaucoma,
      and 97 controls) from the ophthalmology clinics of Maisonneuve-Rosemont Hospital
      (Montreal, Canada) to participate in a cross-sectional study from September 2009
      until July 2012. Control patients who had normal visual acuity and visual field
      were recruited from the same clinics. Participants were asked if they limited
      their activity due to a fear of falling. Visual acuity, contrast sensitivity, and
      visual field were measured and the medical record was reviewed. RESULTS: Between
      40% and 50% of patients with eye disease reported activity limitation due to a
      fear of falling compared with only 16% of controls with normal vision. After
      adjustment for age, sex, race, number of comorbidities, cognition, and lens
      opacity, the Fuchs groups was most likely to report activity limitation due to a
      fear of falling (odds ratio [OR] = 3.07; 95% confidence interval [CI], 1.33-7.06)
      followed by the glaucoma group (OR = 2.84; 95% CI, 1.36-5.96) and the AMD group
      (OR = 2.42; 95% CI, 1.09-5.35). Contrast sensitivity best explained these
      associations. CONCLUSIONS: Activity limitation due to a fear of falling is very
      common in older adults with visually impairing eye disease. Although this
      compensatory strategy may protect against falls, it may also put people at risk
      for social isolation and disability.

PMID- 23132800
TI  - The impact of macular pigment augmentation on visual performance using different
      carotenoid formulations.
AB  - PURPOSE: To investigate changes in macular pigment optical density (MPOD) and
      visual performance following supplementation with different macular carotenoid
      formulations. METHODS: Thirty-six subjects (19 male, 17 female; mean SD, age 51
      13 years) were recruited into this single-masked placebo-controlled study, and
      were randomly assigned to one of the following three intervention
      (supplementation) groups: (1) group 1 (20 mg lutein [L] and 2 mg zeaxanthin [Z]);
      (2) group 2 (10 mg L, 2 mg Z, and 10 mg meso-zeaxanthin [MZ]); and group 3
      (placebo). Outcomes measures included visual performance and MPOD response. Data
      were collected at baseline, at 3 months, and at 6 months. RESULTS: At 3 and 6
      months, a statistically significant increase in MPOD was found at all
      eccentricities (other than the most peripheral 3 degrees  location) in group 2 (P
      < 0.05 for all), whereas no significant increase in MPOD was demonstrable at any
      eccentricity for subjects in groups 1 and 3. Statistically significant
      improvements in visual performance measures including visual acuity and contrast
      sensitivity with and without glare were observed for group 2 only. Only mesopic
      contrast sensitivity at one spatial frequency improved significantly by 6 months
      (P < 0.05) for group 1. No improvements in any parameters of visual performance
      were observed for subjects supplemented with placebo (P > 0.05 for all).
      CONCLUSIONS: These results suggest that supplementation with all three macular
      carotenoids potentially offered advantages over preparations lacking MZ, both in
      terms of MPOD response and visual performance enhancement.

PMID- 23132801
TI  - Ectopic epithelial implants following surface ablation of the cornea.
AB  - PURPOSE: To determine the direct contribution of the epithelium to the generation
      of complications using a phototherapeutic keratectomy model. METHODS: A mouse
      model with a genetically labeled epithelium was used to determine whether any
      epithelium-derived cells persist in the stroma up to 1 month after surgery. Also,
      gross histology and macrophotography of excimer-ablated rabbit corneas were
      analyzed for evidence epithelial ingrowths into the stroma. RESULTS: Epithelium
      derived cells were present in the wounded stroma 1 month after surgery.
      Micrographs taken during the first 4 days during healing evidenced epithelial
      invasion of the stroma in one and sometimes more locations in the same cornea.
      Gross histology also revealed that the epithelial invasions can result in
      complete delamination of stromal tissue and subsequent inclusion of the stromal
      material in the epithelium. The epithelial inclusions ultimately created a highly
      irregular corneal surface. CONCLUSIONS: Ectopic epithelia are a known
      complication of LASIK and LASIK-like procedures. The data presented here indicate
      that ectopic epithelia are also a complication of surface ablation techniques.
      The knowledge that these complications are present following surface ablations
      provides a new understanding of the biological response to surface ablation
      techniques and suggests new avenues of study to improve clinical outcomes of
      those for whom LASIK-based techniques are not an option.

PMID- 23132802
TI  - Short-term effects of extremely low frequency pulsed electromagnetic field on
      corneas with alkaline burns in rabbits.
AB  - PURPOSE: To investigate the short-term effects of extremely low frequency pulsed
      electromagnetic fields (ELF-PEMF) on the healing of alkaline-burned corneas in
      rabbits. METHODS: Fifty-six alkaline-burned corneas from 56 rabbits were
      categorized into four groups: ELF-PEMF therapy with 2 mTesla (mT) intensity (ELF
      2) for 30 minutes twice daily, ELF-PEMF therapy with 5 mT intensity (ELF 5) for
      30 minutes twice daily, medical therapy (MT), and controls. Clinical examination
      together with digital photography of the corneas was performed on days 0, 2, 7,
      and 14. After euthanizing the rabbits, affected eyes were evaluated by way of
      histopathology. Finally the clinical and the histopathologic results of the four
      groups were compared. RESULTS: None of the cases developed limbal ischemia,
      symblepharon formation, Descemetocele, or corneal perforation. Although the area
      of corneal defect in the ELF groups on day 2 was significantly less than the
      defects in MT, it was not notably different from those on days 7 and 14. Rate of
      significant corneal neovascularization on days 7 and 14 was not statistically
      different between the groups. The keratocyte loss in MT was significantly higher
      than in the ELF groups. Mild stromal scar formation was observed more frequently
      in ELF-PEMF groups than the control. CONCLUSIONS: Short-term ELF-PEMF therapy is
      a safe, noninvasive, and markedly effective method in healing alkaline-burned
      corneas, and its therapeutic results are comparable with those of MT.

PMID- 23132804
TI  - Acanthamoeba-cytopathic protein induces apoptosis and proinflammatory cytokines
      in human corneal epithelial cells by cPLA2alpha activation.
AB  - PURPOSE: We have shown that Acanthamoeba interacts with a mannosylated protein on
      corneal epithelial cells and stimulates trophozoites to secrete a mannose-induced
      133 kDa protease (MIP-133), which facilitates corneal invasion and induces
      apoptosis. The mechanism of MIP-133-induced apoptosis is unknown. The aim of this
      study was to determine if MIP-133 induces apoptosis and proinflammatory
      cytokines/chemokines in human corneal epithelial (HCE) cells via the cytosolic
      phospholipase A(2alpha) (cPLA(2alpha)) pathway. METHODS: HCE cells were incubated
      with or without MIP-133 at doses of 7.5, 15, and 50 MUg/mL for 6, 12, and 24
      hours. The effects of cPLA(2alpha) inhibitors on cPLA(2alpha), arachidonic acid
      (AA) release, and apoptosis were tested in vitro. Inhibition of cPLA(2alpha)
      involved preincubating HCE cells for 1 hour with cPLA(2alpha) inhibitors (10 MUM
      methyl-arachidonyl fluorophosphonate [MAFP] or 20 MUM arachidonyl trifluoromethyl
      ketone [AACOCF3]) with or without MIP-133 for 24 hours. Expression of
      cPLA(2alpha) mRNA and enzyme was examined by RT-PCR and cPLA(2) activity assays,
      respectively. Apoptosis of corneal epithelial cells was determined by caspase-3
      and DNA fragmentation assays. Expression of IL-8, IL-6, IL-1beta, and IFN-gamma
      was examined by RT-PCR and ELISA. RESULTS: MIP-133 induced significant
      cPLA(2alpha) (approximately two to four times) and AA release (approximately six
      times) from corneal cells while cPLA(2alpha) inhibitors significantly reduced
      cPLA(2alpha) (approximately two to four times) and AA release (approximately
      three times) (P < 0.05). cPLA(2alpha) inhibitors significantly inhibited MIP-133
      induced DNA fragmentation approximately 7 to 12 times in HCE cells (P < 0.05).
      MIP-133 specifically activates cPLA(2alpha) enzyme activity in HCE cells, which
      is blocked by preincubation with anti-MIP-133 antibody. In addition, MIP-133
      induced significant IL-8, IL-6, IL-1beta, and IFN-gamma production, approximately
      two to three times (P < 0.05). CONCLUSIONS: MIP-133 interacts with phospholipids
      on plasma membrane of HCE cells and activates cPLA(2alpha). cPLA(2alpha) is
      involved in apoptosis, AA release, and activation of proinflammatory
      cytokines/chemokines from HCE cells. cPLA(2alpha) inhibitors may be a therapeutic
      target in Acanthamoeba keratitis.

PMID- 23132806
TI  - Crystallin-beta-b2-overexpressing NPCs support the survival of injured retinal
      ganglion cells and photoreceptors in rats.
AB  - PURPOSE: Crystallin beta-b2 (crybb2) is known to support the regeneration of
      retinal ganglion cell (RGC) axons in culture. We investigated whether neuronal
      progenitor cells (NPCs) overexpressing crybb2 (crybb2-NPC) affect secondary
      retinal degeneration due to optic nerve crush in vivo. METHODS: NPCS were
      produced by dissociation and propagation of rat embryonic neural tube and eye
      primordial cells at embryonic days 13.5 and 15. Retinal degeneration was induced
      by injured optic nerve crush (BY suture, 20 seconds). Several groups were built:
      crybb2-NPC were injected into the vitreous body, while the Controls were
      comprised of recombinant crybb2-injected and PBS-injected groups. The eyes, in
      particular the retina, were analyzed by immunohistochemistry and Western blotting
      for different antigens at 2 and 4 weeks after surgery. RESULTS: At 2 and 4 weeks
      post surgery, crybb2-NPC resided within the vitreoretinal compartment, and were
      persistently nestin-positive throughout the experimental period. The cells
      stained positive for various neurotrophins and acted as "living" cell factories
      to support the survival of injured RGCs. The crybb2-NPC migrated throughout the
      eye structures and sometimes became integrated within the tissue. Most of the
      ocular cells responded to the appearance of crybb2-NPC with marked changes of
      certain proteins, including Iba-1 (microglia), vimentin (glial cells), and
      rhodopsin (photoreceptors). Photoreceptors also displayed a better survival after
      crybb2-NPC injection compared to control groups. CONCLUSIONS: Crybb2-NPC exert
      beneficial effects on the vitreoretinal compartment, which suggests that modified
      crybb2-NPC could be used in a novel strategy for the treatment of degenerative
      vitreoretinal diseases. However, future studies must determine the safety of in
      vivo administration of crybb2-NPC.

PMID- 23132803
TI  - Retinal thickness in people with diabetes and minimal or no diabetic retinopathy:
      Heidelberg Spectralis optical coherence tomography.
AB  - PURPOSE: To evaluate macular thickness in people with diabetes but minimal or no
      retinopathy using Heidelberg Spectralis optical coherence tomography (OCT).
      METHODS: In a multicenter, cross-sectional study of mean retinal thickness, on
      Spectralis OCT in the nine standard OCT subfields, spanning a zone with 6-mm
      diameter, center point, and total retinal volume were evaluated. Central subfield
      (CSF) thickness was evaluated for association with demographic and clinical
      factors. Stratus OCT scans also were performed on each participant. RESULTS: The
      analysis included 122 eyes (122 participants) with diabetes and no (n = 103) or
      minimal diabetic retinopathy (n = 19) and no macular retinal thickening on
      clinical exam. Average CSF thickness was 270 +/- 24 MUm. Central subfield
      thickness was significantly greater in males relative to females (mean 278 +/- 23
      MUm vs. 262 +/- 22 MUm, P < 0.001). After adjusting for gender, no additional
      factors were found to be significantly associated with CSF thickness (P > 0.10).
      Mean Stratus OCT CSF thickness was 199 +/- 24 MUm. CONCLUSIONS: Mean CSF
      thickness is approximately 70 MUm thicker when measured with Heidelberg
      Spectralis OCT as compared with Stratus OCT among individuals with diabetes in
      the absence of retinopathy or with minimal nonproliferative retinopathy and a
      normal macular architecture. CSF thickness values >= 320 MUm for males and 305
      MUm for females (~2 SDs above the average for this normative cohort) are proposed
      as gender-specific thickness levels to have reasonable certainty that diabetic
      macular edema involving the CSF is present using Spectralis measurements.

PMID- 23132805
TI  - Corneal sulfated glycosaminoglycans and their effects on trigeminal nerve growth
      cone behavior in vitro: roles for ECM in cornea innervation.
AB  - PURPOSE: Sensory trigeminal nerve growth cones innervate the cornea in a highly
      coordinated fashion. The purpose of this study was to determine if extracellular
      matrix glycosaminoglycans (ECM-GAGs), including keratan sulfate (KS), dermatan
      sulfate (DS), and chondroitin sulfate A (CSA) and C (CSC), polymerized in
      developing eyefronts, may provide guidance cues to nerves during cornea
      innervation. METHODS: Immunostaining using antineuron-specific-beta-tubulin and
      monoclonal antibodies for KS, DS, and CSA/C was performed on eyefronts from
      embryonic day (E) 9 to E14 and staining visualized by confocal microscopy.
      Effects of purified GAGs on trigeminal nerve growth cone behavior were tested
      using in vitro neuronal explant cultures. RESULTS: At E9 to E10, nerves exiting
      the pericorneal nerve ring grew as tight fascicles, advancing straight toward the
      corneal stroma. In contrast, upon entering the stroma, nerves bifurcated
      repeatedly as they extended anteriorly toward the epithelium. KS was localized in
      the path of trigeminal nerves, whereas DS and CSA/C-rich areas were avoided by
      growth cones. When E10 trigeminal neurons were cultured on different substrates
      comprised of purified GAG molecules, their neurite growth cone behavior varied
      depending on GAG type, concentration, and mode of presentation (immobilized
      versus soluble). High concentrations of immobilized KS, DS, and CSA/C inhibited
      neurite growth to varying degrees. Neurites traversing lower, permissive
      concentrations of immobilized DS and CSA/C displayed increased fasciculation and
      decreased branching, whereas KS caused decreased fasciculation and increased
      branching. Enzymatic digestion of sulfated GAGs canceled their effects on
      trigeminal neurons. CONCLUSIONS: Data herein suggest that GAGs may direct the
      movement of trigeminal nerve growth cones innervating the cornea.

PMID- 23132807
TI  - 24-hour intraocular pressure of young healthy humans in supine position: rhythm
      and reproducibility.
AB  - PURPOSE: We evaluated the supine 24-hour IOP rhythm reproducibility over 6 weeks
      in healthy humans. METHODS: Six healthy young male subjects underwent six 24-hour
      sessions of IOP measurements over a 6-week period. Subjects were housed in a
      sleep laboratory in a constant controlled supine position and in a strictly
      controlled environment. IOP was measured hourly using a pneumatonometer. A
      nonlinear least-squares dual harmonic regression analysis was used to model the
      24-hour IOP rhythm. The intra- and intersubject variability of acrophase,
      bathyphase, amplitude, and IOP values were evaluated. RESULTS: A significant
      nyctohemeral IOP rhythm was noted in 30 of 36 (83%) sessions. Mean nocturnal IOP
      was significantly higher than diurnal IOP (20.1 0.2 MM HG [SD] VS. 18.8 0.1 MM
      HG, P 0.001) in all subjects. Amplitudes were not statistically different among
      subjects (P = 0.52). IN contrast, acrophase and bathyphase were statistically
      different (P 0.05). Intrasubject homogeneity of distribution over time of the
      acrophase and bathyphase was significant in 3 of 6 and 4 of 6 subjects,
      respectively. Intraclass correlation coefficients of midline estimating statistic
      of rhythm (MESOR) and IOP values AT 2: 00, 3:00, 4:00, 10:00, and 11:00 AM, and
      2:00 PM showed fair to good agreement among sessions. CONCLUSIONS: In a constant
      supine position, all subjects exhibited a nyctohemeral IOP rhythm present at an
      average rate of 80% of all sessions. With the currently available methods of
      tonometry, intrasubject reproducibility of rhythmic parameters and IOP values is
      limited. IOP values in the morning and IOP MESOR were the most reproducible
      parameters among the six visits.

PMID- 23132808
TI  - Effects of methyl and isopropyl N-methylanthranilates from Choisya ternata Kunth
      (Rutaceae) on experimental anxiety and depression in mice.
AB  - Choisya ternata Kunth (Rutaceae) is a plant species used in Mexican folk medicine
      for its antispasmodic and simulative properties. Recently, we identified a new
      alkaloid, isopropyl N-methylanthranilate, and a related one, methyl N
      methylanthranilate, from the essential oil of this species and have proven them
      to possess antinociceptive activity even at 0.3 mg/kg. In the present study,
      anxiolytic and antidepressant effects of the two compounds have been studied in
      open field, horizontal wire, light/dark, forced swimming and tail suspension
      tests, as well as the effect on the onset and duration of diazepam-induced sleep
      in BALB/c mice. The volatile alkaloids (50-200 mg/kg, administered
      intraperitoneally), without having a muscle relaxant effect, caused a significant
      increase in the time the animals spent in an unsecured and putatively dangerous
      area when compared with the control group but had no effect on the number of
      crossings between the light/dark compartments. In addition to this anxiolytic
      activity, a significantly antidepressant-like effect was apparent at all tested
      doses, which was not due to an increase in locomotive activity. The anthranilates
      administered on their own did not induce sleep in mice but significantly
      prolonged the diazepam-induced sleep, in a dose-dependent way, suggesting an
      interaction with the gamma-aminobutyric acid receptor complex.

PMID- 23132809
TI  - Can changing the terminology for benign aspirates reduce the atypia of
      undetermined significance/follicular lesion of undetermined significance rate in
      thyroid fine-needle aspirates?

PMID- 23132810
TI  - Concise review: genetically engineered stem cell therapy targeting angiogenesis
      and tumor stroma in gastrointestinal malignancy.
AB  - Cell-based gene therapy holds considerable promise for the treatment of human
      malignancy. Genetically engineered cells if delivered to sites of disease could
      alleviate symptoms or even cure cancer through expression of therapeutic or
      suicide transgene products. Mesenchymal stem cells (MSCs), nonhematopoietic
      multipotent cells found primarily in bone marrow, have garnered particular
      interest as potential tumor-targeting vehicles due to their innate tumortropic
      homing properties. However, recent strategies go further than simply using MSCs
      as vehicles and use the stem cell-specific genetic make-up to restrict transgene
      expression to tumorigenic environments using tumor-tissue specific promoters.
      This addresses one of the concerns with this novel therapy that nonselective stem
      cell-based therapy could induce cancer rather than treat it. Even minimal off
      target effects can be deleterious, motivating recent strategies to not only
      enhance MSC homing but also engineer them to make their antitumor effect
      selective to sites of malignancy. This review will summarize the advances made in
      the past decade toward developing novel cell-based cancer therapies using
      genetically engineered MSCs with a focus on strategies to achieve and enhance
      tumor specificity and their application to targeting gastrointestinal
      malignancies such as hepatocellular carcinoma and pancreatic adenocarcinoma.

PMID- 23132811
TI  - Dietary antioxidant, quercetin, protects sertoli-germ cell coculture from
      atrazine-induced oxidative damage.
AB  - Quercetin (QT), a dietary-derived flavonoid, is ubiquitous in fruits and
      vegetables and plays an important role in human health by virtue of its
      antioxidant function. The present study was designed to examine the effects of QT
      on oxidative damage that was induced by the herbicide, atrazine (ATZ), in mixed
      cultures of Sertoli-germ cells. Results showed that treatment with QT increased
      cell viability and decreased catalase activity, malondialdehyde, and reactive
      oxygen species (ROS) levels. QT treatment also increased the mRNA expression of
      glutathione peroxidase (GSH-Px), glutathione reductase (GR), glutathione-S
      transferase, and superoxide dismutase-1 and could not reversed to the control
      levels ATZ-induced steady-state mRNA levels of these antioxidant genes as well as
      the level of glutathione and activities of GSH-Px and GR. QT has protective
      effect against ATZ-induced oxidative stress through a reduction in ROS levels and
      lipid peroxidation.

PMID- 23132812
TI  - Changes in tobacco industry advertising around high schools in Greece following
      an outdoor advertising ban: a follow-up study.
AB  - BACKGROUND: As tobacco advertising bans are enacted in accordance with the
      Framework Convention on Tobacco Control, it is essential to assess enforcement
      and how the industry may circumvent such measures. OBJECTIVE DESIGN: During this
      longitudinal study, we compared the characteristics of points-of-sale (POS)
      advertising within 300 m of all high schools in Heraklion, Greece before (n=101
      POS and 44 billboards in 2007) and after (n=106 POS in 2011) an outdoor
      advertising ban was implemented in 2009. Cigarette advertisements in all
      retailers near all high schools were assessed. RESULTS: Following the ban,
      tobacco industry billboards around schools were eradicated (from 44 to 0). The
      proportion of POS that had external advertisements dropped from 98% to 66%
      (p<0.001), more so in regulated convenience stores (from 97% to 35%, p<0.001)
      than in kiosks (98% to 92%, p=0.192), which were exempt from the ban. The
      proportion of convenience stores that had advertisements on the door (79.5% to
      20.4%, p<0.001), ads that could be seen from the street (92.3% to 22.4%, p<0.001)
      or illuminated exterior ads (46.2% to 10.2%, p<0.001) was also significantly
      reduced. Overall, the average number of exterior advertisements per POS fell from
      7.4 to 3.9 (p<0.05). This reduction was noted in regulated convenience stores
      (4.8+/-3.0 vs 0.9+/-2.1, p<0.001) and in unregulated kiosks (9.0+/-6.7 vs 6.5+/
      4.5, p=0.019). CONCLUSIONS: The outdoor advertising restriction in Greece has led
      to a reduced number of tobacco advertisements per POS, and the eradication of
      billboard advertising. Nevertheless, there is a need to regulate kiosks, which
      were identified as a key vector for tobacco advertising, and to increase
      compliance among regulated convenience stores.

PMID- 23132813
TI  - Neoplasm prevention and immuno-enhancement mediated by daily consumption of a
      proprietary extract from North American ginseng by elderly mice of a cancer-prone
      strain.
AB  - Cells belonging to the innate immune system, known as natural killer (NK) cells,
      act as the first line of defense against developing neoplasms. We have previously
      shown in a leukemia-induced tumor model (mouse) that a proprietary extract (CVT
      E002), of North American ginseng, administered in the diet, significantly
      increased the absolute numbers of NK cells, significantly decreased leukemia
      cells and significantly increased the life span of CVT-E002-fed leukemic mice. In
      the present study, we assessed the efficacy of this extract to inhibit the
      spontaneous development of tumors in elderly mice of the cancer-prone C3H strain.
      Dietary CVT-E002 was fed for approximately a year beginning when mice were almost
      2 years of age. Control mice, consuming the same chow without CVT-E002, all
      developed assorted, palpable tumors between 22 and 33 months, while all mice
      consuming CVT-E002 remained alive and tumor-free until they were purposely
      euthanized as healthy animals. The absolute numbers of NK cells at euthanasia, in
      CVT-E002-consuming mice, were significantly elevated in both the spleen and bone
      marrow. Given these profoundly positive results and the fact that CVT-E002
      already exists in the marketplace under the label Cold-fX(r), the potential for
      cancer prevention in humans becomes apparent.

PMID- 23132814
TI  - Musashi1-CreER(T2) : a new cre line for conditional mutagenesis in neural stem
      cells.
AB  - The RNA-binding protein Musashi1 (Msi1) is one of two mammalian homologues of
      Drosophila Musashi, which is required for the asymmetric cell division of sensory
      organ precursor cells. In the mouse central nervous system (CNS), Msi1 is
      preferentially expressed in mitotically active progenitor cells in the
      ventricular zone (VZ) of the neural tube during embryonic development and in the
      subventricular zone (SVZ) of the postnatal brain. Previous studies showed that
      cells in the SVZ can contribute to long-term neurogenesis in the olfactory bulb
      (OB), but it remains unclear whether Msi1-expressing cells have self-renewing
      potential and can contribute to neurogenesis in the adult. Here, we describe the
      generation of Msi1-CreER(T2) knock-in mice and show by cell lineage tracing that
      Msi1-CreER(T2) -expressing cells mark neural stem cells (NSCs) in both the
      embryonic and adult brain. Msi1-CreER(T2) mice thus represent a new tool in our
      arsenal for genetically manipulating NSCs, which will be essential for
      understanding the molecular mechanisms underlying neural development.

PMID- 23132815
TI  - A Synthetic Comparator Approach to Local Evaluation of School-Based Substance Use
      Prevention Programming.
AB  - We propose a method for creating groups against which outcomes of local pretest
      posttest evaluations of evidence-based programs can be judged. This involves
      assessing pretest markers for new and previously conducted evaluations to
      identify groups that have high pretest similarity. A database of 802 prior local
      evaluations provided six summary measures for analysis. The proximity of all
      groups using these variables is calculated as standardized proximities having
      values between 0 and 1. Five methods for creating standardized proximities are
      demonstrated. The approach allows proximity limits to be adjusted to find
      sufficient numbers of synthetic comparators. Several index cases are examined to
      assess the numbers of groups available to serve as comparators. Results show that
      most local evaluations would have sufficient numbers of comparators available for
      estimating program effects. This method holds promise as a tool for local
      evaluations to estimate relative effectiveness. 

PMID- 23132817
TI  - Prospective analysis of atypical epithelial cells as a high-risk cytologic
      feature for malignancy in pancreatic cysts.
AB  - BACKGROUND: Pancreatic cysts are aspirated to assess whether a cyst is mucinous
      on one hand and malignant on the other. The authors' retrospective data have
      indicated that high-grade atypical epithelial cells (AECs) identified on cytology
      are a high-risk feature and a better threshold than "positive" for detecting
      malignancy. The objective of the current study was to assess the accuracy of AECs
      in predicting malignancy in pancreatic cysts. METHODS: Cysts aspirated by
      endoscopic ultrasound (EUS)-guided fine-needle aspiration (EUS-FNAs) obtained
      between January 2006 and June 2011 were evaluated. Cytologic, histologic,
      imaging, and cyst fluid analysis data were recorded. AECs were defined as cells
      that had an increased nuclear-to-cytoplasmic ratio and nuclear hyperchromasia
      with or without membrane abnormalities and with or without cytoplasmic vacuoles,
      but of insufficient quality and quantity for a "positive" interpretation.
      Malignancy included mucinous cysts with high-grade dysplasia and invasive
      carcinoma. Performance characteristics of cytology with AECs or worse (high-grade
      atypia [HGA]) for predicting malignancy were assessed. RESULTS: There were 70
      FNAs that had histologic confirmation from 404 EUS-FNAs in 352 patients.
      Excluding 4 nondiagnostic FNAs, the study cohort consisted of 66 FNAs for
      analysis. There were 24 malignant cysts with 20 true-positive, 4 false-negative,
      36 true-negative, and 6 false-positive results. For the detection of malignancy,
      HGA had 83% sensitivity, 86% specificity, a positive predictive value of 77%, a
      negative predictive value of 90%, and 85% overall accuracy. The lower threshold
      for malignancy with AECs resulted in a 12% increase in the detection of
      malignancy. CONCLUSIONS: A finding of AECs on cytology is a high-risk feature for
      malignancy and is an accurate triage threshold for resection. Cancer (Cancer
      Cytopathol) 2013;121:29-36 (c) 2012 American Cancer Society.

PMID- 23132816
TI  - Mesenchymal stromal cells improve survival during sepsis in the absence of heme
      oxygenase-1: the importance of neutrophils.
AB  - The use of mesenchymal stromal cells (MSCs) for treatment of bacterial
      infections, including systemic processes like sepsis, is an evolving field of
      investigation. This study was designed to investigate the potential use of MSCs,
      harvested from compact bone, and their interactions with the innate immune
      system, during polymicrobial sepsis induced by cecal ligation and puncture (CLP).
      We also wanted to elucidate the role of endogenous heme oxygenase (HO)-1 in MSCs
      during a systemic bacterial infection. MSCs harvested from the bones of HO-1
      deficient (-/-) and wild-type (+/+) mice improved the survival of HO-1(-/-) and
      HO-1(+/+) recipient mice when administered after the onset of polymicrobial
      sepsis induced by CLP, compared with the administration of fibroblast control
      cells. The MSCs, originating from compact bone in mice, enhanced the ability of
      neutrophils to phagocytize bacteria in vitro and in vivo and to promote bacterial
      clearance in the peritoneum and blood after CLP. Moreover, after depleting
      neutrophils in recipient mice, the beneficial effects of MSCs were entirely lost,
      demonstrating the importance of neutrophils for this MSC response. MSCs also
      decreased multiple organ injury in susceptible HO-1(-/-) mice, when administered
      after the onset of sepsis. Taken together, these data demonstrate that the
      beneficial effects of treatment with MSCs after the onset of polymicrobial sepsis
      is not dependent on endogenous HO-1 expression, and that neutrophils are crucial
      for this therapeutic response.

PMID- 23132818
TI  - Acute effects of pyrethroids on serotonin release in the striatum of awake rats:
      an in vivo microdialysis study.
AB  - The present study examined the acute neurotoxic effects of three different
      pyrethroids, allethrin, cyhalothrin, and deltamethrin on the release of serotonin
      (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the striatum of
      conscious rats using microdialysis. Allethrin 10 mg/kg reduced extracellular
      levels of 5-HT to 46%, whereas 20 and 60 mg/kg increased the release to 177% and
      243% of baseline, respectively. Cyhalothrin increased 5-HT release to 145-204%
      and deltamethrin decreased to 58-32% of baseline in a dose-dependent manner. None
      of the pyrethroids tested altered extracellular levels of 5-HIAA. Local infusion
      of the voltage-gated sodium channel antagonist tetrodotoxin (TTX) into striatum
      completely prevented the effects of allethrin, cyhalothrin, and deltamethrin (10
      and 20 mg/kg) on 5-HT release. The effect of deltamethrin at 60 mg/kg was
      completely abolished by striatal infusion of nimodipine (L-type Ca++ channel
      antagonist) with TTX. These findings suggest that pyrethroids disrupt the
      serotonergic neurotransmission in striatum in a dose-related manner with Na+ and
      Ca2+ channel-dependent mechanisms.

PMID- 23132819
TI  - Effects of treatment differences on psychosocial predictors of exercise and
      improved eating in obese, middle-age adults.
AB  - BACKGROUND: Behavioral interventions for weight-loss have been largely
      unsuccessful. Exercise is the strongest predictor of maintained weight loss and
      much of its effects may be from associated changes in psychosocial factors.
      METHODS: Middle-aged, formerly sedentary adults with severe obesity were randomly
      selected to 6-month treatments of cognitive-behavioral exercise support paired
      with either standard nutrition education (n = 99) or nutrition change supported
      by cognitive-behavioral means with an emphasis on self-regulation (n = 101).
      RESULTS: Overall improvements in self-efficacy and self-regulation for both
      exercise and managed eating, and mood, were found, with significantly greater
      improvements associated with the cognitive-behavioral nutrition condition in self
      regulation for eating and mood. Change scores trended toward being stronger
      predictors of increased exercise and fruit and vegetable intake than scores at
      treatment end. Multiple regression analyses indicated that significant portions
      of the variance in both increased volume of exercise (R2 = 0.45) and fruit and
      vegetable intake (R2 = 0.21) were explained by changes in self-regulatory skill
      usage, self-efficacy, and mood. CONCLUSIONS: Cognitive-behavioral methods for
      improved eating paired with behavioral support of exercise may improve weight
      loss through effects on the psychosocial factors of self-regulation, self
      efficacy, and overall mood more than when standard nutrition education is
      incorporated.

PMID- 23132820
TI  - Cell surface structures influence lung clearance rate of systemically infused
      mesenchymal stromal cells.
AB  - The promising clinical effects of mesenchymal stromal/stem cells (MSCs) rely
      especially on paracrine and nonimmunogenic mechanisms. Delivery routes are
      essential for the efficacy of cell therapy and systemic delivery by infusion is
      the obvious goal for many forms of MSC therapy. Lung adhesion of MSCs might,
      however, be a major obstacle yet to overcome. Current knowledge does not allow us
      to make sound conclusions whether MSC lung entrapment is harmful or beneficial,
      and thus we wanted to explore MSC lung adhesion in greater detail. We found a
      striking difference in the lung clearance rate of systemically infused MSCs
      derived from two different clinical sources, namely bone marrow (BM-MSCs) and
      umbilical cord blood (UCB-MSCs). The BM-MSCs and UCB-MSCs used in this study
      differed in cell size, but our results also indicated other mechanisms behind the
      lung adherence. A detailed analysis of the cell surface profiles revealed
      differences in the expression of relevant adhesion molecules. The UCB-MSCs had
      higher expression levels of alpha4 integrin (CD49d, VLA-4), alpha6 integrin
      (CD49f, VLA-6), and the hepatocyte growth factor receptor (c-Met) and a higher
      general fucosylation level. Strikingly, the level of CD49d and CD49f expression
      could be functionally linked with the lung clearance rate. Additionally, we saw a
      possible link between MSC lung adherence and higher fibronectin expression and we
      show that the expression of fibronectin increases with MSC culture confluence.
      Future studies should aim at developing methods of transiently modifying the cell
      surface structures in order to improve the delivery of therapeutic cells.

PMID- 23132821
TI  - The addition of RPMI significantly improves the cellularity of cerebrospinal
      fluid cytology specimens over time.
AB  - BACKGROUND: Cytology specimens of cerebrospinal fluid (CSF) may be hypocellular,
      and the cells in CSF specimens degrade rapidly. METHODS: In the current study,
      the authors attempted to determine whether the addition of RPMI media to CSF
      specimens at the time of their receipt in the laboratory could improve the
      cellularity of specimens that would be processed 24 hours and 48 hours later.
      RESULTS: Compared with the initial specimen that was processed at the time of
      receipt in the laboratory, specimens with RPMI added preserved at least 90% of
      their cellularity. In contrast, specimens that were processed without RPMI lost
      70% and 94% of their cellularity at 24 hours and 48 hours, respectively, even
      with refrigeration. CONCLUSIONS: For CSF specimens that cannot be immediately
      processed, the addition of RPMI appears to significantly improve cellularity at
      24 hours to 48 hours after their receipt in the laboratory.

PMID- 23132823
TI  - Physical activity in a large sample of adults with intellectual disabilities.
AB  - BACKGROUND: Few studies have documented physical activity (PA) and overweight and
      obesity in adults with intellectual disabilities (ID) using both self-report and
      objective methods. We sought to characterize PA in adults with ID and examine the
      associations between self-reported activity types, objectively-measured PA, and
      objectively-measured body mass index (BMI). METHODS: Self-reported PA and BMI
      were measured on 294 adults with ID. Accelerometry was collected on 131 of those
      participants. Differences in BMI and accelerometry by demographic factors and
      activity types were examined. RESULTS: Among the participants, 79.6% were
      overweight or obese and 23.7% met recommended PA guidelines. The mean amount of
      moderate-to-vigorous PA (MVPA) per week was 108.6 minutes. The most common
      activities reported were walking (53.7%) and inside chores (42.5%). Twenty-six
      percent reported no activity. Biking and jogging/running was associated with
      lower BMI. Self reports of playing basketball, softball, and outside chores were
      associated with increased MVPA. CONCLUSION: In this sample of adults with ID,
      most participants were overweight or obese and PA levels were below national
      averages. Select self-reported activities and greater objectively measured PA
      were associated with lower BMI.

PMID- 23132825
TI  - Improvement in structural and functional echocardiographic parameters during
      chronic heart failure therapy guided by natriuretic peptides: mechanistic
      insights from the ProBNP Outpatient Tailored Chronic Heart Failure (PROTECT)
      study.
AB  - AIMS: We sought to determine if heart failure (HF) care with a goal to lower N
      terminal pro B-type natriuretic peptide (NT-proBNP) concentrations, compared with
      standard of care (SOC) management, is associated with improvement in
      echocardiographic parameters of cardiac structure and function. METHODS AND
      RESULTS: Of 151 subjects with HF due to left ventricular systolic dysfunction
      (LVSD) prospectively randomized to NT-proBNP-guided vs. SOC HF care, 116 had
      serial echocardiographic data. Endpoints in this echocardiographic study included
      the relationship between change in NT-proBNP and LV reverse remodelling, as well
      as associations between biomarker-guided therapy and measures of diastolic
      function, right ventricular (RV) size and function, estimates of LV filling
      pressure and RV systolic pressure (RVSP), and the degree of mitral regurgitation
      (MR). After a mean of 10 months of study procedures, in adjusted analyses, final
      NT-proBNP concentrations predicted risk of remodelling [hazard ratio (HR) ?LV end
      diastolic volume index = 1.43, 95% confidence interval (CI) 1.10-1.86, P = 0.007;
      HR ?LV end-systolic volume index = 1.54, 95% CI 1.10-1.91, P = 0.01; HR ?LV
      ejection fraction (LVEF) = 1.53, 905% CI 1.12-1.89, P = 0.02]. In addition to
      greater improvement in LVEF and reductions in LV volume, compared with SOC, NT
      proBNP-guided patients showed significant decreases in the ratio of early
      transmitral peak velocity to early diastolic peak annular velocity (E/E'),
      pulmonary vein peak S velocity, RV fractional area change, RVSP, and MR severity.
      CONCLUSION: NT-proBNP concentrations may serve as a non-invasive indicator of the
      state of cardiac structure and function in HF due to LVSD. Multiple,
      prognostically meaningful echocardiographic variables improved more significantly
      in patients treated with NT-proBNP-guided care vs. SOC.

PMID- 23132824
TI  - Genetic polymorphisms confer risk of atrial fibrillation in patients with heart
      failure: a population-based study.
AB  - AIMS: Atrial fibrillation (AF) is a frequent co-morbidity in heart failure (HF)
      associated with increased mortality, but little is known about the mechanisms
      underlying AF onset in HF patients. We evaluated the association of
      cardiovascular and genetic risk factors with AF in HF patients. METHODS AND
      RESULTS: Individuals hospitalized for HF (n = 1040; 500 with AF) were identified
      from a large, population-based cohort study (n = 30 447; 2339 with AF). Genetic
      polymorphisms in the chromosomal regions 4q25 (rs2200733) and 16q22 (rs2106261)
      associated with AF in genome-wide association studies were genotyped. Association
      of cardiovascular risk factors and polymorphisms with AF was tested in HF
      patients and the entire cohort using both prospective and non-time-dependent
      models. Cardiovascular risk factors-hypertension, body mass index, sex, smoking,
      diabetes, and myocardial infarction-were associated with AF in the entire cohort
      but not in HF patients. In contrast, polymorphisms on chromosomes 16q22 and 4q25
      were associated with AF both in the entire cohort and in HF patients, conferring
      75% [95% confidence interval (CI) 35-126, P = 2 * 10(-5)] and 57% (95% CI 18-109,
      P = 0.002) increased risk of AF per copy in HF patients, respectively. In the
      entire cohort, AF risk in the presence of HF was multiplicatively magnified by
      genotype for 16q22 (P for interaction = 7 * 10(-4)) but not 4q25 (P = 0.83). In
      prospective analyses excluding patients with AF diagnosis prior to or
      simultaneously with HF diagnosis, 16q22 but not 4q25 remained robustly associated
      with AF (hazard ratio 1.96, 95% CI 1.40-2.73, P = 8 * 10(-5)). The proportion of
      AF diagnoses in HF patients attributable to polymorphisms was 19% and 12%,
      respectively. CONCLUSIONS: A polymorphism in the ZFHX3 gene, encoding a cardiac
      transcription factor, was associated with increased AF risk in HF patients, and
      the genetic association with AF was more pronounced in HF patients than in the
      general population.

PMID- 23132826
TI  - Perspectives on asymmetry: the Erickson Lecture.
AB  - Topics discussed include asymmetry of the brain; prosopagnosia with asymmetric
      involvement; the blaspheming brain; effects of the numbers of X chromosomes on
      brain asymmetry; normal facial asymmetry; kissing asymmetry; left- and right
      handedness; left-sided baby cradling; Nodal signaling and left/right asymmetry;
      primary cilium and left/right asymmetry in zebrafish; right/left asymmetry in
      snails; species differences in Shh and Fgf8; primary cilium in vertebrate
      asymmetry; Hedgehog signaling on the cilium; Wnt signaling on the cilium; situs
      solitus, situs inversus, and situs ambiguus (heterotaxy); ciliopathies; right
      sided injuries in trilobites; unilateral ocular use in the octopus; fiddler
      crabs; scale-eating cichlids; narwhals; left-footed parrots; asymmetric whisker
      use in rats; and right-sided fatigue fractures in greyhounds.

PMID- 23132827
TI  - Gata4 blocks somatic cell reprogramming by directly repressing Nanog.
AB  - Somatic cells can be reprogrammed to induced pluripotent stem (iPS) cells by
      ectopic expression of the four factors Oct4, Klf4, Sox2, and Myc. Here, we
      investigated the role of Gata4 in the reprogramming process and present evidence
      for a negative role of this family of transcription factors in the induction of
      pluripotency. Coexpression of Gata4 with Oct4, Klf4, and Sox2 with or without Myc
      in mouse embryonic fibroblasts greatly impaired reprogramming and endogenous
      Nanog expression. The lack of Nanog upregulation was associated with a blockade
      in the transition from the initiation phase of reprogramming to the full
      pluripotent state characteristic of iPS cells. Addition of Nanog to the
      reprogramming cocktail blocked the deleterious effects observed with Gata4
      expression. Downregulation of endogenous Gata4 by short hairpin RNAs during
      reprogramming both accelerated and increased the efficiency of the process and
      augmented the mRNA levels of endogenous Nanog. Using comparative genomics, we
      identified a consensus binding site for Gata factors in an evolutionary conserved
      region located 9 kb upstream of the Nanog gene. Using chromatin
      immunoprecipitation, gel retardation, and luciferase assays, we found that Gata4
      bound to this region and inhibited Nanog transcription in mouse embryonic stem
      cells. Overall, our results describe for first time the negative effect of Gata4
      in the reprogramming of somatic cells and highlight the role of Gata factors in
      the transcriptional networks that control cell lineage choices in the early
      embryo.

PMID- 23132828
TI  - Real-time monitoring of protein conformational dynamics in solution using kinetic
      capillary electrophoresis.
AB  - Conformational analysis: Capillary electrophoresis (CE) allows for the rapid
      separation of slowly interconverting protein conformers. Kinetic analysis
      (k(open), k(closed), and K(d)) of electropherograms in the presence and absence
      of effector ligands allows the measurement of kinetic and thermodynamic constants
      associated with conformational changes and ligand binding.

PMID- 23132829
TI  - Systematic observation of physical activity in afterschool programs: preliminary
      findings from Movin' Afterschool intervention.
AB  - BACKGROUND: National and state organizations have called upon afterschool
      programs (3-6 PM, ASP) to promote physical activity (PA). Few strategies exist
      that ASPs can use to increase the PA of children enrolled. This study evaluated a
      policy-level intervention (Movin' Afterschool, MAS) designed to increase PA
      through staff implemented policy-level changes and ongoing technical support.
      METHODS: Twelve preexisting community-based ASPs serving 580 children (5-12 yrs,
      57% girls) were invited to take part in MAS. Evaluation of children's PA, staff
      behaviors (engaged or promote PA, other ASP tasks, general supervising), and
      environmental features (equipment, organized PA) at baseline (Fall 2010) and
      postassessment (Spring 2011) were collected using SOPLAY (System for Observing
      Play and Leisure Activity in Youth) for boys and girls, separately. Random
      effects models evaluated changes in PA categories (sedentary, walking, vigorous).
      RESULTS: The percentage of boys and girls sedentary decreased by 11.8% and 11.4%,
      respectively. Girls' walking increased by 6.9% while boys' vigorous PA increased
      by 6.5%. Greater increases in vigorous activity were observed as postassessment
      in organized activities for boys and during indoor activities for girls.
      CONCLUSIONS: Findings indicate a policy-level approach targeting staff training
      and ongoing technical support can produce notable increases in PA within the ASP
      setting.

PMID- 23132830
TI  - Word smithing in medical genetics. Part II.
AB  - Terminology discussed here is subsumed under "common misused terms in medical
      genetics articles" (depressed nasal bridge; anophthalmia; rotated ears; low-set
      ears; heterotopia; ASD as an abbreviation for autism spectrum disorders; mental
      retardation; "radiographs revealed something"; and new syndrome) and also
      subsumed under "erroneous terminology that persists at the editorial and
      publishing level" (failure to understand the possessive case of names ending in
      "s"; failure to understand that a comma should not be used before Jr; problematic
      use of numbers in reference sections; failure to italicize Latin phrases; failure
      to honor book titles that begin words with upper case letters; omitting the
      corresponding author; and inadequate citation of foreign languages).

PMID- 23132833
TI  - Solar-driven incorporation of carbon dioxide into alpha-amino ketones.

PMID- 23132832
TI  - Permanent deficits in handgrip strength and running speed performance in low
      birth weight children.
AB  - OBJECTIVE: The main goal of this study was to verify the influence of low birth
      weight (LBW) on the physical fitness of children aged 7-10 years. The comparisons
      were subsequently adjusted for chronological age, gender, physical activity (PA),
      and body composition. METHODS: A total of 356 children of both genders born in
      Vitoria de Santo Antao (Northeast of Brazil) were divided into two groups
      according to their birth weight (LBW < 2.500 g, n = 100, and normal birth weight,
      NBW >= 3.000 g and <= 3.999 g, n = 256). Body composition measurements included
      body weight, height, body mass index, triceps, and subscapular skinfolds, and
      body fat percentage (%BF). PA was assessed by a questionnaire. Physical fitness
      was assessed by handgrip strength, muscle endurance, explosive power,
      flexibility, agility, maximal oxygen consumption (VO(2max) ), and running speed.
      RESULTS: LBW children were shorter, lighter, had lower fat-free mass, muscle
      strength, and running speed but a higher VO(2max) than the NBW group. The
      differences in body weight (P = 0.507), height (P = 0.177), fat-free mass (P =
      0.374), and VO(2max) (P = 0.312) disappeared when adjusted for covariates. The
      differences in right and left handgrip strength (P < 0.01) and running speed (P <
      0.01) remained significant even when controlled for age, gender, height, fat-free
      mass, and PA. CONCLUSION: This combined analysis suggests that LBW alone can be
      not considered as a biological determinant of growth, body composition, or
      physical fitness in children, but is a predictor of muscle strength and running
      speed.

PMID- 23132834
TI  - Use of the Pregnancy Physical Activity Questionnaire (PPAQ) to identify
      behaviours associated with appropriate gestational weight gain during pregnancy.
AB  - BACKGROUND: The Pregnancy Physical Activity Questionnaire (PPAQ) assesses
      physical activity practices of pregnant women. The purpose of this study was to
      identify specific pregnancy practices that were associated with a healthy
      gestational weight gain (GWG). METHODS: Associations between PPAQ scores,
      pedometer steps, energy intakes (EI), energy expenditures (EE), and rate of GWG
      were assessed for 61 pregnant women in their second or third trimester during a
      home visit. Principle component analyses (PCA) were used to cluster PPAQ
      questions into FACTORS associated with either rate or total GWG, physical
      activity (PA), EE, EI, and parity. RESULTS: PCA identified 3 FACTORS: Factor 1
      associated EE with parity and child care; Factor 2 clustered several structured
      exercise activities; and Factor 3 grouped walking, playing with pets, and
      shopping with pedometer steps. Only Factor 3 clustered steps with weekly rate of
      GWG. EI was not associated with PA or GWG. CONCLUSIONS: PCA analysis identified
      15 of 32 PPAQ questions that were related to increased physical activity in
      pregnant women, but only walking and pedometer steps were associated with GWG.
      Our analysis supports daily walking as the preferred PA for achieving a healthy
      rate of GWG.

PMID- 23132831
TI  - Effective elimination of cancer stem cells by a novel drug combination strategy.
AB  - Development of effective therapeutic strategies to eliminate cancer stem cells,
      which play a major role in drug resistance and disease recurrence, is critical to
      improve cancer treatment outcomes. Our study showed that glioblastoma stem cells
      (GSCs) exhibited low mitochondrial respiration and high glycolytic activity.
      These GSCs were highly resistant to standard drugs such as carmustine and
      temozolomide (TMZ), but showed high sensitivity to a glycolytic inhibitor 3-bromo
      2-oxopropionate-1-propyl ester (3-BrOP), especially under hypoxic conditions. We
      further showed that combination of 3-BrOP with carmustine but not with TMZ
      achieved a striking synergistic effect and effectively killed GSCs through a
      rapid depletion of cellular ATP and inhibition of carmustine-induced DNA repair.
      This drug combination significantly impaired the sphere-forming ability of GSCs
      in vitro and tumor formation in vivo, leading to increase in the overall survival
      of mice bearing orthotopic inoculation of GSCs. Further mechanistic study showed
      that 3-BrOP and carmustine inhibited glyceraldehyde-3-phosphate dehydrogenase and
      caused a severe energy crisis in GSCs. Our study suggests that GSCs are highly
      glycolytic and that certain drug combination strategies can be used to
      effectively overcome their drug resistance based on their metabolic properties.

PMID- 23132835
TI  - Plasma B vitamins and LINE-1 DNA methylation in leukocytes of patients with a
      history of colorectal adenomas.
AB  - SCOPE: Low concentrations of folate, other B vitamins, and methionine are
      associated with colorectal cancer risk, possibly by changing DNA methylation
      patterns. Here, we examine whether plasma concentrations of B vitamins and
      methionine are associated with methylation of long interspersed nuclear element-1
      (LINE-1) among those at high risk of colorectal cancer, i.e. patients with at
      least one histologically confirmed colorectal adenoma (CRA) in their life.
      METHODS AND RESULTS: We used LINE-1 bisulfite pyrosequencing to measure global
      DNA methylation levels in leukocytes of 281 CRA patients. Multivariable linear
      regression was used to assess associations between plasma B vitamin
      concentrations and LINE-1 methylation levels. Plasma folate was inversely
      associated with LINE-1 methylation in CRA patients, while plasma methionine was
      positively associated with LINE-1 methylation. CONCLUSION: This study does not
      provide evidence that in CRA patients, plasma folate concentrations are
      positively related to LINE-1 methylation in leukocytes but does suggest a direct
      association between plasma methionine and LINE-1 methylation in leukocytes.

PMID- 23132837
TI  - Synthesis of aromatic nitriles using nonmetallic cyano-group sources.
AB  - Aromatic nitriles are prepared efficiently through transition-metal-mediated
      cyanation of aryl (pseudo)halides with metallic cyano-group sources, such as
      CuCN, KCN, NaCN, Zn(CN)(2), TMSCN, or K(4) [Fe(CN)(6)]. However, this approach
      often suffers from drawbacks, such as the formation of stoichiometric amounts of
      metal waste, the poisoning of the metal catalysts, or the generation of toxic HCN
      gas. As a result, a range of "nonmetallic" organic cyano-group sources have been
      explored for the cyanation of aryl halides and arene C-H bonds. This Minireview
      summarizes types of nonmetallic cyano-group sources and their applications in the
      preparation of aryl nitriles.

PMID- 23132836
TI  - Epigenetic regulation of survivin by Bmi1 is cell type specific during
      corticogenesis and in gliomas.
AB  - Polycomb group proteins are essential regulators of stem cell function during
      embryonic development and in adult tissue homeostasis. Bmi1, a key component of
      the Polycomb Repressive Complex 1, is highly expressed in undifferentiated neural
      stem cells (NSC) as well as in several human cancers including high-grade gliomas
      -highly aggressive brain tumors. Using a conditional gene activation approach in
      mice, we show that overexpression of Bmi1 induces repressive epigenetic
      regulation of the promoter of Survivin, a well-characterized antiapoptotic
      protein. This phenomenon is cell type-specific and it leads to apoptotic death of
      progenitor cells exclusively upon commitment toward a neuronal fate. Moreover, we
      show that this is triggered by increased oxidative stress-induced DNA damage. In
      contrast, undifferentiated NSC as well as glioma-initiating cells display an open
      chromatin configuration at the Survivin promoter and do not undergo apoptotic
      death. These findings raise the possibility that normal and neoplastic stem cells
      depend on the same mechanism for surviving the hyperproliferative state induced
      by increased Bmi1 expression.

PMID- 23132839
TI  - Writing well: a writing style checklist to promote publication among
      practitioners.

PMID- 23132838
TI  - Developing a computer touch-screen interactive colorectal screening decision aid
      for a low-literacy African American population: lessons learned.
AB  - African Americans have higher colorectal cancer (CRC) mortality than White
      Americans and yet have lower rates of CRC screening. Increased screening aids in
      early detection and higher survival rates. Coupled with low literacy rates, the
      burden of CRC morbidity and mortality is exacerbated in this population, making
      it important to develop culturally and literacy appropriate aids to help low
      literacy African Americans make informed decisions about CRC screening. This
      article outlines the development of a low-literacy computer touch-screen
      colonoscopy decision aid using an innovative marketing method called perceptual
      mapping and message vector modeling. This method was used to mathematically model
      key messages for the decision aid, which were then used to modify an existing CRC
      screening tutorial with different messages. The final tutorial was delivered
      through computer touch-screen technology to increase access and ease of use for
      participants. Testing showed users were not only more comfortable with the touch
      screen technology but were also significantly more willing to have a colonoscopy
      compared with a "usual care group." Results confirm the importance of including
      participants in planning and that the use of these innovative mapping and message
      design methods can lead to significant CRC screening attitude change.

PMID- 23132840
TI  - Intergenerational photovoice projects: optimizing this mechanism for influencing
      health promotion policies and strengthening relationships.
AB  - Intergenerational photovoice groups are promising for promoting health through
      the topic that is explored and through group dynamics that can foster healthy
      relationships and communication. To investigate the potential benefits of
      intergenerational photovoice projects, photovoice groups were conducted in urban
      Minnesota, United States, and in rural Morelos, Mexico, between 2009 and 2012
      with Mexican-origin adults and their adolescent relatives. Seven photovoice
      groups of adult-adolescent dyads met for eight sessions and developed exhibits
      highlighting their views on health and migration and made policy recommendations,
      using messages conveyed through their words and photographs. Informal process
      evaluation and focus groups were used to elicit feedback about photovoice project
      participation. Photovoice project themes were descriptively analyzed. Focus group
      evaluation data were thematically summarized, and facilitator reflections were
      descriptively summarized to identify factors associated with intergenerational
      photovoice groups. Seventy-five participants were recruited. Photovoice themes
      represented effects of migration on health, family, and well-being. The following
      two evaluative themes were identified: (a) participant sentiments about the
      benefits of photovoice participation and (b) facilitator observations of
      intergenerational photovoice group benefits and challenges. Participants
      described opportunities to learn new things and barriers to healthy relationships
      that the project was eliminating by providing them with time to work together.
      Used in health promotion, photovoice is a valuable tool that contributes to
      understanding the complex underlying factors influencing behaviors and health. 

PMID- 23132841
TI  - A model for evaluating the activities of a coalition-based policy action group:
      the case of Hermosa Vida.
AB  - Scholars and clinicians are increasingly recognizing the complexity of social
      contexts of health and the need for multifunctioning approaches to health care
      problems including community- and policy-level strategies. Barriers to change in
      health care policy can sometimes be attributed to the actions of advocacy
      coalitions who operate from a limited view of "policy change." Advocates have a
      tendency to pressure stakeholders to mandate laws as a final resolution of a
      movement, often leading to failure or, worse, stigmatizing of issues. A more
      inclusive focus on health policy change as an ongoing process increases the
      efficacy of advocacy and outcomes measurement. This article presents a tool for
      policy action that coalition members developed through the implementation of a 3
      year grant to improve the safety net for preventing childhood obesity. Scholars
      and policy makers developed the Policy Coalition Evaluation Tool with the intent
      to create a model to guide and measure efforts and outcomes of a local community
      based policy coalition. The authors suggest using community-based participatory
      research approaches for developing a coalition-specific Policy Coalition
      Evaluation Tool to increase the effectiveness of advocacy groups and the
      documentation of coalition activities over time.

PMID- 23132842
TI  - An examination of multilevel factors that may explain gender differences in
      children's physical activity.
AB  - BACKGROUND: Girls are less physically active than boys, yet no single study has
      examined the factors that may explain gender differences in children's physical
      activity (PA). METHODS: This study was a cross-sectional analysis of data from
      116 caregivers and their children aged 5-8 years who participated in the MOVE
      study. Caregivers reported various factors that may relate to children's PA (eg,
      encouragement for child PA and PA equipment at home). Child PA was measured by 7
      day accelerometry. Linear regression tested for the variance in moderate-to
      vigorous physical activity (MVPA) explained by gender and several variables.
      Gender and ethnicity interactions were examined. RESULTS: Caregivers were mostly
      female (97%), mean age 38 +/- 6 years, mean BMI 28 +/- 6 (kg/m2). Child's mean
      age was 8.1 +/- 0.7, 54% were female and 40% were overweight/obese. Girls were
      less physically active than boys (54.1 +/- 19.7 vs. 65.2 +/- 28.0 daily minutes
      of MVPA, respectively). Among girls, more days of PE/week was associated with
      greater MVPA. Among boys, greater parent support for PA, greater parent modeling
      for PA, and greater number of PA equipment in the home were associated with
      greater MVPA. CONCLUSIONS: This study supports that boys and girls have different
      correlates for MVPA, which may partly explain gender differences in PA.

PMID- 23132843
TI  - Synthesis and evaluation of 3,4-dihydropyrimidin-2(1H)-ones as sodium iodide
      symporter inhibitors.
AB  - The sodium iodide symporter (NIS) is responsible for the accumulation of iodide
      in the thyroid gland. This transport process is involved in numerous thyroid
      dysfunctions and is the basis for human contamination in the case of exposure to
      radioactive iodine species. 4-Aryl-3,4-dihydropyrimidin-2(1H)-ones were recently
      discovered by high-throughput screening as the first NIS inhibitors. Described
      herein are the synthesis and evaluation of 115 derivatives with structural
      modifications at five key positions on the pyrimidone core. This study provides
      extensive structure-activity relationships for this new class of inhibitors that
      will serve as a basis for further development of compounds with in vivo efficacy
      and adequate pharmacokinetic properties. In addition, the SAR investigation
      provided a more potent compound, which exhibits an IC(50)  value of 3.2 nM in a
      rat thyroid cell line (FRTL5).

PMID- 23132844
TI  - Examining the associations of perceived community racism with self-reported
      physical activity levels and health among older racial minority adults.
AB  - BACKGROUND: Racial health disparities are more pronounced among older adults. Few
      studies have examined how racism influences health behaviors. This study's
      purpose was to examine how opportunities for physical activity (PA) and community
      racism are associated with older racial minorities' reported engagement in PA. We
      also investigated how PA levels influenced health. METHODS: We analyzed survey
      data obtained from a health assessment conducted in 3360 households in Texas,
      USA, which included items pertaining to PA, community characteristics, and
      health. RESULTS: Our sample contained 195 women and 85 men (mean age 70.16), most
      of whom were African American. We found no direct relationship between
      opportunities and PA. Results suggested that perceived community racism moderated
      this association. When community racism was low, respondents found ways to be
      active whether they perceived opportunities or not. When community racism was
      high, perceived lack of opportunities significantly impeded PA engagement. We
      found the expected association between PA and health. CONCLUSIONS: Results
      suggested that negative effects of community racism were counteracted through
      increased opportunities for PA.

PMID- 23132845
TI  - Reflections on my journey in biomedical research: the art, science, and politics
      of advocacy.
AB  - Scientific Discovery often reflects the art, science, and advocacy for biomedical
      research. Here the author reflects on selected highlights of discovery that
      contributed to several aspects of our understanding of craniofacial biology and
      craniofacial diseases and disorders.

PMID- 23132847
TI  - Chemotherapy and radiation regimens to breast cancer treatment induce changes in
      mRNA levels of renin-angiotensin system related genes in cardiac tissue.
AB  - BACKGROUND AND AIM: Cardiovascular complications are one limitation of breast
      cancer treatment. The aim of the current study was to investigate whether the
      renin-angiotensin related genes could be altered by chemotherapy and
      radiotherapy, using a rat model. METHODS: Female rats were divided into three
      groups: control, chemotherapy + irradiation (TC+IR) and irradiation (IR).
      Molecular analyses of the left ventricle were performed five months after the end
      of treatment. The analyses evaluated the changes in mRNA levels of some renin
      angiotensin system (RAS) related genes: angiotensinogen, renin, angiotensin
      converting enzyme (ACE) and angiotensin II type 1 receptor (AT1) and vascular
      endothelial growth factor (VEGF), which can be related to ACE production, by RT
      PCR. RESULTS: Renin was only observed in treated groups, TC+IR and IR, compared
      with the control group. ACE and VEGF levels were decreased in TC+IR (p<0.001) and
      in IR (p<0.001), and AT1 mRNA was higher in groups TC+IR (p<0.01) and IR (p<0.05)
      compared with the control group. CONCLUSION: Chemotherapy and irradiation can
      induce significant changes in some RAS related genes. These alterations are
      important to understand the pathways and consequences beyond cardiotoxicity
      induced by breast cancer treatments.

PMID- 23132846
TI  - Local hematopoietic renin-angiotensin system in myeloid versus lymphoid
      hematological neoplastic disorders.
AB  - There is preliminary evidence that the local renin-angiotensin system (RAS) could
      affect neoplastic hematopoiesis. The aim of this study is to search messenger RNA
      (mRNA) expressions of the essential RAS elements in myeloid and lymphoid
      hematological neoplastic disorders. Forty-six patients with newly diagnosed
      myeloid (AML, biphenotypic leukemia, CML) or lymphoid (CLL, NHL, B-ALL, T-ALL)
      hematological disorders were included in the study. In the lymphoid group, the
      median expression values of RENIN, ACE1, ACE2 and ANGIOTENSINOGEN (ANGTS) mRNAs
      were 1.96%, 0.42%, 0.00% and 0.00%, respectively; in the myeloid group, 0.73%,
      1.55%, 0.04% and 0.006%, respectively. In the lymphoid group, RENIN levels were
      significantly higher (p = 0.001), whereas ACE1 and ACE2 levels were significantly
      higher in the myeloid group (p values were 0.013 and 0.010, respectively). ANGTS
      levels were similar in both groups. In patients with non-ALL lymphoid
      malignancies, RENIN expressions were significantly higher when compared to ALL
      patients (p = 0.004). All patients with active disease had significantly higher
      RENIN mRNA expression levels than patients without active disease (2.03% vs
      0.30%) (p = 0.034). The result of our present study indicates that the activities
      of local RAS may differ in distinct disease states such as leukemia and
      lymphomas. 

PMID- 23132848
TI  - Efficacy of aliskiren and valsartan in hypertensive patients with albuminuria: a
      randomized parallel-group study.
AB  - INTRODUCTION: Blockade of the renin-angiotensin system (RAS) is a critical
      approach to the management of hypertension, especially in proteinuric patients.
      It is well proven that the direct renin inhibitor aliskiren shows comparable
      clinical efficacy to the angiotensin II receptor blocker valsartan on blood
      pressure control and albuminuria. However, there is only limited data on the hand
      to-hand effectiveness of these two RAS blockers in improving arterial stiffness.
      We tested whether aliskiren or valsartan would improve arterial stiffness in
      hypertensive patients with albuminuria who are already on antihypertensive
      therapy. MATERIAL AND METHODS: Thirty-four patients with hypertension and
      albuminuria < 1 g, after a wash-out period of three weeks, were randomized to
      aliskiren or valsartan in a 24-week randomized parallel-group study. RESULTS: A
      nonsignificant difference in blood pressure was seen between the two treatment
      groups. Albuminuria was significantly reduced in both groups (56% for the
      aliskiren group, p < 0.05, and 38% for the valsartan group, p < 0.05). Only
      valsartan but not aliskiren significantly reduced carotid-femoral pulse wave
      velocity (-1.1 +/- 0.8 m/s (p = 0.02) for valsartan and +0.1 +/- 0.7 m/s (ns) for
      aliskiren). CONCLUSION: The results of our study showed that valsartan improves
      arterial stiffness to a significantly greater extent than aliskiren, despite a
      similar antihypertensive and antiproteinuric effect.

PMID- 23132849
TI  - Attention to fidelity: why is it important.

PMID- 23132850
TI  - Comment on Editorial Literature Reviews as a Research Strategy.

PMID- 23132852
TI  - Foamy virus envelope protein is a substrate for signal peptide peptidase-like 3
      (SPPL3).
AB  - Signal peptide peptidase (SPP), its homologs, the SPP-like proteases SPPL2a/b/c
      and SPPL3, as well as presenilin, the catalytic subunit of the gamma-secretase
      complex, are intramembrane-cleaving aspartyl proteases of the GxGD type. In this
      study, we identified the 18-kDa leader peptide (LP18) of the foamy virus envelope
      protein (FVenv) as a new substrate for intramembrane proteolysis by human SPPL3
      and SPPL2a/b. In contrast to SPPL2a/b and gamma-secretase, which require
      substrates with an ectodomain shorter than 60 amino acids for efficient
      intramembrane proteolysis, SPPL3 cleaves mutant FVenv lacking the proprotein
      convertase cleavage site necessary for the prior shedding. Moreover, the cleavage
      product of FVenv generated by SPPL3 serves as a new substrate for consecutive
      intramembrane cleavage by SPPL2a/b. Thus, human SPPL3 is the first GxGD-type
      aspartyl protease shown to be capable of acting like a sheddase, similar to
      members of the rhomboid family, which belong to the class of intramembrane
      cleaving serine proteases.

PMID- 23132853
TI  - Activation of the SNF2 family ATPase ALC1 by poly(ADP-ribose) in a stable
      ALC1.PARP1.nucleosome intermediate.
AB  - The human ALC1/CHD1L oncogene encodes an SNF2 family ATPase with a macrodomain
      that binds poly(ADP-ribose) (PAR). We and others previously showed that ALC1
      possesses a cryptic ATP-dependent nucleosome remodeling activity that is potently
      activated in the presence of PARP1 and NAD(+), its substrate for PAR synthesis.
      In this work, we dissected the mechanism by which PARP1 and NAD(+) activate ALC1
      nucleosome remodeling. We demonstrate that ALC1 activation depends on the
      formation of a stable ALC1.PARylated PARP1.nucleosome intermediate. In addition,
      by exploiting a novel PAR footprinting assay, we obtained evidence that the ALC1
      macrodomain remains stably associated with PAR on autoPARylated PARP1 during the
      course of nucleosome remodeling reactions. Taken together, our findings are
      consistent with the model that PAR present on PARylated PARP1 acts as an
      allosteric effector of ALC1 nucleosome remodeling activity.

PMID- 23132854
TI  - Binding of the N-terminal region of coactivator TIF2 to the intrinsically
      disordered AF1 domain of the glucocorticoid receptor is accompanied by
      conformational reorganizations.
AB  - Control of gene transcription by glucocorticoid receptors (GRs) is important for
      many physiological processes. Like other steroid hormone receptors, the
      regulation of target genes by GR is mediated by two transactivation domains:
      activation function 1 (AF1) in the N-terminal domain and AF2 in the C-terminal
      ligand-binding domain (LBD). Full receptor activity requires both AF1 and -2 plus
      assorted coregulatory proteins. Crystal structures of the ligand-bound LBD have
      provided insight regarding how AF2 interacts with specific coactivators. However,
      despite its being the major activation domain of GRs, knowledge of AF1
      structure/function has languished. This is mainly because of the highly
      disorganized structure of the GR N-terminal domain. This lack of AF1 structure is
      shared by all members of the steroid/nuclear receptor superfamily for which it
      has been examined and AF1 is thought to allow productive interactions with
      assorted cofactors via protein-induced changes in secondary/tertiary structures.
      To date, there are no reports of a classical coactivator altering the
      secondary/tertiary structure of the GR AF1 domain. Earlier, we reported an N
      terminal fragment of the p160 coactivator TIF2, called TIF2.0, that binds the GR
      N-terminal domain and alters GR transcriptional activity. We therefore proposed
      that TIF2.0 binding to AF1 changes both its conformation and transcriptional
      activity. We now report that TIF2.0 interacts with the GR AF1 domain to increase
      the amount of alpha-helical structure in the complex. Furthermore, TIF2
      coactivator activity is observed in the absence of the GR LBD in a manner that
      requires the AF1 domain. This contrasts with previous models where TIF2 receptor
      interaction domains binding to GR LBD somehow alter AF1 conformation. Our results
      establish for the first time that coactivators can modify the structure of the
      AF1 domain directly via the binding of a second region of the coactivator and
      suggest a molecular explanation for how coactivators increase the transcriptional
      activity of GR-agonist complexes.

PMID- 23132855
TI  - Kinin-B2 receptor activity determines the differentiation fate of neural stem
      cells.
AB  - Bradykinin is not only important for inflammation and blood pressure regulation,
      but also involved in neuromodulation and neuroprotection. Here we describe novel
      functions for bradykinin and the kinin-B2 receptor (B2BkR) in differentiation of
      neural stem cells. In the presence of the B2BkR antagonist HOE-140 during rat
      neurosphere differentiation, neuron-specific beta3-tubulin and enolase expression
      was reduced together with an increase in glial protein expression, indicating
      that bradykinin-induced receptor activity contributes to neurogenesis. In
      agreement, HOE-140 affected in the same way expression levels of neural markers
      during neural differentiation of murine P19 and human iPS cells. Kinin-B1
      receptor agonists and antagonists did not affect expression levels of neural
      markers, suggesting that bradykinin-mediated effects are exclusively mediated via
      B2BkR. Neurogenesis was augmented by bradykinin in the middle and late stages of
      the differentiation process. Chronic treatment with HOE-140 diminished eNOS and
      nNOS as well as M1-M4 muscarinic receptor expression and also affected purinergic
      receptor expression and activity. Neurogenesis, gliogenesis, and neural migration
      were altered during differentiation of neurospheres isolated from B2BkR knock-out
      mice. Whole mount in situ hybridization revealed the presence of B2BkR mRNA
      throughout the nervous system in mouse embryos, and less beta3-tubulin and more
      glial proteins were expressed in developing and adult B2BkR knock-out mice
      brains. As a underlying transcriptional mechanism for neural fate determination,
      HOE-140 induced up-regulation of Notch1 and Stat3 gene expression. Because
      pharmacological treatments did not affect cell viability and proliferation, we
      conclude that bradykinin-induced signaling provides a switch for neural fate
      determination and specification of neurotransmitter receptor expression.

PMID- 23132856
TI  - Structural enzymology of Cellvibrio japonicus Agd31B protein reveals alpha
      transglucosylase activity in glycoside hydrolase family 31.
AB  - The metabolism of the storage polysaccharides glycogen and starch is of vital
      importance to organisms from all domains of life. In bacteria, utilization of
      these alpha-glucans requires the concerted action of a variety of enzymes,
      including glycoside hydrolases, glycoside phosphorylases, and transglycosylases.
      In particular, transglycosylases from glycoside hydrolase family 13 (GH13) and
      GH77 play well established roles in alpha-glucan side chain (de)branching,
      regulation of oligo- and polysaccharide chain length, and formation of cyclic
      dextrans. Here, we present the biochemical and tertiary structural
      characterization of a new type of bacterial 1,4-alpha-glucan 4-alpha
      glucosyltransferase from GH31. Distinct from 1,4-alpha-glucan 6-alpha
      glucosyltransferases (EC 2.4.1.24) and 4-alpha-glucanotransferases (EC 2.4.1.25),
      this enzyme strictly transferred one glucosyl residue from alpha(1->4)-glucans in
      disproportionation reactions. Substrate hydrolysis was undetectable for a series
      of malto-oligosaccharides except maltose for which transglycosylation nonetheless
      dominated across a range of substrate concentrations. Crystallographic analysis
      of the enzyme in free, acarbose-complexed, and trapped 5-fluoro-beta-glucosyl
      enzyme intermediate forms revealed extended substrate interactions across one
      negative and up to three positive subsites, thus providing structural
      rationalization for the unique, single monosaccharide transferase activity of the
      enzyme.

PMID- 23132857
TI  - Multiple NF-kappaB sites in HIV-1 subtype C long terminal repeat confer superior
      magnitude of transcription and thereby the enhanced viral predominance.
AB  - We demonstrate that at least three different promoter variant strains of HIV-1
      subtype C have been gradually expanding and replacing the standard subtype C
      viruses in India, and possibly in South Africa and other global regions, over the
      past decade. The new viral strains contain an additional NF-kappaB, NF-kappaB
      like, or RBEIII site in the viral promoter. Although the acquisition of an
      additional RBEIII site is a property shared by all the HIV-1 subtypes, acquiring
      an additional NF-kappaB site remains an exclusive property of subtype C. The
      acquired kappaB site is genetically distinct, binds the p50-p65 heterodimer, and
      strengthens the viral promoter at the levels of transcription initiation and
      elongation. The 4-kappaB viruses dominate the 3-kappaB "isogenic" viral strains
      in pairwise competition assays in T-cell lines, primary cells, and the ecotropic
      human immunodeficiency virus mouse model. The dominance of the 4-kappaB viral
      strains is also evident in the natural context when the subjects are coinfected
      with kappaB-variant viral strains. The mean plasma viral loads, but not CD4
      counts, are significantly different in 4-kappaB infection suggesting that these
      newly emerging strains are probably more infectious. It is possible that higher
      plasma viral loads underlie selective transmission of the 4-kappaB viral strains.
      Several publications previously reported duplication or deletion of diverse
      transcription factor-binding sites in the viral promoter. Unlike previous
      reports, our study provides experimental evidence that the new viral strains
      gained a potential selective advantage as a consequence of the acquired
      transcription factor-binding sites and importantly that these strains have been
      expanding at the population level.

PMID- 23132858
TI  - Differential regulation of amyloid-beta endocytic trafficking and lysosomal
      degradation by apolipoprotein E isoforms.
AB  - Aggregation of amyloid-beta (Abeta) peptides leads to synaptic disruption and
      neurodegeneration in Alzheimer disease (AD). A major Abeta clearance pathway in
      the brain is cellular uptake and degradation. However, how Abeta traffics through
      the endocytic pathway and how AD risk factors regulate this event is unclear.
      Here we show that the majority of endocytosed Abeta in neurons traffics through
      early and late endosomes to the lysosomes for degradation. Overexpression of Rab5
      or Rab7, small GTPases that function in vesicle fusion for early and late
      endosomes, respectively, significantly accelerates Abeta endocytic trafficking to
      the lysosomes. We also found that a portion of endocytosed Abeta traffics through
      Rab11-positive recycling vesicles. A blockage of this Abeta recycling pathway
      with a constitutively active Rab11 mutant significantly accelerates cellular
      Abeta accumulation. Inhibition of lysosomal enzymes results in Abeta accumulation
      and aggregation. Importantly, apolipoprotein E (apoE) accelerates neuronal Abeta
      uptake, lysosomal trafficking, and degradation in an isoform-dependent manner
      with apoE3 more efficiently facilitating Abeta trafficking and degradation than
      apoE4, a risk factor for AD. Taken together, our results demonstrate that Abeta
      endocytic trafficking to lysosomes for degradation is a major Abeta clearance
      pathway that is differentially regulated by apoE isoforms. A disturbance of this
      pathway can lead to accumulation and aggregation of cellular Abeta capable of
      causing neurotoxicity and seeding amyloid.

PMID- 23132859
TI  - Novel alpha2beta1 integrin inhibitors reveal that integrin binding to collagen
      under shear stress conditions does not require receptor preactivation.
AB  - The interaction between alpha2beta1 integrin (GPIa/IIa, VLA-2) and vascular
      collagen is one of the initiating events in thrombus formation. Here, we describe
      two structurally similar sulfonamide derivatives, BTT-3033 and BTT-3034, and show
      that, under static conditions, they have an almost identical effect on alpha2
      expressing CHO cell adhesion to collagen I, but only BTT-3033 blocks platelet
      attachment under flow (90 dynes/cm(2)). Differential scanning fluorimetry showed
      that both molecules bind to the alpha2I domain of the recombinant alpha2 subunit.
      To further study integrin binding mechanism(s) of the two sulfonamides, we
      created an alpha2 Y285F mutant containing a substitution near the metal ion
      dependent adhesion site motif in the alpha2I domain. The action of BTT-3033,
      unlike that of BTT-3034, was dependent on Tyr-285. In static conditions BTT-3034,
      but not BTT-3033, inhibited collagen binding by an alpha2 variant carrying a
      conformationally activating E318W mutation. Conversely, in under flow conditions
      (90 dynes/cm(2)) BTT-3033, but not BTT-3034, inhibited collagen binding by an
      alpha2 variant expressing E336A loss-of-function mutation. Thus, the binding
      sites for BTT-3033 and BTT-3034 are differentially available in distinct integrin
      conformations. Therefore, these sulfonamides can be used to study the biological
      role of different functional stages of alpha2beta1. Furthermore, only the
      inhibitor that recognized the non-activated conformation of alpha2beta1 integrin
      under shear stress conditions effectively blocked platelet adhesion, suggesting
      that the initial interaction between integrin and collagen takes place prior to
      receptor activation.

PMID- 23132860
TI  - Structural and functional characterization of the kindlin-1 pleckstrin homology
      domain.
AB  - Inside-out activation of integrins is mediated via the binding of talin and
      kindlin to integrin beta-subunit cytoplasmic tails. The kindlin FERM domain is
      interrupted by a pleckstrin homology (PH) domain within its F2 subdomain. Here,
      we present data confirming the importance of the kindlin-1 PH domain for integrin
      activation and its x-ray crystal structure at a resolution of 2.1 A revealing a C
      terminal second alpha-helix integral to the domain but found only in the kindlin
      protein family. An isoform-specific salt bridge occludes the canonical
      phosphoinositide binding site, but molecular dynamics simulations display
      transient switching to an alternative open conformer. Molecular docking reveals
      that the opening of the pocket would enable potential ligands to bind within it.
      Although lipid overlay assays suggested the PH domain binds inositol
      monophosphates, surface plasmon resonance demonstrated weak affinities for
      inositol 3,4,5-triphosphate (Ins(3,4,5)P(3); K(D) ~100 MUM) and no monophosphate
      binding. Removing the salt bridge by site-directed mutagenesis increases the PH
      domain affinity for Ins(3,4,5)P(3) as measured by surface plasmon resonance and
      enables it to bind PtdIns(3,5)P(2) on a dot-blot. Structural comparison with
      other PH domains suggests that the phosphate binding pocket in the kindlin-1 PH
      domain is more occluded than in kindlins-2 and -3 due to its salt bridge. In
      addition, the apparent affinity for Ins(3,4,5)P(3) is affected by the presence of
      PO(4) ions in the buffer. We suggest the physiological ligand of the kindlin-1 PH
      domain is most likely not an inositol phosphate but another phosphorylated
      species.

PMID- 23132861
TI  - ngs (notochord granular surface) gene encodes a novel type of intermediate
      filament family protein essential for notochord maintenance in zebrafish.
AB  - The notochord is an important organ involved in embryonic patterning and
      locomotion. In zebrafish, the mature notochord consists of a single stack of
      fully differentiated, large vacuolated cells called chordocytes, surrounded by a
      single layer of less differentiated notochordal epithelial cells called
      chordoblasts. Through genetic analysis of zebrafish lines carrying pseudo-typed
      retroviral insertions, a mutant exhibiting a defective notochord with a granular
      appearance was isolated, and the corresponding gene was identified as ngs
      (notochord granular surface), which was specifically expressed in the notochord.
      In the mutants, the notochord started to degenerate from 32 hours post
      fertilization, and the chordocytes were then gradually replaced by smaller cells
      derived from chordoblasts. The granular notochord phenotype was alleviated by
      anesthetizing the mutant embryos with tricaine to prevent muscle contraction and
      locomotion. Phylogenetic analysis showed that ngs encodes a new type of
      intermediate filament (IF) family protein, which we named chordostatin based on
      its function. Under the transmission electron microcopy, bundles of 10-nm-thick
      IF-like filaments were enriched in the chordocytes of wild-type zebrafish
      embryos, whereas the chordocytes in ngs mutants lacked IF-like structures.
      Furthermore, chordostatin-enhanced GFP (EGFP) fusion protein assembled into a
      filamentous network specifically in chordocytes. Taken together, our work
      demonstrates that ngs encodes a novel type of IF protein and functions to
      maintain notochord integrity for larval development and locomotion. Our work
      sheds light on the mechanisms of notochord structural maintenance, as well as the
      evolution and biological function of IF family proteins.

PMID- 23132862
TI  - The NC2 domain of type IX collagen determines the chain register of the triple
      helix.
AB  - Precise mapping and unraveling the mechanism of interaction or degradation of a
      certain type of collagen triple helix requires the generation of short and stable
      collagenous fragments. This is a great challenge especially for hetero-trimeric
      collagens, where chain composition and register (stagger) are important factors.
      No system has been reported that can be efficiently used to generate a natural
      collagenous fragment with exact chain composition and desired chain register. The
      NC2 domain (only 35-50 residues) of FACIT collagens is a potent trimerization
      domain. In the case of type IX collagen it provides the efficient selection and
      hetero-trimerization of three distinct chains. The ability of the NC2 domain to
      determine the chain register of the triple helix is studied. We generated three
      possible sequence combinations (alpha1alpha1alpha2, alpha1alpha2alpha1,
      alpha2alpha1alpha1) of a type I collagen fragment (the binding region for the von
      Willebrand factor A3 domain) attached to the NC2 domain. In addition, two control
      combinations were produced that constitute homo-trimers of (alpha1)(3) or
      (alpha2)(3). For the hetero-trimeric constructs, alpha1alpha1alpha2 demonstrated
      a higher melting temperature than the other two. Binding experiments with the von
      Willebrand factor A3 domain revealed the homo-trimer of (alpha1)(3) as the
      strongest binding construct, whereas the homo-trimer of (alpha2)(3) showed no
      binding. For hetero-trimers, alpha1alpha1alpha2 was found to be the strongest
      binding construct. Differences in thermal stability and binding to the A3 domain
      unambiguously demonstrate that the NC2 domain of type IX collagen determines not
      only the chain composition but also the chain register of the adjacent triple
      helix.

PMID- 23132863
TI  - Purification and characterization of a novel galloyltransferase involved in
      catechin galloylation in the tea plant (Camellia sinensis).
AB  - Catechins (flavan-3-ols), the most important secondary metabolites in the tea
      plant, have positive effects on human health and are crucial in defense against
      pathogens of the tea plant. The aim of this study was to elucidate the
      biosynthetic pathway of galloylated catechins in the tea plant. The results
      suggested that galloylated catechins were biosynthesized via 1-O-glucose ester
      dependent two-step reactions by acyltransferases, which involved two enzymes, UDP
      glucose:galloyl-1-O-beta-D-glucosyltransferase (UGGT) and a newly discovered
      enzyme, epicatechin:1-O-galloyl-beta-D-glucose O-galloyltransferase (ECGT). In
      the first reaction, the galloylated acyl donor beta-glucogallin was
      biosynthesized by UGGT from gallic acid and uridine diphosphate glucose. In the
      second reaction, galloylated catechins were produced by ECGT catalysis from beta
      glucogallin and 2,3-cis-flavan-3-ol. 2,3-cis-Flavan-3-ol and 1-O-galloyl-beta-D
      glucose were appropriate substrates of ECGT rather than 2,3-trans-flavan-3-ol and
      1,2,3,4,6-pentagalloylglucose. Purification by more than 1641-fold to apparent
      homogeneity yielded ECGT with an estimated molecular mass of 241 to 121 kDa by
      gel filtration. Enzyme activity and SDS-PAGE analysis indicated that the native
      ECGT might be a dimer, trimer, or tetramer of 60- and/or 58-kDa monomers, and
      these monomers represent a heterodimer consisting of pairs of 36- or 34- of and
      28-kDa subunits. MALDI-TOF-TOF MS showed that the protein SCPL1199 was
      identified. Epigallocatechin and epicatechin exhibited higher substrate
      affinities than beta-glucogallin. ECGT had an optimum temperature of 30  degrees
      C and maximal reaction rates between pH 4.0 and 6.0. The enzyme reaction was
      inhibited dramatically by phenylmethylsulfonyl fluoride, HgCl(2), and sodium
      deoxycholate.

PMID- 23132864
TI  - Staphylococcus aureus uses a novel multidomain receptor to break apart human
      hemoglobin and steal its heme.
AB  - Staphylococcus aureus is a leading cause of life-threatening infections in the
      United States. It requires iron to grow, which must be actively procured from its
      host to successfully mount an infection. Heme-iron within hemoglobin (Hb) is the
      most abundant source of iron in the human body and is captured by S. aureus using
      two closely related receptors, IsdH and IsdB. Here we demonstrate that each
      receptor captures heme using two conserved near iron transporter (NEAT) domains
      that function synergistically. NMR studies of the 39-kDa conserved unit from IsdH
      (IsdH(N2N3), Ala(326)-Asp(660)) reveals that it adopts an elongated dumbbell
      shaped structure in which its NEAT domains are properly positioned by a helical
      linker domain, whose three-dimensional structure is determined here in detail.
      Electrospray ionization mass spectrometry and heme transfer measurements indicate
      that IsdH(N2N3) extracts heme from Hb via an ordered process in which the
      receptor promotes heme release by inducing steric strain that dissociates the Hb
      tetramer. Other clinically significant Gram-positive pathogens capture Hb using
      receptors that contain multiple NEAT domains, suggesting that they use a
      conserved mechanism.

PMID- 23132865
TI  - Transmembrane topology and oligomeric structure of the high-affinity choline
      transporter.
AB  - The high-affinity choline transporter CHT1 mediates choline uptake essential for
      acetylcholine synthesis in cholinergic nerve terminals. CHT1 belongs to the
      Na(+)/glucose cotransporter family (SLC5), which is postulated to have a common
      13-transmembrane domain core; however, no direct experimental evidence for CHT1
      transmembrane topology has yet been reported. We examined the transmembrane
      topology of human CHT1 using cysteine-scanning analysis. Single cysteine residues
      were introduced into the putative extra- and intracellular loops and probed for
      external accessibility for labeling with a membrane-impermeable, sulfhydryl
      specific biotinylating reagent in intact cells expressing these mutants. The
      results provide experimental evidence for a topological model of a 13
      transmembrane domain protein with an extracellular amino terminus and an
      intracellular carboxyl terminus. We also constructed a three-dimensional homology
      model of CHT1 based on the crystal structure of the bacterial Na(+)/galactose
      cotransporter, which supports our conclusion of CHT1 transmembrane topology.
      Furthermore, we examined whether CHT1 exists as a monomer or oligomer. Chemical
      cross-linking induces the formation of a higher molecular weight form of CHT1 on
      the cell surface in HEK293 cells. Two different epitope-tagged CHT1 proteins
      expressed in the same cells can be co-immunoprecipitated. Moreover, co-expression
      of an inactive mutant I89A with the wild type induces a dominant-negative effect
      on the overall choline uptake activity. These results indicate that CHT1 forms a
      homo-oligomer on the cell surface in cultured cells.

PMID- 23132866
TI  - p21-Activated kinase 6 (PAK6) inhibits prostate cancer growth via phosphorylation
      of androgen receptor and tumorigenic E3 ligase murine double minute-2 (Mdm2).
AB  - The androgen receptor (AR) signaling pathway plays a crucial role in the
      development and growth of prostate malignancies. Regulation of AR homeostasis in
      prostate tumorigenesis has not yet been fully characterized. In this study, we
      demonstrate that p21-activated kinase 6 (PAK6) inhibits prostate tumorigenesis by
      regulating AR homeostasis. First, we demonstrated that in normal prostate
      epithelium, AR co-localizes with PAK6 in the cytoplasm and translocates into the
      nucleus in malignant prostate. Furthermore, AR phosphorylation at Ser-578 by PAK6
      promotes AR-E3 ligase murine double minute-2 (Mdm2) association, causing AR
      degradation upon androgen stimuli. We also showed that PAK6 phosphorylates Mdm2
      on Thr-158 and Ser-186, which is critical for AR ubiquitin-mediated degradation.
      Moreover, we found that Thr-158 collaborates with Ser-186 for AR-Mdm2 association
      and AR ubiquitin-mediated degradation as it facilitates PAK6-mediated AR
      homeostasis. PAK6 knockdown promotes prostate tumor growth in vivo.
      Interestingly, we found a strong inverse correlation between PAK6 and AR
      expression in the cytoplasm of prostate cancer cells. These observations indicate
      that PAK6 may be important for the maintenance of androgen-induced AR signaling
      homeostasis and in prostate malignancy, as well as being a possible new
      therapeutic target for AR-positive and hormone-sensitive prostate cancer.

PMID- 23132867
TI  - A novel mode of regulation of the Staphylococcus aureus catabolite control
      protein A (CcpA) mediated by Stk1 protein phosphorylation.
AB  - The Staphylococcus aureus serine/threonine protein kinase Stk1 (also known as
      PknB) affects different key pathways such as cell wall metabolism, antibiotic
      susceptibility, and regulation of virulence. Here we report that the catabolite
      control protein A (CcpA), a highly conserved regulator of carbon catabolite
      repression and virulence in a number of gram-positive pathogens, was efficiently
      phosphorylated in vitro and in vivo by Stk1 in S. aureus, whereas the CcpA
      homologues of Bacillus subtilis and Bacillus anthracis were not affected by the
      Stk1 orthologue PrkC. Mass spectrometry and mutational analyses identified Thr-18
      and Thr-33 as the phosphoacceptors; both are located in the DNA binding domain of
      this protein. Electrophoretic mobility shift assays demonstrated that the CcpA
      DNA binding activity was completely abrogated for the phosphorylated CcpA. The
      physiological relevance of CcpA phosphorylation was assessed by generating CcpA
      phosphoablative (T18A/T33A) or phosphomimetic (T18D/T33D) mutants. In contrast to
      the wild-type and phosphoablative ccpA alleles, introduction of the
      phosphomimetic ccpA allele in a DeltaccpA mutant failed to restore the parental
      biofilm formation profile and the transcription of citZ and hla to levels seen
      with the wild type. The strong up regulation of ccpA transcripts and CcpA level
      in the ccpA mutant trans-complemented with the phosphomimetic CcpA variant
      suggest furthermore that CcpA acts as a negative regulator of its own expression.
      Together, these findings demonstrate that Stk1-driven phosphorylation of CcpA
      inhibits its DNA binding activity toward its regulon in S. aureus, representing a
      novel regulatory mechanism of CcpA activity in addition to the well known
      regulation via HprKP/Hpr in this clinically important pathogen.

PMID- 23132869
TI  - Mental health-care provision for marginalized groups across Europe: findings from
      the PROMO study.
AB  - BACKGROUND: Providing mental health care to socially marginalized groups is a
      challenge. There is limited evidence on what form of mental health-care generic
      (i.e. not targeting a specific social group) and group-specific services provide
      to socially marginalized groups in Europe. AIM: To describe the characteristics
      of services providing mental health care for people with mental disorders from
      socially marginalized groups in European capitals. METHODS: In two highly
      deprived areas in different European capital cities, services providing some form
      of mental health care for six marginalized groups, i.e. homeless, street sex
      workers, asylum seekers/refugees, irregular migrants, travelling communities and
      long-term unemployed, were identified and contacted. Data were obtained on
      service characteristics, staff and programmes. RESULTS: In 8 capital cities, 516
      out of 575 identified services were assessed (90%); 297 services were generic (18
      79 per city) and 219 group-specific (13-50). All cities had group-specific
      services for the homeless, street sex workers and asylum seekers/refugees.
      Generic services provided more health-care programmes. Group-specific services
      provided more outreach programmes and social care. There was a substantial
      overlap in the programmes provided by the two types of services. CONCLUSIONS: In
      deprived areas of European capitals, a considerable number of services provide
      mental health care to socially marginalized groups. Access to these services
      often remains difficult. Group-specific services have been widely established,
      but their role overlaps with that of generic services. More research and
      conceptual clarity on the function of group-specific services are required.

PMID- 23132868
TI  - Disease-associated mutations in the prion protein impair laminin-induced process
      outgrowth and survival.
AB  - Prions, the agents of transmissible spongiform encephalopathies, require the
      expression of prion protein (PrP(C)) to propagate disease. PrP(C) is converted
      into an abnormal insoluble form, PrP(Sc), that gains neurotoxic activity.
      Conversely, clinical manifestations of prion disease may occur either before or
      in the absence of PrP(Sc) deposits, but the loss of normal PrP(C) function
      contribution for the etiology of these diseases is still debatable. Prion disease
      associated mutations in PrP(C) represent one of the best models to understand the
      impact of PrP(C) loss-of-function. PrP(C) associates with various molecules and,
      in particular, the interaction of PrP(C) with laminin (Ln) modulates neuronal
      plasticity and memory formation. To assess the functional alterations associated
      with PrP(C) mutations, wild-type and mutated PrP(C) proteins were expressed in a
      neural cell line derived from a PrP(C)-null mouse. Treatment with the laminin
      gamma1 chain peptide (Ln gamma1), which mimics the Ln binding site for PrP(C),
      increased intracellular calcium in cells expressing wild-type PrP(C), whereas a
      significantly lower response was observed in cells expressing mutated PrP(C)
      molecules. The Ln gamma1 did not promote process outgrowth or protect against
      staurosporine-induced cell death in cells expressing mutated PrP(C) molecules in
      contrast to cells expressing wild-type PrP(C). The co-expression of wild-type
      PrP(C) with mutated PrP(C) molecules was able to rescue the Ln protective
      effects, indicating the lack of negative dominance of PrP(C) mutated molecules.
      These results indicate that PrP(C) mutations impair process outgrowth and
      survival mediated by Ln gamma1 peptide in neural cells, which may contribute to
      the pathogenesis of genetic prion diseases.

PMID- 23132870
TI  - Physical activity in England: who is meeting the recommended level of
      participation through sports and exercise?
AB  - BACKGROUND: Little is known about the correlates of meeting recommended levels of
      participation in physical activity (PA) and how this understanding informs public
      health policies on behaviour change. OBJECTIVE: To analyse who meets the
      recommended level of participation in PA in males and females separately by
      applying 'process' modelling frameworks (single vs. sequential 2-step process).
      METHODS: Using the Health Survey for England 2006, (n = 14 142; >= 16 years),
      gender-specific regression models were estimated using bivariate probit with
      selectivity correction and single probit models. A 'sequential, 2-step process'
      modelled participation and meeting the recommended level separately, whereas the
      'single process' considered both participation and level together. RESULTS: In
      females, meeting the recommended level was associated with degree holders
      [Marginal effect (ME) = 0.013] and age (ME = -0.001), whereas in males, age was a
      significant correlate (ME = -0.003 to -0.004). The order of importance of
      correlates was similar across genders, with ethnicity being the most important
      correlate in both males (ME = -0.060) and females (ME = -0.133). In females, the
      'sequential, 2-step process' performed better (rho = -0.364, P < 0.001) than that
      in males (rho = 0.154). CONCLUSION: The degree to which people undertake the
      recommended level of PA through vigorous activity varies between males and
      females, and the process that best predicts such decisions, i.e. whether it is a
      sequential, 2-step process or a single-step choice, is also different for males
      and females. Understanding this should help to identify subgroups that are less
      likely to meet the recommended level of PA (and hence more likely to benefit from
      any PA promotion intervention).

PMID- 23132871
TI  - An ethical framework for the prevention of overweight and obesity: a tool for
      thinking through a programme's ethical aspects.
AB  - INTRODUCTION: It is important to be aware of the ethical pitfalls in programmes
      to prevent overweight and obesity, such as stigmatization, blaming the victim and
      reinforcement of health inequalities. In this article, we present an ethical
      framework for facilitating a structured analysis to the extent to which a
      programme prevents overweight or obesity is ethically acceptable. METHODS: First,
      we made an inventory of ethical issues in programmes to prevent overweight and
      obesity. Secondly, we studied the available ethical frameworks that address the
      area of public health. Finally, we designed an ethical framework for the
      prevention of overweight and obesity, which was tested in two international
      workshops. RESULTS: At the heart of the framework is a list of eight questions on
      the morally relevant features of a programme: its effects on physical health,
      psychosocial well-being, informed choice, cultural values, equality, privacy,
      responsibility and liberty. Answering these questions provides a map of the
      potential ethical pitfalls of a specific programme. This mapping should be
      followed by a structured discussion of the arguments and their importance, and
      the decision whether, and if so under what conditions, the programme should be
      implemented. CONCLUSION: Considering the ethical aspects of the programmes to
      prevent obesity or overweight is extremely important in the face of the urgent
      and extensive health problem of overweight and obesity. Our framework is a
      practical tool for systematic ethical evaluation. It is applicable to a broad
      range of programmes in different stages of development and implementation.

PMID- 23132872
TI  - Adolescent perspectives on wearing accelerometers to measure physical activity in
      population-based trials.
AB  - BACKGROUND: Accelerometers are increasingly used in health research to measure
      physical activity, but few published studies document participants' views and
      experiences of wearing accelerometers, preferring to focus on measurement
      decisions and outcomes, and fewer still have reported the views and experiences
      of adolescent participants. PURPOSE: The purpose of this study is to examine the
      use of accelerometers with young people including recruitment, retention and
      adherence to protocol. METHODS: The AHEAD (Activity and Healthy Eating in
      Adolescence) feasibility study, involving over 1000 students aged 12/13 years,
      took place in south-west England between 2007 and 2009. Piloting work was
      followed by an exploratory trial, incorporating a process evaluation, in six
      schools. Students were asked to wear accelerometers for 7 days at baseline and
      follow-up. RESULTS: Eighty-nine percent of students provided some accelerometer
      data at baseline and 87% at follow-up. However, adherence (recording >= 600
      minutes per day for >= 3 days) fell from 75% at baseline to 56% at follow-up.
      Factors affecting adherence included the following: the use and type of
      incentives, appearance, discomfort and unforeseen changes to the school
      timetable. CONCLUSIONS: If worn properly, accelerometers can provide an important
      objective measure of physical activity in population-based studies promoting
      physical activity. But to achieve generalizable results, it is important to
      maximize recruitment, retention and adherence to protocol across the study
      population. For adolescents, adherence may be improved by the following: a 'two
      part' reward (part one for returns, part two for adherence), personal activity
      graphs, and less obtrusive belts and monitors.

PMID- 23132873
TI  - The family's economic resources and adolescents' health complaints--do
      adolescents' own economic resources matter?
AB  - BACKGROUND: The present study focuses on the relevance of economic resources to
      psychological and psychosomatic health complaints during adolescence. It explores
      the link between the family's and the adolescent's economic resources and
      investigates whether or not differences in health complaints by the family's
      financial situation can be explained by adolescents' own economic resources.
      METHODS: Drawing on data from two Swedish surveys on living conditions during
      adolescence (in the age group 10-18 years) conducted in 2002-03, logistic
      regressions were used to assess the associations between adolescents' own and
      household economic resources on two measures of health complaints. RESULTS: The
      association between family economic hardship (i.e. lack of cash margin) and
      adolescents' health complaints largely disappeared when controlling for
      adolescents' own economic resources. Three measures of own absolute and relative
      economic resources were used. Out of these, the ability (or not) to buy things
      that others have was connected with both psychological [Odds ratio (OR) 2.16, 95%
      confidence interval (95% CI) 1.6-2.9] and psychosomatic complaints (OR 1.67, 95%
      CI 1.3-2.1), irrespective of age and gender. The importance of lacking a personal
      cash margin or not being able to join friends seemed to differ between age groups
      and genders. CONCLUSIONS: The importance of different aspects of economic
      resources seems to vary across age groups and gender. However, not being able to
      buy things that others have was clearly associated with health complaints
      irrespective of age and gender. Family economic hardship was associated with
      adolescents' health complaints, and this association was largely explained by
      adolescents' own economic resources.

PMID- 23132874
TI  - Changing epidemiology of hepatitis B and migration--a comparison of six Northern
      and North-Western European countries.
AB  - BACKGROUND: Increased migration volume and different Hepatitis B prevalence
      between immigration and emigration countries have changed the Hepatitis B virus
      (HBV) epidemiology considerably in Northern and North-Western European migrants
      receiving countries. Due to the difference in migration status monitoring, the
      HBV infection data on migrants are not easily comparable among those countries.
      The study aims were: to compare the migration status indicators used by the
      national surveillance system in six Northern and North-Western European countries
      (the Netherlands, Germany, Finland, Denmark, Sweden and the UK); to determine the
      impact of the migration status on HBV infection by comparing the available data
      on prevalence and transmission routes of Hepatitis B in the migration and the
      general population in the six countries; to recommend sensible indicators and
      pertinent measures for HBV infection surveillance and control in the region.
      METHODS: Literature review, statistical data analysis on migration and HBV
      infection in the six countries; expert interviews to identify migration status
      indicators used in national surveillance systems. RESULTS: Evident differences
      were found between the migration and the general population in Hepatitis B
      prevalence and transmission routes in the six countries. Migration status is
      monitored differently in six surveillance systems; immigrants from
      high/intermediate Hepatitis B endemic countries constitute a substantial
      proportion of HBsAg(+) and chronic cases in all six countries. CONCLUSIONS:
      International migration has an obvious impact on Hepatitis B prevalence in the
      six countries. It is important to include common migration status indicators and
      to collect comparable data for HBV infection surveillance in different
      notification systems.

PMID- 23132875
TI  - Three-year effects on dietary quality of health education: a randomized
      controlled trial of people with screen-detected dysglycaemia (The ADDITION study,
      Denmark).
AB  - BACKGROUND: Healthy diet is a core component in prevention and self-management of
      type 2 diabetes and cardiovascular disease. The long-term efficacy was assessed
      of a theory-based health education programme 'Ready to Act' on dietary quality in
      people with screen-detected dysglycaemia. METHODS: Five hundred and nine adults
      with prediabetes (impaired glucose tolerance, impaired fasting glycaemia) or type
      2 diabetes were recruited through screening for type 2 diabetes [the ADDITION
      (Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected
      Diabetes in Primary Care) study, DK] and then randomly assigned to health
      education or to a control group (I = 322; C = 187). The intervention group was
      offered a 12-week programme in health-related action competence including 2 one
      to-one and 8 group sessions (18 h). Dietary quality was measured by the Dietary
      Quality Score_revised (0-8 points) at baseline and at one- and 3-year follow-up.
      Changes were analysed by multilevel analyses. RESULTS: The analysis included data
      from 444 participants (87%). At the 3-year follow-up, the intervention group had
      significantly increased dietary quality compared with the control group (net
      change: 0.39 Dietary Quality Score_revised points, P = 0.04). The intake of
      unsaturated fats used on bread and for cooking increased in the intervention
      group compared with the control group at the 3-year follow-up (net change: 31
      g/week; P = 0.02). A non-significant tendency toward an increased intake of
      vegetables in the intervention group compared with the control group was seen
      (net change: 111 g/week; P = 0.16). No changes were seen in fish intake.
      CONCLUSIONS: Health education aiming at action competence improved the long-term
      dietary quality in a population with dysglycaemia, especially according to the
      intake of unsaturated fat. The ADDITION trial was registered at
      ClinicalTrials.gov ID no NCT00237549.

PMID- 23132876
TI  - Should we invest in environmental interventions to encourage physical activity in
      England? An economic appraisal.
AB  - BACKGROUND: The Department of Health in England asked the National Institute for
      Health and Clinical Excellence (NICE) to develop guidance on environmental
      interventions that promote physical activity. The economic appraisals summarized
      in this study informed the development of that guidance. In view of the
      difficulties inherent in applying conventional health economic evaluation
      techniques to public health interventions, the economic appraisal employed a
      multi-faceted approach. METHODS: The analyses comprised of three components. Two
      cost-utility analyses; the first used a life-time disease progression model which
      sought to take into account the long-term benefits of physical activity on health
      outcomes, whereas the second used data from a regression analysis which captured
      some of the short-term, process benefits of physical activity which might
      manifest themselves in terms of improved mental health and wellbeing. The third
      approach was a cost-benefit analysis that took into account benefits beyond
      healthcare. RESULTS: The cost-utility approaches generated cost-effectiveness
      estimates ranging between L100 and L10 000 per QALY depending on the level of
      effectiveness of the intervention and the proportion of the intervention cost
      that was deemed to be attributable to health. The standardized cost-benefit ratio
      was 11:1. CONCLUSION: The findings present a consistent case to support
      environmental interventions that promote increased physical activity in the
      sedentary adult population. However, some degree of caution should be taken in
      interpreting the findings due to the limitations of the evidence upon which they
      are based. Further consideration should also be given to the relative merits of
      alternative approaches to assessing the value of changes to the built environment
      that might also benefit health as a positive externality.

PMID- 23132877
TI  - The mental health risks of economic crisis in Spain: evidence from primary care
      centres, 2006 and 2010.
AB  - BACKGROUND: Nearly all European countries have been affected by the economic
      crisis that began in 2007, but the consequences have been among the worst in
      Spain. We investigated the associations of the recession on the frequency of
      mood, anxiety, somatoform, alcohol-related and eating disorders among those
      visiting Spanish primary care settings. METHODS: Primary care physicians selected
      randomized samples of patients attending primary care centres representing
      Spain's consulting populations. A total of 7940 patients in 2006-07 and 5876 in
      2010-11 were administered the Primary Care Evaluation of Mental Disorders (PRIME
      MD) instrument to diagnose mental disorders. Multivariate logistic regression
      models were used to quantify overall changes in the frequency of mental
      disorders, adjusting for potential socio-demographic differences in consulting
      populations unrelated to economic factors. RESULTS: Compared with the pre-crisis
      period of 2006, the 2010 survey revealed substantial and significant increases in
      the proportion of patients with mood (19.4% in major depression), anxiety (8.4%
      in generalized anxiety disorder), somatoform (7.3%) and alcohol-related disorders
      (4.6% in alcohol dependence), all significant at P < 0.001, but not in eating
      disorders (0.15%, P = 0.172). Independent of observed risks of unemployment [odds
      ratio (OR) = 1.72, P < 0.001], we observed a significantly elevated risk of major
      depression associated with mortgage repayment difficulties (OR = 2.12, P < 0.001)
      and evictions (OR = 2.95, P < 0.001). About one-third of the overall risk in the
      consulting population's attendance with mental health disorders could be
      attributed to the combined risks of household unemployment and mortgage payment
      difficulties. CONCLUSION: Recession has significantly increased the frequency of
      mental health disorders and alcohol abuse among primary care attendees in Spain,
      particularly among families experiencing unemployment and mortgage payment
      difficulties.

PMID- 23132878
TI  - The accuracy of self-reported data concerning recent cannabis use in the French
      armed forces.
AB  - BACKGROUND: The aims were to evaluate the accuracy of self-report of past-month
      cannabis use in a representative sample of French military staff members and to
      evaluate the scale of the prevarication bias. METHOD: Data from three cross
      sectional surveys conducted between 2005 and 2008 (n = 3493) were used. The
      characteristics of self-report (sensitivity, specificity, positive predictive
      value and negative predictive value) were computed using tetrahydrocannabinol
      detection in urine as the reference. RESULTS: The prevalence for past-month
      cannabis use was 16.1% and for positive testing was 13.4%. The discriminant power
      of self-report was good, with an area under the receiver operating
      characteristics curve 0.90. Specificity (94.5%) and negative predictive values
      (97.8%) were good, but sensitivity (85.7%) and positive predictive values (70.4%)
      were lower. The lowest sensitivity values were observed in the higher categories
      of personnel and in the Navy, which could reflect some prevarication in these sub
      populations who might believe they were more exposed to sanctions if detected.
      CONCLUSIONS: Despite certain limitations of urine analysis as a reference,
      because of its poor detection of occasional users, our study is in favour of good
      accuracy of self-reported data on cannabis use, even among the military. However,
      our results, derived from a population study, do not enable any assumptions on
      the validity of self-reported data collected during individual testing procedures
      for the purpose of improving occupational safety.

PMID- 23132890
TI  - Incorporating patients' preferences into medical decision making.
AB  - Current models of care emphasize the importance of including patients' values in
      the decision-making process. This is particularly important for decisions for
      which there are few data supporting a clear strategy or treatment choice.
      Constructing preferences for complex decisions requires that patients be able to
      consider multiple trade-offs between specific risks and benefits. Several
      marketing research techniques have been recently applied to heath care settings
      to facilitate this process. Most can be programmed to generate patients'
      preferences or priorities, which can then be used to improve patient-physician
      communication. In this article, we will describe some of the currently available
      approaches that have been successfully used in the health care setting. We
      provide case examples to illustrate the potential value of adopting each of these
      approaches in clinical practice.

PMID- 23132891
TI  - Conceptual, methodological, and ethical problems in communicating uncertainty in
      clinical evidence.
AB  - The communication of uncertainty in clinical evidence is an important endeavor
      that poses difficult conceptual, methodological, and ethical problems. Conceptual
      problems include logical paradoxes in the meaning of probability and "ambiguity"-
      second-order uncertainty arising from the lack of reliability, credibility, or
      adequacy of probability information. Methodological problems include questions
      about optimal methods for representing fundamental uncertainties and for
      communicating these uncertainties in clinical practice. Ethical problems include
      questions about whether communicating uncertainty enhances or diminishes patient
      autonomy and produces net benefits or harms. This article reviews the limited but
      growing literature on these problems and efforts to address them and identifies
      key areas of focus for future research. It is argued that the critical need
      moving forward is for greater conceptual clarity and consistent representational
      methods that make the meaning of various uncertainties understandable, and for
      clinical interventions to support patients in coping with uncertainty in decision
      making.

PMID- 23132892
TI  - A randomized experiment investigating the suitability of speech-enabled IVR and
      Web modes for publicly reported surveys of patients' experience of hospital care.
AB  - The HCAHPS Survey obtains hospital patients' experiences using four modes: Mail
      Only, Phone Only, Mixed (mail/phone follow-up), and Touch-Tone (push-button)
      Interactive Voice Response with option to transfer to live interviewer (TT
      IVR/Phone). A new randomized experiment examines two less expensive modes:
      Web/Mail (mail invitation to participate by Web or request a mail survey) and
      Speech-Enabled IVR (SE-IVR/Phone; speaking to a voice recognition system;
      optional transfer to an interviewer). Web/Mail had a 12% response rate (vs. 32%
      for Mail Only and 33% for SE-IVR/Phone); Web/Mail respondents were more educated
      and less often Black than Mail Only respondents. SE-IVR/Phone respondents (who
      usually switched to an interviewer) were less often older than 75 years, more
      often English-preferring, and reported better care than Mail Only respondents.
      Concerns regarding inconsistencies across implementations, low adherence to
      primary modes, or low response rate may limit the applicability of the SE
      IVR/Phone and Web/Mail modes in HCAHPS and similar standardized environments.

PMID- 23132893
TI  - Use of electronic patient records for research: views of patients and staff in
      general practice.
AB  - BACKGROUND: Electronic patient records offer unique opportunities to undertake
      population-based research. The Health Research Support Service (HRSS) pilot
      project sought to extract electronic records on a national basis from across
      health and social care and transfer them together with identifiers to a
      designated 'safe haven'. OBJECTIVE: To determine the feasibility and
      acceptability of the HRSS pilot in primary care. METHODS: Interviews and focus
      groups with patients and practice staff. RESULTS: There was general support from
      both patients and staff for the principle of the HRSS. The 'opt-out' basis for
      participation in the HRSS drew mixed responses from patients and staff, with an
      appreciation of the advantages in relation to participation by default, but
      concerns about the extent to which this constituted true consent. Concerns were
      expressed about confidentiality and the safety and security of the extracted
      data. The patient information pack was roundly criticized by both patients and
      staff. Trust in individual GPs, practices and the National Health Service (NHS)
      was a crucial factor in patients' decisions about participation. CONCLUSIONS:
      Although patients and staff were generally supportive of the HRSS, they require
      clear information about the proposed use of medical records for research
      purposes. The question of 'opt out' versus 'opt in' remains controversial and
      further consideration will be needed if research using routine medical records is
      to achieve its full potential as a 'core' activity in the NHS.

PMID- 23132894
TI  - Frequency of medication errors in primary care patients with polypharmacy.
AB  - BACKGROUND: Chronic diseases affect more than half of the population >=75 years
      of age in developed countries. Prescription medication use increases with age.
      Depending on definition, 25-80% of elderly are exposed to polypharmacy.
      Polypharmacy increases the risk of hospitalization, interactions and adverse drug
      reactions. OBJECTIVE: To examine the frequency of medication errors in patients
      with polypharmacy treated in general practice. METHODS: The medications of 169
      patients with polypharmacy treated in 22 GP surgeries in Austria were analysed.
      The analysis identified (i) medication errors, including non-evidence-based
      medications, dosing errors and potentially dangerous interactions in all patients
      and (ii) potentially inappropriate medications (PIMs) in the subgroup of elderly
      patients (>=65 years). RESULTS: The patients took on average 9.1+/-3.0
      medications per day. The maximum, in one patient, was 20 medications per day.
      Some 93.5% had at least one non-evidence-based medication. On average, 2.7+/-1.66
      medications per patient were found to be not indicated. At least one dosing error
      was found in 56.2% of all patients. One potential interaction of the most severe
      degree (category X interaction) was detected in 1.8% (n = 3) and two such
      interactions in 0.6% (n = 1). These combinations should have been avoided. Of the
      169 patients, 158 were elderly (>=65 years). Of these seniors, 37.3% (n = 59) had
      at least one PIM according to the PRISCUS list for the elderly. CONCLUSION: The
      frequency of medication errors is high in patients with polypharmacy in primary
      care. Development of strategies (e.g. external medication review) is required to
      counteract medication errors.

PMID- 23132895
TI  - An unusual swelling on an infant's head.

PMID- 23132896
TI  - Patterns of genomic differentiation between ecologically differentiated M and S
      forms of Anopheles gambiae in West and Central Africa.
AB  - Anopheles gambiae M and S are thought to be undergoing ecological speciation by
      adapting to different larval habitats. Toward an improved understanding of the
      genetic determinants and evolutionary processes shaping their divergence, we used
      a 400,000 single-nucleotide polymorphism (SNP) genotyping array to characterize
      patterns of genomic differentiation between four geographically paired M and S
      population samples from West and Central Africa. In keeping with recent studies
      based on more limited genomic or geographic sampling, divergence was not confined
      to a few isolated "speciation islands." Divergence was both widespread across the
      genome and heterogeneous. Moreover, we find consistent patterns of genomic
      divergence across sampling sites and mutually exclusive clustering of M and S
      populations using genetic distances based on all 400,000 SNPs, implying that M
      and S are evolving collectively across the study area. Nevertheless, the
      clustering of local M and S populations using genetic distances based on SNPs
      from genomic regions of low differentiation is consistent with recent gene flow
      and introgression. To account for these data and reconcile apparent paradoxes in
      reported patterns of M-S genomic divergence and hybridization, we propose that
      extrinsic ecologically based postmating barriers vary in strength as
      environmental conditions fluctuate or change.

PMID- 23132897
TI  - Estimating the rate of irreversibility in protein evolution.
AB  - Whether or not evolutionary change is inherently irreversible remains a
      controversial topic. Some examples of evolutionary irreversibility are known;
      however, this question has not been comprehensively addressed at the molecular
      level. Here, we use data from 221 human genes with known pathogenic mutations to
      estimate the rate of irreversibility in protein evolution. For these genes, we
      reconstruct ancestral amino acid sequences along the mammalian phylogeny and
      identify ancestral amino acid states that match known pathogenic mutations. Such
      cases represent inherent evolutionary irreversibility because, at the present
      moment, reversals to these ancestral amino acid states are impossible for the
      human lineage. We estimate that approximately 10% of all amino acid substitutions
      along the mammalian phylogeny are irreversible, such that a return to the
      ancestral amino acid state would lead to a pathogenic phenotype. For a subset of
      51 genes with high rates of irreversibility, as much as 40% of all amino acid
      evolution was estimated to be irreversible. Because pathogenic phenotypes do not
      resemble ancestral phenotypes, the molecular nature of the high rate of
      irreversibility in proteins is best explained by evolution with a high prevalence
      of compensatory, epistatic interactions between amino acid sites. Under such mode
      of protein evolution, once an amino acid substitution is fixed, the probability
      of its reversal declines as the protein sequence accumulates changes that affect
      the phenotypic manifestation of the ancestral state. The prevalence of epistasis
      in evolution indicates that the observed high rate of irreversibility in protein
      evolution is an inherent property of protein structure and function.

PMID- 23132899
TI  - Stichoposide C induces apoptosis through the generation of ceramide in leukemia
      and colorectal cancer cells and shows in vivo antitumor activity.
AB  - PURPOSE: Marine triterpene glycosides that are physiologically active natural
      compounds isolated from sea cucumbers (holothurians) and sponges have antifungal,
      cytotoxic, and antitumor activities, whose specific molecular mechanisms remain
      to be elucidated. In this study, we examined if and through which mechanisms
      stichoposide C (STC) from Thelenota anax (family Stichopodidae) induces apoptosis
      in leukemia and colorectal cancer cells. EXPERIMENTAL DESIGN: We examined STC
      induced apoptosis in human leukemia and colorectal cancer cells in the context of
      mitochondrial injury and signaling pathway disturbances, and investigated the
      antitumor effect of STC in mouse CT-26 subcutaneous tumor and HL-60 leukemia
      xenograft models. RESULTS: We found that STC induces apoptosis in these cells in
      a dose-dependent manner and leads to the activation of Fas and caspase-8,
      cleavage of Bid, mitochondrial damage, and activation of caspase-3. STC activates
      acid sphingomyelinase (SMase) and neutral SMase, which resulted in the generation
      of ceramide. Specific inhibition of acid SMase or neutral SMase and siRNA
      knockdown experiments partially blocked STC-induced apoptosis. Moreover, STC
      markedly reduced tumor growth of HL-60 xenograft and CT-26 subcutaneous tumors
      and increased ceramide generation in vivo. CONCLUSIONS: Ceramide generation by
      STC, through activation of acid and neutral SMase, may in part contribute to STC
      induced apoptosis and antitumor activity. Thus, STC may have therapeutic
      relevance for human leukemia and colorectal cancer.

PMID- 23132901
TI  - Derivation of background mortality by smoking and obesity in cancer simulation
      models.
AB  - BACKGROUND: Simulation models designed to evaluate cancer prevention strategies
      make assumptions on background mortality-the competing risk of death from causes
      other than the cancer being studied. Researchers often use the U.S. life tables
      and assume homogeneous other-cause mortality rates. However, this can lead to
      bias because common risk factors such as smoking and obesity also predispose
      individuals for deaths from other causes such as cardiovascular disease. METHODS:
      We obtained calendar year-, age-, and sex-specific other-cause mortality rates by
      removing deaths due to a specific cancer from U.S. all-cause life tables.
      Prevalence across 12 risk factor groups (3 smoking [never, past, and current
      smoker] and 4 body mass index [BMI] categories [<25, 25-30, 30-35, 35+ kg/m(2)])
      were estimated from national surveys (National Health and Nutrition Examination
      Surveys [NHANES] 1971-2004). Using NHANES linked mortality data, we estimated
      hazard ratios for death by BMI/smoking using a Poisson regression model. Finally,
      we combined these results to create 12 sets of BMI and smoking-specific other
      cause life tables for U.S. adults aged 40 years and older that can be used in
      simulation models of lung, colorectal, or breast cancer. RESULTS: We found
      substantial differences in background mortality when accounting for BMI and
      smoking. Ignoring the heterogeneity in background mortality in cancer simulation
      models can lead to underestimation of competing risk of deaths for higher-risk
      individuals (e.g., male, 60-year old, white obese smokers) by as high as 45%.
      CONCLUSION: Not properly accounting for competing risks of death may introduce
      bias when using simulation modeling to evaluate population health strategies for
      prevention, screening, or treatment. Further research is warranted on how these
      biases may affect cancer-screening strategies targeted at high-risk individuals.

PMID- 23132902
TI  - Generalized additive models for the analysis of EQ-5D utility data.
AB  - BACKGROUND: Measured utility data have a discrete distribution, and the
      discreteness is particularly pronounced for EQ-5D utilities. Given the
      discreteness of the data, modeling the distribution parametrically is likely to
      be difficult. Moreover, since the distribution is bounded, the linearity
      assumptions made by many models are questionable. This article suggests using
      semi-parametric models and illustrates the use of generalized additive models
      (GAMs) for handling nonlinear associations. METHODS: A simulation study is used
      to explore whether bias arises when applying parametric models to discrete
      utility data. A further simulation investigates the bias in semi-parametric
      linear and quasi-beta regression models when the assumed linearity does not hold
      and also investigates the use of GAMs. The use of GAMs in practice is shown
      through a recent study of health utilities among patients with diabetes. RESULTS:
      Using parametric beta models to analyze discrete EQ-5D utility data led to
      substantial bias. Both semi-parametric linear regression and quasi-beta
      regression led to biased estimates of marginal and incremental effects when the
      mean model was misspecified. The use of GAMs reduced these biases. CONCLUSIONS:
      Parametric models for EQ-5D utility data should be used with caution. Semi
      parametric modeling of utility data should check for nonlinearity. GAMs can help
      in diagnosing and accommodating nonlinearity.

PMID- 23132903
TI  - A proposed modification to the McDonald 2010 criteria for the diagnosis of
      primary progressive multiple sclerosis.
AB  - BACKGROUND: The diagnostic criteria for primary-progressive multiple sclerosis
      (PPMS) have undergone revision over the last 20 years. Cerebrospinal fluid
      oligoclonal bands (CSFOBs) have received less emphasis in recent revisions of the
      McDonald criteria. The aim of this study was to examine the sensitivity of the
      diagnostic criteria for PPMS with particular reference to spinal cord criteria
      and examine the utility of CSFOBs in a cohort of PPMS patients. METHODS: All new
      PPMS diagnoses between 1990 and 2011 were identified. Baseline clinical details
      and paraclinical evaluations including MRI of the brain, spinal cord, CSF and
      visually evoked responses (VERs) were assessed. The proportion of patients who
      met the requirements for diagnosis of PPMS on the basis of Thompson's and the
      McDonald Criteria (2001, 2005, 2010) were determined. RESULTS: There were 88/95
      PPMS patients who had at least two diagnostic investigations. The sensitivity of
      Thompson's and the McDonald 2001 criteria was 64%; the McDonald 2010 revisions
      gave the highest sensitivity (77%); the McDonald 2005 criteria had intermediate
      sensitivity (74%). The combination of CSFOBs and MRI of the brain yielded the
      greatest number of patients demonstrating dissemination in space (DIS) on only
      two investigations. VERs did not aid diagnosis. Reducing requirements for the
      number of spinal cord lesions (symptomatic or not) to one increased diagnostic
      sensitivity to 84%. CONCLUSION: An alternative criterion requiring two of: i) MRI
      of the brain with one or more lesions in two of three regions typical for
      demyelination; ii) the presence of one T2-weighted spinal cord plaque (typical
      for demyelination); iii) CSFOBs; would increase the diagnostic sensitivity for
      PPMS.

PMID- 23132904
TI  - Exercise in the community for people with multiple sclerosis--a follow-up of
      people with minimal gait impairment.
AB  - BACKGROUND: Although there are many studies evaluating exercise interventions,
      few studies have evaluated the effect at follow-up. OBJECTIVES: This paper
      presents follow-up data for participants who completed the exercise interventions
      in a large randomised controlled trial. METHODS: One hundred twenty-one people
      with multiple sclerosis (MS) with minimal gait impairment who completed 10 weeks
      of community-based exercise interventions were evaluated by a blinded assessor 12
      weeks after the intervention. The primary outcome measure was the Multiple
      Sclerosis Impact Scale-29 version 2 (MSIS-29,v2) physical component. Other
      outcomes were the MSIS-29 psychological component, the Modified Fatigue Impact
      Scale (MFIS) and the 6-minute walk test (6MWT) distance. RESULTS: The positive
      effect on the physical impact of MS was not maintained from baseline to follow-up
      (-1.6, 95% CI -0.8, 4.0, p=0.189). The psychological impact and the impact of
      fatigue remained significantly improved (-3.5, 95% CI -6.1, -1.0, p = 0.006 and 
      4.68, 95% CI -6.9, -2.5, p < 0.001, respectively). There was no time effect for
      the 6MWT (f = 1.76, p = 0.179) although the trend suggests reversal of the
      benefits gained from the physiotherapist (PT)- and fitness instructor (FI)-led
      intervention. CONCLUSION: The maintained benefit on the psychological impact of
      MS and fatigue may have important personal and socioeconomic consequences;
      however, it is important to find ways to maintain the physical benefits of
      exercise over the long term.

PMID- 23132905
TI  - New insights into the early steps of oil body mobilization during pollen
      germination.
AB  - In some plants, pollen grains accumulate storage lipids that serve as energy
      supply during germination. Here, three enzymes involved in early steps of oil
      body mobilization in the male gametophyte were functionally characterized for the
      first time. The effect of extracellular sugars on pollen performance and oil body
      dynamics was also analysed. Olive pollen oil bodies showed phospholipase A,
      lipase, and lipoxygenase activities on their surface. Enzyme activity levels
      increased during germination with a maximum after 3h. Removal of extracellular
      sugars from the germination medium did not affect pollen performance but
      increased enzyme activity rates and sped up oil body mobilization. Inhibitors
      seriously hampered pollen germination and pollen tube growth, leading to a
      characteristic accumulation of oil bodies in the germinative aperture. It can be
      concluded that storage lipids are sufficient for proper olive pollen germination.
      A lipase and a lipoxygenase are likely involved in oil body mobilization.
      Extracellular sugars may modulate their function, while a phospholipase A may
      promote their access to the storage lipids.

PMID- 23132907
TI  - Phylogeographical pattern and evolutionary history of an important Peninsular
      Malaysian timber species, Neobalanocarpus heimii (Dipterocarpaceae).
AB  - Tectonic movements, climatic oscillations, and marine transgressions during the
      Cenozoic have had a dramatic effect on the biota of the tropical rain forest.
      This study aims to reveal the phylogeography and evolutionary history of a
      Peninsular Malaysian endemic tropical timber species, Neobalanocarpus heimii
      (Dipterocarpaceae). A total of 32 natural populations of N. heimii, with 8
      samples from each population were investigated. Fifteen haplotypes were
      identified from five noncoding chloroplast DNA (cpDNA) regions. Overall, two
      major genealogical cpDNA lineages of N. heimii were elucidated: a widespread
      southern and a northern region. The species is predicted to have survived in
      multiple refugia during climatic oscillations: the northwestern region (R1), the
      northeastern region (R2), and the southern region (R3). These putative glacial
      refugia exhibited higher levels of genetic diversity, population differentiation,
      and the presence of unique haplotypes. Recolonization of refugia R1 and R2 could
      have first expanded into the northern region and migrated both northeastwards and
      northwestwards. Meanwhile, recolonization of N. heimii throughout the southern
      region could have commenced from refugia R3 and migrated toward the northeast and
      northwest, respectively. The populations of Tersang, Pasir Raja, and Rotan
      Tunggal exhibited remarkably high haplotype diversity, which could have been the
      contact zones that have received an admixture of gene pools from the northerly
      and also southerly regions. As a whole, the populations of N. heimii derived from
      glacial refugia and contact zones should be considered in the conservation
      strategies in order to safeguard the long-term survival of the species.

PMID- 23132906
TI  - A phylogeographic study of the endemic rodent Eliurus carletoni (Rodentia:
      Nesomyinae) in an ecological transition zone of Northern Madagascar.
AB  - We conducted a mitochondrial phylogeographic study of the endemic dry forest
      rodent Eliurus carletoni (Rodentia: Nesomyinae) in an ecological transition zone
      of northern Madagascar (Loky-Manambato) and 2 surrounding regions (Ankarana and
      Analamerana). The main goal was to assess the evolutionary consequences on this
      taxon of the complex landscape features and Quaternary ecological vicissitudes.
      Three haplogroups were identified from the 215 specimens obtained from 15
      populations. High levels of genetic diversity and significant genetic
      differentiation among populations were observed. The different geographical
      subdivisions of the study area by regions, by river catchment zones, and the
      physical distance between populations are not correlated with genetic patterns.
      In contrast, population structure is mostly explained by the geographic
      distribution of the samples among existing forest blocks. E. carletoni
      experienced a genetic bottleneck between 18 750 and 7500 years BP, which
      correlates with periods when moister climates existed on the island. Overall, our
      data suggest that the complex genetic patterns of E. carletoni can be explained
      by Quaternary climatic vicissitudes that resulted in habitat fluctuations between
      dry and humid forests, as well as subsequent human-induced fragmentation of
      forest habitat.

PMID- 23132908
TI  - A forest butterfly in sahara desert oases: isolation does not matter.
AB  - Numerous studies addressing the impact of habitat fragmentation on genetic
      diversity have been performed. In this study, we analyze the effects of a
      seemingly nonpermeable matrix on the population structure of the forest-dwelling
      butterfly Pararge aegeria in geographically isolated oases at the northern margin
      of the Sahara desert using microsatellites, morphological characters, and species
      distribution modeling. Results from all analyses are mostly congruent and reveal
      1) a split between European and North African populations, 2) rather low
      divergence between populations from the eastern and western part of North Africa
      (Morocco vs. Tunisia), 3) a lack of differentiation between the oasis and Atlas
      Mountain populations, 4) as well as among the oasis populations, and 5) no
      reduction of genetic variability in oasis populations. However, one exception to
      this general trend resulted from the analyses of wing shape; wings of butterflies
      from oases are more elongated compared with those from the other habitats. This
      pattern of phenotypic divergence may suggest a recent colonization of the oasis
      habitats by individuals, which might be accompanied by a rather dispersive
      behavior. Species distribution modeling suggests a fairly recent reexpansion of
      the species' climatic niche starting in the Holocene at about 6000 before
      present. The combined results indicate a rather recent colonization of the oases
      by highly mobile individuals from genetically diverse founder populations. The
      colonization was likely followed by the expansion and persistence of these
      founder populations under relatively stable environmental conditions. This,
      together with low rates of gene flow, likely prevented differentiation of
      populations via drift and led to the maintenance of high genetic diversity.

PMID- 23132909
TI  - ApoA-IV promotes the biogenesis of apoA-IV-containing HDL particles with the
      participation of ABCA1 and LCAT.
AB  - The objective of this study was to establish the role of apoA-IV, ABCA1, and LCAT
      in the biogenesis of apoA-IV-containing HDL (HDL-A-IV) using different mouse
      models. Adenovirus-mediated gene transfer of apoA-IV in apoA-I(-/-) mice did not
      change plasma lipid levels. ApoA-IV floated in the HDL2/HDL3 region, promoted the
      formation of spherical HDL particles as determined by electron microscopy, and
      generated mostly alpha- and a few pre-beta-like HDL subpopulations. Gene transfer
      of apoA-IV in apoA-I(-/-) * apoE(-/-) mice increased plasma cholesterol and
      triglyceride levels, and 80% of the protein was distributed in the VLDL/IDL/LDL
      region. This treatment likewise generated alpha- and pre-beta-like HDL
      subpopulations. Spherical and alpha-migrating HDL particles were not detectable
      following gene transfer of apoA-IV in ABCA1(-/-) or LCAT(-/-) mice. Coexpression
      of apoA-IV and LCAT in apoA-I(-/-) mice restored the formation of HDL-A-IV. Lipid
      free apoA-IV and reconstituted HDL-A-IV promoted ABCA1 and scavenger receptor BI
      (SR-BI)-mediated cholesterol efflux, respectively, as efficiently as apoA-I and
      apoE. Our findings are consistent with a novel function of apoA-IV in the
      biogenesis of discrete HDL-A-IV particles with the participation of ABCA1 and
      LCAT, and may explain previously reported anti-inflammatory and atheroprotective
      properties of apoA-IV.

PMID- 23132910
TI  - Functional genomic analysis of chromosomal aberrations in a compendium of 8000
      cancer genomes.
AB  - A large database of copy number profiles from cancer genomes can facilitate the
      identification of recurrent chromosomal alterations that often contain key cancer
      related genes. It can also be used to explore low-prevalence genomic events such
      as chromothripsis. In this study, we report an analysis of 8227 human cancer copy
      number profiles obtained from 107 array comparative genomic hybridization (CGH)
      studies. Our analysis reveals similarity of chromosomal arm-level alterations
      among developmentally related tumor types as well as a number of co-occurring
      pairs of arm-level alterations. Recurrent ("pan-lineage") focal alterations
      identified across diverse tumor types show an enrichment of known cancer-related
      genes and genes with relevant functions in cancer-associated phenotypes (e.g.,
      kinase and cell cycle). Tumor type-specific ("lineage-restricted") alterations
      and their enriched functional categories were also identified. Furthermore, we
      developed an algorithm for detecting regions in which the copy number oscillates
      rapidly between fixed levels, indicative of chromothripsis. We observed these
      massive genomic rearrangements in 1%-2% of the samples with variable tumor type
      specific incidence rates. Taken together, our comprehensive view of copy number
      alterations provides a framework for understanding the functional significance of
      various genomic alterations in cancer genomes.

PMID- 23132911
TI  - Genome-scale coestimation of species and gene trees.
AB  - Comparisons of gene trees and species trees are key to understanding major
      processes of genome evolution such as gene duplication and loss. Because current
      methods to reconstruct phylogenies fail to model the two-way dependency between
      gene trees and the species tree, they often misrepresent gene and species
      histories. We present a new probabilistic model to jointly infer rooted species
      and gene trees for dozens of genomes and thousands of gene families. We use
      simulations to show that this method accurately infers the species tree and gene
      trees, is robust to misspecification of the models of sequence and gene family
      evolution, and provides a precise historic record of gene duplications and losses
      throughout genome evolution. We simultaneously reconstruct the history of
      mammalian species and their genes based on 36 completely sequenced genomes, and
      use the reconstructed gene trees to infer the gene content and organization of
      ancestral mammalian genomes. We show that our method yields a more accurate
      picture of ancestral genomes than the trees available in the authoritative
      database Ensembl.

PMID- 23132913
TI  - A SULT2A1 genetic variant identified by GWAS as associated with low serum DHEAS
      does not impact on the actual DHEA/DHEAS ratio.
AB  - DHEA is the major precursor of human sex steroid synthesis and is inactivated via
      sulfonation to DHEAS. A previous genome-wide association study related the single
      nucleotide polymorphism (SNP) rs2637125, located near the coding region of DHEA
      sulfotransferase, SULT2A1, to serum DHEAS concentrations. However, the functional
      relevance of this SNP with regard to DHEA sulfonation is unknown. Using data from
      3300 participants of the population-based cohort Study of Health in Pomerania, we
      identified 43 individuals being homozygote for the minor allele of the SNP
      rs2637125 (AA) and selected two sex- and age-matched individuals with AG and GG
      genotype (n=172) respectively. Steroid analysis including measurement of serum
      DHEA and DHEAS was carried out by liquid chromatography/mass spectrometry,
      employing steroid oxime analysis for enhancing the sensitivity of DHEA detection.
      We applied quantile regression models to compare median hormone levels across
      SULT2A1 genotypes. Median comparisons by SULT2A1 genotype (AA vs AG and GG
      genotypes respectively) showed no differences in the considered hormones
      including DHEAS, DHEA, androstenedione, as well as cortisol and cortisone
      concentrations. SULT2A1 genotype also had no effect on the DHEA/DHEAS ratio. Sex
      stratified analyses, as well as alternative use of the SULT2A1 SNP rs182420,
      yielded similar negative results. Genetic variants of SULT2A1 do not appear to
      have an effect on individual DHEA and DHEAS concentrations or the DHEA/DHEAS
      ratio as a marker of DHEA sulfonation capacity.

PMID- 23132912
TI  - Targeted gene silencing in mouse germ cells by insertion of a homologous DNA into
      a piRNA generating locus.
AB  - In germ cells, early embryos, and stem cells of animals, PIWI-interacting RNAs
      (piRNAs) have an important role in silencing retrotransposons, which are vicious
      genomic parasites, through transcriptional and post-transcriptional mechanisms.
      To examine whether the piRNA pathway can be used to silence genes of interest in
      germ cells, we have generated knock-in mice in which a foreign DNA fragment was
      inserted into a region generating pachytene piRNAs. The knock-in sequence was
      transcribed, and the resulting RNA was processed to yield piRNAs in postnatal
      testes. When reporter genes possessing a sequence complementary to portions of
      the knock-in sequence were introduced, they were greatly repressed after the time
      of pachytene piRNA generation. This repression mainly occurred at the post
      transcriptional level, as degradation of the reporter RNAs was accelerated. Our
      results show that the piRNA pathway can be used as a tool for sequence-specific
      gene silencing in germ cells and support the idea that the piRNA generating
      regions serve as traps for retrotransposons, enabling the host cell to generate
      piRNAs against active retrotransposons.

PMID- 23132914
TI  - Structurally similar estradiol analogs uniquely alter the regulation of
      intracellular signaling pathways.
AB  - Ligand structure can affect the activation of nuclear receptors, such as estrogen
      receptors (ERs), and their control of signaling pathways for cellular responses
      including death and differentiation. We hypothesized that distinct biological
      functions of similar estradiol (E(2)) analogs could be identified by integrating
      gene expression patterns obtained from human tumor cell lines with receptor
      binding and functional data for the purpose of developing compounds for treatment
      of a variety of diseases. We compared the estrogen receptor subtype selectivity
      and impact on signaling pathways for three distinct, but structurally similar,
      analogs of E(2). Modifications in the core structure of E(2) led to pronounced
      changes in subtype selectivity for estrogen receptors, ER-alpha or ER-beta, along
      with varying degrees of ER dimerization and activation. While all three E(2)
      analogs are predominantly ER-beta agonists, the cell growth inhibitory activity
      commonly associated with this class of compounds was detected for only two of the
      analogs and might be explained by a ligand-specific pattern of gene
      transcription. Microarray studies using three different human tumor cell lines
      demonstrated that the analogs distinctly affect the transcription of genes in
      signaling pathways for chromosome replication, cell death, and oligodendrocyte
      progenitor cell differentiation. That the E(2) analogs could lower tumor cell
      viability and stimulate neuronal differentiation confirmed that gene expression
      data could accurately distinguish biological activity of the E(2) analogs. The
      findings reported here confirm that cellular responses can be regulated by making
      key structural alterations to the core structure of endogenous ER ligands.

PMID- 23132916
TI  - Community participation of cross-border migrants for primary health care in
      Thailand.
AB  - This is the first report of the large-scale utilization of migrants as health
      volunteers in a migrant primary-healthcare program. The program recruited
      migrants who volunteered to serve their communities. This study explores the
      identities of these volunteers, their relationship with program management, and
      their attitudes. The study also investigates the impact of the volunteers, from
      the migrants' and healthcare workers' perspective. The study was conducted in two
      provinces, Tak (northern Thailand) and Samut Sakhon (central Thailand). Primary
      and secondary information was collected. Mixed methods, comprising in-depth
      interviews, observation and questionnaires, were used to gather primary data from
      three groups of participants-migrant volunteers, migrants and healthcare workers.
      Secondary data, and in-depth interviews with healthcare workers, showed that
      migrant volunteers made a significant contribution to the provision of both
      preventive and curative services. The quantitative study covered 260 migrant
      volunteers and 446 migrants. The results found that <5% of volunteers were
      selected by the community. Almost all attended a training course. Most were
      assigned to be health communicators; four stated they did nothing. Volunteers'
      attitudes were very positive. Most migrants reported that the volunteers' work
      was useful. It was concluded that the migrant health-volunteer program did help
      deal with migrant health problems. However, management of the program should be
      closely considered for more effective outcomes. 

PMID- 23132917
TI  - Mortality rates or sociomedical indicators? The work of the League of Nations on
      standardizing the effects of the Great Depression on health.
AB  - This article explores the first international effort by the League of Nations
      Health Organization (LNHO) to standardize the study of the effects of the
      economic crisis of the 1930s on health. Instead of analysing this effort with the
      benefit of hindsight, this article takes into account the actors' perspectives
      and, therefore, it relies on the documents produced by the LNHO and public health
      experts of the 1930s, as well as on the historical scholarship on this subject.
      This article shows that, despite the declining death rates in Europe and in the
      US during the crisis, the LNHO considered that death rates concealed a more
      subtle effect of the crisis on health; hence, they launched a project aimed at
      making the effect visible. It describes the LNHO programme and the guidelines and
      methods set out by the organization in 1932 to observe this subtle effect through
      sociomedical investigations. The results of these surveys are summarized and the
      article discusses how the eugenic arguments used to explain them were not
      accepted by the LNHO. The article also shows how some members of the LNHO
      considered the results of the sociomedical surveys inconclusive and questioned
      the usefulness of socioeconomic indicators; in so doing, they raised concerns
      about the intervention of the LNHO in national matters and about the risks of
      crossing the established limits between science and politics. This article shows
      that an historical analysis, which takes into account the points of view of the
      actors involved, illuminates the factors that led the LNHO to conclude that
      mortality rates were the best method for measuring the effects of the economic
      crisis on health and that, as they were declining, the Great Depression was not
      having any deleterious effect on public health. 

PMID- 23132915
TI  - Parity and institutional delivery in rural Tanzania: a multilevel analysis and
      policy implications.
AB  - OBJECTIVES: We assess the extent to which the use of healthcare facilities for
      childbirth varies by parity, conditional on socio-economic, psychological and
      health characteristics. We also assess differences in the determinants of
      institutionalized delivery for first-time mothers and multiparous, and explore
      village-level variations in observed relationships. METHODS: Survey data from a
      three-stage cross-sectional cluster sample of 1205 women from a rural district of
      Tanzania were analysed using random-intercept multilevel models. RESULTS: Use of
      health facilities for delivery was low (39%), with odds of institutionalized
      delivery three times higher among nulliparous women (0 children prior to current
      delivery) compared with women with one to four children; and 30% lower among
      women with five or more children compared with those with one to four children.
      In parity group analyses, women with at least some education and women with more
      than three antenatal care visits had higher odds of institutionalized delivery
      among nulliparous. Belief in the importance of institutionalized delivery
      increased the odds of delivering in a facility among multiparous women; so did
      health insurance for women with five or more children. We found a significant
      variation in institutionalized delivery among multiparous women based on their
      village of residence (one to four and five or more children), but these
      variations were not observed among nulliparous women. CONCLUSION: Parity is a
      pivotal determinant of the use of health facilities for delivery, and its
      significance varies by village of residence; hence, interventions targeting women
      according to parity may increase the use of facilities for delivery in rural
      Tanzania. Future research should focus on the village-level characteristics that
      influence institutionalized delivery in multiparous.

PMID- 23132922
TI  - Re: Effect of ADAM28 on carcinoma cell metastasis by cleavage of von Willebrand
      factor.

PMID- 23132923
TI  - Regulation of directional cell migration by membrane-induced actin bundling.
AB  - During embryonic development and in metastatic cancers, cells detach from the
      epithelium and migrate with persistent directionality. Directional cell migration
      is also crucial for the regeneration and maintenance of the epithelium and
      impaired directional migration is linked to chronic inflammatory diseases.
      Despite its significance, the mechanisms controlling epithelial cell migration
      remain poorly understood. Villin is an epithelial-cell-specific actin modifying
      protein that regulates epithelial cell plasticity and motility. In motile cells
      villin is associated with the highly branched and the unbranched actin filaments
      of lamellipodia and filopodia, respectively. In this study we demonstrate for the
      first time that villin regulates directionally persistent epithelial cell
      migration. Functional characterization of wild-type and mutant villin proteins
      revealed that the ability of villin to self-associate and bundle actin as well as
      its direct interaction with phosphatidylinositol 4,5-bisphosphate
      [PtdIns(4,5)P(2)] regulates villin-induced filopodial assembly and directional
      cell migration. Our findings suggest that convergence of different signaling
      cascades could spatially restrict villin activity to areas of high
      PtdIns(4,5)P(2) and F-actin concentration to assemble filopodia. Furthermore, our
      data reveal the ability of villin to undergo actin- and PtdIns(4,5)P(2)-induced
      self-association, which may be particularly suited to coalesce and reorganize
      actin bundles within the filopodia.

PMID- 23132924
TI  - Microsomal triacylglycerol transfer protein (MTP) is required to expand tracheal
      lumen in Drosophila in a cell-autonomous manner.
AB  - The Drosophila tracheal system is a useful model for dissecting the molecular
      mechanisms controlling the assembly and expansion of tubular organs. We have
      identified microsomal triacylglycerol transfer protein (MTP) as a new player
      involved in the lumen expansion in unicellular tubes. MTP is an endoplasmic
      reticulum resident protein that can transfer triglycerides and phospholipids
      between membranes in vitro. MTP lipid transfer activity is crucial for the
      assembly and secretion of apoB family lipoproteins, which are carriers of lipids
      between different tissues. Here we describe an unexpected role of MTP in tracheal
      development, which we postulate to be independent of its known function in
      lipoprotein secretion. We propose that, in tracheal cells, MTP is involved in
      regulation of de novo apical membrane delivery to the existing lumen and thus
      promotes proper expansion of the larval tracheal system.

PMID- 23132926
TI  - Glutathione peroxidase 3, a new retinoid target gene, is crucial for human
      skeletal muscle precursor cell survival.
AB  - Protection of satellite cells from cytotoxic damages is crucial to ensure
      efficient adult skeletal muscle regeneration and to improve therapeutic efficacy
      of cell transplantation in degenerative skeletal muscle diseases. It is therefore
      important to identify and characterize molecules and their target genes that
      control the viability of muscle stem cells. Recently, we demonstrated that high
      aldehyde dehydrogenase activity is associated with increased viability of human
      myoblasts. In addition to its detoxifying activity, aldehyde dehydrogenase can
      also catalyze the irreversible oxidation of vitamin A to retinoic acid;
      therefore, we examined whether retinoic acid is important for myoblast viability.
      We showed that when exposed to oxidative stress induced by hydrogen peroxide,
      adherent human myoblasts entered apoptosis and lost their capacity for adhesion.
      Pre-treatment with retinoic acid reduced the cytotoxic damage ex vivo and
      enhanced myoblast survival in transplantation assays. The effects of retinoic
      acid were maintained in dystrophic myoblasts derived from facioscapulohumeral
      patients. RT-qPCR analysis of antioxidant gene expression revealed glutathione
      peroxidase 3 (Gpx3), a gene encoding an antioxidant enzyme, as a potential
      retinoic acid target gene in human myoblasts. Knockdown of Gpx3 using short
      interfering RNA induced elevation in reactive oxygen species and cell death. The
      anti-cytotoxic effects of retinoic acid were impaired in GPx3-inactivated
      myoblasts, which indicates that GPx3 regulates the antioxidative effects of
      retinoic acid. Therefore, retinoid status and GPx3 levels may have important
      implications for the viability of human muscle stem cells.

PMID- 23132925
TI  - LDL receptor-related protein-1 is a sialic-acid-independent receptor for myelin
      associated glycoprotein that functions in neurite outgrowth inhibition by MAG and
      CNS myelin.
AB  - In the injured adult mammalian central nervous system (CNS), products are
      generated that inhibit neuronal sprouting and regeneration. In recent years, most
      attention has focused on the myelin-associated inhibitory proteins (MAIs) Nogo-A,
      OMgp, and myelin-associated glycoprotein (MAG). Binding of MAIs to neuronal cell
      surface receptors leads to activation of RhoA, growth cone collapse, and neurite
      outgrowth inhibition. In the present study, we identify low-density lipoprotein
      (LDL) receptor-related protein-1 (LRP1) as a high-affinity, endocytic receptor
      for MAG. In contrast with previously identified MAG receptors, binding of MAG to
      LRP1 occurs independently of terminal sialic acids. In primary neurons,
      functional inactivation of LRP1 with receptor-associated protein, depletion by
      RNA interference (RNAi) knock-down, or LRP1 gene deletion is sufficient to
      significantly reverse MAG and myelin-mediated inhibition of neurite outgrowth.
      Similar results are observed when LRP1 is antagonized in PC12 and N2a cells. By
      contrast, inhibiting LRP1 does not attenuate inhibition of neurite outgrowth
      caused by chondroitin sulfate proteoglycans. Mechanistic studies in N2a cells
      showed that LRP1 and p75NTR associate in a MAG-dependent manner and that MAG
      mediated activation of RhoA may involve both LRP1 and p75NTR. LRP1 derivatives
      that include the complement-like repeat clusters CII and CIV bind MAG and other
      MAIs. When CII and CIV were expressed as Fc-fusion proteins, these proteins,
      purified full-length LRP1 and shed LRP1 all attenuated the inhibition of neurite
      outgrowth caused by MAG and CNS myelin in primary neurons. Collectively, our
      studies identify LRP1 as a novel MAG receptor that functions in neurite outgrowth
      inhibition.

PMID- 23132927
TI  - Assembly of non-contractile dorsal stress fibers requires alpha-actinin-1 and
      Rac1 in migrating and spreading cells.
AB  - Cell migration and spreading is driven by actin polymerization and actin stress
      fibers. Actin stress fibers are considered to contain alpha-actinin crosslinkers
      and nonmuscle myosin II motors. Although several actin stress fiber subtypes have
      been identified in migrating and spreading cells, the degree of molecular
      diversity of their composition and the signaling pathways regulating fiber
      subtypes remain largely uncharacterized. In the present study we identify that
      dorsal stress fiber assembly requires alpha-actinin-1. Loss of dorsal stress
      fibers in alpha-actinin-1-depleted cells results in defective maturation of
      leading edge focal adhesions. This is accompanied by a delay in early cell
      spreading and slower cell migration without noticeable alterations in myosin
      light chain phosphorylation. In agreement with the unaltered myosin II activity,
      dorsal stress fiber trunks lack myosin II and are resistant to myosin II ATPase
      inhibition. Furthermore, the non-contractility of dorsal stress fibers is
      supported by the finding that Rac1 induces dorsal stress fiber assembly whereas
      contractile ventral stress fibers are induced by RhoA. Loss of dorsal stress
      fibers either by depleting alpha-actinin-1 or Rac1 results in a beta-actin
      accumulation at the leading edge in migrating and spreading cells. These findings
      molecularly specify dorsal stress fibers from other actin stress fiber subtypes.
      Furthermore, we propose that non-contractile dorsal stress fibers promote cell
      migration and early cell spreading through Rac1-induced actin polymerization.

PMID- 23132928
TI  - Delineating the core regulatory elements crucial for directed cell migration by
      examining folic-acid-mediated responses.
AB  - Dictyostelium discoideum shows chemotaxis towards folic acid (FA) throughout
      vegetative growth, and towards cAMP during development. We determined the
      spatiotemporal localization of cytoskeletal and signaling molecules and
      investigated the FA-mediated responses in a number of signaling mutants to
      further our understanding of the core regulatory elements that are crucial for
      cell migration. Proteins enriched in the pseudopods during chemotaxis also
      relocalize transiently to the plasma membrane during uniform FA stimulation. In
      contrast, proteins that are absent from the pseudopods during migration
      redistribute transiently from the PM to the cytosol when cells are globally
      stimulated with FA. These chemotactic responses to FA were also examined in cells
      lacking the GTPases Ras C and G. Although Ras and phosphoinositide 3-kinase
      activity were significantly decreased in Ras G and Ras C/G nulls, these mutants
      still migrated towards FA, indicating that other pathways must support FA
      mediated chemotaxis. We also examined the spatial movements of PTEN in response
      to uniform FA and cAMP stimulation in phospholipase C (PLC) null cells. The lack
      of PLC strongly influences the localization of PTEN in response to FA, but not
      cAMP. In addition, we compared the gradient-sensing behavior of polarized cells
      migrating towards cAMP to that of unpolarized cells migrating towards FA. The
      majority of polarized cells make U-turns when the cAMP gradient is switched from
      the front of the cell to the rear. Conversely, unpolarized cells immediately
      extend pseudopods towards the new FA source. We also observed that plasma
      membrane phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3] levels
      oscillate in unpolarized cells treated with Latrunculin-A, whereas polarized
      cells had stable plasma membrane PtdIns(3,4,5)P3 responses toward the
      chemoattractant gradient source. Results were similar for cells that were starved
      for 4 hours, with a mixture of polarized and unpolarized cells responding to
      cAMP. Taken together, these findings suggest that similar components control
      gradient sensing during FA- and cAMP-mediated motility, but the response of
      polarized cells is more stable, which ultimately helps maintain their
      directionality.

PMID- 23132930
TI  - The where, when and how of microtubule nucleation - one ring to rule them all.
AB  - The function of microtubules depends on their arrangement into highly ordered
      arrays. Spatio-temporal control over the formation of new microtubules and
      regulation of their properties are central to the organization of these arrays.
      The nucleation of new microtubules requires gamma-tubulin, an essential protein
      that assembles into multi-subunit complexes and is found in all eukaryotic
      organisms. However, the way in which gamma-tubulin complexes are regulated and
      how this affects nucleation and, potentially, microtubule behavior, is poorly
      understood. gamma-tubulin has been found in complexes of various sizes but
      several lines of evidence suggest that only large, ring-shaped complexes function
      as efficient microtubule nucleators. Human gamma-tubulin ring complexes
      (gammaTuRCs) are composed of gamma-tubulin and the gamma-tubulin complex
      components (GCPs) 2, 3, 4, 5 and 6, which are members of a conserved protein
      family. Recent work has identified additional unrelated gammaTuRC subunits, as
      well as a large number of more transient gammaTuRC interactors. In this
      Commentary, we discuss the regulation of gammaTuRC-dependent microtubule
      nucleation as a key mechanism of microtubule organization. Specifically, we focus
      on the regulatory roles of the gammaTuRC subunits and interactors and present an
      overview of other mechanisms that regulate gammaTuRC-dependent microtubule
      nucleation and organization.

PMID- 23132929
TI  - Cell cycle regulation by the NEK family of protein kinases.
AB  - Genetic screens for cell division cycle mutants in the filamentous fungus
      Aspergillus nidulans led to the discovery of never-in-mitosis A (NIMA), a
      serine/threonine kinase that is required for mitotic entry. Since that discovery,
      NIMA-related kinases, or NEKs, have been identified in most eukaryotes, including
      humans where eleven genetically distinct proteins named NEK1 to NEK11 are
      expressed. Although there is no evidence that human NEKs are essential for
      mitotic entry, it is clear that several NEK family members have important roles
      in cell cycle control. In particular, NEK2, NEK6, NEK7 and NEK9 contribute to the
      establishment of the microtubule-based mitotic spindle, whereas NEK1, NEK10 and
      NEK11 have been implicated in the DNA damage response. Roles for NEKs in other
      aspects of mitotic progression, such as chromatin condensation, nuclear envelope
      breakdown, spindle assembly checkpoint signalling and cytokinesis have also been
      proposed. Interestingly, NEK1 and NEK8 also function within cilia, the
      microtubule-based structures that are nucleated from basal bodies. This has led
      to the current hypothesis that NEKs have evolved to coordinate microtubule
      dependent processes in both dividing and non-dividing cells. Here, we review the
      functions of the human NEKs, with particular emphasis on those family members
      that are involved in cell cycle control, and consider their potential as
      therapeutic targets in cancer.

PMID- 23132931
TI  - Keratin 1 maintains skin integrity and participates in an inflammatory network in
      skin through interleukin-18.
AB  - Keratin 1 (KRT1) and its heterodimer partner keratin 10 (KRT10) are major
      constituents of the intermediate filament cytoskeleton in suprabasal epidermis.
      KRT1 mutations cause epidermolytic ichthyosis in humans, characterized by loss of
      barrier integrity and recurrent erythema. In search of the largely unknown
      pathomechanisms and the role of keratins in barrier formation and inflammation
      control, we show here that Krt1 is crucial for maintenance of skin integrity and
      participates in an inflammatory network in murine keratinocytes. Absence of Krt1
      caused a prenatal increase in interleukin-18 (IL-18) and the S100A8 and S100A9
      proteins, accompanied by a barrier defect and perinatal lethality. Depletion of
      IL-18 partially rescued Krt1(-/-) mice. IL-18 release was keratinocyte
      autonomous, KRT1 and caspase-1 dependent, supporting an upstream role of KRT1 in
      the pathology. Finally, transcriptome profiling revealed a Krt1-mediated gene
      expression signature similar to atopic eczema and psoriasis, but different from
      Krt5 deficiency and epidermolysis bullosa simplex. Our data suggest a functional
      link between KRT1 and human inflammatory skin diseases.

PMID- 23132932
TI  - Men's judgments of women's facial attractiveness from two- and three-dimensional
      images are similar.
AB  - Although most research on human facial attractiveness has used front-facing two
      dimensional (2D) images, our primary visual experience with faces is in three
      dimensions. Because face coding in the human visual system is viewpoint-specific,
      faces may be processed differently from different angles. Thus, results from
      perceptual studies using front-facing 2D facial images may not be generalizable
      to other viewpoints. We used rotating three-dimensional (3D) images of women's
      faces to test whether men's attractiveness ratings of women's faces from 2D and
      3D images differed. We found a significant positive correlation between men's
      judgments of women's facial attractiveness from 2D and 3D images (r = 0.707),
      suggesting that attractiveness judgments from 2D images are valid and provide
      similar information about women's attractiveness as do 3D images. We also found
      that women's faces were rated significantly more attractive in 3D images than in
      2D images. Our study verifies a novel method using 3D facial images, which may be
      important for future research on viewpoint-specific social perception. This
      method may also be valuable for the accurate measurement and assessment of facial
      characteristics such as averageness, identity, attractiveness, and emotional
      expression.

PMID- 23132933
TI  - Internalizing symptoms and functional disability in children with noncardiac
      chest pain and innocent heart murmurs.
AB  - OBJECTIVE: To examine the occurrence of internalizing symptoms and functional
      disability in children with noncardiac chest pain (NCCP) compared with children
      with innocent heart murmurs (IHMs). METHOD: 67 children with NCCP (M [SD] age =
      12.61 [2.63]; 68.7% Caucasian) and 62 children with IHM (M [SD] age = 12.67
      [2.62]; 50% Caucasian) were recruited from pediatric cardiology offices. Children
      and parents completed measures of psychological functioning and functional
      disability during a first visit to the cardiologist before diagnosis. RESULTS:
      Children with NCCP reported greater levels of anxiety, depression, and anxiety
      sensitivity than children with IHM. Children with NCCP and their parents reported
      greater levels of functional disability and somatization than children with IHM
      and their parents. CONCLUSION: Children with NCCP experience greater levels of
      psychosocial distress and impairment than similarly physically healthy children
      with IHM. Consideration of psychosocial influences on NCCP would likely be
      beneficial in aiding assessment and treatment.

PMID- 23132934
TI  - Longitudinal invariance of measurement and structure of global self-concept: a
      population-based study examining trajectories among adolescents with and without
      chronic illness.
AB  - OBJECTIVE: The objectives of this study were to determine whether a measure of
      global self-concept demonstrated longitudinal measurement invariance between
      adolescents aged 10-19 years with and without chronic illness and to document
      differences in their global self-concept trajectories over time. METHODS: Data
      were obtained from the National Longitudinal Survey of Children and Youth (N =
      10,064). Global self-concept was measured using a scale based on the Self
      Determination Questionnaire. RESULTS: 16 percent of adolescents had chronic
      illness. There was evidence of partial longitudinal invariance in global self
      concept between adolescents with and without chronic illness. Controlling for
      sociodemographic characteristics, adolescents with a chronic illness exhibited
      lower levels of global self-concept and more precipitous declines over time.
      CONCLUSIONS: The results from this study suggest that comparisons of global self
      concept between adolescents with and without chronic illness are meaningful and,
      compared to healthy controls, adolescents with chronic illness are at risk for
      low global self-concept.

PMID- 23132935
TI  - High levels of reflectivity and pointillist structural color in fish,
      cephalopods, and beetles.

PMID- 23132936
TI  - Vitamin D and tuberculosis.

PMID- 23132937
TI  - RNA-seq pinpoints a Xanthomonas TAL-effector activated resistance gene in a large
      crop genome.
AB  - Transcription activator-like effector (TALE) proteins of the plant pathogenic
      bacterial genus Xanthomonas bind to and transcriptionally activate host
      susceptibility genes, promoting disease. Plant immune systems have taken
      advantage of this mechanism by evolving TALE binding sites upstream of resistance
      (R) genes. For example, the pepper Bs3 and rice Xa27 genes are hypersensitive
      reaction plant R genes that are transcriptionally activated by corresponding
      TALEs. Both R genes have a hallmark expression pattern in which their transcripts
      are detectable only in the presence and not the absence of the corresponding
      TALE. By transcriptome profiling using next-generation sequencing (RNA-seq), we
      tested whether we could avoid laborious positional cloning for the isolation of
      TALE-induced R genes. In a proof-of-principle experiment, RNA-seq was used to
      identify a candidate for Bs4C, an R gene from pepper that mediates recognition of
      the Xanthomonas TALE protein AvrBs4. We identified one major Bs4C candidate
      transcript by RNA-seq that was expressed exclusively in the presence of AvrBs4.
      Complementation studies confirmed that the candidate corresponds to the Bs4C gene
      and that an AvrBs4 binding site in the Bs4C promoter directs its transcriptional
      activation. Comparison of Bs4C with a nonfunctional allele that is unable to
      recognize AvrBs4 revealed a 2-bp polymorphism within the TALE binding site of the
      Bs4C promoter. Bs4C encodes a structurally unique R protein and Bs4C-like genes
      that are present in many solanaceous genomes seem to be as tightly regulated as
      pepper Bs4C. These findings demonstrate that TALE-specific R genes can be cloned
      from large-genome crops with a highly efficient RNA-seq approach.

PMID- 23132939
TI  - Climate change and marine ecosystems.

PMID- 23132940
TI  - Fluctuation broadening in carbon nanotube resonators.
AB  - We simulated the behavior of suspended carbon nanotube resonators over a broad
      range of temperatures to explore the physics of semiflexible polymers in
      underdamped environments. We find that thermal fluctuations induce strong
      coupling between resonance modes. This effect leads to spectral fluctuations that
      readily account for the experimentally observed quality factors Q ~ 100 at 300 K.
      Using a mean-field approach to describe fluctuations, we analytically calculate Q
      and frequency shifts in tensioned and buckled carbon nanotubes and find excellent
      agreement with simulations.

PMID- 23132938
TI  - RNA polymerase III subunit architecture and implications for open promoter
      complex formation.
AB  - Transcription initiation by eukaryotic RNA polymerase (Pol) III relies on the
      TFIIE-related subcomplex C82/34/31. Here we combine cross-linking and hydroxyl
      radical probing to position the C82/34/31 subcomplex around the Pol III active
      center cleft. The extended winged helix (WH) domains 1 and 4 of C82 localize to
      the polymerase domains clamp head and clamp core, respectively, and the two WH
      domains of C34 span the polymerase cleft from the coiled-coil region of the clamp
      to the protrusion. The WH domains of C82 and C34 apparently cooperate with other
      mobile regions flanking the cleft during promoter DNA binding, opening, and
      loading. Together with published data, our results complete the subunit
      architecture of Pol III and indicate that all TFIIE-related components of
      eukaryotic and archaeal transcription systems adopt an evolutionarily conserved
      location in the upper part of the cleft that supports their functions in open
      promoter complex formation and stabilization.

PMID- 23132941
TI  - A classification of spin frustration in molecular magnets from a physical study
      of large odd-numbered-metal, odd electron rings.
AB  - The term "frustration" in the context of magnetism was originally used by P. W.
      Anderson and quickly adopted for application to the description of spin glasses
      and later to very special lattice types, such as the kagome. The original use of
      the term was to describe systems with competing antiferromagnetic interactions
      and is important in current condensed matter physics in areas such as the
      description of emergent magnetic monopoles in spin ice. Within molecular
      magnetism, at least two very different definitions of frustration are used. Here
      we report the synthesis and characterization of unusual nine-metal rings, using
      magnetic measurements and inelastic neutron scattering, supported by density
      functional theory calculations. These compounds show different
      electronic/magnetic structures caused by frustration, and the findings lead us to
      propose a classification for frustration within molecular magnets that
      encompasses and clarifies all previous definitions.

PMID- 23132942
TI  - Category-selective phase coding in the superior temporal sulcus.
AB  - Object perception and categorization can occur so rapidly that behavioral
      responses precede or co-occur with the firing rate changes in the object
      selective neocortex. Phase coding could, in principle, support rapid
      representation of object categories, whereby the first spikes evoked by a
      stimulus would appear at different phases of an oscillation, depending on the
      object category. To determine whether object-selective regions of the neo-cortex
      demonstrate phase coding, we presented images of faces and objects to two monkeys
      while recording local field potentials (LFP) and single unit activity from object
      selective regions in the upper bank superior temporal sulcus. Single units showed
      preferred phases of firing that depended on stimulus category, emerging with the
      initiation of spiking responses after stimulus onset. Differences in phase of
      firing were seen below 20 Hz and in the gamma and high-gamma frequency ranges.
      For all but the <20-Hz cluster, phase differences remained category-specific even
      when controlling for stimulus-locked activity, revealing that phase-specific
      firing is not a simple consequence of category-specific differences in the evoked
      responses of the LFP. In addition, we tested for firing rate-to-phase conversion.
      Category-specific differences in firing rates accounted for 30-40% of the
      explained variance in phase occurring at lower frequencies (<20 Hz) during the
      initial response, but was limited (<20% of the explained variance) in the 30- to
      60-Hz frequency range, suggesting that gamma phase-of-firing effects reflect more
      than evoked LFP and firing rate responses. The present results are consistent
      with theoretical models of rapid object processing and extend previous
      observations of phase coding to include object-selective neocortex.

PMID- 23132943
TI  - Watching a signaling protein function in real time via 100-ps time-resolved Laue
      crystallography.
AB  - To understand how signaling proteins function, it is crucial to know the time
      ordered sequence of events that lead to the signaling state. We recently
      developed on the BioCARS 14-IDB beamline at the Advanced Photon Source the
      infrastructure required to characterize structural changes in protein crystals
      with near-atomic spatial resolution and 150-ps time resolution, and have used
      this capability to track the reversible photocycle of photoactive yellow protein
      (PYP) following trans-to-cis photoisomerization of its p-coumaric acid (pCA)
      chromophore over 10 decades of time. The first of four major intermediates
      characterized in this study is highly contorted, with the pCA carbonyl rotated
      nearly 90 degrees  out of the plane of the phenolate. A hydrogen bond between the
      pCA carbonyl and the Cys69 backbone constrains the chromophore in this unusual
      twisted conformation. Density functional theory calculations confirm that this
      structure is chemically plausible and corresponds to a strained cis intermediate.
      This unique structure is short-lived (~600 ps), has not been observed in prior
      cryocrystallography experiments, and is the progenitor of intermediates
      characterized in previous nanosecond time-resolved Laue crystallography studies.
      The structural transitions unveiled during the PYP photocycle include trans/cis
      isomerization, the breaking and making of hydrogen bonds, formation/relaxation of
      strain, and gated water penetration into the interior of the protein. This
      mechanistically detailed, near-atomic resolution description of the complete PYP
      photocycle provides a framework for understanding signal transduction in
      proteins, and for assessing and validating theoretical/computational approaches
      in protein biophysics.

PMID- 23132945
TI  - STING manifests self DNA-dependent inflammatory disease.
AB  - Inflammatory autoimmune diseases such as systemic lupus erythematosus (SLE) and
      polyarthritis are characterized by chronic cytokine overproduction, suggesting
      that the stimulation of host innate immune responses, speculatively by persistent
      infection or self nucleic acids, plays a role in the manifestation of these
      disorders. Mice lacking DNase II die during embryonic development through
      comparable inflammatory disease because phagocytosed DNA from apoptotic cells
      cannot be adequately digested and intracellular host DNA sensor pathways are
      engaged, resulting in the production of a variety of cytokines including type I
      IFN. The cellular sensor pathway(s) responsible for triggering DNA-mediated
      inflammation aggravated autoimmune disease remains to be determined. However, we
      report here that Stimulator of IFN Genes (STING) is responsible for inflammation
      related embryonic death in DNase II defective mice initiated by self DNA. DNase
      II-dependent embryonic lethality was rescued by loss of STING function, and
      polyarthritis completely prevented because cytosolic DNA failed to robustly
      trigger cytokine production through STING-controlled signaling pathways. Our data
      provides significant molecular insight into the causes of DNA-mediated
      inflammatory disorders and affords a target that could plausibly be
      therapeutically controlled to help prevent such diseases.

PMID- 23132944
TI  - Neuronal code for extended time in the hippocampus.
AB  - The time when an event occurs can become part of autobiographical memories. In
      brain structures that support such memories, a neural code should exist that
      represents when or how long ago events occurred. Here we describe a neuronal
      coding mechanism in hippocampus that can be used to represent the recency of an
      experience over intervals of hours to days. When the same event is repeated after
      such time periods, the activity patterns of hippocampal CA1 cell populations
      progressively differ with increasing temporal distances. Coding for space and
      context is nonetheless preserved. Compared with CA1, the firing patterns of
      hippocampal CA3 cell populations are highly reproducible, irrespective of the
      time interval, and thus provide a stable memory code over time. Therefore, the
      neuronal activity patterns in CA1 but not CA3 include a code that can be used to
      distinguish between time intervals on an extended scale, consistent with
      behavioral studies showing that the CA1 area is selectively required for temporal
      coding over such periods.

PMID- 23132947
TI  - Counting primary loops in polymer gels.
AB  - Much of our fundamental knowledge related to polymer networks is built on an
      assumption of ideal end-linked network structure. Real networks invariably
      possess topological imperfections that negatively affect mechanical properties;
      modifications of classical network theories have been developed to account for
      these defects. Despite decades of effort, there are no known experimental
      protocols for precise quantification of even the simplest topological network
      imperfections: primary loops. Here we present a simple conceptual framework that
      enables primary loop quantification in polymeric materials. We apply this
      framework to measure the fraction of primary loop junctions in trifunctional PEG
      based hydrogels. We anticipate that the concepts described here will open new
      avenues of theoretical and experimental research related to polymer network
      structure.

PMID- 23132946
TI  - MiR-495 is a tumor-suppressor microRNA down-regulated in MLL-rearranged leukemia.
AB  - Acute myeloid leukemia (AML) is a heterogeneous group of hematopoietic
      malignancies with variable response to treatment. AMLs bearing MLL (mixed lineage
      leukemia) rearrangements are associated with intermediate or poor survival.
      MicroRNAs (miRNAs), a class of small noncoding RNAs, have been postulated to be
      important gene expression regulators virtually in all biological processes,
      including leukemogenesis. Through a large-scale, genome-wide miRNA expression
      profiling assay of 85 human AML and 15 normal control samples, we show that among
      48 miRNAs that are significantly differentially expressed between MLL- and non
      MLL-rearranged AML samples, only one (miR-495) is expressed at a lower level in
      MLL-rearranged AML than in non-MLL-rearranged AML; meanwhile, miR-495 is also
      significantly down-regulated in MLL-rearranged AML samples compared with normal
      control samples. Through in vitro colony-forming/replating assays and in vivo
      bone marrow transplantation studies, we show that forced expression of miR-495
      significantly inhibits MLL-fusion-mediated cell transformation in vitro and
      leukemogenesis in vivo. In human leukemic cells carrying MLL rearrangements,
      ectopic expression of miR-495 greatly inhibits cell viability and increases cell
      apoptosis. Furthermore, our studies demonstrate that PBX3 and MEIS1 are two
      direct target genes of miR-495, and forced expression of either of them can
      reverse the effects of miR-495 overexpression on inhibiting cell viability and
      promoting apoptosis of human MLL-rearranged leukemic cells. Thus, our data
      indicate that miR-495 likely functions as a tumor suppressor in AML with MLL
      rearrangements by targeting essential leukemia-related genes.

PMID- 23132948
TI  - Ion-beam irradiation, gene identification, and marker-assisted breeding in the
      development of low-cadmium rice.
AB  - Rice (Oryza sativa L.) grain is a major dietary source of cadmium (Cd), which is
      toxic to humans, but no practical technique exists to substantially reduce Cd
      contamination. Carbon ion-beam irradiation produced three rice mutants with <0.05
      mg Cd?kg(-1) in the grain compared with a mean of 1.73 mg Cd?kg(-1) in the
      parent, Koshihikari. We identified the gene responsible for reduced Cd uptake and
      developed a strategy for marker-assisted selection of low-Cd cultivars. Sequence
      analysis revealed that these mutants have different mutations of the same gene
      (OsNRAMP5), which encodes a natural resistance-associated macrophage protein.
      Functional analysis revealed that the defective transporter protein encoded by
      the mutant osnramp5 greatly decreases Cd uptake by roots, resulting in decreased
      Cd in the straw and grain. In addition, we developed DNA markers to facilitate
      marker-assisted selection of cultivars carrying osnramp5. When grown in Cd
      contaminated paddy fields, the mutants have nearly undetectable Cd in their
      grains and exhibit no agriculturally or economically adverse traits. Because
      mutants produced by ion-beam radiation are not transgenic plants, they are likely
      to be accepted by consumers and thus represent a practical choice for rice
      production worldwide.

PMID- 23132951
TI  - Pulmonary artery catheter placement guided by echocardiography.

PMID- 23132949
TI  - Dereplicating nonribosomal peptides using an informatic search algorithm for
      natural products (iSNAP) discovery.
AB  - Nonribosomal peptides are highly sought after for their therapeutic applications.
      As with other natural products, dereplication of known compounds and focused
      discovery of new agents within this class are central concerns of modern natural
      product-based drug discovery. Development of a chemoinformatic library-based and
      informatic search strategy for natural products (iSNAP) has been constructed and
      applied to nonribosomal peptides and proved useful for true nontargeted
      dereplication across a spectrum of nonribosomal peptides and within natural
      product extracts.

PMID- 23132952
TI  - Subcutaneous emphysema and pneumomediastinum.

PMID- 23132950
TI  - CTR1 phosphorylates the central regulator EIN2 to control ethylene hormone
      signaling from the ER membrane to the nucleus in Arabidopsis.
AB  - The gaseous phytohormone ethylene C(2)H(4) mediates numerous aspects of growth
      and development. Genetic analysis has identified a number of critical elements in
      ethylene signaling, but how these elements interact biochemically to transduce
      the signal from the ethylene receptor complex at the endoplasmic reticulum (ER)
      membrane to transcription factors in the nucleus is unknown. To close this gap in
      our understanding of the ethylene signaling pathway, the challenge has been to
      identify the target of the CONSTITUTIVE TRIPLE RESPONSE1 (CTR1) Raf-like protein
      kinase, as well as the molecular events surrounding ETHYLENE-INSENSITIVE2 (EIN2),
      an ER membrane-localized Nramp homolog that positively regulates ethylene
      responses. Here we demonstrate that CTR1 interacts with and directly
      phosphorylates the cytosolic C-terminal domain of EIN2. Mutations that block the
      EIN2 phosphorylation sites result in constitutive nuclear localization of the
      EIN2 C terminus, concomitant with constitutive activation of ethylene responses
      in Arabidopsis. Our results suggest that phosphorylation of EIN2 by CTR1 prevents
      EIN2 from signaling in the absence of ethylene, whereas inhibition of CTR1 upon
      ethylene perception is a signal for cleavage and nuclear localization of the EIN2
      C terminus, allowing the ethylene signal to reach the downstream transcription
      factors. These findings significantly advance our understanding of the mechanisms
      underlying ethylene signal transduction.

PMID- 23132953
TI  - Is there a role for stress CMR in stable chest pain with >60% predicted risk of
      coronary artery disease?

PMID- 23132954
TI  - Contrasting beliefs about screening for mental disorders among UK military
      personnel returning from deployment to Afghanistan.
AB  - OBJECTIVE: The objective of the study was to elicit beliefs and experiences of
      the value of a screening programme for mental illness among UK military
      personnel. METHOD: Three months after returning from Afghanistan 21 army
      personnel participated in a qualitative study about mental health screening. One
      to-one interviews were conducted and recorded. Data-driven thematic analysis was
      used. Researchers identified master themes represented by extracts of text from
      the 21 complete transcripts. RESULTS: Participants made positive remarks on the
      advantages of screening. Noted barriers to seeking help included: unwillingness
      to receive advice, a wish to deal with any problems themselves and a belief that
      military personnel should be strong enough to cope with any difficulties.
      Participants believed that overcoming barriers to participating in screening and
      seeking help would be best achieved by making screening compulsory. CONCLUSIONS:
      Although respondents were positive about a screening programme for mental
      illness, the barriers to seeking help for mental illness appear deep rooted and
      reinforced by the value ascribed to hardiness.

PMID- 23132955
TI  - Nativity Differences in Mothers' Health Behaviors: A Cross-National and
      Longitudinal Lens.

PMID- 23132956
TI  - Chemorheology of phenylboronate-salicylhydroxamate crosslinked hydrogel networks
      with a sulfonated polymer backbone.
AB  - Hydrogel networks crosslinked with polymer-bound phenylboronic acid (PBA) and
      salicylhydroxamic acid (SHA) demonstrate pH-reversible gel behavior due to the pH
      dependent equilibrium of the crosslinking moieties that form the gel network.
      Furthermore, the pH at which gels behave dynamically can be controlled by use of
      a polyelectrolyte backbone. Here we report on the frequency-dependent
      chemorheological characterization of PBA-SHA crosslinked hydrogel networks with a
      sulfonated polymer backbone. Our results suggest that the anionic nature of the
      polymers allows reversible crosslinking at neutral pH that an otherwise neutral
      backboned PBA-SHA crosslinked network cannot, and that these charge-induced
      dynamics can be effectively screened by ions in solution. Moreover, moduli
      frequency data can effectively be reduced into a single master curve with a
      neutral-backboned PBA-SHA gel data set as the reference condition.

PMID- 23132957
TI  - Neither MICA Nor DEPDC5 Genetic Polymorphisms Correlate with Hepatocellular
      Carcinoma Recurrence following Hepatectomy.
AB  - Purpose. Genetic polymorphisms of MICA and DEPDC5 have been reported to correlate
      with progression to hepatocellular carcinoma (HCC) in chronic hepatitis C
      patients. However, correlation of these genetic variants with HCC recurrence
      following hepatectomy has not yet been clarified. Methods. Ninety-six consecutive
      HCC patients who underwent hepatectomy, including 64 patients who were hepatitis
      C virus (HCV) positive, were genotyped for MICA (rs2596542) and DEPDC5
      (rs1012068). Recurrence-free survival rates (RFS) were compared for each
      genotype. Results. Five-year HCC recurrence-free survival (RFS) rates following
      hepatectomy were 20.7% in MICA GG allele carriers, 38.7% in GA, and 20.8% in AA,
      respectively (P = 0.72). The five-year RFS rate was 23.8% in DEPDC5 TT allele
      carriers and 31.8% in TG/GG, respectively (P = 0.47). The survival rates in all
      (including HCV-negative) patients were also similar among each MICA and DEPDC5
      genotype following hepatectomy. Among HCV-positive patients carrying the DEPDC5
      TG/GG allele, low fibrosis stage (F0-2) occurred more often compared with TT
      carriers (P < 0.05). Conclusions. Neither MICA nor DEPDC5 genetic polymorphism
      correlates with HCC recurrence following hepatectomy. DEPDC5 minor genotype data
      suggest a high susceptibility for HCC development in livers, even those with low
      fibrosis stages.

PMID- 23132958
TI  - Inhibition of osteoclast generation: a novel function of the bone morphogenetic
      protein 7/osteogenic protein 1.
AB  - Monocytes have the potential to differentiate to either macrophages, dendritic
      cells, or to osteoclasts. The microenvironment, particularly cytokines, directs
      the monocyte differentiation. Receptors of NFkappaB (RANK) ligand, tumor necrosis
      factor (TNF) alpha, or interleukin- (IL-) 8 have be identified as inducers of
      osteoclastogenesis, whereas others, such as IL-10 or transforming growth factor
      (TGF)beta inhibit osteoclast generation or induce differentiation towards a
      dendritic cell type. We now describe that bone morphogenetic protein (BMP)
      7/osteogenic protein- (OP-) 1 inhibited the differentiation of human CD14+
      monocytes to osteoclasts. In the presence of BMP7/OP-1 the transcription factors
      c-Fos and NFATc1, though upregulated and translocated to the nucleus in response
      to either RANKL or IL-8, did not persist. In parallel, MafB, a transcription
      factor expressed by monocytes and required for differentiation to macrophages but
      inhibiting osteoclast generation, was preserved. Because both persistence of
      NFATc1 and downregulation of MafB are crucial for osteoclastogenesis, we conclude
      that BMP7/OP-1 inhibits the generation of osteoclasts by interfering with
      signalling pathways.

PMID- 23132960
TI  - Anti-inflammatory properties of sirtuin 6 in human umbilical vein endothelial
      cells.
AB  - A prominent feature of inflammatory diseases is endothelial dysfunction. Factors
      associated with endothelial dysfunction include proinflammatory cytokines,
      adhesion molecules, and matrix degrading enzymes. At the transcriptional level,
      they are regulated by the histone deacetylase sirtuin (SIRT) 1 via its actions on
      the proinflammatory transcription factor nuclear factor-kappaB (NF-kappaB). The
      role of SIRT6, also a histone deacetylase, in regulating inflammation in
      endothelial cells is not known. The aim of this study was to determine the effect
      of SIRT6 knockdown on inflammatory markers in human umbilical vein endothelial
      cells (HUVECs) in the presence of lipopolysaccharide (LPS). LPS decreased
      expression of SIRT6 in HUVECs. Knockdown of SIRT6 increased the expression of
      proinflammatory cytokines (IL-1beta, IL-6, IL-8), COX-prostaglandin system, ECM
      remodelling enzymes (MMP-2, MMP-9 and PAI-1), the adhesion molecule ICAM-1, and
      proangiogenic growth factors VEGF and FGF-2; cell migration; cell adhesion to
      leukocytes. Loss of SIRT6 increased the expression of NF-kappaB, whereas
      overexpression of SIRT6 was associated with decreased NF-kappaB transcriptional
      activity. Taken together, these results demonstrate that the loss of SIRT6 in
      endothelial cells is associated with upregulation of genes involved in
      inflammation, vascular remodelling, and angiogenesis. SIRT6 may be a potential
      pharmacological target for inflammatory vascular diseases.

PMID- 23132962
TI  - Change and challenge.

PMID- 23132959
TI  - Leptospira and inflammation.
AB  - Leptospirosis is an important zoonosis and has a worldwide impact on public
      health. This paper will discuss both the role of immunogenic and pathogenic
      molecules during leptospirosis infection and possible new targets for
      immunotherapy against leptospira components. Leptospira, possess a wide variety
      of mechanisms that allow them to evade the host immune system and cause
      infection. Many molecules contribute to the ability of Leptospira to adhere,
      invade, and colonize. The recent sequencing of the Leptospira genome has
      increased our knowledge about this pathogen. Although the virulence factors,
      molecular targets, mechanisms of inflammation, and signaling pathways triggered
      by leptospiral antigens have been studied, some questions are still unanswered.
      Toll-like receptors (TLRs) are the primary sensors of invading pathogens. TLRs
      recognize conserved microbial pattern molecules and activate signaling pathways
      that are pivotal to innate and adaptive immune responses. Recently, a new
      molecular target has emerged--the Na/K-ATPase--which may contribute to
      inflammatory and metabolic alteration in this syndrome. Na/K-ATPase is a target
      for specific fatty acids of host origin and for bacterial components such as the
      glycolipoprotein fraction (GLP) that may lead to inflammasome activation. We
      propose that in addition to TLRs, Na/K-ATPase may play a role in the innate
      response to leptospirosis infection.

PMID- 23132961
TI  - Localization and upregulation of the nasal histamine H1 receptor in perennial
      allergic rhinitis.
AB  - In the present study, we have investigated the expression of histamine H1
      receptor in human turbinates by RT-PCR, western blotting, and
      immunohistochemistry. Human turbinates were obtained by turbinectomy from 12
      patients with nasal obstruction refractory to medical therapy. RT-PCR analysis of
      total RNA extracted from human nasal turbinate, primary cultured human nasal
      epithelial cells, and nasal vascular endothelial cells demonstrated the
      expression of histamine H1 receptor mRNA. About 56 kDa band was detected in human
      turbinates by western blot analysis using anti-H1 receptor antibody. The
      expression level of H1 receptor protein was marked in patients with nasal allergy
      than in patients with nonallergic rhinitis. The immunohistochemical study
      revealed that epithelial cells and vascular endothelial cells showed intense
      immunoreactivity for histamine H1 receptor. In addition, the blood vessels in
      superficial area expressed higher level of H1 receptor immunoreactivity than that
      in deeper area in the nasal mucosa. These results may have an important clinical
      implication for understanding the role of histamine H1 receptor on upper airway
      diseases such as allergic rhinitis and nonallergic rhinitis.

PMID- 23132963
TI  - Significance of Her-2/neu protein over expression in Indian breast cancer
      patients.
AB  - BACKGROUND: Racial disparity in presentation and outcome of breast cancer is
      established but cause is unexplained. Many studies show various molecular markers
      for racial differences in the prognosis of breast cancer. There is scarcity of
      data on prognostic significance of HER-2/neu in Indian breast cancer. AIMS AND
      OBJECTIVE: To know incidence and prognostic significance of HER-2/neu expression
      in Indian patients. To correlate HER-2/neu Expression with other prognostic
      markers and ER/PR Receptor status. MATERIAL AND METHODS: 112 consecutive patients
      with breast cancer attending the Department of Surgical Oncology from March 1997
      to March 2000 were included in this study. The clinical data along with ER/PR
      status, follow up data and HER-2/neu expression examined by immuno-histochemical
      method was recorded. STATISTICAL ANALYSIS: Data was analyzed by univariate and
      multivariate analysis for all prognostic factors. Significance was calculated by
      using Chi square test and survival analysis by using Kaplan Meier survival curve.
      RESULTS: The median age of 112 patients was 46.56 (+/-9.55) years. HER-2/neu over
      expression was present in 46.37%. Significant correlation was found between HER
      2/neu over expression and lymph node status, grade of tumor and ER/PR receptor
      status. Median follow up period of 23 months. There was significant tumour free
      survival advantage (p < 0.01) and overall survival advantage (p < 0.001) in
      patients with HER-2/neu negative expression. CONCLUSION: HER-2/neu oncogene over
      expression is higher (46.37%) among Indian patients in comparison to 25-30% shown
      in most western literature. HER-2/neu oncogene over expression significantly
      correlates with grade, lymph node involvement, ER/PR status and also affects
      survival.

PMID- 23132964
TI  - Laparoscopic adrenalectomy - a review of initial 24 consecutive patients.
AB  - AIM: To analyze patient demographics, pathology, surgical procedure and outcome
      in initial 24 consecutive patients who underwent laparoscopic adrenalectomy in
      our department. METHODS: Twenty four patients underwent laparoscopic
      adrenalectomy between September 2000 and August 2005. There were 12 males and 12
      females with a mean age of 44.6 years (range 25-68 years). The indications for
      adrenalectomy were pheochromocytoma (13 patients), Cushing's syndrome (5
      patients), myelolipoma (2 patients), adrenal cyst (2 patients), aldosteronoma (1
      patient) and adrenal incidentaloma (1 patient). Nineteen of our patients with
      functioning adrenal tumours were prepared preoperatively for periods ranging up
      to 2 weeks by the endocrinologist. All laparoscopic adrenalectomies were
      performed via lateral transperitoneal approach using standard four-port
      technique. Patients with pheochromocytoma and Cushing's syndrome were monitored
      in the surgical intensive care unit during immediate postoperative period. The
      clinical and intraoperative characteristics, complications and outcomes of all
      patients were analyzed. RESULTS: The mean operative time for laparoscopic
      adrenalectomy was 136 minutes. Intraoperative hypertension occurred in 8
      patients. Intraoperative hypotension occurred in 2 patients. One patient required
      conversion due to dense adhesions and hemorrhage. Postoperative complications
      were seen in six patients - immediate postoperative hypotension (2 patients),
      features of steroid withdrawal (2 patients) and postoperative pyrexia (2
      patients). Five patients with pheochromocytoma required antihypertensive drugs in
      the postoperative period. There was no mortality in our series. CONCLUSIONS:
      Laparoscopic adrenalectomy is a safe operation that incorporates all the benefits
      of minimal access surgery and is associated with a satisfactory postoperative
      outcome. A careful preoperative preparation in functioning adrenal tumours aids
      in the faster recovery of these patients.

PMID- 23132965
TI  - Necrotizing fascitis: an epidemiologic study of 102 cases.
AB  - BACKGROUND: Necrotizing fascitis is a progressive, rapidly spreading,
      inflammatory infection located in deep fascia. It may cause necrosis of skin and
      subcutaneous tissues. Spreading of it may lead to shock, organ failure and even
      death. METHODS: In this study, we evaluated prevalence of variables including
      predisposing factors, clinical and paraclinical findings, distribution of tissue
      involvement and mortality rate in 102 patients of necrotizing fascitis at our
      Hospital between the years 1995 and 2005. RESULTS: Prevalence of this disease was
      higher in males than females with the rate of 2.6:1. Diabetes mellitus was the
      most common predisposing disease. Genital region was the most common site of
      involvement. Muscles were involved in 25.5% of cases. Nonspecific erythema was
      the main dermatological manifestation. The most common organism was Enterococcus
      faecalis and mortality rate was 10.8%. CONCLUSION: Necrotizing fascitis is an
      infectious disease with high mortality rate and frequently with non-specific skin
      and general manifestations. High suspicion while visiting primary signs and
      surgical debridement can be effective in decreasing the rate of morbidity and
      mortality.

PMID- 23132966
TI  - Frozen section and fine needle aspiration biopsy in thyroid surgery - needles and
      sections.
AB  - PURPOSE: To review our own experience with fine needle aspiration biopsy (FNAB)
      and frozen section (FS) in thyroid surgery and to assess the value of FNAB and FS
      in predicting malignancy in patient with thyroid disease. METHODS: The records of
      300 patients who underwent thyroid surgery between April 2001 and June 2006 were
      analyzed. RESULTS: Of the 153 patients who had preoperative FNABs performed, 8
      (5.22%) were reported as indeterminate, 100 (65.35%) were read as benign, and 3
      (1.96%) were read as malignant. Fourty two of the FNABs were inadequate for
      evaluation (27.45%). When occult papillary carcinomas were excluded, sensitivity,
      and accuracy rates for FNAB reached 100%. One hundred and ninety one patients had
      FSs performed. 184 (96.33%) of these were reported as benign, 4 (2.09%)were
      reported as malignant, 3 (1.57%) were deferred to permanent paraffin (PP)
      sections. When occult papillary carcinomas were excluded, sensitivity, and
      accuracy rates for FS were 42.85%, 43%, and 97.28% respectively. CONCLUSIONS: Our
      data supports the use of FNAB in the confirmation of malignancy and the need for
      operation. The routine use of FS is not warranted. Selective use of FS when FNAB
      is nondiagnostic or indeterminate may provide additional information. Both FNAB
      and FS fail to reveal occult carcinomas of thyroid.

PMID- 23132967
TI  - A rare case of incidentally diagnosed primary papillary carcinoma of thyroglossal
      duct cyst.
AB  - Thyroglossal duct cysts are the most common congenital abnormality of thyroid
      development. Seventy percent of thyroglossal duct cysts are diagnosed during
      childhood and 7% are diagnosed in adulthood. Less than 1% of these cases are
      malignant with most being papillary in nature. It is often diagnosed incidentally
      after surgical excision. Incidentally discovered, well-differentiated thyroid
      carcinoma of the thyroglossal duct, in the presence of a clinically and
      radiologically normal thyroid gland, can be managed adequately by the Sistrunk
      operation. We present a rare case of primary papillary carcinoma of thyroglossal
      duct cyst, with normal thyroid gland, in a 28-year-old female that was diagnosed
      incidentally on histopathological examination. A Sistrunk procedure was performed
      on the patient to remove the thyroglossal duct cyst and patient is doing well at
      regular follow up.

PMID- 23132968
TI  - Giant vesical calculus presenting with azotaemia and anuria.
AB  - Giant vesical calculus is a rare clinical entity in modern urological practice.
      Vesical calculi are usually secondary to bladder outlet obstruction. The usual
      clinical presentation is with recurrent urinary tract infection, haematuria or
      with retention of urine. We report an elderly male patient who presented with
      azotaemia and anuria as a result of bilateral obstructive uropathy due to a giant
      vesical calculus.

PMID- 23132969
TI  - Pheochromocytoma of urinary bladder - a case report.
AB  - Pheochromocytomas are catecholamine producing neuroendocrine tumours. Bladder
      involvement with pheochromocytoma is rare that usually presents with
      hypertension, hematuria and syncope often related to voiding. Clinical
      manifestation may be inconsistent and high index of suspicion is required for
      accurate diagnosis. We report a case, who presented with gross intermittent
      hematuria and mild elevation of pulserate and bloodpressure. Patient was
      adequately treated with partial cystectomy.

PMID- 23132970
TI  - Retroperitoneal Castleman's disease mimicking soft tissue tumour.
AB  - Castleman's disease is a type of non-neoplastic lymphoproliferative disease
      having lymph nodal hyperplasia. It has two distinct microscopic types: hyaline
      vascular type and plasma cell type. Clinically, it may present either as a
      solitary mass, most commonly in the mediastinum, or as a multicentric form whose
      features are generalized lymph-adenopathy, splenomegaly and involvement of other
      organs like the lungs and kidneys. Here we report a case of isolated
      retroperitoneal Castleman's disease, which presented as a lump in the iliac fossa
      in a young female. A clinico-radio-logical diagnosis of retroperitoneal soft
      tissue tumour was made and the patient underwent complete surgical excision. The
      exact diagnosis was only obtained at histopathology and there is no evidence of
      recurrence at six months follow-up.

PMID- 23132971
TI  - 27 cm fetus in fetu presenting in a 36-year-old man: report of a rare case and
      brief review of literature.

PMID- 23132972
TI  - Klippel-trenaunay syndrome.

PMID- 23132973
TI  - Oncoplastic surgery for retro areolar breast cancer - a technical modification of
      the Grisotti flap.

PMID- 23132974
TI  - An ode to my alma mater - Madras Medical College.

PMID- 23132975
TI  - A tribute to Hugh Hampton Young - the father of modern urology.

PMID- 23132976
TI  - Live surgery telecast - surgery teaching tool or sensationalism?

PMID- 23132977
TI  - Proposed model of case based learning for training undergraduate medical student
      in surgery.
AB  - BACKGROUND: Systematic surveys of undergraduate medical education have cautiously
      supported the outcomes of Problem Based Learning (PBL) compared with traditional
      learning. This article provides a critical overview of PBL, its limitations in
      the developing country scenario and our proposed model of PBL triggered by Real
      cases, to address these limitations. AIM: Our hypothesis was to see whether the
      proposed CBL model would work in Indian set up in comparison with traditional
      teaching METHODS: We followed a modified Barrow's Model. A tutor selected a real
      case and created a problem scenario which was progressively disclosed to
      students, and learning issues were raised. In session 2 students presented self
      studied learning issues. The process was evaluated throughout with feedback from
      students and faculty. RESULTS: We were successful in establishing CBL. Study
      group (n=57) students scored better in SAQ((short Answer question) and
      EMQ((extended matching question)) assessment, (Mean study 21.15+/- 4.0565,
      control 18.5357+/-3.8632, n=56, p value 0.01.) Students appreciated it as good
      learning activity  STATISTICAL DESIGN: SAQ and EMQ, are compared in study vs.
      control groups by unpaired 't' test & also by equivalent non-parametric Mann
      Whitney test CONCLUSION: The training of doctors is too important an activity for
      bold experiments to be conducted without discovery what really happens. We had
      success in establishing Case based learning with faculty of almost all
      departments participating in the project as Resources. Although size of sample is
      small, CBL is found to be an effective modality of imparting medical education
      with effective integration of all departments.

PMID- 23132978
TI  - The Limberg flap for cutaneous defects - a two year experience.
AB  - AIM: To evaluate the Limberg or rhomboid flap done during the past 2 years with
      regard to applicability, reliability and complications. METHODS: All Limberg
      flaps done were reviewed by inspecting case records and directly following up
      patients. The indications, suitability, post-operative course and complications
      were noted. RESULTS: Eleven Limberg flaps were done during this period. Seven
      patients underwent the procedure for cutaneous malignancies. Rest for various
      benign lesions. All the flaps survived. One patient developed a hematoma under
      the flap. A significant cosmetic defect was noted in two patients. CONCLUSION:
      The Limberg flap is a safe and reliable flap for the coverage of various
      cutaneous defects if properly planned.

PMID- 23132979
TI  - Immunosuppression strategies after liver transplantation: a single centre
      experience in 57 liver transplant recipients.
AB  - CONTEXT: The art of administering immunosuppression lies in the ability to
      achieve a delicate balance between rejection and infection, thus maximizing
      patient survival and minimizing morbidity. AIMS: To analyze the effect of
      immunosuppression strategies following liver transplant on the incidence of acute
      rejection, bile leak, renal dysfunction and posttransplant graft unrelated
      infection. SETTINGS AND DESIGN: A retrospective analysis of immunosuppression
      regimens in 57 liver transplant recipients between Jan 1998 to July 2004 at a
      single institution. METHODS AND MATERIAL: For the purpose of study, the patients
      were divided into two groups: A - Cyclosporine based therapy (n=37), and B -
      Tacrolimus based therapy (n=20). In addition, both groups received Azathioprine
      or Mycophenolate mofetil with steroids. There were two subgroups in each Group A
      and B: Group C - Received induction using IL2Rab (n=5), and D - Where Sirolimus
      was used instead of Mycophenolate mofetil (N=7). The subgroups were equally
      distributed among the basic groups. The regimen was started based on one of the
      standard protocols but changes were made according to the clinical status of each
      patient. STATISTICAL ANALYSIS USED: The statistical analysis was done using Chi
      square test on SPSS12. RESULTS: A lower incidence of rejection was observed in
      Tacrolimus group compared to Cyclosporine group. There was an unacceptably high
      incidence of bile leak in patients where Sirolimus was used as an adjunct. IL2Rab
      enabled us to maintain a lower trough level of Tacrolimus for maintenance and
      enabled us to discontinue steroids earlier. CONCLUSIONS: Based on this study we
      dropped Sirolimus from our immunosuppression protocol and the encouraging results
      obtained with tacrolimus based therapy have supported its use as standard therapy
      in our immunosuppression regimens.

PMID- 23132980
TI  - Columnar cell lesions of the breast - significant or not?
AB  - Columnar cell lesions (CCL) of the breast range from the innocuous CAPSS
      (Columnar alteration with prominent apical snouts and secretions) to DCIS. Their
      precancerous potential poses diagnostic and therapeutic riddles, especially for
      those with mammographic microcalcifications. AIM: To document the incidence of
      columnar cell lesions in the breast, to study their morphologic spectrum and to
      study the significance of their association with benign and malignant breast
      lesions. MATERIAL AND METHODS: We studies 100 consecutive breast specimens. These
      specimens included biopsies, lumpectomies and mastectomies. Columnar cell lesions
      were classified as per Schnitt criteria. Associated lesions in the adjacent
      tissue were also studied. RESULTS: Of the 100 samples (43 malignant and 57
      benign), 37 cases showed CCL: CAPSS 23, columnar cell hyperplasia-11 and Columnar
      cell hyperplasia with atypia-3. The commonest associated lesion was fibrocystic
      change (n=54). Their incidence in benign and malignant lesions was 42% and 30%
      respectively, with no statistical significance in the difference. Lesions with
      atypia were seen only in malignant cases. CONCLUSION: Columnar cell lesions are
      common, and often overlooked. These lesions are seen in association with both
      benign and malignant breast lesions. It is only the presence of atypia in CCL
      that warrants a special mention and necessitates follow up, and resection if
      indicated.

PMID- 23132981
TI  - Evaluation of negative appendicectomy rate in cases of suspected acute
      appendicitis and to study the usefulness of ultrasonography in improving the
      diagnostic accuracy.
AB  - CONTEXT: Acute appendicitis poses a significant diagnostic challenge to the
      surgeon. Despite modern advances, the diagnosis of appendicitis remains
      essentially clinical. Ultrasonography is effective in supplementing the clinical
      diagnosis. AIMS: This study aims to evaluate the negative appendicectomy rate in
      patients subjected to appendicectomy and to assess the usefulness of ultrasound
      in improving the diagnostic accuracy. SETTINGS AND DESIGN: It is a retrospective
      review of prospectively collected data on 118 patients operated for suspected
      acute appendicitis in a single surgical unit between May 2001 and December 2002.
      METHODS AND MATERIAL: The detailed history, clinical examination and preoperative
      investigations according to protocol were recorded on a proforma. All patients
      underwent an ultrasonography of whole abdomen including pelvis. Each patient with
      suspected acute appendicitis was subjected to surgery and appendix was submitted
      for histopathological examination. The negative rate of appendicectomy,
      sensitivity and specificity of ultrasonography and positive and negative
      predictive value of ultrasound were calculated. RESULTS: The negative
      appendicectomy rate was 23.72%. In males it was 13.43% and in females 37.25%.
      Ultrasonography had a sensitivity of 63.33 % and a specificity of 82.14 %. The
      predictive value of a positive test was 91.93% and the predictive value of a
      negative test was 41.07%. CONCLUSIONS: The clinical diagnosis of acute
      appendicitis when supplemented with an ultrasonography, can achieve a reasonable
      degree of diagnostic accuracy with resultant low negative exploration rates
      thereby reducing the financial burden and morbidity by avoiding unnecessary
      appendicectomy and keeping the cost of treatment affordable.

PMID- 23132983
TI  - A case of primary rhabdomyosarcoma of the breast.
AB  - Primary rhabdomyosarcoma of the breast is a rarely reported in adults, and it
      occurrence is mostly observed in children. We report a case of primary
      rhabdomyosarcoma of breast in a 40-year-old lady, who presented in early stage
      and is in complete remission after one year of treatment.

PMID- 23132982
TI  - Ruptured left gastroepiploic artery aneurysm - a diagnostic dilemma.
AB  - We report a case of a 63-year-old man who presented to Accident and Emergency
      department (A&E) with dizzy spells and falls of sudden onset, without any obvious
      cardiac or vestibular abnormality. He had significant co-morbidity and rupture of
      the left gastroepiploic artery aneurysm. The atypical presentation and rarity of
      the case posed a diagnostic dilemma. Once the diagnosis was established by
      computerised tomography (CT), treatment was uncomplicated with good recovery.

PMID- 23132984
TI  - Perianal giant condyloma acuminata [buschke lowenstein tumour] - first case
      report from the Kashmir valley.
AB  - Buschke Lowenstein tumour or giant condyloma acuminata is a rare entity with only
      less then 50 cases reported in English literature so far. No such case has been
      reported from the Kashmir valley. They are considered as intermediate lesions
      between simple condyloma acuminata and invasive squamous cell carcinoma. A 57
      year-old heterosexual male presented with a giant perianal condyloma. The lesion
      was surgically excised completely. Postoperatively patient was put on topical 5
      FU ointment. Patient is recurrence free 6 months after surgery. The giant
      condyloma acuminate is an aggressive tumour with propensity for recurrance and
      malignant transformation. Surgical excision is the treatment of choice. One such
      rare case is discussed with review of literature.

PMID- 23132985
TI  - Severe gastrointestinal haemorrhage due to primary intestinal kaposi's sarcoma -
      a case report.
AB  - Kaposi's Sarcoma (KS) was previously a relatively rare disease. With the advent
      of HIV/AIDS pandemic however, AIDS-related KS has been on the increase and so has
      interest in the disease. Ninety percent of patients with KS present with skin
      lesions. While the gastrointestinal tract is a fairly common site of metastatic
      KS, primary gastrointestinal KS is uncommon. The presentation of gastrointestinal
      KS with severe gastrointestinal bleeding is rarer still. In this report, we
      present a 56-year-old HIV-negative patient who presented with severe
      gastrointestinal bleeding without any skin lesions. Multiple hemorrhagic
      polypoidal lesions were found on the walls of the jejunum and ileum as well as
      the liver at exploratory laparotomy and these were found to be KS on
      histopathologic examination. We also discuss the diagnostic and therapeutic
      challenges we had with this rare cause of severe GI bleeding.

PMID- 23132986
TI  - Benign multilocular cyst or multilocular cystic nephroma in adults: three case
      reports.
AB  - Multilocular cystic nephroma is an unusual entity of uncertain etiology that
      typically arises from the renal parenchyma. We report three such cases in adult
      females, in their fourth and fifth decades. Since existing imaging modalities
      cannot definitely exclude the possibility of multilocular cystic renal cell
      carcinoma these patients should undergo surgery.

PMID- 23132987
TI  - Giant chondrosarcoma of shoulder girdle.

PMID- 23132988
TI  - Blunt trauma to the parotid gland in an adult.

PMID- 23132989
TI  - Tension-free inguinal hernia repair comparing 'darn' with 'mesh': a prospective
      randomized controlled clinical trial.

PMID- 23132990
TI  - Winds of change: New UK immigration rules and future of surgical training for
      overseas graduates.

PMID- 23132991
TI  - Healthy India: paradigm shift in policy to achieve universal health care.

PMID- 23132992
TI  - Pancreatic anastomosis after pancreaticoduodenectomy: how we do it.
AB  - While mortality following pancreaticoduodenectomy has progressively decreased
      over the last decade, its morbidity, especially the development of pancreatic
      fistula, has remained constant over the years. However, high volume centers and
      individual surgeons report a major decrease in the rate of post-operative
      pancreatic fistulas. Technical refinements are crucial to reduce, and if possible
      prevent, the development of pancreatic fistula. No uniformity of opinion exists
      as to the method of pancreatic anastomosis after resection and few reports
      provide a detailed description of the actual technique employed. This article
      illustrates step-by-step the technique of pancreaticojejunostomy as practiced by
      the authors. Apart from presenting our previously published experience, results
      from other centres around the world are also provided in this review article.

PMID- 23132993
TI  - Surgical management of aneurismal dilation of vein and pseudoaneurysm
      complicating hemodialysis arteriovenuos fistula.
AB  - BACKGROUND: Pseudoaneurysm (PS) and aneurismal dilation of vein (ADV) are
      recognized complications of arteriovenous fistulas (AVF) in patients on
      hemodialysis. We present our experience about surgical management of these
      complications, which resulted in AVF preservation for continuing hemodialysis.
      MATERIAL AND METHODS: Twenty-two patients underwent surgical repair of an
      aneurismal dilation of vein or a pseudoaneurysm arising from a native AVF. In 14
      patients the aneurismal dilation of vein arose from the venous limb of AVF and in
      eight patients the pseudoaneurysm arose from an arteriovenous anastomotic site in
      the antecubital and anterior part of arm. The mean follow-up period was 15
      months. Clamp Aneurysm Repair (CAR) was performed to repair the aneurismal
      dilation of venous limb of AVF and Tourniquet Aneurysm Repair (TAR) was performed
      to repair PS that arose from AVF in the antecubital and anterior part of arm.
      RESULTS: In eight of the 14 patients with aneurismal dilation of vein, who
      underwent CAR procedure, vascular access was preserved. In three patients with
      aneurismal dilation of vein in snuffbox and one in forearm, the AVF had failed
      due to prior venous thrombosis of AVF. In two of 14 patients, there was no need
      for preservation of AVF because of renal transplantation. The technical success
      rate and patency rate during follow up period in CAR method was 100%. In seven of
      eight patients with psudoaneurysm in the antecubital and anterior part of arm,
      who underwent TAR procedure, the AVF remained patent. The technical success rate
      in TAR method was 87.5%, and the patency rate was 87.5%. Overall, technical
      success rate was 95.45% and patency rate was 93.75%. During the 15 months of
      follow up period hemodialysis program through the repaired AVF sustained as
      desired. CONCLUSIONS: The surgical methods used in our study could effectively
      repair the aneurismal dilation of vein and psudoaneurysm arising from a native
      AVF, and it lead to preservation of the AVF patency for continuing hemodialysis.
      These methods are technically feasible, safe and cost-effective procedures. It
      does not require dissection and additional incision for control of the vein and
      artery proximal and distal to the aneurismal dilation of vein and pseudoaneurysm;
      result in shorter time of procedure without complications.

PMID- 23132994
TI  - Role of gastric bypass in patients with unresectable advanced carcinoma of
      stomach.
AB  - CONTEXT: Role of bypass as a palliative surgery for advanced gastric cancer
      remains controversial. AIMS: To determine the role of bypass in advanced gastric
      cancer in comparision to resection as gold standard. DESIGN: Hospital based
      retrospective outcome study METHODS: Patients were divided into three groups:
      group I (gastric resection), group II (bypass) and group III (exploratory
      laparotomy alone). The three groups were analysed for palliation of symptoms,
      operative morbidity & mortality and survival. STATISTICAL ANALYSIS USED: Chi
      square, Fischer, One-way Anova, Unpaired-t, Kaplan-Meier analysis RESULTS: In
      hospital morbidity was 19.38% (19 patients) for the entire study group. Bypass
      group had a lower morbidity rate as compared to the resection group (p=0.029).
      Inhospital mortality rate was 6.12% (6 patients) for the entire study group.
      Mortality rates did not differ between the groups. Patient satisfaction with
      palliation of symptoms was similar between gastric bypass and resection. Gastric
      resection group had significantly better survival (p=0.002) compared to the non
      resective procedures. However, gastric bypass did not confer any survival benefit
      over exploratory laparotomy. (p=0.501)kw]Conclusions Gastric bypass can be done
      when resection is not possible as it palliates symptoms on par with resection and
      is associated with low operative morbidity though it does not improve the
      survival outlook of patients.

PMID- 23132995
TI  - High quality surgical care at low cost: the diagnostic camp model of Burrows
      Memorial Christian Hospital (BMCH).
AB  - BACKGROUND: The major problems that patients in rural areas face are related to
      accessibility, affordability and availability. AIMS OF THE STUDY: This study aims
      to evaluate how effectively the Diagnostic Camp Model of the institution meets
      the surgical needs of rural patients, by examining the logistics, economics and
      extent of the service provided. SETTINGS AND DESIGN: A retrospective study of
      patients attending the Diagnostic camps run by the staff of BMCH including the
      follow-up of these patients at the hospital. MATERIALS AND METHOD: The diagnostic
      camps involve transporting medical personnel and modern diagnostic equipment into
      the interior villages of various North Eastern states of India. Patients
      requiring surgical intervention later attend the hospital for surgery with the
      assistance of a health insurance scheme. STATISTICAL ANALYSIS: The local C3MDS
      computer software was used to obtain statistical reports from a diagnostic camp
      held at Saiha, Mizoram. Previous hospital data and the Government of India census
      were used to estimate the number of men requiring surgical intervention for
      Benign Prostatic Hyperplasia (BPH). RESULTS: About three quarters of surgical
      patients, who attended the surgical camp were unaware of their diagnosis prior to
      the camp. There was an overall profit despite the expected losses at the
      Hospital. These camps are a feasible and profitable venture on their own. About
      50% of patients estimated to require surgical intervention for BPH in three
      districts of Mizoram received the necessary interventions. CONCLUSION: This model
      is an attractive, cost effective, efficient way of meeting the surgical needs of
      patients from a large geographical area.

PMID- 23132996
TI  - Primary aneurysmal cyst: bone type in the breast.
AB  - A 60-year-old women presented with one month's history of a large breast lump. On
      examination she had irregular hard mass occupying the central and outer quadrants
      of the right breast with no palpable lymph nodes. Fine needle aspiration cytology
      (FNAC) diagnosis was a benign stromal lesion. In view of the large size, a simple
      mastectomy was performed. We are reporting this case of primary extrasseous
      aneurysmal cyst of the bone in the breast as the first case described in the
      literature.

PMID- 23132997
TI  - Tumoral calcinosis: a case report.
AB  - Tumoral Calcinosis is a distinct clinical and histological entity that is
      characterized by large periarticular deposits of calcium resembling a neoplasm
      and is found foremost in the region of hip, shoulder and elbow. We report a case
      of Tumoral Calcinosis in a 25-year-old male who presented to us with gradually
      increasing swelling of right axilla, and both hips of nearly two years duration.
      It was diagnostic enigma for the treating surgeons but with the help of an astute
      pathologist we diagnosed this rare condition and successfully treated it
      surgically.

PMID- 23132998
TI  - Desmoplastic fibroma of mandible in a child: case report.
AB  - The aim of this report is to present a rare case of a child with a desmoplastic
      fibroma (DF) at the mandibular angle. This lesion commonly shows a radiolucent
      and radiopaque radiographic picture. Due to its aggressiveness and high
      recurrence rate, an early diagnosis is essential and the complete removal of the
      lesion is the treatment of choice. We present a case of 11-year-old boy who was
      referred to be treated for an growth in the left mandibular angle area, a
      radiolucent and radiopaque feature. After an incisional biopsy, the complete
      removal of the lesion was done without vascular or nerve damage of the inferior
      alveolar bundle and without causing mandibular discontinuity. The clinical and
      radiographic features suggested the diagnosis and allowed the differentiation of
      DF from other lesions in the maxillofacial area. However, the final diagnosis was
      only possible through histopathological examination.

PMID- 23132999
TI  - Inferior gluteal artery pseudoaneurysm mimicking gluteal abscess.
AB  - We report a case of pseudoaneurysm of inferior gluteal artery initially diagnosed
      as gluteal abscess. Pseudoaneurysms of inferior gluteal artery are rare. High
      degree of clinical suspicion is required in a patient presenting with a post
      traumatic swelling in the gluteal region. These aneurysms may present with very
      different clinical pictures. They can be diagnosed by Doppler ultrasound,
      computed tomography or magnetic resonance imaging. Mainstay of the diagnosis is
      by angiography and the preferred management with good clinical results is with
      angiographic embolisation.

PMID- 23133000
TI  - Congenital diaphragmatic hernia with gastric volvulus.
AB  - Gastric volvulus is a surgical emergency presenting in various forms. Association
      with diaphragmatic defect is well known. Here we describe three cases of gastric
      volvulus associated with diaphragmatic defect having varied presentations and
      their management. A rare case of gastric volvulus with complete gangrene of the
      stomach is also reported. Three types of gastric volvulus have been described
      depending on the rotation axis: organoaxial, mesentericoaxial and combination of
      both types. Operative treatment includes reduction, correction of underlying
      cause and gastropexy.

PMID- 23133001
TI  - A modified spreader for pyloromyotomy.
AB  - A modified spreader for pyloromyotomy is innovated for congenital hypertrophic
      pyloric stenosis. It was found safe, effective and useful.

PMID- 23133002
TI  - Congenital tumor of tongue.

PMID- 23133003
TI  - Alveolar soft tissue sarcoma: rare presentation of a rarer malignancy.

PMID- 23133004
TI  - Rudolph Matas (1860-1957): father of vascular surgery.

PMID- 23133005
TI  - Pediatric cardiac surgery: need of the hour.

PMID- 23133006
TI  - A good counseling can overcome legal problems.

PMID- 23133007
TI  - Morphology of liver.
AB  - BACKGROUND: Liver size is related to body surface area. The present study was
      conducted to assess liver size and to find its relationship with body parameters.
      Also, the external surface of liver was studied for presence of fissures, which
      may demarcate the vascular segments and the blood vessels beneath them and may
      help the surgeon for resection of liver segment. MATERIAL AND METHODS: Apparently
      normal liver specimens were obtained from 50 cadavers aged 19-65 years.
      Measurements of liver diameters were taken with the help of Vernier Calipers.
      Volume of liver was taken by water displacement method. Means and standard
      deviation of data were calculated and liver dimensions were co-related with body
      parameters. RESULTS: The mean maximum transverse diameter was 199.4 + 24.5 mm and
      maximum vertical diameter was 149.5 + 18.7 mm. Significant correlations were
      observed between Maximum anteroposterior diameter and body mass index (p <
      0.05);Vertical diameter at falciform ligament and body weight (p < 0.01);Highly
      significant correlation was seen between liver volume and body surface area (P <
      0.001). The fissures showed underlying veins draining into the inferior vena cava
      in 40% cases. CONCLUSIONS: A significant increase in the body parameters with a
      corresponding increase in the liver dimensions was found. Study of morphology of
      liver can help the surgeons to dissect in proper planes to make the resection
      safe. The surface of liver showed 1-3 fissures distributed on all lobes in 70%
      specimens demarcating the vascular segments, which may help the surgeon during
      resection of liver.

PMID- 23133008
TI  - Ultrasound guided hydrostatic reduction of intussusception in children by saline
      enema: our experience.
AB  - BACKGROUND: Intussusception is a common cause of acute intestinal obstruction
      with potentially serious complications. The treatment of choice is an attempt at
      initial non-operative treatment. AIM: The purpose of the study was to evaluate
      the efficacy of the technique of hydrostatic reduction of intussusception using
      saline enema and ultrasound being practiced in our institute; the secondary goal
      was to identify patient subset in which it is more successful. MATERIAL AND
      METHODS: The case records of all patients treated for intussusception in our
      institute from 1st January 2000 to 30th June 2007 were retrospectively analyzed
      to collect information. All patients with ultrasound diagnosed intussusception
      that were not having signs of shock or peritonitis were treated with normal
      saline enema under ultrasound guidance. Failure of three such attempts was an
      indication for operation. RESULT AND CONCLUSIONS: We found that this technique is
      easy, safe and extremely effective in treating intussusception in children. The
      success rate was 81.37% (83 out of 102 cases) and mortality rate was 1.2%.
      Ileoileocolic type of intussusception failed enema reduction more often
      (statistically significant; P value = 0.0032) while older patients (statistically
      significant, P value = 0.001) had higher success rates with the technique.
      Patients who had colocolic type of intussusception (P value = 0.29) and patients
      who present early (P value = 0.262) appear to have higher success rates but this
      was not statistically significant.

PMID- 23133009
TI  - A study of knowledge, attitude and practice of hospital consultants, resident
      doctors and private practitioners with regard to pre-hospital and emergency care
      in Lucknow.
AB  - BACKGROUND: Burden of death and disability resulting from lack of emergency
      medical system (EMS) and emergency care is very high in low and middle income
      countries (LMIC). AIM: To study the knowledge, attitudes and practices of pre
      hospital care and emergency services among health care providers of Lucknow
      SETTING AND DESIGN: Cross-sectional survey, 200 residents, 104 hospital
      consultants and 108 private practitioners MATERIAL AND METHODS: A close ended,
      self administered questionnaire based on 5-point Likert scale with 30 items of
      knowledge, attitude and practice of pre-hospital and emergency care RESULTS:
      Median scores of knowledge (26/50), attitude (41/50) and practices (27/50) showed
      less than adequate knowledge and practices. However, a positive attitude was seen
      in all the 3 group of respondents i.e. resident doctors, hospital consultants and
      private practitioners. CONCLUSION: Lucknow is the capital city of Indian largest
      state - Uttar Pradesh with over 100 years of established medical education. The
      results of the study in this town are applicable to most developed cities in
      India. Lack of adequate knowledge and practices in emergency medical system (EMS)
      at Lucknow represent a dismal situation and require continuing medical education
      in this area.

PMID- 23133010
TI  - Management of hemorrhage of retro hepatic inferior vena cava injury during piggy
      back technique for liver transplantation.
AB  - BACKGROUND: Injury to large abdominal vessels is still one of the most terrifying
      results of trauma or intraoperative faults, as the management of the hemorrhage
      is hardly difficult due to being torrentially and unaware of the proper
      reparation. The controversial problem is which technique should be preferred in
      case of injury to RHIVC and how can it be managed with minimal risk. PATIENTS AND
      METHODS: Over two-year period, we retrospectively analyzed the patients who had
      undergone adult-to-adult liver transplantation and collected data about the
      injuries to RHIVC during recipient hepatectomy. All patients were treated with
      the same surgical technique including digital compression and continuous suturing
      the tear. RESULTS: Twenty five patients (21 male, 4 female) were detected. The
      causative factors for end stage liver disease included hepatitis B, hepatitis C
      with or without hepatocellular carcinoma, autoimmune hepatitis, alcoholic
      hepatitis, cryptogenic hepatitis, Wilson disease, and nonalcoholic
      steatohepatitis. Mean diameter of the injury was measured 0.5 cm (range: 0.2
      1.6). Only three patients (12%) had more than one injury. Mean amount of blood
      loss between injury and repair was 130 cc (40-350 cc). There was no operative
      mortality. CONCLUSION: Calmness of the operative team followed by the appropriate
      surgical approach is the key of the success in case of any injury to RHIVC.
      Digital compression technique can be enough to prevent massive bleeding and
      repair the injury tract without any vascular exclusion that may result with
      serious postoperative complications. We proposed this technique because of its
      ability by most surgeon and easy to perform in a safe way.

PMID- 23133011
TI  - Urological manifestation of delayed complication of laparoscopic cholecystectomy.
AB  - Gallstone spillage is recognised as a possible complication of laparoscopic
      cholecystectomy and there are countless examples of untoward short and long term
      sequelae resulting from their non-retrieval. We present the case of a 65-year-old
      gentleman with sterile pyuria and lower midline abdominal mass which proved to be
      a complex gallstone inflammatory mass related to the dome of the bladder. This
      patient's investigative course was exhaustive and the definitive diagnosis not
      achieved until histopathological assessment of the intraoperative specimen. The
      diagnosis of these lower abdominal wall masses can be difficult, particularly
      with complex lesions.

PMID- 23133012
TI  - Cytomegalovirus colitis presenting as massive lower gastrointestinal bleeding in
      an immunocompetent patient.
AB  - Cytomegalovirus infection is ubiquitous but often remains asymptomatic in
      affected patients. Symptomatic cytomegalovirus infection usually occurs in
      immunocompromised patients- patients who are infected with the Human
      Immunodeficiency Virus, have received organ transplantations, or are on
      immunosuppressive therapies. Cytomegalovirus colitis can present with abdominal
      pain, diarrhea and significant per rectal blood loss. It is a rare entity in
      immunocompetent patients and can often be missed unless one has a high index of
      suspicion. We describe a case of CMV colitis in a 78-year-old patient with no
      known risk factors for immunosuppression who was admitted for respiratory
      diseases and then subsequently developed transfusion dependent lower
      gastrointestinal bleeding. She ultimately required surgical resection of her
      colon. A literature review on CMV colitis, its myriad manifestations and
      therapeutic outcomes was conducted, with particular emphasis on its occurrence in
      immunocompetent patients.

PMID- 23133013
TI  - A rare case of bilateral basal cell adenomas in the parotid glands.
AB  - We report a very rare case of bilateral parotid tumors in a 55-year-old female
      patient who presented with left parotid mass of 7 * 7 cm size since 8 years and
      right parotid mass of 2.5 * 1.5 cm size since 2 years duration. Based on clinical
      features a provisional diagnosis of bilateral pleomorphic adenomas was made.
      Results of fine needle aspiration cytology of both masses were inconclusive.
      Bilateral superficial conservative parotidectomy with facial nerve preservation
      revealed bilateral encapsulated and lobulated tumors which on histopathological
      examination revealed bilateral basal cell adenomas in both parotid glands.

PMID- 23133014
TI  - Inferior vena caval injury following self-inflicted abdominal stab wound.
AB  - A rare case of attempted suicidal abdominal stabbing using a shoemaker's piercing
      awl is reported. The patient presented with the weapon still in place. On
      emergency exploration, injury to the inferior vena cava and the inferior
      mesenteric artery were found. The case highlights the fact that major vascular
      injury may be present in patients of abdominal stabs with retained weapons
      inspite of their haemodynamic stability. It also illustrates the importance of
      manipulating retained weapons only after complete exposure with adequate
      preparation for a vascular procedure.

PMID- 23133015
TI  - Jejunal GIST with extramural hemangiomatous component presenting as an obscure
      lower GI bleed: a case report.
AB  - GISTS (Gastrointestinal stromal tumours) are malignant form of sarcoma of the
      digestive tract. Various unusual presentations and morphological variants of GIST
      have been described, including extramural components of GIST. The literature has
      no reference regarding an extramural hemangiomatous component of a GIST. Here we
      present a case of 54-year-old women with this unusual morphological condition
      presenting as an obscure lower GI bleed. Diagnosis in this case was made by
      subjecting the resected specimen to immunohistochemical analysis.

PMID- 23133016
TI  - A case of retropharyngeal Lipoma.
AB  - Lipomas are one of the most common benign mesenchymal tumors in the body. Usually
      asymptomatic, they rarely warrant treatment unless they attain enormous size
      causing cosmetic deformity or pressure effects. Head and neck region is an
      uncommon site, retropharyngeal space being one of the rarest. Lipomas in this
      region can produce pressure symptoms demanding surgical excision.This is a case
      report of retropharyngeal lipoma, extending from skull base to the clavicle.
      Though tumor was present for 20 yrs it exhibited rapid growth over a period of 2
      3 yrs causing respiratory obstruction, dysphagia & dysphonia. Clinically the
      entire laryngopharynx, trachea and carotid sheath were pushed anteriorly. On
      imaging, it showed classical features of a lipomatous mass. Patient underwent
      complete excision which presented a surgical challenge to surgeon and the
      anaesthetist from intubation to extubation.

PMID- 23133017
TI  - Delayed pancreatoduodenectomy post SEMS.

PMID- 23133018
TI  - Superscan in carcinoma prostate.

PMID- 23133019
TI  - Cancer becoming a chronic disease not a death sentence!!

PMID- 23133020
TI  - Fibroadenoma.

PMID- 23133021
TI  - Indian Journal of Surgery - few steps into the future.

PMID- 23133022
TI  - Traumatic diaphragmatic hernia.
AB  - BACKGROUND: Abdominal trauma is frequently encountered, but traumatic injuries to
      the diaphragm are often missed. MATERIAL AND METHODS: A retrospective review of
      all the case files of patients presenting with traumatic diaphragmatic injury was
      performed. These patients were analyzed for their presentation, injury, surgery
      performed and outcome RESULTS: A total of 14 patients were thus identified (12
      males and 2 females). The average age was 31.5 years. Road traffic accidents were
      the most common cause, accounting for the majority of cases (12 patients). 10
      patients presented within 24 hours of injury; the other 4 presented late (2 1/2
      months to 20 years) with the signs and symptoms of acute intestinal obstruction.
      The left side of the diaphragm was injured more commonly. Herniation of multiple
      intra abdominal viscera was common, with the stomach being the organ most
      commonly implicated. There were 2 deaths. CONCLUSIONS: Traumatic injury to the
      diaphragm must be kept in mind while dealing with patients who have sustained
      abdominal trauma. The diagnosis can easily be picked up on chest x-ray. Treatment
      is surgical, with simple suturing of the diaphragm with non-absorbable suture
      giving good result.

PMID- 23133023
TI  - The pattern of the descent of PTH measured by intraoperative monitoring of intact
      PTH in surgery for renal hyperparathyroidism.
AB  - BACKGROUND: In the setting of total parathyroidectomy and autotransplantation
      surgery (TPTxAS) treatment for secondary hyperparathyroidism (SHPT) we evaluated
      whether intraoperative parathyroid hormone (iPTH) monitoring is an useful tool as
      a reference for total parathyroid removal. DESIGN: Prospective open single value
      measurement efficacy study of one intraoperative (i.o.) diagnostic monitoring
      method (iPTH) on a cohort of surgical patients. PATIENTS: All patients (n = 35)
      undergoing TP and SCTx at the Department of Surgery, Donostia Hospital from
      January 2002 to December 2006. MAIN OUTCOME MEASURES: Serum levels of iPTH during
      surgery and prediction time of the of descent of PTH levels (measured in the
      clinic, at admission day and intra-operatively during induction of anesthesia,
      and every 5 and 10 minutes after removal of adenoma and 24 hours thereafter) were
      analyzed. RESULTS: iPTH levels dropped clearly at ten minutes in all 35 patients
      and were non-measurable at 24 hours. iPTH decreased from pathological (1302.24 +
      424.9 pg/ml) to half (50%) the values at the third intra-operative determination 
      minute 10 - (614.8 +/- 196.62) and was undetectable at 24 hours. CONCLUSIONS:
      Intra-operative measurement of iPTH is useful in the prediction of complete
      removal of all parathyroid tissue prior to autotransplantation thus avoiding
      persistence because of incomplete surgery.

PMID- 23133024
TI  - Clinical spectrum of discharges against medical advice in a developing country.
AB  - BACKGROUND: Patients who leave the hospital before clinician certification of
      fitness are referred to as discharge against medical advice (DAMA). This
      phenomenon of discharges against medical advice is an undesirable but relatively
      common occurrence worldwide. Professional liability and harmful effect of this
      practice to individual health are of concern. AIMS: The essence of this study is
      to determine the spectrum of patients who DAMA in a Nigerian teaching hospital.
      DESIGN: Descriptive study over a two-year period in an urban teaching hospital in
      Nigeria. MATERIALS AND METHODS: All consecutive patients who discharge against
      medical advice at the surgical emergency room of University Teaching Hospital,
      Ilorin from January 2004 to December 2005 were studied prospectively. The
      patients' demographic details, diagnosis, reason for discharge, signatory to
      discharge and length of hospital stay were studied. STATISTICAL ANALYSIS:
      Analysis of the data was done using Statistical Package for Social Sciences
      (SPSS) version 11. RESULTS: Prevalence rate of DAMA was 4.2%, comprising 110 of a
      total of 2,617 patients admitted during the study period. Male to female ratio
      was 3.8:1, the mean age was 30.0 years (range, 4-70 years). Trauma accounted for
      the highest number of patients 102(97.2%) out of whom 52 (51%) had long bones
      fracture. Patients who wish to seek alternate medical care accounted for 43.6%,
      while financial constraint contributed to 29.1% DAMA. Forty-five out of forty
      eight (93.7%) of patients who DAMA to seek alternate medical care had fracture.
      CONCLUSION: Trauma was the most common clinical condition for patients who DAMA.
      Most common reason for DAMA was to seek alternate treatment followed by financial
      constraint. Health education on potential benefit of orthodox treatment of
      fracture, treatment subsidy and full implementation of national health insurance
      scheme will reduce incidence of DAMA.

PMID- 23133025
TI  - Temporal artery biopsy: impact on the clinical management of patients.
AB  - OBJECTIVES: Temporal artery biopsy (TAB) is requested in an attempt to confirm
      the diagnosis of temporal arteritis (TA). Patients symptoms and signs are highly
      variable and TA is often focal and potentially missed in a small biopsy. The
      study aimed to determine if TAB helps in the management of patients with
      suspected TA. METHODS: The case records of sixty-six consecutive patients who had
      undergone temporal artery biopsy were recalled and examined for presenting
      symptoms, management, therapy, results and outcome. RESULTS: There were 23 men
      and 43 women with a mean age of 70.2 and 71.1 years respectively. Presenting
      symptoms varied with unilateral headache in 53, scalp tenderness in 16, muscle
      weakness in 10, visual disturbance in 16, jaw claudication in 5 and peri-orbital
      pain in 1 patient. The temporal artery was tender in 21 patients and thickened in
      4 patients. Thirty-eight patients were commenced on steroids prior to biopsy and
      6 more before the histology became available. Only 8% of biopsies were positive
      for TA. Of the patients started on steroids with a negative biopsy, the steroids
      were continued in 26 and stopped in 9. In the patients not put on steroids [22],
      biopsy was positive in 2; they were commenced on steroids. Therefore, the
      histological diagnosis resulted in a change in patient management in only 18% of
      patients. CONCLUSION: The results of TAB do not appear to affect the clinical
      management of most patients with suspected temporal arteritis. We must therefore
      question the routine use of this invasive investigation.

PMID- 23133026
TI  - A rare cause of an abdominal mass.
AB  - A 57-year-old male presented with right upper abdominal lump since 3 months. He
      was diagnosed to have a hepatic artery aneurysm. He was investigated thoroughly
      but no cause was found. He was subjected to endovascular embolisation of the
      aneurysm using endovascular coils. Subsequently the aneurysm was completely
      occluded. Hepatic artery aneurysms are very rare among all visceral aneurysms. We
      report this rare case of hepatic artery aneurysm presenting as an abdominal lump.
      This case highlights the importance of early diagnosis and management of this
      rare entity as a rupture may be catastrophic.

PMID- 23133027
TI  - Accessory left hepatic artery arising from common hepatic artery.
AB  - The knowledge of anatomical variations in hepatic artery are of importance to
      surgeons and radiologists while performing complicated procedures like liver
      transplantation and transarterial chemo-embolization for hepatic tumors. The
      incidence of accessory left hepatic artery is less common than the right
      accessory hepatic artery. Here we report an anomalous accessory left hepatic
      artery arising from common hepatic artery in a 55 year old male cadaver.

PMID- 23133028
TI  - Wilkie's syndrome: an uncommon cause of intestinal obstruction.
AB  - A 10-year-old boy presented with 9 months history of gradually worsening,
      recurrent postprandial upper abdominal pain, bilious vomiting and loss of weight.
      On examination the child was undernourished, had epigastric fullness and
      succusion splash was positive. Ultrasonography of the abdomen suggested a
      massively distended stomach, while an upper gastrointestinal contrast study
      showed a hugely dilated stomach along with dilated first and second parts of the
      duodenum with abrupt cut off at the level of third part of duodenum. Contrast
      enhanced CT scan of the abdomen revealed dilatation of the second part of the
      duodenum without any obvious abnormality of the aorta-superior mesenteric artery
      angle. Upper gastrointestinal endoscopy showed retained fluid and food material
      within a dilated stomach and second part of the duodenum; scope could not be
      negotiated into the third part because of an extrinsic compression. The child was
      diagnosed to be suffering from Wilkie's syndrome. Exploratory laparotomy,
      performed when conservative management failed, revealed compression of the third
      part of duodenum by a shortened ligament of Trietz and dense peritoneal bands
      near the third part of duodenum. The duodenal obstruction was bypassed by
      performing duodenojejunostomy. The child had an uneventful postoperative
      recovery. He gained around 6.8 kilograms within next five months.

PMID- 23133029
TI  - Severe intraperitoneal injuries due to self introduced rectal foreign body.
AB  - Rectal foreign body insertion is an increasingly common surgical dilemma that
      requires thorough history, physical examination, radiographs and inventiveness to
      treat. Additionally the surgeon should demonstrate a sympathetic and caring
      attitude. This case report highlights the successful surgical management of a
      rare and bizarre case of extensive intraperitoneal injuries due to a wire
      inserted by the patient to retrieve a rectal foreign body introduced for sexual
      gratification.

PMID- 23133030
TI  - Successfully treated stump appendicitis diagnosed by CT and ultrasonography.
AB  - Although rare, inflammation of the appendiceal stump can occur and is still an
      important clinical entity. There has been a recent increase in interest in stump
      appendicitis. In this study a case of right lower quadrant pain in an 18-year-old
      man who underwent an appendicectomy 7 months previously is presented. Recurrent
      appendicitis was noted in an appendiceal stump during surgery which previously
      diagnosed by CT and ultrasonography.

PMID- 23133031
TI  - Accessory sulcus of the liver - an incidental laparotomy finding.
AB  - The diaphragmatic surface of the liver is normally smooth but may be grooved
      occasionally. Such grooves could be 'cough furrows' or due to a 'corset liver'.
      Accessory sulci have also been described and may confuse the inexperienced
      surgeon. We describe one such case of an accessory sulcus found incidentally at
      laparotomy.

PMID- 23133032
TI  - Pseudoaneurysm of the replaced right hepatic artery with arterio venous fistula
      to the portal vein.

PMID- 23133033
TI  - Franz kaspar hasselbach (1759-1816).
AB  - Franz Kaspar Hasselbach (1759-1816) was an eminent anatomist and surgeon,
      remembered for his invaluable contributions in fields of anatomy and surgery. He
      gave accurate discription of triangle of Hasselbach made almost 200 years back,
      and it forms the basis of classification of inguinal hernia and is the
      cornerstone for laparoscopic repair of hernia, unheard of in his era. He has a
      number of eponyms named after him.

PMID- 23133034
TI  - Letters to the editor.

PMID- 23133035
TI  - Indian Journal of Surgery - the platform for Indian surgeons.

PMID- 23133036
TI  - Idiopathic chronic orchialgia - a frustrating issue for the clinician and the
      patient.
AB  - Chronic testicular pain represents a management dilemma to clinicians and remains
      a very frustrating clinical problem. In nearly 25% of patients there is no
      obvious cause for idiopathic chronic orchialgia. Chronic testicular pain may
      occur at any age but the majority of patients are in 20-30 years of age group.
      The desired goal of the treatment is to allow the patient return to routine
      activity without significant use of analgesics. There is very little published
      material, in urology, about the etiology and treatment of idiopathic chronic
      orchialgia but situation is not bleak since many treatment options do exist which
      can allow the patient enjoy life with mechanisms for coping with pain. A
      multidisciplinary team approach is required, so that the patient can benefit from
      the different treatment options available at present.

PMID- 23133038
TI  - A prospective study of surgical site infections in a teaching hospital in Goa.
AB  - INTRODUCTION: Surgical Site Infections contribute significantly to increased
      health care costs in terms of prolonged hospital stay and lost work days. The
      problem was largely unexplored in an apex medical institute in Goa. AIMS AND
      OBJECTIVES: To estimate the incidence, and study the bacteriology and the factors
      associated with SSI in the study setting. SETTINGS AND DESIGN: Prospective study
      in the surgical wards of an apex medical teaching hospital in Goa. MATERIALS AND
      METHODS: Clinico-bacterilogical follow-up of 114 post-operative cases to the
      development of SSI, as per the CDC criteria (1991). Incidence was expressed as
      the infection rate per 100 operations. Antibiotic sensitivity testing was done
      using the disc diffusion method. STATISTICAL ANALYSIS: Association was tested by
      applying the Student t-test and the Chi-square test of significance, and the
      strength of association expressed as the Odd's Ratio. RESULTS: The overall SSI
      rate was estimated to be 30.7%; 5.4% for clean, 35.5% for clean-contaminated, and
      77.8% for contaminated operations. Seventy-nine per cent of the isolates were
      gram-negative and almost 64% demonstrated polyantimicrobial resistance.
      CONCLUSIONS: The study emphasizes the need for the evidence-based infection
      control and antibiotic prescription policies in the hospital.

PMID- 23133037
TI  - Sentinel lymphnode biopsy in early breast cancer using methylene blue dye and
      radioactive sulphur colloid - a single institution Indian experience.
AB  - BACKGROUND: Axillary lymph node dissection is an established procedure in breast
      cancer staging. However, it is associated with unpleasant side effects. A
      promising alternative to assess axillary lymph node status in early breast cancer
      patients is Sentinel Lymph Node Biopsy (SLNB). Isosulfan blue has traditionally
      been the dye used to identify the Sentinel Lymph Node (SLN). This article is a
      validation study of SLNB using methylene blue dye and radioactive sulphur colloid
      in early breast cancer Indian patients.  MATERIALS #ENTITYSTARTX00026; METHODS:
      With written informed consent, 100 patients with cytology or biospy proven
      carcinoma breast, clinical stage T1/ T2 N0 M0, underwent SLNB using combination
      of methylene blue dye & radioactive technetium 99m sulphur colloid as a part of
      validation study from June 2003 to February 2006. After validation study, from
      March 2006 to February 2007, 35 patients have undergone SLNB followed by complete
      axillary clearance in only those patients with SLNB being positive for
      metastases. RESULTS: In all 100 patients of the validation study SLN was
      identified. Total number of cases with positive axillary nodes was 27, out of
      which SLN was only positive node for metastases in 69% of cases. The overall
      sensitivity, specificity, positive predictive valve and negative predictive valve
      of SLNB 96.2%, 100%, 100% and 98.6% respectively with false negative rate of
      3.7%. In subsequent 35 patients who underwent SLNB followed by complete axillary
      clearance, SLNs was identified in all the cases. CONCLUSIONS: SLNB is effective
      in early breast cancer patients of Indian population. SLNB using combination of
      methylene blue dye and radio-active Tc99m sulphur colloid can stage the axilla
      with high accuracy & low risk of false negativity in early breast cancer
      patients.

PMID- 23133039
TI  - A one year prospective study to compare and evaluate diagnostic accuracy of
      modified Alvarado score and ultrasonography in acute appendicitis, in adults.
AB  - OBJECTIVES: To compare and evaluate diagnostic accuracy of modified Alvarado
      score and ultrasonography in co-relation to histopathology report for diagnosis
      of acute appendicitis. METHODOLOGY: A prospective study of the patients who
      underwent appendectomy for suspected acute appendicitis at K.L.E.S. Hospital and
      M.R.C. Belgaum. The clinical, radiological and ultrasonogrpahic data of 60
      patients with suspected appendicits was collected. These patients were evaluated
      by modified Alvarado here and ultrasonographically, which was correlated with
      histopatholocial finding. RESULTS: Out of 60 patients, 38.33% had acute
      appendicitis. 40% had modified Alvarado score >= 7 and 38.33% patients were
      ultrasonographically positive. In the present study, modified Alvarado score has
      sensitivity of 78.26%, specificity 83.78%, positive predictive value 75.00%,
      negative predictive value 86.11%, diagnostic accuracy 81.00% false positive error
      rate 16.22% and false negative error rate 21.74%. Ultrasonography had sensitivity
      of 82.61%, specificity of 89.19%, positive predictive value of 82.61, negative
      predictive value of 89.19.Diagnostic accuracy of 86.67%, false positive error
      rate of 10.81%, false negative error rate of 17.39%. When modified Alvarado score
      and ultrasonography were positive, 17 true positive cases and no false positive
      cases. The false negative cases in modified Alvarado score were five. When it was
      combined with ultrasonography the false negative cases reduced to two that is 60%
      reduction in false negative cases. CONCLUSIONS: Modified Alvarado score is useful
      tool in clinical decision making. When compared with ultrasonography neither one
      is advantageous. However, additional information provided by ultrasonography
      improves diagnostic accuracy.

PMID- 23133040
TI  - Cryosurgery and ligation (Cryo-plication) of symptomatic hemorrhoids - "an ideal
      procedure". Initial experience and review of literature.
AB  - Haemorrhoidal disease has been in limelight again due to emerging newer
      modalities of treatment over the last decade. The range varies from simple rubber
      band ligation to stapled rectopexy. But a rational and ideal approach is still
      unclear. This study aims to analyze the ideal modality in today's scenario of
      managing haemorrhoidal disease. A prospective study on 12 patients, was carried
      out over 24 months in a surgical unit of a tertiary care hospital. The pain,
      bleeding, rectal discharge, anal stenosis were observed. Results show that the
      Cryoplication procedure had no anal stenosis, minimal bleeding, less pain and
      cost was effective. When compared with other contemporary modalities it has
      lesser complications and short and easy learning curve.

PMID- 23133041
TI  - Urachal adenocarcinoma masquerading as an urachal cyst.
AB  - Urachal adenocarcinoma arising in the dome of the bladder or at the pre-existing
      urachal remnant is rare. An early case of urachal cyst harboring adenocarcinoma,
      clinically diagnosed as ovarian tumor, which was surgically removed with a good
      prognosis is reported.

PMID- 23133042
TI  - Ruptured inflammatory aortic aneurysm with aortoenteric fistula and infected with
      Streptococcus pneumoniae: a review of the literature.
AB  - We present a case report of a 65-year-old gentleman who presented with an
      aortoenteric fistula along with a review of the literature. He was found, in
      addition, to have an inflammatory infrarenal aortic aneurysm with a posterior
      rupture. Cultures of the aneurysm sac confirmed a Streptococcus pneumoniae
      infection. The patient had previously presented with pneumonia. Antibody testing
      revealed an isolated pneumococcal IgG deficiency. The case demonstrates the
      diverse pathologies associated with aortic aneurysms and a need to be vigilant
      and occasionally expect the unusual.

PMID- 23133043
TI  - True knot in Ryles tube: a case report.
AB  - Insertion of Ryles tube is a simple routine procedure. During its insertion,
      minor complications like trauma to nose, nasopharynx and oral cavity do happen
      from time to time. But as the Ryles tube is usually inserted blindly, potentially
      life threatening complications like inadvertent entry into trachea, cranial
      cavity and intravascular penetration have been reported. Folds and kinks may
      occur, but true knot of the Ryles tube, which we now report, is very rare.

PMID- 23133044
TI  - Pica - a case of acuphagia or hyalophagia?
AB  - Pica is an eating disorder typically defined as the persistent eating of
      nonnutritive substances for a period of at least 1 month at an age in which this
      behavior is developmentally inappropriate. Acuphagia being consumption of sharp
      objects and Hyalophagia consumption of glass materials. Majority of the foreign
      bodies ingested into the gastrointestinal tract pass through the rectum
      asymptomatically, where as objects which are sharp, long, jagged may not be able
      to pass through. These types of objects may cause complications like impaction,
      leading to intestinal obstruction, ulceration, perforation and bleeding, thus
      need surgical exploration. In this case of young female with impacted bunch of
      bangles in the stomach and few in the small and large bowel, who was completely
      asymptomatic, needed gastrotomy with enterotomy for complete and successful
      retrieval of glass bangles.

PMID- 23133045
TI  - Post operative recurrent acute jejuno-jejunal intussusception.
AB  - A case of recurrent acute jejuno-jejunal intussusception presenting in the post
      operative period of the surgery for acute ileocolic intussusception is presented.
      Post operative intussusception is defined as intussusception occurring within 30
      days of the primary surgery [1]. This is a rare entity. Jejuno-jejunal
      intussusception is also rare. Recurrent intussusception is uncommon. The present
      case is a combination of all these rarities.

PMID- 23133046
TI  - Rare case of neglected oesophageal safety pin in a seven month child.

PMID- 23133047
TI  - Retroperitoneal cystic lymphangioma.

PMID- 23133048
TI  - Continuous medical education programmes: our expectations.

PMID- 23133049
TI  - Comparative assessment of TNFinfinity and C-reactive protein in patients
      subjected to open instead of laparoscopic cholecystectomy. Indian J Surg 69(3):99
      104.

PMID- 23133050
TI  - Bedsores: "top to bottom" and "bottom to top".
AB  - Bedsore is a global problem concerning the bedridden, infirm, debilitated and
      malnourished patients in hospitals and community setups. The cost of treatment is
      enormous involving billions of dollars to nations and individuals. Mortality
      increases two to six times if bedsores are present. There is little research done
      despite its commonness to understand how they occur or why they occur; etiology
      is not much understood. The two theories called 'top to bottom' and 'bottom to
      top' contradict each other. It is thought that 'pressure', shear-stress' and
      'ischemia' may be causing it in some yet to be understood way.There is little
      awareness on how to prevent them or how to treat them if they do occur. Seldom
      applied, various scales exist and should be used to identify patients at high
      risk. Braden scale is the most tested and widely accepted scale. The various
      available dressings and pressure relief devices are mostly inadequately studied;
      which is superior is a question that begs an answer. This article aims to
      underline the importance of bedsores by reviewing our current and past knowledge
      with emphasis on practical implications thereof.

PMID- 23133051
TI  - Primary hyperparathyroidism: retrospective 10-year study of 32 cases.
AB  - BACKGROUND: Parathyroid glands are endocrine glands that regulate calcium
      metabolism. Usually four in number, they lie mostly on the posterior aspect of
      thyroid glands. Primary hyper-parathyroidism (PHPT) refers to a condition wherein
      they secrete an excess of parathyroid hormone leading to signs and symptoms of
      hypercalcemia. PATIENTS AND METHODS: Thirty-two patients of primary hyper
      parathyroidism were seen by us in the ten years. Majority of patients were below
      40 years of age (88%). Male: female ratio was 1:4. The diagnosis was made
      incidentally in patients who reported for various signs and symptoms not
      responding to treatment. High serum calcium pointed to the diagnosis of primary
      parathyroid hyperplasia. It was confirmed by high level of serum parathyroid
      hormone and localization of enlarged parathyroid glands by USG / MRI and / or Tc
      99 Technetium scan. Of the 32 patients examined, 43 parathyroid glands were
      excised, five cases had two glands excised; out of these 4 cases underwent
      parathyroid reimplantation in neck/forearm muscles. One unusual case underwent
      operation for giant-cell tumor of the head of humerus. This patient presented
      with excessive vomiting not responding standard medical management in post
      operative period. RESULTS: During investigations serum calcium was found to be
      very high, the diagnosis was confirmed by finding high parathyroid hormone and
      corroborated by T(99) Technetium scan. Parathyroidectomy was done in all cases,
      of which 59% (18 cases) developed mild to severe tetany due to hypocalcaemia.
      CONCLUSION: Primary hyperplasia of thyroid gland is the most important cause of
      hypercalcemia. Hypercalcemia is found in all cases of PHPT in our series with
      high parathyroid hormone levels. Majority of our cases have one gland involvement
      and hypocalcaemia in our series is unusually high following excision of involved
      gland.

PMID- 23133052
TI  - Evaluation of foot problems among diabetics in rural population.
AB  - INTRODUCTION: Diabetes is the most common metabolic disease encountered by a
      surgeon. A sound knowledge of symptomatology, clinical signs and etiology can
      prevent most of the disease burden and complications and thus reduce social
      burden. The study tells about common foot problems among diabetes and correlates
      it with the awareness among people. AIM AND OBJECTIVES: The study aims to obtain
      an initial and representative data sample to identify the common pedal
      complications of diabetes mellitus and to provide an initial projection for the
      development of a podiatric foot health education program within the Hospital
      Medical Centre Complex. MATERIALS AND METHODS: 500 diabetic patients were
      examined of whom 52 had diabetic foot lesions. The symptoms, signs and grade of
      foot lesion were cross studied with duration, type and occupation of patient. Chi
      square test was performed and a probability value of p <0.05 was considered
      significant. CONCLUSION: The prevalence of diabetic foot in a hospital based
      rural diabetic population was observed to be 10.4%. Foot lesion were common in
      the age group 41-60 years. The most common symptom was numbness in foot ( 40.6%)
      and was more common in long duration diabetes, Type II diabetes and outdoor
      workers. Common foot deformity observed were callosities (54.6%) and Hallux
      valgus/ varus (28%). The least common was Charcot's deformity (3.6%). Ulceration
      (23%) and amputation (5.7%) were higher in outdoor workers. Wagner's grade 2
      lesions were the most common foot lesion with diabetic foot. The questionare
      regarding knowledge, awareness and foot care showed. 99.8% did not inspect the
      feet properly and 74% washed their feet properly.

PMID- 23133053
TI  - Decompressive craniectomy: an effective but underutilized option for intracranial
      pressure management.
AB  - INTRODUCTION: Decompressive Craniectomy is an effective option in the management
      of intractable intracranial hypertension. AIM AND OBJECTIVES: Neuronal
      conservation can be achieved by aggressive decompression (hemicraniectomy).
      MATERIAL AND METHODS: In this series 12 patients with a Glasgow Coma Scale score
      of 8 or <8 with increased intracranial pressure underwent decompressive
      hemicraniectomy. RESULTS: The outcomes were prospectively evaluated. Eight
      patients were victims of traumatic brain injury. There were two patients who had
      suffered malignant Middle Cerebral Artery Infarctions, one patient had a cerebral
      venous thrombosis and one, an intracerebral hematoma. Four patients in this
      cohort died, while five had good outcomes. CONCLUSION: The rationale and role of
      this relatively easy but underutilised procedure are discussed.

PMID- 23133054
TI  - Abdominal scar endometriosis.
AB  - BACKGROUND: Abdominal scar endometriosis is an uncommon pathology. It can occur
      in any abdominal scar, most often after a surgical procedure on the uterus. AIM:
      The purpose of this study is to highlight the potential pitfall in the diagnosis
      of this disease. PATIENTS AND METHODS: This retrospective study reviewed all
      cases of proven abdominal scar endometriosis seen in a 5-year period (2002-2006)
      in our hospital, noting the demographic data of the patients and management. They
      were all treated by the same surgeon and also had histopathological confirmation
      of the lesion. RESULTS: A total of 14 women were treated during this period. They
      were all pre-menopausal. The mean age was 29.1years (range 20 to 42). Presenting
      symptoms included painful 'heaped-up' scars and cyclical pain related to their
      menstrual periods. They were referred to the general surgical clinic with various
      diagnoses such as incisional hernia, granuloma, keloid scar etc. All the patients
      had history of previous surgical procedures on the uterus for various
      indications. Treatment was a wide excision of the lesion with apposition of the
      edges only. Specimens were examined histologically and confirmed to be
      endometriosis. The follow up periods were rather short as the patients stopped to
      attend the hospital. During this period, there was no recurrence or wound break
      down. CONCLUSION: Although scar endometriosis is a rare entity, a good and
      diligent surgical history and a high index of suspicion are the keys for a pre
      operative diagnosis.

PMID- 23133055
TI  - Extra adrenal pheochromocytoma of urinary bladder.
AB  - Pheochromocytoma of urinary bladder is rare disease causing a hypertension,
      palpitation, throbbing headache & hemorrhage induced by voiding. This case is
      reported because of rarity of this disease in urinary bladder.

PMID- 23133056
TI  - An unusual cause of obstructive uropathy: primary retrovesical hydatid cyst.
AB  - The incidence of hydatid disease in genitourinary system is very low and isolated
      involvement in retrovesical region is rare [1-3]. Here is a report of a case of
      retrovesical hydatid cyst leading to obstructive uropathy with successful
      outcome.

PMID- 23133057
TI  - Renal adenocarcinoma presenting as a groin swelling: a case report.
AB  - Renal cell carcinoma (RCC) is known to have myriad presentations due to the
      extremely vascular nature of the organ. RCC are known to metastasize extensively
      to various organs of the body. We report a case of a 70-years-old male who
      presented with multiple inguinal lymph node enlargements which on excision biopsy
      showed metastatic adenocarcinomatous deposit. Search for the primary revealed a
      RCC arising from the left kidney. Inguinal lymph nodal metastasis, an uncommon
      site of distant metastasis in renal neoplasm, as a fi rst clinical sign leading
      to the diagnosis is not yet reported in literature.

PMID- 23133058
TI  - Distal posterior tibial artery pseudoaneurysm after fracture calcaneous.
AB  - Here we report a case of pseudoaneurysm of distal posterior tibial artery
      following closed fracture of calcaneous. Association of pseudoaneurysm of
      posterior tibial artery with fracture of calcaneous is extremely uncommon. It is
      always suggested that pseudoaneurysm be treated by reconstruction, but here we
      present the case treated by ligation, obliteration and excision as it was
      situated distally and the plantar arch circulation was maintained. The purpose of
      this case report is to bring attention to this complication of vascular trauma,
      which may cause delayed symptoms long time after the injury as well as the rare
      incidence of posterior tibial artery involvement with fracture calcaneous.

PMID- 23133059
TI  - Perivascular epithelioid cell tumor (PEComa) of falciform ligament - an extremely
      rare tumor.
AB  - Primary tumor of falciform ligament is exceedingly uncommon. So far, seven cases
      of Perivascular Epithelioid Cell tumor (PECom), a recently described histological
      entity with characteristic perivascular tumor cell arrangement and expression of
      muscle and melanocytic marker by the cells, have been reported in literature.
      Here, we report a case of PEComa of falciform ligament, which presented with a
      huge abdominal lump. Pre-surgical CT scan of abdomen was uninformative regarding
      the nature and organ of origin of the tumor. On laparotomy, it was surprisingly
      found to arise from the falciform ligament, and this was easily removed.
      Histopathological diagnosis confirmed PEComa. There was no recurrence of disease
      after two years of follow up.

PMID- 23133060
TI  - Gross calcification within the prostate gland and its significance and treatment.

PMID- 23133061
TI  - Synchronous esophageal and gastric cancers.

PMID- 23133062
TI  - Ultrasound guided hydrostatic reduction of acute intussusception.

PMID- 23133063
TI  - Empyema management protocol.

PMID- 23133064
TI  - The role of stem cells in neural injury - emerging paradigms.
AB  - Stem cells capable of proliferating along neuronal and glial lines persist in the
      adult central nervous system (CNS). These cells are found pedominantly in the
      subventricular zones and in the hippocampus. The therapeutic potential of both
      endogenous and exogenous stem cells in achieving repair of the injured CNS is
      being explored. Stem cells from embyonal lines, mescnchymal stromal cells and
      neural stem cells are being investigated for their potential role in the
      management of neural loss due to traumatic hypoxic or inflammatory insult.

PMID- 23133065
TI  - Role of alpha blocker therapy in chronic prostatitis/chronic pelvic pain
      syndrome: limited options with promising results.
AB  - Chronic prostatitis / chronic pelvic pain syndrome (NIH-type II and type III
      prostatitis) are common cause of chronic pelvic pain. The exact etiology of these
      entities are unknown. They are associated with varying degree of voiding and
      sexual dysfunction. Consensus regarding treatment of these pain syndromes is
      lacking. Review of literature suggest a therapeutic role of alpha adrenergic
      receptor blockers in the management of NIH-type II and type III prostatitis. A
      trial of alpha-blocker is reasonably inexpensive and appropriate for most
      patients suffering from NIH-type III prostatitis and NIH-type II prostatitis. A
      general consensus is that if a patient agrees to a trial of alpha-blocker therapy
      which subsequently shows a good response then it should be continued for at least
      6 months for a proper therapeutic effect. This review analyses the role of alpha
      blockers in this disease/syndrome; discusses the possible mechanism of action
      through which these drugs provide relief and also highlights some of the
      important trials which have paved way for this particular treatment option in
      this intriguing disease /syndrome.

PMID- 23133066
TI  - Surgical instruments and endoscopes of Susruta, the sage surgeon of ancient
      India.
AB  - Susruta, the great sage surgeon, philosopher and teacher of ancient India,
      practiced around 600 bc. He is renowned all over the world for his contribution
      to surgery in general and plastic surgery in particular especially rhinoplasty.
      But his contribution to endoscopes is not well known to the medical world. His
      contribution to surgical instruments including endoscopes is reviewed here.
      Literature survery was the basis of this study. Susruta samhita [1], the treatise
      compiled by Susruta, various commentaries on it by different authors [2, 3] and
      other related literature are used as primary sources. Susruta belonged to a
      period between 600 and 800 bc. His conception of surgical instruments, the
      description of their quality, methods of manufacture and their usage are very
      unique, as there were no earlier comprehensive descriptions of similar surgical
      instruments by any surgeon, not only in India but also the whole world. Susruta
      was perhaps the first surgeon in the world to describe different types of
      surgical instruments including endoscopes. This is far beyond the imagination of
      any other surgeon at that period of time and obviously he was far ahead of his
      time in this field.

PMID- 23133067
TI  - Acute gallstone pancreatitis: a constant challenge for the surgeon.
AB  - INTRODUCTION: Acute pancreatitis is an inflammation of the pancreas caused by
      autodigestion of the gland by its enzymes. It includes a broad spectrum of
      pancreatic disease, which varies from parenchymal edema to necrosis. The
      objective of the current study was to describe the symptoms of the patients with
      gallstone-associated pancreatitis and to reinforce the opinion that operation,
      within the first 72 hours after the onset of the disease, has many advantages and
      has to be considered as a treatment option when ERCP is not available. METHODS:
      The present retrospective study concerns all patients that were hospitalized in
      Mamatsio Hospital of Kozani during the period between Jan 1, 1997 and Dec 1, 2002
      under the diagnosis of gallstone-associated acute pancreatitis. From the records
      108 cases were identified (43 males and 65 females). The mean age was 62.93 (SD
      15.85 years), ranging from 17 to 91 years. RESULTS: 24 patients (22.22%)
      fulfilled more than 3 of Ranson's criteria. 20 patients (18.52%) presented
      necrotizing pancreatitis. All patients underwent open cholecystectomy and common
      bile duct exploration. Necrosectomy concomitantly with cholecystectomy was
      performed in 7 patients (6.48%). The mean hospitalization was 10.53 days (S.D.
      6.38 days), ranging from 2 to 36 days. The associated mortality reached 5.55% (6
      patients) and no patient died in the operating theater. During the 12-month
      follow-up period, 2 patients (1.85%) developed pancreatic pseudocysts.

PMID- 23133068
TI  - Laparoscopic correction of peritoneal catheter dysfunction.
AB  - PURPOSE: To present our experiences with laparoscopic repair of peritoneal
      catheter dysfunction METHODS: Total of 24 patients with peritoneal catheter
      malfunction were considered for two-port laparoscopic manipulation. Two patients
      with unsuccessful result in the first trial and 3 patients with successful
      peritoneal dialysis results were reoperated because of catheter dysfunction.
      RESULTS: The success rates at the first and second manipulation was 79% and 80%.
      The most frequent cause of catheters dysfunction was migration of catheters out
      of the true pelvis. During the follow up, 8 patients were referred for renal
      transplantation, 8 underwent hemodialysis and 5 continued with normal catheter
      function. The mean longevity of the catheters after laparoscopic correction was
      42 months. One year longevity rate as measured as 79%. CONCLUSION: Laparoscopy is
      the procedure of choice even in recurrent cases, for correction of malfunctioning
      continuous ambulatory peritoneal catheters, because this procedure is the only
      technique that can detects pathologic causes of catheters malfunction and can
      resolve those problems at the same time.

PMID- 23133069
TI  - Eosinophils, mast cells, nerves and ganglion cells in appendicitis.
AB  - INTRODUCTION: Twenty to thirty percent appendices removed from patients with
      suspected appendicitis appear normal on histology. The cause of pain in these
      patients is unknown. The presence of eosinophils and mast cells should be looked
      at skeptically which may explain the cause of pain. The aim was to study the
      eosinophils, mast cells, nerves and ganglions in normal and inflamed appendices.
      MATERIALS AND METHODS: A total of 329 appendices including 192 case of acute
      appendicitis (group A), 94 cases of clinically acute but histologically normal
      appendices (group B), 13 cases of complementary/elective appendicectomies (group
      C) and 30 normal controls from medico-legal autopsies(group D), were studied for
      the presence of eosinophils, mast cells, nerves and ganglia in mucosa, submucosa
      and muscularis propria. Routine haematoxylin and eosin stained sections were used
      for eosinophils, nerves and ganglia and Toludine blue sections for mast cell
      counts. One way ANOVA and logistic regression was used for statistical analysis
      RESULTS: The mean eosinophil and mast cell counts were significantly higher in
      mucosa, submucosa and muscularis propria in Group A and B, when compared to group
      C+D. The number of nerves and ganglion cells were significantly higher in group A
      when compared to groups B and C+D. The correlation between eosinophil and mast
      cell count was not found to be statistically significant. CONCLUSION: A
      significant increase in Eosinophils, mast cells, nerves and ganglion cells was
      seen in acute appendicitis. Increase in eosinophils and mast cells may explain
      the pain in histologicaly normal but clinically suspected acute appendicitis.

PMID- 23133070
TI  - Adult Wilms' tumor masquerading as pyonephrosis: a diagnostic dilemma.
AB  - In the era of modern imaging, modalities like ultrasonography, computed
      tomography and magnetic resonance imaging diagnosis of renal mass lesions has
      become more accurate. Nevertheless, rare cases of renal adenocarcinoma and other
      primary renal tumors have been rarely reported to mimic pyonephrosis, renal
      abscess, perinephric abscess or tuberculosis. We report, for the first time in
      literature, a case of Wilms' tumor mimicking as a case of pyonephrosis. The
      incidence, possible causes and implications of such a misdiagnosis and the
      measures to avoid the same are discussed.

PMID- 23133071
TI  - Central pancreatectomy for neoplasm of mid pancreas - a report of four cases.
AB  - Central pancreatectomy (CP) originally done for pancreatic trauma and focal
      pancreatitis is recently being performed for benign and low grade malignant
      neoplasm of mid pancreas. It offers the advantage of conserving pancreatic tissue
      and preserving gastroduodenal-biliary anatomy, important for maintenance of
      endocrine and exocrine pancreatic function. We reviewed our database between Jan.
      2005 and June 2007. Four patients (2 males and 2 females) in the age range of 12
      to 55 years underwent CP for a mass in the mid pancreas. Two were known diabetic.
      Histology reported solid variant of serous cystadenoma (1), solid pseudopapillary
      tumor (1), focal pancreatitis (1) and ductal adenocarcinoma (1). Postoperatively
      one patient had transient pancreatic fistula which was managed conservatively.
      There was no mortality. On follow-up (7 to 43 months) none of the patients
      required enzyme supplements and diabetes did not worsen. Patient with ductal
      adenocarcinoma progressed within 7 months. CP may be a viable option for mid
      pancreatic lesions of benign or low grade malignant potential.

PMID- 23133072
TI  - Granulomatous mastitis - a diagnostic dilemma.
AB  - Granulomatous lobular mastitis is a rare benign breast disease. It is
      characterized by chronic, non-caseating granulomatous lobulitis. It may be
      misdiagnosed as a carcinoma of the breast and may lead to mastectomy. Diagnostic
      criteria include-A) Granulomatous infl ammation with multinucleated giant cells,
      epithelioid histiocytes. B) It is centered on lobules with minor ductal and
      periductal infl ammation. C) It nearly always follows the pregnancy. A case of
      GLM, which was treated with local excision and postoperative steroid therapy is
      being reported to increase awareness amongst surgeons and pathologist.

PMID- 23133073
TI  - Benign cystic teratoma of mediastinum.
AB  - Benign mediastinal teratoma accounts for 60% of all mediastinal germ cell tumors,
      which in turn account for 15-20% of all anterior mediastinal masses. It is
      frequently associated with compressive effects of surrounding structures. Total
      surgical excision is curative and life saving also. We are presenting a case of
      giant benign cystic mediastinal teratoma which underwent surgical excision but
      long term compressive effect on lungs resulted them to be small in size compared
      to thoracic cavity even six months postoperatively.

PMID- 23133074
TI  - Mesenteric cyst: an unusual presentation.
AB  - A 5-year-old boy presented with the history of a small lower abdominal swelling
      since childhood which increased in size and became painful following a fall.
      Examination revealed a mobile, globular, cystic intraabdominal mass in the lower
      abdomen. Ultrasonography of the abdomen suggested a 7.5 * 5.5 cm cystic lesion,
      separate from the bladder, containing an echogenic mobile mass. Intra venous
      urography excluded any abnormality of the kidneys, ureters and bladder.
      Exploratory laparotomy revealed a sigmoid mesenteric cyst protruding out of one
      of the mesenteric leaves and attached to it by a narrow stalk. The excised cyst
      was found to be thin walled and unilocular. It was internally lined with
      fibrinous exhudate and contained serous fluid and a solid spherical blood clot.
      The child had an uneventful postoperative recovery. Histopathology of the cyst
      wall showed maturing granulation and fibrous tissue with hemosiderin laden
      macrophages and lymphoid aggregates consistent with the diagnosis of a
      lymphagioma with chronic inflammatory changes and evidence of past hemorrhage.

PMID- 23133075
TI  - A rare intramuscular hemangioma - case report.
AB  - Intramuscular hemangiomas are rare, slow growing, angiomatous tumors, generally
      asymptomatic, and rarely presenting with complications. We report a rare case of
      a Hemangioma of the Flexor Digitorum Superficialis in a 13-year-old boy, present
      since birth and with extensive involvement, necessitating excision of the muscle.
      The patient is presently doing well, barring minimal weakness in finger flexion.

PMID- 23133076
TI  - Impacted gall stone ileus, seventeen of them!

PMID- 23133077
TI  - Mucinous cystadenoma of appendix.

PMID- 23133078
TI  - Examination triggered appendicitis: is it a new generation entity?

PMID- 23133079
TI  - From the Editors' desk.

PMID- 23133080
TI  - Surgical gastroenterology in India - the evolution of a revolution: a personal
      perspective.

PMID- 23133081
TI  - Current status of laparoscopic surgery in gastrointestinal malignancies.
AB  - Laparoscopy has become a significant tool in a surgeon's armamentarium since the
      first laparoscopic cholecystectomy in 1989. Oncological surgeons have been slow
      in adopting laparoscopy for fear of inadequate cancer operation and occurrence of
      port site metastasis. Neither of these concerns have stood the test of time.
      Laparoscopy is being used increasingly in oncological surgery both for staging
      and respective surgery. This article outlines the present use of laparoscopy in
      GI cancer surgery.

PMID- 23133082
TI  - Nutritional support in gastrointestinal surgery: an overview.
AB  - Nutritional status is important in determining the outcome of surgical patients.
      This is particularly so in patients undergoing gastrointestinal (GI) surgical
      procedures. It is important for the GI surgeon to be always aware that he has to
      assess the nutritional status of his patient, provide supplementation when
      required and have the means to get enteral and/or parenteral access when
      required. He must have the knowledge to choose the right route and formula for
      nutritional support. This evidence-based review gives an overview of the subject
      with the purpose of increasing awareness about the science of surgical nutrition.

PMID- 23133083
TI  - Intestinal duplication.
AB  - Gastrointestinal duplications are rare but interesting clinical entities. They
      have a varied presentation, with most of them showing up in paediatric
      population. Clinical features may vary from asymptomatic abdominal masses to
      bowel obstruction or perforation. This review traces the embryological origin and
      describes the anatomical types of duplications. An outline of the principles of
      management is described.

PMID- 23133084
TI  - Perspectives of tumour markers in gastrointestinal malignancies - an overview.
AB  - There is an increasing incidence of GI cancers as per the Cancer Registry Data.
      In such a situation, it is essential to evaluate the patient by standard
      investigational tools like clinical examination and endoscopy which help in
      establishing the diagnosis. Determination of tumour markers is useful not only in
      diagnosis and prognosis of cancer but also monitoring of cancer treatment. Tumour
      markers in GI oncology include oncofoetal proteins, hormones, enzymes and cancer
      antigens. Recent advances include application of tumour marker level
      determination combined with newer radiological and functional imaging such as FDG
      PET - CT.

PMID- 23133085
TI  - Mirizzi syndrome.
AB  - Mirizzi syndrome is a complication of long standing cholelithiasis. In this,
      obstruction of the extrahepatic bile duct by stone/s in the Hartman's pouch or
      cystic duct (Mirrizi type I) may erode in to the bile duct forming
      cholecystobiliary fistula (Mirrizi type II). Altered biliary tract anatomy and
      the associated pathology make cholecystectomy, open or laparoscopic, a formidable
      undertaking. Awareness of this entity and its preoperative diagnosis is of
      paramount importance to avoid injury to the bile duct at surgery. Improper
      surgical procedures may lead to long-term stricture formation. The present
      article reviews the available literature on various aspect of this syndrome
      including its pathogenesis, diagnosis and recommended management guidelines.

PMID- 23133086
TI  - Management of massive haemobilia in an Indian hospital.
AB  - INTRODUCTION: Massive haemobilia carries a mortality of 25% in most reports.
      Although previously it was mainly due to road accidents or homicidal attempts it
      is now more often due to iatrogenic trauma like percutaneous liver biopsy and
      biliary drainage. However the management protocol is not established and there
      have been few reports of this serious condition from India. AIM: To review the
      causes of massive haemobilia and outline its management in an Indian hospital.
      PATIENTS AND METHODS: We retrospectively analysed the records of 20 consecutive
      patients with massive haemobilia (blood requirement more than 1400 ml/day)
      admitted to our department over six years from a prospectively maintained
      database. There were 10 males and 10 females who had a mean age of 43 (range 15
      65) years. RESULTS: Haemobilia accounted for 9 percent of patients admitted with
      upper gastrointestinal bleeding who were seen over this period. The commonest
      cause was iatrogenic (11) including laparoscopic cholecystectomy (6), Whipple's
      operation, endoscopic retrograde cholangiography (ERC), percutaneous transhepatic
      cholangiography (PTC), hepatic stone extraction and removal of biliary stent (1
      each). The others had accidental trauma (4), visceral aneurysms (2), biliary
      stones (2) and chronic pancreatitis (1). The commonest clinical presentation was
      massive gastrointestinal bleeding. The dual phase computed tomography (CT) scan
      correctly identified the site of bleeding and other associated conditions in all
      the 11 patients in whom it was done. Conventional angiography was done in 8
      patients with transarterial embolisation (TAE) being attempted in 6 and
      successful in 2 patients. Operations were performed in 18 patients for the
      following indications - failure of angiographic embolisation (6), failure of
      endoscopic sclerotherapy (EST) (1), duodenal erosion (2), portal biliopathy (1),
      haemoperitoneum (1), bile leak (1), pseudocyst (1), liver necrosis (1) and other
      hepatobiliary conditions (4). The surgical procedures to control bleeding were
      ligation of aneurysms (8), repair of the hepatic artery (4), right hepatectomy
      (3), lienorenal shunt, cholecystectomy and under-running of the duodenal papilla
      (1 each). The overall mortality was 4 patients (20 percent). There was no
      mortality in patients with bleeding aneurysms; the mortality being significantly
      higher in patients with non-aneurysmal bleeding (p=0.0049: Fishers' exact test).
      CONCLUSIONS: In our experience haemobilia was usually due to an iatrogenic cause
      with a pseudoaneurysm following a diagnostic or therapeutic intervention(most
      often laparoscopic cholecystectomy) being the commonest aetiology. A dual phase
      CT scan accurately identified the site of bleeding. Angiographic embolisation
      often failed to stop bleeding and mortality was significantly higher in patients
      with non-aneurysmal bleeding. We should perhaps consider early surgery for
      haemobilia once the bleeding site has been localised by CT scan.

PMID- 23133087
TI  - Laparoscopic management of large hiatus hernia with mesh cruroplasty.
AB  - PURPOSE: Laparoscopy has become the standard surgical approach to surgery for
      gastrooesophageal reflux disease (GERD) and hiatal hernia repair with excellent
      long-term results and high patient satisfaction. However several studies have
      shown that hiatal hernia repair, especially large hiatus are associated with high
      recurrence rate. Mesh reinforcement has been proposed for repair of large hiatus
      hernia. The objective of this study was to evaluate the role of mesh cruroplasty
      in management of large hiatus hernia (> 5 cm). METHODS: Between February 2002 to
      December 2007, 73 patients (28 men and 45 women) who underwent laparoscopic
      hiatal hernia repair with mesh cruroplasty were included in our study. Mesh
      reinforcement (cruroplasty) was used for repair of large hiatus hernia (>5 cms
      hernial defect). Mean age was 50.4 years (range 30-72 years). Follow up included
      barium swallow of patients at 3 months and yearly thereafter. RESULTS: Seventy
      three patients underwent mesh cruroplasty for large hiatus hernia. We were able
      to adequately mobilise the oesophagus to achieve an intra-abdominal length of at
      least 3 cm in all patients. Intraoperative complication rate was 8.21% (6/73),
      intraoperative complications included pleural tear, bleeding from splenic capsule
      laceration and short gastric vessels. Postoperative complication rate was 4.1%
      (3/73), which included complete dyspahgia, atelactasis and pneumonia. Mean
      duration of hospitalisation was 3.5 days (range 3-9 days). Five patients (5/73)
      were lost to follow up. Four patients (5.8%) developed recurrence on routine
      follow up. No mesh related complications were noted on long-term follow up
      period. Mean follow up period was 3.2 years (range 5 months-6 years). CONCLUSION:
      Our data supports the use of mesh in hiatal hernia repair, especially in large
      hiatus hernia as it leads to low recurrence rates. Longer follow up and more
      randomised controlled trials are needed to establish laparoscopic mesh
      cruroplasty as standard technique for large hiatal hernia repair.

PMID- 23133088
TI  - Small bowel enterocutaneous fistulae: the merits of early surgery.
AB  - BACKGROUND: The treatment of patients with small bowel enterocutaneous fistulas
      is complex and a challenge for every surgeon. The mortality and morbidity
      associated with only conservative management is often high and expensive because
      most patients cannot afford prolonged parenteral nutrition which itself carries a
      high incidence of complications. Although operations are difficult if performed
      early they may be lifesaving in our situation. The focus of our study was to
      determine whether, in patients with fistulae, early intervention resulted in low
      mortality and morbidity rates and to identify prognostic factors for fistula
      closure and mortality. PATIENTS AND METHODS: Between August 1996 and July 2008 we
      treated 64 consecutive patients with small bowel enterocutaneous fistulae. There
      were 28 females and 36 males patients who had a mean age of 42.4 years. 49 (77%)
      of the fistulae resulted from surgical complications. Our policy was to intervene
      early once the patient was fit for a procedure. RESULTS: In 4 patients (6.2%) the
      fistulae arose from the jejunum and in the remaining 94% from the ileum.
      Octreotide was administered in 49 (77%) patients. To maintain the nutrition of
      the patients enteral feeding was used in 47 (73%) while re-feeding of the
      proximal gut fistula output into the distal stoma was used in 7 patients.
      Spontaneous closure occurred in 10 patients (16%). There were 9 deaths (14%).
      Fifty-two patients (81%) required surgical intervention at some stage. A strong
      relationship was found between their preoperative albumin levels and and
      mortality. CONCLUSION: Aggressive early surgical treatment with the judicious use
      of nutritional support, stoma care, octreotide, and control of sepsis results in
      a low mortality in patients with small intestinal fistulae. Preoperative
      hypoalbuminaemia is an important prognostic variable.

PMID- 23133089
TI  - Management of post dilatation oesophageal perforation: an experience from a
      tertiary centre.
AB  - BACKGROUND: Treatment of oesophageal perforation remains controversial. This
      study shows that native oesophagus should be preserved. Early recognition
      improves survival. AIM: The aim of this study was to evaluate the outcome of
      management of post dilatation oesophageal perforation in a tertiary centre.
      METHODS: Between 1999 and 2007, 35 patients with oesophageal perforation
      following dilatation were treated. Post dilatation corrosive stricture
      perforations constituted the major aetiology. RESULTS: Twenty-four (69%)
      underwent early intervention (< 24 hours) and the remaining 11 (31%) were late
      (>24 hours). The 30-day mortality was found to be 9%, and mean hospital stay was
      14 +/- 14.7 days. Comparing outcomes between early and late groups, statistically
      significant difference was observed, with increased mortality (p=0.001) and
      hospital stay (p=0.001) following late intervention. CONCLUSION: Early
      intervention decreases mortality and hospital stay in oesophageal perforation and
      preservation of oesophagus may be attempted, as native oesophagus is the best
      conduit.

PMID- 23133090
TI  - Role of gastric bypass in patients with unresectable advanced carcinoma of
      stomach.
AB  - CONTEXT: Role of bypass as a palliative surgery for advanced gastric cancer
      remains controversial. AIMS: To determine the role of bypass in advanced gastric
      cancer in comparision to resection as gold standard. DESIGN: Hospital-based
      retrospective outcome as study. METHODS: Patients were divided into three groups:
      group I (gastric resection), group II (bypass) and group III (exploratory
      laparotomy alone). The three groups were analysed for palliation of symptoms,
      operative morbidity and mortality and survival. STATISTICAL ANALYSIS USED: Chi
      square, Fischer, One-way Anova, Unpaired-t, Kaplan-Meier analysis. RESULTS: In
      hospital morbidity was 19.38% (19 patients) for the entire study group. Bypass
      group had a lower morbidity rate as compared to the resection group (p=0.029). In
      hospital mortality rate was 6.12% (6 patients) for the entire study group.
      Mortality rates did not differ between the groups. Patient satisfaction with
      palliation of symptoms was similar between gastric bypass and resection. Gastric
      resection group had significantly better survival (p=0.002) compared to the
      nonresective procedures. However, gastric bypass did not confer any survival
      benefit over exploratory laparotomy (p=0.501). CONCLUSIONS: Gastric bypass can be
      done when resection is not possible as it palliates symptoms on par with
      resection and is associated with low operative morbidity though it does not
      improve the survival outlook of patients.

PMID- 23133091
TI  - Varied presentations of gastrointestinal stromal tumour.
AB  - Gastrointestinal stromal tumours (GIST) are soft tissue tumours arising from the
      mesenchyma in the gastrointestinal tract. These are rare tumours. However, over
      the past few years with the better understanding of the pathogenesis of GIST and
      better imaging facilities, the diagnosis is made more frequently. The
      characteristic diagnostic feature of GIST is the expression of CD34 and receptor
      tyrosine kinase KIT, CD117 by these tumours. The use of tyrosine kinase inhibitor
      imatinib mesylate has led to improved outcome. The presentation of GIST however
      remains non-specific, and varies depending upon the size and the organ of origin.
      We present a series of four cases of GIST with varied presentation.

PMID- 23133092
TI  - Foreign body granulamatous reaction to endoluminal gas in pneumatosis
      intestinalis - a case report.
AB  - Pneumatosis intestinalis is a rare condition occurs in a wide variety of
      patients, some of whom require urgent surgery, while others can be observed with
      resolution of symptoms and radiographic findings. Most often the need for surgery
      is intestinal obstruction. We report a case of pneumatosis intestinalis with an
      abdominal mass causing obstruction. The histological surprise and the rarity of
      the obstruction is highlighted in this case report.

PMID- 23133093
TI  - Tuberculous abdomen presenting as gluteal abscess.
AB  - Tuberculosis (TB) abdomen presenting as gluteal abscess is very rare and
      difficult to diagnose in the absence of high index of suspicion; ruling out the
      possibilities of other diagnosis by means of suitable investigations is the only
      way to arrive at this diagnosis in an immuno-competent patient. We report an
      interesting case of TB abdomen presenting as gluteal abscess in a 27-year-old
      young female patient, who is otherwise hale and healthy.

PMID- 23133094
TI  - Improvised laparoscopic stone picker.
AB  - Laparoscopic cholecystectomy is the treatment of choice for calculus
      cholecystitis. It is frequently complicated by stone spillage and retrieval of
      these stones is a cumbersome process which is frequently complicated by injuries.
      Moreover left over stones frequently leads to complication. We have hereby
      improvised a laparoscopic hand instrument which quickly and easily recovers
      intraabdominal free and scattered gall stones with a loss of little bit of intra
      abdominal CO(2). This stone picker was applied in over 50 cases with successful
      recovery of stones and a mean loss of about 0.1 Lts of carbon dioxide gas.

PMID- 23133095
TI  - John Benjamin Murphy - Pioneer of gastrointestinal anastomosis.
AB  - Surgery as a speciality has reached an advanced refinement today both in terms of
      teaching and technique. With knowledge gained from years of research, teaching is
      now evidence-based. With the illuminating, pioneering work of a few great former
      surgeons, the technique of even complex surgical procedures has been well
      elucidated now. John Benjamin Murphy is one such surgeon to whom the speciality
      of surgery would remain perpetually indebted. His landmark achievements not only
      in gastroenterology but also in urology, orthopaedics, oncoplastic and vascular
      surgery would leave even a hard-core critic marvelling at his genius. Above all,
      Murphy was a dedicated teacher who spent 4 days a week demonstrating procedures
      and lecturing interested surgeons. Herein lies the greatness of the man and a
      tribute highlighting his achievements are in order.

PMID- 23133096
TI  - Malignant masquerade at the hepatic hilum.

PMID- 23133097
TI  - Too bitter to swallow - peroperative conundrum.

PMID- 23133098
TI  - Message from the President of ASI-2009.

PMID- 23133099
TI  - Extended pancreatectomy for pancreatic cancers.
AB  - Pancreatic cancer carries a poor prognosis. A minority of patients are considered
      for surgical excision. Local extension, lymph node metastasis, poor prognosis
      with distal spread and the lack of effectiveness of chemo and radiotherapy, have
      led to a nihilistic approach to this disease. This review outlines the rationale
      for and technique of extended resections in pancreatic cancer.

PMID- 23133100
TI  - Surgical innovation.
AB  - Innovation has been an integral part of the progress of surgery. Technological
      advances have given a different dimension to the intricacies of modern surgery.
      While some innovations have been ground-breaking, others made only a transitory
      impression. This article attempts to distinguish between a true innovation and a
      technical refinement and explores the ethos and socio-economic factors that
      propel surgical innovation. The role of validation and regulation of these
      innovative procedures in producing improved outcomes are also discussed.

PMID- 23133101
TI  - The incidence of soft tissue sarcoma in Dakshina Kannada: study in a District
      Government Hospital.
AB  - BACKGROUND: We present a retrospective study depicting the incidence and outcome
      of soft tissue sarcomas (STSs) in patients admitted in a District Government
      Hospital situated in coastal belt of Southern India for a period of four and a
      half years. The hospital is a district referral centre catering to rural and
      urban poor population of 1,900,000 people. METHODS: Histologically proven soft
      tissue STS patients admitted in Department of General Surgery in District
      Government Wenlock Hospital, Mangalore, from January 2002 to July 2007 were
      included in the study. The incidence, age distribution, gender distribution,
      histological subtypes, site of tumour, and clinical outcome were the parameters
      studied. The above parameters were then compared with Memorial Sloan and
      Kettering Cancer Centre (MSKCC) study. RESULTS: Fifty-one cases of STS were
      reported out of 7674 (0.65%) patients with cancer in the said period. Ninety
      percent belonged to adolescents and adult age group. Liposarcoma (18%) is the
      most common subtype followed by leiomyosarcoma, Ewings' sarcoma. 66.6% originated
      in the extremities and rest being intra-abdominal and retroperitoneal. The age of
      presentation was a decade less than MSKCC study. The alarming yet expected fact
      was 35% of patients came with delayed presentation of the disease and refusal for
      surgery. Thirty-nine percent of patients were treated surgically. CONCLUSION:
      Majority of patients presenting to our institution in advanced stage of the
      disease, indicating ignorance, fear and reluctance for surgery; as well as
      economic constraints, that delay early detection and initiation of proper
      treatment. The incidence appears to be increasing, targeting the younger
      population. There is a definite need to incorporate drug trials in rural set up
      so that patients can be benefited.

PMID- 23133102
TI  - How good is compliance with surgical antibiotic prophylaxis guidelines in a
      tertiary care private hospital in India? A prospective study.
AB  - PURPOSE: There is a need to study compliance with surgical antibiotic prophylaxis
      guidelines in India. METHODS: In this prospective study, 100 consecutive surgical
      procedures performed at a tertiary care private hospital in Mumbai, India were
      observed. The choice of antibiotic, timing and duration of administration were
      recorded and compared to the hospital guidelines. RESULTS: Appropriateness of
      choice of antibiotic was seen in 68%, timing in 89%, dose in 75% and duration in
      63% of cases. Hundred percent compliance to all criteria was observed in 52% of
      cases. The SSI rate was 3.3%. CONCLUSIONS: These compliance rates though
      suboptimal are similar to those reported in world literature. There is an urgent
      need to improve compliance with optimal surgical antibiotic prophylaxis
      guidelines so as to reduce risk of SSI and to prevent resistance and costs
      potentially associated with antibiotic misuse.

PMID- 23133103
TI  - Videothoracoscopic approach to recurrence primary spontaneous pneumothorax: using
      of electrocoagulation in small bulla/blebs.
AB  - OBJECTIVE: To evaluate the effectiveness of electrocoagulation of bullae/blebs
      and apical pleurectomy via videothoracoscopic approach. METHODS: We reviewed 42
      patients who underwent Videoassisted thoracoscopy (VATS) procedure for recurrence
      primary spontaneous pneumothorax (PSP) from 200022006. There were 30 male and 12
      female patients with a median age of 30 years. The percentage of pneumothorax was
      calculated median of 60% (British Thoracic Society Guideline - 2003). Thirty-two
      (76.2%) bullae/blebs were observed with the median diameter of 15 mm (5-30).
      RESULTS: Bulla ablation via cauterisation and apical pleurectomy was performed in
      32 patients. Ten patients underwent only apical pleurectomy/abrasion because in
      this group there was not any either bulla or bleb could be found. The median
      duration of drainage time was 3 days. There was no mortality and complications
      occurred in five (11.9%) patients. Only two (4.76%) recurrence occurred during
      the 52 months (5 to 76) median follow-up period. CONCLUSION: Videothoracoscopic
      bulla ablation with apical pleurectomy is a safe method for recurrence PSP.
      Especially, if the bulla or bleb is smaller than 20 mm the ablation via
      cauterisation reduces the expenses of VATS procedure by avoiding the use of
      stapler devices.

PMID- 23133104
TI  - Sclerotherapy for hydrocele revisited: a prospective randomised study.
AB  - PURPOSE: A prospective randomised trial to study the efficacy and safety of
      hydrocele sclerotherapy with phenol and polidocanol. METHODS: Eighty-six patients
      with unilateral primary vaginal hydroceles were randomised into three groups:
      group 1 (phenol sclerotherapy) - 29 patients, group 2 (polidocanol sclerotherapy)
      - 29 patients and group 3 (operative treatment) - 28 patients. Sclerotherapy was
      performed on outpatient basis using either 5-10 ml of 5% phenol or 2-4 ml of 1%
      polidocanol, while patients in group 3 underwent surgical repair of hydrocele
      (Jaboulay's procedure). Statistical analysis was performed using ANOVA. RESULTS:
      The cure rates in group 1, 2 and 3 were 96.5%, 51.7% and 100%, respectively. The
      pain scores (visual analogue scale) in group 1, 2 and 3 at 1 week and 1 month
      were 14.5 and 1.8; 10.1 and 1.3; 64.0 and 10.6, respectively. There was
      significant difference among the three groups in mean hospital stay (1.8, 1.5 and
      9.7 hours, respectively) and time to work resumption (1.3, 1.1 and 12.7 days,
      respectively). Statistically significant differences in pain scores and
      complications were observed between sclerotherapy and operative groups.
      CONCLUSION: Five percent phenol is a better sclerosant than 1% polidocanol and is
      as efficacious as operative treatment, with lesser morbidity and similar safety
      profile.

PMID- 23133105
TI  - Results of breast conserving surgery in clinical stage I-II breast carcinoma.
AB  - BACKGROUND: The role of breast conserving surgery with radiotherapy is well
      established and has become a widely used procedure in breast cancer. Patient
      selection, a multidisciplinary approach, and expert surgical technique are
      important factors to avoid locoregional recurrence. The aim of this study was to
      analyse the outcomes of patients treated with breast conserving surgery in stage
      I-II breast cancer. METHODS: In this study, the results of 135 breast conserving
      surgery cases are reported. The majority of patients received radiotherapy and
      adjuvant systemic treatment. RESULTS: At a median follow-up period of 54 months,
      5 patients (3.7%) developed locoregional recurrence. The 5 years overall and
      disease-free survival rates were 90% and 84%, respectively. Young age, lymph node
      involvement, and oestrogen receptor negativity were independent predictors for
      overall survival. CONCLUSION: In selected patients, breast conserving surgery
      using good surgical technique in conjunction with radiotherapy can achieve a high
      survival rate with a low locoregional recurrence rate.

PMID- 23133106
TI  - Bone metastases as the initial presentation of carcinoma of gall bladder: a
      rarity.
AB  - Distant metastases are rare form of presentation of carcinoma gall bladder. Bony
      pain as initial presentation is quite unusual. A 50-year-old woman presented with
      the pain in right shoulder. Investigation showed metastatic adenocarcinoma in the
      head of humerus and the primary was found in the gall bladder. She received local
      radiotherapy for bone metastases and undergoing systemic chemotherapy. Carcinoma
      gall bladder is a common abdominal malignancy, mostly presenting in advanced
      stage with abdominal symptoms and obstructive jaundice. In presence of
      metastasis, the management is palliative and role of chemotherapy is limited for
      palliation symptoms.

PMID- 23133107
TI  - An unusual association of gastroduodenal phytobezoar and malrotation of the
      midgut.
AB  - This report describes, for the fi rst time, the association of phytobezoar and
      malrotation of midgut in an 18-month-old male child. He recovered after Ladd's
      operation, enterotomy removal of the bezoar and tapering duodenoplasty. Nowadays
      gastroduodenal phytobezoars are increasingly treated by non-surgical methods such
      as endoscopic disintegration or enzymatic dissolution. The case reported herein
      emphasizes that underlying anatomical malformations must be excluded before
      initiating medical management of gastroduodenal phytobezoars in children.

PMID- 23133108
TI  - Port site metastasis after laparoscopic cholecystectomy.
AB  - We report a case of 62-year-old female, who developed port site metastasis one
      year after undergoing laparoscopic cholecystectomy for calculous cholecystitis.
      This is only second such report in Indian literature.

PMID- 23133109
TI  - Nodular hidradenoma of the breast: A case report with literature review.
AB  - Nodular hidradenoma or clear cell hidradenoma is a rare skin adenexal tumor which
      arises from eccrine sweat glands. Skin adenexal tumors situated in the breast
      parenchyma are still very rare and is one of the differential diagnoses of breast
      tumors. Failure to identify its morphologic features may lead to a mistaken
      diagnosis and over treatment. We report a case of breast lump, in a 40-year-old
      lady, which was diagnosed clinically as a malignant breast lump. Final diagnosis
      of nodular hidradenoma was made only after excision biopsy as fi ne needle
      aspiration cytology was inconclusive.

PMID- 23133110
TI  - Pseudomesenteric cyst.
AB  - Mesenteric cyst and cystic mesenteric tumour are very rare abdominal growth,
      which is generally encountered, in the second decade of life. Pseudomesenteric
      cyst is another variant with traumatic and infective etiology is rare in itself.
      Only 14 cases have been reported previously in the Japanese literature. Emergency
      operation was performed in only 3 patients. The etiology of the pseudocyst
      manifested by acute abdomen was unknown [1]. A case of pseudomesenteric cyst
      presented in the emergency with acute abdomen is reported here.

PMID- 23133111
TI  - Leiomyosarcoma of the inferior vena cava (IVC).

PMID- 23133112
TI  - Giant breast hamartoma.

PMID- 23133113
TI  - Pre peritoneal mesh hernioplasty for incisional hernias.

PMID- 23133114
TI  - Surgical instruments and endoscopes of Sus(h)ruta, the sage surgeon of ancient
      India. By K. Natarajan.

PMID- 23133116
TI  - A prospective study of nutritional status of hospitalised patients in urban
      corporate set up.
AB  - Malnutrition is quite common in hospitalised patients, with most studies
      indicating a prevalence of 20-62%. It is associated with length of stay and
      morbidity in developed countries. This study was performed to identify
      nutritional status of hospitalised patients in urban corporate setting by using
      primarily, the Mini Nutritional Assessment tool. This is a prospective study
      conducted in an urban tertiary care centre. 304 consecutive patients admitted to
      the hospital were studied, between the dates of July 2007 and September 2007. The
      study included the measurement of anthropometrics, global evaluation, dietary
      habits and subjective assessment score. Serum albumin level was used to assess
      visceral protein status. The study excluded Obstetrics & Gynaecology, paediatric
      and critical care cases. Out of the 304 patients, Females 41.55% and Male 42.55%
      were over nourished. Medical patients were more malnourished and at risk of
      malnutrition (15.08% and 70.85%) when compared to surgical patients (12.38% and
      60.95%) respectively. This study shows that in an urban setting, the risk of
      malnutrition (overweight & underweight) is very real. Clinicians have to note
      that malnutrition has a direct impact on the outcome of treatment.

PMID- 23133117
TI  - The incremental value of dual modality PET/CT imaging over PET imaging alone in
      advanced colorectal cancer.
AB  - BACKGROUND: (18)Fluoro-2-Deoxy Glucose (18 FDG) positron emission tomography
      (PET) impacts upon the management of recurrent colorectal cancer (CRC) but is
      limited by anatomical localisation. The development of integrated positron
      emission and computerised tomography (PET/CT) yields high anatomical resolution
      combined with the PET data. We evaluate the added value of PET/CT over PET alone.
      METHOD: Thirty-one consecutive patients had PET/CT for suspected recurrent CRC.
      Two blinded observers (A and B) reported images from PET alone and from
      integrated PET/CT. Lesion detection, lesion localisation, diagnostic certainty
      and impact on surgical management was assessed for each data set and then
      compared. The minimum clinical follow up was for 8 months (median 9.6 months) and
      7 patients had histological confirmation of diagnosis. RESULTS: Compared to PET
      alone, PET/CT the percentage of lesions accurately localised increased from 96%
      to 99% for observer A and 86% to 99% for Observer B. PET/CT increased the number
      of lesions reported as definitely abnormal or normal from 78% to 95% for Observer
      A and from 72% to 94% for Observer B. Surgical management was changed in 6
      patients (19%). Inter-observer variability was reduced with PET/CT. CONCLUSION:
      PET/CT improves the accuracy of reporting in recurrent colorectal cancer and
      influences surgical management in a significant proportion of patients when
      compared to PET only imaging.

PMID- 23133118
TI  - Detection of human papilloma virus 16 and 18 DNA sequences by southern blot
      hybridization in oral leukoplakia and squamous cell carcinoma.
AB  - BACKGROUND: The etiopathological role of human papilloma virus (HPV) in the
      causation of oral cancer is till a subject of speculation. METHODS: We used the
      technique of Southern blot hybridization to detect the presence of HPV types 16 &
      18 in biopsy specimens from oral cancer and leukoplakia patients as well as
      normal oral mucosal biopsies. RESULTS: The prevalence of either HPV type 16 or 18
      was found in 64.5% (29/45) of oral cancer, 40%(12/30) of leukoplakia and
      20%(9/45) of normal oral mucosal biopsies. No association could be demonstrated
      between tobacco usage habits or a history of genital warts with HPV prevalence.
      CONCLUSION: A significant finding was that none of the oral cancer patients were
      negative for both: a history of tobacco usage as well as presence of HPV
      infection, on Southern blot hybridization.

PMID- 23133119
TI  - The effect of Kombucha on post-operative intra-abdominal adhesion formation in
      rats.
AB  - BACKGROUND: Peritoneal adhesions are fibrous bands of tissues formed between
      organs that are normally separated and/or between organs and the internal body
      wall after peritoneal injury. The aim of the study was to investigate the effect
      of intra-peritoneal administration of Kombucha on intra-peritoneal adhesions.
      MATERIALS AND METHODS: Eighty Wistar rats were subjected to standardized lesion
      by scraping model and were randomly divided into two groups. Group I received no
      treatment, and Group II received 15 ml of Kombucha solution intra-peritoneally.
      On the post-operative 14th day adhesion intensity score, inflammatory cell
      reaction and number of adhesion bands were determined. RESULTS: In the control
      group, there were no rats with grade 0 and I adhesions. In the group II, there
      were 26 rats (78.8%) with grade 0-2 adhesions. Adhesion intensity was
      significantly less in group II (P<0.0001). Number of adhesion bands was
      significantly less in group II (P<0.001). CONCLUSION: It was concluded that intra
      peritoneal administration of Kombucha might be useful for preventing peritoneal
      adhesions.

PMID- 23133120
TI  - Has experience changed the scenario in laparoscopic adrenalectomy?
AB  - BACKGROUND: Laparoscopic adrenalectomy (LA) is a relatively uncommon operation
      performed by surgeons with a specific interest in endocrine surgery as well as
      advanced laparoscopic surgery. LA is technically difficult and it is recommended
      to tackle small glands first till adequate experience is reached [1]. A minimum
      of 30 cases are required to master the technique [2]. The present study reviews
      data of 60 laparoscopic adrenalectomies comparing the later results with the
      first 30 cases. MATERIAL AND METHODS: Starting 2001, patients diagnosed to have
      adrenal disorders were subjected to laparoscopic approach in a graded manner. A
      database was maintained with respect to age, sex, duration of symptoms, co-morbid
      conditions, diagnosis, size of tumor, weight of tumor, blood loss, duration of
      surgery, conversion to open, in-hospital stay, referral pattern, morbidity (both
      early and late) and mortality. The database was divided into two groups. First 30
      patients constituted Group A, Group B constituted the next 30 adrenalectomies and
      deviation in the two was noted. Statistical analysis was performed to determine
      the importance of deviation of factors. RESULTS: Sixty adrenalectomies were
      performed in 49 patients (11 being bilateral) between February 2001 and July
      2008. Age group varied from 12-54 years with mean of 30.73 years, Twenty four
      were males. Thirty-one right and 29 left LA were performed. The comparison of
      factors in relation to the two groups (Group A and B respectively) revealed an
      increase in number of adrenalectomies performed (0.4 v/s 0.76) in relation to
      timeline, increased incidence of pheochromocytoma (6 v/s 18) and incidentalomas
      (zero v/s 8), larger tumor size (4.17 cm v/s 6.6 cm), comparable blood loss (72
      cc v/s 98.3 cc) and duration of surgery (122 min v/s 112 min), increased
      conversion to open surgery (1 v/s 6) leading to increased in-hospital stay (2.8
      days v/s 3.37 days) but a comparable morbidity (2 v/s 1) and no mortality.
      CONCLUSION: Though technically difficult, with increasing experience and focused
      approach, laparoscopic skills in adrenalectomy improves. The spectrum of
      indications broadens, thus making laparoscopic interventions for vascular and
      large adrenal glands safe and patient friendly.

PMID- 23133121
TI  - Chronic groin pain following lichtenstein mesh hernioplasty for inguinal hernia.
      Is it a myth?
AB  - BACKGROUND: The Lichtenstein mesh hernioplasty is currently the most popular
      operative technique for open repair of inguinal hernia. The incidence of chronic
      groin pain (CGP) following this procedure is reported to be high. However, since
      our experience did not support this observation, this study was undertaken at our
      centre, to assess the incidence of CGP following Lichtenstein mesh hernioplasty.
      METHODS: A prospective study was conducted on all patients undergoing elective
      hernia repair at a tertiary care teaching hospital. The patients underwent
      Lichtenstein mesh hernioplasty and were followed up for the primary outcome
      measures of development of recurrence and Chronic Groin Pain. RESULTS: A total of
      470 patients were enrolled for the study. Out of these 16 patients never reported
      for follow up after discharge from hospital. The remaining 454 patients with 510
      primary inguinal hernias were included in the study. Of these 449 patients were
      male and 5 were female. The mean follow-up period was 14 months (range - six
      months to twenty four months). One patient had recurrence of hernia and CGP was
      reported in four patients. In all four patients CGP was mild and was well
      controlled with oral NSAIDS used on SOS basis. CONCLUSION: The incidence of CGP
      in our study is 0.78% for the number of operated hernias. This is not only
      considerably less than what is generally reported but is also less disabling.

PMID- 23133122
TI  - Urethral fistula following circumcision: salvaged by buccal mucosa graft
      urethroplasty.
AB  - Fistula following circumcision and at times accompanied by disfigurement of the
      glans penis is a common problem in our country, where a large number of
      circumcision is performed by untrained professionals. These complications may
      have profound negative psychological impact on the growing child. Herein, we
      report the successful closure of such fistula using buccal mucosa, which occurred
      following circumcision (for phimosis) in a 15 year old boy. This resulted in the
      disfigurement of the glans penis with a distal urethral fistula. The fistula was
      managed by dorsal onlay buccal mucosa graft urethroplasty (BMGU). The patient has
      excellent cosmesis at 6 months followup with a good urinary stream. This
      technique can give better results than those, where skin grafts or local flaps
      are used for fistula closure. BMGU is a versatile technique with good long term
      results. The cosmesis and functional results are satisfactory and help in
      improving the self esteem and sexual function in the years to come.

PMID- 23133123
TI  - Spontaneous perforation of common bile duct: a rare complication of
      choledocholithiasis.
AB  - A 35-year-old female presented with 48 hrs history of severe upper abdominal pain
      and abdominal distension. The patient was suffering from intermittent episodes of
      colicky upper abdominal pain and spiky fever with chill and rigor in association
      with yellowish discoloration of eyes and urine for last 3 months. On examination
      the lady was dehydrated, icteric, febrile and was having tachycardia and
      hypotension. Abdominal examination indicated features of generalized peritonitis.
      Hematological profile suggested neutrophilic leukocytosis, blood biochemistry
      suggested conjugated hyperbilirubinemia, raised alkaline phosphatase and
      transaminases. Skiagram of the abdomen showed ground glass opacity without any
      free gas under the diaphragm. Ultrasonography and contrast enhanced CT scan of
      the abdomen revealed multiple calculi within a distended, thick walled gall
      bladder, dilated common bile duct (CBD) with a 12.8 mm stone impacted at its
      lower end and free fluid in the lesser sac and rest of the peritoneal cavity.
      Diagnostic abdominal paracentasis showed heavily bile stained fluid. Exploration
      done for generalized biliary peritonitis with sepsis, revealed erosion at the
      posterior aspect of the retro-duodenal CBD over the site of the impacted stone.
      She underwent cholecystectomy, choledocholithotomy through a supra-duodenal
      choledochotomy, and T-tube drainage of the CBD. She made a slow but steady post
      operative recovery and was discharged from the hospital after 22 days in
      favorable conditions.

PMID- 23133124
TI  - Spontaneous aseptic pneumoperitoneum.
AB  - Pneumoperitoneum indicates the need for urgent laparotomy. But under certain
      clinical situations like, patient on ventilatory support should arouse the
      suspicion of supradiaphragmatic source of pneumoperitoneum. Supradiaphragmatic
      causes account for 10%. This article describes two patients, both on ventilatory
      support in the intensive care unit. Failure to recognize spontaneous aseptic
      pneumoperitoneum can result in unnecessary laparotomy with its risks. Hence under
      relevant circumstances, non-surgical causes of pneumopreitoneum should be
      excluded.

PMID- 23133125
TI  - von Meyenburg's complex in a patient with primary malignancy: role of MRI.
AB  - von Meyenburg's complexes are benign liver malformations histologically
      constituting cystic dilatations of the bile ducts, surrounded by abundant fibrous
      stroma. Appearance of these lesions on MRI is characteristic and a fine needle
      aspiration or biopsy can be avoided and judicious management planned. We report a
      case of esophageal carcinoma who had suspicious lesions in the liver on CT scan,
      which after MRI were confirmed as biliary hamartomas.

PMID- 23133126
TI  - Gall bladder carcinoma presenting as multiple cavitary pulmonary metastases - a
      rare event.
AB  - Carcinoma of the gall bladder is the commonest malignancy of the biliary tract.
      It is either detected incidentally during routine imaging or presents as lump in
      right hypochondrium or with signs of jaundice. Rarely, it may present with
      multiple cavitary metastatic lesions in the pulmonary parenchyma. The authors,
      report such a rare case of gall bladder carcinoma that presented with extensive,
      bilateral pulmonary cavitary metastases with no evidence of any nodal disease and
      where the diagnosis was delayed due to this rare presentation.

PMID- 23133127
TI  - Jejunal diverticula - a rare cause of intestinal perforation.
AB  - Jejunal diverticuli is a extremely rare entity. We report a case of jejunal
      diverticulum as a cause of perforation peritonitis, which has been managed by
      resection anastomosis. This study is important from the perspective that clear
      cut guidelines for managment of jejunal perforation are not available in
      litreture.

PMID- 23133128
TI  - Primary pleural hydatid cyst.

PMID- 23133129
TI  - Bizzare appearance of gluteal sinus on sinogram.

PMID- 23133130
TI  - Evaluation of negative appendicectomy rate in cases of suspected acute
      appendicitis and to study the usefulness of ultrasonography in improving the
      diagnostic accuracy.

PMID- 23133131
TI  - Surgical site infections in any hospital: the true facts.

PMID- 23133132
TI  - Perineal hernia, another incisional hernia?
AB  - A secondary perineal hernia is a type of incisional hernia of the pelvic floor,
      occurring after pelvic surgery such as abdominoperineal excision of the rectum
      and pelvic exenteration. Our aim is to review the available literature on the
      subject. This report reviews a recently repaired case, followed by a review of
      the available literature on the presenting condition, concentrating on approaches
      and methods of repair. Perineal hernias are uncommon, and not many surgeons face
      them. It is not known if and how these hernias could be prevented. The method and
      approach of repair should probably be individualized, but we believe that the use
      of a mesh is important in the repair of such hernias because of the significant
      tissue defect prevailing in most of the cases, in addition to the unhealthy
      tissues related to the use of radiotherapy. The laparoscopic approach has been
      recently utilized and its use is expected to increase.

PMID- 23133133
TI  - Varicose veins: clinical presentation and surgical management.
AB  - BACKGROUND: Varicose vein is a common surgical problem. We studied clinical
      presentation of varicose veins and its surgical treatment. MATERIAL AND METHODS:
      All patients with varicose veins presented to our hospital were included in the
      study. All patients in our study were assessed by clinico etiological Anatomical
      and pathological (CEAP) classification. Diagnosis was further confirmed by Duplex
      ultrasonography RESULTS: Surgery was prefered for 34 out of 40 patients.
      Remaining 6 patients were treated conservatively because 3 patients were pregnant
      and 3 had deep vein thrombosis (DVT). We have used Trendelenburg's operation with
      stripping in 30 out of 34 cases. We find this method to be satisfactory.
      CONCLUSION: Meticulous clinical examination and surgical technique followed by
      closely monitored post operative management is required to reduce morbidity of
      varicose veins. Trendelenburg's operation with subfascial ligation has given good
      results in our set up.

PMID- 23133134
TI  - Amniotic stem cells repair ureteric defect: a study to evaluate the feasibility
      of amniotic membrane as a graft in surgical reconstruction.
AB  - BACKGROUND: Amniotic membrane is considered a promising procedure as a graft in
      the field of ophthalmology and skin reconstruction. It has been shown to decrease
      inflammation, fibrosis, elicit no host immune reaction and also has antibiotic
      actions. AIM: Recently, the amnion has been shown to contain cells capable of
      plasticity. Therefore, we felt its application could be extended to include
      surgical reconstruction. METHODS: We used ureteric reconstruction to study the
      feasibility of the amnion as a graft in these situations. We induced different
      degrees of injury in the ureter of dogs and reconstructed the defect with
      amniotic membrane. In addition, we also studied the effects of supplying the
      graft with a source of blood supply. RESULTS: The subjects were sacrificed after
      6 weeks and histopathological examination showed impressive repair of the defect.
      CONCLUSION: The post reconstruction complications seen with present grafts were
      not seen with amniotic membrane. Therefore, amniotic membrane has produced
      noteworthy results and its potential should be further evaluated in order to be
      used as a cheap, readily available source of graft for the various surgical
      reconstruction procedures.

PMID- 23133135
TI  - An ideal suture for midline abdominal closure?
AB  - BACKGROUND: Within the last decade the customary trend of using non absorbable
      sutures has changed, with numerous studies and meta-analyses advocating the use
      of slowly absorbable sutures, claiming comparable wound strength with
      significantly lower incidence of wound complications. It was the objective of
      this randomized clinical trial to compare two universally accepted suture
      materials, the non-absorbable Nylon and the slowly absorbable Polydioxanone for
      midline abdominal closure in the Indian context. METHOD: 64 patients undergoing
      midline laparotomy were allocated, using block randomization, to mass closure of
      the abdominal wall with continuous polyamide (34 patients) or continuous
      polydioxanone (30 patients). RESULTS: There was an alarmingly higher incidence of
      wound dehiscence in the PDS group requiring secondary suturing (Nylon 0; PDS 5).
      Mid-way through the trial, an interim analysis was performed which revealed an
      unacceptably high incidence of wound dehiscence in the PDS group. This
      necessitated a premature curtailment of the study. There was, however, a
      statistically significantly higher incidence of scar pain in the Nylon group
      (Nylon 9; PDS 1). CONCLUSION: There is a need for a study with larger series, and
      PDS as a choice of suture for midline wound closure cannot be recommended.

PMID- 23133136
TI  - Trauma care - a participant observer study of trauma centers at Delhi, Lucknow
      and Mumbai.
AB  - BACKGROUND: Trained doctors and para-medical personnel in accident and emergency
      services are scant in India. Teaching and training in trauma and emergency
      medical system (EMS) as a specialty accredited by the Medical Council of India is
      yet to be started as a postgraduate medical education program. The MI and CMO
      (casualty medical officer) rooms at military and civilian hospitals in India that
      practice triage, first-aid, medico-legal formalities, reference and organize
      transport to respective departments leads to undue delays and lack
      multidisciplinary approach. Comprehensive trauma and emergency infrastructure
      were created only at a few cities and none in the rural areas of India in last
      few years. AIM: To study the infrastructure, human resource allocation, working,
      future plans and vision of the established trauma centers at the 3 capital cities
      of India - Delhi (2 centres), Lucknow and Mumbai. SETTING AND DESIGN: Participant
      observer structured open ended qualitative research by 7 days direct observation
      of the facilities and working of above trauma centers. MATERIAL AND METHODS:
      Information on, 1. Infrastructure; space and building, operating, ventilator, and
      diagnostic and blood bank facilities, finance and costs and pre-hospital care
      infrastructure, 2. Human resource; consultant and resident doctors, para-medical
      staff and specialists and 3. Work style; first responder, type of patients
      undertaken, burn management, surgical management and referral system, follow up
      patient management, social support, bereavement and postmortem services were
      recorded on a pre-structured open ended instrument interviewing the officials,
      staff and by direct observation. Data were compressed, peer-analyzed as for
      qualitative research and presented in explicit tables. RESULTS: Union and state
      governments of Delhi, Maharashtra and Uttar Pradesh have spent heavily to create
      trauma and emergency infrastructure in their capital cities. Mostly general and
      orthopedics surgeons with their resident staff were managing the facilities.
      Comprehensively trained accident and emergency (AandE) personnel were not
      available at any of the centers. Expert management of cardiac peri-arrest
      arrhythmias, peripheral and microvascular repair were occasionally available.
      Maxillo-facial, dental and prosthodontic facilities, evenomation grading and
      treatment of poisoning - anti venom were not integrated. Ventilators,
      anesthetist, neuro and plastic surgeons were available on call for emergency care
      at all the 4 centers. Emergency diagnostic radiology (X-ray, CT scan, and
      ultrasound) and pathology were available at all the 4 centers. On the spot blood
      bank and component blood therapy was available only at the Delhi centers. Pre
      hospital care, though envisioned by the officials, was lacking. Comprehensively
      trained senior A and E personnel as first responders were unavailable. Double
      barrier nursing for burn victims was not witnessed. Laparoscopic and fibreoptic
      endoscopic emergency procedures were also available only at Delhi. Delay in
      treatment on account of incomplete medico-legal formalities was not seen. Social
      and legal assistance, bereavement service and cold room for dead body were
      universally absent. Free treatment at Delhi and partial financial support at
      Lucknow were available for poor and destitute. CONCLUSION: Though a late start,
      evolution of trauma services was observed and huge infrastructure for trauma have
      come up at Delhi and Lucknow. Postgraduate accreditation in Trauma and EMS and
      creation of National Injury Control Program must be mandated to improve trauma
      care in India. Integration of medical, non traumatic surgical and pediatric
      emergency along with pre-hospital care is recommended.

PMID- 23133137
TI  - Laparoscopic appendicectomy versus open appendicectomy: a comparative study of
      clinical outcome and cost analysis - Institutional experience.
AB  - BACKGROUND: Laparoscopic appendicetomy had not gained importance against open
      appendicectomy and it remains controversial in Indian perspective. AIM: Compare
      the clinical outcome and cost effectiveness of Laparoscopic Appendicectomy (LA)
      versus Open Appendicectomy (OA). METHODS: A prospective study for a period of 21
      months from Oct. 2005 to June 2007, 249 patients underwent appendicectomy and 200
      patients were included in the study. 114 underwent Open appendicectomy and 86
      underwent laparoscopic appendicectomy. Duration of surgery, postoperative
      complications, postoperative hospital stay, postoperative pain and requirement of
      analgesia, resumption of oral feeds, cost of hospital stay and return to normal
      activities was compared and noted. RESULT: Laparoscopic appendicectomy was better
      than open appendiectomy with respect to the wound infection rate, early
      resumption of oral feeds, postoperative pain, lesser use of analgesics,
      postoperative hospital stay (3.13 days after LA, 4.36 days after OA, P < 0.0001)
      and return to normal activities (LA group to OA group; 13.86 days to 19.44 days
      P< 0.0001). Although above mentioned advantages were at the cost of slightly
      increased duration of surgery (58.29 min in OA group to 74.13 min in LA group P <
      0.0001HS) and cost of surgery {LA: OA Rs.4225.81: Rs.5560.92 (P <0.0001)}.
      CONCLUSION: Laparoscopic appendicectomy was better than open appendiectomy with
      respect to wound infection rate, early resumption of oral feeds, postoperative
      pain, lesser use of analgesics, postoperative hospital stay and return to normal
      activities. Although above mentioned advantages were at the cost of slightly
      increased duration of surgery and cost of surgery.

PMID- 23133138
TI  - Social consequences and ethical considerations of postoperative complications of
      surgery.
AB  - A certain percent of patients undergoing operative treatment would always run
      into complications following surgery. With millions of surgeries being performed
      every day, world over, the number of such patients is indeed quite high and their
      predicament needs to be appreciated by the surgical fraternity. One of the
      natural consequences of occurrence of a complication is prolongation of hospital
      stay in most circumstances. This also means increased financial burden for the
      family. There are many other implications involving these patients and these also
      affect the society as well. In our country no support systems exist for helping
      such patients either financially or socially, inspite of the fact that they are
      in difficulty. The hardship they are made to face remains unrecognized and even
      unappreciated most of the times by all concerned. Invariably they are left to
      suffer on their own. The present communication makes an effort to highlight this
      aspect of surgical complications, and the adverse effects, occurrence of such
      complications have on the individual, his/ her family and the society as a whole.
      An attempt has also been made to draw the attention of surgical fraternity to
      these happenings with a suggestion that one needs to react to a situation which
      is largely a creation of our own. As a surgeon, one ought to take this as a
      challenge to one's professional capabilities and expertise, and make active
      efforts to perform routine as well as difficult surgery with no or minimum
      possible complication rates. And if an unfortunate patient does run into
      difficulty, the surgeon must play a positive role to minimize sufferings and to
      rehabilitate him/her back into the society.

PMID- 23133139
TI  - Ureterocystoplasty: a novel approach to augment small capacity urinary bladder in
      adults.
AB  - Ureterocystoplasty is a novel operation well suited for patients having small
      capacity urinary bladder with unilateral poorly functioning kidney and
      megaureter. The megaureter is detubularized and used for urinary bladder
      augmentation. The ureter lining has advantage of being non-secretory and free
      from the metabolic complications of enterocystoplasty. This operation is mainly
      done in children. This is one of the very few from the Asian subcontinent which
      describes the short term results of ureterocystoplasty in an adult patient. We
      report a case wherein ureterocystoplasty was performed in an 18-year male
      presented with a small capacity neurogenic bladder with a grossly dilated and
      tortuous left ureter and a non-functioning left kidney. Left ureter was
      detubularized and used for augmentation after left nephrectomy. Blood supply to
      the left ureter was preserved during the dissection. After the operation, the
      bladder capacity increased adequately and he is doing well at a followup of 1
      year. Ureterocystoplasty works well in the adult patients also and the bladder
      capacity increases adequately following this procedure.

PMID- 23133140
TI  - Large mucocele involving the ventral surface of tongue in a new born: rare
      occurrence.
AB  - This report describes a case of new born baby with large swelling involving the
      ventral surface of the tongue. Antenatal history was not significant. The
      swelling was causing difficulty in breathing and deglutition. The swelling was
      excised completely. Histological report was suggestive of intravasation cyst.

PMID- 23133141
TI  - An unusual cause of haematuria.
AB  - We report an unusual cause of haematuria in a young male patient due to leech in
      urinary bladder. The patient presented with undiagnosed haematuria of 12 days
      duration. Sonography is a safe and noninvasive procedure for diagnosis. Most of
      the leeches are micturated out spontaneously.

PMID- 23133142
TI  - Subtotal colectomy for intestinal Behcet's disease: a histopathological surprise.
AB  - A 40-year-old male who was diagnosed to be having ileocaecal tuberculosis by
      colonoscopy elsewhere was put on antitubercular treatment. Despite therapy over
      three months patient had recurrent bouts of lower abdominal pain and was admitted
      repeatedly with features of subacute intestinal obstruction. CT- abdomen revealed
      concentric large bowel thickening at multiple sites with features of stenosing
      lesions. Patient underwent an exploratory laparotomy and subtotal colectomy was
      done for the diseased large bowel. Post operative histopathological examination
      revealed it to be Behcet's disease. We report a rare case of intestinal Behcet's
      disease requiring subtotal colectomy.

PMID- 23133143
TI  - Recurrent solitary hydatid cyst of the subcutaneous tissue.
AB  - A 28-year-old male patient presented with a recurrent swelling in the left
      lateral chest wall just below the left axilla since seven years. Patient was
      operated for the same swelling eight years back and its biopsy report showed
      hydatid cyst. Patient had not taken any antihelminthic post operatively. Based on
      this, diagnosis of recurrent subcutaneous hydatid cyst was made and total
      cystectomy was done. Post operatively patient was started on albendazole. On
      follow up of one year there is no recurrence. Hydatid cyst is caused by the
      larval stage of Echinococcus. Four species of the Echinococcus tapeworm can
      produce infection in humans. E. granulosus and E. multilocularis are the most
      common, causing cystic and alveolar echinococcosis respectively, while E. vogeli
      and E. oligarthrus have rarely been associated with human infection. Hydatid cyst
      of the subcutaneous is extremely rare. This case report highlights the rare
      location of the hydatid cyst as well its recurrence in rare location.

PMID- 23133144
TI  - Gallstone ileus.

PMID- 23133145
TI  - Retroperitoneal ancient schwannoma.

PMID- 23133146
TI  - A case of congenital diaphragmatic adult hernia presenting as acute intestinal
      obstruction.

PMID- 23133148
TI  - Palliation for "advanced" gastric cancer.

PMID- 23133147
TI  - Continuing medical education programmes.

PMID- 23133149
TI  - Responsible writing.

PMID- 23133150
TI  - Stem cell therapy for critical limb ischaemia - a review.
AB  - Critical limb ischaemia is an intractable condition associated with high levels
      of amputation, leading to a low quality of life and increased morbidity and
      mortality. It is often not treatable by standard therapeutic modalities.
      Neoangiogenesis has been proposed as a novel method of treatment of such
      patients. Vascular endothelial growth factor (VEGF) and cytokine fibroblast
      growth factor (FGF-1) have been shown to elicit neoangiogenesis. Stem cells are
      progenitor cells which can differentiate in vivo into different types of cells.
      Mesenchymal stem cells (MSCs) are a type of adult stem cells which have an
      immunomodulatory effect. Stem cell therapy has been used in animal studies to
      improve limb vascularity in rat and rabbit models. Several clinical studies have
      also validated their use for critical limb ischaemia. However many issues are
      still unresolved. These include the dosage, delivery and safety issues in
      relation to stem cell therapy. However stem cells are likely to be an important
      therapeutic modality to treat critical limb ischaemia in the near future.

PMID- 23133151
TI  - Principles of physics in surgery: the laws of flow dynamics physics for surgeons 
      Part 1.
AB  - In the field of medicine and surgery many principles of physics find numerous
      applications. In this article we have summarized some prominent applications of
      the laws of fluid mechanics and hydrodynamics in surgery. Poiseuille's law sets
      the limits of isovolaemic haemodilution, enumerates limiting factors during fluid
      resuscitation and is a guiding principle in surgery for vascular stenoses. The
      equation of continuity finds use in non-invasive measurement of blood flow.
      Bernoulli's theorem explains the formation of post-stenotic dilatation. Reynolds
      number explains the origin of murmurs, haemolysis and airflow disturbances.
      Various forms of oxygen therapy are a direct application of the gas laws. Doppler
      effect is used in ultrasonography to find the direction and velocity of blood
      flow. In this first part of a series of articles we describe some applications of
      the laws of hydrodynamics governing the flow of blood and other body fluids.

PMID- 23133152
TI  - Agenesis of gallbladder - our experience and a review of literature.
AB  - BACKGROUND: Agenesis of gallbladder is a rare congenital anomaly. Variable
      diagnostic approaches, perioperative management strategies and postoperative
      follow up protocols provide a dilemma to its correct diagnosis and management.
      METHODS: We hereby present five patients with agenesis of gallbladder encountered
      in our institution between 1992 to 2008. Four out of five patients had symptoms
      suggestive of gallstones including upper abdominal pain and acid dyspepsia, which
      were further substantiated by ultrasound reports showing shrunken contracted
      gallbladder with calculi. RESULTS: On laparoscopy the gallbladder was absent in
      all five patients leading to conversion to laparotomy in the initial three
      patients. With increasing experience, the next two patients were diagnosed
      conclusively by laparoscopy to have agenesis of gallbladder, without the need for
      conversion which was further confirmed by post operative imaging studies.
      CONCLUSION: Gallbladder agenesis is rarely encountered in clinical practice. With
      increased experience in laparoscopy, the condition no longer mandates conversion
      to laparotomy for confirmation of diagnosis. Symptomatic improvement occurs in
      all patients following surgical intervention.

PMID- 23133153
TI  - Enteral glutamine supplementation reducing infectious morbidity in burns
      patients: a randomised controlled trial.
AB  - PURPOSE: Enteral glutamine supplements have been shown to reduce infectious
      morbidity in trauma patients, but their effect on patients with burns is not
      completely studied. The objective of this study was to measure the impact of
      enteral glutamine supplementation on infectious morbidity and in turn, the
      hospital-stay in patients with burns. METHODS: Thirty patients with burns were
      randomly divided into two groups with 15 patients in each, the study (glutamine
      supplemented) and control group. Patients were randomised to receive either
      isonitrogenous mixture without glutamine or isonitrogenous mixture with glutamine
      until complete healing of the burn wound occurred. Incidence of positive blood
      culture, wound culture, total leucocyte count, hospital-stay and mortality was
      recorded. RESULTS: The results showed that the incidence of positive blood
      culture was considerably reduced in the study group (0.20+/-0.41) vs. control
      (0.73+/-0.96; p = 0.065). The incidence of positive wound culture was
      significantly reduced in the study group (1.00 +/- 1.25) vs. control (3.53 +/-
      2.47; p = 0.001). In addition, the wound healing was better and hospital-stay
      days were reduced in the study group (22.73 +/- 9.13 days) vs. (39.73 +/- 18.27
      days; p = 0.003). CONCLUSIONS: These results indicate that enteral glutamine
      supplementation in adult burn patients could abate the degree of infectious
      morbidity and reduce hospital-stay.

PMID- 23133154
TI  - Preoperative prediction of difficult lap chole: a scoring method.
AB  - BACKGROUND: Laparoscopic cholecystectomy (LC) has become the procedure of choice
      for management of symptomatic gallstone disease. At times it is easy and can be
      done quickly. Occasionally it is difficult and takes longer time. But there is no
      scoring system available to predict the degree of difficulty of LC
      preoperatively. AIM: To develop a scoring method to predict difficult LC
      preoperatively. MATERIALS AND METHODS: There were 228 cases in 2 years, operated
      by a single experienced surgeon. There are total 15 score from history, clinical,
      sonological findings. Score up to 5 predicted easy, 6-10 difficult and >10 are
      very difficult. RESULTS: Prediction came true in 88.8% for easy and 92% difficult
      cases there were no cases with score above 10. The factors like BMI > 27.5 (p <
      0.010), previous hospitalization (p < 0.001), palpable GB (p < 0.01) US-Thick
      walled GB (p < 0.038) are found of statistical significance in predicting
      difficult LC. CONCLUSION: The proposed scoring system is reliable with a
      sensitivity and specificity of 75.00% and 90.24%, respectively.

PMID- 23133155
TI  - Diagnostic sensitivity of enzyme-linked immunosorbent assay for IgG in hydatid
      disease.
AB  - CONTEXT: Hydatid disease in humans is most commonly caused by Echinococcus
      granulosus and results in development of cysts in various organs of body. The
      diagnosis is made by serology i.e. by estimation of antibody levels or on imaging
      studies. Enzyme-linked immunosorbent assay (ELISA) is widely used for serological
      confirmation of the disease. AIM: To study the sensitivity of ELISA for IgG
      antibodies against E. granulosus in detecting hydatid disease of liver or lung.
      SETTINGS: A retrospective study of serology of all surgically confirmed cases of
      hydatid cysts of liver or lung in a tertiary level hospital. METHODS AND
      MATERIAL: The levels of IgG antibodies against Echinococcus, measured by ELISA,
      in patients of cystic lesions of liver or lung, who underwent surgery for the
      same and confirmed as having hydatid disease, during surgery or on
      histopathological examination after surgery, were recorded and analysed. There
      were 28 such patients from January 2001 to 2007. Twenty-three patients with
      hydatid cysts in liver and 4 in lung were included. One patient with hydatid
      liver was excluded from the study due to heavily calcified cyst. RESULTS: Two
      types of kits were used; one using crude antigen and other using purified
      antigens. Among 23 patients with hydatid cysts of liver, 8 had positive serology
      while 15 had either equivocal or negative results. All 4 patients with hydatid of
      lung had positive serology. CONCLUSION: ELISA test is not sensitive enough to be
      relied upon for confirmation of hydatid disease and considering its high cost, an
      alternative more specific, sensitive, cheaper and easily available test needs to
      be evaluated for confirming hydatid disease.

PMID- 23133156
TI  - Systemic inflammatory response syndrome outcome in surgical patients.
AB  - INTRODUCTION: The problems of inflammation and infection as a leading cause of
      organ dysfunction and failure is a major problem after injury or operations. When
      systemic inflammatory response syndrome (SIRS) progress to multiple organ failure
      (MOF), the mortality reach up to 30-80% depending on the number of failed organs.
      Recent discoveries and improvement in patient care, a reasonable question then
      arises, are the incidence of MOF decreasing? The literature suggests a decrease
      in mortality of patients with severe organ failure and a decrease in elective
      surgical mortality in patients. METHODS: This is prospective study of 50 patients
      who underwent surgical procedure. They were followed up till date of termination
      with daily SIRS monitoring, development of MODS and MOF. Risk factors for MOF are
      addressed. RESULTS: There are total 31 patients who develop SIRS, of whom 7
      patients develop severe sepsis and 4 went into MOF. CONCLUSION: Early detection
      of SIRS helps us to prevent multiple organ dysfunction syndrome (MODS)/MOF,
      leading to lesser hospital stay and better outcome.

PMID- 23133157
TI  - Adult filarial worm in the tissue section of a breast lump.
AB  - Filariasis is a global health hazard. Incidence of filariasis is remarkably high
      in Indian sub continent. Apart from typical cases it is not common to find
      microfilaria and adult worm in tissue section and needle aspiration of the breast
      lump. Presence of microfilaria and adult worm in the breast is a rare finding. We
      report a case of filarial nodule in the breast of a 40 years old woman who
      presented with a pain less mass in the breast since last one month. It was
      diagnosed as fibroadenoma breast. Fine needle aspiration cytology showed mainly
      chronic inflammatory cells. The nodule was excised in toto and processed for
      histopathological examination. Histopathology confirmed the adult worm with
      granuloma in the breast nodule.

PMID- 23133158
TI  - Tubercular splenic abscess in immunocompetent patients: a rare entity.
AB  - Splenic abscess is an unusual, potentially life threatening condition associated
      with septiceamic conditions. Splenic abscess due to tuberculosis is a rare
      entity, specifically seen in immunocompromised individuals. However splenic
      tubercular abscess in immunocompetent individuals is rarer. We present two cases
      of splenic tubercular abscess in immunocompetent persons where a diagnosis of
      tuberculosis was made after splenectomy. The aim of presenting these cases is to
      stress the fact that tuberculosis should be considered as a differential
      diagnosis in all cases of splenic abscesses in areas where tuberculosis is
      endemic.

PMID- 23133159
TI  - Pigmented basal cell carcinoma.

PMID- 23133160
TI  - Partial fistulotomy and multiple setons in high anal fistulae.
AB  - Setons are employed in high perianal fistulae. Our study aimed to use multiple
      setons in addition to a partial fistulotomy in high perianal fistulae involving
      the sphincter complex to combine the effects of cutting and drainage of the
      fistulous tract. This prospective study included 16 patients over a period of 4
      years who presented with high perianal fistulae. The internal opening was
      identified and tract laid open till the dentate line. Four prolene threads were
      passed along the remainder of the tract and taken out through the external
      opening. One was tied tightly while the others were tightened every 7 days. No
      patients developed major faecal incontinence. Fistula recurred in one patient
      within a year and one patient had occasional incontinence to flatus. Multiple
      setons after partial fistulotomy is an effective treatment for high anal fistulae
      with low incidence of incontinence and recurrence and adequate patient
      satisfaction.

PMID- 23133161
TI  - Hymenoplasty - how to do.

PMID- 23133162
TI  - Surgery of the hymen: from myth to modernisation.

PMID- 23133163
TI  - Some more about diabetic foot.

PMID- 23133164
TI  - Recognition - IJS indexed in SCI expanded!

PMID- 23133165
TI  - Common bile duct stones - their presentation, diagnosis and management.
AB  - Common Bile duct stones (CBD) continue to pose a significant problem both to the
      patient and the Surgeon. They increase the morbidity of a patient undergoing
      Cholecystectomy from less than 5% to as much as 20% and almost zero mortality to
      as high as 30%. Recent times have thrown up a fair share of controversy in the
      management of this condition both due to technological innovations and
      costreduction-pressures. The aim in CBD stone disease, as in any benign disease
      is to discover a therapeutic algorithm with minimal morbidity, no mortality and
      at reasonable cost. This can be achieved only by a thorough understanding of the
      disease and also the available diagnostic and treatment modalities.This article
      dicusses the diagnosis, investigation and therapy of Common Bile Duct Stones
      (CBD) and gives a therapeutic algorithm.

PMID- 23133166
TI  - Jejunal diverticulae: reports of two cases with review of literature.
AB  - INTRODUCTION: Jejunal diverticulosis (JD) is a rare disease of elderly people.
      Majority of diagnosed individuals are asymptomatic and found incidentally. The
      disease is clinically significant because of associated potential risk of serious
      complications. Due to the rarity and variable presentation of this clinical
      entity, diagnosis is often difficult and delayed, resulting in unnecessary
      morbidity and mortality. Clinical presentations, signs, diagnosis, complications
      and treatment of JD are discussed through a review of the literature and report
      of two cases. METHODS: A literature review was done for analysis of diagnosis,
      treatment and complications of JD. Two cases of JD diagnosed and treated in our
      institution are also presented. CONCLUSION: JD is a rare disease which has
      variable presentations and thus poses a challenge to our diagnostic skills.
      Awareness about complications and presentation of the condition is needed for
      early detection and avoiding unnecessary mortality.

PMID- 23133168
TI  - Integrated clinical care pathway for managing necrotising soft tissue infections.
AB  - BACKGROUND: Necrotising soft tissue infections (NSTI) are relatively common
      infections with high morbidity and mortality rate, as they often present late in
      their course. Quick and aggressive surgical treatment improves survival and
      decreases hospital stay. MATERIALS AND METHODS: All patients with NSTI managed at
      our centre from June 2007 to January 2009 were included in this prospective
      study. We evaluated various parameters like age, co-morbidities, biochemical
      parameters, time interval between admission and first operative intervention,
      against duration of hospital stay and out come of the case. RESULTS: Fifty-four
      patients with NSTI were admitted and treated during the study period. Male to
      female ratio was 6:1. Mean time interval between admission and operative
      intervention was 6 hours. Mean period of hospitalisation was 53 days and we had
      limb salvage rate of 100% and one mortality (1.85%). Diabetes mellitus was the
      most common co-morbid condition and Staphylococcus aureus the most common
      isolate. Presence of leucocytosis, hyponatraemia, hypoalbuminaemia, anaemia and
      deranged renal functions were found to be poor prognostic factors. CONCLUSION:
      Late and varied presentation is the rule rather than exception with NSTI. Early
      recognition of the condition, with emergency operative intervention and repeated
      debridement by a dedicated surgical team, is the key to patient survival and limb
      salvage.

PMID- 23133167
TI  - Challenges in the diagnosis of blunt cardiac injuries.
AB  - INTRODUCTION: Blunt thoracic injuries (BTIs) are directly responsible for 20-25%
      of all deaths, worldwide. Involvement of heart in BTIs is largely underestimated
      and ignored, but reasonable estimate would be around 15%. This study was planned
      to emphasize on clinical-presentation and diagnosis of blunt cardiac injuries
      (BCIs). RESULTS: Clinical presentation of BCIs, varied from mild chest discomfort
      to haemodynamic shock secondary to rapid exsanguinations. Non-specific
      presentation with associated injuries diverts physician's attention and delayed
      appearance of clinical features makes diagnosis further difficult. Cardiac
      markers and ECG are not specific, but high sensitivity of 100% could be reached
      using combination of elevated cardiactroponin levels and alterations in ECG.
      Transoesophageal or transthoracic echocardiography, angiography, intravascular
      ultrasound and nuclear scan have proven to detect cardiac injuries in BTIs, but
      lack specificity. CONCLUSION: Patients with suspicious-ECG finding need cardiac
      monitoring for at least 24 hours. Haemodynamically stable young (<55 years)
      subjects, without underlying cardiac diseases and with normal-ECG and cardiac
      marker, could be discharged safely.

PMID- 23133169
TI  - Laparoscopic cholecystectomy in patients with empyematous cholecystitis: an
      outcome analysis.
AB  - BACKGROUND: Laparoscopic cholecystectomy (LC), the procedure of choice for
      elective cholelithiasis, is now also used in the management of acute
      cholecystitis. Empyema of the gallbladder is unexpectedly encountered in a
      proportion of these patients. This paper describes our experience with LC in the
      treatment of patients with empyema of the gallbladder. METHODS: From May 1992 to
      July 2007, 315 patients with a clinical diagnosis of acute cholecystitis
      underwent LC. Operative and histopathology reports were used to identify patients
      with empyema of the gallbladder, to which retrospective chart reviews were
      applied. Factors associated with conversion and complications were assessed to
      determine their predictive power. RESULTS: Being male and having high levels of
      aspartate transaminase (AST), alanine transaminase (ALT), and white blood cells
      significantly influenced the prediction of empyema. The conversion rate was
      significantly higher for empyema and acute cholecystitis, but the complication
      rate did not differ significantly between these conditions. Previous abdominal
      surgery was an independent risk factor for conversion and complications. Also,
      temperature >37.5 degrees C, AST >60 IU/l, and ALT >60 IU/l were associated with
      higher conversion rates. The hospital stay was longer in patients with empyema,
      while the operation time did not differ between the two groups. CONCLUSION:
      Empyema of the gallbladder can be encountered in patients with presumed acute
      cholecystitis. Preoperatively differentiating between simple acute cholecystitis
      and empyema is difficult, if not impossible. The conversion rate is expected to
      be higher when empyema is approached laparoscopically than for simple acute
      cholecystitis or symptomatic cholelithiasis.

PMID- 23133170
TI  - Is hyperbilirubinaemia in appendicitis a better predictor of perforation than C
      reactive protein? - a prospective study.
AB  - PURPOSE: To compare the performance for the prediction of perforated appendicitis
      of total bilirubin versus C-reactive protein (CRP), white blood cell count, the
      time period of symptoms' evolution, and systemic inflammatory response syndrome
      (SIRS). METHODS: Prospective observational study, applying receiver operating
      characteristics curve analysis to compare the sensitivity and specificity of the
      tested variables. RESULTS: The period of symptom's evolution was prolonged (105.2
      +/- 79.3 hours vs. 38.6 +/- 17.5 hours), and CRP levels were higher in perforated
      appendicitis (176 +/- 82.6 mg/l vs. 80 +/- 76 mg/l). Most patients with
      perforated appendicitis had a SIRS score higher than 3 points. CRP (>76.7 mg/l),
      the time period of symptoms' evolution (>34.5 hours), and SIRS (3 points or
      more), were the best cutoff values to predict perforated appendicitis.
      CONCLUSIONS: Perforated appendicitis may be suspected based on CRP, SIRS and the
      time period of symptoms' evolution. We do not recommend the use of total
      bilirubin to predict perforation in appendicitis.

PMID- 23133171
TI  - Open port placement through the umbilical cicatrix.
AB  - Peritoneal access and creation of pneumoperitoneum are the key initial steps of
      laparoscopic surgery. This is commonly achieved by either introducing Veress
      needle or by gradual dissection of all the layers of the abdominal wall and then
      introducing a port under direct vision. The two techniques are extremely safe,
      but large outcome studies have found slightly increased complications with the
      Veress needle. Randomized trials do not support such finding and both techniques
      continue to have their enthusiasts. We hereby describe an open method of initial
      port placement, wherein the port is introduced through the umbilical cicatrix
      under direct vision.

PMID- 23133172
TI  - Perforated caecal diverticulum as a content of inguinal hernia - report of a rare
      case.
AB  - A tablet induced perforation of a caecal diverticulum into a hernial sac is a
      rare happening. The report discusses the presentation and outcome of a patient
      with such an unusual disease. A 55-year-old man presented with features of
      irreducible right sided indirect inguinal hernia. A hard swelling near upper pole
      of right testis was noted. Scrotal ultrasound revealed a normal testis. At
      operation caecum and proximal ascending colon were found in the hernial sac with
      the caecum adherent to the testis. As caecal malignancy could not be ruled out
      and enbloc Rt Haemicolectomy with Rt orchidectomy was performed. The patient had
      an uneventful recovery. Pathological examination of the specimen revealed a
      perforated caecal diverticulum with presence of multiple tablets in its lumen
      invaginating the upper pole of right testis without any evidence of malignancy.
      Tablet induced perforation of a caecal diverticulum into a hernial sac is a rare
      clinical entity. If malignancy cannot be negated at operation, a right
      haemicolectomy is a safe and feasible option.

PMID- 23133173
TI  - Migration of intrauterine copper 7 leading to vesical calculus.
AB  - Intrauterine contraceptive devices have been associated with multitude of
      complications including uterine perforation and migration into adjacent organs.
      Here we present a rare case report on 45-year-old lady in whom intrauterine
      copper 7 (Cu-7) migrated into the urinary bladder leading to calculus formation.
      The migrated Cu-7 alongwith the calculus were successfully retrieved.

PMID- 23133174
TI  - A rare case of 'Spontaneous rupture of partially thrombosed pseudoaneurysm of
      gastroduodenal artery associated with chronic pancreatitis'.

PMID- 23133175
TI  - CMC Vellore - in the service of our nation for more than a century.

PMID- 23133176
TI  - What's on offer for the surgical trainees at our conferences?

PMID- 23133177
TI  - Surgical oncology - at the crossroads.

PMID- 23133178
TI  - Oncology: Future trends.

PMID- 23133179
TI  - The need of the hour - a trained surgical oncologist.

PMID- 23133180
TI  - Management of differentiated thyroid cancer.

PMID- 23133181
TI  - Controversies and challenges in the management of well-differentiated thyroid
      cancer.
AB  - The incidence of well-differentiated thyroid cancer has seen a worldwide increase
      in the last three decades, although whether this is due to a 'true increase' in
      incidence or simply increased detection of otherwise subclinical disease remains
      undetermined. Nonetheless, this rising incidence has fuelled an interest in early
      diagnosis, treatment and follow-up of thyroid cancer along with greater public
      awareness. The treatment of thyroid cancer revolves around appropriate surgical
      intervention, minimising complications and the use of adjuvant therapy in select
      circumstances. Prognostic features and risk stratification are crucial in
      determining the appropriate treatment. There continues to be considerable debate
      in several aspects of management in these patients, and there is limited
      prospective data to direct therapy, hence limiting decision-making to
      retrospective analyses, treatment guidelines based on expert opinion and personal
      philosophies. The major controversies are related to diagnostic work-up, extent
      of surgery and postoperative management including the role of radioactive iodine.
      There are also differences in opinion regarding management of nodal metastases
      and follow-up protocols. As overall survival in well-differentiated thyroid
      cancer exceeds 95%, it is important to reduce over-treating the large majority of
      patients, and focus limited resources on high-risk patients who require
      aggressive treatment and closer attention. There needs to be a concerted effort
      on the part of a multidisciplinary team to recognise the nuances in treating well
      differentiated thyroid cancer.

PMID- 23133182
TI  - Thoracic cancers - cautious optimism replaces abject nihilism.

PMID- 23133183
TI  - Diagnosis, staging and treatment of patients with non-small cell lung cancer for
      the surgeon.
AB  - This article covers the risk factors, diagnostic tools, staging
      methods/modalities and treatment for patients with non-small cell lung cancer
      (NSCLC). Also presented is the new 7th edition American Joint Cancer Committee
      (AJCC) TNM classification for staging of NSCLC and a recommended treatment
      algorithm.

PMID- 23133184
TI  - Management of oesophageal cancer.
AB  - Oesophageal cancer is a disease of dismal prognosis. There are variations of
      epidemiology among different ethnic groups and geographic regions. India is a
      country with high incidence. This can be attributed to the interplay between
      environmental, dietary factors and life-style of the population of the country.
      Optimal therapeutic strategy for patients with oesophageal cancer demands
      individual consideration.Majority of oesophageal cancer patients present at an
      advanced stage of disease. Screening programmes or strategies aiming at early
      diagnosis can improve the prognosis; unfortunately this is not cost-effective
      except in very high incidence areas. Accurate staging can help select the most
      appropriate treatments, such as excluding those patients with metastatic disease
      who are unlikely to benefit from surgery, and treating very early lesions with
      endoscopic means. When surgery is indicated, treating patient in a high-volume
      centre can improve the outcome and minimise complications. Although surgical
      resection remains the main treatment modality, long-term prognosis after surgical
      resection alone has been suboptimal except in those with early disease.
      Multidisciplinary approaches including chemotherapy and radiotherapy with or
      without surgery are increasingly employed for patients with advanced disease.
      Collaboration among surgeons, clinical oncologists, radiologists and physicians
      is of utmost importance to achieve the best results. Treatment for patients
      should be individualised to enhance outcome.

PMID- 23133185
TI  - Sentinel lymph node biopsy for breast cancer - Indian perspective.

PMID- 23133186
TI  - Management of the axilla in patients with breast cancer.
AB  - This article reviews the changes in management of the axilla in patients with
      breast cancer in the last decade. It discusses the recent advances, existing
      controversies and provides evidence-based guidelines for use in clinical
      practice.Sentinel lymph node (SLN) biopsy has replaced the more morbid axillary
      lymph node dissection (ALND) and four node sampling for axillary nodal staging.
      Blue dye guided four node sampling is an acceptable alternative when radioisotope
      facilities are not available. ALND is reserved for patients with proven axillary
      lymph node involvement.Preoperative axillary ultrasound and fine-needle
      aspiration cytology or core biopsy of suspicious lymph nodes reliably identifies
      around 30% of node positive patients. Intraoperative assessment of the SLN using
      frozen section or real time molecular assays enables surgeons to perform one
      stage ALND in node positive patients. For those patients in whom intra-operative
      SLN assessment is negative, but whose final pathology reveals SLN metastasis,
      standard treatment has been to perform a completion ALND. Predictive models can
      be used to identify a lowrisk group of SLN-positive patients in whom routine ALND
      may not be necessary. In the future, completion ALND for microscopic disease will
      not be the standard of care but axillary radiotherapy may be an alternative with
      equal control and less morbidity.

PMID- 23133187
TI  - Comments on advances and future directions in management of prostate cancer.

PMID- 23133188
TI  - Advances and future directions in management of prostate cancer.
AB  - Despite the high cure rates of patients diagnosed and treated with prostate
      cancer, there is still room for improvement in management of these patients. This
      includes the identification of patients at highest risk for progression, the
      usage of focal therapies in low risk disease, and the continued improvement on
      established modalities. Through these avenues, the morbidity associated with
      treatment for prostate cancer can be vastly reduced, and thus patient outcomes
      improved. This article reviews the current treatment modalities and future
      directions for the treatment of localised prostate cancer.

PMID- 23133189
TI  - Advances in the management of gastric cancer.
AB  - Gastric cancer is a common malignancy in our country and patients continue to
      present at an advanced stage. Following confirmation of diagnosis, CT scan,
      endoscopic ultrasound and laparoscopy are the essential staging modalities.
      Radical gastrectomy remains the initial treatment of choice. Although controversy
      persists about the extent of lymph node dissection, there is a general consensus
      in performing D2 dissection but with preservation of pancreas and spleen.
      Patients who have high risk of relapse are treated with postoperative
      chemoradiotherapy. The regimen of preoperative chemotherapy followed by
      gastrectomy and postoperative chemotherapy has also become important in recent
      years. Both these chemotherapeutic options confer survival advantage and patients
      need to be appraised about various treatment strategies at the very outset.

PMID- 23133190
TI  - Surgical management of colorectal cancer: A review of the literature.
AB  - BACKGROUND: Colon cancer management continues to evolve with significant advances
      in chemotherapy, surgical technique and palliative interventions. As the options
      of therapy have improved, so have the challenges of management of primary colon
      cancer. REVIEW: A review of historical and up to date literature was undertaken
      utilising Medline/PubMed to examine relevant topics of interest-related to the
      surgical management. Enhanced knowledge of genetics associated with colon cancer
      has improved our care of patients with hereditary colon cancer syndromes.
      Additionally, traditional approaches to surgical intervention for primary colon
      cancer have been questioned and will be discussed in this review including the
      role of laparoscopy, use of mechanical bowel preparation, management of the
      primary tumour in the face of metastatic disease, as well as the role of
      palliative intervention in select patients. CONCLUSION: Colon cancer has seen
      improvement and expansion of therapeutic approaches to primary colon cancer.
      Laparoscopy and palliative interventions have become widely accepted with level I
      evidence to demonstrate good patient outcomes. Traditional dogma with mechanical
      bowel preparation has been challenged and debunked with regards to the
      efficacious benefits previously accepted. The management of the primary tumour
      has now become increasingly complex as it appears to be a reasonable approach to
      manage the primary tumour non-operatively in select cases of extracolonic disease
      requiring management.

PMID- 23133192
TI  - Surgical management of gallbladder cancer.
AB  - Gallbladder cancer is a very common malignancy in the northern part of India.
      Surgery is the only potentially curative modality of treatment for this disease.
      Radical cholecystectomy is the optimal surgical standard for resectable
      gallbladder cancer. This includes cholecystectomy, liver resection (wedge,
      segments 4b and 5, or extended right hepatectomy), and regional lymphadenectomy
      along the hepatoduodenal ligament, behind the duodenum and pancreatic head,
      common hepatic artery and celiac axis. Controversies regarding extent of liver
      resection, lymphadenectomy and role of multiorgan resection have been discussed.
      Incidental gallbladder cancer is often detected on histopathologic examination of
      the simple cholecystectomy specimen removed for a presumed gallstone disease.
      Revision surgery should be performed for incidental cancers that invade
      muscularis propria or beyond (T1b or more). Advanced gallbladder cancer should be
      treated non-operatively with a palliative intent. Obstructive jaundice in the
      setting of an advanced gallbladder cancer can be palliated with biliary stenting
      by endoscopic or transhepatic means. Occasionally, a surgical biliary bypass may
      be indicated to relieve intractable pruritus in a jaundiced patient with
      gallbladder cancer. There is no role of a planned R2 resection of advanced
      gallbladder cancer for the purpose of cytoreduction. Further improvement in the
      management of gallbladder cancer will need integration of systemic chemotherapy
      with radical surgery.

PMID- 23133191
TI  - Current evidence-based opinions in the management of adenocarcionoma of the
      rectum.
AB  - The management of rectal cancer has drastically evolved over the past two decades
      as a result of implementation of circular stapling devices and the introduction
      of neoadjuvant chemoradiation. In spite of current aggressive multimodality
      treatments, the recurrence rate remains unacceptably high and the expected 5-year
      survival in patients who develop recurrent disease is dismal. The management of
      rectal cancer must involve a multidisciplinary approach. An understanding of the
      biology of rectal tumours may allow for selection of patients who may have an
      aggressive phenotype allowing for alterations in the operative and neoadjuvant
      planning. Efforts to improve local control and survival in rectal cancer are the
      focus of multiple current clinical and preclinical research efforts. Preoperative
      chemoradiation for and surgical management of rectal cancer, including the
      laparoscopic approach are areas of dynamic progression. In the present report, we
      review the current evidence in the new strategies pertaining to the multimodality
      approach in the management of rectal cancer.

PMID- 23133193
TI  - Management of pancreatic cancer: Current status and future directions.
AB  - Despite advances in surgery and adjuvant therapy pancreatic ductal adenocarcinoma
      has a dismal prognosis. Surgical resection with negative margins remains the
      mainstay of treatment, and results can be improved with neoadjuvant therapy when
      the lesion is of borderline resectability. Extended lymphadenectomy has no role
      in improving survival, but may worsen quality of life. Venous resection can be
      performed if it helps to achieve an R0 resection, but arterial resection is not
      justified. A host of newer agents, both cytotoxic and targeted, are being
      evaluated. The article summarizes the critical issues and looks ahead to the
      future.

PMID- 23133194
TI  - Cancer in pregnancy.

PMID- 23133195
TI  - Cancer in pregnancy.
AB  - Cancer during pregnancy is a rare situation which demands a multidisciplinary
      care involving the surgical oncologist, the medical oncologist, the obstetrician
      and a host of other care givers. The care of the patient is planned in a way to
      optimize the health care delivery to the mother without compromising on the care
      of the fetus. When this is not possible priorities need to be established and
      harsh decisions taken on an individual basis. The treatment of the cancer does
      not change from the standard outside the limits described above and the objective
      should be to stay as close to the standard of care treatment as possible.

PMID- 23133196
TI  - Message from the President of ASI-2010.

PMID- 23133197
TI  - Surgery of parathyroid.
AB  - Surgery of parathyroid revolves around the management of hyperparathyroidism
      (HPT). In most cases, occurrence is sporadic rather than familial, and 80-85% of
      cases of sporadic primary HPT are caused by a solitary parathyroid adenoma. The
      diagnosis is made by hypercalcaemia with an inappropriately elevated parathyroid
      hormone (PTH) level and a 24-hour urine calcium excretion level that is normal or
      high. Improved assay for PTH has led to earlier detection of HPT and has been
      responsible for the apparent increase in the prevalence of the disorder. An
      improvement in preoperative localisation studies as well as the development of a
      rapid intraoperative PTH assay has changed the approach to parathyroid surgery in
      the last two decades. This article provides a brief overview of management of
      primary HPT.

PMID- 23133198
TI  - Persistent mullerian duct syndrome: How to deal with the mullerian duct remnants 
      a review.
AB  - Persistent mullerian duct syndrome (PMDS) is usually a surprise finding either
      during orchidopexy or during routine inguinal hernia repair in male patients.
      Often, the surgeon would face a dilemma about what is to be done with the
      remnants of mullerian duct, i.e. the fallopian tubes, uterus and proximal vagina.
      Till recently, it was advised to retain these structures whenever it was felt
      that the complete excision of these structures may jeopardise the blood supply
      and integrity of the vas deferens. Recent reports of malignancy in these retained
      structures would justify more aggressive approach. In our patients with PMDS, we
      have removed the mucosa of the retained mullerian structures, without
      compromising the integrity and vascularity of the vas deferens, thus reducing the
      chances of malignancy.

PMID- 23133199
TI  - Review of surgical ventricular restoration: A procedure to treat cardiac failure.
AB  - Severe heart failure refractory to medical treatment necessitates the use of
      other modalities of treatment. Surgical ventricular restoration (SVR) surgery can
      provide relief until donour hearts are available or when transplantation is
      contraindicated. In this review we look at the physiological basis for
      improvement in cardiac function and cardiac and haemodynamic changes that occur
      after SVR. We also compile the reported factors affecting surgical outcome,
      criteria for patient selection and predictors of postoperative mortality. NYHA
      class, presence of diastolic failure, severe impairment of contractile function
      and presence of mitral regurgitation were the most important determinants.
      Various different procedures for achieving SVR are briefly discussed. Importance
      of mitral valve repair/replacement, coronary artery bypass grafting and
      intraoperative echocardiography in improving postoperative result is highlighted.
      Role of perioperative medication (anti-arrhythmics, ACE inhibitors and beta
      blockers) is briefly studied at the end of the review.

PMID- 23133200
TI  - Efficacy of topical recombinant human platelet derived growth factor on wound
      healing in patients with chronic diabetic lower limb ulcers.
AB  - BACKGROUND: Lower extremity ulcers are a serious complication of diabetes
      mellitus (DM). These ulcers show decreased angiogenic response and production of
      growth factors. Recombinant human platelet derived growth factor (rhPDGF) has
      been found to decrease the time to healing. This study was conducted to evaluate
      its efficacy in the treatment of diabetic foot ulcers. METHODS: A total of 50
      patients with type 1 or type 2 DM and chronic ulcers, of at least 4 weeks
      duration, were studied. They were randomised into two groups, of 25 patients
      each. The patients in group 'A' (test group) received treatment with topical
      application of rhPDGF gel and those in group 'B' (control group) were treated
      with local application of KY Jelly as a placebo. A standardised regimen of good
      wound care was provided to both groups. Healing or reduction in size of the
      wound, over a period of 10 weeks after commencement of treatment was recorded.
      RESULTS: The mean age of the patients was 49.9 years in the control group and
      56.2 years in test group. The median duration of ulcer at time of enrolment in
      the study was 6 weeks in control and 5 weeks in test group. Fifteen ulcers in
      control group belonged to IAET (International Association of Enterostomal
      Therapy) class III and 10 ulcers to class IV where as 16 ulcers were in IAET
      class III and 9 ulcers in IAET class IV in the test group. The mean size of the
      wounds was 26.5 +/- 2.5 cm(2) in control group and 29.9 +/- 3.4 cm2 in test
      group. All patients tolerated the test medication well. At the end of 10 weeks,
      18 (72%) ulcers had healed in control group and 15 (60%) in test group (p >
      0.05). Three ulcers in control group showed >75% reduction in size compared to 2
      in the test group (p > 0.05). CONCLUSION: This study did not show any
      statistically significant improvement in ulcer healing rates after the use of
      topically applied rhPDGF.

PMID- 23133201
TI  - A newly designed SIPC device for management of lymphoedema.
AB  - PURPOSE: Using (Sequential) intermittent pneumatic compression (SIPC) is one of
      the most appropriate nonsurgical treatments for lymphoedema. In this study, we
      introduce a new mode for SIPC and evaluate its clinical results with higher
      pressures. METHODS: Participants included 43 lower limb lymphoedema patients who
      underwent high pressure SIPC. Limb circumference pre- and post-SIPC were
      evaluated. RESULTS: The mean reduction of the affected limb oedema was
      approximately 75%, which is regarded as a good response to the short-term
      treatment. Patients with disease duration more than 20 years didn't show a good
      or excellent response. Also the foot area had the least degree of reduction of
      oedema. CONCLUSION: We concluded that, the suggested mode may provide more
      acceptable results compared with the other This mode allows unidirectional
      forward lymph flow and associated high pressure usage well tolerated in chronic
      cases of the disease.

PMID- 23133202
TI  - Amoebic liver abscess: presentation and complications.
AB  - BACKGROUND: Amoebic liver abscess (ALA) is the most common inflammatory space
      occupying lesion of the liver. It has a highly variable presentation causing
      diagnostic difficulties. Untreated, complicated ALA has high morbidity and
      mortality. OBJECTIVE: To study the various types of clinical presentation and
      complications of ALA in order to establish early diagnosis and prevent
      complications. MATERIALS AND METHODS: A prospective study was conducted in the
      Department of Surgery of Calcutta National Medical College and Hospital from July
      2005 to June 2008. All patients with a confirmed diagnosis of ALA during this
      period were included in the study. RESULTS: Seventy-two patients with 76 ALAs
      were studied over a 3-year period. The age ranged from 21 to 72 years (mean age
      being 43.64 years). There were 66 males (91.67% of the patients) and 6 females
      (8.33% of the patients). The (31-40 years) age group showed the highest incidence
      consisting of 40.28% of the cases. Pain was located most commonly in the right
      hypochondrium in 60 patients (83.33%). Fever was observed in 58 patients
      (80.56%). Solitary abscess cavity was present in 68 patients (94.44%). The right
      lobe alone accounted for 65 (85.53%) of the abscesses. The most common echo
      pattern encountered in ultrasonography was the echorich pattern in 54 (71.05%)
      abscesses. Forty-four patients (61.11%) gave history of alcohol consumption.
      Diagnosis was missed in 21 patients (29.17%), particularly in those with atypical
      presentations. The most common complication was pleuropulmonary in 24 patients
      (33.33%), followed by intraperitoneal rupture in 19 patients (26.39%). Other
      complications were jaundice (n = 11), ascites (n = 9), subhepatic effusion (n =
      7), subphrenic abscess (n = 3) and intrapleural rupture (n = 2). Ultrasonography
      was useful in diagnosing ALA. Despite successful therapy 23 patients (31.94%) had
      residual abscess cavities on ultrasonography even after 6 months. CONCLUSION: In
      an endemic area a patient presenting with lower chest or upper abdominal pain
      along with tender hepatomegaly should raise the suspicion of ALA. Sonography
      remains an important tool in the diagnosis of ALA.

PMID- 23133203
TI  - Combined use of modified Alvarado score and USG in decreasing negative
      appendicectomy rate.
AB  - INTRODUCTION: Appendicitis is notorious in its ability to simulate other
      conditions and in the frequency it can be mimicked by other pathologies. Despite
      extraordinary advances in modern radiography imaging and diagnostic laboratory
      investigations the accurate diagnosis of acute appendicitis remains an enigmatic
      challenge. Of the various commonly used diagnostic aids for appendicitis, no
      single test can reduce the rate of negative appendicectomy to zero. MATERIALS AND
      METHODS: Fifty admitted cases of suspected appendicitis were subjected to
      ultrasonography (USG). All the patients were scored out of 9 according to
      modified Alvarado score. A treatment plan was devised according to which patients
      with modified Alvarado score >=7 underwent immediate appendicectomy even if USG
      was negative for appendicitis and patients with score <7 underwent appendicectomy
      if USG was positive for appendicitis. RESULT: 84.3% of males and 44.4% of females
      admitted as case of suspected appendicitis had confirmed appendicitis. Due to
      high sensitivity (97.14%) and accuracy (92%) of our diagnostic approach, 85.71%
      cases of appendicitis were diagnosed in early stage, with only 8.57% perforation
      and abscess rate, leading to post appendicectomy complication rate of only 5.14%
      in our study (one wound infection and one urinary retention). We could achieve
      low negative appendicectomy rate of 7.14% in males and 11.11% in females and
      overall 8.11% in our study. CONCLUSION: Combined use of modified Alvarado score
      and high frequency USG not only reduces negative appendicectomy rate but also
      reduces morbidity and postoperative complications.

PMID- 23133204
TI  - Fungal colonisation in burn wounds: An Indian scenerio.
AB  - Burn patients are susceptible hosts for fungal colonisation. AIM: To study
      incidence and profile of fungal colonisation of burn wounds. MATERIALS AND
      METHODS: This prospective study was conducted in 201 consecutive adult patients
      (39 male and 162 female) with burn wounds, admitted from October 2005 to
      September 2006. Wounds with clinical suspicion of fungal colonisation were
      biopsied and examined by wet smear, Potassium hydroxide (KOH) mount, nigrosin
      stain, 1% Acid fast bacilli (AFB) stain, Gomori methenamine silver (GMS) stain,
      histopathological examination and fungal culture. All wounds with suspicion of
      fungal colonisation were treated with topical application of miconazole ointment
      mixed with povidone-iodine/silver sulphadiazine topically and itraconazole (oral)
      systemically. RESULTS: Fungal infection of burn wound was suspected in 77
      patients (38.31%) with 20-70% total body surface area (TBSA) burns. Ninety-two
      biopsy samples were collected from 77 patients. On investigations, fungal
      colonisation was confirmed in 35 patients. Culture was positive in 23 patients
      with Candida in 12 and Aspergillus in 4. GMS stain and KOH stain showed
      sensitivity and specificity of 70.8% and 86.5%, respectively for detecting fungi
      in burn wound. Nigrosin stain was negative in all patients. Duration of
      hospitalisation was more in patients having fungal colonisation without any
      significant effect on the mortality DISCUSSION: In 38.31% of patients fungal
      colonisation was clinically suspected and it was confirmed in 17.41% of 201
      patients. GMS stain and KOH stain were observed to have acceptable sensitivity
      and specificity. With increasing prevalence of Aspergillus, flucanazole cannot be
      relied upon in controlling fungal colonisation and drugs like itraconazole may
      have to be used as empirical therapy. CONCLUSION: Fungal colonisation of burn
      wound is not uncommon and should be suspected. Fungi detected most commonly were
      Candida and Aspergillus. KOH and GMS stain were identified as reliable, simple
      and inexpensive methods for confirming fungal colonisation.

PMID- 23133205
TI  - Role of proliferative markers in breast lesions.
AB  - BACKGROUND: Carcinoma of breast is a leading cause of death in women throughout
      the world. Difficulty in diagnosis occurs in routine Hematoxylin and Eosin (H&E)
      stained sections to differentiate premalignant lesions like epitheliosis and
      malignant lesions like carcinoma in situ which may affect prognosis. AIMS: Our
      study was done to assess the role of proliferative markers in this field.
      MATERIALS AND METHODS: In this study, total 66 cases of different breast lesions
      were studied by H&E stained sections as well as proliferative markers like silver
      staining nucleolar organizer region (AgNOR) and proliferating cell nuclear
      antigen (PCNA). RESULTS: Statistically significant differences found in
      expression of proliferative markers between most of them. CONCLUSION: Study of
      proliferative markers help in the proper diagnosis of different breast lesions
      which lies in the grey zone on routine histopathology.

PMID- 23133207
TI  - Management of heel ulcers in insensate foot by using free prefabricated radial
      fascial flap - a new flap.
AB  - Heel ulcers are common in insensate foot. The management of such ulcers require
      tissue not only to resurface the skin defect, which is small in most of the
      cases; but also well vascularised tissue to fill the cavity which results after
      excision of the ulcer. We have described a new flap prefabricated radial fascial
      flap, by which both aims are achieved easily.

PMID- 23133206
TI  - Type IVa choledochal cyst: Results following haemihepatectomy and mucosectomy of
      intrahepatic cyst.
AB  - Choledochal cyst is a rare condition characterised by congenital dilatation of
      the biliary tree. Commonly seen in the oriental countries, patients usually
      present with a varying combination of abdominal pain, jaundice, lump or
      cholangitis. Untreated patients or incomplete removal of the cysts usually leads
      to portal hypertension and cholangiocarcinoma. Almost one-third of the cases have
      intrahepatic cyst, making complete cyst excision often impossible. We are
      reporting a 9-year-old girl with type IVa choledochal cyst presented to us with
      recurrent pain abdomen and intermittent jaundice for 1 year. Excision of
      extrahepatic cyst, left hepatectomy, mucosectomy of the residual cyst wall of
      right lobe of the liver and a wide bilioenteric anastomosis was done. Patients
      followed up with an magnetic resonance cholangiopancreatography (MRCP) 2 months
      later showed shrinkage of the residual cyst and good bile drainage. Mucosectomy
      of intrahepatic cyst may prevent recurrent cholangitis, calculus formation and
      cholangiocarcinoma in the long run.

PMID- 23133208
TI  - Simple and effective method of heat therapy in lymphoedema.
AB  - Heat therapy is a well known conservative management for lymphoedema. We are
      describing here a heat therapy apparatus which is easy to make, cheap,
      transportable, easily reproducible and maintenance free and found to be very
      effective.

PMID- 23133209
TI  - Contralateral male breast cancer with a positive family history - a case report
      with review of literature.
AB  - Male breast cancer is an uncommon disease. The incidence of male breast cancer
      has been found to be gradually but steadily increasing. However, because of
      rarity of this disease, it is not exhaustively studied and discussed when
      compared to the female counterpart. The occurrence of a contralateral breast
      cancer in a male is much rarer. We are reporting a case of contralateral male
      breast cancer with a positive family history. This is an uncommonly reported
      entity. The relevant literature has been reviewed and a brief discussion on the
      current concepts on male breast cancer has been added.

PMID- 23133210
TI  - Duodenal perforation in a 14-year-old boy with abdominal tuberculosis despite
      being on antituberculous treatment.
AB  - We are presenting a case of a 14-year-old male patient with known history of
      abdominal tuberculosis on medication for 4 months with frank peritonitis and air
      under the diaphragm found to have primary perforation of the duodenum due to
      tuberculosis. Tuberculosis is common in the third world but affects iliocaecal
      junction commonly. Cases with tuberculous duodenal are rarely reported in the
      literature.

PMID- 23133211
TI  - Parathyroid cyst: a rare case report.
AB  - Parathyroid cysts are rare lesions arising in the neck and anterior mediastinum.
      Fewer than 250 cases have been pub lished in the literature. Parathyroid cysts
      constitute only 0.6% of all thyroid and parathyroid lesions, but should be
      considered in the differential diagnosis of anterior neck masses, particularly in
      the presence of hypercalcaemia.

PMID- 23133212
TI  - A foreign body in the rectum.

PMID- 23133213
TI  - Vanishing lung syndrome.

PMID- 23133214
TI  - Mixed mucinous carcinoma of male breast: a rare presentation.

PMID- 23133215
TI  - Haemangiomas versus vascular malformations: correct diagnosis for correct
      treatment.

PMID- 23133216
TI  - How to review an article.

PMID- 23133217
TI  - Triple assessment in the diagnosis of breast cancer in Kashmir.
AB  - BACKGROUND: Although the diagnosis of breast cancer is suggested on clinical
      examination, the degree of suspicion is variable. Currently a combination of
      three tests, i.e. clinical examination, radiological imaging (mammography,
      ultrasonography) and pathology called as triple assessment test is used to
      accurately diagnose all palpable breast lumps. Together they give sensitivity of
      99%. The triple assessment is taken as positive if any of the three components is
      positive and negative only if all of its components are negative for malignancy.
      MATERIALS AND METHODS: This study was conducted in the Department of Surgery,
      Government Medical College, Srinagar, Kashmir over a period of 3 years from June
      2005 to May 2008. A total of 200 patients with a breast lump were selected
      irrespective of age. A detailed history, focused clinical examination,
      radiological imaging and fine-needle aspiration cytology (FNAC) were used as
      diagnostic tools for screening of the patients. The aim of this study was to
      evaluate accuracy of triple assessment in the preoperative diagnosis of patients
      with breast carcinoma. RESULTS: The sensitivity and specificity of all the
      modalities used in triple assessment when combined together was 100% and 99.3%,
      respectively. The concordance for the triple assessment was 99.3%, positive
      predictive value was 93.3%, negative predictive value was 100%, sensitivity was
      100% and specificity was 99.3%. p value was significant (0.000). CONCLUSION: We
      conclude that triple assessment is a very useful diagnostic tool to evaluate
      patients with breast lumps and to detect patients with breast cancers with an
      overall accuracy of 99.3%.

PMID- 23133218
TI  - Rare cause of intestinal obstruction - Vaginal enterocele.
AB  - In surgical emergency admissions, acute abdomen with intestinal obstruction is
      very common problem. Many causes of intestinal obstruction are there but most
      common once are postoperative bands and adhesions, hernias, tumors and congenital
      bands. Here we report very rare and unusual cause of acute abdomen with
      intestinal obstruction in a non hysterectomized 78-year-old female having pelvic
      herniation i.e. anterior and posterior vaginal enterocele, in which loop of
      intestine got entrapped, strangulated and became gangrenous. Exploratory
      laparotomy was performed and resection anastomosis of small bowel was done with
      obliteration of pouch of Douglas (Rectouterine space) and utero-vesicle space.

PMID- 23133219
TI  - Quality-of-life: A study on patients of carcinoma breast and its pitfalls in
      Indian society.
AB  - BACKGROUND: Traditionally outcomes of treatment have been limited to survival.
      However, the disease and its treatment may have an impact on Quality-of- Life
      (QoL). The major concerns for patients of carcinoma breast involved are survival,
      appearance and a fear of recurrence. In Indian society we may need a separate and
      modified approach to assess QoL.  AIMS #ENTITYSTARTX00026; OBJECTIVE: The aim of
      this study was to assess the QoL of patients of carcinoma breast and to
      ascertaining pitfalls for suitable correction in future studies on Indian
      patients.  MATERIALS #ENTITYSTARTX00026; METHODS: 250 diagnosed patients of
      carcinoma breast were studied by a questionnaire on physical and psychological
      parameters. The results were assessed for applicability to our clientele.
      RESULTS: We found that majority of patients enjoy a good and non-capacitating
      QoL. Factors that may contribute to poorer health perceptions and QoL include
      experiencing a menopausal transition as part of therapy, and feeling more
      vulnerable after cancer. Overall QoL was better in the older and illiterate
      patients. Patients with no co morbidity and early stage disease fared better
      against patients with co morbidities and advanced stage of malignancy. The
      parameters used in QoL studies in west may not be directly applicable to Indian
      patients but it does give us a start. We need to adapt to these parameters and
      draw our conclusion. But there are many methodological challenges inherent in
      working with our population. Researchers interested in studying our clientele's
      QoL need to be cognizant of certain issues to ensure high quality results.

PMID- 23133220
TI  - Gastrointestinal stromal tumours: Our experience.
AB  - BACKGROUND: Gastrointestinal stromal tumours (GIST) are histologically
      heterogenous group of mesenchymal tumours arising in gastrointestinal tract
      (GIT), though they represent only 0.2% of all GI tumours. The advent of effective
      chemotherapy for GIST has altered but not diminished the role of surgery which
      remains the standard therapy for all resectable non-metastatic tumours. PURPOSE:
      To present our experience of management of GIST which are most common sarcomas of
      the GIT, commonly seen in stomach and small bowel. METHODS: All cases of GIST
      managed at our centre from April 2006 to June 2008 were included in the study.
      RESULTS: Thirteen cases of GIST were operated in the study period. Commonest
      presenting symptoms were, lump abdomen and dull abdominal pain. After initial
      USG, CECT was done in all cases. Tumour was seen to arise from small bowel
      (7/13), stomach (4/13) and one each from oesophagus and omentum. Resection and
      anastomosis was done in (12/13) cases, one case was inoperable at surgery.
      Histopathological examination confirmed GIST in all. Immunohistochemistry studies
      were done in 4/13 cases. 2/13 patients required postoperative chemotherapy.
      CONCLUSION: GIST has varied presentation as shown by our study. All patients
      require accurate delineation by CECT scan and individualised management.
      Immunohistochemistry should be done in all, and those who are in high risk group,
      metastatic or unresectable require imatinib mesylate. Patients who are CD117
      positive show good response to imatinib mesylate. Six monthly follow up is
      recommended with USG/CECT.

PMID- 23133221
TI  - Preoperative ultrasound guided needle localisation for non-palpable breast
      lesions.
AB  - BACKGROUND: Breast cancer is a major cause of cancer-related morbidity and
      mortality in Indian women. Most cases present late and thus survival in Indian
      patients is poor compared to the western world. In the absence of a screening,
      early detection of breast cancer is a challenge in Indian subcontinent. METHOD:
      Though much is known about management of any palpable lump in breast, clear
      guidelines in dealing with non-palpable lesions of breast is still obscure.
      Careful imaging of breast followed by assignment of standard Breast Imaging
      Reporting and Data Systems (BIRADS) category to the finding can go in a long way
      to predict chances of malignancy in a non-palpable breast lesion (NPBL). Total 22
      patients with impalpable lesions in the breast were localised with US guided
      needle and lesion excised. Applicability of Ultrasonography (USG) to detect early
      breast lesions and comparison with mammography in predicting malignancy was
      assessed by tests of proportions (z test). RESULTS: Total of three early breast
      cancers and four borderline lesions were diagnosed by this method among 22
      properly selected cases. Needle localisation of the lesion on sonographic
      guidance followed by lumpectomy can be both an accurate diagnostic and
      therapeutic method to deal with occult lesion in our scenario. CONCLUSION: US
      guided lumpectomy is a feasible alternative to other methods and is effective in
      Indian scenario to diagnose early subclinical breast cancers.

PMID- 23133222
TI  - Traumatic extradural hematoma - role of non-surgical management and reasons for
      conversion.
AB  - BACKGROUND: To study the role of conservative management and various reasons for
      conversion to surgical intervention in traumatic extradural hematoma (EDH).
      SETTING: Government Medical College Jammu. MATERIALS AND METHODS: One hundred
      twenty trauma patients diagnosed as extradural hematoma on CT scan were managed
      during 1 year period. OUTCOMES: Role of conservative management and various
      reasons for conversion to surgical intervention were studied. RESULTS: Out of
      these 120 patients admitted 67 were managed conservatively, 53 cases were
      operated upon. 31 were operated upon immediately and 22 were operated upon as
      delayed. There was 1 death and 4 had poor outcome in this group of patients.
      CONCLUSION: It is stressed that small size <10 ml, GCS >12 and locations other
      than temporal area are the criteria for conservative management. Twenty-two
      patients out of 89 were needed to be treated surgically during the course of
      conservative management due to neurodeterioration, increase in size of hematoma
      on CT, bradycardia, hemiparesis, pupillary abnormalities, delay in referral and
      only 18% had poor outcome. A strict vigilance is to be kept for clinical
      deterioration and various reasons mentioned above are to be kept in mind and
      patients should be subjected to repeated CT scan. Early diagnosis and immediate
      surgical intervention had good outcome, which shows the fruitful results of early
      diagnosis and intervention.

PMID- 23133223
TI  - Radiographic griding of subcutaneous soft tissue metallic foreign bodies in
      emergency department.
AB  - Radiographic grid for localization of soft tissue metallic foreign bodies is a
      modification of traditional radiography. Twenty localization procedures using
      simple radiographic grid was successfully performed. Its low cost and easy to
      perform makes it a useful tool in emergency setting.

PMID- 23133224
TI  - The economical way to off-load diabetic foot ulcers [Mandakini off-loading
      device].
AB  - We all know that increased plantar foot pressure is a leading cause of ulceration
      in the diabetic population. Healing of these ulcers requires adequate blood
      supply, control of infection, excellent wound care and 'offloading' or pressure
      redistribution of the ulcerative area [1, 2]. Out of all these factors,
      'offloading' is a unique challenge in treating chronic wounds. As diabetic foot
      care has evolved over the years, podiatrists have used numerous approaches
      including complete bed rest, cutout felt pads, crutches, wheelchairs, zimmer
      frame, temporary shoes, ortho wedge shoes like rocker-bottom wedge design shoes
      and total contact casting to offload these wounds [3, 4, 5].

PMID- 23133225
TI  - Primary hyperparathyroidism: A report of two unusual cases.
AB  - Primary hyperparathyroidism (PHPT) has a variable clinical expression. Majority
      of the patients are asymptomatic. Symptomatic PHPT with classical skeletal,
      renal, abdominal and neuro-psychiatric manifestations have become exceedingly
      rare. Asymptomatic maternal PHPT manifesting as neonatal hypocalcaemic
      convulsions is another rare entity. The commonest cause of PHPT are solitary
      parathyroid adenomas. These benign tumors are extremely small being difficult to
      identify even at surgical exploration. Very large tumors known as giant adenomas
      are uncommon. Double parathyroid adenomas account for only a small percentage of
      the lesions associated with PHPT. Considerable debate exists as to whether double
      adenomas are a distinct entity or represent early stages of four gland
      hyperplasia. We report two interesting cases of PHPT with classical features,
      that have become rare today such as nephrolithiasis, nephrocalcinosis, and X-ray
      findings of bone disease, caused by unusual pathological lesions like double and
      giant adenomas and discuss rare presentations like neonatal convulsions.

PMID- 23133226
TI  - Extragonadal germ cell tumour.
AB  - We report a rare case of extragonadal germ cell tumour in a 55-year-old man. He
      presented with a painless mass in right inguinal region, a few days after
      hernioplasty for right direct inguinal hernia, which caused diagnostic
      difficulties and treatment problems.

PMID- 23133227
TI  - The ileosigmoid knot.
AB  - Ileosigmoid knot is rare yet life-threatening condition caused by acute double
      loop intestinal obstruction. Preoperative diagnosis is difficult and it is
      associated with high morbidity and mortality. We present one such patient we
      encountered and outline our management, and discuss the surgical options
      available.

PMID- 23133228
TI  - Fibroadenoma of the ectopic breast of the axilla.
AB  - Polymastia is a term that is used to describe the presence of more than two
      breasts in human beings. It is synonymous with supernumerary or accessory breast
      tissue. Ectopic breast tissue (EBT) may occur any where along the primitive
      embryonic milk lines, which extend from the axilla to the groin, and may occur
      unilaterally or bilaterally. In the EBT any disease can develop that affects the
      normal breast, including fibroadenoma. Since publications describing this anomaly
      are rare, we decided to report a case of fibroadenoma in axillary breast tissue.

PMID- 23133229
TI  - Is hyperaldosteronism a pathognomonic feature of conn's syndrome?
AB  - A 10-year-old female child presented with resistant hypertension and
      hypokalaemia. There was no muscle weakness or periodic paralysis. The ratio of
      plasma aldosterone concentration to plasma renin activity was increased. MRI of
      the abdomen showed the right adrenal mass. The child underwent open right
      adrenalectomy. she had natriuresis in the postoperative period. She was
      normotensive without antihypertensive drugs at discharge and 2 months after
      surgery.

PMID- 23133230
TI  - Intestinal lymphangiectasia - a report of two cases.
AB  - Intestinal lymphangiectasia is a rare benign disease characterised by focal or
      diffuse dilation of the mucosal, submucosal and subserosal lymphatics.
      Clinically, the patients may present with protein losing enteropathy (PLE),
      hypoproteinemic oedema, chylous ascites, pleural effusion, acute appendicitis and
      intestinal obstruction.

PMID- 23133231
TI  - Inflammatory myofibroblastic sarcoma of the spermatic cord.
AB  - Inflammatory myofibroblastic tumours are rare clinical presentations and are
      often mistaken for a malignant neoplasm. They can arise from various organs,
      mainly in children and young adults and most commonly from the urinary bladder.
      Paratesticular tissues including spermatic cord are uncommon sites for these
      tumours. In those arising from the paratestis, wide excision usually including an
      orchidectomy is the treatment of choice. A rare such tumour in a 64-year-old
      patient is reported here.

PMID- 23133232
TI  - Unusual case of a projecting intraoral giant sialolith.
AB  - Sialolithiasis is the most common disease of the salivary glands. This report
      describes the case of a patient who had an unusually large submandibular gland
      ductal sialolith that had protruded out into the oral cavity.

PMID- 23133233
TI  - Solid pseudopapillary tumour of pancreas: A rare neoplasm.
AB  - Solid pseudopapillary tumour (SPT) is the rare tumour of pancreas with unknown
      aetiology and good prognosis. Occurs predominantly in young women of reproductive
      age group. Not many cases have been reported from India. We report a case of a
      young woman who presented with persistent back pain having large tumour of body
      of pancreas treated successfully by left pancreatectomy.

PMID- 23133234
TI  - Solid pseudopapillary tumor of pancreas.

PMID- 23133235
TI  - Pyloric Pseudodiverticulum: A rare incidental finding during the repair of
      perforated duodenal ulcer.

PMID- 23133236
TI  - Gastric volvulus.

PMID- 23133237
TI  - Wirsungocele.

PMID- 23133238
TI  - The incidence of soft tissue sarcoma in Dakshina Kannada: Study in a district
      government hospital.

PMID- 23133239
TI  - Extended pancreatectomy for pancreatic cancers.

PMID- 23133240
TI  - Syndromic rhyme.

PMID- 23133242
TI  - Doing less and less: Continuing evolution towards a less invasive approach to
      infected pancreatic necrosis.

PMID- 23133241
TI  - Hippocratic oath, 21st century.
AB  - Hippocratic Oath was first promulgated in 400 BC. Since then it became mandatory
      to take this oath for any medical profesional who practices medicine. The Oath
      envisaged all the important guidelines required to be possessed before the
      medicine is practiced. Recently there had been debates over the traditional oath
      and various revisionist versions were recommended. The enormous available
      literature compells us to think and revisit the status of orignal oath vis a vis
      the practice of medicine in 21st Century.This theme is a part of Dr. KL Wig
      Oration of National Academy of Medical Sciences, delivered at Ahmedabad in
      December 2005.

PMID- 23133243
TI  - Cytologic diagnosis of gallbladder lesions - A study of 150 cases.
AB  - AIMS AND OBJECTIVES: Gallbladder (GB) carcinoma is among the five most common
      forms of gastrointestinal cancers and the diagnosis is usually made when the
      carcinoma is already in an advanced stage. The aim of this study was to assess
      the application of ultrasound (US) guided fine needle aspiration (FNA) in
      diagnosing GB carcinoma. MATERIAL AND METHODS: The present study was carried out
      on 150 patients suspected to have GB carcinoma on ultrasonography. US-guided FNA
      from GB was done in these patients and FNA of the other organs was simultaneously
      done in 20 patients. Histopathology of the GB was available in 14 cases. RESULTS:
      Ultrasonography in these patients revealed mass/thickening of the wall of GB in
      140 (93.3%) cases and nonspecific US findings in 10 (6.7%). Out of the 140 cases
      malignancy was cytologically diagnosed in 105 (75%) cases while 12 (8.5%) cases
      were inflammatory and 23 (16.5%) were inconclusive. Adenocarcinoma was the most
      common morphologic type. Metastatic tumor deposits were noted in FNA from space
      occupying lesions of the liver in 12 cases, abdominal lymph nodes in 5 cases, and
      1 case each of supraclavicular lymph node, stomach and bilateral ovaries. Of the
      10 cases with non-specific US findings, 3 had carcinoma and 7 were inconclusive
      on cytologic examination. CONCLUSION: US guided FNA provides a rapid and reliable
      diagnosis in cases of GB carcinoma.

PMID- 23133244
TI  - Open common bile duct exploration without T-tube insertion- two decade experience
      from a limited resource setting in the Caribbean.
AB  - PURPOSE: Despite advancements in gallbladder surgery with the introduction of
      endoscopic and laparoscopic techniques, many surgeons, especially in the
      developing world, still perform open cholecystectomy with common bile duct (CBD)
      exploration for choledocholithiasis. The purpose of the study is to report the
      outcomes of a case series of open CBD exploration without the use of T-tubes.
      MATERIALS AND METHODS: A retrospective chart review of all consecutive open CBD
      exploration done by the first author over a period of 23 years was conducted.
      Demographic data, preoperative investigations, the surgical techniques and
      perioperative outcomes were recorded. RESULTS: Of 690 open cholecystectomies
      performed during the study period, 108 had common bile duct exploration. In 94
      cases this was done via a supraduodenal choledochotomy, in 10 cases via a
      transduodenal sphincteroplasty and in 4 cases via the cystic duct. In 90 cases, a
      simple choledochotomy and primary closure was done while in 4 cases choledocho
      duodenostomy was required. Eighty-seven percent of surgeries were done on
      elective basis and 13% on an emergency basis and no T-tubes were used in any
      patients. The mean hospital length of stay was 3.2 days and the perioperative
      morbidity was negligible. CONCLUSIONS: In a limited resource setting, there is
      still a role for open CBD exploration and primary closure without the necessity
      of T-tubes and stents as evidenced by a good perioperative patient outcome.

PMID- 23133245
TI  - Hepatic trauma management and outcome; Our experience.
AB  - BACKGROUND: Injuries to the liver have been reported in 35-45% of patients with
      significant blunt abdominal trauma. Since the introduction of ultrasonography and
      computerized tomography in the evaluation of these patients, there has been an
      increase in number of hepatic injuries diagnosed that previously would not have
      been apparent. AIMS AND OBJECTIVES: The purpose of this study was to determine
      the epidemiology and pattern of isolated liver injury, significant factors
      related to management and outcome. MATERIAL AND METHOD: A retrospective study of
      50 cases of isolated Hepatic trauma admitted and managed over span of last three
      years (June 2006-June 2009) at MGM Medical College, Navi Mumbai. OBSERVATION: Out
      of 50 Patients of isolated liver injury, 36 (72%) were managed conservatively.
      14(28%) Patients with refractory hypotension and hemoperitoneum were operated in
      emergency. The mortality of 3 (6%) cases was related to massive bleeding from
      liver parenchyma. CONCLUSION: The line of management of isolated liver trauma is
      primarily guided by the haemodynamic status of the patient at the time of
      presentation in emergency department and findings on ultrasonography [FAST] and
      computerized tomography. There is significant association of line of management
      with volume of hemoperitoneum and number of blood transfusion.

PMID- 23133246
TI  - Analysis of procedure-related complications after pancreatodoudenectomy.
AB  - PURPOSE: To analyze the procedure-related complications after
      pancreaticoduodenctomy (PD) and their risk factors. METHODS: One hundred twenty
      six patients underwent pancreatoduodenectomy for diseases at region of pancreatic
      head were reviewed retrospectively. RESULTS: The overall surgical morbidity was
      40.5% (51/126). Ten (7.9%) of 51 patients were identified as having pancreatic
      leakage, others included delayed gastric emptying (8.7%, 11), abdominal infection
      and abscess (7.9%, 10), abdominal bleeding (5.6%, 7), wound infection (4.8%, 6),
      wound dehiscence (2.4%, 3), biliary fistula (1.6%, 2) and operative death (1.6%,
      2). Other postoperative complications were lung inflammation (3.9%, 5) and newly
      developed diabetes mellitus (2.3%, 3). Age (>60 years), coexisting diabetes
      mellitus, small main pancreatic duct (<=0.5 cm), and surgeon's experience (<10
      patients within 5 years) were demonstrated to be independent risk factors by both
      univariate and multivariate analysis (p < 0.01). CONCLUSIONS: Old patients with
      coexisting diabetes mellitus and small main pancreatic duct undergo
      pancreatoduodenectomy by a less experienced surgeon may be at high risk of
      procedure-related complications.

PMID- 23133247
TI  - The value of resection of primary tumor in gastric cancer patients with liver
      metastasis.
AB  - PURPOSE: Surgery for gastric cancer with synchronous liver metastasis is applied
      for palliation. The aim was to determine whether surgical removal of the primary
      tumor provides a better survival and disease progression METHODS: Sixty-two
      patients are classified according to the primary tumor were removed or not.
      Patients and tumor characteristics, removal of the primary tumor are examined as
      the factors that were affecting overall survival and metastatic progression-free
      survival. RESULTS: The mean follow-up time was 243+/-23 days. The mean survival
      of the resection and nonresection groups were 422+/-50 and 170+/-16 days (p =
      0.0001), respectively. After adjustment for other covariates, resection was
      associated with a trend toward improvement in overall survival (p = 0.003;
      relative risk RR: 0.34; 95% confidence interval (CI): 0.17-0.66) and improvement
      in metastatic progression-free survival (p = 0.07, RR = 0.51; 95% CI: 0.25-1.07).
      CONCLUSIONS: Excision of the primary tumor has an effect on metastatic
      progression-free survival and overall survival.

PMID- 23133248
TI  - Non tuberculous mycobacteria in surgical wounds- a rising cause of concern?
AB  - INTRODUCTION: The non-tuberculous mycobacteria (NTM) have emerged as important
      opportunistic pathogens in the recent years. The NTM are rapid growing
      mycobacteria (RGM), which include Mycobacterium fortuitum and M. chelonae and are
      grouped as M. fortuitum-chelonae complex. Non-healing postoperative wound
      infections that do not respond to antibiotics used for pyogenic infections and
      having sterile routine aerobic cultures should raise a suspicion of NTM. PATIENTS
      AND METHODS: All patients with post operative wound infection over a five year
      period were included in the study. All wound infections were evaluated with wound
      culture and sensitivity and treated with appropriate antibiotics. All infections
      with underlying mesh were initially managed with dressings/debridement, long term
      antibiotics. Explantation of the mesh was to be used as a last resort. RESULTS:
      We analyzed the records of patients with post operative wound infections who had
      wound cultures taken and found that 16 of our patients had initial sterile
      cultures. In all these cases, wound infection manifested itself as discharging
      sinuses between 2-3 weeks after surgery. Of these seven patients grew NTM on
      their repeat cultures. The commonest organism isolated was M. fortuitum (57%).
      The commonest antibiotic used for treatment was Tab Clarithromycin and the mean
      duration of treatment was 6 to 9 months. No patients required debridement or
      removal of mesh. DISCUSSION: NTM infections in post operative wound though rare
      should be suspected in all post operative wound infections which occurs late,
      lack local and systemic signs of pyogenic infections and have sterile cultures.
      High index of suspicion for NTM infection will allow identification and treatment
      of these patients with long-term antimicrobial therapy alone without the need for
      surgical explantation of the mesh.

PMID- 23133249
TI  - Impact of obesity on urologic complications among unrelated living donor kidney
      transplants.
AB  - PURPOSE: Although obesity has been associated with improved survival on dialysis,
      its effects on renal transplantation outcomes remain unclear. Herein we aimed to
      evaluate the effect of obesity on posttransplantation complications. PATIENTS AND
      METHODS: A retrospective analysis of consecutive renal transplant recpients from
      un related living donors was undertaken from 2006 to 2008. RESULTS: We included
      180 patients, 34 (18%) were obese (body mass index >30 kg/m(2)) and 146 were
      lean. Obese patients were more likely to develope renal artery stenosis (17.6% vs
      2.8%, p < 0.001), hematoma (47.9% vs 17.6, p = 0.009), wound complications (64.7%
      vs 9.6%, P < 0.001) and renal vein thrombosis(2% vs 0%, p < 0.001). Urologic
      complications consisting ureteral, ureteropelvic and ureterovesicular junction
      stenosis, wound bleeding, urinary leakage and renal artery thrombosis and also
      hospitalization time were found similar between the two groups. 2 year patiets
      and graft survival were not statististically different. CONCLUSIONS: Renal
      transplantation could be performed with reasonable urologic complications in
      obese patients.

PMID- 23133250
TI  - Clinically monitored delay-A valid option in cases with doubtful diagnosis of
      acute appendicitis.
AB  - AIM: To evaluate the effect of delayed surgery after a period of observation in
      patients with doubtful diagnosis of acute appendicitis in the form of improvement
      in negative appendectomy rates and the incidence of complications. MATERIALS AND
      METHODS: One hundred twelve patients operated with the diagnosis of acute
      appendicitis between May 2008 to June 2009 were included in this retrospective
      study. They were divided into two groups based on timing of surgery after
      admission. These two groups were studied in respect to age, sex, Alvarado score
      at presentation, ultrasound findings, operative findings, histopathology and
      postoperative complications. Proportions of negative appendectomies, and
      complicated appendicitis were analysed statistically. RESULTS: Group wise age and
      sex distribution was comparable. The mean Alvarado score in the group 1 was 7.9
      (range, 6-10) where as in those operated later than 12 hours (group 2), it was
      4.5 (range, 3-8). Normal appendectomies were significantly (p < 0.05) less in
      group 2 (1 out of 40) as compared to group 1 (4 out of 72). The number of
      complicated appendicitis were higher in group 1 (14/72) as compared to group 2
      (4/40) but not significantly (p > 0.06). The number of postoperative
      complications was also high in group 1 (11 vs 2 in group 2). CONCLUSION: It is
      better to wait in cases with doubtful initial diagnosis of appendicitis on
      admission in order to decrease negative appendectomy rates. These patients need
      to be continuously monitored clinically to prevent complications.

PMID- 23133251
TI  - Residual gallstone disease - Laparoscopic management.
AB  - BACKGROUND: A few patients who continue to suffer antecedent symptoms following
      laparoscopic cholecystectomy (LC) may harbor residual gallstones. The incidence
      of residual gallstones following cholecystectomy is <2.5%. Many of these patients
      require a completion cholecystectomy to ameliorate their symptoms. MATERIALS AND
      METHODS: We reviewed our experience of laparoscopic re-intervention for residual
      gallstones over a period of 10 years from January 1998 to December 2007. Twenty
      six patients underwent Laparoscopic completion cholecystectomy (LCC) for residual
      gallstone disease. Twelve patients had a previous LC (2 patients - subtotal
      cholecystectomy) and 9 patients had a previous open cholecystectomy (7 patients -
      subtotal cholecystectomy). Five patients had previously undergone a
      cholecystostomy. Diagnostic investigations included abdominal ultrasound,
      endoscopic ultrasound (EUS), magnetic resonance cholangio-pancreatography (MRCP)
      and endoscopic retrograde cholangio-pancreatography (ERCP). RESULTS: Findings
      included a remnant gallbladder in 3 patients, long cystic duct stump with
      impacted stone in 18 patients and a contracted gallbladder in 5 patients. All
      procedures were successfully completed laparoscopically. The mean operative time
      was 62 minutes and mean blood loss 50cc. Ten patient required abdominal drains
      postoperatively. Two patients had bilious drainage lasting 9 days and 11 days
      respectively. One patient died a week following surgery of acute myocardial
      infarction. Another patient died 6 months later of unrelated causes. The
      remaining patients have remained symptom free at a mean follow up of 3.2 years
      (range 7 months to 9 years). CONCLUSION: The possibility of residual gallstones
      increases with subtotal cholecystectomy and inadequate dissection of the Calot's
      triangle in the presence of acute inflammation. Laparoscopic re-intervention for
      treating residual gallstone disease is feasible and can be safely performed in
      centers of expertise.

PMID- 23133252
TI  - Comparison of the adherence of E.Coli and S. Aureus to ten different prosthetic
      mesh grafts: In vitro experimental study.
AB  - BACKGROUND: The prosthetic mesh grafts used to repair the abdominal wall may
      become infected, primarily by S. aureus and E. coli. This study sought to provide
      a rational basis for the choice of mesh used to repair a hernia when there is a
      likelihood of infection or contamination. METHODS: S. aureus and E. coli were
      incubated with ten types of prosthetic mesh graft (Table 1) in liquid growth
      medium. After sequential dilution of samples from the prosthetic mesh grafts, the
      colony forming units of adherent S. aureus and E. coli were counted. RESULTS:
      There was no significant difference in the numbers of E. coli and S. aureus
      adherent to simple polypropylene mesh grafts. Significantly more of both species
      were adherent to the polyester, expanded polytetrafluoroethylene (ePTFE), and
      composite prosthetic mesh grafts, except for E. coli on graft 5. Significantly
      fewer E. coli were adherent to composite mesh grafts 5, 8, and 10 than S. aureus.
      CONCLUSION: S. aureus and E. coli adhere to polypropylene similarly. In vitro,
      fewer S. aureus and E. coli adhere to simple polypropylene mesh grafts than to
      polyester, ePTFE, or composite prosthetic mesh grafts.

PMID- 23133253
TI  - Trauma of facial skeleton in children: An indian perspective.
AB  - AIMS: Both children and adults are subject to similar types of injuries but
      fractures of facial bones in children are relatively uncommon. The aim of this
      study was to evaluate the epidemiology of facial bone fractures among children of
      <12 years, their management and outcome in an Indian city. MATERIAL AND METHODS:
      This retrospective study included children of <12 years of age with facial bone
      fractures admitted over a span of 3 years. In order to compare our results we
      reviewed the existing literature related to pediatric facial bone fractures.
      RESULTS: A total of 45 children were admitted for facial bone fractures. Forty
      (89%) of them were above 5 years of age and male to female ratio was 2:1. About
      53.33% of these injuries were because of fall from height. Mandible fracture was
      the most common facial bone fracture among admitted patients. Symphysis and para
      symphysis was the commonest site of mandibular fractures, seen in 49% cases.
      Majority of these fractures were managed by Inter-maxillary fixation and inter
      osseous wiring. Mini-plates were used for widely displaced compound fractures.
      For un-displaced fractures observation alone was sufficient. CONCLUSION: Mandible
      is the commonest facial bone fracture in children, more often caused by
      accidental fall from height. The high osteogenic potential of pediatric mandible
      allows non-surgical management to be successful in an increased proportion of
      younger patients.

PMID- 23133254
TI  - Uncut Roux-en-y esophagojejunostomy: A new reconstruction technique after total
      gastrectomy.
AB  - PURPOSE: Uncut Roux-en-y is a reconstruction method with a main purpose of
      diminishing Roux stasis syndrome. In this study we performed this procedure to
      evaluate utility and complications of this technique, as well as its effect on
      Roux stasis syndrome. METHODS: Total gastrectomy with Uncut Roux-en-y
      esophagojejunostomy was performed on 94 patients. This technique consists of an
      artificial jejunal occlusion 5 cm proximal to anastomosis and a jejunojejunostomy
      between afferent and efferent loops. Diagnosis of "Roux stasis syndrome" was made
      by clinical criteria. RESULTS: According to the mentioned criteria, the "Roux
      stasis syndrome" occurred in 21.2% of the patients. Whereas occurrence rate of
      other complications was: dysphasia (13.8%), benign stricture in anastomosis
      (9.6%), and fistula (5.3%). CONCLUSIONS: Comparing the results of our study to
      other related studies indicates that this type of operation has lower rate of
      "Roux stasis syndrome", and also decreases the postoperative stricture rate of
      the anastomosis.

PMID- 23133255
TI  - Prophylactic antibiotic usage in patients undergoing inguinal mesh hernioplasty -
      A clinical study.
AB  - BACKGROUND: There is ambiguity about the use of antibiotic prophylaxis in
      inguinal mesh hernioplasty. We have tried to assess the efficacy of antibiotic
      prophylaxis in this procedure. MATERIALS AND METHODS: A randomized double blind
      placebo controlled study was conducted which included 55 patients who underwent
      an inguinal mesh hernioplasty over a 2 year period. The patients were evaluated
      for the status of the suture line as well as the presence of wound infection.
      RESULTS: Out of 55 patients 29 were randomized to the antibiotic arm and 26 to
      the placebo group. The groups were well matched for all variables studied
      excluding wound infections, which occurred at a rate of 10.34% (n = 3) in the
      antibiotic group and 15.38% (n = 4) in the placebo arm, (p > 0.01). CONCLUSION:
      This study did not document any statistically significant difference observed
      between those who received antibiotics and those receiving placebo in terms of
      any of the prognostic end points evaluated for Lichtenstein mesh hernioplasty.

PMID- 23133256
TI  - Negative prognostic factors in colorectal carcinoma: An analysis of 448 patients.
AB  - BACKGROUND AND AIMS: Colorectal carcinoma (CRC) is the most frequent malignancy
      of the gastrointestinal tract. Prognostic researches are carried out for choosing
      the optimum therapy, evaluating therapy results and comparing multicentre results
      for better qualification in the therapy of the disease. PATIENTS AND METHODS: In
      this study, 448 patients, whose surgery and follow-up was performed by the same
      correspondent surgeon between the years 1995 and 2003, were retrospectively
      analyzed. RESULTS: Age, presence of comorbidity, weight loss, emergency
      admission, high serum CEA and CA 19-9 levels, neighboring organ invasion,
      operation type, major morbidity, tumor size and type, lymph node metastases,
      venous and perineural invasion, Dukes' classification and local recurrence and
      distant metastasis during follow-up are found to be significant negative factors
      affecting prognosis of the CRC patient. CONCLUSION: Therapy results of the CRC
      are evaluated by survival times regardless of the therapy method selected for
      each individual. In our study we tried to find out negative prognostic factors by
      researching possible factors affecting disease free survival time for CRC. Since
      our understanding of factors that have an impact on prognosis increases, we are
      hoping to improve survival.

PMID- 23133257
TI  - Ultrasound guided foam sclerotherapy for varicose veins using two needle
      technique - A case series.
AB  - INTRODUCTION: Varicose veins are one of the most common vascular problems
      encountered. Ultrasound guided foam sclerotherapy is one such option it was
      introduced in 2001. We present our two needle technique of ultrasound guided foam
      sclerotherapy along with our short term results. MATERIALS AND METHODS: Patients
      presenting us between January 2009 to October 2009 with symptomatic primary
      varicose veins were selected for this procedure. Ultrasound guided foam
      sclerotherapy was done using the two needle technique using sodium tetra decyl
      sulphate. RESULTS: Fifteen patients and 19 legs were treated. Complete closure of
      veins was achieved with a single injection at 1 month follow up in 17 legs. One
      leg required one additional injection and one leg required two injections. No
      recurrence has been noted at the end of a follow up of 1-6 months. CONCLUSION:
      Foam sclerotherapy is an effective, less expensive day care procedure with
      minimal complication rates.

PMID- 23133258
TI  - Thoracoscopic retrieval of intra-parenchyamal foreign body of lung.
AB  - Thoracoscopy is an innovative procedure. We have retrieved intraparynchymal lung
      foreign body by thoracoscopy. Intraoperative imaging by 'C' arm facilitated the
      procedure. Thoracoscopy is a therapeutic option of choice for projectile thoracic
      injuries, provided patient is hemodynamically stable.

PMID- 23133259
TI  - Diaper ileostomy appliance.
AB  - Ileostomy complications relating to surrounding skin are common when it is
      constructed with the proximal ileum, due to the irritative nature of the
      effluent, and ill fitting appliances. I report an improvised ileostomy appliance
      using a diaper, to treat the skin excoriations, which should be useful in
      situations where surgeons do not have an option other than creating a proximal
      ileostomy at an unconventional site.

PMID- 23133260
TI  - Gloves as a teaching tool in vascular surgery.
AB  - Training and practice are essential aspects of keeping surgical skills sharp. We
      present a technique where we use latex gloves as a reliable, easily available,
      inexpensive tool to train surgeons in vascular surgery.

PMID- 23133261
TI  - Giant congenital infected splenic cyst: An interesting case report and review of
      the literature.
AB  - Splenic cysts are rare lesions. The congenital non-parasitic cysts of the spleen
      are rarely met in the clinical practice. Primary cysts have a cellular lining
      that can be caused by congenital events or parasitic infection (Echinococcus).
      Secondary cysts have no cellular lining and may be of hemorrhagic, serous,
      inflammatory, or degenerative origin. We report a rare case of congenital cyst of
      spleen in a child aged 10 years treated successfully by splenectomy because of
      total involvement of the splenic parenchyma along with involvement of hilum by
      the cyst, and we review the literature.

PMID- 23133262
TI  - Pleomorphic hyalinizing angiectatic tumor of soft parts involving the upper limb.
AB  - Pleomorphic hyalinizing angiectatic tumor (PHAT) of soft parts is a low grade,
      rare, soft tissue tumor which commonly occurs on the lower extremities of adults
      of either sex, though lesions in other anatomic locations have been described. We
      present a case of a 65-year-old female patient who presented with a left forearm
      swelling and underwent a wide local excision. Histopathology revealed it to be a
      PHAT.

PMID- 23133263
TI  - Superior mesenteric artery syndrome secondary to brucellosis - A case report.
AB  - Superior mesenteric artery (SMA) syndrome is a rare condition characterized by
      duodenal obstruction due to extrinsic compression by SMA. Any condition which
      results in rapid, significant weight loss can cause SMA syndrome. Brucellosis is
      a common cause of pyrexia of unknown origin which can result in loss of appetite
      and weight loss. Brucellosis resulting in SMA syndrome has not been described in
      literature. We present a case of SMA syndrome resulting from weight loss due to
      brucellosis along with a brief review of relevant literature.

PMID- 23133264
TI  - Congenital transmesenteric internal hernia - A case report with literature
      review.
AB  - Congenital transmesenteric internal hernia is a rare condition presenting as
      recurrent pain abdomen or acute intestinal obstruction. Preoperative diagnosis of
      internal hernia is very rare. Early intervention and surgical correction goes a
      long way in preventing high morbidity and mortality associated with cases of
      internal hernia. We report a case of congenital transmesenteric intra-abdominal
      hernia presented as acute abdomen with timely surgical intervention in the form
      of emergency laparotomy with untwisting and reduction of small bowel herniated
      through large congenital terminal ileal mesenteric defect and repair of
      mesenteric defect.

PMID- 23133265
TI  - Duplication cyst of the cecum: A case report.
AB  - Duplication of alimentary tract is one of the rare congenital anomalies. A case
      of duplication cyst of the cecum, presented in the 3rd month of life, as
      intestinal obstruction. Excision of the cyst along with cecum and appendix was
      done. The child had an uneventful postoperative recovery following ileoascending
      anastomosis.

PMID- 23133266
TI  - Perforated subhepatic appendix presenting as gas under diaphragm.

PMID- 23133267
TI  - Giant vesical calculus of 1125 grams in an Indian.

PMID- 23133268
TI  - Results of breast conserving surgery in clinical stage I-II breast carcinoma.

PMID- 23133269
TI  - Responsible writing.

PMID- 23133270
TI  - Cost of a purge: Enema induced perianal gangrene.

PMID- 23133271
TI  - A rose by any other name - Hasson's technique and its modifications.

PMID- 23133272
TI  - Primary cutaneous CD 30+ anaplastic large cell lymphoma.
AB  - Cutaneous T cell lymphoma (CTCL) is a broad diagnostic group encompassing a
      spectrum of diseases with variable clinical presentations. Histologic and
      immunohistochemical confirmation is needed to establish a precise diagnosis.
      Primary cutaneous CD 30+ anaplastic large cell lymphoma, a definite variety of
      CTCL, presenting as a non-healing ulcer is presented here which, needed
      multimodality approach to heal.

PMID- 23133273
TI  - Primary leiomyosarcoma of the breast: A case report and review of literature.
AB  - Leiomyosarcomas of the breast are rare tumours. Only 18 such cases have been
      reported in the literature so far. We describe herein a case of primary
      leiomyosarcoma of the breast in a 54-year-old woman whose preoperative clinical
      and cytological findings indicated a benign breast tumour. However, a core needle
      biopsy of the lesion showed malignant spindle cells without any ductal elements.
      Histopathological examination of the mastectomy specimen suggested a diagnosis of
      leiomyosarcoma, which was subsequently confirmed by immunohistochemical analysis.
      Primary leiomyosarcoma of the breast is very rare and is difficult to diagnose
      preoperatively as it needs immuno-histochemical staining. It is necessary to
      excise the tumour with sufficient margins to prevent local recurrence. The role
      of postoperative adjuvant chemotherapy is not well documented.

PMID- 23133274
TI  - Unusual presentation for primary appendiceal lymphoma: A case report.
AB  - Primary appendiceal neoplasms are uncommon, being found in approximately 0.5%
      1.0% of appendectomy specimens at pathologic evaluation. Primary appendiceal
      Burkitt's lymphomas are rare occurring in 0.015% of all gastrointestinal
      lymphomas. Almost all reported cases of appendiceal lymphoma have proved to be
      non-Hodgkin lymphoma. The majority of appendiceal lymphomas are of B-cell.
      Patients were almost entirely males. Acute appendicitis is the most common
      clinical manifestation. This report describes a rare case of primary appendiceal
      lymphoma in a patient presented with hematuria and dull aching right lower
      abdominal and back pain.

PMID- 23133275
TI  - Synovial sarcoma of anterior abdominal wall.
AB  - Sarcomas are connective tissue tumours, and can arise in any part of the body,
      more commonly in the extremities. Histological types and clinical presentation of
      truncal sarcomas are similar to those seen in any other anatomic locations.
      Radiological investigations may be contributory, but biopsy is conclusive.
      Surgical resection with wide margins is the initial standard treatment, however a
      multimodal approach including radiotherapy and chemotherapy is often favoured.
      Because of the high recurrence rate regardless of therapy, close follow-up is
      imperative. We present a case of synovial sarcoma of the anterior abdominal wall.

PMID- 23133276
TI  - Pancreatic schwannoma: Report of a case and review of literature.
AB  - Connective tissue tumors of pancreas are uncommon, among them pancreatic
      schwannoma is very rare tumor, very few cases were reported in literature.
      Aggressive resections like whipple's procedure, or distal pancreatectomy are not
      necessary for pancreatic schwannoma as it rarely goes to malignant change and
      simple enuclation is sufficient.In our patient pancreatic schwannoma is
      associated with simple cyst in liver and absence of one kidney. Here, we are
      presenting a case of pancreatic schwannoma treated by simple enucleation.

PMID- 23133277
TI  - Obturator hernia of the Richter type: A case report.
AB  - Obturator hernia is a rare type of hernia which accounts for only 0.07-1.4% of
      all intra-abdominal hernias and 0.2-5.8% of small-intestinal obstructions.
      Because the symptoms are non-specific, the diagnosis is often delayed until
      laparotomy is performed to treat bowel obstruction. The need for awareness of the
      condition is stressed, and the diagnosis of obturator hernia should be strongly
      suspected in a thin, elderly woman who has small bowel obstruction and no
      previous abdominal surgery. Here is a case report of obturator hernia in which
      the diagnosis was difficult because of the slow development of symptoms; on
      laparotomy it was found to be a Richter hernia. Computed tomography scanning can
      be helpful and will typically show an incarcerated small bowel behind the
      pectineus muscle. Laparoscopy may be necessary for diagnosis, and the hernia can
      be repaired laparoscopically.

PMID- 23133278
TI  - Gluteal region musculoskeletal hydatid cyst: Case report and review of
      literature.
AB  - Hydatid disease is a parasitic infestation of humans and herbivorous animals,
      caused by Echinococcu granulosus. Dogs and some wild carnivores, like foxes, are
      definitive hosts, harboring worms in their intestines. Musculoskeletal cysts
      account for 0.7-3% of total cases of hydatidosis. Primarymuscular hydatidosis
      without involving the thoracic or abdominal organs is extremely rare.
      Intramuscular infestation may mimic a soft tissue tumor leading to inappropriate
      cyst rupture with the attendant risks of anaphylaxis and dissemination to other
      organs. So preoperative evaluation is critical to avoid lifethreatening
      complications. We report a case of 34-year-old male patient with a cystic gluteal
      swelling turning out to be hydatid cyst on surgical exploration. Surgical
      excision with a pharmacology complementary treatment with antihelementhics is
      necessary to achieve the complete healing.

PMID- 23133279
TI  - Primary mucormycosis of abdominal wall: A rare fungal infection in a
      immunocompetent patient.
AB  - Mucormycosis of the anterior abdominal wall is an uncommon disease and it is very
      rare to find this disease in immunocompetent, non-diabetic patients which usually
      affects patients with trauma, with contaminated wounds, patients with underlying
      malignancies or patients with immunocompromised state, e.g., diabetics. We herein
      report a case of primary cutaneous mucormycosis in an immunocompetent and non
      diabetic patient. Our patient was a 48-year-old female, executive by profession.
      She was diagnosed to have cutaneous mucormycosis of the anterior abdominal wall,
      and was managed with multiple debridements of the wound and intravenous
      amphotericin B therapy. She was administered a total of 1500 mg of liposomal
      amphotericin B and when fully healed, split skin grafting was done. We would like
      to emphasize the importance of high index of suspicion and early start of therapy
      in a condition with high rate of mortality.

PMID- 23133280
TI  - Pre-expanded epigastric flap cover for ventral hernia following fungal
      necrotizing fascitis of caesarian section wound: An unusual complication.
AB  - INTRODUCTION: Reconstruction of anterior abdominal wall after necrotizing
      abdominal wall infections is a challenge. MATERIAL AND METHODS: A 35-year-old
      lady presented with 20 * 18 cm sized defect of the anterior abdominal wall
      following fungal necrotizing fascitis. The defect was covered by an overlay
      prolene mesh and the soft tissue deficit was corrected by pre-expanded epigastric
      flap based on the superior epigastric artery. CONCLUSION: A concerted multi
      specialty effort is needed to correct these defects.

PMID- 23133282
TI  - Endometriosis of the appendix: A diagnostic dilemma.
AB  - The incidence of endometriosis of the appendix is reported to be just <1% of the
      total endometriosis cases. Laparoscopic visualization and diagnostic yield are of
      profound significance to women in whom gynecologic diseases such as
      endometriosis, pelvic inflammatory disease, ruptured ovarian follicles or tubal
      pregnancy may be the source of pain and mimic appendicitis. Therefore, lower
      abdominal pain in reproductive age group female must invite the attention of the
      surgeon or gynecologist to entertain the possibility of endometriosis since
      appendiceal endometriosis, while relatively uncommon in patients with
      endometriosis, is rare in the general population.

PMID- 23133281
TI  - Tuberculosis nearly preventing a curative resection for colorectal liver
      metastasis: A case report.
AB  - Perihepatic lymph node involvement portends a poor prognosis, and is reported to
      be the most important prognostic factor following R0 resection of colorectal
      liver metastases. Tuberculous lymphadenitis is one of the common presentations of
      tuberculosis and is often diagnosed only after histopathological confirmation. In
      this patient, a frozen section revealing tuberculosis in the perihepatic nodes
      allowed us to proceed with the curative liver resection.

PMID- 23133283
TI  - Giant sublingual epidermoid cyst - An unusual case report.
AB  - Epidermoid cysts of the floor of the mouth represent <0.01% of all oral cysts.
      Only few cases have been reported so far. We report a case of a 24 years man with
      a large sublingual swelling for 17 years, unable to take solid meals. The
      swelling was approximately 13 * 13 cm, non-tender, non-transilluminant, with
      doughy consistency and with patent visible Wharton's duct openings on both the
      sides. Initial decompression of the lesion was done to facilitate nasotracheal
      intubation followed by partial excision of the cyst with marsupialization.
      Histopathological examination revealed a thick wall cyst lined with
      pseudostratified squamous epithelium without any evidence of dermal appendages
      suggestive of epidermoid cyst. Postoperative care included extraction of the
      loose infected dentures and physiotherapy of the ankylosed temporomandibular
      joints. Clinical progress was uneventful and cosmetic appearance was acceptable
      on 6 month and 2 years follow up with normal mastication function.

PMID- 23133284
TI  - Ruptured large carotid artery aneurysm.
AB  - Carotid artery aneurysms are rare [1]. Bifurcation of the common carotid artery
      is most frequently reported site of true aneurysm in the extracranial carotid
      system. Blunt injury of the neck involves high cervical portion of the internal
      carotid artery. Large aneurysms of the carotid artery can distort the anatomy and
      one can anticipate the intubation difficulties during anesthesia induction. A man
      aged 25 years, weighing 35 Kilograms was admitted in emergency with a large
      swelling (bleeding) on the right side of neck, covered with a bandage. In a rural
      hospital, biopsy was attempted, wounds were packed with gauze as there was
      profuse bleeding and referred the patient to our hospital. Spiral CT angiogram
      showed a large aneurysm arising from the bifurcation of the right common carotid
      artery. He complained of dysphagia for the past 20 days. In the CT scan the
      internal carotid artery was found to be occluded without neurological deficit.
      During surgery the common carotid, external carotid arteries were dissected out,
      clamped, ligated and thrombi were evacuated. The unhealthy and inflamed tissues
      were debrided. The wound was closed with a drain. Postoperative recovery was
      uneventful without neurological deficits.

PMID- 23133285
TI  - Neurofibromas of saphenous nerve mimicking thrombophlebitis.
AB  - Young man aged 25 years complained of persistent pain on the medial side of the
      lower part of the thigh for 2 months. A cord like structure was palpable with 3
      small nodular swelling parallel to the course of the long saphenous vein.
      Initially he was treated as a case of thrombophlebitis of saphenous vein in a
      clinic near his home. When the pain persisted after receiving injection heparin
      therapy, he was referred to the vascular surgery clinic. Duplex scan reported as
      thrombophlebitis of a vein parallel to the great saphenous vein. We continued the
      injection heparin and suspected thrombophilia. There were no other known risk
      factors for thrombosis. The pain persisted, so we excised the cord like structure
      with nodular swellings and biopsy reported it as neurofibromatosis of the
      saphenous nerve. Postoperatively the pain subsided dramatically and in the follow
      up clinic he mentioned about the paresthesias in the distribution area of
      saphenous nerve. Diagnosis of the small tumors of the peripheral nerves is
      difficult at this site and they can be easily mistaken for thrombophlebitis.
      Unusual pain and nodularity of the swelling as in this case can help us to
      consider early biopsy or excision of the tumor.

PMID- 23133286
TI  - A case of splenic rupture in patient of situs inversus.
AB  - To the best of our knowledge association of splenic rupture caused by blunt
      trauma in association with situs inversus has not been reported before. There is
      no report of emergency splenectomy for situs inversus before. We are reporting a
      case of splenic rupture caused by blunt trauma in association with situs
      inversus. Preoperative diagnosis of associated congenital heart defects and
      associated anatomical defects is necessary before operation.

PMID- 23133287
TI  - Colonic metastasis from subcutaneous angiosarcoma: A diagnostic dilemma.
AB  - Primary angiosarcoma is an extremely rare and aggressive soft-tissue malignancy
      of endothelial cell origin that occurs most frequently in the skin and
      subcutaneous tissues of the extremities. Presence of this disease in the
      intestine as a primary or metastatic deposit is an extremely uncommon incident,
      and might causes diagnostic confusion with primary colonic neoplasm. We
      encountered epithelioid angiosarcoma of the sigmoid colon in a 59-year-old male
      patient who presented with occasional bleeding per rectum and had also had an
      angiosarcoma arising from the subcutaneous tissue of the right thigh.
      Retrospective review of histopathology and immunohistochemistry of the two
      specimens were helpful in the final diagnosis.

PMID- 23133288
TI  - Meckel's diverticulum with benign stricture: A very rare cause of intestinal
      obstruction.
AB  - We report a very rare case of Meckel's diverticulum with benign stricture
      presenting as recurrent small bowel obstruction in a malnourished young adult
      female. Extensive preoperative investigations were unable to diagnose the cause
      of recurrent obstruction. Segmental small bowel resection with attached
      diverticulum was performed.

PMID- 23133289
TI  - Schwannoma of common bile duct causing obstructive jaundice.
AB  - Benign schwannomas arise from neural crest-derived Schwann cells. Schwannomas
      occurring in the biliary tract become clinically symptomatic due to their
      compression on the extra hepatic biliary tract causing obstructive jaundice.
      Their preoperative diagnosis is extremely difficult. We report a 38-year-old male
      who presented with pain abdomen and jaundice. Computed tomography of abdomen
      showed extra luminal compression of common bile duct (CBD) possibly by a lymph
      nodal mass. Resection of the CBD, gall bladder and the mass compressing the CBD
      with Rouxen-Y hepaticojejunostomy was performed. The final histopathology was
      reported as a schwannoma.

PMID- 23133290
TI  - An unusual case of chest wall desmoid tumor.
AB  - Desmoid tumor of the chest wall are uncommon fibromatous tumors characterized by
      their local invasion and frequent recurrences. Extra-abdominal sites are mainly
      the shoulder girdle, the pelvic girdle and distal ends of the lower limbs. The
      chest wall represents 8-10% of cases and the tumor is exceptionally
      intrathoracic. We present here a rare case of a large desmoid tumor of left
      antero-lateral chest wall. In the presented case, wide excision of the tumor and
      chest wall reconstruction was done. There was no recurrence in 3 years of follow
      up.

PMID- 23133291
TI  - Fournier's gangrene - Not a stigma for surgery with newer surgical reconstruction
      of scrotum.
AB  - A 34-year-old man with complaining of high fever and painful swelling and edema
      of the scrotum was admitted to our hospital. As per clinical and radiological
      findings, he diagnosed as a case of Fournier's gangrene. We started treatment
      with antibiotics, and extensive soft tissue debridement of scrotum done. After
      the debridement, infection was controlled by wound irrigation, higher antibiotic,
      regular dressing. Patient improved drastically and mature granulation covered
      both the testes completely within 14 days. After all this treatment, the
      neoscrotum was made successfully by mobilizing bilateral fascio-cutaneous flaps
      from adjacent supero-medial sites of the thighs. The patient was discharged on
      26th day and patient is doing well in follow up.

PMID- 23133292
TI  - Amyand's hernia with mucinous cysadenoma of the appendix.
AB  - Amyand's hernia is a rare condition in which the appendix is positioned in the
      inguinal hernia sac. Mucinous cysadenoma of the appendix is rather extremely
      rare. We report a case of a mucinous cystadenoma of the appendix which presented
      as an incarcerated right indirect inguinal hernia (Amyand's hernia).

PMID- 23133293
TI  - Intramuscular haemangioma of mylohyoid muscle: A case report.
AB  - OBJECTIVE: To report a case of intramuscular haemangioma (IMH) with a rare
      presentation in the mylohyoid, with emphasis on the clinical appearance, and
      histologic characteristics of the lesion. METHOD: Case report and review of the
      literature. CONCLUSION: Neck swellings can often present a diagnostic dilemma,
      with a wide preoperative differential diagnosis. IMH are rare benign haemangiomas
      occurring within the skeletal muscle. They account for approximately 1% of all
      haemangiomas. These are uncommon in the head and neck region and occur most
      frequently in the trunk and extremities. In the head and neck, masseter and
      trapezius are the most common sites involved. Intramuscular haemangioma is seldom
      diagnosed preoperatively, perhaps due to unfamiliarity with this uncommon lesion
      and nonspecific clinical findings.

PMID- 23133294
TI  - Giant mucocele of appendix as pelvic mass: A rare presentation.

PMID- 23133295
TI  - Colonic obstruction secondary to endometriosis.

PMID- 23133296
TI  - Protruding aneurysm of arteriovenous fistula.

PMID- 23133297
TI  - Pseudomyxoma peritonei.

PMID- 23133298
TI  - Bowen's disease - A skin lesion to look out for in surgical clinics.

PMID- 23133299
TI  - Metaplastic carcinoma breast (carcinosarcoma variant).

PMID- 23133300
TI  - Giant hydronephrosis.

PMID- 23133301
TI  - A giant congenital lipoma over the back.

PMID- 23133302
TI  - Diffuse plexiform neurofibroma.

PMID- 23133303
TI  - Carotid body tumor.

PMID- 23133304
TI  - The world's heaviest ureteric calculus?

PMID- 23133305
TI  - An unusual cause of small bowel obstruction: "The swiss cheese transomental
      hernia".

PMID- 23133306
TI  - Prevalence and risk factors for bacterial vaginosis and other vulvovaginitis in a
      population of sexually active adolescents from Salvador, Bahia, Brazil.
AB  - Bacterial vaginosis, trichomoniasis, and genital candidiasis are considered the
      main etiologies of vulvovaginitis. Few studies estimate the prevalence of
      vulvovaginitis among adolescents, especially in Brazil. This study aimed to
      determine the prevalence and main risk factors associated with bacterial
      vaginosis and genital infection by C. albicans and Trichomonas vaginalis among a
      group of adolescents from Salvador, Bahia, Brazil. One hundred sexually active
      adolescents followed at an adolescent gynecology clinic were included.
      Endocervical and vaginal samples were obtained during gynecological examination.
      Nugent criteria were applied for the diagnosis of bacterial vaginosis. For
      Candida albicans and Trichomonas vaginalis detection, culture in Sabouraud agar
      plates and Papanicolaou cytology were used, respectively. The mean age of
      participants was 16.6 +/- 1.6 years. The prevalence of bacterial vaginosis was
      20% (95% CI 12-28) and of genital infection by Candida was 22% (95% CI 14-30).
      Vaginal cytology detected Trichomonas vaginalis in one patient. Alcohol, tobacco,
      and illegal drug use (P = 0.02) and multiple lifetime partners were statistically
      related to bacterial vaginosis (P = 0.01). The prevalence of bacterial vaginosis
      and genital candidiasis was similar to other studies carried out among
      adolescents worldwide.

PMID- 23133308
TI  - Comparison of First-Order Sorption Kinetics Using Concept of Two-Site Sorption
      Model.
AB  - We compared two different approaches available in the literature for first-order
      sorption kinetics, which constitutes the slow time-dependent part of the two-site
      sorption model commonly used for solute transport. One approach assumes that
      sorbed concentrations in the Type-1 site (S(1)) and the Type-2 site (S(2)) are
      directly associated with a solute concentration (C) in liquid phase by forming
      two-site sorption with a parallel interface; the other assumes that S(2) is
      associated with only S(1) at the Type-1 site, resulting in two-site sorption with
      a serial interface. Application of different kinetics to a batch system where
      solute mass is conserved resulted in an identical type of liquid and sorbed
      concentration versus time equation in the form of exponential decay. However,
      because of the different structure and components used to define the kinetic part
      (S(2)), some parameters estimated from observed kinetic sorption data deviated
      significantly from one another. For instance, the fraction (f) of the Type-1 site
      varied as much as twofold, which led to different transport behavior. This
      indicates that choice of the kinetic part in the two-site sorption model becomes
      important when attempting appropriate transport modeling on reactive solutes.

PMID- 23133307
TI  - Diaphragm used with replens gel and risk of bacterial vaginosis: results from a
      randomized controlled trial.
AB  - BACKGROUND: Bacterial vaginosis (BV) has been linked to female HIV acquisition
      and transmission. We investigated the effect of providing a latex diaphragm with
      Replens and condoms compared to condom only on BV prevalence among participants
      enrolled in an HIV prevention trial. METHODS: We enrolled HIV-seronegative women
      and obtained a vaginal swab for diagnosis of BV using Nugent's criteria; women
      with BV (score 7-10) were compared to those with intermediate (score 4-6) and
      normal flora (score 0-3). During quarterly follow-up visits over 12-24 months a
      vaginal Gram stain was obtained. The primary outcome was serial point prevalence
      of BV during followup. RESULTS: 528 participants were enrolled; 213 (40%) had BV
      at enrollment. Overall, BV prevalence declined after enrollment in women with BV
      at baseline (OR = 0.4, 95% CI 0.29-.56) but did not differ by intervention group.
      In the intention-to-treat analysis BV prevalence did not differ between the
      intervention and control groups for women who had BV (OR = 1.01, 95% CI 0.52
      1.94) or for those who did not have BV (OR = 1.21, 95% CI 0.65-2.27) at
      enrollment. Only 2.1% of participants were treated for symptomatic BV and few
      women (5-16%) were reported using anything else but water to cleanse the vagina
      over the course of the trial. CONCLUSIONS: Provision of the diaphragm, Replens,
      and condoms did not change the risk of BV in comparison to the provision of
      condoms alone.

PMID- 23133309
TI  - Distribution, Sources, and Association of Polycyclic Aromatic Hydrocarbons, Black
      Carbon, and Total Organic Carbon in Size-Segregated Soil Samples Along a
      Background-Urban-Rural Transect.
AB  - Soil samples were collected over a year-long period along a background-urban
      rural transect in Delhi, India for the analysis of polycyclic aromatic
      hydrocarbons (PAHs), black carbon (BC), and total organic carbon (TOC) in five
      grain size fractions, x, in MUm of 0<=x<53 (I), 53<=x<250 (II), 250<=x<500 (III),
      500<=x<2000 (IV), and their sum (total: T). Maximum concentrations of PAH, BC,
      and TOC were observed in the smallest fraction (I) comprising silt and clay,
      irrespective of site or season. Results of the molecular diagnostic ratios and
      principal component analysis (PCA) identified coal, wood, biomass burning, and
      vehicular emissions as major sources of PAHs at all the three sites, while BC/TOC
      ratios pointed toward biomass combustion as the chief source of carbonaceous
      species. This work presents the first such rural-urban transect study considering
      PAH, BC, and TOC in soil.

PMID- 23133310
TI  - Preparation of Modified Semi-Coke-Supported ZnFe(2)O(4) Sorbent with the
      Assistance of Ultrasonic Irradiation.
AB  - Modified semi-coke (MSC) supported ZnFe(2)O(4) was prepared under the condition
      of ultrasonic irradiation. Performance of the sorbents was tested using a fixed
      bed reactor as a hot gas desulfurizer. The MSC support, the mass ratio of zinc
      ferrites to the support, calcination temperature, and the ultrasonic conditions
      of power and time all had influences on the structure and the breakthrough
      behavior of the sorbent. Ultrasonic irradiation can help to make ZnFe(2)O(4)
      highly dispersed on MSC. ZnFe(2)O(4)/MSC had increased porosity and a larger
      specific surface area compared to unsupported ZnFe(2)O(4). The sorbent exhibited
      a higher sulfur capacity at the optimum preparing conditions, where the mass
      ratio of ZnFe(2)O(4) to MSC was 8:10, calcinated at 500 degrees C, and the
      ultrasonic power and time was 900 W and 1.5 h, respectively.

PMID- 23133311
TI  - Factors affecting poly(3-hydroxybutyrate) production from oil palm frond juice by
      Cupriavidus necator (CCUG52238(T)).
AB  - Factors influencing poly(3-hydroxybutyrate) P(3HB) production by Cupriavidus
      necator CCUG52238(T) utilizing oil palm frond (OPF) juice were clarified in this
      study. Effects of initial medium pH, agitation speed, and ammonium sulfate
      (NH(4))(2)SO(4) concentration on the production of P(3HB) were investigated in
      shake flasks experiments using OPF juice as the sole carbon source. The highest
      P(3HB) content was recorded at pH 7.0, agitation speed of 220 rpm, and
      (NH(4))(2)SO(4) concentration at 0.5 g/L. By culturing the wild-type strain of C.
      necator under the aforementioned conditions, the cell dry weight (CDW) and P(3HB)
      content obtained were 9.31 +/- 0.13 g/L and 45 +/- 1.5 wt.%, respectively. This
      accounted for 40% increment of P(3HB) content compared to the nonoptimized
      condition. In the meanwhile, the effect of dissolved oxygen tension (DOT) on
      P(3HB) production was investigated in a 2-L bioreactor. Highest CDW (11.37 g/L)
      and P(3HB) content (44 wt.%) were achieved when DOT level was set at 30%. P(3HB)
      produced from OPF juice had a tensile strength of 40 MPa and elongation at break
      of 8% demonstrated that P(3HB) produced from renewable and cheap carbon source is
      comparable to those produced from commercial substrate.

PMID- 23133312
TI  - Production of adenosine by ectonucleotidases: a key factor in tumor immunoescape.
AB  - It is now well known that tumor immunosurveillance contributes to the control of
      cancer growth. Many mechanisms can be used by cancer cells to avoid the antitumor
      immune response. One such mechanism relies on the capacity of cancer cells or
      more generally of the tumor microenvironment to generate adenosine, a major
      molecule involved in antitumor T cell response suppression. Adenosine is
      generated by the dephosphorylation of extracellular ATP released by dying tumor
      cells. The conversion of ATP into adenosine is mediated by ectonucleotidase
      molecules, namely, CD73 and CD39. These molecules are frequently expressed in the
      tumor bed by a wide range of cells including tumor cells, regulatory T cells,
      Th17 cells, myeloid cells, and stromal cells. Recent evidence suggests that
      targeting adenosine by inhibiting ectonucleotidases may restore the resident
      antitumor immune response or enhance the efficacy of antitumor therapies. This
      paper will underline the impact of adenosine and ectonucleotidases on the
      antitumor response.

PMID- 23133313
TI  - Drug Target Exploitable Structural Features of Adenylyl Cyclase Activity in
      Schistosoma mansoni.
AB  - The draft genome sequence of the parasitic flatworm Schistosoma mansoni (S.
      mansoni), a cause of schistosomiasis, encodes a predicted guanosine triphosphate
      (GTP) binding protein tagged Smp_059340.1. Smp_059340.1 is predicted to be a
      member of the G protein alpha-s subunit responsible for regulating adenylyl
      cyclase activity in S. mansoni and a possible drug target against the parasite.
      Our structural bioinformatics analyses identified key amino acid residues (Ser53,
      Thr188, Asp207 and Gly210) in the two molecular switches responsible for cycling
      the protein between active (GTP bound) and inactive (GDP bound) states. Residue
      Thr188 is located on Switch I region while Gly210 is located on Switch II region
      with Switch II longer than Switch I. The Asp207 is located on the G3 box motif
      and Ser53 is the binding residue for magnesium ion. These findings offer new
      insights into the dynamic and functional determinants of the Smp_059340.1 protein
      in regulating the S. mansoni life cycle. The binding interfaces and their
      residues could be used as starting points for selective modulations of
      interactions within the pathway using small molecules, peptides or mutagenesis.

PMID- 23133314
TI  - FOXO1 Up-Regulates Human L-selectin Expression Through Binding to a Consensus
      FOXO1 Motif.
AB  - L-selectin plays important roles in lymphocyte homing and leukocyte rolling.
      Mounting evidence shows that it is involved in many disease entities including
      diabetes, ischemia/reperfusion injuries, inflammatory diseases, and tumor
      metastasis. Regulation of L-selectin at protein level has been well
      characterized. However, the regulation of human L-selectin transcription remains
      largely unknown. To address transcriptional regulation of L-selectin, we cloned
      1088 bp 5' of the start codon ATG. Luciferase analysis of the serial 5' deletion
      mutants located the core promoter region at -288/-1. A major transcription
      initiation site was mapped at -115 by 5'RACE. Transcription factors Sp1, Ets1,
      Mzf1, Klf2, and Irf1 bind to and transactivate the L-selectin promoter.
      Significantly, FOXO1 binds to a FOXO1 motif, CCCTTTGG, at -87/-80, and
      transactivates the L-selectin promoter in a dose-dependent manner. Over
      expression of a constitutive-active FOXO1 increased the endogenous L-selectin
      expression in Jurkat cells. We conclude that FOXO1 regulates L-selectin
      expression through targeting its promoter.

PMID- 23133315
TI  - Taxanes for the treatment of metastatic breast cancer.
AB  - Taxanes have remained a cornerstone of breast cancer treatment over the past
      three decades, improving the lives of patients with both early- and late-stage
      disease. The purpose of this review is to summarize the current role of taxanes,
      including an albumin-bound formulation that enhances delivery of paclitaxel to
      tumors, in the management of metastatic breast cancer (MBC). Since the
      introduction of Cremophor EL-paclitaxel to the clinic in the mid-1990s, a
      substantial amount of investigation has gone into subjects such as formulation,
      dose, schedule, and taxane resistance, allowing physicians greater flexibility in
      treating patients with MBC. This review will also examine how the shrinking pool
      of taxane-naive patients, a result of the expansion of taxanes into the
      neoadjuvant and adjuvant settings, will respond to taxane retreatment for
      metastatic disease. Taxane treatment seems likely to continue to play an
      important role in the treatment of MBC.

PMID- 23133316
TI  - Atrial septal aneurysm mimicking a cor triatriatum sinister: a case report and
      review of the literature.
AB  - An atrial septal aneurysm (ASA) is a rare but well-recognized abnormality of
      uncertain clinical relevance. It is a localized bulging of the inter-atrial
      septum into either or both atria during the cardiac cycle. ASA has been reported
      as an unexpected finding during autopsy but may also be diagnosed in living
      patients by echocardiographic techniques.We present a 37-year-old woman with a
      recurrent atypical chest pain of one-year duration. She was found to have a
      congenital atrial septal aneurysm on evaluation. The echocardiographic images
      mimicked a left sided cor triatriatum sinister. She had no other symptoms and had
      no co-morbidities. There was no audible murmur.ASA can mimic cor-triatriatum and
      echocardiographic examination should be performed from multiple views before any
      echocardiographic diagnosis is made.

PMID- 23133317
TI  - Virilizing leydig-sertoli cell ovarian tumor associated with endometrioid
      carcinoma of the endometrium in a postmenopausal patient: case report and general
      considerations.
AB  - INTRODUCTION: Sertoli-Leydig cell tumors (SLCTs) are rare tumors mostly occurring
      in young women. Here we report an unusual case of a SLCT with simultaneous
      occurrence of endometrioid adenocarcinoma of the endometrium in a woman in
      menopause. CASE REPORT: A 67-year-old woman presented with progressive signs of
      virilization. Blood tests showed increased levels of testosterone, delta-4
      androstenedione, and dehydroepiandrosterone (DHEA). DHEA-sulphate, 17beta
      estradiol, estrone, and sex-hormone binding globulin serum levels were within the
      normal range. Magnetic resonance imaging revealed a solid mass of 2.7 * 2.9 cm in
      the right ovary set against the background of the uterus. The patient underwent
      bilateral salpingo-oophoretomy with hysterectomy. The mass in the right ovary was
      a differentiated SLCT. Incidentally, the endometrium revealed an endometrioid
      adenocacinoma. Following surgical treatment the plasma androgens dropped to
      normal levels, and signs and symptoms of virilization improved. CONCLUSION: SLCT
      should be suspected in postmenopausal women who present rapid progressive
      androgen excess symptoms with hyperandrogenemia.

PMID- 23133318
TI  - Vascular effects of bisphosphonates-a systematic review.
AB  - BACKGROUND: Osteoporosis and cardiovascular disease are interconnected entities
      with pathophysiological similarities. Bisphosphonates are therapeutic options
      available for resorptive bone diseases; however, experimental evidence has
      demonstrated a role for bisphosphonates in the inhibition of atherogenesis.
      METHODS: A systematic review of the vascular effects of bisphosphonates on
      atherosclerosis was performed. Vascular effects were evaluated by the thickening
      of the intima-media of carotid arteries and calcification of the coronary and
      aorta arteries. Electronic databases PubMed, The Cochrane Library, and Embase
      from January 1980 to May 2011 were searched. RESULTS: Of 169 potentially relevant
      articles, 9 clinical trials were selected. Two articles showed the benefit of the
      use of etidronate (-0.038 mm, P < 0.005) and alendronate (-0.025 mm, P < 0.05) on
      carotid artery intima-media thickening (CIMT) after one year. One article found
      no changes associated with the use of alendronate. The use of risedronate was
      associated with a reduction of plaque score on the carotid arteries (decrease of
      1% at 1 year, P = 0.015). Of those studies that evaluated the effect on coronary
      artery calcification (CAC), the results are conflicting: one study showed no
      changes with use of etidronate and in another, etidronate resulted in inhibition
      of the process of CAC after 1 year of follow-up (-372 mm(3) in CAC score, P <
      0.01). Three studies showed positive effects of etidronate on the aortic
      calcificaton (AC) score, showing no effect with use of ibandronate, and another
      showed a inhibition in the progression of the abdominal AC score with use of
      risendronate (P = 0.043). CONCLUSION: Bisphosphonates seem to have an inhibitory
      effect on the atherosclerotic process; however, larger placebo-controlled studies
      are needed to better clarify this issue.

PMID- 23133319
TI  - Efficacy and tolerability of pharmacotherapy options for the treatment of
      medullary thyroid cancer.
AB  - Metastatic and unresectable medullary thyroid carcinoma (MTC) is often difficult
      to treat as it is relatively unresponsive to radiation and conventional
      chemotherapy. This emphasizes the importance of the development of targeted
      therapies for advanced MTC. Vandetanib was approved by the US Food and Drug
      Administration for the treatment of symptomatic or progressive MTC in patients
      with advanced disease in April 2011. This therapy proved to be a breakthrough in
      the management of MTC. We review the efficacy and safety of this novel treatment
      and other treatments that are being evaluated in this disease.

PMID- 23133321
TI  - Improving instruction in medical libraries: the research agenda.

PMID- 23133322
TI  - Miss Manners for social networking: a new role for medical librarians.

PMID- 23133323
TI  - Teaching about teaching and instruction on instruction: a challenge for health
      sciences library education.
AB  - OBJECTIVE: This is a review of the master's-level curricula of the fifty-eight
      America Library Association-accredited library and information science programs
      and iSchools for evidence of coursework and content related to library
      instruction. Special emphasis is placed on the schools and programs that also
      offer coursework in medical or health sciences librarianship. METHODS: Fifty
      eight school and program websites were reviewed. Course titles and course
      descriptions for seventy-three separate classes were analyzed. Twenty-three
      syllabi were examined. RESULTS: All North American library education programs
      offer at least one course in the general area of library instruction; some
      programs offer multiple courses. No courses on instruction, however, are focused
      directly on the specialized area of health sciences librarianship. CONCLUSIONS:
      Master's degree students can take appropriate classes on library instruction, but
      the medical library profession needs to offer continuing education opportunities
      for practitioners who want to have specific instruction for the specialized world
      of the health sciences.

PMID- 23133324
TI  - Evidence-based medicine at the intersection of research interests between
      academic health sciences librarians and medical educators: a review of the
      literature.
AB  - OBJECTIVES: In 2008, the Association of Academic Health Sciences Libraries
      established an Education Research Task Force (ERTF) to plan research addressing
      research priorities outlined in key Association of American Medical Colleges
      reports. ERTF members conducted a literature review to describe the state of
      collaborative research at the intersection of medical education and health
      sciences librarianship. Analysis of initial results revealed instruction in
      evidence-based medicine (EBM) was a shared interest and is thus the focus of this
      review. METHODS: Searches on EBM teaching programs were conducted, and results
      were posted to a shared online citation management service. Individual articles
      were assessed and assigned metadata describing subject matter, scope, and format.
      RESULTS: Article analysis identified key themes. Most papers were descriptive
      narratives of curricular development. Evaluation studies were also prominent and
      often based on student satisfaction or self-reported competency. A smaller number
      of controlled studies provide evidence of impacts of librarian involvement in EBM
      instruction. CONCLUSIONS: Scholarship of EBM instruction is of common interest
      between medical educators and health sciences librarians. Coauthorship between
      the groups and distribution of literature points to a productive collaboration.
      An emerging literature of controlled studies measuring the impact of cross
      disciplinary efforts signals continued progress in the arena of EBM instruction.

PMID- 23133325
TI  - Best methods for evaluating educational impact: a comparison of the efficacy of
      commonly used measures of library instruction.
AB  - OBJECTIVES AND BACKGROUND: Libraries are increasingly called upon to demonstrate
      student learning outcomes and the tangible benefits of library educational
      programs. This study reviewed and compared the efficacy of traditionally used
      measures for assessing library instruction, examining the benefits and drawbacks
      of assessment measures and exploring the extent to which knowledge, attitudes,
      and behaviors actually paralleled demonstrated skill levels. METHODS: An overview
      of recent literature on the evaluation of information literacy education
      addressed these questions: (1) What evaluation measures are commonly used for
      evaluating library instruction? (2) What are the pros and cons of popular
      evaluation measures? (3) What are the relationships between measures of skills
      versus measures of attitudes and behavior? Research outcomes were used to
      identify relationships between measures of attitudes, behaviors, and skills,
      which are typically gathered via attitudinal surveys, written skills tests, or
      graded exercises. RESULTS AND CONCLUSIONS: Results provide useful information
      about the efficacy of instructional evaluation methods, including showing
      significant disparities between attitudes, skills, and information usage
      behaviors. This information can be used by librarians to implement the most
      appropriate evaluation methods for measuring important variables that accurately
      demonstrate students' attitudes, behaviors, or skills.

PMID- 23133326
TI  - Is literature search training for medical students and residents effective? a
      literature review.
AB  - OBJECTIVES: This literature review examines the effectiveness of literature
      searching skills instruction for medical students or residents, as determined in
      studies that either measure learning before and after an intervention or compare
      test and control groups. The review reports on the instruments used to measure
      learning and on their reliability and validity, where available. Finally, a
      summary of learning outcomes is presented. METHODS: Fifteen studies published
      between 1998 and 2011 were identified for inclusion in the review. The selected
      studies all include a description of the intervention, a summary of the test used
      to measure learning, and the results of the measurement. RESULTS: Instruction
      generally resulted in improvement in clinical question writing, search strategy
      construction, article selection, and resource usage. CONCLUSION: Although the
      findings of most of the studies indicate that the current instructional methods
      are effective, the study designs are generally weak, there is little evidence
      that learning persists over time, and few validated methods of skill measurement
      have been developed.

PMID- 23133327
TI  - Developing health information literacy: a needs analysis from the perspective of
      preprofessional health students.
AB  - OBJECTIVE: The research identified the skills, if any, that health
      preprofessional students wished to develop after receiving feedback on skill gaps
      as well as any strategies they intended to use to address these gaps. METHODS: A
      qualitative approach was used to elicit students' reflections on building health
      information literacy skills. First, the students took the Research Readiness Self
      Assessment instrument, which measured their health information literacy, and then
      they received individually tailored feedback about their scores and skill gaps.
      Second, students completed a post-assessment survey asking how they intended to
      close identified gaps in their skills on these. Three trained coders analyzed
      qualitative comments by 181 students and grouped them into themes relating to
      "what skills to improve" and "how to improve them." RESULTS: Students intended to
      develop library skills (64% of respondents), Internet skills (63%), and
      information evaluation skills (63%). Most students reported that they would use
      library staff members' assistance (55%), but even more respondents (82%) planned
      to learn the skills by practicing on their own. Getting help from librarians was
      a much more popular learning strategy than getting assistance from peers (20%) or
      professors (17%). CONCLUSIONS: The study highlighted the importance of providing
      health preprofessional students with resources to improve skills on their own,
      remote access to library staff members, and instruction on the complexity of
      building health literacy skills, while also building relationships among
      students, librarians, and faculty.

PMID- 23133328
TI  - Aligning library instruction with the needs of basic sciences graduate students:
      a case study.
AB  - QUESTION: How can an existing library instruction program be reconfigured to
      reach basic sciences graduate students and other patrons missed by curriculum
      based instruction? SETTING: The setting is an academic health sciences library
      that serves both the university and its affiliated teaching hospital. METHODS:
      The existing program was redesigned to incorporate a series of seven workshops
      that encompassed the range of information literacy skills that graduate students
      in the basic sciences need. In developing the new model, the teaching librarians
      made changes in pedagogy, technology, marketing, and assessment strategies.
      RESULTS: Total attendance at the sessions increased substantially in the first 2
      years of the new model, increasing from an average of 20 per semester to an
      average of 124. Survey results provided insight about what patrons wanted to
      learn and how best to teach it. CONCLUSION: Modifying the program's content and
      structure resulted in a program that appealed to the target audience.

PMID- 23133329
TI  - Time to rethink the role of the library in educating doctors: driving information
      literacy in the clinical environment.
AB  - QUESTION: Can information literacy (IL) be embedded into the curriculum and
      clinical environment to facilitate patient care and lifelong learning? SETTING:
      The Australian School of Advanced Medicine (ASAM) provides competence-based
      programs incorporating patient-centred care and lifelong learning. ASAM
      librarians use outcomes-based educational theory to embed and assess IL into
      ASAM's educational and clinical environments. METHODS: A competence-based IL
      program was developed where learning outcomes were linked to current patients and
      assessed with checklists. Weekly case presentations included clinicians'
      literature search strategies, results, and conclusions. Librarians provided
      support to clinicians' literature searches and assessed their presentations using
      a checklist. MAIN RESULTS: Outcome data showed clinicians' searching skills
      improved over time; however, advanced MEDLINE searching remained challenging for
      some. Recommendations are provided. CONCLUSION: IL learning that takes place in
      context using measurable outcomes is more meaningful, is enduring, and likely
      contributes to patient care. Competence-based assessment drives learning in this
      environment.

PMID- 23133330
TI  - "Information Survival Skills": a medical school elective.
AB  - OBJECTIVE: The authors developed an elective course to assist students in (1)
      understanding the changing nature of scholarly communication and online
      publishing, (2) identifying resources and strategies for searching current best
      evidence, and (3) demonstrating effective communication of information. SETTING:
      The course took place in a medical school in the Southwest. PARTICIPANTS: Second-
      and third-year medical students participated in the course. INTERVENTION: A pass
      fail, undergraduate-level elective was first offered October to December 2006.
      This 7.5 hour course, developed and co-taught by 2 health sciences library
      faculty, consisted of hands-on exercises, small group discussion, and didactic
      lecture. CONCLUSION: Presenting a medical school elective is one possible outlet
      for intensive bibliographic instruction. Illustrating the flow of information
      from creation to management and presentation affords students an opportunity to
      understand information in context. This elective has been consistently ranked
      very high in student evaluations and led to new and expanded teaching
      opportunities.

PMID- 23133331
TI  - "Genomics and Translational Medicine for Information Professionals": an
      innovative course to educate the next generation of librarians.

PMID- 23133332
TI  - Innovation in evidence-based medicine education and assessment: an interactive
      class for third- and fourth-year medical students.

PMID- 23133333
TI  - Development of a post-master's online certificate in health sciences
      librarianship.

PMID- 23133334
TI  - Broadening instructional scope with network visualization.

PMID- 23133335
TI  - The use of anonymous pop-quizzes (APQs) as a tool to reinforce learning.

PMID- 23133336
TI  - Use of instructional design theory and an individualized hybrid strategy for
      assessment in library-based instruction.

PMID- 23133339
TI  - Transcranial direct current stimulation in tinnitus patients: a systemic review
      and meta-analysis.
AB  - Although transcranial direct current stimulation (tDCS) has already been used to
      manage tinnitus patients, paucity of reports and variations in protocols preclude
      a comprehensive understanding. Hence, we conducted a meta-analysis based on
      systemic review to assess effectiveness of tDCS in tinnitus management and to
      compare stimulation parameters. PubMed was searched for tDCS studies in tinnitus.
      For randomized controlled trials (RCTs), a meta-analysis was performed. A total
      of 17 studies were identified and 6 of them were included in the systemic review
      and 2 RCTs were included in the meta-analysis. Overall 39.5% responded to active
      tDCS with a mean tinnitus intensity reduction of 13.5%. Additionally, left
      temporal area (LTA) and bifrontal tDCS indicated comparable results. Active tDCS
      was found to be more effective than sham tDCS for tinnitus intensity reduction
      (Hedges' g = .77, 95% confidence interval 0.23-1.31). The efficacy of tDCS in
      tinnitus could not be fully confirmed by the current study because of the limited
      number of studies, but all studies included in the current systemic review and
      meta-analysis demonstrated significant tinnitus intensity improvement. Therefore,
      tDCS may be a promising tool for tinnitus management. Future RCTs in a large
      series regarding the efficacy as well as the comparison between LTA- and
      bifrontal tDCS are recommended.

PMID- 23133340
TI  - Bringing clarity to the reporting of health equity.
AB  - The PLOS Medicine editors discuss the new extension to the PRISMA reporting
      guidelines, PRISMA for Equity (PRISMA-E), and why it is relevant to the journal
      and to health research more generally.

PMID- 23133341
TI  - Incorporating Phase-Dependent Polarizability in Non-Additive Electrostatic Models
      for Molecular Dynamics Simulations of the Aqueous Liquid-Vapor Interface.
AB  - We discuss a new classical water force field that explicitly accounts for
      differences in polarizability between liquid and vapor phases. The TIP4P-QDP (4
      point transferable intermolecular potential with charge dependent-polarizability)
      force field is a modification of the original TIP4P-FQ fluctuating charge water
      force field of Rick et al.(1) that self-consistently adjusts its atomic hardness
      parameters via a scaling function dependent on the M-site charge. The
      electronegativity (chi) parameters are also scaled in order to reproduce
      condensed-phase dipole moments of comparable magnitude to TIP4P-FQ. TIP4P-QDP is
      parameterized to reproduce experimental gas-phase and select condensed-phase
      properties. The TIP4P-QDP water model possesses a gas phase polarizability of
      1.40 A(3) and gas-phase dipole moment of 1.85 Debye, in excellent agreement with
      experiment and high-level ab initio predictions. The liquid density of TIP4P-QDP
      is 0.9954(+/-0.0002) g/cm(3) at 298 K and 1 atmosphere, and the enthalpy of
      vaporization is 10.55(+/-0.12) kcal/mol. Other condensed-phase properties such as
      the isobaric heat capacity, isothermal compressibility, and diffusion constant
      are also calculated within reasonable accuracy of experiment and consistent with
      predictions of other current state-of-the-art water force fields. The average
      molecular dipole moment of TIP4P-QDP in the condensed phase is 2.641(+/-0.001)
      Debye, approximately 0.02 Debye higher than TIP4P-FQ and within the range of
      values currently surmised for the bulk liquid. The dielectric constant, epsilon =
      85.8 +/- 1.0, is 10% higher than experiment. This is reasoned to be due to the
      increase in the condensed phase dipole moment over TIP4P-FQ, which estimates
      epsilon remarkably well. Radial distribution functions for TIP4P-QDP and TIP4P-FQ
      show similar features, with TIP4P-QDP showing slightly reduced peak heights and
      subtle shifts towards larger distance interactions. Since the greatest effects of
      the phase-dependent polarizability are anticipated in regions with both liquid
      and vapor character, interfacial simulations of TIP4P-QDP were performed and
      compared to TIP4P-FQ, a static polarizability analog. Despite similar features in
      density profiles such as the position of the GDS and interfacial width, enhanced
      dipole moments are observed for the TIP4P-QDP interface and onset of the vapor
      phase. Water orientational profiles show an increased preference (over TIP4P-FQ)
      in the orientation of the permanent dipole vector of the molecule within the
      interface; an enhanced z-induced dipole moment directly results from this
      preference. Hydrogen bond formation is lower, on average, in the bulk for TIP4P
      QDP than TIP4P-FQ. However, the average number of hydrogen bonds formed by TIP4P
      QDP in the interface exceeds that of TIP4P-FQ, and observed hydrogen bond
      networks extend further into the gaseous region. The TIP4P-QDP interfacial
      potential, calculated to be -11.98(+/-0.08) kcal/mol, is less favorable than that
      for TIP4P-FQ by approximately 2% as a result of a diminished quadrupole
      contribution. Surface tension is calculated within a 1.3% reduction from the
      experimental value. Results reported demonstrate TIP4P-QDP as a model comparable
      to the popular TIP4P-FQ while accounting for a physical effect previously
      neglected by other water models. Further refinements to this model, as well as
      future applications are discussed.

PMID- 23133342
TI  - Predictive dynamics of human pain perception.
AB  - While the static magnitude of thermal pain perception has been shown to follow a
      power-law function of the temperature, its dynamical features have been largely
      overlooked. Due to the slow temporal experience of pain, multiple studies now
      show that the time evolution of its magnitude can be captured with continuous
      online ratings. Here we use such ratings to model quantitatively the temporal
      dynamics of thermal pain perception. We show that a differential equation
      captures the details of the temporal evolution in pain ratings in individual
      subjects for different stimulus pattern complexities, and also demonstrates
      strong predictive power to infer pain ratings, including readouts based only on
      brain functional images.

PMID- 23133343
TI  - How recent history affects perception: the normative approach and its heuristic
      approximation.
AB  - There is accumulating evidence that prior knowledge about expectations plays an
      important role in perception. The Bayesian framework is the standard
      computational approach to explain how prior knowledge about the distribution of
      expected stimuli is incorporated with noisy observations in order to improve
      performance. However, it is unclear what information about the prior distribution
      is acquired by the perceptual system over short periods of time and how this
      information is utilized in the process of perceptual decision making. Here we
      address this question using a simple two-tone discrimination task. We find that
      the "contraction bias", in which small magnitudes are overestimated and large
      magnitudes are underestimated, dominates the pattern of responses of human
      participants. This contraction bias is consistent with the Bayesian hypothesis in
      which the true prior information is available to the decision-maker. However, a
      trial-by-trial analysis of the pattern of responses reveals that the contribution
      of most recent trials to performance is overweighted compared with the
      predictions of a standard Bayesian model. Moreover, we study participants'
      performance in a-typical distributions of stimuli and demonstrate substantial
      deviations from the ideal Bayesian detector, suggesting that the brain utilizes a
      heuristic approximation of the Bayesian inference. We propose a biologically
      plausible model, in which decision in the two-tone discrimination task is based
      on a comparison between the second tone and an exponentially-decaying average of
      the first tone and past tones. We show that this model accounts for both the
      contraction bias and the deviations from the ideal Bayesian detector hypothesis.
      These findings demonstrate the power of Bayesian-like heuristics in the brain, as
      well as their limitations in their failure to fully adapt to novel environments.

PMID- 23133344
TI  - The effect of bacterial recombination on adaptation on fitness landscapes with
      limited peak accessibility.
AB  - There is ample empirical evidence revealing that fitness landscapes are often
      complex: the fitness effect of a newly arisen mutation can depend strongly on the
      allelic state at other loci. However, little is known about the effects of
      recombination on adaptation on such fitness landscapes. Here, we investigate how
      recombination influences the rate of adaptation on a special type of complex
      fitness landscapes. On these landscapes, the mutational trajectories from the
      least to the most fit genotype are interrupted by genotypes with low relative
      fitness. We study the dynamics of adapting populations on landscapes with
      different compositions and numbers of low fitness genotypes, with and without
      recombination. Our results of the deterministic model (assuming an infinite
      population size) show that recombination generally decelerates adaptation on
      these landscapes. However, in finite populations, this deceleration is outweighed
      by the accelerating Fisher-Muller effect under certain conditions. We conclude
      that recombination has complex effects on adaptation that are highly dependent on
      the particular fitness landscape, population size and recombination rate.

PMID- 23133345
TI  - Next-generation sequencing of human mitochondrial reference genomes uncovers high
      heteroplasmy frequency.
AB  - We describe methods for rapid sequencing of the entire human mitochondrial genome
      (mtgenome), which involve long-range PCR for specific amplification of the
      mtgenome, pyrosequencing, quantitative mapping of sequence reads to identify
      sequence variants and heteroplasmy, as well as de novo sequence assembly. These
      methods have been used to study 40 publicly available HapMap samples of European
      (CEU) and African (YRI) ancestry to demonstrate a sequencing error rate <5.63*10(
      4), nucleotide diversity of 1.6*10(-3) for CEU and 3.7*10(-3) for YRI, patterns
      of sequence variation consistent with earlier studies, but a higher rate of
      heteroplasmy varying between 10% and 50%. These results demonstrate that next
      generation sequencing technologies allow interrogation of the mitochondrial
      genome in greater depth than previously possible which may be of value in biology
      and medicine.

PMID- 23133346
TI  - The role of social contacts and original antigenic sin in shaping the age pattern
      of immunity to seasonal influenza.
AB  - Recent serological studies of seasonal influenza A in humans suggest a striking
      characteristic profile of immunity against age, which holds across different
      countries and against different subtypes of influenza. For both H1N1 and H3N2,
      the proportion of the population seropositive to recently circulated strains
      peaks in school-age children, reaches a minimum between ages 35-65, then rises
      again in the older ages. This pattern is little understood. Variable mixing
      between different age classes can have a profound effect on disease dynamics, and
      is hence the obvious candidate explanation for the profile, but using a
      mathematical model of multiple influenza strains, we see that age dependent
      transmission based on mixing data from social contact surveys cannot on its own
      explain the observed pattern. Instead, the number of seropositive individuals in
      a population may be a consequence of 'original antigenic sin'; if the first
      infection of a lifetime dominates subsequent immune responses, we demonstrate
      that it is possible to reproduce the observed relationship between age and
      seroprevalence. We propose a candidate mechanism for this relationship, by which
      original antigenic sin, along with antigenic drift and vaccination, results in
      the age profile of immunity seen in empirical studies.

PMID- 23133347
TI  - Modeling protective anti-tumor immunity via preventative cancer vaccines using a
      hybrid agent-based and delay differential equation approach.
AB  - A next generation approach to cancer envisions developing preventative
      vaccinations to stimulate a person's immune cells, particularly cytotoxic T
      lymphocytes (CTLs), to eliminate incipient tumors before clinical detection. The
      purpose of our study is to quantitatively assess whether such an approach would
      be feasible, and if so, how many anti-cancer CTLs would have to be primed against
      tumor antigen to provide significant protection. To understand the relevant
      dynamics, we develop a two-compartment model of tumor-immune interactions at the
      tumor site and the draining lymph node. We model interactions at the tumor site
      using an agent-based model (ABM) and dynamics in the lymph node using a system of
      delay differential equations (DDEs). We combine the models into a hybrid ABM-DDE
      system and investigate dynamics over a wide range of parameters, including cell
      proliferation rates, tumor antigenicity, CTL recruitment times, and initial
      memory CTL populations. Our results indicate that an anti-cancer memory CTL pool
      of 3% or less can successfully eradicate a tumor population over a wide range of
      model parameters, implying that a vaccination approach is feasible. In addition,
      sensitivity analysis of our model reveals conditions that will result in rapid
      tumor destruction, oscillation, and polynomial rather than exponential decline in
      the tumor population due to tumor geometry.

PMID- 23133348
TI  - Incorporating 16S gene copy number information improves estimates of microbial
      diversity and abundance.
AB  - The abundance of different SSU rRNA ("16S") gene sequences in environmental
      samples is widely used in studies of microbial ecology as a measure of microbial
      community structure and diversity. However, the genomic copy number of the 16S
      gene varies greatly - from one in many species to up to 15 in some bacteria and
      to hundreds in some microbial eukaryotes. As a result of this variation the
      relative abundance of 16S genes in environmental samples can be attributed both
      to variation in the relative abundance of different organisms, and to variation
      in genomic 16S copy number among those organisms. Despite this fact, many studies
      assume that the abundance of 16S gene sequences is a surrogate measure of the
      relative abundance of the organisms containing those sequences. Here we present a
      method that uses data on sequences and genomic copy number of 16S genes along
      with phylogenetic placement and ancestral state estimation to estimate organismal
      abundances from environmental DNA sequence data. We use theory and simulations to
      demonstrate that 16S genomic copy number can be accurately estimated from the
      short reads typically obtained from high-throughput environmental sequencing of
      the 16S gene, and that organismal abundances in microbial communities are more
      strongly correlated with estimated abundances obtained from our method than with
      gene abundances. We re-analyze several published empirical data sets and
      demonstrate that the use of gene abundance versus estimated organismal abundance
      can lead to different inferences about community diversity and structure and the
      identity of the dominant taxa in microbial communities. Our approach will allow
      microbial ecologists to make more accurate inferences about microbial diversity
      and abundance based on 16S sequence data.

PMID- 23133349
TI  - Evolutionary analysis of human immunodeficiency virus type 1 therapies based on
      conditionally replicating vectors.
AB  - Efforts to reduce the viral load of human immunodeficiency virus type 1 (HIV-1)
      during long-term treatment are challenged by the evolution of anti-viral
      resistance mutants. Recent studies have shown that gene therapy approaches based
      on conditionally replicating vectors (CRVs) could have many advantages over anti
      viral drugs and other approaches to therapy, potentially including the ability to
      circumvent the problem of evolved resistance. However, research to date has not
      explored the evolutionary consequences of long-term treatment of HIV-1 infections
      with conditionally replicating vectors. In this study, we analyze a computational
      model of the within-host co-evolutionary dynamics of HIV-1 and conditionally
      replicating vectors, using the recently proposed 'therapeutic interfering
      particle' as an example. The model keeps track of the stochastic process of viral
      mutation, and the deterministic population dynamics of T cells as well as
      different strains of CRV and HIV-1 particles. We show that early in the co
      infection, mutant HIV-1 genotypes that escape suppression by CRV therapy appear;
      this is similar to the dynamics observed in drug treatments and other gene
      therapies. In contrast to other treatments, however, the CRV population is able
      to evolve and catch up with the dominant HIV-1 escape mutant and persist long
      term in most cases. On evolutionary grounds, gene therapies based on CRVs appear
      to be a promising tool for long-term treatment of HIV-1. Our model allows us to
      propose design principles to optimize the efficacy of this class of gene
      therapies. In addition, because of the analogy between CRVs and naturally
      occurring defective interfering particles, our results also shed light on the co
      evolutionary dynamics of wild-type viruses and their defective interfering
      particles during natural infections.

PMID- 23133350
TI  - Emergence of the mitochondrial reticulum from fission and fusion dynamics.
AB  - Mitochondria form a dynamic tubular reticulum within eukaryotic cells. Currently,
      quantitative understanding of its morphological characteristics is largely
      absent, despite major progress in deciphering the molecular fission and fusion
      machineries shaping its structure. Here we address the principles of formation
      and the large-scale organization of the cell-wide network of mitochondria. On the
      basis of experimentally determined structural features we establish the tip-to
      tip and tip-to-side fission and fusion events as dominant reactions in the
      motility of this organelle. Subsequently, we introduce a graph-based model of the
      chondriome able to encompass its inherent variability in a single framework.
      Using both mean-field deterministic and explicit stochastic mathematical methods
      we establish a relationship between the chondriome structural network
      characteristics and underlying kinetic rate parameters. The computational
      analysis indicates that mitochondrial networks exhibit a percolation threshold.
      Intrinsic morphological instability of the mitochondrial reticulum resulting from
      its vicinity to the percolation transition is proposed as a novel mechanism that
      can be utilized by cells for optimizing their functional competence via dynamic
      remodeling of the chondriome. The detailed size distribution of the network
      components predicted by the dynamic graph representation introduces a
      relationship between chondriome characteristics and cell function. It forms a
      basis for understanding the architecture of mitochondria as a cell-wide but
      inhomogeneous organelle. Analysis of the reticulum adaptive configuration offers
      a direct clarification for its impact on numerous physiological processes
      strongly dependent on mitochondrial dynamics and organization, such as efficiency
      of cellular metabolism, tissue differentiation and aging.

PMID- 23133352
TI  - Disease prevention versus data privacy: using landcover maps to inform spatial
      epidemic models.
AB  - The availability of epidemiological data in the early stages of an outbreak of an
      infectious disease is vital for modelers to make accurate predictions regarding
      the likely spread of disease and preferred intervention strategies. However, in
      some countries, the necessary demographic data are only available at an aggregate
      scale. We investigated the ability of models of livestock infectious diseases to
      predict epidemic spread and obtain optimal control policies in the event of
      imperfect, aggregated data. Taking a geographic information approach, we used
      land cover data to predict UK farm locations and investigated the influence of
      using these synthetic location data sets upon epidemiological predictions in the
      event of an outbreak of foot-and-mouth disease. When broadly classified land
      cover data were used to create synthetic farm locations, model predictions
      deviated significantly from those simulated on true data. However, when more
      resolved subclass land use data were used, moderate to highly accurate
      predictions of epidemic size, duration and optimal vaccination and ring culling
      strategies were obtained. This suggests that a geographic information approach
      may be useful where individual farm-level data are not available, to allow
      predictive analyses to be carried out regarding the likely spread of disease.
      This method can also be used for contingency planning in collaboration with
      policy makers to determine preferred control strategies in the event of a future
      outbreak of infectious disease in livestock.

PMID- 23133351
TI  - Integrating cellular metabolism into a multiscale whole-body model.
AB  - Cellular metabolism continuously processes an enormous range of external
      compounds into endogenous metabolites and is as such a key element in human
      physiology. The multifaceted physiological role of the metabolic network
      fulfilling the catalytic conversions can only be fully understood from a whole
      body perspective where the causal interplay of the metabolic states of individual
      cells, the surrounding tissue and the whole organism are simultaneously
      considered. We here present an approach relying on dynamic flux balance analysis
      that allows the integration of metabolic networks at the cellular scale into
      standardized physiologically-based pharmacokinetic models at the whole-body
      level. To evaluate our approach we integrated a genome-scale network
      reconstruction of a human hepatocyte into the liver tissue of a physiologically
      based pharmacokinetic model of a human adult. The resulting multiscale model was
      used to investigate hyperuricemia therapy, ammonia detoxification and paracetamol
      induced toxication at a systems level. The specific models simultaneously
      integrate multiple layers of biological organization and offer mechanistic
      insights into pathology and medication. The approach presented may in future
      support a mechanistic understanding in diagnostics and drug development.

PMID- 23133353
TI  - Evolution of associative learning in chemical networks.
AB  - Organisms that can learn about their environment and modify their behaviour
      appropriately during their lifetime are more likely to survive and reproduce than
      organisms that do not. While associative learning - the ability to detect
      correlated features of the environment - has been studied extensively in nervous
      systems, where the underlying mechanisms are reasonably well understood,
      mechanisms within single cells that could allow associative learning have
      received little attention. Here, using in silico evolution of chemical networks,
      we show that there exists a diversity of remarkably simple and plausible chemical
      solutions to the associative learning problem, the simplest of which uses only
      one core chemical reaction. We then asked to what extent a linear combination of
      chemical concentrations in the network could approximate the ideal Bayesian
      posterior of an environment given the stimulus history so far? This Bayesian
      analysis revealed the 'memory traces' of the chemical network. The implication of
      this paper is that there is little reason to believe that a lack of suitable
      phenotypic variation would prevent associative learning from evolving in cell
      signalling, metabolic, gene regulatory, or a mixture of these networks in cells.

PMID- 23133354
TI  - Theory on the coupled stochastic dynamics of transcription and splice-site
      recognition.
AB  - Eukaryotic genes are typically split into exons that need to be spliced together
      to form the mature mRNA. The splicing process depends on the dynamics and
      interactions among transcription by the RNA polymerase II complex (RNAPII) and
      the spliceosomal complex consisting of multiple small nuclear ribonucleo proteins
      (snRNPs). Here we propose a biophysically plausible initial theory of splicing
      that aims to explain the effects of the stochastic dynamics of snRNPs on the
      splicing patterns of eukaryotic genes. We consider two different ways to model
      the dynamics of snRNPs: pure three-dimensional diffusion and a combination of
      three- and one-dimensional diffusion along the emerging pre-mRNA. Our theoretical
      analysis shows that there exists an optimum position of the splice sites on the
      growing pre-mRNA at which the time required for snRNPs to find the 5' donor site
      is minimized. The minimization of the overall search time is achieved mainly via
      the increase in non-specific interactions between the snRNPs and the growing pre
      mRNA. The theory further predicts that there exists an optimum transcript length
      that maximizes the probabilities for exons to interact with the snRNPs. We
      evaluate these theoretical predictions by considering human and mouse exon
      microarray data as well as RNAseq data from multiple different tissues. We
      observe that there is a broad optimum position of splice sites on the growing pre
      mRNA and an optimum transcript length, which are roughly consistent with the
      theoretical predictions. The theoretical and experimental analyses suggest that
      there is a strong interaction between the dynamics of RNAPII and the stochastic
      nature of snRNP search for 5' donor splicing sites.

PMID- 23133355
TI  - A characterization of scale invariant responses in enzymatic networks.
AB  - An ubiquitous property of biological sensory systems is adaptation: a step
      increase in stimulus triggers an initial change in a biochemical or physiological
      response, followed by a more gradual relaxation toward a basal, pre-stimulus
      level. Adaptation helps maintain essential variables within acceptable bounds and
      allows organisms to readjust themselves to an optimum and non-saturating
      sensitivity range when faced with a prolonged change in their environment.
      Recently, it was shown theoretically and experimentally that many adapting
      systems, both at the organism and single-cell level, enjoy a remarkable
      additional feature: scale invariance, meaning that the initial, transient
      behavior remains (approximately) the same even when the background signal level
      is scaled. In this work, we set out to investigate under what conditions a
      broadly used model of biochemical enzymatic networks will exhibit scale-invariant
      behavior. An exhaustive computational study led us to discover a new property of
      surprising simplicity and generality, uniform linearizations with fast output
      (ULFO), whose validity we show is both necessary and sufficient for scale
      invariance of three-node enzymatic networks (and sufficient for any number of
      nodes). Based on this study, we go on to develop a mathematical explanation of
      how ULFO results in scale invariance. Our work provides a surprisingly
      consistent, simple, and general framework for understanding this phenomenon, and
      results in concrete experimental predictions.

PMID- 23133356
TI  - The role of flexibility and conformational selection in the binding promiscuity
      of PDZ domains.
AB  - In molecular recognition, it is often the case that ligand binding is coupled to
      conformational change in one or both of the binding partners. Two hypotheses
      describe the limiting cases involved; the first is the induced fit and the second
      is the conformational selection model. The conformational selection model
      requires that the protein adopts conformations that are similar to the ligand
      bound conformation in the absence of ligand, whilst the induced-fit model
      predicts that the ligand-bound conformation of the protein is only accessible
      when the ligand is actually bound. The flexibility of the apo protein clearly
      plays a major role in these interpretations. For many proteins involved in
      signaling pathways there is the added complication that they are often
      promiscuous in that they are capable of binding to different ligand partners. The
      relationship between protein flexibility and promiscuity is an area of active
      research and is perhaps best exemplified by the PDZ domain family of proteins. In
      this study we use molecular dynamics simulations to examine the relationship
      between flexibility and promiscuity in five PDZ domains: the human Dvl2
      (Dishevelled-2) PDZ domain, the human Erbin PDZ domain, the PDZ1 domain of InaD
      (inactivation no after-potential D protein) from fruit fly, the PDZ7 domain of
      GRIP1 (glutamate receptor interacting protein 1) from rat and the PDZ2 domain of
      PTP-BL (protein tyrosine phosphatase) from mouse. We show that despite their high
      structural similarity, the PDZ binding sites have significantly different
      dynamics. Importantly, the degree of binding pocket flexibility was found to be
      closely related to the various characteristics of peptide binding specificity and
      promiscuity of the five PDZ domains. Our findings suggest that the intrinsic
      motions of the apo structures play a key role in distinguishing functional
      properties of different PDZ domains and allow us to make predictions that can be
      experimentally tested.

PMID- 23133357
TI  - Comparative analysis of RNA families reveals distinct repertoires for each domain
      of life.
AB  - The RNA world hypothesis, that RNA genomes and catalysts preceded DNA genomes and
      genetically-encoded protein catalysts, has been central to models for the early
      evolution of life on Earth. A key part of such models is continuity between the
      earliest stages in the evolution of life and the RNA repertoires of extant
      lineages. Some assessments seem consistent with a diverse RNA world, yet direct
      continuity between modern RNAs and an RNA world has not been demonstrated for the
      majority of RNA families, and, anecdotally, many RNA functions appear restricted
      in their distribution. Despite much discussion of the possible antiquity of RNA
      families, no systematic analyses of RNA family distribution have been performed.
      To chart the broad evolutionary history of known RNA families, we performed
      comparative genomic analysis of over 3 million RNA annotations spanning 1446
      families from the Rfam 10 database. We report that 99% of known RNA families are
      restricted to a single domain of life, revealing discrete repertoires for each
      domain. For the 1% of RNA families/clans present in more than one domain, over
      half show evidence of horizontal gene transfer (HGT), and the rest show a
      vertical trace, indicating the presence of a complex protein synthesis machinery
      in the Last Universal Common Ancestor (LUCA) and consistent with the evolutionary
      history of the most ancient protein-coding genes. However, with limited
      interdomain transfer and few RNA families exhibiting demonstrable antiquity as
      predicted under RNA world continuity, our results indicate that the majority of
      modern cellular RNA repertoires have primarily evolved in a domain-specific
      manner.

PMID- 23133358
TI  - Reconstructing the dynamics of HIV evolution within hosts from serial deep
      sequence data.
AB  - At the early stage of infection, human immunodeficiency virus (HIV)-1
      predominantly uses the CCR5 coreceptor for host cell entry. The subsequent
      emergence of HIV variants that use the CXCR4 coreceptor in roughly half of all
      infections is associated with an accelerated decline of CD4+ T-cells and rate of
      progression to AIDS. The presence of a 'fitness valley' separating CCR5- and
      CXCR4-using genotypes is postulated to be a biological determinant of whether the
      HIV coreceptor switch occurs. Using phylogenetic methods to reconstruct the
      evolutionary dynamics of HIV within hosts enables us to discriminate between
      competing models of this process. We have developed a phylogenetic pipeline for
      the molecular clock analysis, ancestral reconstruction, and visualization of deep
      sequence data. These data were generated by next-generation sequencing of HIV RNA
      extracted from longitudinal serum samples (median 7 time points) from 8 untreated
      subjects with chronic HIV infections (Amsterdam Cohort Studies on HIV-1 infection
      and AIDS). We used the known dates of sampling to directly estimate rates of
      evolution and to map ancestral mutations to a reconstructed timeline in units of
      days. HIV coreceptor usage was predicted from reconstructed ancestral sequences
      using the geno2pheno algorithm. We determined that the first mutations
      contributing to CXCR4 use emerged about 16 (per subject range 4 to 30) months
      before the earliest predicted CXCR4-using ancestor, which preceded the first
      positive cell-based assay of CXCR4 usage by 10 (range 5 to 25) months. CXCR4
      usage arose in multiple lineages within 5 of 8 subjects, and ancestral lineages
      following alternate mutational pathways before going extinct were common. We
      observed highly patient-specific distributions and time-scales of mutation
      accumulation, implying that the role of a fitness valley is contingent on the
      genotype of the transmitted variant.

PMID- 23133359
TI  - Dynamic control of selectivity in the ubiquitination pathway revealed by an ASP
      to GLU substitution in an intra-molecular salt-bridge network.
AB  - Ubiquitination relies on a subtle balance between selectivity and promiscuity
      achieved through specific interactions between ubiquitin-conjugating enzymes
      (E2s) and ubiquitin ligases (E3s). Here, we report how a single aspartic to
      glutamic acid substitution acts as a dynamic switch to tip the selectivity
      balance of human E2s for interaction toward E3 RING-finger domains. By combining
      molecular dynamic simulations, experimental yeast-two-hybrid screen of E2-E3
      (RING) interactions and mutagenesis, we reveal how the dynamics of an internal
      salt-bridge network at the rim of the E2-E3 interaction surface controls the
      balance between an "open", binding competent, and a "closed", binding incompetent
      state. The molecular dynamic simulations shed light on the fine mechanism of this
      molecular switch and allowed us to identify its components, namely an
      aspartate/glutamate pair, a lysine acting as the central switch and a remote
      aspartate. Perturbations of single residues in this network, both inside and
      outside the interaction surface, are sufficient to switch the global E2
      interaction selectivity as demonstrated experimentally. Taken together, our
      results indicate a new mechanism to control E2-E3 interaction selectivity at an
      atomic level, highlighting how minimal changes in amino acid side-chain affecting
      the dynamics of intramolecular salt-bridges can be crucial for protein-protein
      interactions. These findings indicate that the widely accepted sequence-structure
      function paradigm should be extended to sequence-structure-dynamics-function
      relationship and open new possibilities for control and fine-tuning of protein
      interaction selectivity.

PMID- 23133360
TI  - Determinants of translation elongation speed and ribosomal profiling biases in
      mouse embryonic stem cells.
AB  - Ribosomal profiling is a promising approach with increasing popularity for
      studying translation. This approach enables monitoring the ribosomal density
      along genes at a resolution of single nucleotides.In this study, we focused on
      ribosomal density profiles of mouse embryonic stem cells. Our analysis suggests,
      for the first time, that even in mammals such as M. musculus the elongation speed
      is significantly and directly affected by determinants of the coding sequence
      such as: 1) the adaptation of codons to the tRNA pool; 2) the local mRNA folding
      of the coding sequence; 3) the local charge of amino acids encoded in the codon
      sequence. In addition, our analyses suggest that in general, the translation
      velocity of ribosomes is slower at the beginning of the coding sequence and tends
      to increase downstream.Finally, a comparison of these data to the expected
      biophysical behavior of translation suggests that it suffers from some unknown
      biases. Specifically, the ribosomal flux measured on the experimental data
      increases along the coding sequence; however, according to any biophysical model
      of ribosomal movement lacking internal initiation sites, the flux is expected to
      remain constant or decrease. Thus, developing experimental and/or statistical
      methods for understanding, detecting and dealing with such biases is of high
      importance.

PMID- 23133361
TI  - A mathematical model of CR3/TLR2 crosstalk in the context of Francisella
      tularensis infection.
AB  - Complement Receptor 3 (CR3) and Toll-like Receptor 2 (TLR2) are pattern
      recognition receptors expressed on the surface of human macrophages. Although
      these receptors are essential components for recognition by the innate immune
      system, pathogen coordinated crosstalk between them can suppress the production
      of protective cytokines and promote infection. Recognition of the virulent Schu
      S4 strain of the intracellular pathogen Francisella tularensis by host
      macrophages involves CR3/TLR2 crosstalk. Although experimental data provide
      evidence that Lyn kinase and PI3K are essential components of the CR3 pathway
      that influences TLR2 activity, additional responsible upstream signaling
      components remain unknown. In this paper we construct a mathematical model of CR3
      and TLR2 signaling in response to F. tularensis. After demonstrating that the
      model is consistent with experimental results we perform numerical simulations to
      evaluate the contributions that Akt and Ras-GAP make to ERK inhibition. The model
      confirms that phagocytosis-associated changes in the composition of the cell
      membrane can inhibit ERK activity and predicts that Akt and Ras-GAP synergize to
      inhibit ERK.

PMID- 23133362
TI  - Impact of stoichiometry representation on simulation of genotype-phenotype
      relationships in metabolic networks.
AB  - Genome-scale metabolic networks provide a comprehensive structural framework for
      modeling genotype-phenotype relationships through flux simulations. The solution
      space for the metabolic flux state of the cell is typically very large and
      optimization-based approaches are often necessary for predicting the active
      metabolic state under specific environmental conditions. The objective function
      to be used in such optimization algorithms is directly linked with the biological
      hypothesis underlying the model and therefore it is one of the most relevant
      parameters for successful modeling. Although linear combination of selected
      fluxes is widely used for formulating metabolic objective functions, we show that
      the resulting optimization problem is sensitive towards stoichiometry
      representation of the metabolic network. This undesirable sensitivity leads to
      different simulation results when using numerically different but biochemically
      equivalent stoichiometry representations and thereby makes biological
      interpretation intrinsically subjective and ambiguous. We hereby propose a new
      method, Minimization of Metabolites Balance (MiMBl), which decouples the
      artifacts of stoichiometry representation from the formulation of the desired
      objective functions, by casting objective functions using metabolite turnovers
      rather than fluxes. By simulating perturbed metabolic networks, we demonstrate
      that the use of stoichiometry representation independent algorithms is
      fundamental for unambiguously linking modeling results with biological
      interpretation. For example, MiMBl allowed us to expand the scope of metabolic
      modeling in elucidating the mechanistic basis of several genetic interactions in
      Saccharomyces cerevisiae.

PMID- 23133363
TI  - Music in our ears: the biological bases of musical timbre perception.
AB  - Timbre is the attribute of sound that allows humans and other animals to
      distinguish among different sound sources. Studies based on psychophysical
      judgments of musical timbre, ecological analyses of sound's physical
      characteristics as well as machine learning approaches have all suggested that
      timbre is a multifaceted attribute that invokes both spectral and temporal sound
      features. Here, we explored the neural underpinnings of musical timbre. We used a
      neuro-computational framework based on spectro-temporal receptive fields,
      recorded from over a thousand neurons in the mammalian primary auditory cortex as
      well as from simulated cortical neurons, augmented with a nonlinear classifier.
      The model was able to perform robust instrument classification irrespective of
      pitch and playing style, with an accuracy of 98.7%. Using the same front end, the
      model was also able to reproduce perceptual distance judgments between timbres as
      perceived by human listeners. The study demonstrates that joint spectro-temporal
      features, such as those observed in the mammalian primary auditory cortex, are
      critical to provide the rich-enough representation necessary to account for
      perceptual judgments of timbre by human listeners, as well as recognition of
      musical instruments.

PMID- 23133364
TI  - pH-Dependent conformational changes in proteins and their effect on experimental
      pK(a)s: the case of Nitrophorin 4.
AB  - The acid-base behavior of amino acids is an important subject of study due to
      their prominent role in enzyme catalysis, substrate binding and protein
      structure. Due to interactions with the protein environment, their pK(a)s can be
      shifted from their solution values and, if a protein has two stable
      conformations, it is possible for a residue to have different "microscopic",
      conformation-dependent pK(a) values. In those cases, interpretation of
      experimental measurements of the pK(a) is complicated by the coupling between pH,
      protonation state and protein conformation. We explored these issues using
      Nitrophorin 4 (NP4), a protein that releases NO in a pH sensitive manner. At pH
      5.5 NP4 is in a closed conformation where NO is tightly bound, while at pH 7.5
      Asp30 becomes deprotonated, causing the conformation to change to an open state
      from which NO can easily escape. Using constant pH molecular dynamics we found
      two distinct microscopic Asp30 pK(a)s: 8.5 in the closed structure and 4.3 in the
      open structure. Using a four-state model, we then related the obtained
      microscopic values to the experimentally observed "apparent" pK(a), obtaining a
      value of 6.5, in excellent agreement with experimental data. This value must be
      interpreted as the pH at which the closed to open population transition takes
      place. More generally, our results show that it is possible to relate microscopic
      structure dependent pKa values to experimentally observed ensemble dependent
      apparent pK(a)s and that the insight gained in the relatively simple case of NP4
      can be useful in several more complex cases involving a pH dependent transition,
      of great biochemical interest.

PMID- 23133365
TI  - Phenomenological model for predicting the catabolic potential of an arbitrary
      nutrient.
AB  - The ability of microbial species to consume compounds found in the environment to
      generate commercially-valuable products has long been exploited by humanity. The
      untapped, staggering diversity of microbial organisms offers a wealth of
      potential resources for tackling medical, environmental, and energy challenges.
      Understanding microbial metabolism will be crucial to many of these potential
      applications. Thermodynamically-feasible metabolic reconstructions can be used,
      under some conditions, to predict the growth rate of certain microbes using
      constraint-based methods. While these reconstructions are powerful, they are
      still cumbersome to build and, because of the complexity of metabolic networks,
      it is hard for researchers to gain from these reconstructions an understanding of
      why a certain nutrient yields a given growth rate for a given microbe. Here, we
      present a simple model of biomass production that accurately reproduces the
      predictions of thermodynamically-feasible metabolic reconstructions. Our model
      makes use of only: i) a nutrient's structure and function, ii) the presence of a
      small number of enzymes in the organism, and iii) the carbon flow in pathways
      that catabolize nutrients. When applied to test organisms, our model allows us to
      predict whether a nutrient can be a carbon source with an accuracy of about 90%
      with respect to in silico experiments. In addition, our model provides excellent
      predictions of whether a medium will produce more or less growth than another
      (p<10(-6)) and good predictions of the actual value of the in silico biomass
      production.

PMID- 23133366
TI  - Mesoscopic model of actin-based propulsion.
AB  - Two theoretical models dominate current understanding of actin-based propulsion:
      microscopic polymerization ratchet model predicts that growing and writhing actin
      filaments generate forces and movements, while macroscopic elastic propulsion
      model suggests that deformation and stress of growing actin gel are responsible
      for the propulsion. We examine both experimentally and computationally the 2D
      movement of ellipsoidal beads propelled by actin tails and show that neither of
      the two models can explain the observed bistability of the orientation of the
      beads. To explain the data, we develop a 2D hybrid mesoscopic model by
      reconciling these two models such that individual actin filaments undergoing
      nucleation, elongation, attachment, detachment and capping are embedded into the
      boundary of a node-spring viscoelastic network representing the macroscopic actin
      gel. Stochastic simulations of this 'in silico' actin network show that the
      combined effects of the macroscopic elastic deformation and microscopic ratchets
      can explain the observed bistable orientation of the actin-propelled ellipsoidal
      beads. To test the theory further, we analyze observed distribution of the
      curvatures of the trajectories and show that the hybrid model's predictions fit
      the data. Finally, we demonstrate that the model can explain both concave-up and
      concave-down force-velocity relations for growing actin networks depending on the
      characteristic time scale and network recoil. To summarize, we propose that both
      microscopic polymerization ratchets and macroscopic stresses of the deformable
      actin network are responsible for the force and movement generation.

PMID- 23133367
TI  - Structural insights into the inhibition of actin-capping protein by interactions
      with phosphatidic acid and phosphatidylinositol (4,5)-bisphosphate.
AB  - The actin cytoskeleton is a dynamic structure that coordinates numerous
      fundamental processes in eukaryotic cells. Dozens of actin-binding proteins are
      known to be involved in the regulation of actin filament organization or turnover
      and many of these are stimulus-response regulators of phospholipid signaling. One
      of these proteins is the heterodimeric actin-capping protein (CP) which binds the
      barbed end of actin filaments with high affinity and inhibits both addition and
      loss of actin monomers at this end. The ability of CP to bind filaments is
      regulated by signaling phospholipids, which inhibit the activity of CP; however,
      the exact mechanism of this regulation and the residues on CP responsible for
      lipid interactions is not fully resolved. Here, we focus on the interaction of CP
      with two signaling phospholipids, phosphatidic acid (PA) and phosphatidylinositol
      (4,5)-bisphosphate (PIP(2)). Using different methods of computational biology
      such as homology modeling, molecular docking and coarse-grained molecular
      dynamics, we uncovered specific modes of high affinity interaction between
      membranes containing PA/phosphatidylcholine (PC) and plant CP, as well as between
      PIP(2)/PC and animal CP. In particular, we identified differences in the binding
      of membrane lipids by animal and plant CP, explaining previously published
      experimental results. Furthermore, we pinpoint the critical importance of the C
      terminal part of plant CPalpha subunit for CP-membrane interactions. We prepared
      a GST-fusion protein for the C-terminal domain of plant alpha subunit and
      verified this hypothesis with lipid-binding assays in vitro.

PMID- 23133369
TI  - Burden of communicable disease among the native and repatriating Afghans.

PMID- 23133368
TI  - Decorrelation of neural-network activity by inhibitory feedback.
AB  - Correlations in spike-train ensembles can seriously impair the encoding of
      information by their spatio-temporal structure. An inevitable source of
      correlation in finite neural networks is common presynaptic input to pairs of
      neurons. Recent studies demonstrate that spike correlations in recurrent neural
      networks are considerably smaller than expected based on the amount of shared
      presynaptic input. Here, we explain this observation by means of a linear network
      model and simulations of networks of leaky integrate-and-fire neurons. We show
      that inhibitory feedback efficiently suppresses pairwise correlations and, hence,
      population-rate fluctuations, thereby assigning inhibitory neurons the new role
      of active decorrelation. We quantify this decorrelation by comparing the
      responses of the intact recurrent network (feedback system) and systems where the
      statistics of the feedback channel is perturbed (feedforward system).
      Manipulations of the feedback statistics can lead to a significant increase in
      the power and coherence of the population response. In particular, neglecting
      correlations within the ensemble of feedback channels or between the external
      stimulus and the feedback amplifies population-rate fluctuations by orders of
      magnitude. The fluctuation suppression in homogeneous inhibitory networks is
      explained by a negative feedback loop in the one-dimensional dynamics of the
      compound activity. Similarly, a change of coordinates exposes an effective
      negative feedback loop in the compound dynamics of stable excitatory-inhibitory
      networks. The suppression of input correlations in finite networks is explained
      by the population averaged correlations in the linear network model: In purely
      inhibitory networks, shared-input correlations are canceled by negative spike
      train correlations. In excitatory-inhibitory networks, spike-train correlations
      are typically positive. Here, the suppression of input correlations is not a
      result of the mere existence of correlations between excitatory (E) and
      inhibitory (I) neurons, but a consequence of a particular structure of
      correlations among the three possible pairings (EE, EI, II).

PMID- 23133370
TI  - Transcription factor Amr1 induces melanin biosynthesis and suppresses virulence
      in Alternaria brassicicola.
AB  - Alternaria brassicicola is a successful saprophyte and necrotrophic plant
      pathogen. Several A. brassicicola genes have been characterized as affecting
      pathogenesis of Brassica species. To study regulatory mechanisms of pathogenesis,
      we mined 421 genes in silico encoding putative transcription factors in a machine
      annotated, draft genome sequence of A. brassicicola. In this study, targeted gene
      disruption mutants for 117 of the transcription factor genes were produced and
      screened. Three of these genes were associated with pathogenesis. Disruption
      mutants of one gene (AbPacC) were nonpathogenic and another gene (AbVf8) caused
      lesions less than half the diameter of wild-type lesions. Unexpectedly, mutants
      of the third gene, Amr1, caused lesions with a two-fold larger diameter than the
      wild type and complementation mutants. Amr1 is a homolog of Cmr1, a transcription
      factor that regulates melanin biosynthesis in several fungi. We created gene
      deletion mutants of Deltaamr1 and characterized their phenotypes. The Deltaamr1
      mutants used pectin as a carbon source more efficiently than the wild type, were
      melanin-deficient, and more sensitive to UV light and glucanase digestion. The
      AMR1 protein was localized in the nuclei of hyphae and in highly melanized
      conidia during the late stage of plant pathogenesis. RNA-seq analysis revealed
      that three genes in the melanin biosynthesis pathway, along with the deleted Amr1
      gene, were expressed at low levels in the mutants. In contrast, many hydrolytic
      enzyme-coding genes were expressed at higher levels in the mutants than in the
      wild type during pathogenesis. The results of this study suggested that a gene
      important for survival in nature negatively affected virulence, probably by a
      less efficient use of plant cell-wall materials. We speculate that the functions
      of the Amr1 gene are important to the success of A. brassicicola as a competitive
      saprophyte and plant parasite.

PMID- 23133371
TI  - Niclosamide is a proton carrier and targets acidic endosomes with broad antiviral
      effects.
AB  - Viruses use a limited set of host pathways for infection. These pathways
      represent bona fide antiviral targets with low likelihood of viral resistance. We
      identified the salicylanilide niclosamide as a broad range antiviral agent
      targeting acidified endosomes. Niclosamide is approved for human use against
      helminthic infections, and has anti-neoplastic and antiviral effects. Its mode of
      action is unknown. Here, we show that niclosamide, which is a weak lipophilic
      acid inhibited infection with pH-dependent human rhinoviruses (HRV) and influenza
      virus. Structure-activity studies showed that antiviral efficacy and
      endolysosomal pH neutralization co-tracked, and acidification of the
      extracellular medium bypassed the virus entry block. Niclosamide did not affect
      the vacuolar H(+)-ATPase, but neutralized coated vesicles or synthetic liposomes,
      indicating a proton carrier mode-of-action independent of any protein target.
      This report demonstrates that physico-chemical interference with host pathways
      has broad range antiviral effects, and provides a proof of concept for the
      development of host-directed antivirals.

PMID- 23133372
TI  - Deciphering the acylation pattern of Yersinia enterocolitica lipid A.
AB  - Pathogenic bacteria may modify their surface to evade the host innate immune
      response. Yersinia enterocolitica modulates its lipopolysaccharide (LPS) lipid A
      structure, and the key regulatory signal is temperature. At 21 degrees C, lipid A
      is hexa-acylated and may be modified with aminoarabinose or palmitate. At 37
      degrees C, Y. enterocolitica expresses a tetra-acylated lipid A consistent with
      the 3'-O-deacylation of the molecule. In this work, by combining genetic and mass
      spectrometric analysis, we establish that Y. enterocolitica encodes a lipid A
      deacylase, LpxR, responsible for the lipid A structure observed at 37 degrees C.
      Western blot analyses indicate that LpxR exhibits latency at 21 degrees C,
      deacylation of lipid A is not observed despite the expression of LpxR in the
      membrane. Aminoarabinose-modified lipid A is involved in the latency. 3-D
      modelling, docking and site-directed mutagenesis experiments showed that LpxR D31
      reduces the active site cavity volume so that aminoarabinose containing Kdo(2)
      lipid A cannot be accommodated and, therefore, not deacylated. Our data revealed
      that the expression of lpxR is negatively controlled by RovA and PhoPQ which are
      necessary for the lipid A modification with aminoarabinose. Next, we investigated
      the role of lipid A structural plasticity conferred by LpxR on the
      expression/function of Y. enterocolitica virulence factors. We present evidence
      that motility and invasion of eukaryotic cells were reduced in the lpxR mutant
      grown at 21 degrees C. Mechanistically, our data revealed that the expressions of
      flhDC and rovA, regulators controlling the flagellar regulon and invasin
      respectively, were down-regulated in the mutant. In contrast, the levels of the
      virulence plasmid (pYV)-encoded virulence factors Yops and YadA were not affected
      in the lpxR mutant. Finally, we establish that the low inflammatory response
      associated to Y. enterocolitica infections is the sum of the anti-inflammatory
      action exerted by pYV-encoded YopP and the reduced activation of the LPS receptor
      by a LpxR-dependent deacylated LPS.

PMID- 23133373
TI  - The genome of the obligate intracellular parasite Trachipleistophora hominis: new
      insights into microsporidian genome dynamics and reductive evolution.
AB  - The dynamics of reductive genome evolution for eukaryotes living inside other
      eukaryotic cells are poorly understood compared to well-studied model systems
      involving obligate intracellular bacteria. Here we present 8.5 Mb of sequence
      from the genome of the microsporidian Trachipleistophora hominis, isolated from
      an HIV/AIDS patient, which is an outgroup to the smaller compacted-genome species
      that primarily inform ideas of evolutionary mode for these enormously successful
      obligate intracellular parasites. Our data provide detailed information on the
      gene content, genome architecture and intergenic regions of a larger
      microsporidian genome, while comparative analyses allowed us to infer genomic
      features and metabolism of the common ancestor of the species investigated. Gene
      length reduction and massive loss of metabolic capacity in the common ancestor
      was accompanied by the evolution of novel microsporidian-specific protein
      families, whose conservation among microsporidians, against a background of
      reductive evolution, suggests they may have important functions in their
      parasitic lifestyle. The ancestor had already lost many metabolic pathways but
      retained glycolysis and the pentose phosphate pathway to provide cytosolic ATP
      and reduced coenzymes, and it had a minimal mitochondrion (mitosome) making Fe-S
      clusters but not ATP. It possessed bacterial-like nucleotide transport proteins
      as a key innovation for stealing host-generated ATP, the machinery for RNAi, key
      elements of the early secretory pathway, canonical eukaryotic as well as
      microsporidian-specific regulatory elements, a diversity of repetitive and
      transposable elements, and relatively low average gene density. Microsporidian
      genome evolution thus appears to have proceeded in at least two major steps: an
      ancestral remodelling of the proteome upon transition to intracellular parasitism
      that involved reduction but also selective expansion, followed by a secondary
      compaction of genome architecture in some, but not all, lineages.

PMID- 23133374
TI  - Design and evaluation of meningococcal vaccines through structure-based
      modification of host and pathogen molecules.
AB  - Neisseria meningitis remains a leading cause of sepsis and meningitis, and
      vaccines are required to prevent infections by this important human pathogen.
      Factor H binding protein (fHbp) is a key antigen that elicits protective immunity
      against the meningococcus and recruits the host complement regulator, fH. As the
      high affinity interaction between fHbp and fH could impair immune responses, we
      sought to identify non-functional fHbps that could act as effective immunogens.
      This was achieved by alanine substitution of fHbps from all three variant groups
      (V1, V2 and V3 fHbp) of the protein; while some residues affected fH binding in
      each variant group, the distribution of key amino underlying the interaction with
      fH differed between the V1, V2 and V3 proteins. The atomic structure of V3 fHbp
      in complex with fH and of the C-terminal barrel of V2 fHbp provide explanations
      to the differences in the precise nature of their interactions with fH, and the
      instability of the V2 protein. To develop transgenic models to assess the
      efficacy of non-functional fHbps, we determined the structural basis of the low
      level of interaction between fHbp and murine fH; in addition to changes in amino
      acids in the fHbp binding site, murine fH has a distinct conformation compared
      with the human protein that would sterically inhibit binding to fHbp. Non
      functional V1 fHbps were further characterised by binding and structural studies,
      and shown in non-transgenic and transgenic mice (expressing chimeric fH that
      binds fHbp and precisely regulates complement system) to retain their
      immunogenicity. Our findings provide a catalogue of non-functional fHbps from all
      variant groups that can be included in new generation meningococcal vaccines, and
      establish proof-in-principle for clinical studies to compare their efficacy with
      wild-type fHbps.

PMID- 23133375
TI  - Neuroimmunological blood brain barrier opening in experimental cerebral malaria.
AB  - Plasmodium falciparum malaria is responsible for nearly one million annual deaths
      worldwide. Because of the difficulty in monitoring the pathogenesis of cerebral
      malaria in humans, we conducted a study in various mouse models to better
      understand disease progression in experimental cerebral malaria (ECM). We
      compared the effect on the integrity of the blood brain barrier (BBB) and the
      histopathology of the brain of P. berghei ANKA, a known ECM model, P. berghei
      NK65, generally thought not to induce ECM, P. yoelii 17XL, originally reported to
      induce human cerebral malaria-like histopathology, and P. yoelii YM. As expected,
      P. berghei ANKA infection caused neurological signs, cerebral hemorrhages, and
      BBB dysfunction in CBA/CaJ and Swiss Webster mice, while Balb/c and A/J mice were
      resistant. Surprisingly, PbNK induced ECM in CBA/CaJ mice, while all other mice
      were resistant. P. yoelii 17XL and P. yoelii YM caused lethal hyperparasitemia in
      all mouse strains; histopathological alterations, BBB dysfunction, or
      neurological signs were not observed. Intravital imaging revealed that infected
      erythrocytes containing mature parasites passed slowly through capillaries making
      intimate contact with the endothelium, but did not arrest. Except for relatively
      rare microhemorrhages, mice with ECM presented no obvious histopathological
      alterations that would explain the widespread disruption of the BBB. Intravital
      imaging did reveal, however, that postcapillary venules, but not capillaries or
      arterioles, from mice with ECM, but not hyperparasitemia, exhibit platelet
      marginalization, extravascular fibrin deposition, CD14 expression, and extensive
      vascular leakage. Blockage of LFA-1 mediated cellular interactions prevented
      leukocyte adhesion, vascular leakage, neurological signs, and death from ECM. The
      endothelial barrier-stabilizing mediators imatinib and FTY720 inhibited vascular
      leakage and neurological signs and prolonged survival to ECM. Thus, it appears
      that neurological signs and coma in ECM are due to regulated opening of
      paracellular-junctional and transcellular-vesicular fluid transport pathways at
      the neuroimmunological BBB.

PMID- 23133376
TI  - Myeloid-related protein-14 contributes to protective immunity in gram-negative
      pneumonia derived sepsis.
AB  - Klebsiella (K.) pneumoniae is a common cause of pneumonia-derived sepsis. Myeloid
      related protein 8 (MRP8, S100A8) and MRP14 (S100A9) are the most abundant
      cytoplasmic proteins in neutrophils. They can form MRP8/14 heterodimers that are
      released upon cell stress stimuli. MRP8/14 reportedly exerts antimicrobial
      activity, but in acute fulminant sepsis models MRP8/14 has been found to
      contribute to organ damage and death. We here determined the role of MRP8/14 in
      K. pneumoniae sepsis originating from the lungs, using an established model
      characterized by gradual growth of bacteria with subsequent dissemination.
      Infection resulted in gradually increasing MRP8/14 levels in lungs and plasma.
      Mrp14 deficient (mrp14(-/-)) mice, unable to form MRP8/14 heterodimers, showed
      enhanced bacterial dissemination accompanied by increased organ damage and a
      reduced survival. Mrp14(-/-) macrophages were reduced in their capacity to
      phagocytose Klebsiella. In addition, recombinant MRP8/14 heterodimers, but not
      MRP8 or MRP14 alone, prevented growth of Klebsiella in vitro through chelation of
      divalent cations. Neutrophil extracellular traps (NETs) prepared from wildtype
      but not from mrp14(-/-) neutrophils inhibited Klebsiella growth; in accordance,
      the capacity of human NETs to kill Klebsiella was strongly impaired by an anti
      MRP14 antibody or the addition of zinc. These results identify MRP8/14 as key
      player in protective innate immunity during Klebsiella pneumonia.

PMID- 23133378
TI  - Fatty acid oxidation is essential for egg production by the parasitic flatworm
      Schistosoma mansoni.
AB  - Schistosomes, parasitic flatworms that cause the neglected tropical disease
      schistosomiasis, have been considered to have an entirely carbohydrate based
      metabolism, with glycolysis playing a dominant role in the adult parasites.
      However, we have discovered a close link between mitochondrial oxygen consumption
      by female schistosomes and their ability to produce eggs. We show that oxygen
      consumption rates (OCR) and egg production are significantly diminished by
      pharmacologic inhibition of carnitine palmitoyl transferase 1 (CPT1), which
      catalyzes a rate limiting step in fatty acid beta-oxidation (FAO) and by genetic
      loss of function of acyl CoA synthetase, which complexes with CPT1 and activates
      long chain FA for use in FAO, and of acyl CoA dehydrogenase, which catalyzes the
      first step in FAO within mitochondria. Declines in OCR and egg production
      correlate with changes in a network of lipid droplets within cells in a
      specialized reproductive organ, the vitellarium. Our data point to the importance
      of regulated lipid stores and FAO for the compartmentalized process of egg
      production in schistosomes.

PMID- 23133379
TI  - Glycoprotein N of human cytomegalovirus protects the virus from neutralizing
      antibodies.
AB  - Herpes viruses persist in the infected host and are transmitted between hosts in
      the presence of a fully functional humoral immune response, suggesting that they
      can evade neutralization by antiviral antibodies. Human cytomegalovirus (HCMV)
      encodes a number of polymorphic highly glycosylated virion glycoproteins (g),
      including the essential envelope glycoprotein, gN. We have tested the hypothesis
      that glycosylation of gN contributes to resistance of the virus to neutralizing
      antibodies. Recombinant viruses carrying deletions in serine/threonine rich
      sequences within the glycosylated surface domain of gN were constructed in the
      genetic background of HCMV strain AD169. The deletions had no influence on the
      formation of the gM/gN complex and in vitro replication of the respective viruses
      compared to the parent virus. The gN-truncated viruses were significantly more
      susceptible to neutralization by a gN-specific monoclonal antibody and in
      addition by a number of gB- and gH-specific monoclonal antibodies. Sera from
      individuals previously infected with HCMV also more efficiently neutralized gN
      truncated viruses. Immunization of mice with viruses that expressed the truncated
      forms of gN resulted in significantly higher serum neutralizing antibody titers
      against the homologous strain that was accompanied by increased antibody titers
      against known neutralizing epitopes on gB and gH. Importantly, neutralization
      activity of sera from animals immunized with gN-truncated virus did not exhibit
      enhanced neutralizing activity against the parental wild type virus carrying the
      fully glycosylated wild type gN. Our results indicate that the extensive
      glycosylation of gN could represent a potentially important mechanism by which
      HCMV neutralization by a number of different antibody reactivities can be
      inhibited.

PMID- 23133380
TI  - Ustilago maydis: dissecting the molecular interface between pathogen and plant.

PMID- 23133377
TI  - Targeted restoration of the intestinal microbiota with a simple, defined
      bacteriotherapy resolves relapsing Clostridium difficile disease in mice.
AB  - Relapsing C. difficile disease in humans is linked to a pathological imbalance
      within the intestinal microbiota, termed dysbiosis, which remains poorly
      understood. We show that mice infected with epidemic C. difficile (genotype
      027/BI) develop highly contagious, chronic intestinal disease and persistent
      dysbiosis characterized by a distinct, simplified microbiota containing
      opportunistic pathogens and altered metabolite production. Chronic C. difficile
      027/BI infection was refractory to vancomycin treatment leading to relapsing
      disease. In contrast, treatment of C. difficile 027/BI infected mice with feces
      from healthy mice rapidly restored a diverse, healthy microbiota and resolved C.
      difficile disease and contagiousness. We used this model to identify a simple
      mixture of six phylogenetically diverse intestinal bacteria, including novel
      species, which can re-establish a health-associated microbiota and clear C.
      difficile 027/BI infection from mice. Thus, targeting a dysbiotic microbiota with
      a defined mixture of phylogenetically diverse bacteria can trigger major shifts
      in the microbial community structure that displaces C. difficile and, as a
      result, resolves disease and contagiousness. Further, we demonstrate a rational
      approach to harness the therapeutic potential of health-associated microbial
      communities to treat C. difficile disease and potentially other forms of
      intestinal dysbiosis.

PMID- 23133381
TI  - Post-transcriptional regulation of the Sef1 transcription factor controls the
      virulence of Candida albicans in its mammalian host.
AB  - The yeast Candida albicans transitions between distinct lifestyles as a normal
      component of the human gastrointestinal microbiome and the most common agent of
      disseminated fungal disease. We previously identified Sef1 as a novel Cys(6)Zn(2)
      DNA binding protein that plays an essential role in C. albicans virulence by
      activating the transcription of iron uptake genes in iron-poor environments such
      as the host bloodstream and internal organs. Conversely, in the iron-replete
      gastrointestinal tract, persistence as a commensal requires the transcriptional
      repressor Sfu1, which represses SEF1 and genes for iron uptake. Here, we describe
      an unexpected, transcription-independent role for Sfu1 in the direct inhibition
      of Sef1 function through protein complex formation and localization in the
      cytoplasm, where Sef1 is destabilized. Under iron-limiting conditions, Sef1 forms
      an alternative complex with the putative kinase, Ssn3, resulting in its
      phosphorylation, nuclear localization, and transcriptional activity. Analysis of
      sfu1 and ssn3 mutants in a mammalian model of disseminated candidiasis indicates
      that these post-transcriptional regulatory mechanisms serve as a means for
      precise titration of C. albicans virulence.

PMID- 23133382
TI  - A Hsp40 chaperone protein interacts with and modulates the cellular distribution
      of the primase protein of human cytomegalovirus.
AB  - Genomic DNA replication is a universal and essential process for all herpesvirus
      including human cytomegalovirus (HCMV). HCMV UL70 protein, which is believed to
      encode the primase activity of the viral DNA replication machinery and is highly
      conserved among herpesviruses, needs to be localized in the nucleus, the site of
      viral DNA synthesis. No host factors that facilitate the nuclear import of UL70
      have been reported. In this study, we provided the first direct evidence that
      UL70 specifically interacts with a highly conserved and ubiquitously expressed
      member of the heat shock protein Hsp40/DNAJ family, DNAJB6, which is expressed as
      two isoforms, a and b, as a result of alternative splicing. The interaction of
      UL70 with a common region of DNAJB6a and b was identified by both a two hybrid
      screen in yeast and coimmunoprecipitation in human cells. In transfected cells,
      UL70 was primarily co-localized with DNAJB6a in the nuclei and with DNAJB6b in
      the cytoplasm, respectively. The nuclear import of UL70 was increased in cells in
      which DNAJB6a was up-regulated or DNAJB6b was down-regulated, and was reduced in
      cells in which DNAJB6a was down-regulated or DNAJB6b was up-regulated.
      Furthermore, the level of viral DNA synthesis and progeny production was
      increased in cells in which DNAJB6a was up-regulated or DNAJB6b was down
      regulated, and was reduced in cells in which DNAJB6a was down-regulated or
      DNAJB6b was up-regulated. Thus, DNAJB6a and b appear to enhance the nuclear
      import and cytoplasmic accumulation of UL70, respectively. Our results also
      suggest that the relative expression levels of DNAJB6 isoforms may play a key
      role in regulating the cellular localization of UL70, leading to modulation of
      HCMV DNA synthesis and lytic infection.

PMID- 23133383
TI  - Prion pathogenesis is faithfully reproduced in cerebellar organotypic slice
      cultures.
AB  - Prions cause neurodegeneration in vivo, yet prion-infected cultured cells do not
      show cytotoxicity. This has hampered mechanistic studies of prion-induced
      neurodegeneration. Here we report that prion-infected cultured organotypic
      cerebellar slices (COCS) experienced progressive spongiform neurodegeneration
      closely reproducing prion disease, with three different prion strains giving rise
      to three distinct patterns of prion protein deposition. Neurodegeneration did not
      occur when PrP was genetically removed from neurons, and a comprehensive
      pharmacological screen indicated that neurodegeneration was abrogated by
      compounds known to antagonize prion replication. Prion infection of COCS and mice
      led to enhanced fodrin cleavage, suggesting the involvement of calpains or
      caspases in pathogenesis. Accordingly, neurotoxicity and fodrin cleavage were
      prevented by calpain inhibitors but not by caspase inhibitors, whereas prion
      replication proceeded unimpeded. Hence calpain inhibition can uncouple prion
      replication from its neurotoxic sequelae. These data validate COCS as a powerful
      model system that faithfully reproduces most morphological hallmarks of prion
      infections. The exquisite accessibility of COCS to pharmacological manipulations
      was instrumental in recognizing the role of calpains in neurotoxicity, and
      significantly extends the collection of tools necessary for rigorously dissecting
      prion pathogenesis.

PMID- 23133384
TI  - A heparan-dependent herpesvirus targets the olfactory neuroepithelium for host
      entry.
AB  - Herpesviruses are ubiquitous pathogens that cause much disease. The difficulty of
      clearing their established infections makes host entry an important target for
      control. However, while herpesviruses have been studied extensively in vitro, how
      they cross differentiated mucus-covered epithelia in vivo is unclear. To
      establish general principles we tracked host entry by Murid Herpesvirus-4 (MuHV
      4), a lymphotropic rhadinovirus related to the Kaposi's Sarcoma-associated
      Herpesvirus. Spontaneously acquired virions targeted the olfactory
      neuroepithelium. Like many herpesviruses, MuHV-4 binds to heparan sulfate (HS),
      and virions unable to bind HS showed poor host entry. While the respiratory
      epithelium expressed only basolateral HS and was bound poorly by incoming
      virions, the neuroepithelium also displayed HS on its apical neuronal cilia and
      was bound strongly. Incoming virions tracked down the neuronal cilia, and either
      infected neurons or reached the underlying microvilli of the adjacent glial
      (sustentacular) cells and infected them. Thus the olfactory neuroepithelium
      provides an important and complex site of HS-dependent herpesvirus uptake.

PMID- 23133385
TI  - Identification of two Legionella pneumophila effectors that manipulate host
      phospholipids biosynthesis.
AB  - The intracellular pathogen Legionella pneumophila translocates a large number of
      effector proteins into host cells via the Icm/Dot type-IVB secretion system. Some
      of these effectors were shown to cause lethal effect on yeast growth. Here we
      characterized one such effector (LecE) and identified yeast suppressors that
      reduced its lethal effect. The LecE lethal effect was found to be suppressed by
      the over expression of the yeast protein Dgk1 a diacylglycerol (DAG) kinase
      enzyme and by a deletion of the gene encoding for Pah1 a phosphatidic acid (PA)
      phosphatase that counteracts the activity of Dgk1. Genetic analysis using yeast
      deletion mutants, strains expressing relevant yeast genes and point mutations
      constructed in the Dgk1 and Pah1 conserved domains indicated that LecE functions
      similarly to the Nem1-Spo7 phosphatase complex that activates Pah1 in yeast. In
      addition, by using relevant yeast genetic backgrounds we examined several L.
      pneumophila effectors expected to be involved in phospholipids biosynthesis and
      identified an effector (LpdA) that contains a phospholipase-D (PLD) domain which
      caused lethal effect only in a dgk1 deletion mutant of yeast. Additionally, LpdA
      was found to enhance the lethal effect of LecE in yeast cells, a phenomenon which
      was found to be dependent on its PLD activity. Furthermore, to determine whether
      LecE and LpdA affect the levels or distribution of DAG and PA in-vivo in
      mammalian cells, we utilized fluorescent DAG and PA biosensors and validated the
      notion that LecE and LpdA affect the in-vivo levels and distribution of DAG and
      PA, respectively. Finally, we examined the intracellular localization of both
      LecE and LpdA in human macrophages during L. pneumophila infection and found that
      both effectors are localized to the bacterial phagosome. Our results suggest that
      L. pneumophila utilize at least two effectors to manipulate important steps in
      phospholipids biosynthesis.

PMID- 23133386
TI  - Identification of a novel splice variant form of the influenza A virus M2 ion
      channel with an antigenically distinct ectodomain.
AB  - Segment 7 of influenza A virus produces up to four mRNAs. Unspliced transcripts
      encode M1, spliced mRNA2 encodes the M2 ion channel, while protein products from
      spliced mRNAs 3 and 4 have not previously been identified. The M2 protein plays
      important roles in virus entry and assembly, and is a target for antiviral drugs
      and vaccination. Surprisingly, M2 is not essential for virus replication in a
      laboratory setting, although its loss attenuates the virus. To better understand
      how IAV might replicate without M2, we studied the reversion mechanism of an M2
      null virus. Serial passage of a virus lacking the mRNA2 splice donor site
      identified a single nucleotide pseudoreverting mutation, which restored growth in
      cell culture and virulence in mice by upregulating mRNA4 synthesis rather than by
      reinstating mRNA2 production. We show that mRNA4 encodes a novel M2-related
      protein (designated M42) with an antigenically distinct ectodomain that can
      functionally replace M2 despite showing clear differences in intracellular
      localisation, being largely retained in the Golgi compartment. We also show that
      the expression of two distinct ion channel proteins is not unique to laboratory
      adapted viruses but, most notably, was also a feature of the 1983 North American
      outbreak of H5N2 highly pathogenic avian influenza virus. In identifying a 14th
      influenza A polypeptide, our data reinforce the unexpectedly high coding capacity
      of the viral genome and have implications for virus evolution, as well as for
      understanding the role of M2 in the virus life cycle.

PMID- 23133387
TI  - Expression of a cryptic secondary sigma factor gene unveils natural competence
      for DNA transformation in Staphylococcus aureus.
AB  - It has long been a question whether Staphylococcus aureus, a major human
      pathogen, is able to develop natural competence for transformation by DNA. We
      previously showed that a novel staphylococcal secondary sigma factor, SigH, was a
      likely key component for competence development, but the corresponding gene
      appeared to be cryptic as its expression could not be detected during growth
      under standard laboratory conditions. Here, we have uncovered two distinct
      mechanisms allowing activation of SigH production in a minor fraction of the
      bacterial cell population. The first is a chromosomal gene duplication
      rearrangement occurring spontaneously at a low frequency [<=10(-5)], generating
      expression of a new chimeric sigH gene. The second involves post-transcriptional
      regulation through an upstream inverted repeat sequence, effectively suppressing
      expression of the sigH gene. Importantly, we have demonstrated for the first time
      that S. aureus cells producing active SigH become competent for transformation by
      plasmid or chromosomal DNA, which requires the expression of SigH-controlled
      competence genes. Additionally, using DNA from the N315 MRSA strain, we
      successfully transferred the full length SCCmecII element through natural
      transformation to a methicillin-sensitive strain, conferring methicillin
      resistance to the resulting S. aureus transformants. Taken together, we propose a
      unique model for staphylococcal competence regulation by SigH that could help
      explain the acquisition of antibiotic resistance genes through horizontal gene
      transfer in this important pathogen.

PMID- 23133388
TI  - Exploring new biological functions of amyloids: bacteria cell agglutination
      mediated by host protein aggregation.
AB  - Antimicrobial proteins and peptides (AMPs) are important effectors of the innate
      immune system that play a vital role in the prevention of infections. Recent
      advances have highlighted the similarity between AMPs and amyloid proteins. Using
      the Eosinophil Cationic Protein as a model, we have rationalized the structure
      activity relationships between amyloid aggregation and antimicrobial activity.
      Our results show how protein aggregation can induce bacteria agglutination and
      cell death. Using confocal and total internal reflection fluorescence microscopy
      we have tracked the formation in situ of protein amyloid-like aggregates at the
      bacteria surface and on membrane models. In both cases, fibrillar aggregates able
      to bind to amyloid diagnostic dyes were detected. Additionally, a single point
      mutation (Ile13 to Ala) can suppress the protein amyloid behavior, abolishing the
      agglutinating activity and impairing the antimicrobial action. The mutant is also
      defective in triggering both leakage and lipid vesicle aggregation. We conclude
      that ECP aggregation at the bacterial surface is essential for its cytotoxicity.
      Hence, we propose here a new prospective biological function for amyloid-like
      aggregates with potential biological relevance.

PMID- 23133389
TI  - Circulating virus load determines the size of bottlenecks in viral populations
      progressing within a host.
AB  - For any organism, population size, and fluctuations thereof, are of primary
      importance in determining the forces driving its evolution. This is particularly
      true for viruses--rapidly evolving entities that form populations with transient
      and explosive expansions alternating with phases of migration, resulting in
      strong population bottlenecks and associated founder effects that increase
      genetic drift. A typical illustration of this pattern is the progression of viral
      disease within a eukaryotic host, where such demographic fluctuations are a key
      factor in the emergence of new variants with altered virulence. Viruses initiate
      replication in one or only a few infection foci, then move through the
      vasculature to seed secondary infection sites and so invade distant organs and
      tissues. Founder effects during this within-host colonization might depend on the
      concentration of infectious units accumulating and circulating in the
      vasculature, as this represents the infection dose reaching new organs or
      "territories". Surprisingly, whether or not the easily measurable circulating
      (plasma) virus load directly drives the size of population bottlenecks during
      host colonization has not been documented in animal viruses, while in plants the
      virus load within the sap has never been estimated. Here, we address this
      important question by monitoring both the virus concentration flowing in host
      plant sap, and the number of viral genomes founding the population in each
      successive new leaf. Our results clearly indicate that the concentration of
      circulating viruses directly determines the size of bottlenecks, which hence
      controls founder effects and effective population size during disease progression
      within a host.

PMID- 23133390
TI  - Histone H1 plays a role in heterochromatin formation and VSG expression site
      silencing in Trypanosoma brucei.
AB  - The African sleeping sickness parasite Trypanosoma brucei evades the host immune
      system through antigenic variation of its variant surface glycoprotein (VSG)
      coat. Although the T. brucei genome contains ~1500 VSGs, only one VSG is
      expressed at a time from one of about 15 subtelomeric VSG expression sites (ESs).
      For antigenic variation to work, not only must the vast VSG repertoire be kept
      silent in a genome that is mainly constitutively transcribed, but the frequency
      of VSG switching must be strictly controlled. Recently it has become clear that
      chromatin plays a key role in silencing inactive ESs, thereby ensuring
      monoallelic expression of VSG. We investigated the role of the linker histone H1
      in chromatin organization and ES regulation in T. brucei. T. brucei histone H1
      proteins have a different domain structure to H1 proteins in higher eukaryotes.
      However, we show that they play a key role in the maintenance of higher order
      chromatin structure in bloodstream form T. brucei as visualised by electron
      microscopy. In addition, depletion of histone H1 results in chromatin becoming
      generally more accessible to endonucleases in bloodstream but not in insect form
      T. brucei. The effect on chromatin following H1 knock-down in bloodstream form T.
      brucei is particularly evident at transcriptionally silent ES promoters, leading
      to 6-8 fold derepression of these promoters. T. brucei histone H1 therefore
      appears to be important for the maintenance of repressed chromatin in bloodstream
      form T. brucei. In particular H1 plays a role in downregulating silent ESs,
      arguing that H1-mediated chromatin functions in antigenic variation in T. brucei.

PMID- 23133391
TI  - Revised phylogeny and novel horizontally acquired virulence determinants of the
      model soft rot phytopathogen Pectobacterium wasabiae SCC3193.
AB  - Soft rot disease is economically one of the most devastating bacterial diseases
      affecting plants worldwide. In this study, we present novel insights into the
      phylogeny and virulence of the soft rot model Pectobacterium sp. SCC3193, which
      was isolated from a diseased potato stem in Finland in the early 1980s. Genomic
      approaches, including proteome and genome comparisons of all sequenced soft rot
      bacteria, revealed that SCC3193, previously included in the species
      Pectobacterium carotovorum, can now be more accurately classified as
      Pectobacterium wasabiae. Together with the recently revised phylogeny of a few P.
      carotovorum strains and an increasing number of studies on P. wasabiae, our work
      indicates that P. wasabiae has been unnoticed but present in potato fields
      worldwide. A combination of genomic approaches and in planta experiments
      identified features that separate SCC3193 and other P. wasabiae strains from the
      rest of soft rot bacteria, such as the absence of a type III secretion system
      that contributes to virulence of other soft rot species. Experimentally
      established virulence determinants include the putative transcriptional regulator
      SirB, two partially redundant type VI secretion systems and two horizontally
      acquired clusters (Vic1 and Vic2), which contain predicted virulence genes.
      Genome comparison also revealed other interesting traits that may be related to
      life in planta or other specific environmental conditions. These traits include a
      predicted benzoic acid/salicylic acid carboxyl methyltransferase of eukaryotic
      origin. The novelties found in this work indicate that soft rot bacteria have a
      reservoir of unknown traits that may be utilized in the poorly understood latent
      stage in planta. The genomic approaches and the comparison of the model strain
      SCC3193 to other sequenced Pectobacterium strains, including the type strain of
      P. wasabiae, provides a solid basis for further investigation of the virulence,
      distribution and phylogeny of soft rot bacteria and, potentially, other bacteria
      as well.

PMID- 23133392
TI  - Topoisomerase II- and condensin-dependent breakage of MEC1ATR-sensitive fragile
      sites occurs independently of spindle tension, anaphase, or cytokinesis.
AB  - Fragile sites are loci of recurrent chromosome breakage in the genome. They are
      found in organisms ranging from bacteria to humans and are implicated in genome
      instability, evolution, and cancer. In budding yeast, inactivation of Mec1, a
      homolog of mammalian ATR, leads to chromosome breakage at fragile sites referred
      to as replication slow zones (RSZs). RSZs are proposed to be homologous to
      mammalian common fragile sites (CFSs) whose stability is regulated by ATR.
      Perturbation during S phase, leading to elevated levels of stalled replication
      forks, is necessary but not sufficient for chromosome breakage at RSZs or CFSs.
      To address the nature of additional event(s) required for the break formation, we
      examined involvement of the currently known or implicated mechanisms of
      endogenous chromosome breakage, including errors in replication fork restart,
      premature mitotic chromosome condensation, spindle tension, anaphase, and
      cytokinesis. Results revealed that chromosome breakage at RSZs is independent of
      the RAD52 epistasis group genes and of TOP3, SGS1, SRS2, MMS4, or MUS81,
      indicating that homologous recombination and other recombination-related
      processes associated with replication fork restart are unlikely to be involved.
      We also found spindle force, anaphase, or cytokinesis to be dispensable. RSZ
      breakage, however, required genes encoding condensin subunits (YCG1, YSC4) and
      topoisomerase II (TOP2). We propose that chromosome break formation at RSZs
      following Mec1 inactivation, a model for mammalian fragile site breakage, is
      mediated by internal chromosomal stress generated during mitotic chromosome
      condensation.

PMID- 23133393
TI  - Variants affecting exon skipping contribute to complex traits.
AB  - DNA variants that affect alternative splicing and the relative quantities of
      different gene transcripts have been shown to be risk alleles for some Mendelian
      diseases. However, for complex traits characterized by a low odds ratio for any
      single contributing variant, very few studies have investigated the contribution
      of splicing variants. The overarching goal of this study is to discover and
      characterize the role that variants affecting alternative splicing may play in
      the genetic etiology of complex traits, which include a significant number of the
      common human diseases. Specifically, we hypothesize that single nucleotide
      polymorphisms (SNPs) in splicing regulatory elements can be characterized in
      silico to identify variants affecting splicing, and that these variants may
      contribute to the etiology of complex diseases as well as the inter-individual
      variability in the ratios of alternative transcripts. We leverage high-throughput
      expression profiling to 1) experimentally validate our in silico predictions of
      skipped exons and 2) characterize the molecular role of intronic genetic
      variations in alternative splicing events in the context of complex human traits
      and diseases. We propose that intronic SNPs play a role as genetic regulators
      within splicing regulatory elements and show that their associated exon skipping
      events can affect protein domains and structure. We find that SNPs we would
      predict to affect exon skipping are enriched among the set of SNPs reported to be
      associated with complex human traits.

PMID- 23133394
TI  - Comparative genomics suggests an independent origin of cytoplasmic
      incompatibility in Cardinium hertigii.
AB  - Terrestrial arthropods are commonly infected with maternally inherited bacterial
      symbionts that cause cytoplasmic incompatibility (CI). In CI, the outcome of
      crosses between symbiont-infected males and uninfected females is reproductive
      failure, increasing the relative fitness of infected females and leading to
      spread of the symbiont in the host population. CI symbionts have profound impacts
      on host genetic structure and ecology and may lead to speciation and the rapid
      evolution of sex determination systems. Cardinium hertigii, a member of the
      Bacteroidetes and symbiont of the parasitic wasp Encarsia pergandiella, is the
      only known bacterium other than the Alphaproteobacteria Wolbachia to cause CI.
      Here we report the genome sequence of Cardinium hertigii cEper1. Comparison with
      the genomes of CI-inducing Wolbachia pipientis strains wMel, wRi, and wPip
      provides a unique opportunity to pinpoint shared proteins mediating host cell
      interaction, including some candidate proteins for CI that have not previously
      been investigated. The genome of Cardinium lacks all major biosynthetic pathways
      but harbors a complete biotin biosynthesis pathway, suggesting a potential role
      for Cardinium in host nutrition. Cardinium lacks known protein secretion systems
      but encodes a putative phage-derived secretion system distantly related to the
      antifeeding prophage of the entomopathogen Serratia entomophila. Lastly, while
      Cardinium and Wolbachia genomes show only a functional overlap of proteins, they
      show no evidence of laterally transferred elements that would suggest common
      ancestry of CI in both lineages. Instead, comparative genomics suggests an
      independent evolution of CI in Cardinium and Wolbachia and provides a novel
      context for understanding the mechanistic basis of CI.

PMID- 23133395
TI  - Morphogenesis and cell fate determination within the adaxial cell equivalence
      group of the zebrafish myotome.
AB  - One of the central questions of developmental biology is how cells of equivalent
      potential-an equivalence group-come to adopt specific cellular fates. In this
      study we have used a combination of live imaging, single cell lineage analyses,
      and perturbation of specific signaling pathways to dissect the specification of
      the adaxial cells of the zebrafish embryo. We show that the adaxial cells are
      myogenic precursors that form a cell fate equivalence group of approximately 20
      cells that consequently give rise to two distinct sub-types of muscle fibers: the
      superficial slow muscle fibers (SSFs) and muscle pioneer cells (MPs),
      distinguished by specific gene expression and cell behaviors. Using a combination
      of live imaging, retrospective and indicative fate mapping, and genetic studies,
      we show that MP and SSF precursors segregate at the beginning of segmentation and
      that they arise from distinct regions along the anterior-posterior (AP) and
      dorsal-ventral (DV) axes of the adaxial cell compartment. FGF signaling restricts
      MP cell fate in the anterior-most adaxial cells in each somite, while BMP
      signaling restricts this fate to the middle of the DV axis. Thus our results
      reveal that the synergistic actions of HH, FGF, and BMP signaling independently
      create a three-dimensional (3D) signaling milieu that coordinates cell fate
      within the adaxial cell equivalence group.

PMID- 23133396
TI  - Embryos of robertsonian translocation carriers exhibit a mitotic interchromosomal
      effect that enhances genetic instability during early development.
AB  - Balanced chromosomal rearrangements represent one of the most common forms of
      genetic abnormality affecting approximately 1 in every 500 (0.2%) individuals.
      Difficulties processing the abnormal chromosomes during meiosis lead to an
      elevated risk of chromosomally abnormal gametes, resulting in high rates of
      miscarriage and/or children with congenital abnormalities. It has also been
      suggested that the presence of chromosome rearrangements may also cause an
      increase in aneuploidy affecting structurally normal chromosomes, due to
      disruption of chromosome alignment on the spindle or disturbance of other factors
      related to meiotic chromosome segregation. The existence of such a phenomenon (an
      inter-chromosomal effect--ICE) remains controversial, with different studies
      presenting contradictory data. The current investigation aimed to demonstrate
      conclusively whether an ICE truly exists. For this purpose a comprehensive
      chromosome screening technique, optimized for analysis of minute amounts of
      tissue, was applied to a unique collection of samples consisting of 283 oocytes
      and early embryos derived from 44 patients carrying chromosome rearrangements. A
      further 5,078 oocytes and embryos, derived from chromosomally normal individuals
      of identical age, provided a robust control group for comparative analysis. A
      highly significant (P = 0.0002) increase in the rate of malsegregation affecting
      structurally normal chromosomes was observed in association with Robertsonian
      translocations. Surprisingly, the ICE was clearly detected in early embryos from
      female carriers, but not in oocytes, indicating the possibility of mitotic rather
      than the previously suggested meiotic origin. These findings have implications
      for our understanding of genetic stability during preimplantation development and
      are of clinical relevance for patients carrying a Robertsonian translocation. The
      results are also pertinent to other situations when cellular mechanisms for
      maintaining genetic fidelity are relaxed and chromosome rearrangements are
      present (e.g. in tumors displaying chromosomal instability).

PMID- 23133397
TI  - Population genomic scan for candidate signatures of balancing selection to guide
      antigen characterization in malaria parasites.
AB  - Acquired immunity in vertebrates maintains polymorphisms in endemic pathogens,
      leading to identifiable signatures of balancing selection. To comprehensively
      survey for genes under such selection in the human malaria parasite Plasmodium
      falciparum, we generated paired-end short-read sequences of parasites in clinical
      isolates from an endemic Gambian population, which were mapped to the 3D7 strain
      reference genome to yield high-quality genome-wide coding sequence data for 65
      isolates. A minority of genes did not map reliably, including the hypervariable
      var, rifin, and stevor families, but 5,056 genes (90.9% of all in the genome) had
      >70% sequence coverage with minimum read depth of 5 for at least 50 isolates, of
      which 2,853 genes contained 3 or more single nucleotide polymorphisms (SNPs) for
      analysis of polymorphic site frequency spectra. Against an overall background of
      negatively skewed frequencies, as expected from historical population expansion
      combined with purifying selection, the outlying minority of genes with signatures
      indicating exceptionally intermediate frequencies were identified. Comparing
      genes with different stage-specificity, such signatures were most common in those
      with peak expression at the merozoite stage that invades erythrocytes. Members of
      clag, PfMC-2TM, surfin, and msp3-like gene families were highly represented, the
      strongest signature being in the msp3-like gene PF10_0355. Analysis of msp3-like
      transcripts in 45 clinical and 11 laboratory adapted isolates grown to merozoite
      containing schizont stages revealed surprisingly low expression of PF10_0355. In
      diverse clonal parasite lines the protein product was expressed in a minority of
      mature schizonts (<1% in most lines and ~10% in clone HB3), and eight sub-clones
      of HB3 cultured separately had an intermediate spectrum of positive frequencies
      (0.9 to 7.5%), indicating phase variable expression of this polymorphic antigen.
      This and other identified targets of balancing selection are now prioritized for
      functional study.

PMID- 23133398
TI  - Disruption of CHTF18 causes defective meiotic recombination in male mice.
AB  - CHTF18 (chromosome transmission fidelity factor 18) is an evolutionarily
      conserved subunit of the Replication Factor C-like complex, CTF18-RLC. CHTF18 is
      necessary for the faithful passage of chromosomes from one daughter cell to the
      next during mitosis in yeast, and it is crucial for germline development in the
      fruitfly. Previously, we showed that mouse Chtf18 is expressed throughout the
      germline, suggesting a role for CHTF18 in mammalian gametogenesis. To determine
      the role of CHTF18 in mammalian germ cell development, we derived mice carrying
      null and conditional mutations in the Chtf18 gene. Chtf18-null males exhibit 5
      fold decreased sperm concentrations compared to wild-type controls, resulting in
      subfertility. Loss of Chtf18 results in impaired spermatogenesis; spermatogenic
      cells display abnormal morphology, and the stereotypical arrangement of cells
      within seminiferous tubules is perturbed. Meiotic recombination is defective and
      homologous chromosomes separate prematurely during prophase I. Repair of DNA
      double-strand breaks is delayed and incomplete; both RAD51 and gammaH2AX persist
      in prophase I. In addition, MLH1 foci are decreased in pachynema. These findings
      demonstrate essential roles for CHTF18 in mammalian spermatogenesis and meiosis,
      and suggest that CHTF18 may function during the double-strand break repair
      pathway to promote the formation of crossovers.

PMID- 23133399
TI  - Trps1 and its target gene Sox9 regulate epithelial proliferation in the
      developing hair follicle and are associated with hypertrichosis.
AB  - Hereditary hypertrichoses are a group of hair overgrowth syndromes that are
      extremely rare in humans. We have previously demonstrated that a position effect
      on TRPS1 is associated with hypertrichosis in humans and mice. To gain insight
      into the functional role of Trps1, we analyzed the late morphogenesis vibrissae
      phenotype of Trps1(Deltagt) mutant mice, which is characterized by follicle
      degeneration after peg downgrowth has been initiated. We found that Trps1
      directly represses expression of the hair follicle stem cell regulator Sox9 to
      control proliferation of the follicle epithelium. Furthermore, we identified a
      copy number variation upstream of SOX9 in a family with hypertrichosis that
      significantly decreases expression of the gene in the hair follicle, providing
      new insights into the long-range regulation of SOX9. Our findings uncover a novel
      transcriptional hierarchy that regulates epithelial proliferation in the
      developing hair follicle and contributes to the pathology of hypertrichosis.

PMID- 23133400
TI  - Long telomeres produced by telomerase-resistant recombination are established
      from a single source and are subject to extreme sequence scrambling.
AB  - Considerable evidence now supports the idea that the moderate telomere
      lengthening produced by recombinational telomere elongation (RTE) in a
      Kluyveromyces lactis telomerase deletion mutant occurs through a roll-and-spread
      mechanism. However, it is unclear whether this mechanism can account for other
      forms of RTE that produce much longer telomeres such as are seen in human
      alternative lengthening of telomere (ALT) cells or in the telomerase-resistant
      type IIR "runaway" RTE such as occurs in the K. lactis stn1-M1 mutant. In this
      study we have used mutationally tagged telomeres to examine the mechanism of RTE
      in an stn1-M1 mutant both with and without telomerase. Our results suggest that
      the establishment stage of the mutant state in newly generated stn1-M1 ter1-Delta
      mutants surprisingly involves a first stage of sudden telomere shortening. Our
      data also show that, as predicted by the roll-and-spread mechanism, all
      lengthened telomeres in a newly established mutant cell commonly emerge from a
      single telomere source. However, in sharp contrast to the RTE of telomerase
      deletion survivors, we show that the RTE of stn1-M1 ter1-Delta cells produces
      telomeres whose sequences undergo continuous intense scrambling via
      recombination. While telomerase was not necessary for the long telomeres in stn1
      M1 cells, its presence during their establishment was seen to interfere with the
      amplification of repeats via recombination, a result consistent with telomerase
      retaining its ability to add repeats during active RTE. Finally, we observed that
      the presence of active mismatch repair or telomerase had important influences on
      telomeric amplification and/or instability.

PMID- 23133401
TI  - Antagonistic gene activities determine the formation of pattern elements along
      the mediolateral axis of the Arabidopsis fruit.
AB  - The Arabidopsis fruit mainly consists of a mature ovary that shows three well
      defined territories that are pattern elements along the mediolateral axis: the
      replum, located at the medial plane of the flower, and the valve and the valve
      margin, both of lateral nature. JAG/FIL activity, which includes the combined
      functions of JAGGED (JAG), FILAMENTOUS FLOWER (FIL), and YABBY3 (YAB3),
      contributes to the formation of the two lateral pattern elements, whereas the
      cooperating genes BREVIPEDICELLUS (BP) and REPLUMLESS (RPL) promote replum
      development. A recent model to explain pattern formation along the mediolateral
      axis hypothesizes that JAG/FIL activity and BP/RPL function as antagonistic
      lateral and medial factors, respectively, which tend to repress each other. In
      this work, we demonstrate the existence of mutual exclusion mechanisms between
      both kinds of factors, and how this determines the formation and size of the
      three territories. Medial factors autonomously constrain lateral factors so that
      they only express outside the replum, and lateral factors negatively regulate the
      medially expressed BP gene in a non-autonomous fashion to ensure correct replum
      development. We also have found that ASYMMETRIC LEAVES1 (AS1), previously shown
      to repress BP both in leaves and ovaries, collaborates with JAG/FIL activity,
      preventing its repression by BP and showing synergistic interactions with JAG/FIL
      activity genes. Therefore AS gene function (the function of the interacting genes
      AS1 and AS2) has been incorporated in the model as a new lateral factor. Our
      model of antagonistic factors provides explanation for mutant fruit phenotypes in
      Arabidopsis and also may help to understand natural variation of fruit shape in
      Brassicaceae and other species, since subtle changes in gene expression may cause
      conspicuous changes in the size of the different tissue types.

PMID- 23133402
TI  - Stimulation of gross chromosomal rearrangements by the human CEB1 and CEB25
      minisatellites in Saccharomyces cerevisiae depends on G-quadruplexes or Cdc13.
AB  - Genomes contain tandem repeats that are at risk of internal rearrangements and a
      threat to genome integrity. Here, we investigated the behavior of the human
      subtelomeric minisatellites HRAS1, CEB1, and CEB25 in Saccharomyces cerevisiae.
      In mitotically growing wild-type cells, these GC-rich tandem arrays stimulate the
      rate of gross chromosomal rearrangements (GCR) by 20, 1,620, and 276,000-fold,
      respectively. In the absence of the Pif1 helicase, known to inhibit GCR by
      telomere addition and to unwind G-quadruplexes, the GCR rate is further increased
      in the presence of CEB1, by 385-fold compared to the pif1Delta control strain.
      The behavior of CEB1 is strongly dependent on its capacity to form G
      quadruplexes, since the treatment of WT cells with the Phen-DC(3) G-quadruplex
      ligand has a 52-fold stimulating effect while the mutation of the G-quadruplex
      forming motif reduced the GCR rate 30-fold in WT and 100-fold in pif1Delta cells.
      The GCR events are telomere additions within CEB1. Differently, the extreme
      stimulation of CEB25 GCR depends on its affinity for Cdc13, which binds the TG
      rich ssDNA telomere overhang. This property confers a biased orientation
      dependent behavior to CEB25, while CEB1 and HRAS1 increase GCR similarly in
      either orientation. Furthermore, we analyzed the minisatellites' distribution in
      the human genome and discuss their potential role to trigger subtelomeric
      rearrangements.

PMID- 23133403
TI  - A dominantly acting murine allele of Mcm4 causes chromosomal abnormalities and
      promotes tumorigenesis.
AB  - Here we report the isolation of a murine model for heritable T cell lymphoblastic
      leukemia/lymphoma (T-ALL) called Spontaneous dominant leukemia (Sdl). Sdl
      heterozygous mice develop disease with a short latency and high penetrance, while
      mice homozygous for the mutation die early during embryonic development. Sdl mice
      exhibit an increase in the frequency of micronucleated reticulocytes, and T-ALLs
      from Sdl mice harbor small amplifications and deletions, including activating
      deletions at the Notch1 locus. Using exome sequencing it was determined that Sdl
      mice harbor a spontaneously acquired mutation in Mcm4 (Mcm4(D573H)). MCM4 is part
      of the heterohexameric complex of MCM2-7 that is important for licensing of DNA
      origins prior to S phase and also serves as the core of the replicative helicase
      that unwinds DNA at replication forks. Previous studies in murine models have
      discovered that genetic reductions of MCM complex levels promote tumor formation
      by causing genomic instability. However, Sdl mice possess normal levels of Mcms,
      and there is no evidence for loss-of-heterozygosity at the Mcm4 locus in Sdl
      leukemias. Studies in Saccharomyces cerevisiae indicate that the Sdl mutation
      produces a biologically inactive helicase. Together, these data support a model
      in which chromosomal abnormalities in Sdl mice result from the ability of
      MCM4(D573H) to incorporate into MCM complexes and render them inactive. Our
      studies indicate that dominantly acting alleles of MCMs can be compatible with
      viability but have dramatic oncogenic consequences by causing chromosomal
      abnormalities.

PMID- 23133404
TI  - A bacteriophage-encoded J-domain protein interacts with the DnaK/Hsp70 chaperone
      and stabilizes the heat-shock factor sigma32 of Escherichia coli.
AB  - The universally conserved J-domain proteins (JDPs) are obligate cochaperone
      partners of the Hsp70 (DnaK) chaperone. They stimulate Hsp70's ATPase activity,
      facilitate substrate delivery, and confer specific cellular localization to
      Hsp70. In this work, we have identified and characterized the first functional
      JDP protein encoded by a bacteriophage. Specifically, we show that the ORFan gene
      057w of the T4-related enterobacteriophage RB43 encodes a bona fide JDP protein,
      named Rki, which specifically interacts with the Escherichia coli host
      multifunctional DnaK chaperone. However, in sharp contrast with the three known
      host JDP cochaperones of DnaK encoded by E. coli, Rki does not act as a generic
      cochaperone in vivo or in vitro. Expression of Rki alone is highly toxic for wild
      type E. coli, but toxicity is abolished in the absence of endogenous DnaK or when
      the conserved J-domain of Rki is mutated. Further in vivo analyses revealed that
      Rki is expressed early after infection by RB43 and that deletion of the rki gene
      significantly impairs RB43 proliferation. Furthermore, we show that mutations in
      the host dnaK gene efficiently suppress the growth phenotype of the RB43 rki
      deletion mutant, thus indicating that Rki specifically interferes with DnaK
      cellular function. Finally, we show that the interaction of Rki with the host
      DnaK chaperone rapidly results in the stabilization of the heat-shock factor
      sigma(32), which is normally targeted for degradation by DnaK. The mechanism by
      which the Rki-dependent stabilization of sigma(32) facilitates RB43 bacteriophage
      proliferation is discussed.

PMID- 23133405
TI  - Interallelic and intergenic incompatibilities of the Prdm9 (Hst1) gene in mouse
      hybrid sterility.
AB  - The Dobzhansky-Muller model of incompatibilities explains reproductive isolation
      between species by incorrect epistatic interactions. Although the mechanisms of
      speciation are of great interest, no incompatibility has been characterized at
      the gene level in mammals. The Hybrid sterility 1 gene (Hst1) participates in the
      arrest of meiosis in F(1) males of certain strains from two Mus musculus
      subspecies, e.g., PWD from M. m. musculus and C57BL/6J (henceforth B6) from M. m.
      domesticus. Hst1 has been identified as a meiotic PR-domain gene (Prdm9) encoding
      histone 3 methyltransferase in the male offspring of PWD females and B6 males,
      (PWD*B6)F(1). To characterize the incompatibilities underlying hybrid sterility,
      we phenotyped reproductive and meiotic markers in males with altered copy numbers
      of Prdm9. A partial rescue of fertility was observed upon removal of the B6
      allele of Prdm9 from the azoospermic (PWD*B6)F(1) hybrids, whereas removing one
      of the two Prdm9 copies in PWD or B6 background had no effect on male
      reproduction. Incompatibility(ies) not involving Prdm9(B6) also acts in the
      (PWD*B6)F(1) hybrids, since the correction of hybrid sterility by Prdm9(B6)
      deletion was not complete. Additions and subtractions of Prdm9 copies, as well as
      allelic replacements, improved meiotic progression and fecundity also in the
      progeny-producing reciprocal (B6*PWD)F(1) males. Moreover, an increased dosage of
      Prdm9 and reciprocal cross enhanced fertility of other sperm-carrying male
      hybrids, (PWD*B6-C3H.Prdm9)F(1), harboring another Prdm9 allele of M. m.
      domesticus origin. The levels of Prdm9 mRNA isoforms were similar in the
      prepubertal testes of all types of F(1) hybrids of PWD with B6 and B6-C3H.Prdm9
      despite their different prospective fertility, but decreased to 53% after removal
      of Prdm9(B6). Therefore, the Prdm9(B6) allele probably takes part in
      posttranscriptional dominant-negative hybrid interaction(s) absent in the
      parental strains.

PMID- 23133406
TI  - Sensitive Marker of the Cisplatin-DNA Interaction: X-Ray Photoelectron
      Spectroscopy of CL.
AB  - The development of cisplatin and Pt-based analogues anticancer agents requires
      knowledge concerning the molecular mechanisms of interaction between such drugs
      with DNA. However, the binding dynamics and kinetics of cisplatin reactions with
      DNA determined by traditional approaches are far from satisfactory. In this
      study, a typical 20-base oligonucleotide (CGTGACAGTTATTGCAGGCG), as a simplified
      model representing DNA, was mixed with cisplatin in different molar ratios and
      incubation time. High-resolution XPS spectra of the core elements C, N, O, P, and
      Cl were recorded to explore the interaction between cisplatin and DNA. From
      deconvoluted Cl spectra we could readily differentiate the covalently bound
      chlorine from ionic chloride species in the cisplatin-oligo complexes, which
      displayed distinct features at various reaction times and ratios. Monitoring the
      magnitude and energy of the photoelectron Cl 2p signal by XPS could act as a
      sensitive marker to probe the interaction dynamics of chemical bonds in the
      reaction of cisplatin with DNA. At 37 degrees C, the optimum incubation time to
      obtain a stable cisplatin-oligo complex lies around 20 hrs. This novel analysis
      technique could have valuable implications to understand the fundamental
      mechanism of cisplatin cytotoxicity and determine the efficiency of the bonds in
      treated cancer cells.

PMID- 23133407
TI  - Distribution and morphology of nitrergic neurons across functional domains of the
      rat primary somatosensory cortex.
AB  - The rat primary somatosensory cortex (S1) is remarkable for its conspicuous
      vertical compartmentalization in barrels and septal columns, which are
      additionally stratified in horizontal layers. Whereas excitatory neurons from
      each of these compartments perform different types of processing, the role of
      interneurons is much less clear. Among the numerous types of GABAergic
      interneurons, those producing nitric oxide (NO) are especially puzzling, since
      this gaseous messenger can modulate neural activity, synaptic plasticity, and
      neurovascular coupling. We used a quantitative morphological approach to
      investigate whether nitrergic interneurons, which might therefore be considered
      both as NO volume diffusers and as elements of local circuitry, display features
      that could relate to barrel cortex architecture. In fixed brain sections,
      nitrergic interneurons can be revealed by histochemical processing for NADPH
      diaphorase (NADPHd). Here, the dendritic arbors of nitrergic neurons from
      different compartments of area S1 were 3D reconstructed from serial 200 MUm thick
      sections, using 100x objective and the Neurolucida system. Standard morphological
      parameters were extracted for all individual arbors and compared across columns
      and layers. Wedge analysis was used to compute dendritic orientation indices.
      Supragranular (SG) layers displayed the highest density of nitrergic neurons,
      whereas layer IV contained nitrergic neurons with largest soma area. The highest
      nitrergic neuronal density was found in septa, where dendrites were previously
      characterized as more extense and ramified than in barrels. Dendritic arbors were
      not confined to the boundaries of the column nor layer of their respective soma,
      being mostly double-tufted and vertically oriented, except in SG layers. These
      data strongly suggest that nitrergic interneurons adapt their morphology to the
      dynamics of processing performed by cortical compartments.

PMID- 23133408
TI  - Adaptation to visual or auditory time intervals modulates the perception of
      visual apparent motion.
AB  - It is debated whether sub-second timing is subserved by a centralized mechanism
      or by the intrinsic properties of task-related neural activity in specific
      modalities (Ivry and Schlerf, 2008). By using a temporal adaptation task, we
      investigated whether adapting to different time intervals conveyed through
      stimuli in different modalities (i.e., frames of a visual Ternus display, visual
      blinking discs, or auditory beeps) would affect the subsequent implicit
      perception of visual timing, i.e., inter-stimulus interval (ISI) between two
      frames in a Ternus display. The Ternus display can induce two percepts of
      apparent motion (AM), depending on the ISI between the two frames: "element
      motion" for short ISIs, in which the endmost disc is seen as moving back and
      forth while the middle disc at the overlapping or central position remains
      stationary; "group motion" for longer ISIs, in which both discs appear to move in
      a manner of lateral displacement as a whole. In Experiment 1, participants
      adapted to either the typical "element motion" (ISI = 50 ms) or the typical
      "group motion" (ISI = 200 ms). In Experiments 2 and 3, participants adapted to a
      time interval of 50 or 200 ms through observing a series of two paired blinking
      discs at the center of the screen (Experiment 2) or hearing a sequence of two
      paired beeps (with pitch 1000 Hz). In Experiment 4, participants adapted to
      sequences of paired beeps with either low pitches (500 Hz) or high pitches (5000
      Hz). After adaptation in each trial, participants were presented with a Ternus
      probe in which the ISI between the two frames was equal to the transitional
      threshold of the two types of motions, as determined by a pretest. Results showed
      that adapting to the short time interval in all the situations led to more
      reports of "group motion" in the subsequent Ternus probes; adapting to the long
      time interval, however, caused no aftereffect for visual adaptation but
      significantly more reports of group motion for auditory adaptation. These
      findings, suggesting amodal representation for sub-second timing across
      modalities, are interpreted in the framework of temporal pacemaker model.

PMID- 23133409
TI  - The endocannabinoid system: a key modulator of emotions and cognition.

PMID- 23133410
TI  - Whisker encoding of mechanical events during active tactile exploration.
AB  - Rats use their whiskers to extract a wealth of information about their immediate
      environment, such as the shape, position or texture of an object. The information
      is conveyed to mechanoreceptors located within the whisker follicle in the form
      of a sequence of whisker deflections induced by the whisker/object contact
      interaction. How the whiskers filter and shape the mechanical information and
      effectively participate in the coding of tactile features remains an open
      question to date. In the present article, a biomechanical model was developed
      that provides predictions of the whisker dynamics during active tactile
      exploration, amenable to quantitative experimental comparison. This model is
      based on a decomposition of the whisker profile into a slow, quasi-static
      sequence and rapid resonant small-scale vibrations. It was applied to the typical
      situation of a rat actively whisking across a solid object. Having derived the
      quasi-static sequence of whisker deformation, the resonant properties of the
      whisker were analyzed, taking into account the boundary conditions imposed by the
      whisker/surface contact. We then focused on two elementary mechanical events that
      are expected to trigger significant neural responses, namely (1) the
      whisker/object first contact and (2) the whisker detachment from the object. Both
      events were found to trigger a deflection wave propagating upward to the
      mystacial pad at constant velocity of ~3-5 m/s. This yielded a characteristic
      mechanical signature at the whisker base, in the form of a large peak of negative
      curvature occurring ~4 ms after the event has been triggered. The dependence in
      amplitude and lag of this mechanical signal with the main contextual parameters
      (such as radial or angular distance) was investigated. The model was validated
      experimentally by comparing its predictions to high-speed video recordings of
      shock-induced whisker deflections performed on anesthetized rats. The
      consequences of these results on possible tactile encoding schemes are briefly
      discussed.

PMID- 23133411
TI  - Randomized controlled trial of mindfulness-based stress reduction versus aerobic
      exercise: effects on the self-referential brain network in social anxiety
      disorder.
AB  - BACKGROUND: Social anxiety disorder (SAD) is characterized by distorted self
      views. The goal of this study was to examine whether mindfulness-based stress
      reduction (MBSR) alters behavioral and brain measures of negative and positive
      self-views. METHODS: Fifty-six adult patients with generalized SAD were randomly
      assigned to MBSR or a comparison aerobic exercise (AE) program. A self
      referential encoding task was administered at baseline and post-intervention to
      examine changes in behavioral and neural responses in the self-referential brain
      network during functional magnetic resonance imaging. Patients were cued to
      decide whether positive and negative social trait adjectives were self
      descriptive or in upper case font. RESULTS: Behaviorally, compared to AE, MBSR
      produced greater decreases in negative self-views, and equivalent increases in
      positive self-views. Neurally, during negative self versus case, compared to AE,
      MBSR led to increased brain responses in the posterior cingulate cortex (PCC).
      There were no differential changes for positive self versus case. Secondary
      analyses showed that changes in endorsement of negative and positive self-views
      were associated with decreased social anxiety symptom severity for MBSR, but not
      AE. Additionally, MBSR-related increases in dorsomedial prefrontal cortex (DMPFC)
      activity during negative self-view versus case were associated with decreased
      social anxiety related disability and increased mindfulness. Analysis of neural
      temporal dynamics revealed MBSR-related changes in the timing of neural responses
      in the DMPFC and PCC for negative self-view versus case. CONCLUSION: These
      findings suggest that MBSR attenuates maladaptive habitual self-views by
      facilitating automatic (i.e., uninstructed) recruitment of cognitive and
      attention regulation neural networks. This highlights potentially important links
      between self-referential and cognitive-attention regulation systems and suggests
      that MBSR may enhance more adaptive social self-referential processes in patients
      with SAD.

PMID- 23133412
TI  - Once upon a time there was complex numerical estimation.

PMID- 23133413
TI  - Fully exploratory network independent component analysis of the 1000 functional
      connectomes database.
AB  - The 1000 Functional Connectomes Project is a collection of resting-state fMRI
      datasets from more than 1000 subjects acquired in more than 30 independent
      studies from around the globe. This large, heterogeneous sample of resting-state
      data offers the unique opportunity to study the consistencies of resting-state
      networks at both subject and study level. In extension to the seminal paper by
      Biswal et al. (2010), where a repeated temporal concatenation group independent
      component analysis (ICA) approach on reduced subsets (using 20 as a pre-specified
      number of components) was used due to computational resource limitations, we
      herein apply Fully Exploratory Network ICA (FENICA) to 1000 single-subject
      independent component analyses. This, along with the possibility of using
      datasets of different lengths without truncation, enabled us to benefit from the
      full dataset available, thereby obtaining 16 networks consistent over the whole
      group of 1000 subjects. Furthermore, we demonstrated that the most consistent
      among these networks at both subject and study level matched networks most often
      reported in the literature, and found additional components emerging in
      prefrontal and parietal areas. Finally, we identified the influence of scan
      duration on the number of components as a source of heterogeneity between
      studies.

PMID- 23133414
TI  - What is value-accumulated reward or evidence?
AB  - Why are you reading this abstract? In some sense, your answer will cast the
      exercise as valuable-but what is value? In what follows, we suggest that value is
      evidence or, more exactly, log Bayesian evidence. This implies that a sufficient
      explanation for valuable behavior is the accumulation of evidence for internal
      models of our world. This contrasts with normative models of optimal control and
      reinforcement learning, which assume the existence of a value function that
      explains behavior, where (somewhat tautologically) behavior maximizes value. In
      this paper, we consider an alternative formulation-active inference-that replaces
      policies in normative models with prior beliefs about the (future) states agents
      should occupy. This enables optimal behavior to be cast purely in terms of
      inference: where agents sample their sensorium to maximize the evidence for their
      generative model of hidden states in the world, and minimize their uncertainty
      about those states. Crucially, this formulation resolves the tautology inherent
      in normative models and allows one to consider how prior beliefs are themselves
      optimized in a hierarchical setting. We illustrate these points by showing that
      any optimal policy can be specified with prior beliefs in the context of Bayesian
      inference. We then show how these prior beliefs are themselves prescribed by an
      imperative to minimize uncertainty. This formulation explains the saccadic eye
      movements required to read this text and defines the value of the visual
      sensations you are soliciting.

PMID- 23133415
TI  - Inter-trial variability in sensory-evoked cortical hemodynamic responses: the
      role of the magnitude of pre-stimulus fluctuations.
AB  - Brain imaging techniques utilize hemodynamic changes that accompany brain
      activation. However, stimulus-evoked hemodynamic responses display considerable
      inter-trial variability and the sources of this variability are poorly
      understood. One of the sources of this response variation could be ongoing
      spontaneous hemodynamic fluctuations. We recently investigated this issue by
      measuring cortical hemodynamics in response to sensory stimuli in anesthetized
      rodents using 2-dimensional optical imaging spectroscopy. We suggested that
      sensory-evoked cortical hemodynamics displayed distinctive response
      characteristics and magnitudes depending on the phase of ongoing fluctuations at
      stimulus onset due to a linear superposition of evoked and ongoing hemodynamics
      (Saka et al., 2010). However, the previous analysis neglected to examine the
      possible influence of variability of the size of ongoing fluctuations.
      Consequently, data were further analyzed to examine whether the size of pre
      stimulus hemodynamic fluctuations also influenced the magnitude of subsequent
      stimulus-evoked responses. Indeed, in the case of all individual trials, a
      moderate correlation between the size of the pre-stimulus fluctuations and the
      magnitudes of the subsequent sensory-evoked responses were observed. However,
      different correlations between the size of the pre-stimulus fluctuations and
      magnitudes of the subsequent sensory-evoked cortical hemodynamic responses could
      be observed depending on their phase at stimulus onset. These analyses suggest
      that both the size and phase of pre-stimulus fluctuations in cortical
      hemodynamics contribute to inter-trial variability in sensory-evoked responses.

PMID- 23133416
TI  - Homer1 gene products orchestrate Ca(2+)-permeable AMPA receptor distribution and
      LTP expression.
AB  - We studied the role of Homer1 gene products on the presence of synaptic Ca(2+)
      permeable AMPA receptors (AMPARs) and long-term potentiation (LTP) generation in
      hippocampal CA1 pyramidal neurons, using mice either lacking all Homer1 isoforms
      (Homer1 KO) or overexpressing the immediate early gene (IEG) product Homer1a
      (H1aTG). We found that Homer1 KO caused a significant redistribution of the AMPAR
      subunit GluA2 from the dendritic compartment to the soma. Furthermore, deletion
      of Homer1 enhanced the AMPAR-mediated component of glutamatergic currents at
      Schaffer collateral synapses as demonstrated by increased AMPA/NMDA current
      ratios. Meanwhile, LTP generation appeared to be unaffected. Conversely,
      sustained overexpression of Homer1a strongly reduced AMPA/NMDA current ratios and
      polyamine sensitivity of synaptic AMPAR, indicating that the proportion of
      synaptic GluA2-containing AMPAR increased relative to WT. LTP maintenance was
      abolished in H1aTG. Notably, overexpression of Homer1a in Homer1 KO or GluA2 KO
      mice did not affect LTP expression, suggesting activity-dependent interaction
      between Homer1a and long Homer1 isoforms with GluA2-containing AMPAR. Thus,
      Homer1a is essential for the activity-dependent regulation of excitatory synaptic
      transmission.

PMID- 23133417
TI  - Warfarin pharmacogenetics: challenges and opportunities for clinical translation.

PMID- 23133418
TI  - Potential contribution of aromatase inhibition to the effects of nicotine and
      related compounds on the brain.
AB  - Cigarette smoking continues to be a major public health problem, and while
      smoking rates in men have shown some decrease over the last few decades, smoking
      rates among girls and young women are increasing. Practically all of the
      important aspects of cigarette smoking and many effects of nicotine are sexually
      dimorphic (reviewed by Pogun and Yararbas, 2009). Women become addicted more
      easily than men, while finding it harder to quit. Nicotine replacement appears to
      be less effective in women. This may be linked to the observation that women are
      more sensitive than men to non-nicotine cues or ingredients in cigarettes. The
      reasons for these sex differences are mostly unknown. Several lines of evidence
      suggest that many of the reported sex differences related to cigarette smoking
      may stem from the inhibitory effects of nicotine and other tobacco alkaloids on
      estrogen synthesis via the enzyme aromatase (cyp19a gene product). Aromatase is
      the last enzyme in estrogen biosynthesis, catalyzing the conversion of androgens
      to estrogens. This review provides a summary of experimental evidence supporting
      brain aromatase as a potential mediator and/or modulator of nicotine actions in
      the brain, contributing to sex differences in smoking behavior. Additional
      research on the interaction between tobacco smoke, nicotine, and aromatase may
      help devise new, sex specific methods for prevention and treatment of smoking
      addiction.

PMID- 23133419
TI  - Rapid effect of nicotine intake on neuroplasticity in non-smoking humans.
AB  - In various studies nicotine has shown to alter cognitive functions in non-smoking
      subjects. The physiological basis for these effects might be nicotine-generated
      modulation of cortical structure, excitability, and activity, as mainly described
      in animal experiments. In accordance, a recently conducted study demonstrated
      that application of nicotine for hours via nicotine patch in non-smoking humans
      alters the effects of neuroplasticity-inducing non-invasive brain stimulation
      techniques on cortical excitability. Specifically, nicotine abolished inhibitory
      plasticity independent from the focality of the stimulation protocol. While
      nicotine prevented also the establishment of non-focal facilitatory plasticity,
      focal synapse-specific facilitatory plasticity was enhanced. These results agree
      with a focusing effect of prolonged nicotine application on facilitatory
      plasticity. However, since nicotine induces rapid adaption processes of its
      receptors, this scenario might differ from the effect of nicotine in cigarette
      smoking. Thus in this study we aimed to gain further insight in the mechanism of
      nicotine on plasticity by exploring the effect of nicotine spray on non-focal and
      focal plasticity-inducing protocols in non-smoking subjects, a fast-acting agent
      better comparable to cigarette smoking. Focal, synapse-specific plasticity was
      induced by paired associative stimulation (PAS), while non-focal plasticity was
      elicited by transcranial direct current stimulation (tDCS). Forty eight non
      smokers received nicotine spray respectively placebo combined with one of the
      following protocols (anodal tDCS, cathodal tDCS, PAS-25, and PAS-10).
      Corticospinal excitability was monitored via motor-evoked potentials elicited by
      transcranial magnetic stimulation (TMS). Nicotine spray abolished facilitatory
      plasticity irrespective of focality and PAS-10-induced excitability diminution,
      while tDCS-derived excitability reduction was delayed and weakened. Nicotine
      spray had thus a clear effect on neuroplasticity in non-smoking subjects.
      However, the effects of nicotine spray differ clearly from those of prolonged
      nicotine application, which might be due to missing adaptive nicotinic receptor
      alterations. These results enhance our knowledge about the dynamic impact of
      nicotine on plasticity, which might be related to its heterogenous effect on
      cognition.

PMID- 23133420
TI  - Pharmacogenomic Diversity among Brazilians: Influence of Ancestry, Self-Reported
      Color, and Geographical Origin.
AB  - BY VIRTUE OF BEING THE PRODUCT OF THE GENETIC ADMIXTURE OF THREE ANCESTRAL ROOTS:
      Europeans, Africans, and Amerindians, the present-day Brazilian population
      displays very high levels of genomic diversity, which have important
      pharmacogenetic/-genomic (PGx) implications. Recognition of this fact has
      prompted the creation of the Brazilian Pharmacogenomics Network (Refargen), a
      nationwide consortium of research groups, with the mission to provide leadership
      in PGx research and education in Brazil, with a population heath impact. Here, we
      present original data and review published results from a Refargen comprehensive
      study of the distribution of PGx polymorphisms in a representative cohort of the
      Brazilian people, comprising 1,034 healthy, unrelated adults, self-identified as
      white, brown, or black, according to the Color categories adopted by the
      Brazilian Census. Multinomial log-linear regression analysis was applied to infer
      the statistical association between allele, genotype, and haplotype distributions
      among Brazilians (response variables) and self-reported Color, geographical
      region, and biogeographical ancestry (explanatory variables), whereas Wright's
      F(ST) statistics was used to assess the extent of PGx divergence among different
      strata of the Brazilian population. Major PGx implications of these findings are:
      first, extrapolation of data from relatively well-defined ethnic groups is
      clearly not applicable to the majority of Brazilians; second, the frequency
      distribution of polymorphisms in several pharmacogenes of clinical relevance
      (e.g., ABCB1, CYP3A5, CYP2C9, VKORC) varies continuously among Brazilians and is
      not captured by race/Color self-identification; third, the intrinsic
      heterogeneity of the Brazilian population must be acknowledged in the design and
      interpretation of PGx studies in order to avoid spurious conclusions based on
      improper matching of study cohorts.

PMID- 23133422
TI  - Molecular mechanisms of pancreatic stone formation in chronic pancreatitis.
AB  - Chronic pancreatitis (CP) is a progressive inflammatory disease in which the
      pancreatic secretory parenchyma is destroyed and replaced by fibrosis. The
      presence of intraductal pancreatic stone(s) is important for the diagnosis of CP;
      however, the precise molecular mechanisms of pancreatic stone formation in CP
      were left largely unknown. Cystic fibrosis transmembrane conductance regulator
      (CFTR) is a chloride channel expressed in the apical plasma membrane of
      pancreatic duct cells and plays a central role in [Formula: see text] secretion.
      In previous studies, we have found that CFTR is largely mislocalized to the
      cytoplasm of pancreatic duct cells in all forms of CP and corticosteroids
      normalizes the localization of CFTR to the proper apical membrane at least in
      autoimmune pancreatitis. From these observations, we could conclude that the
      mislocalization of CFTR is a cause of protein plug formation in CP, subsequently
      resulting in pancreatic stone formation. Considering our observation that the
      mislocalization of CFTR also occurs in alcoholic or idiopathic CP, it is very
      likely that these pathological conditions can also be treated by corticosteroids,
      thereby preventing pancreatic stone formation in these patients. Further studies
      are definitely required to clarify these fundamental issues.

PMID- 23133421
TI  - The dynamics of somatic exocytosis in monoaminergic neurons.
AB  - Some monoaminergic neurons can release neurotransmitters by exocytosis from their
      cell bodies. The amount of monoamine released by somatic exocytosis can be
      comparable to that released by synaptic exocytosis, though neither the underlying
      mechanisms nor the functional significance of somatic exocytosis are well
      understood. A detailed examination of these characteristics may provide new
      routes for therapeutic intervention in mood disorders, substance addiction, and
      neurodegenerative diseases. The relatively large size of the cell body provides a
      unique opportunity to understand the mechanism of this mode of neuronal
      exocytosis in microscopic detail. Here we used three photon and total internal
      reflection fluorescence microscopy to focus on the dynamics of the pre-exocytotic
      events and explore the nature of somatic vesicle storage, transport, and docking
      at the membrane of serotonergic neurons from raphe nuclei of the rat brain. We
      find that the vesicles (or unresolved vesicular clusters) are quiescent (mean
      square displacement, MSD ~0.04 MUm(2)/s) before depolarization, and they move
      minimally (<1 MUm) from their locations over a time-scale of minutes. However,
      within minutes of depolarization, the vesicles become more dynamic (MSD ~0.3
      MUm(2)/s), and display larger range (several MUm) motions, though without any
      clear directionality. Docking and subsequent exocytosis at the membrane happen at
      a timescale (~25 ms) that is slower than most synaptic exocytosis processes, but
      faster than almost all somatic exocytosis processes observed in endocrine cells.
      We conclude that, (A) depolarization causes de-tethering of the neurotransmitter
      vesicles from their storage locations, and this constitutes a critical event in
      somatic exocytosis; (B) their subsequent transport kinetics can be described by a
      process of constrained diffusion, and (C) the pre-exocytosis kinetics at the
      membrane is faster than most other somatic exocytosis processes reported so far.

PMID- 23133423
TI  - Rapid genetic algorithm optimization of a mouse computational model: benefits for
      anthropomorphization of neonatal mouse cardiomyocytes.
AB  - While the mouse presents an invaluable experimental model organism in biology,
      its usefulness in cardiac arrhythmia research is limited in some aspects due to
      major electrophysiological differences between murine and human action potentials
      (APs). As previously described, these species-specific traits can be partly
      overcome by application of a cell-type transforming clamp (CTC) to
      anthropomorphize the murine cardiac AP. CTC is a hybrid experimental
      computational dynamic clamp technique, in which a computationally calculated time
      dependent current is inserted into a cell in real-time, to compensate for the
      differences between sarcolemmal currents of that cell (e.g., murine) and the
      desired species (e.g., human). For effective CTC performance, mismatch between
      the measured cell and a mathematical model used to mimic the measured AP must be
      minimal. We have developed a genetic algorithm (GA) approach that rapidly tunes a
      mathematical model to reproduce the AP of the murine cardiac myocyte under study.
      Compared to a prior implementation that used a template-based model selection
      approach, we show that GA optimization to a cell-specific model results in a much
      better recapitulation of the desired AP morphology with CTC. This improvement was
      more pronounced when anthropomorphizing neonatal mouse cardiomyocytes to human
      like APs than to guinea pig APs. CTC may be useful for a wide range of
      applications, from screening effects of pharmaceutical compounds on ion channel
      activity, to exploring variations in the mouse or human genome. Rapid GA
      optimization of a cell-specific mathematical model improves CTC performance and
      may therefore expand the applicability and usage of the CTC technique.

PMID- 23133424
TI  - Networking of psychophysics, psychology, and neurophysiology.

PMID- 23133425
TI  - Editorial: engineering approaches to study cardiovascular physiology: modeling,
      estimation, and signal processing.

PMID- 23133426
TI  - Suppression by gamma-Hydroxybutyric Acid of "Alcohol Deprivation Effect" in Rats:
      Preclinical Evidence of its anti-Relapse Properties.
AB  - gamma-Hydroxybutyric acid (GHB) reduces (a) alcohol intake and alcohol
      motivational properties in alcohol-preferring rats and (b) alcohol drinking and
      craving for alcohol in human alcoholics. The present study was designed to extend
      to relapse-like drinking the capacity of GHB to suppress different alcohol
      related behaviors in alcohol-preferring rats. The "alcohol deprivation effect,"
      defined as the temporary increase in alcohol intake occurring in laboratory
      animals after a period of alcohol deprivation, was used as model of alcohol
      relapse. Acute administration of non-sedative doses of GHB (0, 100, 200, and 300
      mg/kg, i.p.) resulted in the complete suppression of the extra-amount of alcohol
      consumed by Sardinian alcohol-preferring rats during the first hour of re-access
      to alcohol after a 14-day period of deprivation. These data demonstrate that GHB
      suppressed relapse-like drinking in a rat model of excessive alcohol consumption.

PMID- 23133427
TI  - Neurological evidence linguistic processes precede perceptual simulation in
      conceptual processing.
AB  - There is increasing evidence from response time experiments that language
      statistics and perceptual simulations both play a role in conceptual processing.
      In an EEG experiment we compared neural activity in cortical regions commonly
      associated with linguistic processing and visual perceptual processing to
      determine to what extent symbolic and embodied accounts of cognition applied.
      Participants were asked to determine the semantic relationship of word pairs
      (e.g., sky - ground) or to determine their iconic relationship (i.e., if the
      presentation of the pair matched their expected physical relationship). A
      linguistic bias was found toward the semantic judgment task and a perceptual bias
      was found toward the iconicity judgment task. More importantly, conceptual
      processing involved activation in brain regions associated with both linguistic
      and perceptual processes. When comparing the relative activation of linguistic
      cortical regions with perceptual cortical regions, the effect sizes for
      linguistic cortical regions were larger than those for the perceptual cortical
      regions early in a trial with the reverse being true later in a trial. These
      results map upon findings from other experimental literature and provide further
      evidence that processing of concept words relies both on language statistics and
      on perceptual simulations, whereby linguistic processes precede perceptual
      simulation processes.

PMID- 23133428
TI  - Language Effects in Trilinguals: An ERP Study.
AB  - Event-related potentials were recorded during the visual presentation of words in
      the three languages of French-English-Spanish trilinguals. Participants monitored
      a mixed list of unrelated non-cognate words in the three languages while
      performing a semantic categorization task. Words in L1 generated earlier N400
      peak amplitudes than both L2 and L3 words, which peaked together. On the other
      hand, L2 and L3 words did differ significantly in terms of N400 amplitude, with
      L3 words generating greater mean amplitudes compared with L2 words. We interpret
      the effects of peak N400 latency as reflecting the special status of the L1
      relative to later acquired languages, rather than proficiency in that language
      per se. On the other hand, the mean amplitude difference between L2 and L3 is
      thought to reflect different levels of fluency in these two languages.

PMID- 23133429
TI  - What is to be Done? Why Reward is Difficult to Do Without.

PMID- 23133430
TI  - Children using cochlear implants capitalize on acoustical hearing for music
      perception.
AB  - Cochlear implants (CIs) electrically stimulate the auditory nerve providing
      children who are deaf with access to speech and music. Because of device
      limitations, it was hypothesized that children using CIs develop abnormal
      perception of musical cues. Perception of pitch and rhythm as well as memory for
      music was measured by the children's version of the Montreal Battery of
      Evaluation of Amusia (MBEA) in 23 unilateral CI users and 22 age-matched children
      with normal hearing. Children with CIs were less accurate than their normal
      hearing peers (p < 0.05). CI users were best able to discern rhythm changes (p <
      0.01) and to remember musical pieces (p < 0.01). Contrary to expectations,
      abilities to hear cues in music improved as the age at implantation increased (p
      < 0.01). Because the children implanted at older ages also had better low
      frequency hearing prior to cochlear implantation and were able to use this
      hearing by wearing hearing aids. Access to early acoustical hearing in the lower
      frequency ranges appears to establish a base for music perception, which can be
      accessed with later electrical CI hearing.

PMID- 23133431
TI  - Attentional focus and performance anxiety: effects on simulated race-driving
      performance and heart rate variability.
AB  - Previous studies have demonstrated that an external focus can enhance motor
      learning compared to an internal focus. The benefits of adopting an external
      focus are attributed to the use of less effortful automatic control processes,
      while an internal focus relies upon more effort-intensive consciously controlled
      processes. The aim of this study was to compare the effectiveness of a distal
      external focus with an internal focus in the acquisition of a simulated driving
      task and subsequent performance in a competitive condition designed to increase
      state anxiety. To provide further evidence for the automatic nature of externally
      controlled movements, the study included heart rate variability (HRV) as an index
      of mental effort. Sixteen participants completed eight blocks of four laps in
      either a distal external or internal focus condition, followed by two blocks of
      four laps in the competitive condition. During acquisition, the performance of
      both groups improved; however, the distal external focus group outperformed the
      internal focus group. The poorer performance of the internal focus group was
      accompanied by a larger reduction in HRV, indicating a greater investment of
      mental effort. In the competition condition, state anxiety increased, and for
      both groups, performance improved as a function of the increased anxiety.
      Increased heart rate and self-reported mental effort accompanied the performance
      improvement. The distal external focus group also outperformed the internal focus
      group across both neutral and competitive conditions and this more effective
      performance was again associated with lower levels of HRV. Overall, the results
      offer support for the suggestion that an external focus promotes a more automatic
      mode of functioning. In the competitive condition, both foci enhanced performance
      and while the improved performance may have been achieved at the expense of
      greater compensatory mental effort, this was not reflected in HRV scores.

PMID- 23133432
TI  - "Cutaneous rabbit" hops toward a light: unimodal and cross-modal causality on the
      skin.
AB  - Our somatosensory system deals with not only spatial but also temporal
      imprecision, resulting in characteristic spatiotemporal illusions. Repeated rapid
      stimulation at the wrist, then near the elbow, can create the illusion of touch
      at intervening locations along the arm (as if a rabbit is hopping along the arm).
      This is known as the "cutaneous rabbit effect" (CRE). Previous studies have
      suggested that the CRE involves not only an intrinsic somatotopic representation
      but also the representation of an extended body schema that includes causality or
      animacy perception upon the skin. On the other hand, unlike other multi-modal
      causality couplings, it is possible that the CRE is not affected by concurrent
      auditory temporal information. The present study examined the effect of a simple
      visual flash on the CRE, which has both temporal and spatial information. Here,
      stronger cross-modal causality or correspondence could be provided. We presented
      three successive tactile stimuli on the inside of a participant's left arm.
      Stimuli were presented on the wrist, elbow, and midway between the two. Results
      from our five experimental manipulations suggest that a one-shot flash enhances
      or attenuates the CRE depending on its congruency with cutaneous rabbit
      saltation. Our results reflect that (1) our brain interprets successive stimuli
      on the skin as motion in terms of time and space (unimodal causality) and that
      (2) the concurrent signals from other modalities provide clues for creating
      unified representations of this external motion (multi-modal causality) as to the
      extent that "spatiotemporal" synchronicity among modalities is provided.

PMID- 23133433
TI  - An Experimental Decision-Making Paradigm to Distinguish Guilt and Regret and
      Their Self-Regulating Function via Loss Averse Choice Behavior.
AB  - Both guilt and regret typically result from counterfactual evaluations of
      personal choices that caused a negative outcome and are thought to regulate human
      decisions by people's motivation to avoid these emotions. Despite these
      similarities, studies asking people to describe typical situations of guilt and
      regret identified the social dimension as a fundamental distinguishing factor,
      showing that guilt but not regret specifically occurs for choices in
      interpersonal (social) contexts. However, an experimental paradigm to investigate
      this distinction systematically by inducing emotions of guilt and regret online
      is still missing. Here, extending existing procedures, we introduce such a
      paradigm, in which participants choose in each trial between two lotteries, with
      the outcome of the chosen lottery (gain or loss) being either assigned to
      themselves (intrapersonal trials) or to another person (interpersonal trials).
      After results of both the chosen and the unchosen lottery were shown, subjects
      rated how they felt about the outcome, including ratings of guilt and regret.
      Trait Guilt (TG) was determined for all participants in order to take their
      general inclination to experience guilt into account. Results confirmed that
      guilt but not regret specifically occurred in an interpersonal context.
      Percentages of loss averse choices (choosing the lottery with the lower possible
      monetary loss) were determined as indicators of regulation via guilt and regret
      avoidance. High TG scorers generally made more loss averse choices than low TG
      scorers, while trial-by-trial analyses showed that low TG scorers used their
      feelings of guilt more specifically to avoid the same emotional experience in
      subsequent choices. Our results confirm the social dimension as the critical
      factor distinguishing guilt from regret and identify TG as an important moderator
      determining the way in which guilt vs. regret can regulate their own occurrence
      by influencing choice strategies.

PMID- 23133434
TI  - Motivational Mechanisms and Outcome Expectancies Underlying the Approach Bias
      toward Addictive Substances.
AB  - Human behavior can be paradoxical, in that actions can be initiated that are
      seemingly incongruent with an individual's explicit desires. This is most
      commonly observed in drug addiction, where maladaptive behavior (i.e., drug
      seeking) appears to be compulsive, continuing at great personal cost. Approach
      biases toward addictive substances have been correlated with actual drug-use in a
      number of studies, suggesting that this measure can, in some cases, index
      everyday maladaptive tendencies. At present it is unclear whether this bias to
      drug cues is a Pavlovian conditioned approach response, a habitual response, the
      result of a Pavlovian-instrumental transfer process, or a goal-directed action in
      the sense that expectancy of the rewarding effects of drugs controls approach. We
      consider this question by combining the theoretical framework of associative
      learning with the available evidence from approach bias research. Although
      research investigating the relative contributions of these mechanisms to the
      approach bias is to date relatively limited, we review existing studies and also
      outline avenues for future research.

PMID- 23133435
TI  - An Active Inference view of cognitive control.

PMID- 23133436
TI  - Hypothesis: Cryptochromes and Brown Fat are Essential for Adaptation and Affect
      Mood and Mood-Related Behaviors.
AB  - Solar radiation and ambient temperature have acted as selective physical forces
      among populations and thereby guided species distributions in the globe.
      Circadian clocks are universal and evolve when subjected to selection, and their
      properties contribute to variations in fitness within specific environments.
      Concerning humans, as compared to the remaining, the "evening owls" have a
      greater deviation from the 24 h cycle, are under a greater pressure to circadian
      desynchrony and more prone to a cluster of health hazards with the increased
      mortality. Because of their position in the hierarchy and repressive actions,
      cryptochromes are the key components of the feedback loops on which circadian
      clocks are built. Based on the evidence a new hypothesis is formulated in which
      brown adipocytes with their cryptochromes are responsive to a broad range of
      physical stimuli from the habitat and through their activity ensure adaptation of
      the individual. The over-activated brown adipose tissue with deficient
      cryptochromes might induce disrupted thermoregulation and circadian desynchrony,
      and thereby contribute to lowered mood and pronounced depressive behaviors.

PMID- 23133437
TI  - Genomic and epigenomic alterations in prostate cancer.
AB  - Prostate cancer (PC) is the second most frequently diagnosed cancer and the
      second leading cause of cancer deaths in man. The treatment of localized PC
      includes surgery or radiation therapy. In case of relapse after a definitive
      treatment or in patients with locally advanced or metastatic disease, the
      standard treatment includes the androgen-deprivation therapy (ADT). By reducing
      the levels of testosterone and dihydrotestosterone under the castration
      threshold, the ADT acts on the androgen receptor (AR), even if indirectly. The
      effects of the ADT are usually temporary and nearly all patients, initially
      sensitive to the androgen ablation therapy, have a disease progression after an
      18-24 months medium term. This is probably due to the selection of the cancer
      cell clones and to their acquisition of critical somatic genome and epigenomic
      changes. This review aims to provide an overview about the genetic and epigenetic
      alterations having a crucial role in the carcinogenesis and in the disease
      progression toward the castration resistant PC. We focused on the role of the AR,
      on its signaling cascade and on the clinical implications that the knowledge of
      these aspects would have on hormonal therapy, on its failure and its toxicity.

PMID- 23133439
TI  - In silico 3D structure analysis accelerates the solution of a real viral
      structure and antibodies docking mechanism.
AB  - Norwalk virus (NoV) is responsible for most outbreaks of non-bacterial
      gastroenteritis. NoV is genetically diverse and show antigenically variable.
      Recently, we produced a monoclonal antibody called 5B-18 that reacts broadly with
      NoV genogroup II (GII). We suspected the 5B-18 binds to a conformational epitope
      on 3D structure of virion. X-ray crystallography showed us that 5B-18 binds to
      NoV at the P domain, which protrudes from the capsid surface of the virion.
      However, there seems to be no space that would allow the IgG to approach the
      virion. To solve this problem, we used cryo-electron microscopy to examine NoV
      GII virus-like particles (VLPs). The P domain rises up higher in NoV GII than in
      NoV GI, and it seems to form an outer layer around the virion. Finally, using in
      silico modeling we found the 5B-18 Fab arms and NoV P region are quite flexible,
      so that 5B-18 can bind the NoV virion from bottom of P domain. This study
      demonstrates the shortcomings of studying biological phenomenon by only one
      technique. Each method has limitations. Multiple methods and modeling in silico
      are the keys to solving structural problems.

PMID- 23133438
TI  - Coordination of hypoxia adaptation and iron homeostasis in human pathogenic
      fungi.
AB  - In mammals, hypoxia causes facilitated erythropoiesis that requires increased
      iron availability with established links between oxygen and iron in regulation of
      the transcription factor hypoxia-inducible factor. Therefore, cellular responses
      to hypoxia and iron starvation are linked in mammals and are host conditions that
      pathogens encounter during infection. In human pathogenic fungi, molecular
      mechanisms underlying hypoxia adaptation and iron homeostasis have been
      investigated. However, the interconnected regulation of hypoxia adaptation and
      iron homeostasis remains to be fully elucidated. This review discusses the
      potential transcriptional regulatory links between hypoxia adaptation and iron
      homeostasis in human pathogenic fungi. Transcriptome analyses demonstrate that
      core regulators of hypoxia adaptation and iron homeostasis are involved in
      regulation of several common genes responsible for iron acquisition and
      ergosterol biosynthesis. Importantly, iron starvation increases susceptibility of
      fungal cells to antifungal drugs and decreased levels of ergosterol, while key
      hypoxia regulators are also involved in responses to antifungal drugs and
      mediating ergosterol levels. We suggest that pathogenic fungi have developed a
      coordinated regulatory system in response to hypoxia and iron starvation through
      (i) regulation of expression of hypoxia-responsive and iron-responsive genes via
      cross-linked key regulators, and/or (ii) regulation of factors involved in
      ergosterol biosynthesis. Thus, both oxygen and iron availability are intimately
      tied with fungal virulence and responses to existing therapeutics and further
      elucidation of their interrelationship should have significant clinical
      implications.

PMID- 23133440
TI  - Regulation and use of the extracellular matrix by Trypanosoma cruzi during early
      infection.
AB  - Chagas disease, which was once thought to be confined to endemic regions of Latin
      America, has now gone global becoming a new worldwide challenge. For more than a
      century since its discovery, it has remained neglected with no effective drugs or
      vaccines. The mechanisms by which Trypanosoma cruzi regulates and uses the
      extracellular matrix (ECM) to invade cells and cause disease are just beginning
      to be understood. Here we critically review and discuss the regulation of the ECM
      interactome by T. cruzi, the use of the ECM by T. cruzi and analyze the molecular
      ECM/T. cruzi interphase during the early process of infection. It has been shown
      that invasive trypomastigote forms of T. cruzi use and modulate components of the
      ECM during the initial process of infection. Infective trypomastigotes up
      regulate the expression of laminin gamma-1 (LAMC1) and thrombospondin (THBS1) to
      facilitate the recruitment of trypomastigotes to enhance cellular infection.
      Silencing the expression of LAMC1 and THBS1 by stable RNAi dramatically reduces
      trypanosome infection. T. cruzi gp83, a ligand that mediates the attachment of
      trypanosomes to cells to initiate infection, up-regulates LAMC1 expression to
      enhance cellular infection. Infective trypomastigotes use Tc85 to interact with
      laminin, p45 mucin to interact with LAMC1 through galectin-3 (LGALS3), a human
      lectin, and calreticulin (TcCRT) to interact with TSB1 to enhance cellular
      infection. Silencing the expression of LGALS3 also reduces cellular infection.
      Despite the role of the ECM in T. cruzi infection, almost nothing is known about
      the ECM interactome networks operating in the process of T. cruzi infection and
      its ligands. Here, we present the first elucidation of the human ECM interactome
      network regulated by T. cruzi and its gp83 ligand that facilitates cellular
      infection. The elucidation of the human ECM interactome regulated by T. cruzi and
      the dissection of the molecular ECM/T. cruzi interphase using systems biology
      approaches are not only critically important for the understanding of the
      molecular pathogenesis of T. cruzi infection but also for developing novel
      approaches of intervention in Chagas disease.

PMID- 23133441
TI  - ABCB1 4036A>G and 1236C>T Polymorphisms Affect Plasma Efavirenz Levels in South
      African HIV/AIDS Patients.
AB  - The ABCB1 gene encodes P-glycoprotein, an ATP-dependent drug efflux pump, which
      is responsible for drug transport across extra- and intra-cellular membranes. The
      variability in the expression of ABCB1 may contribute to variable plasma
      efavirenz concentration which results in variability in the levels of suppression
      of the human immunodeficiency syndrome virus (HIV). The aim of the study was to
      evaluate the role of polymorphisms in ABCB1 gene on plasma efavirenz levels and
      treatment response in the form of change in viral load and CD-4 cell count in
      HIV/AIDS patients receiving efavirenz-containing highly active antiretroviral
      treatment regimens. Two hundred and eighty-two HIV-infected patients were
      recruited from Themba Lethu Clinic in Johannesburg and plasma efavirenz drug
      concentration levels were measured using LC-MS/MS. SNaPshot was used to genotype
      five known ABCB1 single nucleotide polymorphisms (SNPs). Genotype-phenotype
      correlations were computed. The ABCB1 4036A/G and 4036G/G genotypes were
      significantly associated with low plasma efavirenz concentrations (P = 0.0236),
      while the ABCB1 1236C/T and 1236T/T genotypes were associated with high efavirenz
      concentrations (P = 0.0282). A haplotype ABCB1 T-G-T-A is reported that is
      associated with significantly increased plasma efavirenz levels. This is the
      first report on 61A>G, 2677G>T/A, and 4036A>G SNPs in the South African
      population. ABCB1 plays a role in determining the plasma concentrations of
      efavirenz and should be taken into account in future design of assays for
      genotype-based dosing of efavirenz-containing regimens.

PMID- 23133442
TI  - Epigenetic regulation of human embryonic stem cells.
AB  - Recently, there has been tremendous progress in characterizing the
      transcriptional network regulating human embryonic stem cells (hESCs; MacArthur
      etal., 2009; Loh etal., 2011), including those signaling events mediated by Oct4,
      Nanog, and Sox2. There is growing interest in the epigenetic machinery involved
      in hESC self-renewal and differentiation. In general, epigenetic regulation
      includes chromatin reorganization, DNA modification, and histone modification,
      which are not directly related to alterations in DNA sequences. Various protein
      complexes, including Polycomb, trithorax, nucleosome remodeling deacetylase,
      SWI/SNF, and Oct4, have been shown to play critical roles in epigenetic control
      of hESC physiology. Hence, we will formally review recent advances in unraveling
      the multifaceted role of epigenetic regulation in hESC self-renewal and induced
      differentiation, particularly with respect to chromatin remodeling and DNA
      methylation events. Elucidating the molecular mechanisms underlying the
      maintenance/differentiation of hESCs and reprogramming of somatic cells will
      greatly strengthen our capacity to generate various types of cells to treat human
      diseases.

PMID- 23133443
TI  - Cardiovascular disease risk in the offspring of diabetic women: the impact of the
      intrauterine environment.
AB  - The incidence of gestational diabetes is increasing worldwide, exposing large
      numbers of infants to hyperglycaemia whilst in utero. This exposure may have a
      long-term negative impact on the cardiovascular health of the offspring. Novel
      methods to assess cardiovascular status in the neonatal period are now available
      including measuring arterial intima-media thickness and retinal photography.
      These measures will allow researchers to assess the relative impact of
      intrauterine exposures, distinguishing these from genetic or postnatal
      environmental factors. Understanding the long-term impact of the intrauterine
      environment should allow the development of more effective health policy and
      interventions to decrease the future burden of cardiovascular disease. Initiating
      disease prevention aimed at the developing fetus during the antenatal period may
      optimise community health outcomes.

PMID- 23133444
TI  - Genetic variation in CYP17A1 is associated with arterial stiffness in diabetic
      subjects.
AB  - Hypertension and arterial stiffness are associated with an increasing risk of
      diabetes and cardiovascular diseases. This study aimed to identify genetic
      variants affecting hypertension and arterial stiffness in diabetic subjects and
      to compare genetic associations with hypertension between prediabetic and
      diabetic subjects. A total of 1,069 participants (326 prediabetic and 743
      diabetic subjects) were assessed to determine the genetic variants affecting
      hypertension by analyzing 52 SNPs previously reported to be associated with
      hypertension. Moreover, the SNPs were tested for association with hemodynamic
      parameters related to hypertension. Out of the 52 SNPs analyzed, four SNPs
      including rs5326 (DRD1), rs1004467 (CYP17A1), rs2960306 (GRK4), and rs11191548
      (near NT5C2) in diabetic subjects and rs1530440 (C10orf107) in prediabetic
      subjects showed a modest association with hypertension (P = 0.0265, 0.0020,
      0.0066, 0.0078, and 0.0015, resp; all were insignificant after Bonferroni
      correction). Of these SNPs, rs1004467 in CYP17A1 was significantly associated
      with augmentation index in diabetic subjects who were not taking antihypertensive
      medication (P = 0.0001; corrected P = 0.006) but not in diabetic subjects
      receiving antihypertensive medication. This finding suggests that certain genetic
      variations found in diabetic subjects may confer arterial stiffness and the
      development of hypertension and also be affected by antihypertensive medication.

PMID- 23133445
TI  - Bull's-Eye and Nontarget Skin Lesions of Lyme Disease: An Internet Survey of
      Identification of Erythema Migrans.
AB  - Introduction. Lyme disease is an emerging worldwide infectious disease with major
      foci of endemicity in North America and regions of temperate Eurasia. The
      erythema migrans rash associated with early infection is found in approximately
      80% of patients and can have a range of appearances including the classic target
      bull's-eye lesion and nontarget appearing lesions. Methods. A survey was designed
      to assess the ability of the general public to distinguish various appearances of
      erythema migrans from non-Lyme rashes. Participants were solicited from
      individuals who visited an educational website about Lyme disease. Results. Of
      3,104 people who accessed a rash identification survey, 72.7% of participants
      correctly identified the classic target erythema migrans commonly associated with
      Lyme disease. A mean of 20.5% of participants was able to correctly identify the
      four nonclassic erythema migrans. 24.2% of participants incorrectly identified a
      tick bite reaction in the skin as erythema migrans. Conclusions. Participants
      were most familiar with the classic target erythema migrans of Lyme disease but
      were unlikely to correctly identify the nonclassic erythema migrans. These
      results identify an opportunity for educational intervention to improve early
      recognition of Lyme disease and to increase the patient's appropriate use of
      medical services for early Lyme disease diagnosis.

PMID- 23133446
TI  - Interdisciplinary management of cystic neoplasms of the pancreas.
AB  - Cystic neoplasms of the pancreas are increasingly recognized due to the frequent
      use of abdominal imaging. It is reported that up to 20% of abdominal cross
      sectional scans identify incidental asymptomatic pancreatic cysts. Proper
      characterization of pancreatic cystic neoplasms is important not only to
      recognize premalignant lesions that will require surgical resection, but also to
      allow nonoperative management of many cystic lesions that will not require
      resection with its inherent morbidity. Though reliable biomarkers are lacking, a
      wide spectrum of diagnostic modalities are available to evaluate pancreatic
      cystic neoplasms, including radiologic, endoscopic, laboratory, and pathologic
      analysis. An interdisciplinary approach to management of these lesions which
      incorporates recent, specialty-specific advances in the medical literature is
      herein suggested.

PMID- 23133447
TI  - Effect of gastrointestinal surgical manipulation on metabolic syndrome: a focus
      on metabolic surgery.
AB  - Metabolic syndrome is strictly associated with morbid obesity and leads to an
      increased risk of cardiovascular diseases and related mortality. Bariatric
      surgery is considered an effective option for the management of these patients.
      We searched MEDLINE, Current Contents, and the Cochrane Library for papers
      published on bariatric surgery outcomes in English from 1 January 1990 to 20 July
      2012. We reported the effect of gastrointestinal manipulation on metabolic
      syndrome after bariatric surgery. Bariatric surgery determines an important
      resolution rate of major obesity-related comorbidities. Roux-en-Y gastric bypass
      and biliopancreatic diversion appear to be more effective than adjustable gastric
      banding in terms of weight loss and comorbidities resolution. However, the
      results obtained in terms of weight loss and resolution of comorbidities after a
      "new bariatric procedure" (sleeve gastrectomy) encouraged and stimulated the
      diffusion of this operation.

PMID- 23133448
TI  - Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy: insights into
      genotype-phenotype correlation.
AB  - Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a rare
      autosomal recessive disease, caused by mutations of a single gene named
      autoimmune regulator gene (AIRE) which results in a failure of T cell tolerance
      within the thymus. Chronic mucocutaneous candidiasis, chronic hypoparathyroidism,
      and Addison's disease are the hallmarks of the syndrome. APECED is also
      characterized by several autoimmune endocrine and nonendocrine manifestations,
      and the phenotype is often complex. Moreover, even though APECED is a monogenic
      disease, its clinical picture is generally dominated by a wide heterogeneity both
      in the severity and in the number of components even among siblings with the same
      AIRE genotype. The variability of its clinical expression implies that diagnosis
      can be challenging, and a considerable delay often occurs between the appearance
      of symptoms and the diagnosis. Since a prompt diagnosis is essential to prevent
      severe complications, clinicians should be aware of all symptoms and signs of
      suspicion. The aim of this paper is to give an overview on the clinical
      presentation and diagnostic criteria of APECED and to focus on current knowledge
      on genotype-phenotype correlation.

PMID- 23133449
TI  - Radiofrequency ablation of thyroid nodules: basic principles and clinical
      application.
AB  - Radiofrequency (RF) ablation has been gaining popularity as a minimally invasive
      treatment for benign thyroid nodules regardless of the extent of the solid
      component. RF ablation of benign nodules demonstrated volume reductions of 33-58%
      after one month and 51-85% after six months, while solving nodule-related
      clinical problems. RF ablation has recently shown positive short-term results for
      locoregional control as well as symptom improvement in patients with recurrent
      thyroid cancers. This paper reviews the basic physics, indications, patient
      preparation, devices, procedures, clinical results, and complications of RF
      ablation.

PMID- 23133450
TI  - Rapid Stereomicroscopic Imaging of HER2 Overexpression in Ex Vivo Breast Tissue
      Using Topically Applied Silica-Based Gold Nanoshells.
AB  - Tumor margin detection for patients undergoing breast conservation surgery
      primarily occurs postoperatively. Previously, we demonstrated that gold
      nanoshells rapidly enhance contrast of HER2 overexpression in ex vivo tissue
      sections. Our ultimate objective, however, is to discern HER2 overexpressing
      tissue from normal tissue in whole, nonsectioned, specimens to facilitate rapid
      diagnoses. Here, we use targeted nanoshells to quickly and effectively visualize
      HER2 receptor expression in intact ex vivo human breast tissue specimens. Punch
      biopsies of human breast tissue were analyzed after a brief 5-minute incubation
      with and without HER2-targeted silica-gold nanoshells using two-photon microscopy
      and stereomicroscopy. Labeling was subsequently verified using reflectance
      confocal microscopy, darkfield hyperspectral imaging, and immunohistochemistry to
      confirm levels of HER2 expression. Our results suggest that anti-HER2 nanoshells
      used in tandem with a near-infrared reflectance confocal microscope and a
      standard stereomicroscope may potentially be used to discern HER2-overexpressing
      cancerous tissue from normal tissue in near real time and offer a rapid
      supplement to current diagnostic techniques.

PMID- 23133451
TI  - New treatment in advanced thyroid cancer.
AB  - Thyroid cancer is the most common endocrine tumor. Thyroidectomy, radioactive
      iodine, and TSH suppression represent the standard treatment for differentiated
      thyroid cancer. Since chemotherapy has been shown to be unsuccessful in case of
      advanced thyroid carcinomas, the research for new therapies is fundamental. In
      this paper, we reviewed the recent literature reports (pubmed, medline, EMBASE
      database, and abstracts published in meeting proceedings) on new treatments in
      advanced nonmedullary and medullary thyroid carcinomas. Studies of many tyrosine
      kinase inhibitors as well as antiangiogenic inhibitors suggest that patients with
      thyroid cancer could have an advantage with new target therapy. We summarized
      both the results obtained and the toxic effects associated with these treatments
      reported in clinical trials. Reported data in this paper are encouraging, but
      further trials are necessary to obtain a more effective result in thyroid
      carcinoma treatment.

PMID- 23133452
TI  - Features of Human Herpesvirus-6A and -6B Entry.
AB  - Human herpesvirus-6 (HHV-6) is a T lymphotropic herpesvirus belonging to the
      Betaherpesvirinae subfamily. HHV-6 was long classified into variants A and B (HHV
      6A and HHV-6B); however, recently, HHV-6A and HHV-6B were reclassified as
      different species. The process of herpesvirus entry into target cells is
      complicated, and in the case of HHV-6A and HHV-6B, the detailed mechanism remains
      to be elucidated, although both viruses are known to enter cells via endocytosis.
      In this paper, (1) findings about the cellular receptor and its ligand for HHV-6A
      and HHV-6B are summarized, and (2) a schematic model of HHV-6A's replication
      cycle, including its entry, is presented. In addition, (3) reports showing the
      importance of lipids in both the HHV-6A envelope and target-cell membrane for
      viral entry are reviewed, and (4) glycoproteins involved in cell fusion are
      discussed.

PMID- 23133453
TI  - Tilted implants for full-arch rehabilitations in completely edentulous maxilla: a
      retrospective study.
AB  - Purpose. The aims of this study were to assess the treatment outcome of
      immediately loaded full-arch fixed bridges anchored to both tilted and axially
      placed implants in the edentulous maxilla and to evaluate the incidence of
      biological and prosthetic complications. Materials and Methods. Thirty-four
      patients (18 women and 16 men) were included in the study. Each patient received
      a maxillary full-arch fixed bridge supported by two axial implants and two distal
      tilted implants. A total of 136 implants were inserted. Loading was applied
      within 48 hours of surgery and definitive restorations were placed 4 to 6 months
      later. Patients were scheduled for followup at 6, 12, 18, and 24 months and
      annually up to 5 years. At each followup plaque level and bleeding scores were
      assessed and every complication was recorded. Results. The overall follow-up
      range was 12 to 73 months (mean 38.8 months). No implant failures were recorded
      to date, leading to a cumulative implant survival rate of 100%. Biological
      complications were recorded such as alveolar mucositis (11.8% patients), peri
      implantitis (5.9% patients), and temporomandibular joint pain (5.9% patients).
      The most common prosthetic complications were the fracture or detachment of one
      or multiple acrylic teeth in both the temporary (20.6% patients) and definitive
      (17.7% patients) prosthesis and the minor acrylic fractures in the temporary
      (14.7% patients) and definitive (2.9% patients) prosthesis. Hygienic
      complications occurred in 38.2% patients. No patients' dissatisfactions were
      recorded. Conclusions. The high cumulative implant survival rate indicates that
      this technique could be considered a viable treatment option. An effective recall
      program is important to early intercept and correct prosthetic and biologic
      complications in order to avoid implant and prosthetic failures.

PMID- 23133454
TI  - Prevalence and Antimicrobial Resistance of Thermophilic Campylobacter Isolated
      from Chicken in Cote d'Ivoire.
AB  - Thermophilic Campylobacters are major causes of gastroenteritis in human. The
      main risk factor of infection is consumption of contaminated or by cross
      contaminated poultry meat. In Cote d'Ivoire, gastroenteritis is usually observed
      but no case of human campylobacteriosis has been formally reported to date. The
      aims of this study were to determine prevalence and antimicrobial resistance of
      Campylobacter jejuni and Campylobacter coli isolated from chickens ceaca in
      commercial slaughter in Abidjan. Between May and November 2009, one hundred and
      nineteen (119) chicken caeca samples were collected and analyzed by passive
      filtration method followed by molecular identification (PCR). From these 119
      samples, 76 (63.8%) were positive to Campylobacter tests. Among the positive
      colonies, 51.3% were C. jejuni and 48.7% were C. coli. Of the 39 C. jejuni
      isolates, 79.5%, 38.5%, 17.9%, 10.3%, and 7.7% were, respectively, resistant, to
      nalidixic acid, ciprofloxacin, amoxicillin, erythromycin, and gentamicin. Among
      the 37 isolates of C. coli, 78.4%, 43.2%, 13.5%, 8.1%, and 0% were resistant,
      respectively, to the same antibiotics. In conclusion, we reported in this study
      the presence of high Campylobacter contamination of the studied chickens.
      Molecular identification of the bacteria was performed and determination of high
      resistance to antimicrobials of the fluoroquinolone family was revealed.

PMID- 23133456
TI  - A Rare Case of Pneumonia Caused by Shewanella putrefaciens.
AB  - Shewanella putrefaciens is a gram-negative, nonfermentative, oxidase positive,
      motile bacillus that produces hydrogen sulphide. It is found widely in the nature
      especially in marine environments. In some very rare cases Shewanella
      putrefaciens can be a human pathogen. It can produce a wide variety of clinical
      syndromes including bacteremia as well as skin and soft tissue infections.
      However, pneumonia due to S. putrefaciens is rare; there are a total of 4
      reported cases in the literature. We present a case of 63-year-old male who was
      presented to emergency room status after cardiac arrest, fell into sea water face
      down. On the second day of hospitalization, he was diagnosed to have pneumonia
      based on the clinical, radiological, and laboratory findings. Empirical
      antibiotic treatment with vancomycin and piperacillin/tazobactam combination was
      initiated. Gram-stained smear of endotracheal aspirate yielded gram-negative
      bacteria, and the isolate grown from endotracheal aspirate culture was identified
      as S. putrefaciens by Biomerieux API 20 NE technique. On review of the literature
      and according to culture and sensitivity results, therapy in our patient was
      changed to cefepime. Patient's pneumonia improved with treatment with cefepime.
      We believe that our patient developed pneumonia evidently caused by S.
      putrefaciens, after near drowning in sea water. The pneumonia resolved after
      treatment with cefepime.

PMID- 23133457
TI  - Of offords and steinhauers: institutional memory, the lowest form of evidence?

PMID- 23133455
TI  - TNF-alpha Polymorphisms in Juvenile Idiopathic Arthritis: Which Potential
      Clinical Implications?
AB  - Whether tumor necrosis factor alpha (TNF-alpha) gene polymorphisms (SNPs)
      influence disease susceptibility and treatment of patients with juvenile
      idiopathic arthritis (JIA) is presently uncertain. TNF-alpha is one of the most
      important cytokine involved in JIA pathogenesis. Several single nucleotide
      polymorphisms (SNPs) have been identified within the region of the TNF-alpha gene
      but only a very small minority have proven functional consequences and have been
      associated with susceptibility to JIA. An association between some TNF-alpha SNPs
      and adult rheumatoid arthritis (RA) susceptibility, severity and clinical
      response to anti-TNF-alpha treatment has been reported. The most frenquetly
      studied TNF-alpha SNP is located at -308 position, where a substitution of the G
      allele with the rare A allele has been found. The presence of the allele -308A is
      associated to JIA and to a poor prognosis. Besides, the -308G genotype has been
      associated with a better response to anti-TNF-alpha therapy in JIA patients,
      confirming adult data. Psoriatic and oligoarticular arthritis are significantly
      associated to the -238 SNP only in some works. Studies considering other SNPs are
      conflicting and inconclusive. Large scale studies are required to define the
      contribution of TNF-alpha gene products to disease pathogenesis and anti-TNF
      alpha therapeutic efficacy in JIA.

PMID- 23133458
TI  - Prevention of substance use in children/adolescents with mental disorders: a
      systematic review.
AB  - OBJECTIVE: WE CONDUCTED A SYSTEMATIC REVIEW TO ANSWER THE QUESTION: Among youth
      <=18 years of age with a mental disorder, does substance use prevention compared
      to no prevention result in reduced rates of substance use/abuse/disorder (SUD)?
      The review was requested by the Ontario Ministry of Health and Long-term Care
      through the Canadian Institutes for Health Research Evidence on Tap program.
      METHODS: A four-step search process was used: Search 1 and 2: Randomized
      controlled trials (RCTs) that evaluated a SUD prevention intervention in
      individuals with a mental disorder who were: 1) <=18 years; or, 2) any age.
      Search 3: Observational studies of an intervention to prevent SUD in those with
      mental disorder. Search 4: RCTs that evaluated a SUD primary prevention skills
      based intervention in high-risk youth <=18 years. RESULTS: Searches 1 and 2: one
      RCT conducted in youth was found; Search 3: two observational studies were found.
      All three studies reported statistically significant reductions in substance use.
      Search 4: five RCTs were found with mixed results. Methodological weaknesses
      including inadequate study power may explain the results. CONCLUSIONS: Little is
      known about effective interventions to prevent SUD in youth with a mental
      disorder. Effective SUD primary prevention programs exist and should be evaluated
      in this high-risk group.

PMID- 23133459
TI  - [Not Available].
AB  - OBJECTIVE: This study aims at examining risk factors associated with attention
      deficit/hyperactivity disorder (ADHD) such as comorbidities and adversity factors
      in members of a family with ADHD. METHODS: 137 parents of 104 children with ADHD
      and 40 parents of 34 typically developing (TD) children filled a questionnaire.
      Chi-square tests and Student tests measured the association between each group
      and items of the questionnaire as well as the differences between the groups.
      RESULTS: Statistical analysis revealed overall decreased academic performances in
      children with ADHD compared to the TD children. Furthermore, ADHD was
      substantially more associated with learning, conduct, anxiety and oppositional
      disorders relative to TD children. Learning difficulties were more frequently
      reported by fathers of children with ADHD. Mothers of children with ADHD suffered
      more from depression and anxious disorder and were taking more medication than
      their TD correspondents. CONCLUSION: The results revealed a link between parents
      and children, namely depression and anxious disorder in mothers and learning
      difficulties in fathers of children with ADHD, suggesting a familial component to
      the disorder. The low report of ADHD diagnosis in fathers of children with ADHD
      is discussed.

PMID- 23133460
TI  - Stress and relief: parents attending a respite program.
AB  - OBJECTIVE: The objectives of this study were to examine changes in stress among
      parents of children with special needs in a respite service and consider parental
      experience of the service. METHODS: Families who were enrolled in a ten-month
      centre-based respite program were invited to participate in the evaluation.
      Change in parent stress, indexed by the Parent Stress Index-Short Form (PSI-SF),
      was determined. These results were compared with findings from exploratory
      qualitative interviews with a subset of parents and a small comparison group who
      also completed the PSI-SF. RESULTS: At baseline, 69% of parents (n=45) had high
      total stress scores on the PSI-SF. No significant improvements were detected on
      parent stress over time or differences from improvements in the comparison group.
      In contrast, the subgroup of parents (n=10) who participated in the qualitative
      interviews described substantial benefits from the respite program including a
      sense of relief and having time for other activities. CONCLUSIONS: It is proposed
      that the respite program may have provided a temporary break to parents thereby
      bestowing a sense of relief, but was not adequate to impact on more chronic
      stress patterns, suggesting that these are related but separate constructs and
      experiences.

PMID- 23133461
TI  - Non-suicidal self-injury and suicidal behaviour in children and adolescents
      accessing residential or intensive home-based mental health services.
AB  - OBJECTIVE: There is a dearth of Canadian research with clinical samples of youth
      who self-harm, and no studies could be located on self-harm in children and youth
      accessing residential or intensive home-based treatment. The purposes of this
      report were to explore the proportion and characteristics of children and youth
      identified as self-harming at admission by clinicians compared to youth not
      identified as self-harming, compare self-harming children to adolescents, and to
      compare caregiver ratings of self-harm at intake to clinician ratings at
      admission. METHOD: This report was developed from a larger longitudinal,
      observational study involving 210 children and youth accessing residential and
      home-based treatment and their caregivers in partnership with five mental health
      treatment centres in southwestern Ontario. Agency data were gleaned from files,
      and caregivers reported on symptom severity at 12 to 18 months and 36 to 40
      months post-discharge. RESULTS: Fifty-seven (34%) children and youth were
      identified as self-harming at admission. The mean age was 11.57 (SD 2.75). There
      were statistically significant differences on symptom severity at intake between
      those identified as self-harming and those not so identified; most of these
      differences were no longer present at follow up. Children were reported to have
      higher severity of conduct disorder symptoms than adolescents at intake, and
      there was some consistency between caregiver-rated and clinician-rated self-harm.
      Children were reported to engage in a wide range of self-harming behaviours.
      CONCLUSION: These findings suggest that youth who were identified as self-harming
      at admission have elevated scores of symptom severity, self-harm can occur in
      young children and while many improve, there remains a concern for several
      children and youth who did not improve by the end of service. Children engage in
      some of the same types of self-harm behaviours as adolescents, and they also
      engage in behaviours unique to children.

PMID- 23133462
TI  - Efficacy of Methylphenidate in ADHD Children across the Normal and the Gifted
      Intellectual Spectrum.
AB  - OBJECTIVE: This study evaluates whether attention-deficit/hyperactivity disorder
      (ADHD) children with a borderline intelligence quotient (IQ) (70<=FSIQ<80),
      normal IQ (80<=FSIQ<120) and high IQ (FSIQ>=120) respond differently to
      psychostimulant treatment. METHOD: 502 children, aged 6 to 12 years, with an IQ
      range from 70 to 150 participated in a two-week, double-blind, placebo
      controlled, crossover methylphenidate (MPH) trial. RESULTS: In addition to
      differences in socioeconomic background and parental education, higher IQ
      children were found to present with less severe symptoms. No significant
      differences were found with regards to treatment response. CONCLUSION: ADHD
      children within the normal and high levels of intellectual functioning all
      respond equally to psychostimulant treatment, and that proper medication
      management is necessary for all children with the disorder.

PMID- 23133463
TI  - Youth are more Vulnerable to False Memories than Middle-Aged Adults due to
      Liberal Response Bias.
AB  - OBJECTIVE: Numerous studies show changes in vulnerability to false memory
      formation across development and into senescence. No study, however, has compared
      false memory formation in the critical transition period spanning late
      adolescence to middle adulthood. METHOD: Using the Deese-Roediger-McDermott (DRM)
      paradigm, we explored the effects of age and of emotion on false memory formation
      in youth (16 to 23 years of age) and in middle-aged adults (29 to 58 years of
      age). RESULTS: We found that youth endorsed more false lure items than middle
      aged adults. This increased vulnerability to false memory formation stemmed from
      a more liberal response bias in the younger group. CONCLUSIONS: Youth have a more
      liberal response criterion than middle-aged adults that contributes to an
      increased vulnerability to false memory formation. Subsequent age-related changes
      in response bias may reflect the maturation of frontal and temporal regions. In
      youth, a more liberal response bias may contribute to the heightened propensity
      for poor decision-making seen in this population.

PMID- 23133464
TI  - Media use and health outcomes in adolescents: findings from a nationally
      representative survey.
AB  - OBJECTIVE: Examine the association between quantity of media use and health
      outcomes in adolescents. METHOD: Multiple logistic regression analyses were
      conducted with the Canadian Community Health Survey 1.1 (youth aged 12-19
      (n=9137)) to determine the association between hours of use of television/videos,
      video games, and computers/Internet, and health outcomes including depression,
      alcohol dependence, binge drinking, suicidal ideation, help-seeking behaviour,
      risky sexual activity, and obesity. RESULTS: Obesity was associated with frequent
      television/video use (Adjusted Odds Ratio (AOR) 1.10). Depression and risky
      sexual behaviour were less likely in frequent video game users (AOR 0.87 and
      0.73). Binge drinking was less likely in frequent users of video games (AOR 0.92)
      and computers/Internet (AOR 0.90). Alcohol dependence was less likely in frequent
      computer/Internet users (AOR 0.89). CONCLUSIONS: Most health outcomes, except for
      obesity, were not associated with using media in youth. Further research into the
      appropriate role of media will help harness its full potential.

PMID- 23133465
TI  - Health Information Preference among Youth and Caregivers related to Second
      Generation Antipsychotic Treatment.
AB  - OBJECTIVE: To determine the health information-seeking preferences of youth with
      mental health challenges and their caregivers, focusing on health literacy needs
      related to second-generation antipsychotics (SGAs). METHODS: One hundred fifty
      two youth and 158 caregivers attending outpatient psychiatry clinics at BC
      Children's Hospital between February 2009 and December 2010 completed a SGA
      health literacy survey. RESULTS: Youth and caregivers placed emphasis on
      understanding the benefits and side effects of SGA-treatment, along with
      strategies to prevent potential side effects. While psychiatrists were viewed as
      a crucial source of information by both groups, pharmacists were an under
      utilized resource by youth. Both youth and caregivers preferred brochures from
      healthcare providers, websites, and support groups to access health information;
      however, preferences diverged among other activities. Specifically, youth
      favoured practical, "hands-on" programs such as cooking and exercise classes,
      whereas caregivers showed greater interest in didactic presentations and
      conferences. Sex differences were observed in receptiveness towards certain
      programs and resources. CONCLUSIONS: The findings from this study support the
      inclusion of caregivers and youth of both sexes with mental health conditions in
      the future development of educational resources related to medications such as
      SGAs. Health literacy strategies need to be multi-faceted, and utilize mixed
      methods to ensure broad reach and applicability.

PMID- 23133467
TI  - IL-23 and IL-27 Levels in Macrophages Collected from Peripheral Blood of Patients
      with Healing Vs Non-Healing Form of Cutaneous Leishmaniasis.
AB  - BACKGROUND: In this study the level of IL-23 and IL-27 produced by macrophages
      derived from peripheral blood mononuclear cell culture collected from patients
      with healing or non-healing form of cutaneous leishmaniasis lesion were compared
      before and after treatment with live Leishmania to explore whether IL-23 or IL-27
      plays any role in healing process of cutaneous lesions induced by L. major.
      METHODS: Twenty patients resident in Isfahan Province, with healing or non
      healing form of cutaneous leishmaniasis lesion caused by Leishmania major
      participated in this study. In vitro productions of IL-23 and IL-27 by peripheral
      blood derived macrophages, before and after stimulation with live L. major
      (MRHO/IR/75/ER) promastigotes were evaluated using ELISA method. Patient with
      healing form of lesion received no treatment and patient with non-healing form of
      lesion received at least 2 courses of glucantime. RESULTS: The mean production of
      IL-23 and IL-27 from macrophages of patients with healing form of lesion was
      significantly higher than patients with non-healing form of lesion. The levels of
      IL-23 and IL-27 in culture supernatants before and after stimulation in healing
      form of CL was significantly higher than non- healing form of CL (P < 0.001).
      CONCLUSION: IL-23 and IL-27 might play a role in human leishmaniasis and further
      studies are needed to understand the role of IL-23 and IL-27 in leishmaniasis.

PMID- 23133468
TI  - Sequence Analysis of Different Domains of Plasmodium vivax Apical Membrane
      Antigen (PvAMA-1 gene) Locus in Iran.
AB  - BACKGROUND: Plasmodium vivax is responsible for approximately 80 million malaria
      cases in the world. Apical membrane antigen1 (AMA-1) is a type I integral
      membrane protein present in all Plasmodium species. AMA-1 interferes in critical
      steps of invasion of human hepatocytes by sporozoites and red blood cells by
      merozoites and is one of the most immunodominant antigens for eliciting a
      protective immune response in human. It is considered as a promising antigen for
      inclusion in a vaccine against P. vivax. Since more knowledge is needed to
      lighten the scope of such antigen we compared genetic variation in P. vivax AMA
      1from an Iranian isolate with those reported from some of the other malarious
      countries so far. METHODS: P. vivax genomic DNA was extracted from the whole
      blood of an Iranian patient with patent P. vivax infection. The nucleotide
      sequence for 446 amino acid (AA) residues (42-488 of PvAMA-1) was amplified by
      PCR and cloned in pUC19 vector for sequencing. RESULTS: Sequence analysis of the
      antigen showed a high degree of identity (99%) with strong homology to the PvAMA
      1 gene of P. vivax S3 and SKO814 isolates from India and Korea (Asian isolates)
      respectively, and 96% similarity with P. vivax Sal-1 AMA-1 gene from El Salvador.
      CONCLUSIONS: We cloned and characterized three domains of PvAMA-1 gene from an
      Iranian patient. Predicted protein sequence of this gene showed some
      discrepancies in corresponding protein in comparing with similar genes reported
      from other malarious countries.

PMID- 23133466
TI  - Latent toxoplasmosis and human.
AB  - Toxoplasmosis is one of the most common parasitic diseases worldwide. Although
      estimated that one third of the world's population are infected with Toxoplasma
      gondii, but the most common form of the disease is latent (asymptomatic). On the
      other hand, recent findings indicated that latent toxoplasmosis is not only
      unsafe for human, but also may play various roles in the etiology of different
      mental disorders. This paper reviews new findings about importance of latent
      toxoplasmosis (except in immunocompromised patients) in alterations of behavioral
      parameters and also its role in the etiology of schizophrenia and depressive
      disorders, obsessive-compulsive disorder, Alzheimer's diseases and Parkinson's
      disease, epilepsy, headache and or migraine, mental retardation and intelligence
      quotients, suicide attempt, risk of traffic accidents, sex ratio and some
      possible mechanisms of T. gondii that could contribute in the etiology of these
      alterations.

PMID- 23133469
TI  - Amphistome species in cattle in South coast of caspian sea.
AB  - BACKGROUND: Knowledge about the amphistomid fauna in Iranian domestic ruminants
      depends on the studies conducted almost 30 years ago. The last situation in
      cattle is introduced here in the provinces in south coast of Caspian Sea.
      METHODS: Amphistomid species were collected from cattle at slaughter houses of
      the provinces Gilan and Mazanderan in 2010. Median sagittal sections were
      prepared by the conventional method. Species were identified by the
      histomorphological pecularities of the muscular argans. RESULTS: Five amphistomid
      species, Paramphistomum cevri, P. gotoi, Calicophoron calicophorum, Carmyerius
      spatiosus and Gastrothylax compressus, recovered. Calicophoron calicophorum is a
      new species for Iran. Criteria used in identification of the species were
      illustrated. CONCLUSION: Iran has a rich amphistomid fauna and mostly under the
      influence of oriental conditions.

PMID- 23133470
TI  - Absence of asymptomatic malaria infection in endemic area of bashagard district,
      hormozgan province, iran.
AB  - BACKGROUND: A successful malaria elimination program calls for enough attention
      to parasite carriers, especially asymptomatic malaria, as well as the diagnosis
      and treatment of clinical cases. Asymptomatic malaria is an infection that
      patients do not show any symptom; thus, these patients play critical role in the
      concept of an elimination program. The current investigation was conducted to
      evaluate the presence of these cases in Bashagard District, formerly a high
      malaria transmission area in Hormozgan Province, Iran. METHODS: Blood samples (n
      = 500) were collected from symptomless individuals residing in Bashagard to
      evaluate Plasmodium infection by using microscopic, serological and nested-PCR
      techniques. RESULTS: Regarding the microscopic and nested-PCR analysis, no
      asymptomatic infection was detected among studied individuals. Totally, 1% of the
      studied population (5 of 500) had anti PvMSP-1(19)-specific IgG antibody;
      however, only 0.2% (1 of 500) of the individuals was seropositive to recombinant
      PfMSP-1(19), using ELISA. CONCLUSION: This study showed no asymptomatic malaria
      infection in the studied population; hence malaria elimination is feasible and
      can be successfully carried out in this region.

PMID- 23133471
TI  - Spatial distribution and molecular identification of leishmania species from
      endemic foci of South-eastern iran.
AB  - BACKGROUND: Cutaneous leishmaniasis constitutes a major public health problem in
      many parts of the world including Iran. The primary objective of this study was
      to identify Leishmania species in endemic districts of Kerman Province, south
      eastern Iran. METHODS: This study was conducted by random sampling as cross-
      sectional descriptive between 2008 and 2010. Overall, 203 skin scraping smears
      were taken from the patients. Nested -PCR was performed to amplify variable
      minicircle fragments of Leishmania kDNA. RESULTS: Bam was the most infected
      district (71.1%), followed by Kerman (14.7%), Jiroft (5.4%), Baft (2.7%), Sirjan
      (1.6%), Shahr-e Babak (1.5%) and others (3.0%). L. tropica was the most common
      species identified (194 cases, 95.6%), while L. major was found in only 9 cases
      (4.4%). Of 203 identified patients, all species in Bam (l07 cases), Kerman (32
      cases), Jiroft (l6 cases) and Shahr-e- Babak (l1 cases) were detected as L.
      tropica, whereas infected subjects in Baft and Sirjan showed L. tropica or L.
      major. Characterization of Leishmania species resulted in generation of 750 bp
      and 560 bp fragments, corresponding to those of L. tropica and L. major,
      respectively. CONCLUSION: L. tropica is the main species (95.6%) caused ACL in
      endemic areas of Kerman Province; however L. major is present in low level
      (4.4%).

PMID- 23133472
TI  - Cryptosporidium spp. Infection in human and domestic animals.
AB  - BACKGROUND: Cryptosporidium spp. is a coccidian parasite infected humans and
      animals. Prevalence rate of Cryptosporidium spp. infection associated with is
      some parameters such as sampling, age, season, country and contact to domestic
      animals. This study aimed to determine Cryptosporidium spp. Infection in humans
      and some animals in rural areas of Shushtar district from Khuzestan Province,
      south- west of Iran. METHODS: In this study, Stool specimens were randomly
      collected from 45 cattle, 8 buffalos, 35 calves, 22 turkeys, 3 sheep, 2 geese as
      well as 62 humans in different seasons selected from rural areas of Shushtar
      district located in Khuzestan in the south- west of Iran from August 2009 to
      April 2011. The collected stool samples were examined by modified Ziehl-Neelsen
      staining method. RESULTS: Altogether, 68/115 (59.1%) domestic animals and 9/62
      (14.5%) of humans were showed Cryptosporidium spp. infection in the study areas.
      CONCLUSION: In this study we found the high frequency of Cryptosporidium spp.
      infection in the studied areas.

PMID- 23133473
TI  - Establishment of a Modified in Vitro Cultivation of Protoscoleces to Adult
      Echinococcus granulosus; an Important Way for New Investigations on Hydatidosis.
AB  - BACKGROUND: Echinococcus granulosus, a zoonotic cestode parasite, causative agent
      of hydatid cyst is endemic in many parts of the world including the Middle East.
      Study on different aspects of this parasite is very important and valuable.
      However, working with adult worms which their habitat situated in the small
      intestine of canids, is dangerous and risky. Achieving such risky situation needs
      a controlled condition which is cultivation of the organisms in the laboratory.
      In this regard, cultivation of E. granulosus protoscoleces leading to adult worms
      was established in the laboratory for the first time in Iran. METHODS: Under
      aseptic conditions a number of protoscoleces were cultivated in diphasic S.10E.H
      medium using CO2 incubator to produce adult worms. RESULTS: Different forms of
      parasites including pre-segmentation stages (PS1 - PS4) and segmentation stages
      (S5-S8) and developing stages in segmented worms (S10-S11) were observed and
      evaluated in these medium. Finally adult worms contained four proglottids with a
      large and distinct genital pore were observed 50-55 days post cultivation. These
      parasites do not produce fertile eggs and conclusively do not have risk of
      hydatid disease transmission to the researchers. CONCLUSION: The mentioned method
      for producing E. granulosus adult worms can open a new window for researches and
      facilitate working on different aspects of hydatidosis especially for diagnosis,
      protection and treatment studies.

PMID- 23133474
TI  - Prevalence of Schistosoma intercalatum and S. haematobium Infection among Primary
      Schoolchildren in Capital Areas of Democratic Republic Of Sao Tome and Principe,
      West Africa.
AB  - BACKGROUND: A parasitological survey of Schistosoma haematobium and S.
      intercalatum infection among primary schoolchildren in capital area of Democratic
      Republic of Sao Tome and Principe (DRSTP) was undertaken. METHODS: Subjects with
      positive infection were confirmed by the detection of S. haematobium ova in the
      urine or S. intercalatum ova in the stool by using centrifugation concentration
      or merthiolate-iodine-formalin concentration method. Totally, 252 urine and stool
      samples, respectively, were obtained from apparently healthy schoolchildren, of
      which 121 from boys (9.8 +/- 1.4 yr) and 131 from girls (9.7 +/- 1.3 yr).
      RESULTS: None of participating schoolchildren were found having S. haematobium
      ova in the urinary specimen. While, among 4 primary schools studied, only
      schoolchildren from Saint Marcal were detected with S. intercalatum ova in the
      fecal specimen, making the overall prevalence of S. intercalatum infection among
      schoolchildren was 2.4% (6/252) and girls had insignificantly higher prevalence
      (3.1%, 4/131) than that (1.7%, 2/121) in boys (chi(2) = 0.5, P = 0.5).
      CONCLUSION: Water control and sanitation as well as snails eliminated by
      molluscicides are urgently needed to reduce S. intercalatum infection in DRSTP
      inhabitants.

PMID- 23133475
TI  - Parasites of Some Freshwater Fish from Armand River, Chaharmahal va Bakhtyari
      Province, Iran.
AB  - BACKGROUND: The aim of this study was to detect the occurrence of parasites in
      fish in Armand River, Chaharmahal va Bakhtyari Province regarding the importance
      of native fish population in the river. METHODS: The occurrence of parasites was
      investigated in 6 native fish (Capoeta capoeta, C. damascina, C. aculeta, Barbus
      barbulus, B. grypus and Glyptothorax silviae) collected from the current main
      channel of the river from autumn 2009 to summer 2010. RESULTS: 63.7% of the
      studied fishes were infected with 19 parasite species including Ichthyophthirius
      multifiliis, Myxobolus musayevi, Dactylogyrus lenkorani, D. gracilis, D. pulcher,
      D. chramuli, D. akaraicus, D. skrjabiensis, two species of Gyrodactylus,
      Paradiplozoon sp., Lamproglena compacta, Copepodid of Lernaea cyprinacea,
      Ergasilus sp., Allocreadium isoporum, Allocreadium pseudaspii, Kawia sp.,
      Bothriocephalus gowkongensis and Rhabdochona denudata. The infection rate was
      significantly higher (P<0.05) in C.aculeata while the maximum parasite diversity
      was found in C.damascina. The infection rate was also significantly different in
      four seasons (P<0.05) but no significant differences were found among fishes with
      different weight and length. CONCLUSION: High prevalence of Ichthyophthirius
      multifiliis and Rhabdochona denudata may affect native fish population.
      Monogenean parasites Dactylogyrus akaraicus and D. skrjabiensis collected from B.
      barbulus and C. capoeta are reported for the first time in Iran. B. barbulus is
      also reported as a new host for aforementioned parasites.

PMID- 23133476
TI  - Prevalence of Cryptosporidium spp. in Camels and Involved People in Yazd
      Province, Iran.
AB  - BACKGROUND: Although infection of dromedary camels with Cryptosporidium spp. is
      rare in Iran, it is considered a zoonotic threat to the keepers and herders of
      camels. Thus we investigated the prevalence of Cryptosporidium in these two hosts
      in Yazd Province, a semi-arid region in center of Iran. METHODS: This study was
      conducted during 4 seasons (winter 2008, summer 2009, winter 2009 and summer
      2010). Fecal samples (n=200) were collected from live camels. Also, 100 abomasal
      mucosa and related fecal samples of the slaughtered camels were investigated.
      Stool samples from 100 individuals who were in persistent contact with camels
      were also obtained. After staining by modified Ziehl-Neelsen method, the prepared
      specimens were studied microscopically. Results were analyzed using SPSS 16.
      RESULTS: The rate of infection in feces and abomasal mucosa of camels were 20.33%
      and 12%, respectively. In addition, simultaneous fecal and mucosal infection was
      detected in 3 cases in winter. Statistical analyses showed no significant
      relation between infection and age of camels, as well as their sex and the
      season. Cryptosporidiosis in people who were in long-term contact with camels was
      also investigated microscopically by obtaining stool samples of 100 individuals
      (50 in summers, 50 in winters), 24 of them being infected with Cryptosporidium
      spp. The rate of infection was higher in winter than summer (16/50 compared with
      8/50). CONCLUSION: The prevalence of Cryptosporidium spp. in camels and involved
      humans in Yazd Province is relatively considerable and of public health
      importance.

PMID- 23133477
TI  - Epidemiological and Clinical Study of Infested Cases with Pediculus capitis and
      P. corporis in Khorasan-e-Razavi, Iran.
AB  - BACKGROUND: Pediculosis (head lice) is considered as one of the most common
      health problems of the students in primary schools. The purpose of this study was
      to survey the prevalence rate of the infestation in the schools of Gonabad City
      (south of Khorasan-e-Razavi Province) to prevent its outbreak by on-time
      planning. METHODS: In this retrospective-descriptive study, data were collected
      from the files of recorded health examinations of 55,997 female and male students
      of Gonabad City. We surveyed the infested cases to Pediculus capitis and P.
      corporis during 2006-2010. We used schools health unit of the city health center
      and review reports of infestation to head lice and body lice in cumulative
      centers. RESULTS: The reports showed 398 cases of P. capitis and 3 P. corporis
      infestations, which 91.5% were female (P <0.05). Generally 46.4% were from rural
      and 63.6% were from urban areas (P <0.05). 71.3% of the infestation to head lice
      was from the last month and the rest had recently been infested. The most age
      group being infested were students of 6-10 years old and the lowest were >17 yr.
      CONCLUSION: Pediculosis infestation has become a major health problem in primary
      school students in south of Khorasan-e-Razavi.

PMID- 23133478
TI  - Novel in Vitro Efficiency of Chitosan Biomolecule against Trichomonas gallinae.
AB  - BACKGROUND: Development of new natural agents for parasitic diseases treatment
      has unexpectedly increased to overcome effectively against emergence and re
      emergence of parasitic diseases, the appearance of drug resistant organisms and
      toxic side effects of current agents. The aim of the study was to evaluate
      antiprotozoal activities of chitosan biomolecule on trophozoites of Trichomonas
      gallinae. METHODS: The antitrichomonal activity of various low molecular weight
      chitosan concentrations including 125, 250, 500 and 1250 ug ml(-1) against T.
      gallinae trophozoites cultured in trypticase-yeast extract-maltose medium
      supplemented with heat-inactivated cold horse serum was evaluated in vitro.
      Samples containing medium without chitosan were also assayed as controls.
      RESULTS: The mortality rates at 0, 3 and 6 h post treatment with all
      concentrations were significantly different from control group (P<0.05). Treated
      trophozoites showed more susceptibility to the highest concentration reaching
      mortality rate of 100% at 3h post inoculation. However, at this time, results for
      125, 250 and 500 ug ml(-1) were 93%, 95% and 96.7%, respectively. CONCLUSION: The
      results demonstrate that the application of chitosan biomolecule is a promising
      option for treatment of trichomoniasis in pigeons.

PMID- 23133479
TI  - Sequence Diversity in tRNA Gene Locus A-L among Iranian Isolates of Entamoeba
      dispar.
AB  - BACKGROUND: A number of methods for detecting diversity in Entamoeba have been
      described over the years. In the present study the genetic polymorphism of
      noncoding locus A-L was analyzed using PCR and sequencing in order to clarify the
      genotypic differences among E. dispar isolates. METHODS: A total of 28 E. dispar
      from patients with gastrointestinal symptoms were determined and the genomic DNA
      was extracted directly from stool. For genotype analysis; Locus A-L was amplified
      by PCR and PCR products were sequenced. The sequences obtained were edited
      manually and aligned using Gene Runner software. RESULTS: With sequencing of PCR
      products a reliable genetic diversity in size, number and position of the repeat
      units were observed among the Iranian E. dispar isolates in locus A-L gene.
      Sequences showed variation in length from 448bp to 507bp and seven distinct types
      were identified. CONCLUSION: The genetic diversity of loci like A-L shows them to
      be suitable for epidemiological studies such as the characterization of the
      routes of transmission of these parasites in Iran.

PMID- 23133480
TI  - Occurrence of Nasal Nosocomial Myiasis by Lucilia sericata (Diptera:
      Calliphoridae) In North of Iran.
AB  - We report a case of human nasal nosocomial myiasis in a 69-year-old rural man
      with numerous live maggots in nostrils. The patient was admitted in Emergency
      Ward due to dyspnea. After 72 hours the companion of patient discovered larva.
      The presence of the third instar larva indicated that the infestation was not
      more than three days. The collected instars were cleared, fixed and morphological
      studies then were carried out precisely and the larva was identified as Lucilia
      sericata.

PMID- 23133482
TI  - Renal scar formation after urinary tract infection in children.
AB  - Urinary tract infection (UTI) is a common bacterial illness in children. Acute
      pyelonephritis in children may lead to renal scarring with the risk of later
      hypertension, preeclampsia during pregnancy, proteinuria, and renal
      insufficiency. Until now, vesicoureteral reflux (VUR) has been considered the
      most important risk factor for post-UTI renal scar formation in children. VUR
      predisposes children with UTI to pyelonephritis, and both are associated with
      renal scarring. However, reflux nephropathy is not always acquired; rather, it
      reflects reflux-associated congenital dysplastic kidneys. The viewpoint that
      chronic kidney disease results from renal maldevelopment-associated VUR has led
      to questioning the utility of any regimen directed at identifying or treating
      VUR. Despite the recognition that underlying renal anomalies may be the cause of
      renal scarring that was previously attributed to infection, the prevention of
      renal scarring remains the goal of all therapies for childhood UTI. Therefore,
      children at high risk of renal scar formation after UTI should be treated and
      investigated until a large clinical study and basic research give us more
      information.

PMID- 23133481
TI  - Enterovirus infection in Korean children and anti-enteroviral potential candidate
      agents.
AB  - Although most enterovirus infections are not serious enough to be life
      threatening, several enteroviruses such as enterovirus 71 are responsible for
      severe, potentially life-threatening disease. The epidemic patterns of
      enteroviruses occur regularly during the year, but they may change due to
      environmental shifts induced by climate change due to global warming. Therefore,
      enterovirus epidemiological studies should be performed continuously as a basis
      for anti-viral studies. A great number of synthesized antiviral compounds that
      work against enteroviruses have been developed but only a few have demonstrated
      effectiveness in vivo. No proven effective antiviral agents are available for
      enterovirus disease therapy. The development of a new antiviral drug is a
      difficult task due to poor selective toxicity and cost. To overcome these
      limitations, one approach is to accelerate the availability of other existing
      antiviral drugs approved for antiviral effect against enteroviruses, and the
      other way is to screen traditional medicinal plants.

PMID- 23133483
TI  - Puromycin aminonucleoside modulates p130Cas of podocytes.
AB  - PURPOSE: Puromycin aminonucleoside (PAN) specifically injures podocytes, leading
      to foot process effacement, actin cytoskeleton disorganization, and abnormal
      distribution of slit diaphragm proteins. p130Cas is a docking protein connecting
      F-actin fibers to the glomerular basement membrane (GBM) and adapter proteins in
      glomerular epithelial cells (GEpCs; podocytes). We investigated the changes in
      the p130Cas expression level in the PAN-induced pathological changes of podocytes
      in vitro. METHODS: We observed changes in the p130Cas expression in cultured rat
      GEpCs and mouse podocytes treated with various concentrations of PAN and
      antioxidants, including probucol, epigallocatechin gallate (EGCG), and vitamin C.
      The changes in the p130Cas expression level were analyzed using confocal
      immunofluorescence imaging, Western blotting, and polymerase chain reaction.
      RESULTS: In the immunofluorescence study, p130Cas showed a diffuse cytoplasmic
      distribution with accumulation at distinct sites visible as short stripes and
      colocalized with P-cadherin. The fluorescences of the p130Cas protein were
      internalized and became granular by PAN administration in a dose-dependent
      manner, which had been restored by antioxidants, EGCG and vitamin C. PAN also
      decreased the protein and mRNA expression levels of p130Cas at high doses and in
      a longer exposed duration, which had been also reversed by antioxidants.
      CONCLUSION: These findings suggest that PAN modulates the quantitative and
      distributional changes of podocyte p130Cas through oxidative stress resulting in
      podocyte dysfunction.

PMID- 23133484
TI  - Clinical features and surgical outcomes of complete transposition of the great
      arteries.
AB  - PURPOSE: This single-center study aimed to assess the clinical features and
      surgical approaches and outcomes of complete transposition of the great arteries
      (TGA). METHODS: TGA patients who had undergone surgical correction at the
      Kyungpook National University Hospital from January 2000 to December 2010, were
      retrospectively evaluated for patient characteristics, clinical manifestation,
      preoperative management, intraoperative findings, postoperative progress, and
      follow-up status. RESULTS: Twenty-eight patients (17 boys and 11 girls, mean
      age=10.6+/-21.5 days) were included and were categorized as follows: group I, TGA
      with intact ventricular septum (n=13); group II, TGA with ventricular septal
      defect (VSD, n=12); and group III, TGA/VSD with pulmonary stenosis (n=3). Group I
      underwent the most intensive preoperative management (balloon atrial septostomy
      and prostaglandin E1 medication). Group II showed the highest incidence of heart
      failure (P<0.05). Usual and unusual coronary anatomy patterns were observed in 20
      (71%) and 8 patients, respectively. Arterial and half-turned truncal switch
      operations were performed in 25 and 3 patients (Group III), respectively.
      Postoperative complications included cardiac arrhythmias (8 patients), central
      nervous system complications (3 patients), acute renal failure (1 patient),
      infections (3 patients), and cardiac tamponade (1 patient), and no statistically
      significant difference was observed between the groups. Group II showed the
      mildest aortic regurgitation on follow-up echocardiograms (P<0.05). One patient
      underwent reoperation, and 1 died. The overall mortality rate was 4%. CONCLUSION:
      Our study showed favorable results in all the groups and no significant
      difference in postoperative complication, reoperation, and mortality among the
      groups. However, our results were inadequate to evaluate the risk factors for
      reoperation and mortality owing to the small number of patients and short follow
      up duration.

PMID- 23133485
TI  - Cognitive and other neuropsychological profiles in children with newly diagnosed
      benign rolandic epilepsy.
AB  - PURPOSE: Although benign rolandic epilepsy (BRE) is a benign condition, it may be
      associated with a spectrum of behavioral, psychiatric, and cognitive disorders.
      This study aimed to assess the cognitive and other neuropsychological profiles of
      children with BRE. METHODS: In total, 23 children with BRE were consecutively
      recruited. All children underwent sleep electroencephalography (EEG) and were
      assessed on a battery of comprehensive neuropsychological tests including the
      Korean versions of the Wechsler intelligence scale for children III, frontal
      executive neuropsychological test, rey complex figure test, Wisconsin card
      sorting test, attention deficit diagnostic scale, and child behavior checklist
      scale. RESULTS: The study subjects included 13 boys and 10 girls aged 9.0+/-1.6
      years. Our subjects showed an average monthly seizure frequency of 0.9+/-0.7, and
      a majority of them had focal seizures (70%). The spike index (frequency/min) was
      4.1+/-5.3 (right) and 13.1+/-15.9 (left). Of the 23 subjects, 9 showed frequent
      spikes (>10/min) on the EEG. The subjects had normal cognitive and frontal
      executive functions, memory, and other neuropsychological sub-domain scores, even
      though 8 children (35%) showed some evidence of learning difficulties, attention
      deficits, and aggressive behavior. CONCLUSION: Our data have limited predictive
      value; however, these data demonstrate that although BRE appears to be benign at
      the onset, children with BRE might develop cognitive, behavioral, and other
      psychiatric disorders during the active phase of epilepsy, and these problems may
      even outlast the BRE. Therefore, we recommend scrupulous follow-up for children
      with BRE.

PMID- 23133486
TI  - LIN28B polymorphisms are associated with central precocious puberty and early
      puberty in girls.
AB  - PURPOSE: Single-nucleotide polymorphism (SNP) markers within LIN28B have been
      reported to be related to the timing of pubertal growth. However, no study has
      investigated the frequency of genetic markers in girls with precocious puberty
      (PP) or early puberty (EP). This study aimed to determine the frequency of
      putative genetic markers in girls with PP or EP. METHODS: Genomic DNAs were
      obtained from 77 and 109 girls that fulfilled the criteria for PP and EP,
      respectively. The controls in this study were 144 healthy volunteers between 20
      and 30 years of age. The haplotypes were reconstructed using 11 SNPs of LIN28B,
      and haplotype association analysis was performed. The haplotype frequencies were
      compared. Differences in the clinical and laboratory parameters were analyzed
      according to the haplotype dosage. RESULTS: Eleven SNPs in LIN28B were all
      located in a block that was in linkage disequilibrium. The haplotype could be
      reconstructed using 2 representative SNPs, rs4946651 and rs369065. The AC
      haplotype was less frequently observed in the PP group than in the controls
      (0.069 vs. 0.144, P=0.010). The trend that girls with non-AC haplotypes tended to
      have earlier puberty onset (P=0.037) was illustrated even in the EP+PP patient
      group by Kaplan-Meier analysis. CONCLUSION: The results of the present study
      showed that non-AC haplotypes of LIN28B had a significant association with PP in
      girls.

PMID- 23133487
TI  - Complete trisomy 14 mosaicism: first live-born case in Korea.
AB  - Trisomy 14 mosaicism is a rare chromosome disorder characterized by delayed
      development, failure to thrive, and facial dysmorphism. Only approximately 30
      trisomy 14 mosaicism cases have been reported in the literature because trisomy
      14 is associated with early spontaneous abortion. We report a case of a 17-month
      old girl with abnormal skin pigmentation, delayed development, facial
      dysmorphism, and failure to thrive with the 47,XX,+14/46,XX chromosome
      complement.

PMID- 23133488
TI  - Magnetic resonance imaging and spectroscopic analysis in 5 cases of Pelizaeus
      Merzbacher disease: metabolic abnormalities as diagnostic tools.
AB  - Pelizaeus-Merzbacher disease (PMD) is a rare, X-linked recessive disorder
      characterized by dysmyelination in the central nervous system. PMD results from
      deletion, mutation, or duplication of the proteolipid protein gene (PLP1) located
      at Xq22, leading to the failure of axon myelination by oligodendrocytes in the
      central nervous system. PMD may be suspected when there are clinical
      manifestations such as nystagmus, developmental delays, and spasticity, and
      genetic analysis can confirm the diagnosis. Further diagnostic manifestations of
      the disease include a lack of myelination on brain magnetic resonance (MR)
      imaging and aberrant N-acetyl aspartate (NAA) and choline concentrations that
      reflect axonal and myelination abnormalities on phroton MR spectroscopy. We
      report 5 cases of PMD (in 1 girl and 4 boys). PLP1 duplication was detected in 2
      patients. Brain MR analyses and MR spectroscopy were performed for all the
      patients. The brain MR images showed white matter abnormalities typical of PMD,
      and the MR spectroscopic images showed diverse patterns of NAA, creatinine, and
      choline concentrations. We propose that MR spectroscopic analysis of metabolic
      alterations can aid the PMD diagnosis and can contribute to a better
      understanding of the pathogenesis of the disease.

PMID- 23133489
TI  - CD4 T-cell-independent antibody response reduces enterovirus 71 lethality in mice
      by decreasing tissue viral loads.
AB  - Enterovirus 71 (EV71) has induced fatal encephalitis in hundreds of thousands of
      infants and young children in the Asia-Pacific region since the past decade.
      Lymphocyte and antibody responses have been suspected to aggravate EV71-induced
      neurological symptoms, so anti-inflammatory agents have been used to treat
      patients with neurological symptoms. In the present study, we found that mice
      deficient in CD4(+) T cells were resistant to EV71 infection as wild-type mice,
      whereas mice deficient in B cells were highly susceptible to viral infection.
      Compensation of CD4 T-cell function by other immune cells was not likely, because
      wild-type mice depleted of CD4(+) T cells were also resistant to viral infection.
      Infected CD4 T-cell-deficient mice produced virus-specific neutralizing
      antibodies, IgM and IgG. Moreover, adoptive transfer of the virus-specific
      antibody produced by infected CD4 T-cell-deficient mice protected B-cell
      deficient mice from infection by reducing tissue viral loads. Collectively, our
      results show that the CD4 T-cell-independent antibody response promotes the
      survival of EV71-infected mice and suggest great potential for the use of
      vaccines and neutralizing antibodies to reduce fatal symptoms in patients.

PMID- 23133490
TI  - Impact of temozolomide on immune response during malignant glioma chemotherapy.
AB  - Malignant glioma, or glioblastoma, is the most common and lethal form of brain
      tumor with a median survival time of 15 months. The established therapeutic
      regimen includes a tripartite therapy of surgical resection followed by radiation
      and temozolomide (TMZ) chemotherapy, concurrently with radiation and then as an
      adjuvant. TMZ, a DNA alkylating agent, is the most successful antiglioma drug and
      has added several months to the life expectancy of malignant glioma patients.
      However, TMZ is also responsible for inducing lymphopenia and myelosuppression in
      malignant glioma patients undergoing chemotherapy. Although TMZ-induced
      lymphopenia has been attributed to facilitate antitumor vaccination studies by
      inducing passive immune response, in general lymphopenic conditions have been
      associated with poor immune surveillance leading to opportunistic infections in
      glioma patients, as well as disrupting active antiglioma immune response by
      depleting both T and NK cells. Deletion of O6-methylguanine-DNA-methyltransferase
      (MGMT) activity, a DNA repair enzyme, by temozolomide has been determined to be
      the cause of lymphopenia. Drug-resistant mutation of the MGMT protein has been
      shown to render chemoprotection against TMZ. The immune modulating role of TMZ
      during glioma chemotherapy and possible mechanisms to establish a strong TMZ
      resistant immune response have been discussed.

PMID- 23133491
TI  - Effects of Puerariae Radix Extract on Endotoxin Receptors and TNF-alpha
      Expression Induced by Gut-Derived Endotoxin in Chronic Alcoholic Liver Injury.
AB  - Kudzu (Pueraria lobata) is one of the earliest medicinal plants used to treat
      alcohol abuse in traditional Chinese medicine for more than a millennium.
      However, little is known about its effects on chronic alcoholic liver injury.
      Therefore, the present study observed the effects of puerariae radix extract
      (RPE) on chronic alcoholic liver injury as well as Kupffer cells (KCs) activation
      to release tumor necrosis factor alpha (TNF-alpha) induced by gut-derived
      endotoxin in rats and macrophage cell line. RPE was observed to alleviate the
      pathological changes and lipids deposition in liver tissues as well as the serum
      alanine aminotransferase (ALT), aspartate aminotransferase (AST), and hepatic
      gamma-glutamyl transpeptidase (GGT) activity. Meanwhile, RPE inhibited KCs
      activation and subsequent hepatic TNF-alpha expression and downregulated the
      protein expression of endotoxin receptors, lipopolysaccharide binding protein
      (LBP), CD14, Toll-like receptor (TLR) 2, and TLR4 in chronic alcohol intake rats.
      Furthermore, an in vitro study showed that RPE inhibited the expression of TNF
      alpha and endotoxin receptors, CD14 and TLR4, induced by LPS in RAW264.7 cells.
      In summary, this study demonstrated that RPE mitigated liver damage and lipid
      deposition induced by chronic alcohol intake in rats, as well as TNF-alpha
      release, protein expression of endotoxin receptors in vivo or in vitro.

PMID- 23133492
TI  - Traditional medicine in china, Korea, and Japan: a brief introduction and
      comparison.
AB  - Background and Purpose. Traditional medicine (TM) has been widely used in China
      (including the Taiwan region), Korea, and Japan. The purposes of this paper are
      to summarize the basic data on TM systems in these three countries and to compare
      them in terms of overall policy, education, and insurance. Methods. Government
      websites, national statistics, and authoritative papers from each country were
      fully searched. Further data were gathered by TM experts from each country.
      Results. China and Korea showed similar patterns in TM systems, whereas Japan
      showed different patterns. In China and Korea, TM was practiced in a dual system
      with conventional medicine (CM), and TM education was 6-year training programs on
      average for TM doctors, and acupuncture, moxibustion, and cupping were completely
      insured. Whereas, CM was dominant in Japan, and TM was practiced by each health
      care worker who has received different TM education respectively, and main TM
      therapies were partially insured. Conclusions. TM was developed similarly or
      somewhat differently based on differences in cultural background and national
      policies in East Asia. We cautiously propose that this study could contribute to
      the development of TM and also be used for reference in complementary and
      alternative medicine systems.

PMID- 23133493
TI  - Mixture of Polyphenols and Anthocyanins from Vaccinium uliginosum L. Alleviates
      DNCB-Induced Atopic Dermatitis in NC/Nga Mice.
AB  - Vaccinium uliginosum L. (VU) possesses various biological properties, such as
      antioxidant and protective effects against VU-induced skin photoaging. The
      purpose of this study is to evaluate the effects of oral administration of a
      mixture of polyphenols and anthocyanins derived from VU on 2,4
      dinitrochlorobenzene- (DNCB-) induced atopic dermatitis (AD) in NC/Nga mice. We
      assessed anti-AD effects in NC/Nga murine model for a period of 9 weeks. Oral
      administration of the mixture significantly alleviated the AD-like skin symptoms
      and clinical signs including ear thickness and scratching behaviors. Orally
      administrated mixture reduced the level of IgE and IgG1, whereas it increased the
      level of IgG2a in a dose-dependent manner. The calculated IgG1/IgG2a ratio for
      each mouse revealed that the mixture derived from VU also significantly reduced
      the Th2/Th1 ratio, IL-4 and IL-13 (as Th2 cytokines), IFN-gamma, and IL-12 (as a
      Th1 cytokine) in spleens. In addition, it significantly decreased gene
      expression, such as IL-4, IL-5, CCR3, eotaxin-1, IL- 12, IFN-gamma, MCP-1, and IL
      17, in AD-like lesions and suppressed Th17. Histological analyses revealed that
      the epidermis thickness and number of inflammatory cells were significantly
      reduced. In conclusion, oral administration of the mixture in the DNCB-induced AD
      is confirmed to improve AD disease in mice.

PMID- 23133494
TI  - Effects of electroacupuncture of different frequencies on the release profile of
      endogenous opioid peptides in the central nerve system of goats.
AB  - To investigate the release profile of met-enkephalin, beta-endorphin, and
      dynorphin-A in ruminants' CNS, goats were stimulated by electroacupuncture of 0,
      2, 40, 60, 80, or 100 Hz for 30 min. The pain threshold was measured using
      potassium iontophoresis. The peptide levels were determined with SABC
      immunohistochemisty. The results showed that 60 Hz increased pain threshold by
      91%; its increasing rate was higher (P < 0.01) than any other frequency did. 2 Hz
      and 100 Hz increased met-enkephalin immunoactivities (P < 0.05) in nucleus
      accumbens, septal area, caudate nucleus, amygdala, paraventricular nucleus of
      hypothalamus, periaqueductal gray, dorsal raphe nucleus, and locus ceruleus. The
      two frequencies elicited beta-endorphin release (P < 0.05) in nucleus accumbens,
      septal area, supraoptic nucleus, ventromedial nucleus of hypothalamus,
      periaqueductal gray, dorsal raphe nucleus, locus ceruleus, solitary nucleus and
      amygdala. 60 Hz increased (P < 0.05) met-enkephalin or beta-endorphin
      immunoactivities in the nuclei and areas mentioned above, and habenular nucleus,
      substantia nigra, parabrachial nucleus, and nucleus raphe magnus. High
      frequencies increased dynorphin-A release (P < 0.05) in spinal cord dorsal horn
      and most analgesia-related nuclei. It suggested that 60 Hz induced the
      simultaneous release of the three peptides in extensive analgesia-related nuclei
      and areas of the CNS, which may be contributive to optimal analgesic effects and
      species variation.

PMID- 23133495
TI  - Red ginseng extract attenuates kainate-induced excitotoxicity by antioxidative
      effects.
AB  - This study investigated the neuroprotective activity of red ginseng extract (RGE,
      Panax ginseng, C. A. Meyer) against kainic acid- (KA-) induced excitotoxicity in
      vitro and in vivo. In hippocampal cells, RGE inhibited KA-induced excitotoxicity
      in a dose-dependent manner as measured by the MTT assay. To study the possible
      mechanisms of the RGE-mediated neuroprotective effect against KA-induced
      cytotoxicity, we examined the levels of intracellular reactive oxygen species
      (ROS) and [Ca(2+)](i) in cultured hippocampal neurons and found that RGE
      treatment dose-dependently inhibited intracellular ROS and [Ca(2+)](i) elevation.
      Oral administration of RGE (30 and 200 mg/kg) in mice decreased the
      malondialdehyde (MDA) level induced by KA injection (30 mg/kg, i.p.). In
      addition, similar results were obtained after pretreatment with the radical
      scavengers Trolox and N, N'-dimethylthiourea (DMTU). Finally, after confirming
      the protective effect of RGE on hippocampal brain-derived neurotropic factor
      (BDNF) protein levels, we found that RGE is active compounds mixture in KA
      induced hippocampal mossy-fiber function improvement. Furthermore, RGE eliminated
      1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, and the IC(50) was approximately
      10 mg/ml. The reductive activity of RGE, as measured by reaction with hydroxyl
      radical ((*)OH), was similar to trolox. The second-order rate constant of RGE for
      (*)OH was 3.5-4.5 * 10(9) M(-1).S(-1). Therefore, these results indicate that RGE
      possesses radical reduction activity and alleviates KA-induced excitotoxicity by
      quenching ROS in hippocampal neurons.

PMID- 23133496
TI  - Fermented mistletoe extract as a multimodal antitumoral agent in gliomas.
AB  - In Europe, commercially available extracts from the white-berry mistletoe (Viscum
      album L.) are widely used as a complementary cancer therapy. Mistletoe lectins
      have been identified as main active components and exhibit cytotoxic effects as
      well as immunomodulatory activity. Since it is still not elucidated in detail how
      mistle toe extracts such as ISCADOR communicate their effects, we analyzed the
      mechanisms that might be responsible for their antitumoral function on a
      molecular and functional level. ISCADOR-treated glioblastoma (GBM) cells down
      regulate central genes involved in glioblastoma progression and malignancy such
      as the cytokine TGF-beta and matrix-metalloproteinases. Using in vitro
      glioblastoma/immune cell co-cultivation assays as well as measurement of cell
      migration and invasion, we could demonstrate that in glioblastoma cells, lectin
      rich ISCADOR M and ISCADOR Q significantly enforce NK-cell-mediated GBM cell
      lysis. Beside its immune stimulatory effect, ISCADOR reduces the migratory and
      invasive potential of glioblastoma cells. In a syngeneic as well as in a
      xenograft glioblastoma mouse model, both pretreatment of tumor cells and
      intratumoral therapy of subcutaneously growing glioblastoma cells with ISCADOR Q
      showed delayed tumor growth. In conclusion, ISCADOR Q, showing multiple positive
      effects in the treatment of glioblastoma, may be a candidate for concomitant
      treatment of this cancer.

PMID- 23133497
TI  - Patch clamp: a powerful technique for studying the mechanism of acupuncture.
AB  - Cellular and molecular events can be investigated using electrophysiological
      techniques. In particular, the patch-clamp method provides detailed information.
      In addition, the patch-clamp technique has become a powerful method for
      investigating the mechanisms underlying the effects of acupuncture. In this
      paper, recent researches on how acupuncture might modulate electrophysiological
      responses in the central nervous system (CNS) and affect peripheral structures
      are reviewed.

PMID- 23133498
TI  - Effects of berberine and hwangryunhaedok-tang on oral bioavailability and
      pharmacokinetics of ciprofloxacin in rats.
AB  - Hwangryunhaedok-Tang (HR) and berberine-containing single herbs are used to treat
      bacterial infection and inflammatory diseases in eastern Asia. The combination of
      berberine-containing herbal medicines and ciprofloxacin can be an excellent
      antibacterial chemotherapy against multidrug resistance bacteria. To evaluate the
      pretreatment effect of berberine and HR, vehicle, berberine (25 and 50
      mg/kg/day), and HR (1.4 g/kg/day) were daily administered to rats for five
      consecutive days. On day 6, ciprofloxacin was administered (10 mg/kg, i.v. and 20
      mg/kg, p.o.) to rats. To assess cotreatment effect of berberine and
      ciprofloxacin, berberine (50 mg/kg) and ciprofloxacin (20 mg/kg) were
      coadministered by single oral gavage. Pharmacokinetic data were estimated by
      noncompartmental model. Compared with ciprofloxacin alone (control group),
      coadministration of berberine (50 mg/kg) and ciprofloxacin significantly
      decreased C(max) of ciprofloxacin (P < 0.05). In addition, the pretreatment of
      berberine (50 mg/kg/day) and HR (1.4 g/kg/day) significantly decreased C(max) and
      AUC(0->infinity), compared with control group (P < 0.05). The oral
      bioavailability of ciprofloxacin was reduced by cotreatment of berberine and
      pretreatment of berberine and HR. Our results suggest that the expression of P
      glycoprotein and organic anion and/or organic cation transporters (OAT/OCT) could
      take a role in reduced oral bioavailability of ciprofloxacin by berberine and HR.

PMID- 23133499
TI  - Results of a 2-week inpatient stay at the department for internal and integrative
      medicine: an observational study.
AB  - Introduction. The Department for Internal and Integrative Medicine in Essen
      utilizes mind/body medical elements in order to empower patients with chronic
      diseases to better cope with their symptoms and to adopt a healthy lifestyle.
      This study explored the influence and predictors of a 2-week integrative
      treatment program on patients' quality of life. Methods. This observational study
      was conducted with inpatients as part of the quality assurance program. Patients'
      quality of life, psychological symptoms, and health locus of control were
      measured on admission and discharge and again 3, 6, and 12 months after
      discharge. Regression analyses were conducted to determine the factors predicting
      improved quality of life. Results. Data from 2486 inpatients treated in 2001-2004
      were included (80% female, mean age 53.9 +/- 14.3 years). Response rates
      decreased to 50% at 12 months. Small-to-moderate effects were found on patients'
      quality of life, anxiety, and depression. Patients' internal locus of control
      significantly increased. Improved quality of life was mainly predicted by lower
      baseline scores. Conclusion. Results of this study suggest that a 2-week
      inpatient treatment might sustainably reduce patients' symptoms and increase
      their quality of life; however, conclusions are only preliminary. More research
      is needed to enable the effectiveness to be judged conclusively.

PMID- 23133500
TI  - The impact of sociodemographic factors on the utilisation of support services for
      family caregivers of elderly dependents - results from the German sample of the
      EUROFAMCARE study.
AB  - OBJECTIVES: As in nearly all European countries, demographic developments in
      Germany have led to both a relative and an absolute increase in the country's
      elderly population. The care and support needed by these people is primarily
      provided by relatives or friends and close acquaintances within the home
      environment. The major challenges for society are to sustain, promote and support
      these informal resources. In order to achieve this, it is crucial that family
      caregivers are provided with situation-specific services that support them and
      relieve their burden of care. The major challenges for society are therefore to
      sustain, promote and support informal resources and to provide the opportunity
      for the use of services aimed at assisting and relieving the burden of family
      caregivers. METHODS: In the context of the EUROFAMCARE study, 1,003 family
      caregivers from Germany were interviewed at home about their experiences using a
      standardized questionnaire. Included in the study were primary caregivers
      providing at least four hours of personal care or support per week to a relative
      aged 65 years or older. Subjects solely providing financial support were
      excluded. In this paper, a linear regression analysis has been conducted to
      analyse impact of sociodemographic factors on the utilisation of support
      services. RESULTS: The family caregivers were 54 years on average (SD=13.4), 76%
      of them were female. The dependent elderly were 80 years on average (SD=8.3), and
      69% of them were women. 60% of them were receiving long-term care insurance
      benefits. Use of support services aimed directly at family caregivers is very
      low. After including certain services aimed primarily at those in need of care
      but also often serving as a source of relief for family caregivers, the
      percentage of caregivers using support services increased slightly. Among
      sociodemographic characteristics, caregivers' gender and education level have the
      greatest influence on services use. Other influential factors are caregivers'
      perception of their caregiving burden and their assessment of the dependent
      family member's need for assistance and support.

PMID- 23133501
TI  - The influence of social determinants on the use of prevention and health
      promotion services: Results of a systematic literature review.
AB  - BACKGROUND: The following analysis aims to determine whether differences in the
      use of prevention and health promotion services in Germany can be attributed to
      health inequality between different social status groups measured by education,
      occupation and income and where certain improvements can be made in health
      promotion and prevention efforts and research to reduce those differences.
      METHODS: A systematic literature search was conducted using MedPilot to identify
      relevant articles published between 1998 and 2010 in the Medline, Medizinische
      Gesundheit, CC Med, Deutsches Arzteblatt and Sozialmedizin (SOMED) databases, the
      Hogrefe, Karger, Krause and Pachermegg and Thieme publisher databases, the
      Cochrane Database of Systematic Reviews (CDSR), the Cochrane Database of
      Abstracts of Reviews of Effectiveness (DARE), and the Cochrane Central Register
      of Controlled Trials. RESULTS: A total of 23 empirical studies on the topic of
      "prevention, health prevention and social inequality" met the criteria for
      inclusion in the review. 20 of the 23 reviewed studies provided relatively clear
      evidence of a significant association between higher social status and greater
      use of prevention and health promotion services. According to the reviewed
      studies, gender tends to have a greater effect on the use of prevention and
      health promotion services than characteristics of vertical social inequality. No
      studies were found dealing with tertiary prevention or using qualitative methods
      to explore their research questions. CONCLUSIONS: Overall, the review shows that
      there is sufficient evidence for the relationship between social status and the
      use of prevention and health promotion services and that this association is both
      significant and relevant. There are, however, a few "blind spots" in research on
      this topic, such as a lack of studies on tertiary prevention, especially with
      regards to prevention and health promotion services use among men, as well as
      general studies on health promotion among men and women. There is also a lack of
      published intervention studies demonstrating how to better reach the socially
      disadvantaged.

PMID- 23133502
TI  - Utilisation of rheumatology care services in Germany: the case of physical
      therapy and self-help groups.
AB  - Physical Therapy (PT) and self-help groups (SHG) are important components of
      health care in rheumatic diseases. The utilisation of PT and SHG by patients with
      rheumatic diseases may be influenced by several factors. The aim of this study is
      to summarize the evidence on PT and SHG utilisation of patients with rheumatic
      diseases in Germany. We systematically searched the MEDLINE-database for studies
      that evaluated the utilisation and factors that possibly influence the
      utilisation of PT and SHG. Eight studies were found for PT-utilisation and one
      for SHG-utilisation. Between 25 and 59 percent of patients with rheumatic
      diseases received PT services. Several individual and contextual factors that may
      influence the utilisation could be identified. In conclusion, evidence exists for
      wide variations in the utilisation of PT services and an underuse of such
      services among patients with rheumatic diseases in Germany. By contrast, little
      evidence exists on the utilisation of SHG.

PMID- 23133503
TI  - Body weight changes and outpatient medical care utilisation: Results of the
      MONICA/KORA cohorts S3/F3 and S4/F4.
AB  - OBJECTIVES: To test the effects of body weight maintenance, gain, and loss on
      health care utilisation in terms of outpatient visits to different kinds of
      physicians in the general adult population. METHODS: Self-reported utilisation
      data were collected within two population-based cohorts (baseline surveys: MONICA
      S3 1994/95 and KORA-S4 1999/2001; follow-ups: KORA-F3 2004/05 and KORA-F4
      2006/08) in the region of Augsburg, Germany, and were pooled for present
      purposes. N=5,147 adults (complete cases) aged 25 to 64 years at baseline
      participated. Number of visits to general practitioners (GPs), internists, and
      other specialists as well as the total number of physician visits at follow-up
      were compared across 10 groups defined by body mass index (BMI) category
      maintenance or change. Body weight and height were measured anthropometrically.
      Hierarchical generalized linear regression analyses with negative binomial
      distribution adjusted for sex, age, socioeconomic status (SES), survey, and the
      need factors incident diabetes and first cancer between baseline and follow-up
      were conducted. RESULTS: In fully adjusted models, compared to the group of
      participants that maintained normal weight from baseline to follow-up, the
      following groups had significantly higher GP utilisation rates: weight gain from
      normal weight (+36%), weight loss from preobesity (+39%), maintained preobesity
      (+34%), weight gain after preobesity (+43%), maintained moderate obesity (+48%),
      weight gain from moderate obesity (+107%), weight loss from severe obesity
      (+114%), and maintained severe obesity (+83%). Regarding internists, those
      maintaining moderate obesity reported +107% more visits; those with weight gain
      from moderate obesity reported +91%. The latter group also had +41% more
      consultations with other physicians. Across all physicians, mean number of visits
      were estimated at 7.8 per year for maintained normal weight, 9 for maintained
      preobesity, 11 for maintained moderate obesity, and 12 for maintained severe
      obesity. Among those with weight loss, the mean number of visits were 8.7, 10.6
      and 10.8 for baseline preobesity, moderate obesity, and severe obesity,
      respectively. Finally, those with weight gain from normal weight and preobesity
      reported 9.4 and 9.3 visits, respectively, and those with baseline moderate and
      follow-up severe obesity reported 13.1 visits (the most overall). Women reported
      higher GP and other physician utilisation. While all utilisation rates increased
      with age, GP utilisation was lower in middle to high SES groups. CONCLUSION:
      Compared to maintained normal weight over a 7- to 10-year period, maintained
      overweight, weight gain and weight loss are associated with higher outpatient
      physician utilisation in adults, especially after baseline obesity. These effects
      only partly became insignificant after inclusion of incident diabetes or first
      cancer into the model. Future research should further elucidate the associations
      between weight development and health care utilisation by BMI status and the
      mechanisms underlying these associations.

PMID- 23133504
TI  - The prevalence of medical services use. How comparable are the results of large
      scale population surveys in Germany?
AB  - BACKGROUND: The large-scale representative population surveys conducted by
      Germany's Robert Koch Institute (RKI) contain questions pertaining to health and
      its determinants as well as the prevalence and frequency of outpatient services
      utilization. The same holds for the Socioeconomic Panel (SOEP, Sozio-okonomisches
      Panel) and the Bertelsmann Healthcare Monitor (Gesundheitsmonitor) surveys. The
      purpose of this study is to examine the comparability of the instruments used in
      these surveys and their results. METHODS: The questions on outpatient care
      utilization examined in this study were taken from the public use files of the
      East-West Health Survey (Ost-West Survey; OW1991), the 1998 Federal National
      Health Survey (Bundesgesundheitssurvey; BGS1998), the 2003 Telephone Health
      Survey (TEL2003), and the 2009 German Health Update (Gesundheit in Deutschland
      aktuell GEDA2009). The study also used data from the 26 waves of the SOEP (1984
      2009) and the 16 waves of the Bertelsmann Healthcare Monitor (2001-2009) studies.
      RESULTS: In the OW1991 and the BGS1998, questions on outpatient services
      utilization differ by the types of physicians inquired about. The four-week
      prevalence of contact with general practitioneers (GP) was 29% in the OW1991; the
      twelve-month prevalence in the BGS1998 was 69%. The OW1991 and the BGS1998 also
      surveyed participants on the number of physician contacts made during those
      reference periods (average number of contacts: 1.8 over the previous four weeks
      (OW1991) and 4.9 over the previous 12 months (BGS1998)). The TEL2003 inquires
      into the three-month prevalence of contact with private practice physicians in
      general (63%) as well as the number of contacts with primary care physicians over
      the previous twelve months (88% with at least one contact, average number of
      contacts: 4.6, range: 1-92). In the GEDA2009 survey, 88% of participants reported
      having contacted a physician at least once over the previous twelve months and an
      average of 6.1 contacts with all physicians working under contract with the
      German statutory health insurance (SHI) funds. The 2009 SOEP survey revealed a
      28% three-month prevalence of contact with all types of physicians and an average
      of 3.6 contacts (among participants who had made at least one contact during this
      period). According to the Bertelsmann Health Monitor, the twelve-month prevalence
      of contact with GPs was 82%, with the average number of contacts being 5.0. The
      Bertelsmann Health Monitor also surveys participants on contacts made with four
      other types of physicians; the OW1991 and the BGS1998 ask about contacts made
      with over ten different types of physicians when examining the frequency of
      services use. CONCLUSIONS: Not only do the target groups of the RKI surveys, the
      SOEP and the Bertelsmann Health Monitor differ; their questions on outpatient
      care utilization also differ in terms of examined reference period and types of
      physicians contacted by survey participants, question wording including
      clarifications (e.g., asking the participant to also consider contacts not made
      "in person" with physicians when answering a question), and response categories.
      Therefore, unlike the results of the surveys' questions on inpatient care, the
      results of questions on the use of outpatient care services are not easily
      comparable, even those regarding contact with primary care physicians and GPs.
      The results of secondary analyses of German SHI claims data could be used to
      confirm the external validity of the surveys' results.

PMID- 23133505
TI  - Re-revisiting Andersen's Behavioral Model of Health Services Use: a systematic
      review of studies from 1998-2011.
AB  - OBJECTIVE: This systematic review aims to assess the use and implementation of
      the Behavioral Model of Health Services Use developed by Ronald M. Andersen in
      recent studies explicity using this model. METHODS: A systematic search was
      conducted using PubMed in April 2011. The search strategy aimed to identify all
      articles in which the Andersen model had been applied and which had been
      published between 1998 and March 2011 in English or German. The search yielded a
      total of 328 articles. Two researchers independently reviewed the retrieved
      articles for possible inclusion using a three-step selection process (1.
      title/author, 2. abstract, 3. full text) with pre-defined inclusion and exclusion
      criteria for each step. 16 studies met all of the inclusion criteria and were
      used for analysis. A data extraction form was developed to collect information
      from articles on 17 categories including author, title, population description,
      aim of the study, methodological approach, use of the Andersen model, applied
      model version, and main results. The data collected were collated into six main
      categories and are presented accordingly. RESULTS: Andersen's Behavioral Model
      (BM) has been used extensively in studies investigating the use of health
      services. The studies identified for this review showed that the model has been
      used in several areas of the health care system and in relation to very different
      diseases. The 1995 version of the BM was the version most frequently applied in
      the studies. However, the studies showed substantial differences in the variables
      used. The majority of the reviewed studies included age (N=15), marital status
      (N=13), gender/sex (N=12), education (N=11), and ethnicity (N=10) as predisposing
      factors and income/financial situation (N=10), health insurance (N=9), and having
      a usual source of care/family doctor (N=9) as enabling factors. As need factors,
      most of the studies included evaluated health status (N=13) and self
      reported/perceived health (N=9) as well as a very wide variety of diseases.
      Although associations were found between the main factors examined in the studies
      and the utilization of health care, there was a lack of consistency in these
      findings. The context of the studies reviewed and the characteristics of the
      study populations seemed to have a strong impact on the existence, strength and
      direction of these associations. CONCLUSIONS: Although the frequently used BM was
      explicitly employed as the theoretical background for the reviewed studies, their
      operationalizations of the model revealed that only a small common set of
      variables was used and that there were huge variations in the way these variables
      were categorized, especially as it concerns predisposing and enabling factors.
      This may stem from the secondary data sets used in the majority of the studies,
      which limited the variables available for study. Primary studies are urgently
      needed to enrich our understanding of health care utilization and the complexity
      of the processes shown in the BM.

PMID- 23133506
TI  - Health care utilization in Germany: The NWIn research network.

PMID- 23133508
TI  - Postlingual hearing loss as a mitochondrial 3243A>G mutation phenotype.
AB  - BACKGROUND: The prevalence of isolated hearing loss (HL) associated with the
      m.3243A>G mutation is unknown. The aim of this study was to assess the frequency
      and heteroplasmy level of the m.3243A>G mutation in a large group of Polish
      patients with postlingual bilateral sensorineural HL of unidentified cause.
      METHODOLOGY/PRINCIPAL FINDINGS: A molecular search was undertaken in the archival
      blood DNA of 1482 unrelated patients with isolated HL that had begun at ages
      between 5 and 40 years. Maternal relatives of the probands were subsequently
      investigated and all carriers underwent audiological tests. The m.3243A>G
      mutation was found in 16 of 1482 probands (an incidence of 1.08%) and 18 family
      members. Of these 34 individuals, hearing impairment was detected in 29 patients
      and the mean onset of HL was at 26 years. Some 42% of the identified m.3243A>G
      carriers did not develop multisystem symptomatology over the following 10 years.
      Mean heteroplasmy level of m.3243A>G was lowest in blood at a level of 14% and
      highest in urine at 58%. These values were independent of the manifested clinical
      severity of the disease. CONCLUSIONS: A single m.3243A>G carrier can usually be
      found among each 100 individuals who have postlingual hearing loss of unknown
      cause. Urine samples are best for detecting the m.3243A>G mutation and diagnosing
      mitochondrially inherited hearing loss.

PMID- 23133509
TI  - An analysis of diet quality, how it controls fatty acid profiles, isotope
      signatures and stoichiometry in the malaria mosquito Anopheles arabiensis.
AB  - BACKGROUND: Knowing the underlying mechanisms of mosquito ecology will ensure
      effective vector management and contribute to the overall goal of malaria
      control. Mosquito populations show a high degree of population plasticity in
      response to environmental variability. However, the principle factors controlling
      population size and fecundity are for the most part unknown. Larval habitat and
      diet play a crucial role in subsequent mosquito fitness. Developing the most
      competitive insects for sterile insect technique programmes requires a
      "production" orientated perspective, to deduce the most effective larval diet
      formulation; the information gained from this process offers us some insight into
      the mechanisms and processes taking place in natural native mosquito habitats.
      METHODOLOGY/PRINCIPAL FINDINGS: Fatty acid profiles and de-novo or direct
      assimilation pathways, of whole-individual mosquitoes reared on a range of larval
      diets were determined using pyrolysis gas chromatograph/mass spectrometry. We
      used elemental analysis and isotope ratio mass spectrometry to measure individual
      whole-body carbon, nitrogen and phosphorous values and to assess the impact of
      dietary quality on subsequent population stoichiometry, size, quality and
      isotopic signature. Diet had the greatest impact on fatty acid (FA) profiles of
      the mosquitoes, which exhibited a high degree of dietary routing, characteristic
      of generalist feeders. De-novo synthesis of a number of important FAs was
      observed. Mosquito C:N stoichiometry was fixed in the teneral stage. Dietary N
      content had significant influence on mosquito size, and P was shown to be a
      flexible pool which limited overall population size. CONCLUSIONS/SIGNIFICANCE:
      Direct routing of FAs was evident but there was ubiquitous de-novo synthesis
      suggesting mosquito larvae are competent generalist feeders capable of survival
      on diet with varying characteristics. It was concluded that nitrogen availability
      in the larval diet controlled teneral mosquito size and that teneral CN ratio is
      a sex- and species-specific fixed parameter. This finding has significant
      implications for overall mosquito competitiveness and environmental management.

PMID- 23133510
TI  - Temperament traits and chronic pain: the association of harm avoidance and pain
      related anxiety.
AB  - OBJECTIVE: Anxiety symptoms are common in chronic pain patients. High levels of
      anxiety are associated with increased pain experience and disability. Proneness
      to anxiety has a large interindividual variation. The aim of the study was to
      determine whether the anxiety-related temperament trait Harm Avoidance (HA), is
      associated with pain-related anxiety. METHODS: One hundred chronic pain patients
      in a multidisciplinary pain clinic participated in the study. The patients were
      assessed using the HA scale of the Temperament and Character Inventory (TCI) of
      Cloninger and Pain Anxiety Symptoms Scale-20 (PASS-20). Both the HA total score
      and the four subscales of HA were analyzed. Current pain intensity was measured
      using the Visual Analogue Scale (VAS). The Beck Depression Inventory (BDI) was
      used to control for the influence of depression on the personality measurement.
      RESULTS: The HA total score was associated with PASS-20, but the association
      became non-significant after controlling for depression. The HA4 Fatigability
      subscale was associated with the PASS scales. Depression did not influence this
      association. Pain intensity was not correlated with HA or the PASS scales.
      However, the association between HA4 Fatigability and PASS was influenced by pain
      intensity. Higher pain intensity was associated with stronger association between
      the scales. CONCLUSION: Harm Avoidance, representing temperament and trait
      related anxiety, has relevance in pain-related anxiety. Assessing personality and
      temperament may deepen the clinician's understanding of the pain experience and
      behavior in chronic pain patients.

PMID- 23133511
TI  - An odor timer in milk? Synchrony in the odor of milk effluvium and neonatal
      chemosensation in the mouse.
AB  - Mammalian newborns exhibit avid responsiveness to odor compounds emanating from
      conspecific milk. Milk is however developmentally heterogeneous in composition as
      a function of both evolved constraints and offspring demand. The present study
      aimed to verify whether milk odor attractivity for neonates is equally
      distributed along lactation in Mus musculus (Balb-c strain). Therefore, we
      exposed pups varying in age to milk samples collected from females in different
      lactational stages. The pups were assayed at postnatal days 2 (P2), 6 (P6) and 15
      (P15) in a series of paired-choice tests opposing either murine milk and a blank
      (water), or two samples of milk collected in different stages of lactation
      [lactation days 2 (L2), 6 (L6), and 15 L15)]. Pups of any age were able to
      detect, and were attracted to, the odor of the different milk. When milk from
      different lactational stages were simultaneously presented, P2 pups oriented for
      a similar duration to the odors of L2 and of L6 milk, but significantly less to
      the odor of L15 milk. Next, P6 pups roamed equivalently over L2 and L6 milk
      odors, but still less over the odor of L15 milk. Finally, P15 pups explored as
      much L15 milk odor as the odors of both L2 and L6 milk. This developmental shift
      in milk attractivity is discussed in terms of changing chemosensory properties of
      milk and of shifting chemosensory abilities/experience of pups.

PMID- 23133512
TI  - A transcriptome-wide screen for mRNAs enriched in fetal Leydig cells: CRHR1
      agonism stimulates rat and mouse fetal testis steroidogenesis.
AB  - Fetal testis steroidogenesis plays an important role in the reproductive
      development of the male fetus. While regulators of certain aspects of
      steroidogenesis are known, the initial driver of steroidogenesis in the human and
      rodent fetal testis is unclear. Through comparative analysis of rodent fetal
      testis microarray datasets, 54 candidate fetal Leydig cell-specific genes were
      identified. Fetal mouse testis interstitial expression of a subset of these genes
      with unknown expression (Crhr1, Gramd1b, Itih5, Vgll3, and Vsnl1) was verified by
      whole-mount in situ hybridization. Among the candidate fetal Leydig cell-specific
      factors, three receptors (CRHR1, PRLR, and PROKR2) were tested for a
      steroidogenic function using ex vivo fetal testes treated with receptor agonists
      (CRH, PRL, and PROK2). While PRL and PROK2 had no effect, CRH, at low
      (approximately 1 to 10) nM concentration, increased expression of the
      steroidogenic genes Cyp11a1, Cyp17a1, Scarb1, and Star in GD15 mouse and GD17 rat
      testes, and in conjunction, testosterone production was increased. Exposure of
      GD15 fetal mouse testis to a specific CRHR1 antagonist blunted the CRH-induced
      steroidogenic gene expression and testosterone responses. Similar to ex vivo
      rodent fetal testes, >= 10 nM CRH exposure of MA-10 Leydig cells increased
      steroidogenic pathway mRNA and progesterone levels, showing CRH can enhance
      steroidogenesis by directly targeting Leydig cells. Crh mRNA expression was
      observed in rodent fetal hypothalamus, and CRH peptide was detected in rodent
      amniotic fluid. Together, these data provide a resource for discovering factors
      controlling fetal Leydig cell biology and suggest that CRHR1 activation by CRH
      stimulates rat and mouse fetal Leydig cell steroidogenesis in vivo.

PMID- 23133513
TI  - Dissecting systemic RNA interference in the red flour beetle Tribolium castaneum:
      parameters affecting the efficiency of RNAi.
AB  - The phenomenon of RNAi, in which the introduction of dsRNA into a cell triggers
      the destruction of the corresponding mRNA resulting in a gene silencing effect,
      is conserved across a wide array of plant and animal phyla. However, the
      mechanism by which the dsRNA enters a cell, allowing the RNAi effect to occur
      throughout a multicellular organism (systemic RNAi), has only been studied
      extensively in certain plants and the nematode Caenorhabditis elegans. In recent
      years, RNAi has become a popular reverse genetic technique for gene silencing in
      many organisms. Although many RNAi techniques in non-traditional model organisms
      rely on the systemic nature of RNAi, little has been done to analyze the
      parameters required to obtain a robust systemic RNAi response. The data provided
      here show that the concentration and length of dsRNA have profound effects on the
      efficacy of the RNAi response both in regard to initial efficiency and duration
      of the effect in Tribolium castaneum. In addition, our analyses using a series of
      short dsRNAs and chimeric dsRNA provide evidence that dsRNA cellular uptake (and
      not the RNAi response itself) is the major step affected by dsRNA size in
      Tribolium. We also demonstrate that competitive inhibition of dsRNA can occur
      when multiple dsRNAs are injected together, influencing the effectiveness of
      RNAi. These data provide specific information essential to the design and
      implementation of RNAi based studies, and may provide insight into the molecular
      basis of the systemic RNAi response in insects.

PMID- 23133514
TI  - Analysis of an ordered, comprehensive STM mutant library in infectious Borrelia
      burgdorferi: insights into the genes required for mouse infectivity.
AB  - The identification of genes important in the pathogenesis of Lyme disease
      Borrelia has been hampered by exceedingly low transformation rates in low
      passage, infectious organisms. Using the infectious, moderately transformable B.
      burgdorferi derivative 5A18NP1 and signature-tagged versions of the Himar1
      transposon vector pGKT, we have constructed a defined transposon library for the
      efficient genome-wide investigation of genes required for wild-type pathogenesis,
      in vitro growth, physiology, morphology, and plasmid replication. To facilitate
      analysis, the insertion sites of 4,479 transposon mutants were determined by
      sequencing. The transposon insertions were widely distributed across the entire
      B. burgdorferi genome, with an average of 2.68 unique insertion sites per kb DNA.
      The 10 linear plasmids and 9 circular plasmids had insertions in 33 to 100
      percent of their predicted genes. In contrast, only 35% of genes in the 910 kb
      linear chromosome had incapacitating insertions; therefore, the remaining 601
      chromosomal genes may represent essential gene candidates. In initial signature
      tagged mutagenesis (STM) analyses, 434 mutants were examined at multiple tissue
      sites for infectivity in mice using a semi-quantitative, Luminex-based DNA
      detection method. Examples of genes found to be important in mouse infectivity
      included those involved in motility, chemotaxis, the phosphoenolpyruvate
      phosphotransferase system, and other transporters, as well as putative plasmid
      maintenance genes. Availability of this ordered STM library and a high-throughput
      screening method is expected to lead to efficient assessment of the roles of B.
      burgdorferi genes in the infectious cycle and pathogenesis of Lyme disease.

PMID- 23133515
TI  - Safety of cell therapy with mesenchymal stromal cells (SafeCell): a systematic
      review and meta-analysis of clinical trials.
AB  - BACKGROUND: Mesenchymal stromal cells (MSCs, "adult stem cells") have been widely
      used experimentally in a variety of clinical contexts. There is interest in using
      these cells in critical illness, however, the safety profile of these cells is
      not well known. We thus conducted a systematic review of clinical trials that
      examined the use MSCs to evaluate their safety. METHODS AND FINDINGS: MEDLINE,
      EMBASE, and the Cochrane Central Register of Controlled Trials (to June 2011),
      were searched. Prospective clinical trials that used intravascular delivery of
      MSCs (intravenously or intra-arterially) in adult populations or mixed adult and
      pediatric populations were identified. Studies using differentiated MSCs or
      additional cell types were excluded. The primary outcome adverse events were
      grouped according to immediate events (acute infusional toxicity, fever), organ
      system complications, infection, and longer term adverse events (death,
      malignancy). 2347 citations were reviewed and 36 studies met inclusion criteria.
      A total of 1012 participants with clinical conditions of ischemic stroke, Crohn's
      disease, cardiomyopathy, myocardial infarction, graft versus host disease, and
      healthy volunteers were included. Eight studies were randomized control trials
      (RCTs) and enrolled 321 participants. Meta-analysis of the RCTs did not detect an
      association between acute infusional toxicity, organ system complications,
      infection, death or malignancy. There was a significant association between MSCs
      and transient fever. CONCLUSIONS: Based on the current clinical trials, MSC
      therapy appears safe. However, further larger scale controlled clinical trials
      with rigorous reporting of adverse events are required to further define the
      safety profile of MSCs.

PMID- 23133516
TI  - Molecular cloning, expression and molecular modeling of chemosensory protein from
      Spodoptera litura and its binding properties with Rhodojaponin III.
AB  - Insects stimulate specific behaviors by the correct recognition of the chemicals
      in the external environment. Rhodojaponin III is a botanical grayanoid diterpenid
      oviposition deterrent isolated from Rhododendron molle. In this study we aimed to
      determine whether the CSPs involved in the recognition of Rhodojaponin III. A
      full-length cDNA encoding chemosensory protein was isolated from the antennae of
      Spodoptera litura Fabricius (CSPSlit, GenBank Accession No. DQ007458). The full
      length cDNA of NlFoxA is 1789 bp and has an open reading frame (ORF) of 473 bp,
      encoding a protein of 126 amino acids, Northern blot analysis revealed that
      CSPSlit mRNA was mainly expressed in the antennae, legs, wings and female
      abdomens. A three-dimensional model of CSPSlit was constructed using homology
      modeling method, and its reliability was evaluated. The active site of CSPSlit
      was calculated using CDOCKER program indicated that the Tyr24, Ile45, Leu49,
      Thr64, Leu68, Trp79 and Leu82 were responsible ligand-binding active site on
      identifying Rhodojaponin III in the CSPSlit. The recombinant CSPSlit protein was
      expressed in Escherichia coli and purified using single-step Ni-NTA affinity
      chromatography. Fluorescence emission spectra revealed that the CSPSlit protein
      had significant affinity to rhodojaponin III. These results mean that CSPSlit is
      critical for insects identify the Rhodojaponin III.

PMID- 23133517
TI  - Influence of pericarp, cotyledon and inhibitory substances on sharp tooth oak
      (Quercus aliena var. acuteserrata) germination.
AB  - In order to explore the mechanism of delayed and uneven germination in sharp
      tooth oak (Quercus aliena var. acuteserrata) (STO), mechanical scarification
      techniques were used to study STO root and shoot germination and growth. The
      techniques used were: removing cup scar (RS), removing the pericarp (RP), and
      cutting off 1/2 (HC) and 2/3 (TC) cotyledons. Germination percentage and root and
      shoot length for Chinese cabbage (Beassica pekinensis) seeds (CCS) were also
      investigated for CCS cultivated in a Sanyo growth cabinet watered by distilled
      water and 80% methanol extracts from the acorn embryo, cotyledon and pericarp
      with concentrations of 1.0 g, 0.8 g, 0.6 g and 0.4 g dry acorn weight per ml
      methanol. The results showed that the majority of roots and shoots from acorns
      with RP and HC treatment emerged two weeks earlier, more simultaneously, and
      their total emergencies were more than 46% and 28% higher, respectively. TC
      accelerated root and shoot emergence time and root length, but root and shoot
      germination rate and shoot height had no significant difference from the control.
      Positive consequences were not observed on all indices of RS treatment. The
      germination rates of CCS watered by 1.0 g . ml(-1) methanol extracts from the
      embryo and cotyledon were significantly lower than those from the pericarp, and
      all concentrations resulted in decreased growth of root and shoot. Methanol
      extracts from pericarp significantly reduced root length of CCS, but presented
      little response in germination percentage and shoot length. The inhibitory effect
      was gradually increased with the increasing concentration of the methanol
      extract. We conclude that both the mechanical restriction of the pericarp and the
      presence of germination inhibitors in the embryo, cotyledon and pericarp are the
      causes for delayed and asynchronous germination of STO acorns.

PMID- 23133518
TI  - Reproducibility of structural, resting-state BOLD and DTI data between identical
      scanners.
AB  - Increasingly, clinical trials based on brain imaging are adopting multiple
      sites/centers to increase their subject pool and to expedite the studies, and
      more longitudinal studies are using multiple imaging methods to assess structural
      and functional changes. Careful investigation of the test-retest reliability and
      image quality of inter- or intra- scanner neuroimaging measurements are critical
      in the design, statistical analysis and interpretation of results. We propose a
      framework and specific metrics to quantify the reproducibility and image quality
      for neuroimaging studies (structural, BOLD and Diffusion Tensor Imaging)
      collected across identical scanners and following a major hardware repair
      (gradient coil replacement). We achieved consistent measures for the proposed
      metrics: structural (mean volume in specific regions and stretch factor),
      functional (temporal Signal-to-Noise ratio), diffusion (mean Fractional
      Anisotropy and Mean Diffusivity in multiple regions). The proposed frame work of
      imaging metrics should be used to perform daily quality assurance testing and
      incorporated into multi-center studies.

PMID- 23133519
TI  - GPR39 is coupled to TMEM16A in intestinal fibroblast-like cells.
AB  - GPR39 is a GPCR implicated as a regulator of gastrointestinal motility, although
      the mechanism remains elusive. Here, we report that GPR39 is expressed by a
      specific cell population cultured from mouse small intestine muscle layers, which
      was subsequently identified as fibroblast-like cells (FLCs) that have recently
      been shown to modulate gut motility. Application of the GPR39 agonist, Zn(2+),
      induced large currents and membrane depolarization in FLCs cultured from wild
      type mice, but not Gpr39(-/-) mice. This Zn(2+)-induced current could be
      suppressed by application of a TMEM16A antagonist, CaCC(inh)-A01, or by silencing
      Tmem16a expression. These data suggest that GPR39 might modulate gut motility via
      regulating TMEM16A function in FLCs.

PMID- 23133520
TI  - Adaptive color polymorphism and unusually high local genetic diversity in the
      side-blotched lizard, Uta stansburiana.
AB  - Recently, studies of adaptive color variation have become popular as models for
      examining the genetics of natural selection. We examined color pattern
      polymorphism and genetic variation in a population of side-blotched lizards (Uta
      stansburiana) that is found in habitats with both dark (lava) and light colored
      (granite) substrates. We conducted a limited experiment for adult phenotypic
      plasticity in laboratory conditions. We recorded both substrate and lizard color
      patterns in the field to determine whether lizards tended to match their
      substrate. Finally we examined genetic variation in a gene (melanocortin 1
      receptor) that has been shown to affect lizard color in other species and in a
      presumably neutral gene (mitochondrial cytochrome b). Populations were sampled in
      the immediate area of the lava flows as well as from a more distant site to
      examine the role of population structure. Our captive Uta did not change color to
      match their background. We show that side-blotched lizards tend to match the
      substrate on which it was caught in the field and that variation in the
      melanocortin 1 receptor gene does not correlate well with color pattern in this
      population. Perhaps the most remarkable result is that this population of side
      blotched lizards shows extremely high levels of variation at both genetic
      markers, in the sense of allele numbers, with relatively low levels of between
      allele sequence variation. Genetic variation across this small region was as
      great or greater than that seen in samples of pelagic fish species collected
      worldwide. Statistical analysis of genetic variation suggests rapid population
      expansion may be responsible for the high levels of variation.

PMID- 23133521
TI  - Functional characterization of 14 Pht1 family genes in yeast and their
      expressions in response to nutrient starvation in soybean.
AB  - BACKGROUND: Phosphorus (P) is essential for plant growth and development.
      Phosphate (Pi) transporter genes in the Pht1 family play important roles in Pi
      uptake and translocation in plants. Although Pht1 family genes have been well
      studied in model plants, little is known about their functions in soybean, an
      important legume crop worldwide. PRINCIPAL FINDINGS: We identified and isolated a
      complete set of 14 Pi transporter genes (GmPT1-14) in the soybean genome and
      categorized them into two subfamilies based on phylogenetic analysis. Then, an
      experiment to elucidate Pi transport activity of the GmPTs was carried out using
      a yeast mutant defective in high-affinity Pi transport. Results showed that 12 of
      the 14 GmPTs were able to complement Pi uptake of the yeast mutant with Km values
      ranging from 25.7 to 116.3 uM, demonstrating that most of the GmPTs are high
      affinity Pi transporters. Further results from qRT-PCR showed that the
      expressions of the 14 GmPTs differed not only in response to P availability in
      different tissues, but also to other nutrient stresses, including N, K and Fe
      deficiency, suggesting that besides functioning in Pi uptake and translocation,
      GmPTs might be involved in synergistic regulation of mineral nutrient homeostasis
      in soybean. CONCLUSIONS: The comprehensive analysis of Pi transporter function in
      yeast and expression responses to nutrition starvation of Pht1 family genes in
      soybean revealed their involvement in other nutrient homeostasis besides P, which
      could help to better understand the regulation network among ion homeostasis in
      plants.

PMID- 23133522
TI  - Access to artemisinin-combination therapy (ACT) and other anti-malarials:
      national policy and markets in Sierra Leone.
AB  - Malaria remains the leading burden of disease in post-conflict Sierra Leone. To
      overcome the challenge of anti-malarial drug resistance and improve effective
      treatment, Sierra Leone adopted artemisinin-combination therapy artesunate
      amodiaquine (AS+AQ) as first-line treatment for uncomplicated P. falciparum
      malaria. Other national policy anti-malarials include artemether-lumefantrine
      (AL) as an alternative to AS+AQ, quinine and artemether for treatment of
      complicated malaria; and sulphadoxine-pyrimethamine (SP) for intermittent
      preventive treatment (IPTp). This study was conducted to evaluate access to
      national policy recommended anti-malarials. A cross-sectional survey of 127
      medicine outlets (public, private and NGO) was conducted in urban and rural
      areas. The availability on the day of the survey, median prices, and
      affordability policy and available non-policy anti-malarials were calculated.
      Anti-malarials were stocked in 79% of all outlets surveyed. AS+AQ was widely
      available in public medicine outlets; AL was only available in the private and
      NGO sectors. Quinine was available in nearly two-thirds of public and NGO outlets
      and over one-third of private outlets. SP was widely available in all outlets.
      Non-policy anti-malarials were predominantly available in the private outlets.
      AS+AQ in the public sector was widely offered for free. Among the anti-malarials
      sold at a cost, the same median price of a course of AS+AQ (US$1.56), quinine
      tablets (US$0.63), were found in both the public and private sectors. Quinine
      injection had a median cost of US$0.31 in the public sector and US$0.47 in the
      private sector, while SP had a median cost of US$0.31 in the public sector
      compared to US$ 0.63 in the private sector. Non-policy anti-malarials were more
      affordable than first-line AS+AQ in all sectors. A course of AS+AQ was affordable
      at nearly two days' worth of wages in both the public and private sectors.

PMID- 23133523
TI  - Immunogenicity of a fusion protein containing immunodominant epitopes of Ag85C,
      MPT51, and HspX from Mycobacterium tuberculosis in mice and active TB infection.
AB  - Tuberculosis (TB) remains a major global health problem. The only vaccine against
      tuberculosis, attenuated Mycobacterium bovis Bacillus Calmette-Guerin (BCG), has
      demonstrated relatively low efficacy and does not provide satisfactory protection
      against the disease in adults. More effective vaccines and better therapies are
      urgently needed to reduce the global spread of TB. This study evaluated the
      immunogenicity of a recombinant M. tuberculosis Ag85C-MPT51-HspX fusion protein
      (CMX) in mice and individuals with active tuberculosis. BALB/c mice were
      immunized with the CMX protein liposome-encapsulated with CpG DNA or with CpGDNA
      liposome-encapsulated, liposome or saline as negative controls. The immunization
      produced high levels of anti-CMX -specific IgG1 and IgG2a antibodies and induced
      an increase in the relative and absolute numbers of specific TCD4 IFN-gamma(+)
      and TNF-alpha(+) cells in the spleen. Sera from a cohort of individuals with
      active tuberculosis contained higher levels of IgG and IgM that recognized CMX
      when compared to healthy individuals. In conclusion, this protein was shown to be
      immunogenic both in mice and humans.

PMID- 23133524
TI  - Gatifloxacin induces S and G2-phase cell cycle arrest in pancreatic cancer cells
      via p21/p27/p53.
AB  - Pancreatic cancer, despite being the most dreadful among gastrointestinal
      cancers, is poorly diagnosed, and further, the situation has been aggravated
      owing to acquired drug resistance against the single known drug therapy. While
      previous studies have highlighted the growth inhibitory effects of older
      generation fluoroquinolones, the current study aims to evaluate the growth
      inhibitory effects of newer generation fluoroquinolone, Gatifloxacin, on
      pancreatic cancer cell lines MIA PaCa-2 and Panc-1 as well as to elucidate the
      underlying molecular mechanisms. Herein, we report that Gatifloxacin suppresses
      the proliferation of MIA PaCa-2 and Panc-1 cells by causing S and G(2)-phase cell
      cycle arrest without induction of apoptosis. Blockade in S-phase of the cell
      cycle was associated with increased TGF-beta1 expression and translocation of
      Smad3-4 complex to the nucleus with subsequent activation of p21 in MIA PaCa-2
      cells, whereas TGF-beta signalling attenuated Panc-1 cells showed S-phase arrest
      by direct activation of p27. However, Gatifloxacin mediated G(2)-phase cell cycle
      arrest was found to be p53 dependent in both the cell lines. Our study is of
      interest because fluoroquinolones have the ability to penetrate pancreatic tissue
      which can be very effective in combating pancreatic cancers that are usually
      associated with loss or downregulation of CDK inhibitors p21/p27 as well as
      mutational inactivation of p53. Additionally, Gatifloxacin was also found to
      synergize the effect of Gemcitabine, the only known drug against pancreatic
      cancer, as well as the broad spectrum anticancer drug cisplatin. Taken together
      our results suggest that Gatifloxacin possesses anticancer activities against
      pancreatic cancer and is a promising candidate to be repositioned from broad
      spectrum antibiotics to anticancer agent.

PMID- 23133525
TI  - The response of human skin commensal bacteria as a reflection of UV radiation: UV
      B decreases porphyrin production.
AB  - Recent global radiation fears reflect the urgent need for a new modality that can
      simply determine if people are in a radiation risk of developing cancer and other
      illnesses. Ultraviolet (UV) radiation has been thought to be the major risk
      factor for most skin cancers. Although various biomarkers derived from the
      responses of human cells have been revealed, detection of these biomarkers is
      cumbersome, probably requires taking live human tissues, and varies significantly
      depending on human immune status. Here we hypothesize that the reaction of
      Propionibacterium acnes (P. acnes), a human resident skin commensal, to UV
      radiation can serve as early surrogate markers for radiation risk because the
      bacteria are immediately responsive to radiation. In addition, the bacteria can
      be readily accessible and exposed to the same field of radiation as human body.
      To test our hypothesis, P. acnes was exposed to UV-B radiation. The production of
      porphyrins in P. acnes was significantly reduced with increasing doses of UV-B.
      The porphyrin reduction can be detected in both P. acnes and human skin bacterial
      isolates. Exposure of UV-B to P. acnes- inoculated mice led to a significant
      decrease in porphyrin production in a single colony of P. acnes and
      simultaneously induced the formation of cyclobutane pyrimidine dimers (CPD) in
      the epidermal layers of mouse skin. Mass spectrometric analysis via a linear trap
      quadrupole (LTQ)-Orbitrap XL showed that five peptides including an internal
      peptide (THLPTGIVVSCQNER) of a peptide chain release factor 2 (RF2) were oxidized
      by UV-B. Seven peptides including three internal peptides of 60 kDa chaperonin 1
      were de-oxidized by UV-B. When compared to UV-B, gamma radiation also decreased
      the porphyrin production of P. acnes in a dose-dependent manner, but induced a
      different signature of protein oxidation/de-oxidation. We highlight that
      uncovering response of skin microbiome to radiation will facilitate the
      development of pre-symptomatic diagnosis of radiation risk in a battlefield
      exposure, nuclear accidents, terrorist attacks, or cancer imaging/therapy.

PMID- 23133526
TI  - North-American norms for name disagreement: pictorial stimuli naming
      discrepancies.
AB  - Pictorial stimuli are commonly used by scientists to explore central processes;
      including memory, attention, and language. Pictures that have been collected and
      put into sets for these purposes often contain visual ambiguities that lead to
      name disagreement amongst subjects. In the present work, we propose new norms
      which reflect these sources of name disagreement, and we apply this method to two
      sets of pictures: the Snodgrass and Vanderwart (S&V) set and the Bank of
      Standardized Stimuli (BOSS). Naming responses of the presented pictures were
      classified within response categories based on whether they were correct,
      incorrect, or equivocal. To characterize the naming strategy where an alternative
      name was being used, responses were further divided into different sub-categories
      that reflected various sources of name disagreement. Naming strategies were also
      compared across the two sets of stimuli. Results showed that the pictures of the
      S&V set and the BOSS were more likely to elicit alternative specific and
      equivocal names, respectively. It was also found that the use of incorrect names
      was not significantly different across stimulus sets but that errors were more
      likely caused by visual ambiguity in the S&V set and by a misuse of names in the
      BOSS. Norms for name disagreement presented in this paper are useful for
      subsequent research for their categorization and elucidation of name disagreement
      that occurs when choosing visual stimuli from one or both stimulus sets. The
      sources of disagreement should be examined carefully as they help to provide an
      explanation of errors and inconsistencies of many concepts during picture naming
      tasks.

PMID- 23133527
TI  - A formal representation of the WHO and UNICEF estimates of national immunization
      coverage: a computational logic approach.
AB  - Production of official statistics frequently requires expert judgement to
      evaluate and reconcile data of unknown and varying quality from multiple and
      potentially conflicting sources. Moreover, exceptional events may be difficult to
      incorporate in modelled estimates. Computational logic provides a methodology and
      tools for incorporating analyst's judgement, integrating multiple data sources
      and modelling methods, ensuring transparency and replicability, and making
      documentation computationally accessible. Representations using computational
      logic can be implemented in a variety of computer-based languages for automated
      production. Computational logic complements standard mathematical and statistical
      techniques and extends the flexibility of mathematical and statistical modelling.
      A basic overview of computational logic is presented and its application to
      official statistics is illustrated with the WHO & UNICEF estimates of national
      immunization coverage.

PMID- 23133528
TI  - The hepatitis C virus modulates insulin signaling pathway in vitro promoting
      insulin resistance.
AB  - Insulin is critical for controlling energy functions including glucose and lipid
      metabolism. Insulin resistance seems to interact with hepatitis C promoting
      fibrosis progression and impairing sustained virological response to
      peginterferon and ribavirin. The main aim was to elucidate the direct effect of
      hepatitis C virus (HCV) infection on insulin signaling both in vitro analyzing
      gene expression and protein abundance. Huh7.5 cells and JFH-1 viral particles
      were used for in vitro studies. Experiments were conducted by triplicate in
      control cells and infected cells. Genes and proteins involved in insulin
      signaling pathway were modified by HCV infection. Moreover, metformin treatment
      increased gene expression of PI3K, IRS1, MAP3K, AKT and PTEN more than >1.5 fold.
      PTP1B, encoding a tyrosin phosphatase, was found highly induced (>3 fold) in
      infected cells treated with metformin. However, PTP1B protein expression was
      reduced in metformin treated cells after JFH1 infection. Other proteins related
      to insulin pathway like Akt, PTEN and phosphorylated MTOR were also found down
      regulated. Viral replication was inhibited in vitro by metformin. A strong effect
      of HCV infection on insulin pathway-related gene and protein expression was found
      in vitro. These results could lead to the identification of new therapeutic
      targets in HCV infection and its co-morbidities.

PMID- 23133529
TI  - Preferential release of newly synthesized insulin assessed by a multi-label
      reporter system using pancreatic beta-cell line MIN6.
AB  - Newly synthesized hormones have been suggested to be preferentially secreted by
      various neuroendocrine cells. This observation indicates that there is a distinct
      population of secretory granules containing new and old hormones. Recent
      development of fluorescent timer proteins used in bovine adrenal chromaffin cells
      revealed that secretory vesicles segregate into distinct age-dependent
      populations. Here, we verify the preferential release of newly synthesized
      insulin in the pancreatic beta-cell line, MIN6, using a combination of multi
      labeling reporter systems with both fluorescent and biochemical procedures. This
      system allows hormones or granules of any age to be labeled, in contrast to the
      timer proteins, which require fluorescence shift time. Pulse-chase labeling with
      different color probes distinguishes insulin secretory granules by age, with
      younger granules having a predominantly intracellular localization rather than at
      the cell periphery.

PMID- 23133530
TI  - Predictors of business return in New Orleans after Hurricane Katrina.
AB  - We analyzed the business reopening process in New Orleans after Hurricane
      Katrina, which hit the region on August 29, 2005, to better understand what the
      major predictors were and how their impacts changed through time. A telephone
      survey of businesses in New Orleans was conducted in October 2007, 26 months
      after Hurricane Katrina. The data were analyzed using a modified spatial probit
      regression model to evaluate the importance of each predictor variable through
      time. The results suggest that the two most important reopening predictors
      throughout all time periods were the flood depth at the business location and
      business size as represented by its wages in a logarithmic form. Flood depth was
      a significant negative predictor and had the largest marginal effects on the
      reopening probabilities. Smaller businesses had lower reopening probabilities
      than larger ones. However, the nonlinear response of business size to the
      reopening probability suggests that recovery aid would be most effective for
      smaller businesses than for larger ones. The spatial spillovers effect was a
      significant positive predictor but only for the first nine months. The findings
      show clearly that flood protection is the overarching issue for New Orleans. A
      flood protection plan that reduces the vulnerability and length of flooding would
      be the first and foremost step to mitigate the negative effects from climate
      related hazards and enable speedy recovery. The findings cast doubt on the
      current coastal protection efforts and add to the current debate of whether
      coastal Louisiana will be sustainable or too costly to protect from further land
      loss and flooding given the threat of sea-level rise. Finally, a plan to help
      small businesses to return would also be an effective strategy for recovery, and
      the temporal window of opportunity that generates the greatest impacts would be
      the first 6~9 months after the disaster.

PMID- 23133531
TI  - Diversity, molecular characterization and expression of T cell receptor gamma in
      a teleost fish, the sea bass (Dicentrarchus labrax, L).
AB  - Two lineages of T cells, expressing either the alphabeta T cell receptor (TR) or
      the gammadelta TR, exist in Gnathostomes. The latter type of T cells account for
      1-10 % of T cells in blood and up to 30 % in the small intestine. They may
      recognize unconventional antigens (phosphorylated microbial metabolites, lipid
      antigens) without the need of major histocompatibility class I (MH1) or class II
      (MH2) presentation. In this work we have described cloning and structural
      characterization of TR -chain (TRG) from the teleost Dicentrarchus labrax.
      Further, by means of quantitative PCR analysis, we analyzed TRG expression levels
      both in poly I:C stimulated leukocytes in vitro, and following infection with
      betanodavirus in vivo. Two full length cDNAs relative to TRG, with the highest
      peptide and nucleotide identity with Japanese flounder, were identified. A
      multiple alignment analysis showed the conservation of peptides fundamental for
      TRG biological functions, and of the FGXG motif in the FR4 region, typical of
      most TR and immunoglobulin light chains. A 3D structure consisting of two domains
      mainly folded as beta strands with a sandwich architecture for each domain was
      also reported. TRG CDR3 of 8-18 AA in length and diversity in the TRG
      rearrangements expressed in thymus and intestine for a given V/C combination were
      evidenced by junction length spectratyping. TRG mRNA expression levels were high
      in basal conditions both in thymus and intestine, while in kidney and gut
      leukocytes they were up-regulated after in vitro stimulation by poly I:C.
      Finally, in juveniles the TRG expression levels were up-regulated in the head
      kidney and down-regulated in intestine after in vivo infection with
      betanodavirus. Overall, in this study the involvement of TRG-bearing T cells
      during viral stimulation was described for the first time, leading to new
      insights for the identification of T cell subsets in fish.

PMID- 23133532
TI  - Polymorphisms in the inflammatory genes CIITA, CLEC16A and IFNG influence BMD,
      bone loss and fracture in elderly women.
AB  - Osteoclast activity and the fine balance between bone formation and resorption is
      affected by inflammatory factors such as cytokines and T lymphocyte activity,
      mediated by major histocompatibility complex (MHC) molecules, in turn regulated
      by the MHC class II transactivator (MHC2TA). We investigated the effect of
      functional polymorphisms in the MHC2TA gene (CIITA), and two additional genes; C
      type lectin domain 16A (CLEC16A), in linkage disequilibrium with CIITA and
      Interferon-gamma (IFNG), an inducer of CIITA; on bone density, bone resorption
      markers, bone loss and fracture risk in 75 year-old women followed for up to 10
      years (OPRA n = 1003) and in young adult women (PEAK-25 n = 999). CIITA was
      associated with BMD at age 75 (lumbar spine p = 0.011; femoral neck (FN) p =
      0.049) and age 80 (total body p = 0.015; total hip p = 0.042; FN p = 0.028).
      Carriers of the CIITA rs3087456(G) allele had 1.8-3.4% higher BMD and displayed
      increased rate of bone loss between age 75 and 80 (FN p = 0.013; total hip p =
      0.030; total body p = 3.8E(-5)). Despite increasing bone loss, the rs3087456(G)
      allele was protective against incident fracture overall (p = 0.002), osteoporotic
      fracture and hip fracture. Carriers of CLEC16A and IFNG variant alleles had lower
      BMD (p<0.05) and ultrasound parameters and a lower risk of incident fracture
      (CLEC16A, p = 0.011). In 25-year old women, none of the genes were associated
      with BMD. In conclusion, variation in inflammatory genes CIITA, CLEC-16A and INFG
      appear to contribute to bone phenotypes in elderly women and suggest a role for
      low-grade inflammation and MHC class II expression for osteoporosis pathogenesis.

PMID- 23133533
TI  - Comparative genomics of neuroglobin reveals its early origins.
AB  - BACKGROUND: Neuroglobin (Ngb) is a hexacoordinated globin expressed mainly in the
      central and peripheral nervous system of vertebrates. Although several hypotheses
      have been put forward regarding the role of neuroglobin, its definite function
      remains uncertain. Ngb appears to have a neuro-protective role enhancing cell
      viability under hypoxia and other types of oxidative stress. Ngb is
      phylogenetically ancient and has a substitution rate nearly four times lower than
      that of other vertebrate globins, e.g. hemoglobin. Despite its high sequence
      conservation among vertebrates Ngb seems to be elusive in invertebrates.
      PRINCIPAL FINDINGS: We determined candidate orthologs in invertebrates and
      identified a globin of the placozoan Trichoplax adhaerens that is most likely
      orthologous to vertebrate Ngb and confirmed the orthologous relationship of the
      polymeric globin of the sea urchin Strongylocentrotus purpuratus to Ngb. The
      putative orthologous globin genes are located next to genes orthologous to
      vertebrate POMT2 similarly to localization of vertebrate Ngb. The shared syntenic
      position of the globins from Trichoplax, the sea urchin and of vertebrate Ngb
      strongly suggests that they are orthologous. A search for conserved transcription
      factor binding sites (TFBSs) in the promoter regions of the Ngb genes of
      different vertebrates via phylogenetic footprinting revealed several TFBSs, which
      may contribute to the specific expression of Ngb, whereas a comparative analysis
      with myoglobin revealed several common TFBSs, suggestive of regulatory mechanisms
      common to globin genes. SIGNIFICANCE: Identification of the placozoan and
      echinoderm genes orthologous to vertebrate neuroglobin strongly supports the
      hypothesis of the early evolutionary origin of this globin, as it shows that
      neuroglobin was already present in the placozoan-bilaterian last common ancestor.
      Computational determination of the transcription factor binding sites repertoire
      provides on the one hand a set of transcriptional factors that are responsible
      for the specific expression of the Ngb genes and on the other hand a set of
      factors potentially controlling expression of a couple of different globin genes.

PMID- 23133534
TI  - TRPA1 is functionally expressed primarily by IB4-binding, non-peptidergic mouse
      and rat sensory neurons.
AB  - Subpopulations of somatosensory neurons are characterized by functional
      properties and expression of receptor proteins and surface markers. CGRP
      expression and IB4-binding are commonly used to define peptidergic and non
      peptidergic subpopulations. TRPA1 is a polymodal, plasma membrane ion channel
      that contributes to mechanical and cold hypersensitivity during tissue injury,
      making it a key target for pain therapeutics. Some studies have shown that TRPA1
      is predominantly expressed by peptidergic sensory neurons, but others indicate
      that TRPA1 is expressed extensively within non-peptidergic, IB4-binding neurons.
      We used FURA-2 calcium imaging to define the functional distribution of TRPA1
      among peptidergic and non-peptidergic adult mouse (C57BL/6J) DRG neurons.
      Approximately 80% of all small-diameter (<27 um) neurons from lumbar 1-6 DRGs
      that responded to TRPA1 agonists allyl isothiocyanate (AITC; 79%) or
      cinnamaldehyde (84%) were IB4-positive. Retrograde labeling via plantar hind paw
      injection of WGA-Alexafluor594 showed similarly that most (81%) cutaneous neurons
      responding to TRPA1 agonists were IB4-positive. Additionally, we cultured DRG
      neurons from a novel CGRP-GFP mouse where GFP expression is driven by the
      CGRPalpha promoter, enabling identification of CGRP-expressing live neurons.
      Interestingly, 78% of TRPA1-responsive neurons were CGRP-negative. Co-labeling
      with IB4 revealed that the majority (66%) of TRPA1 agonist responders were IB4
      positive but CGRP-negative. Among TRPA1-null DRGs, few small neurons (2-4%)
      responded to either TRPA1 agonist, indicating that both cinnamaldehyde and AITC
      specifically target TRPA1. Additionally, few large neurons (>=27 um diameter)
      responded to AITC (6%) or cinnamaldehyde (4%), confirming that most large
      diameter somata lack functional TRPA1. Comparison of mouse and rat DRGs showed
      that the majority of TRPA1-responsive neurons in both species were IB4-positive.
      Together, these data demonstrate that TRPA1 is functionally expressed primarily
      in the IB4-positive, CGRP-negative subpopulation of small lumbar DRG neurons from
      rodents. Thus, IB4 binding is a better indicator than neuropeptides for TRPA1
      expression.

PMID- 23133535
TI  - Phospho-Akt immunoreactivity in prostate cancer: relationship to disease severity
      and outcome, Ki67 and phosphorylated EGFR expression.
AB  - BACKGROUND: In the present study, we have investigated the prognostic usefulness
      of phosphorylated Akt immunoreactivity (pAkt-IR) in prostate cancer using a well
      characterised tissue microarray from men who had undergone transurethral
      resection due to lower urinary tract symptoms. METHODOLOGY/PRINCIPAL FINDINGS:
      pAkt-IR in prostate epithelial and tumour cells was assessed using a monoclonal
      anti-pAkt (Ser(473)) antibody. Immunoreactive intensity was determined for 282
      (tumour) and 240 (non-malignant tissue) cases. Tumour pAkt-IR scores correlated
      with Gleason score, tumour Ki67-IR (a marker of cell proliferation) and tumour
      phosphorylated epidermal growth factor receptor (pEGFR)-IR. For cases followed
      with expectancy, a high tumour pAkt-IR was associated with a poor disease
      specific survival, and the prognostic information provided by this biomarker was
      additive to that provided by either (but not both) tumour pEFGR-IR or Ki67-IR.
      Upon division of the cases with respect to their Gleason scores, the prognostic
      value of pAkt-IR was seen for patients with Gleason score 8-10, but not for
      patients with Gleason score 6-7. CONCLUSIONS/SIGNIFICANCE: Tumour pAkt-IR is
      associated with both disease severity and disease-specific survival. However, its
      clinical use as a biomarker is limited, since it does not provide prognostic
      information in patients with Gleason scores 6-7.

PMID- 23133536
TI  - Detection of long non-coding RNA in archival tissue: correlation with polycomb
      protein expression in primary and metastatic breast carcinoma.
AB  - A major function of long non-coding RNAs (lncRNAs) is regulating gene expression
      through changes in chromatin state. Experimental evidence suggests that in
      cancer, they can influence Polycomb Repressive Complexes (PRC) to retarget to an
      occupancy pattern resembling that of the embryonic state. We have previously
      demonstrated that the expression level of lncRNA in the HOX locus, including
      HOTAIR, is a predictor of breast cancer metastasis. In this current project, RNA
      in situ hybridization of probes to three different lncRNAs (HOTAIR, ncHoxA1, and
      ncHoxD4), as well a immunohistochemical staining of EZH2, is undertaken in
      formalin-fixed paraffin-embedded breast cancer tissues in a high throughput
      tissue microarray format to correlate expression with clinicopathologic features.
      Though overall EZH2 and HOTAIR expression levels were highly correlated, the
      subset of cases with strong HOTAIR expression correlated with ER and PR
      positivity, while the subset of cases with strong EZH2 expression correlated with
      an increased proliferation rate, ER and PR negativity, HER2 underexpression, and
      triple negativity. Co-expression of HOTAIR and EZH2 trended with a worse outcome.
      In matched primary and metastatic cancers, both HOTAIR and EZH2 had increased
      expression in the metastatic carcinomas. This is the first study to show that RNA
      in situ hybridization of formalin fixed paraffin-embedded clinical material can
      be used to measure levels of long non-coding RNAs. This approach offers a method
      to make observations on lncRNAs that may influence the cancer epigenome in a
      tissue-based technique.

PMID- 23133537
TI  - Mortality and suicide risk in treatment-resistant depression: an observational
      study of the long-term impact of intervention.
AB  - Major depressive disorder is a common global disease that causes a significant
      societal burden. Most interventional studies of depression provide a limited
      assessment of the interventions on mortality and suicide risks. This study
      utilizes data from an observational registry of patients with major depressive
      disorder to determine the impact of intervention (vagus nerve stimulation or
      standard pharmacological/non-pharmacological therapy) and a latent factor,
      patient trajectory toward response, on mortality, suicide and suicidal ideation.
      A total of 636 patients were available for an intent-to-treat analysis of all
      cause mortality, suicide and suicidal ideation. Patients treated with vagus nerve
      stimulation in addition to standard therapies experienced lower, but not
      statistically significant, all-cause mortality (vagus nerve stimulation 4.93 per
      1,000 person-years vs. 10.02 per 1,000 patient years for treatment as usual) and
      suicide rates (vagus nerve stimulation 0.88 per 1,000 person-years vs. 1.61 per
      1,000 patient years for treatment as usual). Treatment with vagus nerve
      stimulation produced a statistically lower relative risk of suicidal ideation
      0.80, 95% confidence interval (0.68,0.95). Further, patients that responded to
      either treatment saw a 51% reduction in relative risk of suicidal behavior;
      relative risk and 95% confidence interval of 0.49 (0.41,0.58). In summary, we
      find that treatment with adjunctive vagus nerve stimulation can potentially lower
      the risk of all-cause mortality, suicide and suicide attempts.

PMID- 23133538
TI  - Modeling of tumor progression in NSCLC and intrinsic resistance to TKI in loss of
      PTEN expression.
AB  - EGFR signaling plays a very important role in NSCLC. It activates Ras/ERK,
      PI3K/Akt and STAT activation pathways. These are the main pathways for cell
      proliferation and survival. We have developed two mathematical models to relate
      to the different EGFR signaling in NSCLC and normal cells in the presence or
      absence of EGFR and PTEN mutations. The dynamics of downstream signaling pathways
      vary in the disease state and activation of some factors can be indicative of
      drug resistance. Our simulation denotes the effect of EGFR mutations and
      increased expression of certain factors in NSCLC EGFR signaling on each of the
      three pathways where levels of pERK, pSTAT and pAkt are increased. Over
      activation of ERK, Akt and STAT3 which are the main cell proliferation and
      survival factors act as promoting factors for tumor progression in NSCLC. In case
      of loss of PTEN, Akt activity level is considerably increased. Our simulation
      results show that in the presence of erlotinib, downstream factors i.e. pAkt,
      pSTAT3 and pERK are inhibited. However, in case of loss of PTEN expression in the
      presence of erlotinib, pAkt level would not decrease which demonstrates that
      these cells are resistant to erlotinib.

PMID- 23133539
TI  - Tissue-specific distribution of secondary metabolites in rapeseed (Brassica napus
      L.).
AB  - Four different parts, hypocotyl and radicle (HR), inner cotyledon (IC), outer
      cotyledon (OC), seed coat and endosperm (SE), were sampled from mature rapeseed
      (Brassica napus L.) by laser microdissection. Subsequently, major secondary
      metabolites, glucosinolates and sinapine, as well as three minor ones, a cyclic
      spermidine conjugate and two flavonoids, representing different compound
      categories, were qualified and quantified in dissected samples by high
      performance liquid chromatography with diode array detection and mass
      spectrometry. No qualitative and quantitative difference of glucosinolates and
      sinapine was detected in embryo tissues (HR, IC and OC). On the other hand, the
      three minor compounds were observed to be distributed unevenly in different
      rapeseed tissues. The hypothetic biological functions of the distribution
      patterns of different secondary metabolites in rapeseed are discussed.

PMID- 23133540
TI  - Phylogenetic analysis of microbial communities in different regions of the
      gastrointestinal tract in Panaque nigrolineatus, a wood-eating fish.
AB  - The Neotropical detritivorous catfish Panaque nigrolineatus imbibes large
      quantities of wood as part of its diet. Due to the interest in cellulose, hemi
      cellulose and lignin degradation pathways, this organism provides an interesting
      model system for the detection of novel microbial catabolism. In this study, we
      characterize the microbial community present in different regions of the
      alimentary tract of P. nigrolineatus fed a mixed diet of date palm and palm wood
      in laboratory aquaria. Analysis was performed on 16S rRNA gene clone libraries
      derived from anterior and posterior regions of the alimentary tract and the
      auxiliary lobe (AL), an uncharacterized organ that is vascularly attached to the
      midgut. Sequence analysis and phylogenetic reconstruction revealed distinct
      microbial communities in each tissue region. The foregut community shared many
      phylotypes in common with aquarium tank water and included Legionella and
      Hyphomicrobium spp. As the analysis moved further into the gastrointestinal
      tract, phylotypes with high levels of 16S rRNA sequence similarity to nitrogen
      fixing Rhizobium and Agrobacterium spp. and Clostridium xylanovorans and
      Clostridium saccharolyticum, dominated midgut and AL communities. However, the
      hindgut was dominated almost exclusively by phylotypes with the highest 16S rRNA
      sequence similarity to the Cytophaga-Flavobacterium-Bacteroides phylum. Species
      richness was highest in the foregut (Chao(1) = 26.72), decreased distally through
      the midgut (Chao(1) = 25.38) and hindgut (Chao(1) = 20.60), with the lowest
      diversity detected in the AL (Chao(1) = 18.04), indicating the presence of a
      specialized microbial community. Using 16S rRNA gene phylogeny, we report that
      the P. nigrolineatus gastrointestinal tract possesses a microbial community
      closely related to microorganisms capable of cellulose degradation and nitrogen
      fixation. Further studies are underway to determine the role of this resident
      microbial community in Panaque nigrolineatus.

PMID- 23133541
TI  - Investigation of CD28 gene polymorphisms in patients with sporadic breast cancer
      in a Chinese Han population in Northeast China.
AB  - BACKGROUND: CD28 is one of a number of costimulatory molecules that play crucial
      roles in immune regulation and homeostasis. Accumulating evidence indicates that
      immune factors influence breast carcinogenesis. To clarify the relationships
      between polymorphisms in the CD28 gene and breast carcinogenesis, a case-control
      study was conducted in women from Heilongjiang Province in northeast of China.
      METHODOLOGY/PRINCIPAL FINDINGS: Our research subjects consisted of 565 female
      patients with sporadic breast cancer and 605 age- and sex-matched healthy
      controls. In total, 12 single nucleotide polymorphisms (SNPs) in the CD28 gene
      were successfully determined using the polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) method. The relationship between the CD28
      variants and clinical features, including histological grade, tumor size, lymph
      node metastasis, human epidermal growth factor receptor 2 (C-erbB2), estrogen
      receptor (ER), progesterone receptor (PR), and tumor protein 53 (P53) status were
      analyzed. A statistically significant association was observed between rs3116496
      and breast cancer risk under different genetic models (additive P = 0.0164,
      dominant P = 0.0042). Different distributions of the rs3116496 'T' allele were
      found in patients and controls, which remained significant after correcting the P
      value for multiple testing using Haploview with 10,000 permutations (corrected P
      = 0.0384). In addition, significant associations were observed between
      rs3116487/rs3116494 (D' = 1, r(2) = 0.99) and clinicopathological features such
      as C-erbB2 and ER status, in breast cancer patients. CONCLUSIONS/SIGNIFICANCE:
      Our findings indicate that CD28 gene polymorphisms contribute to sporadic breast
      cancer risk and have a significant association with clinicopathological features
      in a northeast Chinese Han population.

PMID- 23133542
TI  - A focused ethnographic study of Sri Lankan government field veterinarians'
      decision making about diagnostic laboratory submissions and perceptions of
      surveillance.
AB  - The global public health community is facing the challenge of emerging infectious
      diseases. Historically, the majority of these diseases have arisen from animal
      populations at lower latitudes where many nations experience marked resource
      constraints. In order to minimize the impact of future events, surveillance of
      animal populations will need to enable prompt event detection and response. Many
      surveillance systems targeting animals rely on veterinarians to submit cases to a
      diagnostic laboratory or input clinical case data. Therefore understanding
      veterinarians' decision-making process that guides laboratory case submission and
      their perceptions of infectious disease surveillance is foundational to
      interpreting disease patterns reported by laboratories and engaging veterinarians
      in surveillance initiatives. A focused ethnographic study was conducted with
      twelve field veterinary surgeons that participated in a mobile phone-based
      surveillance pilot project in Sri Lanka. Each participant agreed to an individual
      in-depth interview that was recorded and later transcribed to enable thematic
      analysis of the interview content. Results found that field veterinarians in Sri
      Lanka infrequently submit cases to laboratories--so infrequently that common case
      selection principles could not be described. Field veterinarians in Sri Lanka
      have a diagnostic process that operates independently of laboratories.
      Participants indicated a willingness to take part in surveillance initiatives,
      though they highlighted a need for incentives that satisfy a range of motivations
      that vary among field veterinarians. This study has implications for the future
      of animal health surveillance, including interpretation of disease patterns
      reported, system design and implementation, and engagement of data providers.

PMID- 23133543
TI  - Serum and cerebrospinal fluid levels of transthyretin in Lewy body disorders with
      and without dementia.
AB  - Parkinson's disease (PD) without (non-demented, PDND) and with dementia (PDD),
      and dementia with Lewy bodies (DLB) are subsumed under the umbrella term Lewy
      body disorders (LBD). The main component of the underlying pathologic substrate,
      i.e. Lewy bodies and Lewy neurites, is misfolded alpha-synuclein (Asyn), and--in
      particular in demented LBD patients--co-occurring misfolded amyloid-beta (Abeta).
      Lowered blood and cerebrospinal fluid (CSF) levels of transthyretin (TTR)--a
      clearance protein mainly produced in the liver and, autonomously, in the choroid
      plexus--are associated with Abeta accumulation in Alzheimer's disease. In
      addition, a recent study suggests that TTR is involved in Asyn clearance. We
      measured TTR protein levels in serum and cerebrospinal fluid of 131 LBD patients
      (77 PDND, 26 PDD, and 28 DLB) and 72 controls, and compared TTR levels with
      demographic and clinical data as well as neurodegenerative markers in the CSF.
      Five single nucleotide polymorphisms of the TTR gene which are considered to
      influence the ability of the protein to carry its ligands were also analyzed. CSF
      TTR levels were significantly higher in LBD patients compared to controls. Post
      hoc analysis demonstrated that this effect was driven by PDND patients. In
      addition, CSF TTR levels correlated negatively with CSF Abeta(1-42), total tau
      and phospho-tau levels. Serum TTR levels did not significantly differ among the
      studied groups. There were no relevant associations between TTR levels and
      genetic, demographic and clinical data, respectively. These results suggest an
      involvement of the clearance protein TTR in LBD pathophysiology, and should
      motivate to elucidate TTR-related mechanisms in LBD in more detail.

PMID- 23133544
TI  - Increased residual force enhancement in older adults is associated with a
      maintenance of eccentric strength.
AB  - Despite an age-related loss of voluntary isometric and concentric strength,
      muscle strength is well maintained during lengthening muscle actions (i.e.,
      eccentric strength) in old age. Additionally, in younger adults during
      lengthening of an activated skeletal muscle, the force level observed following
      the stretch is greater than the isometric force at the same muscle length. This
      feature is termed residual force enhancement (RFE) and is believed to be a
      combination of active and passive components of the contractile apparatus. The
      purpose of this study was to provide an initial assessment of RFE in older adults
      and utilize aging as a muscle model to explore RFE in a system in which isometric
      force production is compromised, but structural mechanisms of eccentric strength
      are well-maintained. Therefore, we hypothesised that older adults will experience
      greater RFE compared with young adults. Following a reference maximal voluntary
      isometric contraction (MVC) of the dorsiflexors in 10 young (26.1 +/- 2.7 y) and
      10 old (76.0 +/- 6.5 y) men, an active stretch was performed at 15 degrees /s
      over a 30 degrees  ankle joint excursion ending at the same muscle length as the
      reference MVCs (40 degrees  of plantar flexion). Any additional torque compared
      with the reference MVC therefore represented RFE. In older men RFE was ~2.5 times
      greater compared to young. The passive component of force enhancement contributed
      ~37% and ~20% to total force enhancement, in old and young respectively. The
      positive association (R(2) = 0.57) between maintained eccentric strength in old
      age and RFE indicates age-related mechanisms responsible for the maintenance of
      eccentric strength likely contributed to the observed elevated RFE. Additionally,
      as indicated by the greater passive force enhancement, these mechanisms may be
      related to increased muscle series elastic stiffness in old age.

PMID- 23133545
TI  - Mechanical disruption of tumors by iron particles and magnetic field application
      results in increased anti-tumor immune responses.
AB  - The primary tumor represents a potential source of antigens for priming immune
      responses for disseminated disease. Current means of debulking tumors involves
      the use of cytoreductive conditioning that impairs immune cells or removal by
      surgery. We hypothesized that activation of the immune system could occur through
      the localized release of tumor antigens and induction of tumor death due to
      physical disruption of tumor architecture and destruction of the primary tumor in
      situ. This was accomplished by intratumor injection of magneto-rheological fluid
      (MRF) consisting of iron microparticles, in Balb/c mice bearing orthotopic 4T1
      breast cancer, followed by local application of a magnetic field resulting in
      immediate coalescence of the particles, tumor cell death, slower growth of
      primary tumors as well as decreased tumor progression in distant sites and
      metastatic spread. This treatment was associated with increased activation of DCs
      in the draining lymph nodes and recruitment of both DCs and CD8(+)T cells to the
      tumor. The particles remained within the tumor and no toxicities were observed.
      The immune induction observed was significantly greater compared to cryoablation.
      Further anti-tumor effects were observed when MRF/magnet therapy was combined
      with systemic low dose immunotherapy. Thus, mechanical disruption of the primary
      tumor with MRF/magnetic field application represents a novel means to induce
      systemic immune activation in cancer.

PMID- 23133546
TI  - Informal allopathic provider knowledge and practice regarding hypertension in
      urban and rural Bangladesh.
AB  - OBJECTIVES: Describe informal allopathic practitioner (IAP) knowledge and
      practice about management of hypertension and identify gaps in IAP knowledge and
      practice amenable to interventions. METHODS: A cross sectional descriptive survey
      of 642 IAPs in Kamalapur (urban) and Mirsarai (rural) Bangladesh was conducted
      from March to April, 2011. Using a structured, pre-tested questionnaire
      sociodemographic, training, knowledge and practice data about management of
      hypertension was collected. Comparative statistics were preformed to show
      differences between urban and rural practitioners using SAS 8.0. FINDINGS: 99.4%
      of IAPs were male, mean age was 37.5 (12.5 SD) years. Greater than 65% correctly
      identified the upper limit of normal blood pressure. 50.2% underestimated lower
      limit of systolic hypertension. 79.8% allowed age to affect their treatment
      approach. As blood pressure increased, willingness to treat with medication
      decreased and tendency to refer increased. Sedative/sleeping pills,
      antidepressants, and beta blockers were the most commonly prescribed medications
      for prehypertension (58.7%, 50.3% and 53.7% respectively), stage I hypertension
      (55.0%, 38.6%, 49.8% respectively) and stage II hypertension (42.4%, 23.7%, and
      28.8% respectively). Rural IAPs were more likely than urban IAPs to treat (84.7%
      vs 77.7%), order tests (27.1% vs 6.0%) and write prescriptions (60.4% vs 18.7%).
      CONCLUSION: While IAPs are crucial to Bangladesh's pluralistic healthcare system,
      gaps in knowledge and practice could cause unnecessary harm. To include IAPs in
      the public sector's fight against the chronic disease epidemic, interventions
      aimed at standardizing IAPs knowledge and practice will be essential.
      Successfully utilizing IAPs will have beneficial implications not only for
      Bangladesh, but for all developing countries.

PMID- 23133547
TI  - Rubber elongation factor (REF), a major allergen component in Hevea brasiliensis
      latex has amyloid properties.
AB  - REF (Hevb1) and SRPP (Hevb3) are two major components of Hevea brasiliensis
      latex, well known for their allergenic properties. They are obviously taking part
      in the biosynthesis of natural rubber, but their exact function is still unclear.
      They could be involved in defense/stress mechanisms after tapping or directly
      acting on the isoprenoid biosynthetic pathway. The structure of these two
      proteins is still not described. In this work, it was discovered that REF has
      amyloid properties, contrary to SRPP. We investigated their structure by CD, TEM,
      ATR-FTIR and WAXS and neatly showed the presence of beta-sheet organized
      aggregates for REF, whereas SRPP mainly fold as a helical protein. Both proteins
      are highly hydrophobic but differ in their interaction with lipid monolayers used
      to mimic the monomembrane surrounding the rubber particles. Ellipsometry
      experiments showed that REF seems to penetrate deeply into the monolayer and SRPP
      only binds to the lipid surface. These results could therefore clarify the role
      of these two paralogous proteins in latex production, either in the coagulation
      of natural rubber or in stress-related responses. To our knowledge, this is the
      first report of an amyloid formed from a plant protein. This suggests also the
      presence of functional amyloid in the plant kingdom.

PMID- 23133548
TI  - Circulating angiogenic cells can be derived from cryopreserved peripheral blood
      mononuclear cells.
AB  - BACKGROUND: Cell transplantation for regenerative medicine has become an
      appealing therapeutic method; however, stem and progenitor cells are not always
      freshly available. Cryopreservation offers a way to freeze cells as they are
      generated, for storage and transport until required for therapy. This study was
      performed to assess the feasibility of cryopreserving peripheral blood
      mononuclear cells (PBMCs) for the subsequent in vitro generation of their derived
      therapeutic population, circulating angiogenic cells (CACs). METHODS: PBMCs were
      isolated from healthy human donors. Freshly isolated cells were either analyzed
      immediately or cryopreserved in media containing 6% plasma serum and 5% dimethyl
      sulfoxide. PBMCs were thawed after being frozen for 1 (early thaw) or 28 (late
      thaw) days and analyzed, or cultured for 4 days to generate CACs. Analysis of the
      cells consisted of flow cytometry for viability and phenotype, as well as
      functional assays for their adhesion and migration potential, cytokine secretion,
      and in vivo angiogenic potential. RESULTS: The viability of PBMCs and CACs as
      well as their adhesion and migration properties did not differ greatly after
      cryopreservation. Phenotypic changes did occur in PBMCs and to a lesser extent in
      CACs after freezing; however the potent CD34(+)VEGFR2(+)CD133(+) population
      remained unaffected. The derived CACs, while exhibiting changes in inflammatory
      cytokine secretion, showed no changes in the secretion of important regenerative
      and chemotactic cytokines, nor in their ability to restore perfusion in ischemic
      muscle. CONCLUSION: Overall, it appears that changes do occur in cryopreserved
      PBMCs and their generated CACs; however, the CD34(+)VEGFR2(+)CD133(+) progenitor
      population, the secretion of pro-vasculogenic factors, and the in vivo angiogenic
      potential of CACs remain unaffected by cryopreservation.

PMID- 23133549
TI  - Effects and safety of calcimimetics in end stage renal disease patients with
      secondary hyperparathyroidism: a meta-analysis.
AB  - PURPOSE: Secondary hyperparathyroidism (SHPT) is one of the most common
      abnormalities of mineral metabolism in patients with chronic kidney disease. We
      performed a meta-analysis to determine the effect and safety of cinacalcet in
      SHPT patients receiving dialysis. METHODS: The meta-analysis was performed to
      determine the effect and safety of cinacalcet in SHPT patients receiving dialysis
      by using the search terms 'cinacalcet' or 'mimpara' or 'sensipar' or
      'calcimimetic' or 'R586' on MEDLINE and EMBASE (January 1990 to February 2012).
      RESULTS: Fifteen trials were included, all of which were performed between 2000
      and 2011 enrolling a total of 3387 dialysis patients. Our study showed that
      calcimimetic agents effectively ameliorated iPTH levels(WMD, -294.36 pg/mL; 95%
      CI, -322.76 to -265.95, P<0.001) in SHPT patients and reduced serum calcium (WMD,
      -0.81 mg/dL; 95% CI, -0.89 to -0.72, P<0.001) and phosphorus disturbances(WMD, 
      0.29 mg/dL; 95% CI, -0.41 to -0.17, P<0.001). The percentage of patients in whom
      there was a 30% decrease in serum iPTH levels by the end of the dosing was higher
      in cinacalcet group than that in control group(OR = 10.75, 95% CI: 6.65-17.37,
      P<0.001). However, no significant difference was found in all-cause mortality and
      all adverse events between calcimimetics and control groups(OR = 0.86, 95% CI:
      0.46-1.60, P = 0.630; OR = 1.30, 95% CI: 0.78-2.18, P = 0.320, respectively).
      Compared with the control therapy, there was a significant increase in the
      episodes of hypocalcemia (OR = 2.46, 95% CI: 1.58-3.82, P<0.001), nausea (OR =
      2.45, 95% CI: 1.29-4.66, P = 0.006), vomiting(OR = 2.78, 95% CI: 2.14-3.62,
      P<0.001), diarrhea(OR = 1.51, 95% CI: 1.04-2.20, P = 0.030) and upper respiratory
      tract infection (OR = 1.79, 95% CI: 1.20-2.66, P = 0.004)in calcimimetics group.
      CONCLUSIONS: Calcimimetic treatment effectively improved biochemical parameters
      of SHPT patients receiving dialysis without increasing all-cause mortality and
      all adverse events.

PMID- 23133550
TI  - Geographical variations in sex ratio trends over time in multiple sclerosis.
AB  - BACKGROUND: A female/male (F/M) ratio increase over time in multiple sclerosis
      (MS) patients was demonstrated in many countries around the world. So far, a
      direct comparison of sex ratio time-trends among MS populations from different
      geographical areas was not carried out. OBJECTIVE: In this paper we assessed and
      compared sex ratio trends, over a 60-year span, in MS populations belonging to
      different latitudinal areas. METHODS: Data of a cohort of 15,996 (F = 11,290; M =
      4,706) definite MS with birth years ranging from 1930 to 1989 were extracted from
      the international MSBase registry and the New Zealand MS database. Gender ratios
      were calculated by six decades based on year of birth and were adjusted for the
      F/M born-alive ratio derived from the respective national registries of births.
      RESULTS: Adjusted sex ratios showed a significant increase from the first to the
      last decade in the whole MS sample (from 2.35 to 2.73; p = 0.03) and in the
      subgroups belonging to the areas between 83 degrees  N and 45 degrees  N (from
      1.93 to 4.55; p<0.0001) and between 45 degrees  N to 35 degrees  N (from 1.46 to
      2.30; p<0.05) latitude, while a sex ratio stability over time was found in the
      subgroup from areas between 12 degrees  S and 55 degrees  S latitude. The sex
      ratio increase mainly affected relapsing-remitting (RR) MS. CONCLUSIONS: Our
      results confirm a general sex ratio increase over time in RRMS and also
      demonstrate a latitudinal gradient of this increase. These findings add useful
      information for planning case-control studies aimed to explore sex-related
      factors responsible for MS development.

PMID- 23133551
TI  - Leukocyte ABCA1 remains atheroprotective in splenectomized LDL receptor knockout
      mice.
AB  - AIM: ATP-binding cassette transporter A1 (ABCA1) is an important mediator of
      macrophage cholesterol efflux. It mediates the efflux of cellular cholesterol to
      lipid-poor apolipoprotein A-I. LDL receptor (LDLr) knockout (KO) mice deficient
      for leukocyte ABCA1 (ABCA1 KO->LDLr KO) show increased atherosclerosis and
      splenic lipid accumulation despite largely attenuated serum cholesterol levels.
      In the present study, we aimed to explore the importance of the spleen for the
      atheroprotective effects of leukocyte ABCA1. METHODS: LDLr KO mice were
      transplanted with bone marrow from ABCA1 KO mice or wild-type (WT) controls.
      After 8 weeks recovery, mice were either splenectomized (SP-x) or underwent a
      sham operation, and were subsequently challenged with a Western-type diet (WTD).
      RESULTS: In agreement with previous studies, the atherosclerotic lesion area in
      ABCA1 KO->LDLr KO sham animals (655 +/- 82 * 10(3) um(2)) was 1.4-fold (p = 0.03)
      larger compared to sham WT->LDLr KO mice (459 +/- 33 * 10(3) um(2)) after 8 weeks
      WTD feeding, despite 1.7-fold (p<0.001) lower serum cholesterol levels.
      Interestingly, deletion of ABCA1 in leukocytes led to 1.6-fold higher neutrophil
      content in the spleen in absence of differences in circulating neutrophils.
      Levels of KC, an important chemoattractant for neutrophils, in serum, however,
      were increased 2.9-fold (p = 0.07) in ABCA1 KO->LDLr KO mice. SP-x induced blood
      neutrophilia as compared to WT->LDLr KO mice (1.9-fold; p<0.05), but did not
      evoke differences in serum cholesterol and anti-oxLDL antibody levels.
      Atherosclerotic lesion development, however, was 1.3-fold induced both in the
      presence and absence of leukocyte ABCA1 (WT: 614 +/- 106 * 10(3) um(2), ABCA1 KO:
      786 +/- 44 * 10(3) um(2)). Two-way ANOVA revealed independent effects on
      atherosclerosis for both leukocyte ABCA1 deficiency and SP-x (p<0.05).
      CONCLUSIONS: The observed splenic alterations induced by leukocyte ABCA1
      deficiency do not play a significant role in the anti-atherogenic effects of
      leukocyte ABCA1 on lesion development.

PMID- 23133552
TI  - Modulation of the osteosarcoma expression phenotype by microRNAs.
AB  - BACKGROUND: Osteosarcomas are the most common primary malignant tumors of bone
      and show multiple and complex genomic aberrations. miRNAs are non-coding RNAs
      capable of regulating gene expression at the post transcriptional level, and
      miRNAs and their target genes may represent novel therapeutic targets or
      biomarkers for osteosarcoma. In order to investigate the involvement of miRNAs in
      osteosarcoma development, global microarray analyses of a panel of 19 human
      osteosarcoma cell lines was performed. PRINCIPAL FINDINGS: We identified 177
      miRNAs that were differentially expressed in osteosarcoma cell lines relative to
      normal bone. Among these, miR-126/miR-126*, miR-142-3p, miR-150, miR-223, miR-486
      5p and members of the miR-1/miR-133a, miR-144/miR-451, miR-195/miR-497 and miR
      206/miR-133b clusters were found to be downregulated in osteosarcoma cell lines.
      All miRNAs in the paralogous clusters miR-17-92, miR-106b-25 and miR-106a-92 were
      overexpressed. Furthermore, the upregulated miRNAs included miR-9/miR-9*, miR
      21*, miR-31/miR-31*, miR-196a/miR-196b, miR-374a and members of the miR-29 and
      miR-130/301 families. The most interesting inversely correlated miRNA/mRNA pairs
      in osteosarcoma cell lines included miR-9/TGFBR2 and miR-29/p85alpha regulatory
      subunit of PI3K. PTEN mRNA correlated inversely with miR-92a and members of the
      miR-17 and miR-130/301 families. Expression profiles of selected miRNAs were
      confirmed in clinical samples. A set of miRNAs, miR-1, miR-18a, miR-18b, miR-19b,
      miR-31, miR-126, miR-142-3p, miR-133b, miR-144, miR-195, miR-223, miR-451 and miR
      497 was identified with an intermediate expression level in osteosarcoma clinical
      samples compared to osteoblasts and bone, which may reflect the differentiation
      level of osteosarcoma relative to the undifferentiated osteoblast and fully
      differentiated normal bone. SIGNIFICANCE: This study provides an integrated
      analysis of miRNA and mRNA in osteosarcoma, and gives new insight into the
      complex genetic mechanisms of osteosarcoma development and progression.

PMID- 23133554
TI  - Positive association between hepatitis C infection and oral cavity cancer: a
      nationwide population-based cohort study in Taiwan.
AB  - OBJECTIVES: The association between viral hepatitis (B and C) and oral cavity
      cancer has been widely debated. This nationwide, population-based cohort study
      assessed the subsequent risk of oral cavity cancer among patients with chronic
      viral hepatitis infection. MATERIALS AND METHODS: Data were retrieved from
      insurance claims data of 1,000,000 randomly sampled individuals covered under the
      Taiwan National Health Insurance system. We identified a total of 21,199 adults
      with chronic viral hepatitis infection (12,369 with HBV alone, 5,311 with HCV
      alone, and 3,519 with HBV/HCV dual infections) from 2000-2005. Comparison group
      comprised 84,796 sex- and age-matched subjects without viral hepatitis during the
      same study period. Incidence and risk of subsequent oral cavity cancer were
      measured until 2008. RESULTS: The incidence of oral cavity cancers was 2.28-fold
      higher among patients with HCV alone than non-viral hepatitis group (6.15 versus
      2.69 per 10,000 person-years). After adjusting for sociodemographic covariates,
      HCV alone was significantly associated with an increased risk for oral cavity
      cancer (hazard ratio (HR) = 1.90, 95% confidence interval (CI) = 1.20-3.02). This
      positive association was highest among individuals in the 40-49-year age group
      (HR = 2.57, 95% CI = 1.21-5.46). However, there were no significant associations
      between HBV alone or HBV/HCV dual infections and risk for oral cavity cancer.
      CONCLUSION: Our data suggest that HCV but not HBV infection is a risk factor for
      oral cavity cancer. In addition, subjects with HCV infection tend to be at early
      onset risk for oral cavity cancer. This finding needs to be replicated in further
      studies.

PMID- 23133555
TI  - In vivo blood glucose quantification using Raman spectroscopy.
AB  - We here propose a novel Raman spectroscopy method that permits the noninvasive
      measurement of blood glucose concentration. To reduce the effects of the strong
      background signals produced by surrounding tissue and to obtain the fingerprint
      Raman lines formed by blood analytes, a laser was focused on the blood in vessels
      in the skin. The Raman spectra were collected transcutaneously. Characteristic
      peaks of glucose (1125 cm(-1)) and hemoglobin (1549 cm(-1)) were observed.
      Hemoglobin concentration served as an internal standard, and the ratio of the
      peaks that appeared at 1125 cm(-1) and 1549 cm(-1) peaks was used to calculate
      the concentration of blood glucose. We studied three mouse subjects whose blood
      glucose levels became elevated over a period of 2 hours using a glucose test
      assay. During the test, 25 Raman spectra were collected transcutaneously and
      glucose reference values were provided by a blood glucose meter. Results clearly
      showed the relationship between Raman intensity and concentration. The release
      curves were approximately linear with a correlation coefficient of 0.91. This
      noninvasive methodology may be useful for the study of blood glucose in vivo.

PMID- 23133556
TI  - The homeobox BcHOX8 gene in Botrytis cinerea regulates vegetative growth and
      morphology.
AB  - Filamentous growth and the capacity at producing conidia are two critical aspects
      of most fungal life cycles, including that of many plant or animal pathogens.
      Here, we report on the identification of a homeobox transcription factor encoding
      gene that plays a role in these two particular aspects of the development of the
      phytopathogenic fungus Botrytis cinerea. Deletion of the BcHOX8 gene in both the
      B. cinerea B05-10 and T4 strains causes similar phenotypes, among which a curved,
      arabesque-like, hyphal growth on hydrophobic surfaces; the mutants were hence
      named Arabesque. Expression of the BcHOX8 gene is higher in conidia and infection
      cushions than in developing appressorium or mycelium. In the Arabesque mutants,
      colony growth rate is reduced and abnormal infection cushions are produced.
      Asexual reproduction is also affected with abnormal conidiophore being formed,
      strongly reduced conidia production and dramatic changes in conidial morphology.
      Finally, the mutation affects the fungus ability to efficiently colonize
      different host plants. Analysis of the B. cinerea genome shows that BcHOX8 is one
      member of a nine putative homeobox genes family. Available gene expression data
      suggest that these genes are functional and sequence comparisons indicate that
      two of them would be specific to B. cinerea and its close relative Sclerotinia
      sclerotiorum.

PMID- 23133557
TI  - Seroepidemiology of Toxoplasma gondii Infection among healthy blood donors in
      Taiwan.
AB  - Toxoplasma gondii is an opportunistic, zoonotic pathogen with a worldwide
      distribution. There are large variations in the seroprevalence of T. gondii
      infection in different regions of the world. Although toxoplasmosis became a
      notifiable communicable disease in Taiwan in 2007, little is known about its
      epidemiology among the general population. This cross-sectional study aimed to
      survey the seroprevalence of T. gondii infection and its risk factors among
      healthy blood donors in Taiwan. Through collaborating with the Taiwan Blood
      Services Foundation, a total of 1,783 healthy blood donors from all six-branch
      blood service centers participated in this study. The blood samples were tested
      for the presence of T. gondii antibodies and DNA using enzyme immunoassays and
      real-time PCR, respectively. Structured questionnaires were used to gather
      information on risk factors for T. gondii infection. Of the 1,783 participants,
      166 (9.3%) tested positive for anti-Toxoplasma IgG, while 5 (0.28%) tested
      positive for anti-Toxoplasma IgM. The five IgM positive donors had high avidity
      antibodies suggestive of past infection. No active parasitemia was detected by
      real-time PCR assays. Multivariate logistic regression showed that undercooked
      pork meat consumption (adjusted odds ratio [OR] = 2.9; 95% confidence interval
      [CI]: 1.3-6.5), raw mussels consumption (adjusted OR = 5.3; 95% CI: 1.5-19.1),
      having a cat in the household (adjusted OR = 2.0; 95% CI: 1.2-3.2), a lower
      education level (adjusted OR = 1.6; 95% CI: 1.1-2.3), and donation place in
      eastern Taiwan (adjusted OR = 2.5; 95% CI: 1.6-3.9) were independent risk factors
      for Toxoplasma seropositivity. These findings provide information on the
      seroprevalence and epidemiology of T. gondii infection among healthy blood donors
      in Taiwan.

PMID- 23133553
TI  - Combining next-generation sequencing and microarray technology into a
      transcriptomics approach for the non-model organism Chironomus riparius.
AB  - Whole-transcriptome gene-expression analyses are commonly performed in species
      that have a sequenced genome and for which microarrays are commercially
      available. To do such analyses in species with no or limited genome data, i.e.
      non-model organisms, necessary transcriptomics resources, i.e. an annotated
      transcriptome and a validated gene-expression microarray, must first be
      developed. The aim of the present study was to establish an advanced approach for
      developing transcriptomics resources for non-model organisms by combining next
      generation sequencing (NGS) and microarray technology. We applied our approach to
      the non-biting midge Chironomus riparius, an ecologically relevant species that
      is widely used in sediment ecotoxicity testing. We sampled extensively covering
      all C. riparius developmental stages as well as toxicant exposed larvae and
      obtained from a normalized cDNA library 1.5 M NGS reads totalling 501 Mbp. Using
      the NGS data we developed transcriptomics resources in several steps. First, we
      designed 844 k probes directly on the NGS reads, as well as 76 k probes targeting
      expressed sequence tags of related species. These probes were tested for their
      affinity to C. riparius DNA and mRNA, by performing two biological experiments
      with a 1 M probe-selection microarray that contained the entire probe-library.
      Subsequently, the 1.5 M NGS reads were assembled into 23,709 isotigs and 135,082
      singletons, which were associated to ~55 k, respectively, ~61 k gene ontology
      terms and which corresponded together to 22,593 unique protein accessions. An
      algorithm was developed that took the assembly and the probe affinities to DNA
      and mRNA into account, what resulted in 59 k highly-reliable probes that targeted
      uniquely 95% of the isotigs and 18% of the singletons. Concluding, our approach
      allowed the development of high-quality transcriptomics resources for C.
      riparius, and is applicable to any non-model organism. It is expected, that these
      resources will advance ecotoxicity testing with C. riparius as whole
      transcriptome gene-expression analysis are now possible with this species.

PMID- 23133558
TI  - Sensory ecology of water detection by bats: a field experiment.
AB  - Bats face a great risk of dehydration, so sensory mechanisms for water
      recognition are crucial for their survival. In the laboratory, bats recognized
      any smooth horizontal surface as water because these provide analogous
      reflections of echolocation calls. We tested whether bats also approach smooth
      horizontal surfaces other than water to drink in nature by partly covering
      watering troughs used by hundreds of bats with a Perspex layer mimicking water.
      We aimed 1) to confirm that under natural conditions too bats mistake any
      horizontal smooth surface for water by testing this on large numbers of
      individuals from a range of species and 2) to assess the occurrence of learning
      effects. Eleven bat species mistook Perspex for water relying chiefly on
      echoacoustic information. Using black instead of transparent Perspex did not
      deter bats from attempting to drink. In Barbastella barbastellus no echolocation
      differences occurred between bats approaching the water and the Perspex surfaces
      respectively, confirming that bats perceive water and Perspex to be acoustically
      similar. The drinking attempt rates at the fake surface were often lower than
      those recorded in the laboratory: bats then either left the site or moved to the
      control water surface. This suggests that bats modified their behaviour as soon
      as the lack of drinking reward had overridden the influence of echoacoustic
      information. Regardless of which of two adjoining surfaces was covered, bats
      preferentially approached and attempted to drink from the first surface
      encountered, probably because they followed a common route, involving spatial
      memory and perhaps social coordination. Overall, although acoustic recognition
      itself is stereotyped and its importance in the drinking process overwhelming,
      our findings point at the role of experience in increasing behavioural
      flexibility under natural conditions.

PMID- 23133559
TI  - Role of type II protein arginine methyltransferase 5 in the regulation of
      Circadian Per1 gene.
AB  - Circadian clocks are the endogenous oscillators that regulate rhythmic
      physiological and behavioral changes to correspond to daily light-dark cycles.
      Molecular dissections have revealed that transcriptional feedback loops of the
      circadian clock genes drive the molecular oscillation, in which PER/CRY complexes
      inhibit the transcriptional activity of the CLOCK/BMAL1 heterodimer to constitute
      a negative feedback loop. In this study, we identified the type II protein
      arginine methyltransferase 5 (PRMT5) as an interacting molecule of CRY1. Although
      the Prmt5 gene was constitutively expressed, increased interaction of PRMT5 with
      CRY1 was observed when the Per1 gene was repressed both in synchronized mouse
      liver and NIH3T3 cells. Moreover, rhythmic recruitment of PRMT5 and CRY1 to the
      Per1 gene promoter was found to be associated with an increased level of histone
      H4R3 dimethylation and Per1 gene repression. Consistently, decreased histone H4R3
      dimethylation and altered rhythmic Per1 gene expression were observed in Prmt5
      depleted cells. Taken together, these findings provide an insight into the link
      between histone arginine methylation by PRMT5 and transcriptional regulation of
      the circadian Per1 gene.

PMID- 23133560
TI  - Assessing the congruence of thermal niche estimations derived from distribution
      and physiological data. A test using diving beetles.
AB  - A basic aim of ecology is to understand the determinants of organismal
      distribution, the niche concept and species distribution models providing key
      frameworks to approach the problem. As temperature is one of the most important
      factors affecting species distribution, the estimation of thermal limits is
      crucially important for inferring range constraints. It is expectable that
      thermal physiology data derived from laboratory experiments and species'
      occurrences may express different aspects of the species' niche. However, there
      is no study systematically testing this prediction in a given taxonomic group
      while controlling by potential phylogenetic inertia. We estimate the thermal
      niches of twelve Palaearctic diving beetles species using physiological data
      derived from experimental analyses in order to examine the extent to which these
      coincided with those estimated from distribution models based on observed
      occurrences. We found that thermal niche estimates derived from both approaches
      lack general congruence, and these results were similar before and after
      controlling by phylogeny. The congruence between potential distributions obtained
      from the two different procedures was also explored, and we found again that the
      percentage of agreement were not very high (~60%). We confirm that both thermal
      niche estimates derived from geographical and physiological data are likely to
      misrepresent the true range of climatic variation that these diving beetles are
      able to tolerate, and so these procedures could be considered as incomplete but
      complementary estimations of an inaccessible reality.

PMID- 23133561
TI  - Prevalence and risk factors associated with Entamoeba
      histolytica/dispar/moshkovskii infection among three Orang Asli ethnic groups in
      Malaysia.
AB  - BACKGROUND: Entamoeba histolytica/Entamoeba dispar/Entamoeba moshkovskii
      infection is still prevalent in rural Malaysia especially among Orang Asli
      communities. Currently, information on prevalence of this infection among
      different ethnic groups of Orang Asli is unavailable in Malaysia. To contribute
      to a better comprehension of the epidemiology of this infection, a cross
      sectional study aimed at providing the first documented data on the prevalence
      and risk factors associated with E. histolytica/E. dispar/E. moshkovskii
      infection was carried out among three Orang Asli ethnic groups (Proto-Malay,
      Negrito, and Senoi) in selected villages in Negeri Sembilan, Perak, and Pahang
      states, Malaysia. METHODS/FINDINGS: Faecal samples were examined by formalin
      ether sedimentation and trichrome staining techniques. Of 500 individuals, 8.7%
      (13/150) of Proto-Malay, 29.5% (41/139) of Negrito, and 18.5% (39/211) of Senoi
      were positive for E. histolytica/E. dispar/E. moshkovskii, respectively. The
      prevalence of this infection showed an age-dependency relationship, with higher
      rates observed among those aged less than 15 years in all ethnic groups studied.
      Multivariate analysis confirmed that not washing hands after playing with soils
      or gardening and presence of other family members infected with E. histolytica/E.
      dispar/E. moshkovskii were significant risk factors of infection among all ethnic
      groups. However, eating with hands, the consumption of raw vegetables, and close
      contact with domestic animals were identified as significant risk factors in
      Senoi. CONCLUSIONS: Essentially, the findings highlighted that E. histolytica/E.
      dispar/E. moshkovskii parasites are still prevalent in Malaysia. Further studies
      using molecular approaches to distinguish the morphologically identical species
      of pathogenic, E. histolytica from the non-pathogenic, E. dispar and E.
      moshkovskii are needed. The establishment of such data will be beneficial for the
      public health authorities in the planning and implementation of specific
      prevention and control strategies of this infection in different Orang Asli
      ethnic groups in Malaysia.

PMID- 23133562
TI  - In vitro site selection of a consensus binding site for the Drosophila
      melanogaster Tbx20 homolog midline.
AB  - We employed in vitro site selection to identify a consensus binding sequence for
      the Drosophila melanogaster Tbx20 T-box transcription factor homolog Midline. We
      purified a bacterially expressed T-box DNA binding domain of Midline, and used it
      in four rounds of precipitation and polymerase-chain-reaction based
      amplification. We cloned and sequenced 54 random oligonucleotides selected by
      Midline. Electromobility shift-assays confirmed that 27 of these could bind the
      Midline T-box. Sequence alignment of these 27 clones suggests that Midline binds
      as a monomer to a consensus sequence that contains an AGGTGT core. Thus, the
      Midline consensus binding site we define in this study is similar to that defined
      for vertebrate Tbx20, but differs from a previously reported Midline binding
      sequence derived through site selection.

PMID- 23133563
TI  - Significance of heterogeneous Twist2 expression in human breast cancers.
AB  - BACKGROUND: Twist2 (Dermo1) has been shown to mediate the epithelial-mesenchymal
      transition (EMT) to promote tumor invasion and even metastasis. However, the
      involvement of EMT in breast cancer progression is highly debated, partially due
      to clinical observations showing that the majority of human breast carcinoma
      metastases express E-cadherin and maintain their epithelial morphology. The
      molecular mechanism by which Twist2 participates in EMT of breast cancer in vivo
      remains poorly understood. METHODS: We examined Twist2 expression pattern in
      human breast carcinomas by western blot and tissue microarray, and analyzed
      Twist2 cellular localization by confocal microscopy, cell fractionation and other
      approaches. RESULTS: Twist2 expression was significantly increased in breast
      cancer. Cytoplasmic Twist2 positive cancer cells expressing E-cadherin on the
      cellular membrane were mainly located at tumor center of primary carcinomas and
      lymph metastases, while cancer cells with nuclear Twist2 clearly showed loss of E
      cadherin and were detected at the invasive front in ductal breast carcinomas. In
      addition, ectopically stable-expressed Twist2 was found to localize in the
      cytoplasm of cancer cells. Collectively, these data indicate that upregulation of
      cytoplasmic Twist2 is correlated with tumor histological type and tumor
      metastasis in human breast cancers. CONCLUSION: The differential cellular
      distribution of Twist2 may be associated with tumor progression. The cytoplasmic
      Twist2 in cancer cells at tumor center of primary carcinomas and lymph metastases
      contributes to the maintenance of epithelial cancer characteristics expressing E
      cadherin in a noninvasive state, while the nuclear Twist2 at the cancer invasion
      front activates EMT to deprive epithelial property of neoplastic cells, thus
      facilitating invasion and metastasis. These findings suggest that heterogeneous
      expression of Twist2 in tumors may have a functional link to tumor progression.

PMID- 23133564
TI  - Estimating youth locomotion ground reaction forces using an accelerometer-based
      activity monitor.
AB  - To address a variety of questions pertaining to the interactions between physical
      activity, musculoskeletal loading and musculoskeletal health/injury/adaptation,
      simple methods are needed to quantify, outside a laboratory setting, the forces
      acting on the human body during daily activities. The purpose of this study was
      to develop a statistically based model to estimate peak vertical ground reaction
      force (pVGRF) during youth gait. 20 girls (10.9 +/- 0.9 years) and 15 boys (12.5
      +/- 0.6 years) wore a Biotrainer AM over their right hip. Six walking and six
      running trials were completed after a standard warm-up. Average AM intensity (g)
      and pVGRF (N) during stance were determined. Repeated measures mixed effects
      regression models to estimate pVGRF from Biotrainer activity monitor acceleration
      in youth (girls 10-12, boys 12-14 years) while walking and running were
      developed. Log transformed pVGRF had a statistically significant relationship
      with activity monitor acceleration, centered mass, sex (girl), type of locomotion
      (run), and locomotion type-acceleration interaction controlling for subject as a
      random effect. A generalized regression model without subject specific random
      effects was also developed. The average absolute differences between the actual
      and predicted pVGRF were 5.2% (1.6% standard deviation) and 9% (4.2% standard
      deviation) using the mixed and generalized models, respectively. The results of
      this study support the use of estimating pVGRF from hip acceleration using a
      mixed model regression equation.

PMID- 23133565
TI  - Enhanced expression of vacuolar H+-ATPase subunit E in the roots is associated
      with the adaptation of Broussonetia papyrifera to salt stress.
AB  - Vacuolar H(+)-ATPase (V-H(+)-ATPase) may play a pivotal role in maintenance of
      ion homeostasis inside plant cells. In the present study, the expression of V
      H(+)-ATPase genes was analyzed in the roots and leaves of a woody plant,
      Broussonetia papyrifera, which was stressed with 50, 100 and 150 mM NaCl.
      Moreover, the expression and distribution of the subunit E protein were
      investigated by Western blot and immunocytochemistry. These showed that treatment
      of B. papyrifera with NaCl distinctly changed the hydrolytic activity of V-H(+)
      ATPase in the roots and leaves. Salinity induced a dramatic increase in V-H(+)
      ATPase hydrolytic activity in the roots. However, only slight changes in V-H(+)
      ATPase hydrolytic activity were observed in the leaves. In contrast, increased
      H(+) pumping activity of V-H(+)-ATPase was observed in both the roots and leaves.
      In addition, NaCl treatment led to an increase in H(+)-pyrophosphatase (V-H(+)
      PPase) activity in the roots. Moreover, NaCl treatment triggered the enhancement
      of mRNA levels for subunits A, E and c of V-H(+)-ATPase in the roots, whereas
      only subunit c mRNA was observed to increase in the leaves. By Western blot and
      immunocytological analysis, subunit E was shown to be augmented in response to
      salinity stress in the roots. These findings provide evidence that under salt
      stress, increased V-H(+)-ATPase activity in the roots was positively correlated
      with higher transcript and protein levels of V-H(+)-ATPase subunit E. Altogether,
      our results suggest an essential role for V-H(+)-ATPase subunit E in the response
      of plants to salinity stress.

PMID- 23133566
TI  - Transcriptional control of the multi-drug transporter ABCB1 by transcription
      factor Sp3 in different human tissues.
AB  - The ATP-binding cassette (ABC) transporter ABCB1, encoded by the multidrug
      resistance gene MDR1, is expressed on brain microvascular endothelium and several
      types of epithelium, but not on endothelia outside the CNS. It is an essential
      component of the blood-brain barrier. The aim of this study was to identify cell
      specific controls on the transcription of MDR1 in human brain endothelium.
      Reporter assays identified a region of 500 bp around the transcription start site
      that was optimally active in brain endothelium. Chromatin immunoprecipitation
      identified Sp3 and TFIID associated with this region and EMSA (electrophoretic
      mobility shift assays) confirmed that Sp3 binds preferentially to an Sp-target
      site (GC-box) on the MDR1 promoter in brain endothelium. This result contrasts
      with findings in other cell types and with the colon carcinoma line Caco-2, in
      which Sp1 preferentially associates with the MDR1 promoter. Differences in MDR1
      transcriptional control between brain endothelium and Caco-2 could not be
      explained by the relative abundance of Sp1:Sp3 nor by the ratio of Sp3 variants,
      because activating variants of Sp3 were present in both cell types. However
      differential binding of other transcription factors was also detected in two
      additional upstream regions of the MDR1 promoter. Identification of cell-specific
      controls on the transcription of MDR1 indicates that it may be possible to
      modulate multi-drug resistance on tumours, while leaving the blood brain barrier
      intact.

PMID- 23133567
TI  - A cell-based method for screening RNA-protein interactions: identification of
      constitutive transport element-interacting proteins.
AB  - We have developed a mammalian cell-based screening platform to identify proteins
      that assemble into RNA-protein complexes. Based on Tat-mediated activation of the
      HIV LTR, proteins that interact with an RNA target elicit expression of a GFP
      reporter and are captured by fluorescence activated cell sorting. This "Tat
      hybrid" screening platform was used to identify proteins that interact with the
      Mason Pfizer monkey virus (MPMV) constitutive transport element (CTE), a
      structured RNA hairpin that mediates the transport of unspliced viral mRNAs from
      the nucleus to the cytoplasm. Several hnRNP-like proteins, including hnRNP A1,
      were identified and shown to interact with the CTE with selectivity in the
      reporter system comparable to Tap, a known CTE-binding protein. In vitro gel
      shift and pull-down assays showed that hnRNP A1 is able to form a complex with
      the CTE and Tap and that the RGG domain of hnRNP A1 mediates binding to Tap.
      These results suggest that hnRNP-like proteins may be part of larger export
      competent RNA-protein complexes and that the RGG domains of these proteins play
      an important role in directing these binding events. The results also demonstrate
      the utility of the screening platform for identifying and characterizing new
      components of RNA-protein complexes.

PMID- 23133568
TI  - Immunological changes at point-of-lay increase susceptibility to Salmonella
      enterica Serovar enteritidis infection in vaccinated chickens.
AB  - Chicken eggs are the main source of human Salmonella enterica serovar Enteritidis
      infection. S. Enteritidis infects the oviduct and ovary of the chicken leading to
      infection of developing eggs. Therefore, control in poultry production is a major
      public health priority. Vaccination of hens has proved successful in control
      strategies in United Kingdom leading to a 70% drop in human cases since
      introduced. However, as hens reach sexual maturity they become immunosuppressed
      and it has been postulated this leads to increased susceptibility to Salmonella
      infection. In this study we define the changes to the systemic and reproductive
      tract-associated immune system of hens throughout sexual development by flow
      cytometry and histology and determine changes in susceptibility to experimental
      S. Enteritidis challenge in naive and vaccinated hens. Changes to both systemic
      and local immune systems occur in chickens at sexual development around 140 days
      of age. The population of several leukocyte classes drop, with the greatest fall
      in CD4+ lymphocyte numbers. Within the developing reproductive tract there an
      organised structure of lymphocytic aggregates with gammadelta-T lymphocytes
      associated with the mucosa. At point-of-lay, this organised structure disappears
      and only scattered lymphocytes remain. Protection against Salmonella challenge is
      significantly reduced in vaccinated birds at point-of-lay, coinciding with the
      drop in CD4+ lymphocytes. Susceptibility to reproductive tract infection by
      Salmonella increased in vaccinated and naive animals at 140 and 148 days of age.
      We hypothesise that the drop in gammadelta-T lymphocytes in the tract leads to
      decreased innate protection of the mucosa to infection. These findings indicate
      that systemic and local changes to the immune system increase the susceptibility
      of hens to S. Enteritidis infection. The loss of protective immunity in
      vaccinated birds demonstrates that Salmonella control should not rely on
      vaccination alone, but as part of an integrated control strategy including
      biosecurity and improved animal welfare.

PMID- 23133569
TI  - Occurrence of horizontal gene transfer of P(IB)-type ATPase genes among bacteria
      isolated from the uranium rich deposit of Domiasiat in North East India.
AB  - Uranium (U) tolerant aerobic heterotrophs were isolated from the subsurface soils
      of one of the pre-mined U-rich deposits at Domiasiat located in the north-eastern
      part of India. On screening of genomic DNA from 62 isolates exhibiting superior U
      and heavy metal tolerance, 32 isolates were found to be positive for P(IB)-type
      ATPase genes. Phylogenetic incongruence and anomalous DNA base compositions
      revealed the acquisition of P(IB)-type ATPase genes by six isolates through
      horizontal gene transfer (HGT). Three of these instances of HGT appeared to have
      occurred at inter-phylum level and the other three instances indicated to have
      taken place at intra-phylum level. This study provides an insight into one of the
      possible survival strategies that bacteria might employ to adapt to environments
      rich in uranium and heavy metals.

PMID- 23133570
TI  - Tradeoffs in the evolution of caste and body size in the hyperdiverse ant genus
      Pheidole.
AB  - The efficient investment of resources is often the route to ecological success,
      and the adaptability of resource investment may play a critical role in promoting
      biodiversity. The ants of the "hyperdiverse" genus Pheidole produce two discrete
      sterile castes, soldiers and minor workers. Within Pheidole, there is tremendous
      interspecific variation in proportion of soldiers. The causes and correlates of
      caste ratio variation among species of Pheidole remain enigmatic. Here we test
      whether a body size threshold model accounts for interspecific variation in caste
      ratio in Pheidole, such that species with larger body sizes produce relatively
      fewer soldiers within their colonies. We evaluated the caste ratio of 26 species
      of Pheidole and found that the body size of workers accounts for interspecific
      variation in the production of soldiers as we predicted. Twelve species sampled
      from one forest in Costa Rica yielded the same relationship as found in
      previously published data from many localities. We conclude that production of
      soldiers in the most species-rich group of ants is regulated by a body size
      threshold mechanism, and that the great variation in body size and caste ratio in
      Pheidole plays a role in niche divergence in this rapidly evolving taxon.

PMID- 23133571
TI  - Perturbations in histidine biosynthesis uncover robustness in the metabolic
      network of Salmonella enterica.
AB  - Phosphoribosylamine (PRA) is an intermediate in the biosynthetic pathway that is
      common to thiamine and purines. Glutamine phosphoribosyl pyrophosphate (PRPP)
      amidotransferase is the product of the purF gene in Salmonella enterica and
      catalyzes the synthesis of PRA from PRPP and glutamine. Strains lacking PurF
      require exogenous addition of purines for growth. However, under some growth
      conditions or with specific secondary mutations these strains grow in the absence
      of exogenous thiamine. Mutant alleles of hisA, which encodes 1-(5-phosphoribosyl)
      5-[(5-phosphoribosylamino) methylideneamino] imidazole-4-carboxamide (ProFAR)
      isomerase, allowed PurF-independent PRA formation. The alleles of hisA that
      suppressed the requirement for exogenous thiamine resulted in proteins with
      reduced enzymatic activity. Data presented here showed that decreased activity of
      HisA altered metabolite pools and allowed PRA formation from ProFAR. Possible
      mechanisms of this conversion were proposed. The results herein emphasize the
      plasticity of the metabolic network and specifically highlight the potential for
      chemical syntheses to contribute to network robustness.

PMID- 23133572
TI  - Genome-wide association study to identify the genetic determinants of otitis
      media susceptibility in childhood.
AB  - BACKGROUND: Otitis media (OM) is a common childhood disease characterised by
      middle ear inflammation and effusion. Susceptibility to recurrent acute OM (rAOM;
      >= 3 episodes of AOM in 6 months) and chronic OM with effusion (COME; MEE >= 3
      months) is 40-70% heritable. Few underlying genes have been identified to date,
      and no genome-wide association study (GWAS) of OM has been reported. METHODS AND
      FINDINGS: Data for 2,524,817 single nucleotide polymorphisms (SNPs; 535,544
      quality-controlled SNPs genotyped by Illumina 660W-Quad; 1,989,273 by imputation)
      were analysed for association with OM in 416 cases and 1,075 controls from the
      Western Australian Pregnancy Cohort (Raine) Study. Logistic regression analyses
      under an additive model undertaken in GenABEL/ProbABEL adjusting for population
      substructure using principal components identified SNPs at CAPN14 (rs6755194: OR
      = 1.90; 95%CI 1.47-2.45; P(adj-PCA) = 8.3 * 10(-7)) on chromosome 2p23.1 as the
      top hit, with independent effects (rs1862981: OR = 1.60; 95%CI 1.29-1.99; P(adj
      PCA) = 2.2 * 10(-5)) observed at the adjacent GALNT14 gene. In a gene-based
      analysis in VEGAS, BPIFA3 (P(Gene) = 2 * 10(-5)) and BPIFA1 (P(Gene) = 1.07 * 10(
      4)) in the BPIFA gene cluster on chromosome 20q11.21 were the top hits. In all,
      32 genomic regions show evidence of association (P(adj-PCA)<10(-5)) in this GWAS,
      with pathway analysis showing a connection between top candidates and the TGFbeta
      pathway. However, top and tag-SNP analysis for seven selected candidate genes in
      this pathway did not replicate in 645 families (793 affected individuals) from
      the Western Australian Family Study of Otitis Media (WAFSOM). Lack of replication
      may be explained by sample size, difference in OM disease severity between
      primary and replication cohorts or due to type I error in the primary GWAS.
      CONCLUSIONS: This first discovery GWAS for an OM phenotype has identified CAPN14
      and GALNT14 on chromosome 2p23.1 and the BPIFA gene cluster on chromosome
      20q11.21 as novel candidate genes which warrant further analysis in cohorts
      matched more precisely for clinical phenotypes.

PMID- 23133573
TI  - Prevalence and factors associated with hepatitis B immunization and infection
      among men who have sex with men in Beijing, China.
AB  - BACKGROUND: Among the Chinese population of 1.3 billion, there are an estimated
      93 million carriers of hepatitis B virus (HBV). Men who have sex with men (MSM)
      are at increased risk for HBV infection; however, the prevalence of HBV
      immunization and infection among Chinese MSM remains undetermined. METHODS: A
      cross-sectional survey of 1,114 eligible participants was conducted in Beijing,
      China. Multiple methods were used to recruit study participants. Demographic
      information and potential correlated factors were collected by questionnaire.
      Additionally, blood specimens were collected and tested for sexually transmitted
      infections and serologic markers of hepatitis B immunization and infection.
      RESULTS: Laboratory data were available for 1,111 participants (99.7%), the
      prevalence of hepatitis B immunization was 38.9%, and 26.5% had serologic markers
      of HBV infection. Multivariate analyses indicated that higher education level,
      smaller number of male sex partners in the past 12 months, reported diagnosis of
      sexually transmitted disease (STD), and history of blood donation were
      independently associated with HBV immunization. Absence of steady male sex
      partner(s) in the past 12 months, and reported diagnosis of STD were shown to be
      independently associated with HBV infection. MSM positive for HBV infection were
      more likely to have past or current syphilis infection. CONCLUSIONS: Low
      prevalence of HBV immunization and high prevalence of HBV infection among Chinese
      MSM and a correlation between sexual risk factors and hepatitis B infection
      indicate that comprehensive preventative measures for HBV among MSM, including
      blood donor and HIV-STD clinic vaccination programs as well as targeted health
      education campaigns should be developed in China.

PMID- 23133574
TI  - Increased biomass yield of Lactococcus lactis by reduced overconsumption of amino
      acids and increased catalytic activities of enzymes.
AB  - Steady state cultivation and multidimensional data analysis (metabolic fluxes,
      absolute proteome, and transcriptome) are used to identify parameters that
      control the increase in biomass yield of Lactococcus lactis from 0.10 to 0.12 C
      mol C-mol(-1) with an increase in specific growth rate by 5 times from 0.1 to 0.5
      h(-1). Reorganization of amino acid consumption was expressed by the inactivation
      of the arginine deiminase pathway at a specific growth rate of 0.35 h(-1)
      followed by reduced over-consumption of pyruvate directed amino acids
      (asparagine, serine, threonine, alanine and cysteine) until almost all consumed
      amino acids were used only for protein synthesis at maximal specific growth rate.
      This balanced growth was characterized by a high glycolytic flux carrying up to
      87% of the carbon flow and only amino acids that relate to nucleotide synthesis
      (glutamine, serine and asparagine) were consumed in higher amounts than required
      for cellular protein synthesis. Changes in the proteome were minor (mainly
      increase in the translation apparatus). Instead, the apparent catalytic
      activities of enzymes and ribosomes increased by 3.5 times (0.1 vs 0.5 h(-1)).
      The apparent catalytic activities of glycolytic enzymes and ribosomal proteins
      were seen to follow this regulation pattern while those of enzymes involved in
      nucleotide metabolism increased more than the specific growth rate (over 5.5
      times). Nucleotide synthesis formed the most abundant biomonomer synthetic
      pathway in the cells with an expenditure of 6% from the total ATP required for
      biosynthesis. Due to the increase in apparent catalytic activity, ribosome
      translation was more efficient at higher growth rates as evidenced by a decrease
      of protein to mRNA ratios. All these effects resulted in a 30% decrease of
      calculated ATP spilling (0.1 vs 0.5 h(-1)). Our results show that bioprocesses
      can be made more efficient (using a balanced metabolism) by varying the growth
      conditions.

PMID- 23133575
TI  - Proteomic properties reveal phyloecological clusters of Archaea.
AB  - In this study, we propose a novel way to describe the variety of environmental
      adaptations of Archaea. We have clustered 57 Archaea by using a non-redundant set
      of proteomic features, and verified that the clusters correspond to environmental
      adaptations to the archaeal habitats. The first cluster consists dominantly of
      hyperthermophiles and hyperthermoacidophilic aerobes. The second cluster joins
      together halophilic and extremely halophilic Archaea, while the third cluster
      contains mesophilic (mostly methanogenic) Archaea together with
      thermoacidophiles. The non-redundant subset of proteomic features was found to
      consist of five features: the ratio of charged residues to uncharged, average
      protein size, normalized frequency of beta-sheet, normalized frequency of
      extended structure and number of hydrogen bond donors. We propose this clustering
      to be termed phyloecological clustering. This approach could give additional
      insights into relationships among archaeal species that may be hidden by sole
      phylogenetic analysis.

PMID- 23133576
TI  - 2-Hydroxyoleic acid induces ER stress and autophagy in various human glioma cell
      lines.
AB  - BACKGROUND: 2-Hydroxyoleic acid is a synthetic fatty acid with potent anti-cancer
      activity which does not induce undesired side effects. However, the molecular and
      cellular mechanisms by which this compound selectively kills human glioma cancer
      cells without killing normal cells is not fully understood. The present study was
      designed to determine the molecular bases underlying the potency against 1321N1,
      SF-767 and U118 human glioma cell lines growth without affecting non cancer MRC-5
      cells. METHODOLOGY/PRINCIPAL FINDINGS: The cellular levels of endoplasmic
      reticulum (ER) stress, unfolded protein response (UPR) and autophagy markers were
      determined by quantitative RT-PCR and immunoblotting on 1321N1, SF-767 and U118
      human glioma cells and non-tumor MRC-5 cells incubated in the presence or absence
      of 2OHOA or the ER stress/autophagy inducer, palmitate. The cellular response to
      these agents was evaluated by fluorescence microscopy, electron microscopy and
      flow cytometry. We have observed that 2OHOA treatments induced augments in the
      expression of important ER stress/UPR markers, such as phosphorylated eIF2alpha,
      IRE1alpha, CHOP, ATF4 and the spliced form of XBP1 in human glioma cells.
      Concomitantly, 2OHOA led to the arrest of 1321N1 cells in the G(2)/M phase of the
      cell cycle, with down-regulation of cyclin B1 and Cdk1/Cdc2 proteins in the three
      glioma cell lines studied. Finally, 2OHOA induced autophagy in 1321N1, SF-767 and
      U118 cells, with the appearance of autophagic vesicles and the up-regulation of
      LC3BI, LC3BII and ATG7 in 1321N1 cells, increases of LC3BI, LC3BII and ATG5 in SF
      767 cells and up-regulation of LC3BI and LC3BII in U118 cells. Importantly, 2OHOA
      failed to induce such changes in non-tumor MRC-5 cells. CONCLUSION/SIGNIFICANCE:
      The present results demonstrate that 2OHOA induces ER stress/UPR and autophagy in
      human glioma (1321N1, SF-767 and U118 cell lines) but not normal (MRC-5) cells,
      unraveling the molecular bases underlying the efficacy and lack of toxicity of
      this compound.

PMID- 23133577
TI  - Differential evolution of MAGE genes based on expression pattern and selection
      pressure.
AB  - Starting from publicly-accessible datasets, we have utilized comparative and
      phylogenetic genome analyses to characterize the evolution of the human MAGE gene
      family. Our characterization of genomic structures in representative genomes of
      primates, rodents, carnivora, and macroscelidea indicates that both Type I and
      Type II MAGE genes have undergone lineage-specific evolution. The restricted
      expression pattern in germ cells of Type I MAGE orthologs is observed throughout
      evolutionary history. Unlike Type II MAGEs that have conserved promoter
      sequences, Type I MAGEs lack promoter conservation, suggesting that epigenetic
      regulation is a central mechanism for controlling their expression. Codon
      analysis shows that Type I but not Type II MAGE genes have been under positive
      selection. The combination of genomic and expression analysis suggests that Type
      1 MAGE promoters and genes continue to evolve in the hominin lineage, perhaps
      towards functional diversification or acquiring additional specific functions,
      and that selection pressure at codon level is associated with expression
      spectrum.

PMID- 23133578
TI  - Self-assembling complexes of quantum dots and scFv antibodies for cancer cell
      targeting and imaging.
AB  - Semiconductor quantum dots represent a novel class of fluorophores with unique
      physical and chemical properties which could enable a remarkable broadening of
      the current applications of fluorescent imaging and optical diagnostics.
      Complexes of quantum dots and antibodies are promising visualising agents for
      fluorescent detection of selective biomarkers overexpressed in tumor tissues.
      Here we describe the construction of self-assembling fluorescent complexes of
      quantum dots and anti-HER1 or anti-HER2/neu scFv antibodies and their
      interactions with cultured tumor cells. A binding strategy based on a very
      specific non-covalent interaction between two proteins, barnase and barstar, was
      used to connect quantum dots and the targeting antibodies. Such a strategy allows
      combining the targeting and visualization functions simply by varying the
      corresponding modules of the fluorescent complex.

PMID- 23133579
TI  - Extracellular localization of the diterpene sclareol in clary sage (Salvia
      sclarea L., Lamiaceae).
AB  - Sclareol is a high-value natural product obtained by solid/liquid extraction of
      clary sage (Salvia sclarea L.) inflorescences. Because processes of excretion and
      accumulation of this labdane diterpene are unknown, the aim of this work was to
      gain knowledge on its sites of accumulation in planta. Samples were collected in
      natura or during different steps of the industrial process of extraction (steam
      distillation and solid/liquid extraction). Samples were then analysed with a
      combination of complementary analytical techniques (gas chromatography coupled to
      a mass spectrometer, polarized light microscopy, environmental scanning electron
      microscopy, two-photon fluorescence microscopy, second harmonic generation
      microscopy). According to the literature, it is hypothesized that sclareol is
      localized in oil pockets of secretory trichomes. This study demonstrates that
      this is not the case and that sclareol accumulates in a crystalline epicuticular
      form, mostly on calyces.

PMID- 23133580
TI  - Comparing molecular methods for early detection and serotyping of enteroviruses
      in throat swabs of pediatric patients.
AB  - BACKGROUND: Enteroviruses include over 100 serotypes and usually cause self
      limited infections with non-specific symptoms in children, with the exceptions of
      polioviruses and enterovirus 71 which frequently cause neurologic complications.
      Therefore, early detection and serotyping of enteroviruses are critical in
      clinical management and disease surveillance. Traditional methods for detection
      and serotyping of enteroviruses are virus isolation and immunofluorescence assay,
      which are time-consuming. In this study, we compare virus isolation and two
      molecular tests for detection and serotyping of enteroviruses in clinical
      samples. METHODS: One hundred and ten throat swabs were collected from pediatric
      outpatients with enterovirus-like illnesses (hand-foot-mouth disease, herpangina,
      and non-specific febrile illness). Virus isolation was conducted using multiple
      cell lines and isolated viruses were serotyped using immunofluorescent assay. In
      the molecular tests, a semi-nested RT-PCR and a novel CODEHOP platform were used
      to detect the 5'UTR and VP1 genes of enteroviruses, respectively. Amplified
      nucleotides were sequenced and genotyped. RESULTS: Among the 110 cases, 39(35%),
      52(47%), and 46(42%) were tested positive with these three tests, respectively.
      Using the consensus results of these three tests as the gold standard, agreement
      of the VP1 CODEHOP test was 96%, which is higher than those of the virus
      isolation (89%) and the 5'-UTR test (88%). The VP1 CODEHOP test also has the best
      performance on serotyping confirmed with serum neutralization tests. CONCLUSIONS:
      The VP1 CODEHOP test performed well for detection and serotyping of enteroviruses
      in clinical specimens and could reduce unnecessary hospitalization cares during
      enterovirus seasons.

PMID- 23133581
TI  - Reconstruction and comparison of the metabolic potential of cyanobacteria
      Cyanothece sp. ATCC 51142 and Synechocystis sp. PCC 6803.
AB  - Cyanobacteria are an important group of photoautotrophic organisms that can
      synthesize valuable bio-products by harnessing solar energy. They are endowed
      with high photosynthetic efficiencies and diverse metabolic capabilities that
      confer the ability to convert solar energy into a variety of biofuels and their
      precursors. However, less well studied are the similarities and differences in
      metabolism of different species of cyanobacteria as they pertain to their
      suitability as microbial production chassis. Here we assemble, update and compare
      genome-scale models (iCyt773 and iSyn731) for two phylogenetically related
      cyanobacterial species, namely Cyanothece sp. ATCC 51142 and Synechocystis sp.
      PCC 6803. All reactions are elementally and charge balanced and localized into
      four different intracellular compartments (i.e., periplasm, cytosol, carboxysome
      and thylakoid lumen) and biomass descriptions are derived based on experimental
      measurements. Newly added reactions absent in earlier models (266 and 322,
      respectively) span most metabolic pathways with an emphasis on lipid
      biosynthesis. All thermodynamically infeasible loops are identified and
      eliminated from both models. Comparisons of model predictions against gene
      essentiality data reveal a specificity of 0.94 (94/100) and a sensitivity of 1
      (19/19) for the Synechocystis iSyn731 model. The diurnal rhythm of Cyanothece
      51142 metabolism is modeled by constructing separate (light/dark) biomass
      equations and introducing regulatory restrictions over light and dark phases.
      Specific metabolic pathway differences between the two cyanobacteria alluding to
      different bio-production potentials are reflected in both models.

PMID- 23133582
TI  - Young children are more generous when others are aware of their actions.
AB  - Adults frequently employ reputation-enhancing strategies when engaging in
      prosocial acts, behaving more generously when their actions are likely to be
      witnessed by others and even more so when the extent of their generosity is made
      public. This study examined the developmental origins of sensitivity to cues
      associated with reputationally motivated prosociality by presenting five-year
      olds with the option to provide one or four stickers to a familiar peer recipient
      at no cost to themselves. We systematically manipulated the recipient's knowledge
      of the actor's choices in two different ways: (1) occluding the recipient's view
      of both the actor and the allocation options and (2) presenting allocations in
      opaque containers whose contents were visible only to the actor. Children were
      consistently generous only when the recipient was fully aware of the donation
      options; in all cases in which the recipient was not aware of the donation
      options, children were strikingly ungenerous. These results demonstrate that five
      year-olds exhibit "strategic prosociality," behaving differentially generous as a
      function of the amount of information available to the recipient about their
      actions. These findings suggest that long before they develop a rich
      understanding of the social significance of reputation or are conscious of
      complex strategic reasoning, children behave more generously when the details of
      their prosocial actions are available to others.

PMID- 23133583
TI  - Depressive symptoms are not associated with leukocyte telomere length: findings
      from the Nova Scotia Health Survey (NSHS95), a population-based study.
AB  - BACKGROUND: Premature shortening of leukocyte telomere length has been proposed
      as a novel mechanism by which depression may confer increased risk of adverse
      cardiovascular events. Prior studies demonstrating associations of depression and
      depressive symptoms with shorter leukocyte telomere length were small, included
      selected psychiatric outpatients, were based on convenience samples, and/or
      adjusted for a limited number of possible confounding factors. METHODS AND
      FINDINGS: We examined the associations of depressive symptoms, probable
      depressive disorder, and specific depressive symptom clusters, as assessed by the
      Center for Epidemiological Studies--Depression (CES-D) scale, with leukocyte
      telomere length, measured by using a real-time PCR method, in 2,225 apparently
      healthy participants from the 1995 Nova Scotia Health Survey population-based
      study. The mean age was 48.2 +/- 18.9 years; 49.9% of participants were female;
      and the mean CES-D score was 7.4 +/- 7.9. The mean telomere length was 5,301 +/-
      587 base pairs. In an unadjusted model, depressive symptoms were significantly
      associated with longer leukocyte telomere length (B = 27.6 base pairs per
      standard deviation increase in CES-D, 95% confidence interval [CI] = 3.1-52.1, p
      = 0.027). This association was no longer significant after adjustment for age and
      sex (B = 9.5, 95% CI = -14.6-33.6, p = 0.44) or after further adjustment for body
      mass index, Framingham risk score and previous history of ischemic heart disease
      (all p's >= 0.37). Neither probable depressive disorder nor specific depressive
      symptom clusters were independently associated with leukocyte telomere length.
      CONCLUSIONS: Concurrent depressive symptoms were not associated with leukocyte
      telomere length in a large, representative, population-based study.

PMID- 23133584
TI  - Aberrant community architecture and attenuated persistence of uropathogenic
      Escherichia coli in the absence of individual IHF subunits.
AB  - Uropathogenic Escherichia coli (UPEC) utilizes a complex community-based
      developmental pathway for growth within superficial epithelial cells of the
      bladder during cystitis. Extracellular DNA (eDNA) is a common matrix component of
      organized bacterial communities. Integration host factor (IHF) is a heterodimeric
      protein that binds to double-stranded DNA and produces a hairpin bend. IHF
      dependent DNA architectural changes act both intrabacterially and
      extrabacterially to regulate gene expression and community stability,
      respectively. We demonstrate that both IHF subunits are required for efficient
      colonization of the bladder, but are dispensable for early colonization of the
      kidney. The community architecture of the intracellular bacterial communities
      (IBCs) is quantitatively different in the absence of either IhfA or IhfB in the
      murine model for human urinary tract infection (UTI). Restoration of Type 1 pili
      by ectopic production does not restore colonization in the absence of IhfA, but
      partially compensates in the absence of IhfB. Furthermore, we describe a binding
      site for IHF that is upstream of the operon that encodes for the P-pilus. Taken
      together, these data suggest that both IHF and its constituent subunits
      (independent of the heterodimer), are able to participate in multiple aspects of
      the UPEC pathogenic lifestyle, and may have utility as a target for treatment of
      bacterial cystitis.

PMID- 23133585
TI  - Reduction of Prep1 levels affects differentiation of normal and malignant B cells
      and accelerates Myc driven lymphomagenesis.
AB  - The Prep1 homeodomain transcription factor has recently been recognized as a
      tumor suppressor. Among other features, haploinsufficiency of Prep1 is able to
      strongly accelerate the B-lymphomagenesis in EMUMyc mice. Now we report that this
      occurs concomitantly with a change in the type of B-cell lymphomas generated by
      the Myc oncogene. Indeed, the tumors generated in the EMUMyc-Prep1(+/-) mice are
      much more immature, being mostly made up of Pro-B or Pre-B cells, while those in
      the EMUMyc-Prep1(+/+) mice are more differentiated being invariably IgM(+).
      Moreover, we show that Prep1 is in fact required for the differentiation of Pro-B
      and Pre-B cells into IgM(+) lymphocytes and/or their proliferation, thus showing
      also how a normal function of Prep1 affects EMUMyc lymphomagenesis. Finally, we
      show that the haploinsufficiency of Prep1 is accompanied with a major decrease of
      Myc-induced apoptosis and that the haploinsufficieny is sufficient for all these
      effects because the second allele of Prep1 is not lost even at late stages.
      Therefore, the tumor-suppressive activity of Prep1 is intertwined with both the
      interference with Myc-induced apoptosis as well as with natural developmental
      functions of the protein.

PMID- 23133586
TI  - Site saturation mutagenesis demonstrates a central role for cysteine 298 as
      proton donor to the catalytic site in CaHydA [FeFe]-hydrogenase.
AB  - [FeFe]-hydrogenases reversibly catalyse molecular hydrogen evolution by reduction
      of two protons. Proton supply to the catalytic site (H-cluster) is essential for
      enzymatic activity. Cysteine 298 is a highly conserved residue in all [FeFe]
      hydrogenases; moreover C298 is structurally very close to the H-cluster and it is
      important for hydrogenase activity. Here, the function of C298 in catalysis was
      investigated in detail by means of site saturation mutagenesis, simultaneously
      studying the effect of C298 replacement with all other 19 amino acids and
      selecting for mutants with high retained activity. We demonstrated that efficient
      enzymatic turnover was maintained only when C298 was replaced by aspartic acid,
      despite the structural diversity between the two residues. Purified CaHydA C298D
      does not show any significant structural difference in terms of secondary
      structure and iron incorporation, demonstrating that the mutation does not affect
      the overall protein fold. C298D retains the hydrogen evolution activity with a
      decrease of k(cat) only by 2-fold at pH 8.0 and it caused a shift of the optimum
      pH from 8.0 to 7.0. Moreover, the oxygen inactivation rate was not affected
      demonstrating that the mutation does not influence O(2) diffusion to the active
      site or its reactivity with the H-cluster. Our results clearly demonstrate that,
      in order to maintain the catalytic efficiency and the high turnover number
      typical of [FeFe] hydrogenases, the highly conserved C298 can be replaced only by
      another ionisable residue with similar steric hindrance, giving evidence of its
      involvement in the catalytic function of [FeFe]-hydrogenases in agreement with an
      essential role in proton transfer to the active site.

PMID- 23133587
TI  - A single residue substitution in the receptor-binding domain of H5N1
      hemagglutinin is critical for packaging into pseudotyped lentiviral particles.
AB  - BACKGROUND: Serological studies for influenza infection and vaccine response
      often involve microneutralization and hemagglutination inhibition assays to
      evaluate neutralizing antibodies against human and avian influenza viruses,
      including H5N1. We have previously characterized lentiviral particles pseudotyped
      with H5-HA (H5pp) and validated an H5pp-based assay as a safe alternative for
      high-throughput serological studies in BSL-2 facilities. Here we show that H5-HAs
      from different clades do not always give rise to efficient production of H5pp and
      the underlying mechanisms are addressed. METHODOLOGY/FINDINGS: We have carried
      out mutational analysis to delineate the molecular determinants responsible for
      efficient packaging of HA from A/Cambodia/40808/2005 (H5Cam) and A/Anhui/1/2005
      (H5Anh) into H5pp. Our results demonstrate that a single A134V mutation in the
      130-loop of the receptor binding domain is sufficient to render H5Anh the ability
      to generate H5Anh-pp efficiently, whereas the reverse V134A mutation greatly
      hampers production of H5Cam-pp. Although protein expression in total cell lysates
      is similar for H5Anh and H5Cam, cell surface expression of H5Cam is detected at a
      significantly higher level than that of H5Anh. We further demonstrate by several
      independent lines of evidence that the behaviour of H5Anh can be explained by a
      stronger binding to sialic acid receptors implicating residue 134. CONCLUSIONS:
      We have identified a single A134V mutation as the molecular determinant in H5-HA
      for efficient incorporation into H5pp envelope and delineated the underlying
      mechanism. The reduced binding to sialic acid receptors as a result of the A134V
      mutation not only exerts a critical influence in pseudotyping efficiency of H5
      HA, but has also an impact at the whole virus level. Because A134V substitution
      has been reported as a naturally occurring mutation in human host, our results
      may have implications for the understanding of human host adaptation of avian
      influenza H5N1 viruses.

PMID- 23133588
TI  - Online medical literature consultation habits of academic teaching physicians in
      the EU and CIS countries: a cross-sectional study.
AB  - BACKGROUND: Both in the Commonwealth of Independent States (CIS) and in the
      European Union (EU2004), ample availability of up to date medical scientific
      literature is important for progress in medical science and for the education of
      the next generation of healthcare workers. The aim of this research is to assess
      if the use of online medical literature among academic teaching (AT) physicians
      is at the same level in the CIS as in the EU2004. METHODOLOGY/PRINCIPAL FINDINGS:
      In the capital cities of the CIS and the EU2004 member states, AT physicians
      holding an academic position at least equivalent to an associate professor and
      performing the three classical tasks in academic medicine (teaching, research and
      patient care) were interviewed about their use of and familiarity with the
      Internet and 9 online literature services, including journals and bibliographical
      databases such as PubMed (Medline), The Cochrane Library and Web of Science.
      Library staff members were interviewed about the availability of these online
      literature services at their libraries. About 750 physicians and 40 library staff
      members were invited for participation. Eventually 124 AT physicians and 22
      library staff members participated. Internet was everywhere available, but used
      daily by more AT physicians in the EU2004 (71% versus 48% in the CIS, P = .005).
      AT physicians in the EU2004 accessed a higher percentage of all articles online
      (74% versus 43% in the CIS, P<.001). PubMed (P<.001), The Cochrane Library
      (P<.001) and Web of Science (P<.003) were used more frequently in the EU2004. In
      the EU2004 more AT physicians were familiar with Open Access journals (89% versus
      51% in the CIS, P<.001). CONCLUSIONS/SIGNIFICANCE: AT physicians in the CIS use
      online medical literature less than in the EU2004. It is recommended that the
      awareness of freely available online literature services such as Open Access
      journals is enhanced among AT physicians and library staff members, especially in
      the CIS.

PMID- 23133590
TI  - A framework for regularized non-negative matrix factorization, with application
      to the analysis of gene expression data.
AB  - Non-negative matrix factorization (NMF) condenses high-dimensional data into
      lower-dimensional models subject to the requirement that data can only be added,
      never subtracted. However, the NMF problem does not have a unique solution,
      creating a need for additional constraints (regularization constraints) to
      promote informative solutions. Regularized NMF problems are more complicated than
      conventional NMF problems, creating a need for computational methods that
      incorporate the extra constraints in a reliable way. We developed novel methods
      for regularized NMF based on block-coordinate descent with proximal point
      modification and a fast optimization procedure over the alpha simplex. Our
      framework has important advantages in that it (a) accommodates for a wide range
      of regularization terms, including sparsity-inducing terms like the L1 penalty,
      (b) guarantees that the solutions satisfy necessary conditions for optimality,
      ensuring that the results have well-defined numerical meaning, (c) allows the
      scale of the solution to be controlled exactly, and (d) is computationally
      efficient. We illustrate the use of our approach on in the context of gene
      expression microarray data analysis. The improvements described remedy key
      limitations of previous proposals, strengthen the theoretical basis of
      regularized NMF, and facilitate the use of regularized NMF in applications.

PMID- 23133589
TI  - Bitter taste receptor polymorphisms and human aging.
AB  - Several studies have shown that genetic factors account for 25% of the variation
      in human life span. On the basis of published molecular, genetic and
      epidemiological data, we hypothesized that genetic polymorphisms of taste
      receptors, which modulate food preferences but are also expressed in a number of
      organs and regulate food absorption processing and metabolism, could modulate the
      aging process. Using a tagging approach, we investigated the possible
      associations between longevity and the common genetic variation at the three
      bitter taste receptor gene clusters on chromosomes 5, 7 and 12 in a population of
      941 individuals ranging in age from 20 to 106 years from the South of Italy. We
      found that one polymorphism, rs978739, situated 212 bp upstream of the TAS2R16
      gene, shows a statistically significant association (p = 0.001) with longevity.
      In particular, the frequency of A/A homozygotes increases gradually from 35% in
      subjects aged 20 to 70 up to 55% in centenarians. These data provide suggestive
      evidence on the possible correlation between human longevity and taste genetics.

PMID- 23133591
TI  - The effect of chance variability in blood pressure readings on the decision
      making of general practitioners: an internet-based case vignette study.
AB  - BACKGROUND: Guidelines for the management of blood pressure (BP) in primary care
      generally suggest that decisions be made on the basis of specific threshold
      values (e.g. BP 140/90 mmHg); but this fails to adequately accommodate a common
      cause of variation--the play of chance. OBJECTIVE: To determine the impact of
      chance variability in BP readings on the clinical decision making of general
      practitioners (GPs) regarding anti-hypertensive treatment and cardiovascular risk
      management. METHOD: We used an internet based study design, where 109 GPs were
      assigned to manage one of eight case vignettes (guidelines would recommend
      treatment for only one of the eight) and presented with blood pressure readings
      that were randomly selected from an underlying population. RESULTS: Seventeen
      (15.6%, 17/109) GPs consulted the vignette for whom treatment was recommended,
      but only 7/17 (41.2%) GPs prescribed treatment, whereas 14/92 (15.2%) GPs
      prescribed medication to the other vignettes. When deciding to follow-up a
      vignette GPs were influenced by threshold values for systolic and diastolic BP,
      but not by the overall cardiovascular risk. If the first reading was a low BP
      (systolic <140, diastolic <90) GPs were highly likely to discharge the vignette
      and follow-up a high BP reading (diastolic >90 or systolic BP>=140). Similar
      factors predicted the decision to prescribe a drug, although the vignette's
      cardiovascular risk (>20%) was now statistically significant (p = 0.03).
      CONCLUSIONS: GP decision making, whilst generally consistent with guidelines,
      appears to be compromised by chance variation leading to under and over
      treatment. Interventions to adequately accommodate chance variability into
      clinical decision making are required.

PMID- 23133592
TI  - Pregnancy induces transcriptional activation of the peripheral innate immune
      system and increases oxidative DNA damage among healthy third trimester pregnant
      women.
AB  - BACKGROUND: Pregnancy induces physiological adaptations that may involve, or
      contribute to, alterations in the genomic landscape. Pregnancy also increases the
      nutritional demand for choline, an essential nutrient that can modulate
      epigenomic and transcriptomic readouts secondary to its role as a methyl donor.
      Nevertheless, the interplay between human pregnancy, choline and the human genome
      is largely unexplored. METHODOLOGY/PRINCIPAL FINDINGS: As part of a controlled
      feeding study, we assessed the influence of pregnancy and choline intake on
      maternal genomic markers. Healthy third trimester pregnant (n = 26, wk 26-29
      gestation) and nonpregnant (n = 21) women were randomized to choline intakes of
      480 mg/day, approximating the Adequate Intake level, or 930 mg/day for 12-weeks.
      Blood leukocytes were acquired at study week 0 and study week 12 for microarray,
      DNA damage and global DNA/histone methylation measurements. A main effect of
      pregnancy that was independent of choline intake was detected on several of the
      maternal leukocyte genomic markers. Compared to nonpregnant women, third
      trimester pregnant women exhibited higher (P<0.05) transcript abundance of
      defense response genes associated with the innate immune system including pattern
      recognition molecules, neutrophil granule proteins and oxidases, complement
      proteins, cytokines and chemokines. Pregnant women also exhibited higher
      (P<0.001) levels of DNA damage in blood leukocytes, a genomic marker of oxidative
      stress. No effect of choline intake was detected on the maternal leukocyte
      genomic markers with the exception of histone 3 lysine 4 di-methylation which was
      lower among pregnant women in the 930 versus 480 mg/d choline intake group.
      CONCLUSIONS: Pregnancy induces transcriptional activation of the peripheral
      innate immune system and increases oxidative DNA damage among healthy third
      trimester pregnant women.

PMID- 23133593
TI  - Conformations of islet amyloid polypeptide monomers in a membrane environment:
      implications for fibril formation.
AB  - The amyloid fibrils formed by islet amyloid polypeptide (IAPP) are associated
      with type II diabetes. One of the proposed mechanisms of the toxicity of IAPP is
      that it causes membrane damage. The fatal mutation of S20G human IAPP was
      reported to lead to early onset of type II diabetes and high tendency of amyloid
      formation in vitro. Characterizing the structural features of the S20G mutant in
      its monomeric state is experimentally difficult because of its unusually fast
      aggregation rate. Computational work complements experimental studies. We
      performed a series of molecular dynamics simulations of the monomeric state of
      human variants in the membrane. Our simulations are validated by extensive
      comparisons with experimental data. We find that a helical disruption at His18 is
      common to both human variants. An L-shaped motif of S20G mutant is observed in
      one of the conformational families. This motif that bends at His18 resembles the
      overall topology of IAPP fibrils. The conformational preorganization into the
      fibril-like topology provides a possible explanation for the fast aggregation
      rate of S20G IAPP.

PMID- 23133594
TI  - Fine-scale linkage mapping reveals a small set of candidate genes influencing
      honey bee grooming behavior in response to Varroa mites.
AB  - Populations of honey bees in North America have been experiencing high annual
      colony mortality for 15-20 years. Many apicultural researchers believe that
      introduced parasites called Varroa mites (V. destructor) are the most important
      factor in colony deaths. One important resistance mechanism that limits mite
      population growth in colonies is the ability of some lines of honey bees to groom
      mites from their bodies. To search for genes influencing this trait, we used an
      Illumina Bead Station genotyping array to determine the genotypes of several
      hundred worker bees at over a thousand single-nucleotide polymorphisms in a
      family that was apparently segregating for alleles influencing this behavior.
      Linkage analyses provided a genetic map with 1,313 markers anchored to genome
      sequence. Genotypes were analyzed for association with grooming behavior,
      measured as the time that individual bees took to initiate grooming after mites
      were placed on their thoraces. Quantitative-trait-locus interval mapping
      identified a single chromosomal region that was significant at the chromosome
      wide level (p<0.05) on chromosome 5 with a LOD score of 2.72. The 95% confidence
      interval for quantitative trait locus location contained only 27 genes (honey bee
      official gene annotation set 2) including Atlastin, Ataxin and Neurexin-1
      (AmNrx1), which have potential neurodevelopmental and behavioral effects.
      Atlastin and Ataxin homologs are associated with neurological diseases in humans.
      AmNrx1 codes for a presynaptic protein with many alternatively spliced isoforms.
      Neurexin-1 influences the growth, maintenance and maturation of synapses in the
      brain, as well as the type of receptors most prominent within synapses. Neurexin
      1 has also been associated with autism spectrum disorder and schizophrenia in
      humans, and self-grooming behavior in mice.

PMID- 23133595
TI  - IgG expression in human colorectal cancer and its relationship to cancer cell
      behaviors.
AB  - Increasing evidence indicates that various cancer cell types are capable of
      producing IgG. The exact function of cancer-derived IgG has, however, not been
      elucidated. Here we demonstrated the expression of IgG genes with V(D)J
      recombination in 80 cases of colorectal cancers, 4 colon cancer cell lines and a
      tumor bearing immune deficient mouse model. IgG expression was associated with
      tumor differentiation, pTNM stage, lymph node involvement and inflammatory
      infiltration and positively correlated with the expressions of Cyclin D1, NF
      kappaB and PCNA. Furthermore, we investigated the effect of cancer-derived IgG on
      the malignant behaviors of colorectal cancer cells and showed that blockage of
      IgG resulted in increased apoptosis and negatively affected the potential for
      anchor-independent colony formation and cancer cell invasion. These findings
      suggest that IgG synthesized by colorectal cancer cells is involved in the
      development and growth of colorectal cancer and blockage of IgG may be a
      potential therapy in treating this cancer.

PMID- 23133596
TI  - Metabolite profiling identified methylerythritol cyclodiphosphate efflux as a
      limiting step in microbial isoprenoid production.
AB  - Isoprenoids are natural products that are all derived from isopentenyl
      diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). These precursors are
      synthesized either by the mevalonate (MVA) pathway or the 1-Deoxy-D-Xylulose 5
      Phosphate (DXP) pathway. Metabolic engineering of microbes has enabled
      overproduction of various isoprenoid products from the DXP pathway including
      lycopene, artemisinic acid, taxadiene and levopimaradiene. To date, there is no
      method to accurately measure all the DXP metabolic intermediates simultaneously
      so as to enable the identification of potential flux limiting steps. In this
      study, a solid phase extraction coupled with ultra performance liquid
      chromatography mass spectrometry (SPE UPLC-MS) method was developed. This method
      was used to measure the DXP intermediates in genetically engineered E. coli.
      Unexpectedly, methylerythritol cyclodiphosphate (MEC) was found to efflux when
      certain enzymes of the pathway were over-expressed, demonstrating the existence
      of a novel competing pathway branch in the DXP metabolism. Guided by these
      findings, ispG was overexpressed and was found to effectively reduce the efflux
      of MEC inside the cells, resulting in a significant increase in downstream
      isoprenoid production. This study demonstrated the necessity to quantify
      metabolites enabling the identification of a hitherto unrecognized pathway and
      provided useful insights into rational design in metabolic engineering.

PMID- 23133597
TI  - How the scientific community reacts to newly submitted preprints: article
      downloads, Twitter mentions, and citations.
AB  - We analyze the online response to the preprint publication of a cohort of 4,606
      scientific articles submitted to the preprint database arXiv.org between October
      2010 and May 2011. We study three forms of responses to these preprints:
      downloads on the arXiv.org site, mentions on the social media site Twitter, and
      early citations in the scholarly record. We perform two analyses. First, we
      analyze the delay and time span of article downloads and Twitter mentions
      following submission, to understand the temporal configuration of these reactions
      and whether one precedes or follows the other. Second, we run regression and
      correlation tests to investigate the relationship between Twitter mentions, arXiv
      downloads, and article citations. We find that Twitter mentions and arXiv
      downloads of scholarly articles follow two distinct temporal patterns of
      activity, with Twitter mentions having shorter delays and narrower time spans
      than arXiv downloads. We also find that the volume of Twitter mentions is
      statistically correlated with arXiv downloads and early citations just months
      after the publication of a preprint, with a possible bias that favors highly
      mentioned articles.

PMID- 23133598
TI  - Reg IV is a direct target of intestinal transcriptional factor CDX2 in gastric
      cancer.
AB  - REG4, which encodes Reg IV protein, is a member of the calcium-dependent lectin
      superfamily and potent activator of the epidermal growth factor
      receptor/Akt/activator protein-1 signaling pathway. Several human cancers
      overexpress Reg IV, and Reg IV expression is associated with intestinal phenotype
      differentiation. However, regulation of REG4 transcription remains unclear. In
      the present study, we investigated whether CDX2 regulates Reg IV expression in
      gastric cancer (GC) cells. Expression of Reg IV and CDX2 was analyzed by Western
      blot and quantitative reverse transcription-polymerase chain reaction in 9 GC
      cell lines and 2 colon cancer cell lines. The function of the 5'-flanking region
      of the REG4 gene was characterized by luciferase assay. In 9 GC cell lines,
      endogenous Reg IV and CDX2 expression were well correlated. Using an estrogen
      receptor-regulated form of CDX2, rapid induction of Reg IV expression was
      observed in HT-29 cells. Reporter gene assays revealed an important role in
      transcription for consensus CDX2 DNA binding elements in the 5'-flanking region
      of the REG4 gene. Chromatin immunoprecipitation assays showed that CDX2 binds
      directly to the 5'-flanking region of REG4. These results indicate that CDX2
      protein directly regulates Reg IV expression.

PMID- 23133599
TI  - Asymmetric divergence in structure and function of HCN channel duplicates in
      Ciona intestinalis.
AB  - Hyperpolarization-activated Cyclic Nucleotide (HCN) channels are voltage-gated
      cation channels and are critical for regulation of membrane potential in
      electrically active cells. To understand the evolution of these channels at the
      molecular level, we cloned and examined two of three HCN homologs of the
      urochordate Ciona intestinalis (ciHCNa and ciHCNb). ciHCNa is like mammalian HCNs
      in that it possesses similar electrical function and undergoes N-glycosylation of
      a sequon near the pore. ciHCNb lacks the pore-associated N-glycosylation sequon
      and is predictably not N-glycosylated, and it also has an unusual gating
      phenotype in which the channel's voltage-sensitive gate appears to close
      incompletely. Together with previous findings, the data support an evolutionary
      trajectory in which an HCN ancestor underwent lineage-specific duplication in
      Ciona, to yield one HCN with most features that are conserved with the mammalian
      HCNs and another HCN that has been uniquely altered.

PMID- 23133600
TI  - Assessment of host-associated genetic differentiation among phenotypically
      divergent populations of a coral-eating gastropod across the Caribbean.
AB  - Host-associated adaptation is emerging as a potential driver of population
      differentiation and speciation for marine organisms with major implications for
      ecosystem structure and function. Coralliophila abbreviata are corallivorous
      gastropods that live and feed on most of the reef-building corals in the tropical
      western Atlantic and Caribbean. Populations of C. abbreviata associated with the
      threatened acroporid corals, Acropora palmata and A. cervicornis, display
      different behavioral, morphological, demographic, and life-history
      characteristics than those that inhabit other coral host taxa, indicating that
      host-specific selective forces may be acting on C. abbreviata. Here, we used
      newly developed polymorphic microsatellite loci and mitochondrial cytochrome b
      sequence data to assess the population genetic structure, connectivity, and
      demographic history of C. abbreviata populations from three coral host taxa (A.
      palmata, Montastraea spp., Mycetophyllia spp.) and six geographic locations
      across the Caribbean. Analysis of molecular variance provided some evidence of
      weak and possibly geographically variable host-associated differentiation but no
      evidence of differentiation among sampling locations or major oceanographic
      regions, suggesting high gene flow across the Caribbean. Phylogenetic network and
      bayesian clustering analyses supported a hypothesis of a single panmictic
      population as individuals failed to cluster by host or sampling location.
      Demographic analyses consistently supported a scenario of population expansion
      during the Pleistocene, a time of major carbonate reef development in the region.
      Although further study is needed to fully elucidate the interactive effects of
      host-associated selection and high gene flow in this system, our results have
      implications for local and regional community interactions and impact of
      predation on declining coral populations.

PMID- 23133601
TI  - Clinical and demographic characteristics of patients with urinary tract hydatid
      disease.
AB  - BACKGROUND: Human cystic echinococcosis (CE) is caused by flatworm larvae of
      Echinococcus granulosus and is endemic in many parts of the world. In humans, CE
      cysts primarily affect the liver and pulmonary system, but can also affect the
      renal system. However, the clinical manifestations of renal CE can be subtle, so
      healthcare professionals often overlook renal CE in differential diagnosis. In
      this study, we examined the clinical and demographic characteristics of patients
      with urinary tract CE and analyzed the diagnosis and treatment procedures for
      this disease. METHODS: The records of 19 consecutive renal CE patients who were
      admitted to the First Affiliated Hospital of Xinjiang Medical University from
      January 1983 to April 2011 were retrospectively reviewed. In all cases, CE of the
      urinary tract was confirmed by pathological examination and visual inspection
      during surgery. RESULTS: Fifteen patients were males and 4 were females. The most
      common symptoms were non-specific lower back pain and percussion tenderness on
      the kidney region. All patients were followed up for 9-180 months after surgery.
      None of the patients experienced a recurrence of renal CE, but 4 patients
      experienced non-renal recurrence of hydatid disease. CONCLUSIONS: Hydatid cysts
      from E. granulosus are structurally similar in the liver and urinary tract. Thus,
      the treatment regimen for liver CE developed by the World Health
      Organization/Informal Working Group on Echinococcosis (WHO/IWGE) could also be
      used for urinary tract CE. In our patients, the use of ultrasound, computed
      tomography, serology, and clinical characteristics provided a diagnostic accuracy
      of 66.7% to 92.3%.

PMID- 23133602
TI  - Pharmacogenetics of efficacy and safety of HCV treatment in HCV-HIV coinfected
      patients: significant associations with IL28B and SOCS3 gene variants.
AB  - BACKGROUND AND AIMS: This was a safety and efficacy pharmacogenetic study of a
      previously performed randomized trial which compared the effectiveness of
      treatment of hepatitis C virus infection with pegylated interferon alpha
      (pegIFNalpha) 2a vs. 2b, both with ribavirin, for 48 weeks, in HCV-HIV coinfected
      patients. METHODS: The study groups were made of 99 patients (efficacy
      pharmacogenetic substudy) and of 114 patients (safety pharmacogenetic substudy).
      Polymorphisms in the following candidate genes IL28B, IL6, IL10, TNFalpha,
      IFNgamma, CCL5, MxA, OAS1, SOCS3, CTLA4 and ITPA were assessed. Genotyping was
      carried out using Sequenom iPLEX-Gold, a single-base extension polymerase chain
      reaction. Efficacy end-points assessed were: rapid, early and sustained
      virological response (RVR, EVR and SVR, respectively). Safety end-points assessed
      were: anemia, neutropenia, thrombocytopenia, flu-like syndrome, gastrointestinal
      disturbances and depression. Chi square test, Student's T test, Mann-Whitney U
      test and logistic regression were used for statistic analyses. RESULTS: As
      efficacy is concerned, IL28B and CTLA4 gene polymorphisms were associated with
      RVR (p<0.05 for both comparisons). Nevertheless, only polymorphism in the IL28B
      gene was associated with SVR (p = 0.004). In the multivariate analysis, the only
      gene independently associated with SVR was IL28B (OR 2.61, 95%CI 1.2-5.6, p =
      0.01). With respect to safety, there were no significant associations between flu
      like syndrome or depression and the genetic variants studied. Gastrointestinal
      disturbances were associated with ITPA gene polymorphism (p = 0.04). Anemia was
      associated with OAS1 and CTLA4 gene polymorphisms (p = 0.049 and p = 0.045,
      respectively), neutropenia and thromobocytopenia were associated with SOCS3 gene
      polymorphism (p = 0.02 and p = 0.002, respectively). In the multivariate
      analysis, the associations of the SOCS3 gene polymorphism with neutropenia (OR
      0.26, 95%CI 0.09-0.75, p = 0.01) and thrombocytopenia (OR 0.07, 95%CI 0.008-0.57,
      p = 0.01) remained significant. CONCLUSIONS: In HCV-HIV coinfected patients
      treated with PegIFNalpha and ribavirin, SVR is associated with IL28B rs8099917
      polymorphism. HCV treatment-induced neutropenia and thrombocytopenia are
      associated with SOCS3 rs4969170 polymorphism.

PMID- 23133603
TI  - Genome-wide comparative analysis of annexin superfamily in plants.
AB  - Most annexins are calcium-dependent, phospholipid-binding proteins with suggested
      functions in response to environmental stresses and signaling during plant growth
      and development. They have previously been identified and characterized in
      Arabidopsis and rice, and constitute a multigene family in plants. In this study,
      we performed a comparative analysis of annexin gene families in the sequenced
      genomes of Viridiplantae ranging from unicellular green algae to multicellular
      plants, and identified 149 genes. Phylogenetic studies of these deduced annexins
      classified them into nine different arbitrary groups. The occurrence and
      distribution of bona fide type II calcium binding sites within the four annexin
      domains were found to be different in each of these groups. Analysis of
      chromosomal distribution of annexin genes in rice, Arabidopsis and poplar
      revealed their localization on various chromosomes with some members also found
      on duplicated chromosomal segments leading to gene family expansion. Analysis of
      gene structure suggests sequential or differential loss of introns during the
      evolution of land plant annexin genes. Intron positions and phases are well
      conserved in annexin genes from representative genomes ranging from
      Physcomitrella to higher plants. The occurrence of alternative motifs such as
      K/R/HGD was found to be overlapping or at the mutated regions of the type II
      calcium binding sites indicating potential functional divergence in certain plant
      annexins. This study provides a basis for further functional analysis and
      characterization of annexin multigene families in the plant lineage.

PMID- 23133604
TI  - The prognosis of allocentric and egocentric neglect: evidence from clinical
      scans.
AB  - We contrasted the neuroanatomical substrates of sub-acute and chronic
      visuospatial deficits associated with different aspects of unilateral neglect
      using computed tomography scans acquired as part of routine clinical diagnosis.
      Voxel-wise statistical analyses were conducted on a group of 160 stroke patients
      scanned at a sub-acute stage. Lesion-deficit relationships were assessed across
      the whole brain, separately for grey and white matter. We assessed lesions that
      were associated with behavioural performance (i) at a sub-acute stage (within 3
      months of the stroke) and (ii) at a chronic stage (after 9 months post stroke).
      Allocentric and egocentric neglect symptoms at the sub-acute stage were
      associated with lesions to dissociated regions within the frontal lobe, amongst
      other regions. However the frontal lesions were not associated with neglect at
      the chronic stage. On the other hand, lesions in the angular gyrus were
      associated with persistent allocentric neglect. In contrast, lesions within the
      superior temporal gyrus extending into the supramarginal gyrus, as well as
      lesions within the basal ganglia and insula, were associated with persistent
      egocentric neglect. Damage within the temporo-parietal junction was associated
      with both types of neglect at the sub-acute stage and 9 months later.
      Furthermore, white matter disconnections resulting from damage along the superior
      longitudinal fasciculus were associated with both types of neglect and critically
      related to both sub-acute and chronic deficits. Finally, there was a significant
      difference in the lesion volume between patients who recovered from neglect and
      patients with chronic deficits. The findings presented provide evidence that (i)
      the lesion location and lesion size can be used to successfully predict the
      outcome of neglect based on clinical CT scans, (ii) lesion location alone can
      serve as a critical predictor for persistent neglect symptoms, (iii) wide spread
      lesions are associated with neglect symptoms at the sub-acute stage but only some
      of these are critical for predicting whether neglect will become a chronic
      disorder and (iv) the severity of behavioural symptoms can be a useful predictor
      of recovery in the absence of neuroimaging findings on clinical scans. We discuss
      the implications for understanding the symptoms of the neglect syndrome, the
      recovery of function and the use of clinical scans to predict outcome.

PMID- 23133605
TI  - N-type thermoelectric performance of functionalized carbon nanotube-filled
      polymer composites.
AB  - Carbon nanotubes (CNTs) were functionalized with polyethyleneimine (PEI) and made
      into composites with polyvinyl acetate (PVAc). CNTs were dispersed with different
      amounts of sodium dodecylbenzenesulfonate (SDBS) prior to the PEI
      functionalization. The resulting samples exhibit air-stable n-type
      characteristics with electrical conductivities as great as 1500 S/m and
      thermopowers as large as -100 uV/K. Electrical conductivity and thermopower were
      strongly affected by CNT dispersion, improving the properties with better
      dispersion with high concentrations of SDBS. This improvement is believed to be
      due to the increase in the number of tubes that are evenly coated with PEI in a
      better-dispersed sample. Increasing the amount of PEI relative to the other
      constituents positively affects thermopower but not conductivity. Air exposure
      reduces both thermopower and conductivity presumably due to oxygen doping (which
      makes CNTs p-type), but stable values were reached within seven days following
      sample fabrication.

PMID- 23133606
TI  - Genetic and environmental influences on the relationship between flow proneness,
      locus of control and behavioral inhibition.
AB  - Flow is a psychological state of high but subjectively effortless attention that
      typically occurs during active performance of challenging tasks and is
      accompanied by a sense of automaticity, high control, low self-awareness, and
      enjoyment. Flow proneness is associated with traits and behaviors related to low
      neuroticism such as emotional stability, conscientiousness, active coping, self
      esteem and life satisfaction. Little is known about the genetic architecture of
      flow proneness, behavioral inhibition and locus of control--traits also
      associated with neuroticism--and their interrelation. Here, we hypothesized that
      individuals low in behavioral inhibition and with an internal locus of control
      would be more likely to experience flow and explored the genetic and
      environmental architecture of the relationship between the three variables.
      Behavioral inhibition and locus of control was measured in a large population
      sample of 3,375 full twin pairs and 4,527 single twins, about 26% of whom also
      scored the flow proneness questionnaire. Findings revealed significant but
      relatively low correlations between the three traits and moderate heritability
      estimates of .41, .45, and .30 for flow proneness, behavioral inhibition, and
      locus of control, respectively, with some indication of non-additive genetic
      influences. For behavioral inhibition we found significant sex differences in
      heritability, with females showing a higher estimate including significant non
      additive genetic influences, while in males the entire heritability was due to
      additive genetic variance. We also found a mainly genetically mediated
      relationship between the three traits, suggesting that individuals who are
      genetically predisposed to experience flow, show less behavioral inhibition (less
      anxious) and feel that they are in control of their own destiny (internal locus
      of control). We discuss that some of the genes underlying this relationship may
      include those influencing the function of dopaminergic neural systems.

PMID- 23133607
TI  - Associations between gene expression variations and ovarian cancer risk alleles
      identified from genome wide association studies.
AB  - Functional genetic variations play important roles in shaping phenotypic
      differences among individuals through affecting gene expression, and thus, very
      likely to influence disease susceptibility, such as cancer susceptibility. One
      critical question in this era of post-genome wide association studies (GWAS) is
      how to assess the functional significance of the genetic variations identified
      from GWAS. In the current study, with lymphoblastoid cell lines (LCLs) from 74
      non-related women with familial ovarian cancer and 47 unrelated controls matched
      on gender and race, we explored the associations between seven ovarian cancer
      risk variants identified from GWAS (rs3814113 on 9p22.2, rs2072590 on 2q31,
      rs2665390 on 3q25, rs10088218, rs1516982, rs10098821 on 8q24.21, and rs2363956 on
      19p13) and whole genome mRNA expression profiles. We observed 95 significant
      trans-associations at a permutation level of 0.001. Compared to the other risk
      variants, rs10088218, rs1516982, and rs10098821 on 8q24.21 had the greatest
      number of significant associations (25, 16, and 38, respectively). Two possible
      cis-associations were observed between rs10098821 and c-Myc, and rs2072590 and
      HS.565379 (Permutated P = 0.0198 and 0.0399, respectively). Pathway enrichment
      analysis showed that several key biological pathways, such as cell cycle (P =
      2.59*10(-06)), etc, were significantly overrepresented. Further characterization
      of significant associations between mRNAs and risk alleles might facilitate
      understanding the functions of GWAS discovered risk alleles in the genetic
      etiology of ovarian cancer.

PMID- 23133608
TI  - Peroxisomal localization and circadian regulation of ubiquitin-specific protease
      2.
AB  - Temporal regulation of nutrient and energy metabolism is emerging as an important
      aspect of metabolic homeostasis. The regulatory network that integrates the
      timing cues and nutritional signals to drive diurnal metabolic rhythms remains
      poorly defined. The 45-kDa isoform of ubiquitin-specific protease 2 (USP2-45) is
      a deubiquitinase that regulates hepatic gluconeogenesis and glucose metabolism.
      In this study, we found that USP2-45 is localized to peroxisomes in hepatocytes
      through a canonical peroxisome-targeting motif at its C-terminus. Clustering
      analysis indicates that the expression of a subset of peroxisomal genes exhibits
      robust diurnal rhythm in the liver. Despite this, nuclear hormone receptor
      PPARalpha, a known regulator of peroxisome gene expression, does not induce USP2
      45 in hepatocytes and is dispensible for its expression during starvation. In
      contrast, a functional liver clock is required for the proper nutritional and
      circadian regulation of USP2-45 expression. At the molecular level,
      transcriptional coactivators PGC-1alpha and PGC-1beta and repressor E4BP4 exert
      opposing effects on USP2-45 promoter activity. These studies provide insights
      into the subcellular localization and transcriptional regulation of a clock
      controlled deubiquitinase that regulates glucose metabolism.

PMID- 23133610
TI  - 3-Pyridyl substituted aliphatic cycles as CYP11B2 inhibitors: aromaticity
      abolishment of the core significantly increased selectivity over CYP1A2.
AB  - Aldosterone synthase (CYP11B2) is a promising therapeutic target for the
      treatment of cardiovascular diseases related to abnormally high aldosterone
      levels. On the basis of our previously identified lead compounds I-III, a series
      of 3-pyridinyl substituted aliphatic cycles were designed, synthesized and tested
      as CYP11B2 inhibitors. Aromaticity abolishment of the core was successfully
      applied to overcome the undesired CYP1A2 inhibition. This study resulted in a
      series of potent and selective CYP11B2 inhibitors, with compound 12 (IC(50) = 21
      nM, SF = 50) as the most promising one, which shows no inhibition toward CYP1A2
      at 2 uM. The design conception demonstrated in this study can be helpful in the
      optimization of CYP inhibitor drugs regarding CYP1A2 selectivity.

PMID- 23133609
TI  - Serum BDNF concentrations show strong seasonal variation and correlations with
      the amount of ambient sunlight.
AB  - Earlier findings show seasonality in processes and behaviors such as brain
      plasticity and depression that in part are regulated by Brain-Derived
      Neurotrophic Factor (BDNF). Based on this we investigated seasonal variation in
      serum BDNF concentrations in 2,851 persons who took part in the Netherlands Study
      of Depression and Anxiety (NESDA). Analyses by month of sampling (monthly n's
      >196) showed pronounced seasonal variation in serum BDNF concentrations (P<.0001)
      with increasing concentrations in the spring-summer period (standardized
      regression weight (beta) = 0.19, P<.0001) and decreasing concentrations in the
      autumn-winter period (beta = -0.17, P<.0001). Effect sizes [Cohen's d] ranged
      from 0.27 to 0.66 for monthly significant differences. We found similar seasonal
      variation for both sexes and for persons with a DSM-IV depression diagnosis and
      healthy control subjects. In explorative analyses we found that the number of
      sunshine hours (a major trigger to entrain seasonality) in the week of blood
      withdrawal and the 10 weeks prior to this event positively correlated with serum
      BDNF concentrations (Pearson's correlation coefficients ranged: 0.05-0.18) and
      this could partly explain the observed monthly variation. These results provide
      strong evidence that serum BDNF concentrations systematically vary over the year.
      This finding is important for our understanding of those factors that regulate
      BDNF expression and may provide novel avenues to understand seasonal dependent
      changes in behavior and illness such as depression. Finally, the findings
      reported here should be taken into account when designing and interpreting
      studies on BDNF.

PMID- 23133611
TI  - Artepillin C, a major ingredient of Brazilian propolis, induces a pungent taste
      by activating TRPA1 channels.
AB  - Brazilian green propolis is a popular health supplement because of its various
      biological properties. The ethanol extract of Brazilian green propolis (EEBP) is
      characteristic for its herb-like smell and unique pungent taste. However, the
      ingredients responsible for its pungency have not yet been identified. This study
      provides the first evidence that artepillin C is the main pungent ingredient in
      EEBP and that it potently activates human transient receptor potential ankyrin 1
      (TRPA1) channels. EEBP was fractionated using column chromatography with a step
      gradient elution of an ethanol-water solution, and the fractions having the
      pungent taste were determined by sensory tests. HPLC analysis revealed that the
      pungent fraction was composed primarily of artepillin C, a prenylated derivative
      of cinnamic acid. Artepillin C was also identified as the pungent compound of
      EEBP by organoleptic examiners. Furthermore, the effects of artepillin C and
      other cinnamic acids found in EEBP on TRPA1 channels were examined by calcium
      imaging and plate reader-based assays in human TRPA1-expressing cells to
      investigate the molecular mechanisms underlying their pungent tastes. Artepillin
      C and baccharin activated the TRPA1 channel strongly, whereas drupanin caused a
      slight activation and p-coumaric acid showed no activation. Because the EC(50)
      values of artepillin C, baccharin, and allyl isothiocyanate were 1.8 uM, 15.5 uM,
      and 6.2 uM, respectively, artepillin C was more potent than the typical TRPA1
      agonist allyl isothiocyanate. These findings strongly indicate that artepillin C
      is the main pungent ingredient in EEBP and stimulates a pungent taste by
      activating TRPA1 channels.

PMID- 23133612
TI  - Predicting daily physical activity in patients with chronic obstructive pulmonary
      disease.
AB  - BACKGROUND: Objectively measuring daily physical activity (PA) using an
      accelerometer is a relatively expensive and time-consuming undertaking. In
      routine clinical practice it would be useful to estimate PA in patients with
      chronic obstructive pulmonary disease (COPD) with more simple methods.
      OBJECTIVES: To evaluate whether PA can be estimated by simple tests commonly used
      in clinical practice in patients with COPD. METHODS: The average number of steps
      per day was measured for 7 days with a SenseWear ProTM accelerometer and used as
      gold standard for PA. A physical activity level (PAL) of <1.4 was considered very
      inactive. Univariate and multivariate analyses were used to examine the
      relationship between the 6-minute walking distance (6MWD), the number of stands
      in the Sit-to-Stand Test (STST), hand-grip strength and the total energy
      expenditure as assessed by the Zutphen Physical Activity Questionnaire
      (TEE(ZPAQ)). ROC curve analysis was used to identify patients with an extremely
      inactive lifestyle (PAL<1.4). RESULTS: In 70 patients with COPD (21 females) with
      a mean [SD] FEV(1) of 43.0 [22.0] %predicted, PA was found to be significantly
      and independently associated with the 6MWD (r = 0.69, 95% CI 0.54 to 0.80,
      p<0.001), STST (r = 0.51, 95% CI 0.31 to 0.66, p = 0.001) and TEEZPAQ (r = 0.50,
      95% CI 0.30 to 0.66, p<0.001) but not with hand-grip strength. However, ROC curve
      analysis demonstrated that these tests cannot be used to reliably identify
      patients with an extremely inactive lifestyle. CONCLUSIONS: In patients with COPD
      simple tests such as the 6-Minute Walk Test, the Sit-to-Stand Test and the
      Zutphen Physical Activity Questionnaire cannot be used to reliably predict
      physical inactivity.

PMID- 23133613
TI  - The pentameric channel of COMPcc in complex with different fatty acids.
AB  - BACKGROUND: COMPcc forms a pentameric left-handed coiled coil that is known to
      bind hydrophilic signaling molecules such as vitamin D(3), and vitamin A.
      PRINCIPAL FINDINGS: In an integrated approach we reveal the unique binding
      properties of COMPcc for saturated and unsaturated fatty acids. Our observations
      suggest that residues Met33 (gating pore), Thr40/Asn41 (water chamber) and Gln54
      (electrostatic trap) are key elements for the binding of fatty acids by COMPcc.
      In addition, this work characterizes the binding of various fatty acids to COMPcc
      using fluorescence spectroscopy. Our findings reveal a binding trend within the
      hydrophobic channel of COMPcc, namely, that is driven by length of the methylene
      tail and incorporation of unsaturation. CONCLUSION/SIGNIFICANCE: The unique
      binding properties imply that COMPcc may be involved in signalling functions in
      which hydrophilic ligands are involved. The pentameric channel is a unique
      carrier for lipophilic compounds. This opens the exciting possibility that COMPcc
      could be developed as a targeted drug delivery system.

PMID- 23133614
TI  - Silencing prion protein in MDA-MB-435 breast cancer cells leads to pleiotropic
      cellular responses to cytotoxic stimuli.
AB  - Prion protein (PrP) is well studied for its pathogenic role in prion disease, but
      its potential contribution to other pathological processes is less understood.
      PrP is expressed in a variety of cancers and at least in pancreatic and breast
      cancers, its expression appears to be associated with poor prognosis. To
      understand the role of PrP in breast cancer cells, we knocked down PrP expression
      in MDA-MB-435 breast cancer cells with small interfering RNA and subjected these
      cells to a series of analyses. We found that PrP knockdown in these cells does
      not affect cell proliferation or colony formation, but significantly influences
      the cellular response to cytotoxic stimuli. Compared to control cells, PrP
      knockdown cells exhibited an increased susceptibility to serum deprivation
      induced apoptosis, no change to staurosporine- or paclitaxel-induced cell deaths,
      and a reduced susceptibility to chemotherapy drug doxorubicin-induced cell death.
      To understand the mechanism of unexpected role of PrP in exacerbating doxorubicin
      induced cytotoxicity, we analyzed cell death related Bcl-2 family proteins. We
      found that PrP knockdown alters the expression of several Bcl-2 family proteins,
      correlating with increased resistance to doxorubicin-induced cytotoxicity.
      Moreover, the enhanced doxorubicin resistance is independent of DNA damage
      related p53 pathway, but at least partially through the ERK1/2 pathway. Together,
      our study revealed that silencing PrP in MDA-MB-435 breast cancer cells results
      in very different responses to various cytotoxic stimuli and ERK1/2 signaling
      pathway is involved in PrP silencing caused resistance to doxorubicin.

PMID- 23133615
TI  - Regional homogeneity within the default mode network in bipolar depression: a
      resting-state functional magnetic resonance imaging study.
AB  - AIM: We sought to use a regional homogeneity (ReHo) approach as an index in
      resting-state functional magnetic resonance imaging (fMRI) to investigate the
      features of spontaneous brain activity within the default mode network (DMN) in
      patients suffering from bipolar depression (BD). METHODS: Twenty-six patients
      with BD and 26 gender-, age-, and education-matched healthy subjects participated
      in the resting-state fMRI scans. We compared the differences in ReHo between the
      two groups within the DMN and investigated the relationships between sex, age,
      years of education, disease duration, the Hamilton Rating Scale for Depression
      (HAMD) total score, and ReHo in regions with significant group differences.
      RESULTS: Our results revealed that bipolar depressed patients had increased ReHo
      in the left medial frontal gyrus and left inferior parietal lobe compared to
      healthy controls. No correlations were found between regional ReHo values and
      sex, age, and clinical features within the BD group. CONCLUSIONS: Our findings
      indicate that abnormal brain activity is mainly distributed within prefrontal
      limbic circuits, which are believed to be involved in the pathophysiological
      mechanisms underlying bipolar depression.

PMID- 23133616
TI  - Pharmacokinetic properties of 2nd-generation fibroblast growth factor-1 mutants
      for therapeutic application.
AB  - Fibroblast growth factor-1 (FGF-1) is an angiogenic factor with therapeutic
      potential for the treatment of ischemic disease. FGF-1 has low intrinsic
      thermostability and is characteristically formulated with heparin as a
      stabilizing agent. Heparin, however, adds a number of undesirable properties that
      negatively impact safety and cost. Mutations that increase the thermostability of
      FGF-1 may obviate the need for heparin in formulation and may prove to be useful
      "2nd-generation" forms for therapeutic use. We report a pharmacokinetic (PK)
      study in rabbits of human FGF-1 in the presence and absence of heparin, as well
      as three mutant forms having differential effects upon thermostability, buried
      reactive thiols, and heparin affinity. The results support the hypothesis that
      heparan sulfate proteoglycan (HSPG) in the vasculature of liver, kidney and
      spleen serves as the principle peripheral compartment in the distribution
      kinetics. The addition of heparin to FGF-1 is shown to increase endocrine-like
      properties of distribution. Mutant forms of FGF-1 that enhance thermostability or
      eliminate buried reactive thiols demonstrate a shorter distribution half-life, a
      longer elimination half-life, and a longer mean residence time (MRT) in
      comparison to wild-type FGF-1. The results show how such mutations can produce
      useful 2nd-generation forms with tailored PK profiles for specific therapeutic
      application.

PMID- 23133617
TI  - High-fat diet induces periodontitis in mice through lipopolysaccharides (LPS)
      receptor signaling: protective action of estrogens.
AB  - BACKGROUND: A fat-enriched diet favors the development of gram negative bacteria
      in the intestine which is linked to the occurrence of type 2 diabetes (T2D).
      Interestingly, some pathogenic gram negative bacteria are commonly associated
      with the development of periodontitis which, like T2D, is characterized by a
      chronic low-grade inflammation. Moreover, estrogens have been shown to regulate
      glucose homeostasis via an LPS receptor dependent immune-modulation. In this
      study, we evaluated whether diet-induced metabolic disease would favor the
      development of periodontitis in mice. In addition, the regulatory role of
      estrogens in this process was assessed. METHODS: Four-week-old C57BL6/J WT and
      CD14 (part of the TLR-4 machinery for LPS-recognition) knock-out female mice were
      ovariectomised and subcutaneously implanted with pellets releasing either placebo
      or 17beta-estradiol (E2). Mice were then fed with either a normal chow or a high
      fat diet for four weeks. The development of diabetes was monitored by an
      intraperitoneal glucose-tolerance test and plasma insulin concentration while
      periodontitis was assessed by identification of pathogens, quantification of
      periodontal soft tissue inflammation and alveolar bone loss. RESULTS: The fat
      enriched diet increased the prevalence of periodontal pathogenic microbiota like
      Fusobacterium nucleatum and Prevotella intermedia, gingival inflammation and
      alveolar bone loss. E2 treatment prevented this effect and CD14 knock-out mice
      resisted high-fat diet-induced periodontal defects. CONCLUSIONS/SIGNIFICANCE: Our
      data show that mice fed with a diabetogenic diet developed defects and microflora
      of tooth supporting-tissues typically associated with periodontitis. Moreover,
      our results suggest a causal link between the activation of the LPS pathway on
      innate immunity by periodontal microbiota and HFD-induced periodontitis, a
      pathophysiological mechanism that could be targeted by estrogens.

PMID- 23133618
TI  - Genomic comparison of Escherichia coli O104:H4 isolates from 2009 and 2011
      reveals plasmid, and prophage heterogeneity, including shiga toxin encoding phage
      stx2.
AB  - In May of 2011, an enteroaggregative Escherichia coli O104:H4 strain that had
      acquired a Shiga toxin 2-converting phage caused a large outbreak of bloody
      diarrhea in Europe which was notable for its high prevalence of hemolytic uremic
      syndrome cases. Several studies have described the genomic inventory and
      phylogenies of strains associated with the outbreak and a collection of
      historical E. coli O104:H4 isolates using draft genome assemblies. We present the
      complete, closed genome sequences of an isolate from the 2011 outbreak (2011C
      3493) and two isolates from cases of bloody diarrhea that occurred in the
      Republic of Georgia in 2009 (2009EL-2050 and 2009EL-2071). Comparative genome
      analysis indicates that, while the Georgian strains are the nearest neighbors to
      the 2011 outbreak isolates sequenced to date, structural and nucleotide-level
      differences are evident in the Stx2 phage genomes, the mer/tet antibiotic
      resistance island, and in the prophage and plasmid profiles of the strains,
      including a previously undescribed plasmid with homology to the pMT virulence
      plasmid of Yersinia pestis. In addition, multiphenotype analysis showed that
      2009EL-2071 possessed higher resistance to polymyxin and membrane-disrupting
      agents. Finally, we show evidence by electron microscopy of the presence of a
      common phage morphotype among the European and Georgian strains and a second
      phage morphotype among the Georgian strains. The presence of at least two stx2
      phage genotypes in host genetic backgrounds that may derive from a recent common
      ancestor of the 2011 outbreak isolates indicates that the emergence of stx2 phage
      containing E. coli O104:H4 strains probably occurred more than once, or that the
      current outbreak isolates may be the result of a recent transfer of a new stx2
      phage element into a pre-existing stx2-positive genetic background.

PMID- 23133619
TI  - The Multidimensional Assessment of Interoceptive Awareness (MAIA).
AB  - This paper describes the development of a multidimensional self-report measure of
      interoceptive body awareness. The systematic mixed-methods process involved
      reviewing the current literature, specifying a multidimensional conceptual
      framework, evaluating prior instruments, developing items, and analyzing focus
      group responses to scale items by instructors and patients of body awareness
      enhancing therapies. Following refinement by cognitive testing, items were field
      tested in students and instructors of mind-body approaches. Final item selection
      was achieved by submitting the field test data to an iterative process using
      multiple validation methods, including exploratory cluster and confirmatory
      factor analyses, comparison between known groups, and correlations with
      established measures of related constructs. The resulting 32-item
      multidimensional instrument assesses eight concepts. The psychometric properties
      of these final scales suggest that the Multidimensional Assessment of
      Interoceptive Awareness (MAIA) may serve as a starting point for research and
      further collaborative refinement.

PMID- 23133620
TI  - In vivo anti-HIV activity of the heparin-activated serine protease inhibitor
      antithrombin III encapsulated in lymph-targeting immunoliposomes.
AB  - Endogenous serine protease inhibitors (serpins) are anti-inflammatory mediators
      with multiple biologic functions. Several serpins have been reported to modulate
      HIV pathogenesis, or exhibit potent anti-HIV activity in vitro, but the efficacy
      of serpins as therapeutic agents for HIV in vivo has not yet been demonstrated.
      In the present study, we show that heparin-activated antithrombin III (hep
      ATIII), a member of the serpin family, significantly inhibits lentiviral
      replication in a non-human primate model. We further demonstrate greater than one
      log(10) reduction in plasma viremia in the nonhuman primate system by loading of
      hep-ATIII into anti-HLA-DR immunoliposomes, which target tissue reservoirs of
      viral replication. We also demonstrate the utility of hep-ATIIII as a potential
      salvage agent for HIV strains resistant to standard anti-retroviral treatment.
      Finally, we applied gene-expression arrays to analyze hep-ATIII-induced host cell
      interactomes and found that downstream of hep-ATIII, two independent gene
      networks were modulated by host factors prostaglandin synthetase-2, ERK1/2 and
      NFkappaB. Ultimately, understanding how serpins, such as hep-ATIII, regulate host
      responses during HIV infection may reveal new avenues for therapeutic
      intervention.

PMID- 23133621
TI  - The Arabidopsis thaliana immunophilin ROF1 directly interacts with PI(3)P and
      PI(3,5)P2 and affects germination under osmotic stress.
AB  - A direct interaction of the Arabidopsis thaliana immunophilin ROF1 with
      phosphatidylinositol-3-phosphate and phosphatidylinositol-3,5-bisphosphate was
      identified using a phosphatidylinositol-phosphate affinity chromatography of cell
      suspension extracts, combined with a mass spectrometry (nano LC ESI-MS/MS)
      analysis. The first FK506 binding domain was shown sufficient to bind to both
      phosphatidylinositol-phosphate stereoisomers. GFP-tagged ROF1 under the control
      of a 35S promoter was localised in the cytoplasm and the cell periphery of
      Nicotiana tabacum leaf explants. Immunofluorescence microscopy of Arabidopsis
      thaliana root tips verified its cytoplasmic localization and membrane association
      and showed ROF1 localization in the elongation zone which was expanded to the
      meristematic zone in plants grown on high salt media. Endogenous ROF1 was shown
      to accumulate in response to high salt treatment in Arabidopsis thaliana young
      leaves as well as in seedlings germinated on high salt media (0.15 and 0.2 M
      NaCl) at both an mRNA and protein level. Plants over-expressing ROF1, (WSROF1OE),
      exhibited enhanced germination under salinity stress which was significantly
      reduced in the rof1(-) knock out mutants and abolished in the double mutants of
      ROF1 and of its interacting homologue ROF2 (WSrof1(-)/2(-)). Our results show
      that ROF1 plays an important role in the osmotic/salt stress responses of
      germinating Arabidopsis thaliana seedlings and suggest its involvement in
      salinity stress responses through a phosphatidylinositol-phosphate related
      protein quality control pathway.

PMID- 23133622
TI  - An intrinsically disordered region of the acetyltransferase p300 with similarity
      to prion-like domains plays a role in aggregation.
AB  - Several human diseases including neurodegenerative disorders and cancer are
      associated with abnormal accumulation and aggregation of misfolded proteins.
      Proteins with high tendency to aggregate include the p53 gene product, TAU and
      alpha synuclein. The potential toxicity of aberrantly folded proteins is limited
      via their transport into intracellular sub-compartments, the aggresomes, where
      misfolded proteins are stored or cleared via autophagy. We have identified a
      region of the acetyltransferase p300 that is highly disordered and displays
      similarities with prion-like domains. We show that this region is encoded as an
      alternative spliced variant independently of the acetyltransferase domain, and
      provides an interaction interface for various misfolded proteins, promoting their
      aggregation. p300 enhances aggregation of TAU and of p53 and is a component of
      cellular aggregates in both tissue culture cells and in alpha-synuclein positive
      Lewy bodies of patients affected by Parkinson disease. Down-regulation of p300
      impairs aggresome formation and enhances cytotoxicity induced by misfolded
      protein stress. These data unravel a novel activity of p300, offer new insights
      into the function of disordered domains and implicate p300 in pathological
      aggregation that occurs in neurodegeneration and cancer.

PMID- 23133623
TI  - Down-regulation of hydrogen sulfide biosynthesis accompanies murine interstitial
      cells of Cajal dysfunction in partial ileal obstruction.
AB  - PURPOSE: To investigate the role of endogenous hydrogen sulfide (H(2)S) in
      partial obstruction-induced dysfunction of the interstitial cells of Cajal (ICC)
      in mice ileum. MATERIALS AND METHODS: Partial intestinal obstruction was induced
      surgically in male imprinting control region (ICR) mice. ICC networks were
      studied by Immunohistochemistry. Electrical activity was recorded by
      intracellular recording techniques. The expression of ICC phenotype marker c-kit
      receptor tyrosine kinase (c-kit), membrane binding stem cell factor (mSCF), the
      endogenous H(2)S biosynthesis enzymes cystathionine-beta-synthase (CBS) and
      cystathionine-gamma-lyase (CSE) was studied by Western blotting. The expression
      of tumor necrosis factor-alpha (TNF-alpha) mRNA was observed by using real-time
      polymerase chain reaction. RESULTS: Partial intestinal obstruction resulted in
      ICC networks were disrupted above obstruction 14 days after the operation. The
      slow waves of intestinal smooth muscles in the dilated region were significantly
      suppressed and their amplitude and frequency were reduced, whilst the resting
      membrane potentials were depolarized. The expression of c-kit and mSCF was
      significantly decreased, also suggesting the disruption of the ICC network. The
      expression of TNF-alpha was significantly increased in the tunica muscularis of
      the obstructed intestine. Treatment of cultured intestinal smooth muscle cells
      with TNF-alpha caused dramatic down regulation of mSCF. The expression of CBS and
      CSE was significantly decreased in the tunica muscularis of the obstructed
      intestine. Intraperitoneal injection (i.p) of DL-propargylglycine, an
      irreversible inhibitor of CSE, and aminooxyacetic acid, an inhibitor of CBS,
      elevated the expression of TNF-alpha mRNA in the tunica muscularis of the ileum.
      Obstruction-induced over expression of TNF-alpha was significantly improved by
      supplementation of NaHS, but not the expressions of mSCF and c-kit. CONCLUSIONS:
      The down regulation of endogenous H(2)S biosynthesis is related to over
      expression of TNF-alpha in obstructed small intestine. TNF-alpha-mediated mSCF
      down-regulation is not the only reason of partial intestinal obstruction-induced
      loss of ICC.

PMID- 23133624
TI  - Hospital readmission prevalence and analysis of those potentially avoidable in
      southern Italy.
AB  - BACKGROUND: One quality indicator of hospital care, which can be used to judge
      the process of care, is the prevalence of hospital readmission because it
      reflects the impact of hospital care on the patient's condition after discharge.
      The purposes of the study were to measure the prevalence of hospital
      readmissions, to identify possible factors that influence such readmission and to
      measure the prevalence of readmissions potentially avoidable in Italy. METHODS: A
      sample of 2289 medical records of patients aged 18 and over admitted for medical
      or surgical illness at one 502-bed community non-teaching hospital were randomly
      selected. RESULTS: A total of 2252 patients were included in the final analysis,
      equaling a response rate of 98.4%. The overall hospital readmission prevalence
      within 30 days of discharge was 10.2%. Multivariate logistic regression analysis
      revealed that the proportion of patients readmitted within 30 days of discharge
      significantly increased regardless of Charlson et al. comorbidity score, among
      unemployed or retired patients, and in patients in general surgery. A total of
      43.7% hospital readmissions were judged to be potentially avoidable. Multivariate
      logistic regression analysis showed that potentially avoidable readmissions were
      significantly higher in general surgery, in patients referred to hospital by an
      emergency department physician, and in those with a shortened time between
      discharge and readmission. CONCLUSION: Additional research on intervention or
      bundle of interventions applicable to acute inpatient populations that aim to
      reduce potentially avoidable readmissions is strongly needed, and health care
      providers are urged to implement evidence-based programs for more cost-effective
      delivery of health care.

PMID- 23133625
TI  - Co-consumption of methanol and succinate by Methylobacterium extorquens AM1.
AB  - Methylobacterium extorquens AM1 is a facultative methylotrophic
      Alphaproteobacterium and has been subject to intense study under pure
      methylotrophic as well as pure heterotrophic growth conditions in the past. Here,
      we investigated the metabolism of M. extorquens AM1 under mixed substrate
      conditions, i.e., in the presence of methanol plus succinate. We found that both
      substrates were co-consumed, and the carbon conversion was two-thirds from
      succinate and one-third from methanol relative to mol carbon. (13)C-methanol
      labeling and liquid chromatography mass spectrometry analyses revealed the
      different fates of the carbon from the two substrates. Methanol was primarily
      oxidized to CO(2) for energy generation. However, a portion of the methanol
      entered biosynthetic reactions via reactions specific to the one-carbon carrier
      tetrahydrofolate. In contrast, succinate was primarily used to provide precursor
      metabolites for bulk biomass production. This work opens new perspectives on the
      role of methylotrophy when substrates are simultaneously available, a situation
      prevailing under environmental conditions.

PMID- 23133626
TI  - High-resolution linkage analyses to identify genes that influence Varroa
      sensitive hygiene behavior in honey bees.
AB  - Varroa mites (V. destructor) are a major threat to honey bees (Apis melilfera)
      and beekeeping worldwide and likely lead to colony decline if colonies are not
      treated. Most treatments involve chemical control of the mites; however, Varroa
      has evolved resistance to many of these miticides, leaving beekeepers with a
      limited number of alternatives. A non-chemical control method is highly desirable
      for numerous reasons including lack of chemical residues and decreased likelihood
      of resistance. Varroa sensitive hygiene behavior is one of two behaviors
      identified that are most important for controlling the growth of Varroa
      populations in bee hives. To identify genes influencing this trait, a study was
      conducted to map quantitative trait loci (QTL). Individual workers of a backcross
      family were observed and evaluated for their VSH behavior in a mite-infested
      observation hive. Bees that uncapped or removed pupae were identified. The
      genotypes for 1,340 informative single nucleotide polymorphisms were used to
      construct a high-resolution genetic map and interval mapping was used to analyze
      the association of the genotypes with the performance of Varroa sensitive
      hygiene. We identified one major QTL on chromosome 9 (LOD score = 3.21) and a
      suggestive QTL on chromosome 1 (LOD = 1.95). The QTL confidence interval on
      chromosome 9 contains the gene 'no receptor potential A' and a dopamine receptor.
      'No receptor potential A' is involved in vision and olfaction in Drosophila, and
      dopamine signaling has been previously shown to be required for aversive
      olfactory learning in honey bees, which is probably necessary for identifying
      mites within brood cells. Further studies on these candidate genes may allow for
      breeding bees with this trait using marker-assisted selection.

PMID- 23133627
TI  - MicroRNA-574-5p was pivotal for TLR9 signaling enhanced tumor progression via
      down-regulating checkpoint suppressor 1 in human lung cancer.
AB  - Accumulating data suggested that functional expression of Toll-like receptors
      (TLRs) in tumor cells was involved in tumor progression. Our previous study
      demonstrated that TLR9 signaling could enhance the tumor progression of human
      lung cancer cells in vitro and in vivo. We further showed that miR-574-5p was the
      mostly up-regulated miRNA in human lung cancer cells under TLR9 signaling by
      miRNA array analysis. Here we characterized the potential role of miRNA-574-5p in
      enhanced tumor progression induced by TLR9 signaling in human lung cancer. We
      confirmed that TLR9 signaling effectively elevated the expression of miR-574-5p
      in human lung cancer cells. Notably, we found that down-regulation of miRNA-574
      5p using miR-574-5p inhibitor in vitro or miR-574-5p sponge in vivo significantly
      abrogated the enhanced tumor progression induced by TLR9 signaling. Further
      studies showed that miR-574-5p was an important player associated with enhanced
      tumor progression of human lung cancer cells. Notably, we identified checkpoint
      suppressor 1 (Ches1) as the dominant direct target for miRNA-574-5p to confer the
      TLR9 signaling enhanced tumor progression. We revealed that over-expression of
      Ches1 significantly inhibited the cell cycle entry of human lung cancer cells.
      Finally, we revealed that the expression of miR-574-5p was positively correlated
      with TLR9 and reversely correlated with Ches1 in lung cancer patients. Our
      findings not only facilitated the further understanding of the crosstalk between
      miRNAs and TLRs in tumor biology, but also provided novel potential candidates
      for treatment of cancer.

PMID- 23133628
TI  - The representation of risk in routine medical experience: what actions for
      contemporary health policy?
AB  - BACKGROUND: The comprehension of appropriate information about illnesses and
      treatments, can have beneficial effects on patients' satisfaction and on
      important health outcomes. However, it is questionable whether people are able to
      understand risk properly. AIM: To describe patients' representation of risk in
      common medical experiences by linking such a representation to the concept of
      trust. A further goal was to test whether the representation of risk in the
      medical domain is associated to the level of expertise. The third goal was to
      verify whether socio-demographic differences influence the representation of
      risk. METHODS: Eighty voluntary participants from 6 health-centers in northern
      Italy were enrolled to conduct a semi-structured interview which included
      demographic questions, term-associations about risk representation, closed and
      open questions about attitudes and perception of risk in the medical context, as
      well as about medical expertise and trust. RESULTS: The results showed that
      people do not have in mind a scientific definition of risk in medicine. Risk is
      seen as a synonym for surgery and disease and it is often confused with fear.
      However, general knowledge of medical matters helps people to have a better
      health management through risk identification and risk information, adoption of
      careful behaviors and tendency to have a critical view about safety and medical
      news. Finally, trust proved to be an important variable in risk representation
      and risk and trust were correlated positively. CONCLUSIONS: People must receive
      appropriate information about the risks and benefits of treatment, in a form that
      they can understand and apply to their own circumstances. Moreover, contemporary
      health policy should empower patients to adopt an active self-care attitude.
      Methodologies to enhance people's decision-making outcomes based on better risk
      communication should be improved in order to enable low literacy population as
      well elderly people to better understand their treatment and associated risk.

PMID- 23133629
TI  - Distribution and quantification of antibiotic resistant genes and bacteria across
      agricultural and non-agricultural metagenomes.
AB  - There is concern that antibiotic resistance can potentially be transferred from
      animals to humans through the food chain. The relationship between specific
      antibiotic resistant bacteria and the genes they carry remains to be described.
      Few details are known about the ecology of antibiotic resistant genes and
      bacteria in food production systems, or how antibiotic resistance genes in food
      animals compare to antibiotic resistance genes in other ecosystems. Here we
      report the distribution of antibiotic resistant genes in publicly available
      agricultural and non-agricultural metagenomic samples and identify which bacteria
      are likely to be carrying those genes. Antibiotic resistance, as coded for in the
      genes used in this study, is a process that was associated with all natural,
      agricultural, and human-impacted ecosystems examined, with between 0.7 to 4.4% of
      all classified genes in each habitat coding for resistance to antibiotic and
      toxic compounds (RATC). Agricultural, human, and coastal-marine metagenomes have
      characteristic distributions of antibiotic resistance genes, and different
      bacteria that carry the genes. There is a larger percentage of the total genome
      associated with antibiotic resistance in gastrointestinal-associated and
      agricultural metagenomes compared to marine and Antarctic samples. Since
      antibiotic resistance genes are a natural part of both human-impacted and
      pristine habitats, presence of these resistance genes in any specific habitat is
      therefore not sufficient to indicate or determine impact of anthropogenic
      antibiotic use. We recommend that baseline studies and control samples be taken
      in order to determine natural background levels of antibiotic resistant bacteria
      and/or antibiotic resistance genes when investigating the impacts of veterinary
      use of antibiotics on human health. We raise questions regarding whether the
      underlying biology of each type of bacteria contributes to the likelihood of
      transfer via the food chain.

PMID- 23133630
TI  - The relationship between the severity of coronary artery disease and epicardial
      adipose tissue depends on the left ventricular function.
AB  - BACKGROUND: Epicardial adipose tissue (EAT) is an active metabolic and endocrine
      organ. Previous studies focusing mainly on patients with preserved left
      ventricular function (LVF) could show a correlation between increased amounts of
      EAT and the extent and activity of coronary artery disease (CAD). However, to
      date, there are no data available about the relationship between EAT and the
      severity of CAD with respect to the whole spectrum of LVF impairment. Therefore,
      we evaluated this relationship in patients with CAD. METHODS: 250 patients with
      CAD and 50 healthy controls underwent CMR examination to assess EAT. The severity
      of CAD was defined using the angiographic Gensini score (GSS). RESULTS: The GSS
      ranged from 2-364. Linear regression analysis revealed a significant correlation
      between EAT and GSS (r = 0.177, p = 0.01). Patients with mild (GSS<=10) and
      moderate CAD (GSS>10-<=40) showed comparable EAT to healthy controls. However, in
      patients with severe CAD (GSS>40) EAT was significantly reduced (p<0.0001)
      compared to healthy controls. Interestingly, patients with the same GSS revealed
      different EAT depending on the left ventricular function (LVF). Patients with
      preserved LVF (LVF>=50%) showed more EAT mass compared to those with reduced LVF
      (LVF<50%) regardless of the GSS. In patients with preserved LVF and mild CAD, EAT
      was comparable to healthy controls (61.8+/-19.4 g vs. 62.9+/-14.4 g, p = 0.8). In
      patients with moderate CAD, EAT rose significantly to 83.1+/-24.9 g (p = 0.01)
      and started to decline to 66.4+/-23.6 g in patients with severe CAD (p = 0.03).
      Contrary, in CAD patients with reduced LVF, EAT was already significantly reduced
      in patients with mild CAD as compared to healthy controls (p = 0.001) and showed
      a stepwise decline with increasing CAD severity. CONCLUSION: The relationship
      between EAT and the severity of CAD depends on LVF. These findings emphasize the
      multifactorial interaction between EAT and the severity of CAD.

PMID- 23133631
TI  - Tumor volume as an alternative response measurement for imatinib treated GIST
      patients.
AB  - BACKGROUND: Assessment of tumor size changes is crucial in clinical trials and
      patient care. We compared imatinib-induced volume changes of liver metastases
      (LM) from gastro-intestinal stromal tumors (GIST) to RECIST and Choi criteria and
      their association with overall survival (OS). METHODS: LM from 84 GIST patients
      (training and validation set) were evaluated using manual and semi-automated
      Computed Tomography measurements at baseline, after 3, 6 and 12 months of
      imatinib. The ability of uni-dimensional (1D) and three-dimensional (3D)
      measurements to detect size changes (increase/decrease) >=20% was evaluated.
      Volumetric response cut-offs were derived from minimally relevant changes (+20/
      30%) by RECIST, considering lesions as spherical or ellipsoidal. RESULTS: 3D
      measurements detected size changes >=20% more frequently than 1D at every time
      point (P<=0.008). 3D and Choi criteria registered more responses than RECIST at 3
      and 6 months for 3D-spheres (P<=0.03) and at all time-points for 3D-ellipsoids
      and Choi criteria (P<0.001). Progressive disease by 3D criteria seems to better
      correlate to OS at late time-points than other criteria. CONCLUSION: Volume
      criteria (especially ellipsoids) classify a higher number of patients as imatinib
      responders than RECIST. Volume discriminates size changes better than diameter in
      GIST and constitutes a feasible and robust method to evaluate response and
      predict patient benefit.

PMID- 23133632
TI  - Selective constraint on the upstream open reading frames that overlap with coding
      sequences in animals.
AB  - Upstream open reading frames (uORFs) are translational regulatory elements
      located in 5' untranslated regions. They can significantly repress the
      translation of the downstream coding sequences (CDS), and participate in the
      spatio-temporal regulations of protein translation. Notwithstanding this
      biological significance, the selective constraint on uORFs remains underexplored.
      Particularly, the uORFs that partially overlap with CDS with a different reading
      frame (overlapping uORFs, or "VuORFs") may lead to strong translational
      inhibition or N-terminal truncation of the peptides encoded by the affected CDS.
      By analyzing VuORF-containing transcripts (designated as "VuORF transcripts") in
      human, mouse, and fruit fly, we demonstrate that VuORFs are in general slightly
      deleterious--the proportion of genes that encode at least one VuORF transcript is
      significantly smaller than expected in all of the three examined species. In
      addition, this proportion is significantly smaller in fruit fly than in mammals,
      indicating a higher efficiency of removing VuORFs in the former species because
      of its larger effective population size. Furthermore, the deleterious effect of a
      VuORF depends on the sequence context of its start codon (VuAUG). VuORFs with an
      optimal VuAUG context are more strongly disfavored than those with a suboptimal
      context in all of the three examined species. And the propensity to remove
      optimal-context VuAUGs is stronger in fruit fly than in mammals. Intriguingly,
      however, the currently observable optimal-context VuAUGs (but not suboptimal
      context VuAUGs) are more conserved than expected. These observations suggest that
      the regulatory functions of VuORFs may have been gained fortuitously in organisms
      with a small effective population size because the slightly deleterious effect of
      these elements can be better tolerated in these organisms, thus allowing
      opportunities for the development of novel biological functions. Nevertheless,
      once the functions of VuORFs were established, they became subject to negative
      selection.

PMID- 23133634
TI  - TamiR159 directed wheat TaGAMYB cleavage and its involvement in anther
      development and heat response.
AB  - In Arabidopsis and rice, miR159-regulated GAMYB-like family transcription factors
      function in flower development and gibberellin (GA) signaling in cereal aleurone
      cells. In this study, the involvement of miR159 in the regulation of its putative
      target TaGAMYB and its relationship to wheat development were investigated.
      First, we demonstrated that cleavage of TaGAMYB1 and TaGAMYB2 was directed by
      miR159 using 5'-RACE and a transient expression system. Second, we overexpressed
      TamiR159, TaGAMYB1 and mTaGAMYB1 (impaired in the miR159 binding site) in
      transgenic rice, revealing that the accumulation in rice of mature miR159 derived
      from the precursor of wheat resulted in delayed heading time and male sterility.
      In addition, the number of tillers and primary branches in rice overexpressing
      mTaGAMYB1 increased relative to the wild type. Our previous study reported that
      TamiR159 was downregulated after two hours of heat stress treatment in wheat
      (Triticum aestivum L.). Most notably, the TamiR159 overexpression rice lines were
      more sensitive to heat stress relative to the wild type, indicating that the
      downregulation of TamiR159 in wheat after heat stress might participate in a heat
      stress-related signaling pathway, in turn contributing to heat stress tolerance.

PMID- 23133633
TI  - A subtype-specific critical period for neurogenesis in the postnatal development
      of mouse olfactory glomeruli.
AB  - Sensory input is essential for the normal development of sensory centers in the
      brain, such as the somatosensory, visual, auditory, and olfactory systems. Visual
      deprivation during a specific developmental stage, called the critical period,
      results in severe and irreversible functional impairments in the primary visual
      cortex. Olfactory deprivation in the early postnatal period also causes
      significant developmental defects in the olfactory bulb, the primary center for
      olfaction. Olfactory bulb interneurons are continuously generated from neural
      stem cells in the ventricular-subventricular zone, suggesting that the olfactory
      system has plasticity even in adulthood. Here, we investigated the effect of
      transient neonatal olfactory deprivation on the addition of interneurons to the
      glomerular layer of the adult mouse olfactory bulb. We found that the addition of
      one subtype of interneurons was persistently inhibited even after reopening the
      naris. BrdU pulse-chase experiments revealed that the neonatal olfactory
      deprivation predominantly affected an early phase in the maturation of this
      neuronal subtype in the olfactory bulb. Subjecting the mice to odor stimulation
      for 6 weeks after naris reopening resulted in significant recovery from the
      histological and functional defects caused by the olfactory deprivation. These
      results suggest that a subtype-specific critical period exists for olfactory bulb
      neurogenesis, but that this period is less strict and more plastic compared with
      the critical periods for other systems. This study provides new insights into the
      mechanisms of postnatal neurogenesis and a biological basis for the therapeutic
      effect of olfactory training.

PMID- 23133635
TI  - Development of a novel fluorophore for real-time biomonitoring system.
AB  - Rapid in-field diagnosis is very important to prevent the outbreak of various
      infectious and contagious diseases. Highly sensitive and quantitative detection
      of diseases can be performed using fluorescent immunochemical assay with specific
      antigen-antibody binding and a good quality fluorophore. This can lead to the
      development of a small, portable, quantitative biosensor to transmit diagnostic
      results to a control center in order to systematically prevent disease outbreaks.
      In this study, we developed a novel fluorophore, coumarin-derived dendrimer, with
      high emission intensity, strong signal brightness, and high photostability. It is
      easily coupled with biomolecules and emits strong and stable fluorescence at 590
      nm with excitation at 455 nm. Application to fluorescent immunochromatographic
      test (FICT) showed that the novel coumarin-derived dendrimer bioconjugate could
      detect antigens at amount as low as 0.1 ng. The clinical results and the spectral
      characteristics of the novel coumarin-derived dendrimer open, for the first time,
      the possibility of developing a cost/energy efficient LED-based portable
      quantitative biosensor for point-of-care (POC) disease diagnosis, which can
      permit real time monitoring (U-healthcare system) by a disease control center.

PMID- 23133636
TI  - Doxorubicin influences the expression of glucosylceramide synthase in invasive
      ductal breast cancer.
AB  - INTRODUCTION: Glucosylceramide synthase (GCS) is one enzyme that provides a major
      route for ceramide clearance. Recent evidence has indicated an important role for
      GCS in multidrug resistance (MDR) tumors. Doxorubicin (DOX)can modulate the
      expression of GCS in leukemia and ovary cell lines. However, few studies have
      investigated their relationship in breast cancer; METHODS: We collected 84
      excision biopsies from patients with invasive ductal breast cancer of whom 33
      patients had undergone preoperative chemotherapy. Immunohistochemistry was used
      to analyze the expression of GCS protein and significantly showed that the
      expression of GCS was higher in the samples from patients treated with
      preoperative chemotherapy(p = 0.018). In order to investigate the underlying
      mechanism, breast cancer cell lines were cultured with different concentrations
      of DOX, and mRNA and protein levels of GCS were then detected; RESULTS: DOX
      significantly upregulated the expression of GCS at both the mRNA and protein
      level in ERalpha-positive MCF-7 cells.We then block down the Sp1 site of GCS
      promoter, which inhibited the DOX-mediated increase in GCS expression; and after
      Eralpha was inhibited in MCF-7 cells, the up-regulation of GCS by DOX also been
      inhibited. CONCLUSIONS: In conclusion, our data demonstrated the novel finding
      that DOX could modulate the expression of GCS through the Sp1 site of GCS
      promoter in ERalpha-positive breast cancer cells.

PMID- 23133637
TI  - Metagenomic analysis of the microbiota from the crop of an invasive snail reveals
      a rich reservoir of novel genes.
AB  - The shortage of petroleum reserves and the increase in CO(2) emissions have
      raised global concerns and highlighted the importance of adopting sustainable
      energy sources. Second-generation ethanol made from lignocellulosic materials is
      considered to be one of the most promising fuels for vehicles. The giant snail
      Achatina fulica is an agricultural pest whose biotechnological potential has been
      largely untested. Here, the composition of the microbial population within the
      crop of this invasive land snail, as well as key genes involved in various
      biochemical pathways, have been explored for the first time. In a high-throughput
      approach, 318 Mbp of 454-Titanium shotgun metagenomic sequencing data were
      obtained. The predominant bacterial phylum found was Proteobacteria, followed by
      Bacteroidetes and Firmicutes. Viruses, Fungi, and Archaea were present to lesser
      extents. The functional analysis reveals a variety of microbial genes that could
      assist the host in the degradation of recalcitrant lignocellulose, detoxification
      of xenobiotics, and synthesis of essential amino acids and vitamins, contributing
      to the adaptability and wide-ranging diet of this snail. More than 2,700 genes
      encoding glycoside hydrolase (GH) domains and carbohydrate-binding modules were
      detected. When we compared GH profiles, we found an abundance of sequences coding
      for oligosaccharide-degrading enzymes (36%), very similar to those from wallabies
      and giant pandas, as well as many novel cellulase and hemicellulase coding
      sequences, which points to this model as a remarkable potential source of enzymes
      for the biofuel industry. Furthermore, this work is a major step toward the
      understanding of the unique genetic profile of the land snail holobiont.

PMID- 23133638
TI  - Artificial theta stimulation impairs encoding of contextual fear memory.
AB  - Several experiments have demonstrated an intimate relationship between
      hippocampal theta rhythm (4-12 Hz) and memory. Lesioning the medial septum or
      fimbria-fornix, a fiber track connecting the hippocampus and the medial septum,
      abolishes the theta rhythm and results in a severe impairment in declarative
      memory. To assess whether there is a causal relationship between hippocampal
      theta and memory formation we investigated whether restoration of hippocampal
      theta by electrical stimulation during the encoding phase also restores fimbria
      fornix lesion induced memory deficit in rats in the fear conditioning paradigm.
      Male Wistar rats underwent sham or fimbria-fornix lesion operation. Stimulation
      electrodes were implanted in the ventral hippocampal commissure and recording
      electrodes in the septal hippocampus. Artificial theta stimulation of 8 Hz was
      delivered during 3-min free exploration of the test cage in half of the rats
      before aversive conditioning with three foot shocks during 2 min. Memory was
      assessed by total freezing time in the same environment 24 h and 28 h after fear
      conditioning, and in an intervening test session in a different context. As
      expected, fimbria-fornix lesion impaired fear memory and dramatically attenuated
      hippocampal theta power. Artificial theta stimulation produced continuous theta
      oscillations that were almost similar to endogenous theta rhythm in amplitude and
      frequency. However, contrary to our predictions, artificial theta stimulation
      impaired conditioned fear response in both sham and fimbria-fornix lesioned
      animals. These data suggest that restoration of theta oscillation per se is not
      sufficient to support memory encoding after fimbria-fornix lesion and that
      universal theta oscillation in the hippocampus with a fixed frequency may
      actually impair memory.

PMID- 23133639
TI  - A quantitative and novel approach to the prioritization of zoonotic diseases in
      North America: a public perspective.
AB  - BACKGROUND: Zoonoses account for over half of all communicable diseases causing
      illness in humans. As there are limited resources available for the control and
      prevention of zoonotic diseases, a framework for their prioritization is
      necessary to ensure resources are directed into those of highest importance.
      Although zoonotic outbreaks are a significant burden of disease in North America,
      the systematic prioritization of zoonoses in this region has not been previously
      evaluated. METHODOLOGY/PRINCIPAL FINDINGS: This study describes the novel use of
      a well-established quantitative method, conjoint analysis (CA), to identify the
      relative importance of 21 key characteristics of zoonotic diseases that can be
      used for their prioritization in Canada and the US. Relative importance weights
      from the CA were used to develop a point-scoring system to derive a recommended
      list of zoonoses for prioritization in Canada and the US. Over 1,500 participants
      from the general public were recruited to complete the online survey (761 from
      Canada and 778 from the US). Hierarchical Bayes models were fitted to the survey
      data to derive CA-weighted scores. Scores were applied to 62 zoonotic diseases of
      public health importance in Canada and the US to rank diseases in order of
      priority. CONCLUSIONS/SIGNIFICANCE: This was the first study to describe a
      systematic and quantitative approach to the prioritization of zoonoses in North
      America involving public participants. We found individuals with no prior
      knowledge or experience in prioritizing zoonoses were capable of producing
      meaningful results using CA as a novel quantitative approach to prioritization.
      More similarities than differences were observed between countries suggesting
      general agreement in disease prioritization between Canadians and Americans. We
      demonstrate CA as a potential tool for the prioritization of zoonoses; other
      prioritization exercises may also consider this approach.

PMID- 23133640
TI  - Diabetic HDL is dysfunctional in stimulating endothelial cell migration and
      proliferation due to down regulation of SR-BI expression.
AB  - BACKGROUND: Diabetic HDL had diminished capacity to stimulate endothelial cell
      (EC) proliferation, migration, and adhesion to extracellular matrix. The
      mechanism of such dysfunction is poorly understood and we therefore sought to
      determine the mechanistic features of diabetic HDL dysfunction.
      METHODOLOGY/PRINCIPAL FINDINGS: We found that the dysfunction of diabetic HDL on
      human umbilical vein endothelial cells (HUVECs) was associated with the down
      regulation of the HDL receptor protein, SR-BI. Akt-phosphorylation in HUVECs was
      induced in a biphasic manner by normal HDL. While diabetic HDL induced Akt
      phosphorylation normally after 20 minutes, the phosphorylation observed 24 hours
      after diabetic HDL treatment was reduced. To determine the role of SR-BI down
      regulation on diminished EC responses of diabetic HDL, Mouse aortic endothelial
      cells (MAECs) were isolated from wild type and SR-BI (-/-) mice, and treated with
      normal and diabetic HDL. The proliferative and migratory effects of normal HDL on
      wild type MAECs were greatly diminished in SR-BI (-/-) cells. In contrast,
      response to diabetic HDL was impaired in both types suggesting diminished
      effectiveness of diabetic HDL on EC proliferation and migration might be due to
      the down regulation of SR-BI. Additionally, SR-BI down regulation diminishes
      diabetic HDL's capacity to activate Akt chronically. CONCLUSIONS/SIGNIFICANCE:
      Diabetic HDL was dysfunctional in promoting EC proliferation, migration, and
      adhesion to matrix which was associated with the down-regulation of SR-BI.
      Additionally, SR-BI down regulation diminishes diabetic HDL's capacity to
      activate Akt chronically.

PMID- 23133641
TI  - A peptide binding to the beta-site of APP improves spatial memory and attenuates
      Abeta burden in Alzheimer's disease transgenic mice.
AB  - Amyloid precursor protein cleaving enzyme 1 (BACE1), an aspartyl protease,
      initiates processing of the amyloid precursor protein (APP) into beta-amyloid
      (Abeta); the peptide likely contributes to development of Alzheimer's disease
      (AD). BACE1 is an attractive therapeutic target for AD treatment, but it exhibits
      other physiological activities and has many other substrates besides APP. Thus,
      inhibition of BACE1 function may cause adverse side effects. Here, we present a
      peptide, S1, isolated from a peptide library that selectively inhibits BACE1
      hydrolytic activity by binding to the beta-proteolytic site on APP and Abeta N
      terminal. The S1 peptide significantly reduced Abeta levels in vitro and in vivo
      and inhibited Abeta cytotoxicity in SH-SY5Y cells. When applied to APPswe/PS1dE9
      double transgenic mice by intracerebroventricular injection, S1 significantly
      improved the spatial memory as determined by the Morris Water Maze, and also
      attenuated their Abeta burden. These results indicate that the dual-functional
      peptide S1 may have therapeutic potential for AD by both reducing Abeta
      generation and inhibiting Abeta cytotoxicity.

PMID- 23133642
TI  - The association between KCNQ1 gene polymorphism and type 2 diabetes risk: a meta
      analysis.
AB  - BACKGROUND: KCNQ1 (potassium voltage-gated channel KQT-like sub-family, member 1)
      encodes a pore-forming subunit of a voltage-gated K(+) channel (KvLQT1) that
      plays a key role for the repolarization of the cardiac action potential as well
      as water and salt transport in epithelial tissues. Recently, genome-wide
      association studies have identified KCNQ1 as a type 2 diabetes (T2D)
      susceptibility gene in populations of Asian descent. After that, a number of
      studies reported that the rs2237892 and rs2237895 polymorphism in KCNQ1 has been
      implicated in T2D risk. However, studies on the association between these
      polymorphism and T2D remain conflicting. To investigate this inconsistency, we
      performed this meta-analysis. METHODS: Databases including Pubmed, EMBASE, Web of
      Science and China National Knowledge Infrastructure (CNKI) were searched to find
      relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used
      to assess the strength of association. Potential sources of heterogeneity were
      also assessed by subgroup analysis and meta-regression. RESULTS: A total of 25
      articles involving 70,577 T2D cases and 99,068 controls were included. Overall,
      the summary odds ratio of C allele for T2D was 1.32 (95% CI 1.26-1.38; P<10-5)
      and 1.24 (95% CI: 1.20-1.29; P<10-5) for KCNQ1 rs2237892 and rs2237895
      polymorphisms, respectively. Significant results were also observed using co
      dominant, dominant and recessive genetic models. After stratifying by ethnicity,
      sample size, and diagnostic criteria, significant associations were also
      obtained. CONCLUSIONS: This meta-analysis suggests that the rs2237892 and
      rs2237895 polymorphisms in KCNQ1 are associated with elevated type 2 diabetes
      susceptibility.

PMID- 23133643
TI  - Defining the cause of death in hospitalised patients with acute kidney injury.
AB  - BACKGROUND: The high mortality rates that follow the onset of acute kidney injury
      (AKI) are well recognised. However, the mode of death in patients with AKI
      remains relatively under-studied, particularly in general hospitalised
      populations who represent the majority of those affected. We sought to describe
      the primary cause of death in a large group of prospectively identified patients
      with AKI. METHODS: All patients sustaining AKI at our centre between 1(st)
      October 2010 and 31(st) October 2011 were identified by real-time, hospital-wide,
      electronic AKI reporting based on the Acute Kidney Injury Network (AKIN)
      diagnostic criteria. Using this system we are able to generate a prospective
      database of all AKI cases that includes demographic, outcome and hospital coding
      data. For those patients that died during hospital admission, cause of death was
      derived from the Medical Certificate of Cause of Death. RESULTS: During the study
      period there were 3,930 patients who sustained AKI; 62.0% had AKI stage 1, 20.6%
      had stage 2 and 17.4% stage 3. In-hospital mortality rate was 21.9% (859
      patients). Cause of death could be identified in 93.4% of cases. There were three
      main disease categories accounting for three quarters of all mortality; sepsis
      (41.1%), cardiovascular disease (19.2%) and malignancy (12.9%). The major
      diagnosis leading to sepsis was pneumonia, whilst cardiovascular death was
      largely a result of heart failure and ischaemic heart disease. AKI was the
      primary cause of death in only 3% of cases. CONCLUSIONS: Mortality associated
      with AKI remains high, although cause of death is usually concurrent illness.
      Specific strategies to improve outcomes may therefore need to target not just the
      management of AKI but also the most relevant co-existing conditions.

PMID- 23133644
TI  - HIF-1alpha inhibition reduces nasal inflammation in a murine allergic rhinitis
      model.
AB  - BACKGROUND: Hypoxia-inducible factor 1alpha (HIF-1alpha) is an important
      regulator of immune and inflammatory responses. We hypothesized that nasal
      allergic inflammation is attenuated by HIF-1alpha inhibition and strengthened by
      HIF-1alpha stabilization. OBJECTIVE: To elucidate the role of HIF-1alpha in a
      murine model of allergic rhinitis (AR). METHODS: Mice were pretreated with the
      HIF-1alpha inhibitor 2-methoxyestradiol (2ME2) or the HIF-1alpha inducer cobalt
      chloride (CoCl(2)) in an established AR murine model using ovalbumin (OVA)
      sensitized BALB/c mice. HIF-1alpha and vascular endothelial growth factor (VEGF)
      expression in nasal mucosa was measured and multiple parameters of allergic
      responses were evaluated. RESULTS: HIF-1alpha and VEGF levels were locally up
      regulated in nasal mucosa during AR. Inflammatory responses to OVA challenge,
      including nasal symptoms, inflammatory cell infiltration, eosinophil recruitment,
      up-regulation of T-helper type 2 cytokines in nasal lavage fluid, and serum OVA
      specific IgE levels were present in the OVA-challenged mice. 2ME2 effectively
      inhibited HIF-1alpha and VEGF expression and attenuated the inflammatory
      responses. Stabilization of HIF-1alpha by CoCl(2) facilitated nasal allergic
      inflammation. HIF-1alpha protein levels in nasal airways correlated with the
      severity of AR in mice. CONCLUSIONS: HIF-1alpha is intimately involved in the
      pathogenesis of nasal allergies, and the inhibition of HIF-1alpha may be useful
      as a novel therapeutic approach for AR.

PMID- 23133645
TI  - The interactive effect of SIRT1 promoter region polymorphism on type 2 diabetes
      susceptibility in the North Indian population.
AB  - Our previous studies have implicated genes mainly involved in the activity of
      pancreatic beta cells in type 2 diabetes (T2D) susceptibility in the North Indian
      population. Recent literature on the role of SIRT1 as a potential master switch
      modulating insulin secretion and regulating gene expression in pancreatic beta
      cells has warranted an evaluation of SIRT1 promoter region polymorphisms in the
      North Indian population, which is the main focus of the present study. 1542
      samples (692 T2D patients and 850 controls) were sequenced for the 1.46 kb region
      upstream the translation start site of the SIRT1 gene. We performed a functional
      characterization of the SIRT1 promoter region polymorphisms using luciferase
      assay and observed a single-nucleotide polymorphism (SNP), rs12778366, in
      association with SIRT1 expression. We propose that TT, the high-expressing
      genotype of SNP rs12778366 in the SIRT1 promoter region and present in >80% of
      the North Indian population, was favored under conditions of feast-famine cycles
      in evolution, which has turned out to be a cause of concern in the present
      sedentary lifestyle under ad libitum conditions. Case-control association
      analysis did not implicate rs12778366 in T2DM per se in the studied population.
      However, our earlier reported risk genotype combinations of mt-ND3, PGC1alpha,
      and UCP2-866, when compared with the protective genotype combinations, in the
      background of the high-expressing TT genotype of SIRT1 SNP rs12778366, showed a
      very high additive risk [corrected odd ratio (OR) = 8.91; p = 6.5*10(-11)]. The
      risk level was considerably low in the genotype backgrounds of TX (OR = 6.68; p =
      2.71*10(-12)) and CX (OR = 3.74; p = 4.0*10(-3)). In addition, we screened other
      reported T2D-associated polymorphisms: PIK3R1 rs3730089, IRS1 rs1801278, and
      PPP1R3 rs1799999, which did not show any significant association in North Indian
      population. The present paper emphasizes the importance of gene interactions in
      the biological pathways of T2D, a complex lifestyle disease.

PMID- 23133646
TI  - MicroRNAs differentially regulate carbonyl reductase 1 (CBR1) gene expression
      dependent on the allele status of the common polymorphic variant rs9024.
AB  - MicroRNAs (miRNAs) are small RNAs responsible for the post-transcriptional
      regulation of a variety of human genes. To date, their involvement in the
      regulation of CBR1 is unknown. This study reports for the first time the
      identification of microRNA-574-5p (hsa-miR-574-5p) and microRNA-921 (hsa-miR-921)
      as two miRNAs capable of interacting with the 3'-untranslated region (3'-UTR) of
      the CBR1 gene and downregulating CBR1 expression. Furthermore, we demonstrate
      that a common single-nucleotide polymorphism (SNP) in the CBR1 3'-UTR (rs9024,
      CBR1 1096G>A) differentially impacts the regulation of CBR1 by hsa-miR-574-5p and
      hsa-miR-921 dependent on genotype. First, four candidate miRNAs were selected
      based on bioinformatic analyses, and were tested in Chinese hamster ovary (CHO)
      cells transfected with CBR1 3'-UTR constructs harboring either the G or A allele
      for rs9024. We found that hsa-miR-574-5p and hsa-miR-921 significantly decreased
      luciferase activity in CHO cells transfected with the CBR1 3'-UTR construct
      carrying the major rs9024 G allele by 35% and 46%, respectively. The influence of
      these miRNAs was different in cells transfected with a CBR1 3'-UTR construct
      containing the minor rs9024 A allele in that only hsa-miR-574-5p had a
      demonstrable effect (i.e., 52% decrease in lucifersase activity). To further
      determine the functional effects of miRNA-mediated regulation of polymorphic
      CBR1, we assessed CBR1 protein expression and CBR1 enzymatic activity for the
      prototypical substrate menadione in human lymphoblastoid cell lines with distinct
      rs9024 genotypes. We found that hsa-miR-574-5p and hsa-miR-921 significantly
      decreased CBR1 protein (48% and 40%, respectively) and CBR1 menadione activity
      (54% and 18%, respectively) in lymphoblastoid cells homozygous for the major
      rs9024 G allele. In contrast, only hsa-miR-574-5p decreased CBR1 protein and CBR1
      activity in cells homozygous for the minor rs9024 A allele, and did so by 49% and
      56%, respectively. These results suggest that regulation of human CBR1 expression
      by hsa-miR-574-5p and hsa-miR-921 depends upon rs9024 genotype status.

PMID- 23133647
TI  - Fibrillin-1 mutations causing Weill-Marchesani syndrome and acromicric and
      geleophysic dysplasias disrupt heparan sulfate interactions.
AB  - The extracellular glycoprotein fibrillin-1 forms microfibrils that act as the
      template for elastic fibers. Most mutations in fibrillin-1 cause Marfan syndrome
      with severe cardiovascular and ocular symptoms, and tall stature. This is in
      contrast to mutations within a heparin-binding TB domain (TB5), which is
      downstream of the arg-gly-asp cell adhesion domain, which can cause Weill
      Marchesani syndrome (WMS) or Acromicric (AD) and Geleophysic Dysplasias (GD). WMS
      is characterized by short limbs, joint stiffness and ocular defects, whilst
      fibrillin-1 AD and GD have severe short stature, joint defects and thickened
      skin. We previously showed that TB5 binds heparin. Here, we show that the
      corresponding region of fibrillin-2 binds heparin very poorly, highlighting a
      novel functional difference between the two isoforms. This finding enabled us to
      map heparin/heparan sulfate binding to two sites on fibrillin-1 TB5 using a
      mutagenesis approach. Once these sites were mapped, we were able to investigate
      whether disease-causing mutations in this domain disrupt binding to HS. We show
      that a WMS deletion mutant, and five AD and GD point mutants all have disrupted
      heparin binding to TB5. These data provide insights into the biology of
      fibrillins and the pathologies of WMS, AD and GD.

PMID- 23133648
TI  - Type II collagen induces peripheral tolerance in BALB/c mice via the generation
      of CD8+ T regulatory cells.
AB  - Antigens introduced into the anterior chamber (AC) of the eye induce a potent
      form of antigen-specific peripheral immune tolerance termed AC-associated immune
      deviation (ACAID), which prevents inflammatory immune responses and is
      characterized by impaired delayed-type hypersensitivity (DTH) responses. Type-II
      collagen (CII) is a fibrillar protein expressed exclusively in cartilage tissues.
      Although of its clinical relevance to Rheumatoid arthritis, aging, and
      osteoarthritis, there have been no studies to date to test if CII has the ability
      to induce ACAID. We hypothesized that ACAID could be generated via AC injection
      of CII in BALB/c mice. Using a DTH assay, the hypothesis was supported and led to
      another hypothesis that CII is capable of inducing specific immune tolerance via
      CD8(+) T regulatory cells (Tregs). Thus, we performed functional local adoptive
      transfer (LAT) assays to examine the regulatory roles of spleen cells, T cells,
      and CD8(+) T cells in the specific immune regulation induced by CII injection
      into the AC. Results indicated that CII induced ACAID when injected into the AC.
      Spleen cells of mice injected with CII in the AC significantly suppressed DTH
      responses. The T cell compartment of the spleen was capable of expressing this
      suppression. CD8(+) Tregs could solely express this CII-driven suppression and
      even exerted more noticeable suppression than spleen cells or splenic T cells.
      This study suggests a crucial role for CD8(+) Tregs in mediating CII-driven ACAID
      mediated immune tolerance. This could have therapeutic implications in Rheumatoid
      arthritis, aging, osteoarthritis, and other diseases in which CII is involved.

PMID- 23133650
TI  - The HIV-1 Rev protein enhances encapsidation of unspliced and spliced, RRE
      containing lentiviral vector RNA.
AB  - BACKGROUND: During the RNA encapsidation process of human immunodeficiency virus
      (HIV) viral genomic, unspliced RNA (gRNA) is preferentially incorporated into
      assembling virions. However, a certain amount of spliced viral transcripts can
      also be detected in viral particles. Recently, we observed that nuclear export of
      HIV and lentiviral vector gRNA by Rev is required for efficient encapsidation.
      Since singly-spliced HIV transcripts also contain the Rev-response element (RRE),
      we investigated if the encapsidation efficiency of RRE-containing spliced HIV
      vector transcripts is also increased by the viral Rev protein. FINDINGS: Starting
      with a lentiviral vector imitating the splicing pattern of HIV, we constructed
      vectors that express an unspliced transcript either identical in sequence to the
      singly-spliced or the fully-spliced RNA of the parental construct. After
      transfection of the different lentiviral vectors cytoplasmic and virion
      associated RNA levels and vector titers were determined in the presence and
      absence of Rev. Rev enhanced the infectious titer of vectors containing an RRE 6
      to 37-fold. Furthermore, Rev strongly increased encapsidation efficiencies of all
      RRE-containing transcripts up to 200-fold. However, a good correlation between
      encapsidation efficiency and lentiviral vector titer could only be observed for
      the gRNA. The infectious titer of the vector encoding the fully-spliced RNA
      without RRE as well as the encapsidation efficiency of all transcripts lacking
      the RRE was not influenced by Rev. Interestingly, the splicing process itself did
      not seem to interfere with packaging, since the encapsidation efficiencies of the
      same RNA expressed either by splicing or as an unspliced transcript did not
      differ significantly. CONCLUSIONS: Rev-mediated nuclear export enhances the
      encapsidation efficiency of RRE-containing lentiviral vector RNAs independently
      of whether they have been spliced or not.

PMID- 23133649
TI  - A nonintegrative lentiviral vector-based vaccine provides long-term sterile
      protection against malaria.
AB  - Trials testing the RTS,S candidate malaria vaccine and radiation-attenuated
      sporozoites (RAS) have shown that protective immunity against malaria can be
      induced and that an effective vaccine is not out of reach. However, longer-term
      protection and higher protection rates are required to eradicate malaria from the
      endemic regions. It implies that there is still a need to explore new vaccine
      strategies. Lentiviral vectors are very potent at inducing strong immunological
      memory. However their integrative status challenges their safety profile.
      Eliminating the integration step obviates the risk of insertional oncogenesis.
      Providing they confer sterile immunity, nonintegrative lentiviral vectors (NILV)
      hold promise as mass pediatric vaccine by meeting high safety standards. In this
      study, we have assessed the protective efficacy of NILV against malaria in a
      robust pre-clinical model. Mice were immunized with NILV encoding Plasmodium
      yoelii Circumsporozoite Protein (Py CSP) and challenged with sporozoites one
      month later. In two independent protective efficacy studies, 50% (37.5-62.5) of
      the animals were fully protected (p = 0.0072 and p = 0.0008 respectively when
      compared to naive mice). The remaining mice with detectable parasitized red blood
      cells exhibited a prolonged patency and reduced parasitemia. Moreover, protection
      was long-lasting with 42.8% sterile protection six months after the last
      immunization (p = 0.0042). Post-challenge CD8+ T cells to CSP, in contrast to
      anti-CSP antibodies, were associated with protection (r = -0.6615 and p = 0.0004
      between the frequency of IFN-g secreting specific T cells in spleen and
      parasitemia). However, while NILV and RAS immunizations elicited comparable
      immunity to CSP, only RAS conferred 100% of sterile protection. Given that a
      better protection can be anticipated from a multi-antigen vaccine and an
      optimized vector design, NILV appear as a promising malaria vaccine.

PMID- 23133651
TI  - The beta1-subunit of Na(v)1.5 cardiac sodium channel is required for a dominant
      negative effect through alpha-alpha interaction.
AB  - Brugada syndrome (BrS) is an inherited autosomal dominant cardiac channelopathy.
      Several mutations on the cardiac sodium channel Na(v)1.5 which are responsible
      for BrS lead to misfolded proteins that do not traffic properly to the plasma
      membrane. In order to mimic patient heterozygosity, a trafficking defective
      mutant, R1432G was co-expressed with Wild Type (WT) Na(v)1.5 channels in HEK293T
      cells. This mutant significantly decreased the membrane Na current density when
      it was co-transfected with the WT channel. This dominant negative effect did not
      result in altered biophysical properties of Na(v)1.5 channels. Luminometric
      experiments revealed that the expression of mutant proteins induced a significant
      reduction in membrane expression of WT channels. Interestingly, we have found
      that the auxiliary Na channel beta(1)-subunit was essential for this dominant
      negative effect. Indeed, the absence of the beta(1)-subunit prevented the
      decrease in WT sodium current density and surface proteins associated with the
      dominant negative effect. Co-immunoprecipitation experiments demonstrated a
      physical interaction between Na channel alpha-subunits. This interaction occurred
      only when the beta(1)-subunit was present. Our findings reveal a new role for
      beta(1)-subunits in cardiac voltage-gated sodium channels by promoting alpha
      alpha subunit interaction which can lead to a dominant negative effect when one
      of the alpha-subunits shows a trafficking defective mutation.

PMID- 23133652
TI  - Protection of rabbits and immunodeficient mice against lethal poxvirus infections
      by human monoclonal antibodies.
AB  - Smallpox (variola virus) is a bioweapon concern. Monkeypox is a growing zoonotic
      poxvirus threat. These problems have resulted in extensive efforts to develop
      potential therapeutics that can prevent or treat potentially lethal poxvirus
      infections in humans. Monoclonal antibodies (mAbs) against smallpox are a
      conservative approach to this problem, as the licensed human smallpox vaccine
      (vaccinia virus, VACV) primarily works on the basis of protective antibody
      responses against smallpox. Fully human mAbs (hmAbs) against vaccinia H3 (H3L)
      and B5 (B5R), targeting both the mature virion (MV) and extracellular enveloped
      virion (EV) forms, have been developed as potential therapeutics for use in
      humans. Post-exposure prophylaxis was assessed in both murine and rabbit animal
      models. Therapeutic efficacy of the mAbs was assessed in three good laboratory
      practices (GLP) studies examining severe combined immunodeficiency mice (SCID)
      given a lethal VACV infection. Pre-exposure combination hmAb therapy provided
      significantly better protection against disease and death than either single hmAb
      or vaccinia immune globulin (VIG). Post-exposure combination mAb therapy provided
      significant protection against disease and death, and appeared to fully cure the
      VACV infection in >=50% of SCID mice. Therapeutic efficacy was then assessed in
      two rabbit studies examining post-exposure hmAb prophylaxis against rabbitpox
      (RPXV). In the first study, rabbits were infected with RPVX and then provided
      hmAbs at 48 hrs post-infection, or 1 hr and 72 hrs post-infection. Rabbits in
      both groups receiving hmAbs were 100% protected from death. In the second
      rabbitpox study, 100% of animal treated with combination hmAb therapy and 100% of
      animals treated with anti-B5 hmAb were protected. These findings suggest that
      combination hmAb treatment may be effective at controlling smallpox disease in
      immunocompetent or immunodeficient humans.

PMID- 23133653
TI  - Polymorphisms in thioredoxin reductase and selenoprotein K genes and selenium
      status modulate risk of prostate cancer.
AB  - Increased dietary intake of Selenium (Se) has been suggested to lower prostate
      cancer mortality, but supplementation trials have produced conflicting results.
      Se is incorporated into 25 selenoproteins. The aim of this work was to assess
      whether risk of prostate cancer is affected by genetic variants in genes coding
      for selenoproteins, either alone or in combination with Se status. 248 cases and
      492 controls from an EPIC-Heidelberg nested case-control study were subjected to
      two-stage genotyping with an initial screening phase in which 384 tagging-SNPs
      covering 72 Se-related genes were determined in 94 cases and 94 controls using
      the Illumina Goldengate methodology. This analysis was followed by a second phase
      in which genotyping for candidate SNPs identified in the first phase was carried
      out in the full study using Sequenom. Risk of high-grade or advanced stage
      prostate cancer was modified by interactions between serum markers of Se status
      and genotypes for rs9880056 in SELK, rs9605030 and rs9605031 in TXNRD2, and
      rs7310505 in TXNRD1. No significant effects of SNPs on prostate cancer risk were
      observed when grade or Se status was not taken into account. In conclusion, the
      risk of high-grade or advanced-stage prostate cancer is significantly altered by
      a combination of genotype for SNPs in selenoprotein genes and Se status. The
      findings contribute to explaining the biological effects of selenium intake and
      genetic factors in prostate cancer development and highlight potential roles of
      thioredoxin reductases and selenoprotein K in tumour progression.

PMID- 23133654
TI  - Extracellular DNA release by undomesticated Bacillus subtilis is regulated by
      early competence.
AB  - Extracellular DNA (eDNA) release is a widespread capacity described in many
      microorganisms. We identified and characterized lysis-independent eDNA production
      in an undomesticated strain of Bacillus subtilis. DNA fragments are released
      during a short time in late-exponential phase. The released eDNA corresponds to
      whole genome DNA, and does not harbour mutations suggesting that is not the
      result of error prone DNA synthesis. The absence of eDNA was linked to a spread
      colony morphology, which allowed a visual screening of a transposon library to
      search for genes involved in its production. Transposon insertions in genes
      related to quorum sensing and competence (oppA, oppF and comXP) and to DNA
      metabolism (mfd and topA) were impaired in eDNA release. Mutants in early
      competence genes such as comA and srfAA were also defective in eDNA while in
      contrast mutations in late competence genes as those for the DNA uptake machinery
      had no effect. A subpopulation of cells containing more DNA is present in the
      eDNA producing strains but absent from the eDNA defective strain. Finally,
      competent B. subtilis cells can be transformed by eDNA suggesting it could be
      used in horizontal gene transfer and providing a rationale for the molecular link
      between eDNA release and early-competence in B. subtilis that we report.

PMID- 23133655
TI  - The altmetrics collection.

PMID- 23133656
TI  - Revealing the hyperdiverse mite fauna of subarctic Canada through DNA barcoding.
AB  - Although mites are one of the most abundant and diverse groups of arthropods,
      they are rarely targeted for detailed biodiversity surveys due to taxonomic
      constraints. We address this gap through DNA barcoding, evaluating acarine
      diversity at Churchill, Manitoba, a site on the tundra-taiga transition. Barcode
      analysis of 6279 specimens revealed nearly 900 presumptive species of mites with
      high species turnover between substrates and between forested and non-forested
      sites. Accumulation curves have not reached an asymptote for any of the three
      mite orders investigated, and estimates suggest that more than 1200 species of
      Acari occur at this locality. The coupling of DNA barcode results with taxonomic
      assignments revealed that Trombidiformes compose 49% of the fauna, a larger
      fraction than expected based on prior studies. This investigation demonstrates
      the efficacy of DNA barcoding in facilitating biodiversity assessments of
      hyperdiverse taxa.

PMID- 23133657
TI  - Human milk sIgA molecules contain various combinations of different antigen
      binding sites resulting in a multiple binding specificity of antibodies and
      enzymatic activities of abzymes.
AB  - In the classic paradigm, immunoglobulins are monospecific molecules that have
      stable structures and two or more identical antigen-binding sites. However, we
      show here for the first time that the sIgA pool of human milk contains, depending
      on the donor, only 35+/-5% lambda-sIgAs, 48+/-7% kappa-sIgAs, and 17+/-4% of
      chimeric lambda-kappa-sIgAs. sIgA preparations contained no traces of canonical
      enzymes. However, all sIgA fractions eluted from several specific affinity
      sorbents under the conditions destroying even strong immune complexes
      demonstrated high catalytic activities in hydrolysis of ATP, DNA, and
      oligosaccharides, and phosphorylation of proteins, lipids, and oligosaccharides.
      Sequential re-chromatographies of the sIgA fractions with high affinity to one
      affinity sorbents on the second, third and then fourth affinity sorbents bearing
      other immobilized antigens led to the distribution of Abs and all catalytic
      activities all over the profiles of these chromatographies; in all cases some
      fractions eluted from affinity sorbents only under the conditions destroying
      strong immune complexes. In vitro, only an addition of reduced glutathione and
      milk plasma containing no Abs to two sIgA fractions with different affinity for
      DNA-cellulose led to a transition of up to 11-20% of Ab from one fraction to the
      other. Our data are indicative of the possibility of half-molecule exchange
      between different IgA and sIgA molecules. In addition, it cannot be excluded that
      during the penetration of IgAs through the specific milk barrier, the secretory
      component (S) and the join chain (J) can combine molecules of dimeric H(2)L(2)
      lambda-IgAs and kappa-IgAs against different antigens forming many different
      variants of H(4)L(4)SJ sIgA molecules. Therefore, some chimeric molecules of sIgA
      can contain from two to four HL-fragments to various antigens interacting with
      high affinity with different sorbents and catalyzing various chemical reactions.
      Our data essentially expand the ideas concerning explanation of the phenomenon of
      polyspecificity and cross-reactivity of Abs.

PMID- 23133658
TI  - Knowledge, attitudes and practices of contraception among Afghan refugee women in
      Pakistan: a cross-sectional study.
AB  - BACKGROUND: During the 1980s, approximately three million people migrated from
      Afghanistan to Pakistan and sought refuge in several cities including the city of
      Karachi. After the initial settlement of the refugees, the international
      organizations transitioned the health care of these refugees to the two local non
      profit service agencies in Karachi. One of these agencies subsidized health care
      to the refugees under their care and the other agency encouraged the refugees
      under their care to utilize governmental and non-governmental private health
      resources at the disposal of general public. Our objective was to measure the
      effect of health subsidy on the uptake of contraception among Afghan refugee
      women and compare them to the group of Afghan women without such a subsidy.
      METHODOLOGY/PRINCIPAL FINDINGS: A randomly selected group of 650 married Afghan
      women--325 women in each group--participated in a detailed survey regarding the
      knowledge, attitude and practices of family planning and contraceptive use. 90
      percent of the women in the health subsidy group had had heard of family
      planning, compared to the 45 percent in the non-subsidized group. The use of
      contraceptives was greater than two-fold in the former versus the latter. Results
      of logistic regression analysis revealed that the refugee women who had had
      access to subsidized healthcare were significantly more likely to use the
      contraceptive methods with advancing age as compared to the women in the non
      health subsidy group. The difference remained significant after adjusting for
      other variables. CONCLUSIONS/SIGNIFICANCE: Refugee women who are provided
      subsidized healthcare are more inclined to use contraceptives. It is therefore
      important that Afghan refugee women living elsewhere in Pakistan be provided
      healthcare subsidy, whereby their reproductive health indicators could improve
      with reduced fertility. We strongly encourage facilities introducing such
      subsidies to refugees in resource poor settings to assess the impact through
      similar inquiry.

PMID- 23133659
TI  - Standardization of misleading immunoassay based 25-hydroxyvitamin D levels with
      liquid chromatography tandem-mass spectrometry in a large cohort study.
AB  - BACKGROUND: The interest in vitamin D measurement has strongly increased in
      recent years. The best indicator for circulating vitamin D levels is 25-hydroxy
      vitamin D (25(OH)D) which is often measured by different immunoassays. We
      demonstrate problems in comparability of measures by different immunoassays and
      the need for standardization in the context of a large population-based cohort
      study. METHODS: 25(OH)D was measured with the immunoassays Diasorin Liaison in
      2006 in 5,386 women and in the context of another project with IDS-iSYS in 4,199
      men in 2009-2010 (when the Diasorin Liaison was no longer available in the
      version utilized in 2006). Standardization was performed by re-measuring of
      25(OH)D levels in 97 men and 97 women with liquid chromatography tandem-mass
      spectrometry (LC-MS/MS) to obtain linear regression conversion equations.
      RESULTS: Applying a 30 nmol/L cut-off value for vitamin D deficiency would have
      resulted in 48.3% of women and 12.1% of men with vitamin D deficiency ahead of
      standardization. The large gender difference was strongly attenuated after
      standardization of the assays with only 15.7% of women and 14.3% of men with
      vitamin D deficiency. Standardization on average increased the 25(OH)D levels by
      10.3 nmol/L in women and decreased 25(OH)D levels by 2.9 nmol/L in men.
      CONCLUSION: The standardization with LC-MS/MS revealed that much of the observed
      gender difference was only assay-driven and the extremely high proportion of
      48.3% vitamin D deficient women proved to be an exaggeration of the old version
      of the Diasorin-Liaison immunoassay. Standardization of 25(OH)D immunoassay
      results by LC-MS/MS is recommended to improve their accuracy and comparability,
      provided the LC-MS/MS method itself is adequately validated and standardized.

PMID- 23133660
TI  - Patterns of fluctuating asymmetry and shape variation in Chironomus riparius
      (Diptera, Chironomidae) exposed to nonylphenol or lead.
AB  - Deformities and fluctuating asymmetry in chironomid larvae have been proposed as
      sensitive indicators of biological stress and are commonly used to assess the
      ecological impact of human activities. In particular, they have been associated
      in Chironomus riparius, the most commonly used species, with heavy metal and
      pesticide river pollution. In this study, the effect of lead and 4-nonylphenol on
      mouthpart morphological variation of Chironomus riparius larvae was investigated
      by traditional and geometric morphometrics. For this purpose, first to fourth
      instar larvae were exposed to sediment spiked with lead (from 3.0 to 456.9 mg/kg
      dry weight) or 4-NP (from 0.1 to 198.8 mg/kg dry weight). Mentum phenotypic
      response to pollutants was assessed by four parameters: (1) the frequency of
      deformities, (2) fluctuating asymmetry of mentum length, (3) fluctuating
      asymmetry of mentum shape and (4) the mentum mean shape changes. Despite the
      bioaccumulation of pollutants in the chironomid's body, no significant
      differences between control and stressed groups were found for mouthpart
      deformities and fluctuating asymmetry of mentum length. Slight effects on mentum
      shape fluctuating asymmetry were observed for two stressed groups. Significant
      mean shape changes, consisting of tooth size increase and tooth closing, were
      detected for lead and 4-NP exposure respectively. Those variations, however, were
      negligible in comparison to mentum shape changes due to genetic effects. These
      results suggest that the use of mentum variation as an indicator of toxic stress
      in Chironomus riparius should be considered cautiously.

PMID- 23133661
TI  - Endosomal maturation, Rab7 GTPase and phosphoinositides in African swine fever
      virus entry.
AB  - Here we analyzed the dependence of African swine fever virus (ASFV) infection on
      the integrity of the endosomal pathway. Using confocal immunofluorescence with
      antibodies against viral capsid proteins, we found colocalization of incoming
      viral particles with early endosomes (EE) during the first minutes of infection.
      Conversely, viral capsid protein was not detected in acidic late endosomal
      compartments, multivesicular bodies (MVBs), late endosomes (LEs) or lysosomes
      (LY). Using an antibody against a viral inner core protein, we found
      colocalization of viral cores with late compartments from 30 to 60 minutes
      postinfection. The absence of capsid protein staining in LEs and LYs suggested
      that virus desencapsidation would take place at the acid pH of these organelles.
      In fact, inhibitors of intraluminal acidification of endosomes caused retention
      of viral capsid staining virions in Rab7 expressing endosomes and more
      importantly, severely impaired subsequent viral protein production. Endosomal
      acidification in the first hour after virus entry was essential for successful
      infection but not thereafter. In addition, altering the balance of
      phosphoinositides (PIs) which are responsible of the maintenance of the endocytic
      pathway impaired ASFV infection. Early infection steps were dependent on the
      production of phosphatidylinositol 3-phosphate (PtdIns3P) which is involved in EE
      maturation and multivesicular body (MVB) biogenesis and on the interconversion of
      PtdIns3P to phosphatidylinositol 3, 5-biphosphate (PtdIns(3,5)P(2)). Likewise,
      GTPase Rab7 activity should remain intact, as well as processes related to LE
      compartment physiology, which are crucial during early infection. Our data
      demonstrate that the EE and LE compartments and the integrity of the endosomal
      maturation pathway orchestrated by Rab proteins and PIs play a central role
      during early stages of ASFV infection.

PMID- 23133662
TI  - A single kernel-based approach to extract drug-drug interactions from biomedical
      literature.
AB  - When one drug influences the level or activity of another drug this is known as a
      drug-drug interaction (DDI). Knowledge of such interactions is crucial for
      patient safety. However, the volume and content of published biomedical
      literature on drug interactions is expanding rapidly, making it increasingly
      difficult for DDIs database curators to detect and collate DDIs information
      manually. In this paper, we propose a single kernel-based approach to extract
      DDIs from biomedical literature. This novel kernel-based approach can effectively
      make full use of syntactic structural information of the dependency graph. In
      particular, our approach can efficiently represent both single subgraph
      topological information and the relation of two subgraphs in the dependency
      graph. Experimental evaluations showed that our single kernel-based approach can
      achieve state-of-the-art performance on the publicly available DDI corpus without
      exploiting multiple kernels or additional domain resources.

PMID- 23133663
TI  - Dopaminergic neuronal loss and dopamine-dependent locomotor defects in Fbxo7
      deficient zebrafish.
AB  - Recessive mutations in the F-box only protein 7 gene (FBXO7) cause PARK15, a
      mendelian form of early-onset, levodopa-responsive parkinsonism with severe loss
      of nigrostriatal dopaminergic neurons. However, the function of the protein
      encoded by FBXO7, and the pathogenesis of PARK15 remain unknown. No animal models
      of this disease exist. Here, we report the generation of a vertebrate model of
      PARK15 in zebrafish. We first show that the zebrafish Fbxo7 homolog protein
      (zFbxo7) is expressed abundantly in the normal zebrafish brain. Next, we used two
      zFbxo7-specific morpholinos (targeting protein translation and mRNA splicing,
      respectively), to knock down the zFbxo7 expression. The injection of either of
      these zFbxo7-specific morpholinos in the fish embryos induced a marked decrease
      in the zFbxo7 protein expression, and a range of developmental defects.
      Furthermore, whole-mount in situ mRNA hybridization showed abnormal patterning
      and significant decrease in the number of diencephalic tyrosine hydroxylase
      expressing neurons, corresponding to the human nigrostriatal or ventral tegmental
      dopaminergic neurons. Of note, the number of the dopamine transporter-expressing
      neurons was much more severely depleted, suggesting dopaminergic dysfunctions
      earlier and larger than those due to neuronal loss. Last, the zFbxo7 morphants
      displayed severe locomotor disturbances (bradykinesia), which were dramatically
      improved by the dopaminergic agonist apomorphine. The severity of these
      morphological and behavioral abnormalities correlated with the severity of zFbxo7
      protein deficiency. Moreover, the effects of the co-injection of zFbxo7- and p53
      specific morpholinos were similar to those obtained with zFbxo7-specific
      morpholinos alone, supporting further the contention that the observed phenotypes
      were specifically due to the knock down of zFbxo7. In conclusion, this novel
      vertebrate model reproduces pathologic and behavioral hallmarks of human
      parkinsonism (dopaminergic neuronal loss and dopamine-dependent bradykinesia),
      representing therefore a valid tool for investigating the mechanisms of selective
      dopaminergic neuronal death, and screening for modifier genes and therapeutic
      compounds.

PMID- 23133664
TI  - Dasatinib inhibits CXCR4 signaling in chronic lymphocytic leukaemia cells and
      impairs migration towards CXCL12.
AB  - Chemokines and their ligands play a critical role in enabling chronic lymphocytic
      leukaemia (CLL) cells access to protective microenvironmental niches within
      tissues, ultimately resulting in chemoresistance and relapse: disruption of these
      signaling pathways has become a novel therapeutic approach in CLL. The tyrosine
      kinase inhibitor dasatinib inhibits migration of several cell lines from solid
      organ tumours, but effects on CLL cells have not been reported. We studied the
      effect of clinically achievable concentrations of dasatinib on signaling induced
      by the chemokine CXCL12 through its' receptor CXCR4, which is highly expressed on
      CLL cells. Dasatinib pre-treatment inhibited Akt and ERK phosphorylation in CLL
      cells upon stimulation with CXCL12. Dasatinib also significantly diminished the
      rapid increase in actin polymerisation observed in CLL cells following CXCL12
      stimulation. Moreover, the drug significantly inhibited chemotaxis in a transwell
      assay, and reduced the percentage of cells able to migrate beneath a CXCL12
      expressing murine stromal cell line. Dasatinib also abrogated the anti-apoptotic
      effect of prolonged CXCL12 stimulation on cultured CLL cells. These data suggest
      that dasatinib, akin to other small molecule kinase inhibitors targeting the B
      cell receptor signaling pathway, may redistribute CLL cells from protective
      tissue niches to the peripheral blood, and support the investigation of dasatinib
      in combination strategies.

PMID- 23133665
TI  - Phylogeny of the genus Chrysanthemum L.: evidence from single-copy nuclear gene
      and chloroplast DNA sequences.
AB  - Chrysanthemum L. (Asteraceae-Anthemideae) is a genus with rapid speciation. It
      comprises about 40 species, most of which are distributed in East Asia. Many of
      these are narrowly distributed and habitat-specific. Considerable variations in
      morphology and ploidy are found in this genus. Some species have been the
      subjects of many studies, but the relationships between Chrysanthemum and its
      allies and the phylogeny of this genus remain poorly understood. In the present
      study, 32 species/varieties from Chrysanthemum and 11 from the allied genera were
      analyzed using DNA sequences of the single-copy nuclear CDS gene and seven cpDNA
      loci (psbA-trnH, trnC-ycf6, ycf6-psbM, trnY-rpoB, rpS4-trnT, trnL-F, and rpL16).
      The cpDNA and nuclear CDS gene trees both suggest that 1) Chrysanthemum is not a
      monophyletic taxon, and the affinity between Chrysanthemum and Ajania is so close
      that these two genera should be incorporated taxonomically; 2) Phaeostigma is
      more closely related to the Chrysanthemum+Ajania than other generic allies.
      According to pollen morphology and to the present cpDNA and CDS data, Ajania
      purpurea is a member of Phaeostigma. Species differentiation in Chrysanthemum
      appears to be correlated with geographic and environmental conditions. The
      Chinese Chrysanthemum species can be divided into two groups, the C. zawadskii
      group and the C. indicum group. The former is distributed in northern China and
      the latter in southern China. Many polyploid species, such as C. argyrophyllum,
      may have originated from allopolyploidization involving divergent progenitors.
      Considering all the evidence from present and previous studies, we conclude that
      geographic and ecological factors as well as hybridization and polyploidy play
      important roles in the divergence and speciation of the genus Chrysanthemum.

PMID- 23133666
TI  - A longitudinal study of atrophy in amnestic mild cognitive impairment and normal
      aging revealed by cortical thickness.
AB  - In recent years, amnestic mild cognitive impairment (aMCI) has attracted
      significant attention as an indicator of high risk for Alzheimer's disease. An
      understanding of the pathology of aMCI may benefit the development of effective
      clinical treatments for dementia. In this work, we measured the cortical
      thickness of 109 aMCI subjects and 99 normal controls (NC) twice over two years.
      The longitudinal changes and the cross-sectional differences between the two
      types of participants were explored using the vertex thickness values. The
      thickness of the cortex in aMCI was found significantly reduced in both
      longitudinal and between-group comparisons, mainly in the temporal lobe,
      superolateral parietal lobe and some regions of the frontal cortices. Compared to
      NC, the aMCI showed a significantly high atrophy rate in the left lateral
      temporal lobe and left parahippocampal gyrus over two years. Additionally, a
      significant positive correlation between brain atrophy and the decline of Mini
      Mental State Examination (MMSE) scores was also found in the left superior and
      left middle temporal gyrus in aMCI. These findings demonstrated specific
      longitudinal spatial patterns of cortical atrophy in aMCI and NC. The higher
      atrophy rate in aMCI might be responsible for the accelerated functional decline
      in the aMCI progression process.

PMID- 23133667
TI  - Detection of a bocavirus circular genome in fecal specimens from children with
      acute diarrhea in Beijing, China.
AB  - To determine if human bocavirus 2 (HBoV2) has a circular genome similar to the
      head-to-tail sequence of HBoV1 and the episomal form of HBoV3, 15 HBoV2 positive
      samples identified from 553 stool specimens from children with acute diarrhea
      were tested for a head-to-tail sequence using TaqMan-based real-time PCR. A
      circular genome with a head-to-tail sequence was identified in one (BJQ435) out
      of 15 samples tested by nested PCR. The complete circular genome of HBoV2-C1
      (BJQ435) was 5307 nt in length and was flanked with a 520 nt-long terminal non
      coding region (NCR). The secondary structure of HBoV2 -C1 had some differences
      compared to HBoV3-E1 (JN086998). Our study indicates that the HBoV genome exists
      in the form of a head-to-tail monomer and provides more information for
      understanding the HBoV replication mechanism.

PMID- 23133668
TI  - Extension of yeast chronological lifespan by methylamine.
AB  - BACKGROUND: Chronological aging of yeast cells is commonly used as a model for
      aging of human post-mitotic cells. The yeast Saccharomyces cerevisiae grown on
      glucose in the presence of ammonium sulphate is mainly used in yeast aging
      research. We have analyzed chronological aging of the yeast Hansenula polymorpha
      grown at conditions that require primary peroxisome metabolism for growth.
      METHODOLOGY/PRINCIPAL FINDINGS: The chronological lifespan of H. polymorpha is
      strongly enhanced when cells are grown on methanol or ethanol, metabolized by
      peroxisome enzymes, relative to growth on glucose that does not require
      peroxisomes. The short lifespan of H. polymorpha on glucose is mainly due to
      medium acidification, whereas most likely ROS do not play an important role.
      Growth of cells on methanol/methylamine instead of methanol/ammonium sulphate
      resulted in further lifespan enhancement. This was unrelated to medium
      acidification. We show that oxidation of methylamine by peroxisomal amine oxidase
      at carbon starvation conditions is responsible for lifespan extension. The
      methylamine oxidation product formaldehyde is further oxidized resulting in NADH
      generation, which contributes to increased ATP generation and reduction of ROS
      levels in the stationary phase. CONCLUSION/SIGNIFICANCE: We conclude that primary
      peroxisome metabolism enhanced chronological lifespan of H. polymorpha. Moreover,
      the possibility to generate NADH at carbon starvation conditions by an organic
      nitrogen source supports further extension of the lifespan of the cell.
      Consequently, the interpretation of CLS analyses in yeast should include possible
      effects on the energy status of the cell.

PMID- 23133669
TI  - Ion conduction through the hERG potassium channel.
AB  - The inward rectifier voltage-gated potassium channel hERG is of primary
      importance for the regulation of the membrane potential of cardiomyocytes. Unlike
      most voltage-gated K(+)-channels, hERG shows a low elementary conductance at
      physiological voltage and potassium concentration. To investigate the molecular
      features underlying this unusual behavior, we simulated the ion conduction
      through the selectivity filter at a fully atomistic level by means of molecular
      dynamics-based methods, using a homology-derived model. According to our
      calculations, permeation of potassium ions can occur along two pathways, one
      involving site vacancies inside the filter (showing an energy barrier of about 6
      kcal mol(-1)), and the other characterized by the presence of a knock-on
      intermediate (about 8 kcal mol(-1)). These barriers are indeed in accordance with
      a low conductance behavior, and can be explained in terms of a series of
      distinctive structural features displayed by the hERG ion permeation pathway.

PMID- 23133670
TI  - Identification of small molecules that suppress ricin-induced stress-activated
      signaling pathways.
AB  - Ricin is a member of the ribosome-inactivating protein (RIP) family of plant and
      bacterial toxins. In this study we used a high-throughput, cell-based assay to
      screen more than 118,000 compounds from diverse chemical libraries for molecules
      that reduced ricin-induced cell death. We describe three compounds, PW66, PW69,
      and PW72 that at micromolar concentrations significantly delayed ricin-induced
      cell death. None of the compounds had any demonstrable effect on ricin's ability
      to arrest protein synthesis in cells or on ricin's enzymatic activity as assessed
      in vitro. Instead, all three compounds appear to function by blocking downstream
      stress-induced signaling pathways associated with the toxin-mediated apoptosis.
      PW66 virtually eliminated ricin-induced TNF-alpha secretion by J774A.1
      macrophages and concomitantly blocked activation of the p38 MAPK and JNK
      signaling pathways. PW72 suppressed ricin-induced TNF-alpha secretion, but not
      p38 MAPK and JNK signaling. PW69 suppressed activity of the executioner caspases
      3/7 in ricin toxin- and Shiga toxin 2-treated cells. While the actual molecular
      targets of the three compounds have yet to be identified, these data nevertheless
      underscore the potential of small molecules to down-regulate inflammatory
      signaling pathways associated with exposure to the RIP family of toxins.

PMID- 23133671
TI  - Fibroblast growth factor 10-fibroblast growth factor receptor 2b mediated
      signaling is not required for adult glandular stomach homeostasis.
AB  - The signaling pathways that are essential for gastric organogenesis have been
      studied in some detail; however, those that regulate the maintenance of the
      gastric epithelium during adult homeostasis remain unclear. In this study, we
      investigated the role of Fibroblast growth factor 10 (FGF10) and its main
      receptor, Fibroblast growth factor receptor 2b (FGFR2b), in adult glandular
      stomach homeostasis. We first showed that mouse adult glandular stomach expressed
      Fgf10, its receptors, Fgfr1b and Fgfr2b, and most of the other FGFR2b ligands
      (Fgf1, Fgf7, Fgf22) except for Fgf3 and Fgf20. Fgf10 expression was mesenchymal
      whereas FGFR1 and FGFR2 expression were mostly epithelial. Studying double
      transgenic mice that allow inducible overexpression of Fgf10 in adult mice, we
      showed that Fgf10 overexpression in normal adult glandular stomach increased
      epithelial proliferation, drove mucous neck cell differentiation, and reduced
      parietal and chief cell differentiation. Although a similar phenotype can be
      associated with the development of metaplasia, we found that Fgf10 overexpression
      for a short duration does not cause metaplasia. Finally, investigating double
      transgenic mice that allow the expression of a soluble form of Fgfr2b, FGF10's
      main receptor, which acts as a dominant negative, we found no significant changes
      in gastric epithelial proliferation or differentiation in the mutants. Our work
      provides evidence, for the first time, that the FGF10-FGFR2b signaling pathway is
      not required for epithelial proliferation and differentiation during adult
      glandular stomach homeostasis.

PMID- 23133672
TI  - Natural killer cells are characterized by the concomitantly increased interferon
      gamma and cytotoxicity in acute resolved hepatitis B patients.
AB  - Natural killer (NK) cells are abundant in the liver and have been implicated in
      inducing hepatocellular damage in patients with chronic hepatitis B virus (HBV)
      infection. However, the role of NK cells in acute HBV infection remains to be
      elucidated. We comprehensively characterized NK cells and investigated their
      roles in HBV clearance and liver pathology in 19 chronic hepatitis B (CHB)
      patients and 21 acute hepatitis B (AHB) patients as well as 16 healthy subjects.
      It was found that NKp46(+) NK cells were enriched in the livers of AHB and CHB
      patients. We further found that peripheral NK cells from AHB patients expressed
      higher levels of activation receptors and lower levels of inhibitory receptors
      than those from CHB patients and HC subjects, thus displaying the increased
      cytolytic activity and interferon-gamma production. NK cell activation levels
      were also correlated positively with serum alanine aminotransferase levels and
      negatively with plasma HBV DNA levels in AHB patients, which is further confirmed
      by the longitudinal follow-up of AHB patients. Serum pro-inflammatory cytokine
      and chemokine levels were also increased in AHB patients as compared with CHB and
      HC subjects. Thus, the concomitantly increased interferon-gamma and cytotoxicity
      of NK cells were associated with liver injury and viral clearance in AHB
      patients.

PMID- 23133673
TI  - The single T65S mutation generates brighter cyan fluorescent proteins with
      increased photostability and pH insensitivity.
AB  - Cyan fluorescent proteins (CFP) derived from Aequorea victoria GFP, carrying a
      tryptophan-based chromophore, are widely used as FRET donors in live cell
      fluorescence imaging experiments. Recently, several CFP variants with near
      ultimate photophysical performances were obtained through a mix of site-directed
      and large scale random mutagenesis. To understand the structural bases of these
      improvements, we have studied more specifically the consequences of the single
      site T65S mutation. We find that all CFP variants carrying the T65S mutation not
      only display an increased fluorescence quantum yield and a simpler fluorescence
      emission decay, but also show an improved pH stability and strongly reduced
      reversible photoswitching reactions. Most prominently, the Cerulean-T65S variant
      reaches performances nearly equivalent to those of mTurquoise, with QY  = 0.84,
      an almost pure single exponential fluorescence decay and an outstanding stability
      in the acid pH range (pK(1/2) = 3.6). From the detailed examination of
      crystallographic structures of different CFPs and GFPs, we conclude that these
      improvements stem from a shift in the thermodynamic balance between two well
      defined configurations of the residue 65 hydroxyl. These two configurations
      differ in their relative stabilization of a rigid chromophore, as well as in
      relaying the effects of Glu222 protonation at acid pHs. Our results suggest a
      simple method to greatly improve numerous FRET reporters used in cell imaging,
      and bring novel insights into the general structure-photophysics relationships of
      fluorescent proteins.

PMID- 23133674
TI  - Identification of the functional domains of the telomere protein Rap1 in
      Schizosaccharomyces pombe.
AB  - The telomere at the end of a linear chromosome plays crucial roles in genome
      stability. In the fission yeast Schizosaccharomyces pombe, the Rap1 protein, one
      of the central players at the telomeres, associates with multiple proteins to
      regulate various telomere functions, such as the maintenance of telomere DNA
      length, telomere end protection, maintenance of telomere heterochromatin, and
      telomere clustering in meiosis. The molecular bases of the interactions between
      Rap1 and its partners, however, remain largely unknown. Here, we describe the
      identification of the interaction domains of Rap1 with its partners. The
      Bqt1/Bqt2 complex, which is required for normal meiotic progression, Poz1, which
      is required for telomere length control, and Taz1, which is required for the
      recruitment of Rap1 to telomeres, bind to distinct domains in the C-terminal half
      of Rap1. Intriguingly, analyses of a series of deletion mutants for rap1(+) have
      revealed that the long N-terminal region (1-456 a.a. [amino acids]) of Rap1 (full
      length: 693 a.a.) is not required for telomere DNA length control, telomere end
      protection, and telomere gene silencing, whereas the C-terminal region (457-693
      a.a.) containing Poz1- and Taz1-binding domains plays important roles in those
      functions. Furthermore, the Bqt1/Bqt2- and Taz1-binding domains are essential for
      normal spore formation after meiosis. Our results suggest that the C-terminal
      half of Rap1 is critical for the primary telomere functions, whereas the N
      terminal region containing the BRCT (BRCA1 C-terminus) and Myb domains, which are
      evolutionally conserved among the Rap1 family proteins, does not play a major
      role at the telomeres.

PMID- 23133675
TI  - GLP-1 receptor activation inhibits VLDL production and reverses hepatic steatosis
      by decreasing hepatic lipogenesis in high-fat-fed APOE*3-Leiden mice.
AB  - OBJECTIVE: In addition to improve glucose intolerance, recent studies suggest
      that glucagon-like peptide-1 (GLP-1) receptor agonism also decreases triglyceride
      (TG) levels. The aim of this study was to evaluate the effect of GLP-1 receptor
      agonism on very-low-density lipoprotein (VLDL)-TG production and liver TG
      metabolism. EXPERIMENTAL APPROACH: The GLP-1 peptide analogues CNTO3649 and
      exendin-4 were continuously administered subcutaneously to high fat diet-fed
      APOE*3-Leiden transgenic mice. After 4 weeks, hepatic VLDL production, lipid
      content, and expression profiles of selected genes involved in lipid metabolism
      were determined. RESULTS: CNTO3649 and exendin-4 reduced fasting plasma glucose
      (up to -30% and -28% respectively) and insulin (-43% and -65% respectively). In
      addition, these agents reduced VLDL-TG production (-36% and -54% respectively)
      and VLDL-apoB production (-36% and -43% respectively), indicating reduced
      production of VLDL particles rather than reduced lipidation of apoB. Moreover,
      they markedly decreased hepatic content of TG (-39% and -55% respectively),
      cholesterol (-30% and -55% respectively), and phospholipids (-23% and -36%
      respectively), accompanied by down-regulation of expression of genes involved in
      hepatic lipogenesis (Srebp-1c, Fasn, Dgat1) and apoB synthesis (Apob).
      CONCLUSION: GLP-1 receptor agonism reduces VLDL production and hepatic steatosis
      in addition to an improvement of glycemic control. These data suggest that GLP
      receptor agonists could reduce hepatic steatosis and ameliorate dyslipidemia in
      patients with type 2 diabetes mellitus.

PMID- 23133676
TI  - Total beta-adrenoceptor knockout slows conduction and reduces inducible
      arrhythmias in the mouse heart.
AB  - INTRODUCTION: Beta-adrenoceptors (beta-AR) play an important role in the
      neurohumoral regulation of cardiac function. Three beta-AR subtypes (beta(1),
      beta(2), beta(3)) have been described so far. Total deficiency of these
      adrenoceptors (TKO) results in cardiac hypotrophy and negative inotropy. TKO
      represents a unique mouse model mimicking total unselective medical beta-blocker
      therapy in men. Electrophysiological characteristics of TKO have not yet been
      investigated in an animal model. METHODS: In vivo electrophysiological studies
      using right heart catheterisation were performed in 10 TKO mice and 10 129SV wild
      type control mice (WT) at the age of 15 weeks. Standard surface ECG, intracardiac
      and electrophysiological parameters, and arrhythmia inducibility were analyzed.
      RESULTS: The surface ECG of TKO mice revealed a reduced heart rate (359.2+/-20.9
      bpm vs. 461.1+/-33.3 bpm; p<0.001), prolonged P wave (17.5+/-3.0 ms vs. 15.1+/
      1.2 ms; p = 0.019) and PQ time (40.8+/-2.4 ms vs. 37.3+/-3.0 ms; p = 0.013)
      compared to WT. Intracardiac ECG showed a significantly prolonged infra-Hisian
      conductance (HV-interval: 12.9+/-1.4 ms vs. 6.8+/-1.0 ms; p<0.001). Functional
      testing showed prolonged atrial and ventricular refractory periods in TKO (40.5+/
      15.5 ms vs. 21.3+/-5.8 ms; p = 0.004; and 41.0+/-9.7 ms vs. 28.3+/-6.6 ms; p =
      0.004, respectively). In TKO both the probability of induction of atrial
      fibrillation (12% vs. 24%; p<0.001) and of ventricular tachycardias (0% vs. 26%;
      p<0.001) were significantly reduced. CONCLUSION: TKO results in significant
      prolongations of cardiac conduction times and refractory periods. This was
      accompanied by a highly significant reduction of atrial and ventricular
      arrhythmias. Our finding confirms the importance of beta-AR in arrhythmogenesis
      and the potential role of unspecific beta-receptor-blockade as therapeutic
      target.

PMID- 23133677
TI  - The evolutionary pattern of glycosylation sites in influenza virus (H5N1)
      hemagglutinin and neuraminidase.
AB  - Two glycoproteins, hemagglutinin (HA) and neuraminidase (NA), on the surface of
      influenza viruses play crucial roles in transfaunation, membrane fusion and the
      release of progeny virions. To explore the distribution of N-glycosylation sites
      (glycosites) in these two glycoproteins, we collected and aligned the amino acid
      sequences of all the HA and NA subtypes. Two glycosites were located at HA0
      cleavage sites and fusion peptides and were strikingly conserved in all HA
      subtypes, while the remaining glycosites were unique to their subtypes. Two to
      four conserved glycosites were found in the stalk domain of NA, but these are
      affected by the deletion of specific stalk domain sequences. Another highly
      conserved glycosite appeared at the top center of tetrameric global domain, while
      the others glycosites were distributed around the global domain. Here we present
      a detailed investigation of the distribution and the evolutionary pattern of the
      glycosites in the envelope glycoproteins of IVs, and further focus on the H5N1
      virus and conclude that the glycosites in H5N1 have become more complicated in HA
      and less influential in NA in the last five years.

PMID- 23133678
TI  - Chronic intrinsic transient tracheal occlusion elicits diaphragmatic muscle fiber
      remodeling in conscious rodents.
AB  - BACKGROUND: Although the prevalence of inspiratory muscle strength training has
      increased in clinical medicine, its effect on diaphragm fiber remodeling is not
      well-understood and no relevant animal respiratory muscle strength training
      rehabilitation experimental models exist. We tested the postulate that intrinsic
      transient tracheal occlusion (ITTO) conditioning in conscious animals would
      provide a novel experimental model of respiratory muscle strength training, and
      used significant increases in diaphragmatic fiber cross-sectional area (CSA) as
      the primary outcome measure. We hypothesized that ITTO would increase costal
      diaphragm fiber CSA and further hypothesized a greater duration and magnitude of
      occlusions would amplify remodeling. METHODOLOGY/PRINCIPAL FINDINGS: Sprague
      Dawley rats underwent surgical placement of a tracheal cuff and were randomly
      assigned to receive daily either 10-minute sessions of ITTO, extended-duration,
      20-minute ITTO (ITTO-20), partial obstruction with 50% of cuff inflation pressure
      (ITTO-PAR) or observation (SHAM) over two weeks. After the interventions, fiber
      morphology, myosin heavy chain composition and CSA were examined in the crural
      and ventral, medial, and dorsal costal regions. In the medial costal diaphragm,
      with ITTO, type IIx/b fibers were 26% larger in the medial costal diaphragm
      (p<0.01) and 24% larger in the crural diaphragm (p<0.05). No significant changes
      in fiber composition or morphology were detected. ITTO-20 sessions also yielded
      significant increases in medial costal fiber cross-sectional area, but the
      effects were not greater than those elicited by 10-minute sessions. On the other
      hand, ITTO-PAR resulted in partial airway obstruction and did not generate fiber
      hypertrophy. CONCLUSIONS/SIGNIFICANCE: The results suggest that the magnitude of
      the load was more influential in altering fiber cross-sectional area than
      extended-duration conditioning sessions. The results also indicated that ITTO was
      associated with type II fiber hypertrophy in the medial costal region of the
      diaphragm and may be an advantageous experimental model of clinical respiratory
      muscle strength training.

PMID- 23133679
TI  - The role of carrion supply in the abundance of deep-water fish off California.
AB  - Few time series of deep-sea systems exist from which the factors affecting
      abyssal fish populations can be evaluated. Previous analysis showed an increase
      in grenadier abundance, in the eastern North Pacific, which lagged epibenthic
      megafaunal abundance, mostly echinoderms, by 9-20 months. Subsequent diet studies
      suggested that carrion is the grenadier's most important food. Our goal was to
      evaluate if changes in carrion supply might drive the temporal changes in
      grenadier abundance. We analyzed a unique 17 year time series of abyssal
      grenadier abundance and size, collected at Station M (4100 m, 220 km offshore of
      Pt. Conception, California), and reaffirmed the increase in abundance and also
      showed an increase in mean size resulting in a ~6 fold change in grenadier
      biomass. We compared this data with abundance estimates for surface living nekton
      (pacific hake and jack mackerel) eaten by the grenadiers as carrion. A
      significant positive correlation between Pacific hake (but not jack mackerel) and
      grenadiers was found. Hake seasonally migrate to the waters offshore of
      California to spawn. They are the most abundant nekton species in the region and
      the target of the largest commercial fishery off the west coast. The correlation
      to grenadier abundance was strongest when using hake abundance metrics from the
      area within 100 nmi of Station M. No significant correlation between grenadier
      abundance and hake biomass for the entire California current region was found.
      Given the results and grenadier longevity, migration is likely responsible for
      the results and the location of hake spawning probably is more important than the
      size of the spawning stock in understanding the dynamics of abyssal grenadier
      populations. Our results suggest that some abyssal fishes' population dynamics
      are controlled by the flux of large particles of carrion. Climate and fishing
      pressures affecting epipelagic fish stocks could readily modulate deep-sea fish
      dynamics.

PMID- 23133680
TI  - LINE-1 retroelements complexed and inhibited by activation induced cytidine
      deaminase.
AB  - LINE-1 (abbreviated L1) is a major class of retroelements in humans and mice. If
      unrestricted, retroelements accumulate in the cytoplasm and insert their DNA into
      the host genome, with the potential to cause autoimmune disease and cancer.
      Retroviruses and other retroelements are inhibited by proteins of the APOBEC
      family, of which activation-induced cytidine deaminase (AID) is a member.
      Although AID is mainly known for being a DNA mutator shaping the antibody
      repertoire in B lymphocytes, we found that AID also restricts de novo L1
      integrations in B- and non-B-cell lines. It does so by decreasing the protein
      level of open reading frame 1 (ORF1) of both exogenous and endogenous L1. In
      activated B lymphocytes, AID deficiency increased L1 mRNA 1.6-fold and murine
      leukemia virus (MLV) mRNA 2.7-fold. In cell lines and activated B lymphocytes,
      AID forms cytoplasmic high-molecular-mass complexes with L1 mRNA, which may
      contribute to L1 restriction. Because AID-deficient activated B lymphocytes do
      not express ORF1 protein, we suggest that ORF1 protein expression is inhibited by
      additional restriction factors in these cells. The greater increase in MLV
      compared to L1 mRNA in AID-deficient activated B lymphocytes may indicate less
      strict surveillance of retrovirus.

PMID- 23133681
TI  - Human beta-defensin 3 is up-regulated in cutaneous leprosy type 1 reactions.
AB  - BACKGROUND: Leprosy, a chronic granulomatous disease affecting the skin and
      nerves, is caused by Mycobacterium leprae (M. leprae). The type of leprosy
      developed depends upon the host immune response. Type 1 reactions (T1Rs), that
      complicate borderline and lepromatous leprosy, are due to an increase in cell
      mediated immunity and manifest as nerve damage and skin inflammation. Owing to
      the increase in inflammation in the skin of patients with T1Rs, we sought to
      investigate the activation of the innate immune system during reactionary events.
      Specifically, we investigated the expression levels of human beta-defensins
      (hBDs) 2 and 3 in the skin of patients with T1Rs, in keratinocytes, and in
      macrophages stimulated with M. leprae and corticosteroids. RESULTS: Skin biopsies
      from twenty-three patients with Type 1 reactions were found to have higher
      transcript levels of hBD3 as compared to fifteen leprosy patients without Type 1
      reactions, as measured by qPCR. Moreover, we observed that keratinocytes but not
      macrophages up-regulated hBD2 and hBD3 in response to M. leprae stimulation in
      vitro. Corticosteroid treatment of patients with T1Rs caused a suppression of
      hBD2 and hBD3 in skin biopsies, as measured by qPCR. In vitro, corticosteroids
      suppressed M. leprae-dependent induction of hBD2 and hBD3 in keratinocytes.
      CONCLUSIONS: This study demonstrates that hBD3 is induced in leprosy Type 1
      Reactions and suppressed by corticosteroids. Furthermore, our findings
      demonstrate that keratinocytes are responsive to M. leprae and lend support for
      additional studies on keratinocyte innate immunity in leprosy and T1Rs. TRIAL
      REGISTRATION: Controlled-Trials.com ISRCTN31894035.

PMID- 23133682
TI  - Fexinidazole: a potential new drug candidate for Chagas disease.
AB  - BACKGROUND: New safe and effective treatments for Chagas disease (CD) are
      urgently needed. Current chemotherapy options for CD have significant
      limitations, including failure to uniformly achieve parasitological cure or
      prevent the chronic phase of CD, and safety and tolerability concerns.
      Fexinidazole, a 2-subsituted 5-nitroimidazole drug candidate rediscovered
      following extensive compound mining by the Drugs for Neglected Diseases
      initiative and currently in Phase I clinical study for the treatment of human
      African trypanosomiasis, was evaluated in experimental models of acute and
      chronic CD caused by different strains of Trypanosoma cruzi. METHODS AND
      FINDINGS: We investigated the in vivo activity of fexinidazole against T. cruzi,
      using mice as hosts. The T. cruzi strains used in the study were previously
      characterized in murine models as susceptible (CL strain), partially resistant (Y
      strain), and resistant (Colombian and VL-10 strains) to the drugs currently in
      clinical use, benznidazole and nifurtimox. Our results demonstrated that
      fexinidazole was effective in suppressing parasitemia and preventing death in
      infected animals for all strains tested. In addition, assessment of definitive
      parasite clearance (cure) through parasitological, PCR, and serological methods
      showed cure rates of 80.0% against CL and Y strains, 88.9% against VL-10 strain,
      and 77.8% against Colombian strain among animals treated during acute phase, and
      70% (VL-10 strain) in those treated in chronic phase. Benznidazole had a similar
      effect against susceptible and partially resistant T. cruzi strains. Fexinidazole
      treatment was also shown to reduce myocarditis in all animals infected with VL-10
      or Colombian resistant T. cruzi strains, although parasite eradication was not
      achieved in all treated animals at the tested doses. CONCLUSIONS: Fexinidazole is
      an effective oral treatment of acute and chronic experimental CD caused by
      benznidazole-susceptible, partially resistant, and resistant T. cruzi. These
      findings illustrate the potential of fexinidazole as a drug candidate for the
      treatment of human CD.

PMID- 23133683
TI  - Burden of visceral leishmaniasis in villages of eastern Gedaref State, Sudan: an
      exhaustive cross-sectional survey.
AB  - BACKGROUND: Since December 2009, Medecins Sans Frontieres has diagnosed and
      treated patients with visceral leishmaniasis (VL) in Tabarak Allah Hospital,
      eastern Gedaref State, one of the main endemic foci of VL in Sudan. A survey was
      conducted to estimate the VL incidence in villages around Tabarak Allah. METHODS:
      Between the 5(th) of May and the 17(th) of June 2011, we conducted an exhaustive
      door-to-door survey in 45 villages of Al-Gureisha locality. Deaths were
      investigated by verbal autopsies. All individuals with (i) fever of at least two
      weeks, (ii) VL diagnosed and treated in the previous year, and (iii) clinical
      suspicion of post-kala-azar dermal leishmaniasis (PKDL) were referred to medical
      teams for case ascertainment. A new case of VL was a clinical suspect with a
      positive rk39 rapid test or direct agglutination test (DAT). RESULTS: In the 45
      villages screened, 17,702 households were interviewed, for a population of 94,369
      inhabitants. The crude mortality rate over the mean recall period of 409 days was
      0.13/10'000 people per day. VL was a possible or probable cause for 19% of all
      deaths. The VL-specific mortality rate was estimated at 0.9/1000 per year. The
      medical teams examined 551 individuals referred for a history of fever of at
      least two weeks. Out of these, 16 were diagnosed with primary VL. The overall
      incidence of VL over the past year was 7.0/1000 persons per year, or 7.9/1000 per
      year when deaths possibly or probably due to VL were included. Overall, 12.5%
      (11,943/95,609) of the population reported a past VL treatment episode.
      DISCUSSION AND CONCLUSION: VL represents a significant health burden in eastern
      Gedaref State. Active VL case detection had a very low yield in this specific
      setting with adequate access to care and may not be the priority intervention to
      enhance control in similar contexts.

PMID- 23133684
TI  - CT694 and pgp3 as serological tools for monitoring trachoma programs.
AB  - BACKGROUND: Defining endpoints for trachoma programs can be a challenge as
      clinical signs of infection may persist in the absence of detectable bacteria.
      Antibody-based tests may provide an alternative testing strategy for surveillance
      during terminal phases of the program. Antibody-based assays, in particular
      ELISAs, have been shown to be useful to document C. trachomatis genital
      infections, but have not been explored extensively for ocular C. trachomatis
      infections. METHODOLOGY/PRINCIPAL FINDINGS: An antibody-based multiplex assay was
      used to test two C. trachomatis antigens, pgp3 and CT694, for detection of
      trachoma antibodies in bloodspots from Tanzanian children (n = 160) collected
      after multiple rounds of mass azithromycin treatment. Using samples from C.
      trachomatis-positive (by PCR) children from Tanzania (n = 11) and control sera
      from a non-endemic group of U.S. children (n = 122), IgG responses to both pgp3
      and CT694 were determined to be 91% sensitive and 98% specific. Antibody
      responses of Tanzanian children were analyzed with regard to clinical trachoma,
      PCR positivity, and age. In general, children with more intense ocular pathology
      (TF/TI = 2 or most severe) had a higher median antibody response to pgp3 (p =
      0.0041) and CT694 (p = 0.0282) than those with normal exams (TF/TI = 0). However,
      44% of children with no ocular pathology tested positive for antibody, suggesting
      prior infection. The median titer of antibody responses for children less than
      three years of age was significantly lower than those of older children.
      (p<0.0001 for both antigens). CONCLUSIONS/SIGNIFICANCE: The antibody-based
      multiplex assay is a sensitive and specific additional tool for evaluating
      trachoma transmission. The assay can also be expanded to include antigens
      representing different diseases, allowing for a robust assay for monitoring
      across NTD programs.

PMID- 23133685
TI  - Venezuelan equine encephalitis virus activity in the Gulf Coast region of Mexico,
      2003-2010.
AB  - Venezuelan equine encephalitis virus (VEEV) has been the causative agent for
      sporadic epidemics and equine epizootics throughout the Americas since the 1930s.
      In 1969, an outbreak of Venezuelan equine encephalitis (VEE) spread rapidly from
      Guatemala and through the Gulf Coast region of Mexico, reaching Texas in 1971.
      Since this outbreak, there have been very few studies to determine the northward
      extent of endemic VEEV in this region. This study reports the findings of
      serologic surveillance in the Gulf Coast region of Mexico from 2003-2010.
      Phylogenetic analysis was also performed on viral isolates from this region to
      determine whether there have been substantial genetic changes in VEEV since the
      1960s. Based on the findings of this study, the Gulf Coast lineage of subtype IE
      VEEV continues to actively circulate in this region of Mexico and appears to be
      responsible for infection of humans and animals throughout this region, including
      the northern State of Tamaulipas, which borders Texas.

PMID- 23133686
TI  - Accuracy of a dual path platform (DPP) assay for the rapid point-of-care
      diagnosis of human leptospirosis.
AB  - BACKGROUND: Diagnosis of leptospirosis by the gold standard serologic assay, the
      microscopic agglutination test (MAT), requires paired sera and is not widely
      available. We developed a rapid assay using immunodominant Leptospira
      immunoglobulin-like (Lig) proteins in a Dual Path Platform (DPP). This study
      aimed to evaluate the assay's diagnostic performance in the setting of urban
      transmission. METHODOLOGY: We determined test sensitivity using 446 acute and
      convalescent sera from MAT-confirmed case-patients with severe or mild
      leptospirosis in Brazil. We assessed test specificity using 677 sera from the
      following groups: healthy residents of a Brazilian slum with endemic
      transmission, febrile outpatients from the same slum, healthy blood donors, and
      patients with dengue, hepatitis A, and syphilis. Three operators independently
      interpreted visual results without knowing specimen status. RESULTS: The overall
      sensitivity for paired sera was 100% and 73% for severe and mild disease,
      respectively. In the acute phase, the assay achieved a sensitivity of 85% and 64%
      for severe and mild leptospirosis, respectively. Within seven days of illness
      onset, the assay achieved a sensitivity of 77% for severe disease and 60% for
      mild leptospirosis. Sensitivity of the DPP assay was similar to that for IgM
      ELISA and increased with both duration of symptoms (chi-square regression P =
      0.002) and agglutinating titer (Spearman rho = 0.24, P<0.001). Specificity was
      >=93% for dengue, hepatitis A, syphilis, febrile outpatients, and blood donors,
      while it was 86% for healthy slum residents. Inter-operator agreement ranged from
      very good to excellent (kappa: 0.82-0.94) and test-to-test reproducibility was
      also high (kappa: 0.89). CONCLUSIONS: The DPP assay performed acceptably well for
      diagnosis of severe acute clinical leptospirosis and can be easily implemented in
      hospitals and health posts where leptospirosis is a major public health problem.
      However, test accuracy may need improvement for mild disease and early stage
      leptospirosis, particularly in regions with high transmission.

PMID- 23133687
TI  - Sheep skin odor improves trap captures of mosquito vectors of Rift Valley fever.
AB  - In recent years, the East African region has seen an increase in arboviral
      diseases transmitted by blood-feeding arthropods. Effective surveillance to
      monitor and reduce incidence of these infections requires the use of appropriate
      vector sampling tools. Here, trapped skin volatiles on fur from sheep, a known
      preferred host of mosquito vectors of Rift Valley fever virus (RVFV), were used
      with a standard CDC light trap to improve catches of mosquito vectors. We tested
      the standard CDC light trap alone (L), and baited with (a) CO(2) (LC), (b) animal
      volatiles (LF), and (c) CO(2) plus animal volatiles (LCF) in two highly endemic
      areas for RVF in Kenya (Marigat and Ijara districts) from March-June and
      September-December 2010. The incidence rate ratios (IRR) that mosquito species
      chose traps baited with treatments (LCF, LC and LF) instead of the control (L)
      were estimated. Marigat was dominated by secondary vectors and host-seeking
      mosquitoes were 3-4 times more likely to enter LC and LCF traps [IRR = 3.1 and
      IRR = 3.8 respectively] than the L only trap. The LCF trap captured a greater
      number of mosquitoes than the LC trap (IRR = 1.23) although the difference was
      not significant. Analogous results were observed at Ijara, where species were
      dominated by key primary and primary RVFV vectors, with 1.6-, 6.5-, and 8.5-fold
      increases in trap captures recorded in LF, LC and LCF baited traps respectively,
      relative to the control. These catches all differed significantly from those
      trapped in L only. Further, there was a significant increase in trap captures in
      LCF compared to LC (IRR = 1.63). Mosquito species composition and trap counts
      differed between the RVF sites. However, within each site, catches differed in
      abundance only and no species preferences were noted in the different baited
      traps. Identifying the attractive components present in these natural odors
      should lead to development of an effective odor-bait trapping system for
      population density-monitoring and result in improved RVF surveillance especially
      during the inter-epidemic period.

PMID- 23133688
TI  - Relative neurotoxicity of ivermectin and moxidectin in Mdr1ab (-/-) mice and
      effects on mammalian GABA(A) channel activity.
AB  - The anthelmintics ivermectin (IVM) and moxidectin (MOX) display differences in
      toxicity in several host species. Entrance into the brain is restricted by the P
      glycoprotein (P-gp) efflux transporter, while toxicity is mediated through the
      brain GABA(A) receptors. This study compared the toxicity of IVM and MOX in vivo
      and their interaction with GABA(A) receptors in vitro. Drug toxicity was assessed
      in Mdr1ab(-/-) mice P-gp-deficient after subcutaneous administration of
      increasing doses (0.11-2.0 and 0.23-12.9 umol/kg for IVM and MOX in P-gp
      deficient mice and half lethal doses (LD(50)) in wild-type mice). Survival was
      evaluated over 14-days. In Mdr1ab(-/-) mice, LD(50) was 0.46 and 2.3 umol/kg for
      IVM and MOX, respectively, demonstrating that MOX was less toxic than IVM. In P
      gp-deficient mice, MOX had a lower brain-to-plasma concentration ratio and
      entered into the brain more slowly than IVM. The brain sublethal drug
      concentrations determined after administration of doses close to LD(50) were, in
      Mdr1ab(-/-) and wild-type mice, respectively, 270 and 210 pmol/g for IVM and 830
      and 740-1380 pmol/g for MOX, indicating that higher brain concentrations are
      required for MOX toxicity than IVM. In rat alpha1beta2gamma2 GABA channels
      expressed in Xenopus oocytes, IVM and MOX were both allosteric activators of the
      GABA-induced response. The Hill coefficient was 1.52+/-0.45 for IVM and 0.34+/
      0.56 for MOX (p<0.001), while the maximum potentiation caused by IVM and MOX
      relative to GABA alone was 413.7+/-66.1 and 257.4+/-40.6%, respectively (p<0.05),
      showing that IVM causes a greater potentiation of GABA action on this receptor.
      Differences in the accumulation of IVM and MOX in the brain and in the
      interaction of IVM and MOX with GABA(A) receptors account for differences in
      neurotoxicity seen in intact and Mdr1-deficient animals. These differences in
      neurotoxicity of IVM and MOX are important in considering their use in humans.

PMID- 23133689
TI  - Toxocara seropositivity, atopy and wheezing in children living in poor
      neighbourhoods in urban Latin American.
AB  - BACKGROUND: Toxocara canis and T. cati are parasites of dogs and cats,
      respectively, that infect humans and cause human toxocariasis. Infection may
      cause asthma-like symptoms but is often asymptomatic and is associated with a
      marked eosinophilia. Previous epidemiological studies indicate that T. canis
      infection may be associated with the development of atopy and asthma. OBJECTIVES:
      To investigate possible associations between Toxocara spp. seropositivity and
      atopy and childhood wheezing in a population of children living in non-affluent
      areas of a large Latin American city. METHODS: The study was conducted in the
      city of Salvador, Brazil. Data on wheezing symptoms were collected by
      questionnaire, and atopy was measured by the presence of aeroallergen-specific
      IgE (sIgE). Skin prick test (SPT), total IgE and peripheral eosinophilia were
      measured. Toxocara seropositivity was determined by the presence of anti-Toxocara
      IgG antibodies, and intestinal helminth infections were determined by stool
      microscopy. FINDINGS: Children aged 4 to 11 years were studied, of whom 47% were
      seropositive for anti-Toxocara IgG; eosinophilia >4% occurred in 74.2% and >10%
      in 25.4%; 59.6% had elevated levels of total IgE; 36.8% had sIgE>=0.70 kU/L and
      30.4% had SPT for at least one aeroallergen; 22.4% had current wheezing symptoms.
      Anti-Toxocara IgG was positively associated with elevated eosinophils counts,
      total IgE and the presence of specific IgE to aeroallergens but was inversely
      associated with skin prick test reactivity. CONCLUSION: The prevalence of
      Toxocara seropositivity was high in the studied population of children living in
      conditions of poverty in urban Brazil. Toxocara infection, although associated
      with total IgE, sIgE and eosinophilia, may prevent the development of skin
      hypersensitivity to aeroallergens, possibly through increased polyclonal IgE and
      the induction of a modified Th2 immune reaction.

PMID- 23133690
TI  - New insights on taxonomy, phylogeny and population genetics of Leishmania
      (Viannia) parasites based on multilocus sequence analysis.
AB  - The Leishmania genus comprises up to 35 species, some with status still under
      discussion. The multilocus sequence typing (MLST)--extensively used for bacteria-
      has been proposed for pathogenic trypanosomatids. For Leishmania, however, a
      detailed analysis and revision on the taxonomy is still required. We have
      partially sequenced four housekeeping genes--glucose-6-phosphate dehydrogenase
      (G6PD), 6-phosphogluconate dehydrogenase (6PGD), mannose phosphate isomerase
      (MPI) and isocitrate dehydrogenase (ICD)--from 96 Leishmania (Viannia) strains
      and assessed their discriminatory typing capacity. The fragments had different
      degrees of diversity, and are thus suitable to be used in combination for intra-
      and inter-specific inferences. Species-specific single nucleotide polymorphisms
      were detected, but not for all species; ambiguous sites indicating heterozygosis
      were observed, as well as the putative homozygous donor. A large number of
      haplotypes were detected for each marker; for 6PGD a possible ancestral allele
      for L. (Viannia) was found. Maximum parsimony-based haplotype networks were
      built. Strains of different species, as identified by multilocus enzyme
      electrophoresis (MLEE), formed separated clusters in each network, with
      exceptions. NeighborNet of concatenated sequences confirmed species-specific
      clusters, suggesting recombination occurring in L. braziliensis and L.
      guyanensis. Phylogenetic analysis indicates L. lainsoni and L. naiffi as the most
      divergent species and does not support L. shawi as a distinct species, placing it
      in the L. guyanensis cluster. BURST analysis resulted in six clonal complexes
      (CC), corresponding to distinct species. The L. braziliensis strains evaluated
      correspond to one widely geographically distributed CC and another restricted to
      one endemic area. This study demonstrates the value of systematic multilocus
      sequence analysis (MLSA) for determining intra- and inter-species relationships
      and presents an approach to validate the species status of some entities.
      Furthermore, it contributes to the phylogeny of L. (Viannia) and might be helpful
      for epidemiological and population genetics analysis based on haplotype/diplotype
      determinations and inferences.

PMID- 23133691
TI  - Interactions and potential implications of Plasmodium falciparum-hookworm
      coinfection in different age groups in south-central Cote d'Ivoire.
AB  - BACKGROUND: Given the widespread distribution of Plasmodium and helminth
      infections, and similarities of ecological requirements for disease transmission,
      coinfection is a common phenomenon in sub-Saharan Africa and elsewhere in the
      tropics. Interactions of Plasmodium falciparum and soil-transmitted helminths,
      including immunological responses and clinical outcomes of the host, need further
      scientific inquiry. Understanding the complex interactions between these
      parasitic infections is of public health relevance considering that control
      measures targeting malaria and helminthiases are going to scale. METHODOLOGY: A
      cross-sectional survey was carried out in April 2010 in infants, young school
      aged children, and young non-pregnant women in south-central Cote d'Ivoire.
      Stool, urine, and blood samples were collected and subjected to standardized,
      quality-controlled methods. Soil-transmitted helminth infections were identified
      and quantified in stool. Finger-prick blood samples were used to determine
      Plasmodium spp. infection, parasitemia, and hemoglobin concentrations. Iron,
      vitamin A, riboflavin, and inflammation status were measured in venous blood
      samples. PRINCIPAL FINDINGS: Multivariate regression analysis revealed specific
      association between infection and demographic, socioeconomic, host inflammatory
      and nutritional factors. Non-pregnant women infected with P. falciparum had
      significantly lower odds of hookworm infection, whilst a significant positive
      association was found between both parasitic infections in 6- to 8-year-old
      children. Coinfected children had lower odds of anemia and iron deficiency than
      their counterparts infected with P. falciparum alone. CONCLUSIONS/SIGNIFICANCE:
      Our findings suggest that interaction between P. falciparum and light-intensity
      hookworm infections vary with age and, in school-aged children, may benefit the
      host through preventing iron deficiency anemia. This observation warrants
      additional investigation to elucidate the mechanisms and consequences of
      coinfections, as this information could have important implications when
      implementing integrated control measures against malaria and helminthiases.

PMID- 23133693
TI  - Impact of Wolbachia on infection with chikungunya and yellow fever viruses in the
      mosquito vector Aedes aegypti.
AB  - Incidence of disease due to dengue (DENV), chikungunya (CHIKV) and yellow fever
      (YFV) viruses is increasing in many parts of the world. The viruses are primarily
      transmitted by Aedes aegypti, a highly domesticated mosquito species that is
      notoriously difficult to control. When transinfected into Ae. aegypti, the
      intracellular bacterium Wolbachia has recently been shown to inhibit replication
      of DENVs, CHIKV, malaria parasites and filarial nematodes, providing a
      potentially powerful biocontrol strategy for human pathogens. Because the extent
      of pathogen reduction can be influenced by the strain of bacterium, we examined
      whether the wMel strain of Wolbachia influenced CHIKV and YFV infection in Ae.
      aegypti. Following exposure to viremic blood meals, CHIKV infection and
      dissemination rates were significantly reduced in mosquitoes with the wMel strain
      of Wolbachia compared to Wolbachia-uninfected controls. However, similar rates of
      infection and dissemination were observed in wMel infected and non-infected Ae.
      aegypti when intrathoracic inoculation was used to deliver virus. YFV infection,
      dissemination and replication were similar in wMel-infected and control
      mosquitoes following intrathoracic inoculations. In contrast, mosquitoes with the
      wMelPop strain of Wolbachia showed at least a 10(4) times reduction in YFV RNA
      copies compared to controls. The extent of reduction in virus infection depended
      on Wolbachia strain, titer and strain of the virus, and mode of exposure.
      Although originally proposed for dengue biocontrol, our results indicate a
      Wolbachia-based strategy also holds considerable promise for YFV and CHIKV
      suppression.

PMID- 23133692
TI  - Filariasis attenuates anemia and proinflammatory responses associated with
      clinical malaria: a matched prospective study in children and young adults.
AB  - BACKGROUND: Wuchereria bancrofti (Wb) and Mansonella perstans (Mp) are blood
      borne filarial parasites that are endemic in many countries of Africa, including
      Mali. The geographic distribution of Wb and Mp overlaps considerably with that of
      malaria, and coinfection is common. Although chronic filarial infection has been
      shown to alter immune responses to malaria parasites, its effect on clinical and
      immunologic responses in acute malaria is unknown. METHODOLOGY/PRINCIPAL
      FINDINGS: To address this question, 31 filaria-positive (FIL+) and 31 filaria
      negative (FIL-) children and young adults, matched for age, gender and hemoglobin
      type, were followed prospectively through a malaria transmission season. Filarial
      infection was defined by the presence of Wb or Mp microfilariae on calibrated
      thick smears performed between 10 pm and 2 am and/or by the presence of
      circulating filarial antigen in serum. Clinical malaria was defined as axillary
      temperature >=37.5 degrees C or another symptom or sign compatible with malaria
      infection plus the presence of asexual malaria parasites on a thick blood smear.
      Although the incidence of clinical malaria, time to first episode, clinical signs
      and symptoms, and malaria parasitemia were comparable between the two groups,
      geometric mean hemoglobin levels were significantly decreased in FIL- subjects at
      the height of the transmission season compared to FIL+ subjects (11.4 g/dL vs.
      12.5 g/dL, p<0.01). Plasma levels of IL-1ra, IP-10 and IL-8 were significantly
      decreased in FIL+ subjects at the time of presentation with clinical malaria (99,
      2145 and 49 pg/ml, respectively as compared to 474, 5522 and 247 pg/ml in FIL-
      subjects). CONCLUSIONS/SIGNIFICANCE: These data suggest that pre-existent
      filarial infection attenuates immune responses associated with severe malaria and
      protects against anemia, but has little effect on susceptibility to or severity
      of acute malaria infection. The apparent protective effect of filarial infection
      against anemia is intriguing and warrants further study in a larger cohort.

PMID- 23133694
TI  - Chrysomya putoria, a putative vector of diarrheal diseases.
AB  - BACKGROUND: Chrysomya spp are common blowflies in Africa, Asia and parts of South
      America and some species can reproduce in prodigious numbers in pit latrines.
      Because of their strong association with human feces and their synanthropic
      nature, we examined whether these flies are likely to be vectors of diarrheal
      pathogens. METHODOLOGY/PRINCIPAL FINDINGS: Flies were sampled using exit traps
      placed over the drop holes of latrines in Gambian villages. Odor-baited fly traps
      were used to determine the relative attractiveness of different breeding and
      feeding media. The presence of bacteria on flies was confirmed by culture and
      bacterial DNA identified using PCR. A median of 7.00 flies/latrine/day (IQR = 0.0
      25.25) was collected, of which 95% were Chrysomya spp, and of these nearly all
      were Chrysomya putoria (99%). More flies were collected from traps with feces
      from young children (median = 3.0, IQR = 1.75-10.75) and dogs (median = 1.50, IQR
      = 0.0-13.25) than from herbivores (median = 0.0, IQR = 0.0-0.0; goat, horse, cow
      and calf; p<0.001). Flies were strongly attracted to raw meat (median = 44.5, IQR
      = 26.25-143.00) compared with fish (median = 0.0, IQR = 0.0-19.75, ns), cooked
      and uncooked rice, and mangoes (median = 0.0, IQR = 0.0-0.0; p<0.001).
      Escherichia coli were cultured from the surface of 21% (15/72 agar plates) of
      Chrysomya spp and 10% of these were enterotoxigenic. Enteroaggregative E. coli
      were identified by PCR in 2% of homogenized Chrysomya spp, Shigella spp in 1.4%
      and Salmonella spp in 0.6% of samples. CONCLUSIONS/SIGNIFICANCE: The large
      numbers of C. putoria that can emerge from pit latrines, the presence of enteric
      pathogens on flies, and their strong attraction to raw meat and fish suggests
      these flies may be common vectors of diarrheal diseases in Africa.

PMID- 23133695
TI  - [Outcome of cesarean deliveries on cicatricial uterus in a university hospital in
      Burkina Faso].

PMID- 23133696
TI  - The managed hypertensive: the costs of blood pressure control in a Nigerian town.
AB  - BACKGROUND: The health systems designed to cater for patients with chronic
      illnesses like hypertension have not fully evaluated the burden of long term
      therapy and its effect on patient outcome. This study assessed the financial
      implication and cost effectiveness of hypertension treatment in a rural Nigerian
      town. METHODS: A chart review of 250 rural patients with primary hypertension at
      a regional hospital in Southwest Nigeria was conducted. RESULTS: The mean age of
      patients was 61 +/- 11.2 years, 59.2% were females, 67% had an income < ?20,000
      ($133.3) monthly. Diuretics and alpha-Methyl Dopa were the most prescribed drugs.
      The median number of prescribed drugs was two (range1-4). Mean cost of treatment
      was ?1440 +/- 560 ($9.6 +/- 3.7) with 52.8% spending >= 10% of their income on
      treatment. The most cost effective therapies were Methyl Dopa and Diuretics with
      Cost-effectiveness ratios of 8 and 12.8 respectively. Patients with co
      morbidities, stage 2 hypertension and those on three or four drug regimen had
      significantly higher treatment costs. CONCLUSION: The financial burden of long
      term antihypertensive therapy appears substantial, cost reduction strategies are
      needed to optimize hypertension treatment in societies with limited resources.
      Hypertensive management therefore requires a response adapted to the local
      context.

PMID- 23133697
TI  - Pattern of risky sexual behavior and associated factors among undergraduate
      students of the University of Port Harcourt, Rivers State, Nigeria.
AB  - INTRODUCTION: Age at sexual debut had decreased in the developing countries
      recently. Few documented studies have looked into the pattern of risky sexual
      behaviour and associated factors among undergraduate students in Rivers state of
      recent. This study examined the pattern of sexual risky behaviour of
      undergraduate in University of Port-Harcourt, Rivers State, Nigeria. METHODS: A
      descriptive cross sectional survey was adopted and three hundred students were
      purposively recruited. Data were collected by a self -administered semi
      structured questionnaire and analysed using descriptive and chi-square statistics
      at 0.05 significant level. RESULTS: The mean age of respondents was 21.3 +/- 2.8
      years; more than half (57.4%) were females. Almost a quarter (24.5%) was each in
      200 and 300 level of study respectively and more than a quarter (26.7%) lives
      alone. Sixty-one percent of the respondents had ever taken alcohol beverage with
      36.1% of them were current users. More than half (52.0%) the respondents had
      either boy/girlfriend and a total of 144 (52.0%) had ever had sexual intercourse;
      of these 13% reportedly had only one sexual partner in their lifetime; girl/boy
      friend topped the list of their sexual partner; 48.6% respondents were currently
      sexually active and 32% used a form of protection during their last sexual
      activity. The mean age at sexual debut was 17.0 +/- 4.5 years. Few (13.4%) have
      had sex in exchange for gifts and 5.1% of these was with a friend. Higher
      proportions of respondents who reported lifetime use of alcohol were sexually
      active (p<0.005). CONCLUSION: Respondents exhibits risky sexual behavior as more
      had sex without any form of protection. Public enlightenment programmes and
      targeted behavioral change interventions are therefore recommended.

PMID- 23133698
TI  - [Acute intussusception secondary to a lipoma of the small intestine: about a case
      and review of the literature].

PMID- 23133699
TI  - [Obesity in cardiology consultation in Lome: prevalence and risk factors
      associated with cardiovascular disease - study in 1200 patients].

PMID- 23133700
TI  - HIV, Hepatitis B and C viruses' coinfection among patients in a Nigerian tertiary
      hospital.
AB  - INTRODUCTION: Hepatitis co-infection with HIV is associated with increased
      morbidity and mortality. METHODS: This cross sectional study was carried out
      among HIV positive patients and HIV negative blood donors, HIV infected patients
      were recruited from the antiretroviral therapy clinics of the Lagos State
      University Teaching Hospital, in Nigeria. The diagnosis of HIV infection among
      patients and predonation screening of control blood donors was carried out using
      Determine 1/2 screening rapid kits. (Inverness Medical, Japan). Reactive
      patients' sera were confirmed with Enzyme Linked Immunosorbant Assay (Elisa)
      based immuuocomb 1&11 comb firm kits (Orgenics, Israel). Hepatitis B surface
      antigen (HBsAg) and antibodies to hepatitis C virus (anti-HCV) were assayed using
      4(th) generation Dialab Elisa kits for patients and control sera. RESULTS: Dual
      presence of HBsAg and anti-HCV was observed in 4(3.9%) of HIV infected patients,
      while 29(28.4%) and 15(14.7%) were repeatedly reactive for HBsAg and anti-HCV
      respectively. HIV negative blood donor controls have HBsAg and anti-HCV
      prevalence of (22) 6.0% and (3) 0.8% respectively. The prevalence of hepatitis co
      infection is higher among the male study patients 16(50%) than the female 32
      (45.7%).p > 0.001.Data analysis was done with statistical Package for social
      sciences (SPSS,9) and Chi square tests. CONCLUSION: This study reveals a higher
      risk and prevalence of HBV and HCV co infections among HIV infected patients
      compared to HIV negative blood donors p < 0.001.

PMID- 23133701
TI  - Omental patch to control hepatic exsanguination.
AB  - Acute spontaneous intra-abdominal hemorrhage can be life-threatening and is
      particularly challenging in resource-poor settings. A 35-year-old woman presented
      in acutely hypotensive with a distended, rigid abdomen. A paracentesis produced
      >10 mL of non-clotting blood and she was taken to the operating room where
      significant bleeding from a liver cancer nodule was identified. With no other
      option, the generalists doing the surgery used a novel technique - the omental
      patch - to stem the hemorrhage. The patient recovered from the surgery. The
      urgency of performing surgery for spontaneous intraperitoneal hemorrhage
      increases with the scarcity of transfusable blood and general medical officers'
      lack surgical experience. In this case, they rapidly improvised, innovatively
      adapting the omental patch procedure, normally used to close duodenal ulcers, to
      save a life. They had neither performed nor seen this procedure previously. An
      omental patch to stop massive localized intra-abdominal hemorrhage may be an
      important tool for all surgeons.

PMID- 23133702
TI  - [Delivery of conjoined twins fortuitously discovered during labor at the
      University Hospital of Dakar].

PMID- 23133703
TI  - Antibiotic prescribing practice in management of cough and/or diarrhoea in Moshi
      Municipality, Northern Tanzania: cross-sectional descriptive study.
AB  - INTRODUCTION: The increase in resistance of many pathogens to currently available
      antibiotics has been recognized as life-threatening problem. The development of
      drug resistance is promoted by irrational prescribing behavior. Inappropriate use
      of antibiotics is attributed by over-prescription, inadequate dosage and use for
      non-bacterial infections. The purpose of this study was to assess antibiotic
      prescribing practices in the management of diarrhoea and cough among children
      attending hospitals in Moshi municipal, Tanzania. METHODS: We conducted a cross
      sectional descriptive hospital based study, from September 2010 to March 2011.
      All children presenting with diarrhoea and cough, aged between one month and 5
      years attended at the two hospitals were enrolled. Data were collected by a
      standard questionnaire. Information on the prescribed drugs was obtained from
      patient files. RESULTS: A total of 384 children were enrolled. Of these, 326
      (84.9%) received antibiotics; common prescribed antibiotics were penicillins,
      sulphonamides, aminoglycosides and macrolides. Eighty percent of children with
      acute watery diarrhoea and 68.9% with common cold were given antibiotics
      inappropriately. Inappropriate antibiotic prescription was significantly
      associated with prescriber being a clinical officer and assistant medical
      officer, and child having diarrhoea. Inappropriate antibiotic dosage was
      significantly occurred when prescriber was clinical officer with reference to
      medical officer. CONCLUSION: This study observed a high antibiotic prescription
      rate by clinicians and treatment guidelines for management of patients who
      presented with cough and/or diarrhoea are followed. Continuing professional
      development programmes for clinicians on prescription would help in reducing
      irrational prescribing practices.

PMID- 23133704
TI  - [Primary hydatid cyst of the breast].

PMID- 23133705
TI  - A case report of a huge congenital granular cell epulis operated under local
      anesthesia.
AB  - Congenital granular cell epulis (CGCE) is a very rare benign soft tissue lesion
      of the neonate, it most frequently located on the anterior maxillary alveolar
      ridge. It has a female predilection. It is a tumor with no tendency to recur
      after excision. The exact histogenesis of this tumor remains unresolved and it
      may be hamartomata.

PMID- 23133706
TI  - Paraperesis: a rare complication after depressed skull fracture.
AB  - Depressed skull fracture is an inward buckling of the skull bones, often because
      of direct blow to a small surface area of the skull with a blunt object.
      Monoparesis is often among its clinical presentations, but midline depressed
      skull fracture presenting as motor weakness of both lower limbs (Paraperesis) has
      not yet been reported. We report the case of 55 year old male admitted to
      emergency department with alleged history of hit on head by a wooden rod. He had
      pain, mild swelling and a small cut over scalp without any symptoms & signs of
      neurological deficit. On day two of admission patient developed weakness of both
      lower limbs. On CT scan patient had bilateral depressed skull fracture of high
      parietal bone on either side of midline. Patient was managed conservatively, made
      remarkable recovery and was discharged after 2 weeks.

PMID- 23133707
TI  - [Descriptive aspects of HIV/AIDS in patients aged 50 years and over followed at
      the Treatment Center of Bafoussam - Cameroon].

PMID- 23133708
TI  - Molecular epidemiology of group A human rotaviruses in North West region,
      Cameroon.
AB  - BACKGROUND: Rotavirus (RV) is the most common cause of severe diarrhea in
      children <5 years of age worldwide accounting for 527,000 deaths annually. Over
      80% of these deaths occur in South Asia and sub-Saharan Africa. RV vaccines have
      significantly reduced RV-associated morbidity and mortalities in several
      countries like the United States and Mexico while vaccine trials have proved
      efficacious in Ghana and other developing countries. However, there is paucity of
      data on RV infection in Cameroon where diarrhea is a major childhood disease.
      METHODS: A total of 534 stool specimens collected between January 2003 and
      December 2004 from children with acute gastroenteritis in five health districts
      in the NWR of Cameroon were screened for group A human rotavirus antigen by ELISA
      and their electropherotypes determined by Polyacrylamide gel electrophoresis.
      RESULTS: RV was detected in 153 (28.7%) diarrheic specimens with infection
      occurring throughout the year, being more common in children under two years of
      age (P < 0.01) with the highest incidence in the 7-9 months age group (P <0.05).
      Sub clinical infections (9%) occurred mostly in children aged 0 - 6 months old
      (P<0.01). Source of drinking water was not associated with RV infection. Eleven
      electropherotype patterns were detected with predominance of long
      electropherotypes (92.8%) and mixed electropherotypes were seen only in
      hospitalized children. Some isolates showed overlapping or merged genome segments
      7 and 8 or 9 and presenting with 10 segments of the RV genome. CONCLUSION: RV is
      a significant cause of pediatric diarrhea in the NWR affecting mostly children
      under 2 years of age. Continuous RV surveillance and nationwide surveys are
      recommended to improve the health of young children in Cameroon. More research is
      needed to fully characterize the isolated RV strains.

PMID- 23133709
TI  - Circulating vaccine derived poliovirus and the polio eradication endgame.

PMID- 23133710
TI  - [Malignant schwannoma of the sciatic nerve in a child].

PMID- 23133711
TI  - [Castleman disease: unusual location of the chest].

PMID- 23133712
TI  - Factors associated to bed net use in Cameroon: a retrospective study in Mfou
      health district in the Centre Region.
AB  - INTRODUCTION: Insecticide treated net remains a tool of choice for malaria
      prevention in Cameroon. However, data suggests that its use by the population,
      especially vulnerable groups remains low. Moreover, there is a paucity of
      information about factors influencing its use. We sought out to identify factors
      associated with net use in Mfou health district, prior to distribution of long
      lasting insecticides treated nets (LLINs) in households. METHODS: A two-stage
      cluster random sampling was conducted in 4 health areas with an average of 13
      villages each. A total of 541 households were selected and heads interviewed
      using a structured household questionnaire. Data collected were entered into a
      database and multivariate logistic regression analyses of the association between
      net use and explanatory factors were performed using SPSS. RESULTS: Net
      possession and use were respectively, 59.7 and 42.6%; thus, 2 out of 5 people who
      spent the previous night in households, slept under a net. Factors associated
      with net use included: net density>=0.5 (OR=8.88, 95% CI: 6.24-12.64), age>=5
      years (OR=0.37, 95%CI: 0.28-0.47), secondary education (OR=1.41, 95% CI: 1.11
      1.80) compared to primary/no education, parent status (OR=3.32, 95% CI: 2.31
      4.76), house construction (OR=1.37, 95% CI: 1.10-1.71) and environment
      characteristics (OR=1.46, 95% CI: 1.18-1.80). CONCLUSION: These data suggest that
      a universal coverage with one LLIN for two people should be achieved in
      households. Then, malaria health education should be conducted to re-enforce net
      use among school-aged children and adolescents, as well as older household
      members. Moreover, management of environment and improvement in houses
      construction are necessary.

PMID- 23133713
TI  - Effect of dietary calcium on spinal bone fusion in an ovariectomized rat model.
AB  - OBJECTIVE: To evaluate the effect of calcium supplementation on spinal bone
      fusion in ovariectomized (OVX) rats. METHODS: Sixteen female Sprague Dawley rats
      underwent bilateral ovariectomy at 12 weeks of age to induce osteoporosis and
      were randomly assigned to two groups : control group (n=8) and calcium
      supplemented group (OVX-Ca, n=8). Autologous spinal bone fusion surgery was
      performed on both groups 8 weeks later. After fusion surgery, the OVX-Ca group
      was supplemented with calcium in drinking water for 8 weeks. Blood was obtained 4
      and 8 weeks after fusion surgery. Eight weeks after fusion surgery, the rats were
      euthanized and the L4-5 spine removed. Bone fusion status and fusion volume were
      evaluated by manual palpation and three-dimensional computed tomography. RESULTS:
      The mean fusion volume in the L4-5 spine was significantly greater in the OVX-Ca
      group (71.80+/-8.06 mm(3)) than in controls (35.34+/-8.24 mm(3)) (p<0.01). The
      level of osteocalcin, a bone formation marker, was higher in OVX-Ca rats than in
      controls 4 weeks (610.08+/-10.41 vs. 551.61+/-12.34 ng/mL) and 8 weeks (552.05+/
      19.67 vs. 502.98+/-22.76 ng/mL) after fusion surgery (p<0.05). The level of C
      terminal telopeptide fragment of type I collagen, a bone resorption marker, was
      significantly lower in OVX-Ca rats than in controls 4 weeks (77.07+/-12.57 vs.
      101.75+/-7.20 ng/mL) and 8 weeks (69.58+/-2.45 vs. 77.15+/-4.10 ng/mL) after
      fusion surgery (p<0.05). A mechanical strength test showed that the L4-5
      vertebrae in the OVX-Ca group withstood a 50% higher maximal load compared with
      the controls (p<0.01). CONCLUSION: Dietary calcium given to OVX rats after lumbar
      fusion surgery improved fusion volume and mechanical strength in an
      ovariectomized rat model.

PMID- 23133714
TI  - Delayed cranial nerve palsy after microvascular decompression for hemifacial
      spasm.
AB  - OBJECTIVE: Microvascular decompression (MVD) for hemifacial spasm (HFS) is a safe
      and effective treatment with favorable outcomes. The purpose of this study was to
      evaluate the incidence of delayed cranirve ( VI, VII, and VIII ) palsy following
      MVD and its clinical courses. METHODS: Between January 1998 and December 2009,
      1354 patients underwent MVD for HFS at our institution. Of them, 100 patients
      (7.4%) experienced delayed facial palsy (DFP), one developed sixth nerve palsy,
      and one patient had delayed hearing loss. RESULTS: DFP occurred between
      postoperative day number 2 and 23 (average 11 days). Ninety-two patients (92%)
      completely recovered; however, House-Brackmann grade II facial weakness remained
      in eight other patients (8%). The time to recovery averaged 64 days (range, 16
      days to 9 months). Delayed isolated sixth nerve palsy recovered spontaneously
      without any medical or surgical treatment after 8 weeks, while delayed hearing
      loss did not improve. CONCLUSION: Delayed cranial nerve (VI, VII, and VIII)
      palsies can occur following uncomplicated MVD for HFS. DFP is not an unusual
      complication after MVD, and prognosis is fairly good. Delayed sixth nerve palsy
      and delayed hearing loss are extremely rare complications after MVD for HFS. We
      should consider the possibility of development of these complications during the
      follow up for MVD.

PMID- 23133715
TI  - The clinical efficacy of decompressive craniectomy in patients with an internal
      carotid artery territory infarction.
AB  - OBJECTIVE: To evaluate the surgical efficacy of and factors associated with
      decompressive craniectomy in patients with an internal carotid artery (ICA)
      territory infarction. METHODS: Seventeen patients (8 men and 9 women, average age
      61.53 years, range 53-77 years) were treated by decompressive craniectomy for an
      ICA territory infarction at our institute. We retrospectively reviewed medical
      records, radiological findings, and National Institutes of Health Stroke Scale
      (NIHSS) at presentation and before surgery. Clinical outcomes were assessed using
      the Glasgow Outcome Scale (GOS). RESULTS: Of the 17 patients, 15 (88.24%)
      achieved a poor outcome (Group A, GOS 1-3) and 2 (11.76%) a good outcome (Group
      B, GOS 4-5). The mortality rate at one month after surgery was 52.9%. Average
      preoperative NIHSS was 27.6+/-10.88% in group A and 10+/-4.24% in group B. Mean
      cerebral infarction fraction at the septum pellucidum level before surgery in
      group A and B were 33.67% and 23.72%, respectively. Mean preoperative NIHSS
      (p=0.019) and cerebral infarction fraction at the septum pellucidum level
      (p=0.017) were found to be significantly associated with a better outcome.
      However, no preexisting prognostic factor was found to be of statistical
      significance. CONCLUSION: The rate of mortality after ICA territory infarction
      treatment is relatively high, despite positive evidence for surgical
      decompression, and most survivors experience severe disabilities. Our findings
      caution that careful consideration of prognostic factors is required when
      considering surgical treatment.

PMID- 23133716
TI  - Anatomical morphometric study of the cervical uncinate process and surrounding
      structures.
AB  - OBJECTIVE: The purpose of this study is to elucidate the anatomic relationships
      between the uncinate process and surrounding neurovascular structures to prevent
      possible complications in anterior cervical surgery. METHODS: Twenty-eight
      formalin-fixed cervical spines were removed from adult cadavers and were studied.
      The authors investigated the morphometric relationships between the uncinate
      process, vertebral artery and adjacent nerve roots. RESULTS: The height of the
      uncinate process was 5.6-7.5 mm and the width was 5.8-8.0 mm. The angle between
      the posterior tip of the uncinate process and vertebral artery was 32.2-42.4
      degrees . The distance from the upper tip of the uncinate process to the
      vertebral body immediately above was 2.1-3.3 mm, and this distance was narrowest
      at the fifth cervical vertebrae. The distance from the posterior tip of the
      uncinate process to the nerve root was 1.3-2.0 mm. The distance from the uncinate
      process to the vertebral artery was measured at three different points of the
      uncinate process : upper-posterior tip, lateral wall and the most antero-medial
      point of the uncinate process, and the distances were 3.6-6.1 mm, 1.7-2.8 mm, and
      4.2-5.7 mm, respectively. The distance from the uncinate process tip to the
      vertebral artery and the angle between the uncinate process tip and vertebral
      artery were significantly different between the right and left side. CONCLUSION:
      These data provide guidelines for anterior cervical surgery, and will aid in
      reducing neurovascular injury during anterior cervical surgery, especially in
      anterior microforaminotomy.

PMID- 23133717
TI  - Unruptured Supraclinoid Internal Carotid Artery Aneurysm Surgery : Superciliary
      Keyhole Approach versus Pterional Approach.
AB  - OBJECTIVE: A superciliary keyhole approach is an attractive, minimally invasive
      surgical technique, yet the procedure is limited due to a small cranial opening.
      Nonetheless, an unruptured supraclinoid internal carotid artery (ICA) aneurysm
      can be an optimal surgical target of a superciliary approach as it is located in
      the center of the surgical view and field. Therefore, this study evaluated the
      feasibility and surgical outcomes of a superciliary keyhole approach for
      unruptured ICA aneurysms. METHODS: The authors report on a consecutive series of
      patients who underwent a superciliary approach for clipping unruptured ICA
      aneurysms between January 2007 and February 2012. The data were compared with a
      historical control group who underwent a pterional approach between January 2003
      and December 2006. RESULTS: In the superciliary group, a total of 71 aneurysms
      were successfully clipped without a residual sac in 70 patients with a mean age
      of 57 years (range, 37-75 years). The maximum diameter of the aneurysms ranged
      from 4 mm to 14 mm (mean+/-standard deviation, 6.6+/-2.3 mm). No direct mortality
      or permanent morbidity was related to the surgery. The superciliary approach
      demonstrated statistically significant advantages over the pterional approach,
      including a shorter operative duration (mean, 100 min), no intraoperative blood
      transfusions, and no postoperative epidural hemorrhages. CONCLUSION: A
      superciliary keyhole approach provides a sufficient surgical corridor to clip
      most unruptured supraclinoid ICA aneurysms in a minimally invasive manner.

PMID- 23133718
TI  - Seizures after spontaneous intracerebral hemorrhage.
AB  - OBJECTIVE: In patients with spontaneous intracerebral hemorrhage (ICH), the risk
      factors for seizure and the effect of prophylactic anticonvulsants are not well
      known. This study aimed to determine the risk factor for seizures and the role
      for prophylactic anticonvulsants after spontaneous ICH. METHODS: Between 2005 and
      2010, 263 consecutive patients with spontaneous ICH were retrospectively assessed
      with a mean follow-up of 19.5 months using medical records, updated clinical
      information and, when necessary, direct patient contact. The seizures were
      classified as early (within 1 week of ICH) or late (more than 1 week after ICH).
      The outcomes were measured with the Glasgow Outcome Scale at discharge and the
      modified Rankin Scale (mRS) at both 2 weeks and discharge. RESULTS: Twenty-two
      patients (8.4%; 9 patients with early seizures and 13 patients with late
      seizures) developed seizures after spontaneous ICH. Out of 263 patients,
      prophylactic anticonvulsants were administered in 216 patients. The prophylactic
      anticonvulsants were not associated with a reduced risk of early (p=0.094) or
      late seizures (p=0.326). Instead, the factors associated with early seizure were
      cortical involvement (p<0.001) and younger age (60 years or less) (p=0.046). The
      risk of late seizure was increased by cortical involvement (p<0.001) and
      communicating hydrocephalus (p=0.004). The prophylactic anticonvulsants were
      associated with a worse mRS at 2 weeks (p=0.024) and at last follow-up (p=0.034).
      CONCLUSION: Cortical involvement may be a factor for provoked seizures. Although
      the incidence of early seizures tended to decrease in patients prescribed
      prophylactic anticonvulsants, no statistical difference was found.

PMID- 23133719
TI  - Spontaneous cerebellar hemorrhage with the fourth ventricular hemorrhage : risk
      factors associated with ventriculoperitoneal shunt.
AB  - OBJECTIVE: The purposes of this study are to investigate the factors that may be
      related to ventriculoperitoneal (VP) shunt in patients with cerebellar hematoma
      and the effect of severe fourth ventricular hemorrhage, causing obstructive
      hydrocephalus on subsequent VP shunt performance. METHODS: This study included 31
      patients with spontaneous cerebellar hematoma and concomitant fourth ventricular
      hemorrhage, who did not undergo a surgical evacuation of hematoma. We divided
      this population into two groups; the VP shunt group, and the non-VP shunt group.
      The demographic data, radiologic findings, and clinical factors were compared in
      each group. The location of the hematoma (whether occupying the cerebellar
      hemisphere or the vermis) and the degree of the fourth ventricular obstruction
      were graded respectively. The intraventricular hemorrhage (IVH) score was used to
      assess the IVH severity. RESULTS: Ten out of 31 patients underwent VP shunt
      operations. The midline location of cerebellar hematoma, the grade of fourth
      ventricle obstruction, and IVH severity were significantly correlated with that
      of VP shunt operation (p=0.015, p=0.013, p=0.028). The significant variables into
      a logistic regression multivariate model resulted in statistical significance for
      the location of cerebellar hemorrhage [p=0.05; odds ratio (OR), 8.18; 95%
      confidence interval (CI), 1.00 to 67.0], the grade of fourth ventricle
      obstruction (p=0.044; OR, 19.26; 95% CI, 1.07 to 346.6). CONCLUSION: The location
      of the cerebellar hematoma on CT scans and the degree of fourth ventricle
      obstruction by IVH were useful signs for the selection of VP shunt operation in
      patients with spontaneous cerebellar hematoma and concomitant acute
      hydrocephalus.

PMID- 23133720
TI  - Clinical and neuroimaging outcomes of surgically treated intracranial cysts in
      110 children.
AB  - OBJECTIVE: The indications and optimal surgical treatments for intracranial cysts
      are controversial. In the present study, we describe long-term clinical and
      neuroimaging results of surgically treated intracranial cysts in children. The
      goal of this study is to contribute to the discussion of the debate. METHODS:
      This study included 110 pediatric patients that underwent surgeries to treat
      intracranial cysts. Endoscopic cyst fenestrations were performed in 71 cases,
      while craniotomies and cyst excisions (with or without fenestrations) were
      performed in 30 patients. Cystoperitoneal shunts were necessary for nine
      patients. Long-term results were retrospectively assessed with medical and
      neuroimaging records. RESULTS: Clinical and radiological improvement was reported
      in 87.3% and 92.8% of cases, respectively, after endoscopic neurosurgery, and in
      93.3% and 100% using open microsurgery whereas 88.9% and 85.7% after shunt
      operation. There were no statistical differences in clinical outcomes (p=0.710)
      or volume reductions (p=0.177) among the different surgeries. There were no
      mortalities or permanent morbidities, but complications such as shunt
      malfunctions, infections, and subdural hematomas were observed in 56% of the
      patients that had shunt operations. A total of 13 patients (11.8%) underwent
      additional surgeries due to recurrences or treatment failures. The type of
      surgery performed did not influence the recurrence rate (p=0.662) or the failure
      rate (p=0.247). CONCLUSION: Endoscopic neurosurgeries are less invasive than
      microsurgeries and are at least as effective as open surgeries. Thus, given the
      advantages and complications of these surgical techniques, we suggest that
      endoscopic fenestration should be the first treatment attempted in children with
      intracranial cysts.

PMID- 23133721
TI  - Multiple gamma knife radiosurgery for multiple metachronous brain metastases
      associated with lung cancer : survival time.
AB  - OBJECTIVE: We compared the survival time between patients with multiple gamma
      knife radiosurgery (GKRS) and patients with a single GKRS plus whole brain
      radiation therapy (WBRT), in patients with multiple metachronous brain metastases
      from lung cancer. METHODS: From May 2006 to July 2010, we analyzed 31 patients
      out of 112 patients who showed multiple metachronous brain metastases. 20 out of
      31 patients underwent multiple GKRS (group A) and 11 patients underwent a single
      GKRS plus WBRT (group B). We compared the survival time between group A and B.
      Kaplan-Meier method and Cox proportional hazards were used to analyze
      relationship between survival and 1) the number of lesions in each patient, 2)
      the average volume of lesions in each patient, 3) the number of repeated GKRS,
      and 4) the interval of development of new lesions, respectively. RESULTS: Median
      survival time was 18 months (range 6-50 months) in group A and 6 months (range 3
      18 months) in group B. Only the average volume of individual lesion (over 10 cc)
      was negatively related with survival time according to Kaplan-Meier method. Cox
      proportional hazard ratio of each variable was 1.1559 for the number of lesions,
      1.0005 for the average volume of lesions, 0.0894 for the numbers of repeated
      GKRS, and 0.5970 for the interval of development of new lesions. CONCLUSION: This
      study showed extended survival time in group A compared with group B. Our result
      supports that multiple GKRS is of value in extending the survival time in
      patients with multiple metachronous brain metastases, and that the number of the
      lesions and the frequency of development of new lesions are not an obstacle in
      treating patients with GKRS.

PMID- 23133722
TI  - The analysis of patterns and risk factors of newly developed vertebral
      compression fractures after percutaneous vertebroplasty.
AB  - OBJECTIVE: The purpose of this study was to investigate the patterns and the risk
      factors of newly developed vertebral compression fractures (VCFs) after
      percutaneous vertebroplasty (PVP). METHODS: We performed a retrospective review
      of the 244 patients treated with PVP from September 2006 to February 2011. Among
      these patients, we selected 49 patients with newly developed VCFs following PVP
      as the new VCFs group, and the remaining 195 patients as the no VCFs group. The
      new VCFs group was further divided into 2 groups : an adjacent fractures group
      and a nonadjacent fractures group. The following data were collected from the
      groups : age, gender, body weight/height, body mass index (BMI), bone mineral
      density (BMD) score of the spine and femur, level of initial fracture,
      restoration rate of anterior/middle vertebral height, and intradiscal cement
      leakage, volume of polymethylmethacrylate (PMMA). RESULTS: Age, gender, mean body
      height/weight, mean BMI and volume of PMMA of each of the group are not
      statistically significantly associated with fractures. In comparison between the
      new VCFs group and the no VCFs group, lower BMD, intradiscal cement leakage and
      anterior vertebral height restoration were the significant predictive factors of
      the fracture. In addition, new VCFs occurrence at the adjacent spines was
      statistically significant, when the initial fracture levels were confined to the
      thoracolumbar junction, among the subgroups of new VCFs. CONCLUSION: Lower spinal
      BMD, the greater anterior vertebral height restoration rate and intradiscal
      cement leakage were confirmed as risk factors for newly formed VCFs after PVP.

PMID- 23133723
TI  - Comparison of posterior fixation alone and supplementation with posterolateral
      fusion in thoracolumbar burst fractures.
AB  - OBJECTIVE: We compared the radiological and clinical outcomes between patients
      who underwent posterior fixation alone and supplemented with fusion following the
      onset of thoracolumbar burst fractures. In addition, we also evaluated the
      necessity of posterolateral fusion for patients treated with posterior pedicle
      screw fixation. METHODS: From January 2007 to December 2009, 46 consecutive
      patients with thoracolumbar burst fracture were included in this study. On the
      basis of posterolateral fusion, we divided our patients into the non-fusion group
      and the fusion group. The radiological assessment was performed according to the
      Cobb's method, and results were obtained at immediately, 3, 6, 12 months after
      surgery. The clinical outcomes were evaluated using the modified Mcnab criteria
      at the final follow-up. RESULTS: The demographic data and the mean follow-up
      period were similar between the two groups. Patients of both groups achieved
      satisfactory clinical outcomes. The mean loss of kyphosis correction showed that
      patients of both groups experienced loss of correction with no respect to whether
      they underwent the posterolateral fusion. There was no significant difference in
      the degree of loss of correction at any time points of the follow-up between the
      two groups. In addition, we also compared the effect of fixed levels (i.e., short
      versus long segment) on loss of correction between the two groups and there was
      no significant difference. There were no major complications postoperatively and
      during follow-up period. CONCLUSION: We suggest that posterolateral fusion may be
      unnecessary for patients with thoracolumbar burst fractures who underwent
      posterior pedicle screw fixation.

PMID- 23133724
TI  - Bone cement-augmented short segment fixation with percutaneous screws for
      thoracolumbar burst fractures accompanied by severe osteoporosis.
AB  - OBJECTIVE: The purpose of this study was to determine the efficacy of bone cement
      augmented short segment fixation using percutaneous screws for thoracolumbar
      burst fractures in a background of severe osteoporosis. METHODS: Sixteen patients
      with a single-level thoracolumbar burst fracture (T11-L2) accompanying severe
      osteoporosis treated from January 2008 to November 2009 were prospectively
      analyzed. Surgical procedures included postural reduction for 3 days and bone
      cement augmented percutaneous screw fixation at the fracture level and at
      adjacent levels without bone fusion. Due to the possibility of implant failure,
      patients underwent implant removal 12 months after screw fixation. Imaging and
      clinical findings, including involved vertebral levels, local kyphosis, canal
      encroachment, and complications were analyzed. RESULTS: Prior to surgery, mean
      pain score (visual analogue scale) was 8.2 and this decreased to a mean of 2.2 at
      12 months after screw fixation. None of the patients complained of pain worsening
      during the 6 months following implant removal. The percentage of canal compromise
      at the fractured level improved from a mean of 41.0% to 18.4% at 12 months after
      surgery. Mean kyphotic angle was improved significantly from 19.8 degrees  before
      surgery to 7.8 at 12 months after screw fixation. Canal compromise and kyphotic
      angle improvements were maintained at 6 months after implant removal. No
      significant neurological deterioration or complications occurred after screw
      removal in any patient. CONCLUSION: Bone cement augmented short segment fixation
      using a percutaneous system can be an alternative to the traditional open
      technique for the management of selected thoracolumbar burst fractures
      accompanied by severe osteoporosis.

PMID- 23133725
TI  - Posterior interspinous fusion device for one-level fusion in degenerative lumbar
      spine disease : comparison with pedicle screw fixation - preliminary report of at
      least one year follow up.
AB  - OBJECTIVE: Transpedicular screw fixation has some disadvantages such as
      postoperative back pain through wide muscle dissection, long operative time, and
      cephalad adjacent segmental degeneration (ASD). The purposes of this study are
      investigation and comparison of radiological and clinical results between
      interspinous fusion device (IFD) and pedicle screw. METHODS: From Jan. 2008 to
      Aug. 2009, 40 patients underwent spinal fusion with IFD combined with posterior
      lumbar interbody fusion (PLIF). In same study period, 36 patients underwent
      spinal fusion with pedicle screw fixation as control group. Dynamic lateral
      radiographs, visual analogue scale (VAS), and Korean version of the Oswestry
      disability index (K-ODI) scores were evaluated in both groups. RESULTS: The
      lumbar spine diseases in the IFD group were as followings; spinal stenosis in 26,
      degenerative spondylolisthesis in 12, and intervertebral disc herniation in 2.
      The mean follow up period was 14.24 months (range; 12 to 22 months) in the IFD
      group and 18.3 months (range; 12 to 28 months) in pedicle screw group. The mean
      VAS scores was preoperatively 7.16+/-2.1 and 8.03+/-2.3 in the IFD and pedicle
      screw groups, respectively, and improved postoperatively to 1.3+/-2.9 and 1.2+/
      3.2 in 1-year follow ups (p<0.05). The K-ODI was decreased significantly in an
      equal amount in both groups one year postoperatively (p<0.05). The statistics
      revealed a higher incidence of ASD in pedicle screw group than the IFD group
      (p=0.029). CONCLUSION: Posterior IFD has several advantages over the pedicle
      screw fixation in terms of skin incision, muscle dissection and short operative
      time and less intraoperative estimated blood loss. The IFD with PLIF may be a
      favorable technique to replace the pedicle screw fixation in selective case.

PMID- 23133726
TI  - A surgical option for multilevel anterior lumbar interbody fusion with ponte
      osteotomy to achieve optimal lumbar lordosis and sagittal balance.
AB  - OBJECTIVE: To document lumbar lordosis (LL) of the spine and its change during
      surgeries with the different height but the same angle setting of the anterior
      cage. Additionally, we attempted to determine if sufficient LL is achieved at
      different cage heights and to quantify the change in LL during multi-level
      anterior lumbar interbody fusion (ALIF). METHODS: The medical records and
      radiographs of 42 patients who underwent more than 2 level ALIFs between 2008 and
      2009 were retrospectively reviewed. We evaluated 3 parameters seen on lateral
      whole spine radiographs : LL, pelvic incidence (PI), and sagittal vertical axis
      (SVA). The mean follow-up time was 28.1 months and the final follow-up
      radiographs of all patients were reviewed at least 2 years after surgery.
      Statistical analysis was performed using the paired t-tests. RESULTS: Lumbar
      lordosis had changed up to 30 degrees immediately and 2 years after surgery
      (preoperative mean LL, SVA : 22.45 degrees, 112.31 mm; immediate postoperative
      mean LL, SVA : 54.45 degrees, 37.36 mm; final follow-up mean LL, SVA : 49.56
      degrees, 26.95 mm). Our goal of LL is to obtain as much PI as possible,
      preoperative mean PI value was 55.38+/-3.35. The pre-operative and two year post
      surgery follow-up mean of the Japanese Orthopedic Association score were 9.2+/
      0.6 and 13.2+/-0.6 (favorable outcome rate : 95%), respectively. In addition, we
      were able to obtain good clinical outcomes and sagittal balance with a subsidence
      rate of 22.7%. CONCLUSION: We were able to achieve sufficient LL, such that it
      was similar to the PI, utilizing multi-level ALIF with the use of a tall cage
      with the same angle setting of the cage. We have found out that achieving
      sufficient lumbar lordosis and sagittal balance require an anterior lumbar cage
      with high angle and height.

PMID- 23133727
TI  - Efficacy of the Disappearance of Lateral Spread Response before and after
      Microvascular Decompression for Predicting the Long-Term Results of Hemifacial
      Spasm Over Two Years.
AB  - OBJECTIVE: The purpose of this large prospective study is to assess the
      association between the disappearance of the lateral spread response (LSR) before
      and after microvascular decompression (MVD) and clinical long term results over
      two years following hemifacial spasm (HFS) treatment. METHODS: Continuous intra
      operative monitoring during MVD was performed in 244 consecutive patients with
      HFS. Patients with persistent LSR after decompression (n=22, 9.0%), without LSR
      from the start of the surgery (n=4, 1.7%), and with re-operation (n=15, 6.1%) and
      follow-up loss (n=4, 1.7%) were excluded. For the statistical analysis, patients
      were categorized into two groups according to the disappearance of their LSR
      before or after MVD. RESULTS: Intra-operatively, the LSR was checked during
      facial electromyogram monitoring in 199 (81.5%) of the 244 patients. The mean
      follow-up duration was 40.9+/-6.9 months (range 25-51 months) in all the
      patients. Among them, the LSR disappeared after the decompression (Group A) in
      128 (64.3%) patients; but in the remaining 71 (35.6%) patients, the LSR
      disappeared before the decompression (Group B). In the post-operative follow-up
      visits over more than one year, there were significant differences between the
      clinical outcomes of the two groups (p<0.05). CONCLUSION: It was observed that
      the long-term clinical outcomes of the intra-operative LSR disappearance before
      and after MVD were correlated. Thus, this factor may be considered a prognostic
      factor of HFS after MVD.

PMID- 23133728
TI  - Locations and clinical significance of non-hemorrhagic brain lesions in diffuse
      axonal injuries.
AB  - OBJECTIVE: Detection of focal non-hemorrhagic lesion (NHL) has become more
      efficient in diffuse axonal injury (DAI) patients using an MRI. The aims of this
      study are to find out the radiological distribution, progress of NHL and its
      clinical significance. METHODS: Between September 2005 and October 2011, 32
      individuals with NHLs on brain MRI were enrolled. NHLs were classified by brain
      location into 4 major districts and 13 detailed locations including cortical and
      subcortical, corpus callosum, deep nuclei and adjacent area, and brainstem. The
      severity of NHL was scored from grades 1 to 4, according to the number of
      districts involved. Fourteen patients with NHL were available for MRI follow-up
      and an investigation of the changes was conducted. RESULTS: Thirty-two patients
      had 59 NHLs. The most common district of NHL was cortical and subcortical area;
      15 patients had 20 NHSs. However the most common specific location was the
      splenium of the corpus callosum; 14 patients had 14 lesions. The more lesions
      patients had, the lower the GCS, however, this was not a statistically meaningful
      difference. On follow-up MRI in 14 patients, out of 24 lesions, 13 NHLs resolved,
      5 showed cystic change, and 6 showed atrophic changes. CONCLUSION: NHLs were
      located most commonly in the splenium and occur frequently in the thalamus and
      the mesial temporal lobe. Because most NHS occur concomitantly with hemorrhagic
      lesions, it was difficult to determine their effects on prognosis. Since most
      NHLs resolve completely, they are probably less significant to prognosis than
      hemorrhagic lesions.

PMID- 23133729
TI  - Morphometric Relationship between the Cervicothoracic Cord Segments and Vertebral
      Bodies.
AB  - OBJECTIVE: The objective of this study was to investigate the morphologic
      characteristics between the vertebral body and the regions of the cervical and
      thoracic spinal cords where each rootlets branch out. METHODS: Sixteen adult
      cadavers (12 males and 4 females) with a mean age of 57.9 (range of 33 to 70
      years old) were used in this study. The anatomical relationship between the exit
      points of the nerve roots from the posterior root entry zone at each spinal cord
      segment and their corresponding relevant vertebral bodies were also analyzed.
      RESULTS: Vertical span of the posterior root entry zone between the upper and
      lower rootlet originating from each spinal segment ranged from 10-12 mm. The
      lengths of the rootlets from their point of origin at the spinal cord to their
      entrance into the intervertebral foramen were 5.9 mm at the third cervical nerve
      root and increased to 14.5 mm at the eighth cervical nerve root. At the lower
      segments of the nerve roots (T3 to T12), the posterior root entry zone of the
      relevant nerve roots had a corresponding anatomical relationship with the
      vertebral body that is two segments above. The posterior root entry zones of the
      sixth (94%) and seventh (81%) cervical nerve roots were located at a vertebral
      body a segment above from relevant segment. CONCLUSION: Through these
      investigations, a more accurate diagnosis, the establishment of a better
      therapeutic plan, and a decrease in surgical complications can be expected when
      pathologic lesions occur in the spinal cord or vertebral body.

PMID- 23133730
TI  - Meningeal layers around anterior clinoid process as a delicate area in extradural
      anterior clinoidectomy : anatomical and clinical study.
AB  - OBJECTIVE: Removal of the anterior clinoid process (ACP) is an essential process
      in the surgery of giant or complex aneurysms located near the proximal internal
      carotid artery or the distal basilar artery. An extradural clinoidectomy must be
      performed within the limits of the meningeal layers surrounding the ACP to
      prevent morbid complications. To identify the safest method of extradural
      exposure of the ACP, anatomical studies were done on cadaver heads. METHODS:
      Anatomical dissections for extradural exposure of the ACP were performed on both
      sides of seven cadavers. Before dividing the frontotemporal dural fold (FTDF), we
      measured its length from the superomedial apex attached to the periorbita to the
      posterolateral apex which connects to the anterosuperior end of the cavernous
      sinus. RESULTS: The average length of the FTDF on cadaver dissections was 7 mm on
      the right side and 7.14 mm on the left side. Cranial nerves were usually exposed
      when cutting FTDF more than 7 mm of the FTDF. CONCLUSION: The most delicate area
      in an extradural anterior clinoidectomy is the junction of the FTDF and the
      anterior triangular apex of the cavernous sinus. The FTDF must be cut from the
      anterior side of the triangle at the periorbital side rather than from the dural
      side. The length of the FTDF incision must not exceed 7 mm to avoid cranial nerve
      injury.

PMID- 23133731
TI  - Long-term incidence and predicting factors of cranioplasty infection after
      decompressive craniectomy.
AB  - OBJECTIVE: The predictors of cranioplasty infection after decompressive
      craniectomy have not yet been fully characterized. The objective of the current
      study was to compare the long-term incidences of surgical site infection
      according to the graft material and cranioplasty timing after craniectomy, and to
      determine the associated factors of cranioplasty infection. METHODS: A
      retrospective cohort study was conducted to assess graft infection in patients
      who underwent cranioplasty after decompressive craniectomy between 2001 and 2011
      at a single-center. From a total of 197 eligible patients, 131 patients
      undergoing 134 cranioplasties were assessed for event-free survival according to
      graft material and cranioplasty timing after craniectomy. Kaplan-Meier survival
      analysis and Cox regression methods were employed, with cranioplasty infection
      identified as the primary outcome. Secondary outcomes were also evaluated,
      including autogenous bone resorption, epidural hematoma, subdural hematoma and
      brain contusion. RESULTS: The median follow-up duration was 454 days (range 10 to
      3900 days), during which 14 (10.7%) patients suffered cranioplasty infection.
      There was no significant difference between the two groups for event-free
      survival rate for cranioplasty infection with either a cryopreserved or
      artificial bone graft (p=0.074). Intergroup differences according to cranioplasty
      time after craniectomy were also not observed (p=0.083). Poor neurologic outcome
      at cranioplasty significantly affected the development of cranioplasty infection
      (hazard ratio 5.203, 95% CI 1.075 to 25.193, p=0.04). CONCLUSION: Neurologic
      status may influence cranioplasty infection after decompressive craniectomy. A
      further prospective study about predictors of cranioplasty infection including
      graft material and cranioplasty timing is necessary.

PMID- 23133732
TI  - A Rathke's Cleft Cyst Presenting with Apoplexy.
AB  - The occurrence of symptomatic pituitary hemorrhage into a Rathke's cleft cyst
      (RCC) is extremely rare. The author reports an interesting case of intra- and
      suprasellar RCC presented with features of pituitary apoplexy. This 62-year-old
      woman suffered acute headache, mental confusion, and partial hypopituitarism. The
      characteristics of the magnetic resonance imaging seemed most compatible with a
      hemorrhagic pituitary adenoma. Transsphenoidal drainage of the cyst contents
      confirmed the diagnosis of hemorrhagic RCC and resolved the symptoms. All
      published data on this rare clinical entity are extracted and reviewed.

PMID- 23133733
TI  - Spinal epidural arteriovenous hemangioma mimicking lumbar disc herniation.
AB  - A spinal epidural hemangioma is rare. In this case, a 51 year-old female patient
      had low back pain and right thigh numbness. She was initially misdiagnosed as
      having a ruptured disc with possible sequestration of granulation tissue
      formation due to the limited number of spinal epidural hemangiomas and little
      known radiological findings. Because there are no effective diagnostic tools to
      verify the hemangioma, more effort should be put into preoperative imaging tests
      to avoid misdiagnosis and poor decisions).

PMID- 23133734
TI  - Eosinophilic myelitis in the cervical cord mimicking intramedullary cord tumor.
AB  - Eosinophilic myelitis (EM) or atopic myelitis is a rare disease characterized by
      a myelitic condition in the spinal cord combined with allergic process. This
      disease has specific features of elevated serum IgE level, active reaction to
      mite specific antigen and stepwise progression of mostly the sensory symptoms.
      Toxocariasis can be related with a form of EM. This report describes two cases of
      cervical eosinophilic myelitis initially considered as intramedullary tumors.
      When a differential diagnosis of the intramedullary spinal cord lesion is in
      doubt, evaluation for eosinophilic myelitis and toxocariasis would be beneficial.

PMID- 23133735
TI  - Transorbital penetrating intracranial injury by a chopstick.
AB  - A 38-year-old man fell from a chair with a chopstick in his hand. The chopstick
      penetrated his left eye. He noticed pain, swelling, and numbness around his left
      eye. On physical examination, a linear wound was noted at the medial aspect of
      the left eyelid. Noncontrast computed tomography (CT) study showed a linear
      hypodense structure extending from the medial aspect of the left orbit to the
      occipital bone, suggesting a foreign body. This foreign body was hyperdense
      relative to normal parenchyma. From a CT scan with 3-dimensional reconstruction,
      the foreign body was found to be passing through the optic canal into the
      cranium. The clear plastic chopstick was withdrawn without difficulty. The
      patient was discharged home 3 weeks after his surgery. A treatment plan for a
      transorbital penetrating injury should be determined by a multidisciplinary team,
      with input from neurosurgeons and ophthalmologists.

PMID- 23133736
TI  - Intradural extramedullary and subcutaneous tumors in neonate : atypical myxoid
      spindle cell neoplasm.
AB  - Tumors of the central nervous system are common in the pediatric population and
      constitute the second most prevalent tumor type in children. Within this group,
      spinal cord tumors are relatively rare and account for 1 to 10% of all pediatric
      central nervous system tumors. We describe a very rare case of an intradural
      extramedullary spinal cord tumor with a subcutaneous mass and discuss its
      clinical presentation, pathogenesis, and treatment. A male infant was delivered
      normally, with uneventful development. At 16 days post-delivery, his family took
      him to a pediatrician because of a mass on his upper back. Magnetic resonance
      imaging of the thoracic spine revealed a well-demarcated soft-tissue mass with
      central cystic change or necrosis at the subcutaneous layer of the posterior back
      (T2-7 level). Another mass was found with a fat component at the spinal canal of
      the T1-3 level, which was intradural extramedullary space. After six weeks, the
      spinal cord tumor and subcutaneous mass were grossly total resected; pathologic
      findings indicated an atypical myxoid spindle cell neoplasm, possibly nerve
      sheath in type. The final diagnosis of the mass was an atypical myxoid spindle
      cell neoplasm. The postoperative course was uneventful, and the patient was
      discharged after nine days without any neurological deficit. We report a rare
      case of an intradural extramedullary spinal tumor with subcutaneous mass in a
      neonate. It is necessary to monitor the patient's status by examining consecutive
      radiologic images, and the symptoms and neurological changes should be observed
      strictly during long-term follow-up.

PMID- 23133737
TI  - Fatal case of cerebral aspergillosis : a case report and literature review.
AB  - Cerebral aspergillosis is rare and usually misdiagnosed because its presentation
      is similar to that of a tumor. The correct diagnosis is usually made intra
      operatively. Cerebral abscess with fungal infection is extremely rare and few
      cases have been reported, but it carries a poor prognosis.A 73 year-old man
      presented with decreased visual acuity and paresis of the right cranial nerve
      III. Magnetic resonance imaging (MRI) revealed a mass in the right cavernous
      sinus, extened to the anterior crainial fossa and the superior orbital fissure.
      During surgery, a well encapsulated pus pocket was found, and histopathological
      examination of the mass resulted in the diagnosis of aspergillosis. Despite
      appropriate anti-fungal treatment, the patient eventually died from fatal
      cerebral ischemic change and severe brain swelling.The correct diagnosis of
      cerebral aspergillosis can only be achieved by histopathological examination
      because clinical and radiological findings including MRI are not specific.
      Surgical intervention and antifungal therapy should be considered the optimal
      treatment. Early diagnosis and aggressive antifungal treatment provide good
      results.

PMID- 23133738
TI  - Reverse latissimus dorsi muscle flap for an extensive soft tissue defect
      accompanied by infectious spondylitis.
AB  - Spinal infection is an inflammatory process around the vertebral body, and it can
      extend to the epidural space, posterior elements and paravertebral soft tissues.
      Infectious spondylitis is a rare infectious disorder, which is often associated
      with significant neurologic deficits and mortality. When an extensive soft tissue
      defect is accompanied by infectious spondylitis, effective infection control and
      proper coverage of soft tissue are directly connected to successful outcomes.
      However, it is not simple to choose the appropriate treatment methods for
      infectious spondylitis accompanied by a soft tissue defect. Herein, we report a
      case of severe infectious spondylitis that was accompanied by an extensive soft
      tissue defect which was closed with a reverse latissimus muscle flap after
      traumatic spinal epidural hemorrhage.

PMID- 23133739
TI  - Minimally invasive removal of an intradural cervical tumor : assessment of a
      combined split-spinous laminectomy and quadrant tube retractor system technique.
AB  - Conventional laminectomy is the most popular technique for the complete removal
      of intradural spinal tumors. In particular, the central portion intramedullary
      tumor and large intradural extramedullary tumor often require a total laminectomy
      for the midline myelotomy, sufficient decompression, and adequate visualization.
      However, this technique has the disadvantages of a wide incision, extensive
      periosteal muscle dissection, and bony structural injury. Recently, split-spinous
      laminectomy and tubular retractor systems were found to decrease postoperative
      muscle injuries, skin incision size and discomfort. The combined technique of
      split-spinous laminectomy, using a quadrant tube retractor system allows for an
      excellent exposure of the tumor with minimal trauma of the surrounding tissue. We
      propose that this technique offers possible advantages over the traditional open
      tumor removal of the intradural spinal cord tumors, which covers one or two
      cervical levels and requires a total laminectomy.

PMID- 23133740
TI  - Optimizing PK properties of cyclic peptides: the effect of side chain
      substitutions on permeability and clearance().
AB  - A series of cyclic peptides were designed and prepared to investigate the
      physicochemical properties that affect oral bioavailabilty of this chemotype in
      rats. In particular, the ionization state of the peptide was examined by the
      incorporation of naturally occurring amino acid residues that are charged in
      differing regions of the gut. In addition, data was generated in a variety of in
      vitro assays and the usefulness of this data in predicting the subsequent oral
      bioavailability observed in the rat is discussed.

PMID- 23133741
TI  - Clinical applications of the photopic negative response to optic nerve and
      retinal diseases.
AB  - The photopic negative response (PhNR) in response to a brief flash is a negative
      going wave following the b-wave of the cone electroretinogram (ERG) that is
      driven by retinal ganglion cells (RGCs). The function of RGCs is objectively
      evaluated by analysing the PhNR. We reviewed articles regarding clinical use of
      the PhNR. The PhNR was well correlated with the visual sensitivity obtained by
      standard automated perimetry and morphometric parameters of the inner retina and
      optic nerve head in optic nerve and retinal diseases. Moreover, combining the
      PhNR with focal or multifocal ERG techniques enables the objective assessment of
      local function of RGCs. The PhNR is therefore likely to become established as an
      objective functional test for optic nerve and retinal diseases involving RGC
      injury.

PMID- 23133742
TI  - Investigation of homocysteine-pathway-related variants in essential hypertension.
AB  - Hyperhomocysteinemia (hHcy) has been associated with an increased risk of
      cardiovascular disease and stroke. Essential hypertension (EH), a polygenic
      condition, has also been associated with increased risk of cardiovascular related
      disorders. To investigate the role of the homocysteine (Hcy) metabolism pathway
      in hypertension we conducted a case-control association study of Hcy pathway gene
      variants in a cohort of Caucasian hypertensives and age- and sex-matched
      normotensives. We genotyped two polymorphisms in the methylenetetrahydrofolate
      reductase gene (MTHFR C677T and MTHFR A1298C), one polymorphism in the methionine
      synthase reductase gene (MTRR A66G), and one polymorphism in the
      methylenetetrahydrofolate dehydrogenase 1 gene (MTHFD1 G1958A) and assessed their
      association with hypertension using chi-square analysis. We also performed a
      multifactor dimensionality reduction (MDR) analysis to investigate any potential
      epistatic interactions among the four polymorphisms and EH. None of the four
      polymorphisms was significantly associated with EH and although we found a
      moderate synergistic interaction between MTHFR A1298C and MTRR A66G, the
      association of the interaction model with EH was not statistically significant (P
      = 0.2367). Our findings therefore suggest no individual or interactive
      association between four prominent Hcy pathway markers and EH.

PMID- 23133743
TI  - The emerging role of heme oxygenase and its metabolites in the regulation of
      cardiovascular function.

PMID- 23133744
TI  - Prader-willi syndrome: clinical aspects.
AB  - Prader-Willi Syndrome (PWS) is a complex multisystem genetic disorder that shows
      great variability, with changing clinical features during a patient's life. The
      syndrome is due to the loss of expression of several genes encoded on the
      proximal long arm of chromosome 15 (15q11.2-q13). The complex phenotype is most
      probably caused by a hypothalamic dysfunction that is responsible for hormonal
      dysfunctions and for absence of the sense of satiety. For this reason a Prader
      Willi (PW) child develops hyperphagia during the initial stage of infancy that
      can lead to obesity and its complications. During infancy many PW child display a
      range of behavioural problems that become more noticeable in adolescence and
      adulthood and interfere mostly with quality of life. Early diagnosis of PWS is
      important for effective long-term management, and a precocious multidisciplinary
      approach is fundamental to improve quality of life, prevent complications, and
      prolong life expectancy.

PMID- 23133745
TI  - The impact of abdominal obesity status on cardiovascular response to the
      mediterranean diet.
AB  - We investigated the impact of abdominal obesity status on the cardiovascular
      response to a fully controlled 4-week isoenergetic Mediterranean diet (MedDiet).
      Thirty-eight abdominally obese individuals (waist circumference >102 cm in men
      and >88 cm in women) and thirty-one nonabdominally obese individuals were
      recruited and studied before and after the MedDiet. All analyses were adjusted
      for the slight decrease in body weight, which occurred during the MedDiet (mean:
      0.9 +/- 1.2 kg). A group by time interaction was noted for waist circumference (P
      = 0.02), abdominally obese subjects showing a significant decrease and
      nonabdominally obese subjects a nonsignificant increase (resp., -1.1 and +0.3%).
      The MedDiet resulted in decreases in total cholesterol, LDL-C, HDL-C,
      apolipoprotein B, A-1, and A-2, total cholesterol/HDL-C ratio, LDL-C/HDL-C ratio,
      and systolic and diastolic blood pressure (time effect: P < 0.05). For all
      variables related to glucose/insulin homeostasis, no change was observed except
      for a decrease in 2 h glucose concentrations (time effect: P = 0.03). No group by
      time interaction was observed in any of the metabolic variables studied. Results
      from our study suggest that the adoption of the MedDiet leads to beneficial
      metabolic effects, irrespective of the abdominal obesity status.

PMID- 23133746
TI  - Pulmonary complications in patients with severe brain injury.
AB  - Pulmonary complications are prevalent in the critically ill neurological
      population. Respiratory failure, pneumonia, acute lung injury and the acute
      respiratory distress syndrome (ALI/ARDS), pulmonary edema, pulmonary contusions
      and pneumo/hemothorax, and pulmonary embolism are frequently encountered in the
      setting of severe brain injury. Direct brain injury, depressed level of
      consciousness and inability to protect the airway, disruption of natural defense
      barriers, decreased mobility, and secondary neurological insults inherent to
      severe brain injury are the main cause of pulmonary complications in critically
      ill neurological patients. Prevention strategies and current and future therapies
      need to be implemented to avoid and treat the development of these life
      threatening medical complications.

PMID- 23133747
TI  - Bedside ultrasound in resuscitation and the rapid ultrasound in shock protocol.
AB  - Assessment of hemodynamic status in a shock state remains a challenging issue in
      Emergency Medicine and Critical Care. As the use of invasive hemodynamic
      monitoring declines, bedside-focused ultrasound has become a valuable tool in the
      evaluation and management of patients in shock. No longer a means to simply
      evaluate organ anatomy, ultrasound has expanded to become a rapid and noninvasive
      method for the assessment of patient physiology. Clinicians caring for critical
      patients should strongly consider integrating ultrasound into their resuscitation
      pathways.

PMID- 23133748
TI  - Evaluating Depression Care Management in a Community Setting: Main Outcomes for a
      Medicaid HMO Population with Multiple Medical and Psychiatric Comorbidities.
AB  - The authors describe the implementation of a depression care management (DCM)
      program at Colorado Access, a public sector health plan, and describe the
      program's clinical and system outcomes for members with chronic medical
      conditions. High medical risk, high cost Medicaid health plan members were
      identified and systematically screened for depression. A total of 370 members
      enrolled in the DCM program. Longitudinal analyses revealed significantly reduced
      depression severity scores at 3, 6, and 12 months after intervention as compared
      to baseline depression scores. At 12 months, 56% of enrollees in the DCM program
      had either a 50% reduction in PHQ-9 scores or a PHQ-9 score < 10. Longitudinal
      economic analyses comparing 12 months before and after intervention revealed a
      significant but modest increase in ER visits, outpatient office visits, and
      overall medical and pharmacy costs when adjusted for months enrolled in DCM.
      Limitations and recommendations for the integrated depression care management are
      discussed.

PMID- 23133749
TI  - The TNF-alpha -308 Promoter Gene Polymorphism and Chronic HBV Infection.
AB  - Background and Aims. TNF-alpha -308 allele promoter polymorphism has been known
      to be a potential prognostic factor in patients with chronic HBV infection. We
      tried to determine how TNF-alpha -308 allele promoter polymorphism would affect
      the prognosis in patients with chronic HBV infection. Methods. We searched
      MEDLINE, EMBASE, and reference lists of relevant review articles related to the
      association between "TNF-alpha G-308A promoter polymorphism" with "chronic HBV
      infection". We only focused on searching -308 locus in published studies. We
      reviewed 21 original articles about TNF-alpha -308 allele polymorphism and its
      effect on prognosis in patients with chronic HBV infection and discussed the
      results. Results. conflicting results were observed. The results were divided
      into 3 groups including neutral, negative, and positive associations between TNF
      alpha -308 allele polymorphism and prognosis in patients with chronic HBV
      infection. We summarized the primary data as a table. Conclusions. Authors
      concluded that although there is an upward trend in evidence to claim that there
      is a positive relation between TNF-alpha G-308A promoter polymorphisms and
      resolution of chronic HBV infection, due to many biases and limitations observed
      in reviewed studies, an organized well-designed study is needed for clarifying
      the real association.

PMID- 23133750
TI  - The job satisfaction of finnish nursing staff: the development of a job
      satisfaction scale and survey results.
AB  - This paper describes the development of the Kuopio University Hospital Job
      Satisfaction Scale (KUHJSS) and the results of the survey. The scale was
      developed through a systematic literature review, and its validity and
      reliability were assessed using several psychometric properties including expert
      evaluation (n = 5), a pilot survey (n = 172), and exploratory factor analysis.
      The final version of KUHJSS included 37 items. A large sample psychometric
      evaluation was made by nursing staff (n = 2708). The exploratory factor analysis
      revealed seven factors with modest internal consistency (0.64-0.92). The staff
      reported relatively high job satisfaction. The greatest satisfaction was derived
      from motivating factors associated with the work; the least, from the job's
      demands. Respondents who considered their working units to provide an excellent
      quality of care reported the highest job satisfaction in every subarea (P <
      .0001). The KUHJSS proved to be a reliable and valid tool for measuring job
      satisfaction in hospital care.

PMID- 23133751
TI  - Pathological role of interleukin-6 in psoriatic arthritis.
AB  - Psoriatic arthritis (PsA) is a clinical manifestation of psoriatic disease.
      Although the pathogenesis of PsA remains unknown, PsA can be managed by
      treatments similar to those used for rheumatoid arthritis (RA). Because
      interleukin-(IL-) 6 has been suggested to have a pathogenic role in PsA, a
      humanized anti-IL-6 receptor antibody tocilizumab treatment for PsA was recently
      tried. However, the efficacy of tocilizumab for PsA was not favorable. This
      suggests that the pathogenic roles of IL-6 in PsA and RA are different. In RA,
      tumor necrosis factor (TNF) primarily contributes to the arthritis effector phase
      and IL-6 contributes to the arthritis priming phase. In PsA, the TNF-related
      effector phase is similar to that in RA, but the IL-6-related priming phase might
      not be critical. This paper discusses the role of IL-6 in PsA.

PMID- 23133753
TI  - Statins for renal patients: a fiddler on the roof?
AB  - Atherosclerotic cardiovascular disease is the main cause of morbidity and
      mortality in chronic kidney disease patients. There is a raft of evidence showing
      that in the general population dyslipidaemia is associated with an increased risk
      of cardiovascular events, as well as with a greater prevalence of chronic kidney
      disease. Consequently, the use of statins in the general population with
      dyslipidaemia is not controversial. Nevertheless, the benefits of statins in
      patients with chronic kidney disease are more elusive. The authors review the
      possible effects of statins on the progression of renal disease and
      cardiovascular events in chronic kidney disease patients.

PMID- 23133754
TI  - "Calcitriol" is not synonymous with "vitamin d".

PMID- 23133752
TI  - The role of different subsets of regulatory T cells in immunopathogenesis of
      rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a common autoimmune disease and a systemic
      inflammatory disease which is characterized by chronic joint inflammation and
      variable degrees of bone and cartilage erosion and hyperplasia of synovial
      tissues. Considering the role of autoreactive T cells (particularly Th1 and Th17
      cells) in pathophysiology of RA, it might be assumed that the regulatory T cells
      (Tregs) will be able to control the initiation and progression of disease. The
      frequency, function, and properties of various subsets of Tregs including natural
      Tregs (nTregs), IL-10-producing type 1 Tregs (Tr1 cells), TGF-beta-producing Th3
      cells, CD8(+) Tregs, and NKT regulatory cells have been investigated in various
      studies associated with RA and collagen-induced arthritis (CIA) as experimental
      model of this disease. In this paper, we intend to submit the comprehensive
      information about the immunobiology of various subsets of Tregs and their roles
      and function in immunopathophysiology of RA and its animal model, CIA.

PMID- 23133755
TI  - Differential effects of chronic pulsatile versus chronic constant maternal
      hyperglycemia on fetal pancreatic beta-cells.
AB  - Constant maternal hyperglycemia limits, while pulsatile maternal hyperglycemia
      may enhance, fetal glucose-stimulated insulin secretion (GSIS) in sheep. However,
      the impact of such different patterns of hyperglycemia on the development of the
      fetal beta-cell is unknown. We measured the impact of one week of chronic
      constant hyperglycemia (CHG, n = 6) versus pulsatile hyperglycemia (PHG, n = 5)
      versus controls (n = 7) on the percentage of the fetal pancreas staining for
      insulin (beta-cell area), mitotic and apoptotic indices and size of fetal beta
      cells, and fetal insulin secretion in sheep. Baseline insulin concentrations were
      higher in CHG fetuses (P < 0.05) compared to controls and PHG. GSIS was lower in
      the CHG group (P < 0.005) compared to controls and PHG. PHG beta-cell area was
      increased 50% (P < 0.05) compared to controls and CHG. CHG beta-cell apoptosis
      was increased over 400% (P < 0.05) compared to controls and PHG. These results
      indicate that late gestation constant maternal hyperglycemia leads to significant
      beta-cell toxicity (increased apoptosis and decreased GSIS). Furthermore,
      pulsatile maternal hyperglycemia increases pancreatic beta-cell area but did not
      increase GSIS, indicating decreased beta-cell responsiveness. These findings
      demonstrate differential effects that the pattern of maternal hyperglycemia has
      on fetal pancreatic beta-cell development, which might contribute to later life
      limitation in insulin secretion.

PMID- 23133757
TI  - ABO Blood Groups and Cardiovascular Diseases.
AB  - ABO blood groups have been associated with various disease phenotypes,
      particularly cardiovascular diseases. Cardiovascular diseases are the most common
      causes of death in developed countries and their prevalence rate is rapidly
      growing in developing countries. There have been substantial historical
      associations between non-O blood group status and an increase in some
      cardiovascular disorders. Recent GWASs have identified ABO as a locus for
      thrombosis, myocardial infarction, and multiple cardiovascular risk biomarkers,
      refocusing attention on mechanisms and potential for clinical advances. As we
      highlight in this paper, more recent work is beginning to probe the molecular
      basis of the disease associations observed in these observational studies.
      Advances in our understanding of the physiologic importance of various
      endothelial and platelet-derived circulating glycoproteins are elucidating the
      mechanisms through which the ABO blood group may determine overall cardiovascular
      disease risk. The role of blood group antigens in the pathogenesis of various
      cardiovascular disorders remains a fascinating subject with potential to lead to
      novel therapeutics and prognostics and to reduce the global burden of
      cardiovascular diseases.

PMID- 23133756
TI  - Blood flow restricted exercise and vascular function.
AB  - It is established that regular aerobic training improves vascular function, for
      example, endothelium-dependent vasodilatation and arterial stiffness or
      compliance and thereby constitutes a preventative measure against cardiovascular
      disease. In contrast, high-intensity resistance training impairs vascular
      function, while the influence of moderate-intensity resistance training on
      vascular function is still controversial. However, aerobic training is
      insufficient to inhibit loss in muscular strength with advancing age; thus,
      resistance training is recommended to prevent sarcopenia. Recently, several lines
      of study have provided compelling data showing that exercise and training with
      blood flow restriction (BFR) leads to muscle hypertrophy and strength increase.
      As such, BFR training might be a novel means of overcoming the contradiction
      between aerobic and high-intensity resistance training. Although it is not enough
      evidence to obtain consensus about impact of BFR training on vascular function,
      available evidences suggested that BFR training did not change coagulation
      factors and arterial compliance though with inconsistence results in endothelial
      function. This paper is a review of the literature on the impact of BFR exercise
      and training on vascular function, such as endothelial function, arterial
      compliance, or other potential factors in comparison with those of aerobic and
      resistance training.

PMID- 23133758
TI  - Neurotropic melanoma: the management of localised disease.
AB  - Neurotropic melanoma is a rare subtype of cutaneous malignant melanoma. Compared
      with conventional melanoma, it is more locally aggressive with an increased
      tendency for local recurrence but less likely for nodal or distant metastases.
      These tumours can be a diagnostic dilemma with a variety of morphological,
      histopathological, and immunophenotypical expressions. The often amelanotic,
      benign appearance may lead to treatment issues such as late presentation,
      diagnostic delay, misdiagnosis, insufficient surgical margins, and recurrence
      with resulting poor outcome. The neurotropic nature of the disease and prevalence
      in the head and neck region can result in perineural and neural invasion along
      named large nerves into the brain with resulting neuropathies. Wide local
      excision with adjuvant radiotherapy where indicated remains the current practice
      for treatment with chemotherapy predominately being reserved as a salvage
      treatment for patients with disseminated disease.

PMID- 23133759
TI  - The MAPK MEK1/2-ERK1/2 Pathway and Its Implication in Hepatocyte Cell Cycle
      Control.
AB  - Primary cultures of hepatocytes are powerful models in studying the sequence of
      events that are necessary for cell progression from a G0-like state to S phase.
      The models mimic the physiological process of hepatic regeneration after liver
      injury or partial hepatectomy. Many reports suggest that the mitogen-activated
      protein kinase (MAPK) ERK1/2 can support hepatocyte proliferation in vitro and in
      vivo and the MEK/ERK cascade acts as an essential element in hepatocyte responses
      induced by the EGF. Moreover, its disregulation has been associated with the
      promotion of tumor cell growth of a variety of tumors, including hepatocellular
      carcinoma. Whereas the strict specificity of action of ERK1 and ERK2 is still
      debated, the MAPKs may have specific biological functions under certain contexts
      and according to the differentiation status of the cells, notably hepatocytes. In
      this paper, we will focus on MEK1/2-ERK1/2 activations and roles in normal rodent
      hepatocytes in vitro and in vivo after partial hepatectomy and in human
      hepatocarcinoma cells. The possible specificity of ERK1 and ERK2 in normal and
      transformed hepatocyte will be discussed in regard to other differentiated and
      undifferentiated cellular models.

PMID- 23133760
TI  - A current review of the diagnostic and treatment strategies of hepatic
      encephalopathy.
AB  - Hepatic encephalopathy (HE) is a serious and potentially fatal complication in
      patients with cirrhotic liver disease. It is a spectrum ranging from minimal
      hepatic encephalopathy (MHE) without recognizable clinical symptoms or signs, to
      overt HE with risk of cerebral edema and death. HE results in diminished quality
      of life and survival. The broad range of neuropsychiatric manifestations reflects
      the range of pathophysiological mechanisms and impairment in neurotransmission
      that are purported to cause HE including hyperammonemia, astrocyte swelling,
      intra-astrocytic glutamine, upregulation of 18-kDa translocator protein (TSPO)
      (formerly known as peripheral benzodiazepine receptor or PBTR), and manganese.
      There is a myriad of diagnostic tools including simple bedside clinical
      assessment, and more complex neuropsychological batteries and neurophysiological
      tests available today. Current treatment strategies are directed at reducing
      ammonia, with newer agents showing some early promise. This paper describes the
      pathophysiology of the disease and summarises current diagnostic and treatment
      therapies available.

PMID- 23133761
TI  - Unusual presentation of cystic papillary thyroid carcinoma.
AB  - Papillary thyroid carcinoma is the most common thyroid malignancy, accounting for
      80% of all thyroid cancers. The most common presentation of thyroid cancer is an
      asymptomatic thyroid mass or a nodule. Usually as thyroid enlarges, it extends in
      to mediastinum. Papillary thyroid carcinoma presentation as multiple true cystic
      swelling extending from neck to anterior chest wall in subcutaneous plane is not
      present in the literature. We present a rare case of cystic papillary thyroid
      carcinoma which is presented as subcutaneous swelling with sinus formation.

PMID- 23133762
TI  - Amyloid accumulation in the toxic nodule of the thyroid gland in a patient with
      end stage renal failure.
AB  - Amyloidosis is characterized by accumulation of amorphous, proteinaceous material
      in various organs and tissues of the body. Amyloid may accumulate in the thyroid
      gland in cases of medullary thyroid carcinoma and systemic amyloidosis. Amyloid
      accumulates extracellularly in the thyroid parenchyma and disrupts the normal
      follicular patterns. Most of the cases reported up to now were clinically
      euthyroid, but many presentation forms and overlaps have been reported. Herein we
      present a patient with toxic nodular goiter with amyloid deposition in the toxic
      nodule as well as the remaining thyroid tissue.

PMID- 23133763
TI  - Prenatal diagnosis and postnatal followup of partial trisomy 13q and partial
      monosomy 10p: a case report and review of the literature.
AB  - We report prenatal diagnosis and postnatal findings of a fetus with partial
      trisomy of 13q21.33-qter and partial monosomy of 10p15.3-pter. The mother is a
      known carrier of a balanced translocation, t(10;13)(p15.3;q21.33), ascertained by
      history of one miscarriage and two neonatal deaths. The fetal karyotyping on
      cultured amniocytes showed 46,XX,der(10)t(10;13)(p15.3;q21.33). Oligonucleotide
      array comparative genomic hybridization (aCGH) defined a 2.339 Mb distal deletion
      at 10p15.3 (chr10:126,161-2,465,089) and a 46.344 Mb duplication of 13q21.33-q34
      (chr13:67,779,708-114,123,540). Ultrasound examination showed polydactyly and
      polyhydramnios in the fetus. After genetic counseling, the mother decided to
      continue the pregnancy, and follow-up ultrasound monitoring found no further
      abnormalities. A girl was delivered at 37(+6) weeks of gestation and was
      transferred to the intensive care unit for intermittent convulsions within 26
      hours. She was diagnosed with neonatal hypoxic ischemic encephalopathy and
      experienced several episodes of apnea in the following month. Her birth weight
      was 2900 g (10-25th centile) and at five months was 5500 g (5-10th centile). She
      had dysmorphic features and mild psychomotor retardation. A review of the
      literature found three previously reported cases with similar compound 10p/13q
      abnormalities. We discuss a two-step approach to assess fetal viability and
      phenotype using genomic information from partial trisomy and monosomy.

PMID- 23133764
TI  - A tragical paediatric case history of intraorbital and intracranial epithelioid
      hemangioendothelioma.
AB  - Epithelioid hemangioendothelioma (EHE) is a rare tumor of intermediate
      malignancy. We report a case of intracranial and intraorbitar EHE. A 3-year-old
      girl presented with a 3-month history of progressive left exophthalmia.
      Neuroradiologic imaging (CT scan and MRI) showed an intraorbitar process with an
      intense enhancement extending to temporal fossa, ethmoidal bone, nasal fossa,
      maxillary sinus, and cavernous sinus. The angiogram was normal. The tumor was
      operated through subfrontal approach but only a partial resection was performed.
      The histological diagnosis was epithelioid hemangioendothelioma. The patient was
      neurologically intact 2 months after surgery without exophtalmia. However 4
      months after surgery he displayed a fall of the right eye vision with intense
      headache. Control CT scan showed persistence of important tumoral residue.
      Epithelioid hemangioendothelioma is a hemorrhagic tumor. Total removal must be
      possible. Otherwise, we recommend a complementary chemoradiotherapy and close
      followup. We propose this interesting case history of a tragical evolution of EHE
      in contradiction with what has already been reported.

PMID- 23133765
TI  - Imaging of postpartum ovarian vein thrombosis.
AB  - Postpartum ovarian vein thrombosis (OVT) is a rare but serious complication.
      Clinical findings of OVT are nonspecific. Postpartum OVT, which is a clinically
      difficultly diagnosed entity, must be thought of in differential diagnosis in
      cases of postpartum acute abdomen. OVT can be accurately diagnosed by appropriate
      noninvasive radiologic modalities to start early therapy with anticoagulants and
      intravenous antibiotics. In this paper, we review the imaging findings of a case
      with postpartum ovarian vein thrombosis that had been followed up for 6 months by
      ultrasonography (US), color Doppler US, computed tomography (CT), and magnetic
      resonance imaging (MRI).

PMID- 23133766
TI  - Sister Mary Joseph's Nodule as a First Manifestation of Primary Peritoneal
      Cancer.
AB  - Sister Mary Joseph's nodule metastasis is a rather rare finding. The primary
      malignancy in women is usually ovarian, endometrial, gastric, or pancreatobiliary
      tree cancer. We present a case of an 87-year-old patient with Sister Mary
      Joseph's nodule metastasis caused by a primary peritoneal malignancy. Through a
      literature search, we also discuss the pathophysiology, diagnostic approach,
      management, and prognosis of such a condition.

PMID- 23133767
TI  - Sudden death of a pregnant woman in third trimester with no risk factor.
AB  - Acute myocardial infarction in pregnancy is rare and life-threatening for both
      the mother and the fetus. We present the case of a 31-year-old previously healthy
      woman with no risk factors at 32 weeks of gestation who applied with vomiting,
      dyspnea and orthopnea. A respiratory arrest developed followed by loss of the
      fetal viability, cardiac arrest, and failure of resuscitation. We aim to raise
      awareness about the clinical approach to pregnant patients who are to be
      considered with a broad spectrum of differential diagnosis.

PMID- 23133768
TI  - Nonmetastatic Ewing's Sarcoma of the Lumbar Spine in an Adult Patient.
AB  - Although the spine is frequently involved in metastatic Ewing's sarcoma, primary
      involvement of the spine, beside sacrum, is much less frequent, especially in
      adult patients. Because of the low incidence of these tumors, there are currently
      no clinical guidelines outlining their management and a multitude of therapeutic
      strategies have been employed with varying success. The definitive management of
      Ewing's sarcoma of the spine, as in other locations, could include the
      combination of three main modalities: aggressive surgery, radiotherapy, and
      combined chemotherapy. Whenever possible, en bloc spondylectomy or extralesional
      resection is preferable, providing a better oncological result with a longer
      survival and a better preservation of the spine biomechanics. This is the lesson
      we learned about the case, we present here, of nonmetastatic lumbar localization
      by Ewing's sarcoma in as adult patient.

PMID- 23133769
TI  - Lymphoepithelioma-like carcinoma of the skin treated with wide local excision and
      chemoradiation therapy: a case report and review of the literature.
AB  - Lymphoepithelioma-like carcinoma of the skin (LELCS) is a rare cutaneous neoplasm
      microscopically similar to undifferentiated nasopharyngeal carcinoma. It is
      typically nonaggressive and is treated with wide local excision. However, we
      present a case of a patient with a regional recurrence and more aggressive LELCS
      with perineural invasion and positive margins for which he was treated with wide
      local excision followed by chemoradiation. We discuss the use of chemoradiation
      for this patient and review the literature, specifically pertaining to treatment
      of more aggressive cases of LELCS.

PMID- 23133770
TI  - Metastasis of renal cell carcinoma to the buccal mucosa 19 years after radical
      nephrectomy.
AB  - Renal cell carcinoma (RCC) has high metastatic potential, which requires early
      diagnosis to optimize the chance of cure. Metastasis of RCC to the head and neck
      region is less common and metastasis to the buccal mucosa is extremely rare. This
      phenomenon occurs mostly in patients with generalized dissemination, especially
      with lung metastases. In this article we report a case of buccal mucosa
      metastasis from RCC in a 65-year-old man who presented 19 years after undergoing
      a left radical nephrectomy for clear cell RCC. Surgical excision of the buccal
      lesion was performed without evidence of recurrence or new metastatic lesions
      after 6 years of followup. To our knowledge, this is the first case of metastasis
      to the buccal mucosa from a RCC reported in the literature.

PMID- 23133771
TI  - Bilateral choroidal metastases as presentation of dissemination of cutaneous
      malignant melanoma.
AB  - Case Report. A 47-year-old man presented with blurred vision in the right eye.
      Ophthalmoscopic examination showed several placoid, pigmented lesions in the
      posterior pole and midperiphery of the retina of both eyes. Results. Patient
      referred a cutaneous malignant melanoma on the back skin removed 6 years ago. A
      systemic workup revealed multiple metastases in liver and spleen. After an
      exhaustive study we concluded that it was a dissemination of a cutaneous
      malignant melanoma with bilateral choroidal metastases, liver and spleen
      metastases. The patient obtained clinical ocular improvement after palliative
      chemotherapy, although he died in the following months. Pathological examination
      of the lesions confirmed the diagnosis of choroidal metastases from a malignant
      cutaneous melanoma. Conclusions. Monitoring patients who have had cutaneous
      malignant melanoma is very important, since melanoma metastases may occur even
      many years after the diagnosis of the primary tumor. Choroidal metastases from
      cutaneous melanoma are uncommon but we should be aware because their appearance
      worsens prognosis.

PMID- 23133772
TI  - A Rare Presentation of Concurrent Scedosporium apiospermum and Madurella grisea
      Eumycetoma in an Immunocompetent Host.
AB  - Mycetoma is a disfiguring, chronic granulomatous infection which affects the skin
      and the underlying subcutaneous tissue. We present an atypical case of recurrent
      mycetoma without ulceration, in a 35-year-old immunocompetent male caused by
      Scedosporium apiospermum sensu stricto and Madurella grisea, occurring at two
      separate anatomical sites.

PMID- 23133773
TI  - Primary renal epithelioid hemangioendothelioma.
AB  - Epithelioid hemangioendothelioma is a rare vascular tumor with intermediate
      biologic behavior and metastatic potential. Primary renal epithelioid
      hemangioendothelioma is extremely rare and we present the second report of this
      rare tumor in an interesting clinical scenario. A 59-year-old male with
      established history of widely metastatic high grade esophageal adenocarcinoma was
      found to have an isolated renal nodule on a followup computed tomography (CT)
      scan. Surgical excision, with the suspicion of metastatic carcinoma, and
      subsequent pathologic examination revealed an epithelioid hemangioendothelioma.
      The various differential diagnoses and use of morphological clues and
      immunohistochemistry are discussed.

PMID- 23133774
TI  - Plasmacytoid melanoma of the urinary bladder and lymph nodes with
      immunohistochemical expression of plasma cell markers revealing primary
      esophageal melanoma.
AB  - Plasmacytoid variant of melanoma is reported in only rare cases. We present the
      case of a 54-years-old man admitted for enlarged lymph nodes in the lumbar
      region. Initial diagnosis of plasmablastic lymphoma/plasma cell myeloma was
      considered. At our institute, a bladder polyp was removed. Microscopic exam
      demonstrated dense plasmacytoid cells infiltration with pigment deposits.
      Immunohistochemical study showed strong expression of HMB45, Melan A, and
      vimentin. There was focal positivity with S100 protein and CD138/syndecan-1. The
      diagnosis of metastatic plasmacytoid melanoma was finally established. Clinical
      exam revealed an esophageal melanoma with melanosis supporting its primary
      location. Although rarely, melanoma especially plasmacytoid variant may express
      plasma cell markers which may lead to erroneous diagnosis of plasma cell
      proliferation. Careful morphological examination for melanin pigment and the use
      of panel of melanocytic markers are helpful for diagnosis.

PMID- 23133775
TI  - Male Child with Van Wyk-Grumbach's Syndrome and Other Complications of Long
      Standing Primary Hypothyroidism: A Case Report.
AB  - Primary hypothyroidism in the juvenile population generally leads to retardation
      of linear growth and delay or even arrest of puberty. However, in rare
      conditions, children with long-standing hypothyroidism present with signs of Van
      Wyk-Grumbach's syndrome (VWGS) which include juvenile hypothyroidism, delayed
      bone age, and pseudoprecocious puberty. We report a rare case of prepubertal male
      child from Asian origin, presented with long-standing untreated hypothyroidism
      complicated with VWGS and other complications including obesity, short stature,
      hepatomegaly, asymptomatic mild pericardial effusion, and pituitary hyperplasia.

PMID- 23133776
TI  - Mycophenolate mofetil-related enterocolitis and weight loss: a pediatric case
      series.
AB  - Mycophenolate mofetil (MMF) is an immunosuppressive medication utilized in the
      management of both autoimmune and solid organ transplant patients. Diarrhea is a
      common gastrointestinal side effect of MMF, but more severe forms of GI symptoms
      are described in renal transplant patients with a distinct pattern of
      histopathologic change, similar to graft-versus-host disease or Crohn's disease.
      This rare entity, commonly referred to as "MMF-related enterocolitis," has been
      described in adult patients, mostly in renal transplant patients, and in only two
      pediatric renal transplant patients. In previously reported cases, symptoms and
      abnormal histopathology improve with dose reduction of MMF. We describe a series
      of three pediatric patients with varied underlying disease process who presented
      with severe diarrhea and histopathologic findings characteristic of MMF-related
      enterocolitis, who share a novel finding of weight loss as a complication of MMF
      related enterocolitis in pediatric patients.

PMID- 23133777
TI  - Chronic thromboembolic pulmonary hypertension: treat the patient not the
      haemodynamics.
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) is a disabling condition
      that is being increasingly recognised. It is unique as a cause of pulmonary
      hypertension in that it is surgically curable. We wish to highlight the
      importance of recognition and early referral of any patient who may have CTEPH
      even in the absence of resting pulmonary hypertension as excellent results can be
      achieved by restoring pulmonary vascular anatomy, reducing exercise-induced
      pulmonary hypertension, and reducing dead-space ventilation. We present a case
      that illustrates these points and discuss our experience as a referral centre for
      CTEPH.

PMID- 23133778
TI  - A Case of Follicular Bronchiolitis as the Histological Counterpart to Nodular
      Opacities in Bronchiectatic Mycobacterium avium Complex Disease.
AB  - Here we report the case of a 72-year-old woman with nodular bronchiectatic
      Mycobacterium avium complex (MAC) disease. Chest computed tomography on admission
      revealed multiple micronodular and branching opacities in both lobes with
      segmental distribution; bronchiectasis and bronchial wall thickening were
      observed in the middle lobe and lingula. The patient consented to and underwent
      thoracoscopic lung biopsy; epithelioid granulomas were occasionally observed, but
      follicular bronchiolitis was widespread. While bronchial lesions from
      nontuberculous mycobacterial infection generally present as epitheliod
      granulomas, the present case suggests that follicular bronchiolitis can also be a
      histological counterpart to nodular opacities in nodular bronchiectatic MAC
      disease.

PMID- 23133779
TI  - Bortezomib-induced bronchiolitis obliterans organizing pneumonia.
AB  - Introduction. Bortezomib is a proteasome inhibitor indicated for the treatment of
      multiple myeloma patients. The most frequent side effects are gastrointestinal
      and neurological. Serious pulmonary complications have been described rarely.
      Observation. This case involves a 74-year-old man suffering from IgG Kappa
      myeloma treated with bortezomib, melphalan, and dexamethasone. After
      administering chemotherapy, the patient developed an acute respiratory distress
      syndrome (ARDS). A surgical pulmonary biopsy proved the existence of
      bronchiolitis obliterans organizing pneumonia (BOOP) lesions. Systemic
      corticotherapy led to a rapid improvement in the patient's condition. Conclusion.
      This is the first reported histologically confirmed case of bortezomid-induced
      BOOP. Faced with severe respiratory symptoms in the absence of other etiologies,
      complications due to bortezomid treatment should be evoked and corticotherapy
      considered.

PMID- 23133780
TI  - Idiopathic clubbing confined to lower limb digits and idiopathic pulmonary
      fibrosis: an unusual association.
AB  - A 62-year-old housewife presented to the chest outpatient department with a
      history of exertional breathlessness of four-month duration. On general physical
      examination, clubbing of toes was present with sparing of fingers. Chest
      examination revealed bilateral basal end inspiratory fine crepitations. A
      diagnosis of idiopathic pulmonary fibrosis was made on the basis of clinical,
      spirometric, and high-resolution computed tomography findings. Extensive
      evaluation could not reveal any cause for the differential clubbing. The unusual
      distribution of clubbing in a clinical condition, such as idiopathic pulmonary
      fibrosis, where generalized clubbing is expected can lead to a diagnostic
      confusion. This can lead to a further burden of investigations on the patient as
      clubbing being a significant finding cannot be ignored.

PMID- 23133781
TI  - Massive hemoptysis in a case of intralobar pulmonary sequestration associated
      with pulmonary hypoplasia and meandering right pulmonary vein: diagnosis and
      management.
AB  - Pulmonary sequestration is a congenital malformation characterized by focal area
      of dysplastic lung tissue that lacks normal communication with tracheobronchial
      tree and receives blood supply from systemic arteries. Surgical resection has
      been the conventional method of treatment of pulmonary sequestration. In recent
      years transarterial embolization of the anomalous systemic arteries has emerged
      as a suitable alternative to surgery. In this paper, we describe transarterial
      coil embolization for control of massive life-threatening hemoptysis in a rare
      case of intralobar sequestration in right lung associated with ipsilateral
      pulmonary hypoplasia and meandering right inferior pulmonary vein. A 3-year
      follow-up computed tomographic (CT) angiography revealed complete regression of
      the sequestration along with altered pulmonary arterial contour. To the best of
      our knowledge, transarterial coil embolization for control of massive life
      threatening hemoptysis in such a complex pulmonary anomaly has not yet been
      reported.

PMID- 23133782
TI  - Medulloblastoma with excessive nodularity: radiographic features and pathologic
      correlate.
AB  - Medulloblastoma with extensive nodularity is a rare subtype of the most common
      malignant childhood brain tumor and has been associated with more favorable
      prognosis. The authors report the case of a 10-month-old girl with a posterior
      fossa tumor of excessive nodularity with decreased diffusivity on diffusion
      weighted magnetic resonance imaging sequences and robust grape-like
      postgadolinium contrast enhancing features. The unique neuroradiographic features
      were confirmed by histopathology and a diagnosis of medulloblastoma with
      extensive nodularity was made. This case highlights the importance of recognizing
      this unique medulloblastoma subtype preoperatively, as the more favorable outcome
      may preclude less aggressive medical management.

PMID- 23133783
TI  - Laparoscopic navigated liver resection: technical aspects and clinical practice
      in benign liver tumors.
AB  - Laparoscopic liver resection has been performed mostly in centers with an
      extended expertise in both hepatobiliary and laparoscopic surgery and only in
      highly selected patients. In order to overcome the obstacles of this technique
      through improved intraoperative visualization we developed a laparoscopic
      navigation system (LapAssistent) to register pre-operatively reconstructed three
      dimensional CT or MRI scans within the intra-operative field. After experimental
      development of the navigation system, we commenced with the clinical use of
      navigation-assisted laparoscopic liver surgery in January 2010. In this paper we
      report the technical aspects of the navigation system and the clinical use in one
      patient with a large benign adenoma. Preoperative planning data were calculated
      by Fraunhofer MeVis Bremen, Germany. After calibration of the system including
      camera, laparoscopic instruments, and the intraoperative ultrasound scanner we
      registered the surface of the liver. Applying the navigated ultrasound the
      preoperatively planned resection plane was then overlain with the patient's
      liver. The laparoscopic navigation system could be used under sterile conditions
      and it was possible to register and visualize the preoperatively planned
      resection plane. These first results now have to be validated and certified in a
      larger patient collective. A nationwide prospective multicenter study (ProNavic
      I) has been conducted and launched.

PMID- 23133784
TI  - Gossypiboma causing mechanical intestinal obstruction: a case report.
AB  - Introduction. Gossypiboma (GP) is a term used to express the mass resulting from
      forgotten cotton sponge in operations. Rarely, a transmural migration may occur
      into the gastrointestinal lumen without creating any defect by GP. Laparotomy or
      endoscopic removal may be required, by the way it can be taken out of the body
      itself by intestinal ways. In this study, we reported a case of mechanical
      intestinal obstruction causing GP. Case. The fifty-one-year-old female patient
      admitted to the emergency department with the complaints of mechanical intestinal
      obstruction and had a history of open cholecystectomy 20 years ago. There were
      the findings of intestinal obstruction in abdominal plain radiography and
      computerized tomography. The sponge that obstructed the lumen completely 40 cm
      proximal to the ileocecal valve was identified in the laparotomy with the
      diagnosis of brid ileus. The small intestine was closed over double-fold after
      removal of sponge. Transmural migration of abdominal-remained sponge was thought
      to be occurred without creating a defect after cholecystectomy. Postoperatively,
      the patient was discharged without having any problems at 4th day of
      hospitalization. Conclusion. Although it is a rare situation in routine clinical
      practice, GP should be considered as a differential diagnosis in the patients who
      had a diagnosis of mechanical intestinal obstruction, and laparotomy was applied
      before. As GP may lead to situations which cause mortality, all precautions
      should be taken to prevent it.

PMID- 23133785
TI  - Metastatic transitional cell carcinoma of the bladder to the testis: a case
      report.
AB  - An 84-year-old gentleman presented with onset of gross hematuria in September
      2010. Follow-up investigations revealed T1 superficially invasive, poorly
      differentiated, papillary urothelial carcinoma. He subsequently had GreenLight
      laser for BPH and bladder neck contracture on two occasions. He developed a right
      hydrocele 16 months after initial presentation and during his hydrocelectomy, a
      rock-hard right epididymis and testicle were discovered. Pathology revealed
      metastatic urothelial carcinoma replacing nearly the entire testis with
      lymphovascular invasion.

PMID- 23133786
TI  - Idiopathic, serial coronary vessels dissection in a young woman with
      psychological stress: a case report and review of the literature.
AB  - Spontaneous coronary artery dissection (SCAD) is a very rare disease, associated
      with high mortality rate, whose etiology and pathogenesis are poorly understood.
      Its sporadic nature and the varied angiographic extent make firm recommendations
      regarding revascularization impossible. The case described is that of a young,
      otherwise healthy woman, without a known underlying condition which may lead to
      SCAD, but with a history of intense psychological stress. We managed the patient
      with a conservative approach based on watchful waiting, medical therapy, and
      plain old balloon angioplasty (POBA) with low inflation atmospheres.

PMID- 23133787
TI  - Pregnancy complicated with severe recurrent aortic coarctation: a case report.
AB  - A 23-year-old primigravida was referred to our clinic for evaluation of high
      blood pressure (BP) in her 16th week of gestation. She had an operation to repair
      congenital aortic coarctation and patent ductus arteriosus 8 years ago. On
      physical examination the blood pressure in upper extremity was 155/95 and in
      lower extremity was 90/55 mmHg, and heart rate was 93 beats/min. Transthoracic
      echocardiography showed narrowing of the descending aorta, the diameter of the
      aortic arch was 10.60 mm and an echocardiographic gradient was 96 mmHg. During
      the pregnancy (from 16 weeks to 38 weeks) BP was regulated with metoprolol.
      Cesarean section delivery was applied at 38 weeks of gestation. There was no
      complication in postpartum period. Spinal anesthesia application was used for
      caesarean section intervention and healthy female baby was delivered with the
      APGAR scores of 10/10. Herein the diagnosis of aortic coarctation is reviewed and
      the management when found during pregnancy is discussed.

PMID- 23133789
TI  - Confirmatory factor analysis of the motor unified Parkinson's disease rating
      scale.
AB  - The motor examination section of the unified Parkinson's disease rating scale
      (UPDRS) is widely used in research but few studies have examined whether
      subscales exist that tap relatively distinct motor abnormalities. We analyzed
      data from 193 persons enrolled in a population-based study in Central California.
      Patients were examined after overnight PD medication washout ("OFF" state) and
      approximately one hour after taking medication ("ON" state). We performed
      confirmatory factor analysis of the UPDRS for OFF and ON state examinations;
      correlations, reliability, and relative validity of resulting subscales were
      evaluated. A model with five factors (gait/posture, tremor, rigidity,
      bradykinesia affecting the left extremities, bradykinesia affecting the right
      extremities) fit the data well, with similar results for OFF and ON states.
      Internal consistency reliability coefficients were 0.90 or higher for all
      subscales. The gait/posture subscale most strongly discriminated across levels of
      patient reported PD symptom severity and of how PD affects them on a daily basis.
      Compared to the right sided bradykinesia subscale, the left sided bradykinesia
      subscale had higher discrimination across levels of self-reported PD symptom
      severity and functional impairment. This supports motor UPDRS containing multiple
      subscales that can be analyzed separately and provide information distinct from
      the total score that may be useful in clinical studies.

PMID- 23133788
TI  - Protein clearance mechanisms of alpha-synuclein and amyloid-Beta in lewy body
      disorders.
AB  - Protein clearance is critical for the maintenance of the integrity of neuronal
      cells, and there is accumulating evidence that in most-if not all
      neurodegenerative disorders, impaired protein clearance fundamentally contributes
      to functional and structural alterations eventually leading to clinical symptoms.
      Dysfunction of protein clearance leads to intra- and extraneuronal accumulation
      of misfolded proteins and aggregates. The pathological hallmark of Lewy body
      disorders (LBDs) is the abnormal accumulation of misfolded proteins such as alpha
      synuclein (Asyn) and amyloid-beta (Abeta) in a specific subset of neurons, which
      in turn has been related to deficits in protein clearance. In this paper we will
      highlight common intraneuronal (including autophagy and unfolded protein stress
      response) and extraneuronal (including interaction of neurons with astrocytes and
      microglia, phagocytic clearance, autoimmunity, cerebrospinal fluid transport, and
      transport across the blood-brain barrier) protein clearance mechanisms, which may
      be altered across the spectrum of LBDs. A better understanding of the pathways
      underlying protein clearance-in particular of Asyn and Abeta-in LBDs may result
      in the identification of novel biomarkers for disease onset and progression and
      of new therapeutic targets.

PMID- 23133790
TI  - Turris babylonia; re-evaluation of a species complex and description of Turris
      assyria, new species.
AB  - Turris babylonia (Linnaeus, 1758) is the designated type species of Turris, the
      nominate genus of the family Turridae. This species has unusual taxonomic
      significance, since the family Turridae is a large biodiverse group that has been
      highly problematic in its taxonomy. In this article, we address the identity of
      Turris babylonia: molecular data presented here and expanded elsewhere
      demonstrate that two distinctive varieties with divergent shell morphology, both
      conventionally assigned to Turris babylonia, are in fact different species. We
      describe one of the forms as Turris assyria, new species. Thus, specimens
      previously assigned to Turris babylonia now comprise at least two taxa, Turris
      babylonia and Turris assyria; it remains possible that each is a multi-species
      complex. Some of the numerous varieties and morphologically divergent forms in
      each complex may prove not to be conspecific with the two species, each precisely
      defined in this work by a specific barcode sequence.

PMID- 23133791
TI  - Launch of the american journal of nuclear medicine and molecular imaging.

PMID- 23133792
TI  - Intravenous administration of diazepam significantly reduces brown fat activity
      on 18F-FDG PET/CT.
AB  - BACKGROUND: Brown adipose tissue (BAT) activity on (18)F-fluorodeoxyglucose (FDG)
      PET/CT can introduce an undesirable element of complexity when attempting to
      discern physiologic activity from more ominous entities. Recent studies have
      demonstrated several methods to reduce BAT FDG uptake. Benzodiazepines, however,
      have yet to been proven effective against BAT. METHODS: Twenty-five patients with
      increased BAT FDG uptake were selected retrospectively from our PET/CT database
      between November 2004 and January 2011. These patients had been asked to return
      on a different day for repeat scanning with 5mg of intravenous diazepam,
      administered ten minutes prior to FDG. Two patients underwent this procedure on a
      second occasion (for a follow-up scan at a later date), thus resulting in a total
      of twenty-seven scans from twenty five patients. FDG uptake in BAT was recorded
      using the maximum standardized uptake value (SUVmax). RESULTS: The mean basal BAT
      SUVmax was 10.1 +/- 4.6 compared to a mean SUVmax of 2.8 +/- 3.3 post IV diazepam
      (p < 0.0001). Approximately 89% (24 of 27) of scans had no significant residual
      BAT activity. The three remaining scans had a reduction in SUVmax ranging from 23
      64% following diazepam administration. No adverse effects were noted. CONCLUSION:
      We observed a significant reduction in brown fat activity in para-spinal,
      cervical, mediastinal, para-adrenal, and supra- and infra-clavicular regions on
      PET/CT following premedication with intravenous diazepam. We feel that IV
      benzodiazepines should be considered a pharmacologic option for reducing BAT FDG
      uptake, which in turn, will aid in distinguishing physiologic metabolic activity
      from pathology.

PMID- 23133793
TI  - Development of NGR peptide-based agents for tumor imaging.
AB  - Molecular imaging allows direct visualization of targets and characterization of
      cellular pathways, as long as a high signal/background ratio can be achieved,
      which requires a sufficient amount of probes to accumulate in the imaging region.
      The Asn-Gly-Arg (NGR) tripeptide selected by phage display can specifically
      target tumor vasculature. Recognizing the aminopeptidase N (APN or CD13) receptor
      on the membrane of tumor cells, the peptide can be further internalized into
      cytoplasma by the endosomal pathway. Hence NGR can serve as an ideal candidate
      for tumor imaging, once it is conjugated with fluorescent or radiolabeled imaging
      probes. Herein, we highlight some recent developments of NGR peptide based
      imaging of tumors. Although still in the preliminary stage, some NGR probes have
      shown potential as promising agents in future clinical applications.

PMID- 23133794
TI  - (18)F-FDG PET in sarcoma treatment response imaging.
AB  - Sarcomas are a biologically complex group of diseases that exhibit variable
      responses to single or combination therapy. (18)F-FDG PET imaging contributes to
      sarcoma treatment response assessment as an objective semiquantitative biomarker
      of response. In this review, background and experience in (18)F-FDG PET as a
      biomarker that successfully identifies tumor response is assessed.

PMID- 23133795
TI  - How to study optimal timing of PET/CT for monitoring of cancer treatment.
AB  - PURPOSE: The use of PET/CT for monitoring treatment response in cancer patients
      after chemo- or radiotherapy is a very promising approach to optimize cancer
      treatment. However, the timing of the PET/CT-based evaluation of reduction in
      viable tumor tissue is a crucial question. We investigated how to plan and
      analyze studies to optimize this timing. METHODS: General considerations about
      studying the optimal timing are given and four fundamental steps are illustrated
      using data from a published study. RESULTS: The optimal timing should be examined
      by optimizing the schedule with respect to predicting the overall individual time
      course we can observe in the case of dense measurements. The optimal timing needs
      not to and should not be studied by optimizing the association with the prognosis
      of the patient. CONCLUSIONS: The optimal timing should be examined in specific
      'schedule optimizing studies'. These should be clearly distinguished from studies
      evaluating the prognostic value of a reduction in viable tumor tissue.

PMID- 23133796
TI  - (18)F-FDG PET/CT: timing for evaluation of response to therapy remains a clinical
      challenge.
AB  - Utilizing novel imaging modalities for defining response and predicting long-term
      outcome after treatment may have a significant impact on cancer patient
      management. (18)F-FDG PET/CT has great potential for use in early assessment of
      response to cancer therapy. However, the lack of a general consensus on a
      specific set of response criteria makes adoption of PET difficult for the
      oncology community. The optimal time after initiating therapy for assessing
      response to treatment also has yet to be clearly determined.

PMID- 23133797
TI  - Peptoid-based PET imaging of vascular endothelial growth factor receptor (VEGFR)
      expression.
AB  - Non-invasive detection of vascular endothelial growth factor receptor 2 (VEGFR2)
      by positron emission tomography (PET) would allow the evaluation of tumor
      vascular activity in vivo. Recently, a dimeric peptoid, GU40C4, was reported as a
      highly potent antagonist of VEGFR2 activation inhibiting angiogenesis and tumor
      growth in vivo. The purpose of this work was to evaluate the potential of this
      peptoid for PET imaging of VEGFR2 expression. To label GU40C4 and a control
      peptoid with a positron emitter, (64)Cu (t(1/2) = 12.7 h; beta(+): 0.653 MeV,
      17.4%), a cysteine was introduced to the C-terminus of the peptoids and then
      conjugated to a bifunctional chelator (DOTA: 1,4,7,10-tetraazacyclododecane
      1,4,7,10-tetraacetic acid) through the maleimide-thiol coupling chemistry. The in
      vitro binding assay showed a negligible effect of the DOTA conjugation on the
      VEGFR2 binding affinity of GU40C4. Both peptoid conjugates were efficiently
      labeled with (64)Cu in high radiochemical yields (> 90%); the specific activity
      was in the range of 10 - 80 GBq/MUmol. PET imaging evaluation using a prostate
      cancer xenograft (PC3) mouse model showed that (64)Cu-DOTA-GU40C4 had a prominent
      and steady accumulation in the VEGFR2 positive PC3 tumors (2.25 +/- 0.24, 2.15 +/
      0.34, and 1.90 +/- 0.18 %ID/g at 1, 4, and 20 h p.i., respectively; n = 3),
      which is significantly higher than the control peptoid conjugate (0.3 - 0.5
      %ID/g; p < 0.001 at 1, 4, and 20 h p.i.). Interestingly, the mouse salivary
      glands were also clearly visualized by (64)Cu-DOTA-GU40C4 (3.17 +/- 0.25, 3.00 +/
      0.36, and 1.83 +/- 0.21 %ID/g at 1, 4, and 20 h p.i., respectively; n = 3)
      rather than its control peptoid conjugate. VEGFR2 expression in the salivary
      glands was shown by polymerase chain reaction (PCR) assay. Our results
      demonstrate that (64)Cu-DOTA-GU40C4 can be used to image the expression of VEGFR2
      in vivo.

PMID- 23133798
TI  - American Journal of Nuclear Medicine and Molecular Imaging: Editorial Board
      (2011) e-Century Publishing Corporation.

PMID- 23133799
TI  - Synthesis, radiolabelling and in vitro and in vivo evaluation of a novel
      fluorinated ABP688 derivative for the PET imaging of metabotropic glutamate
      receptor subtype 5.
AB  - (E)-3-(Pyridin-2-ylethynyl)cyclohex-2-enone O-(2-(3-(18)F-fluoropropoxy)ethyl)
      oxime ([(18)F]-PSS223) was evaluated in vitro and in vivo to establish its
      potential as a PET tracer for imaging metabotropic glutamate receptor subtype 5
      (mGluR5). [(18)F]-PSS223 was obtained in 20% decay corrected radiochemical yield
      whereas the non-radioactive PSS223 was accomplished in 70% chemical yield in a
      S(N)2 reaction of common intermediate mesylate 8 with potassium fluoride. The in
      vitro binding affinity of [(18)F]-PSS223 was measured directly in a Scatchard
      assay to give K(d) = 3.34 +/- 2.05 nM. [(18)F]-PSS223 was stable in PBS and rat
      plasma but was significantly metabolized by rat liver microsomal enzymes, but to
      a lesser extent by human liver microsomes. Within 60 min, 90% and 20% of [(18)F]
      PSS223 was metabolized by rat and human microsome enzymes, respectively. In vitro
      autoradiography on horizontal rat brain slices showed heterogeneous distribution
      of [(18)F]-PSS223 with the highest accumulation in brain regions where mGluR5 is
      highly expressed (hippocampus, striatum and cortex). Autoradiography in vitro
      under blockade conditions with ABP688 confirmed the high specificity of [(18)F]
      PSS223 for mGluR5. Under the same blocking conditions but using the mGluR1
      antagonist, JNJ16259685, no blockade was observed demonstrating the selectivity
      of [(18)F]-PSS223 for mGluR5 over mGluR1. Despite favourable in vitro properties
      of [(18)F]-PSS223, a clear-cut visualization of mGluR5-rich brain regions in vivo
      in rats was not possible mainly due to a fast clearance from the brain and low
      metabolic stability of [(18)F]-PSS223.

PMID- 23133800
TI  - PET imaging of metabotropic glutamate receptor subtype 5 (mGluR5).
AB  - Metabotropic glutamate receptors (mGluRs) belong to a family of G-protein coupled
      receptors involved in the modulation of fast excitatory transmission. In
      particular, the subtype-5 receptor (mGluR5) was found to be an attractive target
      for the treatment and diagnosis of variety of psychiatric and neurological
      disease including anxiety, depression, epilepsy, drug addiction, and Parkinson's
      disease. Positron emission tomography (PET) is a highly sensitive imaging
      technique that holds great potential for the diagnosis of a brain disorder. In
      the study published in the American Journal of Nuclear Medicine and Molecular
      Imaging, a (18)F labelled PET probe was developed targeting mGluR5. This paper
      represents the efforts and challenges on the design and development of novel PET
      tracers for mGluR5 imaging.

PMID- 23133801
TI  - The clinical use of PET with (11)C-acetate.
AB  - The aim of this review is to evaluate clinical applications of (11)C-acetate
      positron emission tomography (PET). Acetate is quickly metabolized into acetyl
      CoA in human cells. In this form it can either enter into the tricarboxylic acid
      cycle, thus producing energy, as happens in the myocardium, or participate in
      cell membrane lipid synthesis, as happens in tumor cells. (11)C-acetate PET was
      originally employed in cardiology, to study myocardial oxygen metabolism. More
      recently it has also been used to evaluate myocardial perfusion, as well as in
      oncology. The first studies of (11)C-acetate focused on its use in prostate
      cancer. Subsequently, (11)C-acetate was studied in other urological malignancies,
      as well as renal cell carcinoma and bladder cancer. Well differentiated
      hepatocellular carcinoma represents an (18)F-fluoro-deoxyglucose ((18)F-FDG) PET
      pitfall, so many authors have proposed to use (11)C-acetate in addition to (18)F
      FDG in studying this tumor. (11)C-acetate PET has also been used in other
      malignancies, such as brain tumors and lung carcinoma. Some authors reported a
      few cases in which (11)C-acetate PET incidentally found multiple myeloma or rare
      tumors, such as thymoma, multicentric angiomyolipoma of the kidney and
      cerebellopontine angle schwannoma. Lastly, (11)C-acetate PET was also employed in
      a differential diagnosis case between glioma and encephalitis. The numerous
      studies on (11)C-acetate have demonstrated that it can be used in cardiology and
      oncology with no contraindications apart from pregnancy and the necessity of a
      rapid scan. Despite its limited availability, this tracer can surely be
      considered to be a promising one, because of its versatility and capacity to even
      detect non (18)F-FDG-avid neoplasm, such as differentiated lung cancer or
      hepatocellular carcinoma.

PMID- 23133802
TI  - Positron emission tomography (PET) imaging with (18)F-based radiotracers.
AB  - Positron Emission Tomography (PET) is a nuclear medicine imaging technique that
      is widely used in early detection and treatment follow up of many diseases,
      including cancer. This modality requires positron-emitting isotope labeled
      biomolecules, which are synthesized prior to perform imaging studies. Fluorine-18
      is one of the several isotopes of fluorine that is routinely used in
      radiolabeling of biomolecules for PET; because of its positron emitting property
      and favorable half-life of 109.8 min. The biologically active molecule most
      commonly used for PET is 2-deoxy-2-(18)F-fluoro-beta-D-glucose ((18)F-FDG), an
      analogue of glucose, for early detection of tumors. The concentrations of tracer
      accumulation (PET image) demonstrate the metabolic activity of tissues in terms
      of regional glucose metabolism and accumulation. Other tracers are also used in
      PET to image the tissue concentration. In this review, information on
      fluorination and radiofluorination reactions, radiofluorinating agents, and
      radiolabeling of various compounds and their application in PET imaging is
      presented.

PMID- 23133803
TI  - Preoperative 123I-iomazenil SPECT imaging predicts cerebral hyperperfusion
      following endarterectomy for unilateral cervical internal carotid artery
      stenosis.
AB  - PURPOSE: Cerebral hyperperfusion following carotid endarterectomy (CEA) occurs in
      patients with preoperative impairments in cerebral hemodynamics. The aim of the
      present study was to determine whether late images/early images on preoperative
      brain (123)I-iomazenil (IMZ) single-photon emission computed tomography (SPECT),
      which correlate with oxygen extraction fraction images on positron emission
      tomography, could identify patients at risk for cerebral hyperperfusion following
      endarterectomy for unilateral cervical internal carotid artery (ICA) stenosis.
      METHODS: In 80 patients, preoperative brain SPECT scans were initiated
      immediately after (early images) and 180 min after (late images) administration
      of (123)I-IMZ. A region of interest (ROI) was automatically placed in the middle
      cerebral artery territory in both the cerebral hemispheres using a three
      dimensional stereotaxic ROI template. Transcranial regional cerebral oxygen
      saturation (rSO(2)) was monitored using near-infrared spectroscope throughout
      carotid endarterectomy, and a patient was defined as having cerebral
      hyperperfusion when a ratio of rSO(2) at the end of the surgery to rSO(2) before
      ICA clamping was >= 1.1. RESULTS: Cerebral hyperperfusion was observed on
      intraoperative rSO(2) monitoring in eight patients (10%). Preoperative increase
      in affected side-to-contralateral side asymmetry on late/early (123)I-IMZ value
      was the only significant independent predictor of cerebral hyperperfusion (95%
      confidence interval [CI], 1.606 to 8.710; P = 0.0010). The preoperative
      late/early (123)I-IMZ asymmetry corresponded to an 88% sensitivity and 89%
      specificity, with 47% positive- and 98% negative-predictive values for the
      development of cerebral hyperperfusion. CONCLUSIONS: Preoperative late/early
      (123)I-IMZ images can identify patients at risk for cerebral hyperperfusion
      following endarterectomy for unilateral cervical ICA stenosis.

PMID- 23133804
TI  - Comparative functional evaluation of immunocompetent mouse breast cancer models
      established from PyMT-tumors using small animal PET with [(18)F]FDG and
      [(18)F]FLT.
AB  - Positron emission tomography (PET) allows detection of functional changes in
      malignant tissue. Establishment of an immortalized immunocompetent breast cancer
      mouse model would provide a useful platform for the analysis of novel cancer
      treatment strategies. This study describes a comparative functional evaluation of
      murine breast cancer models established from polyoma virus middle T antigen
      (PyMT)-derived tumors using small animal PET imaging with [(18)F]FDG and
      [(18)F]FLT. Primary PyMT tumor-derived cells and a cell line derived from these
      tumors (MTHJ) were injected subcutaneously into immunocompetent FVB mice to
      generate breast cancer xenografts. Tumor growth rates were comparable in both
      models and tumors were analyzed after 4-5 weeks post-injection. [(18)F]FDG uptake
      in vitro followed a comparable trend in both models but reached higher uptake
      levels in primary PyMT cells vs. MTHJ cells after 120 min. At all time points,
      [(18)F]FLT uptake was significantly higher in MTHJ compared to primary PyMT
      cells. Dynamic small animal PET imaging with [(18)F]FDG revealed standardized
      uptake values (SUVs) of 2.5+/-0.1 (n=8) in tumors from primary cells and 2.8+/
      0.4 (n=6) in MTHJ tumors after 60 min p.i.. The corresponding tumor-muscle-ratios
      were 9.3+/-1.5 and 10.4+/-0.9, respectively. Uptake of [(18)F]FLT resulted in
      slightly higher SUV(60min) in MTHJ tumors (1.1+/-0.1, n=6) compared to tumors
      from primary cells (SUV(60min)=0.9+/-0.05, n=8, p=0.07). The tumor-muscle-ratio
      was comparable in both tumors (2.1+/-0.2 and 1.8+/-0.1, respectively). The PET
      imaging data demonstrates that the functional profile of immunocompetent murine
      breast tumor model MTHJ remains the same as in primary-derived PyMT tumors in
      vivo. Metabolic and proliferative rates as assessed with [(18)F]FDG and
      [(18)F]FLT are comparable in both tumor models. The observed high SUV(60min) of
      2.8+/-0.4 with [(18)F]FDG in MTHJ tumors allows one to monitor efficacy of
      therapeutic interventions connected with changes in metabolic response of the
      tumor by means of small animal PET.

PMID- 23133805
TI  - Non-invasive longitudinal imaging of tumor progression using an (111)indium
      labeled CXCR4 peptide antagonist.
AB  - The chemokine receptor 4 (CXCR4) is a biomarker that is over-expressed in ductal
      carcinoma in situ (DCIS). Hence, CXCR4-targeted (molecular) imaging approaches
      may have diagnostic value in such a challenging, premalignant lesion. The indium
      labeled CXCR4 peptide-antagonist, (111)In-DTPA-Ac-TZ14011, was used to visualize
      CXCR4-expression in a mammary intraepithelial neoplastic outgrowth (MIN-O) mouse
      tumor model resembling human DCIS. MIN-O lesion development was longitudinally
      monitored using SPET/CT and tracer uptake was compared to uptake in control
      lesions. Expression of CXCR4 was validated using immunohistochemistry and flow
      cytometric analysis. The uptake of (111)In-DTPA-Ac-TZ14011 was related to tumor
      angiogenesis using (111)In-cDTPA-[RGDfK]. Twenty-four hours after tracer
      injection, MIN-O lesions could be discriminated from low CXCR4-expressing control
      tumors, while the degree of angiogenesis based on the alpha(v)beta(3) integrin
      expression in both tumor types was similar. The uptake of (111)In-DTPA-Ac-TZ14011
      in early MIN-O lesions was significantly lower than in larger intermediate and
      late-stage lesions, two-and-a-half-times (p=0.03) and seven-times (p=0.002),
      respectively. Intermediate and late stage lesions show a higher degree of
      membranous CXCR4-staining at immunohistochemistry and flow cytometric analysis.
      From this study we can conclude that (111)In-DTPA-Ac-TZ14011 can be used to
      visualize the CXCR4-expression in MIN-O lesions longitudinally.

PMID- 23133806
TI  - Molecular imaging of therapy response with (18)F-FLT and (18)F-FDG following
      cyclophosphamide and mTOR inhibition.
AB  - PURPOSE: Evaluation and comparison of 3'-[(18)F]-fluoro-3'-deoxy-L-thymidine
      (FLT) and 2-[(18)F]-fluoro-2-deoxyglucose (FDG)-PET to monitor early response
      following both cyclophosphamide and temsirolimus treatment in a mouse model of
      Burkitt lymphoma. METHODS: Daudi xenograft mice were treated with either
      cyclophosphamide or temsirolimus and imaged with FLT-PET and FDG-PET on
      appropriate days post therapy inititiation. Immunohistochemical (IHC) studies
      (H&E, TUNEL, CD20, PCNA and ki-67) and DNA flow cytometry studies were performed.
      RESULTS: FDG tumor uptake decreased immediately after cyclophosphamide treatment
      while FLT-PET showed only a late and less pronounced decrease. A fast induction
      of apoptosis was observed together with an early accumulation of cells in the S
      phase of the cell cycle, suggesting DNA repair. Temsirolimus treatment reduced
      both FDG and FLT tumor uptake immediately after therapy and resulted in a fast
      induction of apoptosis and G(0)-G(1) phase accumulation. CONCLUSION: FLT response
      was less distinct than FDG response and may be controlled by DNA repair early
      after cyclophosphamide. Nevertheless, FLT-PET was able to reflect decreased
      proliferation following temsirolimus.

PMID- 23133807
TI  - Synthesis and characterization of intrinsically radiolabeled quantum dots for
      bimodal detection.
AB  - A novel approach was developed to synthesize radioactive quantum dots (r-QDs)
      thereby enabling both optical and radionuclide signals to be detected from the
      same intrinsic bimodal probe. This proof-of-concept is exemplified by the
      incorporation of the radionuclide (109)Cadmium into the core/shell of the
      nanoparticle. Green and near infrared (NIR) emission intrinsic r-QDs were
      synthesized and characterized. Zwitterionic and Poly-polyethlene glycol
      (PEGylated) ligands were synthesized and used to coat r-QDs. Zwitterionic NIR r
      QDs (quantum yield = 11%) and PEGylated NIR r-QDs (quantum yield = 14%) with an
      average size of 13.8 nm and 16.8 nm were obtained respectively. The
      biodistribution of NIR zwitterionic and PEGylated r-QDs in nude mice was
      investigated and zwitterionic r-QDs showed longer blood circulation (t(1/2) =
      21.4+/-1.1 hrs) than their PEGylated counterparts (t(1/2) = 6.4+/-0.5 min). Both
      zwitterionic and PEGylated r-QDs exhibited progressive accumulation in the liver
      and spleen, but the magnitude of the accumulation (%ID/g) was about 3-6 fold
      higher with the PEGylated r-QDs at all the time points. The results demonstrated
      the feasibility of r-QDs synthesis in quantitative yield and retention of
      fluorescence following incorporation of radioactivity into the core/shell of the
      nanoparticle. The gamma signal from the same fluorescent elemental material
      enabled quantitative and robust pharmacokinetic measurements and how these
      changed depended on the type of coating ligands used. This strategy for
      intrinsically radio-labeling the QDs is currently being implemented in our
      laboratory for the incorporation of other radiometals.

PMID- 23133808
TI  - In a "nutshell": intrinsically radio-labeled quantum dots.
AB  - Quantum dots (QDs) have many intriguing properties suitable for biomedical
      imaging applications. The poor tissue penetration of optical imaging in general,
      including those using QDs, has motivated the development of various QD-based dual
      modality imaging agents. In this issue of AJNMMI (http://www.ajnmmi.us), Sun et
      al. reported the synthesis and in vitro/in vivo characterization of intrinsically
      radio-labeled QDs (r-QDs), where (109)Cd was incorporated into the core/shell of
      QDs of various compositions. These r-QDs emit in the near-infrared range, have
      long circulation half-life, are quite stable with low cytotoxicity, exhibit small
      size and low accumulation in the reticuloendothelial system, and can allow for
      accurate measurement of their biodistribution in mice. With these desirable
      features demonstrated in this study, future development and optimization will
      further enhance the biomedical potential of intrinsically radio-labeled QDs.

PMID- 23133809
TI  - In vitro autoradiography of carcinoembryonic antigen in tissue from patients with
      colorectal cancer using multifunctional antibody TF2 and (67/68Ga)-labeled
      haptens by pretargeting.
AB  - The carcinoembryonic antigen (CEA) was visualized in vitro in tissue from
      patients with colorectal cancer with trivalent bispecific antibody TF2 and two
      hapten molecules, [(67/68)Ga]Ga-IMP461 and [(67/68)Ga]Ga-IMP485 by means of
      pretargeting. Colorectal cancer tissue samples obtained from surgery at Uppsala
      University Hospital, were frozen fresh and cryosectioned. The two hapten
      molecules comprising 1,4,7-triazacyclononanetriacetic acid chelate moiety (NOTA)
      were labeled with (67)Ga or (68)Ga. The autoradiography was conducted by
      incubating the tissue samples with the bispecific antibody TF2, followed by
      washing and incubation with one of the radiolabeled hapten molecules. After
      washing, drying and exposure to phosphor imager plates, the autoradiograms were
      analyzed and compared to standard histochemistry (hematoxylin-eosin). Pronounced
      binding was found in the tissue from colorectal cancer using the bispecific
      antibody TF2 and either of the haptens [(67/68)Ga]Ga-IMP461 and [(67/68)Ga]Ga
      IMP485. Distinct binding was also detected in the epithelium of most samples of
      neighboring tissue, taken at a minimum of 10 cm from the site of the tumor. It is
      concluded that pretargeting CEA with the bispecific antibody TF2 followed by the
      addition of (67/68)Ga-labeled hapten is extremely sensitive for visualizing this
      marker for colorectal cancer. This methodology is therefore a very specific
      complement to other histochemical techniques in the diagnosis of biopsies or in
      samples taken from surgery. Use of the pretargeting technique in vivo may also be
      an advance in diagnosing patients with colorectal cancer, either using (67)Ga and
      SPECT or (68)Ga and PET.

PMID- 23133810
TI  - Multispectral visualization of surgical safety-margins using fluorescent marker
      seeds.
AB  - Optical guidance provided by luminescent marker seeds may be suitable for
      intraoperative determination of appropriate resection margins. In phantom studies
      we compared the tissue penetration of several organic dyes and inorganic
      particles (quantum dots; QDs) after incorporation in experimental marker seeds.
      The tissue penetration of (near infra-) red organic dyes was much better than the
      penetration of dyes and QDs with an emission in the visible range. By combining 3
      dyes in a single marker seed we were able to distinguish four depth ranges. The
      difference in tissue penetration between the dyes and QDS enabled depth
      estimation via a 'traffic light' approach.

PMID- 23133811
TI  - Cerenkov imaging - a new modality for molecular imaging.
AB  - Cerenkov luminescence imaging (CLI) is an emerging hybrid modality that utilizes
      the light emission from many commonly used medical isotopes. Cerenkov radiation
      (CR) is produced when charged particles travel through a dielectric medium faster
      than the speed of light in that medium. First described in detail nearly 100
      years ago, CR has only recently applied for biomedical imaging purposes. The
      modality is of considerable interest as it enables the use of widespread
      luminescence imaging equipment to visualize clinical diagnostic (all PET
      radioisotopes) and many therapeutic radionuclides. The amount of light detected
      in CLI applications is significantly lower than other that in other optical
      imaging techniques such as bioluminescence and fluorescence. However, significant
      advantages include the use of approved radiotracers and lack of an incident light
      source, resulting in high signal to background ratios. As well, multiple subjects
      may be imaged concurrently (up to 5 in common bioluminescent equipment),
      conferring both cost and time benefits. This review summarizes the field of
      Cerenkov luminescence imaging to date. Applications of CLI discussed include
      intraoperative radionuclide-guided surgery, monitoring of therapeutic efficacy,
      tomographic optical imaging capabilities, and the ability to perform multiplexed
      imaging using fluorophores excited by the Cerenkov radiation. While technical
      challenges still exist, Cerenkov imaging has materialized as an important
      molecular imaging modality.

PMID- 23133813
TI  - Pictorial review of SPECT/CT imaging applications in clinical nuclear medicine.
AB  - Integrated SPECT/CT scanners are gaining popularity as hybrid molecular imaging
      devices which can acquire SPECT and CT in a single exam. CT can be a low dose non
      contrast enhanced scan for attenuation correction and anatomical localization, or
      a contrast enhanced diagnostic quality scan for additional anatomical
      characterization. We present a pictorial review highlighting the usefulness of
      this emerging technology. We present SPECT/CT images of 13 patients where
      additional information was provided by the co-registered low dose non-contrast
      enhanced CT scan. They belong to 12 male and 1 female patients with age ranging
      from 28 to 76 yrs, who were referred to the Nuclear Medicine Department for
      various indications. We describe these cases under in the following categories:
      bone scintigraphy (2), leukocyte scintigraphy (2), nuclear oncology (5), nuclear
      cardiology (1), and general nuclear medicine (3). Additional information provided
      by the co-registered low dose CT improves the diagnostic confidence in image
      interpretation of SPECT imaging.

PMID- 23133814
TI  - In vivo and ex vivo applications of gold nanoparticles for biomedical SERS
      imagingi.
AB  - Surface enhanced Raman scattering (SERS) is a signal-increasing phenomenon that
      occurs whenever Raman scattering on a metal surface is enhanced many orders of
      magnitude. Recently SERS has received considerable attention due to its
      ultrasensitive multiplex imaging capability with strong photostability. It
      provides rich molecular information on any Raman molecule adsorbed to rough metal
      surfaces. The signal enhancement is so remarkable that identification of a single
      molecule is possible. SERS has become a genuine molecular imaging technique. Gold
      nanoparticles, encoded with Raman reporters, provide a SERS signal and have been
      used as imaging probes, often referred to as SERS nanoparticles. They have been
      used for molecular imaging in vivo, ex vivo and in vitro. Detection of picomolar
      concentrations of target molecules has been achieved by functionalizing the
      nanoparticles with target recognition ligands. This review focuses on recent
      achievements in utilizing SERS nanoparticles for in vivo molecular imaging. In
      the near future, SERS technology may allow detection of disease markers at the
      single cell level.

PMID- 23133815
TI  - Efficacy of (99m)Tc-EDDA/HYNIC-TOC SPECT/CT scintigraphy in Graves'
      ophthalmopathy.
AB  - The aim of this study was to investigate the predictive role of the orbital
      somatostatin receptor scintigraphy with (99m)Tc-EDDA/HYNIC-TOC ((99m)Tc-TOC) to
      detect clinical stage of Graves' ophthalmopathy and the response to
      corticosteroid therapy. The subjects of the experiment were 46 patients with
      Graves' ophthalmopathy (GO) and four volunteers without eye disease or GO as the
      normal group (NG). Single photon emission computed tomography (SPECT), computed
      tomography (CT) and the left and right lateral position planar imaging of the
      heads of the all subjects were obtained 4 h after the intravenous injection of
      555 MBq of (99m)Tc-TOC. The (99m)Tc-TOC SPECT/CT was repeated 3 months later. 35
      (35/46) patients were received corticosteroid therapy (prednisolone, 10 mg po tid
      ) for 3 months, however, the other 11 patients as control groups did not receive
      any treatment. The treatment effect was evaluated both by the orbital (99m)Tc-TOC
      uptake and NOSPECS. A significant decrease in the O/OC ratio was observed in 22
      GO patients between pre- and post-treatment (1.64 +/- 0.13 vs. 1.21 +/- 0.09, P <
      0.05). There were neither significant difference of the O/OC ratio in 13 GO
      patients between pre- and post-treatment periods, nor significant difference in
      the 9 (9/11) patients before and after three months. Orbital (99m)Tc-TOC
      scintigraphy is a feasible technique to estimate the Graves' ophthalmopathy
      activity and predict the response to subsequent corticosteroid therapy in GO
      patients. The technique could be a useful tool for physicians not familiar with
      CAS determination.

PMID- 23133812
TI  - Current imaging strategies in rheumatoid arthritis.
AB  - As remission has now become a realistic therapeutic goal in the clinical
      management of RA due to the introduction and widespread adoption of biologic
      agents, there is a greater need for earlier diagnoses and objective methods for
      evaluating disease activity and response to treatment. In this capacity, advanced
      imaging strategies are assuming an expansive clinical role, particularly as they
      take advantage of newer imaging technologies and the shift toward imaging at the
      molecular level. Molecular imaging utilizes target-specific probes to non
      invasively visualize molecular, cellular, and physiological perturbations in
      response to the underlying pathology. Probes for nuclear and MR imaging have been
      and are being developed that react with discrete aspects of inflammatory and
      destructive pathways specific to RA. These probes in addition to new MR sequences
      and contrast agents have the potential to provide an earlier and more reliable
      assessment of clinical outcome, disease activity, severity, and location, and
      therapeutic response. Furthermore, these imaging strategies may enable a more
      fundamental understanding of critical pathophysiological processes and the advent
      of new molecular therapies. This review will discuss these advances in both
      nuclear medicine and MRI strategies for imaging RA with a particular emphasis on
      molecular imaging.

PMID- 23133816
TI  - [(125)I]FIAU imaging in a preclinical model of lung infection: quantification of
      bacterial load.
AB  - 2'-Fluoro-2'-deoxy-1beta-D-arabinofuranosyl-5-[(125)I]iodouracil ([(125)I]FIAU),
      a substrate for the thymidine kinase (TK) present in most bacteria, has been used
      as an imaging agent for single photon emission computed tomography (SPECT) in an
      experimental model of lung infection. Using SPECT-CT we show that [(125)I]FIAU is
      specific for bacterial infection rather than sterile inflammation. We report
      [(125)I]FIAU lung uptake values of 1.26 +/- 0.20 percent injected dose per gram
      (%ID/g) in normal controls, 1.69 +/- 0.32 %ID/g in lung inflammation and up to
      7.14 +/- 1.09 %ID/g in lung infection in ex vivo biodistribution studies at 24 h
      after intranasal administration of bacteria. Images of [(125)I]FIAU signal within
      lung can be used to estimate the number of bacteria present, with a limit of
      detection of 10(9) colony forming units per mL on the X-SPECT scanner.
      [(125)I]FIAU-Based bacterial imaging may be useful in preclinical models to
      facilitate the development of new antibiotics, particularly in cases where a
      corresponding human trial is planned.

PMID- 23133817
TI  - FIAU: From reporter gene imaging to imaging of bacterial proliferation.
AB  - The radioiodinated thymidine analogue, FIAU, is a tracer that has been developed
      for reporter gene, for cells that were transfected with herpes simplex virus
      thymidine kinase, HSV-TK. FIAU is also a specific substrate of bacterial TK due
      to the homology between viral and bacterial TK. In this issue of AJNMMI
      (http://www.ajnmmi.us), Pullamb-hatla et al. reported that the accumulation of
      (125)I-FIAU in pulmonary infectious foci correlated with the bacterial burden in
      the lungs. (125)I-FIAU could be used to monitor the efficacy of anti-microbial
      therapy in mice. Potentially (124)I-FIAU PET could be used to discriminate
      microbial from sterile inflammation in patients with prosthetic implants.

PMID- 23133818
TI  - The role of PET/CT in decreasing inter-observer variability in treatment planning
      and evaluation of response for cervical cancer.
AB  - We have previously introduced anatomic biologic contouring (ABC) with PET/CT,
      using a distinct "halo" to unify contouring methods in treatment planning for
      lung and head and neck cancers. The objective of this study is to assess the
      utility of PET/CT in planning and treatment response for cervical cancer. Forty
      two patients with stages II-IIIB cervix cancer were planned for irradiation using
      PET/CT. A CT-based Gross Tumor Volume (GTV-CT) was delineated by two independent
      observers while the PET remained obscured. The Planning Target Volume (PTV) was
      obtained by adding a 1.5 cm margin around the GTV. The same volumes were
      recontoured using PET/CT data and termed GTV-ABC and PTV-ABC, respectively. The
      values of GTV-CT and GTV-ABC and the absolute differences between the two
      observers were analyzed. Additionally, 23 of these patients had PET/CT performed
      3 months after treatment. The anatomic biologic value (ABV) was calculated using
      the product of maximum diameter and mean SUV of the cervical tumor. The pre- and
      post-treatment ABVs were compared. A "halo" was observed around areas of maximal
      SUV uptake. The mean halo SUV was 1.91 +/- 0.56 (SD). The mean halo thickness was
      2.12 +/- 0.5 (SD) mm. Inter-observer GTV variability decreased from a mean volume
      difference of 55.36 cm(3) in CT-based planning to 12.29 cm(3) in PET/CT-based
      planning with a respective decrease in standard deviation (SD) from 55.78 to
      10.24 (p <0.001). Comparison of mean pre-treatment and post-treatment ABV's
      revealed a decrease of ABV from 48.2 to 7.8 (p<0.001). PET/CT is a valuable tool
      in radiation therapy planning and evaluation of treatment response for cervical
      cancer. A clearly visualized "halo" was successfully implemented in GTV
      contouring in cervical cancer, resulting in decreased inter-observer variability
      in planning. PET/CT has the ability to quantify treatment response using anatomic
      biologic value.

PMID- 23133820
TI  - Impact of expectation-maximization reconstruction iterations on the diagnosis of
      temporal lobe epilepsy with PET.
AB  - There is a well known tradeoff between image noise and image sharpness that is
      dependent on the number of iterations performed in ordered subset expectation
      maximization (OSEM) reconstruction of PET data. We aim to evaluate the impact of
      this tradeoff on the sensitivity and specificity of (18)F-FDG PET for the
      diagnosis of temporal lobe epilepsy. A retrospective blinded reader study was
      performed on two OSEM reconstructions, using either 2 or 5 iterations, of 32
      (18)F-FDG PET studies acquired at our institution for the diagnosis of temporal
      lobe epilepsy. The sensitivity and specificity of each reconstruction for
      identifying patients who were ultimately determined to be surgical candidates was
      assessed using an ROC analysis. The sensitivity of each reconstruction for
      identifying patients who showed clinical improvement following surgery was also
      assessed. Our results showed no significant difference between the two
      reconstructions studied for either the sensitivity and specificity of (18)F-FDG
      PET for predicting surgical candidacy, or its sensitivity for predicting positive
      surgical outcomes. This implies that the number of iterations performed during
      OSEM reconstruction will have little impact on a reader based interpretation of
      (18)F-FDG PET scans acquired for the diagnosis of temporal lobe epilepsy, and can
      be determined by physician and institutional preference.

PMID- 23133821
TI  - Interim analyses in diagnostic versus treatment studies: differences and
      similarities.
AB  - The purpose of this paper was to contrast interim analyses in (randomized
      controlled) treatment studies with interim analyses in paired diagnostic studies
      of accuracy with respect to planning and conduct. The term 'treatment study'
      refers to a (randomized) clinical trial that aims to demonstrate the superiority
      or noninferiority of one treatment compared with another, and the term
      'diagnostic study' to a clinical study that compares two diagnostic procedures,
      using a third diagnostic procedure as the gold standard. Though interim analyses
      in treatment studies and paired diagnostic studies show similarities in a priori
      planning of timing, decision rules, and the consequences of the analyses, they
      differ with respect to (1) the need for sample size adjustments, (2) the
      possibility of early decisions without early stopping, and (3) the impact of
      keeping results secret. These differences are due, respectively, to certain
      characteristics of paired diagnostic studies: the dependence of the sample size
      on the agreement rate between the modalities, multiple aims of diagnostic
      accuracy studies, and the advantages of early unblinding of results at the
      individual level. We exemplified our points by using a recent investigation at
      our institution on the detection of bone metastases from prostate cancer in
      patients with histologically confirmed prostate cancer in which (99m)Tc-MDP whole
      body bone scintigraphy was compared to positron emission tomography/computed
      tomography with (18)F-fluorocholine as tracer, using magnetic resonance imaging
      as a reference.

PMID- 23133819
TI  - Altered sympathetic nervous system signaling in the diabetic heart: emerging
      targets for molecular imaging.
AB  - Diabetes is commonly associated with increased risk of cardiovascular morbidity
      and mortality. Perturbations in sympathetic nervous system (SNS) signaling have
      been linked to the progression of diabetic heart disease. Glucose, insulin, and
      free fatty acids contribute to elevated sympathetic nervous activity and
      norepinephrine release. Reduced left ventricular compliance and impaired cardiac
      function lead to further SNS activation. Chronic elevation of cardiac
      norepinephrine culminates in altered expression of pre- and post-synaptic
      sympathetic signaling elements, changes in calcium regulatory proteins, and
      abnormal contraction-excitation coupling. Clinically, these factors manifest as
      altered resting heart rate, depressed heart rate variability, and impaired
      cardiac autonomic reflex, which may contribute to elevated cardiovascular risk.
      Development of molecular imaging probes enable a comprehensive evaluation of
      cardiac SNS signaling at the neuron, postsynaptic receptor, and intracellular
      second messenger sites of signal transduction, providing mechanistic insights
      into cardiac pathology. This review will examine the evidence for abnormal SNS
      signaling in the diabetic heart and establish the physiological consequences of
      these changes, drawing from basic biological research in isolated heart and
      rodent models of diabetes, as well as from clinical reports. Particular attention
      will be paid to the use of molecular imaging approaches to non-invasively
      characterize and evaluate sympathetic signal transduction in diabetes, including
      pre-synaptic norepinephrine reuptake assessment using (11)C-meta-hydroxyephedrine
      ((11)C-HED) with PET or (123)I-metaiodobenzylguanidine ((123)I-MIBG) with SPECT,
      and postsynaptic beta-adrenoceptor density measurements using CGP12177
      derivatives. Finally, the review will attempt to define the future role of these
      non-invasive nuclear imaging techniques in diabetes research and clinical care.

PMID- 23133822
TI  - Bioluminescence imaging of therapy response does not correlate with FDG-PET
      response in a mouse model of Burkitt lymphoma.
AB  - Since the development and evaluation of novel anti-cancer therapies require
      molecular insight in the disease state, both FDG-PET and BLI imaging were
      evaluated in a Burkitt B-cell lymphoma xenograft model treated with
      cyclophosphamide or temsirolimus. Daudi xenograft mice were treated with either
      cyclophosphamide or temsirolimus and imaged with BLI and FDG-PET on d0 (before
      treatment), d2, d4, d7, d9 and d14 following the start of therapy. Besides tumor
      volume changes, therapy response was assessed with immunohistochemical analysis
      (apoptosis). BLI revealed a flare following both therapeutics that was
      significantly higher when compared to control tumors. FDG-PET decreased
      immediatelly, long before the tumor reduced in size. Late after therapy, BLI
      signal intensities decreased significantly compared to baseline subsequent to
      tumor size reduction while apoptosis was immediately induced following both
      treatment regimen. Unlike FDG, BLI was not able to reflect reduced levels of
      viable cells and was not able to predict tumor size response and apoptosis
      response.

PMID- 23133823
TI  - False-positive uptake on radioiodine whole-body scintigraphy: physiologic and
      pathologic variants unrelated to thyroid cancer.
AB  - Radioiodine whole-body scintigraphy (WBS), which takes advantage of the high
      avidity of radioiodine in the functioning thyroid tissues, has been used for
      detection of differentiated thyroid cancer. Radioiodine is a sensitive marker for
      detection of thyroid cancer; however, radioiodine uptake is not specific for
      thyroid tissue. It can also be seen in healthy tissue, including thymus, breast,
      liver, and gastrointestinal tract, or in benign diseases, such as cysts and
      inflammation, or in a variety of benign and malignant non-thyroidal tumors, which
      could be mistaken for thyroid cancer. In order to accurately interpret
      radioiodine scintigraphy results, one must be familiar with the normal
      physiologic distribution of the tracer and frequently encountered physiologic and
      pathologic variants of radioiodine uptake. This article will provide a systematic
      overview of potential false-positive uptake of radioiodine in the whole body and
      illustrate how such unexpected findings can be appropriately evaluated.

PMID- 23133826
TI  - Receptor modified gold and silver nanoparticles: effect on interactions with
      oxoanions.
AB  - Herein we present a supramolecular non-covalent approach for the modification of
      gold nanoparticles (GNPs) and silver nanoparticles (SNPs) with porphyrin
      derivatives. The immobilization of porphyrin derivatives was carried out by two
      different procedures of ionic interaction. The first one was direct
      immobilization of the conjugate on nanoparticles and the second one was
      immobilization of the conjugate on 3-mercaptopropanoic acid (MPA) premodified
      gold nanoparticles. Such modified nanoparticles were used for interactions with
      selected oxoanions. The interactions were studied by UV-Vis absorption
      spectroscopy and electronic circular dichroism. The results showed a dependence
      of interaction with oxoanions on the immobilization procedures of porphyrin
      derivatives on the nanoparticle surface.

PMID- 23133825
TI  - Anti-idiotypic antibodies as cancer vaccines: achievements and future
      improvements.
AB  - Since the discovery of tumor-associated antigens (TAAs), researchers have tried
      to develop immune-based anti-cancer therapies. Thanks to their specificity,
      monoclonal antibodies (mAbs) offer the major advantage to induce fewer side
      effects than those caused by non-specific conventional treatments (e.g.,
      chemotherapy, radiotherapy). Passive immunotherapy by means of mAbs or cytokines
      has proved efficacy in oncology and validated the use of immune-based agents as
      part of anti-cancer treatment options. The next step was to try to induce an
      active immune protection aiming to boost own's host immune defense against TAAs.
      Cancer vaccines are thus developed to specifically induce active immune
      protection targeting only tumor cells while preserving normal tissues from a non
      specific toxicity. But, as most of TAAs are self antigens, an immune tolerance
      against them exists representing a barrier to effective vaccination against these
      oncoproteins. One promising approach to break this immune tolerance consists in
      the use of anti-idiotypic (anti-Id) mAbs, so called Ab2, as antigen surrogates.
      This vaccination strategy allows also immunization against non-proteic antigens
      (such as carbohydrates). In some clinical studies, anti-Id cancer vaccines indeed
      induced efficient humoral and/or cellular immune responses associated with
      clinical benefit. This review article will focus on recent achievements of anti
      Id mAbs use as cancer vaccines in solid tumors.

PMID- 23133824
TI  - Current neuroimaging techniques in Alzheimer's disease and applications in animal
      models.
AB  - With Alzheimer's disease (AD) quickly becoming the most costly disease to
      society, and with no disease-modifying treatment currently, prevention and early
      detection have become key points in AD research. Important features within this
      research focus on understanding disease pathology, as well as finding biomarkers
      that can act as early indicators and trackers of disease progression or potential
      treatment. With the advances in neuroimaging technology and the development of
      new imaging techniques, the search for cheap, noninvasive, sensitive biomarkers
      becomes more accessible. Modern neuroimaging techniques are able to cover most
      aspects of disease pathology, including visualization of senile plaques and
      neurofibrillary tangles, cortical atrophy, neuronal loss, vascular damage, and
      changes in brain biochemistry. These methods can provide complementary
      information, resulting in an overall picture of AD. Additionally, applying
      neuroimaging to animal models of AD could bring about greater understanding in
      disease etiology and experimental treatments whilst remaining in vivo. In this
      review, we present the current neuroimaging techniques used in AD research in
      both their human and animal applications, and discuss how this fits in to the
      overall goal of understanding AD.

PMID- 23133827
TI  - Zr(H2O)2EDTA modulated luminescent carbon dots as fluorescent probes for fluoride
      detection.
AB  - A novel fluorescent probe (Zr(CDs-COO)(2)EDTA) has been designed for fluoride ion
      (F(-)) content detection based on the competitive ligand reactions carried out
      between the carboxylate groups (-COOH) on the surface of the luminescent carbon
      dots (CDs) and F(-) coordinated to Zr(H(2)O)(2)EDTA. The strong and stable
      fluorescence signal of this probe was quenched upon the addition of F(-) as a
      result of the formation of the non-fluorescent complex Zr(F)(2)EDTA, due to the
      stronger affinity of F(-) than the -COOH in the CDs to Zr(IV). The fluorescence
      change (DeltaF) in this process was linear with respect to the content of F(-),
      ranging from 0.10 MUM to 10 MUM. The probe has been applied to F(-) detection in
      toothpaste and water samples with satisfactory results. Moreover, the mechanism
      of this Zr(H(2)O)(2)EDTA modulated fluorescent probe for the detection of F(-)
      was also discussed.

PMID- 23133828
TI  - Homogeneous water oxidation catalysts containing a single metal site.
AB  - The recent recognition that a single metal site is capable of mediating the
      multiple electron and proton transfer events associated with water oxidation
      represents a pivotal discovery for the field. This finding has led to a
      remarkable expansion of known synthetic water oxidation catalysts, and has
      provided the means to gain unprecedented insight into the reaction steps involved
      with O-O bond formation. This perspective reflects on the key studies that have
      advanced our understanding of water oxidation catalysis while summarizing
      molecular features that are integral to negotiating this complicated reaction
      pathway with the goal of helping identify new frontiers of discovery for the
      field.

PMID- 23133829
TI  - A 24-Gd nanocapsule with a large magnetocaloric effect.
AB  - Two 24-nuclear lanthanide clusters,  and  were obtained and structurally
      characterized. Magnetic investigations reveal that  exhibits the largest entropy
      change (-DeltaS(m)) of 46.12 J kg(-1) K(-1) for DeltaH = 7 T in all reported
      molecular clusters, and single-molecule magnet behaviour is observed in .

PMID- 23133830
TI  - eLCR: electrochemical detection of single DNA base changes via ligase chain
      reaction.
AB  - Simple, inexpensive and wide-scaled analysis of single DNA base changes ('point
      mutations' which include SNP's, somatic mutations and epigenetic changes) is one
      of the holy grail's of point-of-care diagnostics. Herein, we present eLCR: a
      simple methodology that fuses Ligase Chain Reaction (LCR) with electrochemical
      detection based on DNA-mediated charge transport. LCR generates long and short
      "knife" motifs representing the presence or absence of single DNA base changes,
      which are then detected electrochemically by either methylene blue intercalation
      or horseradish peroxidase labelling.

PMID- 23133831
TI  - A facile approach to synthesize novel oxygen-doped g-C3N4 with superior visible
      light photoreactivity.
AB  - O-doped g-C(3)N(4) was synthesized for the first time by a facile H(2)O(2)
      hydrothermal approach. The O-doping in the g-C(3)N(4) lattice could induce
      intrinsic electronic and band structure modulation, resulting in its absorbance
      edge up to 498 nm and enhanced visible-light photoactivity, consequently.

PMID- 23133832
TI  - Amino acid-bile acid based molecules: extremely narrow surfactant nanotubes
      formed by a phenylalanine-substituted cholic acid.
AB  - An amino acid-substituted bile acid forms tubular aggregates with inner and outer
      diameters of about 3 and 6 nm. The diameters are unusually small for surfactant
      self-assembled tubes. The results enhance the spectrum of applications of
      supramolecular tubules and open up possibilities for investigating a novel class
      of biological amphiphiles.

PMID- 23133833
TI  - Measurement of the base number of DNA using a special calliper made of a split G
      quadruplex.
AB  - A special DNA calliper made of a split G-quadruplex was constructed to measure
      the length of DNA in a single-digit base number range between two selected
      sequences. The enhanced fluorescence of PPIX changed with the distance between
      two G-rich segments.

PMID- 23133834
TI  - A colorimetric logic gate based on free gold nanoparticles and the coordination
      strategy between melamine and mercury ions.
AB  - A colorimetric logic gate based on free gold nanoparticles is presented with
      melamine and Hg(2+), as well as its colorimetric detection of Hg(2+) with good
      selectivity and sensitivity.

PMID- 23133835
TI  - A straightforward access to photochromic diarylethene derivatives via palladium
      catalysed direct heteroarylation of 1,2-dichloroperfluorocyclopentene.
AB  - A novel and efficient palladium-catalysed direct di-heteroarylation of 1,2
      dichloroperfluorocyclopentene with a variety of heteroarenes is reported, giving
      rise to 1,2-di(heteroaryl)ylperfluorocyclopentene photochromic compounds. The
      reaction proceeds with thiazoles, thiophenes or furan derivatives and tolerates
      various substituents.

PMID- 23133836
TI  - Reversible binding of nitric oxide to an Fe(III) complex of a tetra-amido
      macrocycle.
AB  - Nitric oxide binds reversibly to the Fe(III) complex of a well-developed tetra
      amido macrocyclic ligand. Reaction with NO results in formation of a species
      consistent with an S = 1 {Fe-NO}(6) ground state as characterized by UV-vis, IR,
      EPR, and Mossbauer spectroscopy. The resultant nitrosyl is labile and dissociates
      readily upon purging with N(2), thus providing a rare example of reversible NO
      binding to non-heme iron.

PMID- 23133837
TI  - Freezing and melting behavior of an octyl beta-D-glucoside-water binary system-
      inhibitory effect of octyl beta-D-glucoside on ice crystal formation.
AB  - Phase transition behavior of lyotropic liquid crystals of an octyl beta-D
      glucoside (OG)-water binary system during ice freezing and melting was studied by
      differential scanning calorimetry (DSC) and polarizing optical microscopy (POM).
      Not the thermotropic, but the lyotropic phase transition due to the change of OG
      concentration during ice freezing and melting was observed. The concentration
      temperature phase diagram of the binary system was constructed. Melting
      temperature of ice, T(m), lyotropic phase transition temperature, T(tr), and
      glass transition temperatures of unfrozen phases in the absence and presence of
      ice, T(g) and T(g)', were shown in the phase diagram. The phase diagram indicated
      that the OG aqueous system was concentrated to ca. 90-92 wt% by ice freezing and
      exhibited glass transition at T(g)'. An observation of the concentration-gradient
      specimen by the cryo-POM showed the evidence of the inhibitory effects of OG on
      nucleation and growth of ice crystals in the extremely high OG concentration
      system in which the lamellar liquid crystalline phase was formed. This study
      provided the importance of the influence of concentration change by ice freezing
      on the behaviour of the sugar-based surfactant-water system under low temperature
      conditions.

PMID- 23133838
TI  - Facile synthesis of a platinum-lead oxide nanocomposite catalyst with high
      activity and durability for ethanol electrooxidation.
AB  - Aimed at searching for highly active and stable nano-scale Pt-based catalysts
      that can improve significantly the energy conversion efficiency of direct ethanol
      fuel cells (DEFCs), a novel Pt-PbO(x) nanocomposite (Pt-PbO(x) NC) catalyst with
      a mean size of 3.23 nm was synthesized through a simple wet chemistry method
      without using a surfactant, organometallic precursors and high temperature.
      Electrocatalytic tests demonstrated that the as-prepared Pt-PbO(x) NC catalyst
      possesses a much higher catalytic activity and a longer durability than Pt
      nanoparticles (nm-Pt) and commercial Pt black catalysts for ethanol
      electrooxidation. For instance, Pt-PbO(x) NC showed an onset potential that was
      30 mV and 44 mV less positive, together with a peak current density 1.7 and 2.6
      times higher than those observed for nm-Pt and Pt black catalysts in the cyclic
      voltammogram tests. The ratio of current densities per unit Pt mass on Pt-PbO(x)
      NC, nm-Pt and Pt black catalysts is 27.3 : 3.4 : 1 for the long-term (2 hours)
      chronoamperometric experiments measured at -0.4 V (vs. SCE). In situ FTIR
      spectroscopic studies revealed that the activity of breaking C-C bonds of ethanol
      of the Pt-PbO(x) NC is as high as 5.17 times that of the nm-Pt, which illustrates
      a high efficiency of ethanol oxidation to CO(2) on the as-prepared Pt-PbO(x) NC
      catalyst.

PMID- 23133839
TI  - Proceedings of the 15th European Carbohydrate Symposium, July 3-7, 2012,
      Sorrento, Italy.

PMID- 23133840
TI  - Proceedings and Abstracts of the 6th International Conference on Thrombosis and
      Hemostasis Issues in Cancer, April 20-22, 2012, Bergamo, Italy.

PMID- 23133841
TI  - Food science: A smorgasbord of opportunity.

PMID- 23133842
TI  - Proceedings of the 58th International Congress of Meat Science and Technology
      ICoMST 2012, August 12-17, 2012, Montreal, Canada.

PMID- 23133843
TI  - The Proceedings of the 7th International Meeting on Rapid Responses to Steroid
      Hormones, September 14-17, 2011, Crete, Greece.

PMID- 23133844
TI  - Special issue in tribute to James A. Wilkerson III, MD.

PMID- 23133845
TI  - A special issue in tribute to John F. Oram.

PMID- 23133846
TI  - [Terminal renal failure: increased mortality due to early dialysis?].

PMID- 23133847
TI  - [Risks in atrial fibrillation and simultaneous renal failure].

PMID- 23133848
TI  - [Increased breast cancer risk caused by spironolactone?].

PMID- 23133849
TI  - [EHEC-HUS: which therapeutic strategy was effective?].

PMID- 23133850
TI  - [Liver transplantation in children: new surgical procedures].

PMID- 23133851
TI  - From puppy love to quinquagenarians and beyond!

PMID- 23133852
TI  - Gallstones.  Symptoms usually mean surgery.

PMID- 23133853
TI  - Health tips.  Sickness and grandchild visits.

PMID- 23133854
TI  - Heart benefit of 'good' cholesterol depends on how it occurs.

PMID- 23133855
TI  - Closing in on a melanoma skin cancer vaccine.

PMID- 23133856
TI  - Diabetes complications.  Proactive care a must.

PMID- 23133857
TI  - I was recently diagnosed with type 2 diabetes and am getting used to doing daily
      blood sugar tests and logging my results. Why does my doctor want to do a blood
      sugar test called A1C every few months, too?

PMID- 23133858
TI  - I was diagnosed with heart failure earlier in the year. I've taken steps to
      manage the problem. The disease is stable and I feel good. Still, I'm wondering
      if I should skip our annual ski vacation to Colorado due to the high elevation?

PMID- 23133859
TI  - Fractured rib.  Guarding against complications.

PMID- 23133860
TI  - From research to breakthrough treatments.  Mayo Clinic is a leader in
      translational research.

PMID- 23133861
TI  - Vaginal atrophy.  Managing vaginal dryness and irritation.

PMID- 23133862
TI  - Boning up on calcium and vitamin D.  Do you need supplements to preserve your
      bone health?

PMID- 23133863
TI  - Surviving cancer: steps you can take to guard against recurrence.

PMID- 23133864
TI  - Staying safe on the road.  How to steer clear of driving mishaps.

PMID- 23133865
TI  - Preventing kidney stones.

PMID- 23133866
TI  - How to avoid drug errors.  Making a safe transition from hospital to home.

PMID- 23133867
TI  - Whenever I eat wheat products, I get abdominal pain and bloating.  Could it be
      celiac disease?

PMID- 23133868
TI  - How do clinical trials for drugs work?

PMID- 23133869
TI  - What is Charcot foot?

PMID- 23133870
TI  - [On a case of serous cystadenoma causing obstructive jaundice].

PMID- 23133871
TI  - [Q & A. A case of anemia and raised lesions of the stomach].

PMID- 23133872
TI  - [On hepatocarcinogenesis from the viewpoint of metabolic disorders. Discussion].

PMID- 23133873
TI  - [Surgical outcome of biliary tract cancer with neoadjuvant chemotherapy].

PMID- 23133874
TI  - [The development of chemotherapy to unresectable advanced biliary tract cancer].

PMID- 23133875
TI  - Pituitary adenoma.

PMID- 23133876
TI  - Tribute to Tom Rowland.

PMID- 23133877
TI  - Pediatric exercise science: passing the baton.

PMID- 23133878
TI  - [Practical issues in revision of radiation hazards prevention regulations of
      hospitals regarding radioactivation of medical accelerators; accompanying the
      revision of law concerning prevention from radiation hazards due to
      radioisotopes, etc., which come into force on April 1, 2012 in Japan].

PMID- 23133879
TI  - [Q & A. A tumor of the uncinate process of the pancreas with skin lesions].

PMID- 23133880
TI  - [The dilemma of discharge medication. A multicentre cohort study on distribution
      of discharge medication and counseling by the hospital pharmacist in comparison
      to current practice].
AB  - BACKGROUND: Today medication gaps are inevitable at discharge from the hospital
      and patients are insufficiently educated about their medication. METHODS: The
      rate of medication gaps and extent and quality of medication counseling were
      investigated in a prospective comparative study at five different hospitals. In a
      consecutive manner 847 patients were observed using current practice and 618
      patients with a hospital pharmacist involved. Perception of patients, their
      general practitioners (GP) and community pharmacists with the different discharge
      procedures was analyzed by meansof questionnaires. RESULTS: Using current
      practice 24% of patients missed newly prescribed drugs at discharge. Medication
      gaps occurred according to patients'or GPs'reports in 10% or 22% of patients,
      respectively. 12% of patients were neither educated in the hospital nor in
      private setting about their medication. 22% of patients were not or only
      partially satisfied with the information received. Patient education, supported
      by a medication schedule and distribution of discharge medication by hospital
      pharmacists proved to be feasible and beneficial for patients and GPs. Medication
      gaps were significantly reduced to 4%. All patients received medication
      counseling at discharge and quality of education significantlyimproved.
      CONCLUSION: Distribution of discharge medication and counseling of patients bya
      hospital pharmacist are suitable measures in order to bridge medication and
      information gaps. Changes in healthcare legislation are necessary in order to
      implement the hospital pharmacy service.

PMID- 23133881
TI  - [Effects of headers on coagulation parameters].
AB  - BACKGROUND: This paper is testing the hypothesis whether headers can cause micro
      traumata which can be verified in lab test. METHOD: The study examined micro
      traumatic effects of headers for a sample of 22 soccer players by the means of
      blood tests. In the test arrangement, two probands intensively exchanged headers
      with a standard football (according to official regulations of the German
      Football Association) fora period of eight minutes.The average number of ball
      exchanges per series amounted to around 401 headers for each pair. The effects
      were measured by selected coagulation parameters. RESULTS: The results showed
      significant differences in the concentration of leucocytes and thrombocytes. The
      variance analysis of coagulation parameters revealed no significant change for
      fibrinogen concentration, INR and Quick. By contrast, the reduction of aPTT after
      the headers was significant. CONCLUSION: As for an interpretation of these
      results, the observed increase of the parameters may be characterised as a
      reaction to stress. The increase of thrombocytes could be seen as response of the
      corpuscular coagulation system to traumatisation. As aPTT is significantly
      reduced post intervention, this furthermore reflects an activation of the plasmic
      coagulation system induced by trauma.

PMID- 23133882
TI  - [Venous ulcer is an ischemic wound!].

PMID- 23133883
TI  - [Generalized anxiety disorder in primary care. Patterns of healthcare utilization
      in Germany].
AB  - BACKGROUND: Generalized Anxiety Disorder (GAD) has been described in community
      studies as a frequent and costly high utilizer group in the primary care sector.
      Administrative data supporting this observation are lacking so far. METHODS: This
      paper reports utilization and prescription data of a nationally representative
      sample of over 900 primary care physicians, over 75 million prescriptions and 12
      month utilization and prescription patterns of n = 3,340 GAD patients.These are
      compared to a matched control group without GAD, and without any anxiety or
      depressive disorder (n = 3,340). RESULTS: GAD patients in comparison to the
      matched controls revealed: (1) 2-fold increased primary care, (2) almost 3-fold
      specialist referrals, (3) almost 2-fold increased overall prescription rates, and
      (4) 3.5-fold increased sick certificates. However, only 58.3% of GAD patients
      were treated with any psychotropic medication. DISCUSSION: The data of this
      administrative-epidemiological cohort study support strongly the view that GAD
      ranks among the most costly high utilizer patient group in primary care in
      Germany. However, they are rarely treated according to evidence-based guidelines.
      The paper discusses these findings by suggesting that comorbid conditions might
      be a barrier for primary care physicians to initiate existing, more appropriate
      state of the art treatments.

PMID- 23133884
TI  - [Tapentadol prolonged release for severe chronic pain. Results of a non
      interventional study involving general practitioners and internists].
AB  - STUDY OBJECTIVE: This prospective, non-interventional study involving general
      practitioners and internists in Germany investigated the administration of
      tapentadol prolonged release (Palexia retard) for the treatment of severe chronic
      pain in routineclinical practice over a 3-month observation period. METHODS:
      Collected data included tapentadol PR dosage, previous and concomitant analgesic
      treatment, pain intensity, sleep and quality of life parameters, and tolerability
      of tapentadol PR. Effectiveness was analyzed for 3134 patients; additionally, a
      subgroup analysis was performed in 1331 patients with WHO III pretreatment.
      RESULTS: A total of 97.8% of all patients received analgesic long-term
      pretreatment, 42.5% of those strong opioids. Switching to tapentadol PR resulted
      in a mean pain reduction of 3.9 points from 7.0 +/- 1.5 at baseline to 3.1 +/-
      1.8 at end of observation (NRS-11, 11-point pain scale; descriptive p value < or
      = 0.001); 72.1% of patients experienced a clinically relevant pain relief of > or
      = 50% at end of observation. A total of 89.4% of the patients attained either
      their intended pain reduction and/or an additional individual treatment goal at
      end of observation; both were established at start of tapentadol PR treatment.
      This was accompanied by a significant decrease in pain-related impairments of
      daily activities and an improvement in quality of life (descriptive p value < or
      = 0.001) with an overall good tolerability of tapentadol PR. In particular, good
      effectiveness of tapentadol PR treatment was reported for various pain
      indications in patients who had already previously been treated with strong
      opioids. A clinically relevant pain reduction > or = 50% was achieved in 67.2% of
      these patients. CONCLUSIONS: Tapentadol PR can be considered an alternative
      therapy to classical opioids for the treatment of severe chronic pain.
      Particularly for severe chronic pain requiring long-term medication, a reduction
      of common opioid side-effects with tapentadol PR therapy could contribute to
      better patient compliance.

PMID- 23133885
TI  - [Does the Physician's lack of scientific rigor cost him?].

PMID- 23133886
TI  - [Surgery for severe aspirations].
AB  - Severe dysphagia resulting in repeated aspirations and pneumonia are difficult to
      treat with swallowing therapy and surgical treatment is often required. Our study
      retrospectively reviews our experience with 19 such cases operated by laryngeal
      suspension and laryngotracheal separation. Restoration of oral nutrition was
      possible in 45% of laryngeal suspension cases and in 75% of laryngotracheal
      separation operations. These surgical techniques prevent severe aspirations while
      conserving phonation, contrarily to total laryngectomy. Tracheocutaneous fistulas
      were frequent, especially after radiation, implying that the surgical technique
      should be modified in the future.

PMID- 23133887
TI  - [Peripheral tuberculous lymphadenitis: diagnosis and management].
AB  - Tuberculous lymphadenitis is a frequent presentation of extrapulmonary
      tuberculosis. It corresponds to about 10% of tuberculosis cases in adults in
      developed countries, on the rise because of HIV, migrants and immunosuppressive
      therapy. The clinical diagnosis is often difficult and differential diagnosis is
      extensive. The patient presents with a history of painless swelling of one or a
      group of cervical lymph nodes. The mass may be present for 3 weeks to 8 months
      before the first consultation. The treatment of choice is an oral
      antimycobacterial treatment and is not surgical. This article reviews the
      specific clinical manifestations, diagnositc tools and treatment of tuberculous
      lymphadenitis through two cases.

PMID- 23133888
TI  - [Ear reconstruction in case of microtia].
AB  - Microtia is a uncommon pathology that is defined by a hypoplasia of the pinna.
      Multiple reconstructives surgeries have been developed. Nowadays, autologous rib
      cartilage reconstruction and Medpor implant reconstruction are the most widely
      used techniques. The authors present these two alternatives that significantly
      improve the quality of life of young patients with this visible abnormality.

PMID- 23133889
TI  - [Odd stories of patients suffering from Meniere's disease].
AB  - The cause of Meniere's disease is unknown. The postmortem examination of the
      temporal bone reveals an "endolymphatic hydrops" of the inner ear. Classically,
      patients describe episodes of vertigo, fluctuations of hearing and tinnitus. But
      some report "strange stories" that deserve doctor's attention. This article
      explains why their history (as those suffering from any other vestibular
      disorder) is often particular, to recall the few knowledge of the disease, how
      the endolymphatic hydrops was considered as the cause of the disorder, while it
      is rather an epiphenomenon, and to show how one can believe, wrongly, that a
      therapy is efficient after a study that seems however at first correctly
      performed.

PMID- 23133890
TI  - [Surgical treatment of benign paroxysmal positional vertigo].
AB  - Benign paroxysmal positional vertigo (BPPV) is a common disorder that presents to
      the general practitioner. This condition represents one of the most common causes
      of peripheral vertigo. The diagnosis is made on clinical grounds. The treatment
      relies on repositioning maneuvers with relief of symptoms that occur in a few
      weeks in the majority of the cases. Rarely, patients are incapacitated by
      persistent or recurrent BPPV despite multiple repositioning maneuvers. In these
      cases, surgical therapies are available which provide excellent results.

PMID- 23133891
TI  - [Causal relationship: and if "yes", and if "not"... on basis of which
      criterias?].
AB  - A woman was referred to us 4 days after the sudden onset of continuous rotatory
      vertigo. The diagnosis of a left vestibular neuronitis was made. During the
      investigations, a meningioma of the contralateral posterior fossa was discovered.
      Is there any relationship between the two disorders? The etiology of peripheral
      vestibular disorders remains poorly understood in most cases. Anomalies of cells
      surrounding the sensory organs have been demonstrated in post-mortem examination
      of the inner ear of patients with a vestibular deficit that could be caused by a
      "biological stress". Therefore there may be a link between left vestibular
      deficit and the mass of the right posterior fossa, considered as a fortuitous
      discovery, at first.

PMID- 23133892
TI  - [I am old and sick, therefore I "exit"?].
AB  - One hundred seventy patients (average age 79.9 years) with preserved cognitive
      faculties agreed to complete a questionnaire on the costs caused by their health
      conditions, the guilt they feel due to these costs, and their eventual resort to
      the Exit association. 48% answered that health care cost too much to the
      community, 10% reported feeling guilty about the potential costs generated by a
      consultation with their physician. 98 patients knew about the Exit association:
      26% considered that resorting to Exit was a way to reduce health costs, 30% a way
      to avoid being an economic burden to their family and 34% a way to die with
      dignity. Our results indicate that economic pressure on medical costs is a source
      of guilt for older citizens, so much so that one in 10 patients considers
      resorting to assisted sucide for fear of costing too much to the community.

PMID- 23133893
TI  - [Why am I forbidden from dosing my PSA?].

PMID- 23133894
TI  - [Two swedish maternal uteri, therapeutic and transient].

PMID- 23133895
TI  - [Dr. Ernesto Guevara de la Serna].

PMID- 23133896
TI  - [Desire versus satisfaction].

PMID- 23133897
TI  - [Overprotected autonomy].

PMID- 23133898
TI  - [Preventing falls in people with cognitive impairment].
AB  - The residence Eleusis in Poissy (78) is a nursing home for dependent elderly
      people, it specialises in the care of people with severe cognitive impairment. It
      offers weekly workshops in fall prevention. This is geared towards motor,
      cognitive and behavioural components in order to take into account the person as
      a whole.

PMID- 23133899
TI  - [An innovative approach to support for the elderly].
AB  - In order to improve the care conditions of elderly patients at the Saint-Nicolas
      hospital in Angers, two health care techniques have been developed: the diffusion
      of essential oils and a relaxing massage. We have evaluated their effect on
      patients and their caregivers and a certain number of advantages have been
      demonstrated.

PMID- 23133900
TI  - [Mini Nutritional Assessment: a reproducibility study for the elderly].
AB  - The Mini Nutritional Assessment (MNA), the most used scale for detecting
      undernutrition in clinical practice, has been validated in the hospital setting.
      We have evaluated its reproducibility in a French nursing home for dependent
      elderly people. It is globally acceptable, but some items should be more
      standardized.

PMID- 23133901
TI  - [I discuss the difficulties of returning home for the handicapped patient].

PMID- 23133902
TI  - [Beneficence and social ties in geriatrics].

PMID- 23133903
TI  - [Sleep in the elderly].

PMID- 23133904
TI  - [Sleep in question].
AB  - It is important to differentiate the effects of aging on sleep systems from the
      effects of medical illnesses. The health care team, especially the night team,
      plays an essential role in the identification of sleep disorders and in setting
      up strategies for better management of nocturnal difficulties.

PMID- 23133905
TI  - [Fostering an environment favorable to the sleep-wake rhythm].
AB  - Health care teams in nursing homes for the elderly, as well as home care workers
      are faced with patients whose sleep is sometimes disturbed. Understanding sleep
      disorders and the sleep-wake cycle functioning may help improve patients rest. An
      action on the environment and rituals can help in the return to peaceful nights.

PMID- 23133906
TI  - [Sleep apnea syndrome and cognitive impairment].
AB  - The sleep apnoea syndrome is a common disorder, unrecognised in the elderly.
      Several studies have shown that it can cause or exacerbate cognitive impairment,
      mainly related to attention, memory and learning and adaptation abilities.
      However, continuous positive airway pressure treatment appears to be effective on
      these cognitive disorders, including in elderly patients.Accordingly, the sleep
      apnoea syndrome can be a conceivable diagnostic as part of the cognitive
      deterioration check-up in elderly patients.

PMID- 23133907
TI  - [Their own bedroom in their own home].
AB  - The elderly, choose one room and one only in their apartment or house in order to
      economise. By finding new landmarks, preserving memories and objects to feel
      good, the elderly person creates rituals that promote rest, enjoyable past-times
      and sleep too ward off the anxieties of the night.

PMID- 23133908
TI  - [Night support in special care units].
AB  - People with Alzheimer's disease and related disorders in nursing homes are also
      subject to sleep disorders. An in-depth study was therefore carried out to
      install a familiar setting that is based on the architectural environment and on
      specific support taking into account the size of healthcare teams.

PMID- 23133909
TI  - [Mobile night staff].
AB  - The elderly who need home care, may if they wish benefit from a night time home
      visit through an Association in Nantes.This assistance is sometimes valuable in
      order to prepare for a peaceful night. Feedback on a local initiative.

PMID- 23133910
TI  - [Sleep in the elderly. Bibliography].

PMID- 23133911
TI  - [Prevention of low back pain].

PMID- 23133912
TI  - [Croatian Society for Clinical Cytology guidelines for thyroid cytology].
AB  - The main purpose of thyroid FNA (fine needle aspiration) is to separate malignant
      and possibly malignant nodules from benign thyroid lesions. Every patient with
      thyroid nodule is a candidate for FNA. Before a decision to perform an FNA, a
      complete history, a physical examination directed to the thyroid and cervical
      lymph nodes, a serum thyrotropin level, and thyroid ultrasound should be
      obtained. Thyroid lesion with a maximum diameter greater than 1.5 cm or nodule of
      any size with sonographically suspicious features is an indication for FNA.
      Ultrasound-guided FNA of the thyroid is recommended. The requisition form that
      accompanies FNA should contain the identifying data, location and size of the
      nodule, and relevant laboratory and clinical data. FNA diagnosis of thyroid
      disease is a clinicocytologic diagnosis, and correlation with clinical findings
      is mandatory for success. Thyroid FNA classification scheme consists of a four
      diagnostic categories according to the risk of malignancy: benign lesions,
      indeterminate lesions according to malignancy, malignant tumors, and non
      diagnostic. Ancillary studies (immunocytochemistry, RT-PCR, flow cytometry) are
      usually helpful in borderline cases.

PMID- 23133913
TI  - [Anxiety and depression in oncology patients in the Mostar University Clinical
      Hospital].
AB  - OBJECTIVE: To determine the degree of anxiety and depression in patients
      hospitalized at the Department of Oncology of the Mostar University Clinical
      Hospital and the relationship between the degree of anxiety and depression, sex,
      marital status, age, and education of the patients. PATIENTS AND METHODS: The
      study included 160 patients who were divided into two groups: a test and a
      control group. A patient from the test group was assigned a patient from the
      control group according to his/her age, gender, education level and marital
      status. The study population consisted of 80 patients who were treated at the
      Department of Oncology of the Mostar University Clinical Hospital from January 1,
      2010 to March 31, 2010. The control group consisted of 80 patients who were
      admitted via the Family Medicine Office of the Mostar Community Health Center
      from March 1, 2010 to March 31, 2010. The Beck's Anxiety and Depression scale was
      used. The appropriate statistical methods were used to test the collected data.
      RESULTS: Patients hospitalized at the Department of Oncology had a greater degree
      of depression than the control group (exact test, P<0.001). A significant
      difference in the level of anxiety between the test and control groups was not
      found (exact test, P=0.143). A mild degree of anxiety was found in the cancer
      patients older than 60 and a high level of anxiety in the group aged 25-40 (exact
      test, P<0.001) and in highly educated patients (exact test, P=0.024). The
      research showed that the cancer patients from the younger age group had higher
      levels of depression (exact test, P<0.001). By comparing the degree of anxiety to
      the age in the control group, statistically significant difference was not found,
      so the highest level of anxiety was found in the patients aged between 41 and 60
      (exact test, P<0.001). It was determined that a higher percentage of women (exact
      test, P=0.034) and patients over 60 years old (exact test, P=0.006) in the
      control group were more depressed. CONCLUSION: Although a statistically higher
      level of depression was determined for the test group patients, a statistically
      significant difference in the levels of anxiety between test and control groups
      was not found.

PMID- 23133914
TI  - [Idiopathic eosinophilic pleural effusion--case report].
AB  - Eosinophilic pleural effusion (EPE) is defined as exudative effusion that
      contains at least 10% eosinophils. The most common conditions associated with EPE
      are malignancy, infections, post-traumatic and post-surgical conditions,
      hypersensitivity, systemic autoimmune diseases, congestive heart failure,
      cirrhosis, pulmonary embolus, asbestosis and drug induced EPE. Pleural effusion
      accompanying autoimmune diseases is most common in patients with systemic lupus
      erythematosus, rheumatoid arthritis, howewer it rarely occurs in patients with
      progressive systemic sclerosis and polymiositis. EPE has rarely been reported in
      association with Churg Strauss syndrome. In about 14-25% of patients EPE can be
      defined as idiopathic when diagnostic procedures failed to identify the etiology.
      Treatment of EPE is based on the treatment of primary disease and with idiopathic
      form a good answer is reached using glucocorticoids. In this case report we
      presented the patient with idiopathic eosinophilic pleural effusion where in
      diagnostic procedures we excluded other diseases or conditions in which EPE can
      be shown, and with applied therapy with methylprednisolone we achieved excellent
      clinical response and final healing.

PMID- 23133915
TI  - [Genetic background of aseptic instability after total hip arthroplasty].
AB  - Total hip arthroplasty (THA) has dramatically improved the treatment of an entire
      range of hip joint diseases. On the other hand, however, it has favored the
      development of a new disease - periprosthetic osteolysis with a consequent
      instability of THA. Aseptic instability is the major late complication of THA and
      the main reason of its malfunction. Molecular and cellular mechanisms of this
      complication have been thoroughly studied. The importance of prosthetic materials
      and design have been clearly demonstrated. However, existence of individual
      susceptibility to development of this complication that is determined neither by
      endoprothesis properties nor by demographic or morbidity characteristics of a
      patient has also been recognized. In the recent years, several smaller studies
      have tried to define the "genetic background of the individual susceptibility"
      towards the development of aseptic instability. All these studies followed the
      same logic - they searched for a link between the complication and genes coding
      for mediators of inflammation and/or bone remodeling, particularly those with
      known polymorphisms that influence expression/activity. Several associations have
      been found indicating, at least theoretically, a potential of developing a system
      of relatively reliable individual risk prediction, which in turn could result in
      individualized choice of prosthetic material, postoperative therapy programs and
      medication therapy. However, this research is at an early stage and future
      efforts should be focused on a) identification of genetic markers - reliable
      predictors and b) identification of functional links between particular genetic
      markers and aseptic instability. It is impossible to meet these goals without
      application of techniques of proteomic analysis.

PMID- 23133916
TI  - [Ligament which deserves attention--medial patellofemoral ligament].
AB  - There has been increasing interest in investigating the medial patellofemoral
      ligament (MPFL) during the last fifteen years. This is due to the recognition of
      the MPFL as the primary static soft-tissue restraint to lateral patellar
      displacement and the association of MPFL injury with primary traumatic patellar
      dislocation. The MPFL often heals poorly and thus rarely regains its full
      function. Numerous surgical techniques have been described for reconstruction of
      this important structure. This paper reviews the relevant anatomy and
      biomechanics, published reconstruction options, and describes the surgical
      technique performed at our institution--that of using a quadriceps autograft to
      reconstruct the MPFL.

PMID- 23133917
TI  - [Placebo in the pain treatment].
AB  - Use of medical preparations having no specific pharmacological activity or dummy
      procedures administered to patients is known as placebo. Such maneuvers are
      important in the pain treatment and clinical studies investigating pain
      mechanisms. Several recent studies have shown that placebo treatment produces
      measurable psychophysiological effects, characterized by changes in specific
      brain functions and decreased subjective pain perception. This article reviews
      changes observed in placebo analgesia, its intensity as compared to active
      compounds, and principal problems observed during the placebo treatment and in
      clinical trials.

PMID- 23133918
TI  - [Matthias Flacius Illyricus, the younger, professor philosophiae et logicae
      aristotelis and professor of the practical medicine].
AB  - The aim of this paper is to offer some new information on the life and work of
      Matthias Flacius Illiricus the Younger, especially concerning his activity as a
      medical doctor and university professor. According to our present knowledge, he
      published 17 of his writings during his lifetime. Matthias Flacius the Younger
      was born on September 12, 1547 in Braunschweig. His mother Elisabeth had 11 more
      children with Matthias Flacius the Elder.When Flacius the Younger was 15 (in
      1562), his father sent him to Strassburg to study philosophy. According to some
      scholars (Waltraut Wienke, 2001), Flacius the Younger arrived to Rostock in
      August 1572 and was granted the title of magister philosophiae on April 1, 1574.
      According to the sources, that very year he was enrolled at the Faculty of
      Medicine in Rostock. On April 27, 1579 he was mentioned as lecturing at the
      Faculty of Philosophy, where he became Philosophiae & Logicae Aristotelis doctor
      in 1580. It is interesting that only a year later on September 23, 1581, when he
      was 33 years old, he became Doctor Medicinae by defending a dissertation entitled
      "De cattarrho; ward darauf zum Dr Med prom". In 1592 he exchanged his position at
      the Philosophy Chair in Rostock for the medical one, becoming a professor of
      Practical Medicine. Matthias Flacius the Younger died on April 27, 1593, when he
      was 46 years old.

PMID- 23133919
TI  - [Beware of therapeutic and/or diagnostic enthusiasm].

PMID- 23133920
TI  - [Venous thromboembolism, thrombophilia, and antithrombotic therapy in pregnancy
      in the light of the new guidelines].

PMID- 23133921
TI  - [Epidemiology of hematologic malignancy in Japan].

PMID- 23133923
TI  - [Natural history of leukemia].

PMID- 23133922
TI  - [Epidemiology of hematological malignancies around the world].

PMID- 23133924
TI  - [Epidemiology of adult T-cell leukemia and HTLV-1 infection--toward the
      eradication of HTLV-1 infectious diseases].

PMID- 23133925
TI  - [Carcinogenic chemicals and risk of hematopoietic neoplasms].

PMID- 23133926
TI  - [Increased risks for hematological neoplasms induced by virus infection].

PMID- 23133927
TI  - [Risk of carcinogenesis caused by infection and inflammation].

PMID- 23133928
TI  - [Cancer risk by radiation].

PMID- 23133929
TI  - [Chromosomes and genes].

PMID- 23133930
TI  - [Molecules of signal transduction].

PMID- 23133931
TI  - [Transcriptional regulation].

PMID- 23133932
TI  - [Cell cycle].

PMID- 23133933
TI  - [Epigenetics].

PMID- 23133934
TI  - [Genomic instability in leukemia].

PMID- 23133935
TI  - [Proteasome oncology: pioneer a new field in drug development].

PMID- 23133936
TI  - [Genetic and cytogenetic abnormalities in leukemia].

PMID- 23133937
TI  - [Genetic and chromosomal abnormalities in myelodysplastic syndrome].

PMID- 23133938
TI  - [Genome-wide analysis of AML and MDS].

PMID- 23133939
TI  - [Molecular pathogenesis of non-Hodgkin's lymphoma].

PMID- 23133940
TI  - [Genetic and cytogenetic abnormalities of multiple myeloma].

PMID- 23133941
TI  - [Regulation of hematopoietic stem cells in niche signaling].

PMID- 23133942
TI  - [Leukemia stem cells: current understanding and future directions].

PMID- 23133943
TI  - [Utilization of the ES/iPS cell technology for hematopoietic stem cell
      transplantation].

PMID- 23133944
TI  - [Cytokines which are essential for hematopoiesis].

PMID- 23133945
TI  - [Recent advances in the model animals for hematopoietic tumors].

PMID- 23133946
TI  - [Blood and bone marrow examinations: morphology].

PMID- 23133947
TI  - [Cell surface markers].

PMID- 23133948
TI  - [Tumor markers in hematological malignancies].

PMID- 23133949
TI  - [Chromosome analysis].

PMID- 23133950
TI  - [Molecular diagnostics].

PMID- 23133951
TI  - [Pathological diagnosis].

PMID- 23133952
TI  - [Clinical diagnostic imaging (including FDG-PET/CT)].

PMID- 23133953
TI  - [Chemotherapy].

PMID- 23133954
TI  - [Differentiation--inducing therapy].

PMID- 23133955
TI  - [Molecularly target therapy].

PMID- 23133956
TI  - [Monoclonal antibody therapy in hematological malignancies].

PMID- 23133957
TI  - [Radiation therapy for hematopoietic malignant diseases].

PMID- 23133958
TI  - [Hematopoietic stem cell transplantation].

PMID- 23133959
TI  - [Immunotherapy].

PMID- 23133960
TI  - [Gene therapy].

PMID- 23133961
TI  - [Transfusion reaction and HLA antibodies].

PMID- 23133962
TI  - [Management of bacterial infection].

PMID- 23133963
TI  - [Management of invasive fungal infection].

PMID- 23133964
TI  - [Management of viral infection in patients with hematological malignancies].

PMID- 23133965
TI  - [Pathogenesis and treatment of graft-versus-host disease].

PMID- 23133966
TI  - [Clinical management of tumor lysis syndrome].

PMID- 23133967
TI  - [Cell therapy].

PMID- 23133968
TI  - [Cytokine therapy for hematological malignancies].

PMID- 23133969
TI  - [Classification from FAB to WHO in myeloid malignancies].

PMID- 23133970
TI  - [Pathogenesis and pathophysiology of chronic myeloid leukemia in chronic phase].

PMID- 23133971
TI  - [Treatment for de novo chronic myeloid leukemia in chronic phase].

PMID- 23133972
TI  - [Treatment of imatinib-intolerant or -resistant CML patients].

PMID- 23133973
TI  - [Molecular pathogenesis and treatment of CML in accelerated phase and blast
      crisis].

PMID- 23133974
TI  - [Pathogenesis and treatment of polycythemia vera].

PMID- 23133975
TI  - [Molecular pathology and treatment for primary myelofibrosis].

PMID- 23133976
TI  - [Essential thrombocythemia: molecular pathophysiology and treatment].

PMID- 23133977
TI  - [Eosinophilic disorders--etiology, pathology and treatment].

PMID- 23133978
TI  - [Pathogenesis, diagnosis and treatment of mastocytosis].

PMID- 23133979
TI  - [The classification and therapy of myelodysplastic/myeloproliferative neoplasms
      (MDS/MPN)].

PMID- 23133980
TI  - [Pathogenesis of myelodysplastic syndromes].

PMID- 23133981
TI  - [Classification of myelodysplastic syndromes].

PMID- 23133982
TI  - [Prognostic factors of myelodysplastic syndromes].

PMID- 23133983
TI  - [5q--syndrome, MDS with isolated del(5q)].

PMID- 23133984
TI  - [Treatment of myelodysplastic syndromes (MDS)].

PMID- 23133985
TI  - [Indication and outcomes of hematopoietic stem cell transplantation for MDS].

PMID- 23133986
TI  - [Pathogenesis of acute myeloid leukemia].

PMID- 23133987
TI  - [Classification of acute myeloid leukemia].

PMID- 23133988
TI  - [Prognostic factors of acute myeloid leukemia].

PMID- 23133989
TI  - [Current chemotherapeutic approaches in acute myeloid leukemia].

PMID- 23133990
TI  - [Salvage therapy for relapsed and refractory acute myeloid leukemia].

PMID- 23133991
TI  - [Pathogenesis of acute promyelocytic leukemia].

PMID- 23133992
TI  - [Treatment of previously untreated acute promyelocytic leukemia].

PMID- 23133993
TI  - [Management of relapsed acute promyelocytic leukemia].

PMID- 23133994
TI  - [Classification of lymphoid malignancy: from REAL to WHO].

PMID- 23133995
TI  - [Pathology of acute lymphoblastic leukemia].

PMID- 23133996
TI  - [Classification of acute lymphoblastic leukemia].

PMID- 23133997
TI  - [Prognostic factors in adult acute lymphoblastic leukemia].

PMID- 23133998
TI  - [Chemotherapy and hematopoietic stem cell transplantation for acute lymphoblastic
      leukemia].

PMID- 23133999
TI  - [Salvage therapy for primary refractory and relapsed adult acute lymphoblastic
      leukemia].

PMID- 23134000
TI  - [Management of pH-positive acute lymphoblastic leukemia].

PMID- 23134001
TI  - [Pathogenesis, pathophysiology and treatment of chronic lymphocytic leukemia].

PMID- 23134002
TI  - [Pathogenesis and treatment of follicular lymphoma].

PMID- 23134003
TI  - [Etiology, clinical features, and treatment strategies of extranodal marginal
      zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma)].

PMID- 23134004
TI  - [Clinical manifestation, pathologic features and treatment of mantle cell
      lymphoma].

PMID- 23134005
TI  - [Classification of diffuse large B-cell lymphoma].

PMID- 23134006
TI  - [Initial treatment of diffuse large B-cell lymphoma].

PMID- 23134007
TI  - [Treatment of patients with relapsed or refractory diffuse large B-cell
      lymphoma].

PMID- 23134008
TI  - [Diagnosis and treatment for Burkitt lymphoma].

PMID- 23134010
TI  - [Diagnosis and treatment of angioimmunoblastic T-cell lymphoma].

PMID- 23134009
TI  - [Diagnosis and treatment of peripheral T-cell lymphoma].

PMID- 23134011
TI  - [Diagnosis and treatment of adult T-cell leukemia-lymphoma (ATL)].

PMID- 23134012
TI  - [Diagnosis and treatment for cutaneous T-cell lymphomas].

PMID- 23134013
TI  - [Diagnosis and treatment of NK/T-cell lymphoma].

PMID- 23134014
TI  - [Diagnosis and treatments of aggressive NK-cell leukemia].

PMID- 23134015
TI  - [Classification and clinical staging of Hodgkin lymphoma].

PMID- 23134016
TI  - [Diagnosis and treatment of nodular lymphocyte predominant Hodgkin lymphoma].

PMID- 23134017
TI  - [Diagnosis and treatment of classical Hodgkin lymphoma].

PMID- 23134018
TI  - [Molecular biology of myeloma].

PMID- 23134019
TI  - [Diagnosis and prognostic factors in patients with multiple myeloma].

PMID- 23134020
TI  - [Initial therapy for multiple myeloma].

PMID- 23134021
TI  - [Treatment of refractory and relapsed multiple myeloma].

PMID- 23134022
TI  - [Integrated supportive therapy for multiple myeloma-bone disease treatment,
      myeloma kidney treatment, cryotherapy, nutrition support team].

PMID- 23134023
TI  - [Diagnosis and treatment for plasma cell leukemia].

PMID- 23134024
TI  - [Diagnosis and treatment of Waldenstrom macroglobulinemia].

PMID- 23134025
TI  - [Classification and characteristics of acute leukemia in children].

PMID- 23134026
TI  - [Acute lymphoblastic leukemia (ALL)].

PMID- 23134027
TI  - [Acute myelogenous leukemia and chronic myelogenous leukemia in children].

PMID- 23134028
TI  - [Myelodysplastic syndrome in childhood and juvenile myelomonocytic leukemia].

PMID- 23134029
TI  - [Transient myeloproliferative disorder in Down syndrome].

PMID- 23134030
TI  - [EBV-positive T/NK lymphoproliferative disease in childhood].

PMID- 23134031
TI  - [Therapy-related myeloid neoplasms].

PMID- 23134032
TI  - [Treatment strategy for intravascular large B-cell lymphoma].

PMID- 23134033
TI  - [Immunodeficiency related malignant lymphoma].

PMID- 23134035
TI  - [Measurement of minimal residual disease and its implication].

PMID- 23134034
TI  - [Current development of new drugs in malignant lymphoma].

PMID- 23134036
TI  - [Treatment of leukemia in senior adults].

PMID- 23134037
TI  - [Hemophagocytic lymphohistiocytosis].

PMID- 23134038
TI  - [Infection control strategies in hospitalized patients with hematological
      disorders].

PMID- 23134039
TI  - [Psychological distress in survivors who overcome hematological malignancies].

PMID- 23134040
TI  - [Fertility preservation following therapy of hematologic malignancies].

PMID- 23134041
TI  - Searches of hospital patients, their rooms and belongings.

PMID- 23134042
TI  - Assessing the genetic risk for alcohol use disorders.
AB  - The past two decades have witnessed a revolution in the field of genetics which
      has led to a rapid evolution in the tools and techniques available for mapping
      genes that contribute to genetically complex disorders such as alcohol
      dependence. Research in humans and in animal models of human disease has provided
      important new information. Among the most commonly applied approaches used in
      human studies are family studies, case-control studies, and genome-wide
      association studies. Animal models have been aimed at identifying genetic regions
      or individual genes involved in different aspects of alcoholism, using such
      approaches as quantitative trait locus analysis, genome sequencing, knockout
      animals, and other sophisticated molecular genetic techniques. All of these
      approaches have led to the identification of several genes that seem to influence
      the risk for alcohol dependence, which are being further analyzed. Newer studies,
      however, also are attempting to look at the genetic basis of alcoholism at the
      level of the entire genome, moving beyond the study of individual genes toward
      analyses of gene interactions and gene networks in the development of this
      devastating disease.

PMID- 23134043
TI  - Identifying genetic variation for alcohol dependence.
AB  - Researchers are using various strategies to identify the genes that may be
      associated with alcoholism. The initial efforts primarily relied on candidate
      gene and linkage studies; more recently, however, modern advances in genotyping
      have resulted in widespread use of genome-wide association studies for alcohol
      dependence. The key findings of the earlier studies were that variations (i.e.,
      polymorphisms) in the DNA sequences of the genes encoding alcohol dehydrogenase
      1B (i.e., the ADH1B gene), aldehyde dehydrogenase 2 (i.e., the ALDH2 gene), and
      other alcohol-metabolizing enzymes mediate the risk for alcoholism; moreover,
      these polymorphisms also have an impact on the risk of alcohol-related cancers,
      such as esophageal cancer. In addition, a gene encoding one of the receptors for
      the neurotransmitter gamma-aminobutyric acid (GABA) known as GABRA2 seems to have
      a role in the development of alcohol dependence. Genome-wide association studies
      now offer a host of emerging opportunities, as well as challenges, for
      discovering the genetic etiology of alcohol dependence and for unveiling new
      treatment strategies.

PMID- 23134044
TI  - Using genetically engineered animal models in the postgenomic era to understand
      gene function in alcoholism.
AB  - Over the last 50 years, researchers have made substantial progress in identifying
      genetic variations that underlie the complex phenotype of alcoholism. Not much is
      known, however, about how this genetic variation translates into altered
      biological function. Genetic animal models recapitulating specific
      characteristics of the human condition have helped elucidate gene function and
      the genetic basis of disease. In particular, major advances have come from the
      ability to manipulate genes through a variety of genetic technologies that
      provide an unprecedented capacity to determine gene function in the living
      organism and in alcohol-related behaviors. Even newer genetic-engineering
      technologies have given researchers the ability to control when and where a
      specific gene or mutation is activated or deleted, allowing investigators to
      narrow the role of the gene's function to circumscribed neural pathways and
      across development. These technologies are important for all areas of
      neuroscience, and several public and private initiatives are making a new
      generation of genetic-engineering tools available to the scientific community at
      large. Finally, high-throughput "next-generation sequencing" technologies are set
      to rapidly increase knowledge of the genome, epigenome, and transcriptome, which,
      combined with genetically engineered mouse mutants, will enhance insight into
      biological function. All of these resources will provide deeper insight into the
      genetic basis of alcoholism.

PMID- 23134046
TI  - Identifying gene networks underlying the neurobiology of ethanol and alcoholism.
AB  - For complex disorders such as alcoholism, identifying the genes linked to these
      diseases and their specific roles is difficult. Traditional genetic approaches,
      such as genetic association studies (including genome-wide association studies)
      and analyses of quantitative trait loci (QTLs) in both humans and laboratory
      animals already have helped identify some candidate genes. However, because of
      technical obstacles, such as the small impact of any individual gene, these
      approaches only have limited effectiveness in identifying specific genes that
      contribute to complex diseases. The emerging field of systems biology, which
      allows for analyses of entire gene networks, may help researchers better
      elucidate the genetic basis of alcoholism, both in humans and in animal models.
      Such networks can be identified using approaches such as high-throughput
      molecular profiling (e.g., through microarray-based gene expression analyses) or
      strategies referred to as genetical genomics, such as the mapping of expression
      QTLs (eQTLs). Characterization of gene networks can shed light on the biological
      pathways underlying complex traits and provide the functional context for
      identifying those genes that contribute to disease development.

PMID- 23134047
TI  - The impact of gene-environment interaction on alcohol use disorders.
AB  - This article describes three types of gene-environment interactions and the
      challenges inherent in interpreting these interactions. It also reports on what
      is known about gene-environment interactions in the field of alcohol use
      disorders (AUDs). Twin studies of the interaction of genetic and environmental
      influences on AUDs have resulted in relatively consistent findings and have
      suggested general mechanisms for interaction effects. These studies generally
      find that environments that exert more social control (e.g., higher parental
      monitoring, less migratory neighborhoods, etc.) tend to reduce genetic
      influences, whereas other environments allow greater opportunity to express
      genetic predispositions, such as those characterized by more deviant peers and
      greater alcohol availability. Conversely, the gene-environment literature that
      has been developed surrounding specific genes has focused largely on the role of
      stress as a moderator of genetic effects.

PMID- 23134045
TI  - Epigenetics-beyond the genome in alcoholism.
AB  - Genetic and environmental factors play a role in the development of alcoholism.
      Whole-genome expression profiling has highlighted the importance of several genes
      that may contribute to alcohol abuse disorders. In addition, more recent findings
      have added yet another layer of complexity to the overall molecular mechanisms
      involved in a predisposition to alcoholism and addiction by demonstrating that
      processes related to genetic factors that do not manifest as DNA sequence changes
      (i.e., epigenetic processes) play a role. Both acute and chronic ethanol exposure
      can alter gene expression levels in specific neuronal circuits that govern the
      behavioral consequences related to tolerance and dependence. The unremitting
      cycle of alcohol consumption often includes satiation and self-medication with
      alcohol, followed by excruciating withdrawal symptoms and the resultant relapse,
      which reflects both the positive and negative affective states of alcohol
      addiction. Recent studies have indicated that behavioral changes induced by acute
      and chronic ethanol exposure may involve chromatin remodeling resulting from
      covalent histone modifications and DNA methylation in the neuronal circuits
      involving a brain region called the amygdala. These findings have helped identify
      enzymes involved in epigenetic mechanisms, such as the histone deacetylase,
      histone acetyltransferase, and DNA methyltransferase enzymes, as novel
      therapeutic targets for the development of future pharmacotherapies for the
      treatment of alcoholism.

PMID- 23134048
TI  - Bridging Animal and Human Models: Translating From (and to) Animal Genetics.
AB  - Genetics play an important role in the development and course of alcohol abuse,
      and understanding genetic contributions to this disorder may lead to improved
      preventative and therapeutic strategies in the future. Studies both in humans and
      in animal models are necessary to fully understand the neurobiology of alcoholism
      from the molecular to the cognitive level. By dissecting the complex facets of
      alcoholism into discrete, well-defined phenotypes that are measurable in both
      human populations and animal models of the disease, researchers will be better
      able to translate findings across species and integrate the knowledge obtained
      from various disciplines. Some of the key areas of alcoholism research where
      consilience between human and animal studies is possible are alcohol withdrawal
      severity, sensitivity to rewards, impulsivity, and dysregulated alcohol
      consumption.

PMID- 23134049
TI  - Genes contributing to the development of alcoholism: an overview.
AB  - Genetic factors (i.e., variations in specific genes) account for a substantial
      portion of the risk for alcoholism. However, identifying those genes and the
      specific variations involved is challenging. Researchers have used both case
      control and family studies to identify genes related to alcoholism risk. In
      addition, different strategies such as candidate gene analyses and genome-wide
      association studies have been used. The strongest effects have been found for
      specific variants of genes that encode two enzymes involved in alcohol metabolism
      alcohol dehydrogenase and aldehyde dehydrogenase. Accumulating evidence indicates
      that variations in numerous other genes have smaller but measurable effects.

PMID- 23134050
TI  - Genes encoding enzymes involved in ethanol metabolism.
AB  - The effects of beverage alcohol (ethanol) on the body are determined largely by
      the rate at which it and its main breakdown product, acetaldehyde, are
      metabolized after consumption. The main metabolic pathway for ethanol involves
      the enzymes alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Seven
      different ADHs and three different ALDHs that metabolize ethanol have been
      identified. The genes encoding these enzymes exist in different variants (i.e.,
      alleles), many of which differ by a single DNA building block (i.e., single
      nucleotide polymorphisms [SNPs]). Some of these SNPs result in enzymes with
      altered kinetic properties. For example, certain ADH1B and ADH1C variants that
      are commonly found in East Asian populations lead to more rapid ethanol breakdown
      and acetaldehyde accumulation in the body. Because acetaldehyde has harmful
      effects on the body, people carrying these alleles are less likely to drink and
      have a lower risk of alcohol dependence. Likewise, an ALDH2 variant with reduced
      activity results in acetaldehyde buildup and also has a protective effect against
      alcoholism. In addition to affecting drinking behaviors and risk for alcoholism,
      ADH and ALDH alleles impact the risk for esophageal cancer.

PMID- 23134051
TI  - Alcohol Dependence and Genes Encoding alpha2 and gamma1 GABAA Receptor Subunits:
      Insights from Humans and Mice.
AB  - One approach to identifying the causes of alcoholism, particularly without
      crossing ethical boundaries in human subjects, is to look at the person's genome
      (and particularly at the variations that naturally arise in the DNA) to identify
      those variations that seem to be found more commonly in people with the disease.
      Some of these analyses have focused on the genes that encode subunits of the
      receptor for the brain chemical (i.e., neurotransmitter) gamma-aminobutyric acid
      (GABA). Different epidemiological genetic studies have provided evidence that
      variations in certain GABAA receptor (GABAA-R) subunits, particularly subunits
      alpha2 and gamma1, are correlated with alcohol dependence. Manipulations of these
      genes and their expression in mice and rats also are offering clues as to the
      role of specific GABAA-Rs in the molecular mechanisms underlying alcoholism and
      suggest possibilities for new therapeutic approaches.

PMID- 23134052
TI  - Immune function genes, genetics, and the neurobiology of addiction.
AB  - The neuroimmune system (i.e., the immune system and those components of the
      nervous system that help regulate immune responses), and in particular the innate
      immune system, play a role in the development of addictions, including
      alcoholism, particularly in the context of stressful situations. Certain cells of
      the neuroimmune system are activated both by stress and by environmental factors
      such as alcohol, resulting in the induction of genes involved in innate immunity.
      One of the molecules mediating this gene induction is a regulatory protein called
      nuclear factor-kappaB, which activates many innate immune genes. Innate immune
      gene induction in certain brain regions (e.g., the frontal cortex), in turn, can
      disrupt decision making, which is a characteristic of addiction to alcohol and
      other drugs. Likewise, altered neuroimmune signaling processes are linked to
      alcohol-induced negative affect and depression-like behaviors and also regulate
      alcohol-drinking behavior. Moreover, the expression of several genes and proteins
      involved in innate immunity is enhanced in addicted people. Finally, specific
      variants of multiple innate immune genes are associated with the genetic risk for
      alcoholism in humans, further strengthening the connection between increased
      brain innate immune gene expression and alcohol addiction.

PMID- 23134053
TI  - Circadian genes, the stress axis, and alcoholism.
AB  - The body's internal system to control the daily rhythm of the body's functions
      (i.e., the circadian system), the body's stress response, and the body's
      neurobiology are highly interconnected. Thus, the rhythm of the circadian system
      impacts alcohol use patterns; at the same time, alcohol drinking also can alter
      circadian functions. The sensitivity of the circadian system to alcohol may
      result from alcohol's effects on the expression of several of the clock genes
      that regulate circadian function. The stress response system involves the
      hypothalamus and pituitary gland in the brain and the adrenal glands, as well as
      the hormones they secrete, including corticotrophin-releasing hormone,
      adrenocorticotrophic hormone, and glucocorticoids. It is controlled by brain
      signaling molecules, including endogenous opioids such as beta-endorphin. Alcohol
      consumption influences the activity of this system and vice versa. Finally,
      interactions exist between the circadian system, the hypothalamic-pituitary
      adrenal axis, and alcohol consumption. Thus, it seems that certain clock genes
      may control functions of the stress response system and that these interactions
      are affected by alcohol.

PMID- 23134055
TI  - First example of a reversible single-crystal-to-single-crystal polymerization
      depolymerization accompanied by a magnetic anomaly for a transition-metal complex
      with an organic radical.
AB  - The reaction of copper(II) hexafluoroacetylacetonate [Cu(hfac)2] with the stable
      nitronyl nitroxide 2-(1-ethyl-3-methyl-1H-pyrazol-4-yl)-4,4,5,5-tetramethyl-4,5
      dihydro-1H-imidazole-3-oxide-1-oxyl (L(a)) resulted in a paired heterospin
      complex [[Cu(hfac)2]3(MU-O,N-L(a))2][Cu(hfac)2(O-L(a))2]. The crystals of the
      compound were found to be capable of a reversible single-crystal-to-single
      crystal (SC-SC) transformation initiated by the variation of temperature. At room
      temperature, the molecular structure of [[Cu(hfac)2]3(MU-O,N-L(a))2][Cu(hfac)2(O
      L(a))2] is formed by the alternating fragments of the pair complex. Cooling the
      crystals of the complex below 225 K caused considerable mutual displacements of
      adjacent molecules, which ended in a transformation of the molecular structure
      into a polymer chain structure. A reversible topotactic polymerization
      depolymerization coordination reaction actually takes place in the solid during
      repeated cooling-heating cycles: [[Cu(hfac)2]3(MU-O,N-L(a))2][Cu(hfac)2(O-L(a))2]
      ? Cu(hfac)2(MU-O,N-L(a))]infinity. Polymerization during cooling is the result of
      the anomalously great shortening of intermolecular distances (from 4.403 A at 295
      K to 2.460 A at 150 K; Deltad = 1.943 A) between the terminal Cu atoms of the
      trinuclear fragments {[[Cu(hfac)2]3(MU-O,N-L(a))2]} and the noncoordinated N
      atoms of the pyrazole rings of the mononuclear {[Cu(hfac)2(O-L(a))2]} fragments.
      When the low-temperature phase was heated above 270 K, the polymer chain
      structure was destroyed and the compound was again converted to the pair
      molecular complex. The specifics of the given SC-SC transformation lies in the
      fact that the process is accompanied by a magnetic anomaly, because the
      intracrystalline displacements of molecules lead to a considerable change in the
      mutual orientation of the paramagnetic centers, which, in turn, causes modulation
      of the exchange interaction between the odd electrons of the Cu(2+) ion and
      nitroxide. On the temperature curve of chiT, this shows itself as a hysteresis
      loop. The nontrivial character of the recorded spin transition during the cooling
      of the sample below 225 K lies in the fact that the magnetic moment abruptly
      increased. In contrast, heating the sample above 270 K led to a drastic decrease
      in chiT. This behavior of chiT is caused by a stepwise change in the character of
      the exchange interaction in the {>N-(*)O-Cu(2+)-O(*)-N<} fragments. The
      lengthening of distances between the paramagnetic centers on cooling below 225 K
      led to a transition from antiferromagnetic to ferromagnetic exchange and, vice
      versa, the shortening of distances between the paramagnetic centers during the
      heating of the heterospin polymer above 270 K led to a transition from
      ferromagnetic exchange to antiferromagnetic exchange. 

PMID- 23134054
TI  - Discovering genes involved in alcohol dependence and other alcohol responses:
      role of animal models.
AB  - The genetic determinants of alcoholism still are largely unknown, hindering
      effective treatment and prevention. Systematic approaches to gene discovery are
      critical if novel genes and mechanisms involved in alcohol dependence are to be
      identified. Although no animal model can duplicate all aspects of alcoholism in
      humans, robust animal models for specific alcohol-related traits, including
      physiological alcohol dependence and associated withdrawal, have been invaluable
      resources. Using a variety of genetic animal models, the identification of
      regions of chromosomal DNA that contain a gene or genes which affect a complex
      phenotype (i.e., quantitative trait loci [QTLs]) has allowed unbiased searches
      for candidate genes. Several QTLs with large effects on alcohol withdrawal
      severity in mice have been detected, and fine mapping of these QTLs has placed
      them in small intervals on mouse chromosomes 1 and 4 (which correspond to certain
      regions on human chromosomes 1 and 9). Subsequent work led to the identification
      of underlying quantitative trait genes (QTGs) (e.g., Mpdz) and high-quality QTG
      candidates (e.g., Kcnj9 and genes involved in mitochondrial respiration and
      oxidative stress) and their plausible mechanisms of action. Human association
      studies provide supporting evidence that these QTLs and QTGs may be directly
      relevant to alcohol risk factors in clinical populations.

PMID- 23134057
TI  - Mental illness, access to hospitals with invasive cardiac services, and receipt
      of cardiac procedures by Medicare acute myocardial infarction patients.
AB  - OBJECTIVE: Older persons with coronary heart disease have reduced access to
      appropriate medical and surgical services if they are also mentally ill. This
      study determined whether difference exists in access to hospitals that provide on
      site invasive cardiac procedures among a national cohort of Medicare acute
      myocardial infarction (AMI) patients with and without comorbid mental illness,
      and its implications for subsequent procedure use. METHODS: Retrospective
      analyses of Medicare claims for initial AMI admissions between January and
      September 2007. Hospital service availability was obtained from annual survey
      data. Logistic regression estimated the associations of mental illness with
      admission to hospitals with any invasive cardiac services (diagnostic
      catheterization, coronary angioplasty, or bypass surgery) and post-admission care
      patterns and outcomes. RESULTS: Eighty-two percent of mentally ill AMI patients
      (n = 28,888) versus 87 percent of other AMI patients (n = 73,895) were initially
      admitted to hospitals with invasive cardiac facilities [adjusted odds ratio (OR)
      = 0.81, p < .001]. Admission to such hospitals was associated with overall higher
      rate of procedure use within 90 days of admission and improved 30-days
      readmission and mortality rates. However, irrespective of on-site service
      availability of the admitting hospital, mentally ill patients were one half as
      likely to receive invasive procedures (adjusted OR approximately 0.5, p < .001).
      CONCLUSIONS: Among Medicare patients with AMI, those with comorbid mental illness
      were less likely to be admitted to hospitals with on-site invasive cardiac
      services. Mental illness was associated with reduced cardiac procedure use within
      each type of admitting hospitals (with on-site invasive cardiac services or not).

PMID- 23134059
TI  - Hibiscus chlorotic ringspot virus coat protein upregulates sulfur metabolism
      genes for enhanced pathogen defense.
AB  - In both Hibiscus chlorotic ringspot virus (HCRSV)-infected and HCRSV coat protein
      (CP) agroinfiltrated plant leaves, we showed that sulfur metabolism pathway
      related genes-namely, sulfite oxidase (SO), sulfite reductase, and adenosine 5'
      phosphosulfate kinase-were upregulated. It led us to examine a plausible
      relationship between sulfur-enhanced resistance (SED) and HCRSV infection. We
      broadened an established method to include different concentrations of sulfur
      (0S, 1S, 2S, and 3S) to correlate them to symptom development of HCRSV-infected
      plants. We treated plants with glutathione and its inhibitor to verify the SED
      effect. Disease resistance was induced through elevated glutathione contents
      during HCRSV infection. The upregulation of SO was related to suppression of
      symptom development induced by sulfur treatment. In this study, we established
      that HCRSV-CP interacts with SO which, in turn, triggers SED and leads to
      enhanced plant resistance. Thus, we have discovered a new function of SO in the
      SED pathway. This is the first report to demonstrate that the interaction of a
      viral protein and host protein trigger SED in plants. It will be interesting if
      such interaction applies generally to other host-pathogen interactions that will
      lead to enhanced pathogen defense.

PMID- 23134060
TI  - Comparative genomics in the Amoebozoa clade.
AB  - Amoeboid life forms can be found throughout the evolutionary tree. The greatest
      proportion of these life forms is found in the Amoebozoa clade, one of the six
      major eukaryote evolutionary branches. Despite its common origin this clade
      exhibits a wide diversity of lifestyles including free-living and parasitic
      species and species with multicellular and multinucleate life stages. In this
      group, development, cooperation, and social behaviour can be studied in addition
      to traits common to unicellular organisms. To date, only a few Amoebozoa genomes
      have been sequenced completely, however a number of expressed sequence tags
      (ESTs) and complete and draft genomes have become available recently for several
      species that represent some of the major evolutionary lineages in this clade.
      This resource allows us to compare and analyse the evolutionary history and fate
      of branch-specific genes if properly exploited. Despite the large evolutionary
      time scale since the emergence of the major groups the genomic organization in
      Amoebozoa has retained common features. The number of Amoebozoa-specific genetic
      inventions seems to be rather small. The emergence of subgroups is accompanied by
      gene and domain losses and acquisitions of bacterial gene material. The
      sophisticated developmental cycles of Myxogastria and Dictyosteliida likely have
      a common origin and are deeply rooted in amoebozoan evolution. In this review we
      describe initial approaches to comparative genomics in Amoebozoa, summarize
      recent findings, and identify goals for further studies.

PMID- 23134061
TI  - Oryza sativa actin-interacting protein 1 is required for rice growth by promoting
      actin turnover.
AB  - Rapid actin turnover is essential for numerous actin-based processes. However,
      how it is precisely regulated remains poorly understood. Actin-interacting
      protein 1 (AIP1) has been shown to be an important factor by acting coordinately
      with actin-depolymerizing factor (ADF)/cofilin in promoting actin
      depolymerization, the rate-limiting factor in actin turnover. However, the
      molecular mechanism by which AIP1 promotes actin turnover remains largely unknown
      in plants. Here, we provide a demonstration that AIP1 promotes actin turnover,
      which is required for optimal growth of rice plants. Specific down-regulation of
      OsAIP1 increased the level of filamentous actin and reduced actin turnover,
      whereas over-expression of OsAIP1 induced fragmentation and depolymerization of
      actin filaments and enhanced actin turnover. In vitro biochemical
      characterization showed that, although OsAIP1 alone does not affect actin
      dynamics, it enhances ADF-mediated actin depolymerization. It also caps the
      filament barbed end in the presence of ADF, but the capping activity is not
      required for their coordinated action. Real-time visualization of single filament
      dynamics showed that OsAIP1 enhanced ADF-mediated severing and dissociation of
      pointed end subunits. Consistent with this, the filament severing frequency and
      subunit off-rate were enhanced in OsAIP1 over-expressors but decreased in RNAi
      protoplasts. Importantly, OsAIP1 acts coordinately with ADF and profilin to
      induce massive net actin depolymerization, indicating that AIP1 plays a major
      role in the turnover of actin, which is required to optimize F-actin levels in
      plants.

PMID- 23134066
TI  - Apple pie or peach cobbler.

PMID- 23134065
TI  - Cytogenetic studies on newborns from high and normal level natural radiation
      areas of Kerala in southwest coast of India.
AB  - PURPOSE: To study, characterize and compare chromosome aberrations and karyotype
      anomalies among newborns from high (> 1.5 mGy/y) and normal (<= 1.5 mGy/y) level
      natural radiation areas of monazite-sand bearing southwest coast of Kerala in
      India. MATERIALS AND METHODS: Cord blood samples from newborns were collected
      from selected Government hospitals in heparinized vials and cultures were set up
      employing standard microculture techniques, slides were prepared, coded and
      stained with giemsa. Well spread metaphases were analyzed for chromosome
      aberrations and karyotype anomalies. RESULTS: A total of 1,267,788 metaphases
      from 27,295 newborns of mothers aged 17-45 years (17,298 from high and 9,997 from
      normal level radiation areas) were analyzed during 1986-2007. Frequencies of
      dicentrics in high and normal level radiation areas were 1.90 +/- 0.14 and 2.01
      +/- 0.26 per 10,000 cells, respectively (Relative frequency [RF] = 0.94; 95% CI:
      0.71-1.26). Karyotype anomalies had a frequency of 5.490/00 and 6.70/00,
      respectively (RF = 0.82; 95% CI: 0.60-1.12). No dose-related trend was observed
      in chromosome aberrations or karyotype anomalies. CONCLUSION: Frequencies of
      chromosomal aberration and karyotype anomalies between the newborns from the high
      level natural radiation area (HLNRA) and normal level natural radiation areas
      (NLNRA) were very similar.

PMID- 23134067
TI  - Clinical impact of home telemonitoring on patients with chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) affects millions of
      people worldwide. A complication of COPD is exacerbations that result in
      increased utilization of healthcare services, readmissions to the hospital, and a
      decline in health-related quality of life. Home telehealth has been shown both to
      improve health-related quality of life and to reduce admission rates. Using
      clinical data from a home telemonitoring group, this study sought to investigate
      the clinical impact of telemonitoring. SUBJECTS AND METHODS: Fifty-seven subjects
      with COPD were included in a 4-month telemonitoring project. Differences between
      the clinical parameters during the first and last months of participation in the
      project were tested for significance, and the levels for the first month versus
      the difference were tested for correlation. RESULTS: Significant declines were
      observed in prescriptions for antibiotics and steroids (p=0.03), clinical
      consultations (p=0.05), mean systolic blood pressure (p<0.001), standard
      deviation of systolic blood pressure (p=0.03), and mean diastolic blood pressure
      (p=0.02). No significant differences were observed for mean of oxygen saturation
      (p=0.77), standard deviation of oxygen saturation (p=0.36), mean of forced
      expiratory volume in 1 s (p=0.17), mean of forced vital capacity (p=0.29), mean
      of pulse rate (p=0.78), standard deviation of pulse rate (p=0.57), and standard
      deviation of diastolic blood pressure (p=0.27). CONCLUSIONS: The results suggest
      that telemonitoring improves the condition of the patient by lowering the blood
      pressure, the number of prescribed antibiotics and steroids, and the number of
      clinical consultations.

PMID- 23134068
TI  - Max von Pettenkofer award.

PMID- 23134069
TI  - Missing drivers with dementia: antecedents and recovery.
AB  - OBJECTIVES: To determine the circumstances under which persons with dementia
      become lost while driving, how missing drivers are found, and how Silver Alert
      notifications are instrumental in those discoveries. DESIGN: A retrospective,
      descriptive study. SETTING: Retrospective record review. PARTICIPANTS: Conducted
      using 156 records from the Florida Silver Alert program for October 2008 through
      May 2010. These alerts were issued in Florida for missing drivers with dementia.
      MEASUREMENTS: Information derived from the reports on characteristics of the
      missing driver, antecedents to missing event, and discovery of a missing driver.
      RESULTS: The majority of missing drivers were men aged 58 to 94 who were being
      cared for by a spouse. Most drivers became lost on routine, caregiver-sanctioned
      trips to usual locations. Only 15% were driving when found, with most being found
      in or near a parked car. Law enforcement officers found the large majority. Only
      40% were found in the county where they went missing, and 10% were found in a
      different state. CONCLUSION: Silver Alert notifications were most effective for
      law enforcement; citizen alerts resulted in a few discoveries. There was 5%
      mortality in the study population, with those living alone more likely to be
      found dead than alive. An additional 15% were found in dangerous situations such
      as stopped on railroad tracks. Thirty-two percent had documented driving or other
      dangerous errors, such as driving the wrong way or into secluded areas or walking
      in or near roadways.

PMID- 23134071
TI  - Rapid decreases in salinity, but not increases, lead to immune dysregulation in
      Nile tilapia, Oreochromis niloticus (L.).
AB  - Rapid changes in salinity, as with other environmental stressors, can have
      detrimental effects on fish and may trigger increased susceptibility to disease.
      However, the precise mechanisms of these effects are not well understood. We
      examined the effects of sudden increases or decreases in salinity on teleost
      immune function using Nile tilapia, Oreochromis niloticus (L.), as the fish model
      in a battery of bioassays of increasing immune system specificity. Two different
      salinity experiments were performed: one of increasing salinity (0 to 5, 10 and
      20 g L(-1) ) and one of decreasing salinity (20 to 15, 10 and 5 g L(-1) ).
      Histopathology of anterior kidney, gills, gonads, intestines and liver of exposed
      fish was performed, but no remarkable lesions were found that were attributable
      to the salinity treatment regimes. The spleen was removed from each fish for
      analysis of cytokine expression, and peripheral blood was used for haematology,
      cortisol and phagocytosis assays. In the increasing salinity experiments, no
      significant changes were observed in any immune system assays. However, in the
      decreasing salinity experiments, lymphopenia, neutrophilia and monocytosis were
      observed in the peripheral blood without modification of the packed cell volume,
      plasma protein or plasma cortisol levels. Phagocytosis was increased in response
      to decreases in salinity from 20 g L(-1) to 15 g L(-1) , 10 g L(-1) and 5 g L(-1)
      , whereas phagocytic index was not significantly altered. Transforming growth
      factor-beta (TGF-beta) transcription increased during the same decreases in
      salinity. However, the TGF-beta value at 5 g L(-1) was less than those in the 15
      and 10 g L(-1) salinity treatments. Interleukin-1beta (IL-1beta) transcription
      did not significantly respond to either salinity regime. In total, acute salinity
      changes appeared to trigger reactive dysregulation of the immune response in
      tilapia, a situation which, when combined with additional co-occurring stressors
      such as sudden changes in temperature and/or dissolved oxygen, could make fish
      more susceptible to infectious diseases. Accordingly, these findings may help to
      explain how sudden environmental changes may initiate disease outbreaks and lead
      to critical declines in cultured or wild fish populations.

PMID- 23134072
TI  - Direct growth of graphene nanoribbons for large-scale device fabrication.
AB  - Graphene being a zero band gap material hinders the use of its intrinsic form for
      many applications requiring a moderate band gap, such as field effect transistors
      and optoelectronic devices. Here we demonstrate a scalable method based on
      chemical vapor deposition for the direct growth of well-registered graphene
      nanoribbons on SiO(2) substrates with precise control over their width, length,
      and position. The width of the graphene nanoribbons (~20 nm) is defined by the
      thickness of catalyst film, therefore avoiding the diffraction limit of
      conventional optical lithographic methods. The carrier mobility (over 1000
      cm(2)/V.s) is higher than those previously reported graphene nanoribbons
      fabricated on SiO(2) substrates, thanks to the present transfer-free and
      contaminant-free direct growth process. This method overcomes many practical
      limitations of the previously demonstrated methods for the patterning of graphene
      nanoribbons and is compatible with large-scale fabrication of graphene
      nanoelectronics.

PMID- 23134073
TI  - Fibroblast growth factor 21 as an emerging metabolic regulator: clinical
      perspectives.
AB  - Fibroblast growth factor 21 (FGF21), a metabolic hormone predominantly produced
      by the liver, is also expressed in adipocytes and the pancreas. It regulates
      glucose and lipid metabolism through pleiotropic actions in these tissues and the
      brain. In mice, fasting leads to increased PPAR-alpha mediated expression of
      FGF21 in the liver where it stimulates gluconeogenesis, fatty acid oxidation, and
      ketogenesis, as an adaptive response to fasting and starvation. In the fed state,
      FGF21 acts as an autocrine factor in adipocytes, regulating the activity of PPAR
      gamma through a feed-forward loop mechanism. Administration of recombinant FGF21
      has been shown to confer multiple metabolic benefits on insulin sensitivity,
      blood glucose, lipid profile and body weight in obese mice and diabetic monkeys,
      without mitogenic or other side effects. Such findings highlight the potential
      role of FGF21 as a therapeutic agent for obesity-related medical conditions.
      However, in human studies, high circulating FGF21 levels are found in obesity and
      its related cardiometabolic disorders including the metabolic syndrome, type 2
      diabetes, non-alcoholic fatty liver disease and coronary artery disease. These
      findings may indicate the presence of FGF21 resistance or compensatory responses
      to the underlying metabolic stress, and imply the need for supraphysiological
      doses of FGF21 to achieve therapeutic efficacy. On the other hand, serum FGF21
      has been implicated as a potential biomarker for the early detection of these
      cardiometabolic disorders. This review summarizes recent developments in the
      understanding of FGF21, from physiological and clinical perspectives.

PMID- 23134074
TI  - Factors influencing the assessment of lung function in mice with influenza
      induced lung disease.
AB  - BACKGROUND: The constant-phase model (CPM) is commonly fit to respiratory system
      input impedance (Zrs) to estimate lung mechanics. Driving signal frequencies and
      the method of model fitting may influence the results, especially in cases of
      severe lung disease or under severe bronchoconstriction. OBJECTIVE: To illustrate
      the effects of different CPM fits to Zrs data using a mouse model of influenza
      induced lung disease. METHODS: BALB/c mice infected with influenza (or control)
      were challenged with methacholine. The CPM was fitted to Zrs, measured between
      0.25 and 19.625 Hz, using both unweighted and weighted fits. The effect of
      different lowest frequencies was assessed. RESULTS AND CONCLUSIONS: For influenza
      infected mice, the unweighted fit was poor, and airway resistance (Raw) was often
      biologically impossible. The weighted fit provided more realistic estimates of
      Raw. Different model fits and minimal frequencies had little effect on tissue
      mechanics.

PMID- 23134075
TI  - Single-balloon enteroscopy for small bowel diseases: results from an initial
      experience at a single Chinese center.
AB  - OBJECTIVE: This study aimed to evaluate the performance, diagnostic yield, and
      safety of single-balloon enteroscopy (SBE) at a Chinese tertiary-care center.
      METHODS: A total of 67 patients with suspected small bowel diseases who underwent
      SBE via the oral and/or anal routes from January 2009 to August 2011 were
      retrospectively analyzed. Data were extracted from electronic clinical and
      endoscopy records. The indications, SBE procedure time, diagnostic yield and
      complications were summarized and evaluated. RESULTS: A total of 42 SBE
      procedures through the oral route and 38 via the anal route were performed in
      these 67 patients. Patients were referred mainly for obscure gastrointestinal
      bleeding (OGIB) (40.3%) and abdominal pain (29.8%). The mean procedure duration
      was 68.1 min from the oral cavity and 77.5 min from the anus. The estimated depth
      of insertion was 247.6 +/- 80.3 cm from the oral cavity and 131.1 +/- 68.7 cm
      from the anus. The overall significant diagnostic yield was 68.7%. In patients
      with OGIB and unexplained chronic abdominal pain, the diagnostic yield was 74.1%
      and 50.0%, respectively. There were no significant complications. CONCLUSION: SBE
      appears to be a safe and effective method for the diagnosis and treatment of deep
      small bowel disease.

PMID- 23134083
TI  - Non-ketotic hyperglycinaemia: case report and review of medical literature.
AB  - Rare inheritable conditions may present without warning in the neonatal period
      and thus lead curious staff to institute expansive clinical investigations. Non
      ketotic hyperglycaemia (NKH) in a normal fully grown male infant following an
      essentially eventful pregnancy associated with unrelated condition provoked much
      clinical curiosity. NKH should therefore be included as a differential diagnosis
      in an unwell neonate presenting with hiccoughs, seizures, myotonic jerks, and
      hypotonia as our very unique case clearly demonstrated.

PMID- 23134084
TI  - Evaluation of toxicity and single-dose pharmacokinetics of intravenous ursolic
      acid liposomes in healthy adult volunteers and patients with advanced solid
      tumors.
AB  - OBJECTIVE: The purpose of this study was to investigate the maximum tolerated
      dose (MTD), dose-limiting toxicity (DLT), and pharmacokinetics of ursolic acid
      liposomes (UAL), as a new drug, in healthy adult volunteers and patients with
      advanced solid tumors. METHODS: All subjects received a single-dose of UAL (11,
      22, 37, 56, 74, 98, and 130 mg/m(2)) administered as a 4-h intravenous infusion.
      Toxicity was assessed and plasma samples were analyzed using validated ultra
      performance liquid chromatograph/tandem mass spectroscopy method. RESULTS: A
      total of 63 subjects including 4 patients and 35 healthy adult volunteers for
      toxicity study and 24 healthy adult volunteers for pharmacokinetic study were
      enrolled in this trial. The DLT was encountered at 74, 98, and 130 mg/m(2), and
      consisted of hepatotoxicity and diarrhea. Other adverse events included grade 1
      nausea, grade 2 abdominal distention, grade 1 microscopic hematuria, grade 2
      elevated serum sodium, grade 1 vascular stimulation, and grade 1 skin rash. The
      MTD was 98 mg/m(2). The single-dose pharmacokinetic parameters revealed a linear
      relationship between C(max), AUC(0->24 h), or AUC(0->infinity) and escalated
      doses. CONCLUSIONS: The clinical data reported for the first time that UAL had
      manageable toxicities with MTD of 98 mg/m(2). The DLT were hepatotoxicity and
      diarrhea. Meanwhile, UAL had a linear pharmacokinetic profile. The registration
      number of this trial is ChiCTR-ONC-12002385.

PMID- 23134085
TI  - Responding to the World Report on Disability in Australia: lessons from
      collaboration in an urban Aboriginal and Torres Strait Islander school.
AB  - The timely release of the World Report on Disability serves as a challenge to
      members of the health professions to review and renew their response to inequity
      of access and provision of services to children and adults with a disability.
      This paper responds to the lead article by Wylie, McAllister, Davidson, and
      Marshall, and provides commentary on two of the recommendations of the World
      Report on Disability in the context of a novel inter-professional service for
      Aboriginal and Torres Strait Islander children with communication and learning
      needs. Speech-language pathology and occupational therapy students reported on
      their learning within a model of service delivery based on partnership with an
      Aboriginal and Torres Strait Islander school community and inter-professional
      collaboration. Lessons learned have the potential to inform future services for
      under-served populations and to impact on capacity building through health
      professionals gaining experiential knowledge and understanding of an urban
      Aboriginal and Torres Strait Islander community.

PMID- 23134086
TI  - Rapid simultaneous identification and determination of the multiple compounds in
      crude Fructus Corni and its processed products by HPLC-MS/MS with multiple
      reaction monitoring mode.
AB  - CONTEXT: Fructus Corni, a traditional Chinese medicines, is derived from the dry
      ripe sarcocarp of Cornus officinalis Sieb. et Zucc (Cornaceae). Gallic acid, 5
      hydroxymethylfurfural, morroniside, sweroside, loganin, cornin, 7-O-methyl
      morroniside and cornuside are the active constituents of Fructus Corni used in
      many traditional Chinese medicines. This paper describes a sensitive and specific
      assay for the determination of the eight bioactive compounds in crude and
      processed Fructus Corni extracts. MATERIALS AND METHODS: In this paper, the eight
      components were determined by high performance liquid chromatography coupled with
      triple quadrupole mass spectrometry (MS/MS). Quantization was based on multiple
      reaction monitoring using the precursor production combination for determination
      of the eight analytes. The analysis was performed on an Agilent Zorbax Extend
      C(18) column (100 mm * 3.0 mm, 3.5 MUm), and an electrospray ionization (ESI)
      tandem interface in the positive and negative ion polarity mode was employed
      prior to mass spectrometric detection. RESULTS: With the optimized conditions,
      the eight bioactive compounds were detected properly within 10 min. The developed
      method showed good precision and reproducibility with the limits of detection
      ranged from 0.0042 to 12.7875 ng/mL and the average recoveries ranged from 97.08
      to 103.7%. DISCUSSION AND CONCLUSION: This newly established method is validated
      as simple, reliable and accurate. It can be used as a valid analytical method for
      intrinsic quality control of crude and processed Fructus Corni.

PMID- 23134087
TI  - Ionizing radiation causes active degradation and reduces matrix synthesis in
      articular cartilage.
AB  - PURPOSE: Little is known regarding radiation effects on adult articular (joint)
      cartilage, though joint damage has been reported following cancer treatment or
      occupational exposures. The aim of this study was to determine if radiation can
      reduce cartilage matrix production, induce cartilage degradation, or interfere
      with the anabolic effects of IGF-1. MATERIALS AND METHODS: Isolated chondrocytes
      cultured in monolayers and whole explants harvested from ankles of human donors
      and knees of pigs were irradiated with 2 or 10 Gy gamma-rays, with or without IGF
      1 stimulation. Proteoglycan synthesis and IGF-1 signaling were examined at Day 1;
      cartilage degradation throughout the first 96 hours. RESULTS: Human and pig
      cartilage responded similarly to radiation. Cell viability was unchanged. Basal
      and IGF-1 stimulated proteoglycan synthesis was reduced following exposure,
      particularly following 10 Gy. Both doses decreased IGF-induced Akt activation and
      IGF-1 receptor phosphorylation. Matrix metalloproteinases (ADAMTS5, MMP-1, and
      MMP-13) and proteoglycans were released into media after 2 and 10 Gy.
      CONCLUSIONS: Radiation induced an active degradation of cartilage, reduced
      proteoglycan synthesis, and impaired IGF-1 signaling in human and pig
      chondrocytes. Lowered Akt activation could account for decreased matrix
      synthesis. Radiation may cause a functional decline of cartilage health in joints
      after exposure, contributing to arthropathy.

PMID- 23134088
TI  - Clinical and subclinical infections with Cryptosporidium in animals.
AB  - Cryptosporidium spp. are frequent parasites of livestock and companion animals,
      raising questions about the clinical significance of such infections.
      Cryptosporidium infections have a wide spectrum of clinical signs that can vary
      from asymptomatic to serious infection to death. In neonatal ruminants,
      cryptosporidiosis is considered an important disease characterised by diarrhoea
      and mortality. In companion animals most infections are asymptomatic but severe
      clinical illness has also been reported in dogs, cats and horses. In birds, three
      main clinical forms of cryptosporidiosis are primarily seen in naturally
      occurring infections, i.e. respiratory, intestinal, and renal. In reptiles,
      cryptosporidiosis is an emerging problem given that infections are frequently
      chronic and lethal. Molecular tools have been developed to detect and
      differentiate Cryptosporidium at the species/genotype and subtype levels. The use
      of those tools has led to a more in-depth understanding of the genetic diversity
      of Cryptosporidium which plays an important role in the diverse clinical
      presentations of cryptosporidiosis. This review presents an overview of the
      current knowledge on clinical cryptosporidiosis in livestock, pets, and other
      animals.

PMID- 23134089
TI  - Thermally induced parametric instability in a back-action evading measurement of
      a micromechanical quadrature near the zero-point level.
AB  - We report the results of back-action evading experiments utilizing a tightly
      coupled electro-mechanical system formed by a radio frequency micromechanical
      resonator parametrically coupled to a NbTiN superconducting microwave resonator.
      Due to excess dissipation in the microwave resonator, we observe a parametric
      instability induced by a thermal shift of the mechanical resonance frequency. In
      light of these measurements, we discuss the constraints on microwave dissipation
      needed to perform BAE measurements far below the zero-point level.

PMID- 23134090
TI  - Astrobiology outreach and the nature of science: the role of creativity.
AB  - There is concern in many developed countries that school students are turning
      away from science. However, students may be choosing not to study science and
      dismissing the possibility of a scientific career because, in the junior
      secondary years, they gain a false view of science and the work of scientists.
      There is a disparity between science as it is portrayed at school and science as
      it is practiced. This paper describes a study to explore whether engaging in
      science through astrobiology outreach activities may improve students'
      understanding of the nature and processes of science, and how this may influence
      their interest in a career in science. The results suggest that the students
      attending these Mars research-related outreach activities are more interested in
      science than the average student but are lacking in understanding of aspects of
      the nature of science. A significant difference was detected between pre- and
      posttest understandings of some concepts of the nature of science.

PMID- 23134091
TI  - Do early career indicators of clinical skill predict subsequent career outcomes
      and practice characteristics for general internists?
AB  - OBJECTIVE: To study relationships between clinical skill measures assessed at the
      beginning of general internists' careers and their career outcomes and practice
      characteristics. DATA SOURCES: General Internist Community Tracking Study
      Physician Survey respondents (2000-2001, 2004-2005) linked with residency program
      evaluations and American Board of Internal Medicine board certification
      examination score records; n = 2,331. STUDY DESIGN: Cross-sectional regressions
      of career outcome and practice characteristic measures on board examination
      scores/success, residency evaluations interacted with residency type, and
      potential confounding variables. PRINCIPAL FINDINGS: Failure to achieve board
      certification was associated with $27,206 (18 percent, p < .05) less income and
      14.9 percent more minority patients relative to physicians scoring in the bottom
      quartile on their initial examination who eventually became certified (p < .01).
      Other skill measures were not associated with income. Scoring in the top rather
      than bottom quartile on the board certification examination was associated with 9
      percent increased likelihood of reporting high career satisfaction (p < .05).
      Among physicians trained in community hospital residency programs, lower
      evaluations were associated with 14.5 percent higher share of minority patients
      (p < .05). Both skill measures were associated with practice type. CONCLUSIONS:
      There are associations between early career skill measures and career outcomes.
      In addition, minority patients are more likely to be treated by physicians with
      lower early career clinical skills measures than nonminority patients.

PMID- 23134092
TI  - Good management is critical to professional development and employee well-being.

PMID- 23134093
TI  - Quality Use of Medicines--medication safety issues in naming; look-alike, sound
      alike medicine names.
AB  - OBJECTIVE: To review current literature with the objective of developing
      strategies and recommendations to enhance patient safety and minimise clinical
      issues with look-alike, sound-alike medication names. METHODS: A comprehensive
      search of the PubMed database and an Australian online repository of Quality Use
      of Medicines projects was conducted to identify publications addressing look
      alike, sound-alike medication problems. Author networks, grey literature and the
      reference lists of published articles were also used to identify additional
      material. KEY FINDINGS: Thirty-two publications describing the extent of the
      specific problem and recommending solutions were identified. The majority of
      these publications provided a qualitative assessment of the issues, with few
      quantitative estimates of the severity of the problem and very little
      intervention research. As a result, most recommendations for addressing the
      problem are the result of expert deliberations and not experimental research.
      This will affect the capacity of the recommendations to ameliorate and resolve
      problems caused by look-alike, sound-alike medication names. Themes identified
      from articles included the nature and causes of look-alike, sound-alike problems,
      potential solutions and recommendations. CONCLUSIONS: There are many existing
      medications which can potentially cause clinical issues due to mix-ups because of
      similar sounding or looking medication names. This confusion can be lethal for
      some medication errors. A multifaceted, integrated approach involving all aspects
      of the medication use process, from initial naming of INN through to consumer
      education, is suggested to minimise this issue for medication safety.

PMID- 23134094
TI  - The influence of evidence-based medicine training on decision-making in relation
      to over-the-counter medicines: a qualitative study.
AB  - OBJECTIVES: To explore the role of evidence of effectiveness when making
      decisions about over-the-counter (OTC) medication and to ascertain whether
      evidence-based medicine training raised awareness in decision-making.
      Additionally, this work aimed to complement the findings of a previous study
      because all participants in this current study had received training in evidence
      based medicine (unlike the previous participants). METHODS: Following ethical
      approval and an e-mailed invitation, face-to-face, semi-structured interviews
      were conducted with newly registered pharmacists (who had received training in
      evidence-based medicine as part of their MPharm degree) to discuss the role of
      evidence of effectiveness with OTC medicines. Interviews were recorded and
      transcribed verbatim. Following transcription, all data were entered into the
      NVivo software package (version 8). Data were coded and analysed using a constant
      comparison approach. KEY FINDINGS: Twenty-five pharmacists (7 males and 18
      females; registered for less than 4 months) were recruited and all participated
      in the study. Their primary focus with OTC medicines was safety; sales of
      products (including those that lack evidence of effectiveness) were justified
      provided they did no harm. Meeting patient expectation was also an important
      consideration and often superseded evidence. Despite knowledge of the concept,
      and an awareness of ethical requirements, an evidence-based approach was not
      routinely implemented by these pharmacists. Pharmacists did not routinely utilize
      evidence-based resources when making decisions about OTC medicines and some felt
      uncomfortable discussing the evidence-base for OTC products with patients.
      CONCLUSIONS: The evidence-based medicine training that these pharmacists received
      appeared to have limited influence on OTC decision-making. More work could be
      conducted to ensure that an evidence-based approach is routinely implemented in
      practice.

PMID- 23134095
TI  - Public knowledge and awareness of cardiovascular disease and its risk factors: a
      cross-sectional study of 1000 Jordanians.
AB  - OBJECTIVE: To assess the level of the current knowledge and understanding of
      cardiovascular disease (CVD) among Jordan's general public, their behaviour
      towards CVD and the factors associated with different CVD knowledge levels.
      METHODS: The data in the present study were collected using an interview
      administered questionnaire. One thousand members of the general public were
      interviewed face to face. CVD knowledge was computed as a continuous variable.
      KEY FINDINGS: The present study reports limited public knowledge and awareness of
      CVD. Participants were more likely to have better CVD knowledge scores if they
      were non-smokers, always or often paid attention to their diet, reported having
      an 'about right' weight, occupied a very high socioeconomic level, held a
      university degree and had positive family history of CVD. Participants indicated
      that the community pharmacists had to play a role in helping patients manage
      their prescribed medicines; however, they did not recognise the community
      pharmacists' role in other areas of CVD prevention and management. CONCLUSION:
      The present study reports that the general public in Jordan has limited knowledge
      and awareness of CVD. In planning to positively impact CVD prevention and
      management, community pharmacists must develop and promote effective and
      accessible services.

PMID- 23134096
TI  - Pharmacists' experiences and attitudes regarding generic drugs and generic
      substitution: two sides of the coin.
AB  - OBJECTIVE: Generic drug substitution reduces costs for medicines, but the
      downsides include unintentional double medication, confusion and anxiety among
      patients. Information from pharmacists affects patients' experiences of
      substitution with generic drugs. The aim of this study was to explore experiences
      and attitudes to generic substitution among Swedish community pharmacists.
      METHODS: An interview guide was developed. Semi-structured interviews with
      community pharmacists were conducted and transcribed verbatim. Analysis was
      inductive; extracts from the transcripts were compared and combined to form
      themes and subcategories. Pharmacists from a heterogeneous convenience sample of
      pharmacies were interviewed until data saturation had been achieved. KEY
      FINDINGS: Sixteen pharmacists were interviewed. Three main themes and twelve
      subcategories were identified, with the main themes being the role of the
      pharmacist, pharmacists' concerns regarding patients, and the generic drug.
      Pharmacists found it positive that generic substitution decreases the costs for
      pharmaceuticals but also emphasized that the switch can confuse and worry
      patients, which could result in less benefit from treatment. Respondents claimed
      that generic substitution has changed the focus in the pharmacist-patient meeting
      towards economics and regulations. CONCLUSION: According to the interviewed
      pharmacists generic substitution is not primarily an issue of generic versus
      brand-name products, but concerns above all the challenges that the switch
      implies for patients and pharmacists. To prevent known confusion and concerns
      among patients it is important that community pharmacists acquire the necessary
      tools and knowledge to manage this situation; pharmacists themselves as well as
      pharmacy owners and authorities share responsibility for this.

PMID- 23134097
TI  - The benefits of pharmacist-delivered warfarin education in the home.
AB  - OBJECTIVES: Good warfarin knowledge is important for optimal patient outcomes,
      but barriers exist to effective education and warfarin knowledge is often poor.
      This study aimed to explore the educational outcomes of home-based warfarin
      education provided by trained pharmacists. METHODS: In a prospective, non
      randomised, controlled cohort trial, patients received either usual community
      based post-discharge care or a post-discharge warfarin management service,
      including warfarin education by trained pharmacists during two or three home
      visits. Patients' warfarin knowledge was assessed at 8 and 90 days post-discharge
      using the Oral Anticoagulation Knowledge test. KEY FINDINGS: One hundred and
      thirty-nine patients were recruited into the usual care group between November
      2008 and August 2009, and 129 into the intervention group between May and
      December 2009. Pharmacist-delivered warfarin education was associated with a
      significant difference between the intervention patients' baseline and day 8 mean
      warfarin knowledge scores of 64.5% (95% confidence interval (CI) 61.0-68.5%) and
      78.0% (95% CI 74.5-81.5%; P < 0.001), respectively. The intervention patients
      also scored significantly higher than the usual care patients at day 8 (65.0%,
      95% CI 61.5-68.0%; P < 0.001), but not at day 90. CONCLUSIONS: Use of an existing
      healthcare framework overcame several systemic barriers by facilitating warfarin
      education in patients' homes. While the intervention was associated with better
      short-term warfarin knowledge, follow-up may be required to optimise its
      benefits. Widespread implementation of home-based warfarin education by
      pharmacists has the potential to contribute significantly to improved outcomes
      from warfarin therapy.

PMID- 23134098
TI  - Access to antiepileptic drug therapy in children in Camaguey Province, Cuba.
AB  - OBJECTIVE: To describe access to antiepileptic drug therapy and estimate the
      prevalence of epilepsy in children in Camaguey Province, Cuba. METHODS: All the
      community pharmacies in the province were visited and information collected about
      the number of children receiving antiepileptic drugs in 2009. Availability and
      cost of each antiepileptic drug were determined. The prevalence of epilepsy was
      estimated by determining the number of children receiving antiepileptic drugs.
      RESULTS: There were 923 children who received a total of 977 antiepileptic drugs
      in Camaguey Province. The estimated prevalence of epilepsy was 5.18 per thousand
      children which is lower than previously reported rates in other low and lower
      middle income countries. Most of the children (871, 94%) received a single
      antiepileptic drug. Carbamazepine and valproate were the two most frequently
      prescribed antiepileptic drugs. Antiepileptic drugs were available from the local
      pharmacy on 76% of occasions. If the antiepileptic drug was not available from
      the local pharmacy, the parent had to travel to another pharmacy to obtain the
      medicine. CONCLUSIONS: The estimated prevalence of epilepsy in children in Cuba
      is lower than that estimated in other lower-middle income countries. Access to
      drug therapy in children with epilepsy can be achieved in lower-middle income
      countries.

PMID- 23134099
TI  - Does a primary care practice pharmacist improve the timeliness and completion of
      medication management reviews?
AB  - OBJECTIVE: To describe the effect of integrating a pharmacist into the general
      practice team on the timeliness and completion of pharmacist-conducted medication
      reviews. METHOD: A pharmacist was integrated into an Australian inner-city suburb
      general practice medical centre to provide medication reviews for practice
      patients. A retrospective analysis of medication reviews with two time periods
      was conducted: pre-integration of the practice pharmacist and post-integration of
      the practice pharmacist. In an effort to obtain a measure of external validity
      the data were compared to data from the Division of General Practice in which the
      medical centre is located. KEY FINDINGS: There were 70 patients referred for
      medication review in the pre-integration phase and 314 patients referred in the
      post-integration phase. The time to complete the medication review process was
      significantly reduced from a median of 56 days to 20 days with a practice
      pharmacist. Prior to having a practice pharmacist 52% of patients did not have
      the service billed by the general practitioner, which was reduced to 6% during
      the post-integration phase. CONCLUSION: The results from this trial show that the
      integration of a pharmacist into the general practice team was associated with an
      increase in the timeliness and completion rate of medication reviews.

PMID- 23134100
TI  - Drug-drug interactions in the medical intensive care unit: an assessment of
      frequency, severity and the medications involved.
AB  - OBJECTIVES: Mortality and morbidity are increased in patients experiencing drug
      drug interactions (DDIs). Critically ill patients are at an increased risk of
      adverse events from DDIs due to the large number of medications that they take
      and their changes in organ function. Currently, there is a lack of literature
      describing DDIs in the intensive care unit (ICU). The purpose of this study is to
      evaluate frequency, severity and drug combinations involved in DDIs occurring in
      a medical ICU (MICU). METHODS: This was a 4-week, prospective, observational
      study that was conducted in the MICU of an academic medical centre. Lexi-Interact
      and Micromedex interaction databases were utilized daily to screen patients'
      medication profiles for DDIs, and severity was assessed using each database's
      severity rating scale. KEY FINDINGS: Of 240 patient medication profiles
      evaluated, 457 DDIs were identified. The rate of DDIs was 190.4 DDIs/100 patient
      days with 297 of these interactions being unique drug pairs. About 25% (114/457)
      were considered major DDIs. The most commonly involved medications were
      antihypertensive medications (106/457) and anticoagulants/antiplatelet agents
      (80/457). CONCLUSIONS: DDIs occur frequently in the MICU. Severity and drug
      combinations related to DDIs in the MICU differ from DDIs published in other ICU
      settings. When developing a DDI alerting system, patient characteristics and
      location should be considered.

PMID- 23134101
TI  - Impact of a debate on pharmacy students' views of online pharmacy practice.
AB  - OBJECTIVES: To evaluate the impact of a debate on pharmacy students' perceptions,
      using online pharmacy practice as the debate topic. METHODS: This is a quasi
      experimental interrupted time-series study. A 60 min debate was organized as a
      lunchtime meeting. A four-category Likert scale questionnaire (fully agree,
      partially agree, partially disagree, fully disagree) measured the debate
      participants' level of agreement with 25 statements (main issues associated with
      online pharmacy) in the pre-phase (before the debate), post-phase 1 (after the
      debate) and post-phase 2 (6 months after the debate). One hundred and seventy
      seven students were recruited (response rate of 100% in the pre-phase and post
      phase 1, 31% in post-phase 2). Four questions measured the perceptions of the
      students on this pedagogical technique. KEY FINDINGS: The overall proportion of
      respondents in favour of online pharmacy practice showed little variation among
      the three phases. However, on average (mean +/- SD) 43 +/- 8% of the respondents
      changed their opinion, 21 +/- 7% reversed their opinion, 22 +/- 4% nuanced their
      opinion and 1 +/- 1% radically changed their opinion. Respectively 98% (post
      phase 1) and 96% (post-phase 2) of the respondents were of the opinion that
      debate was a very useful teaching formula in their pharmacist training and 79 and
      66% thought debate significantly changed their opinion of the issue. CONCLUSIONS:
      Few data have been collected on the use of debates as part of healthcare
      professional training. The impact of a debate on how pharmacy students feel about
      online pharmacy practice is described.

PMID- 23134102
TI  - An assessment of community pharmacists' responses to hypothetical medical
      emergency situations.
AB  - OBJECTIVE: To investigate community pharmacists' proposed actions in hypothetical
      medical emergency situations in South-East Queensland, Australia. METHOD: A
      survey was posted to 151 Gold Coast and Toowoomba community pharmacies in October
      2009. Pharmacists were asked to document their opinions regarding the
      pharmacist's role in medical emergencies and to respond to statements associated
      with two hypothetical medical emergency situations: an anaphylaxis and an asthma
      attack. KEY FINDINGS: Forty-five pharmacists responded to the survey (29.8%). In
      response to a hypothetical situation involving an asthma attack, 41 pharmacists
      (91.1%) agreed that they would assist the asthmatic person to administer
      salbutamol through a spacer, with 28 pharmacists (62.2%) confident in treating an
      asthma attack in the pharmacy. In comparison, only 21 pharmacists (21/38; 55.3%)
      agreed to administer an adrenaline auto-injector (Epi-Pen) for a child
      experiencing an anaphylaxis, with nine respondents (9/38; 23.7%) indicating that
      they would ask the mother for directions in a situation where they were unsure
      how to administer it. There were comments questioning whether indemnity insurance
      covers pharmacists for medicine administration, and 12 pharmacists (12/38; 31.6%)
      indicated that if they were unsure about insurance cover they would ask the
      mother to administer the adrenaline. CONCLUSION: Pharmacists' responses to
      administering medications in hypothetical medical emergencies were variable. The
      cause of this variation is multi-factorial and likely to include familiarity with
      the medication, its safety profile and uncertainty about the pharmacist's role
      and responsibilities in these situations. Further clarification, training and
      guidelines are needed in order to address this.

PMID- 23134103
TI  - Are all pharmacy staff interested in potential future roles?
AB  - OBJECTIVES: To determine the current perceived roles and responsibilities of
      pharmacy staff in community pharmacies in New Zealand, and attitudes to proposed
      new advanced roles for pharmacy staff. METHODS: Structured interviews were
      conducted within five community pharmacies, including at least two pharmacists,
      two dispensary staff and two pharmacy assistants. The interviews were structured
      to determine previous experience, current roles and responsibilities and the
      perceived future roles of pharmacy staff within a community pharmacy setting.
      Thematic analysis from 27 interviews identified key findings. KEY FINDINGS:
      Current roles appeared to be fairly well defined. Pharmacy assistants listed key
      roles as customer interactions and sales focus, noting that the dispensary was
      outside their area of responsibility. Technicians identified their role as being
      dispensary focused while pharmacists saw their role as the 'final check' to
      ensure accuracy as well as providing dispensing, counselling and managerial
      roles. With potential future roles, the assistants were less interested than the
      other groups, citing contentment with current situation and training as a
      barrier. Some technicians indicated an interest in furthering their roles, but
      many were reluctant and saw that additional training was too time consuming.
      Whilst pharmacists appeared to be interested in further scopes of practice, they
      appeared more reluctant to do this at the expense of handing dispensing
      responsibility to a non-pharmacist. CONCLUSIONS: Whilst there is a push for
      pharmacists to provide advanced clinical services, it is important to acknowledge
      that many staff working within community pharmacies are satisfied with their
      current role.

PMID- 23134104
TI  - Efficacy of florfenicol for control of mortality associated with Francisella
      noatunensis subsp. orientalis in Nile tilapia, Oreochromis niloticus (L.).
AB  - Francisella noatunensis subsp. orientalis (Fno) (syn. F. asiatica) is an emergent
      Gram-negative facultative intracellular bacterium. Although it is considered one
      of the most pathogenic bacteria in fish, there are no commercially available
      treatments or vaccines. The objective of this project was to determine the most
      efficacious concentration of florfenicol (FFC) [10, 15 or 20 mg FFC kg(-1) body
      weight (bw) per days for 10 days] administered in feed to control experimentally
      induced infections of Fno in Nile tilapia, Oreochromis niloticus (L.), reared in
      a recirculating aquaculture system. The cumulative mortality of fish that
      received 0, 10, 15 or 20 mg FFC kg(-1)  bw per day was 60, 37, 14 and 16%,
      respectively. Francisella noatunensis subsp. orientalis genome equivalents were
      detected in water from all challenged groups with slight reduction in the
      concentration in the florfenicol-treated groups 4 days after treatment. The mean
      LOG of CFU Fno mg(-1) spleen was 3-5 and was present in all challenged groups at
      necropsy 11 days after treatment (21 days after challenge). Results show that
      florfenicol administered at doses of 15 and 20 mg FFC kg(-1)  bw per days for 10
      days significantly reduced mortality associated with francisellosis in Nile
      tilapia.

PMID- 23134105
TI  - Statements of the Malaysian Society of Gastroenterology & Hepatology and the
      National Heart Association of Malaysia task force 2012 working party on the use
      of antiplatelet therapy and proton pump inhibitors in the prevention of
      gastrointestinal bleeding.
AB  - The working party statements aim to provide evidence and guidelines to practising
      doctors on the use of antiplatelet therapy and proton pump inhibitors (PPIs) in
      patients with cardiovascular risk as well as those at risk of gastrointestinal
      (GI) bleeding. Balancing the GI and cardiovascular risk and benefits of
      antiplatelet therapy and PPIs may sometimes pose a significant challenge to
      doctors. Concomitant use of anti-secretory medications has been shown to reduce
      the risk of GI bleeding but concerns have been raised on the potential
      interaction of PPIs and clopidogrel. Many new data have emerged on this topic but
      some can be confusing and at times controversial. These statements examined the
      supporting evidence in four main areas: rationale for antiplatelet therapy, risk
      factors of GI bleeding, PPI-clopidogrel interactions and timing for recommencing
      antiplatelet therapy after GI bleeding, and made appropriate recommendations.

PMID- 23134106
TI  - Antihyperglycemic, antilipid peroxidation, and insulin secretory activities of
      Otostegia persica shoot extract in streptozotocin-induced diabetic rats and in
      vitro C187 pancreatic beta-cells.
AB  - CONTEXT: Otostegia persica Boiss (Lamiaceae) contains antioxidant agents and is
      used in traditional medicine for treatment of diabetes mellitus complications.
      OBJECTIVES: The acute antihyperglycemic, antilipid peroxidation, and insulin
      secretory activities of methanol extract of O. persica aerial parts were
      investigated. MATERIALS AND METHODS: The extract [200, 300, 400 mg/kg body weight
      (b.w.)] was given orally to rats and glucose (2 g/kg b.w. orally) was
      administered 30 min later. Glucose and insulin serum levels were measured before
      and 30, 60, 120, and 240 min after administration of the test samples in normal
      and diabetic rats. The in vitro insulin secretory activity of extract was
      evaluated in C187 pancreatic beta-cells and its antilipid peroxidation effect was
      determined by measuring malondialdehyde (MDA) and glutathione (GSH) levels in rat
      livers after 240 min. The identification of the major phytoconstituents of the
      extract was carried out using gas chromatography-mass spectrometry. RESULTS: The
      extract (300 mg/kg b.w.) significantly decreased the serum glucose level in
      diabetic rats at 1 h (494 +/- 13.4 vs. 426 +/- 12.9), 2 h (472.8 +/- 17.8 vs. 396
      +/- 22), and 4 h (438.8 +/- 25 vs. 346 +/- 19) after treatment. Accordingly, the
      serum insulin level increased at the same times. The extract significantly
      increased glucose-induced insulin secretion in C187 beta-cells. Moreover, the
      extract significantly decreased MDA and increased GSH levels in the liver of
      diabetic rats. Phytochemical analysis revealed thymol as the major
      phytoconstituent in the extract. DISCUSSION AND CONCLUSION: O. persica shoot
      extract has antihyperglycemic, antilipid peroxidation, and insulin secretory
      properties.

PMID- 23134109
TI  - Ultrasonographic assessment of the spleen in 60 healthy sheep.
AB  - AIM: To evaluate the sonographic appearance, size, location and shape of the
      spleen in 60 healthy sheep. METHODS: A 7.5 MHz linear scanner was used to examine
      the location, extent and appearance of the spleen from the left side of the
      sheep, in intercostal spaces (ICS) 8-12 and caudal of the last rib. RESULTS: The
      ultrasonographic appearance of the splenic parenchyma was homogeneous with a
      thin, smooth echogenic capsule. The spleen could be visualized in intercostal
      spaces 9-12 in all sheep, in intercostal space 8 in 25/60 sheep (42%) and caudal
      of the last rib in 24/60 sheep (40%). In intercostal spaces 8-12 and caudal of
      the last rib the spleen was visible in 16/60 sheep (27 %). The distance from the
      dorsal margin of the spleen to the spinous processes of the thoracic vertebrae
      was greatest in the 8th intercostal space: mean 19.32 (SD 2.76) cm and smallest
      in the 12th intercostal space: mean 6.61 (SD 1.94) cm. The dorsoventral splenic
      extent was greatest in the 11th intercostal space: mean 13.69 (SD 2.2) cm and
      smallest in the 8th intercostal space: mean 7.13 (SD 2.5) cm. The thickness of
      the spleen ranged from 21 (SD 9.0) mm in the 8th intercostal space to 49 (SD 7.0)
      mm in the 11th intercostal space. The mean vessel diameter was 1.9 (SD 0.7) mm.
      Spleen size did not correlate with age, body weight, or thoracic and abdominal
      circumference. CONCLUSIONS: Ultrasonography is a useful, straightforward and non
      invasive method for evaluation of the spleen in sheep. CLINICAL RELEVANCE: These
      findings provide information which can be used as a reference for sonographic
      spleen examination and diagnosis of splenic lesions in sheep.

PMID- 23134110
TI  - BclI polymorphism of the glucocorticoid receptor gene is associated with
      increased bone resorption in patients on glucocorticoid replacement therapy.
AB  - CONTEXT: Patients with primary adrenal insufficiency (PAI) and patients with
      congenital adrenal hyperplasia (CAH) receive weight-adapted standard
      glucocorticoid replacement therapy. Clinically, some patients appear more
      sensitive to therapeutic administration of glucocorticoids than others.
      Glucocorticoid sensitivity is at least partially genetically determined by
      polymorphisms of the glucocorticoid receptor (GR) and might influence bone
      mineral density (BMD). OBJECTIVES: To determine if bone turnover markers and BMD
      are associated with the GR gene polymorphism BclI in patients with PAI and CAH.
      DESIGN AND PATIENTS: A prospective, cross-sectional study including 74 PAI and 38
      CAH patients. BMD was evaluated by DXA. Serum levels of bone turnover markers,
      minerals, vitamins and hormones, and urinary crosslinks were measured. RESULTS:
      Patients carrying the homozygous BclI polymorphism (GG) had significantly higher
      serum beta-CrossLaps (0.37 +/- 0.34 MUg/l; P < 0.05) and urinary collagen
      crosslinks (NTX, 68.1 +/- 32.4 nmol/g; P < 0.005) despite receiving the lowest
      average daily hydrocortisone dose of 9.9 +/- 3.7 mg/m(2) (P < 0.05). The GG
      genotype occurred significantly more frequently in patients with increased NTX
      (OR=6.7, 95% CI = 1.78-25.38) than in patients with normal NTX. However, BMD was
      not significantly different between different allelic variants. No significant
      differences in associations of the genotypes with outcomes (or in clinical
      characteristics) were found between the sexes. CONCLUSIONS: Although the sample
      sizes were relatively small and the results should be interpreted with caution,
      this study suggests that the homozygous (GG) genotype may be associated with
      higher bone resorption in adult PAI and CAH patients. GG-carriers needed a lower
      hydrocortisone dose on average supporting the concept that this GR variant is
      associated with increased cortisol sensitivity.

PMID- 23134111
TI  - Targeted gene transfer of hepatocyte growth factor to alveolar type II epithelial
      cells reduces lung fibrosis in rats.
AB  - Inefficient alveolar wound repair contributes to the development of pulmonary
      fibrosis. Hepatocyte growth factor (HGF) is a potent growth factor for alveolar
      type II epithelial cells (AECII) and may improve repair and reduce fibrosis. We
      studied whether targeted gene transfer of HGF specifically to AECII improves lung
      fibrosis in bleomycin-induced lung fibrosis. A plasmid encoding human HGF
      expressed from the human surfactant protein C promoter (pSpC-hHGF) was designed,
      and extracorporeal electroporation-mediated gene transfer of HGF specifically to
      AECII was performed 7 days after bleomycin-induced lung injury in the rat.
      Animals were killed 7 days after hHGF gene transfer. Electroporation-mediated HGF
      gene transfer resulted in HGF expression specifically in AECII at biologically
      relevant levels. HGF gene transfer reduced pulmonary fibrosis as assessed by
      histology, hydroxyproline determination, and design-based stereology compared
      with controls. Our results indicate that the antifibrotic effect of HGF is due in
      part to a reduction of transforming growth factor-beta(1), modulation of the
      epithelial-mesenchymal transition, and reduction of extravascular fibrin
      deposition. We conclude that targeted HGF gene transfer specifically to AECII
      decreases bleomycin-induced lung fibrosis and may therefore represent a novel
      cell-specific gene transfer technology to treat pulmonary fibrosis.

PMID- 23134112
TI  - Twin pregnancy and congenital cytomegalovirus: case report and review.
AB  - Primary cytomegalovirus (CMV) infection during pregnancy is the leading
      infectious cause of congenital neurological disabilities. Diagnosis of maternal
      primary CMV infection and fetal compromise can be difficult, as well as the fact
      that most infected child are asymptomatic at birth, which makes binomial CMV and
      pregnancy challenging. The treatment of pregnant women with CMV
      hyperimmunoglobulin (CMV-HIG) has shown promising results. However, as far as we
      know, no randomized trials of immunoglobulin therapy of CMV-infected fetuses are
      ongoing. We describe CMV-HIG administration for twin pregnancy as maternal and
      fetal infection early in gestation. The epidemiology, clinical manifestations,
      prevention strategies and treatment of CMV infections are reviewed.

PMID- 23134113
TI  - Differential gene expression in human fibroblasts after alpha-particle emitter
      (211)At compared with (60)Co irradiation.
AB  - PURPOSE: The aim of this study was to identify gene expression profiles
      distinguishing alpha-particle (211)At and (60)Co irradiation. MATERIALS AND
      METHODS: Gene expression microarray profiling was performed using total RNA from
      confluent human fibroblasts 5 hours after exposure to (211)At labeled trastuzumab
      monoclonal antibody (0.25, 0.5, and 1 Gy) and (60)Co (1, 2, and 3 Gy). RESULTS:
      We report gene expression profiles that distinguish the effect different
      radiation qualities and absorbed doses have on cellular functions in human
      fibroblasts. In addition, we identified commonly expressed transcripts between
      (211)At and (60)Co irradiation. A greater number of transcripts were modulated by
      (211)At than (60)Co irradiation. In addition, down-regulation was more prevalent
      than up-regulation following (211)At irradiation. Several biological processes
      were enriched for both irradiation qualities such as transcription, cell cycle
      regulation, and cell cycle arrest, whereas mitosis, spindle assembly checkpoint,
      and apoptotic chromosome condensation were uniquely enriched for alpha particle
      irradiation. CONCLUSIONS: LET-dependent transcriptional modulations were observed
      in human fibroblasts 5 hours after irradiation exposure. These findings suggest
      that in comparison with (60)Co, (211)At has the clearest influence on both tumor
      protein p53-activated and repressed genes, which impose a greater overall burden
      to the cell following alpha particle irradiation.

PMID- 23134115
TI  - Structure and protein composition of a basal-body scaffold ("cage") in the
      hypotrich ciliate Euplotes.
AB  - Cilia on the ventral surface of the hypotrich ciliate Euplotes are clustered into
      polykinetids or compound ciliary organelles, such as cirri or oral membranelles,
      used in locomotion and prey capture. A single polykinetid may contain more than
      150 individual cilia; these emerge from basal bodies held in a closely spaced
      array within a scaffold or framework structure that has been referred to as a
      basal-body "cage". Cage structures were isolated free of cilia and basal bodies;
      the predominant component of such cages was found on polyacrylamide gels to be a
      45-kDa polypeptide. Antisera were raised against this protein band and used for
      immunolocalizations at the light and electron microscope levels. Indirect
      immunofluorescence revealed the 45-kDa polypeptide to be localized exclusively to
      the bases of the ventral polykinetids. Immunogold staining of thin sections of
      intact cells further localized this reactivity to filaments of a double-layered
      dense lattice that appears to link adjoining basal bodies into ordered arrays
      within each polykinetid. Scanning electron microscopy of isolated cages reveals
      the lower or "basal" cage layer to be a fine lacey meshwork supporting the basal
      bodies at their proximal ends; adjoining basal bodies are held at their
      characteristic spacing by filaments of an upper or "medial" cage layer. The
      isolated cage thus resembles a miniature test-tube rack, able to accommodate
      varying arrangements of basal-body rows, depending on the particular type of
      polykinetid. Because of its clear and specific localization to the basal-body
      cages in Euplotes, we have termed this novel 45-kDa protein "cagein".

PMID- 23134117
TI  - Flexible imaging color enhancement improves visibility of transnasal endoscopic
      images in diagnosing esophageal varices: a multicenter prospective blinded study.
AB  - OBJECTIVE: To clarify the usefulness of transnasal esophagogastroduodenoscope (N
      EGD) with all flexible imaging color enhancement (FICE) patterns (0-9) for the
      diagnosis of esophageal varices (EV). METHODS: A total of 50 patients with EV
      were examined during the same period by N-EGD without sedation and by peroral
      endoscopy (O-EGD) with sedation. The visibility of treatment scars, microvessels,
      recurrent EV and red color sign (RCS) were measured. Visibility was evaluated by
      five blinded observers (poor-good: 0-10), and the effect of both endoscopic
      examinations on the cardiorespiratory function of the patients was measured.
      RESULTS: The image scores for O-EGD and N-EGD with ordinary mode and N-EGD with
      FICE were 7.3 +/- 1.2, 6.1 +/- 1.0 and 6.9 +/- 1.0 for treatment scars; 7.2 +/-
      1.4, 6.2 +/- 1.2 and 7.3 +/- 1.0 for microvessels; 7.2 +/- 1.2, 6.1 +/- 1.0 and
      7.1 +/- 1.0 for recurrent EV and 7.2 +/- 1.3, 6.1 +/- 1.3, and 7.2 +/- 1.2 for
      RCS, respectively (intraclass correlation coefficients > 0.6). When FICE patterns
      2, 6 and 9 were used, visibility was much improved. Ten minutes after insertion,
      the double product values in the N-EGD with the FICE group were significantly
      better (P < 0.05). CONCLUSIONS: N-EGD with FICE is very useful for the diagnosis
      of EV and can improve the visibility of N-EGD on each lesion to the same level as
      that of O-EGD. N-EGD with FICE does not require sedation and may reduce the risk
      of hepatic encephalopathy.

PMID- 23134118
TI  - Robot-assisted intracorporeal formation of the ileal neobladder.
AB  - We are celebrating the 10th anniversary of robot-assisted laparoscopic radical
      cystectomy (RARC) with urinary diversion (UD), and it seems that this operation
      is successfully following the footsteps of robot-assisted laparoscopic radical
      prostatectomy. Until now, approximately 1000 RARCs have been recorded; of them,
      only 102 were performed totally intracorporeally with a formation of an ileal
      neobladder. Despite the small numbers, morbidity and functional outcomes seem to
      be acceptable, when compared with the gold standard-the open procedure. It is
      imperative that in a challenging procedure such as this, the console surgeon
      follow a standardized protocol of all surgical steps to ensure the optimal
      results. In this article, we are sharing Karolinska's experience and discuss all
      perioperative issues along with ways of dealing with tricky cases.

PMID- 23134119
TI  - A ClpB chaperone knockout mutant of Mesorhizobium ciceri shows a delay in the
      root nodulation of chickpea plants.
AB  - Several molecular chaperones are known to be involved in bacteria stress
      response. To investigate the role of chaperone ClpB in rhizobia stress tolerance
      as well as in the rhizobia-plant symbiosis process, the clpB gene from a chickpea
      microsymbiont, strain Mesorhizobium ciceri LMS-1, was identified and a knockout
      mutant was obtained. The ClpB knockout mutant was tested to several abiotic
      stresses, showing that it was unable to grow after a heat shock and it was more
      sensitive to acid shock than the wild-type strain. A plant-growth assay performed
      to evaluate the symbiotic performance of the clpB mutant showed a higher
      proportion of ineffective root nodules obtained with the mutant than with the
      wild-type strain. Nodulation kinetics analysis showed a 6- to 8-day delay in
      nodule appearance in plants inoculated with the DeltaclpB mutant. Analysis of
      nodC gene expression showed lower levels of transcript in the DeltaclpB mutant
      strain. Analysis of histological sections of nodules formed by the clpB mutant
      showed that most of the nodules presented a low number of bacteroids. No
      differences in the root infection abilities of green fluorescent protein-tagged
      clpB mutant and wild-type strains were detected. To our knowledge, this is the
      first study that presents evidence of the involvement of the chaperone ClpB from
      rhizobia in the symbiotic nodulation process.

PMID- 23134120
TI  - Discovery and pharmacological evaluation of a diphenethylamine derivative
      (HS665), a highly potent and selective kappa opioid receptor agonist.
AB  - Here we report on the design, synthesis, and biological characterization of novel
      kappa opioid (KOP) receptor ligands of diphenethylamines. In opioid receptor
      binding and functional assays, the N-cyclobutylmethyl substituted derivative 4
      (HS665) showed the highest affinity and selectivity for the KOP receptor and KOP
      agonist potency. Compound 4 inhibited acetic acid induced writhing after
      subcutaneous administration in mice via KOP receptor-mediated mechanisms, being
      equipotent as an analgesic to the KOP agonist U50,488.

PMID- 23134122
TI  - Cantilever magnetometry of individual Ni nanotubes.
AB  - Recent experimental and theoretical work has focused on ferromagnetic nanotubes
      due to their potential applications as magnetic sensors or as elements in high
      density magnetic memory. The possible presence of magnetic vortex states-states
      which produce no stray fields-makes these structures particularly promising as
      storage devices. Here we investigate the behavior of the magnetization states in
      individual Ni nanotubes by sensitive cantilever magnetometry. Magnetometry
      measurements are carried out in the three major orientations, revealing the
      presence of different stable magnetic states. The observed behavior is well
      described by a model based on the presence of uniform states at high applied
      magnetic fields and a circumferential onion state at low applied fields.

PMID- 23134121
TI  - Characterization of EstCOo8 and EstC34, intracellular esterases, from the wine
      associated lactic acid bacteria Oenococcus oeni and Lactobacillus hilgardii.
AB  - AIM: To clone and characterize two related intracellular esterases from
      Oenococcus oeni and Lactobacillus hilgardii under wine-like conditions. METHODS
      AND RESULTS: The published genome sequences for O. oeni and Lact. hilgardii were
      used to identify, clone and purify putative esterase genes from these species
      designated EstCOo8 and EstC34, respectively. Both esterases are members of family
      V of lipolytic enzymes. However, EstC34 contains an SGSLG nucleophilic elbow
      structural motif instead of the usual GGSLG motif which is conserved in other
      lactic acid bacteria. Both esterases exhibited greatest specificity for C(2) 
      C(4) pNP-linked substrates and retained activity under wine-like conditions.
      EstCOo8 had an optimum temperature, pH, and ethanol concentration of 40 degrees
      C, 5.5 and 6% (v/v), respectively. Whereas EstC34 had an optimum temperature, pH
      and ethanol concentration of 50 degrees C, 5.0 and 10% (v/v), respectively.
      CONCLUSIONS: Both esterases were stable and retained activity under conditions
      that would be encountered in wine. They have the potential to reduce short-chain
      ethyl esters such as ethyl acetate. SIGNIFICANCE AND IMPACT OF THE STUDY: This
      study provides information that might help improve the performance of LAB during
      malolactic fermentation in wine in the future, either by strain selection,
      optimization or direct enzyme addition.

PMID- 23134127
TI  - Psychiatric readmission: an integrative review of the literature.
AB  - BACKGROUND: In the global context of contemporary psychiatric
      deinstitutionalization, the phenomenon of psychiatric readmission imposes
      important challenges, as it exposes the fragility of the network of mental health
      services. AIMS: To gather, synthesize and analyse the national and international
      scientific literature regarding the phenomenon of psychiatric readmission in the
      context of deinstitutionalization. METHODS: Through the combination of
      descriptors, an integrative review was performed of publications from the period
      1997 to 2010 included in the MedLine, PubMed, LILACS, SciELO and PsycINFO
      databases. Selection of the articles was based on pre-established inclusion and
      exclusion criteria. Three authors independently evaluated the eligibility of the
      articles. The level of inter-judge concordance was calculated, using the formula:
      agreement = Sigma possible concordance subtracted from real discordance divided
      by the number of articles. Information about the selected studies was
      systematized and analysed. FINDINGS: Sixteen articles met the inclusion criteria.
      Studies conducted and published in international journals, mainly in the USA,
      with a quantitative approach predominated. In general, the studies addressed the
      phenomenon of psychiatric readmission after the restructuring of mental health
      care. The variables investigated were clinical and sociodemographic factors and
      the characteristics of the mental health service associated with readmission, as
      well as the programs developed specifically for patients vulnerable to hospital
      readmissions. CONCLUSIONS: It was noted that the perspective of the patient
      regarding their readmissions, as well as the interface with the social and
      familial context in which they maintain their social relationships and care for
      their health, was largely unexplored by the literature.

PMID- 23134123
TI  - The enzymology of a viral genome packaging motor is influenced by the assembly
      state of the motor subunits.
AB  - Terminase enzymes are responsible for the excision of a single genome from a
      concatemeric precursor (genome maturation) and concomitant packaging of DNA into
      the capsid shell. Here, we demonstrate that lambda terminase can be purified as a
      homogeneous "protomer" species, and we present a kinetic analysis of the genome
      maturation and packaging activities of the protomeric enzyme. The protomer
      assembles into a distinct maturation complex at the cos sequence of a concatemer.
      This complex rapidly nicks the duplex to form the mature left end of the viral
      genome, which is followed by procapsid binding, activation of the packaging
      ATPase, and translocation of the duplex into the capsid interior by the terminase
      motor complex. Genome packaging by the protomer shows high fidelity with only the
      mature left end of the duplex inserted into the capsid shell. In sum, the data
      show that the terminase protomer exhibits catalytic activity commensurate with
      that expected of a bone fide genome maturation and packaging complex in vivo and
      that both catalytically competent complexes are composed of four terminase
      protomers assembled into a ringlike structure that encircles duplex DNA. This
      work provides mechanistic insight into the coordinated catalytic activities of
      terminase enzymes in virus assembly that can be generalized to all of the double
      stranded DNA viruses.

PMID- 23134128
TI  - Private duty nurses in Greek hospitals: a literature review.
AB  - AIM: The study aims to provide an overview of the practice of private duty nurses
      in Greek hospitals. BACKGROUND: For several decades, it has been a necessity for
      some hospital patients to hire private duty nurses (PDNs) to counterbalance the
      inadequacies of hospital infrastructures. In the current economic crisis in
      Greece, the majority of patients will not be able to afford to pay for private
      nursing care. METHODS: Databases such as PubMed, CINAHL, ScienceDirect, Wiley
      Online Library, Google Scholar and national sources were searched for relevant
      literature through a range of keywords. Information gathered was evaluated for
      relevance and grouped on a thematic basis. FINDINGS: Five articles met the
      inclusion criteria. Nearly 90% of PDNs have secondary levels of education or
      below. Approximately 15% of patients use PDNs at night due to nurse shortages and
      inability of their families to stay with them. Fifty per cent of the relatives
      reported being very unsatisfied with PDN services, while the cost for the use of
      a PDN is rather high. CONCLUSION: The existence of private duty nursing has been
      largely responsible for protecting healthcare authorities from the need to
      develop effective care infrastructures. In the current economic climate, nursing
      and healthcare authorities must staff wards appropriately for safe, free and
      efficient care for all patients. Effective utilization of the national nursing
      and healthcare workforce--including PDNs with appropriate qualifications--and
      matching demand with the necessary skills is essential.

PMID- 23134129
TI  - In-hospital paediatric accidents: an integrative review of the literature.
AB  - BACKGROUND: Paediatric hospitals can be perceived by children, parents, health
      professionals as 'safe' places, but accidents do occur. AIM: To review
      publications relating to in-hospital paediatric accidents and highlight the state
      of-the-science concerning this issue especially in relation to falls, and the
      evolution of research addressing this issue. METHODS: Integrative review of
      papers published before March 2011 on accidents and falls occurred in
      hospitalized children. Electronic databases (PubMed, Cumulative Index to Nursing
      and Allied Health Literature and Cochrane Library databases) and further hand
      searching through references were searched. The inclusion criteria were articles
      involving observational, quasi-experimental or experimental studies in English or
      Italian. Exclusion criteria were articles addressing the outcomes of falls caused
      by suspect violence on children. Thirteen studies in English were included.
      RESULTS: Of the 13 studies conducted between 1963 and 2010, 10 had been conducted
      in the last 5 years; 10 in the USA. The studies were divided into two categories:
      contextualization and prevention of the 'accident' or 'fall' phenomenon (10
      studies), and fall risk assessment (three studies). The most frequent type of
      design was observational explorative/descriptive. Several areas of investigation
      were explored (hazardous environment, children's characteristics correlated to
      accidents/falls, characteristics of the accidents/falls and their outcomes,
      paediatric fall risk factors and risk assessment tools, fall risk prevention
      programmes, parents' perceptions of accident/fall risks, etc.). DISCUSSION: No
      comparable methods were used to investigate the contextualization and prevention
      of the 'accident' and 'fall' phenomena; proposed fall risk assessment tools were
      not evaluated for their reliability and validity. CONCLUSIONS: Consensus would be
      needed around the approach to accidents in terms of: the definition of 'accident'
      and 'fall'; 'fall-related injury' and respective classifications; the frequency
      and rate calculation methods; the tools used to assess the risk of falls; and
      evidence-based practice aimed at preventing them.

PMID- 23134130
TI  - Strategies to support breastfeeding: a review.
AB  - BACKGROUND: Mothers need to be given support, confidence and encouragement to
      successful breastfeeding. The importance of breastfeeding support has been
      addressed in numerous studies. However, reviews to explore strategies to support
      breastfeeding are sparse. AIM: The study aims to explore strategies to support
      breastfeeding. It was also aimed to reveal how the international papers compare
      with the Turkish situation. METHODS: Searches of CINAHL, PubMed, ScienceDirect,
      Scopus, Web of Science databases, Cochrane databases, Turkish health databases
      were conducted for data collection. The search was limited to articles published
      between the years 1995 and 2011, focusing on the strategies related to the
      support received by mothers. Two experts independently read and analysed 38
      articles. FINDINGS: Thirty-eight papers were included in this review. The
      findings identified strategies to support breastfeeding. These include
      collaboration with community and family members; confidence building; appropriate
      ratio of staffing levels; development of communication skills; and 'closing the
      gap' in inequalities in health. CONCLUSION: Mothers benefit from strategies that
      encourage breastfeeding, with guidance that supports their self-efficacy and
      feelings of being capable and empowered, and is tailored to their individual
      needs.

PMID- 23134131
TI  - Strategies for health education in North American immigrant populations.
AB  - AIM: This article is intended to stimulate critical thinking about barriers and
      strategies related to health education for immigrant populations. Its rationale
      is to promote an understanding and appreciation for the individuality and
      diversity of immigrant beliefs, values and culture, and how these contribute to
      health education through nursing practice, research and theory. BACKGROUND: Since
      2005, over 1,250,000 immigrants annually have obtained legal permanent residence
      in North America [over 1 million annually in the United States of America (USA)
      and over 250,000 annually in Canada]. THE PROBLEM: While a broad immigration
      policy leads to population growth, cultural change and ethnic diversity,
      migration impacts immigrants' health status. In North America, the 'healthy
      immigrant effect', whereby immigrants generally tend to be healthier than
      individuals born in host countries, steadily declines after immigration. METHODS:
      Immigration statistics and reports on literacy and learning were sourced from
      official websites in Canada and the USA. These were reviewed and discussed in the
      context of scholarly published literature on health literacy, health education
      and health promotion. OPPORTUNITIES: Promoting health in immigrant populations is
      difficult due to cultural, linguistic, health literacy and socio-economic
      barriers. Cultural sensitivity, careful inquiry and comprehensive knowledge of
      immigrants' social circumstances are essential to every health education
      programme. CONCLUSION: Strategies for immigrant health education must be
      technologically diverse, involve partnerships with multidisciplinary
      professionals, elicit active community participation, and facilitate language
      transfer and interpretation. Future research must continue to explore these
      barriers and strategies, using both qualitative and quantitative methodologies.

PMID- 23134132
TI  - Challenges in sharing knowledge: reflections from the perspective of an
      expatriate nurse working in a South Sudanese hospital.
AB  - AIM: This account, based on the experience of the first author, aims to describe
      an example of practice from a hospital in South Sudan. The example illustrates a
      cross-cultural encounter and the challenges that a Sudanese nurse and an
      expatriate nurse face in sharing knowledge when providing patient care. CONTENT:
      The constructed practical example between nurses with different knowledge bases
      and experiences was characterized by the expatriate nurse giving her instructions
      and not allowing the Sudanese nurse to respond to them. This 'one-way'
      communication demonstrated that the expatriate nurse considered herself to have
      the better knowledge of nursing care. These aspects of the encounter formed the
      basis for the following discussion, which sheds light on how the expatriate nurse
      ideally could have worked by using a dialogue instead of one-way communication.
      The importance of having knowledge and understanding of the context in cross
      cultural encounters was also emphasized. CONCLUSIONS: The discussion of this
      practical example can provide insight for other nurses when working in cultures
      other than their own into the importance of using a dialogue when sharing
      knowledge in a cross-cultural encounter. In addition, expatriates can be made
      aware of the importance of acquiring knowledge about the context for 'the other'
      when working cross culturally. Finally, it should be noted that the description
      and discussion of the experience reflect only the perspective of the expatriate
      nurse.

PMID- 23134133
TI  - A critical analysis of undergraduate students' cultural immersion experiences.
AB  - PURPOSE: This paper is concerned with the impact of an international health
      promotion experience on the understanding of culture among university students.
      Such immersion experiences are often cited as a strategy to prepare nurses for
      culturally appropriate practice. We describe students' epistemic movements over
      time with respect to cultural perspectives prior to, during and after a field
      study in Malawi. DESIGN: Data were collected at three time points from students
      in undergraduate nursing (n = 14) and non-nursing (n = 8) programs at a Canadian
      university. Two essays narrating participants' understanding of culture were
      submitted by consenting class members. A subgroup of nine participants (four
      nursing students, five from other disciplines) completed a third narrative
      following a subsequent field study course in Malawi. METHOD: Using narrative
      analysis, themes and structures in the participants' writing were identified and
      located within a constructivist or essentialist paradigm of cultural
      understanding. FINDINGS: Overwhelmingly, students' narratives were initially
      portrayed and informed by an essentialist understanding of culture. Later
      narratives demonstrated varying degrees of epistemic movement towards more
      constructivist viewpoints. Narratives that initially exhibited constructivist
      characteristics tended to display strengthened convictions in that paradigm.
      CONCLUSION: We challenge the claim that an international immersion experience
      immediately transforms participants into cultural experts; our evidence suggests
      that students experienced existential growth, but their understanding of culture
      did not change as a result of their brief stay in a different cultural context.
      Cultural immersion is a phenomenon that requires more critical analysis and
      systematic investigation to determine how such experiences contribute to learning
      about culture among nursing students.

PMID- 23134135
TI  - Nurse scholars' knowledge and use of electronic theses and dissertations.
AB  - BACKGROUND: Electronic theses and dissertations (ETDs) are a valuable resource
      for nurse scholars worldwide. ETDs and digital libraries offer the potential to
      radically change the nature and scope of the way in which doctoral research
      results are presented, disseminated and used. An exploratory study was undertaken
      to better understand ETD usage and to address areas where there is a need and an
      opportunity for educational enhancement. AIMS: The primary objective was to gain
      an initial understanding of the knowledge and use of ETDs and digital libraries
      by faculty, graduate students and alumni of graduate programs at schools of
      nursing. DESIGN: A descriptive online survey design was used. METHODS: Purposeful
      sampling of specific schools of nursing was used to identify institutional
      participants in Australia, New Zealand, the UK and the US. A total of 209
      participants completed the online questionnaire. RESULTS: Only 44% of
      participants reported knowing how to access ETDs in their institutions' digital
      libraries and only 18% reported knowing how to do so through a national or
      international digital library. Only 27% had cited an ETD in a publication. The
      underuse of ETDs was found to be attributable to specific issues rather than
      general reluctance to use online resources. CONCLUSIONS: This is the first
      international study that has explored awareness and use of ETDs, and ETD digital
      libraries, with a focus on nursing and has set the stage for future research and
      development in this field. Results show that most nursing scholars do not use
      ETDs to their fullest potential.

PMID- 23134134
TI  - Immersion research education: students as catalysts in international
      collaboration research.
AB  - BACKGROUND: This paper describes an international nursing and health research
      immersion program. Minority students from the USA work with an international
      faculty mentor in teams conducting collaborative research. The Minority Health
      International Research Training (MHIRT) program students become catalysts in the
      conduct of cross-cultural research. AIM: To narrow the healthcare gap for
      disadvantaged families in the USA and partner countries. METHODS: Faculty from
      the USA, Germany, Italy, Colombia, England, Austria and Thailand formed an
      international research and education team to explore and compare family health
      issues, disparities in chronic illness care, social inequities and healthcare
      solutions. USA students in the MHIRT program complete two introductory courses
      followed by a 3-month research practicum in a partner country guided by faculty
      mentors abroad. The overall program development, student study abroad
      preparation, research project activities, cultural learning, and student and
      faculty team outcomes are explored. RESULTS: Cross-fertilization of research,
      cultural awareness and ideas about improving family health occur through
      education, international exchange and research immersion. Faculty research and
      international team collaboration provide opportunities for learning about
      research, health disparities, cultural influences and healthcare systems. The
      students are catalysts in the research effort, the dissemination of research
      findings and other educational endeavours. Five steps of the collaborative
      activities lead to programmatic success. CONCLUSIONS: MHIRT scholars bring
      creativity, enthusiasm, and gain a genuine desire to conduct health research
      about families with chronic illness. Their cultural learning stimulates career
      plans that include international research and attention to vulnerable
      populations.

PMID- 23134136
TI  - Undergraduate nursing education reform in France: from vocational to academic
      programmes.
AB  - BACKGROUND: France is currently implementing a number of reforms to the
      healthcare and education systems. Within this context, a comprehensive reform of
      undergraduate nurse education was launched in 2009, bringing nurse education
      closer to the higher education environment. It is likely in future to move from
      being vocational towards becoming an academic educational programme. AIM: In this
      paper, the 2009 reform of the French pre-registration nursing curriculum will be
      analysed in light of the European framework. PROCESS: The pedagogical approach,
      methods and content of nursing education in France are undergoing an in-depth
      reorganization. The main innovation that the reforms introduce is a competency
      based approach. France is joining the group of countries that require first
      degree-level entry to the nursing profession. CONCLUSION: There are still many
      unanswered questions regarding the competencies and qualifications required by
      both the academic and clinical educators many of whom have not been previously
      involved in research or publications. The future status of nursing science is
      unclear, as is the way in which the nursing profession will be able to retain
      control over its educational mechanisms.

PMID- 23134137
TI  - A comparison of student motivation in selecting bachelors of nursing or
      paediatric nursing at an Italian university.
AB  - AIM: To investigate students' reasons for choosing general or paediatric nursing,
      and to compare motivation factors and personal characteristics between the two
      professions. BACKGROUND: In Italy, nursing students can choose between two
      distinct career paths: general and paediatric nursing. However, it is unclear
      what factors motivate a student to choose between these two pathways. METHODS: A
      cross-sectional approach was used to compare a sample of general and paediatric
      nursing students enrolled in a university in northeast Italy. We administered a
      questionnaire that covered socio-demographic characteristics and included an
      instrument of motivation developed by Zysberg & Berry to 224 students enrolled in
      the 3-year classes. RESULTS: We analysed 215 questionnaires (96%). Paediatric
      nurses were generally younger, had attended a college preparatory high school and
      had previously failed another university programme. Many students, in both
      groups, had a relative who was a nurse, or had cared for a sick friend or family
      member. Students did not vary significantly in how they evaluated items included
      in the questionnaire. CONCLUSION: A career in nursing should be advised for
      students who are motivated to help other people. Paediatric nursing was
      identified as an acceptable career choice by students of college preparatory high
      schools or by students who had initially enrolled in a different university
      programme. General nursing was a satisfactory choice by students with previous
      work experience.

PMID- 23134138
TI  - The effect of a structured empathy course on the students of a medical and a
      nursing school.
AB  - AIM: The study aims to determine the effect of an empathy course for medical and
      nursing school students in one university in Turkey. Being able to relate to
      others empathetically is important for health professionals who need to develop
      therapeutic relationships with people who are sick, weak, sensitive and
      vulnerable. Professionals need empathic communication skills and professionalism
      not only for patients and their families but also for colleagues and other
      members of the health team. METHOD: All first year students (257) from a medical
      and a nursing school in one Turkish university in 2008-2009 and 2009-2010 were
      enrolled to the study. The course included 10 h of lectures on empathy and
      communication skills given through five consecutive weeks with 2 h in a week in
      the first year of both schools. Data were collected by using the Empathic
      Communication Skills Scale (ECSS), and the Empathic Tendency Scale (ETS) before
      and after the course. There were 143 medical students and 83 nursing students
      (total: 226, 88%) who completed the ECSS and ETS in a pre-/post-test study.
      FINDINGS: Results demonstrated that all students received significantly higher
      scores for the final application than for initial scores on both scales. This
      implied that the targeted educational programme could have a positive effect on
      learning empathy and gaining empathy skills and tendency. CONCLUSION: Effective
      educational programmes might facilitate and improve empathic skills and empathic
      tendency of medical and nursing students, and both male and female students
      benefitted from the empathy course.

PMID- 23134139
TI  - Psychological consequences of bullying for hospital and aged care nurses.
AB  - AIM: This study examines the psychological consequences of workplace bullying by
      negative affectivity (NA) and demographics for hospital and aged care nurses.
      INTRODUCTION/BACKGROUND: Nurses are particularly vulnerable to workplace
      bullying, with suggestions that oppressed group behaviours may play a role.
      Bullying is a potent stressor that can negatively impact psychological well
      being, which, with NA and demographics, may be important in understanding the
      consequences of nurse bullying. Such factors are yet to be examined together
      across different nursing contexts. METHODS: A cross-sectional survey was
      conducted across hospital and aged care nurses working within a medium to large
      Australian healthcare organization in October 2009. The sample comprised 233
      (29.1%) hospital and 208 (43.8%) aged care nurses. Analyses of covariance were
      used to evaluate the data. RESULTS: For hospital nurses, psychological distress
      was noted as an impact of bullying, while depression was the impact for aged care
      nurses. Full-time aged care nurses reporting bullying had higher psychological
      distress scores, compared with part-time workers in the same area. NA was a
      significant covariate across both outcomes in both contexts.
      DISCUSSION/CONCLUSION: This study demonstrates that bullying has detrimental
      consequences for the mental health of nurses in both hospital and aged care
      contexts. The results support the suggestion that nurses are an oppressed group
      at high risk of bullying, confirm the intrinsic nature of NA to the bullying
      process, and highlight the importance of employment type for aged care nurses.
      Given the shortage of nurses, managers need to give higher priority to addressing
      workplace bullying and implementing zero tolerance policies.

PMID- 23134140
TI  - Predictors of hospital nurses' intent to stay: a cross-sectional questionnaire
      survey in Shanghai, China.
AB  - AIM: To investigate predictors of hospital nurses' intent to stay in the nursing
      profession. METHODS: A cross-sectional survey design was adopted. Over 1000
      nurses working in hospitals in Shanghai, China, were invited to complete a survey
      questionnaire between May and October 2009 and 919 nurses responded for an 82%
      response rate. FINDINGS: Regression models explained 41.3% of variance in nurse
      intent to stay. Although the proposed model hypothesized 18 predictors of intent
      to stay, only seven were statistically significant factors of nurse intent to
      stay: normative commitment, economic costs commitment, age, limited alternatives
      commitment, praise/recognition, professional advancement opportunities and the
      hospital classification. Of these, the strongest predictors were normative
      commitment, economic costs commitment and age, which explained 37.3% of variance
      in nurse intent to stay. CONCLUSION: Possible strategies to improve nurses'
      intent to stay include employment practices that improve the work environment,
      increased wages and benefits, and greater professional opportunity for nurses'
      personal growth development and promotion. Healthcare organizations should
      establish an asserting and nurturing environment for nurses and improve nurses'
      normative commitment and economic costs commitment. Increased effort should be
      made to improve nurses' conditions in primary and secondary hospitals where
      nurses report a lower level of intent to stay in nursing. STUDY LIMITATIONS:
      Participants came from a limited number of hospitals in Shanghai. A larger sample
      from different hospitals in Shanghai and other districts in Mainland China could
      have enhanced the generalizability of the results and increased the power of the
      study.

PMID- 23134141
TI  - 'Being young': a qualitative study of younger nurses' experiences in the
      workplace.
AB  - AIM: The overall goal of this study was to obtain a greater understanding of the
      experiences of nurses aged under 30 in the New Zealand workforce with a view to
      developing age-appropriate retention strategies. BACKGROUND: Nurses aged under 30
      constitute around 10% of the world's nursing workforce yet little is known about
      their experiences in the workplace. Poor retention of younger nurses is a cause
      for concern. The implications of the perceptions and needs of this generation of
      nurses must be considered in order to ensure effective succession planning.
      METHODS: An explorative descriptive design framed within a broad qualitative
      methodology was utilized to explore experiences of younger nurses in the New
      Zealand workforce. Data were analysed thematically. FINDINGS AND DISCUSSION:
      Findings are reported under five themes: challenges of nursing, rewards of
      nursing, being young, coping and addressing generational differences. The study
      provides new knowledge about the experiences of younger nurses in the workforce
      and in particular the challenges facing younger Asian nurses. CONCLUSIONS:
      Managers and nurse leaders must address broader workforce issues as well as
      improving support for younger nurses to help improve younger nurse retention.
      Strategies designed to extend and challenge younger nurses in the workplace such
      as professional development and project work will also help, but will only be
      effective if nurses are given sufficient paid time to undertake this work. Being
      Asian provides added challenges for younger nurses in New Zealand and further
      research into the experiences of this subgroup is highly recommended.

PMID- 23134142
TI  - Professional identity and nursing: contemporary theoretical developments and
      future research challenges.
AB  - AIM: We propose that the conceptual orientation of professional identity is a
      logical consequence of self-concept development by focusing on career and its
      meaning and presents a measurable set of concepts that can be manipulated to
      improve retention of student and registered nurses within health service.
      BACKGROUND: Although professional identity is a term that is commonly written of
      in nursing literature, its theoretical origins remain unclear, and available
      empirical evidence of its presence or ability to change is omitted from nursing
      research. SOURCES OF EVIDENCE: We present a professional identity pathway and
      explore the factors that influence professional identity throughout a career in
      nursing. DISCUSSION: Nurses' professional identities develop throughout their
      lifetimes, from before entering nursing education, throughout their years of
      study and clinical experience, and continue to evolve during their careers.
      Education is, however, a key period as it is during this time students gain the
      knowledge and skills that separate nurses as professional healthcare workers from
      lay people. CONCLUSION: Finally, a call for longitudinal studies of students to
      graduates, using conceptually derived and psychometrically proven instruments
      capable of detecting the subtle changes in the construct over time, is
      recommended. Further empirical research into the theoretical concepts that
      underline professional identity, and the factors that influence changes in this
      important construct in nursing, is required. Ultimately, the practical relevance
      of such research will lie in the potential it provides for enhanced nursing
      career support and improved workforce policies.

PMID- 23134143
TI  - Validity and reliability of the Turkish version of the Essentials of Magnetism
      Scale (EOM II).
AB  - AIM: To test the validity and reliability of the Turkish version of the
      Essentials of Magnetism II Scale (EOMII) for use by staff nurses as being
      essential to quality patient care. METHODS: This study consisted of 385 nurses
      from four joint commission internationally accredited hospitals. The EOMII scale
      was translated using a back-translation technique. The statistical analysis was
      carried out using Cronbach's alpha to test the internal consistency of the scale,
      while the factor analysis was carried out using the principal component analysis
      together with the varimax rotation and Kaiser normalization to test its construct
      validity. RESULTS: The total mean scores of all the items of the scale were found
      to be 155.33 (minimum 77 - maximum 219) and the standard deviation was 29.45. All
      the items showed a statistically significant correlation (P < 0.01). The
      Cronbach's alpha of the scale was 0.92, indicating a high level of reliability.
      Cronbach's alpha consistencies in subgroups were between 0.87 and 0.70. In this
      study, job satisfaction and quality results show the sign of convergence as in
      the original scale, which shows that the scale has a high construct validity (P <
      0.01). DISCUSSIONS: Transcultural differences in the quality of nursing services
      can only be compared with reliable and valid instruments. This study shows that
      the Turkish version of the EOMII scale is a valid and reliable instrument to
      assess the nurses' working environment and to provide quality patient care in
      Turkey.

PMID- 23134144
TI  - Decreased nerve growth factor upregulation is a mechanism for reduced mechanical
      hyperalgesia after the second bout of exercise in rats.
AB  - Delayed onset muscle soreness (DOMS) is reduced when the same exercise is
      repeated after a certain interval. However, the mechanism for this adaptation,
      called a repeated bout effect, is still not well understood. Recently, we showed
      that upregulated nerve growth factor (NGF) triggered by B2 bradykinin receptor
      (B2R) activation in exercised muscle was responsible for DOMS. In this study, we
      investigated whether NGF upregulation was reduced after repeated bouts of
      exercise in rats, and if so, whether this change occurred upstream of B2R. A bout
      of 500 lengthening contractions (LC) was applied on day 0 and again 5 days later.
      DOMS was evaluated by the mechanical withdrawal threshold of the exercised
      extensor digitorum longus (EDL) muscle. Mechanical hyperalgesia and NGF mRNA
      upregulation in EDL were observed after the first LC, but not after the second
      LC. We then injected HOE140, a B2R antagonist with effects lasting only several
      hours, once before the first LC. This blocked the development of mechanical
      hyperalgesia and NGF mRNA upregulation not only after the first LC but also after
      the second LC. This suggests that adaptation occurred upstream of B2R, as the
      influence of the first LC was limited to that area by HOE140.

PMID- 23134145
TI  - Transcatheter arterial embolization followed by octreotide and celecoxib
      synergistically prolongs survival of rabbits with hepatic VX2 allografts.
AB  - OBJECTIVE: To validate the efficacy of an innovative multimodality therapy with
      transcatheter arterial embolization (TAE) plus octreotide and celecoxib in
      reducing neoangiogenesis and prolonging the survival of rabbits with
      hepatocellular carcinoma. METHODS: Rabbits with hepatic VX2 allografts were
      divided into four groups: control group, TAE group, octreotide + celecoxib (O +
      C) group and the multimodality therapy (TAE + O + C) group. Survival of the
      rabbits was analyzed using the Kaplan-Meier method and the expression of CD31 in
      tumor tissues was detected by immunohistochemistry. RESULTS: Rabbits in the TAE +
      O + C group lived nearly 20 days longer than those in the control group. The
      survival rate of the TAE + O + C group was 50% at day 80 and was the highest
      among the four groups (P < 0.05). No VX2 allograft-bearing rabbits in the control
      group lived longer than 60 days. Compared with the control group, the survival
      time of the other two intervention groups were not prolonged significantly (P >
      0.05). The CD31 expression induced by TAE was reduced significantly in TAE + O +
      C group (P < 0.05). Less metastasis was detected in TAE + O + C group.
      CONCLUSION: TAE followed by the long-term administration of octreotide and
      celecoxib can synergistically prolong the survival of rabbits with hepatic VX2
      allografts by inhibiting potential neoangiogenesis, tumor growth and metastasis.

PMID- 23134146
TI  - Continuous exercise training and curcumin attenuate changes in brain-derived
      neurotrophic factor and oxidative stress induced by lead acetate in the
      hippocampus of male rats.
AB  - CONTEXT: For many years it has been known that lead is life-threatening, not only
      as an air pollutant but also because of it has been associated with several
      conditions including neurodegenerative disease. Curcumin (the principal
      curcuminoid found in turmeric) has demonstrated potent antioxidant properties.
      OBJECTIVE: We investigated neuroprotective effects of endurance exercise and/or
      curcumin on lead acetate-induced neurotoxicity in the rat hippocampus. MATERIALS
      AND METHODS: Forty male Wistar rats were randomly divided into five groups: 1)
      lead acetate, 2) curcumin, 3) training, 4) training + curcumin, and 5) control.
      The rats in the training groups performed treadmill running five times a week for
      8 weeks (15-22 m/min, 25-64 min). All groups except control received lead acetate
      (20 mg/kg), whereas the control group received curcumin solution (ethyl oleate).
      In addition, the curcumin and training + curcumin groups received curcumin
      solution (30 mg/kg) intraperioneally. RESULTS: Lead acetate resulted in a
      significantly increase in the malondialdehyde (MDA) in plasma (72%), but not
      significant in hippocampus (59%). In addition, it led to significantly decreased
      brain-derived neurotrophic factor in hippocampus (17%) and total antioxidant
      capacity (27%), as compared to control group. Treadmill running, curcumin
      supplementation or both resulted in a significant decrease in hippocampus MDA
      (17, 20, 31%, respectively) and plasma MDA (60, 22, 71%) and also, significantly
      increased brain-derived neurotrophic factor (76, 45, 94%) and total antioxidant
      capacity (47.13, 47.11, 61%) levels, as compared to lead acetate group.
      DISCUSSION AND CONCLUSION: These results provide a rationale for an inhibitory
      role of curcumin and regular exercise in the attenuation of lead-induced
      neurotoxicity.

PMID- 23134147
TI  - Factors related to quality of life for patients with type 2 diabetes with or
      without depressive symptoms - results from a community-based study in China.
AB  - AIMS AND OBJECTIVES: To explore the factors related to quality of life for
      patients with type 2 diabetes with or without depressive symptoms in China.
      BACKGROUND: In patients with type 2 diabetes with or without depressive symptoms,
      different factors such as gender, social context or regional setting may affect
      their quality of life. DESIGN: This was a cross-sectional study. METHODS: Of 791
      registered patients with type 2 diabetes from four communities in Beijing,
      cluster sampling was used to recruit patients for participation. Self-rating
      depression scale was used to screen for depressive symptoms; demographic and
      clinical data were collected, and quality of life and social support were
      assessed using appropriate tools. The factors associated with quality of life
      were tested using multivariate linear regression. RESULTS: The prevalence of
      depressive symptoms in 667 patients with diabetes was 44.2%. Quality of life of
      patients with depressive symptoms was worse than that of patients without
      depressive symptoms, and this was associated negatively with history of diabetic
      complications, usage of hypoglycaemic agents or insulin and self-rating
      depression scale scores and positively with salary and subjective social support.
      CONCLUSIONS: The factors related to quality of life for patients with or without
      depressive symptoms are different. For patients with depressive symptoms, better
      salary and subjective social support are associated positively with their quality
      of life, while the presence of diabetic complications, a higher score for
      depressive symptoms and need for hypoglycaemic agents or insulin are negatively
      associated with quality of life. RELEVANCE TO CLINICAL PRACTICE: It is suggested
      that the nurse should screen depression for patients with diabetes, especially
      for those with diabetic complications or low social support. This should be done
      in the community regularly in order to find diabetic patients with depression in
      time. In addition, the results can provide a reference to clinical nursing care
      for patients with diabetes in hospitals.

PMID- 23134150
TI  - Vitamin A to prevent bronchopulmonary dysplasia: the NeoVitaA trial.

PMID- 23134151
TI  - Primary brachial vein transposition for hemodialysis access: report of a case and
      review of the literature.
AB  - The superiority of autogenous fistulae in patients with end-stage renal disease,
      performing hemodialysis, is well established and largely accepted. However, in
      case that superficial veins in the upper arm are not available for fistula
      construction, brachial vein transposition may be a viable alternative prior to
      graft placement. This transposition could be done as a primary or staged
      procedure, depending on the vein size. We present the case of a 63-year-old male
      patient with a thrombosed arteriovenous graft in the forearm and a large brachial
      vein in the ipsilateral upper arm. A one-stage (primary) brachial vein
      transposition was performed. The fistula, 10 months after its construction, is
      still patent. No complications have occurred. 

PMID- 23134152
TI  - Factors associated with increased bleeding post-endoscopic mucosal resection.
AB  - OBJECTIVE: Our aim was to identify patient and procedure characteristics that
      correlate with increased likelihood of bleeding during and after endoscopic
      mucosal resection (EMR), and thus anticipate the need for preventative therapy.
      METHODS: This was a retrospective, observational, descriptive study using a
      prospective EMR database, performed in a tertiary-care center. A total of 935 EMR
      of various locations within the gastrointestinal tract were collected. The main
      outcome measurement was early bleeding (occurring during the procedure) and
      delayed bleeding (occurring after the completion of the procedure and up to 30
      days after). RESULTS: Early bleeding occurred in 5.3% (50/935) of the procedures.
      In multivariate logistic regression analysis, esophageal EMR (OR 2.5, 95% CI 1.2
      5, P = 0.0009) and increase in lesion size (OR 1.24, 95% CI 1.1-1.5, P = 0.003)
      were both associated with higher odds of early bleeding in EMR when controlling
      for age, gender and non-steroidal anti-inflammatory drugs (NSAIDs)/clopidogrel
      use. Delayed bleeding occurred after 3.1% (n = 29) of the procedures. Of these,
      86.2% (25/29) required hospital admission and endoscopic intervention to confirm
      and/or treat bleeding site. In multivariate logistic regression analysis,
      increased lesion size (OR 1.3, 95% CI 1.1-1.5, P = 0.004) was associated with
      higher incidence of delayed bleeding post-EMR. CONCLUSIONS: In experienced hands
      bleeding during and after EMR appears to be uncommon. Larger lesions are at
      increased risk of early and delayed bleeding.

PMID- 23134153
TI  - Use of magnetic resonance imaging in the diagnosis of spinal empyema caused by a
      migrating grass awn in a dog.
AB  - Abstract CASE HISTORY: A 13 kg 3.5-year-old male neutered Cocker Spaniel
      presented with a 6-day history of deteriorating hindlimb paresis. Approximately
      10 weeks previously the owner reported removing a large number of barley grass
      seeds from the dog's coat and ears. Eight weeks later the dog was treated for
      pneumonia, based on clinical findings and thoracic radiographs. In the 4 days
      prior to referral the dog had a decreased appetite, was lethargic and appeared
      unable to urinate voluntarily. CLINICAL FINDINGS: The dog was bright and alert
      but unable to walk. Upper motor neuron signs were indicative of T3-L3 spinal
      lesion. Using magnetic resonance imaging (MRI), an abnormal low signal linear
      structure within the left T12-T13 neural foramen extending to the left lateral
      aspects of the thoracic spinal cord was detected, consistent with a foreign body.
      A left T12-T13 lateral hemilaminectomy was performed and a grass seed removed
      from a tract extending caudally from the T12-13 space, dorsal to the lumbar
      transverse processes and the rib head. The dog made a rapid recovery after
      surgery with full resolution of clinical signs. DIAGNOSIS: Spinal empyema caused
      by a migrating barley grass awn (Hordeum spp.). CLINICAL RELEVANCE: Advanced
      imaging using MRI can bea valuable method for localising foreign bodies prior to
      exploratory surgery. Animals presenting with neurological signs should have
      foreign body reactions included as a differential diagnosis.

PMID- 23134154
TI  - Uncovered self-expandable metallic stent placement as a first-line palliative
      therapy in unresectable malignant duodenal obstruction.
AB  - OBJECTIVE: To report treatment outcomes and complications of uncovered self
      expandable metallic stents (SEMS) as a first-line therapy for inoperable
      malignant duodenal obstructions in our hospital. METHODS: A retrospective
      analysis was performed in patients who had undergone placement of uncovered SEMS
      as a first-line therapy for inoperable malignant duodenal obstruction from August
      2001 to July 2011. Treatment outcomes and complications of the procedures were
      investigated. RESULTS: In total, 47 patients (25 men; mean age 65 years)
      underwent the procedure. The technical and clinical success rates were 93.6% and
      83.0%, respectively. Early complications occurred in 8 patients, including two
      guidewire-induced micro-perforations and six pancreatitis. All these 8 patients
      recovered with conservative treatment. Six late complications requiring
      additional procedures consisted of five stent occlusions due to tumor ingrowth
      and one stent migration. Four stent occlusions and one migration were treated by
      the placement of an additional covered stent and the remaining case was treated
      by balloon dilatation. The median primary stent patency period and median
      survival period after primary stent placement were 103 days and 131 days,
      respectively. CONCLUSIONS: Uncovered SEMS placement is effective as a first-line
      palliative therapy for inoperable malignant duodenal obstruction. Complications
      such as stent occlusion or migration can be easily managed with additional
      covered SEMS.

PMID- 23134155
TI  - Regulatory effects of Spirulina complex polysaccharides on growth of murine RSV-M
      glioma cells through Toll-like receptor 4.
AB  - This study is the first to report that Spirulina complex polysaccharides (CPS)
      suppress glioma growth by down-regulating angiogenesis via a Toll-like receptor 4
      signal. Murine RSV-M glioma cells were implanted s.c. into C3H/HeN mice and TLR4
      mutant C3H/HeJ mice. Treatment with either Spirulina CPS or Escherichia coli (E.
      coli) lipopolysaccharides (LPS) strongly suppressed RSV-M glioma cell growth in
      C3H/HeN, but not C3H/HeJ, mice. Glioma cells stimulated production of interleukin
      (IL)-17 in both C3H/HeN and C3H/HeJ tumor-bearing mice. Treatment with E. coli
      LPS induced much greater IL-17 production in tumor-bearing C3H/HeN mice than in
      tumor-bearing C3H/HeJ mice. In C3H/HeN mice, treatment with Spirulina CPS
      suppressed growth of re-transplanted glioma; however, treatment with E. coli LPS
      did not, suggesting that Spirulina CPS enhance the immune response.
      Administration of anti-cluster of differentiation (CD)8, anti-CD4, anti-CD8
      antibodies, and anti-asialo GM1 antibodies enhanced tumor growth, suggesting that
      T cells and natural killer cells or macrophages are involved in suppression of
      tumor growth by Spirulina CPS. Although anti-interferon-gamma antibodies had no
      effect on glioma cell growth, anti-IL-17 antibodies administered four days after
      tumor transplantation suppressed growth similarly to treatment with Spirulina
      CPS. Less angiogenesis was observed in gliomas from Spirulina CPS-treated mice
      than in those from saline- or E. coli LPS-treated mice. These findings suggest
      that, in C3H/HeN mice, Spirulina CPS antagonize glioma cell growth by down
      regulating angiogenesis, and that this down-regulation is mediated in part by
      regulating IL-17 production.

PMID- 23134157
TI  - Self-assembly of two-dimensional nanosheets induced by interfacial polyionic
      complexation.
AB  - Significant progress has been made during the past decade in preparing nanosheets
      from a wide range of materials, which are actively pursued for various
      applications such as energy storage, catalysis, sensing, and membranes. One of
      the next critical challenges is developing a robust and versatile assembly method
      which allows construction of the nanosheets into functional structures tailored
      for each specific purpose. An interesting characteristic of nanosheets is that
      they often behave as charged macromolecules and thus can readily interact with an
      oppositely charged polyelectrolyte to form a stable complex. In this report, we
      demonstrate how such a complexation process could be utilized for directing the
      self-assembly of nanosheets. By confining the nanosheet-polyelectrolyte
      complexation at air-liquid or liquid-liquid interfaces, the nanosheets are
      successfully assembled into various mesoscale architectures including fibers,
      capsules, and films. Furthermore, incorporation of additional components such as
      nanoparticles or small molecules can be easily achieved for further tailoring of
      material properties. This novel assembly method opens a pathway to many useful
      nanosheet superstructures and may be further extended to other types of
      nanomaterials in general.

PMID- 23134156
TI  - Mere15, a novel polypeptide from Meretrix meretrix, inhibits adhesion, migration
      and invasion of human lung cancer A549 cells via down-regulating MMPs.
AB  - CONTEXT: Mere15 is a novel antitumor polypeptide purified from Meretrix meretrix
      Linn. (Veneridae). Previous studies have shown that the polypeptide induced cell
      death via intrinsic mitochondrial pathway. OBJECTIVE: In the present study, the
      effects of Mere15 on cell adhesion, migration, invasion, as well as secretion and
      expression of matrix metalloproteinases (MMPs) were studied in human lung
      adenocarcinoma A549 cells. MATERIALS AND METHODS: The effect of Mere15 on cell
      adhesion, migration and invasion were studied by cell adhesion and transwell
      assay. The expression of MMPs was determined by gelatin zymography and RT-PCR
      analysis. RESULTS: The ability of cell adhesion was decreased by 86.74% at the
      concentration of 12.0 MUg/mL of Mere15. And the migration and invasion of A549
      cells were decreased with the inhibition ratio of, 69.22 and 53.84% when treated
      with 15.0 MUg/mL of Mere15. Further study also revealed that treatment of the
      cancer cells with Mere15 (15.0 MUg/mL), the secretion of MMP-2 and MMP-9 were
      down-regulated with the inhibition ratio of 72.00 and 93.24% and the inhibition
      rate of mRNA expression of MMP-2 and MMP-9 was 57.54 and 91.22%, respectively.
      DISCUSSION AND CONCLUSION: The study demonstrates that Mere15 inhibits tumor
      growth via both pro-apoptotic and antimetastasis pathways, and the polypeptide
      has potential to be developed as a multi-target therapeutic agent for the
      treatment of human lung cancer.

PMID- 23134158
TI  - Antibacterial and smear layer removal ability of a novel irrigant, QMiX.
AB  - AIM: To assess in a laboratory experimental model the efficacy of a novel root
      canal irrigant, QMiX, against Enterococcus faecalis and mixed plaque bacteria in
      planktonic phase and biofilms. In addition, its ability to remove smear layer was
      examined. METHODOLOGY: Enterococcus faecalis and mixed plaque bacteria were
      exposed to QMiX, 2% chlorhexidine (CHX), MTAD and 1% sodium hypochlorite (NaOCl)
      for 5 s, 30 s and 3 min. Following exposure, samples were taken, serially diluted
      and grown aerobically and anaerobically on tryptic soy agar (TSA) plates or on
      blood agar plates for 24 and 72 h, respectively, to measure killing of bacteria.
      E. faecalis and plaque biofilms were grown for 3 weeks on collagen-coated
      hydroxyapatite or dentine discs and exposed for 1 and 3 min to QMiX, 2% CHX,
      MTAD, 1% and 2% NaOCl. The amount of killed bacteria in biofilms was analysed by
      confocal laser scanning microscopy using viability staining. Dentine blocks were
      exposed to QMiX and 17% EDTA for 5 min. The effectiveness of smear layer removal
      by the solution was evaluated using scanning electron microscopy. For statistical
      analysis, one-way analysis of variance and comparison of two proportions were
      used. RESULTS: QMiX and 1% NaOCl killed all planktonic E. faecalis and plaque
      bacteria in 5 s, while 2% CHX and MTAD were unable to kill all plaque bacteria in
      30 s, and some E. faecalis cells survived even 3 min of exposure. QMiX and 2%
      NaOCl killed up to 12 times more biofilm bacteria than 1% NaOCl (P < 0.01), 2%
      CHX (P < 0.05; P < 0.001) and MTAD (P < 0.05; P < 0.001). QMiX removed smear
      layer equally well as EDTA (P = 0.18 * 10(-5)). CONCLUSION: QMiX and NaOCl were
      superior to CHX and MTAD under laboratory conditions in killing E. faecalis and
      plaque bacteria in planktonic and biofilm culture. Ability to remove smear layer
      by QMiX was comparable to EDTA.

PMID- 23134159
TI  - Geographic distance, contact and family perceptions of quality nursing home care.

PMID- 23134160
TI  - Cannot ventilate--paralyze!

PMID- 23134161
TI  - The difficult airway trolley in pediatric anesthesia: an international survey of
      experience and training.
AB  - BACKGROUND: The pediatric difficult airway can be unexpected, leading to
      significant morbidity and mortality. Standardized emergency airway equipment
      should be available on a regularly checked difficult airway trolley (DAT). We
      conducted a survey to investigate pediatric anesthetists' knowledge, experience,
      and confidence with the DAT. METHODS: Members of the Association of Paediatric
      Anaesthetists of Great Britain and Ireland (APAGBI), European Society for
      Paediatric Anaesthesiology (ESPA) and their national societies, Canadian
      Pediatric Anesthesia Society (CPAS), and Society for Paediatric Anaesthesia in
      New Zealand and Australia (SPANZA) were invited to complete a survey between
      January and April 2011. RESULTS: Six hundred and ninety-three anesthetists
      replied to the questionnaire. Six hundred and thirty-three (92%) stated they have
      a DAT in their theater suite, with 587 (98%) knowing its location. Three hundred
      and eight-seven (56%) anesthetists received formal DAT training. The lowest
      training levels were observed in Australia and the UK; 42% and 59%, respectively.
      Those receiving training were more likely to be confident/very confident in
      knowing the DAT contents (r = -0.321, P = 0.01). Three hundred and fifty-five
      (59%) anesthetists had used the DAT in the last 6 months, 82 (14%) in the last 6
      12 months, 91 (15%) >1 year ago, and 72 (12%) had never used it. Frequency of use
      correlated moderately with higher confidence levels (r = -0.398, P = 0.01). One
      hundred and eight-three (31%) reported having experienced problems with DAT
      equipment (missing 20%, faulty 4%, unfamiliarity 7%). DISCUSSION: Training and
      recent use of the DAT increases anesthetists' confidence, but is not a universal
      practice. A significant number of anesthetists reported problems with the DAT,
      raising issues of equipment maintenance and quality control.

PMID- 23134162
TI  - Emergency airway access in children--transtracheal cannulas and tracheotomy
      assessed in a porcine model.
AB  - OBJECTIVES: In the rare scenario when it is impossible to oxygenate or intubate a
      child, no evidence exists on what strategy to follow. AIM: The aim of this study
      was to compare the time and success rate when using two different transtracheal
      needle techniques and also to measure the success rate and time when performing
      an emergency tracheotomy in a piglet cadaver model. METHODS: In this randomized
      cross-over study, we included 32 anesthesiologists who each inserted two
      transtracheal cannulas (TTC) using a jet ventilation catheter and an intravenous
      catheter in a piglet model. Second, they performed an emergency tracheotomy. A
      maximum of 2 and 4 min were allowed for the procedures, respectively. The TTC
      procedures were recorded using a video scope. RESULTS: Placement of a
      transtracheal cannula was successful in 65.6% and 68.8% of the attempts (P =
      0.76), and the median duration of the attempts was 69 and 42 s (P = 0.32), using
      the jet ventilation catheter and the intravenous catheter, respectively.
      Complications were frequent in both groups, especially perforation of the
      posterior tracheal wall. Performing an emergency tracheotomy was successful in
      97%, in a median of 88 s. CONCLUSIONS: In a piglet model, we found no significant
      difference in success rates or time to insert a jet ventilation cannula or an
      intravenous catheter transtracheally, but the incidence of complications was
      high. In the same model, we found a 97% success rate for performing an emergency
      tracheotomy within 4 min with a low rate of complications.

PMID- 23134163
TI  - Early pediatric cardiac anesthesia in Toronto.

PMID- 23134164
TI  - Topical anesthesia for laser treatment of retinopathy of prematurity.

PMID- 23134165
TI  - Postoperative analgesia and infant vitreoretinal surgery.

PMID- 23134166
TI  - Spontaneous ventilation via facemask and laryngeal mask airway as bridge to
      extracorporeal membrane oxygenation during long-segment tracheal stenosis repair.

PMID- 23134167
TI  - A novel use for the Glidescope (r) in pediatric anesthesia.

PMID- 23134168
TI  - Successful airway management in patient with Goldenhar's syndrome using Truview
      PCD (r) laryngoscope.

PMID- 23134173
TI  - A sequential Pd/norbornene-catalyzed process generates o-biaryl carbaldehydes or
      ketones via a redox reaction or 6H-dibenzopyrans by C-O ring closure.
AB  - o-Biaryl carbaldeydes and ketones are obtained through the one-pot reaction of o
      aryl iodides with o-bromobenzyl alcohols under the catalytic action of Pd and
      norbornene, in the presence of a base. The same reaction can also give
      dibenzopyrans by Pd and norbornene catalysis with a different termination,
      leading to C-O ring closure. In both cases the process first leads to a five
      membered palladacycle, which controls C-C coupling, then to a seven-membered
      oxapalladacycle, which gives aldehydes and ketones or dibenzopyrans.

PMID- 23134175
TI  - Novel conformation of an RNA structural switch.
AB  - The RNA duplex, (5'GACGAGUGUCA)(2), has two conformations in equilibrium. The
      nuclear magnetic resonance solution structure reveals that the major conformation
      of the loop, 5'GAGU/3'UGAG, is novel and contains two unusual Watson
      Crick/Hoogsteen GG pairs with G residues in the syn conformation, two A residues
      stacked on each other in the center of the helix with inverted sugars, and two
      bulged-out U residues. The structure provides a benchmark for testing approaches
      for predicting local RNA structure and a sequence that allows the design of a
      unique arrangement of functional groups and/or a conformational switch into
      nucleic acids.

PMID- 23134178
TI  - Flow-mediated K(+) secretion in horses intoxicated with lolitrem B (perennial
      ryegrass staggers).
AB  - AIM: To investigate the effects of lolitrem B intoxication on renal K(+)
      secretion in response to increased tubular flow rates. METHODS: Results are
      derived from a repeated measure pilot study of seven horses fed non-perennial
      ryegrass feed for a week prior to exposing them to perennial ryegrass seed and
      hay that contained an average of 2 ppm lolitrem B. At the end of the control and
      treatment period frusemide (1 mg/kg I/V) was administered and serial fractional
      excretion of K(+)(FEK(+)) and fractional excretion of Na(+)(FENa(+)) calculated.
      Baseline concentration of aldosterone in plasma, serum K(+)concentration and feed
      K(+) concentration were also compared. RESULTS: Key findings included a reduced
      change in FEK(+) from 0 to 15 minutes in response to frusemide administration
      (p=0.022, Wilcoxon signed-rank test) and a reduced baseline concentration of
      aldosterone in plasma (p=0.022, Wilcoxon signed-rank test) during the treatment
      period compared with the control. CONCLUSIONS: Results suggest that lolitrem B
      intoxication reduced flow-mediated K(+) secretion and interfered with aldosterone
      production or secretion. However, further investigation is required to validate
      these findings and to further elucidate the underlying pathophysiology. CLINICAL
      RELEVANCE: Lolitrem B intoxication in horses may cause disruption to electrolyte
      handling in addition to neurological deficits.

PMID- 23134179
TI  - Preliminary experience with CT-guided high-dose rate brachytherapy as an
      alternative treatment for hepatic recurrence of cholangiocarcinoma.
AB  - BACKGROUND: Intrahepatic recurrence after resection of intrahepatic or hilar
      cholangiocarcinoma represents a main reason for the poor prognosis of bile duct
      cancer. As no standard treatment has been established so far, the aim of this
      study was to analyse the safety and efficacy of computed tomography-guided high
      dose rate brachytherapy (CT-HDRBT) as an alternative treatment in those patients.
      METHODS: The outcomes of 10 patients, who had been treated at least once for
      recurrent cholangiocarcinoma by CT-HDRBT, were retrospectively analysed. RESULTS:
      The median survival of all patients after primary liver resection was 85 months
      [95% confidence interval (CI) 68.129-101.871] with overall 1- and 5-year survival
      rates of 100% and 78.7%, respectively. After the occurrence of intrahepatic
      tumour recurrence, a total of 15 CT-HDRBT procedures were performed, alone or
      combined with other recurrence treatments, without any major complications
      according to the Society of Interventional Radiology classification. The 1-year
      and 5-year survival rates after recurrence treatment were 77.1% and 51.4%,
      respectively. CONCLUSIONS: CT-HDRBT represents a safe treatment option for
      patients with recurrent bile duct cancer. As a part of a multimodal concept, CT
      HDRBT might lead to a prolongation of survival in selected patients but further
      studies are urgently needed to prove this concept.

PMID- 23134180
TI  - Pancreatoenteral anastomosis or direct closure of the pancreatic remnant after a
      distal pancreatectomy: a single-centre experience.
AB  - BACKGROUND: A major complication of a distal pancreatectomy (DP) is the formation
      of a post-operative pancreatic fistula (POPF). In spite of the utilization of
      numerous surgical techniques no consensus on an appropriate technique for closure
      of the pancreatic remnant after DP has been established yet. The aim of this
      study was to analyse the impact of pancreatoenteral anastomosis (PE) vs. direct
      closure (DC) of the pancreatic remnant on POPF. METHODS: A total of 198
      consecutive patients who underwent a distal pancreatectomy between 2002 and 2010
      at our institution were retrospectively analysed for post-operative morbidity and
      mortality. RESULTS: One hundred and fifty-one patients (76.3%) received DC
      whereas PE was performed in 47 patients (23.7%). The incidence of POPF was higher
      in the DC group (22% vs. 11%), whereas the rate of post-operative haemorrhage was
      higher in the PE group (11% vs. 7%). However, these differences were not
      significant. Additionally, there were no significant differences in overall post
      operative morbidity and mortality between the groups. CONCLUSIONS: The
      performance of PE instead of DC may be considered as a safe alternative in
      individual patients, but it does not significantly lead to a general improvement
      in post-operative outcome after DP. An interdisciplinary collaboration in the
      prevention and treatment of POPF therefore remains essential.

PMID- 23134181
TI  - Role of radical surgery in patients with stage IV gallbladder cancer.
AB  - OBJECTIVES: The role of surgery in stage IV gallbladder (GB) cancer is not well
      established. This study analyses prognostic factors in patients with stage IV GB
      cancer following surgical resection with the aim of identifying a subgroup of
      patients who might benefit from surgical resection. METHODS: Clinicopathological
      details were analysed for 94 patients who were surgically treated for stage IV GB
      cancer at Seoul National University Hospital. RESULTS: Median survival was 8
      months in patients with either stage IVa or IVb disease. Sixteen patients (17.0%)
      underwent resection with curative intent, which increased overall survival over
      that in patients undergoing palliative surgery (P < 0.001). No survival benefit
      was seen following surgery with curative intent in patients with stage IVa
      disease (P = 0.764). Surgery with curative intent resulted in a survival benefit
      in patients with stage IVb disease, patients with an isolated liver metastasis
      near the GB bed (median survival: 31 months vs. 9 months; P < 0.001) and patients
      with limited numbers of peritoneal implantations (median survival: 20 months vs.
      6 months; P = 0.002). Preoperative serum carcinoembryonic antigen (CEA) (P =
      0.018), surgery with curative intent (P = 0.045) and adjuvant chemotherapy (P =
      0.002) were independent prognostic factors in patients with stage IV GB cancer.
      CONCLUSIONS: Surgery in combination with systemic chemotherapy may be beneficial
      in carefully selected patients with stage IVb GB cancer.

PMID- 23134182
TI  - The role of interventional radiology in the management of surgical complications
      after pancreatoduodenectomy.
AB  - OBJECTIVES: This study evaluates the role of interventional radiology (IR) in the
      management of postoperative complications after pancreatoduodenectomy (PD).
      METHODS: A total of 120 consecutive patients were reviewed to identify IR
      procedures performed for early complications after PD. RESULTS: Findings showed
      that 24 patients (20.0%) required urgent radiological or surgical re-intervention
      for early complications, including 11 instances of post-pancreatectomy
      haemorrhage (PPH), six intra-abdominal abscesses, two bile leaks, one pancreatic
      fistula and one bowel ischaemia. Three of 24 complications were managed by
      surgery and 21 were managed by IR. Two of 11 PPHs involved intraluminal
      haemorrhage (ILH) and nine involved intra-abdominal haemorrhage (IAH). One ILH
      was managed conservatively and one required surgical intervention. In eight of
      nine patients with IAH, the bleeding site was identified on computed tomography
      angiography, and endovascular stenting or coil embolization were performed. No
      patient required a re-look laparotomy following IR for haemorrhage or intra
      abdominal abscess. Overall, three of 120 patients required an urgent re-look
      laparotomy for early complications. CONCLUSIONS: Rates of major morbidity after
      PD remain high. However, many significant complications (PPH, pancreatic fistula,
      intra-abdominal abscess) can be managed by IR, reducing the need for reoperation.
      Re-look surgery is still required in a small percentage (2.5%) of patients.

PMID- 23134183
TI  - A survey in the hepatopancreatobiliary community on ways to enhance patient
      recovery.
AB  - OBJECTIVES: Both laparoscopic techniques and multimodal enhanced recovery
      programmes have been shown to improve recovery and reduce length of hospital
      stay. Interestingly, evidence-based care programmes are not widely implemented,
      whereas new, minimally invasive surgical procedures are often adopted with very
      little evidence to support their effectiveness. The present survey aimed to shed
      light on experiences of the adoption of both methods of optimizing recovery.
      METHODS: An international, web-based, 18-question, electronic survey was composed
      in 2010. The survey was sent out to 673 hepatopancreatobiliary (HPB) centres
      worldwide in June 2010 to investigate international experiences with laparoscopic
      liver surgery, fast-track recovery programmes and surgery-related equipoise in
      open and laparoscopic techniques and to assess opinions on strategies for
      adopting laparoscopic liver surgery in HPB surgical practice. RESULTS: A total of
      507 centres responded (response rate: 75.3%), 161 of which finished the survey
      completely. All units reported performing open liver resections, 24.2% performed
      open living donor resections, 39.1% carried out orthotopic liver
      transplantations, 87.6% had experience with laparoscopic resections and 2.5%
      performed laparoscopic living donor resections. A median of 50 (range: 2-560)
      open and 9.5 (range: 1-80) laparoscopic liver resections per surgical unit were
      performed in 2009. Patients stayed in hospital for a median of 7 days (range: 2
      15 days) after uncomplicated open liver resection and a median of 4 days (range:
      1-10 days) after uncomplicated laparoscopic liver resection. Only 28.0% of
      centres reported having experience with fast-track programmes in liver surgery.
      The majority considered the instigation of a randomized controlled trial or a
      prospective register comparing the outcomes of open and laparoscopic techniques
      to be necessary. CONCLUSIONS: Worldwide dissemination of laparoscopic liver
      resection is substantial, although laparoscopic volumes are low in the majority
      of HPB centres. The adoption of enhanced recovery programmes in liver surgery is
      limited and should be given greater attention.

PMID- 23134184
TI  - Comparison of liver parenchymal ablation and tissue necrosis in a cadaveric
      bovine model using the Harmonic Scalpel, the LigaSure, the Cavitron Ultrasonic
      Surgical Aspirator and the Aquamantys devices.
AB  - OBJECTIVES: The amount of tissue that is ablated or necrosed at the line of
      parenchymal transection is of clinical significance in the interpretation of
      resection margin status following hepatic resection. The aim of this study was to
      define the extent of parenchymal ablation and necrosis in liver tissue using the
      Harmonic Scalpel, the LigaSure, the Cavitron Ultrasonic Surgical Aspirator (CUSA)
      and the Aquamantys dissector ex vivo. METHODS: Mounted blocks of non-perfused
      bovine liver were transected using the Harmonic Scalpel, LigaSure, CUSA and
      Aquamantys devices. Outcome measures included parenchymal ablation (ablation band
      widths and weights) and tissue necrosis band widths along the line of
      transection. Each experiment was replicated five times. RESULTS: All devices were
      associated with parenchymal ablation (Harmonic Scalpel, 4.73 +/- 1.62 mm;
      LigaSure, 4.55 +/- 2.02 mm; CUSA, 7.16 +/- 2.87 mm; Aquamantys, 4.75 +/- 1.43 mm)
      and tissue necrosis (Harmonic Scalpel, 1.07 +/- 0.46 mm; LigaSure, 1.36 +/- 0.36
      mm; CUSA, 0.81 +/- 0.21 mm; Aquamantys, 0.81 +/- 0.36 mm). CONCLUSIONS: The
      Harmonic Scalpel, LigaSure, CUSA and Aquamantys devices were associated with
      bands of tissue loss along the hepatic parenchymal transection line in this
      benchtop cadaveric model. This should be taken into account in the interpretation
      of resection margin status following liver resection.

PMID- 23134185
TI  - Surgical treatment of gastrinomas: a single-centre experience.
AB  - BACKGROUND: Gastrinomas are rare neuroendocrine tumours, and responsible for
      Zollinger-Ellison syndrome (ZES). Surgery is the only treatment that can cure
      gastrinomas. The success of surgical treatment of gastrinomas in a single centre
      was evaluated. METHODS: A retrospective review of all patients who underwent
      resection for a gastrinoma between 1992 and 2011 at a single institution was
      performed. Presentation, diagnostics, operative management and outcome were
      analysed. RESULTS: Eleven patients with a median age of 46 years were included.
      All patients had fasting hypergastrinaemia and a primary tumour was localized
      using imaging studies in all patients. A pylorus-preserving
      pancreaticoduodenectomy was performed in three patients: two patients underwent
      duodenectomy and one patient central pancreatectomy. The remaining five patients
      underwent enucleation. A primary tumour was removed in nine patients: five
      tumours were situated in the pancreas, three in the duodenum and one patient was
      considered to have a primary lymph node gastrinoma. The median follow-up was 3
      years (range 1-15) after which 7 patients were disease-free and 3 patients had
      (suspected) metastatic disease. One patient died 13 years after initial surgery.
      CONCLUSION: The success of surgical treatment of a gastrinoma in this series was
      7/11 with a median follow-up of 3 years; comparable to recent published studies.

PMID- 23134186
TI  - Carrier-bound fibrin sealant compared to oxidized cellulose application after
      liver resection.
AB  - OBJECTIVE: The aim of the study was to compare the incidence of post-operative
      complications between those patients that received TachoSil to the transection
      surface of the liver vs. those that received Surgicel. METHODS: Retrospective
      study of a prospective database in a tertiary hospital. Primary endpoints were
      overall complications. Secondary endpoints were liver surgery-specific composite
      endpoint, major complications and hospital stay. Uni- and multivariate analysis
      of predictive factors for complications and subgroup analysis were performed.
      RESULTS: One hundred thirty-three liver resections were performed between 9
      November 2007 and 2 November 2011: 64 with TachoSil and 69 with Surgicel
      application. Both groups were equivalent concerning demographic, clinical and
      major intra-operative data. No significant differences were observed in overall
      complication rate (62.5% vs. 62.3%), liver surgery-specific composite endpoint
      (12.5% vs. 18.8%), major complication rate (18.7% vs. 24.6%) and median hospital
      stay (13 vs. 10 days) for TachoSil and Surgicel application, respectively.
      Predictive factors for complications in multivariate analysis were: American
      Society of Anesthesiology Score >=3 and duration of surgery >240 min. Subgroup
      analysis found a reduced complication rate with TachoSil for major hepatectomy.
      CONCLUSION: The results of the present study suggest that the routine use of
      TachoSil after a liver resection does not reduce the overall complication rate
      compared with Surgicel application. However, TachoSil may be beneficial in a
      major hepatectomy.

PMID- 23134187
TI  - Laparoscopic cholecystectomy is the preferred approach in cirrhosis: a
      nationwide, population-based study.
AB  - BACKGROUND/AIM: To assess the impact of open versus laparoscopic surgery in
      cirrhotic patients undergoing a cholecystectomy using the Nationwide Inpatient
      Sample (NIS). METHODS: All patients with cirrhosis who underwent a
      cholecystectomy (open or laparoscopic) between 2003 and 2006 were queried from
      the NIS. Associated complications including infection, transfusion, reoperation,
      liver failure and mortality were determined. RESULTS: A total of 3240 patients
      with cirrhosis underwent a cholecystectomy: 383 patients underwent an open
      cholecystectomy (OC) whereas 2857 patients underwent a laparoscopic
      cholecystectomy (LC), which included 412 patients converted (LCC) from a LC to an
      OC. Post-operative infection was higher in OC as opposed to a laparoscopic
      cholecystectomy (TLC) or LCC (3.5% versus 0.7% versus 0.2%, P < 0.0001). The need
      for a blood transfusion was significantly higher in the OC and LCC groups as
      compared with the TLC group (19.2% versus 14.4% versus 6.2%, P < 0.0001).
      Reoperation was more frequent after OC or LCC versus TLC (1.5% versus 2.5% versus
      0.8%, P = 0.007). In-hospital mortality was higher after OC as compared with TLC
      and LCC (8.3% versus 1.3% versus 1.4%, P < 0.0001). CONCLUSION: Patients with
      cirrhosis have increased in-hospital morbidity and mortality after an open as
      opposed to a laparoscopic or conversion to an open cholecystectomy. LC should be
      the preferred initial approach in cirrhotic patients.

PMID- 23134188
TI  - Does pharmacological conditioning with the volatile anaesthetic sevoflurane offer
      protection in liver surgery?
AB  - BACKGROUND: A recently published randomized control trial (RCT) showed a
      protection of the remnant liver from ischemia-reperfusion (I/R) injury by
      pharmacological pre-conditioning with a volatile anaesthetic in patients
      undergoing hepatic resection. Whether the continuous application of volatile
      anaesthetics (pharmacological conditioning) also protects against I/R injury is
      unknown. METHODS: Consecutive patients undergoing liver resection with inflow
      occlusion from 2005-2007 were included in the trial. Two groups of anaesthesia
      regimens with either continuous application of the volatile anaesthetic
      sevoflurane (pharmacological conditioning) or continuous infusion of the
      intravenous (i.v.) anaesthetic propofol (control group) were compared. Endpoints
      were serum-peak-aspartate aminotransferase (AST)/ alanine aminotranferease (ALT)
      levels, length of stay (LOS) and intensive care unit (ICU) stays, and the
      occurrence of post-operative complications. RESULTS: Two hundred and twenty-seven
      patients were included. Pharmacological conditioning did not protect the remnant
      liver from IR injury (adjusted difference for peak-AST:61.9 U/l, 95% confidence
      interval (CI): -151.7-275.4 U/l, P = 0.568; peak-ALT:136.1 U/l, 95% CI: -113.7
      385.9 U/l, P = 0.284) nor reduce LOS (adjusted difference 0.9 days, 95% CI: -2.6
      4.3 days, P = 0.622) or ICU stay (1.6 days, 95% CI: -0.2-3.3 days, P = 0.079),
      and was not associated with reduced complication rates (adjusted OR 1.12, 95%
      CI:0.6-2.3, P = 0.761) compared with the control group. CONCLUSION: In this
      retrospective study, continuous volatile anaesthesia in liver resection does not
      provide protection of the remnant liver from IR injury compared with continuous
      i.v. anaesthesia.

PMID- 23134189
TI  - Postoperative mortality and need for transitional care following liver resection
      for metastatic disease in elderly patients: a population-level analysis of 4026
      patients.
AB  - OBJECTIVES: The goal of this study was to characterize the association of age
      with postoperative mortality and need for transitional care following hepatectomy
      for liver metastases. METHODS: A retrospective cohort study using the Nationwide
      Inpatient Sample (2005-2008) was performed. Patients undergoing hepatectomy for
      liver metastases were categorized by age as: Young (aged <65 years); Old (aged 65
      74 years), and Oldest (aged >=75 years). Multivariate logistic regression
      analyses were performed to identify predictors of in-hospital mortality and need
      for transitional care (non-home discharge). RESULTS: A total of 4026 patients
      were identified; 36.6% (n = 1475) were elderly (aged >=65 years). Rates of in
      hospital mortality and non-home discharge increased with advancing age group
      [1.3% vs. 2.2% vs. 3.3% (P = 0.005) and 2.1% vs. 6.1% vs. 18.3% (P < 0.001),
      respectively]. Independent predictors of in-hospital mortality were age within
      the Oldest category [odds ratio (OR) 2.21, 95% confidence interval (CI) 1.19
      4.12] and a Deyo Comorbidity Index score of >=3 (OR 6.95, 95% CI 3.55-13.60).
      Independent predictors for need for transitional care were age within the Old
      group (OR 2.44, 95% CI 1.66-3.58), age within the Oldest group (OR 8.48, 95% CI
      5.87-12.24), a Deyo score of 1 (OR 2.00, 95% CI 1.40-2.85), a Deyo score of 2 (OR
      4.70, 95% CI 2.93-7.56), a Deyo score of >=3 (OR 6.41, 95% CI 3.67-11.20), and
      female gender (OR 1.56, 95% CI 1.15-2.11). CONCLUSIONS: Although increasing age
      was associated with higher risk for in-hospital mortality, the absolute risk was
      low and within accepted ranges, and comorbidity was the primary driver of
      mortality. Conversely, need for transitional care was significantly more common
      in elderly patients. Therefore, liver resection for metastases is safe in well
      selected elderly patients, although consideration should be made for potential
      transitional care needs.

PMID- 23134190
TI  - Successful management of a large air embolus during an extended right hepatectomy
      with an emergency cardiopulmonary bypass.
AB  - BACKGROUND: An air embolus is a recognized but rare complication of a partial
      hepatectomy. The aim of this report was to describe the diagnosis and management
      of a large paradoxical air embolus during hepatic resection. METHODS: Case
      report. RESULTS: A single patient report of a massive paradoxical air embolus
      during an extended right hepatectomy is described. The diagnosis was confirmed by
      trans-oesophageal echo (video provided). After failed conservative management an
      emergency cardiopulmonary bypass was instituted with a successful outcome.
      CONCLUSION: Surgeons and anaesthetists involved in hepatic surgery should be
      aware of signs, investigations and management of this life-threatening intra
      operative complication.

PMID- 23134191
TI  - Rapid improvement in liver volume induced by portal vein ligation and staged
      hepatectomy: the ALPPS procedure.

PMID- 23134192
TI  - Icariin stimulates the proliferation of rat Sertoli cells in an ERK1/2-dependent
      manner in vitro.
AB  - Icariin (ICA), a major constituent of flavonoids from the Chinese medical herb
      Epimedium brevicornum Maxim, is found to be protective for male reproductive
      ability, with the underlying mechanism largely unknown. Our study here
      investigated the effects of ICA on Sertoli cells, which act as nurse cells for
      the germ cells developing. Icariin was found to stimulate Sertoli cell
      proliferation in a dose-dependent manner. Further study revealed that Icariin
      induced an obvious phosphorylation of ERK in Sertoli cells. Inhibition of
      activation of ERK by the ERK inhibitor U0126 nearly blocked the Icariin-induced
      proliferation of Sertoli cells. Taken together, our results suggest that Icariin
      promotes the proliferation of Sertoli cells in vitro by activating the ERK1/2
      signal pathway, which might at least partially, explain the protective role of
      Icariin on male reproductive ability. 

PMID- 23134193
TI  - Efficacy of acamprosate for alcohol dependence in a family medicine setting in
      the United States: a randomized, double-blind, placebo-controlled study.
AB  - BACKGROUND: Acamprosate has been found to enhance rates of complete abstinence
      and to increase percent days abstinent (PDA) from alcohol relative to placebo
      treatment. As most U.S. clinical trials of acamprosate have been conducted in
      alcohol and other drug specialty clinics, there is a need to examine the efficacy
      of acamprosate in generalist settings. This study tested the efficacy of
      acamprosate versus placebo on the primary study outcome of PDA in the treatment
      of alcohol-dependent patients in a family medicine setting. Secondary study
      outcomes included percent heavy drinking days (%HDD) and gamma
      glutamyltransferase level (normal or high). METHODS: A randomized, double-blind,
      placebo-controlled, parallel group design of acamprosate was conducted in 2
      family medicine settings (North Carolina and Wisconsin). One hundred volunteers
      were recruited primarily by advertisement, and participants were assigned to 666
      mg (2 pills) oral acamprosate 3 times daily (1,998 mg/d) or matching placebo over
      a 12-week period. All participants concomitantly received 5 sessions of a brief
      behavioral intervention from a family/primary care physician. RESULTS: No
      significant treatment effect of acamprosate was found on PDA or the secondary
      outcomes. Significant treatment goal by time interaction effects was found on PDA
      and %HDD. Participants who had an initial goal of abstinence versus a reduction
      in alcohol use improved on average over time in PDA and had less %HDD from
      baseline to the end of treatment. CONCLUSIONS: This clinical trial did not find
      evidence of efficacy for acamprosate compared to placebo among alcohol-dependent
      individuals recruited primarily by advertisement as studied in a primary care
      setting. Drinking outcomes significantly improved regardless of medication
      condition. A goal of abstinence was significantly associated with improved
      drinking outcomes, suggesting that alcohol-dependent patients with such a goal
      may do particularly well with counseling in a family medicine setting.

PMID- 23134194
TI  - Upsampling to 400-ms resolution for assessing effective connectivity in
      functional magnetic resonance imaging data with Granger causality.
AB  - Granger causality analysis of functional magnetic resonance imaging (fMRI) blood
      oxygen-level-dependent signal data allows one to infer the direction and
      magnitude of influence that brain regions exert on one another. We employed a
      method for upsampling the time resolution of fMRI data that does not require
      additional interpolation beyond the interpolation that is regularly used for
      slice-timing correction. The mathematics for this new method are provided, and
      simulations demonstrate its viability. Using fMRI, 17 snake phobics and 19
      healthy controls viewed snake, disgust, and neutral fish video clips preceded by
      anticipatory cues. Multivariate Granger causality models at the native 2-sec
      resolution and at the upsampled 400-ms resolution assessed directional
      associations of fMRI data among 13 anatomical regions of interest identified in
      prior research on anxiety and emotion. Superior sensitivity was observed for the
      400-ms model, both for connectivity within each group and for group differences
      in connectivity. Context-dependent analyses for the 400-ms multivariate Granger
      causality model revealed the specific trial types showing group differences in
      connectivity. This is the first demonstration of effective connectivity of fMRI
      data using a method for achieving 400-ms resolution without sacrificing accuracy
      available at 2-sec resolution.

PMID- 23134195
TI  - The Gottingen minipig(r) as an alternative non-rodent species for immunogenicity
      testing: a demonstrator study using the IL-1 receptor antagonist anakinra.
AB  - The use of recombinant human proteins for the treatment of several diseases has
      increased considerably during the last decades. A major safety and efficacy issue
      of biopharmaceuticals is their potential immunogenicity. To prevent
      immunogenicity, biotechnology-derived proteins are engineered to be as human-like
      as possible. Immunogenicity is mainly determined in non-human primates (NHP), as
      they are considered to be the best predictive animal species for human safety,
      based on their close relatedness to man. As minipigs are increasingly used in the
      safety evaluation of (bio)pharmaceuticals, the predictive value of the minipig in
      immunogenicity testing was evaluated in this study, using anakinra as a model
      compound. Animals were treated subcutaneously with either placebo, low- (0.5
      mg/kg), or high-dose (5 mg/kg) anakinra daily on 29 consecutive days. After the
      first and last dose, the pharmacokinetic (PK) profile of anakinra was evaluated.
      Antibodies directed to anakinra were measured on several time points during the
      treatment period. Furthermore, hematology, clinical chemistry, body weight,
      clinical signs, and histopathology of several organs were evaluated. No signs of
      toxicity were observed upon treatment with anakinra. PK parameters were
      comparable with those found in human and NHP studies performed with anakinra. All
      animals developed anti-anakinra antibodies. The results obtained in minipigs were
      comparable to those observed in monkeys. For anakinra, the predictive value of
      the minipig for immunogenicity testing was found to be comparable to that seen in
      NHP. However, more studies evaluating additional biopharmaceutical products are
      needed to support the use of the minipig as an alternative model for
      (immuno)toxicity testing, including immunogenicity.

PMID- 23134196
TI  - Effects of 12 weeks of block periodization on performance and performance indices
      in well-trained cyclists.
AB  - The purpose of this study was to compare the effects of two different methods of
      organizing endurance training in trained cyclists during a 12-week preparation
      period. One group of cyclists performed block periodization (BP; n = 8), wherein
      every fourth week constituted five sessions of high-intensity aerobic training
      (HIT), followed by 3 weeks of one HIT session. Another group performed a more
      traditional organization (TRAD; n = 7), with 12 weeks of two weekly HIT sessions.
      The HIT was interspersed with low-intensity training (LIT) so that similar total
      volumes of both HIT and LIT were performed in the two groups. BP achieved a
      larger relative improvement in VO2max than TRAD (8.8 +/- 5.9% vs 3.7 +/- 2.9%,
      respectively, < 0.05) and a tendency toward larger increase in power output at 2
      mmol/L [la(-)] (22 +/- 14% vs 10 +/- 7%, respectively, P = 0.054). Mean effect
      size (ES) of the relative improvement in VO2max , power output at 2 mmol/L [la(
      )], hemoglobin mass, and mean power output during 40-min all-out trial revealed
      moderate superior effects of BP compared with TRAD training (ES range was 0.62
      1.12). The present study suggests that BP of endurance training has superior
      effects on several endurance and performance indices compared with TRAD.

PMID- 23134197
TI  - Caregivers' attitudes regarding oral health in a long-term care institution in
      Brazil.
AB  - BACKGROUND AND OBJECTIVE: The number of elderly living in long-term care (LTC)
      institutions has been increasing in many countries. The objective of this study
      was to evaluate the caregivers' attitudes and considerations regarding oral
      health and oral health practices in an LTC institution in Porto Alegre, Brazil.
      MATERIALS AND METHODS: The population comprised the caregivers (n = 27) at an LTC
      in Porto Alegre, Brazil. Participants answered a questionnaire assessing the time
      of work at the LTC, number of elderly under their responsibility, their previous
      training to perform general and oral healthcare, availability of oral hygiene
      supplies and oral hygiene tasks they performed. RESULTS: A total of eighteen
      (75%) and 23 (95.8%) of the caregivers answered they performed teeth and denture
      brushing as part of their routine. When asked about performing hygiene of the
      mucosa with gauze, 21 (87.5%) participants stated that they did so. However, when
      asked if they would motivate the independent elderly to perform oral hygiene,
      only 10 (41.7%) of the caregivers responded positively. CONCLUSION: Caregivers'
      oral health practices are in accordance with good oral health methods and are not
      associated with difficulties in performing oral hygiene. However, the high number
      of elderly people in their care could possibly overwhelm caregivers' practices.
      Future qualitative assessment of these issues is needed.

PMID- 23134198
TI  - Potential role of phospholipids in determining the internal tissue distribution
      of perfluoroalkyl acids in biota.

PMID- 23134199
TI  - Personality types and specialist choices in medical students.
AB  - BACKGROUND: Research on the correlation between personality and students'
      specialty choice is helpful in their career counselling process and in predicting
      the future distribution of the specialties in a country. AIMS: This study is the
      first of its kind in the Arab world. The research questions were: (1) What is the
      influence of gender on the personality profiles of medical students? (2) What are
      the personality profiles of students categorized according to their preferred
      specialist choices? (3) What are the preferred career choices of students
      categorized according to the stage of their medical education? METHOD: A cross
      sectional study was performed at King Khalid University Medical School including
      590 students during the academic year 2010-2011. A long version of the Zuckerman
      Kuhlman personality questionnaire measuring five personality factors was used.
      Students were also asked for their specialty interests. Students were asked by
      means of a written questionnaire. RESULTS: Study response was 92.5%. Surgery was
      the single most popular specialty amongst both male and female students. Males
      had significantly higher scores on the 'impulsive sensation seeking' scale and
      students preferring a surgery specialty had the highest score on the 'impulsive
      sensation seeking', 'neuroticism-anxiety', 'aggression-hostility' and
      'sociability' scales. Hospital-based, surgical and primary care specialties
      became more popular as students progressed through their undergraduate years.
      CONCLUSIONS: Different personality types have distinct preferences in medical
      students' choice of careers. Personality and specialty choice research can
      enhance career counselling of medical students and fresh graduates. This also has
      implications for predicting the specialty distribution of the future health
      careers.

PMID- 23134202
TI  - Haemoglobin variability in the early post-transplant period: association with
      graft survival and mortality.
AB  - AIM: Haemoglobin (Hb) variability is associated with poor survival in patients
      with chronic kidney disease. Association of Hb variability after kidney
      transplantation with patients' and graft survival has not been adequetly studied.
      METHODS: This retrospective study used registry data to examine the association
      between Hb variability in the early post-transplant period (first 6 months) and
      graft survival after kidney transplantatin. Kaplan-Meier and Cox regression
      analyses were used for univariate and multivariate associations between
      mortality, death censored graft survival and the composite outcome of both, in
      752 patients after kidney transplantation. Hb values were collected each month
      during the first 6 months after transplantation, and Hb variavility was
      calculated using the residual standard deviation method. RESULTS: The highest
      quartile of Hb variability was associated with inferior graft and patients'
      survival in univariate (hazard ratio (HR) 2.18; 95% confidence interval (CI) 1.51
      to 3.13; P < 0.001) and multivariate models (HR 1.5; 95% CI 1.029 to 2.18; P =
      0.035). This association was mainly due to increased death censored graft failure
      in the high variability group (HR 2.75; 95% CI 1.73 to 4.38; P < 0.001) and (HR
      1.67; 95% CI 1.023 to 2.74; P = 0.04) in the univariate and multivariate models,
      respectively. There was no association between Hb variability and the risk of
      death (HR 1.51; 95% CI 0.88 to 2.57; P = 0.132). CONCLUSION: High Hb variability
      is independently associated with inferior graft survival in patients after kidney
      transplantation.

PMID- 23134201
TI  - Xanthogranulomatous cholecystitis: a clinicopathological study of its association
      with gallbladder carcinoma.
AB  - OBJECTIVES: To determine the distribution of macrophages (MPhi) in both
      xanthogranulomatous cholecystitis (XGC) and gallbladder carcinoma (GBC) and to
      analyze the association between XGC and GBC. METHODS: From January 2009 to June
      2011, 110 patients with gallbladder diseases, including 35 with GBC, 45 with XGC
      and 30 with chronic cholecystitis (CC), were enrolled. Immunohistochemistry stain
      and real-time polymerase chain reaction using oncogenes (BCL-2, c-Myc) and anti
      oncogene genes (p53, p21) were performed, serum expressions of tumor marker (CA19
      9, CA724 and CA242) were also conducted. MPhi were used to determine their
      potential role in the carcinogenesis of GBC. RESULTS: BCL-2 and c-Myc expressions
      gradually increased among CC, XGC and GBC (P = 0.032 and P = 0.020,
      respectively); while p53 and p21 were similar in the three groups (P = 0.167 and
      P = 0.122, respectively). Serum BCL-2 and c-Myc were significantly correlated
      with their tissue levels; in terms of serum tumor markers, which gradually
      increased among CC, XGC and GBC, however, CA242 and CA724 were both negative in
      XGC but positive in GBC. Furthermore, gradually increasing MPhi counts were
      observed among CC, XGC and GBC groups; c-Myc and CA724 were independent
      predictors for the differentiation of XGC and GBC. CONCLUSIONS: XGC is an
      uncommon inflammatory condition distinct from CC and may be associated with the
      precancerous nature of GBC for its upregulated oncogenes and MPhi biology. c-Myc
      and CA724 were independent predictors for the differentiation of XGC and GBC.

PMID- 23134203
TI  - In vitro anti-influenza activity of a protein-enriched fraction from larvae of
      the housefly (Musca domestica).
AB  - CONTEXT: Insects are a large, unexplored and unexploited source of potentially
      useful compounds for modern medicine. The larvae of the housefly (Musca
      domestica) have been used to study immune-induced molecules because they can
      survive in pathogenic environments. OBJECTIVE: The antiviral activity of a
      protein-enriched fraction (PEF) from the larvae of the housefly was evaluated in
      vitro and the possible antiviral mechanism was studied. MATERIALS AND METHODS:
      PEF was isolated from the larvae of the housefly. The cytotoxicity of PEF was
      detected by the MTT assay. The in vitro antiviral activity of PEF against
      influenza virus was investigated. PEF was incubated with the virus and its target
      cells under various conditions, and its antiviral effects were examined by
      reduction in virus yield in cell cultures. Experiments with ribavirin were
      performed in parallel under the same conditions. RESULTS: The results indicated
      that PEF had minimal cytotoxicity against MDCK cells and the CC50 value was
      calculated to be 284.45 MUg/ml. The antiviral results showed the loss of
      infectious capacity was more than two log (2) units in cell cultures compared
      with virus control. The effect of PEF was direct virucidal activity and the
      interference on the adsorption of cell and virus. The antiviral mechanism of PEF
      is different from ribavirin. CONCLUSION: The results indicate that PEF showed
      strong antiviral activity against influenza virus at a very early stage of the
      interaction with virus particles or their entry into the cells. PEF has a great
      potential as a resource of healthy products.

PMID- 23134204
TI  - Identification of the dimer interface of a bacterial Ca(2+)/H(+) antiporter.
AB  - Members of the calcium/cation antiporter superfamily, including the cardiac
      sodium/calcium exchangers, are secondary active transporters that play an
      essential role in cellular Ca(2+) homeostasis. A notable feature of this group of
      transporters is the high levels of sequence similarity in relatively short
      sequences constituting the functionally important alpha-1 and alpha-2 regions in
      contrast to relatively lower degrees of similarity in the extended adjoining
      sequences. This suggests a similar structure and function of core transport
      machinery but possible differences in topology and/or oligomerization, a topic
      that has not been adequately addressed. Here we present the first example of
      purification of a bacterial member of this superfamily (CAX(CK31)) and analyze
      its quaternary structure. Purification of CAX(CK31) required the presence of a
      choline headgroup-containing detergent or lipid to yield stable preparations of
      the monomeric transporter. H(+)-driven Ca(2+) transport was demonstrated by
      reconstituting purified CAX(CK31) into liposomes. Dimeric CAX(CK31) could be
      isolated by manipulation of detergent micelles. Dimer formation was shown to be
      dependent on micelle composition as well as protein concentration. Furthermore,
      we establish that CAX(CK31) forms dimers in the membrane by analysis of cross
      linked proteins. Using a dimeric homology model derived from the monomeric
      structure of the archaeal NCX homologue (Protein Data Bank entry  3V5U ), we
      introduced cysteine residues and through cross-linking experiments established
      the role of transmembrane helices 2 and 6 in the putative dimer interface.

PMID- 23134205
TI  - The lunule of caligid copepods: an evolutionarily novel structure.
AB  - Nearly half of the genera of the family Caligidae possess an evolutionarily novel
      structure called the "lunule" on the ventral surface of the frontal plate.
      Lunules are paired cup-like suckers that assist in securing attachment of the
      copepod parasite to its host. Although present in genera such as Caligus and
      Pseudocaligus, lunules are absent in other caligid genera such as Lepeophtheirus
      as well as in more primitive caligiforms such as members of the families
      Trebiidae and Dissonidae. We compared the morphology and development of the
      anterior margin of the frontal plates between two caligids, Pseudocaligus fugu
      and Lepeophtheirus sekii, and a more basal caligiform, Dissonus heronensis (a
      dissonid), using scanning electron, transmission electron, and laser confocal
      microscopes. Our observations suggest that the lunules originated as a
      modification of the marginal membranes of the ancestral frontal plates. We also
      demonstrated the presence of an anlagen cell population for the lunule and
      marginal membrane in the developing frontal plate. These primordial cells can be
      detected as early as the first stage of the chalimus phase. Based on these
      observations, an evolutionary scenario for the lunule is proposed based on
      cytological evidence. This case study enhances our understanding of "evolutionary
      novelty," which is a main focus of contemporary evolutionary developmental
      biology.

PMID- 23134206
TI  - Many ways to make a novel structure: a new mode of sex comb development in
      Drosophilidae.
AB  - On macroevolutionary time scales, the same genes can regulate the development of
      homologous structures through strikingly different cellular processes. Comparing
      the development of similar morphological traits in closely related species may
      help elucidate the evolutionary dissociation between pattern formation and
      morphogenesis. We address this question by focusing on the interspecific
      differences in sex comb development in Drosophilids. The sex comb is a recently
      evolved, male-specific structure composed of modified bristles. Previous work in
      the obscura and melanogaster species groups (Old World Sophophora) has identified
      two distinct cellular mechanisms that give rise to nearly identical adult
      morphologies. Here, we describe sex comb development in a species from a more
      distantly related lineage, the genus Lordiphosa. Although the expression of key
      regulatory genes is largely conserved in both clades, the cell behaviors
      responsible for sex comb formation show major differences between Old World
      Sophophora and Lordiphosa. We suggest that the many-to-one mapping between
      development and adult phenotype increases the potential for evolutionary
      innovations.

PMID- 23134207
TI  - Early cleavage in Phoronis muelleri (Phoronida) displays spiral features.
AB  - The view that early cleavage in Phoronida follows a radial pattern is widely
      accepted. However, data supporting this characterization are ambiguous. Studies
      have been repeatedly reporting variation between individual embryos, and the
      occurrence of embryos exhibiting oblique divisions or nonradial cell
      arrangements. Such embryos were often considered to represent variation within
      radial cleavage, or artificial appearances. Cleavage in Phoronis muelleri was
      previously characterized as "derived radial," but also oblique spindles and cell
      elongations, and shifted cell arrangements were observed. We studied the early
      cleavage in P. muelleri applying 4D microscopy, fluorescent staining, and
      confocal laser scanning microscopy. To deal with the problem of variation we
      provide statistical evaluations of our data. These show that oblique divisions do
      not represent variational abnormalities. In fact, they reveal that most cells
      divide obliquely from the third cleavage onwards. What is more, in almost all
      cells the axis of the third cleavage is inclined dextrally. The fourth cleavage
      is even stronger sinistrally pronounced. Subsequently, the pattern of alternating
      cleavage orientation is largely restricted to animal and vegetal blastomeres. As
      a result of the obliqueness of divisions, four cells encircle the poles in most
      embryos. Cross furrows are occasionally present. We found no indications for
      radial cleavage in P. muelleri. In contrast, the observed cleavage displays
      several characters consistent with the pattern of spiral cleavage. A close
      relation of phoronid and spiralian cleavage is also suggested by molecular
      phylogenies, allying both groups in the Lophotrochozoa. We suggest our findings
      to represent morphological support for this lophotrochozoan/spiralian affinity of
      Phoronida.

PMID- 23134208
TI  - Quantification of ontogenetic allometry in ammonoids.
AB  - Ammonoids are well-known objects used for studies on ontogeny and phylogeny, but
      a quantification of ontogenetic change has not yet been carried out. Their
      planispirally coiled conchs allow for a study of "longitudinal" ontogenetic data,
      that is data of ontogenetic trajectories that can be obtained from a single
      specimen. Therefore, they provide a good model for ontogenetic studies of
      geometry in other shelled organisms. Using modifications of three cardinal conch
      dimensions, computer simulations can model artificial conchs. The trajectories of
      ontogenetic allometry of these simulations can be analyzed in great detail in a
      theoretical morphospace. A method for the classification of conch ontogeny and
      quantification of the degree of allometry is proposed. Using high-precision cross
      sections, the allometric conch growth of real ammonoids can be documented and
      compared. The members of the Ammonoidea show a wide variety of allometric growth,
      ranging from near isometry to monophasic, biphasic, or polyphasic allometry.
      Selected examples of Palaeozoic and Mesozoic ammonoids are shown with respect to
      their degree of change during ontogeny of the conch.

PMID- 23134209
TI  - Development of the venom ducts in the centipede Scolopendra: an example of
      recapitulation.
AB  - In contrast to previous claims that (a) there is a law of recapitulation and,
      conversely, (b) recapitulation never happens, the evolutionary repatterning of
      development can take many forms, of which recapitulation is one. Here, we add
      another example to the list of case studies of recapitulation. This example
      involves the development of the venom claws (forcipules) in the centipede
      Scolopendra subspinipes mutilans, and in particular the development of the duct
      through which venom flows from the gland that produces it (proximal) to the
      opening called the meatus (distal) through which it is injected into prey. Most
      of the information we present is from early postembryonic stages--these have been
      neglected in previous work on centipede development. We show that the venom ducts
      arise from sutures that are invaginations of the cuticle. In S. s. mutilans, the
      invagination in each forcipule forms into a tubular structure that detaches
      itself from the exoskeleton and moves toward the center of the forcipule. This is
      in contrast to extant Scutigera, and also, probably, Scolopendra's extinct
      Scutigera-like ancestors, where the duct remains attached to the cuticle of
      throughout development. Thus, S. s. mutilans exhibits a recapitulatory
      repatterning of development.

PMID- 23134210
TI  - Evolution of the chelicera: a dachshund domain is retained in the deutocerebral
      appendage of Opiliones (Arthropoda, Chelicerata).
AB  - The proximo-distal axis of the arthropod leg is patterned by mutually
      antagonistic developmental expression domains of the genes extradenticle,
      homothorax, dachshund, and Distal-less. In the deutocerebral appendages (the
      antennae) of insects and crustaceans, the expression domain of dachshund is
      frequently either absent or, if present, is not required to pattern medial
      segments. By contrast, the dachshund domain is entirely absent in the
      deutocerebral appendages of spiders, the chelicerae. It is unknown whether
      absence of dachshund expression in the spider chelicera is associated with the
      two-segmented morphology of this appendage, or whether all chelicerates lack the
      dachshund domain in their chelicerae. We investigated gene expression in the
      harvestman Phalangium opilio, which bears the plesiomorphic three-segmented
      chelicera observed in "primitive" chelicerate orders. Consistent with patterns
      reported in spiders, in the harvestman chelicera homothorax, extradenticle, and
      Distal-less have broadly overlapping developmental domains, in contrast with
      mutually exclusive domains in the legs and pedipalps. However, unlike in spiders,
      the harvestman chelicera bears a distinct expression domain of dachshund in the
      proximal segment, the podomere that is putatively lost in derived arachnids.
      These data suggest that a tripartite proximo-distal domain structure is ancestral
      to all arthropod appendages, including deutocerebral appendages. As a corollary,
      these data also provide an intriguing putative genetic mechanism for the
      diversity of arachnid chelicerae: loss of developmental domains along the proximo
      distal axis.

PMID- 23134211
TI  - Black/African American patients with type 2 diabetes mellitus: study design and
      baseline patient characteristics from a randomized clinical trial of linagliptin.
AB  - OBJECTIVE: In the United States, black/African American individuals are more
      likely than whites to develop type 2 diabetes mellitus (T2DM), and have higher
      rates of complications, but are under-represented in clinical trials. The design
      of a trial comparing the efficacy and safety of the dipeptidyl peptidase-4 (DPP
      4) inhibitor linagliptin 5 mg/day with placebo in this patient group, and the
      characteristics of the patients enrolled are reported. RESEARCH DESIGN AND
      METHODS: This United States, multicenter, 24-week, randomized, double-blind study
      enrolled adults with T2DM who self-reported their race as black or African
      American, were receiving <= 1 oral antidiabetes drug, had a body mass index <= 45
      kg/m(2) and glycosylated hemoglobin (HbA(1c)) of 7.5 - 11% at screening. MAIN
      OUTCOME MEASURES: The primary efficacy endpoint is the change of HbA(1c) from
      baseline to week 24. BASELINE DATA: A total of 226 patients were randomized and
      received >= 1 study drug dose. The mean age was 54 years (standard deviation: 9.9
      years), and 54% were men. The mean HbA(1c) was 8.75% (standard deviation: 1.10%).
      Approximately half the patients (52%) had mild or moderate renal impairment and
      the majority (72%) had hypertension. CONCLUSIONS: To the authors' knowledge, this
      is the first trial of any oral antidiabetes drug specifically conducted in
      black/African American patients.

PMID- 23134212
TI  - The experiences of registered intellectual disability nurses caring for the older
      person with intellectual disability.
AB  - AIM AND OBJECTIVES: To explore the experiences of registered intellectual
      disability nurses caring for the older person with intellectual disability.
      BACKGROUND: Increased longevity for the older person with intellectual disability
      is relatively a new phenomenon with social and medical factors having
      significantly increased the lifespan. The ageing population of people with
      intellectual disability is growing in Ireland, and they are outliving or expected
      to outlive their family carers. DESIGN: A qualitative Heideggerigan
      phenomenological approach allowed the researcher become immersed in the essence
      of meaning and analyse how registered intellectual disability nurses working with
      the older person perceive, experience and express their experience of caring.
      METHODS: After ethical approval was granted, data were collected through semi
      structured interviews from seven participants and were transcribed and analysed
      thematically using Burnard's framework for data analysis. RESULTS: Three key
      themes were identified: 'care delivery', 'inclusiveness' and 'client-focused
      care'. The study highlights the need for effective planning, an integrated
      approach to services and that the registered intellectual disability nurse needs
      to be integrated into the care delivery system within the health service to
      support client and family carers in the home environment. CONCLUSIONS: Overall,
      the study shows the importance of teamwork, proactive planning, inclusion,
      attitudes, individualised care, knowing the person and best practice in providing
      care for older people with intellectual disability. RELEVANCE TO CLINICAL
      PRACTICE: This paper reports on the findings of a study which explored the
      experiences of caring for the older person with intellectual disability.
      Teamwork, proactive planning, client-centred approach and supporting clients
      living at home are important as ageing is inevitable.

PMID- 23134213
TI  - Organic dyes incorporating oligothienylenevinylene for efficient dye-sensitized
      solar cells.
AB  - Two new organic dyes incorporating triphenylamine as a donor and
      oligothienylenevinylene as a bridge have been synthesized. The new dyes cover the
      entire visible region and have a power conversion of up to 6.25%.

PMID- 23134214
TI  - Hepatoprotective effect of DT56a is associated with changes in natural killer T
      cells and regulatory T cells.
AB  - OBJECTIVE: To determine the metabolic and immunological effects of the oral
      administration of DT56a, an enzymatic isolate of soybeans. METHODS: DT56a was
      orally administered to mice in three animal models: leptin deficiency, high-fat
      diet (HFD) supplementation and immune-mediated hepatitis. Liver damage and
      immunological status were assessed. RESULTS: Oral administration of DT56a to
      leptin-deficient (ob/ob) and HFD mice led to a significant reduction in serum
      triglyceride (TG) and total cholesterol (TC) levels. DT56a-treated mice in both
      models exhibited a significant reduction in hepatic levels of TG and marked
      alleviation of glycemic control as indicated by significant decreases in fasting
      blood glucose levels and glucose tolerance tests. The levels of liver enzymes
      were reduced. These metabolic effects were associated with altered distributions
      of regulatory T (Tregs) and natural killer T (NKT) cells. DT56a suppressed the
      immune-mediated liver damage induced by concanavalin A indicated by decreased
      liver enzymes and serum interferon-gamma levels and by improved histology and
      decreased hepatic apoptosis. Oral administration of DT56a also alleviated immune
      mediated hepatitis and affected Tregs and NKT cells. CONCLUSIONS: Oral
      administration of DT56a promotes a hepatoprotective effect associated with an
      alteration in the distribution of Tregs and NKT cells.

PMID- 23134215
TI  - Atypical hemodynamic pattern in fetuses with hypercoiled umbilical cord and
      growth restriction.
AB  - OBJECTIVES: To describe fetal and uterine hemodynamics in intrauterine growth
      restriction (IUGR) fetuses with hypercoiled umbilical cord. METHODS: 102 pregnant
      women with IUGR fetuses were enrolled in the study. In these cases, hemodynamic
      indices and Doppler waveform profiles were evaluated. RESULTS: In seven of the
      enrolled cases of IUGR, we found an anomalous umbilical coiling. They showed
      normal impedance to flow in utero-placental district and abnormal venous
      umbilical cord pulsatility with flow velocity higher than the umbilical artery.
      The ductus venosus showed a reduction of the forward flow and/or a reverse flow
      during atrial contractions. Two of these seven patients had early onset IUGR and
      a particular deteriorating hemodynamic profile with "brain sparing", severe
      reverse flow in the ductus venosus, increased reverse flow in the inferior vena
      cava during atrial contraction and absent flow during the diastole in the
      umbilical arteries. Five patients had late onset of IUGR and three of these did
      not demonstrate these worsening hemodynamic alterations until term. CONCLUSIONS:
      In patients with fetal IUGR and hypercoiling without signs of placental
      insufficiency, we observed an "atypical" feto-maternal hemodynamic pattern. These
      IUGR fetuses with hypercoiling and fetal venous system hemodynamic alteration can
      be at high hypoxic risk.

PMID- 23134216
TI  - Editorial.

PMID- 23134217
TI  - Consumer involvement in topic and outcome selection in the development of
      clinical practice guidelines.
AB  - BACKGROUND: Consumer involvement in guideline development is advocated, but
      minimal participation, such as a nominated consumer representative on a guideline
      working group, can inhibit their decision-making power and contribution. Little
      is known about how to involve consumers more effectively in guideline
      development. OBJECTIVE: To describe a targeted approach for involving consumers
      actively in guideline development, by focusing on topic and outcome selection,
      and to discuss the impact on content and structure of the final guideline.
      DESIGN: Descriptive study. SETTING AND PARTICIPANTS: Patients and carers (n = 24)
      from a tertiary hospital in Sydney attended three structured peer-facilitated
      workshops to complete group-based exercises on topic and outcome selection for
      guidelines for early stage chronic kidney disease. These workshops were run in
      parallel with the guideline-writing group. For each exercise, participants formed
      small groups and facilitated their own discussion, recorded their responses and
      presented them to the wider group. The topics and outcomes identified were fed
      back to the guideline writers. RESULTS: The participants actively engaged in the
      workshop discussions and articulated topics and outcomes they perceived should be
      included in clinical guidelines. Four main changes to guideline-related outputs
      were observed. A new guideline subtopic was introduced, guidelines were consumer
      endorsed, guideline recommendations and suggestions for clinical care were
      augmented with consumer-focused issues, and plain English guidelines were
      developed. CONCLUSIONS: Consumer workshops in parallel and feeding into guideline
      development can be a feasible and effective approach for active consumer
      contribution. This process can inform the development of both consumer-focused
      guidelines for clinicians and specific versions for consumers.

PMID- 23134218
TI  - MicroRNA let-7a inhibits the proliferation and invasion of nonsmall cell lung
      cancer cell line 95D by regulating K-Ras and HMGA2 gene expression.
AB  - MicroRNAs are closely linked to tumor metastasis and let-7a may play a role in
      inhibiting the proliferation, invasion, and metastasis of lung cancer. In vitro,
      we aim to observe the impact of let-7a on the proliferation and invasion of the
      nonsmall cell lung cancer cell line 95D by constructing a lentiviral vector that
      expresses let-7a. Cell proliferation assays and Transwell experiments were used
      to compare the proliferation and invasion of the 95D cell group with let-7a
      overexpressed or inhibited. Real-time polymerase chain reaction and
      immunoblotting analysis were used to compare the expression of K-RAS and HMGA2 at
      mRNA and the protein level in the above groups. The results showed the cells in
      the let-7a overexpressed group were significantly less proliferative and invasive
      than those in the let-7a inhibited group (p < 0.05). K-RAS and HMGA2 mRNA levels
      were significantly higher in the let-7a overexpressed group than those in the let
      7a inhibited group (p < 0.05). However, the protein levels of K-RAS and HMGA2
      were significantly lower in the let-7a overexpressed group than those in the let
      7a inhibited group (p < 0.05). We suppose that let-7a inhibits the proliferation
      and invasion of the cell line 95D by regulating the translation of K-RAS and
      HMGA2 mRNA, not the transcription of the mRNA itself.

PMID- 23134219
TI  - Expression of serum response factor in gastric carcinoma and its molecular
      mechanisms involved in the regulation of the invasion and migration of SGC-7901
      cells.
AB  - Serum response factor (SRF) is a transcription factor of the MADS box family. To
      date, DNA binding sites for SRF [serum response elements (SREs)] have been found
      in the promoters of approximately 50 different genes known to be involved in the
      regulation cell proliferation, differentiation, and apoptosis. Recent studies
      have indicated that SRF plays a role in the development of some tumors, including
      hepatocellular, thyroid, esophageal, and lung carcinomas. However, expression of
      SRF and its roles in gastric carcinoma are unclear. We found SRF to be highly
      expressed in human gastric carcinoma as well as ectopic or reduced expression for
      E-cadherin and beta-catenin. Blockage of SRF expression was found to inhibit
      proliferation, invasion, and migration. We also found that an inhibitor (Y-27632)
      of Rho-associated coiled kinase (ROCK1), a regulator of actin cytoskeleton that
      regulates cell adhesion, migration, and motility, suppressed SRF expression as
      well. These results demonstrate that SRF is involved in the aggressive behavior
      of gastric carcinoma cells. We also found that the inhibition of ROCK1 by Y-27632
      can inhibit the invasion and migration of gastric cells done at least, in part,
      by attenuating SRF expression.

PMID- 23134220
TI  - Usefulness of dual-time point imaging after carbonated water for the
      fluorodeoxyglucose positron emission imaging of peritoneal carcinomatosis in
      colon cancer.
AB  - BACKGROUND: Fluorodeoxygluose (FDG) positron emission/computed tomography
      (PET/CT) is emerging as a useful tool for the diagnosis of peritoneal
      carcinomatosis (PC). In this study, we assessed whether dual-time point imaging
      can improve the accuracy of FDG PET/CT for the diagnosis of PC after colon rectal
      cancer (CRC). METHODS: Thirty-nine patients with past history of CRC were
      evaluated. Whole-Body PET/CT scan was acquired 1 hour after tracer injection. If
      one or more focal areas of increased FDG uptake (standardized uptake value, SUV
      max>2.5) were found in the abdomen, 1 L of carbonated water was orally
      administered to patients and a delayed scan of the abdominal region was acquired
      at 2 hours. The SUV max and the mean Delta (Delta) SUV were calculated. The
      scintigraphic results were compared with the results of colonoscopy and histology
      and with the clinical follow-up. RESULTS: Thirteen out of the 39 patients did not
      show any significant area of FDG uptake at the whole-body scan. The remaining 26
      patients showed an overall number of 27 sites of focal increased uptake, showing
      a mean SUV max of 6.5+3.3. Late scan of the abdomen showed vanishing spots in 11
      cases. Focal and increasing FDG uptake was found in 15 subjects (for an overall
      number of 16 sites) with SUV max of 15.6+4 and mean Delta SUV of +26.3%+/-7.5%.
      In these cases, final diagnosis was PC in 10 patients (according to cytology or
      histology) and dysplastic polyp in 5 cases. No significant difference in Delta
      SUV was found between patients with PC and those with polypoid formations.
      CONCLUSIONS: According to our results, dual-time point imaging after carbonated
      water may increase the accuracy of FDG PET/CT for the imaging of PC in patients
      affected by CRC.

PMID- 23134221
TI  - Inhibition of lung adenocarcinoma transfected with interleukin 28A recombinant
      adenovirus (Ad-mIFN-lambda2) in vivo.
AB  - Abstract Type III interferon (IFN-lambda) is a novel member of the interferon
      family, which preferentially promotes antiviral responses from epithelial cells
      and cooperates with type I IFNs in the clearance of viral infections. However,
      the effect of mIFN-lambda2 to the LA795 lung adenocarcinoma cell is largely
      unknown. In this study, we transfected Ad-mIFN-lambda2 vector into LA795 tumor
      bearing mice to explore the effect of mIFN-lambda2 on the proliferation of LA795
      lung adenocarcinoma cell and on the immune response of the mice. Transfected by
      Ad-mIFN-lambda2 vector, a significant decrease in the tumor growth, the
      subcutaneous tumor necrosis, cystic degeneration, and tumor apoptosis were more
      evident; at the same time, mIFN-lambda2 protein and gene were significantly more
      expressed. And, flow cytometry analysis suggested that CD3(+)CD4(+),
      CD3(+)CD8(+), and NK (CD3(-)CD49(+)) cells were all significantly increased after
      transfected by Ad-mIFN-lambda2. The study demonstrated that recombinant Ad-mIFN
      lambda2 transfection effectively inhibited the growth of LA795 lung
      adenocarcinoma cell, which may work through inducing apoptosis of tumor cell and
      regulating cell immune response.

PMID- 23134222
TI  - Impact of thiamine deficiency on T-cell dependent and T-cell independent antibody
      production in lake trout.
AB  - Lake trout Salvelinus namaycush on thiamine-replete and thiamine-depleted diets
      were evaluated for the effects of thiamine status on in vivo responses to the T
      dependent antigen trinitophenol (TNP)-keyhole limpet hemocyanin (TNP-KLH), the T
      independent antigen trinitrophenol-lipolysaccaharide (TNP-LPS), or Dulbecco's
      phosphate-buffered saline (DPBS; negative control fish). Plasma antibody
      concentrations were evaluated for possible differences in total anti-TNP activity
      as well as differences in response kinetics. Associations between anti-TNP
      activity and muscle and liver thiamine concentrations as well as ratios of muscle
      to-liver thiamine to anti-TNP activity were also examined. Thiamine-depleted lake
      trout that were injected with TNP-LPS exhibited significantly more anti-TNP
      activity than thiamine-replete fish. The depleted fish injected with TNP-LPS also
      exhibited significantly different response kinetics relative to thiamine-replete
      lake trout. No differences in activity or kinetics were observed between the
      thiamine-replete and -depleted fish injected with TNP-KLH or in the DPBS negative
      controls. Anti-TNP activity in thiamine-depleted lake trout injected with TNP-KLH
      was positively associated with muscle thiamine pyrophosphate (thiamine
      diphosphate; TPP) concentration. A negative association was observed between the
      ratio of muscle-to-liver TPP and T-independent responses. No significant
      associations between anti-TNP activity and tissue thiamine concentration were
      observed in the thiamine-replete fish. We demonstrated that thiamine deficiency
      leads to alterations in both T-dependent and T-independent immune responses in
      lake trout.

PMID- 23134225
TI  - Editorial comment from Dr Herrel and Dr Canter to association of renal
      nephrometry score with outcomes of minimally invasive partial nephrectomy.

PMID- 23134226
TI  - Relationship between fertilization rate and early apoptosis in sperm population
      of infertile individuals.
AB  - Integrity of the sperm membrane, of which phosphatidyl serine (PS) plays a
      central role, is essential for fertilization. The externalisation of PS (EPS)
      occurs during capacitation and the acrosome reaction. EPS, from the inner to the
      outer membrane, is considered as a sign of early apoptosis. Therefore, EPS may
      have a dual function in sperm. This study has evaluated the relationship between
      EPS and fertilization, embryo quality and pregnancy outcomes in couples who were
      candidates for ICSI. Semen samples were collected from 43 ICSI candidates and
      assessed according to World Health Organization guidelines for semen parameters.
      EPS was assessed by Annexin V and propidium iodide (PI) staining. Protamine
      deficiency was assessed by chromomycin A3 (CMA3) staining. A significant positive
      correlation was observed between the percentages of fertilization and annexin
      positive PI-negative (An(+)PI(-)) sperm. There was a significant negative
      correlation between the percentages of protamine-deficient sperm with the
      percentage of fertilization. In addition, the percentage of An(+)PI(-) sperm in
      individuals with fertilization rates higher and lower than 50% significantly
      differed. The percentage of annexin-positive PI-positive (An(+)PI(+)) sperm in
      semen of the partners of pregnant women significantly differed from the partners
      of nonpregnant women. In conclusion, if An(+)PI(-) is a sign of capacitation and
      An(+)PI(+) is a sign of apoptosis, the results suggest that semen samples with a
      higher ability to undergo capacitation have a higher chance to result in
      successful fertilization post-ICSI. The presence of a high percentage of
      apoptotic sperm in the insemination sample before capacitation may reduce the
      chances of pregnancy. 

PMID- 23134227
TI  - Benzofuroxane derivatives as multi-effective agents for the treatment of
      cardiovascular diabetic complications. Synthesis, functional evaluation, and
      molecular modeling studies.
AB  - Diabetes mellitus is the major risk factor for cardiovascular disorders. Aldose
      reductase, the rate-limiting enzyme of the polyol pathway, plays a key role in
      the pathogenesis of diabetic complications. Accordingly, inhibition of this
      enzyme is emerging as a major therapeutic strategy for the treatment of
      hyperglycemia-induced cardiovascular pathologies. In this study, we describe a
      series of 5(6)-substituted benzofuroxane derivatives, 5a-k,m, synthesized as
      aldose reductase inhibitors. Besides inhibiting efficiently the target enzyme, 5a
      k,m showed additional NO donor and antioxidant properties, thus emerging as novel
      multi-effective compounds. The benzyloxy derivative 5a, the most promising of the
      whole series, showed a well-balanced, multifunctional profile consisting of
      submicromolar ALR2 inhibitory efficacy (IC50=0.99+/-0.02 MUM), significant and
      spontaneous NO generation properties, and excellent hydroxyl radical scavenging
      activity. Computational studies of the novel compounds clarified the aldose
      reductase inhibitory profile observed, thus rationalizing structure-activity
      relationships of the whole series.

PMID- 23134228
TI  - The additive diagnostic role of coronary flow reserve in noninvasive evaluation
      of coronary stenosis on left descending artery previously detected by multislice
      computed tomography.
AB  - PURPOSE: Multislice computed coronary angiography (MSCT) provides valuable
      morphological information about coronary artery disease, but precise
      quantification of coronary stenosis remains difficult. Transthoracic color
      Doppler echocardiography (TDE) gives a new insight into the functional
      significance of coronary luminal narrowing. We have tried to assess the additive
      value of coronary flow reserve (CFR) determined by TDE over MSCT in prediction of
      a significant stenosis on the left anterior descending artery (LAD) using the
      invasive coronary angiography (ICA) as a reference method. METHODS: This
      prospective study included 63 patients in stable cardiac status with previously
      detected atherosclerotic lesions on LAD by MSCT. CFR assessment by TDE with
      adenosine infusion was obtained to all patients (feasibility was 96.92%). CFR was
      determined as ratio between the peak diastolic flow velocity during adenosine
      infusion and at basal condition, a cutoff value indicating significant stenosis
      was <2. ICA was preformed to all patients 24-48 hours after CFR. RESULTS: MSCT
      had sensitivity of 86.36%, specificity 53.66%, positive predictive value 50.00%,
      negative predictive value 88.00%, and diagnostic accuracy of 65.07% in detection
      of significant LAD stenosis. CFR had sensitivity 81.81%, specificity 97.06%,
      positive predictive value 94.74%, negative predictive value 89.19%, and
      diagnostic accuracy of 91.07%. When the results of both methods were agreed
      diagnostic accuracy was improved to 92.72%. CONCLUSION: Additional assessment of
      CFR by TDE increase diagnostic accuracy of MSCT angiography in detection of
      significant coronary artery lesions.

PMID- 23134229
TI  - Metabolic and biochemical effects of low-to-moderate alcohol consumption.
AB  - BACKGROUND: Alcohol consumption has multiple biochemical consequences. Only a few
      of these are useful as diagnostic markers, but many reflect potentially harmful
      or beneficial effects of alcohol. Average consumption of 2 to 4 drinks per day is
      associated with lower overall or cardiovascular mortality risk than either lower
      or higher intake. We have analyzed the dose-response relationships between
      reported alcohol consumption and 17 biomarkers, with emphasis on intake of up to
      3 drinks per day. METHODS: Biochemical tests were performed on serum from 8,396
      study participants (3,750 men and 4,646 women, aged 51 +/- 13 years, range 18 to
      93) who had provided information on alcohol consumption in the week preceding
      blood collection. RESULTS: Gamma glutamyl transferase, alanine aminotransferase,
      aspartate aminotransferase, carbohydrate-deficient transferrin, urate, ferritin,
      and bilirubin showed little or no change with alcohol consumption below 2 to 3
      drinks per day, but increased with higher intake. High-density lipoprotein
      cholesterol and albumin showed increasing results, and insulin showed decreasing
      results, across the entire range of alcohol use. Biphasic responses, where
      subjects reporting 1 to 2 drinks per day had lower results than those reporting
      either more or less alcohol use, occurred for triglycerides, glucose, C-reactive
      protein, alkaline phosphatase, and butyrylcholinesterase. Increasing alcohol use
      was associated with decreasing low-density lipoprotein cholesterol (LDL-C) in
      younger women, but higher LDL-C in older men. CONCLUSIONS: Some markers show
      threshold relationships with alcohol, others show continuous ones, and a third
      group show biphasic or U-shaped relationships. Overall, the biochemical sequelae
      of low-to-moderate alcohol use are consistent with the epidemiological evidence
      on morbidity and mortality.

PMID- 23134230
TI  - Serum immunoglobulin A/C3 ratio predicts progression of immunoglobulin A
      nephropathy.
AB  - AIM: The serum immunoglobulin A (IgA)/C3 ratio has been shown to be a good
      predictor of histological lesions and prognosis for patients with IgA nephropathy
      (IgAN) in Japanese. But its validity in the Chinese population is unclear. We
      sought to explore the long-term outcomes of IgAN, its clinical and
      histopathological predictors in Chinese patients. In particular, the role of
      serum IgA/C3 ratio in the course of IgAN was addressed. METHODS: A total of 217
      biopsy-diagnosed IgAN patients were recruited into this prospective cohort with a
      mean follow-up of 36 months (25-75th percentile, 27-48). Sociodemographics, serum
      IgA/C3 level, other clinical examinations and Lee's histological grade were
      measured. The patients with a decline of estimated glomerular filtration rate
      (eGFR) > 50% or developing end-stage renal disease (ESRD) were defined as
      progression. RESULTS: A total of 21 patients was found to progress (9.7%). In
      multivariate analysis, renal end point of IgAN was significantly predicted by
      proteinuria >=1 g/day (relative risk (RR) = 2.65, 95% confidence interval (CI)
      1.01-7.68), hypertension (RR = 3.15, 95% CI 1.07-9.29), higher Lee's histological
      grade (RR = 4.67, 95% CI 1.43-15.25) and serum IgA/C3 ratio >= 3.32 (RR = 4.31,
      95% CI 1.33-13.96). CONCLUSION: A proportion of patients with IgAN developed end
      stage renal disease in a Chinese group. In addition to some traditional risk
      factors, we also confirmed that IgA/C3 ratio is a useful predictor of poor
      outcomes of IgAN in Chinese patients.

PMID- 23134231
TI  - Collagenous colitis with mucosal tears in two proton pump inhibitors and non
      steroidal naive patients who developed metachronous cancer.

PMID- 23134232
TI  - Raman spectroscopic characterization of structural changes in heated whey protein
      isolate upon soluble complex formation with pectin at near neutral pH.
AB  - The mechanism leading to an alteration of heat aggregation of whey protein
      isolate (WPI) in the presence of pectin was investigated by assessing structural
      changes of proteins using Raman spectroscopy. WPI solutions were heated without
      or with pectin at 0.015-0.2 pectin to WPI weight ratios and pH 6.0-6.4. In the
      absence of pectin, thermal denaturation resulted in a loss of alpha-helical
      structure and an increase in beta-structure and random coils of protein. At pH
      6.0 and 6.2, heat aggregation of WPI was suppressed when pectin (0.05-0.15 pectin
      to WPI ratios) was present as shown by a decrease in turbidity and particle size.
      Concomitantly, changes in the secondary structures were reduced, indicating the
      enhanced stability of protein structure by pectin. Raman results also revealed
      that alpha-helix and beta-sheet are dominant structures in heated WPI--pectin
      soluble complexes, and hydrogen bonding between biopolymers increased. The effect
      of pectin was pH dependent, indicating the involvement of electrostatic
      interaction.

PMID- 23134233
TI  - Assessment of degradation byproducts and NDMA formation potential during UV and
      UV/H2O2 treatment of doxylamine in the presence of monochloramine.
AB  - UV-C radiation is the U.S. EPA recommended technology to remove N
      nitrosodimethylamine (NDMA) during drinking and recycled water production.
      Frequently, H(2)O(2) is added to the treatment to remove other recalcitrant
      compounds and to prevent NDMA reformation. However, the transformation of NDMA
      precursors during the UV and UV/H(2)O(2) process and the consequences for NDMA
      formation potential are currently not well understood, in particular in the
      presence of monochloramine. In this study, doxylamine has been chosen as a model
      compound to elucidate its degradation byproducts in the UV and UV/H(2)O(2)
      process and correlate those with changes to the NDMA formation potential. This
      study shows that during UV treatment in the presence and absence of
      monochloramine, NDMA formation potential can be halved. However, an increase of
      more than 30% was observed when hydrogen peroxide was added. Ultrafast liquid
      chromatography coupled to quadrupole-linear ion trap mass spectrometer was used
      for screening and structural elucidation of degradation byproducts identifying 21
      chemical structures from the original parent compound. This work shows that
      further oxidation of NDMA precursors does not necessarily lead to a decrease in
      NDMA formation potential. Degradation byproducts with increased electron density
      in the vicinity of the dimethylamino moiety, for example induced by
      hydroxylation, may have a higher yield of nucleophilic substitution and
      subsequent NDMA formation compared to the parent compound during chloramination.
      This work demonstrates the need to consider the formation of oxidation byproducts
      and associated implications for the control and management of NDMA formation in
      downstream processes and distribution when integrating oxidative treatments into
      a treatment train generating either drinking water or recycled water for potable
      reuse.

PMID- 23134234
TI  - Carbohydrate-protein coingestion improves multiple-sprint running performance.
AB  - Acute carbohydrate-protein ingestion has been shown to improve steady-state
      endurance performance. This study compared the effects of carbohydrate and
      carbohydrate-protein ingestion on self-regulated simulated multiple-sprint sport
      performance. Nine participants completed two trials of a modified Loughborough
      Intermittent Shuttle Test involving 4 x 15 min blocks of regulated exercise
      followed by 2 x 15 min blocks of self-regulated exercise. Participants consumed
      2.5 ml . kg(-1) of an 8% carbohydrate (CHO trial) or 6% carbohydrate plus 2% whey
      protein beverage (CHO-P trial) every 15 minutes. Distance covered (4.2%) and
      maximal speed (6.1%) decreased (P < 0.05) in the final 15 min of exercise, and
      whilst not significant, carbohydrate-protein elicited a very likely moderate
      (2.5: 90% confidence limits; +/-1.4%) and possibly small (1.9: +/-3.3%)
      improvement in each variable, respectively. Average running speed declined in the
      final 15 min of the CHO trial only (P = 0.002), with protein providing a likely
      small improvement (2.7%: +/-2.5%). No differences (P > 0.05) between beverages
      were observed in body mass or plasma volume change, urine volume, heart rate, gut
      fullness, rating of perceived exertion (RPE), blood glucose or serum insulin.
      Blood urea concentration increased in the CHO-P trial only (mean +/- SD: 45.4 +/-
      9.9 c.f. 39.2 +/- 11.4 g . dL(-1), P = 0.003). These findings show carbohydrate
      protein ingestion is likely to enhance multiple-sprint sport exercise performance
      above carbohydrate, potentially through altered central fatigue or increased
      protein oxidation.

PMID- 23134235
TI  - Cardioprotective effect of grape-seed proanthocyanidins on doxorubicin-induced
      cardiac toxicity in rats.
AB  - CONTEXT: Doxorubicin (Dox) is an anthracycline antibiotic used as anticancer
      agent. However, its use is limited due to its cardiotoxicity which is mainly
      attributed to accumulation of reactive oxygen species. OBJECTIVE: This study was
      conducted to assess whether the antioxidant, proanthocyanidins (Pro) can
      ameliorate Dox-induced cardiotoxicity in rats. MATERIALS AND METHODS: Male
      Sprague-Dawely rats were divided into four groups. Group I was control. Group II
      received Pro (70 mg/kg, orally) once daily for 10 days. Group III received
      doxorubicin 15 mg/kg i.p. as a single dose on the 7th day and Group IV animals
      were treated with Pro once daily for 10 days and Dox on the 7th day. The
      parameters of study were serum biomarkers, cardiac tissue antioxidant status,
      ECG, and effect on aconitine-induced cardiotoxicity. RESULTS: Cardiac toxicity of
      doxorubicin was manifested as a significant increase in heart rate, elevation of
      the ST segment, prolongation of the QT interval and an increase in T wave
      amplitude. In addition, Dox enhanced aconitine-induced cardiotoxicity by a
      significant decrease in the aconitine dose producing ventricular tachycardia
      (VT). Administration of Pro significantly suppressed Dox-induced ECG changes and
      normalized the aconitine dose producing VT. The toxicity of Dox was also
      confirmed biochemically by significant elevation of serum CK-MB and LDH
      activities as well as myocardial MDA and GSH contents and decrease in serum
      catalase and myocardial SOD activities. Administration of Pro significantly
      suppressed these biochemical changes. DISCUSSION AND CONCLUSION: These results
      suggest that proanthocyanidins might be a potential cardioprotective agent
      against Dox-induced cardiotoxicity due to its antioxidant properties.

PMID- 23134236
TI  - Dendritic brushes under good solvent conditions: a simulation study.
AB  - The structural properties of polymer brushes, formed by dendron polymers up to
      the third generation, were studied by means of Brownian dynamics simulations for
      the macroscopic state of good solvent. The distributions of polymer units, of the
      free ends, of the dendrons centers of mass, and of the units of every dendritic
      generation and the radii of gyration necessary for the understanding of the
      internal stratification of brushes were calculated. Previous self-consistent
      field theory numerical simulations of first-generation dendritic brushes
      suggested that at high grafting densities two kinds of populations are evident,
      one of short dendrons having weakly extended spacers and another with tall
      dendrons having strongly stretched spacers. These Brownian dynamics calculations
      provided a more complicated picture of dendritic brushes, revealing different
      populations of short, tall, and in some cases intermediate height dendrons,
      depending on the dendron generation and spacer length. The scaling dependence of
      the height and the span of the dendritic brush on the grafting density and other
      parameters were found to be in good agreement with existing theoretical results
      for good solvents.

PMID- 23134237
TI  - How do relatives of persons with dementia experience their role in the patient
      participation process in special care units?
AB  - AIMS AND OBJECTIVE: To explore the role of relatives in the patient participation
      process for persons with dementia living in special care units in Norwegian
      nursing homes, with focus on everyday life. BACKGROUND: Studies exploring the
      experience of relatives of persons with dementia as to their role in the patient
      participation process are limited. DESIGN: The study had an explorative grounded
      theory design. METHOD: Data collection was carried out by interviews with twelve
      close relatives. Simultaneously, data analysis was performed with open, axial and
      selective coding. RESULTS: The relatives' role in the patient participation
      process was experienced as transitions between different roles to secure the
      resident's well-being, which was understood as the resident's comfort and
      dignity. This was the ultimate goal for their participation. The categories
      'being a visitor', 'being a spokesperson', 'being a guardian' and 'being a link
      to the outside world' described the different roles. Different situations and
      conditions triggered different roles, and the relatives' trust in the personnel
      was a crucial factor. CONCLUSIONS: The study has highlighted the great importance
      of relatives' role in the patient participation process, to secure the well-being
      of residents living in special care units. Our findings stress the uttermost need
      for a high degree of competence, interest and commitment among the personnel
      together with a well functioning, collaborative and cooperative relationship
      between the personnel and the relatives of persons with dementia. The study
      raises several important questions that emphasise that more research is needed.
      RELEVANCE TO CLINICAL PRACTICE: Relatives need to be seen and treated as a
      resource in the patient participation process in dementia care. More attention
      should be paid to initiating better cooperation between the personnel and the
      relatives, as this may have a positive impact both on the residents' and the
      relatives' well-being.

PMID- 23134238
TI  - Is there a potential link between indoor chlorinated pool environment and airway
      remodeling/inflammation in swimmers?

PMID- 23134239
TI  - Elite athletes with asthma: is the management goal total control?

PMID- 23134241
TI  - The PROPELTM steroid-releasing bioabsorbable implant to improve outcomes of sinus
      surgery.
AB  - Chronic rhinosinusitis is widely recognized as one of the most common chronic
      disease entities. Since its introduction in the USA in 1985, the role of
      functional endoscopic sinus surgery as an adjunct to medical therapy in the
      treatment of chronic sinus disease has expanded significantly. Corticosteroids
      are an integral part of the management of the mucosal inflammation in chronic
      rhinosinusitis, and it is generally accepted that existing routes of delivery to
      the sinus mucosa are suboptimal. The PROPELTM steroid-releasing implant
      (Intersect ENT) initiates a new era in topical therapy providing controlled drug
      delivery directly to the sinus tissue. The mometasone furoate-releasing implant
      has been clinically proven to prevent obstruction of the ethmoid sinus following
      surgery and recently received US FDA approval. Initial studies demonstrate
      improved postoperative healing with the device, thus reducing the need for
      additional surgical procedures such as adhesion lysis and systemic steroids.

PMID- 23134242
TI  - New insights into gene-specific management in cystic fibrosis from the 2012
      European Cystic Fibrosis Conference.
AB  - 35th European Cystic Fibrosis Conference   The Convention Centre, Dublin,
      Ireland, 6-9 June 2012   More than 2400 delegates attended the 35th European
      Cystic Fibrosis Conference held in Dublin between 6 and 9 June 2012. More than
      525 abstracts were presented at the conference. There were 30 symposia with four
      speakers at each, in addition to numerous workshops where researchers had the
      opportunity to present their work into scientific, clinical and psychological
      aspects of cystic fibrosis care. Keynote speakers provided state of the art
      lectures in two plenary sessions. This report highlights two important areas in
      the field of molecular genetics and the need for new and validated clinical trial
      end points.

PMID- 23134243
TI  - Pulmonary hypertension topics.
AB  - The International Society for Heart and Lung Transplantation, 32nd Annual Meeting
      and Scientific Sessions   Prague, Czech Republic, 18-21 April 2012   Interest in
      pulmonary hypertension (PH) continues to grow within the International Society
      for Heart and Lung Transplantation (ISHLT). The PH program at the 32nd annual
      meeting held on 18-21 April 2012 in Prague, Czech Republic, was particularly
      strong, with 56 accepted abstracts and five symposia dealing with PH and right
      ventricular function. In this report, we will summarize selected oral abstract
      presentations dealing with a broad array of topics on PH and right ventricular
      function. These include original research on registries, prognosis, disease
      management, clinical trials, novel therapies, echocardiographic assessments and
      exercise hemodynamics.

PMID- 23134244
TI  - New ideas in lung regeneration: a personal view from Estoril.
AB  - 10th ERS Lung Science Conference--rebuilding a diseased lung: repair and
      regeneration Estoril, Portugal, 30 March-1 April 2012 The 10th ERS Lung Science
      Conference, held in Estoril, Portugal, focused on rebuilding a diseased lung:
      repair and regeneration, seeking to understand, with some amount of precision,
      how the processes by which the vastly complex self-assembling, self-repairing
      machine that is a human lung actually develops from a few cells in the embryo,
      repairs itself or fails to and succumbs to disease. Thus, the major research
      themes focused on lung development, lung stem and progenitor cell populations,
      regenerative signaling mechanisms and tissue engineering and transplantation.

PMID- 23134245
TI  - Considerations and challenges for eliminating asthma disparities in children.
AB  - Evaluation of: Woods ER, Bhaumik U, Sommer SJ et al. Community asthma initiative:
      evaluation of a quality improvement program for comprehensive asthma care.
      Pediatrics 129(3), 465-472 (2012).   The Community Asthma Initiative is an
      evidence-based asthma intervention that is effective in improving quality of life
      for inner-city African-American and Latino children, while showing a return on
      investment of US$1.46, due to lower asthma-related hospital costs. The program
      provides an example of a comprehensive asthma management model that could be
      disseminated nationally with the goal of reducing asthma disparities. The health
      of children disproportionately affected by asthma could also be improved by
      integrating a broad range of housing policies into evidence-based asthma
      interventions in communities with high-pediatric asthma morbidity. Such
      interventions will be costly, but are likely to achieve long-term sustainable
      health benefits for children with asthma.

PMID- 23134246
TI  - State of the art: strategies for extracorporeal membrane oxygenation in
      respiratory failure.
AB  - Extracorporeal membrane oxygenation (ECMO) is an important rescue therapy for
      patients with cardiac and/or respiratory failure, with a growing body of
      literature supporting its use. Despite widespread use of ECMO, there remains a
      paucity of data on optimal management strategies for ECMO patients. Management of
      ECMO patients involves an understanding of the complex interaction between this
      technology and the critically ill patients being supported. ECMO providers
      typically rely on a combination of consensus guidelines and institutional
      experience to make management decisions. Substantial controversy continues to
      exist regarding many elements of ECMO management, including seemingly
      straightforward decisions such as the initial implementation of this technology.
      In addition, there are multiple providers involved in the management of ECMO
      patients who must be co-ordinated for this supportive therapy to be most
      effective. This manuscript provides an overview of current techniques for
      treating respiratory ECMO patients.

PMID- 23134247
TI  - Pulmonary rehabilitation and acute exacerbations of COPD.
AB  - Acute exacerbations are major events in the natural history of chronic
      obstructive pulmonary disease (COPD) and are associated with increased morbidity
      and mortality. Although pulmonary rehabilitation increases exercise capacity,
      reduces dyspnea and improves health-related quality of life, the effects on risk
      of future exacerbations (and by extension, healthcare utilization) are less well
      documented. Furthermore, there has been a growing evidence base to support
      provision of pulmonary rehabilitation in the acute phase of COPD, for example,
      shortly after hospitalization for an acute exacerbation. This article reviews the
      role of pulmonary rehabilitation in the prevention and treatment of acute
      exacerbations of COPD.

PMID- 23134248
TI  - Management and prevention of ventilator-associated pneumonia caused by multidrug
      resistant pathogens.
AB  - Ventilator-associated pneumonia (VAP) due to multidrug-resistant (MDR) pathogens
      is a leading healthcare-associated infection in mechanically ventilated patients.
      The incidence of VAP due to MDR pathogens has increased significantly in the last
      decade. Risk factors for VAP due to MDR organisms include advanced age,
      immunosuppression, broad-spectrum antibiotic exposure, increased severity of
      illness, previous hospitalization or residence in a chronic care facility and
      prolonged duration of invasive mechanical ventilation. Methicillin-resistant
      Staphylococcus aureus and several different species of Gram-negative bacteria can
      cause MDR VAP. Especially difficult Gram-negative bacteria include Pseudomonas
      aeruginosa, Acinetobacter baumannii, carbapenemase-producing Enterobacteraciae
      and extended-spectrum beta-lactamase producing bacteria. Proper management
      includes selecting appropriate antibiotics, optimizing dosing and using timely de
      escalation based on antiimicrobial sensitivity data. Evidence-based strategies to
      prevent VAP that incorporate multidisciplinary staff education and collaboration
      are essential to reduce the burden of this disease and associated healthcare
      costs.

PMID- 23134249
TI  - Morbidities associated with obstructive sleep apnea.
AB  - Obstructive sleep apnea (OSA)-induced biological changes include intermittent
      hypoxia, intermittent hypercapnia, intrathoracic pressure changes, sympathetic
      activation and sleep fragmentation. OSA can cause metabolic dysregulation,
      endothelial dysfunction, systemic inflammation, oxidative stress and
      hypercoagulation, and neurohumoral changes. There is evidence suggesting that OSA
      is independently associated with metabolic syndrome. OSA has been shown to
      increase the risk for systemic hypertension, pulmonary vascular disease, ischemic
      heart disease, cerebral vascular disease, congestive heart failure and
      arrhythmias. Although there are evidences accumulating that there may be a causal
      relationship between OSA and cardiovascular disorders, there is a need for more
      data from randomized controlled intervention trials to confirm this relationship.
      Many risk factors of OSA (age, male gender and obesity) are also known risk
      factors for cardiovascular disease. Severe OSA-hypopnea significantly increases
      the risk of fatal and nonfatal cardiovascular events in both men and women, and
      continuous positive airway pressure treatment reduces this risk in both.
      Neurocognitive consequences of OSA include daytime sleepiness, loss of alertness,
      memory deficit, reduced vigilance, impaired executive function, increased risk
      for automobile and occupational accidents, and decreased quality of life.

PMID- 23134251
TI  - Inhibiting the protein ubiquitination cascade by ubiquitin-mimicking short
      peptides.
AB  - Short heptapeptides were identified to function as ubiquitin (UB) mimics that are
      activated by E1 and form thioester conjugates with E1, E2, and HECT type E3
      enzymes. The activities (k(cat)/K(1/2)) of E1 with the UB-mimicking peptides are
      130-1,400-fold higher than the equally long peptide with the native C-terminal
      sequence of UB. By forming covalent conjugates with E1, E2, and E3 enzymes, the
      UB-mimicking peptides can block the transfer of native UB through the cascade.

PMID- 23134252
TI  - Diagnosis and therapy of pancreas divisum by ERCP: a single center experience.
AB  - OBJECTIVE: The aim of this study was to determine the diagnosis and endoscopic
      management of pancreas divisum with results from long-term experience at our
      institution. METHODS: A prospectively collected database of all patients who
      underwent endoscopic retrograde cholangiopancreatography (ERCP) with the
      diagnosis of pancreas divisum at our institution from January 2001 to April 2010
      was retrospectively analyzed. RESULTS: A total of 45 patients were identified
      with pancreas divisum with 62 ERCP procedures. The major indication for ERCP
      included pancreatitis in 33 patients (73.3%), of whom 18 had idiopathic recurrent
      acute pancreatitis, 8 had recurrent pancreatic-type pain and 7 had chronic
      pancreatitis. The median size of the incision of sphincterotomy was 5 mm (range 3
      8 mm). In all 37 patients (82.2%) underwent placement of stent into the dorsal
      pancreatic duct, with a median stent size of 5 Fr by 7 cm (range 3-10 Fr by 3-12
      cm). The overall response rate was 75.8%. CONCLUSIONS: The frequency of finding
      pancreas divisum during ERCP varies among institutions and is low compared with
      the autopsy series, given that many patients may remain asymptomatic or might not
      undergo ERCP even if the symptoms develop. Our study is the first to describe
      specific procedure-related details during therapeutic endoscopy for pancreas
      divisum.

PMID- 23134254
TI  - Alterations in early filling dynamics predict the progression of compensated
      pressure overload hypertrophy to heart failure better than abnormalities in
      midwall systolic shortening.
AB  - To evaluate whether the evolution of compensated pressure overload hypertrophy
      (POH) to overt heart failure (HF) is better predicted by systolic versus
      diastolic dysfunction, serial echocardiography was performed 1, 2, 4, 8, and 10
      weeks after suprarenal aortic banding in 52 rats. One week after banding, at
      comparable extent of left ventricular hypertrophy and geometry, myocardial and
      chamber systolic performance, a restrictive filling pattern was well evident only
      in rats which eventually developed overt HF, according to postmortem lung weight.
      In experimental POH, early assessment of transmitral flow velocity allows to
      predict a faster progression toward HF. 

PMID- 23134255
TI  - The importance of screening and treating depression in all women.

PMID- 23134256
TI  - 'You just change the channel if you don't like what you're going to hear':
      gamblers' attitudes towards, and interactions with, social marketing campaigns.
AB  - OBJECTIVES: To investigate how gamblers interact with, and respond to, downstream
      social marketing campaigns that focus on the risks and harms of problem gambling
      and/or encourage help seeking. METHODS: Qualitative study of 100 gamblers with a
      range of gambling behaviours (from non-problem to problem gambling). We used a
      Social Constructivist approach. Our constant comparative method of data
      interpretation focused on how participants' experiences and interactions with
      gambling influenced their opinions towards, and interactions with social
      marketing campaigns. RESULTS: Three key themes emerged from the narratives. (i)
      Participants felt that campaigns were heavily skewed towards encouraging
      individuals to take personal responsibility for their gambling behaviours or were
      targeted towards those with severe gambling problems. (ii) Participants described
      the difficulty for campaigns to achieve 'cut through' because of the overwhelming
      volume of positive messages about the benefits of gambling that were given by the
      gambling industry. (iii) Some participants described that dominant discourses
      about personal responsibility prevented them from seeking help and reinforced
      perceptions of stigma. CONCLUSIONS AND IMPLICATIONS: Social marketing campaigns
      have an important role to play in the prevention of gambling risk behaviours and
      the promotion of help seeking. Social marketers should explore how to more
      effectively target campaigns to different audience segments, understand the role
      of environmental factors in undermining the uptake of social marketing strategies
      and anticipate the potential unforeseen consequences of social marketing
      strategies.

PMID- 23134263
TI  - Investigating the effects of a hydrolytically stable hapten and a Th1 adjuvant on
      heroin vaccine performance.
AB  - We challenged the performance of our previous heroin vaccine with a similar
      vaccine containing a more hydrolytically stable hapten analogue and a Th1
      adjuvant (CpG ODN). Our results indicate that the elements of our previous
      vaccine are essential for its anti-heroin potency, i.e., a chemically labile
      hapten and an exclusively Th2 humoral response elicited by alum. Such design
      elements are critical for producing next-generation heroin vaccines.

PMID- 23134264
TI  - Can the incidence of gastric cancer be reduced in the new century?
AB  - Gastric cancer (GC) is one of the most common cancers in the world. The incidence
      and mortality rate of GC vary among different countries. It is suggested that GC
      is the result of the interaction between Helicobacter pylori (H. pylori)
      infection and the genetic and environmental factors in the host. H. pylori
      infection is the trigger of intestinal gastric adenocarcinoma. The incidence of
      GC is highest in East Asia and East Europe, but much lower in Africa; however, H.
      pylori infection is commonly seen in Africa, which is known as the African
      enigma. The 5-year survival of early GC is far better than that of advanced GC. A
      high detection rate of early GC could help us to conquer GC. A decreasing trend
      of GC incidence has been witnessed worldwide. With the improvement of living
      conditions and the achievements of scientific research, it seems possible that
      there will be a further reduction in the incidence of GC in the new century.

PMID- 23134265
TI  - Guided gingival fibroblast attachment to titanium surfaces: an in vitro study.
AB  - AIM: To assess the potential of gingival fibroblasts to attach in a predetermined
      linear orientation to a nano-topography of aligned fibres on titanium surfaces
      and determine the ability of such cells to deposit aligned collagen fibre matrix.
      MATERIALS AND METHODS: smooth glass and rough titanium substrates were coated
      with polytetrafluoroethylene (PTFE) nano-fibres. Ammonia plasma treatment was
      used to modify the surface chemistry. Human gingival fibroblasts were cultured on
      substrates and orientation and collagen deposition was assessed. RESULTS:
      Straight, unidirectional, parallel PTFE nano-fibres were deposited over the
      titanium features. By 7 days, the majority of cells were observed to orient to
      untreated fibres despite the presence of competing titanium surface features. On
      plasma-treated fibre-coated titanium substrates, cell orientation was mixed. On
      uncoated substrates, the majority of cells oriented to the titanium surface
      features. On fibre-coated glass substrates, cells oriented themselves with
      untreated and plasma-treated fibres and secreted collagen in the same direction
      after 1 week. On uncoated glass substrates, there was no preferred direction of
      collagen orientation. CONCLUSION: Polytetrafluoroethylene nano-fibres induced
      cell and collagen orientation. Surface chemistry appeared only to affect cell
      behaviour at early time points. An implant surface that controls cell orientation
      may also influence the orientation of collagen, providing improved gingival
      support.

PMID- 23134266
TI  - A novel noninvasive method to assess left ventricular -dP/dt using diastolic
      blood pressure and isovolumic relaxation time.
AB  - BACKGROUND: Left ventricular Doppler-derived -dP/dt determined from the
      continuous-wave Doppler spectrum of the mitral regurgitation (MR) jet has been
      shown to be a valuable marker of diastolic function, but requires the presence of
      MR for its assessment. We sought to determine if a novel method of determining 
      dP/dt using the diastolic blood pressure and isovolumic relaxation time (DBP-IVRT
      method) correlates with Doppler-derived -dP/dt using the MR method (Doppler-MR
      method). METHODS: Thirty-three patients with less than severe MR were enrolled. 
      dP/dt was determined using the Doppler-MR method from the continuous-wave Doppler
      spectrum of the MR jet (32 mmHg/time from 3 to 1 m/sec). -dP/dt was also
      determined using the DBP-IVRT method using the following equation: -dP/dt = (DBP 
      LVEDP)/IVRT, where left ventricular end-diastolic pressure (LVEDP) was estimated
      based on tissue Doppler and mitral inflow patterns. RESULTS: Twenty-five patients
      had adequate Doppler waveforms for analysis. The average amount of MR was mild-to
      moderate severity. The mean -dP/dt was 680 +/- 201 mmHg by the Doppler-MR method
      and 681 +/- 237 mmHg by the DBP-IVRT method. There was a significant correlation
      between the 2 methods of determining -dP/dt (Pearson r = 0.574, P = 0.003). The
      Bland-Altman plot revealed almost no bias between the 2 methods; the difference
      in -dP/dt between the 2 techniques was noted to be greater for patients with
      higher -dP/dt, however. CONCLUSION: Diastolic blood pressure and isovolumic
      relaxation time may be used to noninvasively assess diastolic function in
      patients who do not have MR, especially in those with reduced diastolic function.

PMID- 23134267
TI  - Supramolecularly oriented immobilization of proteins using cucurbit[8]uril.
AB  - A supramolecular strategy is used for oriented positioning of proteins on
      surfaces. A viologen-based guest molecule is attached to the surface, while a
      naphthol guest moiety is chemoselectively ligated to a yellow fluorescent
      protein. Cucurbit[8]uril (CB[8]) is used to link the proteins onto surfaces
      through specific charge-transfer interactions between naphthol and viologen
      inside the CB cavity. The assembly process is characterized using fluorescence
      and atomic force microscopy, surface plasmon resonance, IR-reflective absorption,
      and X-ray photoelectron spectroscopy measurements. Two different immobilization
      routes are followed to form patterns of the protein ternary complexes on the
      surfaces. Each immobilization route consists of three steps: (i) attaching the
      viologen to the glass using microcontact chemistry, (ii) blocking, and (iii)
      either incubation or microcontact printing of CB[8] and naphthol guests. In both
      cases uniform and stable fluorescent patterns are fabricated with a high signal
      to-noise ratio. Control experiments confirm that CB[8] serves as a selective
      linking unit to form stable and homogeneous ternary surface-bound complexes as
      envisioned. The attachment of the yellow fluorescent protein complexes is shown
      to be reversible and reusable for assembly as studied using fluorescence
      microscopy.

PMID- 23134268
TI  - Latent tuberculosis infection and active tuberculosis in patients with psoriasis:
      a study on the incidence of tuberculosis and the prevalence of latent
      tuberculosis disease in patients with moderate-severe psoriasis in Spain.
      BIOBADADERM registry.
AB  - INTRODUCTION: The incidence of tuberculosis (TB) or the prevalence of latent
      tuberculosis infection (LTBI) in psoriasis patients has not been described in the
      Spanish population. We carried out a study with the objectives: (i) To describe
      the incidence of TB in patients with psoriasis on systemic treatment in the
      Spanish population; (ii) To determine the prevalence of LTBI in patients who are
      candidates for biological treatment; and (iii) To investigate the level of
      compliance with current recommendations for LTBI and TB screening. METHODS: Data
      were obtained from BIOBADADERM (Spanish registry for systemic biological and non
      biological treatments in psoriasis). An analysis was performed of the exposed
      cohort to determine the prevalence of LTBI and to describe compliance with the
      screening guidelines. RESULTS: A total of 1425 patients were registered in
      BIOBADADERM. They included 793 (56%) patients exposed to biological treatment and
      632 (44%) treated with conventional systemic drug. Overall follow-up was 3720
      person-years. Of the 793, 20.5% (163) were diagnosed with LTBI before starting
      biological treatment. The rate of active TB for the exposed cohort was 145 cases
      * 100,000 patient-years (95% CI 54-389). No case of TB was found in the control
      group. Screening for LTBI was performed in 83% of the exposed sample. CONCLUSION:
      Patients with psoriasis who are exposed to biological treatment appear to be at
      greater risk for tuberculosis. In Spain, up to 20% of patients with psoriasis who
      are candidates for biological therapy have LTBI. There continues to be a
      significant percentage of errors in compliance with clinical guidelines.

PMID- 23134269
TI  - Investigating the photochemical properties of an arenyl dienol.
AB  - Upon irradiation with UV light, an arenyl dienol was transformed into linear and
      angular meta photocycloadducts and ortho derived photoadducts. Extended exposure
      to UV radiation resulted in the formation of other degradation products, which
      shed light on the chemical processes taking place. One of the linear meta
      photocycloadducts was thermally unstable and underwent further thermal and
      photochemical transformation, while the ortho-derived photocycloadducts ring
      opened and eliminated methanol to afford a cyclooctadienone product.

PMID- 23134270
TI  - Ventricular pacing faster than the upper rate in an ICD programmed to the DDD
      mode.

PMID- 23134271
TI  - Non-invasive determination of cellular oxygen consumption as novel cytotoxicity
      assay for nanomaterials.
AB  - Investigating the safety of nanoparticles is essential for many fields of their
      applications, in particular for consumer products, food and medicines. The
      conventional dye and fluorescence-based cytotoxicity assays are limited by the
      interference of such readouts with nanomaterials. This holds in particular when
      nanomaterials have been fluorescently labelled for other purposes, for example,
      confocal microscopy. Moreover, most of these assays are invasive, that is,
      typically involve irreversible changes or destruction of cells and hence only
      allowing one endpoint measurement. Therefore, a non-invasive method for the
      detection of cytotoxicity was developed which is based on the automated online
      monitoring of the oxygen concentration in solution (SensorDish(r) Reader).
      Fluorescently labelled silica nanoparticles with different sizes and surface
      modifications were used as model systems to explore this novel assay. Thereby,
      the SensorDish(r) Reader allows a life documentation of the cellular behaviour
      and clarifies that size, time, concentration and surface modification of
      nanoparticles affect cellular viability.

PMID- 23134272
TI  - Effects of music therapy and guided visual imagery on chemotherapy-induced
      anxiety and nausea-vomiting.
AB  - AIMS AND OBJECTIVES: To reveal the effects of music therapy and visual imagery on
      chemotherapy-induced anxiety and nausea-vomiting. BACKGROUND: Behavioural
      techniques such as music therapy and visual imagery are becoming increasingly
      important in dealing with chemotherapy-induced anxiety, nausea and vomiting.
      DESIGN: The study is an experimental and cross-sectional one and performed on a
      single sample group with the pre-post-test design consisting of 40 individuals.
      The individuals in the sample group comprised both the control and the case group
      of the study. METHODS: To obtain the study data, the following forms were used:
      the Personal Information Form, Spielberger State-Trait Anxiety Inventory, The
      Visual Analogue Scale and Individual Evaluation Form for Nausea and Vomiting
      adapted from The Morrow Assessment of Nausea and Vomiting. RESULTS: In the study,
      the participants' state and trait anxiety levels decreased significantly (p <
      0.05). Music therapy and visual imagery reduced the severity and duration of
      chemotherapy-induced nausea and vomiting significantly (p < 0.05). In our
      research, 40% of the patients did not have anticipatory nausea and 55% of the
      patients did not have anticipatory vomiting during the third chemotherapy cycle
      during which music therapy and guided visual imagery were implemented.
      CONCLUSIONS: It was determined that complementary approaches comprising music
      therapy and visual imagery had positive effects on chemotherapy-induced anxiety,
      nausea and vomiting, which are suffered too often and affect the patients' whole
      lives adversely. RELEVANCE TO CLINICAL PRACTICE: This study is worthy of interest
      as it has revealed that music therapy and visual imagery which have been proven
      to be effective in many health problems in different areas are also important,
      and practical complementary approaches that are effective in getting chemotherapy
      induced anxiety, nausea and vomiting under control.

PMID- 23134273
TI  - Atomic spectroscopy.

PMID- 23134274
TI  - What's in a case?

PMID- 23134275
TI  - A response to Gary Rolfe's 'Cardinal John Henry Newman' and 'the ideal state and
      purpose of a university'.

PMID- 23134276
TI  - A critical discourse analysis of British national newspaper representations of
      the academic level of nurse education: too clever for our own good?
AB  - This critical discourse analysis examines articles about the academic level of
      nurse education that appeared in British national newspapers between 1999 and
      2009. British newspaper journalists regularly attribute problems with recruitment
      into nursing and nursing care to the increasing academic nature of nurse
      education. It is impossible to separate discourse about nurse education from the
      wider nursing discourse. Many journalists laud a traditional and stereotypical
      construct of nurse identity and suggest that increasing nurse education produces
      nurses who are 'too clever to care'. This article argues that whilst nurses lack
      a voice in the National press, they have little input into the construction of
      newspaper discourse about nurse education and subsequently, limited influence on
      resulting public opinion, government policy and the morale of nurses.

PMID- 23134277
TI  - Critical action research applied in clinical placement development in aged care
      facilities.
AB  - The aim of this study was to develop quality clinical placements in residential
      aged care facilities for undergraduate nursing students undertaking their nursing
      practicum topics. The proportion of people aged over 65 years is expected to
      increase steadily from 13% in 2006 to 26% of the total population in Australia in
      2051. However, when demand is increasing for a nursing workforce competent in the
      care of older people, studies have shown that nursing students generally lack
      interest in working with older people. The lack of exposure of nursing students
      to quality clinical placements is one of the key factors contributing to this
      situation. Critical action research built on a partnership between an Australian
      university and five aged care organisations was utilised. A theoretical framework
      informed by Habermas' communicative action theory was utilised to guide the
      action research. Multiple research activities were used to support collaborative
      critical reflection and inform actions throughout the action research. Clinical
      placements in eight residential aged care facilities were developed to support
      179 nursing students across three year-levels to complete their practicum topics.
      Findings were presented in three categories described as structures developed to
      govern clinical placement, learning and teaching in residential aged care
      facilities.

PMID- 23134278
TI  - Trappings of technology: casting palliative care nursing as legal relations.
AB  - Community palliative care nurses in Perth have joined the throng of healthcare
      workers relying on personal digital assistants (PDAs) to store, access and send
      client information in 'real time'. This paper is guided by Heidegger's approach
      to technologies and Habermas' insights into the role of law in administering
      social welfare programs to reveal how new ethical and legal understandings
      regarding patient information add to nursing's professional responsibilities.
      This qualitative research interprets data from interviews with twenty community
      palliative care nurses about clients' legal rights to informational privacy and
      confidentiality. It explores nurses' views of their nursing responsibilities
      regarding clients' legal rights, liability issues, bureaucratic monitoring and
      enforcement procedures. It concludes that nurses and clients are construed as
      legal subjects entrenched in legal relations that have magnified since these
      nurses began using PDAs in 2005/2006.

PMID- 23134279
TI  - Urogenital symptoms and pain history as precursors of vulvodynia: a longitudinal
      study.
AB  - BACKGROUND: We sought to assess vulvodynia incidence and risk factors among those
      with and without premorbid urogenital symptoms. METHODS: Women's Health Registry
      members who completed a baseline assessment in 2004 were sent a 2-year and 4-year
      follow-up survey containing a validated screen for vulvodynia. Subgroup analysis
      of vulvodynia incidence rates was performed, and risk factors associated with
      incidence were assessed. RESULTS: Of 1037 original enrollees, 723 (69.7%)
      completed consecutive surveys (initial and 2-year or initial, 2-year, and 4
      year), 660 of whom did not have current or past vulvodynia at baseline. Of these
      660, 71 (10.8%) first met criteria for vulvodynia within the 4-year period, for
      an annual incidence rate of 3.1% (95% confidence interval [CI] 2.5-4.0). Baseline
      strict controls were less likely to develop criteria for vulvodynia diagnosis
      (annual incidence rate of 1.4%) compared to those with an intermediate phenotype
      (presence of dyspareunia or history of short-term vulvar pain), for whom the
      incidence rate was 5.6% (p<0.001). Risk factors for incident vulvodynia differed
      between these two groups. Among the strict controls, an increased risk was noted
      among younger women (incidence rate ratio) [IRR] 3.6). For those with an
      intermediate phenotype, risk was increased among nonwhite women and those
      reporting pain with or after intercourse (IRR 2.2, 3.4, and 3.1, respectively).
      In both control groups, incident vulvodynia risk increased among those reporting
      urinary burning at enrollment (IRR 4.2 and 2.8 for strict and intermediate
      phenotype controls, respectively). CONCLUSIONS: The annual incidence of
      vulvodynia is substantial (3.1%) and is greater among women reporting a history
      of dyspareunia or vulvar pain that did not meet criteria for vulvodynia compared
      to those without this history, suggesting that generalized urogenital sensitivity
      may be a common underlying mechanism predating the clinical presentation of
      vulvodynia.

PMID- 23134280
TI  - Obstetric-gynecology resident education regarding barrier and over-the-counter
      contraceptives: a national study.
AB  - BACKGROUND: The study was conducted to assess obstetrics-gynecology resident
      knowledge about barrier and over-the-counter (OTC) contraceptives and identify
      strengths and weaknesses in resident education. METHODS: We developed a survey
      for distribution among 50 randomly selected U.S. obstetrics-gynecology residency
      programs. RESULTS: Of 202 respondents, only 57% and 36% of residents reported
      adequate knowledge to counsel patients regarding latex vs. nonlatex condom use,
      respectively. Ninety-six percent knew spermicides were nonprotective against
      sexually transmitted diseases (STDs); however, there was limited knowledge about
      delivery options. Only 17% had ever fit or prescribed a diaphragm, and 30%
      reported knowledge in performing a fitting. Greater than 80% of residents stated
      they received no formal didactics addressing the use of condoms, spermicides, or
      diaphragms. Limited experience regarding Cycle Beads and natural family planning
      was expressed. CONCLUSIONS: Obstetrics-gynecology residents receive little formal
      training about barrier and OTC contraceptive options and seek more education
      because of their awareness of inadequate knowledge.

PMID- 23134281
TI  - Effect of early diabetes on the expression of alpha-1 adrenergic receptors in
      aorta and carotid arteries of Wistar Kyoto and spontaneously hypertensive rats.
AB  - Hypertension and diabetes have been related to noradrenergic system impairment,
      especially to the response mediated by alpha-1 receptors. The aim of this work
      was to investigate possible changes in the expression of alpha-1 adrenergic
      receptors in aorta and carotid arteries of Wistar Kyoto and spontaneously
      hypertensive rats after 4 weeks of the onset of diabetes. Our results suggest
      that early diabetes modifies the expression of alpha-1 adrenergic receptors in
      aorta and carotid arteries of both WKY and SHR strains in a different way. 

PMID- 23134282
TI  - A single amino-acid substitution at lysine 40 of an Arabidopsis thalianaalpha
      tubulin causes extensive cell proliferation and expansion defects.
AB  - Microtubules are highly dynamic cytoskeletal polymers of alpha/beta-tubulin
      heterodimers that undergo multiple post-translational modifications essential for
      various cellular functions in eukaryotes. The lysine 40 (K40) is largely
      conserved in alpha-tubulins in many eukaryote species, and the post-translational
      modification by acetylation at K40 is critical for neuronal development in
      vertebrates. However, the biological function of K40 of alpha-tubulins in plants
      remains unexplored. In this study, we show in Arabidopsis thaliana that
      constitutive expression of mutated forms of alpha-tubulin6 (TUA6) at K40
      (TUA6(K40A) or TUA6(K40Q) ), in which K40 is replaced by alanine or glutamine,
      result in severely reduced plant size. Phenotypic characterization of the
      35S:TUA6(K40A) transgenic plants revealed that both cell proliferation and cell
      expansion were affected. Cytological and biochemical analyses showed that the
      accumulation of alpha- and beta-tubulin proteins was significantly reduced in the
      transgenic plants, and the cortical microtubule arrays were severely disrupted,
      indicating that K40 of the plant alpha-tubulin is critical in maintaining
      microtubule stability. We also constructed 35S:TUA6(K40R) transgenic plants in
      which K40 of the engineered TUA6 protein is replaced by an arginine, and found
      that the 35S:TUA6(K40R) plants were phenotypically indistinguishable from the
      wild-type. Since lysine and arginine are similar in biochemical nature but
      arginine cannot be acetylated, these results suggest a structural importance for
      K40 of alpha-tubulins in cell division and expansion.

PMID- 23134284
TI  - Borneol alleviates oxidative stress via upregulation of Nrf2 and Bcl-2 in SH-SY5Y
      cells.
AB  - CONTEXT: The beta-amyloid (Abeta) peptide aggregation with accompanying oxidative
      stress plays the major role in the pathogenesis of Alzheimer's disease (AD). Some
      natural compounds, including borneol, shed promising light on AD treatment.
      OBJECTIVE: The present study was designed to investigate the antioxidative,
      antiapoptotic effects, and neuroprotection of borneol in human neuroblastoma
      cells (SH-SY5Y). MATERIALS AND METHODS: Oxidative stress was induced by
      administering 50 uM Abeta into SH-SY5Y cells. Neuroprotective effect of
      commercially available borneol was examined by determining cell viability with
      the MTT assay. Intracellular reactive oxygen species (ROS) generation was
      measured using a fluorometer with further examination of heme oxygenase-1 (HO-1)
      and nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) expression. Apoptosis
      was examined by measuring the ratio of B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated
      X protein (Bax). RESULTS: Our data indicated that Abeta-induced cell cytotoxicity
      was inhibited by 100 uM of (-) and (+) borneol treatment. Treatment of borneol
      significantly decreased ROS generation (P < 0.01). The expression of HO-1 and
      nuclear translocation of Nrf2 were increased by Abeta treatment. This nuclear
      translocation of Nrf2 was further increased by administration of borneol.
      Compared with the Abeta treated group, the (+) borneol treated group
      significantly increased Bcl-2 expression with decreased expression of Bax.
      DISCUSSION AND CONCLUSION: Borneol protected SH-SY5Y cells against Abeta-induced
      toxicity, exerted an antioxidative effect and suppressed apoptosis. It increases
      our knowledge about neuroprotective mechanism of borneol, and it is hopeful to be
      a candidate compound for developing therapeutic drug for the prevention and
      treatment of AD and other Abeta-related neurodegenerative diseases.

PMID- 23134285
TI  - Characterization of Shigatoxigenic Escherichia coli strains from Burkina Faso.
AB  - Shigatoxigenic Escherichia coli (STEC) cause serious foodborne infections that
      lead to diarrheal disease and sequelae worldwide. In Burkina Faso, West Africa,
      STEC strains from environmental and human sources have not been isolated and
      characterized before. In this study, 21 STEC strains were isolated from food
      samples of animal origin and human feces using colony hybridization of the Shiga
      toxin gene stx. The STEC strains belonged to 15 different serotypes, including
      O43:H2, O8:H(-), and O2:H2. All strains were positive for stx(1) and 10 also for
      stx(2). The most common stx(1) subtype was stx(1a), and the most common stx(2)
      subtype was stx(2b). In five strains, stx(2) subtypes stx(2a) and/or stx(2c),
      which were previously associated with hemolytic uremic syndrome, were present.
      Some of the strains possessed the gene saa, encoding autoagglutinating adhesin.
      None of the strains possessed the gene eae, encoding intimin. Two STEC strains
      carried also an enterotoxigenic E. coli-associated gene estIa, encoding heat
      stable enterotoxin. The STEC isolated from food in Burkina Faso are potentially
      pathogenic for humans based on the virulence gene combinations that they possess
      and phenotypes that they express.

PMID- 23134286
TI  - Detection of the top six non-O157 Shiga toxin-producing Escherichia coli O groups
      by ELISA.
AB  - There is a growing concern of a public health risk associated with non-O157 Shiga
      toxin-producing Escherichia coli (STEC) since E. coli serogroups O26, O45, O103,
      O111, O121, and O145 are frequently implicated in outbreaks of human illness
      worldwide. Recently, the Food Safety and Inspection Service of the U.S.
      Department of Agriculture declared these six STEC O groups to be adulterants in
      beef. We describe here a rapid, sensitive, and highly specific enzyme-linked
      immunosorbent assay (ELISA) for the detection of these top six non-O157 STEC O
      groups. The assays were tested against 174 reference E. coli O groups, with 60
      clinical isolates belonging to the target O groups and 10 non-E coli strains
      belonging to the family Enterobacteriaceae. Assays for serogroups O103, O111, and
      O121 exhibited 100% specificity, while assays for serogroups O26 and O45 had
      98.2% specificity, and O145 had 99.1% specificity. ELISA conducted using
      artificially inoculated ground beef samples displayed 100% accuracy. The
      sensitivity of the assay was 5*10(5) colony-forming unit (CFU)/mL, with limits of
      detection in the range of 1-10 CFU/25 g of ground beef sample following
      enrichment. The findings of the study suggest that the assay described is simple
      and rapid, and can be employed to detect target STEC O groups in beef and other
      food samples. In addition, the assay provides a conceptual framework that can be
      adapted for the development of similar tests for the rapid detection of other
      serogroups of E. coli.

PMID- 23134287
TI  - Resistance characterization, virulence factors, and ERIC-PCR fingerprinting of
      Aeromonas veronii strains isolated from diseased Trionyx sinensis.
AB  - Aeromonas veronii (AV) is an important pathogen causing severe diseases in
      aquaculture. Fifteen A. veronii strains isolated from diseased Trionyx sinensis
      from four aquafarms was characterized by enterobacterial repetitive intergenic
      consensus-polymerase chain reaction (ERIC-PCR), antibiotic susceptibility
      testing, and identification of virulence factors. A. veronii strains were grouped
      into nine ERIC types with discriminatory ability (D) of 91.43 based on 90%
      similarity. The virulence genes were detected for 73% (aer), 80% (ast), 13%
      (alt), and 40% (act) of the strains, respectively, and five antibiotic resistance
      patterns with D of 0.829 were observed by antibiotic susceptibility testing.
      Furthermore, some AV isolates (AV1, AV2, AV3, and AV4) show the same
      characterization (the same ERIC types, presence of virulence genes in genomes,
      and antibiotics resistance).

PMID- 23134288
TI  - Quantitative and qualitative analysis of naphthenic acids in natural waters
      surrounding the Canadian oil sands industry.
AB  - The Canadian oil sands industry stores toxic oil sands process-affected water
      (OSPW) in large tailings ponds adjacent to the Athabasca River or its
      tributaries, raising concerns over potential seepage. Naphthenic acids (NAs;
      C(n)H(2n-Z)O(2)) are toxic components of OSPW, but are also natural components of
      bitumen and regional groundwaters, and may enter surface waters through
      anthropogenic or natural sources. This study used a selective high-resolution
      mass spectrometry method to examine total NA concentrations and NA profiles in
      OSPW (n = 2), Athabasca River pore water (n = 6, representing groundwater
      contributions) and surface waters (n = 58) from the Lower Athabasca Region. NA
      concentrations in surface water (< 2-80.8 MUg/L) were 100-fold lower than
      previously estimated. Principal components analysis (PCA) distinguished sample
      types based on NA profile, and correlations to water quality variables identified
      two sources of NAs: natural fatty acids, and bitumen-derived NAs. Analysis of NA
      data with water quality variables highlighted two tributaries to the Athabasca
      River-Beaver River and McLean Creek-as possibly receiving OSPW seepage. This
      study is the first comprehensive analysis of NA profiles in surface waters of the
      region, and demonstrates the need for highly selective analytical methods for
      source identification and in monitoring for potential effects of development on
      ambient water quality.

PMID- 23134289
TI  - Synthesis and fungicidal activity of novel 2,5-disubstituted-1,3,4-oxadiazole
      derivatives.
AB  - A novel series of 1,3,4-oxadiazole derivatives containing a 5-phenyl-2-furan
      moiety were synthesized from the intermediates diacylhydrazine 3 and
      acylhydrazone 5 via an efficient approach under microwave irradiation in good
      yields. Their structures were characterized by IR, (1)H NMR, and elemental
      analysis. The antifungal tests indicated that the title compounds showed in vivo
      fungicidal activity against Botrytis cinerea and Rhizoctonia solanii at 500
      MUg/mL obviously. Some tested compounds even had a superiority effect over the
      commercial fungicides 40% Pyrimethanil SC and 3% Validamycin AS. The activity
      between the title compound and their precursors diacylhydrazine 3 and
      acylhydrazone 5 was also compared and discussed.

PMID- 23134290
TI  - Adaptive functioning and its correlates after intestine and liver
      transplantation.
AB  - In this cross-sectional study, we compared levels of adaptive functioning and
      examined potential correlates of adaptive functioning in 18 pediatric intestine
      (ITX) and 22 liver (LTX) recipients transplanted between June 2003 and March
      2009. Family caregivers completed the ABAS-II scale and provided socio
      demographic information regarding recipients' age at transplantation, gender,
      ethnicity, time since transplantation, and caregivers' role, ethnicity,
      education, and family income. Overall adaptive functioning and all three adaptive
      functioning subdomain scores were significantly lower in ITX patients compared
      with LTX patients (p <= 0.04) and compared with the general population normative
      mean (p <= 0.003). Significant correlates of adaptive functioning after abdominal
      transplant included type of transplant procedure (r = -0.4, p = 0.02), gender (r
      = 0.4, p = 0.01), and educational level of caregiver (r = 0.5, p = 0.003) and
      together explained 45% of the variance in overall adaptive functioning. Findings
      provide new information regarding everyday functioning outcomes of ITX patients,
      add to existing data regarding non-medical outcomes for LTX patients, and
      highlight the need for ongoing monitoring and intervention following
      transplantation to enhance outcomes.

PMID- 23134291
TI  - Structure-activity relationships of targeted RuII(eta6-p-cymene) anticancer
      complexes with flavonol-derived ligands.
AB  - RuII(arene) complexes have been shown to be promising anticancer agents, capable
      of overcoming major drawbacks of currently used chemotherapeutics. We have
      synthesized RuII(eta6-arene) compounds carrying bioactive flavonol ligands with
      the aim to obtain multitargeted anticancer agents. To validate this concept,
      studies on the mode of action of the complexes were conducted which indicated
      that they form covalent bonds to DNA, have only minor impact on the cell cycle,
      but inhibit CDK2 and topoisomerase IIalpha in vitro. The cytotoxic activity was
      determined in human cancer cell lines, resulting in very low IC50 values as
      compared to other RuII(arene) complexes and showing a structure-activity
      relationship dependent on the substitution pattern of the flavonol ligand.
      Furthermore, the inhibition of cell growth correlates well with the topoisomerase
      inhibitory activity. Compared to the flavonol ligands, the RuII(eta6-p-cymene)
      complexes are more potent antiproliferative agents, which can be explained by
      potential multitargeted properties.

PMID- 23134295
TI  - PillCam colon capsule endoscopy versus conventional colonoscopy for the detection
      of severity and extent of ulcerative colitis.
AB  - OBJECTIVE: To evaluate PillCam colon capsule endoscopy (PCCE) in detecting the
      severity and extent of active ulcerative colitis (UC), in comparison with
      conventional endoscopy. METHODS: From July 2009 to June 2012, patients with
      confirmed UC were enrolled in this prospective single-center study. After they
      had undergone the PCCE, they received a conventional colonoscopy. The extent of
      mucosal damage and inflammatory lesions during both procedures was recorded for
      comparison. In addition, the regimen of bowel preparation, completion rate,
      colonic cleansing, compliance or adverse events were analyzed. RESULTS: A total
      of 26 patients was consecutively included, among whom one was withdrawn. The
      remaining 25 (nine females and 16 males with a mean age of 44.2 years) completed
      the study. There was significant correlation in the severity (kappa = 0.751, P <
      0.001) and extent (kappa = 0.522, P < 0.001) of UC between the PCCE and
      conventional colonoscopy. In addition, the excellent to good rate of colonic
      cleanliness in PCCE was 80%. There were no remarkable adverse events during the
      study. CONCLUSION: PCCE provides an outstanding performance in the detection of
      the severity and extent of active UC.

PMID- 23134296
TI  - Reply: ICSH recommendations for the measurement of hemoglobin A2.

PMID- 23134297
TI  - Evaluation of cut accuracy and cis cortical damage for tibial plateau leveling
      osteotomy performed with and without aid of a novel saw guide: an in vitro study.
AB  - OBJECTIVES: To compare osteotomy orientation relative to the sagittal and
      transverse planes of the tibia, and cis cortical damage for tibial plateau
      leveling osteotomy (TPLO) performed with the following aids: (1) Synthes TPLO jig
      and saw guide, (2) Slocum TPLO jig with ancillary Kirschner wires (SlocumK), and
      (3) Slocum jig alone. STUDY DESIGN: In vitro study on Synbone((r))  bone models
      and canine cadavers. ANIMALS: Cadaveric pelvic limbs pairs (n = 30). METHODS:
      TPLO was performed on 30 Synbone tibias with either the Slocum jig (n = 10),
      SlocumK (10), or Synthes jig (10). Synbones were analyzed to quantify osteotomy
      inclination, torsion, craniocaudal positioning, and medial cortical bone damage.
      Osteotomies were performed on cadaveric tibias and CT reconstruction used to
      assess the same osteotomy parameters. RESULTS: Significant differences in Synbone
      tibial osteotomy inclination (P < .001), medial cortical bone damage (P < .001)
      and craniocaudal osteotomy position (P < .05) were observed between the Synthes
      and Slocum jigs. CT analysis revealed significant differences in osteotomy
      inclination (P < .001) and torsion (P < .001). The use of the SlocumK resulted in
      osteotomies with minimal torsional malalignment however with high levels of metal
      debris and accelerated blunting of the TPLO blade. CONCLUSION: TPLO osteotomy
      inclination, torsion, and craniocaudal positioning are improved and the degree of
      iatrogenic medial cortical bone damage is minimal with the Synthes TPLO jig
      compared to the Slocum TPLO jig.

PMID- 23134298
TI  - Inverted left atrial appendage masquerading as a cardiac mass.
AB  - An inverted left atrial appendage is a rare phenomenon post cardiac surgery. The
      lesion presents as an additional mass in the left atrium, which would trigger
      unnecessary concerns and frequently, a battery of tests. The lesion can be easily
      diagnosed using echocardiography. We report a case of inverted left atrial
      appendage in a patient post repair of common arterial trunk. Echocardiographic
      pictures and features which help to identify this lesion as well as to
      differentiate it from other possible left atrial mass are described. This article
      aimed to improve the awareness of sonographers toward this rare but possible post
      operative lesion.

PMID- 23134300
TI  - Hydrogen sulfide regulates ethylene-induced stomatal closure in Arabidopsis
      thaliana.
AB  - Hydrogen sulfide (H2 S) is a newly-discovered signaling molecule in plants and
      has caused increasing attention in recent years, but its function in stomatal
      movement is unclear. In plants, H2 S is synthesized via cysteine degradation
      catalyzed by D-/L-cysteine desulfhydrase (D-/L-CDes). AtD-/L-CDes::GUS transgenic
      Arabidopsis thaliana (L.) Heynh. plants were generated and used to investigate
      gene expression patterns, and results showed that AtD-/L-CDes can be expressed in
      guard cells. We also determined the subcellular localization of AtD-/L-CDes using
      transgenic plants of AtD-/L-CDes::GFP, and the results showed that AtD-CDes and
      AtL-CDes are located in the chloroplast and in the cytoplasm, respectively. The
      transcript levels of AtD-CDes and AtL-CDes were affected by the chemicals that
      cause stomatal closure. Among these factors, ACC, a precursor of ethylene, has
      the most significant effect, which indicates that the H2 S generated from D-/L
      CDes may play an important role in ethylene-induced stomatal closure. Meanwhile,
      H2 S synthetic inhibitors significantly inhibited ethylene-induced stomatal
      closure in Arabidopsis. Ethylene treatment caused an increase of H2 S production
      and of AtD-/L-CDes activity in Arabidopsis leaves. AtD-/L-CDes over-expressing
      plants exhibited enhanced induction of stomatal closure compared to the wild-type
      after ethylene treatment; however, the effect was not observed in the Atd-cdes
      and Atl-cdes mutants. In conclusion, our results suggest that the D-/L-CDes
      generated H2 S is involved in the regulation of ethylene-induced stomatal closure
      in Arabidopsis thaliana.

PMID- 23134301
TI  - Intramolecular dehydrogenative coupling of sp2 C-H and sp3 C-H bonds: an
      expeditious route to 2-oxindoles.
AB  - An intramolecular-dehydrogenative-coupling (IDC) using "transition-metal-free"
      oxidation conditions has been achieved to synthesize a variety of 2-oxindoles
      bearing an all-carbon quaternary stereogenic center at the benzylic position. The
      methodology involves a one-pot C-alkylation of beta-N-arylamido esters (3, 6)
      with alkyl halides using potassium tert-butoxide concomitant with a
      dehydrogenative coupling. A radical-mediated pathway has been tentatively
      proposed for the oxidative process.

PMID- 23134302
TI  - Single nucleotide polymorphisms of the bovine VEGF-B gene and their associations
      with growth traits in the Nanyang cattle breed.
AB  - PCR-SSCP and DNA sequencing methods were applied to reveal single nucleotide
      polymorphisms (SNPs) in the bovine VEGF-B gene in 675 samples belonging to three
      native Chinese cattle breeds. We found 3 SNPs and a duplication NC_007330.5: g.
      [782 A>G p. (Gly112 =) (;) 1000-1001dup CT (;) 1079 C>T (;) 2129 G>A p.
      (Arg184Gln)]. We also observed a statistically significant association of the
      polymorphism (1000-1001dup CT) in intron 3 of the VEGF-B gene with the body
      weight of the Nanyang cattle (p < 0.05). This polymorphisms of VEGF-B gene need
      to be verified among a larger cattle population before it can be identified as a
      marker for bovine body weight.

PMID- 23134303
TI  - The fear gene stathmin alleles generated heterosis on feed efficiency parameters
      in Peking ducks.
AB  - Stathmin is an inhibitor of microtubule formation, as highly expressed in the
      lateral nucleus (LA) of the amygdala as well as in the thalamic and cortical
      structures that send information to the LA about the learned and innate fear. So
      we assume that STMN1 genetic variation may also affect the physical activity so
      as to influence the Residual Feed Intake (RFI) of duck. The Single Nucleotide
      Polymorphisms (SNPs) in duck Stathmin gene were screened by sequencing and
      genotyped by restriction endonuclease Msp I, EcoR I, Xho I, Taq I, EcoR II. A
      total of five SNPs (c.187 -15G > A, c.187 -110T > C, c.379 -95G > A, c.379 -318C
      > T, c.426 C > T) were detected in duck STMN1 gene. The c.187 -15G > A is near
      the 3' splice site of intron 2, which has a putative effect on the STMN1 pre-mRNA
      secondary structures. The c.187 -15G > A genotypes had significant effect on RFI
      of Peking drakes (P < 0.01). Individuals with heterozygous genotypes were more
      productive than that with homozygous genotypes, which suggested a molecular
      heterosis in c.187 -15 alleles on RFI. The current study is the first step to
      confirm the relationship between STMN1 gene polymorphisms and RFI. Supplemental
      material is available for this article. Go to the publisher's online edition of
      Animal Biotechnology for a figure of linkage disequilibrium between SNPs and
      table about frequencies of haploype.

PMID- 23134304
TI  - Marker panels for genealogy-based mapping, breed demographics, and inference-of
      ancestry in the dog.
AB  - Short tandem repeat polymorphisms (STRPs) are robust and informative markers for
      a range of genetic applications. STRPs are advantageous in experimental designs
      that derive power from sampling many individuals rather than many loci (e.g.,
      pedigree-based studies, fine-scale mapping, and conservation genetics). STRPs
      have proven useful for vetting samples prior to costly high-density SNP analysis.
      Here we present validated STRPs (n = 1,012) spanning the canine genome (2.1 +/
      1.4 Mb; 2.1 +/-2.1 cM). Standardized design, pre-multiplexing, M13-based dye
      labeling, and selection for loci amenable to semi-automated allele-scoring
      minimize cost and facilitate efficient genotyping. The markers are leveraged from
      the canine linkage map, and thus are backed by genetic data useful for parametric
      multipoint analysis and assessment of empiric coverage. We demonstrate several
      applications with different marker subsets. The complete set provides a genome
      scan for linkage at ~5 cM resolution. A subset of the markers measures molecular
      diversity between domestic and wild canid populations. Another subset reflects
      ancestry within breeds, uncovering hidden stratification and flagging genetic
      outliers prior to SNP genotyping. Thus, the markers described here add
      flexibility and cost effectiveness to several genetic applications in the dog
      that complement genome-wide SNP genotyping studies. Supplemental material is
      available for this article. Go to the publisher's online edition of Animal
      Biotechnology.

PMID- 23134305
TI  - Prokaryotic expression and immunogenicity analysis of yak recombinant myostatin.
AB  - Myostatin (MSTN) is a negative regulator of skeletal muscle growth. The objective
      of the present study was to express yak (Bos grunniens) recombinant MSTN protein
      in E. coli and study its characteristics of immunogenicity. cDNA encoding yak
      MSTN mature peptide was amplified by reverse-transcription PCR, and cloned into
      pET28a(+) vector and expressed in E. coli. The expressed recombinant MSTN was
      purified by affinity chromatography and used to prepare rabbit anti yak MSTN
      antibody. The results showed that yak MSTN mature peptide gene contained 330 bp
      nucleotides coding 109 amino acids. Content of the target protein accounted for
      21% of the total expression products when MSTN-pET28a(+)-BL21(DE3) bacterium was
      incubated in LB medium with 0.1 mM IPTG for 6 hours. The molecular weight of the
      purified yak MSTN recombinant protein was 16.5 kDa, exhibiting excellent
      immunogenicity as shown by ELISA. The obtained recombinant MSTN of yak is
      suitable for further analysis of yak MSTN functions.

PMID- 23134306
TI  - Isolation of a gene encoding a cellulolytic enzyme from swamp buffalo rumen
      metagenomes and its cloning and expression in Escherichia coli.
AB  - Ruminants are capable of hydrolyzing lignocellulosic residues to absorbable
      sugars by virtue of the microbial communities residing in their rumen. However,
      large sections of such microbial communities are not yet culturable using
      conventional laboratory techniques. Therefore in the present study, the
      metagenomic DNA of swamp buffalo (Bubalus bubalis) rumen contents was explored
      using culture-independent techniques. The consensus regions of glycosyl hydrolase
      5 (GH5) family of cellulases were used as primers for PCR amplification. A full
      length metagenomic cellulase gene, Umcel5B29, with a complete open reading frame
      (ORF) of 1611 bp was identified. The similarity search analysis revealed that
      Umcel5B29 is closely related to the cellulases (73% to 98% similarity) of ruminal
      unculturable microorganisms, indicating its phylogenetic origin. Further analysis
      indicated that Umcel5B29 does not contain a carbohydrate binding module (CBM).
      Subsequently, Umcel5B29 was overexpressed in Escherichia coli. The recombinant
      enzyme worked optimally at pH 5.5 and 45 degrees C, a condition similar to the
      buffalo's rumen. However, the enzyme retained more than 70% of its maximal
      activity after incubation at pH 4-7 and more than 50% maximal activity after
      incubation at 30-60 degrees C for 30 min. These characteristics render Umcel5B29
      as a potential candidate for the bio-stoning process of denim.

PMID- 23134307
TI  - Investigation of genetic relationships among Taiwan black pigs and other pig
      breeds in Taiwan based on microsatellite markers.
AB  - The aim of this study was to investigate the genetic relationships between Taiwan
      black pigs (TBP) and other pig breeds by means of 15 fluorescent-labeled
      microsatellite markers. DNA from a total of 299 TBP from eight private farms and
      234 purebred pigs representing six breeds and one synthetic line was used. Among
      the 15 microsatellite loci, polymorphism information content (PIC) values were
      all above 0.500; the numbers of observed alleles were all greater than the
      numbers of effective alleles (10.1 vs. 4.3 in averages). But 13 of the 15
      microsatellite markers significantly deviated from the Hardy-Weinberg equilibrium
      (HWE); moreover, 13 of the 15 tested populations also deviated from the HWE. The
      inbreeding coefficient (F(IS)) indicated that two TBP populations (TBP-3 and TBP
      4) had heterozygote deficiency (P < 0.01). The pair-wise F(ST), representing the
      genetic diversity between the two populations, ranged from 0.0332 to 0.3809.
      Meishan and Taoyuan breeds with black hair were previously considered closely
      related to TBP; however, the result of genetic relationship refuted this
      assumption. In conclusion, TBP is more similar to the European than Chinese
      breeds, and further investigations will need to clarify it more accurately.

PMID- 23134308
TI  - The association of genetic variations in the promoter region of myostatin gene
      with growth traits in Duroc pigs.
AB  - Average daily gain (ADG) and feed efficiency (FE) are important factors for
      assessing productivity in farm animals. Myostatin (MSTN), previously called GDF8,
      is a member of transforming growth factor beta (TGFbeta) superfamily. It is a
      negative regulator for both embryonic development and adult homeostasis of
      skeletal muscle. In this study, the genotypes of MSTN g.435G > A and g.447A > G
      SNPs in Duroc pigs were determined. The 435GG/447AA individually had
      significantly higher ADG (P < 0.01), body weight at 70 d (P < 0.05) and 150 d (P
      < 0.01), and a lower age at 110 kg (P < 0.01) than 435AA/447GG individuals. Dose
      dependent genetic additive effects were found for the negative effects of the
      435A/447 G allele for ADG and body weight on 70 d and 150 d. The 435A/447 G
      allele also increased the age at 110 kg about 1.47 and 4.53% for 1 and 2 copies,
      respectively. The MSTN 435 G/447A allele increased the age at 110 kg about 1.41
      and 4.47% for 1 and 2 copies, respectively. Overall, the two mutated MSTN
      435A/447G allele had negative effects on ADG (P < 0.01), body weight at 70 d (P <
      0.05), and 150 d (P < 0.001) and increased the age at 110 kg (P < 0.001). The
      present study provided evidence that MSTN g.435G > A and g.447A > G affected
      growth in Duroc pigs. The effects of the mutated alleles were additive with the
      maximal effects resulting from two copies of the wild-type allele. Selection for
      the 435 G/447A allele is expected to increase ADG, body weight and decrease the
      age at 110 kg in Duroc pigs and might be used in porcine breeding programs.

PMID- 23134310
TI  - Intentions of nurses and nursing students to tell the whole truth to patients and
      family members.
AB  - AIMS AND OBJECTIVES: To investigate the intentions of nurses and nursing students
      to telling the truth to patients and families, based on the Theory of Planned
      Behavior which examines intention to perform behaviours. BACKGROUND: In recent
      decades, the perception that patients have a moral and legal right to truthful
      and reliable information has become dominant. However, the study of telling the
      truth to non-oncology patients has received scant attention and little is known
      about the intention of nurses and nursing students to tell the truth. DESIGN: A
      cross-sectional design. METHODS: We used a scenario-based questionnaire,
      illustrating eight different situations in which nurses/nursing students are
      asked to tell the truth to a patient or family member regarding a devastating
      disease with which the patient is afflicted. Data were analysed using the Mann
      Whitney U-test and ridge regression. RESULTS: The sample included 150
      participants, 110 registered nurses and 40 third year nursing students, with a
      response rate of 87%. The results show that nurses and nursing students intend to
      tell the whole truth even if this is not easy for them. Nurses more than students
      think that it is important to tell the whole truth and intend to do so. Head
      nurses tend to tell the truth more than staff nurses. For nurses, the components
      of the Theory of Planned Behaviour predicted intention to tell the truth, whereas
      among students subjective norms were the only predictor of intention. CONCLUSION:
      The Theory of Planned Behaviour is a powerful predictor of nurse intention to
      tell the whole truth to patients and their families. Students perceive social
      pressure as the most important incentive of their intention to tell the truth.
      RELEVANCE TO CLINICAL PRACTICE: Nurses and nursing students should receive
      additional training in dealing with various situations involving truth telling.

PMID- 23134311
TI  - Vorticity banding in biphasic polymer blends.
AB  - Pattern formation under the action of flow is a subject of considerable
      scientific interest with applications going from microfluidics to granular
      materials. Here, we present a systematic investigation of shear-induced banding
      in confined biphasic liquid-liquid systems, i.e., formation of alternating
      regions of high and low volume fraction of droplets in a continuous phase (shear
      bands). This phenomenon is investigated in immiscible polymer blends sheared in a
      sliding parallel plate flow cell. Starting from a spatially uniform distribution
      of droplets, the formation of bands aligned along the flow direction is observed,
      eventually leading to an almost complete separation between droplet-rich and
      continuous phase regions. The initial band size is related to the gap dimension;
      the merging of bands and consequent spacing reduction has also been observed for
      long times. Shear banding is only observed when the viscosity of the dispersed
      phase is lower as compared to the continuous phase and in a limited range of the
      applied shear rate. Rheological measurements show that band formation is
      associated with a viscosity decrease with respect to the homogeneous case, thus
      implying that system microstructure is somehow evolving toward reduced viscous
      dissipation under flow.

PMID- 23134312
TI  - Low-potential amperometric enzyme biosensor for xanthine and hypoxanthine.
AB  - The bacterial xanthine dehydrogenase (XDH) from Rhodobacter capsulatus was
      immobilized on an edge-plane pyrolytic graphite (EPG) electrode to construct a
      hypoxanthine/xanthine biosensor that functions at physiological pH. Phenazine
      methosulfate (PMS) was used as a mediator which acts as an artificial electron
      transfer partner for XDH. The enzyme catalyzes the oxidation of hypoxanthine to
      xanthine and also xanthine to uric acid by an oxidative hydroxylation mechanism.
      The present electrochemical biosensor was optimized in terms of applied potential
      and pH. The electrocatalytic oxidation response showed a linear dependence on the
      xanthine concentration ranging from 1.0 * 10(-5) to 1.8 * 10(-3) M with a
      correlation coefficient of 0.994. The modified electrode shows a very low
      detection limit for xanthine of 0.25 nM (signal-to-noise ratio = 3) using
      controlled potential amperometry.

PMID- 23134313
TI  - Low-level laser therapy decreases renal interstitial fibrosis.
AB  - OBJECTIVE: the purpose of this study was to investigate the effect of low-level
      laser therapy (LLLT) on chronic kidney disease (CKD) in a model of unilateral
      ureteral obstruction (UUO). BACKGROUND DATA: Regardless of the etiology, CKD
      involves progressive widespread tissue fibrosis, tubular atrophy, and loss of
      kidney function. This process also occurs in kidney allograft. At present,
      effective therapies for this condition are lacking. We investigated the effects
      of LLLT on the interstitial fibrosis that occurs after experimental UUO in rats.
      METHODS: The occluded kidney of half of the 32 Wistar rats that underwent UUO
      received a single intraoperative dose of LLLT (AlGaAs laser, 780 nm, 22.5
      J/cm(2), 30 mW, 0.75 W/cm(2), 30 sec on each of nine points). After 14 days,
      renal fibrosis was assessed by Sirius red staining under polarized light.
      Immunohistochemical analyses quantitated the renal tissue cells that expressed
      fibroblast (FSP-1) and myofibroblast (alpha-SMA) markers. Reverse transcriptase
      polymerase chain reaction (RT-PCR) was performed to determine the mRNA expression
      of interleukin (IL)-6, monocyte chemotactic protein-1 (MCP-1), transforming
      growth factor (TGF)-beta1 and Smad3. RESULTS: The UUO and LLLT animals had less
      fibrosis than the UUO animals, as well having decreased expression inflammatory
      and pro-fibrotic markers. CONCLUSIONS: For the first time, we showed that LLLT
      had a protective effect regarding renal interstitial fibrosis. It is conceivable
      that by attenuating inflammation, LLLT can prevent tubular activation and
      transdifferentiation, which are the two processes that mainly drive the renal
      fibrosis of the UUO model.

PMID- 23134318
TI  - Folic acid-conjugated LaF3:Yb,Tm@SiO2 nanoprobes for targeting dual-modality
      imaging of upconversion luminescence and X-ray computed tomography.
AB  - Development of multimodal contrast agents for in vivo simultaneous multimodality
      imaging is an emerging interdiscipline that is paving the avenue toward the goal
      of personalized medicine. Herein, folic acid-conjugated silica-modified
      LaF(3):Yb,Tm upconversion nanoparticles (UCNPs@SiO(2)-FA) with high La content in
      a single particle were strategically designed and prepared for simultaneously
      targeting dual-modality imaging of upconversion luminescence (UCL) and X-ray
      computed tomography (CT). LaF(3) UCNPs were synthesized by a novel oleic acid
      (OA)/ionic liquid (IL) two-phase system. Afterward, a folic acid molecule was
      covalently anchored on the surface of UCNPs with a silane coupling agent. The
      UCNPs@SiO(2)-FA exhibits good stability, water dispersibility and solubility, low
      cytotoxicity, good biocompatibility, highly selective targeting, excellent X-ray
      attenuation, and UCL emission under excitation at 980 nm. In vivo UCL and CT
      images of mice show the UCNPs@SiO(2)-FA can be used in targeting dual-modality
      imaging. These results suggest that the as-prepared nanoprobe is a good candidate
      with excellent imaging and targeting ability for targeting dual-modality imaging
      of UCL and CT.

PMID- 23134319
TI  - A first step toward computing all hybridization networks for two rooted binary
      phylogenetic trees.
AB  - Recently, considerable effort has been put into developing fast algorithms to
      reconstruct a rooted phylogenetic network that explains two rooted phylogenetic
      trees and has a minimum number of hybridization vertices. With the standard
      app1235roach to tackle this problem being combinatorial, the reconstructed
      network is rarely unique. From a biological point of view, it is therefore of
      importance to not only compute one network, but all possible networks. In this
      article, we make a first step toward approaching this goal by presenting the
      first algorithm--called ALLMAAFs--that calculates all maximum-acyclic-agreement
      forests for two rooted binary phylogenetic trees on the same set of taxa.

PMID- 23134321
TI  - Hydrophilic and amphiphilic polyethylene glycol-based hydrogels with tunable
      degradability prepared by "click" chemistry.
AB  - Hydrogels with tunable degradability have potential uses in a range of
      applications including drug delivery and tissue scaffolds. A series of
      poly(ethylene glycol) (PEG) hydrogels and amphiphilic PEG-poly(trimethylene
      carbonate ) (PTMC) hydrogels were prepared using copper-catalyzed Huisgen's 1,3
      dipolar cycloaddition, or "click" chemistry as the coupling chemistry. The
      fidelity of the coupling chemistry was confirmed using Fourier transform infrared
      (FTIR) and 1H magic angle spinning (MAS) NMR spectroscopy while thorough swelling
      and degradation studies of the hydrogels were performed to relate network
      structure to the physical properties. The cross-linking efficiency calculated
      using the Flory-Rehner equation varied from 0.90 to 0.99, which indicates that
      the networks are close to "ideal" at a molecular level. However, at the
      microscopic level cryogenic scanning electron microscopy (cryo-SEM) indicated
      that some degree of phase separation was occurring during cross-linking. At 37 
      degrees C and pH 7.4, the degradation rate of the hydrogels increased with
      decreasing cross-link density in the network. Introduction of PTMC as the cross
      linker produced an amphiphilic gel with higher cross-link density and a longer
      degradation time. The degradability of the resultant hydrogels could thus be
      tuned through control of molecular weight and structure of the precursors.

PMID- 23134322
TI  - Utilisation of sFLC assays - how well do we comply with guidelines?
AB  - INTRODUCTION: There is a paucity of data on the utilisation of the serum-free
      light chain (sFLC) and compliance with published guidelines. METHODS: Serum-free
      light chain assays requested at our institute for the diagnosis, prognosis and
      monitoring of plasma cell dyscrasias from July 2008 to March 2010 were compared
      with the International Myeloma Working Group (IMWG) consensus guidelines.
      RESULTS: In total, 1150 assays were performed (4.3 assays per patient, range 1
      20). Eight hundred and forty-four (73%) of these were performed for multiple
      myeloma (MM), 188 (16%) for monoclonal gammopathy of undetermined significance,
      72 (6%) for AL amyloidosis and 46 (4%) for smouldering myeloma. Of these, 49.6%,
      22.9%, 1.4% and 69.6% of the monitoring assays were outside of IMWG
      recommendations, respectively. Of the 419 assays performed outside of guidelines
      for MM patients, 404 (96.4%) were due to monitoring of patients with a measurable
      M protein, while 24 (5.7%) were due to too frequent requesting (<=14 days) with
      15 assays (3.6%) being noncompliant on both grounds. CONCLUSION: Utilisation of
      the sFLC assay shows reasonable adherence to guidelines within our centre. We
      propose to further optimise usage of the test with the help of administrative
      processes and education of clinicians.

PMID- 23134323
TI  - Chrysin: a histone deacetylase 8 inhibitor with anticancer activity and a
      suitable candidate for the standardization of Chinese propolis.
AB  - Chinese propolis (CP) is a natural product collected by honeybees and a health
      food raw material. Previous studies have shown that CP exhibits a broad spectrum
      of biological activities including anticancer, antioxidant, antibacterial, anti
      inflammatory, and antiviral activities. The focuses of the present study were the
      standardization of CP and the possible mechanisms of its active anticancer
      ingredients. Nine samples of CP were collected from different locations in China.
      Analyses of the CP samples revealed that all 9 had similar chemical compositions.
      Parameters analyzed included the CP extract dry weight, total phenolic content,
      and DPPH free radical scavenging activities. The active anticancer ingredient was
      isolated, characterized against human MDA-MB-231 breast cancer cells, and
      identified as chyrsin, a known potent anticancer compound. Chrysin is present at
      high levels in all 9 of the CP samples, constituting approximately 2.52% to 6.38%
      of the CP extracts. However, caffeic acid phenethyl ester (CAPE), another potent
      active ingredient is present in low levels in 9 samples of CP, constituting
      approximately 0.08% to 1.71% of the CP extracts. Results from analyses of
      enzymatic activity indicated that chrysin is a histone deacetylase inhibitor
      (HDACi) and that it markedly inhibited HDAC8 enzymatic activity (EC(50) = 40.2
      MUM). In vitro analyses demonstrated that chrysin significantly suppressed cell
      growth and induced differentiation in MDA-MB-231 cells. In a xenograft animal
      model (MDA-MB-231 cells), orally administered chrysin (90 mg/kg/day)
      significantly inhibited tumor growth. Despite the geographical diversity of the 9
      samples' botanical origins, their chemical compositions and several analyzed
      parameters were similar, suggesting that CP is standardized, with chrysin being
      the major active ingredient. Overall, in vitro and in vivo data indicated that
      chrysin is an HDAC8 inhibitor, which can significantly inhibit tumor growth. Data
      also suggested that chrysin might represent a suitable candidate for
      standardization of CP.

PMID- 23134324
TI  - Three new triterpenoid saponins from Ilex pubescens.
AB  - Three new triterpene saponins, ilexsaponins D-F (1-3), were isolated from the
      roots of Ilex pubescens. Their structures were elucidated as 3-O-beta-D
      glucopyranosyl(1 -> 3)-alpha-L-arabinopyranosyl urs-12,18-diene-24,28-dioic acid
      28-O-beta-D-glucopyranoside (1), 3-O-beta-D-glucopyranosyl(1 -> 3)-alpha-L
      arabinopyranosyl urs-12,18-diene-24,28-dioic acid (2), and 3-O-beta-D
      glucopyranosyl(1 -> 3)-alpha-L-arabinoyranosyl-30-hydroxyurs-12,19-diene-24,28
      dioic acid 28-O-beta-D-glucopyranoside (3) on the basis of the chemical and
      spectroscopic evidence.

PMID- 23134325
TI  - An apparent case of undiagnosed donor Kawasaki disease manifesting as coronary
      artery aneurysm in a pediatric heart transplant recipient.
AB  - We present a case of coronary ectasia and LAD coronary artery aneurysm with
      angiographic characteristics of Kawasaki disease in a three-yr-old girl two-yr
      status post-orthotopic heart transplant. Coronary anomalies were noted during
      initial screening coronary angiography two yr after transplant. Subsequent review
      of the donor echocardiogram revealed that the LMCA had been mildly dilated prior
      to transplant. In the absence of any symptoms consistent with Kawasaki disease in
      the transplant recipient, this appears to be a case of Kawasaki disease in the
      organ donor manifesting with coronary anomalies in the transplant recipient. The
      patient has done well clinically, and repeat coronary angiography has revealed
      partial regression of coronary anomalies. Given multiple reports in the
      literature of persistent abnormalities of coronary artery morphology and function
      after Kawasaki disease, close monitoring is warranted, with consideration of
      potential coronary protective medical therapies.

PMID- 23134326
TI  - Risk-managed approach for routing petroleum pipelines: Keystone XL pipeline,
      Nebraska.
AB  - TransCanada's proposed international crude oil pipeline route over sensitive,
      relatively pristine, subirrigated land underlain by the Ogallala aquifer led to
      increased scrutiny and eventual rejection of the Keystone XL pipeline. Pipeline
      routing could be made much more acceptable by adopting risk-managed routes that
      lessen the potential to adversely impact high-quality groundwater and, should a
      release occur, decrease the longevity of hazardous groundwater contaminants.
      Threats to water quality are taken quite seriously in states like Nebraska where
      85% of the population depend on groundwater for potable water.

PMID- 23134327
TI  - Effect of recombinant Lactobacillus casei expressing interleukin-10 in dextran
      sulfate sodium-induced colitis mice.
AB  - OBJECTIVE: To study the effect of recombinant Lactobacillus casei (L.casei)
      expressing interleukin (IL)-10 combined with 5-aminosalicylic acid (5-ASA) in
      dextran sulfate sodium (DSS)-induced colitis mice. METHODS: Recombinant L. casei
      CECT 5276, which can secrete IL-10, was constructed. The length of colon tissue,
      disease activity index (DAI) and histological score (HS) of the mice were
      determined to evaluate the modeling and the effectiveness of L. casei. Real-time
      polymerase chain reaction (PCR), Western blot and ELISA were used to determine
      the levels of nuclear factor kappa-light-chain-enhancer of activated B cells (NF
      kappaB), peroxisome proliferator-activated receptor (PPAR)-gamma, interferon
      (IFN)-gamma, transforming growth factor (TGF)-beta and IL-10. RESULTS:
      Recombinant L. casei expressing IL-10 combined with 5-ASA was more effective than
      L. casei with 5-ASA. Among the three different concentrations of the recombinant
      L. casei, the highest concentration group (2 * 10(9) colony-forming units/mL) had
      the best effectiveness. CONCLUSIONS: Recombinant L. casei combined with 5-ASA is
      effective in the treatment of DSS-induced colitis. The possible mechanism might
      be the blocking of the excessive activation of NF-kappaB pathway, thus
      suppressing the release of inflammation-related factors.

PMID- 23134328
TI  - Influence of age on tooth autotransplantation with complete root formation.
AB  - The aim of this study was to investigate risk factors with age in the long-term
      prognosis of autotransplantation of teeth with complete root formation at dental
      clinics. Participating dentists were asked to provide information on
      transplantations they had undertaken from 1 January 1990 to 31 December 2010.
      Data on a total of 708 teeth from 637 patients were collected. The data were
      screened to exclude patients who were under 25 or 70 years of age and over, those
      who were smokers or whose smoking habits were unknown, those whose transplanted
      teeth had incomplete root formation or multiple roots and those with fewer than
      25 present teeth post-operation. The participants in this study were 71 men (74
      teeth) and 100 women (107 teeth) ranging from 25 to 69 years of age. Third molars
      were used as donor teeth in 89.0% of the cases. The participants were divided
      into three age groups of 25-39, 40-54 and 55-69. Survival analysis was conducted
      using the Kaplan-Meier method, and a log-rank test revealed that there were no
      significant differences in age groups for men or women. Cox regression analysis
      indicated that the survival of transplanted teeth was not influenced by age.
      However, although not statistically significant, the clinical success rate was
      lower in the 55-69-year-old group than that in the younger groups. These results
      indicate that if suitable donor teeth are available and the conditions are right,
      autotransplantation is a viable treatment for missing teeth regardless of the age
      of the patient.

PMID- 23134329
TI  - Corticosteroids for pneumonia: are we there yet?

PMID- 23134330
TI  - Interim positron emission tomography in early stage Hodgkin lymphoma: is there
      evidence for its prognostic and predictive value in patients treated with
      standard combined modality treatment?

PMID- 23134331
TI  - Cultural adaptation and psychometric properties of the family questionnaire in a
      Brazilian sample of relatives of schizophrenia outpatients.
AB  - AIMS AND OBJECTIVES: To evaluate the internal reliability and validity of the
      Brazilian Portuguese version of the Family Questionnaire among families of
      schizophrenia outpatients. BACKGROUND: The main studies about the family
      environment of schizophrenia patients are related to the concept of Expressed
      Emotion. There is currently no instrument to evaluate this concept in Brazil that
      is easily applicable and comparable with studies from other countries. DESIGN:
      Methodological and cross-sectional research design. METHOD: A convenience sample
      of 130 relatives of schizophrenia outpatients was selected. The translation and
      cultural adaptation of the instrument involved experts in mental health and
      experts in the German language and included back translation, semantic evaluation
      of items and pretesting of the instrument with 30 relatives of schizophrenia
      outpatients. The psychometric properties of the instrument were studied with
      another 100 relatives, which fulfilled the requirements for the Brazilian
      Portuguese version of the instrument. The psychometric properties of the
      instrument were assessed by construct validity (using an analysis of its key
      components, comparisons between distinct groups-convergent validity with the
      Antonovsky's Sense of Coherence Scale) and reliability (checking the internal
      consistency of its items and its test-retest reproducibility). RESULTS: The
      analysis of main components confirmed dimensionality patterns that were
      comparable between the original and adapted versions. In two domains of the
      instrument, critical comments and emotional over-involvement had moderate and
      significant correlations, respectively, with Antonovsky's Sense of Coherence
      Scale, appropriate values of Cronbach's alpha and strong and significant
      correlations, respectively, in test-retest reproducibility. We observed
      significant differences between distinct groups of parents in the category of
      emotional over-involvement. CONCLUSION: We conclude that the Portuguese-adapted
      version of the Family Questionnaire is valid and reliable for the study sample.
      RELEVANCE TO CLINICAL PRACTICE: This study provided evidence that the Family
      Questionnaire is a reliable and valid instrument for assessing expressed emotion.
      It is easy and practical to use and is acceptable for use in a Brazilian cultural
      population.

PMID- 23134332
TI  - Demonstration of right ventricular volume assessment by three-dimensional speckle
      tracking echocardiography in an infant with surgically palliated hypoplastic left
      heart syndrome (a case from the MAGYAR-Path Study).

PMID- 23134334
TI  - Current trends in microbial diagnostics based on mass spectrometry.

PMID- 23134335
TI  - Acetylcholinesterase inhibitors from the leaves of Macaranga kurzii.
AB  - Bioassay-guided fractionation of an extract of leaves of Macaranga kurzii yielded
      four new compounds, a stilbene (furanokurzin, 1) and three flavonoids (macakurzin
      A-C, 2-4). Nine known compounds were also isolated (5-13). Their structures were
      determined by spectroscopic analyses including MS and 2D NMR. The isolates were
      all evaluated for acetylcholinesterase inhibitory activity. Compound 6 (trans-3,5
      dimethoxystilbene) exhibited the greatest activity (IC50 9 MUM). Cytotoxic
      evaluation against KB cells showed that compound 7 had an IC50 of 4 MUM, followed
      by 11 (IC50 10 MUM) and 3 (IC50 13 MUM). 

PMID- 23134336
TI  - Photophysics and photochemistry of thymine deoxy-dinucleotide in water: a PCM/TD
      DFT quantum mechanical study.
AB  - We here report a fully quantum mechanical study of the main photochemical and
      photophysical decay routes in aqueous solution of thymine deoxy-dinucleotide
      (TpT(-) and TpTNa) and of its analogue locked in C3-endo puckering,
      characterizing five different representative backbone conformers and discussing
      the chemical physical effects modulating the yield of the different
      photoproducts. Our approach is based on time-dependent DFT calculations, using
      the last generation M052X functional, whereas solvent effects are included by
      means of the polarizable continuum model. Especially when at least one of the
      sugars adopts C3-endo puckering, a barrierless path on the bright pipi* excitons
      leads to the S(1)/S(0) crossing region corresponding to the formation of
      cyclobutane pyrimidine dimer. Charge transfer excited states involving the
      transfer of an electron from the 5' Thy toward the 3' Thy are involved in the
      formation of the oxetane intermediate in the path leading to 6-4 pyrimidine
      pyrimidinone adducts. A non-negligible energy barrier is associated with this
      latter pathway, which is possible only when one of the two nucleotides adopts C2
      endo puckering. Monomer-like decay pathways, involving pipi* or npi* excited
      states localized on a single base, are shown to be operative also for loosely
      stacked bases.

PMID- 23134337
TI  - Genetic analyses of Xanthomonas axonopodis pv. dieffenbachiae strains reveal
      distinct phylogenetic groups.
AB  - A comprehensive analysis of 175 Xanthomonas axonopodis pv. dieffenbachiae strains
      isolated from 10 Araceae hosts was done to identify pathogen variation. The
      strains were subjected to repetitive extragenic palindromic sequence polymerase
      chain reaction and four major phylogenetic clusters were generated. A subset of
      40 strains isolated from Anthurium, Dieffenbachia, and Syngonium was further
      defined by amplified fragment length polymorphism and fatty acid methyl ester
      analysis and the same four phylogenetic clusters were observed. Comparison of
      representative strains in the first three clusters using DNA-DNA hybridization
      and multilocus sequence analysis supports the previous reclassification of
      strains in cluster I, including the X. axonopodis pv. dieffenbachiae pathovar
      reference strain (LMG695), to X. citri. Our research findings indicate that
      strains in cluster I, isolated primarily from anthurium, probably represent an
      undescribed pathovar. Other phylogenetic subclusters consisting primarily of
      strains isolated from xanthosoma and philodendron in clusters III and IV,
      respectively, may yet represent other undescribed species or pathovars of
      Xanthomonas.

PMID- 23134338
TI  - Clinical practice guideline for an integrated approach to comorbidity in patients
      with psoriasis.
AB  - BACKGROUND: The relationship between psoriasis and associated diseases has drawn
      particular interest in recent years. To provide appropriate management of
      psoriasis from an early stage, it is necessary to include prompt diagnosis of
      concomitant disease and to prevent and treat any comorbidity found. Such an
      integrated approach also serves to ensure that the drugs used to treat associated
      diseases do not interfere with the management of psoriasis, and vice versa.
      OBJECTIVE: To provide the dermatologist a guide focuses specifically on the
      diagnosis and management of the diseases most often found in patients with
      psoriasis. METHODS: The selection of the diseases, and corresponding supporting
      research, to be included was based on a systematic review of the literature. The
      recommendations on diagnostic criteria are based on the main clinical practice
      guidelines for each of the diseases discussed as well as on the recommendations
      of a clinical expert advisory group. The information regarding the repercussions
      of psoriasis treatments on associated comorbid diseases was obtained from the
      summary of product characteristics of each drug. In turn, the statements
      concerning the impact of the associated diseases, and their treatment, on
      psoriasis are based on the review of the literature. RESULTS: This guide is a
      precise, easy-to-use tool for systematizing the diagnosis of comorbidity in
      patients with psoriasis and facilitate decision making regarding referral and
      treatment of patients diagnosed with an associated disease. CONCLUSION: The
      application of this guide not only will benefit psoriasis patients' health and
      quality of life but it will also optimize available resources.

PMID- 23134340
TI  - Adult neural stem cells: an endogenous tool to repair brain injury?
AB  - Research on stem cells has developed as one of the most promising areas of
      neurobiology. In the beginning of the 1990s, neurogenesis in the adult brain was
      indisputably accepted, eliciting great research efforts. Neural stem cells in the
      adult mammalian brain are located in the 'neurogenic' areas of the subventricular
      and subgranular zones. Nevertheless, many reports indicate that they subsist in
      other regions of the adult brain. Adult neural stem cells have arisen
      considerable interest as these studies can be useful to develop new methods to
      replace damaged neurons and treat severe neurological diseases such as
      neurodegeneration, stroke or spinal cord lesions. In particular, a promising
      field is aimed at stimulating or trigger a self-repair system in the diseased
      brain driven by its own stem cell population. Here, we will revise the latest
      findings on the characterization of active and quiescent adult neural stem cells
      in the main regions of neurogenesis and the factors necessary to maintain their
      active and resting states, stimulate migration and homing in diseased areas,
      hoping to outline the emerging knowledge for the promotion of regeneration in the
      brain based on endogenous stem cells.

PMID- 23134339
TI  - Effects of different types of acute and chronic (training) exercise on glycaemic
      control in type 1 diabetes mellitus: a meta-analysis.
AB  - OBJECTIVE: Exercise has been accepted and generally recommended for the
      management of type 1 diabetes mellitus (T1D) and for improving the overall
      quality of life in affected individuals. This meta-analysis was conducted to
      determine the overall effects of exercise (acute bouts of exercise and chronic
      exercise [or training]) on acute and chronic glycaemic control in patients with
      T1D, the effects of different types of exercise on glycaemic control and which
      conditions are required to obtain these positive effects. METHODS: PubMed, ISI
      Web of Knowledge and SPORTDiscusTM were consulted to identify studies on T1D and
      exercise. Cohen's d statistics were used for calculating mean effect sizes (ES)
      as follows: small d = 0.3, medium d = 0.5 and large d = 0.8. Ninety-five percent
      confidence intervals (95% CIs) were used to establish the significance of our
      findings. RESULTS: From a total of 937 studies, 33 that met the inclusion
      criteria were selected. Nine studies were used to calculate the ES of a single
      bout of aerobic exercise; 13 studies to calculate the ES of aerobic training; 2
      studies to calculate the ES of strength training; 4 studies to calculate the ES
      of combined (aerobic and strength) training and 6 studies to calculate the ES of
      high-intensity exercise (HIE) and training. ES for exercise on acute glycaemic
      control were large, while they were small for chronic glycaemic control. Aerobic
      exercise, resistance exercise, mixed exercise (aerobic combined with resistance
      training) and HIE acutely decreased blood glucose levels. To prevent late-onset
      hypoglycaemic episodes, the use of single bouts of sprints into an aerobic
      exercise can be recommended. This meta-analysis also showed that a regular
      exercise training programme has a significant effect on acute and chronic
      glycaemic control, although not all exercise forms showed significant results.
      Specifically, aerobic training is a favourable tool for decreasing chronic
      glycaemic control, while resistance training, mixed and HIE did not significantly
      improve chronic glycaemic control. Although, this meta-analysis showed there was
      a tendency for improvement in glycaemic control due to resistance training or
      resistance training combined with endurance training, there were not enough
      studies and/or subjects to confirm this statistically. CONCLUSIONS: Based on this
      meta-analysis, we can conclude that the addition of brief bouts of high
      intensity, sprint-type exercise to aerobic exercise can minimize the risk of
      sustaining a hypoglycaemic episode. We can also conclude that only regular
      aerobic training will improve the glycated haemoglobin level of a patient with
      T1D.

PMID- 23134341
TI  - DNA-binding regulates site-specific ubiquitination of IRF-1.
AB  - Understanding the determinants for site-specific ubiquitination by E3 ligase
      components of the ubiquitin machinery is proving to be a challenge. In the
      present study we investigate the role of an E3 ligase docking site (Mf2 domain)
      in an intrinsically disordered domain of IRF-1 [IFN (interferon) regulatory
      factor-1], a short-lived IFNgamma-regulated transcription factor, in
      ubiquitination of the protein. Ubiquitin modification of full-length IRF-1 by E3
      ligases such as CHIP [C-terminus of the Hsc (heat-shock cognate) 70-interacting
      protein] and MDM2 (murine double minute 2), which dock to the Mf2 domain, was
      specific for lysine residues found predominantly in loop structures that extend
      from the DNA-binding domain, whereas no modification was detected in the more
      conformationally flexible C-terminal half of the protein. The E3 docking site was
      not available when IRF-1 was in its DNA-bound conformation and cognate DNA
      binding sequences strongly suppressed ubiquitination, highlighting a strict
      relationship between ligase binding and site-specific modification at residues in
      the DNA-binding domain. Hyperubiquitination of a non-DNA-binding mutant supports
      a mechanism where an active DNA-bound pool of IRF-1 is protected from
      polyubiquitination and degradation.

PMID- 23134342
TI  - The bridging force between colloidal particles in a polyelectrolyte solution.
AB  - The presence of a polyelectrolyte in a colloidal dispersion affects the
      interaction between colloidal particles through electrostatic and bridging
      interactions. In this paper, using a self-consistent field approach, a simple
      theory is developed which allows for the calculation of the bridging force
      between two plates and two colloidal particles. The present approach differs from
      the previous ones, since the contribution of the plate-solution interfacial
      tension to the free energy is taken into account in the calculation. The
      interfacial tension between solvent and plate depends on the nature of the
      particles and the concentration of the segments of the polymer at the surface.
      The surface-segment interaction has a significant effect on the segment
      concentration profile. When the segment-surface interaction is repulsive, the
      bridging force is weak because few polyelectrolyte chains are adsorbed onto the
      surface. When the segment-surface interaction is attractive, various segment
      concentration profiles could be identified. Depending upon the concentration of
      polyelectrolyte, the electrostatic plus bridging forces can be attractive or
      repulsive. The bridging force between two plates which is attractive has a longer
      range than the van der Waals interaction.

PMID- 23134343
TI  - Syntheses, structures, and magnetic properties of a novel mer
      [(bbp)Fe(III)(CN)3](2-) building block (bbp: bis(2-benzimidazolyl)pyridine
      dianion) and its related heterobimetallic Fe(III)-Ni(II) complexes.
AB  - A new symmetrical tricyanide building block mer-[Fe(bbp)(CN)3](2-) [1; bbp =
      bis(2-benzimidazolyl)pyridine dianion] has been prepared and structurally and
      magnetically characterized. It forms a new low-spin meridionally capped
      {Fe(III)L(CN)3} fragment with the tridentate bbp ligand. The reaction of 1 with
      Ni(II) salts in the presence of various ancillary ligands affords several new
      cyanido-bridged complexes: a trinuclear complex
      {[Ni(ntb)(MeOH)]2[Fe(bbp)(CN)3][ClO4]2}.2MeOH (2), a tetranuclear compound
      {[Ni(tren)]2[Fe(bbp)(CN)3]2}.7MeOH (3), and a one-dimensional heterobimetallic
      system: {[Ni(dpd)2]2[Fe(bbp)(CN)3]2}.9MeOH.3H2O (4) [ntb = tris(2
      benzimidazolylmethyl)amine, tren = tris(2-aminoethyl)amine, and dpd = 2,2
      dimethyl-1,3-propanediamine]. The structural data shows that 2 is a linear
      complex in which a central Fe(III) ion links two adjacent Ni(II) ions via axial
      cyanides, while 3 is a molecular square that contains cyanido-bridged Ni(II) and
      Fe(III) ions at alternate corners. Complex 4 is a one-dimensional system that is
      composed of alternating cyanido-bridged Ni(II) and Fe(III) centers. Compounds 2-4
      display extensive hydrogen bonding and moderately strong pi-pi stacking
      interactions in the solid state. Magnetic studies show that ferromagnetic
      exchange is operative within the Fe(III)LS(MU-CN)Ni(II) units of 2-4. 

PMID- 23134344
TI  - Overexpression of signal transducer and activator of transcription (STAT-3 and
      STAT-5) transcription factors and alteration of suppressor of cytokine signaling
      (SOCS-1) protein in prostate cancer.
AB  - BACKGROUND: Prostate cancer is a leading cause of mortality in men worldwide
      especially in developing countries like India. The molecular mechanisms of the
      oncogenic signaling pathway(s) that are involved in prostate carcinogenesis play
      a crucial role in disease progression and persistence. There is an important role
      of signal transducer and activator of transcriptions (STATs) particularly STAT-3
      and STAT-5 and its negative regulator suppressor of cytokine signaling-1 (SOCS
      1). METHODS: In the present study, the expression and localization of STAT and
      SOCS-1 proteins in prostate cancer by immunohistochemistry in a total of 150
      formalin-fixed, paraffin-embedded human prostate tissues of different grade
      obtained by radical prostatectomies or transurethral resection. RESULTS: A
      significantly strong STAT-3 expression pattern in 68% (65/95) prostate cancer
      cases as compared to 12% (5/55) in benign prostatic hyperplasia (BPH) controls (P
      < 0.001) was observed. Interestingly the SOCS-1 expression was found to be
      significantly elevated in prostate cancer cases (P < 0.001). CONCLUSIONS: The
      present study demonstrates overexpression of STAT-3 and STAT-5 proteins and a
      contrasting role of SOCS-1 in prostate cancer. These results suggest a critical
      association between altered expression of STAT-3 and STAT-5 with SOCS-1 and
      indicate its potential role as a negative regulator independent of JAK-STAT
      pathway in tumorigenic transformation of prostate tissue. The results of the
      present report focuses on the fundamental differences in major oncogenic
      signaling cascades between benign and malignant form of prostate tissue that
      plays a crucial role in prostate cancer biology.

PMID- 23134345
TI  - Magnesium affects the cytokine secretion of CD4+ T lymphocytes in acute asthma.
AB  - INTRODUCTION: Magnesium (Mg) administration has been shown to promote
      bronchodilation and to improve lung function in asthma. It also plays an
      additional role in modulating the immune responses. This study was initiated to
      explore if Mg supplementation could affect the secretion of cytokines in acute
      asthmatic CD4+ T cells. METHODS: Total serum Mg concentrations of the acute
      asthmatic patients and healthy controls were determined. CD4+ T cells were
      isolated from the blood of the acute asthmatic patients. They were cultured in
      various concentrations of Mg-supplemented (0.8, 5, 10, 15, and 20 mmol/l) medium.
      Cytokine (IL-5, IL-13, and IFN-gamma) levels were determined by Enzyme-Linked
      Immunosorbnent Assay (ELISA). RESULTS: Serum Mg concentration was lower in the
      acute asthmatic patients than that in the healthy controls (p < .05). The
      secretion of IL-5 and IL-13 was decreased, while the acute asthmatic CD4+ T cells
      were cultured in 10 and 15 mmol/l Mg-supplemented medium, respectively, as
      compared to the 0.8 mmol/l Mg group (p < .05). The secretion of IFN-gamma
      increased in the 10 mmol/l Mg group (p < .05). CONCLUSION: Mg supplementation was
      able to modulate the immune responses of acute asthmatic CD4+ T cells and
      decrease the secretion of type 2 CD4+ T lymphocytes cytokines.

PMID- 23134346
TI  - Reaching out to our youth about organ donation.

PMID- 23134347
TI  - New iridoid glycoside from Gratiola officinalis.
AB  - A new iridoid glycoside, 1beta,6beta-di-O-trans-cinnamoyl-9-O-beta-D
      glucopyranosyl-3-iridene-5beta-ol (1), along with four known compounds loliolide
      (2), beta-sitosterol-3-O-beta-D-glucopyranoside (3), betulinic acid (4), and beta
      amyrin (5), was isolated from the aerial parts of Gratiola officinalis L. The
      structure of the new compound was deduced on the basis of 1D 1H and 13C NMR and
      2D HMQC, HMBC, and COSY experiments, and mass spectrometric techniques (EI-MS and
      HR-EI-MS). The relative configuration of 1 was assigned by comparative analysis
      of the NMR spectral data with known analogs, together with NOESY experiments.

PMID- 23134348
TI  - Homozygosity mapping identifies genetic defects in four consanguineous families
      with retinal dystrophy from Pakistan.

PMID- 23134349
TI  - Silk fibroin/hyaluronic acid 3D matrices for cartilage tissue engineering.
AB  - In spite of commercially available products, the complete and sustained repair of
      damaged articular cartilage still presents various challenges. Among biomaterials
      proposed for cartilage repair, silk fibroin (SF) has been recently proposed as a
      material template for porous scaffolds cultured with chondrocytes and
      investigated in static and dynamic conditions. In addition to fibroin-based
      constructs, literature has reported that the combination of hyaluronic acid (HA)
      with other scaffold materials can protect the chondral phenotype and the cells in
      vitro response to the scaffold. In this study, the effect of the addition of HA
      on the physical properties of SF sponges, with and without cross-linking with
      genipin, was investigated. Salt-leached scaffolds were characterized in terms of
      morphology and structural and physical properties, as well as mechanical
      performance. Un-cross-linked sponges resulted in the physical separation of
      highly hydrophilic HA from the SF, while cross-linking prevented this phenomenon,
      resulting in a homogeneous blend. The presence of HA also influenced fibroin
      crystallinity and tended to decrease the cross-linking degree of the scaffolds
      when compared to the pure SF material.

PMID- 23134352
TI  - Novel xylanase from a holstein cattle rumen metagenomic library and its
      application in xylooligosaccharide and ferulic Acid production from wheat straw.
AB  - A novel gene fragment containing a xylanase was identified from a Holstein cattle
      rumen metagenomic library. The novel xylanase (Xyln-SH1) belonged to the
      glycoside hydrolase family 10 (GH10) and exhibited a maximum of 44% identity to
      the glycoside hydrolase from  Clostridium thermocellum  ATCC 27405. Xyln-SH1 was
      heterologously expressed, purified, and characterized. A high level of activity
      was obtained under the optimum conditions of pH 6.5 and 40  degrees C. A
      substrate utilization study indicated that Xyln-SH1 was cellulase-free and
      strictly specific to xylan from softwood. The synergistic effects of Xyln-SH1 and
      feruloyl esterase (FAE-SH1) were observed for the release of xylooligosaccharides
      (XOS) and ferulic acid (FA) from wheat straw. In addition, a high dose of Xyln
      SH1 alone was observed to improve the release of FA from wheat straw. These
      features suggest that this enzyme has substantial potential to improve biomass
      degradation and industrial applications.

PMID- 23134353
TI  - L539 fs/47, a truncated mutation of human ether-a-go-go-related gene (hERG),
      decreases hERG ion channel currents in HEK 293 cells.
AB  - Mutations in the human ether-a-go-go-related gene (hERG) are responsible for
      congenital Type 2 long QT syndrome (LQT2). Previously, we reported a truncated
      mutation of hERG in a Chinese family with LQT2, namely L539 fs/47, which is
      composed of a 19 bp deletion mutation and an A1692G polymorphism. This mutation
      was found to cause an LQT2 phenotype. The aim of the present study was to
      investigate the functional role of L539 fs/47 at the cellular level and its
      potential contribution to the loss of function of hERG channels. The function of
      the truncated mutation L539 fs/47 was evaluated by constructing a mutated
      plasmid, transfection of the mutated cDNA into HEK 293 cells and subsequent patch
      clamp, western blotting and immunostaining experiments. Homologous expression of
      L539 fs/47 in HEK 293 cells produced a non-functional protein that was detected
      in cell membranes. When L539 fs/47 was expressed simultaneously with wild-type
      hERG, it suppressed wild-type hERG currents in a dose-dependent manner and
      changed the gating properties of the channel. Although L539 fs/47 hERG proteins
      were detected on plasma membranes, they failed to generate hERG currents. In
      general, L539 fs/47 dose-dependently decreases hERG ion channel currents and
      suppresses the function of wild-type channels function. This may explain, in
      part, the clinical manifestations of LQT2 in the family with this mutation.

PMID- 23134354
TI  - Evaluation of fragmented red cell (FRC) counting using Sysmex XE-5000 - does
      hypochromia play a role?
AB  - INTRODUCTION: Schistocytes are major signs of micro- and macroangiopathic
      haemolytic anaemia. The aim was to evaluate automated fragmented red cell (FRC)
      count compared to visual microscopy, and to assess FRCs in the presence of
      microcytosis and hypochromia using Sysmex automated counters. METHODS:
      Schistocytes were determined with visual microscopy after the observation of 1000
      erythrocytes, and the automated counting with Sysmex XE-5000. Indices of
      microcytosis (%MicroR) and hypochromia (%Hypo-He) were also analysed in the XE
      5000 analyser. RESULTS: Linear regression analysis showed a good correlation
      between automated and manual FRC% count (r = 0.824, P < 0.0001), but Bland
      Altman's plot revealed an overestimation of FRC of 0.82%. There is a global
      correlation between %MicroR and FRCs. In subgroup analysis of %MicroR (reference
      value: 0.3-3%, mild microcytosis: 3.1-7.2% and severe microcytosis: 7.3-56.7%),
      no correlations with automated %FRC were noticed (P > 0.05). Based on %Hypo-He
      subgroups (mild hypochromia: 1.2-5.2%, and severe hypochromia: 5.3-35.4%), a
      significant correlation of automated %FRC with mild hypochromia was found (r =
      0.621, P < 0.01). CONCLUSION: Despite the agreement between FRC count and the
      manual method, the overvaluation of FRC was high, leading to false-positive
      results. Microcytosis appeared to have no impact on FRC count, whereas mild
      hypochromia seemed to be related with FRC count. Particular attention is required
      to assess automated FRCs in samples with mild hypochromia.

PMID- 23134355
TI  - Compounding errors.

PMID- 23134356
TI  - Progression of RAS-mutant leukemia during RAF inhibitor treatment.
AB  - Vemurafenib, a selective RAF inhibitor, extends survival among patients with BRAF
      V600E-mutant melanoma. Vemurafenib inhibits ERK signaling in BRAF V600E-mutant
      cells but activates ERK signaling in BRAF wild-type cells. This paradoxical
      activation of ERK signaling is the mechanistic basis for the development of RAS
      mutant squamous-cell skin cancers in patients treated with RAF inhibitors. We
      report the accelerated growth of a previously unsuspected RAS-mutant leukemia in
      a patient with melanoma who was receiving vemurafenib. Exposure to vemurafenib
      induced hyperactivation of ERK signaling and proliferation of the leukemic cell
      population, an effect that was reversed on drug withdrawal.

PMID- 23134357
TI  - Regulating compounding pharmacies after NECC.

PMID- 23134358
TI  - The use of epidemiology in alcohol research.
AB  - AIMS: This paper presents examples to illustrate the utility and limitations in
      the use of epidemiology in alcohol research and discusses some promising new
      directions. METHODS: Review of literature, concentrating on epidemiological
      alcohol research with relevance to public health. FINDINGS AND CONCLUSION:
      Epidemiology offers tools for assessment of causes and effects of alcohol
      consumption as well as the effects of efforts to prevent alcohol consumption and
      its consequences. Epidemiological studies have made significant contributions to
      alcohol research with respect to public health and public policy. Fixed-effects
      modelling, difference-in-differences estimation and integrated qualitative and
      epidemiological methods are promising but underused methods in epidemiological
      studies. Many epidemiological studies have limited transferability of knowledge
      to other cultures and jurisdictions.

PMID- 23134359
TI  - The phosphoinositide 3-kinase pathway in chronic lymphocytic leukemia: evidence
      for phosphatase and tensin homolog deletion on chromosome 10 deregulation.

PMID- 23134360
TI  - Columnar-lined esophagus in Chinese patients with proximal gastric carcinomas.
AB  - OBJECTIVE: To investigate the clinicopathological features of columnar-lined
      esophagus (CLE) in Chinese patients. METHODS: Among 182 consecutive resections of
      proximal gastric cancer with residual esophageal tissue, 114 were eligible for
      the study. The maximal lengths of CLE and superficial esophageal glands (SEG) and
      the presence or absence of chronic inflammation (CI), lymphoid follicles (LF),
      Helicobacter pylori (H. pylori) infection, intestinal metaplasia (IM), pancreatic
      metaplasia (PM) and dysplasia were analyzed and compared with those in the
      adjacent proximal gastric mucosa. RESULTS: SEG were present in 110 cases with a
      mean length of 5.4 mm (range 1-16 mm, 90% equal to or under 10 mm and 10% between
      11-16 mm). These glands were associated with CI (95%), LF (85%), H. pylori
      infection (42%), IM (25%), PM (36%) and dysplasia (10%). CLE was found in 65% of
      the cases and was associated with SEG (mean length of 4.0 mm, range 1-13 mm, 97%
      within 10 mm and 3% between 11-13 mm). The frequencies of CI (97%), LF (86%), H.
      pylori infection (65%) and PM (46%) in CLE were similar to those in the proximal
      stomach (CI 90%, LF 54%, H. pylori infection 58%, PM 39%). In contrast, the
      frequencies of IM (37%) and dysplasia (15%) in CLE were significantly lower than
      those in the proximal stomach (66% and 31%, respectively; P < 0.01). CONCLUSIONS:
      CLE in Chinese patients was within 10 mm in length in 97% of cases, and with SEG
      and H. pylori infection-related changes similar to those in the proximal stomach.

PMID- 23134361
TI  - Systemic corticosteroids for community-acquired pneumonia: reasons for use and
      lack of benefit on outcome.
AB  - BACKGROUND AND OBJECTIVE: Although the benefits of systemic corticosteroids in
      community-acquired pneumonia (CAP) are not clear, their use is frequent in
      clinical practice. We described the frequency of this practice, patients'
      characteristics and its clinical impact. METHODS: We investigated all adult CAP
      patients visited between June 1997 and January 2008 (n = 3257). RESULTS: Two
      hundred and sixty patients received systemic corticosteroids (8%) with a mean
      daily dose of 45 (33) mg (median, 36 mg/day). Patients receiving corticosteroids
      were older (74 (13) vs 65 (19) years), had more comorbidities (respiratory, 59%
      vs 38%, cardiac, 29% vs 16%, etc.), higher Pneumonia Severity Index (Fine IV-V,
      76% vs 50%) and had received inhaled corticosteroids (36% vs 15%) and previous
      antibiotics (31% vs 23%) more frequently (P < 0.01, each). Significant predictors
      of corticosteroid administration were: chronic obstructive pulmonary disease
      (odds ratio (OR), 1.91), fever (OR, 0.59), expectoration (OR, 1.59), creatinine
      (+1 mg/dL, OR, 0.92), SaO(2) >= 92% (OR, 0.46), C-reactive protein (+5 mg/dL; OR,
      0.92) and cardiac failure (OR, 1.76). Mortality (6% vs 7%; P = 0.43) and time to
      clinical stability (4 (3-6) vs 5 (3-7) days; P = 0.11) did not differ between the
      two groups, while length of hospital stay was longer for the steroid group (9 (6
      14) vs 6 (3-9) days; P < 0.01). CONCLUSIONS: The main reasons for administering
      systemic steroids were the presence of chronic respiratory comorbidity or severe
      clinical presentation, but therapy did not influence mortality or clinical
      stability; by contrast, steroid administration was associated with prolonged
      length of stay. Nevertheless the steroid group did not show an increased
      mortality as it was expected according to the initial Pneumonia Severity Index
      score. Influence of steroids on outcomes of CAP need to be further investigated
      through randomized clinical trial.

PMID- 23134362
TI  - Characterization of therapeutic antibodies and related products.

PMID- 23134363
TI  - Autoantibodies and decreased expression of the transcription factor ELF-3
      together with increased chemokine pathways support an autoimmune phenotype and
      altered differentiation in lichen planus located in oral mucosa.
AB  - BACKGROUND: The pathogenesis of oral lichen planus (OLP), a chronic inflammatory
      disease, is not fully understood. It is known that OLP has autoimmune features,
      and it is suggested to be an autoimmune disease. ELF-3 is involved in
      differentiation of keratinocytes and deregulated in different tumours and
      inflammatory diseases. CXCR-3 and its ligands CXCL-10 and CXCL-11 are increased
      in autoimmune diseases and linked to Th-1 immune response. OBJECTIVES: To analyse
      and compare expression of ELF-3, CXCR-3, CXCL-10 and CXCL-11 in OLP lesions and
      controls in whole and microdissected epithelium. METHODS: Tissue biopsies from 20
      patients clinically and histologically diagnosed with OLP and 20 healthy controls
      were studied using whole tissues or microdissected epithelium. By the use of qRT
      PCR, mRNA levels of ELF-3, CXCR-3, CXCL-10 and CXCL-11 were studied. Western blot
      was used for analysis of ELF-3 protein expression. Sera from 19 OLP patients and
      20 controls were analysed with ELISA in search for autoantibodies. Results  The
      upregulation of CXCR-3, CXCL-10 and CXCL-11 found in OLP is similar to previous
      findings showing an autoimmune phenotype in lichen planus (LP) and lichen
      sclerosus. Decreased expression of the differentiation-related transcription
      factor ELF-3 was also seen in OLP lesions, and we further demonstrate presence of
      circulating autoantibodies against the ELF-3 protein in sera from 3 of 19 (16%)
      LP patients tested. CONCLUSIONS: On the basis of these findings, we confirm that
      OLP shows features of an autoimmune disease and suggest deregulated
      differentiation of keratinocytes to be one of the causes of the disease
      phenotype.

PMID- 23134364
TI  - Diastolic mitral regurgitation in 2:1 atrioventricular block: insight of the
      diastolic pressure.

PMID- 23134365
TI  - Insights into the low-temperature adaptation and nutritional flexibility of a
      soil-persistent Escherichia coli.
AB  - An understanding of the survival capacity of Escherichia coli in soil is critical
      for the evaluation of its role as a faecal indicator. Recent reports that E. coli
      can become long-term residents in maritime temperate soils have raised the
      question of how the organism survives and competes for niche space in the
      suboptimal soil environment. The ability of an environmental isolate to utilize
      380 substrates was assessed together with that of a reference laboratory strain
      (E. coli K12) at both 15 and 37  degrees C. At 15  degrees C, the environmental
      strain could utilize 161 substrates, with only 67 utilizable by the reference
      strain, while at 37  degrees C, 239 and 223 substrates could be utilized by each
      strain respectively. An investigation into the cold response of the strains
      revealed that E. coli K12 was found to reduce the expression of biosynthetic
      proteins at 15  degrees C, while the environmental isolate seemed to switch on
      proteins involved in stress response, suggesting low-temperature adaptation in
      the latter. Taken together, the results indicate that the environmentally
      persistent E. coli strain is well adapted to use a wide range of nutrient sources
      at 15  degrees C and to direct its protein expression to maintain a relatively
      fast growth rate at low temperature.

PMID- 23134366
TI  - Blame it on patriarchy: more sexist attitudes are associated with stronger
      consideration of cosmetic surgery for oneself and one's partner.
AB  - In the present work, we examined associations between oppressive, sexist beliefs
      and consideration of cosmetic surgery for oneself and also endorsement of
      cosmetic surgery for one's romantic partner. A total of 554 German-speaking
      volunteers from the community, mainly in Austria, completed measures of
      consideration of cosmetic surgery and three measures of sexist attitudes, while a
      subset of participants in romantic relationships completed a measure of
      endorsement of cosmetic surgery for their partners along with the measures of
      sexism. Preliminary analyses showed that women and single respondents were more
      likely to consider having cosmetic surgery than men and committed respondents,
      respectively. Further analyses showed that consideration of cosmetic surgery for
      oneself was significantly associated with sexist attitudes, particularly hostile
      attitudes to women. In addition, among participants in a relationship, sexist
      attitudes were associated with endorsement of cosmetic surgery for one's partner.
      These results indicate that attitudes to cosmetic surgery for oneself and one's
      partner are shaped by gender-ideological belief systems in patriarchal societies.
      Possible implications for understanding the motivations for having cosmetic
      surgery, among both single respondents and couples, are discussed. 

PMID- 23134367
TI  - Psychiatric disorder-related abnormal behavior and habenulointerpeduncular
      pathway defects in Wnt1-cre and Wnt1-GAL4 double transgenic mice.
AB  - The neural crest is a unique structure in vertebrates. Wnt1-cre and Wnt1-GAL4
      double transgenic (dTg) mice have been used in a variety of studies concerning
      neural crest cell lineages in which the Cre/loxP or GAL4/UAS system was applied.
      Here, we show psychiatric disorder-related behavioral abnormalities and
      histologic alterations in a neural crest-derived brain region in dTg mice. The
      dTg mice exhibited increased locomotor activity, decreased social interaction,
      and impaired short-term spatial memory and nesting behavior. The choline
      acetyltransferase- and vesicular glutamate transporter 2-immunoreactive
      habenulointerpeduncular fiber tracts that project from the medial habenular
      nucleus of the epithalamus to the interpeduncular nucleus of the midbrain
      tegmentum appeared irregular in the dTg mice. Both the medial habenula nucleus
      and the interpeduncular nucleus were confirmed to be derived from the neural
      crest. The findings of this study suggest that neural crest-derived cells have
      pathogenic roles in the development of psychiatric disorders and that the dTg
      mouse could be a useful animal model for studying the pathophysiology of mental
      illness such as autism and schizophrenia. Scientists that use the dTg mice as a
      cre-transgenic deleter line should be cautious in its possible toxicity,
      especially if behavioral analyses are to be performed.

PMID- 23134368
TI  - Acid-base property of N-methylimidazolium-based protic ionic liquids depending on
      anion.
AB  - Proton-donating and ionization properties of several protic ionic liquids (PILs)
      made from N-methylimidazole (Mim) and a series of acids (HA) have been assessed
      by means of potentiometric and calorimetric titrations. With regard to strong
      acids, bis(trifluoromethanesulfonyl) amide (Tf(2)NH) and trifluoromethanesulfonic
      acid (TfOH), it was elucidated that the two equimolar mixtures with Mim almost
      consist of ionic species, HMim(+) and A(-), and the proton transfer equilibrium
      corresponding to autoprotolysis in ordinary molecular liquids was established.
      The respective autoprotolysis constants were successfully evaluated, which
      indicate the proton-donating abilities of TfOH and Tf(2)NH in the respective PILs
      are similar. In the case of trifluoroacetic acid, the proton-donating ability of
      CF(3)COOH is much weaker than those of TfOH and Tf(2)NH, while ions are
      predominant species. On the other hand, with regard to formic acid and acetic
      acid, protons of these acids are suggested not to transfer to Mim sufficiently.
      From calorimetric titrations, about half of Mim is estimated to be proton
      attached at most in the CH(3)COOH-Mim equimolar mixture. In such a mixture,
      hydrogen-bonding adducts formation has been suggested. The autoprotolysis
      constants of the present PILs show a good linear correlation with dissociation
      constants of the constituent acids in an aqueous phase.

PMID- 23134370
TI  - Adjusting the stability of metal-organic frameworks under humid conditions by
      ligand functionalization.
AB  - The practical use of metal-organic frameworks (MOFs) in applications ranging from
      adsorption separations to controlled storage and release hinges on their
      stability in humid or aqueous environments. The sensitivity of certain MOFs under
      humid conditions is well-known, but systematic studies of water adsorption
      properties of MOFs are lacking. This information is critical for developing
      design criteria for directing future synthesis efforts. The goal of this work is
      to understand the influence of the extent of Zn-O bond shielding on the relative
      stabilities of MOFs belonging to same family of isostructural, noncatenated
      pillared MOFs [Zn(L)(DABCO)(0.5)], where L is the functionalized BDC (1,4
      benzenedicarboxylic acid) linker. The different extent of Zn-O bond shielding is
      provided by incorporating a broad range of functional groups on the BDC ligand.
      The resulting MOFs have varying surface areas, pore sizes, and pore volumes.
      Stability is assessed through water vapor adsorption isotherms combined with
      powder X-ray diffraction (PXRD) experiments and surface area analyses. Our study
      demonstrates that integration of polar functional groups (e.g., nitro, bromo,
      chloro, hydroxy, etc.) on the dicarboxylate linker renders these MOFs water
      unstable compared to the parent MOF as these polar functional groups have a
      negative shielding effect; i.e., they facilitate hydrolysis of the Zn-O bond. On
      the other hand, placing nonpolar groups (e.g., methyl) on the BDC ligand results
      in structurally robust MOFs because the Zn-O bond is effectively shielded from
      attack by water molecules. Therefore, the anthracene- and tetramethyl-BDC MOFs do
      not lose crystallinity or surface area after water exposure, in spite of the
      large amount of water adsorption due to capillary condensation at ~20% relative
      humidity (RH). This has been observed rarely in the MOF literature. The results
      of this work show that by ligand functionalization it is possible to adjust the
      water stability of a pillared MOF in both the positive and negative directions
      and, thus, provide an important step toward understanding the water adsorption
      behavior of MOFs.

PMID- 23134369
TI  - Integration of the metabolic/redox state, histone gene switching, DNA replication
      and S-phase progression by moonlighting metabolic enzymes.
AB  - The concept of one-protein-multiple-function, i.e. moonlighting proteins, is an
      ever-expanding paradigm. We obtained compelling evidence that an array of
      'cytoplasmic' metabolic enzymes can enter the nuclei to carry out moonlighting
      transcription functions; this phenomenon is conserved from Drosophila to humans.
      Of particular interest are the classical glycolytic enzymes GAPDH (glyceraldehyde
      3-phosphate dehydrogenase) and LDH (lactate dehydrogenase), which utilize NAD(H)
      as coenzymes and not only moonlight (in their nuclear forms) to regulate the
      transcription of S-phase-specific histone genes, but also act as metabolic/redox
      sensors that link histone gene switching to DNA replication and S-phase
      progression. 

PMID- 23134371
TI  - Compounds from the roots of Jasminum sambac.
AB  - Four new compounds (+)-jasminoids A, B, C, and D, together with seven known
      compounds, were isolated from the roots of Jasminum sambac. Their structures were
      identified using spectroscopic methods. This study provides a better
      understanding to the chemical composition of J. sambac roots that have been
      thought to be one ingredient of an ancient prescription 'Ma-Fei-San'.

PMID- 23134374
TI  - Differences in obsessive-compulsive symptoms and obsessive beliefs: a comparison
      between African Americans, Asian Americans, Latino Americans, and European
      Americans.
AB  - Clinical research has increasingly considered ethnic group differences in the
      expression of anxiety disorders, but to date few investigations have focused
      specifically on the symptoms of obsessive-compulsive disorder (OCD). We examined
      group differences in OC symptoms, related cognitions ("obsessive beliefs"), and
      their associations. The sample included European American (N = 1199), African
      American (N = 215), Asian American (N = 116), and Latino American (N = 72)
      participants. African American and Asian American participants reported more
      contamination-related OC symptoms than did European Americans. Asian Americans
      also reported elevated levels of obsessive beliefs. Moreover, group membership
      moderated the relationship between obsessive beliefs and certain dimensions of OC
      symptoms. These findings suggest group differences in the experience of OC
      symptoms and related cognitions, and that the cognitive-behavioral model of some
      OC symptoms could be refined and tailored for groups underrepresented in OCD
      research to date.

PMID- 23134375
TI  - Evaluation of cosmetic product exposures reported to the Milan Poison Control
      Centre, Italy from 2005 to 2010.
AB  - INTRODUCTION: To the average consumer, "cosmetics" are not considered to cause
      damage to human health under normal conditions of use. Thus, cosmetic "safety"
      does not require any particular attention to the possibility that cosmetics may
      result in a toxic exposure, especially for children. Poison Control Centres
      (PCCs) provide specialized and rapid information for consumers and health
      professionals to ensure management of events related to the exposures to
      different agents, including Cosmetics. Poison Control Centres also represent a
      unique source of information to investigate the frequency and type of exposures
      to cosmetic and the related risks. OBJECTIVE: An analysis of cases concerning
      human exposures to cosmetics collected from 2005 to 2010 by the PCC at the
      Ospedale Niguarda Ca' Granda (Milan, Italy) was performed. RESULTS: During this
      period, 11 322 human exposure cases related to cosmetics were collected
      accounting for 4.5% of the total human clinical cases. Almost, all the requests
      for assistance came from consumers (53%) and hospitals (40%). The most frequently
      reported site of exposure was the consumer's own residence (94%). The exposures
      mainly involved children younger than 4 years (77%). No difference in gender
      distribution was observed (female 49%, male 51%). Almost, all of the exposures
      were unintentional (94%). Intentional exposures, mainly related to suicide
      attempts and accounted for 6% of cases involving persons aged more than 12 years.
      Personal hygiene products (30%), perfumes and hair care products (excluding hair
      dyes) (both 13%) were the most frequently involved categories. Symptoms were
      present only in 26% of the exposures and were mostly gastrointestinal (46%). Most
      of the cases were managed at home (43%) whereas hospital intervention was
      required in 38%. CONCLUSION: Since the exposure frequency seems more likely to
      reflect product availability and accessibility to ingestors, our results call for
      closer attention to this type of hazard, especially for children younger than 4
      years of age.

PMID- 23134376
TI  - Chemical and bioactive quality traits during fruit ripening in eggplant (S.
      melongena L.) and allied species.
AB  - A chemical and bioactive quality evaluation of phytochemicals content of 10
      eggplant lines and three allied species (S. sodomaeum, S. aethiopicum and S.
      integrifolium) was performed. The eggplant lines were divided into the two
      subgroups of delphinidin-3-rutinoside (D3R) and nasunin (NAS) typologies, on the
      basis of the anthocyanin detected in their fruit skin. The allied species had
      higher glycoalkaloids content, lower soluble solids and PPO activity and absence
      of anthocyanins compared to the eggplant lines; S. sodomaeum stood out for high
      phenols content. Orthogonal contrast revealed a higher sugar content and low PPO
      activity in NAS- compared to D3R-typologies, whereas higher chlorogenic acid and
      anthocyanin contents were present in D3R-typologies. The main effect of the
      ripening was a decrease in phenols and in the PPO activity, not evidenced in S.
      sodomaeum, and an increase of glycoalkaloids in overripe fruits.  A good
      relationship was found between superoxide anion scavenging capacity and
      chlorogenic acid. This study highlighted the pattern of accumulation, also
      evidencing variations, of several phytochemicals during the eggplant fruit
      development and ripening.

PMID- 23134377
TI  - Testing theory in interprofessional education: social capital as a case study.
AB  - Theory is essential to understand our interprofessional educational (IPE)
      practice. As a discipline, IPE has moved from being widely atheoretical to having
      a plethora of theories imported from the psychosocial disciplines that have
      utility to understand, articulate and improve IPE practice and evaluation. This
      paper proposes that when taking this deductive approach to theoretical
      development in IPE, a greater focus must now be placed on the rigorous testing of
      these theories within the IPE context. It synthesizes two approaches to achieving
      this, using the social capital theory as a case study, and focuses on the first
      two stages of this synthesis: first, the identification of the concepts and
      propositions that make up a theory within the study context and second, the value
      based judgments made by the researcher and other stakeholders on the utility of
      these propositions. The interprofessional student group is chosen as a possible
      exemplar of a social network and theory-derived concepts and propositions are
      identified and classified within this context. With a focus on physical network
      characteristics, validation of these propositions with a sample of IPE
      educationalists is described. We present a range of propositions specifically
      related to the size and mix of IPE student groups, the frequency and level with
      which students participate in these as well as some of the existing evidence that
      have explored these propositions to date. Refined propositions and the way
      forward in the future application and empirical testing of social capital theory
      in IPE are presented.

PMID- 23134378
TI  - Physicians' perceptions of physician-nurse collaboration in Japan: effects of
      collaborative experience.
AB  - Studies of physician-nurse relationships have focused mainly on nurses'
      perceptions. Few studies have explored physicians' perceptions and related
      factors. This study had two aims: to describe physicians' perceptions of
      physician-nurse collaboration in Japan by focusing on attitudes toward
      collaboration and collaborative practice and to examine the effect of physicians'
      experiences related to collaboration on their perceptions of collaboration. A
      cross-sectional survey was conducted. Of the 520 physicians from four hospitals,
      248 completed the survey. The survey included the Jefferson Scale of attitudes
      toward physician-nurse collaboration, the collaborative practice scales, learning
      experiences related to collaboration with nurses and experiences of joint
      activities with nurses. Multiple regression analysis revealed that learning
      experiences in undergraduate and out-of-hospital education and experiences of
      joint committee work were significantly associated with higher collaborative
      practice scores. Although participants' attitude scores had a strong association
      with practice scores, there were no variables significantly associated with the
      attitude score. This study supported the importance of education in undergraduate
      courses and suggested that it should be ongoing after qualification. Joint
      activities other than daily practice, such as continuous quality improvement,
      might also be effective. Factors that improve physicians' attitudes toward
      collaboration should be further explored.

PMID- 23134379
TI  - Expression of autophagy-related markers beclin-1, light chain 3A, light chain 3B
      and p62 according to the molecular subtype of breast cancer.
AB  - AIMS: To investigate the relationship between the expression of autophagy-related
      proteins, including beclin-1, light chain (LC) 3A, LC3B, and p62, and prognosis
      in invasive breast cancer. METHODS AND RESULTS: We constructed tissue microarrays
      from the breast cancer cells of 489 patients, and classified molecular subtypes
      using surrogate immunohistochemical stains. The tumoral expression levels of LC3A
      and LC3B were highest in triple-negative breast cancer (TNBC) (P < 0.001),
      whereas these types of tumour had the lowest expression levels of these markers
      in the stroma (P = 0.005 and P < 0.001, respectively). Cytoplasmic beclin-1
      expression was highest in TNBC, but nuclear expression was lowest (P < 0.001).
      p62 cytoplasmic and nuclear expression were highest in HER2-type tumours (P =
      0.001 and P < 0.001, respectively). Tumoral LC3A and LC3B expression were
      associated with high histological grade (P < 0.001, and P < 0.028, respectively),
      but nuclear p62 expression was associated with lower histological grade (P =
      0.004). CONCLUSIONS: Autophagy-related markers are differentially expressed
      according to the molecular subtype of breast cancer. In particular, expression of
      LC3A, LC3B and beclin-1 was highest in TNBC tumour cells, whereas that of LC3A
      and LC3B in the tumour stroma was lowest in TNBC.

PMID- 23134380
TI  - "If I had only known"--on choice and uncertainty in the ICU.
AB  - After receiving a ventricular assist device, a patient experiences months of
      advances and setbacks in the ICU. She's one of a new subcategory of ICU patients:
      the chronically critically ill. Their stories reveal shortcomings of common
      perspectives on medical decision making.

PMID- 23134381
TI  - Statin use and reduced cancer-related mortality.
AB  - BACKGROUND: A reduction in the availability of cholesterol may limit the cellular
      proliferation required for cancer growth and metastasis. We tested the hypothesis
      that statin use begun before a cancer diagnosis is associated with reduced cancer
      related mortality. METHODS: We assessed mortality among patients from the entire
      Danish population who had received a diagnosis of cancer between 1995 and 2007,
      with follow-up until December 31, 2009. Among patients 40 years of age or older,
      18,721 had used statins regularly before the cancer diagnosis and 277,204 had
      never used statins. RESULTS: Multivariable-adjusted hazard ratios for statin
      users, as compared with patients who had never used statins, were 0.85 (95%
      confidence interval [CI], 0.83 to 0.87) for death from any cause and 0.85 (95%
      CI, 0.82 to 0.87) for death from cancer. Adjusted hazard ratios for death from
      any cause according to the defined daily statin dose (the assumed average
      maintenance dose per day) were 0.82 (95% CI, 0.81 to 0.85) for a dose of 0.01 to
      0.75 defined daily dose per day, 0.87 (95% CI, 0.83 to 0.89) for 0.76 to 1.50
      defined daily dose per day, and 0.87 (95% CI, 0.81 to 0.91) for higher than 1.50
      defined daily dose per day; the corresponding hazard ratios for death from cancer
      were 0.83 (95% CI, 0.81 to 0.86), 0.87 (95% CI, 0.83 to 0.91), and 0.87 (95% CI,
      0.81 to 0.92). The reduced cancer-related mortality among statin users as
      compared with those who had never used statins was observed for each of 13 cancer
      types. CONCLUSIONS: Statin use in patients with cancer is associated with reduced
      cancer-related mortality. This suggests a need for trials of statins in patients
      with cancer.

PMID- 23134382
TI  - Reduced mortality with hospital pay for performance in England.
AB  - BACKGROUND: Pay-for-performance programs are being adopted internationally
      despite little evidence that they improve patient outcomes. In 2008, a program
      called Advancing Quality, based on the Hospital Quality Incentive Demonstration
      in the United States, was introduced in all National Health Service (NHS)
      hospitals in the northwest region of England (population, 6.8 million). METHODS:
      We analyzed 30-day in-hospital mortality among 134,435 patients admitted for
      pneumonia, heart failure, or acute myocardial infarction to 24 hospitals covered
      by the pay-for-performance program. We used difference-in-differences regression
      analysis to compare mortality 18 months before and 18 months after the
      introduction of the program with mortality in two comparators: 722,139 patients
      admitted for the same three conditions to the 132 other hospitals in England and
      241,009 patients admitted for six other conditions to both groups of hospitals.
      RESULTS: Risk-adjusted, absolute mortality for the conditions included in the pay
      for-performance program decreased significantly, with an absolute reduction of
      1.3 percentage points (95% confidence interval [CI], 0.4 to 2.1; P=0.006) and a
      relative reduction of 6%, equivalent to 890 fewer deaths (95% CI, 260 to 1500)
      during the 18-month period. The largest reduction, for pneumonia, was significant
      (1.9 percentage points; 95% CI, 0.9 to 3.0; P<0.001), with nonsignificant
      reductions for acute myocardial infarction (0.6 percentage points; 95% CI, -0.4
      to 1.7; P=0.23) and heart failure (0.6 percentage points; 95% CI, -0.6 to 1.8;
      P=0.30). CONCLUSIONS: The introduction of pay for performance in all NHS
      hospitals in one region of England was associated with a clinically significant
      reduction in mortality. As compared with a similar U.S. program, the U.K. program
      had larger bonuses and a greater investment by hospitals in quality-improvement
      activities. Further research is needed on how implementation of pay-for
      performance programs influences their effects. (Funded by the NHS National
      Institute for Health Research.).

PMID- 23134383
TI  - Hand eczema.
AB  - Hand eczema is an inflammation of the skin; the cause is often multifactorial.
      Initial management includes avoiding causative irritants or allergens (e.g., by
      wearing impermeable gloves) and applying emollients and potent topical
      glucocorticoids.

PMID- 23134384
TI  - Images in clinical medicine: Rhinophyma.
AB  - A 42-year-old man presented with impaired nasal breathing and a slowly growing
      mass on the tip of the nose. Examination revealed a multilobulated sebaceous
      nodule protruding from the nasal tip.

PMID- 23134385
TI  - Case records of the Massachusetts General Hospital: Case 34-2012: a 27-year-old
      woman in Ethiopia with severe pain, bleeding, and shock during labor.
AB  - A 27-year-old woman was admitted to a hospital in Ethiopia because of severe
      abdominal pain during labor, with cessation of contractions. She had been in
      labor at home, pushing for 24 hours. On arrival at the hospital 3 hours later,
      she was in shock. A procedure was performed.

PMID- 23134386
TI  - The promise of antibody-drug conjugates.

PMID- 23134387
TI  - Statins and cancer-related mortality--let's work together.

PMID- 23134388
TI  - Will pay for performance improve quality of care? The answer is in the details.

PMID- 23134389
TI  - Electronic health records and national patient-safety goals.
AB  - Hospitals and clinics are adapting to new technologies and implementing
      electronic health records, but the efforts need to be aligned explicitly with
      goals for patient safety. EHRs bring the risks of both technical failures and
      inappropriate use, but they can also help to monitor and improve patient safety.

PMID- 23134391
TI  - Quality-of-life effects of prostate-specific antigen screening.

PMID- 23134392
TI  - Quality-of-life effects of prostate-specific antigen screening.

PMID- 23134394
TI  - Bariatric surgery and prevention of type 2 diabetes.

PMID- 23134395
TI  - Bariatric surgery and prevention of type 2 diabetes.

PMID- 23134397
TI  - Antibiotic prevention of acute exacerbations of COPD.

PMID- 23134398
TI  - Antibiotic prevention of acute exacerbations of COPD.

PMID- 23134399
TI  - Antibiotic prevention of acute exacerbations of COPD.

PMID- 23134400
TI  - Antibiotic prevention of acute exacerbations of COPD.

PMID- 23134401
TI  - Antibiotic prevention of acute exacerbations of COPD.

PMID- 23134402
TI  - A sea-urchin spine chilling remedy.

PMID- 23134404
TI  - Monitoring ventilation with capnography.
AB  - Capnography, the graphic display of the exhaled and inhaled carbon dioxide
      concentration plotted against time, is used to monitor ventilation. This video
      reviews the principles of capnography and explains how to interpret the
      information it provides.

PMID- 23134405
TI  - Images in clinical medicine: Giant basilar-artery aneurysm.

PMID- 23134406
TI  - Synthesis of tetrasubstituted cyclopentadienes via palladium-catalyzed reaction
      of (Z)-2-en-4-yn acetates and N-methyl indoles.
AB  - An efficient approach for the synthesis of tetrasubstituted cyclopentadienes
      through Pd-catalyzed reactions of (Z)-2-en-4-yn acetates with substituted indoles
      was developed. This methodology has the advantages of broad scope, simple
      conditions and easily accessible starting materials.

PMID- 23134407
TI  - Modified technique for spermatogonial stem cell transplantation into the
      seminiferous tubules in mouse model.
AB  - This study aimed to develop a modified technique for spermatogonial stem cell
      (SSC) transplantation with the aid of an operating microscope in an infertile
      mouse model. Male neonatal C57BL/6 (B6) mice served as SSC donors. SSCs labeled
      with the PKH26-GL marker were detected by flow cytometry to verify purity. Adult
      B6 males were rendered infertile by busulfan treatment as the recipient. One
      month later the SSC suspension was delivered into recipient seminiferous tubules
      by manual microinjection under microscope with 100x magnification. This was
      compared to the conventional mechanical micromanipulator method via efferent
      ducts, rete testis, and seminiferous tubules, respectively. The volume injected
      and time required in the different procedures were compared. The recipient
      accepted manual microinjection via seminiferous tubules was subjected to
      histology, confocal laser scanning microscopy, and real-time fluorescent PCR at
      different checkpoints after transplantation. Positive controls received neither
      busulfan treatment nor transplantation. Negative controls were injected with an
      equal amount of transplant medium. The results showed that manual microinjection
      took 10 minutes per testis for the complete delivery of 50 ul of the SSC
      suspension, which was significantly less time-consuming and delivered a larger
      volume of SSC suspension than other methods. Transplanted SSCs demonstrated the
      earliest transference and colonization in recipient testes 7 days after
      transplantation. The newly generated germ cell layers appeared to be intact
      during spermatogenesis 90-days post-transplantation. This manual injection
      technique under microscope provides an alternative method to deliver the SSCs
      into the recipient seminiferous tubules.

PMID- 23134408
TI  - Safety and efficacy of four steroid-minimization protocols in liver transplant
      recipients: 3-year follow-up in a single center.
AB  - OBJECTIVE: To evaluate the safety and efficacy of steroid-minimization therapy in
      liver transplantation (LT) recipients with hepatitis B virus-related diseases in
      China. METHODS: From March 2000 to June 2007, 502 adult LT recipients, mostly
      with hepatitis B (HBV)-related diseases, were enrolled in our study. Four study
      groups were setup according to the steroid-minimization protocols: tacrolimus
      (TAC) with 6 months steroids withdrawal (6M SW), TAC with 3 months SW (3M SW),
      TAC with 14 days SW (14d SW), and TAC with basiliximab induction and steroids
      avoidance (Bas SA). All patients were followed up for at least 36 months after
      LT. RESULTS: There were no significant differences in the overall 3-year survival
      rates of the patients and graft, and chronic rejection among the four groups (P =
      0.092, P = 0.113 and P = 0.684, respectively). There was also no difference in
      acute rejection within 12 months after LT (P = 0.514). The 3-year recurrence
      rates of HBV infection and hepatocellular carcinoma (HCC) after LT were
      significantly different among all the groups (lowest in TAC/Bas SA group; P =
      0.037 and P = 0.029, respectively). The overall incidence of infection was
      significantly higher in the 6M SW group (62.2% vs 56.1% in 3M SW, 30.5% in 14d
      SW, 20.5% in Bas SA; P < 0.01). By the end of the 3-year follow-up, more than 90%
      of the surviving patients could safely receive TAC monotherapy. CONCLUSION: Bas
      SA immunosuppressive protocol can be achieved safely in LT and reduce HBV
      infection and HCC recurrence and side effects of steroids after LT.

PMID- 23134409
TI  - Mesityltellurenyl cations stabilized by triphenylpnictogens [MesTe(EPh(3))](+) (E
      = P, As, Sb).
AB  - The homoleptic 1:1 Lewis pair (LP) complex [MesTe(TeMes2)]O3SCF3 (1) featuring
      the cation [MesTe(TeMes2)](+) (1a) was obtained by the reaction of Mes2Te with
      HO3SCF3. The reaction of 1 with Ph3E (E = P, As, Sb, Bi) proceeded with
      substitution of Mes2Te and provided the heteroleptic 1:1 LP complexes
      [MesTe(EPh3)]O3SCF3 (2, E = P; 3, E = As) and [MesTe(SbPh3)][Ph2Sb(O3SCF3)2] (4)
      featuring the cations [MesTe(EPh3)](+) (2a, E = P; 3a, E = As; 4a, E = Sb) and
      the anion [Ph2Sb(O3SCF3)2](-) (4b). In the reaction with Ph3Bi, the crude product
      contained the cation [MesTe(BiPh3)](+) (5a) and the anion [Ph2Bi(O3SCF3)2](-)
      (5b); however, the heteroleptic 1:1 LP complex [MesTe(BiPh3)][Ph2Bi(O3SCF3)2] (5)
      could not be isolated because of its limited stability. Instead, fractional
      crystallization furnished a large amount of Ph2BiO3SCF3 (6), which was also
      obtained by the reaction of Ph3Bi with HO3SCF3. The formation of the anions 4b
      and 5b involves a phenyl group migration from Ph3E (E = Sb, Bi) to the MesTe(+)
      cation and afforded MesTePh as the byproduct, which was identified in the mother
      liquor. The heteroleptic 1:1 LP complexes 2-4 were also obtained by the one-pot
      reaction of Mes2Te, Ph3E (E = P, As, Sb) and HO3SCF3. Compounds 1-4 and 6 were
      investigated by single-crystal X-ray diffraction. The molecular structures of 1a
      4a were used for density functional theory calculations at the B3PW91/TZ level of
      theory and studied using natural bond order (NBO) analyses as well as real-space
      bonding descriptors derived from an atoms-in-molecules (AIM) analysis of the
      theoretically obtained electron density. Additionally, the electron
      localizability indicator (ELI-D) and the delocalization index are derived from
      the corresponding pair density. 

PMID- 23134410
TI  - Assessment of the platelet parameters and serum butyrylcholinesterase activity in
      type 1 diabetes patients with ketoacidosis.
AB  - The potential roles of serum butyrylcholinesterase (BChE) activity and platelet
      indices in type 1 diabetes (T1D) remain uncertain. We aimed to investigate the
      correlation among the platelet indices, serum BChE activity, and diabetic
      ketoacidosis (DKA). Sixty-one T1D patients, 29 patients with DKA, and 30 age- and
      sex-matched controls were enrolled. Mean platelet volume (MPV), platelet
      distribution width (PDW), and serum BChE activity were measured and evaluated at
      admission and after the treatment. The serum BChE activity was significantly
      lower in patients with DKA at admission to the hospital compared with non-DKA and
      control subjects; however, plasma glucose level, HbA1c level, MPV and PDW were
      significantly higher. Serum BChE activity, variables related to glycemic control,
      and platelet parameters were higher in non-DKA patients than in controls. Serum
      BChE activity was correlated with the serum HCO3 level (r = 0.375, p < 0.05) and
      plasma glucose level (r = -0.387, p < 0.05). Receiver operating characteristic
      curve analyses showed no difference between serum BChE activity and the platelet
      parameters with respect to the ability to reflect DKA. Logistic regression showed
      that increased PDW can act as a risk marker for the presence of DKA. Serum BChE
      activity and the platelet parameters returned to normal along with the plasma
      glucose levels when metabolic acidosis was well controlled. Serum BChE activity
      and the platelet parameters were significantly correlated with DKA. Measurement
      of PDW can provide complementary information and a risk biomarker reflecting the
      presence of DKA.

PMID- 23134411
TI  - Bovine spongiform encephalopathy (BSE)-associated polymorphisms of the prion
      protein (PRNP) gene in Korean native cattle.

PMID- 23134412
TI  - Nanoparticle growth analysis by molecular dynamics: cubic seed.
AB  - Growth of a cubic nanoparticle was studied by classical molecular dynamics
      simulation for three seed sizes in nine different supersaturation ratios. Similar
      to the spherical seed in our previous study, for high supersaturation ratios, a
      two-stage phenomenon that consists of an initial heterogeneous growth around the
      seed and homogeneous nucleation at various sites within the system was observed.
      A decomposition of the distinct phenomenon was carried out and the results were
      compared to that from the spherical seed. The homogeneous nucleation
      characteristics for high supersaturation ratios show no significant difference,
      but as the supersaturation ratio decreases, the ratio of the nucleation rate for
      the systems with different seed shapes shows a deviation from unity. Other
      tendencies are nearly identical to that seen from the spherical seed study and
      the physical rationales are alike. The heterogeneous growth rate was greater by a
      factor of 3 to 10, even though the number of molecules in each seed class was
      nearly identical, which is evidence of a shape effect. Furthermore, cluster
      formation free energy analysis was conducted and the results were compared with
      the classical nucleation theory and condensation theory. The disk-shape
      modification of the classical nucleation theory was used for growth on the cubic
      seed and produced a similar deviation to that of the spherical seed, which used a
      cap-shape modification. Additionally, the condensation theory showed a better
      agreement compared with the sphere. Finally, the nanoparticle growth mechanism on
      the seeds along with the packing and surface diffusion characteristics was
      analyzed and showed why and how the nanoparticle grows.

PMID- 23134413
TI  - An interview with the author of this issue's Editorial.

PMID- 23134414
TI  - Chlamydial biology and its associated virulence blockers.
AB  - Chlamydiales are obligate intracellular parasites of eukaryotic cells. They can
      be distinguished from other Gram-negative bacteria through their characteristic
      developmental cycle, in addition to special biochemical and physical adaptations
      to subvert the eukaryotic host cell. The host spectrum includes humans and other
      mammals, fish, birds, reptiles, insects and even amoeba, causing a plethora of
      diseases. The first part of this review focuses on the specific chlamydial
      infection biology and metabolism. As resistance to classical antibiotics is
      emerging among Chlamydiae as well, the second part elaborates on specific
      compounds and tools to block chlamydial virulence traits, such as adhesion and
      internalization, Type III secretion and modulation of gene expression.

PMID- 23134415
TI  - Advances in fluorescence and bioluminescence imaging.

PMID- 23134416
TI  - Antioxidant and DNA-protective activities of chlorogenic acid isomers.
AB  - Chlorogenic acid is a well-known antioxidant and has more isomers according to
      the difference in binding location and number of caffeic on quinic acid. In this
      study, we investigated and compared the profiles of antioxidant and DNA
      protective activities of chlorogenic acid isomers including three caffeoylquinic
      acid isomers (3-O-caffeoylquinic acid, 3-CQA; 4-O-caffeoylquinic acid, 4-CQA; and
      5-O- caffeoylquinic acid, 5-CQA) and three dicaffeoylquinic acid isomers (3,5
      dicaffeoyl-quinic acid, ICAA; 3,4-dicaffeoylquinic acid, ICAB; and 4,5-dicaffeoyl
      quinic acid, ICAC). The results showed that each of chlorogenic acid isomers
      studied exhibited antioxidant activities and DNA damage protective effects to
      various extents. On the whole, dicaffeoylquinic acids possessed better
      antioxidant activities, mostly because they have more hydroxyl groups than
      caffeoylquinic acids. Three caffeoylquinic acid isomers showed quite similar
      antioxidant activities, indicating that the position of esterification on the
      quinic moiety of caffeoylquinic acid had no effect on its antioxidant activities.
      Quite the contrary, a difference among dicaffeoylquinic acid isomers was
      observed, namely, ICAA and ICAB exhibited the same antioxidant activities,
      whereas ICAC had higher antioxidant activities than ICAA and ICAB in some assays,
      which implied that their antioxidant activities were probably influenced by the
      position of esterification on the quinic moiety. We speculated that this
      difference might be due to the fact that there may exist a steric hindrance
      effect in the ICAC. However, this assumption needs to be further confirmed.

PMID- 23134417
TI  - Two new diterpenes, neocaesalpin MR and minaxin C, from Caesalpinia minax.
AB  - Two new cassane-type diterpenes, neocaesalpin MR and minaxin C, were isolated
      from Caesalpinia minax HANCE. The structures of these compounds were elucidated
      by means of spectroscopic analysis. Among these isolated compounds, neocaesalpin
      MR showed mild activities toward HeLa and colon cancer (HCT-8) human cancer cell
      lines.

PMID- 23134418
TI  - Co-morbidities in psoriasis: a hospital-based case-control study.
AB  - BACKGROUND: Recent researches show that psoriasis is frequently associated with
      systemic co-morbidities. OBJECTIVES: This study aimed to identify possible
      associated co-morbidities in psoriatic patients stratified by age and sex.
      METHODS: In this retrospective hospital-based case-control study, patients
      diagnosed as psoriasis at the Kaohsiung Veterans General Hospital in Taiwan
      between January 2008 and December 2009 were enrolled as cases and classified into
      severe and mild based on their use of systemic therapy. The controls were the
      patients without psoriasis matched the cases in 1 : 1 ratio with same birth year,
      sex and calendar date. Odds ratios (ORs) and 95% confidence intervals (CIs) from
      the conditional logistic regression method were used to assess the risk of co
      morbidities between psoriatic and non-psoriatic patients. RESULTS: A total of 447
      cases and 447 matched controls, with mean age of 51.3 +/- 18.3 years and male-to
      female ratio of 2.17 : 1 were enrolled. The ratio of mild-to-severe was 3.5 : 1.
      Compared with non-psoriatic patients, psoriatic patients had significantly higher
      OR of hypertension (1.85), diabetes mellitus (2.88) and obesity (1.66). Among
      those aged >=51 years old, there was significant risk in male psoriatic patients
      with ischaemic and hypertensive heart disease (IHHD) (OR = 2.167) after
      eliminating female IHHD psoriatic patients (OR = 0.125). Psoriasis was
      significantly negatively associated with cancers (OR = 0.267). Psoriasis patients
      often had the usual drinking habit (OR = 2.23) and seldom had an occasional
      drinking habit (OR = 0.25). CONCLUSIONS: Psoriasis is strongly associated with
      hypertension, diabetes mellitus and obesity. The association between psoriasis
      and IHHD, stroke, cancers, smoking and alcohol habits warrant more investigation.

PMID- 23134419
TI  - Sample size requirement for digital image analysis of collagen proportionate area
      in cirrhotic livers.
AB  - AIMS:    The requirements for adequate cirrhotic liver biopsy size have not been
      established for quantitative fibrosis measurements (collagen proportionate area:
      CPA). We evaluated the CPA of virtual biopsies in cirrhosis to elucidate (i) the
      amount of tissue required to achieve reliable CPA measurements and (ii) the
      effect of aetiology on sample size requirements. METHOD AND RESULTS:    A total
      of 120 cirrhotic tissue blocks (six aetiologies) were studied. A representative
      100 mm(2) region was selected from each block and a reference CPA measured. Each
      image (n = 120) was divided into 100 * 1 mm(2) images; CPA was measured for each
      1 mm(2) and virtual biopsies of different sizes were created from the 1 mm(2)
      components. For each virtual biopsy size the probability that the virtual biopsy
      CPA would be within 5% of the reference CPA was calculated. There were 441 000
      virtual biopsies. Biopsy size versus probability plots indicated that, for 90%
      probability that the virtual biopsy CPA can be expected to be within 5% of the
      reference CPA, 22-28 mm(2) of analysable tissue is required depending on liver
      disease aetiology; and that a 75% probability level requires a biopsy with 12-15
      mm(2) of analysable tissue. CONCLUSION:    The sample size required for a given
      probability level depends on the aetiology of cirrhosis, and this should be taken
      into account when judging the reliability of cirrhotic liver biopsy CPA.

PMID- 23134420
TI  - RCAN1 regulates vesicle recycling and quantal release kinetics via effects on
      calcineurin activity.
AB  - We have previously shown that Regulator of Calcineurin 1 (RCAN1) regulates
      multiple stages of vesicle exocytosis. However, the mechanisms by which RCAN1
      affects secretory vesicle exocytosis and quantal release kinetics remain unknown.
      Here, we use carbon fibre amperometry to detect exocytosis from chromaffin cells
      and identify these underlying mechanisms. We observe reduced exocytosis with
      repeated stimulations in chromaffin cells over-expressing RCAN1 (RCAN1(ox)), but
      not in wild-type (WT) cells, indicating a negative effect of RCAN1 on vesicle
      recycling and endocytosis. Acute exposure to calcineurin inhibitors, cyclosporine
      A and FK-506, replicates this effect in WT cells but has no additional effect in
      RCAN1(ox) cells. When we chronically expose WT cells to cyclosporine A and FK-506
      we find that catecholamine release per vesicle and pre-spike foot (PSF) signal
      parameters are decreased, similar to that in RCAN1(ox) cells. Inhibiting
      calcineurin activity in RCAN1(ox) cells has no additional effect on the amount of
      catecholamine release per vesicle but further reduces PSF signal parameters.
      Although electron microscopy studies indicate these changes are not because of
      altered vesicle number or distribution in RCAN1(ox) cells, the smaller vesicle
      and dense core size we observe in RCAN1(ox) cells may underlie the reduced
      quantal release in these cells. Thus, our results indicate that RCAN1 most likely
      affects vesicle recycling and quantal release kinetics via the inhibition of
      calcineurin activity.

PMID- 23134421
TI  - Tuning the reactivity of TEMPO by coordination to a Lewis acid: isolation and
      reactivity of MCl3(eta1-TEMPO) (M = Fe, Al).
AB  - Addition of 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) to MCl(3) (M = Fe, Al)
      results in the formation of MCl(3)(eta(1)-TEMPO) [M = Fe (1), Al (2)]. Both 1 and
      2 oxidize alcohols to generate ketones or aldehydes along with the reduced
      complexes MCl(3)(eta(1)-TEMPOH) [M = Fe (3), Al (4)]. Complexes 1-4 were fully
      characterized, including analysis by X-ray crystallography. Additionally, control
      experiments indicated that neither MCl(3) (M = Al, Fe) nor TEMPO are capable of
      effecting the oxidation of alcohols independently.

PMID- 23134422
TI  - Disorders of consciousness.

PMID- 23134423
TI  - Perceived game realism: a test of three alternative models.
AB  - Perceived realism is considered a key concept in explaining the mental processing
      of media messages and the societal impact of media. Despite its importance,
      little is known about its conceptualization and dimensional structure, especially
      with regard to digital games. The aim of this study was to test a six-factor
      model of perceived game realism comprised of simulational realism, freedom of
      choice, perceptual pervasiveness, social realism, authenticity, and character
      involvement and to assess it against an alternative single- and five-factor
      model. Data were collected from 380 male digital game users who judged the
      realism of the first-person shooter Half-Life 2 based upon their previous
      experience with the game. Confirmatory factor analysis was applied to investigate
      which model fits the data best. The results support the six-factor model over the
      single- and five-factor solutions. The study contributes to our knowledge of
      perceived game realism by further developing its conceptualization and
      measurement.

PMID- 23134424
TI  - Independent pathway formation of guest-host in host ternary complexes made of
      ammonium salt, calixarene, and cyclodextrin.
AB  - The interaction between gamma-cyclodextrin and amphiphilic p
      sulfonatocalix[4]arenes was studied using NMR and isothermal titration
      calorimetry techniques. The results indicate that these calixarenes are able to
      form 1:1, 1:2, and 2:1 host-guest complexes with the cyclodextrin. The ROESY
      spectra suggest that the cyclodextrin binds the calixarenes through the
      hydrophobic alkyl chains. p-Sulfonatocalix[4]arenes, which are traditionally used
      as host molecules, act as guests in the presence of gamma-cyclodextrin. However,
      their recognition site remains active upon complexation with the cyclodextrin,
      and ternary complexes can be devised. Here, we also demonstrate the formation of
      such complexes using tetramethylammonium chloride as a model guest. Moreover, it
      is also demonstrated that the recognition properties of the calixarene are
      unaffected upon complexation with the cyclodextrin.

PMID- 23134425
TI  - Signaling pathways involved in endoplasmic reticulum stress-induced neuronal
      apoptosis.
AB  - In eukaryotic cells, the endoplasmic reticulum (ER) is a very critical site for
      synthesis, folding, modification of protein, and calcium homeostasis. The ER
      responds to factors that perturb ER function such as the accumulation of unfolded
      proteins (ER stress) by activating unfolded protein response to relieve the
      stress. However, chronic or unresolved ER stress can induce neuronal apoptosis by
      activating c-Jun N-terminal kinase (JNK), glycogen synthase kinase 3/3beta
      (GSK3/3beta), CAAT/enhancer binding protein homologous protein (CHOP), and
      caspase-12 pathway. Research related to ER stress will provide therapeutic
      implications in neurological diseases.

PMID- 23134426
TI  - Successful treatment with thalidomide for a patient with recurrent
      gastrointestinal bleeding due to angiodysplasia diagnosed by capsule endoscopy.

PMID- 23134427
TI  - Avastin in glaucoma surgery...

PMID- 23134428
TI  - My friend deep anterior lamellar keratoplasty.

PMID- 23134429
TI  - Wheel-shaped icosanuclear homo- and heterometallic complexes of Ni(II), Co(II),
      and Cu(II) ions supported by unsymmetrical aminoalcohol ligands.
AB  - Reactions of M(OAc)2.4H2O (M = Ni, Co) with 3-[benzyl(2-hydroxyethyl)amino]-1
      propanol (H2L) in the presence of pyridine or triethylamine afforded novel
      homometallic icosanuclear wheel-shaped complexes [M20L4(HL)4(OAc)28] (M = Ni (1),
      Co (2)), which consist of a central M(II)12 single-stranded, nearly planar loop
      with four peripheral [M2(HL)(OAc)2] fragments attached in an S4 symmetrical
      fashion. The complexes can alternatively be recognized as saddle-shaped wheel
      structures, in which four tetranuclear units of [M4L(HL)(OAc)7](2-) are connected
      by four M(2+) ions (M5). The tetranuclear unit itself can be derived from an
      ideal C2 symmetrical [M4(HL)2(MU-eta(2)-OAc)4(MU-eta(1),eta(1)
      OAc)2(eta(1),eta(1)-OAc)](-) structure through deprotonation of the HL(-) ligand,
      and is composed of two plane-shared M3O4 incomplete cubanes in which the M2 and
      M3 atoms are involved in the central fused plane and the M1 and M4 atoms are
      disposed at the apex sites. Mixed-metal icosanuclear complexes [NixM20
      xL4(HL)4(OAc)28] (3, M = Co, x = 9.5) and [Ni12M8L4(HL)4(OAc)28] (4, M = Cu) were
      also synthesized by using equimolar amounts of Ni(II) and M(II) ions, and were
      shown to have similar structures to 1 and 2. X-ray crystallographic and
      fluorescent analyses revealed that complex 3 contains nonstoichiometric amounts
      of Ni(2+) and Co(2+) ions in the ratio of 9.5:10.5 and that these are disordered
      at every metal site. In striking contrast, complex 4 has a stoichiometric formula
      of Ni12Cu8, which was confirmed by the Jahn-Teller elongation of Cu(2+) ions, and
      consequently, the M2 and M5 positions are occupied exclusively by the Cu(2+)
      ions. The temperature-dependent direct current (dc) magnetic susceptibility data
      showed the presence of ferromagnetic exchange interactions in the Ni homometallic
      (1) and NiCu bimetallic (4) complexes, while the Co homometallic (2) and NiCo
      bimetallic (3) complexes exhibited antiferromagnetic interactions due to spin
      orbit coupling effects of the octahedral Co(II) ions. The present results
      demonstrate that the unsymmetrical aminoalcohol ligand H2L is quite effective in
      organizing the homo- and heterometallic icosanuclear wheel-shaped metal
      arrangements. 

PMID- 23134430
TI  - Identification of a novel HLA-A allele A*33:61 in a Chinese individual.
AB  - HLA-A*33:61 has two nucleotides change from A*33:03:01 at positions 559 and 560
      in exon 3 where A->C and C->G (codon 163 ACG->CGG).

PMID- 23134431
TI  - Alcohol intoxication in the context of major public holidays, sporting and social
      events: a time-series analysis in Melbourne, Australia, 2000-2009.
AB  - AIMS: To assess the relationship between ambulance attendances, emergency
      department (ED) presentations and hospital admissions for acute alcohol
      intoxication and the timing of public holidays, sporting and social events.
      DESIGN: Time-series analysis was used to explore trends in intoxication in the
      context of major events. SETTING: Population of Melbourne, Victoria, Australia
      between 2000 and 2009. PARTICIPANTS: All patients attended by ambulance,
      presenting to hospital EDs, or admitted to hospital who were classified as
      acutely alcohol intoxicated. MEASUREMENT: Analysis of daily numbers of
      presentations for acute alcohol intoxication associated with major events were
      undertaken, including lead and lag effects. Analyses controlled for day of week
      and month of year to address temporal and seasonal variations. FINDINGS: Alcohol
      intoxication presentations were significantly elevated the day before all public
      holidays, with intoxication cases on the day of public holidays only higher on
      New Year's Day (ambulance 6.57, 95% confidence intervals (CI): 3.4-9.74; ED 3.34,
      95% CI: 1.28-5.4) and ANZAC Day (ambulance 3.71, 95% CI: 0.68-6.75). The
      Australian Football League (AFL) Grand Final (ED 2.37, 95% CI: 0.55-4.19),
      Commonwealth Games (ED 2.45, 95% CI: 0.6-4.3) and Melbourne Cup Day (ambulance
      6.14, 95% CI: 2.42-9.85) represented the sporting events with significant
      elevations in acute intoxication requiring medical attention. The last working
      day before Christmas was the only social event where a significant increase in
      acute intoxication occurred (ambulance 8.98, 95% CI: 6.8-11.15). CONCLUSIONS:
      Acute alcohol intoxication cases requiring ambulance, emergency department and
      hospital in-patient treatment increase substantially on the day preceding public
      holidays and other major social events.

PMID- 23134432
TI  - A de novo mutation in KIT causes white spotting in a subpopulation of German
      Shepherd dogs.
AB  - Although variation in the KIT gene is a common cause of white spotting among
      domesticated animals, KIT has not been implicated in the diverse white spotting
      observed in the dog. Here, we show that a loss-of-function mutation in KIT
      recapitulates the coat color phenotypes observed in other species. A spontaneous
      white spotting observed in a pedigree of German Shepherd dogs was mapped by
      linkage analysis to a single locus on CFA13 containing KIT (pairwise LOD = 15).
      DNA sequence analysis identified a novel 1-bp insertion in the second exon that
      co-segregated with the phenotype. The expected frameshift and resulting premature
      stop codons predicted a severely truncated c-Kit receptor with presumably
      abolished activity. No dogs homozygous for the mutation were recovered from
      multiple intercrosses (P = 0.01), suggesting the mutation is recessively
      embryonic lethal. These observations are consistent with the effects of null
      alleles of KIT in other species.

PMID- 23134434
TI  - From the Editor's desk.

PMID- 23134435
TI  - Editors' comments.

PMID- 23134436
TI  - A preterm infant with anaemia and left leg mild hemihypertrophy (discussion and
      diagnosis).

PMID- 23134437
TI  - 13-Cis retinoic acid can enhance the antitumor activity of non-replicating Sendai
      virus particle against neuroblastoma.
AB  - Hemagglutinating virus of Japan-envelope (HVJ-E) is a drug delivery vector based
      on inactivated Sendai virus. Recently, antitumor activities were found for HVJ-E
      itself and clinical trials of HVJ-E for some malignant tumors are now ongoing. We
      investigated the in vitro and in vivo antitumor effects of HVJ-E against
      neuroblastoma, which is one of the most common malignant solid tumors in
      childhood. The sensitivity of human neuroblastoma cell lines to HVJ-E correlated
      with the expression level of gangliosides, Sialylparagloboside (SPG) and GD1a,
      receptors for HVJ. Among the cell lines, SK-N-SH was the most sensitive to HVJ-E
      in vitro and total SPG and GD1a expression was the highest. Complete eradication
      of subcutaneous tumors derived from SK-N-SH cells was achieved by intratumoral
      injection of HVJ-E in SCID mice and no recurrence was observed for more than 300
      days after HVJ-E inoculation. In contrast, NB1 cells expressed the lowest amount
      of GD1a and SPG and were resistant to HVJ-E in vitro. The expression of GD1a
      increased by 13-cis retinoic acid (13cRA), which is a therapeutic drug for high
      risk neuroblastoma, thus leading to an improved sensitivity to HVJ-E in vitro.
      Only growth inhibition of the subcutaneous tumors derived from NB1 cells was
      achieved by HVJ-E in the SCID mice, but the combination of 13cRA and HVJ-E could
      achieve partial eradication of the xenograft and also lead to an improved
      prognosis. In conclusion, HVJ-E is a promising therapeutic modality for
      neuroblastoma and 13cRA can be used as an adjuvant to HVJ-E.

PMID- 23134438
TI  - Improving PCR detection of prey in molecular diet studies: importance of group
      specific primer set selection and extraction protocol performances.
AB  - While the morphological identification of prey remains in predators' faeces is
      the most commonly used method to study trophic interactions, many studies
      indicate that this method does not detect all consumed prey. Polymerase chain
      reaction-based methods are increasingly used to detect prey DNA in the predator
      food bolus and have proven efficient, delivering highly accurate results. When
      studying complex diet samples, the extraction of total DNA is a critical step, as
      polymerase chain reaction (PCR) inhibitors may be co-extracted. Another critical
      step involves a careful selection of suitable group-specific primer sets that
      should only amplify DNA from the targeted prey taxon. In this study, the food
      boluses of five Rattus rattus and seven Rattus exulans were analysed using both
      morphological and molecular methods. We tested a panel of 31 PCR primer pairs
      targeting bird, invertebrate and plant sequences; four of them were selected to
      be used as group-specific primer pairs in PCR protocols. The performances of four
      DNA extraction protocols (QIAamp((r))  DNA stool mini kit, DNeasy((r))  mericon
      food kit and two of cetyltrimethylammonium bromide-based methods) were compared
      using four variables: DNA concentration, A(260) /A(280)  absorbance ratio, food
      compartment analysed (stomach or faecal contents) and total number of prey
      specific PCR amplification per sample. Our results clearly indicate that the
      A(260) /A(280)  absorbance ratio, which varies between extraction protocols, is
      positively correlated to the number of PCR amplifications of each prey taxon. We
      recommend using the DNeasy((r))  mericon food kit (QIAGEN), which yielded results
      very similar to those achieved with the morphological approach.

PMID- 23134439
TI  - Leaf allocation patterns and 13C and 15N natural abundances of tropical lianas
      (Passiflora sp.) as dependent on external climbing support.
AB  - The transformation from self-supporting lianas to host-supported climbing lianas
      is related to re-allocation of biomass and nutrients among plant organs.
      Therefore, first, variations in leaf mass per area (LMA), leaf carbon and
      nitrogen allocation and (13)C and (15)N natural abundances were analysed among
      three tropical Passiflora species (P. edulis, P. ligularis, and P. tripartita) in
      a greenhouse study. Second, the influence of a climbing support was considered
      for each species and parameter. P. ligularis leaves were most enriched in (13)C
      in both treatments when compared with the other two species. This enrichment was
      caused by a high LMA, which is related to a high internal resistance to CO(2)
      diffusion. For P. edulis and P. tripartita, delta(13)C was additionally
      increasing with nitrogen content per area. Generally, there were no differences
      when considering carbon and nitrogen allocation to leaves of host-supported and
      self-supporting lianas. The only hints towards increased investment into leaves
      after the transition from self-supporting to host-supported stages could be seen
      by a trend to increased leaf areas and masses. delta(13)C values of supported P.
      edulis or P. tripartita plants were significantly increasing faster than those of
      non-supported plants once the interactions of leaf mass or nitrogen content per
      area were accounted for. Hence, the offer of a climbing support had only a minor
      impact on delta(13)C or delta(15)N values in vitro, but this could be different
      with increasing age of lianas in vivo.

PMID- 23134440
TI  - Masking and triggered unmasking of targeting ligands on liposomal chemotherapy
      selectively suppress tumor growth in vivo.
AB  - We investigated the feasibility and efficacy of a drug delivery strategy to
      vascularized cancer that combines targeting selectivity with high uptake by
      targeted cells and high bioexposure of cells to delivered chemotherapeutics.
      Targeted lipid vesicles composed of pH responsive membranes were designed to
      reversibly form phase-separated lipid domains, which are utilized to tune the
      vesicle's apparent functionality and permeability. During circulation, vesicles
      mask functional ligands and stably retain their contents. Upon extravasation in
      the tumor interstitium, ligand-labeled lipids become unmasked and segregated
      within lipid domains triggering targeting to cancer cells followed by
      internalization. In the acidic endosome, vesicles burst release the encapsulated
      therapeutics through leaky boundaries around the phase-separated lipid domains.
      The pH tunable vesicles contain doxorubicin and are labeled with an anti-HER2
      peptide. In vitro, anti-HER2 pH tunable vesicles release doxorubicin in a pH
      dependent manner, and exhibit 233% increase in binding to HER2-overexpressing
      BT474 breast cancer cells with lowering pH from 7.4 to 6.5 followed by
      significant (50%) internalization. In subcutaneous BT474 xenografts in nude mice,
      targeted pH tunable vesicles decrease tumor volumes by 159% relative to
      nontargeted vesicles, and they also exhibit better tumor control by 11% relative
      to targeted vesicles without an unmasking property. These results suggest the
      potential of pH tunable vesicles to ultimately control tumor growth at relatively
      lower administered doses.

PMID- 23134441
TI  - Laparoscopic total gastrectomy in gastric cancer: our experience in 92 cases.
AB  - INTRODUCTION: Laparoscopic total gastrectomy (LTG) is seldom used for gastric
      cancer because the complex vascularization and lymphatic drainage makes
      lymphadenectomy and esophagojejunal anastomosis difficult and requires special
      skills. Our aim was to demonstrate the feasibility and accuracy of LTG in gastric
      cancer with D2 lymphadenectomy. MATERIAL AND METHODS: Eighty-eight LTG and four
      laparoscopic remnant gastrectomies (LRGs) were performed over >12 years. The
      median patient age was 64 years, and the male/female ratio was 1.49/1. Eighty
      seven patients had a D2 and only five patients had a D1 lymphadenectomy. We
      propose the retrospective analysis of intra- and perioperative mortality and
      morbidity. RESULTS: In only four of 96 cases approached by laparoscopy, a
      conversion to laparotomy was needed. There were two (2.17%) perioperative deaths
      in 92 procedures and few complications. Histological data show 79 advanced
      gastric cancers (AGC), 11 early gastric cancers (EGC), and two gastric diffused
      lymphomas. The five-year Kaplan-Meier overall survival in patients with EGC and
      AGC was 100% and 58%, respectively. CONCLUSIONS: The results demonstrate the
      feasibility of an oncologically correct minimally invasive total gastrectomy. We
      would like to promote comparisons among different institutions to achieve better
      standardization of indications and techniques for a laparoscopic approach to
      gastric cancer.

PMID- 23134442
TI  - Evaluating the correlation between the HUESAD and OSATS scores: concurrent
      validity study.
AB  - BACKGROUND: The aim of this study was to determine whether a correlation exists
      between the HUESAD and both the OSATS checklist and the global rating score.
      MATERIAL AND METHODS: Fourteen participants were recruited, ranging from
      residents to consultants. The HUESAD measured three different parameters: Visual
      spatial ability, smoothness and accuracy. The OSTAS measured the endoscopic
      surgical skills by the checklist and the global rating score. RESULTS: A
      significant relationship was thus identified between the OSATS checklist (p <
      0.0001), the OSATS global rating score (p < 0.05) and the HUESAD assessment in
      the evaluation of visual-spatial ability. In terms of smoothness, there was also
      a significant relationship between the OSATS checklist (p < 0.05), the OSATS
      global rating score (p < 0.05) and the HUESAD assessment. Moreover, there was a
      significant relationship between the OSATS checklist (p < 0.05), the OSATS global
      rating score (p < 0.05) and the HUESAD assessment for accuracy. CONCLUSIONS:
      There was strong correlation between the motion analysis in the HUESAD assessment
      and OSATS checklist and the global rating score. Moreover, the visual spatial
      ability, smoothness and accuracy analyzed by the HUESAD were reliable parameters
      when assessing the endoscopic surgical skills.

PMID- 23134443
TI  - Endovascular treatment of iatrogenic aortic injury after spinal surgery.
AB  - A 59-year-old female presented to our institution with paraparesis caused by
      medullar compression secondary to multiple myeloma. Spinal cord decompression and
      transpedicular spine fixation were performed. A month later, the patient
      complained of sudden pain in her middle back. A CT scan revealed screw
      impingement on the aortic wall at T8 level. A thoracic stent-graft was deployed
      before removing the fixation. The patient had an uneventful postoperative course,
      without complications during the four-year follow-up. In this case report, stent
      graft placement proved to be safe and effective in avoiding bleeding during screw
      removal.

PMID- 23134444
TI  - An allergic phenotype and the use of steroid inhalers predict eosinophilic
      oesophagitis in patients with asthma.
AB  - BACKGROUND: Patients with eosinophilic oesophagitis (EoE) commonly have asthma
      and atopy. AIMS: To determine the predictive factors of EoE in patients with
      asthma. METHODS: A retrospective analysis of a large database identified 156
      asthma patients with EoE and 276 patients without EoE between 2000 and 2010.
      Clinical and laboratory characteristics were first analyzed in half of each
      group. Significant differences and modelling were then applied to the other half
      of each group in a split half analysis. RESULTS: Odds ratios and P-values found
      to predict the presence of EoE in asthma patients were: allergic vs. non-allergic
      asthma (4.07, <0.01), food allergies (45, <0.01), allergic rhinitis (2.13, =0.01)
      and peripheral eosinophilia (4.51, <0.01). The use of inhaled corticosteroids was
      negatively associated with EoE (0.41, <0.01) for asthma patients and (0.37, P <
      0.01) for allergic type asthma patients. EoE patients were also younger (27.4 vs.
      41.6 years old, P < 0.01). By logistic regression analysis, allergic asthma,
      presence of peripheral eosinophilia and use of inhaled steroids remained
      significant. From these parameters, a 3.5-point scoring system model for EoE in
      asthma was formed with an ROC = 0.787 on split analysis. CONCLUSIONS: In
      descending order, peripheral eosinophilia, allergic asthma and allergic rhinitis
      are associated with EoE in patients with asthma. Steroid inhalers appear to have
      a protective effect against EoE. An accurate and simple scoring system can be
      used as a screening tool to predict the presence of EoE in patients with asthma
      and dysphagia. EoE should be viewed as part of a generalised allergic phenotype
      rather than isolated oesophageal disease.

PMID- 23134445
TI  - Silica-lanthanum oxide: pioneer composite of rare-Earth metal oxide in selective
      phosphopeptides enrichment.
AB  - Relying on the successful journey of metal oxides in phosphoproteomics, lanthanum
      oxide is employed for the engineering of an affinity material for phosphopeptide
      enrichment. The lanthanum oxide is chemically modified on the surface of silica
      and characterized by scanning electron microscopy (SEM), energy-dispersive X-ray
      spectroscopy (EDX), and Fourier transform infrared spectroscopy (FTIR). The
      obtained silica-lanthanum oxide composite is applied for the selective enrichment
      of phosphopeptides from tryptic digest of standard protein (alpha-casein, beta
      casein, and commercially available casein mixtures from bovine milk). The
      enriched entities are analyzed by matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry (MALDI-TOF MS). The mass spectroscopy (MS)
      results show that the silica-lanthanum oxide composite exhibits enhanced
      capability for phosphopeptide enrichment with sensitivity assessed to be 50 fmol.
      Sequence coverage of casein is interpreted showing successful recovery. As a real
      sample, a protein digest of nonfat milk is applied. Also, the ability of
      lanthanum in different formats is checked in the selective phosphopeptides
      enrichment. The composite holds promising future in economic ground as it also
      possesses the regenerative ability for repetitive use.

PMID- 23134446
TI  - The associations between dietary intakes from 36 to 60 months of age and primary
      dentition non-cavitated caries and cavitated caries.
AB  - OBJECTIVE: To examine risk factors for non-cavitated caries, as well as cavitated
      caries. METHODS: Subjects were participants in the Iowa Fluoride Study cohort.
      Dietary data were collected at 36, 48, and 60 months old using 3-day dietary
      diaries, and a dental examination was conducted at about age 5. We compared the
      frequencies of dietary intakes of three groups: a) children having only d1 caries
      (n = 41); b) children having only cavitated (d2+f) caries (n = 46); and c)
      children having both d1 and d2+f caries (n = 49) with a forth group; d) those of
      caries-free children (n = 257). RESULTS: Multinomial and binomial logistic
      regression was used, where the categorical outcome was based on the 4 caries
      groups, and the caries-free group was designated as the reference. In the final
      model, sevenvariables were associated with the caries outcome. Lower milk
      consumption frequency at meals and greater presweetened cereal consumption
      frequency at meals were significantly associated with a greater likelihood of
      being in the d1 group. Greater regular soda pop consumption frequency and greater
      added sugar consumption frequency at snacks were significantly associated with
      being in the cavitated caries (d2+f and/or d1 d2+f) groups. Lower socioeconomic
      status and less frequent toothbrushing increased the likelihood of being in the
      d1 group. CONCLUSIONS: The results suggest that different food and beverage
      categories are associated with being in the d1 group compared with the cavitated
      caries groups. More frequent toothbrushing, greater milk consumption at meals,
      and avoiding presweetened cereal consumption at meals might reduce the risk of
      developing non-cavitated caries.

PMID- 23134447
TI  - New developments in endocervical glandular lesions.
AB  - McCluggage W G (2012) Histopathology New developments in endocervical glandular
      lesions There is evidence that the prevalence of premalignant and malignant
      endocervical glandular lesions is increasing in real as well as in apparent
      terms. In this review, new developments and selected controversial aspects of
      endocervical glandular lesions are covered, concentrating mainly on premalignant
      and malignant lesions. The terminology of premalignant endocervical glandular
      lesions is discussed with a comparison of the World Health Organization
      classification and the cervical glandular intraepithelial neoplasia (CGIN)
      system, which is in widespread use in the United Kingdom. Primary cervical
      adenocarcinomas comprise a heterogeneous group of different morphological types,
      and while it is known that the majority of these are associated with high-risk
      human papillomavirus (HPV), it has become clear in recent years that most of the
      more uncommon morphological types are unassociated with HPV, although they may
      sometimes be p16-positive. A spectrum of benign, premalignant and malignant
      cervical glandular lesions exhibiting gastric differentiation is now recognized;
      these include type A tunnel clusters, typical and atypical lobular endocervical
      glandular hyperplasia, adenoma malignum and gastric-type adenocarcinoma. The
      latter is a recently described variant of primary cervical adenocarcinoma which
      has a different morphological appearance to the usual endocervical type and which
      is probably associated with different patterns of spread and a worse prognosis.
      There is accumulating evidence that 'early invasive' cervical adenocarcinomas
      have an excellent prognosis and are suitable for conservative management.
      Immunohistochemical markers of value in the distinction between a primary
      cervical and endometrial adenocarcinoma are discussed. While it is well known
      that a panel of markers comprising oestrogen receptor (ER), vimentin, p16 and
      monoclonal carcinoembryonic antigen (CEA) is useful, several major pitfalls are
      pointed out and this panel of markers is predominantly of value in 'low-grade'
      adenocarcinomas. A related group of lesions, including cervical ectopic prostatic
      tissue and vaginal tubulosquamous polyp, are probably derived from para-urethral
      Skene's glands and may be positive with prostatic markers. Recent developments in
      cervical neuroendocrine neoplasms are discussed, as these are associated not
      uncommonly with a premalignant or malignant endocervical glandular lesion.

PMID- 23134448
TI  - Multiple lymphomatous polyposis of the gastrointestinal tract: report of three
      cases and literature review.

PMID- 23134449
TI  - Revised infant dietary recommendations: the impact of maternal education and
      other parental factors on adherence rates in Iceland.
AB  - AIM: Revised infant dietary recommendations from the Icelandic Nutrition Council
      (Nutrition: the first twelve months. Reykjavik, Iceland: The Icelandic Nutrition
      Council, 2003) are outlined in a booklet provided during free postnatal care.
      These focus on increasing the duration of exclusive and total breastfeeding and
      reducing cow's milk consumption. This study explored whether maternal education
      and other parental factors affected whether mothers followed the recommendations.
      METHODS: Mothers of randomly selected healthy infants (n = 200) completed
      questionnaires on body mass index (BMI), age, education (basic, medium and
      higher), household income, smoking and parental factors. Dietary data were
      collected during home visits by a researcher (0-4 months) and through monthly
      food records completed by parents or caregivers (5-12 months). RESULTS: Each
      maternal education level increased breastfeeding duration by 0.72 months (95% CI
      = 0.04, 1.39) and reduced cow's milk consumption by 36.7 mL/day (95% CI = -70.11,
      -3.03), when adjusted for maternal BMI, age, smoking and family income. Maternal
      education was not associated with duration of exclusive breastfeeding. Duration
      of exclusive and total breastfeeding was inversely associated with maternal BMI,
      B = -0.10 (95% CI = -0.16, -0.05) and -0.13 (95% CI = -0.23, -0.03),
      respectively. CONCLUSION: Mothers with higher education appear to have adapted
      more easily to the revised recommendations on infant diet, particularly when
      their infants are 6-12 months old. Higher maternal BMI was associated with
      shorter duration of both exclusive and total breastfeeding.

PMID- 23134450
TI  - Structural association of nonsteroidal anti-inflammatory drugs with lipid
      membranes.
AB  - The location and distribution of ibuprofen, a model nonsteroidal anti
      inflammatory drug, in a phospholipid bilayer was examined in molecular detail by
      a combination of neutron diffraction and computer simulations. In addition to
      their use as antipyretic, analgesic, and anti-inflammatory drugs, such
      nonsteroidal anti-inflammatory drugs are used in the treatment of a number of
      diseases including cancer and Alzheimer's. As a side effect, they have been known
      to cause gastrointestinal toxicity, although the molecular mechanism of their
      action is poorly understood. In this study, we have used contrast variation-based
      neutron diffraction to determine the position of the drug in a 1,2-dioleoyl-sn
      glycero-3-phosphatidylcholine lipid bilayer and explore changes to the bilayer
      structure upon drug incorporation. In its charged state, the drug was found to
      locate in the polar headgroup region of the phospholipid bilayer, to induce
      bilayer thinning, and to increase the number of water molecules closely
      associated with the bilayer. These structural insights are consistent with
      molecular dynamics simulations and earlier macroscopic experiments of vesicle
      structure and dynamics. Using MD simulations, the neutral ibuprofen, typically
      observed at low pH and inaccessible to the diffraction studies, was found to
      locate deeper within the bilayer than the charged form.

PMID- 23134451
TI  - In search of cathepsins: how reovirus enters host cells.

PMID- 23134452
TI  - Asymmetric and frequency-dependent pollinator-mediated interactions may influence
      competitive displacement in two vernal pool plants.
AB  - A plant species immigrating into a community may experience a rarity disadvantage
      due to competition for the services of pollinators. These negative reproductive
      interactions have the potential to lead to competitive displacement or exclusion
      of a species from a site. In this study, we used one- and two-species arrays of
      potted plants to test for density and frequency dependence in pollinator-mediated
      and above-ground intraspecific and interspecific competition between two species
      of Limnanthes that have overlapping ranges, but rarely occur in close sympatry.
      There were asymmetric competitive effects; the species responded differently to
      their frequency within 16-plant replacement series arrays. Limnanthes douglasii
      rosea experienced stronger reductions in lifetime and per-flower fertility,
      likely due to pollinator-mediated competition with Limnanthes alba. This effect
      may be linked to asymmetrical competition through heterospecific pollen transfer.
      This study demonstrates that pollinator-mediated competition may discourage
      establishment of L. d. rosea in sites already occupied by its congener.

PMID- 23134453
TI  - Elimination kinetics of domoic acid from the brain and cerebrospinal fluid of the
      pregnant rat.
AB  - Domoic acid (DA) causes neurological effects in multiple species upon exposure,
      including status epilepticus in pregnant sea lions and an epileptic disease state
      that commonly develops in juveniles. This study aims to define brain
      toxicokinetic parameters in the pregnant rat in the larger context of maternal
      fetal toxin transfer. Specifically, Sprague-Dawley rats were exposed to a low
      observable effect level of 1.0 mg DA/kg intravenously at gestational day 20, and
      plasma, brain, and cerebrospinal fluid (CSF) samples were taken at discrete time
      points over 24 h. Domoic acid concentrations were determined by a tandem LC/MS
      method recently optimized for brain tissue and CSF. Data showed that 6.6% of
      plasma DA reached the brain, 5.3% reached the CSF, and DA levels were nearly
      identical in both brain and CSF for 12 h, remaining above the threshold to
      activate isolated hippocampal neurons for 2 h. The calculated terminal half-life
      of CSF was 4 h, consistent with the time for complete CSF regeneration,
      suggesting that CSF acts as a mechanism to clear DA from the brain.

PMID- 23134456
TI  - Murray and Jackson reply.

PMID- 23134457
TI  - Adaptive autobiographical memory in younger and older adults: the indirect
      association of integrative and instrumental reminiscence with depressive
      symptoms.
AB  - Despite the established effectiveness of reminiscence-based interventions for
      depression, little research exists into the pathways through which specific
      reminiscence functions are related to depressive symptoms. Drawing on theory of
      the mechanisms of change in cognitive-reminiscence therapy, the current study
      tests the hypothesised indirect associations of adaptive integrative and
      instrumental reminiscence functions with depressive symptoms and whether these
      relationships might differ among younger and older adults. Questionnaires were
      completed by a large community sample of the Australian population. Multiple
      mediation models were tested in two groups: younger adults (n = 730, M age =
      52.24, SD=9.84) and older adults (n = 725, M age= 73.59, SD=6.29). Results were
      consistent across age groups, indicating that there was direct relationship
      between these reminiscence functions and depressive symptoms, but that
      integrative reminiscence is indirectly associated with depressive symptoms
      through meaning in life, self-esteem, and optimism, and that instrumental
      reminiscence is indirectly associated with depressive symptoms through primary
      control and self-efficacy. This study provides support for the relationships
      between constructs underlying the proposed mechanisms of change in cognitive
      reminiscence therapy for the treatment of depression, and suggests these
      relationships are similar for younger and older adults.

PMID- 23134458
TI  - Antithrombotic effect of chikusetsusaponin IVa isolated from Ilex paraguariensis
      (Mate).
AB  - The triterpene chikusetsusaponin IVa was isolated from the fruit of Ilex
      paraguariensis. Using biochemical and pharmacological methods, we demonstrated
      that chikusetsusaponin IVa (1) prolongs the recalcification time, prothrombin
      time, activated partial thromboplastin time, and thrombin time of normal human
      plasma in a dose-dependent manner, (2) inhibits the amidolytic activity of
      thrombin and factor Xa upon synthetic substrates S2238 and S2222, (3) inhibits
      thrombin-induced fibrinogen clotting (50% inhibition concentration, 199.4 +/- 9.1
      MUM), and (4) inhibits thrombin- and collagen-induced platelet aggregation. The
      results also indicate that chikusetsusaponin IVa preferentially inhibits thrombin
      in a competitive manner (K(i)=219.6 MUM). Furthermore, when administered
      intravenously to rats, chikusetsusaponin IVa inhibited thrombus formation in a
      stasis model of venous thrombosis, although it did not induce a significant
      bleeding effect. Chikusetsusaponin IVa also prolonged the ex vivo activated
      partial thromboplastin time. Altogether, these data suggest that
      chikusetsusaponin IVa exerts antithrombotic effects, including minor hemorrhagic
      events. This appears to be important for the development of new therapeutic
      agents.

PMID- 23134459
TI  - Antiamnesic effects of ethyl acetate fraction from chestnut (Castanea crenata
      var. dulcis) inner skin on Abeta(25-35)-induced cognitive deficits in mice.
AB  - To investigate neuronal cell protective effects of an ethyl acetate fraction from
      chestnut inner skin, in vitro assays, including 2',7'-dichlorofluorescein
      diacetate, 3-[4,5-dimethythiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT),
      and lactate dehydrogenase (LDH), were performed. Intracellular accumulation of
      reactive oxygen species resulting from hydrogen peroxide (H(2)O(2)) treatment of
      PC12 cells was significantly reduced when ethyl acetate fractions were present in
      the medium compared to PC12 cells treated with H(2)O(2) only. In a cell viability
      assay using MTT, the ethyl acetate fraction protected against H(2)O(2)-induced
      neurotoxicity, and inhibited LDH release into the medium. In addition, the ethyl
      acetate fraction improved in vivo cognitive ability against amyloid beta-peptide
      (Abeta)-induced neuronal deficit. High-performance liquid chromatography analyses
      showed that gallic acid, catechin, and epicatechin were predominant phenolics in
      the ethyl acetate fraction. Consequently, the results suggest that chestnut inner
      skin, including above phenolics, could ameliorate Abeta-induced learning and
      memory deficiency, and be utilized as effective substances for neurodegenerative
      disorders, notably Alzheimer's disease.

PMID- 23134460
TI  - Relationship between total phenolic content, antioxidant potential, and
      antiglycation abilities of common culinary herbs and spices.
AB  - Advanced glycation endproducts and oxidative stress contribute to the
      pathogenesis of diabetic complications. The total phenolic content (TPC),
      antioxidant, and antiglycation properties of crude ethanolic extracts of 10
      common culinary herbs and spices from Mauritius were investigated in vitro.
      Fluorescence at 370 nm/440 nm was used as an index of albumin glycation. Allium
      sativum had the highest TPC (3.1 mg GAE/mL), whereas Allium cepa L. showed the
      highest radical scavenging capacity (72%) and Zingiber officinale had the most
      potent ferric-reducing antioxidant power (FRAP; 2.99 mg AAE/mL). In contrast,
      Thymus vulgaris and Petroselinum crispum had the most potent antiglycation
      activity with IC(50) values of 21.8 and 200 mg/mL, respectively. There was no
      significant correlation between TPC (r=0.001), FRAP (r=0.161), and the
      antiglycation activity (r=0.034) for the extracts studied. Therefore, the results
      showed that antiglycation properties of plant-derived extracts cannot always be
      attributed to their phenolic content or antioxidant potential.

PMID- 23134461
TI  - Antibacterial activity of Greek and Cypriot honeys against Staphylococcus aureus
      and Pseudomonas aeruginosa in comparison to manuka honey.
AB  - The antibacterial activity of 31 Greek and Cypriot honeys against Staphylococcus
      aureus and Pseudomonas aeruginosa was initially screened using an agar-well
      diffusion assay in comparison with manuka honey. The minimum inhibitory
      concentration (MIC) was determined in broth using a spectrophotometric-based
      assay. The MIC of treated honeys with catalase or proteinase K was determined and
      compared with those of untreated honeys. All tested honeys demonstrated
      antibacterial activity against S. aureus on agar-well diffusion assay. MICs of
      tested honeys were determined as 3.125-25% (v/v), compared with manuka honey at
      6.25% (v/v). Similarly, 21 of 31 tested honeys demonstrated antibacterial
      activity on agar-well diffusion assay against P. aeruginosa. Their MICs ranged
      from 6.25% to 25% (v/v) compared with 12.5% (v/v) for manuka honey. Antibacterial
      activity of tested honeys could be largely attributed to hydrogen peroxide
      formation and in some cases to unidentified proteinaceous compounds. In
      conclusion, Greek and Cypriot honeys demonstrated significant but variable
      antibacterial activity against P. aeruginosa and especially S. aureus. To the
      best of our knowledge this is the first study that has thoroughly examined the
      antibacterial activity of Greek and Cypriot honeys compared with manuka honey.
      The high antibacterial activity exerted by some tested honeys warrants further
      investigation.

PMID- 23134462
TI  - Phycocyanin induces apoptosis and enhances the effect of topotecan on prostate
      cell line LNCaP.
AB  - C-phycocyanin (C-PC) from Spirulina has been previously shown to have anticancer
      properties. Here, we report on anticancer activity of C-PC that was isolated from
      the novel cyanobacterium Limnothrix sp. 37-2-1. C-PC from this organism exhibited
      anticancer properties in our in vitro systems; however, the required doses were
      well above the range of anticancer drugs normally used. Therefore, we conducted
      several experiments to test whether lower-than-usual doses of the anticancer drug
      topotecan (TPT) can offer the same level of cytotoxic effects as normal doses
      when combined with C-PC. For this purpose, cytotoxicities of C-PC and TPT were
      tested using the LNCaP (prostate cancer) cells. We found that when only 10% of a
      typical dose of TPT was combined with C-PC, the cancer cells were killed at a
      higher rate than when TPT was used alone at full dose. Similarly, we were also
      able to detect an increased level of radical oxygen species (ROS) generation as
      well as an increase in activities of caspase-9 and caspase-3 when these two
      compounds were used in combination. Taken together, our findings suggest that
      combining C-PC from Limnothrix sp. with the lower dose of TPT can induce
      apoptosis through generation of ROS and activation of caspases. In that respect,
      we suggest that C-PC can potentially improve the efficacy of the currently
      available anticancer drug, and therefore diminish its harsh side effects in the
      patient.

PMID- 23134463
TI  - Spirulina (arthrospira) protects against valproic acid-induced neural tube
      defects in mice.
AB  - Valproic acid (VPA) is a potent inducer of neural tube defects in human and
      mouse, its teratogenicity is associated with its potential to generation of free
      radicals and increase oxidative stress. Furthermore, spirulina (SP) has shown
      pharmacological properties against teratogenicity, which are attributed to its
      antioxidant potential. Accordingly, the present study was performed to
      investigate the influence of SP on the teratogenicity of VPA in imprinting
      control region mice and the possible mechanisms of action. VPA (sodium valproate)
      was administered intraperitoneally to mice on gestation day (GD) 8 at a dose of
      600 mg/kg. SP was given orally at 125, 250, and 500 mg/kg daily from GD0 through
      GD18. The most common finding in fetuses with VPA exposure was exencephaly. SP
      decreased the incidence of this and other malformations and increased levels of
      superoxide dismutase, catalase, and glutathione peroxidase. In conclusion, these
      results illustrate the protective action of SP through its antioxidant activity
      against VPA-induced teratogenicity.

PMID- 23134464
TI  - Induction of a T-Helper 1 (Th1) immune response in mice by an extract from the
      Pleurotus eryngii (Eringi) mushroom.
AB  - To assess the effect of edible mushroom extracts on the induction of T-helper 1
      (Th1) immunity, we examined differences in interferon-gamma (IFN-gamma) and
      interleukin (IL)-4 production in mice induced by hot-water extracts of 15 species
      of edible mushroom. Extracts from Agaricus bisporus, Flammulina velutipes,
      Hypsizigus marmoreus, Lentinula edodes, and Lyophyllum decastes induced both IFN
      gamma and IL-4 production in mice, whereas extracts from Pleurotus ostreatus only
      induced IL-4. In contrast, extracts from Agaricus blazei, Grifola frondosa,
      Morchella esculenta, Pholiota nameko, Pleurotus citrinopileatus, and Pleurotus
      eryngii induced only IFN-gamma production. In particular, the extract from P.
      eryngii induced high levels of IFN-gamma and reduced levels of IL-4. We further
      investigated the use of a trial immunogen using the P. eryngii extract as a Th1
      immunostimulator. An oil-in-water emulsion of the hot-water extract from P.
      eryngii (immunostimulator) and ovalbumin (OVA; antigen) was used as a trial
      immunogen. This immunogen induced strong OVA-specific IgG2a antibody production
      in mice compared with the negative controls. In addition, OVA-specific IgG1
      antibody levels were lower than those for the negative controls. Marked increases
      in serum IFN-gamma levels and high-level production of IFN-gamma in the culture
      supernatant from the CD4(+) spleen cells in the trial immunogen group mice were
      observed. Our results suggested that the hot-water extract from P. eryngii
      induced Th1 immunity by acting as an immunostimulator.

PMID- 23134467
TI  - Association between epileptiform discharges and the sleep cycle in 200 epileptic
      patients.
AB  - OBJECTIVE: The poor sleep quality of epileptic patients may be partly due to the
      occurrence epileptiform discharges (EDs). We observed the number of interictal
      discharges in each sleep stage and explored the associations between EDs and
      sleep phases in epileptic patients. METHODS: Two hundred epileptic patients and
      182 healthy volunteers were enrolled in the current study. For all subjects,
      video electroencephalography (EEG) monitoring and 24-hr night polysomnography
      were conducted to detect EDs and analyze the sleep structures. RESULTS: EDs were
      detected in 91% of epileptic patients with the most frequent cases from the
      temporal lobe. The EDs detected during waking, sleeping, or both waking and
      nonrapid eye movement (NREM) sleep stages 1-2 accounted for 7.1%, 19.2%, and
      25.3% of the total patients, respectively. EDs were rare during NREM stages 3-4
      with 1.1% of total patients mainly in the central-temporal lobe. The total sleep
      time and time spent in REM were similar between the epileptic patients and
      healthy volunteers. However, epileptic patients spent a significantly longer mean
      sleep time in NREM stages 1-2 (293.91 +/- 27.57 min vs. 223.17 +/-15.28; p =
      .000) and less in NREM stages 3-4 (50.11 +/- 12.12 min vs. 133.96 +/- 10.77; p =
      .000) than healthy volunteers. Furthermore, asymmetric sleep spindles and
      fragmentary sleep structure as well as high inversion frequency were found in
      26.7% and 43.3% of epileptic patients, respectively. CONCLUSION: Combination of
      long-term video EEG with polysomnography is a useful method to analyze
      associations between EDs and the sleep-wake cycle. This strategy can also help
      identify the nature of sleep disorders in epileptic patients, which may improve
      the treatment efficacy.

PMID- 23134465
TI  - A shift in microglial beta-amyloid binding in Alzheimer's disease is associated
      with cerebral amyloid angiopathy.
AB  - Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) are two common
      pathologies associated with beta-amyloid (Abeta) accumulation and inflammation in
      the brain; neither is well understood. The objective of this study was to
      evaluate human post-mortem brains from AD subjects with purely parenchymal
      pathology, and those with concomitant CAA (and age-matched controls) for
      differential expression of microglia-associated Abeta ligands thought to mediate
      Abeta clearance and the association of these receptors with complement
      activation. Homogenates of brain parenchyma and enriched microvessel fractions
      from occipital cortex were probed for levels of C3b, membrane attack complex
      (MAC), CD11b and alpha-2-macroglobulin and immunoprecipitation was used to
      immunoprecipitate (IP) CD11b complexed with C3b and Abeta. Both C3b and MAC were
      significantly increased in CAA compared to AD-only and controls and IP showed
      significantly increased CD11b/C3b complexes with Abeta in AD/CAA subjects.
      Confocal microscopy was used to visualize these interactions. MAC was remarkably
      associated with CAA-affected blood vessels compared to AD-only and control
      vessels. These findings are consistent with an Abeta clearance mechanism via
      microglial CD11b that delivers Abeta and C3b to blood vessels in AD/CAA, which
      leads to Abeta deposition and propagation of complement to the cytolytic MAC,
      possibly leading to vascular fragility.

PMID- 23134468
TI  - Synthesis and reactions of the first room temperature stable Li/Cl
      phosphinidenoid complex.
AB  - P-Trityl substituted Li/Cl phosphinidenoid tungsten(0) complex (OC)5W{Ph3CP(Li/12
      crown-4)Cl} (3) was prepared via chlorine/lithium exchange in complex
      (OC)5W{Ph3CPCl2} (2) using (t)BuLi in the presence of 12-crown-4 in
      tetrahydrofuran (THF) at low temperature; complex 3 possesses significantly
      increased thermal stability in contrast to previously reported analogue
      derivatives. Terminal phosphinidene-like reactivity of 3 was used in reactions
      with benzaldehyde and isopropyl alcohol as oxaphosphirane complex
      (OC)5W{Ph3CPC(Ph)O} (5) and phosphinite complex (OC)5W{Ph3CP(H)O(i)Pr} (6) were
      obtained selectively. Reaction of 3 with phosgene allowed to obtain the first
      kinetically stabilized chloroformylphosphane complex (OC)5W{Ph3CP(Cl)C(O)Cl} (4).
      Density functional theory (DFT) calculations revealed remarkable differences in
      the degree of P-Li bond dissociation 3a-d: using a continuum model 3 displays a
      covalent character of P-Li bond (COSMO (THF)) (a), which becomes elongated if 12
      crown-4 is coordinated to lithium (b) and is cleaved if a dimethylether unit is
      additionally coordinated to lithium (c). A similar result was obtained for the
      case of 3(thf)4 in which also a solvent-separated ion pair structure is present
      (d). All products were unambiguously characterized by various spectroscopic means
      and, in the case of 2 and 4-6, by single-crystal X-ray diffraction analysis. In
      all structures very long P-C bonds were determined being in the range from 1.896
      to 1.955 A. 

PMID- 23134469
TI  - Positive selection in the major histocompatibility complex class III region of
      cynomolgus macaques (Macaca fascicularis) of the Philippines origin.
AB  - The cynomolgus macaque (Macaca fascicularis) is a model of choice among primates
      for the study of local adaptation processes because of its mixed and wide insular
      and continental distribution. In a previous study, by using 12 markers [5
      microsatellites located in the major histocompatibility complex (MHC) region and
      7 outside MHC], we have detected a signal of positive selection on the
      microsatellite DRACA located inside the gene DRA. In order to refine the location
      of this signal of positive selection in the MHC region, we studied the genetic
      diversity of 36 markers (18 microsatellites spread across the MHC region and 18
      autosomal microsatellites outside MHC) in a sample of 254 individuals from four
      populations (Vietnam, Java, the Philippines, and Mauritius). We estimated for
      each locus the deviation of F(st) from a neutral model by using two methods based
      on contrasted demographic models. The two approaches showed a signal of positive
      selection in the MHC class III region that is much more significant than the one
      previously reported for the marker DRACA which could have been influenced by a
      hitchhiking effect due to its proximity with the class III region.

PMID- 23134470
TI  - Randomised clinical trial: comparison of two everolimus dosing schedules in
      patients with advanced hepatocellular carcinoma.
AB  - BACKGROUND: Deregulation of mammalian target of rapamycin (mTOR) signalling is
      common in human hepatocellular carcinoma (HCC). AIM: To determine the maximum
      tolerated dose (MTD) of the oral mTOR inhibitor everolimus in advanced HCC
      patients. METHODS: Patients with locally advanced or metastatic HCC (Child-Pugh
      class A or B) were enrolled in an open-label phase 1 study and randomly assigned
      to daily (2.5-10 mg) or weekly (20-70 mg) everolimus in a standard 3 + 3 dose
      escalation design. MTD was based on the rate of dose-limiting toxicities (DLTs).
      Secondary endpoints included safety, pharmacokinetics and tumour response. In a
      post hoc analysis, serum hepatitis B virus (HBV) DNA levels were quantified.
      RESULTS: Thirty-nine patients were enrolled. DLTs occurred in five of 21 patients
      in the daily and two of 19 patients in the weekly cohort. Daily and weekly MTDs
      were 7.5 mg and 70 mg respectively. Grade 3/4 adverse events with a >=10%
      incidence were thrombocytopenia, hypophosphataemia and alanine transaminase (ALT)
      elevation. In four hepatitis B surface antigen (HBsAg)-seropositive patients,
      grade 3/4 ALT elevations were accompanied by significant (>1 log) increases in
      serum HBV levels. The incidence of hepatitis flare (defined as ALT increase >100
      IU/mL from baseline) in HBsAg-seropositive patients with and without detectable
      serum HBV DNA before treatment was 46.2% and 7.1% respectively (P < 0.01, Fisher
      exact test). Disease control rates in the daily and weekly cohorts were 71.4% and
      44.4% respectively. CONCLUSIONS: The recommended everolimus dosing schedule for
      future hepatocellular carcinoma studies is 7.5 mg daily. Prophylactic anti-viral
      therapy should be mandatory for HBsAg-seropositive patients (ClinicalTrials.gov
      NCT00390195).

PMID- 23134471
TI  - What every conservation biologist should know about human population.

PMID- 23134473
TI  - Solid pseudopapillary neoplasm of the pancreas with prominent atypical
      multinucleated giant tumour cells.
AB  - AIMS: Solid pseudopapillary neoplasm of the pancreas (SPN) is a rare low-grade
      malignant neoplasm. To our knowledge, SPN with prominent atypical multinucleated
      giant tumour cells (MNGTCs) has not yet been reported. METHODS AND RESULTS: We
      identified four cases of SPN with prominent atypical MNGTCs in a cohort of 62
      cases of SPN (6.5%). The MNGTCs contained multiple enlarged, hyperchromatic,
      irregular nuclei with ample eosinophilic cytoplasm, typically present in the
      solid area of the tumour. The MNGTCs had an immunohistochemical profile typical
      of the conventional SPN and were positive for vimentin, beta-catenin, CD10 and
      progesterone receptor, but negative for pan-cytokeratin, chromogranin,
      synaptophysin, trypsin, Ki-67 and CD68 in all four cases. Patients of SPN with
      prominent MNGTCs were older than those with conventional SPN (P = 0.01); tumours
      were discovered incidentally by imaging studies for an unrelated disease in all
      four cases, and with a female to male ratio of 1:1. The proliferation index (Ki
      67) was <1% in all four cases. None of the three patients for whom information
      was available developed recurrence during follow-up of 2.7, 3.8 and 5.0 years.
      CONCLUSIONS: The presence of MNGTCs in SPN most probably represents degenerative
      change of the tumour cells and does not seem to affect the prognosis.

PMID- 23134474
TI  - Structure of indole...imidazole heterodimer in a supersonic jet: a gas phase
      study on the interaction between the aromatic side chains of tryptophan and
      histidine residues in proteins.
AB  - In this study, we have investigated the binding motifs between the aromatic side
      chains of tryptophan and histidine residues in proteins by studying the
      indole...imidazole heterodimer in a supersonic jet. Different spectroscopic
      techniques including resonant two-photon ionization (R2PI), UV-UV hole-burning,
      and resonant ion dip infrared (RIDIR) spectroscopy merged with quantum chemistry
      calculations have been used for this work. UV-UV hole-burning spectroscopy has
      been used to confirm the presence of only one structure of the dimer in the
      experiment. From the comparison of the RIDIR spectrum of the observed dimer with
      the theoretical IR spectra of different structures of the dimer, it is found that
      the dimer present in the experiment has a V-shaped structure held by N-H...N
      hydrogen bond, C-H...pi, and weakly present pi...pi stacking interactions. The
      most important finding of the present study is that the noncovalent interactions
      present in the observed dimer have a close resemblance with those present between
      tryptophan and histidine residues in a nonfluorescent flavoprotein. The present
      spectroscopic investigation on the indole...imidazole dimer has also immense
      pharmaceutical significance as this imparts molecular level understanding about
      the binding motifs of the imidazole drugs with the indole chromophore present in
      proteins.

PMID- 23134475
TI  - Two highly validated SSR multiplexes (8-plex) for Euphrates' poplar, Populus
      euphratica (Salicaceae).
AB  - Multiplex PCR amplification of microsatellites has significantly increased the
      throughput and decreased the costs of genotyping. We have developed two highly
      polymorphic microsatellite multiplexes for Populus euphratica, the only tree
      species found in desert regions of Western China and adjacent Central Asian
      countries. The first of these multiplex kits comprises an eight-Plex of genomic
      SSRs (gSSRs) obtained from published databases. The second comprises an eight
      plex of newly designed EST-SSRs (eSSRs) based on expressed sequence tags for P.
      euphratica. Both kits were tested on a sample of 170 individuals from four
      populations. The gSSRs exhibited slightly more polymorphism than the eSSRs. The
      new multiplex protocols yielded consistent results in the hands of multiple
      researchers, demonstrating their robustness. The 16 loci used in the kits
      exhibited a high transferability rate (82.0%) in eight other poplar species
      belonging to five different sections of the genus. Both kits should therefore be
      useful for further investigations of population genetics in P. euphratica and
      related species. Our results indicate that it is essential to follow recently
      established recommendations when developing microsatellite markers, including
      verifying the amplification efficiency, detecting null alleles and carefully
      measuring error rates.

PMID- 23134477
TI  - Vitamin D receptor BsmI polymorphism and osteoporosis risk: a meta-analysis from
      26 studies.
AB  - OBJECTIVE: Growing evidence has shown that vitamin D deficiency can cause lower
      bone mineral density (BMD) and an increased risk of osteoporosis. Vitamin D
      receptor (VDR) BsmI polymorphism (rs1544410) can affect BMD variation and
      circulating osteocalcin levels. To date, a wide range of epidemiological studies
      have been carried out to evaluate the association between VDR BsmI polymorphism
      and susceptibility to osteoporosis. Conflicting results, however, were obtained.
      The aim of this study was to evaluate the effect of VDR BsmI polymorphism on
      osteoporosis risk using a meta-analysis. METHODS: Twenty-six publications were
      identified by searching PubMed and Embase databases. The association between VDR
      BsmI polymorphism and osteoporosis was estimated by calculating pooled odds
      ratios (ORs) with corresponding 95% confidence intervals (CIs). RESULTS: The bb
      genotype was associated with a significantly decreased risk of osteoporosis in
      overall comparison (bb vs. BB: OR=0.61, 95% CI, 0.40-0.92; bb vs. BB/Bb: OR=0.70,
      95% CI, 0.52-0.95, respectively). Subgroup analyses showed that the bb genotype
      had a decreased risk of developing osteoporosis in postmenopausal women (bb vs.
      BB/Bb: OR=0.68, 95% CI, 0.46-0.98) and Africans (Bb/bb vs. BB: OR=0.18, 95% CI,
      0.09-0.37). CONCLUSION: The VDR BsmI polymorphism may have a protective role
      against the development of osteoporosis.

PMID- 23134476
TI  - Immunohistological and electrophysiological evidence that N
      acetylaspartylglutamate is a co-transmitter at the vertebrate neuromuscular
      junction.
AB  - Immunohistochemical studies previously revealed the presence of the peptide
      transmitter N-acetylaspartylglutamate (NAAG) in spinal motor neurons, axons and
      presumptive neuromuscular junctions (NMJs). At synapses in the central nervous
      system, NAAG has been shown to activate the type 3 metabotropic glutamate
      receptor (mGluR3) and is inactivated by an extracellular peptidase, glutamate
      carboxypeptidase II. The present study tested the hypothesis that NAAG meets the
      criteria for classification as a co-transmitter at the vertebrate NMJ. Confocal
      microscopy confirmed the presence of NAAG immunoreactivity and extended the
      resolution of the peptide's location in the lizard (Anolis carolinensis) NMJ.
      NAAG was localised to a presynaptic region immediately adjacent to postsynaptic
      acetylcholine receptors. NAAG was depleted by potassium-induced depolarisation
      and by electrical stimulation of motor axons. The NAAG receptor, mGluR3, was
      localised to the presynaptic terminal consistent with NAAG's demonstrated role as
      a regulator of synaptic release at central synapses. In contrast, glutamate
      receptors, type 2 metabotropic glutamate receptor (mGluR2) and N-methyl-d
      aspartate, were closely associated with acetylcholine receptors in the
      postsynaptic membrane. Glutamate carboxypeptidase II, the NAAG-inactivating
      enzyme, was identified exclusively in perisynaptic glial cells. This localisation
      was confirmed by the loss of immunoreactivity when these cells were selectively
      eliminated. Finally, electrophysiological studies showed that exogenous NAAG
      inhibited evoked neurotransmitter release by activating a group II metabotropic
      glutamate receptor (mGluR2 or mGluR3). Collectively, these data support the
      conclusion that NAAG is a co-transmitter at the vertebrate NMJ.

PMID- 23134478
TI  - How to differentiate non-erosive reflux disease from functional heartburn.
AB  - Heartburn is a common symptom in gastroesophageal reflux disease. Endoscopic
      examination can differentiate between reflux esophagitis and non-erosive reflux
      disease (NERD), but not between NERD and functional heartburn. With the
      development of new techniques, more NERD patients could be identified among those
      previously diagnosed with functional heartburn. Most patients with NERD, however,
      could be identified based on their clinical characteristics and response to
      proton pump inhibitors and/or integrated anti-gastroesophageal reflux therapy.

PMID- 23134479
TI  - Use of micro-computed tomography to nondestructively characterize biomineral
      coatings on solid freeform fabricated poly (L-lactic acid) and poly ((epsilon
      caprolactone) scaffolds in vitro and in vivo.
AB  - Biomineral coatings have been extensively used to enhance the osteoconductivity
      of polymeric scaffolds. Numerous porous scaffolds have previously been coated
      with a bone-like apatite mineral through incubation in simulated body fluid
      (SBF). However, characterization of the mineral layer formed on scaffolds,
      including the amount of mineral within the scaffolds, often requires destructive
      methods. We have developed a method using micro-computed tomography (MU-CT)
      scanning to nondestructively quantify the amount of mineral in vitro and in vivo
      on biodegradable scaffolds made of poly (L-lactic acid) (PLLA) and poly (epsilon
      caprolactone) (PCL). PLLA and PCL scaffolds were fabricated using an indirect
      solid freeform fabrication (SFF) technique to achieve orthogonally interconnected
      pore architectures. Biomineral coatings were formed on the fabricated PLLA and
      PCL scaffolds after incubation in modified SBF (mSBF). Scanning electron
      microscopy and X-ray diffraction confirmed the formation of an apatite-like
      mineral. The scaffolds were implanted into mouse ectopic sites for 3 and 10
      weeks. The presence of a biomineral coating within the porous scaffolds was
      confirmed through plastic embedding and MU-CT techniques. Tissue mineral content
      (TMC) and volume of mineral on the scaffold surfaces detected by MU-CT had a
      strong correlation with the amount of calcium measured by the
      orthocresolphthalein complex-one (OCPC) method before and after implantation.
      There was a strong correlation between OCPC pre- and postimplantation and MU-CT
      measured TMC (R(2)=0.96 preimplant; R(2)=0.90 postimplant) and mineral volume
      (R(2)=0.96 preimplant; R(2)=0.89 postimplant). The MU-CT technique showed
      increases in mineral following implantation, suggesting that MU-CT can be used to
      nondestructively determine the amount of calcium on coated scaffolds.

PMID- 23134480
TI  - Conditional requirement for exopolysaccharide in the Mesorhizobium-Lotus
      symbiosis.
AB  - Rhizobial surface polysaccharides are required for nodule formation on the roots
      of at least some legumes but the mechanisms by which they act are yet to be
      determined. As a first step to investigate the function of exopolysaccharide
      (EPS) in the formation of determinate nodules, we isolated Mesorhizobium loti
      mutants affected in various steps of EPS biosynthesis and characterized their
      symbiotic phenotypes on two Lotus spp. The wild-type M. loti R7A produced both
      high molecular weight EPS and lower molecular weight (LMW) polysaccharide
      fractions whereas most mutant strains produced only LMW fractions. Mutants
      affected in predicted early biosynthetic steps (e.g., exoB) formed nitrogen
      fixing nodules on Lotus corniculatus and L. japonicus 'Gifu', whereas mutants
      affected in mid or late biosynthetic steps (e.g., exoU) induced uninfected nodule
      primordia and, occasionally, a few infected nodules following a lengthy delay.
      These mutants were disrupted at the stage of infection thread (IT) development.
      Symbiotically defective EPS and Nod factor mutants functionally complemented each
      other in co-inoculation experiments. The majority of full-length IT observed
      harbored only the EPS mutant strain and did not show bacterial release, whereas
      the nitrogen-fixing nodules contained both mutants. Examination of the symbiotic
      proficiency of the exoU mutant on various L. japonicus ecotypes revealed that
      both host and environmental factors were linked to the requirement for EPS. These
      results reveal a complex function for M. loti EPS in determinate nodule formation
      and suggest that EPS plays a signaling role at the stages of both IT initiation
      and bacterial release.

PMID- 23134481
TI  - MicroRNA9 regulates neural stem cell differentiation by controlling Hes1
      expression dynamics in the developing brain.
AB  - Earlier studies show that Hes1 expression is oscillatory in neural stem cells but
      sustained and high in the roof plate and the floor plate, and that such different
      dynamics of Hes1 expression (oscillatory versus sustained) regulate different
      proliferation and differentiation characteristics of these cells (active in
      neural stem cells but rather dormant in roof/floor plate cells). The mechanism of
      how different dynamics of Hes1 expression is controlled remains to be determined.
      Here, we found that the seed sequence of microRNA-9 (miR-9) is complementary to
      the 3'-UTR sequence of Hes1 mRNA. MiR-9 is highly expressed in the ventricular
      zone of the developing brain, which contains neural stem cells, but it is not
      expressed in the roof plate or the floor plate. Over-expression of miR-9
      negatively regulates the Hes1 protein expression by interacting with the 3'-UTR
      of Hes1 mRNA, thereby inducing cell cycle exit and neuronal differentiation.
      Conversely, knockdown of miR-9 inhibits neuronal differentiation. Furthermore,
      knockdown of miR-9 inhibits the oscillatory expression of Hes1 mRNA in neural
      stem cells. These results indicate that miR-9 regulates the proliferation and
      differentiation of neural stem cells by controlling the dynamics of Hes1
      expression in the developing brain.

PMID- 23134482
TI  - Stable isotope N-phosphorylation labeling for Peptide de novo sequencing and
      protein quantification based on organic phosphorus chemistry.
AB  - In this paper, we describe the development of a novel stable isotope N
      phosphorylation labeling (SIPL) strategy for peptide de novo sequencing and
      protein quantification based on organic phosphorus chemistry. The labeling
      reaction could be performed easily and completed within 40 min in a one-pot
      reaction without additional cleanup procedures. It was found that N
      phosphorylation labeling reagents were activated in situ to form labeling
      intermediates with high reactivity targeting on N-terminus and epsilon-amino
      groups of lysine under mild reaction conditions. The introduction of N-terminal
      labeled phosphoryl group not only improved the ionization efficiency of peptides
      and increased the protein sequence coverage for peptide mass fingerprints but
      also greatly enhanced the intensities of b ions, suppressed the internal
      fragments, and reduced the complexity of the tandem mass spectrometry (MS/MS)
      fragmentation patterns of peptides. By using nano liquid chromatography chip/time
      of-flight mass spectrometry (nano LC-chip/TOF MS) for the protein quantification,
      the obtained results showed excellent correlation of the measured ratios to
      theoretical ratios with relative errors ranging from 0.5% to 6.7% and relative
      standard deviation of less than 10.6%, indicating that the developed method was
      reproducible and precise. The isotope effect was negligible because of the
      deuterium atoms were placed adjacent to the neutral phosphoryl group with high
      electrophilicity and moderately small size. Moreover, the SIPL approach used
      inexpensive reagents and was amenable to samples from various sources, including
      cell culture, biological fluids, and tissues. The method development based on
      organic phosphorus chemistry offered a new approach for quantitative proteomics
      by using novel stable isotope labeling reagents.

PMID- 23134483
TI  - Investigation into causes of abnormal cerebral MRI findings following PVAC duty
      cycled, phased RF ablation of atrial fibrillation.
AB  - INTRODUCTION: Left atrial catheter ablation of the pulmonary veins (PVs) is an
      established option for patients with atrial fibrillation (AF). Asymptomatic
      cerebral emboli (ACE) detected by diffusion weighted MRI (DW-MRI) following AF
      ablation has been reported at varying rates. This variability may be linked to
      procedural variables and demographic risk factors. Animal studies with the
      multielectrode pulmonary vein ablation catheter (PVAC) have identified potential
      sources of emboli, including air introduced during PVAC introduction, inadequate
      anticoagulation, and high current densities when the distal (E1) and proximal
      (E10) electrodes are in contact. We sought to evaluate the incidence, size, and
      number of DW-MRI findings with procedural modifications that potentially reduce
      the embolic load. METHODS: Thirty-seven AF patients (59 +/- 10 years, 73% male,
      all with paroxysmal AF, left atrial [LA] diameter 44 +/- 7 mm, left ventricular
      ejection fraction 57 +/- 7%) underwent MRI sequences preceding ablation, within
      24 hours postablation, and at 4-6 weeks. During the procedure all patients were
      on uninterrupted phenprocoumon, an attempted activated clotting time (ACT) level
      >300 seconds, had the PVAC introduced under saline, and antral ablation was
      started with a 2:1 bipolar/unipolar mode. Files from the ablation unit (GENius
      v14.4) were retrospectively analyzed to determine the relationship between E1 and
      E10 in close proximity and DW-MRI findings. RESULTS: Post procedure, 10/37
      patients (27%) were positive for new DWI cerebral lesions. Nine of 10 patients
      had a single lesion, and 1/10 patient had 2 lesions. Average lesion size was 3.1
      +/- 3.9 mm (2-14 mm). One of 10 (10%) had lesions at MRI follow-up. No
      neurological symptoms were observed. Eighteen of 37 (49%) of procedures had
      evidence of E1/E10 interaction. In the subgroup of patients with and without E1
      and E10 in close proximity, the DW-MRI rate was 8/18 (44%) and 2/19 (11%),
      respectively (P = 0.029). CONCLUSIONS: The source of positive DW-MRI findings in
      LA ablation involves several factors. Controlling anticoagulation and careful
      sheath management helps to reduce the number and size of DW-MRI lesions. With the
      PVAC catheter, an ablation with the E1 and E10 in close proximity increases the
      risk of a DW-MRI finding. In the future, electrodes E1 and E10 should be kept
      apart to help reduce the incidence of acute ACE.

PMID- 23134484
TI  - Tone of voice guides word learning in informative referential contexts.
AB  - Listeners infer which object in a visual scene a speaker refers to from the
      systematic variation of the speaker's tone of voice (ToV). We examined whether
      ToV also guides word learning. During exposure, participants heard novel
      adjectives (e.g., "daxen") spoken with a ToV representing hot, cold, strong,
      weak, big, or small while viewing picture pairs representing the meaning of the
      adjective and its antonym (e.g., elephant-ant for big-small). Eye fixations were
      recorded to monitor referent detection and learning. During test, participants
      heard the adjectives spoken with a neutral ToV, while selecting referents from
      familiar and unfamiliar picture pairs. Participants were able to learn the
      adjectives' meanings, and, even in the absence of informative ToV, generalize
      them to new referents. A second experiment addressed whether ToV provides
      sufficient information to infer the adjectival meaning or needs to operate within
      a referential context providing information about the relevant semantic
      dimension. Participants who saw printed versions of the novel words during
      exposure performed at chance during test. ToV, in conjunction with the
      referential context, thus serves as a cue to word meaning. ToV establishes
      relations between labels and referents for listeners to exploit in word learning.

PMID- 23134485
TI  - Glycaemic variability in paediatric patients with type 1 diabetes on continuous
      subcutaneous insulin infusion (CSII) or multiple daily injections (MDI): a cross
      sectional cohort study.
AB  - OBJECTIVE: This cross-sectional observational cohort study was designed to
      investigate i) whether glycaemic variability in paediatric patients with type 1
      diabetes is lower in those using an insulin pump (CSII) compared with those using
      multiple daily insulin injections (MDI) and ii) whether urinary F2 -isoprostanes
      and/or urinary prostaglandin F2 excretion as surrogate marker of oxidative stress
      and cyclooxygenase activity are associated with glycaemic variability. METHODS:
      48 paediatric patients with type 1 diabetes (22 using an insulin pump) underwent
      an ambulatory 3-day continuous glucose monitoring. All patients continued with
      normal daily activities and collected urine for two consecutive 24 h periods. The
      glucose pentagon was used to calculate the glycaemic risk parameter. RESULTS:
      Insulin requirements, HDL-cholesterol, the mean of glycaemic excursions (P <
      0.01) and the standard deviation of mean glucose concentration (P < 0.05) were
      significantly lower in patients with CSII compared with those using MDI. By
      contrast, averaged HbA1c during the last twelve months as well as at the time of
      sensor insertion did not differ significantly between both groups. Summarizing
      characteristic parameter of acute and long-term metabolic control into the
      glucose pentagon revealed a significantly lower glycaemic risk parameter in CSI
      patients compared with both, healthy subjects and patients using MDI (P < 0.05).
      CONCLUSIONS: Paediatric patients with type 1 diabetes using an insulin pump
      presented with lower glycaemic variability and a concomitantly lower glycaemic
      risk parameter compared with those using MDII. Whether these findings translate
      into a lower risk of diabetes associated cardiovascular complications remains to
      be elucidated.

PMID- 23134486
TI  - Regulation of glycogen synthase from mammalian skeletal muscle--a unifying view
      of allosteric and covalent regulation.
AB  - It is widely accepted that insufficient insulin-stimulated activation of muscle
      glycogen synthesis is one of the major components of non-insulin-dependent (type
      2) diabetes mellitus. Glycogen synthase, a key enzyme in muscle glycogen
      synthesis, is extensively regulated, both allosterically (by glucose-6-phosphate,
      ATP, and others) and covalently (by phosphorylation). Although glycogen synthase
      has been a topic of intense study for more than 50 years, its kinetic
      characterization has been confounded by its large number of phosphorylation
      states. Questions remain regarding the function of glycogen synthase regulation
      and the relative importance of allosteric and covalent modification in fulfilling
      this function. In this review, we consider both earlier kinetic studies and more
      recent site-directed mutagenesis and crystal structure studies in a detailed
      qualitative discussion of the effects of regulation on the kinetics of glycogen
      synthase. We propose that both allosteric and covalent modification of glycogen
      synthase may be described by a Monod-Wyman-Changeux model in terms of apparent
      changes to L, the equilibrium constant for transition between the T and R
      conformers. As, with the exception of L, all parameters of this model are
      independent of the glycogen synthase phosphorylation state, the need to determine
      kinetic parameters for all possible states is eliminated; only the relationship
      between a particular state and L must be established. We conclude by suggesting
      that renewed efforts to characterize the relationship between phosphorylation and
      the kinetics of glycogen synthase are essential in order to obtain a better
      quantitative understanding of the function of glycogen synthesis regulation. The
      model we propose may prove useful in this regard.

PMID- 23134487
TI  - Oxinobactin and sulfoxinobactin, abiotic siderophore analogues to enterobactin
      involving 8-hydroxyquinoline subunits: thermodynamic and structural studies.
AB  - The synthesis of two new iron chelators built on the tris-l-serine trilactone
      scaffold of enterobactin and bearing a 8-hydroxyquinoline (oxinobactin) or 8
      hydroxyquinoline-5-sulfonate (sulfoxinobactin) unit has been described. The X-ray
      structure of the ferric oxinobactin has been determined, exhibiting a slightly
      distorted octahedral environment for Fe(III) and a Delta configuration. The
      Fe(III) chelating properties have been examined by potentiometric and
      spectrophotometric titrations in methanol-water 80/20% w/w solvent for
      oxinobactin and in water for sulfoxinobactin. They reveal the extraordinarily
      complexing ability (pFe(III) values) of oxinobactin over the p[H] range 2-9, the
      pFe value at p[H] 7.4 being 32.8. This was supported by spectrophotometric
      competition showing that oxinobactin removes Fe(III) from ferric enterobactin at
      p[H] 7.4. In contrast, the Fe(III) affinity of sulfoxinobactin was largely lower
      as compared to oxinobactin but similar to that of the ligand O-TRENSOX having a
      TREN backbone. These results are discussed in relation to the predisposition by
      the trilactone scaffold of the chelating units. Some comparisons are also made
      with other quinoline-based ligands and hydroxypyridinonate ligand (hopobactin). 

PMID- 23134488
TI  - Phenylene vinylene platinum(II) acetylides with prodigious two-photon absorption.
AB  - The linear and nonlinear optical properties of a series of linear and cross
      conjugated platinum(II) acetylide complexes that contain extended p-(phenylene
      vinylene) chromophores are reported. The complexes exhibit very high femtosecond
      two-photon absorption (2PA) cross section values (sigma(2) up to 10,000 GM), as
      measured by nonlinear transmission (NLT) and two-photon excited fluorescence
      (2PEF) methods. The large 2PA cross sections span a broad range of wavelengths,
      570-810 nm, and they overlap with the triplet excited state absorption. Spectral
      coincidence of high cross section 2PA and triplet absorption is a key feature
      giving rise to efficient dual-mode optical power limiting (OPL).

PMID- 23134489
TI  - Overview and introduction: the blood-brain barrier in health and disease.
AB  - This article introduces the special issue on "Blood-Brain Barrier and Epilepsy."
      We review briefly current understanding of the structure and function of the
      blood-brain barrier (BBB), including its development and normal physiology, and
      ways in which it can be affected in pathology. The BBB formed by the endothelium
      of cerebral blood vessels is one of three main barrier sites protecting the
      central nervous system (CNS). The barrier is not a rigid structure, but a dynamic
      interface with a range of interrelated functions, resulting from extremely
      effective tight junctions, transendothelial transport systems, enzymes, and
      regulation of leukocyte permeation, which thereby generates the physical,
      transport, enzymatic, and immune regulatory functions of the BBB. The brain
      endothelial cells are important components of a "modular" structure, the
      neurovascular unit (NVU), with several associated cell types and extracellular
      matrix components. Modern methods have helped in identifying a range of proteins
      involved in barrier structure and function, and recent studies have revealed
      important stages, cell types, and signaling pathways important in BBB
      development. There is a growing list of CNS pathologies showing BBB dysfunction,
      with strong evidence that this can play a major role in certain disease
      etiologies. The articles that follow in this issue summarize in more detail
      reports and discussions of the recent international meeting on "BBB in
      Neurological Dysfunctions," which took place recently at Ben-Gurion University of
      the Negev Desert Campus (Beer-Sheva, Israel), focusing on the link between
      experimental and clinical studies, and the ways in which these lead to improved
      drug treatments.

PMID- 23134490
TI  - Blood-brain barrier dysfunction in brain diseases: clinical experience.
AB  - The blood-brain barrier, a unique feature of the cerebral vasculature, is gaining
      attention as a feature in common neurologic disorders including stroke, traumatic
      brain injury, epilepsy, and schizophrenia. Although acute blood-brain barrier
      dysfunction can induce cerebral edema, seizures, or neuropsychiatric symptoms,
      epileptogenesis and cognitive decline are among the chronic effects. The
      mechanisms underlying blood-brain barrier dysfunction are diverse and may range
      from physical endothelial damage in traumatic brain injury to degradation of
      extracellular matrix proteins via matrix metalloproteinases as part of an
      inflammatory response. Clinically, blood-brain barrier dysfunction is often
      detected using contrast-enhanced imaging. However, these techniques do not give
      any insights into the underlying mechanism. Elucidating the specific pathways of
      blood-brain barrier dysfunction at different time points and in different brain
      diseases using novel imaging techniques promises a more accurate blood-brain
      barrier terminology as well as new treatment options and personalized treatment.

PMID- 23134491
TI  - Imaging blood-brain barrier dysfunction in animal disease models.
AB  - The blood-brain barrier (BBB) is a highly complex structure, which separates the
      extracellular fluid of the central nervous system (CNS) from the blood of CNS
      vessels. A wide range of neurologic conditions, including stroke, epilepsy,
      Alzheimer's disease, and brain tumors, are associated with perturbations of the
      BBB that contribute to their pathology. The common consequence of a BBB
      dysfunction is increased permeability, leading to extravasation of plasma
      constituents and vasogenic brain edema. The BBB impairment can persist for long
      periods, being involved in secondary inflammation and neuronal dysfunction, thus
      contributing to disease pathogenesis. Therefore, reliable imaging of the BBB
      impairment is of major importance in both clinical management of brain diseases
      and in experimental research. From landmark studies by Ehrlich and Goldman, the
      use of dyes (probes) has played a critical role in understanding BBB functions.
      In recent years methodologic advances in morphologic and functional brain imaging
      have provided insight into cellular and molecular interactions underlying BBB
      dysfunction in animal disease models. These imaging techniques, which range from
      in situ staining to noninvasive in vivo imaging, have different spatial
      resolution, sensitivity, and capacity for quantitative and kinetic measures of
      the BBB impairment. Despite significant advances, the translation of these
      techniques into clinical applications remains slow. This review outlines key
      recent advances in imaging techniques that have contributed to the understanding
      of BBB dysfunction in disease and discusses major obstacles and opportunities to
      advance these techniques into the clinical realm.

PMID- 23134492
TI  - Impaired neurovascular coupling to ictal epileptic activity and spreading
      depolarization in a patient with subarachnoid hemorrhage: possible link to blood
      brain barrier dysfunction.
AB  - Spreading depolarization describes a sustained neuronal and astroglial
      depolarization with abrupt ion translocation between intraneuronal and
      extracellular space leading to a cytotoxic edema and silencing of spontaneous
      activity. Spreading depolarizations occur abundantly in acutely injured human
      brain and are assumed to facilitate neuronal death through toxic effects,
      increased metabolic demand, and inverse neurovascular coupling. Inverse coupling
      describes severe hypoperfusion in response to spreading depolarization. Ictal
      epileptic events are less frequent than spreading depolarizations in acutely
      injured human brain but may also contribute to lesion progression through
      increased metabolic demand. Whether abnormal neurovascular coupling can occur
      with ictal epileptic events is unknown. Herein we describe a patient with
      aneurysmal subarachnoid hemorrhage in whom spreading depolarizations and ictal
      epileptic events were measured using subdural opto-electrodes for direct current
      electrocorticography and regional cerebral blood flow recordings with laser
      Doppler flowmetry. Simultaneously, changes in tissue partial pressure of oxygen
      were recorded with an intraparenchymal oxygen sensor. Isolated spreading
      depolarizations and clusters of recurrent spreading depolarizations with
      persistent depression of spontaneous activity were recorded over several days
      followed by a status epilepticus. Both spreading depolarizations and ictal
      epileptic events where accompanied by hyperemic blood flow responses at one
      optode but mildly hypoemic blood flow responses at another. Of note, quantitative
      analysis of Gadolinium-diethylene-triamine-pentaacetic acid (DTPA)-enhanced
      magnetic resonance imaging detected impaired blood-brain barrier integrity in the
      region where the optode had recorded the mildly hypoemic flow responses. The data
      suggest that abnormal flow responses to spreading depolarizations and ictal
      epileptic events, respectively, may be associated with blood-brain barrier
      dysfunction.

PMID- 23134493
TI  - Blood-brain barrier, epileptogenesis, and treatment strategies in cortical
      dysplasia.
AB  - Cortical dysplasia (CD) is one of the most important causes of intractable
      epilepsy. The precise mechanisms of epileptogenesis in CD are not known. Using CD
      animal models, we attempted to understand the mechanisms and efficacy of various
      antiepileptic drugs. In two separate studies, we assessed (1) the effects of
      levetiracetam (LEV) and vagus nerve stimulation (VNS) on pentylenetetrazol (PTZ)
      kindled rats, and (2) the effects of LEV and topiramate (TPM) on rats with CD and
      hyperthermia (HT). In the HT-induced rats with CD study, LEV and TPM decreased
      both the intensity of seizures and the number of rats with seizure. In these
      studies, we used immunocytochemistry (occludin, glial fibrillary acidic protein
      [GFAP], and P-glycoprotein [Pgp antibodies] and electron microscopy (EM) (sodium
      fluorescein [NaFlu]) and horseradish peroxidase [HRP]) to assess blood-brain
      barrier (BBB) integrity. Both LEV and TPM protected BBB. In PTZ- kindled rats
      with CD, both LEV and VNS reduced the duration of seizures. Immunocytochemistry
      and EM revealed no BBB impairment in any of the treatment groups. In a second set
      of experiments, we assessed the relationship between disruption of vascular
      components and epileptogenesis. Astrocytic albumin uptake in focal epileptogenic
      lesions with vascular components suggested that dysfunction of the BBB
      contributes immediately to epileptogenesis, rather than simply resulting from
      seizure activity. Hemosiderin deposits were seen as potential epileptogenic
      triggers in vascular malformations (e.g., cavernomas [CA] or arteriovenous
      malformations [AVMs] with or without a dysplastic cortical component). However,
      we found strikingly high accumulation of astrocytic albumin deposits in
      surgically removed brain parenchyma in the vicinity of CAs and AVMs from patients
      with pharmacoresistant epilepsy, which suggests different pathophysiologic
      dispersion pathways for hemosiderin and albumin in vascular lesions.

PMID- 23134494
TI  - Blood-brain barrier dysfunction-induced inflammatory signaling in brain pathology
      and epileptogenesis.
AB  - The protection of the brain from blood-borne toxins, proteins, and cells is
      critical to the brain's normal function. Accordingly, a compromise in the blood
      brain barrier (BBB) function accompanies many neurologic disorders, and is
      tightly associated with brain inflammatory processes initiated by both
      infiltrating leukocytes from the blood, and activation of glial cells. Those
      inflammatory processes contribute to determining the severity and prognosis of
      numerous neurologic disorders, and can both cause, and result from BBB
      dysfunction. In this review we examine the role of BBB and inflammatory
      responses, in particular activation of transforming grown factor beta (TGFbeta)
      signaling, in epilepsy, stroke, and Parkinson's disease.

PMID- 23134496
TI  - Mechanisms underlying blood-brain barrier dysfunction in brain pathology and
      epileptogenesis: role of astroglia.
AB  - Astrocytes are increasingly recognized as equal partners to neurons, also
      contributing to neurologic disorders such as epilepsy. Activated astrocytes are a
      common hallmark in patients with mesial temporal lobe epilepsy and Ammon's horn
      sclerosis. Blood-brain barrier (BBB) opening during status epilepticus has short
      term proepileptic effects, as the ionic composition of serum interferes with
      neuronal excitability. In the long run, astrocytic uptake of albumin induces
      transforming growth factor beta (TGFbeta)-mediated signaling cascades, leading to
      changes in astrocytic properties. Down-regulation of astrocytic inward rectifier
      K(+)  channels and altered surface expression of the water channel, aquaporin 4
      results in disturbances in spatial K(+)  buffering, thereby rendering the tissue
      more seizure prone. The expression of astrocytic gap junctional proteins connexin
      43 (Cx43) and connexin 30 (Cx30) is altered in epilepsy, and changes in gap
      junctional communication were found in sclerotic hippocampal tissue in animal
      models of epilepsy. Although gap junctional communication might exert both
      proepileptic and antiepileptic effects, double knock out of Cx43 and Cx30
      resulted in occurrence of spontaneous epileptiform events. Seizures are
      associated with massive increases in cerebral blood flow in order to cover the
      increased energy demand. Hemodynamic responses at the microcirculation level are
      mediated by astrocyte-pericyte interactions, sharing common mechanisms with
      spatial K(+)  buffering. Although many of the astrocytic mechanisms involving
      spatial K(+)  buffering, nitric oxide, adenosine, and metabotropic glutamate
      receptor (mGluR)-mediated signalling are altered in epilepsy, little is known how
      these alterations affect neurovascular coupling. In conclusion, astrocytic
      activation preceding alterations in neuronal function might critically contribute
      to epileptogenesis. Therefore, astrocytes represent a promising new target for
      the development of antiepileptic drugs.

PMID- 23134497
TI  - P-glycoprotein imaging in temporal lobe epilepsy: in vivo PET experiments with
      the Pgp substrate [11C]-verapamil.
AB  - Overexpression of the multidrug efflux transporter P-glycoprotein (Pgp) at the
      blood-brain barrier (BBB) is thought to be involved in pharmacoresistance in
      epilepsy by extruding antiepileptic drugs (AEDs) from their target site. To
      explore this hypothesis, positron emission tomography (PET) scans were performed
      with the Pgp substrate-verapamil (VPM) in animal models before and after status
      epilepticus (SE) and in patients with temporal lobe epilepsy (TLE) and healthy
      controls. In addition to baseline scans, a second VPM-PET scan was performed
      after administration of the Pgp inhibitor tariquidar (TQD), showing that VPM
      uptake at baseline and its increase after Pgp inhibition are reduced in animals
      following SE compared to baseline, and in refractory TLE relative to healthy
      controls. In animal models, brain regions with increased Pgp expression
      (cerebellum, thalamus, and hippocampus) showed reduced influx rate constants from
      blood to brain, K(1), of the radiolabeled Pgp substrate relative to control
      animals. In human studies, preliminary findings are lower K(1) values in
      refractory compared to seizure-free patients and attenuated increase of K(1) for
      temporal lobe regions in patients with TLE compared to healthy controls. In
      summary, there is lower brain uptake of the Pgp substrate VPM in Pgp-rich areas
      of animals 2 days following SE, as well as lower increase in VPM brain uptake
      after TQD in patients with refractory TLE compared to healthy controls,
      supporting the hypothesis of increased cerebral Pgp function following prolonged
      seizures and as a mechanism contributing to drug resistance in refractory
      epilepsy. The observation of reduced VPM uptake in refractory compared to seizure
      free patients with TLE is consistent with multiple mechanisms affecting Pgp
      function, including uncontrolled seizures.

PMID- 23134495
TI  - Inflammatory events at blood-brain barrier in neuroinflammatory and
      neurodegenerative disorders: implications for clinical disease.
AB  - Proper function of the neurovasculature is required for optimal brain function
      and preventing neuroinflammation and neurodegeneration. Within this review, we
      discuss alterations of the function of the blood-brain barrier in neurologic
      disorders such as multiple sclerosis, epilepsy, and Alzheimer's disease and
      address potential underlying mechanisms.

PMID- 23134498
TI  - Why and how to target angiogenesis in focal epilepsies.
AB  - We previously reported that blood-brain barrier (BBB) disruption was associated
      with a pathologic angiogenesis in patients with intractable temporal lobe
      epilepsy (TLE) and in vivo models. This was confirmed by the overexpression of
      vascular endothelial growth factor (VEGF) in neurons and astrocytes and of its
      receptor vascular endothelial growth factor-2 (VEGF-R2) (or flk1) in endothelial
      cells. Using an original in vitro model, we showed that seizures were sufficient
      to activate the VEGF/VEGF-R2 system, which promotes vascularization and tight
      junction disassembly. Such a BBB dysfunction was shown to contribute to
      epileptogenesis. Therefore, we postulate that drugs that target the specific VEGF
      R2 pathways involved in permeability are able to repair the BBB, and, therefore,
      could reduce epileptogenicity.

PMID- 23134499
TI  - Deeper penetration into tumor tissues and enhanced in vivo antitumor activity of
      liposomal paclitaxel by pretreatment with angiogenesis inhibitor SU5416.
AB  - The recently emerged concept of "vessel normalization" implies that judicious
      blockade of vascular endothelial growth factor (VEGF) signaling may transiently
      "normalize" the tumor vasculature, making it more suitable for tumor disposition
      of subsequently administered drugs. In this study, therefore, the effect of
      pretreatment with SU5416, a selective VEGF receptor-2 inhibitor, on tumor
      disposition and in vivo antitumor activity of polyethylene glycol (PEG)-modified
      liposomal paclitaxel (PL-PTX) was evaluated in Colon-26 solid tumor-bearing mice.
      To improve the solubility and in vivo disposition characteristics of SU5416, the
      inhibitor was formulated in PEGylated O/W emulsion (PE-SU5416). Pretreatment with
      PE-SU5416 significantly enhanced the in vivo antitumor effect of PL-PTX, although
      PE-SU5416 administration alone did not show any antitumor effect. Immunostaining
      for endothelial cells and pericytes demonstrated that the pretreatment with PE
      SU5416 enhanced the pericyte coverage of the tumor vasculature. In addition,
      tumors treated with PE-SU5416 contained significantly smaller hypoxic regions
      compared with the nontreated control group, demonstrating that structural
      normalization of the tumor vasculature resulted in an improvement in tumor vessel
      functions, including oxygen supply. Furthermore, the pretreatment with PE-SU5416
      increased the distribution of PEG liposomes and included PTX in the core region
      of the tumor, as well as conversely decreasing the ratio of their peripheral
      distribution. These results suggest that the structural and functional
      normalization of the tumor vasculature by the pretreatment with PE-SU5416 enabled
      liposomes to reach the deeper regions within tumor tissues, leading to more
      potent antitumor activity of PL-PTX. 

PMID- 23134500
TI  - Extensive polymorphism and evidence of selection pressure on major
      histocompatibility complex DLA-DRB1, DQA1 and DQB1 class II genes in Croatian
      grey wolves.
AB  - The genes of the major histocompatibility complex (MHC) are a key component of
      the mammalian immune system and have become important molecular markers for
      measuring fitness-related genetic variation in wildlife populations. Because of
      human persecution and habitat fragmentation, the grey wolf has become extinct
      from a large part of Western and Central Europe, and remaining populations have
      become isolated. In Croatia, the grey wolf population, part of the Dinaric-Balkan
      population, shrank nearly to extinction during the 20th century, and is now
      legally protected. Using the cloning-sequencing method, we investigated the
      genetic diversity and evolutionary history of exon 2 of MHC class II DLA-DRB1,
      DQA1 and DQB1 genes in 77 individuals. We identified 13 DRB1, 7 DQA1 and 11 DQB1
      highly divergent alleles, and 13 DLA-DRB1/DQA1/DQB1 haplotypes. Selection
      analysis comparing the relative rates of non-synonymous to synonymous mutations
      (d(N)/d(S)) showed evidence of positive selection pressure acting on all three
      loci. Trans-species polymorphism was found, suggesting the existence of balancing
      selection. Evolutionary codon models detected considerable difference between
      alpha and beta chain gene selection patterns: DRB1 and DQB1 appeared to be under
      stronger selection pressure, while DQA1 showed signs of moderate selection. Our
      results suggest that, despite the recent contraction of the Croatian wolf
      population, genetic variability in selectively maintained immune genes has been
      preserved.

PMID- 23134502
TI  - An unusual case of ocular melanosis and limbal melanocytoma with benign
      intraorbital extension in a dog.
AB  - This case report describes concurrent ocular melanosis and limbal melanocytoma in
      a 6-year-old Golden Retriever dog. Three years prior, the pet was examined for
      progressive corneal pigmentation and started on topical Tacrolimus but was
      subsequently lost to followup. Current ophthalmic examination revealed a large
      pigmented limbal mass and severe corneal pigmentation of the left eye as well as
      a small focal raised pigmented mass of the right third eyelid. Due to extent and
      rapidity of tumor growth, the left eye was removed via transconjunctival
      enucleation and submitted for histopathologic examination. At the time of
      surgery, numerous orbital structures including intraorbital fat, extraocular
      muscles, and portions of the proximal nasolacrimal drainage apparatus contained
      multifocal areas of black pigmentation. These tissues were subsequently removed
      and submitted for microscopic analysis. The pigmented mass of the right third
      eyelid was also excised. Histopathology of the left eye and orbital contents
      revealed a limbal melanocytoma extending to the bulbar conjunctiva and orbital
      space forming a large, markedly necrotic mass. Diffuse, severe ocular melanosis,
      abnormal stromal pigmentation of the sclera and orbital tissues, and corneal
      stromal pigmentation were noted. The mass of the right third eyelid was confirmed
      to be a conjunctival melanocytoma. To the authors' knowledge, this is the first
      report of concurrent ocular melanosis and limbal melanocytoma with orbital
      infiltration. The peculiar multifocal distribution of melanocytes throughout
      ocular connective tissues may explain the development of multiple melanocytic
      lesions in this patient. 

PMID- 23134503
TI  - Amyotrophic lateral sclerosis in Piedmont (Italy): a Bayesian spatial analysis of
      the incident cases.
AB  - In the analysis of risk factors in amyotrophic lateral sclerosis (ALS), few
      ecological studies, based on the relationship between the distribution of the
      patients in a given area and the environmental exposures, have been performed.
      The aim of our study was to depict the spatial risk distribution of ALS in
      Piedmont's resident population during the period 1995-2004. Data were collected
      from the Piedmont and Aosta Valley Register for ALS, which is a prospective
      epidemiological archive for gathering all the ALS incident cases in north-western
      Italy. Only cases from Piedmont were considered. The Besag, York and Mollie model
      was used to estimate smoothed standardized incidence ratios (SIR) by
      municipalities either overall or stratified by gender and age class. Results
      demonstrated that excess of risk was particularly evident in the area of Cuneo,
      Alessandria and Vercelli (SIR > 1.2). The results were evident for both genders,
      but in particular for males aged 35-60 years. Given the geographic distribution
      of rural areas, our results suggest that the environmental exposure to
      agricultural chemicals could be possibly linked to this pattern. Despite some
      limits of the spatial analysis in the study of rare diseases, results appear
      coherent with literature data, stimulating other in-depth analysis in this field
      of research.

PMID- 23134504
TI  - Report on the ALS Association's drug discovery workshop.

PMID- 23134505
TI  - Premorbid body mass index and risk of amyotrophic lateral sclerosis.
AB  - Our objective was to determine if amyotrophic lateral sclerosis (ALS) risk varies
      according to body mass index (BMI) captured up to three decades earlier. At
      baseline 537,968 females and 562,942 males in five ongoing cohorts reported
      height, current weight and weight at age 18/21 years. During 14-28 years of
      follow-up, 1153 participants developed ALS. Cohort-specific Cox proportional
      hazards models were used to estimate rates that were then pooled with random
      effects models. Results showed that lower BMI at baseline was associated with
      ALS; for each 5-unit increase in BMI, ALS rates were 21% lower (95% CI 14% 27%).
      Compared to individuals with healthy BMI, ALS rates were significantly lower
      among the overweight (RR = 0.76 (95% CI 0.62-0.93)) and obese (RR = 0.73 (95% CI
      0.55-0.96)). Among never smokers the association persisted: RR = 0.75 (95% CI
      0.65-0.85) for each 5-unit increase. Excluding the first seven years of follow
      up, the associations were materially unchanged suggesting that weight loss from
      undiagnosed disease does not fully explain the findings. Overall, 75% of males
      and females had a healthy BMI at age 18/21 years, 15% of males and 8% of females
      were overweight or obese; there was no association with ALS although numbers with
      an unhealthy weight were small. In conclusion, these findings support an
      association between lower premorbid BMI and ALS.

PMID- 23134506
TI  - pNfH is a promising biomarker for ALS.
AB  - A diagnostic biomarker for ALS would permit early intervention with disease
      modifying therapies while a biomarker for disease activity could accelerate the
      pace of drug discovery by facilitating shorter, and less costly, drug trials to
      be conducted with a smaller number of patients. Neurofilaments are the most
      abundant neuronal cytoskeletal protein. We set out to determine whether pNfH was
      a credible biomarker for ALS. pNfH levels were determined using an ELISA for 150
      ALS subjects and 140 controls. We demonstrated a seven-fold elevation in the
      cerebrospinal fluid (CSF) levels of phosphorylated neurofilament heavy subunit
      (pNfH) in ALS (median = 2787 pg/ml, n = 150), compared to headache and other
      benign controls (394 pg/ml, n = 100, p = < 0.05). There was a 10-fold elevation
      of pNfH compared to ALS mimics (266 pg/ml, n = 20) and other neurodegenerative
      and inflammatory conditions (279 pg/ml for n = 20) which was also highly
      significant (p = < 0.05). pNfH achieved a diagnostic sensitivity of 90% and
      specificity of 87% in distinguishing ALS from all controls. We also detected an
      inverse correlation between CSF pNfH levels and disease duration (time from
      symptom onset to death, r(2 = )0.1247, p = 0.001). In conclusion, pNfH represents
      a promising candidate for inclusion in a panel of diagnostic and prognostic
      biomarkers.

PMID- 23134507
TI  - Validation of robust tools to measure sialorrhea in amyotrophic lateral
      sclerosis: a study in a large French cohort.
AB  - There is an unmet need for validated tools to measure sialorrhea in amyotrophic
      lateral sclerosis, especially to evaluate treatments. We assessed the inter
      /intra-rate reviewer reliability of two scales: the Oral Secretion Scale (OSS),
      specifically developed for ALS patients, and the Sialorrhea Scoring Scale (SSS),
      initially developed for Parkinson's disease patients. Sialorrhea was rated in 69
      ALS consecutive patients by four evaluators: two neurologists, one nurse and one
      speech therapist. Inter-rater reliability was evaluated by the light kappa
      coefficient and intra-rater reliability by the weighted kappa coefficient. We
      also compared patients' and caregivers' answers. Results demonstrated that the
      two scales present a high inter-/intra-rater reliability: weighted kappas were
      0.85 for both scales and light kappas 0.89 for the OSS and 0.88 for the SSS. Both
      scales also showed a good intra-profession reliability (OSS kappa = 0.84; SSS
      kappa = 0.79) and agreement between patients' and caregivers' answers. The SSS
      showed a higher responsiveness compared to OSS. In conclusion, both Oral
      Secretion Scale and Sialorrhea Scoring Scale are reliable tools to measure
      sialorrhea in ALS patients. Because of the wide range of salivation degrees, SSS
      may be more sensitive as a tool to evaluate treatments in patients with severe
      hypersialorrhea.

PMID- 23134508
TI  - Statins and amyotrophic lateral sclerosis: a systematic review and meta-analysis.
AB  - OBJECTIVE: To evaluate the association between statins and the incidence and
      progression of amyotrophic lateral sclerosis (ALS). METHODS: Several electronic
      databases (PubMed, Embase, and EBSCO) and Chinese databases (CBM, Wanfang, and
      VIP) were searched for original articles on April 1(st), 2012. Case-control and
      cohort studies that provide information on the association between statins and
      ALS were considered eligible for inclusion. A systematic review was conducted to
      evaluate the association of statins and the incidence and progression of ALS.
      RESULTS: Two case-control studies and one cohort study that relate the risk of
      ALS to statins satisfied the inclusion criteria for the meta-analysis. The pooled
      rate ratio of statin use was 0.89 [95% CI, 0.55 to 1.42] for ALS patients versus
      non-ALS patients. Three cohort studies on the association between statins and the
      progression of ALS were identified; these suggested that no strong evidence for
      the statin-ALS progression relationship exists. No cohort studies favor the use
      of statins on ALS patients. CONCLUSIONS: No definite association between statin
      use and ALS incidence and progression has been found. Existing results are
      currently inconclusive to make scientifically supported conclusions. Further
      prospective cohort studies are still needed.

PMID- 23134509
TI  - The CMAP scan as a tool to monitor disease progression in ALS and PMA.
AB  - Amyotrophic lateral sclerosis (ALS) and progressive muscular atrophy (PMA) are
      characterized by a loss of motor units (MUs), reinnervation and, eventually,
      muscle fibre loss. These three aspects are all reflected in the compound muscle
      action potential scan (CMAP scan, a high-detail stimulus response curve), which
      visualizes large MU potentials as 'steps'. We explored changes in the CMAP scan
      over time, combined the information on steps and CMAP amplitude into a CMAP scan
      based progression score (CSPS), and correlated this score with motor unit number
      estimates (MUNE). Ten patients (three PMA, seven ALS; age 37-77 years) were
      included. CMAP scan and MUNE measurements were performed five times during a
      three-month period. Nine patients had additional measurements. The follow-up
      period was 3-24 months. Results demonstrated that abnormalities in steps preceded
      a decline in maximum CMAP amplitude during follow-up. Usually, both steps and
      maximum CMAP amplitude changed between recordings. The correlation between the
      CSPS and MUNE was -0.80 (p < 0.01). In conclusion, the CMAP scan can be used to
      visualize and quantify disease progression in a muscle affected by MND. The CSPS
      is a measure of MU loss that is quick and easy to obtain and that, in contrast to
      MUNE, has no sample bias.

PMID- 23134510
TI  - Identification of RNA bound to the TDP-43 ribonucleoprotein complex in the adult
      mouse brain.
AB  - Cytoplasmic inclusions containing TDP-43 are a pathological hallmark of several
      neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and
      frontotemporal dementia. TDP-43 is an RNA binding protein involved in gene
      regulation through control of RNA transcription, splicing and transport. However,
      the function of TDP-43 in the nervous system is largely unknown and its role in
      the pathogenesis of ALS is unclear. The aim of this study was to identify genes
      in the central nervous system that are regulated by TDP-43. RNA
      immunoprecipitation with anti-TDP-43 antibody, followed by microarray analysis
      (RIP-chip), was used to isolate and identify RNA bound to TDP-43 protein from
      mouse brain. This analysis produced a list of 1839 potential TDP-43 gene targets,
      many of which overlap with previous studies and whose functions include RNA
      processing and synaptic function. Immunohistochemistry demonstrated that the TDP
      43 protein could be found at the presynaptic membrane of axon terminals in the
      neuromuscular junction in mice. In conclusion, the finding that TDP-43 binds to
      RNA that codes for genes related to synaptic function, together with the
      localization of TDP-43 protein at axon terminals, suggests a role for TDP-43 in
      the transport of synaptic mRNAs into distal processes.

PMID- 23134511
TI  - Mitochondrial genome aberrations in skeletal muscle of patients with motor neuron
      disease.
AB  - Our objective was to assess the role of defects of mitochondrial function as
      contributing factors in the pathogenesis and/or progression of amyotrophic
      lateral sclerosis (ALS); mitochondrial genome structural alterations were
      investigated. DNA lesions, point alterations and gross rearrangements were
      screened by specific applications of real-time PCR including an optimized rapid
      gene-specific method for the accurate quantification of mitochondrial DNA (mtDNA)
      lesions as well as sequencing on skeletal muscle biopsies of three patients
      presenting with motor neuron disease. We found a higher frequency of mtDNA
      lesions, including multiple deletions, particularly in the only SOD1 mutated
      patient as well as in a patient negative for mutations in SOD1 but presenting a
      severe form of the disease. The occurrence and the extent of mtDNA lesions of the
      cases here presented were consistent in all the examined clinical phenotypes of
      ALS (SOD1 related ALS, bulbar onset, spinal onset) and correlated with the
      severity of clinical course of the illness and with the presence of SOD1 mutation
      as well. In conclusion, the strong association with mtDNA damages supports the
      hypothesis that mitochondrial dysfunction in skeletal muscle may contribute to
      the pathogenesis and progression of ALS.

PMID- 23134512
TI  - Increased expression of toll-like receptor 4 and inflammatory cytokines,
      interleukin-6 in particular, in islets from a mouse model of obesity and type 2
      diabetes.
AB  - Toll-like receptor 4 (TLR4) has received much attention in the recent years due
      to its role in development of insulin resistance in type 2 diabetes mellitus. Its
      expression is elevated in fat and muscle from insulin-resistant mice. Several
      cells of the pancreatic islets, including beta-cells and resident macrophages,
      express TLR4. Our hypothesis is that expression of TLR4 and downstream signalling
      molecules in islets increases during progression of type 2 diabetes, thereby
      contributing to beta-cell damage. We investigated the hypothesis in the db/db
      mouse. Islets from male db/db (4, 8 and 15 weeks old) and control db/+ (4 and 15
      weeks old) mice were examined for mRNA expression of TLR4 and selected cytokines
      using qPCR. In addition, cytokine secretion from islets was quantified. TLR4 is
      expressed in islets from lean and obese mice, displaying a 7.4-fold higher level
      in 15 weeks old db/db relative to age-matched control (p < 0.01). During
      progression of clinical type 2 diabetes manifested by hyperglycaemia, TLR4
      expression increases 5.6-fold in islets from 15 weeks compared with 4 weeks old
      db/db mice (p < 0.01). Furthermore, both protein and mRNA levels of all cytokines
      examined increased. In particular, expression of IL-6 increased with 37 fold.
      Expression of TLR4 in db/db mouse islets increased in parallel with
      hyperglycaemia. A similar increase in expression and secretion of TNFalpha, IL-1
      and IL-6 was observed. Our results demonstrate that, in addition to its
      contribution to insulin resistance, TLR4 might also play a role in beta-cell
      dysfunction in type 2 diabetes.

PMID- 23134513
TI  - Malaria antibody persistence correlates with duration of exposure.
AB  - BACKGROUND AND OBJECTIVES: In Australia, the risk of transfusion-transmitted
      malaria is managed through the identification of 'at-risk' donors, antibody
      screening enzyme-linked immunoassay (EIA) and, if reactive, exclusion from fresh
      blood component manufacture. Donor management depends on the duration of exposure
      in malarious regions (>6 months: 'Resident', <6 months: 'Visitor') or a history
      of malaria diagnosis. We analysed antibody testing and demographic data to
      investigate antibody persistence dynamics. To assess the yield from retesting 3
      years after an initial EIA reactive result, we estimated the proportion of donors
      who would become non-reactive over this period. MATERIALS AND METHODS: Test
      results and demographic data from donors who were malaria EIA reactive were
      analysed. Time since possible exposure was estimated and antibody survival
      modelled. RESULTS: Among seroreverters, the time since last possible exposure was
      significantly shorter in 'Visitors' than in 'Residents'. The antibody survival
      modelling predicted 20% of previously EIA reactive 'Visitors', but only 2% of
      'Residents' would become non-reactive within 3 years of their first reactive EIA.
      CONCLUSION: Antibody persistence in donors correlates with exposure category,
      with semi-immune 'Residents' maintaining detectable antibodies significantly
      longer than non-immune 'Visitors'.

PMID- 23134514
TI  - Factors that influence radioactive iodine use for thyroid cancer.
AB  - BACKGROUND: There is variation in the use of radioactive iodine (RAI) as
      treatment for well-differentiated thyroid cancer. The factors involved in
      physician decision-making for RAI remain unknown. METHODS: We surveyed physicians
      involved in postsurgical management of patients with thyroid cancer from 251
      hospitals. Respondents were asked to rate the factors important in influencing
      whether a thyroid cancer patient receives RAI. Multivariable analyses controlling
      for physician age, gender, specialty, case volume, and whether they personally
      administer RAI, were performed to determine correlates of importance placed on
      patients' and physicians' worry about death from cancer and differences between
      low- versus higher-case-volume physicians. RESULTS: The survey response rate was
      63% (534/853). Extent of disease, adequacy of surgical resection, patients'
      willingness to receive RAI, and patients' age were the factors physicians were
      most likely to report as quite or very important in influencing recommendations
      for RAI to patients with thyroid cancer. Interestingly, both physicians' and
      patients' worry about death from thyroid cancer were also important in
      determining RAI use. Physicians with less thyroid cancer cases per year were more
      likely than higher-volume physicians to report patients' (p<0.001) and
      physicians' worry about death (p=0.016) as quite or very important in decision
      making. Other factors more likely to be of greater importance in determining RAI
      use for physicians with lower thyroid cancer patient volume versus higher include
      the accepted standard at the affiliated hospital (p=0.020), beliefs about RAI
      expressed by colleagues comanaging patients (p=0.003), and patient distance from
      the nearest facility administering RAI (p=0.012). CONCLUSION: In addition to the
      extent of disease and adequacy of surgical resection, physicians place importance
      on physician and patient worry about death from thyroid cancer when deciding
      whether to treat a patient with RAI. The factors important to physician decision
      making differ based on physician thyroid-cancer case-volume, with worry about
      death being more influential for low-case-volume physicians. As the mortality
      from thyroid cancer is low, the importance placed on death in decision making may
      be unwarranted.

PMID- 23134515
TI  - Histopathological characteristics of myocarditis in acute-phase Kawasaki disease.
AB  - AIMS: To elucidate the histopathological characteristics of myocarditis in acute
      phase Kawasaki disease (KD). METHODS AND RESULTS: The examined materials were
      from 29 autopsied KD patients who died within 40 disease days following onset.
      Each heart was divided into three levels: base, middle and apex. At each of these
      levels, the myocardium was divided further into the epicardial, middle and
      endocardial layers, and the time-courses of the changes in the myocarditis and
      the distribution of inflammation were analysed. Inflammatory cell infiltration,
      consisting mainly of lobulated leucocytes and large mononuclear cells, was seen
      in the myocardial interstitium in all cases. Inflammatory cell infiltration was
      already seen by disease day 6 in a patient with no coronary arteritis; it became
      prominent after day 10 and gradually disappeared after day 20. Myocarditis was
      initially distributed diffusely throughout the heart, but after day 10 it was
      localized in the base and epicardial layer. CONCLUSIONS: In KD, myocarditis
      develops even earlier than epicardial coronary arteritis; it peaks by disease day
      10 and then disappears gradually after day 20. The myocarditis is distributed
      unevenly, ranging from the entire heart to the epicardial layer of the base of
      the heart.

PMID- 23134516
TI  - GABA(B)  receptor-mediated presynaptic inhibition reverses inter-columnar
      covariability of synaptic actions by intracortical axons in the rat barrel
      cortex.
AB  - Intracortical axons originating from pyramidal cells in layer 3 of the rat
      somatosensory cortex are shared between adjacent columns, and receive the
      presynaptic inhibition that is mediated by the GABA(B)  receptor. Synaptic
      actions by intracortical axons of single layer 3 pyramidal cells covary between
      the two adjacent columns in response to stimulation of layer 3 of either column.
      We examined whether GABA(B)  receptor-mediated presynaptic inhibition affects the
      covariability of synaptic actions by intracortical axons between adjacent columns
      in slice preparations of the rat barrel cortex. Paired stimulations of
      superficial layer 3 evoked first and second excitatory postsynaptic currents
      (EPSCs) of varying amplitudes, yielding varying paired-pulse depression of EPSCs
      in layer 3 pyramidal cells that were located in the stimulated column, but not in
      its adjacent column. The amplitude of the second EPSC was inversely proportional
      to that of the first EPSC in layer 3 pyramidal cells in the stimulated column,
      yielding a negative correlation coefficient between the first and second EPSCs.
      Baclofen and CGP55845 attenuated paired-pulse depression and abolished the
      inverse relationship. Simultaneous recordings from two layer 3 pyramidal cells in
      the stimulated and adjacent columns revealed a positive correlation between the
      paired first EPSC amplitudes and a negative correlation between the paired second
      EPSC amplitudes, which, respectively, indicate the positive and negative
      covariability of synaptic actions by intracortical axons between the two adjacent
      columns. These results suggest that GABA(B)  receptor-mediated presynaptic
      inhibition can reverse the positive covariability of inter-columnar synaptic
      actions, which may serve as a basis for inter-columnar desynchronisation.

PMID- 23134517
TI  - Time-dependent density functional theory assessment of UV absorption of benzoic
      acid derivatives.
AB  - Benzoic acid (BA) derivatives of environmental relevance exhibit various
      photophysical and photochemical characteristics. Here, time-dependent density
      functional theory (TDDFT) is used to calculate photoexcitations of eight selected
      BAs and the results are compared with UV spectra determined experimentally. High
      level gas-phase EOM-CCSD calculations and experimental aqueous-phase spectra were
      used as the references for the gas-phase and aqueous-phase TDDFT results,
      respectively. A cluster-continuum model was used in the aqueous-phase
      calculations. Among the 15 exchange-correlation (XC) functionals assessed, five
      functionals, including the meta-GGA hybrid M06-2X, double hybrid B2PLYPD, and
      range-separated functionals CAM-B3LYP, omegaB97XD, and LC-omegaPBE, were found to
      be in excellent agreement with the EOM-CCSD gas-phase calculations. These
      functionals furnished excitation energies consistent with the pH dependence of
      the experimental spectra with a standard deviation (STDEV) of ~0.20 eV. A
      molecular orbital analysis revealed a pisigma* feature of the low-lying
      transitions of the BAs. The CAM-B3LYP functional showed the best overall
      performance and therefore shows promise for TDDFT calculations of processes
      involving photoexcitations of benzoic acid derivatives.

PMID- 23134518
TI  - Horizontal gene transfer from genus agrobacterium to the plant linaria in nature.
AB  - Genes can be transferred horizontally between prokaryotes and eukaryotes in
      nature. The best-studied examples occur between Agrobacterium rhizogenes and
      certain Nicotiana spp. To investigate possible additional cases of horizontal
      gene transfer in nature between Agrobacterium and plants, a real-time polymerase
      chain reaction-based approach was employed to screen 127 plant species, belonging
      to 38 families of Dicotyledones, for the presence of oncogenes homologous to the
      transfer DNA fragments (T-DNA) from both A. tumefaciens and A. rhizogenes. Among
      all of the analyzed plant species, we found that only Linaria vulgaris contained
      sequences homologous to the T-DNA of A. rhizogenes. All screened L. vulgaris
      plants from various parts of Russia contained the same homologous sequences,
      including rolB, rolC, ORF13, ORF14, and mis genes. The same opine gene is found
      in the species of Nicotiana which contain genes of A. rhizogenes. In L. vulgaris,
      there are two copies of T-DNA organized as a single tandem imperfect direct
      repeat. The plant DNA sequence of the site of integration shows similarity to a
      retrotransposon. This site is most likely silent, suggesting that the T-DNA is
      not expressed. Attempts to demonstrate expression of the T-DNA genes were
      negative. Our study indicates that the frequency of gene transfer and fixation in
      the germline from Agrobacterium to plant hosts is rare in the natural
      environment.

PMID- 23134519
TI  - Tobacco etch virus infectivity in Capsicum spp. is determined by a maximum of
      three amino acids in the viral virulence determinant VPg.
AB  - Potyvirus resistance in Capsicum spp. has been attributed to amino acid
      substitutions at the pvr1 locus that cause conformational shifts in eukaryotic
      translation initiation factor eIF4E. The viral genome-linked protein (VPg)
      sequence was isolated and compared from three Tobacco etch virus (TEV) strains,
      highly aphid-transmissible (HAT), Mex21, and N, which differentially infect
      Capsicum genotypes encoding Pvr1(+), pvr1, and pvr1(2). Viral chimeras were
      synthesized using the TEV-HAT genome, replacing HAT VPg with Mex21 or N VPg. TEV
      HAT did not infect pepper plants homozygous for either the pvr1 or pvr1(2)
      allele. However, the novel chimeric TEV strains, TEVHAT(Mex21-VPg) and TEV-HAT(N
      VPg), infected pvr1 and pvr1(2) pepper plants, respectively, demonstrating that
      VPg is the virulence determinant in this pathosystem. Three dimensional
      structural models predicted interaction between VPg and the susceptible eIF4E
      genotype in every case, while resistant genotypes were never predicted to
      interact. To determine whether there is a correlation between physical
      interaction of VPg with eIF4E and infectivity, the effects of amino acid
      variation within VPg were assessed. Interaction between pvr1(2) eIF4E and N VPg
      was detected in planta, implying that the six amino acid differences in N VPg
      relative to HAT VPg are responsible for restoring the physical interaction and
      infectivity.

PMID- 23134520
TI  - Metabolite profiling of Arabidopsis inoculated with Alternaria brassicicola
      reveals that ascorbate reduces disease severity.
AB  - The interaction between the pathogenic ascomycete Alternaria brassicicola and
      Arabidopsis was investigated by metabolite profiling. The effect of A.
      brassicicola challenge on metabolite levels was substantial, with nearly 50% of
      detected compounds undergoing significant changes. Mutations blocking ethylene,
      jasmonic acid, or ethylene signaling had little effect on metabolite levels. The
      effects of altering levels of some metabolites were tested by exogenous
      application during A. brassicicola inoculation. Gamma amino-butyric acid (GABA)
      or xylitol promoted, while trehalose and ascorbate inhibited, disease severity.
      GABA promoted, and ascorbate strongly inhibited, fungal growth in culture.
      Arabidopsis vtc1 and vtc2 mutants, that have low levels of ascorbate, were more
      susceptible to A. brassicicola. Ascorbate levels declined following A.
      brassicicola inoculation while levels of dehydroascorbate increased, resulting in
      a shift of the redox balance between these compounds in the direction of
      oxidation. These results demonstrate that ascorbate is an important component of
      resistance to this pathogen.

PMID- 23134522
TI  - Improved blood pressure control with nifedipine GITS/valsartan combination versus
      high-dose valsartan monotherapy in mild-to-moderate hypertensive patients from
      Asia: results from the ADVISE study, a randomized trial.
AB  - AIMS: ADVISE was a 12-week, multicenter, randomized, prospective, open-label,
      parallel-group study comparing combination therapy of nifedipine GITS 30 mg plus
      valsartan 80 mg (N + V) with high-dose valsartan (160 mg) monotherapy (V160) in
      Asian patients with hypertension. METHODS: Patients with hypertension
      inadequately controlled with valsartan 80 mg for at least 4 weeks were
      randomized. The coprimary endpoints were the mean changes in clinic systolic and
      diastolic blood pressures (SBP and DBP, respectively) at Week 12. Other endpoints
      included blood pressure (BP) control rate, response rate, and adverse events.
      RESULTS: The full analysis set (FAS) comprised 359 patients. Least squares (LS)
      mean changes in SBP were -18.3 mmHg (N + V; n = 177) and -16.5 mmHg (V160; n =
      182) (difference: -1.9 mmHg; P = 0.0998). DBP LS mean changes were -9.8 mmHg (N +
      V) and -7.4 mmHg (V160) (difference: -2.4 mmHg; P = 0.0011). BP control rates
      were significantly higher in the N + V group (Week 4: 51.2% vs. 38.4%, P =
      0.0138; Week 8: 68.3% vs. 50.3%, P = 0.0004; and Week 12: 71.2% vs. 55.5%, P =
      0.0024). Similar findings were observed when patients were stratified according
      to smoking status, SBP baseline quartiles, and ESC/ESH guideline-defined added
      risk category. The BP response rate was also higher in the N + V group compared
      with the V160 group. Rates of adverse drug reactions (all mild-to-moderate) were
      similar: 4.5% (N + V) and 4.4% (V160). CONCLUSIONS: Although one of the coprimary
      endpoints did not reach statistical significance, combination treatment with N +
      V provided a greater early and more consistent BP-lowering effect than
      monotherapy with V160, including superior reduction in DBP and BP control rates.

PMID- 23134523
TI  - Relationship between DNA replication and the nuclear matrix.
AB  - There is an extensive list of primary published work related to the nuclear
      matrix (NM). Here we review the aspects that are required to understand its
      relationship with DNA replication, while highlighting some of the difficulties in
      studying such a structure, and possible differences that arise from the choice of
      model system. We consider NM attachment regions of DNA and discuss their
      characteristics and potential function before reviewing data that deal
      specifically with functional interaction with DNA replication factors. Data have
      long existed indicating that newly synthesized DNA is associated with a nuclease
      resistant NM, allowing the conclusion that the elongation step of DNA synthesis
      is immobilized within the nucleus. We review in more detail the emerging data
      that suggest that prereplication complex proteins and origins of replication are
      transiently recruited to the NM during late G1 and early S-phase. Collectively,
      these data suggest that the initiation step of the DNA replication process is
      also immobilized by attachment to the NM. We outline models that discuss the
      possible spatial relationships and highlight the emerging evidence that suggests
      there may be important differences between cell types.

PMID- 23134524
TI  - Detection of the ampulla of Vater in small bowel capsule endoscopy: experience
      with two different systems.
AB  - OBJECTIVE: The aim of this study was to determine the detection rate of the
      ampulla of Vater (AoV) during small bowel capsule endoscopy (SBCE) examinations
      and compare the two SBCE systems used in our center. METHODS: SBCE procedures
      performed in our center from March 2005 to June 2011 were reviewed
      retrospectively. A single reviewer, following a detailed protocol, analyzed 30
      min of each recording to identify the AoV. RESULTS: A total of 619 SBCE
      procedures were enrolled in the study, including 262 with a PillCam SB1, 148 with
      a PillCam SB2 and 209 with a MiroCam. AoV was identified in 59 SBCE examinations
      (9.5%), consisting of 28 with a PillCam SB1 (28/262, 10.7%), 13 with a PillCam
      SB2 (13/148, 8.8%) and 18 with a MiroCam (18/209, 8.6%) (P = 0.665). The AoV was
      visualized in 53.2 frames (median 12 frames, range 1-1056 frames); and the
      detection rate was low regardless of indication, patients' characteristics, SBCE
      system used or capsule transit parameters. Bile spout was associated with a
      higher AoV detection (P = 0.003). CONCLUSIONS: The persistently low AoV detection
      rate using two different SBCE systems underlines the weakness of non-steerable
      capsule endoscopy. Furthermore, if AoV detection is taken as a surrogate marker
      of small polyp detection, it becomes obvious both that non-steerable SBCE cannot
      replace a side-viewing endoscope in the evaluation of periampullary polyps in
      familial adenomatous polyposis and that it is an infallible method in other small
      bowel polyposis states.

PMID- 23134525
TI  - Trauma-induced coagulopathy: standard coagulation tests, biomarkers of
      coagulopathy, and endothelial damage in patients with traumatic brain injury.
AB  - It remains to be debated whether traumatic brain injury (TBI) induces a different
      coagulopathy than does non-TBI. This study investigated traditional coagulation
      tests, biomarkers of coagulopathy, and endothelial damage in trauma patients with
      and without TBI. Blood from 80 adult trauma patients was sampled (median of 68
      min [IQR 48-88] post-injury) upon admission to our trauma center. Plasma/serum
      were retrospectively analyzed for biomarkers reflecting sympathoadrenal
      activation (adrenaline, noradrenaline), coagulation activation/inhibition and
      fibrinolysis (protein C, activated protein C, tissue factor pathway inhibitor,
      antithrombin, prothrombin fragment 1+2, thrombin/antithrombin complex, von
      Willebrand factor, factor XIII, d-dimer, tissue-type plasminogen activator,
      plasminogen activator inhibitor-1), immunology (interleukin [IL]6), endothelial
      cell/glycocalyx damage (soluble thrombomodulin, syndecan-1), and vasculogenesis
      (angiopoietin-1, -2). Patients were stratified according to: (1) isolated severe
      head/neck injuries (Abbreviated injury score [AIS]-head/neck >= 3, AIS-other<3)
      (isoTBI); (2) severe head/neck and extracranial injuries (AIS-head/neck >= 3, AIS
      other>3) (sTBI+other); and (3) injuries without significant head/neck injuries
      (AIS-head/neck<3, including all AIS-other scores) (non-TBI). Twenty-three
      patients presented with isoTBI, 15 with sTBI+other and 42 with non-TBI. Acute
      coagulopathy of trauma shock, defined as activated partial thromboplastin time
      (APTT) and/or international normalized ratio (INR)>35 sec and>1.2, was found in
      13%, 47%, and 5%, respectively (p=0.000). sTBI+other had significantly higher
      plasma levels of adrenaline, noradrenaline, annexin V, d-dimer, IL-6, syndecan-1,
      soluble thrombomodulin, and reduced protein C and factor XIII levels (all
      p<0.05). No significant biomarker differences were found between isoTBI and non
      TBI patients. Injury severity scale (ISS) rather than the presence or absence of
      head/neck injuries determined the hemostatic and biomarker response to the
      injury. The coagulopathy identified thus reflected the severity of injury rather
      than its localization.

PMID- 23134526
TI  - Factors determining high-sensitivity C-reactive protein values in the Spanish
      population. Di@bet.es study.
AB  - BACKGROUND: Although high-sensitivity C-reactive protein (hs-CRP) is currently
      used as a risk marker of cardiovascular disease, it has been suggested that
      genetic, clinical, biochemical or environmental factors could modify hs-CRP
      levels. The aim of this study was to investigate sources of interindividual hs
      CRP variability in the Spanish population. MATERIALS AND METHODS: A
      representative sample of the Spanish population within the di@bet.es study was
      used. Study variables included a clinical and demographic structured survey, a
      lifestyle survey, a physical examination, plasmatic hs-CRP and other biochemical
      parameters. RESULTS: Median and interquartile range of plasma hs-CRP values were
      1.73 +/- 2.75 mg/dL. Thirty per cent of the study population had hs-CRP levels
      above 3 mg/dL and 38% from 1 to 3 mg/dL. Body mass index was the strongest factor
      associated with moderate and high hs-CRP levels. Age, sex, waist-to-hip ratio,
      weight increase, plasma lipid levels, glucose metabolism (HOMA-IR and abnormal
      glucose regulation categories), pharmacological treatment (lipid-lowering agents,
      psychotropic drugs and levothyroxine), smoking, physical activity, different
      dietary patterns, quality of life and educational level were all significantly
      associated with hs-CRP levels. Interactions were observed between variables.
      These interactions modulated the effect of previously described factors on hs
      CRP. CONCLUSIONS: Thirty per cent of the Spanish population have hs-CRP levels
      considered to represent a cardiovascular risk. Different clinical,
      anthropometric, biochemical and environmental variables modulate hs-CRP levels.
      In addition, multiple interactions between variables complicate the
      interpretation of hs-CRP values.

PMID- 23134527
TI  - The effect of acute versus delayed remote ischemic preconditioning on reperfusion
      induced ventricular arrhythmias.
AB  - INTRODUCTION: The effect of remote ischemic preconditioning (RIPC) on arrhythmias
      in in vivo models is unknown. Our purpose was to determine effects of both acute
      and delayed RIPC on arrhythmias. METHODS AND RESULTS: In the acute protocol
      anesthetized open chest rats were exposed to 5 minutes of proximal left coronary
      artery occlusion (CAO) and 10 minutes of reperfusion. Rats were either untreated
      (ischemia/reperfusion, IR group, n = 17) or received RIPC (n = 14) with 5 minutes
      bilateral femoral occlusions followed by 5 minutes of reperfusion times 3,
      started 30 minutes before CAO. At reperfusion, onset of ventricular tachycardia
      (VT) was delayed in RIPC group (25.7 seconds) versus IR (8.8 seconds; P = 0.04).
      Number of episodes of VT was 17.0 in IR versus 3.0 in the RIPC group (P = 0.01)
      and duration of VT was 54.1 seconds in IR versus 4.9 seconds in RIPC (P = 0.019).
      Number of ventricular premature complexes (VPC) was 26.0 in IR and 10.0 in RIPC
      rats (P = 0.04). Levels of reperfusion injury salvage kinases (RISK), that is,
      phospho-Akt and phospho-p70S6 in the risk area of IR and RIPC hearts were
      similarly higher compared to the nonischemic areas both at 1 and 10 minutes into
      reperfusion. Delayed RIPC was induced on day 1 and on day 2, myocardial IR was
      induced. Delayed RIPC did not affect VT or VPC. CONCLUSION: Acute RIPC of the
      lower limbs induced a powerful delay in/and reduction in IR induced ventricular
      arrhythmias, but without evoking the RISK pathway; a late protective phase of
      RIPC on arrhythmias did not occur.

PMID- 23134528
TI  - Minimal stimulation protocol using letrozole versus microdose flare up GnRH
      agonist protocol in women with poor ovarian response undergoing ICSI.
AB  - BACKGROUND: To compare the IVF outcomes of letrozole/antagonist and microdose
      GnRH agonist flare up protocols in poor ovarian responders undergoing
      intracytoplasmic sperm injection. MATERIALS AND METHODS: A randomized controlled
      trial was performed in patients with one or more previous failed IVF cycles in
      which four or less oocytes were retrieved when the gonadotrophin starting dose
      was at least 300 IU/day. Sixty patients were randomized by computer-generated
      list to receive either letrozole/antagonist (mild stimulation) n = 30 or GnRH-a
      protocol (microdose flare) n = 30. RESULTS: Both groups were similar with respect
      to background and hormonal characteristics (age, duration of infertility, BMI,
      FSH, LH and E2). The clinical pregnancy rate per cycle was similar in both groups
      (13.3 vs. 16.6%; OR = 0.769; 95% CI = 0.185, 3.198). The doses of used
      gonadotropins and the number of stimulation days were significantly lower in the
      letrozole/antagonist protocol. The peak E2 level on the day of hCG, the
      endometrial thickness, the retrieved oocytes, the number of fertilized oocytes,
      the number of transferred embryos and the cancellation rate were statistically
      similar in both groups. CONCLUSIONS: The letrozole/antagonist protocol is a cost
      effective and patient-friendly protocol that may be used in poor ovarian
      responders for IVF/ICSI.

PMID- 23134529
TI  - Sufficient iodine intake during pregnancy: just do it.

PMID- 23134530
TI  - Hypercoagulability in Cushing's syndrome: prevalence, pathogenesis and treatment.
AB  - Cushing's syndrome is not only accompanied by an increased prevalence of
      cardiovascular disease but also by a hypercoagulable state that is reflected by
      an increased incidence of venous thromboembolism. Overall, patients with CS have
      been reported to have a more than 10-fold increased risk of developing venous
      thromboembolism. Moreover, the incidence of postoperative thrombosis has been
      shown to be comparable to the risk after major orthopaedic surgery.
      Hypercoagulability in CS is due to both increased production of procoagulant
      factors with activation of the coagulation cascade and an impaired fibrinolytic
      capacity, resulting in a shortened activated partial thromboplastin time and an
      increased clot lysis time respectively. Although these abnormalities seem to
      improve 1 year following successful surgery, they do not yet normalize.
      Therefore, sustained biochemical remission might be required to fully resolve the
      hypercoagulable state in CS. Considering the risk of venous thromboembolism in
      uncontrolled CS there may be a rationale to give patients with active CS
      thromboprophylaxis. So far this seems warranted following surgical interventions.
      However, further studies are needed to determine the optimal dosage and duration
      of thromboprophylaxis.

PMID- 23134531
TI  - Characteristics of low-temperature plasma ionization for ambient mass
      spectrometry compared to electrospray ionization and atmospheric pressure
      chemical ionization.
AB  - Ambient desorption/ionization mass spectrometry (ADI-MS) is an attractive method
      for direct analysis with applications in homeland security, forensics, and human
      health. For example, low-temperature plasma probe (LTP) ionization was
      successfully used to detect, e.g., explosives, drugs, and pesticides directly on
      the target. Despite the fact that the field is gaining significant attention, few
      attempts have been made to classify ambient ionization techniques based on their
      ionization characteristics and performance compared to conventional ionization
      sources used in mass spectrometry. In the present study, relative ionization
      efficiencies (RIEs) for a large group of compound families were determined with
      LTP-Orbitrap-MS and compared to those obtained with electrospray ionization mass
      spectrometry (ESI-MS) and atmospheric pressure chemical ionization mass
      spectrometry (APCI-MS). RIEs were normalized against one reference compound used
      across all methods to ensure comparability of the results. Typically, LTP analyte
      ionization through protonation/deprotonation (e.g., 4-acetamidophenol) was
      observed; in some cases (e.g., acenaphthene) radicals were formed. Amines,
      amides, and aldehydes were ionized successfully with LTP. A benefit of LTP over
      conventional methods is the possibility to successfully ionize PAHs and imides.
      Here, the studied model compounds could be detected by neither APCI nor ESI. LTP
      is a relatively soft ionization method because little fragmentation of model
      compounds was observed. It is considered to be an attractive method for the
      ionization of low molecular weight compounds over a relatively wide polarity
      range.

PMID- 23134532
TI  - Metabolic profile, enzyme kinetics, and reaction phenotyping of beta-lapachone
      metabolism in human liver and intestine in vitro.
AB  - beta-Lapachone (beta-Lap) is an NAD(P)H: quinone oxidoreductase 1 (NQO1) target
      antitumor drug candidate in phase II clinical trials. The present study aimed to
      uncover the metabolic profile, enzyme kinetics, and enzyme isoforms for the
      metabolism of beta-Lap in human liver and intestine in vitro. NQO1-mediated
      quinone reduction and subsequent glucuronidation is the predominant metabolic
      pathway for beta-Lap in humans; a pair of regioisomers (M1 and M2) of reduced
      beta-Lap glucuronides were the major metabolites found from human S9 incubations.
      The overall glucuronidation clearance of beta-Lap in human liver S9 was 4754.90
      MUL/min/mg of protein and was 8.1-fold of that in human intestinal S9.
      Recombinant UDP-glucuronosyltransferase (UGT) screening, correlation analysis,
      enzyme kinetics, and chemical inhibition study were performed to determine the
      UGT isoforms involved in beta-Lap metabolism. UGT1A7, UGT1A8, and UGT1A9 are the
      predominant isoforms responsible for the formation of M2 while UGT2B7 is the main
      isoform for M1, suggesting a regioselective glucuronidation of reduced quinone by
      UGTs. It was of interest to find that beta-Lap underwent nonenzymatic two
      electron reduction, providing a novel explanation for the toxicities of beta-Lap
      to NQO1-negative cells at high concentration and with long-time incubation. In
      conclusion, this study contributes to a better understanding of not only beta-Lap
      metabolism but its antitumor property as well.

PMID- 23134533
TI  - Donation by donors with an atypical pulse rate does not increase the risk of
      cardiac ischaemic events.
AB  - BACKGROUND AND OBJECTIVES: In many jurisdictions, blood donors who have an
      atypical pulse rate are temporarily deferred. This practice is not supported by
      evidence. We evaluated whether accepting donors with an atypical pulse rate
      increases their risk of cardiac ischaemic events. METHODS: We measured the
      cumulative incidence of hospitalizations and deaths for coronary heart disease
      within 1 year of follow-up among donors who, between 2002 and 2006, were
      temporarily deferred because of an atypical pulse (<50 beats/min, >100 beats/min,
      or irregular). We compared this incidence to that observed among donors who also
      had an atypical pulse but who were allowed to donate, following a change in our
      deferral policy in 2007. The occurrence of cardiac events was determined through
      hospital discharge and death registries. RESULTS: Among 6076 donors who were
      temporarily deferred for an atypical pulse, the 1-year rate of hospitalization or
      death for cardiac ischaemic events was 3.5/1000, compared to 2.4 in donors who
      had an atypical pulse but who were allowed to donate (n =10,671), for an adjusted
      odds ratio of 1.7 (95% CI, 0.9-3.0, P=0.08). CONCLUSION: Regardless of the
      clinical significance of an atypical pulse rate, our data show that accepting
      donors with this condition does not increase the occurrence of serious cardiac
      ischaemic events. We conclude that pulse rate measurement in prospective donors
      is not warranted.

PMID- 23134534
TI  - Accelerative and decelerative effects of hedonic valence and emotional arousal
      during visual scene processing.
AB  - Perceptual processing of natural scene pictures is enhanced when the scene
      conveys emotional content. Such "motivated attention" to pleasant and unpleasant
      pictures has been shown to improve identification accuracy in non-speeded
      behavioural tasks. An open question is whether emotional content also modulates
      the speed of visual scene processing. In the present studies we show that
      unpleasant content reliably slowed two-choice categorization of pictures,
      irrespective of physical image properties, perceptual complexity, and
      categorization instructions. Conversely, pleasant content did not slow or even
      accelerated choice reactions, relative to neutral scenes. As indicated by
      lateralized readiness potentials, these effects occurred at cognitive processing
      rather than motor preparation/execution stages. Specifically, analysis of event
      related potentials showed a prolongation of early scene discrimination for
      stimuli perceived as emotionally arousing, regardless of valence, and reflected
      in delayed peaks of the N1 component. In contrast, the timing of other processing
      steps, reflected in the P2 and late positive potential components and presumably
      related to post-discriminatory processes such as stimulus-response mapping,
      appeared to be determined by hedonic valence, with more pleasant scenes eliciting
      faster processing. Consistent with this model, varying arousal (low/high) within
      the emotional categories mediated the effects of valence on choice reaction
      speed. Functionally, arousal may prolong stimulus analysis in order to prevent
      erroneous and potentially harmful decisions. Pleasantness may act as a safety
      signal allowing rapid initiation of overt responses. 

PMID- 23134535
TI  - Synthesis and reactivity of nitrogen nucleophiles-induced cage-rearrangement
      silsesquioxanes.
AB  - Novel phthalimide and o-sulfobenzimide-functionalized silsesquioxanes were
      successfully synthesized via nucleophilic substitution reactions from octakis(3
      chloropropyl)octasilsesquioxane. Surprisingly, the formation of deca- and
      dodecasilsesquioxanes cages was discovered during substitution with phthalimide,
      but only octasilsesquioxane maintained a cage in the o-sulfobenzimide
      substitution reaction. Moreover, we report the electronic effect of nitrogen
      nucleophiles to promote cage-rearrangement of inorganic silsesquioxane core for
      the first time. Structures of products were confirmed by (1)H, (13)C, and (29)Si
      NMR spectroscopy, ESI-MS analysis, and single-crystal X-ray diffraction. 

PMID- 23134536
TI  - Addressing challenges in bipolar diagnosis: what do good clinicians already do?
      An editorial comment to Phelps J, Ghaemi SN 'The mistaken claim of bipolar
      'overdiagnosis': solving the false positives problem for DSM-5/ICD-11'.

PMID- 23134537
TI  - Tandem catalysis for the preparation of cylindrical polypeptide brushes.
AB  - Here, we report a method for synthesis of cylindrical copolypeptide brushes via N
      carboxyanhydride (NCA) polymerization utilizing a new tandem catalysis approach
      that allows preparation of brushes with controlled segment lengths in a
      straightforward, one-pot procedure requiring no intermediate isolation or
      purification steps. To obtain high-density brush copolypeptides, we used a
      "grafting from" approach where alloc-alpha-aminoamide groups were installed onto
      the side chains of NCAs to serve as masked initiators. These groups were inert
      during cobalt-initiated NCA polymerization and gave allyloxycarbonyl-alpha
      aminoamide-substituted polypeptide main chains. The alloc-alpha-aminoamide groups
      were then activated in situ using nickel to generate initiators for growth of
      side-chain brush segments. This use of stepwise tandem cobalt and nickel
      catalysis was found to be an efficient method for preparation of high-chain
      density, cylindrical copolypeptide brushes, where both the main chains and side
      chains can be prepared with controlled segment lengths.

PMID- 23134539
TI  - Characterization of a novel EAST-negative enteropathogenic E. coli strain
      implicated in a food-borne outbreak of diarrhoea in adults.
AB  - Enteropathogenic Escherichia coli (EPEC) is usually associated with outbreaks and
      sporadic cases of severe infantile diarrhoea in the developing world, and less
      commonly with sporadic cases in developed countries. Very little evidence
      indicates that EPEC is a food-borne pathogen for adults. In a previous study, two
      groups of adult travellers became ill, and eae(+) E. coli of serogroup O111 was
      isolated from affected individuals and epidemiologically linked to food
      consumption. Here the strain responsible was further investigated and
      characterized as an unusual atypical EPEC. PCR analysis of the designated type
      isolate showed the presence of the rorf1 and espB genes of the LEE pathogenicity
      island, which was inserted at the chromosomal selC locus. The isolate was
      negative for the enteroaggregative E. coli EAST-1 toxin present in other strains
      of EPEC associated with food-borne outbreaks. The strain adhered sparsely to HEp
      2 cell monolayers in a diffuse manner, but fluorescent actin staining
      demonstrated that it was capable of inducing polymerization of actin at the sites
      of bacterial attachment. Strain P2583 is the first EAST-negative EPEC to be
      confirmed as a cause of outbreaks of infection in adults following the
      consumption of contaminated food or water.

PMID- 23134540
TI  - Elective segmental ureterectomy for transitional cell carcinoma of the ureter:
      long-term follow-up in a series of 73 patients.
AB  - What's known on the subject? and What does the study add? Upper Urinary Tract
      (UUT) Transitional Cell Carcinoma (TCC) is an uncommon disease and represents
      approximately 5% of all urothelial carcinomas. We report our series on 73
      patients treated with Kidney Sparing Surgery for UUT TCC. Good results have been
      achieved in terms of oncological outcome comparing this conservative approach to
      the radical nephrourectomy. OBJECTIVES: * To report the long-term oncological
      outcome in patients with transitional cell carcinoma of the ureter electively
      treated with kidney-sparing surgery. * To compare our data with the few series
      reported in the literature. PATIENTS AND METHODS: * We considered 73 patients
      with transitional cell carcinoma of the distal ureter treated in five Italian
      Departments of Urology. * The following surgeries were carried out: 38
      reimplantations on psoas hitch bladder (52%), 21 end-to-end anastomoses (28.8%),
      11 direct ureterocystoneostomies (15.1%) and three reimplantations on Boari flap
      bladder (4.1%). * The median follow-up was 87 months. RESULTS: * Tumours were pTa
      in 42.5% of patients, pT1 in 31.5%, pT2 in 17.8% and pT3 in 8.2%. * Recurrence of
      bladder urothelial carcinoma was found in 10 patients (13.7%) after a median time
      of 28 months. * The bladder recurrence-free survival at 5 years was 82.2%. * The
      overall survival at 5 years was 85.3% and the cancer-specific survival rate at 5
      years was 94.1%. CONCLUSION: * Our data show that segmental ureterectomy
      procedures do not result in worse cancer control compared with data in the
      literature regarding nephroureterectomy.

PMID- 23134541
TI  - Examining the safety of PPAR agonists - current trends and future prospects.
AB  - INTRODUCTION: The peroxisome proliferator-activated receptor (PPAR)-alpha and 
      gamma agonists, fibrates and glitazones, are effective treatments for
      dyslipidemia and type 2 diabetes mellitus, respectively, but exhibit class
      related, as well as compound-specific safety characteristics. AREAS COVERED: This
      article reviews the profiles of PPAR-alpha, PPAR-gamma, and dual PPAR-alpha/gamma
      agonists with regard to class-related and compound-specific efficacy and adverse
      effects. We explore how learnings from first-generation drugs are being applied
      to develop safer PPAR-targeted therapies. EXPERT OPINION: The finding that
      rosiglitazone may increase risk for cardiovascular events has led to regulatory
      guidelines requiring demonstration of cardiovascular safety in appropriate
      outcome trials for new type 2 diabetes mellitus drugs. The emerging data on the
      possibly increased risk of bladder cancer with pioglitazone may prompt the need
      for post-approval safety studies for new drugs. Since PPAR-alpha and -gamma
      affect key cardiometabolic risk factors (diabetic dyslipidemia, insulin
      resistance, hyperglycemia, and inflammation) in a complementary fashion,
      combining their benefits has emerged as a particularly attractive option. New
      PPAR-targeted therapies that balance the relative potency and/or activity toward
      PPAR-alpha and -gamma have shown promise in retaining efficacy while reducing
      potential side effects.

PMID- 23134542
TI  - Theoretical study on CuCl-catalyzed coupling of thiol esters with organostannane.
AB  - The reaction of CuCl-catalyzed coupling of thiol ester with organostannane has
      been theoretically investigated using density functional calculations. This
      reaction takes place with CuCl as a catalyst, giving the product ketone and an
      organotin sulfide. The relatively low overall activation barrier calculated (26.0
      kcal/mol) supports the experimental fact that this reaction proceeds under mild
      reaction conditions. The conversion of the resulting Cu(I) thiolate intermediate
      (D) to the benzoisothiazole (E) was found to proceed via an one-step process. The
      relatively high overall activation barrier calculated (35.8 kcal/mol) supports
      the experimental fact that this reaction proceeds under harsher reaction
      conditions. The influence of hybridization of the carbon atom bonded to sulfur on
      the reaction was also discussed.

PMID- 23134543
TI  - Role flexing: how community, religion, and family shape the experiences of young
      black men who have sex with men.
AB  - While the disproportionate impact of HIV on young black men who have sex with men
      (MSM) is well documented, the reasons for this disparity remain less clear.
      Through in-depth interviews, we explored the role of familial, religious, and
      community influence on the experiences of young black MSM and identified
      strategies that these young men use to negotiate and manage their sexual minority
      status. Between February and April 2008, 16 interviews were conducted among HIV
      infected and HIV-uninfected young (19- to 24-year-old) black MSM in the Jackson,
      Mississippi, area. Results suggest that overall, homosexuality remains highly
      stigmatized by the men's families, religious community, and the African American
      community. To manage this stigma, many of the participants engaged in a process
      of "role flexing," in which individuals modified their behavior in order to adapt
      to a particular situation. The data also provided evidence of internalized
      homophobia among a number of the participants. The impact of stigma on risk
      behavior should be more fully explored, and future intervention efforts need to
      explicitly address and challenge stigma, both among young men themselves and the
      communities in which they reside. Attention should also be paid to the role
      masculinity may play as a driver of the HIV epidemic among young black MSM and
      how this knowledge can be used to inform prevention efforts.

PMID- 23134544
TI  - The guiding of research funding: corrosive competition or stability,
      sustainability and serendipity.

PMID- 23134545
TI  - Celebrating research!

PMID- 23134546
TI  - The survival rate and the risk factors for death among patients with aneurysmal
      subarachnoid haemorrhages.

PMID- 23134547
TI  - Stroke symptoms and risk factor awareness in high school children in Pakistan.

PMID- 23134548
TI  - Activity profiling of vacuolar processing enzymes reveals a role for VPE during
      oomycete infection.
AB  - Vacuolar processing enzymes (VPEs) are important cysteine proteases that are
      implicated in the maturation of seed storage proteins, and programmed cell death
      during plant-microbe interactions and development. Here, we introduce a specific,
      cell-permeable, activity-based probe for VPEs. This probe is highly specific for
      all four Arabidopsis VPEs, and labeling is activity-dependent, as illustrated by
      sensitivity for inhibitors, pH and reducing agents. We show that the probe can be
      used for in vivo imaging and displays multiple active isoforms of VPEs in various
      tissues and in both monocot and dicot plant species. Thus, VPE activity profiling
      is a robust, simple and powerful tool for plant research for a wide range of
      applications. Using VPE activity profiling, we discovered that VPE activity is
      increased during infection with the oomycete pathogen Hyaloperonospora
      arabidopsidis (Hpa). The enhanced VPE activity is host-derived and EDS1
      independent. Sporulation of Hpa is reduced on vpe mutant plants, demonstrating a
      role for VPE during compatible interactions that is presumably independent of
      programmed cell death. Our data indicate that, as an obligate biotroph, Hpa takes
      advantage of increased VPE activity in the host, e.g. to mediate protein turnover
      and nutrient release.

PMID- 23134549
TI  - Protection from procedural myocardial injury by omega-3 polyunsaturated fatty
      acids (PUFAs): is related with lower levels of creatine kinase-MB (CK-MB) and
      troponin I?
AB  - OBJECTIVE: This study sought to investigate the effect of omega-3 polyunsaturated
      fatty acids (PUFAs) on cardiac biomarkers, CK-MB, and troponin I in patients
      undergoing PCI. BACKGROUND: Restenosis remains as a major long-term complication
      following percutaneous coronary intervention (PCI). It appears that there is
      strong relationship between post-PCI creatine kinase-MB (CK-MB) and troponin I
      elevation and cardiovascular events after PCI. METHODS: In this randomized
      clinical trial, a total of 90 patients planned to undergo PCI were randomly
      assigned into two groups: Group A-receiving omega-3 PUFAs (3 g, 12 h before PCI)
      plus standard treatment (n = 43) and Group B-control group, receiving only
      standard therapy (n = 47). Standard treatment included aspirin 325 mg and
      clopidogrel 600 mg loading dose. The plasma CK-MB level was measured before the
      procedure (baseline), at 8 and 24 h after PCI. The plasma troponin I was measured
      at baseline and 24 h after PCI. RESULTS: In comparison with control, omega-3
      PUFAs could significantly reduce the level of CK-MB in 8 (P = 0.001) and 24 h (P
      = 0.012) after its prescription in the omega-3 PUFAs group. Omega-3 PUFAs could
      not significantly decrease troponin I. CONCLUSION: Our results revealed that
      omega-3 PUFAs can be considered as a safe adjunctive medication to the standard
      regimen before PCI for the aim of decreasing cardiovascular event after PCI.

PMID- 23134550
TI  - Negative affect promotes encoding of and memory for details at the expense of the
      gist: affect, encoding, and false memories.
AB  - I investigated whether negative affective states enhance encoding of and memory
      for item-specific information reducing false memories. Positive, negative, and
      neutral moods were induced, and participants then completed a Deese-Roediger
      McDermott (DRM) false-memory task. List items were presented in unique spatial
      locations or unique fonts to serve as measures for item-specific encoding. The
      negative mood conditions had more accurate memories for item-specific
      information, and they also had fewer false memories. The final experiment used a
      manipulation that drew attention to distinctive information, which aided learning
      for DRM words, but also promoted item-specific encoding. For the condition that
      promoted item-specific encoding, false memories were reduced for positive and
      neutral mood conditions to a rate similar to that of the negative mood condition.
      These experiments demonstrated that negative affective cues promote item-specific
      processing reducing false memories. People in positive and negative moods encode
      events differently creating different memories for the same event. 

PMID- 23134551
TI  - Variability of protein and phosphoprotein levels in clinical tissue specimens
      during the preanalytical phase.
AB  - The quality of human tissue specimens can have a significant impact on analytical
      data sets for biomarker research. The aim of this study was to characterize
      fluctuations of protein and phosphoprotein levels in human tissue samples during
      the preanalytical phase. Eleven intestine and 17 liver specimens were surgically
      resected, aliquoted, and either snap-frozen or fixed in formalin immediately or
      exposed to different ischemic conditions before preservation. Protein levels in
      the resultant samples were investigated by reverse phase protein array, Western
      blot analysis, and liquid chromatography-tandem mass spectrometry. Our data
      revealed that the degree of sensitivity of proteins and phosphoproteins to
      delayed preservation varied between different patients and tissue types. For
      example, up-regulation of phospho-p42/44 MAPK in intestine samples was seen in
      some patients but not in others. General trends toward up- or down-regulation of
      most proteins were not evident due to pronounced interpatient variability but
      signal intensities of only a few proteins, such as cytokeratin 18, were altered
      from baseline in postresection samples. In contrast, glyceraldehyde 3-phosphate
      dehydrogenase was found to be stable during periods of cold ischemia. Our study
      represents a proper approach for studying potential protein fluctuations in
      tissue specimens for future biomarker development programs.

PMID- 23134552
TI  - Unraveling the mechanism of electrospray ionization.
AB  - Electrospray ionization (ESI) generates intact gas-phase ions from analytes in
      solution for mass spectrometric investigations. ESI can proceed via different
      mechanisms. Low molecular weight analytes follow the ion evaporation model (IEM),
      whereas the charged residue model (CRM) applies to large globular species. A
      chain ejection model (CEM) has been proposed for disordered polymers.

PMID- 23134553
TI  - The first case of association between postpartum thyroiditis and thyroid hormone
      resistance in an Italian patient showing a novel p.V283A THRB mutation.
AB  - BACKGROUND: Postpartum thyroiditis (PPT) is characterized by the development of
      postpartum thyroid dysfunction, which may occur up to 12 months after delivery.
      The syndrome usually presents with transient thyrotoxicosis, followed by
      transient hypothyroidism. The association of this condition with resistance to
      thyroid hormones (RTH) has never been described. PATIENT FINDINGS: In this
      report, we describe a 30-year-old patient affected by RTH due to a novel p.V283A
      thyroid hormone receptor-beta (THRB) heterozygous mutation in exon 8, which
      affects the ligand-binding domain, never before described in literature. A simple
      polymorphism was excluded through screening of 100 healthy controls. SUMMARY: The
      patient became pregnant twice (in 2008 and in 2009) and developed PPT after both
      deliveries. Two months after her first pregnancy and one month after her second
      pregnancy, she presented with severe endogenous thyrotoxicosis and concomitant
      suppressed thyrotropin (TSH) levels, which represents an unusual finding in
      patients affected by RTH. Other causes of hyperthyroidism were excluded. After
      the hyperthyroid phase, she became hypothyroid (TSH >75 mU/L and low free
      thyroxine and free-tri-iodothyronine levels), and eventually returned to her
      usual euthyroid status. During the course of PPT, no specific treatment was
      required, except for beta-blockers used to treat tachycardia during the
      hyperthyroid phase. CONCLUSIONS: We report a unique case of a woman affected by
      RTH, due to a novel mutation V283A in THRB, who experienced PPT with a severe
      thyrotoxic phase after both her pregnancies. The association between RTH and PPT
      has never been reported in the literature. In particular, the marked suppression
      of TSH occurring when levels of TH are particularly elevated is not a frequent
      condition during RTH.

PMID- 23134554
TI  - Endoscopic treatment for biliary stricture after orthotopic liver
      transplantation: success, recurrence and their influencing factors.
AB  - OBJECTIVE: To investigate the success and recurrence rates and factors
      influencing the effect of endoscopic therapy for patients with biliary stricture
      after orthotopic liver transplantation (OLT). METHODS: Data of 56 patients who
      underwent endoscopic therapy for biliary stricture after OLT from 2006 to 2009
      were reviewed in this study. Their clinical data, laboratory parameters and
      endoscopic features were recorded. RESULTS: Biliary stricture was treated
      successfully in 47 patients (83.9%). Compared with those with treatment failure,
      there was a longer duration from OLT to initial presentations (P = 0.02) in the
      successful group, fewer endoscopic retrograde cholangiopancreatography (ERCP)
      treatments (P < 0.01) and fewer stents inserted per patient (P < 0.01).
      Multivariate analysis showed that the number of ERCP treatments per patient was
      negatively related with treatment success. Of the 47 patients successfully
      treated, stricture recurred in 13 (27.7%) during follow-up. Compared with those
      without recurrence, the recurrence group had a shorter initial presentation time
      after OLT, higher serum alanine aminotransferase, aspartate aminotransferase and
      gamma-glutamyltransferase levels, higher numbers of ERCP treatments and stents
      used and a longer duration of treatment (P < 0.01 for all). Multivariate analysis
      showed that the treatment duration was a risk factor for recurrence (OR 2.33, 95%
      CI 1.34-4.05, P < 0.01). CONCLUSIONS: Endoscopic treatment is a safe and
      effective modality for biliary stricture after OLT. The number of ERCP treatments
      per patient is negatively related with treatment success and long treatment
      duration was a risk factor for stricture recurrence.

PMID- 23134555
TI  - Enhancement of meristem formation by bouquet-1, a mis-sense allele of the
      vernalization independence 3 gene encoding a WD40 repeat protein in Arabidopsis
      thaliana.
AB  - In higher plants, the shoot apical meristem (SAM) is the ultimate source
      supplying cells that constitute the aboveground tissues and organs. The cells
      supplied from the SAM begin to proliferate rapidly and then concomitantly start
      to differentiate. We identified a novel mutant, named bouquet-1 (boq-1),
      exhibiting highly pleiotropic shoot growth phenotypes. The boq-1 plants showed an
      increase in the inflorescence stem number accompanied by frequent fasciation.
      This particular phenotype appeared to be due to the development of extra SAMs in
      a shoot meristemless (STM)-dependent manner. Expression of STM was also expanded
      widely in the boq-1 shoot apex, suggesting that the repressive state of the STM
      transcription may not be established or maintained, leading to the misexpression.
      Molecular cloning of the relevant gene showed that the BOQ gene encodes a WD40
      repeat protein, which has been reported as vernalization independence 3 (VIP3).
      In addition, the finding that overproduction of the boq-1 allele in the wild-type
      background mimicked the boq-1 phenotypes in a dose-dependent manner suggested
      that the mutant BOQ-1 protein acts in a dominant negative manner. Taking these
      results together, we propose that the boq-1 mutation affects the proper
      progression of cell differentiation process.

PMID- 23134556
TI  - Component pathogen inactivation: a critical review.
AB  - BACKGROUND AND OBJECTIVES: Pathogen inactivation (PI)-treated plasma and
      platelets are increasingly becoming the products of choice, where licensed. This
      review summarizes the clinical evidence available for licensed component PI
      technologies and red cell PI under development. MATERIALS AND METHODS: Available
      literature on licensed technologies was reviewed. RESULTS: For the plasma and
      platelets technologies available, evidence for the inactivation of most pathogens
      is good, except for certain nonenveloped viruses. Clinical trials and
      haemovigilance programmes suggest the observed loss of potency is of little
      clinical significance, with some technology-specific exceptions. Concerns over
      adverse toxicological effects or neoantigen formation have not been confirmed for
      currently licensed products. CONCLUSION: While platelet PI has been adopted to
      reduce bacterial contamination, the ability of PI methods to replace testing for
      emerging bloodborne infections, or as a substitute for selective pathogen
      testing, gamma-irradiation or even leucodepletion, make adoption of PI for
      components increasingly attractive.

PMID- 23134557
TI  - ACTH-secreting Crooke cell carcinoma of the pituitary.
AB  - PURPOSE: While pituitary adenomas are common, pituitary carcinomas are rare. It
      is unclear whether pituitary carcinomas arise de novo or evolve from adenomas.
      METHODS: We studied the clinical characteristics and tissue samples from eight
      pituitary surgeries and the autopsy from a patient with pituitary carcinoma. A 16
      year-old female patient was diagnosed with an aggressive Crooke cell
      macroadenoma. Following transsphenoidal surgery, clinical signs of Cushing
      disease quickly reappeared. During the 14-year course of the illness, eight
      pituitary surgeries, three courses of extracranial irradiation and two (90)
      Yttrium-DOTATOC treatments were undertaken. A bilateral adrenalectomy was
      performed. The patient died of metastatic disease and uncontrolled
      hypercortisolism due to an adrenal remnant. A systematic morphologic study
      (histologic staining, electron microscopy) of all available surgical and autopsy
      specimens was undertaken. RESULTS: Brisk mitotic activity, high Ki-67 and p53
      immunolabelling were present in the pituitary samples from the onset. High
      proportion of tumour cells showed irregular nuclei and large nucleoli, and
      gradual increase in MGMT staining was observed. The tumour remained of Crooke
      cell type throughout the course. Autopsy disclosed a postirradiation sarcoma in
      the pituitary area. CONCLUSIONS: The question whether pituitary carcinomas arise
      de novo or transform from an adenoma cannot be answered at present with
      certainty.

PMID- 23134558
TI  - Efficacy of the levonorgestrel intrauterine system (LNG-IUS) in the prevention of
      the atypical endometrial hyperplasia and endometrial cancer: retrospective data
      from selected obese menopausal symptomatic women.
AB  - The aim of this retrospective study was to evaluate the efficacy of
      levonorgestrel intrauterine system-releasing (LNG-IUS) insertion in preventing
      atypical endometrial hyperplasia (AH) and endometrial cancer (EC) in symptomatic
      postmenopausal overweight/obese women. A total of 34 overweight/obese
      postmenopausal women, presenting abnormal uterine bleeding (AUB) and endometrial
      hyperplasia (EH), and who were submitted to LNG-IUS insertion, were identified
      from registry data. Endometrial histology at LNG-IUS insertion showed simple EH
      in 20 cases (58.8%), complex EH in 14 cases (41.2%). At 36 months, 91% of
      patients showed no recurrence of AUB and a significant reduction in the mean
      endometrial thickness (from 8.2 +/- 2.2 to 3.2 +/- 1.5 mm, p < 0.05) was
      observed. Histologic regression of EH was observed in 27 (79.4%) and 33 (97.5%)
      cases at 12 and 36 months, respectively. None of the women in which EH persisted,
      reported cellular atypia or cancer progression at 12 and 36 months of follow-up.
      LNG-IUS represents an effective treatment option to manage postmenopausal obese
      women affected by AUB and EH. The device seems to be able to prevent the onset of
      AH and EC in women at high risk. Further prospective controlled studies in a well
      selected group of women are needed.

PMID- 23134561
TI  - Dicyanogermylenes: a tale of isomers and interconversions.
AB  - A systematic investigation is carried out using the B3LYP, BLYP, and BHLYP
      functionals and MP2 level of theory to characterize the low-lying electronic
      singlet and triplet GeC2N2 isomers. The basis sets used are of double-zeta plus
      polarization quality with additional s- and p-type diffuse functions, DZP++.
      Three bent isomers Ge(CN)2, CNGeCN, and Ge(NC)2 are located on the singlet and
      triplet potential energy surfaces. In visualizing the reaction pathways for the
      singlet isomerization of the bent isomers, two three-membered [Ge, C, N] cyclic
      systems, with exocyclic -C-C=N and -C-N=C bonding, appear on the energy surface.
      Four types of electron affinities reported are: the adiabatic electron affinity,
      the zero-point vibrationally corrected electron affinity, the vertical electron
      affinity, and the vertical detachment energy of the anion. The ionization
      energies and singlet-triplet gaps for all isomers are also reported. The
      energetic ordering (kcal mol(-1)) (B3LYP) with zero-point vibrational energy
      corrections for the singlet ground state isomers follows: Ge(CN)2 (global
      minimum) < CNGeCN (2.3) < Ge(NC)2 (3.3) < Cyc_exo_CCN (15.3) < Cyc_exo_CNC
      (30.6). All the bent and cyclic isomers are found to be below the dissociation
      limit to Ge ((3)P) + C2N2 ((1)Sigmag). The rate constants for all
      interconversions are evaluated using transition state theory. 

PMID- 23134559
TI  - Treating depression within the HIV "medical home": a guided algorithm for
      antidepressant management by HIV clinicians.
AB  - People living with HIV/AIDS (PLWHA) suffer increased depression prevalence
      compared to the general population, which negatively impacts antiretroviral (ART)
      adherence and HIV-related outcomes leading to morbidity and mortality. Yet
      depression in this population often goes undiagnosed and untreated. The current
      project sought to design an evidence-based approach to integrate depression care
      in HIV clinics. The model chosen, measurement-based care (MBC), is based on
      existing guidelines and the largest randomized trial of depression treatment. MBC
      was adapted to clinical realities of HIV care for use in a randomized controlled
      effectiveness trial of depression management at three academic HIV clinics. The
      adaptation accounts for drug-drug interactions critical to ongoing ART
      effectiveness and can be delivered by a multidisciplinary team of nonmental
      health providers. A treatment algorithm was developed that enables clinically
      supervised, nonphysician depression care managers (DCMs) to track and monitor
      antidepressant tolerability and treatment response while supporting
      nonpsychiatric prescribers with antidepressant choice and dosing. Quality of care
      is ensured through weekly supervision of DCMs by psychiatrists. Key areas of
      flexibility that have been important in implementation have included flexibility
      in timing of assessments, accommodation of divergence between algorithm
      recommendations and provider decisions, and accommodation of delays in
      implementing treatment plans. This adaptation of the MBC model to HIV care has
      accounted for critical antidepressant-antiretroviral interactions and facilitated
      the provision of quality antidepressant management within the HIV medical home.

PMID- 23134563
TI  - Habitual snoring and atopic state: correlations with respiratory function and
      teeth occlusion.
AB  - BACKGROUND: Allergy represents a risk factor at the base of sleep-disordered
      breathing in pediatric age. Among allergic diseases, the atopy is characterized
      by a tendency to be "hyperallergic." Sleep-disordered breathing is also known in
      orthodontics as correlated with the morphology of craniofacial complex. The aim
      of this study was to investigate the relation between atopy and sleep-disordered
      breathing (oral breathers with habitual snoring), comparing atopic children with
      sleep-disordered breathing (test group) with nonatopic ones with sleep-disordered
      breathing (control group), in the prevalence of dento-skeletal alterations and
      other risk factors that trigger sleep-disordered breathing, such as
      adenotonsillar hypertrophy, turbinate hypertrophy, obesity, and alteration of
      oxygen arterial saturation. METHODS: In a group of 110 subjects with sleep
      disordered breathing (6 to 12 years old), we grouped the subjects into atopic
      (test group, 60 subjects) and nonatopic (control group, 50 subjects) children and
      compared the data on the following: skin allergic tests, rhinoscopy,
      rhinomanometry, night home pulsoxymetry, body mass index, and dento-facial
      alterations. RESULTS: Even if our results suggest that atopy is not a direct risk
      factor for sleep-disordered breathing, the importance of a physiologic nasal
      respiration in the pathogenesis of sleep-disordered breathing seems to be
      demonstrated in our study by the higher prevalence of hypertrophy in the
      adenotonsillar lymphatic tissue, odontostomatological alterations, alterations of
      the oxygen saturation to pulsoxymetry, and higher prevalence of obesity observed
      in our children with sleep-disordered breathing, in percentages higher than that
      of the general pediatric population previously observed in the literature.
      CONCLUSIONS: The importance of a physiologic nasal respiration in the
      pathogenesis of sleep-disordered breathing is demonstrated in our study.

PMID- 23134564
TI  - Nonverbal signals speak up: association between perceptual nonverbal dominance
      and emotional intelligence.
AB  - Emotional communication uses verbal and nonverbal means. In case of conflicting
      signals, nonverbal information is assumed to have a stronger impact. It is
      unclear, however, whether perceptual nonverbal dominance varies between
      individuals and whether it is linked to emotional intelligence. Using audiovisual
      stimulus material comprising verbal and nonverbal emotional cues that were varied
      independently, perceptual nonverbal dominance profiles and their relations to
      emotional intelligence were examined. Nonverbal dominance was found in every
      participant, ranging from 55 to 100%. Moreover, emotional intelligence,
      particularly the ability to understand emotions, correlated positively with
      nonverbal dominance. Furthermore, higher overall emotional intelligence as well
      as a higher ability to understand emotions were linked to smaller reaction time
      differences between emotionally incongruent and congruent stimuli. The
      association between perceptual nonverbal dominance and emotional intelligence,
      and more specifically the ability to understand emotions, might reflect an
      adaptive process driven by the experience of higher authenticity in nonverbal
      cues. 

PMID- 23134565
TI  - Design and testing of a synthetic biology framework for genetic engineering of
      Corynebacterium glutamicum.
AB  - BACKGROUND: Synthetic biology approaches can make a significant contribution to
      the advance of metabolic engineering by reducing the development time of
      recombinant organisms. However, most of synthetic biology tools have been
      developed for Escherichia coli. Here we provide a platform for rapid engineering
      of C. glutamicum, a microorganism of great industrial interest. This bacteria,
      used for decades for the fermentative production of amino acids, has recently
      been developed as a host for the production of several economically important
      compounds including metabolites and recombinant proteins because of its higher
      capacity of secretion compared to traditional bacterial hosts like E. coli. Thus,
      the development of modern molecular platforms may significantly contribute to
      establish C. glutamicum as a robust and versatile microbial factory. RESULTS: A
      plasmid based platform named pTGR was created where all the genetic components
      are flanked by unique restriction sites to both facilitate the evaluation of
      regulatory sequences and the assembly of constructs for the expression of
      multiple genes. The approach was validated by using reporter genes to test
      promoters, ribosome binding sites, and for the assembly of dual gene operons and
      gene clusters containing two transcriptional units. Combinatorial assembly of
      promoter (tac, cspB and sod) and RBS (lacZ, cspB and sod) elements with different
      strengths conferred clear differential gene expression of two reporter genes,
      eGFP and mCherry, thus allowing transcriptional "fine-tuning"of multiple genes.
      In addition, the platform allowed the rapid assembly of operons and genes
      clusters for co-expression of heterologous genes, a feature that may assist
      metabolic pathway engineering. CONCLUSIONS: We anticipate that the pTGR platform
      will contribute to explore the potential of novel parts to regulate gene
      expression, and to facilitate the assembly of genetic circuits for metabolic
      engineering of C. glutamicum. The standardization provided by this approach may
      provide a means to improve the productivity of biosynthetic pathways in microbial
      factories for the production of novel compounds.

PMID- 23134566
TI  - Characterization of microflora in Latin-style cheeses by next-generation
      sequencing technology.
AB  - BACKGROUND: Cheese contamination can occur at numerous stages in the
      manufacturing process including the use of improperly pasteurized or raw milk. Of
      concern is the potential contamination by Listeria monocytogenes and other
      pathogenic bacteria that find the high moisture levels and moderate pH of popular
      Latin-style cheeses like queso fresco a hospitable environment. In the
      investigation of a foodborne outbreak, samples typically undergo enrichment in
      broth for 24 hours followed by selective agar plating to isolate bacterial
      colonies for confirmatory testing. The broth enrichment step may also enable
      background microflora to proliferate, which can confound subsequent analysis if
      not inhibited by effective broth or agar additives. We used 16S rRNA gene
      sequencing to provide a preliminary survey of bacterial species associated with
      three brands of Latin-style cheeses after 24-hour broth enrichment. RESULTS:
      Brand A showed a greater diversity than the other two cheese brands (Brands B and
      C) at nearly every taxonomic level except phylum. Brand B showed the least
      diversity and was dominated by a single bacterial taxon, Exiguobacterium, not
      previously reported in cheese. This genus was also found in Brand C, although
      Lactococcus was prominent, an expected finding since this bacteria belongs to the
      group of lactic acid bacteria (LAB) commonly found in fermented foods.
      CONCLUSIONS: The contrasting diversity observed in Latin-style cheese was
      surprising, demonstrating that despite similarity of cheese type, raw materials
      and cheese making conditions appear to play a critical role in the microflora
      composition of the final product. The high bacterial diversity associated with
      Brand A suggests it may have been prepared with raw materials of high bacterial
      diversity or influenced by the ecology of the processing environment.
      Additionally, the presence of Exiguobacterium in high proportions (96%) in Brand
      B and, to a lesser extent, Brand C (46%), may have been influenced by the
      enrichment process. This study is the first to define Latin-style cheese
      microflora using Next-Generation Sequencing. These valuable preliminary data will
      direct selective tailoring of agar formulations to improve culture-based
      detection of pathogens in Latin-style cheese.

PMID- 23134567
TI  - Theoretical study on the ground state structure of uranofullerene U@C82.
AB  - Despite its experimental characterization, the detailed geometry and electronic
      structure of actinide metallofullerene U@C(82) have been rarely studied. We
      predict that (#5)C(82) and (#8)C(82) are the best cages for the encapsulation of
      monovalent and tetravalent U (i.e., U(+) and U(4+)), respectively; while
      (#9)C(82) is the best cage for divalent, trivalent, pentavalent, and hexavalent U
      cations (i.e., U(2+), U(3+), U(5+), and U(6+)). U@(#9)C(82) is the
      thermodynamically most stable one among all the isomers and thus corresponds to
      the most experimentally isolable isomer of U@C(82). The calculated spin density
      explicitly suggests that the endohedral metallofullerene U@(#9)C(82) is a
      trivalent ion-pair with an electronic configuration of U(3+)@C(82)(3-). The
      proposed geometry and electronic structure of U(3+)@(#9)C(82)(3-) are in good
      agreement with the experimental observation.

PMID- 23134568
TI  - The tomato cis-prenyltransferase gene family.
AB  - cis-prenyltransferases (CPTs) are predicted to be involved in the synthesis of
      long-chain polyisoprenoids, all with five or more isoprene (C5) units. Recently,
      we identified a short-chain CPT, neryl diphosphate synthase (NDPS1), in tomato
      (Solanum lycopersicum). Here, we searched the tomato genome and identified and
      characterized its entire CPT gene family, which comprises seven members (SlCPT1
      7, with NDPS1 designated as SlCPT1). Six of the SlCPT genes encode proteins with
      N-terminal targeting sequences, which, when fused to GFP, mediated GFP transport
      to the plastids of Arabidopsis protoplasts. The SlCPT3-GFP fusion protein was
      localized to the cytosol. Enzymatic characterization of recombinant SlCPT
      proteins demonstrated that SlCPT6 produces Z,Z-FPP, and SlCPT2 catalyzes the
      formation of nerylneryl diphosphate while SlCPT4, SlCPT5 and SlCPT7 synthesize
      longer-chain products (C25-C55). Although no in vitro activity was demonstrated
      for SlCPT3, its expression in the Saccharomyces cerevisiae dolichol biosynthesis
      mutant (rer2) complemented the temperature-sensitive growth defect. Transcripts
      of SlCPT2, SlCPT4, SlCPT5 and SlCPT7 are present at low levels in multiple
      tissues, SlCPT6 is exclusively expressed in red fruit and roots, and SlCPT1,
      SlCPT3 and SlCPT7 are highly expressed in trichomes. RNAi-mediated suppression of
      NDPS1 led to a large decrease in beta-phellandrene (which is produced from neryl
      diphosphate), with greater reductions achieved with the general 35S promoter
      compared to the trichome-specific MKS1 promoter. Phylogenetic analysis revealed
      CPT gene families in both eudicots and monocots, and showed that all the short
      chain CPT genes from tomato (SlCPT1, SlCPT2 and SlCPT6) are closely linked to
      terpene synthase gene clusters.

PMID- 23134569
TI  - Elective segmental ureterectomy for transitional cell carcinoma of the ureter:
      long-term follow-up in a series of 73 patients.

PMID- 23134570
TI  - Immunogenicity and safety of a 2009 pandemic influenza A (H1N1) monovalent
      vaccine in Chinese infants aged 6-35 months: a randomized, double-blind,
      controlled phase I clinical trial.
AB  - OBJECTIVES: The goal of this double-blind, randomized, controlled clinical trial
      was to assess the safety and immunogenicity of two different doses of a
      monovalent split-virion 2009 pandemic influenza A/H1N1 vaccine without adjuvant
      in Chinese infants aged 6-35 months. DESIGN AND SETTING  Subjects were randomly
      assigned to receive either a 2009 pandemic (H1N1) vaccine containing 7.5 or 15
      MUg haemagglutinin (HA) or a seasonal influenza vaccine. 2 doses of the H1N1
      vaccines or the seasonal influenza vaccine were given 21 days apart in younger
      infants aged 6-23 months or older infants aged 24-35 months. SAMPLE: Serum
      samples were collected immediately before the first injection and before and 21
      days after the second injection. MAIN OUTCOME MEASURES: Primary outcomes were
      haemagglutinin inhibition (HI) antibody responses 21 days following each
      vaccination. Safety was monitoring throughout the study. RESULTS: The first
      vaccination of 7.5 MUg and 15 MUg H1N1 vaccine induced seroprotective antibody
      titers (HI titers>=1: 40) in 42.9-57.4% of younger infants and 49.1-61.0% older
      infants. Immune responses after completion of the two dose schedule were
      comparable in both age groups with seroprotective rates of 91-98% in each vaccine
      and age group and GMTs of 173-263. The H1N1 vaccine elicited similar rates of
      local and systemic adverse reactions as the seasonal influenza vaccine.
      CONCLUSIONS: The 2009 pandemic influenza A /H1N1 vaccine were highly immunogenic
      in infants aged 6-35 months, and displayed a safety and reactogenicity profile
      similar to the seasonal influenza vaccine. TRIAL REGISTRATION: ClinicalTrial.gov
      identifier: NCT01047202.

PMID- 23134571
TI  - Searching joint association signals in CATIE schizophrenia genome-wide
      association studies through a refined integrative network approach.
AB  - BACKGROUND: Genome-wide association studies (GWAS) have generated a wealth of
      valuable genotyping data for complex diseases/traits. A large proportion of these
      data are embedded with many weakly associated markers that have been missed in
      traditional single marker analyses, but they may provide valuable insights in
      dissecting the genetic components of diseases. Gene set analysis (GSA) augmented
      by protein-protein interaction network data provides a promising way to examine
      GWAS data by analyzing the combined effects of multiple genes/markers, each of
      which may have only individually weak to moderate association effects. A critical
      issue in GSA of GWAS data is the definition of gene-wise P values based on
      multiple SNPs mapped to a gene. RESULTS: In this study, we proposed an
      alternative restricted search approach based on our previously developed dense
      module search algorithm, and we demonstrated it in the CATIE GWAS dataset for
      schizophrenia. Specifically, we explored three ways of computing gene-wise P
      values and examined their effects on the resultant module genes. These methods
      calculate gene-wise P values based on all the SNPs, the top ranked SNPs, or the
      most significant SNP among all the SNPs mapped to a gene. We applied the
      restricted search approach and identified a module gene set for each of the gene
      wise P value data set. In our evaluation using an independent method, ALIGATOR,
      we showed that although each of these input datasets generated a unique set of
      module genes, all of them were significant in the GWAS dataset. Further
      functional enrichment analysis of these module genes showed that at the pathway
      level, they were all consistently related to neuro- and immune-related pathways.
      Finally, we compared our method with a previously reported method. CONCLUSION:
      Our results showed that the approaches to computing gene-wise P values in GWAS
      data are critical in GSA. This work is useful for evaluating key factors in GSA
      of GWAS data.

PMID- 23134572
TI  - Evidence for Vpr-dependent HIV-1 replication in human CD4+ CEM.NKR T-cells.
AB  - BACKGROUND: Vpr is exclusively expressed in primate lentiviruses and contributes
      to viral replication and disease progression in vivo. HIV-1 Vpr has two major
      activities in vitro: arrest of cell cycle in the G2 phase (G2 arrest), and
      enhancement of viral replication in macrophages. Previously, we reported a potent
      HIV-1 restriction in the human CD4+ CEM.NKR (NKR) T cells, where wild-type (WT)
      HIV-1 replication was inhibited by almost 1,000-fold. From the parental NKR
      cells, we isolated eight clones by limiting dilution. These clones showed three
      levels of resistance to the WT HIV-1 infection: non-permissive (NP), semi
      permissive (SP), and permissive (P). Here, we compared the replication of WT, Vif
      defective, Vpr-defective, and Vpu-defective viruses in these cells. RESULTS:
      Although both WT and Vpu-defective viruses could replicate in the permissive and
      semi-permissive clones, the replication of Vif-defective and Vpr-defective
      viruses was completely restricted. The expression of APOBEC3G (A3G) cytidine
      deaminase in NKR cells explains why Vif, but not Vpr, was required for HIV-1
      replication. When the Vpr-defective virus life cycle was compared with the WT
      virus life cycle in the semi-permissive cells, it was found that the Vpr
      defective virus could enter the cell and produce virions containing properly
      processed Gag and Env proteins, but these virions showed much less efficiency for
      reverse transcription during the next-round of infection. In addition, although
      viral replication was restricted in the non-permissive cells, treatment with
      arsenic trioxide (As2O3) could completely restore WT, but not Vpr-defective virus
      replication. Moreover, disruption of Vpr binding to its cofactor DCAF1 and/or
      induction of G2 arrest activity did not disrupt the Vpr activity in enhancing HIV
      1 replication in NKR cells. CONCLUSIONS: These results demonstrate that HIV-1
      replication in NKR cells is Vpr-dependent. Vpr promotes HIV-1 replication from
      the 2nd cycle likely by overcoming a block at early stage of viral replication;
      and this activity does not require DCAF1 and G2 arrest. Further studies of this
      mechanism should provide new understanding of Vpr function in the HIV-1 life
      cycle.

PMID- 23134573
TI  - Polyethyleneimine-templated Ag nanoclusters: a new fluorescent and colorimetric
      platform for sensitive and selective sensing halide ions and high disturbance
      tolerant recognitions of iodide and bromide in coexistence with chloride under
      condition of high ionic strength.
AB  - Ag nanoclusters functioned by hyperbranched polyethyleneimine have been developed
      as a new fluorescent and colorimetric platform for sensitive and selective
      recognition of halide ions (e.g., Cl(-), Br(-), and I(-)). The recognition
      mechanism is based on the unique reactions between halide ions and the silver
      atoms. In particular, halide-induced oxidative etching and aggregation can
      produce a strong fluorescence quenching of Ag nanoclusters. This sensing system
      exhibits a remarkably high selectivity toward halide ions over most of anions and
      cations and shows good linear ranges and lower detection limits: the linear
      ranges are 0.5-80 MUM for Cl(-), 0.1-14 MUM for Br(-), and 0.05-6 MUM for I(-),
      respectively; the limits of detection for Cl(-), Br(-), and I(-), at a signal-to
      noise ratio of 3, are estimated to be 200, 65, and 40 nM, respectively.
      Specifically, Br(-) and I(-) could be recognized selectively in the coexistence
      with Cl(-) under the condition of higher ionic strength, which is a significant
      advantage in the detection of Br(-) and I(-) in real samples. In addition, the
      recognition of halide could be performed by the colorimetric method, which is
      also attractive and promising because of its simplicity, rapidity, reliability,
      and low cost. Furthermore, this sensing system has been applied successfully to
      the detection of Cl(-) in real water samples.

PMID- 23134574
TI  - Social network analysis for assessment of avian influenza spread and trading
      patterns of backyard chickens in Nakhon Pathom, Suphan Buri and Ratchaburi,
      Thailand.
AB  - The aim of this study is to explain the social networks of the backyard chicken
      in Ratchaburi, Suphan Buri and Nakhon Pathom Provinces. In this study, we
      designed the nodes as groups of persons or places involved in activities relating
      to backyard chickens. The ties are all activities related to the nodes. The study
      applied a partial network approach to assess the spreading pattern of avian
      influenza. From 557 questionnaires collected from the nodes, the researchers
      found that the degree (the numbers of ties that a node has) and closeness (the
      distance from one node to the others) centralities of Nakhon Pathom were
      significantly higher than those of the others (P<0.001). The results show that
      compared with the remaining areas, this area is more quickly connected to many
      links. If the avian influenza virus subtype H5N1 was released into the network,
      the disease would spread throughout this province more rapidly than in Ratchaburi
      and Suphan Buri. The betweenness centrality in each of these provinces showed no
      differences (P>0.05). In this study, the nodes that play an important role in all
      networks are farmers who raise consumable chicken, farmers who raise both
      consumable chicken and fighting cocks, farmers' households that connect with
      dominant nodes, and the owners and observers of fighting cocks at arenas and
      training fields. In this study, we did not find cut points or blocks in the
      network. Moreover, we detected a random network in all provinces. Thus,
      connectivity between the nodes covers long or short distances, with less
      predictable behaviour. Finally, this study suggests that activities between the
      important nodes must receive special attention for disease control during future
      disease outbreaks.

PMID- 23134575
TI  - Intradermal sex hormone desensitization for relief of premenstrual symptoms may
      improve the obstetric outcome of women with recurrent pregnancy loss.
AB  - The aim of this study was to determine whether women with recurrent pregnancy
      loss (RPL) and concurrent premenstrual syndrome (PMS) who underwent
      desensitization with sex hormones had an improved obstetric outcome. This
      manuscript summarizes a 10 year open label prospective follow up study of 26
      women with RPL, aged 25-42 with 3-8 previous miscarriages and PMS, who had
      hormone hypersensitivity on skin testing. Skin testing was positive to estradiol
      in 23 women, progesterone in 20 women and to both estrogen and progesterone in 17
      women. Amelioration of the symptoms of PMS (according to the VAS) was seen in 21
      of 26 patients after desensitization with small doses of sex hormones
      intradermally. There was long term and stable reduction of severe PMS in 21 of 26
      patients after desensitization. Five women conceived after skin testing, prior to
      desensitization. Sixteen of 26 women (61%) had subsequent live births. Five women
      had two subsequent live births in the subsequent pregnancy. There were no
      obstetric complications. Five women had two subsequent pregnancies with live
      births. It seems that correction of sex hormone hypersensitivity was accompanied
      by relief of persistent PMS, may have a positive effect on the chances of a
      successful pregnancy.

PMID- 23134576
TI  - Gonadotropin treatment augments postnatal oogenesis and primordial follicle
      assembly in adult mouse ovaries?
AB  - BACKGROUND: Follicle stimulating hormone (FSH) exerts action on both germline and
      somatic compartment in both ovary and testis although FSH receptors (FSHR) are
      localized only on the somatic cells namely granulosa cells of growing follicles
      and Sertoli cells in the seminiferous tubules. High levels of FSH in females are
      associated with poor ovarian reserve, ovarian hyper stimulation syndrome etc. and
      at the same time FSH acts as a survival factor during in vitro organotypic
      culture of ovarian cortical strips. Thus a further understanding of FSH action on
      the ovary is essential. We have earlier reported presence of pluripotent very
      small embryonic-like stem cells (VSELs express Oct-4A in addition to other
      pluripotent markers) and their immediate descendants 'progenitors' ovarian germ
      stem cells (OGSCs express Oct-4B in addition to other germ cell markers) in
      ovarian surface epithelium (OSE) in various mammalian species including mice,
      rabbit, monkey, sheep and human. Present study was undertaken to investigate the
      effect of pregnant mare serum gonadotropin (PMSG) on adult mice ovaries with a
      focus on VSELs, OGSCs, postnatal oogenesis and primordial follicle assembly.
      METHODS: Ovaries were collected from adult mice during different stages of estrus
      cycle and after 2 and 7 days of PMSG (5 IU) treatment to study histo-architecture
      and expression for FSHR, pluripotent stem cells , meiosis and germ cell specific
      markers. RESULTS: PMSG treatment resulted in increased FSHR and proliferation as
      indicated by increased FSHR and PCNA immunostaining in OSE and oocytes of
      primordial follicles (PF) besides the granulosa cells of large antral follicles.
      Small 1-2 regions of multilayered OSE invariably associated with a cohort of PF
      during estrus stage in control ovary were increased to 5-8 regions after PMSG
      treatment. This was associated with an increase in pluripotent transcripts (Oct
      4A, Nanog), meiosis (Scp-3) and germ cells (Oct-4B, Mvh) specific markers. MVH
      showed positive immuno staining on germ cell nest-like clusters and at places
      primordial follicles appeared connected through oocytes. CONCLUSIONS: The results
      of the present study show that gonadotropin (PMSG) treatment to adult mouse leads
      to increased pluripotent stem cell activity in the ovaries, associated with
      increased meiosis, appearance of several cohorts of PF and their assembly in
      close proximity of OSE. This was found associated with the presence of germ cell
      nests and cytoplasmic continuity of oocytes in PF. We have earlier reported that
      pluripotent ovarian stem cells in the adult mammalian ovary are the VSELs which
      give rise to slightly differentiated OGSCs. Thus we propose that gonadotropin
      through its action on pluripotent VSELs augments neo-oogenesis and PF assembly in
      adult mouse ovaries.

PMID- 23134577
TI  - TNF/TNFR signal transduction pathway-mediated anti-apoptosis and anti
      inflammatory effects of sodium ferulate on IL-1beta-induced rat osteoarthritis
      chondrocytes in vitro.
AB  - INTRODUCTION: Sodium ferulate (SF) is a natural component of traditional Chinese
      herbs. Our previous study shows that SF has a protective effect on osteoarthritis
      (OA). The objective of this study was to investigate the effect of SF on the
      TNF/TNF receptor (TNFR) signal transduction pathway of rat OA chondrocytes.
      METHODS: Primary rat articular chondrocytes were co-treated with IL-1beta and SF.
      Chondrocyte apoptosis was assessed by fluorescein isothiocyanate-annexin
      V/propidium iodide assay. The PCR array was used to screen the expression of 84
      key genes involved in apoptosis. The release of TNFalpha and prostaglandin E2
      were analyzed by ELISA. Expressions of proteins were assessed by western
      blotting. The activity of NF-kappaB was determined by electrophoretic mobility
      shift assay (EMSA). Gene expression of inducible nitric oxide synthase (iNOS) was
      evaluated by real-time quantitative PCR. The nitric oxide content was measured
      with the Griess method. RESULTS: After treatment with SF, the apoptosis rate of
      chondrocytes significantly attenuated (P < 0.01). Results of the apoptosis PCR
      array suggested that mRNA expression of some core proteins in the TNF/TNFR
      pathway showed valuable regulation. The protein expressions of TNFalpha, TNFR-1,
      TNF receptor-associated death domain, caspase-8 and caspase-3 were prevented by
      SF in a concentration-dependent manner. SF also inhibited activities of caspase-8
      and caspase-3 compared with the OA model control (P < 0.01). TNF receptor
      associated factor-2 expression, phosphorylations of inhibitor of NF-kappaB kinase
      (IKK) subunits alpha and beta, and NF-kappaB inhibitor, alpha (IkappaBalpha) were
      all concentration-dependently suppressed by SF treatment. The results of EMSA
      showed that SF inhibited the activity of NF-kappaB. In addition, the expressions
      of cycloxygenase-2 and iNOS and the contents of prostaglandin E2 and NO were
      attenuated with the treatment of SF (P < 0.01). CONCLUSION: SF has anti-apoptosis
      and anti-inflammatory effects on an OA model induced by IL-1beta in vitro, which
      were due to inhibitory actions on the caspase-dependent apoptosis pathway and the
      IKK/NF-kappaB signal transduction pathway of the TNF/TNFR pathway.

PMID- 23134578
TI  - Non-permissive C6/36 cell culture for the Australian isolate of Macrobrachium
      rosenbergii nodavirus.
AB  - Macrobrachium rosenbergii nodavirus (MrNV) that causes white tail disease (WTD)
      is an emerging disease that contributes to serious production losses in
      Macrobrachium hatcheries worldwide. Mosquito cell lines (C6/36) have been
      reported to support the growth of MrNV and used to observe the cytopathic effects
      (CPE) in infected cells. This study determined the susceptibility of C6/36
      mosquito cells to the Australian isolate of MrNV in order to use fewer animals in
      further investigations. Different staining methods were used to observe MrNV
      viral activity in C6/36 cells. Typical cytopathic effects such as vacuolation and
      viral inclusion bodies were observed in infected C6/36 cells with H&E and Giemsa
      staining. With acridine orange, it was easier to detect presumptive MrNV
      messenger ribonucleic acid in the infected cells. Using neutral red staining to
      measure mitochondrial activity showed light absorption of infected cells
      maximized at day 4 (O.D. = 0.6) but was significantly lower (chi-square = 41.265,
      df = 1, P < 0.05) than control groups (O.D. = 2) which maximized at day 12. Using
      trypan blue staining to count the number of cells with disrupted cell membranes,
      the maximum number of presumptively dead cells at day 8 (4 * 10(5)  cells) in
      infected treatments was higher than the control treatment at day 10 (1.8 * 10(5) 
      cells). However, TaqMan real-time PCR did not confirm the replication of MrNV in
      the cells over 14 days. The mean viral copies and mean cycle times of positive
      samples were stable at 2.07 * 10(4) and 24.12, respectively. Limited evidence of
      viral replication was observed during four serial passages. This study determined
      the mortality of the C6/36 cell line to the Australian isolate of MrNV but
      suggests limited patent replication was occurring. Trying different cell lines or
      adapting the virus to the C6/36 cells may be necessary to successfully replicate
      Australian MrNV in cell lines.

PMID- 23134579
TI  - Panchromic cationic iridium(III) complexes.
AB  - We report the synthesis, X-ray structures, and optoelectronic characterization of
      two cationic iridium complexes bearing bis[(4-methoxyphenyl)imino]acenaphthene
      ligands. These complexes exhibited panchromic absorption extending as far as 800
      nm, making them of interest for solar-energy-harvesting applications. 

PMID- 23134580
TI  - Beliefs about medicine and illness are associated with fear of cancer recurrence
      in women taking adjuvant endocrine therapy for breast cancer.
AB  - OBJECTIVES: Adjuvant endocrine therapy for early-stage breast cancer has greatly
      reduced the morbidity and mortality associated with breast cancer recurrence.
      Despite this, a significant proportion of women report fears of cancer
      recurrence. This study examined the associations between fear of cancer
      recurrence (FoR) and illness perceptions, medication beliefs, and treatment side
      effects in women taking adjuvant endocrine therapy following breast cancer.
      METHODS: A total of 153 post-menopausal women with early-stage breast cancer
      completed a postal survey. Analyses were conducted to examine the association
      between FoR and illness perceptions, medication beliefs, treatment side effects,
      demographic factors, and emotional distress and to identify which of these
      factors would be most strongly associated with FoR in a regression model.
      RESULTS: All illness perceptions (apart from personal control) were associated
      with FoR, as were patient beliefs about endocrine therapy. Although treatment
      side effects, being unemployed, and higher levels of anxiety and depression were
      associated with FoR, only illness perceptions (identity, treatment control,
      timeline, and emotional representation) and medication necessity beliefs were
      significantly correlated with FoR in the final model. CONCLUSIONS: It appears
      that, in addition to directly targeting FoR, it may be worthwhile to address the
      illness and medication beliefs supporting the fear. Additionally, helping women
      to differentiate everyday symptoms from those indicative of breast cancer may
      help to reduce fear of recurrence. STATEMENT OF CONTRIBUTION: What is already
      known on this subject? A significant proportion of women report fear of cancer
      recurrence following breast cancer. The literature shows that illness
      perceptions, side effects of treatment, and beliefs about medicines are related
      to fear of recurrence among cancer patients. However, because these variables
      have often been looked at in isolation, it is not clear whether some perceptions
      or cues are more likely to relate to fear of recurrence than others. What does
      this study add? This study shows illness perceptions and medication beliefs are
      strongly related to fears of cancer recurrence. The results point to ways in
      which the self-regulatory model of illness may be used to reduce patients' fear
      of recurrence. The study results show that women with higher fear of recurrence
      may be balancing a tension between believing that they need to take the
      medication to protect their future health alongside concerns that the treatment
      may not be working.

PMID- 23134581
TI  - Efficacy of flexible spectral imaging color enhancement on the detection of small
      intestinal diseases by capsule endoscopy.
AB  - OBJECTIVE: The aim of this study was to estimate the efficacy of flexible
      spectral imaging color enhancement (FICE) on the detection of small intestinal
      diseases by capsule endoscopy (CE). METHODS: Six individuals without significant
      lesions and 18 patients with following diseases were selected: four tumors, five
      angioectasias, seven ulcerative diseases, one ulcerative lesion and tumor and one
      ulcerative lesion and angioectasia. Three endoscopists reviewed all CE videos on
      standard and three types of FICE modes and compared their sensitivity and
      specificity for detection of small intestinal diseases. RESULTS: The overall
      sensitivity of CE was 94.4% at standard mode, 90.7% at FICE channel (Ch) 1, 87.0%
      at FICE Ch 2 and 87.0% at FICE Ch 3 and the overall specificity of CE was 66.7%,
      55.6%, 77.8% and 66.7%, respectively, per patient. There was no significant
      difference between the standard and each FICE mode. In per-lesion analysis, FICE
      Ch 1 detected more angioectasias and ulcerative lesions than the standard mode
      (angioectasia, 25.7 vs 21.0, P = 0.005; ulcerative lesions, 19.3 vs 14.0, P =
      0.06). However, FICE Ch 1 missed more tumors than the standard mode (4.3 vs 10.0,
      P = 0.003). CONCLUSIONS: Although FICE Ch 1 is better in detecting angioectasias
      and ulcerative lesions and worse in tumors or polyps than the standard mode, the
      patient-based sensitivity and specificity of small intestinal diseases are not
      different between standard and each FICE mode. Further experiences with and
      improvement of FICE are required.

PMID- 23134582
TI  - Inflammatory prognostic markers in clear cell renal cell carcinoma - preoperative
      C-reactive protein does not improve predictive accuracy.
AB  - What's known on the subject? and What does the study add? White blood cell count
      and C-reactive protein are reliable prognostic RCC Biomarkers.Nevertheless,
      accepted cut-offs for risk stratifications are missing. Therefore, both
      parameters were re-evaluated and multivariable analyses revealed an optimal CRP
      breakpoint at 0.25 mg/dL to be best to stratify patients at risk of cancer
      specific mortality. However, this CRP-based prediction added no additional
      information compared to a clinico-pathological based model. OBJECTIVE: To re
      evaluate the prognostic and predictive significance of the preoperative white
      blood cell (WBC) count and C-reactive protein (CRP) that independently predicts
      patient prognosis and to determine optimal threshold values for CRP. PATIENTS AND
      METHODS: From 1996 to 2005, 327 patients with surgery for clear cell renal cell
      carcinoma were retrospectively evaluated. Cox proportional hazard models were
      used, adjusted for the effects of tumour stage, size, Fuhrman grade and Karnofsky
      index, to evaluate the prognostic significance of WBC count and CRP and to
      identify threshold values. Identified thresholds were correlated with
      clinicopathological parameters and used to estimate cancer-specific survival. To
      prove any additional predictive accuracy of the identified threshold it was
      compared with a clinicopathological base model using the Harrell concordance
      index (c-index). RESULTS: In univariable analyses WBC count was a significant
      prognostic marker at a concentration of 9.5/MUL (hazard ratio [HR] 1.83) and
      11.0/MUL (HR 2.09) and supported CRP values of 0.25 mg/dL (HR 6.47, P < 0.001)
      and 0.5 mg/dL (HR 7.15, P < 0.001) as potential threshold values. If adjusted by
      the multivariable models WBC count showed no clear breakpoint, but a CRP value of
      0.25 mg/dL (HR 2.80, P = 0.027) proved to be optimal. Reduced cancer-specific
      survival was proved for CRP 0.25 mg/dL (median 69.9 vs 92.3 months). Median
      follow-up was 57.5 months with 72 (22%) tumour-related deaths. The final model
      built by the addition of CRP 0.25 mg/dL did not improve predictive accuracy (c
      index 0.877) compared with the clinicopathological base model (c-index 0.881)
      which included TNM stage, grading and Karnofsky index. CONCLUSIONS: Multivariable
      analyses revealed that an optimal breakpoint of CRP at a value of 0.25 mg/dL was
      best to stratify patients at risk of cancer-specific mortality, but CRP 0.25
      mg/dL added no additional information in the prediction model. Therefore we
      cannot recommend measuring CRP as the traditional parameters of TNM stage,
      grading and Karnofsky index are already of high predictive accuracy.

PMID- 23134583
TI  - Oxidized LDL receptor 1 gene polymorphism in patients with metabolic syndrome.
AB  - AIMS: The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1),
      encoded by the OLR1 gene, has been implicated in the pathogenesis of
      atherosclerosis. We therefore evaluated the genotyping of OLR1 gene in a sample
      of 55 patients with Metabolic Syndrome, a clinical condition characterized by a
      high cardiovascular risk. METHODS AND PATIENTS: The genotyping of the LOX-1 was
      performed by polymerase chain reaction (PCR) analysis of the IVS4-14 A>G OLR1
      polymorphism embedded within the OLR1 Linkage Disequilibrium block. Patients were
      assessed for routine serum parameters, microalbuminuria, insulin resistance
      (HOMA) and oxidative stress (thiobarbituric acid reactive substances, TBARs and
      thioredoxin). RESULTS: The allele or genotype distribution of the OLR1 IVS4-14
      A>G was not statistically different between MS and controls subjects. A positive
      association was found between IVS4-14 GG genotype, microalbuminuria and fasting
      glycaemia as well as a higher frequency of type 2 diabetes, elevated
      microalbuminuria, fasting serum glucose and HOMA index in the same subjects.
      Thioredoxin values were higher in patients with MS but did not differ in relation
      to OLR1 IVS4-14 A>G genotype. The TBARs/Cholesterol ratio was higher in MS both
      in IVS4-14 GG and in IVS4-14 AG. CONCLUSION: IVS4-14 GG genotype seems to be
      related to glucose metabolism disturbance, elevated insulin level and lipid
      peroxidation in patients with MS.

PMID- 23134584
TI  - Hydrogen bonding in neutral and cation dimers of H2Se with H2O, H2S, and H2Se.
AB  - Structures, hydrogen bonding, and binding energies of H(4)SeA (A = O, S, Se)
      dimers and their cation radicals have been studied using DFT-B3LYP, MP2, and CCSD
      methods with 6-31++G(d,p), cc-pVTZ, and aug-cc-pVTZ basis sets. The binding
      energy (BE) order of the most stable neutral and cationic dimers have been found
      to be (H(2)Se...HOH) > (H(2)Se...HSH) > (H(2)Se...HSeH), and (H(2)Se...SeH(2))(+)
      > (H(2)Se...SH(2))(+) > (HSe...HOH(2))(+), respectively, by B3LYP/6-31++G(d,p)
      and MP2/aug-cc-pVTZ methods. Higher electronegativity of the heteroatom has been
      found to result in more stability of the neutral dimer but less of the cationic
      dimer. Among neutral dimers, structure with more electronegative heteroatom
      acting as proton donor has been found to be more stable. However, the hemibonded
      structure has been found to be more stable for the dimer cation radical unless
      the ionization potentials of the involved heteroatoms are very different, e.g.,
      H(4)SeO(+). Vibrational frequency calculation suggests that an increase in
      electronegativity of A-atom results in a decrease in Se-H bond strength in
      H(4)SeA and H(4)SeA(+) dimers. The calculated values of Mulliken atomic
      charge/spin and hydrogen bond lengths of the dimers and their radical cations
      have also been discussed.

PMID- 23134585
TI  - Insect herbivores selectively suppress the HPL branch of the oxylipin pathway in
      host plants.
AB  - Insect herbivores have developed a myriad of strategies to manipulate the defense
      responses of their host plants. Here we provide evidence that chewing insects
      differentially alter the oxylipin profiles produced by the two main and competing
      branches of the plant defensive response pathway, the allene oxide synthase (AOS)
      and hydroperoxide lyase (HPL) branches, which are responsible for wound-inducible
      production of jasmonates (JAs), and green leafy volatiles (GLVs) respectively.
      Specifically, we used three Arabidopsis genotypes that were damaged by mechanical
      wounding or by insects of various feeding guilds (piercing aphids, generalist
      chewing caterpillars and specialist chewing caterpillars). We established that
      emission of GLVs is stimulated by wounding incurred mechanically or by aphids,
      but release of these volatiles is constitutively impaired by both generalist and
      specialist chewing insects. Simultaneously, however, these chewing herbivores
      stimulated JA production, demonstrating targeted insect suppression of the HPL
      branch of the oxylipin pathway. Use of lines engineered to express HPL
      constitutively, in conjunction with quantitative RT-PCR-based expression
      analyses, established a combination of transcriptional and post-transcriptional
      reprogramming of the HPL pathway genes as the mechanistic basis of insect
      mediated suppression of the corresponding metabolites. Feeding studies suggested
      a potential evolutionary advantage of suppressing GLV production, as caterpillars
      preferably consumed leaf tissue from plants that had not been primed by these
      volatile cues.

PMID- 23134586
TI  - On the move? Echinococcus multilocularis in red foxes of Saxony-Anhalt (Germany).
AB  - Echinococcus multilocularis is a cestode parasites that frequently occurs in the
      red fox (Vulpes vulpes), which is the main definitive host in Central Europe. The
      parasite may infect humans as accidental intermediate hosts and cause alveolar
      echinococcosis. In the German federal state of Saxony-Anhalt, the occurrence of
      E. multilocularis in red foxes as a possible source of infection for humans was
      studied from 1998 to 2010. A significant shift in the geographical centroid of
      the occurrence of E. multilocularis from a long-known highly endemic area in the
      southwest of the state towards the north-northeast (3.2 km/year) was found. The
      overall prevalence in the state increased significantly from 13.6% (1998-2005) to
      23.4% (2006-2010). No autochthonous cases of alveolar echinococcosis have been
      reported to date in Saxony-Anhalt, but this might change in the near future with
      the spread and increasing biomass of the parasite.

PMID- 23134587
TI  - A case for molecular recognition in nuclear separations: sulfate separation from
      nuclear wastes.
AB  - In this paper, we present the case for molecular-recognition approaches for
      sulfate removal from radioactive wastes via the use of anion-sequestering systems
      selective for sulfate, using either liquid-liquid extraction or crystallization.
      Potential benefits of removing sulfate from the waste include improved
      vitrification of the waste, reduced waste-form volume, and higher waste-form
      performance, all of which lead to potential cleanup schedule acceleration and
      cost savings. The need for sulfate removal from radioactive waste, especially
      legacy tank wastes stored at the Hanford site, is reviewed in detail and
      primarily relates to the low solubility of sulfate in borosilicate glass.
      Traditional methods applicable to the separation of sulfate from radioactive
      wastes are also reviewed, with the finding that currently no technology has been
      identified and successfully demonstrated to meet this need. Fundamental research
      in the authors' laboratories targeting sulfate as an important representative of
      the class of oxoanions is based on the hypothesis that designed receptors may
      provide the needed ability to recognize sulfate under highly competitive
      conditions, in particular where the nitrate anion concentration is high.
      Receptors that have been shown to have promising affinity for sulfate, either in
      extraction or in crystallization experiments, include hexaurea tripods,
      tetraamide macrocycles, cyclo[8]pyrroles, calixpyrroles, and self-assembled urea
      lined cages. Good sulfate selectivity observed in the laboratory provides
      experimental support for the proposed molecular-recognition approach.

PMID- 23134588
TI  - Health status and health care experiences among homeless patients in federally
      supported health centers: findings from the 2009 patient survey.
AB  - OBJECTIVE: To examine health status and health care experiences of homeless
      patients in health centers and to compare them with their nonhomeless
      counterparts. DATA SOURCES/STUDY SETTING: Nationally representative data from the
      2009 Health Center Patient Survey. STUDY DESIGN: Cross-sectional analyses were
      limited to adults (n = 2,683). We compared sociodemographic characteristics,
      health conditions, access to health care, and utilization of services among
      homeless and nonhomeless patients. We also examined the independent effect of
      homelessness on health care access and utilization, as well as factors that
      influenced homeless patients' health care experiences. DATA COLLECTION: Computer
      assisted personal interviews were conducted with health center patients.
      PRINCIPAL FINDINGS: Homeless patients had worse health status-lifetime burden of
      chronic conditions, mental health problems, and substance use problems-compared
      with housed respondents. In adjusted analyses, homeless patients had twice the
      odds as housed patients of having unmet medical care needs in the past year (OR =
      1.98, 95 percent CI: 1.24-3.16) and twice the odds of having an ED visit in the
      past year (OR = 2.00, 95 percent CI: 1.37-2.92). CONCLUSIONS: There is an ongoing
      need to focus on the health issues that disproportionately affect homeless
      populations. Among health center patients, homelessness is an independent risk
      factor for unmet medical needs and ED use.

PMID- 23134589
TI  - Dasatinib, nilotinib and standard-dose imatinib for the first-line treatment of
      chronic myeloid leukaemia: systematic reviews and economic analyses.
AB  - BACKGROUND: Nilotinib and dasatinib are now being considered as alternative
      treatments to imatinib as a first-line treatment of chronic myeloid leukaemia
      (CML). OBJECTIVE: This technology assessment reviews the available evidence for
      the clinical effectiveness and cost-effectiveness of dasatinib, nilotinib and
      standard-dose imatinib for the first-line treatment of Philadelphia chromosome
      positive CML. DATA SOURCES: Databases [including MEDLINE (Ovid), EMBASE, Current
      Controlled Trials, ClinicalTrials.gov, the US Food and Drug Administration
      website and the European Medicines Agency website] were searched from search end
      date of the last technology appraisal report on this topic in October 2002 to
      September 2011. REVIEW METHODS: A systematic review of clinical effectiveness and
      cost-effectiveness studies; a review of surrogate relationships with survival; a
      review and critique of manufacturer submissions; and a model-based economic
      analysis. RESULTS: Two clinical trials (dasatinib vs imatinib and nilotinib vs
      imatinib) were included in the effectiveness review. Survival was not
      significantly different for dasatinib or nilotinib compared with imatinib with
      the 24-month follow-up data available. The rates of complete cytogenetic response
      (CCyR) and major molecular response (MMR) were higher for patients receiving
      dasatinib than for those with imatinib for 12 months' follow-up (CCyR 83% vs 72%,
      p < 0.001; MMR 46% vs 28%, p < 0.0001). The rates of CCyR and MMR were higher for
      patients receiving nilotinib than for those receiving imatinib for 12 months'
      follow-up (CCyR 80% vs 65%, p < 0.001; MMR 44% vs 22%, p < 0.0001). An indirect
      comparison analysis showed no difference between dasatinib and nilotinib for CCyR
      or MMR rates for 12 months' follow-up (CCyR, odds ratio 1.09, 95% CI 0.61 to
      1.92; MMR, odds ratio 1.28, 95% CI 0.77 to 2.16). There is observational
      association evidence from imatinib studies supporting the use of CCyR and MMR at
      12 months as surrogates for overall all-cause survival and progression-free
      survival in patients with CML in chronic phase. In the cost-effectiveness
      modelling scenario, analyses were provided to reflect the extensive structural
      uncertainty and different approaches to estimating OS. First-line dasatinib is
      predicted to provide very poor value for money compared with first-line imatinib,
      with deterministic incremental cost-effectiveness ratios (ICERs) of between
      L256,000 and L450,000 per quality-adjusted life-year (QALY). Conversely, first
      line nilotinib provided favourable ICERs at the willingness-to-pay threshold of
      L20,000-30,000 per QALY. LIMITATIONS: Immaturity of empirical trial data relative
      to life expectancy, forcing either reliance on surrogate relationships or
      cumulative survival/treatment duration assumptions. CONCLUSIONS: From the two
      trials available, dasatinib and nilotinib have a statistically significant
      advantage compared with imatinib as measured by MMR or CCyR. Taking into account
      the treatment pathways for patients with CML, i.e. assuming the use of second
      line nilotinib, first-line nilotinib appears to be more cost-effective than first
      line imatinib. Dasatinib was not cost-effective if decision thresholds of L20,000
      per QALY or L30,000 per QALY were used, compared with imatinib and nilotinib.
      Uncertainty in the cost-effectiveness analysis would be substantially reduced
      with better and more UK-specific data on the incidence and cost of stem cell
      transplantation in patients with chronic CML. FUNDING: The Health Technology
      Assessment Programme of the National Institute for Health Research.

PMID- 23134590
TI  - The role of A20 in the pathogenesis of lymphocytic malignancy.
AB  - Autoimmune phenomena were identified in many different cases of hematological
      diseases and solid tumors, which may be due to alterations in the expression and
      function of the NF-kappaB signaling pathway. Recently, a number of studies have
      shown that the deletion or mutation of A20, a negative regulator of NF-kappaB, is
      frequently found in lymphomas, suggesting that it may be a linker between the
      altered immune response and leukemogenesis. The aim of this review is to
      summarize current findings of the A20 biological functions and its molecular
      mechanism as a tumor suppressor and immune regulator. The identification of A20
      mutations and deletions in lymphocytic malignancy and the predictive significance
      of these aberrations are also reviewed.

PMID- 23134591
TI  - Longitudinal diffusion tensor imaging in amyotrophic lateral sclerosis.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative
      disorder, caused by progressive loss of motor neurons. Changes are widespread in
      the subcortical white matter in ALS. Diffusion tensor imaging (DTI) detects
      pathological changes in white matter fibres in vivo, based on alterations in the
      degree (diffusivity, ADC) and directedness (fractional anisotropy, FA) of proton
      movement. METHODS: 24 patients with ALS and 24 age-matched controls received 1.5T
      DTI. FA and ADC were analyzed using statistical parametric mapping. In 15 of the
      24 ALS patients, a second DTI was obtained after 6 months. RESULTS: Decreased FA
      in the corticospinal tract (CST) and frontal areas confirm existing results. With
      a direct comparison of baseline and follow-up dataset, the progression of upper
      motor neuron degeneration, reflected in FA decrease, could be captured along the
      CST and in frontal areas. The involvement of cerebellum in the pathology of ALS,
      as suspected from functional MRI studies, could be confirmed by a reduced FA
      (culmen, declive). These structural changes correlated well with disease
      duration, ALSFRS-R, and physical and executive functions. CONCLUSION: DTI detects
      changes that are regarded as prominent features of ALS and thus, shows promise in
      its function as a biomarker. Using the technique herein, we could demonstrate DTI
      changes at follow-up which correlated well with clinical progression.

PMID- 23134592
TI  - 1H-pyrrolo[3,2-h]quinoline: a benchmark molecule for reliable calculations of
      vibrational frequencies, IR intensities, and Raman activities.
AB  - Reliable assignment of 55 out of 57 vibrational modes has been achieved for 1H
      pyrrolo[3,2-h]quinoline using IR, Raman, and fluorescence spectroscopy combined
      with quantum chemical calculations. The experiments provided a data set for
      assessing the performance of different models/basis sets for predicting the
      vibrational frequencies, as well as IR and Raman intensities for a molecule with
      13 heavy atoms. Among six different tested DFT functionals, the hybrid B3LYP used
      with Pople's split-valence basis sets is suggested as the best choice for
      accurate and cost-effective IR/Raman spectral simulations. Neither HF nor MP2
      methods can satisfactorily describe the vibrational structure. Increasing the
      basis set size from double to triple-zeta and by adding polarization and diffuse
      functions does not necessarily improve the results, especially regarding the
      predictions of vibrational frequencies. With respect to the intensities,
      extending the basis set helps, with the accuracy increasing systematically for
      the Raman spectra, and in a less regular fashion for the IR. A large difference
      in accuracy is observed while comparing the spectral parameters predicted for in
      plane and out-of-plane normal modes. The former are reliably computed with modest
      basis sets, whereas for the out-of-plane vibrations, larger basis sets are
      necessary, but even in this case, the out-of-plane vibrations are reproduced with
      much less accuracy than in-plane modes. This effect is general, as it has been
      observed using different functionals and basis sets.

PMID- 23134593
TI  - Effects of multiple conformers per compound upon 3-D similarity search and
      bioassay data analysis.
AB  - BACKGROUND: To improve the utility of PubChem, a public repository containing
      biological activities of small molecules, the PubChem3D project adds
      computationally-derived three-dimensional (3-D) descriptions to the small
      molecule records contained in the PubChem Compound database and provides various
      search and analysis tools that exploit 3-D molecular similarity. Therefore, the
      efficient use of PubChem3D resources requires an understanding of the statistical
      and biological meaning of computed 3-D molecular similarity scores between
      molecules. RESULTS: The present study investigated effects of employing multiple
      conformers per compound upon the 3-D similarity scores between ten thousand
      randomly selected biologically-tested compounds (10-K set) and between non
      inactive compounds in a given biological assay (156-K set). When the "best
      conformer-pair" approach, in which a 3-D similarity score between two compounds
      is represented by the greatest similarity score among all possible conformer
      pairs arising from a compound pair, was employed with ten diverse conformers per
      compound, the average 3-D similarity scores for the 10-K set increased by 0.11,
      0.09, 0.15, 0.16, 0.07, and 0.18 for STST-opt, CTST-opt, ComboTST-opt, STCT-opt,
      CTCT-opt, and ComboTCT-opt, respectively, relative to the corresponding averages
      computed using a single conformer per compound. Interestingly, the best-conformer
      pair approach also increased the average 3-D similarity scores for the non
      inactive-non-inactive (NN) pairs for a given assay, by comparable amounts to
      those for the random compound pairs, although some assays showed a pronounced
      increase in the per-assay NN-pair 3-D similarity scores, compared to the average
      increase for the random compound pairs. CONCLUSION: These results suggest that
      the use of ten diverse conformers per compound in PubChem bioassay data analysis
      using 3-D molecular similarity is not expected to increase the separation of non
      inactive from random and inactive spaces "on average", although some assays show
      a noticeable separation between the non-inactive and random spaces when multiple
      conformers are used for each compound. The present study is a critical next step
      to understand effects of conformational diversity of the molecules upon the 3-D
      molecular similarity and its application to biological activity data analysis in
      PubChem. The results of this study may be helpful to build search and analysis
      tools that exploit 3-D molecular similarity between compounds archived in PubChem
      and other molecular libraries in a more efficient way.

PMID- 23134594
TI  - Association between obesity indices and cardiovascular risk factors in late
      adolescence in the Seychelles.
AB  - BACKGROUND: The ability of different obesity indices to predict cardiovascular
      risk is still debated in youth and few data are available in sub Saharan Africa.
      We compared the associations between several indices of obesity and
      cardiovascular risk factors (CVRFs) in late adolescence in the Seychelles.
      METHODS: We measured body mass index (BMI), waist circumference, waist/hip ratio
      (WHiR), waist/height ratio (WHtR) and percent fat mass (by bioimpedance) and 6
      CVRFs (blood pressure, LDL-cholesterol, HDL-cholesterol, triglycerides, fasting
      blood glucose and uric acid) in 423 youths aged 19-20 years from the general
      population. RESULTS: The prevalence of overweight/obesity and several CVRFs was
      high, with substantial sex differences. Except for glucose in males and LDL
      cholesterol in females, all obesity indices were associated with CVRFs. BMI
      consistently predicted CVRFs at least as well as the other indices. Linear
      regression on BMI had standardized regression coefficients of 0.25-0.36 for most
      CVRFs (p<0.01) and ROC analysis had an AUC between 60%-75% for most CVRFs. BMI
      also predicted well various combinations of CVRFs: 36% of male and 16% of female
      lean subjects (BMI <P50) had >=2 CVRFs compared to 74% of male and 46% of female
      overweight subjects (BMI >P90). CONCLUSION: There was an elevated prevalence of
      obesity and of several CVRFs in youths in Seychelles. BMI predicted single or
      combined CVRFs at least as well as other simple obesity indices.

PMID- 23134595
TI  - Pandemic influenza A virus codon usage revisited: biases, adaptation and
      implications for vaccine strain development.
AB  - BACKGROUND: Influenza A virus (IAV) is a member of the family Orthomyxoviridae
      and contains eight segments of a single-stranded RNA genome with negative
      polarity. The first influenza pandemic of this century was declared in April of
      2009, with the emergence of a novel H1N1 IAV strain (H1N1pdm) in Mexico and USA.
      Understanding the extent and causes of biases in codon usage is essential to the
      understanding of viral evolution. A comprehensive study to investigate the effect
      of selection pressure imposed by the human host on the codon usage of an
      emerging, pandemic IAV strain and the trends in viral codon usage involved over
      the pandemic time period is much needed. RESULTS: We performed a comprehensive
      codon usage analysis of 310 IAV strains from the pandemic of 2009. Highly biased
      codon usage for Ala, Arg, Pro, Thr and Ser were found. Codon usage is strongly
      influenced by underlying biases in base composition. When correspondence analysis
      (COA) on relative synonymous codon usage (RSCU) is applied, the distribution of
      IAV ORFs in the plane defined by the first two major dimensional factors showed
      that different strains are located at different places, suggesting that IAV codon
      usage also reflects an evolutionary process. CONCLUSIONS: A general association
      between codon usage bias, base composition and poor adaptation of the virus to
      the respective host tRNA pool, suggests that mutational pressure is the main
      force shaping H1N1 pdm IAV codon usage. A dynamic process is observed in the
      variation of codon usage of the strains enrolled in these studies. These results
      suggest a balance of mutational bias and natural selection, which allow the virus
      to explore and re-adapt its codon usage to different environments. Recoding of
      IAV taking into account codon bias, base composition and adaptation to host tRNA
      may provide important clues to develop new and appropriate vaccines.

PMID- 23134596
TI  - Effective normalization for copy number variation detection from whole genome
      sequencing.
AB  - BACKGROUND: Whole genome sequencing enables a high resolution view of the human
      genome and provides unique insights into genome structure at an unprecedented
      scale. There have been a number of tools to infer copy number variation in the
      genome. These tools, while validated, also include a number of parameters that
      are configurable to genome data being analyzed. These algorithms allow for
      normalization to account for individual and population-specific effects on
      individual genome CNV estimates but the impact of these changes on the estimated
      CNVs is not well characterized. We evaluate in detail the effect of normalization
      methodologies in two CNV algorithms FREEC and CNV-seq using whole genome
      sequencing data from 8 individuals spanning four populations. METHODS: We apply
      FREEC and CNV-seq to a sequencing data set consisting of 8 genomes. We use
      multiple configurations corresponding to different read-count normalization
      methodologies in FREEC, and statistically characterize the concordance of the CNV
      calls between FREEC configurations and the analogous output from CNV-seq. The
      normalization methodologies evaluated in FREEC are: GC content, mappability and
      control genome. We further stratify the concordance analysis within genic, non
      genic, and a collection of validated variant regions. RESULTS: The GC content
      normalization methodology generates the highest number of altered copy number
      regions. Both mappability and control genome normalization reduce the total
      number and length of copy number regions. Mappability normalization yields
      Jaccard indices in the 0.07 - 0.3 range, whereas using a control genome
      normalization yields Jaccard index values around 0.4 with normalization based on
      GC content. The most critical impact of using mappability as a normalization
      factor is substantial reduction of deletion CNV calls. The output of another
      method based on control genome normalization, CNV-seq, resulted in comparable CNV
      call profiles, and substantial agreement in variable gene and CNV region calls.
      CONCLUSIONS: Choice of read-count normalization methodology has a substantial
      effect on CNV calls and the use of genomic mappability or an appropriately chosen
      control genome can optimize the output of CNV analysis.

PMID- 23134597
TI  - Clinical review: The liver in sepsis.
AB  - During sepsis, the liver plays a key role. It is implicated in the host response,
      participating in the clearance of the infectious agents/products. Sepsis also
      induces liver damage through hemodynamic alterations or through direct or
      indirect assault on the hepatocytes or through both. Accordingly, liver
      dysfunction induced by sepsis is recognized as one of the components that
      contribute to the severity of the disease. Nevertheless, the incidence of liver
      dysfunction remains imprecise, probably because current diagnostic tools are
      lacking, notably those that can detect the early liver insult. In this review, we
      discuss the epidemiology, diagnostic tools, and impact on outcome as well as the
      pathophysiological aspects, including the cellular events and clinical picture
      leading to liver dysfunction. Finally, therapeutic considerations with regard to
      the weakness of the pertinent specific approach are examined. 

PMID- 23134598
TI  - Long-term outcomes of a new model of anatomical hydroxyapatite-coated hip
      prosthesis.
AB  - This prospective study was designed to evaluate 196 Anatomique Benoist Giraud
      (ABG II) total hip arthroplasties which were implanted between September 1999 and
      December 2000. A minimum 11 years follow up was completed in 183 cases. The
      bearing surfaces were polyethylene-zirconia in 84 cases, polyethylene-metal in 42
      and ceramic-ceramic in 57. Changes in the femoral stem design, in relation to the
      previous ABG I model, have led to a significant improvement in stress-shielding.
      Polyethylene wear rate was lower by more than 50% compared with non-crosslinked
      polyethylene. Excellent and good results were obtained in 90.32% of cases, and
      implant survival was 98.39% at the end of follow-up. 

PMID- 23134599
TI  - Early postnatal lead exposure induces tau phosphorylation in the brain of young
      rats.
AB  - Cognitive impairment is a common feature of both lead exposure and
      hyperphosphorylation of tau. We, therefore, investigated whether lead exposure
      would induce tau hyperphosphorylation. Wistar rat pups were exposed to 0.2% lead
      acetate via their dams' drinking water from postnatal day 1 to 21. Lead in blood
      and brain were measured by atomic absorption spectrophotometry and the expression
      of tau, phosphorylated tau and various serine/threonine protein phosphatases
      (PP1, PP2A, PP2B and PP5) in the brain was analyzed by Western blot. Lead
      exposure significantly impaired learning and resulted in a significant reduction
      in the expression of tau but increased the phosphorylation of tau at Ser199/202,
      Thr212/Ser214 and Thr231. PP2A expression decreased, whereas, PP1 and PP5
      expression increased in lead-exposed rats. These results demonstrate that early
      postnatal exposure to lead decrease PP2A expression and induce tau
      hyperphosphorylation at several serine and threonine residues.
      Hyperphosphorylation of tau may be a mechanism of Pb-induced deficits in learning
      and memory.

PMID- 23134600
TI  - Repeated simultaneous cortical electrophysiological and behavioral recording in
      rats exposed to manganese-containing nanoparticles.
AB  - Male Wistar rats wearing chronically implanted cortical electrodes were exposed
      to Mn-containing nanoparticles via the airways for 8 weeks following a 2-week pre
      exposure period. The rats' cortical electrical activity and open field motility
      was recorded simultaneously, in weekly repetitions. It was supposed that this
      technique can provide better insight in the development of Mn-induced CNS damage.
      Decreased motility (less distance covered, longer periods of immobility) and
      increased total power of cortical electrical activity developed in parallel in
      the first 4-5 weeks of treatment but showed little change afterwards. Both the
      behavioral and the electrophysiological effect were in fair correlation with the
      rats' internal Mn exposure determined from brain samples. The results confirmed
      the non-linear dose- and time-dependence of Mn effects suggested by previous
      studies. Repeated simultaneous behavioral and electrophysiological recording
      during a longer treatment with neurotoxic metals (or other xenobiotics) seems to
      be a promising method.

PMID- 23134601
TI  - Whole body static magnetic field exposure increases thermal nociceptive threshold
      in the snail, Helix pomatia.
AB  - We investigated the effect of homogeneous and inhomogeneous static magnetic field
      (SMF) exposure on the thermal nociceptive threshold of snail in the hot plate
      test (43  degrees C). Both homogeneous (hSMF) and inhomogeneous (iSMF) SMF
      increased the thermo-nociceptive threshold: 40.2%, 29.2%, or 41.7% after an
      exposure of 20, 30, or 40 min hSMF by p < 0.001, p < 0.0001, or p < 0.001, and
      32.7% or 46.2% after an exposure of 20 or 40 min iSMF by p < 0.05 or p < 0.0001.
      These results suggest that SMF has an antinociceptive effect in snail. On the
      other hand, naloxone as an atypical opioid antagonist in an amount of 1 MUg/g was
      found to significantly decrease the thermo-nociceptive threshold (41.9% by p <
      0.002), which could be antagonized by hSMF exposure implying that hSMF exerts its
      antinociceptive effect partly via opioid receptors.

PMID- 23134602
TI  - Different gene transfer methods at the very early, early, late and whole
      embryonic stages in chicken.
AB  - New technologies in gene transfer combined with experimental embryology make the
      chicken embryo an excellent model system for gene function studies. The
      techniques of in ovo electroporation, in vitro culture for ex ovo electroporation
      and retrovirus-mediated gene transfer have already been fully developed in
      chicken. Yet to our knowledge, there are no definite descriptions on the features
      and application scopes of these techniques. The survival rates of different in
      vitro culture methods were compared and the EGFP expression areas of different
      gene transfer techniques were explored. It was that the optimal timings of
      removing embryo for EC culture and Petri dish system was at E1.5 and E2.5,
      respectively; and optimal timing of injecting retrovirus is at E0. Results
      indicated that the EC culture, in ovo electroporation, the Petri dish system and
      retrovirus-mediated method are, respectively, suitable for the very early, early,
      late and whole embryonic stages in chicken. Comparison of different gene transfer
      methods and establishment of optimal timings are expected to provide a better
      choice of the efficient method for a particular experiment.

PMID- 23134603
TI  - Development of chloroplast microsatellite markers for phylogenetic analysis in
      Brassicaceae.
AB  - By employing in silico tools, we devised new chloroplast microsatellite primers
      for inferring phylogenetic relationships within Brassicaceae. Microsatellite
      repeats were scanned in 12 chloroplast genomes of Brassicaceae, regions flanking
      these repeats were aligned and 19 universal primers were designed. Fifteen of
      these primer pairs are predicted to yield polymorphic amplicons, that are more or
      less evenly distributed throughout the chloroplast genomes. Finally, using PCR,
      we have validated three primer pairs on a limited 'test set' of plants, different
      from those used in computational analysis.

PMID- 23134604
TI  - Assessment of the potentiality of TDZ on multiple shoot induction in Bauhinia
      tomentosa L., a woody legume.
AB  - An efficient and reproducible protocol for in vitro multiplication of Bauhinia
      tomentosa L. was developed. Multiple shoots were regenerated from cotyledonary
      node and stem nodal segments excised from in vitro raised seedlings on Murashige
      and Skoog (MS) medium supplemented with different concentrations (0.1, 0.3, 0.5,
      0.8 and 1.0 MUM) of thidiazuron (TDZ). The maximum response (62.6%) was recorded
      on MS medium amended with 0.8 MUM TDZ. A long exposure to TDZ for 8 weeks showed
      abnormalities such as fasciation and compact shoots formation. To avoid adverse
      effects of prolonged exposure to TDZ in long-term establishment, the culture were
      transferred to TDZ free MS medium for further multiplication and elongation. The
      highest number of shoots and shoot length were recorded at the end of fourth
      subculture passage. Ex vitro rooting was achieved when the basal cut end of
      regenerated shoots were dipped in 200 MUM indole-3-butyric acid (IBA) for half an
      hour followed by their transplantation in plastic pots filled with sterile
      SoilriteTM where 60% plantlets grew well and all expressed normal development.

PMID- 23134605
TI  - DNA content alterations in Tetrahymena pyriformis macronucleus after exposure to
      food preservatives sodium nitrate and sodium benzoate.
AB  - The toxicity, in terms of changes in the DNA content, of two food preservatives,
      sodium nitrate and sodium benzoate was studied on the protozoan Tetrahymena
      pyriformis using DNA image analysis technology. For this purpose, selected doses
      of both food additives were administered for 2 h to protozoa cultures and DNA
      image analysis of T. pyriformis nuclei was performed. The analysis was based on
      the measurement of the Mean Optical Density which represents the cellular DNA
      content. The results have shown that after exposure of the protozoan cultures to
      doses equivalent to ADI, a statistically significant increase in the macronuclear
      DNA content compared to the unexposed control samples was observed. The observed
      increase in the macronuclear DNA content is indicative of the stimulation of the
      mitotic process and the observed increase in MOD, accompanied by a stimulation of
      the protozoan proliferation activity is in consistence with this assumption.
      Since alterations at the DNA level such as DNA content and uncontrolled mitogenic
      stimulation have been linked with chemical carcinogenesis, the results of the
      present study add information on the toxicogenomic profile of the selected
      chemicals and may potentially lead to reconsideration of the excessive use of
      nitrates aiming to protect public health.

PMID- 23134606
TI  - In vitro interactions of amantadine hydrochloride, R-(-)-deprenyl hydrochloride
      and valproic acid sodium salt with antifungal agents against filamentous fungal
      species causing central nervous system infection.
AB  - The mortality rates of fungal infections that affect the central nervous system
      are high in consequence of the absence of effective antifungal drugs with good
      penetration across the blood-brain barrier and the blood-cerebrospinal fluid
      barrier. In the present work in vitro antifungal activities of three good
      penetrating non-antifungal drugs (amantadine hydrochloride, R-(-)-deprenyl
      hydrochloride, valproic acid sodium salt) and their combinations with three
      antifungal agents (amphotericin B, itraconazole, terbinafine) were tested with
      broth microdilution method against eight fungal isolates belonging to Zygomycetes
      (Lichtheimia corymbifera, Rhizomucor miehei, Rhizopus microsporus var.
      rhizopodiformis, Saksenaeavasiformis) and Aspergillus genus (A. flavus, A.
      fumigatus, A. nidulans, A. terreus). These are known to be possible agents of
      central nervous fungal infections (CNFI). When used alone, the investigated
      nonantifungal drugs exerted slight antifungal effects. In their combinations with
      antifungal agents they acted antagonistically, additively and synergistically
      against zygomyceteous isolates. Primarily antagonistic interactions were revealed
      between the investigated drugs in case of Aspergilli, but additive and
      synergistic interactions were also observed. The additive and synergistic
      combinations allowed the usage of reduced concentrations of antifungal agents to
      inhibit the fungal growth in our study. These combinations would be a basis of an
      effective, less toxic therapy for treatment of CNFI.

PMID- 23134607
TI  - Beyond the red complex and into more complexity: the polymicrobial synergy and
      dysbiosis (PSD) model of periodontal disease etiology.
AB  - Recent advancements in the periodontal research field are consistent with a new
      model of pathogenesis according to which periodontitis is initiated by a
      synergistic and dysbiotic microbial community rather than by select
      'periopathogens', such as the 'red complex'. In this polymicrobial synergy,
      different members or specific gene combinations within the community fulfill
      distinct roles that converge to shape and stabilize a disease-provoking
      microbiota. One of the core requirements for a potentially pathogenic community
      to arise involves the capacity of certain species, termed 'keystone pathogens',
      to modulate the host response in ways that impair immune surveillance and tip the
      balance from homeostasis to dysbiosis. Keystone pathogens also elevate the
      virulence of the entire microbial community through interactive communication
      with accessory pathogens. Other important core functions for pathogenicity
      require the expression of diverse molecules (e.g. appropriate adhesins, cognate
      receptors, proteolytic enzymes and proinflammatory surface structures/ligands),
      which in combination act as community virulence factors to nutritionally sustain
      a heterotypic, compatible and proinflammatory microbial community that elicits a
      non-resolving and tissue-destructive host response. On the basis of the
      fundamental concepts underlying this model of periodontal pathogenesis, that is,
      polymicrobial synergy and dysbiosis, we term it the PSD model.

PMID- 23134608
TI  - VimA-dependent modulation of the secretome in Porphyromonas gingivalis.
AB  - The VimA protein of Porphyromonas gingivalis is a multifunctional protein
      involved in cell surface biogenesis. To further determine if its acetyl coenzyme
      A (acetyl-CoA) transfer and putative sorting functions can affect the secretome,
      its role in peptidoglycan biogenesis and effects on the extracellular proteins of
      P. gingivalis FLL92, a vimA-defective mutant, were evaluated. There were
      structural and compositional differences in the peptidoglycan of P. gingivalis
      FLL92 compared with the wild-type strain. Sixty-eight proteins were present only
      in the extracellular fraction of FLL92. Fifteen proteins present in the
      extracellular fraction of the parent strain were missing in the vimA-defective
      mutant. These proteins had protein sorting characteristics that included a C
      terminal motif with a common consensus Gly-Gly-CTERM pattern and a polar tail
      consisting of aromatic amino acid residues. These observations suggest that the
      VimA protein is likely involved in peptidoglycan synthesis, and corroborates our
      previous report, which suggests a role in protein sorting.

PMID- 23134609
TI  - Induction of apoptosis in oral epithelial cells by Candida albicans.
AB  - During infection, interactions between Candida albicans and oral epithelial cells
      result in oral epithelial cell death. This is clinically manifested by the
      development of oral mucosal ulcerations generally associated with discomfort. In
      vitro studies have shown that C. albicans induces early apoptotic alterations in
      oral epithelial cells; however, these studies have also shown that treatment of
      infected cells with caspase inhibitors does not prevent their death. The reasons
      for these contradictory results are unknown and it is still not clear if C.
      albicans stimulates oral epithelial signaling pathways that promote apoptotic
      cell death. Activation of specific death pathways in response to microbial
      organisms plays an essential role in modulating the pathogenesis of a variety of
      infectious diseases. The aim of this study was to (i) characterize C. albicans
      induced apoptotic morphological alterations in oral epithelial cells, and (ii)
      investigate the activation of apoptotic signaling pathways and expression of
      apoptotic genes during infection. Candida albicans induced early apoptotic
      changes in over 50% of oral epithelial cells. However, only 15% of those showed
      mid-late apoptotic alterations. At the molecular level, C. albicans caused a loss
      of the mitochondrial transmembrane potential and translocation of mitochondrial
      cytochrome c. Caspase-3/9 activities increased only during the first hours of
      infection. Moreover, poly[ADP ribose] polymerase 1 was cleaved into apoptotic and
      necrotic-like fragments. Finally, five anti-apoptotic genes were significantly
      upregulated and two pro-apoptotic genes were downregulated during infection.
      Altogether, these findings indicate that epithelial apoptotic pathways are
      activated in response to C. albicans, but fail to progress and promote apoptotic
      cell death.

PMID- 23134610
TI  - Inhibition of Porphyromonas gingivalis-induced periodontal bone loss by CXCR4
      antagonist treatment.
AB  - Microbial pathogens have evolved mechanisms to proactively manipulate innate
      immunity, thereby improving their fitness in mammalian hosts. We have previously
      shown that Porphyromonas gingivalis exploits CXC-chemokine receptor-4 (CXCR4) to
      instigate a subversive crosstalk with Toll-like receptor 2 that inhibits
      leukocyte killing of this periodontal pathogen. However, whether CXCR4 plays a
      role in periodontal disease pathogenesis has not been previously addressed. Here,
      we hypothesized that CXCR4 is required for P. gingivalis virulence in the
      periodontium and that treatment with AMD3100, a potent CXCR4 antagonist, would
      inhibit P. gingivalis-induced periodontitis. Indeed, mice given AMD3100 via
      osmotic minipumps became resistant to induction of periodontal bone loss
      following oral inoculation with P. gingivalis. AMD3100 appeared to act in an
      antimicrobial manner, because mice treated with AMD3100 were protected against P.
      gingivalis colonization and the associated elevation of the total microbiota
      counts in the periodontal tissue. Moreover, even when administered 2 weeks after
      infection, AMD3100 halted the progression of P. gingivalis-induced periodontal
      bone loss. Therefore, AMD3100 can act in both preventive and therapeutic ways and
      CXCR4 antagonism could be a promising novel approach to treat human
      periodontitis.

PMID- 23134611
TI  - Identification and characterization of novel glycoproteins involved in growth and
      biofilm formation by Porphyromonas gingivalis.
AB  - Porphyromonas gingivalis has been implicated as a major pathogen associated with
      chronic periodontitis. To extend our knowledge of post-translational protein
      glycosylation in P. gingivalis, a proteomic analysis involving two-dimensional
      polyacrylamide gel electrophoresis combined with carbohydrate staining and mass
      spectrometry was performed. Four novel glycoproteins, PGN0743, PGN0876, PGN1513
      and PGN0729, in P. gingivalis ATCC 33277 were identified. These four identified
      glycoproteins possess a range of biochemical activities and cellular
      localization. PGN0743 contains a sequence motif identifying it as a FKBP-type cis
      trans isomerase, which has activity usually associated with chaperone functions.
      PGN0876 and PGN1513 contain tetratricopeptide repeat domains that mediate protein
      protein interactions. PGN0729 encodes the outer membrane protein 41 precursor,
      which was previously identified as Pgm6, and is homologous to the OmpA protein in
      Escherichia coli. Several different types of glycoprotein were identified,
      suggesting that P. gingivalis possesses a general mechanism for protein
      glycosylation. PGN0743-deficient and PGN0876-deficient mutants were constructed
      to examine the role(s) of the two identified glycoproteins. Both mutants showed a
      decreased growth rate under nutrient-limited conditions and reduced biofilm
      formation activity. These results suggest that the novel glycoproteins PGN0743
      and PGN0876 play an important role in the growth and colonization of P.
      gingivalis.

PMID- 23134612
TI  - The fate of Treponema denticola within human gingival epithelial cells.
AB  - Treponema denticola is one of the major pathogens associated with chronic
      periodontitis. Bacterial invasion into gingival tissues is a critical process in
      the pathogenesis of periodontal disease. We recently reported that T. denticola
      can invade gingival epithelial cells. The aim of this study is to determine the
      fate of internalized T. denticola in gingival epithelial cells. Immortalized
      human gingival epithelial HOK-16B cells were infected with 5- (and 6-) carboxy
      fluorescein diacetate succinimidyl ester (CFSE)-labeled live or heat-killed T.
      denticola for 24 h, and the presence of bacteria inside the cells was confirmed
      by confocal microscopy. Live T. denticola, but not heat-killed bacteria, invaded
      HOK-16B cells. Confocal microscopy also revealed that internalized T. denticola
      rarely colocalized with either endosomes or lysosomes. Transmission electron
      microscopy of infected cells showed that intracellular T. denticola was localized
      inside endosome-like structures. Although a culture-based antibiotics protection
      assay could not detect viable intracellular T. denticola 12 h after infection, a
      substantial number of bacteria were observed by confocal microscopy and weak
      expression of bacterial 16S ribosomal RNA was detected 48 h after infection. In
      addition, flow cytometric analysis of HOK-16B cells infected with CFSE-labeled T.
      denticola showed no loss of fluorescence over 48 h. Collectively, T. denticola
      invades gingival epithelial cells and remains within the host cells for many
      hours by resisting endolysosomal degradation. These findings may provide new
      insight into the role of T. denticola in the pathogenesis of periodontitis.

PMID- 23134613
TI  - Divergence of the systemic immune response following oral infection with distinct
      strains of Porphyromonas gingivalis.
AB  - Periodontitis is a polymicrobial oral infection characterized by the destruction
      of tooth-supporting structures that can be linked to systemic diseases such as
      cardiovascular disease, diabetes or rheumatoid arthritis. Porphyromonas
      gingivalis, a bacterium implicated in the etiology of periodontitis, has shown
      variation in inducing T-cell responses among different strains. Therefore, in
      this study we investigated the strain-specific immune response using a murine
      experimental model of periodontitis. Periodontitis was induced by P. gingivalis
      strains A7A1-28, W83 and W50, and later confirmed by the presence of P.
      gingivalis in the oral microflora and by alveolar bone resorption. Splenocytes
      were evaluated for gene expression, cellular proteins and cytokine expression.
      Dendritic cells were stimulated in vitro for T helper cell-cytokine profiling.
      Results showed that P. gingivalis had the ability to alter the systemic immune
      response after bacterial exposure. Strains W50 and W83 were shown to induce
      alveolar bone loss, whereas the A7A1-28 strain did not significantly promote bone
      resorption in mice. Splenocytes derived from mice infected with strains W50 and
      W83 induced expression of high levels of interleukin-4 (IL-4) but A7A1-28
      stimulated increased IL-10. Stimulation of dendritic cells in vitro showed a
      similar pattern of cytokine expression of IL-12p40, IL-6 and transforming growth
      factor-beta among strains. A distinct systemic response in vivo was observed
      among different strains of P. gingivalis, with IL-10 associated with the least
      amount of alveolar bone loss. Evaluation of pathogen-driven systemic immune
      responses associated with periodontal disease pathogenesis may assist in defining
      how periodontitis may impact other diseases.

PMID- 23134614
TI  - A diploid wheat TILLING resource for wheat functional genomics.
AB  - BACKGROUND: Triticum monococcum L., an A genome diploid einkorn wheat, was the
      first domesticated crop. As a diploid, it is attractive genetic model for the
      study of gene structure and function of wheat-specific traits. Diploid wheat is
      currently not amenable to reverse genetics approaches such as insertion
      mutagenesis and post-transcriptional gene silencing strategies. However, TILLING
      offers a powerful functional genetics approach for wheat gene analysis. RESULTS:
      We developed a TILLING population of 1,532 M2 families using EMS as a mutagen. A
      total of 67 mutants were obtained for the four genes studied. Waxy gene mutation
      frequencies are known to be 1/17.6 - 34.4 kb DNA in polyploid wheat TILLING
      populations. The T. monococcum diploid wheat TILLING population had a mutation
      frequency of 1/90 kb for the same gene. Lignin biosynthesis pathway genes- COMT1,
      HCT2, and 4CL1 had mutation frequencies of 1/86 kb, 1/92 kb and 1/100 kb,
      respectively. The overall mutation frequency of the diploid wheat TILLING
      population was 1/92 kb. CONCLUSION: The mutation frequency of a diploid wheat
      TILLING population was found to be higher than that reported for other diploid
      grasses. The rate, however, is lower than tetraploid and hexaploid wheat TILLING
      populations because of the higher tolerance of polyploids to mutations. Unlike
      polyploid wheat, most mutants in diploid wheat have a phenotype amenable to
      forward and reverse genetic analysis and establish diploid wheat as an attractive
      model to study gene function in wheat. We estimate that a TILLING population of
      5, 520 will be needed to get a non-sense mutation for every wheat gene of
      interest with 95% probability.

PMID- 23134615
TI  - Electrophilic reactivity of tetrabromorhodamine 123 is bromine induced:
      convergent interpretation through complementary molecular descriptors.
AB  - Nucleophilic addition of water and of methanol to 3,6-diamino-2,4,5,7-tetrabromo
      9-[2-(methoxycarbonyl) phenyl]-9H-xanthen-9-ylium, 4BrR123, yields respectively 2
      (3,6-diamino-2,4,5,7-tetrabromo-9-hydroxy-9H-xanthen-9-yl)xanthyl benzoate,
      HO4BrR123 and 2-(3,6-diamino-2,4,5,7-tetrabromo-9-methoxy-9H-xanthen-9-yl)xanthyl
      benzoate, MeO4BrR123. The novel experimental results are addressed theoretically.
      The linear free energy relationship, LFER, second-order perturbation theory
      analysis of the natural bond orbital, NBO, and quantum theory of atoms in
      molecules, QTAIM, lead to the same conclusion: the electron-withdrawing effect of
      bonded Br atoms in 4BrR123 extremely enhances the molecular electrophilicity, as
      compared to 3,6-diamino-9-[2-(methoxycarbonyl) phenyl]-9H-xanthen-9-ylium, R123.
      The reactivity of these diaminoxanthylium cations is discussed in the context of
      local and global softness in extended conjugated systems.

PMID- 23134616
TI  - AICAR inhibits ceramide biosynthesis in skeletal muscle.
AB  - BACKGROUND: The worldwide prevalence of obesity has lead to increased efforts to
      find therapies to treat obesity-related pathologies. Ceramide is a well
      established mediator of several health problems that arise from adipose tissue
      expansion. The purpose of this study was to determine whether AICAR, an AMPK
      activating drug, selectively reduces skeletal muscle ceramide synthesis. METHODS:
      Murine myotubes and rats were challenged with palmitate and high-fat diet,
      respectively, to induce ceramide accrual, in the absence or presence of AICAR.
      Transcript levels of the rate-limiting enzyme in ceramide biosynthesis, serine
      palmitoyltransferase 2 (SPT2) were measured, in addition to lipid analysis.
      Student's t-test and ANOVA were used to assess the association between outcomes
      and groups. RESULTS: Palmitate alone induced an increase in serine
      palmitoyltransferase 2 (SPT2) expression and an elevation of ceramide levels in
      myotubes. Co-incubation with palmitate and AICAR prevented both effects. However,
      ceramide and SPT2 increased with the addition of compound C, an AMPK inhibitor.
      In rats fed a high-fat diet (HFD), soleus SPT2 expression increased compared with
      normal chow-fed littermates. Moreover, rats on HFD that received daily AICAR
      injections had lower SPT2 levels and reduced muscle ceramide content compared
      with those on HFD only. CONCLUSIONS: These results suggest that AICAR reduces
      ceramide synthesis by targeting SPT2 transcription, likely via AMPK activation as
      AMPK inhibition prevented the AICAR-induced improvements. Given the role of
      skeletal muscle ceramide in insulin resistance, it is tempting to speculate that
      interventions that activate AMPK may lead to long-term ceramide reduction and
      improved metabolic function.

PMID- 23134617
TI  - ATP and luciferase assays to determine the rate of drug action in in vitro
      cultures of Plasmodium falciparum.
AB  - BACKGROUND: Knowledge of the rate of action of compounds against cultured malaria
      parasites is required to determine the optimal time-points for drug mode of
      action studies, as well as to predict likely in vivo parasite clearance rates in
      order to select optimal hit compounds for further development. In this study,
      changes in parasite ATP levels and transgenic luciferase reporter activity were
      explored as means to detect drug-induced stress in cultured parasites. METHODS:
      In vitro cultures of Plasmodium falciparum 3D7 wild-type or firefly luciferase
      expressing parasites were incubated with a panel of six anti-malarial compounds
      for 10 hours and parasite ATP levels or luciferase activity determined at two
      hour intervals using luminescence-based reagents. For comparative purposes,
      parasite morphology changes were evaluated by light microscopy, as well as the
      extent to which parasites recover after 48 hours from a six-hour drug treatment
      using a parasite lactate dehydrogenase assay. RESULTS: Changes in parasite ATP
      levels displayed three phenotypes: mild or no change (chloroquine, DFMO); 2-4
      fold increase (mefloquine, artemisinin); severe depletion (ritonavir,
      gramicidin). The respective phenotypes and the rate at which they manifested
      correlated closely with the extent to which parasites recovered from a six-hour
      drug treatment (with the exception of chloroquine) and the appearance and
      severity of morphological changes observed by light microscopy. Luciferase
      activity decreased profoundly in parasites treated with mefloquine, artemisinin
      and ritonavir (34-67% decrease in 2 hours), while chloroquine and DFMO produced
      only mild changes over 10 hours. Gramicidin yielded intermediate decreases in
      luciferase activity. CONCLUSIONS: ATP levels and luciferase activity respond
      rapidly to incubation with anti-malarial drugs and provide quantitative read-outs
      to detect the appearance and magnitude of drug-induced stress in cultured
      parasites. The correlation between the observed changes and irreversible parasite
      toxicity is not yet sufficiently clear to predict clinical clearance rates, but
      may be useful for ranking compounds against each other and standard drugs vis-a
      vis rate of action and for determining early time-points for drug mode of action
      studies.

PMID- 23134618
TI  - C2Maps: a network pharmacology database with comprehensive disease-gene-drug
      connectivity relationships.
AB  - BACKGROUND: Network pharmacology has emerged as a new topic of study in recent
      years. It aims to study the myriad relationships among proteins, drugs, and
      disease phenotypes. The concept of molecular connectivity maps has been proposed
      to establish comprehensive knowledge links between molecules of interest in a
      given biological context. Molecular connectivity maps between drugs and
      genes/proteins in specific disease contexts can be particularly valuable, since
      the functional approach with these maps helps researchers gain global
      perspectives on both the therapeutic profiles and toxicological profiles of
      candidate drugs. METHODS: To assess drug pharmacological effect, we assume that
      "ideal" drugs for a patient can treat or prevent the disease by modulating gene
      expression profiles of this patient to the similar level with those in healthy
      people. Starting from this hypothesis, we build comprehensive disease-gene-drug
      connectivity relationships with drug-protein directionality (inhibit/activate)
      information based on a computational connectivity maps (C2Maps) platform. An
      interactive interface for directionality annotation of drug-protein pairs with
      literature evidences from PubMed has been added to the new version of C2Maps. We
      also upload the curated directionality information of drug-protein pairs specific
      for three complex diseases - breast cancer, colorectal cancer and Alzheimer
      disease. RESULTS: For relevant drug-protein pairs with directionality
      information, we use breast cancer as a case study to demonstrate the
      functionality of disease-specific searching. Based on the results obtained from
      searching, we perform pharmacological effect evaluation for two important breast
      cancer drugs on treating patients diagnosed with different breast cancer
      subtypes. The evaluation is performed on a well-studied breast cancer gene
      expression microarray dataset to portray how useful the updated C2Maps is in
      assessing drug efficacy and toxicity information. CONCLUSIONS: The C2Maps
      platform is an online bioinformatics resource that provides biologists with
      directional relationships between drugs and genes/proteins in specific disease
      contexts based on network mining, literature mining, and drug effect annotating.
      A new insight to assess overall drug efficacy and toxicity can be provided by
      using the C2Maps platform to identify disease relevant proteins and drugs. The
      case study on breast cancer correlates very well with the existing pharmacology
      of the two breast cancer drugs and highlights the significance of C2Maps
      database.

PMID- 23134619
TI  - Hyperactivity persists in male and female adults with ADHD and remains a highly
      discriminative feature of the disorder: a case-control study.
AB  - BACKGROUND: Symptoms of hyperactivity are believed to fade with age leaving ADHD
      adults mostly inattentive and impulsive. Our aim was to test this assertion using
      objective measures of hyperactivity, impulsivity and inattention. METHOD:
      Participants were 40 subjects with ADHD (23M/17F; 35+/-10 yrs) and 60 healthy
      adults (28M/32F; 29+/-9 yrs) blindly assessed using Wender-Reimherr interview
      ratings, Structured Clinical Interview for DSM-IV Disorders and DSM-IV criteria.
      Infrared motion capture systems tracked head and leg movements during performance
      of a No-4's cognitive control task. Subjects also completed the Conners' CPT-II.
      RESULTS: ADHD and controls differed significantly in activity and attention.
      Effect sizes for activity measures (d' = 0.7-1.6) were, on average, two-fold
      larger than differences in attention or impulsivity, correlated more strongly
      with executive function ratings and were more discriminatory (ROC area = 0.83 for
      activity composite, 0.65 for No-4's distraction composite, 0.63 for Conners' CPT
      II confidence index, 0.96 for the combined activity and attention diagnostic
      index). This finding was true for subjects with the predominantly inattentive
      subtype as well as subjects with combined or predominantly hyperactive/impulsive
      subtype. Males and females with ADHD were equally active. The superior accuracy
      of activity measures was confirmed using Random Forest and predictive modeling
      techniques. CONCLUSIONS: Objectively measured hyperactivity persists in adults
      with ADHD and is a more discriminative feature of the disorder than computerized
      measures of inattention or impulsivity. This finding supports the hypothesis that
      a deficient ability to sit still remains a defining feature of the disorder in
      adults when it is measured objectively.

PMID- 23134621
TI  - Characterisation of dissolved organic compounds in hydrothermal fluids by stir
      bar sorptive extraction - gas chomatography - mass spectrometry. Case study: the
      Rainbow field (36 degrees N, Mid-Atlantic Ridge).
AB  - The analysis of the dissolved organic fraction of hydrothermal fluids has been
      considered a real challenge due to sampling difficulties, complexity of the
      matrix, numerous interferences and the assumed ppb concentration levels. The
      present study shows, in a qualitative approach, that Stir Bar Sorptive Extraction
      (SBSE) followed by Thermal Desorption - Gas Chromatography - Mass Spectrometry
      (TD-GC-MS) is suitable for extraction of small sample volumes and detection of a
      wide range of volatile and semivolatile organic compounds dissolved in
      hydrothermal fluids. In a case study, the technique was successfully applied to
      fluids from the Rainbow ultramafic-hosted hydrothermal field located at 36
      degrees 14'N on the Mid-Atlantic Ridge (MAR). We show that n-alkanes, mono- and
      poly- aromatic hydrocarbons as well as fatty acids can be easily identified and
      their retention times determined. Our results demonstrate the excellent
      repeatability of the method as well as the possibility of storing stir bars for
      at least three years without significant changes in the composition of the
      recovered organic matter. A preliminary comparative investigation of the organic
      composition of the Rainbow fluids showed the great potential of the method to be
      used for assessing intrafield variations and carrying out time series studies.
      All together our results demonstrate that SBSE-TD-GC-MS analyses of hydrothermal
      fluids will make important contributions to the understanding of geochemical
      processes, geomicrobiological interactions and formation of mineral deposits.

PMID- 23134622
TI  - A comparison of E15.5 fetus and newborn rat serum proteomes.
AB  - BACKGROUND: Serum proteins carry out several functions in the circulation,
      including transfer, immunological functions, messenger functions, coagulation,
      and regulation of homeostasis. To investigate changes in serum proteins that
      occur during development, the serum proteomes of embryonic 15.5 (E15.5) fetuses
      and newborn rats were compared using LC-MS/MS. RESULTS: A total of 958 proteins
      were identified in the serum of rats at both developmental stages. The serum
      proteome pattern of newborn rats was compared to E15.5 fetuses by relative
      quantitation. The expression patterns of hemoglobin subunits were different at
      the two stages, with most of the subunits having decreased expression in newborn
      rats compared to E15.5 fetuses. In addition, 8 of 12 apolipoproteins were
      significantly decreased and 10 of 11 identified complement molecules were
      increased, with 4 exhibiting a significant increase. Moreover, 11 of 14 of the
      significantly increased enzyme regulators were inhibitors. The serum proteome
      patterns of different littermates from both developmental stages were also
      compared. We found that the levels of many highly abundant serum proteins varied
      between littermates, and the variations were larger than the variations of the
      technical control. CONCLUSIONS: The serum proteomes of newborn rats and E15.5
      fetuses were compared. The expression patterns of hemoglobin subunits were
      different at the two developmental stages, with most of the subunits having
      decreased expression. The majority of apolipoproteins had significantly decreased
      expression, while almost all identified complement proteins had increased
      expression. The levels of several highly abundant serum proteins also varied
      among littermates at these two developmental stages. This is the first study
      using LC-MS/MS to investigate serum proteome development.

PMID- 23134623
TI  - Performing magnetic resonance imaging in patients with implantable pacemakers and
      defibrillators: results of a European Heart Rhythm Association survey.
AB  - The purpose of our survey was to evaluate the experience, current practice and
      attitudes of performing magnetic resonance imaging (MRI) studies in patients with
      cardiac implantable electronic devices. Fifty-one centre-members of European
      Heart Rhythm Association Research network have responded to the survey. According
      to the obtained data, 55.2% of responding centres do not perform MRI scans in
      patients with non-MRI-certified pacemakers and 65.8% in patients with such
      implantable cardioverter defibrillators (ICDs). Reported complication rate in
      patients with non-MRI-certified devices is low and conforms to the literature
      data. Experience with newer MRI-compatible pacemakers and ICDs is limited to
      single cases in most centres. This survey shows limited experience with
      performing MRI studies in patients with implanted pacemakers and ICDs. In
      concordance with available guidelines, most centres limit MRI scans in patients
      with non-MRI-certified devices. The implant numbers for MRI-certified devices and
      experience with performing MRI scans in these patients are still low.

PMID- 23134625
TI  - Increase in standard cholesterol and large HDL particle subclasses in
      antiretroviral-naive patients prescribed efavirenz compared to
      atazanavir/ritonavir.
AB  - BACKGROUND: Cardiovascular risk in HIV-infected patients is related, at least in
      part, to serum lipid alterations before and after HAART. Lipoprotein-particle
      subclasses may also have an effect, but comparative data after standard HAART
      regimens are limited. METHODS: This was a substudy of a trial in 91
      antiretroviral-naive patients randomized to tenofovir + emtricitabine +
      atazanavir/ritonavir (ATV/r) or efavirenz (EFV). Over-time trends from baseline
      to week 48 in total cholesterol (TC), triglycerides (TG), low-density lipoprotein
      cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), HDL particles
      (HDLp), and TC:HDL-C and TG:HDL-C ratios were analyzed by analysis of covariance
      (ANCOVA). Furthermore, confidence intervals for differences between the 2 groups
      at week 48 were calculated. Indications for lipid-lowering interventions and low
      HDL-C were also studied. RESULTS: ANCOVA showed that, with respect to patients
      receiving ATV/r, those prescribed efavirenz (EFV) had greater increases reported
      as mean differences in lipid values at week 48: 14 mg/dL (95% CI, 0.2 to 27) for
      TC, 14 mg/dL (95% CI, 4 to 25) for LDL-C, 5 mg/dL (95% CI, 2 to 9) for HDL-C, and
      2.2 mg/dL (95% CI, 0.4 to 4) for large HDLp. Proportions of subjects with
      indications for lipid-lowering interventions and with HDL-C <40 mg/dL did not
      differ significantly. CONCLUSIONS: Patients prescribed EFV had greater increases
      in TC, LDL-C, and HDL-C. Although no significant differences were detected
      between the 2 groups for the TC:HDL ratio and for indications to start lipid
      lowering interventions, large HDLp increased more in the EFV group compared to
      the ATV/r group, suggesting a protective effect associated with EFV use.

PMID- 23134624
TI  - ARIES 144 week results: durable virologic suppression in HIV-infected patients
      simplified to unboosted atazanavir/abacavir/lamivudine.
AB  - BACKGROUND: The open-label study ARIES (ClinicalTrials.gov NCT00440947) utilized
      a ritonavir (/r)-boosted protease inhibitor treatment simplification strategy.
      Antiretroviral-naive subjects received abacavir/lamivudine (ABC/3TC) +
      atazanavir/ ritonavir (ATV/r) from baseline through randomization at week 36,
      then maintained or discontinued ritonavir for an additional 108 weeks. Non
      inferiority of the unboosted regimen was demonstrated at week 84. In this
      optional extension phase, virologic suppression and adverse events were assessed
      through week 144. METHODS: Patients were randomized at week 36 if they had
      confirmed HIV RNA <50 copies/mL by week 30 and no previous virologic failure (VF;
      defined as failure to achieve HIV RNA <400 copies/mL or confirmed rebound after
      achieving HIV RNA >=400 copies/mL). Three hundred sixty-nine subjects who
      completed 84 weeks in ARIES participated in the extension phase and maintained
      their randomized regimen for an additional 60 weeks post randomization. RESULTS:
      At week 144, 146/189 (77%) versus 132/180 (73%) subjects in the unboosted ATV and
      ATV/r groups, respectively, maintained HIV RNA <50 copies/mL. Post randomization
      (weeks 36-144), treatment-related grade 2-4 adverse events were more common in
      the ATV/r-treated (23%) compared to the ATV-treated (13%) group; the most
      frequently reported was increased serum bilirubin (6% of ATV-treated subjects vs
      14 % of ATV/r-treated subjects). During the extension phase, 3% (11/369) of
      subjects met protocol-defined VF (5 ATV-treated and 6 ATV/ r-treated subjects);
      one ATV/r-treated subject had treatment-emergent major viral resistance
      associated mutations. The median change in fasting triglycerides from baseline to
      week 144 was significantly different (P=.001) in the ATV-treated (-8.5 mg/dL)
      compared to the ATV/r-treated (28.5 mg/dL) groups. CONCLUSIONS: These long-term
      study results demonstrate that ATV in combination with ABC/3TC is a potent, well
      tolerated regimen in patients who have achieved initial suppression on a
      ritonavir-boosted regimen.

PMID- 23134626
TI  - Effect of darunavir on lipid profile in HIV-infected patients.
AB  - Highly active antiretroviral therapy regimens, consisting of a ritonavir-boosted
      protease inhibitor (PI) and 2 nucleoside reverse transcriptase inhibitors, are
      established first-line regimens for HIV-infected patients. However, a common
      adverse effect in patients receiving PIs is dyslipidemia, characterized by
      increases in plasma levels of triglycerides, low-density lipoprotein cholesterol,
      and total cholesterol (TC). These lipid changes, as well as other well-described
      risk factors, may predispose patients to the development of cardiovascular
      disease, an important comorbidity, especially as the lifespan of HIV-infected
      patients has increased dramatically in recent years. Among PIs, ritonavir-boosted
      atazanavir (ATV/r) and, more recently, ritonavir-boosted darunavir (DRV/r) have
      demonstrated potent antiviral efficacy with more favorable lipid profiles than
      other PIs. This review provides an overview of the lipid effects of DRV/r.
      Studies with DRV/r in healthy volunteers and in both treatment-naive and 
      experienced patients have demonstrated that changes in tri-glycerides and TC are
      comparable to those seen with ATV/r.

PMID- 23134627
TI  - Feasibility and reliability of interactive voice response assessment of HIV
      medication adherence: research and clinical implications.
AB  - BACKGROUND: There are well-documented negative consequences of nonadherence to
      HIV medications. Telephone-based interactive voice response (IVR) technologies
      may hold promise for assessing nonadherence in both research and clinical
      contexts; however, little psychometric research has been conducted on this topic.
      OBJECTIVE: In the present pilot study, we test the feasibility and reliability of
      a simplified patient-initiated, daily IVR system with a convenience sample of HIV
      patients attending a university-affiliated infectious disease clinic. METHODS:
      Participants were asked to call in to an IVR system to report adherence daily
      during 2 weeks of a larger prospective study. Response rates and patterns were
      analyzed for feasibility and compared to retrospective, self-report timeline
      follow-back (TLFB) adherence reporting. RESULTS: The IVR protocol showed moderate
      feasibility, with participants reporting adherence behavior on 63.4% of days.
      However, agreement with TLFB data was low, particularly for days in which
      participants reported incomplete adherence. CONCLUSIONS: The IVR protocol tested
      in the current trial shows some promise. Completion rates were higher than in
      previous trials. Future research is needed to further enhance the feasibility of
      IVR for HIV medication adherence and to compare responses to more objective
      measures on HIV adherence.

PMID- 23134628
TI  - Vitamin D deficiency is common among HIV-infected breastfeeding mothers in Pune,
      India, but is not associated with mother-to-child HIV transmission.
AB  - A recent report from Tanzania demonstrated an increased risk of being HIV
      infected or of dying at birth among children born to breastfeeding mothers with
      low baseline vitamin D levels. We conducted a nested case-control study among HIV
      infected pregnant women in western India to confirm the association between
      maternal vitamin D levels and mother-to-child transmission (MTCT) of HIV. Vitamin
      D insufficiency and deficiency were common among HIV-infected pregnant women, but
      were not associated with mother to child HIV transmission at 1 year postpartum
      (adjusted odds ratio [AOR], 0.66; 95% CI, 0.30-1.45; P = .30).

PMID- 23134629
TI  - Switch from etravirine twice daily to once daily in non-nucleoside reverse
      transcriptase inhibitor (NNRTI)-resistant HIV-infected patients with suppressed
      viremia: the Monetra study.
AB  - BACKGROUND: Etravirine (ETR) is recommended as twice-daily dosing in pretreated
      patients. There are no data regarding the use of ETR once daily in HIV
      experienced patients with prior resistance to first-generation non-nucleoside
      reverse transcripase inhibitors (NNRTIs). OBJECTIVES: To evaluate the capacity of
      once-daily ETR to maintain suppressed viremia over 48 weeks after switching from
      ETR twice daily in NNRTI-experienced patients. METHODS: In this pilot open-label
      study, patients with plasma viral load (pVL) <50 copies/mL on a stable ETR 200 mg
      bid regimen were enrolled to switch to ETR 400 mg qd and followed up over 48
      weeks. The primary endpoint was the proportion of patients with pVL <50 copies/mL
      at week 24. Secondary endpoints included the rate of pVL< 50 copies/mL at week
      48, ETR pharmacokinetic parameters, and tolerability and resistance profile.
      RESULTS: Twenty-four patients were included. They had extensive antiretroviral
      treatment for a median of 14 years (range, 1-19). All except for 2 had prior
      resistance to NNRTIs. Seven patients discontinued ETR once daily prior to week 48
      for virological failure (3), protocol deviation (3), and side effects (1). At
      week 24, 95% of patients maintained pVL< 50 copies/mL (95% CI, 78.4-99.7) and 85%
      at week 48 (95%CI, 65.6-95.8). Two of the 3 patients with virological failure had
      ETR resistance mutations prior to initiation. The median ETR C(trough) level
      remained stable after switching from twice daily 515 ng/mL (340-758) to once
      daily 422 ng/mL (264-655). CONCLUSION: These results suggest that ETR is
      effective as a once-daily regimen in patients with prior NNRTI experience when
      HIV is sensitive to ETR. The stability of C(trough) concentrations on a once
      daily regimen confirms the once-daily profile of the drug in experienced
      patients.

PMID- 23134630
TI  - Missing scheduled visits in the outpatient clinic as a marker of short-term
      admissions and death.
AB  - INTRODUCTION: It is not uncommon for patients with HIV infection to miss
      scheduled visits in outpatient clinics without justifying the failure to appear
      or reschedule the appointment. Few studies have assessed the impact of
      inconsistent follow-ups on resource use and disease outcomes in this patient
      population. OBJECTIVE: To assess the effect of missing scheduled visits to the
      outpatient clinic on the health outcomes of HIV-infected patients. METHODS:
      Between January and June 2006, we conducted a prospective observational study
      monitoring assistance at an outpatient HIV/AIDS clinic of a tertiary hospital
      within a public health care system in a developed country. The short-term
      subsequent events (deaths and admissions) of the population were observed from
      January to December 2006. RESULTS: Of the 1,733 HIV patients who were scheduled
      in the outpatient clinic, 103 met the criteria of missing scheduled visit (5.9%).
      Hospital admissions and mortality rates were significantly higher in the missing
      scheduled visit group compared to non-missing scheduled visits (27.2% vs 8.9%; P
      < .001 and 5.8% vs 0.7%; P < .001, respectively). Patients with missing scheduled
      visits had a higher risk of hospital admissions (odds ratio [OR] 2.4; 95% CI, 1.4
      4) and mortality (OR 6.7; 95% CI, 2.2-18.5) adjusted by age, CD4 cell count, HIV
      stage, and category of transmission. CONCLUSIONS: Missing scheduled visits was an
      independent predicting factor for hospital admission and mortality. It is
      warranted to monitor and implement resources to reduce missed appointments.

PMID- 23134631
TI  - Comments to Garvey et al.: "Low rates of neurocognitive impairment are observed
      in neuro-asymptomatic HIV-infected subjects on effective antiretroviral therapy".

PMID- 23134633
TI  - Determination of the full-genome sequence of hepatitis E virus (HEV) SAAS-FX17
      and use as a reference to identify putative HEV genotype 4 virulence
      determinants.
AB  - BACKGROUND: Four major genotypes of hepatitis E virus (HEV), the causative agent
      of hepatitis E, have so far been recognized. While genotypes 3 and 4 are both
      zoonotic, the disease symptoms caused by the latter tend to be more severe. To
      examine if specific nucleotide/amino acid variations between genotypes 3 and 4
      play a role in determining the severity of hepatitis E disease, the complete
      genome of one swine HEV genotype 4 isolate, SAAS-FX17, was determined and
      compared with other genotype 4 and genotype 3 genomes to identify putative HEV
      genotype 4 virulence determinants. RESULTS: A total of 42 conformable nt/aa
      variations between genotype 3 and 4 HEVs were detected, of which 19 were proposed
      to be potential disease severity determinants for genotype 4 strains.
      CONCLUSIONS: One potential determinant was located in each of the 5'-UTR and 3'
      UTR, 3 and 12 within ORF1 and ORF2 respectively, and 2 in the junction region.

PMID- 23134634
TI  - Major incident preparedness and on-site work among Norwegian rescue personnel - a
      cross-sectional study.
AB  - BACKGROUND: A major incident has occurred when the number of live casualties,
      severity, type of incident or location requires extraordinary resources. Major
      incident management is interdisciplinary and involves triage, treatment and
      transport of patients. We aimed to investigate experiences within major incident
      preparedness and management among Norwegian rescue workers. METHODS: A
      questionnaire was answered by 918 rescue workers across Norway. Questions rated
      from 1 (doesn't work) to 7 (works excellently) are presented as median and range.
      RESULTS: Health-care personnel constituted 34.1% of the participants,
      firefighters 54.1% and police 11.8%. Training for major incident response scored
      5 (1, 7) among health-care workers and 4 (1, 7) among firefighters and police.
      Preparedness for major incident response scored 5 (1, 7) for all professions.
      Interdisciplinary cooperation scored 5 (3, 7) among health-care workers and
      police and 5 (1, 7) among firefighters. Among health-care workers, 77.5% answered
      that a system for major-incident triage exists; 56.3% had triage equipment
      available. The majority - 45.1% of health-care workers, 44.7% of firefighters and
      60.4% of police - did not know how long it would take to get emergency stretchers
      to the scene. CONCLUSIONS: Rescue personnel find major incident preparedness and
      on-scene multidisciplinary cooperation to function well. Some shortcomings are
      reported with regard to systems for major incident triage, tagging equipment for
      triage and knowledge about access to emergency stretchers.

PMID- 23134635
TI  - Pyroelectric nanogenerators for driving wireless sensors.
AB  - We demonstrate a pyroelectric nanogenerator (PENG) based on a lead zirconate
      titanate (PZT) film, which has a pyroelectric coefficient of about -80 nC/cm(2)K.
      For a temperature change of 45 K at a rate of 0.2 K/s, the output open-circuit
      voltage and short-circuit current density of the PENG reached 22 V and 171
      nA/cm(2), respectively, corresponding to a maximum power density of 0.215
      mW/cm(3). A detailed theory was developed for understanding the high output
      voltage of PENG. A single electrical output pulse can directly drive a liquid
      crystal display (LCD) for longer than 60 s. A Li-ion battery was charged by the
      PENG at different working frequencies, which was used to drive a green light
      emitting diode (LED). The demonstrated PENG shows potential applications in
      wireless sensors.

PMID- 23134636
TI  - Pathway Distiller - multisource biological pathway consolidation.
AB  - BACKGROUND: One method to understand and evaluate an experiment that produces a
      large set of genes, such as a gene expression microarray analysis, is to identify
      overrepresentation or enrichment for biological pathways. Because pathways are
      able to functionally describe the set of genes, much effort has been made to
      collect curated biological pathways into publicly accessible databases. When
      combining disparate databases, highly related or redundant pathways exist, making
      their consolidation into pathway concepts essential. This will facilitate
      unbiased, comprehensive yet streamlined analysis of experiments that result in
      large gene sets. METHODS: After gene set enrichment finds representative pathways
      for large gene sets, pathways are consolidated into representative pathway
      concepts. Three complementary, but different methods of pathway consolidation are
      explored. Enrichment Consolidation combines the set of the pathways enriched for
      the signature gene list through iterative combining of enriched pathways with
      other pathways with similar signature gene sets; Weighted Consolidation utilizes
      a Protein-Protein Interaction network based gene-weighting approach that finds
      clusters of both enriched and non-enriched pathways limited to the experiments'
      resultant gene list; and finally the de novo Consolidation method uses several
      measurements of pathway similarity, that finds static pathway clusters
      independent of any given experiment. RESULTS: We demonstrate that the three
      consolidation methods provide unified yet different functional insights of a
      resultant gene set derived from a genome-wide profiling experiment. Results from
      the methods are presented, demonstrating their applications in biological studies
      and comparing with a pathway web-based framework that also combines several
      pathway databases. Additionally a web-based consolidation framework that
      encompasses all three methods discussed in this paper, Pathway Distiller
      (http://cbbiweb.uthscsa.edu/PathwayDistiller), is established to allow
      researchers access to the methods and example microarray data described in this
      manuscript, and the ability to analyze their own gene list by using our unique
      consolidation methods. CONCLUSIONS: By combining several pathway systems,
      implementing different, but complementary pathway consolidation methods, and
      providing a user-friendly web-accessible tool, we have enabled users the ability
      to extract functional explanations of their genome wide experiments.

PMID- 23134637
TI  - A comparison of statistical methods for genomic selection in a mice population.
AB  - BACKGROUND: The availability of high-density panels of SNP markers has opened new
      perspectives for marker-assisted selection strategies, such that genotypes for
      these markers are used to predict the genetic merit of selection candidates.
      Because the number of markers is often much larger than the number of phenotypes,
      marker effect estimation is not a trivial task. The objective of this research
      was to compare the predictive performance of ten different statistical methods
      employed in genomic selection, by analyzing data from a heterogeneous stock mice
      population. RESULTS: For the five traits analyzed (W6W: weight at six weeks, WGS:
      growth slope, BL: body length, %CD8+: percentage of CD8+ cells, CD4+/ CD8+: ratio
      between CD4+ and CD8+ cells), within-family predictions were more accurate than
      across-family predictions, although this superiority in accuracy varied markedly
      across traits. For within-family prediction, two kernel methods, Reproducing
      Kernel Hilbert Spaces Regression (RKHS) and Support Vector Regression (SVR), were
      the most accurate for W6W, while a polygenic model also had comparable
      performance. A form of ridge regression assuming that all markers contribute to
      the additive variance (RR_GBLUP) figured among the most accurate for WGS and BL,
      while two variable selection methods ( LASSO and Random Forest, RF) had the
      greatest predictive abilities for %CD8+ and CD4+/ CD8+. RF, RKHS, SVR and
      RR_GBLUP outperformed the remainder methods in terms of bias and inflation of
      predictions. CONCLUSIONS: Methods with large conceptual differences reached very
      similar predictive abilities and a clear re-ranking of methods was observed in
      function of the trait analyzed. Variable selection methods were more accurate
      than the remainder in the case of %CD8+ and CD4+/CD8+ and these traits are likely
      to be influenced by a smaller number of QTL than the remainder. Judged by their
      overall performance across traits and computational requirements, RR_GBLUP, RKHS
      and SVR are particularly appealing for application in genomic selection.

PMID- 23134638
TI  - HvCKX2 gene silencing by biolistic or Agrobacterium-mediated transformation in
      barley leads to different phenotypes.
AB  - BACKGROUND: CKX genes encode cytokinin dehydrogenase enzymes (CKX), which
      metabolize cytokinins in plants and influence developmental processes. The genes
      are expressed in different tissues and organs during development; however, their
      exact role in barley is poorly understood. It has already been proven that RNA
      interference (RNAi)-based silencing of HvCKX1 decreased the CKX level, especially
      in those organs which showed the highest expression, i.e. developing kernels and
      roots, leading to higher plant productivity and higher mass of the roots [1]. The
      same type of RNAi construct was applied to silence HvCKX2 and analyze the
      function of the gene. Two cultivars of barley were transformed with the same
      silencing and selection cassettes by two different methods: biolistic and via
      Agrobacterium. RESULTS: The mean Agrobacterium-mediated transformation efficiency
      of Golden Promise was 3.47% (+/-2.82). The transcript level of HvCKX2 in
      segregating progeny of T(1) lines was decreased to 34%. The reduction of the
      transcript in Agrobacterium-derived plants resulted in decreased CKX activity in
      the developing and developed leaves as well as in 7 DAP (days after pollination)
      spikes. The final phenotypic effect was increased productivity of T(0) plants and
      T(1) lines. Higher productivity was the result of the higher number of seeds and
      higher grain yield. It was also correlated with the higher 1000 grain weight,
      increased (by 7.5%) height of the plants and higher (from 0.5 to 2) numbers of
      spikes. The transformation efficiency of Golden Promise after biolistic
      transformation was more than twice as low compared to Agrobacterium. The
      transcript level in segregating progeny of T(1) lines was decreased to 24%.
      Otherwise, the enzyme activity found in the leaves of the lines after biolistic
      transformation, especially in cv. Golden Promise, was very high, exceeding the
      relative level of the control lines. These unbalanced ratios of the transcript
      level and the activity of the CKX enzyme negatively affected kernel germination
      or anther development and as a consequence setting the seeds. The final
      phenotypic effect was the decreased productivity of T(0) plants and T(1) lines
      obtained via the biolistic silencing of HvCKX2. CONCLUSION: The phenotypic
      result, which was higher productivity of silenced lines obtained via
      Agrobacterium, confirms the hypothesis that spatial and temporal differences in
      expression contributed to functional differentiation. The applicability of
      Agrobacterium-mediated transformation for gene silencing of developmentally
      regulated genes, like HvCKX2, was proven. Otherwise low productivity and
      disturbances in plant development of biolistic-silenced lines documented the
      unsuitability of the method. The possible reasons are discussed.

PMID- 23134639
TI  - Quantum interferences and electron transfer in photosystem I.
AB  - We have studied the electron transfer occurring in the photosystem I (PSI)
      reaction center from the special pair to the first iron-sulfur cluster.
      Electronic structure calculations performed at the DFT level were employed to
      determine the on-site energies of the fragments comprising PSI, as well as the
      charge transfer integrals between neighboring pairs. This electronic Hamiltonian
      was then used to compute the charge transfer dynamics, using the stochastic
      surrogate Hamiltonian approach to account for the coherent propagation of the
      electronic density but also for its energy relaxation and decoherence. These
      simulations give reasonable transfer time ranging from subpicoseconds to
      nanoseconds and predict coherent oscillations for several picoseconds. Due to
      these long-lasting coherences, the propagation of the electronic density can be
      enhanced or inhibited by quantum interferences. The impact of random fluctuations
      and asymmetries on these interferences is then discussed. Random fluctuations
      lead to a classical transport where both constructive and destructive quantum
      interferences are suppressed. Finally it is shown that an energy difference of
      0.15 eV between the on-site energies of the phylloquinones leads to a highly
      efficient electron transfer even in presence of strong random fluctuations. 

PMID- 23134640
TI  - A spatial model to predict the incidence of neural tube defects.
AB  - BACKGROUND: Environmental exposure may play an important role in the incidences
      of neural tube defects (NTD) of birth defects. Their influence on NTD may likely
      be non-linear; few studies have considered spatial autocorrelation of residuals
      in the estimation of NTD risk. We aimed to develop a spatial model based on
      generalized additive model (GAM) plus cokriging to examine and model the expected
      incidences of NTD and make the inference of the incidence risk. METHODS: We
      developed a spatial model to predict the expected incidences of NTD at village
      level in Heshun County, Shanxi Province, China, a region with high NTD cases. GAM
      was used to establish linear and non-linear relationships between local
      covariates and the expected NTD incidences. We examined the following village
      level covariates in the model: projected coordinates, soil types, lithodological
      classes, distance to watershed, rivers, faults and major roads, annual average
      fertilizer uses, fruit and vegetable production, gross domestic product, and the
      number of doctors. The residuals from GAM were assumed to be spatially auto
      correlative and cokriged with regional residuals to improve the prediction. Our
      approach was compared with three other models, universal kriging, generalized
      linear regression and GAM. Cross validation was conducted for validation.
      RESULTS: Our model predicted the expected incidences of NTD well, with a good CV
      R2 of 0.80. Important predictive factors included the fertilizer uses, locations
      of the centroid of each village, the shortest distance to rivers and faults and
      lithological classes with significant spatial autocorrelation of residuals. Our
      model out-performed the other three methods by 16% or more in term of R2.
      CONCLUSIONS: The variance explained by our model was approximately 80%. This
      modeling approach is useful for NTD epidemiological studies and intervention
      planning.

PMID- 23134641
TI  - Expression of Nav1.7 in DRG neurons extends from peripheral terminals in the skin
      to central preterminal branches and terminals in the dorsal horn.
AB  - BACKGROUND: Sodium channel Nav1.7 has emerged as a target of considerable
      interest in pain research, since loss-of-function mutations in SCN9A, the gene
      that encodes Nav1.7, are associated with a syndrome of congenital insensitivity
      to pain, gain-of-function mutations are linked to the debiliting chronic pain
      conditions erythromelalgia and paroxysmal extreme pain disorder, and upregulated
      expression of Nav1.7 accompanies pain in diabetes and inflammation. Since Nav1.7
      has been implicated as playing a critical role in pain pathways, we examined by
      immunocytochemical methods the expression and distribution of Nav1.7 in rat
      dorsal root ganglia neurons, from peripheral terminals in the skin to central
      terminals in the spinal cord dorsal horn. RESULTS: Nav1.7 is robustly expressed
      within the somata of peptidergic and non-peptidergic DRG neurons, and along the
      peripherally- and centrally-directed C-fibers of these cells. Nav1.7 is also
      expressed at nodes of Ranvier in a subpopulation of Adelta-fibers within sciatic
      nerve and dorsal root. The peripheral terminals of DRG neurons within skin,
      intraepidermal nerve fibers (IENF), exhibit robust Nav1.7 immunolabeling. The
      central projections of DRG neurons in the superficial lamina of spinal cord
      dorsal horn also display Nav1.7 immunoreactivity which extends to presynaptic
      terminals. CONCLUSIONS: The expression of Nav1.7 in DRG neurons extends from
      peripheral terminals in the skin to preterminal central branches and terminals in
      the dorsal horn. These data support a major contribution for Nav1.7 in pain
      pathways, including action potential electrogenesis, conduction along axonal
      trunks and depolarization/invasion of presynaptic axons. The findings presented
      here may be important for pharmaceutical development, where target engagement in
      the right compartment is essential.

PMID- 23134642
TI  - Energize your practice!

PMID- 23134643
TI  - Strategies for reducing the risk of respiratory syncytial virus infection in
      infants and young children: a Canadian nurses' perspective.
AB  - Respiratory syncytial virus (RSV) infections are prevalent globally and can cause
      substantial morbidity in infants and young children. The virus is easily
      transmitted by direct hand-to-hand contact and can lead to serious respiratory
      disease and hospitalization, particularly in premature infants and children with
      certain medical conditions. Educating families with young children, especially
      those in remote rural regions, regarding the potential adverse health outcomes of
      RSV infection and measures to reduce the risk of transmitting or acquiring RSV
      has been a key focus of the health care system in Canada. Geographic, cultural,
      and socioeconomic factors present formidable challenges to the execution of this
      endeavor. Therefore, it is critical to develop and systematically implement
      effective educational programs for both families and health care providers. In
      Canada, nurses play a critical role in education and counseling. In this review,
      we share our perspectives and suggest empirical practices that may be applicable
      worldwide.

PMID- 23134644
TI  - Identifying and ensuring optimal care for all children at risk of developing
      serious respiratory syncytial virus disease: a Canadian nurses' perspective.
AB  - Globally, respiratory syncytial virus (RSV) infection causes substantial
      morbidity in infants and young children, particularly those with specific risk
      factors (e.g., prematurity, chronic lung and congenital heart disease).
      Supportive measures are the mainstay of care for RSV-related disease. In the
      absence of medical treatments, RSV prophylaxis (RSVP) with palivizumab is
      recommended for high-risk patients to help reduce the risk of developing serious
      disease. Geographic distances, language and cultural barriers, and other factors
      can impede effective education of caregivers regarding the potential impact of
      RSV disease and benefits of RSVP compliance. We present our experiences
      developing successful Canadian RSVP programs, organized through a dedicated
      coordinator or small group of health care staff. These programs focus on
      identifying all infants and young children eligible for RSVP, effectively
      educating health care staff and family caregivers, developing educational tools
      that consider language and cultural factors, and interdisciplinary collaboration
      and networking throughout the health care system.

PMID- 23134645
TI  - Practical resources for nurses and other health care providers involved in the
      care of children at risk for respiratory syncytial virus infection.
AB  - Health care staff and families with young children are often unware of the ease
      of respiratory syncytial virus (RSV) spread and potential clinical consequences
      of serious respiratory illness. Successful Canadian RSV prophylaxis (RSVP)
      programs (a) provide practical educational resources on RSV and respiratory
      disease that consider language and cultural barriers; (b) develop policies to
      identify all children eligible for RSVP with palivizumab; (c) emphasize
      compliance with RSVP, particularly during patient transfer between hospitals,
      community clinics, and remote outpost centers; and (d) establish collaborative
      networks to help ensure optimum RSVP compliance for all high-risk children.
      Herein, we share practical resources and key educational references for
      counseling of caregivers with infants or young children at risk for RSV
      infection, and health care providers participating in RSVP program development.

PMID- 23134646
TI  - Owning your professional development.
AB  - Professional development encompasses more than simply attending continuing
      education courses or returning to school for advanced degrees. It can also refer
      to looking up an unfamiliar diagnosis, changing your practice based on new
      evidence, and networking with peers about professional issues. Professional
      growth also involves having curiosity, wanting to provide the best possible care
      for your patients, and exuding excellence as a nurse. It is about investing in
      yourself! In doing so, you are not only growing as a professional but also
      promoting the image of nursing. Several national initiatives, such as Magnet and
      the Institute of Medicine's (IOM 's) Future of Nursing Report, are available to
      help improve and transform health care, and also to hopefully help motivate us.1
      However, the impetus for professional development needs to come from within each
      individual nurse.

PMID- 23134647
TI  - Tweets, friends, and links: the use of social media by NICU health care
      providers.
AB  - Most of us are connected in some way to contacts through social media. Not only
      is it a great way to keep in touch and up-to-date but can also be a way to
      communicate with parents or guardians of patients in the NICU. However, along
      with the benefits comes the potential for abuse and or the unintentional
      disclosure of patient information.

PMID- 23134648
TI  - Subcutaneous fat necrosis: a complication of neuroprotective cooling.
AB  - Because neuroprotective cooling for hypoxic ischemic encephalopathy (HIE )
      becomes more commonplace in NICU s, health care providers should be familiar with
      the complications of this therapy. Therapeutic cooling improves
      neurodevelopmental outcomes and has relatively few side effects. One unexpected
      outcome that has been reported is subcutaneous fat necrosis (SCFN). This column
      describes the problem, and recommends that NICU staff be vigilant in their
      observation for, as well as timely in their interventions to help prevent SCFN.

PMID- 23134649
TI  - Hyaluronidase for extravasation management.

PMID- 23134653
TI  - Hypothermia in trauma patients: predicting the big chill.
AB  - Physicians commonly ignore hypothermia, an often-underappreciated event
      associated with mortality in trauma patients, in general due to its prevalence
      and belief that it is secondary to the injury itself (secondary hypothermia).
      Over the past several decades, hypothermia in trauma has been studied concerning
      its effects on mortality; however, very little has been done to identify the
      major risk factors associated with it. The study by Lapostolle and colleagues has
      attempted to incorporate environmental risk factors and prehospital care along
      with more traditional variables for the prediction of hypothermia at admission. 

PMID- 23134654
TI  - Tendon vibration attenuates superficial venous vessel response of the resting
      limb during static arm exercise.
AB  - BACKGROUND: The superficial vein of the resting limb constricts sympathetically
      during exercise. Central command is the one of the neural mechanisms that
      controls the cardiovascular response to exercise. However, it is not clear
      whether central command contributes to venous vessel response during exercise.
      Tendon vibration during static elbow flexion causes primary muscle spindle
      afferents, such that a lower central command is required to achieve a given force
      without altering muscle force. The purpose of this study was therefore to
      investigate whether a reduction in central command during static exercise with
      tendon vibration influences the superficial venous vessel response in the resting
      limb. METHODS: Eleven subjects performed static elbow flexion at 35% of maximal
      voluntary contraction with (EX + VIB) and without (EX) vibration of the biceps
      brachii tendon. The heart rate, mean arterial pressure, and rating of perceived
      exertion (RPE) in overall and exercising muscle were measured. The cross
      sectional area (CSAvein) and blood velocity of the basilic vein in the resting
      upper arm were assessed by ultrasound, and blood flow (BFvein) was calculated
      using both variables. RESULTS: Muscle tension during exercise was similar between
      EX and EX + VIB. However, RPEs at EX + VIB were lower than those at EX (P <0.05).
      Increases in heart rate and mean arterial pressure during exercise at EX + VIB
      were also lower than those at EX (P <0.05). CSAvein in the resting limb at EX
      decreased during exercise from baseline (P <0.05), but CSAvein at EX + VIB did
      not change during exercise. CSAvein during exercise at EX was smaller than that
      at EX + VIB (P <0.05). However, BFvein did not change during the protocol under
      either condition. The decreases in circulatory response and RPEs during EX + VIB,
      despite identical muscle tension, showed that activation of central command was
      less during EX + VIB than during EX. Abolishment of the decrease in CSAvein
      during exercise at EX + VIB may thus have been caused by a lower level of central
      command at EX + VIB rather than EX. CONCLUSION: Diminished central command
      induced by tendon vibration may attenuate the superficial venous vessel response
      of the resting limb during sustained static arm exercise.

PMID- 23134655
TI  - Proteomics identifies differentially expressed proteins in neonatal murine thymus
      compared with adults.
AB  - BACKGROUND: The thymus is an immune organ essential for life and plays a crucial
      role in the development of T cells. It undergoes a fetal to adult developmental
      maturation process occurring in mouse during the postnatal months. The molecular
      modifications underlying these ontogenic changes are essentially unknown. Here we
      used a differential proteomic-based technique (2D-Difference Gel Electrophoresis)
      coupled with matrix-assisted laser desorption/ionization-time of flight (MALDI
      TOF) mass spectrometry to search for key proteins in the postnatal development of
      the thymus. Eight different BALB/c mice were used in the study: four mice aged of
      1 day (neonatal) and four mice aged of 60 days (adult). Protein samples derived
      from thymus were labeled and run in 2D-PAGE (Two-Dimensional Polyacrylamide Gel
      Electrophoresis). One whole-thymus tissue from each mouse was run on gels and
      each gel containing a pooled sample of the eight mice was run in parallel. The
      pooled sample was set as the internal pool, containing equal amount of each
      protein extract used in the experiment. Gels were matched and compared with
      Difference In-gel Analysis software. Differential spots were picked, in-gel
      digested and peptide mass fingerprints were obtained. RESULTS: Among the
      differentially regulated proteins in neonatal thymus group, 111 proteins were
      identified by mass spectrometry, of which 95 proteins were up-regulated and 16
      proteins were down-regulated. The identified proteins belong to several
      functional categories, including cell proliferation, cycle and apoptosis,
      transcription regulation, signal transduction, nucleotide processing, proteolysis
      and translation, protein folding, metabolism, oxidoreduction, cytoskeleton,
      immune response, and embryonic development. The major interaction networks
      comprised of cellular function and maintenance, cellular assembly and
      organization, and metabolism were also identified by STRING analysis.
      CONCLUSIONS: The demonstrated molecular changes are relevant for understanding
      thymus development as well as neonatal immune function, and they provide the
      diagnostic disease markers. Further studies will be required to describe in
      detail the role of the identified proteins in thymus maturation and in the
      specific functions of neonatal thymus.

PMID- 23134656
TI  - The 2012 Garrod lecture: discovery of antibacterial drugs in the 21st century.
AB  - The discovery and development of antibacterial drugs in the twentieth century
      were major scientific and medical achievements that have had profound benefits
      for human society. However, in the twenty-first century the widespread global
      occurrence of bacteria resistant to the antibiotics and synthetic drugs
      discovered in the previous century threatens to reverse our ability to treat
      infectious diseases. Although some new drugs are in development they do not
      adequately cover growing medical needs. Furthermore, these drugs are mostly
      derivatives of older classes already in use and therefore prone to existing
      bacterial resistance mechanisms. Thus, new drug classes are urgently needed.
      Despite investment in antibacterial drug discovery, no new drug class has been
      discovered in the past 20 years. In this review, based upon my career as a
      research scientist in the field of antibacterial drug discovery, I consider some
      of the technical reasons for the recent failure and look to the future
      developments that may help to reverse the poor current success rate.
      Diversification of screening libraries to include new natural products will be
      important as well as ensuring that the promising drug hits arising from structure
      based drug design can achieve effective concentrations at their target sites
      within the bacterial cell.

PMID- 23134657
TI  - Detection of the plasmid-mediated KPC-2 carbapenem-hydrolysing enzyme in three
      unusual species of the Enterobacteriaceae family in Israel.

PMID- 23134658
TI  - Antimicrobial activity of the novel polymyxin derivative NAB739 tested against
      Gram-negative pathogens.
AB  - OBJECTIVES: In spite of reported nephrotoxicity, polymyxins have been reinstated
      as the last-line therapy to treat infections caused by Gram-negative bacterial
      strains that are resistant to other agents. NAB739 has a cyclic portion identical
      to that of polymyxin B, but its linear peptide portion consists of threonyl-d
      serinyl instead of diaminobutyryl-threonyl-diaminobutyryl. Therefore, NAB739
      lacks both of the positive charges present in the linear part of polymyxin B.
      Here, we compare the antibacterial activity of NAB739 with that of polymyxin B
      against a representative collection of contemporary Gram-negative bacteria.
      METHODS: NAB739 and polymyxin B MIC values were determined for 310 clinical
      isolates by the reference broth microdilution method according to CLSI document
      M07-A9 (2012). RESULTS: MIC(90)s of NAB739 for the subset consisting of polymyxin
      susceptible (MIC, <= 2 mg/L) clinical isolates of Escherichia coli (n=51),
      Klebsiella pneumoniae (n=50), Acinetobacter spp. (n=49) and Pseudomonas
      aeruginosa (n=49) were 2, 2, 8 and 16 mg/L, respectively. For polymyxin-non
      susceptible strains of E. coli (n=12), K. pneumoniae (n=11), Acinetobacter spp.
      (n=11) and P. aeruginosa (n=14) the NAB739 MIC(90) was >= 64 mg/L. CONCLUSIONS:
      The MIC(90) of NAB739 for polymyxin-susceptible strains of E. coli and K.
      pneumoniae was identical to and 2-fold higher than that of polymyxin B,
      respectively. For polymyxin-susceptible strains of Acinetobacter spp. and P.
      aeruginosa, the MIC(90) of NAB739 was 4-fold and 8-fold higher than that of
      polymyxin B, respectively. For polymyxin-non-susceptible strains of all these
      species, the MIC(90) values of NAB739 were high and 2- to 4-fold higher than
      those of polymyxin B.

PMID- 23134659
TI  - Design and synthesis of procollagen C-proteinase inhibitors.
AB  - Non-peptidic inhibitors of procollagen C-proteinase (PCP) were designed from
      substrate leads. Compounds were optimized for potency and selectivity, with N
      substituted aryl sulfonamide hydroxamates having the best combination of these
      properties. Compounds 89 and 60 have IC(50) values of 10 and 80 nM, respectively,
      against PCP; excellent selectivity over MMP's 1, 2, and 9; and activity in cell
      based collagen deposition assays.

PMID- 23134660
TI  - Cortical atrophy in presymptomatic Alzheimer's disease presenilin 1 mutation
      carriers.
AB  - BACKGROUND: Sporadic late-onset Alzheimer's disease (AD) dementia has been
      associated with a 'signature' of cortical atrophy in paralimbic and heteromodal
      association regions measured with MRI. OBJECTIVE: To investigate whether a
      similar pattern of cortical atrophy is present in presymptomatic presenilin 1
      E280A mutation carriers an average of 6 years before clinical symptom onset.
      METHODS: 40 cognitively normal volunteers from a Colombian population with
      familial AD were included; 18 were positive for the AD-associated presenilin 1
      mutation (carriers, mean age=38) whereas 22 were non-carriers. T1-weighted
      volumetric MRI images were acquired and cortical thickness was measured. A priori
      regions of interest from our previous work were used to obtain thickness from AD
      signature regions. RESULTS: Compared to non-carriers, presymptomatic presenilin 1
      mutation carriers exhibited thinner cortex within the AD-signature summary
      measure (p<0.008). Analyses of individual regions demonstrated thinner angular
      gyrus, precuneus and superior parietal lobule in carriers compared to non
      carriers, with trend-level effects in the medial temporal lobe. CONCLUSION:
      Results demonstrate that cognitively normal individuals genetically determined to
      develop AD have a thinner cerebral cortex than non-carriers in regions known to
      be affected by typical late-onset sporadic AD. These findings provide further
      support for the hypothesis that cortical atrophy is present in preclinical AD
      more than 5 years prior to symptom onset. Further research is needed to determine
      whether this method could be used to characterise the age-dependent trajectory of
      cortical atrophy in presymptomatic stages of AD.

PMID- 23134661
TI  - Persistent cognitive impairment, hippocampal atrophy and EEG changes in sepsis
      survivors.
AB  - OBJECTIVES: The objective of this preliminary study was to explore long-term
      changes in neurobehavioral parameters, brain morphology and
      electroencephalography of sepsis patients who received intensive care compared to
      non-septic intensive care unit (ICU) patients. METHODS: Two-centre follow-up
      study 6-24 months after discharge from hospital using published norms and
      existing databases of healthy controls for comparison. Patients included 25
      septic and 19 non-septic ICU survivors who were recruited from two ICUs of a
      university and community hospital. Measurements used include brain morphology,
      standard electroencephalography, cognition and psychiatric health and health
      related quality of life. RESULTS: Sepsis survivors showed cognitive deficits in
      verbal learning and memory and had a significant reduction of left hippocampal
      volume compared to healthy controls. Moreover, sepsis and to some extent non
      septic ICU patients had more low-frequency activity in the EEG indicating
      unspecific brain dysfunction. No differences were found in health-related quality
      of life, psychological functioning or depressive symptoms, and depression could
      be ruled out as a confounding factor. CONCLUSIONS: This study demonstrates
      permanent cognitive impairment in several domains in both septic and non-septic
      ICU survivors and unspecific brain dysfunction. In the sepsis group, left-sided
      hippocampal atrophy was found compared to healthy controls. Further study is
      needed to clarify what contribution sepsis and other factors at the ICU make to
      these outcomes. Specific neuroprotective therapies are warranted to prevent
      persisting brain changes in ICU patients.

PMID- 23134662
TI  - Preoperative and postoperative 1H-MR spectroscopy changes in frontal deep white
      matter and the thalamus in idiopathic normal pressure hydrocephalus.
AB  - BACKGROUND: In a previous study we found significantly decreased N-acetyl
      aspartate (NAA) and total N-acetyl (tNA) groups in the thalamus of patients with
      idiopathic normal pressure hydrocephalus (iNPH) compared with healthy individuals
      (HI). No significant difference between the groups could be found in the frontal
      deep white matter (FDWM). OBJECTIVE: The primary aim of this study was to
      investigate if these metabolites in the thalamus were normalised after shunt
      surgery. The secondary aim was to investigate postoperative metabolic changes in
      FDWM. SUBJECTS AND METHODS: Fourteen patients with iNPH, mean age 74 years, and
      15 HI, also mean age 74 years, were examined. Assessment of a motor score (MOSs)
      was performed before and after shunt surgery. Absolute quantitative (1)H-MR
      spectroscopy (1.5 T, volumes of interest 2.5-3 ml) was performed on the patients
      in the FDWM and in the thalamus, before and 3 months after shunt surgery, and
      also once on the HI. The following metabolites were analysed: tNA, NAA, total
      creatine, total choline (tCho), myo-inositol (mIns), glutamate and lactate
      concentrations. MRI volumetric calculations of the lateral ventricles were also
      performed. RESULTS: At 3 months postoperatively, we found no significant changes
      of tNA or NAA in the thalamus. In contrast, in the FDWM, there was a significant
      increase of tCho (p=0.01) and a borderline significant decrease of mIns (p=0.06).
      12/14 patients were shunt responders (motor function). Median reduction of the
      lateral ventricle was 16%. A weak correlation between MOS and ventricular
      reduction was seen. CONCLUSIONS: Normalisation of thalamic tNA and NAA could not
      be detected postoperatively. The increased tCho and decreased mIns in the FDWM
      postoperatively might relate to clinical improvement.

PMID- 23134663
TI  - Atlas2 Cloud: a framework for personal genome analysis in the cloud.
AB  - BACKGROUND: Until recently, sequencing has primarily been carried out in large
      genome centers which have invested heavily in developing the computational
      infrastructure that enables genomic sequence analysis. The recent advancements in
      next generation sequencing (NGS) have led to a wide dissemination of sequencing
      technologies and data, to highly diverse research groups. It is expected that
      clinical sequencing will become part of diagnostic routines shortly. However,
      limited accessibility to computational infrastructure and high quality
      bioinformatic tools, and the demand for personnel skilled in data analysis and
      interpretation remains a serious bottleneck. To this end, the cloud computing and
      Software-as-a-Service (SaaS) technologies can help address these issues. RESULTS:
      We successfully enabled the Atlas2 Cloud pipeline for personal genome analysis on
      two different cloud service platforms: a community cloud via the Genboree
      Workbench, and a commercial cloud via the Amazon Web Services using Software-as-a
      Service model. We report a case study of personal genome analysis using our
      Atlas2 Genboree pipeline. We also outline a detailed cost structure for running
      Atlas2 Amazon on whole exome capture data, providing cost projections in terms of
      storage, compute and I/O when running Atlas2 Amazon on a large data set.
      CONCLUSIONS: We find that providing a web interface and an optimized pipeline
      clearly facilitates usage of cloud computing for personal genome analysis, but
      for it to be routinely used for large scale projects there needs to be a paradigm
      shift in the way we develop tools, in standard operating procedures, and in
      funding mechanisms.

PMID- 23134664
TI  - ST proteins, a new family of plant tandem repeat proteins with a DUF2775 domain
      mainly found in Fabaceae and Asteraceae.
AB  - BACKGROUND: Many proteins with tandem repeats in their sequence have been
      described and classified according to the length of the repeats: I) Repeats of
      short oligopeptides (from 2 to 20 amino acids), including structural cell wall
      proteins and arabinogalactan proteins. II) Repeats that range in length from 20
      to 40 residues, including proteins with a well-established three-dimensional
      structure often involved in mediating protein-protein interactions. (III) Longer
      repeats in the order of 100 amino acids that constitute structurally and
      functionally independent units. Here we analyse ShooT specific (ST) proteins, a
      family of proteins with tandem repeats of unknown function that were first found
      in Leguminosae, and their possible similarities to other proteins with tandem
      repeats. RESULTS: ST protein sequences were only found in dicotyledonous plants,
      limited to several plant families, mainly the Fabaceae and the Asteraceae. ST
      mRNAs accumulate mainly in the roots and under biotic interactions. Most ST
      proteins have one or several Domain(s) of Unknown Function 2775 (DUF2775). All
      deduced ST proteins have a signal peptide, indicating that these proteins enter
      the secretory pathway, and the mature proteins have tandem repeat oligopeptides
      that share a hexapeptide (E/D)FEPRP followed by 4 partially conserved amino
      acids, which could determine a putative N-glycosylation signal, and a fully
      conserved tyrosine. In a phylogenetic tree, the sequences clade according to
      taxonomic group. A possible involvement in symbiosis and abiotic stress as well
      as in plant cell elongation is suggested, although different STs could play
      different roles in plant development. CONCLUSIONS: We describe a new family of
      proteins called ST whose presence is limited to the plant kingdom, specifically
      to a few families of dicotyledonous plants. They present 20 to 40 amino acid
      tandem repeat sequences with different characteristics (signal peptide, DUF2775
      domain, conservative repeat regions) from the described group of 20 to 40 amino
      acid tandem repeat proteins and also from known cell wall proteins with repeat
      sequences. Several putative roles in plant physiology can be inferred from the
      characteristics found.

PMID- 23134665
TI  - Activity of pemetrexed and high-dose gefitinib in an EGFR-mutated lung
      adenocarcinoma with brain and leptomeningeal metastasis after response to
      gefitinib.
AB  - About 20% to 40% of patients with non-small cell lung cancer (NSCLC) will develop
      brain metastases during the natural course of their disease. The prognosis for
      such patients is very poor with limited survival. In addition to the standard
      whole brain radiation therapy (WBRT), some studies have shown that chemotherapy
      drugs and/or epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR
      TKI) can improve the outcome of these patients. Here, we report a stage IIIA
      patient who developed multiple brain metastases one year after operation. Oral
      gefitinib with concurrent WBRT were given as first-line therapy. Complete
      response and a 50-month progression-free survival (PFS) were obtained. Double
      dosage of gefitinib (500 mg per day) together with pemetrexed were given as the
      second-line therapy after the patient developed new brain lesions and
      leptomeningeal metastasis during the maintenance therapy of gefitinib. The PFS
      for the second-line therapy was six months. In total, the patient obtained an
      overall survival of 59 months since the first diagnosis of brain metastases.
      Mutational analysis showed a 15-nucleotide deletion and a missense mutation in
      exon 19 of the EGFR gene, and a missense mutation at codon 12 of the K-ras gene.
      These underlying genetic changes might partially explain the long-term survival
      of this patient after brain metastases when treated with concurrent or sequential
      therapies of EGFR-TKI, radiotherapy and chemotherapy.

PMID- 23134666
TI  - QTL affecting stress response to crowding in a rainbow trout broodstock
      population.
AB  - BACKGROUND: Genomic analyses have the potential to impact selective breeding
      programs by identifying markers that serve as proxies for traits which are
      expensive or difficult to measure. Also, identifying genes affecting traits of
      interest enhances our understanding of their underlying biochemical pathways. To
      this end we conducted genome scans of seven rainbow trout families from a single
      broodstock population to identify quantitative trait loci (QTL) having an effect
      on stress response to crowding as measured by plasma cortisol concentration. Our
      goal was to estimate the number of major genes having large effects on this trait
      in our broodstock population through the identification of QTL. RESULTS: A genome
      scan including 380 microsatellite markers representing 29 chromosomes resulted in
      the de novo construction of genetic maps which were in good agreement with the
      NCCCWA genetic map. Unique sets of QTL were detected for two traits which were
      defined after observing a low correlation between repeated measurements of plasma
      cortisol concentration in response to stress. A highly significant QTL was
      detected in three independent analyses on Omy16, many additional suggestive and
      significant QTL were also identified. With linkage-based methods of QTL analysis
      such as half-sib regression interval mapping and a variance component method, we
      determined that the significant and suggestive QTL explain about 40-43% and 13
      27% of the phenotypic trait variation, respectively. CONCLUSIONS: The cortisol
      response to crowding stress is a complex trait controlled in a sub-sample of our
      broodstock population by multiple QTL on at least 8 chromosomes. These QTL are
      largely different from others previously identified for a similar trait,
      documenting that population specific genetic variants independently affect
      cortisol response in ways that may result in different impacts on growth. Also,
      mapping QTL for multiple traits associated with stress response detected trait
      specific QTL which indicate the significance of the first plasma cortisol
      measurement in defining the trait. Fine mapping these QTL can lead towards the
      identification of genes affecting stress response and may influence approaches to
      selection for this economically important stress response trait.

PMID- 23134667
TI  - Inhibition of TGF-beta signaling by the fungal lactones (S)-curvularin,
      dehydrocurvularin, oxacyclododecindione and galiellalactone.
AB  - TGF-beta is a multifunctional cytokine that regulates cell proliferation,
      differentiation, apoptosis and extracellular matrix production. Deregulation of
      TGF-beta production or signaling plays a pivotal role in a variety of
      pathological processes such as cancer, metastasis, angiogenesis and fibrosis.
      Therefore, TGF-beta inhibitors should be promising therapeutic agents for the
      suppression of cancer progression and metastasis as well as fibrotic disorders.
      In a screening program of natural compounds from fungi inhibiting the TGF-beta
      dependent expression of a reporter gene in HepG2 cells, we found that the fungal
      lactones (S)-curvularin, dehydrocurvularin, oxacyclododecindione and
      galiellalactone inhibited the binding of the activated Smad2/3 transcription
      factors to the DNA and antagonized the cellular effects of TGF-beta including
      reporter gene activation and expression of TGF-beta induced genes in HepG2 and
      MDA-MB-231 cells. The most active compound oxacyclododecindione inhibited TGF
      beta dependent reporter activity with IC50-values of 190-217 nM. In an in vitro
      angiogenesis assay, the fungal lactones strongly decreased the formation of
      capillary-like tubules of MDA-MB-231 cells on Matrigel.

PMID- 23134668
TI  - Postoperative lumbar spinal stenosis after intertransverse fusion with granules
      of hydroxyapatite: a case report.
AB  - In the present case of postoperative lumbar spinal stenosis after non
      instrumented intertransverse fusion with granules of hydroxyapatite (HA), bone
      union was not completed and the patient felt the recurrence of his symptoms
      within two years. We performed re-decompression with fusion, and in hematoxylin
      and eosin staining of HA granulation harvested during revision surgery, fibrous
      tissue with hyaline degeneration surrounded the cavity where the HA had existed.
      Multinuclear giant cells and lymphocytes infiltrated some parts of the marginal
      layer of the cavity, and no obvious bony bridge had regenerated from autologous
      bone. No tartrate-resistant acid phosphate (TRAP) -positive osteoclasts could be
      seen in the new bone, suggesting that the activity of osteoclasts in the new bone
      decreased during the seven years after the primary surgery. VIRTUAL SLIDES: The
      virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/3483360258050263.

PMID- 23134669
TI  - Contextual determinants of health behaviours in an aboriginal community in
      Canada: pilot project.
AB  - BACKGROUND: Rapid change in food intake, physical activity, and tobacco use in
      recent decades have contributed to the soaring rates of obesity, type 2 diabetes
      and cardiovascular disease (CVD) in Aboriginal populations living in Canada. The
      nature and influence of contextual factors on Aboriginal health behaviours are
      not well characterized. METHODS: To describe the contextual determinants of
      health behaviours associated with cardiovascular risk factors on the Six Nations
      reserve, including the built environment, access and affordability of healthy
      foods, and the use of tobacco.In this cross-sectional study, 63 adults from the
      Six Nations Reserve completed the modified Neighbourhood Environment Walkability
      Scale (NEWS), questionnaire assessing food access and availability, tobacco
      pricing and availability, and the Environmental Profile of Community Health
      (EPOCH) tool. RESULTS: The structured environment of Six Nations Reserve scored
      low for walkability, street connectivity, aesthetics, safety, and access to
      walking and cycling facilities. All participants purchased groceries off-reserve,
      although fresh fruits and vegetables were reported to be available and affordable
      both on and off-reserve. On average $151/week is spent on groceries per family.
      Ninety percent of individuals report tobacco use is a problem in the community.
      Tobacco is easily accessible for children and youth, and only three percent of
      community members would accept increased tobacco taxation as a strategy to reduce
      tobacco access. CONCLUSIONS: The built environment, access and affordability of
      healthy food and tobacco on the Six Nations Reserve are not perceived favourably.
      Modification of these contextual factors described here may reduce adverse health
      behaviours in the community.

PMID- 23134670
TI  - A systematic model of the LC-MS proteomics pipeline.
AB  - MOTIVATION: Mass spectrometry is a complex technique used for large-scale protein
      profiling with clinical and pharmaceutical applications. While individual
      components in the system have been studied extensively, little work has been done
      to integrate various modules and evaluate them from a systems point of view.
      RESULTS: In this work, we investigate this problem by putting together the
      different modules in a typical proteomics work flow, in order to capture and
      analyze key factors that impact the number of identified peptides and quantified
      proteins, protein quantification error, differential expression results, and
      classification performance. The proposed proteomics pipeline model can be used to
      optimize the work flow as well as to pinpoint critical bottlenecks worth
      investing time and resources into for improving performance. Using the model
      based approach proposed here, one can study systematically the critical problem
      of proteomic biomarker discovery, by means of simulation using ground-truthed
      synthetic MS data.

PMID- 23134671
TI  - Pro-anorexia and pro-recovery photo sharing: a tale of two warring tribes.
AB  - BACKGROUND: There is widespread use of the Internet to promote anorexia as a
      lifestyle choice. Pro-anorexia content can be harmful for people affected or at
      risk of having anorexia. That movement is actively engaged in sharing photos on
      social networks such as Flickr. OBJECTIVE: To study the characteristics of the
      online communities engaged in disseminating content that encourages eating
      disorders (known as "pro-anorexia") and to investigate if the posting of such
      content is discouraged by the posting of recovery-oriented content. METHODS: The
      extraction of pro-anorexia and pro-recovery photographs from the photo sharing
      site Flickr pertaining to 242,710 photos from 491 users and analyzing four
      separate social networks therein. RESULTS: Pro-anorexia and pro-recovery
      communities interact to a much higher degree among themselves than what is
      expected from the distribution of contacts (only 59-72% of contacts but 74-83% of
      comments are made to members inside the community). Pro-recovery users employ
      similar words to those used by pro-anorexia users to describe their photographs,
      possibly in order to ensure that their content appears when pro-anorexia users
      search for images. Pro-anorexia users who are exposed to comments from the
      opposite camp are less likely to cease posting pro-anorexia photographs than
      those who do not receive such comments (46% versus 61%), and if they cease, they
      do so approximately three months later. Our observations show two highly active
      communities, where most interaction is within each community. However, the pro
      recovery community takes steps to ensure that their content is visible to the pro
      anorexia community, both by using textual descriptions of their photographs that
      are similar to those used by the pro-anorexia group and by commenting to pro
      anorexia content. The latter activity is, however, counterproductive, as it
      entrenches pro-anorexia users in their stance. CONCLUSIONS: Our results highlight
      the nature of pro-anorexia and pro-recovery photo sharing and accentuate the need
      for clinicians to be aware of such content and its effect on their patients. Our
      findings suggest that some currently used interventions are not useful in helping
      pro-anorexia users recover. Thus, future work should focus on new intervention
      methods, possibly tailored to individual characteristics.

PMID- 23134672
TI  - New conclusive data on human myocardial dysfunction induced by acidosis.
AB  - Acidosis is one of the major consequences of hemodynamic instability in shock
      state patients directly associated with multiple organ failure evolution and
      death. Most studies on the hemodynamic consequences of acidosis have been
      experimental, nonhuman studies with severe acidosis, and thus far from the most
      common clinical situations. Schotola and colleagues offer a new approach to human
      failing myocardium where the authors highlight, ex vivo, the deleterious
      hemodynamic consequences of mild acidosis. Their work strengthens the current
      view of the urgent need to discover new efficient and nondeleterious therapy for
      the treatment of acidosis. 

PMID- 23134673
TI  - A descriptive study on health workforce performance after decentralisation of
      health services in Uganda.
AB  - BACKGROUND: Uganda, like many developing countries, is committed to achieving
      the Millennium Development Goals (MDGs) by 2015. However, serious challenges
      prove to hamper the attainment of these goals, particularly the health related
      MDGs. A major challenge relates to the human resources for health. The health
      system in Uganda was decentralised in the 1990s. Despite the health sector
      reforms, the services have remained significantly deficient and performance of
      health workers is thought to be one of the contributing factors. The purpose of
      this study was, therefore, to investigate the performance of health workers after
      decentralisation of the health services in Uganda in order to identify and
      suggest possible areas for improvement. METHODS: A cross-sectional descriptive
      survey, using quantitative research methods was utilised. A structured self
      administered questionnaire was used to collect quantitative data from 276 health
      workers in the districts of Kumi, Mbale, Sironko and Tororo in Eastern Uganda.
      The health workers included doctors, clinical officers, professional nurses and
      midwives. The sample was selected using stratified random sampling. The data was
      analysed using SPSS version 18.0 and included both univariate and bivariate
      analysis. The results were presented in tabular and text forms. RESULTS: The
      study revealed that even though the health workers are generally responsive to
      the needs of their clients, the services they provide are often not timely. The
      health workers take initiatives to ensure that they are available for work,
      although low staffing levels undermine these efforts. While the study shows that
      the health workers are productive, over half (50.4%) of them reported that their
      organisations do not have indicators to measure their individual performance. The
      findings indicate that the health workers are skilled and competent to perform
      their duties. In general, the results show that health workers are proficient,
      adaptive, proactive and client-oriented. CONCLUSION: Although Uganda is faced
      with a number of challenges as regards human resources for health, the findings
      show that the health workers that are currently working in the health facilities
      are enthusiastic to perform. This may serve as a motivator for the health workers
      to improve their performance and that of the health sector.

PMID- 23134675
TI  - Does occupational mobility influence health among working women? Comparing
      objective and subjective measures of work trajectories.
AB  - Occupational mobility is highly valued in American society, but is it
      consequential to women's health? Previous studies have yielded inconsistent
      results, but most measured occupational mobility by identifying transitions
      across occupational categories. Drawing from cumulative inequality theory, this
      study (1) compares objective and subjective measures of work trajectories and (2)
      examines the contributions of each to self-rated health. With 36 years of data
      from the National Longitudinal Survey of Mature Women (1967-2003), growth curve
      models are used to estimate the effects of middle-aged work trajectories on
      health among 2,503 U.S. women. Work trajectories as measured by the Duncan
      Socioeconomic Index predict health, but not after adjustment for perceived work
      trajectories and status characteristics. The findings reveal that subjective
      measures of occupational mobility provide important information for assessing
      health consequences of work transitions and that downward occupational mobility
      in middle age is deleterious to women's health in later life.

PMID- 23134674
TI  - Identification of genes involved in the ACC-mediated control of root cell
      elongation in Arabidopsis thaliana.
AB  - BACKGROUND: Along the root axis of Arabidopsis thaliana, cells pass through
      different developmental stages. In the apical meristem repeated cycles of
      division increase the numbers of cells. Upon leaving the meristem, these cells
      pass the transition zone where they are physiologically and mechanically prepared
      to undergo subsequent rapid elongation. During the process of elongation
      epidermal cells increase their length by 300% in a couple of hours. When
      elongation ceases, the cells acquire their final size, shape and functions (in
      the differentiation zone). Ethylene administered as its precursor 1
      aminocyclopropane-1-carboxylic acid (ACC) is capable of inhibiting elongation in
      a concentration-dependent way. Using a microarray analysis, genes and/or
      processes involved in this elongation arrest are identified. RESULTS: Using a
      CATMA-microarray analysis performed on control and 3h ACC-treated roots, 240
      differentially expressed genes were identified. Quantitative Real-Time RT-PCR
      analysis of the 10 most up and down regulated genes combined with literature
      search confirmed the accurateness of the analysis. This revealed that inhibition
      of cell elongation is, at least partly, caused by restricting the events that
      under normal growth conditions initiate elongation and by increasing the
      processes that normally stop cellular elongation at the end of the
      elongation/onset of differentiation zone. CONCLUSIONS: ACC interferes with cell
      elongation in the Arabidopsis thaliana roots by inhibiting cells from entering
      the elongation process and by immediately stimulating the formation of cross
      links in cell wall components, diminishing the remaining elongation capacity.
      From the analysis of the differentially expressed genes, it becomes clear that
      many genes identified in this response, are also involved in several other kind
      of stress responses. This suggests that many responses originate from individual
      elicitors, but that somewhere in the downstream signaling cascade, these are
      converged to a 'common pathway'. Furthermore, several potential keyplayers, such
      as transcription factors and auxin-responsive genes, were identified by the
      microarray analysis. They await further analysis to reveal their exact role in
      the control of cell elongation.

PMID- 23134676
TI  - A novel reverse thermosensitive polymer to achieve temporary atraumatic vessel
      occlusion in infra-popliteal bypasses.
AB  - OBJECTIVE: The study aims to assess a novel thermosensitive polymer (LeGoo((r)))
      for distal vessel control during infra-popliteal (crural/pedal) bypass surgery in
      severe leg ischaemia. METHOD: Retrospective analysis of all distal bypasses from
      October 2009 to February 2012. Technical success, patency, limb salvage and
      amputation-free survival rates were analysed. RESULTS: Fifty-four infra-popliteal
      bypasses using the polymer were performed in 46 patients. The distal anastomosis
      was at the anterior tibial (n = 15, 28%), posterior tibial (n = 12, 22%),
      peroneal (n = 8, 15%), tibio-peroneal trunk (n = 8, 15%) and dorsalis pedis
      arteries (n = 11, 20%). Technical success was achieved in 51/54 (94.4%; failures:
      two inadequate haemostasis, one un-dissolved polymer). In-hospital duplex of the
      distal anastomosis showed a significant stenosis in two cases (4.3%). Outflow
      angioplasty was performed in three cases (two distal anastomotic, one run-off
      vessel, 5.6%). The 1-year patency rate was 76.2% (standard error (SE) 6.7%), limb
      salvage rate 79.3% (SE 6.7%). Amputation-free survival was 93.5% at 30 days (SE
      3.6%) and 67.5% at 1 year (SE 7.5%). CONCLUSION: This thermosensitive polymer is
      a potentially safe and useful atraumatic device to achieve a blood-less distal
      anastomotic field in infra-popliteal bypasses. The technique avoids other
      potentially traumatic methods of vessel control, which may be particularly
      important in patients with calcified distal vessels.

PMID- 23134677
TI  - Antibacterial activity of the human host defence peptide LL-37 and selected
      synthetic cationic lipids against bacteria associated with oral and upper
      respiratory tract infections.
AB  - OBJECTIVES: We aim to develop antibacterial peptide mimics resistant to protease
      degradation, with broad-spectrum activity at sites of infection. METHODS: The
      bactericidal activities of LL-37, ceragenins CSA-13, CSA-90 and CSA-92 and the
      spermine-conjugated dexamethasone derivative D2S were evaluated using MIC and MBC
      measurements. Gingival fibroblast counting, interleukin-8 (IL-8) and lactate
      dehydrogenase (LDH) release from keratinocytes (HaCat) were used to determine
      effects on cell growth, pro-inflammatory response and toxicity. RESULTS: All
      tested cationic lipids showed stronger bactericidal activity than LL-37.
      Incubation of Staphylococcus aureus with half the MIC of LL-37 led to the
      appearance of bacteria resistant to its bactericidal effects, but identical
      incubations with CSA-13 or D2S did not produce resistant bacteria. Cathelicidin
      LL-37 significantly increased the total number of gingival fibroblasts, but
      ceragenins and D2S did not alter gingival fibroblast growth. Cationic lipids
      showed no toxicity to HaCat cells at concentrations resulting in bacterial
      killing. CONCLUSIONS: These data suggest that cationic lipids such as ceragenins
      warrant further testing as potential novel antibacterial agents.

PMID- 23134678
TI  - Photodynamic inhibition of Trichophyton rubrum: in vitro activity and the role of
      oxidative and nitrosative bursts in fungal death.
AB  - OBJECTIVES: Antimicrobial photodynamic inhibition (aPI) is based on the use of a
      light source and a photosensitizer to kill pathogens. Little is known about aPI
      of dermatophytic fungi and its mechanism of action. We aimed to evaluate aPI of
      Trichophyton rubrum. METHODS: We performed tests using toluidine blue (TBO) as a
      photosensitizer and a 630 nm light-emitting diode (LED) as a source of light to
      target 12 T. rubrum isolates. Susceptibility testing with cyclopiroxolamine, time
      kill curves and quantification of reactive oxygen species (ROS), peroxynitrite
      (ONOO.) and nitric oxide (NO.) were performed. RESULTS: The optimal conditions
      for in vitro aPI were 10 mg/L for TBO and 48 J/cm(2) for LED; these conditions
      were fungicidal or inhibited >98% of fungal growth depending on the strain
      tested. LED or TBO treatment alone did not inhibit growth. The MICs of
      cyclopiroxolamine were 2.0 mg/L for 90% of the strains. Analysis of time-kill
      curves revealed that pathogen death occurred 24 h post-treatment. Quantification
      of ROS, ONOO. and NO. revealed improvement after aPI. CONCLUSIONS: Photodynamic
      inhibition was more efficient in promoting cell death than the antifungal
      cyclopiroxolamine against T. rubrum. ROS, ONOO. and NO. were important in the
      fungicidal activity of aPI. A suggested mechanism for this activity is that TBO
      is excited by LED light (630 nm), reacts with biomolecules and increases the
      availability of transition electrons and substrates for nitric oxide synthase,
      thereby increasing the oxidative and nitrosative bursts in the fungal cell.

PMID- 23134679
TI  - Searching for resistance genes to Bursaphelenchus xylophilus using high
      throughput screening.
AB  - BACKGROUND: Pine wilt disease (PWD), caused by the pinewood nematode (PWN;
      Bursaphelenchus xylophilus), damages and kills pine trees and is causing serious
      economic damage worldwide. Although the ecological mechanism of infestation is
      well described, the plant's molecular response to the pathogen is not well known.
      This is due mainly to the lack of genomic information and the complexity of the
      disease. High throughput sequencing is now an efficient approach for detecting
      the expression of genes in non-model organisms, thus providing valuable
      information in spite of the lack of the genome sequence. In an attempt to unravel
      genes potentially involved in the pine defense against the pathogen, we hereby
      report the high throughput comparative sequence analysis of infested and non
      infested stems of Pinus pinaster (very susceptible to PWN) and Pinus pinea (less
      susceptible to PWN). RESULTS: Four cDNA libraries from infested and non-infested
      stems of P. pinaster and P. pinea were sequenced in a full 454 GS FLX run,
      producing a total of 2,083,698 reads. The putative amino acid sequences encoded
      by the assembled transcripts were annotated according to Gene Ontology, to assign
      Pinus contigs into Biological Processes, Cellular Components and Molecular
      Functions categories. Most of the annotated transcripts corresponded to Picea
      genes-25.4-39.7%, whereas a smaller percentage, matched Pinus genes, 1.8-12.8%,
      probably a consequence of more public genomic information available for Picea
      than for Pinus. The comparative transcriptome analysis showed that when P.
      pinaster was infested with PWN, the genes malate dehydrogenase, ABA, water
      deficit stress related genes and PAR1 were highly expressed, while in PWN
      infested P. pinea, the highly expressed genes were ricin B-related lectin, and
      genes belonging to the SNARE and high mobility group families. Quantitative PCR
      experiments confirmed the differential gene expression between the two pine
      species. CONCLUSIONS: Defense-related genes triggered by nematode infestation
      were detected in both P. pinaster and P. pinea transcriptomes utilizing 454
      pyrosequencing technology. P. pinaster showed higher abundance of genes related
      to transcriptional regulation, terpenoid secondary metabolism (including some
      with nematicidal activity) and pathogen attack. P. pinea showed higher abundance
      of genes related to oxidative stress and higher levels of expression in general
      of stress responsive genes. This study provides essential information about the
      molecular defense mechanisms utilized by P. pinaster and P. pinea against PWN
      infestation and contributes to a better understanding of PWD.

PMID- 23134680
TI  - The anticancer drug Dp44mT inhibits T-cell activation and CD25 through a copper
      dependent mechanism.
AB  - The di-2-pyridylketone thiosemicarbazone Dp44mT is a metal-chelating compound
      that has been demonstrated to have potent activity as an anticancer agent. Here
      we report that it also has a dramatic inhibitory effect on T-cell activation in
      vitro. We found that 10 nM Dp44mT (IC(50) 3.2 nM) prevented the up-regulation of
      surface CD25, and completely suppressed the activation and proliferation of
      splenic T cells isolated from Mus musculus that were stimulated with either T
      cell receptor (TCR) cross-linking antibodies or phorbol ester plus ionomycin. In
      contrast, Dp44mT had no adverse effects on the survival of resting T cells. In
      addition, T cells stimulated in the presence of Dp44mT maintained the ability to
      up-regulate CD69 surface expression and secrete interleukin-2. Consistent with
      these observations, Dp44mT did not inhibit multiple canonical signals downstream
      of the TCR, including the nuclear factor of activated T cells. The effects of
      Dp44mT were easily mitigated by addition of nontoxic copper chelators or N
      acetylcysteine, indicating a role for copper and reactive oxygen species in its
      actions. Together, these findings suggest that Dp44mT may serve as a potent
      immunosuppressive agent that could complicate its use as a cancer therapeutic
      agent, but might have utility in the treatment of autoimmunity.

PMID- 23134681
TI  - Shaking the family tree: identification of novel and biologically active
      alternatively spliced isoforms across the KLF family of transcription factors.
AB  - Alternative splicing represents a unique post-transcriptional mechanism that
      increases the complexity of the eukaryotic proteome-generating protein isoforms
      whose functions can be novel, diverse, and/or even antagonistic when compared to
      its full-length transcript. The KLF family of genes consists of >=17 members,
      which are involved in the regulation of numerous critical cellular processes,
      including differentiation, cell proliferation, growth-related signal
      transduction, angiogenesis, and apoptosis. Using a strategy based on RT-PCR,
      selective cloning, and promoter-based assays of cancer-relevant genes, we
      identify and characterize the existence of multiple biologically active KLF
      splice forms across the entire family of proteins. We demonstrate biological
      function for a number of these isoforms. Furthermore, we highlight a possible
      functional interaction between full-length KLF4 and one of its splice variants in
      up-regulating cellular proliferation. Taken together, this report identifies for
      the first time a more complete view of the genomic and proteomic breadth and
      complexity of the KLF transcription factor family, revealing the existence of
      highly expressed and biologically active isoforms previously uncharacterized. In
      essence, knowing that these KLF isoforms exist provides the first step toward
      understanding the roles of these genes in human health and disease.

PMID- 23134682
TI  - Identification and profiling of miRNAs during herbivory reveals jasmonate
      dependent and -independent patterns of accumulation in Nicotiana attenuata.
AB  - BACKGROUND: Plant microRNAs (miRNAs) play key roles in the transcriptional
      responses to environmental stresses. However, the role of miRNAs in responses to
      insect herbivory has not been thoroughly explored. To identify herbivory
      responsive miRNAs, we identified conserved miRNAs in the ecological model plant
      Nicotiana attenuata whose interactions with herbivores have been well
      characterized in both laboratory and field studies. RESULTS: We identified 59
      miRNAs from 36 families, and two endogenous trans-acting small interfering RNAs
      (tasiRNA) targeted by miRNAs. We characterized the response of the precursor and
      mature miRNAs to simulated attack from the specialist herbivore Manduca sexta by
      quantitative PCR analysis and used ir-aoc RNAi transformants, deficient in
      jasmonate biosynthesis, to identify jasmonate-dependent and -independent miRNA
      regulation. Expression analysis revealed that groups of miRNAs and tasiRNAs were
      specifically regulated by either mechanical wounding or wounding plus oral
      secretions from M. sexta larvae, and these small RNAs were accumulated in
      jasmonate-dependent or -independent manners. Moreover, cDNA microarray analysis
      indicated that the expression patterns of the corresponding target genes were
      correlated with the accumulation of miRNAs and tasiRNAs. CONCLUSIONS: We show
      that a group of miRNAs and tasiRNAs orchestrates the expression of target genes
      involved in N. attenuata's responses to herbivore attack.

PMID- 23134683
TI  - Pulmonary artery sarcoma with angiosarcoma phenotype mimicking pleomorphic
      malignant fibrous histiocytoma: a case report.
AB  - Primary sarcomas of the major blood vessels can be classified based on location
      in relationship to the wall or by histologic type. Angiosarcomas are malignant
      neoplasms that arise from the endothelial lining of the blood vessels; those
      arising in the intimal compartment of pulmonary artery are rare. We report a case
      of pulmonary artery angiosarcoma in a 36-year old female with pulmonary masses.
      The patient had no other primary malignant neoplasm, thus excluding a metastatic
      lesion. Gross examination revealed a thickened right pulmonary artery and a
      necrotic and hemorrhagic tumor, filling and occluding the vascular lumen. The
      mass extended distally, within the pulmonary vasculature of the right lung.
      Microscopically, an intravascular undifferentiated tumor was identified. The
      tumor cells showed expression for vascular markers VEGFR, VEGFR3, PDGFRa, FGF,
      Ulex europaeus, FVIII, FLI-1, CD31 and CD34; p53 was overexpressed and Ki67
      proliferative rate was increased. Intravascular angiosarcomas are aggressive
      neoplasms, often associated with poor outcome.

PMID- 23134685
TI  - The use of pMRI to validate the identification of palpated bony landmarks.
AB  - Accurate palpation of lumbar spinous processes (SPs) is a key component of spinal
      assessment. It is also vital for the accurate measurement of spinal motion when
      using external skin marker-based measurement systems, which are being
      increasingly used to understand low back disorders and their management. The aim
      was to assess the accuracy of lumbar spinous process (SP) palpation using
      positional magnetic resonance imagery (MRI) (pMRI). Two experienced manual
      therapists palpated the L4 SP of nine pain-free participants in standing and
      prone lying. For each position, an MRI marker was attached over the SP and pMRI
      scanning was conducted. The position of the marker in relation to L4 on the MRI
      images was visually inspected, and measurements (mm) of the vertical distance
      from the superior/inferior aspect of the marker to the superior/inferior aspect
      of the L4 SP were used to determine palpation accuracy. 71% of Markers were
      correctly placed over the L4 SP. The magnitude of error for incorrectly placed
      markers was small, with the largest median distance of 2.7 mm (interquartile
      range (IQR) 0-3.6) recorded for one of the therapists palpating in prone lying.
      100% of markers were correctly placed either on L4 or within one SP in height.
      pMRI is useful for investigating the accuracy of SP palpation in positions
      relevant to clinical and research practice.

PMID- 23134686
TI  - Increasing the use of preventative health services to promote healthy eating,
      physical activity and weight management: the acceptability and potential
      effectiveness of a proactive telemarketing approach.
AB  - BACKGROUND: Telephone based interventions are effective in promoting health
      behaviours. The use of telephone based support services to promote healthy
      eating, activity or weight loss, however, are currently under-utilised. The aim
      of this study was to assess the acceptability and potential effectiveness of a
      telemarketing approach in increasing community use of proactive services to
      encourage healthy eating, physical activity and weight loss. METHODS: The study
      employed a cross sectional design. Eligible consenting participants completed a
      15 minute telephone survey conducted by trained telephone interviewers using
      computer assisted telephone interviewing technology. RESULTS: Overall, 87% of
      participants considered it acceptable for a health service to contact people by
      telephone to offer assistance to help them lose weight, eat healthily or be more
      physically active. Among participants with inadequate fruit and vegetable intake,
      physical activity or who were overweight, 64%, 54% and 61% respectively reported
      that they would use one or more of the proactive support services offered.
      Females and those from non -English speaking households who did not eat
      sufficient serves were significantly more likely to report that they would use
      support services. CONCLUSIONS: The findings suggest that proactive telemarketing
      of health services to facilitate healthy eating, physical activity or weight loss
      is considered highly acceptable and may be effective in encouraging service use
      by more than half of all adults with these behavioural risks.

PMID- 23134684
TI  - Phosphotyrosine recognition domains: the typical, the atypical and the versatile.
AB  - SH2 domains are long known prominent players in the field of phosphotyrosine
      recognition within signaling protein networks. However, over the years they have
      been joined by an increasing number of other protein domain families that can, at
      least with some of their members, also recognise pTyr residues in a sequence
      specific context. This superfamily of pTyr recognition modules, which includes
      substantial fractions of the PTB domains, as well as much smaller, or even single
      member fractions like the HYB domain, the PKCdelta and PKCtheta C2 domains and
      RKIP, represents a fascinating, medically relevant and hence intensely studied
      part of the cellular signaling architecture of metazoans. Protein tyrosine
      phosphorylation clearly serves a plethora of functions and pTyr recognition
      domains are used in a similarly wide range of interaction modes, which encompass,
      for example, partner protein switching, tandem recognition functionalities and
      the interaction with catalytically active protein domains. If looked upon closely
      enough, virtually no pTyr recognition and regulation event is an exact mirror
      image of another one in the same cell. Thus, the more we learn about the biology
      and ultrastructural details of pTyr recognition domains, the more does it become
      apparent that nature cleverly combines and varies a few basic principles to
      generate a sheer endless number of sophisticated and highly effective
      recognition/regulation events that are, under normal conditions, elegantly
      orchestrated in time and space. This knowledge is also valuable when exploring
      pTyr reader domains as diagnostic tools, drug targets or therapeutic reagents to
      combat human diseases.

PMID- 23134687
TI  - The Yak genome database: an integrative database for studying yak biology and
      high-altitude adaption.
AB  - BACKGROUND: The yak (Bos grunniens) is a long-haired bovine that lives at high
      altitudes and is an important source of milk, meat, fiber and fuel. The recent
      sequencing, assembly and annotation of its genome are expected to further our
      understanding of the means by which it has adapted to life at high altitudes and
      its ecologically important traits. DESCRIPTION: The Yak Genome Database (YGD) is
      an internet-based resource that provides access to genomic sequence data and
      predicted functional information concerning the genes and proteins of Bos
      grunniens. The curated data stored in the YGD includes genome sequences,
      predicted genes and associated annotations, non-coding RNA sequences,
      transposable elements, single nucleotide variants, and three-way whole-genome
      alignments between human, cattle and yak. YGD offers useful searching and data
      mining tools, including the ability to search for genes by name or using function
      keywords as well as GBrowse genome browsers and/or BLAST servers, which can be
      used to visualize genome regions and identify similar sequences. Sequence data
      from the YGD can also be downloaded to perform local searches. CONCLUSIONS: A new
      yak genome database (YGD) has been developed to facilitate studies on high
      altitude adaption and bovine genomics. The database will be continuously updated
      to incorporate new information such as transcriptome data and population
      resequencing data. The YGD can be accessed at http://me.lzu.edu.cn/yak.

PMID- 23134688
TI  - CRYSTMAS study adds to concerns about renal safety and increased mortality in
      sepsis patients.

PMID- 23134689
TI  - A nonparametric Bayesian approach for clustering bisulfate-based DNA methylation
      profiles.
AB  - BACKGROUND: DNA methylation occurs in the context of a CpG dinucleotide. It is an
      important epigenetic modification, which can be inherited through cell division.
      The two major types of methylation include hypomethylation and hypermethylation.
      Unique methylation patterns have been shown to exist in diseases including
      various types of cancer. DNA methylation analysis promises to become a powerful
      tool in cancer diagnosis, treatment and prognostication. Large-scale methylation
      arrays are now available for studying methylation genome-wide. The Illumina
      methylation platform simultaneously measures cytosine methylation at more than
      1500 CpG sites associated with over 800 cancer-related genes. Cluster analysis is
      often used to identify DNA methylation subgroups for prognosis and diagnosis.
      However, due to the unique non-Gaussian characteristics, traditional clustering
      methods may not be appropriate for DNA and methylation data, and the
      determination of optimal cluster number is still problematic. METHOD: A Dirichlet
      process beta mixture model (DPBMM) is proposed that models the DNA methylation
      expressions as an infinite number of beta mixture distribution. The model allows
      automatic learning of the relevant parameters such as the cluster mixing
      proportion, the parameters of beta distribution for each cluster, and especially
      the number of potential clusters. Since the model is high dimensional and
      analytically intractable, we proposed a Gibbs sampling "no-gaps" solution for
      computing the posterior distributions, hence the estimates of the parameters.
      RESULT: The proposed algorithm was tested on simulated data as well as
      methylation data from 55 Glioblastoma multiform (GBM) brain tissue samples. To
      reduce the computational burden due to the high data dimensionality, a dimension
      reduction method is adopted. The two GBM clusters yielded by DPBMM are based on
      data of different number of loci (P-value < 0.1), while hierarchical clustering
      cannot yield statistically significant clusters.

PMID- 23134690
TI  - A longitudinal assessment of alcohol intake and incident depression: the SUN
      project.
AB  - BACKGROUND: Longitudinal studies assessing the long-term association between
      alcohol intake and depression are scarce. The type of beverage may also be
      important. Therefore we aimed to prospectively evaluate the influence of alcohol
      intake on incident depression in a Mediterranean cohort. METHODS: We assessed
      13,619 university graduates (mean age: 38 years, 42% men) participating in a
      Spanish prospective epidemiological cohort (the SUN Project), initially free of
      depression. They were recruited between 1999-2008 and biennially followed-up
      during 2001-2010. At baseline, a 136-item validated food-frequency questionnaire
      was used to assess alcohol intake. Wine was the preferred beverage. Participants
      were classified as incident cases of depression if they reported a new clinical
      diagnosis of depression by a physician and/or initiated the use of antidepressant
      drugs. Cox regression and restricted cubic splines analyses were performed over
      82,926 person-years. RESULTS: Only among women, an U-shaped relationship between
      total alcohol intake and depression risk was found (P=0.01). Moderate alcohol
      intake (5-15 g/day) was associated with lower risk (Hazard Ratio: 0.62; 95%
      Confidence Interval: 0.43-0.89). No association was apparent for higher intakes
      of alcohol or for any specific type of alcoholic beverage. CONCLUSIONS: Moderate
      alcohol intake might protect against depression among women. Further confirmatory
      studies are needed.

PMID- 23134691
TI  - Performance of SOAR (systolic blood pressure, oxygenation, age and respiratory
      rate) scoring criteria in community-acquired pneumonia: a prospective multi
      centre study.
AB  - BACKGROUND: severity assessment in community-acquired pneumonia (CAP) is
      important as it is associated with significant mortality. In this study, we
      compared a previously suggested severity assessment rule for CAP- SOAR (systolic
      blood pressure, oxygenation, age and respiratory rate)- against the CURB-65
      criteria. METHODS: we conducted a prospective study in three hospitals in Norfolk
      and Suffolk, UK. Consecutive patients with CAP were scored for severity with CURB
      65 (n = 190), and SOAR (when there was sufficient information, n = 112).
      Mortality data was collected at 6 weeks. RESULTS: there were 100 males (53%). The
      age range was 18-101 years (mean 72 years, median 76 years). Sixty-five (34%) had
      severe pneumonia by CURB-65, and 56 patients out of 112 (50%) had severe
      pneumonia by SOAR. Patients with severe CAP were significantly more likely to be
      older, female, and to have higher urea levels and a lower PaO(2):FiO(2) ratio on
      admission. There were a total of 54 deaths during follow-up (33 of these in the
      SOAR-categorised group). There were 32 deaths (50%) in the severe and 22 deaths
      (18%) in the non-severe groups by CURB-65. There were 23 deaths (70%) in the
      severe and 22 deaths (30%) in the non-severe groups by SOAR. For CURB-65,
      sensitivity, specificity, positive and negative predictive values were 60.6,
      72.2, 47.6 and 81.4%. For SOAR, the respective values were 69.7%, 58.2, 41.1 and
      82.1%. CONCLUSION: SOAR had demonstrably better sensitivity, but lower
      specificity compared with CURB-65 in this patient cohort. SOAR might be more
      suitable for assessing disease severity as an alternative or adjunct to CURB-65,
      particularly in the elderly.

PMID- 23134692
TI  - Root transcriptional responses of two melon genotypes with contrasting resistance
      to Monosporascus cannonballus (Pollack et Uecker) infection.
AB  - BACKGROUND: Monosporascus cannonballus is the main causal agent of melon vine
      decline disease. Several studies have been carried out mainly focused on the
      study of the penetration of this pathogen into melon roots, the evaluation of
      symptoms severity on infected roots, and screening assays for breeding programs.
      However, a detailed molecular view on the early interaction between M.
      cannonballus and melon roots in either susceptible or resistant genotypes is
      lacking. In the present study, we used a melon oligo-based microarray to
      investigate the gene expression responses of two melon genotypes, Cucumis melo
      'Piel de sapo' ('PS') and C. melo 'Pat 81', with contrasting resistance to the
      disease. This study was carried out at 1 and 3 days after infection (DPI) by M.
      cannonballus. RESULTS: Our results indicate a dissimilar behavior of the
      susceptible vs. the resistant genotypes from 1 to 3 DPI. 'PS' responded with a
      more rapid infection response than 'Pat 81' at 1 DPI. At 3 DPI the total number
      of differentially expressed genes identified in 'PS' declined from 451 to 359,
      while the total number of differentially expressed transcripts in 'Pat 81'
      increased from 187 to 849. Several deregulated transcripts coded for components
      of Ca2+ and jasmonic acid (JA) signalling pathways, as well as for other proteins
      related to defence mechanisms. Transcriptional differences in the activation of
      the JA-mediated response in 'Pat 81' compared to 'PS' suggested that JA response
      might be partially responsible for their observed differences in resistance.
      CONCLUSIONS: As a result of this study we have identified for the first time a
      set of candidate genes involved in the root response to the infection of the
      pathogen causing melon vine decline. This information is useful for understanding
      the disease progression and resistance mechanisms few days after inoculation.

PMID- 23134693
TI  - A simplified approach to true molar intrusion.
AB  - BACKGROUND: Orthodontic management of anterior open bites is a demanding task for
      orthodontists. Molar intrusion as a primary means of open bite correction entails
      the need for appropriate anchorage. Orthodontic mini implants can provide the
      required mechanical support. The suggested procedure aims to reduce the risk of
      complications such as root damage or soft tissue irritations while minimizing
      overall complexity. METHODS: Three female patients aged 14, 18 and 19 years who
      decided against a surgical correction were treated with a device consisting of
      mini implants in the palatal slope, a palatal bar and intrusion cantilevers.
      RESULTS: In all three patients, an open bite reduction of more than a millimeter
      occurred within four months. An anterior overbite of 2 mm or more could be
      established within 6 to 9 months. CONCLUSIONS: The method presented in this
      article enables the practitioner to use mini implants in an easily accessible
      insertion site. A lab-side procedure is optional but not required.

PMID- 23134694
TI  - The host response to infection: advancing a novel diagnostic paradigm.
AB  - Capturing the host response by using genomic technologies such as transcriptional
      profiling provides a new paradigm for classifying and diagnosing infectious
      disease and for potentially distinguishing infection from other causes of serious
      respiratory illness. This strategy has been used to define a blood-based RNA
      signature as a classifier for pandemic H1N1 influenza infection that is distinct
      from bacterial pneumonia and other inflammatory causes of respiratory disease. To
      realize the full potential of this approach as a diagnostic test will require
      additional independent validation of the results and studies to examine the
      specificity of this signature for viral versus bacterial infection or co
      infection. 

PMID- 23134695
TI  - Neuro psychiatry 1943: the role of documentary film in the dissemination of
      medical knowledge and promotion of the U.K. psychiatric profession.
AB  - In 1943, Basil Wright produced a documentary film about the treatment of
      servicemen and civilians with psychological disorders at Mill Hill Emergency
      Medical Service Hospital. Funded by the Ministry of Information, Neuro Psychiatry
      was shot to convince influential clinicians and policy makers in North America
      that the British had developed expertise in the management of psychiatric
      casualties. By emphasizing novel and apparently effective interventions and
      excluding severe or intractable cases from the film, Wright encouraged an
      optimistic sense of achievement. Filmed at a time when victory was considered an
      eventual outcome, the picture presented a health service to which all had access
      without charge. Children and unemployed women, two groups excluded under the 1911
      National Insurance Act, had been required to pay for healthcare in the prewar
      period and were shown receiving free treatment from the Emergency Medical
      Service. However, the therapeutic optimism presented in the film proved
      premature. Most U.K. battle casualties arose in the latter half of the conflict
      and follow-up studies failed to confirm the positive outcome statistics reported
      in the film. Aubrey Lewis, clinical director of the hospital, criticized research
      projects conducted at Mill Hill for a lack of rigor. The cinematographic skills
      of Wright and director Michael Hankinson, together with their reformist agenda,
      created a clinical presentation that emphasized achievements without
      acknowledging the limitations not only of the therapies offered by doctors but
      also the resources available to a nation at war. 

PMID- 23134696
TI  - Diagnosis of paediatric tuberculosis: the culture conundrum.

PMID- 23134697
TI  - Assessment of the Xpert MTB/RIF assay for diagnosis of tuberculosis with gastric
      lavage aspirates in children in sub-Saharan Africa: a prospective descriptive
      study.
AB  - BACKGROUND: Rapid and accurate diagnosis of pulmonary tuberculosis in children
      remains challenging because of difficulties in obtaining sputum samples and the
      paucibacillary nature of the disease. The Xpert MTB/RIF assay is useful for rapid
      diagnosis of childhood tuberculosis with sputum and nasopharyngeal samples. We
      assessed this assay for the detection of tuberculosis and multidrug resistant
      (MDR) tuberculosis with gastric lavage aspirate (GLA) samples in children
      admitted to hospital. METHODS: We did a prospective study to assess the
      sensitivity and specificity of the Xpert MTB/RIF assay with GLA samples for the
      detection of pulmonary tuberculosis and MDR tuberculosis in new paediatric
      inpatient admissions at the University Teaching Hospital, Lusaka, Zambia.
      Children aged 15 years or younger were recruited between June, 2011, and May,
      2012. GLA and sputum were analysed by standard smear-microscopy, mycobacterial
      growth indicator tube (MGIT) culture, MGIT drug-susceptibility testing, and the
      Xpert MTB/RIF assay. Sensitivity of the Xpert MTB/RIF assay was assessed with the
      Pearson chi(2) or Fishers exact test. FINDINGS: Of 930 children, 142 produced
      sputum and GLA was obtained from 788 non-sputum producers. Culture-positive
      tuberculosis was identified in 58 (6.2%) of 930 children: ten from sputum
      producers and 48 from GLA of non-sputum producers. The sensitivity and
      specificity of the Xpert MTB/RIF assay were similar: sensitivity was 68.8% (95%
      CI 53.6-80.9) for GLA versus 90.0% (54.1-99.5; p=0.1649) for sputum samples;
      specificity was 99.3% (98.3-99.8) for GLA and 98.5% (94.1-99.7; p=0.2871) for
      sputum samples. The Xpert MTB/RIF assay detected an extra 28 tuberculosis cases
      compared with smear microscopy and was significantly more sensitive than smear
      microscopy for both sputum (90.0% [54.1-99.5] vs 30.0% [8.1-64.6], p=0.01) and
      GLA (68.8% [53.6-80.9] vs 25.0% [14.1-40.0], p<0.0001). The assay load did not
      differ significantly by sample type (p=0.791). 22 children were infected with HIV
      and tuberculosis and significant differences in assay performance could not be
      detected when stratifying by HIV status for either sample type. The Xpert MTB/RIF
      assay detected rifampicin resistance in three GLA samples: two confirmed as MDR
      tuberculosis and one false positive. INTERPRETATION: Analyses of GLA samples with
      the Xpert MTB/RIF assay is a sensitive and specific method for rapid diagnosis of
      pulmonary tuberculosis in children who cannot produce sputum. The single site
      nature of our study invites caution. FUNDING: European Commission, European
      Developing Countries Clinical Trials Partnership, and UBS Optimus Foundation.

PMID- 23134698
TI  - Reporting guidelines for modelling studies.
AB  - BACKGROUND: Modelling studies are used widely to help inform decisions about
      health care and policy and their use is increasing. However, in order for
      modelling to gain strength as a tool for health policy, it is critical that key
      model factors are transparent so that users of models can have a clear
      understanding of the model and its limitations.Reporting guidelines are evidence
      based tools that specify minimum criteria for authors to report their research
      such that readers can both critically appraise and interpret study findings. This
      study was conducted to determine whether there is an unmet need for population
      modelling reporting guidelines. METHODS: We conducted a review of the literature
      to identify: 1) guidance for reporting population modelling studies; and, 2)
      evidence on the quality of reporting of population modelling studies. Guidance
      for reporting was analysed using a thematic approach and the data was summarised
      as frequencies. Evidence on the quality of reporting was reviewed and summarized
      descriptively. RESULTS: There were no guidelines that specifically addressed the
      reporting of population modelling studies. We identified a number of reporting
      guidelines for economic evaluation studies, some of which had sections that were
      relevant population modelling studies. Amongst seven relevant records, we
      identified 69 quality criteria that have distinct reporting characteristics. We
      identified two papers that addressed reporting practices of modelling studies.
      Overall, with the exception of describing the data used for calibration, there
      was little consistency in reporting. CONCLUSIONS: While numerous guidelines exist
      for developing and evaluating health technology assessment and economic
      evaluation models, which by extension could be applicable to population modelling
      studies, there is variation in their comprehensiveness and in the consistency of
      reporting these methods. Population modelling studies may be an area which would
      benefit from the development of a reporting guideline.

PMID- 23134699
TI  - Ganglioside GD2-specific trifunctional surrogate antibody Surek demonstrates
      therapeutic activity in a mouse melanoma model.
AB  - BACKGROUND: Trifunctional bispecific antibodies (trAb) are a special class of
      bispecific molecules recruiting and activating T cells and accessory immune cells
      simultaneously at the targeted tumor. The new trAb Ektomab that targets the
      melanoma-associated ganglioside antigen GD2 and the signaling molecule human CD3
      (hCD3) on T cells demonstrated potent T-cell activation and tumor cell
      destruction in vitro. However, the relatively low affinity for the GD2 antigen
      raised the question of its therapeutic capability. To further evaluate its
      efficacy in vivo it was necessary to establish a mouse model. METHODS: We
      generated the surrogate trAb Surek, which possesses the identical anti-GD2
      binding arm as Ektomab, but targets mouse CD3 (mCD3) instead of hCD3, and
      evaluated its chemical and functional quality as a therapeutic antibody
      homologue. The therapeutic and immunizing potential of Surek was investigated
      using B78-D14, a B16 melanoma transfected with GD2 and GD3 synthases and showing
      strong GD2 surface expression. The induction of tumor-associated and autoreactive
      antibodies was evaluated. RESULTS: Despite its low affinity of approximately
      10(7) M(-1) for GD2, Surek exerted efficient tumor cell destruction in vitro at
      an EC(50) of 70 ng/ml [0.47 nM]. Furthermore, Surek showed strong therapeutic
      efficacy in a dose-dependent manner and is superior to the parental GD2 mono
      specific antibody, while the use of a control trAb with irrelevant target
      specificity had no effect. The therapeutic activity of Surek was strictly
      dependent on CD4(+) and CD8(+) T cells, and cured mice developed a long-term
      memory response against a second challenge even with GD2-negative B16 melanoma
      cells. Moreover, tumor protection was associated with humoral immune responses
      dominated by IgG2a and IgG3 tumor-reactive antibodies indicating a Th1-biased
      immune response. Autoreactive antibodies against the GD2 target antigen were not
      induced. CONCLUSION: Our data suggest that Surek revealed strong tumor
      elimination and anti-tumor immunization capabilities. The results warrant further
      clinical development of the human therapeutic equivalent antibody Ektomab.

PMID- 23134700
TI  - Mathematical modeling and stability analysis of macrophage activation in left
      ventricular remodeling post-myocardial infarction.
AB  - BACKGROUND: About 6 million Americans suffer from heart failure and 70% of heart
      failure cases are caused by myocardial infarction (MI). Following myocardial
      infarction, increased cytokines induce two major types of macrophages:
      classically activated macrophages which contribute to extracellular matrix
      destruction and alternatively activated macrophages which contribute to
      extracellular matrix construction. Though experimental results have shown the
      transitions between these two types of macrophages, little is known about the
      dynamic progression of macrophages activation. Therefore, the objective of this
      study is to analyze macrophage activation patterns post-MI. RESULTS: We have
      collected experimental data from adult C57 mice and built a framework to
      represent the regulatory relationships among cytokines and macrophages. A set of
      differential equations were established to characterize the regulatory
      relationships for macrophage activation in the left ventricle post-MI based on
      the physical chemistry laws. We further validated the mathematical model by
      comparing our computational results with experimental results reported in the
      literature. By applying Lyaponuv stability analysis, the established mathematical
      model demonstrated global stability in homeostasis situation and bounded response
      to myocardial infarction. CONCLUSIONS: We have established and validated a
      mathematical model for macrophage activation post-MI. The stability analysis
      provided a possible strategy to intervene the balance of classically and
      alternatively activated macrophages in this study. The results will lay a strong
      foundation to understand the mechanisms of left ventricular remodelling post-MI.

PMID- 23134701
TI  - Public health interventions in midwifery: a systematic review of systematic
      reviews.
AB  - BACKGROUND: Maternity care providers, particularly midwives, have a window of
      opportunity to influence pregnant women about positive health choices. This aim
      of this paper is to identify evidence of effective public health interventions
      from good quality systematic reviews that could be conducted by midwives.
      METHODS: Relevant databases including MEDLINE, Pubmed, EBSCO, CRD, MIDIRS, Web of
      Science, The Cochrane Library and Econlit were searched to identify systematic
      reviews in October 2010. Quality assessment of all reviews was conducted.
      RESULTS: Thirty-six good quality systematic reviews were identified which
      reported on effective interventions. The reviews were conducted on a diverse
      range of interventions across the reproductive continuum and were categorised
      under: screening; supplementation; support; education; mental health; birthing
      environment; clinical care in labour and breast feeding. The scope and strength
      of the review findings are discussed in relation to current practice. A logic
      model was developed to provide an overarching framework of midwifery public
      health roles to inform research policy and practice. CONCLUSIONS: This review
      provides a broad scope of high quality systematic review evidence and
      definitively highlights the challenge of knowledge transfer from research into
      practice. The review also identified gaps in knowledge around the impact of core
      midwifery practice on public health outcomes and the value of this contribution.
      This review provides evidence for researchers and funders as to the gaps in
      current knowledge and should be used to inform the strategic direction of the
      role of midwifery in public health in policy and practice.

PMID- 23134702
TI  - Optimizing positive end-expiratory pressure by oscillatory mechanics minimizes
      tidal recruitment and distension: an experimental study in a lavage model of lung
      injury.
AB  - INTRODUCTION: It is well established that during mechanical ventilation of
      patients with acute respiratory distress syndrome cyclic
      recruitment/derecruitment and overdistension are potentially injurious for lung
      tissues. We evaluated whether the forced oscillation technique (FOT) could be
      used to guide the ventilator settings in order to minimize cyclic lung
      recruitment/derecruitment and cyclic mechanical stress in an experimental model
      of acute lung injury. METHODS: We studied six pigs in which lung injury was
      induced by bronchoalveolar lavage. The animals were ventilated with a tidal
      volume of 6 ml/kg. Forced oscillations at 5 Hz were superimposed on the
      ventilation waveform. Pressure and flow were measured at the tip and at the inlet
      of the endotracheal tube respectively. Respiratory system reactance (Xrs) was
      computed from the pressure and flow signals and expressed in terms of oscillatory
      elastance (EX5). Positive end-expiratory pressure (PEEP) was increased from 0 to
      24 cm H2O in steps of 4 cm H2O and subsequently decreased from 24 to 0 in steps
      of 2 cm H2O. At each PEEP step CT scans and EX5 were assessed at end-expiration
      and end-inspiration. RESULTS: During deflation the relationship between both end
      expiratory and end-inspiratory EX5 and PEEP was a U-shaped curve with minimum
      values at PEEP = 13.4 +/- 1.0 cm H2O (mean +/- SD) and 13.0 +/- 1.0 cm H2O
      respectively. EX5 was always higher at end-inspiration than at end-expiration,
      the difference between the average curves being minimal at 12 cm H2O. At this
      PEEP level, CT did not show any substantial sign of intra-tidal
      recruitment/derecruitment or expiratory lung collapse. CONCLUSIONS: Using FOT it
      was possible to measure EX5 both at end-expiration and at end-inspiration. The
      optimal PEEP strategy based on end-expiratory EX5 minimized intra-tidal
      recruitment/derecruitment as assessed by CT, and the concurrent attenuation of
      intra-tidal variations of EX5 suggests that it may also minimize tidal mechanical
      stress.

PMID- 23134703
TI  - Low MRSA prevalence in horses at farm level.
AB  - BACKGROUND: In Europe, methicillin-resistant Staphylococcus aureus (MRSA)
      belonging to the clonal complex (CC) 398 has become an important pathogen in
      horses, circulating in equine clinics and causing both colonization and
      infection. Whether equine MRSA is bound to hospitals or can also circulate in the
      general horse population is currently unknown. This study, therefore, reports the
      nasal and perianal MRSA screening of 189 horses on 10 farms in a suspected high
      prevalence region (East- and West-Flanders, Belgium). RESULTS: Only one horse
      (0.53%) from one farm (10%) tested positive in the nose. It carried a spa type
      t011-SCCmecV isolate, resistant to beta-lactams and tetracycline, which is
      typical for livestock-associated MRSA CC398. CONCLUSION: In the region tested
      here, horses on horse farms seem unlikely to substantially contribute to the
      large animal associated ST398 MRSA reservoir present at intensive animal
      production units.

PMID- 23134704
TI  - An ultra-short screening version of the Recalled Parental Rearing Behavior
      questionnaire (FEE-US) and its factor structure in a representative German
      sample.
AB  - BACKGROUND: The Recalled Parental Rearing Behavior questionnaire (FEE, [1,2])
      assesses perceived parental rearing behavior separately for each parent. An ultra
      short screening version (FEE-US) with the same three scales each for the mother
      and the father is reported and factor-analytically validated. METHODS: N = 4,640
      subjects aged 14 to 92 (M = 48.4 years) were selected by the random-route
      sampling method. The ultra-short questionnaire version was derived from the long
      version through item and factor analyses. In a confirmatory factor analysis
      framework, the hypothesized three-factorial structure was fitted to the empirical
      data and tested for measurement invariance, differential item functioning, item
      discriminability, and convergent and discriminant factorial validity. Effects of
      gender or age were assessed using MANOVAs. RESULTS: The a-priori hypothesized
      model resulted in mostly adequate overall fit. Neither gender nor age group
      yielded considerable effects on the factor structure, but had small effects on
      means of raw score sums. Factorial validities could be confirmed. Scale sums are
      well-suited to rank respondents along the respective latent dimension.
      CONCLUSION: The structure of the long version with the factors Rejection &
      Punishment, Emotional Warmth, and Control & Overprotection could be replicated
      for both father and mother items in the ultra-short screening version using
      confirmatory factor analyses. These results indicate that the ultra-short
      screening version is a time-saving and promising screening instrument for
      research settings and in individual counseling. However, the shortened scales do
      not necessarily represent the full spectrum covered by the full-scale dimensions.

PMID- 23134705
TI  - Selected articles from the IEEE International Workshop on Genomic Signal
      Processing and Statistics (GENSIPS'2011).

PMID- 23134706
TI  - Opportunities and challenges of disease biomarkers: a new section in the Journal
      of Translational Medicine.

PMID- 23134707
TI  - Integrative genome-wide chromatin signature analysis using finite mixture models.
AB  - Regulation of gene expression has been shown to involve not only the binding of
      transcription factor at target gene promoters but also the characterization of
      histone around which DNA is wrapped around. Some histone modification, for
      example di-methylated histone H3 at lysine 4 (H3K4me2), has been shown to bind to
      promoters and activate target genes. However, no clear pattern has been shown to
      predict human promoters. This paper proposed a novel quantitative approach to
      characterize patterns of promoter regions and predict novel and alternative
      promoters. We utilized high-throughput data generated using chromatin
      immunoprecipitation methods followed by massively parallel sequencing (ChIP-seq)
      technology on RNA Polymerase II (Pol-II) and H3K4me2. Common patterns of promoter
      regions are modeled using a mixture model involving double-exponential and
      uniform distributions. The fitted model obtained were then used to search for
      regions displaying similar patterns over the entire genome to find novel and
      alternative promoters. Regions with high correlations with the common patterns
      are identified as putative novel promoters. We used this proposed algorithm, RNA
      seq data and several transcripts databases to find alternative promoters in MCF7
      (normal breast cancer) cell line. We found 7,235 high-confidence regions that
      display the identified promoter patterns. Of these, 4,167 regions (58%) can be
      mapped to RefSeq regions. 2,444 regions are in a gene body or overlap with
      transcripts (non-coding RNAs, ESTs, and transcripts that are predicted by RNA-seq
      data). Some of these maybe potential alternative promoters. We also found 193
      regions that map to enhancer regions (represented by androgen and estrogen
      receptor binding sites) and other regulatory regions such as CTCF (CCCTC binding
      factor) and CpG island. Around 5% (431 regions) of these correlated regions do
      not overlap with any transcripts or regulatory regions suggesting that these
      might be potential new promoters or markers for other annotation which are
      currently undiscovered.

PMID- 23134708
TI  - Incomplete punctal canalisation: the external and internal punctal membranes.
      Outcomes of membranotomy and adjunctive procedures.
AB  - AIMS: To study the clinical and diagnostic profile of punctal dysgenesis with
      membranes, to classify and correlate the membranes clinicopathologically and
      study the outcomes of membranotomy. METHODS: A prospective interventional study
      involving 55 dysgenetic puncta of 22 consecutive patients seen between July 2008
      ansd December 2011. Data collected include demographics, clinical presentation,
      laterality, age at presentation, duration of symptoms, slit lamp examination,
      punctal profiles, types of membranes, associated lacrimal anomalies, management
      and outcomes. All the patients underwent membranotomy, after which the puncta
      were assessed for adequacy of the opening, the canaliculi were assessed with
      probes and irrigation was done to assess the patency of the lacrimal system. A
      minimal follow-up of 6 months was taken for final analysis. Primary outcome
      measures included were anatomical patency on irrigation and relief from epiphora
      assessed subjectively and also objectively by a dye disappearance test. RESULTS:
      The patients included 11 males and 11 females, with a mean age of 82.4 months
      (range 5-264 months) at presentation. Bilateral punctal involvement was seen in
      59% (13/22) and all the four puncta were affected in 31.8% (7/22) of the
      patients. Epiphora was the most common complaint noted in 95% (21/22), and the
      symptoms were noticed since birth in 68.1% (15/22). External membranes over the
      puncta were noted in 86.4% (19/22) and internal punctal membranes in 13.6% (3/22)
      of patients. All the patients underwent membranotomy, however additional
      procedures like probing was done in 13.6% (3/22), mini-monoka intubation in 9.1%
      (2/22), Crawford's bicanalicular intubation in 9.1% (2/22) and
      dacryocystorhinostomy in 4.5% (1/22). Uniformly, the punctal membranes on
      histopathological examination were fibrovascular membranes. The anatomical
      patency was 100% and relief from symptoms was seen in 91% (20/22) of the
      patients. CONCLUSIONS:  This study presents the largest series to date (n=55
      puncta) exclusively on punctal dysgenesis with membranes and, for the first time,
      has shown the clinicopathological correlation of these membranes. Incomplete
      punctal canalisation is probably a better term and this study could be the
      starting point for further exploration into the etiopathogenesis and genetics of
      this intriguing congenital disorder.

PMID- 23134709
TI  - Visual acuity after Gamma-Knife radiosurgery of choroidal melanomas.
AB  - BACKGROUND/AIMS: To report on conservation of visual acuity after Gamma-Knife
      radiosurgery of choroidal melanoma. METHODS: A total of 189 patients with
      choroidal melanoma were treated with Gamma-Knife stereotactic single-fraction
      radiosurgery at a single institution between June 1992 and May 2010. The main
      outcome measure of our retrospective analysis was conservation of pretreatment
      visual acuity of 20/40 or better, 20/200 or better and counting fingers (CF) or
      better, over time of follow-up. Patient, tumour and treatment parameters were
      evaluated as potential risk factors for visual loss. RESULTS: Five years after
      treatment, the actuarial probability of keeping visual acuity better than 20/40,
      20/200 and CF was 13%, 14% and 36%, respectively. The majority of patients
      (84.7%) encountered a deterioration of vision after treatment. The most important
      risk factors for visual loss were tumour height, longest basal diameter, distance
      to the optic disk and/or foveola, and retinal detachment before treatment.
      Treatment dose, and patient characteristics (age, sex, concurrent systemic
      diseases) were less important. Local tumour control rate was 94.4% after a median
      follow-up of 39.5 months. CONCLUSIONS: Visual outcome after single-fraction Gamma
      Knife radiotherapy is comparable with linear accelerator (LINAC) based
      fractionated stereotactic radiotherapy, inferior to proton beam radiotherapy, and
      depends primarily on tumour size, location and pre-existing retinal detachment.

PMID- 23134710
TI  - Medial rectus Faden operations with or without recession for partially
      accommodative esotropia associated with a high accommodative convergence to
      accommodation ratio.
AB  - AIMS: To evaluate the results of Faden operations on the medial rectus (MR)
      muscles with or without recession for the treatment of partially accommodative
      esotropia associated with a high accommodative convergence to accommodation (AC :
      A) ratio and to determine whether there was a decrease in the effects of
      posterior fixation over time. METHODS: In this retrospective study, 108 of 473
      patients who underwent surgery for partially accommodative esotropia with a high
      AC : A ratio received Faden operations on both MR muscles, and 365 received
      symmetric MR muscle recessions combined with a Faden operation. RESULTS: For the
      Faden operation, a satisfactory outcome of 76.9% at 1 month postoperation,
      decreased to 71.3% by the final follow-up visit (mean 4.8 years). A moderate
      positive correlation was observed between the increase in the postoperative near
      deviation and postoperative time. For the Faden operations combined with MR
      recession, a satisfactory outcome of 78.9% at 1 month post-operation, decreased
      to 78.4% by the final follow-up visit. CONCLUSION: A Faden operation of the MR
      muscles with or without recession is an effective surgical option for treating
      partially accommodative esotropia associated with a high AC : A ratio. For Faden
      operations of the MR muscles without recession, the effects of the posterior
      fixation decline over time.

PMID- 23134711
TI  - Predicting death or major neurodevelopmental disability in extremely preterm
      infants born in Australia.
AB  - BACKGROUND: The aim of this study was to determine if the National Institute of
      Child Health and Human Development (NICHD) calculator, designed to predict
      mortality or neurosensory disability in infants 22-25 weeks' gestation, was valid
      for contemporary Australian infants. METHOD: Outcome data at 2 years of age for
      114 infants who were liveborn in Victoria, Australia, in 2005, between 22 and 25
      completed weeks' gestation, weighing 401-1000 g at birth, and free of lethal
      anomalies, were entered into the NICHD online calculator. Predicted outcomes were
      then compared with the actual outcomes. RESULTS: Of the 114 infants, 99 (87%)
      were inborn and 15 (13%) were outborn. The overall prediction of death for inborn
      infants was 47.1% compared with the actual death rate to 2 years of age of 49.5%.
      The area under the curve (AUC) was 0.803 (95% CI 0.718 to 0.888; p<0.001) for
      mortality, comparable with the AUC for the NICHD study (AUC: 0.753; 95% CI 0.737
      to 0.769; p<0.001). The accuracy for predicting death was not as precise for
      outborn infants (AUC: 0.643; 95% CI 0.337 to 0.949; p=0.36). The calculator
      overestimated the combined outcome of death or survival with major disability at
      72.0%, compared with an actual rate of 60.5%. CONCLUSIONS: The NICHD outcome
      estimator was helpful in predicting mortality for inborn infants, 22-25 weeks'
      gestation, but was less precise for outborn infants. It overestimated the
      combined outcome of death or major disability in infants born in Victoria,
      Australia, in 2005.

PMID- 23134713
TI  - Subchronic hepatotoxicity evaluation of hydrazobenzene in Fischer 344 rats.
AB  - Male F344 rats were exposed to hydrazobenzene (HZB) by dietary feed at
      concentrations of 0, 5, 20, 80, 200, or 300 ppm for 5 days, 2 weeks, 4 weeks, or
      13 weeks duration. End points evaluated included clinical observations, body
      weights, liver weights, serum chemistry, blood HZB, gross pathology, and liver
      histopathology. There were no HZB exposure-related clinical signs of toxicity.
      During study weeks 8 through 13, body weight means in rats of the 300 ppm group
      were 6% lower compared to control rat means. Serum alkaline phosphatase
      concentrations were decreased in rats of the 300 ppm group at all time points.
      Relative (to body weight) liver weight increases were observed in rats of the 200
      and 300 ppm groups following 5 days (300 ppm only), 2 weeks, 4 weeks, and 13
      weeks of exposure. Following 13 weeks of exposure, microscopic findings in the
      liver were observed only in rats of the 200 and 300 ppm groups and consisted of
      hypertrophy, macrovesiculation, eosinophilic granular cytoplasm, and bile duct
      duplication. Blood HZB concentrations ranged from 0.002 to 0.006 ug/mL in rats of
      the 200 or 300 ppm groups. A no observed effect level of 80 ppm (4.80 mg/kg per
      d) was selected based on the observation of microscopic hepatocyte alterations at
      >=200 ppm HZB.

PMID- 23134714
TI  - The minipig as nonrodent species in toxicology--where are we now?
AB  - Over the past 3 decades minipigs have moved from being an obscure alternative to
      dogs and nonhuman primates to being a standard animal model in regulatory
      toxicity studies. This article covers the use of minipigs as a model in the
      context of nonclinical drug safety and provides an overview of the minipig's
      developmental history and relates minipigs to other animal species commonly used
      in toxicology; and the minipig's translational power is supported by 43 case
      studies of marketed drug products covered. Special focus is given to criteria for
      selecting minipigs in nonclinical programs supporting the development of new
      medicines; the use of swine in the assessment of food additives, agrochemicals,
      and pesticides; as well as a regulatory perspective on the use of minipigs in
      Food and Drug Administration (FDA)-regulated products. This article presents the
      main points conveyed at a symposium held at the 2010 American College of
      Toxicology meeting in Baltimore, Maryland.

PMID- 23134715
TI  - Fatal mephedrone intoxication--a case report.
AB  - A death caused by a new designer drug, 4-methylmethcathinone (mephedrone), is
      reported. Eight small plastic bags containing white powder were found in the
      jacket of a young dead male. Spot tests conducted by the police officer indicated
      the presence of 4-bromo-2,5-dimethoxyphenethylamine (2C-B) in the powders.
      Laboratory routine screening analyses of blood and vitreous humor did not reveal
      any positive results; therefore, 2C-B was excluded. Analysis of powders was
      conducted using gas chromatography-mass spectrometry and high-pressure liquid
      chromatography with diode array detection. The purity of mephedrone found in all
      powder samples was in the range of 80.4-87.3%. In connection with these findings,
      blood and vitreous humor samples were analyzed for mephedrone. Analyses were
      conducted using liquid chromatography-tandem mass spectrometry. Mephedrone was
      found in blood and vitreous humor at the concentrations of 5.5 and 7.1 ug/mL,
      respectively, revealing that this was a fatal mephedrone intoxication.

PMID- 23134716
TI  - Construct validation of patient global impression of severity (PGI-S) and
      improvement (PGI-I) questionnaires in the treatment of men with lower urinary
      tract symptoms secondary to benign prostatic hyperplasia.
AB  - BACKGROUND: Lower urinary tract symptoms (LUTS) in aging men are often associated
      with benign prostatic hyperplasia (BPH). While regulatory evaluations of
      treatment benefit require an assessment of specific symptoms, a simpler approach
      to measuring patients' perceptions of severity and symptom change may be
      particularly useful for clinical practice. The aim of this study was to provide
      evidence of the validity of the 1-item Patient Global Impression of Severity (PGI
      S) and Improvement (PGI-I) questionnaires for use as outcome measures in the
      treatment of BPH-LUTS. METHODS: This was a secondary analysis of data from 4
      randomized placebo-controlled 12-week trials evaluating tadalafil for the
      treatment of BPH-LUTS (N=1694). Visit 2 (V2 [beginning of a 4-week placebo lead
      in period]) and endpoint assessments included International Prostate Symptom
      Score (IPSS), IPSS Quality of Life Index (IPSS-QoL), BPH Impact Index (BII), and
      peak urine flow (Qmax). PGI-S was only administered at V2 and PGI-I only at
      endpoint. Associations between the PGI-S or the PGI-I and the other assessments
      were analyzed by calculating Spearman rank correlation coefficients and
      performing analysis of variance (ANOVA). RESULTS: Spearman correlation
      coefficients were 0.43, 0.43, 0.53, and -0.09, between the PGI-S and IPSS, IPSS
      QoL, BII, and Qmax baseline results (all P<0.001). Similar results were seen
      across race, ethnicity, and baseline severity (moderate LUTS versus severe LUTS).
      IPSS, IPSS-QoL, BII baseline scores (P <0.001) and Qmax values (P=0.003) were
      significantly different among the 4 PGI-S severity levels. Spearman correlation
      coefficients were 0.56, 0.53, 0.47 and -0.15 between the PGI-I and change in
      IPSS, IPSS-QoL, BII scores, and Qmax values from baseline to endpoint (all
      P<0.001). Similar results were seen across race, ethnicity, and baseline
      severity. Change in IPSS, IPSS-QoL, BII scores, and Qmax values (P<0.001) were
      significantly different among the PGI-I levels (i.e., patient perception of
      change in urinary symptoms). CONCLUSIONS: This study demonstrated patients'
      overall perceptions of their severity and change in BPH-LUTS can be captured in a
      way that is simple, valid, and easily administered in a research setting or
      clinical practice. Clinical parameters are weakly associated with patients'
      perception of urinary symptoms, emphasizing the importance of a patient-reported
      assessment in the evaluation of BPH-LUTS treatment benefit.

PMID- 23134717
TI  - Effectiveness of an antimicrobial treatment scheme in a confined glanders
      outbreak.
AB  - BACKGROUND: Glanders is a contagious and fatal zoonotic disease of solipeds
      caused by the Gram-negative bacterium Burkholderia (B.) mallei. Although
      regulations call for culling of diseased animals, certain situations e.g. wild
      life conservation, highly valuable breeding stock, could benefit from effective
      treatment schemes and post-exposure prophylaxis. RESULTS: Twenty three culture
      positive glanderous horses were successfully treated during a confined outbreak
      by applying a treatment protocol of 12 weeks duration based on the parenteral
      administration of enrofloxacin and trimethoprim plus sulfadiazine, followed by
      the oral administration of doxycycline. Induction of immunosupression in six
      randomly chosen horses after completion of treatment did not lead to
      recrudescence of disease. CONCLUSION: This study demonstrates that long term
      treatment of glanderous horses with a combination of various antibiotics seems to
      eliminate the agent from the organism. However, more studies are needed to test
      the effectiveness of this treatment regime on B. mallei strains from different
      endemic regions. Due to its cost and duration, this treatment can only be an
      option in certain situations and should not replace the current "testing and
      culling" policy, in conjunction with adequate compensation to prevent spreading
      of disease.

PMID- 23134718
TI  - Efficient calculation of steady state probability distribution for stochastic
      biochemical reaction network.
AB  - The Steady State (SS) probability distribution is an important quantity needed to
      characterize the steady state behavior of many stochastic biochemical networks.
      In this paper, we propose an efficient and accurate approach to calculating an
      approximate SS probability distribution from solution of the Chemical Master
      Equation (CME) under the assumption of the existence of a unique deterministic SS
      of the system. To find the approximate solution to the CME, a truncated state
      space representation is used to reduce the state-space of the system and
      translate it to a finite dimension. The subsequent ill-posed eigenvalue problem
      of a linear system for the finite state-space can be converted to a well-posed
      system of linear equations and solved. The proposed strategy yields efficient and
      accurate estimation of noise in stochastic biochemical systems. To demonstrate
      the approach, we applied the method to characterize the noise behavior of a set
      of biochemical networks of ligand-receptor interactions for Bone Morphogenetic
      Protein (BMP) signaling. We found that recruitment of type II receptors during
      the receptor oligomerization by itself doesn't not tend to lower noise in
      receptor signaling, but regulation by a secreted co-factor may provide a
      substantial improvement in signaling relative to noise. The steady state
      probability approximation method shortened the time necessary to calculate the
      probability distributions compared to earlier approaches, such as Gillespie's
      Stochastic Simulation Algorithm (SSA) while maintaining high accuracy.

PMID- 23134719
TI  - A comparative study of 22-channel water-perfusion system and solid-state system
      with 36-sensors in esophageal manometery.
AB  - BACKGROUND: To compare the characteristics between 22-channel water-perfusion
      manometry (WPM) and solid-state manometry (SSM) with 36 sensors of the pressure
      measurements, as well as patients' discomfort indices in nose and pharynx, the
      preparation and operation time of the manometry. METHODS: 12 volunteers were
      included in the study. Each of the volunteers underwent esophageal manometry by
      both 22-channel water-perfusion catheter (WPC) and solid-state catheter (SSC)
      with 36 sensors in random order, and separated by 30 min. The subjects gave a VAS
      score soon after each test. Non-parametric tests were used to analyze the
      differences and Bland-Altman plots were used to assess the consistency of the two
      systems. RESULTS: During the wet swallows, there were significant differences
      between the two systems in three measurements of location of lower esophageal
      sphincter (LES) upper margin (Z = -2.11, P = 0.035), LES relax ratio (Z = -2.20,
      P = 0.028) and IRP4s (Z = -2.05, P = 0.041). During the jelly pocket swallows,
      LES relax ratio measurements of the two systems showed significant differences (Z
      = -2.805, P = 0.005). Further Bland-Altman plots analysis presented good
      agreement between the two systems measurements of location of LES upper margin,
      LES relax ratio and IRP4s. The discomfort indices of subjects' nasal sensation
      were higher when inserting the solid-state catheter [5(3.75-5)] than water
      perfusion one (2.5(2-4)) (Z = -2.471, P = 0.013), as well as the discomfort
      indices of pharyngeal sensation (7.5(4.75-9) vs. 4.5(3.75-6.5)), (Z = -2.354, P =
      0.019). The preparation time for WPC was 40(39-41) minutes, which was much longer
      than that for SSC 32.5(31.75-33) minutes, (Z = -3.087, P = 0.002). And the nurses
      reported it's much easier to insert WPC (Z = -3.126, P = 0.002). CONCLUSIONS: In
      conclusion, most pressure measurements were consistent between WPM and SSM.
      Patients tolerated better with WPC, while for operators, the SSC presented more
      convenient.

PMID- 23134720
TI  - Boolean modeling and fault diagnosis in oxidative stress response.
AB  - BACKGROUND: Oxidative stress is a consequence of normal and abnormal cellular
      metabolism and is linked to the development of human diseases. The effective
      functioning of the pathway responding to oxidative stress protects the cellular
      DNA against oxidative damage; conversely the failure of the oxidative stress
      response mechanism can induce aberrant cellular behavior leading to diseases such
      as neurodegenerative disorders and cancer. Thus, understanding the normal
      signaling present in oxidative stress response pathways and determining possible
      signaling alterations leading to disease could provide us with useful pointers
      for therapeutic purposes. Using knowledge of oxidative stress response pathways
      from the literature, we developed a Boolean network model whose simulated
      behavior is consistent with earlier experimental observations from the
      literature. Concatenating the oxidative stress response pathways with the PI3
      Kinase-Akt pathway, the oxidative stress is linked to the phenotype of apoptosis,
      once again through a Boolean network model. Furthermore, we present an approach
      for pinpointing possible fault locations by using temporal variations in the
      oxidative stress input and observing the resulting deviations in the apoptotic
      signature from the normally predicted pathway. Such an approach could potentially
      form the basis for designing more effective combination therapies against complex
      diseases such as cancer. RESULTS: In this paper, we have developed a Boolean
      network model for the oxidative stress response. This model was developed based
      on pathway information from the current literature pertaining to oxidative
      stress. Where applicable, the behaviour predicted by the model is in agreement
      with experimental observations from the published literature. We have also linked
      the oxidative stress response to the phenomenon of apoptosis via the PI3k/Akt
      pathway. CONCLUSIONS: It is our hope that some of the additional predictions
      here, such as those pertaining to the oscillatory behaviour of certain genes in
      the presence of oxidative stress, will be experimentally validated in the near
      future. Of course, it should be pointed out that the theoretical procedure
      presented here for pinpointing fault locations in a biological network with
      feedback will need to be further simplified before it can be even considered for
      practical biological validation.

PMID- 23134721
TI  - InGaN/GaN multilayer quantum dots yellow-green light-emitting diode with
      optimized GaN barriers.
AB  - InGaN/GaN multilayer quantum dot (QD) structure is a potential type of active
      regions for yellow-green light-emitting diodes (LEDs). The surface morphologies
      and crystalline quality of GaN barriers are critical to the uniformity of InGaN
      QD layers. While GaN barriers were grown in multi-QD layers, we used improved
      growth parameters by increasing the growth temperature and switching the carrier
      gas from N2 to H2 in the metal organic vapor phase epitaxy. As a result, a 10
      layer InGaN/GaN QD LED is demonstrated successfully. The transmission electron
      microscopy image shows the uniform multilayer InGaN QDs clearly. As the injection
      current increases from 5 to 50 mA, the electroluminescence peak wavelength shifts
      from 574 to 537 nm.

PMID- 23134722
TI  - Urethral obstruction from dislodged bladder diverticulum stones: a case report.
AB  - BACKGROUND: Secondary urethral stone although rare, commonly arises from the
      kidneys, bladder or are seen in patients with urethral stricture. These stones
      are either found in the posterior or anterior urethra and do result in acute
      urinary retention. We report urethral obstruction from dislodged bladder
      diverticulum stones. This to our knowledge is the first report from Nigeria and
      in English literature. CASE PRESENTATION: A 69 year old, male, Nigerian with
      clinical and radiological features of acute urinary retention, benign prostate
      enlargement and bladder diverticulum. He had a transurethral resection of the
      prostate (TURP) and was lost to follow up. He re-presented with retained urethral
      catheter of 4 months duration. The catheter was removed but attempt at re-passing
      the catheter failed and a suprapubic cystostomy was performed. Clinical
      examination and plain radiograph of the penis confirmed anterior and posterior
      urethral stones. He had meatotomy and antegrade manual stone extraction with no
      urethra injury. CONCLUSIONS: Urethral obstruction can result from inadequate
      treatment of patient with benign prostate enlargement and bladder diverticulum
      stones. Surgeons in resource limited environment should be conversant with
      transurethral resection of the prostate and cystolithotripsy or open
      prostatectomy and diverticulectomy.

PMID- 23134723
TI  - Legacy of human-induced C erosion and burial on soil-atmosphere C exchange.
AB  - Carbon exchange associated with accelerated erosion following land cover change
      is an important component of the global C cycle. In current assessments, however,
      this component is not accounted for. Here, we integrate the effects of
      accelerated C erosion across point, hillslope, and catchment scale for the 780
      km(2) Dijle River catchment over the period 4000 B.C. to A.D. 2000 to demonstrate
      that accelerated erosion results in a net C sink. We found this long-term C sink
      to be equivalent to 43% of the eroded C and to have offset 39% (17-66%) of the C
      emissions due to anthropogenic land cover change since the advent of agriculture.
      Nevertheless, the erosion-induced C sink strength is limited by a significant
      loss of buried C in terrestrial depositional stores, which lagged the burial. The
      time lag between burial and subsequent loss at this study site implies that the C
      buried in eroded terrestrial deposits during the agricultural expansion of the
      last 150 y cannot be assumed to be inert to further destabilization, and indeed
      might become a significant C source. Our analysis exemplifies that accounting for
      the non-steady-state C dynamics in geomorphic active systems is pertinent to
      understanding both past and future anthropogenic global change.

PMID- 23134724
TI  - Impact of copy number variations (CNVs) on long-range gene regulation at the HoxD
      locus.
AB  - Copy number variations are genomic structural variants that are frequently
      associated with human diseases. Among these copy number variations, duplications
      of DNA segments are often assumed to lead to dosage effects by increasing the
      copy number of either genes or their regulatory elements. We produced a series of
      large targeted duplications within a conserved gene desert upstream of the murine
      HoxD locus. This DNA region, syntenic to human 2q31-32, contains a range of
      regulatory elements required for Hoxd gene transcription, and it is often
      disrupted and/or reorganized in human genetic conditions collectively known as
      the 2q31 syndrome. Unexpectedly, one such duplication led to a transcriptional
      down-regulation in developing digits by impairing physical interactions between
      the target genes and their upstream regulatory elements, thus phenocopying the
      effect obtained when these enhancer sequences are deleted. These results
      illustrate the detrimental consequences of interrupting highly conserved
      regulatory landscapes and reveal a mechanism where genomic duplications lead to
      partial loss of function of nearby located genes.

PMID- 23134725
TI  - Volume conservation principle involved in cell lengthening and nucleus movement
      during tissue morphogenesis.
AB  - Tissue morphogenesis is the process in which coordinated movements and shape
      changes of large numbers of cells form tissues, organs, and the internal body
      structure. Understanding morphogenetic movements requires precise measurements of
      whole-cell shape changes over time. Tissue folding and invagination are thought
      to be facilitated by apical constriction, but the mechanism by which changes near
      the apical cell surface affect changes along the entire apical-basal axis of the
      cell remains elusive. Here, we developed Embryo Development Geometry Explorer, an
      approach for quantifying rapid whole-cell shape changes over time, and we
      combined it with deep-tissue time-lapse imaging based on fast two-photon
      microscopy to study Drosophila ventral furrow formation. We found that both the
      cell lengthening along the apical-basal axis and the movement of the nucleus to
      the basal side proceeded stepwise and were correlated with apical constriction.
      Moreover, cell volume lost apically due to constriction largely balanced the
      volume gained basally by cell lengthening. The volume above the nucleus was
      conserved during its basal movement. Both apical volume loss and cell lengthening
      were absent in mutants showing deficits in the contractile cytoskeleton
      underlying apical constriction. We conclude that a single mechanical mechanism
      involving volume conservation and apical constriction-induced basal movement of
      cytoplasm accounts quantitatively for the cell shape changes and the nucleus
      movement in Drosophila ventral furrow formation. Our study provides a
      comprehensive quantitative analysis of the fast dynamics of whole-cell shape
      changes during tissue folding and points to a simplified model for Drosophila
      gastrulation.

PMID- 23134726
TI  - Gating pore currents and the resting state of Nav1.4 voltage sensor domains.
AB  - Mammalian voltage-gated sodium channels are composed of four homologous voltage
      sensor domains (VSDs; DI, DII, DIII, and DIV) in which their S4 segments contain
      a variable number of positively charged residues. We used single histidine (H)
      substitutions of these charged residues in the Na(v)1.4 channel to probe the
      positions of the S4 segments at hyperpolarized potentials. The substitutions led
      to the formation of gating pores that were detected as proton leak currents
      through the VSDs. The leak currents indicated that the mutated residues are
      accessible from both sides of the membrane. Leak currents of different magnitudes
      appeared in the DI/R1H, DII/R1H, and DIII/R2H mutants, suggesting that the
      resting state position of S4 varies depending on the domain. Here, DI/R1H
      indicates the first arginine R1, in domain DI, has been mutated to histidine. The
      single R1H, R2H, and R3H mutations in DIV did not produce appreciable proton
      currents, indicating that the VSDs had different topologies. A structural model
      of the resting states of the four VSDs of Na(v)1.4 relaxed in their
      membrane/solution environment using molecular dynamics simulations is proposed
      based on the recent Na(v)Ab sodium channel X-ray structure. The model shows that
      the hydrophobic septa that isolate the intracellular and the extracellular media
      within the DI, DII, and DIII VSDs are ~2 A long, similar to those of K(v)
      channels. However, the septum of DIV is longer, which prevents water molecules
      from hydrating the center of the VSD, thus breaking the proton conduction
      pathway. This structural model rationalizes the activation sequence of the
      different VSDs of the Na(v)1.4 channel.

PMID- 23134727
TI  - Chromatin remodeling by the CHD7 protein is impaired by mutations that cause
      human developmental disorders.
AB  - Mutations in the CHD7 gene cause human developmental disorders including CHARGE
      syndrome. Genetic studies in model organisms have further established CHD7 as a
      central regulator of vertebrate development. Functional analysis of the CHD7
      protein has been hampered by its large size. We used a dual-tag system to purify
      intact recombinant CHD7 protein and found that it is an ATP-dependent nucleosome
      remodeling factor. Biochemical analyses indicate that CHD7 has characteristics
      distinct from SWI/SNF- and ISWI-type remodelers. Further investigations show that
      CHD7 patient mutations have consequences that range from subtle to complete
      inactivation of remodeling activity, and that mutations leading to protein
      truncations upstream of amino acid 1899 of CHD7 are likely to cause a hypomorphic
      phenotype for remodeling. We propose that nucleosome remodeling is a key function
      for CHD7 during developmental processes and provide a molecular basis for
      predicting the impact of disease mutations on that function.

PMID- 23134729
TI  - Population-scale sequencing reveals genetic differentiation due to local
      adaptation in Atlantic herring.
AB  - The Atlantic herring (Clupea harengus), one of the most abundant marine fishes in
      the world, has historically been a critical food source in Northern Europe. It is
      one of the few marine species that can reproduce throughout the brackish salinity
      gradient of the Baltic Sea. Previous studies based on few genetic markers have
      revealed a conspicuous lack of genetic differentiation between geographic
      regions, consistent with huge population sizes and minute genetic drift. Here, we
      present a cost-effective genome-wide study in a species that lacks a genome
      sequence. We first assembled a muscle transcriptome and then aligned genomic
      reads to the transcripts, creating an "exome assembly," capturing both exons and
      flanking sequences. We then resequenced pools of fish from a wide geographic
      range, including the Northeast Atlantic, as well as different regions in the
      Baltic Sea, aligned the reads to the exome assembly, and identified 440,817 SNPs.
      The great majority of SNPs showed no appreciable differences in allele frequency
      among populations; however, several thousand SNPs showed striking differences,
      some approaching fixation for different alleles. The contrast between low genetic
      differentiation at most loci and striking differences at others implies that the
      latter category primarily reflects natural selection. A simulation study
      confirmed that the distribution of the fixation index F(ST) deviated
      significantly from expectation for selectively neutral loci. This study provides
      insights concerning the population structure of an important marine fish and
      establishes the Atlantic herring as a model for population genetic studies of
      adaptation and natural selection.

PMID- 23134730
TI  - Mutually helping microbes can evolve by hitchhiking.

PMID- 23134728
TI  - Disruption of PH-kinase domain interactions leads to oncogenic activation of AKT
      in human cancers.
AB  - The protein kinase v-akt murine thymoma viral oncogene homolog (AKT), a key
      regulator of cell survival and proliferation, is frequently hyperactivated in
      human cancers. Intramolecular pleckstrin homology (PH) domain-kinase domain (KD)
      interactions are important in maintaining AKT in an inactive state. AKT
      activation proceeds after a conformational change that dislodges the PH from the
      KD. To understand these autoinhibitory interactions, we generated mutations at
      the PH-KD interface and found that most of them lead to constitutive activation
      of AKT. Such mutations are likely another mechanism by which activation may occur
      in human cancers and other diseases. In support of this likelihood, we found
      somatic mutations in AKT1 at the PH-KD interface that have not been previously
      described in human cancers. Furthermore, we show that the AKT1 somatic mutants
      are constitutively active, leading to oncogenic signaling. Additionally, our
      studies show that the AKT1 mutants are not effectively inhibited by allosteric
      AKT inhibitors, consistent with the requirement for an intact PH-KD interface for
      allosteric inhibition. These results have important implications for therapeutic
      intervention in patients with AKT mutations at the PH-KD interface.

PMID- 23134731
TI  - Host-virus dynamics and subcellular controls of cell fate in a natural
      coccolithophore population.
AB  - Marine viruses are major evolutionary and biogeochemical drivers in marine
      microbial foodwebs. However, an in-depth understanding of the cellular mechanisms
      and the signal transduction pathways mediating host-virus interactions during
      natural bloom dynamics has remained elusive. We used field-based mesocosms to
      examine the "arms race" between natural populations of the coccolithophore
      Emiliania huxleyi and its double-stranded DNA-containing coccolithoviruses
      (EhVs). Specifically, we examined the dynamics of EhV infection and its
      regulation of cell fate over the course of bloom development and demise using a
      diverse suite of molecular tools and in situ fluorescent staining to target
      different levels of subcellular resolution. We demonstrate the concomitant
      induction of reactive oxygen species, caspase-specific activity, metacaspase
      expression, and programmed cell death in response to the accumulation of virus
      derived glycosphingolipids upon infection of natural E. huxleyi populations.
      These subcellular responses to viral infection simultaneously resulted in the
      enhanced production of transparent exopolymer particles, which can facilitate
      aggregation and stimulate carbon flux. Our results not only corroborate the
      critical role for glycosphingolipids and programmed cell death in regulating E.
      huxleyi-EhV interactions, but also elucidate promising molecular biomarkers and
      lipid-based proxies for phytoplankton host-virus interactions in natural systems.

PMID- 23134732
TI  - The transcriptional regulator gene E2 of the Human Papillomavirus (HPV) 16
      influences the radiosensitivity of cervical keratinocytes.
AB  - BACKGROUND: Clinical studies have demonstrated that HPV induced tumors constitute
      a specific subclass of cancer with a better response to radiation treatment. The
      purpose of this study was to investigate meaning of viral E2-gene for
      radiosensitivity. METHODS: W12 cells contain episomal HPV 16 genomes, whereas S12
      cells, which derive from the W12 line, contain HPV DNA as integrated copies.
      Clonogenic survival was analyzed using 96-well in vitro test. Using flow
      cytometry cell cycle analyses were performed. Expression of pRb and p53 were
      analyzed using intracellular staining. RESULTS: W12 cells (intact E2 gene) showed
      a lower survival fraction than S12 cells. W12 cells developed a G2/M block 24 h
      after irradiation with 2 Gy whereas S12 showed no G2/M bloc. After irradiation
      S12 cells developed polyploidy and pRb-positive cells decreased. W12 cells showed
      no change of pRb-positive cells. CONCLUSIONS: Depending on E2 gene status
      differences in cell cycle regulation might cause radioresistance. The E2/E7/pRb
      pathway seems to influence HPV-induced radiosensitivity. Our experiments
      demonstrated an effect of HPV on radiosensitivity of cervical keratinocytes via
      viral transcription regulator E2 pathway.

PMID- 23134733
TI  - Assessing the efficacy of molecularly targeted agents on cell line-based
      platforms by using system identification.
AB  - BACKGROUND: Molecularly targeted agents (MTAs) are increasingly used for cancer
      treatment, the goal being to improve the efficacy and selectivity of cancer
      treatment by developing agents that block the growth of cancer cells by
      interfering with specific targeted molecules needed for carcinogenesis and tumor
      growth. This approach differs from traditional cytotoxic anticancer drugs. The
      lack of specificity of cytotoxic drugs allows a relatively straightforward
      approach in preclinical and clinical studies, where the optimal dose has usually
      been defined as the "maximum tolerated dose" (MTD). This toxicity-based dosing
      approach is founded on the assumption that the therapeutic anticancer effect and
      toxic effects of the drug increase in parallel as the dose is escalated. On the
      contrary, most MTAs are expected to be more selective and less toxic than
      cytotoxic drugs. Consequently, the maximum therapeutic effect may be achieved at
      a "biologically effective dose" (BED) well below the MTD. Hence, dosing study for
      MTAs should be different from cytotoxic drugs. Enhanced efforts to molecularly
      characterize the drug efficacy for MTAs in preclinical models will be valuable
      for successfully designing dosing regimens for clinical trials. RESULTS: A novel
      preclinical model combining experimental methods and theoretical analysis is
      proposed to investigate the mechanism of action and identify pharmacodynamic
      characteristics of the drug. Instead of fixed time point analysis of the drug
      exposure to drug effect, the time course of drug effect for different doses is
      quantitatively studied on cell line-based platforms using system identification,
      where tumor cells' responses to drugs through the use of fluorescent reporters
      are sampled over a time course. Results show that drug effect is time-varying and
      higher dosages induce faster and stronger responses as expected. However, the
      drug efficacy change along different dosages is not linear; on the contrary,
      there exist certain thresholds. This kind of preclinical study can provide
      valuable suggestions about dosing regimens for the in vivo experimental stage to
      increase productivity.

PMID- 23134734
TI  - A spectrophotometric assay for quantitative measurement of aminoacyl-tRNA
      synthetase activity.
AB  - Aminoacyl-tRNA synthetases are enzymes that charge specific tRNAs with their
      cognate amino acids and play an essential role in the initial steps of protein
      synthesis. Because these enzymes are attractive targets for drug development in
      many microorganisms, there is a pressing need for assays suitable for compound
      screening. We developed (1) a high-throughput assay for measuring aminoacyl-tRNA
      synthetase activity and (2) an accompanying method for preparing the tRNA
      substrate. The assay can be performed in 96-well plates and relies on malachite
      green detection of pyrophosphate (Pi) as an indicator of aminoacyl-tRNA
      synthetase activity. Analysis of Trypanosoma brucei isoleucyl-tRNA synthetase
      (IleRS) activity showed that the assay exhibits sensitivity to picomoles of
      product and yielded a Z' factor of 0.56. We show that this assay is applicable to
      other aminoacyl-tRNA synthetases and to enzyme inhibition studies. Using this
      assay, we found that the compound NSC616354 inhibits recombinant IleRS with an
      IC50 of 0.6 uM. Enzymology studies were also performed with rIleRS and its Km and
      kcat determined as 3.97 * 10(-5) mol/L and 312 S(-1), respectively. This assay
      will facilitate the screening of compounds to identify inhibitors of aminoacyl
      tRNA synthetases.

PMID- 23134735
TI  - Development and validation of a high-throughput intrinsic ATPase activity assay
      for the discovery of MEKK2 inhibitors.
AB  - The kinase MEKK2 (MAP3K2) has recently been implicated in tumor growth and
      metastasis. Thus, selective inhibition of MEKK2 may be a novel strategy for
      cancer therapy. To identify inhibitors of MEKK2 kinase activity, we have
      developed a novel activity assay for MEKK2 based on the discovery that
      recombinant purified MEKK2 has intrinsic ATPase activity. This MEKK2 ATPase assay
      was validated for enzyme identity and enzymatic purity by multiple methods
      including mass spectrometry analysis, testing different sources of MEKK2 and
      comparing ATPase assay IC50 data for multiple inhibitors to literature values and
      to IC50 data generated using MEKK2 binding and transphosphorylation assays. Taken
      together, these data indicated that genuine MEKK2 activity was being measured in
      this assay and no other ATPases contributed to the signal. A miniaturized version
      of the assay was validated for high-throughput screening, and compound libraries
      were screened. The screening hits generated comparable potencies in the MEKK2
      intrinsic ATPase, binding, and transphosphorylation assays. We identified a novel
      MEKK2 inhibitor and confirmed that crizotinib and bosutinib are potent in vitro
      inhibitors of MEKK2 activity with IC50 values of <100 nM. Thus, this assay has
      utility for the discovery of small-molecule inhibitors of MEKK2 activity.

PMID- 23134736
TI  - Human stem cells ameliorate auditory evoked responses in a model of neuropathy.
AB  - Stem cells have been touted as a potential source of replacement cells for the
      treatment of severe-to-profoundly deaf individuals, including possible combined
      therapy with a cochlear implant. The success of such a therapy is dependent on a
      number of factors, but of critical importance is the functional incorporation of
      transplanted cells into the peripheral and central auditory systems. In a major
      breakthrough, Chen and colleagues recently reported the restoration of hearing
      thresholds by up to 46% following the transplantation of human pluripotent stem
      cells in a rodent auditory neuropathy model. Improved function was matched with
      new synapse formation in the peripheral and central aspects of the auditory
      system. The findings have promising clinical implications for patients with
      auditory neuropathy. Still to be elucidated are the long-term survival and
      function of transplanted cells, the precise mechanism by which hearing is
      restored, and whether further improvement is possible when combined with
      electrical stimulation from a cochlear implant. 

PMID- 23134737
TI  - Residual effects of muscle strength and muscle power training and detraining on
      physical function in community-dwelling prefrail older adults: a randomized
      controlled trial.
AB  - BACKGROUND: Although resistance exercise interventions have been shown to be
      beneficial in prefrail or frail older adults it remains unclear whether there are
      residual effects when the training is followed by a period of detraining. The aim
      of this study was to establish the sustainability of a muscle power or muscle
      strength training effect in prefrail older adults following training and
      detraining. METHODS: 69 prefrail community-dwelling older adults, aged 65-94
      years were randomly assigned into three groups: muscle strength training (ST),
      muscle power training (PT) or controls. The exercise interventions were performed
      for 60 minutes, twice a week over 12 weeks. Physical function (Short Physical
      Performance Battery=SPPB), muscle power (sit-to-stand transfer=STS), self
      reported function (SF-LLFDI) and appendicular lean mass (aLM) were measured at
      baseline and at 12, 24 and 36 weeks after the start of the intervention. RESULTS:
      For the SPPB, significant intervention effects were found at 12 weeks in both
      exercise groups (ST: p = 0.0047; PT: p = 0.0043). There were no statistically
      significant effects at 24 and 36 weeks. In the ST group, the SPPB declined
      continuously after stop of exercising whereas the PT group and controls remained
      unchanged. No effects were found for muscle power, SF-LLFDI and aLM. CONCLUSIONS:
      The results showed that both intervention types are equally effective at 12 weeks
      but did not result in statistically significant residual effects when the
      training is followed by a period of detraining. The unchanged SPPB score at 24
      and 36 weeks in the PT group indicates that muscle power training might be more
      beneficial than muscle strength training. However, more research is needed on the
      residual effects of both interventions. Taken the drop-out rates (PT: 33%, ST:
      21%) into account, muscle power training should also be used more carefully in
      prefrail older adults. TRIAL REGISTRATION: This trial has been registered with
      clinicaltrials.gov (NCT00783159)

PMID- 23134738
TI  - Application of Max-SAT-based ATPG to optimal cancer therapy design.
AB  - BACKGROUND: Cancer and other gene related diseases are usually caused by a
      failure in the signaling pathway between genes and cells. These failures can
      occur in different areas of the gene regulatory network, but can be abstracted as
      faults in the regulatory function. For effective cancer treatment, it is
      imperative to identify faults and select appropriate drugs to treat the faults.
      In this paper, we present an extensible Max-SAT based automatic test pattern
      generation (ATPG) algorithm for cancer therapy. This ATPG algorithm is based on
      Boolean Satisfiability (SAT) and utilizes the stuck-at fault model for
      representing signaling faults. A weighted partial Max-SAT formulation is used to
      enable efficient selection of the most effective drug. RESULTS: Several usage
      cases are presented for fault identification and drug selection. These cases
      include the identification of testable faults, optimal drug selection for
      single/multiple known faults, and optimal drug selection for overall fault
      coverage. Experimental results on growth factor (GF) signaling pathways
      demonstrate that our algorithm is flexible, and can yield an exact solution for
      each feature in much less than 1 second.

PMID- 23134739
TI  - Pollen exposure in pregnancy and infancy and risk of asthma hospitalisation - a
      register based cohort study.
AB  - BACKGROUND: A seasonal effect of month of birth and risk of allergic disease has
      been suggested by numerous studies. Few studies have directly measured pollen
      exposures at different points during pregnancy and in early life, and assessed
      their effects on risk of respiratory disease outcomes. METHODS: Pollen exposure
      was calculated for the first and last 12 weeks of pregnancy and the first 12
      weeks of infancy for all children conceived by women residing in Stockholm,
      Sweden, between 1988 and 1995. Hospital admission data for respiratory conditions
      in the first year of life was also collected. RESULTS: Out of 110,381 children,
      940 had been hospitalised for asthma by 12-months of age. Pollen levels showed
      both marked seasonal variations and between year differences. Exposure to high
      levels of pollen in the last 12 weeks of pregnancy was associated with an
      increased risk of asthma hospitalisation (aOR = 1.35, 95% CI = 1.07-1.71 for
      highest quartile versus remaining infants). Exposure to high levels of pollen in
      the first three months of life was associated with a reduced risk (aOR = 0.76,
      95% CI = 0.59-0.98) but only in children of heavy smoking mothers. CONCLUSIONS:
      High levels of pollen exposure during late pregnancy were somewhat unexpectedly
      associated with an elevated risk of hospitalisation for asthma within the first
      year of life.

PMID- 23134740
TI  - Inhibition and biotransformation potential of naphthenic acids under different
      electron accepting conditions.
AB  - Naphthenic acids (NAs) are a complex group of alkyl-substituted acyclic,
      monocyclic and polycyclic carboxylic acids present in crude oil, oil sands
      process water and tailings ponds, as well as in refinery wastewater. Bioassays
      were performed to investigate the biotransformation potential and inhibitory
      effect of a commercial NA mixture to nitrification, denitrification and
      fermentation/methanogenesis using mixed cultures not previously exposed to NAs.
      NAs inhibited nitrification in a mixed aerobic heterotrophic/nitrifying culture
      at concentrations as low as 80 mg NA/L, whereas, an enriched nitrifying culture
      was only affected at 400 mg NA/L. The lower nitrification inhibition in the
      latter assay is attributed to the higher population size of nitrosofying and
      nitrifying bacteria compared to the mixed heterotrophic/nitrifying culture. The
      NA mixture was not inhibitory to denitrifiers up to 400 mg/L. At higher NA
      concentrations, cell lysis was pronounced and lysis products were the main source
      of degradable carbon driving denitrification in culture series prepared without
      an external carbon source. In the presence of a degradable external carbon
      source, no difference was observed in nitrate reduction rates or nitrogen gas
      production at all NA concentrations tested. Methanogenesis was completely
      inhibited at NA concentrations equal to or higher than 200 mg/L. Methanogenic
      culture series amended with 80 mg NA/L were transiently inhibited and methane
      production in culture series prepared with NAs and an external carbon source or
      NAs only recovered in 136 and 41 days, respectively. Accumulation of volatile
      fatty acids was observed at inhibitory NA concentrations; however, carbon dioxide
      production was not affected by NAs, indicating that fermentation and acidogenesis
      were not affected by NAs. NAs were not degraded under nitrate-reducing or
      fermentative/methanogenic conditions used in the present study, regardless of the
      presence or not of another, degradable carbon/energy source.

PMID- 23134741
TI  - Evaluation of microbial regrowth potential by assimilable organic carbon in
      various reclaimed water and distribution systems.
AB  - Microbial regrowth introduces several problems to the use of reclaimed water,
      such as health concerns, aesthetic deterioration, and biofouling. This study
      evaluated assimilable organic carbon (AOC), which is a part of the biodegradable
      organic matter promoting microbial growth, in water reclamation systems in Japan.
      The AOC concentration in the reclaimed water from various treatment processes
      ranged between 36 and 446 MUg C/L (median 316 MUg C/L). The AOC concentration in
      the reclaimed water from the plants equipped with ozonation was significantly
      higher - more than two times - than that in the reclaimed water from plants
      equipped with other processes. UV and chlorine also changed the AOC concentration
      slightly. Moreover, reverse osmosis produced reclaimed water with the lowest AOC
      content. Processes equipped with membrane filtration were effective in removing
      seed microorganisms that enter the distribution system. Microbial growth in
      reclaimed water distribution systems occurred when the total and free residual
      chlorine was lower than 0.36 and 0.09 mg/L, respectively. The AOC reduction
      occurred simultaneously with regrowth, which suggests that AOC could support
      microbial growth in reclaimed-water-distribution systems. As the residual
      chlorine is often depleted during distribution and storage, it is essential to
      control the AOC to suppress microbial growth.

PMID- 23134742
TI  - Adaptive reference update (ARU) algorithm. A stochastic search algorithm for
      efficient optimization of multi-drug cocktails.
AB  - BACKGROUND: Multi-target therapeutics has been shown to be effective for treating
      complex diseases, and currently, it is a common practice to combine multiple
      drugs to treat such diseases to optimize the therapeutic outcomes. However,
      considering the huge number of possible ways to mix multiple drugs at different
      concentrations, it is practically difficult to identify the optimal drug
      combination through exhaustive testing. RESULTS: In this paper, we propose a
      novel stochastic search algorithm, called the adaptive reference update (ARU)
      algorithm, that can provide an efficient and systematic way for optimizing multi
      drug cocktails. The ARU algorithm iteratively updates the drug combination to
      improve its response, where the update is made by comparing the response of the
      current combination with that of a reference combination, based on which the
      beneficial update direction is predicted. The reference combination is
      continuously updated based on the drug response values observed in the past,
      thereby adapting to the underlying drug response function. To demonstrate the
      effectiveness of the proposed algorithm, we evaluated its performance based on
      various multi-dimensional drug functions and compared it with existing
      algorithms. CONCLUSIONS: Simulation results show that the ARU algorithm
      significantly outperforms existing stochastic search algorithms, including the
      Gur Game algorithm. In fact, the ARU algorithm can more effectively identify
      potent drug combinations and it typically spends fewer iterations for finding
      effective combinations. Furthermore, the ARU algorithm is robust to random
      fluctuations and noise in the measured drug response, which makes the algorithm
      well-suited for practical drug optimization applications.

PMID- 23134743
TI  - Enhanced recombinant protein production and differential expression of molecular
      chaperones in sf-caspase-1-repressed stable cells after baculovirus infection.
AB  - BACKGROUND: There are few studies that have examined the potential of RNA
      inference (RNAi) to increase protein production in the baculovirus expression
      vector system (BEVS). Spodoptera frugiperda (fall armyworm) (Sf)-caspase-1
      repressed stable cells exhibit resistance to apoptosis and enhancement of
      recombinant protein production. However, the mechanism of recombinant protein
      augmentation in baculovirus-infected Caspase-repressed insect cells has not been
      elucidated. RESULTS: In the current study, we utilized RNAi-mediated Sf-caspase-1
      repressed stable cells to clarify how the resistance to apoptosis can enhance
      both intracellular (firefly luciferase) and extracellular (secreted alkaline
      phosphatase [SEAP]) recombinant protein production in BEVS. Since the expression
      of molecular chaperones is strongly associated with the maximal production of
      exogenous proteins in BEVS, the differential expression of molecular chaperones
      in baculovirus-infected stable cells was also analyzed in this study. CONCLUSION:
      The data indicated that the retention of expression of molecular chaperones in
      baculovirus-infected Sf-caspase-1-repressed stable cells give the higher
      recombinant protein accumulation.

PMID- 23134744
TI  - Room-temperature super-extraction system (RTSES) optimizes the anxiolytic- and
      antidepressant-like behavioural effects of traditional Xiao-Yao-San in mice.
AB  - BACKGROUND: Xiao-Yao-San (XYS) is a Chinese medicinal formula for treating
      anxiety and depression. This study aims to evaluate the use of a room-temperature
      super-extraction system (RTSES) to extract the major active components of XYS and
      enhance their psycho-pharmacological effects. METHODS: The neuroprotective roles
      of XYS/RTSES against reserpine-derived neurotoxicity were evaluated using a glial
      cell injury system (in vitro) and a depression-like C57BL/6 J mouse model (in
      vivo). The anxiolytic-behavioural effects were measured by the elevated plus-maze
      (EPM) test and the antidepressant effects were evaluated by the forced swimming
      test (FST) and tail suspension test (TST). Glucose tolerance and insulin
      resistance were assayed by ELISA. The expression of 5-HT1A receptors in the
      prefrontal cortex was examined by western blotting. RESULTS: XYS/RTSES (300
      MUg/mL) diminished reserpine-induced glial cell death more effectively than
      either XYS (300 MUg/mL) or fluoxetine (30 MUM) at 24 h (P = 0.0481 and P = 0.054,
      respectively). Oral administration of XYS/RTSES (500 mg/kg/day) for 4 consecutive
      weeks significantly elevated the ratios of entries (open arms/closed arms; P =
      0.0177) and shuttle activity (P = 0.00149) on the EPM test, and reduced the
      immobility time by 90% on the TST (P = 0.00000538) and FST (P = 0.0000053839).
      XYS/RTSES also improved the regulation of blood glucose (P = 0.0305) and
      increased the insulin sensitivity (P = 0.0093). The Western blot results
      indicated that the activation of cerebral 5-HT1A receptors may be involved in the
      mechanisms of XYS/RTSES actions. CONCLUSION: The RTSES could provide a novel
      method for extracting effective anxiolytic- and antidepressant-like substances.
      XYS/RTSES improved the regulation of blood glucose and increased the insulin
      sensitivity in reserpine-induced anxiety and depression. Neuroprotection of glial
      cells and activation of cerebral 5-HT1A receptors were also involved.

PMID- 23134746
TI  - [Better multidisciplinary team meetings are linked to better care].
AB  - Discussing a patient in an oncology multidisciplinary team meeting (MTM)
      increases the value of the quality of the treatment chosen. MTMs are increasingly
      mentioned in guidelines and indicator sets. Based on literature review and
      observations, the Comprehensive Cancer Centre Netherlands (CCCNL), in
      collaboration with IQ Healthcare and the Department of Medical Oncology of the
      UMC St Radboud Nijmegen in the Netherlands, has conducted research into the
      quality criteria for a good MTM. Two of our studies show that the organisation of
      MTMs can be significantly improved. Based on the results, we developed a
      checklist to accomplish this. The most significant areas of improvement for
      optimising the organisation of MTMs are: (a) the presence of specialists from all
      relevant disciplines; (b) a capable chairman who promotes the efficiency of the
      MTM; and (c) the reduction of intruding factors, such as mobile phones and
      participants who walk in and out.

PMID- 23134745
TI  - [DRESS syndrome as a result of sulfasalazine use].
AB  - A 24-year-old female developed DRESS syndrome (Drug Reaction with Eosinophilia
      and Systemic Symptoms) as a result of sulfasalazine use. The DRESS syndrome is a
      severe and acute hypersensitivity reaction that can be caused by a variety of
      drugs. The clinical presentation is diverse; the most common symptoms are fever,
      exanthema and lymphadenopathy. Haematologic abnormalities such as leukocytosis,
      accompanied primarily with eosinophilia, and sometimes atypical lymphocytes are
      also frequently reported. In most cases the DRESS syndrome needs no further
      treatment after discontinuation of the associated drug. However, 20% of patients
      are severely affected and the DRESS syndrome is potentially life-threatening. The
      patient was successfully treated with a glucocorticoid and an antihistamine.

PMID- 23134747
TI  - [Working with the Dutch Standard of Care for COPD: using the 'Nijmegen Clinical
      Screening Instrument' as an aid].
AB  - In the Dutch Standard of Care for chronic obstructive pulmonary disease (COPD)
      the patient, not the illness, is now central. Additionally, treatment is no
      longer exclusively guided by the degree of airway obstruction but by the burden
      of disease (also called 'integral health status'). Consequently, COPD care will
      be more intensive and more complex. The Nijmegen Clinical Screening Instrument
      (NCSI) method offers a guide for the patient and the caregiver to help execute
      the standard of care effectively and efficiently. Using this method, the burden
      of disease is assessed in detail. An integral intervention helps in formulating
      treatment goals (patient-tailored treatment), and in motivating patients to
      adhere to these treatment goals. A special condensed version of the NCSI is
      suitable for monitoring the patient. The method is web-based, which facilitates
      the assessment and monitoring of the patient.

PMID- 23134748
TI  - [Exercise-induced oedema due to hormone-containing intrauterine device].
AB  - BACKGROUND: Oedema is a known adverse effect of the levonorgestrel-containing
      intrauterine device (Mirena IUD). However, exercise-induced oedema has not been
      described before. CASE DESCRIPTION: A 38-year-old woman presented with symptoms
      of diffuse, exercise-induced oedema and dyspnoea. Tests for heart failure and
      other causes of oedema showed no abnormalities. All symptoms resolved
      spontaneously after the patient initiated removal of the IUD. CONCLUSION: The
      pathophysiology of exercise-induced oedema is still poorly understood. When
      confronted with a patient with oedema (induced by exercise or other cause), the
      most common causes must first be excluded. If no explanation can be found, then
      the effects of medication must not be overlooked.

PMID- 23134751
TI  - [Hip fracture in patients with dementia: surgery is not always the best
      alternative].
AB  - Patients with dementia are at risk of hip fracture. The prognosis of
      rehabilitation after surgery is less favourable than in the general population,
      because of higher mortality, more complications and a longer rehabilitation
      period. We present 2 female patients with dementia (77 and 86 years old) who each
      received a different therapy: one surgical, the other conservative. Dutch elderly
      care physicians make use of advance care planning to determine how to make
      medical decisions. The policy for treatment might be curative, palliative or
      symptomatic. When making a medical decision, it is important to consider if a
      treatment is effective, proportional and if the intended outcome is desirable. In
      some cases of hip fracture in patients with dementia, conservative treatment and
      withholding surgery can be good care. More investigation is needed for further
      evidence-based decision-making.

PMID- 23134752
TI  - [Heart failure with preserved ejection fraction: Diastolic heart failure].
AB  - Heart failure with preserved ejection fraction (HF-PEF) is part of the 'heart
      failure spectrum', but differs pathophysiologically from heart failure with
      reduced ejection fraction (HF-REF). Metabolic abnormalities in HF-PEF cause
      intrinsic stiffness of the cardiac myocyte and alternation of the collagen turn
      over in the extracellular matrix of the heart. HF-PEF is most often present in
      elderly women with a history of hypertension, diabetes mellitus or metabolic
      syndrome, and obesity. Signs of fluid retention are often not present on physical
      examination in patients with HF-PEF. The most notable echocardiographic
      abnormalities seen in HF-PEF are an enlarged left atrium with hypertrophy,
      reduced left ventricular relaxation and elevated filling pressures. Co-morbidly
      and advanced age are largely determinant for mortality, which in HF-PEF is
      somewhat lower than in HF-REF. Evidence-based drug therapy for HF-PEF is
      currently lacking; ongoing studies are evaluating medications other than the well
      established drugs used to treat HF-REF.

PMID- 23134753
TI  - [Tender love and care do not heal all wounds].
AB  - The concept of integrated care, which implies a team of medical specialists,
      general physicians, specialized nurses and psychologists, is increasingly
      advocated, but often without appropriate high level evidence. Two independent and
      high quality multicenter randomized clinical trials evaluated the benefits of the
      integrated care model compared to usual care for venous leg ulcers and chronic
      hand dermatitis in the Netherlands. Adherence to compression stockings in
      patients with venous leg ulcers remained low in the integrated care and control
      groups. After 18 months, the likelihood of developing a recurrent ulcer was
      comparable in both groups. Additional care and counselling decreased the Hand
      Eczema Severity Index in patients with severe hand dermatitis, but the difference
      does not seem to be clinically relevant. Although the concept of integrated care
      programs sounds promising, the benefits for hand dermatitis and venous leg ulcers
      are disappointing and are not likely to be cost-effective.

PMID- 23134755
TI  - Canadian society of allergy and clinical immunology annual scientific meeting
      2012 calgary, Canada.  11-14 october 2012. Abstracts.

PMID- 23134754
TI  - The contribution of FTO and UCP-1 SNPs to extreme obesity, diabetes and
      cardiovascular risk in Brazilian individuals.
AB  - BACKGROUND: Obesity has become a common human disorder associated with
      significant morbidity and mortality and adverse effects on quality of life.
      Sequence variants in two candidate genes, FTO and UCP-1, have been reported to be
      overrepresented in obese Caucasian population. The association of these genes
      polymorphisms with the obesity phenotype in a multiethnic group such as the
      Brazilian population has not been previously reported. METHODS: To assess the
      putative contribution of both FTO and UCP-1 to body mass index (BMI) and
      cardiovascular risk we genotyped SNPs rs9939609 (FTO) and rs6536991, rs22705565
      and rs12502572 (UCP-1) from 126 morbidly obese subjects (BMI 42.9 +/- 5.6 kg/m2,
      mean +/- SE) and 113 normal-weight ethnically matched controls (BMI 22.6 +/- 3.5
      kg/m2, mean +/- SE). Waist circumference, blood pressure, glucose and serum
      lipids were also measured. Each sample was also genotyped for 40 biallelic short
      insertion/deletion polymorphism (indels) for ethnic assignment and to estimate
      the proportion of European, African and Amerindian biogeographical ancestry in
      the Brazilian population. RESULTS: Cases did not differ from controls in the
      proportions of genomic ancestry. The FTO SNP rs9939609 and UCP-1 SNP rs6536991
      were significantly associated with BMI (p= 0.04 and p<0.0001 respectively). An
      allele dose dependent tendency was observed for BMI for rs6536991 sample of
      controls. No other significant associations between any SNP and hypertension,
      hyperlipidemia and diabetes were noted after correction for BMI and no
      significant synergistic effect between FTO and UCP-1 SNPs with obesity were
      noted. There was not an association between rs9939609 (FTO) and rs6536991 (UCP-1)
      in with maximum weight loss after 1 year in 94 obese patients who underwent
      bariatric surgery. CONCLUSION: Our data are consistent with FTO rs9939609 and UCP
      1 rs6536991 common variants as contributors to obesity in the Brazilian
      population.

PMID- 23134756
TI  - Reducing confounding and suppression effects in TCGA data: an integrated analysis
      of chemotherapy response in ovarian cancer.
AB  - BACKGROUND: Despite initial response in adjuvant chemotherapy, ovarian cancer
      patients treated with the combination of paclitaxel and carboplatin frequently
      suffer from recurrence after few cycles of treatment, and the underlying
      mechanisms causing the chemoresistance remain unclear. Recently, The Cancer
      Genome Atlas (TCGA) research network concluded an ovarian cancer study and
      released the dataset to the public. The TCGA dataset possesses large sample size,
      comprehensive molecular profiles, and clinical outcome information; however,
      because of the unknown molecular subtypes in ovarian cancer and the great
      diversity of adjuvant treatments TCGA patients went through, studying
      chemotherapeutic response using the TCGA data is difficult. Additionally, factors
      such as sample batches, patient ages, and tumor stages further confound or
      suppress the identification of relevant genes, and thus the biological functions
      and disease mechanisms. RESULTS: To address these issues, herein we propose an
      analysis procedure designed to reduce suppression effect by focusing on a
      specific chemotherapeutic treatment, and to remove confounding effects such as
      batch effect, patient's age, and tumor stages. The proposed procedure starts with
      a batch effect adjustment, followed by a rigorous sample selection process. Then,
      the gene expression, copy number, and methylation profiles from the TCGA ovarian
      cancer dataset are analyzed using a semi-supervised clustering method combined
      with a novel scoring function. As a result, two molecular classifications, one
      with poor copy number profiles and one with poor methylation profiles, enriched
      with unfavorable scores are identified. Compared with the samples enriched with
      favorable scores, these two classifications exhibit poor progression-free
      survival (PFS) and might be associated with poor chemotherapy response
      specifically to the combination of paclitaxel and carboplatin. Significant genes
      and biological processes are detected subsequently using classical statistical
      approaches and enrichment analysis. CONCLUSIONS: The proposed procedure for the
      reduction of confounding and suppression effects and the semi-supervised
      clustering method are essential steps to identify genes associated with the
      chemotherapeutic response.

PMID- 23134757
TI  - Fluxes of nitrous oxide and methane in different coastal Suaeda salsa marshes of
      the Yellow River estuary, China.
AB  - The spatial and temporal variations of the fluxes of nitrous oxide (N(2)O) and
      methane (CH(4)) and associated abiotic sediment parameters were quantified for
      the first time across the coastal marsh dominated by Suaeda salsa in the Yellow
      River estuary during 2009/2010. During all times of day and the seasons measured,
      N(2)O and CH(4) fluxes from coastal marsh ranged from -0.0147 mg N(2)O m(-2) h(
      1) to 0.0982 mg N(2)O m(-2) h(-1) and -0.7421 mg CH(4) m(-2) h(-1) to 0.4242 mg
      CH(4) m(-2) h(-1), respectively. The mean N(2)O fluxes in spring, summer, autumn
      and winter were 0.0325 mg N(2)O m(-2) h(-1), 0.0089 mg N(2)O m(-2) h(-1), 0.0119
      mg N(2)O m(-2) h(-1) and 0.0140 mg N(2)O m(-2) h(-1), and the average CH(4)
      fluxes were -0.0109 mg CH(4) m(-2) h(-1), -0.0174 mg CH(4) m(-2) h(-1), -0.0141
      mg CH(4) m(-2) h(-1) and -0.0089 mg CH(4) m(-2) h(-1), respectively, indicating
      that the coastal marsh acted as N(2)O source and CH(4) sink. Both N(2)O and CH(4)
      fluxes differed significantly between times of day of sampling. N(2)O fluxes
      differed significantly between sampling seasons as well as between sampling
      positions, while CH(4) fluxes had no significant differences between seasons or
      positions. Temporal variations of N(2)O emissions were probably related to the
      effects of vegetation (S. salsa) during summer and autumn and the frequent
      freeze/thaw cycle of sediment during spring and winter, while those of CH(4)
      fluxes were controlled by the interactions of thermal conditions and other
      abiotic factors (soil moisture and salinity). Spatial variations of N(2)O and
      CH(4) fluxes were primarily affected by soil moisture fluctuation derived from
      astronomic tide, sediment substrate and vegetation composition. N(2)O and CH(4)
      fluxes, expressed as CO(2)-equivaltent (CO(2)-e) emissions, showed that N(2)O
      comprised the principal part of total calculated CO(2)-e emissions during spring
      and winter, while the contributions of CH(4) could not be ignored during summer
      and autumn. This study highlights the importance of seasonal N(2)O and CH(4)
      contributions, particularly during times of significant CH(4) consumption. For
      the accurate up-scaling of N(2)O and CH(4) fluxes to annual rates, a careful
      sampling design at site-level is required to capture the potentially considerable
      temporal and spatial variations of N(2)O and CH(4) emissions.

PMID- 23134758
TI  - A modulator based regulatory network for ERalpha signaling pathway.
AB  - BACKGROUND: Estrogens control multiple functions of hormone-responsive breast
      cancer cells. They regulate diverse physiological processes in various tissues
      through genomic and non-genomic mechanisms that result in activation or
      repression of gene expression. Transcription regulation upon estrogen stimulation
      is a critical biological process underlying the onset and progress of the
      majority of breast cancer. ERalpha requires distinct co-regulator or modulators
      for efficient transcriptional regulation, and they form a regulatory network.
      Knowing this regulatory network will enable systematic study of the effect of
      ERalpha on breast cancer. METHODS: To investigate the regulatory network of
      ERalpha and discover novel modulators of ERalpha functions, we proposed an
      analytical method based on a linear regression model to identify translational
      modulators and their network relationships. In the network analysis, a group of
      specific modulator and target genes were selected according to the functionality
      of modulator and the ERalpha binding. Network formed from targets genes with
      ERalpha binding was called ERalpha genomic regulatory network; while network
      formed from targets genes without ERalpha binding was called ERalpha non-genomic
      regulatory network. Considering the active or repressive function of ERalpha,
      active or repressive function of a modulator, and agonist or antagonist effect of
      a modulator on ERalpha, the ERalpha/modulator/target relationships were
      categorized into 27 classes. RESULTS: Using the gene expression data and ERalpha
      Chip-seq data from the MCF-7 cell line, the ERalpha genomic/non-genomic
      regulatory networks were built by merging ERalpha/ modulator/target triplets (TF,
      M, T), where TF refers to the ERalpha, M refers to the modulator, and T refers to
      the target. Comparing these two networks, ERalpha non-genomic network has lower
      FDR than the genomic network. In order to validate these two networks, the same
      network analysis was performed in the gene expression data from the ZR-75.1 cell.
      The network overlap analysis between two cancer cells showed 1% overlap for the
      ERalpha genomic regulatory network, but 4% overlap for the non-genomic regulatory
      network. CONCLUSIONS: We proposed a novel approach to infer the
      ERalpha/modulator/target relationships, and construct the genomic/non-genomic
      regulatory networks in two cancer cells. We found that the non-genomic regulatory
      network is more reliable than the genomic regulatory network.

PMID- 23134759
TI  - Exercise regulation of intestinal tight junction proteins.
AB  - Gastrointestinal distress, such as diarrhoea, cramping, vomiting, nausea and
      gastric pain are common among athletes during training and competition. The
      mechanisms that cause these symptoms are not fully understood. The stress of heat
      and oxidative damage during exercise causes disruption to intestinal epithelial
      cell tight junction proteins resulting in increased permeability to luminal
      endotoxins. The endotoxin moves into the blood stream leading to a systemic
      immune response. Tight junction integrity is altered by the phosphoylation state
      of the proteins occludin and claudins, and may be regulated by the type of
      exercise performed. Prolonged exercise and high-intensity exercise lead to an
      increase in key phosphorylation enzymes that ultimately cause tight junction
      dysfunction, but the mechanisms are different. The purpose of this review is to
      (1) explain the function and physiology of tight junction regulation, (2) discuss
      the effects of prolonged and high-intensity exercise on tight junction
      permeability leading to gastrointestinal distress and (3) review agents that may
      increase or decrease tight junction integrity during exercise.

PMID- 23134760
TI  - The cost of physical inactivity: moving into the 21st century.

PMID- 23134761
TI  - Growth in the Physiotherapy Evidence Database (PEDro) and use of the PEDro scale.

PMID- 23134762
TI  - Correction of vitamin D deficiency in critically ill patients - VITdAL@ICU study
      protocol of a double-blind, placebo-controlled randomized clinical trial.
AB  - BACKGROUND: Vitamin D deficiency is associated with multiple adverse health
      outcomes including increased morbidity and mortality in the general population
      and in critically ill patients. However, no randomized controlled trial has
      evaluated so far whether treatment with sufficiently large doses of vitamin D can
      improve clinical outcome of patients in an intensive care setting.
      METHODS/DESIGN: The VITdAL@ICU trial is an investigator-initiated, non
      commercial, double-blind, placebo-controlled randomized clinical trial. This
      study compares high-dose oral cholecalciferol (vitamin D3) versus placebo
      treatment in a mixed population of 480 critically ill patients with low 25
      hydroxyvitamin-D levels at study enrollment (<= 20ng/ml). Following an initial
      loading dose of 540,000 IU of vitamin D3, patients receive 90,000 IU of vitamin
      D3 on a monthly basis for 5 months. The study is designed to compare clinical
      outcome in the two study arms with the primary endpoint being length of hospital
      stay. Secondary endpoints include among others length of ICU stay, the percentage
      of patients with 25(OH)D levels > 30 ng/ml at day 7, ICU and hospital mortality
      and duration of mechanical ventilation. We describe here the VITdAL@ICU study
      protocol for the primary report. DISCUSSION: This trial is designed to evaluate
      whether high-dose vitamin D3 is able to improve morbidity and mortality in a
      mixed population of adult critically ill patients and correct vitamin D
      deficiency safely. TRIAL REGISTRATION: ClinicalTrials: NCT01130181.

PMID- 23134763
TI  - The origins of evidence-based medicine--a personal perspective.

PMID- 23134764
TI  - Interaction of the fluoroquinolone antibiotic, ofloxacin, with titanium oxide
      nanoparticles in water: adsorption and breakdown.
AB  - The mobility and fate of fluoroquinolone antibiotics in natural waters, soil
      water systems and wastewater are controlled in part by surface interactions with
      nanometer (10-9 m) metal oxide particles. Experiments were performed by mixing
      solutions of ofloxacin (OFL), a common, fluoroquinolone-class human and
      veterinary antibiotic, with 25 nm-TiO2 (anatase) nanoparticles at different pH
      conditions. Both sorption and degradation of OFL were observed in the drug
      nanoparticle solutions with initial OFL concentrations of ~3 to 690 MUM. Though
      overall isotherm behavior is logarithmic, OFL removal from the solution can be
      approximated by linear removal coefficients (K(r)). At pH 4, K(r)=42+/-8 L kg-1,
      at pH 6 K(r)=1288+/-217 L kg-1, and at pH 9 K(r)=26+/-7 L kg-1. Rinsing of
      substrates at pH 4 resulted in desorption of approximately 11% of the original
      OFL removed from the solution by TiO2 nanoparticles. Less than 1% of the removed
      OFL at pH 6 was recovered by rinsing the substrate; and, at pH 9 about 39% of the
      OFL removed by nanoparticles during the initial mixing experiment was desorbed
      during rinsing. Mass spectral analysis of OFL solutions after the removal of the
      solid nanoparticles yielded ions that indicate the presence of de-methylated and
      de-carboxylated fluoroquinolone species, resulting from the degradation of OFL at
      the TiO2 surface.

PMID- 23134765
TI  - Land application of aerobic sewage sludge does not impair methane oxidation rates
      of soils.
AB  - The aim of this study was to measure and compare methane oxidation rates of
      arable and grassland soils that received 7.5t ha-1 y-1 of noncontaminated
      aerobically treated sewage sludge for ten years. Arable soils showed generally
      lower methane oxidation rates (from 6 to 15*10-3 h-1) than grassland soils (from
      26 to 33*103 h-1). Oxidation rate constants (k) of soils amended with sewage
      sludge were remarkably close to their respective untreated controls, but a soil,
      that had received a tenfold sewage sludge application (i.e. 75 t ha-1 y-1),
      showed a statistically significantly higher k-value. Laboratory addition of up to
      1000 mg Pb g-1 soil to this soil did not cause any significant change in methane
      oxidation, but caused a decrease from 13.9 to 10.9*10-3 h-1 in the control soil.
      Addition of Zn was much more toxic than Pb, with a significant decrease at 300
      MUg g-1 soil rate and an almost complete inhibition at 1500 MUg g-1 soil rate.
      Higher resistance was evident of sewage sludge treated soil in comparison to
      control soil, for both biomass C and CH4 oxidation activity.

PMID- 23134766
TI  - Constructed wetlands, 1991-2011: a review of research development, current
      trends, and future directions.
AB  - This study explores a bibliometric approach to quantitatively evaluate global
      scientific constructed wetlands research, and statistically assess current
      trends, and future directions using the Science Citation Index Expanded (SCI
      EXPANDED) database from 1991 to 2011. Articles referencing constructed wetlands
      were analyzed by accessing the following: publication language, output
      characteristics, publication performance by country and institution, author
      keywords, title words, and KeyWords Plus. Synthetically analyzing three keyword
      types, we concluded that the dominant constructed wetlands research hotspots from
      1991 to 2011 included water, nutrients, plants, and flow. These four hotspots
      remained the most dominant research areas throughout our study period, and are
      predicted to remain the top research emphases in the near future. "Soil" also
      exhibited a notable increase since 2005, and is likely to become another notable
      area of research interest in the future. "Phytoremediation" and "horizontal" were
      not identified in 1991-1995, but exhibited marked increases from 136th (0.5%) and
      169th (0.7%) in 1996-2000, to 9th (3.8%) and 11th (4.3%) in 2006-2011,
      respectively. Therefore, given the heightened attention during the last 15 years,
      these topics are likely to become a primary research focus in upcoming years.

PMID- 23134767
TI  - Air temperature-related human health outcomes: current impact and estimations of
      future risks in Central Italy.
AB  - The association between air temperature and human health is described in detail
      in a large amount of literature. However, scientific publications estimating how
      climate change will affect the population's health are much less extensive. In
      this study current evaluations and future predictions of the impact of
      temperature on human health in different geographical areas have been carried
      out. Non-accidental mortality and hospitalizations, and daily average air
      temperatures have been obtained for the 1999-2008 period for the ten main cities
      in Tuscany (Central Italy). High-resolution city-specific climatologic A1B
      scenarios centered on 2020 and 2040 have been assessed. Generalized additive and
      distributed lag models have been used to identify the relationships between
      temperature and health outcomes stratified by age: general adults (<65), elderly
      (aged 65-74) and very elderly (>=75). The cumulative impact (over a lag-period of
      30 days) of the effects of cold and especially heat, was mainly significant for
      mortality in the very elderly, with a higher impact on coastal plain than inland
      cities: 1  degrees C decrease/increase in temperature below/above the threshold
      was associated with a 2.27% (95% CI: 0.17-4.93) and 15.97% (95% CI: 7.43-24.51)
      change in mortality respectively in the coastal plain cities. A slight unexpected
      increase in short-term cold-related mortality in the very elderly, with respect
      to the baseline period, is predicted for the following years in half of the
      cities considered. Most cities also showed an extensive predicted increase in
      short-term heat-related mortality and a general increase in the annual
      temperature-related elderly mortality rate. These findings should encourage
      efforts to implement adaptation actions conducive to policy-making decisions,
      especially for planning short- and long-term health intervention strategies and
      mitigation aimed at preventing and minimizing the consequences of climate change
      on human health.

PMID- 23134768
TI  - Levels of polychlorinated dibenzo-p-dioxins, dibenzofurans and dioxin-like
      polychlorinated biphenyls in placentas from the Spanish INMA birth cohort study.
AB  - Because fetuses are considered significantly more sensitive to various
      environment toxicants, there is a need for continuous biomonitoring of
      polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and dioxin-like
      polychlorinated biphenyls PCBs (DL-PCBs) to assess their impact on this
      susceptible population. The aim of this study was to assess the concentration of
      PCDD/Fs and DL-PCBs in placenta samples from women participating in the Spanish
      Environment and Childhood (INMA) birth cohort study and to evaluate whether
      maternal and child characteristics predict placenta concentrations of these
      pollutants. The presence of PCDD/Fs and DL-PCBs was investigated in 50 placenta
      samples selected at random in the recruitment period 2000-2008. Multivariable
      regression models were constructed. Mothers had a mean age at delivery of 30.7
      years (18.0-38.0 years), pre-pregnancy BMI of 23.3 kg/m2 (18.0-40.2 kg/m2), and
      31% were smokers. Median total concentrations of PCDD/Fs and DL-PCBs were 6.9 pg
      WHO-TEQ/g lipid and 2.1 pg WHO-TEQ/g lipid, respectively. In comparison to the
      few previous studies in placenta, total TEQ levels were among the lowest recorded
      in comparable general populations. The congener distribution pattern and the
      frequencies and concentrations of PCDD/F and DL-PCB congeners were similar to
      previous reports in placenta. PCDD/F and DL-PCB exposure was related to the age
      of the mother and the year of the delivery. Although placental concentrations
      cannot be considered wholly appropriate predictors for evaluating fetal exposure
      to these contaminants, they can provide a good indication of both maternal and
      infant prenatal and postnatal exposure and can be used as a proxy for fetal
      exposure.

PMID- 23134769
TI  - Seasonal changes in organotin compounds in water and sediment samples from the
      semi-closed Port of Gdynia.
AB  - The effect of seasonal changes on the distribution of organotin compounds (OTC)
      in the sediments and seawater from the docks of the Port of Gdynia was
      investigated. Sediment and seawater samples were collected from four industrial
      docks in February (winter) and June (summer) in 2009. The samples were analyzed
      for butyltin, phenyltin, octyltin, and tricyclohexyltin (total of 9 OTC
      derivatives). The fine fraction (<0.063 mm) accumulated the highest concentration
      of OTC, although it was not the dominant fraction in the sediment samples from
      the Port of Gdynia. The average concentration of TBT, DBT and MBT in collected
      samples were as follows: 4400; 2188; 730 ng cation g-1 d.w. (February) 3638;
      1590; 474 ng cation g-1 d.w. (June) in the fine sediment samples, 2805; 1266; 485
      ng cation g-1 d.w. (February) in <2.00 mm sediment fractions and 118.6; 39.2;
      25.3 ng cation L-1 (February) and 46.5; 12.6; 8.2 ng cation L-1 (June) in the
      water samples. Higher concentrations of butyltin derivatives (BT) were observed
      in samples collected in February than in those collected in June. Seasonal
      changes in BT correlate well with changes in the water pH and concentrations of
      organic matter and can be attributed to sorption/desorption to sediments,
      photodegradation and biodegradation. Although the Port of Gdynia does not
      represent the natural features of a marine environment, seasonal variations
      recorded in the pH values as well as BT, organic carbon and biogenic element
      concentrations seem to be influenced by temperature and microbial activity.

PMID- 23134770
TI  - Regional hospital solid waste assessment using the evidential reasoning approach.
AB  - Hospital solid waste assessment is regularly characterized by a large number of
      known criteria that are both qualitative and quantitative in nature. The
      qualitative criteria can only be assessed by human judgments, which predictably
      engage a variety of uncertainties such as fuzziness and ignorance. Therefore,
      hospital solid waste assessments need to be analyzed and modeled using approaches
      that can handle uncertainties. The evidential reasoning (ER) approach can be
      utilized for such an analysis. In this paper, perhaps for the first time, the ER
      approach is applied to regional hospital solid waste assessment. The assessment
      criteria are characterized by a set of assessment grades assumed to be commonly
      exclusive and communally exhaustive. All assessment information, incomplete or
      complete, qualitative or quantitative, and imprecise or precise, are modeled
      using a cohesive belief structure. The ER approach will be used to aggregate
      multiple hospital solid waste assessment criteria, resulting in distributed
      assessment for each alternative. The proposed methodology is applied for regional
      hospital solid waste assessment in the province of Khuzestan, Iran.

PMID- 23134771
TI  - High mobility group AT-hook 2 is overexpressed in hepatoblastoma.
AB  - Hepatoblastoma is the most frequent malignant hepatic tumor in children.
      Expression of high mobility group AT-hook 2, an architectural nuclear factor and
      marker for hepatic progenitor cells, has not been studied in detail in
      hepatocellular neoplasms. Immunohistochemical stains using antibodies against
      high mobility group AT-hook 2, beta-catenin, glypican-3, p53, and Ki-67 were
      performed in 15 hepatoblastomas, 15 fibrolamellar hepatocellular carcinomas, 34
      hepatocellular carcinomas (12, <=30 years old; 22, >30 years old), and 22 hepatic
      adenomas. High mobility group AT-hook 2 was expressed in all 15 hepatoblastomas,
      including all fetal and embryonal components, significantly higher than in 41.7%
      (5/12) of hepatocellular carcinomas of 30 years or younger (P = .001) and in 9%
      (2/22) of hepatocellular carcinomas of older than 30 years (P < .001). Aberrant
      beta-catenin expression was detected in 80% (12/15) of hepatoblastomas, 41.6%
      (5/12) of hepatocellular carcinomas of 30 years or younger, and 18.2% (4/22) of
      hepatocellular carcinomas of older than 30 years. All 15 fibrolamellar
      hepatocellular carcinomas and 22 hepatic adenomas were negative for high mobility
      group AT-hook 2 or beta-catenin. High mobility group AT-hook 2 and beta-catenin
      expression correlated positively (P = .017; tau = 0.522) in 34 hepatocellular
      carcinomas. beta-Catenin and glypican-3 exhibited a distinct spatial distribution
      within hepatoblastomas; glypican-3 was more frequently expressed in fetal
      components (P = .007), whereas beta-catenin tended to be more frequently
      expressed in embryonal components (P = .062). In conclusion, high mobility group
      AT-hook 2 is expressed in all hepatoblastomas and could be used as a sensitive
      marker in their diagnosis. High mobility group AT-hook 2 was also expressed in a
      subset of hepatocellular carcinomas in association with beta-catenin expression;
      this might represent a subtype of hepatocellular carcinoma with hepatic
      progenitor cell differentiation.

PMID- 23134772
TI  - Hilar cholangiocarcinoma and pancreatic ductal adenocarcinoma share similar
      histopathologies, immunophenotypes, and development-related molecules.
AB  - Embryologically, intrahepatic small bile ducts arise from hepatic progenitor
      cells via ductal plates, whereas the pancreato-extrahepatic biliary progenitor
      cells expressing the transcription factors PDX1 and HES1 are reportedly involved
      in the development of the extrahepatic biliary tract and ventral pancreas. The
      expression of cellular markers characteristic of the different anatomical levels
      of the biliary tree and pancreas, as well as PDX1 and HES1, was examined in
      cholangiocarcinoma components of combined hepatocellular cholangiocarcinoma (12
      cases), intrahepatic cholangiocarcinoma (21 cases), hilar cholangiocarcinoma (25
      cases), and pancreatic ductal adenocarcinoma (18 cases). Anterior gradient
      protein-2 and S100P were frequently expressed in hilar cholangiocarcinoma and
      pancreatic ductal adenocarcinoma, whereas neural cell adhesion molecule and
      luminal expression of epithelial membrane antigen were common in
      cholangiocarcinoma components of combined hepatocellular cholangiocarcinoma. PDX1
      and HES1 were frequently and markedly expressed in pancreatic ductal
      adenocarcinoma and, to a lesser degree, in hilar cholangiocarcinoma, although
      their expression was rare and mild in cholangiocarcinoma components in combined
      hepatocellular cholangiocarcinoma. The expression patterns of these molecules in
      intrahepatic cholangiocarcinoma were intermediate between those in hilar
      cholangiocarcinoma and cholangiocarcinoma components of combined hepatocellular
      cholangiocarcinoma. Pancreatic ductal adenocarcinoma and hilar cholangiocarcinoma
      had a similar expression of mucin, immunophenotypes, as well as transcription
      factors. Pancreatic ductal adenocarcinoma and hilar cholangiocarcinoma showed
      similar postoperative prognosis. In conclusion, the similar expression of
      phenotypes related to pancreatobiliary anatomy and embryology may in part explain
      why these 2 types of carcinoma present similar clinicopathologic features.
      Further studies on the carcinogenesis of these carcinomas based on their
      similarities are warranted.

PMID- 23134773
TI  - In search of noise-induced bimodality.
AB  - Many biological studies are carried out on large populations of cells, often in
      order to obtain enough material to make measurements. However, we now know that
      noise is endemic in biological systems and this results in cell-to-cell
      variability in what appears to be a population of identical cells. Although often
      neglected, this noise can have a dramatic effect on system responses to
      environmental cues with significant and often counter-intuitive biological
      outcomes. A recent study in BMC Systems Biology provides an example of this,
      documenting a bimodal distribution of activated extracellular signal-regulated
      kinase in a population of cells exposed to epidermal growth factor and
      demonstrating that the observed bimodality of the response is induced purely by
      noise.

PMID- 23134774
TI  - A model of estrogen-related gene expression reveals non-linear effects in
      transcriptional response to tamoxifen.
AB  - BACKGROUND: Estrogen receptors alpha (ER) are implicated in many types of female
      cancers, and are the common target for anti-cancer therapy using selective
      estrogen receptor modulators (SERMs, such as tamoxifen). However, cell-type
      specific and patient-to-patient variability in response to SERMs (from
      suppression to stimulation of cancer growth), as well as frequent emergence of
      drug resistance, represents a serious problem. The molecular processes behind
      mixed effects of SERMs remain poorly understood, and this strongly motivates
      application of systems approaches. In this work, we aimed to establish a
      mathematical model of ER-dependent gene expression to explore potential
      mechanisms underlying the variable actions of SERMs. RESULTS: We developed an
      equilibrium model of ER binding with 17beta-estradiol, tamoxifen and DNA, and
      linked it to a simple ODE model of ER-induced gene expression. The model was
      parameterised on the broad range of literature available experimental data, and
      provided a plausible mechanistic explanation for the dual agonism/antagonism
      action of tamoxifen in the reference cell line used for model calibration. To
      extend our conclusions to other cell types we ran global sensitivity analysis and
      explored model behaviour in the wide range of biologically plausible parameter
      values, including those found in cancer cells. Our findings suggest that
      transcriptional response to tamoxifen is controlled in a complex non-linear way
      by several key parameters, including ER expression level, hormone concentration,
      amount of ER-responsive genes and the capacity of ER-tamoxifen complexes to
      stimulate transcription (e.g. by recruiting co-regulators of transcription). The
      model revealed non-monotonic dependence of ER-induced transcriptional response on
      the expression level of ER, that was confirmed experimentally in four variants of
      the MCF-7 breast cancer cell line. CONCLUSIONS: We established a minimal
      mechanistic model of ER-dependent gene expression, that predicts complex non
      linear effects in transcriptional response to tamoxifen in the broad range of
      biologically plausible parameter values. Our findings suggest that the outcome of
      a SERM's action is defined by several key components of cellular micro
      environment, that may contribute to cell-type-specific effects of SERMs and
      justify the need for the development of combinatorial biomarkers for more
      accurate prediction of the efficacy of SERMs in specific cell types.

PMID- 23134776
TI  - Trigger finger caused by anatomical variation lumbrical muscle.

PMID- 23134775
TI  - Assessing the gain of biological data integration in gene networks inference.
AB  - BACKGROUND: A current challenge in gene annotation is to define the gene function
      in the context of the network of relationships instead of using single genes. The
      inference of gene networks (GNs) has emerged as an approach to better understand
      the biology of the system and to study how several components of this network
      interact with each other and keep their functions stable. However, in general
      there is no sufficient data to accurately recover the GNs from their expression
      levels leading to the curse of dimensionality, in which the number of variables
      is higher than samples. One way to mitigate this problem is to integrate
      biological data instead of using only the expression profiles in the inference
      process. Nowadays, the use of several biological information in inference methods
      had a significant increase in order to better recover the connections between
      genes and reduce the false positives. What makes this strategy so interesting is
      the possibility of confirming the known connections through the included
      biological data, and the possibility of discovering new relationships between
      genes when observed the expression data. Although several works in data
      integration have increased the performance of the network inference methods, the
      real contribution of adding each type of biological information in the obtained
      improvement is not clear. METHODS: We propose a methodology to include biological
      information into an inference algorithm in order to assess its prediction gain by
      using biological information and expression profile together. We also evaluated
      and compared the gain of adding four types of biological information: (a) protein
      protein interaction, (b) Rosetta stone fusion proteins, (c) KEGG and (d) KEGG+GO.
      RESULTS AND CONCLUSIONS: This work presents a first comparison of the gain in the
      use of prior biological information in the inference of GNs by considering the
      eukaryote (P. falciparum) organism. Our results indicates that information based
      on direct interaction can produce a higher improvement in the gain than data
      about a less specific relationship as GO or KEGG. Also, as expected, the results
      show that the use of biological information is a very important approach for the
      improvement of the inference. We also compared the gain in the inference of the
      global network and only the hubs. The results indicates that the use of
      biological information can improve the identification of the most connected
      proteins.

PMID- 23134777
TI  - A three-dimensional analysis of osteoarthritic changes in the thumb
      carpometacarpal joint.
AB  - The purpose of this study is to gain a better understanding of the changes due to
      osteoarthritis (OA) occurring in the thumb carpometacarpal (CMC) joint by
      comparing quantitative geometrical measurements in computed tomography scans of
      healthy and pathological joints in various stages of OA. The measurements were
      (1) the subluxation of the metacarpal on the trapezium, (2) distance from the
      scaphoid centre to the metacarpal base, and (3) distance from the metacarpal base
      to the articulating surface of the trapezium. The three-dimensional position of
      three characteristic points on the metacarpal, trapezium, and scaphoid were
      detected in each of the 90 wrists we scanned. The distances between the points
      were compared by statistical analysis. With high accuracy, we have been able to
      confirm and quantify that subluxation occurs in the dorso-radial direction. A
      significant difference in trapezium height and joint space width was found
      between the OA and control groups. The results indicate how to restore the centre
      of rotation in surgical treatment of OA with total joint arthroplasty, but the
      clinical relevance of these findings has to be tested in further clinical
      studies. 

PMID- 23134778
TI  - Biomechanical assessment of a novel tendon junction.
AB  - The Pulvertaft weave has been the standard tendon junction technique used both in
      tendon transfers and tendon grafts. A limitation of this repair is the sequential
      failure of stabilizing sutures, rather than the tendon. A novel loop weave is
      described and compared with the Pulvertaft weave in biomechanical performance.
      Ovine deep flexor and extensor tendons were used to simulate Pulvertaft or loop
      weaves (n = 11) for tensile testing. The Pulvertaft weaves failed at the
      stabilizing sutures, whereas the loop weaves repairs failed by longitudinal
      splitting of the motor tendon. The loop weave demonstrated significantly higher
      mean initial failure and ultimate strengths. Tensile loads required to elongate
      the loop weave by 4, 6, and 8 mm were significantly higher, while more
      displacement was associated with the Pulvertaft repair under the application of
      50, 75, and 100 N tensile loads. This study demonstrates favourable biomechanical
      characteristics of the new loop weave technique. 

PMID- 23134779
TI  - Low prevalence of connexin-40 gene variants in atrial tissues and blood from
      atrial fibrillation subjects.
AB  - BACKGROUND: The atrial gap junction protein connexin-40 (Cx40) has been
      implicated to play an important role in atrial conduction and development of
      atrial fibrillation (AF). However, the frequency of Cx40 mutations in AF
      populations and their impact on Cx40 expression remains unclear. In this study,
      we sought to identify polymorphisms in the Cx40 gene GJA5, investigate the
      potential functional role of these polymorphisms, and determine their allelic
      frequencies. The prevalence of nonsynonymous Cx40 mutations in blood and atrial
      tissue was also compared to mutation frequencies reported in prior studies.
      METHODS: We conducted direct sequencing of the GJA5 coding and 3' UTR regions in
      blood samples from 91 lone AF subjects and 67 atrial tissue-derived samples from
      a lone cohort, a mixed AF cohort, and several transplant donors. Reporter gene
      transfection and tissue allelic expression imbalance assays were used to assess
      the effects of a common insertion/deletion polymorphism on Cx40 mRNA stability
      and expression. RESULTS: We identified one novel synonymous SNP in blood-derived
      DNA from a lone AF subject. In atrial tissue-derived DNA from lone and mixed AF
      subjects, we observed one novel nonsynonymous SNP, one rare previously reported
      synonymous SNP, and one novel 3' UTR SNP. A previously noted 25 bp
      insertion/deletion polymorphism in the 3' UTR was found to be common (minor
      allele frequency = 0.45) but had no effect on Cx40 mRNA stability and expression.
      The observed prevalence of nonsynonymous Cx40 mutations in atrial tissues derived
      from lone AF subjects differed significantly (p = 0.03) from a prior atrial
      tissue study reporting a high mutation frequency in a group of highly selected
      young lone AF subjects. CONCLUSIONS: Our results suggest that Cx40 coding SNPs
      are uncommon in AF populations, although rare mutations in this gene may
      certainly lead to AF pathogenesis. Furthermore, a common insertion/deletion
      polymorphism in the Cx40 3' UTR does not appear to play a role in modulating Cx40
      mRNA levels.

PMID- 23134781
TI  - House finches (Carpodacus mexicanus) balance investment in behavioural and
      immunological defences against pathogens.
AB  - Infection with parasites and pathogens is costly for hosts, causing loss of
      nutritional resources, reproductive potential, tissue integrity and even life. In
      response, animals have evolved behavioural and immunological strategies to avoid
      infection by pathogens and infestation by parasites. Scientists generally study
      these strategies in isolation from each other; however, since these defences
      entail costs, host individuals should benefit from balancing investment in these
      strategies, and understanding of infectious disease dynamics would benefit from
      studying the relationship between them. Here, we show that Carpodacus mexicanus
      (house finches) avoid sick individuals. Moreover, we show that individuals
      investing less in behavioural defences invest more in immune defences. Such
      variation has important implications for the dynamics of pathogen spread through
      populations, and ultimately the course of epidemics. A deeper understanding of
      individual- and population-level disease defence strategies will improve our
      ability to understand, model and predict the outcomes of pathogen spread in
      wildlife.

PMID- 23134780
TI  - Methods for high-throughput MethylCap-Seq data analysis.
AB  - BACKGROUND: Advances in whole genome profiling have revolutionized the cancer
      research field, but at the same time have raised new bioinformatics challenges.
      For next generation sequencing (NGS), these include data storage, computational
      costs, sequence processing and alignment, delineating appropriate statistical
      measures, and data visualization. Currently there is a lack of workflows for
      efficient analysis of large, MethylCap-seq datasets containing multiple sample
      groups. METHODS: The NGS application MethylCap-seq involves the in vitro capture
      of methylated DNA and subsequent analysis of enriched fragments by massively
      parallel sequencing. The workflow we describe performs MethylCap-seq experimental
      Quality Control (QC), sequence file processing and alignment, differential
      methylation analysis of multiple biological groups, hierarchical clustering,
      assessment of genome-wide methylation patterns, and preparation of files for data
      visualization. RESULTS: Here, we present a scalable, flexible workflow for
      MethylCap-seq QC, secondary data analysis, tertiary analysis of multiple
      experimental groups, and data visualization. We demonstrate the experimental QC
      procedure with results from a large ovarian cancer study dataset and propose
      parameters which can identify problematic experiments. Promoter methylation
      profiling and hierarchical clustering analyses are demonstrated for four groups
      of acute myeloid leukemia (AML) patients. We propose a Global Methylation
      Indicator (GMI) function to assess genome-wide changes in methylation patterns
      between experimental groups. We also show how the workflow facilitates data
      visualization in a web browser with the application Anno-J. CONCLUSIONS: This
      workflow and its suite of features will assist biologists in conducting
      methylation profiling projects and facilitate meaningful biological
      interpretation.

PMID- 23134782
TI  - Passive rafting is a powerful driver of transoceanic gene flow.
AB  - Dispersal by passive oceanic rafting is considered important for the assembly of
      biotic communities on islands. However, not much is known about levels of
      population genetic connectivity maintained by rafting over transoceanic
      distances. We assess the evolutionary impact of kelp-rafting by estimating
      population genetic differentiation in three kelp-associated invertebrate species
      across a system of islands isolated by oceanic gaps for over 5 million years,
      using mtDNA and AFLP markers. The species occur throughout New Zealand's
      subantarctic islands, but lack pelagic stages and any opportunity for
      anthropogenic transportation, and hence must rely on passive rafting for long
      distance dispersal. They all have been directly observed to survive transoceanic
      kelp-rafting journeys in this region. Our analyses indicate that regular gene
      flow occurs among populations of all three species between all of the islands,
      especially those on either side of the subtropical front oceanographic boundary.
      Notwithstanding its perceived sporadic nature, long-distance kelp-rafting appears
      to enable significant gene flow among island populations separated by hundreds of
      kilometres of open ocean.

PMID- 23134783
TI  - A low trophic position of Japanese eel larvae indicates feeding on marine snow.
AB  - What eel larvae feed on in the surface layer of the ocean has remained
      mysterious. Gut contents and bulk nitrogen stable isotope studies suggested that
      these unusual larvae, called leptocephali, feed at a low level in the oceanic
      food web, whereas other types of evidence have suggested that small zooplankton
      are eaten. In this study, we determined the nitrogen isotopic composition of
      amino acids of both natural larvae and laboratory-reared larvae of the Japanese
      eel to estimate the trophic position (TP) of leptocephali. We observed a mean TP
      of 2.4 for natural leptocephali, which is consistent with feeding on particulate
      organic matter (POM) such as marine snow and discarded appendicularian houses
      containing bacteria, protozoans and other biological materials. The nitrogen
      isotope enrichment values of the reared larvae confirm that the primary food
      source of natural larvae is consistent only with POM. This shows that
      leptocephali feed on readily available particulate material originating from
      various sources closely linked to ocean primary production and that leptocephali
      are a previously unrecognized part of oceanic POM cycling.

PMID- 23134784
TI  - Ecological niche structure and rangewide abundance patterns of species.
AB  - Spatial abundance patterns across species' ranges have attracted intense
      attention in macroecology and biogeography. One key hypothesis has been that
      abundance declines with geographical distance from the range centre, but tests of
      this idea have shown that the effect may occur indeed only in a minority of
      cases. We explore an alternative hypothesis: that species' abundances decline
      with distance from the centroid of the species' habitable conditions in
      environmental space (the ecological niche). We demonstrate consistent negative
      abundance-ecological distance relationships across all 11 species analysed
      (turtles to wolves), and that relationships in environmental space are
      consistently stronger than relationships in geographical space.

PMID- 23134785
TI  - Ecological modelling, size distributions and taphonomic size bias in dinosaur
      faunas: a comment on Codron et al. (2012).

PMID- 23134787
TI  - Healing Narrative-Ethics and Writing about Patients.

PMID- 23134788
TI  - Case studies and the therapeutic relationship.

PMID- 23134789
TI  - Ethics, memoir, and medicine.

PMID- 23134786
TI  - LRF-mediated Dll4 repression in erythroblasts is necessary for hematopoietic stem
      cell maintenance.
AB  - Hematopoietic stem cells (HSCs) are the most primitive cells in the hematopoietic
      system and are under tight regulation for self-renewal and differentiation. Notch
      signals are essential for the emergence of definitive hematopoiesis in mouse
      embryos and are critical regulators of lymphoid lineage fate determination.
      However, it remains unclear how Notch regulates the balance between HSC self
      renewal and differentiation in the adult bone marrow (BM). Here we report a novel
      mechanism that prevents HSCs from undergoing premature lymphoid differentiation
      in BM. Using a series of in vivo mouse models and functional HSC assays, we show
      that leukemia/lymphoma related factor (LRF) is necessary for HSC maintenance by
      functioning as an erythroid-specific repressor of Delta-like 4 (Dll4) expression.
      Lrf deletion in erythroblasts promoted up-regulation of Dll4 in erythroblasts,
      sensitizing HSCs to T-cell instructive signals in the BM. Our study reveals novel
      cross-talk between HSCs and erythroblasts, and sheds a new light on the
      regulatory mechanisms regulating the balance between HSC self-renewal and
      differentiation.

PMID- 23134790
TI  - Anonymous physician blogging.

PMID- 23134791
TI  - 2010 winning essay:social (networking) justice.

PMID- 23134792
TI  - 2010 runner-up essay:social roles and semi-public spaces on the internet-the case
      of jason and emily.

PMID- 23134793
TI  - 2010 Runner-Up Essay:Jason's Journal-Thoughts of an Ethically Conflicted Medical
      Student.

PMID- 23134794
TI  - Medical Students Learn to Tell Stories about Their Patients and Themselves.

PMID- 23134795
TI  - Multiple exposures-reflective writing in the first year of medical school.

PMID- 23134796
TI  - The AMA Code of Medical Ethics' Opinions on Confidentiality of Patient
      Information.

PMID- 23134798
TI  - The art of writing patient record notes.

PMID- 23134797
TI  - The poetry of john stone, MD.

PMID- 23134799
TI  - When Doctors Pick up the Pen-Patient-Doctor Confidentiality Breaches in
      Publishing.

PMID- 23134800
TI  - A delicate balance-ethical standards for physician-journalists.

PMID- 23134801
TI  - Vulnerability in physicians' narratives.

PMID- 23134802
TI  - The house of god-is it pertinent 30 years later?

PMID- 23134803
TI  - The case history and deferred pain.

PMID- 23134804
TI  - About the contributors.

PMID- 23134805
TI  - Some southern African plant species used to treat helminth infections in
      ethnoveterinary medicine have excellent antifungal activities.
AB  - BACKGROUND: Diseases caused by microorganisms and parasites remain a major
      challenge globally and particularly in sub-Saharan Africa to man and livestock.
      Resistance to available antimicrobials and the high cost or unavailability of
      antimicrobials complicates matters. Many rural people use plants to treat these
      infections. Because some anthelmintics e.g. benzimidazoles also have good
      antifungal activity we examined the antifungal activity of extracts of 13 plant
      species used in southern Africa to treat gastrointestinal helminth infections in
      livestock and in man. METHODS: Antifungal activity of acetone leaf extracts was
      determined by serial microdilution with tetrazolium violet as growth indicator
      against Aspergillus fumigatus, Cryptococcus neoformans and Candida albicans.
      These pathogens play an important role in opportunistic infections of immune
      compromised patients. Cytotoxicity was determined by MTT cellular assay.
      Therapeutic indices were calculated and selectivity for different pathogens
      determined. We proposed a method to calculate the relation between microbicidal
      and microbistatic activities. Total activities for different plant species were
      calculated. RESULTS: On the whole, all 13 extracts had good antifungal activities
      with MIC values as low as 0.02 mg/mL for extracts of Clausena anisata against
      Aspergillus fumigatus and 0.04 mg/mL for extracts of Zanthoxylum capense,
      Clerodendrum glabrum, and Milletia grandis, against A. fumigatus. Clausena
      anisata extracts had the lowest cytotoxicity (LC50) of 0.17 mg/mL, a reasonable
      therapeutic index (2.65) against A. fumigatus. It also had selective activity
      against A. fumigatus, an overall fungicidal activity of 98% and a total activity
      of 3395 mL/g against A. fumigatus. This means that 1 g of acetone leaf extract
      can be diluted to 3.4 litres and it would still inhibit the growth. Clerodendrum
      glabrum, Zanthoxylum capense and Milletia grandis extracts also yielded promising
      results. CONCLUSIONS: Some plant extracts used for treatment of parasitic
      infections also have good antifungal activity. Because it is much easier to
      isolate antifungal compounds by bioassay guided fractionation, this approach may
      facilitate the isolation of anthelmintic compounds from active plant extracts.
      The viability of this approach can be tested by isolating the antifungal
      compounds and then determining its anthelmintic activity. Some of these plant
      extracts may also be useful in combating fungal infections.

PMID- 23134806
TI  - A Steiner tree-based method for biomarker discovery and classification in breast
      cancer metastasis.
AB  - BACKGROUND: Metastatic breast cancer is a leading cause of cancer-related deaths
      in women worldwide. DNA microarray has become an important tool to help identify
      biomarker genes for improving the prognosis of breast cancer. Recently, it was
      shown that pathway-level relationships between genes can be incorporated to build
      more robust classification models and to obtain more useful biological insight
      from such models. Due to the unavailability of complete pathways, protein-protein
      interaction (PPI) network is becoming more popular to researcher and opens a new
      way to investigate the developmental process of breast cancer. METHODS: In this
      study, a network-based method is proposed to combine microarray gene expression
      profiles and PPI network for biomarker discovery for breast cancer metastasis.
      The key idea in our approach is to identify a small number of genes to connect
      differentially expressed genes into a single component in a PPI network; these
      intermediate genes contain important information about the pathways involved in
      metastasis and have a high probability of being biomarkers. RESULTS: We applied
      this approach on two breast cancer microarray datasets, and for both cases we
      identified significant numbers of well-known biomarker genes for breast cancer
      metastasis. Those selected genes are significantly enriched with biological
      processes and pathways related to cancer carcinogenic process, and, importantly,
      have much higher stability across different datasets than in previous studies.
      Furthermore, our selected genes significantly increased cross-data classification
      accuracy of breast cancer metastasis. CONCLUSIONS: The randomized Steiner tree
      based approach described in this study is a new way to discover biomarker genes
      for breast cancer, and improves the prediction accuracy of metastasis. Though the
      analysis is limited here only to breast cancer, it can be easily applied to other
      diseases.

PMID- 23134807
TI  - The effects of a Special Olympics Unified Sports Soccer training program on
      anthropometry, physical fitness and skilled performance in Special Olympics
      soccer athletes and non-disabled partners.
AB  - The study investigated the effects of a Special Olympics (SO) Unified Sport (UNS)
      soccer program on anthropometry, physical fitness and soccer skills of male youth
      athletes with and without intellectual disabilities (ID) who participated in a
      training group (TRG) and in a comparison group (CG) without specific training.
      Youth with ID (WID) were randomly selected out of all the students between the
      ages 12 and 15, with a diagnosis of educable mental retardation and no secondary
      disabilities, who were attending a special education school. Participants without
      ID (WoID) were randomly selected from a regular secondary school out of the same
      age groups of male students. All participants were given permission by their
      parents or guardians to participate in the study. Participants in the TRG
      included 23 youth WID and 23 youth WoID. Mean ages were = 14.1 (SD = 1.1) and
      13.2 (SD = 0.79) respectively. Fifteen WID, and 15 WoID comprised the CG. Mean
      ages were 14.51 (SD = 0.81) and 13.78 (SD = 0.49) respectively. Prior to and
      following the program measurements were conducted, and data were collected on
      students' anthropometric and fitness components of the Brockport physical fitness
      test as well as a soccer skill performance based on the SO soccer skill test.
      Participants in the TRG trained 8 weeks, 1.5h per session, three times per week,
      in an after-school soccer program. CG did not participate in any sports program
      outside of the school physical education class. Dependent t tests and effect size
      calculations revealed that SO athletes and non-disabled partners scored
      significantly higher with regard to physical fitness and football skills in most
      variables compared with their CG. This Unified Program was successful in
      increasing fitness and soccer skill performance of youth WID as well as of those
      WoID.

PMID- 23134808
TI  - Mechanical, physico-chemical, and antimicrobial properties of gelatin-based film
      incorporated with catechin-lysozyme.
AB  - BACKGROUND: Microbial activity is a primary cause of deterioration in many foods
      and is often responsible for reduced quality and safety. Food-borne illnesses
      associated with E. coli O157:H7, S. aureus, S. enteritidis and L. monocytogenes
      are a major public health concern throughout the world. A number of methods have
      been employed to control or prevent the growth of these microorganisms in food.
      Antimicrobial packaging is one of the most promising active packaging systems for
      effectively retarding the growth of food spoilage and pathogenic microorganisms.
      The aim of this study was to determine the mechanical, physico-chemical
      properties and inhibitory effects of the fish gelatin films against selected food
      spoilage microorganisms when incorporated with catechin-lysozyme. RESULTS: The
      effect of the catechin-lysozyme combination addition (CLC: 0, 0.125, 0.25, and
      0.5%, w/v) on fish gelatin film properties was monitored. At the level of 0.5%
      addition, the CLC showed the greatest elongation at break (EAB) at 143.17% with
      0.039 mm thickness, and the lowest water vapor permeability (WVP) at 6.5 x 10-8
      g.mm.h-1.cm-2.Pa-1, whereas the control showed high tensile strength (TS) and the
      highest WVP. Regarding color attributes, the gelatin film without CLC addition
      gave the highest lightness (L* 91.95) but lowest in redness (a*-1.29) and
      yellowness (b* 2.25) values. The light transmission of the film did not
      significantly decrease and nor did film transparency (p>0.05) with increased CLC.
      Incorporating CLC could not affect the film microstructure. The solubility of the
      gelatin based film incorporated with CLC was not affected, especially at a high
      level of addition (p>0.05). Inhibitory activity of the fish gelatin film against
      E.coli, S.aureus, L. innocua and S. cerevisiae was concentration dependent.
      CONCLUSIONS: These findings suggested that CLC incorporation can improve
      mechanical, physico-chemical, and antimicrobial properties of the resulting
      films, thus allowing the films to become more applicable in active food
      packaging.

PMID- 23134809
TI  - Evaluation of hemoculture extraction technique in an emergency department:
      nursing staff self-perception and reality.
AB  - INTRODUCTION: Between 2009 and 2010, the rate of contamination of hemocultures
      drawn in our emergency department was much higher than the quality standards
      recommended, so we decided to check the extraction procedure of the samples to
      detect possible faults. We also wanted to study the perception of the nursing
      staff about the quality of their practice. METHODS: This is a prospective study
      developed in 2 phases. In the first phase, medical staff observed the extraction
      of hemocultures. In the second phase, an anonymous test was sent to the nursing
      staff of the emergency department. RESULTS: We observed major faults in the
      extraction procedure. Of the 10 items checked, only 2 had a compliance rate
      greater than 50%. There were significant differences between test answers and
      data recovered from observation in 7 items. DISCUSSION: Several technical
      deficiencies were observed in the procedure for extraction of blood cultures.
      This fact partly explains the high rate of contamination found in our emergency
      department.

PMID- 23134810
TI  - Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced
      cardiac contractile dysfunction: role of oxidative stress and autophagy.
AB  - BACKGROUND: Lethal and edema toxins secreted by Bacillus anthracis during anthrax
      infection were found to incite serious cardiovascular complications. However, the
      underlying mechanisms in anthrax lethal toxin-induced cardiac anomalies remain
      unknown. This study was designed to evaluate the impact of antioxidant enzyme
      catalase in anthrax lethal toxin-induced cardiomyocyte contractile dysfunction.
      METHODS: Wild type (WT) and cardiac-specific catalase overexpression mice were
      challenged with lethal toxin (2 MUg/g, intraperotineally (i.p.)). Cardiomyocyte
      contractile and intracellular Ca(2+) properties were assessed 18 h later using an
      IonOptix edge-detection system. Proteasome function was assessed using
      chymotrypsin-like and caspase-like activities. GFP-LC3 puncta and Western blot
      analysis were used to evaluate autophagy and protein ubiquitination. RESULTS:
      Lethal toxin exposure suppressed cardiomyocyte contractile function (suppressed
      peak shortening, maximal velocity of shortening/re-lengthening, prolonged
      duration of shortening/re-lengthening, and impaired intracellular Ca(2+)
      handling), the effects of which were alleviated by catalase. In addition, lethal
      toxin triggered autophagy, mitochondrial and ubiquitin-proteasome defects, the
      effects of which were mitigated by catalase. Pretreatment of cardiomyocytes from
      catalase mice with the autophagy inducer rapamycin significantly attenuated or
      ablated catalase-offered protection against lethal toxin-induced cardiomyocyte
      dysfunction. On the other hand, the autophagy inhibitor 3-MA ablated or
      significantly attenuated lethal toxin-induced cardiomyocyte contractile
      anomalies. CONCLUSIONS: Our results suggest that catalase is protective against
      anthrax lethal toxin-induced cardiomyocyte contractile and intracellular Ca(2+)
      anomalies, possibly through regulation of autophagy and mitochondrial function.

PMID- 23134811
TI  - Comparison of 3 accelerometer data reduction approaches, step counts, and 2 self
      report measures for estimating physical activity in free-living adults.
AB  - BACKGROUND: Accelerometers have become one of the most common methods of
      measuring physical activity (PA). Thus, validity of accelerometer data reduction
      approaches remains an important research area. Yet, few studies directly compare
      data reduction approaches and other PA measures in free-living samples.
      OBJECTIVE: To compare PA estimates provided by 3 accelerometer data reduction
      approaches, steps, and 2 self-reported estimates: Crouter's 2-regression model,
      Crouter's refined 2-regression model, the weighted cut-point method adopted in
      the National Health and Nutrition Examination Survey (NHANES; 2003-2004 and 2005
      2006 cycles), steps, IPAQ, and 7-day PA recall. METHODS: A worksite sample (N =
      87) completed online-surveys and wore ActiGraph GT1M accelerometers and
      pedometers (SW-200) during waking hours for 7 consecutive days. Daily time spent
      in sedentary, light, moderate, and vigorous intensity activity and percentage of
      participants meeting PA recommendations were calculated and compared. RESULTS:
      Crouter's 2-regression (161.8 +/- 52.3 minutes/day) and refined 2-regression
      (137.6 +/- 40.3 minutes/day) models provided significantly higher estimates of
      moderate and vigorous PA and proportions of those meeting PA recommendations (91%
      and 92%, respectively) as compared with the NHANES weighted cut-point method
      (39.5 +/- 20.2 minutes/day, 18%). Differences between other measures were also
      significant. CONCLUSIONS: When comparing 3 accelerometer cut-point methods,
      steps, and self-report measures, estimates of PA participation vary
      substantially.

PMID- 23134813
TI  - Effect of tracheal suctioning on aspiration past the tracheal tube cuff in
      mechanically ventilated patients.
AB  - BACKGROUND: This clinical study evaluated the effect of a suctioning maneuver on
      aspiration past the cuff during mechanical ventilation. METHODS: Patients
      intubated for less than 48 hours with a PVC-cuffed tracheal tube, under
      mechanical ventilation with a PEEP >=5 cm H2O and under continuous sedation, were
      included in the study. At baseline the cuff pressure was set at 30 cm H2O. Then
      0.5ml of blue dye diluted with 3 ml of saline was instilled into the subglottic
      space just above the cuff. Tracheal suctioning was performed using a 16-French
      suction catheter with a suction pressure of - 400 mbar. A fiberoptic bronchoscopy
      was performed before and after the suctioning maneuver, looking for the presence
      of blue dye in the folds within the cuff wall or in the trachea under the cuff.
      The sealing of the cuff was defined by the absence of leakage of blue dye either
      in the cuff wall or in the trachea under the cuff. RESULTS: Twenty-five patients
      were included. The size of the tracheal tube was 7-mm ID for 5 patients, 7.5-mm
      ID for 16 patients, and 8-mm ID for four patients. Blue dye was never seen in the
      trachea under the cuff before suctioning and only in one patient (4%) after the
      suctioning maneuver. Blue dye was observed in the folds within the cuff wall in 6
      of 25 patients before suctioning and 11 of 25 after (p = 0.063). Overall, the
      incidence of sealing of the cuff was 76% before suctioning and 56% after (p =
      0.073). CONCLUSIONS: In patients intubated with a PVC-cuffed tracheal tube and
      under mechanical ventilation with PEEP >=5 cm H2O and a cuff pressure set at 30
      cm H2O, a single tracheal suctioning maneuver did not increase the risk of
      aspiration in the trachea under the cuff. TRIAL REGISTRATION: ClinicalTrials.gov,
      number NCT01170156.

PMID- 23134812
TI  - Treatment of medulloblastoma using an oncolytic measles virus encoding the
      thyroidal sodium iodide symporter shows enhanced efficacy with radioiodine.
AB  - BACKGROUND: Medulloblastoma is the most common malignant brain tumor of
      childhood. Although the clinical outcome for medulloblastoma patients has
      improved significantly, children afflicted with the disease frequently suffer
      from debilitating side effects related to the aggressive nature of currently
      available therapy. Alternative means for treating medulloblastoma are desperately
      needed. We have previously shown that oncolytic measles virus (MV) can
      selectively target and destroy medulloblastoma tumor cells in localized and
      disseminated models of the disease. MV-NIS, an oncolytic measles virus that
      encodes the human thyroidal sodium iodide symporter (NIS), has the potential to
      deliver targeted radiotherapy to the tumor site and promote a localized bystander
      effect above and beyond that achieved by MV alone. METHODS: We evaluated the
      efficacy of MV-NIS against medulloblastoma cells in vitro and examined their
      ability to incorporate radioiodine at various timepoints, finding peak uptake at
      48 hours post infection. The effects of MV-NIS were also evaluated in mouse
      xenograft models of localized and disseminated medulloblastoma. Athymic nude mice
      were injected with D283med-Luc medulloblastoma cells in the caudate putamen
      (localized disease) or right lateral ventricle (disseminated disease) and
      subsequently treated with MV-NIS. Subsets of these mice were given a dose of 131I
      at 24, 48 or 72 hours later. RESULTS: MV-NIS treatment, both by itself and in
      combination with 131I, elicited tumor stabilization and regression in the treated
      mice and significantly extended their survival times. Mice given 131I were found
      to concentrate radioiodine at the site of their tumor implantations. In addition,
      mice with localized tumors that were given 131I either 24 or 48 hours after MV
      NIS treatment exhibited a significant survival advantage over mice given MV-NIS
      alone. CONCLUSIONS: These data suggest MV-NIS plus radioiodine may be a
      potentially useful therapy for the treatment of medulloblastoma.

PMID- 23134814
TI  - Better access to general practice is linked to improved quality of care, finds
      analysis.

PMID- 23134815
TI  - Development and evaluation of a questionnaire to measure the perceived
      implementation of the mission statement of a competency based curriculum.
AB  - BACKGROUND: A mission statement (MS) sets out the long-term goals of an
      institution and is supposed to be suited for studying learning environments. Yet,
      hardly any study has tested this issue so far. The aim of the present study was
      the development and psychometric evaluation of an MS-Questionnaire (MSQ) focusing
      on explicit competencies. We investigated to what extent the MSQ captures the
      construct of learning environment and how well a faculty is following--in its
      perception--a competency orientation in a competency-based curriculum. METHODS: A
      questionnaire was derived from the MS "teaching" (Medical Faculty, Heinrich-Heine
      University Dusseldorf) which was based on (inter-) nationally accepted goals and
      recommendations for a competency based medical education. The MSQ was
      administered together with the Dundee Ready Education Environment Measure (DREEM)
      to 1119 students and 258 teachers. Cronbach's alpha was used to analyze the
      internal consistency of the items. Explorative factor analyses were performed to
      analyze homogeneity of the items within subscales and factorial validity of the
      MSQ. Item discrimination was assessed by means of part-whole corrected
      discrimination indices, and convergent validity was analyzed with respect to
      DREEM. Demographic variations of the respondents were used to analyze the inter
      group variations in their responses. RESULTS: Students and teachers perceived the
      MS implementation as "moderate" and on average, students differed significantly
      in their perception of the MS. They thought implementation of the MS was less
      successful than faculty did. Women had a more positive perception of educational
      climate than their male colleagues and clinical students perceived the
      implementation of the MS on all dimensions significantly worse than preclinical
      students. The psychometric properties of the MSQ were very satisfactory: Item
      discrimination was high. Similarly to DREEM, the MSQ was highly reliable among
      students (alpha = 0.92) and teachers (alpha = 0.93). In both groups, the MSQ
      correlated highly positively with DREEM (r = 0.79 and 0.80, p < 0.001 each).
      Factor analyses did not reproduce the three areas of the MS perfectly. The
      subscales, however, could be identified as such both among teachers and students.
      CONCLUSIONS: The perceived implementation of faculty-specific goals can be
      measured in an institution to some considerable extent by means of a
      questionnaire developed on the basis of the institution's MS. Our MSQ provides a
      reliable instrument to measure the learning climate with a strong focus on
      competencies which are increasingly considered crucial in medical education. The
      questionnaire thus offers additional information beyond the DREEM. Our site
      specific results imply that our own faculty is not yet fully living up to its
      competency-based MS. In general, the MSQ might prove useful for faculty
      development to the increasing number of faculties seeking to measure their
      perceived competency orientation in a competency-based curriculum.

PMID- 23134816
TI  - Boolean network inference from time series data incorporating prior biological
      knowledge.
AB  - BACKGROUND: Numerous approaches exist for modeling of genetic regulatory networks
      (GRNs) but the low sampling rates often employed in biological studies prevents
      the inference of detailed models from experimental data. In this paper, we
      analyze the issues involved in estimating a model of a GRN from single cell line
      time series data with limited time points. RESULTS: We present an inference
      approach for a Boolean Network (BN) model of a GRN from limited transcriptomic or
      proteomic time series data based on prior biological knowledge of connectivity,
      constraints on attractor structure and robust design. We applied our inference
      approach to 6 time point transcriptomic data on Human Mammary Epithelial Cell
      line (HMEC) after application of Epidermal Growth Factor (EGF) and generated a BN
      with a plausible biological structure satisfying the data. We further defined and
      applied a similarity measure to compare synthetic BNs and BNs generated through
      the proposed approach constructed from transitions of various paths of the
      synthetic BNs. We have also compared the performance of our algorithm with two
      existing BN inference algorithms. CONCLUSIONS: Through theoretical analysis and
      simulations, we showed the rarity of arriving at a BN from limited time series
      data with plausible biological structure using random connectivity and absence of
      structure in data. The framework when applied to experimental data and data
      generated from synthetic BNs were able to estimate BNs with high similarity
      scores. Comparison with existing BN inference algorithms showed the better
      performance of our proposed algorithm for limited time series data. The proposed
      framework can also be applied to optimize the connectivity of a GRN from
      experimental data when the prior biological knowledge on regulators is limited or
      not unique.

PMID- 23134817
TI  - Comparison of whole body diffusion weighted magnetic resonance imaging and
      somatostatin receptor scintigraphy for oncogenic osteomalacia.
AB  - OBJECTIVE: To compare the accuracy of whole body diffusion weighted magnetic
      resonance imaging (WB-DWI) with that of somatostatin receptor scintigraphy (SRS)
      in the detection and localization of the lesions in patients with oncogenic
      osteomalacia (OOM). METHODS: Totally 6 patients with clinically suspected
      oncogenic osteomalacia were enrolled. All of them underwent WB-DWI and SRS within
      2 weeks to evaluate the possible presence of tumors that lead to osteomalacia.
      Surgical and pathological findings were considered as the gold standard. The
      sensitivity, specificity, and accuracy were calculated. RESULTS: Pathology
      confirmed the diagnosis of two soft tissue tumors (including 1 angiolipoma and 1
      mesenchymal tumor) and one bone tumor of malignant neurofibroma. The sensitivity,
      specificity, and accuracy in the identification of lesions in patients with
      oncogenic osteomalacia were 33.33%, 100%, 66.67% for WB-DWI and 33.33%, 66.67%,
      50% for SRS (P>0.05). CONCLUSION: For adult patients with osteomalacia, WB-DWI
      and SRS can provide mutually supportive data and be used for identifying
      potential oncogenic osteomalacia.

PMID- 23134819
TI  - Voxel-based Relaxometry of transverse relaxation rate with gradient echo R2(*) in
      patients with multiple system atrophy.
AB  - OBJECTIVE: To explore the transverse relaxation rate with gradient echo R2(*)
      changes in patients with Parkinsonian variant of multiple system atrophy (MSA-P)
      with a voxel-based analysis of R2(*) map. METHODS: Whole brain structural images
      and multi-echo T2(*) weighted image were acquired in 27 patients with probable
      MSA-P and 24 healthy individuals. R2(*) maps of the MSA-P were compared with the
      controls by voxel-based methods. RESULT: Compared with the controls, MSA-P
      patients showed significant R2(*) decrease bilaterally in brain stem, cerebellar
      hemispheres, insular lobe, temporal lobes, caudate nucleus, and corpus callosum
      (P<0.005). CONCLUSIONS: R2(*) can reveal the significant brain involvements of
      MSA-P. The introduction of gradient echo may increase the sensitivity, although
      the susceptible artifact may interfere the detection efficiency of R2(*).

PMID- 23134818
TI  - Clinical use of magnetic resonance plaque imaging for intracranial arteries.
AB  - OBJECTIVE: To summarize the value and limitations of magnetic resonance (MR)
      plaque imaging for intracranial arteries. METHOD: The data of MR plaque imaging
      of intracranial arteries in 422 patients performed in Peking Union Medical
      College Hospital from December 2006 to September 2010 were analyzed
      retrospectively. RESULTS: The success rate for MR plaque imaging of intracranial
      arteries was 97%. MR plaque imaging clearly displayed the wall structure of the
      arteries trunk (M1 segment of middle cerebral arteries, M2-3 segment of anterior
      cerebral arteries, and basilar arteries). Good inter-observer (k=0.91, 95%
      CI=0.80-1.03) and intra-observer reproducibility (k=0.96,95% CI=0.88-1.03) was
      observed in the evaluation of middle cerebral arteries' atherosclerosis. The wall
      features had significant difference between symptomatic and asymptomatic
      intracranial arteries'stenosis; compared with asymptomatic middle cerebral artery
      stenosis(35 cases), symptomatic middle cerebral artery stenosis(26 cases) had a
      significantly larger wall area (P=0.000), greater remodeling ratio (P=0.000),
      higher prevalence of expansive remodeling (outward expansion of the vessel wall)
      (P=0.003), and lower prevalence of constrictive remodeling (P=0.008). Arteritis
      of middle cerebral artery (3 cases) showed circular wall-thickening with apparent
      gadolinium-diethylene triamine pentaacetic acid-biotin enhancement. CONCLUSION:
      The MR plaque imaging is helpful in the evaluation of intracranial arteries
      stenosis, although it still has the limitations such as short scan range and low
      resolution.

PMID- 23134820
TI  - Clinical application of magnetic resonance imaging in preoperative evaluation of
      endometrial cancer.
AB  - OBJECTIVE: To investigate the value of magnetic resonance imaging (MRI) in the
      preoperative assessment of endometrial cancer. METHODS: Ninety-four patients with
      histopathologically confirmed endometrial carcinoma were retrospectively enrolled
      in this study. MRI findings were compared with the pathologic findings in all
      cases. The depth of myometrial invasion and lymph node metastasis were evaluated
      by T2 weighted imaging (T2WI) combined with contrast enhancement or diffusion
      weighted imaging (DWI). RESULTS: Among these 94 patients,62 had no or superficial
      myometrial involvement and 32 cases had deep myometrial involvement. Meanwhile,
      24 groups of metastatic lymph nodes and 164 groups of non-metastatic lymph nodes
      were detected. The accuracy, specificity, sensitivity, negative predictive value,
      and positive predictive value of T2WI combined with contrast enhancement in
      discriminating no/superficial myometrial involvement from deep myometrial
      involvement were 88.3%, 90.3%, 84.4%, 91.8%, and 81.8%, whereas those of T2WI
      combined with DWI were 81.9%, 87.1%, 71.9%, 85.7%, and 74.2%, respectively. The
      accuracy, specificity, sensitivity, negative predictive value, and positive
      predictive value of T2WI combined with contrast enhancement in identifying
      metastatic lymph nodes were 89.4%, 96.8%, 54.5%, 90.9%, and 78.3%, whereas those
      of T2WI combined with DWI were 91.5%, 95.5%, 72.7%, 94.3%, and 77.4%,
      respectively. CONCLUSIONS: T2WI combined with contrast enhancement is superior to
      T2WI combined with DWI in evaluation of the depth of myometrial invasion.
      However, DWI is more sensitive in identifying lymph node metastasis than T2WI
      combined with contrast enhancement.

PMID- 23134821
TI  - Quantitative evaluation of extraocular muscle with high-field magnetic resonance
      in patients with Graves' ophthalmopathy with upper-lid retraction.
AB  - OBJECTIVE: To evaluate the feasibility of high-field magnetic resonance in
      measuring the thickness and width of extraocular muscles, calculate the ratio of
      thickness to width, and summarize the characters of the diameters and its ratio
      in patients with Graves' ophthalmopathy (GO) with upper-lid retraction. METHODS:
      Sixteen GO patients with upper-lid retraction (GO group) and 14 healthy control
      group were enrolled in this study. All the patients underwent enhanced high-field
      magnetic resonance orbital scan. The thickness and width of extraocular muscles
      were measured on axial, coronal or oblique sagittal enhanced T1 weighted images.
      The ratio of thickness to width (R1) and width to thickness (R2) were calculated.
      The diameters or ratio was evaluated as enlarged when they were 2 standard
      deviation greater than mean values of extraocular muscle in healthy control.
      RESULTS: The thickness of levator palpebrae superioris, medial rectus, and
      inferior rectus muscles in GO group were significantly larger than those in the
      control group (P=0.000, P=0.017, P=0.032, respectively. The width of superior
      oblique muscles in GO group was significantly larger than that in control group
      (P=0.000). The R1 values of levator palpebrae superioris, inferior rectus, medial
      rectus, and lateral rectus muscles in GO group were significant larger than those
      in the control group (P=0.000,P=0.037, P=0.019,P=0.032, respectively. The R2
      value of superior oblique muscles was significant larger than that in the control
      group (P=0.027). Aslo in GO group, 32 extraocular muscles showed an increased
      thickness. 47% of thickened extraocular muscles had an increased R1. CONCLUSIONS:
      Enhanced orbit imaging with high-field magnetic resonance is helpful in the
      quantitative assessment of the thickness and width of extraocular muscles. In GO
      patients, in addition to the levator palpebrae superioris muscles, some other
      extraocular muscles also becomes thicker. Moreover, the increased diameters of
      superior oblique muscles is mainly due to the increase of its width R1 and R2
      values can reflect the thickness and width of extraocular muscles and their
      relationship.

PMID- 23134822
TI  - Magnetic resonance imaging findings of pituitary hyperplasia due to primary
      hypothyroidism.
AB  - OBJECTIVE: To explore the clinical and magnetic resonance imaging (MRI) findings
      of pituitary hyperplasia due to primary hypothyroidism. METHOD: The clinical
      presentations, laboratory examinations, and MRI findings of 11 patients with
      pituitary hyperplasia secondary to primary hypothyroidism diagnosed at our
      hospitals from the beginning of 2008 to the end of 2011 were retrospectively
      reviewed. RESULTS: The clinical manifestations in 11 patients included growth
      arrest(7/8), mental retardation (6/8), cold intolerance and fatigue(6/11),
      slightly increased body weight (6/11), galactorrhea (3/11), paramenia (8/9),
      precocious puberty companying vaginal bleeding (2/2),and blurry vision (3/11).
      Laboratory investigations revealed grossly increased thyroid stimulating hormone,
      decreased thyroxine, and slightly elevated prolactin levels in all cases. Thyroid
      antibody was positive in six cases. On MRI, pituitary mass were detected a large
      intrasellar with/without suprasellar extension in all patients,showing the
      characteristic of symmetric enlargement. Spherical shape was viewed in 5
      cases,with the height of (12.22 +/- 3.12)mm. In the other 6 cases, the pituitary
      mass with the shape of calabash extended superiorly to suprasellar area, with a
      height of(18.95 +/- 2.23)mm. The signal of pituitary mass was isointense to grey
      matter both on T1 weighted imaging and T2 weighted imaging. Bright short T1
      signal in posterior lobe of pituitary was visible. Pituitary stalk was detected
      only in 4 cases from MRI without dislocation, while the width of pituitary stalk
      was within the normal limit. CONCLUSIONS: Pituitary hyperplasia should be
      considered when homogenous enlargement of the pituitary gland is found on MRI.
      The integration of MRI findings, clinical manifestations, and laboratory findings
      is helpful for the proper identification of the primary endocrine disease and
      thus avoid misdiagnosis.

PMID- 23134823
TI  - In vivo and in vitro imaging tracing of dual-labeled bone mesenchymal stem cells
      transplanted into myocardium of F344 rats.
AB  - OBJECTIVE: To investigate the feasibility of in vitro and in vivo magnetic
      resonance imaging (MRI) and fluorescence imaging tracking of transplanted bone
      mesenchymal stem cells (BMSCs) dual-labeled with ultrasmall superparamagnetic
      iron oxide (USPIO) and red fluorescence protein (RFP). METHODS: BMSCs were
      incubated with culture medium containing USPIO for 24 hours. The Prussian-blue
      staining, transmission electron microscopy and trypan-blue staining were used to
      study the efficacy and safety of labeling. F344 rat model of acute myocardial
      infarction was established by ligating the left anterior descending coronary
      artery. The dual-labeled BMSCs were injected into the margin of the infraction
      myocardium. Then MRI and fluorescence imaging were performed to trace the cells
      both in vitro and in vivo. Postmortal study was carried out to observe the
      distribution of transplanted cells in myocardium. RESULTS: The percentage of dual
      labeled BMSCs reached 99% after co-incubating with USPIO for 24 hours. USPIO
      particles were mainly located in lysosomes. As demonstrated by trypan-blue
      staining, there was no significant deference in viability between labeled and
      unlabeled groups (P>0.05). All dual-labeled transplanted BMSCs showed a
      significant decreasing signal on MRI, and the signal intensity changes had no
      significant difference over 4 weeks (P=0.66). In vitro cell tracing with
      fluorescence imaging of isolated heart from F344 rats was successful,while in
      vivo cell tracing with fluorescence imaging failed. Prussian blue staining showed
      that USPIO distributed near the infarcted myocardium, corresponding with the
      fluorescence imaging. CONCLUSION: MRI can be used to trace the dual-labeled BMSCs
      transplanted into F344 rat hearts in vivo, while fluorescence imaging and
      pathological fluorescence imaging can trace the transplanted cells in vitro.

PMID- 23134825
TI  - Diffusion weighted imaging and contrast-enhanced magnetic resonance imaging in
      the evaluation of early stage endometrial cancer.
AB  - OBJECTIVE: To assess the values of diffusion weighted imaging and contrast
      enhanced magnetic resonance imaging (MRI) in the evaluation of early endometrial
      cancer. METHODS: We retrospectively analyzed the imaging data of 27 patients with
      pathologically confirmed stage 1-2 endometrial cancer. These patients received
      pelvic magnetic resonance imaging, diffusion weighted imaging with apparent
      diffusion coefficient-T2 weighted imaging fusion images(ADC-T2WI), and T1
      weighted imaging (T1WI) of contrast-enhanced scan sequence. The accuracies of
      these image modes were analyzed and compared. RESULTS: The accuracy of routine
      pelvic MRI scan, diffusion weighted imaging with ADC-T2WI fusion images, and T1WI
      of contrast-enhanced scan for the early diagnosis of endometrial cancer was
      66.7%, 85.2%, and 92.5%, respectively. The sensitivity, specificity and
      diagnostic accuracy of diffusion weighted imaging with ADC-T2WI fusion images in
      the diagnosis of lesions with a 1/2 depth of muscle were 82.3%, 75%, and 85.2%.
      CONCLUSIONS: Routine pelvic MRI scan sequence has certain errors for the early
      diagnosis of endometrial cancer. On the contrary, the diffusion weighted imaging
      with ADC-T2WI image fusion has remarkably increased diagnostic accuracy. The T1WI
      of contrast-enhanced scan can clearly display most of the lesions by identifying
      the muscular infiltrations, and therefore can provide the most accurate
      information for the staging of early endometrial cancer.

PMID- 23134824
TI  - Comparison of computed tomography versus magnetic resonance imaging in assessing
      radiofrequency ablation margins after radiofrequency ablation in patients with
      hepatocellular carcinomas.
AB  - OBJECTIVE: To assess the diagnostic value of magnetic resonance imaging (MRI) in
      the follow-up of patients with hepatocellular carcinomas treated with
      radiofrequency ablation (RFA) and to compare it with that of computed tomography
      (CT). METHODS: From December 2009 to September 2011, 40 patients (47
      hepatocellular carcinomas) were treated with RFA after transcatheter arterial
      chemoembolization and underwent MRI and CT for follow-up. RFA margins were
      assessed on a five-point scale with receiver operating characteristic curve
      analysis. Sensitivity, specificity, positive predictive value, negative
      predictive value, and accuracy were evaluated. RESULTS: The interobserver
      agreement rate for MRI was significantly higher (Kappa=0.935) than for CT
      (Kappa=0.714; P < 0.05). The scores of 1 and 5 points for MRI, which confirms the
      presence or absence of residual tumor, accounted for 89.4% (84/94), while for CT
      accounting for only 31.9% (30/94). The area under the receiver operating
      characteristic curve of MRI was significantly higher than that of CT (P < 0.05),
      as were the sensitivity, specificity, positive predictive value, negative
      predictive value, and accuracy of detection rate (mean, 100%, 96.4%, 76.9%, 100%,
      and 96.8% for MRI, respectively, vs. 30.0%, 57.1%, 10.3%, 87.7%, and 63.8% for
      CT). CONCLUSION: MRI is superior to CT in assessing the RFA margins in terms of
      the diagnostic accuracy and detection rate .

PMID- 23134826
TI  - Role of magnetic resonance imaging in the diagnosis of lesions in the sellar
      region.
AB  - OBJECTIVE: To evaluate the role of magnetic resonance imaging (MRI) in the
      diagnosis of lesions in the sellar region. METHODS: The MRI data of 142 patients
      with surgically and pathologically proved lesions in the sellar region were
      retrospectively analyzed. Based on the MRI findings, the lesions were divided
      into pituitary adenoma and sellar region diseases except pituitary adenoma.
      According to the pathologic features, the sellar region diseases except pituitary
      adenoma were further divided into cystic lesions, parenchymatous lesions, and
      cystic and parenchymatous lesions. RESULTS: Of these 142 patients, pituitary
      adenoma was found in 30 cases, cystic lesions of sella region diseases except
      pituitary adenoma in 24. Further classification resulted in 66 cases of
      parenchymatous lesions and 22 cases of cystic and parenchymatous lesions.
      CONCLUSION: MRI-based classification of lesions in the sellar region is useful
      for the diagnosis and differential diagnosis.

PMID- 23134827
TI  - Role of diffusion weighted magnetic resonance imaging and spectroscopy in the
      diagnosis and follow-up of hepatolenticular degeneration.
AB  - OBJECTIVE: To explore the changes of different brain metabolites during
      hepatolenticular degeneration using diffusion weighted magnetic resonance imaging
      (DWI) and magnetic resonance spectroscopy (MRS) in patients with hepatolenticular
      degeneration and study the correlation of apparent diffusion coefficient(ADC)
      values and MRS with the different pathological changes. METHODS: Totally 53
      patients with hepatolenticular degeneration were enrolled in this study and
      divided into DWI high-signal group (n=31) and DWI low-signal group (n=22).
      Magnetic resonance scan, DWI, and spectroscopy were performed before treatment
      and 4 months after treatment. The changes of ADC value, N-acetyl aspartate
      (NAA)/creatine (Cr) ratio, and choline (Cho)/Cr ratio were recorded. RESULTS:
      Before treatment, the NAA/Cr ratio was significantly higher in the DWI high
      signal group than in DWI low-signal group (P=0.002), whereas ADC value and NAA/Cr
      ratio were significantly lower (P=0.004, P=0.014, respectively). After treatment,
      the NAA/Cr ratio was still significantly higher in the DWI high-signal group
      (P=0.036), while the differences of ADC value and Cho/Cr ratio showed no
      statistical deference (P>0.05). In the DWI high-signal group, the ADC value and
      NAA/Cr ratio were significantly elevated after treatment (P=0.006, P=0.008),
      whereas the Cho/Cr ratio showed no significant change (P>0.05). In the DWI low
      signal group, NAA/Cr ratio was significantly increased after treatment (P=0.015),
      while the ADC value and Cho/Cr ratio showed no significant change (P>0.05).
      CONCLUSIONS: DWI combined MRS imaging can be used to evaluate the microscopic
      structure and metabolic changes during copper deposition and thus, compared with
      the conventional magnetic resonance imaging provide more information on
      metabolism. Therefore, they can be useful tools in the early diagnosis and
      efficacy evaluation of hepatolenticular degeneration.

PMID- 23134828
TI  - Correlation of apparent diffusion coefficient with Ki-67 in the diagnosis of
      gliomas.
AB  - OBJECTIVE: To study the correlation between apparent diffusion coefficient (ADC)
      and Ki-67, a marker of tumor activity, in the diagnosis of gliomas. METHODS:
      Conventional magnetic resonance imaging (MRI), enhanced scanning, and diffusion
      weighted imaging were performed in 76 patients with pathologically confirmed
      gliomas. The ADC values were measured at tumor parenchyma and the corresponding
      contralateral normal brain. The relatively ADC (rADC) values of the tumor
      parenchyma were calculated. The correlation of the ADC values with tumor grades
      was analyzed. The expression of Ki-67 was detected by immunohistochemical
      staining. The correlation between ADC value and Ki-67 in the diagnosis of gliomas
      was analyzed. RESULTS: The ADC values and rADC values of high-grade gliomas were
      significantly lower than those of low-grade gliomas. The ADC values of tumor
      parenchyma were inversely associated with the degree of malignancy of the gliomas
      (r=-0.898, r=-0.868; P<0.01). The expression of Ki-67 was significantly higher in
      high-grade gliomas than that in low-grade gliomas. The Ki-67 labeling index in
      grade 3 and 4 gliomas were (29.48 +/- 19.78)% and (31.21 +/- 17.50)%,
      respectively. Both of them were significantly higher than Ki-67 labeling index in
      low-grade (grade 1 and 2) gliomas [(2.33 +/- 2.20)%] (P<0.01). Nevertheless, the
      Ki-67 labeling index showed no significant difference between grade 3 and 4
      gliomas (P>0.05). The expression of Ki-67 was negatively correlated with the ADC
      values and rADC values in tumor parenchyma (r=-0.627, r=-0.607; P<0.01).
      CONCLUSION: The ADC and rADC values of tumor parenchyma can indirectly reflect
      the proliferation and malignancy of gliomas and therefore can be useful for the
      grading of glioma.

PMID- 23134829
TI  - Genetic polymorphism of six transmembrane protein of prostate 2 associated with
      diabetes mellitus in Xinjiang Uygur population.
AB  - OBJECTIVE: To investigate the association between the genetic variations of six
      transmembrane protein of prostate 2 (STAMP2) with type 2 diabetes mellitus (T2DM)
      in Xinjiang Uygur population. METHODS: A case-control study was conducted based
      on epidemiological investigation. A total of 1838 Uygur subjects were selected
      and divided into two groups: T2DM group (n=274) and control group (n=1564). All
      exons, flanking introns, and the promoter regions of STAMP2 gene were sequenced
      in 48 Uygur Xinjiang population with diabetes. Representative variations selected
      were genotyped by TaqMan-PCR method in all individuals. RESULTS: Ten novel and 6
      known variations in the STAMP2 gene were identified. The distribution of genotype
      rs8122 significantly differed between T2DM group and control group (P=0.05),
      whereas the distribution of genotypes rs1981529 and rs34741656 showed no such
      difference. The fasting insulin in the total cohort and homeostasis model of
      assessment index in females showed significant difference between these two
      groups (P<0.05), while the adjusted P value showed no statistical significance
      (P>0.05). In the male population, the different genotypes of rs8122 variation of
      STAMP2 gene were not significantly different (P>0.05). CONCLUSION: Three
      polymorphisms (rs8122, rs1981529 and rs34741656) of STAMP2 gene may be not
      related with T2DM in Xinjiang Uygur population.

PMID- 23134830
TI  - Applied anatomy of a new approach of endoscopic technique in thyroid gland
      surgery.
AB  - OBJECTIVE: To explore the feasibility and safety of transtracheal assisted
      sublingual approach to totally endoscopic thyroidectomy by studying the
      anatomical approach and adjacent structures. METHODS: A total of 5 embalmed adult
      cadavers from Chengdu Medical College were dissected layer by layer in the
      cervical region, pharyngeal region, and mandible region, according to
      transtracheal assisted sublingual approach that was verified from the anatomical
      approach and planes. A total of 15 embalmed adult cadavers were dissected by
      arterial vascular casting technique, imaging scanning technique, and thin layer
      cryotomy. Then the vessel and anatomical structures of thyroid surgical region
      were analyzed qualitatively and quantitatively. Three-dimensional visualization
      of larynx artery was reconstructed by Autodesk 3ds Max 2010(32). Transtracheal
      assisted sublingual approach for totally endoscopic thyroidectomy was simulated
      on 5 embalmed adult cadavers. RESULTS: The sublingual observed access was located
      in the middle of sublingual region. The geniohyoid muscle, mylohyoid seam, and
      submental triangle were divided in turn in the middle to reach the plane under
      the plastima muscles. Superficial cervical fascia, anterior body of hyoid bone,
      and infrahyoid muscles were passed in sequence to reach thyroid gland surgical
      region. The transtracheal operational access was placed from the cavitas oris
      propria, isthmus faucium, subepiglottic region, laryngeal pharynx, and
      intermediate laryngeal cavit, and then passed from the top down in order to reach
      pars cervicalis tracheae where a sagittal incision was made in the anterior wall
      of cartilagines tracheales to reach a ascertained surgical region. CONCLUSION:
      Transtracheal assisted sublingual approach to totally endoscopic thyroidectomy is
      anatomically feasible and safe and can be useful in thyroid gland surgery.

PMID- 23134831
TI  - Effects of different liquid therapies on brain water content, intracranial
      pressure, and expressions of aquaporin-4 and N-methyl-D-aspartate receptor-1 in
      cerebral tissue.
AB  - OBJECTIVE: To explore the effects of different liquid therapies on the
      intracranial pressure, brain water content, and expressions of aquaporin-4 and N
      methyl-D-aspartate-1 in the brain tissue. METHODS: Two intervention factors
      including the colloids (two levels: 4% gelofusine; 6% hydroxyethyl starch and
      sodium chloride injection) and the crystal/gel ratios (two levels: 0:1; 1:1) were
      set based on the results of the analysis of variance of factorial design. Thirty
      two patient who had undergone epilepsy surgery were equally and randomly divided
      into four groups: group A (4% gelofusine, crystal/gel ratio 0:1); group B (6%
      hydroxyethyl starch and sodium chloride injection, crystal/gel ratio 0:1); group
      C (4% gelofusine, crystal/gel ratio 1:1); and group D (6% hydroxyethyl starch and
      sodium chloride injection, crystal/gel ratio 1:1). The intracranial pressure
      during operation was recorded. After the operation, the intracranial pressure and
      brain water content were measured and the expressions of aquaporin-4 and N-methyl
      D-aspartate-1 in the brain tissue were determined with Western blot. Glasgow coma
      scores were obtained 2 hours after operation. RESULTS: The intracranial pressure
      (F=55.714, P=0.000; F=142.432, P=0.000) and the brain water content (F=31.477,
      P=0.000; F=84.896, P=0.000) significantly increased after the application of the
      6% hydroxyethyl starch and sodium chloride injection and crystal/gel ratio 1:1,
      and the expressions of aquaporin-4 (F=37.205, P=0.000; F=149.652, P=0.014) and N
      methyl-D-aspartate-1(F=29.664, P=0.000; F=65.951, P=0.000) in the brain tissue
      significantly increased. There were additive effects between two of them (the
      intracranial pressure: F=11.056, P=0.002; the brain water content: F=8.007,
      P=0.008; the expression of aquaporin-4: F=9.845, P=0.004; and the expression of N
      methyl-D-aspartate-1: F=5.020, P=0.033). However, the Glasgow coma score showed
      no significant difference after the administration (P>0.05). CONCLUSION: The
      liquid therapy with 4% gelofusine and crystal/gel ratio 0:1 can result in better
      control on the intracranial pressure, brain water content and expressions of
      aquaporin-4 and N-methyl-D-aspartate-1 in the brain tissue better than the liquid
      therapy with 6% hydroxyethyl starch and crystal/gel ratio 1:1 during
      neurosurgery, although it may not improve the coma status.

PMID- 23134832
TI  - Value of diffusion weighted imaging in diagnosis and treatment of gastric cancer.
AB  - With the capability of measuring the water molecular diffusion qualitatively and
      quantitatively, diffusion weighted imaging (DWI) is currently the optimal and the
      only magnetic resonance method to observe water molecular diffusion motion in
      living tissues. Along with the advances in magnetic resonance technology,
      particularly the development of fast imaging sequences, DWI has been widely used
      in the imaging of liver, pancreas, kidneys and other solid organs. In recent
      years, DWI has been applied in the stomach. This article summarizes recent
      research on the application of DWI for the diagnosis and treatment of gastric
      cancer.

PMID- 23134833
TI  - Application of diffusion weighted imaging in rectal cancer diagnosis.
AB  - Magnetic resonance imaging has became the major method for rectal cancer
      diagnosis. As a novel magnetic resonance functional imaging technique, diffusion
      weighted imaging has improved the lesion detection sensitivity and provided more
      information on changes in body functions. The past two decades have witnessed the
      increasing application of this technique in clinical practices. This article
      summarizes the application of diffusion weighted imaging in rectal cancer
      diagnosis.

PMID- 23134834
TI  - Polymers containing phosphorus groups and polyethers: from synthesis to
      application.
AB  - BACKGROUND: Phosphorus-containing high performance polymers have aroused wide
      interest, mainly due to good mechanical properties and their excellent fire
      resistance. The flexibility of synthetic polyphosphoesters allows the development
      of polymers in order to obtain solid polymer electrolytes for rechargeable
      lithium batteries based on solid films with superior fire resistance. RESULTS:
      Novel linear Phosphonate-PEG polymers were synthesized by solution
      polycondensation of 4-chlorophenyldichlorophosphonate as a linking agent and
      poly(ethylene glycol)s with different molecular weights in the presence of
      triethylamine or 1-methylimidazole as acid scavenger. The yields were between 54%
      and 88% and inherent viscosity between 0.18-0.48 dl/g. Molar masses, Mn were
      about 26300 g/mol for polyphosphonates with PEG 2000 and 4600 g/mol for
      polyphosphonates with PEG 200. The LOI values for these polymers and membranes
      are in the range of 26-29. The membranes based on polyphosphonate with PEG 200
      and 2000 showed conductivity between 6 * 10-8 S.cm-1 and 6 * 10-7 S.cm-1 at room
      temperature and total ionic transference number between 0.87- 0.96. The evolution
      of conductivity vs. temperature is linear. CONCLUSIONS: 1-methylimidazole was
      found to be better HCl scavenger than triethylamine, and allowed higher yields
      and more eco-friendly synthesis of the Phosphonate-PEG polymers for SPE. These
      polymers and membranes based on these polymers showed good LOI values and
      indicate an improvement of the safety of lithium batteries. The membranes present
      conductivities around 6 * 10-7 S.cm-1at room temperature and total ionic
      transference number is higher for membranes based on polymers with high EG unit
      content. Best results yield 88%, inherent viscosities 0.48 dl/g and Mn 26000 were
      obtained with 1-methylimidazole and PEG 2000. These membranes based on these
      polymers showed good LOI values (in the range 26-29%) and indicate an improvement
      of the safety of lithium batteries.

PMID- 23134835
TI  - Drug law reform: when bad policy is good politics.

PMID- 23134836
TI  - Prevention of CAUTI: simple is beautiful.

PMID- 23134837
TI  - Antimicrobial catheters for reduction of symptomatic urinary tract infection in
      adults requiring short-term catheterisation in hospital: a multicentre randomised
      controlled trial.
AB  - BACKGROUND: Catheter-associated urinary tract infection (CAUTI) is a major
      preventable cause of harm for patients in hospital. We aimed to establish whether
      short-term routine use of antimicrobial catheters reduced risk of CAUTI compared
      with standard polytetrafluoroethylene (PTFE) catheterisation. METHODS: In our
      parallel, three group, multicentre, randomised controlled superiority trial, we
      enrolled adults (aged >=16 years) requiring short-term (<=14 days)
      catheterisation at 24 hospitals in the UK. Participants were randomly allocated
      1:1:1 with a remote computer allocation to receive a silver alloy-coated
      catheter, a nitrofural-impregnated catheter, or a PTFE-coated catheter (control
      group). Patients undergoing unplanned catheterisation were also included and
      consent for participation was obtained retrospectively. Participants and trial
      staff were unmasked to treatment assignment. Data were collected by trial staff
      and by patient-reported questionnaires for 6 weeks after randomisation. The
      primary outcome was incidence of symptomatic urinary tract infection for which an
      antibiotic was prescribed by 6 weeks. We postulated that a 3.3% absolute
      reduction in CAUTI would represent sufficient benefit to recommend routine use of
      antimicrobial catheters. This study is registered, number ISRCTN75198618.
      FINDINGS: 708 (10%) of 7102 randomly allocated participants were not
      catheterised, did not confirm consent, or withdrew, and were not included in the
      primary analyses. Compared with 271 (12.6%) of 2144 participants in the control
      group, 263 (12.5%) of 2097 participants allocated a silver alloy catheter had the
      primary outcome (difference -0.1% [95% CI -2.4 to 2.2]), as did 228 (10.6%) of
      2153 participants allocated a nitrofural catheter (-2.1% [-4.2 to 0.1]). Rates of
      catheter-related discomfort were higher in the nitrofural group than they were in
      the other groups. INTERPRETATION: Silver alloy-coated catheters were not
      effective for reduction of incidence of symptomatic CAUTI. The reduction we noted
      in CAUTI associated with nitrofural-impregnated catheters was less than that
      regarded as clinically important. Routine use of antimicrobial-impregnated
      catheters is not supported by this trial. FUNDING: UK National Institute for
      Health Research Health Technology Assessment Programme.

PMID- 23134838
TI  - Acetate supplementation reduces microglia activation and brain interleukin-1beta
      levels in a rat model of Lyme neuroborreliosis.
AB  - BACKGROUND: We have found that acetate supplementation significantly reduces
      neuroglia activation and pro-inflammatory cytokine release in a rat model of
      neuroinflammation induced with lipopolysaccharide. To test if the anti
      inflammatory effect of acetate supplementation is specific to a TLR4-mediated
      injury, we measured markers of neuroglia activation in rats subjected to B.
      burgdorferi-induced neuroborreliosis that is mediated in large part by a TLR2
      type mechanism. METHODS: In this study, rats were subjected to Lyme
      neuroborreliosis following an intravenous infusion of B. burgdorferi (B31-MI-16).
      Acetate supplementation was induced using glyceryl triacetate (6g/kg) by oral
      gavage. Immunohistochemistry, qPCR, and western blot analyses were used to
      measure bacterial invasion into the brain, neuroglial activation, and brain and
      circulating levels of interleukin 1beta. Statistical analysis was performed using
      one-way analysis of variance (ANOVA) followed by a Tukey's post hoc tests or
      using a Student's t test assuming unequal variances when appropriate. RESULTS: We
      found that acetate supplementation significantly reduced microglia activation by
      2-fold as determined by immunohistochemical and western blot analysis. Further,
      acetate supplementation also reduced the expression of the pro-inflammatory
      cytokine IL-1beta by 2-fold as compared to controls. On the other hand, the
      inoculation of rats with B. burgdorferi had no effect on astroglial activation as
      determined by immunocytochemistry and western blot analysis despite significant
      increases in circulation levels of antigen toward B. burgdorferi and presence of
      the bacteria in the central nervous system. CONCLUSIONS: These results suggest
      that microglial activation is an essential component to neuroborreliosis and that
      acetate supplementation may be an effective treatment to reduce injury phenotype
      and possibly injury progression in Lyme neuroborreliosis.

PMID- 23134839
TI  - Arm trajectories and writing strategy in healthy children.
AB  - BACKGROUND: Evaluation of elementary writing skills in children is usually
      obtained with high resolution (and high cost) techniques or with low resolution
      pen-and-paper tests. In this observational study we tested a quantitative method
      to obtain normative data to describe arm movement during a writing precursor
      gesture. METHODS: We recruited 226 healthy children (mean age 9,1 years [range:
      6.3 - 11.4 years]), attending primary schools belonging to the "Istituto
      Comprensivo" of Rivanazzano Terme (Pavia). We asked to drive a cursor through a
      polygonal path (labyrinth) projected in front of them using a wireless mouse.
      DartfishTM video analysis software was used to elaborate images and ExcelTM,
      MedCalcTM and Statistica 7TM to analyze values of shoulder, elbow and wrist
      ranges of motion, arm trajectories, execution times and gesture accuracy.
      RESULTS: Differences seen in motor strategies, when divided according to attended
      class, suggest a proximal-distal maturation of motor control. Obtained values
      were not significantly correlated with variables such as gender, ethnicity or
      cognitive functioning. CONCLUSIONS: This type of approach to a study of arm
      movement during childhood represents a valid alternative to other tests,
      considering that it can differentiate children who perform similarly in the VMI
      test and is non-invasive, low-cost and easily reproducible.

PMID- 23134840
TI  - Thyroid lymphoma: diagnostic pitfalls on pre-operative ago-biopsy.
AB  - BACKGROUND: Thyroid cancer has the highest prevalence of all endocrine
      malignancies. Malignancy can be of thyroid or non-thyroid origin. Sarcomas and
      primary thyroid lymphomas (PTL) are rare and surgery is treatment of choice in
      the former but not in latter. OBJECTIVE: To describe thyroid lymphomas
      histological types of thyroid cancer found in a reference center. METHODS:
      Medical chart review from admitted patients diagnosed with thyroid cancer in the
      period from january 2007 to june 2012. Demographic, diagnostic, therapeutic and
      histopathological information were collected. RESULTS: 1604 records of patients
      admitted with thyroid disease were reviewed. Among 307 thyroid cancer, the cases
      diagnosed with rare tumors were: 10 cases of anaplastic carcinoma (3.5%),
      followed by 4 cases of medullary carcinoma (1.3%), 1 cases of teratoma (0.03%), 2
      cases of lymphoma (0.06%). The most frequent clinical presentation was a palpable
      thyroid nodule. All patients with lymphoma died. CONCLUSION: Thyroid lymphomas
      are uncommon and tend to worse outcomes.

PMID- 23134841
TI  - Prevalence of muscle-strengthening activities in women: the WIN study.
AB  - BACKGROUND: Aerobic and muscle-strengthening activities are related to
      morbidities and mortality. Resistance exercise/strength training items are
      included in national surveys, but the manner in which muscle-strengthening
      activity is queried varies among these surveys. PURPOSE: The purpose of this
      study was to use different self-report measures to examine the prevalence of
      meeting the 2008 Physical Activity Guidelines for Americans regarding muscle
      strengthening activities among women. METHODS: We surveyed 606 community-dwelling
      women at 4 points in time across a 1.5- to 3-year time period to determine
      whether the respondents met the national physical activity guidelines for
      performing muscle-strengthening activities >= 2 days per week. RESULTS: Results
      were consistent across time but depended on the manner in which the question was
      asked. If asked to reflect over the past month or a general question about the
      typical number of days engaged, approximately 40% of women reported engaging in
      >= 2 days per week of resistance exercise/strength training. However, when
      reports were obtained weekly for 13 weeks, only approximately 18% of respondents
      met the guidelines. CONCLUSION: Results indicate that the timing and nature of
      questioning can substantially influence the self-reported prevalence of muscle
      strengthening physical activities for community-dwelling women.

PMID- 23134842
TI  - Characterization of replication and conjugation of plasmid pWTY27 from a widely
      distributed Streptomyces species.
AB  - BACKGROUND: Streptomyces species are widely distributed in natural habitats, such
      as soils, lakes, plants and some extreme environments. Replication loci of
      several Streptomyces theta-type plasmids have been reported, but are not
      characterized in details. Conjugation loci of some Streptomyces rolling-circle
      type plasmids are identified and mechanism of conjugal transferring are
      described. RESULTS: We report the detection of a widely distributed Streptomyces
      strain Y27 and its indigenous plasmid pWTY27 from fourteen plants and four soil
      samples cross China by both culturing and nonculturing methods. The complete
      nucleotide sequence of pWTY27 consisted of 14,288 bp. A basic locus for plasmid
      replication comprised repAB genes and an adjacent iteron sequence, to a long
      inverted-repeat (ca. 105 bp) of which the RepA protein bound specifically in
      vitro, suggesting that RepA may recognize a second structure (e.g. a long stem
      loop) of the iteron DNA. A plasmid containing the locus propagated in linear mode
      when the telomeres of a linear plasmid were attached, indicating a bi-directional
      replication mode for pWTY27. As for rolling-circle plasmids, a single traA gene
      and a clt sequence (covering 16 bp within traA and its adjacent 159 bp) on pWTY27
      were required for plasmid transfer. TraA recognized and bound specifically to the
      two regions of the clt sequence, one containing all the four DC1 of 7 bp
      (TGACACC) and one DC2 (CCCGCCC) and most of IC1, and another covering two DC2 and
      part of IC1, suggesting formation of a high-ordered DNA-protein complex.
      CONCLUSIONS: This work (i) isolates a widespread Streptomyces strain Y27 and
      sequences its indigenous theta-type plasmid pWTY27; (ii) identifies the
      replication and conjugation loci of pWTY27 and; (iii) characterizes the binding
      sequences of the RepA and TraA proteins.

PMID- 23134843
TI  - Specific PABP effect on translation of YB-1 mRNA is neutralized by
      polyadenylation through a "mini-loop" at 3' UTR.
AB  - YB-1 is a multifunctional cold shock domain containing protein that is involved
      virtually in all DNA- and mRNA-dependent cellular events. Its amount is regulated
      at the level of both transcription and translation. We showed previously that
      translation of poly A(-) YB-1 mRNA in vitro is selectively controlled by two
      proteins, YB-1 and PABP, through their specific and competitive binding to a
      regulatory element (RE) within 3' UTR of this mRNA. Here, we describe effects of
      these two proteins on translation of poly A(+) as compared with poly A(-) YB-1
      mRNA in a rabbit reticulocyte cell-free translation system. We have found that YB
      1 inhibits translation of both poly A(+) and poly A(-) YB-1 mRNAs at the same
      comparatively low YB-1/mRNA ratio. PABP has no positive effect on translation of
      poly A(+) YB-1 mRNA, although it has a stimulating effect on translation of poly
      A(-) YB-1 mRNA. A positive PABP effect on translation of poly A(+) YB-1 mRNA
      arose after removal of a portion of the sequence between RE and the poly(A) tail
      and disappeared after its replacement by another non-specific sequence of the
      same length. We also report that the RE fragment forms a complex with the poly(A)
      fragment in the presence of rabbit reticulocyte lysate (RRL) proteins. For its
      formation PABP is necessary but not sufficient. These results are in agreement
      with the proposed model implying formation of a mini-loop at 3' UTR of YB-1 mRNA
      that includes RE, RRL proteins and the poly(A) tail.

PMID- 23134844
TI  - Low dielectric polyimide aerogels as substrates for lightweight patch antennas.
AB  - The dielectric properties and loss tangents of low-density polyimide aerogels
      have been characterized at various frequencies. Relative dielectric constants as
      low as 1.16 were measured for polyimide aerogels made from 2,2'-dimethylbenzidine
      (DMBZ) and biphenyl 3,3',4,4'-tetracarbozylic dianhydride (BPDA) cross-linked
      with 1,3,5-triaminophenoxybenzene (TAB). This formulation was used as the
      substrate to fabricate and test prototype microstrip patch antennas and benchmark
      against state of practice commercial antenna substrates. The polyimide aerogel
      antennas exhibited broader bandwidth, higher gain, and lower mass than the
      antennas made using commercial substrates. These are very encouraging results,
      which support the potential advantages of the polyimide aerogel-based antennas
      for aerospace applications.

PMID- 23134845
TI  - Toward a typology of health-related informal credit: an exploration of borrowing
      practices for paying for health care by the poor in Cambodia.
AB  - BACKGROUND: Borrowing money is a common strategy to cope with health care costs.
      The impact of borrowing on households can be severe, leading to indebtedness and
      further impoverishment. However, the available literature on borrowing practices
      for health is limited. We explore borrowing practices for paying for health care
      by the poor in Cambodia and provide a typology, associated conditions, and the
      extent of the phenomenon. METHODS: In addition to a semi-structured literature
      review, in-depth interviews were conducted with representatives of 47 households
      with health-related debt and 19 managers of formal or informal credit schemes.
      RESULTS: A large proportion of Cambodians, especially the poor, resort to
      borrowing to meet the cost of health care. Because of limited cash flow and
      access to formal creditors, the majority take out loans with high interest rates
      from informal money lenders. The most common type of informal credit is locally
      known as Changkar and consists of five kinds of loans: short-term loans, medium
      term loans, seasonal loans, loans for an unspecified period, and loans with
      repayment in labour, each with different lending and repayment conditions and
      interest rates. CONCLUSION: This study suggests the importance of informal credit
      for coping with the cost of treatment and its potentially negative impact on the
      livelihood of Cambodian people. We provide directions for further studies on
      financial protection interventions to mitigate harmful borrowing practices to pay
      for health care in Cambodia.

PMID- 23134846
TI  - Cognitive enhancers are set to change workplaces.

PMID- 23134847
TI  - [Building of hematopoietic stem cell transplantation system with Chinese
      characteristics].

PMID- 23134848
TI  - [Going a long way to improve the anti-infection level in hematologists].

PMID- 23134849
TI  - [Testicular swelling as the first manifestation of IgD- multiple myeloma: a case
      report].

PMID- 23134850
TI  - [Cytomegalovirus-specific T cells immune reconstitution after human leukocyte
      antigen matched sibling donor allogeneic bone marrow plus peripheral blood
      hematopoietic stem cell transplantation].
AB  - OBJECTIVE: To investigate the regular pattern of Cytomegalovirus (CMV)-specific T
      cells (CTL) immune reconstitution after human leukocyte antigen (HLA) matched
      sibling donor allogeneic bone marrow(BM) plus peripheral blood hematopoietic stem
      cell (PBSC) transplantation. METHODS: CTL from seventeen patients after
      transplantation was detected by flow cytometry, the IFN-gamma secretion ability
      of CTL by enzyme-linked immunospot (ELISPOT) assay, and clonal analysis of TCR
      Vbeta subfamily by gene scan assays. The relationship between CTL reconstitution
      and CMV infection was studied. RESULTS: Both number and function of recipients
      CTL reached to normal control level at 30 d post-transplantation. The recipients
      achieved a high frequency CTL with IFN-gamma response and restoration of T-cell
      receptor beta (TCR Vbeta) repertoire at one year post-transplantation. CTL with
      the central memory CD45RO(+)CD62L(+) cell phenotype expanded in PB when CMV was
      reactivated. The incidence of CMV reactivation was 35.83% (17.91% - 63.10%) after
      transplantation, and none of them developed CMV disease. CONCLUSION: After HLA
      matched related donor transplantation using mixed grafts, immune recovery to CMV
      seems to be early and fast. The incidence of CMV infection and disease are low.

PMID- 23134851
TI  - [Outcome of allogeneic hematopoietic stem cell transplantation from HLA-matched
      sibling donor for 41 cases of severe aplastic anemia].
AB  - OBJECTIVE: To evaluate the outcome of allogeneic hematopoietic stem cell
      transplantation (allo-HSCT) from HLA-matched sibling donor (MSD allo-HSCT) for
      severe aplastic anemia (SAA). METHODS: The clinical data of 41 SAA patients
      received MSD allo-HSCT from May. 2003 to Aug. 2011 were analyzed retrospectively.
      24 patients were male, 17 were female. Median age was 23 (5 - 43) years old. 28
      patients had SAA-I, 9 had SAA-II, and 4 had post-hepatitis aplastic anemia. 17
      patients received allogeneic bone marrow (BM) transplantation (allo-BMT), and 24
      received allogeneic peripheral blood stem cell (PBSC) transplantation (allo
      PBSCT). The conditioning regimens: 20 patients received cyclophosphamide (CY) +
      anti-thymocyte globulin (ATG) + fludarabine (Flu), 21 received CY + ATG + Flu+
      cytarabine (Ara-C) +/- busulfan (Bu)/melphalan (Mel). Prophylaxis for graft
      versus-host disease (GVHD): 25 patients received cyclosporine (CSA) plus short
      term methotrexate (MTX), 16 received tacrolimus (FK506) plus short-term MTX. The
      median number of infused CD34(+) cells were 3.48 (2.39 - 4.80)*10(6)/kg in allo
      BMT and 2.95 (1.27 - 5.98)*10(6)/kg in allo-PBSCT, respectively. RESULTS:
      Hematopoietic reconstitution was observed in all 41 patients (100%). The median
      time of neutrophils (ANC) reached to 0.5*10(9)/L and platelets (PLT) reached to
      20*10(9)/L were 14 (10 - 23) days and 19 (8 - 38) days, respectively. 12 patients
      developed acute GVHD (aGVHD), out of which 11 developed grade I-II aGVHD, and one
      developed grade IV. 2 patients occurred chronic GVHD (cGVHD), out of which one
      with local cGVHD and the other with extensive. 4 patients occurred graft
      rejection (GR), all of them recovered haemopoiesis and survived after donor PBSC
      infusion. 5 patients (12.2%) died, out of which one died of extensive cGVHD, and
      4 died of invasive fungal infections (IFI). Median follow-up time was 23 (3 - 79)
      months. 36 patients survived. 5-year estimated overall survival (OS), disease
      free survival (DFS), and transplant-related mortality (TRM) was (81.1 +/- 9.0)%,
      (68.4 +/- 11.0)%, and (18.9 +/- 9.0)%, respectively. Univariate analysis showed
      that lover OS had significant correlation with receiving PBSCT, occurrence of
      aGVHD, the number of infused CD34(+) cells no more than 2.5*10(6)/kg, the number
      of red blood cell (RBC) transfusion before transplant more than 30 U and
      occurrence of IFI after transplantation (P = 0.034, 0.001, 0.006, 0.000, 0.001,
      respectively). Occurrence of aGVHD had significant correlation with the disparity
      between donor and recipient ABO blood groups, the number of PLT transfusion more
      than 100 U, and the number of RBC transfusion more than 30 U before
      transplantation, the number of infused CD34(+) cells no more than 2.5* 10(6)/kg
      (P = 0.019, 0.038, 0.005, 0.005, respectively). The occurrence of GR had
      significant correlation with the number of PLT transfusion more than 100 U before
      transplantation (P = 0.038). CONCLUSION: MSD allo-HSCT is an effective therapy
      for patients with SAA. Lower number of blood transfusion before transplantation,
      use of BMT, more number of infused CD34(+) cells can effectively prevent and
      treat aGVHD and IFI after transplantation, which may improve the efficacy of MSD
      allo-HSCT for SAA.

PMID- 23134852
TI  - [Study on chronic health conditions and its related risk factors in recipients
      after hematopoietic stem cell transplantation].
AB  - OBJECTIVE: To study the chronic health conditions (CHC) in long-term survival
      recipient after hematopoietic stem cell transplantation (HSCT). METHODS: The CHC
      of 101 cases survived for more than 1 year after HSCT were collected according to
      Bone Marrow Transplant Survivor Study (MBMTSS) questionnaire. The differences of
      the incidence and severity of CHC between auto-HSCT and allo-HSCT, HLA-matched
      and HLA-mismatched family donors HSCT were compared, and risk factors related to
      chronic health conditions were analyzed retrospectively in family donor HSCT.
      RESULTS: Of the 101 HSCT survivors, 48.5% reported one or more chronic health
      conditions, and 83.7% of which were mild to moderate. The CHC in HLA-matched
      related donors HSCT were more serious than in HLA-mismatched related donors HSCT.
      The percentage of CHC total score above 3 in allo-HSCT recipients (32.1%) was
      higher than that in auto-HSCT ones (10.0%). The percentage of CHC total score 1
      2, 3-4, and above 5 in HLA-matched family donors HSCT were 23.5%, 29.4%, and
      14.7%, respectively, being significantly higher than those in HLA-mismatched ones
      (15.6%, 15.6%, and 6.2%, respectively). CHC was mainly related to chronic graft
      versus-host disease (cGVHD). Single variable analysis showed that younger age at
      time of transplantation, HLA fully matched, the use of antithymocyte globulin
      (ATG) in the conditioning regimens were favorable for CHC. COX-regression Model
      showed that age was the only independent risk factor for predicting the CHC in
      family donor HSCT. CONCLUSION: The chronic health conditions after HSCT is mild
      to moderate, these complications in HLA-matched related donor HSCT are more
      serious than those in HLA-mismatched related donor HSCT. The age at
      transplantation is the only independent risk factor for chronic health
      conditions.

PMID- 23134853
TI  - [Additional karyotypic abnormalities analysis in patients with hematological
      malignancies post-allogeneic hematopoietic stem cell transplantation].
AB  - OBJECTIVE: To analyze the karyotype stability in hematological malignancies
      patients before and after allogeneic hematopoietic stem cell transplantation
      (allo-HSCT) and its prognostic significance of monitoring. METHODS: The
      karyotypes and clinical data of 21 patients with hematological malignancies at
      the initial diagnosis and at relapse after allo-HSCT were retrospectively
      reviewed. Chromosome analysis was performed by standard 24 h-cultured method and
      R banding. RESULTS: Karyotypes at the initial diagnosis and at relapse after allo
      HSCT were different in 11 patients (52.38%), including chromosome 1, 3, 6, 12,
      17, 21. Numberical abnormalities and structural chromosomal abnormalities always
      occurs together. The median survival time of relapse of the patients with
      karyotype changes was significantly shorter than that of patients without a
      karyotype change (79 d vs 522 d, P = 0.027), and that of the patients with
      trisomy 6 was also significantly shorter than that of the patients without
      trisomy 6 (9 d vs 275 d, P = 0.005). CONCLUSION: Karyotype changes after relapse
      are associated with the prognosis of allo-HSCT.

PMID- 23134854
TI  - [Recovery of vascular niche in bone marrow by donor derived endothelial
      progenitor cells after allogeneic bone marrow transplantation in mice].
AB  - OBJECTIVE: To investigate the role of endothelial progenitor cell (EPC) injection
      in the restoration of vascular niche in bone marrow (BM) after allo-BMT in mice,
      and to observe its role on hematopoietic reconstitution. METHODS: 6-8 weeks old
      female BALB/c (H-2(d)) were randomized to BMT (allo-BMT) group and combined EPC
      transplant (allo-BMT + EPC) group. For allo-BMT group, female BALB/c mice were
      lethally irradiated with 60Co source, and then were injected intravenously with
      5*10(6) BM cells from donor mice. In allo-BMT + EPC group, recipient mice were
      injected intravenously with 5*10(6) BM cells and 5*10(5) EPC from donor mice. The
      recipients were monitored for histological changes of endothelial cells (EC) in
      BM. The recovery of hematopoiesis was determined by white blood cell counts and
      the proportion of reticulocytes in circulation and the proportion of
      hematopoietic stem cells (HSC) in BM. The histology of hematopoiesis in BM was
      also detected. RESULTS: The in vitro induced EPC successfully homed to the bone
      marrow of recipients. The ECs of allo-BMT recipients were destructed severely,
      while the structures of ECs were restored in EPC treated recipients. 10 and 15
      days after allo-BMT, the amount of Lin-c-kit(+)Sca-1(+) cells in the BM of the
      EPC treated group were (20.31 +/- 2.65)*10(3) per mouse and (10.26 +/-
      2.19)*10(3) per mouse, while the allo-BMT group's were (9.61 +/- 0.98)*10(3) per
      mouse and (4.09 +/- 1.34)*10(3) per mouse; and 15 days after allo-BMT, the amount
      of white blood cell counts and proportion of reticulocytes of the EPC treated
      group were (1.20 +/- 0.11)*10(9)/L and (2.35 +/- 0.30)% comparing to the allo-BMT
      group which were (0.65 +/- 0.10)*10(9)/L and (1.63 +/- 0.20)%. CONCLUSION: Co
      transfer of donor EPC restores the ECs of bone marrow, which consequently
      promotes hematopoietic reconstitution in murine allo-BMT.

PMID- 23134855
TI  - [The primary diffuse large B-cell lymphoma of the urinary bladder: a case
      report].

PMID- 23134856
TI  - [Clinical study on high-dose etoposide with granulocyte colony-stimulating factor
      for mobilization of autologous peripheral blood stem cells in patients with
      hematologic malignancies].
AB  - OBJECTIVE: To explore the effectivity and safety of single high-dose (HD)
      etoposide (Vp16) with granulocyte colony-stimulating factor (G-CSF) for
      mobilization of autologous peripheral blood stem cells (PBSC) in patients with
      hematologic malignancies. METHODS: 80 patients of hematologic malignancies
      including 20 patients with acute leukemia (AL), 23 with multiple myeloma (MM), 35
      with non-Hodgkin's lymphoma (NHL) and 2 with Hodgkin's lymphoma (HL) received
      Vp16 (1.6 g/m(2)) continuous intravenous infusion for 10 hrs on day 1. G-CSF at
      10 ug/kg once daily subcutaneous injection began to use on day of ANC lower than
      1*10(9)/L and continued until PBSC collection was completed. Autologous PBSC
      (APBSC) was collected on day of WBC greater than 5*10(9)/L and continuing until
      the collection goal was met (target value: MNC >= 6.0*10(8)/kg and CD34(+) >=
      2.0*10(6)/kg). The patients received APBSC after conditioning regimen. The number
      of the cells collection, time of hematopoietic reconstruction, adverse effect and
      so on were observed during the course of stem cell mobilization and collection.
      RESULTS: PBSC was collected on day 11 (range: 7 - 25 days) of after Vp16
      administration with a median collection time of 2 (range 1 - 5). 3/80 patients
      with AML got stem cell mobilization failure. 5 of 6 patients who failed to
      mobilize before got successful stem cell mobilization, 1/6 patient with AML-M(5)
      got a second failure after the mobilization of VP16 whose first time's
      mobilization using Ara-C did not succeed. The median number of CD34(+) cells
      collected in 77 patients who got successful mobilization was 4*10(6)/kg ?[range
      (1.59 - 24.68)*10(6)/kg?]. The collection of 20 patients with AL and 23 with MM
      were got detection for minimal residual disease, no pollution of tumor cells were
      happened. All patients could tolerate the whole course of stem cell mobilization.
      29/80 (36.25%) patients got a 4 grade leucopenia, 19/80 (23.75%) patients got
      infection. CONCLUSION: Single high-dose etoposide with G-CSF for mobilization of
      APBSC has a higher achievement ratio, a controllable adverse effect, a promising
      hematopoiesis recovery, which is an effective and safe mobilizing regimen for
      patients with hematologic malignancies.

PMID- 23134858
TI  - [Acute liver failure as the first manifestation of IgM multiple myeloma: a case
      report].

PMID- 23134857
TI  - [The correlation between early lymphocyte count post-allogeneic hematopoietic
      stem cell transplantation and prognosis in leukemia patients].
AB  - OBJECTIVE: To analyze the correlation between early lymphocyte count (lymphocyte
      count on day 30, LC30) post-allogeneic hematopoietic stem cell transplantation
      (allo-HSCT) and transplant prognosis in leukemia patients. METHODS: The data from
      124 consecutive patients undergoing allo-HSCT for leukemia from January 2003 to
      April 2011 was analyzed retrospectively. LC30 post-allo-HSCT correlated with 5
      year overall survival (OS), 5-year relapse rate (RR), 5-year nonrelapse mortality
      (NRM), accumulative rate of acute graft versus host disease (aGVHD) and chronic
      graft versus host disease (cGVHD) was studied. RESULTS: Univariate analysis
      indicated that patients with LC30 >= 0.40*10(9)/L had higher 5-year OS than those
      with LC30 < 0.40*10(9)/L ?[(62.2 +/- 5.8)% vs (37.0 +/- 8.6)%, P = 0.003?], lower
      5-year RR?[(13.9 +/- 4.7)% vs (32.0 +/- 8.4)%, P = 0.027?], lower 5-year NRM
      ?[(31.3 +/- 5.8)% vs (45.0 +/- 9.3)%, P = 0.048)?], and higher cGVHD cumulative
      incidence ?[(82.9 +/- 4.6)% vs (62.7 +/- 11.1)%, P = 0.042)?]. Multivariate
      analysis also suggested that LC30 was associated with 5-year OS, 5-year RR, 5
      year NRM, and cGVHD cumulative incidence. At the same time disease risk
      stratification was associated with prognosis. CONCLUSIONS: Early lymphocyte count
      (LC30) post-allogeneic hematopoietic stem cell transplantation in leukemia is
      highly associated with prognosis, which can be the independent prognosis index
      after allo-HSCT in leukemia and can identify a group of patients who might be
      suitable candidates for early interventions treatment.

PMID- 23134859
TI  - [Study on serological blood group conversion rule and clinical blood transfusion
      in allogeneic hematopoietic stem cell transplantation].
AB  - OBJECTIVE: To explore the conversion rule of serological blood group and blood
      group substance after successful allogeneic hematopoietic stem cell
      transplantation, and to provide theory for clinical special blood type
      identification and blood transfusion. METHODS: The growth cycle of recipient WBC
      and RBC, RBC chimera, blood group antibody production and remaining in full
      transition were observed. Conversion rule of blood group substance, contradiction
      between cells typing and sera typing were detected by saline medium tube method
      and microcolumn gel method after stem cells transplantation. RESULTS: The average
      time of engraftment in 21 recipients was about 18.6 days, RBC growth cycle in 8
      major blood type incompatibility was 56.6 days, 25.9 days in 9 minor blood type
      incompatibility, 67 days in 4 bidirectional blood type incompatibility (P <
      0.01). The ratio of RBC chimeric growth was 1:9, gradually converse to donor's
      blood group. Residue of recipient anti-A(B) was left after conditioning regimen,
      disappeared after full transformation, and recipient anti-A(B) was converse to
      donor's blood type in major blood type incompatibility. 5 A blood type recipient
      donated by O blood type blood generated anti-B instead of anti-A, 3 B blood type
      recipient generated only anti-A instead of B in minor blood type incompatibility,
      and 1 AB blood type recipient donated by A did not generate anti-B. Among 4
      bidirectional blood type incompatibility, 2 B blood type recipient donated by A
      blood type blood did not generate anti-B, 2 A recipient by B could not produce
      anti-A. Recipient blood group substance helped original ABO blood type substance
      remain unchanged. CONCLUSION: Among patient with allogeneic hematopoietic stem
      cell transplantation, recipient's ABO and RBC blood type can be converse to
      donor's, but there is significant difference between patients of serological
      blood group and of normal people (P < 0.01). Recipient blood group substance
      helps original ABO blood type substance remain unchanged (P > 0.01).

PMID- 23134860
TI  - [The molecular mechanism of haemophilia B caused by the Arg327Ile novel mutation
      in FIX gene in vitro expression].
AB  - OBJECTIVE: To investigate the molecular mechanism of haemophilia B caused by the
      novel mutation of Arg327Ile (R327I) in FIX gene. METHODS: The R327I, R327Ala(A),
      R327Lys(K), R327Asn(N) and a replacement mutant (FIXbetaFVII), in which FIX beta
      strand 324-329 was replaced by that of FVII 298-303, expression plasmids were
      constructed with site-directed mutagenesis method based on the wild-type (WT) FIX
      expression plasmid. The HEK293 cell was transiently transfected, then the
      activity of FIX (FIX:C) was assayed by one stage method in the conditioned
      medium, while the FIX:Ag in both the conditioned media and the cell lysates was
      measured by ELISA. The molecular weight and the semi-quantity of expressed FIX
      were analyzed by Western blot. Fluorescent protein expression plasmid was
      constructed to investigate the synthesis and secretion of the FIX R327I mutation
      in the viable cells. RESULTS: FIX:C of the R327I mutant protein was 4.49% of the
      level of the WT in the conditioned medium, and the FIX:Ag of the R327I mutant
      protein in the conditioned medium and the cell lysates was 31.02% and 129.29%
      compared to that of WT, respectively. The mutation was characterized as cross
      reaction material reduced (CRMR). The viable cell fluorescent assays showed that
      the R327I protein was more in both the viable cells and in lysosome than that of
      WT. The FIX:C of the R327A, R327K, R327N and FIXbetaFVII mutants was reduced
      compared to that of WT, the reduction of FIX:C of FIXbetaFVII was the most
      significantly amount among all the mutants in medium. FIX:Ag of all the mutants
      in the medium, except that the R327K increased, was reduced. The result of
      Western blot showed that the molecular weight of R327I protein was the same as
      that of WT, but the amount of the protein was much less compared with WT in the
      conditioned medium. CONCLUSION: The abnormal synthesis and secretion as well as
      the abnormal function of the R327I mutant protein causes haemophilia B. The
      residue of R327 as well as the beta strand domain of R327 located play important
      roles of the specific function of FIX.

PMID- 23134861
TI  - [Expression of FOXP1 and cyclinE in primary central nervous system lymphoma and
      its significance].
AB  - OBJECTIVE: To evaluate the value of FOXP1 and Cyclin E gene in primary central
      nervous system lymphoma(PCNSL) of immunocompetent patients on prognostic
      significance. METHODS: Clinical data of 71 patients with newly diagnosed PCNSL
      from 2002 to 2007 was analyzed retrospectively. Immunohistochemistry method (HRP
      EnVision(TM)) was performed to observe the expression of FOXP1 and Cyclin E gene
      in tumor tissue samples. The survival was analyzed by Kaplan-Meier survival
      curve, survival factors analysis by the Log-rank test and COX proportional
      hazards regression model. RESULTS: FOXP1 positive was observed in 35 of 51
      patients (68.63%) and Cyclin E staining was present in 29 of 50 cases (58.00%).
      FOXP1(+) patients had a shorter overall survival (OS) than FOXP1(-) ones. 2-year
      OS rate in FOXP1(+) and FOXP1(-) patients were 23.33% and 73.56%, respectively(P
      = 0.0015). Cyclin E(+) patients had a shorter overall survival(OS) than cyclinE(
      ) ones. 2-year OS rate in Cyclin E(+) and Cyclin E(-) patients were 17.56% and
      69.76%, respectively (P = 0.0017). Multivariate analysis showed that Cyclin E
      expression was an independent prognostic factor for shorter OS (P = 0.048). FOXP1
      expression might be an important prognostic factor for shorter OS (P = 0.065).
      CONCLUSION: Cyclin E expression is an independent prognostic factor and FOXP1
      expression is a possible prognostic factor for poor clinical outcome in patients
      with PCNSL.

PMID- 23134862
TI  - [The changes of regulatory T cells and Th17 cells in a novel mouse severe
      aplastic anemia model].
AB  - OBJECTIVE: To explore the changes of regulatory T (Treg) cells and Th17 cells in
      a novel mouse severe aplastic anemia (SAA) model induced by interferon-gamma (IFN
      gamma) combined with busulphan (BU), and to demonstrate the rationality of the
      model in immunology level. METHODS: The BALB/c female mice SAA model was
      constructed by intraperitoneal injection with IFN-gamma and intragastric
      administration with BU (combined group), with BU group, IFN-gamma group and
      normal group as controls. After collecting the mononuclear cells in the
      peripheral blood (PB) and spleen of mice in each group, the percentage of
      CD4(+)CD25(+)FOXP3(+) Treg cells and Th17 cells in the mononuclear cells were
      detected by flow cytometry(FCM), and to analyze the changes. RESULTS: The
      percentage of the Treg cells in PB and spleen was (3.19 +/- 0.76)% and (4.77 +/-
      1.05)% respectively in combined group, being significantly lower than in other
      three groups (all P < 0.01). The percentage of the Th17 cells in PB and spleen
      was (2.07 +/- 0.12)% and (3.18 +/- 0.46)% respectively in combined group, being
      significantly higher than that in other three groups (P < 0.05 and 0.01,
      respectively). CONCLUSIONS: Lower Treg cells and higher Th17 cells was found in
      the novel mouse SAA model induced by IFN-gamma combined with BU, which
      demonstrates that this SAA model may be more close to the human immune-mediated
      marrow failure.

PMID- 23134864
TI  - [Identification of MYH9 gene mutation in a May-Hegglin anomaly family].

PMID- 23134863
TI  - [Study on the diagnostic value of lung biopsy in hematologic patients with lung
      infection].
AB  - OBJECTIVE: To evaluate the diagnostic value and safety of percutaneous lung
      biopsy in hematologic patients with lung infection. METHODS: 28 cases hematologic
      patients received CT-guided percutaneous lung biopsy when they developed a fever
      associated with pulmonary nodules or lumps in CT scan whose clinical diagnosis
      were unclear during or after chemotherapy. Sample of each lesion were drawn
      twice. The lung tissue was re-scanned after lung biopsy to check up in order to
      discover bleeding and pneumothorax. Biopsy tissue was examined by bacteria
      culture, acid-fast staining and pathology. Pathological examination contained HE
      staining, acid-fast stain, PAS stain, TB-DNA, methenamine silver and others.
      RESULTS: 28 cases contain 24 males and 4 females. Median age was 40 15 - 77 years
      old. Blood tests were as follows: 3 cases with HGB > 110 g/L, 9 with HGB 90 - 110
      g/L, 12 with HGB 60 - 89 g/L, 4 with HGB < 60 g/L. 8 with WBC > 10*10(9)/L, 6
      with WBC (4 - 10)*10(9)/L, 13 with WBC < 4*10(9)/L, 1 with WBC < 2*10(9)/L; 14
      with PLT > 100*10(9)/L, 5 with PLT (50 - 100)*10(9)/L, 5 with PLT < 50*10(9)/L, 4
      with PLT < 30*10(9)/L. 4 cases had mild extended PT, 3 mild extended APTT, 3 FIB
      lower than normal. Lung CT scans were as follows: 4 cases with simply lesion in
      right lung, 4 with simply lesion in left lung, 20 with lesions in bilateral lung.
      8 cases were diagnosed as fungal infection, 3 as tuberculosis infection, 1 as
      lung cancer, 1 as pulmonary infiltration of lymphoma, 1 as pulmonary infiltration
      of leukemia, and 14 as inflammatory changes with no specific diagnosis. 4 cases
      came with pneumothorax during lung biopsy, mild to moderate in 3 cases and severe
      in 1 case. Severe patient turned better after CT-guided suction. 3 cases with
      mild hemoptysis turned better after treatment. CONCLUSION: When hematopathy
      patients are with pulmonary nodules or lumps in CT scan whose clinical diagnosis
      is unclear, CT-guided percutaneous lung biopsy is safe and conducive to early
      diagnosis and conducive to early rehabilitation of patients if the coagulation
      function is basically normal and platelet count is not too low.

PMID- 23134865
TI  - [Acquired factor deficiency: a case report and literature review].

PMID- 23134866
TI  - [Detection of Abl kinase domain point mutations in chronic myeloid leukemia
      patients with imatinib resistance and its clinical significance].

PMID- 23134867
TI  - [Study on the normal reference range of white blood cell parameters from venous
      blood in 8876 cases of healthy Han population in plateau area].

PMID- 23134868
TI  - [The effect of Bcl3 overexpression on NFkappaB pathway in adult T cell leukemia
      cells].

PMID- 23134869
TI  - [Secondary acute leukemia after remission of patients with acute promyelocytic
      leukemia: 3 cases and literature review].

PMID- 23134870
TI  - [Diffuse alveolar hemorrhage after haploidentical hematopoietic stem cell
      transplantation: two cases report and literature review].

PMID- 23134871
TI  - [Thrombotic thrombocytopenic purpura after autologous stem cell transplantation:
      a case report].

PMID- 23134873
TI  - [B cells and graft-versus-host disease].

PMID- 23134872
TI  - [IgG4-related lymphadenopathy: a case report and literature review].

PMID- 23134874
TI  - [Hypofibrinogenemia and intracranial hemorrhage induced by valproic acid: a case
      report].

PMID- 23134875
TI  - [The biological feature of mesenchymal stem cells and its clinical applications
      in hematologic diseases].

PMID- 23134876
TI  - [Recent research progress on platelet apoptosis].

PMID- 23134877
TI  - [Mantle cell lymphoma in the era of targeted-therapy-in-depth report on American
      Society of Hematology 53rd annual meeting].

PMID- 23134878
TI  - [Chinese guidelines for the clinical application of antibacterial drugs for
      agranulocytosis with fever].

PMID- 23134879
TI  - Immunogenicity of monococcum wheat in celiac patients.
AB  - BACKGROUND: Research is intense to find wheat of low or null toxicity for
      patients with celiac disease (CD). Among candidates, there are diploid wheat
      species. OBJECTIVE: We compared the immunological properties of 2 lines of
      diploid monococcum wheat (Triticum monococcum ssp. monococcum), Monlis and ID331,
      with those of common wheat (Triticum aestivum). DESIGN: Interferon-gamma
      production and the proliferation of intestinal gliadin-specific T cell lines and
      clones were measured as evidence of T cell activation by peptic and tryptic (PT)
      digests of gliadins from 2 monococcum lines. Furthermore, organ cultures of
      jejunal biopsies from 28 CD patients were set up to assess the effects of PT
      gliadin on innate and adaptive immune response by using immunohistochemistry.
      RESULTS: Monlis and ID331 induced interferon-gamma production and proliferation
      in celiac mucosal T cells. In organ cultures, Monlis PT digest induced a
      significant increase of IL-15 epithelial expression and crypt enterocyte
      proliferation, whereas ID331 had no effect. Both monococcum lines caused
      intraepithelial T cell infiltration and lamina propria T cell activation.
      CONCLUSIONS: Our data show that the monococcum lines Monlis and ID331 activate
      the CD T cell response and suggest that these lines are toxic for celiac
      patients. However, ID331 is likely to be less effective in inducing CD because of
      its inability to activate the innate immune pathways.

PMID- 23134880
TI  - Individualized nutrition intervention is of major benefit to colorectal cancer
      patients: long-term follow-up of a randomized controlled trial of nutritional
      therapy.
AB  - BACKGROUND: In our published randomized trial in colorectal cancer, group 1 (n =
      37) received individualized nutritional counseling and education about regular
      foods, group 2 (n = 37) received dietary supplements and consumed their usual
      diet of regular foods, and group 3 (n = 37) consumed their usual diet of regular
      foods. Neither group 2 nor group 3 received individualized counseling. Early
      nutritional counseling during radiotherapy was highly effective at reducing acute
      radiotherapy toxicity and improving nutritional intake/status and quality of life
      (QoL). Efficacy persisted for 3 mo after the intervention. OBJECTIVE: The
      objective was to perform long-term follow-up in survivors of that clinical trial
      to specifically evaluate survival, late toxicity, QoL, and nutritional variables.
      DESIGN: Medical data were collected from patients' records, and prescheduled
      interviews were conducted by dietitians for individualized evaluations. Analyses
      and comparisons between groups (adjusted for stage) were performed after a median
      follow-up of 6.5 (range: 4.9-8.1) y. RESULTS: Patients complied with the
      Radiotherapy Department's follow-up protocol. Nutritional deterioration was
      higher (P < 0.001) in group 3 (n = 26) and group 2 (n = 29) than in group 1 (n =
      34). Adequate nutritional status was maintained in 91% of group 1 patients but
      not in any of the group 3 patients (P < 0.002). Intakes in group 1 were similar
      to reference values, and the patients adhered to the prescribed recommendations.
      Intakes in groups 2 and 3 were lower than recommended intakes: group 3 ? group 2
      < group 1 (P = 0.001). Median survival in group 3 was 4.9 y (30% died), in group
      2 was 6.5 y (22% died), and in group 1 was 7.3 y (only 8% died): group 3 > group
      2 > group 1 (P < 0.01). Late radiotherapy toxicity was higher in group 3 (n = 17;
      65%) and group 2 (n = 17; 59%) than in group 1 (n = 3; 9%): group 3 ? group 2 >
      group 1 (P < 0.001). QoL was worse in groups 3 and 2 than in group 1: group 3 ?
      group 2 < group 1 (P < 0.002). Worse radiotherapy toxicity, QoL, and mortality
      were associated with deteriorated nutritional status and intake (P < 0.001).
      Likewise, depleted intake, nutritional status, and QoL predicted shorter survival
      and late toxicity (HR: 8.25; 95% CI: 2.74, 1.47; P < 0.001). CONCLUSIONS: This
      study conveys novel information about the effectiveness of nutrition at improving
      long-term prognosis in colorectal cancer. Overall, the data indicate that early
      individualized nutritional counseling and education during radiotherapy is
      valuable for patients.

PMID- 23134881
TI  - Effect of fruit and vegetable consumption on immune function in older people: a
      randomized controlled trial.
AB  - BACKGROUND: Fruit and vegetable (FV) intake, which is often low in older people,
      is associated with reduced chronic disease risk. OBJECTIVE: We determined whether
      increased FV intake improves measures of immune function. DESIGN: We conducted a
      randomized controlled trial (The Ageing and Dietary Intervention Trial) in 83
      healthy volunteers aged 65-85 y with low FV intakes (<=2 portions/d); 82 subjects
      completed the intervention. Participants were assigned to continue their normal
      diets or to consume >=5 FV portions/d for 16 wk. At 12 wk, tetanus toxoid (0.5 mL
      intramuscular) and Pneumovax II vaccine (0.5 mL intramuscular; both vaccines from
      Sanofi Pasteur) were administered. FV intake was monitored by using diet
      histories, and biomarkers of nutritional status were assessed. The primary
      endpoint was the antibody response to vaccination. Specific antibodies binding to
      tetanus toxoid (total IgG) and pneumococcal capsular polysaccharide (total IgG
      and IgG2) were assessed at baseline and 16 wk. Participants were recruited
      between October 2006 and June 2008. RESULTS: The change in FV consumption
      differed significantly between groups [mean change in number of portions (95%
      CI): in the 2-portion/d group, 0.4 portions/d (0.2, 0.7 portions/d); in the 5
      portion/d group, 4.6 portions/d (4.1, 5.0 portions/d); P < 0.001)] and also in
      micronutrient status. Antibody binding to pneumococcal capsular polysaccharide
      (total IgG) increased more in the 5-portion/d group than in the 2-portion/d group
      [geometric mean (95% CI) of the week 16:baseline ratio: 3.1 (2.1, 4.4) and 1.7
      (1.3, 2.1), respectively; P = 0.005)]. There was no significant difference in the
      increases in antibody binding to tetanus toxoid. CONCLUSION: Increased FV intake
      improves the Pneumovax II vaccination antibody response in older people, which
      links an achievable dietary goal with improved immune function.

PMID- 23134882
TI  - Dietary intakes of carbohydrates in relation to prostate cancer risk: a
      prospective study in the Malmo Diet and Cancer cohort.
AB  - BACKGROUND: Dietary carbohydrates have been implicated in relation to prostate
      cancer. OBJECTIVE: Our objective was to examine the associations between dietary
      intakes of carbohydrates, fiber, and their food sources and risk of prostate
      cancer, overall and by case severity, in the Malmo Diet and Cancer cohort.
      DESIGN: The analysis included 8128 men aged 45-73 y without a history of cancer,
      cardiovascular disease, or diabetes and who were classified as adequate energy
      reporters. After a median follow-up time of 15 y, prostate cancer was diagnosed
      in 817 men. We used Cox proportional hazards regression to model associations
      between energy-adjusted nutrient and food intakes with risk of incident prostate
      cancer, with competing risk of death from non-prostate cancer causes taken into
      account. RESULTS: After adjustment for age and other known or potential risk
      factors, we observed no associations between total carbohydrates or dietary fiber
      and prostate cancer. We observed positive associations between the intake of low
      fiber cereals with overall and low-risk prostate cancer and between intakes of
      cake and biscuits and rice and pasta with low-risk prostate cancer (all P-trend <
      0.05). A high intake compared with zero consumption of sugar-sweetened beverages
      was associated with increased risk of symptomatic prostate cancer (HR: 1.38; 95%
      CI: 1.04, 1.84). CONCLUSIONS: Results from this large study with high-validity
      dietary data suggest that a high intake of refined carbohydrates may be
      associated with increased risk of prostate cancer. However we observed no
      significant associations with high-risk prostate cancer, and not all foods that
      are typically high in refined carbohydrates were associated with prostate cancer.

PMID- 23134883
TI  - Homocysteine, folate, vitamin B-12, and physical function in older adults: cross
      sectional findings from the Singapore Longitudinal Ageing Study.
AB  - BACKGROUND: There is a paucity of studies, as well as inconsistent findings, on
      the associations of homocysteine, folate, and vitamin B-12 with physical function
      and decline in older persons. OBJECTIVE: We investigated the independent
      associations of homocysteine, folate, and vitamin B-12 with gait and balance
      performance and Instrumental Activities of Daily Living (IADL) in community
      living older persons. DESIGN: We performed cross-sectional analyses on baseline
      data of 796 respondents in the Singapore Longitudinal Ageing Study who had
      laboratory measurements of fasting homocysteine folate and vitamin B-12 and
      completed Performance Oriented Mobility Assessment (POMA) of gait and balance and
      self-reports of IADLs. RESULTS: In multivariate analyses in which sex, age,
      education, housing type, comorbidities, hospitalization, depression and global
      cognitive scores, BMI, creatinine, arthritis and hip fracture, serum albumin and
      hemoglobin, and physical activities were controlled for, we showed that
      homocysteine, independently of folate and vitamin B-12, showed significant
      negative associations with POMA balance (P = 0.02), POMA gait scores (P < 0.01),
      and IADL (P < 0.01). Serum folate showed a significant positive association only
      with POMA balance scores (P < 0.045). No significant independent associations for
      vitamin B-12 were observed. CONCLUSIONS: The independent association of elevated
      homocysteine and low folate, but not vitamin B-12, on physical and functional
      decline was supported in this study. Interventional studies of the physical
      functional effects of folate and vitamin B-12 status in different populations are
      needed.

PMID- 23134885
TI  - Protein supplementation augments the adaptive response of skeletal muscle to
      resistance-type exercise training: a meta-analysis.
AB  - BACKGROUND: Protein ingestion after a single bout of resistance-type exercise
      stimulates net muscle protein accretion during acute postexercise recovery.
      Consequently, it is generally accepted that protein supplementation is required
      to maximize the adaptive response of the skeletal muscle to prolonged resistance
      type exercise training. However, there is much discrepancy in the literature
      regarding the proposed benefits of protein supplementation during prolonged
      resistance-type exercise training in younger and older populations. OBJECTIVE:
      The objective of the study was to define the efficacy of protein supplementation
      to augment the adaptive response of the skeletal muscle to prolonged resistance
      type exercise training in younger and older populations. DESIGN: A systematic
      review of interventional evidence was performed through the use of a random
      effects meta-analysis model. Data from the outcome variables fat-free mass (FFM),
      fat mass, type I and II muscle fiber cross-sectional area, and 1 repetition
      maximum (1-RM) leg press strength were collected from randomized controlled
      trials (RCTs) investigating the effect of dietary protein supplementation during
      prolonged (>6 wk) resistance-type exercise training. RESULTS: Data were included
      from 22 RCTs that included 680 subjects. Protein supplementation showed a
      positive effect for FFM (weighted mean difference: 0.69 kg; 95% CI: 0.47, 0.91
      kg; P < 0.00001) and 1-RM leg press strength (weighted mean difference: 13.5 kg;
      95% CI: 6.4, 20.7 kg; P < 0.005) compared with a placebo after prolonged
      resistance-type exercise training in younger and older subjects. CONCLUSION:
      Protein supplementation increases muscle mass and strength gains during prolonged
      resistance-type exercise training in both younger and older subjects.

PMID- 23134884
TI  - Genetic modifiers of nutritional status in cystic fibrosis.
AB  - BACKGROUND: Improved nutrition early in life is associated with better pulmonary
      function for patients with cystic fibrosis (CF). However, nutritional status is
      poorly correlated with the CFTR genotype. OBJECTIVE: We investigated the extent
      to which modifier genes influence nutrition in children with CF. DESIGN: BMI data
      were longitudinally collected from the CF Twin-Sibling Study and Cystic Fibrosis
      Foundation Patient Registry for twins and siblings from 2000 to 2010. A
      nutritional phenotype was derived for 1124 subjects by calculating the average
      BMI z score from 5-10 y of age (BMI-z(5to10)). The genetic contribution to the
      variation in BMI-z(5to10) (ie, heritability) was estimated by comparing the
      similarity of the phenotype in monozygous twins to that in dizygous twins and
      siblings. Linkage analysis identified potential modifier-gene loci. RESULTS: The
      median BMI-z(5to10) was -0.07 (range: -3.89 to 2.30), which corresponded to the
      47th CDC percentile. BMI-z(5to10) was negatively correlated with pancreatic
      insufficiency, history of meconium ileus, and female sex but positively
      correlated with later birth cohorts and lung function. Monozygous twins showed
      greater concordance for BMI-z(5to10) than did dizygous twins and siblings;
      heritability estimates from same-sex twin-only analyses ranged from 0.54 to 0.82.
      For 1010 subjects with pancreatic insufficiency, genome-wide significant linkage
      was identified on chromosomes 1p36.1 [log of odds (LOD): 5.3] and 5q14 (LOD:
      5.1). These loci explained >=16% and >=15%, respectively, of the BMI variance.
      CONCLUSIONS: The analysis of twins and siblings with CF indicates a prominent
      role for genes other than CFTR to BMI variation. Specifically, regions on
      chromosomes 1 and 5 appear to harbor genetic modifiers of substantial effect.

PMID- 23134886
TI  - Energy requirements in preschool-age children with cerebral palsy.
AB  - BACKGROUND: There is a paucity of data concerning the energy requirements (ERs)
      of preschool-age children with cerebral palsy (CP), the knowledge of which is
      essential for early nutritional management. OBJECTIVE: We aimed to determine the
      ERs for preschool-age children with CP in relation to functional ability, motor
      type, and distribution and compared with typically developing children (TDC) and
      published estimation equations. DESIGN: Thirty-two children with CP (63% male) of
      all functional abilities, motor types, and distributions and 16 TDC (63% male)
      aged 2.9-4.4 y participated in this study. The doubly labeled water method was
      used to determine ERs. Statistical analyses were conducted by 1-factor ANOVA and
      post hoc Tukey honestly significant difference tests, independent and paired t
      tests, Bland and Altman analyses, correlations, and multivariable regressions.
      RESULTS: As a population, children with CP had significantly lower ERs than did
      TDC (P < 0.05). No significant difference in ERs was found between ambulant
      children and TDC. Marginally ambulant and nonambulant children had ERs that were
      ~18% lower than those of ambulant children and 31% lower than those of TDC. A
      trend toward lower ERs with greater numbers of limbs involved was observed. The
      influence of motor type could not be determined statistically. Published
      equations substantially underestimated ERs in the nonambulant children by ~22%.
      CONCLUSIONS: In preschool-age children with CP, ERs decreased as ambulatory
      status declined and more limbs were involved. The greatest predictor of ERs was
      fat-free mass, then ambulatory status. Future research should build on the
      information presented to expand the knowledge base regarding ERs in children with
      CP. This trial was registered with the Australian New Zealand Clinical Trials
      Registry as ACTRN 12612000686808.

PMID- 23134887
TI  - Multiple micronutrient supplementation in Tanzanian infants born to HIV-infected
      mothers: a randomized, double-blind, placebo-controlled clinical trial.
AB  - BACKGROUND: Multiple micronutrients (vitamin B complex and vitamins C and E) were
      effective at reducing infectious disease morbidity, HIV disease progression, and
      poor pregnancy outcomes in HIV-infected women. OBJECTIVE: The objective was to
      evaluate whether direct supplementation of these micronutrients to HIV-exposed
      infants reduces mortality and morbidity. DESIGN: Infants born to HIV-infected
      women from Dar es Salaam, Tanzania, were randomly assigned to receive daily oral
      supplementation of multiple multivitamins (vitamin B complex and vitamins C and
      E) or placebo from age 6 wk for 24 mo. All-cause mortality, hospitalizations, and
      unscheduled clinic visits were recorded. Morbidities were recorded during monthly
      follow-up visits. All mothers received multiple micronutrients throughout the
      study. RESULTS: A total of 1193 infants were randomly assigned to receive
      micronutrients and 1194 to receive placebo. There were 138 child deaths in the
      multivitamin group and 124 deaths in the placebo group (HR: 1.13; 95% CI: 0.88,
      1.44; P = 0.33). Hospitalizations (RR: 0.83; 95% CI: 0.62, 1.13; P = 0.23),
      unscheduled clinic visits (RR: 0.97; 95% CI: 0.85, 1.10; P = 0.59), and maternal
      reports of diarrhea (RR: 0.97; 0.87, 1.10; P = 0.64) were not significantly
      different between the 2 groups. Fever (P = 0.02) and vomiting (P = 0.007) were
      significantly lower in the multivitamin group. Among 429 children whose mothers
      received antiretroviral (ARV) therapy, multivitamin use had no effect on
      mortality but was associated with a significant reduction in hospitalizations (P
      = 0.035), episodes of fever (P = 0.005), and episodes of fever and cough (P =
      0.019). CONCLUSIONS: In the setting of maternal micronutrient supplementation,
      supplementation of HIV-exposed infants with vitamin B and vitamins C and E does
      not reduce mortality. Studies of nutrition supplementation in ARV-exposed infants
      may be warranted.

PMID- 23134888
TI  - APOE genotype influences triglyceride and C-reactive protein responses to altered
      dietary fat intake in UK adults.
AB  - BACKGROUND: The response of plasma lipids to dietary fat manipulation is highly
      heterogeneous, with some indications that APOE genotype may be important.
      OBJECTIVE: The objective was to use a prospective recruitment approach to
      determine the effect of dietary fat quantity and composition on both lipid and
      nonlipid cardiovascular disease biomarkers according to APOE genotype. DESIGN:
      Participants had a mean (+/-SD) age of 51 +/- 9 y and a BMI (in kg/m2) of 26.0 +/
      3.8 (n = 44 E3/E3, n = 44 E3/E4) and followed a sequential dietary intervention
      (the SATgenepsilon study) in which they were assigned to a low-fat diet, a high
      fat high-SFA (HSF) diet, and the HSF diet with 3.45 g DHA/d (HSF-DHA), each for 8
      wk. Fasting blood samples were collected at the end of each intervention arm.
      RESULTS: An overall diet effect was evident for all cholesterol fractions (P <
      0.01), with no significant genotype * diet interactions observed. A genotype *
      diet interaction (P = 0.033) was evident for plasma triglycerides, with 17% and
      30% decreases in APOE3/E3 and APOE3/E4 individuals after the HSF-DHA diet
      relative to the low-fat diet. A significant genotype * diet interaction (P =
      0.009) was also observed for C-reactive protein (CRP), with only significant
      increases in concentrations after the HSF and HSF-DHA diets relative to the low
      fat diet in the APOE3/E4 group (P < 0.015). CONCLUSIONS: Relative to the wild
      type APOE3/E3 group, our results indicate a greater sensitivity of fasting
      triglycerides and CRP to dietary fat manipulation in those with an APOE3/E4
      genotype (25% population), with no effect of this allelic profile on cholesterol
      concentrations.

PMID- 23134889
TI  - Calcium intake is not associated with increased coronary artery calcification:
      the Framingham Study.
AB  - BACKGROUND: Adequate calcium intake is known to protect the skeleton. However,
      studies that have reported adverse effects of calcium supplementation on vascular
      events have raised widespread concern. OBJECTIVE: We assessed the association
      between calcium intake (from diet and supplements) and coronary artery
      calcification, which is a measure of atherosclerosis that predicts risk of
      ischemic heart disease independent of other risk factors. DESIGN: This was an
      observational, prospective cohort study. Participants included 690 women and 588
      men in the Framingham Offspring Study (mean age: 60 y; range: 36-83 y) who
      attended clinic visits and completed food-frequency questionnaires in 1998-2001
      and underwent computed tomography scans 4 y later in 2002-2005. RESULTS: The mean
      age-adjusted coronary artery-calcification Agatston score decreased with
      increasing total calcium intake, and the trend was not significant after
      adjustment for age, BMI, smoking, alcohol consumption, vitamin D-supplement use,
      energy intake, and, for women, menopause status and estrogen use. Multivariable
      adjusted mean Agatston scores were 2.36, 2.52, 2.16, and 2.39 (P-trend = 0.74)
      with an increasing quartile of total calcium intake in women and 4.32, 4.39,
      4.19, and 4.37 (P-trend = 0.94) in men, respectively. Results were similar for
      dietary calcium and calcium supplement use. CONCLUSIONS: Our study does not
      support the hypothesis that high calcium intake increases coronary artery
      calcification, which is an important measure of atherosclerosis burden. The
      evidence is not sufficient to modify current recommendations for calcium intake
      to protect skeletal health with respect to vascular calcification risk.

PMID- 23134890
TI  - Fatty acid patterns and risk of prostate cancer in a case-control study nested
      within the European Prospective Investigation into Cancer and Nutrition.
AB  - BACKGROUND: Fatty acids in blood may be related to the risk of prostate cancer,
      but epidemiologic evidence is inconsistent. Blood fatty acids are correlated
      through shared food sources and common endogenous desaturation and elongation
      pathways. Studies of individual fatty acids cannot take this into account, but
      pattern analysis can. Treelet transform (TT) is a novel method that uses data
      correlation structures to derive sparse factors that explain variation.
      OBJECTIVE: The objective was to gain further insight in the association between
      plasma fatty acids and risk of prostate cancer by applying TT to take data
      correlations into account. DESIGN: We reanalyzed previously published data from a
      case-control study of prostate cancer nested within the European Prospective
      Investigation into Cancer and Nutrition (EPIC) cohort. TT was used to derive
      factors explaining the variation in 26 plasma phospholipid fatty acids of 962
      incident prostate cancer cases matched to 1061 controls. Multiple imputation was
      used to deal with missing data in covariates. ORs of prostate cancer according to
      factor scores were determined by using multivariable conditional logistic
      regression. RESULTS: Four simple factors explained 38% of the variation in plasma
      fatty acids. A high score on a factor reflecting a long-chain n-3 PUFA pattern
      was associated with greater risk of prostate cancer (OR for highest compared with
      lowest quintile: 1.36; 95% CI: 0.99, 1.86; P-trend = 0.041). CONCLUSION: Pattern
      analyses using TT groupings of correlated fatty acids indicate that intake or
      metabolism of long-chain n-3 PUFAs may be relevant to prostate cancer etiology.

PMID- 23134892
TI  - Testing the safety of alternative wheat species and cultivars for consumption by
      celiac patients.

PMID- 23134891
TI  - Phosphatidylcholine supplementation in pregnant women consuming moderate-choline
      diets does not enhance infant cognitive function: a randomized, double-blind,
      placebo-controlled trial.
AB  - BACKGROUND: Choline is essential for fetal brain development, and it is not known
      whether a typical American diet contains enough choline to ensure optimal brain
      development. OBJECTIVE: The study was undertaken to determine whether
      supplementing pregnant women with phosphatidylcholine (the main dietary source of
      choline) improves the cognitive abilities of their offspring. DESIGN: In a double
      blind, randomized controlled trial, 140 pregnant women were randomly assigned to
      receive supplemental phosphatidylcholine (750 mg) or a placebo (corn oil) from 18
      wk gestation through 90 d postpartum. Their infants (n = 99) were tested for
      short-term visuospatial memory, long-term episodic memory, language development,
      and global development at 10 and 12 mo of age. RESULTS: The women studied ate
      diets that delivered ~360 mg choline/d in foods (~80% of the recommended intake
      for pregnant women, 65% of the recommended intake for lactating women). The
      phosphatidylcholine supplements were well tolerated. Groups did not differ
      significantly in global development, language development, short-term
      visuospatial memory, or long-term episodic memory. CONCLUSIONS:
      Phosphatidylcholine supplementation of pregnant women eating diets containing
      moderate amounts of choline did not enhance their infants' brain function. It is
      possible that a longer follow-up period would reveal late-emerging effects.
      Moreover, future studies should determine whether supplementing mothers eating
      diets much lower in choline content, such as those consumed in several low-income
      countries, would enhance infant brain development.

PMID- 23134894
TI  - Soft drinks, aspartame, and the risk of cancer and cardiovascular disease.

PMID- 23134893
TI  - beta-Carotene 15,15'-monooxygenase 1 single nucleotide polymorphisms in relation
      to plasma carotenoid and retinol concentrations in women of European descent.
AB  - BACKGROUND: Carotenoids have been hypothesized to reduce the risk of many
      diseases, but associations with intakes or blood concentrations may arise from
      other constituents of fruit and vegetables. Use of genetic variation in beta
      carotene 15,15'-monooxygenase 1 (BCMO1), a key enzyme in provitamin A carotenoid
      metabolism, as a surrogate for carotenoid exposure may aid in determining the
      role of carotenoids unconfounded by other carotenoid-containing food
      constituents, but important variants must be identified. OBJECTIVE: Our goal was
      to select BCMO1 single nucleotide polymorphisms (SNPs) that predict plasma
      carotenoid concentrations for use in future epidemiologic studies. DESIGN: We
      assessed the associations between 224 SNPs in BCMO1 +/- 20 kb imputed from the
      1000 Genomes Project EUR reference panel with plasma carotenoid and retinol
      concentrations by using 7 case-control data sets (n = 2344) within the Nurses'
      Health Study, randomly divided into training (n = 1563) and testing (n = 781)
      data sets. SNPs were chosen in the training data set through stepwise selection
      in multivariate linear regression models; beta-coefficients were used as weights
      in weighted gene scores. RESULTS: Two or 3 SNPs were selected as predictors of
      beta-carotene, alpha-carotene, beta-cryptoxanthin, and lutein/zeaxanthin. In the
      testing data set, the weighted gene scores were significantly associated with
      plasma concentrations of the corresponding carotenoid (P = 6.4 * 10-12, 3.3 * 10
      3, 0.02, and 1.8 * 10-17, respectively), and concentrations differed by 48%, 15%,
      15%, and 36%, respectively, across extreme score quintiles. CONCLUSIONS: SNPs in
      BCMO1 are associated with plasma carotenoid concentrations. Given adequate sample
      size, the gene scores may be useful surrogates for carotenoid exposure in future
      studies.

PMID- 23134895
TI  - Argon:  the 'lazy' noble gas with organoprotective properties.

PMID- 23134896
TI  - Case reports:  keep a critical eye!

PMID- 23134898
TI  - Giant ulcerating squamous cell carcinoma arising from linear porokeratosis: a
      case study.
AB  - Linear porokeratosis is one of the infrequent variants of porokeratosis, a rare
      disorder of keratinization that may develop into several epidermal malignancies,
      among them squamous cell carcinoma. Clinical surveillance for malignancy is
      imperative, but in cases when large or many lesions are present, surgical removal
      of porokeratosis lesions would result in an unfavorable amount of scarring. A
      case of a large, nonhealing full-thickness ulcer caused by a giant ulcerating
      squamous cell carcinoma occurring within lesions of long-standing linear
      porokeratosis is reported in a 43-year-old woman with a recent diagnosis of
      ulcerative colitis (UC). Wide excision of the ulcer and plastic surgical
      reconstruction of the area were performed. PET scans did not show metastases, so
      her prognosis is good based on definitive excision of the tumor. Physicians
      should be aware of this cutaneous disease and the importance of annual follow-up
      for these patients to monitor for any lesion that exhibits clinical features
      concerning for malignancy.

PMID- 23134899
TI  - An in vitro assessment of MRI issues at 3-Tesla for antimicrobial, silver
      containing wound dressings .
AB  - Although no reports of adverse events have been published to date, the presence
      of metallic dressing ingredients may present an magnetic resonance imaging (MRI)
      safety concern for patients using silver-containing wound dressings. The purpose
      of this in vitro study was to test magnetic field interactions (ie, translational
      attraction and torque), heating, artifacts, and conductivity (ie, electrical
      resistance) when using MRI at 3-Tesla for two (nonborder and border) silver
      containing wound dressings. The results indicated the dressings displayed no
      magnetic field interactions (deflection angle 0; no torque), and in each case,
      MRI-related heating effects were at the same levels as the background temperature
      increases (ie, <1.8C). The dressings created extremely subtle artifacts (one-for
      one relationship) on the MR images. With regard to the conductivity assessments,
      the average resistance values were 20 kOhm and 1.1 kOhm, respectively, for the
      nonborder and border wound dressings, which were acceptable levels. The findings
      show the two silver-containing wound dressings tested will not pose hazards or
      risks to patients and, thus, are considered "MR safe" according to the current
      labeling terminology used for medical products, and each dressing may be left in
      place when a patient undergoes an MRI examination. To date, only a hydrofiber
      silver-containing dressing has been tested for MRI safety. Because of potential
      variances in material characteristics, MRI test results are specific to the
      dressings tested and cannot be applied to other products. Future studies to
      define the level of silver concentration in dressings that may pose a hazard for
      performing an MRI are warranted.

PMID- 23134900
TI  - An in vitro quantification of pressures exerted by earlobe pulse oximeter probes
      following reports of device-related pressure ulcers in ICU patients  .
AB  - The earlobe often is used to monitor perfusion when pulse oximeter signal
      quality is impaired in the fingers and toes. Prompted by intermittent occurrences
      of roughly circular earlobe pressure ulcers among patients in intensive care
      units, a convenience sample of seven calibrated pulse oximeter probes was used to
      quantify earlobe pressure exerted by these devices in vitro. All were tested
      twice with an electronic load cell, a strain gauge with a transducer that
      transforms the measured force into a readable numerical signal. The probe was
      clipped to the load cell just as it is clipped to the earlobe in the clinical
      setting. The probes exerted an average of 0.24 lb (SD 0.6) of force over an area
      of 0.3 square inches, equal to an average of 20.7 mm Hg (SD 0.6) pressure on
      tissue. This value exceeds some empirically derived values of capillary perfusion
      pressure. The occurrence of device-related pressure ulcers, as well pressure
      ulcers on the ears, has been documented, but little is known about device-related
      earlobe pressure ulcers or the actual pressure exerted by these devices.
      Additional in vitro studies are needed to quantify the pressures exerted by these
      and other probes, and future prevalence and incidence studies should include more
      detailed pressure ulcer location and device use documentation. Until more is
      known about the possible role of these devices in the development of pressure
      ulcers, clinicians should be cognizant of their potential for causing pressure
      ulcers, particularly in patients whose conditions can compromise skin integrity.

PMID- 23134901
TI  - Ultrasonographic evaluation of morphologic pattern of amoebic liver abscess.
AB  - We evaluated sonographically 250 cases of amoebic liver abscess (ALA). Seventy
      eight percent (78%) of the ALA was located in the right lobe of the liver and 15%
      in the left lobe and rest of the abscesses occupied both lobes. ALA was round in
      50% and oval in 40% of the cases without significant wall echoes. Eighty eight
      percent (88%) of these were inhomogeneous. Twenty one percent (21%) of these
      lesions was contiguous with the liver capsule. Post therapy sonographic
      evaluation showed that there was complete resolution of the abscesses within one
      year in 90% cases, other showed residual abnormalities in the form of hypoechoic
      in 7% and hyperechoic in 3% cases. We concluded that serological and clinical
      data in combinations with these non specific sonographic features are sufficient
      for the management and follow up of ALA obviating the need for expensive and
      invasive techniques in most of the cases.

PMID- 23134902
TI  - Maternal serum zinc level and its relation with neonatal birth weight.
AB  - The present study was conducted in the Department of Obstetrics & Gynaecology,
      Mymensingh Medical College Hospital, Mymensingh and Molecular Microbiology &
      Central Laboratory of Bangladesh Institute of Nuclear Agriculture (BINA) from
      15th November 2007 to 31st May 2009 to find out the relation between maternal
      serum zinc level with neonatal birth weight. Hundred pregnant women who were
      advised to take 61.8 mg zinc daily throughout pregnancy were assigned to study
      group while the pregnant woman did not take zinc orally were allocated into
      control group. Serum zinc levels were measured between 37-42 weeks gestation and
      birth weight were measured just after delivery. Data were processed and analyzed
      using SPSS version 11.5. The test used to analyze the data was descriptive
      statistics, Chi-square probability test, Pearson correlation, unpaired t-test and
      odds ratio. A probability value of <0.05 was considered significant. Majority
      (97%) of the cases who received zinc during their antenatal period had normal
      serum zinc (>= 700MUg/L) level compared to only 22% of the control group woman
      who did not receive zinc. Normal birth weight of babies in pregnant woman who
      received zinc is 5.7 times higher than the pregnant woman who did not receive
      zinc. As the present study was a cross-sectional one, further study with large
      sample size and prospective design is recommended.

PMID- 23134903
TI  - Electrolyte changes in stroke.
AB  - The present study was carried out in the department of Neurology and Medicine,
      Mymensingh Medical College Hospital, Bangladesh during the period of January 2009
      to December 2010 to see the electrolyte changes in stroke. The serum
      concentration of Na+, K+, and Cl- were measured in 110 cases during acute period
      of stroke (55 ischemic and 55 haemorrhagic strokes). Data were analyzed by
      computer with SPSS programme using 't' test and chi square test. In haemorrhagic
      stroke, out of 55 patients 29(52.72%) had abnormal sodium level, of them
      23(41.8%) had hyponatremia, 6(10.9%) had hypernatremia. In contrast in ischemic
      stroke 23(41.80%) out of 55 had abnormal sodium level, of them 21(38%) had
      hyponatremia. The result showed that hyponatremia is almost equally common in
      both haemorrhagic and ischaemic group without significant difference (p>0.05).
      The study also revealed that hyponatremia is more common than hypernatremia in
      both groups. Mean +/- SD of age of the haemorrhagic group was 60.80 +/- 15.97
      while the age of ischaemic group was 59.89 +/- 15.84 years. Male, female ratio in
      haemorrhagic and ischaemic group 1:0.62 and 1:0.89 respectively. Mean +/- SD of
      serum Na+, K+, Cl- in haemorrhagic group were 136.18 +/- 10.5, 3.83 +/- 0.65,
      97.96 +/- 16.74 mmol/L, in ischaemic group 135.08 +/- 9.08, 4.00 +/- 0.75, 100.27
      +/- 8.39 mmol/L. The result showed no significant difference in haemorrhagic and
      ischemic stroke. Hyponatremia, hypokalamia and hyperchloredemia were more common
      than hypernatremia, hyperkalamia and hyperchloredemia. In haemorrhagic stroke,
      out of 55 patients, 21(38.18%) had abnormal potassium level, of them 19(34.55%)
      had hypokalemia, 2(3.63%) had hyperkalemia. In contrasts, in ischemic stroke, 15
      out of 55(27.22%) had abnormal potassium level. Of them 12(21.81%) had
      hypokalemia and 3(5.45%) had hyperkalemia. The finding showed that hypokalemia is
      almost equally common in both haemorrhagic and ischaemic group without
      significant difference. The study also revealed that hypokalemia is more common
      than hyperkalemia in both groups. In haemorrhagic stroke, out of 55 patients
      33(60%) had abnormal chloride level. Of them 20(36.4%) had hypochrloridemia,
      13(23%) had hyperchrloridemia, in contrast, in ischemic stroke, 40 out of 55(60%)
      had abnormal chloride level, of them 22(40%) had hypochrloridemia and 18(32.7%)
      had hyperchrloridemia. The result showed that changes in chloride level after
      haemorrhagic and ischemic stroke are similar. The result showed hypochrloridemia
      is more common than hyperchrloridemia in both groups.

PMID- 23134904
TI  - Comparative study of immunochromatographic assay (IgM) and widal test for early
      diagnosis of typhoid fever.
AB  - Typhoid fever is a severe systemic infection endemic in many developing
      countries, including Bangladesh. Present study evaluated immunochromatographic
      test (ICT) and Widal test in the early diagnosis of typhoid fever cases. The
      study was carried out in the department of Microbiology, Mymensingh Medical
      College, Mymensingh between July, 2010 and June, 2011, including 200 individuals
      of different age and sex. Of them, 150 were clinically suspected cases of typhoid
      fever and 50 age-sex matched controls. Among 150 blood samples from the suspected
      cases 106(70.7%) were positive for IgM of Salmonella typhi by ICT and 67(44.7%)
      were positive by Widal test. Whereas, among the 50 controls 4(8%) were positive
      by ICT and 6(12%) were positive by Widal test. The sensitivity, specificity,
      positive and negative predictive value of the ICT was found as 83.3%, 92.00%,
      91.9% and 83.6% respectively. On the other hand corresponding values for Widal
      test were of 44.4%, 88%, 80% and 59.5% respectively. Thus, The ICT (IgM) is
      better alternative to Widal test for early and accurate diagnosis of typhoid
      fever. The ICT (IgM) is rapid, easy to perform, applicable for field use and
      highly sensitive and specific for detection of antibodies in patients with
      typhoid fever.

PMID- 23134905
TI  - Prevalence of risk factors of chronic kidney disease in adults.
AB  - Chronic kidney disease (CKD) is an emergent public health burden. Its prevalence
      varies country to country, even in different professional and social groups in
      the same country. In Bangladesh there is no reported nationwide survey but there
      are some reports of survey in disadvantageous and advantageous population. In
      this study 125 CKD patients (cases) and 125 age and sex matched healthy subjects
      (control) in Mymensingh Medical College, a tertiary hospital of Bangladesh were
      compared for the presence of non-modifiable [age, sex, family history of
      hypertension (HTN), Cardiovascular disease (CVD), family history of kidney
      disease and Socioeconomic condition] and modifiable [HTN, Diabetes mellitus (DM),
      smoking habit, and obesity] risk factors. The mean age of control was 43.5 +/-
      6.3 years and the mean age of CKD cases was 44.7 +/- 12.7 years. Out of 125
      patients of CKD, males were 96 in number (76.8%) and females were 29 in numbers
      (23.2%). Most of the patients (52.8%) were in poor socioeconomic status while
      most of controls were from middle class (68.8%). Most of the participants were in
      stage-3 CKD [67.2%, creatinine clearance (Ccr):36.74 +/- 13.61 ml/min].
      Glomerulonephritis was the dominant cause of CKD (67.2%) followed by diabetes
      (24%), hypertension (4.8%) and others (4%). 72.8% of CKD patients were smokers.
      Among CKD, 86.4% participants had hypertension and 26.4% had diabetes. The
      difference of hypertension, diabetes and Body mass index (BMI) between case and
      control group is statistically significant (p<0.001). No statistically
      significant difference was found with risk factor like family history of kidney
      diseases. This emphasizes risk factor identification in general population to
      early diagnose CKD.

PMID- 23134906
TI  - Fasting glycaemic and lipidaemic status in acute coronary syndrome patients
      within 24 hours of onset of chest pain.
AB  - This is a descriptive type of cross sectional study done in Mymensingh Medical
      College Hospital during the period of June 2008 to November 2009 to estimate and
      analyze the fasting blood glucose (FBG) and fasting lipid profile of acute
      coronary syndrome (ACS) patients within 24 hours of onset of chest pain. Total 50
      patients of either sex diagnosed as acute coronary syndrome whose fasting blood
      sample would have been collected within 24 hours of chest pain were included.
      Among 50 patients 42(84%) were male and 8(16%) were female. Age range was 30-80
      years with a mean +/- SD of 50.74 +/- 12.05 years. Among 50 ACS patients, 9
      patients (18%) suffered from unstable angina (US), 2(4%) from non-ST segment
      elevation myocardial infarction (NSTEMI) and 39(78%) suffered from ST segment
      elevation myocardial infarction (STEMI). Study results revealed 41(82%) patients
      had euglycemia (70-110 mg/dl), 2(4%) patients had impaired fasting glucose (IFG)
      (110-125 mg/dl), and 7(14%) patients had hyperglycemia (>126 mg/dl). Dyslipidemia
      found in 38(76%) patients. Among them total cholesterol (TC) >200mg/dl in
      14(28%), decreased level of HDL-C (< 40 mg/dl in male and <50mg/dl in female) in
      22(44%), increased level LDL-C >= 130 mg/dl in 13(26%), and TG >150 mg/dl was
      found in 16(32%) patients.

PMID- 23134907
TI  - Enteropathogens associated with acute diarrhea in a tertiary hospital of
      Bangladesh.
AB  - Acute diarrheal diseases are great concern throughout the world, as they are
      responsible for considerable morbidity and mortality, especially in developing
      countries. The present study was carried out during the period from January' 2011
      to December' 2011 in the Department of Microbiology, Mymensingh Medical College.
      A total of 300 stool specimens were examined by standard laboratory methods for
      identification of enteropathogens. Rotavirus was detected by Polyacrylamide Gel
      electrophoresis (PAGE). Different diarrheagenic E. coli (DEC) were detected by
      Multiplex PCR following standard methods. Of the 300 stool specimens examined,
      Enteropathpgens were detected in 160(53.5%) cases. Rota virus was detected in
      82(27.5%) cases, followed by DEC in 54(18%), Shigella spp. in 8(2.4%), Salmonella
      spp. in 5(1.6%), Entameoba histolytica in 4(1.5%) and Giardia lamblia in 3(1.0%)
      cases. Among the DEC, the Enterotoxigenic E. coli (ETEC) was most prevalent (72%,
      39/54). The present study revealed a high prevalence of rotavirus and DEC as the
      predominant causes of diarrhea in this region.

PMID- 23134908
TI  - Weight of uterus in bangladeshi cadaver.
AB  - This cross sectional descriptive study was done to see the weight of uterus in
      Bangladeshi cadavers to increase the knowledge regarding variational anatomy in
      our country. Sixty post mortem specimens containing uterus, uterine tube, ureter
      and surrounding structures were collected by non random or purposive sampling
      technique from cadavers of different groups and fixed in 10% formol-saline
      solution. This study was carried out in the Department of Anatomy of Mymensingh
      Medical College, Mymensingh from July 2006 to June 2007. Gross and fine
      dissection was carried out to study the weight of uterus. In this study our
      findings were compared with those of the references. Maximum weight of the uterus
      was found in age group B (13 to 45 years). It is about 51.35 +/- 17.95 gm.

PMID- 23134909
TI  - Status of blood pressure among individuals consuming saline water.
AB  - Climate change is taking its toll in the form of saline water intrusion into the
      mainland of Bangladesh, which is one of the lowest-altitude countries in the
      world. The study was carried out with the objective to assess the blood pressure
      status associated with salinity in saline prone selected areas of Bagherhat and
      Tangail districts from March 2008 - June 2008 of rural Bangladesh. Two hundred
      and ninety subjects were selected purposively from both the districts. About 70%
      of the respondents were males and below forty years of age. More than two thirds
      of the respondents were illiterate; belong to 4-5 member family, with monthly
      family income of less than Tk. 4000 per month. Only one third of the respondents
      were smokers. More than two thirds of the respondents from salinity area had
      salinity level of 2-3%. Among them majority were drinking saline water for 6-10
      years and 26% were drinking for more than ten years. About 20% of the non saline
      respondents' systolic blood pressure was 110-120 mm of Hg and 26% of saline area
      had systolic blood pressure >135-140 mm of Hg. Mean systolic BP among salinity
      area was more than that for non salinity area. About 19% of the non saline
      respondents' diastolic blood pressure was <= 85 mm of Hg. About one third had >=
      90 mm of Hg, among them 31% were from saline area. Mean diastolic BP among
      salinity area was more than non salinity area. There was no history of heart
      disease, and less than 1% was diabetic among them. About two thirds had mean
      arterial pressure <70 mm of Hg, among them majority were from non saline area.
      About one third had >70 mm of Hg, among them majority were from saline area. The
      study concluded that systolic and diastolic blood pressures of saline group were
      significantly higher than that of the non saline group.

PMID- 23134910
TI  - Metabolic syndrome is a risk factor for development of heart failure in acute
      myocardial infarction.
AB  - There is a relationship between metabolic syndrome with heart failure. A case
      control study was designed to see the association of metabolic syndrome with
      heart failure. The study was conducted from August 2009 to May 2010. Hundred
      cases were selected as study population which was taken from Department of
      Cardiology Mymensingh Medical College, Mymensingh. Among them 50 were in Group A,
      50 were in Group B. Group A was the patient with acute myocardial infarction
      (AMI) with metabolic syndrome. Group B was the patient with AMI without metabolic
      syndrome. It revealed that 23(46%) in Group A and 10 (20%) in Group B developed
      heart failure. Which is statistically significant (p<0.05). The study concluded
      that metabolic syndrome is significantly associated with heart failure.

PMID- 23134911
TI  - Maternal and foetal risk factor and complication with immediate outcome during
      hospital stay of very low birth weight babies.
AB  - This prospective study was done to find out the maternal and foetal risk factors
      and complications during hospital stay. It was conducted in Special Care Neonatal
      Unit (SCANU), Department of Child Health, Bangabandhu Memorial Hospital (BBMH),
      University of Science and Technology Chittagong (USTC) from1st October 2001 to
      30th March 2002 and cases were 35 very low birth weight (VLBW) newborns. Common
      complications of VLBW babies of this series were frequent apnea (40%), Septicemia
      (25.71%), Hypothermia (17.14%), NEC (14.28%), Convulsion (11.43%), Hyper
      bilirubinaemia (8.57%), Anemia (5.71%), IVH (5.71%), RDS (2.86%), HDN (2.86%),
      CCF (2.86%), ARF (2.86%), either alone or in combination with other clinical
      conditions. Newborns 62.86% male, 37.14% female & their mortality rate were
      40.91% & 38.46% respectively; Preterm 88.57% & their mortality (41.93%) were
      higher than term babies (25.00%); AGA 62.86%, SGA 37.14% & mortality rate of AGA
      babies (45.46%) were higher than of SGA (30.77%) babies. The mortality rate of
      VLBW infants of teen age (<= 18 years) mothers (57.14%) & high (>= 30 years) aged
      mothers (50.00%) were higher than average (19-26 yrs) maternal age mothers
      (33.33%). Mortality rate was higher among the babies of primi (41.67%) than
      multiparous (36.36%), poor socioeconomic group (53.33%) than middle class
      (30.00%) & mothers on irregular ANC (47.83%) than regular ANC (25.00%). It has
      been also noted the mortality rate of home delivered babies (50.00%) higher than
      institutional delivered (34.78%) babies; higher in LUCS babies (46.15%) than
      normal vaginal delivered babies (31.58%); higher in the babies who had antenatal
      maternal problem (48.15%) than no maternal problems babies (12.50%); higher in
      the babies who had fetal distress (50.00%) and twin (46.67%) than no foetal risk
      factors (28.57%) during intrauterine life; higher in the babies who had problems
      at admission (46.67%) than no problems (35.00%); and mortality higher in twin
      (46.67%) than singleton babies (35.00%). Maximum VLBW babies who died during
      hospital stay had multiple problems and mortality was varied from ?60-100%. The
      babies who had frequent apnea have been carried relative better outcome
      (mortality rate 35.72%). In this study out of total 35 studied baby 21(60.00%)
      survived and 14(40.00%) died. Frequent apnea, sepsis, hypothermia, NEC,
      convulsion, jaundice, anemia, IVH, and RDS are common complications in VLBW
      babies. Male sex, prematurity, primiparity, average (middle) socio-economic
      status, irregular ANC, preterm labor, toxemia of pregnancy, prolonged rupture of
      membrane, malnutrition, multiple gestations and foetal distress are risk factor
      for VLBW delivery. Clinical outcome depends on maturity, birth weight, centile
      for weight, maternal age, parity, maternal nutrition & socio-economic status,
      ANC, place & mode of delivery, maternal problems during antenatal & perinatal
      period, number of gestation, fetal condition, presentation at admission,
      postnatal problems, time of start of management & referral and level of care.

PMID- 23134912
TI  - Effect of topical Beta blocker (Timolol maleate 0.5%) in primary open angle
      glaucoma.
AB  - The study was undertaken to measure the effects of Beta blocker (Timolol maleate
      0.5%) in moderate and advanced stage of primary open angle glaucoma by
      controlling intra-ocular pressure (IOP) and assessing the visual acuity (VA) and
      mean sensitivity (MS) of visual field. Study was done in the department of
      Ophthalmology, Bangabandhu Sheikh Mujib Medical University, Shahbagh, Dhaka from
      January 2002 to December 2005. It was a Prospective and interventional study.
      Thirty patients of bilateral primary open angle glaucoma were treated medically
      by B-blocker (Timolol maleate 0.5%) two times daily. Follow up were done after 7
      days, 1 month, 3 months and 6 months. Before treatment Intra ocular pressure
      (IOP) range was 22-30 mm of Hg (mean 23.40 +/- 2.04). After beta-blockers IOP
      reduced to the range of 10-20mm of Hg (mean 13.12 +/- 2.01) which was
      statistically significant (p>0.02) in moderate stage & 8-18 mm Hg (mean 13.50 +/-
      2.0) in advance stage which was also statistically significant (p<0.02). VA and
      MS also improved in 15 eyes (50%), remained unchanged in 9 eyes (30%) and
      deteriorated in 6 eyes (20%) in moderate stage and also improved in 15 eyes
      (50%), remained unchanged in 6 eyes (20%) and deteriorated in 9 eyes (30%) in
      advanced stage. Success rate was 80% in moderate (p>0.02) & 70% in advanced stage
      (p<0.02) and which was statistically significant.

PMID- 23134913
TI  - Association of positive thyroid auto antibodies with thyroid carcinoma.
AB  - The association between thyroid autoimmunity and thyroid cancer was carried out
      in a series of solitary thyroid nodules submitted to fine-needle aspiration
      cytology and subsequent histopathology. US guided FNACs were obtained from 295
      unselected consecutive patients with single thyroid nodules and positive (98) or
      negative (197) serum anti-thyroid antibody. Cytological results were classified
      in three classes of increased risk of malignancy: low risk (class II);
      indeterminate risk (class III); and suspect or malignant (class IV). A higher
      prevalence of class III (29.6%, p<0.05) and class IV (17.34%, p<0.05) and lower
      prevalence of class II (52.06%, p<0.01) were found in ATA+ nodules respectively.
      By multivariate logistic regression analysis ATA+ conferred a significant risk
      (odds ratio: 1.97 & 95% confidence interval: 0.97-3.97) for class IV cytology
      independently for age and sex. In 53 patients where thyroidectomy was carried
      out, thyroid cancer was found in (86.66%) patients with class IV nodules, in
      (19.4%) of class III nodules (all ATA-) and in none of 7 class II nodules.
      Histologically proven thyroid cancer (mostly papillary) was then observed in a
      higher proportion (13.2%) of ATA+, when compared with ATA- nodules (8.1%,
      p>0.01), but the significance of this finding is limited by the low number of
      class II nodules operated on. The presence of ATA+ confers an increased risk of
      suspicious or malignant cytology in solitary thyroid nodules.

PMID- 23134914
TI  - Varieties of foetal congenital abnormality.
AB  - The purpose of the study is to determine the type of fetal congenital
      abnormalities found among high risk pregnancies admitted in Fetomaternal Unit of
      Obs & Gynae Department in BSMMU. This is a cross sectional study done during the
      period July 2007 to June 2010. All the patients admitted with congenital
      abnormality in fetomaternal unit during this study period were included in this
      study. One hundred five cases had congenital abnormality of fetus among 1134
      deliveries. Out of which 46.66% had CNS abnormalities and 19.04% had renal
      abnormalities. Out of CNS abnormalities Hydrocephalous (40.81%) was the most
      common, 31.42% patients were of age between 20-24 years, 69.52% patients had
      parity between 1-3, 35.37% had deliveries >= 37 weeks, 69.52% patients had
      vaginal deliveries, 82.89% patients were terminated by prostaglandins, 96.19%
      patients had no drug history other than intake of iron and calcium, 26.67% babies
      had birth weight between 1.1-1.5 kg and 70.4% were of male babies. Advances in
      ultrasound technology have made possible the prenatal identification of an
      increasingly large number of fetal congenital malformations. Now fetal anatomical
      survey is performed routinely between 18 to 22 weeks.

PMID- 23134915
TI  - Safety of low molecular weight heparin in the treatment of cutaneous lichen
      planus.
AB  - An interventional study was undertaken to assess the safety of low molecular
      weight heparin in the treatment of lichen planus. Data were collected from the
      department of Dermatology and Venereology, Combined Military Hospital (CMH),
      Dhaka, Bangladesh for a period from July 2009 to June 2010. During the data
      collection period, thirty seven patients of lichen planus were assigned
      purposively. The mean age of the patients was 36 +/- 6.6 years and highest
      percentage of patients, 21(56.8%) were in between the 30-40 years old, majority
      of patients 32(86.5%) were male, two thirds of patients 24(64.9%) were married
      and majority of the patients 29(78.4%) were service holders. It was seen that
      about half of the patients 18(48.6%) had complaints of itching, maximum 12(32.4%)
      had involvement of shin area and 21(56.8%) suffered for a duration of 1 to 11
      months. The study revealed that 29(78.4%) patients yielded no side effect, while
      8(21.6%) developed local irritation 5(62.5%), bruises 2(25.0%) and headache
      1(12.5%). The side-effects however disappeared spontaneously without medication.
      The study suggests that low molecular weight heparin has excellent safety profile
      for treatment option of cutaneous lichen planus.

PMID- 23134916
TI  - To evaluate the extent of awareness about hazards of blood transfusion among the
      blood recipients.
AB  - This cross-sectional, observational study was carried out among the blood
      receiving patients conducted in the Department of Transfusion Medicine,
      Bangabandhu Sheikh Mujib Medical University from April 2008 to August 2009, over
      126 purposively selected, to evaluate the extent of awareness about hazards of
      blood transfusion among the blood recipient. In this study 74.1% of male and
      73.3% of female respondents had correct knowledge of blood transfusion (p>0.05).
      In literate group 85(91.4%) had knowledge about blood donation and transfusion
      compared to 8(8.6%) in illiterate group with significant statistical difference
      (p=0.001). Different misconception and lack of awareness about safe blood
      transfusion is present among people receiving blood and blood products.
      Illiterate persons have significant less level of knowledge about safe blood
      transfusion. So the number of educational programs on blood-donation should be
      expanded and transmitted to encourage possible receivers to take blood from
      nonprofessional volunteer donor and to carry out relevant screening tests before
      receiving blood products. Furthermore, they should know that all measures besides
      screening tests are implemented by blood banks to ensure that blood donation is
      safe for donors and that transfusion of the donated blood is safe for recipients.

PMID- 23134917
TI  - Serum zinc level and prostatic lesion.
AB  - To find out if there is any association of serum zinc level with different
      prostatic lesions like - benign prostatic hyperplasia (BPH), prostatic
      intraepithelial lesion (PIN) and frank prostatic carcinoma. Serum zinc level was
      measured by colorimetric method using RA50 semi autoanalyser from 49 patients
      having different prostatic pathology (BPH 13, PIN 31, carcinoma 5) and 30 age
      matched control who had no prostatic complaints. Statisticaly significant
      (p<0.01) gradual increased zinc level were found in patients having prostatic
      lesions. In BPH the serum (mean +/- SD) zinc level was 101 +/- 26.15, in low
      grade PIN 116 +/- 21.34, high grade PIN 117 +/- 20.95 and in frank prostatic
      carcinoma it was 139 +/- 11.09 MUgm/dl. Our results show statistical significant
      gradual increase of serum Zinc in BPH, PIN and frank prostatic carcinoma
      patients. Serum zinc level estimation can be routinely used as adjuvant for
      evaluation of prostatic lesion.

PMID- 23134918
TI  - Prevalence of impaired glucose tolerance among children and adolescents with
      obesity.
AB  - The study was undertaken to see the prevalence of impaired glucose tolerance
      among children and adolescents with obesity, attending the Paediatric Endocrine
      OPD, Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine
      and Metabolic disorders (BIRDEM), Dhaka, Bangladesh. A cross sectional study from
      January 2006 to December 2008 was conducted among obese children and adolescents
      (6-18 years). Children with any other endocrine disorder, dysmorphism/syndrome
      were excluded. Obesity was defined as BMI >= 95th percentile for age and sex
      using CDC growth chart. Children underwent two hours oral glucose tolerance test
      with 1.75 gm/kg or 75 gm of glucose, anthropometric and blood pressure
      measurement. Fasting serum insulin and lipid profile were measured. Impaired
      glucose tolerance (IGT) was defined as fasting plasma glucose (FPG) <7 mmol/L and
      2 hours post glucose load >= 7.8 mmol/L to <11.1 mmol/L. Diabetes mellitus (DM)
      was defined as FPG >= 7 mmol/L or 2 hours post glucose load >= 11.1 mmol/L.
      Homeostasis model assessment was used to estimate insulin resistance. A total of
      161 children presented with obesity. Male to female ratio was 1.3:1. Mean age was
      10.3 +/- 2 .5 years. Mean BMI was 27.86 +/- 4.1 kg/m2. IGT was found in 16.9% of
      children and adolescents. In children aged 6-10 years IGT was detected in 16.1%
      and in adolescents aged 11-18 years IGT was detected in 20%. Diabetes mellitus
      was detected in 2.1% of subjects, all were adolescents. Serum fasting insulin and
      hip circumference were significantly higher among children and adolescents with
      IGT compared to that of normal glucose tolerance. The high rate of IGT among
      obese children and adolescents is of concern. Factors contributing towards
      obesity needs to be identified and strategies should be planned for prevention
      and management of this health problem.

PMID- 23134919
TI  - Out come of induction of remission in undernourished children with acute
      lymphoblastic leukaemia.
AB  - Acute lymphoblastic leukaemia (ALL) is the most common childhood leukaemia. On
      the other hand under-nutrition is a common problem in our country. This
      prospective study was conducted to see the outcome of induction of remission in
      undernourished children with acute lymphoblastic leukaemia. This study was
      carried out in the department of Paediatric hematology and oncology of
      Bangabandhu Sheikh Mujib Medical University (BSMMU) during the period from
      November 2002 to October 2004. A total of sixty (60) children who were diagnosed
      as acute lymphoblastic leukaemia in 1 to 15 years of age were included in this
      study. But the children with previous history of congenital disease and that of
      chemotherapy or steroid were excluded from this study. Patients were divided into
      two groups on the basis of Z score of weight for age. Thirty (30) children those
      with Z score- 2 or less were classified as undernourished and was labeled as
      Group A and another thirty (30) patient those Z score above-2 were classified as
      well nourished and was placed in Group B, After inclusion into the study,
      completion of induction of remission was monitored by physical examination and
      laboratory investigations. The result showed that mean age in Group A was 77.16
      +/- 7.07 months and that in Group B was 74.13 +/- 5.09 months with male
      preponderance in both the groups. Mean body weight in Group A was 14.55 +/- 0.76
      Kg and that in Group B was 21.40 +/- 1.05 kg (p<0.001). Children in Group A
      required 39.06 +/- 0.72 days to complete induction but in Group B it required
      31.63 +/- 0.17 days (p<0.04). Hospital stay in Group A children was 52.10 +/-
      1.08 days and in Group B 42.37 +/- 0.50 (p<0.002). The result suggested that
      under nutrition has an influence on the out come of induction of remission in
      undernourished children with acute lymphoblastic leukaemia. So appropriate
      measures are essential to improve nutritional status of children for successful
      management of ALL in children.

PMID- 23134920
TI  - Ventral free oral mucous membrane graft for bulbar urethral stricture.
AB  - The use of oral mucous membrane graft onlay urethroplasty represents the most
      widespread method of bulbar urethral stricture repair. We investigated the short
      term result of oral mucous membrane graft placed on the ventral surface for
      management of bulbar urethral stricture. Patients with Bulbar urethral stricture
      of any length, infection free urinary tract and informed consent for oral mucosa
      harvesting and urethroplasty were selected for study. We enrolled 108 cases of
      bulbar urethral stricture patients from January 2004 to July 2009. The mean +/-
      SD preoperative maximum flow rate of 5.2 +/- 2.6 ml/sec and mean +/- SD PVR 87 +/
      58.3 ml were treated by substitution urethroplasty with oral mucous membrane by
      a single surgical team in a private hospital. Causes of stricture were trauma
      26(24.1%), infection 58(53.7%), catheter induced 8(7.4%), post TURP 11(10.2%) and
      unknown 5(4.6%). Oral mucous membrane was harvested from the cheek or from the
      inner side of lower lip. Defect of the urethra displayed by longitudinal ventral
      urethrotomy and the graft was sutured over the edges of the incised urethral
      mucosa over a 14 Fr latex Foley's catheter. Spongiosum tissue was closed over the
      graft. Pericatheter urethrogram was performed in all cases to check for the
      anastomotic leakage and the Catheter was removed after 2 weeks of the procedure.
      After removal of catheter uroflowmetry & ultrasound scan of bladder were
      performed to estimate the maximum flow rate and post voidal residue. The patient
      was followed-up every 3 months with uroflowmetry & ultrasonography. The median
      (range) age of the patients was 32(21-72) years. Mean follow up period was 36
      months (range 12-54). Mean +/- SD stricture length was 3.7 +/- 2.6 cm. The
      overall success rate was 91.7%. Mean +/- SD flow rate was 23 +/- 4.2 ml/sec, mean
      +/- SD post void residue was 25 +/- 15.5 ml and patient quality of life (QOL) was
      excellent in almost all patients. Overall complications were seen in 9(8.3%)
      cases. Of which, restricture occurred in 6 patients; periurethral fistulae seen
      in 2 cases and per urethral bleeding in 1 patient. No significant complications
      were observed at the donor site. Oral numbness and mild discomfort complained by
      67.6% patients which were managed by reassurance only. In our experience ventral
      placement of oral mucous membrane graft along with spongioplasty is a very easy
      procedure with very encouraging short term result.

PMID- 23134921
TI  - Coronary angiographic profile in bangladeshi patients with metabolic syndrome and
      ischemic heart disease.
AB  - The metabolic syndrome, which is characterized by a constellation of fasting
      hyperglycemia, hypertriglyceridemia, low HDL cholesterol, hypertension, and/or
      abdominal obesity, is a risk factor for the development of coronary artery
      disease (CAD) and cardiovascular events. We evaluated interrelationships between
      angiographic CAD and the metabolic syndrome, in 478 patients who were referred
      for coronary angiography to evaluate suspected myocardial ischemia in the
      department of cardiology of BSMMU between June 2007 and May 2008. We applied the
      criteria for the metabolic syndrome proposed by ATP III guideline. Study
      populations were divided into two groups on the basis of presence or absence of
      metabolic syndrome. Age was similar in both groups. Body mass index (BMI) was
      higher (26.22 +/- 1.94 vs. 22.07 +/- 1.55) in metabolic syndrome group (p <=
      0.0001). All parameters, waist circumference (103.16 +/- 10.21 vs. 91.45 +/-
      7.61) cm, blood pressure both systolic (141.34 +/- 21.49 vs. 127.94 +/- 13.01)
      and diastolic (86.8 5 +/- 8.42 vs. 79.28 +/- 7.77) mm of Hg, serum triglyceride
      (248.32 +/- 77.88 vs. 128.35 +/- 19.00)mg/dl, fasting blood glucose (125.40 +/-
      22.86 vs. 95.65 +/- 10.63)mg/dl were significantly higher in metabolic syndrome
      group (p value=0.0001), whereas HDL (33.10 +/- 6.55 vs. 39.30 +/- 6.17)mg/dl was
      lower (p value = 0.0001). More subjects in metabolic syndrome were having type B
      (55.60% vs. 31.00%) and type C (9.50% vs. 2.70%) lesion as compared to non
      metabolic syndrome group. Involvement of left main artery was more (4.80% vs.
      0.90%) in metabolic syndrome group. Metabolic syndrome has primary predictive
      ability for CAD. A metabolic profile should form part of the risk assessment in
      all patients with coronary disease, not just those who are obese.

PMID- 23134922
TI  - Urinary microalbumin as a risk factor for ischaemic stroke.
AB  - Microalbuminuria (MA), a microvascular irregularity of the blood - urine
      interface within kidney glomeruli, may reflect the renal sign of global
      endothelial dysfunction, and has been associated with an elevated risk of serious
      cardiovascular events including stroke. This case-control study was carried out
      in the Department of Neurology, Bangabandhu Sheikh Mujib Medical University
      (BSMMU), Dhaka, Bangladesh, from January 2008 to December 2009. This relationship
      appears graded with higher levels of microalbuminuria being independently
      associated with a greater magnitude of vascular risk over time. We studied 60
      patients of ischemic stroke with in 4 weeks of onset of symptoms and performed a
      case control study for MA by spot urinalysis. The incidence of microalbuminuria
      was 31.7% of the patients compared with 8.3% of the controls. Of all the
      traditional risk factors for stroke - age, male gender, hypertension, diabetes,
      dyslipidemia, smoking showed a positive correlation with the presence of MA
      (p<0.05). The effect of microalbuminuria and subtypes of ischemic stroke was
      observed that small vessels stroke (lacunar infract) were more (70%) than large
      vessels stroke (30%) and effect of microalbuminuria 21.67% higher in small
      vessels stroke than large vessels stroke. The presence of microalbuminuria
      appears to independently predict proper clinical outcome following acute stroke.

PMID- 23134923
TI  - Safety in use of cryotherapy and topical salicylic acid with lactic acid
      combination in treating verruca vulgaris.
AB  - An interventional study in the treatment of verruca vulgaris was conducted in
      sixty patients. This study conducted in the out-patient Department of Dermatology
      and Venereology, Chittagong Medical College Hospital, Chittagong, Bangladesh for
      duration of eight months (From January 2009 to September 2009). Thirty patients
      treated with cryotherapy, belonged to Group C and rest thirty patients treated
      with topical salicylic acid with lactic acid, belonged to Group D. The result
      showed that the  highest side effects immediately after therapy for Group C was
      burning 30(100%), then irritation 29(96.7%), erythema 28(93.7%), blister
      formation 28(93.7%) and pain 23(76.7%). On the other hand, highest side effect
      for Group D is irritation 29(96.7%), then burning 22(73.3%), pain 11(36.7%),
      pruritus 06(20%), blister formation 04(13%) and erythema 01(3.3%). Statistical
      significant difference was observed between Group C & Group D patients other than
      irritation. At 2nd visit, erythema 26(86.7%) was evidenced for Group C, whereas
      in Group D, there was irritation 16(53.3%). After 3rd visit in 4th week for Group
      C patients, there was burning 13(43.3%) but in Group D patients, hypo
      pigmentation 13(43.3%) was evidenced. On 4th visit in 6th week, hypo-pigmentation
      09(30%) was seen in Group C, while in Group D, pruritus and irritation were
      found. Statistical significant difference was observed between Group C & Group D
      respondents. Both treatments were associated with side-effects but these were
      higher with cryotherapy. The study recommends the combination of topical
      salicylic acid with lactic acid is safer than cryotherapy.

PMID- 23134924
TI  - Effect of maternal oral hydration therapy in oligohydramnios.
AB  - This was a randomized controlled trial on 64 pregnant women from 32 to 35 weeks
      gestation, in one year period to determine the effect of maternal hydration by
      oral water in oligohydramnios amniotic fluid index (AFI) <= 5. Studied women were
      randomly divided into two groups. Group A (intervention group) women were
      instructed to drink 2 liters of water within 2 hours and from the next day extra
      2 liters of water daily for 7 days. Group B (control group) women were allowed
      for routine water intake. AFI was done after 2 hours, 24 hours and 7 days of oral
      hydration therapy in both the groups. P values less than 0.05 was considered
      statistically significant. Pre-treatment mean AFI was 4.77 +/- 0.42 (mean +/- SD)
      vs. 4.80 +/- 0.43 (mean +/- SD) and post treatment AFI after 2 hours was 6.35 +/-
      0.65 vs. 4.81 +/- 0.42; after 7 days was 7.08 +/- 0.21 vs. 5.0 +/- 0.20 in oral
      hydration group and control group respectively. Delivery at 37-40 weeks was 53.1%
      vs. 12.4%, normal vaginal delivery in 71% vs. 21.8%, caesarean section in 29% vs.
      78.2% and low birth weight babies were 12.5% vs. 81.25% in intervention and
      control group respectively. Foetal outcome was healthy in 87.1% vs. 59.4%,
      asphyxiated in 12.9% vs. 50% and perinatal death was 3.22% vs. 21.8% between
      intervention and control group. Still born were 6.3% cases in control group.
      Maternal oral hydration therapy significantly increases the AFI, reduces the
      caesarean section rate and improves the foetal outcome.

PMID- 23134925
TI  - Total proctocolectomy with ileal pouch-anal anastomosis by stapling technique.
AB  - An ileal pouch-anal anastomosis (IPAA) has become the gold standard procedure for
      ulcerative colitis and familial adenomatous polyposis coli. Construction of an
      ileal pouch reservoir is now standard, usually in the form of J pouch. The aim of
      this study was to assess the outcome of ileal pouch-anal anastomosis by stapling
      technique after total proctocolectomy. This prospective observational study of
      six patients who underwent proctocolectomy followed by an ileal pouch-anal
      anastomosis by stapling technique. Whole colon and rectum was mobilized and
      resected; J pouch created by GIA device and pouch-anal anastomosis done by
      staplers. All patients were continent. Patients with familial adenomatous
      polyposis (FAP) and ulcerative colitis showed excellent outcome regarding their
      disease after proctocolectomy. The ileal pouch-anal anastomosis has become a
      feasible alternative to the conventional permanent ileostomy after total
      proctocolectomy. Satisfactory results have been reported, although the procedure
      is associated with considerable morbidity. Excision of all the affected mucosa is
      an essential part of the procedure. Our experience with the ileal pouch-anal
      anastomosis using stapling devices without mucosectomy.

PMID- 23134926
TI  - Guidelines and recommendations for studies on psychosocial aspects of patients
      with craniofacial anomalies.
AB  - In recent years there has been a few numbers of studies on psychosocial aspects
      of patients with craniofacial anomalies in the world. Current research
      surrounding psychological aspects of craniofacial anomalies suffers from various
      inconsistencies as reported by the results which may be due to differences in
      methodology that has made interpretation of findings very difficult. This article
      aims to present an evaluation of methodological errors and inconsistent findings
      in such studies. A thorough search based on electronic data base was done
      utilizing the following words: "craniofacial anomalies", "psychosocial impact".
      The resultant studies were evaluated based on the methodology and various
      lacunae, pitfalls were summed up. The results indicated that most of the studies
      suffer from various methodological errors. Several guidelines were fabricated so
      as to minimize error and maximize accuracy. The authors recommend these
      guidelines for future research design of studies related to psychosocial aspects
      of patients with craniofacial anomalies.

PMID- 23134927
TI  - A case of ileo-caecal Crohn's disease presenting as acute intestinal obstruction.
AB  - We report a case of 42 year old man who presented with one month history of
      weight loss, gradual abdominal distension and constipation. X-ray of the abdomen
      showed features of small gut obstruction. A tight stricture at the ileoceacal
      junction was found to be the cause of obstruction on laparotomy. Distal ileum was
      found to be severely inflammed with enlarged regional lymph nodes. Right
      hemicolectomy with resection of distal ileum was done. Histology revealed non
      caseating granuloma of Chroh's disease. Crohn's disease is relatively rare in
      Bangladesh. Recent data suggests rising incidence of Crohn's disease (CD) in the
      Indian sub-continent.

PMID- 23134928
TI  - Congenital duodenal web (wind-soak variety) in the fourth part of the duodenum
      causing obstruction in a female child.
AB  - Delayed presentation of Duodenal Obstruction is a great diagnostic dilemma due to
      non-specific, varied & wide spectrum presentation. In this study, a 6 years
      female child presented with recurrent, intermittent, colicky abdominal pain with
      bilious vomiting, and occasional constipation from 9 months of her age, without
      having any significant family history or associated condition. She was initially
      diagnosed as a case of recurrent small bowel obstruction due to atypical variant
      of malrotation. But, after laparotomy, she was finally diagnosed as a case of
      recurrent duodenal obstruction due to Congenital Duodenal Web (Wind-Soak Variety)
      with a central hole in the fourth part of the duodenum. After uneventful recovery
      of post operative period the patient was discharged at 7th postoperative day &
      followed up upto 3 months. She had been found alright without any complication.

PMID- 23134929
TI  - Morning glory syndrome.
AB  - A 20 years young boy came from Sherpur was admitted in the Department of
      Ophthalmology, Mymensingh Medical College Hospital, Mymensingh on 10th December
      2011 with the complaints of dimness of vision of right eye since childhood. His
      best corrected visual acuity right eye was 6/60 and left eye was 6/6. He has no
      strabismus or nystagmus. Fundus examination showed right eye - large disc with
      funnel shaped excavation surrounded by chorioretinal disturbance, white tuft of
      glial tissue on central part of disc, blood vessels emerge from rim of excavation
      in radial pattern. By clinical examination the patient was diagnosed as morning
      glory syndrome.

PMID- 23134930
TI  - Congenital urogenital sinus anomaly without Adrenal Hyperplasia.
AB  - Urogenital sinus anomaly is a mal-development of female urogenital system,
      usually associated with Congenital Adrenal Hyperplasia and may varied in
      presentation according to embryologic separation and length of sharing of common
      channel between vagina and urethra. We report a case of pure urogenital sinus
      anomaly of 2.5 years female child without any feature of Congenital Adrenal
      Hyperplasia or any other associated anomalies which is quite uncommon. The
      patient was diagnosed with thorough physical, biochemical, radiological and
      endoscopic evaluation. She had clitiromegaly, very poorly developed fused Labia
      minoras with a central hole, the length of common channel was about 2.5 cm and
      the level of vaginal confluence was at the mid portion of common channel. After
      in general counseling to parents, according to their desire she was operated. We
      performed Labialo-clitoro-vagino-urothroplasty and from post operative period to
      till now (after 3 months of operation) she is uneventful. Both functionally and
      cosmetically she is sound and her parents are also happy.

PMID- 23134932
TI  - Pseudomyxoma peritonei - a case report.
AB  - Pseudomyxoma peritonei (PMP) is rare in our clinical practice. The patient was a
      lady of 45 years admitted at the department of Obstetrics & Gynaecology in Sir
      Salimullah Medical College & Mitford Hospital (SSMC & MH) Dhaka with the
      complaints of swelling of the abdomen for 3 months associated with pain in the
      same region and weight loss. On examination a large swelling was palpated
      occupying the umbilical, hypogastric, both iliac, and part of both lumber
      regions. It was cystic, mildly tender, and immobile with ill defined margins.
      Computer tomography (CT) showed a cystic mass in the pelvic cavity extending upto
      the mid abdomen. Huge ascites was also noted. CT guided FNAC showed benign
      mucinous cystadenoma. Laparotomy was done which showed that the peritoneal cavity
      was filled up with mucinous material and there was a tumor in the right ovary
      which was free from adhesion. Left ovary and uterus were atrophic. Hysterectomy
      with bilateral salpingoophorectomy was done. Abdomen was cleared from the
      mucinous material as far as possible. Her postoperative recovery was uneventful.
      Histopathology report showed borderline mucinous cystadenoma of the ovary. She
      was referred to the oncology department. No chemotherapy was given but kept under
      follow-up.

PMID- 23134931
TI  - Budd-Chiari syndrome.
AB  - A 16 years old boy hailing from Comilla presented with sudden onset of upper
      abdominal pain, ascites and generalized muscle wasting for 3 months.
      Ultrasonogram (USG), Color Doppler and Venography was done and diagnosed him a
      case of Budd-Chiari syndrome. The patient was treated with salt and water
      restriction, diuretics, repeated palliative ascetic fluid aspiration with re
      accumulation within 1-2 days. He was also given Low molecular weight Heparin for
      7 days, overlapped and followed by warfarin 10mg/day with target INR 2.5-3.5.
      Consultation with hepatobiliary surgeon was done for shunt operation, but
      operation was not possible due to poor general condition. This patient improved
      satisfactorily with low molecular weight heparin, warfarin and supportive
      measures. Budd-Chiari syndrome is a rare veno-occlusive disorder involving
      hepatic vasculature.

PMID- 23134933
TI  - Successful pregnancy in a woman after repair of bladder exstrophy.
AB  - Exstrophy of bladder is a rare congenital anomaly. Pregnancy following surgical
      correction of bladder exstrophy occurred in this woman. Improved techniques in
      urinary diversion operation have enabled a large number of patients with bladder
      exstrophy to achieve urinary control. They can live fairly normal lives and some
      have achieved pregnancy. Case reports of such exist in the literature. The
      present case is based on the experience of a 28 years old lady who had successful
      pregnancy and delivery following curative repair of this defect one and a half
      year ago. A living healthy male baby was delivered by elective cesarean section.

PMID- 23134934
TI  - Leiomyoma of esophagus presenting as huge posterior mediastinal mass: 2 case
      reports.
AB  - Smooth muscle tumors presenting as mediastinal soft tissue masses are rare and
      are often mistaken for other neoplasms. Benign tumors of the esophagus account
      for fewer than 1% of all esophageal tumors, the most common of which are
      leiomyomas. They are frequently located in the lower third of the esophagus. We
      report two cases of esophageal leiomyoma in the thoracic esophagus which were
      firstly presented as huge mediastinal mass with intermittent dysphagia and
      radiologically flecks of calcification.

PMID- 23134935
TI  - Re-emergence Nipah - a review.
AB  - There was an outbreak of new emergence viral encephalitis caused by Nipah virus
      among humans in some areas of Bangladesh during 2001 - till to date. The disease
      affected mainly the young, had increased suspicion to spread from bat to man
      through eating of the same fruits. The risk of human-to-human transmission is
      thought to be low though many of the affected individuals belonged to the same
      family. The disease presented mainly as acute encephalitis with usually a short
      incubation period of less than two weeks, with the main symptoms of fever,
      headache, and giddiness followed by coma. Distinctive clinical signs include
      areflexia, hypotonia, hypertension, tachycardia and segmental myoclonus. Serology
      was helpful in confirming the diagnosis. Magnetic resonance imaging (MRI) showed
      distinctive changes of multiple, discrete or confluent small high signal lesions,
      best seen with fluid-attenuated inversion recovery (FLAIR) sequences. Mortality
      was as high as 32-92% and death was probably due to severe brainstem involvement.
      Relapse encephalitis was seen in those who recovered from acute encephalitis, and
      late-onset encephalitis was seen in those with initial non-encephalitic or
      asymptomatic diseases. Both these manifested as focal encephalitis arising from
      recurrent infection.

PMID- 23134936
TI  - Psychiatric and psychological comorbidities in patients with psoriasis- a review.
AB  - Psoriasis is a common inflammatory skin disease. The impact of psoriasis on
      quality of life is significant even when it involves relatively limited body
      surface area (BSA). Life stresses have been found as both a cause of psoriasis
      and as an aggravating factor in the disease. In different large epidemiological
      studies up to 79% patients of psoriasis had a negative impact on their lives, and
      Psoriasis was reported to be associated stressful life event in 10-90%,
      depression in 24-51%, felt shame and embarrassment over their appearance in 89%,
      lack of confidence in 42%, family friction in 26%, wish to be dead to active
      suicidal ideation in 9.7-5.5%, addiction and alcoholism in 18% and also
      significant impact upon sexual function. Children with psoriasis had 25-47%
      higher risk of developing any psychiatric disorder, 23-62% higher risk of develop
      depression and 32-250% higher risk of anxiety.

PMID- 23134937
TI  - Ethnicity and elevated liver transaminases among newly diagnosed children with
      type 2 diabetes.
AB  - BACKGROUND: To examine the influence of ethnicity on liver transaminases among
      adolescents with type 2 diabetes mellitus (T2DM). METHODS: A retrospective
      medical chart review of 57 (30 males and 27 females) newly diagnosed patients
      with T2DM. Ethnicity was determined by self-report and height, weight, body mass
      index (BMI) and glycosylated hemoglobin (HbA1c) were obtained using standard
      clinical procedures. Fasting levels of alanine aminotransaminase (ALT) and
      aspartate aminotransferase (AST) were collected prior to the initiation of any
      therapy. RESULTS: Age, gender, height, weight, BMI, and HbA1c did not differ
      between ethnic groups. Compared to African-Americans, Hispanics had significantly
      higher ALT (23.9 +/- 3.4 vs. 107.8 +/- 20.3, p=0.002) and AST (17.7 +/- 2.5 vs.
      71.1 +/- 15.7, p<0.001) and were significantly more likely to have ALT values
      above the upper limit of normal (20% vs. 71%, p=0.005) and twice the upper limit
      of normal (0% vs. 39%, p=0.05) as well as AST values above the upper limit of
      normal (0% vs. 53%, p=0.002). No differences in ALT or AST were found between
      Hispanics and non-Hispanic whites or between African-Americans and non-Hispanic
      whites. CONCLUSIONS: These preliminary findings suggest that Hispanic children
      with T2DM may be at higher risk for developing non-alcoholic fatty liver disease
      and indicate that a comprehensive hepatic evaluation is warranted in this
      population. Future studies that incorporate more precise and proximal measures of
      liver health are warranted in this population.

PMID- 23134939
TI  - Synthesis of MoO3 nanotubes by thermal mesostructural transition of spherical
      triblock copolymer micelle templates.
AB  - Here we report a new method of synthesizing one-dimensional metal oxide nanotubes
      (MoO(3)) via thermal mesostructural transition of spherical micelle templates.
      This nanotube formation is realized by entanglement of adjacent spherical core
      shell nanoparticles templated from block copolymer micelles.

PMID- 23134938
TI  - Lessons learned obtaining informed consent in research with vulnerable
      populations in community health center settings.
AB  - BACKGROUND: To improve equity in access to medical research, successful
      strategies are needed to recruit diverse populations. Here, we examine
      experiences of community health center (CHC) staff who guided an informed consent
      process to overcome recruitment barriers in a medical record review study.
      METHODS: We conducted ten semi-structured interviews with CHC staff members.
      Interviews were audiotaped, transcribed, and structurally and thematically coded.
      We used NVivo, an ethnographic data management software program, to analyze
      themes related to recruitment challenges. RESULTS: CHC interviewees reported that
      a key challenge to recruitment included the difficult balance between
      institutional review board (IRB) requirements for informed consent, and conveying
      an appropriate level of risk to patients. CHC staff perceived that the
      requirements of IRB certification itself posed a barrier to allowing diverse
      staff to participate in recruitment efforts. A key barrier to recruitment also
      included the lack of updated contact information on CHC patients. CHC
      interviewees reported that the successes they experienced reflected an alignment
      between study aims and CHC goals, and trusted relationships between CHCs and
      staff and the patients they recruited. CONCLUSIONS: Making IRB training more
      accessible to CHC-based staff, improving consent form clarity for participants,
      and developing processes for routinely updating patient information would greatly
      lower recruitment barriers for diverse populations in health services research.

PMID- 23134940
TI  - Evaluation of risk for type 2 diabetes mellitus in medical students using Indian
      Diabetes Risk Score.
AB  - BACKGROUND: According to World Health Organisation, type 2 diabetes mellitus
      [type 2 D. M] has recently escalated in all age groups and is now being
      identified in younger age groups. This underscores the need for mass awareness
      and screening programs to detect diabetes at an early stage. For this purpose we
      have used a simplified Indian Diabetes Risk Score (IDRS) for prediction of
      diabetes in undergraduate medical students. OBJECTIVES: To screen and to identify
      1st MBBS students at risk for developing type 2 D. M using IDRS. MATERIALS AND
      METHODS: 261 undergraduates (1st MBBS students) were scored using IDRS which
      includes age, family history of diabetes, exercise status, and waist
      circumference. After scoring them, we assessed random capillary blood glucose
      (RCBG) in students with high IDRS score. Students with RCBG >= 113 mg/dl are
      followed for definitive tests for diagnosis of prediabetes and diabetes. RESULTS
      AND CONCLUSION: We have assessed 261 students till now. It was observed that 5%,
      55%, and 38% students in High, Moderate, and Low risk group, respectively, for
      developing type 2 D. M. The mean abdominal obesity in high risk students was
      101.95 +/- 5.76 as compared to 79.17 +/- 11.08 in moderate and low risk students
      (P < 0.0001). 63% students were having sedentary lifestyle. Family history of
      diabetes in either or both parents was present in 25% students. Mean RCBG in
      students having score more than 50 was 97.33 +/- 9.68 mg/dl. Also, two students
      were having RCBG > 113 mg/dl in which one student found to have prediabetic.
      CONCLUSION: This underscores the need for further investigations to detect
      diabetes at an early stage and to overcome the disease burden of diabetes in
      future. Prevention of obesity and promotion of physical activity have to be the
      future plan of action which can be suggested in the form of regular exercise and
      diet planning for the students as part of an integrated approach.

PMID- 23134941
TI  - Pattern of rheumatic diseases in two outpatient clinics in Iran: similarities
      with some different features.
AB  - BACKGROUND: Rheumatic diseases are among the most prevalent diseases recognized
      in the world. Musculoskeletal disorders are one of the main causes of disability
      around the world and expend a large amount of health care and social resources
      and have a substantial impact on the quality of life of those affected. To
      identify preventable risk factors and to gain insights into the burden of the
      diseases, it is important to know the prevalence and demographics of them. Herein
      we are to describe the pattern of different rheumatic disorders and
      characteristics of the patients attending in rheumatology clinics in Yazd, Iran,
      with addressing some different points of views in this regards. MATERIALS AND
      METHODS: In this retrospective study, medical records of all patients referred to
      two main referral rheumatology clinics in Yazd from March 2009 to February 2010
      were reviewed. A questionnaire including sex, age, chief complaint, diagnoses,
      and co-morbid diseases was used for gathering the data. RESULTS: All medical
      records were reviewed, of whom 5187 patients had specific diagnoses. The mean age
      of the patients was 38.57 year +/- 19.4 SD. 70.81% were females and 29.19% were
      males. The most common diagnoses were: degenerative joint disease (58.33%),
      autoimmune disorders (17.88%), and soft tissue rheumatism (12.47%). The most
      frequent complaints were knee pain (32%). 55.6% of the patients were overweight
      (BMI >29) and 923 (17.8 %) of the patients had diabetes mellitus. CONCLUSION: Our
      findings were similar to other studies from Iran and the other countries in most
      features. The prevalence of autoimmune disorders was rather higher than the other
      studies; this is perhaps due to our belief that some of periarthritis conditions
      were part of systemic autoimmune diseases by careful history taking and using
      pertinent laboratory investigations.

PMID- 23134942
TI  - Carbapenem resistance and phenotypic detection of carbapenemases in clinical
      isolates of Acinetobacter baumannii.
AB  - BACKGROUND AND OBJECTIVES: Multidrug-resistant Acinetobacter baumannii (MDR-Ab)
      reported worldwide has become one of the most difficult nosocomially acquired
      Gram-negative pathogens to control and treat. The clinical utility of carbapenems
      is under threat with the emergence of acquired carbapenemases, particularly
      Ambler class B metallo-lactamases (MBL). Because of the global increase in the
      occurrence and dissemination of MBLs, early detection is critical. This study was
      undertaken to detect resistance to carbapenems in clinical isolates of A.
      baumannii from hospitalized patients by both disk-diffusion and minimum
      inhibitory concentration (MIC) methods and to assess the rate of carbapenemase
      and MBL production among the isolates. MATERIALS AND METHODS: A. baumannii were
      identified from various clinical samples and antibiotic susceptibility profile
      was determined by the standard disk-diffusion method. Meropenem-resistant strains
      were tested further by agar dilution MIC for meropenem. Resistant isolates were
      screened for carbapenemase production by the modified Hodge test and positive
      isolates were further checked for metallo-beta-lacatmase production by the EDTA
      disk synergy test. RESULTS: 42 isolates (31.81%) showed resistance to meropenem
      by the disk diffusion method. 47.6% were carbapenemase positive by the modified
      Hodge test and 19% were MBL producers phenotypically by the EDTA disc synergy
      test (EDS). These meropenem-resistant isolates were resistant to most of the
      other antibiotics tested. These 42 isolates were recovered mostly from patients
      admitted to intensive care units. Four isolates of the A. baumannii complex were
      pan drug resistant and showed resistance to even tigecycline and polymyxin B.
      CONCLUSION: Carbapenem resistance has been increasingly reported, necessitating
      their detection. This study reports simple, carbapenemase, and MBL detection
      method that can be easily incorporated into the daily routine of a clinical
      laboratory.

PMID- 23134943
TI  - Automated detection of malaria with haematology analyzer Sysmex XE-2100.
AB  - BACKGROUND: Diagnosis of malaria is usually made by microscopy [Giemsa, Acridine
      Orange (AO), and Quantitative Buffy Coat (QBC) assay], which requires expertise.
      Currently, automated haematology analyzers are being used for complete blood
      count (CBC), in all acute febrile and non-febrile illnesses which simultaneously
      detects malaria. The normal scattergram by the analyzer (Sysmex 2100) comprises
      of five parameters i.e. lymphocytes (pink), monocytes (green), neutrophils
      (blue), eosinophils (red) with a space between the neutrophil and eosinophil
      populations. AIMS: We carried out a prospective study to compare the efficacy of
      Sysmex XE-2100 (Sysmex Corporation, Kobe) for detection of malaria in comparison
      to other conventional techniques. MATERIALS AND METHODS: 430 cases were analyzed
      for malaria by microscopy (QBC, AO, Giemsa), ICT (Immunochromatography) and
      flowcytometric analyzer (Sysmex XE-2100). The abnormal scattergrams were observed
      as double neutrophil, double eosinophil, grey zone, extended neutrophil zone with
      a decrease space between eosinophil and neutrophil, and a combination of above
      patterns. RESULTS: Out of 70 positive cases [49/70 (70%) P. vivax, 18/70 (25.7%)
      P. falciparum, and 3/70 (4.2%) both P. vivax and P. falciparum], 52 showed
      abnormal scattergrams by the analyzer. The sensitivity and specificity of
      hematology analyzer found to be 74.2% and 88%, respectively. CONCLUSION:
      Flowcytometric analyzer is a rapid, high throughput device which needs less
      expertization for the diagnosis of malaria. Hence, it can be used in the
      diagnostic laboratories as an early modality for diagnosis of malaria in
      suspected as well as clinically in apparent cases.

PMID- 23134944
TI  - A cross sectional study of satisfaction of in-patients in a private medical
      college hospital in A.P.
AB  - OBJECTIVES: To study the level of satisfaction of in-patients and to find out the
      causes for dissatisfaction. MATERIALS AND METHODS: Study area--Pinnamaneni
      Siddhartha General Hospital. STUDY POPULATION: In-patients admitted in the
      Medicine, Surgery, Obstetrics and Gynecology, Orthopedics wards. SAMPLE SIZE:
      200. STUDY DESIGN: A well designed cross-sectional study using pre tested
      structural pro forma. Duration of study: 2 Months. Survey method: The sample size
      is randomly selected. Respondent is the patient. Patient satisfaction was
      assessed in relation to doctors, nurses, housekeeping and billing. The
      satisfactory levels were divided into Very good, Good, Fair, Bad, and Very bad.
      RESULTS: The satisfaction of in-patients expressed by majority was Good followed
      by Fair, Bad, Very good, and Very bad. The satisfaction expressed was more with
      nursing services followed by doctors and billing and least with housekeeping.

PMID- 23134945
TI  - Protein S deficiency in a case of superor sagital vein thrombosis.
AB  - Cortical vein thrombosis (CVT) is rare and is most common in the third decade of
      life. Cerebral venous thrombosis may be due to a variety of pathologic conditions
      like deficiencies of protein S (PS), antithrombin III, protein C, factor V
      Leiden, prothrombin gene mutations and hyperhomocysteinemia. Protein S is a
      vitamin K-dependent anticoagulant present in plasma and prevent thrombosis in
      association with protein C. Lack of it results in venous thromboembolism (VTE)
      rarely causing thrombosis of cerebral venous sinuses. Our patient is a 35-year
      old male who presented with focal seizures. MRI brain showed venous infarcts, and
      MR venogram showed extensive thrombosis of superior sagittal sinus. Later work up
      for hypercoagulable state showed significant Protein S deficiency.

PMID- 23134946
TI  - Rhinosporidiosis of lacrimal sac: a rare case report from North East India.
AB  - Rhinosporidiosis usually affects the mucous membrane of nose and conjunctiva,
      less frequently lacrimal sac, urethra, and skin. This is a case presentation of
      rare lacrimal sac rhinosporidiosis for the first time reported from the state of
      Tripura in North East India. Diagnosis of rhinosporidiosis is usually made by
      routine histological examination and treatment is surgical excision. It needs
      follow up as recurrence is common.

PMID- 23134947
TI  - Emergent cardiac surgery during transcatheter aortic valve implantation (TAVI): a
      weighted meta-analysis of 9,251 patients from 46 studies.
AB  - AIMS: Transcatheter aortic valve implantation (TAVI) is a novel treatment option
      for high surgical risk patients with severe symptomatic aortic valve (AV)
      stenosis. During TAVI, some patients may require emergent cardiac surgery (ECS).
      However, the incidence, reasons and outcomes of those needing ECS remain unknown.
      METHODS AND RESULTS: We performed a search of the English medical literature
      using MEDLINE to identify all studies on TAVI and evaluate the incidence of ECS
      (i.e., within 24 hrs of TAVI) and outcomes for these patients. Forty-six studies
      comprising 9,251 patients undergoing transfemoral, transapical or trans
      subclavian TAVI for native AV stenosis published between 01/2004 and 11/2011 were
      identified and included in this weighted meta-analysis. Overall, TAVI patients
      were old (mean=81.3+/-5.4 years) and had a high mean logistic EuroSCORE (24.4+/
      5.9%). Few patients required ECS (n=102; 1.1+/-1.1%) and this was marginally
      higher among those undergoing transapical TAVI as compared to those undergoing
      transarterial TAVI (1.9+/-1.7% vs. 0.6+/-0.9%). Data on the reasons for ECS were
      available in 86% (88/102 patients) and 41% of these (36/88) were performed for
      embolisation/dislocation of the AV prosthesis, with aortic dissection (n=14),
      coronary obstruction (n=5), severe AV regurgitation (n=10), annular rupture
      (n=6), aortic injury (n=14), and myocardial injury including tamponade (n=12)
      constituting the rest. Mortality at 30 days was about 9-fold higher in patients
      who did need as compared with those patients who did not need ECS (67.1+/-37.9%
      vs. 7.5+/-4.0%). CONCLUSIONS: Reported rates of ECS during TAVI were low with
      embolisation or dislocation of the prosthesis being the most common cause. ECS
      was associated with grave prognosis with two out of three patients dying by 30
      days. Thus, refinement in TAVI technology should not only focus on
      miniaturisation and improving flexibility of the delivery systems and/or devices 
      which may have the potential for decreasing aortic dissection, annular rupture,
      and tamponade- but also incorporate modifications to prevent
      embolisation/dislocation of the valve.

PMID- 23134948
TI  - Association between 9p21 genetic variants and mortality risk in a prospective
      cohort of patients with type 2 diabetes (ZODIAC-15).
AB  - The genomic region at 9p21 chromosome near the CDKN2A/CDKN2B genes is associated
      with type 2 diabetes(T2D) and cardiovascular disease(CVD). The effect of the 9p21
      locus on long-term mortality in patients with T2D has yet to be determined.We
      examined three single nucleotide polymorphisms (SNPs) on 9p21, consistently and
      independently associated with T2D (rs10811661) or CVD (rs10757278, rs2383206), in
      relation to the risk of total and cardiovascular mortality in diabetic patients.
      We also aimed to replicate the previously observed interaction between rs2383206
      and glycemic control on mortality.Genotypes for three SNPs were determined in 914
      individuals from a prospective cohort of T2D patients of Dutch origin.
      Associations with mortality were assessed using Cox proportional hazard
      analyses.After a median follow-up of 9.5 years, 358 out of 914 patients had died.
      The hazard ratio (HR) for total mortality among individuals homozygous for the
      T2D-risk allele of rs10811661 compared to non-homozygous individuals was
      0.74(95%CI 0.59-0.93). For the carriers of both CVD-risk alleles of rs10757278,
      the HR for total mortality was 1.31(95%CI 1.01-1.70). We found a significant
      interaction between rs2383206 and HbA1c on mortality, which was higher among
      patients with two CVD-risk alleles in the two lowest HbA1c tertiles (HR
      1.68(95%CI 1.08-2.63); HR 1.48(95%CI 1.01-2.18).In conclusion, common variants on
      9p21 were associated with mortality in patients with T2D in a Dutch population.
      The T2D SNP was inversely associated with mortality, while the CVD SNP increased
      the risk for mortality. We confirmed a possible, although different, synergistic
      relationship between HbA1c and rs2383206 on total mortality.

PMID- 23134954
TI  - [Pay attention to the detection of HBV drug resistance].

PMID- 23134953
TI  - [Study of vascular endothelial injury in male castrated rats].
AB  - OBJECTIVE: To explore the injury of vascular endothelium in male castrated rats.
      METHODS: A total of 30 eight-week-old adult male SD rats were randomly divided
      into 3 groups:control (n = 8); castration (n = 11) (low androgen) and replacement
      (n = 11) (androgen dosing after castration). After 10 weeks of treatment or
      castration, the rats were sacrificed to obtain aortic specimens. Arterial
      morphological changes were observed by hematoxylin and eosin staining and
      electron microscope. Endothelial cell chromatin degradation was detected by the
      assay of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL).
      The mRNA level of bcl-2 was analyzed by reverse transcription-polymerase chain
      reaction (RT-PCR). RESULTS: Compared with the control group, the arterial
      structure was disorderly and had shedding of endothelium in the castration group.
      More apoptotic endothelial cells were found in the castration group (61% +/- 20%)
      than the other two groups (P < 0.05). Compared with the control group, the bcl-2
      mRNA level decreased significantly in the castration group (P < 0.05). However no
      significant difference existed in the replacement group (P > 0.05). CONCLUSION:
      Low androgen may damage the structure of vascular endothelium in male castrated
      rats.

PMID- 23134955
TI  - [Relationship between serum hepatitis B virus DNA load and hepatocellular
      carcinoma in Qidong, China: a cohort follow-up study of 14 years].
AB  - OBJECTIVE: To explore the relationship between serum HBV DNA load and
      hepatocellular carcinogenesis in Qidong HBsAg carriers. METHODS: In 1997, 477
      HBsAg carriers and 477 age, gender and residence matched HBsAg negative controls
      were enrolled as a prospective cohort in Qidong city. The entry serum samples
      were detected for the levels of HBeAg and HBV DNA. The relationship between
      baseline HBV DNA load and hepatocellular carcinoma (HCC) during the follow-up
      period from June 1997 to June 2011 were analyzed. RESULTS: The total observed
      person-years (PY) were 12 200. Eighty-seven patients developed HCC with an
      incidence of 1498/100 000 PY in the HBsAg positive group versus 6 with an
      incidence of 94/100 000 PY (P = 0.000) in the HBsAg negative group. The relative
      risk (RR) was 15.96. N o significant difference existed between the incidences of
      other tumors in two groups (P = 0.161). Compared with the HBsAg negative group,
      the RR of HCC was 11.38 (95%CI 4.87 - 26.62, P < 0.01)in the HBsAg+/HBeAg- group
      and 29.08 (95%CI 12.37 - 68.37, P < 0.01) in the HBsAg+/HBeAg+ group; 5.80 (95%CI
      2.29 - 14.70, P < 0.01) in the HBsAg+/HBV DNA- group and 27.75 (95%CI 12.07 -
      63.81, P < 0.01) in the HBsAg+/HBV DNA+ group. In HBsAg positive subjects, while
      the HBV DNA load was classified into 5 levels namely 250 - 10(4), 10(4)-, 10(5)-,
      10(6)- and >= 10(7) copies/ml, the relative risks for HCC at each level were 2.84
      (95%CI 1.44 - 5.61, P < 0.01), 5.75 (95%CI 2.77 - 11.95, P < 0.01), 9.05 (95%CI
      4.71 - 17.41, P < 0.01), 6.39 (95%CI 2.79 - 14.64, P < 0.01) and 4.35 (95%CI 2.21
      - 8.56, P < 0.01) respectively versus the < 250 copies/ml group. CONCLUSION: HBV
      DNA is an important risk predictor of hepatocellular carcinoma. The HBsAg
      carriers with the serum loads of HBV DNA between 10(5) - 10(6) copies/ml are most
      likely to present with HCC.

PMID- 23134956
TI  - [Clinical analysis of hepatitis B virus mutations related to adefovir dipivoxil
      among patients with chronic hepatitis B virus infection in eastern Zhejiang
      province].
AB  - OBJECTIVE: To explore the clinical characteristics of hepatic B virus (HBV)
      mutations related to adefovir dipivoxil (ADV) among patients with chronic HBV
      infection in eastern Zhejiang province and provide some reference values on
      normative usage of antiviral drugs. METHODS: The data of chronic HBV-infected
      patients with HBV mutations related to ADV (n = 88) and non-mutation (n = 202)
      from June 2008 to August 2010 were analyzed retrospectively. The gene resistance
      mutations of HBV P region were analyzed by gene sequencing. And the HBV
      genotypes, HBV serum markers, HBV DNA levels and liver imaging findings were also
      analyzed. RESULTS: There were 9 cases with pre-existing mutations in 88 patients.
      The mutated sites were multiple and complicated. And the mutated sites related to
      other antiviral drugs were all accompanied by ADV-related mutations. The single
      mutated site was mostly at rtA181T (46.59%) and at rtV214A (11.36%). There were
      27 cases (30.68%) with >= two mutated sites. The constituent ratios of males, end
      stage liver diseases, complicated nonalcoholic fatty liver disease (NAFLD) and
      HBV genotype C infection in the mutation group were higher than those in the non
      mutation group (P < 0.01, < 0.01, 0.019, 0.045). The average ages in the mutation
      group were also higher than those in the non-mutation group (P < 0.001). But the
      constituent ratios of HBeAg positivity and the levels of HBV DNA were lower (P =
      0.002, 0.02). CONCLUSION: There may be some cases with pre-existing ADV-related
      mutations in ADV treatment-naive patients. The mutated sites occur at multiple
      loci, mostly at rtA181T and rtV214A. The male patients and those with a longer
      history of HBV infection, HBeAg negativity, HBV genotype C infection, illness
      progression and complicated NAFLD may be more susceptible to mutation. It is
      important for patients to accept and implement standardized regimens of antiviral
      drugs so as to prevent resistance and avoid salvage therapy.

PMID- 23134957
TI  - [Detection and significance of gene variation in hepatitis B virus S region].
AB  - OBJECTIVE: To explore the variations of gene S in hepatitis B viruses of
      hepatitis B patients and provide experimental evidences for the mutation analysis
      of viral gene. METHODS: The virus DNA load in hepatitis B patient donors was
      detected by real-time polymerase chain reaction (PCR) and gene sequence analysis.
      And a comparison was made with standard strain by the software DNAstar. RESULTS:
      (1) Gene S was successfully amplified and sequenced in 15 hepatitis B patients.
      Three samples had I->T mutation at residue 126 in HBsAg "a" antigenic
      determinant. (2) Sixteen hepatitis B patients had 67 nucleotide mutations,
      including 14 residues in PreS1 and 6 residues in PreS2. Mutations nt 3036 T->C,
      nt 3039 T->G, nt 3066 C->T and L88V existed in PreS1 gene in all samples.
      CONCLUSION: HBV genome is susceptible to nucleotide mutations. Some residues have
      geographically restricted mutations in gene S region. And understanding the
      significance of these mutations may help clarify the pathogenesis of hepatitis B
      and provide new experimental evidence for its gene diagnosis and prevention.

PMID- 23134958
TI  - [Correlation of the expression of NF-kappaB p65 and hepatic fibrosis in hepatitis
      patients].
AB  - OBJECTIVE: To explore the relationship between the expression of NF-kappaB p65
      and hepatic fibrosis in chronic hepatitis B (CHB) patients. METHODS: Sixty CHB
      patients with hepatic fibrosis underwent liver biopsy to determine the stages of
      liver fibrosis (S0-S4). The distribution and expression of collagens I, III and
      NF-kappaB p65 in different stages of fibrosis in liver tissue were observed by
      immunohistochemistry and the results analyzed statistically. RESULTS: The
      expression of NF-kappaB p65 was positively correlated with the stage of hepatic
      fibrosis. That was S4 > S3 > S2 > S1 (S0) (P < 0.01). And it was also positively
      correlated with the expression of collagens I and III (P < 0.01). CONCLUSION: The
      elevated expression of NF-kappaB p65 is closely associated with the occurrence
      and development of hepatic fibrosis. Its mechanism is probably related with the
      increased secretion of collagens I and III after the activation of hepatic
      stellate cell.

PMID- 23134959
TI  - [Effects of dexmedetomidine combined with fentanyl in patients undergoing
      anesthesia induction by sevoflurane].
AB  - OBJECTIVE: To investigate the effects of dexmedetomidine combined with fentanyl
      in patients undergoing anesthesia induction by sevoflurane. METHOD: Eighty
      patients for elective endotracheal intubation under general anesthesia operations
      were randomly and double-blindly divided into Dex combined with fentanyl group
      (Group DF) and the fentanyl group (Group F) from April 2011 to September 2011 at
      the Fourth Affiliated Hospital of Harbin Medical University, and there were 40
      cases in each group. The investigation was approved by all the patients and by
      the Ethics Committee of the hospital. In group DF, each patient was pumped in the
      0.5 ug/kg Dex by vein before 10 minutes of anesthesia induction and group F were
      given the same amount of normal saline, and tidal volume method was used to
      induce anesthesia of sevoflurane. All the patients were given 2 ug/kg fentanyl
      and 0.1 mg/kg vecuronium by tracheal intubation and the MAP and HR and adverse
      reactions were observed before anesthesia induction (T(0)), before endotracheal
      intubation (T(1)), at the moment of tracheal intubation (T(2)), after 1 minutes
      of tracheal intubation (T(3)), after 3 minutes of tracheal intubation (T(4)) and
      after 5 minutes of tracheal intubation (T(5)). RESULT: The loss of eyelash reflex
      time of group DF is shorter (P < 0.05), adverse reaction is less (P < 0.05) and
      the number of adding atropine case is higher than that of group F (P < 0.05), the
      MAP of the two groups after induction of other moments are lower than that of
      T(0) (P < 0.05); MAP of group F at T(1) is lower than that of T(0), T(2), T(3)
      and group DF (P < 0.05); T(1) of group DF is lower than that of T(0) (P < 0.05),
      the HR after induction of group DF is lower than that of T(0) and F group (P <
      0.05), and that of T(2) and T(4) are higher than that of T(1) (P < 0.05); HR of
      group F at T(1) is lower than that of T(2) and T(3) (P < 0.05). CONCLUSION:
      Dexmedetomidine in combination with fentanyl can inhibit stress response of
      tracheal intubation of sevoflurane induction efficiently and stabilize
      hemodynamics.

PMID- 23134960
TI  - [Effects of transcutaneous electrical stimulation of auricular Shenmen point on
      postoperative nausea and vomiting and patient-controlled epidural analgesia in
      cesarean section].
AB  - OBJECTIVE: To investigate the effects of transcutaneous electrical stimulation of
      auricular Shenmen point on postoperative nausea and vomiting and patient
      controlled epidural analgesia in cesarean section. METHODS: After IRB approval
      and informed consent, one hundred and eighty singleton primiparas undergoing
      elective cesarean section, in Qingdao Municipal Hospital, and Qingdao Hiser
      Medical Center, from November 2011 to March 2012, were randomly assigned to three
      groups: transcutaneous electrical stimulation of auricular Shenmen point group
      (group A, n = 60), transcutaneous electrical stimulation of auricular Eye point
      group (group B, n = 60) and control group (group C, n = 60). Women of group A
      received transcutaneous electrical stimulation of auricular Shenmen point
      (frequency 1.5 HZ) at the time of preoperation, 4, 10 and 22 hours of
      postoperation for 30 minutes. The strength was controlled by themselves. Women of
      group B received stimulation of auricular Eye point as group A. Women of group C
      received pressurization and connected line were the same with group A, but
      without electrical stimulation. The following indexes was observed: the incidence
      of postoperative nausea and vomiting (PONV) for 48 hours; the rate of
      metoclopramide; the visual analogue scale (VAS) score of rest pain, uterine
      contration pain and dynamic pain at the time of postoperation for 6, 12, 24 and
      48 hours (T(1)-T(4)); the total number and effective compressions number of
      patient-controlled epidural analgesia(PCEA);the dose of analgesia mixture; the
      anal exhaust time; the volume of postoperative bleeding for 6 hours of
      postoperation and the other side effects. RESULTS: Compared with group B and
      group C, the incidence of PONV, the rate of metoclopramide, the VAS score at the
      time T(1)-T(4), the total number and effective compressions number of PCEA, the
      ratio of the total number with effective compressions number and the dose of
      analgesia mixture were decreased in group A (P < 0.05), but no difference
      compared group B with group C (P > 0.05). The anal exhaust time and the volume of
      postoperative bleeding for 6 hours of postoperation were no difference in the
      three groups (P > 0.05). No other side effects were observed. CONCLUSION:
      Transcutaneous electrical stimulation of auricular Shenmen point can reduce the
      incidence of PONV and improves analgesia effect of PCEA in postoperation of
      cesarean section.

PMID- 23134961
TI  - [Change characteristics of regional cerebral blood flow and curative efficacy in
      patients with obsessive-compulsive disorder].
AB  - OBJECTIVE: To explore the change characteristics of regional cerebral blood flow
      (rCBF) and its correlation with curative efficacy in patients with obsessive
      compulsive disorder (OCD). METHODS: The images of rCBF and computed tomography
      (CT) were acquired from 30 OCD and 30 normal controls by single photon emission
      computed tomography (SPECT) and CT. The tomographic data of rCBF were normalized,
      smoothed and statistically processed with the statistical parametric mapping
      (SPM) software with two-sample Z-test. And the OCD grade was evaluated with the Y
      BOCS at pre- and post-medication. RESULTS: The abnormal results of CT were not
      found. The SPM Z-test showed that the sections of higher rCBF in the OCD patients
      were predominantly located in basal ganglia and occipital lobe compared with the
      normal controls (P < 0.001). The scores of Y-BOCS in 30 patients were markedly
      lower at post-medication than those at pre-medication (24 +/- 7 vs 11 +/- 6, P <
      0.001). At post-medication, the scores of Y-BOCS with higher rCBF in basal
      ganglia and occipital lobe were higher than those in basal ganglia or occipital
      lobe (P < 0.05). CONCLUSION: The OCD patients have higher rCBF in basal ganglia
      and occipital lobe. The curative efficacy of OCD with higher rCBF in basal
      ganglia and occipital lobe is worse than that in basal ganglia or occipital lobe.

PMID- 23134962
TI  - [Association between polymorphisms of Pen2 gene and late onset Alzheimer's
      disease].
AB  - OBJECTIVE: To explore the association between single nucleotide polymorphisms
      (SNPs) in Pen2 gene and late onset Alzheimer's disease (LOAD) in North Chinese
      population. METHODS: The genotypes of ApoE and Pen2 gene were determined by
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and
      direct sequencing respectively in 480 LOAD patients and 480 healthy controls. The
      strength of association between polymorphisms and AD was estimated with odds
      ratios (OR). RESULTS: The genotype of IVS2 + 335T < A was obtained. There was an
      association between IVS2 + 335T < A and apolipoprotein E (ApoE) genotypes (P =
      0.002). In the subjects with APOEepsilon 4 allele, there were significant
      differences in the distribution of alleles (P = 0.003) and genotypes (P = 0.007)
      between AD and control groups. The ORs (95% confidence interval (CI)) of allele A
      and T/A + A/A genotypes were 4.720 (1.517 - 10.654) and 3.886 (1.381 - 10.932)
      respectively with allele T and genotype T/T as references. CONCLUSION: An
      association exists between IVS2 + 335T < A and the development of LOAD in
      ApoEepsilon 4 carriers within the northern Chinese population. And allele A of
      Pen 2 gene may increase the risk for LOAD.

PMID- 23134963
TI  - [Surgical management of penetrating cervical vascular trauma].
AB  - OBJECTIVES: To discuss diagnosis and surgical management of penetrating cervical
      vascular trauma. METHODS: A retrospective clinical analysis of 22 penetrating
      carotid artery injuries. RESULTS: Twenty-two patients presented 32 vascular
      injuries, including innominate artery (n = 1), innominate vein (n = 2),
      subclavian artery (n = 6), subclavian vein (n = 2), common carotid artery (n =
      3), internal carotid artery (n = 3), external carotid artery (n = 4), jugular
      vein (n = 8) and vertebral artery (n = 4). There were 12 patients with stab
      wounds, 2 with blast wound and 8 with iatrogenic injuries. Of these, there were
      12 zone-1 injuries (38%), 19 zone-2 injuries (59%) and 1 zone-3 injury (3%). The
      distribution of 4 vertebral artery injuries were V1 (n = 1), V2 (n = 2) and V3 (n
      = 1). All patient received surgical and endovascular managements and got
      survival. CONCLUSIONS: Patients with penetrating cervical vascular injuries have
      high rate of mortality. Emergent surgical exploration is necessary for patients
      with hard signs of vascular injury such as hemodynamic instability,
      exsanguinating hemorrhage, or expanding hematoma. Those patients that are
      hemodynamically stable and who are without respiratory compromise should undergo
      further diagnostic imaging evaluation.

PMID- 23134964
TI  - [Analyses of relevant influencing factors in the treatment of tibial pilon
      fractures].
AB  - OBJECTIVE: To explore the relevant influencing factors of surgical outcomes for
      closed tibial pilon fractures. METHODS: From April 2005 to May 2011, 52
      consecutive closed tibial pilon fractures were treated by the same surgical team.
      There were 35 males and 17 females with a mean age of 40.0 years. According to
      the Ruedi-Allgower classification, the fracture types included type I (n = 13),
      type II (n = 22) and type III (n = 17). All patients were evaluated by the scores
      of American Orthopedic Foot and Ankle Society (AOFAS) and Burwell-Chamley.
      Postoperative complications were also recorded. The primary influencing factors
      of clinical outcomes were determined with regards to fracture types, reduction,
      complications and outcomes. RESULTS: The average follow-up period was 14.1 months
      (range: 6 - 28). The mean healing time was 5.5 months (range: 4.0 - 11). The
      reduction status: anatomical (n = 20), functional (n = 24) and poor (n = 8).
      Ankle function was excellent (n = 12), good (n = 26), fair (n = 9) and poor (n =
      5). Incidence of complication was 30.8% (n = 16), including incision skin
      necrosis (n = 5), superficial soft tissue infection (n = 4), deep infection (n =
      1) and posttraumatic arthrosis (n = 6). No significant differences (P > 0.05)
      existed in the occurrence of incision skin necrosis, superficial infection and
      deep infection between the outcomes of excellent/good and fair/poor groups while
      posttraumatic arthrosis rate had significant difference (P = 0.005) between two
      groups. The quality of reduction was an independent risk factor of final clinical
      outcomes. CONCLUSION: The quality of reduction, types of fracture and occurrence
      of posttraumatic arthrosis are risk factors of final outcomes for closed tibial
      pilon fractures.

PMID- 23134965
TI  - [Efficacies of arthroscopic debridement and olecranon fossa plasty in the
      treatment of osteoarthritis and posterior elbow impingement].
AB  - OBJECTIVE: To evaluate the efficacies of arthroscopic debridement and removal of
      osteophyma for olecroanon and olecranon fossa plasty for posterior impingement of
      elbow joint. METHODS: Between 1999 and 2008, a total of 21 cases were diagnosed
      with osteoarthritis and posterior elbow impingement. There were 15 males and 6
      females. And there were 16 right and 15 left cases. They included volleyball
      players (n = 7), tennis players (n = 7), golf enthusiasts (n = 4) and fencers (n
      = 3). The average duration of onset-operation was 3.5 years (range: 2.5 - 8).
      Arthroscopic exploration revealed synovial hyperplasia hypertrophy, cartilage
      degeneration and olecranon fossa hyperplasia with deformed olecranon fossa.
      Debridement and plasty were performed. Loose bodies were removed from elbow joint
      in 6 patients. Partial resection of posterior olecranon tip was performed and
      osteophytes or fibrous tissue removed in this area. Dynamic observation showed no
      posterior elbow impingement. RESULTS: Postoperative follow-up was conducted in 19
      cases and 2 cases became lost to follow-up. The average follow-up period was 25.3
      months (range: 18 - 42). All patients were evaluated preoperatively and
      postoperatively with the Hospital for Special Surgery Elbow Assessment Scale. The
      outcomes were excellent (n = 12), good (n = 7) and fair (n = 2). Postoperative
      patients elbow swelling and pain relieve, sports and life function returns to
      normal, elbow flexion and rotating mobility obviously improved. With the elbow
      radiological films to measure the range of motion, the average range of motion
      was 90.5 degrees  preoperatively and improved to 130 degrees  postoperatively.
      There was significant improvement in all cases. CONCLUSION: Posterior elbow
      impingement is caused by hyperextension trauma and elbow overuse during specific
      sporting activities. Arthroscopic debridement and olecroanon or olecranon fossa
      plasty demonstrates excellent results for posterior impingement of elbow joint.

PMID- 23134966
TI  - [The evaluation of Apneic anesthesia with intermittent ventilation for juvenile
      onset recurrent laryngeal papillomatosis].
AB  - OBJECTIVE: To evaluate the feasibility of Apneic anesthesia with intermittent
      ventilation (AAIV) during laryngeal papillomatosis removal in children. METHODS:
      The clinical data of 30 patients with laryngeal papillomatosis treated in the
      Tong Ren Hospital of Capital University of Medical Sciences, between 10 - 12 2011
      were analyzed. Thirty ASA physical status I or II patients who were scheduled for
      elective surgery. The patients were ventilated with 100% oxygen and the period of
      intermittent apnea were guided by pulse oximetry, the endotracheal tube was
      removed when SpO2 was 100% and reinserted when SpO2 was 95%. RESULT: The average
      duration of apnea was (232 +/- 32) s. This technique provided a good
      visualization and immobile field for operation. No significant complications have
      occurred with AAIV. CONCLUSION: Apneic anesthesia with intermittent ventilation
      could be used without any serious adverse outcome for juvenile-onset recurrent
      laryngeal papillomatosis, 232 seconds can provided for surgery every AAIV.

PMID- 23134967
TI  - [Roles of computed tomography in the diagnosis and treatment of complex atlas
      pillow deformity].
AB  - OBJECTIVE: To explore the roles of computed tomography (CT) in the diagnosis and
      treatment of complex atlas pillow deformity. METHODS: From January 2010 to
      February 2012, the preoperative and postoperative CT imaging findings were
      collected from 32 cases of complicated atlas pillow deformity undergoing surgical
      treatment at Henan Provincial People's Hospital. There were 18 males and 14
      females with a mean age of 36.8 years (range: 23 - 65). The average duration of
      disease was 4.5 years (range: 0.25 - 10). RESULTS: In 32 cases, a definite
      diagnosis was established preoperatively by coronary sagittal CT scans and 3
      dimensional reconstruction. And CT re-examinations were performed to review the
      postoperative curative efficacies. CONCLUSION: CT imaging examination is of vital
      importance in the diagnosis, personalized surgical procedures and prognostic
      evaluation of complex craniocervical junction deformity.

PMID- 23134968
TI  - [Multi-slice computed tomography diagnosis of collecting duct carcinoma].
AB  - OBJECTIVE: To explore the diagnostic features of collecting duct carcinoma (CDC).
      METHODS: A total of 7 CDC patients were retrospectively examined by multi-slice
      computed tomography (MSCT). The relevant diagnostic parameters were assessed.
      RESULTS: All lesions were located in renal medulla. Among them, infiltrations
      extended to renal calyx (n = 3) and cortex (n = 5). There were indistinct
      boundaries (capsule sign) on enhanced phase (n = 6) and pre-capsule (n = 1). On
      non-enhanced CT, CDC attenuation was greater than normal renal cortex or medulla
      (43.8 +/- 5.3 vs 37.6 +/- 5.1 or 32.6 +/- 4.1, P < 0.05). The degree of
      enhancement was less than normal renal cortex and medulla during all enhanced
      phases (P < 0.05 or 0.01). Excellent consistency existed between CT appearances
      of CDC and pathological characteristics. CONCLUSION: Dynamic contrast enhanced-CT
      can show distinct imaging features of CDC correlated with pathological
      characteristics so as to allow a better differential diagnosis.

PMID- 23134969
TI  - [Reversing paclitaxel-resistance of SKOV3-TR30 cell line by curcumin].
AB  - OBJECTIVE: To explore the effects of curcumin on paclitaxel resistance reversal
      of SKOV3-TR30 cell line and its mechanism. METHODS: The (3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide) MTT assay was performed to determine the
      sensitivity of curcumin-treated SKOV3-TR30 cells to paclitaxel. The cell cycle
      distribution of SKOV3-TR30 was analyzed by flow cytometry. And the expression
      level of glycogen synthase kinase-3 (GSK-3) protein was detected by Western blot.
      RESULTS: IC(50) of paclitaxel in SKOV3-TR30 decreased with a treatment of
      curcumin. And the reversal times was 3.0. Flow cytometric analysis of curcumin
      treated SKOV3-TR30 cells demonstrated a distinct G(2)-M phase block (78.5 +/-
      6.4)% after a 12-hour treatment of paclitaxel versus SKOV3-TR30 cells without
      curcumin. There was a lack of G(2)-M phase arrest (only 27.0% +/- 2.9%). The
      expression of GSK-3 protein in SKOV3-TR30 cells decreased with the 12 and 24-hour
      treatments of curcumin. CONCLUSION: Curcumin can partially reverse the paclitaxel
      resistance of SKOV3-TR30 cells through a down-regulation of GSK-3.

PMID- 23134970
TI  - Degradation of channelopsin-2 in the absence of retinal and degradation
      resistance in certain mutants.
AB  - Channelrhodopsin-2 is a light-gated cation channel from the green alga
      Chlamydomonas reinhardtii. It is functional in animal cells and therefore widely
      used for light-activated depolarization, especially in neurons. To achieve a
      fully functional protein, the chromophore all-trans-retinal is needed. It has not
      been investigated whether or not the apoprotein is stable without its cofactor
      until now. Here we show that channelopsin-2 (Chop2, protein without bound
      retinal) is much more prone to degradation than channelrhodopsin-2 (protein with
      retinal). Constructs of Chop2 fused to yellow fluorescent protein (Chop2::YFP) in
      the absence and presence of retinal confirm this observation by exhibiting
      strongly differing fluorescence. We present mutants of Chop2 with highly
      increased stability in the absence of retinal. Substitution of threonine 159 with
      aromatic amino acids causes enhanced resistance to degradation in the absence of
      retinal, which is confirmed by fluorescence intensity, the increase in
      photocurrents on the addition of retinal to previously expressed protein, and
      Western blot analysis. Exchanging threonine 159 with cysteine, however, increases
      photocurrents due to better binding of retinal, without obvious stabilization
      against degradation of the retinal-free opsin. We also show that the light
      activated hyperpolarizing chloride pump halorhodopsin from Natronomonas pharaonis
      (NpHR) is not prone to retinal-dependent degradation.

PMID- 23134971
TI  - Current cigarette smoking among adults - United States, 2011.
AB  - Tobacco use remains the single largest preventable cause of death and disease in
      the United States. According to the 2010 U.S. Surgeon General's report,
      approximately 443,000 U.S. adults die from smoking-related illnesses each year.
      In addition, smoking has been estimated to cost the United States $96 billion in
      direct medical expenses and $97 billion in lost productivity annually. To assess
      progress toward the Healthy People 2020 (HP2020) objective to reduce cigarette
      smoking by adults (objective TU-1.1),* CDC's Office on Smoking and Health used
      data from the 2011 National Health Interview Survey (NHIS) to estimate current
      national cigarette smoking prevalence. The findings indicate that 19.0% of adults
      smoked cigarettes in 2011 and no statistically significant change in current
      adult smoking prevalence occurred from 2010 (19.3%) to 2011 (19.0%). Among daily
      smokers, the proportion who smoked >=30 cigarettes per day (CPD) declined
      significantly, from 12.6% in 2005 to 9.1% in 2011, whereas the proportion of
      those who smoked 1-9 CPD increased significantly, from 16.4% to 22.0%. To help
      reduce the national prevalence of cigarette smoking among adults to the HP2020
      target of 12%, population-based prevention strategies (e.g., increasing prices of
      tobacco products, antitobacco media campaigns featuring graphic personal stories
      on the adverse health impact of smoking, smoke-free laws for workplaces and
      public places, and barrier-free access to help quitting) will need to be
      implemented more extensively. Such evidence-based tobacco control interventions
      can help adults quit and prevent the initiation of tobacco use.

PMID- 23134972
TI  - Energy drink consumption and its association with sleep problems among U.S.
      service members on a combat deployment - Afghanistan, 2010.
AB  - Beverages marketed as energy drinks have become a popular form of caffeine
      consumption targeted at young males, with some brands containing the caffeine
      equivalent of 1-3 cups of coffee or cans of soda. Energy drinks also include
      other ingredients intended to boost physical energy or mental alertness, such as
      herbal substances, amino acids, sugars, and sugar derivatives; however, caffeine
      is the main active ingredient. Approximately 6% of adolescent and young adult
      males in U.S. civilian and military populations consume energy drinks daily.
      These products generally are unregulated and can have negative side effects
      (e.g., caffeine intoxication, overdose, withdrawal, and poor interactions with
      alcohol). Paradoxically, excess consumption also can increase sleep problems and
      daytime sleepiness, which can impair performance. To determine the extent of
      energy drink use and the association with sleep problems and sleepiness during
      combat operations, Walter Reed Army Institute of Research analyzed data collected
      by Joint Mental Health Advisory Team 7 (J-MHAT 7) to Operation Enduring Freedom
      in Afghanistan in 2010. The analysis showed that 44.8% of deployed service
      members consumed at least one energy drink daily, with 13.9% drinking three or
      more a day. No differences by age or rank were found. Service members drinking
      three or more energy drinks a day were significantly more likely to report
      sleeping <=4 hours a night on average than those consuming two drinks or fewer.
      Those who drank three or more drinks a day also were more likely to report sleep
      disruption related to stress and illness and were more likely to fall asleep
      during briefings or on guard duty. Service members should be educated regarding
      the potential adverse effects of excessive energy drink consumption on sleep and
      mission performance and should be encouraged to moderate their energy drink
      consumption in combat environments.

PMID- 23134973
TI  - Progress toward poliomyelitis eradication - Nigeria, January 2011-September 2012.
AB  - In 1988, the World Health Assembly launched the Global Polio Eradication
      Initiative (GPEI) and, in 2012, declared the completion of polio eradication a
      programmatic emergency for global public health. To date, wild poliovirus (WPV)
      cases reported worldwide in 2012 are at historically low levels. Nigeria is one
      of only three countries with uninterrupted WPV transmission (in addition to
      Pakistan and Afghanistan) and has been the origin of WPV imported into 25
      previously polio-free countries since 2003. This report updates previous reports
      and describes polio eradication activities and progress in Nigeria during January
      2011-September 2012, as of October 30, 2012. The number of reported WPV cases
      increased from 21 in 2010 to 62 in 2011. During January-September 2012, a total
      of 99 WPV cases were reported, more than doubling from the 42 cases reported
      during the same period in 2011. During 2011, a total of 32 circulating vaccine
      derived polio virus type 2 (cVDPV2) cases were confirmed; six cVDPV2 cases were
      confirmed during January-September 2012, compared with 18 cVDPV2 cases during the
      same period in 2011. Nigeria's 2012 Polio Eradication Emergency Plan includes
      senior government leadership oversight, new program management and strategic
      initiatives, an accountability framework, and a surge in human resources to
      address chronically missed children during supplemental immunization activities
      (SIAs).* In 2012, indicators of immunization campaign quality show modest
      improvements; available data indicate gaps in surveillance. Continuing WPV
      transmission in Nigeria poses an ongoing risk for WPV reintroduction and
      outbreaks in polio-free countries and is a major obstacle to achieving global
      eradication.

PMID- 23134974
TI  - Notes from the field: carbon monoxide exposures reported to poison centers and
      related to hurricane Sandy - Northeastern United States, 2012.
AB  - Hurricane Sandy made landfall as a post-tropical cyclone along the coast of
      southern New Jersey on Monday, October 29, 2012. In the wake of Sandy, state and
      federal public health agencies have observed an increase in the number of
      exposures to carbon monoxide (CO) reported to poison centers. CO is imperceptible
      and can cause adverse health effects ranging from fatigue and headache to
      cardiorespiratory failure, coma, and death. CO poisoning is a leading cause of
      mortality and morbidity in post-disaster situations, when widespread power
      outages occur and risky behaviors, such as improper placement of generators and
      indoor use of charcoal grills, increase.

PMID- 23134975
TI  - Influence of solution chemistry on Cr(VI) reduction and complexation onto date
      pits/tea-waste biomaterials.
AB  - Tea waste (TW) and Date pits (DP) were investigated for their potential to remove
      toxic Cr(VI) ions from aqueous solution. Investigations showed that the majority
      of the bound Cr(VI) ions were reduced to Cr(III) after biosorption at acidic
      conditions. The electrons for the reduction of Cr(VI) may have been donated from
      the TW and DP biomasses. The experimental data obtained for Cr(VI)-TW and Cr(VI)
      DP at different solution temperatures indicate a multilayer type biosorption,
      which explains why the Sips isotherm accurately represents the experimental data
      obtained in this study. The Sips maximum biosorption capacities of Cr(VI) onto TW
      and DP were 5.768 and 3.199 mmol/g at 333 K, respectively, which is comparatively
      superior to most other low-cost biomaterials. Fourier transform infrared
      spectroscopic analysis of the metal loaded biosorbents confirmed the
      participation of -COOH, -NH(2) and O-CH(3) groups in the reduction and
      complexation of chromium. Thermodynamic parameters demonstrated that the
      biosorption of Cr(VI) onto TW and DP biomass was endothermic, spontaneous and
      feasible at 303-333 K. The results evidently indicated that tea waste and date
      pits would be suitable biosorbents for Cr(VI) in wastewater under specific
      conditions.

PMID- 23134976
TI  - Radiofrequency ablation plus chemoembolization versus radiofrequency ablation
      alone for hepatocellular carcinoma:  a meta-analysis of randomized-controlled
      trials.
AB  - BACKGROUND: There is a continuing debate on whether transcatheter arterial
      chemoembolization (TACE) plus radiofrequency ablation (RFA) is more effective
      than RFA alone in the treatment of patients with hepatocellular carcinoma (HCC).
      We carried out this meta-analysis of randomized-controlled trials to provide
      greater clarity on whether RFA plus TACE was more effective than RFA alone for
      HCC. METHODS: A literature search was carried out for all possible randomized
      controlled trials. The outcomes were overall survival rates and major
      complications. Data were abstracted using standardized forms, and an overall
      rating of the quality of evidence was assigned using the GRADE (Grading of
      Recommendations Assessment, Development, and Evaluation) criteria. We estimated
      summary odds ratio (OR) with its 95% confidence interval (95% CI) to assess the
      effects. RESULTS: Seven randomized-controlled trials were included. Meta-analysis
      showed that RFA plus TACE significantly improved the survival rates of patients
      with HCC at 1 and 3 years (for the one-survival rate, fixed-effects OR=2.71, 95%
      CI 1.65-4.43, P<0.0001; for the three-survival rate, fixed-effects OR=2.27, 95%
      CI 1.57-3.27, P<0.0001) compared with RFA alone. There was no difference in terms
      of major complications (fixed-effects OR=1.26, 95% CI 0.33-4.77, P=0.73).
      Subgroup analyses by tumor size showed that RFA plus TACE significantly improved
      the survival rates at 1, 3, and 5 years compared with RFA alone in patients with
      HCC larger than 3 cm; however, there was no advantage of TACE plus RFA over RFA
      alone for patients with HCC smaller than 3 cm. The quality of evidence was high
      for the 1-year survival rate, the 3-year survival rate, and major complications.
      No evidence of publication bias was observed. CONCLUSION: High-quality evidence
      suggests that TACE plus RFA improve the survival rates compared with RFA alone
      for patients with HCC larger than 3 cm.

PMID- 23134977
TI  - Expression analysis of calmodulin and calmodulin-like genes from rice, Oryza
      sativa L.
AB  - BACKGROUND: In plants, a large family of calmodulin (CaM) and CaM-like (CML)
      proteins transduce the increase in cytosolic Ca2+ concentrations by binding to
      and altering the activities of target proteins, and thereby affecting the
      physiological responses to a vast array of stimuli. Here, transcript expression
      analysis of Cam and CML gene family members in rice (Oryza sativa L.) was
      extensively examined. RESULTS: Cam and CML genes in rice exhibited differential
      expression patterns in tissues/organs. Under osmotic stress and salt stress,
      expression of OsCam1-1, OsCML4, 5, 8, and 11 was induced with different kinetics
      and magnitude. OsCML4 and 8 mRNA levels significantly increased by 3 h after
      treatment and remained elevated for at least 24 h while expression of OsCam1-1,
      OsCML5 and 11 was up-regulated as early as 1-3 h before rapidly returning to
      normal levels. Several cis-acting elements in response to abiotic stresses,
      including DREs (important promoter elements responsive to drought, high salt, and
      cold stress), were detected in the 5' upstream regions of these genes. The
      observed induction of the GUS activity of transgenic rice plants via the OsCam1-1
      promoter appeared to be biphasic and dependent on the severity of salt stress.
      CONCLUSIONS: Large OsCam and OsCML gene family members likely play differential
      roles as signal transducers in regulating various developmental processes and
      represent important nodes in the signal transduction and transcriptional
      regulation networks in abiotic stresss responses mediated by the complex Ca2+
      signals in plants, which are rich in both spatial and temporal information.

PMID- 23134978
TI  - Loop-loop interactions involved in antisense regulation are processed by the
      endoribonuclease III in Staphylococcus aureus.
AB  - The endoribonuclease III (RNase III) belongs to the enzyme family known to
      process double-stranded RNAs. Staphylococcus aureus RNase III was shown to
      regulate, in concert with the quorum sensing induced RNAIII, the degradation of
      several mRNAs encoding virulence factors and the transcriptional repressor of
      toxins Rot. Two of the mRNA-RNAIII complexes involve fully base paired loop-loop
      interactions with similar sequences that are cleaved by RNase III at a unique
      position. We show here that the sequence of the base pairs within the loop-loop
      interaction is not critical for RNase III cleavage, but that the co-axial
      stacking of three consecutive helices provides an ideal topology for RNase III
      recognition. In contrast, RNase III induces several strong cleavages in a regular
      helix, which carries a sequence similar to the loop-loop interaction. The
      introduction of a bulged loop that interrupts the regular helix restrains the
      number of cleavages. This work shows that S. aureus RNase III is able to bind and
      cleave a variety of RNA-mRNA substrates, and that specific structure elements
      direct the action of RNase III.

PMID- 23134979
TI  - Ingenol mebutate: potential for further development of cancer immunotherapy.
AB  - Ingenol mebutate is a diterpene ester derived from the plant Euphorbia peplus and
      is FDA approved for the topical treatment of actinic keratoses (AK). Shown to be
      efficacious with as little as a 3-day trial, this compound is being further
      tested for the topical treatment of other nonmelanoma skin cancers with promising
      preclinical data. In an effort to elucidate the molecular mechanism of this novel
      drug, Stahlhut et al. (2012) suggest a role for calcium and apoptosis. Further
      studies are needed to evaluate the intracellular mechanisms of ingenol mebutate
      mediated cytotoxicity. Additionally, studies such as this not only shed light on
      the mechanism of ingenol mebutate and its derivatives, but also pave the way for
      evaluating the involvement of the immune system in eliminating drug-treated cells
      and tissues. This has important implications for the development of novel topical
      immune modulatory products and the field of topical immunotherapy.

PMID- 23134980
TI  - Management of severe atopic dermatitis in children.
AB  - Severe childhood atopic dermatitis refers to the presence of recurrent,
      widespread, eczematous dermatitis that significantly interferes with the daily
      activities and/or the quality of life of the affected child and family. The vast
      majority of children with severe, long-standing atopic dermatitis can be managed
      with the appropriate use of topical treatments, including long-term maintenance
      therapy and adjunctive treatments. In the recalcitrant patient, second line
      therapies such as narrowband ultraviolet light therapy and systemic
      immunosuppressants such as cyclosporine, azathioprine, mycophenolate moefetil,
      and methotrexate have been shown to be safe and effective in children with severe
      atopic dermatitis and can lead to sustained clinical improvement. To date,
      biologic therapy has not been uniformly effective in childhood atopic dermatitis.
      Management of severe childhood atopic dermatitis, including topical and
      adjunctive treatments and second-line therapies including systemic
      immunosuppressants will be reviewed here.

PMID- 23134981
TI  - The study of simple chemicals in animals and man: mechanisms of contact
      sensitivity.
AB  - When simple chemical are applied to the skin, a series of events ensues that
      under some conditions ultimately results in contact sensitivity (CS), a proven
      cell-mediated immune response (CMI). Since the discovery of CMI using picryl-Cl
      (PCl) in 1942, we have learned a great deal on the cellular mechanisms involved
      in CS, including the potential to treat warts, skin cancer, autoimmune disorders,
      and allergies. In this review we summarize some of the basic mechanisms of both
      the innate and acquired immune systems involved in CS.

PMID- 23134982
TI  - T helper cell subsets in the development of atopic dermatitis.
AB  - The pathogenesis of atopic dermatitis (AD) requires the orchestration of multiple
      immune cells that mediate inflammation and tissue remodeling in the skin. T
      helper cell subsets that secrete specific cytokines have a central role in
      regulating the inflammatory process. In this review we discuss defined roles for
      T helper subsets in AD, how the microbiome might impact the development and
      function of T helper subsets, and animal models that will be useful for testing
      hypotheses on the interactions of a polarized T-cell response with skin
      inflammation. Future studies that link these areas will provide important insight
      into the development of skin inflammation and AD.

PMID- 23134983
TI  - Ingenol mebutate: induced cell death patterns in normal and cancer epithelial
      cells.
AB  - We investigated the proposed necrotic mechanism of ingenol mebutate, a natural
      compound with anti-cancer properties in human keratinocytes, the human squamous
      cell carcinoma cell line HSC-5, and HeLa cervix carcinoma cells. Topical
      application of a clinical dose of ingenol mebutate 0.05% (1.15 mM) gel to human
      reconstituted full-thickness skin equivalents strongly reduced epidermal, but not
      dermal viability. Ingenol mebutate showed cytotoxic potency between 200-300 M on
      normal and cancer cells. When keratinocytes were induced to differentiate, they
      became significantly less sensitive to ingenol mebutate and half-maximal
      induction of cell death required more than 300 M ingenol mebutate. Cytotoxic
      concentrations of ingenol mebutate caused rupture of the mitochondrial network
      within minutes paralleled by cytosolic calcium release in all cells.
      Subsequently, plasma membrane integrity was lost as seen by propidium uptake into
      the cells. This was in sharp contrast to lysis of cells with low concentrations
      of the detergent Triton X-100 that permeabilized the plasma membrane within
      minutes without affecting organelle morphology. Buffering of intracellular
      calcium and inhibition of the mitochondrial permeability transition pore reduced
      the cytotoxic effect of ingenol mebutate in cancer cells, but not in normal
      keratinocytes. However, these inhibitors could not prevent cell death subsequent
      to prolonged incubation. Our findings reveal that ingenol mebutate does not
      mediate cytotoxicity by a simple lytic, necrotic mechanism, but activates
      distinct processes involving multiple cell organelles in a cell-type and
      differentiation-dependent manner. These data improve our understanding of ingenol
      mebutate-target cell interactions and offer new insights relevant to the removal
      of aberrant cells in human skin.

PMID- 23134984
TI  - The treatment of inflammatory facial dermatoses with topical corticosteroids:
      focus on clocortolone pivalate 0.1% cream.
AB  - OBJECTIVE: Study results evaluating the efficacy and safety of clocortolone
      pivalate 0.1% cream in the treatment of adults, young children, and infants with
      inflammatory facial dermatoses are reported in this article. Clocortolone
      pivalate 0.1% cream, indicated for the relief of the inflammatory and pruritic
      manifestations of corticosteroid-responsive dermatoses, is a mid-potency topical
      corticosteroid (Class 4) that has been studied and used extensively to treat a
      variety of corticosteroid-responsive inflammatory dermatoses, many of which often
      involve facial skin in both adults and children. METHODS: Clocortolone pivalate
      0.01% cream was applied to affected facial skin in subjects presenting with
      seborrheic dermatitis, contact dermatitis, atopic dermatitis, or psoriasis.
      Application was completed three times daily for 21 days. Assessments of erythema,
      edema, transudation, lichenification, scaling, pruritus and/or pain were
      completed at baseline and Days 4, 7, 14, and 21. Overall therapeutic response was
      assessed at all follow-up visits. Forty-nine subjects were entered, ranging in
      age from 1 month to 88 years of age. Thirty-eight subjects completed the studies,
      with 11 subjects lost to follow-up after the first visit. Individuals between the
      ages of 13 and 19 years were pre-emptively excluded to avoid potential
      application of a corticosteroid to acne-affected or acne-prone skin. RESULTS:
      Treatment with clocortolone pivalate 0.1% cream resulted in decreases in
      erythema, edema, transudation, lichenification, scaling, and pruritus/pain in 76%
      of treated study subjects. The overall therapeutic response in approximately two
      thirds of the subjects (68%) was rated as good to excellent. There were 7 adverse
      events noted over the course of the study that were judged to be related to
      treatment, all of which were cutaneous and localized to the site of application
      (acneiform eruptions, burning, and folliculitis). CONCLUSION: Clocortolone
      pivalate 0.1% cream was effective in relieving the signs and symptoms of
      corticosteroid-responsive inflammatory dermatoses involving facial skin,
      including seborrheic dermatitis, contact dermatitis, atopic dermatitis, and
      psoriasis. Overall, the safety profile was favorable and devoid of any treatment
      related serious adverse events.

PMID- 23134985
TI  - Is it time to re-evaluate the treatment of pemphigus?
AB  - Pemphigus vulgaris, foliaceous, and vegetans are potentially fatal, autoimmune,
      vesiculobullous mucocutaneous diseases. In order to prevent potentially fatal
      infection and other complications, most patients with pemphigus require treatment
      with systemic corticosteroids and immunosuppressive agents, although these
      medications often cause chronic and serious adverse effects. Many case reports
      and several trials have documented remissions and clinical improvement in cases
      of pemphigus recalcitrant to standard therapy, who were treated with either
      intravenous immunoglobulin (IVIG) or rituximab, alone or in combination with each
      other. Collectively, the body of evidence from these reports is large enough to
      spark consideration of these treatments early in the management of pemphigus.
      Among the potential benefits of a therapeutic strategy that includes these
      biologic agents are more rapid induction of remission, prevention of
      corticosteroid-related adverse effects, and decreased cost of therapy.
      Considering the outcomes from recent trials with these novel therapies,
      reevaluation of the best-practice treatment of pemphigus seems prudent and
      timely.

PMID- 23134986
TI  - PSOLAR: design, utility, and preliminary results of a prospective, international,
      disease-based registry of patients with psoriasis who are receiving, or are
      candidates for, conventional systemic treatments or biologic agents.
AB  - BACKGROUND: Long-term observational studies can better characterize the impact of
      systemic agents on psoriasis. OBJECTIVE: To describe the on-going Psoriasis
      Longitudinal Assessment and Registry (PSOLAR) study. METHODS: PSOLAR is a large,
      international, long-term, prospective, disease-based registry enrolling patients
      with psoriasis who are receiving, or are candidates for, treatment with systemic
      therapies. The registry fulfills postmarketing regulatory commitments and charges
      a global Steering Committee to manage epidemiological research on psoriasis and
      its therapies. Key demographics, disease characteristics, and medication history
      are collected at enrollment. Adverse events and efficacy data are collected
      longitudinally. RESULTS: The August 2011 annual database extract includes 9,495
      patients enrolled at 266 global centers. At entry, mean percent of body surface
      area affected by psoriasis was 12.3% (peak, 29.5%). Approximately 80% of patients
      were overweight/obese, more than one-third had cardiovascular disease (38.8%) or
      psoriatic arthritis as captured by the treatment center (37.1%), and over half
      had received one or two biologic agents (58.8%) or phototherapy (54.8%). Mean
      duration of participation is 1.3 years, and annual withdrawal rates are less than
      6.5%. Of 9,495 patients, 7,476 have been exposed to at least one biologic agent.
      Serious infections, malignancies, all-cause mortality, and major adverse
      cardiovascular events (ie, myocardial infarction, stroke, cardiovascular death)
      occurred at rates of 1.40, 0.61, 0.37, and 0.36 per 100 patient-years of follow
      up, respectively. LIMITATIONS: PSOLAR may be subject to limitations common to
      observational studies (eg, participation bias and potential confounders).
      CONCLUSION: PSOLAR is a disease-based registry designed to assess therapeutic
      risk and benefit in the general psoriasis population.

PMID- 23134987
TI  - Effectiveness and safety of once-daily doxycycline capsules as monotherapy in
      patients with rosacea: an analysis by Fitzpatrick skin type.
AB  - Rosacea is often under-recognized or misdiagnosed in patients with skin of color
      (Fitzpatrick Skin Types [FST] IV-VI). Subtle clinical features and a low index of
      suspicion likely contribute to less frequent diagnosis in this population.
      Clinical trials of therapeutic agents for rosacea generally include few patients
      from nonwhite racial/ethnic groups and therefore, potential differences in
      treatment outcomes have not been previously studied. The objective of this
      prospective analysis was to fill the gap in knowledge of the effectiveness and
      safety of treatment for rosacea in patients with skin of color. We analyzed data
      from 826 adults aged >= 18 years with papulopustular (subtype 2) rosacea (663 FST
      I-III; 163 FST IV-VI). All patients received doxycycline 40 mg capsules (30 mg
      immediate release and 10 mg delayed release beads) once daily as monotherapy for
      12 weeks in this open-label, multicenter, community-based study. Investigators
      assessed disease severity with the Investigator's Global Assessment (IGA) and
      erythema with the Clinician's Erythema Assessment (CEA). Significant improvement
      in disease severity and erythema was obtained in patients with FST I-III and IV
      VI at week 12 (P<.001). Treatment success, defined as an IGA score of 0 or 1 was
      achieved in 74.6% and 74.3% of patients with FST I-III and IV-VI, respectively.
      Approximately 12% of patients experienced adverse events with no difference
      between the two skin type groups. The results of this prospective subgroup
      analysis of data from a large community-based trial suggest that doxycycline
      produced similar effectiveness and safety profiles in patients with FST I-III and
      IV-VI.

PMID- 23134988
TI  - Apremilast for discoid lupus erythematosus: results of a phase 2, open-label,
      single-arm, pilot study.
AB  - BACKGROUND: Discoid lupus erythematosus (DLE) is a chronic inflammatory disorder
      mediated by Th1 cells. Apremilast is a novel oral PDE4 enzyme inhibitor capable
      of blocking leukocyte production of IL-12, IL-23, TNF-a, INF- with subsequent
      suppression of Th1 and Th17-mediated immune responses, and proven clinical
      efficacy for psoriasis as well as rheumatoid and psoriatic arthritis.
      OBSERVATIONS: Cutaneous Lupus Erythematosus Disease Area and Severity Index
      (CLASI) showed a significant (P<0.05) decrease after 85 days of treatment with
      apremilast 20 mg twice daily in 8 patients with active discoid lupus. The adverse
      events related to the drug were mild and transient. CONCLUSIONS: This is the
      first open label study to use apremilast as a treatment modality for discoid
      lupus. Our observations indicate that apremilast may constitute a safe and
      effective therapeutic option for DLE.

PMID- 23134989
TI  - Adjunctive trichloroacetic acid therapy enhances squaric acid response to verruca
      vulgaris.
AB  - Squaric acid dibutyl ester (SADBE) is a commonly used treatment for verruca
      vulgaris of childhood. Few studies, however, have examined the role of SADBE in
      combination with other topical therapies for warts. We sought to determine if
      trichloroacetic acid 50% (TCA) and/or cantharidin 0.7% improve therapeutic
      response to SADBE. A retrospective chart review of 74 patients who were treated
      for warts at a pediatric dermatology practice in 2010 was performed. Cox
      regression analysis was used to identify determinants of 100% response to SADBE
      and found that number of warts was most important (P=0.002). Trichloroacetic acid
      + SADBE resulted in 100% clearance of warts in all subjects with the shortest
      time-to-clearance (hazard ratio [HR]: 2.45, 95% confidence interval [CI]: 1.14
      5.25, P=0.02). In contrast, addition of cantharidin did not improve response to
      SADBE (HR: 1.13, 95% CI: 0.60-2.13, P=0.59) or TCA + SADBE (HR: 1.16, 95% CI:
      0.65-2.07, P=0.61). These results suggest that combination treatment with TCA 50%
      and SADBE significantly improves the consistency and speed of SADBE-induced
      clearance of warts.

PMID- 23134990
TI  - Pseudoepitheliomatous hyperplasia and transepidermal elimination in lepromatous
      leprosy: does T-cell plasticity play a role?
AB  - BACKGROUND: The longstanding concept of a Th1-Th2 dichotomy in leprosy, with Th1
      predominant tuberculoid leprosy and Th2-predominant lepromatous leprosy (LL), has
      recently been challenged, and Cbl-b overexpression may emerge as an important
      factor in anergy and progression of LL. Moreover, Th17 and Th22 subsets have been
      identified as Th1-Th2 modulators in inflammatory skin diseases, most notably
      psoriasis, but their roles in leprosy have not yet been elucidated. The
      occurrence of pseudoepitheliomatous hyperplasia (PEH) with transepidermal
      elimination of mycobacteria in LL patients, which could theoretically be a portal
      for contact transmission, thus raises important immunological questions: Do Th17
      and/or Th22 subsets mediate epidermal proliferation akin to Th1-driven psoriasis
      in supposedly Th2-predominant LL disease, and is the Th1-Th2 immunostat set
      systemically or locally? Furthermore, which microRNAs (miRs), signal transducers,
      and activators of transcription (STAT) proteins regulate this transition in
      leprosy, if any, and does differential Cb1-b expression play a role? OBSERVATION:
      A 71-year-old man presented with an infiltrative dermopathy characteristic of LL,
      as well as several hyperkeratotic plaques. Microscopic examination of the
      hyperkeratotic lesions demonstrated PEH with loss of the grenz zone and
      transepidermal elimination of acid-fast bacilli, whereas classic histopathologic
      features of LL were present at other sites. HYPOTHESES: We hypothesize that: Th17
      and Th22 T-cell subsets act locally to induce T-cell plasticity in LL lesions,
      manifesting PEH; miR-181a is normal or increased in LL lesions with PEH compared
      to its expressional loss in classic LL lesions; miR-21 and STAT3 are increased in
      LL lesions with PEH, given their association with epithelial hyperproliferation;
      and Cbl-b is diminished in LL lesions with PEH compared to classic LL lesions.
      CONCLUSION: By understanding the factors that regulate T-cell and cytokine
      responses in leprosy, it should be possible to recognize these dynamic
      immunologic processes clinically and histopathologically and devise specific
      immunologic interventions.

PMID- 23134993
TI  - Treatment of severe psoriasis with ustekinumab during pregnancy.
AB  - We present the case of a female, aged 22 years, with a long history of
      recalcitrant pustular psoriasis and psoriatic arthritis, treated with ustekinumab
      during pregnancy. The result of treatment was an uncomplicated pregnancy with
      delivery, at term, of a healthy boy. To our knowledge, this is the first reported
      use of ustekinumab in a human during pregnancy. Following a description of the
      case, we discuss the characteristics of ustekinumab and review the known
      information from human case reports, case series, and animal studies regarding
      the use of TNF-a inhibitors and ustekinumab during pregnancy. We also provide a
      short discussion of administration of ustekinumab during the time period when a
      mother is nursing and the potential for complications to infants in this setting.

PMID- 23134994
TI  - Extramedullary plasmacytomas presenting as asymptomatic nodules on the buttocks
      and thighs.

PMID- 23134995
TI  - DeoxyArbutin and its derivatives inhibit tyrosinase activity and melanin
      synthesis without inducing reactive oxygen species or apoptosis.
AB  - Safety is a major concern in developing commercial skin-lightening agents. Here,
      we report the modulating effects of deoxyArbutin (dA) and its second-generation
      derivatives - deoxyFuran (dF), 2-fluorodeoxyArbutin (fdA), and thiodeoxyArbutin
      (tdA) - on tyrosinase, and consequently, on melanization. Results demonstrate
      that dA and its derivatives inhibit tyrosine hydroxylase and dopa oxidase
      activity of tyrosinase. The inhibition is dose-dependent, thereby inhibiting
      melanin synthesis in intact melanocytes, when used at concentrations that retain
      95% viability of the treated cells in culture. Herein we demonstrate that dA, and
      its second-generation derivatives dF, fdA, and tdA, exhibit dose-dependent
      reductions in melanocyte cell number, primarily due to inhibition of
      proliferation rather than initiation of apoptosis as exemplified by hydroquinone
      (HQ), ie, cytostatic as opposed to cytotoxic. Human and murine melanocytes with
      functional mutations in either tyrosinase or tyrosinase-related protein 1 (Tyrp1)
      are less sensitive to the cytostatic effects of dA and its derivatives. Minimal
      amounts of reactive oxygen species (ROS) were generated upon treatment with dA
      and its derivatives, in contrast to a dramatic amount of ROS induced by HQ. This
      increase in ROS subsequently induced the expression of the endogenous antioxidant
      catalase in treated melanocytes. Treatment with exogenous antioxidants provided
      protection for melanocytes treated with HQ, but not dA and its derivatives,
      suggesting that HQ exerts more oxidative stress. These studies demonstrate that
      dA and its derivatives are relatively safe tyrosinase inhibitors for skin
      lightening or for ameliorating hyperpigmented lesions.

PMID- 23134996
TI  - Enfuvirtide and cutaneous injection-site reactions.
AB  - Enfuvirtide belongs to a newer class of antiretroviral (ARV) agents called fusion
      inhibitors for the treatment of human immunodeficiency virus type 1 (HIV-1)
      infection. Enfuvirtide blocks attachment, binding, and entry of the viral capsid
      into the host CD4+ cell. Administration is only available subcutaneously in a
      twice-daily regimen particularly for those patients who have previously failed
      more than one ARV regimen. Common side effects of enfuvirtide administration
      include fatigue, insomnia, nausea, and diarrhea; however, injection-site
      reactions are the most common side effect and present in nearly all individuals
      undergoing treatment. The spectrum of cutaneous manifestations ranges from little
      to no reaction to cysts, nodules, induration, or sclerodermalike lesions. These
      reactions are mostly variants of iatrogenically induced hypersensitivity and are
      self-limited.

PMID- 23134997
TI  - Virtually painless local anesthesia: diluted lidocaine proves to be superior to
      buffered lidocaine for subcutaneous infiltration.
AB  - BACKGROUND: Many physicians believe that buffering local anesthetics with sodium
      bicarbonate is the best technique for reducing the pain and discomfort associated
      with subcutaneous infiltration. OBJECTIVE: To compare the level of pain and
      discomfort associated with subcutaneous infiltration of lidocaine diluted with
      normal saline to that associated with traditionally buffered lidocaine.
      PATIENTS/METHODS: In a prospective, double-blind trial, 31 patients were asked to
      use a visual analog scale to rank the level of pain and discomfort caused by two
      different solutions of lidocaine with epinephrine. Solution A: 3 mL of 1%
      lidocaine + epinephrine in 30 mL of bacteriostatic 0.9% sodium chloride in a 1:10
      ratio, in which each mL contained 9 mg of sodium chloride and 9 mg of benzyl
      alcohol. Solution B: 5 mL of 8.4% sodium bicarbonate solution and 50 mL of 1%
      lidocaine + epinephrine in a 1:10 ratio. RESULTS: Twenty-eight out of 31 patients
      reported that the solution of lidocaine diluted with normal saline was the least
      painful upon injection. CONCLUSION: Pain and discomfort during subcutaneous
      injection of lidocaine can be reduced by diluting the anesthetic with normal
      saline in a 1:10 ratio.

PMID- 23134998
TI  - Cutaneous reactions to proton pump inhibitors: a case-control study.
AB  - BACKGROUND: Even though proton pump inhibitors (PPIs) are commonly used in
      clinical practice, a limited number of studies are available about cutaneous
      adverse reactions from PPIs, and most of these are case reports. OBJECTIVE: To
      demonstrate the pattern of cutaneous reactions related to PPI usage and to
      evaluate the risk of developing PPI drug eruptions among adult patients. METHODS:
      We reviewed the spontaneous reports of any adverse events associated with PPI
      use, as reported from January 2005 through May 2010 to the Adverse Drug Reaction
      Center at Siriraj Hospital in Thailand. Each control was sampled from 15 patients
      who had consecutive hospital numbers from each study case. RESULTS: The
      prevalence of cutaneous reactions to PPIs varied, ranging from three to 20 per
      100,000 of the treated population. Sixty-four patients with a history of reaction
      to PPIs, and 65 controls were enrolled. Most cutaneous reactions were attributed
      to omeprazole (n=50; 78.1%), and the most frequently observed cutaneous reaction
      was maculopapular rash (43.8%). None of the patients experienced a cross-reaction
      between individual PPIs. CONCLUSION: Cutaneous adverse reactions to PPIs range
      from minor drug rashes to a severe, life-threatening reaction. Individuals with a
      history of adverse drug reaction have an increased risk of cutaneous reaction to
      PPIs.

PMID- 23134999
TI  - Regional variations in percutaneous absorption.
AB  - BACKGROUND: In its simplest definition, percutaneous absorption (PA) is the
      amount of substance that passes through the stratum corneum compared with the
      amount applied. The study of the PA of substances is relevant to the fields of
      dermatopharmacology and occupational medicine. The quantity and rate in which a
      given chemical absorbs through the skin depend on a multitude of variables. One
      obvious determinant of PA is the application site. This overview summarizes
      currently available data on the topic of regional variations in PA and possibly
      suggests a direction for future research efforts. METHODS: Searches were
      performed in Medline and EMBASE. Extensive bibliographical research was performed
      in order to identify additional relevant data sets using Web of Science. Results
      were screened for inclusion of more than one anatomical site, the use of
      validated methods, and the use of human subjects. RESULTS: We identified eight
      relevant studies, from which we present data. CONCLUSION: Determining regional
      variations in PA is a complex yet critically important task. Current data sets
      are scarce and inadequate for drawing complete conclusions, but the data seem to
      suggest increased PA in the forehead and genital skin compared with other
      anatomical regions. It is our hope that, with the advent of new technologies, an
      anatomical PA map will begin to emerge from the data. Such descriptive
      understanding will guide investigation into the mechanisms involved in
      determining anatomical site differences in PA.

PMID- 23135000
TI  - The effect of combined calcipotriol and betamethasone dipropionate ointment in
      the treatment of vitiligo: an open, uncontrolled trial.
AB  - BACKGROUND: Vitiligo is a frequent dyschromia characterized by achromic macules
      that reflect the absence of melanocytes. It affects 1% of the general population.
      Treatment of vitiligo is a challenge. Recently, topical calcipotriol has been
      claimed to be effective, either as monotherapy or as part of combination
      therapies. OBJECTIVE: To evaluate the efficacy and safety of calcipotriol
      0.005%/betamethasone dipropionate 0.05% ointment in the treatment of vitiligo.
      METHODS: Thirty-one patients with vitiligo were enrolled in our study. The mean
      age of the patients was 32.6 + 11 years (range 18-56 years) and the mean duration
      of vitiligo was 3.7 + 5.8 years (range 0.07-30 years). Patients were treated with
      topical calcipotriol 0.005%/betamethasone dipropionate 0.05% ointment twice a day
      for at least 12 weeks, and the degree of repigmentation was analyzed using
      digital photography at baseline and at weeks 4, 8, and 12. The response was
      evaluated as excellent (76%-100%), moderate (51%-75%), mild (26%-50%), minimal
      (1%-25%), or no response. Possible adverse effects during the treatment period
      were also noted. RESULTS: Three patients (9.7%) had an excellent response, six
      patients (19.4%) had a moderate response, eight patients (25.8%) had a mild
      response, seven patients (22.6%) had a minimal response, and seven patients
      (22.6%) had no response. Patients at a progressive phase responded better to this
      ointment than patients at a stable phase (P=.005). The correlations between
      response rate and the duration of the disease were not significant (P=.791). Four
      adverse events related to the ointment were reported (pruritus, n=2; acne, n=2).
      CONCLUSION: Calcipotriene 0.005%/betamethasone dipropionate 0.05% ointment is
      effective and well tolerated in the treatment of patients with vitiligo.

PMID- 23135001
TI  - Nutritional stress affects an atypical cap-binding protein in Leishmania.
AB  - Many eukaryotes encode multiple isoforms of the cap-binding translation
      initiation factor (eIF4E). Leishmanias and other trypanosomatids encode four
      paralogs of this protein, but none can complement the eIF4E function in a yeast
      mutant. A low conservation is observed between the four paralogs, suggesting they
      assist these organisms survive a multitude of conditions encountered throughout
      the life cycle. Earlier attempts to decipher their function led to identification
      of LeishIF4E-4 as the canonical translation initiation factor. LeishIF4E-1
      appears to function during thermal stress, via a mechanism not yet understood.
      LeishIF4E-3 hardly binds cap-4 and is, therefore, less likely to serve as a
      typical initiation factor. Although it interacts with an eIF4G homolog, LeishIF4G
      4, the two polypeptides do not co-migrate on sucrose gradients. While LeishIF4E-3
      enters large particles that increase in size during nutritional stress, LeishIF4G
      4 is found only in the top fractions. Confocal microscopy localized LeishIF4E-3
      (but not LeishIF4G-4) within nutritional stress-induced granules. Accordingly,
      interaction between the two proteins reduced upon starvation. We therefore
      propose that under normal conditions, LeishIF4G-4 sequesters LeishIF4E-3 in the
      cytoplasm. During a nutritional stress, LeishIF4E-3 is modified and released from
      LeishIF4G-4 to enter stress granules, where inactive mRNAs are stored. Binding of
      LeishIF4G-4 to LeishIF4E-3 requires a short peptide within the LeishIF4G-4 N
      terminus, which bears no similarity to the consensus 4E-binding peptide,
      YXXXXLPhi. Mutational analysis combined with structure prediction indicates that
      this interaction is based on an obligatory, conserved alpha helix in LeishIF4G-4.
      These features further highlight the uniqueness of LeishIF4E-3 and how it
      interacts with its binding partners.

PMID- 23135002
TI  - Telomeres at a glance.

PMID- 23135003
TI  - Controlled synthesis of novel Au@MIL-100(Fe) core-shell nanoparticles with
      enhanced catalytic performance.
AB  - A novel porous Au@MIL-100(Fe) core-shell nanocatalyst with controllable MIL
      100(Fe) shell thickness has been fabricated by using a versatile step-by-step
      fashion. Catalytic studies show that the Au@MIL-100(Fe) nanocatalyst exhibits
      much higher catalytic activity than the pure Au nanoparticles, suggesting that
      the MIL-100(Fe) shell enhances the catalytic activity via a synergistic effect.

PMID- 23135004
TI  - Asymmetric siRNA targeting the bcl-2 gene inhibits the proliferation of cancer
      cells in vitro and in vivo.
AB  - Small interfering RNAs (siRNAs) are valuable reagents for efficient gene
      silencing in a sequence-specific manner via the RNA interference (RNAi) pathway.
      The current synthetic siRNA structure consists of symmetrical duplexes of 19-21
      base pairs (bp) with 2 nucleotide (nt) 3' overhangs. In this study, we report
      that an asymmetric siRNA (asiRNA) consisting of 17 bp duplex region (17 bp
      asiRNA) exhibited potent activity in inhibiting bcl-2 gene expression and cancer
      cell proliferation in vitro. Importantly, this asiRNA structure significantly
      reduced off-target silencing by the sense strand. To improve the stability of the
      17 bp asiRNA, we synthesized a series of chemically modified 17 bp asiRNAs.
      Further experiments showed that in comparison with the 17 bp asiRNA, the 17 bp
      asiRNA-M2, one of the modified 17 bp asiRNAs, exhibited a comparable gene
      silencing activity and an improved stability in vitro. Furthermore, the 17 bp
      asiRNA-M2 with a proteolipid micelle delivery system can effectively suppress the
      growth of H22 and BGC 803 tumors in vivo. These results suggest that the
      chemically modified asiRNAs may have potential as an effective therapeutic
      approach for cancer gene therapy in the future.

PMID- 23135005
TI  - Combination and monotherapy of Leishmania major infection in BALB/c mice using
      plant extracts and herbicides.
AB  - BACKGROUND & OBJECTIVES: Leishmaniasis is a growing health problem in many parts
      of the world. Efforts to find new chemotherapeutics for leishmaniasis remain a
      priority. This study was carried out to determine the effect of combination and
      monotherapies using plant extracts and herbicides on Leishmania major infection
      in BALB/c mice. METHODS: The herbicides and saponin extract were purchased from
      Sigma. Roots of Plumbago capensis were collected from Karura forest, Nairobi,
      Kenya. Plant extractions were done in KEMRI at Center for Traditional Medicines
      and Drugs Research. RESULTS: Lesion sizes after infection of BALB/c mice were
      similar in all the experimental groups till the onset of therapeutic treatments
      (p >0.05). At 15 days post-treatment, significant differences (p < 0.05) were
      discerned in the lesion sizes of the BALB/c mice in all the mono- and combined
      treated groups. However, the combined therapies caused total elimination of the
      parasites from the lesions and significantly reduced parasite burden in liver and
      spleen compared to the untreated controls at the end of the experiment.
      INTERPRETATION & CONCLUSION: The results of this study demonstrate that
      combination therapy using alternative administration of saponin, acriflavine,
      trifluralin and plumbagin is effective in treating L. major infection in mice. In
      this regard, an investigation into the efficacy of these combined therapies
      against other Leishmania strains should be explored further. Furthermore, studies
      with these combination therapies should be done on non-human primates such as the
      vervet monkey (Cercopithecus aethiops).

PMID- 23135006
TI  - Substandard artemisinin-based antimalarial medicines in licensed retail
      pharmaceutical outlets in Ghana.
AB  - BACKGROUND & OBJECTIVES: The artemisinin-based antimalarial medicines are first
      line medicines in the treatment of severe and uncomplicated falciparum malaria.
      Numerous brands of these medicines manufactured in various countries are
      available in the Ghanaian market. The study was aimed at evaluating the
      authenticity and quality of selected brands of artemisinin-based antimalarial
      medicines marketed in Ghana. METHODS: In all, 14 artemisinin-based antimalarial
      medicines were purchased from pharmacies (P) and licensed chemical shops (LCSs)
      in the Kumasi metropolis, Ghana. Simple field tests based on colorimetry and thin
      layer chromatography were employed in determining the authenticity of the
      samples. Important quality assessment tests, namely uniformity of mass, crushing
      strength, disintegration time, and the percentage content of active
      pharmaceutical ingredients (APIs) were determined. RESULTS: All the brands tested
      contained the stipulated APIs. Artesunate tablet AT2 failed the uniformity of
      mass test while artesunate tablets AT3 & AT4 as well as amodiaquine tablets AM4 &
      AM6 failed the crushing strength test. All the six artemether-lumefantrine tablet
      brands passed the uniformity of mass, crushing strength and disintegration tests.
      Only artemether-lumefantrine tablet brand AL1 contained the correct amount of the
      drugs. The other 13 artemisinin products contained either a lower (underdose) or
      higher (overdose) amount of the specified drug. Artesunate monotherapy tablets
      were readily available in pharmacies and licensed chemical shops. INTERPRETATION
      & CONCLUSION: All the artemisinin-based medicines tested (except AL1) were of
      substandard quality. The results demonstrate the need for continuous monitoring
      and evaluation of the quality of artemisininbased antimalarials in the Ghanaian
      market. Also, the practice of artemisinin antimalarial monotherapy is prevalent
      in Ghana. Determined efforts should, therefore, be made to eradicate the practice
      to prevent the development of resistance to the artemisinins.

PMID- 23135007
TI  - Biting on human body parts of Simulium vectors and its implication for the
      manifestation of Onchocerca nodules along Osun River, southwestern Nigeria.
AB  - BACKGROUND: The biting preference of Simulium vectors has been known to influence
      the distribution of Onchocerca nodules and microfilariae in human body. There is,
      however, variation in biting pattern of Simulium flies in different geographical
      locations. This study investigates the biting pattern on human parts by Simulium
      vectors along Osun river system where Simulium soubrense Beffa form has been
      implicated as the dominant vector and its possible implication on the
      distribution of Onchocerca nodules on human body along the river. METHODS: Flies
      were collected by consented fly capturers on exposed human parts namely head/neck
      region, arms, upper limb and lower limb in Osun Eleja and Osun Budepo along Osun
      river in the wet season (August-September) and the dry season (November-December)
      in 2008. The residents of the communities were also screened for palpable
      Onchocerca nodules. RESULTS: The results showed that number of flies collected
      below the ankle region was significantly higher than the number collected on
      other exposed parts (p <0.05) while the least was collected on head/neck region
      in both seasons. The lower trunk was the most common site (60%) for nodule
      location at Osun Eleja followed by upper trunk (40%). Nodules were not found in
      the head and limb regions. At Osun Budepo, the upper trunk was the most common
      site of the nodule location (53.8%) followed by the lower trunk (38.5%) and head
      region (7.7%). CONCLUSION: Though, most of the flies were caught at the ankle
      region, the biting of other parts coupled with the presence of nodules at the
      head and upper trunk regions showed that Simulium vectors could obtain
      microfilariae from any part of the body, thus increasing the risk of
      onchocerciasis transmission.

PMID- 23135008
TI  - Effect of ivermectin on Trypanosoma brucei brucei in experimentally infected
      mice.
AB  - BACKGROUND & OBJECTIVES: Human and livestock African trypanosomiasis, otherwise
      known as sleeping sickness, is a neglected tropical disease of public health
      importance in west and central Africa. In view of the adverse side effects of the
      antitrypanosomal drugs, the relatively few side effects observed in ivermectin
      use, and because both onchocerciasis and typanosomiasis occur in overlapping foci
      in Africa, it would be desirable if the ivermectin that has been used
      successfully on onchocerciasis management could also be used in the control and
      treatment of trypanosomiasis. METHOD: In this study, prophylactic and therapeutic
      effects of ivermectin (Mectizan) were investigated in albino mice infected with a
      Nigerian strain of Trypanosoma brucei brucei. RESULTS: A 300 MUg/ml/kg dose had
      the most effective impact because it showed the highest mean survival time of 12
      days in both the treatment and prophylactic groups of mice. This dose also
      enhanced the defence capacity of the treated groups. It also had positive
      influence on the packed cell volume (PCV) and the state of anaemia in the
      trypanosome infected mice, hence, improving their survivability. INTERPRETATION &
      CONCLUSIONS: Our report indicates that using the 300 MUg/ml/kg dose of ivermectin
      increases the mean survival period from 5 to 12 days. This suggests that
      ivermectin could be possibly used in the treatment of trypanosomiasis. Further
      studies will be required to show whether proper treatment may entail a single
      dose, as used in this study; an increased number of doses, or combinations with
      other drugs.

PMID- 23135009
TI  - Evaluation of host humoral antibody production against Plasmodium falciparum
      recombinant circumsporozoite antigen in Nigerian children.
AB  - BACKGROUND & OBJECTIVES: The challenge of malaria and efforts targeted at
      developing malaria vaccines triggered this study on the reactivity of IgG and its
      subclasses in the test serum specific to CSP. This work was directed at assessing
      the influence of age and gender on host humoral antibody against Plasmodium
      falciparum recombinant circumsporozoite antigen in Nigerian children. METHODS: In
      all, 67 serum samples (>10,000 parasites/MUl of blood) collected from malaria
      infected children at the University College Hospital, Ibadan during the
      transmission season were analyzed by ELISA. RESULTS: The mean absorbance values
      of IgG subclasses reactive against P. falciparum CSP appeared to be age-dependent
      and ranged from 0.01 for IgG4 in younger children to 0.95 for IgG3 in older
      children. The sixty-seven subjects investigated in this study had significantly
      higher mean IgG1 and IgG3 than the uninfected controls (p <0.01). This follows
      the order IgG3>IgG1>IgG2>IgG4 which confirmed the prevalence of the cytophilic
      antibodies (IgG1 and IgG3) in 65% of the malaria infected children over the non
      cytophilic subclasses (IgG2 and IgG4). Similarly, there was low production of
      IgG4 and IgG2 levels in 35% of the subjects compared with control. IgG was
      detected in the serum of North American Subjects (NAS) which served as negative
      control for CSP-specific IgG subclasses. Although the NAS titre was lower than
      that of the malaria subjects in Nigeria, its IgG2 was, however, higher (0.16)
      than that of other subclasses. The mean absorbance values of total serum IgG
      subclass were higher than those of IgG subclasses specific to P. falciparum
      circumsporozoite antigen. The mean absorbance values of the total serum IgG
      subclass follows the order IgG2>IgG1>IgG4>IgG3. INTERPRETATION & CONCLUSION: Age
      and gender-dependent correlations of results suggest that acquired immunity could
      play a significant role in protection from malaria. Antibody levels are higher in
      male than female children of the same age group. Antibody levels also increase
      with age in both the male and female children.

PMID- 23135010
TI  - Incidence, management, and reporting of severe and fatal Plasmodium falciparum
      malaria in secondary and tertiary health facilities of Alipurduar, India in 2009.
AB  - BACKGROUND & OBJECTIVES: The proportion of malaria cases that are complicated and
      fatal are not well described in India. Alipurduar sub-division of Jalpaiguri
      district in West Bengal is highly endemic for malaria. We constructed a
      retrospective cohort of severe malaria patients admitted in the secondary and
      tertiary care facilities in Alipurduar to determine the incidence, assess the
      management, and evaluate the reporting of severe and fatal malaria. METHODS: We
      reviewed routine surveillance data and the case records of all the malaria
      patients admitted in all secondary and tertiary care facilities, both public and
      private. We defined severe malaria cases as Plasmodium falciparum infection with
      clinical signs and symptoms of organ involvement in a resident of Alipurduar
      admitted during January to December 2009. We compared clinical and demographic
      characteristics of severe malaria cases that died with those who survived. We
      also reviewed human resources and laboratory facilities available for the
      treatment of severe malaria in these health facilities. RESULTS: During 2009,
      6191 cases of P. falciparum in Alipurduar were reported to the malaria
      surveillance system. We identified 336 (5.4%) cases of severe malaria among which
      33 (9.8%) patients died. Four malaria deaths were also recorded from primary
      health centres. Only 17 of the 37 (46%) total deaths recorded were reported to
      the routine surveillance system. Most severe cases were males (65%), aged >15
      years (72%), and nearly half were admitted to secondary care hospitals (48%). In
      multivariate analysis, the risk factors associated with death included increased
      delay fever onset and hospitalization, treatment in a secondary level hospital,
      younger age, and multi-organ involvement. The secondary level public hospital had
      too few physicians and nurses for supporting severe malaria patients as well as
      inadequate laboratory facilities for monitoring such patients. CONCLUSIONS:
      Severe and fatal malaria continue to burden Alipurduar and record keeping in
      health facilities was poor. Many malaria deaths were not routinely reported even
      in the public sector. Improved surveillance and increased human and laboratory
      resources are needed to reduce malaria mortality.

PMID- 23135011
TI  - Species composition of the Anopheles gambiae complex across eco-vegetational
      zones in Bayelsa State, Niger Delta region, Nigeria.
AB  - BACKGROUND & OBJECTIVES: Correct vector identification is an important task in
      the planning and implementation of malaria vector control programmes. This study
      was designed to provide baseline information on the species composition and
      distribution of members of the Anopheles gambiae complex in three eco
      vegetational zones in Bayelsa state, Nigeria. METHODS: Adult mosquitoes were
      collected by pyrethrum spray catch (PSC) in randomly selected houses during
      September 2009-August 2010. Anopheles mosquitoes were identified using standard
      morphological keys. Mosquitoes identified as An. gambiae s.l. were used for
      species specific PCR-assays. RESULTS: Out of 203 Anopheles gambiae s.l.
      successfully amplified, 180 (88.7%) were Anopheles gambiae s.s., 14 (6.9%) were
      An. melas and 9 (4.4%) were An. arabiensis. The variation in the sibling species
      composition of An. gambiae s.l. was not significant (p >0.05). Anopheles gambiae
      s.s. was predominant in all the collections with three sibling species occurring
      in all the eco-vegetational zones. INTERPRETATION & CONCLUSION: The observation
      of An. melas in the fresh water swamp forest of Yenagoa is of importance in
      malaria epidemiology. These findings are of importance in the planning and
      implementation of malaria vector control strategy in the three eco-vegetational
      zones of Bayelsa state.

PMID- 23135012
TI  - Genetic analysis of clinical isolates of Leishmania major from Isfahan, Iran.
AB  - BACKGROUND & OBJECTIVES: Leishmaniasis is a geographically widespread severe
      disease which includes visceral leishmaniasis (VL) and cutaneous leishmaniasis
      (CL). There are 350 million people at risk in over 80 countries. In the Old
      World, CL is usually caused by Leishmania major, L. tropica, and L. aetiopica
      complex of which 90% of cases occur in Afghanistan, Algeria, Iran, Iraq, Saudi
      Arabia, Syria, Brazil and Peru. Recently, Eslami et al (2011) reported a novel
      TRYP6 gene encoding tryparedoxin peroxidase from an Iranian L. major strain
      exhibiting homology with the related gene in a divergent genus of Kinetoplastida,
      the Crithidia. This prompted us to analyze the mentioned gene in 100 isolates
      obtained from patients with suspected CL. Consequently, we analyzed internal
      transcribed spacer 1 (ITS1) region, RNA polymerase II largest subunit (RPOIILS)
      and the mitochondrial DNA polymerase beta (DPOLB). METHODS: After obtaining
      samples from 100 patients, DNA extraction was performed and TRYP6 was analyzed
      using conventional PCR. All samples harbouring TRYP6 with smaller size (555 bp)
      were analysed based on three other regions: ITS1, RPOIILS and DPOLB genes.
      RESULTS: Results showed that 10% of the isolates have the same character as
      observed in our previous study. The ITS1-RFLP-PCR of this 10% isolates showed
      their similarity to the one from Crithidia fasciculata. RNA polymerase II largest
      subunit (RPOIILS) showed genetic diversity but the mitochondrial DNA polymerase
      beta (DPOLB) did not show any genetic diversity. CONCLUSION: This study might
      also help in solving the problems concerning Leishmaniasis outbreaks currently
      reported in Iran and some other endemic regions of the world.

PMID- 23135013
TI  - Resting behaviour of Anopheles stephensi type form to assess its amenability to
      control malaria through indoor residual spray.
AB  - BACKGROUND & OBJECTIVES: In the present study, an attempt was made to find
      reasons of ineffectiveness of indoor residual spray to interrupt malaria
      transmission by investigating the behaviour of two variants of Anopheles
      stepnesi, viz. type form and mysorensis in rural areas of Rajasthan, India.
      METHODS: Both low malarious (DDT spray from 1958 to 1976) and high malarious (DDT
      spray from 1958 to April 2006) villages were selected for the study in Arid zone
      district Jodhpur, Rajasthan during March-April 2006. Resting behaviour of the
      species during all its movement rhythms covering 24 h period related to: (i)
      swarming/ mating; (ii) pre- and post-biting rest; (iii) after feed resting
      between hoping movements; (iv) night and day time resting and; (v) diel activity
      movements in response to temperature changes, were carried out. RESULTS: The
      results showed that household objects like cupboards, furnitures, hanging
      clothes, goods stacked on loft, stored clothes, cobwebs and floor were the
      dominant resting sites both in sprayed and unsprayed villages. About 95 and 97%
      of An. stephensi preferred to rest on household objects of unsprayed and sprayed
      villages respectively. There was no significant difference in resting behaviour
      of the species in both groups of villages (p >0.05). The pre-biting resting time
      was recorded as 5 to 15 min whereas post-biting resting time lasted for 15 to 25
      min. After biting outdoor (in courtyard--open to sky) species starts entering the
      rooms at around 2330 hrs. It was observed that during III quarter (0100 to 0400
      hrs) maximum species entered into the room were 56% in unsprayed and 62% in
      sprayed villages. Statistically there was no significant difference in the entry
      of mosquitoes (p >0.05) in both the groups of villages. CONCLUSION: Before DDT
      era, An. stephensi was found resting at all heights of the walls inside the human
      dwellings. Present study revealed that An. stephensi is trying to avoid sprayable
      surfaces and tend to rest on unsprayable surfaces during all its movement rhythms
      starting from swarming, pre-/post-biting and during hopping movements in the
      courtyard and thereafter household objects inside the room as final day time
      resting. It was concluded that changed behaviour of resting of An. stephensi on
      unsprayable objects in sprayed rooms largely accounted for failure of malaria
      control. Control of An. stephensi, thus requires an integrated vector control
      strategy based upon interesectoral, environmental, larviciding with
      chemical/biolarvicide and use of larvivorous fish wherever feasible. Such a
      control strategy offers cost-effective and sustainable option than indoor
      residual spray.

PMID- 23135014
TI  - Field evaluation of Icon(r)Life, a long-lasting insecticidal net (LLIN) against
      Anopheles culicifacies and transmission of malaria in District Gautam Budh Nagar
      (Uttar Pradesh), India.
AB  - BACKGROUND & OBJECTIVES: In the present study, Icon(r)Life net, a long-lasting
      polyethylene net, 100 denier and bursting strength of minimum 280 kpa
      incorporated with deltamethrin @ 65 mg/m2 was evaluated for its efficacy in
      reducing the density of malaria vector Anopheles culicifacies and impact on
      malaria prevalence in a malaria endemic area of District Gautam Budh Nagar,
      India. METHODS: Wash resistance of Icon(r)Life LLIN was determined up to 20
      serial washings using An. culicifacies in cone bioassays under field conditions.
      Efficacy of Icon(r)Life LLIN was determined in the field in three sets of
      villages in District Gautam Budh Nagar (Uttar Pradesh), India, selected randomly
      for the intervention with Icon(r)Life LLIN, untreated nets and a control without
      any intervention for the period of August 2008-July 2009. Entomological and
      malariometric indices in all the three villages were compared during pre- and
      post-intervention periods for one year against An. culicifacies. A survey was
      also conducted in the village provided with Icon(r)Life LLIN to assessing the
      perception of community regarding acceptance of these nets by the community.
      RESULTS: In cone bioassays on Icon(r)Life LLIN with An. culicifacies, >95%
      knockdown within 1 h and 100% mortality after 24 h exposure were reported even
      after 20* serial washings under field conditions. Results of the field study
      revealed reduced entry rate, resting density and parity rate of An. culicifacies
      in the village with Icon(r)Life LLIN when compared to no net and untreated net
      villages. Number of malaria cases reported were less in the Icon(r)Life LLIN used
      villages when compared to other two villages. The community compliance and
      acceptance was high and no adverse health events were reported by the households
      using these nets. CONCLUSIONS: Icon(r)Life LLIN is an effective intervention for
      the control of An. culicifacies transmitted malaria in India. Long-term studies
      are indicated for the duration of effectiveness and to ascertain the
      epidemiological impact of the use of Icon(r)Life nets.

PMID- 23135015
TI  - The prevalence of bovine trypanosomes in parts of Benue state, north-central
      Nigeria.

PMID- 23135016
TI  - Platelet count and parasite density: independent variable in Plasmodium vivax
      malaria.

PMID- 23135017
TI  - Bradycardia in a patient with Crimean-Congo hemorrhagic fever related to
      ribavirin treatment.

PMID- 23135018
TI  - Neurological sequelae in pediatric cerebral malaria: the Indian perspective.

PMID- 23135019
TI  - Optic neuritis: a blurry issue.

PMID- 23135020
TI  - Paroxysmal occipital discharges suppressed by eye opening: spectrum of clinical
      and imaging features at a tertiary care center in India.
AB  - BACKGROUND: Paroxysmal occipital discharges (PODs) demonstrating the phenomena of
      fixation-off sensitivity have classically been described in childhood epilepsies
      with occipital paroxysms. AIM: We attempted to delineate the demographic,
      clinical and imaging characteristics of patients whose interictal
      electroencephalograms (EEGs) showed occipital discharges with fixation-off
      sensitivity at our center. MATERIALS AND METHODS: During the period between 2003
      and 2005, patients whose interictal EEGs showed PODs were included in the study.
      A detailed history, clinical examination and EEG findings along with imaging
      characteristics were analyzed. RESULTS: Of the 9,104 interictal EEGs screened
      during the study period, 11 patients (6 females and 5 males) aged between 5 and
      17 years were identified to have PODs with fixation-off sensitivity. Five had
      history of generalized tonic-clonic seizures. Three patients could be classified
      under Panayiotopoulos syndrome; the remaining 8 (72.2%) patients had symptomatic
      epilepsy. CONCLUSION: This study suggests that the phenomenon of fixation-off
      sensitivity is found not only in patients of idiopathic focal epilepsies, but
      also in a substantial number of patients of symptomatic epilepsy. The high
      proportion of symptomatic epilepsy with phenomenon of fixation-off sensitivity
      may be related to the referral pattern.

PMID- 23135021
TI  - Autologous bone marrow-derived stem cells in amyotrophic lateral sclerosis: a
      pilot study.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder
      with no effective treatment. Stem cell therapy may be one of the promising
      treatment options for such patients. AIM: To assess the feasibility, efficacy and
      safety of autologous bone marrow-derived stem cells in patients of ALS. SETTINGS
      AND DESIGN: We conducted an open-label pilot study of autologous bone marrow
      derived stem cells in patients with ALS attending the Neurology Clinic of a
      tertiary care referral centre. MATERIALS AND METHODS: Ten patients with ALS with
      mean revised ALS Functional Rating Scale (ALSFRS-R) score of 30.2 (+/- 10.58) at
      baseline received intrathecal autologous bone marrow-derived stem cells. Primary
      end point was improvement in the ALSFRS-R score at 90, 180, 270 and 365 days post
      therapy. Secondary endpoints included ALSFRS-R subscores, time to 4-point
      deterioration, median survival and reported adverse events. Paired t-test was
      used to compare changes in ALSFRS-R from baseline and Kaplan-Meier analysis was
      used for survival calculations. RESULTS: There was no significant deterioration
      in ALSFRS-R composite score from baseline at one-year follow-up (P=0.090). The
      median survival post procedure was 18.0 months and median time to 4-point
      deterioration was 16.7 months. No significant adverse events were reported.
      CONCLUSION: Autologous bone marrow-derived stem cell therapy is safe and feasible
      in patients of ALS. Short-term follow-up of ALSFRS-R scores suggests a trend
      towards stabilization of disease. However, the benefit needs to be confirmed in
      the long-term follow-up period.

PMID- 23135022
TI  - Optic neuritis: experience from a south Indian demyelinating disease registry.
AB  - BACKGROUND: Natural history of optic neuritis (OPN) has not been studied in
      India. AIM: To study consecutive patients with optic neuritis as the initial
      manifestation of the neurologic disease and with disease duration of 3 or more
      years registered in the Mangalore Demyelinating Disease Registry. MATERIALS AND
      METHODS: The study included 59 patients with a primary diagnosis of optic
      neuritis (confirmed by either an ophthalmologist or a neurologist or both). All
      the patients were investigated and followed-up in the clinic. RESULTS: During the
      follow-up of the 59 patients, 29 (49%) patients developed multiple sclerosis
      (MS); 3 (5%) patients neuromyelitis optica (NMO); and 13 (22%) patients chronic
      relapsing inflammatory optic neuritis (CRION), while the remaining 14 (24%) did
      not either progress or relapse, monophasic OPN. An initial abnormal magnetic
      resonance imaging predicted conversion to MS in all 7 patients who had imaging at
      onset. Patients with NMO were left with significant residual visual loss
      distinguishing NMO from MS. In this large series of patients with CRION, nearly
      50% of patients had deterioration in vision while steroids were being tapered.
      Long-term immunosuppression was essential for maintaining good visual outcome in
      both NMO and CRION. CONCLUSIONS: Optic neuritis in India appears similar to that
      in the West with nearly 50% developing MS in the long term.

PMID- 23135023
TI  - Translation and validation of restless leg syndrome quality of life questionnaire
      in Hindi language.
AB  - BACKGROUND: Restless legs syndrome (RLS) itself as well as the problems that are
      secondary to RLS may worsen the quality of life. AIM: The aim of this study is to
      translate and validate the Restless Legs Syndrome Quality of Life (RLS-QOL)
      questionnaire in Hindi language. SETTINGS AND DESIGNS: Patients attending
      psychiatry OPD and sleep clinic in a tertiary care teaching hospital. MATERIALS
      AND METHODS: Thirty four consecutive patients of RLS and twenty nine control
      subjects were included in the study. Permission for translation and validation of
      RLS-QOL questionnaire scale was obtained. Translation was done according to the
      guidelines provided by the publisher. After translation, the final version of the
      scale was applied in both the groups to find the reliability and validity.
      STATISTICAL ANALYSIS: SPSS, version 17.0 was used for the analysis. Independent
      sample t test was used to compare age. Chi-square test was applied to compare non
      parametric variables. Pearson's and Spearman's correlations were used to find out
      the correlation between parametric and non-parametric items, respectively.
      Reliability analysis was done by using Cronbach's alpha. RESULTS: Among the RLS
      subjects, mean Insomnia Severity Index (ISI) score, International Restless Legs
      Syndrome Severity Rating Scale (IRLS) score and Computed Score of RLS-QOL
      questionnaire were 25.43 (7.39), 12.7 (8.34) and 29.8 (8.39), respectively. A
      statistically significant difference was observed between both the groups on all
      these scores (ISI: t= -11.2, P<0.001, 95% CI= -22.62 to -15.76; IRLS: t = -8.1,
      P< 0.001, 95% CI =-15.81 to -9.58; RLS-QOL: t =-19.07, P<0.001 with 95% CI = 
      32.69,- 28.83). A significant correlation between ISI and RLS-QOL (r2 = 0.59; P<
      0.001) was seen. Most of the items also showed good correlation with each other.
      Internal consistency done by Cronbach's alpha showed good correlation (0.85).
      CONCLUSION: Hindi version of the Restless Legs Syndrome Quality of Life (RLS-QOL)
      questionnaire is a valid and reliable tool for the assessment of the quality of
      life in patients with RLS.

PMID- 23135024
TI  - Status of O6 -methylguanine-DNA methyltransferase [MGMT] gene promoter
      methylation among patients with glioblastomas from India.
AB  - BACKGROUND: O6 -methylguanine DNA methyltransferase [MGMT] gene promoter
      methylation has emerged as a promising marker in determining resistance to
      temozolomide, used in the treatment of patients with glioblastomas. AIM: To
      determine the frequency of MGMT promoter methylation among patients with
      glioblastomas using methylation-specific polymerase chain reaction (MSP) and
      compare it to the results obtained by bisulfite sequencing of a subset of
      samples. MATERIALS AND METHODS: DNA obtained from the frozen tissue of 27 samples
      of glioblastomas and three other gliomas, were analyzed for MGMT promoter
      methylation using a nested MSP assay. Sixteen samples were also subjected to
      bisulfite sequencing to determine the methylation status of 27 CpG sites within
      the sequenced region of the MGMT promoter. Data with respect to radiation,
      chemotherapy and survival outcome was also collected. RESULTS: MGMT promoter
      methylation was seen in 67% of the cases included in the study using frozen
      tissues by MSP analysis, while 62% were methylated among glioblastomas alone.
      There was a 100% concordance between the results obtained by MSP analysis and
      bisulfite sequencing. Clinical outcome was known among 67% of cases and
      methylation was higher among those patients who had no recurrence, though it was
      not statistically significant [P=0.44]. CONCLUSION: The frequency of methylation
      seen in this study concurs with that reported earlier from the country. MSP was
      easy to perform and interpret. However, the utility of this testing system in a
      routine diagnostic setting is still being debated.

PMID- 23135025
TI  - Nuclear expression of beta-catenin and stem cell markers as potential prognostic
      indicators in medulloblastoma.
AB  - AIMS: To study the prognostic role of beta-catenin and stem cell markers in
      medulloblastoma (MB). MATERIALS AND METHODS: Sixty cases of MB were
      retrospectively analyzed to study the expression of beta-catenin, CD15, and CD133
      by immunohistochemistry. Their expression was correlated with histological
      subtypes and event-free survival (EFS). Patients were divided into Group 1 and 2
      based on non-occurrence and occurrence of events during the follow-up period.
      RESULTS: Fifty of the 60 cases were of classic type of MB while nine were of
      desmoplastic subtype and one case showed chondroid and rhabdomyoblastic
      differentiation. Immunoreactivity for beta-catenin was observed as nuclear and/or
      cytoplasmic positivity within the tumor cells. Forty-one (68.3%) cases showed
      cytoplasmic positivity, while nuclear positivity was seen in 21 (35%) cases.
      There was a significant correlation between nuclear expression of beta-catenin
      and different histological subtypes by Chi-square test (P value<0.05). A
      statistically significant positive correlation of beta-catenin nuclear positivity
      with EFS was observed. Among 60 cases, 37 cases (67.3%) showed presence of CD15+
      tumor cells with percentage of positivity varying between 0.1 to 17.1%. Overall,
      42 of 60 (70%) cases showed presence of CD133+ cells. The percentage of
      positivity varied between 0.1 to 16.5%. A statistically significant negative
      correlation of CD15 and CD133 positivity with EFS was observed. CONCLUSIONS:
      Nucleopositive beta-catenin cases were associated with a favorable outcome on
      univariate analysis. Both CD15 and CD133 positivity were associated with a worse
      outcome on univariate analysis.

PMID- 23135026
TI  - Microvascular decompression of cochleovestibular nerve in patients with tinnitus
      and vertigo.
AB  - AIM: The aim of this study was to investigate the patient selection, indications
      for operation, surgical methods and effects of microvascular decompression (MVD)
      for treatment of intractable and incapacitating tinnitus and vertigo. MATERIALS
      AND METHODS: A total of 35 patients were recruited from January 2009 to June 2010
      for the MVD surgery. RESULTS: Arterial compression of cochleovestibular nerve was
      found in all the 35 patients. The immediate effect of MVD was observed in 22
      patients with tinnitus and 10 patients with vertigo. The follow-up data for the
      effect of MVD showed complete resolution of tinnitus in 14 patients and vertigo
      in 6 patients. CONCLUSIONS: Vascular compression of cochleovestibular nerve in
      cerebellopontine angle may be one of the causes of intractable and incapacitating
      tinnitus and/or vertigo. MVD may be a safe and effective surgical procedure for
      treatment of severe tinnitus and/or vertigo in patients.

PMID- 23135027
TI  - Genetics of ischemic stroke: Indian perspective.
AB  - A stroke is still a major cause of long-term disability and the third largest
      killer in the world after heart attack and cancer. Inherited genetic variation
      has been shown to play a role in its pathogenesis and therefore, there is a need
      to identify the culprit genetic variants. They may provide novel targets for
      preventive therapeutics. The most intensively investigated candidate gene is
      PDE4D. There are several positive replication studies of PDE4D gene with stroke.
      The genetic contribution to ischemic stroke risk in India has not been explored
      adequately. Reports on few candidate genes are available but we are still lagging
      behind in this aspect. Most of the reports are from Andhra Pradesh, a province in
      south India and a few parts of north India. PDE4D has been identified as a
      predisposition gene for ischemic stroke in Southern as well as the Northern
      population of India.

PMID- 23135028
TI  - Association of CYP11B2 gene polymorphism with ischemic stroke in the north
      Chinese Han population.
AB  - BACKGROUND: Genetic variations of renin-angiotensin-aldosterone system play an
      important role in the pathogenesis of hypertension and stroke. AIM: To
      investigate the -344C/T and intron 2 conversion polymorphisms of aldosterone
      synthase gene (CYP11B2) for an association with stroke and hypertension in the
      North Chinese Han population. MATERIALS AND METHODS: This case-control study
      included 332 patients and 250 controls. Genotypes of -344C/T polymorphism was
      determined by polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP) and the intron 2 conversion polymorphism was genotyped using two
      separated PCRs. RESULTS: There were significant differences in genotype
      frequencies of -344C/T polymorphism between stroke patients and controls (P =
      0.002). An association was found between TT genotype and ischemic stroke [odds
      ratio = 1.572, 95%CI (1.095-2.258), P = 0.014]. However, there was no significant
      association of intron 2 polymorphism with stroke. Furthermore, when the ischemic
      stroke patients were classified according to Trial of Org 10172 in Acute Stroke
      Treatment classification, TT genotype was found to be associated with large
      artery atherosclerosis [odds ratio = 1.747, 95%CI (1.182-2.584), P = 0.005] and
      small vessel disease [odds ratio = 1.781, 95%CI (1.134-2.796), P = 0.012]. The
      intron 2 polymorphism failed to show relationship with any specific stroke
      subtype. CONCLUSIONS: Our findings suggest a significant association of CYP11B2 (
      344C/T) polymorphism with stroke but intron 2 polymorphism is not associated with
      increased stroke susceptibility.

PMID- 23135029
TI  - Cytoskeletal and extracellular matrix alterations in limb girdle muscular
      dystrophy 2I muscle fibers.
AB  - In this detailed muscle biopsy study of a patient with molecularly confirmed
      diagnosis of limb-girdle muscular dystrophy 2I (LGMD2I) we show some new data,
      that is the presence of altered expression pattern of costamere components as
      integrin alpha7B and integrin beta1D associated with vinculin costameric
      derangement and basal lamina ultrastructural abnormalities as detachments and
      discontinuities suggesting that different cellular compartments are involved in
      LGMD2I and the altered basement membrane-plasmalemma-cytoskeleton binding can
      underlie muscle degeneration.

PMID- 23135030
TI  - Combined involvement of muscle, nerve, and myoneural junction following
      leptospira infection.
AB  - Leptospirosis is a zoonosis prevalent worldwide and is endemic in many parts of
      India. In early leptospiremic as well as late immune phase of the disease kidney,
      liver, heart, and lungs are commonly involved. Neurological manifestations are
      rare but may occur during immune phase in the form of aseptic meningitis,
      meningoencephalitis, seizures, myelitis, polyradiculoneuritis, and myalgia. In
      this report, we describe a rare case of leptospirosis with combined involvement
      of nerve, muscle, and myoneural junction in generalized fashion along with
      pulmonary, renal, and hepatic dysfunction.

PMID- 23135031
TI  - A surgical case of paraclinoid carotid aneurysm associated with ipsilateral
      cervical internal carotid artery dissection.
AB  - This report presents a 60-year-old with a large paraclinoid carotid aneurysm
      associated with cervical interal carotid artery (ICA) dissection (CICAD). She had
      a fall while riding a bicycle and hit her head on the ground. Computed tomography
      scan done at another facility showed a round mass lesion near the sella. Her
      medical history revealed gradual decrease in left eye vision since two years.
      Left carotid artery digital subtraction angiography demonstrated a CICAD with an
      intimal flap and a large paraclinoid aneurysm (15.5 mm in size). She underwent a
      high-flow bypass with a so-called double-insurance bypass and proximal ligation
      of the cervical ICA and the postoperative course was uneventful. She was
      discharged without any new neurological deficits. We suggest that the possible
      nature of carotid artery dissection (CAD)-related hemodynamic changes should be
      taken into consideration in cases of intracranial aneurysm associated with CAD.

PMID- 23135032
TI  - Bow hunter's stroke - a rare presentation of CV junction anomaly: case report.

PMID- 23135033
TI  - Isolated bilateral basal ganglionic hyper intensities in early stage of
      subacutesclerosing panencephalitis: a case report.

PMID- 23135034
TI  - Unusual central nervous system presentation of ALK-positive anaplastic large cell
      lymphoma in a child.

PMID- 23135035
TI  - Nemaline myopathy and pregnancy: a challenge indeed.

PMID- 23135036
TI  - Choreoathetosis in herpes simplex encephalitis relapse with bilateral thalamic
      gliotic lesions on magnetic resonance imaging.

PMID- 23135037
TI  - Anterior interosseous nerve involvement in a patient due to weight lifting: MRI
      and EMG finding.

PMID- 23135038
TI  - Transient ventricular bigeminy during vertebral artery catheterization.

PMID- 23135039
TI  - Spontaneous disappearance of the pituitary macroadenoma after apoplexy: a case
      report and review of the literature.

PMID- 23135040
TI  - Axillary fold and scapular hump in spinal accessory nerve injury.

PMID- 23135041
TI  - Unusual clinical and imaging characteristics in a patient with voltage-gated
      potassium channel antibody-associated encephalitis.

PMID- 23135042
TI  - Ossified rathke's cleft cyst: a rare variant.

PMID- 23135043
TI  - Primary solitary malignant hemangioendothelioma of vertex: a rare calvarial
      tumor.

PMID- 23135044
TI  - Complicated lumbar ganglioneuroma.

PMID- 23135045
TI  - Giant thoracolumbar extradural arachnoid cyst: an uncommon cause of spine
      compression.

PMID- 23135046
TI  - Giant intradiploic dermoid cyst of the frontal bone with involvement of frontal
      sinus in an elderly patient.

PMID- 23135047
TI  - Primary presacral carcinoid tumor with gluteal muscle metastasis.

PMID- 23135048
TI  - Squamosal type superficial middle cerebral vein: a rare venous drainage pattern.

PMID- 23135049
TI  - Agenesis of internal carotid artery with anterior communicating artery aneurysm.

PMID- 23135050
TI  - Meningioma mimics chronic subdural hematoma: a case report and discussion of
      differential diagnosis.

PMID- 23135051
TI  - Unusual presentation of occipital condyle fracture: contralateral hypoglossal
      nerve palsy.

PMID- 23135052
TI  - Synchronous occurrence of a ruptured skull base teratoma and an expansile
      porencephalic cyst presenting with proptosis.

PMID- 23135053
TI  - Unusual presentation in adult medulloblastomas: imaging features mimicking
      cerebellar dysplastic gangliocytoma (Lhermitte-Duclos disease).

PMID- 23135054
TI  - Giant colloid cyst of third ventricle with microhemorrhages causing neurological
      deterioration: a very rare presentation.

PMID- 23135055
TI  - Vein of Galen aneurysmal malformation: strategy transarterial embolization using
      coils alone.

PMID- 23135056
TI  - Lumbosacral actinomycosis with direct involvement and compression of conus
      medullaris and cauda equina nerve roots: an extremely rare case.

PMID- 23135057
TI  - Bilateral petrous apex cephaloceles.

PMID- 23135058
TI  - Rheumatoid nodule presenting as Morton's neuroma.
AB  - Among 101 feet that presented with symptoms and signs similar to Morton's
      neuroma, intermetatarsal rheumatoid nodules were found in five feet (three
      patients). Two patients had bilateral involvement. Histology of the excised
      tissue showed the presence of a rheumatoid nodule and Morton's neuroma in four
      feet and a rheumatoid nodule with unremarkable nerve bundles in one. A rheumatoid
      nodule can coexist with Morton's neuroma, as seen in our patients, and the
      presentation is often similar to that of a Morton's neuroma. Our patients were
      rendered asymptomatic with surgical treatment and went on to have appropriate
      management of rheumatoid arthritis. Rheumatoid nodule should be considered in the
      differential diagnosis of Morton's neuroma in not only rheumatoid arthritis
      patients but also asymptomatic patients who have never been tested for rheumatoid
      antibodies.

PMID- 23135059
TI  - Changes in electric properties of human breast cancer cells.
AB  - Studies of the electrical surface properties of biological cells have provided
      fundamental knowledge about the cell surface. The change in biological functions
      of cells may affect the surface properties and can be detected by electrokinetic
      measurements. The surface density of fibroblasts and breast cancer cells (MDA-MB
      231 and MCF-7) as a function of pH was measured by electrophoresis. The
      interaction between solution ions and the breast cancer cell or fibroblast
      surface was described by a four-component equilibrium model. The agreement
      between the experimental and theoretical charge variation curves of the breast
      cancer cells and fibroblasts was good at pH 2.5-9. The extent of fibroblast and
      breast cancer cell lipid peroxidation was estimated by HPLC measurement of the
      malondialdehyde level. The acid (C(TA)) and basic (C(TB)) functional group
      concentrations and the average association constant with hydroxyl (K(BOH)) ions
      values of the breast cancer cell membranes were higher than in normal cells,
      while the average association constant with hydrogen (K(AH)) value was smaller.
      The level of lipid peroxidation products was higher in breast cancer cells than
      in normal cells.

PMID- 23135060
TI  - Ionic currents of human trabecular meshwork cells from control and glaucoma
      subjects.
AB  - Increasing evidence suggests that trabecular meshwork (TM) cells participate in
      the regulation of intraocular pressure by controlling the rate of filtration of
      the aqueous humor. Ionic conductances that regulate cell volume and shape have
      been suggested to play an important role in TM cell volume regulation. Here, we
      compared ionic currents from TM cells derived from a normal subject (CTM) and
      from an individual affected by glaucoma (GTM). We found that while the ionic
      current types were similar, the current amplitudes and percentage of cells
      endowed with specific current at baseline were different in the two cell lines.
      Thus, we found that the majority of CTM cells were endowed with a swelling
      activated Cl(-) current at baseline, whereas in the majority of GTM cells this
      current was not active at baseline and became activated only after perfusion with
      a hypotonic solution. An inward rectifier K(+) current was also more prevalent in
      CTM than in GTM cells. Our work suggests that disregulation of one or more of
      these ionic currents may be at the basis of TM cell participation in the
      development of glaucoma.

PMID- 23135061
TI  - Tropical storm off Myanmar coast sweeps reefs in Ritchie's Archipelago, Andaman.
AB  - The reefs in some islands of Andaman and Nicobar suffered severe damage following
      a tropical storm in the Bay of Bengal off Myanmar coast during 13-17 March 2011.
      Surveys were conducted at eight sites in Andaman, of which five were located in
      the Ritchie's Archipelago where maximum wind speeds of 11 m s(-1) was observed;
      and three around Port Blair which lay on the leeward side of the storm and had
      not experienced wind speeds of more than 9 m s(-1). Corals in the shallow inshore
      reefs were broken and dislodged by the thrust of the waves. Significant damage in
      the deeper regions and offshore reefs were caused by the settlement of debris and
      sand brought down from the shallower regions. The fragile branching corals
      (Acropora sp.) were reduced to rubbles and the larger boulder corals (Porites
      sp.) were toppled over or scarred by falling debris. The reefs on the windward
      side and directly in the path of the storm winds were the worst affected. The
      investigation exposes the vulnerability of the reefs in Andaman to the
      oceanographic features which generally remain unnoticed unless the damage is
      caused to the coastal habitats.

PMID- 23135062
TI  - Integrated prevention services for HIV infection, viral hepatitis, sexually
      transmitted diseases, and tuberculosis for persons who use drugs illicitly:
      summary guidance from CDC and the U.S. Department of Health and Human Services.
AB  - This report summarizes current (as of 2011) guidelines or recommendations
      published by multiple agencies of the U.S. Department of Health and Human
      Services (DHHS) for prevention and control of human immunodeficiency virus (HIV)
      infection, viral hepatitis, sexually transmitted diseases (STDs), and
      tuberculosis (TB) for persons who use drugs illicitly. It also summarizes
      existing evidence of effectiveness for practices to support delivery of
      integrated prevention services. Implementing integrated services for prevention
      of HIV infection, viral hepatitis, STDs, and TB is intended to provide persons
      who use drugs illicitly with increased access to services, to improve timeliness
      of service delivery, and to increase effectiveness of efforts to prevent
      infectious diseases that share common risk factors, behaviors, and social
      determinants. This guidance is intended for use by decision makers (e.g., local
      and federal agencies and leaders and managers of prevention and treatment
      services), health-care providers, social service providers, and prevention and
      treatment support groups. Consolidated guidance can strengthen efforts of health
      care providers and public health providers to prevent and treat infectious
      diseases and substance use and mental disorders, use resources efficiently, and
      improve health-care services and outcomes in persons who use drugs illicitly. An
      integrated approach to service delivery for persons who use drugs incorporates
      recommended science-based public health strategies, including 1) prevention and
      treatment of substance use and mental disorders; 2) outreach programs; 3) risk
      assessment for illicit use of drugs; 4) risk assessment for infectious diseases;
      5) screening, diagnosis, and counseling for infectious diseases; 6) vaccination;
      7) prevention of mother-to-child transmission of infectious diseases; 8)
      interventions for reduction of risk behaviors; 9) partner services and contact
      follow-up; 10) referrals and linkage to care; 11) medical treatment for
      infectious diseases; and 12) delivery of integrated prevention services. These
      strategies are science-based, public health strategies to prevent and treat
      infectious diseases, substance use disorders, and mental disorders. Treatment of
      infectious diseases and treatment of substance use and mental disorders
      contribute to prevention of transmission of infectious diseases. Integrating
      prevention services can increase access to and timeliness of prevention and
      treatment.

PMID- 23135063
TI  - Songs of two starling species: common traits versus adaptations to the social
      environment.
AB  - We analysed, for the first time, songs of the African Red-winged Starling
      Onychognathus morio and compared their general characteristics with those of the
      European Starling Sturnus vulgaris. Both species are gregarious during the non
      breeding season, but European Starlings tend to nest in colonies, form unstable
      pair-bonds and are occasionally polygynous, whereas Red-winged Starlings form
      long-term pair-bonds and occupy exclusive nesting territories. Red-winged
      Starlings produced the same basic song categories as European Starlings: warbles
      and whistles. These two categories appeared to be involved in similar social
      interactions in the two species. However, several aspects of song behaviour
      differed between the two species: Red-winged Starlings, breeding in isolated
      nests, preferentially used whistles for long-distance communication and showed a
      simpler organization of warbling song. Whistles in the Red-winged Starling were
      mostly shared between birds and, in contrast to the European Starling, were not
      indicators of individual identity. Also in contrast to the European Starling,
      female song in Red-winged Starlings appeared very important throughout the
      breeding period. Our results suggest that some song characteristics in the two
      species are phylogenetically conserved whereas others are affected by the
      distinct social systems of the two species.

PMID- 23135064
TI  - A Ru-isocyanate initiator for fast, living, precisely controlled ring-opening
      metathesis polymerization at ambient temperatures.
AB  - The new complex Ru(NCO)(2)(IMes)(py)(2)(=CHPh) is the first ruthenium metathesis
      initiator capable of fast, controlled living polymerization of functionalized
      norbornenes at room temperature, irrespective of monomer bulk.

PMID- 23135066
TI  - Large and giant vestibular schwannomas: does cisterna magna hyperproteinorrhachia
      influence visual status?
AB  - BACKGROUND: Hyperproteinorrhachia associated with vestibular schwannomas (VSs)
      may influence visual status independent of the effect caused by raised
      intracranial pressure. The role of cisterna magna CSF protein levels (CMCP) in
      determining visual outcome in patients with large to giant vestibular schwannomas
      (VSs) was prospectively investigated. METHODS: The mean CMCP levels in VSs and
      control group; and, levels in VSs with or without visual deterioration were
      compared. Spearman's rank correlation coefficient tested for relationships
      between CMCP level with symptom duration and tumour volume (Kawamoto's method).
      Vision was regarded as normal when visual acuity was >6/18; and, deteriorated
      when it was between 6/18 and PL negative in the worse eye. Papilloedema (n =
      26)/secondary optic atrophy (n = 6) and hydrocephalus (based on Evan's ratio,
      mild to moderate: n = 22; none: n = 18) were also recorded. The analysis of
      factors predicting diminished vision was done using logistic regression analysis
      (p < 0.05 significant). FINDINGS: There was a significant difference (p < 0.001)
      in mean CMCP levels between VS (456.3 SD 213.6 mg/dl) and control groups (96.3 SD
      74.3 mg/dl). The mean CMCP levels in the VS group were also markedly higher than
      the ventricular mean protein levels. The CMCP levels in patients with visual
      diminution (<6/18 to PL negative; n = 23) was 561.4 SD 186.9 mg/dl and those
      without visual loss (n = 17) was 314.2 SD 160.8 mg/dl (p < 0.001). Their grade of
      visual diminution had a positive correlation with mean CMCP levels (p < 0.001).
      There was a negative correlation between total duration of symptoms and CMCP
      levels (p < 0.015). Logistic regression analysis using five independent factors
      (symptom duration, papilloedema/secondary optic atrophy, tumour volume,
      hydrocephalus and mean CMCP level) revealed that only CMCP level had a
      significant association with visual diminution. CONCLUSION: Elevated cisternal
      CSF proteins may play an important role in determining visual outcome in large to
      giant VSs. Ventricular CSF analysis is often unable confirm the presence of VS
      associated cisternal hyperproteinorrhachia. High CMCP levels may influence
      decision-making while instituting a permanent CSF diversion for postoperative
      hydrocephalus or recalcitrant pseudomeningocoele.

PMID- 23135067
TI  - Eyebrow craniotomy for anterior skull base lesions: how I do it.
AB  - BACKGROUND: The eyebrow craniotomy is a less invasive alternative approach for
      accessing anterior skull base lesions, compared to traditional and more extensive
      exposures. We give a stepwise description of this minimally invasive technique
      with discussion on the indications, limitations and key aspects of perioperative
      management. METHODS: Positioning of the head and planning the surgical corridor
      are dictated by the nature, site and size of the target lesion. The eyebrow
      incision should spare the medial and posterolateral neural structures.
      Microsurgical strategy is based on opening up the basal cisterns and respecting
      the distorted neurovascular anatomy. Selective use of brain retractor and
      angulation of the operative microscope enable the surgeon to make use of the
      "keyhole effect" for accessing a larger target. Perioperative measures are in
      part dictated by the nature of the pathology, involvement of the optic apparatus
      and changes to pituitary function. CONCLUSION: The eyebrow craniotomy may be
      safely used as a minimally invasive approach for a variety of anterior skull base
      lesions. There is an operative learning curve and some types of pathologies are
      easier to approach by this technique than others. KEY POINTS: * The eyebrow
      craniotomy is an alternative less invasive approach for accessing anterior skull
      base lesions * Positioning of the head and planning the surgical corridor are
      dictated by the nature, site and size of the target lesion * Microsurgical
      strategy is based on opening up the basal cisterns and respecting the distorted
      neurovascular anatomy. * Selective use of brain retractor and angulation of the
      operative microscope enable the surgeon to make use of the "keyhole effect" for
      accessing a larger target * Perioperative measures are in part dictated by the
      nature of the pathology, involvement of the optic apparatus and changes to
      pituitary function. * There is an operative learning curve and some types of
      pathologies are easier to approach by this technique than others.

PMID- 23135068
TI  - From the Editor-in-Chief.

PMID- 23135069
TI  - Knowledge of termination of pregnancy (TOP) legislation and attitudes toward TOP
      clinical training among medical students attending two South African
      universities.
AB  - Provision of safe, voluntary, termination of pregnancy (TOP) in South Africa is
      challenged by an insufficient number of TOP-trained clinicians. Medical students'
      understanding of TOP legality and their attitudes toward TOP training are
      indicators for future service provision. We administered a 63-item questionnaire
      to explore these issues at the University of Cape Town and Walter Sisulu
      University. Ordinary least squares regression assessed predictors of TOP
      legislation knowledge and training attitudes. RESULTS: Of 1308 students, 95% knew
      that TOP was legal in South Africa, but few (27%) understood the specific
      provisions of the legislation beyond 13 weeks' gestation. Sixty-three percent
      desired more information about TOP. In multivariate models, female, white and
      sexually experienced students and students more advanced in school had better
      legislation knowledge (all p < .01). Attending religious services regularly (p <
      .01) was associated with lack of support for TOP training, whereas being in a
      relationship (p < .01) was associated with support for TOP training.

PMID- 23135070
TI  - Household expenditures as a measure of socioeconomic status among Iraqis
      displaced in Jordan and Syria.
AB  - BACKGROUND: Various measures are used to represent socioeconomic status (SES) in
      health research, including income. However, reliability of income data can be
      low. Household expenditures are an accepted proxy for income as a more reliable
      measure but have been studied little in refugee populations. METHODS: Health and
      SES measures from cross-sectional surveys of Iraqi refugees in Jordan and Syria
      were analyzed using logistic regression to assess the interchangeability of
      household income and expenditures. RESULTS: In Jordan, odds ratios in the
      regression models including income quartiles were frequently similar to odds
      ratios found in the models including expenditure quartiles, indicating
      interchangeability. In Syria, fewer similarities were observed. CONCLUSIONS: This
      study provides some evidence that household expenditures may be used
      interchangeably with household income for some populations, allowing for the
      potential collection and use of data related to expenditures as a measure of SES,
      similar in importance to that of income.

PMID- 23135071
TI  - Trends and determinants of condom use in Uganda.
AB  - BACKGROUND: Documenting trends in condom use and exploring factors associated
      with their utilization are important for broadening the information base for the
      design of HIV intervention programs. This paper aims to document Uganda's
      nationwide trends in condom use from 1995 to 2006 and seeks to understand some of
      the socio-demographic variables that may be associated with their use, using
      Uganda Demographic Health Surveys (UDHSs). METHOD: Data from UDHSs conducted in
      1995, 2000/2001 and 2006 were analyzed. Socio-demographic variables as well as
      'survey year' were selected to assess their interaction with condom use.
      Multivariate regression analyses were performed. Odds ratios and confidence
      intervals were computed. RESULTS: Socio-demographic factors such as being male
      and living in an urban setting were significantly associated with an increased
      likelihood of reported use of condoms. All results indicated a far greater
      increase in condom use between 1995 and 2000/2001 than between 2000/2001 and
      2006. CONCLUSION: Policies need to intensify condom use campaigns especially
      among women and rural populations. The wane in increase in condom use between
      2000/2001 and 2006 may be due to the large-scale influx of antiretrovirals
      (starting in 2004) which may be lowering the anxiety associated with the social
      construct of HIV/AIDS.

PMID- 23135072
TI  - Engaging men in family planning services delivery: experiences introducing the
      Standard Days Method(r) in four countries.
AB  - Family planning is often regarded as the woman's responsibility, but there is
      growing recognition of the need to involve men in family planning programs. Since
      2001, the fertility-awareness-based Standard Days Method(r) (SDM) has been
      introduced in more than 30 countries, providing a natural, effective birth
      control option. SDM requires the cooperation of the male partner, and its
      introduction created an opportunity to test innovative strategies to engage
      couples in family planning. Such strategies included couple counselling, outreach
      activities that encouraged men to participate in family planning and integration
      of family planning into traditionally male programs. Due to the SDM's intrinsic
      characteristics as a couple method, SDM providers are sensitized to the
      importance of exploring other critical sexual and reproductive health topics,
      including intimate partner violence, HIV, sexuality and partner communication.
      This paper presents several case studies describing how men were engaged in SDM
      introduction activities in four countries.

PMID- 23135073
TI  - Melanoma-detecting technologies and standard of care.

PMID- 23135074
TI  - Metformin-induced pseudoporphyria.

PMID- 23135075
TI  - Fractional laser skin resurfacing.
AB  - Laser skin resurfacing (LSR) has evolved over the past 2 decades from traditional
      ablative to fractional nonablative and fractional ablative resurfacing.
      Traditional ablative LSR was highly effective in reducing rhytides, photoaging,
      and acne scarring but was associated with significant side effects and
      complications. In contrast, nonablative LSR was very safe but failed to deliver
      consistent clinical improvement. Fractional LSR has achieved the middle ground;
      it combined the efficacy of traditional LSR with the safety of nonablative
      modalities. The first fractional laser was a nonablative erbium-doped yttrium
      aluminum garnet (Er:YAG) laser that produced microscopic columns of thermal
      injury in the epidermis and upper dermis. Heralding an entirely new concept of
      laser energy delivery, it delivered the laser beam in microarrays. It resulted in
      microscopic columns of treated tissue and intervening areas of untreated skin,
      which yielded rapid reepithelialization. Fractional delivery was quickly applied
      to ablative wavelengths such as carbon dioxide, Er:YAG, and yttrium scandium
      gallium garnet (2,790 nm), providing more significant clinical outcomes.
      Adjustable laser parameters, including power, pitch, dwell time, and spot
      density, allowed for precise determination of percent surface area, affected
      penetration depth, and clinical recovery time and efficacy. Fractional LSR has
      been a significant advance to the laser field, striking the balance between
      safety and efficacy.

PMID- 23135076
TI  - Facial tightening with an advanced 4-MHz monopolar radiofrequency device.
AB  - BACKGROUND: Over the past 10 years, radiofrequency (RF) technology has been
      utilized for nonablative treatments for the treatment of rhytides and skin
      laxity. This manuscript reviews the scientific background of collagen synthesis
      in vivo and in response to RF energy as well as a clinical study of 17 patients
      receiving a series of facial treatments with a 4-MHz monopolar RF (Pelleve,
      Ellman International, Inc, Oceanside, NY). Clinical methods, results, and a
      review of the literature for RF aesthetic treatments of the face are presented.
      METHODS: Seventeen patients were treated in one site with 6 total treatments
      scheduled as follows: 1 session was performed every 15 days for 2 consecutive
      sessions, 1 session every month for 2 consecutive sessions, and 1 session every 2
      months for 2 consecutive sessions. Both the treating physician and the patients
      via live viewing and comparison with baseline photographs performed assessment of
      results. Results are reported as averages across the 17 patients. RESULTS: Two
      weeks after the first treatment, patients noted an overall average of 25% to 30%
      improvement. Just before the last or sixth treatment, there was an average of 50%
      improvement noted by the physician, with patients ranking an average self
      improvement of 48%. The treating physician rated average improvement of 46%
      compared with baseline, whereas the patients ranked average improvement of 30%
      compared with baseline at 1 year after treatment was initiated (6 months after
      the final treatment). Patients find this treatment to be very well tolerated,
      with minimal to no discomfort and no downtime or significant side effects.
      CONCLUSIONS: The Pelleve 4-MHz monopolar RF device is effective, safe, and very
      well tolerated for treating laxity, texture, and wrinkles of the skin without
      complication or discomfort. Evidence in the literature supports the scientific
      mechanism of action of acute collagen modification and continued neocollagenesis
      observed with the system. In this cohort, patients maintain approximately 50%
      improvement on average at 6 months and a 30% to 50% improvement 1 year after
      beginning the treatments, 6 months after completion.

PMID- 23135077
TI  - The evolution of quality-switched lasers.
AB  - Quality-switched (QS) lasers and their applications have evolved greatly since
      the ruby laser's effect on tattoo ink was first reported in the 1960s. The 1983
      description of selective photothermolysis explained the efficacy of QS lasers for
      the treatment of cutaneous pigmented lesions and tattoos and cemented their
      status as the gold standard for these targets. Within the past decade, the uses
      for QS lasers have expanded dramatically, including nonablative rejuvenation and
      the treatment of onychomycosis. Additional applications and refined techniques
      and technologies promise to maintain the stature of QS lasers as an integral part
      of the laser surgeon's arsenal.

PMID- 23135078
TI  - Fractional, nonablative Q-switched 1,064-nm neodymium YAG laser to rejuvenate
      photoaged skin: a pilot case series.
AB  - BACKGROUND: Scientific research in the field of energy-based and light-based
      procedures made it possible to develop a very new and innovative generation of
      lasers that combine the benefit of a nonablative and a fractional laser device,
      promising skin rejuvenation without harming the epidermis. With this pilot case
      series, we performed one of the first systematic reports evaluating efficacy and
      safety of the fractional, nonablative Q-switched 1,064-nm neodymium-doped yttrium
      aluminum garnet (Nd:YAG) laser device in the treatment of rhytides of the face,
      neck, and chest. METHODS: Seven healthy female subjects (mean +/- standard
      deviation age, 53.8 +/- 10.0 years) with visible signs of facial and neck skin
      aging were treated with fractional, nonablative Q-switched 1,064-nm Nd:YAG laser
      device (Pixel QS Nd:YAG; Alma Lasers Ltd, Caesarea, Israel). Treated areas were
      the face, including the periorbital and perioral regions (particularly the upper
      lip), neck, and chest. Treatments consisted of 3 sessions at 2- to 4-week
      intervals. Follow-up was performed monthly following the final treatment. The
      Alexiades-Armenakas Comprehensive Grading Scale of Skin Aging was employed to
      assess efficacy. Pain ratings were recorded by 10-point visual assessment
      scoring. RESULTS: Employing the validated, quantitative grading scale for
      rhytides of the face and neck, a 0.29 grade improvement, or 11.3% improvement,
      over baseline grade was observed in the 7-subject cohort that completed follow-up
      following a mean of approximately 2 treatments at approximately 1-month follow
      up. No pain and rapidly resolving minimal erythema were noted in all subjects
      during treatment. CONCLUSION: The results of this pilot case series suggest that
      the treatment with the fractional, nonablative Q-switched 1,064-nm Nd:YAG laser
      device significantly improves superficial rhytides. With its outstanding safety,
      it seems to be particularly suitable for the treatment of sensitive areas, such
      as the periorbital region, lips, neck, and chest. The Q-switched Nd:YAG laser is
      a facile, safe, and fast treatment for aesthetic skin rejuvenation.

PMID- 23135079
TI  - Safety and efficacy of a new device combining radiofrequency and low-frequency
      pulsed electromagnetic fields for the treatment of facial rhytides.
AB  - BACKGROUND: A distinct trend in aesthetic medicine is the patient's demand for
      efficient, noninvasive treatments with no downtime. Ongoing with this, these so
      called lunchtime procedures are expected to be as safe and painless as possible.
      A new technique based on a combination of radiofrequency (RF) and pulsed
      electromagnetic fields (PEMF) was recently introduced and is supposed to be
      effective in the treatment of facial wrinkles and virtually pain free. The
      objective of this study was to investigate the safety and efficacy of this
      technology for the treatment of facial rhytides. METHODS: Thirty-one subjects
      with facial wrinkles and rhytides were entered into this study. Every subject
      received 10 treatments of the face with a device that combines 1 MHz
      radiofrequency with PEMF with a flux of 15 gauss. Patients rated the pain level
      immediately after the treatment by using a visual analog scale (VAS) for pain.
      Side effects were recorded at every visit. The study's efficacy end point was
      evaluated by 2 blinded physicians who rated the standardized pictures from
      baseline and 3-month follow-up using the Fitzpatrick Wrinkle and Elastosis Scale
      (FWES). RESULTS: No unexpected adverse side effects were detected or reported for
      the duration of the study. Both raters recognized improvements of at least 1
      grade on the FWES in 30 of 31 subjects (97%). The score decreased from 5.2 before
      the first treatment to 3.6 at 3 months after the last treatment. Furthermore, all
      patients rated the treatment to be free of pain on the VAS pain scale.
      CONCLUSION: The results of this study show that the combination of multipolar RF
      with PEMF is a safe, effective, and painless approach to treat facial rhytides
      and is suitable to answer the demands of patients for safe treatments without
      pain or downtime.

PMID- 23135080
TI  - Split-face comparison of ultrapulse-mode and superpulse-mode fractionated carbon
      dioxide lasers on photoaged skin.
AB  - BACKGROUND: Both ultrapulse-mode and superpulse-mode fractional CO2 lasers (UPCO2
      and SPCO2) could be successfully used in treating photoaged skin. OBJECTIVE: This
      evidence-based study was intended to compare the therapeutic and adverse effects
      of UPCO2 and SPCO2 in treating photoaged skin in Chinese subjects. METHODS:
      Eighteen Chinese subjects with Fitzpatrick skin type IV were enrolled in a
      randomized, split-face trial. Subjects received SPCO2 on one half of the face and
      UPCO2 on the other half. Before and after photos, skin color, epidermal water
      content, sebum level, periorbital wrinkles, skin roughness, and self-esteem
      questionnaires were used. RESULTS: Global evaluation and subjects' self-esteem
      assessments showed a similar trend at 1-month and 3-month follow-up visits on
      both sides. The UPCO2 laser has a shorter downtime of 6.25+/-2.71 days compared
      with 6.41+/-2.67 days for SPCO2, but has a higher incidence of edema, spot
      bleeding, prolonged redness and postinflammatory hyperpigmentation. More subjects
      prefer SPCO2 treatment because of similar efficacy and fewer adverse effects.
      CONCLUSION: The effectiveness of the SPCO2 laser in treating photoaged skin is
      very similar to the UPCO2 laser, with less erythema, but more crusting and longer
      downtime.

PMID- 23135081
TI  - Treatment of melasma and the use of intense pulsed light: a review.
AB  - Melasma is a complex multifactorial disorder whose pathogenesis is not well
      understood. In addition to increased pigmentation, increased vascularity
      associated with pigmentation is present. A variety of topical treatments
      targeting pigmentation are available with temporary improvement of mainly the
      epidermal components of melasma. Intense pulsed light (IPL) is a broadband light
      source that can target a wide range of cutaneous structures, including deeper
      pigmentation and vasculature. We describe 5 cases of persistent facial melasma
      treated with the IPL and a hydroquinone-based skin care system (Obagi Nu-Derm;
      Obagi Medical Products, Long Beach, CA), showing improvement of facial melasma
      pigmentation and vascularity.

PMID- 23135082
TI  - Treatment of sebaceous hyperplasia with a novel 1,720-nm laser.
AB  - BACKGROUND: Sebaceous hyperplasia is a common benign proliferation of sebaceous
      glands. Multiple treatment methods have been applied in the past, including
      electrodessication, ablative and visible light lasers, applications of acids, and
      photodynamic therapy. Often, however, only the superficial component of the
      lesion is treated, leading to rapid recurrence. It has been shown that human fat
      has absorption peaks at 1,210 nm and 1,720 nm. We report the first use of a novel
      1,720-nm laser in the treatment of sebaceous hyperplasia in human subjects.
      METHODS: Four patients with sebaceous hyperplasia underwent a test spot treatment
      followed by 2 full treatment sessions using the 1,720-nm laser. Photos were taken
      before treatment, at each treatment session, and 3 months following the last
      treatment. Pretreatment photographs and 3-month follow-up photographs were
      compared to assess efficacy. RESULTS: Four weeks after the final treatment, 3
      dermatologists blinded to the date of the photographs and uninvolved with the
      study evaluated the photos and scored them based on a global assessment comprised
      of: 1) lesion diameter, 2) lesion height, and 3) lesion color. Many of the
      lesions resolved almost completely after a single treatment, and no additional
      treatment was required. Overall, there was a reduction in the color, diameter,
      and height of the lesions. Crusts were noted by all patients and resolved within
      10 days. CONCLUSION: The use of this novel device that exploits the intrinsic
      selectivity of 1,720 nm achieved nearly complete clearance of sebaceous
      hyperplasia lesions without depressions or scarring. Complete heating of the
      sebaceous gland and sparing of the surrounding skin offered by this device
      resulted in clinically apparent improvement with a minimum of adverse effects.

PMID- 23135083
TI  - Treatment of benign pigmented lesions using a long-pulse alexandrite laser.
AB  - BACKGROUND: To evaluate the efficacy of a novel long-pulse alexandrite laser with
      contact cooling in the treatment of benign pigmented lesions. METHODS: Five
      patients were enrolled in the study. All patients presented with epidermal
      pigmented lesions on the arms, hands, chest, or legs. Patients were all female
      with a mean age of 59 years. At the initial evaluation, baseline pigment readings
      were determined with a pigment meter. Test spots were performed with escalating
      doses of alexandrite laser (ClearScan ALX, Sciton, Palo Alto, CA) deployed by a 7
      mm spot equipped with a 30 mm x 30 mm scanner and a 10-ms pulse duration. Contact
      cooling was used, and temperature was maintained at 18 degrees C to 20 degrees C.
      Patients returned 4 to 7 days after test spots for evaluation for the purpose of
      optimizing settings. The highest settings that allowed for epidermal preservation
      and crusting of the hyperpigmented lesions were applied for the remainder of the
      treatment zones. Determinations of improvement were made by evaluation of
      photographs with standard settings using polarized and nonpolarized images. At
      each appointment, baseline pigment measurements were made to ensure there were no
      significant changes between treatment sessions. Two treatment sessions were
      performed approximately 4 weeks apart, and the final evaluation was 3 months
      after the final treatment. RESULTS: Evaluation by a panel of blind observers
      determined a mean improvement of approximately 30%. Darker lesions responded
      better than lighter lesions. So-called low-contrast lesions performed the
      poorest. Pain was approximately 2/10 with the use of 5% lidocaine numbing cream
      applied approximately 45 minutes before each procedure. Pain was most severe
      where there was underlying hair. CONCLUSION: A long-pulse alexandrite laser
      equipped with contact cooling can achieve significant pigmentation improvement.

PMID- 23135084
TI  - Clinical evaluation of the safety and efficacy of a novel superficial and deep
      carbon dioxide fractional system in the treatment of patients with skin of color.
AB  - Fractional carbon dioxide (CO2) laser treatments have become a standard for
      treating a myriad of skin concerns. One of the biggest challenges facing us in
      this regard is treating the vast number of patients with skin of color who we
      encounter regularly in our practices. A novel superficial and deep CO2 ablative
      fractional device with both components coming from a single handpiece has been
      developed and is now being evaluated for patients with skin of color. In the 5
      patients studied, side effects were not apparent and no postinflammatory
      hyperpigmentation was identified. This initial report suggests further evaluation
      is important to enhance our ablative fractional therapies.

PMID- 23135085
TI  - The optimal filler: immediate and long-term results with emulsified silicone
      (1,000 centistokes) with cross-linked hyaluronic acid.
AB  - BACKGROUND: Silicone is one of the oldest and longest lasting of the dermal
      fillers. Microdroplet silicone injections have proven to be safe and effective.
      This paper describes how to obtain microdroplet silicone (1,000 centistokes) in a
      consistent manner, including a discussion of its efficacy and safety. METHODS AND
      MATERIALS: A simple, permanent method of tissue augmentation is described. U.S.
      Food and Drug Administration- approved liquid silicone (Silikon(r)) is emulsified
      with cross-linked hyaluronic acid through a Luer-Lok to Luer-Lok connector
      between two 3-cc syringes. This stable emulsion is injected through a 27G needle
      or through a 25G or 27G microcannula into the middermis, subcutaneous tissue, or
      periosteum. RESULTS: The results of 95 cases are described. The emulsion is most
      beneficial for distensible acne valleys, nasolabial folds, glabellar frown lines,
      augmentation of the vermilion border of the lips, and projection of the nose,
      cheekbones, and chin. Exterior nasal deviations and soft tissue defects are also
      improved. Complications are minimal and include temporary bruising, erythema, and
      mild edema. Any temporary small nodules are easily leveled with massage.
      Occasionally, it takes a repeat session at 1 month to completely elevate
      depressions. The resulting elevations remain stable during the 2-year follow-up
      period. No silicone granulomas have developed. CONCLUSIONS: This methodology has
      replaced many indications for temporary, semipermanent, or permanent fillers.

PMID- 23135086
TI  - Caffeine protects human skin fibroblasts from acute reactive oxygen species
      induced necrosis.
AB  - Oxidative damage by reactive oxygen species (ROS) plays a major role in aging and
      carcinogenesis. Little is known about either the effects of acute ROS in necrosis
      and inflammation of skin or the therapeutic agents for prevention and treatment.
      Previously, our laboratory identified caffeine as an inhibitor of hydrogen
      peroxide (H2O2)-generated lipid peroxidation products in human skin fibroblasts.
      Here, we study effects of caffeine on acute ROS-mediated necrosis. Human skin
      fibroblasts were incubated with caffeine, followed by H2O2 challenge. Flow
      cytometry was used to analyze cell morphology, counts, apoptosis and necrosis,
      and ROS. We found that caffeine protects from H2O2 cell damage at lower (0.01 mM)
      and intermediate (0.1 mM) doses. The beneficial effects of caffeine appear to be
      mediated by a mechanism other than antioxidant function.

PMID- 23135087
TI  - Impact of clobetasol propionate 0.05% spray on health-related quality of life in
      patients with plaque psoriasis.
AB  - Psoriasis causes significant distress and impairment in health-related quality of
      life (QOL) in afflicted patients. For this reason, QOL is an essential and
      important measure of treatment outcome in patients with the disease. Clobetasol
      propionate is a super-highpotent class I topical corticosteroid. The spray
      formulation is approved for twice-daily use for up to 4 weeks by patients 18
      years and older with moderate to severe plaque psoriasis. Data collected from
      2,236 patients enrolled in 5 clinical trials demonstrate consistent improvement
      in QOL measures using multiple instruments. In a randomized, double-blind trial
      in patients with scalp psoriasis, treatment with clobetasol propionate 0.05%
      spray produced significantly greater improvement in QOL compared with vehicle, as
      measured by the Scalpdex QOL instrument. In another randomized trial in patients
      with moderate to severe plaque psoriasis, clobetasol propionate 0.05% spray
      produced significantly greater reductions in mean affected body surface area and
      significantly greater improvements in QOL, as measured by the Dermatology Life
      Quality Index (DLQI), compared with a 0.05% foam formulation. When compared with
      calcipotriene/betamethasone dipropionate ointment, clobetasol propionate 0.05%
      spray produced greater rates of lesion clearance and similar improvement in QOL
      scores after 2 or 4 weeks of treatment. When clobetasol propionate 0.05% spray
      was used as monotherapy or as an add-on therapy for 4 weeks in a large,
      observational trial, approximately 80% of patients experienced consistent and
      significant improvement in QOL on 2 separate, validated QOL instruments (DLQI and
      the Koo-Menter Psoriasis Index). In conclusion, clobetasol propionate 0.05% spray
      is an efficacious and safe treatment for plaque psoriasis and produces
      significant improvement in QOL for affected patients.

PMID- 23135089
TI  - "Wet behind the ears": the postauricular training ground for local flaps.
AB  - Early in the course of surgical education, dermatologic and plastic surgery
      trainees shift from theory to practice. This shift must be done cautiously so as
      not to cause unnecessary damage to the patient, especially when attempting to
      reconstruct soft tissue defects on the face. Helical rim defects present an
      excellent opportunity because the postauricular region provides a safe
      environment for novice surgeons to practice the theoretical and manual aspects of
      basic flap reconstruction. This paper explains key features on how to plan basic
      flaps based on postauricular tissues.

PMID- 23135091
TI  - Urticaria after methyl aminolevulinate photodynamic therapy in a patient with
      nevoid basal cell carcinoma syndrome.
AB  - Methyl aminolevulinate photodynamic therapy (MAL-PDT) is utilized in several
      countries for the treatment of basal cell carcinoma, but allergic sensitization
      has been reported by the manufacturer. To the best of our knowledge, we report
      the first case of urticaria following MAL-PDT in a patient with nevoid basal cell
      carcinoma syndrome. Prophylactic use of antihistamines may allow continued use of
      MAL-PDT in this setting.

PMID- 23135092
TI  - Necrolytic acral erythema.

PMID- 23135093
TI  - The role of RNA interference in dermatology: current perspectives and future
      directions.

PMID- 23135094
TI  - Green tea catechins: biologic properties, proposed mechanisms of action, and
      clinical implications.
AB  - Botanical products, including and especially green tea leaves, have a wide range
      of both reputed and demonstrated health benefits and have been used medicinally
      for thousands of years. This paper focuses on green tea catechins, principally
      reviewing their known biologic properties and potential mechanisms of action
      (MOAs). The primary objective is to discuss the proposed antiviral,
      antiproliferative, and immunostimulatory activity of catechins based on strong
      evidence from in vitro and in vivo studies conducted to date, including two
      preclinical in vitro studies with sinecatechins, a proprietary mixture of
      catechins. This review also discusses the clinical implications of catechins for
      the treatment of external genital and perianal warts (EGWs) and other conditions
      caused by human papillomavirus (HPV). While the MOA of catechins in the treatment
      of EGWs and other HPV-related conditions may be related to or associated with
      postulated or proven antiviral and immunostimulatory activity, the precise
      clinical significance of the various in vitro findings remains largely unknown.

PMID- 23135095
TI  - The effect of hand-foot skin reaction associated with the multikinase inhibitors
      sorafenib and sunitinib on health-related quality of life.
AB  - INTRODUCTION: The multikinase inhibitors sorafenib (SO) and sunitinib (SU) have
      shown benefit in a wide range of solid tumors. Although these agents are
      generally well tolerated, they may be associated with dermatologic adverse
      events, particularly hand-foot skin reaction (HFSR). The aim of this study is to
      evaluate the impact of HFSR associated with these multikinase inhibitors on
      patient health-related quality of life (HRQOL). METHODS: Twenty-three patients
      with HFSR related to SO or SU were graded using the National Cancer Institute's
      Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 for clinical
      severity and for impact on HRQOL through completion of the patient self
      administered Skindex-16 (SK-16). Clinical severity scores were compared to HRQOL
      assessments. RESULTS: Of the 23 patients with HFSR, clinical severity was grade 1
      in 17.4%, grade 2 in 74%, and grade 3 in 8.6%. Median SK-16 scores were reported
      for symptoms (53.3), emotions (30.6), and functioning subscales (33.3). Median
      symptoms and emotions scores positively correlated with HFSR clinical severity
      grade. CONCLUSIONS: These findings demonstrate that HFSR related to SO or SU
      negatively impacts HRQOL, with the symptoms domain being most significantly
      affected. In addition, CTCAE toxicity grading correlates with HRQOL.

PMID- 23135096
TI  - Comparative study of topical 80% trichloroacetic acid with 35% trichloroacetic
      acid in the treatment of the common wart.
AB  - BACKGROUND: Common warts caused by the human papillomavirus (HPV) are considered
      to be the most common infectious skin disease. No individual treatment for common
      warts is effective as monotherapy in eradicating the lesions. The aim of this
      study is to evaluate the clinical efficacy of a 35% and an 80% trichloroacetic
      acid (TCA) solution in the treatment of the common wart. METHODS: In this single
      blinded clinical trial, 62 eligible patients with common warts referred to the
      dermatology clinic of Ghaem Hospital in Mashhad, Iran. Patients were randomly
      divided into two groups, each treated with a TCA solution (group A, TCA 80%;
      group B, TCA 35%) once per week until complete clearance of the lesions or for a
      maximum duration of six weeks. Seven patients were excluded from the final
      analysis (one patient in group A and six patients in group B) for various
      reasons, including irregular follow-up, using physical tools such as razor blades
      to remove the lesion, and failure to complete treatment; and 55 patients were
      included in the final analysis. RESULTS: Improvement to treatment responses was
      classified as: no change (no changes in the number of warts), mild (clearing of
      less than 25% of warts), moderate (clearing of 25% to 75% of warts), and good
      (clearing of more than 75% of warts). At the end of follow-up, the clinical
      improvement of group A (n=30) was: 10 patients (33.3%) with a mild response, 6
      patients (20%) with a moderate response, and 14 patients (46.7%) with a good
      response. In group B (n=25), 16 patients (64%) showed a mild response, 6 patients
      (24%) a moderate response, and 3 patients (12%) a good response. There was a
      statistically significant difference in improvement between the two treatment
      groups (P=.017). Improvement was greater with a higher concentration of TCA
      solution. CONCLUSION: This study showed that a different concentration of TCA
      solution was an effective form of treatment for common warts. Trichloroacetic
      acid 80% is more effective, but this solution must be used only with careful
      consideration by a physician.

PMID- 23135097
TI  - Isoconazole nitrate vs isoconazole nitrate and diflucortolone valerate in the
      treatment of tinea inguinalis: results of a multicenter retrospective study.
AB  - BACKGROUND AND OBJECTIVE: Many tinea inguinalis infections are characterized by
      pronounced inflammatory lesions and pruritus. Therefore, a therapy with a topical
      corticosteroid in addition to a topical antimycotic agent might be beneficial. In
      this multicenter, retrospective study, we compared the mycological and clinical
      efficacy and tolerability of isoconazole nitrate alone vs isoconazole nitrate and
      diflucortolone valerate in 58 adult patients with tinea inguinalis. PATIENTS AND
      METHODS: Treatment duration was three weeks. The efficacy of the treatment was
      based on the assessment of several signs and symptoms, which were collected on a
      4-point scale. All patients were examined clinically before the beginning of the
      treatment, one week later, two weeks later, and at the end of the treatment.
      Mycological examinations were performed before the beginning of the treatment and
      at the end of the study. RESULTS: Treatment results with the combination of
      isoconazole nitrate and diflucortolone valerate were superior regarding erythema
      and pruritus. Both erythema and pruritus resolved in a larger percentage of
      patients and more quickly. Both regimens were well tolerated. Mycological cure
      rates were similar in both groups of patients. CONCLUSIONS: Combination therapy
      with isoconazole nitrate and diflucortolone valerate is an effective and well
      tolerated regimen in adult patients with tinea inguinalis.

PMID- 23135098
TI  - A case of psoriasis verrucosa successfully treated with adalimumab.
AB  - We herein report a case of psoriasis verrucosa that was successfully treated with
      adalimumab. A 55-year-old Japanese male had a five-year history of psoriasis
      vulgaris treated with topical agents. His past history included atypical
      psychosis treated with lithium carbonate and obesity. Despite treatment,
      verrucous scales developed on erythematous plaque. After treatment with
      adalimumab, these improved remarkably, and the patient's Psoriasis Area and
      Severity Index score decreased from 16.2 to 3.7.

PMID- 23135099
TI  - Effect of bevacizumab treatment on p-boronophenylalanine distribution in murine
      tumor.
AB  - Previous studies have demonstrated that angiogenesis inhibitors can enhance tumor
      inhibitory effects of chemo- and radiotherapy via their action on tumor vessels.
      Here, we studied the effect of the angiogenesis inhibitor, bevacizumab (Avastin),
      on boron distribution in a murine tumor model. The human head and neck squamous
      cell carcinoma cell line was used for inoculation into mice. Boron-10
      concentrations in tissues were measured by prompt gamma-ray spectrometry (PGA).
      Hoechst 33342 perfusion and p-boronophenylalanine (BPA) distribution were
      determined by immunofluorescence staining. Our results revealed enhanced tumor
      blood perfusion and BPA accumulation in tumors after Avastin treatment,
      suggesting that combination of angiogenesis inhibition with treatment with boron
      compound administration may improve the efficacy of boron neutron capture therapy
      (BNCT) by modifying tumor vessels. In addition, our results also demonstrated the
      usefulness of immunofluorescence staining for investigating boron compound
      distribution at the cellular level.

PMID- 23135100
TI  - Antitumor activity of Pulsatilla koreana extract in anaplastic thyroid cancer via
      apoptosis and anti-angiogenesis.
AB  - Plants or herb extracts have emerged as a novel approach to controling various
      diseases, including cancers. Among them, Pulsatilla koreana extract (PKE) has
      been widely used as an anti-inflammatory agent and for treating dysentery in
      traditional Korean and Chinese medicine. However, the effect of PKE as a cancer
      drug candidate has been less reported. Thus, we investigated the effect of PKE on
      cell growth and its mechanism in anaplastic thyroid cancer (ATC) cells. In this
      study, PKE suppressed the growth of ATC cells in a dose-dependent manner.
      Additionally, PKE induced apoptosis by increasing expression of cleaved PARP and
      caspase-3 in ATC cells. The apoptotic effect of PKE was confirmed by diamidino-2
      phenylindole (DAPI) and terminal deoxynucleotidyltransferase-mediated nick end
      labeling (TUNEL) assay, showing apoptotic body and DNA fragmentation. In
      addition, PKE decreased the expression of hypoxia-inducible factor 1alpha (HIF
      1alpha) and vascular endothelial growth factor (VEGF) as well as inhibiting tube
      formation and migration of human umbilical vein endothelial cells (HUVECs).
      Furthermore, in vivo studies showed that PKE significantly inhibited tumor growth
      and weight in a mouse xenograft model. Taken together, the present study
      demonstrated that PKE induced apoptosis, as well as inhibiting cell growth and
      angiogenesis in ATC cells. We suggest that PKE is a potent anticancer drug
      candidate for the treatment of thyroid cancer. 

PMID- 23135101
TI  - Health care administrators' perspectives on the role of absorptive capacity for
      strategic change initiatives: a qualitative study.
AB  - BACKGROUND: The dimensions of absorptive capacity (ACAP) are defined, and the
      importance of ACAP is established in the management literature, but the concept
      has not been applied to health care organizations attempting to implement
      multiple strategic initiatives. PURPOSE: The aim of this study was to test the
      utility of ACAP by analyzing health care administrators' experiences with
      multiple strategic initiatives within two health systems. METHODOLOGY: Results
      are drawn from administrators' assessments of multiple initiatives within two
      health systems using in-depth personal interviews with a total of 61 health care
      administrators. Data analysis was performed following deductive qualitative
      analysis guidelines. Interview transcripts were coded based on the four
      dimensions of ACAP: acquiring, assimilating, internalizing/transforming, and
      exploiting knowledge. Furthermore, we link results related to utilization of
      management resources, including number of key personnel involved and time
      consumption, to dimensions of ACAP. FINDINGS: Participants' description of
      multiple strategic change initiatives confirmed the importance of the four ACAP
      dimensions. ACAP can be a useful framework to assess organizational capacity with
      respect to the organization's ability to concurrently implement multiple
      strategic initiatives. This capacity specifically revolves around human capital
      requirements from upper management based on the initiatives' location or stage
      within the ACAP framework. PRACTICE IMPLICATIONS: Strategic change initiatives in
      health care can be usefully viewed from an ACAP perspective. There is a tendency
      for those strategic initiatives ranking higher in priority and time consumption
      to reflect more advanced dimensions of ACAP (assimilate and transform), whereas
      few initiatives were identified in the ACAP "exploit" dimension. This may suggest
      that health care leaders tend to no longer identify as strategic initiatives
      those innovations that have moved to the exploitation stage or that less
      attention is given to the exploitation elements of a strategic initiative than to
      the earlier stages.

PMID- 23135102
TI  - Selective off-on fluorescent chemosensor for detection of Fe3+ ions in aqueous
      media.
AB  - A Fe(3+) chemosensor L1 was successfully synthesized with a quinoline moiety
      bound to rhodamine 6G hydrazide. The sensor L1 shows high selectivity and
      sensitivity to Fe(3+) in aqueous solution in the presence of other trace metal
      ions in organisms, abundant cellular cations and prevalent toxic metal ions in
      the environment. In addition, biological imaging and micro computed tomography
      (MCT) technology studies have demonstrated that L1 could act as a turn-on
      fluorescent chemosensor for Fe(3+) in living cells.

PMID- 23135103
TI  - Full ring closing in a diarylethene hexamer: insights from theory.
AB  - First principle simulations of an extended hexameric molecular switch are
      reported. The full switching of the system is explained by investigating the
      nature of the excited states of all possible isomers. A new multi-addressable
      asymmetric structure is proposed.

PMID- 23135104
TI  - Coaxially electrospun axon-mimicking fibers for diffusion magnetic resonance
      imaging.
AB  - The study of brain structure and connectivity using diffusion magnetic resonance
      imaging (dMRI) has recently gained substantial interest. However, the use of dMRI
      still faces major challenges because of the lack of standard materials for
      validation. The present work reports on brain tissue-mimetic materials composed
      of hollow microfibers for application as a standard material in dMRI. These
      hollow fibers were fabricated via a simple and one-step coaxial electrospining
      (co-ES) process. Poly(epsilon-caprolactone) (PCL) and polyethylene oxide (PEO)
      were employed as shell and core materials, respectively, to achieve the most
      stable co-ES process. These co-ES hollow PCL fibers have different inner
      diameters, which mainly depend on the flow rate of the core solution and have the
      potential to cover the size range of the brain tissue we aimed to mimic. Co-ES
      aligned hollow PCL fibers were characterized using optical and electron
      microscopy and tested as brain white matter mimics on a high-field magnetic
      resonance imaging (MRI) scanner. To the best of our knowledge, this is the first
      time that co-ES hollow fibers have been successfully used as a tissue mimic or
      phantom in diffusion MRI. The results of the present study provide evidence that
      this phantom can mimic the dMRI behavior of cellular barriers imposed by axonal
      cell membranes and myelin; the measured diffusivity is compatible with that of in
      vivo biological tissues. Together these results suggest the potential use of co
      ES hollow microfibers as tissue-mimicking phantoms in the field of medical
      imaging.

PMID- 23135106
TI  - [Effect of lipopolysaccharides extracted from Porphyromonas endodontalis on the
      expression of p38 and ERK1/2 in osteoblast].
AB  - PURPOSE: To investigate the effect of lipopolysaccharides (LPS) extracted from
      Porphyromonas endodontalis(P.e) on the expression of p38 and ERK1/2 in
      osteoblast. METHODS: MC3T3-E1 cells were stimulated with 10 MUg/mL P.e-LPS for
      0,5,15,30,60,180 min. The phosphorylation of p38 and ERK1/2 was measured by
      Western blot. Statistical analysis was performed using one- way ANOVA and Dunnett
      t test with SPSS11.0 software package. RESULTS: 10 MUg/mL LPS could significantly
      activate p38 MAPK. The peak of phosphorylated p38 was detected at 5 to 30
      min(P<0.01) and returned to baseline within 60 min; the level of phosphorylated
      ERK1/2 increased after the stimulation of LPS for 5 min and reached maximum at 15
      min (P<0.01) and declined after 30 min. CONCLUSIONS: P.e-LPS can induce the
      expression of p38 and ERK1/2 in osteoblast MC3T3-E1, which indicates that P.e-LPS
      may play an important role in osteoblast through p38 and ERK1/2.

PMID- 23135107
TI  - [Effect of Rhizoma Drynariae and Salvia on alveolar bone density of rats with
      orthodontic tooth movement].
AB  - PURPOSE: To detect and compare the effects of traditional Chinese drugs, Rhizoma
      Drynariae and Salvia, on the density of alveolar bones of rats through animal
      models for molar movement. METHODS: 72 female, 8-week-old SPF Wistar rats were
      selected to establish the animal models for orthodontic tooth movement. The rats
      were randomly divided into 3 groups: Rhizoma Drynariae group, Salvia group and
      normal saline(NS) group. Each group had 24 rats. Rhizoma Drynariae asperoides
      decoction (6 g/kg), Salvia decoction (6 g/kg) and 3 mL 0.9% NS were drenched
      daily to the rats in the Rhizoma Drynariae group, the Salvia group and the NS
      group, respectively. Stability of the appliances was checked every day and the
      applied force was raised by adjusting the springs every 7 days. The rats were
      executed in batch on the 7th, 14th, 21st, 28th day by removing the skulls. Then
      the movement distance of the first maxillary tooth and the alveolar bone density
      were measured. All statistical analysis was performed using SPSS 18.0 software
      package. RESULTS: Teeth movements in the Rhizoma Drynariae group and the Salvia
      group was greater than the NS group (P<0.05) while no significant difference
      (P>0.05) was found between the first two ones. Though alveolar bone density
      showed a trend to decrease in all 3 groups, the Rhizoma Drynariae and Salvia
      groups decreased slowly (P<0.05) and no significance was discovered between the
      two group (P>0.05). CONCLUSIONS: Rhizoma Drynariae and Salvia can both slow the
      alveolar bone density decrease and accelerate the orthodontic tooth movement.

PMID- 23135108
TI  - [The influence of COX-2 depressant in angiogenesis of oral squamous cell
      carcinoma].
AB  - PURPOSE: To investigate the COX-2 depressant on cell apoptosis and angiogenesis
      of oral squamous cell carcinoma. METHODS: RT-PCR and Western blotting were used
      to detect the effect of NS-398, the COX-2 inhibitor on mRNA and protein
      expression of VEGF and Survivin in oral squamous carcinoma cell line Tca8113.
      SPSS11.5 software package was used for statistical analysis. RESULTS: NS-398
      could down-regulate the expression of VEGF and Survivin in Tca8113 in a time
      dependent manner. CONCLUSIONS: NS-398 could down-regulate the expression of VEGF
      and survivin in Tca8113 and plays an important role in cell apoptosis and
      angiogenesis of oral squamous cell carcinoma.

PMID- 23135109
TI  - [Investigation of rat submandibular gland cells and antheraea pernyi silk fibroin
      films co-culture in vitro].
AB  - PURPOSE: In this study, the morphology, attachment, growth and secretion of rat
      submandibular gland cells (RSMGs) cultured on the antheraea pernyi silk
      fibroin(ApSF) films were observed in vitro. METHODS: RSMGs were seeded on ApSF
      scaffolds and bombyx mori silk fibroin (BmSF) scaffolds respectively. RSMGs which
      were seeded on tissue culture plastic were treated as a negative control group.
      With the method of immunocytochemistry (CK8 and amylase), the phenotype of cells
      were identified. The co-cultivation of RSMGs and two kinds of scaffolds were
      observed by using SEM and fluorescence microscopy. The adherence rate of cells
      attaching to each experimental material was estimated. MTT assay was performed to
      determine the proliferation of RSMGs cultured on different scaffolds. The
      secretion function of cultured cells was evaluated by assay of amylase activity.
      All the data was analyzed by SPSS13.0 software package. RESULTS: The
      immunohistochemical staining showed that the cultured epithelial cells of RSMGs
      were positive for the specific antibody of CK8 and the acinar cells were positive
      for the specific antibody of amylase. SEM showed that the cultured cells with
      microvillus anchored well to ApSF films and extended pseudopods to the scaffolds.
      Fluorescence microscopy showed that with the extension of incubation time, the
      amount of cells that attached to scaffolds increased. The attachment of RSMGs on
      ApSF films was almost the same as that on BmSF films after 1 h culture(P>0.05).
      The adherence rate of RSMGs on ApSF films was higher than that on BmSF films
      (post-seeding 4,8,12 h, P<0.05). There was no significant difference between ApSF
      group and BmSF group after 24 h culture (P>0.05), Proliferation of RSMGs cultured
      on ApSF films for 3 to 5 days was remarkable and that of RSMGs cultured on ApSF
      films for 7 days reached peak. The proliferation rate of RSMGs cultured on ApSF
      scaffolds was higher than that on BmSF scaffolds (post-seeding 3,5,7 d, P<0.05),
      ApSF group and BmSF group were higher than the negative control group (P<0.05).
      Amylase content of RSMGs cultured on ApSF films was higher than that on BmSF
      films (post-seeding 3,5,7 d, P<0.05) , ApSF group and BmSF group were higher than
      the negative control group (P<0.05). CONCLUSIONS: ApSF films can support RSMGs
      attachment, growth, secretion function maintenance and phenotypic maintenance;
      and has better biocompatibility for RSMGs in vitro culture.

PMID- 23135110
TI  - [Experimental study of osseointegration of nHA/BG coating and Bio-Oss in implant
      defects].
AB  - PURPOSE: To evaluate bone regeneration in defects at titanium implants with
      nHA/BG coating in conjunction with Bio-Oss. METHODS: Four mandibular premolars
      were extracted in 6 Beagle dogs. After 3 months, buccal dehiscence-type defects
      (2.25 mm*3 mm*4 mm) were surgically created following implant site. The three
      treatment modalities were randomly allocated: nHA/BG implant/Bio-Oss, nHA/BG
      implant/blood clot, and mHA implant/Bio-Oss. After 8 and 16 weeks, the dogs were
      sacrificed respectively. A histomorphometric analysis was performed. The data was
      analyzed with SPSS 13.0 software package for Student's t test and ANOVA. RESULTS:
      At 8- and 16-week, nHA/BG implant group revealed comparable mean BIC (30% to 18%
      versus 61% to 53%). However, mHA implant/Bio-Oss group revealed significantly
      lower mean BIC (21% versus 46%) values than nHA/BG implant/Bio-Oss group.A
      significant difference was observed for the mean BIC and RA values at 8-week
      between nHA/BG implant/Bio-Oss group and mHA implant/Bio-Oss group. CONCLUSIONS:
      It is concluded that the application of Bio-Oss graft did not seem to interfere
      with the nHA/BG coating activity, but ensured a stabilization of the newly formed
      bone for defects.

PMID- 23135111
TI  - [Effect of different orthodontic interproximal reduction methods on the enamel].
AB  - PURPOSE: To find a suitable interproximal enamel (IER) reduction method for
      clinical use by pH cycles in vitro. METHODS: 50 human premolars extracted for
      orthodontic reasons were collected for the experiment. After removal of the
      roots, the crowns were split vertically into two halves with wafer-thin wheel
      blade. Then the 100 samples were randomly divided into 5 groups, 20 samples for
      each group. The enamel in each group was reduced with different IER methods:
      group I, stripping strip; group II, stripping disk; group III, stripping strip
      with polishing system and 35% orthophosphoric acid; group IV, stripping disk with
      polishing system and 35% orthophosphoric acid; group V, no treatment control
      group. All the samples were treated with pH cycles in vitro for 30 days. The
      microhardness of enamel surface of all samples was detected by microhardness
      testing machine. The enamel surface morphology of microstructure was examined by
      scanning electron microscopy(SEM).The data was analyzed with SPSS13.0 software
      package. RESULTS: 1.ANOVA detected statistically significant differences between
      groups. The post SNK-q test showed that there was no significant difference
      between group I and group II, between group III and group IV(P>0.05); But there
      was significant difference between group I and group III, group I and group IV,
      group II and group III, group II and group IV(P<0.01). And there was significant
      difference between group I and group V, group II and group V, group III and group
      V, group IV and group V(P<0.05). 2.From naked eye and SEM, there was no distinct
      difference between the two chemical polishing groups, but better than the others.
      CONCLUSIONS: 1.There is no significant difference between strip and disk after
      IER. 2.Chemical polishing group is better than the others after IER. 3.The
      scratches of the enamel surface caused by IER are hardly repaired even after
      remineralization.

PMID- 23135112
TI  - [Analysis of the bacterium adhesions on the surface of PFM materials in vitro].
AB  - PURPOSE: With the observation of bacterial adhesion on the surface of the PFM and
      enamel, we analyzed the sequence of these adhesions and offer options for
      prevention of their occurrence. METHODS: The specimen made of PFM were polished
      step by step. Then they, along with the enamel were put into the liquid BHI
      culture medium containing Ua, Pg and An. After 6h, 12h and 24h the adhesive
      microbial amount in the culture medium was determined by counting formation unit.
      F test was used to analyze the results with SPSS 6.0 software package. RESULTS:
      Pg was found neither on the surface of specimen, nor in the liquid BHI culture
      medium; The value of Ua/An in the groups of PFM was less than that in the groups
      of enamel within 6 hours. And 12 hours later, the maximal increment of An was
      seen in the group of PFM. And there was no change in the groups of PFM and enamel
      during 12 and 24 hours. CONCLUSIONS: Pg was inhibited when these bacteria were
      cultured together. If we wish to prevent the adhesion of Ua and An, the first 12
      hours is the critical period for PFM. Given the result of the analysis, PFM is a
      good restoration.

PMID- 23135113
TI  - [Proteomics analysis of mandibles in type 2 diabetic rat].
AB  - PURPOSE: To investigate the differentially expressed proteins in mandible between
      normal rats, and type 2 diabetic rats. METHODS: Wistar rats and Goto-Kakizaki
      (GK) rats were selected as normal controls and experimental rats respectively.
      Weight and blood glucose were measured before sacrificed. The mandibles of each
      group were removed at the same time. After protein extraction, differentially
      expressed proteins were separated by two-dimensional gel electrophoresis (2-DE)
      and identified by MALDI-TOF/TOF. Statistical analysis was performed using SPSS
      15.0 software package. RESULTS: Blood glucose levels of the experimental group
      were significantly higher than that of the control group(P<0.05). The weights of 
      the two groups were not significantly different. 20 proteins were differentially
      expressed at least 3-fold between GK rats and Wistar rats. Of the 20 proteins, 5
      proteins were more than 20-fold different between the two groups. The 5 proteins
      fell into 3 functional categories as follows: metabolism, binding proteins, and
      signal transduction. CONCLUSIONS: The differentially expressed proteins of
      mandible between GK rats and Wistar rats may be new targets for investigating the
      mechanisms of the effect of type 2 diabetes on mandible.

PMID- 23135114
TI  - [The influence of active calcium ions solution on the ultrastructure of the
      enamel and cementum of extracted teeth and the evaluation of its cytotoxicity].
AB  - PURPOSE: To detect the effect of active calcium ions solution on the
      ultrastructure of enamel and cementum of the extracted teeth and observe the
      cytotoxicity of the solution on NIH3T3 cell through cell culture. METHODS: Active
      calcium ions solution composition was detected with a Quanta200FEG field emission
      scanning electron microscopy, and the ultrastructure of teeth enamel and cementum
      was observed before and after the application of calcium ions solution. After
      diluting the calcium ions solution, MTT assay method was used to observe the
      impact of active calcium ions solution of different concentrations on the NIH3T3
      cells growth. Based on cell relative growth rate, the cytotoxicity grade was
      rated. RESULTS: Active calcium ions solution was composed of calcium, carbon,
      oxygen, and chlorine. And there was no change in the enamel and cementum before
      and after soaking the teeth with active calcium ions solution. The maximum
      concentration of safe calcium ions solution on cytotoxicity grade was 0.344
      mg/mL. CONCLUSIONS: Active calcium ions solution can be used in the oral
      cavity,but appropriate concentration should be selected.

PMID- 23135115
TI  - [Finite element contact stress analysis of simulating teeth with wedge-shaped
      defects in the cervical region].
AB  - PURPOSE: To study the distribution of stress of simulating teeth with wedge
      shaped defects in the cervical region. METHODS: The models of anisotropic enamel
      of the mandibular first premolar and the opposite maxillary first premolar crown
      were created. A defect was introduced into the model of mandibular premolar in
      the buccal cervical region along the enamelo-dentinal junction. The stress
      distribution in the cervical region of the mandibular premolar was investigated
      with regard to different loading conditions simulating working, nonworking and
      vertical micromotions. In each case, the stroke was applied to the mandibular
      premolars in a stepping procedure using nonlinear contact analysis. RESULTS: The
      stresses were concentrated in the defect of the enamel and dentin at the enamelo
      dentinal junction(EDJ) in the condition of different loading, especially in the
      condition of simulating lateral excursion on one contact. CONCLUSION: Undermined
      cervical EDJ had a significant effect on the stress distribution in the buccal
      cervical region.

PMID- 23135116
TI  - [Expression of substance P and vascular endothelial growth factor in human normal
      and inflammatory dental pulps].
AB  - PURPOSE: To investigate the expression and relationship of substance P(SP) and
      vascular endothelial growth factor (VEGF) in human dental pulp under the normal
      and pathological conditions, so as to study their role in pulp microcirculation.
      METHONDS: Ten teeth extracted for orthodontic or impacted reason were chosen as
      normal group. Twenty-nine traumatic teeth from the same age group needing root
      canal therapy were divided to initial-stage trauma group, early-stage
      inflammation group, later-stage inflammation group. Immunohistochemical technique
      was applied to determine the expression and distribution of SP and VEGF in each
      group. The data was analyzed by one-way ANOVA and correlation analysis with
      SPSS13.0 software package. RESULTS: Compared with normal group,SP expression in
      other groups was significantly down-regulated(P<0.05). The VEGF expression in
      early-stage inflammation group was significantly up-regulated compared with the
      other groups (P<0.05), but down-regulated in later-stage inflammation group
      (P<0.05). The expression of SP and VEGF had negative correlation in different
      groups(r=-0.378,P<0.05). CONCLUSIONS: SP may induce the pulp microcirculation
      change by regulating VEGF, and participate in pulp neurogenic inflammation.

PMID- 23135117
TI  - [Application of computer-assisted navigation in oral and maxillofacial surgery:
      retrospective analysis of 104 consecutive cases].
AB  - PURPOSE: To evaluate the application of computer-assisted navigation system
      (CANS) in Oral and Maxillofacial Surgery. METHODS: One hundred and four patients
      were included in this study, including 34 with zygomatic-orbital-maxillary
      fracture, 27 with unilateral TMJ ankylosis, 29 with fibrous dysplasia, 9 with
      mandibular angle hypertropia, 3 with cartilage and bone tumors and 2 with facial
      foreign bodies. CT scan was performed and the data was saved as Dicom (digital
      imaging and communications in medicine) format. With preoperative planning and 3
      dimensional simulation, normal anatomic structures of the affected side were
      created by superimposing and mirroring the unaffected side. The osteotomy lines,
      amount and range of resection, the reduction position of bony segments and the
      reconstruction morphology was determined and displayed. All surgeries were
      performed under the guidance of navigation system. The accuracy of navigation was
      evaluated by comparing the postoperative CT three-dimensional model with
      preoperative surgical planning. RESULTS: Through registration, an accurate match
      between the intra-operative anatomy and the CT images was achieved. With the
      guidance of navigation, anatomic structures and the position of surgical
      instruments were shown real-time on the screen. No complications occurred in all
      patients and the systematic error was within 1 mm. Good coincidence with
      preoperative planning was achieved for osteotomy lines, the amount of resection
      and reduction of fractures. The mean error between virtual and real results was
      (1.46+/-0.24) mm. All patients healed uneventfully and facial symmetry was
      improved. CONCLUSIONS: With the ability of preoperative planning, surgical
      simulation and postoperative prediction, CANS shows its great value in improving
      the accuracy of oral and maxillofacial surgery, reducing trauma and restoring
      facial symmetry. It is regarded as a valuable and safe technique in this
      potentially complicated procedure.

PMID- 23135118
TI  - [Measurement of alveolar bone thickness of adult skeletal Class III patients in
      mandibular anterior region].
AB  - PURPOSE: To describe alveolar bone thickness in mandibular anterior region of
      skeletal Class III malocclusion with the help of Cone-beam CT. METHODS: The
      subjects were selected from consecutive adult patients seeking orthodontic
      treatment in Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong
      University School of Medicine from January 2008 to March 2011, which included 64
      patients diagnosed to be skeletal Class I malocclusion (Class I group) and 66
      patients diagnosed to be skeletal Class III malocclusion (Class III group). Both
      Class I and Class III groups were divided into 3 divisions respectively according
      to different vertical facial types. Mandibular left central incisor of each
      subject was chosen for measurement. The labial (L1), lingual (L2) and total
      (L0)alveolar bone thickness of skeletal Class III patients in mandibular anterior
      region were assessed using a CBCT analyzing method with Class I group as the
      control group. Data was processed with SAS8.02 software package. RESULTS:
      L1(P<0.05),L2(P<0.01) and L0(P<0.01) of Class III group were thinner than those
      of Class I group. L1 of high-angle Class III malocclusion was thinner than that
      of average-angle(P<0.01)and low-angle(P<0.01) ones ; L2 of average-angle Class
      III malocclusion was thinner than that of low-angle ones(P<0.01) and thicker than
      that of high-angle ones(P<0.05); L0 of low-angle Class III malocclusion was
      thicker than that of average-angle ones(P<0.01),which was thicker than that of
      high-angle ones(P<0.01). L1 of Class III group with different vertical facial
      types was thicker than L2(P<0.01). CONCLUSIONS: Skeletal Class III malocclusion
      exhibits thinner alveolus around the mandibular incisor apices compared with
      Class I malocclusion, which shows strong connection with different vertical
      facial types. Root apices of mandibular anterior teeth of skeletal Class III
      malocclusion situated closer to labial cortical bone than lingual cortical bone.
      It is necessary to access the alveolar bone thickness of adult skeletal Class III
      patients in mandibular anterior region before orthodontic camouflage or surgical
      orthodontic treatment. Orthodontic camouflage might not be a reasonable treatment
      alternative for these patients.

PMID- 23135119
TI  - [Expression of the activating receptor NKG2D on peripheral blood mononuclear
      cells in patient with oral squamous cell carcinoma and its clinical
      significance].
AB  - PURPOSE: To investigate the expression of activating receptor NKG2D(natural
      killer group 2,member D) on peripheral blood mononuclear cells(PBMCs) in patients
      with oral squamous cell carcinoma(OSCC) and its clinicopathological significance.
      METHODS: The expression of NKG2D on PBMCs in 54 OSCC patients and 20 healthy
      controls were assessed by flow cytometry. The data was analyzed with SPSS16.0
      software package for independent-sample t test and one-way ANOVA test. RESULTS:
      The positive rate of assay for NKG2D on PBMCs in OSCC patients (12.49+/-5.26)%
      was lower than that of the controls (22.93+/-8.14)% (P<0.05). And which was
      significantly different among different clinicopathological parameters such as
      tumor size and disease stage(P<0.05), but no significant difference was found
      among different gender, age, tumor location, tumor differentiation and cervical
      lymph node status (P>0.05). CONCLUSIONS: The NKG2D expression on PBMCs in OSCC
      patients was lower than that of healthy controls and was correlated with tumor
      size and disease stage.

PMID- 23135120
TI  - [Study of alphaB-crystallin and its possible role of anti-apoptosis in oral
      verrucous carcinoma].
AB  - PURPOSE: To investigate the expression of alphaB-crystallin and its possible role
      of anti-apoptosis in oral verrucous carcinoma. METHODS: The expression of alphaB
      crystallin and activated caspase-3 was detected in oral verrucous carcinoma, oral
      squamous carcinoma and normal mucosa by immunohistochemistry, and their
      relationship was investigated. SPSS 16.0 software package was used for
      statistical analysis. Nonparametric test and spearman correlation test were
      performed. RESULTS: The expression of alphaB-crystallin in oral verrucous
      carcinoma and oral squamous carcinoma was significantly higher than that in
      normal mucosa(P<0.05). And in oral verrucous carcinoma, the increase of
      expression of alphaB-crystallin coincided with the decrease of expression of
      activated caspase-3(P<0.05). CONCLUSION: alphaB-crystallin may play a role of
      anti-apoptosis by inhibiting the activation of caspase-3 in oral verrucous
      carcinoma.

PMID- 23135121
TI  - [Study on relationship between expression of podoplanin and lymph node metastasis
      in oral squamous cell carcinoma].
AB  - PURPOSE: In oral squamous cell carcinoma(OSCC) and normal oral tissues,
      podoplanin was used to mark lymphatic tract and recorded the lymphatic vessel
      density (LVD) by corresponding tissue. The aim of this study was to evaluate LVD
      in correlation with lymphnode metastases in patients with OSCC. METHODS: The
      expressions of VEGF-C antibodies and anti-podoplanin were detected in 21 normal
      oral tissues and 88 paraffin sections of OSCC by immunohistochemistry(S-P);
      Determination of LVD (assessed by immunostaining for podoplanin) was performed as
      suggested by Weidner, the numerical value expressed by x+/-s Intratumoral
      lymphatic vessels (I-LVD) and peritumoral lymphatic vessels (P-LVD) were
      assessed, respectively. Data was analyzed with SPSS 13.0 software package and t
      test was used for comparative analysis of LVD between normal oral tissues and
      OSCC tissue and LVD (including P-LVD and ILVD) of the lymph node metastasis and
      without lymph node metastasis. RESULTS: There was significant difference between
      LVD of normal control tissues, peritumoral and intratumoral tissues.The
      intratumoral lymphatic vessels (ILVD) were small and collapsed, while the
      peritumoral ones were large and dilated. The PLVD's density with lymph node
      metastasis(14.270+/-4.610) was significantly higher than that without lymph node
      metastasis (9.450+/-2.411, P<0.05). CONCLUSION: The results indicated that
      peritumoral lymphangiogenesis may have an important impact on lymph node
      metastasis in OSCC.

PMID- 23135122
TI  - [The application of cone-beam computed tomography in diagnosing the lesions of
      apical periodontitis of posterior teeth].
AB  - PURPOSE: To evaluate the effect of periapical radiography in diagnosing the
      lesions of the apical periodontitis (AP) of posterior teeth, with CBCT imaging as
      a standard. METHODS: One hundred and six posterior teeth in 80 patients were
      examined by periapical radiography and CBCT, which consisted of healthy teeth (58
      teeth), chronic pulpitis (11 teeth), chronic apical periodontitis (34 teeth),
      remnant teeth with normal apical images after root canal therapy (3 teeth). All
      images were measured and evaluated by two experienced dentists by using
      periapical index (PAI) to ensure the classifications. The results were analyzed
      statistically with SPSS 13.0 software package for chi2 test. RESULTS: AP was
      identified in 39.6% and 59.4% of 106 cases by radiography and CBCT, the
      difference was significant (chi2=8.32, P<0.01). The use of conventional
      radiography for detection of AP should be done with care because of the great
      possibility of artifacts which might lead to misdiagnosis. Because of its
      accuracy, CBCT is more useful for clinic diagnosis and therapy. Furthermore, the
      images of CBCT could show destruction of cortical bone that couldn't detect by
      periapical radiography. CONCLUSIONS: CBCT is more accurate than periapical
      radiography for AP diagnosis. CBCT can reveal the details of the lesions and
      adjacent structures and provide correct clinical diagnosis and scientific
      treatment planning with accurate evidence.

PMID- 23135123
TI  - [Meta analysis of association between TNF-alpha-308 polymorphism and
      periodontitis in Chinese Han population].
AB  - PURPOSE: To assess the association between TNF-alpha-308 polymorphism and
      periodontitis in Chinese Han population. METHODS: Articles published between 1994
      and 2011 were searched in the fulltext database of CNKI, Chinese Biomedical
      Literature Database, Wanfang Database and PubMed. Case-control studies on TNF
      alpha-308 polymorphism and periodontitis were searched up to Feb.,2011, including
      articles in Chinese and in English. Meta analysis was performed to evaluate the
      prevalence of Allele 2 between case group and control group. RESULTS: Five
      studies were entered into Meta analysis,with 494 cases and 501 controls . No
      significant heterogeneity was found among the studies(P=0.38); the pooled OR
      value of allele 2 was 2.12(95% CI 1.57-2.86), with significant
      difference(P<0.01). CONCLUSION: Meta analysis showed that TNF-alpha-308
      polymorphism was associated with periodontitis in Chinese Han population.

PMID- 23135124
TI  - [Analysis of caries status among 5-year-old children in Shanghai from 2008 to
      2011].
AB  - PURPOSE: To analyze the status of 5-year-old children's oral caries in Shanghai
      from 2008 to 2011, and to provide information to evaluate oral health status and
      improve service level. METHODS: By using equal-sized randomly sampling method,
      this survey was carried out on the caries status of randomly selected 950
      children aged 5 years in Shanghai respectively in 2008 and 2009, and 900 children
      respectively in 2010 and 2011. The data of prevalence of dental caries, dmft,
      caries filling constituent ratio and SiC index were collected. Statistical
      analysis was performed using SPSS 13.0 software package by means of independent
      samples t test, one way ANOVA and Chi-square test. RESULTS: From 2008 to 2011,
      the prevalence of deciduous tooth caries among 5-year-old children was 63.47%,
      64.00%, 64.89% and 64.44%, respectively. The mean dmft score was 2.96, 2.99, 3.23
      and 3.09, respectively. The caries filling ratio was 10.93%, 12.76%, 16.96% and
      20.63%, respectively. The SiC index was 7.10, 7.20, 7.74 and 7.37, respectively.
      The prevalence of caries and mean dmft showed no significant difference in four
      years(P>0.05), and the caries filling constituent ratio was remarkably increased
      (P<0.01). The SiC index was two times higher than dmft. Each year the prevalence
      of deciduous tooth caries and mean dmft in urban areas were lower than in
      suburban areas (P<0.01), but the children came from urban areas showed
      significant higher filling rate than those from suburban areas (P<0.01).
      Deciduous tooth caries were concentrated in one-third of children. CONCLUSIONS:
      The prevalence of deciduous tooth caries and dmft of 5-year-old children in
      Shanghai changed little, and the caries filling constituent ratio has increased
      year by year. To promote children's oral health further, we still need to take
      more active preventive measures for high caries risk group.

PMID- 23135125
TI  - [Clinical study of the proportion of salivary gland tumors in the elder
      patients].
AB  - PURPOSE: To investigate the proportion of salivary gland tumors in the elder
      patients in the past ten years, in order to provide reference for clinical
      diagnosis and treatment. METHODS: The medical data of salivary gland tumors
      treated in our department from January 2000 to December 2009 were reviewed and
      analyzed. The changes of three periods between 21c10s, 20c90s and 20c80s were
      compared. RESULTS: The number of salivary gland tumors in elder patients
      increased rapidly in recent years, especially that of benign tumors. Warthin's
      tumor was the most common benign tumors, and adenoid cystic carcinoma was most
      often found in malignant tumors. Carcinoma ex pleomorphic adenoma rose to the
      third among malignant tumors of salivary gland and first among parotid gland
      malignancies. The proportion of benign tumor was almost equal to malignant tumor
      in minor salivary gland. The benign-malignant ratio of palatal salivary gland was
      1.34:1, which was opposite to the previous figure. The parotid gland was the most
      common site, followed by palatal and submandibular gland. CONCLUSIONS: The
      proportion of salivary gland tumors in elder patients in 2000s was different from
      that in 1980s and 1990s. The changes should be taken into attention in daily
      clinical works.

PMID- 23135126
TI  - [Comparative study on the apical root resorption between self-ligating and
      conventional brackets in extraction patients].
AB  - PURPOSE: To explore whether orthodontic light force with self-ligating brackets
      can reduce the amount of external apical root resorption (EARR). METHODS: Thirty
      patients with Class I or II crowding malocclusion were selected. Four first
      premolars of all patients were extracted in orthodontic treatment. 15 patients
      were treated with self-ligating brackets (Damon 3MX) and 15 patients with
      conventional ligation brackets, respectively. Patients in two groups were
      comparable in gender, age, crowded degree and malocclusion classification at the
      commencement of treatment. EARR of the maxillary and mandible incisors was
      evaluated on panoramic radiographs and models taken before and after treatment,
      and measured in millimeters. Student's t test was performed using SPSS19.0
      software package. RESULTS: Overall, no difference was found in the amount of EARR
      between the two groups. The amount of EARR in maxillary central incisor was
      (2.05+/-1.51) mm in Damon group and (2.08+/-1.21) mm in conventional
      group(P=0.973>0.05); (1.77+/-1.01) mm in maxillary lateral incisor in Damon group
      and (1.91+/-1.59) mm in conventional group(P=0.848>0.05); (2.06+/-1.62) mm in
      mandibular central incisor in Damon group and (1.98+/-1.50) mm in conventional
      group(P=0.926>0.05); (1.94+/-1.45) mm in mandibular lateral incisor in Damon
      group and (1.84+/-1.17) mm in conventional group(P=0.888>0.05). CONCLUSION: No
      difference should be expected for root resorption between self-ligating and
      conventional brackets in orthodontic extraction treatment.

PMID- 23135127
TI  - [Treatment of primary trigeminal neuralgia with radiofrequency thermocoagulation:
      report of 648 consecutive cases].
AB  - PURPOSE: To analyze the clinical efficacy of radiofrequency thermocoagulation in
      the treatment of idiopathic trigeminal neuralgia, and discuss the method, skill
      of radiofrequency thermocoagulation and complications. METHODS: 648 patients with
      idiopathic trigeminal neuralgia , who were treated  by radiofrequency
      thermocoagulation via foramen infraorbitale approach, lateral approach, anterior
      approach and other approach from July 2001 to March 2011 in our hospital, were
      observed and the clinical efficacy was evaluated. RESULTS: After the first
      treatment of the 648 patients, the rate of pain control was 98.3% via foramen
      infraorbitale approach, 91.0% via lateral approach and 95.5% via former approach.
      The overall response rate was 96.0%. 395 patients were followed up from 6 months
      to 2 years. The recurrent rate within one year was 9.6%, 20.5% within two years.
      Good response was achieved after re-treatment with radiofrequency
      thermocoagulation in recurrent patients. CONCLUSIONS: The clinical efficacy of
      radiofrequency thermocoagulation in the treatment of idiopathic trigeminal
      neuralgia is good and reliable. The operation is simple, the indication is wide,
      and the complication is fewer. CT location can improve the accuracy of puncture,
      and reduce complications.

PMID- 23135128
TI  - [Evaluation of masticatory efficiency of lingualized occlusal complete denture].
AB  - PURPOSE: To compare the masticatory efficiency of lingualized occlusal complete
      denture with that of semi-anatomical occlusal complete denture. METHODS: Sixty
      cases with flat or depressed residual ridges were selected from 2009 to 2011.
      After randomly divided into two groups, the patients were treated with
      lingualized and semi-anatomical occlusal complete dentures, respectively. A
      comparative study of masticatory efficiency was carried out on patients wearing
      lingualized occlusal complete dentures with those wearing semi-anatomical
      occlusal complete dentures in different period (1st, 2nd, 3rd, 6th month) after
      wearing. SAS6.16 software package was used for data analysis. RESULTS: Once
      masticatory time or masticatory times were fixed, there was no significant
      difference between lingualized occlusal dentures and semi-anatomical occlusal
      complete dentures (P>0.05). CONCLUSION: Lingualized occlusal complete denture can
      achieve good masticatory efficiency for edentulous patients with flat or
      depressed residual ridges.

PMID- 23135129
TI  - [Effect of doctor-patient communication education on oral clinical practice].
AB  - PURPOSE: To evaluate the effect of doctor-patient communication education on
      dental clinical practice. METHODS: The process of 61 dental interns' clinical
      practice was divided into two stages. The dental interns were taught with
      traditional teaching method in the first stage. Doctor-patient communication and
      communication skill training were added to the second stage. Scale of medical
      student's doctor-patient communication behavior was used to evaluate the dental
      interns' behavior by themselves after two stages. The SEGUE frame work was used
      to evaluate the dental interns' behavior by teachers after two stages. All
      statistical analysis was performed using SPSS 13.0 software package. The result
      of scale of medical student's doctor-patient communication behavior was analyzed
      using Fisher exact test or Chi-square test. The score of the SEGUE frame work was
      analyzed using Student's t test. RESULTS: The result of Scale of medical
      student's doctor-patient communication behavior showed only 37.71% of dental
      interns could establish good doctor-patient relationship in the first stage.
      After doctor-patient communication and communication skill training, the
      percentage became 75.4%. The result of the SEGUE frame work showed the score was
      raised from 16.066+/-3.308 to 21.867+/-2.456, and a significant difference was
      found between the two stages. CONCLUSIONS: Doctor-Patient communication education
      can improve dental interns' communication skills and help to establish a good
      doctor-patient relationship.

PMID- 23135130
TI  - [Xeroderma pigmentosum with repeated facial skin carcinogenesis: report of one
      case].
AB  - Xeroderma pigmentosum is a relatively rare pigment atrophic autosomal recessive
      genetic disease, mainly due to defect of DNA excision repair capacity, resulting
      in ineffective removal of UV-induced pyrimidine dimers, and finally cell damage.
      This paper reported a case of xeroderma pigmentosum with recurrent episodes of
      oral and maxillofacial carcinogenesis, and discussed the etiology, pathology,
      clinical characteristics, classification, diagnosis and treatment methods of
      Xeroderma pigmentosum.

PMID- 23135131
TI  - Single-molecule magnet based on a C-type polyoxomolybdate with an S = 11 ground
      state: [Fe5CoMo22As2O85(H2O)]15-.
AB  - A C-type polyoxomolybdate containing a mixed-transition metal cluster Fe(5)Co has
      been prepared as an ammonium salt,
      (NH(4))(15)[Fe(5)CoMo(22)As(2)O(85)(H(2)O)].15H(2)O (1). Interestingly, the
      magnetism measurements show that the compound exhibits not only an overall
      ferromagnetic cluster with a large spin ground state of S = 11 but also the
      behavior of single-molecule magnets.

PMID- 23135132
TI  - HPLC determination of phenolic acids, flavonoids and juglone in walnut leaves.
AB  - A high-performance liquid chromatographic method with gradient elution and diode
      array detection was developed to quantify free phenolic acids (gallic, vanillic,
      chlorogenic, caffeic, syringic, p-coumaric, ferulic, sinapic, salycilic, elagic
      and trans-cinnamic), flavonoids (catechin, epicatechin, rutin, myricetin and
      quercetin) and juglone in walnut leaves. Chromatographic separation was performed
      on a Hypersil Gold C18 column (5 um particle size, 250 * 4.6 mm) and detection
      was conducted at three different wavelengths (254, 278 and 300 nm) according to
      the absorption maxima of the analyzed compounds. Validation procedures were
      conducted and the method was proven to be precise, accurate and sensitive. The
      developed method has been applied to analyze walnut leaves samples from nine
      different cultivars, with the same agricultural, geographical and climatic
      conditions. The experimental results revealed high concentrations of myricetin,
      catechin hydrate and rutin, and low concentrations of quercetin and epicatechin
      aglycones. Ellagic acid was established as the dominating phenolic acid of walnut
      leaves, followed by trans-cinnamic, chlorogenic and caffeic acids. Juglone
      content varied between 44.55 and 205.12 mg/100 g fresh weight. Significant
      differences were detected among cultivars for the concentration levels of
      phenolics. 

PMID- 23135133
TI  - Determination of 2-aryl-7(3',4'-dialkoxyphenyl)-pyrazolo [1,5-alpha] pyrimidine,
      a novel phosphodiesterase-4 inhibitor, in rat plasma by liquid chromatography
      tandem mass spectrometry.
AB  - A method for assaying a novel phosphodiesterase-4 inhibitor, 2-aryl-7(3',4'
      dialkoxyphenyl)-pyrazolo [1,5-alpha] pyrimidine (PDE-310), was developed and
      validated in rat plasma using liquid chromatography-tandem mass spectrometry (LC
      MS-MS). Rat plasma samples were processed by liquid-liquid extraction with ethyl
      acetate and injected onto the LC-MS-MS system for quantification. PDE-310 and
      imipramine (i.e., internal standard) were separated using a Gemini C18 column
      with mixture of acetonitrile and 0.1% formic acid (70:30, v/v) as the mobile
      phase. The ion transitions monitored were m/z 425.0 -> 331.0 for PDE-310 and m/z
      281.3 -> 86.1 for imipramine in the multiple-reaction monitoring mode. The
      detector response was specific and linear for PDE-310 concentrations in the range
      of 0.1-50 ug/mL. The intra-day and inter-day precision and accuracy of the method
      were determined to be within the acceptance criteria for assay validation
      guidelines. The recoveries were approximately 85.7 and 88.2% from rat plasma for
      PDE-310 and imipramine, respectively. PDE-310 was stable under various processing
      and handling conditions. PDE-310 concentrations were readily measured in rat
      plasma samples up to 8 h after an intravenous administration of PDE-310,
      suggesting that the assay is practically useful.

PMID- 23135134
TI  - Administration of heat shock protein 65 inhibits murine melanoma growth in vivo.
AB  - The association between heat shock protein (HSP) 65 and immune diseases has been
      investigated for many years. The aim of this study was to explore the antitumor
      effects and possible antitumor mechanism of HSP65. Mice were immunized with HSP65
      via subcutaneous injection. Specific IgG antibodies against HSP65 were detected
      in the sera of immunized mice by enzyme-linked immunosorbent assay and verified
      by western blot analysis. HSP65 effectively inhibited the growth of tumors as
      well as both the protective and therapeutic antitumor immunities in the melanoma
      tumor models of mice and prolonged the survival of the tumor-bearing mice.
      Furthermore, HSP65 also attenuated tumor-induced angiogenesis in the intradermal
      model and pulmonary metastasis in the tail intravenously injected model of mice.
      It was demonstrated that the administration of HSP65 is able to effectively
      inhibit the growth, angiogenesis and metastasis of murine melanoma in vivo and
      provide new prospects for the immunotherapy of melanoma. 

PMID- 23135135
TI  - Potential influence of plant chemicals on infectivity of Batrachochytrium
      dendrobatidis.
AB  - We explored whether extracts of trees frequently found associated with amphibian
      habitats in Australia and Arizona, USA, may be inhibitory to the fungal pathogen
      Batrachochytrium dendrobatidis (Bd), which has been associated with global
      amphibian declines. We used salamanders Ambystoma tigrinum as the model system.
      Salamanders acquired significantly lower loads of Bd when exposed on leaves and
      extracts from the river red gum Eucalyptus camaldulensis, and loads were also low
      in some animals exposed on extracts of 2 oak species, Quercus emoryi and Q.
      turbinella. Some previously infected salamanders had their pathogen loads
      reduced, and some were fully cured, by placing them in leaf extracts, although
      some animals also self cured when housed in water alone. A significant number of
      animals cured of Bd infections 6 mo earlier were found to be resistant to
      reinfection. These results suggest that plants associated with amphibian habitats
      should be taken into consideration when explaining the prevalence of Bd in these
      habitats and that some amphibians may acquire resistance to the fungus if
      previously cured.

PMID- 23135136
TI  - Clinical trials with itraconazole as a treatment for chytrid fungal infections in
      amphibians.
AB  - Due in large part to recent global declines and extinctions, amphibians are the
      most threatened vertebrate group. Captive assurance colonies may be the only
      lifeline for some rapidly disappearing species. Maintaining these colonies free
      of disease represents a challenge to effective amphibian conservation. The fungal
      disease chytridiomycosis, caused by the fungus Batrachochytrium dendrobatidis
      (Bd), is one of the major contributors to global amphibian declines and also
      poses a serious threat to captive assurance colonies. Many treatment options for
      Bd infection have not been experimentally tested and the commonly administered
      dosages of some drugs are known to have negative side effects, highlighting a
      need for clinical trials. The objective of this study was to clinically test the
      drug itraconazole as a method for curing Bd infection. We bathed Bd-positive
      juveniles of 2 anuran amphibian species, Litoria caerulea and Incilius nebulifer,
      in aqueous itraconazole, varying the concentration and duration of treatment, to
      find the combination that caused the fewest side effects while also reliably
      ridding animals of Bd. Our results suggest that a bath in 0.0025% itraconazole
      for 5 min d-1 for 6 d reliably cures Bd infection and causes fewer side effects
      than the longer treatment times and higher concentrations of this drug that are
      commonly administered.

PMID- 23135137
TI  - Genetically similar VHSV isolates are differentially virulent in olive flounder
      Paralichthys olivaceus.
AB  - Two viral hemorrhagic septicemia virus (VHSV) isolates, VHSV-KR-CJA and VHSV-KR
      YGH, were isolated from viral hemorrhagic septicemia disease outbreaks in
      flounder farms in South Korea. The VHSV-KR-CJA isolate was isolated from a
      flounder farm with high mortality (80%), while the VHSV-KR-YGH isolate was
      isolated from a flounder farm with low mortality (15%), suggesting that these
      isolates differ in virulence. The virulence of these isolates was evaluated in
      juvenile flounder via intraperitoneal injection. Consistent with their virulence
      in the field, mortality data revealed that the VHSV-KR-CJA isolate was highly
      pathogenic (cumulative mortality of 80%), while the VHSV-KR-YGH isolate was less
      pathogenic in flounder (cumulative mortality of 20%). To characterize the
      genotypes of these viruses, the full open reading frames (ORFs) encoding
      nucleoprotein N, phosphoprotein P, matrix protein M, glycoprotein G,
      nonstructural viral protein NV, and polymerase L of these viruses were sequenced
      and analyzed. Sequence analysis revealed that both isolates are genetically very
      similar (identical amino acid sequences for P, M, NV, and L and >99.7 and 99.8%
      amino acid sequence identity for N and G, respectively). Phylogenetic analysis
      indicated that both of these viruses belong to the Genotype IVa group, suggesting
      that they originated from a common ancestral virus. The low pathogenicity VHSV
      strain may potentially evolve to become a more pathogenic strain through only a
      few nucleotide substitutions. Further functional analyses of mutations in VHSV
      genes are necessary to identify factors that determine VHSV pathogenicity in
      flounder.

PMID- 23135138
TI  - Reproducible challenge model to investigate the virulence of Flavobacterium
      columnare genomovars in rainbow trout Oncorhynchus mykiss.
AB  - Flavobacterium columnare is a Gram-negative bacterium that causes columnaris
      disease and has significant economic impacts on aquaculture production worldwide.
      Molecular analyses have demonstrated that there is genetic diversity among F.
      columnare isolates. A review of the published literature that used restriction
      fragment length polymorphism analysis of the 16S rRNA gene revealed that all
      isolates typed from salmonids were Genomovar I. Our objective was to develop a
      laboratory challenge model for F. columnare in rainbow trout Oncorhynchus mykiss
      (Walbaum) and use the model to determine the virulence of Genomovar I and II
      isolates. Six F. columnare isolates were obtained from rainbow trout experiencing
      losses due to columnaris disease and were determined to be Genomovar I. Three of
      these were chosen for a preliminary assessment of virulence, and isolate 051-10
      S5 was chosen for additional experiments to determine the reproducibility of the
      waterborne challenge model. In 2 independent experiments, cumulative percent
      mortalities (CPM) were 49 +/- 10% and 50 +/- 19%. Challenge of rainbow trout with
      Genomovar I and II isolates demonstrated a difference in the CPM, with the
      Genomovar II isolates inducing significantly higher CPM. This reproducible
      waterborne challenge model for columnaris disease in rainbow trout will be useful
      to investigate host-pathogen interactions, vaccine development, and other
      potential control strategies. This research also provides a basis for further
      defining the molecular diversity and virulence associated with F. columnare
      genomovars in rainbow trout and other salmonid species.

PMID- 23135139
TI  - Infection dynamics of Kudoa yasunagai (Myxozoa: Multivalvulida) infecting brain
      of cultured yellowtail Seriola quinqueradiata in Japan.
AB  - We monitored infection by a brain-infecting myxozoan Kudoa yasunagai in hatchery
      reared juvenile yellowtail Seriola quinqueradiata at a culturing site in Japan.
      Infection was detected by PCR and microscopic observation once every 1 to 4 wk
      during 2010 and 2011. In both years, we detected first infection in mid-July by
      PCR. Prevalence increased rapidly after the onset of infection, peaking at 100%
      within 4 wk. Parasites required less than 10 d to reach the brain after invasion.
      Development of plasmodia and formation of cysts took 4 to 8 wk. Infection did not
      reach a plateau and number of cysts tended to decline over time, suggesting
      possible recovery from the infection. A drastic decline in infection prevalence
      was observed during the season of highest water temperature (>30 degrees C) in
      2010. To understand this phenomenon, we conducted a laboratory experiment to
      compare infection prevalence and cyst formation in fish kept at 25 degrees C and
      30 degrees C. However, we could not detect obvious differences between the
      treatment groups during the 4 wk of the experiment. There was no apparent
      pathology associated with the infection. These results suggest that pathological
      effects of K. yasunagai may differ between fish species or that other factors are
      important in the development of infectious signs.

PMID- 23135140
TI  - Prevalence of Anguillicoloides crassus and growth variation in migrant yellow
      phase American eels of the upper Potomac River drainage.
AB  - Prevalence of the non-native swim bladder nematode Anguillicoloides crassus has
      recently increased in American eels from estuaries of the North American Atlantic
      coast, but little is known about parasite prevalence or conditions of previous
      infection in upstream migrant eels within upper watersheds. This study is the
      first to confirm presence of A. crassus in the upper Potomac River watershed. We
      estimated A. crassus prevalence during 3 time periods: September to October 2006
      (5/143 eels, 3.5%), August to October 2007 (0/49 eels), and June 2008 (0/50
      eels). All eels were sampled from the Millville Dam eel ladder on the lower
      Shenandoah River, a Potomac River tributary located approximately 285 km upstream
      of Chesapeake Bay, USA. Of the 5 infected eels, parasite intensity was 1 for each
      eel, and mean intensity was also 1.0. A swim bladder degenerative index (SDI) was
      calculated for the 50 eels from the final sampling period, and 38% of those eels
      (19 of 50) showed signs of previous infection by A. crassus. We also aged 42 of
      the 50 eels (mean +/- SE = 6.7 +/- 0.29 yr, range 4 to 11 yr) from the final
      sampling period. Based on the range of possible SDI scores (0 to 6), severity of
      previously infected swim bladders was moderate (SDI = 1 or 2). Previously
      infected eels, however, had a lower length-at-age than that of uninfected eels.
      Female yellow-phase eels in upper watersheds develop into large highly fecund
      silver-phase adults; hence, a parasite-induced effect on growth of yellow-phase
      eels could ultimately reduce reproductive potential.

PMID- 23135141
TI  - Disseminated toxoplasmosis in Antillean manatees Trichechus manatus manatus from
      Puerto Rico.
AB  - Necropsies were conducted on 4 Antillean manatees Trichechus manatus manatus that
      were stranded in single events on the coastal beaches of Puerto Rico from August
      2010 to August 2011. Three manatees were emaciated and the gastrointestinal
      tracts were devoid of digesta. Microscopically, all manatees had severe
      widespread inflammatory lesions of the gastrointestinal tract and heart with
      intralesional tachyzoites consistent with Toxoplasma gondii identified by
      histological, ultrastructural and immunohistochemical techniques. The
      gastrointestinal lesions included severe, multifocal to diffuse, chronic-active
      enteritis, colitis and/or gastritis often with associated ulceration, necrosis
      and hemorrhage. Enteric leiomyositis was severe and locally extensive in all
      cases and associated with the most frequently observed intralesional protozoans.
      Moderate to severe, multifocal, chronic to chronic-active, necrotizing
      myocarditis was also present in all cases. Additionally, less consistent
      inflammatory lesions occurred in the liver, lung and a mesenteric lymph node and
      were associated with fewer tachyzoites. Sera (n = 30) collected from free-ranging
      and captive Puerto Rican manatees and a rehabilitated/released Puerto Rican
      manatee from 2003 to 2012 were tested for antibodies for T. gondii. A positive T.
      gondii antibody titer was found in 2004 in 1 (3%) of the free-ranging cases
      tested. Disease caused by T. gondii is rare in manatees. This is the first report
      of toxoplasmosis in Antillean manatees from Puerto Rico. Additionally, these are
      the first reported cases of disseminated toxoplasmosis in any sirenian. The
      documentation of 4 cases of toxoplasmosis within one year and the extremely low
      seroprevalence to T. gondii suggest that toxoplasmosis may be an emerging disease
      in Antillean manatees from Puerto Rico.

PMID- 23135142
TI  - Skeletal abnormalities in humpback whales Megaptera novaeangliae stranded in the
      Brazilian breeding ground.
AB  - Skeletal tissues of 49 humpback whales Megaptera novaeangliae that stranded
      between 2002 and 2011 along the Abrolhos Bank seashore and its adjacent waters in
      Brazil were studied. Twelve (24.5%) animals presented pathological changes in one
      or more bones. Degenerative changes and developmental malformations were most
      frequent (10.2% each), followed by inflammatory/infectious and traumatic lesions
      (8.2% each). Infectious diseases led to severe lesions of the caudal vertebrae of
      2 whales. In one of these individuals, the lesions involved 6 caudal vertebrae,
      leading to ankylosis of 3 vertebrae. Degenerative changes were observed in the
      vertebral columns of 3 animals, involving the joints of 13 ribs of 1 individual,
      and in the humerus of 1 whale. Traumatic lesions, such as osseous callus in the
      ribs, were observed in 4 animals. In 1 whale, the rib showed severe
      osteomyelitis, possibly resulting from the infection of multiple fractures.
      Developmental abnormalities such as spina bifida on 3 cervical vertebrae of 1
      whale, fusion of spinal processes on thoracic vertebrae of 1 individual and
      fusion of the first 2 ribs unilaterally or bilaterally in 4 animals were found.
      Chronic infectious conditions found in the axial skeleton may have restrained
      spinal mobility and had detrimental effects on the general health of the animals,
      contributing to stranding and death. To our knowledge, this is the first
      systematic study on skeletal lesions in stranded humpback whales.

PMID- 23135143
TI  - First report of coral diseases in the Republic of Maldives.
AB  - Little is known about coral diseases in the Indian Ocean region, especially in
      the Republic of Maldives. This study aimed at documenting the presence of coral
      diseases in the archipelago of the Maldives. Surveys for lesions in
      scleractinians conducted at 8 sites around Magoodhoo Island (Faafu Atoll) in
      October and November 2010 led to the identification of 5 coral diseases and 1
      anomalous pigmentation response affecting 8 hard coral genera. White syndrome,
      skeleton-eroding band disease, black band disease, and Porites dark discoloration
      response were the most commonly observed conditions. In contrast with several
      reports of other reef systems, the overall observed prevalence of coral diseases
      was rather low (<2%), with individual prevalence ranging from 0.7% for skeleton
      eroding band to 0.18% for Porites dark discoloration response. These data
      represent the first report of coral diseases for the Republic of Maldives.

PMID- 23135144
TI  - Effects of high salinity, high temperature and pH on capsid structure of white
      spot syndrome virus.
AB  - The structural stability of white spot syndrome virus (WSSV) capsids at high
      salinity, high temperature and various pH values was studied. To obtain the viral
      capsids, the nucleocapsids were treated with high salinity. The results showed
      that high salinity treatment can cause the dissociation of VP15 and most of VP95
      from the nucleocapsid, but there were no noticeable alterations in morphology and
      ultrastructure of the nucleocapsid and capsid. The capsids retained morphological
      integrity at temperatures <45 degrees C but became aberrant at >60 degrees C. In
      addition, the capsids were relatively resistant to strong acid conditions and
      were tolerant to a broad pH range of 1 to 10. However, morphological change
      occurred at pH 10.5. The capsids broke up into small pieces at pH 11 and
      completely degraded in 0.1 and 1.0 M NaOH. These results indicated that the WSSV
      capsid is acid-stable and alkali-labile.

PMID- 23135145
TI  - Two-dimensional real-time blood flow and temperature of soft tissue around
      maxillary anterior implants.
AB  - PURPOSE: The aims of this study were to (1) evaluate the basic nature of soft
      tissue surrounding maxillary anterior implants by simultaneous measurements of
      blood flow and surface temperature and (2) analyze differences with and without
      bone grafting associated with implant placement to try to detect the signs of
      surface morphology change. MATERIALS AND METHODS: Twenty maxillary anterior
      implant patients, 10 bone grafting and 10 graftless, were involved in this
      clinical trial. Soft tissue around the implant was evaluated with 2-dimensional
      laser speckle imaging and a thermograph. RESULTS: Blood flow was significantly
      lower in attached gingiva surrounding implants in graftless patients (P =
      0.0468). On the other hand, it was significantly lower in dental papillae (P =
      0.0254), free gingiva (P = 0.0198), and attached gingiva (P = 0.00805) in bone
      graft patients. Temperature was significantly higher in free gingiva (P =
      0.00819) and attached gingiva (P = 0.00593) in graftless patients, whereas it was
      significantly higher in dental papilla and free gingiva in implants with bone
      grafting. CONCLUSION: The results suggest that simultaneous measurements of soft
      tissue blood flow and temperature is a useful technique to evaluate the
      microcirculation of soft tissue surrounding implants.

PMID- 23135146
TI  - Professional media as opposed to social media.

PMID- 23135151
TI  - Effects of erythropoietin on osteoblast proliferation and function.
AB  - The purposes of this study were to investigate the effects of erythropoietin
      (EPO) on the proliferation and function of human osteoblast cells (hFOB 1.19)
      cultured in vitro and to explore the underlying molecular mechanisms to provide a
      theoretical foundation for clinical applications of EPO in oral implant and
      restoration therapies. Cultured hFOB 1.19 cells were treated with high and low
      doses of EPO. Changes in cell viability after 24 and 48 h of treatment were
      evaluated with the Mosmann tetrazolium assay. Changes in cell proliferation after
      48 h of EPO treatment were measured by bromodeoxyuridine (BrdU) labeling, and
      changes in alkaline phosphatase (ALP) activity were determined by a specific
      assay. The effects of EPO on osteocalcin secretion were determined with the
      enzyme-linked immunosorbent assay, and changes in the protein expression of
      osteoprotegerin (OPG), osteopontin (OPN) and receptor activator of NF-kappaB
      ligand (RANKL) were assayed by western blot. The effects of EPO treatment on the
      levels of the EPO receptor (EPOR), phosphorylated Jak2 (P-Jak2) and
      phosphorylated Stat3 (P-Stat3) in hFOB 1.19 cells were evaluated in conjunction
      with a Jak2/Stat3 inhibitor. After 24 h of EPO treatment, hFOB 1.19 cells showed
      increased cell viability compared with the blank control group (p < 0.05). After
      48 h, cell viability and growth were further improved relative to controls, with
      a significant increase observed for viability (p < 0.05). A significant increase
      in the proportion of BrdU-labeled proliferating cells was observed in the high
      dose EPO group (p < 0.05), and EPO-treated cells also showed enhanced ALP
      activity (p < 0.05). There were no statistically significant differences in
      osteocalcin secretion between groups after 48 h of EPO treatment (p > 0.05);
      however, increased secretion was observed in EPO-treated cells after 96 h of
      treatment (p < 0.05). EPO treatment significantly promoted OPG and OPN expression
      (p < 0.05) while significantly inhibiting RANKL expression (p < 0.01). EPO
      treatment also significantly upregulated the levels of EPOR, P-Jak2 and P-Stat3
      in hFOB 1.19 cells (p < 0.01); these effects were abrogated by co-treatment with
      a Jak2/Stat3 inhibitor (AG490) (p < 0.01). EPO significantly stimulated
      osteoblast proliferation and differentiation. The underlying molecular mechanism
      is associated with the ability of EPO to promote ALP activity, osteocalcin
      secretion and OPG and OPN expression and to inhibit RANKL expression in
      osteoblasts. This mechanism appears to be mediated by the Jak2/Stat3 pathway.

PMID- 23135152
TI  - Humic substances increase survival of freshwater shrimp Caridina sp. D to acid
      mine drainage.
AB  - Humic substances (HS) are known to decrease the toxicity of heavy metals to
      aquatic organisms, and it has been suggested that they can provide buffering
      protection in low pH conditions. Despite this, little is known about the ability
      for HS to increase survival to acid mine drainage (AMD). In this study, the
      ability of HS to increase survival of the freshwater shrimp (Caridina sp. D sensu
      Page et al. in Biol Lett 1:139-142, 2005) to acid mine drainage was investigated
      using test waters collected from the Mount Morgan open pit in Central Queensland
      with the addition of Aldrich humic acid (AHA). The AMD water from the Mount
      Morgan open pit is highly acidic (pH 2.67) as well as contaminated with heavy
      metals (1780 mg/L aluminum, 101 mg/L copper [Cu], 173 mg/L manganese, 51.8 mg/L
      zinc [Zn], and 51.8 mg/L iron). Freshwater shrimp were exposed to dilutions in
      the range of 0.5 % to 5 % AMD water with and without the addition of 10 or 20
      mg/L AHA. In the absence of HS, all shrimp died in the 2.5 % AMD treatment. In
      contrast, addition of HS increased survival in the 2.5 % AMD treatment by <=66 %
      as well as significantly decreased the concentration of dissolved Cu, cobalt,
      cadmium, and Zn. The decreased toxicity of AMD in the presence of HS is likely to
      be due to complexation and precipitation of heavy metals with the HS; it is also
      possible that HS caused changes to the physiological condition of the shrimp,
      thus increasing their survival. These results are valuable in contributing to an
      improved understanding of potential role of HS in ameliorating the toxicity of
      AMD environments.

PMID- 23135153
TI  - Nitrogenous and phosphorus excretions in juvenile silver catfish (Rhamdia quelen)
      exposed to different water hardness, humic acid, and pH levels.
AB  - This study examined ammonia, urea, creatinine, protein, nitrite, nitrate, and
      phosphorus (P) excretion at different water hardness, humic acid, or pH levels in
      silver catfish (Rhamdia quelen) juveniles. The fish were exposed to different
      levels of water hardness (4, 24, 50, or 100 mg L(-1) CaCO3), humic acid (0, 2.5,
      or 5.0 mg L(-1)), or pH (5.0, 6.0, 7.0, 8.0, or 9.0) for 10 days. The overall
      measured nitrogen excretions were 88.1% (244-423 MUmol kg(-1 )h(-1)) for ammonia,
      10.9% (30-52 MUmol kg(-1 )h(-1)) for creatinine, 0.02% (0.05-0.08 MUmol kg(-1 )h(
      1)) for protein, 0.001 % (0.002-0.004 MUmol kg(-1 )h(-1)) for urea, 0.5% (0.64
      3.6 MUmol kg(-1 )h(-1)) for nitrite, and 0.5% (0.0-6.9 MUmol kg(-1 )h(-1)) for
      nitrate, and these proportions were not affected by water hardness or humic acid
      levels. The overall P excretion in R. quelen was 0.14-2.97 MUmol kg(-1) h(-1).
      Ammonia excretion in R. quelen usually was significantly higher in the first 12 h
      after feeding, and no clear effect of water hardness, humic acid levels, and pH
      on this daily pattern of ammonia excretion could be observed. Water hardness only
      affected the ammonia and P excretion of R. quelen juveniles in the initial and
      fifth days after transfer, respectively. The exposure of this species to humic
      acid increased ammonia excretion after 10 days of exposure but did not affect P
      excretion. An increase in pH decreased ammonia and increased creatinine excretion
      but did not change P excretion in R. quelen. Therefore, when there is any change
      on humic acid levels or pH in the culture of this species, nitrogenous compounds
      must be monitored because their excretion rates are variable. On the other hand,
      P excretion rates determined in the present study are applicable to a wide range
      of fish culture conditions.

PMID- 23135154
TI  - Dietary Aloe vera components' effects on cholesterol lowering and estrogenic
      responses in juvenile goldfish, Carassius auratus.
AB  - Aloes are now considered a very interesting source of bioactive compounds among
      which phytosterols should play a major role. The present study is an attempt to
      investigate the hypocholesterolemic activity of Aloe vera associated with its
      impact on the reproductive status of juvenile goldfish. Therefore, the short- and
      long-term effects of feeding supplementary diet containing aloe components (20 mg
      aloe/g diet; 2%) on plasma lipids, plasma vitellogenin, and hepatic estrogen
      receptor alpha/beta1 mRNA levels in goldfish were examined. Results of GC-MS for
      phytosterols show high abundance of beta-sitosterol in freeze-dried powder of
      Aloe vera whole leaves. Moreover, a 2% aloe powder dietary supplement was not
      found estrogenic in juvenile goldfish after either 7- or 30-day treatment, but
      was consistent in plasma hypocholesterolemic effects following long-term
      exposure. The present data further support that plasma cholesterol modulation
      induced by phytosterols may not be related to estrogen-like activity.

PMID- 23135155
TI  - [Effort-reward imbalance at work and depression: current research evidence].
AB  - In view of highly prevalent stressful conditions in modern working life, in
      particular increasing work pressure and job insecurity, it is of interest to know
      whether specific constellations of an adverse psychosocial work environment
      increase the risk of depressive disorder among employed people. This contribution
      gives a short overview of current research evidence based on an internationally
      established work stress model of effort-reward imbalance. Taken together, results
      from seven prospective epidemiological investigations demonstrate a two-fold
      elevated relative risk of incident depressive disorder over a mean observation
      period of 2.7 years among exposed versus non-exposed employees. Additional
      findings from experimental and quasi-experimental studies point to robust
      associations of effort-reward imbalance at work with proinflammatory cytokines
      and markers of reduced immune competence. These latter markers may indicate
      potential psychobiological pathways. In conclusion, incorporating this new
      knowledge into medical treatment and preventive efforts seems well justified.

PMID- 23135156
TI  - Results of metal-on-metal hip resurfacing in patients 40 years old and younger.
AB  - The prevalence of total hip arthroplasty in young patients is small but
      increasing. We analyzed the results of metal-on-metal hip resurfacing (MMHR) in
      patients aged 40 years or less. In total 74 operations were performed on 64
      patients. Mean age at operation was 33.2 years. HHS averaged 92.3 points at
      latest follow-up, mean UCLA activity was 8.2. Patients with comorbidity evinced
      lower scores in HHS, in UCLA activity and in quality of life than patients
      without comorbidities. Eight revisions (10.8 %) were performed, of which seven
      due to adverse reaction to metal debris. Seven-year survival was 90.5 %. The
      functional outcome of hip resurfacing in this cohort was excellent, but overall
      survival was unsatisfactory. Further analysis is required to verify the role of
      hip resurfacing among young and active patients.

PMID- 23135158
TI  - Construction of boundary-surface-based Chinese female astronaut computational
      phantom and proton dose estimation.
AB  - With the rapid development of China's space industry, the importance of radiation
      protection is increasingly prominent. To provide relevant dose data, we first
      developed the Visible Chinese Human adult Female (VCH-F) phantom, and performed
      further modifications to generate the VCH-F Astronaut (VCH-FA) phantom,
      incorporating statistical body characteristics data from the first batch of
      Chinese female astronauts as well as reference organ mass data from the
      International Commission on Radiological Protection (ICRP; both within 1%
      relative error). Based on cryosection images, the original phantom was
      constructed via Non-Uniform Rational B-Spline (NURBS) boundary surfaces to
      strengthen the deformability for fitting the body parameters of Chinese female
      astronauts. The VCH-FA phantom was voxelized at a resolution of 2 * 2 * 4
      mm(3)for radioactive particle transport simulations from isotropic protons with
      energies of 5000-10 000 MeV in Monte Carlo N-Particle eXtended (MCNPX) code. To
      investigate discrepancies caused by anatomical variations and other factors, the
      obtained doses were compared with corresponding values from other phantoms and
      sex-averaged doses. Dose differences were observed among phantom calculation
      results, especially for effective dose with low-energy protons. Local skin
      thickness shifts the breast dose curve toward high energy, but has little impact
      on inner organs. Under a shielding layer, organ dose reduction is greater for
      skin than for other organs. The calculated skin dose per day closely approximates
      measurement data obtained in low-Earth orbit (LEO).

PMID- 23135157
TI  - Effects of expression level of DNA repair-related genes involved in the NHEJ
      pathway on radiation-induced cognitive impairment.
AB  - Cranial radiation therapy can induce cognitive decline. Impairments of
      hippocampal neurogenesis are thought to be a paramountly important mechanism
      underlying radiation-induced cognitive dysfunction. In the mature nervous system,
      DNA double-strand breaks (DSBs) are mainly repaired by non-homologous end-joining
      (NHEJ) pathways. It has been demonstrated that NHEJ deficiencies are associated
      with impaired neurogenesis. In our study, rats were randomly divided into five
      groups to be irradiated by single doses of 0 (control), 0 (anesthesia control),
      2, 10, and 20 Gy, respectively. The cognitive function of the irradiated rats was
      measured by open field, Morris water maze and passive avoidance tests. Real-time
      PCR was also used to detect the expression level of DNA DSB repair-related genes
      involved in the NHEJ pathway, such as XRCC4, XRCC5and XRCC6, in the hippocampus.
      The influence of different radiation doses on cognitive function in rats was
      investigated. From the results of the behavior tests, we found that rats
      receiving 20 Gy irradiation revealed poorer learning and memory, while no
      significant loss of learning and memory existed in rats receiving irradiation
      from 0-10 Gy. The real-time PCR and Western blot results showed no significant
      difference in the expression level of DNA repair-related genes between the 10 and
      20 Gy groups, which may help to explain the behavioral results, i.e. DNA damage
      caused by 0-10 Gy exposure was appropriately repaired, however, damage induced by
      20 Gy exceeded the body's maximum DSB repair ability. Ionizing radiation-induced
      cognitive impairments depend on the radiation dose, and more directly on the
      body's own ability to repair DNA DSBs via the NHEJ pathway.

PMID- 23135159
TI  - Protection of guinea pigs by vaccination with a recombinant swinepox virus co
      expressing HA1 genes of swine H1N1 and H3N2 influenza viruses.
AB  - Swine influenza (SI) is an acute respiratory infectious disease of swine caused
      by swine influenza virus (SIV). SIV is not only an important respiratory pathogen
      in pigs but also a potent threat to human health. Here, we report the
      construction of a recombinant swinepox virus (rSPV/H3-2A-H1) co-expressing
      hemagglutinin (HA1) of SIV subtypes H1N1 and H3N2. Immune responses and
      protection efficacy of the rSPV/H3-2A-H1 were evaluated in guinea pigs.
      Inoculation of rSPV/H3-2A-H1 yielded neutralizing antibodies against SIV H1N1 and
      H3N2. The IFN-gamma and IL-4 concentrations in the supernatant of lymphocytes
      stimulated with purified SIV HA1 antigen were significantly higher (P < 0.01)
      than those of the control groups. Complete protection of guinea pigs against SIV
      H1N1 or H3N2 challenge was observed. No SIV shedding was detected from guinea
      pigs vaccinated with rSPV/H3-2A-H1 after challenge. Most importantly, the guinea
      pigs immunized with rSPV/H3-2A-H1 did not show gross and micrographic lung
      lesions. However, the control guinea pigs experienced distinct gross and
      micrographic lung lesions at 7 days post-challenge. Our data suggest that the
      recombinant swinepox virus encoding HA1 of SIV H1N1 and H3N2 might serve as a
      promising candidate vaccine for protection against SIV H1N1 and H3N2 infections.

PMID- 23135160
TI  - Modulation of feeding by chronic rAAV expression of a relaxin-3 peptide agonist
      in rat hypothalamus.
AB  - Relaxin-3 is a neuropeptide that is abundantly expressed by discrete brainstem
      neuron populations that broadly innervate forebrain areas rich in the relaxin-3 G
      protein-coupled-receptor, RXFP3. Acute and subchronic central administration of
      synthetic relaxin-3 or an RXFP3-selective agonist peptide, R3/I5, increase
      feeding and body weight in rats. Intrahypothalamic injection of relaxin-3 also
      increases feeding. In this study, we developed a recombinant adeno-associated
      virus 1/2 (rAAV1/2) vector that drives expression and constitutive secretion of
      bioactive R3/I5 and assessed the effect of intrahypothalamic injections on daily
      food intake and body weight gain in adult male rats over 8 weeks. In vitro
      testing revealed that the vector rAAV1/2-fibronectin (FIB)-R3/I5 directs the
      constitutive secretion of bioactive R3/I5 peptide. Bilateral injection of rAAV1/2
      FIB-R3/I5 vector into the paraventricular nucleus produced an increase in daily
      food intake and body weight gain (P<0.01, ~23%, respectively), relative to
      control treatment. In a separate cohort of rats, quantitative polymerase chain
      reaction analysis of hypothalamic mRNA revealed strong expression of R3/I5
      transgene at 3 months post-rAAV1/2-FIB-R3/I5 infusion. Levels of mRNA transcripts
      for the relaxin-3 receptor RXFP3, the hypothalamic 'feeding' peptides
      neuropeptide Y, AgRP and POMC, and the reproductive hormone, GnRH, were all
      similar to control, whereas vasopressin and oxytocin (OT) mRNA levels were
      reduced by ~25% (P=0.051) and ~50% (P<0.005), respectively, in rAAV1/2-FIB-R3/I5
      treated rats (at 12 weeks, n=9/8 rats per group). These data demonstrate for the
      first time that R3/I5 is effective in modulating feeding in the rat by chronic
      hypothalamic RXFP3 activation and suggest a potential underlying mechanism
      involving altered OT signalling. Importantly, there was no desensitization of the
      feeding response over the treatment period and no apparent deleterious health
      effects, indicating that targeting the relaxin-3-RXFP3 system may be an effective
      long-term therapy for eating disorders.

PMID- 23135165
TI  - Patterns of symptom reporting during pregnancy comparing opioid maintained and
      control women.
AB  - OBJECTIVE: To characterize the range of symptoms experienced by pregnant
      methadone-maintained (MM) and buprenorphine-maintained (BM) women to determine
      whether these differ from those experienced by a control group of nonopioid
      exposed pregnant women. Opioid-maintained (OM) patients report high rates of
      symptoms related to direct opioid effects and withdrawal. Pregnancy is associated
      with a range of symptoms, some overlapping with opioid effects and withdrawal.
      METHODS: Prospective, nonrandomized, open-label comparison study undertaken in a
      large teaching maternity hospital in South Australia. Pregnant BM (n = 25), MM (n
      = 25) and nonopioid exposed controls (n = 25) were recruited and matched for age,
      parity, gravidity, alcohol consumption, and smoking status. Symptom report
      patterns, maternal withdrawal, and additional substance use were assessed.
      RESULTS: MM women reported 10 and BM women reported 2 symptoms throughout
      pregnancy at rates greater than controls. Methadone-maintained women reported
      significantly (P < 0.05) more symptoms than BM women compared to controls
      throughout pregnancy. Methadone-maintained women reported 8 and BM women reported
      3 symptoms in the third trimester at rates greater than controls. Methadone
      maintained women reported greater opioid withdrawal than controls; this did not
      occur in BM women. Additional substance use was comparable between BM and MM
      women but greater than controls. CONCLUSIONS: Patterns of symptom reports may
      have clinical implications for maternal and fetal health during pregnancy for OM
      women including optimization of opioid dosing regimens, education regarding
      maternal nutritional intake and preventing postnatal depression, thereby ensuring
      maternal health and fetal development during pregnancy and enhancing mother
      infant bonding and healthy child development postnatally.

PMID- 23135166
TI  - Optimally efficient swimming in hyper-redundant mechanisms: control, design, and
      energy recovery.
AB  - Hyper-redundant mechanisms (HRMs), also known as snake-like robots, are highly
      adaptable during locomotion on land. Researchers are currently working to extend
      their capabilities to aquatic environments through biomimetic undulatory
      propulsion. In addition to increasing the versatility of the system, truly
      biomimetic swimming could also provide excellent locomotion efficiency.
      Unfortunately, the complexity of the system precludes the development of a
      functional solution to achieve this. To explore this problem, a rapid
      optimization process is used to generate efficient HRM swimming gaits. The low
      computational cost of the approach allows for multiple optimizations over a broad
      range of system conditions. By observing how these conditions affect optimal
      kinematics, a number of new insights are developed regarding undulatory swimming
      in robotic systems. Two key conditions are varied within the study, swimming
      speed and energy recovery. It is found that the swimmer mimics the speed control
      behaviour of natural fish and that energy recovery drastically increases the
      system's efficiency. Remarkably, this efficiency increase is accompanied by a
      distinct change in swimming kinematics. With energy recovery, the swimmer
      converges to a clearly anguilliform gait, without, it tends towards the
      carangiform mode.

PMID- 23135167
TI  - Biobanking past, present and future:  responsibilities and benefits.
AB  - The review explores the field of biobanking as it has evolved from a simple
      collection of frozen specimens to the virtual biobank. Biorepository and
      biospecimen science has evolved in response to the changing landscape of external
      regulatory pressures, the advances made in the biological sciences, and the
      advent of the computer chip. Biospecimen banking is a growing enterprise crucial
      to health science research and other biological sciences. In this review we
      discuss the history of biobanking, highlight current and emerging issues, discuss
      demands and responses, and describe an example of a biobank, the University of
      California, San Francisco AIDS Specimen Bank that has functioned for 30 years.

PMID- 23135168
TI  - CD3+CD8+CD161high Tc17 cells are depleted in HIV-infection.
AB  - CD8 Tc17 cells with pro-inflammatory properties have only recently been
      acknowledged, and Tc17 cells in HIV-infection are not described. CD3CD8CD161 Tc17
      cells and the production of interleukin (IL)-17 were examined in untreated and
      treated HIV-infected patients, HIV-hepatitis C virus co-infected patients, and
      healthy controls. Depletion of CD3CD8CD161 Tc17 cells and diminished production
      of IL-17 in HIV-infected patients were found. The level of Tc17 cells was
      associated with the CD4 cell count in treated patients.

PMID- 23135169
TI  - Effect of hormonal contraceptive methods on HIV disease progression: a systematic
      review.
AB  - OBJECTIVE: Systematically assess from the literature whether women living with
      HIV who use hormonal contraception are at increased risk of HIV-disease
      progression compared with those who do not use hormonal contraception. METHODS:
      We searched PUBMED and EMBASE for articles published in peer-reviewed journals
      through December 15, 2011 for evidence relevant to all hormonal contraceptive
      methods and HIV-disease progression. RESULTS: Twelve reports of 11 studies met
      inclusion criteria. One randomized controlled trial (RCT) found increased risk
      for the composite outcome of a reduced CD4 cell count or death among hormonal
      contraceptive users when compared with copper intrauterine device (IUD) users.
      Ten cohort studies reported no increased risk for HIV disease progression (as
      measured by mortality, time to a CD4 cell count below 200, time to initiation of
      antiretroviral therapy, an increase in HIV-RNA viral load, or a decrease in CD4
      count) among women who used hormonal contraception compared with those who did
      not. CONCLUSION: The preponderance of evidence indicates that HIV-positive women
      can use hormonal contraceptive methods without concerns related to HIV-disease
      progression. Cohort studies consistently found no association between hormonal
      contraceptive use and HIV-disease progression compared with nonuse of hormonal
      contraceptives. One RCT found that hormonal contraceptive use was associated with
      increased risk of HIV-disease progression when compared with IUD use, but this
      study had important methodological shortcomings. Prevention of unintended
      pregnancy among women living with HIV remains a public health priority to
      safeguard women's and infants' health and to prevent vertical transmission of
      HIV.

PMID- 23135170
TI  - Performance of a fourth-generation HIV screening assay and an alternative HIV
      diagnostic testing algorithm.
AB  - OBJECTIVE: We evaluated the performance of the GS fourth-generation
      antigen/antibody assay and compared Centers for Disease Control and Prevention's
      (CDC's) proposed alternative algorithm [repeatedly reactive fourth-generation
      immunoassay followed by an HIV-1/HIV-2 differentiation immunoassay and, if
      needed, nucleic acid test (NAT)] with the current algorithm (repeatedly reactive
      third-generation immunoassay followed by HIV-1 western blot). DESIGN: A
      convenience sample of the following four specimen sets was acquired: 10 014 from
      insurance applicants, 493 known western blot-positive, 20 known western blot
      indeterminate specimens, and 230 specimens from 26 HIV-1 seroconverters. METHODS:
      Specimens were tested with the GS third-generation and fourth-generation
      immunoassays, the Multispot HIV-1/HIV-2 differentiation immunoassay, NAT, and
      western blot. We applied the two algorithms using these results. RESULTS: Among
      insurance specimens, 13 (0.13%) specimens were immunoassay repeatedly reactive:
      two were HIV-positive (repeatedly reactive by third-generation and fourth
      generation immunoassays, and western blot and Multispot positive); two third
      generation repeatedly reactive and nine fourth-generation repeatedly reactive
      specimens were false-positive. Third-generation and fourth-generation
      specificities were 99.98% [95% confidence interval (CI) 99.93-100%] and 99.91%
      (95% CI 99.84-99.96%), respectively.All HIV-1 western blot-positive specimens
      were repeatedly reactive by third-generation and fourth-generation immunoassays.
      By Multispot, 491 (99.6%) were HIV-1-positive and two (0.4%) were HIV-2
      positive.Only eight (40%) western blot-indeterminate specimens were fourth
      generation repeatedly reactive: six were Multispot and NAT-negative and two were
      Multispot HIV-1-positive but NAT-negative.The alternative algorithm correctly
      classified as positive 102 seroconverter specimens with the third-generation
      immunoassay and 130 with the fourth-generation immunoassay compared with 56 using
      the western blot with either immunoassay. CONCLUSION: The alternative testing
      algorithm improved early infection sensitivity and identified HIV-2 infections.
      Two potential false-positive algorithm results occurred with western blot
      indeterminate specimens.

PMID- 23135171
TI  - Decoupling activation and exhaustion of B cells in spontaneous controllers of HIV
      infection.
AB  - OBJECTIVE: To define the impact of chronic viremia and associated immune
      activation on B-cell exhaustion in HIV infection. DESIGN: Progressive HIV
      infection is marked by B-cell anergy and exhaustion coupled with dramatic
      hypergammaglobulinemia. Although both upregulation of CD95 and loss of CD21 have
      been used as markers of infection-associated B-cell dysfunction, little is known
      regarding the specific profiles of dysfunctional B cells and whether persistent
      viral replication and its associated immune activation play a central role in
      driving B-cell dysfunction. METHODS: Multiparameter flow cytometry was used to
      define the profile of dysfunctional B cells. The changes in the expression of
      CD21 and CD95 were tracked on B-cell subpopulations in patients with differential
      control of viral replication. RESULTS: : Although the emergence of exhausted,
      CD21 tissue-like memory B cells followed similar patterns in both progressors and
      controllers, the frequency of CD21 activated memory B cells was lower in
      spontaneous controllers. CONCLUSION: Our results suggest that the loss of CD21
      and the upregulation of CD95 occur as separate events during the development of B
      cell dysfunction. The loss of CD21 is a marker of B-cell exhaustion induced in
      the absence of appreciable viral replication, whereas the upregulation of CD95 is
      tightly linked to persistent viral replication and its associated immune
      activation. Thus, these dysfunctional profiles potentially represent two
      functionally distinct states within the B-cell compartment.

PMID- 23135173
TI  - Analysis of IL28B alleles with virologic response patterns and plasma cytokine
      levels in HIV/HCV-coinfected patients.
AB  - OBJECTIVES: To estimate the impact of interleukin 28B (IL28B) polymorphisms
      (rs12980275, rs8099917, rs7248668, and rs11881222) and their haplotypes on
      hepatitis C virus (HCV) treatment (peg-interferon-alpha and ribavirin) success in
      324 HIV/HCV-coinfected patients. We also explore the behavior of plasma cytokine
      levels. DESIGN: Retrospective follow-up study. METHODS: Virologic response to HCV
      treatment was measured by plasma HCV viral load at different endpoints: rapid
      virologic response (RVR), early virologic response (EVR), end-of-treatment
      virologic response (ETVR) and sustained virologic response (SVR). IL28B
      polymorphisms were genotyped using GoldenGate assay. Finally, 13 cytokines were
      measured at baseline in 57 plasma samples using a multiplex immunoassay kit.
      RESULTS: IL28B polymorphisms were strongly associated to virologic responses
      (RVR, EVR, ETVR, and SVR), although only for HCV genotypes 1 and 4 (P < 0.05).
      Strong linkage disequilibrium was detected for rs12980275/rs11881222 (r = 0.94)
      and rs8099917/rs7248668 (r = 0.99). IL28B haplotypes showed association but no
      improvement on treatment outcome prediction. Thus, the genotyping of only one
      single-nucleotide polymorphism was enough for predicting treatment response in
      GT1/4 patients with favorable rs12980275 (AA) genotype, while for subjects
      harboring unfavorable genotypes, the inclusion of rs8099917 was useful (SVR
      increased from 31 to 45%). Moreover, patients with rs12980275 (AA) that achieved
      SVR showed reduced plasma levels of Th1 (IFN-gamma), Th2 (IL-6 and IL-9), and
      proinflammatory (TNF-alpha) cytokines. CONCLUSION: The presence of IL28B
      polymorphisms was significantly associated with HCV clearance during and after
      HCV therapy. The evaluated cytokine profile was much more favorable in patients
      with rs12980275 (AA) who achieved SVR.

PMID- 23135174
TI  - [The study of osteogenic differentiation in canine bone marrow stromal cell
      induced by point mutant type of HIF-1alpha].
AB  - PURPOSE: To evaluate osteogenesis in canine bone marrow mesenchymal stem
      cells(BMSCs) transduced by point mutant HIF-1alpha. METHODS: Lenti-WT (wild type
      HIF-1alpha), Lenti-MT (mutant type HIF-1alpha), and Lenti-LacZ (the control
      group) were constructed with LR recombination system. And then Lenti-LacZ, Lenti
      WT and Lenti-MT were used to transduce canine BMSCs. After transduction, total
      RNA and protein were extracted at 0 , 1 , 4 , 7, 14 d and 21 d, respectively. The
      mRNA and protein expression of osteogenic factors were detected by RT-PCR and
      Western blot in vitro under normoxic conditions.To further prove osteogenic
      differentiation of HIF-1alpha mediated BMSCs, the BMSCs were inoculated into 6
      well plate (2*10(5)/well) and then the expression of calcium nodules was measured
      using Alizarin red staining(ARS) at 14 d and 21 d, respectively. RESULTS: At
      MOI=9, the transduced efficiency of BMSCs was up to 90%. After target gene being
      transduced to BMSCs, the mRNA and protein expression of osteogenic factors were
      significantly up-regulated at 4d, reached peak at 14-21 d and maintained a state
      of high expression (P<0.05). ARS results showed that the target gene can induce
      BMSCs to the osteogenic differentiation in normoxic conditions. CONCLUSIONS:
      Under normoxic conditions in vitro, mutant HIF-1alpha can stabilize the
      expression and maintain a high level of activity. Lenti-MT can significantly
      improve the osteogenic activity of canine BMSCs.

PMID- 23135175
TI  - [Influence of La2O3 and Li2O on glass powder for infiltrating ZTA all-ceramic
      dental material formed by gel-casting].
AB  - PURPOSE: The influence of La2O3 and Li2O on glass powder was studied in this
      paper, which is to infiltrate ZTA all-ceramic dental material formed by gel
      casting. The performance of different component was analyzed to optimize glass
      formula. METHODS: Six groups of glass powder were designed and prepared by
      conventional melt-quenching method. ZTA ceramic blocks were covered with glass
      paste, which were formed by gel-casting and sintered in 1200 degrees centigrade,
      then infiltrated in 1150 degrees centigrade for twice to make glass/ZTA ceramic
      composites. By detecting differential thermal analysis and melting range of
      infiltration glass power, as well as flexural strength, linear shrinkage, SEM and
      EDS of glass/ZTA ceramic composites, the optimized glass group was determined
      out. Statistical analysis was performed using SPSS 13.0 software package by means
      of paired t test or one way ANOVA. RESULTS: The bending strength of group Li1 was
      (291.2+/-27.9) MPa, significantly higher than group Li2 and group La2(P<0.05),
      and linear shrinkage of group Li1 was only(1.85+/-0.27)%. SEM and EDS showed
      glass of group Li1 can lubricate ZTA ceramics well, their structure was compact
      and had a few small pores. Intergranular fracture existed on cross surface as
      well as transgranular fracture. CONCLUSIONS: The results showed that Li1(30%La2O3
      15%Al2O3-15%SiO2-15%B2O3-5%Li2O) glass infiltrated ZTA ceramic composite had the
      best capability. Glass/ZTA composite material can be prepared by gel-casting and
      infiltrating way, and this process is simple and economically suitable for
      general dental laboratory.

PMID- 23135176
TI  - [Effect of pamidronate on cementoclast and osteoclast differentiation factor
      expression during orthodontic tooth movement in rats].
AB  - PURPOSE: To investigate the influence of pamidronate on cementoclast and
      osteoclast differentiation factor(ODF) expression during orthodontic tooth
      movement in rats. METHODS: 24 female, 6-week-old SPF Wistar rats were selected
      and the animal models for orthodontic tooth movement were established. Each rat's
      maxillary was divided into experimental side and control side. Pamidronate(50
      MUL) was injected into the sub-periosteum area adjacent to the left upper first
      molar(experimental side) every 3 days during the experiment, while 0.9%NS(50 MUL)
      was injected into the corresponding area of the control side. The rats were
      executed in batch on the 3rd, 7th and 14th day respectively during the
      orthodontic treatment for detecting the amount of cementoclast and the expression
      of ODF in the periodontal tissues. All statistical analysis was performed using
      PASW Statistics 18 software package. RESULTS: The amount of cementoclasts was
      significantly less in the experimental side than that in the control side on the
      7th and 14th days(P<0.05). The expression of ODF was significantly less in the
      experimental side than that in the control side on the 7th and 14th days(P<0.05).
      CONCLUSIONS: Local injection of pamidronate can reduce the number of cementoclast
      and the expression of ODF.

PMID- 23135172
TI  - Outcomes after reinitiating antiretroviral therapy in children randomized to
      planned treatment interruptions.
AB  - BACKGROUND: Excess risks for death/opportunistic disease in adults randomized to
      CD4-driven planned treatment interruption (PTI) in the Strategies for Management
      of Antiretroviral Therapy (SMART) trial remained after antiretroviral therapy
      (ART) re-initiation. Risks for children following PTI were evaluated in long-term
      follow-up of children in the PENTA 11 trial. METHODS: Children with HIV RNA below
      50 copies/ml and CD4 at least 30% (2-6 years) or at least 500 cells/MUl (7-15
      years) were randomized to continuous ART (cART) or PTI in PENTA 11 (ISRCTN
      36694210). After the end of the trial, all were recommended to resume ART. Data
      were collected annually and analysed up to the second year of visit. RESULTS: One
      hundred and one (51 cART, 50 PTI; median baseline age 9.2 years) children had
      median overall follow-up 4.6 (range 3.7-5.0) years. During 2-year post-trial
      period, there were no deaths or new Centers for Disease Control and Prevention
      (CDC) stage B/C events. Rate of clinical grade of at least two events was similar
      between PTI and cART [relative risk (RR) 1.03; 95% confidence interval (CI) 0.43,
      2.50; P = 0.94]. At 2 years, difference in absolute CD4% between PTI and cART was
      -1.6% (-4.5%; 1.3%; P = 0.27), and proportions with HIV RNA below 50 copies/ml
      were 82 versus 86% (P = 0.57), respectively; no differences in growth or fasting
      lipids were observed. Key predictors of greater CD4% recovery after re-initiating
      ART were higher CD4% at baseline (P < 0.001) and longer time since ART re
      initiation (P < 0.001). During overall follow-up, 4 (8%) PTI versus 5 (10%) CT
      children switched ART for failure (P = 0.75) and 9 (18%) versus 1 (2%) (P =
      0.008) substituted ART for simplification. CONCLUSIONS: No adverse clinical,
      immunological or virological consequences of PTI were observed 2 years after the
      end of PENTA 11 trial. Although ART interruption is not generally recommended, it
      may be an acceptable option for children, particularly when there is high risk of
      unplanned treatment interruptions.

PMID- 23135177
TI  - [Expression of HIF-1alpha and VEGF in human dental pulp cells under mechanical
      stretch].
AB  - PURPOSE: To examine the expression of HIF-1alpha and VEGF after application of
      mechanical stretch on human dental pulp cells (HDPCs), and to investigate the
      role of them in maintaining homeostasis of dental pulp during orthodontic
      movement. METHODS: HDPCs were subjected to 15% elongation by 1.0 Hz stretching
      frequency for 6, 12, 24, 48 and 72 h. The expression of HIF-1alpha and VEGF mRNA
      was measured by real-time polymerase chain reaction (PCR). SPSS12.0 software
      package was applied for statistical analysis. RESULTS: At the initial time point,
      HIF-1alpha mRNA had a weak expression. The mRNA level of HIF-1alpha increased
      gradually and then decreased towards its pre-pressure levels. The mRNA level of
      VEGF was upregulated in a time-dependent manner. CONCLUSIONS: The mRNA expression
      of HIF-1alpha and VEGF was enhanced by mechanical stress in HDPCs, which
      indicates that HIF-1alpha and VEGF may play an important role in retaining
      homeostasis of dental pulp during orthodontic movement.

PMID- 23135178
TI  - [Ultramicrostructural study of pathological changes of capillary vessels in pulp
      tissues of diabetes mellitus patients].
AB  - PURPOSE: To investigate the relationship between diabetes mellitus and pulposis
      and the pathogenesis of diabetes mellitus pulposis, via comparing the pulp tissue
      conditions and ultramicrostructures of capillary vessels in pulp tissues of
      diabetes mellitus patients and normal control. METHODS: Pulp tissues were
      obtained from clinically extracted human third molars with impaction (control
      group, 30 cases) and intact third molars with impaction (non-insulin dependent
      diabetes patients) whilst without pulposis symptom (diabetic group, 30 cases).
      The pathological changes of two groups' pulp tissues were evaluated under light
      microscope and electron microscopy. The thickness of pulp capillary basement
      membrane and their anionic sites were quantitatively analyzed by electron
      microscopy and special staining. Statistical analysis was performed using SAS6.12
      software package. RESULTS: The tricked blood capillary wall was observed in
      diabetic pulp under light microscope. The thickened blood capillary wall and
      constrictive lumen were observed in diabetic pulp under electron microscope,
      accompanied with vascular endothelial cell swelling and structural destruction
      and thickened basement membrane (P<0.01). The decrease of anionic sites of
      capillary basement membrane was observed in diabetic pulp under specially stained
      electron microscope (P<0.01). CONCLUSIONS: Inflammatory reaction existed in the
      pulp of intact teeth of DM patients without symptoms. The changes observed in
      diabetic vessels may occur in the dental pulp. Diabetes mellitus is closely
      related to pulposis.

PMID- 23135179
TI  - [The activity of osteoclast in peri-implant tissues in Beagle dogs].
AB  - PURPOSE: To observe the quantity and activity of osteoclast in peri-implant
      tissues dynamically. METHODS: An animal model of dental implants was established
      in 6 male Beagle dogs of 1-2 years old. Bone remodeling was tested at 3-, 7-,15
      ,30-,60- and 90-day after placement of implants. The mandibular bones were taken
      out and the morphological changes were observed under X-ray examination.Bone
      tissue samples underwent HE staining. The data were analyzed with SPSS13.0
      software package. RESULTS: The most prominent period of osteoclasts occurred at 7
      day after placement of implants. After 7 days of implantation, the activity of
      osteoclast gradually decreased. CONCLUSIONS: The active stage for bone
      remodelling in peri-implant tissues during unloading period is about 7 days after
      implantation.

PMID- 23135180
TI  - [Attachment and spreading of fibroblasts on titanium coatings by different micro
      arc oxidation time].
AB  - PURPOSE: To investigate the attachment and spreading of fibroblasts on titanium
      coatings by different micro-arc oxidation(MAO) time. METHODS: Micro-arc oxidation
      film was formed on the titanium surface by using micro-arc oxidation. The film
      morphology and the cell shape on the samples were observed by scanning electron
      microscopy (SEM) and the surface roughness of film with different time was
      analyzed by surface coarseness profiling instrument. SPSS11.5 software package
      was used to analyze the data. RESULTS: The experiment result showed, the coatings
      were rough and porous, the longer oxidation time, the larger diameter of porous
      but the less porous numbers. As the treatment time increased, the surface
      roughness of micro-arc oxidation specimens increased (P<0.05). Compared with
      titanium, fibroblasts on titanium MAO coatings had more abundant spreading and
      adhesion. At 24 h, 48 h and 72 h, the cell number on coatings adhesion increased,
      but with different oxidation time, the cell shape, number and adhesion weren't
      obviously changed. CONCLUSIONS: The results indicate that microarc oxidation
      increases the surface roughness, have a good influence on cell adhesion and
      spreading.

PMID- 23135181
TI  - [Differential expression genes of bone tissues surrounding implants in diabetic
      rats by gene chip].
AB  - PURPOSE: To compare mRNA expression profiles of bone tissues surrounding implants
      between normal rats and rats with diabetes using microarray technology. METHODS:
      Six Wistar rats were randomly selected and divided into normal model group and
      diabetic group. Diabetic model condition was established by injecting
      Streptozotocin into peritoneal space. Titanium implants were implanted into the
      epiphyseal end of the rats' tibia. Bone tissues surrounding implant were
      harvested and sampled after 3 months to perform comprehensive RNA gene expression
      profiling, including 17983 for genome-wide association study.GO analysis was used
      to compare different gene expression and real-time PCR was used to confirm the
      results on core samples. RESULTS: The results indicated that there were 1084
      differential gene expression. In the diabetic model, there were 352 enhanced
      expression genes, 732 suppressed expression genes. GO analysis involved 1154
      different functional type. CONCLUSIONS: Osteoblast related gene expressions in
      bone tissue samples of diabetic rats were decreased, and lipid metabolism pathway
      related gene expression was increased.

PMID- 23135182
TI  - [Effect of insulin on prohibitin in the osteogenic differentiation of rat's
      mandibular bone marrow stromal cells in high glucose].
AB  - PURPOSE: To explore the effect of insulin on the expression of prohibitin in
      osteogenic differentiation of rat's mandibular bone marrow stromal cells(BMSC) in
      high glucose. METHODS: Bone marrow stromal cells were obtained from the mandible
      of Wistar rats and stimulated in three glucose concentrations mineral medium(5.5,
      25, 45 mM) with or without insulin(10-5 M) for 1, 3, 7,14 and 21 days. The
      expression of prohibitin was quantified via enzyme-linked immunosorbent assays
      (ELISA). The mineralization nodules assessment was performed at day 21 by
      alizarine red staining. The statistics analysis was performed using SPSS 15.0
      software package. RESULTS: High glucose of 45 mM inhibited mineralization of
      rBMSC and insulin could improve the mineralization in high glucose. The
      expression of prohibitin of 45 mM group decreased significantly compared with 5.5
      mM group and 25 mM group. The expression of prohibitin of each group achieved
      maximum at day 3. Insulin (10-5 M) increased the expression of prohibitin of 25
      mM group and 45 mM group in osteogenic differentiation of rBMSC. CONCLUSIONS:
      High glucose inhibited the expression of prohibitin in osteogenic differentiation
      of rBMSC, and insulin can improve the effect. Prohibitin may play an important
      part in early stage in osteogenic differentiation of rBMSC.

PMID- 23135183
TI  - [Cross-sectional morphology and wall thickness of the root canal system in
      mandibular first premolars with C-shaped root evaluated by cone-beam CT].
AB  - PURPOSE: To analyze the cross-sectional morphology of the root canal system in
      mandibular first premolars with C-shaped root and measure the minimum canal wall
      thickness. METHODS: 44 mandibular first premolars with C-shaped root were
      selected. The specimens were scanned by cone-beam computed tomography and 3D
      images of each specimen were reconstructed. The distribution of cross-sectional
      morphology of root canals in different portion of the roots was analyzed and
      compared. And measurement of the minimum canal wall thickness in the radicular
      groove aspect and the opposite aspect in different portion of the roots was
      taken. SPSS13.0 software package was used to perform the statistical analysis.
      RESULTS: The distribution of cross-sectional morphology of root canals was
      complex in the middle 1/3 and apical 1/3, mainly in types C2, C3 and C4, which
      was different from that of cervical 1/3(P<0.05). The minimum canal wall thickness
      in the radicular groove aspect was thinner than that in the opposite aspect of
      both middle 1/3 and apical 1/3(P<0.05). And the value of the minimum canal wall
      thickness in both middle 1/3 and apical 1/3 was less than 1mm. CONCLUSIONS:
      Morphology of root canals in mandibular first premolars with C-shaped root was
      complex in apical 2/3 of the roots and the canal wall thickness was thinner in
      the radicular groove aspect. These factors should be considered in clinical
      treatment.

PMID- 23135184
TI  - [Exploration for micro-osteotomy assisted orthodontic treatment of skeletal Class
      III malocclusions with alveolar hypoplasia in the lower anterior region].
AB  - PURPOSE: To investigate the changes of periodontal conditions after micro
      osteotomy assisted lower incisor decompensation for skeletal Class III
      malocclusions with alveolar hypoplasia in the lower anterior region. METHODS: The
      sample consisted of 22 cases diagnosed as skeletal Class III malocclusions with
      alveolar hypoplasia in the lower anterior region, selected from consecutive
      patients of Department of Oral & Cranio-maxillofacial Science of Shanghai Ninth
      People's Hospital during 2009-2012. The samples were divided into 2 groups; G1
      comprised 10 patients who accepted micro-osteotomy assisted lower incisor
      decompensation; G2 comprised 12 patients who chose traditional pre-surgical
      decomposition. The changes of periodontal conditions of both groups were
      evaluated with the help of cone-beam CT(CBCT). Data was processed using SAS8.02
      software package. RESULTS: For subjects in G1, during the micro-osteotomy
      assisted pre-surgical orthodontics, no significant difference was found in the
      amount of root resorption of lower incisors.But labial and lingual vertical
      alveolar bone loss were 2.60 mm and 2.22 mm; alveolar bone thickness increased by
      3.05 mm on the labial side and decreased by 0.88 mm on the lingual side (P<0.05).
      Better periodontal conditions were reserved compared with those of G2.
      CONCLUSIONS: Micro-osteotomy assisted pre-surgical orthodontics was much safer
      than traditional orthodontics for skeletal Class III malocclusions with alveolar
      hypoplasia in the lower anterior region.

PMID- 23135185
TI  - [Papilla alteration in different gingival biotypes at single implant-supported
      restoration in anterior maxilla].
AB  - PURPOSE: To observe the alteration of the interproximal papilla height after
      single implant restoration in the anterior maxilla and to assess the influence of
      gingival biotypes on papilla regeneration. METHODS: Thirty patients with single
      tooth implant-supported restorations in the anterior maxilla were assigned to two
      groups according to labial mucosa thickness. Group A: labial mucosal
      thickness>=1.5 mm and group B: labial mucosal thickness<1.5 mm. The presence of
      interproximal papilla as well as the distance between papilla apex and contact
      point were assessed at crown attachment (baseline) and after 6 months (follow
      up).Statistical analysis was performed using SPSS19.0 software package. RESULTS:
      The 6-month survival rate of implants was 100%. The mean height of interproximal
      papilla at baseline and follow-up was (1.64+/-0.97) mm and (3.10+/-1.39) mm,
      respectively. A significant improvement in papilla height was found between
      baseline and follow-up(P<0.05). In group A, the mean distance from papilla apex
      to the contact point at mesial and distal aspects was (0.15+/-0.24) mm and
      (0.23+/-0.33) mm, respectively, and the presence of interproximal papilla were
      (97+/-5)% and (94+/-8)%, respectively. In group B, the mean distance from papilla
      apex to the contact point at mesial and distal aspects was (1.94+/-0.40) mm and
      (2.10+/-0.34) mm, respectively, and the presence of interproximal papilla was
      (53+/-9)% and (43+/-14)% respectively. Statistically significant difference was
      found between the two groups(P<0.05). CONCLUSIONS: The interproximal papilla
      height around single implant restorations could improve significantly after 6
      month follow-up. The interproximal papilla height around single-tooth implants in
      the anterior maxilla was influenced by gingival biotype. The regenerative
      potential of thick-gingival biotype was better than that of thin-gingival
      biotype.

PMID- 23135186
TI  - [Expression and significance of Runx3 in salivary adenoid cystic carcinoma].
AB  - PURPOSE: To investigate the association between Runx3 expression and progression
      of salivary adenoid cystic carcinoma(SACC). METHODS: The expression of Runx3 was
      examined in 4 pairs of primary SACC and adjacent salivary gland tissues from the
      same patient, using real-time PCR and Western blot. Furthermore, the Runx3
      protein expression was analyzed in 65 clinicopathologically characterized SACC
      cases by immunohistochemistry. SPSS 17.0 software package was applied to complete
      data processing.Chi-square test was performed to determine the prognostic and
      diagnostic associations. RESULTS: Runx3 expression was found to be remarkably
      downregulated in SACC tissues than that in the normal salivary gland tissues, at
      both mRNA and protein levels. Statistical analysis revealed a significant
      correlation of Runx3 expression with Lymph node metastasis. CONCLUSIONS: The
      results suggest that Runx3 expression is associated with SACC progression, and
      might represent as a novel and valuable biomarker for clinical therapy of SACC
      patients.

PMID- 23135187
TI  - [Association between -590C/T polymorphisms of interleukin-4 gene and chronic
      periodontitis: a meta-analysis].
AB  - PURPOSE: To evaluate the relationship between -590C/T polymorphisms of
      interleukin-4 gene and chronic periodontitis using meta-analysis. METHODS: The
      selected studies were pooled from eight major electronic databases for case
      control study. To gain a more precise estimation of the relationship, a
      stratified meta-analysis with two subgroups was performed according to the races.
      Heterogeneity, publication bias and sensitivity analysis were also explored.
      RESULTS: Totally 8 studies were recruited. Total sample sizes for chronic
      periodontitis and control groups were 628 and 717, respectively. Meta-analysis
      showed that both -590C/T polymorphisms and allele frequency were not
      significantly associated with chronic periodontitis. In subgroup analysis, a
      significant association of increased chronic periodontitis risk and T allele was
      found. The results also indicated a significant correlation between -590C/T
      polymorphisms of IL-4 and Caucasian who suffered from chronic periodontitis(C
      vs.T: OR=0.71,95% CI=0.56-0.89;CC vs.CT:OR=0.60,95% CI=0.38-0.94;recessive
      genetic model CC vs.CT+TT:OR=0.61,95% CI=0.42-0.88), further analysis of the
      results showed the CC genotype was about 39% less likely to have chronic
      periodontitis than the CT and TT genotype in Caucasian individuals.However, these
      significant associations was not found in Asian group. CONCLUSIONS: The meta
      analysis suggests there may be an important effect of single nucleotide
      polymorphisms (SNPs) in the promoter region of IL-4 gene on the pathogenesis of
      chronic periodontitis in Caucasian. This warrants further investigation in larger
      studies and multi-race epidemiological to evaluate the results.

PMID- 23135188
TI  - [Prediction and assessment of facial profile after bimaxillary orthognathic
      surgery in skeletal Class III malocclusion].
AB  - PURPOSE: To predict and assess the facial profile after bimaxillary orthognathic
      surgery in a patient model. METHODS: One patient with skeletal Class III
      malocclusion was selected. The orthognathic surgery design was simulated through
      Photoshop CS4 software. Preoperative photograph and lateral cephalometric
      radiograph were processed to produce the first standard facial profile
      photography P1. The maxillary hard tissue was moved forward according to Andrews
      theory II, and soft tissue also moved in proportion until the mandible recessed
      to the Chinese G-Sn-Pog' angle .Then the mandible was moved forward and back +/
      1,+/-2,+/-3,+/-5,+/-7 mm, generating 20 facial profile photographs. Two groups of
      reviewer were chosen for evaluation:specialists (40 orthodontists),undergraduates
      (68 undergraduates from Chongqing Medical University).They were asked to rank the
      21 random profiles in descending order. The difference of the score of 21
      photographs given by two groups of reviewer was compared using Wilcoxon rank sum
      test with SPSS13.0 software package. RESULTS: The scores of 21 profile
      photographs were significantly different(P<0.05).Profile D3 was considered to be
      the most beautiful,followed by D2,D1,B1,A1,P1,C1,A2 and B2. C4,A5,B5 and C5 were
      not acceptable. The scores for each photograph given by the two groups of
      reviewer were not significantly different (P>0.05). CONCLUSIONS: The reviewers
      give different scores for 21 profiles. Straight profile is most beautiful,
      followed by profile with minor mandibular or chin retraction.Profiles with severe
      protrusion or retrusion is not acceptable.

PMID- 23135189
TI  - [Clinical effect of pit and fissure sealant used in combination with different
      etching adhesive and 3M-Z350 flowable resin on young permanent teeth].
AB  - PURPOSE: To compare the effect of different etching adhesive and flowable resin
      in deep pits and fissures of young permanent molars sealant technique. METHODS:
      Children aged 6-8 years old were included in the study. The split mouth design
      was used. The first permanent molars were randomly assigned into 2 experimental
      groups:A and B.The teeth in group A were sealed with flowable resin and self
      etching adhesive,while the teeth in group B were sealed with flowable resin and
      phosphate acid system. The children were followed up every year, and the sealants
      were observed and evaluated. SPSS13.0 software package was used for statistical
      analysis. RESULTS: After 1 year, 2 and 3 years,the retention rate of group A was
      significantly lower than that of group B(P<0.05),while group A had more caries
      than group B(P<0.05) except at 1-year. CONCLUSION: Self-etching adhesive and
      flowable resin doesn't have excellent clinical effect on caries prevention.

PMID- 23135190
TI  - [Observation of Carabelli's trait on permanent maxillary molars].
AB  - PURPOSE: To investigate the prevalence of the Carabelli's trait in a Chinese
      population. METHODS: Direct intraoral examination was conducted on 2758 Han
      Chinese people. The expression of Carabelli's trait was divided into 5 grades.
      Software SPSS 13.0 software package was used for statistical analysis. The trait
      frequency differences between two genders, between right and left sides were
      evaluated using Chi-square tests. Correlations in the presence of the trait
      between bilateral antimeric teeth and between first and second molars at the same
      side were determined by Kendall test. RESULTS: The trait frequency was 36.18%
      (40.73% of the males and 32.13% of females) for the first and 1.39% (1.82% in
      males and 0.99% in females) for the second molars by individual counting method.
      Sex difference was statistically significant for the first molars (P<0.01). The
      bilateral concurrence rate was 72.97% and 48.57% for the first and second molar,
      and the bilateral correlation coefficient tau was 0.77 and 0.65, respectively.
      The correlation between the first and second molar in the same teeth district was
      weak (tau=0.13, P<0.01). CONCLUSIONS: Evaluating the prevalence of Carabelli's
      trait in Chinese populations by using a standardized method has great
      anthropological significance.

PMID- 23135191
TI  - [Esthetic restoration for anterior teeth with the hot pressed porcelain laminate
      veneers].
AB  - PURPOSE: To evaluate the esthetic effect of anterior porcelain veneers fabricated
      with the heat pressed glass ceramic. METHODS: Thirty-two patients, who wanted to
      receive a aesthetic restorative treatment for 206 anterior teeth were selected.
      Among them, 20 were for dental fluorosis, 8 were for light tetracycline stained
      teeth, the other 4 were labial enamel hypoplasia or obvious crack on the surface
      of enamel. According to the color of adjacent teeth,skin and lips, heat pressed
      IPS e.max  ingots of different color were chosen to mold the restorations.
      Afterwards, special straining technique was conducted on the marginal ridge and
      incisor ridge of the veneers after carefully trimmed in the mouth. Restorations
      were them bonded with Variolink II resin cement. After 7 years of follow-up, a
      modified USPHS criterion was used to evaluate the esthetic effect. RESULTS: The
      translucency of veneers was superior. Marginal integrity of the veneers was
      perfect and it docked well with the marginal terminate line of the abutment.
      There was no edge coloring after the veneers were used for 7 years, and the
      veneers produce an excellent chameleon effect by absorbing the color of adjacent
      teeth and gums, at the same time, veneers could produce a feature of surface
      morphology of natural enamel after careful carve. In the long-term clinical
      observation, 5 of the 206 veneers were fractured or fell off. CONCLUSIONS: This
      porcelain laminate veneers fabricated from the heat pressed IPS e.max Press
      ingots include the following advantages, such as simple operating procedure, high
      mechanical strength, very little dental tissue was ground off and nice aesthetic
      effect. Ultra-thin veneers are especially suitable for aesthetic practice to
      dental fluorosis, light tetracycline and natural worn teeth.

PMID- 23135192
TI  - [Investigation of molar-incisor hypomineralization among children from 6 to 11
      years in Lucheng district, Wenzhou city].
AB  - PURPOSE: To investigate and analyze the prevalence and severity of molar-incisor
      hypomineralization(MIH) among children from 6 to 11 years old in Lucheng district
      of Wenzhou city. METHODS: Children aged 6 to 11 years (n=988) with all four-first
      permanent molars erupted were evaluated according to the European Academy of
      Paediatric Dentistry (EAPD) criteria. Examiners recorded the severity and
      position of each tooth diagnosed with MIH. SPSS 13.0 software package was used
      for analyze. Kruskal-Wallis test was used to determine the differences in the
      defect severity among different ages and the difference in the prevalence of MIH
      between the upper and lower molars or between the upper and lower incisors.
      Spearman test was used to test the association of the MIH-defect severity with
      the age of children. RESULTS: Molar-incisor hypomineralization was present in
      25.5% of the 988 children, and the majority of the defects presented were mild.
      There were significant differences among the six age groups with the severity of
      MIH (P<0.05), but no significant difference was found in the distribution of the
      MIH defect between the maxilla and the mandible (P>0.05). The severity of MIH
      increased along with the aging of children (rp=0.534). CONCLUSIONS: Despite the
      high prevalence of MIH, the severity of the defects was mild. The results
      indicate a positive association between the severity of MIH and the age of
      children.

PMID- 23135193
TI  - [The effect of two different methods of rapid maxillary expansion on treatment
      results of skeletal Class III malocclusion patients with maxillary protraction in
      early permanent dentition].
AB  - PURPOSE: To evaluate and compare the effect of single rapid maxillary expansion
      and repetitive rapid expansion and constriction with maxillary protraction in
      treating early permanent skeletal Class III patients. METHODS: Twenty children
      with skeletal Class III malocclusion were randomly divided into two groups.Ten
      patients received 1 week of rapid expansion,followed by maxillary
      protraction(group A) and the other ten patients received 5 weeks of repetitive
      rapid expansion and constriction followed by maxillary protraction (group
      B).Cephalometric analysis was performed before and after treatment. The data was
      analyzed with SPSS 13.0 software package for paired t test. RESULTS: Significant
      changes in cranio-maxillofacial structures were observed in both groups after 6
      months of treatment.Point A moved forward. SNA, ANB, UL-EP, U1-PP, SN-MP, ANS
      Me/N-Me, Wit's value increased. L1-MP, LL-EP decreased. Significant differences
      were found in SNA,ANB,UL-EP between the two groups(P<0.05). CONCLUSIONS: The
      application of combined repetitive rapid expansion and constriction with
      maxillary protraction increases the amount of forward movement of the maxilla
      significantly and presents more favourable profile results in early permanent
      Class III malocclusion patients.

PMID- 23135194
TI  - [Comparative study of two treatment methods for acute periodontal abscess].
AB  - PURPOSE: The aim of this short-term study was to compare the clinical efficacy of
      2 different methods to treat acute periodontal abscesses. METHODS: After patient
      selection, 100 cases of acute periodontal abscess were randomly divided into two
      groups. The experimental group was treated by supra- and subgingival scaling,
      while the control group was treated by incision and drainage. A clinical
      examination was carried out to record the following variables: subjective
      clinical variables including pain, edema, redness and swelling; objective
      clinical variables including gingival index(GI), bleeding index(BI), probing
      depth(PD),suppuration, lymphadenopathy and tooth mobility. The data was analyzed
      with SPSS 19.0 software package. RESULES: Subjective clinical variables
      demonstrated statistically significant improvements with both methods from the
      first day after treatment and lasted for at least 30 days(P<0.05), but the
      results of experimental group showed much better than the control group 1 day and
      7 days after treatment. 30 days after treatment, there was no significant
      difference between the two groups in pain and swelling improvement(P>0.05), but
      the experimental group showed more improvement in edema and redness than the
      control group(P<0.05).On improving objective variables, the experimental group
      showed significant improvement in GI,BI,PD and suppuration 1 day after
      treatment(P<0.05).After 7 days, all objective clinical variables in the
      experimental group improved significantly(P<0.05) in the control group, there
      were significant improvements in GI,suppuration,lymphadenopathy and tooth
      mobility(P<0.05) but the four variables of the experimental group showed more
      improvement than the control group(P<0.05).After 30 days, all objective clinical
      variables improved significantly in both groups as compared to baseline, but in
      the experimental group, improvements were more significant regarding to
      GI,BI,PD,suppuration and tooth mobility(P<0.05). CONCLUSION: The method of supra-
      and subgingival scaling was rapid and effective in treatment of acute periodontal
      abscesses.

PMID- 23135195
TI  - [Analysis of Shanghai residents' cognition and approbation to dental practical
      clinic].
AB  - PURPOSE: To know about Shanghai residents' cognition and approbation to dental
      practical clinic and discuss the appropriate mode of clinical teaching. METHODS:
      100 residents were chosen in five super-markets in five different districts
      randomly to fill in a questionnaire. RESULTS: 475 questionnaires were effective
      among 502 questionnaires and the efficiency was 94.62%; 10.32% informants knew
      the practical clinic, 56.84% informants would like to know it; 40.21% informants
      would like to choose the specialists, meanwhile 37.68% informants would choose
      the interns; 65.43% informants were satisfied with the dental interns.
      CONCLUSIONS: The cognition and approbation of residents to dental practical
      clinic should be enhanced, hospitals and schools should strengthen propaganda and
      improve teaching, in order to advancing the approbation based on upgrading the
      cognition.

PMID- 23135196
TI  - [Mandibular condyle ectomy for the treatment of comminuted condylar fracture].
AB  - PURPOSE: To investigate the feasibility and indication of condylectomy for
      treatment of comminuted fractures of the condyle above the neck. METHODS: Sixty
      one patients with condylar fractures, treated between September 2007 and
      September 2011 were reviewed respectively. Among them, 30 underwent open
      reduction and internal fixation, 15 underwent conservative therapy, and 16
      patients (18 sides) who had comminuted fractures of the condyle above the neck
      underwent condylectomy. All the patients were followed up for 5 to 48 months
      after treatment to evaluate the outcomes. RESULTS: Among the 16 patients with
      condylectomy, poor wound healing due to rejection of hemostatic gauze was noted
      in 1 patient, occlusal deviation occurred in 1 patient, mild mouth opening
      limitation happened in 1 patient, and anterior open bite was present in 1
      patient. The other patients recovered well, without apparent discomfort,
      malocclusion and facial asymmetry. CONCLUSIONS: For patients with finished
      maxillofacial growth, condylectomy is a feasible and effective way for management
      of comminuted fractures of the condyle above the neck. Postoperative occlusal
      deviation, open bite and limited mouth opening can be corrected with further
      expectant treatment.

PMID- 23135197
TI  - [Primary oncocytic carcinoma of the salivary glands: a clinical and pathologic
      study of 12 cases].
AB  - PURPOSE: To investigate the clinicopathological feature of oncocytic carcinoma of
      the salivary gland, and discuss diagnosis, treatment and prognosis. METHODS: From
      March 2001 to September 2010, the clinical data and pathological features of 12
      cases of oncocytic carcinoma of the salivary gland in Zhejiang Cancer Hospital
      were reviewed and analyzed retrospectively. All cases are followed up. The Kaplan
      Meier method was used to calculate survival curves by SPSS 16.0 software package.
      RESULTS: The tumors were found mainly as a painless, irregular-shaped mass or
      lymphadenectasis in the head and neck firstly. Pathologically, oncocytic
      carcinoma of salivary gland origin was an extremely rare proliferation of
      malignant oncocytes with adenocarcinomatous architectural phenotypes, including
      prominent nucleoli and infiltrative qualities. Surgery was the principal
      treatment, and postoperative radiotherapy was used as adjuvant treatment. Of the
      12 cases with follow-up for 6 to 120 months, 7 cases survived without regional or
      distant metastases. 1 case survived with regional and distant metastases. 2 cases
      died of regional recurrences.1 case had lymphatic metastasis and died of distant
      metastasis finally.1 case had given up therapy and died of tumor progress
      ultimately. 3 cases had local recurrence within 2 years, and the recurrence rate
      was 25%; 3 cases died within 2 years, and the mortality rate was 25%.
      CONCLUSIONS: Oncocytic carcinoma of salivary gland origin is an extremely rare
      tumor in head and neck, with short course and rapid progress. Radical resection
      postoperative radiotherapy is the treatment of choice. The prognosis of oncocytic
      carcinoma may be associated with tumor stage, regional lymph node metastases and
      complete surgical excision.

PMID- 23135198
TI  - Anatomy of the atlas and axis.

PMID- 23135199
TI  - Denosumab may reduce hypercalcaemia after transplantation for osteopetrosis.

PMID- 23135200
TI  - Low eGFR and high albuminuria predict end stage kidney disease and death at all
      ages.

PMID- 23135201
TI  - Should all advertising of cosmetic surgery be banned? Yes.

PMID- 23135202
TI  - Should all advertising of cosmetic surgery be banned? No.

PMID- 23135203
TI  - Introduction of ferrocene-containing [2]rotaxanes onto siloxane, silsesquioxane
      and polysiloxanes via click chemistry.
AB  - The reaction of N(3)(CH(2))(3)Si(OTMS)(3) (TMS = SiMe(3)) with a dialkylammonium
      having hexynyl group 1, [FcCH(2)NH(2)CH(2)C(6)H(4)-4-O(CH(2))(4)C=CH]PF(6) (Fc =
      Fe(C(5)H(4))(C(5)H(5))), in the presence of dibenzo[24]crown-8-ether (DB24C8) and
      [Cu{Fe(CN)(4)}]PF(6) catalyst yielded the [2]rotaxane containing the
      dialkylammonium unit terminated by a bulky silyl group. Azides with a
      silsesquioxane group react similarly to form the corresponding [2]rotaxanes
      having a bulky silsesquioxane end group. The azide-functionalized polysiloxane, [
      O-SiMe{(CH(2))(3)N(3)}-](n)[-O-SiMe(2)-](m) also undergoes a click reaction with
      1 to produce the side chain polyrotaxane. Cyclic voltammograms of these rotaxanes
      and 1 [(DB24C8)1] show the Fe(II)/Fe(III) redox at the same potential, but with
      different current depending on their molecular weights. Addition of
      PdCl(2)(MeCN)(2) to a solution of the side-chain polyrotaxane forms gel which
      regenerates the sol upon addition of PPh(3).

PMID- 23135204
TI  - Effects of exercise therapy on knee joint function and synovial fluid cytokine
      levels in patients with knee osteoarthritis.
AB  - The aims of this study were to observe the effect of exercise therapy on the
      function of the knee joint and the levels of cytokines and cytokine-related
      genes, specifically tumor necrosis factor-alpha (TNF-alpha), high sensitivity C
      reactive protein (hs-CRP) and matrix metalloproteinase-3 (MMP-3), in the synovial
      joints of patients with knee osteoarthritis (KOA) and to explore its mechanism of
      action. A total of 100 KOA patients were divided into a treatment group (n=50)
      and a control group (n=50) according to the order of admission. The patients in
      the treatment group were treated with diclofenac sodium combined with exercise
      therapy and the patients in the control group were treated with diclofenac sodium
      only. The function of the knee joint and the therapeutic efficacy was evaluated
      and the TNF-alpha, hs-CRP and MMP-3 levels in the synovial fluid were measured
      following 4 weeks of treatment. The results revealed that the knee joint index
      score and the TNF-alpha, hs-CRP and MMP-3 levels in the synovial fluid decreased
      significantly in the KOA patients of the two groups following treatment (P<0.05).
      Compared with the control group, the knee joint index score and the TNF-alpha, hs
      CRP and MMP-3 levels in the synovial joints were lower and the therapeutic
      efficacy was increased in the patients of the treatment group (P<0.05). In brief,
      exercise therapy may decrease cytokine and cytokine-related gene levels in the
      synovial fluid and inhibit inflammatory factor-mediated cartilage degradation in
      KOA patients, thus, effectively improving the clinical symptoms of KOA. 

PMID- 23135205
TI  - Increased expression of nitric oxide synthase interacting protein (NOSIP)
      following traumatic spinal cord injury in rats.
AB  - Previous studies indicated that nitric oxide (NO) is involved in secondary damage
      of spinal cord injury (SCI), which worsens the primary physical injury to the
      central nervous systems. Recently, nitric oxide synthase interacting protein
      (NOSIP) has been identified to interact with neuronal nitric oxide synthase
      (nNOS) and endothelial nitric oxide synthase by inhibiting the NO production.
      However, its expression and function after a central nervous system injury
      remains unclear. In this study, we examined the expression and cellular
      localization of NOSIP in the spinal cord of an adult rat. Western blot analysis
      indicated that NOSIP protein levels increased at day1 post-injury and peaked at
      day 14. Double immunofluorescence staining showed that NOSIP was primarily
      expressed in neurons and glial cells in the intact spinal cord. Interestingly,
      this study also showed that the expression of NOSIP significantly increased in
      astrocytes after injury. Furthermore, injury-induced expression of NOSIP was co
      expressed with proliferating cell nuclear antigen (PCNA) positive astrocytes
      after injury. We also showed the NOSIP was co-localized with nNOS in gray matter
      and white matter after SCI. All these data taken together suggested that NOSIP
      may play an important roles in astrogliogenesis after a spinal cord injury.

PMID- 23135207
TI  - A supramolecularly templated catenane initiator and a controlled ring expansion
      strategy.
AB  - We report the first synthesis of a catenated polymer via a ring-expansion
      strategy, which is based on a supramolecularly templated initiator. The high
      yielding synthesis and simple isolation method will enable the investigation and
      development of this unique polymer system for further applications.

PMID- 23135208
TI  - Efficacy and safety of loop diuretic therapy in acute decompensated heart
      failure: a clinical review.
AB  - Intravenous loop diuretics are widely used to treat the symptoms and signs of
      fluid overload in acute heart failure (AHF). Although diuretic therapy is widely
      used and strongly recommended by most recent clinical guidelines, prospective
      studies and randomized clinical trials are lacking and so reliable evidence is
      missing about the best therapy in terms of doses and methods of administration.
      In addition, clinical efficacy and safety outcomes are often affected by the
      presence of contrasting evidence. The efficacy of loop diuretics is impaired by
      diuretic resistance characterized by a decreased diuretic and natriuretic effect.
      This review focuses on the current management of AHF with diuretic therapy.
      Continuous diuretic infusion seems to be a good choice, from a pharmacokinetic
      point of view, when fluid overload is refractory to conventional therapy. Some
      available evidence comparing bolus injection to continuous infusion of loop
      diuretics proved the latter to be an effective and safe method of administration.
      Continuous infusion seems to produce a constant plasmatic concentration of drug
      with a more uniform daily diuretic and natriuretic effect and a greater safety
      profile (fewer adverse events such as worsening renal failure, electrolyte
      imbalances, ototoxicity). The analyses of the published studies did not provide
      conclusive data about the effects on clinical outcomes (mortality, rate of
      hospital readmissions, length of hospital stay and adverse events). Furthermore,
      recent studies focus their attention on alternative strategies of fluid removal,
      such as vasopressin antagonists, adenosine antagonists and ultrafiltration but
      available data are often inconclusive. 

PMID- 23135209
TI  - Combined use of transcranial magnetic stimulation and metal electrode implants: a
      theoretical assessment of safety considerations.
AB  - This paper provides a theoretical assessment of the safety considerations
      encountered in the simultaneous use of transcranial magnetic stimulation (TMS)
      and neurological interventions involving implanted metallic electrodes, such as
      electrocorticography. Metal implants are subject to magnetic forces due to fast
      alternating magnetic fields produced by the TMS coil. The question of whether the
      mechanical movement of the implants leads to irreversible damage of brain tissue
      is addressed by an electromagnetic simulation which quantifies the magnitude of
      imposed magnetic forces. The assessment is followed by a careful mechanical
      analysis determining the maximum tolerable force which does not cause
      irreversible tissue damage. Results of this investigation provide useful
      information on the range of TMS stimulator output powers which can be safely used
      in patients having metallic implants. It is shown that conventional TMS
      applications can be considered safe when applied on patients with typical
      electrode implants as the induced stress in the brain tissue remains well below
      the limit of tissue damage.

PMID- 23135210
TI  - MRP2 (ABCC2, cMOAT) expression in nuclear envelope of primary fallopian tube
      cancer cells is a new unfavorable prognostic factor.
AB  - OBJECTIVE: To determine the prognostic value of the immunohistochemical
      evaluation of the multidrug resistance-associated protein 2 (MRP2) expression,
      together with its subcellular localization in primary fallopian tube carcinomas
      (PFTCs). METHODS: The immunohistochemical analysis was performed using samples
      originating from 70 patients with PFTCs. RESULTS: (1) We documented that MRP2 can
      be localized in the plasma membrane (MRP2c), as well as in the nuclear envelope
      (MRP2n) of the PFTC cells. (2) Patients with more advanced stage, with
      progression of the disease and patients who died, showed significantly higher
      expression of the MRP2n. (3) Univariate and multivariate analyses showed that
      MRP2n is an unfavorable prognostic factor in PFTCs. (4) The analysis of the
      classic clinicopathological data revealed that only the FIGO stage had prognostic
      value, both in the univariate, as well as in multivariate analysis. CONCLUSIONS:
      (1) This study suggests that MRP2n is a new disadvantageous prognostic factor in
      PFTCs and (2) that expression in nuclear envelope can be associated with lower
      differentiation of cancer cells and their resistance to the cisplatin. (3) We
      have also confirmed independent prognostic value of FIGO stage in PFTCs.

PMID- 23135211
TI  - Neuropathic mechanisms in the pathophysiology of burns pruritus:  redefining
      directions for therapy and research.
AB  - Pruritus in burn wounds is a common symptom affecting patient rehabilitation.
      Over the last decades, there has been a resurgence of interest into more
      effective strategies to combat this distressing problem; nevertheless, no reports
      exist in the literature to propose pathophysiological mechanisms responsible for
      the generation and persistence of pruritic symptoms in the late phases of burns
      rehabilitation. Neuronal pathways mediating pruritic and painful stimuli share
      striking similarities, which allows the comparative exploration of the less
      extensively studied pruritic mechanisms using pain models. Furthermore, emerging
      anatomical, neurophysiological, and pharmacological evidence supports the
      involvement of neuropathic mechanisms in chronic burns pruritus. This work
      updates the conceptual framework for the pathophysiology of burns itch by
      embracing the contribution of the central nervous system in the maintenance of
      symptoms into a chronic state. The proposed pathophysiological model paves new
      avenues in burns pruritus research and is likely to have implications in the
      quest for more effective therapeutic regimens in clinical practice.

PMID- 23135212
TI  - Novel predictors of sepsis outperform the American Burn Association sepsis
      criteria in the burn intensive care unit patient.
AB  - The purpose of this study was to determine whether systemic inflammatory response
      syndrome (SIRS) and American Burn Association (ABA) criteria predict sepsis in
      the burn patient and develop a model representing the best combination of novel
      clinical sepsis predictors. A retrospective, case-controlled, within-patient
      comparison of burn patients admitted to a single intensive care unit from January
      2005 to September 2010 was made. Blood culture results were paired with
      documented sepsis: positive-sick, negative-sick (collectively defined as sick),
      and negative-not sick. Data for all predictors were collected for the 72 hours
      before blood culture. Variables were evaluated using regression and area under
      the curve (AUC) analyses. Fifty-nine subjects represented 177 culture periods.
      SIRS criteria were not discriminative: 98% of the subjects met criteria. ABA
      sepsis criteria were different on the day before (P = .004). The six best-fit
      variables identified for the model included heart rate > 130 beats per min, mean
      arterial pressure < 60 mm Hg, base deficit < -6 mEq/L, temperature < 36 degrees
      C, use of vasoactive medications, and glucose > 150 mg/dl. The model was
      significant in predicting positive-sick and sick, with an AUC of 0.775 (P < .001)
      and 0.714 (P < .001), respectively; comparatively, the ABA criteria AUC was 0.619
      (P = .028) and 0.597 (P = .035), respectively. Usefulness of the ABA criteria to
      predict sepsis is limited to the day before blood culture is obtained. A
      significant contribution of this research is the identification of six novel
      sepsis predictors for the burn patient.

PMID- 23135213
TI  - Strategies to increase flap survival in nasal reconstruction in patients with
      deep panfacial burns.
AB  - Total nasal reconstruction requires the management of skin, cartilage, and nasal
      mucosa. This three-dimensional surgical approach is especially restricted in
      patients with severe deformities after deep panfacial burns. In this regard, the
      development of tissue fibrosis reduces the quality and reliability of surrounded
      donor sites, limiting the surgical options and flap survival outcomes. This
      report discusses the benefit of tissue protection procedures, such as flap delay
      and leech therapy, in the total nasal reconstruction of a patient with split
      thickness skin grafts on donor sites for forehead and nasolabial flaps.

PMID- 23135214
TI  - Proliferation and apoptosis of peripheral blood mononuclear cells in patients
      with oral lichen planus.
AB  - Oral lichen planus (OLP) is generally accepted to be a T cell-mediated chronic
      inflammatory disease with an unclear pathogenesis. There have been numerous
      studies on the proliferation and apoptosis of T cells in situ. In contrast,
      research on the proliferation and apoptosis of peripheral blood mononuclear cells
      (PBMCs) in patients with OLP is rare. The aim of the present study was to
      investigate the proliferation and apoptosis of PBMCs in patients with OLP. PBMCs
      were isolated from 20 patients with reticular OLP, 20 patients with atrophic
      erosive OLP, and 20 healthy volunteers. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl
      2,5-tetrazolium bromide assays were performed to investigate the proliferation of
      PBMCs, and caspase-3 colorimetric assays were performed to investigate the
      apoptosis of PBMCs. The proliferation rate of PBMCs in atrophic-erosive OLP
      subjects was significantly higher than that in both healthy (P < 0.05) and
      reticular OLP (P < 0.05) subjects. In contrast, the proliferation rate of PBMCs
      in reticular OLP subjects was significantly lower than that in healthy subjects
      (P < 0.05). The apoptosis rates of PBMCs in OLP subjects (P < 0.05) and atrophic
      erosive OLP subjects (P < 0.05) were significantly lower than the apoptosis rate
      in the healthy group. Our findings reinforce the view that T cell-mediated immune
      responses play a critical role in the pathogenesis of OLP. It can reasonably be
      concluded that these abnormalities are linked to the presence of inflammatory
      infiltrates.

PMID- 23135215
TI  - Towards a more cloud-friendly medical imaging applications architecture: a modest
      proposal.
AB  - Recent information technology literature, in general, and radiology trade
      journals, in particular, are rife with allusions to the "cloud" suggesting that
      moving one's compute and storage assets into someone else's data center magically
      solves cost, performance, and elasticity problems. More likely, one is only
      trading one set of problems for another, including greater latency (aka slower
      turnaround times) since the image data must now leave the local area network and
      travel longer paths via encrypted tunnels. To offset this, an imaging system
      design is needed that reduces the number of high-latency image transmissions, yet
      can still leverage cloud strengths. This work explores the requirements for such
      a design.

PMID- 23135217
TI  - Risk-to-benefit ratio of inhaled corticosteroids in patients with COPD.
AB  - While the pharmacological management of chronic obstructive pulmonary disease
      (COPD) has evolved from the drugs used to treat asthma, the treatment models are
      different and the two diseases require clear differential diagnosis in order to
      determine the correct therapeutic strategy. In contrast to the almost universal
      requirement for anti-inflammatory treatment of persistent asthma, the efficacy of
      inhaled corticosteroids (ICS) is less well established in COPD and their role in
      treatment is limited. There is some evidence of a preventive effect of ICS on
      exacerbations in patients with COPD, but there is little evidence for an effect
      on mortality or lung function decline. As a result, treatment guidelines
      recommend the use of ICS in patients with severe or very severe disease (forced
      expiratory volume in 1 second <50% predicted) and repeated exacerbations.
      Patients with frequent exacerbations - a phenotype that is stable over time - are
      likely to be less common among those with moderate COPD (many of whom are managed
      in primary care) than in those with more severe disease. The indiscriminate use
      of ICS in COPD may expose patients to an unnecessary increase in the risk of side
      effects such as pneumonia, osteoporosis, diabetes and cataracts, while wasting
      healthcare spending and potentially diverting attention from other more
      appropriate forms of management such as pulmonary rehabilitation and maximal
      bronchodilator use. Physicians should carefully weigh the likely benefits of ICS
      use against the potential risk of side-effects and costs in individual patients
      with COPD.

PMID- 23135218
TI  - Acceptability and feasibility of pulmonary rehabilitation for  COPD: a community
      qualitative study.
AB  - BACKGROUND: Pulmonary rehabilitation (PR) is second in importance to smoking
      cessation treatment in the management of chronic  obstructive pulmonary disease
      (COPD). Access to the service is limited and less than half of those referred
      complete the treatment. AIMS: We assessed the obstacles to participation in PR
      among COPD patients in a community-based PR programme and associated  general
      practices. METHODS: A qualitative interview study was conducted among COPD
      patients who completed the PR treatment, those who did not  complete or declined
      treatment, and patients never referred. Participants were invited by letter from
      their own general practitioners or  from the PR service. Views on exercise,
      disease education, social contact, group activity, accessibility, location, role
      of referrer, and support  for participation were assessed. Data were analysed
      using the framework approach. RESULTS: Twenty-four patients (28%, 13 male, 12 not
      referred) were interviewed. The acceptability of PR was the major concern.
      Feasibility  of attending was an issue for some. Perceptions of PR and of
      exercise were highlighted. How a smoker might be seen, the suitability of  group
      activity, and the views of professionals were influential, as were positive and
      negative recommendations. The location of the centre  was important.
      Participants' willingness or reluctance to take on something new was a central
      element of the decision. Many would  welcome the role of experienced patients in
      introducing the treatment. CONCLUSIONS: For patients who refused referral to PR,
      had not completed a course, or had yet to be referred, the way the service was 
      introduced was an important determinant of willingness to participate.

PMID- 23135219
TI  - Application of a NotI subtraction and methylation-specific genome subtractive
      hybridization technique in the detection of genomic DNA methylation differences
      between hydatidiform moles and villi.
AB  - Previous studies indicate that epigenetic modifications play an important role in
      transcriptional regulation and contribute to the pathogenesis of gestational
      trophoblastic disease, including complete hydatidiform moles (CHMs). However, the
      underlying mechanisms and the critical genes have not been clearly identified. In
      the present study, we developed a novel technique, NotI subtraction and
      methylation-specific genome subtractive hybridization (MS-G-SH), as a method of
      screening for methylation changes between hydatidiform moles and villi. Following
      NotI subtraction and hybridization, three different positive DNA clones were
      found in 110 random clones of DNA samples. Most importantly, two DNA clones
      having long CpG islands and high homology with exons of insulin-like growth
      factor 2 (IGF2) and transforming growth factor-beta (TGF-beta) were identified
      using bioinformatic tools. After bisulfite treatment and methylation-specific
      PCR, the specific methylation of certain exons of IGF2 and TGF-beta was
      identified. In addition, the mRNA expression levels of these two genes were
      markedly different. In conclusion, this novel MS-G-SH technique is an alternative
      and effective approach for the detection of specific DNA methylation. 

PMID- 23135220
TI  - One-pot mechanosynthesis of aromatic amides and dipeptides from carboxylic acids
      and amines.
AB  - Environmentally friendly one-pot synthesis of amides, bis-amides and dipeptides
      by mechanochemical carbodiimide-mediated coupling of carboxylic acids and amines
      is described; high reaction yields and simple aqueous work-up allow for the
      clean, practical and fast preparation of a variety of compounds containing the
      amide bond from readily accessible reagents.

PMID- 23135221
TI  - Pioglitazone and risk of bladder cancer: clarification of the design of the
      French study.

PMID- 23135222
TI  - Towards microRNA-based therapeutics for diabetic nephropathy.
AB  - There is no cure for diabetic nephropathy and the molecular mechanisms underlying
      disease aetiology remain poorly understood. While current paradigms for clinical
      management of diabetic nephropathy are useful in delaying disease onset and
      preventing its progression, they do not do so for a significant proportion of
      diabetic individuals, who eventually end up developing renal failure. Thus, novel
      therapeutic targets are needed for the treatment and prevention of the disease.
      MicroRNAs (miRNAs), a class of non-coding RNAs that negatively regulate gene
      expression, have recently been identified as attractive targets for therapeutic
      intervention. It is widely recognised that dysregulation of miRNA expression or
      action contributes to the development of a number of different human diseases,
      and evidence of a role for miRNAs in the aetiology of diabetic nephropathy is
      emerging. The discovery that modulation of miRNA expression in vivo is feasible,
      combined with recent results from successful clinical trials using this
      technology, opens the way for future novel therapeutic applications. For
      instance, inhibition of miRNAs that are commonly upregulated in diabetic
      nephropathy decreases albuminuria and mesangial matrix accumulation in animal
      models, suggesting that a therapeutic agent against these molecules may help to
      prevent the development of diabetic nephropathy. Certain challenges, including
      the development of safe and reliable delivery systems, remain to be overcome
      before miRNA-based therapeutics become a reality. However, the findings
      accumulated to date, in conjunction with newly emerging results, are expected to
      yield novel insights into the complex pathogenesis of diabetic nephropathy, and
      may eventually lead to the identification of improved therapeutic targets for
      treatment of this disease.

PMID- 23135223
TI  - Let's keep clinical breast examination until the breast service is reconfigured.

PMID- 23135224
TI  - Glycine reduces platelet aggregation.
AB  - It has been demonstrated that a wide variety of white blood cells and macrophages
      (i.e. Kupffer cells, alveolar and peritoneal macrophages and neutrophils) contain
      glycine-gated chloride channels. Binding of glycine on the receptor stimulates
      Cl(-) influx causing membrane hyperpolarization that prevents agonist-induced
      influx of calcium. Since platelet-aggregation is calcium-dependent, this study
      was designed to test the hypothesis that glycine would inhibit platelet
      aggregation. Rats were fed diets rich of glycine for 5 days, while controls
      received isonitrogenous valine. The bleeding time and ADP- and collagen-induced
      platelet aggregation were measured. Dietary glycine significantly increased
      bleeding time about twofold compared to valine-treated controls. Furthermore, the
      amplitude of platelet aggregation stimulated with ADP or collagen was
      significantly decreased in whole blood drawn from rats fed 2.5 or 5 % dietary
      glycine by over 50 %. Addition of glycine in vitro (1-10 mM) also blunted rat
      platelet aggregation in a dose-dependent manner. Strychnine, a glycine receptor
      antagonist, abrogated the inhibitory effect of glycine on platelet-aggregation in
      vitro suggesting the glycine works via a glycine receptor. Glycine also blunted
      aggregation of human platelets. Further, the glycine receptor was detected in
      both rat and human platelets by western blotting. Based on these data, it is
      concluded that glycine prevents aggregation of platelets in a dose-dependent
      manner via mechanisms involving a glycine receptor.

PMID- 23135225
TI  - Vaspin attenuates the apoptosis of human osteoblasts through ERK signaling
      pathway.
AB  - It has been hypothesized that adipocytokines originating from adipose tissue may
      have an important role in bone metabolism. Vaspin is a novel adipocytokine
      isolated from visceral white adipose tissue, which has been reported to have anti
      apoptotic effects in vascular endothelial cells. However, to the best of our
      knowledge there is no information regarding the effects of vaspin on osteoblast
      apoptosis. This study therefore examined the possible effects of vaspin on
      apoptosis in human osteoblasts (hOBs). Our study established that vaspin inhibits
      hOBs apoptosis induced by serum deprivation, as determined by ELISA and TUNEL
      assays. Western blot analysis revealed that vaspin upregulates the expression of
      Bcl-2 and downregulates that of Bax in a dose-dependent manner. Vaspin stimulated
      the phosphorylation of ERK, and pretreatment of hOBs with the ERK inhibitor
      PD98059 blocked the vaspin-induced activation of ERK, however, vaspin did not
      stimulate the phosphorylation of p38, JNK or Akt. Vaspin protects hOBs from serum
      deprivation-induced apoptosis, which may be mediated by activating the MAPK/ERK
      signaling pathway.

PMID- 23135226
TI  - Combination of BCAAs and glutamine enhances dermal collagen protein synthesis in
      protein-malnourished rats.
AB  - Skin collagen decreases in protein-malnourished states. Amino acids regulate
      protein metabolism, glutamine stimulates collagen synthesis through the
      conversion process to proline and provides 75 % of the intracellular free proline
      in fibroblasts. However, the impact of these amino acids on collagen synthesis
      under malnutrition has not been examined. We investigated the effect of amino
      acids on dermal tropocollagen synthesis in protein-malnourished rats. The
      fractional synthesis rate (FSR, %/h) of dermal tropocollagen was evaluated by the
      incorporation of L-[ring-(2)H(5)]-phenylalanine after 4 h infusion of each amino
      acid and the stable isotope. None of the infused 12 single amino acids
      (glutamine, proline, alanine, arginine, glutamate, glycine, aspartate, serine,
      histidine, lysine, phenylalanine and threonine) significantly increased the FSR
      (P = 0.343, one-way ANOVA). In contrast, amino acid mixtures of essential amino
      acids + glutamine + arginine (EAARQ) and branched-chain amino acids + glutamine
      (BCAAQ) significantly increased the FSR compared to saline, but the branched
      chain amino acids (BCAAs) and amino acid mixture of collagen protein (AAC) did
      not alter the FSR (saline, 0.96 +/- 0.24 %/h; EAARQ, 1.76 +/- 0.89 %/h; BCAAQ
      1.71 +/- 0.36 %/h; BCAAs, 1.08 +/- 0.20 %/h and AAC 1.39 +/- 0.35 %/h, P < 0.05,
      Tukey's test). Proline conversion from glutamine represented only 3.9 % of the
      free proline in skin, as evaluated by the primed-constant infusion of L-d7
      proline and L-alpha-15N-glutamine in rats. These results suggested that the
      combination of BCAAQ is a key factor for the enhancement of skin collagen
      synthesis in protein-malnourished rats. The contribution of extracellular free
      glutamine on de novo proline synthesis and collagen synthesis is very low in vivo
      compared to the contribution in vitro.

PMID- 23135227
TI  - GeoChip-based analysis of the functional gene diversity and metabolic potential
      of soil microbial communities of mangroves.
AB  - Mangroves are unique and highly productive ecosystems and harbor very special
      microbial communities. Although the phylogenetic diversity of sediment microbial
      communities of mangrove habitats has been examined extensively, little is known
      regarding their functional gene diversity and metabolic potential. In this study,
      a high-throughput functional gene array (GeoChip 4.0) was used to analyze the
      functional diversity, composition, structure, and metabolic potential of
      microbial communities in mangrove habitats from mangrove national nature reserves
      in China. GeoChip data indicated that these microbial communities were
      functionally diverse as measured by the number of genes detected, unique genes,
      and various diversity indices. Almost all key functional gene categories targeted
      by GeoChip 4.0 were detected in the mangrove microbial communities, including
      carbon (C) fixation, C degradation, methane generation, nitrogen (N) fixation,
      nitrification, denitrification, ammonification, N reduction, sulfur (S)
      metabolism, metal resistance, antibiotic resistance, and organic contaminant
      degradation. Detrended correspondence analysis (DCA) of all detected genes showed
      that Spartina alterniflora (HH), an invasive species, did not harbor
      significantly different microbial communities from Aegiceras corniculatum (THY),
      a native species, but did differ from other species, Kenaelia candel (QQ),
      Aricennia marina (BGR), and mangrove-free mud flat (GT). Canonical correspondence
      analysis (CCA) results indicated the microbial community structure was largely
      shaped by surrounding environmental variables, such as total nitrogen (TN), total
      carbon (TC), pH, C/N ratio, and especially salinity. This study presents a
      comprehensive survey of functional gene diversity of soil microbial communities
      from different mangrove habitats/species and provides new insights into our
      understanding of the functional potential of microbial communities in mangrove
      ecosystems. 

PMID- 23135228
TI  - Isolation and characterization of protective anti-LPS nanobody against V.
      cholerae O1 recognizing Inaba and Ogawa serotypes.
AB  - Vibrio cholerae is considered one of the major health threats in developing
      countries. Lack of efficient vaccine, short incubating time of the disease, and
      bacterium ability to survive in aquatic environment have made cholera one of the
      most epidemic diseases yet known. The lipopolysaccharide is one of the bacterium
      key antigens used to classify V. cholerae into 206 serogroups. V. cholerae
      serogroup O1 is a causative agent of all cholera pandemics. Research has shown
      that anti-lipopolysaccharide (LPS) antibodies could provide protective immunity
      in cholera cases. In this research, we used N-terminal fragments of the camel's
      heavy-chain antibodies called VHH or nanobodies and produced a phagemid library.
      The obtained library was panned against V. cholerae O1 LPS, and four monoclonal
      nanobodies were isolated. Isolated nanobodies were tested in LPS ELISA and
      bacterial ELISA. The nanobody with the highest affinity toward the bacterium was
      used in an in vivo challenge and successfully neutralized the bacterium
      infection. The isolated nanobody showed high thermostability and proteolytic
      resistance in characterization tests.

PMID- 23135229
TI  - Progress in the research of S-adenosyl-L-methionine production.
AB  - This minireview mainly aims at the study of S-adenosyl-L-methionine (SAM)
      production by microbial fermentation. A brief introduction of the biological role
      and application of SAM was presented. In general, SAM production can be improved
      by breeding of the producing strain through the conventional mutation or genetic
      engineering approach in the molecular or cellular scale, by optimization of
      culture conditions in the cellular scale or bioreactor engineering scale, or by
      multiscale approach. The productivity of SAM fermentation has been improved
      greatly through the efforts of many researchers using the methods previously
      mentioned. The SAM-producing strains used extensively are Pichia pastoris and
      Saccharomyces cerevisiae. The effect of SAM on antibiotic production was also
      exemplified. The skill and scheme beneficial to the improvement of SAM production
      involves the enhancement of SAM synthetase (methionine adenosyltransferase)
      activity and selection of engineered constitutive promoters with appropriate
      strength; seeking for and eliminating the rate-limiting factors in SAM synthesis,
      namely, knocking off the genes that transform SAM and L-methionine (L-Met) to
      cysteine; release the feedback inhibition of SAM to methylenetetrahydrofolate
      reductase; blocking the transsulfuration pathway by interfering the responsible
      enzymes; enhancing ATP level through pulsed feeding of glycerol; and optimizing
      the L-Met feeding strategy. Precise control of gene expression and quantitative
      assessment of physiological parameters in engineered P. pastoris were
      highlighted. Finally, a discussion of the prospect of SAM production was
      presented.

PMID- 23135230
TI  - Multiple cavitary lesions in lungs.

PMID- 23135231
TI  - Looking beyond the test.

PMID- 23135232
TI  - The history of human populations in the Japanese Archipelago inferred from genome
      wide SNP data with a special reference to the Ainu and the Ryukyuan populations.
AB  - The Japanese Archipelago stretches over 4000 km from north to south, and is the
      homeland of the three human populations; the Ainu, the Mainland Japanese and the
      Ryukyuan. The archeological evidence of human residence on this Archipelago goes
      back to >30 000 years, and various migration routes and root populations have
      been proposed. Here, we determined close to one million single-nucleotide
      polymorphisms (SNPs) for the Ainu and the Ryukyuan, and compared these with
      existing data sets. This is the first report of these genome-wide SNP data. Major
      findings are: (1) Recent admixture with the Mainland Japanese was observed for
      more than one third of the Ainu individuals from principal component analysis and
      frappe analyses; (2) The Ainu population seems to have experienced admixture with
      another population, and a combination of two types of admixtures is the unique
      characteristics of this population; (3) The Ainu and the Ryukyuan are tightly
      clustered with 100% bootstrap probability followed by the Mainland Japanese in
      the phylogenetic trees of East Eurasian populations. These results clearly
      support the dual structure model on the Japanese Archipelago populations, though
      the origins of the Jomon and the Yayoi people still remain to be solved.

PMID- 23135233
TI  - Stability-indicating RP-HPLC method for the simultaneous determination of
      escitalopram oxalate and clonazepam.
AB  - The objective of the current study was to develop a validated, specific stability
      indicating reversed-phase liquid chromatographic (LC) method for the quantitative
      determination of escitalopram oxalate and clonazepam and their related substances
      in bulk drugs and pharmaceutical dosage forms in the presence of degradation
      products. Forced degradation studies were performed on the pure drugs of
      escitalopram oxalate and clonazepam, as per the stress conditions prescribed by
      the International Conference on Harmonization (ICH) using acid, base, oxidation,
      thermal stress and photolytic degradation to show the stability-indicating power
      of the method. Significant degradation was observed during acid and alkaline
      hydrolysis and no degradation was observed in other stress conditions. The
      chromatographic method was optimized using the samples generated from forced
      degradation studies. Good resolution between the peaks corresponded to the active
      pharmaceutical ingredients, escitalopram oxalate and clonazepam, and degradation
      products from the analyte were achieved on an ODS Hypersil C18 column (250 * 4.6
      mm) using a mobile phase consisting of a mixture of acetonitrile-50 mM phosphate
      buffer + 10 mM triethylamine (70:30, v/v). The detection was conducted at 268 nm.
      The limit of detection and the limit of quantitation for escitalopram oxalate and
      clonazepam were established. The stress test solutions were assayed against the
      qualified working standards of escitalopram oxalate and clonazepam, which
      indicated that the developed LC method was stability-indicating. Validation of
      the developed LC method was conducted as per ICH requirements. The developed LC
      method was found to be suitable to check the quality of bulk samples of
      escitalopram oxalate and clonazepam.

PMID- 23135234
TI  - Unexpected photostability improvement of aromatics in polyfluorinated solvents.
AB  - The photostability of aromatic compounds in the presence of air is significantly
      improved through perfluoroalkylation of the corresponding aromatic cores and use
      of polyfluorinated solvents despite higher O(2) concentration in polyfluorinated
      solvents than in hydrocarbon solvents.

PMID- 23135235
TI  - Influence of asthma on quality of life and clinical characteristics of patients
      with nasal polyposis.
AB  - Recent studies have evidenced that nasal polyposis (NP) may lead to significant
      limitations in physical, emotional and social aspects of life of the affected
      patients. The study is aimed to investigate the influence of asthma on quality of
      life (QoL), intensity of symptoms, endoscopic and computerized tomography (CT)
      sinus findings in patients with NP. The cross-sectional study included 88 adult
      patients with NP out of whom 35 (39.8 %) were asthmatic while 53 (60.2 %) were
      non-asthmatic. QoL is assessed based on Short Form-36 Health Survey (SF-36)
      questionnaire, while symptom intensity was presented using visual analogue scale
      (VAS). The objective finding is presented as endoscopic and CT score. Comparison
      of individual symptom intensity, total score and major symptom score failed to
      evidence any statistically significant difference between the groups. Minor
      symptom score which include intensity of headache, fetor ex ore, fatigue/malaise,
      dental pain, cough, pressure/fullness in the ears and fever was higher in the
      group with asthma (p < 0.05). Comparison of scores according to SF-36 domains, as
      well as summary scores for physical and mental health did not reveal
      statistically significant difference between the observed groups. Mean value of
      the endoscopic score in the group with asthma was 8.57 +/- 2.22, being 8.38 +/-
      1.93 in the group without asthma (p > 0.05). Mean value of the CT score in the
      groups with and without asthma was 20.37 +/- 4.34 and 17.47 +/- 4.75,
      respectively (p < 0.01). Asthma has no influence on QoL and endoscopic findings
      of patients with NP, however it influences minor symptom score and CT findings.

PMID- 23135236
TI  - Clinical evaluation of balloon dilation Eustachian tuboplasty in the Eustachian
      tube dysfunction.
AB  - The development of minimally invasive procedures such as the balloon dilation
      Eustachian tuboplasty (BET) is an alternative to the grommet tympanum membrane.
      BET is applied in the cases where, after elimination of all factors influencing
      the ET and middle ear functioning, no sufficient improvement is observed. The aim
      of this study was to present the therapeutic benefits of the BET method in the
      treatment of ETD caused by disorders in the middle ear ventilation. The BET
      procedure was offered to four patients (3 men and 1 woman) after subjective,
      physical, otorhinolaryngological and audiometric examinations including pure tone
      audiometry, tympanometry and pressure-swallow test. As the method was novel,
      preinterventional CT angiography of the carotid arteries was performed in all
      patients. Any complications were noticed during and after the procedure (bleeding
      or damage of regional mucosa) in any patients. Our clinical studies assessed the
      feasibility and safety of the BET during a short-term period--only a 6-week
      observation. Although patients revealed a significant improvement of ET score,
      longer long-term studies are necessary to determine whether this method will
      demonstrate lasting benefits and safety in the treatment of chronic Eustachian
      tube dysfunction. In other investigations, improvement was found to be time
      dependent.

PMID- 23135237
TI  - Management of growing vestibular schwannomas.
AB  - Conservative management of small vestibular schwannomas is frequently proposed as
      most tumours do not grow. Anyway, tumour growth is reported in 30-40 % of the
      cases, so that surgery is consequently generally proposed. We primarily observed
      161 patients affected by unilateral vestibular schwannomas. All patients were
      examined by means of gadolinium-enhanced magnetic resonance imaging scans. Tumour
      growth was recorded in 58 cases (35.8 %) and these subjects set up the group of
      study. Twenty-two (37.9 %) patients were surgically treated; tumour was always
      completely removed, all patients had normal facial function after surgery and
      only one patient suffered from a major complication (cerebellar haematoma).
      Fourteen patients (24.1 %) were submitted to radiotherapy, while one patient was
      lost at follow-up and another one died because of other medical reasons. Finally,
      20 (34.5 %) subjects continued to be observed for different reasons. The mean
      follow-up period after identification of growth was 6.1 years. Nine tumours
      continued to grow, nine tumours stopped growing, one tumour grew and then
      regressed in size and one tumour decreased. Sixty percent of patients with useful
      hearing at diagnosis preserved it during the entire observation period. In
      conclusion, most of VS do not grow; in case of tumour growth, a surgical
      procedure may be suggested and the outcomes are not negatively influenced by the
      delay of the procedure. But in some cases, patients can still follow the "wait
      and scan" policy. In fact, only less than half of the growing tumours continued
      to grow. Moreover, most of the patients continued to retain a useful hearing.

PMID- 23135238
TI  - The retrospective binning method improves the consistency of phase binning in
      respiratory-gated PET/CT.
AB  - This study assesses the accuracy of prospective phase-gated PET/CT data binning
      and presents a retrospective data binning method that improves image quality and
      consistency. Respiratory signals from 17 patients who underwent 4D PET/CT were
      analysed to evaluate the reproducibility of temporal triggers used for the
      standard phase-based gating method. Breathing signals were reprocessed to
      implement retrospective PET data binning. The mean and standard deviation of time
      lags between automatic triggers provided by the Real-time Position Management
      (RPM, Varian) gating device and inhalation peaks derived from respiratory curves
      were computed for each patient. The total number of respiratory cycles available
      for 4D PET/CT according to the binning mode (prospective versus retrospective)
      was compared. The maximum standardized uptake value (SUV(max)), biological tumour
      volume (BTV) and tumour trajectory measures were determined from the PET/CT
      images of five patients. Compared to retrospective binning (RB), prospective
      gating approach led to (i) a significant loss in breathing cycles (15%) and (ii)
      the inconsistency of data binning due to temporal dispersion of triggers (average
      396 ms). Consequently, tumour characterization could be impacted. In
      retrospective mode, SUV(max) was up to 27% higher, where no significant
      difference appeared in BTV. In addition, prospective mode gave an inconsistent
      spatial location of the tumour throughout the bins. Improved consistency with
      breathing patterns and greater motion amplitude of the tumour centroid were
      observed with retrospective mode. The detection of the tumour motion and
      trajectory was improved also for small temporal dispersion of triggers. This
      study shows that the binning mode could have a significant impact on 4D PET
      images. The consistency of triggers with breathing signals should be checked
      before clinical use of gated PET/CT images, and our RB method improves 4D PET/CT
      image quantification.

PMID- 23135239
TI  - An impression cytology based study of ocular surface in an urban population.
AB  - To assess the health of ocular surface in a defined urban population,
      conjunctival goblet cell density and degree of surface squamous metaplasia were
      utilized as study tools. Two thousand names of those aged between 20 and 79 years
      from the 2006 electoral register in ward number 63 of Kolkata Corporation area
      were initially selected. Normal healthy human volunteers without any history of
      ocular surface disorder were recruited and divided into five age-groups.
      Impression cytology samples were obtained from interpalpebral part of bulbar
      conjunctiva from all the participants fixated and stained by a single observer. A
      stratified, clustered, disproportionate, random sampling method was used. The
      software used in the statistical analysis was EPI Info. The tests applied were t
      test and ANOVA. A variation in the number of goblet cells according to gender
      (women having less cells) and age (20-30 years group having the highest number of
      cells) was found. Those working outdoors were found to have fewer goblet cells
      compared to those who stay indoors. The majority of the people had grade 1
      cytological appearance in both males and females. There was no statistically
      significant difference in Nelson's grading with age. People using coal and
      kerosene to cook were found to have a smaller goblet cell density than those who
      cooked on LPG or those who did not cook at all. Besides age and sex,
      environmental factors like the method of cooking and occupational variables (like
      outdoor activity, prolonged period of computer use, etc.) modify the health of
      the ocular surface. The results of this study will help put these findings into
      perspective as public health problems.

PMID- 23135240
TI  - Catecholamine receptors differentially mediate impulsive choice in the medial
      prefrontal and orbitofrontal cortex.
AB  - Impulsivity is characteristic of several mental health disorders and is largely
      mediated by the prefrontal cortex subregions: the medial prefrontal cortex (mPFC)
      and the orbitofrontal cortex (OFC). Dopamine (DA) and norepinephrine (NE) are
      known to modulate activity of the prefrontal cortex, however their direct role in
      impulsive choice is not known. The aim of the present study was to investigate
      the effect of microinjecting DA or NE compounds in the mPFC or OFC on impulsive
      choice as measured by a delayed reinforcement (DR) task in male Wistar Kyoto
      rats. Following training in the DR task, rats were pretreated with DA D(1) and
      D(2) receptor antagonists (SCH23390 3 MUg/side, raclopride 3 or 6 MUg/side) or NE
      alpha(1) and alpha(2) receptor agonists (phenylephrine 0.1 or 0.3 MUg/side,
      guanfacine 1 or 3 MUg/side, respectively) into the mPFC or OFC and the effect on
      impulsive behavior was assessed. Pretreatment with raclopride into the mPFC or
      OFC significantly increased impulsive choice, however only pretreatment with
      SCH23390 into the mPFC, and not the OFC, significantly increased impulsive
      choice. Pretreatment with the NE receptor agonists had no effect on impulsive
      choice. This study suggests that DA receptors, but not NE receptors,
      differentially mediate impulsive choice in sub-regions of the prefrontal cortex.

PMID- 23135241
TI  - Investigating the roles of different monoamine transmitters and impulse control
      using the 5-choice serial reaction time task.
AB  - Previous studies have shown that drugs which block the reuptake of catecholamine
      neurotransmitters improve impulse control in diseases such as attention deficit
      hyperactivity disorder (ADHD). Serotonin-specific reuptake inhibitors (SSRI) lack
      efficacy in ADHD and have been linked to increased suicide risk. The present
      study investigated drugs with affinity for one or more of the monoamine reuptake
      transporters using the 5-choice serial reaction time task, a model of attention
      and impulsivity in rodents. We also tested the effects of the alpha(2)
      adreoceptor antagonist, idazoxan and novel antidepressant, agomelatine, which
      both increase cortical noradrenaline concentrations through non-reuptake
      mechanisms. Improvements in impulse control were observed with venlafaxine, a
      serotonin and noradrenaline re-uptake inhibitor (SNRI) but not bupropion
      (dopamine and noradrenaline re-uptake inhibitor). Sibutramine (SNRI) reduced
      premature responses by ~50% at the highest dose tested but this was not
      significant. All three of the SSRIs tested reduced premature responding in a dose
      dependent manner, although also slowed response and collection latencies. Neither
      idazoxan nor agomelatine significantly reduced premature responding, suggesting a
      lack of efficacy at the doses tested. None of the drugs tested improved attention
      in this task but sibutramine (SNRI), fluoxetine (SSRI) and paroxetine (SSRI) all
      increased omissions at the highest dose tested. These data suggest that the SNRIs
      and SSRIs reduce premature responding but tend to be less specific than
      noradrenaline specific reuptake inhibitors in this model. SSRIs did not induce
      any specific impairment in impulse control in this model.

PMID- 23135248
TI  - Modelling emergence of oscillations in communicating bacteria: a structured
      approach from one to many cells.
AB  - Population-level measurements of phenotypic behaviour in biological systems may
      not necessarily reflect individual cell behaviour. To assess qualitative changes
      in the behaviour of a single cell, when alone and when part of a community, we
      developed an agent-based model describing the metabolic states of a population of
      quorum-coupled cells. The modelling is motivated by published experimental work
      of a synthetic genetic regulatory network (GRN) used in Escherichia coli cells
      that exhibit oscillatory behaviour across the population. To decipher the
      mechanisms underlying oscillations in the system, we investigate the behaviour of
      the model via numerical simulation and bifurcation analysis. In particular, we
      study the effect of an increase in population size as well as the spatio-temporal
      behaviour of the model. Our results demonstrate that oscillations are possible
      only in the presence of a high concentration of the coupling chemical and are due
      to a time scale separation in key regulatory components of the system. The model
      suggests that the population establishes oscillatory behaviour as the system's
      preferred stable state. This is achieved via an effective increase in coupling
      across the population. We conclude that population effects in GRN design need to
      be taken into consideration and be part of the design process. This is important
      in planning intervention strategies or designing specific cell behaviours.

PMID- 23135247
TI  - Probing articular cartilage damage and disease by quantitative magnetic resonance
      imaging.
AB  - Osteoarthritis (OA) is a debilitating disease that reflects a complex interplay
      of biochemical, biomechanical, metabolic and genetic factors, which are often
      triggered by injury, and mediated by inflammation, catabolic cytokines and
      enzymes. An unmet clinical need is the lack of reliable methods that are able to
      probe the pathogenesis of early OA when disease-rectifying therapies may be most
      effective. Non-invasive quantitative magnetic resonance imaging (qMRI) techniques
      have shown potential for characterizing the structural, biochemical and
      mechanical changes that occur with cartilage degeneration. In this paper, we
      review the background in articular cartilage and OA as it pertains to
      conventional MRI and qMRI techniques. We then discuss how conventional MRI and
      qMRI techniques are used in clinical and research environments to evaluate
      biochemical and mechanical changes associated with degeneration. Some qMRI
      techniques allow for the use of relaxometry values as indirect biomarkers for
      cartilage components. Direct characterization of mechanical behaviour of
      cartilage is possible via other specialized qMRI techniques. The combination of
      these qMRI techniques has the potential to fully characterize the biochemical and
      biomechanical states that represent the initial changes associated with cartilage
      degeneration. Additionally, knowledge of in vivo cartilage biochemistry and
      mechanical behaviour in healthy subjects and across a spectrum of osteoarthritic
      patients could lead to improvements in the detection, management and treatment of
      OA.

PMID- 23135249
TI  - Evolutionary inference for function-valued traits: Gaussian process regression on
      phylogenies.
AB  - Biological data objects often have both of the following features: (i) they are
      functions rather than single numbers or vectors, and (ii) they are correlated
      owing to phylogenetic relationships. In this paper, we give a flexible
      statistical model for such data, by combining assumptions from phylogenetics with
      Gaussian processes. We describe its use as a non-parametric Bayesian prior
      distribution, both for prediction (placing posterior distributions on ancestral
      functions) and model selection (comparing rates of evolution across a phylogeny,
      or identifying the most likely phylogenies consistent with the observed data).
      Our work is integrative, extending the popular phylogenetic Brownian motion and
      Ornstein-Uhlenbeck models to functional data and Bayesian inference, and
      extending Gaussian process regression to phylogenies. We provide a brief
      illustration of the application of our method.

PMID- 23135250
TI  - Introducing a mixed-valent dirhodium(II,III) catalyst with increased stability in
      C-H amination.
AB  - A new mixed-valent Rh(2)(II,III) dimer, [Rh(2)(espn)(2)Cl] (espn(2-) =
      alpha,alpha,alpha',alpha'-tetramethyl-1,3-benzenedipropanamidate), is reported.
      This compound readily dissociates Cl(-) at low concentrations in solution to form
      the active [Rh(2)(espn)(2)](+) catalyst, which performs intramolecular C-H
      amination with TONs > 1400. This work expands the scope of Rh(2)(II,III) dimers
      to nitrenoid chemistry.

PMID- 23135252
TI  - [Comment about the article "Psychopharmaceuticals and diabetes" of Ress C,
      Tschoner A, Kaser S, and Ebenbichler CF in Wiener Medizinische Wochenschrift
      2011; 161/21-22: 531-42].

PMID- 23135251
TI  - Diagnosis of anaemia: old things rearranged.
AB  - Anaemia is one of the most leading causes of morbidity and mortality, as declared
      by the World Health Organisation. This syndrome is characterised by low
      haemoglobin levels and nonspecific clinical symptoms such as weakness, fatigue
      and dyspnoea. The symptoms are unspecific as the underlying causes are
      heterogeneous. Thus, good knowledge of the useful biomarkers and their correct
      assignment is needed to allow rapid and targeted diagnosis.

PMID- 23135254
TI  - A novel recombinant immunocasp-6 fusion gene specifically and efficiently
      suppresses HER2-overexpressing osteosarcoma.
AB  - Osteosarcoma is the most common primary malignant tumor of bone for adolescent or
      children. The poor prognosis of patients, due to its remote metastasis, has led
      to the exploration of more effective and less toxic treatments. Immunotherapy is
      a promising strategy for the treatment of human epidermal growth factor receptor
      2 (HER2)-overexpressing tumors. Herein, we describe experiments conducted with a
      fusion gene, immunocasp-6, which was generated by fusing a HER2-specific single
      chain Ab, a single-chain Pseudomonas exotoxin A and an active caspase-6 which can
      directly cleave lamin A leading to nucleus damage inducing programmed cell death.
      We demonstrated that immunocasp-6 can specifically and efficiently recognize and
      induce apoptosis in HER2-overexpressing osteosarcoma cells in vitro. The
      immunocasp-6 was transferred into BALB/c athymic mice bearing human osteosarcoma
      by i.m. injection of liposome-encapsulated pCMV-immunocap-6. Expression of
      immunocasp-6 not only strongly inhibited tumor growth and significantly prolonged
      animal survival, but also greatly prevented tumor metastasis. Our data showed
      that the immuno-casp-6 can specifically recognize HER2-overexpressing
      osteosarcoma cells, can also promptly attack their nucleus and induce apoptotic
      death, suggesting the potential of this strategy for the treatment of human HER2
      overexpressing tumors.

PMID- 23135255
TI  - Highly ordered pyrene pi-stacks on an RNA duplex display static excimer
      fluorescence.
AB  - The binding and fluorescence properties of complementary RNA sequences attached
      to different numbers of pyrenes via one carbon linker at the 2'-O-positions have
      been investigated. Upon hybridization of the pyrene-modified RNA sequences, the
      modified RNA duplexes with normal thermal stability are formed, and the pyrene
      arrays are assembled in an inter-strand manner. Because hypochromic effects in
      the pyrene absorption band and the exciton coupled circular dichroism signals
      were observed for the pyrene assemblies, the formation of the pyrene array occurs
      via a pi-stacking interaction between the pyrene rings. The pyrene assemblies
      exhibit strong excimer fluorescence that is characterized by a broad and
      structureless excitation spectrum. Hence, the excimer is a static excimer due to
      the direct excitation of the associated pyrenes in the ground state. Based on
      several spectroscopies, it is revealed that the spatial configuration of the
      pyrenes in the association is more regulated by the increase in the attached
      pyrene.

PMID- 23135257
TI  - Diffusion tensor imaging to predict long-term outcome after cardiac arrest: a
      bicentric pilot study.
AB  - BACKGROUND: Prognostication in comatose survivors of cardiac arrest is a major
      clinical challenge. The authors' objective was to determine whether an assessment
      with diffusion tensor imaging, a brain magnetic resonance imaging sequence,
      increases the accuracy of 1 yr functional outcome prediction in cardiac arrest
      survivors. METHODS: Prospective, observational study in two intensive care units.
      Fifty-seven comatose survivors of cardiac arrest underwent brain magnetic
      resonance imaging. Fractional anisotropy (FA), a diffusion tensor imaging value,
      was measured in predefined white matter regions, and apparent diffusion
      coefficient was assessed in predefined grey matter regions. Prediction of
      unfavorable outcome at 1 yr was compared using four prognostic models: FA global,
      FA selected, apparent diffusion coefficient, and clinical classifiers. RESULTS:
      Of the 57 patients included in the study, 49 had an unfavorable outcome at 12
      months. Areas under the receiver operating characteristic curve (95% CI) to
      predict unfavorable outcome for the FA global, FA selected, clinical, and
      apparent diffusion coefficient models were 0.92 (0.82-0.98), 0.96 (0.87-0.99),
      0.78 (0.65-0.88), and 0.86 (0.74-0.94), respectively. The FA selected model had
      the best overall accuracy for predicting outcome, with a score above 0.44 having
      94% (95% CI, 83-99%) sensitivity and 100% (95% CI, 63-100%) specificity for the
      prediction of unfavorable outcome. CONCLUSION: Quantitative diffusion tensor
      imaging indicates that white matter damage is widespread after cardiac arrest. A
      prognostic model based on FA values in selected white matter tracts seems to
      predict accurately 1 yr functional outcome. These preliminary results need to be
      confirmed in a larger population.

PMID- 23135256
TI  - Trauma and conditional risk of posttraumatic stress disorder in two American
      Indian reservation communities.
AB  - PURPOSE: To determine conditional risk of posttraumatic stress disorder (PTSD) in
      two culturally distinct American Indian reservation communities. METHOD: Data
      derived from the American Indian Service Utilization, Psychiatric Epidemiology,
      Risk and Protective Factors Project, a cross-sectional population-based survey
      that was completed between 1997 and 2000. This study focused on 1,967
      participants meeting the DSM-IV criteria for trauma exposure. Traumas were
      grouped into interpersonal, non-interpersonal, witnessed, and "trauma to close
      others" categories. Analyses examined distribution of worst traumas, conditional
      rates of PTSD following exposure, and distributions of PTSD cases deriving from
      these events. Bivariate and multivariate logistic regressions estimated
      associations of lifetime PTSD with trauma type. RESULTS: Overall, 15.9 % of those
      exposed to DSM-IV trauma qualified for lifetime PTSD, a rate comparable to
      similar US studies. Women were more likely to develop PTSD than were men. The
      majority (60 %) of cases of PTSD among women derived from interpersonal trauma
      exposure (in particular, sexual and physical abuse); among men, cases were more
      evenly distributed across trauma categories. CONCLUSIONS: Previous research has
      demonstrated higher rates of both trauma exposure and PTSD in American Indian
      samples compared to other Americans. This study shows that conditional rates of
      PTSD are similar to those reported elsewhere, suggesting that the elevated
      prevalence of this disorder in American Indian populations is largely due to
      higher rates of trauma exposure.

PMID- 23135258
TI  - Interaction of metabolic and respiratory acidosis with alpha and beta
      adrenoceptor stimulation in rat myocardium.
AB  - BACKGROUND: The effects of acute respiratory versus metabolic acidosis on the
      myocardium and their consequences on adrenoceptor stimulation remain poorly
      described. We compared the effects of metabolic and respiratory acidosis on
      inotropy and lusitropy in rat myocardium and their effects on the responses to
      alpha- and beta-adrenoceptor stimulations. METHODS: The effects of acute
      respiratory and metabolic acidosis (pH 7.10) and their interactions with alpha
      and beta-adrenoceptor stimulations were studied in isolated rat left ventricular
      papillary muscle (n=8 per group). Intracellular pH was measured using confocal
      microscopy and a pH-sensitive fluorophore in isolated rat cardiomyocytes. Data
      are mean percentages of baseline+/-SD. RESULTS: Respiratory acidosis induced more
      pronounced negative inotropic effects than metabolic acidosis did both in
      isotonic (45+/-3 versus 63+/-6%, P<0.001) and isometric (44+/-5 versus 64+/-3%,
      P<0.001) conditions concomitant with a greater decrease in intracellular pH
      (6.85+/-0.07 versus 7.12+/-0.07, P<0.001). The response to alpha-adrenergic
      stimulation was not modified by respiratory or metabolic acidosis. The inotropic
      response to beta-adrenergic stimulation was impaired only in metabolic acidosis
      (137+/-12 versus 200+/-33%, P<0.001), but this effect was not observed with
      administration of forskolin or dibutiryl-cyclic adenosine monophosphate. This
      effect might be explained by a change in transmembrane pH gradient only observed
      with metabolic acidosis. The lusitropic response to beta-adrenergic stimulation
      was not modified by respiratory or metabolic acidosis. CONCLUSION: Acute
      metabolic and respiratory acidosis induce different myocardial effects related to
      different decreases in intracellular pH. Only metabolic acidosis impairs the
      positive inotropic effect of beta-adrenergic stimulation.

PMID- 23135259
TI  - Prediction of difficult tracheal intubation: time for a paradigm change.
AB  - BACKGROUND: It has been suggested that predicting difficult tracheal intubation
      is useless because of the poor predictive capacity of individual signs and
      scores. The authors tested the hypothesis that an accurate prediction of
      difficult tracheal intubation using simple clinical signs is possible using a
      computer-assist model. METHODS: In a cohort of 1,655 patients, the authors
      analyzed the predictive properties of each of the main signs (Mallampati score,
      mouth opening, thyromental distance, and body mass index) to predict difficult
      tracheal intubation. They built the best score possible using a simple logistic
      model (SCOREClinic) and compared it with the more recently described score in the
      literature (SCORENaguib). Then they used a boosted tree analysis to build the
      best score possible using computer-assisted calculation (SCOREComputer). RESULTS:
      Difficult tracheal intubation occurred in 101 patients (6.1%). The predictive
      properties of each sign remain low (maximum area under the receiver operating
      characteristic curve 0.70). Using receiver operating characteristic curve, the
      global prediction of the SCOREClinic (0.74, 95% CI: 0.72-0.76) was greater than
      that of the SCORENaguib (0.66, 95% CI: 0.60-0.72, P<0.001) but significantly
      lower than that of the SCOREComputer (0.86, 95% CI: 0.84-0.91, P<0.001). The
      proportion of patients in the inconclusive zone was 71% using SCORENaguib, 56%
      using SCOREClinic, and only 32 % using SCOREComputer (all P<0.001). CONCLUSION:
      Computer-assisted models using complex interaction between variables enable an
      accurate prediction of difficult tracheal intubation with a low proportion of
      patients in the inconclusive zone. An external validation of the model is now
      required.

PMID- 23135260
TI  - Effects of positive end-expiratory pressure titration and recruitment maneuver on
      lung inflammation and hyperinflation in experimental acid aspiration-induced lung
      injury.
AB  - BACKGROUND: In acute lung injury positive end-expiratory pressure (PEEP) and
      recruitment maneuver are proposed to optimize arterial oxygenation. The aim of
      the study was to evaluate the impact of such a strategy on lung histological
      inflammation and hyperinflation in pigs with acid aspiration-induced lung injury.
      METHODS: Forty-seven pigs were randomly allocated in seven groups: (1) controls
      spontaneously breathing; (2) without lung injury, PEEP 5 cm H2O; (3) without lung
      injury, PEEP titration; (4) without lung injury, PEEP titration + recruitment
      maneuver; (5) with lung injury, PEEP 5 cm H2O; (6) with lung injury, PEEP
      titration; and (7) with lung injury, PEEP titration + recruitment maneuver. Acute
      lung injury was induced by intratracheal instillation of hydrochloric acid. PEEP
      titration was performed by incremental and decremental PEEP from 5 to 20 cm H2O
      for optimizing arterial oxygenation. Three recruitment maneuvers (pressure of 40
      cm H2O maintained for 20 s) were applied to the assigned groups at each PEEP
      level. Proportion of lung inflammation, hemorrhage, edema, and alveolar wall
      disruption were recorded on each histological field. Mean alveolar area was
      measured in the aerated lung regions. RESULTS: Acid aspiration increased mean
      alveolar area and produced alveolar wall disruption, lung edema, alveolar
      hemorrhage, and lung inflammation. PEEP titration significantly improved arterial
      oxygenation but simultaneously increased lung inflammation in juxta-diaphragmatic
      lung regions. Recruitment maneuver during PEEP titration did not induce
      additional increase in lung inflammation and alveolar hyperinflation. CONCLUSION:
      In a porcine model of acid aspiration-induced lung injury, PEEP titration aimed
      at optimizing arterial oxygenation, substantially increased lung inflammation.
      Recruitment maneuvers further improved arterial oxygenation without additional
      effects on inflammation and hyperinflation.

PMID- 23135261
TI  - Assessment of white matter injury and outcome in severe brain trauma: a
      prospective multicenter cohort.
AB  - BACKGROUND: Existing methods to predict recovery after severe traumatic brain
      injury lack accuracy. The aim of this study is to determine the prognostic value
      of quantitative diffusion tensor imaging (DTI). METHODS: In a multicenter study,
      the authors prospectively enrolled 105 patients who remained comatose at least 7
      days after traumatic brain injury. Patients underwent brain magnetic resonance
      imaging, including DTI in 20 preselected white matter tracts. Patients were
      evaluated at 1 yr with a modified Glasgow Outcome Scale. A composite DTI score
      was constructed for outcome prognostication on this training database and then
      validated on an independent database (n=38). DTI score was compared with the
      International Mission for Prognosis and Analysis of Clinical Trials Score.
      RESULTS: Using the DTI score for prediction of unfavorable outcome on the
      training database, the area under the receiver operating characteristic curve was
      0.84 (95% CI: 0.75-0.91). The DTI score had a sensitivity of 64% and a
      specificity of 95% for the prediction of unfavorable outcome. On the validation
      independent database, the area under the receiver operating characteristic curve
      was 0.80 (95% CI: 0.54-0.94). On the training database, reclassification methods
      showed significant improvement of classification accuracy (P < 0.05) compared
      with the International Mission for Prognosis and Analysis of Clinical Trials
      score. Similar results were observed on the validation database. CONCLUSIONS:
      White matter assessment with quantitative DTI increases the accuracy of long-term
      outcome prediction compared with the available clinical/radiographic prognostic
      score.

PMID- 23135262
TI  - Can changes in arterial pressure be used to detect changes in cardiac output
      during volume expansion in the perioperative period?
AB  - BACKGROUND: Cardiac output (CO) is rarely monitored during surgery, and arterial
      pressure remains the only hemodynamic parameter for assessing the effects of
      volume expansion (VE). However, whether VE-induced changes in arterial pressure
      accurately reflect changes in CO has not been demonstrated. The authors studied
      the ability of VE-induced changes in arterial pressure and in pulse pressure
      variation to detect changes in CO induced by VE in the perioperative period.
      METHODS: The authors studied 402 patients in four centers. Hemodynamic variables
      were recorded before and after VE. Response to VE was defined as more than 15%
      increase in CO. The ability of VE-induced changes in arterial pressure to detect
      changes in CO was assessed using a gray zone approach. RESULTS: VE increased CO
      of more than 15% in 205 patients (51%). Areas under the receiver operating
      characteristic curves for VE-induced changes in systolic, diastolic, means, and
      pulse pressure ranged between 0.64 and 0.70, and sensitivity and specificity
      ranged between 52 and 79%. For these four arterial pressure-derived parameters,
      large gray zones were found, and more than 60% of the patients lay within this
      inconclusive zone. A VE-induced decrease in pulse pressure variation of 3% or
      more allowed detecting a fluid-induced increase in CO of more than 15% with a
      sensitivity of 90% and a specificity of 77% and a gray zone between 2.2 and 4.7%
      decrease in pulse pressure variation including 14% of the patients. CONCLUSION:
      Only changes in pulse pressure variation accurately detect VE-induced changes in
      CO and have a potential clinical applicability.

PMID- 23135263
TI  - Contribution of the Pitie-Salpetriere Hospital to French anesthesiology.

PMID- 23135264
TI  - Aerosolized antibiotics for ventilator-associated pneumonia: lessons from
      experimental studies.
AB  - The aim of this review is to perform a critical analysis of experimental studies
      on aerosolized antibiotics and draw lessons for clinical use in patients with
      ventilator-associated pneumonia. Ultrasonic or vibrating plate nebulizers should
      be preferred to jet nebulizers. During the nebulization period, specific
      ventilator settings aimed at decreasing flow turbulence should be used, and
      discoordination with the ventilator should be avoided. The appropriate dose of
      aerosolized antibiotic can be determined as the intravenous dose plus
      extrapulmonary deposition. If these conditions are strictly respected, then high
      lung tissue deposition associated with rapid and efficient bacterial killing can
      be expected. For aerosolized aminoglycosides and cephalosporins, a decrease in
      systemic exposure leading to reduced toxicity is not proven by experimental
      studies. Aerosolized colistin, however, does not easily cross the alveolar
      capillary membrane even in the presence of severe lung infection, and high doses
      can be delivered by nebulization without significant systemic exposure.

PMID- 23135265
TI  - The intermediate filament vimentin mediates microRNA miR-378 function in cellular
      self-renewal by regulating the expression of the Sox2 transcription factor.
AB  - MicroRNAs are short noncoding RNAs that are implicated in cell self- renewal and
      cancer development. We show that miR-378 is up-regulated in human cancers and
      found that tumor cells transfected with miR-378 acquired properties of tumor stem
      cells, including cell self-renewal. Overexpression of miR-378 enhanced cell
      survival and colony formation. Isolated from a single-cell colony, the miR-378
      expressing cells formed tumors in nude mice at low cell densities. These cells
      expressed higher levels of miR-378 and formed more and larger spheres and
      colonies. We found that the miR-378-expressing cells contained a large number of
      side population cells and could undergo differentiation. Cells transfected with
      miR-378 expressed increased levels of Sox2. Expression of miR-378 and Sox2 was
      found correlated significantly in cancer cell lines and in cancer patient
      specimens. We also observed opposite levels of vimentin in the cancer cell lines
      and human breast carcinoma specimens. We further demonstrated that vimentin is a
      target of miR-378, and ectopic transfection of vimentin inhibited Sox2
      expression, resulting in decreased cell survival. Silencing vimentin promoted
      Sox2 expression and cell survival. Our study demonstrates that miR-378 is a
      regulator of stem cell marker Sox2 by targeting vimentin, which may serve as a
      new tool in studying the role of stem cells in tumorigenesis.

PMID- 23135266
TI  - Evaluating Drosophila p53 as a model system for studying cancer mutations.
AB  - The transcription factor p53 is a key tumor suppressor protein. In about half of
      human cancers, p53 is inactivated directly through mutation in its sequence
      specific DNA-binding domain. Drosophila p53 (Dmp53) has similar apoptotic
      functions as its human homolog and is therefore an attractive model system for
      studying cancer pathways. To probe the structure and function of Dmp53, we
      studied the effect of point mutations, corresponding to cancer hot spot mutations
      in human p53 (Hp53), on the stability and DNA binding affinity of the full-length
      protein. Despite low sequence conservation, the Hp53 and Dmp53 proteins had a
      similar melting temperature and generally showed a similar energetic and
      functional response to cancer-associated mutations. We also found a correlation
      between the thermodynamic stability of the mutant proteins and their rate of
      aggregation. The effects of the mutations were rationalized based on homology
      modeling of the Dmp53 DNA-binding domain, suggesting that the drastically
      different effects of a cancer mutation in the loop-sheet-helix motif (R282W in
      Hp53 and R268W in Dmp53) on stability and DNA binding affinity of the two
      proteins are related to conformational differences in the L1 loop adjacent to the
      mutation site. On the basis of these data, we discuss the advantages and
      limitations of using Dmp53 as a model system for studying p53 function and
      testing p53 rescue drugs.

PMID- 23135267
TI  - Mitoferrin-2-dependent mitochondrial iron uptake sensitizes human head and neck
      squamous carcinoma cells to photodynamic therapy.
AB  - Photodynamic therapy (PDT) is a promising approach to treat head and neck cancer
      cells. Here, we investigated whether mitochondrial iron uptake through mitoferrin
      2 (Mfrn2) enhanced PDT-induced cell killing. Three human head and neck squamous
      carcinoma cell lines (UMSCC1, UMSCC14A, and UMSCC22A) were exposed to light and
      Pc 4, a mitochondria-targeted photosensitizer. The three cell lines responded
      differently: UMSCC1 and UMSCC14A cells were more resistant, whereas UMSCC22A
      cells were more sensitive to Pc 4-PDT-induced cell death. In non-erythroid cells,
      Mfrn2 is an iron transporter in the mitochondrial inner membrane. PDT-sensitive
      cells expressed higher Mfrn2 mRNA and protein levels compared with PDT-resistant
      cells. High Mfrn2-expressing cells showed higher rates of mitochondrial Fe(2+)
      uptake compared with low Mfrn2-expressing cells. Bafilomycin, an inhibitor of the
      vacuolar proton pump of lysosomes and endosomes that causes lysosomal iron
      release to the cytosol, enhanced PDT-induced cell killing of both resistant and
      sensitive cells. Iron chelators and the inhibitor of the mitochondrial Ca(2+)
      (and Fe(2+)) uniporter, Ru360, protected against PDT plus bafilomycin toxicity.
      Knockdown of Mfrn2 in UMSCC22A cells decreased the rate of mitochondrial Fe(2+)
      uptake and delayed PDT plus bafilomycin-induced mitochondrial depolarization and
      cell killing. Taken together, the data suggest that lysosomal iron release and
      Mfrn2-dependent mitochondrial iron uptake act synergistically to induce PDT
      mediated and iron-dependent mitochondrial dysfunction and subsequent cell
      killing. Furthermore, Mfrn2 represents a possible biomarker of sensitivity of
      head and neck cancers to cell killing after PDT.

PMID- 23135268
TI  - G protein-coupled estrogen receptor mediates the up-regulation of fatty acid
      synthase induced by 17beta-estradiol in cancer cells and cancer-associated
      fibroblasts.
AB  - Activation of lipid metabolism is an early event in carcinogenesis and a central
      hallmark of many tumors. Fatty acid synthase (FASN) is a key lipogenic enzyme
      catalyzing the terminal steps in the de novo biogenesis of fatty acids. In cancer
      cells, FASN may act as a metabolic oncogene, given that it confers growth and
      survival advantages to these cells, whereas its inhibition effectively and
      selectively kills tumor cells. Hormones such as estrogens and growth factors
      contribute to the transcriptional regulation of FASN expression also through the
      activation of downstream signaling and a cross-talk among diverse transduction
      pathways. In this study, we demonstrate for the first time that 17beta-estradiol
      (E2) and the selective GPER ligand G-1 regulate FASN expression and activity
      through the GPER-mediated signaling, which involved the EGF receptor/ERK/c
      Fos/AP1 transduction pathway, as ascertained by using specific pharmacological
      inhibitors, performing gene-silencing experiments and ChIP assays in breast
      SkBr3, colorectal LoVo, hepatocarcinoma HepG2 cancer cells, and breast cancer
      associated fibroblasts. In addition, the proliferative effects induced by E2 and
      G-1 in these cells involved FASN as the inhibitor of its activity, named
      cerulenin, abolished the growth response to both ligands. Our data suggest that
      GPER may be included among the transduction mediators involved by estrogens in
      regulating FASN expression and activity in cancer cells and cancer-associated
      fibroblasts that strongly contribute to cancer progression.

PMID- 23135269
TI  - Sphingosine 1-phosphate (S1P) carrier-dependent regulation of endothelial
      barrier: high density lipoprotein (HDL)-S1P prolongs endothelial barrier
      enhancement as compared with albumin-S1P via effects on levels, trafficking, and
      signaling of S1P1.
AB  - Sphingosine 1-phosphate (S1P) is a blood-borne lysosphingolipid that acts to
      promote endothelial cell (EC) barrier function. In plasma, S1P is associated with
      both high density lipoproteins (HDL) and albumin, but it is not known whether the
      carriers impart different effects on S1P signaling. Here we establish that HDL
      S1P sustains EC barrier longer than albumin-S1P. We showed that the sustained
      barrier effects of HDL-S1P are dependent on signaling by the S1P receptor, S1P1,
      and involve persistent activation of Akt and endothelial NOS (eNOS), as well as
      activity of the downstream NO target, soluble guanylate cyclase (sGC). Total S1P1
      protein levels were found to be higher in response to HDL-S1P treatment as
      compared with albumin-S1P, and this effect was not associated with increased S1P1
      mRNA or dependent on de novo protein synthesis. Several pieces of evidence
      indicate that long term EC barrier enhancement activity of HDL-S1P is due to
      specific effects on S1P1 trafficking. First, the rate of S1P1 degradation, which
      is proteasome-mediated, was slower in HDL-S1P-treated cells as compared with
      cells treated with albumin-S1P. Second, the long term barrier-promoting effects
      of HDL-S1P were abrogated by treatment with the recycling blocker, monensin.
      Finally, cell surface levels of S1P1 and levels of S1P1 in caveolin-enriched
      microdomains were higher after treatment with HDL-S1P as compared with albumin
      S1P. Together, the findings reveal S1P carrier-specific effects on S1P1 and point
      to HDL as the physiological mediator of sustained S1P1-PI3K-Akt-eNOS-sGC
      dependent EC barrier function.

PMID- 23135270
TI  - Furin-cleaved proprotein convertase subtilisin/kexin type 9 (PCSK9) is active and
      modulates low density lipoprotein receptor and serum cholesterol levels.
AB  - Proprotein convertase subtilisin/kexin 9 (PCSK9) regulates plasma LDL cholesterol
      levels by regulating the degradation of LDL receptors. Another proprotein
      convertase, furin, cleaves PCSK9 at Arg(218)-Gln(219) in the surface-exposed "218
      loop." This cleaved form circulates in blood along with the intact form, albeit
      at lower concentrations. To gain a better understanding of how cleavage affects
      PCSK9 function, we produced recombinant furin-cleaved PCSK9 using antibody Ab
      3D5, which binds the intact but not the cleaved 218 loop. Using Ab-3D5, we also
      produced highly purified hepsin-cleaved PCSK9. Hepsin cleaves PCSK9 at Arg(218)
      Gln(219) more efficiently than furin but also cleaves at Arg(215)-Phe(216).
      Further analysis by size exclusion chromatography and mass spectrometry indicated
      that furin and hepsin produced an internal cleavage in the 218 loop without the
      loss of the N-terminal segment (Ser(153)-Arg(218)), which remained attached to
      the catalytic domain. Both furin- and hepsin-cleaved PCSK9 bound to LDL receptor
      with only 2-fold reduced affinity compared with intact PCSK9. Moreover, they
      reduced LDL receptor levels in HepG2 cells and in mouse liver with only
      moderately lower activity than intact PCSK9, consistent with the binding data.
      Single injection into mice of furin-cleaved PCSK9 resulted in significantly
      increased serum cholesterol levels, approaching the increase by intact PCSK9.
      These findings indicate that circulating furin-cleaved PCSK9 is able to regulate
      LDL receptor and serum cholesterol levels, although somewhat less efficiently
      than intact PCSK9. Therapeutic anti-PCSK9 approaches that neutralize both forms
      should be the most effective in preserving LDL receptors and in lowering plasma
      LDL cholesterol.

PMID- 23135271
TI  - PheVI:09 (Phe6.44) as a sliding microswitch in seven-transmembrane (7TM) G
      protein-coupled receptor activation.
AB  - In seven-transmembrane (7TM), G protein-coupled receptors, highly conserved
      residues function as microswitches, which alternate between different
      conformations and interaction partners in an extended allosteric interface
      between the transmembrane segments performing the large scale conformational
      changes upon receptor activation. Computational analysis using x-ray structures
      of the beta(2)-adrenergic receptor demonstrated that PheVI:09 (6.44), which in
      the inactive state is locked between the backbone and two hydrophobic residues in
      transmembrane (TM)-III, upon activation slides ~2 A toward TM-V into a tight
      pocket generated by five hydrophobic residues protruding from TM-III and TM-V. Of
      these, the residue in position III:16 (3.40) (often an Ile or Val) appears to
      function as a barrier or gate for the transition between inactive and active
      conformation. Mutational analysis showed that PheVI:09 is essential for the
      constitutive and/or agonist-induced signaling of the ghrelin receptor, GPR119,
      the beta(2)-adrenergic receptor, and the neurokinin-1 receptor. Substitution of
      the residues constituting the hydrophobic pocket between TM-III and TM-V in the
      ghrelin receptor in four of five positions impaired receptor signaling. In GPR39,
      representing the 12% of 7TM receptors lacking an aromatic residue at position
      VI:09, unchanged agonist-induced signaling was observed upon Ala substitution of
      LeuVI:09 despite reduced cell surface expression of the mutant receptor. It is
      concluded that PheVI:09 constitutes an aromatic microswitch that stabilizes the
      active, outward tilted conformation of TM-VI relative to TM-III by sliding into a
      tight hydrophobic pocket between TM-III and TM-V and that the hydrophobic residue
      in position III:16 constitutes a gate for this transition.

PMID- 23135272
TI  - Conservation of flexible residue clusters among structural and functional enzyme
      homologues.
AB  - Conformational flexibility between structural ensembles is an essential component
      of enzyme function. Although the broad dynamical landscape of proteins is known
      to promote a number of functional events on multiple time scales, it is yet
      unknown whether structural and functional enzyme homologues rely on the same
      concerted residue motions to perform their catalytic function. It is hypothesized
      that networks of contiguous and flexible residue motions occurring on the
      biologically relevant millisecond time scale evolved to promote and/or preserve
      optimal enzyme catalysis. In this study, we use a combination of NMR relaxation
      dispersion, model-free analysis, and ligand titration experiments to successfully
      capture and compare the role of conformational flexibility between two structural
      homologues of the pancreatic ribonuclease family: RNase A and eosinophil cationic
      protein (or RNase 3). In addition to conserving the same catalytic residues and
      structural fold, both homologues show similar yet functionally distinct clusters
      of millisecond dynamics, suggesting that conformational flexibility can be
      conserved among analogous protein folds displaying low sequence identity. Our
      work shows that the reduced conformational flexibility of eosinophil cationic
      protein can be dynamically and functionally reproduced in the RNase A scaffold
      upon creation of a chimeric hybrid between the two proteins. These results
      support the hypothesis that conformational flexibility is partly required for
      catalytic function in homologous enzyme folds, further highlighting the
      importance of dynamic residue sectors in the structural organization of proteins.

PMID- 23135273
TI  - The structural basis of force generation by the mitotic motor kinesin-5.
AB  - Kinesin-5 is required for forming the bipolar spindle during mitosis. Its motor
      domain, which contains nucleotide and microtubule binding sites and mechanical
      elements to generate force, has evolved distinct properties for its spindle-based
      functions. In this study, we report subnanometer resolution cryoelectron
      microscopy reconstructions of microtubule-bound human kinesin-5 before and after
      nucleotide binding and combine this information with studies of the kinetics of
      nucleotide-induced neck linker and cover strand movement. These studies reveal
      coupled, nucleotide-dependent conformational changes that explain many of this
      motor's properties. We find that ATP binding induces a ratchet-like docking of
      the neck linker and simultaneous, parallel docking of the N-terminal cover
      strand. Loop L5, the binding site for allosteric inhibitors of kinesin-5, also
      undergoes a dramatic reorientation when ATP binds, suggesting that it is directly
      involved in controlling nucleotide binding. Our structures indicate that
      allosteric inhibitors of human kinesin-5, which are being developed as anti
      cancer therapeutics, bind to a motor conformation that occurs in the course of
      normal function. However, due to evolutionarily defined sequence variations in
      L5, this conformation is not adopted by invertebrate kinesin-5s, explaining their
      resistance to drug inhibition. Together, our data reveal the precision with which
      the molecular mechanism of kinesin-5 motors has evolved for force generation.

PMID- 23135274
TI  - Role of the actin Ala-108-Pro-112 loop in actin polymerization and ATPase
      activities.
AB  - Actin plays fundamental roles in a variety of cell functions in eukaryotic cells.
      The polymerization-depolymerization cycle, between monomeric G-actin and fibrous
      F-actin, drives essential cell processes. Recently, we proposed the atomic model
      for the F-actin structure and found that actin was in the twisted form in the
      monomer and in the untwisted form in the filament. To understand how the
      polymerization process is regulated (Caspar, D. L. (1991) Curr. Biol. 1, 30-32),
      we need to know further details about the transition from the twisted to the
      untwisted form. For this purpose, we focused our attention on the Ala-108-Pro-112
      loop, which must play crucial roles in the transition, and analyzed the
      consequences of the amino acid replacements on the polymerization process. As
      compared with the wild type, the polymerization of P109A was accelerated in both
      the nucleation and the elongation steps, and this was attributed to an increase
      in the frequency factor of the Arrhenius equation. The multiple conformations
      allowed by the substitution presumably resulted in the effective formation of the
      collision complex, thus accelerating polymerization. On the other hand, the A108G
      mutation reduced the rates of both nucleation and elongation due to an increase
      in the activation energy. In the cases of polymerization acceleration and
      deceleration, each functional aberration is attributed to a distinct elementary
      process. The rigidity of the loop, which mediates neither too strong nor too weak
      interactions between subdomains 1 and 3, might play crucial roles in actin
      polymerization.

PMID- 23135275
TI  - Selective proteasomal degradation of the B'beta subunit of protein phosphatase 2A
      by the E3 ubiquitin ligase adaptor Kelch-like 15.
AB  - Protein phosphatase 2A (PP2A), a ubiquitous and pleiotropic regulator of
      intracellular signaling, is composed of a core dimer (AC) bound to a variable (B)
      regulatory subunit. PP2A is an enzyme family of dozens of heterotrimers with
      different subcellular locations and cellular substrates dictated by the B
      subunit. B'beta is a brain-specific PP2A regulatory subunit that mediates
      dephosphorylation of Ca(2+)/calmodulin-dependent protein kinase II and tyrosine
      hydroxylase. Unbiased proteomic screens for B'beta interactors identified Cullin3
      (Cul3), a scaffolding component of E3 ubiquitin ligase complexes, and the
      previously uncharacterized Kelch-like 15 (KLHL15). KLHL15 is one of ~40 Kelch
      like proteins, many of which have been identified as adaptors for the recruitment
      of substrates to Cul3-based E3 ubiquitin ligases. Here, we report that KLHL15
      Cul3 specifically targets B'beta to promote turnover of the PP2A subunit by
      ubiquitylation and proteasomal degradation. Comparison of KLHL15 and B'beta
      tissue expression profiles suggests that the E3 ligase adaptor contributes to
      selective expression of the PP2A/B'beta holoenzyme in the brain. We mapped KLHL15
      residues critical for homodimerization as well as interaction with Cul3 and
      B'beta. Explaining PP2A subunit selectivity, the divergent N terminus of B'beta
      was found necessary and sufficient for KLHL15-mediated degradation, with Tyr-52
      having an obligatory role. Although KLHL15 can interact with the PP2A/B'beta
      heterotrimer, it only degrades B'beta, thus promoting exchange with other
      regulatory subunits. E3 ligase adaptor-mediated control of PP2A holoenzyme
      composition thereby adds another layer of regulation to cellular
      dephosphorylation events.

PMID- 23135276
TI  - Metformin regulates glucose transporter 4 (GLUT4) translocation through AMP
      activated protein kinase (AMPK)-mediated Cbl/CAP signaling in 3T3-L1 preadipocyte
      cells.
AB  - Metformin is a leading oral anti-diabetes mellitus medication and is known to
      stimulate GLUT4 translocation. However, the mechanism by which metformin acts is
      still largely unknown. Here, we showed that short time treatment with metformin
      rapidly increased phosphorylation of Cbl in an AMP-activated protein kinase
      (AMPK)-dependent fashion in 3T3-L1 preadipocytes. Metformin also increased
      phosphorylation of Src in an AMPK-dependent manner. Src inhibition blocked
      metformin-mediated Cbl phosphorylation, suggesting that metformin stimulates AMPK
      Src-Cbl axis pathway. In addition, long term treatment with metformin stimulated
      the expression of Cbl-associated protein (CAP) mRNA and protein. Long term
      treatment with metformin stimulated phosphorylation of c-Jun N-terminal kinase
      (JNK) and its downstream molecule c-Jun, which is a critical molecule for CAP
      transcription. Knockdown of AMPK and JNK blocked metformin-induced expression of
      CAP, implying that metformin stimulates AMPK-JNK-CAP axis pathway. Moreover, AMPK
      knockdown attenuated metformin-induced Cbl/CAP multicomplex formation, which is
      critical for GLUT4 translocation. A colorimetric absorbance assay demonstrated
      that metformin-induced translocation of GLUT4 was suppressed in CAP or Cbl
      knockdown cells. Furthermore, the promoter activity of CAP was increased by
      metformin in an AMPK/JNK-dependent fashion. In summary, these results demonstrate
      that metformin modulates GLUT4 translocation by regulating Cbl and CAP signals
      via AMPK.

PMID- 23135277
TI  - F-box and leucine-rich repeat protein 5 (FBXL5) is required for maintenance of
      cellular and systemic iron homeostasis.
AB  - Maintenance of cellular iron homeostasis requires post-transcriptional regulation
      of iron metabolism genes by iron regulatory protein 2 (IRP2). The hemerythrin
      like domain of F-box and leucine-rich repeat protein 5 (FBXL5), an E3 ubiquitin
      ligase subunit, senses iron and oxygen availability and facilitates IRP2
      degradation in iron replete cells. Disruption of the ubiquitously expressed
      murine Fbxl5 gene results in a failure to sense increased cellular iron
      availability, accompanied by constitutive IRP2 accumulation and misexpression of
      IRP2 target genes. FBXL5-null mice die during embryogenesis, although viability
      is restored by simultaneous deletion of the IRP2, but not IRP1, gene. Mice
      containing a single functional Fbxl5 allele behave like their wild type
      littermates when fed an iron-sufficient diet. However, unlike wild type mice that
      manifest decreased hematocrit and hemoglobin levels when fed a low-iron diet,
      Fbxl5 heterozygotes maintain normal hematologic values due to increased iron
      absorption. The responsiveness of IRP2 to low iron is specifically enhanced in
      the duodena of the heterozygotes and is accompanied by increased expression of
      the divalent metal transporter-1. These results confirm the role of FBXL5 in the
      in vivo maintenance of cellular and systemic iron homeostasis and reveal a
      privileged role for the intestine in their regulation by virtue of its unique
      FBXL5 iron sensitivity.

PMID- 23135278
TI  - The role of microtubules and their dynamics in cell migration.
AB  - Although microtubules have long been implicated in cell locomotion, the mechanism
      of their involvement remains controversial. Most studies have concluded that
      microtubules play a positive role by regulating actin polymerization,
      transporting membrane vesicles to the leading edge, and/or facilitating the
      turnover of adhesion plaques. Here we used wild-type and mutant CHO cell lines
      with alterations in tubulin to demonstrate that microtubules can also act to
      restrain cell motility. Tubulin mutations or low concentrations of drugs that
      suppress microtubule dynamics without affecting the amount of microtubule polymer
      inhibited the rate of migration by preventing microtubule reorganization in the
      trailing portion of the cells where the more dynamic microtubules are normally
      found. Under these conditions, cells along the edge of a wound still extended
      lamellipodia and elongated toward the wound but were inhibited in their ability
      to retract their tails, thus retarding forward progress. The idea that
      microtubules normally act to restrain cell locomotion was confirmed by treating
      cells with high concentrations of nocodazole to depolymerize the microtubule
      network. In the absence of microtubules, wild-type CHO and HeLa cells could still
      move at near normal speeds, but the movement became more random. We conclude that
      microtubules act both to restrain cell movement and to establish directionality.

PMID- 23135279
TI  - Toll-like receptor 11 (TLR11) prevents Salmonella penetration into the murine
      Peyer patches.
AB  - Toll-like receptors (TLRs) are key molecular sensors used by the mammalian innate
      immune system to detect microorganisms. Although TLR functions in colonic immune
      homeostasis and tolerance to commensal bacteria have been intensively researched,
      the precise roles of different TLRs in response to pathogen infection in the gut
      remain elusive. Peyer patches are the major entrance of Salmonella infection and
      antigen transportation in intestine. Here, we report that, in contrast to TLR5 as
      a "carrier of Salmonella," TLR11 works as a "blocker of Salmonella" to prevent
      highly invasive Salmonella from penetrating into the murine Peyer patches and
      spreading systemically. TLR11 plays an important role in mediating TNF-alpha
      induction and systemic inflammation in response to Salmonella infection.
      Remarkably, in mice lacking TLR11, apparent hemorrhages at Peyer patches are
      induced by highly invasive Salmonella, a phenotype resembling human Salmonella
      infection. Therefore, our results indicate a potentially important role for TLR11
      in preventing murine intestinal infection and modulating antigen transportation
      in the gut and imply an important role for various TLRs in cooperation with tight
      control of pathogens penetrating into Peyer patches. The TLR11 knock-out mouse
      can serve as a good animal model to study Salmonella infection.

PMID- 23135280
TI  - Analysis of small molecule ligands targeting the HIV-1 matrix protein-RNA binding
      site.
AB  - The matrix domain (MA) of the HIV-1 precursor Gag (PrGag) protein directs PrGag
      proteins to assembly sites at the plasma membrane by virtue of its affinity to
      the phospholipid, phosphatidylinositol-4,5-bisphosphate (PI(4,5)P(2)). MA also
      binds to RNA at a site that overlaps its PI(4,5)P(2) site, suggesting that RNA
      binding may protect MA from associating with inappropriate cellular membranes
      prior to PrGag delivery to the PM. Based on this, we have developed an assay in
      which small molecule competitors to MA-RNA binding can be characterized, with the
      assumption that such compounds might interfere with essential MA functions and
      help elucidate additional features of MA binding. Following this approach, we
      have identified four compounds, including three thiadiazolanes, that compete with
      RNA for MA binding. We also have identified MA residues involved in thiadiazolane
      binding and found that they overlap the MA PI(4,5)P(2) and RNA sites. Cell
      culture studies demonstrated that thiadiazolanes inhibit HIV-1 replication but
      are associated with significant levels of toxicity. Nevertheless, these
      observations provide new insights into MA binding and pave the way for the
      development of antivirals that target the HIV-1 matrix domain.

PMID- 23135281
TI  - Mediator phosphorylation prevents stress response transcription during non-stress
      conditions.
AB  - The multiprotein complex Mediator is a coactivator of RNA polymerase (Pol) II
      transcription that is required for the regulated expression of protein-coding
      genes. Mediator serves as an end point of signaling pathways and regulates Pol II
      transcription, but the mechanisms it uses are not well understood. Here, we used
      mass spectrometry and dynamic transcriptome analysis to investigate a functional
      role of Mediator phosphorylation in gene expression. Affinity purification and
      mass spectrometry revealed that Mediator from the yeast Saccharomyces cerevisiae
      is phosphorylated at multiple sites of 17 of its 25 subunits. Mediator
      phosphorylation levels change upon an external stimulus set by exposure of cells
      to high salt concentrations. Phosphorylated sites in the Mediator tail subunit
      Med15 are required for suppression of stress-induced changes in gene expression
      under non-stress conditions. Thus dynamic and differential Mediator
      phosphorylation contributes to gene regulation in eukaryotic cells.

PMID- 23135282
TI  - The E3 ubiquitin ligase HOS1 regulates Arabidopsis flowering by mediating
      CONSTANS degradation under cold stress.
AB  - The timing of flowering is coordinated by a web of gene regulatory networks that
      integrates developmental and environmental cues in plants. Light and temperature
      are two major environmental determinants that regulate flowering time. Although
      prolonged treatment with low nonfreezing temperatures accelerates flowering by
      stable repression of FLOWERING LOCUS C (FLC), repeated brief cold treatments
      delay flowering. Here, we report that intermittent cold treatments trigger the
      degradation of CONSTANS (CO), a central activator of photoperiodic flowering;
      daily treatments caused suppression of the floral integrator FLOWERING LOCUS T
      (FT) and delayed flowering. Cold-induced CO degradation is mediated via a
      ubiquitin/proteasome pathway that involves the E3 ubiquitin ligase HIGH
      EXPRESSION OF OSMOTICALLY RESPONSIVE GENE 1 (HOS1). HOS1-mediated CO degradation
      occurs independently of the well established cold response pathways. It is also
      independent of the light signaling repressor CONSTITUTIVE PHOTOMORPHOGENIC 1
      (COP1) E3 ligase and light wavelengths. CO has been shown to play a key role in
      photoperiodic flowering. Here, we demonstrated that CO served as a molecular hub,
      integrating photoperiodic and cold stress signals into the flowering genetic
      pathways. We propose that the HOS1-CO module contributes to the fine-tuning of
      photoperiodic flowering under short term temperature fluctuations, which often
      occur during local weather disturbances.

PMID- 23135283
TI  - PAX2 protein induces expression of cyclin D1 through activating AP-1 protein and
      promotes proliferation of colon cancer cells.
AB  - Paired box (PAX) 2, a transcription factor, plays a critical role in
      embryogenesis. When aberrantly expressed in adult tissues, it generally exhibits
      oncogenic properties. However, the underlying mechanisms remain unclear. We
      reported previously that the expression of PAX2 was up-regulated in human colon
      cancers. However, the role of PAX2 in colon cancer cells has yet to be
      determined. The aim of this study is to determine the function of PAX2 in colon
      cancer cells and to investigate the possible mechanisms underlain. We find that
      knockdown of PAX2 inhibits proliferation and xenograft growth of colon cancer
      cells. Inhibition of PAX2 results in a decreased expression of cyclin D1.
      Expression of cyclin D1 is found increased in human primary colon malignant
      tumors, and its expression is associated with that of PAX2. These data indicate
      that PAX2 is a positive regulator of expression of cyclin D1. We find that
      knockdown of PAX2 inhibits the activity of AP-1, a transcription factor that
      induces cyclin D1 expression, implying that PAX2 induces cyclin D1 through AP-1.
      PAX2 has little effect on expression of AP-1 members including c-Jun, c-Fos, and
      JunB. Our data show that PAX2 prevents JunB from binding c-Jun and enhances
      phosphorylation of c-Jun, which may elevate the activity of AP-1. Taken together,
      these results suggest that PAX2 promotes proliferation of colon cancer cells
      through AP-1.

PMID- 23135284
TI  - A fluorenone based low band gap solution processable copolymer for air stable and
      high mobility organic field effect transistors.
AB  - A fluorenone based alternating copolymer () with a furan based fused aromatic
      moiety has been designed and synthesized.  exhibits a small band gap with a lower
      HOMO value. Testing this polymer semiconductor as the active layer in organic
      thin-film transistors results in hole mobilities as high as 0.15 cm(2) V(-1) s(
      1) in air.

PMID- 23135285
TI  - Assessing small-volume spinal cord dose for repeat spinal stereotactic body
      radiotherapy treatments.
AB  - Spinal cord biologically effective dose (BED) limits are critical to safe spine
      stereotactic body radiotherapy (SBRT) delivery. In particular, when repeating
      SBRT to the same site, the problem of adding non-uniform BED distributions within
      small volumes of spinal cord has yet to be solved. We report a probability-based
      generalized BED (gBED) model to guide repeat spine SBRT treatment planning. The
      gBED was formulated by considering the sequential damaging probabilities of
      repeat spine SBRT treatments. Parameters from the standard linear-quadratic
      model, such as alpha/beta = 2 Gy for the spinal cord, were applied. We tested the
      model based on SBRT specific spinal cord tolerance using a simulated and ten
      clinical repeat SBRT cases. The gBED provides a consistent solution for
      superimposing non-uniform dose distributions from different fractionation
      schemes, analogous to the BED for uniform dose distributions. Based on ten
      clinical cases, the gBED was observed to eliminate discrepancies in the
      cumulative BED of approximately 5% to 20% within small volumes (e.g. 0.1-2.0 cc)
      of spinal cord, as compared to a conventional calculation method. When assessing
      spinal cord tolerance for repeat spinal SBRT treatments, caution should be
      exercised when applying conventional BED calculations for small volumes of spinal
      cord irradiated, and the gBED potentially provides more conservative and
      consistently derived dose surrogates to guide safe treatment planning and
      treatment outcome modeling.

PMID- 23135286
TI  - Can suicide be prevented?

PMID- 23135287
TI  - Direct evidence for active site-dependent formic acid electro-oxidation by
      topmost-surface atomic redistribution in a ternary PtPdCu electrocatalyst.
AB  - The active site-dependent electrochemical formic acid oxidation was evidenced by
      the increased coverage of Pt in the topmost mixed PtPd alloy layer of ternary
      PtPdCu upon potential cycling, which demonstrated two catalytic pathways only in
      one catalyst owing to surface atomic redistribution in an acidic electrolyte
      environment.

PMID- 23135288
TI  - Increased intrasubject variability in boys with ADHD across tests of motor and
      cognitive control.
AB  - Increased intrasubject variability (ISV), or short-term, within-person
      fluctuations in behavioral performance is consistently found in Attention
      Deficit/Hyperactivity Disorder (ADHD). ADHD is also associated with impairments
      in motor control, particularly in boys. The results of the few studies that have
      examined variability in self-generated motor output in children with ADHD have
      been inconsistent. The current study examined variability in motor control during
      a finger sequencing task among boys with and without ADHD as well as the
      relationship between intrasubject variability during motor and cognitive control
      tasks. Changes in performance over the course of the task and associations with
      ADHD symptom domains were also examined to elucidate the nature of impaired motor
      control in children with ADHD. Fifty-one boys (ages 8 to 12 years) participated
      in the study, including 28 boys with ADHD and 23 typically developing (TD) boys.
      Participants completed a finger sequencing task and a Go/No-Go task providing
      multiple measures of response speed and variability. Boys with ADHD were slower
      and more variable in both intertap interval on the finger sequencing task and
      reaction time on the Go/No-Go task, with measures of speed and variability
      correlated across the two tasks. For the entire cohort, the only unique predictor
      of parent ratings of hyperactive-impulsive symptoms was variability in intertap
      interval during finger sequencing, whereas inattentive symptoms were only
      predicted by reaction time variability on the Go/No-Go task. These findings
      suggest that inefficient motor control is implicated in the pathophysiology of
      ADHD, particularly in regards to developmentally inappropriate levels of
      hyperactivity and impulsivity.

PMID- 23135289
TI  - From parent to child to parent...: paths in and out of problem behavior.
AB  - This study used data from the NICHD Study of Early Child Care and Youth
      Development to examine relations between parenting, self-control and
      externalizing behavior from early childhood to mid-adolescence (N = 956; 49.9 %
      male). Results indicated that maternal sensitivity, parental harshness and
      productive activity are related to externalizing problems but that patterns of
      relations change from early childhood to middle childhood to adolescence, with
      evidence suggesting that externalizing behavior influences parenting more than
      the reverse from middle childhood onward. Self-control measured during early
      adolescence partially mediated relations between maternal sensitivity and
      adolescent-reported externalizing behavior. Parental monitoring during
      adolescence was also related to externalizing behavior at age 15. Monitoring
      partially mediated the relation between externalizing behavior in early
      adolescence and externalizing at age 15.

PMID- 23135290
TI  - Thymoquinone blocks pSer/pThr recognition by Plk1 Polo-box domain as a phosphate
      mimic.
AB  - Phosphorylation-dependent protein-protein interaction has rarely been targeted in
      medicinal chemistry. Thymoquinone, a naturally occurring antitumor agent,
      disrupts prephosphorylated substrate recognition by the polo-box domain of polo
      like kinase 1, a key mitotic regulator responsible for various carcinogenesis
      when overexpressed. Here, crystallographic studies reveal that the
      phosphoserine/phosphothreonine recognition site of the polo-box domain is the
      binding pocket for thymoquinone and its analogue poloxime. Both small molecules
      displace phosphopeptides bound with the polo-box domain in a slow but noncovalent
      binding mode. A conserved water bridge and a cation-pi interaction were found as
      their competition strategy against the phosphate group. This mechanism sheds
      light on small-molecule intervention of phospho-recognition by the polo-box
      domain of polo-like kinase 1 and other phospho-binding proteins in general.

PMID- 23135291
TI  - Brachial amyotrophic diparesis associated with anti-Hu positive anterior horn
      cell disease and autonomic disorder.

PMID- 23135292
TI  - Olfactory bulb volume in patients with temporal lobe epilepsy.
AB  - The study aimed to investigate the volume of the olfactory bulb (OB) in patients
      with temporal lobe epilepsy (TLE). Specifically, we wanted to see whether the
      olfactory deficit typically found in TLE patients also exerts a top-down
      influence on the OB. Twenty patients, and 20 age- and sex-matched healthy
      controls underwent olfactory testing by means of the Sniffin' Sticks testing
      device (measurement of odor threshold, and identification abilities). In
      addition, they underwent an MR scan with 2-mm-thick T2-weighted fast spin-echo
      images without interslice gap in the coronal plane covering the anterior and
      middle segments of the base of the skull. Olfactory function was significantly
      impaired in TLE patients compared to healthy controls both at threshold level and
      for odor identification (p < 0.001); in addition, OB volumes were smaller than in
      controls (p = 0.013). The deficit seen at the level of the OB did not correlate
      with the side of the epileptic focus. Assuming that the olfactory deficit in TLE
      patients is due to the central nervous epileptic focus it appears that the OB
      volume is not only subject to changes in the periphery of the olfactory system,
      but also changes as a consequence to changes at a cortical level.

PMID- 23135295
TI  - Pathology in context.

PMID- 23135297
TI  - Response to Guest Editorial ("Veterinary pathology under the microscope: planning
      for the future").

PMID- 23135296
TI  - Meeting report: Spontaneous lesions and diseases in wild, captive-bred, and zoo
      housed nonhuman primates and in nonhuman primate species used in drug safety
      studies.
AB  - The combination of loss of habitat, human population encroachment, and increased
      demand of select nonhuman primates for biomedical research has significantly
      affected populations. There remains a need for knowledge and expertise in
      understanding background findings as related to the age, source, strain, and
      disease status of nonhuman primates. In particular, for safety/biomedical
      studies, a broader understanding and documentation of lesions would help clarify
      background from drug-related findings. A workshop and a minisymposium on
      spontaneous lesions and diseases in nonhuman primates were sponsored by the
      concurrent Annual Meetings of the American College of Veterinary Pathologists and
      the American Society for Veterinary Clinical Pathology held December 3-4, 2011,
      in Nashville, Tennessee. The first session had presentations from Drs Lowenstine
      and Montali, pathologists with extensive experience in wild and zoo populations
      of nonhuman primates, which was followed by presentations of 20 unique case
      reports of rare or newly observed spontaneous lesions in nonhuman primates (see
      online files for access to digital whole-slide images corresponding to each case
      report at
      http://www.scanscope.com/ACVP%20Slide%20Seminars/2011/Primate%20Pathology/view.ap
      l). The minisymposium was composed of 5 nonhuman-primate researchers (Drs
      Bradley, Cline, Sasseville, Miller, Hutto) who concentrated on background and
      spontaneous lesions in nonhuman primates used in drug safety studies. Cynomolgus
      and rhesus macaques were emphasized, with some material presented on common
      marmosets. Congenital, acquired, inflammatory, and neoplastic changes were
      highlighed with a focus on clinical, macroscopic, and histopathologic findings
      that could confound the interpretation of drug safety studies.

PMID- 23135299
TI  - Predictive ability of sleep duration for the feeling of being refreshed by sleep.

PMID- 23135301
TI  - The impact of the Worksite Heart Health Improvement Project on work ability: a
      pilot study.
AB  - OBJECTIVE: To test the efficacy of the Worksite Heart Health Improvement Project
      (WHHIP). METHODS: The WHHIP was a quasi-experimental, 6-month pilot performed in
      two long-term care facilities. Thirty-nine minority female nursing assistants
      participated in this study. The 3-month WHHIP intervention focused on reducing
      cardiovascular disease risk by increasing physical activity and reducing the
      amount of salt and fat consumed. The intervention included three components:
      environmental and policy assessment; education; and ongoing motivation. The
      control site received education only. Measures were collected at baseline, 3
      months, and 6 months and included work ability, job stress, and job satisfaction.
      RESULTS: Generalized estimating equations showed that the treatment group
      demonstrated significant improvements in work ability (P = 0.049). CONCLUSIONS:
      There was preliminary evidence that the WHHIP improved work ability, and future
      research should assess the impact of improved work ability on patients.

PMID- 23135302
TI  - How does an occupational neurologist assess welders and steelworkers for a
      manganese-induced movement disorder? An international team's experiences in
      Guanxi, China, part I.

PMID- 23135305
TI  - Flow cytometric analysis of in vitro cytotoxicity of cadmium in haemocytes from
      the tiger shrimp, Penaeus monodon.
AB  - This study investigated the toxic effects of cadmium on viability, reactive
      oxygen species (ROS) production and non-specific esterase activity of Penaeus
      monodon haemocytes in vitro, using a flow cytometric assay. After 6 h in vitro
      exposure with 10(-9)-10(-3) M Cd(2+), cell viability, ROS production and esterase
      activity of haemocytes from P. monodon were determined. Results showed that at
      the lowest exposures (10(-9)-10(-6 )M), Cd(2+) induced no effect on cell
      viability, ROS production and esterase activity. At a higher level (10(-5) M) of
      exposure, production of ROS was stimulated while Cd(2+) had no effect on cell
      viability and esterase activity. At the two highest concentrations (10(-4) and
      10(-3) M), Cd(2+) caused increased ROS production, cell death and inhibited
      esterase activity. These results showed a relationship between Cd(2+) exposure
      dose and its cytotoxicity on shrimp haemocytes. Cadmium was cytotoxic and
      immunotoxic for P. monodon haemocytes in vitro when the dose reached 10(-4) M.
      The study also suggested that flow cytometry could be used as a tool for
      cytotoxic research of aquatic contamination on shrimp.

PMID- 23135306
TI  - The effect of heavy metal concentration and soil pH on the abundance of selected
      microbial groups within ArcelorMittal Poland steelworks in Cracow.
AB  - The present study aimed to identify the effect of heavy metal concentration and
      soil pH on the abundance of the selected soil microorganisms within ArcelorMittal
      Poland steelworks, Cracow. The analysis included 20 soil samples, where the
      concentration of Fe, Zn, Cd, Pb, Ni, Cu, Mn, Cr and soil pH were evaluated
      together with the number of mesophilic bacteria, fungi, Actinomycetes and
      Azotobacter spp. In the majority of samples soil pH was alkaline. The limits of
      heavy metals exceeded in eight samples and in one sample, the concentration of Zn
      exceeded 31-fold. Chromium was the element which most significantly limited the
      number of bacteria and Actinomycetes.

PMID- 23135307
TI  - Field dissipation of metamitron in soil and sugar beet crop.
AB  - Bioaccumulation of herbicides in plant produce may cause ailing effect on animals
      and human beings through food chain contamination. Thus oblige the investigation
      of newer herbicide metamitron for its persistence and degradation in sugar beet
      crop and soil. Metamitron persist in plant up to 15 days while up to 30 days in
      soil. Its dissipation followed first order reaction kinetics. On day 90,
      metamitron was detected in the soil at 7.0 kg a.i. ha(-1) treated plot only. It
      would be concluded that metamitron at 3.5 kg a.i. ha(-1) can be safely applied to
      the sugar beet crop for weed control.

PMID- 23135309
TI  - Comorbid bipolar disorder and premenstrual dysphoric disorder: real patients,
      unanswered questions.
AB  - Large-scale clinical and epidemiological studies suggest a link between bipolar
      disorder (BD) and premenstrual dysphoric disorder (PMDD). However, smaller
      studies using prospective charting failed to find this association. Here, we
      report three cases of individuals with BD and comorbid PMDD who responded
      successfully to adjunctive contraceptive agents in the management of their severe
      premenstrual symptoms. While controlled trials investigating pharmacological and
      non-pharmacological treatments are awaited, adjunctive treatment of contraceptive
      agents and mood stabilizers may be an option in the treatment of comorbid BD and
      PMDD.

PMID- 23135310
TI  - Benzothiadiazole-containing donor-acceptor-acceptor type organic sensitizers for
      solar cells with ZnO photoanodes.
AB  - Dye-sensitized solar cells using nanocrystalline ZnO as the photoanode and a
      metal-free sensitizer with a benzothiadiazole entity directly connected to the 2
      cyanoacrylic acid acceptor exhibited an efficiency (5.18%) higher than those
      using the TiO(2) photoanode. Use of a hierarchical ZnO back scattering layer
      further improved the efficiency to 5.82%.

PMID- 23135311
TI  - Factors influencing surgical and adjuvant therapy in stage I breast cancer: a
      SEER 18 database analysis.
AB  - BACKGROUND: Randomized trials have shown no survival difference for patients with
      stage I breast cancer treated with mastectomy versus breast-conserving surgery
      (BCS) with radiotherapy (RT). RT is recommended after BCS in order to decrease
      local recurrence and mortality. We sought to evaluate the treatment trends in
      patients with stage I breast cancer. METHODS: We used the Surveillance,
      Epidemiology, and End Results (SEER) database to identify 194,860 women with
      stage I breast cancer diagnosed from 1988 to 2007. We evaluated factors that were
      associated surgical treatment and the utilization of RT after BCS. RESULTS: There
      was a progressive decline in the proportion of patients with stage I breast
      cancer who were treated with mastectomy from 1998 to 2007. Significant predictors
      for being treated with mastectomy included single/divorced women (p = 0.007),
      white race (p < 0.001), estrogen receptor negativity (p < 0.001), earlier year of
      diagnosis (p < 0.001), smaller tumor size (p < 0.001), and region (p < 0.001).
      Twenty percent of the BCS cohort did not receive RT, and this proportion did not
      change over time. Significant predictors for not receiving RT included small
      tumor size (p < 0.001), African American race (p < 0.001), increasing age (p <
      0.001), single/divorced women (p < 0.001), estrogen receptor negativity (p <
      0.001), and region (p < 0.001). The survival for patients treated with BCS and RT
      was significantly higher than for those who did not receive RT (p < 0.001).
      CONCLUSIONS: The use of BCS for the treatment of stage I breast cancer increased
      over time. A constant proportion of patients did not receive RT after BCS.
      Omission of RT in BCS is associated with an increase in mortality.

PMID- 23135312
TI  - Increasing national mastectomy rates for the treatment of early stage breast
      cancer.
AB  - BACKGROUND: To study national trends in the mastectomy rate for treatment of
      early stage breast cancer. METHODS: We analyzed data from the Surveillance,
      Epidemiology, and End Results database, including 256,081 women diagnosed with T1
      2 N0-3 M0 breast cancer from 2000 to 2008. We evaluated therapeutic mastectomy
      rates by the year of diagnosis and performed a multivariable logistic regression
      analyses to determine predictors of mastectomy as the treatment choice. RESULTS:
      The proportion of women treated with mastectomy decreased from 40.1 to 35.6 %
      between 2000 and 2005. Subsequently, the mastectomy rate increased to 38.4 % in
      2008 (p < 0.0001). Simple logistic regression models demonstrated that mastectomy
      rates between 2005 and 2008 were moderated by age (p < 0.0001), marital status (p
      = 0.0230), and geographic location (p < 0.0001). Multivariate logistic regression
      analysis found that age, race, marital status, geographic location, involvement
      of multiple regions of the breast, lobular histology, increasing T stage, lymph
      node positivity, increasing grade, and negative hormone receptor status were
      independent predictors of mastectomy. Additionally, multivariate analysis
      confirmed that women diagnosed in 2008 were more likely to undergo mastectomy
      than women diagnosed in 2005 (odds ratio 1.17, 95 % confidence interval 1.13 to
      1.21, p < 0.0001). CONCLUSIONS: There is evidence of a reversal in the previously
      declining national mastectomy rates, with the mastectomy rate reaching a nadir in
      2005 and subsequently rising. Further follow-up to confirm this trend and
      investigation to determine the underlying cause of this trend and its effect on
      outcomes may be warranted.

PMID- 23135313
TI  - Progression of non-small cell lung cancer: diagnostic and prognostic utility of
      matrix metalloproteinase-2, C-reactive protein and serum amyloid A.
AB  - Matrix metalloproteinase-2 (MMP-2) is known to degrade type IV collagen, which is
      a major component of the cellular basement membrane, and to be involved in the
      invasion and metastasis of cancer cells. On the other hand, C-reactive protein
      (CRP) and serum amyloid A (SAA) are acute inflammatory biomarkers that increase
      in various conditions including infection, inflammation, malignancy and tissue
      disturbance. In the present study, we examined the serum levels of MMP-2, CRP and
      SAA in patients with localized and metastatic non-small cell lung cancer (NSCLC)
      to establish the clinical significance and changes in these biomarkers during
      NSCLC progression. In this study, 24 NSCLC patients were diagnosed at the
      Kitasato University Hospital and compared with 13 healthy controls. Measurement
      of MMP-2 levels in serum was determined by measuring pro-MMP-2 using a one-step
      sandwich enzyme immunoassay. CRP and SAA levels in the serum were measured by
      latex nephelometry. The serum levels of MMP-2, CRP and SAA in metastatic NSCLC
      patients were significantly higher than in localized NSCLC patients (p<0.01).
      There was a significant positive correlation between serum MMP-2 and CRP levels
      as well as SAA levels in metastatic NSCLC patients (p<0.01). Therefore,
      quantitation of MMP-2, CRP and SAA in NSCLC patients may be an auxiliary
      indicator to monitor tumor progression and poor prognosis of NSCLC disease.

PMID- 23135314
TI  - Characterization of polarized THP-1 macrophages and polarizing ability of LPS and
      food compounds.
AB  - Little is known about the polarizing potential of currently used human macrophage
      cell lines, while a better understanding phenomena can support the prediction of
      effects in vivo based on in vitro analysis. To test the polarization capability
      of PMA differentiated-THP-1 macrophages (M0), cells were stimulated with 20 ng
      ml(-1) IFNgamma + 1 MUg ml(-1) LPS and 20 ng ml(-1) IL-4, which are known to
      influence macrophage polarization in vivo and ex vivo into the M1 and M2 state,
      respectively. Apart from several well-known M1 and M2 markers, also new possible
      markers for M1 and M2 polarization were analysed in this study. The expression of
      M1 marker genes was up-regulated in IFNgamma + LPS stimulated-M0 THP-1
      macrophages. The IL-4 stimulated-M0 THP-1 macrophages expressed M2 cell membrane
      receptor genes. However, M2 chemokine and their receptor genes were only slightly
      up-regulated which might be due to the complexity of the secondary cell-cell
      interaction of the chemokine system. Lipopolysaccharides from E. coli (LPS) and
      food compounds [lentinan, vitamin D3 (vD3) and the combination of lentinan +
      vitamin D3 (Len + vD3)] were investigated for their polarizing ability on M0 THP
      1 macrophages towards either the M1 or M2 state. LPS (700 ng ml(-1)) was able to
      skew M0 THP-1 macrophages towards the M1 direction since all analysed M1 marker
      genes were strongly expressed. Lentinan, vD3 and Len + vD3 did not induce
      expression of either M1 or M2 markers, indicating no polarizing ability of these
      compounds. Based on the expression of M1 and M2 marker genes we concluded that
      THP-1 macrophages could be successfully polarized into either the M1 or M2 state.
      Therefore, they can be used as a new macrophage polarizing model to estimate the
      polarizing/switching ability of test food compounds.

PMID- 23135315
TI  - Experimental demonstration of benchtop x-ray fluorescence computed tomography
      (XFCT) of gold nanoparticle-loaded objects using lead- and tin-filtered
      polychromatic cone-beams.
AB  - This report presents the first experimental demonstration, to our knowledge, of
      benchtop polychromatic cone-beam x-ray fluorescence computed tomography (XFCT)
      for a simultaneous determination of the spatial distribution and amount of gold
      nanoparticles (GNPs) within small-animal-sized objects. The current benchtop
      experimental setup successfully produced XFCT images accurately showing the
      regions containing small amount of GNPs (on the order of 0.1 mg) within a 3 cm
      diameter plastic phantom. In particular, the performance of the current XFCT
      setup was improved remarkably (e.g., at least a factor of 3 reduction in XFCT
      scan time) using a tin-filtered polychromatic beam in comparison with a lead
      filtered beam. The results of this study strongly suggest that the current
      benchtop XFCT configuration can be made practical with a few modifications such
      as the deployment of array detectors, while meeting realistic constraints on x
      ray dose, scan time and image resolution for routine pre-clinical in vivo imaging
      with GNPs.

PMID- 23135316
TI  - Hydration of arsenic oxyacid species.
AB  - The bond distances in hydrated arsenic oxyacid species in aqueous solution have
      been studied by EXAFS spectroscopy and large angle X-ray scattering, LAXS. These
      results have been compared to structures in the solid state, as found in an
      extensive survey of available crystal structures. Protonated oxygen atoms can be
      distinguished with a longer As-O distance for both arsenic(V) and arsenic(III)
      species in the crystalline state. However, the average As-O distance for the
      H(n)AsO(4)((3-n)-) species (0 <=n<= 3) remains the same. These average values are
      slightly shorter, ca. 0.02 A, than in aqueous solution due to the hydration as
      determined by EXAFS and LAXS. The K absorption edges for arsenic(V) and
      arsenic(III) species are separated by 4.0 eV, and the shape of the absorption
      edges differs as well. Small but significant differences in the absorption edge
      features are seen between the neutral acids and the charged oxyacid species. The
      most important arsenic species from an environmental point of view is arsenous
      acid, As(OH)(3). In addition to arsenous acid, we have used orthotelluric acid,
      Te(OH)(6), for comparison with arsenous acid and for detailed studies of the
      hydration of covalently bound hydroxo groups. Arsenous acid cannot be studied
      with the same accuracy as orthotelluric acid, due to a relatively low solubility
      of As(2)O(3)(s) in neutral to acidic aqueous solution. The results from the DDIR
      studies support the assignment of As(OH)(3) as a weak structure maker analogous
      to Te(OH)(6), both being neutral weak oxyacids.

PMID- 23135317
TI  - A retrospective study of amitriptyline in youth with autism spectrum disorders.
AB  - We performed a retrospective chart review of 50 youths with Autism Spectrum
      Disorder (ASD), prescribed amitriptyline (AMI) for hyperactivity and impulsivity.
      Data was systematically extracted from 50 outpatient clinic charts, including AMI
      treatment duration, dose, trough levels and adverse events. Mean age was 9.4
      years (4.6-17.9); 40 were males and 10 females. 30 % had failed atomoxetine and
      40 % had failed >=3 ADHD medications. Mean dose was 1.3 +/- 0.6 mg/kg/day, mean
      trough level 114.1 +/- 50.5 ng/ml, mean duration 3.4 years. Clinical Global
      Impressions Scale-Improvement (CGI-I) was <=2 in 60 % of patients at the final
      visit, and in 82 % of patients for at least 50 % of follow-ups. Cautious use of
      low dose AMI shows promise for treatment-resistant youth with ASD accompanied by
      hyperactivity, impulsivity, aggression and self injury.

PMID- 23135318
TI  - Serum undercarboxylated osteocalcin level increases with 48 weeks of teriparatide
      treatment in pre-treated elderly rheumatoid arthritis patients who use anti
      resorptive drugs.
AB  - AIM: The serum undercarboxylated osteocalcin (ucOC) level, a biochemical bone
      marker of vitamin K insufficiency, is often affected by anti-osteoporosis drugs.
      There have been no reports regarding the relationship between ucOC and
      teriparatide. SUBJECTS AND METHODS: We conducted a prospective observational
      study of 26 female rheumatoid arthritis (RA) patients. The patients were divided
      into 3 groups: those who underwent a direct switch from anti-resorptive drugs to
      teriparatide (12 cases), those who started teriparatide without pre-treatment (5
      cases), and the control patients (9 cases). The median age (interquartile range)
      of the patients in each group was 75 (67-77), 82 (78-84), and 69 (62-80) yr,
      respectively. All patients, except controls, received 48-week treatments of
      teriparatide. We analyzed the median 48-week changes from baseline of the serum
      ucOC levels with the Steel-Dwass method. RESULTS: The median change from baseline
      in the direct switch group was higher than that in other groups (p<0.05).
      CONCLUSIONS: The serum ucOC levels increased with treatment of teriparatide in
      elderly RA patients, especially when the patients received pre-treatment.

PMID- 23135319
TI  - Asymmetric dimethylarginine and carotid atherosclerosis in Type 2 diabetes
      mellitus.
AB  - BACKGROUND: Circulating asymmetric dimethylarginine (ADMA) concentration is
      elevated in patients with Type 2 diabetes mellitus (T2DM). AIM: To assess the
      relationship between plasma ADMA concentration and carotid atherosclerosis in
      patients with T2DM. SUBJECTS AND METHODS: A total of 72 newly diagnosed and
      untreated T2DM individuals and 72 healthy controls were studied. Carotid
      atherosclerosis was determined by ultrasonographically evaluated intima- media
      thickness (IMT) and plaque score. Plasma concentration of ADMA was measured by
      high-performance liquid chromatography. RESULTS: Plasma ADMA, mean IMT, and
      plaque score were higher in diabetic patients compared with controls. Univariate
      and multivariate analyses demonstrated an independent association between ADMA
      and mean IMT in diabetic patients. On a multiple logistic regression analysis,
      ADMA was the sole predictor of carotid plaque formation (plaque score >=1.1)
      (odds ratio 2.43, 95% confidence interval 1.19 to 4.94, p<0.05). CONCLUSION: Our
      results suggest that increased levels of ADMA might be involved in the
      development of carotid atherosclerosis in T2DM.

PMID- 23135320
TI  - Endocrinology and art. Giacomo Francesco Cipper called Todeschini (1664-1736) -
      Head of a man in blue.

PMID- 23135321
TI  - Evaluation in vitro and in animals of a new 11C-labeled PET radioligand for
      metabotropic glutamate receptors 1 in brain.
AB  - PURPOSE: Two allosteric modulators of the group I metabotropic glutamate
      receptors (mGluR1 and mGluR5) were evaluated as positron emission tomography
      (PET) radioligands for mGluR1. METHODS: LY2428703, a full mGluR1 antagonist
      (IC(50) 8.9 nM) and partial mGluR5 antagonist (IC(50) 118 nM), and LSN2606428, a
      full mGluR1 and mGluR5 antagonist (IC(50) 35.3 nM and 10.2 nM, respectively) were
      successfully labeled with (11)C and evaluated as radioligands for mGluR1. The
      pharmacology of LY2428703 was comprehensively assessed in vitro and in vivo, and
      its biodistribution was investigated by liquid chromatography-mass
      spectrometry/mass spectrometry, and by PET imaging in the rat. In contrast,
      LSN2606428 was only evaluated in vitro; further evaluation was stopped due to its
      unfavorable pharmacological properties and binding affinity. RESULTS: (11)C
      LY2428703 showed promising characteristics, including: (1) high potency for
      binding to human mGluR1 (IC(50) 8.9 nM) with no significant affinity for other
      human mGlu receptors (mGluR2 through mGluR8); (2) binding to brain displaceable
      by administration of an mGluR1 antagonist; (3) only one major radiometabolite in
      both plasma and brain, with a negligible brain concentration (with 3.5 % of the
      total radioactivity in cerebellum) and no receptor affinity; (4) a large specific
      and displaceable signal in the mGluR1-rich cerebellum with no significant in vivo
      affinity for mGluR5, as shown by PET studies in rats; and (5) lack of substrate
      behavior for efflux transporters at the blood-brain barrier, as shown by PET
      studies conducted in wild-type and knockout mice. CONCLUSION: (11)C-LY2428703, a
      new PET radioligand for mGluR1 quantification, displayed promising
      characteristics both in vitro and in vivo in rodents.

PMID- 23135322
TI  - In vivo imaging of induction of heat-shock protein-70 gene expression with
      fluorescence reflectance imaging and intravital confocal microscopy following
      brain ischaemia in reporter mice.
AB  - PURPOSE: Stroke induces strong expression of the 72-kDa heat-shock protein (HSP
      70) in the ischaemic brain, and neuronal expression of HSP-70 is associated with
      the ischaemic penumbra. The aim of this study was to image induction of Hsp-70
      gene expression in vivo after brain ischaemia using reporter mice. METHODS: A
      genomic DNA sequence of the Hspa1b promoter was used to generate an Hsp70-mPlum
      far-red fluorescence reporter vector. The construct was tested in cellular
      systems (NIH3T3 mouse fibroblast cell line) by transient transfection and
      examining mPlum and Hsp-70 induction under a challenge. After construct
      validation, mPlum transgenic mice were generated. Focal brain ischaemia was
      induced by transient intraluminal occlusion of the middle cerebral artery and the
      mice were imaged in vivo with fluorescence reflectance imaging (FRI) with an
      intact skull, and with confocal microscopy after opening a cranial window.
      RESULTS: Cells transfected with the Hsp70-mPlum construct showed mPlum
      fluorescence after stimulation. One day after induction of ischaemia, reporter
      mice showed a FRI signal located in the HSP-70-positive zone within the
      ipsilateral hemisphere, as validated by immunohistochemistry. Live confocal
      microscopy allowed brain tissue to be visualized at the cellular level. mPlum
      fluorescence was observed in vivo in the ipsilateral cortex 1 day after induction
      of ischaemia in neurons, where it is compatible with penumbra and neuronal
      viability, and in blood vessels in the core of the infarction. CONCLUSION: This
      study showed in vivo induction of Hsp-70 gene expression in ischaemic brain using
      reporter mice. The fluorescence signal showed in vivo the induction of Hsp-70 in
      penumbra neurons and in the vasculature within the ischaemic core.

PMID- 23135323
TI  - Editorial principles and practices of GENETICS: a peer-edited journal of the
      Genetics Society of America.

PMID- 23135324
TI  - Genome evolution due to allopolyploidization in wheat.
AB  - The wheat group has evolved through allopolyploidization, namely, through
      hybridization among species from the plant genera Aegilops and Triticum followed
      by genome doubling. This speciation process has been associated with
      ecogeographical expansion and with domestication. In the past few decades, we
      have searched for explanations for this impressive success. Our studies attempted
      to probe the bases for the wide genetic variation characterizing these species,
      which accounts for their great adaptability and colonizing ability. Central to
      our work was the investigation of how allopolyploidization alters genome
      structure and expression. We found in wheat that allopolyploidy accelerated
      genome evolution in two ways: (1) it triggered rapid genome alterations through
      the instantaneous generation of a variety of cardinal genetic and epigenetic
      changes (which we termed "revolutionary" changes), and (2) it facilitated
      sporadic genomic changes throughout the species' evolution (i.e., evolutionary
      changes), which are not attainable at the diploid level. Our major findings in
      natural and synthetic allopolyploid wheat indicate that these alterations have
      led to the cytological and genetic diploidization of the allopolyploids. These
      genetic and epigenetic changes reflect the dynamic structural and functional
      plasticity of the allopolyploid wheat genome. The significance of this plasticity
      for the successful establishment of wheat allopolyploids, in nature and under
      domestication, is discussed.

PMID- 23135327
TI  - Nickel-catalyzed C-P cross-coupling of diphenylphosphine oxide with aryl
      chlorides.
AB  - A novel protocol for the preparation of various diarylphosphine oxide compounds
      via a Ni-catalyzed cross-coupling of aryl chlorides with R(2)P(O)H has been
      developed. Notably, this process exhibits the following very attractive features:
      (i) the process is simpler and operates under mild reaction conditions; (ii) the
      process is generally cheaper in part because the more accessible aryl chloride is
      used to form the C-P bond; (iii) the process avoids the need for simultaneous
      preparation and use of Ar(2)P(O)M.

PMID- 23135328
TI  - A mitochondrial alkaline/neutral invertase isoform (A/N-InvC) functions in
      developmental energy-demanding processes in Arabidopsis.
AB  - Recent findings demonstrate that alkaline/neutral invertases (A/N-Invs), enzymes
      that catalyze the breakdown of sucrose into glucose and fructose, are essential
      proteins in plant life. The fact that different isoforms are present in multiple
      locations makes them candidates for the coordination of metabolic processes. In
      the present study, we functionally characterized the encoding gene of a novel A/N
      Inv (named A/N-InvC) from Arabidopsis, which localizes in mitochondria. A/N-InvC
      is expressed in roots, in aerial parts (shoots and leaves) and flowers. A
      detailed phenotypic analysis of knockout mutant plants (invc) reveals an impaired
      growth phenotype. Shoot growth was severely reduced, but root development was not
      affected as reported for A/N-InvA mutant (inva) plants. Remarkably, germination
      and flowering, two energy demanding processes, were the most affected stages. The
      effect of exogenous growth regulators led us to suggest that A/N-InvC may be
      modulating hormone balance in relation to the radicle emergence. We also show
      that oxygen consumption is reduced in inva and invc in comparison with wild-type
      plants, indicating that both organelle isoenzymes may play a fundamental role in
      mitochondrion functionality. Taken together, our results emphasize the
      involvement of mitochondrial A/N-Invs in developmental processes and uncover the
      possibility of playing different roles for the two isoforms located in the
      organelle.

PMID- 23135329
TI  - Transcriptome sequencing of the Antarctic vascular plant Deschampsia antarctica
      Desv. under abiotic stress.
AB  - Antarctic hairgrass (Deschampsia antarctica Desv.) is the only natural grass
      species in the maritime Antarctic. It has been studied as an extremophile that
      has successfully adapted to marginal land with the harshest environment for
      terrestrial plants. However, limited genetic research has focused on this species
      due to the lack of genomic resources. Here, we present the first de novo assembly
      of its transcriptome by massive parallel sequencing and its expression profile
      using D. antarctica grown under various stress conditions. Total sequence reads
      generated by pyrosequencing were assembled into 60,765 unigenes (28,177 contigs
      and 32,588 singletons). A total of 29,173 unique protein-coding genes were
      identified based on sequence similarities to known proteins. The combined results
      from all three stress conditions indicated differential expression of 3,110
      genes. Quantitative reverse transcription polymerase chain reaction showed that
      several well-known stress-responsive genes encoding late embryogenesis abundant
      protein, dehydrin 1, and ice recrystallization inhibition protein were induced
      dramatically and that genes encoding U-box-domain-containing protein, electron
      transfer flavoprotein-ubiquinone, and F-box-containing protein were induced by
      abiotic stressors in a manner conserved with other plant species. We identified
      more than 2,000 simple sequence repeats that can be developed as functional
      molecular markers. This dataset is the most comprehensive transcriptome resource
      currently available for D. antarctica and is therefore expected to be an
      important foundation for future genetic studies of grasses and extremophiles.

PMID- 23135330
TI  - Protein micro-structuring as a tool to texturize protein foods.
AB  - Structuring protein foods to control the textural properties receives growing
      attention nowadays. It requires decoupling of the product properties such as
      water holding capacity and the mechanical properties from the actual protein
      concentration in the product. From an application point of view, both increasing
      and lowering the protein content in the food are interesting. Foods enriched with
      proteins are important due to their reported health benefits, but increasing the
      protein content in food products generally leads to products that are firmer and
      have a more rubbery mouth-feel than the regular products, making them less
      attractive. A reduced protein content, for example in meat- or cheese-analogues,
      is relevant because it leads to a lower caloric intake per serving and it
      enhances its economic potential. Decoupling of the protein concentration and
      product properties can be obtained by changing the internal structure of those
      food products. This paper outlines the use of protein aggregates and particles in
      a protein matrix as a tool to obtain different textural properties of a model
      protein product. Whey protein isolate (WPI) was taken as a model protein.
      However, further investigation of WPI microparticles should focus on a better
      understanding of their swelling behaviour in the protein matrix to fully use the
      potential of those protein particles as a tool to decouple product properties and
      actual protein concentration.

PMID- 23135331
TI  - Lateral impact validation of a geometrically accurate full body finite element
      model for blunt injury prediction.
AB  - This study presents four validation cases of a mid-sized male (M50) full human
      body finite element model-two lateral sled tests at 6.7 m/s, one sled test at 8.9
      m/s, and a lateral drop test. Model results were compared to transient force
      curves, peak force, chest compression, and number of fractures from the studies.
      For one of the 6.7 m/s impacts (flat wall impact), the peak thoracic, abdominal
      and pelvic loads were 8.7, 3.1 and 14.9 kN for the model and 5.2 +/- 1.1 kN, 3.1
      +/- 1.1 kN, and 6.3 +/- 2.3 kN for the tests. For the same test setup in the 8.9
      m/s case, they were 12.6, 6, and 21.9 kN for the model and 9.1 +/- 1.5 kN, 4.9 +/
      1.1 kN, and 17.4 +/- 6.8 kN for the experiments. The combined torso load and the
      pelvis load simulated in a second rigid wall impact at 6.7 m/s were 11.4 and 15.6
      kN, respectively, compared to 8.5 +/- 0.2 kN and 8.3 +/- 1.8 kN experimentally.
      The peak thorax load in the drop test was 6.7 kN for the model, within the range
      in the cadavers, 5.8-7.4 kN. When analyzing rib fractures, the model predicted
      Abbreviated Injury Scale scores within the reported range in three of four cases.
      Objective comparison methods were used to quantitatively compare the model
      results to the literature studies. The results show a good match in the thorax
      and abdomen regions while the pelvis results over predicted the reaction loads
      from the literature studies. These results are an important milestone in the
      development and validation of this globally developed average male FEA model in
      lateral impact.

PMID- 23135333
TI  - Patient safety culture-perception of health care workers in a tertiary care
      hospital.
AB  - BACKGROUND AND OBJECTIVES: Patient safety is a discipline that emphasizes the
      reporting, analysis and prevention of medical errors leading to adverse events.
      Many patients are harmed from health care, resulting in permanent injury,
      increased hospital stay or even death. This study attempts to gain knowledge on
      the practices and attitude existing for patient safety and indicate knowledge
      gaps, to help improve the situation. METHODS: The study was carried out using an
      anonymous, self reporting questionnaire structured to analyse the scenario of
      patient safety in the hospital and the attitude of 100 Healthcare workers towards
      safety. RESULTS: Of the subjects included in the study, only 55% knew of the
      existence of an infection control policy in the institution. A large majority of
      respondents (94%) believed that reporting of errors will help in reducing their
      incidence. Top reasons for adverse events were high workload (82%) and incomplete
      information from patients (71%). INTERPRETATION AND CONCLUSIONS: Patient safety
      is still in its infant stages in India, despite the emphasis by WHO. The problem
      areas, including high work load, lack of communication by supervisory staff and
      recording of 'near-miss' and adverse events with feedback, if addressed, would
      minimise harm to patients and cut costs.

PMID- 23135325
TI  - Architecture and biosynthesis of the Saccharomyces cerevisiae cell wall.
AB  - The wall gives a Saccharomyces cerevisiae cell its osmotic integrity; defines
      cell shape during budding growth, mating, sporulation, and pseudohypha formation;
      and presents adhesive glycoproteins to other yeast cells. The wall consists of
      beta1,3- and beta1,6-glucans, a small amount of chitin, and many different
      proteins that may bear N- and O-linked glycans and a glycolipid anchor. These
      components become cross-linked in various ways to form higher-order complexes.
      Wall composition and degree of cross-linking vary during growth and development
      and change in response to cell wall stress. This article reviews wall biogenesis
      in vegetative cells, covering the structure of wall components and how they are
      cross-linked; the biosynthesis of N- and O-linked glycans,
      glycosylphosphatidylinositol membrane anchors, beta1,3- and beta1,6-linked
      glucans, and chitin; the reactions that cross-link wall components; and the
      possible functions of enzymatic and nonenzymatic cell wall proteins.

PMID- 23135334
TI  - Patient handoffs: Delivering content efficiently and effectively is not enough.
AB  - BACKGROUND: The transfer of care from one provider to another is fraught with
      potential failures. Unfortunately the consequences of a poorly conducted patient
      handoff can be quite high. In the last five years there have been many
      descriptions of this problem as well as suggested solutions. Commonly authors
      have focused on utilization of a formatted tool for the off-going provider to
      help improve patient handoffs. While this is certainly a requirement for a high
      quality transfer of care, it is not the only needed component. OBJECTIVES: We
      seek to describe a novel approach to handoffs and focus on the early findings
      from our pilot projects. METHODS: The handoff typically involves two clinicians;
      an off-going or sending provider and an oncoming or receiving provider, there are
      therefore dual responsibilities in performing a high quality handoff. The off
      going provider should structure their patient handoff in an easily assimilable
      format as earlier work has described. However a high quality handoff also needs
      to set the expectation that the oncoming provider must be certain that they have
      heard the relevant patient information. Therefore a tool to assist with this
      process is warranted. We describe our early experience of utilization of a
      structured handoff receiver tool. RESULTS: Clinicians report higher quality
      handoffs as a result of the addition of the dual responsibility handoff. Use of
      the I-5 Tool improved transfer of care. Also early results suggest that there are
      failures in care that would have occurred without this intervention. CONCLUSIONS:
      Early results from pilot testing reveal after designing and testing the dual
      responsibility model that patient handoffs are increasingly successful and more
      reliable.

PMID- 23135335
TI  - A novel system of prescribing feedback to reduce errors: A pilot study.
AB  - BACKGROUND: Prescribing errors are one of the most common adverse events in
      healthcare. Previous research in patient safety has highlighted the importance of
      error awareness education to enhance professional attitudes and reduce errors.
      Systems of contemporaneous prescribing feedback previous researched are limited
      by shift working. OBJECTIVES: We introduced a departmental prescribing feedback
      system to address this limitation. METHODS: We used a Before and After study
      design. The setting was a single inpatient paediatric unit and 26 Paediatric
      medical staff participated. Baseline assessment of prescribing errors and safety
      attitudes took place, followed by 3 weekly reassessments over a 3 month period.
      After each assessment, a feedback poster was displayed and emailed to staff,
      giving general and anonymous personalised feedback. RESULTS: 205 medication
      orders representing 3,280 opportunities for error were examined. There was a
      statistically significant reduction in the error rate (P < 0.0001) between
      baseline (8.8%, 69 out of 784 possibilities for error) and completion at 3 months
      (1.8%, 12 out of 656 possibilities for error). There was an improvement in
      patient safety attitudes, but this was not statistically significant.
      CONCLUSIONS: This pilot project has demonstrated an error feedback system can
      reduce errors. This technique could be easily adopted and introduced, warranting
      further research.

PMID- 23135336
TI  - Severe muscle symptoms with lipid-lowering agents may be confused with neurogenic
      claudication associated with spinal canal stenosis.
AB  - BACKGROUND: Screening of the WHO global individual case safety report database
      (VigiBase) has recently identified case reports with HMG CoA reductase inhibitors
      and muscle symptoms co-reported with spinal stenosis. In some reports spinal
      stenosis appears to have been listed as a coincidental finding. OBJECTIVE: To
      assess reports with sufficient information to ascertain if they suggested that
      there may have been diagnostic confusion between muscle symptoms attributable to
      HMG CoA reductase inhibitors with or without ezetimibe and symptoms of spinal
      stenosis. METHOD: Reports were examined for patient demographics, past history,
      clinical and investigational findings, co-prescribed medicines and outcomes.
      RESULTS: Three case histories recorded details suggestive of diagnostic confusion
      between severe and disabling muscle symptoms affecting the lower limbs
      attributable to an HMG CoA reductase inhibitor with and without ezetimbe and
      symptoms of neurogenic claudication due to spinal stenosis. The statins were not
      discontinued promptly leading to prolonged morbidity. Serum creatine kinase
      levels (CK) were normal in two patients and not recorded for the third.
      CONCLUSION: The reports include two safety issues, firstly the need to consider
      HMG CoA reductase inhibitors as a cause of severe lower limb muscle symptoms even
      in the presence of spinal stenosis and normal CK levels and the second, the need
      to measure serum creatine kinase when these symptoms occur to detect progression
      of myopathy and potentially serious outcomes.

PMID- 23135337
TI  - The paroxetine 352 bipolar trial: A study in medical ghostwriting.
AB  - BACKGROUND: The problem of ghostwriting in corporate-sponsored clinical trials is
      of concern to medicine, bioethics, and government agencies. We present a study of
      the ghostwritten archival report of an industry-sponsored trial comparing
      antidepressant treatments for bipolar depression: GlaxoSmithKline (GSK)
      paroxetine study 352. This analysis is based upon publicly available evidence
      presented in a complaint of research misconduct filed with the Office of Research
      Integrity of the Department of Health and Human Services. OBJECTIVES: We
      performed a deconstruction of the published study to show how primary and
      secondary outcome analyses were conflated, turning a 'negative' clinical trial
      into a 'positive' study - with conclusions and recommendations that could
      adversely affect patient health. METHODS: The paroxetine 352 study was a
      randomized, double-blind, placebo-controlled, 19-site trial comparing paroxetine
      and imipramine in 117 patients with bipolar type I major depressive episode which
      was unresponsive to prior lithium carbonate therapy. RESULTS: Analysis of the
      primary outcome measures found no statistically significant difference between
      paroxetine or imipramine versus placebo. However, the published article concluded
      that both drugs were efficacious versus placebo for a post hoc subgroup of
      patients. CONCLUSIONS: Few industry-sponsored studies gain public scrutiny. It is
      important to make these articles transparent to the scientific and medical
      community.

PMID- 23135338
TI  - Sponsorship bias in clinical research.
AB  - BACKGROUND: Pharmaceutical companies fund the vast majority of the clinical
      research that is undertaken on medications but face a conflict of interest
      between producing good science and results that will enhance the sales of their
      products. OBJECTIVES: To document concrete examples of bias in clinical research
      induced by pharmaceutical industry sponsorship. METHODS: This paper uses a
      thematic approach to documenting the extent of these biases in the following
      areas: research question/topic, choice of doses and comparator agents, control
      over trial design and changes in protocols, early termination of clinical trials,
      reporting to regulatory authorities, reinterpretation of data, restrictions on
      publication rights, use of fake journals, journal supplements and symposia,
      ghostwriting, publication and reporting of results and outcomes. RESULTS: Bias in
      favour of industry is apparent in every one of the themes examined with the
      result that research funded by industry undermines confidence in medical
      knowledge. CONCLUSIONS: Bias induced by commercial concerns can be countered in
      one of two ways. The first is to erect a firewall between the money and the
      people doing the research and the data analysis. The other approach is to develop
      an entirely separate funding source that is independent of the pharmaceutical
      industry.

PMID- 23135340
TI  - A disulfide-linked conjugate of ferrocenyl chalcone and silicon(IV)
      phthalocyanine as an activatable photosensitiser.
AB  - A novel bis(ferrocenyl chalcone) silicon(IV) phthalocyanine has been prepared in
      which the disulfide linker can be cleaved by dithiothreitol. The separation of
      the ferrocenyl quencher and the phthalocyanine core greatly enhances the
      fluorescence emission, singlet oxygen production and in vitro photocytotoxicity.

PMID- 23135341
TI  - Conceptual framework for health-related quality of life assessment in acute
      gastroenteritis.
AB  - BACKGROUND AND OBJECTIVES: To date, most trials in pediatric acute
      gastroenteritis have evaluated short-term clinical disease activity (eg, duration
      of diarrhea or vomiting, level of dehydration), laboratory outcomes (eg,
      rotavirus, norovirus), or a composite of these outcomes. Measuring health-related
      quality of life may also be important in evaluating the effect of interventions
      for acute gastroenteritis in children. The objectives of this study were to
      conduct individual interviews and, when possible, focus group discussions, with
      parents of children with acute gastroenteritis; to determine how parent and child
      quality of life is negatively affected by acute gastroenteritis; and, from the
      perspective of parents and children, to develop a conceptual framework for
      quality of life instrument specific to pediatric acute gastroenteritis. METHODS:
      We conducted interviews and focus groups with parents of children (3 months-5
      years of age) given a diagnosis of gastroenteritis in a hospital emergency
      department. Interviews and focus groups were conducted to determine the effect of
      gastroenteritis on quality of life in parents and children (as perceived by the
      parents). RESULTS: Interviews and focus groups involving 25 parents suggested a
      conceptual framework that, for children, includes 2 domains (physical and
      emotional function) and 14 subdomains. For parents, our framework includes 3
      domains (physical, emotional, and social function) with physical function
      including 4 subdomains, emotional function including 7 subdomains, and social
      function including 2 subdomains. The framework has been used to develop a
      preliminary quality of life questionnaire for parents and children. CONCLUSIONS:
      Acute gastroenteritis has an important adverse effect on health-related quality
      in both children and parents involving physical symptoms and restrictions in
      physical function and disturbed emotional function. Upon further research on the
      psychometric properties of the proposed questionnaires, future trials of
      effectiveness should consider measuring patient important outcomes such as health
      related quality of life.

PMID- 23135342
TI  - The pnicogen bond: its relation to hydrogen, halogen, and other noncovalent
      bonds.
AB  - Among a wide range of noncovalent interactions, hydrogen (H) bonds are well known
      for their specific roles in various chemical and biological phenomena. When
      describing conventional hydrogen bonding, researchers use the notation AH...D
      (where A refers to the electron acceptor and D to the donor). However, the AH
      molecule engaged in a AH...D H-bond can also be pivoted around by roughly 180
      degrees , resulting in a HA...D arrangement. Even without the H atom in a
      bridging position, this arrangement can be attractive, as explained in this
      Account. The electron density donated by D transfers into a AH sigma* antibonding
      orbital in either case: the lobe of the sigma* orbital near the H atom in the H
      bonding AH...D geometry, or the lobe proximate to the A atom in the HA...D case.
      A favorable electrostatic interaction energy between the two molecules
      supplements this charge transfer. When A belongs to the pnictide family of
      elements, which include phosphorus, arsenic, antimony, and bismuth, this type of
      interaction is called a pnicogen bond. This bonding interaction is somewhat
      analogous to the chalcogen and halogen bonds that arise when A is an element in
      group 16 or 17, respectively, of the periodic table.  Electronegative
      substitutions, such as a F for a H atom opposite the electron donor atom,
      strengthen the pnicogen bond. For example, the binding energy in FH(2)P...NH(3)
      greatly exceeds that of the paradigmatic H-bonding water dimer. Surprisingly, di-
      or tri-halogenation does not produce any additional stabilization, in marked
      contrast to H-bonds. Chalcogen and halogen bonds show similar strength to the
      pnicogen bond for a given electron-withdrawing substituent. This insensitivity to
      the electron-acceptor atom distinguishes these interactions from H-bonds, in
      which energy depends strongly upon the identity of the proton-donor atom.  As
      with H-bonds, pnicogen bonds can extract electron density from the lone pairs of
      atoms on the partner molecule, such as N, O, and S. The pi systems of carbon
      chains can donate electron density in pnicogen bonds. Indeed, the strength of
      A...pi pnicogen bonds exceeds that of H-bonds even when using strong proton
      donors such as water with the same pi system.  H-bonds typically have a high
      propensity for a linear AH...D arrangement, but pnicogen bonds show an even
      greater degree of anisotropy. Distortions of pnicogen bonds away from their
      preferred geometry cause a more rapid loss of stability than in H-bonds. Although
      often observed in dimers in the gas phase, pnicogen bonds also serve as the glue
      in larger aggregates, and researchers have found them in a number of diffraction
      studies of crystals.

PMID- 23135343
TI  - Safety, efficacy and convenience of colistimethate sodium dry powder for
      inhalation (Colobreathe DPI) in patients with cystic fibrosis: a randomised
      study.
AB  - PURPOSE: To assess efficacy and safety of a new dry powder formulation of inhaled
      colistimethate sodium in patients with cystic fibrosis (CF) aged >=6 years with
      chronic Pseudomonas aeruginosa lung infection. STUDY DESIGN AND METHODS: A
      prospective, centrally randomised, phase III, open-label study in patients with
      stable CF aged >=6 years with chronic P aeruginosa lung infection. Patients were
      randomised to Colobreathe dry powder for inhalation (CDPI, one capsule containing
      colistimethate sodium 1 662 500 IU, twice daily) or three 28-day cycles with
      twice-daily 300 mg/5 ml tobramycin inhaler solution (TIS). Study duration was 24
      weeks. RESULTS: 380 patients were randomised. After logarithmic transformation of
      data due to a non-normal distribution, adjusted mean difference between treatment
      groups (CDPI vs TIS) in change in forced expiratory volume in 1 s (FEV1%
      predicted) at week 24 was -0.98% (95% CI -2.74% to 0.86%) in the intention-to
      treat population (n=373) and -0.56% (95% CI -2.71% to 1.70%) in the per protocol
      population (n=261). The proportion of colistin-resistant isolates in both groups
      was <=1.1%. The number of adverse events was similar in both groups.
      Significantly more patients receiving CDPI rated their device as 'very easy or
      easy to use' (90.7% vs 53.9% respectively; p<0.001). CONCLUSION: CDPI
      demonstrated efficacy by virtue of non-inferiority to TIS in lung function after
      24 weeks of treatment. There was no emergence of resistance of P aeruginosa to
      colistin. Overall, CDPI was well tolerated. TRIAL REG NO: EudraCT 2004-003675-36.

PMID- 23135344
TI  - CASA derived human sperm abnormalities: correlation with chromatin packing and
      DNA fragmentation.
AB  - PURPOSE: The present study was undertaken to evaluate the effects of
      morphokinetic abnormalities of human spermatozoa on chromatin packing and DNA
      integrity and possible beneficial effects of sperm selection in ICSI. METHODS:
      Semen samples from 1002 patients were analysed for morphology and motility using
      CASA. Protamine status and DNA fragmentation were analysed by chromomycin A3
      staining and sperm chromatin dispersion assay respectively. RESULTS: Sperms with
      elongated, thin, round, pyri, amorphous, micro and macro forms were significantly
      higher in teratozoospermic and oligoasthenoteratozoospermic groups. Significant
      difference in chromatin packing and DNA fragmentation index was observed in these
      abnormal groups compared with normal. Similarly significant correlation was also
      seen between abnormal motility parameters and DNA fragmentation index in
      asthenozoospermic group compared with normal. CONCLUSIONS: Specific abnormal
      morphological forms have higher incidence of chromatin packing abnormalities and
      DNA fragmentation. Using these sperms in ICSI might have an impact on
      fertilization, embryo development and abortion rates. These can be selectively
      avoided during ICSI procedure to improve ART outcome.

PMID- 23135345
TI  - Assessing the effect of baseline status of serum bone turnover markers and
      vitamin D levels on efficacy of teriparatide 20 MUg/day administered
      subcutaneously in Japanese patients with osteoporosis.
AB  - In this previously reported multicenter study, teriparatide 20 MUg/day was
      administered to elderly Japanese subjects (93 % female; median age 70 years) with
      osteoporosis and at high risk of fracture during a 12-month, randomized, double
      blind, placebo-controlled period, which was followed by a 12 month treatment
      period in which all subjects received open-label teriparatide. Subjects were
      randomized 2:1 to teriparatide versus placebo (teriparatide n = 137, placebo
      teriparatide n = 70). This was an exploratory analysis to determine whether the
      baseline status of serum bone turnover markers (BTMs) and vitamin D levels affect
      the efficacy of teriparatide at 20 MUg/day. The BTMs included were type I
      procollagen N-terminal pro-peptide (P1NP) and type I collagen cross-linked C
      telopeptide (CTX). Changes in BMD were analyzed by subgroups: (1) tertile
      subgroups of BTM; (2) BTM determined by the upper limit of normal; and (3) level
      of vitamin D. Teriparatide increased lumbar spine BMD in all subgroups by 10 % or
      more through 24 months. Subgroups with higher baseline BTM levels had greater
      mean percent changes of lumbar spine BMD through 24 months. The baseline status
      of vitamin D sufficiency did not impact the mean percent change of lumbar spine
      BMD through 24 months. Results of this study suggest that clinically significant
      increases in BMD can be achieved in patients receiving teriparatide regardless of
      baseline BTM or vitamin D levels. Additionally, when vitamin D is coadministered,
      vitamin D insufficiency would not be expected to affect the overall efficacy of
      teriparatide.

PMID- 23135346
TI  - An efficient organocatalytic enantioselective synthesis of
      spironitrocyclopropanes.
AB  - An organocatalytic asymmetric synthesis of spironitrocyclopropanes has been
      demonstrated starting from 2-arylidene-1,3-indandiones and bromonitroalkanes
      catalyzed by a cinchona-derived bifunctional organocatalyst. The products were
      obtained with excellent enantioselectivities, diastereoselectivities and with
      good yields.

PMID- 23135347
TI  - Clinical application of UF-1000i in combination with AX-4280 for the screening
      test ability of urinary formed elements.
AB  - AIMS: To evaluate the screening test ability of UF-1000i combination with AX-4280
      for major pathological urinary formed elements and to establish screening rules
      suitable for our laboratory. METHODS: A total of 2220 cases of urine samples were
      collected from out-patients and inpatients. The sample tests were finished within
      4 h after collection. The results were verified and corroborated with microscopic
      tests. RESULTS: In 'both-negative' group, the negative predictive values for red
      blood cell, white blood cell and cast were 99.12%, 99.56% and 100%, respectively,
      and the false negative rates were 0.87%, 0.44% and 0%, respectively. In 'both
      positive' group, the positive predictive values for red blood cell, white blood
      cell and cast were 69.18%, 74.41% and 33.33%, respectively, and the false
      positive rates were 30.82%, 25.59% and 66.67%, respectively. In 'U positive/A
      negative' group, the positive predictive values for red blood cell, white blood
      cell and cast were 32.47%, 23.67% and 8.57%, respectively, and the false positive
      rates were 67.53%, 76.36% and 91.43%, respectively. In 'U negative/A positive'
      group, the positive predictive values for red blood cell, white blood cell and
      cast were 8.18%, 19.50% and 4.67%, respectively, and the false positive rates
      were 91.82%, 50.50% and 95.24%, respectively. CONCLUSIONS: When the results of
      the red blood cell, white blood cell and cast tested by UF-1000i were all
      negative, and the results of the red blood cell, white blood cell and protein
      tested by AX-4280 were negative, an automatic report stating 'normal microscopic
      appearance' was generated, and then the microscopic test rate was reduced by
      37.6%. However, if any automated parameter measurement was out of the reference
      range, corroboration by manual microscopy was advisable.

PMID- 23135348
TI  - Clinical consequences of erroneous laboratory results that went unnoticed for 10
      days.

PMID- 23135349
TI  - Genetic and epigenetic markers in the evaluation of pancreatic masses.
AB  - BACKGROUND: Methylation markers have shown promise in the early diagnosis of
      pancreatic carcinoma. The aim of this study was to assess the diagnostic utility
      of hypermethylation status of candidate genes in combination with KRAS mutation
      detection in the evaluation of pancreatic masses. EXPERIMENTAL DESIGN: Sixty-one
      fine needle aspirates of pancreatic masses (43 pancreatic adenocarcinomas and 18
      chronic pancreatitis) were studied. Methylation status of HRH2, EN1, SPARC, CDH13
      and APC were analysed using melting curve analysis after DNA bisulfite treatment.
      KRAS mutations were also analysed. RESULTS: The methylation panel had a
      sensitivity of 73% (27 of 37, CI 95% 56 to 86%) and a specificity of 100%
      whenever two or more promoters were found hypermethylated. KRAS mutations showed
      a sensitivity of 77% (33 of 43, CI 95% 62 to 88%) and a specificity of 100%. Both
      molecular analyses added useful information to cytology by increasing the number
      of informative cases. When genetic and epigenetic analyses were combined
      sensitivity was 84% (36 of 43 CI 95% 69 to 93%) maintaining a 100% specificity.
      CONCLUSIONS: Analysis of hypermethylation status of a panel of genes and KRAS
      mutation detection offer a similar diagnostic yield in the evaluation of
      pancreatic masses. The combined molecular analysis increases the number of
      informative cases without diminishing specificity.

PMID- 23135350
TI  - Obese patients may have more soft tissue impingement following primary total hip
      arthroplasty.
AB  - PURPOSE: Several studies have reported a risk of dislocation in obese patients
      after total hip arthroplasty. In this study, we evaluated the interaction between
      obesity and dislocation by kinematic analysis using a navigation system. METHODS:
      The intraoperative range of motion (ROM) and postoperative impingement-free ROM
      were measured in 38 patients, and we compared the impingement-free ROM in obese
      and non obese patients. RESULTS: The postoperatively simulated ROM was similar in
      the obese and non obese groups. The intraoperative ROM was smaller in the obese
      group. The difference values between the intraoperative ROM and postoperatively
      simulated ROM were larger in the obese group. These results indicate that obese
      patients have less ROM following primary total hip arthroplasty even when the
      implant positioning is performed correctly. CONCLUSIONS: Dislocations are
      multifactorial problems including soft tissue impingement. Therefore, the risk of
      dislocation caused by soft tissue impingement in obese patients may be increased.

PMID- 23135351
TI  - Diagnosis of influenza from lower respiratory tract sampling after negative upper
      respiratory tract sampling.
AB  - In this retrospective cohort study, we demonstrate that PCR-confirmed diagnoses
      of influenza were made solely by lower respiratory sampling in 6.9% of cases, as
      traditional upper respiratory tract tests were negative, indeterminate or not
      performed. Clinical features of these cases are presented. Clinicians should
      consider lower respiratory tract sampling in select cases of influenza-like
      illness for diagnosis.

PMID- 23135352
TI  - Epigenetics-related genes in prostate cancer: expression profile in prostate
      cancer tissues, androgen-sensitive and -insensitive cell lines.
AB  - Epigenetic changes have been suggested to drive prostate cancer (PCa) development
      and progression. Therefore, in this study, we aimed to identify novel epigenetics
      related genes in PCa tissues, and to examine their expression in metastatic PCa
      cell lines. We analyzed the expression of epigenetics-related genes via a
      clustering analysis based on gene function in moderately and poorly
      differentiated PCa glands compared to normal glands of the peripheral zone
      (prostate proper) from PCa patients using Whole Human Genome Oligo Microarrays.
      Our analysis identified 12 epigenetics-related genes with a more than 2-fold
      increase or decrease in expression and a p-value <0.01. In modera-tely
      differentiated tumors compared to normal glands of the peripheral zone, we found
      the genes, TDRD1, IGF2, DICER1, ADARB1, HILS1, GLMN and TRIM27, to be
      upregulated, whereas TNRC6A and DGCR8 were found to be downregulated. In poorly
      differentiated tumors, we found TDRD1, ADARB and RBM3 to be upregulated, whereas
      DGCR8, PIWIL2 and BC069781 were downregulated. Our analysis of the expression
      level for each gene in the metastatic androgen-sensitive VCaP and LNCaP, and 
      insensitive PC3 and DU-145 PCa cell lines revealed differences in expression
      among the cell lines which may reflect the different biological properties of
      each cell line, and the potential role of each gene at different metastatic
      sites. The novel epigenetics-related genes that we identified in primary PCa
      tissues may provide further insight into the role that epigenetic changes play in
      PCa. Moreover, some of the genes that we identified may play important roles in
      primary PCa and metastasis, in primary PCa only, or in metastasis only. Follow-up
      studies are required to investigate the functional role and the role that the
      expression of these genes play in the outcome and progression of PCa using tissue
      microarrays.

PMID- 23135353
TI  - Prognostic significance of 11q23 aberrations in adult acute myeloid leukemia and
      the role of allogeneic stem cell transplantation.
AB  - The clinical features and outcomes of 148 patients with acute myeloid leukemia
      (AML) and 11q23 chromosomal abnormalities were compared with those of 2640
      patients with non-11q23 AML. Patients with t(9;11) ), t(6;11) or other 11q23
      balanced translocations (t(11;v)(q23;v)) presented at a younger age and with
      higher percentage of bone marrow blasts. Unbalanced 11q23 abnormalities were
      commonly associated with deletions of chromosomes 5q, 7q and/or complex
      karyotypes. In multivariate analysis, when compared with patients with non-11q23
      AML and unfavorable-risk karyotype, there was a significant difference in overall
      survival (OS) for patients with t(9;11) (P=0.004), whereas there were no
      differences in OS for patients with t(6;11) (P=0.62), t(11;19) (P=0.20) and
      unbalanced 11q23 aberrations (P=0.85) or t(11;v)(q23;v) (P=0.59), indicating that
      t(9;11) has an independent intermediate prognostic significance, with all others
      being poor prognostic factors for OS; this was further confirmed by comparing
      them with patients with non-11q23 AML and intermediate-risk karyotype. Using
      intention-to treat analysis based on donor availability, we also noted that
      allogeneic stem cell transplant in first remission had a significant benefit
      toward improving OS (P<0.001) and relapse-free survival (P<0.001) in patients
      with AML and 11q23 abnormalities.

PMID- 23135354
TI  - Mutations of the epigenetics-modifying gene (DNMT3a, TET2, IDH1/2) at diagnosis
      may induce FLT3-ITD at relapse in de novo acute myeloid leukemia.
AB  - Gene mutations were found in acute myeloid leukemia (AML) and their importance
      has been noted. To clarify the importance and stability of mutations, we examined
      gene mutations in paired samples at diagnosis and relapse of 34 adult AML
      patients. Five acquired gene mutations were detected at relapse. Of the 45 gene
      mutations at diagnosis, 11 of them were lost at relapse. The acquired mutations
      at relapse were all class I mutations as Fms-like tyrosine kinase 3 (FLT3) and
      rat sarcoma viral oncogene homolog (RAS) mutations. The disappeared mutations at
      relapse were 3 of 11 internal tandem duplications of FLT3 (FLT3-ITD) (27.3%), 3
      of 3 FLT3 tyrosine kinase domain (FLT3-TKD) (100%), 3 of 13 Nucleophosmin 1
      (23.1%) and 2 of 5 CCAAT/enhancer-binding protein-alpha (40%) mutations. However,
      epigenetics-modifying gene (DNMT3a, TET2 and IDH1/2) mutations had no change
      between diagnosis and relapse samples, and may become minimal residual disease
      marker. The frequency of FLT3-ITD at relapse in patients with DNMT3a mutation at
      diagnosis is significantly higher than those in patients without them (P=0.001).
      Moreover, the high frequency of FLT3-ITD at relapse is also seen in AML cases
      that initially present with any epigenetics-modifying gene mutations (P<0.001).
      Our results indicate that epigenetics-modifying gene mutations may cause genetic
      instability and induce FLT3-ITD, leading to resistance to therapy and relapse.

PMID- 23135355
TI  - Parental imprinting regulates insulin-like growth factor signaling: a Rosetta
      Stone for understanding the biology of pluripotent stem cells, aging and
      cancerogenesis.
AB  - In recent years, solid evidence has accumulated that insulin-like growth factor-1
      (IGF-1) and 2 (IGF-2) regulate many biological processes in normal and malignant
      cells. Recently, more light has been shed on the epigenetic mechanisms regulating
      expression of genes involved in IGF signaling (IFS) and it has become evident
      that these mechanisms are crucial for initiation of embryogenesis, maintaining
      the quiescence of pluripotent stem cells deposited in adult tissues (for example,
      very-small embryonic-like stem cells), the aging process, and the malignant
      transformation of cells. The expression of several genes involved in IFS is
      regulated at the epigenetic level by imprinting/methylation within differentially
      methylated regions (DMRs), which regulate their expression from paternal or
      maternal chromosomes. The most important role in the regulation of IFS gene
      expression is played by the Igf-2-H19 locus, which encodes the
      autocrine/paracrine mitogen IGF-2 and the H19 gene, which gives rise to a non
      coding RNA precursor of several microRNAs that negatively affect cell
      proliferation. Among these, miR-675 has recently been demonstrated to
      downregulate expression of the IGF-1 receptor. The proper imprinting of DMRs at
      the Igf-2-H19 locus, with methylation of the paternal chromosome and a lack of
      methylation on the maternal chromosome, regulates expression of these genes so
      that Igf-2 is transcribed only from the paternal chromosome and H19 (including
      miR-675) only from the maternal chromosome. In this review, we will discuss the
      relevance of (i) proper somatic imprinting, (ii) erasure of imprinting and (iii)
      loss of imprinting within the DMRs at the Igf-2-H19 locus to the expression of
      genes involved in IFS, and the consequences of these alternative patterns of
      imprinting for stem cell biology.

PMID- 23135356
TI  - A response-adjusted PET-based transplantation strategy in primary resistant and
      relapsed Hodgkin Lymphoma.

PMID- 23135357
TI  - Diffusion tensor imaging reveals evolution of primate brain architectures.
AB  - Evolution of the brain has been an inherently interesting problem for centuries.
      Recent studies have indicated that neuroimaging is a powerful technique for
      studying brain evolution. In particular, a variety of reports have demonstrated
      that consistent white matter fiber connection patterns derived from diffusion
      tensor imaging (DTI) tractography reveal common brain architecture and are
      predictive of brain functions. In this paper, based on our recently discovered
      358 dense individualized and common connectivity-based cortical landmarks
      (DICCCOL) defined by consistent fiber connection patterns in DTI datasets of
      human brains, we derived 65 DICCCOLs that are common in macaque monkey,
      chimpanzee and human brains and 175 DICCCOLs that exhibit significant
      discrepancies amongst these three primate species. Qualitative and quantitative
      evaluations not only demonstrated the consistencies of anatomical locations and
      structural fiber connection patterns of these 65 common DICCCOLs across three
      primates, suggesting an evolutionarily preserved common brain architecture but
      also revealed regional patterns of evolutionarily induced complexity and
      variability of those 175 discrepant DICCCOLs across the three species. 

PMID- 23135358
TI  - Shape and curvedness analysis of brain morphology using human fetal magnetic
      resonance images in utero.
AB  - The 3-D morphological change has gained increasing significance in recent
      investigations on human fetal brains. This study uses a pair of new indices, the
      shape index (SI) and curvedness index (CVD), to quantify 3-D morphological
      changes in developing brains from 22 to 33 weeks of gestation. The SI was used to
      automatically locate the gyral nodes and sulcal pits, and the CVD was used to
      measure the degree of deviation of cortical shapes from a flat plane. The CVD
      values of classified regions were compared with two traditional biomarkers:
      cerebral volume and cortical surface area. Because the fetal brains dramatically
      deform with age, the age effect was controlled during the comparison between
      morphological changes and volume and surface area. The results show that cerebral
      volume, the cortical surface area, and the CVD values of gyral nodes and sulcal
      pits increased with gestational age. However, with age controlled, the CVD values
      of gyral nodes and sulcal pits did not correlate with cerebral volume, but the
      CVD of gyral nodes increased slightly with the cortical surface area. These
      findings suggest that the SI, in conjunction with the CVD, provides developmental
      information distinct from the brain volumetry. This approach provides additional
      insight into 3-D cortical morphology in the assessment of fetal brain
      development.

PMID- 23135359
TI  - Endocrine gland-derived vascular endothelial growth factor strengthens cell
      invasion ability via prokineticin receptor 2 in colon cancer cell lines.
AB  - Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) has recently
      been identified as one of the vascular endothelial growth factors, and it is
      considered that the overexpression of EG-VEGF in colon cancer is related to
      hepatic metastasis. In this study, we report our recent novel findings of the
      involvement of EG-VEGF in cell invasion of colon cancer cells. Colon cancer cell
      lines (DLD-1 and HCT116) with high expression of prokineticin receptor (PK-R) 1
      and 2 were stimulated with the EG-VEGF protein. Furthermore, Matrigel cell
      invasion assay was performed to examine the changes in cancer cell invasion. In
      addition, we investigated the mRNA expression of matrix metalloproteinase (MMP)
      2, -7 and -9 in cancer cells. Finally, the EG-VEGF receptor on the colon cancer
      cell membrane was blocked by anti-PK-R1 and -PK-R2 antibodies to study whether
      cell invasion ability would be altered. In colon cancer cell lines where the
      expression of PK-R1 and 2 was confirmed, stimulation with EG-VEGF increased cell
      invasion a maximum of ~3-5 times. Furthermore, an increase in the mRNA and
      protein expression of MMP-2, -7 and -9 was observed. We also observed that the
      cell invasion rate decreased only after exposure to the anti-PK-R2 antibody. The
      study showed that the EG-VEGF protein may act on MMP-2, -7 and -9 via PK-R2 to
      strengthen cell invasion ability in colon cancer cell lines.

PMID- 23135360
TI  - "Click" polymerization on a self-assembled monolayer: a convenient approach to
      functionalize various surfaces with polytriazoles.
AB  - "Click" polymerization reaction has been performed on the functional self
      assembled monolayer to incorporate polytriazoles. Ellipsometric and atomic force
      microscopic studies indicated a high degree of polymerization and fairly dense
      surface coverage. Band gap calculation revealed the possibility of its use as a
      semiconducting material.

PMID- 23135361
TI  - New mite invasions in citrus in the early years of the 21st century.
AB  - Several mite species commonly attack cultivated citrus around the world. Up to
      104 phytophagous species have been reported causing damage to leaves, buds and
      fruits, but only a dozen can be considered major pests requiring control
      measures. In recent years, several species have expanded their geographical range
      primarily due to the great increase in trade and travel worldwide, representing a
      threat to agriculture in many countries. Three spider mite species (Acari:
      Tetranychidae) have recently invaded the citrus-growing areas in the
      Mediterranean region and Latin America. The Oriental red mite, Eutetranychus
      orientalis (Klein), presumably from the Near East, was detected in southern Spain
      in 2001. The Texas citrus mite, Eutetranychus banksi (McGregor), is widely
      distributed in North, Central and South America. It was first reported in Europe
      in 1999 on citrus in Portugal; afterwards the mite invaded the citrus orchards in
      southern Spain. In Latin America, the Hindustan citrus mite, Schizotetranychus
      hindustanicus (Hirst), previously known only from citrus and other host plants in
      India, was reported causing significant damage to citrus leaves and fruits in
      Zulia, northwest Venezuela, in the late 1990s. Later, this mite species spread to
      the southeast being detected on lemon trees in the state of Roraima in northern
      Brazil in 2008. Whereas damage levels, population dynamics and control measures
      are relatively well know in the case of Oriental red mite and Texas citrus mite,
      our knowledge of S. hindustanicus is noticeably scant. In the present paper,
      information on pest status, seasonal trends and natural enemies in invaded areas
      is provided for these species, together with morphological data useful for
      identification. Because invasive species may evolve during the invasion process,
      comparison of behavior, damage and management options between native and invaded
      areas for these species will be useful for understanding the invader's success
      and their ability to colonize new regions.

PMID- 23135362
TI  - High-resolution molecular imaging via intravital microscopy: illuminating
      vascular biology in vivo.
AB  - Complications of atherosclerosis and thrombosis are leading causes of death
      worldwide. While experimental investigations have yielded valuable insights into
      key molecular and cellular phenomena in these diseases of medium- and large-sized
      vessels, direct visualization of relevant in vivo biological processes has been
      limited. However, recent developments in molecular imaging technology,
      specifically fluorescence imaging agents coupled with high-resolution, high-speed
      intravital microscopy (IVM), are now enabling dynamic and longitudinal
      investigations into the mechanisms and progression of many vascular diseases.
      Here we review recent advances in IVM that have provided new in vivo biological
      insights into atherosclerosis and thrombosis.

PMID- 23135363
TI  - Head impact exposure sustained by football players on days of diagnosed
      concussion.
AB  - PURPOSE: This study compares the frequency and severity of head impacts sustained
      by football players on days with and without diagnosed concussion and to identify
      the sensitivity and specificity of single-impact severity measures to diagnosed
      injury. METHODS: One thousand two hundred eight players from eight collegiate
      football teams and six high school football teams wore instrumented helmets to
      measure head impacts during all team sessions, of which 95 players were diagnosed
      with concussion. Eight players sustained two injuries and one sustained three,
      providing 105 injury cases. Measures of head kinematics (peak linear and
      rotational acceleration, Gadd severity index, head injury criteria (HIC15), and
      change in head velocity (Deltav)) and the number of head impacts sustained by
      individual players were compared between days with and without diagnosed
      concussion. Receiver operating characteristic curves were generated to evaluate
      the sensitivity and specificity of each kinematic measure to diagnosed concussion
      using only those impacts that directly preceded diagnosis. RESULTS: Players
      sustained a higher frequency of impacts and impacts with more severe kinematic
      properties on days of diagnosed concussion than on days without diagnosed
      concussion. Forty-five injury cases were immediately diagnosed after head impact.
      For these cases, peak linear acceleration and HIC15 were most sensitive to
      immediately diagnosed concussion (area under the curve = 0.983). Peak rotational
      acceleration was less sensitive to diagnosed injury than all other kinematic
      measures (P = 0.01), which are derived from linear acceleration (peak linear,
      HIC15, Gadd severity index, and Deltav). CONCLUSIONS: Players sustained more
      impacts and impacts of higher severity on days of diagnosed concussion than on
      days without diagnosed concussion. In addition, of historical measures of impact
      severity, those associated with peak linear acceleration are the best predictors
      of immediately diagnosed concussion.

PMID- 23135365
TI  - Adiposity, aerobic fitness, muscle fitness, and markers of inflammation in
      children.
AB  - PURPOSE: The purpose of this study was to describe levels of inflammation markers
      in Norwegian children and to examine the associations of adiposity, aerobic
      fitness, and muscle fitness with markers of inflammation. METHODS: In 2005-2006,
      1467 nine-year-olds were randomly selected from all regions in Norway. The
      participation rate was 89%. The inflammatory markers evaluated included C
      reactive protein (CRP), leptin, adiponectin, plasminogen activator inhibitor-1,
      tumor necrosis factor-alpha, hepatocyte growth factor, resistin, and interleukin
      6. We assessed muscular strength by measuring explosive, isometric, and endurance
      strength. Aerobic fitness was measured directly during a maximal cycle ergometer
      test. Adiposity was expressed as waist circumference (WC). RESULTS: The girls had
      significantly higher levels of CRP, leptin, adiponectin, and resistin and lower
      levels of tumor necrosis factor-alpha compared with the boys. We observed a
      graded association of CRP and leptin levels across quintiles of WC, aerobic
      fitness, and muscle fitness (P <= 0.001 for all participants). The regression
      analyses revealed that WC, aerobic fitness, and muscle fitness were independently
      associated with the CRP (WC beta = 0.158, P < 0.001; aerobic fitness beta = 
      0.190, P < 0.001; muscle fitness beta = -0.122, P < 0.002) after adjustments for
      sex, age, Tanner pubertal stage, and the other independent variables. The same
      pattern was observed for leptin levels (WC beta = 0.406, P < 0.001; aerobic
      fitness beta = -0.298, P < 0.001; muscle fitness beta = -0.064, P < 0.036).
      CONCLUSIONS: These data represent a reference material with respect to
      inflammatory markers. Our results show that adiposity, aerobic fitness, and
      muscle fitness were independently associated with the CRP and leptin levels.

PMID- 23135364
TI  - Timing of concussion diagnosis is related to head impact exposure prior to
      injury.
AB  - PURPOSE: Concussions are commonly undiagnosed in an athletic environment because
      the postinjury signs and symptoms may be mild, masked by the subject, or
      unrecognized. This study compares measures of head impact frequency, location,
      and kinematic response before cases of immediate and delayed concussion
      diagnosis. METHODS: Football players from eight collegiate and six high school
      teams wore instrumented helmets during play (n = 1208), of which 95 were
      diagnosed with concussion (105 total cases). Acceleration data recorded by the
      instrumented helmets were reduced to five kinematic metrics: peak linear and
      rotational acceleration, Gadd severity index, head injury criterion, and change
      in head velocity (Deltav). In addition, each impact was assigned to one of four
      general location regions (front, back, side, and top), and the number of impacts
      sustained before injury was calculated over two periods (1 and 7 days). RESULTS:
      All head kinematic measures associated with injury, except peak rotational
      acceleration (P = 0.284), were significantly higher for cases of immediate
      diagnosis than delayed diagnosis (P < 0.05). Players with delayed diagnosis
      sustained a significantly higher number of head impacts on the day of injury
      (32.9 +/- 24.9, P < 0.001) and within 7 d of injury (69.7 +/- 43.3, P = 0.006)
      than players with immediate diagnosis (16.5 +/- 15.1 and 50.2 +/- 43.6). Impacts
      associated with concussion occurred most frequently to the front of the head
      (46%) followed by the top (25%), side (16%), and back (13%) with the number of
      impacts by location independent of temporal diagnosis (chi(3) = 4.72, P = 0.19).
      CONCLUSIONS: Concussions diagnosed immediately after an impact event are
      associated with the highest kinematic measures, whereas those characterized by
      delayed diagnosis are preceded by a higher number of impacts.

PMID- 23135366
TI  - Lumbo-pelvic biomechanics and quadratus lumborum asymmetry in cricket fast
      bowlers.
AB  - PURPOSE: This study aimed to analyze lumbo-pelvic lateral flexion kinematics and
      kinetics in junior fast bowlers and compare bowlers with varying quadratus
      lumborum (QL) cross-sectional area (CSA) asymmetry profiles. METHODS: Magnetic
      resonance imaging was used to determine QL CSA of 39 participants who also
      underwent three-dimensional analysis of their bowling action. RESULTS: Bowlers
      with greater than 10% QL asymmetry (n = 26) experienced a larger peak lumbo
      pelvic lateral flexion; angle (21.6 degrees  +/- 4.2 degrees ), angular velocity
      (314.9 degrees .s +/- 86.6 degrees .s), moment (12.8 +/- 2.5 N.m.kg.m), positive
      power (25.6 +/- 12.6 W.kg.m), and negative power (48.6 +/- 20.9 W.kg.m) compared
      with the bowlers with less than 10% asymmetry (n = 13) (angle = 18.1 degrees  +/-
      1.9 degrees , angular velocity = 243.8 degrees .s +/- 64.9 degrees .s, moment =
      10.4 +/- 2.8 N.m.kg.m, positive power = 14.7 +/- 7.4 W.kg.m, and negative power =
      33.8 +/- 17.7 W.kg.m; P < 0.05). CONCLUSION: Fast bowlers with QL CSA asymmetry
      in excess of 10% experience increased lumbo-pelvic lateral flexion loads during
      bowling. As increased lateral flexion loads may increase the risk of
      spondylolysis development, the presence of large QL asymmetry may be a useful
      screening tool for identifying bowlers at risk of developing lumbar
      spondylolysis.

PMID- 23135367
TI  - Caffeine decreases systemic urea in elite soccer players during intermittent
      exercise.
AB  - PURPOSE: We investigated the effects of caffeine on the ammonia and amino acid
      metabolism of elite soccer players. METHODS: In this double-blind randomized
      study, athletes (n = 19) received 5 mg.kg caffeine or lactose (LEx, control) and
      performed 45 min of intermittent exercise followed by an intermittent recovery
      test (Yo-Yo IR2) until exhaustion. The caffeine-supplemented athletes were
      divided into two groups (CEx and SCEx) depending on their serum caffeine levels
      (<900% and >10,000%, respectively). Data were analyzed by ANOVA and Tukey post
      hoc test (P < 0.05 was considered to be statistically significant). RESULTS:
      Caffeine supplementation did not significantly affect the performance (LEx = 12.3
      +/- 0.3 km.h, 1449 +/- 378 m; CEx = 12.2 +/- 0.5 km.h, 1540 +/- 630 m; SCEx =
      12.3 +/- 0.5 km.h, 1367 +/- 330 m). Exercise changed the blood concentrations of
      several amino acids and increased the serum concentrations of ammonia, glucose,
      lactate, and insulin. The LEx group showed an exercise-induced increase in valine
      (~29%), which was inhibited by caffeine. Higher serum caffeine levels abolished
      the exercise-induced increase (~24%-27%) in glutamine but did not affect the
      exercise-induced increase in alanine (~110%-160%) and glutamate (42%-61%). In
      response to exercise, the SCEx subjects did not exhibit an increase in uremia and
      showed a significantly lower increase in their serum arginine (15%), citrulline
      (16%), and ornithine (ND) concentrations. CONCLUSIONS: Our data suggest that
      caffeine might decrease systemic urea by decreasing the glutamine serum
      concentration, which decreases the transportation of ammonia to the liver and
      thus urea synthesis.

PMID- 23135368
TI  - Aspirin and clopidogrel alter core temperature and skin blood flow during heat
      stress.
AB  - Antithrombotic therapy with oral aspirin (ASA) or clopidogrel (CLO) (Plavix;
      Bristol-Myers Squibb, Bridgewater, NJ) is associated with an attenuated skin
      vasodilator response and a greater rate of rise in core temperature in healthy,
      middle-age individuals during passive heating in a water perfused suit. PURPOSE:
      The present double-blind, crossover study examined the functional consequences of
      7 d of low-dose ASA (81 mg.d) versus CLO (75 mg.d) treatment in 14 healthy,
      middle-age (50-65 yr) men and women during passive heating in air (40 min at 30
      degrees C, 40% relative humidity) followed by exercise (60% VO2peak). METHODS:
      Oral temperature (Tor) was measured in the antechamber (23.0 degrees C +/- 0.1
      degrees C) before entering a warm environmental chamber. After 40 min of rest,
      subjects cycled on a recumbent cycle ergometer for up to 120 min. Esophageal
      temperature (Tes) and laser Doppler flux were measured continuously, and the
      latter was normalized to maximal cutaneous vascular conductance (%CVCmax).
      RESULTS: Before entry into the environmental chamber there were no differences in
      Tor among treatments; however, after 40 min of rest in the heat, Tes was
      significantly higher for ASA and CLO versus placebo (37.2 degrees C +/- 0.1
      degrees C, 37.3 degrees C +/- 0.1 degrees C, vs 37.0 degrees C +/- 0.1 degrees C,
      both P < 0.001), a difference that persisted throughout exercise (P < 0.001 vs
      placebo). The mean body temperature thresholds for the onset of cutaneous
      vasodilation were shifted to the right for both ASA and CLO during exercise (P <
      0.05). CONCLUSION: ASA and CLO resulted in elevated core temperatures during
      passive heat stress and shifted the onset of peripheral thermoeffector mechanisms
      toward higher body temperatures during exercise heat stress.

PMID- 23135369
TI  - Exercise-associated hyponatremia and hydration status in 161-km ultramarathoners.
AB  - PURPOSE: This work combines and reanalyzes 5 yr of exercise-associated
      hyponatremia (EAH) research at 161-km ultramarathons in northern California with
      primary purposes to define the relationship between postrace blood sodium
      concentration ([Na]) and change in body weight; to examine the interactions among
      EAH incidence, ambient temperature, and hydration state; and to explore the
      effect of hydration status on performance. METHODS: Prerace and postrace body
      weight and finish time data were obtained on 887 finishers, and postrace [Na] was
      also obtained on a subset of 669 finishers. RESULTS: EAH incidence was 15.1%
      overall (range, 4.6%-51.0% by year) and had a significant positive relationship
      with ambient temperature. Of the runners with EAH, 23.8% were classified as
      overhydrated (weight change, >=0), 40.6% were euhydrated (weight change, <0% to 
      3%), and 35.6% were dehydrated (weight change, <-3%) at the finish. There was a
      weak significant relationship (r = 0.17, P < 0.0001) between postrace [Na] and
      change in body weight such that a lower [Na] was more common with increased
      weight loss. Considering all finishers examined, 18.5% were dehydrated and 34.9%
      were overhydrated at the finish. There was a weak significant relationship (r =
      0.092, P = 0.006) between change in body weight and performance in that faster
      runners tended to lose more weight. Top finishers varied in body weight change
      from ~1% gain to ~6% loss. CONCLUSIONS: EAH incidence can be high in 161-km
      ultramarathons in northern California. In this environment, EAH is more common
      with dehydration than overhydration and is more common in hotter ambient
      temperature conditions. Because weight loss >3% does not seem to have an adverse
      effect on performance, excessive sodium supplementation and aggressive fluid
      ingestion beyond the dictates of thirst are ill advised.

PMID- 23135370
TI  - Subconcussive head impact biomechanics: comparing differing offensive schemes.
AB  - PURPOSE: Recent literature suggests that subconcussive impacts may influence
      cognitive functioning across the life span. These effects are suggested to
      manifest as functional and possibly structural changes. Head impact biomechanics
      during American football have been characterized from the high school to
      professional level, but style of play has not been considered. The aim of this
      investigation was to quantify and compare head impact frequencies and magnitudes
      between two different offensive schemes. METHODS: We investigated the frequencies
      and magnitudes (linear acceleration [g], rotational acceleration [rad.s], and
      HITsp) of head impacts sustained by 83 high school football athletes, playing for
      schools using two different offensive schemes. The two schemes comprised a run
      first offense (42 athletes) and a pass-first offense (41 athletes). The Head
      Impact Telemetry System was used to record head impact measures. RESULTS: A total
      of 35,620 impacts were recorded across two seasons. Athletes in the run-first
      offense sustained an average of 456 head impacts per season (41 practices and 9
      games), whereas the pass-first offense athletes sustained an average of 304 head
      impacts per season (44 practices and 9 games). The pass-first offense, however,
      sustained significantly higher impact magnitudes (P values < 0.05; 28.56g,
      1777.58 rad.s, and 16.24) than the run-first offense (25.67g, 1675.36 rad.s, and
      15.48) across a season. CONCLUSIONS: These data provide a first look at how
      different offensive strategies may influence head impact exposure in football
      athletes. In the study population, a run-first offense was associated with more
      frequent head impacts, of smaller magnitude, than a pass-first offense.

PMID- 23135371
TI  - The acute transverse strain response of the patellar tendon to quadriceps
      exercise.
AB  - INTRODUCTION: The human patellar tendon is highly adaptive to changes in habitual
      loading, but little is known about its acute mechanical response to exercise.
      This research evaluated the immediate transverse strain response of the patellar
      tendon to a bout of resistive quadriceps exercise. METHODS: Twelve healthy adult
      males (mean age, 34.0 +/- 12.1 yr; height, 1.75 +/- 0.09 m; and weight, 76.7 +/-
      12.3 kg) free of knee pain participated in the research. A 10- to 5-MHz linear
      array transducer was used to acquire standardized sagittal sonograms of the right
      patellar tendon immediately before and after 90 repetitions of a double-leg
      parallel-squat exercise performed against a resistance of 175% bodyweight. Tendon
      thickness was determined 20-mm distal to the pole of the patellar, and transverse
      Hencky strain was calculated as the natural log of the ratio of post- to
      preexercise tendon thickness and expressed as a percentage. Measures of tendon
      echotexture (echogenicity and entropy) were also calculated from subsequent
      grayscale profiles. RESULTS: Quadriceps exercise resulted in an immediate
      decrease in patellar tendon thickness (P < 0.05), equating to a transverse strain
      of -22.5% +/- 3.4% and was accompanied by increased tendon echogenicity (P <
      0.05) and decreased entropy (P < 0.05). The transverse strain response of the
      patellar tendon was significantly correlated with both tendon echogenicity (r = 
      0.58, P < 0.05) and entropy after exercise (r = 0.73, P < 0.05), whereas older
      age was associated with greater entropy of the patellar tendon before exercise (r
      = 0.79, P < 0.05) and a reduced transverse strain response (r = 0.61, P < 0.05)
      after exercise. CONCLUSIONS: This study is the first to show that quadriceps
      exercise invokes structural alignment and fluid movement within the matrix that
      are manifested by changes in echotexture and transverse strain in the patellar
      tendon.

PMID- 23135372
TI  - Effect of low recumbent angle on cycling performance, fatigue, and VO(2)
      kinetics.
AB  - PURPOSE: This study aimed to examine the effect of the degree of inclination from
      upright to supine postures on cycling performance, fatigue, and oxygen uptake
      (VO(2)) kinetics. METHODS: In experiment 1, 10 subjects performed graded and
      fatigue (exhaustive constant-load heavy exercise with 10 s all-out efforts
      interspersed every minute) tests at four cycling postures: upright, 30 degrees 
      recumbent (R), 15 degrees  R, and supine. In experiment 2, nine different
      subjects performed two bouts of constant-load heavy exercise in the same four
      cycling postures. Bout 1 was brought to failure, and bout 2 was limited to 6 min,
      so that the breath-by-breath VO(2) data from the first 6 min of each bout were
      averaged and curve fit. RESULTS: The time sustained during the graded test was
      significantly shorter in the supine compared with the other three postures and
      also shorter in the 15 degrees  R compared with the upright. The rate of fatigue
      was higher in the supine compared with the other three postures, and the
      normalized EMG activities of three leg muscles at end exercise were larger in the
      supine (and in some cases 15 degrees  R) compared with upright posture. The time
      sustained (min) during high-intensity constant-load cycling was significantly
      longer during upright (12.8 +/- 5.3) and 30 degrees  R (14.2 +/- 6.1) compared
      with 15 degrees  R (8.5 +/- 1.7) and supine (6.8 +/- 2.0) postures, but the
      amplitudes of the slow component of the VO(2) response (L.min) were larger during
      15 degrees  R (0.57 +/- 0.10) and supine (0.61 +/- 0.15) compared with 30 degrees
      R (0.39 +/- 0.12) and also larger in the supine than upright (0.43 +/- 0.13)
      postures. Inert gas rebreathing analysis revealed similar cardiac output
      responses at 60 s into the exercise among postures. CONCLUSION: Lowering the
      recumbent angle to 15 degrees  resulted in shorter performance, larger fatigue,
      and altered VO(2) kinetics.

PMID- 23135373
TI  - Predictive models of acute mountain sickness after rapid ascent to various
      altitudes.
AB  - PURPOSE: Despite decades of research, no predictive models of acute mountain
      sickness (AMS) exist, which identify the time course of AMS severity and
      prevalence following rapid ascent to various altitudes. METHODS: Using general
      linear and logistic mixed models and a comprehensive database, we analyzed 1292
      AMS cerebral factor scores in 308 unacclimatized men and women who spent between
      4 and 48 h at altitudes ranging from 1659 to 4501 m under experimentally
      controlled conditions (low and high activity). Covariates included in the
      analysis were altitude, time at altitude, activity level, age, body mass index,
      race, sex, and smoking status. RESULTS: AMS severity increased (P < 0.05) nearly
      twofold (i.e., 179%) for every 1000-m increase in altitude at 20 h of exposure,
      peaked between 18 and 22 h of exposure, and returned to initial levels by 48 h of
      exposure regardless of sex or activity level. Peak AMS severity scores were 38%
      higher (P < 0.05) in men compared with women at 20 h of exposure. High active men
      and women (>50% of maximal oxygen uptake for >45 min at altitude) demonstrated a
      72% increase (P < 0.05) in the odds (odds ratio, 1.72; confidence interval, 1.03
      3.08) of AMS compared with low active men and women. There was also a tendency (P
      = 0.10) for men to demonstrate greater odds of AMS (odds ratio, 1.65; confidence
      interval, 0.84-3.25) compared with women. Age, body mass index, race, and smoking
      status were not significantly associated with AMS. CONCLUSIONS: These models
      provide the first quantitative estimates of AMS risk over a wide range of
      altitudes and time points and suggest that in addition to altitude and time at
      altitude, high activity increases the risk of developing AMS. In addition, men
      demonstrated increased severity but not prevalence of AMS.

PMID- 23135374
TI  - Aerobic training workload affects human endothelial cells redox homeostasis.
AB  - PURPOSE: Moderate aerobic exercise reduces oxidative stress, whereas intense
      physical activity may produce the opposite result. At present, the effects of
      different exercise loads on oxidative stress markers and the response of human
      cells to different exercise volumes have not been fully elucidated. METHODS:
      Human (Eahy-926) endothelial cells (EC), exposed or not exposed to oxidative
      stress, were conditioned with sera from two groups of triathletes practicing at
      different workloads. RESULTS: Although no differences in functional and
      hemodynamic variables were observed between the two groups of triathletes,
      significant changes in some markers for oxidative stress were found in their
      sera. Thiobarbituric acid reactive substances and superoxide dismutase activity
      were similar, but triathletes practicing the sport at lower volume (T1) had
      higher serum nitric oxide and lower catalase activity than triathletes performing
      the training at greater load (T2). The EC conditioned with serum from T1 (T1-EC)
      showed higher survival and proliferation rates and lower senescence levels than
      the EC supplemented with T2 (T2-EC) serum both before and after oxidative stress
      induction. These effects depended on catalase as demonstrated via enzyme activity
      inhibition using 3-amino-1,2,4-triazole. After oxidative stress induction, Sirt1
      activity, a regulator of the oxidative stress response, was significantly
      increased in the T1-EC but not in the T2-EC. Moreover, the T1-EC required less
      catalase activity than the T2-EC to counteract an equal amount of oxidative
      stress after H2O2 administration. CONCLUSION: This study demonstrates that the
      beneficial effects of aerobic exercise are eliminated when the training is
      performed at a greater workload. Moreover, we suggest an oxidative stress marker,
      serum catalase activity, as a valid tool to use in the supervision of changes to
      exercise volume.

PMID- 23135375
TI  - Cognition and motor impairment correlates with exercise test performance after
      stroke.
AB  - INTRODUCTION: Exercise not only benefits physical and cardiovascular function in
      older adults with multiple chronic conditions but may also improve cognitive
      function. Peak HR, a physiological indicator for maximal effort, is the most
      common and practical means of establishing and monitoring exercise intensity. In
      particular, in the absence of graded maximal exercise test (GXT) results, age
      predicted maximal HR values are typically used. Using individuals with stroke as
      a model for examining older adults with coexisting cardiovascular and neuromotor
      conditions, the purpose of this article was to examine the determinants
      associated with achieving age-predicted maximal HR on a GXT, with respect to
      neurological, cognitive, and lower limb function. METHODS: Forty-seven
      participants with stroke (age, 67 +/- 7 yr; 4 +/- 3 yr poststroke (mean +/- SD))
      performed GXT. The peak values for gas exchange, HR, and RPE were noted. Logistic
      regression analysis was performed to examine determinants (neurological
      impairment, leg motor impairment, Montreal Cognitive Assessment score, and
      walking ability) associated with the ability to achieve age-predicted maximal HR
      on the GXT. RESULTS: VO2peak was 16.5 +/- 6 mL.kg.min. Fourteen (30%)
      participants achieved >=100% of age-predicted maximal HR. Logistic regression
      modeling revealed that the ability to achieve this threshold was associated with
      less leg motor impairment (P = 0.02; odds ratio, 2.3) and higher cognitive scores
      (P = 0.048; odds ratio, 1.3). CONCLUSIONS: These results suggest that
      noncardiopulmonary factors such as leg motor impairment and cognitive function
      are important contributors to achieving maximal effort during exercise tests.
      This study has important implications for poststroke exercise prescription,
      whereby training intensities that are based on peak HR from GXT may be
      underestimated among individuals with cognitive and physical impairments.

PMID- 23135376
TI  - [Not Available].

PMID- 23135377
TI  - Lowering homocysteine levels may prevent cardiovascular impairments? Possible
      therapeutic behaviors.
AB  - Homocysteine (Hcy) is metabolized through two pathways, requiring folates and B6
      12 vitamins as cofactors. Increased Hcy concentration is responsible for early
      atherosclerosis with possible acute cardiovascular events. Ample evidence has
      demonstrated that Hcy lowering with folic acid and B vitamin supplementation,
      even if reduces Hcy serum levels, is unable to lower cardiovascular risk. On the
      contrary, omega-3 fatty acids and some nutraceuticals, such as N-acetyl cysteine,
      taurine, or S-adenosyl-methionine, reduce both Hcy serum concentration and
      cardiovascular risk. Instead, antiplatelet drugs, such as aspirin and clopidogrel
      or ticlopidine and statins only antagonize vascular derangements. Finally,
      metformin, some lipid-lowering drugs, and some diuretics should be avoided
      because they can increase Hcy levels.

PMID- 23135378
TI  - Are low-molecular-weight heparins appropriately dosed in patients with CKD stage
      3 to 5?
AB  - The aims of this study were to determine the serum antifactor Xa levels in
      patients with impaired glomerular filtration receiving low-molecular-weight
      heparins (LMWHs), monitor efficacy and complications during treatment, and
      determine the approach to dose adjustments of LMWH by using antifactor Xa levels
      in different levels of kidney dysfunction in a real world clinical practice.
      Patients with chronic kidney disease who had subcutaneous enoxaparin
      administration during hospitalization were included in this study. We obtained
      data on patient demographics, glomerular filtration rate, bleeding complications,
      and antifactor Xa levels. Patients were divided into four groups based on
      glomerular filtration rate (>60 ml/min, 30-59 ml/min, 15-29 ml/min, <15 ml/min).
      Target levels for antifactor Xa were accepted as 0.1-0.4 IU/ml for prophylactic
      use and 0.4-1.1 IU/ml for therapeutic use. There were 61 patients and 18 controls
      (40 women, 39 men, mean age 68 +/- 12 years) available for analysis.
      Interpretation of antifactor Xa with regard to target levels has shown that
      levels were in therapeutic range in 33 patients (41.8%), subtherapeutic range in
      38 patients (48.1%), and supratherapeutic range in eight patients (10.1%). Less
      than half of the patients at each level of kidney dysfunction had antifactor Xa
      levels within the therapeutic range. Three patients suffered major bleeding, two
      with supratherapeutic, and one with therapeutic antifactor Xa level. There were
      no complications of ineffective anticoagulation in patients with subtherapeutic
      levels. Inappropriate dosing of LMWH suggested by subtherapeutic and
      supratherapeutic antifactor Xa levels were very high in patients with different
      levels of kidney dysfunction.

PMID- 23135379
TI  - Postmenopausal women have an increased maximal platelet reactivity compared to
      men despite dual antiplatelet therapy.
AB  - Dual antiplatelet medication with acetylsalicylic acid (ASA) and clopidogrel is
      the main therapy for patients with stable coronary vessel disease (CVD) after
      percutaneous coronary intervention (PCI). Despite platelet inhibition subgroups
      of patients have been shown to exhibit an increase of risk for adverse
      cardiovascular events. The aim of our study was to elucidate the influence of sex
      on platelet reactivity in patients with CVD under medication with ASA and
      clopidogrel. Two hundred and thirty patients with CVD on combined therapy with
      ASA (100 mg/day) and clopidogrel (75 mg/day) were included into our study. These
      patients were divided into a male (n = 128) and female (n = 102) group. Platelet
      reactivity was assessed by impedance aggregometry. Women demonstrated a
      significantly higher thrombin receptor-activating peptide (TRAP)-induced platelet
      reactivity than men (male 79.43 +/- 28.55 U vs. female 89.3 +/- 30.69 U; P <
      0.05). The ADP-induced (male 19.81 +/- 15.51 U vs. female 23.73 +/- 17.68 U; P >
      0.05) or arachidonic acid-induced (male 10.3 +/- 12.87 U vs. female 12.76 +/-
      14.44 U; P > 0.05) platelet aggregation did not differ significantly between
      women and men. A multivariate linear regression model revealed female sex to be a
      significant prognostic marker for an increased TRAP-induced platelet reactivity,
      independent of the ASA and clopidogrel-associated platelet function inhibition.
      Sex differences did not influence the effectiveness of ASA or clopidogrel
      mediated platelet function inhibition. Nevertheless, women had a significantly
      increased maximal platelet reactivity compared to men despite antiplatelet
      therapy.

PMID- 23135380
TI  - Coagulation factors and antithrombin levels in young and elderly subjects in
      Pakistani population.
AB  - Aging is associated with increased levels of coagulation factors and decrease in
      natural anticoagulant factors. This strongly supports that age-related
      hypercoagulable state occurs in elderly. This study aimed to measure the plasma
      levels of coagulation factors and anticoagulant levels in young and elderly to
      observe the effect of age on haemostatic system. Ninety healthy individuals, both
      men and women were divided into two groups on the basis of age. Group I included
      participants of less than 40 years of age, whereas, group II comprised of
      participants more than 60 years of age. Fibrinogen activity was assessed by using
      Clauss technique. Coagulation factor VII, and factor VIII activity by
      corresponding one stage assay based on prothrombin time and activated partial
      thromboplastin time. Antithrombin III was measured by the chromogenic method. Our
      results showed that significantly increased levels of fibrinogen (P = 0.001) were
      observed in the elderly population as compared to young. Higher fibrinogen levels
      in younger women than men and comparatively higher level than other races was
      observed in our local population. Increase in factor VII levels (P = 0.05) was
      also observed in the elderly group. This increase was statistically significant
      with age in women (P = 0.03). Factor VIII rose with age in both sexes (P =
      0.001). Higher antithrombin activity was observed in the younger group whereas
      the older group demonstrated significantly lower antithrombin activity (P =
      0.001). We conclude that considerable effects of age and sex are observed on
      coagulation factors and naturally occurring inhibitors.

PMID- 23135381
TI  - Short-term effects of aspirin and clopidogrel on mean platelet volume among
      patients with acute coronary syndromes. A single-center prospective study.
AB  - Mean platelet volume (MPV) has been correlated with platelet reactivity, thus its
      changes might be used to monitor the effects of antiplatelet therapy. However, no
      data have been reported on platelet remodelling after antiplatelet therapy. The
      aim of the current study was to investigate the short-term effects of oral
      antiplatelet therapy on MPV. Our population is represented by 62 consecutive
      patients with acute coronary syndrome (ACS), who did not receive GpIIb-IIIa
      inhibitors. We measured MPV before starting dual antiplatelet therapy, at day 1,
      day 2, and day 3-5 from starting adjunctive antiplatelet therapy. We additionally
      analyzed the relationship between platelet aggregation and MPV at admission by
      Multiplate in patients who were on chronic aspirin therapy. We observed a
      significant paradoxical increase in MPV, with a reduction in platelet count. We
      observed at all time intervals a significant inverse relationship between MPV and
      platelet count (T0: r = -0.44, P < 0.0001; T1: r = -0.36, P = 0.006; T2: r = 
      0.3, P = 0.026; T3-5: r = -0.29, P = 0.046). No relationship was observed between
      MPV and the extent of platelet aggregation inhibition by aspirin. This study
      showed a paradoxical increase in MPV after starting antiplatelet therapy. In
      addition, we did not observe any relationship between baseline MPV and the extent
      of platelet aggregation inhibition by aspirin. Thus, larger MPV does not imply
      higher platelet reactivity and may not be considered to monitor platelet
      reactivity and the efficacy of antiplatelet therapies.

PMID- 23135382
TI  - Intentional low-molecular-weight heparin overdose:  a case report and review.
AB  - The reversal of low-molecular-weight heparins, particularly at supratherapeutic
      levels, remains challenging. The paucity of literature available to guide the
      treatment of these patients makes their management difficult for primary care
      providers, surgeons, and subspecialists alike. We report the case of a 34-year
      old woman, who intentionally overdosed on enoxaparin (Lovenox) in a suicide
      attempt. Her initial antifactor Xa activity level was 8.3 IU/ml, the highest
      level reported in the literature to date. She was initially managed
      conservatively, however, within 24 h of admission she developed evidence of acute
      blood loss. Protamine sulfate and three doses of recombinant activated factor VII
      (rFVIIa) were administered in an effort to control bleeding. We report the
      effects of these measures and review the literature to date. Our study is one of
      the first to graph in-vivo antifactor Xa activity levels and to suggest a drug
      half-life of approximately 25 h.

PMID- 23135383
TI  - The dilemma of inherited dysfibrinogenemia during pregnancy.
AB  - Inherited dysfibrinogenemia is a rare disorder caused by mutations in the
      fibrinogen gene, described in approximately 400 families to date. We present the
      case of a 20-year-old woman at 7 weeks of pregnancy with a history of two first
      trimester spontaneous abortions and a family history of thrombotic events. Her
      testing revealed evidence of dysfibrinogenemia, necessitating multidisciplinary
      management planning including Hematology, OB-GYN, Maternal-Fetal Medicine, Blood
      Bank Services and Anesthesia. Antenatal care included a combination of
      intravenous fibrinogen infusions to maintain fibrinogen levels above 100 mg/dl
      and anticoagulation with low molecular weight heparin. She had an uneventful full
      term delivery and continued fibrinogen infusions and thromboprophylaxis for 6
      weeks postpartum. The combination of fibrinogen infusions and anticoagulation
      maintained the balance between bleeding and clotting in our patient during
      pregnancy. We recommend a multidisciplinary team approach for the management of
      dysfibrinogenemia during pregnancy to provide successful pregnancy outcomes.

PMID- 23135384
TI  - Colorectal carcinoma and folate.
AB  - More than a million people a year worldwide develops colorectal cancer (CRC),
      with a mortality rate close to 33%. Most of the CRC cases are sporadic, only 25%
      of the patients have a family history of the disease, and major genes causing
      syndromes predisposing to CRC only account for 5-6% of the total cases. The
      following subtypes can be recognized: MIN (microsatellite instability), CIN
      (chromosomal instability), and CIMP (CpG island methylator phenotype). CRC arises
      from an accumulation of genetic and epigenetic alterations such as DNA
      methylation, which is able to modulate gene expression. Several studies in the
      literature show a possible correlation between an altered methylation in the
      promoter of tumor suppressor genes, proto-oncogenes, genes involved in DNA repair
      and the CRC risk; it has also been observed a global DNA hypomethylation,
      especially in the presence of a low folate uptake. Epigenetic changes are
      reversible, then could be interesting to evaluate on their relationship with
      dietary factors (as well as folates) and the genetic background of the
      individuals, for the development of novel strategies for cancer prevention.

PMID- 23135385
TI  - Formal gamma-alkynylation of ketones via Pd-catalyzed C-C cleavage.
AB  - A formal gamma-alkynylation of ketones via Pd-catalyzed C-C bond-cleavage is
      presented. The method allows for the coupling of tert-cyclobutanols and
      bromoacetylenes, giving access to versatile alkynes that are beyond reach
      otherwise.

PMID- 23135386
TI  - Polycrystallinity and stacking in CVD graphene.
AB  - Graphene, a truly two-dimensional hexagonal lattice of carbon atoms, possesses
      remarkable properties not seen in any other material, including ultrahigh
      electron mobility, high tensile strength, and uniform broadband optical
      absorption. While scientists initially studied its intrinsic properties with
      small, mechanically exfoliated graphene crystals found randomly, applying this
      knowledge would require growing large-area films with uniform structural and
      physical properties. The science of graphene has recently experienced
      revolutionary change, mainly due to the development of several large-scale growth
      methods. In particular, graphene synthesis by chemical vapor deposition (CVD) on
      copper is a reliable method to obtain films with mostly monolayer coverage. These
      films are also polycrystalline, consisting of multiple graphene crystals joined
      by grain boundaries. In addition, portions of these graphene films contain more
      than one layer, and each layer can possess a different crystal orientation and
      stacking order. In this Account, we review the structural and physical properties
      that originate from polycrystallinity and stacking in CVD graphene. To begin, we
      introduce dark-field transmission electron microscopy (DF-TEM), a technique which
      allows rapid and accurate imaging of key structural properties, including the
      orientation of individual domains and relative stacking configurations. Using DF
      TEM, one can easily identify "lateral junctions," or grain boundaries between
      adjacent domains, as well as "vertical junctions" from the stacking of graphene
      multilayers. With this technique, we can distinguish between oriented (Bernal or
      rhombohedral) and misoriented (twisted) configurations. The structure of lateral
      junctions in CVD graphene is sensitive to growth conditions and is reflected in
      the material's electrical and mechanical properties. In particular, grain
      boundaries in graphene grown under faster reactant flow conditions have no gaps
      or overlaps, unlike more slowly grown films. These structural differences can
      affect the material's electrical properties: for example, better-connected grain
      boundaries are more electrically conductive. However, grain boundaries in general
      are mechanically weaker than pristine graphene, which is an order of magnitude
      stronger than CVD graphene based on indentation measurements performed with an
      atomic force microscope. Vertical junctions in multilayer CVD graphene have two
      key structural features. First, bilayer graphene (BLG) with Bernal stacking
      exists in two mirrored configurations (AB or AC) that also form isolated domains.
      Similarly, oriented trilayer graphene also has alternating ABA and ABC stacked
      layers. Second, in twisted multilayer graphene, stacked layers lack long-range
      atomic registry and can move freely relative to each other, which generates
      unique optical properties. In particular, an interlayer optical excitation
      produces strong Raman and absorption peaks, dependent on the twist angle. A
      better understanding of the structural and physical properties of grain
      boundaries and multilayers in CVD graphene is central to realizing the full
      potential of graphene in large-scale applications. In addition, these studies
      provide a model for characterizing other layered materials, such as hexagonal
      boron nitride and MoS2, where similar polycrystallinity and stacking are expected
      when grown in large areas.

PMID- 23135387
TI  - Fe-O versus O-O bond cleavage in reactive iron peroxide intermediates of
      superoxide reductase.
AB  - It is generally accepted that the catalytic cycles of superoxide reductases
      (SORs) and cytochromes P450 involve a ferric hydroperoxo intermediate at a
      mononuclear iron center with a coordination sphere consisting of four equatorial
      nitrogen ligands and one axial cysteine thiolate trans to the hydroperoxide.
      However, although SORs and P450s have similar intermediates, SORs selectively
      cleave the Fe-O bond and liberate peroxide, whereas P450s cleave the O-O bond to
      yield a high-valent iron center. This difference has attracted the interest of
      researchers, and is further explored here. Meta hybrid DFT (M06-2X) results for
      the reactivity of the putative peroxo/hydroperoxo reaction intermediates in the
      catalytic cycle of SORs were found to indicate a high-spin preference in all
      cases. An exploration of the energy profiles for Fe-O and O-O bond cleavage in
      all spin states in both ferric and ferrous models revealed that Fe-O bond
      cleavage always occurs more easily than O-O bond cleavage. While O-O bond
      cleavage appears to be thermodynamically and kinetically unfeasible in ferric
      hydrogen peroxide complexes, it could occur as a minor (significantly disfavored)
      side reaction in the interaction of ferrous SOR with hydrogen peroxide.

PMID- 23135388
TI  - Heme orientation modulates histidine dissociation and ligand binding kinetics in
      the hexacoordinated human neuroglobin.
AB  - Neuroglobin (Ngb) is a globin present in the brain and retina of mammals. This
      hexacoordinated hemoprotein binds small diatomic molecules, albeit with lower
      affinity compared with other globins. Another distinctive feature of most
      mammalian Ngb is their ability to form an internal disulfide bridge that
      increases ligand affinity. As often seen for prosthetic heme b containing
      proteins, human Ngb exhibits heme heterogeneity with two alternative heme
      orientations within the heme pocket. To date, no details are available on the
      impact of heme orientation on the binding properties of human Ngb and its
      interplay with the cysteine oxidation state. In this work, we used (1)H NMR
      spectroscopy to probe the cyanide binding properties of different Ngb species in
      solution, including wild-type Ngb and the single (C120S) and triple
      (C46G/C55S/C120S) mutants. We demonstrate that in the disulfide-containing wild
      type protein cyanide ligation is fivefold faster for one of the two heme
      orientations (the A isomer) compared with the other isomer, which is attributed
      to the lower stability of the distal His64-iron bond and reduced steric hindrance
      at the bottom of the cavity for heme sliding in the A conformer. We also
      attribute the slower cyanide reactivity in the absence of a disulfide bridge to
      the tighter histidine-iron bond. More generally, enhanced internal mobility in
      the CD loop bearing the disulfide bridge hinders access of the ligand to heme
      iron by stabilizing the histidine-iron bond. The functional impact of heme
      disorder and cysteine oxidation state on the properties of the Ngb ligand is
      discussed.

PMID- 23135389
TI  - Differential effects of cigarette price changes on adult smoking behaviours.
AB  - BACKGROUND: Raising cigarette prices through taxation is an important policy
      approach to reduce smoking. Yet, cigarette price increases may not be equally
      effective in all subpopulations of smokers. PURPOSE: To examine differing effects
      of state cigarette price changes with individual changes in smoking among smokers
      of different intensity levels. METHODS: Data were derived from the National
      Epidemiologic Survey on Alcohol and Related Conditions, a nationally
      representative sample of US adults originally interviewed in 2001-2002 (Wave 1)
      and re-interviewed in 2004-2005 (Wave 2): 34 653 were re-interviewed in Wave 2,
      and 7068 smokers defined at Wave 1 were included in our study. Mixed effects
      linear regression models were used to assess whether the effects of changes in
      state cigarette prices on changes in daily smoking behaviour differed by level of
      daily smoking. RESULTS: In the multivariable model, there was a significant
      interaction between change in price per pack of cigarettes from Wave 1 to Wave 2
      and the number of cigarettes smoked per day (p=0.044). The more cigarettes smoked
      per day at baseline, the more responsive the smokers were to increases in price
      per pack of cigarettes (ie, number of cigarettes smoked per day was reduced in
      response to price increases). CONCLUSIONS: Our findings that heavier smokers
      successfully and substantially reduced their cigarette smoking behaviours in
      response to state cigarette price increases provide fresh insight to the evidence
      on the effectiveness of higher cigarette prices in reducing smoking.

PMID- 23135391
TI  - Benefits and challenges of linking green infrastructure and highway planning in
      the United States.
AB  - Landscape-level green infrastructure creates a network of natural and semi
      natural areas that protects and enhances ecosystem services, regenerative
      capacities, and ecological dynamism over long timeframes. It can also enhance
      quality of life and certain economic activity. Highways create a network for
      moving goods and services efficiently, enabling commerce, and improving mobility.
      A fundamentally profound conflict exists between transportation planning and
      green infrastructure planning because they both seek to create connected,
      functioning networks across the same landscapes and regions, but transportation
      networks, especially in the form of highways, fragment and disconnect green
      infrastructure networks. A key opportunity has emerged in the United States
      during the last ten years with the promotion of measures to link transportation
      and environmental concerns. In this article we examined the potential benefits
      and challenges of linking landscape-level green infrastructure planning and
      implementation with integrated transportation planning and highway project
      development in the United States policy context. This was done by establishing a
      conceptual model that identified logical flow lines from planning to
      implementation as well as the potential interconnectors between green
      infrastructure and highway infrastructure. We analyzed the relationship of these
      activities through literature review, policy analysis, and a case study of a
      suburban Maryland, USA landscape. We found that regionally developed and adopted
      green infrastructure plans can be instrumental in creating more responsive
      regional transportation plans and streamlining the project environmental review
      process while enabling better outcomes by enabling more targeted mitigation. In
      order for benefits to occur, however, landscape-scale green infrastructure
      assessments and plans must be in place before integrated transportation planning
      and highway project development occurs. It is in the transportation community's
      interests to actively facilitate green infrastructure planning because it creates
      a more predictable environmental review context. On the other hand, for landscape
      level green infrastructure, transportation planning and development is much more
      established and better funded and can provide a means of supporting green
      infrastructure planning and implementation, thereby enhancing conservation of
      ecological function.

PMID- 23135392
TI  - Perception of forest values in the alpine community of trentino region (Italy).
AB  - Values are generally defined as social facts that orientate individual and
      collective actions, and consequently influence political, economic and social
      systems. The evaluation of natural resource values is considered an important
      instrument to support decision making in environmental policy. The forest is an
      important renewable resource that provides a mix of social, economic and
      environmental values for society. The paper presents a survey method to collect
      and analyse individual preferences relating to three macro-categories of forest
      values. The survey method was tested in the Trentino region (north-east of the
      Italian Alps) and will soon be extended to other areas. The results of the
      questionnaires provided evidence that the forest economic value is perceived as
      least important, while the environmental values were appreciated the most.
      Regarding the principle social variables, males tended to give higher scores to
      all three macro-categories compared to females. Moreover, people with a low
      education also gave higher scores to all three categories in comparison to the
      more educated individuals.

PMID- 23135393
TI  - What makes grassroots conservation organizations resilient? An empirical analysis
      of diversity, organizational memory, and the number of leaders.
AB  - Conservation Area Management Committees (CAMCs)-the functional decision-making
      units consisting entirely of local villagers-are grassroots organizations legally
      established to manage the Annapurna Conservation Area (ACA) in Nepal. These
      committees suffered due to the decade-long Maoist insurgency, but they survived.
      The paper attempts to test what factors contributed to their resiliency. For
      this, I surveyed 30 CAMCs during the summer of 2007 and conducted semi-structured
      interviews of 190 executive members of the CAMCs and 13 park officials who
      closely monitor the CAMCs. Regression results showed that the number of leaders
      (b = 0.44, t = 2.38, P = .027) was the most critical variable for building the
      resilience of CAMCs to the Maoist insurgency, i.e., retaining the same function,
      structure, and identity of the committees. As there were no reported conflicts
      among leaders and they were involved in negotiations and devising contingency
      plans, CAMCs actually benefited from having more leaders. Of the three diversity
      indices, the quadratic terms of age diversity (b = -5.42, t = 1.95, P = .064) and
      ethnic diversity (b = -4.05, t = 1.78, P = .075) had a negative impact on the
      CAMCs' resilience. Skill diversity and organizational memory had no significant
      influence on the CAMCs' resilience (t < 1.48, P > .10). These results have
      important implications for building resilience in community-based conservation.

PMID- 23135394
TI  - Active matter: Spontaneous flows and self-propelled drops.

PMID- 23135395
TI  - Identification of a rudimentary neural crest in a non-vertebrate chordate.
AB  - Neural crest arises at the neural plate border, expresses a core set of
      regulatory genes and produces a diverse array of cell types, including
      ectomesenchyme derivatives that elaborate the vertebrate head. The evolution of
      neural crest has been proposed to be a key event leading to the appearance of new
      cell types that fostered the transition from filter feeding to active predation
      in ancestral vertebrates. However, the origin of neural crest remains
      controversial, as homologous cell types have not been unambiguously identified in
      non-vertebrate chordates. Here we show that the tunicate Ciona intestinalis
      possesses a cephalic melanocyte lineage (a9.49) similar to neural crest that can
      be reprogrammed into migrating 'ectomesenchyme' by the targeted misexpression of
      Twist (also known as twist-like 2). Our results suggest that the neural crest
      melanocyte regulatory network pre-dated the divergence of tunicates and
      vertebrates. We propose that the co-option of mesenchyme determinants, such as
      Twist, into the neural plate ectoderm was crucial to the emergence of the
      vertebrate 'new head'.

PMID- 23135396
TI  - Zero-valent sulphur is a key intermediate in marine methane oxidation.
AB  - Emissions of methane, a potent greenhouse gas, from marine sediments are
      controlled by anaerobic oxidation of methane coupled primarily to sulphate
      reduction (AOM). Sulphate-coupled AOM is believed to be mediated by a consortium
      of methanotrophic archaea (ANME) and sulphate-reducing Deltaproteobacteria but
      the underlying mechanism has not yet been resolved. Here we show that zero-valent
      sulphur compounds (S(0)) are formed during AOM through a new pathway for
      dissimilatory sulphate reduction performed by the methanotrophic archaea. Hence,
      AOM might not be an obligate syntrophic process but may be carried out by the
      ANME alone. Furthermore, we show that the produced S(0)--in the form of
      disulphide--is disproportionated by the Deltaproteobacteria associated with the
      ANME. Our observations expand the diversity of known microbially mediated sulphur
      transformations and have significant implications for our understanding of the
      biogeochemical carbon and sulphur cycles.

PMID- 23135397
TI  - Palaeoanthropology: Sharpening the mind.

PMID- 23135398
TI  - The MU transpososome structure sheds light on DDE recombinase evolution.
AB  - Studies of bacteriophage Mu transposition paved the way for understanding
      retroviral integration and V(D)J recombination as well as many other DNA
      transposition reactions. Here we report the structure of the Mu transpososome--Mu
      transposase (MuA) in complex with bacteriophage DNA ends and target DNA-
      determined from data that extend anisotropically to 5.2 A, 5.2 A and 3.7 A
      resolution, in conjunction with previously determined structures of individual
      domains. The highly intertwined structure illustrates why chemical activity
      depends on formation of the synaptic complex, and reveals that individual domains
      have different roles when bound to different sites. The structure also provides
      explanations for the increased stability of the final product complex and for its
      preferential recognition by the ATP-dependent unfoldase ClpX. Although MuA and
      many other recombinases share a structurally conserved 'DDE' catalytic domain,
      comparisons among the limited set of available complex structures indicate that
      some conserved features, such as catalysis in trans and target DNA bending, arose
      through convergent evolution because they are important for function.

PMID- 23135399
TI  - Revealing the quantum regime in tunnelling plasmonics.
AB  - When two metal nanostructures are placed nanometres apart, their optically driven
      free electrons couple electrically across the gap. The resulting plasmons have
      enhanced optical fields of a specific colour tightly confined inside the gap.
      Many emerging nanophotonic technologies depend on the careful control of this
      plasmonic coupling, including optical nanoantennas for high-sensitivity chemical
      and biological sensors, nanoscale control of active devices, and improved
      photovoltaic devices. But for subnanometre gaps, coherent quantum tunnelling
      becomes possible and the system enters a regime of extreme non-locality in which
      previous classical treatments fail. Electron correlations across the gap that are
      driven by quantum tunnelling require a new description of non-local transport,
      which is crucial in nanoscale optoelectronics and single-molecule electronics.
      Here, by simultaneously measuring both the electrical and optical properties of
      two gold nanostructures with controllable subnanometre separation, we reveal the
      quantum regime of tunnelling plasmonics in unprecedented detail. All observed
      phenomena are in good agreement with recent quantum-based models of plasmonic
      systems, which eliminate the singularities predicted by classical theories. These
      findings imply that tunnelling establishes a quantum limit for plasmonic field
      confinement of about 10(-8)lambda(3) for visible light (of wavelength lambda).
      Our work thus prompts new theoretical and experimental investigations into
      quantum-domain plasmonic systems, and will affect the future of nanoplasmonic
      device engineering and nanoscale photochemistry.

PMID- 23135400
TI  - Microbiology: A piece of the methane puzzle.

PMID- 23135401
TI  - Structure of a force-conveying cadherin bond essential for inner-ear
      mechanotransduction.
AB  - Hearing and balance use hair cells in the inner ear to transform mechanical
      stimuli into electrical signals. Mechanical force from sound waves or head
      movements is conveyed to hair-cell transduction channels by tip links, fine
      filaments formed by two atypical cadherins known as protocadherin 15 and cadherin
      23 (refs 4, 5). These two proteins are involved in inherited deafness and feature
      long extracellular domains that interact tip-to-tip in a Ca(2+)-dependent manner.
      However, the molecular architecture of this complex is unknown. Here we combine
      crystallography, molecular dynamics simulations and binding experiments to
      characterize the protocadherin 15-cadherin 23 bond. We find a unique cadherin
      interaction mechanism, in which the two most amino-terminal cadherin repeats
      (extracellular cadherin repeats 1 and 2) of each protein interact to form an
      overlapped, antiparallel heterodimer. Simulations predict that this tip-link bond
      is mechanically strong enough to resist forces in hair cells. In addition, the
      complex is shown to become unstable in response to Ca(2+) removal owing to
      increased flexure of Ca(2+)-free cadherin repeats. Finally, we use structures and
      biochemical measurements to study the molecular mechanisms by which deafness
      mutations disrupt tip-link function. Overall, our results shed light on the
      molecular mechanics of hair-cell sensory transduction and on new interaction
      mechanisms for cadherins, a large protein family implicated in tissue and organ
      morphogenesis, neural connectivity and cancer.

PMID- 23135402
TI  - Spontaneous motion in hierarchically assembled active matter.
AB  - With remarkable precision and reproducibility, cells orchestrate the cooperative
      action of thousands of nanometre-sized molecular motors to carry out mechanical
      tasks at much larger length scales, such as cell motility, division and
      replication. Besides their biological importance, such inherently non-equilibrium
      processes suggest approaches for developing biomimetic active materials from
      microscopic components that consume energy to generate continuous motion. Being
      actively driven, these materials are not constrained by the laws of equilibrium
      statistical mechanics and can thus exhibit sought-after properties such as
      autonomous motility, internally generated flows and self-organized beating. Here,
      starting from extensile microtubule bundles, we hierarchically assemble far-from
      equilibrium analogues of conventional polymer gels, liquid crystals and
      emulsions. At high enough concentration, the microtubules form a percolating
      active network characterized by internally driven chaotic flows, hydrodynamic
      instabilities, enhanced transport and fluid mixing. When confined to emulsion
      droplets, three-dimensional networks spontaneously adsorb onto the droplet
      surfaces to produce highly active two-dimensional nematic liquid crystals whose
      streaming flows are controlled by internally generated fractures and self
      healing, as well as unbinding and annihilation of oppositely charged disclination
      defects. The resulting active emulsions exhibit unexpected properties, such as
      autonomous motility, which are not observed in their passive analogues. Taken
      together, these observations exemplify how assemblages of animate microscopic
      objects exhibit collective biomimetic properties that are very different from
      those found in materials assembled from inanimate building blocks, challenging us
      to develop a theoretical framework that would allow for a systematic engineering
      of their far-from-equilibrium material properties.

PMID- 23135403
TI  - Mitochondrial Atpif1 regulates haem synthesis in developing erythroblasts.
AB  - Defects in the availability of haem substrates or the catalytic activity of the
      terminal enzyme in haem biosynthesis, ferrochelatase (Fech), impair haem
      synthesis and thus cause human congenital anaemias. The interdependent functions
      of regulators of mitochondrial homeostasis and enzymes responsible for haem
      synthesis are largely unknown. To investigate this we used zebrafish genetic
      screens and cloned mitochondrial ATPase inhibitory factor 1 (atpif1) from a
      zebrafish mutant with profound anaemia, pinotage (pnt (tq209)). Here we describe
      a direct mechanism establishing that Atpif1 regulates the catalytic efficiency of
      vertebrate Fech to synthesize haem. The loss of Atpif1 impairs haemoglobin
      synthesis in zebrafish, mouse and human haematopoietic models as a consequence of
      diminished Fech activity and elevated mitochondrial pH. To understand the
      relationship between mitochondrial pH, redox potential, [2Fe-2S] clusters and
      Fech activity, we used genetic complementation studies of Fech constructs with or
      without [2Fe-2S] clusters in pnt, as well as pharmacological agents modulating
      mitochondrial pH and redox potential. The presence of [2Fe-2S] cluster renders
      vertebrate Fech vulnerable to perturbations in Atpif1-regulated mitochondrial pH
      and redox potential. Therefore, Atpif1 deficiency reduces the efficiency of
      vertebrate Fech to synthesize haem, resulting in anaemia. The identification of
      mitochondrial Atpif1 as a regulator of haem synthesis advances our understanding
      of the mechanisms regulating mitochondrial haem homeostasis and red blood cell
      development. An ATPIF1 deficiency may contribute to important human diseases,
      such as congenital sideroblastic anaemias and mitochondriopathies.

PMID- 23135404
TI  - Novel Foxo1-dependent transcriptional programs control T(reg) cell function.
AB  - Regulatory T (T(reg)) cells, characterized by expression of the transcription
      factor forkhead box P3 (Foxp3), maintain immune homeostasis by suppressing self
      destructive immune responses. Foxp3 operates as a late-acting differentiation
      factor controlling T(reg) cell homeostasis and function, whereas the early T(reg)
      cell-lineage commitment is regulated by the Akt kinase and the forkhead box O
      (Foxo) family of transcription factors. However, whether Foxo proteins act beyond
      the T(reg)-cell-commitment stage to control T(reg) cell homeostasis and function
      remains largely unexplored. Here we show that Foxo1 is a pivotal regulator of
      T(reg )cell function. T(reg) cells express high amounts of Foxo1 and display
      reduced T-cell-receptor-induced Akt activation, Foxo1 phosphorylation and Foxo1
      nuclear exclusion. Mice with T(reg)-cell-specific deletion of Foxo1 develop a
      fatal inflammatory disorder similar in severity to that seen in Foxp3-deficient
      mice, but without the loss of T(reg) cells. Genome-wide analysis of Foxo1 binding
      sites reveals ~300 Foxo1-bound target genes, including the pro-inflammatory
      cytokine Ifng, that do not seem to be directly regulated by Foxp3. These findings
      show that the evolutionarily ancient Akt-Foxo1 signalling module controls a novel
      genetic program indispensable for T(reg) cell function.

PMID- 23135405
TI  - An early and enduring advanced technology originating 71,000 years ago in South
      Africa.
AB  - There is consensus that the modern human lineage appeared in Africa before
      100,000 years ago. But there is debate as to when cultural and cognitive
      characteristics typical of modern humans first appeared, and the role that these
      had in the expansion of modern humans out of Africa. Scientists rely on
      symbolically specific proxies, such as artistic expression, to document the
      origins of complex cognition. Advanced technologies with elaborate chains of
      production are also proxies, as these often demand high-fidelity transmission and
      thus language. Some argue that advanced technologies in Africa appear and
      disappear and thus do not indicate complex cognition exclusive to early modern
      humans in Africa. The origins of composite tools and advanced projectile weapons
      figure prominently in modern human evolution research, and the latter have been
      argued to have been in the exclusive possession of modern humans. Here we
      describe a previously unrecognized advanced stone tool technology from Pinnacle
      Point Site 5-6 on the south coast of South Africa, originating approximately
      71,000 years ago. This technology is dominated by the production of small
      bladelets (microliths) primarily from heat-treated stone. There is agreement that
      microlithic technology was used to create composite tool components as part of
      advanced projectile weapons. Microliths were common worldwide by the mid-Holocene
      epoch, but have a patchy pattern of first appearance that is rarely earlier than
      40,000 years ago, and were thought to appear briefly between 65,000 and 60,000
      years ago in South Africa and then disappear. Our research extends this record to
      ~71,000 years, shows that microlithic technology originated early in South
      Africa, evolved over a vast time span (~11,000 years), and was typically coupled
      to complex heat treatment that persisted for nearly 100,000 years. Advanced
      technologies in Africa were early and enduring; a small sample of excavated sites
      in Africa is the best explanation for any perceived 'flickering' pattern.

PMID- 23135406
TI  - Evodiamine activates autophagy as a cytoprotective response in murine Lewis lung
      carcinoma cells.
AB  - Autophagy is a self-defense mechanism that provides nutrition and energy for cell
      survival by recycling the cytoplasm and organelles. Hence, chemotherapy is
      rendered less effective against cancer cells. Evodiamine is a previously
      described biological agent that possesses a cytotoxic activity in multiple cancer
      cells. However, little is known about evodiamine-induced autophagy in Lewis lung
      carcinoma (LLC) cells. In this study, LLC cells and a xenograft model were used.
      By use of a panel of techniques such as MTT assay, flow cytometry, western
      blotting, immunocytochemistry and TUNEL assay, the effects on the induction of
      apoptosis and autophagy were evaluated. We demonstrated that evodiamine inhibited
      LLC cell growth and induced apoptosis through caspase-independent manner in vitro
      and caspase-dependent pathway in vivo. In addition, we showed for the first time
      that evodiamine promoted autophagosome formation by enhancing the conversion of
      microtubule-associated protein 1 light chain 3 (LC3)-I to LC3-II and upregulating
      the expression of autophagy-specific genes (Atgs). Moreover, 3-methyladenine (3
      MA), an autophagy inhibitor, attenuated evodiamine-induced autophagy through
      decreasing the conversion of LC3-I to LC3-II. The inhibition of autophagy was
      found to increase cell death and enhance evodiamine-induced apoptosis in vitro in
      a caspase-independent manner and in vivo in a caspase-dependent manner. In
      conclusion, evodiamine promoted autophagy in LLC cells and autophagy inhibition
      enhanced evodiamine-induced apoptosis in vitro and in vivo. These results
      demonstrate that evodiamine-induced autophagy plays a cytoprotective role in LLC
      cells and evodiamine combined with autophagy inhibitor therapy could increase the
      chemosensitivity of LLC cells.

PMID- 23135407
TI  - Characterization of atrial histopathological and electrophysiological changes in
      a mouse model of aging.
AB  - The detailed mechanisms of age-related atrial structural and electrophysiological
      changes remain elusive. Small animal models have recently been used for the
      investigation of atrial tachyarrhythmia. In this study, we investigated the
      hypothesis that atrial structural and electrical characterization with aging
      provides a substrate for atrial fibrillation using a mouse model of aging. Male
      Kunming mice aged 2 (young), 12 (middle-aged) and 24 months (aged) were used in
      this study. A surface electrocardiogram and sinus node recovery time (SNRT) were
      recorded at baseline. Atrial fibrillation (AF) inducibility and duration were
      measured by a transesophageal electrode catheter. Collagen content was assessed
      by the collagen volume fraction. Whole cell configuration using the patch clamp
      technique was performed for the transient outward potassium (Ito) and ultra-rapid
      delayed rectifier potassium (Ikur) currents. P-wave duration, SNRT and rate
      corrected SNRT were longer in the aged group than in the remaining 2 groups,
      paralleled by inducibility significantly being increased in the aged group. The
      right atrium had significantly higher levels of fibrosis than the left atrium in
      all the groups (P<0.05), whereas the extent of fibrosis in the left atrium had a
      higher positive correlation with age relative to the right atrium (P<0.05).
      Moreover, in old age, the dispersion of left relative to right atrium
      repolarization and augmented Ito currents contributed to vulnerability to AF.
      Nevertheless, Ikur currents in the atrial myocytes showed no age-related changes.
      The present study demonstrates that in addition to the structural alterations,
      aging can also cause integrative and cellular electrophysiological changes in a
      mouse model of aging, facilitating AF initiation and maintenance.

PMID- 23135409
TI  - Batch-reactor microfluidic device: first human use of a microfluidically produced
      PET radiotracer.
AB  - The very first microfluidic device used for the production of (18)F-labeled
      tracers for clinical research is reported along with the first human Positron
      Emission Tomography scan obtained with a microfluidically produced radiotracer.
      The system integrates all operations necessary for the transformation of
      [(18)F]fluoride in irradiated cyclotron target water to a dose of
      radiopharmaceutical suitable for use in clinical research. The key microfluidic
      technologies developed for the device are a fluoride concentration system and a
      microfluidic batch reactor assembly. Concentration of fluoride was achieved by
      means of absorption of the fluoride anion on a micro ion-exchange column (5 MUL
      of resin) followed by release of the radioactivity with 45 MUL of the release
      solution (95 +/- 3% overall efficiency). The reactor assembly includes an
      injection-molded reactor chip and a transparent machined lid press-fitted
      together. The resulting 50 MUL cavity has a unique shape designed to minimize
      losses of liquid during reactor filling and liquid evaporation. The cavity has 8
      ports for gases and liquids, each equipped with a 2-way on-chip mechanical valve
      rated for pressure up to 20.68 bar (300 psi). The temperature is controlled by a
      thermoelectric heater capable of heating the reactor up to 180  degrees C from RT
      in 150 s. A camera captures live video of the processes in the reactor. HPLC
      based purification and reformulation units are also integrated in the device. The
      system is based on "split-box architecture", with reagents loaded from outside of
      the radiation shielding. It can be installed either in a standard hot cell, or as
      a self-shielded unit. Along with a high level of integration and automation,
      split-box architecture allowed for multiple production runs without the user
      being exposed to radiation fields. The system was used to support clinical trials
      of [(18)F]fallypride, a neuroimaging radiopharmaceutical under IND Application
      #109,880.

PMID- 23135410
TI  - Evaluation of collagen/heparin coated TCP/HA granules for long-term delivery of
      BMP-2.
AB  - Bone morphogenetic proteins (BMPs) are the most potent osteoinductive growth
      factors. However, a delivery system is essential to take advantage of the
      osteoinductive effect of BMPs. The purpose of this study was to develop a
      sustained delivery system for recombinant human bone morphogenetic protein-2 (BMP
      2). We covalently attached heparin to a cross-linked collagen type I coated
      tricalciumphosphate/hydroxyapatite (TCP/HA) bone substitute and subsequently
      loaded it with BMP-2. To systematically evaluate the contribution of each
      component with respect to the binding and release of BMP-2, six constructs were
      prepared and characterized: TCP/HA, TCP/HA with collagen (TCP/HACol), and TCP/HA
      with collagen and heparin (TCP/HAColHep) with and without BMP-2 (B). More BMP-2
      bound to the TCP/HAColHep + B (92.9 +/- 4.8 ng BMP-2/mg granule) granules as
      compared to the TCP/HACol + B (69.0 +/- 9.6 ng BMP-2/mg granule) and TCP/HA + B
      granules (62.9 +/- 5.4 ng BMP-2/mg granule). No difference in release pattern was
      found between the TCP/HA + B and TCP/HACol + B granules. Up to day 14, BMP-2 was
      still bound to the TCP/HAColHep + B granules, whereas most BMP had been released
      from TCP/HACol + B and TCP/HA + B granules at that time. After 21 days most BMP-2
      also had been released from the TCP/HAColHep + B granules. The local and
      sustained delivery system for BMP-2 developed in this study may be useful as a
      carrier for BMP-2 and could possibly enhance bone regeneration efficacy for the
      treatment of large bone defects.

PMID- 23135411
TI  - Aspirin-loaded electrospun poly(epsilon-caprolactone) tubular scaffolds:
      potential small-diameter vascular grafts for thrombosis prevention.
AB  - Thrombosis is the main cause of failure of small-diameter synthetic vascular
      grafts when used for by-pass procedures. The development of bioresorbable
      vascular scaffolds with localized and sustained intra-luminal antithrombotic drug
      release could be considered a desirable improvement towards a valuable solution
      for this relevant clinical need. For this aim, we present the fabrication and
      characterization of aspirin-loaded electrospun poly(epsilon-caprolactone) tubular
      scaffolds as a vascular drug-delivery graft. Three different drug concentrations
      were considered (i.e., 1, 5 or 10 % w/w). Although a fibrous structure was
      clearly observed for all the collected scaffolds, aspirin content was directly
      implied in the final microstructure leading to a bimodal fiber diameter
      distribution and fused fibers at crossing-points (5 or 10 % w/w). Mechanical
      response highlighted a direct relationship for modulus and stress at break with
      the aspirin content, while the elongation at break was not remarkably different
      for the investigated cases. The temporal drug release was strongly dependent from
      the amount of loaded aspirin, reaching a steady state release after about 50 h.
      Finally, the adhesion assay confirmed the capability of the electrospun scaffolds
      to reduce platelet adhesion/aggregation onto aspirin loaded polymeric fibers.
      Aspirin-loaded electrospun tubular scaffold could represent a feasible candidate
      to develop a novel bioresorbable drug-releasing graft for small-diameter vessel
      replacements.

PMID- 23135412
TI  - A novel cyclic RGD-containing peptide polymer improves serum-free adhesion of
      adipose tissue-derived mesenchymal stem cells to bone implant surfaces.
AB  - Seeding of bone implants with mesenchymal stem cells (MSCs) may promote
      osseointegration and bone regeneration. However, implant material surfaces, such
      as titanium or bovine bone mineral, fail to support rapid and efficient
      attachment of MSCs, especially under serum-free conditions that may be desirable
      when human applications or tightly controlled experiments are envisioned. Here we
      demonstrate that a branched poly[Lys(Ser(i)-DL-Ala(m))] polymer functionalized
      with cyclic arginyl-glycyl-aspartate, when immobilized by simple adsorption to
      tissue culture plastic, surgical titanium alloy (Ti6Al4V), or Bio-Oss((r)) bovine
      bone substitute, significantly accelerates serum-free adhesion and enhances
      seeding efficiency of human adipose tissue-derived MSCs. Moreover, when exposed
      to serum-containing osteogenic medium, MSCs survived and differentiated on the
      peptide-coated scaffolds. In summary, the presented novel polypeptide conjugate
      can be conveniently used for coating various surfaces, and may find applications
      whenever quick and efficient seeding of MSCs is required to various scaffolds in
      the absence of serum.

PMID- 23135413
TI  - Similar survival between screw cementless and cemented tibial components in young
      patients with osteoarthritis.
AB  - PURPOSE: The aim of this study was to compare the outcomes of tibial fixation
      with either a cemented or cementless with screw augmentation component in young
      patients with non-inflammatory arthritis. METHODS: Ninety-three patients aged 55
      or younger with non-inflammatory arthritis were randomized to compare outcomes
      between cemented tibial fixation (48 patients) and cementless fixation with screw
      augmentation (45 patients). The femoral component was cementless in both groups.
      Post-operative evaluation was assessed by the clinical and radiological criteria
      of The Knee Society and WOMAC questionnaire. RESULTS: The median follow-up was
      6.7 (5-12) years. Significant differences were found for knee score (p = 0.02),
      range of motion (p = 0.04), and WOMAC score (p = 0.03). In the cemented group,
      there was one deep wound infection, four tibial aseptic loosening, and one
      polyethylene wear, all of which were revised. In the cementless group there was
      one tibial aseptic loosening and one polyethylene wear, both being revised. There
      was no difference in revision rate, and the cumulative survival at 9-year for
      aseptic reason was 93.7 % (95 % CI, 82-100 %) in the cementless group and 90.0 %
      (95 % CI, 80-100 %) in the cemented group (n.s.). CONCLUSIONS: Cementless total
      knee arthroplasty was found to be a reliable option in younger patients with
      osteoarthritis. Although the revision rate and survival were similar in both
      groups, better clinical outcomes were obtained with cementless tibial components.

PMID- 23135414
TI  - Patella infera or patellar tendon adherence after high tibial osteotomy.
AB  - PURPOSE: Alterations in patellar height after high tibial osteotomy are found in
      many instances. Fibrosis of the tendon is implicated as the cause of the
      mechanism of patella lowering. This study aimed to determine the relationship
      between the position of the patella and the histopathological findings at the
      patellar tendon after high tibial osteotomy. METHODS: Nineteen knees in seventeen
      patients who were consecutively hospitalised for implant extraction are studied.
      All of the patients had previously undergone closing wedge osteotomy by the same
      surgeon at the same department. The median follow-up time is 15 months (range: 11
      35). Five patients who all underwent high tibial osteotomy at the same time are
      also included in the study as a control group for histopathological evaluation.
      All of the patients are evaluated radiologically, patellar tendon biopsies are
      taken during the operation, and histopathological analyses are performed.
      RESULTS: The shortening of the patellar tendon is statistically significant (P <
      0.05). The severity of the vascularisation, inflammation, and fibrotic change
      observed at the distal part of the tendon is evident. However, there is no
      statistically significant correlation between these findings and the degree of
      shortening. CONCLUSIONS: The shortening of the tendon occurs as a result of
      adherence in the distal part of the tendon. It would appear that it is this
      shortening that causes the difficulties encountered during arthroplasty surgery
      of osteotomy patients, and not patella infera.

PMID- 23135415
TI  - Kidney transplantation and large anastomotic pseudoaneurysm. Transplant
      management considerations.
AB  - AIM: Pseudoaneurysm (PA) at the anastomosis site in kidney transplantation is a
      rare but serious complication that usually requires graft nephrectomy. Literature
      reports are sporadic and usually focused on limb rather than graft salvage. In
      this paper we focus on this last point. MATERIAL OF STUDY: 6 patients presenting
      large PA at the anastomosis between iliac and graft artery were identified in our
      series. The diagnosis was performed with US, AngioTC scan and angiography. Blood
      cultures and labeled leukocyte scintigraphy were also performed. All patients
      underwent open surgery. RESULTS: Transplant nephrectomy was needed in all cases
      except one, in which it was possible to perform a graft replanting on hypogastric
      artery. Our perioperative mortality and morbidity rate was recorded. DISCUSSION:
      Etiology of PA is multifactorial, however an association with chronic rejection
      or infection must be also considered. Our mortality and morbidity rates are in
      accordance to literature. In our experience we observed only large PA so to
      require an open surgery but this approach has allowed the rescue of graft
      functioning just in a single case. Endovascular procedures are linked to higher
      rate of graft salvage than surgery but they can be used just in selected cases.
      CONCLUSIONS: Our experience and literature review led us to believe that the rate
      of graft salvage in patients with large PA at anastomosis site could be improved
      only by a planned therapeutic program that includes surgical and endovascular
      approach, taking the advantages of both technique and overcoming their limits.

PMID- 23135416
TI  - Endocrine, metabolic, and morphologic alterations of adipose tissue during
      critical illness.
AB  - OBJECTIVE: Observational studies report lower mortality in obese than in lean
      critically ill patients, an association referred to as the "obesity paradox."
      This may suggest a possible protective role for adipose tissue during severe
      illness. DATA SOURCES: Relevant publications were identified based on searches in
      PubMed and on secondary searches of their bibliographies. DATA SYNTHESIS: The
      endocrine functions of adipose tissue might play a role in the adaptation to
      critical illness. In the acute phase of illness, the anti-inflammatory
      adiponectin is reduced, whereas proinflammatory cytokine expression in adipose
      tissue is up-regulated. In the prolonged phase of critical illness, both
      adiponectin and anti-inflammatory cytokine production are increasing. Studies on
      the proinflammatory adipokine leptin during critical illness are inconsistent,
      possibly due to confounders such as gender, body mass index, and feeding.
      Morphologically, adipose tissue of critically ill patients reveals an increased
      number of newly differentiated, smaller adipocytes. Accentuated macrophage
      accumulation showing a phenotypic switch to M2-type suggests an adaptive response
      to the microenvironment of severe illness. Functionally, adipose tissue of
      critically ill patients develops an increased ability to store glucose and
      triglycerides. CONCLUSIONS: Endocrine, metabolic, and morphologic properties of
      adipose tissue change during critical illness. These alterations may suggest a
      possible adaptive, protective role in optimizing chances of survival. More
      research is needed to understand the exact role of adipose tissue in lean vs.
      obese critically ill patients, in order to understand how illness-associated
      alterations contribute to the obesity paradox.

PMID- 23135418
TI  - Comfort with my own demise.

PMID- 23135419
TI  - Effects of the implementation of an evidence-based program to manage concerns
      about falls in older adults.
AB  - PURPOSE OF THE STUDY: Concerns about falls and related activity avoidance are
      common in older people. A multicomponent program reduced these concerns and
      increased daily activity among older people in a randomized controlled trial.
      This study explored whether the effects and acceptability of the program maintain
      after its implementation into home care organizations. DESIGN AND METHODS: In a
      pretest-post-test study, the effects and acceptability of the 8-week cognitive
      behavioral program was evaluated in 125 community-living older adults. Data on
      concerns about falls, related avoidance behavior, falls, fall-related medical
      attention, feelings of loneliness and anxiety, and symptoms of depression were
      collected prior to the start of the program and at 2 and 4 months. RESULTS:
      Pretest-post-test analyses showed significant improvements at 4 months for
      concerns about falls, activity avoidance, number of falls in the past 2 months,
      feelings of anxiety, and symptoms of depression. No significant differences were
      shown for daily activity, feelings of loneliness, and fall-related medical
      attention. IMPLICATIONS: After implementation in home care organizations, the
      program reduced concerns about falls, avoidance behavior, and falls in community
      living older adults. These findings are highly consistent with the outcomes of a
      previously performed randomized controlled trial, indicating that the program can
      be successfully implemented in practice. Further dissemination of the program is
      recommended to reduce concerns about falls and related activity avoidance in
      community-living older people.

PMID- 23135420
TI  - Copper-catalyzed multicomponent coupling/cycloisomerization reaction between
      substituted 1-formyl-9H-beta-carbolines, secondary amines, and substituted
      alkynes for the synthesis of substituted 3-aminoindolizino[8,7-b]indoles.
AB  - A copper-catalyzed efficient one step three component strategy for preparing a
      library of aminoindolizino[8,7-b]indoles from N-substituted 1-formyl-9H-beta
      carbolines, secondary amines, and substituted alkynes with high atom economy has
      been developed.

PMID- 23135421
TI  - Incidence and risk factors of the intraoperative localization failure of
      nonpalpable breast lesions by radio-guided occult lesion localization: a
      retrospective analysis of 579 cases: reply.

PMID- 23135422
TI  - Multifocality, but not bilaterality, is a predictor of disease
      recurrence/persistence of papillary thyroid carcinoma.
AB  - BACKGROUND: Although papillary thyroid carcinoma (PTC) often presents as
      multifocal or bilateral tumors, but whether multifocality or bilaterality is
      associated with disease recurrence/persistence is controversial. We evaluated the
      association between multifocality and bilaterality of PTC and disease
      recurrence/persistence. We also analyzed the location and number of tumors in
      multifocal PTC. METHODS: We reviewed the medical records of 2,095 patients who
      underwent total thyroidectomy for PTC. Tumors were classified as solitary or
      multifocal PTC according to the number of tumors present. Multifocal PTCs were
      subdivided into multifocal-unilateral and multifocal-bilateral PTC based on the
      tumor location. Solitary tumor or multifocal tumors located in one lobe were
      classified as unilateral PTC, and tumors in both lobes were classified as
      bilateral PTC. We analyzed the clinicopathologic features and clinical outcomes
      in each classification. Logistic regression models were used to assess the
      relation between multifocality or bilaterality and disease
      recurrence/persistence. RESULTS: Extrathyroidal invasion, cervical lymph node
      metastasis, and advanced TNM stage were significantly more frequent in multifocal
      PTC than in solitary PTC. Extrathyroidal invasion, cervical lymph node
      metastasis, advanced TNM stage, and distant metastasis were significantly more
      frequent in bilateral PTC than in unilateral PTC. The clinicopathologic
      parameters did not differ significantly between patients with multifocal
      unilateral and multifocal-bilateral PTC. Multifocality was found to be an
      independent predictor of disease recurrence/persistence [odds ratio (OR) 1.45, 95
      % confidence interval (CI) 1.01-2.10, p = 0.04]. However, there was no
      association between bilaterality and disease recurrence/persistence (OR 0.98, 95
      % CI 0.64-1.48, p = 0.92). In multifocal PTC, the number of tumors (OR 1.75, 95 %
      CI 1.04-2.97, p = 0.04), but not the location of tumors (OR 0.56, 95 % CI 0.31
      1.02, p = 0.06), was significantly associated with disease
      recurrence/persistence. CONCLUSIONS: Although multifocal and bilateral PTC had
      aggressive pathologic features, only multifocality was associated with an
      increased risk of disease recurrence/persistence. This suggests that the number
      of tumor foci, but not their location, is a significant predictor of clinical
      outcomes.

PMID- 23135423
TI  - Long-term follow-up of the "wait and see" approach to localized perinatal adrenal
      neuroblastoma.
AB  - BACKGROUND: Evidence-based guidelines for the management of localized perinatal
      adrenal neuroblastoma are not yet available. We describe our preliminary
      experience managing this tumor with a "wait and see" policy. METHODS: A single
      center prospective study (February 2002 to December 2009) was conducted with 12
      consecutive patients in whom an adrenal mass was detected antenatally or within
      the first 3 months of life. Diagnostic workup included the following
      investigations: measurement of urine catecholamine metabolites, imaging studies
      (ultrasonography, magnetic resonance imaging, or computed tomography),
      metaiodobenzylguanidine scintigraphy, and/or core needle biopsy. RESULTS: The
      male/female ratio was 1.4:1.0. Median tumor size at presentation was 29 mm (range
      10-50 mm). Eight lesions were detected antenatally. Ten lesions were diagnosed as
      localized neuroblastoma. Of these ten lesions, four were excised because of
      parental preference (n = 2), tumor enlargement (n = 1) or tumor persistence (n =
      1). The remaining six patients underwent watchful clinical observation, which
      showed progressive tumor shrinkage and complete regression within 10-39 months
      (median 12.5 months). The final two lesions were small predominantly cystic
      lesions without a clear-cut diagnosis. They were managed noninvasively. At an
      overall median follow-up of 109 months (range 30-122 months), all patients are
      alive and disease-free, although one patient progressed to stage 4 disease
      despite early excision of the primary tumor. CONCLUSIONS: Spontaneous regression
      of localized perinatal adrenal neuroblastoma occurs often, and a "wait and see"
      strategy seems justified in these small infants. Patients with enlarging or
      stable lesions that have persisted for several months may benefit from surgery,
      although prompt excision may not prevent tumor progression.

PMID- 23135424
TI  - Experience with recurrent respiratory papillomatosis in a developing country:
      impact of tracheostomy.
AB  - BACKGROUND: The frequent relapses of recurrent respiratory papillomatosis (RRP)
      sometimes demand repeated surgical excision with tracheostomy. This situation
      plays a vital role in the management of RRP in developing countries such as ours
      because of late presentation. This study was conducted to evaluate our experience
      with RRP and to determine the incidence and impact of tracheostomy in the overall
      management and outcomes of our patients. METHODS: The records of 59 patients with
      histologically confirmed RRP treated between 1994 and 2008 at our tertiary
      institution were reviewed. We collected data such as age at onset, tracheostomy
      frequency and duration, number of required surgical excisions, papilloma spread
      to the lower airways. Patients' characteristics and the course of the disease
      were compared between a juvenile-onset papillomatosis (JoRRP) group and an adult
      onset group (AdRRP). RESULTS: Overall, 68 % of our patients were in the JoRRP
      group (ages 2-11 years, mean 6 years). The other 32 % were 22-58 years of age
      (AdRRP group). Two cases of JoRRP continued into adult life. Multiple RRP
      dominated in the JoRRP group (93 %), whereas solitary papillomas predominated in
      the AdRRP group (63 %). Tracheostomy was performed because of upper airway
      obstruction in 42 % of our patients, with children accounting for 72 %. The mean
      duration of tracheostomy was 3.5 months, with 80 % lasting <4 months.
      Significantly more JoRRP patients had severe upper airway obstruction, required
      tracheostomy, and underwent multiple surgical excisions (p = 0.04, 0.02, and
      0.009, respectively). Tracheobronchial spread occurred in a patient with
      prolonged tracheostomy. CONCLUSIONS: Multiple laryngeal papillomatosis clearly
      followed a more severe and less predictable course than the solitary type in both
      groups. Although there was a high incidence of tracheostomy in this study, short
      duration tracheostomies accounted for the low incidence of extralaryngeal spread.

PMID- 23135425
TI  - Chair-side generated posterior lithium disilicate crowns after 4 years.
AB  - OBJECTIVES: The objective of this prospective clinical study was to evaluate the
      performance of chair-side generated crowns after 48 months. MATERIALS AND
      METHODS: Forty-one posterior full contour crowns made of a machinable lithium
      disilicate ceramic (e.max CAD LT) were inserted in 34 patients applying a chair
      side CAD/CAM technique. One crown per patient was randomly selected for
      evaluation at baseline, after 6, 12, 24, 36, and 48 months according to modified
      US Public Health Service criteria. RESULTS: After a mean observation time of 51
      months (min, 48 months; max, 56 months; SD +/- 2.3 months), 29 crowns were
      available for re-examination. Within the observation period, one failure occurred
      due to a crown fracture after 2.8 years. Four abutment teeth revealed signs of
      biological complications: Two abutment changed sensibility perception from
      positive to negative within the first 13 month. Two abutment teeth showed
      secondary caries below the crown margin, one after the 24, and another after the
      48 month recall. Both abutments received cervical adhesive composite fillings.
      The failure-free rate was 96.3 % after 4 years according to Kaplan-Meier (CI:
      upper bound, 4.4 years; lower bound, 4.7 years). CONCLUSIONS: Due to the fact
      that the secondary caries was not caused as a result of an inaccuracy of the
      crown margins and the endodontic complications were in a normal range, the
      clinical performance of the crowns was completely satisfying. CLINICAL RELEVANCE:
      The chair-side application of lithium disilicate crowns can be recommended.

PMID- 23135426
TI  - Oral health care utilization in children with disabilities.
AB  - OBJECTIVES: The objectives of this report were to survey the utilization of oral
      health care in children and adolescents with disabilities over a 7-year period
      and to compare these data with the utilization pattern of their peers without
      disabilities. For most countries, these data have not been published in the
      international literature so far. MATERIAL AND METHODS: The cohort used was the
      Permanent Sample of Socially Insured Persons, an anonymous representative sample
      of Belgian residents. The database comprised prospective data on oral and general
      health care utilization and sociodemographic variables collected from 2002 up to
      2008. RESULTS: Data were available from 326 children and adolescents with and
      53,589 without disabilities. Dental attendance rates were low in both subgroups:
      only 50 % had a dental visit in four or more of the seven observation years.
      Emergency oral and medical care was recorded significantly more often in children
      with disabilities whereas radiographs, restorations, and orthodontic assessments
      and treatments more frequently in children without disabilities. CONCLUSION: The
      present study demonstrated that dental attendance rates in both subgroups were
      low and that in those who attended, preventive oral health care was only
      infrequently attested. Further research is needed to elucidate whether the lower
      number of radiographs and restorations and the higher number of emergency visits
      observed in the subgroup with disabilities reflect unmet oral treatment needs.
      CLINICAL RELEVANCE: Objective data on health care utilization are essential to
      enable governments and stakeholders to devise appropriate care and to optimize
      access to care for persons with disabilities.

PMID- 23135427
TI  - Salivary bacteria and oral health status in medicated and non-medicated children
      and adolescents with attention deficit hyperactivity disorder (ADHD).
AB  - OBJECTIVES: Attention deficit hyperactivity disorder (ADHD) is a childhood
      neurological disorder. Studies have shown that children with ADHD are more prone
      to caries than those without. The study investigated children diagnosed with
      ADHD, both with and without pharmacological intervention, and the following:
      DMFT?dmft, plaque index (PI), mutans streptococci (MS) levels, lactobacilli (LB)
      levels, salivary flow, salivary buffer capacity, oral hygiene, and diet. STUDY
      DESIGN: DMFT/dmft index, PI, MS and LB levels, salivary flow, and salivary buffer
      capacity were examined in three groups of children: ADHD1-diagnosed with ADHD
      with no pharmacological intervention (N = 31), ADHD2-treated with medications for
      ADHD (N = 30), and a healthy control group (N = 30). Diet and oral health habits
      were assessed through questionnaires completed by parents. RESULTS: There were no
      differences in the DMFT/dmft index, MS and LB counts, salivary buffer capacity,
      and parent reported diet and oral health behavior between the three groups.
      Children with ADHD demonstrated a higher plaque index. CONCLUSIONS: Although
      children with ADHD did not report different diet and oral health behavior from
      children without ADHD, this group had significantly higher levels of plaque than
      the control group, which combined with hyposalivation may be a risk factor for
      caries at an older age. CLINICAL RELEVANCE: Medicated and non-medicated ADHD
      children were similar to control children in their caries rate, MS and LB counts,
      salivary buffer capacity, and diet and oral health behavior. They differed in the
      amount of plaque found on their teeth. As a group, ADHD children demonstrated
      hyposalivation compared with the control.

PMID- 23135428
TI  - Switching the activity of a photoredox catalyst through reversible encapsulation
      and release.
AB  - Reversible encapsulation of [Ru(bpy)(3)](2+) within a self-assembled hexameric
      resorcin[4]arene capsule turns off the photocatalytic aerobic oxidation of an
      aliphatic sulfide. Upon addition of a competitive cationic guest, the Ru(II)
      catalyst is released into solution where its catalytic activity is restored.

PMID- 23135429
TI  - China's new leaders must keep science in focus.

PMID- 23135440
TI  - Hurricane sweeps US into climate-adaptation debate.

PMID- 23135441
TI  - Researchers battle storm's wrath.

PMID- 23135442
TI  - Laser lab shifts focus to warheads.

PMID- 23135444
TI  - Space telescope to get software fix.

PMID- 23135443
TI  - One-stop shop for disease genes.

PMID- 23135445
TI  - Irish science adviser office axed.

PMID- 23135446
TI  - Hopes linger for Mars methane.

PMID- 23135447
TI  - Education: Africa's counting house.

PMID- 23135448
TI  - Melting in the Andes: Goodbye glaciers.

PMID- 23135449
TI  - Autoimmunity: The worm returns.

PMID- 23135450
TI  - Centenary: The birth of X-ray crystallography.

PMID- 23135456
TI  - L'Aquila: science is not a crystal ball.

PMID- 23135457
TI  - L'Aquila: governance flaws exposed.

PMID- 23135458
TI  - Publishing: Europe on the rise in Science and Nature.

PMID- 23135459
TI  - Higher education: Call for a European integrity standard.

PMID- 23135460
TI  - Reporting standards: Rigid guidelines may restrict research.

PMID- 23135461
TI  - Keith H. Campbell (1954-2012).

PMID- 23135463
TI  - Imaging: The fog clears.

PMID- 23135462
TI  - Translational medicine: Mice and men show the way.

PMID- 23135464
TI  - Applied physics: Brighter images with no added noise.

PMID- 23135466
TI  - Structural biology: A toolbox for protein design.

PMID- 23135467
TI  - Principles for designing ideal protein structures.
AB  - Unlike random heteropolymers, natural proteins fold into unique ordered
      structures. Understanding how these are encoded in amino-acid sequences is
      complicated by energetically unfavourable non-ideal features--for example kinked
      alpha-helices, bulged beta-strands, strained loops and buried polar groups--that
      arise in proteins from evolutionary selection for biological function or from
      neutral drift. Here we describe an approach to designing ideal protein structures
      stabilized by completely consistent local and non-local interactions. The
      approach is based on a set of rules relating secondary structure patterns to
      protein tertiary motifs, which make possible the design of funnel-shaped protein
      folding energy landscapes leading into the target folded state. Guided by these
      rules, we designed sequences predicted to fold into ideal protein structures
      consisting of alpha-helices, beta-strands and minimal loops. Designs for five
      different topologies were found to be monomeric and very stable and to adopt
      structures in solution nearly identical to the computational models. These
      results illuminate how the folding funnels of natural proteins arise and provide
      the foundation for engineering a new generation of functional proteins free from
      natural evolution.

PMID- 23135468
TI  - Non-invasive imaging through opaque scattering layers.
AB  - Non-invasive optical imaging techniques, such as optical coherence tomography,
      are essential diagnostic tools in many disciplines, from the life sciences to
      nanotechnology. However, present methods are not able to image through opaque
      layers that scatter all the incident light. Even a very thin layer of a
      scattering material can appear opaque and hide any objects behind it. Although
      great progress has been made recently with methods such as ghost imaging and
      wavefront shaping, present procedures are still invasive because they require
      either a detector or a nonlinear material to be placed behind the scattering
      layer. Here we report an optical method that allows non-invasive imaging of a
      fluorescent object that is completely hidden behind an opaque scattering layer.
      We illuminate the object with laser light that has passed through the scattering
      layer. We scan the angle of incidence of the laser beam and detect the total
      fluorescence of the object from the front. From the detected signal, we obtain
      the image of the hidden object using an iterative algorithm. As a proof of
      concept, we retrieve a detailed image of a fluorescent object, comparable in size
      (50 micrometres) to a typical human cell, hidden 6 millimetres behind an opaque
      optical diffuser, and an image of a complex biological sample enclosed between
      two opaque screens. This approach to non-invasive imaging through strongly
      scattering media can be generalized to other contrast mechanisms and geometries.

PMID- 23135469
TI  - Integration of chemical catalysis with extractive fermentation to produce fuels.
AB  - Nearly one hundred years ago, the fermentative production of acetone by
      Clostridium acetobutylicum provided a crucial alternative source of this solvent
      for manufacture of the explosive cordite. Today there is a resurgence of interest
      in solventogenic Clostridium species to produce n-butanol and ethanol for use as
      renewable alternative transportation fuels. Acetone, a product of acetone-n
      butanol-ethanol (ABE) fermentation, harbours a nucleophilic alpha-carbon, which
      is amenable to C-C bond formation with the electrophilic alcohols produced in ABE
      fermentation. This functionality can be used to form higher-molecular-mass
      hydrocarbons similar to those found in current jet and diesel fuels. Here we
      describe the integration of biological and chemocatalytic routes to convert ABE
      fermentation products efficiently into ketones by a palladium-catalysed
      alkylation. Tuning of the reaction conditions permits the production of either
      petrol or jet and diesel precursors. Glyceryl tributyrate was used for the in
      situ selective extraction of both acetone and alcohols to enable the simple
      integration of ABE fermentation and chemical catalysis, while reducing the energy
      demand of the overall process. This process provides a means to selectively
      produce petrol, jet and diesel blend stocks from lignocellulosic and cane sugars
      at yields near their theoretical maxima.

PMID- 23135470
TI  - Greenland ice-sheet contribution to sea-level rise buffered by meltwater storage
      in firn.
AB  - Surface melt on the Greenland ice sheet has shown increasing trends in areal
      extent and duration since the beginning of the satellite era. Records for melt
      were broken in 2005, 2007, 2010 and 2012. Much of the increased surface melt is
      occurring in the percolation zone, a region of the accumulation area that is
      perennially covered by snow and firn (partly compacted snow). The fate of melt
      water in the percolation zone is poorly constrained: some may travel away from
      its point of origin and eventually influence the ice sheet's flow dynamics and
      mass balance and the global sea level, whereas some may simply infiltrate into
      cold snow or firn and refreeze with none of these effects. Here we quantify the
      existing water storage capacity of the percolation zone of the Greenland ice
      sheet and show the potential for hundreds of gigatonnes of meltwater storage. We
      collected in situ observations of firn structure and meltwater retention along a
      roughly 85-kilometre-long transect of the melting accumulation area. Our data
      show that repeated infiltration events in which melt water penetrates deeply
      (more than 10 metres) eventually fill all pore space with water. As future
      surface melt intensifies under Arctic warming, a fraction of melt water that
      would otherwise contribute to sea-level rise will fill existing pore space of the
      percolation zone. We estimate the lower and upper bounds of this storage sink to
      be 322 +/- 44 gigatonnes and  1,289(+388)(-252) gigatonnes, respectively.
      Furthermore, we find that decades are required to fill this pore space under a
      range of plausible future climate conditions. Hence, routing of surface melt
      water into filling the pore space of the firn column will delay expansion of the
      area contributing to sea-level rise, although once the pore space is filled it
      cannot quickly be regenerated.

PMID- 23135471
TI  - Mechanisms for oscillatory true polar wander.
AB  - Palaeomagnetic studies of Palaeoproterozoic to Cretaceous rocks propose a suite
      of large and relatively rapid (tens of degrees over 10 to 100 million years)
      excursions of the rotation pole relative to the surface geography, or true polar
      wander (TPW). These excursions may be linked in an oscillatory, approximately
      coaxial succession about the centre of the contemporaneous supercontinent. Within
      the framework of a standard rotational theory, in which a delayed viscous
      adjustment of the rotational bulge acts to stabilize the rotation axis,
      geodynamic models for oscillatory TPW generally appeal to consecutive, opposite
      loading phases of comparable magnitude. Here we extend a nonlinear rotational
      stability theory to incorporate the stabilizing effect of TPW-induced elastic
      stresses in the lithosphere. We demonstrate that convectively driven inertia
      perturbations acting on a nearly prolate, non-hydrostatic Earth with an effective
      elastic lithospheric thickness of about 10 kilometres yield oscillatory TPW paths
      consistent with palaeomagnetic inferences. This estimate of elastic thickness can
      be reduced, even to zero, if the rotation axis is stabilized by long-term excess
      ellipticity in the plane of the TPW. We speculate that these sources of
      stabilization, acting on TPW driven by a time-varying mantle flow field, provide
      a mechanism for linking the distinct, oscillatory TPW events of the past few
      billion years.

PMID- 23135473
TI  - Expression and the clinical significance of Wnt10a and Wnt10b in endometrial
      cancer are associated with the Wnt/beta-catenin pathway.
AB  - To determine the role played by the Wnt/beta-catenin signaling pathway in the
      development of endometrial cancer (EC), we examined the expression of Wnt10a and
      Wnt10b in EC tissues and the correlation between their expression. Furthermore,
      the associations between these two proteins and the clinicopathological
      characteristics and prognosis of EC were also evaluated. In our search of
      alternative mechanisms, we investigated the impact of Wnt10b on proliferation and
      apoptosis of EC cells. Western blotting, 3-(4, 5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay and flow cytometry were used to evaluate
      the expression of Wnt10b and some key proteins of the Wnt/beta-catenin pathway,
      proliferation and apoptosis in EC. Our results showed that Wnt10b expression in
      EC tissues was significantly higher compared to that in hyperplastic and normal
      samples. The expression of Wnt10a in endometrioid cancer tissues was higher
      compared to that in other types of cancerous samples. The difference in Wnt10b
      levels was significant among subgroups for histological type, grade of
      differentiation, FIGO phase and lymphovascular metastasis. Furthermore, no
      correlation was observed between the expression of Wnt10a and Wnt10b. In the
      follow-up, Wnt10b gene expression was frequently upregulated in EC and associated
      with better prognostic clinicopathological markers in EC patients. Collectively,
      the in vitro data showed that the upregulated expression of Wnt10b in Ishikawa
      cells promoted proliferation and inhibited apoptosis through beta-catenin and c
      myc activation and adenomatous polyposis coli (APC) inhibition, which suggests
      that Wnt10b activates EC via the Wnt/beta-catenin pathway. These results suggest
      that Wnt10b likely plays an important role in the development of EC. Furthermore,
      these results identify a role for Wnt10b in EC cells through promoting
      proliferation and inhibiting apoptosis, primarily through the activation of the
      Wnt/beta-catenin pathway. The role played by Wnt10a in EC, however, still
      requires further investigation.

PMID- 23135475
TI  - Hierarchical composition of the axial filament from spicules of the siliceous
      sponge Suberites domuncula: from biosilica-synthesizing nanofibrils to structure-
      and morphology-guiding triangular stems.
AB  - The major structural and enzymatically active protein in spicules from siliceous
      sponges, e.g., for Suberites domuncula studied here, is silicatein. Silicatein
      has been established to be the key enzyme that catalyzes the formation of
      biosilica, a polymer that represents the inorganic scaffold for the spicule. In
      the present study, it is shown, by application of high-resolution transmission
      and scanning transmission electron microscopy that, during the initial phase of
      spicule synthesis, nanofibrils with a diameter of around 10 nm are formed that
      comprise bundles of between 10 and 20 nanofibrils. In intracellular vacuoles,
      silicasomes, the nanofibrils form polar structures with a pointed tip and a blunt
      end. In a time-dependent manner, these nanofibrillar bundles become embedded into
      a Si-rich matrix, indicative for the formation of biosilica via silicatein
      molecules that form the nanofibrils. These biosilicified nanofibrillar bundles
      become extruded from the intracellular space, where they are located in the
      silicasomes, to the extracellular environment by an evagination process, during
      which a cellular protrusion forms the axial canal in the growing spicule. The
      nanofibrillar bundles condense and progressively form the axial filament that
      becomes localized in the extracellular space. It is concluded that the silicatein
      composing nanofibrils act not only as enzymatic silica bio-condensing platforms
      but also as a structure-giving guidance for the growing spicule.

PMID- 23135476
TI  - MicroRNAs as markers for neurally committed CD133+/CD34+ stem cells derived from
      human umbilical cord blood.
AB  - Neural differentiation of the CD133+/CD34+ subpopulation of human umbilical cord
      blood stem cells was investigated, and neuro-miR (mir-9 and mir-124) expression
      was examined. An efficient induction protocol for neural differentiation of
      hematopoietic stem cells together with the exclusion of retinoic acid in this
      process was also studied. Transcription of some neural markers such as
      microtubule-associated protein-2, beta-tubulin III, and neuron-specific enolase
      was evaluated by real-time PCR, immunocytochemistry, and western blotting.
      Increased expression of neural indicators in the treated cells confirmed the
      appropriate neural differentiation, which supported the high efficiency of our
      defined neuronal induction protocol. Verified high expression of neuro-miRNAs
      along with neuronal specific proteins not only strengthens the regulatory role of
      miRNAs in determining stem cell fate but also introduces these miRNAs as novel
      indicators of neural differentiation. These data highlight the prominent
      therapeutic potential of hematopoietic stem cells for use in cell therapy of
      neurodegenerative diseases.

PMID- 23135477
TI  - The enzymes of beta-lactam biosynthesis.
AB  - The beta-lactam antibiotics and related beta-lactamase inhibitors are amongst the
      most important small molecules in clinical use. Most, but not all, beta-lactams
      including penicillins, cephalosporins, and clavulanic acid are produced via
      fermentation or via modification of fermented intermediates, with important
      exceptions being the carbapenems and aztreonam. The desire for more efficient
      routes to existing antibiotics and for access to new and synthetically
      challenging ones stimulates continued interest in beta-lactam biosynthesis. We
      review knowledge of the pathways leading to beta-lactam antibiotics focusing on
      the mechanisms, structures and biocatalytic applications of the enzymes involved.

PMID- 23135478
TI  - Epithelial-mesenchymal transition-related gene expression as a new prognostic
      marker for neuroblastoma.
AB  - Neuroblastoma (NB) is a highly metastatic tumor in children. The epithelial
      mesenchymal transition (EMT) is an important mechanism for both the initiation of
      tumor invasion and subsequent metastasis. This study investigated the role of EMT
      in the progression of NB. Using EMT assays on samples from 11 tumors, we
      identified 14 genes that were either differentially expressed between tumors of
      different stages or highly upregulated in NB. Quantitative RT-PCR of these genes
      was conducted in 96 NB tumors and their expression levels were compared between
      stages and between tumors with the presence and absence of MYCN amplification.
      The association of survival rate with differential gene expression was
      investigated. Expression of KRT19 was significantly decreased in stage 3 or 4 NB
      as well as stage 4S NB compared with stage 1 or 2 NB. Expression levels of KRT19
      and ERBB3 were significantly low, and expression levels of TWST1 and TCF3 were
      high in MYCN-amplified NB. The patients with low expression of KRT19 or ERBB3
      showed significantly worse overall survival. Furthermore, the correlation between
      high invasive ability and low expression of KRT19 and ERBB3 was suggested in
      vitro using six NB cell lines. The authors conclude that downregulation of KRT19
      is highly associated with tumor progression in NB and metastasis in localized
      primary NB and that low expression of ERBB3 is also associated with progression
      of NB.

PMID- 23135479
TI  - Blastic plasmacytoid dendritic cell neoplasm: a single-center experience.
AB  - Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive hematologic
      malignancy originating from the precursor of the plasmacytoid dendritic cell. It
      is very rare and has only recently been recognized as a distinct entity. In this
      study, we report our experience of BPDCN to review the clinical, pathological
      features and treatment outcomes. A database at the Asan Medical Center was
      screened for all patients with BPDCN treated between 2000 and 2010. Seven
      patients were confirmed as BPDCN and included in this analysis. The median age of
      the patients was 40 years (range, 18-62 years), and four patients were male.
      Sites of disease involvement included the skin (n = 4), lymph node (n = 4), and
      peripheral blood/bone marrow (n = 2). Tumor cells were positive for CD4 (n = 5),
      CD56 (n = 6), and CD123 (n = 7). Six patients received multi-agent chemotherapy
      as first-line treatment, while one patient was given radiotherapy. The median
      progression-free survival was 8.6 months (range, 2.6-28.9 months) and overall
      survival was 15.1 months (range, 4.4-60.0 months) with a median follow-up period
      of 13.8 months (range, 1.9-29.9 months). Notably, all four patients with
      cutaneous involvement survived, whereas those without skin involvement succumbed
      to death, even though two of them were given salvage chemotherapy. In this study,
      patients with BPDCN showed various clinical, histological, and immunophenotypical
      features. Our experience warrants further examination of the prognostic
      significance of skin involvement in BPDCN.

PMID- 23135480
TI  - Critical roles of RNA-binding proteins in miRNA biogenesis in Arabidopsis.
AB  - MicroRNAs (miRNAs) are key regulators of gene expression and play critical roles
      in modulating metabolism, development and physiology in animals and plants. miRNA
      levels are transcriptionally and post-transcriptionally controlled for their
      proper function. Recent studies have shown that RNA-binding proteins play
      important roles in producing miRNAs by affecting the accurate and/or efficient
      processing of precursors of miRNAs. Many of these RNA-binding proteins also have
      roles in general RNA metabolism, indicating potential connections between miRNA
      biogenesis and other RNA metabolism. Here, we focus on the function of several
      RNA-binding proteins in miRNA biogenesis in Arabidopsis.

PMID- 23135481
TI  - Novel polyoxometalate-phosphazene aggregates and their use as catalysts for
      biphasic oxidations with hydrogen peroxide.
AB  - Polyoxometalate-phosphazene salt aggregates comprising cyclophosphazene cations
      are highly efficient catalysts for environmentally benign biphasic oxidations
      with hydrogen peroxide. These catalysts self-assemble in situ simply by mixing
      commercial Keggin POMs and readily available phosphazenes.

PMID- 23135482
TI  - Protozoa and human macrophages infection by Legionella pneumophila environmental
      strains belonging to different serogroups.
AB  - Three Legionella pneumophila strains isolated from municipal hot tap water during
      a multicentric Italian survey and belonging to serogroups 1, 6, 9 and the
      reference strain Philadelphia-1 were studied to determine the intracellular
      replication capability and the cytopathogenicity in human monocyte cell line U937
      and in an Acanthamoeba polyphaga strain. Our results show that both serogroups 1
      and Philadelphia-1 were able to multiply into macrophages inducing
      cytopathogenicity, while serogroup 6 and ever more serogroup 9 were less
      efficient in leading to death of the infected macrophages. Both serogroups 1 and
      6 displayed a quite good capability of intracellular replication in A. polyphaga,
      although serogroup 1 was less cytopathogenic than serogroup 6. Serogroup 9, like
      Philadelphia-1 strain, showed a reduced efficiency of infection and replication
      and a low cytopathogenicity towards the protozoan. Our study suggests that
      bacterial pathogenesis is linked to the difference in the virulence expression of
      L. pneumophila serogroups in both hosts, as demonstrated by the fact that only L.
      pneumophila serogroup 1 shows the contextual expression of the two virulence
      traits. Serogroup 6 proves to be a good candidate as pathogen since it shows a
      good capacity for intracellular replication in protozoan.

PMID- 23135483
TI  - Use of biological prostheses in transplant patients with incisional hernias.
      Preliminary experience.
AB  - AIM: The use of synthetic mesh in transplant patients is still under debate. In
      this paper the authors report their preliminary experience on biological
      prosthesis for surgical treatment of incisional hernias in transplant patients.
      MATERIAL OF STUDY: Between 2009-2010, 10 patients with incisional hernia
      underwent surgery using a biological prosthesis (porcine dermis collagen). All
      patients were transplanted: 9 kidney transplants and 1 liver transplant. RESULTS:
      In all patients postoperative course was uneventful and were not observed
      complications related to surgery, kind of prosthesis or transplanted organs. At
      follow up, laparoplasty was associated with good functional outcome. DISCUSSION:
      Transplant patients are at risk for use of synthetic prostheses, as
      immunosuppressed. In our preliminary experience biological prostheses compared to
      synthetic ones showed a greater ability to integrate into tissues, to resist
      bacterial colonization and to reduce cytotoxic or allergenic reactions, providing
      similar functional results. Moreover it must be added that biological prostheses
      did not require reductions/suspensions of immunosuppressive therapy and resulted
      to be versatile. All these features are particularly sought in incisional hernias
      surgery of transplanted patients. CONCLUSIONS: Surgery of incisional hernias in
      transplanted patients requires a prosthesis with characteristics as close as
      possible to the ideal one and, in this sense, biological prostheses would seem to
      outweigh synthetic ones. In our experience, biological prostheses have shown to
      be safe, effective and reliable; therefore they seem to be able to open new
      horizons in the treatment of wall defects in this group of patients.

PMID- 23135484
TI  - Graphene oxide as a multi-functional p-dopant of transparent single-walled carbon
      nanotube films for optoelectronic devices.
AB  - Modulation of electronic structures and surface properties of transparent carbon
      nanotube films is a challenging issue for their application in optoelectronic
      devices. Here, we report, for the first time, that graphene oxide (GO) nanosheets
      play the role of a p-doping agent and surface energy modifier of single-walled
      carbon nanotube (SWCNT)-based transparent conducting electrodes (TCEs). The
      deposition of highly oxidized, small-sized (i.e., diameter of less than 500 nm)
      GO nanosheets onto a SWCNT network film reduces the sheet resistance of the
      pristine film to 60% of its original value by p-doping. The modified TCEs exhibit
      an outstanding optoelectronic feature of high conductivity with high
      transparency. Moreover, the wettability of the electrode surface was also
      noticeably increased, which is advantageous for the solution-based processing of
      organic electronics. Furthermore, the organic photovoltaic (OPV) cells with the
      GO-doped SWCNT anodes on flexible substrates were successfully demonstrated. In
      stark contrast to a power conversion efficiency of 0.44% for pristine SWCNT
      anodes, GO-doped SWCNT anodes show a drastically enhanced power conversion
      efficiency of 2.7%.

PMID- 23135487
TI  - Facile one-pot synthesis of uniform TiO2-Ag hybrid hollow spheres with enhanced
      photocatalytic activity.
AB  - TiO(2)-Ag hybrid hollow spheres (about 700 nm in diameter) with a highly uniform
      morphology and good structural stability were facilely prepared via a one-pot
      hydrothermal method, using carbon spheres as templates followed by an annealing
      treatment. Through this route, the as-prepared hybrid hollow spheres preserved
      the uniformity of the initial carbon sphere templates and the loading amount of
      the Ag nanocrystals can be conveniently varied or controlled by the concentration
      of the Ag precursor. The investigation of the photocatalytic ability demonstrated
      that the as-prepared TiO(2)-Ag hybrid hollow spheres possess excellent
      photocatalytic activity, superior to commercial TiO(2) nanoparticles (Degussa
      P25), for the degradation of rhodamine B (RhB) and methyl orange (MO) dyes under
      visible-light illumination. Furthermore, the OH radicals formed during
      photocatalysis with different Ag content hybrids were revealed by means of a
      terephthalic acid fluorescence probe method, which uncovers that the Ag content
      in the TiO(2)-Ag hybrids was crucial to obtain an optimal synergistic effect
      between the Ag and TiO(2) for the degradation of organic pollutants. Accordingly,
      the optimum matching for the best photocatalytic activity was investigated
      thoroughly and a reasonable mechanism was also proposed.

PMID- 23135488
TI  - Hexavalent chromium reduction by Cellulomonas sp. strain ES6: the influence of
      carbon source, iron minerals, and electron shuttling compounds.
AB  - The reduction of hexavalent chromium, Cr(VI), to trivalent chromium, Cr(III), can
      be an important aspect of remediation processes at contaminated sites.
      Cellulomonas species are found at several Cr(VI) contaminated and uncontaminated
      locations at the Department of Energy site in Hanford, Washington. Members of
      this genus have demonstrated the ability to effectively reduce Cr(VI) to Cr(III)
      fermentatively and therefore play a potential role in Cr(VI) remediation at this
      site. Batch studies were conducted with Cellulomonas sp. strain ES6 to assess the
      influence of various carbon sources, iron minerals, and electron shuttling
      compounds on Cr(VI) reduction rates as these chemical species are likely to be
      present in, or added to, the environment during in situ bioremediation. Results
      indicated that the type of carbon source as well as the type of electron shuttle
      present influenced Cr(VI) reduction rates. Molasses stimulated Cr(VI) reduction
      more effectively than pure sucrose, presumably due to presence of more easily
      utilizable sugars, electron shuttling compounds or compounds with direct Cr(VI)
      reduction capabilities. Cr(VI) reduction rates increased with increasing
      concentration of anthraquinone-2,6-disulfonate (AQDS) regardless of the carbon
      source. The presence of iron minerals and their concentrations did not
      significantly influence Cr(VI) reduction rates. However, strain ES6 or AQDS could
      directly reduce surface-associated Fe(III) to Fe(II), which was capable of
      reducing Cr(VI) at a near instantaneous rate. These results suggest the rate
      limiting step in these systems was the transfer of electrons from strain ES6 to
      the intermediate or terminal electron acceptor whether that was Cr(VI), Fe(III),
      or AQDS.

PMID- 23135489
TI  - Casticin, a flavonoid, potentiates TRAIL-induced apoptosis through modulation of
      anti-apoptotic proteins and death receptor 5 in colon cancer cells.
AB  - We investigated the effect of casticin on apoptosis induced by tumor necrosis
      factor (TNF)-related apoptosis-inducing ligand (TRAIL). We found that casticin
      potentiated TRAIL-induced apoptosis in human colon cancer cells. Casticin
      downregulated cell survival proteins including Bcl-xL, Bcl-2, survivin, XIAP and
      cFLIP, and induced death receptor 5 (DR5), but had no effect on DR4 and decoy
      receptors (DcR1 or DcR2). Deletion of DR5 by siRNA significantly reduced the
      apoptosis induced by TRAIL and casticin. In addition, casticin induced reactive
      oxygen species (ROS) generation in a dose-dependent manner. Collectively, the
      present study showed that casticin potentiates TRAIL-induced apoptosis through
      downregulation of cell survival proteins and induction of DR5 mediated by ROS.

PMID- 23135490
TI  - Microbial transformation and sorption of anthracene in liquid culture.
AB  - Armillaria sp. F022, a white-rot fungus isolated from decayed wood in tropical
      rain forest was used to biodegrade anthracene in cultured medium. The percentage
      of anthracene removal by Armillaria sp. F022 reached 13 % after 7 days and at the
      end of the experiment, anthracene removal level was at 87 %. The anthracene
      removal through sorption and transformation was investigated. 69 % of eliminated
      anthracene was transformed by Armillaria sp. F022 to form other organic
      structure, while only 18 % was absorbed in the mycelia. In the kinetic
      experiment, anthracene dissipation will not stop even though the biomass had
      stopped growing. Anthracene removal by Armillaria sp. F022 was correlated with
      protein concentration (whole biomass) in the culture. The production of enzyme
      was affected by biomass production. Anthracene was transformed to two stable
      metabolic products. The metabolites were extracted in ethyl-acetate, isolated by
      column chromatography, and then identified using gas chromatography-mass
      spectrometry (GC-MS). 

PMID- 23135491
TI  - Mathematical modelling and process optimization of a continuous 5-stage
      bioreactor cascade for production of poly[-(R)-3-hydroxybutyrate] by Cupriavidus
      necator.
AB  - A multistage system for poly(hydroxyalkanoate) (PHA) production consisting of
      five continuous stirred tank reactors in series (5-CSTR) with Cupriavidus necator
      DSM 545 as production strain was modelled using formal kinetic relations.
      Partially growth-associated production of PHA under nitrogen limited growth was
      chosen as modelling strategy, thus the Luedeking-Piret's model of partial growth
      associated product synthesis was applied as working hypothesis. Specific growth
      rate relations adjusted for double substrate (C and N source) limited growth
      according to Megee et al. and Mankad-Bungay relation were tested. The first stage
      of the reactor cascade was modelled according to the principle of nutrient
      balanced continuous biomass production system, the second one as two substrate
      controlled process, while the three subsequent reactors were adjusted to produce
      PHB under continuous C source fed and nitrogen deficiency. Simulated results of
      production obtained by the applied mathematical models and computational
      optimization indicate that PHB productivity of the whole system could be
      significantly increased (from experimentally achieved 2.14 g L(-1) h(-1) to
      simulated 9.95 g L(-1) h(-1)) if certain experimental conditions would have been
      applied (overall dilution rate, C and N source feed concentration). Additionally,
      supplemental feeding strategy for switching from batch to continuous mode of
      cultivation was proposed to avoid substrate inhibition. 

PMID- 23135492
TI  - Chemo-enzymatic asymmetric synthesis of S-citalopram by lipase-catalyzed cyclic
      resolution and stereoinversion of quaternary stereogenic center.
AB  - A chemo-enzymatic synthesis method of S-citalopram was developed to overcome the
      disadvantage of relatively low selectivity of enzyme towards tertiary alcohols.
      The combination of kinetic resolution, cyclic resolution and stereoinversion
      synthesis was successfully applied in the asymmetric synthesis of the S
      citalopram. Using the kinetic model to predict the cyclic resolution, R-diol with
      high ee value was obtained by controlling the conversion rate. Subsequently, the
      unwanted R-diol was inverted to S-citalopram by stereoinversion of chiral
      quaternary center with 98.0% yield and ee value of 91.0%. Based on dynamic
      simulation and experiments, the kinetic resolution was scaled up from 10 mL to 1
      L and 14 L, gradually. There was no significant scale-up effect and the dynamic
      simulation result fitted the experimental data well, with an error of 12.5 and
      14.0%, respectively. This chemo-enzymatic synthesis route is a promising model
      system for the production of pharmaceuticals with the chiral tertiary alcohols
      intermediate.

PMID- 23135493
TI  - Toward clinical transparency.

PMID- 23135494
TI  - Prisoners, hard hit by hepatitis C, decry lack of access to drugs.

PMID- 23135496
TI  - Europe plays catch-up on neonatal screening as US skips ahead.

PMID- 23135497
TI  - Targeted vaccines against feline dander could be the cat's meow.

PMID- 23135501
TI  - Straight talk with...David Baker.
AB  - Thirty years ago, technology companies began nestling their facilities close to
      academia, and the idea of the university research park was born. Soon after, the
      concept took off in the field of medicine, and today it's not hard to find such
      innovation hubs that house biomedical startups drawing on the brainpower of
      professors and students alike. In late September, the Tucson, Arizona-based
      Association of University Research Parks--which includes about 170 research parks
      -announced that David Baker would serve as president of the organization's board
      of directors for the next year and help guide its strategic goals for the next
      five years. Baker, who is also the executive director of the University
      Technology Park at the Illinois Institute of Technology in Chicago, spoke with
      Roxanne Khamsi about how the organization hopes to branch out and transform these
      workplaces.

PMID- 23135503
TI  - Call in the backup.

PMID- 23135505
TI  - Clinical trials must cope better with multiplicity.
AB  - Clinical trials typically address more than one question. But in attempting to
      protect against misleading results that are due to chance when multiple
      interrelated tests are run simultaneously, researchers sometimes apply overly
      strict statistical devices that mask true effects. They should give more
      consideration to choosing the type of statistical analysis that fits best.

PMID- 23135507
TI  - Not just a rush of blood to the head.
AB  - Angiogenesis is a key feature of central nervous system injury. A neovessel
      derived signal mediated by prostacyclin triggers axonal sprouting and functional
      recovery in a mouse model of inflammatory spinal cord injury (pages 1658-1664).
      Are such angiocrine signals relevant to neurovascular remodeling and recovery in
      other neurological contexts?

PMID- 23135508
TI  - SAMHD1 does it again, now in resting T cells.
AB  - A long-standing question in the HIV field is why HIV-1 fails to replicate in
      resting CD4(+) T cells. A new study shows that host deoxynucleoside triphosphate
      triphosphohydrolase (dNTPase) sterile alpha motif and histidine/aspartic domain
      containing protein 1 (SAMHD1), previously shown to block HIV infection in myeloid
      cells, also restricts HIV replication in resting CD4(+) T cells by hydrolyzing
      dNTPs, which are needed for reverse transcription of the virus (pages 1682-1687).

PMID- 23135509
TI  - Waking up HSCs: a new role for E-selectin.
AB  - Two anatomical niches for hematopoietic stem cells (HSCs) have been reported in
      the bone marrow, but a distinct function for each of these niches has remained
      unclear. A new role in stem cell proliferation has now been identified for the
      adhesion molecule E-selectin expressed by bone marrow endothelial cells at the
      vascular niche (pages 1651-1657).

PMID- 23135510
TI  - Protective immunity from a germinal center sanctuary.
AB  - A new study provides mechanistic insights into how live attenuated simian
      immunodeficiency virus (SIV) vaccines (LAVs) can protect monkeys from infection
      with pathogenic SIV. The authors show that replicating LAVs stimulate a
      protective immune response from a safe haven in the germinal centers of lymph
      nodes (pages 1673-1681).

PMID- 23135511
TI  - A sweet surprise for HIV broadly neutralizing antibodies.
AB  - The production of cross-reactive neutralizing antibodies is the ultimate goal in
      HIV vaccine development, but no immunogen other than HIV itself has been able to
      elicit this type of humoral immunity. In natural HIV infections, these antibodies
      take several years to develop. A new study sheds light on what may be causing
      this delay in neutralizing antibody development (pages 1688-1692).

PMID- 23135512
TI  - A sirtuin link between metabolism and heart disease.
AB  - The sirtuins (SIRTs) have gained preeminence for their roles in the response to
      caloric restriction and the regulation of aging and lifespan. A new study now
      identifies gene promoters that bind the transcription factor AP1 as targets for
      silencing by SIRT6, providing possible links between SIRT6 deficiency and
      dysregulation of insulin-like growth factor signaling, hypertrophic
      cardiomyopathy and heart failure (pages 1643-1650).

PMID- 23135513
TI  - Small airways, big challenge: measuring the unseen?
AB  - An imaging technique adapted to differentiate between chronic obstructive
      pulmonary disease phenotypes can identify small-airway pathophysiology, locate
      the disease and potentially track disease progression. This approach may be used
      as a biomarker to identify the small-airway lesion in chronic obstructive
      pulmonary disease, at an individual level in the clinic (pages 1711-1715).

PMID- 23135514
TI  - Defeating dengue: a challenge for a vaccine.

PMID- 23135515
TI  - Before epilepsy unfolds: opening up the potassium door in neonatal seizures.

PMID- 23135516
TI  - Before epilepsy unfolds: finding the epileptogenesis switch.

PMID- 23135524
TI  - Chromoanagenesis and cancer: mechanisms and consequences of localized, complex
      chromosomal rearrangements.
AB  - Next-generation sequencing of DNA from human tumors or individuals with
      developmental abnormalities has led to the discovery of a process we term
      chromoanagenesis, in which large numbers of complex rearrangements occur at one
      or a few chromosomal loci in a single catastrophic event. Two mechanisms underlie
      these rearrangements, both of which can be facilitated by a mitotic chromosome
      segregation error to produce a micronucleus containing the chromosome to undergo
      rearrangement. In the first, chromosome shattering (chromothripsis) is produced
      by mitotic entry before completion of DNA replication within the micronucleus,
      with a failure to disassemble the micronuclear envelope encapsulating the
      chromosomal fragments for random reassembly in the subsequent interphase.
      Alternatively, locally defective DNA replication initiates serial, microhomology
      mediated template switching (chromoanasynthesis) that produces local
      rearrangements with altered gene copy numbers. Complex rearrangements are present
      in a broad spectrum of tumors and in individuals with congenital or developmental
      defects, highlighting the impact of chromoanagenesis on human disease.

PMID- 23135525
TI  - Photoreceptor outer segment abnormalities and retinal sensitivity in acute zonal
      occult outer retinopathy.
AB  - PURPOSE: To investigate the relationship between retinal function and
      photoreceptor abnormalities in eyes with acute zonal occult outer retinopathy.
      METHODS: Five patients with acute zonal occult outer retinopathy underwent
      complete ophthalmologic examination, including spectral-domain optical coherence
      tomography. Spectral-domain optical coherence tomography findings were compared
      with retinal sensitivity measured by microperimetry. RESULTS: Spectral-domain
      optical coherence tomography images revealed disruptions in the inner
      segment/outer segment junction line in four of five eyes and disruptions in the
      outer segment (OS) tip lines in all eyes. Mean retinal sensitivity was 15.1 +/-
      3.6 dB in the intact OS tip regions and 6.0 +/- 6.3 dB in disrupted regions (P <
      0.001). In all eyes, disruption of the OS tip lines was also seen in regions of
      reduced retinal sensitivity, although the inner segment/outer segment was intact.
      Within the intact inner segment/outer segment regions, mean retinal sensitivity
      was 7.5 +/- 6.7 dB at locations of OS tip disruption and 15.1 +/- 3.6 dB at
      intact OS tip locations (P < 0.001). CONCLUSION: Structural abnormalities in the
      photoreceptors were correlated with visual function in eyes with acute zonal
      occult outer retinopathy. Loss of photoreceptor OS, as indicated by disruptions
      of the OS tip lines on spectral-domain optical coherence tomography, may
      represent the primary lesion in acute zonal occult outer retinopathy.

PMID- 23135526
TI  - Expression of SIRT1 in choroidal neovascular membranes.
AB  - PURPOSE: SIRT1 is a deacetylase that has been shown to be instrumental in
      embryonic and pathologic vascular formation. The purpose of this study was to
      evaluate the potential role of SIRT1 in the pathogenesis of choroidal
      neovascularization in age-related macular degeneration. METHODS: The expression
      of SIRT1 was assessed via immunohistochemistry in nine excised human choroidal
      neovascularization membranes and seven non-age-related macular degeneration donor
      eyes. Enzyme-linked immunosorbent assay-based angiogenesis arrays were used to
      assess the potential of an SIRT1 inhibitor, nicotinamide, to reduce secretion of
      10 unique proangiogenic cytokines from retinal pigment epithelial cells. RESULTS:
      SIRT1 was expressed more frequently in choroidal neovascularization membranes
      than donor eyes about vascular endothelial cells (78 vs. 29% positive cases) and
      retinal pigment epithelial cells (57 vs. 14% positive cases). SIRT1 inhibition in
      retinal pigment epithelial cells correlated with significantly decreased
      secretion of three potent proangiogenic cytokines: angiogenin, platelet-derived
      growth factor BB, and vascular endothelial growth factor A. CONCLUSION: SIRT1
      levels appear elevated in human choroidal neovascularization membranes compared
      with control eyes. Moreover, inhibition of SIRT1 activity is correlated with
      decreased secretion of potent proangiogenic cytokines. Collectively, these data
      support a potential role for SIRT1 in the pathogenesis of neovascular age-related
      macular degeneration.

PMID- 23135527
TI  - Pharmacokinetic study and effectiveness evaluation of slow-release PLGA-5
      fluorouracil microsphere.
AB  - PURPOSE: The aim was to develop a slow-release poly-lactic-co-glycolic acid
      (PLGA)-5-fluorouracil microsphere, study the pharmacokinetic characteristics as
      well as to evaluate the effectiveness and safety of this preparation on
      colorectal tumor in vivo. METHODS: The PLGA-5-fluorouracil microsphere was
      prepared based on a spray-drying method, and the drug loading of 5-fluorouracil
      (the percentage of 5-fluorouracil content in the whole microsphere), in vitro 5
      fluorouracil release profile and pharmacokinetic characteristics were carried out
      through high-performance liquid chromatography. The inhibiting effect on tumor
      growth and safety was examined using in vivo subcutaneously (s.c.) inoculated
      colorectal tumor models of nude mice. RESULTS: The size of the microsphere was
      less than 100 MUm, drug loading was 20 % and drug release time lasted as long as
      30 days. Slow-release PLGA-5-fluorouracil microsphere had longer half-life time
      (t (1/2)), larger apparent volume of distribution (V ( d )) and smaller area
      under the curve (AUC) compared with 5-fluorouracil. PLGA-5-fluorouracil
      microsphere significantly restrained tumor growth and this effect correlated with
      decreased expression of vascular endothelial growth factor in tumor cells. Body
      weight measurement and blood analysis did not suggest significant adverse effects
      on the mice during the study. CONCLUSIONS: The slow-release PLGA-5-fluorouracil
      microsphere developed here was suitable for regional use; it has pharmacokinetic
      advantages and appears safe and effective in controlling the tumor growth. This
      preparation shows promise in reducing local recurrence of colorectal cancer after
      resection, but needs further investigation.

PMID- 23135528
TI  - Hemodialysis no reason to withhold everolimus.

PMID- 23135529
TI  - Effects of estrogen and opioid blockade on blood pressure reactivity to stress in
      postmenopausal women.
AB  - Estrogen may influence coronary heart disease risk in women through the effects
      of endogenous opioids on autonomic control of blood pressure. In a randomized,
      placebo-controlled trial, we examined the combined effects of estrogen and the
      opioid antagonist, naltrexone, on blood pressure responses to psychological
      stress in 42 postmenopausal women. After 3 months of estrogen or estrogen plus
      progestin (hormone replacement therapy; n = 27) or placebo replacement,
      participants completed a mental arithmetic task after administration of .7 mg/kg
      oral naltrexone or placebo. Systolic blood pressure (SBP), diastolic blood
      pressure, mean arterial pressure and heart rate (HR) were measured at rest and
      during the arithmetic stressor. Stress produced significant increases in
      circulatory measures regardless of estrogen condition or opioid blockade (p's <
      .001). Interestingly, there was an estrogen by naltrexone interaction on SBP
      reactivity scores [F(1,38) = 4.36, p < .05], where women on estrogen with intact
      opioid receptors showed the largest SBP responses to stress, compared with all
      other conditions. This is consistent with some studies of premenopausal women,
      suggesting that estrogens may alter opioid function during stress. The
      interaction between estrogen and endogenous opioids may explain sex differences
      in opioid effects on stress reactivity in younger premenopausal women. 

PMID- 23135530
TI  - A randomized double-masked study of 0.05% cyclosporine ophthalmic emulsion in the
      treatment of meibomian gland dysfunction.
AB  - PURPOSE: To compare the efficacy of topical cyclosporine [0.05% cyclosporine A
      (CsA)] and preservative-free artificial tears in the treatment of meibomian gland
      dysfunction (MGD). METHODS: A 3-month prospective, randomized, double-masked,
      parallel-group controlled trial enrolled 70 patients with symptomatic MGD and
      unstable tear film [tear breakup time (TBUT) <8 seconds]. Patients were
      randomized to topical CsA (0.05%; group A) and 0.5% carboxymethylcellulose
      (control; group B) instilled twice daily for 3 months. Ocular Surface Disease
      Index (OSDI), lid margin inflammation, meibomian gland expression, conjunctival
      injection, corneal and interpalpebral dye staining, noninvasive tear breakup time
      (NIBUT) using the Tearscope Plus and invasive fluorescein tear breakup time
      (FBUT), and Schirmer I test were performed. RESULTS: At the 3-month evaluation,
      mean OSDI, NIBUT and FBUT, lid margin inflammation, meibomian gland
      expressibility, and tarsal injection showed significant improvement from baseline
      in group A (P<0.01, P<0.01, P<0.001, P<0.05, and P<0.001, respectively). In group
      B, only the OSDI improved significantly from baseline at 3 months (P=0.003).
      TBUTs (NIBUT and FBUT) were significantly longer in group A at all visits, and
      the mean change of TBUTs from baseline was also significantly greater in group A
      at 3 months (P<0.001). CONCLUSIONS: Topical CsA 0.05% twice daily may be helpful
      in the treatment of MGD mainly by improving tear film stability.

PMID- 23135531
TI  - Indications and outcomes of amniotic membrane transplantation in the management
      of acute stevens-johnson syndrome and toxic epidermal necrolysis:  a case-control
      study.
AB  - PURPOSE: To evaluate the indications and outcomes of amniotic membrane
      transplantation (AMT) performed within the first 2 weeks of presentation in the
      management of patients with acute Stevens-Johnson syndrome (SJS) and toxic
      epidermal necrolysis (TEN). METHODS: A retrospective chart review from January
      1998 to May 2011 identified 128 SJS/TEN patients admitted to Loyola University
      Medical Center Burn intensive care unit. The degree of initial ocular surface
      inflammation was graded as mild, moderate, or severe within the first 2 weeks of
      admission. Patients were managed either medically or with amniotic membrane (AM).
      Outcomes were graded as good [best-corrected visual acuity (BCVA)>20/40], fair
      (BCVA 20/40 to 20/200 or with ocular surface discomfort, requiring contact lens
      or reconstructive surgeries), or poor (BCVA<20/200). RESULTS: Of the 182 eyes (91
      patients) with documented inpatient eye examinations, 108 eyes (59.4%) had mild
      or no initial ocular involvement, 37 eyes (20.3%) had moderate, and 37 eyes
      (20.3%) had severe inflammation. Of the 29 patients (58 eyes) with greater than 1
      month of follow-up, 17 patients (33 eyes) were treated with medical management
      and 13 patients (25 eyes) were treated with early AM. One of the 23 eyes with
      moderate or severe presentation treated with early AMT (4.3%) resulted in a poor
      outcome within 3 months compared with 8 of 23 eyes (34.8%) that were medically
      managed (P=0.022). CONCLUSIONS: We present the first case-control study of the
      use of AM in the management of acute SJS/TEN. Early use of AMT prevents severe
      vision loss in SJS/TEN patients with initial moderate or severe ocular surface
      inflammation.

PMID- 23135532
TI  - Open clinical study of eye drops containing the fibronectin-derived peptide PHSRN
      for treatment of persistent corneal epithelial defects.
AB  - PURPOSE: We have previously shown that the fibronectin-derived peptide PHSRN (Pro
      His-Ser-Arg-Asn) promotes corneal epithelial wound healing in vivo. We have now
      examined the clinical efficacy of eye drops containing the PHSRN peptide for
      treatment of persistent epithelial defects (PEDs) of the cornea. METHODS: Seven
      patients (5 men and 2 women; mean age+/-SD, 78.3+/-9.4 years) with PEDs were
      treated by administration of eye drops containing PHSRN. The duration of the PEDs
      before treatment was 7.4+/-5.5 weeks. The eye drops were administered as 1 drop
      per eye 4 times a day. Epithelial defects were observed with a slit-lamp
      microscope and photographed during the treatment course. RESULTS: Epithelial
      defects in 5 of the 7 affected eyes (71%) responded to PHSRN treatment as
      manifested by complete epithelial resurfacing within the 4-week period after
      treatment initiation. The mean+/-SD time required for complete epithelial
      resurfacing in the 5 responding subjects was 15.8+/-3.4 days. No adverse effects
      of treatment were observed in any of the subjects. CONCLUSIONS: Eye drops
      containing the fibronectin-derived PHSRN peptide are clinically efficacious for
      the treatment of PEDs.

PMID- 23135533
TI  - Bcl-3 suppresses Tax-induced NF-kappaB activation through p65 nuclear
      translocation blockage in HTLV-1-infected cells.
AB  - Human T cell leukemia virus type 1 (HTLV-1) Tax-induced persistent activation of
      the NF-kappaB pathway is perceived as the primary cause of adult T cell leukemia
      (ATL), an aggressive leukemia caused by HTLV-1. Although elevated oncoprotein Bcl
      3 levels are found in many HTLV-1-infected T cell lines and ATL cells, the role
      of Bcl-3 in the malignant progression caused by HTLV-1 retrovirus remains poorly
      understood. We confirmed, in the present study, that the Tax-induced NF-kappaB
      activation involves the regulation of Bcl-3. Both knockdown and overexpression of
      Bcl-3 inhibit the Tax-induced NF-kappaB activation. Similarly, excessive Bcl-3
      inhibits the NF-kappaB/DNA binding activity and significantly decreases Tax
      induced p65 nuclear translocation. The present results demonstrate the
      pleiotropic roles of Bcl-3 in Tax-induced NF-kappaB activation and indicate that
      a balance in the aberrant Bcl-3 expression may be established to play an
      important role in the maintenance of proliferation and inhibition of apoptosis in
      HTLV-1-infected and ATL cells.

PMID- 23135534
TI  - Assessing modern GGA functionals for solids.
AB  - We present periodic calculations carried out with Gaussian-type basis sets on a
      test set of 21 solids with nine exchange-correlation functionals, extending
      previous works performed with two parameter-free correlation functionals (TCA and
      revTCA) which showed promising results for molecules in terms of key structural
      and energetic properties. Two LDAs and seven GGAs were considered for the
      prediction of equilibrium lattice constants, bulk moduli, and cohesive energies,
      using the same test set for all properties when possible. The effect of combining
      the TCA correlation with exchange potentials other than the PBE form originally
      used is also addressed. We find that the previously noted good accuracy of the
      parameter-free TCA functional for molecules also holds for solids, as long as a
      modified form of the exchange potential that is more biased towards solids than
      PBE is taken into account. In particular, the PBEsolTCA functional performs well
      overall for the three key structural and energetic properties considered here.

PMID- 23135535
TI  - Trinitromethyl/trinitroethyl substituted CL-20 derivatives: structurally
      interesting and remarkably high energy.
AB  - A series of trinitromethyl/trinitroethyl substituted derivatives of 2,4,6,8,10,12
      hexanitro-2,4,6,8,10,12-hexaazatetracyclo[5,5,0, 0(3.11),0(5.9)] dodecane (CL-20)
      were designed and investigated by theoretical methods. Intramolecular
      interactions between the trinitromethyl/trinitroethyl and the cage were
      investigated. The effects of trinitromethyl/trinitroethyl groups on stability of
      the parent compound are discussed. The results reveal a mutual influence of bond
      length and dihedral angle between the trinitromethyl and the cage. Compared to CL
      20, the sensitivity of derivatives is barely affected. Properties such as
      density, heat of formation and detonation performance of these novel compounds
      were also predicted. The introduction of the trinitromethyl group can
      significantly enhance the oxygen balance, density and detonation properties of
      the parent compound. The remarkable energy properties make these novel cage
      compounds competitive high energy density materials.

PMID- 23135536
TI  - Furthering the understanding of olfaction, prevalence of loss of smell and risk
      factors: a population-based survey (OLFACAT study).
AB  - OBJECTIVES: To investigate olfaction in general population, prevalence of
      olfactory dysfunction and related risk factors. DESIGN: Cross-sectional
      population-based survey, distributing four microencapsulated odorants (rose,
      banana, musk and gas) and two self-administered questionnaires (odour
      description; epidemiology/health status). SETTING: The survey was distributed to
      general population through a bilingual (Catalan, Spanish) newspaper in Catalonia
      (Spain), on December 2003. PARTICIPANTS: Newspaper readers of all ages and
      gender; 9348 surveys were analysed from the 10 783 returned. MAIN OUTCOME
      MEASURES: Characteristics of surveyed population, olfaction by age and gender,
      smell self-perception and smell impairment risk factors. Terms normosmia,
      hyposmia and anosmia were used when participants detected, recognised or
      identified all four, one to three or none of the odours, respectively. RESULTS:
      Survey profile was a 43-year-old woman with medium-high educational level, living
      in a city. Olfaction was considered normal in 80.6% (detection), 56%
      (recognition/memory) and 50.7% (identification). Prevalence of smell dysfunction
      was 19.4% for detection (0.3% anosmia, 19.1% hyposmia), 43.5% for recognition
      (0.2% anosmia, 43.3% hyposmia) and 48.8% for identification (0.8% anosmia, 48%
      hyposmia). Olfaction was worse (p<0.0001) in men than in women through all ages.
      There was a significant age-related smell detection decline however smell
      recognition and identification increased up to fourth decade and declined after
      the sixth decade of life. Risk factors for anosmia were: male gender, loss of
      smell history and poor olfactory self-perception for detection; low educational
      level, poor self-perception and pregnancy for recognition; and older age, poor
      self-perception and history of head trauma and loss of smell for identification.
      Smoking and exposure to noxious substances were mild protective factors for smell
      recognition. CONCLUSIONS: Sense of smell in women is better than in men
      suggesting a learning process during life with deterioration in older ages. Poor
      self-perception, history of smell loss, head trauma and pregnancy are potential
      risk factors for olfactory disorders.

PMID- 23135537
TI  - Wisconsin Card Sorting Test scores and clinical and sociodemographic correlates
      in Schizophrenia: multiple logistic regression analysis.
AB  - OBJECTIVES: This study investigated what clinical and sociodemographic factors
      affected Wisconsin Card Sorting Test (WCST) factor scores of patients with
      schizophrenia to evaluate parameters or items of the WCST. DESIGN: Cross
      sectional study. SETTING: Patients with schizophrenia from three hospitals
      participated. PARTICIPANTS: Participants were recruited from July 2009 to August
      2011. 131 Japanese patients with schizophrenia (84 men and 47 women, 43.5+/-13.8
      years (mean+/-SD)) entered and completed the study. Participants were recruited
      in the study if they (1) met DSM-IV criteria for schizophrenia; (2) were
      physically healthy and (3) had no mood disorders, substance abuse,
      neurodevelopmental disorders, epilepsy or mental retardation. We examined their
      basic clinical and sociodemographic factors (sex, age, education years, age of
      onset, duration of illness, chlorpromazine equivalent doses and the positive and
      negative syndrome scale (PANSS) scores). PRIMARY AND SECONDARY OUTCOME MEASURES:
      All patients carried out the WCST Keio version. Five indicators were calculated,
      including categories achieved (CA), perseverative errors in Milner (PEM) and
      Nelson (PEN), total errors (TE) and difficulties of maintaining set (DMS). From
      the principal component analysis, we identified two factors (1 and 2). We
      assessed the relationship between these factor scores and clinical and
      sociodemographic factors, using multiple logistic regression analysis. RESULTS:
      Factor 1 was mainly composed of CA, PEM, PEN and TE. Factor 2 was mainly composed
      of DMS. The factor 1 score was affected by age, education years and the PANSS
      negative scale score. The factor 2 score was affected by duration of illness.
      CONCLUSIONS: Age, education years, PANSS negative scale score and duration of
      illness affected WCST factor scores in patients with schizophrenia. Using WCST
      factor scores may reduce the possibility of type I errors due to multiple
      comparisons.

PMID- 23135538
TI  - Heat stress, health and well-being: findings from a large national cohort of Thai
      adults.
AB  - OBJECTIVES: This study aims to examine the association between self-reported heat
      stress interference with daily activities (sleeping, work, travel, housework and
      exercise) and three graded-holistic health and well-being outcomes (energy,
      emotions and life satisfaction). DESIGN: A cross-sectional study. SETTING: The
      setting is tropical and developing countries as Thailand, where high temperature
      and high humidity are common, particularly during the hottest seasons.
      PARTICIPANTS: This study is based on an ongoing national Thai Cohort Study of
      distance-learning open-university adult students (N=60 569) established in 2005
      to study the health-risk transition. PRIMARY AND SECONDARY OUTCOME MEASURES:
      Health impacts from heat stress in our study are categorised as physical health
      impacts (energy levels), mental health impacts (emotions) and well-being (life
      satisfaction). For each health and well-being outcome we report ORs and 95% CIs
      using multinomial logistic regression adjusting for a wide array of potential
      confounders. RESULTS: Negative health and well-being outcomes (low-energy level,
      emotional problems and low life satisfaction) associated with increasing
      frequency of heat stress interfering with daily activities. Adjusted ORs for
      emotional problems were between 1.5 and 4.8 and in general worse than energy
      level (between 1.31 and 2.91) and life satisfaction (between 1.10 and 2.49). The
      worst health outcomes were when heat interfered with sleeping, followed by
      interference with daily travel, work, housework and exercise. CONCLUSIONS: In
      tropical Thailand there already are substantial heat stress impacts on health and
      well-being. Increasing temperatures from climate change plus the ageing and
      urbanisation of the population could significantly worsen the situation. There is
      a need to improve public health surveillance and public awareness regarding the
      risks of heat stress in daily life.

PMID- 23135539
TI  - Seasonal change in bone, muscle and fat in professional rugby league players and
      its relationship to injury: a cohort study.
AB  - OBJECTIVES: To examine the anthropometric characteristics of an Australian
      National Rugby League team and identify the relationship to type and incidence of
      injuries sustained during a professional season. It was hypothesised that body
      composition would not change discernibly across a season and that injury would be
      negatively related to preseason bone and muscle mass. DESIGN: A repeated measure,
      prospective, observational, cohort study. SETTING: Griffith University, Gold
      Coast, Australia. PARTICIPANTS: 37 professional male Australian National Rugby
      League players, 24.3 (3.8) years of age were recruited for preseason 1 testing,
      of whom 25 were retested preseason 2. PRIMARY AND SECONDARY OUTCOME MEASURES:
      Primary outcome measures included biometrics; body composition (bone, muscle and
      fat mass; dual-energy x-ray absorptiometry; XR800, Norland Medical Systems, Inc);
      bone geometry and strength (peripheral quantitative CT; XCT 3000, Stratec);
      calcaneal broadband ultrasound attenuation (BUA; QUS-2, Quidel); diet and
      physical activity history. Secondary outcome measures included player injuries
      across a single playing season. RESULTS: Lean mass decreased progressively
      throughout the season (pre=81.45(7.76) kg; post=79.89(6.72) kg; p<=0.05), while
      whole body (WB) bone mineral density (BMD) increased until mid-season
      (pre=1.235(0.087) g/cm(2); mid=1.296(0.093) g/cm(2); p<=0.001) then decreased
      thereafter (post=1.256(0.100); p<=0.001). Start-of-season WB BMD, fat and lean
      mass, weight and tibial mass measured at the 38% site predicted bone injury
      incidence, but no other relationship was observed between body composition and
      injury. CONCLUSIONS: Significant anthropometric changes were observed in players
      across a professional rugby league season, including an overall loss of muscle
      and an initial increase, followed by a decrease in bone mass. Strong
      relationships between anthropometry and incidence of injury were not observed.
      Long-term tracking of large rugby league cohorts is indicated to obtain more
      injury data in order to examine anthropometric relationships with greater
      statistical power.

PMID- 23135540
TI  - Challenges in implementing government-directed VTE guidance for medical patients:
      a mixed methods study.
AB  - BACKGROUND: Implementing venous thromboembolism (VTE) risk assessment guidance on
      admission to hospital has proved difficult worldwide. In 2010, VTE risk
      assessment in English hospitals was linked to financial sanctions. This study
      investigated possible barriers and facilitators for VTE risk assessment in
      medical patients and evaluated the impact of local and national initiatives.
      SETTING: Acute Medical Unit in one English National Health Service university
      teaching hospital. METHODS: This was a mixed methods study; National Research
      Ethics Service approval was granted. Data were collected over four 1-week
      periods; November 2009 (1), January 2010 (2), April 2010 (3) and April 2011 (4).
      Case notes for all medical patients admitted during these periods were reviewed.
      Thirty-six staff were observed admitting 71 of these patients; 24 observed staff
      participated in a structured interview. RESULTS: 876 case notes were reviewed. In
      total, 82.1% of patients had one or more VTE risk factors and 25.3% one or more
      bleeding risks. VTE risk assessment rose from a baseline of 6.9-19.6%, following
      local initiatives, and to 98.7% following financially sanctioned government
      targets. A similar increase in appropriate prescribing of prophylaxis was seen,
      but inappropriate prescribing also rose. No staff observed in period 1 conducted
      VTE risk assessment, risk-assessment forms were largely ignored or discarded
      during period 2; and electronic recording systems available during period 3 were
      not accessed. Few patients were asked any VTE-related questions in periods 1, 2
      or 3. Interviewees' actual knowledge of VTE risk was not related to perceived
      knowledge level. Eight of the 24 staff interviewed were aware of national
      policies or guidance: none had seen them. Principal barriers identified to risk
      assessment were: involvement of multiple staff in individual admissions;
      interruptions; lack of policy awareness; time pressure and complexity of tools.
      CONCLUSIONS: National financial sanctions appear effective in implementing
      guidance, where other local measures have failed.

PMID- 23135541
TI  - Time trend in hospitalised chronic lower respiratory diseases among Danish
      building and construction workers, 1981-2009: a cohort study.
AB  - OBJECTIVES: To show trends in age-standardised hospital admission ratios (SHR)
      for chronic lower respiratory diseases, estimated for Danish construction workers
      over three time periods (1981-1990, 1991-2000, 2001-2009). DESIGN: Within
      consecutive cohorts of all male building and construction workers in Denmark,
      selected occupations: bricklayers, carpenters, electricians, painters, plumbers
      and 'other construction workers' were followed up for hospitalisation due to
      chronic lower respiratory diseases. SHR was calculated for each occupation and
      time period. Time trend was calculated for construction workers at large using
      Poisson regression. SETTING: Denmark. PARTICIPANTS: All gainfully employed male
      building and construction workers aged 20 or more. PRIMARY AND SECONDARY OUTCOME
      MEASURES: Age-standardised and gender-standardised hospitalisation ratios (SHR).
      RESULTS: The number of hospitalised construction workers at large was reduced
      from 1134 in the first 10-year period to 699 in the last 9-year period. Among all
      Danish males, it was, however, even more reduced as reflected in the expected
      number that was down from 1172 to 617. Hence, SHR increased from 97 during 1981
      1990, 100 during 1991-2000 to 113 during 2001-2009. It means that SHR increased
      with an average rate of 0.76% per year (95% CI 0.28 to 1.24) during the study
      period. A low SHR=72 (95% CI 60 to 87) was found among carpenters in 1981-1990.
      From 2001 to 2009, high SHRs were found among painters (SHR=147; 95% CI 111 to
      192) and plumbers (SHR=132; 95% CI 101 to 171). In general, the selected groups
      of construction workers had, however, a low or average SHR due to chronic lower
      respiratory diseases. CONCLUSIONS: The number of hospitalised workers, suffering
      from chronic lower respiratory diseases, was reduced over time for construction
      workers, but for all economically active men, it was reduced even more.
      Therefore, SHR due to chronic lower respiratory diseases increased over time in
      the construction industry at large.

PMID- 23135542
TI  - Weekend admissions as an independent predictor of mortality: an analysis of
      Scottish hospital admissions.
AB  - OBJECTIVES: Weekend admissions have been shown to be associated with an increased
      risk of mortality compared with weekday admissions for many diagnoses. We
      analysed emergency department admissions within the Scottish National Health
      Service to investigate whether mortality is increased in case of weekend
      emergency department admissions. DESIGN: A cohort study. SETTING: Scotland
      National Health Service (NHS) emergency departments. PARTICIPANTS: 5 271 327
      emergency department admissions between 1999 and 2009. We included all patients
      admitted via emergency departments recorded in the Scottish Morbidity Records
      (SMR01) in NHS, Scotland for whom complete demographic data were available.
      PRIMARY OUTCOME MEASURES: Death as recorded by the General Register Office (GRO).
      RESULTS: There was a significantly increased probability of death associated with
      a weekend emergency admission compared with admission on a weekday (unadjusted OR
      1.27, 95% CI 1.26 to 1.28, p<0.0001; adjusted for year of admission, gender, age,
      deprivation quintile and number of comorbidities OR 1.42, 95% CI 1.40 to 1.43,
      p<0.0001). CONCLUSIONS: Despite a general reduction in mortality over the last 11
      years, there is still a significant excess mortality associated with weekend
      emergency admissions. Further research should be undertaken to identify the
      precise mechanisms underlying this effect so that measures can be put in place to
      reduce patient mortality.

PMID- 23135543
TI  - Risk of developing tuberculosis after brief exposure in Norwegian children:
      results of a contact investigation.
AB  - OBJECTIVE: Prolonged exposure to adults with pulmonary tuberculosis is a risk
      factor for infecting children. We have studied to what extent a brief exposure
      may increase the risk of being infected in children. DESIGN: Observational study
      of a tuberculosis contact investigation. SETTING: 7 day-care centres and 4 after
      school-care centres in Norway. PARTICIPANTS: 606 1-year-old to 9-year-old
      children who were exposed briefly to a male Norwegian with smear-positive
      pulmonary tuberculosis. MAIN OUTCOME MEASURES: Number of children with latent and
      active tuberculosis detected by routine clinical examination, chest x-ray and use
      of a Mantoux tuberculin skin test (TST) and an interferon-gamma release assay
      (IGRA). RESULTS: The children were exposed to a mean of 6.9 h (range 3-18 h). 2-3
      months after the exposure, 11 children (1.8%) had a TST >=6 mm, 6 (1.0%) had TST
      4-5 mm, and 587 (97.2%) had a negative TST result. Two children (0.3%) with
      negative chest x-rays who were exposed 4.75 and 12 h, respectively, had a
      positive IGRA test result, and were diagnosed with latent tuberculosis. None
      developed active tuberculosis. CONCLUSIONS: Children from a high-income country
      attending day-care and after-school-care centres had low risk of being infected
      after brief exposure less than 18 h to an adult day-care helper with smear
      positive pulmonary tuberculosis.

PMID- 23135544
TI  - LARGE2 generates the same xylose- and glucuronic acid-containing glycan
      structures as LARGE.
AB  - LARGE (like-glycosyltransferase) and LARGE2 (glycosyltransferase-like 1B
      (GYLTL1B)) are homologous Golgi glycosyltransferases possessing two catalytic
      domains with homology to members of glycosyltransferase families GT8 and GT49.
      Mutations in human and mouse Large result in muscular dystrophy due to
      underglycosylation of dystroglycan. The systemic function of LARGE2 is unknown,
      but at a cellular level the enzyme can substitute for LARGE in glycosylating
      dystroglycan. Here, we show that LARGE2 catalyzes the same glycosylation reaction
      as LARGE. It is a bifunctional glycosyltransferase using uridine diphosphate
      (UDP)-xylose (Xyl) and UDP-glucuronic acid (GlcA) as donor sugars to produce a
      xyloglucuronan with alternating Xyl and GlcA residues.

PMID- 23135545
TI  - FeCl3-catalyzed cyclization of alpha-sulfonamido-allenes with aldehydes--the
      substituent effect.
AB  - FeCl(3)-catalyzed aza-Prins-cyclization reaction of alpha-sulfonamido-allenes
      with aldehydes afforded 1,2,3,6-tetrahydropyridine or 2,5-dihydro-1H-pyrrole
      derivatives efficiently and highly selectively. The different regioselectivity is
      probably caused by the stabilizing effect of the phenyl group on the positively
      charged allylic intermediate.

PMID- 23135546
TI  - Upconversion nanoparticles and their composite nanostructures for biomedical
      imaging and cancer therapy.
AB  - Upconversion nanoparticles (UCNPs), particularly lanthanide-doped nanocrystals,
      which emit high energy photons under excitation by the near-infrared (NIR) light,
      have found potential applications in many different fields, including
      biomedicine. Compared with traditional down-conversion fluorescence imaging, the
      NIR light excited upconversion luminescence (UCL) imaging relying on UCNPs
      exhibits improved tissue penetration depth, higher photochemical stability, and
      is free of auto-fluorescence background, which promises biomedical imaging with
      high sensitivity. On the other hand, the unique upconversion process of UCNPs may
      be utilized to activate photosensitive therapeutic agents for applications in
      cancer treatment. Moreover, the integration of UCNPs with other functional
      nanostructures could result in the obtained nanocomposites having highly enriched
      functionalities, useful in imaging-guided cancer therapies. This review article
      will focus on the biomedical imaging and cancer therapy applications of UCNPs and
      their nanocomposites, and discuss recent advances and future prospects in this
      emerging field.

PMID- 23135547
TI  - Mechanisms of hepatocellular toxicity associated with dronedarone--a comparison
      to amiodarone.
AB  - Dronedarone is a new antiarrhythmic drug with an amiodarone-like benzofuran
      structure. Shortly after its introduction, dronedarone became implicated in
      causing severe liver injury. Amiodarone is a well-known mitochondrial toxicant.
      The aim of our study was to investigate mechanisms of hepatotoxicity of
      dronedarone in vitro and to compare them with amiodarone. We used isolated rat
      liver mitochondria, primary human hepatocytes, and the human hepatoma cell line
      HepG2, which were exposed acutely or up to 24h. After exposure of primary
      hepatocytes or HepG2 cells for 24h, dronedarone and amiodarone caused
      cytotoxicity and apoptosis starting at 20 and 50 uM, respectively. The cellular
      ATP content started to decrease at 20 uM for both drugs, suggesting mitochondrial
      toxicity. Inhibition of the respiratory chain required concentrations of ~10 uM
      and was caused by an impairment of complexes I and II for both drugs. In
      parallel, mitochondrial accumulation of reactive oxygen species (ROS) was
      observed. In isolated rat liver mitochondria, acute treatment with dronedarone
      decreased the mitochondrial membrane potential, inhibited complex I, and
      uncoupled the respiratory chain. Furthermore, in acutely treated rat liver
      mitochondria and in HepG2 cells exposed for 24h, dronedarone started to inhibit
      mitochondrial beta-oxidation at 10 uM and amiodarone at 20 uM. Similar to
      amiodarone, dronedarone is an uncoupler and an inhibitor of the mitochondrial
      respiratory chain and of beta-oxidation both acutely and after exposure for 24h.
      Inhibition of mitochondrial function leads to accumulation of ROS and fatty
      acids, eventually leading to apoptosis and/or necrosis of hepatocytes.
      Mitochondrial toxicity may be an explanation for hepatotoxicity of dronedarone in
      vivo.

PMID- 23135548
TI  - Dioxin inhibits zebrafish epicardium and proepicardium development.
AB  - Embryonic exposure to the environmental contaminant and aryl hydrocarbon receptor
      agonist, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin), disrupts cardiac
      development and function in fish, birds, and mammals. In zebrafish, the temporal
      window of sensitivity to the cardiotoxic effects of TCDD coincides with
      epicardium formation. We hypothesized that this TCDD-induced heart failure
      results from disruption of epicardial development. To determine whether embryonic
      TCDD exposure inhibits epicardium and proepicardium (PE) development in
      zebrafish, we used histology and fluorescence immunocytochemistry to examine the
      epicardium formation in fish exposed to TCDD. TCDD exposure prevented epicardium
      formation. Using live imaging and in situ hybridization, we found that TCDD
      exposure blocked the formation of the PE cluster. In situ hybridization
      experiments showed that TCDD exposure also prevented the expression of the PE
      marker tcf21 at the site where the PE normally forms. TCDD also inhibited
      expansion of the epicardial layer across the developing heart: Exposure after PE
      formation was completed prevented further expansion of the epicardium. However,
      TCDD exposure did not affect epicardial cells already present. Because TCDD
      blocks epicardium formation, but is not directly toxic to the epicardium once
      complete, we propose that inhibition of epicardium formation can account for the
      window of sensitivity to TCDD cardiotoxicity in developing zebrafish. Epicardium
      development is crucial to heart development. Loss of this layer during
      development may account for most if not all of the TCDD-induced cardiotoxicity in
      zebrafish.

PMID- 23135549
TI  - The metallohormone cadmium modulates AhR-associated gene expression in the small
      intestine of rats similar to ethinyl-estradiol.
AB  - Cadmium (Cd) affects the expression of estrogen receptor (ER) and aryl
      hydrocarbon receptor (AhR)-associated genes in rat uterus and elicits estrogen
      like activity in vitro. The small intestine is highly exposed to dietary Cd which
      may mimic or antagonize estrogen action in this tissue. We investigated the
      effects of Cd and 17-alpha-ethinylestradiol (EE2) on AhR-associated gene
      expression after oral exposure of ovariectomized female Wistar rats, and
      metallothionein (Mt1a) expression as a typical metal-response marker. Mt1a in the
      small intestine was strongly induced by co-treatment with CdCl2 at 2 mg/kg b.wt
      (Cd 2) and 0.1 mg/kg b.wt EE2 than by the single compound (3-day gavage). The Cd
      2-induced down-regulation of Cyp1a1, Gsta2, and Nqo1 mRNA was not antagonized by
      pure anti-estrogen (2.5 mg/kg b.wt ZK191703 s.c., ZK). Interestingly, the EE2
      induced down-regulation of Cyp1a1, Gsta2, and Nqo1 mRNA was antagonized by Cd 2
      in vivo and in colon cancer cell lines (HT-29 and CaCo-2, treated 5 days with Cd
      1 uM and/or E2 0.01 uM) with low or no ER-beta expression. Dose dependency was
      studied after Cd exposure with drinking water (5 and 50 ppm CdCl2 equivalent to
      0.4 and 4 mg/kg b.wt; Cd 0.4, Cd 4) for 28 days and EE2 as reference. Intestinal
      Mt1a expression was dose dependently induced, while AhR target genes were down
      regulated by Cd 0.4 similar to EE2 and more pronounced than by Cd 4. We propose
      that Cd modulates intestinal AhR-associated gene expression similar to estrogens,
      but (contrary to its effects in uterus) via ER-independent and/or ER-beta
      mediated mechanisms. Our new data suggest interference of Cd with estrogen and
      AhR signaling in the small intestine.

PMID- 23135550
TI  - Polymorphisms hit the headlines.

PMID- 23135551
TI  - Guidance on asthma therapy remains murky.

PMID- 23135552
TI  - Rare-disease drugs to receive consideration on par with serious-disease drugs.

PMID- 23135553
TI  - Utah grapples with drug dispensing by physicians' specialty groups.

PMID- 23135555
TI  - Opportunities for pharmacists in the criminal justice system.

PMID- 23135556
TI  - Rocuronium and malignant hyperthermia.

PMID- 23135558
TI  - Medications in Parkinson's disease.

PMID- 23135559
TI  - Clarification about hazardous drugs.

PMID- 23135560
TI  - Implementation of a pharmacist-managed diabetes program.

PMID- 23135561
TI  - Evaluation of i.v. medication waste.

PMID- 23135562
TI  - Expanding pharmacists' role in the era of health care reform.

PMID- 23135563
TI  - Current trends in immunosuppressive therapies for renal transplant recipients.
AB  - PURPOSE: Current trends in immunosuppressive therapies for renal transplant
      recipients are reviewed. SUMMARY: The common premise for immunosuppressive
      therapies in renal transplantation is to use multiple agents to work on different
      immunologic targets. The use of a multidrug regimen allows for pharmacologic
      activity at several key steps in the T-cell replication process and lower dosages
      of each individual agent, thereby producing fewer drug-related toxicities. In
      general, there are three stages of clinical immunosuppression: induction therapy,
      maintenance therapy, and treatment of an established acute rejection episode.
      Only immunosuppressive therapies used for maintenance therapy are discussed in
      detail in this review. The most common maintenance immunosuppressive agents can
      be divided into five classes: (1) the calcineurin inhibitors (CNIs) (cyclosporine
      and tacrolimus), (2) costimulation blockers (belatacept), (3) mammalian target of
      rapamycin inhibitors (sirolimus and everolimus), (4) antiproliferatives
      (azathioprine and mycophenolic acid derivatives), and (5) corticosteroids.
      Immunosuppressive regimens vary among transplantation centers but most often
      include a CNI and an adjuvant agent, with or without corticosteroids. Selection
      of appropriate immunosuppressive regimens should be patient specific, taking into
      account the medications' pharmacologic properties, adverse-event profile, and
      potential drug-drug interactions, as well as the patient's preexisting diseases,
      risk of rejection, and medication regimen. CONCLUSION: Advancements in transplant
      immunosuppression have resulted in a significant reduction in acute cellular
      rejection and a modest increase in long-term patient and graft survival. Because
      the optimal immunosuppression regimen is still unknown, immunosuppressant use
      should be influenced by institutional preference and tailored to the immunologic
      risk of the patient and adverse-effect profile of the drug.

PMID- 23135564
TI  - Pharmacist interdependent prescribing: a new model for optimizing patient
      outcomes.

PMID- 23135565
TI  - Survey of Alberta hospital pharmacists' perspectives on additional prescribing
      authorization.
AB  - PURPOSE: The results of a survey to determine reasons for the slow adoption of
      prescribing authority by hospital pharmacists in the Canadian province of Alberta
      are presented. METHODS: A Web-based survey was conducted to elucidate pharmacist
      perspectives on additional prescribing authorization (APA), which permits
      independent prescribing by Alberta pharmacists who complete a peer-reviewed
      application process (at the time of the survey, only 52 hospital pharmacists had
      been granted APA). The survey elicited demographic data and practice
      characteristics and explored perspectives on APA and their influence on the
      decision to apply or not apply for APA. RESULTS: Approximately 500 pharmacists
      were invited to participate in the survey, and 314 (63%) responded and met the
      study inclusion criteria. The perceived relevancy and value of APA to
      respondents' practice activities and potential benefits such as increased
      efficiency appear to be important factors motivating pharmacists to apply for
      APA. A perception that the application process is too lengthy and concerns about
      potential drawbacks (e.g., increased liability risk, inability to fulfill patient
      follow-up and documentation requirements) appear to be strong influences on
      decisions to forgo pursuing APA. CONCLUSION: Results of a survey of hospital
      pharmacists in Alberta suggest that APA is adopted more often by pharmacists
      whose primary focus is ambulatory care, those with higher levels of education,
      and those with more colleagues who also have APA. The perceived relevancy and
      value of APA to practice activities and the potential for increased efficiency
      and job satisfaction appear to be strong influences on decisions to seek APA.

PMID- 23135566
TI  - Safety and effectiveness outcomes of an inpatient collaborative drug therapy
      management service for direct thrombin inhibitors.
AB  - PURPOSE: The impact of a collaborative drug therapy management (CDTM) agreement
      enabling pharmacist-managed direct thrombin inhibitor (DTI) therapy was
      evaluated. METHODS: A retrospective chart review was conducted to compare
      selected outcome measures between cohorts of adults who received argatroban or
      bivalirudin therapy for suspected heparin-induced thrombocytopenia (HIT) before
      (n = 25) and after (n = 25) the implementation of an institutional DTI protocol
      under which properly trained and credentialed pharmacists have a primary role in
      dosing and monitoring DTI infusions. The primary endpoints were the mean time to
      attainment of activated partial thromboplastin time (aPTT) values in a specified
      therapeutic range and the proportion of total inpatient treatment time during
      which aPTT values were in that range. Secondary endpoints included the incidence
      of major and minor bleeding and the incidence of medication errors. RESULTS:
      After implementation of the DTI protocol, therapeutic aPTT values were achieved
      more rapidly (a mean of 3.4 hours in the postimplementation cohort versus a mean
      of 7.7 hours in the preimplementation cohort, p = 0.009) and maintained more
      consistently. Rates of bleeding and overall mortality were similar in the two
      groups; the frequencies of documented medication errors were 12% and 40% in the
      postimplementation and preimplementation cohorts, respectively (p = 0.05).
      CONCLUSION: A pharmacist-driven DTI program resulted in improved effectiveness
      and safety outcomes, as demonstrated by improved attainment of target aPTT values
      and a decreased frequency of medication errors.

PMID- 23135567
TI  - Extended stability of intravenous acetaminophen in syringes and opened vials.
AB  - PURPOSE: The stability of i.v. acetaminophen beyond the manufacturer-recommended
      usage limit of six hours for opened vials was evaluated. METHODS: Intravenous
      acetaminophen (10 mg/mL) was obtained. Three identical samples of 100 mg (10 mL
      in a 10-mL syringe), 250 mg (25 mL in a 30-mL syringe), 500 mg (50 mL in a 60-mL
      syringe), 250 mg (25 mL in the original vial), and 900 mg (90 mL in original
      vial) were prepared. A 0.5-mL volume of each sample was withdrawn, diluted with
      mobile phase to an expected concentration of 50 MUg/mL, and assayed in duplicate
      using high-performance liquid chromatography immediately after preparation and at
      24, 48, 72, and 84 hours. The samples were visually inspected for any change in
      color, and pH was assessed at each time of analysis. The stability of the
      solutions was determined by calculating the percentage of the initial
      acetaminophen concentration remaining at each test hour. Stability was defined as
      the retention of at least 90% of the initial acetaminophen concentration.
      RESULTS: At least 99% of the initial concentration of acetaminophen remained in
      the original vials and polypropylene syringes throughout the 84-hour study
      period. There were no detectable changes in color, pH, visible microbial growth,
      or visible drug precipitation. CONCLUSION: Intravenous acetaminophen (10 mg/mL)
      was physically and chemically stable in a range of volumes for up to 84 hours in
      the opened vials and in polypropylene syringes at room temperature.

PMID- 23135568
TI  - Injectable administration privileges among pharmacists in the United States.
AB  - PURPOSE: Privileges for administering nonvaccine injectable medications among
      pharmacists in the United States were assessed. METHODS: An e-mail inquiry on
      specific protocols for the administration of injectables was sent to the state
      boards of pharmacy (BOPs) for all 50 states and the District of Columbia that had
      a valid e-mail address listed on the National Association of Boards of Pharmacy
      website. Respondents were encouraged to include in their response a link to state
      regulations so that information from the BOP laws on privileges for administering
      injectables could be closely reviewed. State guidelines were reviewed online for
      all BOPs that did not respond to the first e-mail in order to complete the study.
      A follow-up e-mail was sent only to those respondents whose states granted
      pharmacists privileges for administering nonvaccine injectables in order to
      clarify the specific drugs allowed to be injected by pharmacists. RESULTS:
      Responses received included either links to state regulations or explicit
      statements of the rules regarding pharmacists' injectable privileges. A total of
      21 states currently grant pharmacists articulate written information or rules
      pertaining to the privilege of administering nonvaccine injectable products.
      Authority is provided through collaborative practice agreements for most states.
      Products administered by pharmacists vary by state. CONCLUSION: Pharmacists in 21
      states were found to have privileges for administering injectable medications
      other than vaccines. Pharmacists were authorized to administer these drugs
      through completion of training approved by the Accreditation Council for Pharmacy
      Education, collaborative practice agreements, valid prescription orders, board
      certification, or other broad privileges as specified in state regulations.

PMID- 23135569
TI  - California court's decision regarding a physician's petition for reinstatement of
      his medical license.

PMID- 23135570
TI  - Hyperthermia inhibits the proliferation and invasive ability of mouse malignant
      melanoma through TGF-beta(1).
AB  - The degradation of basement membranes by tumor cells involves secretion and
      activation of proteinases, such as the matrix metalloproteinases (MMPs), and
      results from an imbalance between their inhibitors and activators that are
      controlled by various growth factors or cytokines, among which TGF-beta(1) may be
      the most intriguing. In order to study the therapeutic effect and molecular
      mechanism of hyperthermia on aggressive malignant melanoma, the expression levels
      of TGF-beta(1) and Smad4 in B16F10 cells were dynamically analyzed by RT-PCR and
      western blotting for 24 h after heat treatment, from which time-dependent changes
      were determined. As expected, the proliferation and invasive ability of B16F10
      cells were suppressed strongly by heat treatment. Furthermore, we compared the
      expression of TGF-beta(1) in melanoma mouse models before and after magnetic
      fluid hyperthermia (MFH) in vivo. After hyperthermia, the tumor growth rate was
      reduced with a decline in TGF-beta(1) protein expression. We conclude that
      changes in the TGF-beta(1) pathway induced by hyperthermia may be an important
      part of the molecular mechanism involved.

PMID- 23135572
TI  - Validity of the proliferation markers Ki67, TOP2A, and RacGAP1 in molecular
      subgroups of breast cancer.
AB  - High proliferation rates are characteristic of cancer, and proliferation markers
      make up the majority of genes included in RNA-based prognostic gene signatures
      applied for breast cancer patients. Based on prior data on differences in
      molecular subgroups of breast cancer, we hypothesized that the significance of
      single proliferation markers might differ in luminal, Her2-positive and triple
      negative subtypes. Therefore, we compared mRNA expression data of Ki67, TOP2A,
      and RacGAP1 using a pool of 562 Affymetrix U133A microarrays from breast cancer
      samples. "Luminal," "triple-negative," and "Her2-positive" subcohorts were
      defined by ESR1 and ERBB2 mRNA expression using pre-defined cut-offs. The
      analysis of the three potential proliferation markers revealed subtype-specific
      differences: in luminal carcinomas, expression of all three markers was a
      significant indictor of early recurrence in univariate and multivariate analysis,
      but RacGAP1 was superior to Ki67 and TOP2A in significance. In triple-negative
      tumors, only Ki67 was a significant and independent marker, whereas none of the
      markers showed a significant prognostic impact in Her2-positive cases. Within the
      group of luminal carcinomas, the proliferation markers had different impact
      depending on the treatment of patients: in untreated patients, Ki67, TOP2A, and
      RacGAP1 were significant and independent prognostic markers. In chemotherapy
      treated patients, overexpression of all three markers was predictive for early
      recurrence, but only RacGAP1 retained significance in multivariate analysis. In
      contrast, RacGAP1 was the only predictive proliferation marker in the endocrine
      treatment group. These data point to subtype-specific differences in the
      relevance of proliferation-associated genes, and RacGAP1 might be a strong
      prognostic and predictive marker in the luminal subgroup.

PMID- 23135575
TI  - The ideal design of the ileoanal pouch:  one for each patient?

PMID- 23135573
TI  - Hypothesized role of pregnancy hormones on HER2+ breast tumor development.
AB  - Breast cancer incidence rates have declined among older but not younger women;
      the latter are more likely to be diagnosed with breast cancers carrying a poor
      prognosis. Epidemiological evidence supports an increase in breast cancer
      incidence following pregnancy with risk elevated as much as 10 years post-partum.
      We investigated the association between years since last full-term pregnancy at
      the time of diagnosis (<=10 or >10 years) and breast tumor subtype in a case
      series of premenopausal Hispanic women (n = 627). Participants were recruited in
      the United States, Mexico, and Spain. Cases with known estrogen receptor (ER),
      progesterone receptor (PR), and HER2 status, with one or more full-term
      pregnancies >=1 year prior to diagnosis were eligible for this analysis. Cases
      were classified into three tumor subtypes according to hormone receptor (HR+ =
      ER+ and/or PR+; HR- = ER- and PR-) expression and HER2 status: HR+/HER2-, HER2+
      (regardless of HR), and triple negative breast cancer. Case-only odds ratios
      (ORs) and 95 % confidence intervals (CIs) were calculated for HER2+ tumors in
      reference to HR+/HER2- tumors. Participants were pooled in a mixed-effects
      logistic regression model with years since pregnancy as a fixed effect and study
      site as a random effect. When compared to HR+/HER2- cases, women with HER2+
      tumors were more likely be diagnosed in the post-partum period of <=10 years (OR
      = 1.68; 95 % CI, 1.12-2.52). The effect was present across all source populations
      and independent of the HR status of the HER2+ tumor. Adjusting for age at
      diagnosis (<=45 or >45 years) did not materially alter our results (OR = 1.78; 95
      % CI, 1.08-2.93). These findings support the novel hypothesis that factors
      associated with the post-partum breast, possibly hormonal, are involved in the
      development of HER2+ tumors.

PMID- 23135576
TI  - Tumor scatter and the invisible margin.

PMID- 23135577
TI  - Tumor scatter after neoadjuvant therapy for rectal cancer:  are we dealing with
      an invisible margin?
AB  - BACKGROUND: After the impressive response of rectal cancers to neoadjuvant
      therapy, it seems reasonable to ask: can we can excise the small ulcer locally or
      avoid a radical resection if there is no gross residual tumor? Does gross
      response reflect what happens to tumor cells microscopically after radiation?
      OBJECTIVE: The aim of this study was to identify microscopic tumor cell response
      to radiation. DESIGN: This study is a retrospective review of a prospectively
      collected database. SETTING: This investigation was conducted at a single
      tertiary medical center. PATIENTS: Patients were selected who had elective
      radical resection for rectal cancer after preoperative chemotherapy and radiation
      performed by 2 colorectal surgeons between 2006 and 2011. MAIN OUTCOME MEASURES:
      The primary outcome measured was tumor presence after radiation therapy RESULTS:
      Of the 75 patients, 20 patients were complete responders and 55 had residual
      cancer. Of these patients, 28 had no tumor cells seen outside the gross ulcer,
      and 27 (49.1%) had tumor outside the visible ulcer or microscopic tumor present
      with no overlying ulcer. Of these tumors, 81.5% were skewed away from the ulcer
      center. The mean distance of distal scatter was 1.0 cm from the visible ulcer
      edge to a maximum of 3 cm; 3 patients had tumor cells more than 2 cm distal to
      the visible ulcer edge. Tumor scatter outside the ulcer was not associated with
      poor prognostic factors, such as nodal and distant disease, perineural invasion,
      or mucin; however, it was associated with lymphovascular invasion (chi2 = 4.12, p
      = 0.038) LIMITATIONS: There was limited access to clinical information gathered
      outside our institution. CONCLUSIONS: Our study suggests that 1) after radiation,
      the gross ulcer cannot be used to determine the sole area of potential residual
      tumor, 2) cancer cells may be found up to 3 cm distally from the gross ulcer, so
      the traditional 2-cm margin may not be adequate, and 3) local excision of the
      ulcer or no excision after apparent complete response appears to be insufficient
      treatment for rectal cancer.

PMID- 23135578
TI  - Multimodality salvage of recurrent disease after local excision for rectal
      cancer.
AB  - BACKGROUND: Local excision, alone or in combination with chemoradiation, is
      increasingly considered for rectal cancer. Higher risks of disease recurrence
      have been demonstrated after local excision. OBJECTIVE: The aim of this study was
      to examine the outcomes of current-era multimodality salvage for recurrent rectal
      cancer after local excision. DESIGN: This was a single-institutional
      retrospective study. SETTINGS: This study was conducted at a tertiary-referral
      cancer center between 1993 and 2011. PATIENTS: Forty-six patients with recurrent
      rectal cancer after initial local excision were included. INTERVENTION:
      Multimodality salvage treatment was performed as appropriate. MAIN OUTCOME
      MEASURES: The primary outcomes measured were the pattern of disease recurrence,
      salvage treatments, and resultant overall and re-recurrence-free survival.
      RESULTS: After the initial local excision, recurrent disease was diagnosed after
      a median interval of 1.9 years: local/regionally in 67%, distantly in 18%, and
      both in 15%. Four patients (9%) had recurrence that was unsalvageable, 2 (4%)
      declined treatment, and 40 (87%) underwent surgical salvage. Preoperative
      chemoradiation was given in 30 (75%) patients. The R0 resection rate was 80%,
      requiring multivisceral resection (33%), total pelvic exenteration (5%), and
      metastasectomy (25%). The rate of sphincter preservation was 33%, and
      perioperative morbidity was 50%. The first site of failure after salvage was
      distant in 38% and was local only in 10%. The 5-year overall and 3-year re
      recurrence-free survival were 63% and 43%. Pathologic stage at initial local
      excision, receipt of neoadjuvant chemoradiation before local excision, recurrence
      pattern after local excision, pathologic stage at salvage, and R0 resection at
      salvage influenced re-recurrence-free survival. LIMITATIONS: This study was
      limited by the referral and selection biases inherent in a small study cohort.
      CONCLUSIONS: Failure after local excision for rectal cancer may not be
      salvageable. When feasible, multimodality treatment, including multivisceral
      resection, pelvic irradiation, and chemotherapy, was associated with potentially
      lasting treatment-related morbidities and only modest success in long-term
      disease control. These findings should be compared with the expected stage
      specific outcomes of standard proctectomy for early-stage rectal cancer, when
      local excision is being considered.

PMID- 23135579
TI  - Depth of mesorectal extension has prognostic significance in patients with T3
      rectal cancer.
AB  - BACKGROUND: More than half of all rectal cancers are T3 lesions, but they are
      classified as a single-stage category. OBJECTIVE: The aim of this study was to
      validate prognostic significance of mesorectal extension depth in T3 rectal
      cancer. DESIGN: This study is a retrospective analysis of oncologic outcomes of
      patients with T3 rectal cancer grouped by mesorectal extension depth (T3a, <1 mm;
      T3b, 1-5 mm; T3c, 5-15 mm; T3d, >15 mm). SETTINGS: This study was conducted at a
      tertiary referral cancer hospital. PATIENTS: From 2003 to 2009, 291 patients who
      underwent a curative surgery were included. MAIN OUTCOME MEASURES: Oncologic
      outcomes in terms of disease-free survival were analyzed. RESULTS: The 5-year
      disease-free survival rate according to T3 subclassification was 86.5% for T3a,
      74.2% for T3b, 58.3% for T3c, and 29.0% for T3d. It was significantly higher in
      T3a,b tumors than that in T3c,d tumors (77.6% vs 55.2%, p < 0.001). On univariate
      and multivariate analysis, prognostic factors affecting recurrence were
      preoperative CEA level >= 5 ng/mL (HR 2.617, 95% CI 1.620-4.226), lymph node
      metastasis (HR 3.347, 95% CI 1.834-6.566), and mesorectal extension depth >5 mm
      (HR 1.661, 95% CI 1.013-2.725). In subgroup analysis, independent prognostic
      factors were preoperative CEA level and mesorectal extension depth >5 mm for 200
      patients with ypT3 rectal cancer and preoperative CEA level and lymph node
      metastasis for 91 patients with pT3 rectal cancer. LIMITATIONS: This study lacks
      quality of surgery plane evaluation because of its retrospective nature.
      Moreover, pathologic examination was not done with a whole-mount section.
      CONCLUSIONS: Depth of mesorectal extension >5 mm is a significant prognostic
      factor in patients with T3 rectal cancer. Depth of mesorectal extension
      especially may be more important than the nodal status in predicting the
      oncologic outcome for patients who had received preoperative chemoradiotherapy.

PMID- 23135580
TI  - Outcomes after rectal cancer surgery in elderly nursing home residents.
AB  - BACKGROUND: As the population ages, an increasing number of elderly persons will
      undergo surgery for rectal cancer. The use of sphincter-sparing surgery in frail
      older adults is controversial. OBJECTIVE: The aim of this study was to examine
      mortality and bowel function after proctectomy in nursing home residents. DESIGN:
      This is a retrospective cohort study. SETTING: This investigation was conducted
      in nursing homes in the United States contracted with the Center for Medicare and
      Medicaid Services. PATIENTS: Nursing home residents age 65 and older undergoing
      proctectomy for rectal cancer (2000-2005) were included. MAIN OUTCOME MEASURES:
      The primary outcomes measured were fecal incontinence and the 1-year mortality
      rate. RESULTS: Operative mortality was 18% after proctectomy with permanent
      colostomy and 13% after sphincter-sparing proctectomy (adjusted relative risk,
      1.25 (95% CI 0.90-1.73), p = 0.188). One-year mortality was high: 40% after
      sphincter-sparing proctectomy and 51% after proctectomy with permanent colostomy
      (adjusted hazard ratio 1.32 (95% CI 1.09-1.60), p = 0.004). After sphincter
      sparing proctectomy, 37% of residents were incontinent of feces. Residents with
      the poorest functional status (Minimum Data Set-Activities of Daily Living
      quartile 4) were significantly more likely to be incontinent of feces than
      residents with the best functional status (Minimum Data Set-Activities of Daily
      Living quartile 1) (76% vs 13%, adjusted relative risk 3.28 (95% CI 1.74- 6.18),
      p= 0.0002). Fecal incontinence was also associated with dementia (adjusted
      relative risk 1.55 (95% CI 1.15-2.09), p = 0.004) and renal failure (adjusted
      relative risk 1.93 (95% CI 1.10-3.38), p = 0.022). LIMITATIONS: Measures of fecal
      incontinence in nursing home registries are not as well studied as those commonly
      used in clinical practice. CONCLUSIONS: Sphincter-sparing proctectomy in nursing
      home residents is frequently associated with postoperative fecal incontinence and
      should be considered only for continent patients with good functional status.

PMID- 23135581
TI  - Treatment of high-grade anal intraepithelial neoplasia with infrared coagulation
      in a primary care population of HIV-infected men and women.
AB  - BACKGROUND: High-grade anal intraepithelial neoplasia, the putative anal
      carcinoma precursor, is more common in HIV-infected persons. The ideal treatment
      for these lesions has not been established. OBJECTIVE: The aim of this study was
      to evaluate the effectiveness of infrared coagulation treatment for high-grade
      anal intraepithelial neoplasia. DESIGN: This is a prospective cohort study.
      Patients with high-grade anal intraepithelial neoplasia either received infrared
      coagulation treatment or voluntarily did not receive treatment and were
      reevaluated at a subsequent time point. SETTING: This investigation was performed
      at a Ryan White-funded clinic located in the United States. PATIENTS: HIV
      infected men and women with biopsy-confirmed high-grade anal intraepithelial
      neoplasia were included. MAIN OUTCOME MEASURES: The primary outcome measured was
      the histology collected by high-resolution anoscopy-directed biopsy. RESULTS: The
      study included 124 patients. Of 42 patients who either delayed treatment or were
      not treated, 37 (88%; 95% CI = 74%-96%) still had high-grade anal intraepithelial
      neoplasia on reevaluation and 2 (5%; 95%CI = 1%-16%) had squamous-cell carcinoma.
      Of 98 patients who received infrared coagulation treatment, 73 (74%; 95% CI = 65%
      83%) patients had no evidence of high-grade anal intraepithelial neoplasia on
      their first posttreatment evaluation, and none had progressed to squamous-cell
      carcinoma (p < 0.0001 in comparison with untreated). Upon completing all initial
      and, if necessary, follow-up treatment, 85 (87%; 95% CI = 78%-93%) patients
      treated by infrared coagulation had no evidence of high-grade anal
      intraepithelial neoplasia and none had progressed to squamous-cell carcinoma.
      LIMITATIONS: The study population may not be representative of the general
      population, the study environment was uncontrolled, and patients were not
      randomly assigned to treatment. CONCLUSIONS: Infrared coagulation is an effective
      treatment for high-grade anal intraepithelial neoplasia.

PMID- 23135582
TI  - Anal cancer screening in HIV-infected patients: is it time to screen them all?
AB  - BACKGROUND: Annual screening for anal cancer is recommended only for HIV patients
      at increased risk: men who have sex with men, individuals with a history of
      anogenital warts, and women with cervical dysplasia. OBJECTIVE: The aim of this
      study was to examine the screening outcomes between HIV populations with and
      without these risk factors. METHODS: We reviewed the records of all HIV patients
      referred for anal cytology and high-resolution anoscopy from June 2009 to June
      2010. Patients were stratified into an increased-risk group or a standard-risk
      group. MAIN OUTCOME: Of the 329 evaluable patients, 285 (89.8% men, 10.2% women,
      mean age 46 +/- 10 years) were classified to the increased-risk group, whereas 44
      (72.7% men, 27.3% women, mean age 52 +/- 8 years) were included in the standard
      risk group. Male sex, white race, sexual orientation, past and current receptive
      anal intercourse, noncompliance with condom use, and absence of a new sexual
      partner were significantly different in the increased-risk group in comparison
      with the standard-risk group. In the increased-risk group, 187 (66.5%) patients
      had biopsy-proven dysplasia of which 118 (42.0%) had high-grade disease. In the
      standard-risk group, 15 (34.9%) patients had biopsy-proven dysplasia of which 7
      (16.3%) had high-grade disease. Cytology detected biopsy-confirmed high-grade
      dysplasia only in 23 of 118 (19.5%) patients in the increased-risk group and in 2
      of 7 (28.6%) patients in the standard-risk group. Kappa agreement in detecting
      high-grade disease was low for both increased-risk and standard-risk groups: 0.16
      (95% CI 0.07-0.23) and 0.40 (95% CI 0.02-0.40). LIMITATIONS: Our study is a chart
      based retrospective review of data with a small female population. Histology
      reports came from 2 different laboratories. CONCLUSION: High-grade anal dysplasia
      was prevalent even among HIV patients who only have standard risk factors. Anal
      cytology and high-resolution anoscopy have poor agreement. We suggest considering
      annual screening by using high-resolution anoscopy in addition to cytology for
      all HIV patients regardless of risk factors.

PMID- 23135583
TI  - The ideal ileal-pouch design: a long-term randomized control trial of J- vs W
      pouch construction.
AB  - BACKGROUND: The IPAA has become established as the preferred technique for
      restoring intestinal continuity postproctocolectomy. The ideal pouch design has
      not been established. W-pouches may give better functional results owing to
      increased volume, whereas the J-pouch's advantage is its straightforward
      construction. We report short- and long-term results of an randomized control
      trial designed to establish the ideal pouch. DESIGN: Ninety-four patients were
      randomly assigned to J- and W-pouches (49:45) and assessed at 1 and 8.7 years
      postoperatively. Assessment was questionnaire based and designed to assess pouch
      function and patient quality of life. RESULTS: Eighty-five percent of patients
      were followed up at 1 year, and 68% were followed up at 8.7 years. At 1 year,
      there was a significant difference in 24-hour bowel movement frequency J- vs W
      pouches 7 vs 5(p < 0.001) and in daytime frequency J- vs W-pouches 6 vs 4 (p <
      0.001), with no difference in nocturnal function. At 9-year follow-up, function
      had equilibrated between the 2 groups: 24-hour bowel movement frequency J- vs W
      pouches 6.5 vs 6 (p = 0.36), daytime frequency 5.5 vs 5 (p = 0.233), and
      nocturnal function 1 vs 1 (p = 0.987). Mean operating time of J- and W-pouches
      was 195 and 215 minutes (p < 0.05). All other parameters, pad usage, urgency,
      incontinence, and quality of life, did not differ significantly between groups.
      CONCLUSION: These data demonstrate that the theoretical functional advantage
      conferred on the W-pouch by its greater volume exists only in the short term and
      is of little consequence to patients' long-term quality of life. This advantage
      is attenuated as the pouches mature, resulting in no disparity in pouch function.
      This, combined with the more consistent, efficient, and easily taught
      construction of the J-pouch, should conclusively establish it as the optimum
      ileal-pouch design.

PMID- 23135584
TI  - Drivers of cost after surgical and medical therapy for chronic ulcerative
      colitis: a nested case-cohort study in Olmsted County, Minnesota.
AB  - BACKGROUND: We previously reported the costs associated with surgery for chronic
      ulcerative colitis in the Olmsted County population and found that direct medical
      costs after surgery were significantly reduced compared with before surgery.
      However, in that study, costs associated with chronic medical therapy for
      ulcerative colitis were not assessed in nonsurgical patients. OBJECTIVE: To gain
      insight into the drivers of costs of treatment for chronic ulcerative colitis, we
      assessed direct costs after surgical and medical therapy in 120 patients in the
      Rochester Epidemiology Project database. METHODS: A cohort of 60 patients who
      recovered from surgery for ulcerative colitis from 1988 to 2006 were 1:1 matched
      by age, sex, and referent year to medically managed patients. Direct health care
      costs were estimated from an institutional database, and observed cost
      differences over a 2-year period were calculated. Statistical significance was
      assessed by paired t tests and bootstrapping; mean costs are adjusted 2009
      constant dollars. RESULTS: Two-year direct health care costs in the surgical and
      medical cohorts were $10,328 vs $6,586 (p = 0.19). In the surgical cohort, Brooke
      ileostomy patients were observed to have higher costs than patients with ileal
      pouches ([INCREMENT]$8187, p = 0.04), and after ileal pouch, pouchitis was
      associated with increased costs ([INCREMENT]$12,763, p < 0.01). In the medical
      cohort, disease extent ([INCREMENT]$6059, p = 0.04) but not disease severity was
      associated with increased costs. LIMITATIONS: This study was limited by the
      relatively small population size and by its performance in a county with a
      tertiary referral center. CONCLUSIONS: Before the introduction of biologic
      therapies for ulcerative colitis, patients were observed to have similar health
      care costs after surgical and medical therapy. In medically treated patients,
      disease extent was associated with increased costs, whereas in surgically treated
      patients, permanent ileostomy and pouchitis were observed to be associated with
      increased costs.

PMID- 23135585
TI  - Ileostomy pathway virtually eliminates readmissions for dehydration in new
      ostomates.
AB  - BACKGROUND: New ileostomates face significant physical and psychological
      adaptations. Despite advanced resources, such as wound, ostomy, and continence
      nurses, we observed a high readmission rate for dehydration among patients with
      new ileostomies. OBJECTIVE: Our goal was to create a pathway to reduce
      readmission and facilitate patient education and well-being. DESIGN: The
      'Ileostomy Pathway' was established by a collaborative group at Beth Israel
      Deaconess Medical Center. A standardized set of patient education tools was
      developed to be used throughout the perioperative process. Patient's education
      started with the preoperative visit. All patients were directly engaged in ostomy
      management and trained in a stepwise progression. Patients were discharged from
      the hospital with flow sheets, supplies for recording intake/output, and visiting
      nurse services. Prospectively collected data from the first 7 months was compared
      with a retrospective database of the previous 4 years. SETTINGS: This study was
      conducted at a tertiary academic center. PATIENTS: Patients with a new permanent
      or temporary ileostomy were included. INTERVENTIONS: A new ileostomy pathway was
      created. MAIN OUTCOME MEASURES: The primary outcome measured was readmission
      rates. RESULTS: One hundred sixty-one patients were assigned to prepathway
      implementation and 42 were assigned to postpathway implementation. One hundred
      three of 203 (50.7%) patients were men, and 58 of 203 (28.6%) patients had
      permanent ostomies. Overall readmission rate was 35.4% and 21.4% for the
      prepathway and postpathway groups. The readmission rate for dehydration was 15.5%
      (25/161) for prepathway patients, but dropped to 0% in the study group. The
      average length of stay after creation of the new ostomy was 7.5 days and 6.6 days
      for prepathway and postpathway groups. LIMITATIONS: This study was limited by its
      small sample size and the lack of randomization. CONCLUSIONS: A simple,
      educational program for new ileostomy patients that includes preoperative
      teaching, standardized teaching materials, in-hospital engagement, observed
      management, and postdischarge tracking of intake and output is very effective in
      decreasing hospital readmission. The average length of stay remained stable,
      despite the addition of this teaching program to our perioperative/inpatient
      care.

PMID- 23135586
TI  - To LIFT or to flap? Which surgery to perform following seton insertion for high
      anal fistula?
AB  - BACKGROUND: The ideal surgery following seton insertion for high anal fistulas
      remains debatable. OBJECTIVE: This study aimed to compare the success between the
      endorectal advancement flap and the ligation of intersphincteric fistula tract
      techniques as the definitive procedure following seton placement. DESIGN: This
      study is a retrospective review. SETTINGS: This study was conducted at the
      Division of Colorectal Surgery, University Surgical Cluster, National University
      Health System, Singapore, between April 2006 and July 2011. PATIENTS AND
      INTERVENTIONS: After seton placement for high anal fistulas, 31 and 24 patients
      underwent the endorectal advancement flap and the ligation of intersphincteric
      fistula tract procedures. MAIN OUTCOME MEASURES: Failure was defined as the
      nonhealing of the surgical wounds or persistent discharge at the external
      opening. RESULTS: We identified 31 patients with a median age of 49 (range, 19
      74) years in the endorectal advancement flap group. The median interval from the
      seton procedure to the flap procedure was 13 (range, 4-284) weeks. Over a median
      follow up of 6 (range, 2-26) months, 29 (93.5%) patients had successful outcomes.
      There were 24 patients, median age 41 (range, 16-75) years, in the ligation of
      intersphincteric fistula tract group. The median interval from the seton
      placement to the definitive surgery was 14 (range, 8-74) weeks. Over a median
      follow-up of 13 (range, 4-67) months, 15 (62.5%) patients had successful
      outcomes. Hence when performed as the initial definitive procedure after a seton,
      the endorectal advancement flap technique had a significantly higher success rate
      in comparison with the ligation of intersphincteric fistula tract approach (93.5%
      vs 62.5%) (p = 0.006). CONCLUSION: In patients who have had seton placement for
      high anal fistulas, the endorectal advancement flap technique is associated with
      better short-term outcomes in comparison with the ligation of intersphincteric
      fistula tract technique.

PMID- 23135587
TI  - Neuromodulation for fecal and urinary incontinence:  functional results in 57
      consecutive patients from a single institution.
AB  - BACKGROUND: Sacral nerve stimulation is a recognized treatment for fecal and
      urinary incontinence. Few articles have been published about patients presenting
      with both types of incontinence. OBJECTIVE: The aim of this study was to report
      the functional results in patients operated on for simultaneous fecal and urinary
      incontinence by the use of sacral nerve stimulation. DESIGN: This study is a
      retrospective analysis of prospectively collected data. SETTINGS: The
      investigation was conducted in the academic departments of colorectal surgery and
      urology. PATIENTS: Between January 2001 and March 2010, 57 consecutive patients
      (54 women) with a mean age of 58 years (range, 16-76) were included.
      INTERVENTIONS: Two-stage sacral nerve modulation (test and implant) was
      performed. MAIN OUTCOME MEASURES: Functional study before testing, at 6 months,
      and at the end of follow-up after implantation included the use of the Cleveland
      Clinic incontinence score, Urinary Symptoms Profile, Fecal Incontinence Quality
      of Life score, and the Ditrovie score. Patient satisfaction with the technique
      was evaluated at a median follow-up of 62.8 months. RESULTS: : Fecal incontinence
      improved from 14.1/20 to 7.2/20 at 6 months and 6.9/20 at the end of follow-up.
      Urinary incontinence, mainly urge incontinence (47% of patients), and urgency
      frequency (34% of patients) improved at 6 months and end of follow-up, but not
      retention and dysuria. Specific quality of life was improved for fecal and
      urinary incontinence at 6 months and end of follow-up. At the end of follow-up,
      73% patients were highly satisfied with the technique, but 9% felt their
      condition had deteriorated. The reoperation rate was 29%, of which 12% were
      indicated because of a complication. LIMITATIONS: This study was limited by its
      retrospective nature and the multiple causes of incontinence. CONCLUSION: Fecal
      and urinary incontinence, studied by symptoms scores and specific quality-of-life
      scores, are improved in patients receiving sacral nerve stimulation for double
      incontinence.

PMID- 23135588
TI  - Electrical stimulation of anal sphincter or pudendal nerve improves anal
      sphincter pressure.
AB  - OBJECTIVE: Stimulation of the pudendal nerve or the anal sphincter could provide
      therapeutic options for fecal incontinence with little involvement of other
      organs. The goal of this project was to assess the effects of pudendal nerve and
      anal sphincter stimulation on bladder and anal pressures. DESIGN: Ten virgin
      female Sprague Dawley rats were randomly allocated to control (n = 2), perianal
      stimulation (n = 4), and pudendal nerve stimulation (n = 4) groups. A monopolar
      electrode was hooked to the pudendal nerve or placed on the anal sphincter.
      Aballoon catheter was inserted into the anus to measure anal pressure, and a
      catheter was inserted into the bladder via the urethra to measure bladder
      pressure. Bladder and anal pressures were measured with different electrical
      stimulation parameters and different timing of electrical stimulation relative to
      spontaneous anal sphincter contractions. RESULTS: Increasing stimulation current
      had the most dramatic effect on both anal and bladder pressures. An immediate
      increase in anal pressure was observed when stimulating either the anal sphincter
      or the pudendal nerve at stimulation values of 1 mA or 2 mA. No increase in anal
      pressure was observed for lower current values. Bladder pressure increased at
      high current during anal sphincter stimulation, but not as much as during
      pudendal nerve stimulation. Increased bladder pressure during anal sphincter
      stimulation was due to contraction of the abdominal muscles. CONCLUSION:
      Electrical stimulation caused an increase in anal pressures with bladder
      involvement only at high current. These initial results suggest that electrical
      stimulation can increase anal sphincter pressure, enhancing continence control.

PMID- 23135589
TI  - Single-access laparoscopic colectomy utilizing gravity in the lateral decubitus
      position.
AB  - BACKGROUND: Only a limited number of instruments can be used in single-access
      laparoscopic colectomy, and triangulation must be forfeited to avoid instrument
      collision. We investigated whether this problem could be overcome by performing
      laparoscopic colectomy by the use of the lateral decubitus position, making full
      use of gravity. OBJECTIVE: The aim of this study was to determine whether single
      access laparoscopic colectomy could be achieved while maintaining patients in the
      lateral decubitus position. DESIGN: This was a prospective study. SETTING: This
      single-center study was conducted in a hospital. PATIENTS: Ten consecutive
      patients (4 men and 6 women) with stage II or III colon cancer were included.
      INTERVENTIONS: Each patient was placed in the lateral decubitus position. Single
      port access to the abdomen was provided by a 3.0-cm incision at the umbilicus.
      The roots of the supplying or draining vessels were isolated and divided for
      lymphadenectomy. Next, the colon was dissected from a lateral approach, without
      the help of the assistant. The specimen was extracted from the single-access
      incision. Extracorporeal or intracorporeal anastomosis was performed. MAIN
      OUTCOME MEASURES: The primary outcome measured was the feasibility of single
      access laparoscopic colectomy in the lateral decubitus position. RESULTS: There
      were no intraoperative complications and no need for conversions to conventional
      laparoscopic surgery, open surgery, or the supine position. The median total
      surgical time was 154 minutes (interquartile range, 135-220 minutes). Surgical
      blood loss was slight (<20 mL) in all patients. No postoperative complications
      occurred. The median postoperative hospital stay was 7 days (interquartile range,
      5-7 days). LIMITATIONS: The sample size was small. CONCLUSIONS: Our results show
      that single-access laparoscopic colectomy in the lateral decubitus position is
      safe and feasible.

PMID- 23135590
TI  - Learning curve and case selection in laparoscopic colorectal surgery:  systematic
      review and international multicenter analysis of 4852 cases.
AB  - BACKGROUND: The learning curve for laparoscopic colorectal surgery has not been
      conclusively analyzed. No reliable framework for case selection during training
      is available. OBJECTIVE: The aim of this study was to analyze the length of the
      learning curve of laparoscopic colorectal surgeons and to recommend a case
      selection framework at the early stage of independent practice. DATA SOURCES:
      Medline (1988-2010, October week 4) and Embase (1988-2010) were used for the
      literature review, databases were retrieved from the authors, and expert opinion
      was surveyed. STUDY SELECTION: Studies describing the learning curve of
      laparoscopic or laparoscopically assisted colorectal surgery were selected.
      INTERVENTION: No interventions were performed. MAIN OUTCOME MEASURES: Learning
      curves were analyzed by using risk-adjusted, bootstrapped cumulative sum curves.
      Conversions and complications were independent variables in a multilevel random
      effects regression model. Recommendations are based on analysis of ORs and a
      structured expert opinion gauging process. RESULTS: Twenty-three studies were
      identified, showing great disparity on the length of the learning curve. Seven
      studies, representing 4852 cases (19 surgeons), were analyzed. Risk-adjusted
      cumulative sum charts demonstrated the length of the learning curves to be 152
      cases for conversions, 143 for complications, 96 for operating time, 87 for blood
      loss, and 103 for length of stay. Body mass index and pelvic dissection (rectum),
      especially in male patients, independently increased the risk of complication and
      conversion. The expert survey revealed that increasing T stage and complicated
      inflammatory disease are likely to increase the complexity of the case. Based on
      this evidence, a framework for case selection in training was proposed.
      LIMITATIONS: The generalizability of the study results maybe reduced because of
      inconsistent data quality and individual variations in the length of the learning
      curve CONCLUSIONS: This multicenter database suggests a length of the learning
      curve of 88 to 152 cases. The use of the suggested framework may prevent high
      conversion and complication rates during the learning curve.

PMID- 23135592
TI  - Sigmoidectomy syndrome? Patients' perspectives on the functional outcomes
      following surgery for diverticulitis.

PMID- 23135594
TI  - Ligation of the descending branch of the left colic artery to increase colon
      length in low-tie ligation.

PMID- 23135596
TI  - Is metachronous colorectal cancer really metachronous?

PMID- 23135597
TI  - Strictureplasty or resection for small-bowel Crohn's disease?

PMID- 23135598
TI  - Self-assessment quiz: Answers, critiques, and references.

PMID- 23135603
TI  - Effects of elevated peroxidase levels and corn earworm feeding on gene expression
      in tomato.
AB  - Microarray analysis was used to measure the impact of herbivory by Helicoverpa
      zea, (corn earworm caterpillar) on wild-type and transgenic tomato, Solanum
      lycopersicum, plants that over-express peroxidase. Caterpillar herbivory had by
      far the greatest affect on gene expression, but the peroxidase transgene also
      altered the expression of a substantial number of tomato genes. Particularly high
      peroxidase activity resulted in the up-regulation of genes encoding proteinase
      inhibitors, pathogenesis-related (PR) proteins, as well as proteins associated
      with iron and calcium transport, and flowering. In a separate experiment
      conducted under similar conditions, real-time quantitative polymerase chain
      reaction (qPCR) analysis confirmed our microarray results for many genes. There
      was some indication that multiple regulatory interactions occurred due to the
      interaction of the different treatments. While herbivory had the greatest impact
      on tomato gene expression, our results suggest that levels of expression of a
      multifunctional gene, such as peroxidase and its products, can influence other
      gene expression systems distinct from conventional signaling pathways, further
      indicating the complexity of plant defensive responses to insects.

PMID- 23135604
TI  - Significant reduction of ATP production in PHA-activated CD4+ cells in 1-day-old
      blood from transplant patients.
AB  - BACKGROUND: Global immunosuppression can be measured by assessing adenosine
      triphospate (ATP) levels in mitogen-stimulated CD4+ T cells. METHODS: We
      investigated the effect of storage time on ATP levels in 234 blood samples from
      18 healthy individuals and 152 transplant patients. The difference between day 0
      (<13 hours post-blood draw) and day 1 (24-37 hours) measurements was analyzed and
      compared with various factors; a subset of samples was also analyzed in 6-hour
      intervals. RESULTS: The ATP levels were significantly lower on day 1 compared
      with that on day 0 in healthy individuals (279+/-159 vs 414+/-159 ng/mL, P<0.001)
      and patients (356+/-209 vs 455+/-221 ng/mL, P<0.0001). Of the 18 healthy
      individuals, 17 showed ATP reduction, whereas 192 (89%) of 216 patients did so on
      day 1 (24.8+/-24.1%). In the time course analysis, ATP levels decreased with the
      blood storage time in healthy and patient samples, and the reduction began as
      early as 7 hours post-blood draw. The reduction rate was significantly higher in
      patient samples with low day 0 ATP levels compared with samples with moderate or
      high levels (44.7+/-31.3% vs 23.2+/-23.6% or 18.7+/-15.7%; P<0.001). The
      reduction rate in patients treated with alemtuzumab induction was slightly higher
      than that in daclizumab-treated patients (28.8+/-24.6% vs 21.3+/-21.3%, P=0.09).
      CD4+ cell number did not change within 24 hours post-blood draw, but CD4
      expression decreased 2.0+/-2.8% (P<0.05). CONCLUSIONS: The ATP levels are
      significantly lower in 1-day-old blood compared with fresh blood, suggesting that
      fresh blood should be used for assessing the T cell immune function to obtain the
      most accurate results.

PMID- 23135605
TI  - Dose-related effects of salvinorin A in humans: dissociative, hallucinogenic, and
      memory effects.
AB  - RATIONALE: Salvinorin A is a kappa opioid agonist and the principal psychoactive
      constituent of the plant Salvia divinorum, which has increased in popularity as a
      recreational drug over the past decade. Few human studies have examined
      salvinorin A. OBJECTIVE: This double-blind, placebo-controlled study evaluated
      the dose-related effects of inhaled salvinorin A in individuals with histories of
      hallucinogen use. METHODS: Eight healthy hallucinogen-using adults inhaled up to
      16 doses of salvinorin A (0.375-21 MUg/kg) in ascending order. Physiological,
      behavioral, and subjective effects were assessed every 2 min for 60 min after
      administration. Qualitative subjective effects were assessed retrospectively via
      questionnaires at the end of sessions. Persisting effects were assessed 1 month
      later. RESULTS: Orderly dose-related effects peaked at 2 min and then rapidly
      dissipated, replicating previous findings. Subjective effects were intense, with
      maximal drug strength ratings or unresponsiveness frequently observed at high
      doses. Questionnaires assessing qualitative effects (Hallucinogen Rating Scale,
      Pharmacological Class Questionnaire) suggested some overlap with serotonergically
      mediated classic hallucinogens. Salvinorin A also produced dose-related
      dissociative effects and impairments in recall/recognition memory. At 1-month
      follow-up, there was no evidence of persisting adverse effects. Participants
      reported that salvinorin A effects were qualitatively different from other drugs.
      CONCLUSIONS: Salvinorin A produces a unique profile of subjective and cognitive
      effects, including strong dissociative effects and memory impairment, which only
      partially overlap with classic hallucinogen effects. Along with nonhuman studies
      of salvinorin A, these results are important for understanding the neurobiology
      of the kappa opioid system and may ultimately have important therapeutic
      applications.

PMID- 23135607
TI  - The early cardiovascular changes in pediatric patients with systemic lupus
      erythematosus.
AB  - BACKGROUND: In patients with systemic lupus erythematous (SLE) late-onset deaths
      are due to morbid cardiovascular changes (CVCs). Inflammatory and immune-mediated
      mechanisms are involved in promoting atherosclerosis development in SLE that is
      reflected in both functional and morphological changes in the cardiovascular
      system. The aim of our study was to determine the presence of these changes in
      pediatric SLE patients. METHODS: Fifty-one consecutive patients (13 male, 38
      female) with SLE and 25 healthy controls were included in the study. Arterial
      stiffness was assessed by carotid-femoral pulse wave velocity (PWVcf) and
      augmentation index (AIx), as measured by the Vicorder. Carotid intima-media
      thickness (cIMT) and the left ventricular mass index (LVMi) were also determined.
      RESULTS: Patients with SLE, despite equivalent exposure to "traditional"
      cardiovascular risk factors, presented a higher mean PWVcf and AIx than controls
      (6.56 +/- 1.45 vs. 5.29 +/- 0.67 m/s, P =0.01 and 14.7 +/- 8.1 vs. 9.36 +/- 3.59
      %, P = 0.02, respectively). SLE patients had greater values of cIMT and LVMi than
      controls (0.54 +/- 0.06 vs. 0.35 +/- 0.12 mm, P = 0.00 and 32.4 +/- 10.8 vs 28.8
      +/- 1.5, P = 0.01, respectively). Nine patients had left ventricular hypertrophy
      (LVMi >38 g/m(2.7)). There was no significant difference in PWV, AIx, cIMT and
      LVMi values between presence of hypertension or nephritis within SLE patients. We
      found significant correlations between all parameters and activity scores.
      CONCLUSIONS: Our results demonstrate that functional and morphological CVCs are
      independent of traditional risk factors in pediatric SLE patients and correlate
      with SLE disease activity scores in the early disease stages.

PMID- 23135608
TI  - Nephrotic syndrome in an 18-year-old boy with congenital myelomeningocele:
      questions.

PMID- 23135609
TI  - Mitochondrial tRNA(Phe) mutation as a cause of end-stage renal disease in
      childhood.
AB  - BACKGROUND: We identified a mitochondrial tRNA mutation (m.586 G > A) in a
      patient with renal failure and symptoms consistent with a mitochondrial
      cytopathy. This mutation was of unclear significance due to the absence of
      consistent reports of linkage to specific disease phenotypes and any data
      pertaining to its effects on mitochondrial function. CASE-DIAGNOSIS/TREATMENT: A
      16-month-old girl with failure-to-thrive, developmental regression, persistent
      lactic acidosis, hypotonia, gastrointestinal dysmotility, adrenal insufficiency,
      and hematologic abnormalities developed hypertension and renal impairment with
      chronic tubulointerstitial fibrosis, progressing to renal failure with the need
      for peritoneal dialysis. Evaluation of her muscle and blood led to the
      identification of a mutation of the mitochondrial tRNA for phenylalanine, m.586 G
      > A. CONCLUSIONS: The m.586 G > A mutation is pathogenic and a cause of end-stage
      renal disease in childhood. The mutation interferes with the stability of
      tRNA(Phe) and affects the translation of mitochondrial proteins and the stability
      of the electron transport chain.

PMID- 23135610
TI  - (-)-Epigallocatechin 3-gallate inhibits invasion by inducing the expression of
      Raf kinase inhibitor protein in AsPC-1 human pancreatic adenocarcinoma cells
      through the modulation of histone deacetylase activity.
AB  - The aim of the present study was to assess whether (-)-epigallocatechin 3-gallate
      (EGCG) via epigenetic modifications, regulates Raf kinase inhibitor protein
      (RKIP) expression and invasive metastatic activity in AsPC-1 pancreatic
      adenocarcinoma cells. Basal levels of RKIP were examined in various human
      pancreatic cancer cell lines and MTT assay was used to assess cell viability.
      AsPC-1 cells were treated with EGCG with/without trichostatin A (TSA), as the
      positive control, for 24 h. The levels of RKIP and histone H3 induction were
      analyzed by immunoblot analysis. In order to determine the role of RKIP induction
      in NF-kappaB translocation and invasive metastatic activity in AsPC-1 cells, we
      examined NF-kappaB translocation, invasive metastatic parameters by RT-PCR,
      metastasis-related proteins by western blot analysis and matrix metalloproteinase
      (MMP)-2 and -9 activity by gelatin zymography. To validate RKIP induction through
      the extracellular signal regulated kinase (ERK) pathway, the cells were treated
      with U0126, an ERK inhibitor. Our results showed that EGCG induced RKIP
      upregulation via the inhibition of histone deacetylase (HDAC) activity which
      increased histone H3 expression and inhibited Snail expression, NF-kappaB nuclear
      translocation, MMP-2 and -9 activity and Matrigel invasion in AsPC-1 cells. The
      expression of E-cadherin in the cells was upregulated. The phosphorylation of ERK
      was decreased by RKIP induction following EGCG treatment. Furthermore, our
      results confirmed that U0126 treatment repressed ERK phosphorylation and induced
      RKIP expression. Taken together, our results strongly suggest that EGCG regulates
      RKIP/ERK/NF-kappaB and/or RKIP/NF-kappaB/Snail and inhibits invasive metastasis
      in the AsPC-1 human pancreatic adenocarcinoma cell line.

PMID- 23135611
TI  - Donor-acceptor, ferrocenyl substituted BODIPYs with marvelous supramolecular
      interactions.
AB  - A series of donor-acceptor ferrocenyl substituted BODIPYs have been designed and
      synthesized via palladium catalyzed Suzuki and Sonogashira coupling reactions.
      The UV-visible absorption results indicate intramolecular charge transfer from
      the ferrocene to the BODIPY. The fluorescence quantum yield was drastically
      reduced, where the ferrocenyl group was directly attached to the BODIPY. The
      single crystal X-ray structures of 1', 2, 3, and 4 show marvelous supramolecular
      interactions. The crystal structure of 1' shows an extensive hydrogen bonded 2D
      network, 2 shows sheet like structure, 3 shows zigzag packing along the a-axis,
      whereas 4 shows sheet like structure in which both the surfaces of the sheet are
      covered with the ferrocenyl group.

PMID- 23135612
TI  - Primary central nervous system histiocytic sarcoma.
AB  - Histiocytic sarcoma is a rare, lymphohematopoietic malignant neoplasm composed of
      tumor cells showing morphologic and immunophenotypic features of mature tissue
      histiocytes. Involvement of the central nervous system (CNS) as either a part of
      a systemic disease or as a primary lesion has rarely been described so far. We
      present a case of primary CNS histiocytic sarcoma in an adult patient and review
      the literature on this rare entity. 

PMID- 23135613
TI  - Induced psoriasis after rituximab therapy for rheumatoid arthritis: a case report
      and review of the literature.
AB  - Rituximab is a human/murine monoclonal antibody targeting the CD20 antigen on B
      lymphocytes surface. Although it has been licensed for treatment of non-Hodgkin's
      lymphoma, nowadays it is also a novel therapy for autoimmune diseases, such as
      rheumatoid arthritis and systemic lupus erythematosus. Despite the increasing
      evidence regarding the safety and efficacy of rituximab in these conditions, many
      cutaneous adverse events have been reported. Here, we describe the case of a 69
      year-old patient, affected by rheumatoid arthritis, who developed psoriatic
      lesions on her trunk and arms, three months after the second course of rituximab.
      Similar cases appearing in the literature will also be briefly mentioned. 

PMID- 23135614
TI  - Near-infrared luminescent cubic silicon carbide nanocrystals for in vivo
      biomarker applications: an ab initio study.
AB  - Molecule-sized fluorescent emitters are much sought-after to probe biomolecules
      in living cells. We demonstrate here by time-dependent density functional
      calculations that the experimentally achievable 1-2 nm sized silicon carbide
      nanocrystals can emit light in the near-infrared region after introducing
      appropriate color centers in them. These near-infrared luminescent silicon
      carbide nanocrystals may act as ideal fluorophores for in vivo bioimaging.

PMID- 23135615
TI  - Carotid stenosis assessment with multi-detector CT angiography: comparison
      between manual and automatic segmentation methods.
AB  - Luminal stenosis is used for selecting the optimal management strategy for
      patients with carotid artery disease. The aim of this study is to evaluate the
      reproducibility of carotid stenosis quantification using manual and automated
      segmentation methods using submillimeter through-plane resolution Multi-Detector
      CT angiography (MDCTA). 35 patients having carotid artery disease with >30 %
      luminal stenosis as identified by carotid duplex imaging underwent contrast
      enhanced MDCTA. Two experienced CT readers quantified carotid stenosis from axial
      source images, reconstructed maximum intensity projection (MIP) and 3D-carotid
      geometry which was automatically segmented by an open-source toolkit (Vascular
      Modelling Toolkit, VMTK) using NASCET criteria. Good agreement among the
      measurement using axial images, MIP and automatic segmentation was observed.
      Automatic segmentation methods show better inter-observer agreement between the
      readers (intra-class correlation coefficient (ICC): 0.99 for diameter stenosis
      measurement) than manual measurement of axial (ICC = 0.82) and MIP (ICC = 0.86)
      images. Carotid stenosis quantification using an automatic segmentation method
      has higher reproducibility compared with manual methods.

PMID- 23135616
TI  - STARR: a speech test for evaluation of the effectiveness of auditory prostheses
      under realistic conditions.
AB  - OBJECTIVES: The objective was to develop and evaluate a new sentence test, the
      Sentence Test with Adaptive Randomized Roving levels, intended to emulate
      everyday listening experience, using both normal-hearing (NH) and cochlear
      implant (CI) groups, examining practicality, learning, test-retest variability,
      and interlist variability. DESIGN: In experiment 1, each of 25 NH adults was
      tested using five lists, each comprising 30 sentences. One male and one female
      speaker each spoke 15 sentences. Ten sentences were presented at each of three
      presentation levels: 50, 65, and 80 dB SPL. The relative level of a speech-shaped
      noise was varied adaptively to estimate the speech reception threshold (SRT).
      Counterbalance for list order was achieved by staggering the allocation of lists
      to participants. To allow assessment of learning effects, no practice was given.
      The variability of mean SRTs across lists was small, but correction factors were
      derived for each list so that, after correction, all lists gave the same mean
      SRT. Test-retest variability was estimated by examining the corrected SRTs for
      each subject's five lists. In experiment 2, 25 CI users each received one test
      list after a small amount of practice. Experiment 3 examined the effect of speech
      rate using time-compressed speech, for age-matched NH and CI users. RESULTS: The
      mean SRT for the NH participants was approximately -6 dB and was similar for the
      male and female speakers. There was a small but significant improvement in SRTs
      between the first and later lists administered, but no further improvement for
      subsequent lists. On the basis of the variability of the corrected SRTs within
      each participant, a 2.2 dB difference in SRT is meaningful for comparisons using
      one test list per condition, for a single participant. The percentage of key
      words correct varied with presentation level over a 13% range, being best at 65
      dB SPL. Only 40% of the CI group achieved an SRT lower than 20 dB for both
      speakers. There was large individual variability in the SRTs, and SRTs were
      higher for the female than for the male speaker. For the CI participants, the
      percentage of key words correct varied markedly with level, from 19% at the
      lowest level to 57% at the medium level. Time compression had a small effect for
      NH participants but a very large effect for CI participants. CONCLUSIONS: The
      Sentence Test with Adaptive Randomized Roving levels seems practical to
      administer and is reasonably sensitive. For NH participants, a 2.2 dB difference
      in SRT is meaningful for a single list per condition and a single participant.
      Although learning effects were small for NH participants, it seems prudent to
      provide some practice sentences when testing hearing-impaired or CI participants.
      The very large effect of time compression for the CI group has implications for
      live voice testing of children, because speech rate is only poorly controlled in
      such testing.

PMID- 23135617
TI  - Aging and the perception of temporally interleaved words.
AB  - OBJECTIVE: The purpose of this study was to examine differences between older and
      younger listeners in the ability to sequentially attend to and ignore words.
      DESIGN: Participants (n = 13 older adults and 13 younger adults) completed a
      temporally interleaved word recognition task. On each trial, 10 words were
      presented, and participants were instructed to repeat back every other word while
      ignoring the intervening words. Three variables were examined: (1) whether the
      word strings that were to be attended and to be ignored created syntactically
      correct sentences; (2) whether the to-be-attended and to-be-ignored words were
      presented from the same or from different spatial locations; and (3) whether the
      five target words in each trial (and the five distractor words in each trial)
      were spoken by a single talker or by five different talkers. In addition, digit
      span forward and digit-span backward were measured and used as variables in
      correlation analyses. RESULTS: As a group, the younger participants outperformed
      the older listeners, particularly when the to-be-attended and to-be-ignored words
      were presented from the same spatial location (versus when they were presented
      with spatial separation). Compared with the younger participants, older listeners
      also made more error responses that were to-be-ignored words, although the
      proportion of errors that were not responses involving masking words did not
      significantly differ between groups. Scores on the digit-span-forward test (but
      not digit-span-backward scores or the degree of hearing loss) were associated
      with older individuals' performance on this temporally interleaved speech
      recognition task. CONCLUSIONS: The overall pattern of results suggests that
      factors other than threshold elevation contribute to speech-understanding
      problems experienced by older listeners. However, although younger adults
      outperformed older listeners on this interleaved sentence task, older and younger
      adults benefited, to a similar extent, from spatial separation of the to-be
      attended and to-be-ignored words, and from having a consistent target talker
      within a trial.

PMID- 23135621
TI  - Is there a link between genome-wide hypomethylation in blood and cancer risk?
AB  - Cancer cells display widespread genetic and epigenetic abnormalities, but the
      contribution to disease risk, particularly in normal tissue before disease, is
      not yet established. Genome-wide hypomethylation occurs frequently in tumors and
      may facilitate chromosome instability, aberrant transcription and transposable
      elements reactivation. Several epidemiologic case-control studies have reported
      genomic hypomethylation in peripheral blood of cancer patients, suggesting a
      systemic effect of hypomethylation on disease predisposition, which may be
      exploited for biomarker development. However, more recent studies have failed to
      reproduce this. Here, we report a meta-analysis, indicating a consistent inverse
      association between genomic 5-methylcytosine levels and cancer risk [95%
      confidence interval (CI), 1.2-6.1], but no overall risk association for studies
      using surrogates for genomic methylation, including methylation at the LINE-1
      repetitive element (95% CI, 0.8-1.7). However, studies have been highly
      heterogeneous in terms of experimental design, assay type, and analytical
      methods. We discuss the limitations of the current approaches, including the low
      interindividual variability of surrogate assays such as LINE1 and the importance
      of using prospective studies to investigate DNA methylation in disease risk.
      Insights into genomic location of hypomethylation, from recent whole genome, high
      resolution methylome maps, will help address this interesting and clinically
      important question.

PMID- 23135622
TI  - The expression and functional characterization associated with cell apoptosis and
      proteomic analysis of the novel gene MLAA-34 in U937 cells.
AB  - MLAA-34 is a novel acute monocytic leukemia (M5)-associated antigen (MLAA) that
      plays a role in the apoptosis of U937 cells. However, the expression and
      molecular mechanism of MLAA-34 in U937 cells remain largely unclear. Here, we
      utilized three strategies to gain insight into the expression and molecular
      functions of MLAA-34 and to identify its interacting proteins and pathways
      involved in the fine-tuning of the MLAA-34 response. Western blot analysis was
      performed to assess the expression of MLAA-34 in 41 cell lines and five mixed
      cell types, which revealed that MLAA-34 is most strongly expressed in U937 cells.
      Immunostaining indicated that MLAA-34 is localized in the cytoplasm and cell
      membrane. Furthermore, lentivirus-mediated overexpression of MLAA-34 in the U937
      cell line led to significant suppression of apoptosis and increased the potential
      of tumorigenicity. Co-immunoprecipitation (Co-IP), shotgun and bioinformatic
      analysis identified 256 proteins and 225 of them were annotated by gene ontology
      categories. This analysis revealed 71 proteins involved in cell apoptosis or
      proliferation of biological processes and signaling pathways. Moreover, the
      effect of MLAA-34 apoptosis may be through interaction with the Ras, Wnt, calcium
      and chemokine signaling pathways and thirteen of the annotated proteins may
      interact with MLAA-34 and participate in carcinogenesis directly. This study
      provides a basis for a better understanding of the molecular mechanism and
      proteomics in the inhibition of apoptosis by MLAA-34 in U937 cells and indicates
      that MLAA-34 may be a potential candidate for the early diagnosis and therapeutic
      application of M5.

PMID- 23135623
TI  - A novel, selective, and extremely responsive thienyl-based dual fluorogenic probe
      for tandem superoxide and Hg2+ chemosensing.
AB  - Novel, high "turn-on" Hg(2+) and O(2)(-) fluorescence behaviour (~25-fold) with
      probes bearing [S(thi)N(py)] and [S(thi)N(py)N(py)] binding receptors, joined by
      oxidizable sulphides, may involve S-bound transient ROS species; such optical
      O(2)(-) behaviour operates moderately in neuroblastoma.

PMID- 23135624
TI  - The effect of breastfeeding on neuro-development in infancy.
AB  - The present study examines whether breastfeeding is associated with neuro
      developmental advantages at 9 months of age on a standardised measure of infant
      development in a large cohort study of Irish children. It is hypothesised that if
      breast-milk confers an independent benefit, infants who were never breastfed will
      have reached fewer developmental milestones than those who were partially or
      exclusively breastfed, after controlling for putative confounding variables.
      Families with infants aged 9-months were recruited as part of a nationally
      representative sample for the birth cohort of the Growing Up in Ireland study (n
      = 11,134). Information was collected from mothers on breastfeeding practices,
      socio-demographic characteristics and developmental progress during a household
      interview. Parent-report items on development covered communication, gross motor,
      fine motor, problem solving and personal-social skills. Analysis of pass/fail
      status in each developmental domain using binary logistic regression showed a
      positive effect of any breastfeeding on gross motor, fine motor, problem solving
      and personal-social skills (but not communication) and these remained after
      adjustment for a range of confounding variables. There was, however, little
      evidence of a dose-response effect or advantage of exclusive over partial
      breastfeeding. A clear advantage of breastfeeding on infant development was
      demonstrated. However, the lack of a dose-response association on pass rates
      suggests that the breastfeeding effect may be confounded by other unobserved
      factors or that there is a critical threshold during which time the effect of
      breast milk may be particularly salient for bolstering brain development. 

PMID- 23135625
TI  - Nature or nurture: a systematic review of the effect of socio-economic status on
      the developmental and cognitive outcomes of children born preterm.
AB  - The effect of socio-economic status (SES) on the cognitive outcome of preterm
      born children is unknown. The objectives of this study were to systematically
      review the published literature and to report the strength and consistency of the
      effect of SES on the cognitive outcomes of preterm children, across different SES
      indicators. We conducted a literature search on MEDLINE, EMBASE, PsycINFO and
      Social Science Citation Index to identify English-language cohort or case-control
      studies published after 1990 that had reported the effect of at least one SES
      indicator on cognitive outcome in children born <37 weeks gestation. Fifteen
      studies (from a total 4,162 identified) were included. Thirteen SES indicators
      were evaluated [categorized as: "individual-level" (6 indicators), "family
      structure" (3), "contextual" (2) and "composite" (2)]. Maternal educational level
      was the most frequently evaluated SES indicator (by 11/15 studies) and was most
      consistently associated with cognitive outcome. Maternal education below high
      school level was associated with severe cognitive deficiency [reported odds
      ratios (95 % CI) range: OR = 1.4 (1.0-1.9) to OR = 2.3 (1.2-4.5)]. A meta
      analytic measure of the effect of SES was not calculated due to heterogeneity in
      studies. SES appears to confound the association between preterm birth and
      cognitive deficit and should be adjusted for in studies reporting cognitive
      outcome. 

PMID- 23135626
TI  - Physician attitudes toward over the counter availability for oral contraceptives.
AB  - To assess physician attitude towards making oral contraceptives available over
      the counter in the United States (US). We assessed physician attitudes towards a
      transition from prescription only to over-the-counter availability (rx-OTC) for
      oral contraceptive pills by disseminating an electronic survey directed primarily
      to residents training in Obstetrics and Gynecology (OBGYN) and Family Practice in
      the US. An overwhelming majority of 638 respondents (71 %) were against an rx-OTC
      switch for combined oral contraceptives and among this subset of respondents the
      primary concern was safety (92.3 %). Overall, respondents were evenly divided on
      the issue of an rx-OTC switch for progestin-only-pills but of those who opposed,
      73.2 % cited safety as their primary concern. For progestin-only-pills female
      respondents were more likely to support OTC availability. Most OBGYN and Family
      Practice residents opposed to OTC availability for oral contraceptives cite
      safety as their primary concern. Considering the abundant evidence as to the
      overall safety of oral contraceptives, especially progestin-only-pills, there
      appears to be a knowledge deficit among OBGYN and Family Practice residents
      regarding the safety of oral contraceptives.

PMID- 23135627
TI  - Normalization procedures and reference material selection in stable HCNOS isotope
      analyses: an overview.
AB  - The uncertainties of stable isotope results depend not only on the technical
      aspects of measurements, but also on how raw data are normalized to one of the
      international isotope scales. The inconsistency in the normalization methods used
      and in the selection of standards may lead to substantial differences in the
      results obtained. Therefore, unification of the data processing protocols
      employed is highly desirable. The best performing methods are two-point or
      multipoint normalization methods based on linear regression. Linear regression is
      most robust when based on standards that cover the entire range of delta values
      typically observed in nature, regardless of the delta values of the samples
      analysed. The uncertainty can be reduced by 50 % if measurements of two different
      standards are performed four times, or measurements of four standards are
      performed twice, with each batch of samples. Chemical matrix matching between
      standards and samples seems to be critical for delta (18)O of nitrate or delta
      (2)H of hair samples (thermal conversion/elemental analyser), for example;
      however, it is not necessarily always critical for all types of samples and
      techniques (e.g. not for most delta (15)N and delta (13)C elemental analyser
      analyses). To ensure that all published data can be recalculated, if delta values
      of standards or the isotope scales are to be updated, the details of the
      normalization technique and the delta values of the standards used should always
      be clearly reported.

PMID- 23135628
TI  - Expression of pyruvate dehydrogenase kinase-1 in gastric cancer as a potential
      therapeutic target.
AB  - In contrast to mitochondria in healthy cells, which utilize oxidative
      phosphorylation, malignant cells undergo elevated glycolysis for energy
      production using glucose. The objectives of this study were to evaluate whether
      the expression of various molecules, including pyruvate dehydrogenase kinase-1
      (PDK-1), is involved in the altered glucose metabolism associated with gastric
      cancer prognosis and to assess the role of a therapeutic agent in targeting
      glucose metabolism in gastric cancer. Immunohistochemistry was performed on
      gastric cancer tissues obtained from 152 patients who underwent curative
      resection to assess the expression of hypoxia-inducible factor-1alpha (HIF
      1alpha), glucose transporter-1 (GLUT-1), hexokinase-2 (HK-2) and PDK-1. In an in
      vitro analysis, the lactate production and glucose uptake levels, cellular
      viability and 5-fluorouracil (5-FU) responses were evaluated before and after
      treatment with dichloroacetate (DCA), a PDK-1 inhibitor, in the MKN45 and AGS
      gastric cancer cell lines and in the non-cancerous HEK293 cell line. GLUT-1 and
      PDK-1 expression was significantly associated with tumor progression, although
      only PDK-1 expression was an independent prognostic factor for patients who
      received 5-FU adjuvant treatment. There was no significant difference in cell
      viability between the HEK293 and gastric cancer cell lines following DCA
      treatment. However, DCA treatment reduced lactate production and increased
      responsiveness to 5-FU in MKN45 cells, which expressed high levels of PDK-1 in
      comparison to the other cell lines. Thus, PDK-1 may serve as a biomarker of poor
      prognosis in patients with gastric cancer. In addition, PDK-1 inhibitors such as
      DCA may be considered an additional treatment option for patients with PDK-1
      expressing gastric cancers.

PMID- 23135629
TI  - Urinary schistosomiasis in asylum seekers in Italy: an emergency currently
      undervalued.
AB  - Despite schistosomiasis is one of the most prevalent tropical diseases in
      developing countries and and large flows of migrants come from countries where
      the disease is endemic, imported urinary schistosomiasis is still not easily
      recognized in non-endemic areas, especially if not subjected to specific
      investigations. Moreover schistosomiasis is currently not reportable in any
      European public health system. The data presented in this report were collected
      were collected between asylum seekers by a simple screening method based on a
      prior or actual history of a macroscopic hematauria. In case of a history of
      gross hematuria, the patient underwent to specific exams standardized for the
      diagnosis of urinary schistosomiasis. Our data show that the prevalence of the
      disease has been largely underestimated by European Surveillance Systems; in fact
      in a small population of young asylum seekers coming from endemic areas for
      schistosomiasis, we found a significant number of individuals with symptomatic
      disease. Given that the disease typically has an insidious course, it is highly
      probable that a screening procedure is able to identify early asymptomatic or
      mildly symptomatic subjects and avoid the serious complications that are present
      in advanced stages of disease. Given the limits and the costs of a late diagnosis
      and that an effective treatment is available, subjects from endemic areas should
      be actively screened for urinary schistosomiasis. 

PMID- 23135630
TI  - Effects of Taraxacum officinale on fatigue and immunological parameters in mice.
AB  - In Korean herbal medicine dandelion (Taraxacum officinale, TO) has been used to
      improve energy levels and health. However, the effects of TO in experimental
      models remain unclear. We examined the anti-fatigue and immune-enhancing effects
      of TO in mice by performing a forced swimming test (FST) and in vitro by using
      peritoneal macrophages, respectively. After daily oral administration of TO,
      blood biochemical parameters related to fatigue were measured after the FST. FST
      immobility time was significantly decreased in the TO-treated group (100 mg/kg)
      on the tenth day. TO (10 and 100 mg/kg) treatment significantly increased glucose
      levels, acting as an energy source. The level of lactic dehydrogenase, which is
      an accurate indicator of muscle damage, tended to decline after TO administration
      (10 and 100 mg/kg). When TO (100 mg/kg) was orally administered to mice, blood
      urea nitrogen levels decreased significantly. We also examined the effect of TO
      on the production of cytokines and nitric oxide (NO) in mouse peritoneal
      macrophages. When TO was used in combination with recombinant interferon-gamma
      (rIFN-&#947;), a noticeable cooperative induction of tumor necrosis factor-alpha
      (TNF-&#945;), interleukin  (IL)-12p70, and IL-10 production was observed.
      Furthermore, in peritoneal macrophages, rIFN-&#947; plus TO treatment
      significantly increased the production of NO through inducible  nitric oxide
      synthase (iNOS) induction. Taken together, these results suggest that TO improves
      fatigue-related indicators and immunological parameters in mice.

PMID- 23135631
TI  - Radioiodination of aryl-alkyl cyclic sulfates.
AB  - Among the currently available positron emitters suitable for Positron Emission
      Tomography (PET), (124)I has the longest physical half-life (4.2 days). The long
      half-life and well-investigated behavior of iodine in vivo makes (124)I very
      attractive for pharmacological studies. In this communication, we describe a
      simple yet effective method for the synthesis of novel (124)I labeled compounds
      intended for PET imaging of arylsulfatase activity in vivo. Arylsulfatases have
      important biological functions, and genetic deficiencies of such functions
      require pharmacological replacement, the efficacy of which must be properly and
      non-invasively evaluated. These enzymes, even though their natural substrates are
      mostly of aliphatic nature, hydrolyze phenolic sulfates to phenol and sulfuric
      acid. The availability of [(124)I]iodinated substrates is expected to provide a
      PET-based method for measuring their activity in vivo. The currently available
      methods of synthesis of iodinated arylsulfates usually require either introducing
      of a protected sulfate ester early in the synthesis or introduction of sulfate
      group at the end of synthesis in a separate step. The described method gives the
      desired product in one step from an aryl-alkyl cyclic sulfate. When treated with
      iodide, the source cyclic sulfate opens with substitution of iodide at the alkyl
      center and gives the desired arylsulfate monoester.

PMID- 23135633
TI  - Abstracts of the 2012 World Molecular Imaging Congress. Dublin, Ireland.
      September 5-8, 2012.

PMID- 23135634
TI  - [Injection techniques in the cervical spine].
AB  - Spinal injections are a treatment option in the conservative management of
      degenerative spinal disorders. The indications must be critically reviewed for
      every patient. Treatment with injections for painful spinal disorders should be a
      part of interdisciplinary treatment regimes. The diagnostic value varies between
      injection procedures. A large number of imaging techniques are used to achieve a
      precise and safe needle placement in interventional procedures. The following
      article presents an overview of common fluoroscopy-guided spinal injection
      techniques for the cervical spine.

PMID- 23135632
TI  - Synthesis, antioxidant and antimicrobial activity of a  new phloridzin derivative
      for dermo-cosmetic applications.
AB  - The phenolic compound phloridzin (phloretin 2&#8242;-O-glucoside, variously named
      phlorizin, phlorrhizin, phlorhizin or phlorizoside) is a prominent member of the
      chemical class of dihydrochalcones, which are phenylpropanoids. Phloridzin is
      specifically found in apple and apple juice and known for its biological
      properties. In particular we were attracted by potential dermo-cosmetic
      applications. Here we report the synthesis, stability studies and antimicrobial
      activity of compound F2, a new semi-synthetic derivative of phloridzin. The new
      derivative was also included in finished formulations to evaluate its stability
      with a view to a potential topical use. Stability studies were performed by HPLC;
      PCL assay and ORAC tests were used to determine the antioxidant activity. F2
      presented an antioxidant activity very close to that of the parent phloridzin,
      but, unlike the latter, was more stable in formulations. To further explore
      potential health claims, antifungal activity of phloridzin and its derivative F2
      were determined; the results, however, were rather low; the highest value was
      31,6% of inhibition reached by F2 on Microsporum canis at the highest dose.

PMID- 23135635
TI  - Quantitative analyses of postmortem heat shock protein mRNA profiles in the
      occipital lobes of human cerebral cortices: implications in cause of death.
AB  - Quantitative RNA analyses of autopsy materials to diagnose the cause and
      mechanism of death are challenging tasks in the field of forensic molecular
      pathology. Alterations in mRNA profiles can be induced by cellular stress
      responses during supravital reactions as well as by lethal insults at the time of
      death. Here, we demonstrate that several gene transcripts encoding heat shock
      proteins (HSPs), a gene family primarily responsible for cellular stress
      responses, can be differentially expressed in the occipital region of postmortem
      human cerebral cortices with regard to the cause of death. HSPA2 mRNA levels were
      higher in subjects who died due to mechanical asphyxiation (ASP), compared with
      those who died by traumatic injury (TI). By contrast, HSPA7 and A13 gene
      transcripts were much higher in the TI group than in the ASP and sudden cardiac
      death (SCD) groups. More importantly, relative abundances between such HSP mRNA
      species exhibit a stronger correlation to, and thus provide more discriminative
      information on, the death process than does routine normalization to a
      housekeeping gene. Therefore, the present study proposes alterations in HSP mRNA
      composition in the occipital lobe as potential forensic biological markers, which
      may implicate the cause and process of death.

PMID- 23135637
TI  - Palladium-catalyzed asymmetric Heck arylation of 2,3-dihydrofuran--effect of
      prolinate salts.
AB  - Chiral ionic liquids (CILs) containing L-prolinate and L-lactate anions and non
      chiral quaternary ammonium cations were employed in the palladium catalyzed
      enantioselective Heck arylation of 2,3-dihydrofuran with aryl iodides
      (iodobenzene, 4-iodotoluene, 2-iodoanisole, 4-iodoanisole, 4-iodoacetophenone).
      In all the reactions 2-aryl-2,3-dihydrofuran (3) was obtained as the main product
      with the yield up to 52% at the total conversion reaching 83%. Product 3, 2
      phenyl-2,3-dihydrofuran, was obtained with excellent enantioselectivity (>99% ee)
      in a 6 h reaction with tetrabutylammonium L-prolinate. In the proposed
      homogeneous reaction Pd(0) nanoparticles are considered as a resting state of the
      catalyst and a source of soluble palladium species catalyzing the Heck reaction.
      The yield and stereoselectivity of the Heck reaction are strongly influenced by
      the kind of non-chiral cations present in CILs.

PMID- 23135636
TI  - Impact of retrotransposons in pluripotent stem cells.
AB  - Retrotransposons, which constitute approximately 40% of the human genome, have
      the capacity to 'jump' across the genome. Their mobility contributes to
      oncogenesis, evolution, and genomic plasticity of the host genome. Induced
      pluripotent stem cells as well as embryonic stem cells are more susceptible than
      differentiated cells to genomic aberrations including insertion, deletion and
      duplication. Recent studies have revealed specific behaviors of retrotransposons
      in pluripotent cells. Here, we review recent progress in understanding
      retrotransposons and provide a perspective on the relationship between
      retrotransposons and genomic variation in pluripotent stem cells.

PMID- 23135638
TI  - Pearls are novel Cajal body-like structures in the Xenopus germinal vesicle that
      are dependent on RNA pol III transcription.
AB  - We have identified novel nuclear bodies, which we call pearls, in the giant
      oocyte nuclei of Xenopus laevis and Xenopus tropicalis. Pearls are attached to
      the lampbrush chromosomes at specific loci that are transcribed by RNA polymerase
      III, and they disappear after inhibition of polymerase III activity. Pearls are
      enriched for small Cajal body-specific RNAs (scaRNAs), which are guide RNAs that
      modify specific nucleotides on splicing snRNAs. Surprisingly, snRNAs themselves
      are not present in pearls, suggesting that pearls are not functionally equivalent
      to Cajal bodies in other systems, which contain both snRNAs and scaRNAs. We
      suggest that pearls may function in the processing of RNA polymerase III
      transcripts, such as tRNA, 5S rRNA, and other short non-coding RNAs.

PMID- 23135639
TI  - Effect of minimizing tension during robotic-assisted laparoscopic radical
      prostatectomy on urinary function recovery.
AB  - OBJECTIVES: Although most prostatectomy studies emphasize optimal nerve-sparing
      dissection planes, subtle technical variation also affects functional outcomes.
      The impact of minimizing assistant/surgeon tension on urinary function has not
      been quantified. We assess urinary function after attenuating neurovascular
      bundle (NVB) and rhabdosphincter tension during robotic-assisted radical
      prostatectomy (RARP). METHODS: Retrospective study of prospectively collected
      data for 268 (RARP-T) versus 342 (RARP-0T) men with versus without tension on the
      NVB and rhabdosphincter during RARP. Outcomes compared include Expanded Prostate
      Cancer Index (EPIC) urinary function, estimated blood loss (EBL), operative time,
      and positive surgical margins (PSM). RESULTS: In unadjusted analysis, men
      undergoing RARP-T versus RARP-0T were older, had higher biopsy and pathologic
      Gleason grade, and higher preoperative prostate specific antigen (all p <=
      0.023). Baseline urinary function was similar. Postoperatively, RARP-0T versus
      RARP-T was associated with higher 5-month urinary function scores (69.7 versus
      64, p = 0.049). In adjusted analyses, RARP-0T versus RARP-T was associated with
      improved 5-month urinary function [Parameter Estimate (PE) 7.37, Standard Error
      (SE) 2.67, p = 0.006], while bilateral versus non-/unilateral nerve-sparing was
      associated with improved 12-month urinary function and continence (both p <=
      0.035). RARP-0T versus RARP-T was associated with shorter operative times (PE
      6.66, SE 1.90, p = 0.001) and higher EBL (PE 20.88, SE 6.49, p = 0.001). There
      were no significant differences in PSM. CONCLUSIONS: While the use of tension
      aids in dissection of anatomic planes, avoidance of NVB counter-traction and
      minimizing tension on the rhabdosphincter during apical dissection attenuates
      neuropraxia and leads to earlier urinary function recovery. Bilateral versus non
      /unilateral nerve-sparing also improves urinary function recovery.

PMID- 23135640
TI  - Interaction of L-cysteine with naked gold nanoparticles supported on HOPG: a high
      resolution XPS investigation.
AB  - We report the results of a synchrotron-based high-resolution XPS study of the
      interaction of L-cysteine (Cys) with well-characterized colloidal gold
      nanoparticles (NPs, typical size 3-4 nm), which were pre-deposited on highly
      oriented pyrolytic graphite and then brought into contact with the aqueous
      solution of Cys by drop-casting. By comparison with data previously obtained for
      Cys deposition on flat Au substrates (single crystals and high quality films), we
      demonstrate the formation of a strong Cys/NP thiolate bond. The analysis of the
      line shape and adsorbate-induced Au 4f core level shift, backed by simulations of
      the NP structure, reveals the interaction of Cys with low-coordinated Au atoms
      belonging to the NP edge and corners. The analysis of the N 1s core-level
      indicates that neutral molecules are the most abundant species. The small facet
      size limits the formation of extended networks of zwitterionic molecules, typical
      of single crystal surfaces. This study provides a spectroscopic insight into the
      intense poisoning effect caused by a limited amount of Cys on Au catalysts
      described in previous reports.

PMID- 23135641
TI  - The new nickel tellurite chloride compound Ni15Te12O34Cl10--synthesis, crystal
      structure and magnetic properties.
AB  - A new nickel tellurite oxohalide, Ni(15)Te(12)O(34)Cl(10), has been prepared by
      chemical vapour transport reactions and the crystal structure was determined by
      single-crystal X-ray diffraction. The compound crystallizes in the triclinic
      space group P1[combining macron] with the pseudomonoclinic cell parameters a =
      10.3248(6) A, b = 10.3249(6) A, c = 11.6460(8) A, alpha = 73.782(6) degrees ,
      beta = 73.782(6) degrees , gamma = 63.51(2) degrees , Z = 1, R(1) = 0.0264. The
      Ni(2+) ions have octahedral [NiO(6)] and [NiO(4)Cl(2)] coordinations, the Te(4+)
      ions have one-sided [TeO(3)] and [TeO(4)] coordinations. The crystal structure
      can be described as consisting of nickel oxide ribbons extending along (001) that
      are connected by corner sharing [TeO(3)] and [TeO(4)] groups to build the open
      framework structure. The chlorine atoms and the Te-lone pairs are facing voids in
      the oxide framework. The new compound undergoes two successive antiferromagnetic
      ordering transitions at ~50 K and ~10 K. The Curie-Weiss temperature obtained
      from detailed evaluation of the high-temperature magnetic susceptibilities is
      positive indicating predominant ferromagnetic superexchange interactions between
      the Ni magnetic moments.

PMID- 23135642
TI  - Tribute to filler science.

PMID- 23135643
TI  - Five-year retrospective review of safety, injected volumes, and longevity of the
      hyaluronic acid Belotero Basic for facial treatments in 317 patients.
AB  - BACKGROUND: Hyaluronic acids (HA) fillers abound in the European community, many
      with different names in different countries. One such HA is Belotero Basic,
      recently approved by the FDA in the United States. OBJECTIVE: The objective of
      this article is to report on use of this HA in a German clinic, over a period of
      5+ years, in 317 patients (668 treatments). METHODS AND MATERIALS: Authors
      retrospectively examined patient charts of 317 patients (312 females), aged 24 to
      87 years. Chart review showed areas treated, range of volumes per area, and mean
      volumes. Patient satisfaction data was collected anecdotally over the five years.
      RESULTS: Volumes of the HA injected ranged from 0.2 mL to 3.0 mL, depending on
      the area being treated. No serious adverse events were noted in the chart review,
      nor was any Tyndall effect observed in the treated areas. Anecdotal information
      suggests high patient satisfaction with results, based on the return of these
      patients to the clinic for other treatments over the more than five years.
      CONCLUSION: Belotero Basic provides aesthetically pleasing results for treatment
      of facial defects, without carrying a risk of serious adverse events. North
      American physicians now have a new HA to consider as part of their treatment
      protocols.

PMID- 23135644
TI  - Histologic improvement in photodamage after 12 months of treatment with tretinoin
      emollient cream (0.02%).
AB  - BACKGROUND AND OBJECTIVE: Topical retinoids, such as tretinoin, have been
      established as the gold standard for the treatment of photodamaged skin. This was
      a single-center, open-label, single-group, observational histologic subanalysis
      of 3 of 19 patients participating in a study of the efficacy and safety of
      tretinoin emollient cream 0.02% for the treatment of moderate to severe facial
      photodamage. METHODS: Subjects were female, 18 years of age or older, and
      instructed to apply tretinoin 0.02% to the treatment areas for 12 months.
      Histology was undertaken using facial photographs and 2-mm biopsies of the
      lateral canthus area that were obtained from 3 subjects at baseline and 12
      months. RESULTS: Histopathologic analyses revealed evidence of extensive solar
      elastosis at baseline for 2 of the 3 subjects who were white, with moderate
      elastosis observed for the third subject who was African American. Histologic
      improvements in photodamage following 12 months of treatment with tretinoin 0.02%
      were observed for each subject. Improvements included smoothing of the epidermis,
      a slightly thinner keratin layer, and thin, comparatively straight elastic and
      collagen fibers in the mid- to deep-dermal layer. CONCLUSIONS: The histologic
      changes in all subjects could be attributed to a remodeling (elastin) or repair
      (collagen) process that affected the connective tissue fibers in all layers of
      the dermis. These results suggest that tretinoin 0.02% may be an effective
      treatment for photodamage, and additional evaluation is warranted in future
      studies.

PMID- 23135645
TI  - Consideration of muscle mass in glabellar line treatment with botulinum toxin
      type A.
AB  - The introduction of botulinum neurotoxin type A (BoNTA) for the treatment of
      glabellar lines marked a revolution in aesthetic medicine, allowing for
      noninvasive facial rejuvenation and sculpting. Treatment of the glabellar area
      requires a thorough understanding of facial anatomy and the interaction of
      adjacent muscle groups with respect to facial expression. Because the muscles
      underlying the glabella are among the larger muscles commonly treated with BoNTA,
      they may require higher doses than other facial sites. In addition, men typically
      have a greater glabellar muscle mass than women and require larger BoNTA doses.
      For optimal outcomes, it is necessary to account for individual variation in
      muscle mass, anatomy, and function to determine the proper dose, number, and
      location of injections. The validated Medicis Glabellar Muscle Mass Scale was
      developed to facilitate research on dose adjustment for muscle mass in the
      glabella and can be applied as a clinical tool. This review will discuss
      techniques for optimizing BoNTA treatment of the glabella, with emphasis on the
      need to assess muscle mass in individual patients and adjust BoNTA dosing and
      technique accordingly.

PMID- 23135646
TI  - The "skinny"on Sculptra: a practical primer to volumization with poly-L-lactic
      acid.
AB  - Poly-L-lactic acid (PLLA) is a biostimulatory agent that can correct bony and
      soft tissue facial deficiencies by producing gradual volume restoration. Proper
      patient selection and clear expectations are important to treatment success.
      Correct product preparation, injection technique, and patient follow-up
      correlates with increased patient safety, outcomes, and satisfaction. Alone, or
      in combination with other rejuvenative procedures, Sculptra(r) provides longer
      lasting improvement to signs of facial aging.

PMID- 23135647
TI  - Safety of dermal fillers.
AB  - Facial wrinkles are the most visible morphological change of the aging process.
      Therefore, several rejuvenation methods have been developed to cure these unloved
      signs of the times, such as botulinum toxin, laser treatments as well as topical
      active ingredients. Recently, dermal fillers have become a popular means of
      addressing contour defects and soft-tissue augmentation. Although this aesthetic
      treatment is considered to be relatively safe, the use of injectable dermal
      fillers is a minimally-invasive treatment, and as with any medical procedure,
      there is a risk for unwanted side effects.

PMID- 23135648
TI  - The basic science of dermal fillers: past and present Part I: background and
      mechanisms of action.
AB  - Dermal fillers have provided a safe and effective means for aesthetic soft tissue
      augmentation, and have experienced a dramatic increase in popularity during the
      past 10 years. Much focus has been placed upon filler technique and patient
      outcomes. However, there is a relative lack of literature reviewing the basic
      science of dermal fillers, which is vital to a physician's understanding of how
      each product behaves in vivo. Part I of this article reviews the basic science
      and evolution of both historical and contemporary dermal fillers; Part II
      examines their adverse effects. We endeavor to provide the physician with a
      practical approach to choosing products that maximize both aesthetic outcome and
      safety.

PMID- 23135649
TI  - The basic science of dermal fillers: past and present Part II: adverse effects.
AB  - The ideal dermal filler should offer long-lasting aesthetic improvement with a
      minimal side-effect profile. It should be biocompatible and stable within the
      injection site, with the risk of only transient undesirable effects from
      injection alone. However, all dermal fillers can induce serious and potentially
      long-lasting adverse effects. In Part II of this paper, we review the most common
      adverse effects related to dermal filler use.

PMID- 23135650
TI  - Cheek augmentation improves feelings of facial attractiveness.
AB  - OBJECTIVE: Aesthetic fillers aim to rejuvenate the aging face, but the true end
      goal is to help patients feel better about their appearance. Cheek augmentation
      seems to elicit immediate recognition of an improved appearance. This study aims
      to quantify that impression. METHODS: 10 women aged 40 to 60 years were not
      preselected but were the first 10 women willing to undergo the study who fit the
      inclusion and exclusion criteria. Prior to receiving the filler, participants
      were asked to rate on a visual analog scale (VAS) from 1 to 6 how they felt about
      their appearance. Each woman received 1.0 cc of hyaluronic acid filler (Perlane,
      Medicis Corporation, Phoenix, AZ) into each cheek. Two weeks later they returned
      for photos and to complete the same VAS scale. RESULTS: Seven of ten women felt
      0.5 to 2 points better about their appearance as measured by their VAS responses.
      CONCLUSION: Cheek augmentation improves how a woman feels about her
      attractiveness.

PMID- 23135651
TI  - Six steps to the "perfect" lip.
AB  - Full lips have always been associated with youth and beauty. Because of this, lip
      enhancement is one of the most frequently requested procedures in a cosmetic
      practice. For novice injectors, we recommend hyaluronic acid (HA) as the filler
      of choice. There is no skin test required; it is an easily obtainable, "off-the
      shelf" product that is natural feeling when skillfully implanted in the soft
      tissues. Hyaluronic acid is easily reversible with hyaluronidase and, therefore,
      has an excellent safety profile. While Restylane(r) is the only FDA-approved HA
      filler with a specific indication for lip augmentation, one can use the following
      HA products off-label: Juvederm(r) Ultra, Juvederm Ultra Plus, Juvederm Ultra XC,
      Juvederm Ultra PLUS XC, Restylane-L(r), Perlane(r), Perlane-L(r), and
      Belotero(r). We present our six steps to achieve aesthetically pleasing augmented
      lips. While there is no single prescription for a "perfect" lip, nor a "one size
      fits all" approach for lip augmentation, these 6 steps can be used as a basic
      template for achieving a natural look. For more comprehensive, global perioral
      rejuvenation, our 6-step technique can be combined with the injection of
      neuromodulating agents and fractional laser skin resurfacing during the same
      treatment session.

PMID- 23135652
TI  - An international perspective on fillers in dermatology-from an American
      perspective.
AB  - This manuscript is intended to give one an international perspective on the use
      of fillers around the world-what makes some of them special and what is the need
      and what is the purpose of having so many fillers in this global dermatologic
      community we live in. In the US, we have a finite number of fillers and only a
      handful more currently going through FDA testing. We demand much from our fillers
      in terms of safety and efficacy, and for all of us in the US, this is a very good
      reason to keep the numbers of fillers available to a reasonable number.

PMID- 23135653
TI  - Brighter eyes: combined upper cheek and tear trough augmentation: a systematic
      approach utilizing two complementary hyaluronic acid fillers.
AB  - Non-surgical rejuvenation of the periorbital-cheek complex can be effectively and
      safely accomplished using a combination of two hyaluronic acid (HA) fillers with
      distinct viscosities. We present a series of 21 patients with mild to moderate
      tear trough deformities who were treated with concomitant injection of two dermal
      fillers (Restylane(r) and Perlane(r)). Procedural technique entailed micro-depot
      injections of the finer viscosity HA into the sub-muscular plane along the
      orbital rim followed by manual massage. Secondly, injections of the thicker, more
      firm HA were placed in the sub-muscular and/or deep dermal spaces in the upper
      malar and lateral zygomatic areas and in the medial aspect of the temporal fossa.
      On average 0.5 mL Restylane and 0.5 mL Perlane were used per side. Statistically
      significant improvement in modified Wrinkle Severity Rating Scale scores was seen
      at 20 weeks. Overall improvement in modified Global Aesthetic Improvement Scale
      scores occurred in 20 out of 21 patients. Mean patient satisfaction scores
      increased by 2 grades relative to baseline. Patients' self-reported overall mean
      improvement was 2.23, indicating moderate (26% to 50%) to good (51% to 75%)
      improvement. Side effects were limited to transient bruising and swelling. No
      patients required dissolution of injectant with hyaluronidase. Overall, this
      combination filler procedure was found to produce both statistically significant
      and clinically apparent improvement and was associated with an extremely high
      degree of patient satisfaction.

PMID- 23135654
TI  - Filler injections with the blunt-tip microcannula.
AB  - BACKGROUND: Microcannulas with blunt tips for filler injections have recently
      been developed for use with dermal fillers. Their utility, ease of use, cosmetic
      outcomes, perceived pain, and satisfaction ratings amongst patients in terms of
      comfort and aesthetic outcomes when compared to sharp hypodermic needles has not
      previously been investigated. OBJECTIVE: To compare injections of filler with
      microcannulas versus hypodermic needles in terms of ease of use, amount of filler
      required to achieve desired aesthetic outcome, perceived pain by patient, adverse
      events such as bleeding and bruising and to demonstrate the advantages of single
      port injection technique with the blunt-tip microcannula. MATERIALS AND METHODS:
      Ninety-five patients aged 30 to 76 years with a desire to augment facial,
      decollete, and hand features were enrolled in the study. Subjects were recruited
      in a consecutive manner from patients interested in receiving dermal filler
      augmentation. Each site was cleaned with alcohol before injection. Anesthesia was
      obtained with a topical anesthesia peel off mask of lidocaine/tetracaine. Cross
      linked hyaluronic acid (20 mg to 28 mg per mL) was injected into the mid-dermis.
      The microcannula or a hypodermic needle was inserted the entire length of the
      fold, depression or lip and the filler was injected in a linear retrograde
      fashion. The volume injected was variable, depending on the depth and the extent
      of the defect. The injecting physician assessed the ease of injection. Subjects
      used the Visual Analog Scale (0-10) for pain assessment. Clinical efficacy was
      assessed by the patients and the investigators immediately after injection, and
      at one and six months after injection using the Global Aesthetic Improvement
      Scale (GAIS) and digital photography. RESULTS: Overall, the Global Aesthetic
      Improvements Scale (GAIS) results were excellent (55%), moderate (35%), and
      somewhat improved (10%) one month after the procedure, decreasing to 23%, 44%,
      and 33%, respectively, at the six month evaluation. There was no significant
      differences in the GAIS score between the microcannula and the hypodermic needle.
      However, the Visual Analog Scale for pain assessment during the injections was
      quite different. The pain was described as 3 (mild) for injections with the
      microcannula, increasing to 6 (moderate) for injections with the hypodermic
      needle. Bruising and ecchymosis was more marked following use of the hypodermic
      needle. CONCLUSION: Using the blunt-tip microcannula as an alternative to the
      hypodermic needles has simplified filler injections and produced less bruising,
      echymosis, and pain with faster recovery.

PMID- 23135655
TI  - Adjunctive use of a facial moisturizer SPF 30 containing ceramide precursor
      improves tolerability of topical tretinoin 0.05%: a randomized, investigator
      blinded, split-face study.
AB  - OBJECTIVES: To assess the benefit of adjunctive use of a SPF 30 moisturizing
      lotion in reducing local side effects associated with atopical tretinoin cream.
      METHODS: This was a randomized, investigator/evaluator-blinded, split-face
      comparison in subjects with healthy skin. Subjects applied tretinoin cream 0.05%
      once daily to the whole face and Cetaphil 174; Dermacontrol Moisturizer (CDM)
      once daily to one side of the face based on randomization. Tolerability,
      perference and skin hydration were evaluated at each week, and a cosmetic
      acceptability questionnaire regarding CDM was completed at the end of the study.
      RESULTS: The majority (about 83% to 86%) of subjects experienced skin irritations
      on both sides of their face, though predominantly mild for the CDM + tretinoin
      treated side. Tolerability preferences favored the CDM+tretinoin sides.
      Adjunctive use of CDM with a topical tretinoin cream improves tolerance of the
      treatment.

PMID- 23135656
TI  - Delay techniques for local flaps in dermatologic surgery.
AB  - Local flaps may be required to reconstruct defects on the face, neck, and scalp.
      Occasionally, delay techniques are indicated to reduce the risk for flap ischemia
      and subsequent necrosis. Delay may be employed before the flap is raised, as done
      to improve blood supply to a random flap when length to breadth proportions are
      not ideal, or after the flap is raised and before separation of the pedicle in
      the final reconstructive step to improve vascularity in the distal end of an
      interpolation flap. We present our techniques and results of delay procedures for
      interpolation and similar flaps.

PMID- 23135657
TI  - In vivo reflectance confocal microscopy features of discoid lupus erythematosus.
AB  - BACKGROUND: Discoid lupus erythematosus (DLE) is an inflammatory condition
      characterized by round demarcated lesions with varying amounts of erythema,
      telangiectasia, scaling, follicular plugging, dyspigmentation, atrophy, and
      scarring. Clinical diagnosis can be confirmed through biopsy samples; reflectance
      confocal microscopy (RCM) is also emerging as an accurate diagnostic tool.
      OBJECTIVE AND METHODS: Our objective was to examine the features of discoid lupus
      erythematosus on reflectance confocal microscopy. Two patients presenting with
      discoid lupus erythematosus were imaged using RCM. Features seen in RCM were
      correlated with those seen in histopathology. RESULTS: Reflectance confocal
      microscopy images of discoid lupus erythematosus yielded features
      characteristically seen in histopathological samples including inflammatory
      cells, inflammation at the dermo-epidermal junction, pigment incontinence, and
      vacuolar degeneration. CONCLUSION: Reflectance confocal microscopy is a useful
      tool in the diagnosis of discoid lupus erythematosus. Features described in these
      two cases as well as prior research have yielded sufficient data to allow for the
      formulation of useful RCM diagnostic algorithms. Further studies with a larger
      patient population will help in confirming and describing new features of DLE on
      RCM.

PMID- 23135659
TI  - Antiphospholipid antibody syndrome secondary to trimethoprim/sulfamethoxazole.
AB  - Antiphospholipid antibody syndrome (APS) results from autoantibodies to cell
      surface phospholipids or phospholipid-binding proteins resulting in clotting
      anomalies and can have devastating sequelae, including stroke, deep venous
      thrombosis, pulmonary embolism, and recurrent spontaneous abortions. However,
      cutaneous manifestations are the first sign of APS in up to 41% of patients. We
      present a case report of APS that developed several days after taking
      trimethoprim/sulfamethoxazole. The clinical and pathological features of this
      unique presentation, differential diagnoses, and treatments are discussed.

PMID- 23135661
TI  - A pathergic response to fractional CO2.
AB  - Pathergy is a nonspecific response to stimuli seen in a multitude of disease
      states. We present what we feel is a unique variant of this phenomenon, a case of
      multiple keratoacanthomas developing following treatment with Fractional CO2.
      This state of acute tumor emergence, which is similar to an isomorphic response,
      is believed to be related to changes in both the inflammatory and immune
      response. It is imperative that one keeps this process in their differential when
      evaluating a patient that has not only a potential predisposing disease, but also
      a history of traumatic exposure.

PMID- 23135662
TI  - Griscelli syndrome associated with hemophagocytic lymphohistiocytosis.

PMID- 23135663
TI  - Systemic antioxidants and skin health.
AB  - Most dermatologists agree that antioxidants help fight free radical damage and
      can help maintain healthy skin. They do so by affecting intracellular signaling
      pathways involved in skin damage and protecting against photodamage, as well as
      preventing wrinkles and inflammation. In today's modern world of the rising
      nutraceutical industry, many people, in addition to applying topical skin care
      products, turn to supplementation of the nutrients missing in their diets by
      taking multivitamins or isolated, man-made nutraceuticals, in what is known as
      the Inside-Out approach to skin care. However, ingestion of large quantities of
      isolated, fragmented nutrients can be harmful and is a poor representation of the
      kind of nutrition that can be obtained from whole food sources. In this
      comprehensive review, it was found that few studies on oral antioxidants
      benefiting the skin have been done using whole foods, and that the vast majority
      of current research is focused on the study of compounds in isolation. However,
      the public stands to benefit greatly if more research were to be devoted toward
      the impact that physiologic doses of antioxidants (obtained from fruits,
      vegetables, and whole grains) can have on skin health, and on health in general.

PMID- 23135664
TI  - Microdermabrasion: molecular mechanisms unraveled, part 2.
AB  - Microdermabrasion (MDA) remains a common in-office procedure for many
      dermatologic practices. The procedure offers minimal downtime with a low
      incidence of side effects, making it a relatively desirable option for skin
      rejuvenation. Investigators have identified many of the molecular mechanisms
      behind this technology in an attempt to optimize clinical results. In particular,
      activation of the wound healing response plays a key role in the remodeling of
      post-MDA treated skin, although this response varies based on the type of MDA
      employed. In addition, advances in MDA technology offer new and promising ways to
      enhance transcutaneous penetration of active ingredients to improve clinical
      outcomes. Our review addresses innovative applications of MDA in the last 10
      years of research.

PMID- 23135665
TI  - Is white coat hypertension a concern in Mohs micrographic surgery?
AB  - OBJECTIVE: To examine white coat hypertension (WCHTN) in patients presenting for
      Mohs micrographic surgery (MMS) to determine whether it should be a concern.
      METHODS: In this prospective study, blood pressure (BP) was recorded in 100
      consecutive patients who presented for MMS consultation and a subsequent MMS
      procedure, and compared on both days. Statistical analysis was performed using
      the paired Student t test and the significance of the findings was determined
      based on the corresponding P values. Progression from normotensive to
      hypertensive state while the doctor was in the room was stratified based on the
      patient's age, gender, and histories of smoking, hypertension (HTN), diabetes,
      and hyperlipidemia; as well as whether the doctor was wearing a white lab coat
      over blue surgical scrubs (50 patients) or blue surgical scrubs alone (50
      patients). RESULTS: BP increased from baseline when the doctor entered the room
      and then decreased towards baseline after five minutes of the doctor being
      present. Elevation in BP was more evident in younger people, males, and those
      with HTN and hyperlipidemia. BP was slightly higher on the day of the
      consultation than on the day of the procedure. A higher number of patients became
      hypertensive when the doctor wore a white lab coat over blue surgical scrubs vs
      blue surgical scrubs alone. However, these changes in BP did not prove to be
      statistically significant. CONCLUSION: Brief periods of WCHTN were seen on both
      days. However, these elevations in BP were not statistically significant and
      decreased towards baseline after five minutes. There were no cases in which
      elevation in BP associated with WCHTN was sufficient to result in the need to
      postpone or cancel MMS.

PMID- 23135666
TI  - Microdermabrasion: molecular mechanisms unraveled, part 1.
AB  - Microdermabrasion (MDA) remains a common in-office procedure for many
      dermatologic practices.The procedure offers minimal downtime with a low incidence
      of side effects, making it a relatively desirable option for skin rejuvenation.
      Investigators have identified many of the molecular mechanisms behind this
      technology in an attempt to optimize clinical results. In particular, activation
      of the wound healing response plays a key role in the remodeling of post-MDA
      treated skin, although this response varies based on the type of MDA
      employed.While many studies discuss the clinical applications of MDA and their
      relation to histologic changes found after treatment, few address the basic
      science behind the technology.Our review covers progress made in the last 10
      years of research, with an emphasis on the molecular mechanisms.

PMID- 23135667
TI  - Effects of oral isotretinoin on serum folic acid levels.
AB  - OBJECTIVE: Acne vulgaris is one of the most common skin disorders, and oral
      isotretinoin has widely been used as a treatment for severe and resistant cases
      in recent years. This article considers the controversy over systemic
      isotretinoin's effect on the serum level of folic acid and its implications for
      health. METHODS: This study was conducted to assess the effect of systemic
      isotretinoin on the serum level of folic acid. Sixty-one patients, including 38
      women and 23 men (mean age 23.6 6 years) with severe or moderate acne that was
      resistant to conventional treatments, were supplemented with 0.5 mg/kg/d of oral
      isotretinoin for 30 days. They were instructed not to use any other drugs having
      an effect on the folic acid level nor change their diet. The serum levels of
      folic acid were measured at the baseline and at the end of the treatment period.
      Statistical analyses were carried out using the paired t test. RESULTS: Mean
      levels of folic acid were 26.75 9.42 nmol/L at baseline, and and 23.6 8.42 nmol/L
      after 30 days of isotretinoin supplementation. This showed a significant decrease
      in the serum level of folic acid (P=.008). CONCLUSION: Given the significant
      decrease in the serum level of folic acid following a 30-day use of oral
      isotretinoin in acne patients, and considering the important role of folic acid
      in metabolic functions, we recommend further studies to assess the effect of
      longer periods of isotretinoin treatment, in addition to studies including other
      relevant factors in folic acid metabolism (e.g., serum homocysteine levels).
      Moreover, folic acid supplementation in acne patients using isotretinoin is
      recommended.

PMID- 23135668
TI  - Topical pimecrolimus 1% reverses long-term suberythemal ultraviolet B-induced
      epidermal Langerhans cell reduction and morphologic changes in mice.
AB  - OBJECTIVE: Some literature reported that topical calcineurin inhibitors (TCIs)
      did not accelerate photocarcinogenesis in hairless mice after long-term simulated
      solar radiation. In this work, we investigate the effects of topical pimecrolimus
      1% on long-term suberythemal ultraviolet B (UVB) irradiated epidermal Langerhans
      cells (LCs) in mice. METHODS: Thirty female mice were randomly divided into two
      groups, including four subgroups: (1A) control, (1B) pimecrolimus 1% only, (2A)
      25 mJ/cm2 UVB only, (2B) UVB plus pimecrolimus. After being treated for 60 days,
      the dorsal skin was collected and given immunohistochemical staining of active
      caspase 3, and immunofluorescence staining for cluster of differentiation 1a
      (CD1a). RESULTS: Our results show that, compared with the control subgroup, the
      CD1a+ LC number in the epidermal sheet of the UVB-only subgroup decreased
      substantially from 578.6 per mm2 to 227 per mm2 (P<.001). Compared with the UVB
      only subgroup, the UVB plus pimecrolimus subgroup significantly restored the LC
      number from 227 per mm2 to 475.7 per mm2 (P<.001). Compared with other subgroups,
      the LC morphology of the UVB-only subgroup became rounder, and the LC dendrites
      became shorter. There were no significant active caspase 3-positive cells in the
      epidermis in any of the four subgroups. CONCLUSION: Our results show that topical
      pimecrolimus 1% reverses long-term UVB-induced epidermal LC reduction and
      morphologic changes in mice, where the exact mechanism is likely not related to
      apoptosis.

PMID- 23135670
TI  - First description of a musculoskeletal linkage in an adipose fin: innovations for
      active control in a primitively passive appendage.
AB  - Adipose fins are enigmatic appendages found between the dorsal and caudal fins of
      some teleostean fishes. Long thought to be vestigial, degenerate second dorsal
      fins, remnants of the primitive gnathostome condition, adipose fins have since
      been recognized as novel morphologies. Unique among the fins of extant fishes,
      adipose fins have uniformly been described as passive structures, with no
      associated musculature. Here we provide the first description of a
      musculoskeletal linkage in an adipose fin, identified in the sun catfish
      Horabagrus brachysoma. Modified supracarinalis posterior muscles insert from the
      dorsal midline anterior to the adipose fin by tendons onto the fin base. An
      additional pair of posterior adipose-fin muscles also inserts upon the fin base
      and lay posterolateral to the fin, superficial to the axial muscle. This
      musculoskeletal linkage is an evolutionary innovation, a novel mechanism for
      controlling adipose-fin movement. These muscles appear to exemplify two
      approaches by which fins evolve to be actively controlled. We hypothesize that
      the anterior muscles arose through co-option of an existing fin linkage, while
      the posterior muscles originated as de novo fin muscles. These findings present
      adipose fins as a rich system within which to explore the evolution of novel
      vertebrate appendages.

PMID- 23135671
TI  - The case for a dorsomedial area in the primate 'third-tier' visual cortex.

PMID- 23135672
TI  - Palaeoecological evidence of a historical collapse of corals at Pelorus Island,
      inshore Great Barrier Reef, following European settlement.
AB  - The inshore reefs of the Great Barrier Reef (GBR) have undergone significant
      declines in water quality following European settlement (approx. 1870 AD).
      However, direct evidence of impacts on coral assemblages is limited by a lack of
      historical baselines prior to the onset of modern monitoring programmes in the
      early 1980s. Through palaeoecological reconstructions, we report a previously
      undocumented historical collapse of Acropora assemblages at Pelorus Island
      (central GBR). High-precision U-series dating of dead Acropora fragments
      indicates that this collapse occurred between 1920 and 1955, with few dates
      obtained after 1980. Prior to this event, our results indicate remarkable long
      term stability in coral community structure over centennial scales. We suggest
      that chronic increases in sediment flux and nutrient loading following European
      settlement acted as the ultimate cause for the lack of recovery of Acropora
      assemblages following a series of acute disturbance events (SST anomalies,
      cyclones and flood events). Evidence for major degradation in reef condition
      owing to human impacts prior to modern ecological surveys indicates that current
      monitoring of inshore reefs on the GBR may be predicated on a significantly
      shifted baseline.

PMID- 23135673
TI  - Resource partitioning among top predators in a Miocene food web.
AB  - The exceptional fossil sites of Cerro de los Batallones (Madrid Basin, Spain)
      contain abundant remains of Late Miocene mammals. From these fossil assemblages,
      we have inferred diet, resource partitioning and habitat of three sympatric
      carnivorous mammals based on stable isotopes. The carnivorans include three apex
      predators: two sabre-toothed cats (Felidae) and a bear dog (Amphicyonidae).
      Herbivore and carnivore carbon isotope (delta(13)C) values from tooth enamel
      imply the presence of a woodland ecosystem dominated by C(3) plants. delta(13)C
      values and mixing-model analyses suggest that the two sabre-toothed cats, one the
      size of a leopard and the other the size of a tiger, consumed herbivores with
      similar delta(13)C values from a more wooded portion of the ecosystem. The two
      sabre-toothed cats probably hunted prey of different body sizes, and the smaller
      species could have used tree cover to avoid encounters with the larger felid. For
      the bear dog, delta(13)C values are higher and differ significantly from those of
      the sabre-toothed cats, suggesting a diet that includes prey from more open
      woodland. Coexistence of the sabre-toothed cats and the bear dog was likely
      facilitated by prey capture in different portions of the habitat. This study
      demonstrates the utility of stable isotope analysis for investigating the
      behaviour and ecology of members of past carnivoran guilds.

PMID- 23135674
TI  - Viral mutation rates: modelling the roles of within-host viral dynamics and the
      trade-off between replication fidelity and speed.
AB  - Many viruses, particularly RNA viruses, mutate at a very high rate per genome per
      replication. One possible explanation is that high mutation rates are selected to
      meet the challenge of fluctuating environments, including the host immune
      response. Alternatively, recent studies argue that viruses evolve under a trade
      off between replication speed and fidelity such that fast replication is
      selected, and, along with it, high mutation rates. Here, in addition to these
      factors, we consider the role of viral life-history properties: namely, the
      within-host dynamics of viruses resulting from their interaction with the host.
      We develop mathematical models incorporating factors occurring within and between
      hosts, including deleterious and advantageous mutations, host death owing to
      virulence and clearance of viruses by the host. Beneficial mutations confer both
      a within-host and a transmission advantage. First, we find that advantageous
      mutations have only a weak effect on the optimal genomic mutation rate. Second,
      viral life-history properties have a large effect on the mutation rate. Third,
      when the speed-fidelity trade-off is included, there can be two locally optimal
      mutation rates. Our analysis provides a way to consider how life-history
      properties combine with biochemical trade-offs to shape mutation rates.

PMID- 23135675
TI  - Regulation of hard alpha-keratin mechanics via control of intermediate filament
      hydration: matrix squeeze revisited.
AB  - Mammalian hard alpha-keratins are fibre-reinforced biomaterials that consist of
      10 nm intermediate filaments (IFs) embedded in an elastomeric protein matrix.
      Recent work suggests that the mechanical properties of IFs are highly sensitive
      to hydration, whereas hard alpha-keratins such as wool, hair and nail are
      relatively hydration insensitive. This raises the question of how mammalian
      keratins remain stiff in water. The matrix squeeze hypothesis states that the IFs
      in hard alpha-keratins are stiffened during an air-drying step during
      keratinization, and subsequently locked into a dehydrated state via the oxidation
      and cross-linking of the keratin matrix around them. The result is that even when
      hard alpha-keratins are immersed in water, their constituent IFs remain
      essentially 'dry' and therefore stiff. This hypothesis makes several predictions
      about the effects of matrix abundance and function on hard alpha-keratin
      mechanics and swelling behaviour. Specifically, it predicts that high matrix
      keratins in water will swell less, and have a higher tensile modulus, a higher
      yield stress and a lower dry-to-wet modulus ratio. It also predicts that
      disruption of the keratin matrix in water should lead to additional swelling, and
      a drop in modulus and yield stress. Our results are consistent with these
      predictions and suggest that the keratin matrix plays a critical role in
      governing the mechanical properties of mammalian keratins via control of IF
      hydration.

PMID- 23135676
TI  - Integrative modelling of animal movement: incorporating in situ habitat and
      behavioural information for a migratory marine predator.
AB  - A fundamental goal in animal ecology is to quantify how environmental (and other)
      factors influence individual movement, as this is key to understanding
      responsiveness of populations to future change. However, quantitative
      interpretation of individual-based telemetry data is hampered by the complexity
      of, and error within, these multi-dimensional data. Here, we present an
      integrative hierarchical Bayesian state-space modelling approach where, for the
      first time, the mechanistic process model for the movement state of animals
      directly incorporates both environmental and other behavioural information, and
      observation and process model parameters are estimated within a single model.
      When applied to a migratory marine predator, the southern elephant seal (Mirounga
      leonina), we find the switch from directed to resident movement state was
      associated with colder water temperatures, relatively short dive bottom time and
      rapid descent rates. The approach presented here can have widespread utility for
      quantifying movement-behaviour (diving or other)-environment relationships across
      species and systems.

PMID- 23135677
TI  - Not just passengers: pigeons, Columba livia, can learn homing routes while flying
      with a more experienced conspecific.
AB  - For animals that travel in groups, the directional choices of conspecifics are
      potentially a rich source of information for spatial learning. In this study, we
      investigate how the opportunity to follow a locally experienced demonstrator
      affects route learning by pigeons over repeated homing flights. This test of
      social influences on navigation takes advantage of the individually distinctive
      routes that pigeons establish when trained alone. We found that pigeons learn
      routes just as effectively while flying with a partner as control pigeons do
      while flying alone. However, rather than learning the exact route of the
      demonstrator, the paired routes shifted over repeated flights, which suggests
      that the birds with less local experience also took an active role in the
      navigational task. The efficiency of the original routes was a key factor in how
      far they shifted, with less efficient routes undergoing the greatest changes. In
      this context, inefficient routes are unlikely to be maintained through repeated
      rounds of social transmission, and instead more efficient routes are achieved
      because of the interaction between social learning and information pooling.

PMID- 23135678
TI  - Inferring the inter-host transmission of influenza A virus using patterns of
      intra-host genetic variation.
AB  - Influenza A viruses (IAVs) cause acute, highly transmissible infections in a wide
      range of animal species. Understanding how these viruses are transmitted within
      and between susceptible host populations is critical to the development of
      effective control strategies. While viral gene sequences have been used to make
      inferences about IAV transmission dynamics at the epidemiological scale, their
      utility in accurately determining patterns of inter-host transmission in the
      short-term--i.e. who infected whom--has not been strongly established. Herein, we
      use intra-host sequence data from the viral HA1 (hemagglutinin) gene domain from
      two transmission studies employing different IAV subtypes in their natural hosts-
      H3N8 in horses and H1N1 in pigs-to determine how well these data recapitulate the
      known pattern of inter-host transmission. Although no mutations were fixed over
      the course of either experimental transmission chain, we show that some minor,
      transient alleles can provide evidence of host-to-host transmission and,
      importantly, can be distinguished from those that cannot.

PMID- 23135679
TI  - Evolution of a contagious cancer: epigenetic variation in Devil Facial Tumour
      Disease.
AB  - The emergence of Devil Facial Tumour Disease (DFTD), a highly contagious cancer,
      is driving Tasmanian devils (Sarcophilus harrisii) to extinction. The cancer is a
      genetically and chromosomally stable clonal cell line which is transmitted by
      biting during social interactions. In the present study, we explore the Devil
      Facial Tumour (DFT) epigenome and the genes involved in DNA methylation
      homeostasis. We show that tumour cells have similar levels of methylation to
      peripheral nerves, the tissue from which DFTD originated. We did not observe any
      strain or region-specific epimutations. However, we revealed a significant
      increase in hypomethylation in DFT samples over time (p < 0.0001). We propose
      that loss of methylation is not because of a maintenance deficiency, as an
      upregulation of DNA methyltransferase 1 gene was observed in tumours compared
      with nerves (p < 0.005). Instead, we believe that loss of methylation is owing to
      active demethylation, supported by the temporal increase in MBD2 and MBD4 (p <
      0.001). The implications of these changes on disease phenotypes need to be
      explored. Our work shows that DFTD should not be treated as a static entity, but
      rather as an evolving parasite with epigenetic plasticity. Understanding the role
      of epimutations in the evolution of this parasitic cancer will provide unique
      insights into the role of epigenetic plasticity in cancer evolution and
      progression in traditional cancers that arise and die with their hosts.

PMID- 23135680
TI  - Impact of parasites on salmon recruitment in the Northeast Atlantic Ocean.
AB  - Parasites may have large effects on host population dynamics, marine fisheries
      and conservation, but a clear elucidation of their impact is limited by a lack of
      ecosystem-scale experimental data. We conducted a meta-analysis of replicated
      manipulative field experiments concerning the influence of parasitism by
      crustaceans on the marine survival of Atlantic salmon (Salmo salar L.). The data
      include 24 trials in which tagged smolts (totalling 283 347 fish; 1996-2008) were
      released as paired control and parasiticide-treated groups into 10 areas of
      Ireland and Norway. All experimental fish were infection-free when released into
      freshwater, and a proportion of each group was recovered as adult recruits
      returning to coastal waters 1 or more years later. Treatment had a significant
      positive effect on survival to recruitment, with an overall effect size (odds
      ratio) of 1.29 that corresponds to an estimated loss of 39 per cent (95% CI: 18
      55%) of adult salmon recruitment. The parasitic crustaceans were probably
      acquired during early marine migration in areas that host large aquaculture
      populations of domesticated salmon, which elevate local abundances of
      ectoparasitic copepods-particularly Lepeophtheirus salmonis. These results
      provide experimental evidence from a large marine ecosystem that parasites can
      have large impacts on fish recruitment, fisheries and conservation.

PMID- 23135681
TI  - Between cheap and costly signals: the evolution of partially honest
      communication.
AB  - Costly signalling theory has become a common explanation for honest communication
      when interests conflict. In this paper, we provide an alternative explanation for
      partially honest communication that does not require significant signal costs. We
      show that this alternative is at least as plausible as traditional costly
      signalling, and we suggest a number of experiments that might be used to
      distinguish the two theories.

PMID- 23135682
TI  - The evolution of fairness: explaining variation in bargaining behaviour.
AB  - Conceptions of fairness vary across the world. Identifying the drivers of this
      variation is key to understanding the selection pressures and mechanisms that
      lead to the evolution of fairness in humans. Individuals' varying fairness
      preferences are widely assumed to represent cultural norms. However, this
      assumption has not previously been tested. Fairness norms are defined as
      culturally transmitted equilibria at which bargainers have coordinated
      expectations from each other. Hence, if fairness norms exist at the level of the
      ethno-linguistic group, we should observe two patterns. First, cultural
      conformism should maintain behavioural homogeneity within an ethno-linguistic
      group. Second, bargainers' expectations should be coordinated such that proposals
      and responses to proposals should covary. Here we show that neither of these
      patterns is observed across 21 populations of the same ethno-linguistic group,
      the Pahari Korwa of central India. Our findings suggest that what constitutes a
      fair division of resources can vary on smaller scales than that of the ethno
      linguistic group. Individuals' local environments may play a central role in
      determining conceptions of fairness.

PMID- 23135683
TI  - Vaspin gene in rat adipose tissue: relation to obesity-induced insulin
      resistance.
AB  - Visceral adipose fat has been claimed to be the link between obesity and insulin
      resistance through the released adipokines. This study aimed to assess the
      expression of vaspin as one of the recent adipokines in rats abdominal
      subcutaneous and visceral fat in diet-induced obese (DIO) and in DIO performing 3
      weeks swimming exercise (DIO + EXE) compared to control and control + exercise (C
      + EXE) groups. Vaspin mRNA and protein expression assessed using RT-PCR and
      Western blotting analysis revealed vaspin expression in DIO and DIO + EXE but not
      in controls groups. In DIO group, visceral vaspin expression was higher than in
      that of subcutaneous fat and was positively correlated with body weight.
      Upregulation of visceral vaspin expression in DIO was concomitant with the
      development of insulin resistance (increase in fasting serum insulin and HOMA-IR)
      and rise in serum leptin level. Unchanged visceral vaspin mRNA in DIO + EXE rats,
      with significant improvements of insulin resistance parameters and serum leptin
      compared to DIO group was found. In conclusion, increased visceral vaspin
      expression in obesity was associated with insulin resistance. Further
      investigations into the molecular links between vaspin and obesity may unravel
      innovative therapeutic strategies in people affected by obesity-linked insulin
      resistance, metabolic syndrome, and type 2 diabetes.

PMID- 23135685
TI  - Hematopoietic stem cell transplantation: a review and recommendations for follow
      up care for the general practitioner.
AB  - The first hematopoietic stem cell transplantation (HSCT), the replacement of the
      hematopoietic system, by hematopoietic stem cells from the patient (autologous
      HSCT) or from another person (allogeneic HSCT), was performed almost 45 years
      ago. Today autologous HSCT is used to bridge hematopoietic failure after high
      dose chemotherapy for the treatment of selected hematopoietic and non
      hematopoietic tumours. Allogeneic HSCT is used to treat congenital or acquired
      marrow failure, and, more commonly, to exploit the graft versus tumour effect of
      allogeneic cells against high risk hematologic malignancies. In 2010, 30,000
      patients were treated with HSCT (12,000 allogeneic and 18,000 autologous HSCT) in
      Europe. Substantial progress has been made in the field of allogeneic HSCT in the
      last decade. First the article describes advances in patient and donor selection,
      the current concepts of choosing the optimal stem cell source and the most
      appropriate preparative regimen. Furthermore, recent advances in supportive care
      are described. We describe how these innovations have allowed indications for
      allogeneic HSCT to be expanded. Finally, prospects for future developments will
      be outlined.

PMID- 23135684
TI  - Androgen deprivation by flutamide modulates uPAR, MMP-9 expressions, lipid
      profile, and oxidative stress: amelioration by daidzein.
AB  - The growth and development of prostate gland is governed by testosterone.
      Testosterone helps in maintaining the adipose tissue stores of the body. It is
      well documented that with advancing age there has been a gradual decline in
      testosterone levels. Our aim was to study the protective role of daidzein on
      flutamide-induced androgen deprivation on matrix degrading genes, lipid profile
      and oxidative stress in Wistar rats. Sub-chronic (60 days) flutamide (30 mg/kg
      b.wt) administration resulted in marked increase in expressions of matrix
      degrading genes [matrix metalloproteases 9 and urokinase plasminogen activation
      receptor]. Additionally, it increased the levels of low density lipoproteins,
      total cholesterol, triglycerides, and lowered the levels of high density
      lipoproteins and endogenous antioxidant levels. Oral administration of daidzein
      (20 and 60 mg/kg b.wt) restituted the levels to normal. Daidzein administration
      resulted in amelioration of the prostate atrophy, degeneracy and invasiveness
      induced by flutamide. Our findings suggest that the daidzein may be given as
      dietary supplement to patients who are on androgen deprivation therapy, to
      minimize the adverse effects related to it and also retarding susceptibility of
      patients to cardiovascular diseases.

PMID- 23135686
TI  - Spontaneous intramural small-bowel hematoma secondary to anticoagulant therapy: a
      case series.
AB  - Spontaneous small-bowel hematomas most commonly involve the jejunum, followed by
      the ileum and duodenum, and occur in patients who receive excessive
      anticoagulation with phenprocoumon/warfarin or who have additional risk factors
      for bleeding. We report three cases of intramural small-bowel hematoma, all
      complications of treatment with phenprocoumon, which nowadays is used extensively
      for therapeutic and prophylactic purposes. Diagnosis can be readily attained by
      sonography and confirmed using computed tomography. Early diagnosis is crucial
      because most patients can be treated successfully without surgery. Based on this
      experience and data from the literature, conservative treatment is recommended
      for intramural intestinal hematomas, when other complications needing laparotomy
      have been excluded.

PMID- 23135688
TI  - Expected and observed mortality in critically ill patients receiving initial
      antibiotic therapy.
AB  - OBJECTIVE: To evaluate the predictors of mortality in critically ill patients
      receiving initial antibiotic therapy (IAT; < 48 h after admission). METHODS: Six
      hundred thirty-one consecutive patients admitted to an intermediate care (IMC)
      unit were included. IAT was initiated in 227 patients. Laboratory markers,
      interventions, medications, systemic inflammatory response syndrome (SIRS) and
      sepsis criteria, length of stay, and hospital mortality as well as expected
      mortality, based on the SAPSII-expanded score, were assessed retrospectively.
      Failure of IAT was defined as a rise in C-reactive protein (CRP) or leukocyte
      count on day 3 compared with the values on admission. RESULTS: Patients with IAT
      were significantly older (67 +/- 14 vs. 64 +/- 14 years; p = 0.006) and had a
      higher prevalence of chronic renal failure (33 vs. 23 %; p = 0.015), chronic
      obstructive pulmonary disease (COPD; 27 vs. 16 %; p = 0.002), malignoma (17 vs. 9
      %; p = 0.007), acute renal failure (11 vs. 4 %; p = 0.001), respiratory failure
      (22 vs. 7 %; p < 0.001), and a shock index < 1.0 (21 vs. 8 %; p < 0.001).
      Although patients with IAT did not have significantly different expected
      mortality compared with patients without IAT (19.2 vs. 14.5 %; p = 0.144), they
      did have a significantly higher observed mortality (16.7 vs. 3.7 %; p < 0.0001).
      Based on the number of SIRS criteria (0, 1, 2, or 3-4) or sepsis criteria (no
      sepsis, sepsis, or severe sepsis) fulfilled, expected mortality (16.4, 18.2,
      20.6, or 21.0 %, respectively; p = 0.955/17.5, 18.3, or 23.4 %, respectively; p =
      0.689) did not differ in IAT patients. In contrast, observed mortality differed
      significantly (4.8, 10.6, 20.6, or 29.4 %, respectively; p = 0.029/8.3, 19.7, or
      29.3 %, respectively; p = 0.013). Patients who responded to IAT did not differ
      regarding comorbidities, SIRS or sepsis criteria, but they had a lower observed
      mortality (11.9 vs. 26.3 %; p = 0.008) than patients who failed to respond to
      IAT. Central venous lines were more frequently present in patients with failure
      to IAT when compared with those with response (51 vs. 22 %; p = 0.009). In the
      subgroup of patients with acute myocardial infarction (AMI), those with IAT (n =
      41) were treated less frequently according to the current cardiac guidelines than
      those without (n = 124) CONCLUSIONS: Patients with IAT have a high morbidity
      burden and higher observed than expected mortality. The SAPSII-expanded score
      does not seem to precisely estimate the risk of in-hospital mortality in these
      patients. Failure of response to IAT was associated with an even higher
      mortality. Whether central venous lines and nonadherence to cardiac care
      guidelines influence the mortality of patients with IAT should be investigated in
      further studies.

PMID- 23135689
TI  - Lung imaging in patients with acute respiratory distress syndrome: from an
      understanding of pathophysiology to bedside monitoring.
AB  - Over the last 25 years, lung imaging has changed our understanding of acute
      respiratory distress syndrome. Alveolar recruitment, hyperinflation, and positive
      end-expiratory pressure-induced changes in lung aeration have become evaluable
      using CT, PET, and ultrasonography. The data have revealed that patients differ,
      in that the required ventilator settings vary in those with the same syndrome. At
      the bedside, however, care physicians remain blinded. Bedside tools allowing
      monitoring of mechanical ventilation, and testing of ventilator settings, are
      urgently required. The aim of the present review is to consider how lung imaging
      has facilitated the evolution of knowledge of this syndrome, and to place such
      knowledge in a clinical perspective.

PMID- 23135690
TI  - Effects of different tidal volumes for one-lung ventilation on oxygenation with
      open chest condition and surgical manipulation: a randomised cross-over trial.
AB  - BACKGROUND: The ideal tidal volume (TV) during one-lung ventilation (OLV) remains
      controversial. High TVs may increase the incidence of postoperative lung injury
      after thoracic surgery. There is nonetheless little evidence that the use of low
      TV during OLV will fail to provide adequate arterial oxygenation. We evaluated
      the influence of low (5 mL/kg-1) and high (10 mL/kg-1) TV on arterial oxygenation
      during one-lung ventilation in clinical conditions. METHODS: A hundred patients
      scheduled for lung surgery were studied. Patients were randomly assigned to
      either 30 minutes of one-lung ventilation with a TV of 10 mL/kg-1 at a rate of 10
      breaths/minute (Group 10, N.=50) or a TV of 5 mL/kg-1 with 5 cmH2O PEEP at a rate
      of 20 breaths/minute (Group 5, N.=50). According to the rules of crossover design
      during the subsequent 30 minutes, each patient received the alternative
      management. Arterial blood partial pressures, hemodynamic responses, and
      ventilatory parameters were recorded. Results are presented as means +/- SDs;
      P<0.05 was considered statistically significant. RESULTS: PaO2 was unaffected by
      TV (10 mL/kg-1: 218+/-106 versus 5 mL/kg-1: 211+/-119 mmHg, P=0.29). Calculated
      intrapulmonary shunt fraction was also similar with each TV during OLV (5 mL/kg
      1: 25+/-9% versus 10 mL/kg-1: 24+/-8%, p=0.14). In contrast, low TV significantly
      increased PaCO2 (10 mL/kg-1: 39+/-6 versus 5 mL/kg-1: 44+/-8 mmHg, P<0.001).
      There were significant differences both in peak (10 mL/kg-1: 27+/-6 versus 5
      mL/kg-1: 21+/-5 cmH2O, P<0.001) and plateau airway pressure values (10 mL/kg-1:
      22+/-6 versus 5 mL/kg-1: 18+/-5 cmH2O, P<0.001) during OLV. CONCLUSION: Low TV (5
      mL/kg-1) accompanied by 5 cmH2O PEEP provides comparable arterial oxygenation and
      intrapulmonary shunt fraction during one-lung ventilation as higher TV (10 mL/kg
      1) without PEEP.

PMID- 23135691
TI  - Rituximab in critically ill patients.
AB  - Rituximab is a monoclonal chimeric antibody used in the treatment of CD20
      positive B-cell malignancies and rheumatoid arthritis. However, it is used in
      several other off-label indications including acute graft-versus-host disease. We
      sought to critically examine the role of rituximab in the treatment of acute
      graft versus host disease (aGVHD) in critically ill patients and the potential
      associations with infectious complications in transplant recipients.

PMID- 23135692
TI  - Maternal hypotension during spinal anesthesia for caesarean delivery.
AB  - The aim of the study was to review maternal hypotension during caesarean delivery
      with spinal anesthesia. Obstetric complications, such as obstetric hemorrhage and
      problems related to concomitant maternal diseases are not considered. Reports of
      hypotension during spinal anesthesia for elective caesarean delivery are frequent
      (70-80%) when pharmacological prophylaxis is not used. Although some physical
      methods (leg wrapping, thromboembolic stockings) and the prevention of aorto
      caval compression (left lateral tilt of the uterus) are useful, main prevention
      relies on two pharmacological methods, vasopressor therapy and intravascular
      fluid loading generally in combination. Ephedrine has been the vasopressor of
      choice in obstetrics for decades but phenylephrine is now the preferred first
      line approach during elective procedures at least. Crystalloid preloading is
      clinically ineffective and should be abandoned. Crystalloid coloading at the
      onset of sympathetic blockade is better but its efficacy may depend on the volume
      infused and the speed of administration. Preloading with hydroxyethylstarch is
      more consistently effective in reducing the incidence and severity of hypotension
      and hydroxyethylstarch coloading appears equally effective. Preoperative tests
      and new monitoring devices are available to predict or permit early detection of
      hypotension, but their feasibility and reliability in routine clinical practice
      is not yet established. With these tools, it may become possible to tailor
      prophylaxis to the assessed risk of the individual. Combining a prophylactic
      vasopressor regimen with hydroxyethylstarch preloading, hydroxyethylstarch
      coloading or crystalloid coloading is the best method to decrease the incidence
      and severity of hypotension during spinal anesthesia for caesarean delivery.

PMID- 23135693
TI  - Antiemetic effects of combined methylprednisolone and tropisetron in mastectomy.
AB  - BACKGROUND: Combined dexamethasone and tropisetron have been reported more
      effective than a single drug therapy in preventing postoperative nausea and
      vomiting (PONV). However, the safety use of dexamethasone has been questioned
      recently because of the risk of secondary adrenal deficiency. Therefore, we
      hypothesized that combined tropisetron and methylprednisolone, a short-lasting
      corticoid, might provide effective prophylaxis of PONV with less effect on
      endogenous cortisol level. METHODS: In this study, 224 women undergoing modified
      radical mastectomy under general anesthesia were randomly divided into three
      groups: 1) receiving 10 mg tropisetron alone (T, N.=76); 2) 10 mg tropisetron and
      8 mg dexamethasone (TD, N.=73); or 3) 10 mg tropisetron and 40 mg
      methylprednisolone (TM, N.=75) intravenously. Serum cortisol level, episodes of
      PONV and the need for rescue antiemetic medication were recorded during first 3
      days after surgery. RESULTS: Serum cortisol significantly decreased in group TD
      (5.42+/-1.87 MUg/dL), compared with group TM (14.38+/-2.01 MUg/dL, P<0.01) and
      group T (19.52+/-1.53 MUg/dL, P<0.001) in the first day postoperatively. In the
      first 24 hours, the incidence of vomiting was significantly higher in group T
      (15.8%), compared with group TD (5.5%, P<0.05) and group TM (5.3%, P<0.05),
      respectively. The overall request for a rescue antiemetic of group T was
      significantly higher, compared with group TD and group TM (P<0.05). CONCLUSION:
      Methylprednisolone-tropisetron combination is more effective than tropisetron
      alone, and as equally effective as dexamethasone-tropisetron combination for
      preventing acute PONV in mastectomy.

PMID- 23135694
TI  - How to assess positive end-expiratory pressure-induced alveolar recruitment?
AB  - Randomized trials fail to demonstrate a decrease in mortality when high Positive
      End-Expiratory Pressure (PEEP) is applied to patients with acute respiratory
      distress syndrome. Use of PEEP in all patients without taking into consideration
      specific lung morphology, potential for recruitment and risk of lung
      hyperinflation could be one of explanations. Assessment of alveolar recruitment
      in each individual patient appears to reach a good compromise between
      optimization of mechanical ventilation and reduction of lung injury due to
      systematic application of high PEEP. The purpose of the review was to discuss
      different methods to measure alveolar recruitment aimed at selecting optimal
      PEEP. The revision of the literature includes relevant human and animal studies
      published in the past ten years describing validated and promising methods.
      Computed tomography remains the reference method to assess regional PEEP-induced
      alveolar recruitment and hyperinflation. Lung ultrasound and pressure-volume (P
      V) curve method are simple and repeatable at the bedside, but they can't provide
      information on lung hyperinflation. Electrical impedance tomography allows
      bedside assessment of tidal recruitment in dependent and nondependent regions. By
      measuring functional residual capacity, alveolar recruitment and strain can be
      estimated. Decremental PEEP titration preceded by recruitment maneuver has been
      suggested to define optimal PEEP that sustains oxygenation benefit of recruitment
      maneuver. Different methods are available to assess PEEP-induced alveolar
      recruitment. Lung ultrasound and P-V curve method can be easily used at bedside
      to assess lung recruitability and test optimal PEEP. Further development is
      required for bedside assessment combing alveolar recruitment with hyperinflation.

PMID- 23135695
TI  - Genomic analysis of Saccharomyces cerevisiae isolates that grow optimally with
      glucose as the sole carbon source.
AB  - A population of Saccharomyces cerevisiae was cultured for approximately 450
      generations in the presence of high glucose to select for genetic variants that
      grew optimally under these conditions. Using the parental strain BY4741 as the
      starting population, an evolved culture was obtained after aerobic growth in a
      high glucose medium for approximately 450 generations. After the evolution
      period, three single colony isolates were selected for analysis. Next-generation
      Ion Torrent sequencing was used to evaluate genetic changes. Greater than 100
      deletion/insertion changes were found with approximately half of these effecting
      genes. Additionally, over 180 SNPs were identified with more than one-quarter of
      these resulting in a nonsynonymous mutation. Affymetrix DNA microarrays and RNseq
      analysis were used to determine differences in gene expression in the evolved
      strains compared to the parental strain. It was established that approximately
      900 genes demonstrated significantly altered expression in the evolved strains
      relative to the parental strain. Many of these genes showed similar alterations
      in their expression in all three evolved strains. Interestingly, genes with
      altered expression in the three evolved strains included genes with a role in
      oxidative metabolism. Overall these results are consistent with the physiological
      observations of optimal growth with glucose as the carbon source. Namely, the
      decreased ethanol production suggest that the underlying metabolism switched from
      fermentation to respiration during the selection for optimal growth on glucose.

PMID- 23135696
TI  - Developmental changes and effect on intramuscular fat content of H-FABP and A
      FABP mRNA expression in pigs.
AB  - H-FABP and A-FABP genes are considered as candidates for intramuscular fat (IMF)
      accretion. The aim of the present study was to assess the expression of H-FABP
      and A-FABP genes in m. longissimus dorsi (LD) and liver tissues of Laiwu and
      Lulai Black pig populations of different body weight (BW). Eighty-four barrows at
      different BW (30, 40, 50, 60, 70, 80, 90 and 100 kg, n = 6 per group) of Laiwu
      Black pig (no 100 kg group) and Lulai Black pig (no 30 kg group) were used to
      study the development changes of A-FABP and H-FABP mRNA expression and their
      relationships to IMF content. The results showed that, in both breeds, the IMF
      content increased continuously with growing (P < 0.05). The expression of H-FABP
      and A-FABP genes also increased with growing in LD tissue (P < 0.05), and reached
      a peak at 50 and 70 kg BW in Laiwu and Lulai Black pig, respectively. However,
      this regularity was not observed in liver tissue in both breeds. A positive
      correlation was just found between the A-FABP mRNA expression level in LD tissue
      and IMF content and BW in both breeds (P < 0.05). In conclusion, the A-FABP gene
      is strongly related to the development and function of IMF accretion in pigs.

PMID- 23135697
TI  - Vitamin D, race, and experimental pain sensitivity in older adults with knee
      osteoarthritis.
AB  - OBJECTIVE: Low circulating serum levels of 25-hydroxyvitamin D (referred to
      hereafter as vitamin D) have been correlated with many health conditions,
      including chronic pain. Recent clinical practice guidelines define vitamin D
      levels <20 ng/ml as deficient and levels of 21-29 ng/ml as insufficient. Vitamin
      D insufficiency, including the most severe levels of deficiency, is more
      prevalent in black Americans. Ethnic and race group differences have been
      reported in both clinical and experimental pain, with black Americans reporting
      increased pain. The purpose of this study was to examine whether variations in
      vitamin D levels contribute to race differences in knee osteoarthritis pain.
      METHODS: The sample consisted of 94 participants (74% women), including 45 blacks
      and 49 whites with symptomatic knee osteoarthritis. Their average age was 55.8
      years (range 45-71 years). Participants completed a questionnaire on knee
      osteoarthritis symptoms and underwent quantitative sensory testing, including
      measures of sensitivity to heat-induced and mechanically induced pain. RESULTS:
      Blacks had significantly lower levels of vitamin D compared to whites,
      demonstrated greater clinical pain, and showed greater sensitivity to heat
      induced and mechanically induced pain. Low levels of vitamin D predicted
      increased experimental pain sensitivity, but did not predict self-reported
      clinical pain. Group differences in vitamin D levels significantly predicted
      group differences in heat pain and pressure pain thresholds at the index knee and
      ipsilateral forearm. CONCLUSION: These data demonstrate that race differences in
      experimental pain are mediated by differences in the vitamin D level. Vitamin D
      deficiency may be a risk factor for increased knee osteoarthritis pain in black
      Americans.

PMID- 23135698
TI  - Acid-sensing ion channels (ASICs) are differentially modulated by anions
      dependent on their subunit composition.
AB  - Acid-sensing ion channels (ASICs) are sodium channels gated by extracellular
      protons. ASIC1a channels possess intersubunit Cl(-)-binding sites in the
      extracellular domain, which are highly conserved between ASIC subunits. We
      previously found that anions modulate ASIC1a gating via these sites. Here we
      investigated the effect of anion substitution on native ASICs in rat sensory
      neurons and heterologously expressed ASIC2a and ASIC3 channels by whole cell
      patch clamp. Similar to ASIC1a, anions modulated the kinetics of desensitization
      of other ASIC channels. However, unlike ASIC1a, anions also modulated the pH
      dependence of activation. Moreover, the order of efficacy of different anions to
      modulate ASIC2a and -3 was very different from that of ASIC1a. More surprising,
      mutations of conserved residues that form an intersubunit Cl(-)-binding site in
      ASIC1a only partially abrogated the effects of anion modulation of ASIC2a and had
      no effect on anion modulation of ASIC3. The effects of anions on native ASICs in
      rat dorsal root ganglion neurons mimicked those in heterologously expressed
      ASIC1a/3 heteromeric channels. Our data show that anions modulate a variety of
      ASIC properties and are dependent on the subunit composition, and the mechanism
      of modulation for ASIC2a and -3 is distinct from that of ASIC1a. We speculate
      that modulation of ASIC gating by Cl(-) is a novel mechanism to sense shifts in
      extracellular fluid composition.

PMID- 23135699
TI  - SMB myosin heavy chain knockout enhances tonic contraction and reduces the rate
      of force generation in ileum and stomach antrum.
AB  - The role of SMA and SMB smooth muscle myosin heavy chain (MHC) isoforms in tonic
      and phasic contractions was studied in phasic (longitudinal ileum and stomach
      circular antrum) and tonic (stomach circular fundus) smooth muscle tissues of SMB
      knockout mice. Knocking out the SMB MHC gene eliminated SMB MHC protein
      expression and resulted in upregulation of the SMA MHC protein without altering
      the total MHC protein level. Switching from SMB to SMA MHC protein expression
      decreased the rate of the force transient and increased the sustained tonic force
      in SMB((-/-)) ileum and antrum with high potassium (KPSS) but not with carbachol
      (CCh) stimulation. The increased tonic contraction under the depolarized
      condition was not through changes in second messenger signaling pathways (PKC/CPI
      17 or Rho/ROCK signaling pathway) or LC(20) phosphorylation. Biochemical analyses
      showed that the expression of contractile regulatory proteins (MLCK, MLCP,
      PKCdelta, and CPI-17) did not change significantly in tissues tested except for
      PKCalpha protein expression being significantly decreased in the SMB((-/-))
      antrum. However, specifically activating PKCalpha with phorbol dibutyrate (PDBu)
      was not significantly different in knockout and wild-type tissues, with total
      force being a fraction of the force generation with KPSS or CCh stimulation in
      SMB((-/-)) ileum and antrum. Taken together, these data show removing the SMB MHC
      protein expression with a compensatory increase in the SMA MHC protein results in
      enhanced sustained KPSS-induced tonic contraction with a reduced rate of force
      generation in these phasic tissues.

PMID- 23135701
TI  - Caring about the other 47% of the water channels. Focus on "Basolateral targeting
      and microtubule-dependent transcytosis of the aquaporin-2 water channel".

PMID- 23135700
TI  - ROS production as a common mechanism of ENaC regulation by EGF, insulin, and IGF
      1.
AB  - The epithelial Na(+) channel (ENaC) is a key transporter participating in the
      fine tuning of Na(+) reabsorption in the nephron. ENaC activity is acutely
      upregulated by epidermal growth factor (EGF), insulin, and insulin-like growth
      factor-1 (IGF-1). It was also proposed that reactive oxygen species (ROS) have a
      stimulatory effect on ENaC. Here we studied whether effects of EGF, insulin, and
      IGF-1 correlate with ROS production in the mouse cortical collecting duct
      (mpkCCD(c14)) cells. Western blotting confirmed the expression of the NADPH
      oxidase complex subunits in these cells. Treatment of mpkCCD(c14) cells with EGF,
      insulin, or IGF-1 evoked an increase in ROS production as measured by CM-H(2)DCF
      DA fluorescence. ROS production caused by a xanthine-xanthine oxidase reaction
      also resulted in a significant elevation in short-circuit current through the
      mpkCCD(c14) monolayer. Transepithelial current measurements showed an acute
      increase of amiloride-sensitive current through the mpkCCD(c14) monolayer in
      response to EGF, insulin, or IGF-1. Pretreatment with the nonselective NADPH
      oxidase activity inhibitor apocynin blunted both ROS production and increase in
      ENaC-mediated current in response to these drugs. To further test whether NADPH
      oxidase subunits are involved in the effect of EGF, we used a stable M-1 cell
      line with a knockdown of Rac1, which is one of the key subunits of the NADPH
      oxidase complex, and measured amiloride-sensitive currents in response to EGF. In
      contrast to control cells, EGF had no effect in Rac1 knockdown cells. We
      hypothesize that EGF, insulin, and IGF-1 have a common stimulatory effect on ENaC
      mediated by ROS production.

PMID- 23135702
TI  - Grape seeds proanthocyanidin extract as a hepatic-reno-protective agent against
      gibberellic acid induced oxidative stress and cellular alterations.
AB  - The present study aims to investigate the heptonephro-protective effect of grape
      seeds proanthocyanidin extract (GSPE) against the risks induced by gibberellic
      acid (GA3) in male rats. The results recorded that GA3 caused a significant
      increase in total lipids, total cholesterol, triglycerides and LDL-C levels in
      serum, concomitant with a significant decrease in serum HDL-C. A significant
      increase in serum AST, ALT, urea and creatinine, while, a significant decrease in
      total protein content in serum was observed in rats given GA3. Hepatic and renal
      lipid peroxidation product (MDA) was significantly increased, meanwhile, total
      antioxidant capacity (TAC), glutathione, and catalase levels were significantly
      decreased. In addition, there was a negative change in liver structure including
      dilatation in the central veins with degeneration of endothelium cells and
      cellular injury around the veins as well as in the kidney structure such as
      lesion in both glomeruli and tubules, detachment of the Malpighian corpuscles
      from the Bowman's capsule's epithelium, shrinkage in the glomerular capillary
      network. However, almost all of these adverse effects seemed to be ameliorated by
      oral administration of GSPE with GA3 to rats for 2 month indicating the
      protective effect of grape seeds GSPE on GA3 induced oxidative stress in rats. 

PMID- 23135703
TI  - Phenol red inhibits chondrogenic differentiation and affects osteogenic
      differentiation of human mesenchymal stem cells in vitro.
AB  - The purpose with this study was to investigate the effect of phenol red (PR) on
      chondrogenic and osteogenic differentiation of human mesenchymal stem cells
      (hMSCs). hMSCs were differentiated into chondrogenic and osteogenic directions in
      DMEM with and without PR for 2, 7, 14, 21, and 28 days. Gene expression of
      chondrogenic and osteogenic markers were analyzed by RT-qPCR. The presence of
      proteoglycans was visualized histologically. Osteogenic matrix deposition and
      mineralization were examined measuring the alkaline phophatase activity and
      calcium deposition. During chondrogenic differentiation PR decreased sox9,
      collagen type 2, aggrecan on day 14 and 21 (P < 0.05), and proteoglycan synthesis
      on day 21 and 28. Collagen type 10 was decreased on day 21 (P < 0.05). During
      osteogenic differentiation PR increased alkaline phosphatase on day 7 while
      decreased on day 21 (P < 0.05). PR increased collagen type 1 on day 7, 14, and
      day 21 (P < 0.05). The alkaline phosphatase activity was increased after 2, 7,
      and 14 days (P < 0.05). The deposition of calcium was decreased on day 21 (P <
      0.05). Our results indicate that PR should be removed from the culture media when
      differentiating hMSCs into chondrogenic and osteogenic directions due to the
      effects on these differentiation pathways.

PMID- 23135704
TI  - The microtubule targeting agent PBOX-15 inhibits integrin-mediated cell adhesion
      and induces apoptosis in acute lymphoblastic leukaemia cells.
AB  - Although recent decades have seen an improved cure rate for newly diagnosed
      paediatric acute lymphoplastic leukaemia (ALL), the treatment options for adult
      ALL, T-cell ALL (T-ALL) and relapsed disease remain poor. We have developed a
      novel series of pyrrolo-1,5-benzoxazepine (PBOX) compounds and established their
      anticancer efficacy in a variety of human tumour cell types. Here, we demonstrate
      that PBOX-15 inhibits cell growth, and induces G2/M cell cycle arrest and
      apoptosis in both T-ALL and B-cell ALL (B-ALL) cells. In addition, prior to PBOX
      15-induced apoptosis, PBOX-15 decreases ALL cell adhesion, spreading and
      migration. Concurrently, PBOX-15 differentially down-regulates beta1-, beta2- and
      alpha4-integrin expression in ALL cells and significantly decreases integrin
      mediated cell attachment. PBOX-15 interferes with the lateral mobility and
      clustering of integrins in both B-ALL and T-ALL cells. These data suggest that
      PBOX-15 is not only effective in inducing apoptosis in ALL cells, but also has
      the potential to disrupt integrin-mediated adhesion of malignant lymphocytes,
      which represents a novel avenue for regulating leukaemic cell homing and
      migration.

PMID- 23135705
TI  - Association of monocyte chemoattractant protein-1 -2518A>G polymorphism with
      occurrence, severity, and outcome in ischemic stroke.
AB  - Monocyte chemoattractant protein-1 (MCP-1) is implicated in promoting
      atherosclerotic diseases, including stroke. Therefore, several studies have
      investigated the association between variants of the MCP-1 gene and risk of
      atherosclerotic diseases. We sought to determine the occurrence of MCP-1 -2518A>G
      polymorphism in patients with ischemic stroke (IS), and studied its association
      with the severity of disease and functional outcome after an acute IS. One
      hundred and forty-five consecutive patients with first ever IS and 145 age- and
      sex-matched control subjects were recruited. Stroke severity and functional
      outcome were assessed on admission and at one month post-stroke, respectively.
      Genotyping for the MCP-1 -2518A>G polymorphism was performed by a polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP). No
      significant difference in the frequency of MCP-1 -2518A>G genotypes between IS
      patients and controls was found, with OR = 0.69 (95 % CI 0.46-1.04, P = 0.08).
      Moreover, carriage of the G allele was not associated with stroke severity
      (Scandinavian stroke scale score 33.1 vs. 32.5, respectively, P = 0.71), or poor
      outcome at 1 month post-stroke (63.9 vs. 59.7 %, respectively, P = 0.61). In
      conclusion, we were unable to demonstrate a significant association of the MCP-1 
      2518A>G gene polymorphism with IS occurrence, severity or functional outcome in a
      Caucasian population. However, larger studies are necessary to fully elucidate
      the role of this polymorphism in IS.

PMID- 23135706
TI  - Nutrition support safe practices. Editor's note.

PMID- 23135707
TI  - The impact of implementation of a nutrition support algorithm on nutrition care
      outcomes in an intensive care unit.
AB  - BACKGROUND: A nutrition support algorithm is an operational version of a
      guideline that is adapted to local requirements and easy to apply in clinical
      practice. The purpose of this study was to determine the impact of implementing a
      nutrition support algorithm on nutrition care outcomes in an intensive care unit
      (ICU) in Switzerland without a designated dietitian. METHODS: The retrospective
      study included data collection on 2 cohorts of critically ill patients before (n
      = 56) and after (n = 56) implementation of a nutrition support algorithm based on
      the guidelines published by the Society of Critical Care Medicine and the
      American Society for Parenteral and Enteral Nutrition guidelines. RESULTS: There
      were significant differences between groups for the mean delivery of total energy
      in the pre- vs postimplementation group (909 +/- 444 vs 1097 +/- 420 kcal/d; P =
      .023) and mean delivery of protein per day (35 +/- 17.9 vs 59.1 +/- 27.3 g; P <
      .001). For patients staying at least 7 days in the ICU, the cumulative energy
      deficit decreased from -5664 +/- 3613 kcal in the preimplementation group to 
      2972 +/- 2420 kcal (P = .011) in the postimplementation group. No significant
      differences in the route of feeding and timing of enteral nutrition initiation
      were found. CONCLUSIONS: Implementation of a nutrition support algorithm resulted
      in improved provision of energy and protein delivery. This may be further
      improved with routine nutrition assessment by a dietitian or a designated
      nutrition support team.

PMID- 23135708
TI  - The adenoviral oncogene E1A-13S interacts with a specific isoform of the tumor
      suppressor PML to enhance viral transcription.
AB  - PML nuclear bodies (PML NBs), also called ND10, are matrix-bound nuclear
      structures that have been implicated in a variety of functions, including DNA
      repair, transcriptional regulation, protein degradation, and tumor suppression.
      These domains are also known for their potential to mediate an intracellular
      defense mechanism against many virus types. This is likely why they are targeted
      and subsequently manipulated by numerous viral proteins. Paradoxically, the
      genomes of various DNA viruses become associated with PML NBs, and initial sites
      of viral transcription/replication centers are often juxtaposed to these domains.
      The question is why viruses start their transcription and replication next to
      their supposed antagonists. Here, we report that PML NBs are targeted by the
      adenoviral (Ad) transactivator protein E1A-13S. Alternatively spliced E1A
      isoforms (E1A-12S and E1A-13S) are the first proteins expressed upon Ad
      infection. E1A-13S is essential for activating viral transcription in the early
      phase of infection. Coimmunoprecipitation assays showed that E1A-13S
      preferentially interacts with only one (PML-II) of at least six nuclear human PML
      isoforms. Deletion mapping located the interaction site within E1A conserved
      region 3 (CR3), which was previously described as the transcription factor
      binding region of E1A-13S. Indeed, cooperation with PML-II enhanced E1A-mediated
      transcriptional activation, while deleting the SUMO-interacting motif (SIM) of
      PML proved even more effective. Our results suggest that in contrast to PML NB
      associated antiviral defense, PML-II may help transactivate viral gene expression
      and therefore play a novel role in activating Ad transcription during the early
      viral life cycle.

PMID- 23135709
TI  - Expression of prototype foamy virus pol as a Gag-Pol fusion protein does not
      change the timing of reverse transcription.
AB  - Foamy viruses are retroviruses whose Pol protein is synthesized without Gag from
      a spliced mRNA. Unlike orthoretroviruses, reverse transcription occurs during
      viral assembly, leading to DNA-containing virions. When prototype foamy virus Pol
      is expressed as an orthoretroviral-like Gag-Pol fusion protein, reverse
      transcription also occurs late in viral replication, as measured by the timing of
      reverse transcriptase sensitivity to the inhibitor 3'-azido-3'deoxythymidine
      (AZT). Thus, timing of reverse transcription is intrinsic to Pol itself.

PMID- 23135710
TI  - Engagement of the ATR-dependent DNA damage response at the human papillomavirus
      18 replication centers during the initial amplification.
AB  - We have previously demonstrated that the human papillomavirus (HPV) genome
      replicates effectively in U2OS cells after transfection using electroporation.
      The transient extrachromosomal replication, stable maintenance, and late
      amplification of the viral genome could be studied for high- and low-risk mucosal
      and cutaneous papillomaviruses. Recent findings indicate that the cellular DNA
      damage response (DDR) is activated during the HPV life cycle and that the viral
      replication protein E1 might play a role in this process. We used a U2OS cell
      based system to study E1-dependent DDR activation and the involvement of these
      pathways in viral transient replication. We demonstrated that the E1 protein
      could cause double-strand DNA breaks in the host genome by directly interacting
      with DNA. This activity leads to the induction of an ATM-dependent signaling
      cascade and cell cycle arrest in the S and G(2) phases. However, the transient
      replication of HPV genomes in U2OS cells induces the ATR-dependent pathway, as
      shown by the accumulation of gammaH2AX, ATR-interacting protein (ATRIP), and
      topoisomerase IIbeta-binding protein 1 (TopBP1) in viral replication centers.
      Viral oncogenes do not play a role in this activation, which is induced only
      through DNA replication or by replication proteins E1 and E2. The ATR pathway in
      viral replication centers is likely activated through DNA replication stress and
      might play an important role in engaging cellular DNA repair/recombination
      machinery for effective replication of the viral genome upon active
      amplification.

PMID- 23135711
TI  - Viral genome methylation differentially affects the ability of BZLF1 versus BRLF1
      to activate Epstein-Barr virus lytic gene expression and viral replication.
AB  - The Epstein-Barr virus (EBV) immediate-early proteins BZLF1 and BRLF1 can both
      induce lytic EBV reactivation when overexpressed in latently infected cells.
      Although EBV genome methylation is required for BZLF1-mediated activation of
      lytic gene expression, the effect of viral genome methylation on BRLF1-mediated
      viral reactivation has not been well studied. Here, we have compared the effect
      of viral DNA methylation on BZLF1- versus BRLF1-mediated activation of lytic EBV
      gene transcription and viral genome replication. We show that most early lytic
      viral promoters are preferentially activated by BZLF1 in the methylated form,
      while methylation decreases the ability of BRLF1 to activate most early lytic
      promoters, as well as the BLRF2 late viral promoter. Moreover, methylation of
      bacmid constructs containing the EBV genome enhances BZLF1-mediated, but
      decreases BRLF1-mediated, early lytic gene expression. Methylation of viral
      promoter DNA does not affect BRLF1 binding to a variety of different CpG
      containing BRLF1 binding motifs (RREs) in vitro or in vivo. However, BRLF1
      preferentially induces H3K9 histone acetylation of unmethylated promoters in
      vivo. The methylated and unmethylated forms of an oriLyt-containing plasmid
      replicate with similar efficiency when transfected into EBV-positive cells that
      express the essential viral replication proteins in trans. Most importantly, we
      demonstrate that lytic viral gene expression and replication can be induced by
      BRLF1, but not BZLF1, expression in an EBV-positive telomerase-immortalized
      epithelial cell line (NOKs-Akata) in which lytic viral gene promoters remain
      largely unmethylated. These results suggest that the unmethylated form of the EBV
      genome can undergo viral reactivation and replication in a BRLF1-dependent
      manner.

PMID- 23135712
TI  - Influenza virus induces apoptosis via BAD-mediated mitochondrial dysregulation.
AB  - Influenza virus infection results in host cell death and major tissue damage.
      Specific components of the apoptotic pathway, a signaling cascade that ultimately
      leads to cell death, are implicated in promoting influenza virus replication. BAD
      is a cell death regulator that constitutes a critical control point in the
      intrinsic apoptosis pathway, which occurs through the dysregulation of
      mitochondrial outer membrane permeabilization and the subsequent activation of
      downstream apoptogenic factors. Here we report a novel proviral role for the
      proapoptotic protein BAD in influenza virus replication. We show that influenza
      virus-induced cytopathology and cell death are considerably inhibited in BAD
      knockdown cells and that both virus replication and viral protein production are
      dramatically reduced, which suggests that virus-induced apoptosis is BAD
      dependent. Our data showed that influenza viruses induced phosphorylation of BAD
      at residues S112 and S136 in a temporal manner. Viral infection also induced BAD
      cleavage, late in the viral life cycle, to a truncated form that is reportedly a
      more potent inducer of apoptosis. We further demonstrate that knockdown of BAD
      resulted in reduced cytochrome c release and suppression of the intrinsic
      apoptotic pathway during influenza virus replication, as seen by an inhibition of
      caspases-3, caspase-7, and procyclic acidic repetitive protein (PARP) cleavage.
      Our data indicate that influenza viruses carefully modulate the activation of the
      apoptotic pathway that is dependent on the regulatory function of BAD and that
      failure of apoptosis activation resulted in unproductive viral replication.

PMID- 23135713
TI  - HIV-1 resistance to maraviroc conferred by a CD4 binding site mutation in the
      envelope glycoprotein gp120.
AB  - Maraviroc (MVC) is a CCR5 antagonist that inhibits HIV-1 entry by binding to the
      coreceptor and inducing structural alterations in the extracellular loops. In
      this study, we isolated MVC-resistant variants from an HIV-1 primary isolate that
      arose after 21 weeks of tissue culture passage in the presence of inhibitor.
      gp120 sequences from passage control and MVC-resistant cultures were cloned into
      NL4-3 via yeast-based recombination followed by sequencing and drug
      susceptibility testing. Using 140 clones, three mutations were linked to MVC
      resistance, but none appeared in the V3 loop as was the case with previous HIV-1
      strains resistant to CCR5 antagonists. Rather, resistance was dependent upon a
      single mutation in the C4 region of gp120. Chimeric clones bearing this N425K
      mutation replicated at high MVC concentrations and displayed significant shifts
      in 50% inhibitory concentrations (IC(50)s), characteristic of resistance to all
      other antiretroviral drugs but not typical of MVC resistance. Previous reports on
      MVC resistance describe an ability to use a drug-bound form of the receptor,
      leading to reduction in maximal drug inhibition. In contrast, our structural
      models on K425 gp120 suggest that this resistant mutation impacts CD4
      interactions and highlights a novel pathway for MVC resistance.

PMID- 23135714
TI  - Visualizing a complete Siphoviridae member by single-particle electron
      microscopy: the structure of lactococcal phage TP901-1.
AB  - Tailed phages are genome delivery machines exhibiting unequaled efficiency
      acquired over more than 3 billion years of evolution. Siphophages from the P335
      and 936 families infect the Gram-positive bacterium Lactococcus lactis using
      receptor-binding proteins anchored to the host adsorption apparatus (baseplate).
      Crystallographic and electron microscopy (EM) studies have shed light on the
      distinct adsorption strategies used by phages of these two families, suggesting
      that they might also rely on different infection mechanisms. Here, we report
      electron microscopy reconstructions of the whole phage TP901-1 (P335 species) and
      propose a composite EM model of this gigantic molecular machine. Our results
      suggest conservation of structural proteins among tailed phages and add to the
      growing body of evidence pointing to a common evolutionary origin for these
      virions. Finally, we propose that host adsorption apparatus architectures have
      evolved in correlation with the nature of the receptors used during infection.

PMID- 23135715
TI  - Requirement of the N-terminal activation domain of herpes simplex virus ICP4 for
      viral gene expression.
AB  - ICP4 is the major activator of herpes simplex virus (HSV) transcription. Previous
      studies have defined several regions of ICP4 that are important for viral gene
      expression, including a DNA binding domain and transactivation domains that are
      contained in the C-terminal and N-terminal 520 and 274 amino acids, respectively.
      Here we show that the N-terminal 210 amino acids of ICP4 are required for
      interactions with components of TFIID and mediator and, as a consequence, are
      necessary for the activation of viral genes. A mutant of ICP4 deleted for amino
      acids 30 to 210, d3-10, was unable to complement an ICP4 null virus at the level
      of viral replication. This was the result of a severe deficiency in viral gene
      and protein expression. The absence of viral gene expression coincided with a
      defect in the recruitment of RNA polymerase II to a representative early promoter
      (thymidine kinase [TK]). Affinity purification experiments demonstrated that d3
      10 ICP4 was not found in complexes with components of TFIID and mediator,
      suggesting that the defect in RNA polymerase II (Pol II) recruitment was the
      result of ablated interactions between d3-10 and TFIID and mediator.
      Complementation assays suggested that the N-terminal and C-terminal regions of
      ICP4 cooperate to mediate gene expression. The complementation was the result of
      the formation of more functional heterodimers, which restored the ability of the
      d3-10-containing molecules to interact with TFIID. Together, these studies
      suggest that the N terminus contains a true activation domain, mediating
      interactions with TFIID, mediator, and perhaps other transcription factors, and
      that the C terminus of the molecule contains activities that augment the
      functions of the activation domain.

PMID- 23135716
TI  - The replication defect of ICP0-null mutant herpes simplex virus 1 can be largely
      complemented by the combined activities of human cytomegalovirus proteins IE1 and
      pp71.
AB  - Herpes simplex virus 1 (HSV-1) immediate-early protein ICP0 is required for
      efficient lytic infection and productive reactivation from latency and induces
      derepression of quiescent viral genomes. Despite being unrelated at the sequence
      level, ICP0 and human cytomegalovirus proteins IE1 and pp71 share some functional
      similarities in their abilities to counteract antiviral restriction mediated by
      components of cellular nuclear structures known as ND10. To investigate the
      extent to which IE1 and pp71 might substitute for ICP0, cell lines were developed
      that express either IE1 or pp71, or both together, in an inducible manner. We
      found that pp71 dissociated the hDaxx-ATRX complex and inhibited accumulation of
      these proteins at sites juxtaposed to HSV-1 genomes but had no effect on the
      promyelocytic leukemia protein (PML) or Sp100. IE1 caused loss of the small
      ubiquitin-like modifier (SUMO)-conjugated forms of PML and Sp100 and inhibited
      the recruitment of these proteins to HSV-1 genome foci but had little effect on
      hDaxx or ATRX in these assays. Both IE1 and pp71 stimulated ICP0-null mutant
      plaque formation, but neither to the extent achieved by ICP0. The combination of
      IE1 and pp71, however, inhibited recruitment of all ND10 proteins to viral genome
      foci, stimulated ICP0-null mutant HSV-1 plaque formation to near wild-type
      levels, and efficiently induced derepression of quiescent HSV-1 genomes. These
      results suggest that ND10-related intrinsic resistance results from the additive
      effects of several ND10 components and that the effects of IE1 and pp71 on
      subsets of these components combine to mirror the overall activities of ICP0.

PMID- 23135717
TI  - Independent activation of hepatitis B virus biosynthesis by retinoids, peroxisome
      proliferators, and bile acids.
AB  - In the human hepatoma cell line HepG2, retinoic acid, clofibric acid, and bile
      acid treatment can only modestly increase hepatitis B virus (HBV) biosynthesis.
      Utilizing the human embryonic kidney cell line 293T, it was possible to
      demonstrate that the retinoid X receptor alpha (RXRalpha) plus its ligand can
      support viral biosynthesis independently of additional nuclear receptors. In
      addition, RXRalpha/peroxisome proliferator-activated receptor alpha (PPARalpha)
      and RXRalpha/farnesoid X receptor alpha (FXRalpha) heterodimeric nuclear
      receptors can also mediate ligand-dependent HBV transcription and replication
      when activated by clofibric acid and bile acid, respectively, independently of a
      requirement for the ligand-dependent activation of RXRalpha. These observations
      indicate that there are at least three possible modes of ligand-mediated
      activation of HBV transcription and replication existing within hepatocytes,
      suggesting that multiple independent mechanisms control viral production in the
      livers of infected individuals.

PMID- 23135718
TI  - Repeated exposure to trace amounts of woodchuck hepadnavirus induces molecularly
      evident infection and virus-specific T cell response in the absence of
      serological infection markers and hepatitis.
AB  - Exposure to multiple small doses of hepatitis B virus (HBV) is a frequent
      occurrence in high-risk groups, including close relatives of infected
      individuals, primary care givers, and intravenous drug users. It remains
      uncertain whether such repeated contact may culminate in a symptomatic infection
      coinciding with hepatitis in individuals not immunoprotected. In this study, we
      evaluated consequences of multiple exposures to small, liver-nonpathogenic
      amounts of infectious hepadnavirus in the woodchuck model of hepatitis B. Virus
      naive animals were intravenously injected with 6 weekly doses of 110 DNase
      digestion-protected virions of woodchuck hepatitis virus (WHV), injected again
      with 6 weekly 110-virion doses after 7.5 months, and then challenged or not with
      a liver-pathogenic dose of 1.1 * 10(6) virions of the same inoculum. The data
      revealed that two rounds of such repeated exposure did not result in
      serologically evident infection or hepatitis. However, a low-level WHV DNA
      positive infection accompanied by a WHV-specific T cell response in the absence
      of antiviral antibody reactivity was established. The kinetics of the virus
      specific and mitogen-induced (generalized) T cell responses and the inability to
      induce immunoprotection against challenge with a large, liver-pathogenic virus
      dose were closely comparable to those previously reported for occult infection
      initiated by a single liver-nonpathogenic dose of WHV. Thus, repeated exposures
      to small quantities of hepadnavirus induce molecularly evident but serologically
      silent infection that does not culminate in hepatitis or generate immune
      protection. The findings imply that the HBV-specific T cell response encountered
      in the absence of serological markers of infection likely reflects ongoing occult
      infection.

PMID- 23135719
TI  - Highly attenuated recombinant vesicular stomatitis virus VSV-12'GFP displays
      immunogenic and oncolytic activity.
AB  - Vesicular stomatitis virus (VSV) has shown considerable promise both as an
      immunization vector and as an oncolytic virus. In both applications, an important
      concern is the safety profile of the virus. To generate a highly attenuated
      virus, we added two reporter genes to the 3' end of the VSV genome, thereby
      shifting the NPMGL genes from positions 1 to 5 to positions 3 to 7. The resulting
      virus (VSV-12'GFP) was highly attenuated, generating smaller plaques than four
      other attenuated VSVs. In one-step growth curves, VSV-12'GFP displayed the
      slowest growth kinetics. The mechanism of attenuation appears to be due to
      reduced expression of VSV genes downstream of the reporter genes, as suggested by
      a 10.4-fold reduction in L-protein RNA transcript. Although attenuated, VSV
      12'GFP was highly effective at generating an immune response, indicated by a high
      titer antibody response against the green fluorescent protein (GFP) expressed by
      the virus. Although VSV-12'GFP was more attenuated than other VSVs on both normal
      and cancer cells, it nonetheless showed a greater level of infection of human
      cancer cells (glioma and melanoma) than of normal cells, and this effect was
      magnified in glioma by interferon application, indicating selective oncolysis.
      Intravenous VSV-12'GFP selectively infected human gliomas implanted into SCID
      mice subcutaneously or intracranially. All postnatal day 16 mice given intranasal
      VSV-12'GFP survived, whereas only 10% of those given VSV-G/GFP survived,
      indicating reduced neurotoxicity. Intratumoral injection of tumors with VSV
      12'GFP dramatically suppressed tumor growth and enhanced survival. Together these
      data suggest this recombinant virus merits further study for its oncolytic and
      vaccine potential.

PMID- 23135720
TI  - hsp70 and a novel axis of type I interferon-dependent antiviral immunity in the
      measles virus-infected brain.
AB  - The major inducible 70-kDa heat shock protein (hsp70) is host protective in a
      mouse model of measles virus (MeV) brain infection. Transgenic constitutive
      expression of hsp70 in neurons, the primary target of MeV infection, abrogates
      neurovirulence in neonatal H-2(d) congenic C57BL/6 mice. A significant level of
      protection is retained after depletion of T lymphocytes, implicating innate
      immune mechanisms. The focus of the present work was to elucidate the basis for
      hsp70-dependent innate immunity using this model. Transcriptome analysis of
      brains from transgenic (TG) and nontransgenic (NT) mice 5 days after infection
      identified type I interferon (IFN) signaling, macrophage activation, and antigen
      presentation as the main differences linked to survival. The pivotal role of type
      I IFN in hsp70-mediated protection was demonstrated in mice with a genetically
      disrupted type I IFN receptor (IFNAR(-/-)), where IFNAR(-/-) eliminated the
      difference in survival between TG and NT mice. Brain macrophages, not neurons,
      are the predominant source of type I IFN in the virus-infected brain, and in
      vitro studies provided a mechanistic basis by which MeV-infected neurons can
      induce IFN-beta in uninfected microglia in an hsp70-dependent manner. MeV
      infection induced extracellular release of hsp70 from mouse neuronal cells that
      constitutively express hsp70, and extracellular hsp70 induced IFN-beta
      transcription in mouse microglial cells through Toll-like receptors 2 and 4.
      Collectively, our results support a novel axis of type I IFN-dependent antiviral
      immunity in the virus-infected brain that is driven by hsp70.

PMID- 23135721
TI  - Mucosal tissue tropism and dissemination of HIV-1 subtype B acute envelope
      expressing chimeric virus.
AB  - Human immunodeficiency virus type 1 (HIV-1) transmission results from infection
      with one or a small number of variants from the donor quasispecies.
      Transmitted/founder (T/F) viruses have recently been identified from acutely
      infected patients, but the way in which they interact with primary targets of HIV
      1 infection is poorly understood. We have conducted a biological characterization
      of a panel of subtype B T/F acute and chronic envelope (Env)-expressing chimeric
      virus in primary human target cells and mucosal tissues. Both acute and chronic
      Envs preferentially replicated in peripheral blood mononuclear cells (PBMC) and a
      CD4 T-cell line compared to monocyte-derived macrophages, or dendritic cells
      (DC). In a model of trans infection from monocyte-derived dendritic cells to T
      cells, chimeric virus from acute Envs achieved significantly lower titers
      compared to chronic Envs. Challenge of primary human mucosal tissues revealed
      significantly higher levels of replication in chronic Env-expressing virus in
      rectal tissue compared to cervical and penile tissues and enhanced replication in
      tonsillar tissue relative to acute Envs. In agreement with data from the DC to T
      cell trans infection assay, chronic Env-chimeric virus pools were transmitted
      more efficiently by migratory cells from cervical and penile tissues to CD4(+) T
      cells than individual acute Env chimeras. These data indicate that virus with HIV
      1 Envs of transmitted acute infections preferentially replicate in T cells rather
      than macrophages or dendritic cells and are less efficiently transmitted from
      antigen-presenting cells to CD4 T cells than chronic Envs. Such properties
      together with chemokine (C-C motif) receptor 5 (CCR5) use may confer an advantage
      for transmission.

PMID- 23135722
TI  - Gangliosides have a functional role during rotavirus cell entry.
AB  - Cell entry of rotaviruses is a complex process, which involves sequential
      interactions with several cell surface molecules. Among the molecules implicated
      are gangliosides, glycosphingolipids with one or more sialic acid (SA) residues.
      The role of gangliosides in rotavirus cell entry was studied by silencing the
      expression of two key enzymes involved in their biosynthesis--the UDP
      glucose:ceramide glucosyltransferase (UGCG), which transfers a glucose molecule
      to ceramide to produce glucosylceramide GlcCer, and the lactosyl ceramide-alpha
      2,3-sialyl transferase 5 (GM3-s), which adds the first SA to lactoceramide
      producing ganglioside GM3. Silencing the expression of both enzymes resulted in
      decreased ganglioside levels (as judged by GM1a detection). Four rotavirus
      strains tested (human Wa, simian RRV, porcine TFR-41, and bovine UK) showed a
      decreased infectivity in cells with impaired ganglioside synthesis; however,
      their replication after bypassing the entry step was not affected, confirming the
      importance of gangliosides for cell entry of the viruses. Interestingly, viral
      binding to the cell surface was not affected in cells with inhibited ganglioside
      synthesis, but the infectivity of all strains tested was inhibited by
      preincubation of gangliosides with virus prior to infection. These data suggest
      that rotaviruses can attach to cell surface in the absence of gangliosides but
      require them for productive cell entry, confirming their functional role during
      rotavirus cell entry.

PMID- 23135723
TI  - Host mTORC1 signaling regulates andes virus replication.
AB  - Hantavirus pulmonary syndrome (HPS) is a severe respiratory disease characterized
      by pulmonary edema, with fatality rates of 35 to 45%. Disease occurs following
      infection with pathogenic New World hantaviruses, such as Andes virus (ANDV),
      which targets lung microvascular endothelial cells. During replication, the virus
      scavenges 5'-m(7)G caps from cellular mRNA to ensure efficient translation of
      viral proteins by the host cell cap-dependent translation machinery. In cells,
      the mammalian target of rapamycin (mTOR) regulates the activity of host cap
      dependent translation by integrating amino acid, energy, and oxygen availability
      signals. Since there is no approved pharmacological treatment for HPS, we
      investigated whether inhibitors of the mTOR pathway could reduce hantavirus
      infection. Here, we demonstrate that treatment with the FDA-approved rapamycin
      analogue temsirolimus (CCI-779) blocks ANDV protein expression and virion release
      but not entry into primary human microvascular endothelial cells. This effect was
      specific to viral proteins, as temsirolimus treatment did not block host protein
      synthesis. We confirmed that temsirolimus targeted host mTOR complex 1 (mTORC1)
      and not a viral protein, as knockdown of mTORC1 and mTORC1 activators but not
      mTOR complex 2 components reduced ANDV replication. Additionally, primary
      fibroblasts from a patient with tuberous sclerosis exhibited increased mTORC1
      activity and increased ANDV protein expression, which were blocked following
      temsirolimus treatment. Finally, we show that ANDV glycoprotein Gn colocalized
      with mTOR and lysosomes in infected cells. Together, these data demonstrate that
      mTORC1 signaling regulates ANDV replication and suggest that the hantavirus Gn
      protein may modulate mTOR and lysosomal signaling during infection, thus
      bypassing the cellular regulation of translation.

PMID- 23135724
TI  - Characterization of the nonstructural proteins of the bocavirus minute virus of
      canines.
AB  - We present a detailed characterization of a single-cycle infection of the
      bocavirus minute virus of canines (MVC) in canine WRD cells. This has allowed
      identification of an additional smaller NS protein that derives from an mRNA
      spliced within the NS gene that had not been previously reported. In addition, we
      have identified a role for the viral NP1 protein during infection. NP1 is
      required for read-through of the MVC internal polyadenylation site and, thus,
      access of the capsid gene by MVC mRNAs. Although the mechanism of NP1's action
      has not yet been fully elucidated, it represents the first parvovirus protein to
      be implicated directly in viral RNA processing.

PMID- 23135725
TI  - Biogenesis of the vaccinia virus membrane: genetic and ultrastructural analysis
      of the contributions of the A14 and A17 proteins.
AB  - Vaccinia virus membrane biogenesis requires the A14 and A17 proteins. We show
      here that both proteins can associate with membranes co- but not
      posttranslationally, and we perform a structure function analysis of A14 and A17
      using inducible recombinants. In the absence of A14, electron-dense virosomes and
      distinct clusters of small vesicles accumulate; in the absence of A17, small
      vesicles form a corona around the virosomes. When the proteins are induced at 12
      h postinfection (hpi), crescents appear at the periphery of the electron-dense
      virosomes, with the accumulated vesicles likely contributing to their formation.
      A variety of mutant alleles of A14 and A17 were tested for their ability to
      support virion assembly. For A14, biologically important motifs within the N
      terminal or central loop region affected crescent maturation and the immature
      virion (IV)->mature virion (MV) transition. For A17, truncation or mutation of
      the N terminus of A17 engendered a phenotype consistent with the N terminus of
      A17 recruiting the D13 scaffold protein to nascent membranes. When N-terminal
      processing was abrogated, virions attempted to undergo the IV-to-MV transition
      without removing the D13 scaffold and were therefore noninfectious and
      structurally aberrant. Finally, we show that A17 is phosphorylated exclusively
      within the C-terminal tail and that this region is a direct substrate of the
      viral F10 kinase. In vivo, the biological competency of A17 was reduced by
      mutations that prevented its serine-threonine phosphorylation and restored by
      phosphomimetic substitutions. Precleavage of the C terminus or abrogation of its
      phosphorylation diminished the IV->MV maturation; a block to cleavage spared
      virion maturation but compromised the yield of infectious virus.

PMID- 23135726
TI  - Nucleolar trafficking of the mouse mammary tumor virus gag protein induced by
      interaction with ribosomal protein L9.
AB  - The mouse mammary tumor virus (MMTV) Gag protein directs the assembly in the
      cytoplasm of immature viral capsids, which subsequently bud from the plasma
      membranes of infected cells. MMTV Gag localizes to discrete cytoplasmic foci in
      mouse mammary epithelial cells, consistent with the formation of cytosolic
      capsids. Unexpectedly, we also observed an accumulation of Gag in the nucleoli of
      infected cells derived from mammary gland tumors. To detect Gag-interacting
      proteins that might influence its subcellular localization, a yeast two-hybrid
      screen was performed. Ribosomal protein L9 (RPL9 or L9), an essential component
      of the large ribosomal subunit and a putative tumor suppressor, was identified as
      a Gag binding partner. Overexpression of L9 in cells expressing the MMTV(C3H)
      provirus resulted in specific, robust accumulation of Gag in nucleoli. Forster
      resonance energy transfer (FRET) and coimmunoprecipitation analyses demonstrated
      that Gag and L9 interact within the nucleolus, and the CA domain was the major
      site of interaction. In addition, the isolated NC domain of Gag localized to the
      nucleolus, suggesting that it contains a nucleolar localization signal (NoLS). To
      determine whether L9 plays a role in virus assembly, small interfering RNA
      (siRNA)-mediated knockdown was performed. Although Gag expression was not reduced
      with L9 knockdown, virus production was significantly impaired. Thus, our data
      support the hypothesis that efficient MMTV particle assembly is dependent upon
      the interaction of Gag and L9 in the nucleoli of infected cells.

PMID- 23135727
TI  - Human T cell leukemia virus type 2 tax-mediated NF-kappaB activation involves a
      mechanism independent of Tax conjugation to ubiquitin and SUMO.
AB  - Permanent activation of the NF-kappaB pathway by the human T cell leukemia virus
      type 1 (HTLV-1) Tax (Tax1) viral transactivator is a key event in the process of
      HTLV-1-induced T lymphocyte immortalization and leukemogenesis. Although encoding
      a Tax transactivator (Tax2) that activates the canonical NF-kappaB pathway, HTLV
      2 does not cause leukemia. These distinct pathological outcomes might be related,
      at least in part, to distinct NF-kappaB activation mechanisms. Tax1 has been
      shown to be both ubiquitinated and SUMOylated, and these two modifications were
      originally proposed to be required for Tax1-mediated NF-kappaB activation. Tax1
      ubiquitination allows recruitment of the IKK-gamma/NEMO regulatory subunit of the
      IKK complex together with Tax1 into centrosome/Golgi-associated cytoplasmic
      structures, followed by activation of the IKK complex and RelA/p65 nuclear
      translocation. Herein, we compared the ubiquitination, SUMOylation, and
      acetylation patterns of Tax2 and Tax1. We show that, in contrast to Tax1, Tax2
      conjugation to endogenous ubiquitin and SUMO is barely detectable while both
      proteins are acetylated. Importantly, Tax2 is neither polyubiquitinated on lysine
      residues nor ubiquitinated on its N-terminal residue. Consistent with these
      observations, Tax2 conjugation to ubiquitin and Tax2-mediated NF-kappaB
      activation is not affected by overexpression of the E2 conjugating enzyme Ubc13.
      We further demonstrate that a nonubiquitinable, non-SUMOylable, and nonacetylable
      Tax2 mutant retains a significant ability to activate transcription from a NF
      kappaB-dependent promoter after partial activation of the IKK complex and
      induction of RelA/p65 nuclear translocation. Finally, we also show that Tax2 does
      not interact with TRAF6, a protein that was shown to positively regulate Tax1
      mediated activation of the NF-kappaB pathway.

PMID- 23135728
TI  - Humoral immunity to smallpox vaccines and monkeypox virus challenge: proteomic
      assessment and clinical correlations.
AB  - Despite the eradication of smallpox, orthopoxviruses (OPV) remain public health
      concerns. Efforts to develop new therapeutics and vaccines for smallpox continue
      through their evaluation in animal models despite limited understanding of the
      specific correlates of protective immunity. Recent monkeypox virus challenge
      studies have established the black-tailed prairie dog (Cynomys ludovicianus) as a
      model of human systemic OPV infections. In this study, we assess the induction of
      humoral immunity in humans and prairie dogs receiving Dryvax, Acam2000, or
      Imvamune vaccine and characterize the proteomic profile of immune recognition
      using enzyme-linked immunosorbent assays (ELISA), neutralization assays, and
      protein microarrays. We confirm anticipated similarities of antigenic protein
      targets of smallpox vaccine-induced responses in humans and prairie dogs and
      identify several differences. Subsequent monkeypox virus intranasal infection of
      vaccinated prairie dogs resulted in a significant boost in humoral immunity
      characterized by a shift in reactivity of increased intensity to a broader range
      of OPV proteins. This work provides evidence of similarities between the vaccine
      responses in prairie dogs and humans that enhance the value of the prairie dog
      model system as an OPV vaccination model and offers novel findings that form a
      framework for examining the humoral immune response induced by systemic
      orthopoxvirus infection.

PMID- 23135729
TI  - Lethal canine distemper virus outbreak in cynomolgus monkeys in Japan in 2008.
AB  - Canine distemper virus (CDV) has recently expanded its host range to nonhuman
      primates. A large CDV outbreak occurred in rhesus monkeys at a breeding farm in
      Guangxi Province, China, in 2006, followed by another outbreak in rhesus monkeys
      at an animal center in Beijing in 2008. In 2008 in Japan, a CDV outbreak also
      occurred in cynomolgus monkeys imported from China. In that outbreak, 46 monkeys
      died from severe pneumonia during a quarantine period. A CDV strain (CYN07-dV)
      was isolated in Vero cells expressing dog signaling lymphocyte activation
      molecule (SLAM). Phylogenic analysis showed that CYN07-dV was closely related to
      the recent CDV outbreaks in China, suggesting continuing chains of CDV infection
      in monkeys. In vitro, CYN07-dV uses macaca SLAM and macaca nectin4 as receptors
      as efficiently as dog SLAM and dog nectin4, respectively. CYN07-dV showed high
      virulence in experimentally infected cynomolgus monkeys and excreted progeny
      viruses in oral fluid and feces. These data revealed that some of the CDV
      strains, like CYN07-dV, have the potential to cause acute systemic infection in
      monkeys.

PMID- 23135730
TI  - Cerebral vasculitis complicating postoperative meningitis: the role of steroids
      revisited.
AB  - Meningitis due to Streptococcus pneumoniae is a rare complication of trans
      sphenoidal surgery. We present the case of a patient who developed pneumococcal
      meningitis with associated bacteraemia after elective endoscopic trans-sphenoidal
      resection of a pituitary macro-adenoma. After initial treatment with ceftriaxone
      and dexamethasone, the patient made a good recovery and dexamethasone was
      discontinued. Two days later the patient's condition deteriorated rapidly,
      presenting focal and diffuse neurological deficits. Cerebral MRI revealed
      widespread punctate ischaemic-type lesions affecting both anterior and posterior
      vascular territories bilaterally and involving features consistent with cerebral
      vasculitis. Antibiotic treatment was broadened to include meropenem and
      dexamethasone was restarted, but the patient remained in a comatose state and
      died 14 days later. Steroid treatment may play a dual role in this poorly
      characterised infectious complication of trans-sphenoidal pituitary surgery. This
      possibility is discussed and the options for prophylaxis are reviewed.

PMID- 23135731
TI  - Regulation of survival and chemoresistance by HSP90AA1 in ovarian cancer SKOV3
      cells.
AB  - Previous researches have showed that HSP90AA is important in ovarian cancer, but
      the mechanism of HSP90AA is still unknown. This study aimed to investigate the
      role of the potential therapy target protein HSP90AA1 in ovarian cancer. The
      level of HSP90AA1 in ovarian cancer SKOV3 cell line was altered by RNAi and
      overexpression. Survival of these cell lines was investigated by tetrazolium
      based assay and fluorescence-activated cell sorter (FACS). The chemosensitivity
      to cisplatin of the cell was also tested by FACS when HSP90AA1 was overexpressed.
      HSP90AA1 RNAi inhibited the proliferation of ovarian cancer SKOV3 cell line and
      increased the apoptosis. Furthermore, overexpression of HSP90AA1 decreased the
      chemosensitivity to cisplatin of SKOV3 cells and overexpression of HSP90AA1 could
      partially rescue the survival rate of SKOV3 cells which were treated with
      cisplatin. HSP90AA1 is required for the survival and proliferation of SKOV3
      cells. High level of HSP90AA1 can increase chemoresistance to cisplatin of SKOV3
      cells.

PMID- 23135733
TI  - [Axillary dissection vs. no axillary dissection in women with invasive breast
      cancer and sentinel node metastasis: implications for the radiation oncologist].

PMID- 23135732
TI  - Prokaryotic expression, purification and functional characterization of
      recombinant human RIP2.
AB  - Receptor-interacting protein 2 (RIP2) is a member of the receptor interacting
      protein (RIP) family and plays an important role in the innate and adaptive
      immune responses. Overexpression of RIP2 mediates divergent signaling pathways
      including NF-kappaB activation and cell death. To further investigate the
      biological activity of RIP2 in vitro, a large amount of purified protein is
      required. For this purpose, the full length of RIP2 was cloned from human Ramos
      (human Burkitt lymphoma) tumor cells and inserted in a prokaryotic expression
      vector pET22b, and then the recombinant plasmid was transformed into E. coli BL21
      (DE3) competent cells. The expression of RIP2 was induced with IPTG. SDS-PAGE
      analysis showed that recombinant human RIP2 (rhRIP2) was mainly expressed as
      soluble fraction in the supernatant of the cell lysate. The recombinant protein
      was subsequently purified by His Trap FF crude to a purity of 90 %. MTT assay of
      the purified rhRIP2 showed its functional diversity in different cell lines, a
      specific inhibitory effect on MCF7 cells, but a promotion on the proliferation of
      Ramos cells. Furthermore, we identified that rhRIP2 could suppress activation of
      canonical NF-kappaB in MCF7 cells and activate non-canonical NF-kappaB signaling
      in Ramos cells, these data suggested that RIP2 participates in different
      signaling pathways contributing to its specific effects in vitro. Our results
      provided new clues to further explore the regulation mechanisms of RIP2 in
      tumorigenesis.

PMID- 23135734
TI  - Efficient solvent system containing malonamides in room temperature ionic
      liquids: actinide extraction, fluorescence and radiolytic degradation studies.
AB  - Solvent extraction studies of actinide metal ions such as Am(III), U(VI), Np(IV),
      Np(VI), Pu(IV) were carried out in a nitric acid medium using two diamides (L)
      viz. (DMDBTDMA (N,N'-dimethyl-N,N'-dibutyl-2-tetradecylmalonamide) and DMDOHEMA
      (N,N'-dimethyl-N,N'-dioctyl-2-(2'-(hexyloxy)ethyl)-malonamide) dissolved in
      different room temperature ionic liquids (RTILs). The use of RTILs as the diluent
      significantly enhanced metal ion extraction as compared to that observed in non
      polar diluent such as n-dodecane. The effects of parameters such as kinetics,
      aqueous phase acidity (0.01-3 M HNO(3)), metal ion oxidation states, diamide
      concentration on the extraction of metal ions were studied. The stoichiometry of
      the extracted Am(III) species using these diamides varied with ligand
      concentration viz. (Am.3L)(3+) ([L] = 0.005-0.02 M) and (Am.2-2.5L)(3+) ([L] =
      0.05-0.1 M). Time resolved laser induced fluorescence spectroscopy (TRLFS)
      studies showed that the extracted species of Eu(III) in an ionic liquid medium
      had no coordinated water molecules, in contrast to the presence of 1-2 water
      molecules in the extracted species in a n-dodecane medium. The radiolytic
      degradation behavior of the diamides/RTIL system has been studied using IR
      spectroscopy and gas chromatography-mass spectrometry (GC-MS). The data revealed
      that a significantly lower ligand concentration is required for actinide
      extraction in ionic liquids as the extraction media as compared to nonpolar
      diluents.

PMID- 23135735
TI  - Virtual liver resection: computer-assisted operation planning using a three
      dimensional liver representation.
AB  - In liver surgery, understanding the complicated liver structures and a detailed
      evaluation of the functional liver remnant volume are essential to perform safe
      surgical procedures. Recent advances in imaging technology have enabled operation
      planning using three-dimensional (3D) image-processing software. Virtual liver
      resection systems provide (1) 3D imaging of liver structures, (2) detailed
      volumetric analyses based on portal perfusion, and (3) quantitative estimates of
      the venous drainage area, enabling the investigation of uncharted fields that
      cannot be examined using a conventional two-dimensional modality. The next step
      in computer-assisted liver surgery is the application of a virtual hepatectomy to
      real-time operations. However, the need for a precise alignment between the
      preoperative imaging data and the intraoperative situation remains to be
      adequately addressed, since the liver is subject to deformation and respiratory
      movements during the surgical procedures. We expect that the practical
      application of a navigation system for transferring the preoperative planning to
      real-time operations could make liver surgery safer and more standardized in the
      near future.

PMID- 23135736
TI  - Intraspecies differences in cold hardiness, carbohydrate content and beta-amylase
      gene expression of Vaccinium corymbosum during cold acclimation and
      deacclimation.
AB  - Changes in cold hardiness, carbohydrate content and beta-amylase gene expression
      were monitored in the shoots of the highbush blueberry (Vaccinium corymbosum L.)
      cultivars 'Sharpblue' and 'Jersey' during cold acclimation (CA) and deacclimation
      (DA). The seasonal patterns were similar in both cultivars, but the levels of
      cold hardiness determined by electrolyte leakage analysis were significantly
      different; 'Jersey' was hardier than 'Sharpblue'. Cold hardiness was closely
      related to total soluble sugar content (r = -0.98** and -0.99** for 'Sharpblue'
      and 'Jersey', respectively). In 'Jersey', more soluble sugars accumulated during
      CA. Of the detected soluble sugars, glucose, fructose and raffinose contents were
      significantly associated with cold hardiness in both cultivars. Sucrose was
      abundant in both cultivars, and stachyose content changed significantly during CA
      and DA. However, they were not associated with cold hardiness. A sharp decrease
      in starch contents in the middle of CA coincided with beta-amylase gene (VcBMY)
      expression, indicating the conversion of starch into soluble sugars. During CA,
      VcBMY was expressed up to twofold higher in 'Jersey' than in 'Sharpblue'. These
      results suggest that intraspecies differences in the cold hardiness of highbush
      blueberries are associated with total soluble sugar content, which is driven
      partly by differential expression of VcBMY.

PMID- 23135737
TI  - A statistical method for estimating wood thermal diffusivity and probe geometry
      using in situ heat response curves from sap flow measurements.
AB  - The heat pulse method is widely used to measure water flux through plants; it
      works by using the speed at which a heat pulse is propagated through the system
      to infer the velocity of water through a porous medium. No systematic, non
      destructive calibration procedure exists to determine the site-specific
      parameters necessary for calculating sap velocity, e.g., wood thermal diffusivity
      and probe spacing. Such parameter calibration is crucial to obtain the correct
      transpiration flux density from the sap flow measurements at the plant scale and
      subsequently to upscale tree-level water fluxes to canopy and landscape scales.
      The purpose of this study is to present a statistical framework for sampling and
      simultaneously estimating the tree's thermal diffusivity and probe spacing from
      in situ heat response curves collected by the implanted probes of a heat ratio
      measurement device. Conditioned on the time traces of wood temperature following
      a heat pulse, the parameters are inferred using a Bayesian inversion technique,
      based on the Markov chain Monte Carlo sampling method. The primary advantage of
      the proposed methodology is that it does not require knowledge of probe spacing
      or any further intrusive sampling of sapwood. The Bayesian framework also enables
      direct quantification of uncertainty in estimated sap flow velocity. Experiments
      using synthetic data show that repeated tests using the same apparatus are
      essential for obtaining reliable and accurate solutions. When applied to field
      conditions, these tests can be obtained in different seasons and can be automated
      using the existing data logging system. Empirical factors are introduced to
      account for the influence of non-ideal probe geometry on the estimation of heat
      pulse velocity, and are estimated in this study as well. The proposed methodology
      may be tested for its applicability to realistic field conditions, with an
      ultimate goal of calibrating heat ratio sap flow systems in practical
      applications.

PMID- 23135738
TI  - Seasonal variation of heartwood formation in Larix kaempferi.
AB  - Heartwood in tree stems provides natural durability and ornamental values to wood
      products as well as antimicrobial properties to protect living stems from decay.
      Control of the amount and quality of heartwood is required because of its
      importance in wood utilization. Despite the importance, the mechanism of
      heartwood formation has been poorly understood. To obtain further knowledge for
      understanding this mechanism, we studied the seasonal variation of various
      components of heartwood formation in Larix kaempferi (Lamb.) Carriere.
      Dehydration of tracheids at the boundary between sapwood and intermediate wood
      occurred continuously during the study period. The death of ray parenchyma cells
      at intermediate wood occurred from spring to summer. The deposition of heartwood
      substance took place in autumn to winter. Thus, different components of heartwood
      formation were active in different seasons. Since heartwood formation is a system
      consisting of several components within a series of continuing processes,
      understanding the seasonal change of heartwood formation requires monitoring
      these components simultaneously.

PMID- 23135739
TI  - Growth phenology of coast Douglas-fir seed sources planted in diverse
      environments.
AB  - The timing of periodic life cycle events in plants (phenology) is an important
      factor determining how species and populations will react to climate change. We
      evaluated annual patterns of basal-area and height growth of coast Douglas-fir
      (Pseudotusga menziesii var. menziesii (Mirb.) Franco) seedlings from four seed
      sources that were planted in four diverse environments as part of the Douglas-fir
      Seed-Source Movement Trial. Stem diameters and heights were measured periodically
      during the 2010 growing season on 16 open-pollinated families at each study
      installation. Stem diameters were measured on a subset of trees with electronic
      dendrometers during the 2010 and 2011 growing seasons. Trees from the four seed
      sources differed in phenology metrics that described the timing of basal-area and
      height-growth initiation, growth cessation and growth rates. Differences in the
      height-growth metrics were generally larger than differences in the basal-area
      growth metrics and differences among installations were larger than differences
      among seed sources, highlighting the importance of environmental signals on
      growth phenology. Variations in the height- and basal-area growth metrics were
      correlated with different aspects of the seed-source environments: precipitation
      in the case of height growth and minimum temperature in the case of basal-area
      growth. The detailed dendrometer measurements revealed differences in growth
      patterns between seed sources during distinct periods in the growing season. Our
      results indicate that multiple aspects of growth phenology should be considered
      along with other traits when evaluating adaptation of populations to future
      climates.

PMID- 23135740
TI  - Growth enhancement of Picea abies trees under long-term, low-dose N addition is
      due to morphological more than to physiological changes.
AB  - Human activities have drastically increased nitrogen (N) inputs into natural and
      near-natural terrestrial ecosystems such that critical loads are now being
      exceeded in many regions of the world. This implies that these ecosystems are
      shifting from natural N limitation to eutrophication or even N saturation. This
      process is expected to modify the growth of forests and thus, along with
      management, to affect their carbon (C) sequestration. However, knowledge of the
      physiological mechanisms underlying tree response to N inputs, especially in the
      long term, is still lacking. In this study, we used tree-ring patterns and a dual
      stable isotope approach (delta(13)C and delta(18)O) to investigate tree growth
      responses and the underlying physiological reactions in a long-term, low-dose N
      addition experiment (+23 kg N ha(-1) a(-1)). This experiment has been conducted
      for 14 years in a mountain Picea abies (L.) Karst. forest in Alptal, Switzerland,
      using a paired-catchment design. Tree stem C sequestration increased by ~22%,
      with an N use efficiency (NUE) of ca. 8 kg additional C in tree stems per kg of N
      added. Neither earlywood nor latewood delta(13)C values changed significantly
      compared with the control, indicating that the intrinsic water use efficiency
      (WUE(i)) (A/g(s)) did not change due to N addition. Further, the isotopic signal
      of delta(18)O in early- and latewood showed no significant response to the
      treatment, indicating that neither stomatal conductance nor leaf-level
      photosynthesis changed significantly. Foliar analyses showed that needle N
      concentration significantly increased in the fourth to seventh treatment year,
      accompanied by increased dry mass and area per needle, and by increased tree
      height growth. Later, N concentration and height growth returned to nearly
      background values, while dry mass and area per needle remained high. Our results
      support the hypothesis that enhanced stem growth caused by N addition is mainly
      due to an increased leaf area index (LAI). Higher LAI implies that more
      photosynthetically active radiation is absorbed and therefore canopy-level
      photosynthesis is increased. We conclude that models assuming that N deposition
      increases tree growth through higher leaf-level photosynthesis may be
      mechanistically inaccurate, at least in forest canopies that are not (yet)
      completely closed.

PMID- 23135741
TI  - Radiation dose study of 64-slice spiral CT coronary angiography: a paired design.
AB  - To compare image noise and radiation dose differences between prospective and
      retrospective ECG-gated computed tomography (CT) coronary artery imaging with 64
      slice spiral CT (64-MSCT) in a paired design. Prospective and retrospective ECG
      gated CT coronary angiography was performed among 20 out-patients with suspected
      coronary artery diseases. If one protocol failed, chose the other instead. The
      differences in effective dose (ED), image noise, contrast-to-noise ratio (CNR)
      and signal-to-noise ratio (SNR) between the two scan protocols were compared.
      Usual causes of failures were analysed for each. The average ED of retrospective
      and prospective protocol was 21.6+/-2 and 6.0+/-1.2 mSv, respectively. There was
      a significant statistical difference in the two protocols (p < 0.05 and 6.16e(
      14)). The image noise and SNR between the two protocols made no differences
      (p=0.71, 0.26, >0.05). The average image noise and SNR of retrospective and
      prospective protocol were (27.95+/-2.82, 28.66+/-2.9) and (12.15+/-1.83, 10.9+/
      1.17). The CNR of retrospective and prospective protocol was (14.52+/-1.59) and
      (17.3+/-2.09), respectively. There was a statistical difference (p < 0.05 and
      0.045). The prospective protocol can lower the ED of 64-MSCT a lot than the
      retrospective protocol. The image noise and SNR made no differences, whereas the
      prospective protocol gave a better CNR result.

PMID- 23135742
TI  - New liquid crystalline materials based on two generations of dendronised
      cyclophosphazenes.
AB  - A divergent approach was used for the synthesis of dendritic structures based on
      a cyclotriphosphazene core with 12 or 24 hydroxyl groups, by starting from
      [N(3)P(3)(OC(6)H(4)OH-4)(6)] and using an acetal-protected 2,2
      di(hydroxymethyl)propionic anhydride as the acylating agent. Hydroxyl groups in
      these first- and second-generation dendrimers, G1-(OH)(12) or G2-(OH)(24), were
      then condensed in turn with mono- or polycatenar pro-mesogenic acids to study
      their ability to promote self-assembly into liquid crystalline structures.
      Reactions were monitored by using (31)P{(1)H} and (1)H NMR spectroscopy and the
      chemical structure of the resulting materials was confirmed by using different
      spectroscopic techniques and mass spectrometry (MALDI-TOF MS). The results were
      in accordance with monodisperse, fully functionalised cyclotriphosphazene
      dendrimers. Thermal and liquid crystalline properties were studied by using
      optical microscopy, differential scanning calorimetry and X-ray diffraction. The
      dendrimer with 12 4-pentylbiphenyl mesogenic units gives rise to columnar
      rectangular organisation, whereas the one with 24 pentylbiphenyl units does not
      exhibit mesomorphic behaviour. In the case of materials that contain polycatenar
      pro-mesogenic units with two aromatic rings (A4 vs. A5), the incorporation of a
      short flexible spacer connected to the periphery of the dendron (acid A5) was
      needed to achieve mesomorphic organisation. In this case, both dendrimer
      generations G1 A5 and G2 A5 exhibit a hexagonal columnar mesophase.

PMID- 23135743
TI  - Segmented flow reactors for nanocrystal synthesis.
AB  - In the past decade microreactors have emerged as a compelling technology for the
      highly controlled synthesis of colloidal nanocrystals, offering multiple
      advantages over conventional batch synthesis methods (including improved levels
      of control, reproducibility, and automation). Initial work in the field employed
      simple continuous phase reactors that manipulate miscible streams of a single
      reagent phase. Recently, however, there has been increasing interest in segmented
      flow reactors that use an immiscible fluid to divide the reagent phase into
      discrete slugs or droplets. Key advantages of segmented flow include the
      elimination of velocity dispersion (a significant cause of polydispersity) and
      greatly reduced susceptibility to reactor fouling. In this progress report we
      review the operation of segmented flow microreactors, their application to the
      controlled synthesis of nanocrystals, and some of the principal challenges that
      must be addressed before they can become a mainstream technology for the
      controlled production of nanomaterials.

PMID- 23135744
TI  - Assessing the impact of osteoporosis on the burden of hip fractures.
AB  - The aim of the study was to determine the number of hip fractures within defined
      countries for 2010 and the proportion attributable to osteoporosis. The number of
      incident hip fractures in one year in countries for which data were available was
      calculated from the population demography in 2010 and the age- and sex-specific
      risk of hip fracture. The number of hip fractures attributed to osteoporosis was
      computed as the number of hip fractures that would be saved assuming that no
      individual could have a femoral neck T-score of less than -2.5 SD (i.e., the
      lowest attainable T-score was that at the threshold of osteoporosis (=-2.5 SD).
      The total number of new hip fractures for 58 countries was 2.32 million (741,005
      in men and 1,578,809 in women) with a female-to-male ratio of 2.13. Of these
      1,159,727 (50 %) would be saved if bone mineral density in individuals with
      osteoporosis were set at a T-score of -2.5 SD. The majority (83 %) of these
      "prevented" hip fractures were found in men and women at the age of 70 years or
      more. The 58 countries assessed accounted for 83.5 % of the world population aged
      50 years or more. Extrapolation to the world population using age- and sex
      specific rates gave an estimated number of hip fractures of approximately 2.7
      million in 2010, of which 1,364,717 were preventable with the avoidance of
      osteoporosis (264,162 in men and 1,100,555 in women). We conclude that
      osteoporosis accounts for approximately half of all hip fractures. Strategies to
      prevent osteoporosis could save up to 50 % of all hip fractures.

PMID- 23135745
TI  - Trees Assembling Mann-Whitney approach for detecting genome-wide joint
      association among low-marginal-effect loci.
AB  - Common complex diseases are likely influenced by the interplay of hundreds, or
      even thousands, of genetic variants. Converging evidence shows that genetic
      variants with low marginal effects (LMEs) play an important role in disease
      development. Despite their potential significance, discovering LME genetic
      variants and assessing their joint association on high-dimensional data (e.g.,
      genome-wide data) remain a great challenge. To facilitate joint association
      analysis among a large ensemble of LME genetic variants, we proposed a
      computationally efficient and powerful approach, which we call Trees Assembling
      Mann-Whitney (TAMW). Through simulation studies and an empirical data
      application, we found that TAMW outperformed multifactor dimensionality reduction
      (MDR) and the likelihood ratio-based Mann-Whitney approach (LRMW) when the
      underlying complex disease involves multiple LME loci and their interactions. For
      instance, in a simulation with 20 interacting LME loci, TAMW attained a higher
      power (power = 0.931) than both MDR (power = 0.599) and LRMW (power = 0.704). In
      an empirical study of 29 known Crohn's disease (CD) loci, TAMW also identified a
      stronger joint association with CD than those detected by MDR and LRMW. Finally,
      we applied TAMW to Wellcome Trust CD GWAS to conduct a genome-wide analysis. The
      analysis of 459K single nucleotide polymorphisms was completed in 40 hrs using
      parallel computing, and revealed a joint association predisposing to CD (P-value
      = 2.763 * 10(-19)). Further analysis of the newly discovered association
      suggested that 13 genes, such as ATG16L1 and LACC1, may play an important role in
      CD pathophysiological and etiological processes.

PMID- 23135746
TI  - Correlated changes in circadian clocks in response to selection for faster pre
      adult development in fruit flies Drosophila melanogaster.
AB  - Although, circadian clocks are believed to be involved in the regulation of life
      history traits such as pre-adult development time and lifespan in fruit flies
      Drosophila melanogaster, there is very little unequivocal evidence either to
      support or refute this. Here we report the results of a long-term study aimed at
      examining the role of circadian clocks in the temporal regulation of pre-adult
      development in D. melanogaster. We employed laboratory selection protocol for
      faster pre-adult development on four large, outbred, random mating populations of
      Drosophila. We assayed pre-adult development time and circadian period of
      locomotor activity rhythm of these flies at regular intervals of 5-10
      generations. After 50 generations of selection, the overall egg-to-adult duration
      in the selected stocks was reduced by ~29 h (~12.5%) relative to controls, with
      the selected populations showing a concurrent reduction in time taken to
      hatching, pupation and wing pigmentation, by ~2, ~16, and ~25.2 h, respectively.
      Furthermore, selected populations showed a concomitant reduction in the circadian
      period of locomotor activity rhythm, implying that circadian clocks and
      development time are correlated. Thus, our study provides the first ever
      unequivocal evidence for the evolution of circadian clocks as a correlated
      response to selection for faster pre-adult development, suggesting that circadian
      clocks and development are linked in fruit flies D. melanogaster.

PMID- 23135747
TI  - Three meta-analyses define a set of commonly overexpressed genes from microarray
      datasets on astrocytomas.
AB  - Glioma is one of the most common tumors of the central nervous system, and one of
      its main types is astrocytoma. Microarray technology has been widely used to
      explore the molecular mechanism of cancer. It is universally accepted that meta
      analysis considerably improves the statistical robustness of results,
      particularly in clinical research. To obtain the maximum reliability, we used
      three different meta-analyses to integrate the four microarray datasets,
      GSE16011, GSE4290, GSE2223, and GSE19728 (local), and defined the common
      differentially expressed genes (DEGs) in astrocytomas compared with normal brain
      tissue. Four DEGs, PCNA, CDC2, CDK2 and CCNB2, which are components of the cell
      cycle pathway, were chosen for Real-Time Polymerase Chain Reaction (RT-PCR) and
      immunohistochemistry validation. PCNA is similar to the P53 gene and has been
      widely implicated in various cancers including gliomas. Therefore, the expression
      status of PCNA in our study was considered as a reference to test our whole
      experimental scheme, and the results indicate that our methodology is valid.
      Although a few studies have reported the overexpression of the CDC2, CDK2 and
      CCNB2 genes in glioma cell lines, we are the first to identify the statuses of
      these genes in human astrocytoma tissues at the mRNA and protein levels. The
      results of the gene validations strongly suggested that the genes play an
      important role in astrocytomas and could potentially be valuable in the diagnosis
      and treatment of astrocytoma.

PMID- 23135748
TI  - When do learners shift from habitual to agenda-based processes when selecting
      items for study?
AB  - Learners presumably attempt to allocate their study time to maximize reward, yet
      in some contexts, their study choices are driven by reading biases that would not
      maximize reward. For instance, when presented with items in a horizontal array
      that are worth different values if correctly recalled, learners will often first
      select the leftmost item (i.e., a reading bias), even when it is associated with
      the lowest value. In four experiments, we investigated the degrees to which
      various factors cause learners to shift to agenda-based regulation. On each
      trial, participants were presented with three cues and a point value (1, 3, or 5)
      for each. The participants could select any cue for study (in which case, its
      target would be presented) in any order. In Experiment 1, participants either
      selected items for study under time pressure or were given unlimited time to
      select items. Not limiting selection time increased the likelihood that higher
      valued items would be prioritized for study, but reading biases still influenced
      item selection. In Experiment 2, participants could select only one item per
      trial, and higher-valued items were prioritized even more for study, but not
      exclusively so. In Experiments 3 and 4, we ruled out a lack of motivation and
      inaccurate task beliefs as explanations for why participants would sometimes
      choose lower-valued items. The results demonstrate the influence of a pervasive
      reading bias on learners' item selections, but as importantly, they show that a
      shift toward agenda use occurs when habitual responding cannot maximize reward.

PMID- 23135749
TI  - Probability matching in risky choice: the interplay of feedback and strategy
      availability.
AB  - Probability matching in sequential decision making is a striking violation of
      rational choice that has been observed in hundreds of experiments. Recent studies
      have demonstrated that matching persists even in described tasks in which all the
      information required for identifying a superior alternative strategy-maximizing
      is present before the first choice is made. These studies have also indicated
      that maximizing increases when (1) the asymmetry in the availability of matching
      and maximizing strategies is reduced and (2) normatively irrelevant outcome
      feedback is provided. In the two experiments reported here, we examined the joint
      influences of these factors, revealing that strategy availability and outcome
      feedback operate on different time courses. Both behavioral and modeling results
      showed that while availability of the maximizing strategy increases the choice of
      maximizing early during the task, feedback appears to act more slowly to erode
      misconceptions about the task and to reinforce optimal responding. The results
      illuminate the interplay between "top-down" identification of choice strategies
      and "bottom-up" discovery of those strategies via feedback.

PMID- 23135750
TI  - HMGA2 elicits EMT by activating the Wnt/beta-catenin pathway in gastric cancer.
AB  - BACKGROUND: The high mobility group protein A2 (HMGA2) is an architectural
      transcription factor that plays an important role in the development and
      progression of many malignant neoplasms. High expression of HMGA2 in gastric
      cancer correlates with invasiveness of cancer and is an independent prognostic
      factor. The reason for this might be HMGA2 promoting epithelial-mesenchymal
      transitions (EMT), which is the key process of metastasis for some underlying
      mechanisms. AIMS: This study was designed to test whether HMGA2 participates in
      the EMT and to further understand the underlying mechanisms of EMT promoted by
      HMGA2. METHODS: We examined the cell biology and molecular biology changes after
      overexpression and knockdown HMGA2 of gastric cancer cells in vitro and vivo. To
      further understand the underlying mechanisms of EMT promoted by HMGA2, based on
      our previous study, we examined the changes of target genes of HMGA2 after
      overexpression and knockdown HMGA2 of gastric cancer cells. RESULTS: The results
      indicated that overexpressing HMGA2 enabled enhancing the oncogenic properties of
      gastric epithelial origin cell in vitro and in vivo. Furthermore, our study
      showed that HMGA2 was able to elicit EMT and regulate several genes which are
      closely related to the Wnt/beta-catenin pathway by directly binding to their
      promoter thereby activating the Wnt/beta-catenin pathway. CONCLUSIONS: The
      Wnt/beta-catenin pathway activated by HMGA2 might be the underlying mechanism of
      EMT in gastric cancer cells.

PMID- 23135751
TI  - Differential effects of estrogen receptor ligands on regulation of
      dihydrotestosterone-induced cell proliferation in endothelial and prostate cancer
      cells.
AB  - Androgen deprivation therapy of prostate cancer with estrogens shows significant
      cardiovascular side-effects. To develop effective prostate cancer therapeutic
      agent(s) with minimal cardiovascular side-effects, we compared the effects of
      various estrogen receptor (ER) ligands on the modulation of dihydrotestosterone
      (DHT) actions in LAPC-4 and LNCaP prostate cancer cells and human aortic
      endothelial cells (HAECs). DHT stimulated the proliferation of HAEC, LAPC-4 and
      LNCaP cells and induced PSA mRNA expression in LAPC-4 cells. These DHT actions
      were differentially modulated by ER ligands in a cell-dependent manner. In LAPC-4
      cells, knockdown of ERbeta expression partially eliminated the betaE2 inhibition
      of DHT-induced LAPC-4 cell proliferation, and a parallel change was observed
      between ER ligand modulation of DHT-induced cell proliferation and cyclin A
      expression. The obtained data suggest that it is feasible to develop effective
      agent(s) for prostate cancer therapy with minimal cardiovascular side-effects and
      17alpha-estradiol and genistein are such potential agents.

PMID- 23135752
TI  - Plant response to lead in the presence or absence EDTA in two sunflower genotypes
      (cultivated H. annuus cv. 1114 and interspecific line H. annuus * H.
      argophyllus).
AB  - The aim of the present work was to study the response of two sunflower genotypes
      (cultivated sunflower Helianthus annuus cv. 1114 and newly developed genotype H.
      annuus * Helianthus argophyllus) to Pb medium-term stress and the role of
      exogenously applied EDTA in alleviating Pb toxicity in hydroponics. Plant growth,
      morpho-anatomical characteristics of the leaf tissues, electrolyte leakage, total
      antioxidant activity, free radical scavenging capacity, total flavonoid content,
      and superoxide dismutase isoenzyme profile were studied by conventional methods.
      Differential responses of both genotypes to Pb supplied in the nutrient solution
      were recorded. Pb treatment induced a decrease in the relative growth rate,
      disturbance of plasma membrane integrity, and changes in the morpho-anatomical
      characteristics of the leaf tissues and in the antioxidant capacity, which were
      more pronounced in the cultivated sunflower H. annuus cv. 1114. The new genotype
      demonstrated higher tolerance to Pb when compared with the cultivar. This was
      mainly due to increased photosynthetically active area, maintenance of plasma
      membrane integrity, permanently high total antioxidant activity, and free radical
      scavenging capacity as well as total flavonoid content. The addition of EDTA into
      the nutrient solution led to limitation of the negative impact of Pb ions on the
      above parameters in both genotypes. This could be related to the reduced content
      of Pb in the roots, stems, and leaves, suggesting that the presence of EDTA
      limited the uptake of Pb. The comparative analysis of the responses to Pb
      treatment showed that the deleterious effect of Pb was more pronounced in the
      cultivated sunflower H. annuus cv. 1114. The new genotype H. annuus * H.
      argophyllus was more productive and demonstrated higher tolerance to Pb medium
      term stress, which could indicate that it may possess certain mechanisms to
      tolerate high Pb concentrations. This character could be inherited from the wild
      parent used in the interspecific hybridization. The ability of EDTA to prevent Pb
      absorption by the plants could underly the mechanism of limiting of the negative
      impact of Pb ions. Hence, EDTA cannot be used to enhance Pb absorption from
      nutrient solution by sunflower plants for phytoremediation purposes.

PMID- 23135753
TI  - Impact of chronic exposure to low doses of chlorpyrifos on the intestinal
      microbiota in the Simulator of the Human Intestinal Microbial Ecosystem (SHIME)
      and in the rat.
AB  - The impact of the insecticide chlorpyrifos (CPF) on the mammalian digestive
      system has been poorly described. The present study aimed at evaluating the
      effect of chronic, low-dose exposure to CPF on the composition of the gut
      microbiota in a Simulator of the Human Intestinal Microbial Ecosystem: the SHIME
      and in rats. The SHIME comprises six reactor vessels (stomach to colon). The
      colonic segments were inoculated with feces from healthy humans. Then, the
      simulator was exposed to a daily dose of 1 mg of CPF for 30 days. The changes
      over time in the populations of bacteria were examined at different time points:
      prior to pesticide exposure (as a control) and after exposure. In parallel,
      pregnant rats were gavaged daily with 1 mg/kg of CPF (or vehicle) until the pups
      were weaned. Next, the rats were gavaged with same dose of CPF until 60 days of
      age (adulthood). Then, samples of different parts of the digestive tract were
      collected under sterile conditions for microbiological assessment. Chronic, low
      dose exposure to CPF in the SHIME and in the rat was found to induce dysbiosis in
      the microbial community with, in particular, proliferation of subpopulations of
      some strains and a decrease in the numbers of others bacteria. In compliance with
      European guidelines, the use of the SHIME in vitro tool would help to (1)
      elucidate the final health effect of toxic agents and (2) minimize (though not
      fully replace) animal testing. Indeed, certain parameters would still have to be
      studied further in vivo.

PMID- 23135754
TI  - Polar organic chemical integrative sampler (POCIS) uptake rates for 17 polar
      pesticides and degradation products: laboratory calibration.
AB  - Polar organic chemical integrative samplers (POCIS) are useful for monitoring a
      wide range of chemicals, including polar pesticides, in water bodies. However,
      few calibration data are available, which limits the use of these samplers for
      time-weighted average concentration measurements in an aquatic medium. This work
      deals with the laboratory calibration of the pharmaceutical configuration of a
      polar organic chemical integrative sampler (pharm-POCIS) for calculating the
      sampling rates of 17 polar pesticides (1.15 <=  logK(ow) <= 3.71) commonly found
      in water. The experiment, conducted for 21 days in a continuous water flow
      through exposure system, showed an integrative accumulation of all studied
      pesticides for 15 days. Three compounds (metalaxyl, azoxystrobine, and
      terbuthylazine) remained integrative for the 21-day experiment. The sampling
      rates measured ranged from 67.9 to 279 mL day(-1) and increased with the
      hydrophobicity of the pesticides until reaching a plateau where no significant
      variation in sampling rate is observed when increasing the hydrophobicity.

PMID- 23135755
TI  - Synthesis of hybrid carbon nanotubes using Brassica juncea L. application to
      photodegradation of bisphenol A.
AB  - Hyperaccumulators contain tubular cellulose and heavy metals, which can be used
      as the sources of carbon and metals to synthesize nanomaterials. In this paper,
      carbon nanotubes (CNTs), Cu(0.05)Zn(0.95)O nanoparticles, and
      CNTs/Cu(0.05)Zn(0.95)O nanocomposites were synthesized using Brassica juncea L.
      plants, and the ultraviolet (UV)-light-driven photocatalytic degradations of
      bisphenol A (BPA) using them as photocatalysts were studied. It was found that
      the outer diameter of CNTs was around 50 nm and there were a few defects in the
      crystal lattice. The synthesized Cu(0.05)Zn(0.95)O nanocomposites had a diameter
      of around 40 nm. Cu(0.05)Zn(0.95)O nanocomposites have grown on the surface of
      the CNTs and the outer diameter of them was around 100 nm. The synthesized hybrid
      carbon nanotubes using B. juncea could enhance the efficiency of photocatalytic
      degradation on BPA. The complete equilibration time of adsorption/desorption of
      BPA onto the surface of CNTs, Cu(0.05)Zn(0.95)O nanoparticles, and
      CNTs/Cu(0.05)Zn(0.95)O nanocomposites was within 30, 20, and 30 min, and
      approximately 14.9, 8.7, and 17.4 % BPA was adsorbed by them, respectively. The
      combination of UV light irradiation (90 min) with CNTs, Cu(0.05)Zn(0.95)O
      nanoparticles, and CNTs/Cu(0.05)Zn(0.95)O nanocomposites could lead to 48.3,
      75.7, and 92.6 % decomposition yields of BPA, respectively. These findings
      constitute a new insight for synthesizing nanocatalyst by reusing
      hyperaccumulators.

PMID- 23135756
TI  - Skin and soft-tissue infections caused by Aeromonas species.
AB  - This study investigated the clinical characteristics of patients with skin and
      soft-tissue infections (SSTIs) due to Aeromonas species. Patients with SSTIs
      caused by Aeromonas species during the period from January 2009 to December 2011
      were identified from a computerized database of a regional hospital in southern
      Taiwan. The medical records of these patients were retrospectively reviewed. A
      total of 129 patients with SSTIs due to Aeromonas species were identified. A.
      hydrophila (n = 77, 59.7 %) was the most common pathogen, followed by A. veronii
      biovar sobria (n = 22, 17.1 %), A. veronii biovar veronii (n = 20, 15.5 %), A.
      caviae (n = 9, 7.0 %), and A. schubertii (n = 1, 0.8 %). The most common isolates
      obtained from patients with polymicrobial infections were Klebsiella species (n =
      33), followed by Enterococcus spp. (n = 24), Enterobacter spp. (n = 21),
      Escherichia coli (n = 17), Staphylococcus spp. (n = 17), Streptococcus spp. (n =
      17), and Acinetobacter spp. (n = 15). Liver cirrhosis and concomitant bacteremia
      were more common among patients with monomicrobial Aeromonas SSTIs than among
      patients with polymicrobial SSTIs. Nine (7 %) patients required limb amputations.
      The in-hospital mortality rate was 1.6 %. In conclusion, Aeromonas species should
      be considered as important causative pathogens of SSTIs, and most infections are
      polymicrobial. In addition, the clinical presentation differs markedly between
      patients with monomicrobial and those with polymicrobial Aeromonas SSTIs.

PMID- 23135757
TI  - Comparison of different phenotypic assays for the detection of extended-spectrum
      beta-lactamase production by inducible AmpC-producing Gram-negative bacilli.
AB  - Routine detection of extended-spectrum beta-lactamase (ESBL) production by AmpC
      producing Enterobacteriaceae in microbiology laboratories is still a problem. The
      aim of this study was to compare the performance of four different phenotypic
      ESBL confirmation assays within this group of Enterobacteriaceae. A total of 83
      AmpC-inducible Enterobacteriaceae were included in this study (58 clinical
      isolates with presumptive ESBL production and 25 molecularly characterized ESBL
      producing isolates). Each isolate was tested for the presence of an ESBL enzyme
      by four phenotypic ESBL confirmation assays: ESBL Etests and combined double-disk
      synergy tests (CDDST), both on Mueller-Hinton (MH) agar with and without the use
      of cloxacillin, an AmpC inhibitor. Our study showed that performing a CDDST on MH
      agar with cefotaxime as the only indicator cephalosporin is not a reliable way to
      detect ESBL-encoding genes among chromosomal AmpC-producing Enterobacteriaceae
      due to its low sensitivity (52 %). The use of cloxacillin in this CDDST could
      only significantly increase the specificity of the CDDST when used with
      ceftazidime as the indicator [sensitivity (SN), 92 %; specificity (SP), 93 %].
      Regarding ESBL Etest(r) strips, the sensitivity of the cefepime strip (80 %) was
      significantly higher compared to the cefotaxime and ceftazidime strips (16 % and
      32 %, respectively). Adding cloxacillin to the MH agar improved the ESBL
      detection of each of these strips. We recommend the CDDST on MH agar supplemented
      with cloxacillin and ceftazidime or cefepime as the indicator cephalosporin as
      the most cost-efficient strategy to confirm ESBL production in inducible AmpC
      producing Enterobacteriaceae.

PMID- 23135758
TI  - Generic alendronate use among Medicare beneficiaries: are Part D data complete?
AB  - BACKGROUND: Generic alendronate was approved in the United States on February 6,
      2008. Medicare beneficiaries might pay for generic alendronate out-of-pocket
      without having claims submitted, resulting in misclassification of generic
      alendronate use in Medicare data. OBJECTIVES: To estimate the completeness of
      generic alendronate use in 2008 Medicare Part D data; to identify factors
      associated with staying on branded alendronate versus switching to a generic
      product. METHODS: We identified Medicare beneficiaries highly adherent
      (medication possession ratio >=80%) with branded alendronate during 1/1/06-2/6/07
      ("2007 cohort") and during 1/1/07-2/6/08 ("2008 cohort"). The outcome was
      medication status at the end of follow-up (12/31/2007 or 12/31/2008), classified
      as continued branded alendronate, switched to generic alendronate, switched to
      another bisphosphonate or presumed discontinued bisphosphonate therapy. Cox
      regression estimated the hazard ratio (HR) for discontinuation in 2008 compared
      to 2007. Multinomial logistic regression identified factors associated with
      medication status for the 2008 cohort. RESULTS: Among 15,310 subjects using
      branded alendronate in the 2008 cohort, 81% switched to generic alendronate. The
      proportion presumably discontinuing bisphosphonate therapy was 8.9% in 2008
      compared to 7.7% in the 2007 cohort (adjusted HR, 1.15; 95% confidence interval,
      1.05, 1.26). Factors associated with staying on branded alendronate in 2008 were
      higher income, eligibility for a low income subsidy and use of Fosamax(r) plus
      vitamin D. CONCLUSION: Evaluation of Medicare prescription drug data suggests
      that the amount of missing claims for generic alendronate in 2008 was not
      substantial, and misclassification of exposure in studies examining alendronate
      use post-generic product availability should be minimal.

PMID- 23135759
TI  - Healthcare costs of inflammatory bowel disease have shifted from hospitalisation
      and surgery towards anti-TNFalpha therapy: results from the COIN study.
AB  - OBJECTIVE: The introduction of anti tumour necrosis factor-alpha (anti-TNFalpha)
      therapy might impact healthcare expenditures, but there are limited data
      regarding the costs of inflammatory bowel diseases (IBD) following the
      introduction of these drugs. We aimed to assess the healthcare costs and
      productivity losses in a large cohort of IBD patients. DESIGN: Crohn's disease
      (CD) and ulcerative colitis (UC) patients from seven university hospitals and
      seven general hospitals were invited to fill-out a web-based questionnaire. Cost
      items were derived from a 3 month follow-up questionnaire and categorised in
      outpatient clinic, diagnostics, medication, surgery and hospitalisation.
      Productivity losses included sick leave of paid and unpaid work. Costs were
      expressed as mean 3-month costs per patients with a 95% CI obtained using non
      parametric bootstrapping. RESULTS: A total of 1315 CD patients and 937 UC
      patients were included. Healthcare costs were almost three times higher in CD as
      compared with UC, ?1625 (95% CI ?1476 to ?1775) versus ?595 (95% CI ?505 to
      ?685), respectively (p<0.01). Anti-TNFalpha use was the main costs driver,
      accounting for 64% and 31% of the total cost in CD and UC. Hospitalisation and
      surgery together accounted for 19% and <1% of the healthcare costs in CD and 23%
      and 1% in UC, respectively. Productivity losses accounted for 16% and 39% of the
      total costs in CD and UC. CONCLUSIONS: We showed that healthcare costs are mainly
      driven by medication costs, most importantly by anti-TNFalpha therapy.
      Hospitalisation and surgery accounted only for a minor part of the healthcare
      costs.

PMID- 23135760
TI  - Insight into the prebiotic concept: lessons from an exploratory, double blind
      intervention study with inulin-type fructans in obese women.
AB  - OBJECTIVE: To highlight the contribution of the gut microbiota to the modulation
      of host metabolism by dietary inulin-type fructans (ITF prebiotics) in obese
      women. METHODS: A double blind, placebo controlled, intervention study was
      performed with 30 obese women treated with ITF prebiotics (inulin/oligofructose
      50/50 mix; n=15) or placebo (maltodextrin; n=15) for 3 months (16 g/day). Blood,
      faeces and urine sampling, oral glucose tolerance test, homeostasis model
      assessment and impedancemetry were performed before and after treatment. The gut
      microbial composition in faeces was analysed by phylogenetic microarray and qPCR
      analysis of 16S rDNA. Plasma and urine metabolic profiles were analysed by 1H-NMR
      spectroscopy. RESULTS: Treatment with ITF prebiotics, but not the placebo, led to
      an increase in Bifidobacterium and Faecalibacterium prausnitzii; both bacteria
      negatively correlated with serum lipopolysaccharide levels. ITF prebiotics also
      decreased Bacteroides intestinalis, Bacteroides vulgatus and Propionibacterium,
      an effect associated with a slight decrease in fat mass and with plasma lactate
      and phosphatidylcholine levels. No clear treatment clustering could be detected
      for gut microbial analysis or plasma and urine metabolomic profile analyses.
      However, ITF prebiotics led to subtle changes in the gut microbiota that may
      importantly impact on several key metabolites implicated in obesity and/or
      diabetes. CONCLUSIONS: ITF prebiotics selectively changed the gut microbiota
      composition in obese women, leading to modest changes in host metabolism, as
      suggested by the correlation between some bacterial species and metabolic
      endotoxaemia or metabolomic signatures.

PMID- 23135761
TI  - Transcriptional analysis of the intestinal mucosa of patients with ulcerative
      colitis in remission reveals lasting epithelial cell alterations.
AB  - OBJECTIVE: Ulcerative colitis (UC) is a chronic condition characterised by the
      relapsing inflammation despite previous endoscopic and histological healing. Our
      objective was to identify the molecular signature associated with UC remission.
      DESIGN: We performed whole-genome transcriptional analysis of colonic biopsies
      from patients with histologically active and inactive UC, and non-inflammatory
      bowel disease (non-IBD) controls. Real-time reverse transcriptase-PCR and
      immunostaining were used for validating selected genes in independent cohorts of
      patients. RESULTS: Microarray analysis (n=43) demonstrates that UC patients in
      remission present an intestinal transcriptional signature that significantly
      differs from that of non-IBD controls and active patients. Fifty-four selected
      genes were validated in an independent cohort of patients (n=30). Twenty-nine of
      these genes were significantly regulated in UC-in-remission subjects compared
      with non-IBD controls, including a large number of epithelial cell-expressed
      genes such as REG4, S100P, SERPINB5, SLC16A1, DEFB1, AQP3 and AQP8, which
      modulate epithelial cell growth, sensitivity to apoptosis and immune function.
      Expression of inflammation-related genes such as REG1A and IL8 returned to
      control levels during remission. REG4, S100P, SERPINB5 and REG1A protein
      expression was confirmed by immunohistochemistry (n=23). CONCLUSIONS: Analysis of
      the gene signature associated with remission allowed us to unravel pathways
      permanently deregulated in UC despite histological recovery. Given the strong
      link between the regulation of some of these genes and the growth and
      dissemination of gastrointestinal cancers, we believe their aberrant expression
      in UC may provide a mechanism for epithelial hyper-proliferation and, in the
      context of malignant transformation, for tumour growth.

PMID- 23135762
TI  - Hepatitis C virus kinetics by administration of pegylated interferon-alpha in
      human and chimeric mice carrying human hepatocytes with variants of the IL28B
      gene.
AB  - OBJECTIVE: Recent studies have demonstrated that genetic polymorphisms near the
      IL28B gene are associated with the clinical outcome of pegylated interferon alpha
      (peg-IFN-alpha) plus ribavirin therapy for patients with chronic hepatitis C
      virus (HCV). However, it is unclear whether genetic variations near the IL28B
      gene influence hepatic interferon (IFN)-stimulated gene (ISG) induction or
      cellular immune responses, lead to the viral reduction during IFN treatment.
      DESIGN: Changes in HCV-RNA levels before therapy, at day 1 and weeks 1, 2, 4, 8
      and 12 after administering peg-IFN-alpha plus ribavirin were measured in 54
      patients infected with HCV genotype 1. Furthermore, we prepared four lines of
      chimeric mice having four different lots of human hepatocytes containing various
      single nucleotide polymorphisms (SNP) around the IL28B gene. HCV infecting
      chimeric mice were subcutaneously administered with peg-IFN-alpha for 2 weeks.
      RESULTS: There were significant differences in the reduction of HCV-RNA levels
      after peg-IFN-alpha plus ribavirin therapy based on the IL28B SNP rs8099917
      between TT (favourable) and TG/GG (unfavourable) genotypes in patients; the first
      phase viral decline slope per day and second-phase slope per week in TT genotype
      were significantly higher than in TG/GG genotype. On peg-IFN-alpha administration
      to chimeric mice, however, no significant difference in the median reduction of
      HCV-RNA levels and the induction of antiviral ISG was observed between favourable
      and unfavourable human hepatocyte genotypes. CONCLUSIONS: As chimeric mice have
      the characteristic of immunodeficiency, the response to peg-IFN-alpha associated
      with the variation in IL28B alleles in chronic HCV patients would be composed of
      the intact immune system.

PMID- 23135764
TI  - Identification of novel missense CTRC variants in Japanese patients with chronic
      pancreatitis.

PMID- 23135765
TI  - Impact of intraoperative MRI-guided transsphenoidal surgery on endocrine function
      and hormone substitution therapy in patients with pituitary adenoma.
AB  - BACKGROUND: Pituitary adenomas are rare with an incidence of 0.4-8.2 per 105
      inhabitants. Symptoms range from headaches to pituitary insufficiency or
      excessive output of hormones with associated disease. Except for prolactinomas,
      surgery is recommended as the first line and most effective treatment for the
      majority of these tumours. One of the refinements of surgical therapy introduced
      was intraoperative magnetic resonance imaging (iMRI). OBJECTIVE: The aim of this
      study was to analyse the postoperative pituitary function and the general outcome
      of patients treated for non-functioning and GH-producing pituitary adenomas with
      a transsphenoidal iMRI-assisted approach using the PoleStarTM N20 imager.
      METHODS: A total of 148 consecutive iMRI-guided surgeries for GH-producing and
      non-functioning pituitary adenomas were retrospectively analysed. Patients'
      clinical data, endocrinological parameters, clinical examinations and pre-/post-
      and intraoperative imaging studies were evaluated. RESULTS: A total of 101
      patients could be classified as being in remission at follow-up; 26 (17.6%) of
      them due to iMRI allowing additional tumour removal. A total of 44 patients
      (29.7%) had more complete tumour removal because remnants were detected by iMRI.
      The mean hormone levels of patients did not differ significantly between pre- and
      postoperative examinations. There were 62 patients with preoperative, and 43
      patients with postoperative pituitary insufficiency, thus, due to surgery there
      were 19 (12.8%) patients with improved pituitary function. CONCLUSIONS: The
      results show this method to be a safe and effective treatment option increasing
      remission rate and keeping complication rate low. Postoperative pituitary
      function was preserved or improved - possibly due to more exact iMRI-assisted
      tumour removal.

PMID- 23135763
TI  - International Cancer of the Pancreas Screening (CAPS) Consortium summit on the
      management of patients with increased risk for familial pancreatic cancer.
AB  - BACKGROUND: Screening individuals at increased risk for pancreatic cancer (PC)
      detects early, potentially curable, pancreatic neoplasia. OBJECTIVE: To develop
      consortium statements on screening, surveillance and management of high-risk
      individuals with an inherited predisposition to PC. METHODS: A 49-expert
      multidisciplinary international consortium met to discuss pancreatic screening
      and vote on statements. Consensus was considered reached if >= 75% agreed or
      disagreed. RESULTS: There was excellent agreement that, to be successful, a
      screening programme should detect and treat T1N0M0 margin-negative PC and high
      grade dysplastic precursor lesions (pancreatic intraepithelial neoplasia and
      intraductal papillary mucinous neoplasm). It was agreed that the following were
      candidates for screening: first-degree relatives (FDRs) of patients with PC from
      a familial PC kindred with at least two affected FDRs; patients with Peutz
      Jeghers syndrome; and p16, BRCA2 and hereditary non-polyposis colorectal cancer
      (HNPCC) mutation carriers with >= 1 affected FDR. Consensus was not reached for
      the age to initiate screening or stop surveillance. It was agreed that initial
      screening should include endoscopic ultrasonography (EUS) and/or MRI/magnetic
      resonance cholangiopancreatography not CT or endoscopic retrograde
      cholangiopancreatography. There was no consensus on the need for EUS fine-needle
      aspiration to evaluate cysts. There was disagreement on optimal screening
      modalities and intervals for follow-up imaging. When surgery is recommended it
      should be performed at a high-volume centre. There was great disagreement as to
      which screening abnormalities were of sufficient concern to for surgery to be
      recommended. CONCLUSIONS: Screening is recommended for high-risk individuals, but
      more evidence is needed, particularly for how to manage patients with detected
      lesions. Screening and subsequent management should take place at high-volume
      centres with multidisciplinary teams, preferably within research protocols.

PMID- 23135766
TI  - Subgel phase structure in monolayers of glycosylphosphatidylinositol glycolipids.

PMID- 23135767
TI  - Changes in bimanual coordination during the first 6 weeks after moderate
      hemiparetic stroke.
AB  - BACKGROUND: Better understanding of how bimanual coordination changes over the
      first weeks of recovery after stroke is required to address the potential utility
      for bimanual rehabilitation. Three-dimensional kinematic analysis can provide
      quantitative assessment of unimanual and bimanual movements. OBJECTIVE: To assess
      the natural evolution of reaching kinematics during standard poststroke
      rehabilitation, focusing on bimanual coordination. METHODS: A total of 12
      hemiparetic, moderately impaired patients were included within 30 days after a
      first unilateral ischemic/hemorrhagic stroke; 7 kinematic assessments were
      performed once a week for 6 weeks and at 3 months after inclusion. The reach-to
      grasp task was performed in 3 different conditions: unimanual with the healthy
      limb (UN), unimanual with the paretic limb (UP), and bimanual (BN/BP). RESULTS:
      For the paretic limb, movement fluency (number of movement units and total
      movement time) was lower for bimanual reaching compared with unimanual reaching.
      For bimanual reaching, (1) movement kinematics were similar for both limbs, (2)
      recovery patterns of both limbs followed a similar profile with a plateau phase
      at 6 weeks poststroke, and (3) intertrial variability of between-hands
      synchronization decreased over sessions, although the mean delays remained the
      same. CONCLUSIONS: Bimanual coordination started to become efficient 6 weeks
      after onset of stroke, so for patients such as those we tested, this time could
      be most opportune to start bimanual-oriented rehabilitation. The challenge in
      future research includes determining the characteristics of patients who may best
      benefit from bimanual therapy.

PMID- 23135768
TI  - Moral concerns with sedation at the end of life.

PMID- 23135769
TI  - [Successful use of C1 esterase inhibitor in capillary leak syndrome].
AB  - This article reports the successful use of C1 esterase inhibitor in the treatment
      of capillary leak syndrome. The coincidence of exposure to latex during surgery
      and medication with ramipril led to prolonged shock complicated by secondary
      hyperfibrinolysis, capillary leak syndrome and multiple organ failure. Initial
      treatment according to relevant guidelines failed to stabilize the condition.
      Treatment was only successful after administration of 1,500 IU of human C1
      esterase inhibitor.

PMID- 23135770
TI  - [Suicide in medical students: case series].
AB  - BACKGROUND: Suicide rates of male and female physicians are about 3-5 times
      higher compared with the general public. Detailed studies about medical student
      suicides in the United States exist but similar current data from German speaking
      countries are lacking. METHODS: In this study suicide among medical students in
      Germany, Austria and Switzerland was analyzed using Medline and Google search
      engines and information from insurance companies, public institutions,
      statistical agencies and leading scientists in Germany, Austria and Switzerland
      was requested. The incidence of suicide among medical students at the Medical
      University of Innsbruck was also examined. RESULTS: In publications from German
      speaking countries some medical student suicides are mentioned but current
      statistics were not available. Between 2006 and 2011 the Tyrolean State Police in
      Austria registered 14 suicides by students of all disciplines. At Innsbruck
      Medical University (approximately 2,800 medical students) it was  found that 6
      medical students committed suicide between June 2007 and June 2012 (rate 36 per
      100,000). CONCLUSIONS: The suicide risk of medical students at the Medical
      University of Innsbruck appears to be increased. Because of a lack of comparable
      data it is not possible to show whether these observations can be extrapolated to
      other universities. It appears that there was no single special event which
      triggered suicide by the medical students but a combination of individual risk
      factors and the environment was involved. However, this problem receives
      insufficient attention.

PMID- 23135771
TI  - [Process optimization by central control of acute pain therapy: implementation of
      standardized treatment concepts and central pain management in hospitals].
AB  - BACKGROUND: The aim of this investigation was to describe the effects of
      standardization and central control of the processes involved in postoperative
      pain management from patient and employee perspectives. MATERIALS AND METHODS:
      Patients (n = 282/307) and respective hospital staff (n = 149/119) evaluated the
      processes, the quality of postoperative pain management and result parameters 3
      months before and 12 months after the introduction of standardization of the
      postoperative pain therapy process using a set of standardized questionnaires.
      RESULTS: Pain level and the waiting period for an analgesic partially decreased
      and a higher subjective effectiveness of medication was achieved in patients
      after the standardization. Patients felt that the pain was taken more seriously
      and contacted the staff for additional medication more frequently. From an
      employee viewpoint the quality of care and individual competence and ability to
      treat pain increased after the introduction of standardization. Pain assessment
      was improved and employees rated their knowledge and education level as higher
      than before the intervention. Patients with pre-existing chronic pain and
      patients with special regional therapy benefited only partially after the
      introduction and an increase in pain intensity was even observed. CONCLUSIONS:
      The quality of care was improved by standardization of the postoperative pain
      management. The legal and practical ability of the nursing stuff to administer
      pain medication within well-defined margins reduced the dependence on the ward
      doctor and at the same time patient pain levels. Patients received analgesics
      more quickly and experienced increased effectiveness. These results should be an
      incentive to reconsider the importance of the organization of postoperative pain
      management, because the quality of care with all potential medical and economic
      advantages, can be easily optimized by such simple mechanisms. They also show
      that the quality assessment of acute pain and the selection of appropriate
      indicators need further development.

PMID- 23135772
TI  - [Tools for drug dosing in life-threatening pediatric emergencies].
AB  - Life-threatening pediatric emergencies are rare events in which precise, correct
      and fast drug dosing is essential. Intravenous drugs are most commonly dosed
      based on the child's weight in mg/kg. Numerous tools exist for aiding the
      physician in the error prone calculation, none of which meet all criteria for the
      perfect tool. Besides frequent training of practical skills and awareness of the
      problem of calculating the exact drug dose, it seems indispensable to have a
      localized tool at hand for these critical events.

PMID- 23135773
TI  - [A new working shift model for anesthesiologists: an analysis 3 years after
      implementation].
AB  - OBJECTIVE: The aim of this study was to assess the efficacy, appropriateness and
      cost-effectiveness of a new working shift model for anesthesiologists complying
      with the European working time directive (EWTD) at the University Hospital of
      Tubingen (UKT), Germany 3 years after implementation BACKGROUND: Applying the
      standards of the EWTD is challenging for university hospitals as doctors must
      comply with the challenge of combining patient care, research and teaching. So
      far there have been no data available for German university hospitals on how
      these requirements can be met. As the department of anesthesiology is also a
      service-providing department it is essential not to increase staffing costs with
      a new shift model. METHODS: In 2007 a new working shift model for the department
      of anesthesiology was designed and introduced in 2008. Shift planning and
      documentation of working hours were implemented electronically. The calculated
      number of doctors to run this model was 87.6 full time equivalents (FTE). For
      2009 and 2010 the compliance with the EWTD parameters was checked for 1) average
      weekly working time limit (AWWTL) and 2) compliance to the maximum daily working
      time limit of 10 h (10 h DWTL). Furthermore, staffing costs for doctors in 2010
      were compared to 2007. To check for the time spent in patient care the period of
      anesthetic attendance (PAA) was chosen, i.e. the total time of patient contact by
      anesthesiology staff. Data were analyzed descriptively for AWWTL and for 10 h
      DWTL. FTE, staff costs and PAA were evaluated by one-way ANOVA. RESULTS: The new
      shift model allowed 84.4 % of all doctors to comply with the individual AWWT
      limits of 54 h and 48 h in 2009 (81/96) and 76.0 % in 2010 (79/104). In 2009 61.5
      % of anesthesiologists voted for opt-out (59/96) and 53.8 % did so in 2010
      (56/104). The 10 h DWTL was respected by 84.0 % in 2009 and by 85.9 % in 2010.
      The mean number of anesthesiologists rose significantly from 78.4 FTE in 2007 to
      82.5 FTE in 2009 and 84.6 FTE in 2010 (p < 0.001 for 2010 vs. 2007, p = 0.004 for
      2009 vs. 2007 and was not significant for 2010 vs. 2009). Staff costs per FTE
      increased from 7,524.79 <euro>/month to 7,800.66 <euro>/month and 7,966.11
      <euro>/month in 2007, 2009 and 2010, respectively with the differences being non
      significant. The PAA increased significantly from a mean of 6,124 h/month in 2007
      to 6,581 h/month in 2009 and 6,872 h/month in 2010 (p < 0.001 for 2010 vs. 2007,
      whereas 2009 vs. 2007 and 2010 vs. 2009 were not significant). Thus, labour costs
      increased from 96.59 <euro>/h PAA in 2007 to 98.53 <euro>/h in both 2009 and
      2010, the differences being not significant. CONCLUSIONS: The newly designed
      shift model allowed a fair compliance with the EWTD in respect to AWTL and 10 h
      DWTL, although the calculated number of doctors to run the shift model could not
      be met in 2009 and 2010. Violations of the 10 h DWT limits were stable in 2009
      and 2010; however the number of doctors exceeding the AWWT limits appeared to
      increase. The compliance with opt-out decreased from 2009 to 2010 and a high
      proportion of AWWTL violations resulted from the group of non-opt-out voters. The
      staff costs per hour PAA after implementation of the new shift model did not
      differ significantly from the year before although staffing costs increased by
      7.2 % between 2007 and 2010. Costs increased by 162,454 <euro>/year for all PAA
      hours in 2010. Further evaluation of staff satisfaction with the new shift models
      is needed and already under way.

PMID- 23135774
TI  - Tramadol and levobupivacaine wound infiltration at cesarean delivery for
      postoperative analgesia.
AB  - PURPOSE: The aim of the present study was to investigate whether levobupivacaine
      and tramadol wound infiltration decreases postoperative pain following Cesarean
      section and reduces the need for analgesics in the immediate post-delivery
      period. METHODS: Ninety patients (aged 18-40 years) scheduled for elective
      Cesarean section under general anesthesia were randomly allocated to one of the
      three groups: the placebo group (group P) received 20 mL local wound infiltration
      with 0.9 % saline solution; the levobupivacaine group (group L) received 20 mL
      local wound infiltration with levobupivacaine 0.25 %; and the tramadol group
      (group T) received 20 mL local wound infiltration with 1.5 mg/kg tramadol within
      0.9 % saline solution. Following the closure of the uterine incision and the
      rectus fascia, 20 mL solution was infiltrated subcutaneously along the skin wound
      edges. The primary outcome was 24-h tramadol consumption. Secondary outcomes were
      recorded VAS scores, diclofenac requirement, fever, vomiting, and wound
      infection. RESULTS: At 15 min postoperatively, VAS values were lower in groups T
      and L than group P (P = 0.0001). The mean 24-h tramadol consumption was lowest in
      group T (P = 0.0001) and it was lower in the group L compared to group P (P =
      0.007) (401.6, 483.3, and 557.5 mg for T, L, and P groups, respectively). There
      was no difference among groups regarding the need for supplemental analgesia
      (rescue diclofenac doses) (P > 0.05). CONCLUSIONS: We conclude that wound
      infiltration with tramadol and levobupivacaine in patients having Cesarean
      section under general anesthesia may be a good choice for postoperative
      analgesia.

PMID- 23135775
TI  - Role of platelet derived growth factor receptor (PDGFR) over-expression and
      angiogenesis in ependymoma.
AB  - New molecularly targeted therapies are needed for childhood ependymoma.
      Angiogenesis and the PDGFR pathway could be potential therapeutic targets. This
      study aimed to screen ependymomas for the expression and clinicopathological
      correlates of angiogenic factors and potential therapeutic targets including
      VEGFR, endoglin (CD105), CD34, CD31, c-Kit, PDGFR-alpha and PDGFR-beta.
      Immunohistochemistry for angiogenesis factors and PDGFR-alpha and beta was
      performed in 24 archival tumor samples from children and adults treated for
      ependymoma at our institution. CD31 density, CD105 density and pericyte coverage
      index (PCI) were calculated. These findings were correlated with clinical
      outcome. VEGFR2 was overexpressed in tumor cells in only one out of 24 cases, but
      was found overexpressed in the vessels in 6 cases. PDGFR-alpha and beta were
      found to be over-expressed in the ependymoma tumor cells in seven out of 24 cases
      (29.2 %). CD31 density, CD105 density and PCI did not correlate with expression
      of PDGFRs. Overexpression of PDGFR-alpha and beta in tumor cells and
      overexpression of PDGFR-alpha in tumor endothelium had prognostic significance
      and this was maintained in multivariate analysis for overexpression of PDGFR
      alpha in tumor cells (2 year progression free survival was 16.7 +/- 15.2 for
      cases with overexpression of PDGFR-alpha in the tumor vs. 74.5 +/- 15.2 for those
      with low/no expression, hazard ratio = 5.78, p = 0.04). A number of angiogenic
      factors are expressed in ependymoma tumor cells and tumor endothelium.
      Preliminary evidence suggests that the expression of PDGFRs could have a
      prognostic significance in ependymoma. This data suggests that PDGFRs should be
      further evaluated as targets using novel PDGFR inhibitors.

PMID- 23135776
TI  - 1H, 13C, 15N resonance assignments of murine hepatitis virus nonstructural
      protein 3a.
AB  - Nonstructural protein (nsp) 3 is the largest of 16 nsps translated from the
      murine hepatitis virus (MHV) genome. The N-terminal most domain of nsp3, nsp3a,
      has been identified by reverse genetics as a likely binding partner of MHV
      nucleocapsid protein. Here we report the backbone and side chain resonance
      assignments of MHV nsp3a (residues 1-114). 

PMID- 23135777
TI  - Shunt survival rates by using the adjustable differential pressure valve combined
      with a gravitational unit (proGAV) in pediatric neurosurgery.
AB  - OBJECT: Overdrainage is a chronic complication in shunted pediatric patients with
      hydrocephalus. The use of adjustability of differential pressure (DP) valves in
      combination with antisiphoning devices may help to overcome this sequela and may
      diminish the rate of possible shunt failures. The purpose of this retrospective
      study is to report our experience on shunt survival and infection rate with an
      adjustable DP valve with integrated gravitational unit in pediatric
      hydrocephalus. METHODS: The proGAV consists of an adjustable differential
      pressure (DP) valve and a gravitational unit. During the time period of July 2004
      and December 2009, a total of 237 adjustable gravitational valves were used in
      203 children (age, 6.5 +/- 6.54; 0-27 years). In the follow-up period, valve and
      shunt failures as well as rate of infection were recorded. RESULTS: Within the
      average follow-up time of 21.9 +/- 10.3 months (range, 6-72 months), the valve
      survival rate was 83.8 %. The overall shunt survival rate including all necessary
      revisions was 64.3 %. Looking at the group of infants (<1 year of age) within the
      cohort, the valve survival rate was 77.3 % and the shunt survival rate was 60.9
      %. The overall infection rate was 4.6 %. CONCLUSION: In a concept of avoiding
      chronic overdrainage by using the proGAV in hydrocephalic children, we observed a
      good rate of valve and shunt survival. Compared to previous reported series, we
      experienced the proGAV as a reliable tool for the treatment of pediatric
      hydrocephalus.

PMID- 23135778
TI  - Phase Ib trial of the oral angiogenesis inhibitor pazopanib administered
      concurrently with erlotinib.
AB  - INTRODUCTION: As angiogenic pathways have become important targets for inhibition
      of tumor growth, we examined the concept of dual pathway blockade by small
      molecule tyrosine kinase inhibitors targeting vascular endothelial and epidermal
      growth factor receptors. METHODS: Escalating doses of pazopanib (400-800 mg once
      daily [QD]) plus erlotinib (100-150 mg QD) doses were evaluated in cohorts of 3-6
      adults with advanced solid tumors. Twelve additional patients were enrolled in an
      expansion cohort to confirm the maximum tolerated dose (MTD). RESULTS: The MTD,
      defined during assessment of 20 patients, was pazopanib 600 mg plus erlotinib 150
      mg. Two dose-limiting toxicities, rash and elevated liver enzymes, occurred at
      pazopanib 800 mg and erlotinib 150 mg. Overall, 30 % and 27 % of patients
      required dose interruption of pazopanib or erlotinib, respectively; 15 % of
      patients required a dose reduction of erlotinib to manage toxicities. The most
      common adverse events in patients treated with any dose regimen of pazopanib plus
      erlotinib (N = 33) were diarrhea, rash, nausea, and decreased appetite. The
      adverse-event profile of the combination did not appear to differ from that of
      each compound administered alone. Coadministration of pazopanib 600 mg QD and
      erlotinib 150 mg QD did not consistently affect the pharmacokinetics of either
      compound relative to that observed for either compound administered alone. Of 26
      patients evaluated for efficacy, 3 (12 %; all non-small-cell lung cancer) had
      partial response and 10 (38 %) had stable disease. CONCLUSIONS: Concomitant
      administration of pazopanib 600 mg and erlotinib 150 mg is feasible, with a
      manageable toxicity profile. These results support further clinical development
      of the pazopanib-erlotinib combination.

PMID- 23135779
TI  - Determinants of patient screen failures in Phase 1 clinical trials.
AB  - OBJECTIVE: Certain eligibility criteria for Phase 1 cancer clinical trials may
      impede successful patient enrollment onto a study. We evaluated patient-specific
      or study-specific reasons for screen failures on Phase 1 oncology clinical trials
      and discuss factors which may inhibit subject enrollment. METHODS: Thirty-eight
      Phase 1 clinical trials for solid tumors meeting eligibility criteria and opened
      for enrollment between February 2006 and February 2011 at one oncology Phase 1
      program were examined. Categorical reasons for screen failures and patients'
      demographics were examined and compared to characteristics of patients that
      successfully enrolled on a Phase 1 trial. RESULTS: There were a total of 583
      successful Phase 1 enrollment and dose administration events out of 773 Phase 1
      consent events (75.4 % dose success rate). The three most common reasons for
      screen failure were: out of protocol-specified range for chemistry, development
      of an interval medical issue that precluded proceeding with study participation,
      and subject declining participation after signing consent. Living further away
      from the Phase 1 program and receipt of fewer prior lines of systemic
      chemotherapy were significantly associated with increased screen failures.
      CONCLUSION: Screen failures for Phase 1 studies are not uncommon (24.6 %). When a
      protocol required tumor or host analyte is not required, most screen failures are
      due to out of protocol-specified range for chemistry or the development of an
      interval medical issue. Screen failure rates were increased when patients had
      longer travel distances and fewer prior lines of systemic chemotherapy.

PMID- 23135780
TI  - Evaluation of the retinal changes in patients with chronic migraine.
AB  - The aim of this study was to investigate retinal nerve fiber layer (RNFL)
      thickness and macular changes (central subfield thickness, cube average
      thickness, cube volume) in patients with chronic migraine (CM) without visual
      impairment using spectral-domain optical coherence tomography (SD-OCT) and to
      compare the results to healthy controls. A total of 80 subjects, including 40 CM
      patients (24 females, 16 males, [corrected] at 19-36 years of age) with no
      migraine prophylactic treatment and 40 healthy controls (22 females, 18 males,
      [corrected] at 20-40 years of age) were enrolled. Both eyes of patients with CM
      and controls were imaged using Cirrus HD SD-OCT (Carl Zeiss Meditec, Dublin, CA,
      USA). The average RNFL thickness was not significantly thinner in patients with
      CM. The mean average RNFL thickness was 83 +/- 10.5 MUm in CM patients and 85 +/-
      9.6 MUm in healthy controls (p = 0.648), but superior quadrant RNFL thickness in
      the CM patients was significantly lower than healthy controls. The mean superior
      RNFL thickness was 86 +/- 6.7 MUm in CM patients and 108 +/- 7.3 MUm in controls
      (p < 0.001). Illness duration and frequency of the attacks were not affected by
      RNFL thickness. No significant differences were detected in macular changes
      between CM patients and healthy controls. In our study, the thickness of superior
      RNFL was found to be thinner in CM patients. This implies that longitudinal
      follow-up is needed to clarify whether RNFL thinning, in migraine patients, is
      related to a progressive loss of axons and retinal ganglion cells.

PMID- 23135781
TI  - Fatal rhinocerebral mucormycosis with intracavernous carotid aneurysm and
      thrombosis: a late complication of transsphenoidal surgery?
AB  - Mucormycosis is a rare opportunistic fungal infection. Rhinocerebral form of the
      disease mainly affects diabetic or immunocompromised patients. Mucormycosis have
      specific tropism for blood vessels leading to mucorthrombosis and less often to
      mycotic aneurysms. We report on a patient initially presenting with a severe
      sphenoid sinusopathy, who progressively evolved to cavernous sinus syndrome,
      internal carotid aneurysm followed by spontaneous thrombosis, chronic meningitis
      and ultimately fatal hypertensive hydrocephalus. Necropsy revealed a purulent
      infiltrate containing thin-walled, aseptate, right-angle branching, hyphae
      consistent with mucormycosis. His only relevant previous medical history was a
      transsphenoidal surgery for pituitary macroadenoma 21 years before. We
      hypothesize that post-surgical mucosal changes in the sphenoid sinus have been a
      favoring factor for delayed and invasive mucor infection.

PMID- 23135782
TI  - Polysomnographic and long-term video electroencephalographic evaluation of cases
      presenting with parasomnias.
AB  - The aim of this study is to evaluate the clinical, electroencephalographic and
      polysomnographic features of patients presenting with parasomnias. Cases who were
      admitted for differentiating parasomnias from epilepsy were included in the
      study. Clinical features of cases were recorded and routine sleep
      electroencephalography was obtained from all cases. Cases whose symptoms strongly
      suggested nocturnal seizure underwent all night video electroencephalography
      monitoring. Polysomnography was obtained to evaluate the quality of breathing
      from patients whose symptoms suggested obstructive sleep apnea. Twenty-three
      patients with no neurological disorder were included in the study. The mean age
      of the patients was 11.7 +/- 2.8 [7-17] years. Twelve patients (52 %) presented
      with sleep terrors and 11 patients (48 %) presented with sleep walking. All of
      the patients underwent a routine sleep electroencephalographic study and 15
      patients (65 %) whose symptoms strongly suggested nocturnal epilepsy underwent
      long-term video electroencephalographic evaluation. Ten patients (43 %) underwent
      polysomnographic study. Three patients (20 %) who underwent long-term video
      electroencephalographic evaluation were diagnosed to have nocturnal frontal lobe
      epilepsy and two patients (20 %) who underwent polysomnography had pathological
      sleep apnea. Eleven patients (48 %) had a psychiatric disorder like major
      depression, anxiety disorder, hyperactivity disorder and obsessive-compulsive
      disorder. Childhood cases presenting with parasomnias should be searched for
      nocturnal epileptic disorders, sleep disordered breathing and psychiatric
      disorders.

PMID- 23135783
TI  - The dichloromethane extract of the ethnomedicinal plant Neurolaena lobata
      inhibits NPM/ALK expression which is causal for anaplastic large cell
      lymphomagenesis.
AB  - The present study investigates extracts of Neuolaena lobata, an anti-protozoan
      ethnomedicinal plant of the Maya, regarding its anti-neoplastic properties.
      Firstly, extracts of increasing polarity were tested in HL-60 cells analyzing
      inhibition of cell proliferation and apoptosis induction. Secondly, the most
      active extract was further tested in anaplastic large cell lymphoma (ALCL) cell
      lines of human and mouse origin. The dichloromethane extract inhibited
      proliferation of HL-60, human and mouse ALCL cells with an IC50 of ~2.5, 3.7 and
      2.4 ug/ml, respectively and arrested cells in the G2/M phase. The extract induced
      the checkpoint kinases Chk1 and Chk2 and perturbed the orchestrated expression of
      the Cdc25 family of cell cycle phosphatases which was paralleled by the
      activation of p53, p21 and downregulation of c-Myc. Importantly, the expression
      of NPM/ALK and its effector JunB were drastically decreased, which correlated
      with the activation of caspase 3. Subsequently also platelet derived growth
      factor receptor beta was downregulated, which was recently shown to be
      transcriptionally controlled by JunB synergizing with ALK in ALCL development. We
      show that a traditional healing plant extract downregulates various oncogenes,
      induces tumor suppressors, inhibits cell proliferation and triggers apoptosis of
      malignant cells. The discovery of the 'Active Principle(s)' is warranted.

PMID- 23135784
TI  - Enhanced spatio-temporal alignment of plantar pressure image sequences using B
      splines.
AB  - This article presents an enhanced methodology to align plantar pressure image
      sequences simultaneously in time and space. The temporal alignment of the
      sequences is accomplished using B-splines in the time modeling, and the spatial
      alignment can be attained using several geometric transformation models. The
      methodology was tested on a dataset of 156 real plantar pressure image sequences
      (3 sequences for each foot of the 26 subjects) that was acquired using a common
      commercial plate during barefoot walking. In the alignment of image sequences
      that were synthetically deformed both in time and space, an outstanding accuracy
      was achieved with the cubic B-splines. This accuracy was significantly better (p
      < 0.001) than the one obtained using the best solution proposed in our previous
      work. When applied to align real image sequences with unknown transformation
      involved, the alignment based on cubic B-splines also achieved superior results
      than our previous methodology (p < 0.001). The consequences of the temporal
      alignment on the dynamic center of pressure (COP) displacement was also assessed
      by computing the intraclass correlation coefficients (ICC) before and after the
      temporal alignment of the three image sequence trials of each foot of the
      associated subject at six time instants. The results showed that, generally, the
      ICCs related to the medio-lateral COP displacement were greater when the
      sequences were temporally aligned than the ICCs of the original sequences. Based
      on the experimental findings, one can conclude that the cubic B-splines are a
      remarkable solution for the temporal alignment of plantar pressure image
      sequences. These findings also show that the temporal alignment can increase the
      consistency of the COP displacement on related acquired plantar pressure image
      sequences.

PMID- 23135785
TI  - Microleakage of Er:YAG laser and dental bur prepared cavities in primary teeth
      restored with different adhesive restorative materials.
AB  - The purpose of this study was to evaluate and compare the effect of
      erbium:yttrium-aluminum-garnet (Er:YAG) laser irradiation and conventional dental
      bur cavity preparation on in vitro microleakage of class V cavities restored with
      different adhesive restorative materials and two types of self-etching adhesives
      in primary teeth. Standard class V cavities were prepared on 80 extracted
      primary, and the teeth were randomly divided into eight subgroups prepared either
      by dental bur or Er:YAG laser irradiation and then restored with self-cured glass
      ionomer (GI), resin-modified glass ionomer (RMGI), resin composite and Clearfil
      SE Bond (two-step self-etching adhesive), and resin composite and Clearfil S3
      Bond (one-step self-etching adhesive). Restorations were finished and stored in
      distilled water at 37  degrees C for 24 h and then subjected to thermocycling.
      All the teeth were sealed with nail varnish, placed in a silver nitrate solution,
      and then vertically cut in a buccolingually direction. Subsequently, the
      specimens were evaluated for gingival and occlusal microleakage using a
      stereomicroscope. Data were analyzed using Kruskal-Wallis test followed by Mann
      Whitney test. Wilcoxon test was used for comparing occlusal microleakage with
      gingival microleakage at p < 0.05. A higher degree of occlusal and gingival
      microleakage values for the teeth restored with GI or RMGI was obtained by both
      preparation methods compared with that of resin composites and the two self
      etching primers. Er:YAG laser irradiation resulted in a significantly higher
      degree of microleakage only at the gingival margins for teeth restored with GI or
      RMGI, or composite and Clearfil S3 Bond compared with the bur preparation. The
      Er:YAG laser-prepared teeth restored with composite and Clearfil SE Bond
      demonstrated a better marginal seal on occlusal and gingival margins compared
      with that of bur-prepared cavities. The degree of microleakage in class V
      cavities was affected by the type of adhesive restorative materials, type of self
      etching adhesive, cavity margin location, and tooth preparation method either by
      Er:YAG laser or dental bur.

PMID- 23135786
TI  - Effect of a DPSS laser on the shear bond strength of ceramic brackets with
      different base designs.
AB  - This study evaluated the shear bond strength (SBS) and adhesive remnant index
      (ARI) of ceramic brackets with different base designs using a 473-nm diode-pumped
      solid-state (DPSS) laser to test its usefulness as a light source. A total of 180
      caries-free human premolars were divided into four groups according to the base
      designs: microcrystalline, crystalline particle (CP), dovetail, and mesh. For
      each base design, teeth were divided into three different subgroups for light
      curing using three different light-curing units (LCUs) (quartz-tungsten-halogen
      unit, light-emitting diode unit, and a DPSS laser of 473 nm). Applied light
      intensities for the DPSS laser and the other LCUs were approximately 630 and 900
      mW/cm(2), respectively. Stainless steel brackets with a mesh design served as
      controls. The failure modes of debonded brackets were scored using ARI. As a
      result, brackets bonded using the DPSS laser had the highest SBS values (16.5
      27.3 MPa) among the LCUs regardless of base design. Regarding base designs, the
      CP groups showed the highest SBS values (22.9-27.3 MPa) regardless of LCU.
      Furthermore, stainless steel brackets with a mesh design had the lowest SBS
      values regardless of LCU. In many cases, brackets bonded using the DPSS laser had
      higher ARI scores and had more adhesive on their bases than on tooth surfaces.
      The study shows that the 473-nm DPSS laser has considerable potential for bonding
      ceramic brackets at lower light intensities than the other light-curing units
      examined.

PMID- 23135787
TI  - Natural killer cell immunity after transplantation.
AB  - Transplantation immunology has traditionally focused on adaptive, i.e., T- and B
      cell reactions. More recently, natural killer (NK) cells were also recognised as
      playing an important role after transplantation of solid organs and
      haematopoietic stem cells. NK cells recognise "cell stress" induced by viral
      replication and tumour transformation via activating receptors, and are
      negatively regulated by the interaction between inhibitory molecules and
      autologous human leukocyte antigens (HLA). The most important inhibitory
      molecules belong to the family of killer cell immunoglobulin-like receptors
      (KIR). Differences in the inhibitory KIR/HLA interaction between stem cell donor
      and patient may lead to beneficial NK cell alloreactivity, resulting in specific
      graft-versus-tumour reactions, which occur in the absence of graft-versus-host
      disease. The immaturity of NK cells produced by the stem cell graft early after
      transplantation has led to different approaches of adoptive transfer of NK cells
      to further increase tumour control. The function and role of activating KIR
      receptors is less clear. Recent data have suggested, that activating KIR may also
      contribute to anti-tumour immunity after stem cell transplantation, as patients
      transplanted from donors carrying high numbers of activating KIR receptor genes
      show reduced relapse rates. In particular, protection from post-transplant
      disease relapse was demonstrated in transplants carried out from donors carrying
      the activating KIR2DS1 receptor, if the recipients also expressed the KIR2DS1
      ligand HLA-C2. In conclusion, NK cells have been firmly established in the last
      two decades as relevant players in transplant immunology, which can critically
      determine the outcome of haematopoietic stem cell grafts.

PMID- 23135788
TI  - Increased fetal insulin concentrations for one week fail to improve insulin
      secretion or beta-cell mass in fetal sheep with chronically reduced glucose
      supply.
AB  - Maternal undernutrition during pregnancy and placental insufficiency are
      characterized by impaired development of fetal pancreatic beta-cells. Prolonged
      reduced glucose supply to the fetus is a feature of both. It is unknown if
      reduced glucose supply, independent of other complications of maternal
      undernutrition and placental insufficiency, would cause similar beta-cell
      defects. Therefore, we measured fetal insulin secretion and beta-cell mass
      following prolonged reduced fetal glucose supply in sheep. We also tested whether
      restoring physiological insulin concentrations would correct any beta-cell
      defects. Pregnant sheep received either a direct saline infusion (CON = control,
      n = 5) or an insulin infusion (HG = hypoglycemic, n = 5) for 8 wk in late
      gestation (75 to 134 days) to decrease maternal glucose concentrations and reduce
      fetal glucose supply. A separate group of HG fetuses also received a direct fetal
      insulin infusion for the final week of the study with a dextrose infusion to
      prevent a further fall in glucose concentration [hypoglycemic + insulin (HG+I), n
      = 4]. Maximum glucose-stimulated insulin concentrations were 45% lower in HG
      fetuses compared with CON fetuses. beta-Cell, pancreatic, and fetal mass were
      50%, 37%, and 40% lower in HG compared with CON fetuses, respectively (P < 0.05).
      Insulin secretion and beta-cell mass did not improve in the HG+I fetuses. These
      results indicate that chronically reduced fetal glucose supply is sufficient to
      reduce pancreatic insulin secretion in response to glucose, primarily due to
      reduced pancreatic and beta-cell mass, and is not correctable with insulin.

PMID- 23135789
TI  - Isotopic and modeling investigation of long-term protein turnover in rat tissues.
AB  - Fractional synthesis rates (FSR) of tissue proteins (P) are usually measured
      using labeled amino acid (AA) tracer methods over short periods of time under
      acute, particular conditions. By combining the long-term and non-steady-state
      (15)N labeling of AA and P tissue fractions with compartmental modeling, we have
      developed a new isotopic approach to investigate the degree of compartmentation
      of P turnover in tissues and to estimate long-term FSR values under sustained and
      averaged nutritional and physiological conditions. We measured the rise-to
      plateau kinetics of nitrogen isotopic enrichments (delta(15)N) in the AA and P
      fractions of various tissues in rats for 2 mo following a slight increase in diet
      delta(15)N. Using these delta(15)N kinetics and a numerical method based on a two
      compartment model, we determined reliable FSR estimates for tissues in which P
      turnover is adequately represented by such a simple precursor-product model. This
      was the case for kidney, liver, plasma, and muscle, where FSR estimates were 103,
      101, 58, and 11%/day, respectively. Conversely, we identified tissues, namely,
      skin and small intestine, where P turnover proved to be too complex to be
      represented by a simple two-compartment model, evidencing the higher level of
      subcompartmentation of the P and/or AA metabolism in these tissues. The present
      results support the value of this new approach in gaining cognitive and practical
      insights into tissue P turnover and propose new and integrated FSR values over
      all individual precursor AA and all diurnal variations in P kinetics.

PMID- 23135790
TI  - Neck circumference is correlated with triglycerides and inversely related with
      HDL cholesterol beyond BMI and waist circumference.
AB  - BACKGROUND: Neck circumference, beyond a measure of obesity, is a unique fat
      depot with increasing significance. This study aimed to investigate the
      association between neck circumference and biomarkers, indicators of
      cardiovascular risk. METHODS: During 2009, 490 volunteers (46 +/- 16 years, 40%
      men) were consecutively enrolled to the study (participation rate 85%).
      Biochemical analyses were performed through established procedures, and after 12
      h fasting and glucose, total cholesterol, high-density lipoprotein and low
      density lipoprotein cholesterol, triglycerides, cystatin C, uric acid and high
      sensitivity C-reactive protein were measured. Anthropometric, lifestyle and
      dietary characteristics were also recorded to account for potential confounders.
      Additive linear and logistic regression models were used to evaluate the
      association between neck circumference and biomarkers of cardiometabolic risk.
      RESULTS: A positive association between neck circumference and systolic and
      diastolic blood pressure, glucose, triglycerides, uric acid and high-sensitivity
      C-reactive protein, and a negative association with high-density lipoprotein
      cholesterol were revealed (all ps < 0.05); models were adjusted for age, gender,
      years of school, smoking, physical activity status, MedDietScore and alcohol
      intake. The relationship between neck circumference and high-density lipoprotein
      cholesterol, glucose, triglycerides and uric acid remained significant when
      models were further stratified by body mass index class and abnormal waist
      circumference. CONCLUSION: Neck circumference was found to be a powerful
      indicator of atherogenic dyslipidaemia above and beyond central obesity
      indicators.

PMID- 23135791
TI  - Disk degeneration of the upper lumbar disks is associated with hip pain.
AB  - PURPOSE: A possible cause of hip pain is the presence of radiating pain from the
      higher lumbar spine. Identification of factors associated with hip pain arising
      from the lumbar spine would aid the physician. The first step in identifying
      possible factors is to look at the association between hip pain and
      osteoarthritis of the lumbar spine. METHODS: In an open population based study of
      people 55 years and older (Rotterdam study), 2,819 lumbar radiographs were scored
      for the presence and severity of individual radiographic features of disk
      degeneration. Hip osteoarthritis was scored on anteroposterior pelvic
      radiographs, and questionnaires including self-reported hip pain were taken.
      Logistic regression adjusted for possible confounders was used to determine the
      association between self-reported hip pain and the individual radiographic
      features of lumbar disk degeneration. RESULTS: The presence of dis space
      narrowing grade >=1 at level L1/L2 was significantly associated with hip pain in
      the last month (men OR = 2.0; 95 % CI 1.1-3.8 and women OR = 1.7; 95 % CI 1.1
      2.5). The presence of disk space narrowing grade >=1 at level L2/L3 was only
      significantly associated with hip pain in women. The strength of the associations
      increased for self-reported chronic hip pain, especially in men (L1/L2 OR = 2.5;
      95 % CI 1.3-5.0). The presence of disk space narrowing at the lower levels
      (L3/L4/L5/S1) was not significantly associated with hip pain. CONCLUSION: Our
      data provide evidence for an association between hip pain and disk space
      narrowing at disk level L1/L2 and L2/L3. In case of uncertainty of the cause of
      hip pain, evaluation of lumbar radiographs may help to identify those hip pain
      patients who might have pain arising from the lumbar spine.

PMID- 23135792
TI  - Vertebral rotation in adolescent idiopathic scoliosis calculated by radiograph
      and back surface analysis-based methods: correlation between the Raimondi method
      and rasterstereography.
AB  - PURPOSE: The aim of the present research is to evaluate the relationship between
      an X-ray-based method (i.e. the Raimondi method) and rasterstereography in the
      evaluation of vertebral rotation (VR) in a sample of adolescent idiopathic
      scoliosis (AIS) patients. METHODS: A total of 25 patients (9 males; mean age 14
      +/- 3 years; mean height 160.7 +/- 11.9 cm; mean weight 52.4 +/- 10.7 kg) were
      considered for the present analysis. The mean Cobb angle was 30 degrees  +/- 9
      degrees . The evaluation of VR on radiographs was made using the Raimondi method
      regolo (Marrapese Editore--Demi S.r.1., Rome). Rasterstereography was performed
      by means of Formetric 4D((r)) (Diers International GmbH, Schlangenbad, Germany).
      Correlations between rasterstereographic and radiographic measurement of VR were
      calculated, both for the whole sample and for thoracic and lumbar spinal segments
      considered separately, as well as for subgroups of patients with a Cobb angle <30
      degrees  and >= 30 degrees  using Spearman's correlation coefficient by rank (r
      (s)). RESULTS: When applied to the entire spine, measurement of VR by means of
      the two methods highlighted a significant correlation in the whole group (r =
      0.52; p < 0.0001), as well as in the <30 degrees  Cobb (r = 0.47; p = 0.0001) and
      >= 30 degrees  Cobb (r = 0.42; p < 0.0001) subgroups. A significant correlation
      was found also when lumbar and thoracic VR were considered as separated groups (r
      = 0.30, p = 0.024 and r = 0.47, p = 0.002, respectively). CONCLUSIONS:
      Rasterstereographic evaluation of VR shows a good correlation with the Raimondi
      method, thereby confirming the possibility to use this non-invasive method for
      deformity assessment in AIS patients.

PMID- 23135793
TI  - Aneurysmal bone cyst of the mobile spine: the therapeutic role of embolization.
AB  - PURPOSE: Our aim is to define the role of embolization in the treatment of
      aneurysmal bone cyst of the spine in order to include this option in the decision
      making process. METHODS: From April 2004 to November 2009, seven patients with
      primary aneurysmal bone cyst of the mobile spine treated by embolization have
      been prospectively followed-up. All clinical presentations and imagings were
      recorded. There are many options of embolic agent and techniques used, but all
      aim to devascularize the tumor. The therapeutic protocol includes: embolization
      repeated every 8 weeks until the appearance of radiographic signs of healing.
      Complications, rate of healing and clinical outcome were analyzed. RESULTS: The
      number of embolizations varied from one to a maximum of seven without related
      intra- or post-operative complications. One patient, after four selective
      arterial embolizations, underwent direct percutaneous injection of embolic agents
      into the cyst. A clinical and radiographical response was achieved in all
      patients who were found alive and completely free of disease at mean follow-up of
      46 months after last treatment and nobody crossed to surgical option. CONCLUSION:
      Embolization seems to be the first option for spinal aneurysmal bone cyst
      treatment because of the best cost-to-benefit ratio. It is indicated in intact
      aneurysmal bone cyst, when diagnosis is certain, when technically feasible and
      safe and when no pathologic fracture or neurologic involvements are found. If
      embolization fails, other options for treatment would still be available.

PMID- 23135794
TI  - Developmental and diurnal expression of the synaptosomal-associated protein 25
      (Snap25) in the rat pineal gland.
AB  - Snap25 (synaptosomal-associated protein) is a 25 kDa protein, belonging to the
      SNARE-family (soluble N-ethylmaleimide-sensitive factor attachment protein
      receptors) of proteins, essential for synaptic and secretory vesicle exocytosis.
      Snap25 has by immunohistochemistry been demonstrated in the rat pineal gland but
      the biological importance of this is unknown. In this study, we demonstrate a
      high expression of mRNA encoding Snap25 in all parts of the rat pineal complex,
      the superficial-, and deep-pineal gland, as well as in the pineal stalk. Snap25
      showed a low pineal expression during embryonic stages with a strong increase in
      expression levels just after birth. The expression showed no day/night
      variations. Neither removal of the sympathetic input to the pineal gland by
      superior cervical ganglionectomy nor bilateral decentralization of the superior
      cervical ganglia significantly affected the expression of Snap25 in the gland.
      The pineal expression levels of Snap25 were not changed following intraperitoneal
      injection of isoproterenol. The strong expression of Snap25 in the pineal gland
      suggests the presence of secretory granules and microvesicles in the rat
      pinealocyte supporting the concept of a vesicular release. At the transcriptional
      level, this Snap25-based release mechanism does not exhibit any diurnal
      rhythmicity and is regulated independently of the sympathetic nervous input to
      the gland.

PMID- 23135795
TI  - Phases of health promotion implementation into the Scottish school system.
AB  - Schools have been identified as ideal settings for health promotion (HP) among
      children, adolescents and school staff. Most European countries have established
      strategies to implement HP into their school system, however, little is known
      about these national strategies and how effective they have been. School HP
      implementation concerns processes of adoption, adaptation and operation of a
      complex intervention into a complex setting. This study analyses the processes
      that have led to school HP implementation in Scotland from the 1980s until now to
      identify key factors which facilitated and supported effective implementation. In
      the tradition of case-study research, 14 interviews with representatives of
      national and local organizations involved in school health, as well as with
      school staff were conducted. Furthermore, policy documents, reports and
      guidelines were collected. The data were analysed following a Grounded Theory
      approach. Four phases of school HP implementation into the Scottish school system
      were identified: (i) getting started (1980s-1998), (ii) political will and
      strategic vision (1999-2001), (iii) national leadership (2002-2008), and (iv)
      integration and embedding into education system (2008-ongoing). Throughout the
      phases political will and committed actors, the strategy/tradition to give power
      to the local authorities and individual schools, and the establishment of
      partnerships and ownership have supported implementation. Scotland is an
      interesting case giving important insights into the ways and possibilities of
      negotiating an interdisciplinary and cross-sectoral theme such as HP in schools.
      Further research concerning different political systems and national
      implementation processes is important to widen the understanding of national
      implementation strategies of school HP. 

PMID- 23135796
TI  - Short multiwall carbon nanotubes promote neuronal differentiation of PC12 cells
      via up-regulation of the neurotrophin signaling pathway.
AB  - Numerous unique properties of carbon nanotubes make them attractive for
      applications in neurobiology such as drug delivery, tissue regeneration, and as
      scaffolds for neuronal growth. In this study, the critical roles of the length of
      multiwall carbon nanotubes (MWCNTs) on a neuronal-like model cell line PC12 cells
      are investiaged. Incubation of PC12 cells with carboxylated MWCNTs did not
      significantly affect cellular morphology and viability at lower concentrations.
      Short MWCNTs show higher cellular uptake and more obvious removal compared to
      longer ones, which can result in higher ability to promote PC12 cell
      differentiation. Pre-incubation of short MWCNTs can up-regulate the expression of
      neurotrophin signaling pathway-associated TrkA/p75 receptors and Pincher/Gap43/TH
      proteins, which might be the underlying mechanism for the improved
      differentiation in PC12 cells. The current results provide insight for future
      applications of MWCNTs in neuron drug delivery and neurodegenerative disease
      treatment.

PMID- 23135797
TI  - A highly active and coke-resistant steam reforming catalyst comprising uniform
      nickel-iron alloy nanoparticles.
AB  - Doing fine with Ni-Fe: The calcination and reduction of a hydrotalcite precursor
      containing Ni and Fe ions gives uniform Ni-Fe alloy nanoparticles mixed with
      Mg(Ni, Fe, Al)O particles. The uniformity of the Ni-Fe alloy nanoparticles is
      connected to the catalyst's high activity and resistance to coke formation in
      toluene and phenol steam reforming reactions.

PMID- 23135798
TI  - Is it really Aeromonas hydrophila?

PMID- 23135799
TI  - Reply: is it really Aeromonas hydrophila?

PMID- 23135800
TI  - Representing rebellion: memory and social conflict in sixteenth-century England.
AB  - This paper takes key insights from social psychologists and interrogates them as
      methodological tools for historians, applying these theories to a large-scale
      uprising that occurred in southern England in 1549. In a social order based on
      notions of paternalism and deference, a diverse band of rebels were able to forge
      an alliance strong enough to pose a serious threat to local authorities in
      Norwich. Social psychological approaches to collective memory and evolving social
      representations are deployed to highlight contested memories of rebellion as
      central to Tudor state formation, and to understand how a rebel group with many
      competing interests was able to sustain their alliance. I argue that the
      imperative to understand individual behaviour in a collective context illuminates
      the way that this group could form a vision of the world which contradicted
      deferential social ideals without ranging themselves against central government.
      The article also suggests ways in which historical approaches can inform social
      psychological concepts.

PMID- 23135801
TI  - Social representations of memory and gender in later medieval England.
AB  - Social representations in later medieval culture have attracted little attention
      amongst psychologists, pre-dating the development of the so-called 'public
      sphere' in the eighteenth century. In addition, the association of pre-modern
      societies with 'traditional' modes of communication in social psychology places
      implicit limits on areas that may be studied through the lens of social
      representation theory. This article analyses the way in which knowledge
      circulated in late medieval society, noting initially the plural nature of
      representations of events and marginal groups, and the myriad channels through
      which beliefs were consolidated. In later medieval England perceptions of the
      past depended on collective and group memory, with customary rights and local
      histories forged through 'common knowledge', hearsay and the opinions of
      'trustworthy men' of the village. The final section of this commentary provides
      an analysis of testimony from the late medieval church courts, in which witnesses
      articulated gender ideologies that reflected perceptions drawn from everyday
      life. Social representations of women were thus deployed in ecclesiastical suits,
      on the one hand supporting evidence of female witnesses and on the other
      justifying misogynistic stereotypes of women's behaviour.

PMID- 23135802
TI  - 'Historicising common sense'.
AB  - This essay is an expanded set of comments on the social psychology papers written
      for the special issue on History and Social Psychology. It considers what social
      psychology, and particularly the theory of social representations, might offer
      historians working on similar problems, and what historical methods might offer
      social psychology. The social history of thinking has been a major theme in
      twentieth and twenty-first century historical writing, represented most recently
      by the genre of 'cultural history'. Cultural history and the theory of social
      representations have common ancestors in early twentieth-century social science.
      Nevertheless, the two lines of research have developed in different ways and are
      better seen as complementary than similar. The theory of social representations
      usefully foregrounds issues, like social division and change over time, that
      cultural history relegates to the background. But for historians, the theory of
      social representations seems oddly fixated on comparing the thought styles
      associated with positivist science and 'common sense'. Using historical analysis,
      this essay tries to dissect the core opposition 'science : common sense' and
      argues for a more flexible approach to comparing modes of thought.

PMID- 23135803
TI  - Haemolysis risk in methylene blue treatment of G6PD-sufficient and G6PD-deficient
      West-African children with uncomplicated falciparum malaria: a synopsis of four
      RCTs.
AB  - PURPOSE: Methylene blue (MB), which was recently tested in a number of clinical
      malaria studies in Burkina Faso, is currently investigated for its benefit when
      added to artemisinin-based combination therapy. Together with a number of other
      antimalarials, MB is on the list of drugs which potentially induce haemolysis in
      patients with G6PD deficiency. Ruling out safety concerns is of major importance
      during drug development. METHODS: A pooled analysis was performed with patient
      data from four clinical studies conducted in West African children with
      falciparum malaria between 2003 and 2007. The primary endpoints were haemoglobin
      levels over time as well as haemolysis in G6PD-deficient (n = 199) and G6PD
      sufficient (n = 806) children treated with MB-containing (n = 844) compared to
      children without MB-containing (n = 161) drug regimens. RESULTS: In the chosen
      model, the haemoglobin time course was significantly influenced by the G6PD
      genotype and the MB dose. In children with hemi- or homozygous G6PD (A-)
      deficiency, MB treatment with 15 mg/kg per day was associated with a significant
      reduction in Hb values which reached a minimum of 8.5 g/dl. Two episodes of
      haemolysis occurred (out of 1005 children); one in a girl heterozygous for G6PD
      deficiency and one in a hemizygous boy, both had received MB. CONCLUSIONS: MB
      treatment of malaria in Africa is associated with slightly reduced haemoglobin
      values in children with a full G6PD defect compared to non-G6PD deficient
      children. This effect appears to be of limited clinical relevance but needs to be
      monitored.

PMID- 23135804
TI  - HIV prevalence overall and among high-HIV-risk behaviorally defined subgroups
      among heterosexuals at community-based venues in a Mid-Atlantic, US City.
AB  - A clear understanding of local transmission dynamics is a prerequisite for the
      design and implementation of successful HIV prevention programs. There is a
      tremendous need for such programs geared towards young African-American women
      living in American cities with syndemic HIV and injection drug use. In some of
      these American cities, including Baltimore, the HIV prevalence rate among young
      African-American women is comparable to that in some African nations. High-risk
      heterosexual sex, i.e., sex with an injection drug user or sex with someone known
      to have HIV, is the leading risk factor for these young women. Characterizing
      transmission dynamics among heterosexuals has been hampered by difficulty in
      identifying HIV cases in these settings. The case identification method described
      in this paper was designed to address challenges encountered by previous
      researchers, was based on the Priorities for Local AIDS Cases methodology, and
      was intended to identify a high number of HIV cases rather than achieve a
      representative sample (Weir et al., Sex Transm Infect 80(Suppl 2):ii63-8, 2004.
      Through a three-phase process, 87 venues characterized as heterosexual sex
      partner meeting sites were selected for participant recruitment in Baltimore, MD.
      One thousand six hundred forty-one participants were then recruited at these 87
      venues, administered a behavioral risk questionnaire, and tested for HIV. The HIV
      prevalence was 3 % overall, 3 % among males, and 4 % among females and ranged
      from 1.7 to 22.6 % among high-HIV-risk subgroups. These findings indicate that
      attributing HIV transmission to high-risk heterosexual sex vs. other high-HIV
      risk behaviors would be difficult. Moving beyond individual risk profiles to
      characterize the risk profile of venues visited by heterosexuals at high risk of
      HIV acquisition may reveal targets for HIV transmission prevention and should be
      the focus of future investigations. 

PMID- 23135805
TI  - Ifosfamide-induced neurotoxicity reversal with continuous veno-venous
      hemodialysis. A case report.
AB  - Ifosfamide is an alkylating agent used to treat different types of malignancies
      including lymphomas, sarcomas and germinal cell tumors. Symptoms of ifosfamide
      neurotoxicity can range from mild confusion, dizziness and hallucination to overt
      encephalopathy. Various treatment options like methylene blue, albumin infusion
      and rarely hemodialysis have been used to treat ifosfamide neurotoxicity. We
      hereby report a case of a patient with relapsed diffuse large B cell lymphoma who
      received methylene blue after experiencing acute renal failure and encephalopathy
      due to ifosfamide with no improvement. The prompt use of hemodialysis in this
      case has led to reversal of both renal failure and neurotoxicity. 

PMID- 23135806
TI  - Cetuximab hypersensitivity infusion reactions: Incidence and risk factors.
AB  - INTRODUCTION: Cetuximab is a chimeric mouse-human (30:70) IgG1 monoclonal
      antibody that competitively inhibits the binding of epidermal growth factor.
      Cetuximab is generally well tolerated; however, hypersensitivity infusion
      reactions have been reported. The incidence at the University of Oklahoma was
      currently unknown, though anecdotally high. The purpose of this study was to
      determine the incidence of severe HIRs and secondarily to determine risk factors
      for cetuximab-induced hypersensitivity infusion reactions. METHODS AND RESULTS: A
      retrospective chart review was conducted and included all patients that received
      cetuximab from 2005 to 2010 at the outpatient clinics of the Oklahoma University
      Health Sciences Center. A total of 153 patients were included in the analysis.
      The overall incidence proportion of severe hypersensitivity infusion reactions
      was 12.4%. Male patients had an increased incidence of severe hypersensitivity
      infusion reactions compared to female patients (20.6% vs. 5%, p = 0.0036).
      Current smokers had an increased incidence of severe hypersensitivity infusion
      reactions of 23.6% when compared to never smokers or former smokers, p = 0.0012.
      Cervical cancer had a significantly decreased risk of severe hypersensitivity
      infusion reactions when compared to other tumor types (5.3% vs. 16.7%, p =
      0.0387). Multivariate analysis identified risk factors associated with severe
      HIRs to be: male gender, RR = 3.9, p = 0.01 and current smokers, RR = 3.98, p =
      0.0048. CONCLUSION: Patients at the University of Oklahoma had an increased
      incidence of severe hypersensitivity infusion reactions when compared to the
      national average. Male patients and current smokers were found to be at increased
      risk for severe hypersensitivity infusion reactions in our study. Further
      investigation is warranted.

PMID- 23135807
TI  - Quality control of next-generation sequencing library through an integrative
      digital microfluidic platform.
AB  - We have developed an automated quality control (QC) platform for next-generation
      sequencing (NGS) library characterization by integrating a droplet-based digital
      microfluidic (DMF) system with a capillary-based reagent delivery unit and a
      quantitative CE module. Using an in-plane capillary-DMF interface, a prepared
      sample droplet was actuated into position between the ground electrode and the
      inlet of the separation capillary to complete the circuit for an electrokinetic
      injection. Using a DNA ladder as an internal standard, the CE module with a
      compact LIF detector was capable of detecting dsDNA in the range of 5-100 pg/MUL,
      suitable for the amount of DNA required by the Illumina Genome Analyzer
      sequencing platform. This DMF-CE platform consumes tenfold less sample volume
      than the current Agilent BioAnalyzer QC technique, preserving precious sample
      while providing necessary sensitivity and accuracy for optimal sequencing
      performance. The ability of this microfluidic system to validate NGS library
      preparation was demonstrated by examining the effects of limited-cycle PCR
      amplification on the size distribution and the yield of Illumina-compatible
      libraries, demonstrating that as few as ten cycles of PCR bias the size
      distribution of the library toward undesirable larger fragments.

PMID- 23135808
TI  - Diagnosis, misdiagnosis, and associated diseases of achalasia in children and
      adolescents: a twelve-year single center experience.
AB  - PURPOSE: Although achalasia is a rare disorder in children, its symptom may mimic
      common childhood diseases. This study aimed to assess the diagnosis and
      management of achalasia in children and adolescents in a Brazilian single center
      during a 12-year period. METHODS: Patients with achalasia were identified from a
      database built during the period of January 2000-January 2012 from a Pediatric
      Gastroenterology reference center. Information regarding demographic data,
      clinical symptoms, diagnosis, treatment, and long-term follow-up were described.
      RESULTS: Thirteen patients were studied; median age was 7 (1-14) years. Most
      frequent symptoms were vomiting (84.6 %) and dysphagia (69.2 %). Weight loss
      occurred in 46.0 % of patients and chronic cough in 46.1 %. Associated disorders
      were Down's syndrome, Allgrove syndrome, and congenital central hypoventilation
      syndrome. Achalasia was misdiagnosed with anorexia nervosa. Six patients were
      previously treated as having gastroesophageal reflux disease and asthma. Five
      patients had pneumatic balloon dilation as initial therapy whereas five had
      esophageal myotomy. Finally, 11 patients had surgical therapy with a favorable
      follow-up. CONCLUSION: Achalasia symptoms may mimic common diseases in children,
      and therefore, may delay the diagnosis. This study emphasizes the importance of
      the clinical symptoms for the diagnosis of achalasia, mainly in those cases with
      associated disorders.

PMID- 23135810
TI  - Copper, BDNF and Its N-terminal domain: inorganic features and biological
      perspectives.
AB  - Brain-derived neurotrophic factor (BDNF) is a neurotrophin that influences
      development, maintenance, survival, and synaptic plasticity of central and
      peripheral nervous systems. Altered BDNF signaling is involved in several
      neurodegenerative disorders including Alzheimer's disease. Metal ions may
      influence the BDNF activity and it is well known that the alteration of Cu(2+)
      homeostasis is a prominent factor in the development of neurological pathologies.
      The N-terminal domain of BDNF represents the recognition site of its specific
      receptor TrkB, and metal ions interaction with this protein domain may influence
      the protein/receptor interaction. In spite of this, no data inherent the
      interaction of BDNF with Cu(2+) ions has been reported up to now. Cu(2+)
      complexes of the peptide fragment BDNF(1-12) encompassing the sequence 1-12 of N
      terminal domain of human BDNF protein were characterized by means of
      potentiometry, spectroscopic methods (UV/Vis, CD, EPR), parallel tempering
      simulations and DFT-geometry optimizations. Coordination features of the
      acetylated form, Ac-BDNF(1-12), were also characterized to understand the
      involvement of the terminal amino group. Whereas, an analogous peptide, BDNF(1
      12)D3N, in which the aspartate residue was substituted by an asparagine, was
      synthesized to provide evidence on the possible role of carboxylate group in
      Cu(2+) coordination. The results demonstrated that the amino group is involved in
      metal binding and the metal coordination environment of the predominant complex
      species at physiological pH consisted of one amino group, two amide nitrogen
      atoms, and one carboxylate group. Noteworthy, a strong decrease of the
      proliferative activity of both BDNF(1-12) and the whole protein on a SHSY5Y
      neuroblastoma cell line was found after treatment in the presence of Cu(2+). The
      effect of metal addition is opposite to that observed for the analogous fragment
      of nerve growth factor (NGF) protein, highlighting the role of specific domains,
      and suggesting that Cu(2+) may drive different pathways for the BDNF and NGF in
      physiological as well as pathological conditions.

PMID- 23135809
TI  - Exploring the genetic architecture of circulating 25-hydroxyvitamin D.
AB  - The primary circulating form of vitamin D is 25-hydroxy vitamin D (25(OH)D), a
      modifiable trait linked with a growing number of chronic diseases. In addition to
      environmental determinants of 25(OH)D, including dietary sources and skin
      ultraviolet B (UVB) exposure, twin- and family-based studies suggest that
      genetics contribute substantially to vitamin D variability with heritability
      estimates ranging from 43% to 80%. Genome-wide association studies (GWAS) have
      identified single nucleotide polymorphisms (SNPs) located in four gene regions
      associated with 25(OH)D. These SNPs collectively explain only a fraction of the
      heritability in 25(OH)D estimated by twin- and family-based studies. Using
      25(OH)D concentrations and GWAS data on 5,575 subjects drawn from five cohorts,
      we hypothesized that genome-wide data, in the form of (1) a polygenic score
      comprised of hundreds or thousands of SNPs that do not individually reach GWAS
      significance, or (2) a linear mixed model for genome-wide complex trait analysis,
      would explain variance in measured circulating 25(OH)D beyond that explained by
      known genome-wide significant 25(OH)D-associated SNPs. GWAS identified SNPs
      explained 5.2% of the variation in circulating 25(OH)D in these samples and there
      was little evidence additional markers significantly improved predictive ability.
      On average, a polygenic score comprised of GWAS-identified SNPs explained a
      larger proportion of variation in circulating 25(OH)D than scores comprised of
      thousands of SNPs that were on average, nonsignificant. Employing a linear mixed
      model for genome-wide complex trait analysis explained little additional
      variability (range 0-22%). The absence of a significant polygenic effect in this
      relatively large sample suggests an oligogenetic architecture for 25(OH)D.

PMID- 23135811
TI  - Continuous flow left ventricular assist devices: a valid option for heart failure
      patients.
AB  - Recent outstanding clinical advances with new mechanical circulatory systems
      (MCS) have led to additional strategies in the treatment of end stage heart
      failure (HF). Heart transplantation (HTx) can be postponed and for certain
      patients even replaced by smaller implantable left ventricular assist devices
      (LVAD). Mechanical support of the failing left ventricle enables appropriate
      hemodynamic stabilisation and recovery of secondary organ failure, often seen in
      these severely ill patients. These new devices may be of great help to bridge
      patients until a suitable cardiac allograft is available but are also discussed
      as definitive treatment for patients who do not qualify for transplantation. Main
      indications for LVAD implantation are bridge to recovery, bridge to
      transplantation or destination therapy. LVAD may be an important tool for
      patients with an expected prolonged period on the waiting list, for instance
      those with blood group 0 or B, with a body weight over 90 kg and those with
      potentially reversible secondary organ failure and pulmonary artery hypertension.
      However, LVAD implantation means an additional heart operation with inherent peri
      operative risks and complications during the waiting period. Finally, cardiac
      transplantation in patients with prior implantation of a LVAD represents a
      surgical challenge. This review summarises the current knowledge about LVAD and
      continuous flow devices especially since the latter have been increasingly used
      worldwide in the most recent years. The review is also based on the institutional
      experience at Berne University Hospital between 2000 and 2012. Apart from short
      term devices (Impella, Cardiac Assist, Deltastream and ECMO) which were used in
      approximately 150 cases, 85 pulsatile long-term LVAD, RVAD or bi-VAD and 44 non
      pulsatile LVAD (mainly HeartMateII and HeartWare) were implanted. After an
      initial learning curve, one-year mortality dropped to 10.4% in the last 58
      patients.

PMID- 23135812
TI  - Tunable carbon nanotube/protein core-shell nanoparticles with NIR- and enzymatic
      responsive cytotoxicity.
AB  - A unique procedure is developed to capture carbon nanotubes into closed virus
      like protein cages with a controllable shell. The cross-linked shell varies in
      thickness within ~10(0) -10(2)  nm, and can be entirely removed by enzyme
      degradation. The cytotoxicity is entirely suppressed, but can be promoted again
      by enzymes and near-infrared light. These hybrids can be decorated with
      functional inorganic nanoparticles or processed into nanocomposites.

PMID- 23135813
TI  - Organocatalytic amidation and esterification of aldehydes with activating
      reagents by a cross-coupling strategy.
AB  - Formation on demand: An organocatalytic cross-coupling reaction of aldehydes with
      N-hydroxyimides, hexafluoroisopropyl alcohol, and sulfonimides has been
      developed. The resulting active intermediates can be directly converted into
      amides or esters in one pot. This simple method makes use of readily available
      starting materials, and the newly discovered activating reagents should find
      broad application in the synthesis of amides and esters.

PMID- 23135814
TI  - Preclinical evaluation of injectable bone substitute materials.
AB  - Injectable bone substitutes (IBSs) represent an attractive class of ready-to-use
      biomaterials, both ceramic- and polymer-based, as they offer the potential
      benefit of minimally invasive surgery and optimal defect filling. Although in
      vitro assessments are the first step in the process of development, the safety
      and efficacy of an IBS strongly depend on validated preclinical research prior to
      clinical trials. However, the selection of a suitable preclinical model for
      performance evaluation of an IBS remains a challenge, as no gold standard exists
      to define the best animal model. In order to succeed in this attempt, we
      identified three stages of development, including (a) proof-of-principle, (b)
      predictive validity and (c) general scientific legitimacy, and the respective
      criteria that should be applied for such selection. The second part of this
      review provides an overview of commonly used animals for IBSs. Specifically,
      scientific papers published between January 1996 and March 2012 were retrieved
      that report the use of preclinical models for the evaluation of IBSs in
      situations requiring bone healing and bone augmentation. This review is meant not
      only to describe the currently available preclinical models for IBS application,
      but also to address critical considerations of such multi-factorial evaluation
      models (including animal species, strain, age, anatomical site, defect size and
      type of bone), which can be indicative but in most cases edge away from the human
      reality. Consequently, the ultimate goal is to guide researchers toward a more
      careful and meaningful interpretation of the results of experiments using animal
      models and their clinical applications.

PMID- 23135815
TI  - Novel spray-dried genipin-crosslinked casein nanoparticles for prolonged release
      of alfuzosin hydrochloride.
AB  - PURPOSE: To propose a simple method for the development of genipin-crosslinked
      casein micelles as a new delivery platform for prolonged release of alfuzosin
      hydrochloride. METHODS: Crosslinked casein micelles entrapping alfuzosin were
      transformed into solid redispersible nanoparticles via spray-drying technique
      with no need for drying adjuvants based on the stabilizing effect of casein.
      RESULTS: The nanoparticles displayed high production yields (86.99-94.63% w/w)
      with a reasonable drug incorporation efficiency ranged from 92.86 to 97.75%. The
      nanoparticles were readily reconstituted in aqueous solution with a particle size
      range of 122.1-260.0 nm and a zeta potential range of -21.6 to -36.6 mV
      indicating a good colloidal stability. No drug crystals were detectable in the
      scanning electron micrographs revealing successful encapsulation of alfuzosin
      into casein nanoparticles which was confirmed by differential scanning
      calorimetry. The nanoparticles succeeded in prolonging the drug release that
      could be controlled by modulating the genipin crosslinking degree. The release
      data showed a good fit into Higuchi release kinetics with non-Fickian type of
      drug diffusion. CONCLUSIONS: These results demonstrated that genipin-crosslinking
      combined with spray-drying technique could be used as a promising tool to develop
      solid redispersible casein nanoparticles with sustained drug release properties.

PMID- 23135816
TI  - Evaluation of wound healing potential of beta-chitin hydrogel/nano zinc oxide
      composite bandage.
AB  - PURPOSE: beta-chitin hydrogel/nZnO composite bandage was fabricated and evaluated
      in detail as an alternative to existing bandages. METHODS: beta-chitin hydrogel
      was synthesized by dissolving beta-chitin powder in Methanol/CaCl(2) solvent,
      followed by the addition of distilled water. ZnO nanoparticles were added to the
      beta-chitin hydrogel and stirred for homogenized distribution. The resultant
      slurry was frozen at 0 degrees C for 12 h. The frozen samples were lyophilized
      for 24 h to obtain porous composite bandages. RESULTS: The bandages showed
      controlled swelling and degradation. The composite bandages showed blood clotting
      ability as well as platelet activation, which was higher when compared to the
      control. The antibacterial activity of the bandages were proven against
      Staphylococcus aureus (S. aureus) and Escherichia coli (E.coli).
      Cytocompatibility of the composite bandages were assessed using human dermal
      fibroblast cells (HDF) and these cells on the composite bandages were viable
      similar to the Kaltostat control bandages and bare beta-chitin hydrogel based
      bandages. The viability was reduced to 50-60% in bandages with higher
      concentration of zinc oxide nanoparticles (nZnO) and showed 80-90% viability with
      lower concentration of nZnO. In vivo evaluation in Sprague Dawley rats (S.D.
      rats) showed faster healing and higher collagen deposition ability of composite
      bandages when compared to the control. CONCLUSIONS: The prepared bandages can be
      used on various types of infected wounds with large volume of exudates.

PMID- 23135817
TI  - Lecithin-based microemulsions for targeted delivery of ceramide AP into the
      stratum corneum: formulation, characterizations, and in vitro release and
      penetration studies.
AB  - PURPOSE: To improve the solubility and penetration of Ceramide AP (CER [AP]) into
      the stratum corneum that potentially restores the barrier function of aged and
      affected skin. METHODS: CER [AP] microemulsions (MEs) were formulated using
      lecithin, Miglyol(r) 812 (miglyol) and water-1,2 pentandiol (PeG) mixture as
      amphiphilic, oily and hydrophilic components, respectively. The nanostructure of
      the MEs was revealed using electrical conductivity, differential scanning
      calorimeter (DSC) and electron paramagnetic resonance (EPR) techniques. Photon
      correlation spectroscopy (PCS) was used to measure the sizes and shape of ME
      droplets. The release and penetration of the CER into the stratum corneum was
      investigated in vitro using a multi-layer membrane model. RESULTS: The MEs
      exhibited excellent thermodynamic stability (>2 years) and loading capacity (0.5%
      CER [AP]). The pseudo-ternary phase diagrams of the MEs were obtained and PCS
      results showed that the droplets are spherical in shape and bigger in size. In
      vitro investigations showed that the MEs exhibited excellent rate and extent of
      release and penetration. CONCLUSIONS: Stable lecithin-based CER [AP] MEs that
      significantly enhance the solubility and penetration of CER [AP] into the stratum
      corneum were developed. The MEs also have better properties than the previously
      reported polyglycerol fatty acid surfactant-based CER [AP] MEs.

PMID- 23135818
TI  - Lipid encapsulation of cationic polymers in hybrid nanocarriers reduces their non
      specific toxicity to breast epithelial cells.
AB  - PURPOSE: Clinical application of cationic polymers for delivery of nucleic acids
      has been limited by their toxicity. The purpose of this study is to evaluate
      whether the polymer-in-lipid hybrid nanotechnology recently developed for
      controlled siRNA delivery can tackle this toxicity issue by reducing exposure of
      the cellular components to free cationic polymers. METHODS: Lipid-polymer hybrid
      nanocarriers (LPNs) encapsulating complexes of hexadecylated polyethylenimine (H
      PEI) and biologically inactive siRNA in lipids were prepared at different lipid
      polymer ratios. Comparative toxicity of these LPNs and unencapsulated cationic
      materials on breast epithelial cell lines MDA-MB-231 and MCF-10a was evaluated.
      RESULTS: Even at a low lipid-polymer ratio (3:1 w/w), encapsulation of H-PEI
      improved its LC(50) values measured within hours by 3-5 fold, and caused less
      reduction in the colony-formation rates in 10-14 days. The observed reductions in
      the acute and delayed carrier toxicity were associated with significantly less
      membrane damages, improved mitochondrial functions, reduced reactive oxidative
      species production, and lower caspase-3 activity (all p < 0.05) without
      sacrificing the siRNA transfection efficiency. CONCLUSIONS: This study has
      validated the hybrid nanotechnology for controlled RNA delivery from a
      toxicological perspective. This is especially valuable if local or long-term RNA
      therapy is intended for which low carrier toxicity is essential.

PMID- 23135819
TI  - Drug loading of polymeric micelles.
AB  - PURPOSE: To gain mechanistic insights into drug loading and lyophilization of
      polymeric micelles. METHODS: PEGylated poly-4-(vinylpyridine) micelles were
      loaded with dexamethasone. Three different methods were applied and compared: O/W
      emulsion, direct dialysis, cosolvent evaporation. Micellar dispersions with the
      highest drug load were lyophilized with varying lyoprotectors: sucrose,
      trehalose, maltose, a polyvinylpyrrolidine derivative, and beta-cyclodextrin
      derivatives. For comparison, other PEGylated block copolymer micelles (PEGylated
      polylactic acid, polylactic acid-co-glycolic acid, polycaprolactone) were freeze
      dried. RESULTS: Drug loading via direct dialysis from acetone was a less
      effective loading method which led to dexamethasone loads <2% w/w. O/W emulsion
      technique from dichlormethane increased drug load up to ~13% w/w; optimized
      cosolvent evaporation increased load up to ~19% w/w. An important step for
      cosolvent evaporation was solubility screen of the drug prior to preparation.
      Loading was maintained upon lyophilization with beta-cyclodextrins which proved
      to be versatile stabilizers for other block copolymer micelles. CONCLUSION:
      Careful solvent selection prior to cosolvent evaporation was a beneficial
      approach to load hydrophobic drugs into polymeric micelles. Moreover, beta
      cyclodextrins could be used as versatile lyoprotectors for these micelles.

PMID- 23135820
TI  - Development of a bionic system for the simultaneous prediction of the
      release/absorption characteristics of enteric-coated formulations.
AB  - PURPOSE: To develop a new bionic system from an existing drug
      dissolution/absorption simulating system (DDASS) to simultaneously predict the
      release and absorption of enteric-coated formulations. METHODS: In accordance
      with the pH-dependent characteristics of enteric-coated formulations, the
      modified DDASS was designed to effectively imitate the pH change process of the
      formulations' transfer from stomach to intestine in vivo. Omeprazole enteric
      coated tablets were chosen as the model drug to verify the rationality and
      feasibility of the modified DDASS. The correlations between USP I system release
      and beagle dog absorption, as well as between modified DDASS elution/permeation
      and beagle dog absorption, were investigated by linear and nonlinear regression
      analyses, respectively. RESULTS: In vitro-in vivo correlation between the
      modified DDASS elution/permeation method and beagle dog absorption was higher
      than between the USP I system release and beagle dog absorption in both
      analytical methods. The ratio of first-order permeation rate constant to first
      order release rate constant was consistent with that from modified DDASS.
      CONCLUSIONS: The modified DDASS provided more information than the USP I system
      did in the evaluation of enteric-coated formulations. The proposed bionic system
      model could serve as a new method for improving drug effectiveness.

PMID- 23135821
TI  - Lamellar liquid crystalline phases for cutaneous delivery of Paclitaxel: impact
      of the monoglyceride.
AB  - PURPOSE: To develop liquid crystalline phases with monoglycerides, and assess
      whether the monoglyceride type favors cutaneous over transdermal paclitaxel
      delivery. METHODS: BRIJ-based lamellar phases were prepared with 0.5% paclitaxel
      and 20% of either monocaprylin (LP-MC), monomyristolein (LP-MM) or monoolein (LP
      MO). Skin electrical resistance, drug release and cutaneous delivery in vitro and
      in vivo were assessed. Viability of skin equivalents and release of IL-1alpha
      were assessed as indexes of irritation potential. RESULTS: An inverse
      relationship between monoglyceride acyl chain length and amount of paclitaxel
      delivered was observed. Although the largest paclitaxel amounts were delivered by
      LP-MC, all formulations delivered higher levels of drug in the skin (56-64-fold)
      than across the tissue. The superiority of LP-MC seems related to a stronger
      decrease in skin resistance (as an index of permeability), and not to increased
      drug release. LP-MC displayed similar penetration-enhancing ability in vivo, and
      a much lower irritation potential than Triton-X100 (a moderate irritant), leading
      to 3-fold higher skin equivalent viability and release of 60-fold less IL-1alpha.
      CONCLUSIONS: Even though LP-MC delivered the largest amounts of paclitaxel, all
      formulations provided similar cutaneous/transdermal delivery ratios, suggesting
      that changing the monoglyceride acyl chain length did not affect the balance
      between cutaneous and transdermal delivery.

PMID- 23135823
TI  - Extraction of PLGA-microencapsulated proteins using a two-immiscible liquid
      phases system containing surfactants.
AB  - PURPOSE: The extraction of proteins from PLGA/PLA microspheres by a two
      immiscible liquid phases system with the addition of surfactants was
      investigated. METHODS: First, the extraction without surfactants and the
      interaction between proteins (IFN-alpha2b and EGF) and empty microspheres (PLGA
      or PLA) was studied. Next, proteins stability in presence of different
      surfactants was evaluated by: (1) bicinchoninic acid protein assay, (2) reversed
      phase-high performance liquid chromatography, and (3) enzyme-linked immunosorbent
      assay. Then, proteins were extracted with PBS/dichloromethane including selected
      surfactants and characterized by the above mentioned techniques, biological
      activity tests, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and
      electrospray ionization mass spectrometry. RESULTS: Without surfactants, protein
      recovery was only 27-43% for IFN-alpha2b and 58-73% for EGF. Protein content in
      solutions incubated with blank microspheres decreased to 66% for IFN-alpha2b and
      86% for EGF. It was only possible to quantify the EGF and IFN-alpha2b in the same
      manner as in PBS alone when the surfactant added was Pluronic F-68 and SDS,
      respectively. Addition of these surfactants allowed the complete isolation of
      both biomolecules from the microspheres. The extraction procedure did not affect
      the encapsulated proteins. CONCLUSION: Proteins can be quantitatively extracted,
      without changes, from PLGA/PLA microspheres using PBS/dichloromethane system that
      include an appropriate surfactant.

PMID- 23135822
TI  - Intranasal treatment of central nervous system dysfunction in humans.
AB  - One of the most challenging problems facing modern medicine is how to deliver a
      given drug to a specific target at the exclusion of other regions. For example, a
      variety of compounds have beneficial effects within the central nervous system
      (CNS), but unwanted side effects in the periphery. For such compounds,
      traditional oral or intravenous drug delivery fails to provide benefit without
      cost. However, intranasal delivery is emerging as a noninvasive option for
      delivering drugs to the CNS with minimal peripheral exposure. Additionally, this
      method facilitates the delivery of large and/or charged therapeutics, which fail
      to effectively cross the blood-brain barrier (BBB). Thus, for a variety of growth
      factors, hormones, neuropeptides and therapeutics including insulin, oxytocin,
      orexin, and even stem cells, intranasal delivery is emerging as an efficient
      method of administration, and represents a promising therapeutic strategy for the
      treatment of diseases with CNS involvement, such as obesity, Alzheimer's disease,
      Parkinson's disease, Huntington's disease, depression, anxiety, autism spectrum
      disorders, seizures, drug addiction, eating disorders, and stroke.

PMID- 23135824
TI  - Drug delivery characteristics of the progenitor bronchial epithelial cell line
      VA10.
AB  - PURPOSE: To determine the integrity and permeability properties of the
      immortalized human VA10 bronchial epithelial cell line for its suitability as an
      in vitro drug permeation model. METHODS: Cells were grown under liquid-covered
      culture (LCC) or air-liquid interface (ALI) culture, characterized using electron
      microscopy and immunostaining. Integrity was measured using transepithelial
      electrical resistance (TER) and permeability of fluorescein sodium (Flu-Na).
      General permeability was established with dextrans and model drugs and P
      glycoprotein (P-gp) function determined with bidirectional flux of rhodamine-123.
      RESULTS: ALI culture resulted in 2-3 cell layers with differentiation towards
      ciliated cells but LCC showed undifferentiated morphology. VA10 cells formed TJ,
      with higher TER in LCC than ALI (~2500 vs. ~1200 Omega*cm(2)) and Flu-Na
      permeability ~1-2 * 10(-7) cm/s. ALI cultured cells expressed P-gp and
      distinguished between compounds depending on lipophilicity and size, consistent
      with previous data from Calu-3 and 16HBE14o-cell lines. CONCLUSIONS: ALI cultured
      cell layers capture the in vivo-like phenotype of bronchial epithelium and form
      functional cell barrier capable of discriminating between compounds depending on
      physiochemical properties. The VA10 cell line is an important alternative to
      previously published cell lines and a relevant model to study airway drug
      delivery in vitro.

PMID- 23135826
TI  - Optimal management of recurrent prostate cancer in older patients.
AB  - With a large, aging population in the USA and continued prolongation of life
      expectancy, treatment of cancer in the elderly will continue to be of importance.
      The most common cancer in men is prostate cancer, which is most often diagnosed
      in those over the age of 65 years. Initial therapies for prostate cancer are
      local treatments in those with localized disease and for whom definitive therapy
      is appropriate. Optimal treatment of an older patient with recurrent prostate
      cancer now involves more of a decision process than treatment has in the past,
      with the recent approval of several new medical agents for advanced prostate
      cancer. Through this article we will focus on treatment options for recurrent
      prostate cancer, keeping in mind the unique characteristics of the elderly
      population. A majority of the discussion will focus on many of the newly approved
      agents used to treat castration-resistant prostate cancer, and exciting agents
      currently under investigation. Improved androgen blockade has improved overall
      survival in patients with metastatic disease but carries many of the same adverse
      effects as previous agents. Newer approaches with immunotherapy,
      radiopharmaceuticals, or second-generation androgen receptor blockers introduce a
      different adverse-effect profile for older patients. As data matures, these too
      may improve survival for patients with metastatic disease. Throughout all stages
      of disease, one must keep in mind the unique needs of an older patient
      population.

PMID- 23135825
TI  - The impact of glycosylation on the pharmacokinetics of a TNFR2:Fc fusion protein
      expressed in Glycoengineered Pichia Pastoris.
AB  - PURPOSE: P. pastoris has previously been genetically engineered to generate
      strains that are capable of producing mammalian-like glycoforms. Our objective
      was to investigate the correlation between sialic acid content and
      pharmacokinetic properties of recombinant TNFR2:Fc fusion proteins generated in
      glycoengineered P. pastoris strains. METHODS: TNFR2:Fc fusion proteins were
      generated with varying degrees of sialic acid content. The pharmacokinetic
      properties of these proteins were assessed by intravenous and subcutaneous routes
      of administration in rats. The binding of these variants to FcRn were also
      evaluated for possible correlations between in vitro binding and in vivo PK.
      RESULTS: The pharmacokinetic profiles of recombinant TNFR2:Fc produced in P.
      pastoris demonstrated a direct positive correlation between the extent of
      glycoprotein sialylation and in vivo pharmacokinetic properties. Furthermore,
      recombinant TNFR2:Fc produced in glycoengineered Pichia, with a similar sialic
      acid content to CHO-produced etanercept, demonstrated similar in vivo
      pharmacokinetic properties to the commercial material. In vitro surface plasmon
      resonance FcRn binding at pH6.0 showed an inverse relationship between sialic
      acid content and receptor binding affinity, with the higher affinity binders
      having poorer in vivo PK profiles. CONCLUSIONS: Sialic acid content is a critical
      attribute for modulating the pharmacokinetics of recombinant TNFR2:Fc produced in
      glycoengineered P. pastoris.

PMID- 23135827
TI  - The toxic effect of chitosan/metal-impregnated textile to synanthropic mites.
AB  - BACKGROUND: Plasma treatment enables effective binding of chitosan film to
      textile fibres. Heavy metal ions such as Ag(+) adsorbed onto the chitosan coating
      are known to enhance toxicity to microorganisms. The acaricidal effect of
      chitosan and chitosan/metal adducts with Ag(+) , Zn(2+) and Cu(2+) was tested in
      laboratory experiments. Tested species Acarus siro, Dermatophagoides farinae, D.
      pteronyssinus and Tyrophagus putrescentiae are allergen producers and important
      pests in house dust, stored food and feed. The mortality was compared after 24 h
      of exposure of mites to plasma-treated textiles. RESULTS: Chitosan/Ag(+) textile
      caused at least 80% mortality of all species tested. Chitosan/Zn(2+) and
      chitosan/Cu(2+) textiles had a smaller effect on mite mortality than
      chitosan/Ag(+) . The conversion of chitosan/Ag(+) finishing to chitosan/Ag2 O did
      not influence the mortality of mites in biotests, except that of Tyrophagus
      putrescentiae, where the mortality decreased from 86 to 64%. CONCLUSION: The
      results support a great potential of chitosan/Ag(+) fibres in acaricidal
      materials and/or mite protective food packages.

PMID- 23135828
TI  - Temporal techniques: dynamic tracking of nanomaterials in live cells.
AB  - Temporal analytical techniques to track nanoparticles in live cell would provide
      rich information to well understand the biologic properties of nanoparticles in
      molecular level. Significant advances in fluorescence microscopy techniques with
      high temporal and spatial resolution allow single nanoparticles to label
      biomolecules, ions, and microstructures in live cells, which will address many
      fundamental questions in cell biology. This review highlights the real time
      tracking techniques for monitoring the movement of nanomaterials such as carbon
      nanotubes (CNTs), quantum dots (QDs), metal clusters, upconver-sional
      nanomaterials, and polystyrene (PS) nanoparticles etc. in live cells. The
      biological properties of nanoparticles in live cells are also briefly summarized
      according to fluorescence microscopy studies.

PMID- 23135829
TI  - The virucidal effect against murine norovirus and feline calicivirus as
      surrogates for human norovirus by ethanol-based sanitizers.
AB  - This study examined the virucidal effects of five types of alcohol-based
      sanitizers including malic acid and sodium malate, or monoethanolamin, in 58 vol
      % ethanol (pH 4.0, pH 7.1, pH 11.8), 65 vol % ethanol (pH 4.2), and 75 vol %
      ethanol (pH 4.4) against murine norovirus (MNV) and feline calicivirus (FCV). The
      virus titer of MNV was reduced in an ethanol dose-dependent manner under the same
      pH (about 4.0) condition. Virucidal effect against MNV was correlated with pH
      when the concentration of ethanol was constant (58 vol %). All the ethanol-based
      sanitizers provided sufficient virucidal effects against FCV. In conclusion, the
      virucidal effect of the ethanol-based sanitizer at low concentration of ethanol
      against norovirus (NoV) is increased when the pH is adjusted to a neutral state. 

PMID- 23135830
TI  - Prevalence and predictors of post-traumatic stress symptoms in adolescent and
      young adult cancer survivors: a 1-year follow-up study.
AB  - OBJECTIVES: Post-traumatic stress symptoms (PTSS) have been identified as a
      meaningful indicator of distress in cancer survivors. Distinct from young adult
      survivors of childhood cancer, young people diagnosed with cancer as adolescents
      and young adults (AYAs) face unique psychosocial issues; however, there is little
      published research of PTSS in the AYA population. This study examines prevalence
      and predictors of PTSS among AYAs with cancer. METHODS: As part of a longitudinal
      study of AYAs with cancer, 151 patients aged 15-39 years completed mailed surveys
      at 6 and 12 months post-diagnosis. Severity of PTSS was estimated at 6 and 12
      months post-diagnosis. Multiple regression analyses were conducted to investigate
      the predictive effects of socio-demographic and clinical characteristics on
      changes in PTSS over time. RESULTS: At 6 and 12 months, respectively, 39% and 44%
      of participants reported moderate to severe levels of PTSS; 29% had PTSS levels
      suggestive of post-traumatic stress disorder. No significant differences in
      severity of PTSS between 6 and 12 months were observed. Regression analyses
      suggested that a greater number of side effects were associated with higher
      levels of PTSS at 6 months. Currently receiving treatment, having surgical
      treatment, diagnosis of a cancer type with a 90-100% survival rate, remaining
      unemployed/not in school, and greater PTSS at 6 months were associated with
      higher levels of PTSS at 12 months. CONCLUSIONS: Post-traumatic stress symptoms
      were observed as early as 6 months following diagnosis and remained stable at 12
      month follow-up. The development of early interventions for reducing distress
      among AYA patients in treatment is recommended.

PMID- 23135831
TI  - The relation between social cohesion and smoking cessation among Black smokers,
      and the potential role of psychosocial mediators.
AB  - BACKGROUND: Social cohesion, the self-reported trust and connectedness between
      neighbors, may affect health behaviors via psychosocial mechanisms. PURPOSE:
      Relations between individual perceptions of social cohesion and smoking cessation
      were examined among 397 Black treatment-seeking smokers. METHODS: Continuation
      ratio logit models examined the relation of social cohesion and biochemically
      verified continuous smoking abstinence through 6 months post-quit. Indirect
      effects were examined in single mediator models using a nonparametric
      bootstrapping procedure. All analyses controlled for sociodemographics, tobacco
      dependence, and treatment. RESULTS: The total effect of social cohesion on
      continuous abstinence was non-significant (beta = 0.05, p = 0.10). However,
      social cohesion was associated with social support, positive affect, negative
      affect, and stress, which, in turn, were each associated with abstinence in
      adjusted models (ps < 0.05). CONCLUSIONS: Results suggest that social cohesion
      may facilitate smoking cessation among Black smokers through desirable effects on
      psychosocial mechanisms that can result from living in a community with strong
      interpersonal connections.

PMID- 23135832
TI  - Triblock copolymer-based microchip device for rapid analysis of stuffer-free
      multiplex ligation-dependent probe amplification products.
AB  - Recent improvements in the multiplex ligation-dependent probe amplification
      (MLPA) method promise successful multiplex analysis of various genetic markers.
      In particular, it has been demonstrated that elimination of the stuffer sequence
      included in MLPA probes for length-dependent analysis substantially simplifies
      the probe design process and improves the accuracy of the analysis. As is the
      case for other CE-based methods, MLPA could be further developed on a microchip
      platform. However, high-resolution analysis of short MLPA probes requires careful
      microchip operation. In this study, we developed a microchip device for the
      multiplex analysis of five food-borne pathogens using a stuffer-free probe set.
      Microchip channel design and electrophoresis operating conditions were first
      optimized for reproducible analysis, after which two sieving matrices were
      tested. Finally, the method was validated using DNA samples isolated from
      intentionally infected milk.

PMID- 23135833
TI  - A conversation with professor Newton Ennis Morton.

PMID- 23135834
TI  - 'Getting things done': an everyday-life perspective towards bridging the gap
      between intentions and practices in health-related behavior.
AB  - In this paper, we aim to add a new perspective to supporting health-related
      behavior. We use the everyday-life view to point at the need to focus on the
      social and practical organization of the concerned behavior. Where most current
      approaches act disjointedly on clients and the social and physical context, we
      take the clients' own behavior within the dynamics of everyday context as the
      point of departure. From this point, healthy behavior is not a distinguishable
      action, but a chain of activities, often embedded in other social practices.
      Therefore, changing behavior means changing the social system in which one lives,
      changing a shared lifestyle or changing the dominant values or existing norms.
      Often, clients experience that this is not that easy. From the everyday-life
      perspective, the basic strategy is to support the client, who already has a
      positive intention, to 'get things done'. This strategy might be applied to those
      cases, where a gap is found between good intentions and bad behavior. 

PMID- 23135835
TI  - Adherence to clinical guidelines in management of diabetes and prevention of
      cardiovascular disease in Qatar.
AB  - INTRODUCTION: The prevalence of diabetes mellitus (DM) in the UK increased in
      2009 to 4 %, of which type-2 diabetes accounts for 85-95 % of all cases. In Qatar
      the prevalence of DM among the adult Qatari population in 2008 was 16.7 %; around
      four times higher than the prevalence in the UK. The aim of the study was to
      design and to apply a medication assessment tool (MAT) to determine the level of
      adherence to internationally recognised guideline recommendations in type-2
      diabetes management and in primary prevention of cardiovascular disease (CVD)
      among type-2 diabetes patients, to quantify any gaps in guideline implementation.
      MATERIALS AND METHODS: 305 patients were included in this study; all diagnosed
      with type-2 diabetes with no history of CVD. A 38 criteria MAT was designed from
      published guideline recommendations on the management of type-2 diabetes and
      combined with recommendations relevant to primary prevention of cardiovascular
      disease. The MAT comprised 21 criteria assessing control of blood glucose, 5
      criteria assessing management of diabetes complications and 12 criteria assessing
      preventive medication use in CVD. The MAT was validated by a group of
      practitioners and researchers and field tested in the diabetes outpatient clinic
      within Hamad General Hospital, Qatar, with electronic and manual access to
      patients' medical records. Levels of applicability and adherence to each
      criterion were calculated individually and the overall adherence was determined.
      RESULTS: The MAT was applied to the whole study sample (11,590 assessed criteria
      in 305 patients). Application of the MAT identified 19/38 criteria with high
      levels of adherence (>=80 %), 9/38 criteria with intermediate levels of adherence
      (>=50 %; <80 %) and 10/38 criteria with low levels of adherence (<50 %). The
      overall adherence in 305 patients was 68.1 % (95 % CI: 67, 69) in 6,657
      applicable criteria. Total non-adherences, both justified and unjustified, were
      found in 30.8 % (95 % CI: 30, 32) in 2,049 of the applicable criteria in which
      only 5.8 % (95 % CI: 5, 7) in 118 criteria had a documented justification.
      Consequently 94.2 % of all non-adherences (95 % CI: 93, 95) in 1,931 criteria had
      unjustified non-adherence and indicated a need for inclusion in treatment review
      through an appropriate pharmaceutical care plan. DISCUSSION AND CONCLUSION: The
      study identifies levels of adherence to guideline recommendations, the need for
      additional documentation and criteria with low adherence that might be a focus
      for an educational intervention and a starting point for targeted pharmaceutical
      care.

PMID- 23135836
TI  - An audit of prophylactic surgical antibiotic use in a Sudanese Teaching Hospital.
AB  - BACKGROUND: Antibiotic prophylaxis is effective at reducing the risk of
      postoperative infection for nearly all types of surgery. Objective To audit the
      use of prophylactic antibiotics for elective surgery. SETTING: Khartoum Teaching
      Hospital, Sudan, a 1,000 bed tertiary level hospital. METHOD: A prospective study
      was conducted over a 9 month period; patients admitted for elective surgery were
      included consecutively. MAIN OUTCOME MEASURE: The use and administration of
      prophylactic antibiotics for elective surgery. RESULTS: A total of 1,768 patients
      with mean age 37.8 +/- 14 years were recruited (females, 83.3 % of total) who
      underwent 1,814 surgical interventions. Of these 1,277 (70.4 %) of procedures
      were clean-contaminated. A total of 1,758 patients (99.4 % of total) received
      antibiotics for prophylaxis; 1,730 patients (97.9 %) were given antibiotics in
      the operating room; for 1,288 (74.5 %) of cases the antibiotics were considered
      'recommended', while for 442 (25.5 %) they were not. Out of the patients for whom
      prophylaxis was recommended and was given, 725 (56.3 %) of patients received a
      broad spectrum antibiotic or unnecessary combination, 913 (70.9 %) received a sub
      therapeutic dose, 120 (9.3 %) were given the first preoperative dose within the
      proper time window, and 1,250 (97 %) of patients had an extended duration of
      prophylaxis. Compliance with all stated criteria was achieved in only 47 (2.7 %)
      of observed prescriptions. CONCLUSION: This audit showed a wide gap between
      international standards and local practices; the authors call for urgent action
      to correct this situation through the development and implementation of local
      clinical guidelines.

PMID- 23135837
TI  - The surgical management of active ulcerative colitis complicated by Clostridium
      difficile infection.
AB  - INTRODUCTION: Clostridium difficile stool toxin is detected in 5-20 % of patients
      with acute exacerbations of ulcerative colitis (UC). There is little data
      regarding the safety of surgery for UC with concurrent C. difficile. METHODS: A
      retrospective review was performed of 23 patients undergoing colectomy for
      refractory UC complicated by C. difficile infection between January 2002 and June
      2012. Patients were stratified into those who completed a full antibiotic course
      for C. difficile infection prior to surgery (group A, n = 7) and those who
      proceeded directly to surgery (group B, n = 16). The primary endpoints of
      perioperative mortality, ICU requirement, reoperation, readmission, and surgical
      site infection were assessed within 30 days after surgery. RESULTS:
      Postoperatively, no mortalities, ICU admissions, readmission, or reoperations
      occurred. One group A patient developed a superficial wound infection, which
      resolved with a course of outpatient antibiotics (14 vs. 0 %, p = 0.12). Average
      days until return of bowel function and average length of postoperative stay were
      comparable between group A and B (3.9 vs. 3.6 days, p = 0.70; 7.0 vs. 6.9 days, p
      = 0.87; respectively). Ninety-one percent of patients subsequently underwent
      ileal pouch-anal anastomosis. CONCLUSION: Colectomy for ulcerative colitis
      complicated by C. difficile can be performed safely without completing a course
      of antibiotic therapy.

PMID- 23135838
TI  - Investigation of the substrate range of CYP199A4: modification of the partition
      between hydroxylation and desaturation activities by substrate and protein
      engineering.
AB  - The cytochrome P450 enzyme CYP199A4, from Rhodopseudomonas palustris HaA2, can
      efficiently demethylate 4-methoxybenzoic acid. It is also capable of oxidising a
      range of other related substrates. By investigating substrates with different
      substituents and ring systems we have been able to show that the carboxylate
      group and the nature of the ring system and the substituent are all important for
      optimal substrate binding and activity. The structures of the veratric acid, 2
      naphthoic acid and indole-6-carboxylic acid substrate-bound CYP199A4 complexes
      reveal the substrate binding modes and the side-chain conformational changes of
      the active site residues to accommodate these larger substrates. They also
      provide a rationale for the selectivity of product oxidation. The oxidation of
      alkyl substituted benzoic acids by CYP199A4 is more complex, with desaturation
      reactions competing with hydroxylation activity. The structure of 4-ethylbenzoic
      acid-bound CYP199A4 revealed that the substrate is held in a similar position to
      4-methoxybenzoic acid, and that the C(beta) C-H bonds of the ethyl group are
      closer to the heme iron than those of the C(alpha) (3.5 vs. 4.8 A). This
      observation, when coupled to the relative energies of the reaction intermediates,
      indicates that the positioning of the alkyl group relative to the heme iron may
      be critical in determining the amount of desaturation that is observed. By
      mutating a single residue in the active site of CYP199A4 (Phe185) we were able to
      convert the enzyme into a 4-ethylbenzoic acid desaturase.

PMID- 23135839
TI  - Regioselective C-H alkylation of anisoles with olefins catalyzed by cationic half
      sandwich rare earth alkyl complexes.

PMID- 23135840
TI  - Rice artificial hybridization for genetic analysis.
AB  - Artificial hybridization has probably been practiced since ancient time; however,
      the science of genetics did not initiate until Gregor Mendel conducted a series
      of crosses between different pure lines of garden pea and made careful
      observations and systematical analyses of their offspring. Artificial
      hybridization or crossing between carefully chosen parents has been and still is
      the primary way to transfer genes from different germplasm for self-pollinated
      rice. Through gene recombination, novel genetic variation is created by different
      arrangements of genes existing in parental lines. Procedures of artificial
      hybridization involve the selection of appropriate panicles from representative
      plants of the female parents, the emasculation of female parents, and the
      pollination of emasculated panicles with abundant pollens of selected male
      parents. Of the numerous proposed methods, hot water and vacuum emasculation have
      proven to be the most robust and reliable ones. A successful and efficient
      hybridization program also relies on the knowledge of parental lines or
      germplasm, the reproductive biology and development of rice, the conditions
      needed to promote flowering and seed development, and the techniques to
      synchronize flowering of diverse parents.

PMID- 23135841
TI  - Fluorescence in situ hybridization techniques for cytogenetic and genomic
      analyses.
AB  - Fluorescent in situ hybridization (FISH) is a powerful method to visualize DNA
      sequences in the context of the whole chromosome. Yet despite the value of FISH
      analysis for cytogenetic studies, there are surprisingly few labs that are able
      to adapt the technique for their experiments in chromosomal and genome biology.
      Here we present a comprehensive FISH protocol acquired from over 20 years of
      collective experience using different plant species. Our description uses rice as
      a model for performing a complete FISH procedure, but the protocol can be readily
      adapted for other plant species. We have provided more specialized instruction
      beyond routine FISH, which includes the preparation of meiotic and mitotic
      samples suitable for FISH analysis, procedures for direct and indirect labeling
      of DNA probes, and techniques for increasing signal strength using layers of
      antibodies.

PMID- 23135842
TI  - Generation of rice mutants by chemical mutagenesis.
AB  - Chemical mutagenesis of rice has been used extensively to generate useful genetic
      variation for the purpose of breeding improved varieties. More recently, advances
      in high-throughput genotyping platforms have enabled the efficient detection of
      point mutations generated by chemical agents. This in turn has renewed interest
      in using traditional chemical mutagenesis to generate mutant populations for gene
      discovery and functional characterization. Targeting of Induced Local Lesions in
      Genomes (TILLING) is a powerful reverse genetics method which combines chemical
      mutagenesis with the high-throughput discovery of point mutations. Numerous
      chemical mutagens have been shown to be effective in generating point mutations
      and small deletions in rice. This chapter describes the use of a combination of
      sodium azide (NaN(3)) and N-nitroso-N-methylurea to generate populations that are
      suitable for TILLING as well as forward genetics and mutation breeding.

PMID- 23135843
TI  - TILLING and ecotilling for rice.
AB  - Mutagenesis is frequently used to test gene function and to aid in crop
      improvement. Targeting Induced Local Lesions in Genomes (TILLING) is a reverse
      genetic strategy first developed to identify induced point mutations in
      Arabidopsis. This general strategy has since been applied to many plant and
      animal species. Here, we describe a protocol for high-throughput TILLING in rice.
      Gene segments are amplified using fluorescently tagged primers, and products are
      denatured and reannealed to form heteroduplexes between the mutated and wild-type
      sequences. These heteroduplexes are substrates for cleavage by single-strand
      specific nucleases. Following cleavage, products are analyzed on denaturing
      polyacrylamide gels using the LI-COR DNA analyzer system. Several rice TILLING
      populations have been described, and a public mutation screening service is now
      available. The basic methods used for TILLING can be adapted for the discovery
      and cataloguing of natural nucleotide variation in populations, a strategy known
      as Ecotilling, which was first used to study genetic diversity among Arabidopsis
      ecotypes, and has since been applied to crop plants.

PMID- 23135844
TI  - Functional characterization of rice genes using a gene-indexed T-DNA insertional
      mutant population.
AB  - Despite the availability of the finished genome sequence and tools for its
      analyses, few rice genes have been characterized. Because Agrobacterium-mediated
      transformation causes random T-DNA insertions across the genome, T-DNA can be a
      good mutagen for functional genomics. Gene-indexed mutants with flanking
      sequences around inserted T-DNA are valuable resources for accelerating
      functional characterizations of rice genes. Such mutant lines, covering at least
      half the rice genome, have been generated through international efforts. Here, we
      describe approaches that use functional genomics with T-DNA insertional
      mutagenesis.

PMID- 23135845
TI  - QTL analysis and map-based cloning of salt tolerance gene in rice.
AB  - Most agronomic traits are governed by quantitative trait loci (QTLs) and exhibit
      continuous distribution in a segregating population. The hereditary
      characteristics of these traits are more complicated than those of monogenic
      traits. Detection and isolation of these QTLs can greatly improve crop production
      throughout the world. In recent times, significant progress has been made toward
      understanding the molecular basis underlying quantitative traits. Herein, we
      describe a QTL-mapping protocol for detecting and cloning a major QTL regulating
      rice shoot K(+) concentration under salt stress conditions. This QTL-mapping
      approach combined with the marker-assisted selection technique can be applied for
      the elucidation of complex traits in rice and other cereal crops.

PMID- 23135846
TI  - Site-specific gene integration in rice.
AB  - Site-specific gene integration is a powerful technique for ensuring stable
      transgene expression. Transgenic plants produced by conventional transformation
      techniques often display highly variable transgene expression, which is mostly
      attributed to integration patterns consisting of multiple copies of transgene
      constructs. Therefore, it is desirable to generate single-copy integrations,
      preferably in a characterized genomic position. Precise integration of foreign
      genes into a selected genomic position can be obtained by employing site-specific
      recombination systems derived from bacteria or yeast. P1 bacteriophage Cre-lox
      system has been particularly successful in directing precise integration of
      foreign genes into "previously engineered" genomic sites. The resulting
      transgenic plants display stable expression through successive generations.
      Therefore, site-specific integration approach is useful for streamlining
      production of transgenic plants.

PMID- 23135847
TI  - Transcriptome profiling analysis using rice oligonucleotide microarrays.
AB  - Transcriptome analysis using oligonucleotide microarrays is a powerful tool for
      detecting changes in genome-wide transcripts under a given biological condition.
      Although the rice genome sequence is available, the number of functionally
      characterized genes in rice is still very limited. Genome-wide transcriptome
      analysis is a useful tool for elucidating the functions of rice genes that have
      not yet been determined. Currently, more than 3,000 arrays are publicly
      available. Here, we introduce methods for genome-wide transcriptome analysis in
      rice.

PMID- 23135848
TI  - Cloning of small RNAs for the discovery of novel microRNAs in plants.
AB  - Endogenous small RNAs can be grouped into several distinct classes of 21-nt-long
      microRNAs (miRNAs), short interfering RNAs (siRNAs), trans-acting siRNAs
      (tasiRNAs), and 24-nt long heterochromatic siRNAs. miRNAs are increasingly being
      recognized as significant effectors of gene regulation in a wide range of
      organisms. These molecules are typically ~21-nt long and are amenable for cloning
      by streamlined protocols. Here we detail the methodology for cloning small RNAs
      in rice to identify novel miRNAs and other important small RNAs. Briefly, small
      RNA molecules are size fractionated, attached to adaptors, and subsequently
      converted into cDNA and PCR amplified. Current high-throughput sequencing
      technologies allow sequencing of the PCR products directly.

PMID- 23135849
TI  - Global identification of small RNA targets in plants by sequencing sliced ends of
      messenger RNAs.
AB  - Small RNAs (microRNAs and other classes of endogenous small interfering RNAs)
      play important roles in a wide variety of biological processes. However,
      integration of small RNAs in diverse biological networks relies on the
      confirmation of their RNA targets. In plants, miRNAs negatively regulate mRNA
      targets by guiding a cleavage in the complementary site that leaves a 3'
      polyadenylated RNA possessing monophosphate at its 5' end. This chapter describes
      a detailed step-by-step protocol for cloning such sliced 3' products in order to
      identify small RNA targets. Using this protocol, we have identified more than 150
      small RNA targets in rice; some are conserved and others are non-conserved
      targets for rice small RNAs.

PMID- 23135850
TI  - Artificial microRNAs for specific gene silencing in rice.
AB  - Artificial microRNAs (amiRNAs) have been shown to facilitate efficient gene
      silencing with high specificity to the intended target gene(s). For the plant
      breeder, gene silencing by artificial miRNAs will certainly accelerate gene
      discovery, because it allows targeting of all genes in a mapping interval,
      independent of the genetic background. In addition, beneficial knockout
      phenotypes can easily be transferred between varieties and across incompatibility
      barriers. This chapter describes the generation and application of amiRNAs as a
      gene silencing tool in rice.

PMID- 23135851
TI  - Rice proteomic analysis: sample preparation for protein identification.
AB  - Rice is one of the most important food and cereal crop plants in the world. Rice
      proteomics began in the 1990s. Since then, considerable progress has been made in
      establishing protocols from isolation of rice proteins from different tissues,
      organs, and organelles, to separation of complex proteins and to their
      identification by mass spectrometry. Since the year 2000, global proteomics
      studies have been performed during growth and development under numerous biotic
      and abiotic environmental conditions. Two-dimensional (2-D) gel-based proteomics
      platform coupled with mass spectrometry has been retained as the workhorse for
      proteomics of a variety of rice samples. In this chapter, we describe in detail
      the different protocols used for isolation of rice proteins, their separation,
      detection, and identification using gel-based proteomics and mass spectrometry
      approaches.

PMID- 23135852
TI  - Quantification of jasmonic and salicylic acids in rice seedling leaves.
AB  - Jasmonic acid (JA) and salicylic acid (SA) are critical signaling components
      involved in various aspects of plant growth, development, and defense. Their
      constitutive levels vary from plant to plant and also from tissue to tissue
      within the same plant. Moreover, their quantitative levels change when plant is
      exposed to biotic and abiotic stresses. To better understand the JA- and SA
      mediated signaling and metabolic pathways, it is important to precisely quantify
      their levels in plants/tissues/organs. However, their extraction and
      quantification are not trivial and still technically challenging. An effort has
      been made in various laboratories to develop a simple and standard procedure that
      can be utilized for quantification of JA and SA. Here, we present the
      experimental procedure and our decade of experience on extracting and quantifying
      them in an absolute manner in leaves of rice seedlings. We must mention that this
      method has been applied to both monocotyledonous and dicotyledonous plants for
      absolute quantification of JA and SA. As collaboration is the key towards rapid
      progress in science and technology, we are always open to sharing our experience
      in this field with any active research group with an aim to improve the procedure
      further and eventually to connect the importance of their (JA and SA)
      quantitative levels with networks of signaling and metabolic pathways in plants.

PMID- 23135853
TI  - Analysis of insect-induced volatiles from rice.
AB  - Plants emit volatile organic compounds (VOCs) from various organs. To understand
      the biological and ecological roles of plant VOCs as well as their biosynthesis,
      it is important to determine the quality and quantity of individual plant VOCs.
      Here we describe three techniques, including solid-phase microextraction, closed
      loop stripping system, and an open dynamic system, for sampling volatiles emitted
      from insect-damaged rice plants. In addition, the protocol for using gas
      chromatography-mass spectrometry to elucidate the chemical identities of rice
      volatiles is described.

PMID- 23135854
TI  - Phenotypic and physiological evaluation for drought and salinity stress responses
      in rice.
AB  - Drought and salinity stresses seriously affect rice plant growth and yield. The
      growing need to improve rice cultivars for drought and salt tolerance requires
      the development of reproducible screening methods that simulate field conditions,
      and which provide quantitative data for statistical testing and selection of
      genotypes with differential responses. In addition, the study of molecular
      responses to drought and salt stress requires controlled conditions for growth
      and treatments that are reportable and comparable between different laboratories.
      Drought, also known as soil water deficit, can result from insufficient moisture
      for a plant to grow adequately and complete its life cycle. Salinity due to
      excess sodium chloride affects rice at seedling and flowering stages, reducing
      root and leaf growth. Both these abiotic stresses can lead to major physiological
      and biochemical changes such as reduced photosynthesis and reprogramming of gene
      expression. The methods presented in this chapter can be applied for (a)
      examination of stress responses in rice vegetative and reproductive tissues to
      identify and characterize molecular and physiological responses; (b) testing of
      candidate genes by overexpression or knockout studies evaluated for altered
      stress response phenotypes; and (c) screening of different genotypes such as
      accessions or segregating populations for their quantitative responses to abiotic
      stress parameters.

PMID- 23135855
TI  - Phenotypic, physiological, and molecular evaluation of rice chilling stress
      response at the vegetative stage.
AB  - Rice is a chilling-sensitive plant that is particularly prone to injury during
      the early stages of seedling development and during flowering. Significant
      variation exists between subspecies with japonica cultivars generally being less
      sensitive than most indica cultivars. In most temperate and subtropical countries
      where rice is grown, crop damage often occurs during the early stages of seedling
      development due to occasional cold snaps coinciding with the first few weeks
      after direct seeding in late spring to early summer. Irreversible injuries often
      result in seedling mortality or if the crop survives a stress episode, plant
      vigor and resistance to pests and diseases are severely compromised. Recent
      physiological and molecular studies have shown that oxidative stress is the
      primary cause of early chilling injuries in rice and the differential responses
      of indica and japonica cultivars are defined to a large extent by gene expression
      related to oxidative signaling and defenses. In this chapter, we summarize basic
      phenotypic, physiological, and molecular procedures that can be adopted for
      routine evaluation of differential responses between cultivars as well as for
      functional genomics studies.

PMID- 23135856
TI  - Analysis of rice root hair morphology using cryo-scanning electron microscopy.
AB  - Root hairs are highly polarized long tubular outgrowths from the surface of
      epidermal trichoblast cells. Root hair development is a simple process that has
      facilitated for the study of cell fate determination and tissue differentiation
      in higher plants. Root hair patterning types in dicot and monocot plants are
      different. Rice is a monocot model plant with type II root hair pattern. The
      method to examine root hair fine structure and cell shape in rice may help
      elucidate the mechanism of cell initiation and differentiation in monocot plants.
      Compared with the critical-point-drying SEM, the Cryo-SEM method has great
      advantage, as the Cryo-SEM can well maintain the delicate structure of root hairs
      in their natural situation. Here we provide the methodology developed to
      investigate several rice mutants with impaired root hair cells using Cryo-SEM.

PMID- 23135857
TI  - Inoculation and virulence assay for bacterial blight and bacterial leaf streak of
      rice.
AB  - Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas oryzae pv. oryzicola (Xoc)
      cause bacterial blight and bacterial leaf streak in rice, respectively. Despite
      being very closely related, the pathogens colonize different tissues and cause
      distinct diseases. The diseases are economically important and also serve as
      model systems for studying plant-bacterial interactions. Here we describe
      protocols for Xoo and Xoc inoculation and disease scoring methods that are
      appropriate to their different modes of infection. These methods are routinely
      used to evaluate pathogen virulence or host responses under controlled
      environmental conditions.

PMID- 23135858
TI  - Inoculation and scoring methods for rice sheath blight disease.
AB  - Sheath blight disease of rice caused by the soilborne fungal pathogen Rhizoctonia
      solani has been a major disease of rice with a serious threat to stable rice
      production worldwide. Although various cultural practices have been used to
      manage the disease, it is advantageous and important to screen rice germplasm and
      identify resistant rice cultivars for more effective disease control. Recent
      advances in methods for the fungal inoculation and disease evaluation have
      enabled a better measurement of host resistance by minimizing confounding factors
      from plant architectures and environmental conditions. This chapter introduces
      five such methods: (1) detached leaf method; (2) micro-chamber method; (3) mist
      chamber method; (4) parafilm sachet method; and (5) aluminum foil method. These
      methods are useful for screening and evaluating disease reactions of rice
      germplasm and facilitating the genetic mapping of disease resistance genes.

PMID- 23135859
TI  - Molecular approaches to improve rice abiotic stress tolerance.
AB  - Abiotic stress is a major factor limiting productivity of rice crops in large
      areas of the world. Because plants cannot avoid abiotic stress by moving, they
      have acquired various mechanisms for stress tolerance in the course of their
      evolution. Enhancing or introducing such mechanisms in rice is one effective way
      to develop stress-tolerant cultivars. Based on physiological studies on stress
      responses, recent progress in plant molecular biology has enabled discovery of
      many genes involved in stress tolerance. These genes include regulatory genes,
      which regulate stress response (e.g., transcription factors and protein kinases),
      and functional genes, which protect the cell (e.g., enzymes for generating
      protective metabolites and proteins). Both kinds of genes are used to increase
      stress tolerance in rice. In addition, several quantitative trait loci (QTLs)
      associated with higher stress tolerance have been cloned, contributing to the
      discovery of significantly important genes for stress tolerance.

PMID- 23135860
TI  - Molecular strategies to improve rice disease resistance.
AB  - Rice diseases such as blast (Magnaporthe oryzae), sheath blight (Rhizoctonia
      solani) and bacterial blight (Xanthomonas oryzae pv oryzae) are a major obstacle
      to achieving optimal yields. To complement conventional breeding method,
      molecular and transgenic method represents an increasingly important approach for
      genetic improvement of disease resistance and reduction of pesticide usage.
      During the past two decades, a wide variety of genes and mechanisms involved in
      rice defense response have been identified and elucidated. These include
      components of pathogen recognition, signal transduction, downstream defense
      related proteins, and crosstalk among different signaling pathways. In addition,
      various molecular strategies including use of specialized promoters, modification
      of target protein structures have been studied and proposed to improve the
      effectiveness of transgenes. While genetically improving rice for enhanced
      disease resistance, it is important to consider potential effects of the
      transgene on rice yield, tolerance to abiotic stresses, and defense against other
      pathogens.

PMID- 23135861
TI  - Molecular strategies to engineer transgenic rice seed compartments for large
      scale production of plant-made pharmaceuticals.
AB  - The use of plants as bioreactors for the large-scale production of recombinant
      proteins has emerged as an exciting area of research. The current shortages in
      protein therapeutics due to the capacity and economic bottlenecks faced with
      modern protein production platforms (microbial, yeast, mammalian) has driven
      considerable attention towards molecular pharming. Utilizing plants for the large
      scale production of recombinant proteins is estimated to be 2-10% the cost of
      microbial platforms, and up to 1,000-fold more cost effective than mammalian
      platforms (Twyman et al. Trends Biotechnol 21:570-578, 2003; Sharma and Sharma,
      Biotechnol Adv 27:811-832, 2009). In order to achieve an economically feasible
      plant production host, protein expression and accumulation must be optimized. The
      seed, and more specifically the rice seed has emerged as an ideal candidate in
      molecular pharming due to its low protease activity, low water content, stable
      protein storage environment, relatively high biomass, and the molecular tools
      available for manipulation (Lau and Sun, Biotechnol Adv 27:1015-1022, 2009).

PMID- 23135862
TI  - A nationwide study of mass urine screening tests on Korean school children and
      implications for chronic kidney disease management.
AB  - BACKGROUND: Since 1998, urine screening tests have been performed on school
      children in Korea. We report the findings of the screening program that analyzed
      patients with proteinuria and/or hematuria. METHODS: Between 1999 and 2008, 5,114
      children were referred to pediatric nephrologists at seven nationwide hospitals.
      Renal biopsies were performed on 1,478 children [28.79 % of total subjects; 26.77
      % for isolated hematuria (IH), 9.09 % for isolated proteinuria (IP), and 51.19 %
      for combined hematuria and proteinuria (CHP)] who showed abnormal renal function,
      persistent hematuria and/or proteinuria for more than 6 months, nephrotic-range
      proteinuria, or those with underlying systemic diseases. RESULTS: Chronic
      glomerulonephritis (GN) was detected in 25 % of all visiting subjects. The most
      common findings in renal biopsies were immunoglobulin A (IgA) nephropathy in
      38.97 %, mesangial proliferative GN in 24.29 %, and thin basement membrane
      nephropathy in 13.13 %. Compared with the relative frequency of renal diseases
      associated with urinary abnormalities, CHP (46.90 %) and nephrotic-range
      proteinuria (69.96 %) groups had more frequent GN than the others. Abnormal
      findings on renal ultrasound with or without Doppler scan were noted in 462 cases
      (suspected nutcracker phenomenon, 159; increased parenchymal echogenicity, 92;
      hydronephrosis, 75; simple cyst, 47). CONCLUSION: Mass urine screening tests
      could detect asymptomatic GN in its early stages. Initial aggressive diagnosis
      and treatment for CHP and nephrotic-range groups may prove helpful as
      interventions that delay chronic kidney disease progression. These findings may
      assist in the development of diagnostic and management guidelines for relatively
      mild urinary abnormalities, such as IH or low-grade IP.

PMID- 23135863
TI  - The coming age of geriatric nephrology.

PMID- 23135864
TI  - KIM-1 expression predicts renal outcomes in IgA nephropathy.
AB  - BACKGROUND: Kidney injury molecule-1 (KIM-1) is a sensitive biomarker for
      proximal tubular injury. Recently, a few studies have shown that urinary KIM-1
      has clinical implications in IgA nephropathy (IgAN). We performed this study to
      determine whether tissue KIM-1 has clinical implications for predicting long-term
      outcome and whether urinary KIM-1 is correlated with tissue KIM-1 and kidney
      injury in IgAN patients. METHODS: We assessed the prognostic prediction
      capability of tissue KIM-1 expression in 69 adult patients with IgAN
      retrospectively. Renal biopsies from all patients were scored by a pathologist
      who was blinded to the clinical data for the pathologic variables. The primary
      outcome was the composite of a 50 % reduction in eGFR or end-stage renal disease.
      Tissue KIM-1 expression was assessed semiquantitatively by counting the stained
      tubules per 100* power field; 0 tubule indicates grade 0; 1-5 tubules, grade 1; 6
      10 tubules, grade 2; and more than 10 tubules, grade 3. Comparing urinary KIM-1
      and tissue KIM-1 expression, 50 consecutive IgAN patients were prospectively
      enrolled to measure urinary KIM-1 levels and examine their biopsy specimens by
      KIM-1 immunohistochemistry. RESULTS: Univariate analysis showed that tissue KIM-1
      expression was associated with the renal outcome in IgAN. Multivariate regression
      analysis, as the relationship of tissue KIM-1 with prognosis, was consistent.
      Proteinuria at biopsy and tissue KIM-1 grade 3 were shown to have a prognostic
      value. The concentration of urinary KIM-1/Cr in patients with IgAN was
      significantly higher than that in the normal controls. CONCLUSION: Tissue KIM-1
      expression is an independent predictor of adverse renal outcomes in IgA
      nephropathy patients.

PMID- 23135865
TI  - New strategy for the treatment of type 2 diabetes mellitus with incretin-based
      therapy.
AB  - Incretin-based therapy was first made available for the treatment of type 2
      diabetes mellitus (T2DM) in the US in 2006 and in Japan in 2009. Four DPP-4
      inhibitors and two GLP-1 analog/receptor agonists are currently available. The
      effects of incretin-based therapy are assumed to be exerted mainly through the
      hormonal and neuronal actions of one of the incretins, GLP-1, which is secreted
      from L cells localized in the small intestine. The benefits of this therapy over
      conventional sulfonylureas or insulin injections, such as fewer hypoglycemic
      events and reduced body weight gain, derive from the glucose-dependent
      insulinotropic effect. The protective effects of this therapy on vulnerable
      pancreatic beta-cells and against micro/macroangiopathy in T2DM are also most
      welcome. Indications and/or contraindications for incretin-based therapy should
      be clarified by prospectively studying the experiences of Japanese T2DM patients
      undergoing this therapy in the clinical setting.

PMID- 23135866
TI  - Clinical features and long-term renal outcomes of Japanese patients with obesity
      related glomerulopathy.
AB  - BACKGROUND: Studies have suggested that obesity-related glomerulopathy (ORG) is
      one of the important disease entities leading to end-stage renal disease.
      However, information is limited regarding the clinical features and renal
      outcomes of Japanese ORG patients. METHODS: Among the patients whose renal biopsy
      was performed at our institute during the past 10 years, we identified 28 ORG
      patients. Among them, the renal prognosis of the 20 patients with more than 2
      years of follow-up was further analyzed. The clinical features at biopsy and the
      renal outcomes were compared with those of other ORG cohorts. RESULTS: The
      average values at diagnosis were a body mass index of 32.0 kg/m(2), eGFR of 65
      ml/min/1.73 m(2), and urinary protein excretion of 1.7 g/day. These features were
      less serious than those of the US cohort or the Spanish cohort and were
      compatible with those of the Chinese cohort. At the last observation, seven
      patients (35%) showed a 50% increase in their serum creatinine, and two patients
      (10%) had a 100% increase in serum creatinine and/or end-stage renal disease (end
      point). A multivariate analysis identified the time-averaged proteinuria during
      follow-up as an independent factor that was associated with the slope of renal
      function. The annual rate of patients reaching the end point in the US cohort,
      the Spanish cohort and the current cohort were 6.7, 6.9 and 1.6% per year,
      respectively. CONCLUSION: The long-term outcomes of Japanese ORG patients include
      progression to renal failure, emphasizing the importance of an accurate early
      diagnosis of this entity.

PMID- 23135867
TI  - A girl with difficult lupus nephritis: lupus vasculopathy.
AB  - Lupus vasculopathy (LV) is one of the complications of lupus nephritis. No
      definite therapy has been recommended for the management of LV, and patient
      outcomes are variable. We present the case of a 16-year-old girl who recovered
      from stage V chronic kidney disease due to lupus nephritis with vasculopathy with
      active treatment including pulse methylprednisolone, cyclophosphamide, rituximab
      and plasma exchange.

PMID- 23135869
TI  - Commercial activities and the promotion of health in schools.
AB  - Many companies nowadays consider schools to be an important setting for marketing
      to children. However, important concerns can be raised from a health promotion
      perspective about the potential negative impact of commercial activities on the
      health and well-being of pupils. As this discussion paper will demonstrate, some
      commercial activities raise concerns in relation to physical health and obesity,
      not only by potentially undermining formal curriculum messages, but also through
      the active promotion of specific products, particularly those high in fat, sugar
      or salt. Nonetheless, the issues raised by commercial activities are not solely
      limited to effects on physical health. By allowing commercial activities, schools
      risk instilling in pupils consumer-orientated values. This is significant as such
      values have been linked to the development of poor health and well-being.
      Furthermore, the presence in schools of commercial activities will also militate
      against informed decision-making and be disempowering. There is also evidence
      that business-sponsored teaching materials can contain biased and misleading
      information. The potential negative impacts of commercial activities are
      inconsistent with goals in relation to the promotion of health and the principles
      of health-promoting schools. 

PMID- 23135868
TI  - Aliskiren reduces home blood pressure and albuminuria in patients with
      hypertensive nephrosclerosis.
AB  - BACKGROUND: The aim of this study was to investigate the antialbuminuric and
      antihypertensive effects of aliskiren by monitoring home blood pressure (BP) in
      comparison with the effects of the angiotensin receptor blocker (ARB) valsartan
      in patients with hypertensive nephrosclerosis and albuminuria. METHODS: We
      conducted an open-label, randomized trial to compare the effects of aliskiren
      with those of valsartan. Patients with BP <150/90 mmHg, an estimated glomerular
      filtration rate of 90-30 mL/min/1.73 m(2), and albuminuria >30 mg/g, despite
      treatment with a 160 mg daily dose of valsartan, were randomly assigned to the
      following two groups: the aliskiren group, who switched from 160 mg/day valsartan
      to 150 mg/day aliskiren, which was later increased to 300 mg/day (n = 20); and
      the valsartan group, who continued with 160 mg/day valsartan (n = 20). RESULTS:
      After 12 weeks of treatment, although there was no significant difference in
      clinic BP between groups, a significant reduction in morning and evening systolic
      BP was observed in the aliskiren group. The decrease in albuminuria in the
      aliskiren group was significantly better than that in the valsartan group, and a
      significant correlation was noted between the change in morning systolic BP and
      the change in albuminuria in the aliskiren group (r = 0.564, P = 0.0084).
      CONCLUSION: We showed that aliskiren treatment leads to a greater reduction in
      albuminuria and home systolic BP values than valsartan in patients with
      nephrosclerosis. We propose that aliskiren therapy should be considered as a
      therapeutic modality to complement ARBs in hypertensive patients with
      nephrosclerosis.

PMID- 23135870
TI  - Cartilage regeneration using zonal chondrocyte subpopulations: a promising
      approach or an overcomplicated strategy?
AB  - Cartilage defects heal imperfectly and osteoarthritic changes develop frequently
      as a result. Although the existence of specific behaviours of chondrocytes
      derived from various depth-related zones in vitro has been known for over 20
      years, only a relatively small body of in vitro studies has been performed with
      zonal chondrocytes and current clinical treatment strategies do not reflect these
      native depth-dependent (zonal) differences. This is surprising since mimicking
      the zonal organization of articular cartilage in neo-tissue by the use of zonal
      chondrocyte subpopulations could enhance the functionality of the graft. Although
      some research groups including our own have made considerable progress in
      tailoring culture conditions using specific growth factors and biomechanical
      loading protocols, we conclude that an optimal regime has not yet been
      determined. Other unmet challenges include the lack of specific zonal cell
      sorting protocols and limited amounts of cells harvested per zone. As a result,
      the engineering of functional tissue has not yet been realized and no long-term
      in vivo studies using zonal chondrocytes have been described. This paper
      critically reviews the research performed to date and outlines our view of the
      potential future significance of zonal chondrocyte populations in regenerative
      approaches for the treatment of cartilage defects. Secondly, we briefly discuss
      the capabilities of additive manufacturing technologies that can not only create
      patient-specific grafts directly from medical imaging data sets but could also
      more accurately reproduce the complex 3D zonal extracellular matrix architecture
      using techniques such as hydrogel-based cell printing.

PMID- 23135871
TI  - Impaired left ventricular function as a predictive factor for mid-term survival
      in octogenarians after primary coronary artery bypass surgery.
AB  - BACKGROUND: The impact of preoperative impaired left ventricular ejection
      fraction (EF) in octogenarians following coronary bypass surgery on short-term
      survival was evaluated in this study. METHODS: A total of 147 octogenarians (mean
      age 82.1 +/- 1.9 years) with coronary artery diseases underwent elective coronary
      artery bypass graft between January 2000 and December 2009. Patients were
      stratified into: Group I (n = 59) with EF >50%, Group II (n = 59) with 50% > EF
      >30% and in Group III (n = 29) with 30% > EF. RESULTS: There was no difference
      among the three groups regarding incidence of COPD, renal failure, congestive
      heart failure, diabetes, and preoperative cerebrovascular events. Postoperative
      atrial fibrillation was the sole independent predictive factor for in-hospital
      mortality (odds ratio (OR), 18.1); this was 8.5% in Group I, 15.3% in Group II
      and 10.3% in Group III. Independent predictive factors for mortality during
      follow up were: decrease of EF during follow-up for more that 5% (OR, 5.2), usage
      of left internal mammary artery as free graft (OR, 18.1), and EF in follow-up
      lower than 40% (OR, 4.8). CONCLUSIONS: The results herein suggest acceptable in
      hospital as well short-term mortality in octogenarians with impaired EF following
      coronary artery bypass grafting (CABG) and are comparable to recent literature
      where the mortality of younger patients was up to 15% and short-term mortality up
      to 40%, respectively. Accordingly, we can also state that in an octogenarian
      cohort with impaired EF, CABG is a viable treatment with acceptable mortality.

PMID- 23135872
TI  - Time-dependent release of growth factors from implant surfaces treated with
      plasma rich in growth factors.
AB  - Plasma rich in growth factors (PRGFs) technology is an autologous platelet-rich
      plasma approach that provides a pool of growth factors and cytokines that have
      been shown to increase tissue regeneration and accelerate dental implant
      osseointegration. In this framework, the spatiotemporal release of growth factors
      and the establishment of a provisional fibrin matrix are likely to be key aspects
      governing the stimulation of the early phases of tissue regeneration around
      implants. We investigated the kinetics of growth factor release at implant
      surfaces functionalized either with PRGFs or platelet-poor plasma and correlated
      the results obtained with the morphology of the resulting interfaces. Our main
      finding is that activation and clot formation favors longer residence times of
      the growth factors at the interfaces studied, probably due to their retention in
      the adsorbed fibrin matrix. The concentration of the platelet-derived growth
      factors above the interfaces becomes negligible after 2-4 days and is
      significantly higher in the case of activated interfaces than in the case of
      nonactivated ones, whereas that of the plasmatic hepatocyte growth factor is
      independent of platelet concentration and activation, and remains significant for
      up to 9 days. Platelet-rich plasma preparations should be activated to permit
      growth factor release and thereby facilitate implant surface osseointegration.

PMID- 23135873
TI  - MFU-4 -- a metal-organic framework for highly effective H(2)/D(2) separation.
AB  - The metal-organic framework, MFU-4, possessing small cavities and apertures, is
      exploited for quantum sieving of hydrogen isotopes. Quantum mechanically, a
      molecule confined in a small cavity shows an increase in effective size depending
      on the particle mass, which leads to a faster deuterium adsorption from a
      H(2)/D(2) isotope mixture.

PMID- 23135874
TI  - Antenatal management and outcomes of gastroschisis in the U.K.
AB  - BACKGROUND: The birth prevalence of gastroschisis is increasing worldwide, yet
      little evidence exists concerning the optimal monitoring strategies after
      diagnosis. The aim of this study was to describe the U.K. prevalence, antenatal
      management and outcomes of affected pregnancies. METHODS: Cases were identified
      throughout the U.K. between October 2006 and September 2007, using three
      different sources. RESULTS: The overall birth prevalence of gastroschisis was 4.2
      cases per 10, 000 total births (95% CI 3.6-4.8). Infants were variably monitored
      with growth scans (90%), umbilical artery Doppler ultrasound (85%),
      cardiotocography (65%) and biophysical profile (27%). Bowel measurements were
      undertaken for only 113 infants (52%). Eighty-nine women (43%) were induced and
      63 (31%) laboured spontaneously. Eleven women (5%) had an elective caesarean
      delivery where the sole indication was fetal gastroschisis. CONCLUSIONS: The
      variability in management and paucity of evidence on antenatal monitoring
      approaches suggests there may be a place for randomised trials of fetal
      surveillance strategies in order to develop the evidence to improve outcomes for
      the at-risk fetus with gastroschisis. This study suggests that case ascertainment
      by regional congenital anomaly registers is high; extension of the coverage of
      these registers to the entire cohort of U.K. births would facilitate ongoing
      surveillance and research.

PMID- 23135875
TI  - WYE-120318, a ring contraction product of methylnaltrexone, and structure
      revision of coniothyrione.
AB  - A contracted ring degradation product, WYE-120318 (compound 2), was discovered
      during the development phase for methylnaltrexone bromide (compound 1) drug
      substance. The compound was isolated by high-performance liquid chromatography
      fractionation, and its structure was determined by spectroscopic data analyses.
      WYE-120318 is formed from methylnaltrexone through a benzyl-benzilic acid type
      rearrangement reaction to yield an alpha-hydroxy-cyclopentanecarboxylic acid
      substructure. The proposed structure and the formation mechanism are confirmed by
      the synthesis of WYE-120318 from methylnaltrexone (compound 1). A similar benzyl
      benzilic acid type rearrangement reaction can be envisioned as the biological
      origin of remisporine A (compound 3), a naturally occurring cyclopentadienyl
      compound that autocatalytically dimerizes to remisporine B (compound 4). The
      structure of remisporine A was deduced from its dimer 4. Coniothyione (compound
      5) can be considered as the first example of a stable natural product bearing the
      remisporine A skeleton. However, the regiochemistry of the chlorosubstitution in
      the coniothyrione structure needs to be revised to compound 6 on the basis of the
      nuclear magnetic resonance data and biogenesis analysis.

PMID- 23135876
TI  - Is fluorine-18-fluorodeoxyglucose positron emission tomography useful in
      monitoring the response to treatment in patients with multiple myeloma?
AB  - Fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) is a useful
      diagnostic tool for the staging of patients with multiple myeloma (MM). The aim
      of this study is to perform a systematic review of the usefulness of FDG-PET or
      PET/CT in monitoring response to treatment in patients with MM. A comprehensive
      computer literature search of the PubMed/MEDLINE, Scopus and Embase databases was
      carried out to identify relevant peer-reviewed articles on the use of FDG-PET or
      PET/CT in monitoring the response to treatment in patients with MM. Ten studies
      described investigations of the role of FDG-PET or PET/CT in monitoring the
      response to treatment in 690 patients with MM or solitary plasmacytoma: six of
      these were conducted prospectively, while four studies were retrospective. These
      articles were retrieved in full-text version and analyzed. Based on these
      findings from the literature, FDG-PET or PET/CT appear to be useful in the
      assessment of treatment response in patients with MM.

PMID- 23135877
TI  - Can parent training alter parent practice and reduce conduct problems in ethnic
      minority children? A randomized controlled trial.
AB  - A randomized prevention study for ethnic minority mothers assessed the
      intervention effects of Parent Management Training-Oregon Model (PMTO) on
      maternal parent practices and child behavior. Ninety-six mothers from Somalia and
      Pakistan and their children aged 3 to 9 years were randomized to PMTO or a wait
      list condition (WLC). Assessments were carried out at the baseline and post
      intervention, using standardized measures and a multi-agent approach. All
      analyses were based on the intention-to-treat principle. Analysis of covariance
      (ANCOVA) showed that PMTO was effective in enhancing parent practices, with a
      decrease in harsh discipline and an increase in positive parenting. Moreover,
      PMTO produced reductions in motherreported child conduct problems. The largest
      effect sizes were found among mothers who attended more than 50 % of the PMTO
      group sessions. Teacher reports showed, however, that there were no significant
      intervention effects on conduct problems and social competence in kindergarten or
      school. The results emphasize the importance and feasibility of offering PMTO to
      ethnic minority families.

PMID- 23135878
TI  - Shuttle-mediated nanoparticle delivery to the blood-brain barrier.
AB  - Many therapeutic drugs are excluded from entering the brain due to their lack of
      transport through the blood-brain barrier (BBB). The development of new
      strategies for enhancing drug delivery to the brain is of great importance in
      diagnostics and therapeutics of central nervous diseases. To overcome this
      problem, a viral fusion peptide (gH625) derived from the glycoprotein gH of
      Herpes simplex virus type 1 is developed, which possesses several advantages
      including high cell translocation potency, absence of toxicity of the peptide
      itself, and the feasibility as an efficient carrier for delivering therapeutics.
      Therefore, it is hypothesized that brain delivery of nanoparticles conjugated
      with gH625 should be efficiently enhanced. The surface of fluorescent aminated
      polystyrene nanoparticles (NPs) is functionalized with gH625 via a covalent
      binding procedure, and the NP uptake mechanism and permeation across in vitro BBB
      models are studied. At early incubation times, the uptake of NPs with gH625 by
      brain endothelial cells is greater than that of the NPs without the peptide, and
      their intracellular motion is mainly characterized by a random walk behavior.
      Most importantly, gH625 peptide decreases NP intracellular accumulation as large
      aggregates and enhances the NP BBB crossing. In summary, these results establish
      that surface functionalization with gH625 may change NP fate by providing a good
      strategy for the design of promising carriers to deliver drugs across the BBB for
      the treatment of brain diseases.

PMID- 23135879
TI  - Design and preparation of platinum-acetylide organogelators containing ethynyl
      pyrene moieties as the main skeleton.
AB  - A series of new platinum-acetylide complexes containing ethynyl-pyrene moieties
      as the main skeleton were synthesized and characterized. The investigation of the
      absorption and emission spectra of these complexes revealed that the extension of
      the molecular size with the introduction of different numbered platinum-acetylide
      fragments can efficiently tune the absorption and emission bands from the UV to
      the longer wavelength region. Moreover, the gelation properties of these
      complexes were investigated by the "stable-to-inversion-of-a-test-tube" method.
      Most newly designed platinum-acetylide compounds presented a stable gel-formation
      property in some of the tested solvents. The morphology of the xerogels was
      investigated by scanning electron microscopy (SEM). Furthermore, the
      concentration- and temperature-dependent absorption and emission properties of
      these complexes were investigated, which support the formation of J-type
      assemblies during the aggregation process. More importantly, it was found that
      the complexes 4 a-C6, 4 a, and 4 a-C18 with four platinum-acetylide fragments
      presented potential applications as luminescent organometallic gels.

PMID- 23135880
TI  - Total synthesis of the tremorgenic indole diterpene paspalinine.

PMID- 23135881
TI  - Influence of additional resection of the gastric fundus on excessive weight loss
      in laparoscopic very very long limb Roux-en-Y gastric bypass.
AB  - Roux-en-Y gastric bypass (RYGB) is the gold standard in bariatric surgery. The
      effect of the procedure is based on restriction, malabsorption and changes in
      hormonal axis. Ghrelin is an important appetite hormone which is produced mainly
      in the gastric fundus. By adding a resection of the gastric fundus, we
      hypothesized that excessive weight loss will be more prominent and the satiety
      feelings less pronounced compared to standard RYGB. A total of 73 patients with
      standard very very long limb (VVLL) RYGB (group A) were compared with 44 patients
      with VVLL RYGB with resection of the fundus (group B). Outcome measures were
      excessive weight loss (EWL), body mass index (BMI), early postoperative
      morbidity, change of co-morbidities, and appetite reduction as assessed by an
      appetite questionnaire over a postoperative period of 24 months. Groups were
      comparable in basic preoperative descriptions. Additional fundus resection did
      not influence EWL (group A 66.1 % vs. group B 70.6 %, p = 0.383) or BMI (group A
      29 kg/m(2) vs. group B 27 kg/m(2), p = 0.199). No significant difference in
      morbidity or change of co-morbidities occurred. The appetite and satiety
      questionnaire showed no difference between group A and group B, respectively.
      Adding a resection of the gastric fundus in RYGB did not alter the clinical
      results, i.e., increased excessive weight loss, decrease of appetite, or increase
      of satiety. The value of removing a part of the ghrelin-producing cells might be
      overestimated.

PMID- 23135882
TI  - Anti-M3 muscarinic acetylcholine receptor antibodies in patients with Sjogren's
      syndrome.
AB  - Sjogren's syndrome (SS) is an autoimmune disease that affects exocrine glands
      including salivary and lacrimal glands. Recently, autoantibodies against
      muscarinic acetylcholine receptor M3 (M3R) have been detected in serum from 9 to
      100 % of patients with SS in addition to anti-SS-A and anti-SS-B antibodies.
      These observations suggest the possibility that anti-M3R antibodies could serve
      as a new diagnostic test in patients with SS. Some anti-M3R antibodies are
      directly responsible for salivary underproduction in patients with SS. Thus,
      strategies designed to eliminate such pathogenic antibodies could help cure SS
      sufferers. In this review, we summarize the current state of knowledge of anti
      M3R autoantibodies in patients with SS and the correlation between B cell
      epitopes and the function of anti-M3R antibodies. 

PMID- 23135884
TI  - Multilineage co-culture of adipose-derived stem cells for tissue engineering.
AB  - Stem cell interactions through paracrine cell signalling can regulate a range of
      cell responses, including metabolic activity, proliferation and differentiation.
      Moving towards the development of optimized tissue-engineering strategies with
      adipose-derived stem cells (ASCs), the focus of this study was on developing
      indirect co-culture models to study the effects of mature adipocytes,
      chondrocytes and osteoblasts on bovine ASC multilineage differentiation. For each
      lineage, ASC differentiation was characterized by histology, gene expression and
      protein expression, in the absence of key inductive differentiation factors for
      the ASCs. Co-culture with each of the mature cell populations was shown to
      successfully induce or enhance lineage-specific differentiation of the ASCs. In
      general, a more homogeneous but lower-level differentiation response was observed
      in co-culture as compared to stimulating the bovine ASCs with inductive
      differentiation media. To explore the role of the Wnt canonical and non-canonical
      signalling pathways within the model systems, the effects of the Wnt inhibitors
      WIF-1 and DKK-1 on multilineage differentiation in co-culture were assessed. The
      data indicated that Wnt signalling may play a role in mediating ASC
      differentiation in co-culture with the mature cell populations.

PMID- 23135885
TI  - Structures and processes for priority-setting by health-care funders: a national
      survey of primary care trusts in England.
AB  - Although explicit priority-setting is advocated in the health services literature
      and supported by the policies of many governments, relatively little is known
      about the extent and ways in which this is carried out at local decision-making
      levels. Our objective was to undertake a survey of local resource allocaters in
      the English National Health Services in order to map and explore current priority
      setting activity. A national survey was sent to Directors of Commissioning in
      English Primary Care Trusts (PCTs). The survey was designed to provide a picture
      of the types of priority-setting activities and techniques that are in place and
      offer some assessment of their perceived effectiveness. There is variation in the
      scale, aims and methods of priority-setting functions across PCTs. A perceived
      strength of priority-setting processes is in relation to the use of particular
      tools and/or development of formal processes that are felt to increase
      transparency. Perceived weaknesses tended to lie in the inability to sufficiently
      engage with a range of stakeholders. Although a number of formal priority-setting
      processes have been developed, there are a series of remaining challenges such as
      ensuring priority-setting goes beyond the margins and is embedded in budget
      management, and the development of disinvestment as well as investment
      strategies. Furthermore, if we are genuinely interested in a more explicit
      approach to priority-setting, then fostering a more inclusive and transparent
      process will be required.

PMID- 23135886
TI  - Evidence-based facilities design in health care: a study of aged care facilities
      in Australia.
AB  - Many facilities for people with dementia have been built with little translation
      of the substantial body of evidence available to inform design. Knowledge
      translation has been described as a four-stage process: awareness, agreement,
      adoption and adherence. This paper identifies where knowledge translation fails
      in the design of aged care facilities for people with dementia. Ten aged care
      facilities were audited using the Environmental Audit Tool. Senior managers and
      architects involved in the facility design were then interviewed to ascertain
      their knowledge of evidence-based principles of dementia design, their agreement
      with the principles and the nature of the obstacles they had encountered in their
      implementation. All architects claimed at least partial awareness of the design
      principles. Five facility managers claimed full awareness. Those facilities
      designed with the input of managers who were fully aware of the principles were
      of significantly higher design quality. There was little agreement on the
      significance of other obstacles. Once aged care providers are aware of the
      principles, they appear to find ways to implement them. If the next generation of
      residential aged care facilities is to be suitable for people with dementia, the
      facility managers must be made aware of the available design principles,
      architects encouraged to be more active in sharing their knowledge and ways found
      to improve the exchange of knowledge between the parties.

PMID- 23135887
TI  - Perspectives on the enablers of e-heath adoption: an international interview
      study of leading practitioners.
AB  - Studies examining the application of information technology to the delivery of
      health-care services often highlight the anticipated benefits. In consequence,
      the benefits of health-care information technology adoption, often referred to as
      'e-health', are widely reported yet there is limited empirical evidence as to how
      such benefits can be realized. Design and implementation guidelines have been
      considered from a socio-technical perspective and there is support for the
      successful application of these principles. There are also some global surveys on
      the topic, but these often report only statistical data and lack richness of
      content. This study draws on existing literature to examine whether the
      principles of health-care information technology adoption are currently applied
      in practice. The paper presents a timely international analysis of the drivers,
      critical enablers and successful deployment strategies for e-health from the
      perspective of leading practitioners. The study considers the adoption of e
      health in 15 countries. A qualitative research design was used and semistructured
      interviews were conducted with 38 thought leaders with expertise in health-care
      information systems and technology. The study presents a comparative analysis of
      the lessons learned from implementing, integrating and embedding e-health in
      practice, and presents a four-phase approach from the perspective of
      practitioners for the accelerated deployment of e-health systems: (i) develop a
      strategic approach, (ii) engage the workforce, (iii) capitalize on information
      technology and (iv) partner with the patient/citizen.

PMID- 23135888
TI  - Comparing the validity of different measures of illness severity: a hospital
      level analysis for acute myocardial infarction.
AB  - The aim of the study is to assess the validity of three measures of illness
      severity (prior year's hospital expenditures, Charlson and Elixhauser indices),
      by analysing the effect of introducing report cards on hospitals treating
      patients with acute myocardial infarction (AMI). Medicare claims data were
      obtained for 1992-1997 for AMI patients aged 65+. We used differences-in
      differences regression analysis to assess the impact of report cards introduced
      in New Jersey and Pennsylvania on the illness severity of AMI patients with and
      without coronary artery bypass graft (CABG) surgery (relative to states without
      report cards). The analysis was conducted at the hospital level. For validation
      we used raw mortality and re-admission trends for AMI patients. While prior
      hospital expenditures suggest a considerable change in the illness severity of
      AMI patients in Pennsylvania relative to other states, raw mortality and re
      admission trends in Pennsylvania are relatively consistent with the trend in the
      rest of the USA. In line with raw mortality and re-admission data, the Charlson
      and Elixhauser indices do not imply a considerable change in the severity of AMI
      patients in Pennsylvania. For CABG patients, illness severity - as measured by
      all three severity measurement methods - decreased after introduction of report
      cards, particularly in Pennsylvania. In conclusion, for AMI patients the Charlson
      and Elixhauser indices are a more valid measure of illness severity than prior
      year's hospital expenditures. After report cards were introduced, healthier AMI
      patients were more likely to receive CABG surgery, while sicker patients were
      avoided.

PMID- 23135889
TI  - The contribution of clinical leadership to service redesign: a naturalistic
      inquiry.
AB  - Numerous policy papers and academic contributions across a range of countries
      emphasize the importance of clinical leadership in health services. This is seen
      as especially vital at a time of simultaneous resource constraints and rising
      demand. Most of the literature in this topic area concerns itself with conceptual
      clarification of types of leadership and with delineation of requisite
      competences. But other work on leadership has emphasized the importance of
      attending to practice in concrete situations in order to identify the dynamics at
      play and the nature of the challenges. The purpose of this article is to
      contribute to this latter task by drawing upon a set of data which reveals
      crucial aspects of the problems facing potential clinical leaders of service
      redesign. This paper reports on the nature and extent of the challenges as
      identified by clinicians of different types as well as managers and
      commissioners.

PMID- 23135890
TI  - Briefing on current and future developments in European Union policy and practice
      in healthcare.

PMID- 23135891
TI  - Carotid intima-media thickness as a biomarker of subclinical atherosclerosis.
AB  - Intima-media thickness of the carotid artery (CIMT) and its increase is
      associated with several cardiovascular risk factors and manifest cardiovascular
      diseases. CIMT is suggested to be an important biomarker of subclinical
      atherosclerosis. CIMT is measured in B-mode ultrasound images of the carotid tree
      as a typical double line of the arterial wall. CIMT is best visible in the
      measurement segment of the distal common carotid artery with lowest measurement
      variability. The measurement is most reliable over a one centimeter-segment with
      automatic or semi-automatic reading methods, which minimises reading errors.
      Further structured training of sonographer and reader is important for valid and
      reproducible results. CIMT is an accepted predictor for future cardiovascular
      events independent of age, gender and cardiovascular risk factors. Measurement
      seems to be best applicable in patients with intermediate risk in order to
      readjust cardiovascular risk. Plaques in the carotid tree and thickening of the
      CIMT are different atherosclerotic processes. From childhood to early adulthood
      CIMT is the only atherosclerotic marker of the carotid tree; plaques occur later
      in life. Both parameters contribute independently to risk assessment for future
      cardio-vascular events. Aims of this review are to outline measurement
      procedures, reproducibility, prognostic value and ability to discriminate healthy
      subject and patients with manifest disease in a practical and scientifically
      contemporary manner.

PMID- 23135892
TI  - Protein-size molecularly imprinted polymer nanogels as synthetic antibodies, by
      localized polymerization with multi-initiators.
AB  - A new approach is proposed for the synthesis of molecularly imprinted polymers
      (MIPs) (synthetic antibodies) as soluble nanogels with sizes close to the size of
      real antibodies. To imprint a molecular memory in particles consisting of only a
      few polymer chains, an initiator carrying multiple iniferter moieties is used.
      This allows for the simultaneous initiation of several polymer chains, and yields
      molecularly imprinted nanogels (17 nm, molecular weight (MW) = 97 kDa) with good
      affinity and selectivity for the target.

PMID- 23135893
TI  - Microstructure and biocompatibility of composite biomaterials fabricated from
      titanium and tricalcium phosphate by spark plasma sintering.
AB  - Important issues in developing hydroxyapatite (HAp)- and titanium (Ti)-based
      composite biomaterials for orthopedic or dental devices include the dissociation
      of HAp during fabrication and its influences in the microstructure and
      biocompatibility of the final composite. During the densification by sintering of
      HAp/Ti composites, Ti reacts with -OH freed from HAp to form TiO2 thus
      dissociated HAp into Ca3(PO4)2, CaO, CaTiO3, TiP, and so forth. To inhibit this
      reaction, composites were fabricated with Ti and 30, 50, and 70 vol % beta
      tricalcium phosphate (beta-TCP) instead of HAp by spark plasma sintering at 1200
      degrees C. It has been observed that after sintering at 1200 degrees C, Ti also
      reacted with TCP, but unlike HAp/Ti composites, the final TCP/Ti composites
      contained significant amounts of unreacted TCP and Ti phases. The initial 70 vol
      % TCP/Ti composite showed compressive strength of 388.5 MPa, Young's modulus of
      3.23 GPa, and Vickers hardness of 361.9 HV after sintering. The in vitro
      cytotoxicity and proliferation of osteoblast cells on the composites surfaces
      showed that the addition of a higher amount of TCP with Ti was beneficial by
      increasing cell viability, cell-composite attachment and proliferation.
      Osteopontin and collagen type II protein expression from osteoblasts cultured
      onto the 70% TCP-Ti composite was also higher than other composites and pure Ti.
      In vivo study verified that within 3 months of implantation in an animal body,
      70% TCP-Ti had an excellent bone-implant interface compared with a pure Ti metal
      implant.

PMID- 23135894
TI  - Behavioral disturbances differentiate frontotemporal lobar degeneration subtypes
      and Alzheimer's disease: evidence from the Frontal Behavioral Inventory.
AB  - BACKGROUND: Behavioral assessment is useful for the diagnosis of frontotemporal
      lobar degeneration (FTLD). We explored the ability of the Frontal Behavioral
      Inventory (FBI) to discriminate between patients with distinct subtypes of FTLD
      and patients with Alzheimer's disease (AD), as well as the influence of
      demographic variables on FBI scores. METHODS: The FBI was administered to the
      caregivers of 87 patients diagnosed with FTLD [64 behavioral variant FTLD, 19
      aphasic variant FTLD (primary progressive aphasia), and 4 motor/extrapyramidal
      variant (corticobasal syndrome)] and 30 patients with AD. Patients with AD were
      older than patients with FTLD. The two groups did not differ with respect to
      duration of illness, level of education, or sex ratio. RESULTS: Age significantly
      predicted disinhibited positive behaviors, such as perseverations and
      irritability, whereas education did not contribute to FBI ratings. Classification
      accuracy for the discrimination of AD and mixed FTLD groups was 81%. Moreover,
      88.3% and 83.7% accuracy was achieved for the discrimination of AD and behavioral
      variant FTLD, and AD and primary progressive aphasia groups, respectively. The
      Total Negative subscale of the FBI, which summarizes the presence of deficit
      (negative) behaviors, was the best discriminator. A cut-off score of 17 provided
      83% sensitivity and 98% specificity in distinguishing between FTLD and AD
      patients. CONCLUSIONS: The FBI is a sensitive and specific tool for the
      differential diagnosis of FTLD from AD. The optimal cut-off point for the
      detection of FTLD patients was lower than that initially proposed.

PMID- 23135895
TI  - Long term survival after trimodal therapy in malignant pleural mesothelioma.
AB  - PRINCIPLES: Trimodal therapy results in long term survival in a small fraction of
      patients with malignant pleural mesothelioma, particularly in patients having
      epithelial histology, R0-resection and no nodal involvement. This study analyses
      the outcome after trimodal therapy including extrapleural pneumonectomy. METHODS:
      From 2000 to 2005 41 patients with histologically verified malignant pleural
      mesothelioma were included. Diagnosis and nodal status were confirmed by surgery.
      21 patients (51%) underwent trimodal therapy with 655 days (63-2,567 days) of
      median follow-up. Postoperative complications, mortality, long term survival and
      recurrence rates were analysed retrospectively. RESULTS: Neoadjuvant chemotherapy
      consisted of a combination of platinum based agents (n = 19) with gemcitabine (n
      = 15) or pemetrexed (n = 4). Extrapleural pneumonectomy was the standard
      procedure for surgery. 13 patients (62%) had postoperative complications. 16
      patients (76%) received postoperative adjuvant radiotherapy. There was a 30-day
      mortality of 4.8% in the trimodal group. Survival rates in the trimodal group
      were 71% after one, 28% after two and 10% after five years. There were no
      significant differences regarding age, tumour stage, cell type or lymph node
      involvement. Tumour recurrence occurred after one and two years in 44% and in 83%
      respectively. CONCLUSIONS: The majority of patients considered for surgical
      resection of malignant pleural mesothelioma have regionally advanced disease. In
      those receiving trimodal therapy long term survival is achieved only in a
      minority of patients. In view of  the time consuming and intensive treatment it
      should be offered only in carefully selected patients as new surgical approaches
      such as pleurectomy/decortication have shown high efficacy rates regarding
      patients' survival.

PMID- 23135896
TI  - Quantum soldering of individual quantum dots.
AB  - Making contact to a quantum dot: Single quantum-dot electronic circuits are
      fabricated by wiring atomically precise metal chalcogenide clusters with
      conjugated molecular connectors. These wired clusters can couple electronically
      to nanoscale electrodes and be tuned to control the charge-transfer
      characteristics (see picture).

PMID- 23135897
TI  - Antihyperlipidemic effect of methanolic extract from Opuntia joconostle seeds in
      mice fed a hypercholesterolemic diet.
AB  - The purpose of this study was to evaluate the hypolipidemic effect of a
      methanolic extract from Opuntia joconostle seeds fed to mice in a
      hypercholesterolemic diet. Acute toxicity of the methanolic extract was
      investigated by an established method. Phenolic composition and antioxidant
      activity were determined by high-performance liquid chromatography and DPPH,
      respectively. The total phenolic content of Opuntia joconostle seeds was 47.85 +/
      1.29 mg gallic acid equivalents/g dry weight. The main phenolic compounds were
      identified as quercetin, rutin, and cafeic acid. Percent inhibition of DPPH+ was
      49.76 +/- 0.49 %. The oral LD50 for the methanolic extract from the Opuntia
      joconostle seeds was >5,000 mg/kg BW. Mice fed a hypercholesterolemic diet for
      six days exhibited significantly (P <= 0.001) higher plasma lipid levels than
      mice fed a normal diet. Remarkably, supplementation with methanolic extract from
      Opuntia joconostle at doses of 1, 2, and 5 g/kg body weight significantly (P <=
      0.001) prevented the increase in total cholesterol, low-density lipoprotein
      cholesterol, triglycerides level, and atherogenic index. Similar concentrations
      of the HDL cholesterol were observed in both treated and control groups. A
      significant dose-dependent reduction in lipid levels was noted for treated groups
      compared to the hypercholesterolemic group. We attribute this result to the
      seeds' phenolic composition. This methanolic extract has potential to be included
      in short-term hypercholesterolemia treatment regimens as it exhibits
      hypolipidemic activity with no apparent toxic manifestations.

PMID- 23135898
TI  - Plant extracts of winter savory, purple coneflower, buckwheat and black elder
      activate PPAR-gamma in COS-1 cells but do not lower blood glucose in Db/db mice
      in vivo.
AB  - The aim of this study was to investigate possible blood glucose-lowering effects
      of plant extracts in vivo for which prior to this a peroxisome proliferator
      activated receptor-gamma activity in vitro was observed. The ability of extracts
      of winter savory, purple coneflower, buckwheat and black elder to dose
      dependently activate peroxisome proliferator-activated receptor-gamma was
      determined in a reporter gene assay in COS-1 cells. For evaluation of glucose
      lowering effects in vivo, db/db mice were fed a diet containing either
      rosiglitazone (0.02 g/kg diet, positive control) or one of the plant extracts
      (0.1 and 1 g/kg diet) for four weeks. Apart from glucose, insulin,
      triacylglycerols, non-esterified fatty acids, cholesterol and adiponectin were
      determined in plasma. All plant extracts showed a dose-dependent peroxisome
      proliferator-activated receptor-gamma-activating effect in vitro. In db/db mice
      none of the plant extracts exerted glucose-lowering effects at the used dosages
      compared to rosiglitazone. Non-esterified fatty acids, triacylglycerols,
      cholesterol, insulin and adiponectin in plasma were not altered by the plant
      extracts as well. Although dose-dependent peroxisome proliferator-activated
      receptor-gamma activity could be shown in COS-1 cells, the experiments in db/db
      mice lacked to confirm any anti-diabetic effect of the plant extracts in vivo and
      emphasizes the importance of verifying cell culture data using an appropriate in
      vivo model.

PMID- 23135899
TI  - Receptor-dependent regulation of dendrite formation of noradrenaline and dopamine
      in non-GABAergic cerebral cortical neurons.
AB  - The present study characterized the receptor-dependent regulation of dendrite
      formation of noradrenaline (NA) and dopamine (DA) in cultured neurons obtained
      from embryonic day 16 rat cerebral cortex. Morphological diversity of cortical
      dendrites was analyzed on various features: dendrite initiation, dendrite
      outgrowth, and dendrite branching. Using a combination of immunocytochemical
      markers of dendrites and GABAergic neurons, we focused on the dendrite morphology
      of non-GABAergic neurons. Our results showed that (1) NA inhibited the dendrite
      branching, (2) beta adrenergic receptor (beta-AR) agonist inhibited the dendrite
      initiation, while promoted the dendrite outgrowth, (3) beta1-AR and beta2-AR were
      present in all the cultured neurons, and both agonists inhibited the dendrite
      initiation, while only beta1-AR agonist induced the dendrite branching; (4) DA
      inhibited the dendrite outgrowth, (5) D1 receptor agonist inhibited the dendrite
      initiation, while promoted the dendrite branching. In conclusion, this study
      compared the effects of NA, DA and their receptors and showed that NA and DA
      regulate different features on the dendrite formation of non-GABAergic cortical
      neurons, depending on the receptors.

PMID- 23135900
TI  - Multiplex PCR to detect four different tomato-infecting pathogens.
AB  - This work was aimed to develop a multiplex PCR assay to detect infectious agents
      such as Clavibacter michiganensis subsp. michiganensis, Fusarium sp, Leveillula
      taurica, and begomoviruses in tomato (Solanum lycopersicum) plants. Specific
      primer sets of each pathogen were designed based on intergenic ribosomal RNA
      sequences for the first three, whereas for begomoviruses, primers were designed
      based on conserved regions. The design also considered that the length (200-800
      bp) of the PCR products was resolvable by electrophoresis; thus 296, 380, 457,
      and 731 bp fragments for Clavibacter, Fusarium, Leveillula, and begomoviruses,
      respectively, were considered. PCR conditions were optimized to amplify all the
      products in a single tube from genomic DNA and circumvent PCR inhibitors from
      infected plants. Finally, when the multiplex PCR assay was tested with tomato
      plants infected with any of the four pathogens, specific PCR products confirmed
      the presence of the pathogens. Optimized PCR multiplex allowed for the accurate
      and simultaneous detection of Clavibacter, Fusarium, Leveillula, and
      begomoviruses in infected plants or seeds from tomato.

PMID- 23135901
TI  - Evaluation of Lactobacillus strains for selected probiotic properties.
AB  - Eleven strains of Lactobacillus collected in the Culture Collection of Dairy
      Microorganisms (CCDM) were evaluated for selected probiotic properties such as
      survival in gastrointestinal fluids, antimicrobial activity, and competition with
      non-toxigenic Escherichia coli O157:H7 for adhesion on Caco-2 cells. The viable
      count of lactobacilli was reduced during 3-h incubation in gastric fluid followed
      by 3-h incubation in intestinal fluid. All strains showed antimicrobial activity
      and the three most effective strains inhibited the growth of at least 16
      indicator strains. Antimicrobial metabolites of seven strains active against
      Lactobacillus and Clostridium indicator strains were found to be sensitive to
      proteinase K and trypsin, which indicates their proteinaceous nature. The degree
      of competitive inhibition of non-toxigenic E. coli O157:H7 adhesion on the
      surface of Caco-2 cells was strain-dependent. A significant decrease (P < 0.05)
      in the number of non-toxigenic E. coli O157:H7 adhering to Caco-2 cells was
      observed with all lactobacilli. Three strains were selected for additional
      studies of antimicrobial activity, i.e., Lactobacillus gasseri CCDM 215,
      Lactobacillus acidophilus CCDM 149, and Lactobacillus helveticus CCDM 82.

PMID- 23135902
TI  - Diagnostic errors and flaws in clinical reasoning: mechanisms and prevention in
      practice.
AB  - Diagnostic errors account for more than 8% of adverse events in medicine and up
      to 30% of malpractice claims. Mechanisms of errors may be related to the working
      environment but cognitive issues are involved in about 75% of the cases, either
      alone or in association with system failures. The majority of cognitive errors
      are not related to knowledge deficiency but to flaws in data collection, data
      integration, and data verification that may lead to premature diagnostic closure.
      This paper reviews some aspects of the literature on cognitive psychology that
      help us to understand reasoning processes and knowledge organisation and
      summarises biases related to clinical reasoning. It reviews the strategies
      described to prevent cognitive diagnostic errors. Many approaches propose
      awareness and reflective practice during daily activities, but the improvement of
      the quality of training at the pre-graduate, postgraduate and continuous levels,
      by using evidence-based education, should also be considered. Several conditions
      must be fulfilled to increase the understanding, the prevention, and the
      correction of diagnostic errors related to clinical reasoning: physicians must be
      willing to understand their own reasoning and decision processes; training
      efforts should be provided during the whole continuum of a clinician's career;
      and the involvement of medical schools, teaching hospitals, and medical societies
      in medical education research should be increased to improve evidence about error
      prevention.

PMID- 23135903
TI  - Chirality of anisotropic metal nanowires with a distinct multihelix.
AB  - Two-dimensional (2D) anisotropic silver nanowire (AgNW) arrays, fabricated inside
      chiral mesoporous silica (CMS), exhibited strong and tunable plasmon circular
      dichroism (CD) signals in the visible and near-IR regions due to collective
      dipole coupling between the anisotropic AgNWs. The multihelix with a helical
      channel orientation and helical arrays of opposite handedness in CMS played a
      predominant effects on the transversal and longitudinal chirality of the AgNWs,
      respectively.This behavior differs from both isotropic-nanoparticle and single
      helix-induced CD responses. This system will provide new insight into the optical
      activity of metal inorganic nanoparticles capped with chiral organic molecules
      and assembled in chiral environments.

PMID- 23135904
TI  - Growth and osteogenic differentiation of alveolar human bone marrow-derived
      mesenchymal stem cells on chitosan/hydroxyapatite composite fabric.
AB  - Scaffolds can be used for tissue engineering because they can serve as templates
      for cell adhesion and proliferation for tissue repair. In this study,
      chitosan/hydroxyapatite (CS/HAp) composites were prepared by coprecipitation
      synthesis. Then, CS and CS/HAp fabrics were prepared by wet spinning. CS fibers
      with a diameter of 15 +/- 1.3 MUm and CS/HAp fibers with a diameter of 22 +/- 1.2
      MUm were successfully produced; incorporation of HAp into the CS/HAp fibers was
      confirmed by X-ray diffraction analysis. Biological in vitro evaluations showed
      that human mesenchymal stem cells (hMSCs) cultured on CS/HAp fabric showed
      increased proliferation compared to those cultured on pure CS fabric, which was
      observed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      assay, DNA content assay, and [(3) H] thymidine incorporation assay. Neither the
      CS nor CS/HAp scaffold exhibited any cytotoxicity to hMSCs, as shown by viability
      staining and cytotoxicity fluorescence image assays. After 10 days of culturing,
      the attachment of cells onto the scaffold was observed by scanning electron
      microscopy. Furthermore, under osteogenic differentiation conditions, alkaline
      phosphatase (ALP) activity and calcium accumulation was higher in cells cultured
      on the CS/HAp scaffold than in cells cultured on the CS scaffold. The mRNA
      expression of osteoblast markers, including ALP, osteocalcin, Co1Ia1, and runt
      related transcription factor 2, was higher in cells cultured on CS/HAp than in
      cells cultured on the CS fabric. The results of this study indicate that the
      CS/HAp composite fabric may serve as a good scaffold for bone tissue engineering
      applications.

PMID- 23135905
TI  - Electric field-induced dipole switching at the donor/acceptor interface in
      organic solar cells.
AB  - Order of dipole moment layers at donor and acceptor interfaces in bilayer organic
      solar cells is manipulated reversibly by applying bias voltages. The energy level
      shifts at the interfaces induce reversible changes in the open circuit voltage
      and the diode properties. This finding could lead to a better understanding of
      the structure-property relationship at the materials interfaces in organic
      optoelectronic devices.

PMID- 23135906
TI  - Temporal lobe volume abnormalities precede the prodrome: a study of children
      presenting antecedents of schizophrenia.
AB  - Distributed abnormalities of gray matter (GM) and white matter (WM) volume
      characterize individuals experiencing their first episode of schizophrenia.
      Regions of abnormality are present already, albeit less extensively, during the
      prodromal phase of illness. This study aimed to determine whether putatively at
      risk children, aged 9-12 years, who present multiple antecedents of schizophrenia
      (ASz), display GM and WM volume abnormalities relative to typically developing
      (TD) children presenting no antecedents. Structural magnetic resonance images
      were acquired for 20 ASz children and 20 TD children matched on age, sex, and IQ.
      Whole-brain differences in GM and WM volume were determined using voxel-based
      morphometry. Relative to the TD group, ASz children showed significantly
      decreased GM volume in the right middle temporal gyrus (MTG) and increased GM
      volume in the left superior-middle temporal gyri (P < 0.05, cluster correction).
      WM volume was significantly increased in ASz children relative to TD children in
      a cluster encompassing the left inferior parietal lobe, occipital lobe, and
      superior temporal gyrus. Post-hoc analyses indicated that these abnormalities
      were not limited to ASz children who self-reported auditory hallucinations on
      questionnaire. Our findings suggest that children aged 9-12 years who present
      multiple ASz are characterized by abnormalities of GM and WM volume in the
      temporal lobes, comprising a subset of the regions affected in first-episode
      schizophrenia and in the prodromal phase of illness. These preliminary findings
      indicate that structural brain abnormalities associated with schizophrenia may be
      detected in putatively at-risk, preprodromal children. Prospective studies
      following the brain development of at-risk children are needed. 

PMID- 23135907
TI  - Glutathione-deficient mice have increased sensitivity to transplacental
      benzo[a]pyrene-induced premature ovarian failure and ovarian tumorigenesis.
AB  - Polycyclic aromatic hydrocarbons (PAH) such as benzo[a]pyrene (BaP) are
      ubiquitous environmental pollutants found in tobacco smoke, air pollution, and
      grilled foods. Prenatal exposure to BaP causes premature reproductive senescence
      in mice, and other PAHs are transplacental ovarian carcinogens. Glutathione (GSH)
      is critical for detoxification of the reactive metabolites of PAHs. Therefore, we
      hypothesized that mice that are genetically deficient in GSH synthesis, due to
      deletion of the modifier subunit of glutamate cysteine ligase (Gclm), the rate
      limiting enzyme in GSH synthesis, have increased destruction of oogonia,
      premature ovarian failure, and ovarian tumorigenesis after transplacental BaP
      exposure compared with Gclm(+/+) females. Gclm(+/-) female and male mice were
      mated, and dams were treated with 0, 2, or 10 mg/kg/d BaP in sesame oil by gavage
      from gestational days 7 to 16. Compared with oil-treated F1 females of the same
      genotype, Gclm(-/-) prenatally BaP-treated females had significantly greater
      decrements in offspring production than Gclm(+/+) BaP-treated females. Similarly,
      we observed significant BaP dose * Gclm genotype interactions on ovarian follicle
      counts and ovarian tumor multiplicity at 7.5 months of age, with Gclm(-/-)
      females having greater decrements in follicle numbers and more ovarian tumors in
      response to prenatal BaP exposure than Gclm(+/+) females. The ovarian tumors were
      positive for the epithelial marker cytokeratin. Our results show that prenatal
      exposure of females to BaP causes premature ovarian failure and ovarian
      tumorigenesis and that embryonic GSH deficiency due to deletion of Gclm increases
      sensitivity to these transplacental ovarian effects of BaP.

PMID- 23135908
TI  - Cisplatin selects for multidrug-resistant CD133+ cells in lung adenocarcinoma by
      activating Notch signaling.
AB  - Platinum-based chemotherapy is the first-line treatment for non-small cell lung
      cancer, but recurrence occurs in most patients. Recent evidence suggests that
      CD133(+) cells are the cause of drug resistance and tumor recurrence. However,
      the correlation between chemotherapy and regulation of CD133(+) cells has not
      been investigated methodically. In this study, we revealed that CD133(+) lung
      cancer cells labeled by a human CD133 promoter-driven GFP reporter exhibited drug
      resistance and stem cell characteristics. Treatment of H460 and H661 cell lines
      with low-dose cisplatin (IC(20)) was sufficient to enrich CD133(+) cells, to
      induce DNA damage responses, and to upregulate ABCG2 and ABCB1 expression, which
      therefore increased the cross-resistance to doxorubicin and paclitaxel. This
      cisplatin-induced enrichment of CD133(+) cells was mediated through Notch
      signaling as judged by increased levels of cleaved Notch1 (NICD1). Pretreatment
      with the gamma-secretase inhibitor, N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S
      phenylglycine t-butyl ester (DAPT), or Notch1 short hairpin RNAs (shRNA)
      remarkably reduced the cisplatin-induced enrichment of CD133(+) cells and
      increased the sensitivity to doxorubicin and paclitaxel. Ectopic expression of
      NICD1 reversed the action of DAPT on drug sensitivity. Immunohistochemistry
      showed that CD133(+) cells were significantly increased in the relapsed tumors in
      three of six patients with lung cancer who have received cisplatin treatment. A
      similar effect was observed in animal experiments as cisplatin treatment
      increased Notch1 cleavage and the ratio of CD133(+) cells in engrafted tumors.
      Intratumoral injection of DAPT with cisplatin treatment significantly reduced
      CD133(+) cell number. Together, our results showed that cisplatin induces the
      enrichment of CD133(+) cells, leading to multidrug resistance by the activation
      of Notch signaling.

PMID- 23135909
TI  - Genomic profiling of isolated circulating tumor cells from metastatic breast
      cancer patients.
AB  - Molecular characterization of circulating tumor cells (CTC) from blood is
      technically challenging because cells are rare and difficult to isolate. We
      developed a novel approach to isolate CTCs from blood via immunomagnetic
      enrichment followed by fluorescence-activated cell sorting (IE-FACS). Isolated
      CTCs were subjected to genome-wide copy number analysis via array comparative
      genomic hybridization (aCGH). In clinical studies, CTCs were isolated from 181
      patients with metastatic breast cancer, 102 of which were successfully profiled,
      including matched archival primary tumor from five patients. CTCs revealed a wide
      range of copy number alterations including those previously reported in breast
      cancer. Comparison with two published aCGH datasets of primary breast tumors
      revealed similar frequencies of recurrent genomic copy number aberrations. In
      addition, serial testing of CTCs confirmed reproducibility and indicated genomic
      change over time. Comparison of CTCs with matched archival primary tumors
      confirmed shared lineage as well as some divergence. We showed that it is
      feasible to isolate CTCs away from hematopoietic cells with high purity through
      IE-FACS and profile them via aCGH analysis. Our approach may be used to explore
      genomic events involved in cancer progression and to monitor therapeutic efficacy
      of targeted therapies in clinical trials in a relatively noninvasive manner.

PMID- 23135910
TI  - Overexpression of the mitochondrial folate and glycine-serine pathway: a new
      determinant of methotrexate selectivity in tumors.
AB  - Previous studies have documented the roles of transport via the reduced folate
      carrier, retention via polyglutamylation, and increased levels of the target
      enzyme, dihydrofolate reductase in sensitivity to methotrexate. Recent studies
      have shown that the mitochondrial enzymes in the cellular metabolism of serine,
      folate, and glycine are overexpressed in a subset of human cancers and that their
      expression is required for tumor maintenance. In this Perspective article, we
      propose that the expression of mitochondrial enzymes in the metabolism of serine
      and glycine, in addition to those involved in folate metabolism, are determinants
      of the response to methotrexate. Furthermore, we show that myc activation in
      tumors is associated with upregulation of these enzymes. We propose that patients
      whose tumors show this phenotype will be sensitive to folate antagonists
      targeting thymidylate or purine biosynthesis.

PMID- 23135911
TI  - S100A9 is a novel ligand of EMMPRIN that promotes melanoma metastasis.
AB  - The calcium-binding proteins S100A8 and S100A9 can dimerize to form calprotectin,
      the release of which during tissue damage has been implicated in inflammation and
      metastasis. However, receptor(s) mediating the physiologic and pathophysiologic
      effects of this damage-associated "danger signal" are uncertain. In this study,
      searching for candidate calprotectin receptors by affinity isolation-mass
      spectrometry, we identified the cell surface glycoprotein EMMPRIN/BASIGIN
      (CD147/BSG). EMMPRIN specifically bound to S100A9 but not S100A8. Induction of
      cytokines and matrix metalloproteases (MMP) by S100A9 was markedly downregulated
      in melanoma cells by attenuation of EMMPRIN. We found that EMMPRIN signaling used
      the TNF receptor-associated factor TRAF2 distinct from the known S100-binding
      signaling pathway mediated by RAGE (AGER). S100A9 strongly promoted migration
      when EMMPRIN was highly expressed, independent of RAGE, whereas EMMPRIN blockade
      suppressed migration by S100A9. Immunohistologic analysis of melanomas revealed
      that EMMPRIN was expressed at both the invasive edge of lesions and the adjacent
      epidermis, where S100A9 was also strongly expressed. In epidermal-specific
      transgenic mice, tail vein-injected melanoma accumulated in skin expressing
      S100A9 but not S100A8. Together, our results establish EMMPRIN as a receptor for
      S100A9 and suggest the therapeutic use in targeting S100A9-EMMPRIN interactions.

PMID- 23135912
TI  - An integrated genome-wide approach to discover tumor-specific antigens as
      potential immunologic and clinical targets in cancer.
AB  - Tumor-specific antigens (TSA) are central elements in the immune control of
      cancers. To systematically explore the TSA genome, we developed a computational
      technology called heterogeneous expression profile analysis (HEPA), which can
      identify genes relatively uniquely expressed in cancer cells in contrast to
      normal somatic tissues. Rating human genes by their HEPA score enriched for
      clinically useful TSA genes, nominating candidate targets whose tumor-specific
      expression was verified by reverse transcription PCR (RT-PCR). Coupled with HEPA,
      we designed a novel assay termed protein A/G-based reverse serological evaluation
      (PARSE) for quick detection of serum autoantibodies against an array of putative
      TSA genes. Remarkably, highly tumor-specific autoantibody responses against seven
      candidate targets were detected in 4% to 11% of patients, resulting in
      distinctive autoantibody signatures in lung and stomach cancers. Interrogation of
      a larger cohort of 149 patients and 123 healthy individuals validated the
      predictive value of the autoantibody signature for lung cancer. Together, our
      results establish an integrated technology to uncover a cancer-specific antigen
      genome offering a reservoir of novel immunologic and clinical targets.

PMID- 23135913
TI  - MYC acts via the PTEN tumor suppressor to elicit autoregulation and genome-wide
      gene repression by activation of the Ezh2 methyltransferase.
AB  - The control of normal cell growth is a balance between stimulatory and inhibitory
      signals. MYC is a pleiotropic transcription factor that both activates and
      represses a broad range of target genes and is indispensable for cell growth.
      Whereas much is known about gene activation by MYC, there is no established
      mechanism for the majority of MYC-repressed genes. We report that MYC
      transcriptionally activates the PTEN tumor suppressor in normal cells to
      inactivate the phosphoinositide 3-kinase (PI3K) pathway, thus suppressing AKT
      activation. Suppression of AKT enhances the activity of the EZH2 histone
      methyltransferase, a subunit of the epigenetic repressor Polycomb Repressive
      Complex 2 (PRC2), while simultaneously stabilizing the protein. MYC-mediated
      enhancement in EZH2 protein level and activity results in local and genome-wide
      elevation in the repressive H3K27me3 histone modification, leading to widespread
      gene repression including feedback autoregulation of the MYC gene itself.
      Depletion of either PTEN or EZH2 and inhibition of the PI3K/AKT pathway leads to
      gene derepression. Importantly, expression of a phospho-defective EZH2 mutant is
      sufficient to recapitulate nearly half of all MYC-mediated gene repression. We
      present a novel epigenetic model for MYC-mediated gene repression and propose
      that PTEN and MYC exist in homeostatic balance to control normal growth, which is
      disrupted in cancer cells.

PMID- 23135914
TI  - PD-1-expressing tumor-infiltrating T cells are a favorable prognostic biomarker
      in HPV-associated head and neck cancer.
AB  - Head and neck cancers positive for human papillomavirus (HPV) have a more
      favorable clinical outcome than HPV-negative cancers, but it is unknown why this
      is the case. We hypothesized that prognosis was affected by intrinsic features of
      HPV-infected tumor cells or differences in host immune response. In this study,
      we focused on a comparison of regulatory Foxp3(+) T cells and programmed death-1
      (PD-1)(+) T cells in the microenvironment of tumors that were positive or
      negative for HPV, in two groups that were matched for various clinical and
      biologic parameters. HPV-positive head and neck cancers were more heavily
      infiltrated by regulatory T cells and PD-1(+) T cells and the levels of PD-1(+)
      cells were positively correlated with a favorable clinical outcome. In explaining
      this paradoxical result, we showed that these PD-1(+) T cells expressed
      activation markers and were functional after blockade of the PD-1-PD-L1 axis in
      vitro. Approximately 50% of PD-1(+) tumor-infiltrating T cells lacked Tim-3
      expression and may indeed represent activated T cells. In mice, administration of
      a cancer vaccine increased PD-1 on T cells with concomitant tumor regression. In
      this setting, PD-1 blockade synergized with vaccine in eliciting antitumor
      efficacy. Our findings prompt a need to revisit the significance of PD-1
      infiltrating T cells in cancer, where we suggest that PD-1 detection may reflect
      a previous immune response against tumors that might be reactivated by PD-1/PD-L1
      blockade.

PMID- 23135915
TI  - Epigenetic regulation by Z-DNA silencer function controls cancer-associated ADAM
      12 expression in breast cancer: cross-talk between MeCP2 and NF1 transcription
      factor family.
AB  - A disintegrin and metalloprotease domain-containing protein 12 (ADAM-12) is
      upregulated in many human cancers and promotes cancer metastasis. Increased
      urinary level of ADAM-12 in breast and bladder cancers correlates with disease
      progression. However, the mechanism of its induction in cancer remains less
      understood. Previously, we reported a Z-DNA-forming negative regulatory element
      (NRE) in ADAM-12 that functions as a transcriptional suppressor to maintain a low
      level expression of ADAM-12 in most normal cells. We now report here that
      overexpression of ADAM-12 in triple-negative MDA-MB-231 breast cancer cells and
      breast cancer tumors is likely due to a marked loss of this Z-DNA-mediated
      transcriptional suppression function. We show that Z-DNA suppressor operates by
      interaction with methyl-CpG-binding protein, MeCP2, a prominent epigenetic
      regulator, and two members of the nuclear factor 1 family of transcription
      factors, NF1C and NF1X. While this tripartite interaction is highly prevalent in
      normal breast epithelial cells, both in vitro and in vivo, it is significantly
      lower in breast cancer cells. Western blot analysis has revealed significant
      differences in the levels of these 3 proteins between normal mammary epithelial
      and breast cancer cells. Furthermore, we show, by NRE mutation analysis, that
      interaction of these proteins with the NRE is necessary for effective suppressor
      function. Our findings unveil a new epigenetic regulatory process in which Z
      DNA/MeCP2/NF1 interaction leads to transcriptional suppression, loss of which
      results in ADAM-12 overexpression in breast cancer cells.

PMID- 23135916
TI  - Combination therapy targeting the Chk1 and Wee1 kinases shows therapeutic
      efficacy in neuroblastoma.
AB  - Neuroblastoma is uniquely sensitive to single-agent inhibition of the DNA damage
      checkpoint kinase Chk1, leading us to examine downstream effectors of this
      pathway and identify mitotic regulator Wee1 as an additional therapeutic target
      in this disease. Wee1 was overexpressed in both neuroblastoma cell lines and high
      risk patient tumors. Genetic or pharmacologic abrogation of Wee1 signaling
      results in marked cytotoxicity in 10 of 11 neuroblastoma cell lines with a median
      IC(50) of 300 nmol/L for the Wee1-selective small-molecule inhibitor MK-1775.
      Murine tumor lines derived from mice that were either heterozygous or homozygous
      for MycN were particularly sensitive to single-agent inhibition of Wee1 (IC(50)s
      of 160 and 62 nmol/L, respectively). Simultaneous pharmacologic inhibition of
      Chk1 and Wee1 acted in a synergistic fashion to further impede neuroblastoma cell
      growth in vitro, in a manner greater than the individual inhibitors either alone
      or combined with chemotherapy. Combination Chk1 and Wee1 inhibition also revealed
      in vivo efficacy in neuroblastoma xenografts. Taken together, our results show
      that neuroblastoma cells depend on Wee1 activity for growth and that inhibition
      of this kinase may serve as a therapeutic for patients with neuroblastoma.

PMID- 23135917
TI  - RhoB differentially controls Akt function in tumor cells and stromal endothelial
      cells during breast tumorigenesis.
AB  - Tumors are composed of cancer cells but also a larger number of diverse stromal
      cells in the tumor microenvironment. Stromal cells provide essential supports to
      tumor pathophysiology but the distinct characteristics of their signaling
      networks are not usually considered in developing drugs to target tumors. This
      oversight potentially confounds proof-of-concept studies and increases drug
      development risks. Here, we show in established murine and human models of breast
      cancer how differential regulation of Akt by the small GTPase RhoB in cancer
      cells or stromal endothelial cells determines their dormancy versus outgrowth
      when angiogenesis becomes critical. In cancer cells in vitro or in vivo, RhoB
      functions as a tumor suppressor that restricts EGF receptor (EGFR) cell surface
      occupancy as well as Akt signaling. However, after activation of the angiogenic
      switch, RhoB functions as a tumor promoter by sustaining endothelial Akt
      signaling, growth, and survival of stromal endothelial cells that mediate tumor
      neoangiogenesis. Altogether, the positive impact of RhoB on angiogenesis and
      progression supercedes its negative impact in cancer cells themselves. Our
      findings elucidate the dominant positive role of RhoB in cancer. More generally,
      they illustrate how differential gene function effects on signaling pathways in
      the tumor stromal component can complicate the challenge of developing
      therapeutics to target cancer pathophysiology.

PMID- 23135918
TI  - Dendritic luminescent gold(III) complexes for highly efficient solution
      processable organic light-emitting devices.
AB  - Emission control: carbazole-based dendritic alkynylgold(III) complexes have been
      evaluated as phosphorescent emitters in organic light-emitting devices. The
      energy as well as the bathochromic shift of the emissions can be tuned
      effectively through a control of the dendrimer generation. The optimized devices
      show high current and external quantum efficiencies of up to 24.0 cd A(-1) and
      7.8 %, respectively.

PMID- 23135919
TI  - Fungal disease of the nose and sinuses: an updated overview.
AB  - Fungal diseases of the nose and sinuses encompasses a diverse spectrum of
      disease. Clinical manifestations are largely dependent upon the immune status of
      the host, as, given the ubiquitous nature of these organisms, exposure is
      unavoidable. Asymptomatic colonization of the nasal passages by fungi warrants no
      treatment and is common, while allergic fungal rhinosinusitis is challenging and
      often requires a combined approach of surgical intervention, immunotherapy, and
      corticosteroid administration. A diagnosis requires a combination of IgE immune
      reactivity, eosinophilic infiltration, and fungi recovery. Similarly, invasive
      disease may present only after several months of slowly progressive disease, or
      in rapid and fulminant fashion in the appropriate host. A differentiation of
      these overlapping syndromes and the pathophysiologic processes at play, and
      recommended treatment algorithms, are the focus of this review.

PMID- 23135921
TI  - Cranio-maxillofacial injuries in victims of interpersonal violence.
AB  - BACKGROUND: Recent research has indicated an increase in the severity of head
      injuries in Switzerland. The aim of the present study was to describe the
      epidemiological features of cranio-maxillofacial (CMF) injuries due to
      interpersonal violence in patients at the Bern University Hospital Emergency
      Department (ED), based on injury patterns. METHODS: Retrospective analysis was
      performed on data collected during an 11-year period between 1 January 2000 and
      31 December 2010 covering 1,585 patients. A distinction was drawn between
      neurocranial and maxillofacial injuries, and two time periods (2000-2004 and 2005
      2010) were compared. RESULTS: The patients' median age at the time of admission
      was 26 years (range 12-82), and 1,473 of 1,585 patients (92.9%) were males.
      Referrals increased from an annual average of 119.6 in 2000-2004 to 164.5 in 2005
      2010 (p <0.001). Severe neurocranial injuries doubled in number - from an annual
      average of 4.2 in 2000-2004 to 8.5 in 2005-2010 (p = 0.010). Maxillofacial
      injuries seen in the ED increased from an average of 163.6 per year in 2000-2004
      to 247.8 in 2005-2010 (p <0.001), and the number of maxillofacial injuries per
      patient increased from 1.37 to 1.51 (p = 0.015). CONCLUSIONS: Cranio
      maxillofacial (CMF) injuries chiefly affect young people, and thus impose a heavy
      economic burden on society. Synergies are possible between the implementation of
      violence prevention strategies and other prevention objectives in every age group
      and intervention area.

PMID- 23135922
TI  - Brief report: Mechanism of extravasation of infused stem cells.
AB  - In order for bloodborne stem cells to be effective in tissue regeneration, cells
      must cross vessel walls and enter the parenchyma. Although such transmigration
      does occur, the mechanism remains elusive. Leukocytes invade tissue by
      diapedesis; stem cells are commonly assumed to do likewise, but evidence is
      lacking. Cardiac-derived regenerative cells and multicellular cardiospheres
      (CSPs) were infused into the coronary vessels of rat hearts. Serial histology
      revealed a novel mechanism of cell transmigration, "active vascular expulsion,"
      which underlies the extravasation of infused cells and cell aggregates. In this
      mechanism, the vascular barrier undergoes extensive remodeling, while the cells
      themselves are relatively passive. The mechanism was confirmed in vivo by serial
      intravital microscopy of CSP extravasation in a dorsal skin flap model. Integrins
      and matrix metalloproteinases play critical roles in active vascular expulsion.
      In vitro models revealed that active vascular expulsion is generalizable to other
      stem cell types and to breast cancer cells. Recognition of active vascular
      expulsion as a mechanism for transvascular cell migration opens new opportunities
      to enhance the efficacy of vascularly delivered cell therapy.

PMID- 23135923
TI  - Pitfalls in the interpretation of standardised quality of life instruments for
      individual patients? A qualitative study in colorectal cancer.
AB  - PURPOSE: Despite being readily available and practical to administer,
      standardised instruments are not widely used in clinical practice. Concerns have
      been raised about the validity of applying such data to individuals. The aim of
      this qualitative study was to explore the practical difficulties of interpreting
      standardised HrQoL data for individual patients. METHODS: A purposive sample of
      20 patients with colorectal cancer was chosen from 210 participants in a
      prospective HrQoL study. In an in-depth interview, individual participants were
      asked about their experiences and to review the accuracy of their own HrQoL data,
      collected over preceding months using four different instruments (FACT-C QLQ
      C30/CR38 SF12 and EQ-5D). A framework qualitative analysis was used to develop
      emerging themes. RESULTS: A number of themes emerged from the analysis to explain
      why disparity arose between the patients' experiences and the questionnaire data
      in certain situations. These included weakly worded items that over emphasised
      health problems, incongruous items within scales causing unpredictable scores,
      insufficient levels of response causing insensitivity, and unrecognised reversal
      of item direction causing contradictory scores. Exogenous factors such as mood
      and co-morbidities also influenced HrQoL reporting. CONCLUSIONS: Data from
      standardised instruments can be used to measure the HrQoL of individuals in
      clinical practice, but the instruments used need careful selection and
      interpretation. Appropriate guidance linked to the themes of this study is
      provided.

PMID- 23135924
TI  - Evaluation of item candidates for a diabetic retinopathy quality of life item
      bank.
AB  - PURPOSE: We are developing an item bank assessing the impact of diabetic
      retinopathy (DR) on quality of life (QoL) using a rigorous multi-staged process
      combining qualitative and quantitative methods. We describe here the first two
      qualitative phases: content development and item evaluation. METHODS: After a
      comprehensive literature review, items were generated from four sources: (1) 34
      previously validated patient-reported outcome measures; (2) five published
      qualitative articles; (3) eight focus groups and 18 semi-structured interviews
      with 57 DR patients; and (4) seven semi-structured interviews with diabetes or
      ophthalmic experts. Items were then evaluated during 3 stages, namely binning
      (grouping) and winnowing (reduction) based on key criteria and panel consensus;
      development of item stems and response options; and pre-testing of items via
      cognitive interviews with patients. RESULTS: The content development phase
      yielded 1,165 unique items across 7 QoL domains. After 3 sessions of binning and
      winnowing, items were reduced to a minimally representative set (n = 312) across
      9 domains of QoL: visual symptoms; ocular surface symptoms; activity limitation;
      mobility; emotional; health concerns; social; convenience; and economic. After 8
      cognitive interviews, 42 items were amended resulting in a final set of 314
      items. CONCLUSIONS: We have employed a systematic approach to develop items for a
      DR-specific QoL item bank. The psychometric properties of the nine QoL subscales
      will be assessed using Rasch analysis. The resulting validated item bank will
      allow clinicians and researchers to better understand the QoL impact of DR and DR
      therapies from the patient's perspective.

PMID- 23135925
TI  - Amino-terminated generation 2 poly(amidoamine) dendrimer as a potential broad
      spectrum, nonresistance-inducing antibacterial agent.
AB  - The treatment of septicemia caused by antibiotic-resistant bacteria is a great
      challenge in the clinic. Because traditional antibiotics inevitably induce
      bacterial resistance, which is responsible for many treatment failures, there is
      an urgent need to develop novel antibiotic drugs. Amino-terminated
      Poly(amidoamine) dendrimers (PAMAM-NH(2)) are reported to have antibacterial
      activities. However, previous studies focused on high generations of PAMAM-NH(2),
      which have been found to exhibit high toxicities. The present study aimed to
      clarify whether low generations of PAMAM-NH(2) could be used as novel
      antibacterial agents. We found that generation 2 (G2.0) PAMAM-NH(2) showed
      significant antibacterial effects against antibiotic-sensitive and antibiotic
      resistant strains but exhibited little toxicity to human gastric epithelial cells
      and did not induce antibiotic resistance in bacteria. Scanning and transmission
      electron microscopy analyses suggested that G2.0 PAMAM-NH(2) might inhibit the
      growth of bacteria by destroying their cell membranes. The administration of G2.0
      PAMAM-NH(2) dose-dependently improved the animal survival rate of mice infected
      with extended-spectrum beta lactamase-producing Escherichia coli (ESBL-EC) and of
      animals infected with a combination of ESBL-EC and methicillin-resistant
      Staphylococcus aureus. A treatment regimen of 10 mg/kg of G2.0 PAMAM-NH(2)
      starting 12 h before inoculation followed by 10 mg/kg at 0.5 h after inoculation
      rescued 100% of singly infected mice and 60% of multiply infected mice. The
      protective effects were associated with the reduction of the bacterial titers in
      the blood and with the morphological amelioration of infected tissues. These
      findings demonstrate that the G2.0 PAMAM-NH(2) is a potential broad-spectrum and
      nonresistance-inducing antibiotic agent with relatively low toxicity.

PMID- 23135926
TI  - Target-mediated disposition model describing the dynamics of IL12 and IFNgamma
      after administration of a mifepristone-inducible adenoviral vector for IL-12
      expression in mice.
AB  - Interleukin-12 (IL12) is a cytokine with potential applications in the treatment
      of cancer given the potent immune response that it triggers, in part due to its
      ability to stimulate expression of interferon-gamma (IFNgamma). To avoid the
      toxicity associated with systemic exposure to IL12, a high-capacity adenoviral
      vector carrying a liver-specific, mifepristone-inducible IL12 expression system
      (HC-Ad/RUmIL12) has been developed. However, the maintenance of IL12 expression
      at therapeutic levels is compromised by the inhibitory effect of IFNgamma on
      inducible systems. The aim of this work is to develop a semi-mechanistic model to
      characterize the relationship between IL12 and IFNgamma in wild-type and knock
      out mice for the IFNgamma receptor treated with HC-Ad/RUmIL12 under different
      dosing regimens in order to better understand the key mechanisms controlling the
      system. Rapid binding was considered to account for target-mediated disposition
      exhibited by both cytokines (equilibrium dissociation constant were 18 and 2.28
      pM for IL12 and IFNgamma, respectively). The final model included: (1) IFNgamma
      receptor turnover, (2) irreversible free cytokine elimination from the serum
      compartment, (3) internalization of the IL12 receptor complex, (4) IL12
      expression upregulated by the co-administration of the adenoviral vector and
      mifepristone and downregulated by the IFNgamma receptor, and (5) synthesis of
      IFNgamma controlled by the relative increments in the bound IL12. In conclusion,
      a model simultaneously describing the kinetics of IL12 and IFNgamma in the
      context of gene therapy was developed and validated with additional data. The
      model was applied to design an experimental dosing protocol intended to maintain
      sustained therapeutic IL12 levels.

PMID- 23135927
TI  - Validation of a ligand binding assay using dried blood spot sampling.
AB  - Dried blood spots (DBS) technology has been introduced as a microsampling
      alternative to traditional plasma or serum sampling for pharmacokinetics or
      toxicokinetics evaluation. The application of DBS has been established for many
      small molecule drugs at discovery, nonclinical, and clinical stages. However, the
      application of DBS for large molecule therapeutics development is not yet well
      established. This article describes the method validation of a ligand binding
      assay (LBA) for DBS sampling of a therapeutic monoclonal antibody-AMG 162
      (Denosumab). The original serum LBA was modified for the DBS method. A fit-for
      purpose method validation was performed to evaluate accuracy and precision,
      selectivity, dilutional linearity, and stability. In addition, the parameters
      relevant to DBS, such as spot volume, extraction recovery, whole blood stability,
      and hematocrit effects, were evaluated. The validation results demonstrated assay
      robustness with inter-assay precision of <= 19%, inter-assay accuracy of <= 9%,
      and total error of <= 24%. Selectivity, extraction recovery, dilutional
      linearity, and stability were demonstrated. The validation results revealed some
      limitations of the possible effect of blood hematocrit on therapeutic
      concentration measurements and the caution required using whole blood for
      standards and quality controls preparation. This is the first article to describe
      a thorough method validation of an LBA using DBS for a therapeutic monoclonal
      antibody. The lessons learned can serve as a model process for future method
      validation of other LBAs for large molecule therapeutics or biomarkers using the
      DBS sampling method.

PMID- 23135928
TI  - Spiroketal-based phosphorus ligands for highly regioselective hydroformylation of
      terminal and internal olefins.
AB  - A new class of bidentate phosphoramidite ligands, based on a spiroketal backbone,
      has been developed for the rhodium-catalyzed hydroformylation reactions. A range
      of short- and long-chain olefins, were found amenable to the protocol, affording
      high catalytic activity and excellent regioselectivity for the linear aldehydes.
      Under the optimized reaction conditions, a turnover number (TON) of up to
      2.3*10(4) and linear to branched ratio (l/b) of up to 174.4 were obtained in the
      Rh(I)-catalyzed hydroformylation of terminal olefins. Remarkably, the catalysts
      were also found to be efficient in the isomerization-hydroformylation of some
      internal olefins, to regioselectively afford the linear aldehydes with TON values
      of up to 2.0*10(4) and l/b ratios in the range of 23.4-30.6. X-ray
      crystallographic analysis revealed the cis coordination of the ligand in the
      precatalyst [Rh(3d)(acac)], whereas NMR and IR studies on the catalytically
      active hydride complex [HRh(CO)(2)(3d)] suggested an eq-eq coordination of the
      ligand in the species.

PMID- 23135929
TI  - Pathogenic potential of Bacillus cereus strains as revealed by phenotypic
      analysis.
AB  - The Bacillus cereus pathogenic spectrum ranges from strains used as probiotics to
      human-lethal strains. However, prediction of the pathogenic potential of a strain
      remains difficult. Here, we show that food poisoning and clinical strains can be
      differentiated from harmless strains on the basis of host colonization
      phenotypes.

PMID- 23135930
TI  - Three-way comparison of BBL CHROMagar MRSA II, MRSASelect, and spectra MRSA for
      detection of methicillin-resistant Staphylococcus aureus isolates in nasal
      surveillance cultures.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of hospital
      acquired and life-threatening infections. Active surveillance programs for MRSA
      utilize either molecular or culture-based methods. A prospective study was
      performed to compare the performance of selective and differential chromogenic
      media, BBL CHROMagar MRSA II (CMRSA II; BD Diagnostics, Sparks, MD), MRSASelect
      (Bio-Rad Laboratories, Redmond, WA), and Spectra MRSA (Remel, Lenexa, KS), for
      the detection of MRSA in nasal swab specimens. A total of 515 compliant remnant
      nasal swab specimens were sequentially used to inoculate BBL Trypticase soy agar
      with 5% sheep blood (TSA II) and each chromogenic medium. After 24 h of
      incubation, colony color reactions and morphology on chromogenic media were
      compared to suspicious colonies on nonselective TSA II. MRSA on TSA II was
      confirmed by Gram staining, a coagulase test, and a cefoxitin disk test. The
      overall prevalence of MRSA and methicillin-susceptible S. aureus (MSSA) on TSA II
      was 12.4% (64/515) and 9.7% (50/515), respectively. When each chromogenic medium
      was compared to the standard culture method, the sensitivity and specificity,
      respectively, were as follows: CMRSA II, 87.7% and 98.6%; MRSASelect, 89.0% and
      93.4%; and Spectra MRSA, 83.6% and 92.1%. The positive predictive values were
      highest for CMRSA II (91.4%), followed by MRSASelect (69.1%) and Spectra MRSA
      (63.5%). False-positive results on chromogenic media were mainly due to color
      interpretation. The negative predictive values for all three media were greater
      than 97%. In conclusion, CMRSA II gave the best overall results for detecting
      MRSA from nasal specimens.

PMID- 23135931
TI  - Genetic analysis of non-hydrogen sulfide-producing Salmonella enterica serovar
      typhimurium and S. enterica serovar infantis isolates in Japan.
AB  - Whole-genome sequencing of non-H(2)S-producing Salmonella enterica serovar
      Typhimurium and S. enterica serovar Infantis isolates from poultry meat revealed
      a nonsense mutation in the phsA thiosulfate reductase gene and carriage of a CMY
      2 beta-lactamase. The lack of production of H(2)S might lead to the incorrect
      identification of S. enterica isolates carrying antimicrobial resistance genes.

PMID- 23135932
TI  - Sensitivity and specificity of in situ hybridization for diagnosis of cutaneous
      infection by Leishmania infantum in dogs.
AB  - An accurate diagnosis of infection by Leishmania infantum in dogs is fundamental
      for the control of zoonotic visceral leishmaniasis (VL). Histopathology (HP) and
      immunohistochemistry (IHC) are frequently used for the histological diagnosis of
      L. infantum in dogs but have shown limited accuracy. To improve the sensitivity
      and specificity of the histological diagnosis of VL, we evaluated automated in
      situ hybridization (ISH) using a generic probe for Leishmania and a specific
      probe for L. infantum in surgical skin biopsy specimens of dogs. The ISH results
      were compared with those of HP and IHC, using parasitological culture as the
      reference standard. Skin samples from 51 dogs with cutaneous L. infantum
      infection and 51 noninfected dogs were randomly selected from samples of dogs
      from various cities in Brazil where canine VL is endemic. These samples were
      processed for parasitological culture, HP, IHC, and ISH using both probes. The
      sensitivities of ISH using the specific probe, ISH using the generic probe, IHC,
      and HP were, respectively, 74.5%, 70.6%, 69.5%, and 57.6%. The specificity of
      both ISH probes tested was 100%, and there was no cross-hybridization of the
      generic and specific probes with selected pathogenic fungi and protozoa. The
      specific probe discriminated L. infantum from the other species of Leishmania
      that infect dogs in the New World. ISH is highly sensitive and specific for the
      diagnosis of L. infantum in histologic samples of skin from infected dogs and can
      be used on routine biopsy material to make a diagnosis of leishmaniasis.

PMID- 23135933
TI  - Self-collection of foam nasal swabs for respiratory virus detection by PCR among
      immunocompetent subjects and hematopoietic cell transplant recipients.
AB  - Self-collected foam nasal swabs (NS) obtained after instillation of saline spray
      were compared with nasal washes from immunocompetent subjects during 146 upper
      respiratory infections (URIs); the sensitivities for reverse transcription (RT)
      PCR respiratory virus detection were 95% and 88%, respectively (P = 0.06). The
      sensitivities from NS collected with and without saline spray during 142 URIs
      from immunocompetent subjects were 96% and 86% (P = 0.004), respectively, and
      those from 140 URI samples from hematopoietic cell transplantation recipients
      were 88% and 85% (P = 0.56), respectively.

PMID- 23135934
TI  - Molecular characterization of methicillin-sensitive Staphylococcus aureus
      isolates from bacteremic patients in a Norwegian University Hospital.
AB  - Staphylococcus aureus bacteremia is common in both nosocomial and community
      settings, and the pathogenicity of the microbe depends upon a large repertoire of
      virulence factors. S. aureus bacteremia isolates (n = 126) were characterized
      using DNA microarrays. Clonal complexes 5, 8, 15, 30, and 45 accounted for 74.6%
      of the isolates. We identified geographical differences in dominating clones and
      toxin gene profiles. One isolate was methicillin resistant. Potential
      associations between age and genotype were detected.

PMID- 23135935
TI  - Assessment of real-time PCR assay for detection of Rickettsia spp. and Rickettsia
      rickettsii in banked clinical samples.
AB  - Two novel real-time PCR assays were developed for the detection of Rickettsia
      spp. One assay detects all tested Rickettsia spp.; the other is specific for
      Rickettsia rickettsii. Evaluation using DNA from human blood and tissue samples
      showed both assays to be more sensitive than nested PCR assays currently in use
      at the CDC.

PMID- 23135936
TI  - Carbapenem disks on MacConkey agar in screening methods for detection of
      carbapenem-resistant Gram-negative rods in stools.
AB  - Direct plating of simulated stool specimens on MacConkey agar (MCA) with 10-MUg
      ertapenem, meropenem, and imipenem disks allowed the establishment of optimal
      zone diameters for the screening of carbapenem-resistant Gram-negative rods
      (CRGNR) of <= 24 mm (ertapenem), <= 34 mm (meropenem), and <= 32 mm (imipenem).

PMID- 23135937
TI  - Genetic diversity of Burkholderia contaminans isolates from cystic fibrosis
      patients in Argentina.
AB  - A total of 120 Burkholderia cepacia complex isolates collected during 2004-2010
      from 66 patients in two cystic fibrosis reference centers in Argentina were
      analyzed. Burkholderia contaminans was the species most frequently recovered
      (57.6%), followed by Burkholderia cenocepacia (15%), a species distribution not
      reported so far. The recA-PCR-based techniques applied to the B. contaminans
      isolates revealed that 85% of the population carried the recA-ST-71 allele. Our
      results showed the utility of BOX-PCR genotyping in analyzing B. contaminans
      diversity. This approach allowed us to address clonal transmission during an
      outbreak and the genetic changes occurring in infecting bacteria over the course
      of chronic infection.

PMID- 23135938
TI  - Sonication versus vortexing of implants for diagnosis of prosthetic joint
      infection.
AB  - Biofilm removal efficacy of vortexing alone was compared with the standard
      vortexing-sonication procedure. Among 135 removed prostheses, 35 were diagnosed
      with infection and 100 with aseptic failure. At a cutoff of >= 50 CFU/ml,
      sonication was more sensitive than vortexing (60% versus 40%, P = 0.151), while
      the specificity was 99% for both methods.

PMID- 23135939
TI  - Diversification of clonal complex 5 methicillin-resistant Staphylococcus aureus
      strains (Rhine-Hesse clone) within Germany.
AB  - Since 1995, a methicillin-resistant Staphylococcus aureus (MRSA) clone has spread
      in southern Germany. The strain was assigned to the Rhine-Hesse pulsed-field gel
      electrophoresis (PFGE) type by the staphylococcal reference center and was highly
      similar to epidemic clones known to belong to clonal complex 5 (CC5; USA100)
      based on multilocus sequence typing (MLST). Here we analyzed a defined collection
      of strains assigned to the Rhine-Hesse/USA100 PFGE type. Using sequence-based
      typing methods (MLST, spa), the isolates were divided into two distinct clusters,
      ST5 and its single-locus variant ST225. These two lineages are not
      distinguishable by PFGE or phage typing. Most of the ST5 isolates were derived
      from patients and volunteers from the Tubingen area in southwest Germany, whereas
      the ST225 isolates were mostly from other locations in Germany. The locally
      restricted ST5 isolates were shown to contain different SSCmec islands and
      exhibited different antibiotic resistance profiles. In contrast, the ST225
      isolates form a highly homogenous group and are emerging all over Germany. The
      two lineages are clearly distinguishable by their phage content and spa type: ST5
      strains from Tubingen are characterized by a Sa7int phage that carries the
      virulence gene sak, which codes for staphylokinase, and ST225 isolates are
      characterized by a Sa1int phage. In conclusion, based on sequence typing and
      phage content, CC5 strains can be subdivided into two distinct lineages with
      different epidemicities.

PMID- 23135940
TI  - Quantitative fecal lactoferrin in toxin-positive and toxin-negative Clostridium
      difficile specimens.
AB  - Quantitative fecal lactoferrin was measured in 112 patients tested for toxigenic
      Clostridium difficile using glutamate dehydrogenase (GDH) and toxin immunoassays
      combined with tcdB PCR. Lactoferrin levels were higher in the GDH-positive/toxin
      positive group (79 MUg/ml) than in the GDH-positive/toxin-negative/PCR-positive
      (21 MUg/ml) and the GDH-negative groups (13 MUg/ml). Differences in fecal
      lactoferrin levels suggest variable presence or severity of C. difficile
      infection among toxin-positive and toxin-negative patients.

PMID- 23135941
TI  - Comparative drug resistance of Mycobacterium abscessus and M. chelonae isolates
      from patients with and without cystic fibrosis in the United Kingdom.
AB  - The isolation of rapidly growing mycobacteria (RGM), particularly Mycobacterium
      abscessus, from individuals with cystic fibrosis (CF) is associated with poor
      clinical outcome due to broad drug resistance and the difficulty of eradicating
      the organisms. Susceptibility testing is recommended to guide therapy. A disc
      diffusion method is used in the United Kingdom, whereas in the United States, the
      CLSI (Clinical and Laboratory Standards Institute) recommends the broth dilution
      method. The purpose of this study was to investigate whether the two methods
      produced comparable drug resistance profiles and to test the hypotheses that the
      disc diffusion method overscores resistance and that isolates of M. abscessus/M.
      chelonae from CF patients are more likely than those from non-CF patients to show
      drug resistance, as a result of CF patients' greater exposure to antibiotic
      therapy. A total of 82 isolates (58 M. abscessus and 24 M. chelonae isolates)
      were tested blindly against 15 antimicrobials by broth dilution and the disc
      diffusion method. Isolates tested by the broth microdilution showed high levels
      of resistance; susceptibility to amikacin, clarithromycin, tobramycin (only in M.
      chelonae), and cefoxitin (only in M. abscessus) was shown. Tigecycline results
      varied widely depending on which breakpoint was used. Agreement between methods
      for a few drugs (e.g., cefoxitin and amikacin) was poor. Although there were drug
      resistance differences between CF and non-CF isolates, these did not reach
      statistical significance. The CLSI method provided more robust breakpoints,
      standardization, and reproducibility. An analysis of the implementation of the
      CLSI method demonstrated ease of use and similar drug resistance findings for the
      two species.

PMID- 23135942
TI  - Characterization of a Tsukamurella pseudo-outbreak by phenotypic tests, 16S rRNA
      sequencing, pulsed-field gel electrophoresis, and metabolic footprinting.
AB  - We report a pseudo-outbreak of Tsukamurella due to improperly wrapped scissors
      used for processing of tissue specimens. A polyphasic approach, involving
      biochemical, genetic, and metabolomic techniques, was used in the laboratory
      investigation. This report highlights that early recognition of pseudo-outbreaks
      is important in preventing unnecessary and incorrect treatment of patients.

PMID- 23135943
TI  - Failure of PCR-Based IS6110 analysis to detect vertebral spondylodiscitis caused
      by Mycobacterium bovis.
AB  - Mycobacterium bovis is responsible for a zoonosis originating in cattle. We
      report a case of a man with vertebral spondylodiscitis caused by Mycobacterium
      bovis. Diagnosis was complicated because of the lack of IS6110. These strains are
      rare, but microbiologists should be aware of their existence.

PMID- 23135944
TI  - Detection of oxacillin-susceptible mecA-positive Staphylococcus aureus isolates
      by use of chromogenic medium MRSA ID.
AB  - Reports of oxacillin-susceptible mecA-positive Staphylococcus aureus strains are
      on the rise. Because of their susceptibility to oxacillin and cefoxitin, it is
      very difficult to detect them by using routine phenotypic methods. We describe
      two such isolates that were detected by chromogenic medium and confirmed by
      characterization of the mecA gene element.

PMID- 23135945
TI  - Impact of strain typing methods on assessment of relationship between paired
      nares and wound isolates of methicillin-resistant Staphylococcus aureus.
AB  - The anterior nares are the site of choice for the Veterans Administration
      methicillin-resistant Staphylococcus aureus (MRSA) surveillance program; however,
      a correlation between nares colonization and concomitant wound infections has not
      been well established. The purpose of this study was 3-fold: to determine the
      relatedness of MRSA isolates from 40 paired wound and nares specimens by four
      different strain typing methods, to determine concordance of typing methods, and
      to establish a baseline of MRSA types at this medical center. Isolates were typed
      by repetitive PCR (rep-PCR) (DiversiLab System; DL) and SpectraCell Raman
      analysis (SCRA) (commercially available methods that can be performed within a
      clinical lab), pulsed-field gel electrophoresis (PFGE), and an antibiotic
      susceptibility profile (AB). Whole-genome optical mapping (WGM) (OpGen, Inc.) was
      performed on selected isolates. All methods agreed that 26 pairs were
      indistinguishable and four pairs were different. Discrepant results were as
      follows: 4 where only SCRA was discordant, 3 where only AB was discordant, 2
      where both DL and AB were discordant, and 1 where both DL and SCRA were
      discordant. All WGM agreed with PFGE. After discrepancy resolution, 80% of the
      pairs were indistinguishable and 20% were different. A total of 56% of nares
      results were nonpredictive if negative nares and positive wound cultures are
      included. Methods agreed 85 to 93% of the time; however, congruence of isolates
      to a clade was lower. Baseline analysis of types showed that 15 pairs were unique
      to single patients (30 strains, 38%; 47% of the matching pairs). Twenty-five
      strains (30%) represented a single clade identical by PFGE, SCRA, and DL,
      decreasing specificity. Typing method and institutional type frequency are
      important in assessing MRSA strain relatedness.

PMID- 23135946
TI  - Public health value of next-generation DNA sequencing of enterohemorrhagic
      Escherichia coli isolates from an outbreak.
AB  - In 2009, an outbreak of enterohemorrhagic Escherichia coli (EHEC) on an open farm
      infected 93 persons, and approximately 22% of these individuals developed
      hemolytic-uremic syndrome (HUS). Genome sequencing was used to investigate
      outbreak-derived animal and human EHEC isolates. Phylogeny based on the whole
      genome sequence was used to place outbreak isolates in the context of the overall
      E. coli species and the O157:H7 sequence type 11 (ST11) subgroup. Four
      informative single nucleotide polymorphisms (SNPs) were identified and used to
      design an assay to type 122 other outbreak isolates. The SNP phylogeny
      demonstrated that the outbreak strain was from a lineage distinct from previously
      reported O157:H7 ST11 EHEC and was not a member of the hypervirulent clade 8. The
      strain harbored determinants for two Stx2 verotoxins and other putative virulence
      factors. When linked to the epidemiological information, the sequence data
      indicate that gross contamination of a single outbreak strain occurred across the
      farm prior to the first clinical report of HUS. The most likely explanation for
      these results is that a single successful strain of EHEC spread from a single
      introduction through the farm by clonal expansion and that contamination of the
      environment (including the possible colonization of several animals) led
      ultimately to human cases.

PMID- 23135947
TI  - Colonization dynamics of antibiotic-resistant coagulase-negative Staphylococci in
      neonates.
AB  - Coagulase-negative staphylococci (CoNS) isolated in neonatal late-onset sepsis
      are often antibiotic resistant. We analyzed CoNS from skin and feces of neonates
      during hospitalization. Antibiotic resistance of skin isolates increased during
      hospitalization, especially in Staphylococcus haemolyticus. Staphylococcus
      warneri showed low antibiotic resistance. Our data suggest that different CoNS
      species may play distinct roles in colonization.

PMID- 23135948
TI  - Use of rapid diagnostic tests for diagnosis of malaria in the United States.

PMID- 23135949
TI  - Clinical application of a multiplex real-time PCR assay for simultaneous
      detection of Legionella species, Legionella pneumophila, and Legionella
      pneumophila serogroup 1.
AB  - We developed a single-tube multiplex real-time PCR assay capable of
      simultaneously detecting and discriminating Legionella spp., Legionella
      pneumophila, and Legionella pneumophila serogroup 1 in primary specimens.
      Evaluation of 21 clinical specimens and 115 clinical isolates demonstrated this
      assay to be a rapid, high-throughput diagnostic test with 100% specificity that
      may aid during legionellosis outbreaks and epidemiologic investigations.

PMID- 23135950
TI  - Introduction to "Synovitis--an inflammation of joints destroying the bone".

PMID- 23135951
TI  - Mechanical and functional properties of epothilone-stabilized microtubules.
AB  - Using a suite of biophysical tools, we assess the mechanical, structural, and
      functional properties of microtubules (MTs) stabilized by the chemotherapeutic
      compounds epothilone-A, epothilone-B, and taxol in vitro. We demonstrate that MTs
      stabilized by epothilone-A or epothilone-B are competent to bind tau proteins and
      support kinesin translocation. Kinesin speed is sensitive not only to the type of
      small molecule stabilizer used but also to the presence of the essential MT
      associated protein tau. Epothilone-stabilized MTs are substantially less stiff
      than taxol-stabilized MTs. The addition of tau proteins to MTs stabilized by
      either epothilone compound or taxol further reduces stiffness. Taken together,
      these results suggest that small molecule stabilizers do not simply stabilize a
      "native" MT structure, but rather they modulate the structure, function, and
      mechanics of the MTs they bind. This may have important consequences to the
      therapeutic use of these agents in cancer chemotherapies.

PMID- 23135952
TI  - Microfluidic devices for high-throughput proteome analyses.
AB  - Over the last decades, microfabricated bioanalytical platforms have gained
      enormous interest due to their potential to revolutionize biological analytics.
      Their popularity is based on several key properties, such as high flexibility of
      design, low sample consumption, rapid analysis time, and minimization of manual
      handling steps, which are of interest for proteomics analyses. An ideal totally
      integrated chip-based microfluidic device could allow rapid automated workflows
      starting from cell cultivation and ending with MS-based proteome analysis. By
      reducing or eliminating sample handling and transfer steps and increasing the
      throughput of analyses these workflows would dramatically improve the
      reliability, reproducibility, and throughput of proteomic investigations. While
      these complete devices do not exist for routine use yet, many improvements have
      been made in the translation of proteomic sample handling and separation steps
      into microfluidic formats. In this review, we will focus on recent developments
      and strategies to enable and integrate proteomic workflows into microfluidic
      devices.

PMID- 23135953
TI  - Etiology of insulin resistance in youth with type 2 diabetes.
AB  - Type 2 diabetes (T2DM), historically an adult disease, is now increasingly
      prevalent in obese youth. Poor diet and increased sedentary behavior contribute
      to the increasing rates of obesity in youth, yet not all obese children develop
      T2DM. In general, T2DM is characterized by both insulin resistance (IR) and
      pancreatic beta-cell insufficiency. In children, IR is related to elevated body
      mass index (BMI) and pubertal hormones, along with abnormal fat partitioning,
      elevated free fatty acids, inflammation, and/or mitochondrial dysfunction.
      Hyperglycemia and T2DM develop when the pancreas cannot match the increased
      insulin demands resulting from IR. Unique to youth, IR varies with stage of
      pubertal development, and some children may have resolution of hyperglycemia post
      puberty once the IR of puberty resolves. Further understanding of IR, the
      progression to T2DM in youth, and later outcomes as adults will help direct
      future therapies and interventions for youth at risk.

PMID- 23135954
TI  - Chromosome abnormalities in diffuse large B-cell lymphomas: analysis of 231
      Chinese patients.
AB  - Genome instability is a hallmark of cancer. Diffuse large B-cell lymphoma (DLBCL)
      is the most common form of non-Hodgkin lymphoma with high levels of chromosomal
      aberrations. The purpose of this study was to characterize chromosomal
      aberrations in Chinese DLBCL patients and to compare chromosomal abnormalities
      between germinal centre B-cell-like (GCB) and non-GCB subgroups. Fluorescence in
      situ hybridization, G-band cytogenetics and immunohistochemistry were performed
      in 231 cases of de novo DLBCL. We demonstrated that the rate of abnormal and
      complex karyotypes was 89.1% (139/156) and 92.8% (129/139), respectively. We
      found a total of 490 structural chromosomal aberrations, including 96 frequent
      and recurring structural alterations. Most importantly, we identified several
      rare or novel chromosomal alterations: eight gains (5, 13, 14q, 17, 19p, 20, 21p,
      Y), one loss (21) and three recurrent translocations [t(7;15)(q22;q22),
      t(3;20)(p24;q13.1), t(2;3)(q21;q25)]. Moreover, the frequent recurrent genomic
      imbalance between GCB and non-GCB subgroups was different. Finally, we discovered
      two cases of concurrent IGH-BCL6 and MYC rearrangements. The rate of abnormal
      karyotypes in DLBCL patients of Chinese descent was similar to that of Western
      countries, but some common karyotypes were different, as were the abnormal
      karyotypes of GCB and non-GCB subgroups. Our discovery of rare and novel abnormal
      karyotypes may represent unique chromosomal alterations in Chinese DLBCL
      patients.

PMID- 23135955
TI  - Chondrogenic differentiation of bone marrow concentrate grown onto a hylauronan
      scaffold: rationale for its use in the treatment of cartilage lesions.
AB  - Bone marrow is one of the best characterized stem cell microenvironment that
      contains Mesenchymal Stem Cells (MSCs). MSCs have been indicated as a new option
      for regenerative medicine because of their ability to differentiate into bone,
      cartilage and adipose tissues. However, in vitro-cultivation of MSCs could be
      associated with some shortcomings such as the possibility of the de
      differentiation or reprogramming of the cells and the increase of the risk of
      infection and contaminations. To overcome these problems, a new approach is
      represented by the use of Bone Marrow Concentrate (BMC). This enables the implant
      of a cell population surrounded by its microenvironment preventing all the
      complications related to the in vitro-culture. Moreover, the cells within the
      bone marrow niche are able to regulate stem cell behavior through direct physical
      contact and by secreting paracrine factors. The aim of this study was to
      investigate the phenotype of cells within BMC and their ability to differentiate
      into chondrogenic lineage once seeded onto a hyaluronan-based scaffold (Hyaff-11)
      already used in clinic. The chondrogenic potential of BMC has been evaluated by
      means of morphological, histological, immunohistochemical and molecular analyses.
      The data obtained with the current study demonstrated that cells within BMC grown
      onto HYAFF-11 are able to differentiate into chondrogenic sense by the expression
      and production of specific extracellular molecules. These findings support the
      use of BMC in clinic for the repair of cartilage lesions allowing its
      transplantation in a "One Step" procedure.

PMID- 23135956
TI  - Wavelength tunable CdSe nanowire lasers based on the absorption-emission
      absorption process.

PMID- 23135957
TI  - E-cadherin interactions are required for Langerhans cell differentiation.
AB  - Human skin contains the following two distinct DC subsets: (i) Langerhans cells
      (LCs), expressing Langerin but not DC-specific intercellular adhesion molecule-3
      grabbing nonintegrin (DC-SIGN), are predominantly localized in the epidermis; and
      (ii) dermal DCs, expressing DC-SIGN but not Langerin, are observed mainly in the
      dermis. It is not known whether localization in the epidermis provides cues for
      LC differentiation. Here, we show that E-cadherin expressed by epidermal
      keratinocytes (KCs) is crucial for differentiation of LCs. Monocytes
      differentiated into LC-like cells in presence of IL-4, GM-CSF, and TGF-beta1.
      However, these LC-like cells expressed not only Langerin but also DC-SIGN.
      Notably, co-culturing of these LC-like cells with KCs expressing E-cadherin or
      recombinant E-cadherin strongly decreased expression of DC-SIGN and further
      induced a phenotype similar to purified epidermal LCs. Moreover, pretreatment of
      LC-like cells with anti-E-cadherin-specific antibody completely abolished their
      Langerin expression, indicating the requirement of E-cadherin-E-cadherin
      interactions for the differentiation into Langerin(+)  cells. These findings
      suggest that E-cadherin expressed by KCs provide environmental cues that induce
      differentiation of LCs in the epidermis.

PMID- 23135958
TI  - Synthesis and characterization of [M2(N=CtBu2)5]- (M=Mn, Fe, Co): metal ketimide
      complexes with strong metal-metal interactions.

PMID- 23135959
TI  - Sport climbing from a medical point of view.
AB  - Rock climbing, sport climbing and bouldering are highly popular new sport
      disciplines. An increasing number of indoor climbing gyms throughout the country
      offer the possibility to perform the sport regularly independently from the
      weather. As a result a variety of new pathologies like the closed flexor tendon
      pulley rupture of the finger and syndromes caused by overuse mainly in the upper
      extremity have appeared and should be familiar to physicians and therapists
      working in the field of sports medicine. An overview of the most common and most
      specific climbing related injuries as well as their diagnosis and treatment
      options with a focus on the upper extremity are presented.

PMID- 23135960
TI  - Endoscopy teams' judgment of discomfort among patients undergoing colonoscopy:
      "How bad was it really?".
AB  - QUESTIONS UNDER STUDY / PRINCIPLES: Colonoscopies are complex procedures that
      depend greatly on the patient's cooperation and on the correct judgment of a
      tolerable amount of discomfort by the endoscopy team, even in sedated patients.
      Little is known regarding the accuracy of the patient comfort level assessments
      made by medical staff. METHODS: We prospectively evaluated the degree of
      agreement between the assessments made by the endoscopists and endoscopy nurses
      and the assessments made by patients regarding their comfort level during the
      procedure. A total of 222 patients scheduled for routine colonoscopies assessed
      their preprocedural anxiety and the tolerability of the procedure. Endoscopists
      and nurses assessed the difficulty of the examination and the patient's level of
      discomfort. Assessments were performed using a 100-mm VAS. RESULTS: Overall,
      patients rated the procedure as tolerable. For 12% (27/222) of the patients, the
      examination was less tolerable (VAS >50 mm). The patients' judgment of
      tolerability was not related to the initial level of anxiety (r = 0.15). The
      scores of the endoscopists and nurses were better correlated with each other (r =
      0.58) than with the patients' self-assessments (r = 0.37 and 0.35, respectively).
      Both endoscopists and nurses tended to overestimate the patients' discomfort.
      However, in 9% (19/222) of cases, the level of patient discomfort was
      considerably underestimated by at least one member of the team. CONCLUSION: Our
      study shows that the estimation of a patient's discomfort during a colonoscopy is
      difficult and that the comfort level may not be accurately determined in a
      considerable number of patients, including sedated patients.

PMID- 23135961
TI  - Highly enantioselective imine hydrogenation catalyzed by ruthenium phosphane
      phosphite diamine complexes.
AB  - Mildly does it: a highly enantioselective catalyst for the hydrogenation of N
      aryl imines is described. This catalyst offers practical advantages because it
      operates under very mild conditions and is based on an Ru complex with a diamine
      as the sole chiral ligand.

PMID- 23135962
TI  - CD14 and IL6 polymorphisms are associated with a pro-atherogenic profile in young
      adults with acute myocardial infarction.
AB  - This study investigated the relationship of polymorphisms in genes encoding CD14,
      IL-6 and TLR4 with metabolic, inflammatory and endothelial markers in young
      adults with acute myocardial infarction (AMI). Glucose, lipids, nitrate and
      inflammatory markers, flow mediated vasodilatation (FMV) and flow mediated by
      nitrate (FMN) were evaluated in 102 AMI and 108 non-AMI (control group) young
      individuals (<45 years). CD14 -260C>T (rs2569190), IL6 -174G>C (rs1800795) and
      TLR4 c.896A>G (rs4986790) and TLR4 c.1196C>T (rs4986791) polymorphisms were
      analyzed by PCR-RFLP. Minor allele frequencies of CD14, IL6 and TLR4
      polymorphisms were similar between AMI and control groups (p > 0.05). In AMI
      group, individuals carrying IL6 -174CC genotype had higher serum triglycerides,
      VLDL cholesterol and glucose compared to the IL6 -174GG/GC genotype carriers (p <
      0.05). Multiple logistic analysis showed that IL6 -174CC genotype carriers had
      increased risk for hyperglycemia (>5.77 mmol/l) [OR: 6.75, 95 % CI: 1.80-24.40, p
      = 0.004] and hypertriglyceridemia (>2.68 mmol/l) [OR: 3.00, 95 % CI: 1.00-9.00, p
      = 0.043]. Moreover, CD14 -260TT genotype was associated with reduced serum HDL
      cholesterol [OR: 3.10, 95 % CI: 1.00-9.01, p = 0.044] and apolipoprotein AI [OR:
      3.20, 95 % CI: 1.00-9.70, p = 0.038] in AMI group. Relationship between CD14 and
      IL6 variants and altered inflammatory and endothelial (nitrate, FMV and FMN)
      markers was not found in both AMI and control groups. The IL6 -174G>C and CD14 
      260C>T polymorphisms are likely to be associated with a pro-atherogenic profile
      but not with increased inflammatory markers and endothelial dysfunction in young
      AMI patients. 

PMID- 23135963
TI  - Inhibition of T cell protein tyrosine phosphatase enhances interleukin-18
      dependent hematopoietic stem cell expansion.
AB  - The clinical application of hematopoietic progenitor cell-based therapies for the
      treatment of hematological diseases is hindered by current protocols, which are
      cumbersome and have limited efficacy to augment the progenitor cell pool. We
      report that inhibition of T-cell protein tyrosine phosphatase (TC-PTP), an enzyme
      involved in the regulation of cytokine signaling, through gene knockout results
      in a ninefold increase in the number of hematopoietic progenitors in murine bone
      marrow (BM). This effect could be reproduced using a short (48 hours) treatment
      with a pharmacological inhibitor of TC-PTP in murine BM, as well as in human BM,
      peripheral blood, and cord blood. We also demonstrate that the ex vivo use of TC
      PTP inhibitor only provides a temporary effect on stem cells and did not alter
      their capacity to reconstitute all hematopoietic components in vivo. We establish
      that one of the mechanisms whereby inhibition of TC-PTP mediates its effects
      involves the interleukin-18 (IL-18) signaling pathway, leading to increased
      production of IL-12 and interferon-gamma by progenitor cells. Together, our
      results reveal a previously unrecognized role for IL-18 in contributing to the
      augmentation of the stem cell pool and provide a novel and simple method to
      rapidly expand progenitor cells from a variety of sources using a pharmacological
      compound.

PMID- 23135964
TI  - Upregulation of Bcl-2 in nasal polyps from patients with cystic fibrosis.
AB  - BACKGROUND: Nasal polyps in patients with cystic fibrosis (CF) are believed to be
      phenotypically different than polyps affecting non-CF patients. The aim of this
      study was to investigate differences in cell cycle regulatory mechanisms between
      these 2 groups. In this prospective study at a tertiary care academic medical
      center, multiple techniques were used to confirm the upregulation of
      antiapoptotic Bcl-2 family proteins in CF polyps. METHODS: Nasal polyps were
      prospectively obtained from CF and non-CF patients. The Sigma Panorama Protein
      Microarray for Cell Signaling was used to identify differences in protein
      expression between the 2 polyp groups. Western blot analysis confirmed altered
      expression of a subset of these proteins. Immunohistochemical staining was
      performed on archived tissue to further investigate B-cell lymphoma 2 protein
      (Bcl-2) expression. Following review by a pathologist, slides were digitized
      using an AperioTM ScanScope XT system and staining intensity was quantified with
      the Positive Pixel Count algorithm. The mean staining intensity for each polyp
      group was compared. RESULTS: The protein microarray suggested a greater than 2
      fold upregulation of Bcl-xl in CF polyps relative to non-CF polyps. Western blot
      analysis confirmed the upregulation in CF polyps of Bcl-2, a more commonly
      studied protein analog of Bcl-xl. The CF polyp group was noted to have a higher
      quantitative intensity of immunohistochemical staining for Bcl-2 compared to the
      non-CF group (p < 0.05). CONCLUSION: Through multiple modalities of protein
      investigation, we have demonstrated an upregulation of Bcl-2 family proteins in
      CF polyps relative to polyps from non-CF patients.

PMID- 23135965
TI  - Effect of processing route on the surface properties of amorphous indomethacin
      measured by inverse gas chromatography.
AB  - The aim of this study was to investigate the effect of processing route (i.e.,
      quench cooling and ball milling) on the surface energy heterogeneity and surface
      chemistry of indomethacin (IMC). Recently developed inverse gas chromatography
      (IGC) methodology at finite concentrations was employed to determine the surface
      energy distributions of crystalline, quench cooled and milled IMC samples.
      Surface properties of crystalline and processed IMC were measurably different as
      determined by the IGC and other conventional characterization techniques:
      differential scanning calorimetry and powder X-ray diffraction. Quench cooled IMC
      was in fully amorphous form. Milled IMC showed no amorphous character by
      calorimetric or X-ray diffraction studies. It was demonstrated that both
      processed IMC samples were energetically more active than the crystalline IMC. In
      particular, milled IMC exhibited a relatively higher dispersive surface energy
      and higher surface basicity (electron donor capability). This may be attributed
      to the creation of surface defect sites or exposure of higher energy crystal
      facets during the milling process. This study confirms that processing route has
      notable influence on the surface energy distribution and surface acid-base
      character. IGC was demonstrated as a powerful technique for investigating surface
      properties of real-world, heterogeneous pharmaceutical materials.

PMID- 23135966
TI  - Development of bilayer floating tablet of amoxicillin and Aloe vera gel powder
      for treatment of gastric ulcers.
AB  - Usual treatment for Helicobacter pylori-induced peptic ulcer includes a 'triple
      therapy' consisting of two antibiotics (amoxicillin and clarithromycin) and a
      proton pump inhibitor (omeprazole). The objective of this project work was
      defined with a view to retain the drug in stomach for better antiulcer activity
      and substituting one of the synthetic drugs in this therapy with a herbal
      alternative. Hence, aim of the present work was to design and develop a bilayer
      floating tablet of amoxicillin and Aloe vera gel powder for the treatment of
      peptic ulcer. A. vera gel powder is used for its cytoprotective action. Bilayer
      floating tablets were prepared by applying direct compression technique. The
      proportion of sodium bicarbonate and citric acid was adjusted to get the least
      possible lag time with good matrix integrity and total floating time. Polymer
      concentration was adjusted to get the maximum release in 8 h. The formulation was
      developed using hydroxypropyl methyl cellulose (HPMC) K4M and HPMC K100M in a
      ratio of 85:15 along with 1:4 ratio of effervescent agents was found to give
      floating lag time of less than 1 min with total floating time of more than 8 h
      and 97.0% drug release in 8 h. In vivo study in rats meets the requirement of
      antiulcer activity for bilayer tablet in comparison to single amoxicillin as
      standard.

PMID- 23135967
TI  - Genetic testing in the contemporary diagnosis of cardiomyopathy.
AB  - The heritable cardiomyopathies are relatively common conditions that can lead to
      heart failure and sudden cardiac death. Family history collection, genetic
      testing and genetic counseling are recommended for these patients and families in
      multiple practice guidelines and consensus statements. Research discoveries and
      rapidly dropping costs of DNA sequencing technologies have resulted in the
      availability of multiple cardiomyopathy genetic testing panels. Genetic testing
      not only helps in determining the underlying etiology of idiopathic and familial
      cardiomyopathies, but is also a powerful tool in the determination of which
      relatives are at-risk and which are not. Both pre- and post-test genetic
      counseling is an imperative component of genetic testing, as there are many
      benefits and limitations of genetic testing that need discussed with each patient
      undergoing this process.

PMID- 23135968
TI  - Controlled synthesis of large-scale, uniform, vertically standing graphene for
      high-performance field emitters.
AB  - Large-scale, uniform, vertically standing graphene with atomically thin edges are
      controllably synthesized on copper foil using a microwave-plasma chemical vapor
      deposition system. A growth mechanism for this system is proposed. This film
      shows excellent field-emission properties, with low turn-on field of 1.3 V MUm(
      1) , low threshold field of 3.0 V MUm(-1)  and a large field-enhancement factor
      more than 10 000.

PMID- 23135969
TI  - Up-regulation of sarcoplasmic reticulum Ca(2+) uptake leads to cardiac
      hypertrophy, contractile dysfunction and early mortality in mice deficient in
      CASQ2.
AB  - AIMS: Although aberrant Ca(2+) release (i.e. Ca(2+) 'leak') from the sarcoplasmic
      reticulum (SR) through cardiac ryanodine receptors (RyR2) is linked to heart
      failure (HF), it remains unknown whether and under what conditions SR-derived
      Ca(2+) can actually cause HF. We tested the hypothesis that combining
      dysregulated RyR2 function with facilitated Ca(2+) uptake into SR will exacerbate
      abnormal SR Ca(2+) release and induce HF. We also examined the mechanisms for
      these alterations. METHODS AND RESULTS: We crossbred mice deficient in expression
      of cardiac calsequestrin (CASQ2) with mice overexpressing the skeletal muscle
      isoform of SR Ca(2+)ATPase (SERCA1a). The new double-mutant strains displayed
      early mortality, congestive HF with left ventricular dilated hypertrophy, and
      decreased ejection fraction. Intact right ventricular muscle preparations from
      double-mutant mice preserved normal systolic contractile force but were
      susceptible to spontaneous contractions. Double-mutant cardiomyocytes while
      preserving normal amplitude of systolic Ca(2+) transients displayed marked
      disturbances in diastolic Ca(2+) handling in the form of multiple, periodic
      Ca(2+) waves and wavelets. Dysregulated myocyte Ca(2+) handling and structural
      and functional cardiac pathology in double-mutant mice were associated with
      increased rate of apoptotic cell death. Qualitatively similar results were
      obtained in a hybrid strain created by crossing CASQ2 knockout mice with mice
      deficient in phospholamban. CONCLUSION: We demonstrate that enhanced SR Ca(2+)
      uptake combined with dysregulated RyR2s results in sustained diastolic Ca(2+)
      release causing apoptosis, dilated cardiomyopathy, and early mortality. Our data
      also suggest that up-regulation of SERCA activity must be advocated with caution
      as a therapy for HF in the context of abnormal RyR2 function.

PMID- 23135970
TI  - Quantitative proteomic analysis to decipher the differential apoptotic response
      of bortezomib-treated APL cells before and after retinoic acid differentiation
      reveals involvement of protein toxicity mechanisms.
AB  - The ubiquitin-proteasome system allows the targeted degradation of proteins and
      plays a critical role in the regulation of many cellular processes. Proteasome
      inhibition is a recent antitumor therapeutic strategy and bortezomib was the
      first proteasome inhibitor approved for clinical use. In this study, we used the
      NB4 cell line to investigate the effects of bortezomib toward acute promyelocytic
      leukemia cells before and after retinoic acid-induced differentiation. We showed
      that apoptosis level after bortezomib treatment is higher in NB4 cells than in
      differentiated NB4 cells. To compare early protein variations upon bortezomib
      treatment in both NB4 cell populations, we performed a quantitative proteomic
      analysis based on iTRAQ peptide labeling followed by data analysis with in-house
      developed scripts. This strategy revealed the regulation of 14 proteins
      principally involved in protein stress response and apoptosis in NB4 cells after
      proteasome inhibition. Altogether, our results suggest that the differential
      level of apoptosis induced by bortezomib treatment in both NB4 cell populations
      could result from distinct protein toxicity level.

PMID- 23135972
TI  - Cooperative catalysis by iridium complexes with a bipyridonate ligand: versatile
      dehydrogenative oxidation of alcohols and reversible dehydrogenation
      hydrogenation between 2-propanol and acetone.

PMID- 23135973
TI  - Endoscopic removal of a fractured partially covered Evolution esophageal stent.

PMID- 23135974
TI  - Successful treatment with an over-the-scope clip of Dieulafoy's gastric lesion
      resistant to conventional endoscopic treatment.

PMID- 23135975
TI  - Aberrant antibody affinity selection in SHIP-deficient B cells.
AB  - The strength of the Ag receptor signal influences development and negative
      selection of B cells, and it might also affect B-cell survival and selection in
      the GC. Here, we have used mice with B-cell-specific deletion of the 5'-inositol
      phosphatase SHIP as a model to study affinity selection in cells that are
      hyperresponsive to Ag and cytokine receptor stimulation. In the absence of SHIP,
      B cells have lower thresholds for Ag- and interferon (IFN)-induced activation,
      resulting in augmented negative selection in the BM and enhanced B-cell
      maturation in the periphery. Despite a tendency to spontaneously downregulate
      surface IgM expression, SHIP deficiency does not alter anergy induction in
      response to soluble hen-egg lysozyme Ag in the MDA4 transgenic model. SHIP
      deficient B cells spontaneously produce isotype-switched antibodies; however,
      they are poor responders in immunization and infection models. While SHIP
      deficient B cells form GCs and undergo mutation, they are not properly selected
      for high-affinity antibodies. These results illustrate the importance of negative
      regulation of B-cell responses, as lower thresholds for B-cell activation promote
      survival of low affinity and deleterious receptors to the detriment of optimal Ab
      affinity maturation.

PMID- 23135976
TI  - Effect of bispectral index monitoring on extubation time and analgesic
      consumption in abdominal surgery: a randomised clinical trial.
AB  - PRINCIPLES: The aim of this study was to investigate the effect of bispectral
      index (BIS) monitoring on intra-operative anaesthesia consumption and extubation
      time. DESIGN: Randomised controlled study. METHODS: The study included 45
      patients undergoing major abdominal surgery under general anaesthesia in a six
      month period (February - July 2011), aged 18 years or older, and classified as
      ASA (American Society of Anaesthesiologists) physical status II or III. Patients
      were randomly assigned to receive BIS-guided anaesthesia or routine anaesthesia
      care as a non BIS-guided group. At the induction of anaesthesia, and during the
      operation the following parameters were continuously recorded: BIS level, heart
      rate (HR), systolic blood pressure (sBP), end-tidal CO2 (etCO2).Operation time
      and time to extubation were also recorded. On the first post-operative day all
      patients were visited and interviewed about intra-operative recall. RESULTS: BIS
      levels in the non BIS-guided group were significantly lower from 30 minutes
      further to the end of the operation, compared to the BIS-guided group (p <0.05).
      Time to extubation was significantly shorter in the BIS-guided group (17.5 min
      vs. 75 min, p <0.001). There were no statistically significant differences in the
      required amounts of anaesthetics. In the post-operative interview, none of the
      patients reported an episode of intra-operative awareness. CONCLUSION: Guiding
      anaesthesia according to BIS level will result in significantly faster recovery
      after anaesthesia. The investigation was registered on ClinicalTrials.gov
      (NCT01470898).

PMID- 23135977
TI  - Impact of transcatheter aortic valve implantation or surgical aortic valve
      replacement on right ventricular function--the reply.

PMID- 23135978
TI  - Osteoprotegerin improves risk detection by traditional cardiovascular risk
      factors and hsCRP.
AB  - OBJECTIVE: To evaluate the association of plasma osteoprotegerin (OPG) to
      hospitalisation for ischaemic heart disease (IHD), ischaemic stroke and all-cause
      mortality, and the effect of combining plasma OPG and high-sensitivity C-reactive
      protein (hsCRP). DESIGN: OPG and hsCRP concentrations were measured at baseline
      in a large Danish prospective community-based population study. SETTING: The 4th
      Copenhagen City Heart Study. PARTICIPANTS: 5863 men and women aged 20-95 were
      recruited from the general population. MAIN OUTCOME MEASURES: Combined end-point
      of IHD, ischaemic stroke or all-cause mortality. RESULTS: During a median follow
      up of 7.8 years (IQR 7.3-8.3), 1270 subjects (21.7%) reached the combined end
      point. A twofold increase in plasma OPG was a significant predictor of the
      combined end-point (univariable HR 1.85, 95% CI 1.75 to 1.96; p<0.001). In a
      multivariable Cox-regression model containing age, male sex, hypertension,
      diabetes, hypercholesterolaemia, present or former smoking, glomerular filtration
      rate, prior IHD, prior ischaemic stroke, hsCRP and plasma OPG, high
      concentrations of hsCRP and plasma OPG were independent predictors of the
      combined end-point. The two biomarkers interacted statistically (p<0.001).
      Compared to low hsCRP and low OPG (n=1927), either high hsCRP or high OPG
      (univariable HR 2.38, 95% CI 2.02 to 2.80, p<0.001; n=2816), or both high hsCRP
      and high OPG (univariable HR 5.13, 95% CI 4.29 to 6.13, p<0.001; n=775) conferred
      increased risk of the combined end-point. CONCLUSIONS: OPG is an independent
      predictor of the combined end-point of hospitalisation of IHD, ischaemic stroke
      and all-cause mortality. The combination of plasma OPG and hsCRP provides more
      prognostic information than the individual effect of the two biomarkers.

PMID- 23135979
TI  - Evaluating new diagnostic and prognostic biomarkers in cardiovascular disease.

PMID- 23135980
TI  - Beware of the embolus.

PMID- 23135981
TI  - Prevalence, molecular diagnosis and treatment of Mycoplasma conjunctivae isolated
      from infectious keratoconjunctivitis affected Lohi sheep maintained at Livestock
      Experiment Station, Bahadurnagar, Okara, Pakistan.
AB  - Mycoplasma conjunctivae are etiological agents of infectious keratoconjunctivitis
      (IKC), commonly known as pink-eye in domestic sheep, goats and other wild animals
      in many parts of the world. A few young Lohi lambs maintained at Livestock
      Experiment Station (LES), Bahadurnagar, Okara, Pakistan showed clinical signs and
      symptoms of conjunctivitis, keratitis, severe lacrimation and varying degree of
      blindness. During January to March, 2011, a total of 36 ocular swabs were
      collected from IKC affected animals and were processed for isolation,
      identification, and characterization of M. conjunctivae. Sixteen (44.44 %) out of
      36 samples showed turbidity in PPLO broth. Twelve (75 %) out of 16 broth samples
      showed colony growth on PPLO agar. All 16 (44.44 %) out of 36 turbid broth
      samples, 12 (75 %) out of 16 cultured on agar plate samples, and 21 (59 %) out of
      36 sheep ocular direct swab samples were found positive for M. conjunctivae
      through polymerase chain reaction test by using M. conjunctivae-specific primer
      pair McoF1 and McoR1 and detecting a 750 base pair fragment on agarose gel.
      Topical application of 0.5 % sterile solution of gentamycin (100 mg/ml) (Gentafar
      10 %, FARVET, Netherlands) proved suitable for the treatment of IKC in Lohi lambs
      as all clinical signs of IKC disappeared after 5 days of treatment with this
      antibiotic. This is the first report about the prevalence, molecular diagnosis,
      and treatment of M. conjunctivae in Lohi sheep affected with infectious
      keratoconjunctivitis at LES, Bahadurnagar, Okara, Pakistan.

PMID- 23135982
TI  - Estrus induction in anestrous mixed-breed goats using the "female-to-female
      effect".
AB  - A trial was conducted during the anestrous period in female goats to determine:
      (a) whether estrus can be induced in anestrous goats by administration of equine
      chorionic gonadotropic hormone (eCG) and PGF2alpha under pen conditions and (b)
      whether these sexually active female goats can elicit sexual arousal in sexually
      inactive bucks. One hundred and fifteen pluriparous, nonlactating mixed-breed
      female goats were randomly assigned to one of four treatment groups: (1)
      administration of a single dose of 240 IU of eCG, 50 MUg PGF2alpha i.m., and 25
      mg progesterone (P4) (eCG; n=30); (2) administration of P4 and exposure to female
      goats treated with eCG-PGF2alpha (P4; n=39); (3) administration of 0.5 ml saline
      and P4 (Sal; n=23); and (4) P4 plus exposure to female goats treated with saline
      (Con; n=23). After hormone administration, all goats were put together with adult
      sexually inactive bucks for 15 days. The percentage of goats in estrus during
      these 15 days was similar in eCG-treated animals and untreated animals exposed to
      the eCG animals (97 and 95%). Pregnancy rate was also similar (63 vs. 64%)
      between these two groups. eCG-treated goats exhibited estrus earlier (P<0.05)
      than the treated goats in contact with the eCG goats. Furthermore, eCG-treated
      goats had larger litters (1.9 +/- 0.2 vs. 1.6 +/- 0.1, P<0.05) than the untreated
      goats in contact with the eCG goats. These results show that fertile estrus can
      be induced in anestrous female goats by exposing them to female goats induced to
      estrus with eCG. This female-female interaction triggers the stimulation cycle
      leading to the sexual arousal of bucks.

PMID- 23135983
TI  - Investigation in early growth traits, litter size, and lamb survival in two
      Iranian fat-tailed sheep breeds.
AB  - In the present study, 1,635 lambing records of Ghezel (n=766) and Mehraban
      (n=869) breeds were used to evaluate the early growth traits, litter size, and
      lamb survival in sheep reared in Fars Province, southern Iran, during a 5-year
      long period. The least squares means (+/- SE) of lamb birth weight for Ghezel
      were 5.27 (+/- 0.22), 5.02 (+/- 0.22), and 3.98 (+/- 0.23) kg for single males,
      single females, and twin lambs, respectively; whereas, the corresponding values
      for Mehraban were 4.39 (+/- 0.18), 4.18 (+/- 0.18), and 3.50 (+/- 0.19) kg. The
      least squares means of pre-weaning lamb growth (gram per day) for Ghezel were 239
      (+/- 15), 218 (+/- 15), and 181 (+/- 16) for single males, single females, and
      twin lambs, respectively, and the corresponding values for Mehraban were 204 (+/-
      12), 187 (+/- 12), and 156 (+/- 13). Lambs from 2 year old ewes or younger were
      on average lighter at birth and at weaning and had a lower average daily gain
      than those from older ewes (P<0.05). The percentage of twin births increased from
      1.1 and 1.3 % for ewes aged <= 2 years to 19 and 12 % for those aged >= 6 years
      old in Ghezel and Mehraban, respectively (P<0.05). The mean pre-weaning lamb
      mortality was 7.1 and 4.1 % for Ghezel and Mehraban, respectively.

PMID- 23135984
TI  - Evaluation of five serological tests for the diagnosis of porcine brucellosis in
      French Polynesia.
AB  - Porcine brucellosis due to Brucella suis biovar 1 raises important issues for pig
      breeders in French Polynesia. In this region, the disease is enzootic, spreads
      silently and engenders economic losses in infected farms as well as sporadic
      human cases. While serological tests are essential in surveillance and control
      programmes of animal diseases, to date none of the available tests have been
      shown to be reliable enough to be used as a gold standard in routine individual
      diagnosis of porcine brucellosis. Few studies about the estimation of the
      sensitivity and the specificity of porcine brucellosis screening tests have been
      published, none of them dealing with French Polynesia. The studied population
      included 1,595 pigs from French Polynesia. Five tests were evaluated: Rose Bengal
      test, fluorescence polarisation assay, indirect ELISA, and two competitive ELISAs
      (C-ELISA). The sensitivity and the specificity of each test were estimated. C
      ELISA2 was the most sensitive test (Se C-ELISA2=0.954 [0.889; 0.992] 95%
      credibility interval (CrI)) while both C-ELISA and Rose Bengal test (RBT) were
      the most specific ones (Sp C-ELISA1=0.856 [0.806; 0.915] 95% CrI; Sp C
      ELISA2=0.849 [0.817; 0.879] 95% CrI; Sp RBT=0.853 [0.812; 0.898] 95% CrI).

PMID- 23135985
TI  - Effect of rice polishing and phytase supplementation in diets on productive
      behavior of broilers.
AB  - The addition of rice polishing (RP) and phytase enzyme to poultry diets was
      tested on 200 1-day-old broilers weighing 42 g. Birds were assigned to a
      completely random design with a 2 * 2 factorial arrangement with four treatments
      and five repetitions of ten birds each. The factors evaluated were RP level (0
      and 15%) and phytase (0 and 150 g/ton). The trial was divided in two phases of 21
      days each (42 days total). In phase 1, no treatment effects were observed
      (P>0.10) on poultry productive behavior. In the second phase (21 to 42 days) and
      on the total trial (1 to 42 days), there were no effects of the treatments on
      weight gain or feed intake (P>0.10). Feed conversion was affected by RP (P<0.01)
      but not by phytase addition (P>0.10). In conclusion, phytase did not affect
      broiler production with or without RP. Addition of 15 % RP in poultry diets
      represents an alternative to reduce feed costs.

PMID- 23135986
TI  - Investigation of the genetic diversity among native Turkish sheep breeds using
      mtDNA polymorphisms.
AB  - A total of 135 unrelated sheep from nine Turkish native sheep breeds (Daglic,
      Kivircik, Imroz, Chios, Morkaraman, Ivesi, Hemsin, Karayaka and Akkaraman) were
      investigated to determinate the maternal genetic diversity using a sequence of a
      531-bp segment of the mtDNA control region. Analysis of the mtDNA control region
      sequence revealed 63 haplotypes and 53 polymorphic sites. Haplotype diversity,
      nucleotide diversity and the average number of nucleotide differences were
      estimated to be 0.9496 +/- 0.011, 0.01407 +/- 0.00060 and 7.456, respectively.
      The sequence analysis also revealed high level of genetic diversity among the
      native Turkish breeds. These breeds were grouped into three major maternal
      haplogroups: A, B and C, with one animal belonging from the Akkaraman breed to
      the rare haplogroup E. Irregular shape of mismatch distribution of haplogroup C
      could be an indicator that haplogroup C may represent different haplogroups.
      Contrarily to previous studies carried out on Turkish native breeds, majority of
      animals grouped in haplogroup A in the present study. This result and the
      irregular shape of mismatch curve of haplogroup C indicate that genetic structure
      of Turkish native sheep breeds could be more complicated than it is thought.

PMID- 23135987
TI  - TEL (ETV6)-AML1 (RUNX1) initiates self-renewing fetal pro-B cells in association
      with a transcriptional program shared with embryonic stem cells in mice.
AB  - The initial steps involved in the pathogenesis of acute leukemia are poorly
      understood. The TEL-AML1 fusion gene usually arises before birth, producing a
      persistent and covert preleukemic clone that may convert to precursor B cell
      leukemia following the accumulation of secondary genetic "hits." Here, we show
      that TEL-AML1 can induce persistent self-renewing pro-B cells in mice. TEL-AML1+
      cells nevertheless differentiate terminally in the long term, providing a
      "window" period that may allow secondary genetic hits to accumulate and lead to
      leukemia. TEL-AML1-mediated self-renewal is associated with a transcriptional
      program shared with embryonic stem cells (ESCs), within which Mybl2, Tgif2, Pim2,
      and Hmgb3 are critical and sufficient components to establish self-renewing pro-B
      cells. We further show that TEL-AML1 increases the number of leukemia-initiating
      cells that are generated in collaboration with additional genetic hits, thus
      providing an overall basis for the development of novel therapeutic and
      preventive measures targeting the TEL-AML1-associated transcriptional program.

PMID- 23135988
TI  - Risk factors and outcomes for primary, revision, and modified Lothrop (Draf III)
      frontal sinus surgery.
AB  - BACKGROUND: The purpose of this level 4, retrospective cohort study was to detail
      the outcomes of primary, revision, and endoscopic modified Lothrop procedure
      (EMLP) (Draf III) frontal sinus surgery and evaluate whether risk factors would
      help determine which patients would benefit from which procedures. METHODS: The
      study used a retrospective chart review. Endoscopic assessment of frontal ostium
      patency and patient reported symptoms were prospectively collected on patients
      who underwent frontal sinusotomy between January 2003 and December 2009. High
      risk cohorts were studied to assess their response to standard endoscopic sinus
      surgery (ESS) compared with EMLP. RESULTS: A total of 339 patients who met the
      inclusion and exclusion criteria underwent either primary or revision endoscopic
      frontal sinus surgery. The average +/- standard deviation (SD) length of follow
      up was 20.8 +/- 18.7 (95% confidence interval [CI], 18.0-22.9) months.
      Postsurgical recurrence of disease with persistence of symptoms requiring an EMLP
      occurred in 9 patients in the primary group and 38 in the revision group. The
      highest risk groups for failure of standard frontal sinusotomy were patients with
      nasal polyps, asthma, Lund-Mackay score >16, and frontal ostium size <4 mm
      (relative risk = 9.9, p < 0.0001). CONCLUSION: Patients with underlying asthma
      and polyposis as well as narrow frontal ostia and extensive radiological disease
      have a high failure rate from standard endoscopic frontal sinusotomy. In this
      patient group consideration should be given to offering the patient a primary
      EMLP procedure, which has excellent success rates with low risks and low
      morbidity.

PMID- 23135989
TI  - Synthesis of oxazolidinones by efficient fixation of atmospheric CO2 with
      propargylic amines by using a silver/1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)
      Dual-catalyst system.
AB  - This'll fix it: efficient fixation of atmospheric CO(2) has been achieved by the
      reaction of propargylic amines with a silver/DBU dual-catalyst system. Various
      oxazolidinones were synthesized in moderate to good yields by using substituted
      propargylic amines.

PMID- 23135990
TI  - Squaric acid mediated chemoselective PEGylation of proteins: reactivity of single
      step-activated alpha-amino poly(ethylene glycol)s.
AB  - The covalent attachment of poly(ethylene glycol) (PEG) to therapeutically active
      proteins (PEGylation) has become an important method to deal with the
      pharmacological difficulties of these polypeptides, such as short body-residence
      times and immunogenicity. However, the derivatives of PEG used for PEGylation
      lack further functional groups that would allow the addition of targeting or
      labeling moieties. Squaric acid diethyl ester was used for the chemoselective
      single-step activation of poly(ethylene glycol)s into the respective ester
      amides. The resultant selective protein-reactive poly(ethylene glycol)s were
      investigated with respect to their selectivity towards amino acid residues in
      bovine serum albumin (as a model protein). The presented procedure relies on a
      robust two-step protocol and was found to be selective towards lysine residues;
      the activated polyethers are efficient and stoichiometric PEGylation agents with
      a remarkable hydrolytic stability over a period of several days. By adjusting the
      pD value of the conjugation mixture, the chemoselectivity of the activated PEGs
      towards the alpha- and epsilon-amino groups of lysine methyl ester was
      effectively changed.

PMID- 23135992
TI  - Cardiac fibroblasts and cellular cross talk in heart failure.

PMID- 23135991
TI  - Endothelial dysfunction and cardiac allograft vasculopathy.
AB  - Cardiac allograft vasculopathy remains a major challenge to long-term survival
      after heart transplantation. Endothelial injury and dysfunction, as a result of
      multifactorial immunologic and nonimmunologic insults in the donor and the
      recipient, are prevalent early after transplant and may be precursors to overt
      cardiac allograft vasculopathy. Current strategies for managing cardiac allograft
      vasculopathy, however, rely on the identification and treatment of established
      disease. Improved understanding of mechanisms leading to endothelial dysfunction
      in heart transplant recipients may provide the foundation for the development of
      sensitive screening techniques and preventive therapies.

PMID- 23135993
TI  - 2D DIGE analysis of the bursa of Fabricius reveals characteristic proteome
      profiles for different stages of chicken B-cell development.
AB  - Antibody producing B-cells are an essential component of the immune system. In
      contrast to human and mice where B-cells develop in the bone marrow, chicken B
      cells develop in defined stages in the bursa of Fabricius, a gut associated
      lymphoid tissue. In order to gain a better understanding of critical biological
      processes like immigration of B-cell precursors into the bursa anlage, their
      differentiation and final emigration from the bursa we analyzed the proteome
      dynamics of this organ during embryonic and posthatch development. Samples were
      taken from four representative developmental stages (embryonic day (ED) 10, ED18,
      day 2, and day 28) and compared in an extensive 2D DIGE approach comprising six
      biological replicates per time point. Cluster analysis and PCA demonstrated high
      reliability and reproducibility of the obtained data set and revealed distinctive
      proteome profiles for the selected time points, which precisely reflect the
      differentiation processes. One hundred fifty three protein spots with
      significantly different intensities were identified by MS. We detected
      alterations in the abundance of several proteins assigned to retinoic acid
      metabolism (e.g. retinal-binding protein 5) and the actin-cytoskeleton (e.g.
      vinculin and gelsolin). By immunohistochemistry, desmin was identified as stromal
      cell protein associated with the maturation of B-cell follicles. Strongest
      protein expression difference (10.8-fold) was observed for chloride intracellular
      channel 2. This protein was thus far not associated with B-cell biology but our
      data suggest an important function in bursa B-cell development.

PMID- 23135994
TI  - Comparison of mRNA localization and regulation during endoplasmic reticulum
      stress in Drosophila cells.
AB  - Ire1 is an endoplasmic reticulum (ER) transmembrane protein that senses
      disturbances in protein folding homeostasis and contributes to a multifaceted
      response to stress. The nuclease activity of Ire1, in addition to splicing the
      mRNA encoding the transcription factor Xbp1, mediates mRNA degradation in
      response to ER stress through a pathway termed regulated Ire1-dependent decay
      (RIDD). We previously showed that ER targeting of substrates is necessary for
      RIDD; in this paper, we show that ER localization is also sufficient to induce
      decay in a normally unaffected mRNA. Using microarrays, we also measured relative
      mRNA degradation in the presence and absence of ER stress in Drosophila S2 cells,
      and determined mRNA membrane association using detergent fractionation. The vast
      majority of mRNAs that were strongly associated with the ER were degraded faster
      during ER stress in an Ire1-dependent manner, suggesting that RIDD is the default
      pathway for ER-localized mRNAs during stress. We also show that the mRNA encoding
      plexin A remains highly polysome associated during stress and escapes degradation
      by RIDD, and that its 5' untranslated region can protect a strong RIDD target
      from degradation. These results suggest that while translation is generally
      attenuated during ER stress, continued translation of certain messages can
      protect them from degradation by RIDD.

PMID- 23135995
TI  - Daydreamer, a Ras effector and GSK-3 substrate, is important for directional
      sensing and cell motility.
AB  - How independent signaling pathways are integrated to holistically control a
      biological process is not well understood. We have identified Daydreamer (DydA),
      a new member of the Mig10/RIAM/lamellipodin (MRL) family of adaptor proteins that
      localizes to the leading edge of the cell. DydA is a putative Ras effector that
      is required for cell polarization and directional movement during chemotaxis.
      dydA(-) cells exhibit elevated F-actin and assembled myosin II (MyoII), increased
      and extended phosphoinositide-3-kinase (PI3K) activity, and extended
      phosphorylation of the activation loop of PKB and PKBR1, suggesting that DydA is
      involved in the negative regulation of these pathways. DydA is phosphorylated by
      glycogen synthase kinase-3 (GSK-3), which is required for some, but not all, of
      DydA's functions, including the proper regulation of PKB and PKBR1 and MyoII
      assembly. gskA(-) cells exhibit very strong chemotactic phenotypes, as previously
      described, but exhibit an increased rate of random motility. gskA(-) cells have a
      reduced MyoII response and a reduced level of phosphatidylinositol (3,4,5)
      triphosphate production, but a highly extended recruitment of PI3K to the plasma
      membrane and highly extended kinetics of PKB and PKBR1 activation. Our results
      demonstrate that GSK-3 function is essential for chemotaxis, regulating multiple
      substrates, and that one of these effectors, DydA, plays a key function in the
      dynamic regulation of chemotaxis.

PMID- 23135996
TI  - Srv2/cyclase-associated protein forms hexameric shurikens that directly catalyze
      actin filament severing by cofilin.
AB  - Actin filament severing is critical for the dynamic turnover of cellular actin
      networks. Cofilin severs filaments, but additional factors may be required to
      increase severing efficiency in vivo. Srv2/cyclase-associated protein (CAP) is a
      widely expressed protein with a role in binding and recycling actin monomers
      ascribed to domains in its C-terminus (C-Srv2). In this paper, we report a new
      biochemical and cellular function for Srv2/CAP in directly catalyzing cofilin
      mediated severing of filaments. This function is mediated by its N-terminal half
      (N-Srv2), and is physically and genetically separable from C-Srv2 activities.
      Using dual-color total internal reflection fluorescence microscopy, we determined
      that N-Srv2 stimulates filament disassembly by increasing the frequency of
      cofilin-mediated severing without affecting cofilin binding to filaments.
      Structural analysis shows that N-Srv2 forms novel hexameric star-shaped
      structures, and disrupting oligomerization impairs N-Srv2 activities and in vivo
      function. Further, genetic analysis shows that the combined activities of N-Srv2
      and Aip1 are essential in vivo. These observations define a novel mechanism by
      which the combined activities of cofilin and Srv2/CAP lead to enhanced filament
      severing and support an emerging view that actin disassembly is controlled not by
      cofilin alone, but by a more complex set of factors working in concert.

PMID- 23135997
TI  - Decoupling nutrient signaling from growth rate causes aerobic glycolysis and
      deregulation of cell size and gene expression.
AB  - To survive and proliferate, cells need to coordinate their metabolism, gene
      expression, and cell division. To understand this coordination and the
      consequences of its failure, we uncoupled biomass synthesis from nutrient
      signaling by growing, in chemostats, yeast auxotrophs for histidine, lysine, or
      uracil in excess of natural nutrients (i.e., sources of carbon, nitrogen, sulfur,
      and phosphorus), such that their growth rates (GRs) were regulated by the
      availability of their auxotrophic requirements. The physiological and
      transcriptional responses to GR changes of these cultures differed markedly from
      the respective responses of prototrophs whose growth-rate is regulated by the
      availability of natural nutrients. The data for all auxotrophs at all GRs
      recapitulated the features of aerobic glycolysis, fermentation despite high
      oxygen levels in the growth media. In addition, we discovered wide bimodal
      distributions of cell sizes, indicating a decoupling between the cell division
      cycle (CDC) and biomass production. The aerobic glycolysis was reflected in a
      general signature of anaerobic growth, including substantial reduction in the
      expression levels of mitochondrial and tricarboxylic acid genes. We also found
      that the magnitude of the transcriptional growth-rate response (GRR) in the
      auxotrophs is only 40-50% of the magnitude in prototrophs. Furthermore, the
      auxotrophic cultures express autophagy genes at substantially lower levels, which
      likely contributes to their lower viability. Our observations suggest that a GR
      signal, which is a function of the abundance of essential natural nutrients,
      regulates fermentation/respiration, the GRR, and the CDC.

PMID- 23135998
TI  - MicroRNA-7-regulated TLR9 signaling-enhanced growth and metastatic potential of
      human lung cancer cells by altering the phosphoinositide-3-kinase, regulatory
      subunit 3/Akt pathway.
AB  - Recent evidence shows that microRNAs (miRNAs) contribute to the biological
      effects of Toll-like receptor (TLR) signaling on various cells. Our previous data
      showed that TLR9 signaling could enhance the growth and metastatic potential of
      human lung cancer cells. However, the potential role of miRNAs in the effects of
      TLR9 signaling on tumor biology remains unknown. In this paper, we first report
      that TLR9 signaling could reduce intrinsic miR-7 expression in human lung cancer
      cells. Furthermore, overexpression of miR-7 can significantly inhibit TLR9
      signaling-enhanced growth and metastatic potential of lung cancer cells in vitro
      and in vivo. Notably, we identify phosphoinositide-3-kinase, regulatory subunit 3
      (PIK3R3) as a novel target molecule of miR-7 in lung cancer cells by Western
      blotting and luciferase report assay. Further study shows that miR-7 inhibits the
      effects of TLR9 signaling on lung cancer cells through regulation of the
      PIK3R3/Akt pathway. These data suggest that miR-7 could act as a fine-tuner in
      regulating the biological effects of TLR9 signaling on human lung cancer cells,
      which might be helpful to the understanding of the potential role of miRNAs in
      TLR signaling effects on tumor biology.

PMID- 23135999
TI  - Fingerloop activates cargo delivery and unloading during cotranslational protein
      targeting.
AB  - During cotranslational protein targeting by the signal recognition particle
      (SRP), information about signal sequence binding in the SRP's M domain must be
      effectively communicated to its GTPase domain to turn on its interaction with the
      SRP receptor (SR) and thus deliver the cargo proteins to the membrane. A
      universally conserved "fingerloop" lines the signal sequence-binding groove of
      SRP; the precise role of this fingerloop in protein targeting has remained
      elusive. In this study, we show that the fingerloop plays important roles in SRP
      function by helping to induce the SRP into a more active conformation that
      facilitates multiple steps in the pathway, including efficient recruitment of SR,
      GTPase activation in the SRP*SR complex, and most significantly, the unloading of
      cargo onto the target membrane. On the basis of these results and recent
      structural work, we propose that the fingerloop is the first structural element
      to detect signal sequence binding; this information is relayed to the linker
      connecting the SRP's M and G domains and thus activates the SRP and SR for
      carrying out downstream steps in the pathway.

PMID- 23136000
TI  - Urine concentration in the diabetic mouse requires both urea and water
      transporters.
AB  - The regulation of the inner medullary collecting duct (IMCD) urea transporters
      (UT-A1, UT-A3) and aquaporin-2 (AQP2) and their interactions in diabetic animals
      is unknown. We investigated whether the urine concentrating defect in diabetic
      animals was a function of AQP2, the UT-As, or both transporters. UT-A1/UT-A3
      knockout (UT-A1/A3 KO) mice produce dilute urine. We gave wild-type (WT) and UT
      A1/A3 KO mice vasopressin via minipump for 7 days. In WT mice, vasopressin
      increased urine osmolality from 3,000 to 4,550 mosmol/kgH(2)O. In contrast, urine
      osmolality was low (800 mosmol/kgH(2)O) in the UT-A1/A3 KOs and remained low
      following vasopressin. Surprisingly, AQP2 protein abundance increased in UT-A1/A3
      KO (114%) and WT (92%) mice. To define the role of UT-A1 and UT-A3 in the
      diabetic responses, WT and UT-A1/A3 KO mice were injected with streptozotocin
      (STZ). UT-A1/A3 KO mice showed only 40% survival at 7 days post-STZ injection
      compared with 70% in WT. AQP2 did not increase in the diabetic UT-A1/A3 KO mice
      compared with a 133% increase in WT diabetic mice. Biotinylation studies in rat
      IMCDs showed that membrane accumulation of UT-A1 increased by 68% in response to
      vasopressin in control rats but was unchanged by vasopressin in diabetic rat
      IMCDs. We conclude that, even with increased AQP2, UT-A1/UT-A3 is essential to
      optimal urine concentration. Furthermore, UT-A1 may be maximally membrane
      associated in diabetic rat inner medulla, making additional stimulation by
      vasopressin ineffective.

PMID- 23136001
TI  - Vasopressin inhibits apoptosis in renal collecting duct cells.
AB  - The peptide hormone arginine vasopressin (AVP) plays a critical role in
      regulating salt and water transport in the mammalian kidney. Recent studies have
      also demonstrated that AVP can promote cell survival in neuronal cells through V1
      receptors. The current study addresses whether AVP can inhibit apoptosis in
      kidney collecting duct cells via V2 receptors and also explores the downstream
      signaling pathways regulating this phenomenon. Terminal deoxynucleotidyl
      transferase-mediated dUTP-biotin nick-end labeling analysis and caspase cleavage
      assays demonstrated that 1-desamino-8-d-arginine vasopressin (dDAVP) inhibited
      apoptosis induced by various agents (staurosporine, actinomycin D, and
      cycloheximide) in cultured mouse cortical collecting duct cells (mpkCCD).
      Incubation with dDAVP also inhibited apoptosis induced by the
      phosphatidylinositol 3-kinase (PI3K) pathway inhibitor LY294002, suggesting that
      the antiapoptotic effects of dDAVP are largely independent of PI3K signaling. The
      V2 receptor antagonist SR121463 completely abolished the antiapoptotic effects of
      dDAVP. In addition, incubation with 8-cpt-cAMP, a cell-permeable analog of cAMP,
      reproduced the antiapoptotic effects of dDAVP. Both dDAVP and 8-cpt-cAMP
      increased phosphorylation of proapoptotic Bcl-2 family members Bad and Bok. Bad
      phosphorylation at Ser-112 and Ser-155 is known to inhibit its proapoptotic
      activity. Preincubation with H89 blocked dDAVP-induced phosphorylation of both
      Bad and Bok, suggesting dependence on protein kinase A (PKA). This study provides
      evidence that AVP can inhibit apoptosis through the V2 receptor and downstream
      cAMP-mediated pathways in mammalian kidney. The antiapoptotic action of AVP may
      be relevant to a number of physiological and pathophysiological conditions
      including osmotic tolerance in the inner medulla, escape from AVP-induced
      antidiuresis, and polycystic kidney disease.

PMID- 23136002
TI  - Temporal delays and individual variation in antidiuretic response to
      desmopressin.
AB  - This study aimed to estimate the relationship between pharmacokinetics and the
      antidiuretic effect of desmopressin. In the investigator-blind, randomized,
      parallel group study, 5 dose groups and 1 placebo group, each consisting of 12
      healthy, overhydrated, nonsmoking male subjects 18-55 yr of age were infused
      intravenously over 2 h with placebo or 30, 60, 125, 250, and 500 ng desmopressin
      in 50 ml of normal saline. Plasma desmopressin and urine osmolality rose by
      variable amounts during the infusions of 60, 125, 250, and 500 ng desmopressin.
      Plotting mean urine osmolality against the concurrent mean plasma desmopressin
      yielded a temporal delay between pharmacokinetic (PK) and -dynamic (PD) responses
      in all dose groups. Using simulation from the indirect-response model, assuming a
      constant (4 ng/ml) desmopressin concentration, this delay between PK and PD was
      estimated at 4 h (10th-90th percentile: 1.8-8.1). Within each group, however,
      there were large individual variations (2- to 10-fold) in the magnitude and
      duration of the antidiuretic effect. The antidiuretic effect of intravenous
      desmopressin in water-loaded healthy adults varies considerably due largely to
      factors other than individual differences in pharmacokinetics. The antidiuretic
      effect is time as well as dose dependent and may be self-amplifying. The most
      likely explanation for these findings is that the time required for a given level
      of plasma desmopressin to exert its maximum antidiuretic effect varies markedly
      from person to person due to individual differences in the kinetics of one or
      more of the intracellular mechanisms that promote the reabsorption of solute-free
      water by principal cells in renal collecting tubules.

PMID- 23136003
TI  - Response of the mitochondrial proteome of rat renal proximal convoluted tubules
      to chronic metabolic acidosis.
AB  - Metabolic acidosis is a common clinical condition that is caused by a decrease in
      blood pH and bicarbonate concentration. Increased extraction and mitochondrial
      catabolism of plasma glutamine within the renal proximal convoluted tubule
      generates ammonium and bicarbonate ions that facilitate the excretion of acid and
      partially restore acid-base balance. Previous studies identified only a few
      mitochondrial proteins, including two key enzymes of glutamine metabolism, which
      are increased during chronic acidosis. A workflow was developed to characterize
      the mitochondrial proteome of the proximal convoluted tubule. Based upon the
      increase in specific activity of cytochrome c oxidase, the isolated mitochondria
      were enriched eightfold. Two-dimensional liquid chromatography coupled with mass
      spectrometry was utilized to compare mitochondrial-enriched samples from control
      and chronic acidotic rats. Proteomic analysis identified 901 proteins in the
      control and acidotic samples. Further analysis identified 37 peptides that
      contain an N-epsilon-acetyl-lysine; of these, 22 are novel sites. Spectral
      counting analysis revealed 33 proteins that are significantly altered in
      abundance in response to chronic metabolic acidosis. Western blot analysis was
      performed to validate the calculated changes in abundance. Thus the current study
      represents the first comprehensive analysis of the mitochondrial proteome of the
      rat renal proximal convoluted tubule and its response to metabolic acidosis.

PMID- 23136004
TI  - Analogs of bardoxolone methyl worsen diabetic nephropathy in rats with additional
      adverse effects.
AB  - Bardoxolone methyl is an antioxidant inflammation modulator acting through
      induction of Keap1-Nrf2 pathway. Results from a recent phase IIb clinical trial
      reported that bardoxolone methyl was associated with improvement in the estimated
      glomerular filtration rate in patients with advanced chronic kidney disease and
      Type 2 diabetes. However, increases in albuminuria, serum transaminase, and
      frequency of adverse events were noted. We studied the effect of 3-mo treatment
      with RTA 405, a synthetic triterpenoid analog of bardoxolone methyl in Zucker
      diabetic fatty rats with overt Type 2 diabetes. Rats were treated from 3 mo of
      age with vehicle, RTA 405, ramipril, or RTA 405 plus ramipril. RTA 405 caused
      severe changes in food intake and diuresis with decline in body weight, worsening
      of dyslipidemia, and increase in blood pressure. Early elevation in serum
      transaminase was followed by liver injury. RTA 405 worsened proteinuria,
      glomerulosclerosis, and tubular damage. Ramipril was renoprotective, but when
      given with RTA 405 it was not able to limit its worsening effects. These data
      could be due to degradation products in the drug substance used, as disclosed by
      the company once the study was concluded. To overcome such a drawback, the
      company offered to test dh404, a variant of RTA 405, in Zucker diabetic fatty
      rats. The dh404 did not display beneficial effects on proteinuria,
      glomerulosclerosis, and interstitial inflammation. Rather, kidneys from three
      rats receiving dh404 showed the presence of a granulomatous and inflammatory
      process reminiscent of a pseudotumor. Altogether these data raise serious
      concerns on the use of bardoxolone analogs in Type 2 diabetic nephropathy.

PMID- 23136005
TI  - Increased renal sympathetic nerve activity leads to hypertension and renal
      dysfunction in offspring from diabetic mothers.
AB  - The exposure of the fetus to a hyperglycemic environment promotes the development
      of hypertension and renal dysfunction in the offspring at adult age. We evaluated
      the role of renal nerves in the hypertension and renal changes seen in offspring
      of diabetic rats. Diabetes was induced in female Wistar rats (streptozotocin, 60
      mg/kg ip) before mating. Male offspring from control and diabetic dams were
      studied at an age of 3 mo. Systolic blood pressure measured by tail cuff was
      increased in offspring of diabetic dams (146 +/- 1.6 mmHg, n = 19, compared with
      117 +/- 1.4 mmHg, n = 18, in controls). Renal function, baseline renal
      sympathetic nerve activity (rSNA), and arterial baroreceptor control of rSNA were
      analyzed in anesthetized animals. Glomerular filtration rate, fractional sodium
      excretion, and urine flow were significantly reduced in offspring of diabetic
      dams. Two weeks after renal denervation, blood pressure and renal function in
      offspring from diabetic dams were similar to control, suggesting that renal
      nerves contribute to sodium retention in offspring from diabetic dams. Moreover,
      basal rSNA was increased in offspring from diabetic dams, and baroreceptor
      control of rSNA was impaired, with blunted responses to infusion of nitroprusside
      and phenylephrine. Thus, data from this study indicate that in offspring from
      diabetic mothers, renal nerves have a clear role in the etiology of hypertension;
      however, other factors may also contribute to this condition.

PMID- 23136007
TI  - The effect of an active guest on the spin crossover phenomenon.

PMID- 23136006
TI  - Gain-of-function variant of the human epithelial sodium channel.
AB  - Epithelial Na(+) channel (ENaC) mutations are associated with several human
      disorders, underscoring the importance of these channels in human health. Recent
      human genome sequencing projects have revealed a large number of ENaC gene
      variations, several of which have been found in individuals with salt-sensitive
      hypertension, cystic fibrosis, and other disorders. However, the functional
      consequences of most variants are unknown. In this study, we used the Xenopus
      oocyte expression system to examine the functional properties of a human ENaC
      variant. Oocytes expressing alphabetagammaL511Q human ENaCs showed 4.6-fold
      greater amiloride-sensitive currents than cells expressing wild-type channels.
      The gammaL511Q variant did not significantly alter channel surface expression.
      Single channel recordings revealed that the variant had fourfold higher open
      probability than wild type. In addition, gammaL511Q largely eliminated the Na(+)
      self-inhibition response, which reflects a downregulation of ENaC open
      probability by extracellular Na(+). Moreover, gammaL511Q diminished chymotrypsin
      induced activation of the mutant channel. We conclude that gammaL511Q is a gain
      of-function human ENaC variant. Our results suggest that gammaL511Q enhances ENaC
      activity by increasing channel open probability and dampens channel regulation by
      extracellular Na(+) and proteases.

PMID- 23136009
TI  - Boronium-cation-based ionic liquids as hypergolic fluids.
AB  - Two series of boronium-cation-based ionic liquids were prepared and fully
      characterized by (1)H, (13)C, and (11)B NMR and infrared spectroscopy,
      differential scanning calorimetry (DSC), and elemental analysis. The structure of
      bis(1-methyl-1H-imidazole-3-yl)dihydroboronium dicyanoborohydride (5 a) was
      determined by single-crystal X-ray diffraction. The densities of these ionic
      liquids range from 1.05 to 1.28 g cm(-3), and the heats of formation, predicted
      on the basis of Gaussian 03 calculations, fall between -164.6 and 430.5 kJ mol(
      1). Compound 5 b, bis(1-allyl-1H-imidazole-3-yl)dihydroboronium
      dicyanoborohydride, exhibits the lowest viscosity (35 mPa s) and shortest
      ignition-delay time (14 ms) in combination with 100 % HNO(3).

PMID- 23136008
TI  - Enhanced survival of wild-type and Lurcher Purkinje cells in vitro following
      inhibition of conventional PKCs or stress-activated MAP kinase pathways.
AB  - Recent studies using both dissociated and organotypic cell cultures have shown
      that heterozygous Lurcher (Lc/+) Purkinje cells (PCs) grown in vitro share many
      of the same survival and morphological characteristics as Lc/+ PCs in vivo. We
      have used this established tissue culture system as a valuable model for studying
      cell death mechanisms in a relatively simple system where neurodegeneration is
      induced by a constitutive cation leak mediated by the Lurcher mutation in the
      delta2 glutamate receptor (GluRdelta2). In this study, Ca(++) imaging and
      immunocytochemistry studies indicate that intracellular levels of Ca(++) are
      chronically increased in Lc/+ PCs and the concentration and/or distribution of
      the conventional PKCgamma isoform is altered in degenerating Lc/+ PCs. To begin
      to characterize the molecular mechanisms that regulate Lc/+ PC death, the
      contributions of conventional PKC pathways and of two MAP kinase family members,
      JNK and p38, were examined in slice cultures from wild-type and Lc/+ mutant mouse
      cerebellum. Cerebellar slice cultures from P0 pups were treated with either a
      conventional PKC inhibitor, a JNK inhibitor, or a p38 inhibitor either from 0 to
      14 or 7 to 14 DIV. Treatment with either of the three inhibitors from 0 DIV
      significantly increased wild type and Lc/+ PC survival through 14 DIV, but only
      Lc/+ PC survival was significantly increased following treatments from 7 to 14
      DIV. The results suggest that multiple PC death pathways are induced by the
      physical trauma of making organotypic slice cultures, naturally-occurring
      postnatal cell death, and the GluRdelta2 (Lc) mutation.

PMID- 23136010
TI  - Physical activity behaviour in patients with metabolic syndrome.
AB  - STUDY/PRINCIPLES: Physical activity improves the clinical course of the metabolic
      syndrome and its risk factors. The aim of this study was to investigate the
      physical activity behaviour in patients with metabolic syndrome in regard to the
      recommendation of the Federal Offices of Public Health (BAG) and Sports (BASPO):
      "to exercise half an hour a day  at a medium intensity." METHODS: 47 patients
      with metabolic syndrome were recruited from the Outpatient Department of the
      Division of Internal Medicine of the University Hospital Zurich. 24 patients were
      included and physical activity behaviour was assessed by using the International
      Physical Activity Questionnaires. RESULTS: All of the patients knew about the
      positive effect of physical activity on the course of the metabolic syndrome
      although 62% of the patients (n = 15) had no knowledge of the BAG/BASPO
      recommendations. 54% of the patients (n = 13) performed physical activity in
      accordance to the recommendation with or without knowing the recommendations.
      Most of the patients (n = 21, 87%) were motivated to improve their physical
      activity, but missing opportunities and instructions were important reasons for
      not being physically active. CONCLUSION: Patients with metabolic syndrome usually
      know about the positive effect of physical activity on the course of their
      disorder and are motivated to improve physical activity behaviour. However, the
      BAG/BASPO recommendations are not widely known and should therefore become more
      popular and better communicated particularly to patients with metabolic syndrome.
      Furthermore, patients have to be supported and instructed practically how to get
      physically active in accordance with their co-morbidities.

PMID- 23136011
TI  - Gut microbiota regulates NKG2D ligand expression on intestinal epithelial cells.
AB  - Intestinal epithelial cells (IECs) are one of a few cell types in the body with
      constitutive surface expression of natural killer group 2 member D (NKG2D)
      ligands, although the magnitude of ligand expression by IECs varies. Here, we
      investigated whether the gut microbiota regulates the NKG2D ligand expression on
      small IECs. Germ-free and ampicillin-treated mice were shown to have a
      significant increase in NKG2D ligand expression. Interestingly, vancomycin
      treatment, which propagated the bacterium Akkermansia muciniphila and reduced the
      level of IFN-gamma and IL-15 in the intestine, decreased the NKG2D ligand
      expression on IECs. In addition, a similar increase in A. muciniphila and a
      decreased NKG2D ligand expression was seen after feeding with dietary
      xylooligosaccharides. A pronounced increase in NKG2D ligand expression was
      furthermore observed in IL-10-deficient mice. In summary, our results suggest
      that the constitutive levels of NKG2D ligand expression on IECs are regulated by
      microbial signaling in the gut and further disfavor the intuitive notion that IEC
      NKG2D ligand expression is caused by low-grade immune reaction against commensal
      bacteria. It is more likely that constitutively high IEC NKG2D ligand expression
      is kept in check by an intestinal regulatory immune milieu induced by members of
      the gut microbiota, for example A. muciniphila.

PMID- 23136012
TI  - Fully covered self-expanding metal stents for benign colonic strictures.
AB  - BACKGROUND AND STUDY AIMS: Uncovered self-expanding metal stents offer effective
      relief for colonic obstruction. The aim of this study was to determine the
      effectiveness of fully covered self-expanding metal stents (FCSEMSs) in the
      treatment of benign colonic strictures. PATIENTS AND METHODS: All patients
      presenting with a symptomatic benign colonic stricture (occlusion or
      subocclusion) during a 6-year study period were treated with FCSEMSs. The stents
      were placed and removed 4 - 6 weeks later at one of 10 endoscopy centers. The
      efficacy of the stent (clinical and radiological signs of colonic decompression
      within 48 hours), technical success, stent retrieval, safety, and recurrence of
      symptoms were evaluated during follow-up. Univariate and multivariate analyses
      were performed to identify variables associated with clinical success, stent
      migration, and symptom recurrence. RESULTS: The study included 43 patients (24
      men, 19 women; mean age 67.6 +/- 10.4) with occlusive (n = 18) or subocclusive
      symptoms (n = 25) due to anastomotic (n = 40), post-ischemic (n = 2), or post
      radiation (n = 1) strictures. Insertion was successful in all patients. Clinical
      success was obtained in 35 patients (81 %). Migration was observed in 27 patients
      (63 %). The median duration of stenting was 21 days (95 %CI 17.8 - 35.4 days).
      Multivariate analysis showed that stents more than 20 mm wide migrated
      significantly less often. Recurrence of obstructive symptoms was observed in 23
      patients (53 %), irrespective of migration. No predictive factors for recurrence
      or clinical efficacy were found. CONCLUSIONS: FCSEMSs for treatment of
      symptomatic benign colonic strictures are safe and effective, despite a high rate
      of spontaneous migration.

PMID- 23136013
TI  - Is nasal packing necessary after septoplasty? A meta-analysis.
AB  - BACKGROUND: Nasal packing is routinely used after septoplasty because it is
      believed to decrease risk of postoperative bleeding, hematomas, and adhesions.
      Multiple studies have shown, however, that there are numerous complications
      associated with nasal packing. The purpose of this work was to perform a meta
      analysis on the existing literature to evaluate the role of nasal packing after
      septoplasty. METHODS: Two independent reviewers conducted a literature search
      using EMBASE, OVID, Medline, PubMed, Google scholar, Cochrane Library, and
      reference list review from 1966 to August 2010 to identify studies assessing
      nasal packing after septoplasty. All papers were reviewed for study design,
      results, and were assigned an Oxford level of evidence grade, Detsky score, and
      Methodological Index for Nonrandomized Studies (MINORS) score. RESULTS: Sixteen
      papers were identified that met the inclusion criteria. Eleven papers were
      randomized control trials, 3 were prospective, and 2 were retrospective studies.
      Nasal packing did not show benefit in reducing postoperative bleeding, hematomas,
      septal perforations, adhesions, or residual deviated nasal septum. There was,
      however, an increase in postoperative infections. Two studies using fibrin
      products as nasal packing showed a decreased bleeding rate. CONCLUSION: Nasal
      packing after septoplasty does not show any postoperative benefits. Fibrin
      products show a possibility of decreasing postoperative bleeding. Routine use of
      nasal packing after septoplasty is not warranted. This is the first meta-analysis
      conducted on this topic.

PMID- 23136014
TI  - Two-photon fluorescent imaging of myelination in the spinal cord.
AB  - Myelination is a fundamental biological process in the vertebrate nervous system.
      Damage to or malformation of myelin can lead to various neurological diseases;
      for example, demyelination in the spinal cord is a major cause of paralysis of
      patients suffering from multiple sclerosis and related diseases. The ability to
      directly track myelin levels in the spinal cord is needed in order to assess the
      efficacy of therapeutics in promoting myelin repair. To address this unmet need,
      4-((E)-4-((E)-4-aminostyryl)-2,5-dimethoxystyryl)-N-methylaniline, known as Case
      Imaging Compound (CIC), has been developed as a myelin-targeted fluorescent
      imaging agent that selectively binds to myelin. CIC was synthesized via an
      improved route and evaluated as a fluorescent probe for two-photon fluorescent
      imaging of myelin in the spinal cord in both demyelinated and dysmyelinated
      models. In vitro and ex vivo tissue staining both suggest that CIC selectively
      binds to in animal models. Further evaluation in animal models indicated that CIC
      is sensitive to differences in myelin content in healthy versus pathological
      myelin. CIC could potentially be useful in the development and evaluation of
      novel therapies for multiple sclerosis and other demyelinating diseases.

PMID- 23136015
TI  - Pressure baseline correction and high-precision CO2 clumped-isotope (?47)
      measurements in bellows and micro-volume modes.
AB  - RATIONALE: CO(2) 'clumped-isotope' measurements (tracking enrichment of
      (16)O(13)C(18)O, reported as ?(47) values, on CO(2) derived from carbonate
      minerals or the atmosphere) are becoming central to a wide range of geochemical
      investigations. We present a novel approach to address problems with instrument
      stability, external precision, and the analysis of small samples that have
      hampered the advancement of Delta(47) measurements. METHODS: We measured
      Delta(47) values on CO(2) gases introduced via dual inlet to an isotope ratio
      mass spectrometer. We developed a method for determining the 'pressure baseline'
      and integrating a correction to ion beam intensity measurements during analysis.
      We then tested this approach for both bellows and micro-volume modes of sample
      introduction. Heated gas and equilibrated gas lines (Delta(47) vs. delta(47))
      established the effectiveness of this correction. RESULTS: We have determined
      that drift in instrument calibration that compromises Delta(47) measurements
      results from a shift in the baseline signal on sensitive collectors (m/z 47, 48,
      and 49) that occurs when gas is admitted to the ion source. Applying a 'pressure
      baseline' (PBL) correction significantly stabilizes ?(47) measurements and
      reduces the dependence of ?(47) values on delta(47) values by up to an order of
      magnitude. CONCLUSIONS: PBL-corrected heated gas and equilibrated gas
      calibrations in bellows and micro-volume modes are nearly identical and stable
      through time. Introduction of the PBL correction, a revision to the absolute
      reference frame approach to determining Delta(47) values, dramatically improves
      the external precision of Delta(47) measurements to near instrumental analytical
      uncertainty (6-8 ppm (1sigma) in bellows mode; 10-12 ppm in micro-volume mode).

PMID- 23136016
TI  - Laser diode thermal desorption mass spectrometry for the analysis of quinolone
      antibiotic residues in aquacultured seafood.
AB  - RATIONALE: Veterinary drug residue analysis of meat and seafood products is an
      important part of national regulatory agency food safety programs to ensure that
      consumers are not exposed to potentially dangerous substances. Complex tissue
      matrices often require lengthy extraction and analysis procedures to identify
      improper animal drug treatment. Direct and rapid analysis mass spectrometry
      techniques have the potential to increase regulatory sample analysis speed by
      eliminating liquid chromatographic separation. METHODS: Flumequine, oxolinic
      acid, and nalidixic acid were extracted from catfish, shrimp, and salmon using
      acidified acetonitrile. Extracts were concentrated, dried onto metal sample
      wells, then rapidly desorbed (6 s) with an infrared diode laser for analysis by
      laser diode thermal desorption atmospheric pressure chemical ionization with
      tandem mass spectrometry (LDTD-MS/MS). Analysis was conducted in selected
      reaction monitoring mode using piromidic acid as internal standard. RESULTS: Six
      point calibration curves for each compound in extracted matrix were linear with
      r(2) correlation greater than 0.99. The method was validated by analyzing 23
      negative samples and 116 fortified samples at concentrations of 10, 20, 50, 100,
      and 600 ng/g. Average recoveries of fortified samples were greater than 77% with
      method detection levels ranging from 2 to 7 /g. Three product ion transitions
      were acquired per analyte to identify each residue. CONCLUSIONS: A rapid method
      for quinolone analysis in fish muscle was developed using LDTD-MS/MS. The total
      analysis time was less than 30 s per sample; quinolone residues were detected
      below 10 ng/g and in most cases residue identity was confirmed. This represents
      the first application of LDTD to tissue extract analysis. Published 2012. This
      article is a US Government work and is in the public domain in the USA.

PMID- 23136017
TI  - Probing the dynamic reversibility and generation of dynamic combinatorial
      libraries in the presence of bacterial model oligopeptides as templating guests
      of tetra-carbohydrazide macrocycles using electrospray mass spectrometry.
AB  - RATIONALE: Over the past few decades, bacterial resistance to antibiotics has
      emerged as a real threat to human health. Accordingly, there is an urgent demand
      for the development of innovative strategies for discovering new antibiotics. We
      present the first use of tetra-carbohydrazide cyclophane macrocycles in dynamic
      combinatorial chemistry (DCC) and molecular recognition as chiral hosts binding
      oligopeptides, which mimic bacterial cell wall. This study introduces an
      innovative application of electrospray ionisation time-of-flight mass
      spectrometry (ESI-TOF MS) to oligopeptides recognition using DCC. METHODS: A
      small dynamic library composed of eight functionalised macrocycles has been
      generated in solution and all members were characterised by ESI-TOF MS. We also
      probed the dynamic reversibility and mechanism of formation of tetra
      carbohydrazide cyclophanes in real-time using ESI-TOF MS. RESULTS: Dynamic
      reversibility of tetra-carbohydrazide cyclophanes is favored under thermodynamic
      control. The mechanism of formation of tetra-carbohydrazide cyclophanes involves
      key dialdehyde intermediates, which have been detected and assigned according to
      their high-resolution m/z values. Three members of the dynamic library bind
      efficiently in the gas phase to a selection of oligopeptides, unique to bacteria,
      allowing observation of host/guest complex ions in the gas phase. CONCLUSIONS: We
      probed the mechanism of the [2+2]-cyclocondensation reaction forming library
      members, proved dynamic reversibility of tetra-carbohydrazide cyclophanes and
      showed that complex ions formed between library members and hosts can be observed
      in the gas phase, allowing the solution of an important problem of biological
      interest.

PMID- 23136018
TI  - Confident identification of isomeric N-glycan structures by combined ion mobility
      mass spectrometry and hydrophilic interaction liquid chromatography.
AB  - RATIONALE: A central issue in glycan mass analysis is the ambiguity of structural
      assignments due to the heterogeneity and complexity of glycan structures. Ion
      mobility mass spectrometry (IM-MS) has the potential to separate isomeric glycans
      depending on their unique collisional cross section especially when coupled with
      hydrophilic interaction liquid chromatography (HILIC). METHODS: Ten
      pyridylaminated biantennary N-glycans including isomeric structures were measured
      by electrospray ionization quadrupole-time-of-flight mass spectrometry with an
      ion mobility phase. We investigated which adduct ions would be suitable for good
      separation in the ion mobility phase. The differences in observed drift time of
      isomeric glycans were assessed by molecular dynamics (MD) simulations in vacuum.
      Connecting an HILIC system with IM-MS provided another, augmented separation
      mode. RESULTS: By selecting doubly protonated precursor ion species, we succeeded
      in separating a pair of isomeric glycans in the ion mobility phase with
      reasonable resolution. MD simulations of monogalactosylated glycan isomers
      indicate that the galactosylated Man alpha1-3 branch preferentially folds back to
      the core chitobiose portion to form a compact structure. IM-MS combined with
      HILIC resulted in even clearer separation of isomeric glycans within 15 min.
      CONCLUSIONS: A combination of IM-MS with an HILIC system is eminently suitable
      for the confident and rapid distinction of glycan structures within a defined
      mixture.

PMID- 23136019
TI  - Metal cation detection in positive ion mode electrospray ionization mass
      spectrometry using a tetracationic salt as a gas-phase ion-pairing agent:
      evaluation of the effect of chelating agents on detection sensitivity.
AB  - RATIONALE: The detection of metal cations continues to be essential in many
      scientific and industrial areas of interest. The most common electrospray
      ionization mass spectrometry (ESI-MS) approach involves chelating the metal ions
      and detecting the organometallic complex in the negative ion mode. However, it is
      well known that negative ion mode ESI-MS is generally less sensitive than the
      positive ion mode. To achieve greater sensitivity, it is necessary to examine the
      feasibility of detecting the chelated metal cations in positive ion mode ESI-MS.
      METHODS: Since highly solvated native metal cations have relatively low
      ionization efficiency in ESI-MS, and can be difficult to detect in the positive
      ion mode, a tetracationic ion-pairing agent was added to form a complex with the
      negatively charged metal chelate. The use of the ion-pairing agent leads to the
      generation of an overall positively charged complex, which can be detected at
      higher m/z values in the positive ion mode by electrospray ionization linear
      quadrupole ion trap mass spectrometry. RESULTS: Thirteen chelating agents with
      diverse structures were evaluated in this study. The nature of the chelating
      agent played as important a role as was previously determined for cationic
      pairing agents. The detection limits of six metal cations reached sub-picogram
      levels and significant improvements were observed when compared to negative ion
      mode detection where the metal-chelates were monitored without adding the ion
      pairing reagent (IPR). Also, selective reaction monitoring (SRM) analyses were
      performed on the ternary complexes, which improved detection limits by one to
      three orders of magnitude. CONCLUSIONS: With this method it was possible to
      analyze the metal cations in the positive ion mode ESI-MS with the advantage of
      speed, sensitivity and selectivity. The optimum solution pH for this type of
      analysis is 5-7. Tandem mass spectrometry (MS/MS) further increases the
      sensitivity. Speciation is straightforward making this a broadly useful approach
      for the analysis of metal ions.

PMID- 23136020
TI  - Differentiation of isomeric pentose disaccharides by electrospray ionization
      tandem mass spectrometry and discriminant analysis.
AB  - RATIONALE: The structural characterization of unknown oligosaccharides remains a
      big challenge since a large number of isomeric structures are possible even for
      disaccharides. In this work, electrospray ionization collision-induced
      dissociation tandem mass spectrometry (ESI-CID-MS/MS) was used for the
      differentiation of isomeric pentose disaccharides, alpha-(1 -> 5)-L-arabinobiose
      (Ara(2)) and beta-(1 -> 4)-D-xylobiose (Xyl(2)). METHODS: ESI-MS/MS spectra of [M
      + Li](+) and [M + Na](+) ions of Ara(2) and Xyl(2), as well as these precursor
      ions of (18)O-labelled disaccharides, were acquired using two mass spectrometers
      equipped with different analyzers: LIT (linear ion trap) and Q-TOF (quadrupole
      time-of-flight). RESULTS: Product ions observed in MS/MS spectra arise from the
      cleavage at the nonreducing side of the glycosidic bond (Y(1)(+)) and from cross
      ring cleavages (0,1)A(2)(+), (0,2)A(2)(+), and (0,3)A(2)(+) at the reducing
      residue. Statistically significant differences were observed between the relative
      abundance of specific product ions, when comparing both disaccharides. These
      differences allowed discriminant models to be built and to propose a criterion
      using the relative abundances of selected ions capable of discriminating between
      the isomers for both adduct ions and spectrometers. CONCLUSIONS: Isomeric pentose
      disaccharides can be distinguished based on the fragmentation of both [M + Li](+)
      and [M + Na](+) ions and using different mass spectrometers. However, LIT
      instrument has a better discriminant power.

PMID- 23136021
TI  - Simulated gastrointestinal digestion of Pru ar 3 apricot allergen: assessment of
      allergen resistance and characterization of the peptides by ultra-performance
      liquid chromatography/electrospray ionisation mass spectrometry.
AB  - RATIONALE: Non-specific lipid transfer proteins (ns-LTPs) are major food
      allergens of the Rosaceae family. The severity of allergic reactions often
      relates to resistance of the allergen to digestion. Thus, it is important to
      evaluate the digestibility of these proteins and characterise the peptides
      generated in the gastrointestinal tract. METHODS: Simulated gastrointestinal
      digestion of purified allergen Pru ar 3 was performed using pepsin for the
      gastric phase in aqueous HCl at pH = 2 and chymotrypsin and trypsin for the
      intestinal phase in aqueous NH(4)HCO(3) at pH = 7.8. The peptide mixture obtained
      was analysed by ultra-performance liquid chromatography/electrospray ionisation
      mass spectrometry (UPLC/ESI-MS). Peptide sequences were identified by comparing
      their molecular mass to that obtained by in silico digestion, and were confirmed
      by the ions obtained by in-source fragmentation. Semi-quantification was
      performed for the intact protein by comparison with internal standards. RESULTS:
      The resistance to gastrointestinal digestion of Pru ar 3 allergen was evaluated
      to be 9%. This value is consistent with that found for grape LTP, but much lower
      than the resistance found for peach LTP (35%). All the peptides generated were
      identified by ESI-MS on the basis of their molecular mass and from the ions
      generated from in-source fragmentation. Apart from low molecular mass peptides,
      five high molecular mass peptides (4500-7000 Da) containing disulphide bridges
      were identified. ESI-MS of the intact protein indicated a less compact folded
      structure when compared to that of the homologous peach LTP. CONCLUSIONS: An
      extensive characterisation of the peptides generated from the gastrointestinal
      digestion of Pru ar 3 allergen was performed here for the first time via UPLC/ESI
      MS analysis. The digestibility of the allergen was evaluated and compared with
      that of other LTPs, demonstrating that only a small amount of undigested protein
      remains, and that specific proteolytic action involves immunodominant epitopes.
      These data might explain the lower allergenicity of apricot LTP compared to peach
      LTP, despite their high sequence homology.

PMID- 23136022
TI  - Identification of xanthones from Swertia punicea using high-performance liquid
      chromatography coupled with electrospray ionization tandem mass spectrometry.
AB  - RATIONALE: Swertia punicea Hemsl. (Gentianaceae) are used mainly for the
      treatment of acute bilious hepatitis, cholecystitis, fever, intoxification and
      jaundice in China, as a traditional Chinese folk medicine. Xanthones as the main
      chemical components of Swertia punicea have many possible pharmacological
      properties, such as hepatoprotective and anti-HIV. In order to obtain an overall
      picture of the xanthones of Swertia punicea, high-performance liquid
      chromatography diode-array detection/tandem mass spectrometry (HPLC/DAD-ESI
      MS(n)) was applied to the structural characterization of xanthones in ethyl
      acetate and acetone extracts. METHODS: The ESI-MS fragmentation behaviors of
      xanthones were investigated based on the 17 reference xanthones and then applied
      to the structural characterization of xanthones in ethyl acetate and acetone
      extracts of Swertia punicea by HPLC/DAD-ESI-MS(n). RESULTS: The fragmentation
      rules of aglycone, C-glycosides, O-glycosides, and polyxanthones with different
      linkages were summarized. The observed fragmentation pathways were used
      successfully for the analysis of the xanthone constituents of Swertia punicea,
      and a total of 34 xanthones were identified, among which 16 compounds were new
      and one compound was reported from this species for the first time. CONCLUSIONS:
      The described methods were very valuable for the identification of xanthones,
      especially of the trace compounds, and therefore could be utilized for sensitive
      and rapid qualitative analysis of xanthones in Swertia punicea.

PMID- 23136023
TI  - Electrospray ionization tandem mass spectrometry of uleine alkaloids.

PMID- 23136024
TI  - Catalytic enantioselective synthesis of alkenylhydrosilanes.

PMID- 23136027
TI  - Renal anaemia treatment in haemodialysis patients in the Central and Eastern
      European countries in everyday clinical practice follow-up.
AB  - BACKGROUND: Chronic kidney disease is almost always accompanied by anaemia.
      Erythropoietin-stimulating agents (ESA) can increase haemoglobin concentration
      and thus reduce the frequency of anaemia-related complications including the
      cardiovascular events. AIM: The aim of the study was to collect prospective data
      on 12-month standard ESA therapy used in haemodialyzed patients in selected CEE
      countries as well as on cardiovascular complications, iron status and anaemia
      treatment. PATIENTS AND METHODS: Fifty centres in 3 countries participated in the
      study. A group of 398 haemodialysed stable patients (M-231, F-167) aged 19-90
      years (57.5 +/- 14.7) on standard ESA therapy for chronic renal anaemia were
      recruited. Twelve-month prospective data on iron parameters, ESA therapy and
      cardiovascular events were collected. The use of iron, folic acid and blood
      transfusions were also assessed. Patient were divided into three groups according
      to ESA therapy start: group A-patients who received ESA after start of
      haemodialysis, group B-patients who received ESA within 3 months from the day of
      first haemodialysis and group C-patients who had received ESA more than 3 months
      before haemodialysis. Chi(2) test for qualitative data and Kruskall-Wallis test
      for quantitative data with p < 0.05 were used in statistical analysis. RESULTS:
      At prestudy period, the mean weekly dose of ESA in group C was statistically
      lower than in the remaining two groups (3,823 +/- 3,169 vs. 5,276 +/- 2,915 and
      6,427 +/- 3,441 units/week, p < 0.001), but during prospective phase of the study
      the doses did not differ among groups A, B and C. No major fluctuation of ESA
      administration schedule was observed during the study in the groups; however, at
      majority of visits, the mean frequency of ESA administration in group C was
      statistically higher than in groups A and B. At baseline visit, the haemoglobin
      concentration in group A patients (10.86 +/- 1.34 g/dL) was slightly lower than
      in group B (11.26 +/- 1.43 g/dL) and group C (10.98 +/- 1.35 g/dL) (p = 0.025),
      but at subsequent visits these differences disappeared and mean haemoglobin
      concentration was stable around 11 g/dL. Ferritin concentration increased from
      280 +/- 241 at baseline to 506 +/- 405 at month 12, and no important differences
      in the groups were observed. The other haematological parameters (haematocrit,
      iron concentration) remained stable during the entire study. The frequency of
      blood transfusion and total volume of blood in group C were lower than in groups
      A and B. During the prospective 12-month follow-up, 23 (5.8 %) of the patients
      died and 35 (8.8 %) were transplanted. No differences in death or transplantation
      rate were observed among groups A, B and C. The number of patients with adverse
      events, serious adverse events or drug-related adverse events in all groups was
      similar. In conclusion, ESA therapy increased haemoglobin concentration and no
      major differences in haematological parameters among the groups were observed
      during the entire study irrespective of early versus late start. Mortality,
      cardiovascular events or other adverse events were similar among the groups
      during the observation period; however, the limitation of the study is the sample
      size.

PMID- 23136028
TI  - Mycophenolic acid reverses IgA1 aberrant glycosylation through up-regulating
      Cosmc expression in IgA nephropathy.
AB  - OBJECTIVE: Impaired core I beta3-Gal-T-specific molecular chaperone (Cosmc)
      expression-caused IgA1 aberrant O-glycosylation is one of the main pathogeneses
      of IgA nephropathy (IgAN).This study tried to elucidate whether mycophenolic acid
      (MPA) could up-regulate Cosmc expression of peripheral lymphocytes in IgAN
      patients and reverse the dys-O-glycosylation. METHOD: Peripheral lymphocytes of
      eighteen IgAN patients and twelve normal controls were isolated and cultured for
      3-7 days with or without lipopolysaccharide (LPS) and MPA. Cosmc mRNA and protein
      expression levels were measured by real-time RT-PCR and western blot. IgA1 and O
      glycosylation level were determined by enzyme-linked immunosorbent assay (ELISA)
      and VV lectin-binding test. Correlation analysis was performed between Cosmc
      expression levels and IgA1 O-glycosylation level. RESULTS: Cosmc mRNA expression
      and IgA1 O-glycosylation level in IgAN patients were significantly lower than
      normal controls. Treatment of LPS could obviously inhibit the Cosmc expression
      and increase the IgA1 secretion in peripheral lymphocytes of IgAN patients, which
      resulted in a significantly increase in IgA1 aberrant glycosylation level.
      Addition of MPA could significantly increase the Cosmc expression level along
      with a decrease in IgA1 secretion, leading to a reverse of aberrant
      glycosylation. A significant positive correlation between the Cosmc expression
      and IgA1 O-glycosylation level was noticed. CONCLUSION: MPA can up-regulate the
      Cosmc expression and reverse the IgA1 aberrant O-glycosylation level in
      peripheral lymphocytes of IgAN patients, which might be the underlying mechanism
      of mycophenolate mofetil (MMF) therapy used in treating IgAN.

PMID- 23136029
TI  - Candidal psoas abscess following persistent pyuria in a renal transplant
      recipient.
AB  - Candidal infections occur commonly in renal transplant recipients especially in
      genitourinary system. Although the epidemiology of candiduria has not been well
      characterized in renal transplant population, it is the most common cause of
      fungal infections. However, candidal psoas abscess is very rare in the
      literature. We report a 42-year-old male renal transplant recipient with
      prolonged pyuria and candiduria followed by candidal psoas abscess formation. The
      treatment consisted of prolonged antifungal therapy along with percutaneous
      drainage. However, eventually, a surgical drainage had to be performed for the
      successful eradication.

PMID- 23136030
TI  - Podocytes proliferate: novel mechanism identified in collapsing glomerulopathies.

PMID- 23136031
TI  - The dual blockade of the renin-angiotensin system in hemodialysis patients
      requires decreased dialysate sodium concentration.
AB  - PURPOSE: The study evaluated whether the dual blockade of the renin-angiotensin
      system may influence the sodium balance in hemodialysis. METHODS: The study
      involved 148 hemodialysis patients (male 85, female 63), mean age 59.6 +/- 12.9
      years. Participants were randomly selected to receive either angiotensin
      converting enzyme inhibitor (ACEI)--subgroup A--or dual blockade ACEI and
      angiotensin receptor blocker (ARB)--subgroup AA. RESULTS: At baseline, in the A
      versus AA subgroups, the pre-dialysis sodium concentrations (mmol/l) were 137.7
      +/- 0.5 versus 137.9 +/- 0.8, the sodium gradients 2.6 +/- 0.5 versus 2.9 +/-
      0.4, interdialytic weight gain (IWG) (kg) 3.1 +/- 0.2 versus 3.0 +/- 0.3, and
      thirst inventory score (points) 18.1 +/- 1.0 versus 19.0 +/- 1.7, respectively.
      After 3 months of therapy, a decrease in sodium concentration to 134.5 +/- 0.5
      and the increase of its gradient to 5.5 +/- 0.5 were noted in the AA subgroup. An
      elevation of mean interdialytic weight gain to 3.47 +/- 0.2 and thirst score to
      21.3 +/- 2.1 was observed. No significant changes in subgroup A were found. One
      month of the dialysate sodium concentration being lowered from 140 mmol/l to 138
      mmol/l was associated with reduced serum sodium concentration and gradient,
      decreased IWG and restored moderate thirst score in the AA subgroup (137.5 +/-
      0.6 and 2.9 +/- 0.6, 3.0 +/- 0.5 and 19.2 +/- 1.3, respectively). CONCLUSIONS:
      The dual blockade of the renin-angiotensin system affects sodium balance,
      increasing the sodium gradient, thus elevating thirst sensation and enhancing
      interdialytic weight gain. In maintenance hemodialysis patients treated with both
      ACEI and ARB, lowered dialysate sodium levels should be prescribed.

PMID- 23136032
TI  - Outcome of kidney paired donation transplantation to increase donor pool and to
      prevent commercial transplantation: a single-center experience from a developing
      country.
AB  - BACKGROUND: Economic constraints in operating an effective maintenance dialysis
      program leaves renal transplantation as the only viable option for end-stage
      renal disease patients in India. Kidney paired donation (KPD) is a rapidly
      growing modality for facilitating living donor (LD) transplantation for patients
      who are incompatible with their healthy, willing LD. MATERIALS AND METHODS: The
      aim of our study was to report a single-center feasibilities and outcomes of KPD
      transplantation between 2000 and 2012. We performed KPD transplants in 70
      recipients to avoid blood group incompatibility (n = 56) or to avoid a positive
      crossmatch (n = 14). RESULTS: Over a mean follow-up of 2.72 +/- 2.96 years, one-,
      five- and ten-year patient survival were 94.6, 81, 81 %, and death-censored graft
      survival was 96.4, 90.2, 90.2 %, respectively. Ten percent of patients were lost,
      mainly due to infections (n = 4). There was 14.2 % biopsy-proven acute rejection,
      and 5.7 % interstitial fibrosis with tubular atrophy eventually leading to graft
      loss. CONCLUSION: The incidences of acute rejection, patient/graft survival rates
      were acceptable in our KPD program and, therefore, we believe it should be
      encouraged. These findings are valuable for encouraging participation of KPD
      pairs and transplant centers in national KPD program. It should be promoted in
      centers with low-deceased donor transplantation. Our study findings are relevant
      in the context of Indian government amending the Transplantation of Human Organs
      Act to encourage national KPD program. To our knowledge, it is largest single
      center report from India.

PMID- 23136033
TI  - CDK-EPI equation may be the most proper formula based on creatinine in
      determining glomerular filtration rate in Chinese patients with chronic kidney
      disease.
AB  - PURPOSE: To compare the performance of the Chronic Kidney Disease Epidemiology
      Collaboration (CDK-EPI) equation, the 24-h creatinine clearance rate (24hCCr),
      Cockroft-Gault (C-G) formula, the abbreviated Modification of Diet in Renal
      Disease (aMDRD) equation, the modified Modification of Diet in Renal Disease
      (mMDRD) equation in determining glomerular filtration rate (GFR) in Chinese
      patients with chronic kidney disease (CKD) and detect the most proper method to
      measure GFR in clinical practice. METHODS: One hundred and fifty-four patients
      with CKD were enrolled in the present study. (99m)Tc-diethylene triamine
      pentaacetic acid ((99m)Tc-DTPA) plasma clearance method measured by dual plasma
      sampling method (rGFR) was considered as the reference standard. GFR was
      estimated simultaneously using five methods: (1) CDK-EPI equation (eGFR1); (2)
      24hCCr (eGFR2); (3) C-G formula (eGFR3); (4) abbreviated MDRD equation (eGFR4);
      (5) mMDRD equation (eGFR5). The comparison of correlation, regression, bias,
      precision, accuracy, limit of agreement, and receiver-operating characteristics
      (ROC) for detecting CKD (with a GFR cutoff of 60 mL min(-1) 1.73 m(-2)) among the
      methods was analyzed to identify the most suitable method. RESULTS: All the
      equations correlated well with rGFR, and the correlation coefficient of CDK-EPI
      equation was the highest (reGFR1 = 0.922, P < 0.001). The Bland-Altman analysis
      showed that the limit of agreement for CDK-EPI equation was -25.5 to 30.3 mL min(
      1) 1.73 m(-2), which was the least range among the tested equations. The CDK-EPI
      equation represented the best capability in precision (14.24 mL min(-1) 1.73 m(
      2)). The ROC curve showed the best performance in detecting CKD. The accuracy
      within +/-30 % of CDK-EPI equation, 24hCCr, and mMDRD equation was 72.08, 69.48,
      and 70.13 %, respectively, and no statistical significant difference was found (P
      > 0.05). However, CDK-EPI equation had the highest accuracy when compared with
      the other two equations (P < 0.05). And its performance on bias showed no
      statistically significant difference compared with other four equations.
      CONCLUSIONS: Although its bias and accuracy did not overmatch the other four
      equations in our patient group, the CDK-EPI equation outperformed the other
      equations based on creatinine in correlation, precision, limit of agreement, and
      detecting CKD, and it is very simple, time-saving, and cost-effective. So we
      recommend intensely that the CDK-EPI equation is the most suitable method in
      determining GFR in Chinese patients with CKD and can be applied generally in
      clinical practice.

PMID- 23136034
TI  - MicroRNA-302 increases reprogramming efficiency via repression of NR2F2.
AB  - MicroRNAs (miRNAs) have emerged as critical regulators of gene expression through
      translational inhibition and RNA decay and have been implicated in the regulation
      of cellular differentiation, proliferation, angiogenesis, and apoptosis. In this
      study, we analyzed global miRNA and mRNA microarrays to predict novel miRNA-mRNA
      interactions in human embryonic stem cells and induced pluripotent stem cells
      (iPSCs). In particular, we demonstrate a regulatory feedback loop between the miR
      302 cluster and two transcription factors, NR2F2 and OCT4. Our data show high
      expression of miR-302 and OCT4 in pluripotent cells, while NR2F2 is expressed
      exclusively in differentiated cells. Target analysis predicts that NR2F2 is a
      direct target of miR-302, which we experimentally confirm by reporter luciferase
      assays and real-time polymerase chain reaction. We also demonstrate that NR2F2
      directly inhibits the activity of the OCT4 promoter and thus diminishes the
      positive feedback loop between OCT4 and miR-302. Importantly, higher
      reprogramming efficiencies were obtained when we reprogrammed human adipose
      derived stem cells into iPSCs using four factors (KLF4, C-MYC, OCT4, and SOX2)
      plus miR-302 (this reprogramming cocktail is hereafter referred to as "KMOS3")
      when compared to using four factors ("KMOS"). Furthermore, shRNA knockdown of
      NR2F2 mimics the over-expression of miR-302 by also enhancing reprogramming
      efficiency. Interestingly, we were unable to generate iPSCs from miR-302a/b/c/d
      alone, which is in contrast to previous publications that have reported that miR
      302 by itself can reprogram human skin cancer cells and human hair follicle
      cells. Taken together, these findings demonstrate that miR-302 inhibits NR2F2 and
      promotes pluripotency through indirect positive regulation of OCT4. This feedback
      loop represents an important new mechanism for understanding and inducing
      pluripotency in somatic cells.

PMID- 23136035
TI  - Idiopathic intracranial hypertension (pseudotumor cerebri): recognition,
      treatment, and ongoing management.
AB  - OPINION STATEMENT: Idiopathic intracranial hypertension (IIH, pseudotumor
      cerebri) is a syndrome of elevated intracranial pressure of unknown cause that
      occurs predominantly in obese women of childbearing age. It is a diagnosis of
      exclusion and, therefore, other causes of increased intracranial pressure must be
      sought with history, imaging, and cerebrospinal fluid examination before the
      diagnosis can be made. IIH produces symptoms and signs of increased intracranial
      pressure, including papilledema. If untreated, papilledema can cause progressive
      irreversible visual loss and optic atrophy. The treatment approach depends on the
      severity and time course of symptoms and visual loss, as determined by formal
      visual field testing. The main goals of treatment are alleviation of symptoms,
      including headache, and preservation of vision. All overweight IIH patients
      should be encouraged to enter a weight-management program with a goal of 5-10 %
      weight loss, along with a low-salt diet. When there is mild visual loss, medical
      treatment with acetazolamide should be initiated. Other medical treatments can be
      added or substituted when acetazolamide is insufficient as monotherapy or poorly
      tolerated. When visual loss is more severe or rapidly progressive, surgical
      interventions, such as optic nerve sheath fenestration or cerebrospinal fluid
      shunting, may be required to prevent further irreversible visual loss. The choice
      of intervention depends on the relative severity of symptoms and visual loss, as
      well as local expertise. At present, the role of transverse venous sinus stenting
      remains unclear. Although there are no evidence-based data to guide therapy,
      there is an ongoing randomized double-blind placebo-controlled treatment trial,
      investigating diet and acetazolamide therapy for IIH.

PMID- 23136036
TI  - Photochemical evidence of electronic interwall communication in double-wall
      carbon nanotubes.
AB  - Single- and double-wall carbon nanotubes (CNTs) having dimethylanilino (DMA)
      units covalently attached to the external graphene wall have been prepared by the
      reaction of the dimethylaminophenylnitronium ion with the corresponding CNT. The
      samples have been characterized by Raman and XPS spectroscopies,
      thermogravimetry, and high-resolution transmission electron microscopy in which
      the integrity of the single or double wall of the CNT and the percentage of
      substitution (one dimethylanilino group every 45 carbons of the wall for the
      single- and double-wall samples) has been determined. Nanosecond laser flash
      photolysis has shown the generation of transients that has been derived from the
      charge transfer between the dimethylanilino (as the electron donor) to the CNT
      graphene wall (as the electron acceptor). Importantly, the lifetime of the double
      wall CNT is much shorter than that monitored for the single-wall CNT. Shorter
      lived transients were also observed for the pentyl-esterified functionalized
      double-wall CNT with respect to the single-wall analogue in the presence of hole
      (CH(3)OH) and electron quenchers (O(2), N(2)O), which has led to the conclusion
      that the inner, intact graphene wall that is present in double-wall CNT increases
      the charge mobility significantly, favoring charge recombination processes.
      Considering the importance that charge mobility has in microelectronics, our
      finding suggests that double-wall CNT or two-layer graphene may be more
      appropriate to develop devices needing fast charge mobility.

PMID- 23136037
TI  - Synovitis--an inflammation of joints destroying the bone.
AB  - This article is to share some of the key scientific insights made by Dr Barry
      Bresnihan in rheumatoid arthritis. Dr Bresnihan  elaborated new and visionary
      concepts in arthritis research, which still influence current thinking. He had
      been particularly dedicated to investigate the inflammatory tissue (synovitis) in
      RA, which he considered as a clue to understand the pathogenesis of this disease.
      He thereby pioneered the concept of synovial biopsy as a technique, which allows
      to directly analyse synovitis and has  stimulated many other rheumatologists in
      joining his efforts. He was also dedicated to understand why synovitis triggers
      bone destruction in joints and started to work on defining the molecular
      interactions between inflammation and the bone. This article picks up some of the
      major insights achieved by Dr Bresnihan's work and how these findings influenced
      today's understanding of arthritis.

PMID- 23136038
TI  - Match criteria for human cell line authentication: where do we draw the line?
AB  - Continuous human cell lines have been used extensively as models for biomedical
      research. In working with these cell lines, researchers are often unaware of the
      risk of cross-contamination and other causes of misidentification. To reduce this
      risk, there is a pressing need to authenticate cell lines, comparing the sample
      handled in the laboratory to a previously tested sample. The American Type
      Culture Collection Standards Development Organization Workgroup ASN-0002 has
      developed a Standard for human cell line authentication, recommending short
      tandem repeat (STR) profiling for authentication of human cell lines. However,
      there are known limitations to the technique when applied to cultured samples,
      including possible genetic drift with passage. In our study, a dataset of 2,279
      STR profiles from four cell banks was used to assess the effectiveness of the
      match criteria recommended within the Standard. Of these 2,279 STR profiles,
      1,157 were grouped into sets of related cell lines-duplicate holdings,
      legitimately related samples or misidentified cell lines. Eight core STR loci
      plus amelogenin were used to unequivocally authenticate 98% of these related
      sets. Two simple match algorithms each clearly discriminated between related and
      unrelated samples, with separation between related samples at >=80% match and
      unrelated samples at <50% match. A small degree of overlap was noted at 50-79%
      match, mostly from cell lines known to display variable STR profiles. These match
      criteria are recommended as a simple and effective way to interpret results from
      STR profiling of human cell lines.

PMID- 23136039
TI  - Detecting local immunoglobulin E from mucosal brush biopsy of the inferior
      turbinates using microarray analysis.
AB  - BACKGROUND: It has been previously demonstrated that local, antigen-specific
      immunoglobulin E (IgE) can be detected using a standard in vitro assay of lysed
      epithelial cells in saline, harvested via nasal mucosal brush biopsy (MBB).
      However, compared to surgical biopsy or serum, smaller amounts of IgE are
      harvested using MBB, making detection much more difficult. Microarray analysis
      (MA) requires less IgE for detection, making this an attractive option for MBB.
      The goals of this study were to compare MA to a standard IgE assay for detecting
      antigen-specific IgE from MBB and to test the association between the presence of
      multiple positive components on MA with specific IgE on standard assay and skin
      prick testing (SPT) grade. METHODS: MBB samples from 18 allergic rhinitis
      patients, which were previously tested for antigen-specific IgE to common
      airborne allergens using a standard IgE assay, underwent MA for antigen-specific
      IgE to multiple components of airborne and food allergens. Fisher's exact
      probability testing was used to measure the strength of association between the 2
      testing modalities for Timothy grass, ragweed, cat, Alternaria, and D. farinae.
      RESULTS: MA correlated very highly with standard assay (p < 0.0001) and 50% of
      positive antigens on MA detected multiple components to that antigen. The
      presence of multiple components was not associated with specific IgE levels on
      standard assay or SPT grade. CONCLUSION: This is the first demonstration that
      antigen-specific IgE in saline samples can be measured using MA. The ability of
      MA to measure smaller amounts of IgE, with similar accuracy, may give it a
      potential advantage for MBB analysis in the future.

PMID- 23136040
TI  - Research results: preserving newborn blood samples.
AB  - Retention and use, without explicit parental permission, of residual dried blood
      samples from newborn screening has generated public controversy over concerns
      about violations of family privacy rights and loss of parental autonomy. The
      public debate about this issue has included little discussion about the
      destruction of a potentially valuable public resource that can be used for
      research that may yield improvements in public health. The research community
      must advocate for policies and infrastructure that promote retention of residual
      dried blood samples and their use in biomedical research.

PMID- 23136041
TI  - Improving risk assessment.
AB  - Widespread sharing and analysis of clinical trial data and a U.S. government
      initiative to engineer nonclinical cell-based models that mimic human biological
      processes have the potential to improve predictions of drug-related adverse
      events.

PMID- 23136042
TI  - A human disease model of drug toxicity-induced pulmonary edema in a lung-on-a
      chip microdevice.
AB  - Preclinical drug development studies currently rely on costly and time-consuming
      animal testing because existing cell culture models fail to recapitulate complex,
      organ-level disease processes in humans. We provide the proof of principle for
      using a biomimetic microdevice that reconstitutes organ-level lung functions to
      create a human disease model-on-a-chip that mimics pulmonary edema. The
      microfluidic device, which reconstitutes the alveolar-capillary interface of the
      human lung, consists of channels lined by closely apposed layers of human
      pulmonary epithelial and endothelial cells that experience air and fluid flow, as
      well as cyclic mechanical strain to mimic normal breathing motions. This device
      was used to reproduce drug toxicity-induced pulmonary edema observed in human
      cancer patients treated with interleukin-2 (IL-2) at similar doses and over the
      same time frame. Studies using this on-chip disease model revealed that
      mechanical forces associated with physiological breathing motions play a crucial
      role in the development of increased vascular leakage that leads to pulmonary
      edema, and that circulating immune cells are not required for the development of
      this disease. These studies also led to identification of potential new
      therapeutics, including angiopoietin-1 (Ang-1) and a new transient receptor
      potential vanilloid 4 (TRPV4) ion channel inhibitor (GSK2193874), which might
      prevent this life-threatening toxicity of IL-2 in the future.

PMID- 23136043
TI  - An orally active TRPV4 channel blocker prevents and resolves pulmonary edema
      induced by heart failure.
AB  - Pulmonary edema resulting from high pulmonary venous pressure (PVP) is a major
      cause of morbidity and mortality in heart failure (HF) patients, but current
      treatment options demonstrate substantial limitations. Recent evidence from
      rodent lungs suggests that PVP-induced edema is driven by activation of pulmonary
      capillary endothelial transient receptor potential vanilloid 4 (TRPV4) channels.
      To examine the therapeutic potential of this mechanism, we evaluated TRPV4
      expression in human congestive HF lungs and developed small-molecule TRPV4
      channel blockers for testing in animal models of HF. TRPV4 immunolabeling of
      human lung sections demonstrated expression of TRPV4 in the pulmonary vasculature
      that was enhanced in sections from HF patients compared to controls. GSK2193874
      was identified as a selective, orally active TRPV4 blocker that inhibits Ca(2+)
      influx through recombinant TRPV4 channels and native endothelial TRPV4 currents.
      In isolated rodent and canine lungs, TRPV4 blockade prevented the increased
      vascular permeability and resultant pulmonary edema associated with elevated PVP.
      Furthermore, in both acute and chronic HF models, GSK2193874 pretreatment
      inhibited the formation of pulmonary edema and enhanced arterial oxygenation.
      Finally, GSK2193874 treatment resolved pulmonary edema already established by
      myocardial infarction in mice. These findings identify a crucial role for TRPV4
      in the formation of HF-induced pulmonary edema and suggest that TRPV4 blockade is
      a potential therapeutic strategy for HF patients.

PMID- 23136044
TI  - Human melanoma metastasis in NSG mice correlates with clinical outcome in
      patients.
AB  - Studies of human cancer metastasis have been limited by a lack of experimental
      assays in which cancer cells from patients metastasize in vivo in a way that
      correlates with clinical outcome. This makes it impossible to study intrinsic
      differences in the metastatic properties of cancers from different patients. We
      recently developed an assay in which human melanomas readily engraft in nonobese
      diabetic/severe combined immunodeficient interleukin-2 receptor-gamma chain null
      (NSG) mice. We show that melanomas from 25 patients exhibited reproducible
      differences in the rate of spontaneous metastasis after transplantation into NSG
      mice and that these differences correlated with clinical outcome in the patients.
      Stage IIIB/C melanomas that formed distant metastases within 22 months in
      patients also formed tumors that metastasized widely in NSG mice, whereas stage
      IIIB/C melanomas that did not form distant metastases within 22 to 50 months in
      patients metastasized more slowly in NSG mice. These differences in the
      efficiency of metastasis correlated with the presence of circulating melanoma
      cells in the blood of NSG mice, suggesting that the rate of entry into the blood
      is one factor that limits the rate of metastasis. The study of NSG mice can
      therefore yield information about the metastasis of human melanomas in vivo, in
      this case revealing intrinsic differences among stage III melanomas in their
      ability to circulate/survive in the blood and to metastasize.

PMID- 23136045
TI  - Alcohol dehydrogenase isoenzymes nomenclature.

PMID- 23136046
TI  - Green tea extract co-administered with a polymer effectively prevents alcoholic
      liver damage by prolonged inhibition of alcohol absorption in mice.
AB  - AIMS: Alcohol toxicity can induce multiple organ dysfunction, including the
      liver. Gallated catechins (GCs), the components of green tea extract (GTE), have
      been known to inhibit intestinal lipid absorption. This study was designed to
      investigate the inhibitory effect of GC on the absorption of the lipid-soluble
      ethanol in normal mice. In addition, the effectiveness of prolonging the GC
      mediated effect was evaluated as a means of preventing alcoholic liver damage.
      METHODS: GTE was administered orally immediately or 90 min before ethanol
      administration and the blood ethanol and acetaldehyde levels were measured. Binge
      ethanol administration (by gavage every 6 h for 24 h) was used to induce acute
      liver injury, and GTE was administered 90 min prior to every ethanol
      administration. RESULTS: When GTE, but not GC-decreased GTE, was administered
      immediately before ethanol intake, the blood ethanol and acetaldehyde levels were
      significantly lower than those in the control. On the other hand, GTE has no
      effect when GTE was administered 90 min before ethanol intake. When GTE was co
      administered with polyethylene glycol (PEG) or poly-gamma-glutamate (PGA) 90 min
      before ethanol intake, the lowering effect of GTE on the blood ethanol and
      acetaldehyde levels was maintained in contrast to the GTE-alone-treated group.
      After binge ethanol administration, liver weight decreased, and serum alanine
      aminotransferase and aspartate aminotransferase levels were elevated.
      Additionally, histopathological changes, such as macrovesicular steatosis and
      necrosis, were induced in the liver, together with reactive oxygen species
      generation. When GTE + PEG or GTE + PGA, but not GTE alone, was administered 90
      min before ethanol intake, acute liver injury was ameliorated. CONCLUSION: These
      findings support the development of GTE + PEG or GTE + PGA as an inhibitor of
      intestinal alcohol absorption for the preventative treatment of acute alcohol
      toxicity.

PMID- 23136047
TI  - Highly reactive, single-component nickel catalyst precursor for Suzuki-Miyuara
      cross-coupling of heteroaryl boronic acids with heteroaryl halides.

PMID- 23136048
TI  - Remarkable mobility increase and threshold voltage reduction in organic field
      effect transistors by overlaying discontinuous nano-patches of charge-transfer
      doping layer on top of semiconducting film.
AB  - An effective strategy for significantly increasing the organic transistor
      mobility with simultaneous reduction of the threshold voltage utilizing
      discontinuous nano-patches of charge-transfer doping layer is demonstrated. By
      overlaying the nano-patches on top of a given semiconducting film, mobility and
      threshold voltage of p-type pentacene are remarkably improved to 4.52 cm(2) V(-1)
      s(-1) and -0.4 V, and those of n-type Hex-4-TFPTA are also improved to 2.57 cm(2)
      V(-1) s(-1) and 4.1 V.

PMID- 23136049
TI  - Antibacterial and membrane-damaging activities of beta-bungarotoxin B chain.
AB  - This study investigates whether the B chain of beta-bungarotoxin exerted
      antibacterial activity against Escherichia coli (Gram-negative bacteria) and
      Staphylococcus aureus (Gram-positive bacteria) via its membrane-damaging
      activity. The B chain exhibited a growth inhibition effect on E. coli but did not
      show a bactericidal effect on S. aureus. The B-chain bactericidal action on E.
      coli positively correlated with an increase in membrane permeability in the
      bacterial cells. Lipopolysaccharide (LPS) layer destabilization and lipoteichoic
      acid (LTA) biosynthesis inhibition in the cell wall increased the B-chain
      bactericidal effect on E. coli and S. aureus. The B chain induced leakage and
      fusion in E. coli and S. aureus membrane-mimicking liposomes. Compared with LPS,
      LTA notably suppressed the membrane-damaging activity and fusogenicity of the B
      chain. The B chain showed similar binding affinity with LPS and LTA, whereas LPS
      and LTA binding differently induced B-chain conformational change as evidenced by
      the circular dichroism spectra. Taken together, our data indicate that the
      antibacterial action of the B chain is related to its ability to induce membrane
      permeability and suggest that the LPS-induced and LTA-induced B-chain
      conformational change differently affects the bactericidal action of the B chain.

PMID- 23136050
TI  - Effect of C7 modifications on benzothiadiazine-1,1-dioxide derivatives on their
      inhibitory activity and selectivity toward aldose reductase.
AB  - The development and progression of chronic complications in diabetic patients,
      such as retinopathy, nephropathy, neuropathy, cataracts, and stroke, are related
      to the activation and/or overexpression of aldose reductase (ALR2), which is a
      member of the aldo-keto reductase superfamily. A structure-activity relationship
      study focused on the C7 position of 1,2,4-benzothiadiazine-1,1-dioxide
      derivatives was pursued in an attempt to discover ALR2 inhibitors with enhanced
      potency and selectivity. These studies led to a series of new C7-substituted
      compounds, which were evaluated for their inhibitory activity against ALR2; they
      exhibited IC(50) values in the range of 2.80-45.13 nM. Two compounds with a C7
      dimethylcarbamoyl and a C7-diethylcarbamoyl substituent, respectively, were found
      to be the most active and presented excellent selectivity for ALR2 over aldehyde
      reductase (ALR1). The structure-activity relationship analyses and molecular
      modeling studies presented herein highlight the importance of hydrophobic and
      bulky groups at the C7 position for inhibitory activity and selectivity toward
      ALR2.

PMID- 23136051
TI  - Uncontrolled arterial hypertension in primary care--patient characteristics and
      associated factors.
AB  - PRINCIPLES: Most patients with arterial hypertension are treated in primary care.
      The objective is to assess characteristics of patients with uncontrolled arterial
      hypertension and its associated determinants in Swiss primary care. METHOD: Data
      on 122 adult patients with uncontrolled hypertension (mm Hg >140 systolic and/or
      >90 diastolic) was collected from the baseline data of the on-going randomised
      controlled "CoCo" trial: Colour-coded Blood Pressure Control. Patient and general
      practitioner characteristics were analysed to investigate the relationship
      between BP and patient characteristics. RESULTS: From October 2009 to March 2011
      30 general practitioners recruited 122 patients; median age 64 years (IQR 54.8
      72), 50% male, median BMI 28.3 kg/m2 (IQR 25.3-31.7), 21.5% smokers. 65.6%
      performed home blood pressure measurement, 88.5% received pharmacological
      treatment, 41.8% mono-therapy. Most frequent dual drug combinations:
      diuretics/angiotensin-receptor-blockers (33.3%), angiotensin-converting-enzyme
      inhibitors/beta blockers (both 28.1%). BMI, smoking and age were independent
      predictors for elevated systolic blood pressure when controlled for gender, home
      blood pressure measurement, education, pulse rate and number of antihypertensive
      substances. We found a significant non-linear association between systolic blood
      pressure and number of antihypertensive substances. Age and any amount of
      antihypertensive substances were independently and inversely correlated with
      diastolic blood pressure. The findings did not change when additionally
      controlled for general practitioner clustering effect. CONCLUSION: Smoking and
      high BMI are strong and independent factors associated with higher blood pressure
      levels in patients with uncontrolled arterial hypertension. A high rate of
      monotherapy and a decrease in the incremental gain on blood pressure control when
      more antihypertensive agents are used highlight the importance of adequate
      pharmacological treatment as well as risk factor control.

PMID- 23136052
TI  - Contrast induced exacerbation of renal dysfunction in the advanced chronic kidney
      disease.
AB  - Contrast media affects renal function, especially in the patients with advanced
      chronic kidney disease (CKD). The aim of this study was to investigate the
      characteristics of contrast induced exacerbation of renal dysfunction in the
      patients with advanced CKD (estimated glomerular filtration rate <30 ml/min/1.73
      m(2)). We enrolled 102 advanced CKD patients who underwent cardiac
      catheterization. Delta creatinine (post-catheterization creatinine minus pre
      catheterization creatinine) were calculated. The patients were divided into three
      groups according to delta creatinine. The highest tertile of the delta creatinine
      was defined as the exacerbation group. Multivariate logistic regression analyses
      were performed to find the characteristics of the exacerbation group. Anemia
      (odds ratio (OR): 15.53, 95% Confidence Interval (95%CI): 1.81-133.27, p = 0.01)
      and proteinuria (OR: 5.91, 95%CI: 1.64-21.28, p < 0.01) were significant
      characteristics of the exacerbation group after adjusting confounding factors. In
      conclusion, anemia and proteinuria were associated with contrast induced
      exacerbation of renal dysfunction in the advanced CKD patients.

PMID- 23136053
TI  - A green approach to ethyl acetate: quantitative conversion of ethanol through
      direct dehydrogenation in a Pd-Ag membrane reactor.
AB  - Pincers do the trick: The conversion of ethanol to ethyl acetate and hydrogen was
      achieved using a pincer-Ru catalyst in a Pd-Ag membrane reactor. Near
      quantitative conversions and yields could be achieved without the need for acid
      or base promoters or hydrogen acceptors (see scheme).

PMID- 23136054
TI  - In vitro potency and efficacy favor later generation fluoroquinolones for
      treatment of canine and feline Escherichia coli uropathogens in the United
      States.
AB  - Information regarding in vitro activity of newer fluoroquinolones (FQs) is
      limited despite increasing resistance in canine or feline pathogenic Escherichia
      coli (E. coli). This study describes in vitro potency and efficacy toward E. coli
      of seven FQs grouped according to similarities in chemical structure:
      enrofloxacin, ciprofloxacin, orbifloxacin (first-group), levofloxacin,
      marbofloxacin (second-group) and pradofloxacin, moxifloxacin (third-group; latest
      S, S-pyrrolidino-piperidine at C-7). Potency measures included minimum inhibitory
      concentration (MIC) (geometric mean MIC, MIC(50), MIC(90)); and mutant prevention
      concentration (MPC) for FQ susceptible isolates only. In vitro efficacy measures
      included relative susceptibility (MIC(BP-S):MIC) or resistance (MIC:MIC(BP-R))
      and mutant selection window (MSW) (MPC:MIC). For enrofloxacin susceptible
      isolates, mean MIC (MUg/ml) was least for each third-group drug and ciprofloxacin
      and greatest for enrofloxacin and orbifloxacin (P = 0.006). For enrofloxacin
      susceptible isolates, MPC were below MIC:MIC(BP-R) and least for pradofloxacin
      (0.29 +/- 0.16 MUg/ml) and greatest for enrofloxacin (1.55 +/- 0.55 MUg/ml) (P =
      0.006). MSW was least for pradofloxacin (55 +/- 30) and greatest for
      ciprofloxacin (152 +/- 76) (P = 0.0024). MIC(BP-S):MIC was greatest (P = 0.025)
      for pradofloxacin (190.1 +/- 0.61) and least for enrofloxacin (23.53 +/- 0.83).
      For FQ susceptible isolates, FQs MIC:MIC(BP-R) may serve as a surrogate for MPC.
      Because in vitro efficacy was greatest for pradofloxacin; it might be preferred
      for treatment of urinary tract infections (UTIs) associated with FQ susceptible
      E. coli uropathogens.

PMID- 23136055
TI  - Expression of glycoproteins bearing complex human-like glycans with galactose
      terminal in Hansenula polymorpha.
AB  - Glycoproteins derived from Hansenula polymorpha can not be used for therapeutic
      purposes due to their high-mannose type asparagine-linked (N-linked) glycans,
      which result in immune reactions and poor pharmacokinetic behaviors in human
      body. Previously, we reported that the trimannosyl core N-linked glycans
      (Man(3)GlcNAc(2)) intermediate can be generated in endoplasmic reticulum in
      HpALG3 and HpALG11 double-mutant H. polymorpha. Here, we describe the further
      modification of the glycosylation pathway in this double-defect strain to express
      glycoproteins with complex human-like glycans. After eliminating the impact of
      HpOCH1, three glycosyltransferases were introduced into this triple-mutant
      strain. When human beta-1,2-N-acetylglucosaminyltransferase I (hGnTI) was
      efficiently targeted in early Golgi, more than 95 % glycans attached to the
      glycoproteins were added one N-acetylglucosamine (GlcNAc). With subsequently
      introduction of rat beta-1,2-N-acetylglucosaminyltransferase II (rGnTII) and
      human beta-1,4-galactosyltransferase I (hGalTI), several glycoengineered strains
      can produce glycoproteins bearing glycans with terminal N-acetylglucosamine or
      galactose. The expression of glycoproteins with glycan
      Gal(2)GlcNAc(2)Man(3)GlcNAc(2) represents a significant step toward the ability
      to express fully humanized glycoproteins in H. polymorpha. Furthermore, several
      shake-flask and bioreactor fermentation experiments indicated that, although the
      cells do display a reduction in growth rate, the glycoengineered strains are
      still suitable for high-density fermentation.

PMID- 23136056
TI  - Interactions between chemical and climate stressors: a role for mechanistic
      toxicology in assessing climate change risks.
AB  - Incorporation of global climate change (GCC) effects into assessments of chemical
      risk and injury requires integrated examinations of chemical and nonchemical
      stressors. Environmental variables altered by GCC (temperature, precipitation,
      salinity, pH) can influence the toxicokinetics of chemical absorption,
      distribution, metabolism, and excretion as well as toxicodynamic interactions
      between chemicals and target molecules. In addition, GCC challenges processes
      critical for coping with the external environment (water balance,
      thermoregulation, nutrition, and the immune, endocrine, and neurological
      systems), leaving organisms sensitive to even slight perturbations by chemicals
      when pushed to the limits of their physiological tolerance range. In simplest
      terms, GCC can make organisms more sensitive to chemical stressors, while
      alternatively, exposure to chemicals can make organisms more sensitive to GCC
      stressors. One challenge is to identify potential interactions between
      nonchemical and chemical stressors affecting key physiological processes in an
      organism. We employed adverse outcome pathways, constructs depicting linkages
      between mechanism-based molecular initiating events and impacts on individuals or
      populations, to assess how chemical- and climate-specific variables interact to
      lead to adverse outcomes. Case examples are presented for prospective scenarios,
      hypothesizing potential chemical-GCC interactions, and retrospective scenarios,
      proposing mechanisms for demonstrated chemical-climate interactions in natural
      populations. Understanding GCC interactions along adverse outcome pathways
      facilitates extrapolation between species or other levels of organization,
      development of hypotheses and focal areas for further research, and improved
      inputs for risk and resource injury assessments.

PMID- 23136057
TI  - Office-based balloon sinus dilation: a prospective, multicenter study of 203
      patients.
AB  - BACKGROUND: Balloon sinus dilation (BSD) is an increasingly used tool in
      endoscopic sinus surgery (ESS). The tissue-sparing nature of the instrumentation
      allows for properly selected patients to undergo office-based procedures under
      local anesthesia. METHODS: This was an Institutional Review Board (IRB)-approved,
      prospective, 14-center trial. Patients (n = 203) requiring ESS for medically
      refractory chronic sinusitis underwent transnasal BSD treatment in an office
      setting under local anesthesia. Safety, tolerability, technical success, clinical
      efficacy (20-item Sino-Nasal Outcome Test [SNOT-20]), and radiographic outcome
      (Lund-Mackay [LMK] score) of ESS with BSD in the office setting were assessed.
      Subjects were followed at 2, 8, and 24 weeks. RESULTS: A total of 552 sinuses
      were dilated in 203 patients: 47.6% maxillaries, 45.5% frontals, and 6.9%
      sphenoids. Seventy-seven patients were revisions of prior ESS. The mean number of
      sinuses dilated per subject was 2.7. Technical dilation success was 93.3%, 90.5%,
      and 93.7% for maxillary, sphenoid, and frontal sinuses, respectively. SNOT-20 and
      LMK computed tomography (CT) scoring showed statistically significant improvement
      at 24 weeks (p < 0.0001) and clinically significant improvement in quality of
      life. The procedure was reported as tolerable or highly tolerable by 82.3% of
      patients. There were 0.15 postoperative debridements per patient and the majority
      returned to normal activity within 48 hours. One (0.5%) procedure-related adverse
      event related to periorbital swelling was reported, which spontaneously resolved
      shortly after the procedure without further sequelae. CONCLUSION: Performance of
      ESS with BSD in the office under local anesthesia is feasible, well-tolerated,
      safe, and effective. Twenty-four week follow-up demonstrates clinical and
      statistical improvement in patient quality of life and radiographic outcomes.

PMID- 23136058
TI  - The crossover sign overestimates acetabular retroversion.
AB  - BACKGROUND: The crossover sign is a radiographic finding associated with cranial
      acetabular retroversion and has been associated with pincer-type femoroacetabular
      impingement (FAI) in patients with hip pain. Variable morphology, location, and
      size of the anterior inferior iliac spine (AIIS) may contribute to the crossover
      sign even in the absence of retroversion. Thus, the sign may overestimate the
      incidence of acetabular retroversion. QUESTIONS/PURPOSES: We asked: Can the
      crossover sign appear on standardized, well-positioned AP pelvis radiographs
      despite the absence of acetabular retroversion? And what is the contribution of
      variable size and morphology of the AIIS to a crossover sign? METHODS: We
      evaluated radiographs of 53 patients with symptomatic FAI in the absence of
      substantial chondral degenerative changes (< Tonnis Grade 2). Forty-one
      radiographs met the appropriate criteria of neutral tilt and obliquity. Three
      independent reviewers determined presence and location of the crossover sign.
      Acetabular version was defined using high-resolution three-dimensional CT. CT
      reconstructions were used to define three AIIS types addressing AIIS morphology.
      RESULTS: Nineteen of 38 radiographs with a crossover sign on AP radiographs had
      focal or global acetabular retroversion on three-dimensional CT (positive and
      negative predictive values = 50%). In contrast, the AIIS extended to or below the
      level of the anterior superior acetabular rim and was partially or completely
      responsible for the appearance of a radiographic crossover sign in all 19 hips
      with an anteverted acetabulum. High interobserver reliability (kappa > 0.8) was
      found for AIIS types. CONCLUSIONS: A crossover sign is frequently present on well
      positioned AP pelvis radiographs in the absence of acetabular retroversion.
      Variable AIIS morphology may explain the appearance of this sign in the presence
      or absence of acetabular retroversion.

PMID- 23136060
TI  - Integrated and segregated Au/gamma-Fe2O3 binary nanoparticle assemblies.

PMID- 23136059
TI  - Geographical distribution and oncogenic risk association of human papillomavirus
      type 58 E6 and E7 sequence variations.
AB  - Human papillomavirus (HPV) 58 accounts for a notable proportion of cervical
      cancers in East Asia and parts of Latin America, but it is uncommon elsewhere.
      The reason for such ethnogeographical predilection is unknown. In our study,
      nucleotide sequences of E6 and E7 genes of 401 HPV58 isolates collected from 15
      countries/cities across four continents were examined. Phylogenetic relationship,
      geographical distribution and risk association of nucleotide sequence variations
      were analyzed. We found that the E6 genes of HPV58 variants were more conserved
      than E7. Thus, E6 is a more appropriate target for type-specific detection,
      whereas E7 is more appropriate for strain differentiation. The frequency of
      sequence variation varied geographically. Africa had significantly more isolates
      with E6-367A (D86E) but significantly less isolates with E6-203G, -245G, -367C
      (prototype-like) than other regions (p <= 0.003). E7-632T, -760A (T20I, G63S) was
      more frequently found in Asia, and E7-793G (T74A) was more frequent in Africa (p
      < 0.001). Variants with T20I and G63S substitutions at E7 conferred a
      significantly higher risk for cervical intraepithelial neoplasia grade III and
      invasive cervical cancer compared to other HPV58 variants (odds ratio = 4.44, p =
      0.007). In conclusion, T20I and/or G63S substitution(s) at E7 of HPV58 is/are
      associated with a higher risk for cervical neoplasia. These substitutions are
      more commonly found in Asia and the Americas, which may account for the higher
      disease attribution of HPV58 in these areas.

PMID- 23136061
TI  - Single-step formation of graphene on dielectric surfaces.
AB  - The direct formation of graphene on various dielectric surfaces is successful via
      a single-step rapid thermal processing (RTP) of substrates coated with amorphous
      carbon (C) and nickel (Ni) thin films. High-quality graphene is obtained
      uniformly on the whole surface of wafers with a controlled number of graphene
      layers. The monolayer graphene exhibits a low sheet resistance and a high optical
      transmittance in the visible range.

PMID- 23136062
TI  - How is (68)Ga labeling of macrocyclic chelators influenced by metal ion
      contaminants in (68)Ge/(68)Ga generator eluates?
AB  - To assess the influence of Zn(2+) , Cu(2+) , Fe(3+) , Al(3+) , Ti(IV) , and
      Sn(IV)  on incorporation of (68) Ga(3+)  into pendant-arm macrocyclic chelators,
      the (68) Ga labeling of 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA),
      1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), 1,4,7
      triazacyclononane-1,4,7-tris[methyl(2-carboxyethyl)phosphinic acid]) (TRAP), and
      1,4,7-triazacyclononane-1-[methyl(2-carboxyethyl)phosphinic acid]-4,7
      bis[methyl(2-hydroxymethyl)phosphinic acid] (NOPO), as well as their peptide
      conjugates, was investigated in the presence of varying concentrations of these
      metal ions. The (68) Ga labeling yield for carboxylate-type chelators NOTA and
      DOTA is decreased at lower metal ion contaminant concentrations compared with
      phosphinate-type chelators TRAP and NOPO. The latter are able to rapidly exchange
      coordinated Zn(II)  with (68) Ga(3+) , as confirmed by mass spectrometry and (31)
      P NMR spectroscopy. (68) Ga labeling of Zn(II)  complexes of TRAP and NOPO
      proceeds as efficient as labeling of neat NOTA; this applies also to the
      corresponding peptide conjugates of these chelators. This behavior results in
      substantially improved selectivity for Ga(3+)  and, therefore, in more robust and
      reliable (68) Ga labeling procedures. In addition, none of the investigated
      chelators binds (68) Ge, rendering post-labeling purification protocols, for
      example, solid-phase extraction, a reliable means of removal of (68) Ge
      contamination from (68) Ga radiopharmaceuticals.

PMID- 23136063
TI  - Oxidative burst inhibitory and cytotoxic activity of constituents of the fruits
      of Odyendyea gabonensis.
AB  - The methanol extract of dried fruits of Odyendyea gabonensis afforded one new
      quassinoid [(-)-odyendanol (1)], one new canthin-6-one alkaloid [9-hydroxy-5
      methoxycanthin-6-one (4)], and two new steroids [22E, 24R-stigmasta-5,22-diene
      3,7-dione (7) and 22E,24R-stigmast-22-ene-3,7-dione (8)] along with fourteen
      known compounds. The structures of all compounds were established by analyzing
      the spectroscopic data. The 13C-NMR values of (-)-odyendene (2) and (-)-odyendane
      (3), as well as the single-crystal X-ray structure of 5-methoxycanthin-6-one (6)
      are also reported.The oxidative burst inhibitory activity of pure compounds 1-12
      was determined by the chemoluminescence assay, and cytotoxic activities of
      compounds 2-6 against the human prostate cancer cell PC-3 line were evaluated.
      Compounds 1-6 exhibited a clear suppressive effect on the phagocytosis response
      upon activation with serum-opsonized zymosan in the range of IC50 = 0.9-2.0 uM
      versus ibuprofen with IC50 = 12.1 uM, while all canthin-6-one alkaloids (4-6)
      displayed moderate cytotoxic activity against the human prostate cancer cell PC-3
      line, with IC50 values ranging from 13.5-15.4 uM versus doxorubicine with IC50 =
      1.5 uM.

PMID- 23136064
TI  - Vitex agnus-castus extracts for female reproductive disorders: a systematic
      review of clinical trials.
AB  - Vitex agnus-castus L. (chaste tree; chasteberry) is a popular herbal treatment,
      predominantly used for a range of female reproductive conditions in Anglo
      American and European practice. The objective of this systematic review was to
      evaluate the evidence for the efficacy and safety of Vitex extracts from
      randomised, controlled trials investigating women's health.Eight databases were
      searched using Latin and common names for Vitex and phytotherapeutic preparations
      of the herb as a sole agent, together with filters for randomised, controlled
      trials or clinical trials. Methodological quality was assessed according to the
      Cochrane risk of bias and Jadad scales, as well as the proposed elaboration of
      CONSORT for reporting trials on herbal interventions.Thirteen randomised,
      controlled trials were identified and twelve are included in this review, of
      which eight investigated premenstrual syndrome, two premenstrual dysphoric
      disorder, and two latent hyperprolactinaemia. For premenstrual syndrome, seven of
      eight trials found Vitex extracts to be superior to placebo (5 of 6 studies),
      pyridoxine (1), and magnesium oxide (1). In premenstrual dysphoric disorder, one
      study reported Vitex to be equivalent to fluoxetine, while in the other,
      fluoxetine outperformed Vitex. In latent hyperprolactinaemia, one trial reported
      it to be superior to placebo for reducing TRH-stimulated prolactin secretion,
      normalising a shortened luteal phase, increasing mid-luteal progesterone and
      17beta-oestradiol levels, while the other found Vitex comparable to bromocriptine
      for reducing serum prolactin levels and ameliorating cyclic mastalgia. Adverse
      events with Vitex were mild and generally infrequent. The methodological quality
      of the included studies varied, but was generally moderate-to-high. Limitations
      include small sample sizes in some studies, heterogeneity of conditions being
      treated, and a range of reference treatments.Despite some methodological
      limitations, the results from randomised, controlled trials to date suggest
      benefits for Vitex extracts in the treatment of premenstrual syndrome,
      premenstrual dysphoric disorder and latent hyperprolactinaemia. Further research
      is recommended, and greater transparency in reporting for future trials.

PMID- 23136065
TI  - A versatile building block: the structures and functions of negative-sense single
      stranded RNA virus nucleocapsid proteins.
AB  - Nucleocapsid protein (NPs) of negative-sense single-stranded RNA (-ssRNA) viruses
      function in different stages of viral replication, transcription, and maturation.
      Structural investigations show that -ssRNA viruses that encode NPs preliminarily
      serve as structural building blocks that encapsidate and protect the viral
      genomic RNA and mediate the interaction between genomic RNA and RNA-dependent RNA
      polymerase. However, recent structural results have revealed other biological
      functions of -ssRNA viruses that extend our understanding of the versatile roles
      of virally encoded NPs.

PMID- 23136066
TI  - Intersection of autophagy with pathways of antigen presentation.
AB  - Traditionally, macroautophagy (autophagy) is viewed as a pathway of cell
      survival. Autophagy ensures the elimination of damaged or unwanted cytosolic
      components and provides a source of cellular nutrients during periods of stress.
      Interestingly, autophagy can also directly intersect with, and impact, other
      major pathways of cellular function. Here, we will review the contribution of
      autophagy to pathways of antigen presentation. The autophagy machinery acts to
      modulate both MHCI and MHCII antigen presentation. As such autophagy is an
      important participant in pathways that elicit host cell immunity and the
      elimination of infectious pathogens.

PMID- 23136068
TI  - Endoreduplication intensity as a marker of seed developmental stage in the
      Fabaceae.
AB  - Flow cytometry (FCM) can be used to study cell cycle activity in developing,
      mature and germinating seeds. It provides information about a seed's
      physiological state and therefore can be used by seed growers for assessing
      optimal harvest times and presowing treatments. Because an augmented proportion
      of 4C nuclei usually is indicative of high mitotic activity, the 4C/2C ratio is
      commonly used to follow the progress of seed development and germination.
      However, its usefulness for polysomatic (i.e., containing cells with different
      DNA content) seeds is questioned. Changes in cell cycle/endoreduplication
      activity in developing seeds of five members of the Fabaceae were studied to
      determine a more suitable marker of seed developmental stages for polysomatic
      species based on FCM measurements. Seeds of Phaseolus vulgaris, Medicago sativa,
      Pisum sativum, Vicia sativa, and Vicia faba var. minor were collected 20, 30, 40,
      50, and 60 days after flowering (DAF), embryos were isolated and the proportion
      of nuclei with different DNA contents in the embryo axis and cotyledon was
      established. The ratios 4C/2C and (Sigma>2C)/2C were calculated. Dried seeds were
      subjected to laboratory germination tests following international seed testing
      association (ISTA) rules. Additionally, the absolute nuclear DNA content was
      estimated in the leaves of the studied species. During seed development nuclei
      with DNA contents from 2C to 128C were detected; the endopolyploidy pattern
      depended on the species, seed organ and developmental stage. The cell
      cycle/endoreduplication parameters correlated negatively with genome size. The
      (Sigma>2C)/2C ratio in the cotyledons reflected the seed developmental stage and
      corresponded with seed germinability. Therefore, this ratio is recommended as a
      marker in polysomatic seed research and production instead of the 4C/2C ratio,
      which does not consider the occurrence of endopolyploid cells.

PMID- 23136067
TI  - Functional characterization of SAG/RBX2/ROC2/RNF7, an antioxidant protein and an
      E3 ubiquitin ligase.
AB  - SAG (Sensitive to Apoptosis Gene), also known as RBX2 (RING box protein 2), ROC2
      (Regulator of Cullins 2), or RNF7 (RING Finger Protein 7), was originally cloned
      in our laboratory as a redox inducible antioxidant protein and later
      characterized as the second member of the RBX/ROC RING component of the SCF (SKP1
      CUL-F-box Proteins) E3 ubiquitin ligase. When acting alone, SAG scavenges oxygen
      radicals by forming inter- and intra-molecular disulfide bonds, whereas by
      forming a complex with other components of the SCF E3 ligase, SAG promotes
      ubiquitination and degradation of a number of protein substrates, including c
      JUN, DEPTOR, HIF-1alpha, IkappaBalpha, NF1, NOXA, p27, and procaspase-3, thus
      regulating various signaling pathways and biological processes. Specifically, SAG
      protects cells from apoptosis, confers radioresistance, and plays an essential
      and non-redundant role in mouse embryogenesis and vasculogenesis. Furthermore,
      stress-inducible SAG is overexpressed in a number of human cancers and SAG
      overexpression correlates with poor patient prognosis. Finally, SAG transgenic
      expression in epidermis causes an early stage inhibition, but later stage
      promotion, of skin tumorigenesis triggered by DMBA/TPA. Given its major role in
      promoting targeted degradation of tumor suppressive proteins, leading to
      apoptosis suppression and accelerated tumorigenesis, SAG E3 ligase appears to be
      an attractive anticancer target.

PMID- 23136069
TI  - Antinociceptive profile of potent opioid peptide AM94, a fluorinated analogue of
      biphalin with non-hydrazine linker.
AB  - AM94 is a fluorinated analog of biphalin with non-hydrazine linker that has an in
      vitro affinity for MU-opioid and delta-opioid receptors tenfold higher than
      biphalin. Furthermore, in vivo evaluation in rats showed that AM94 has in hot
      plate test - after both intracerebroventricular and intravenous administrations -
      a greater and more durable efficacy than biphalin. Here, the antinociceptive
      profile of AM94 is further evaluated by following two different administration
      routes, intrathecal and subcutaneous, and two different animal species, rats and
      mice. The analgesic potency of AM94 is compared with that of both the parent
      peptide biphalin and morphine. Results show that in rats (tail flick test) and in
      mice (formalin test), AM94 has a higher and more durable analgesic effect than
      biphalin after intrathecal and subcutaneous administrations. Conformational
      properties of biphalin and AM94 were also investigated by variable-temperature
      (1)H NMR and energy minimization.

PMID- 23136070
TI  - Correlation of the Kennedy Osteitis Score to clinico-histologic features of
      chronic rhinosinusitis.
AB  - BACKGROUND: Osteitis is a feature of chronic rhinosinusitis (CRS) and often
      associated with recalcitrant disease. Radiological characteristics of osteitic
      sinus changes are commonly reported in practice but the clinical and pathologic
      significance is poorly defined. The objective of this study was to correlate the
      Kennedy Osteitis Score (KOS) to clinico-histologic features of CRS. METHODS: A
      cross-sectional study of CRS patients undergoing sinus surgery was conducted.
      Osteitis was scored radiologically using the KOS. Associations between osteitis
      and histopathology, symptoms, 22-item Sino-Nasal Outcomes Test (SNOT-22),
      endoscopy, computed tomography (CT) mucosal score, and seromarkers were assessed.
      Interobserver correlation coefficient was performed. Additionally, the KOS was
      correlated to an alternate Global Osteitis Score. RESULTS: A total of 88 patients
      were assessed (45.5% female, age 50.3 +/- 13.6 years); 45 (51.1%) patients had
      osteitis. Patients with KOS >0, had greater endoscopy score (6.1 +/- 2.9 vs 4.4
      +/- 3.6, p = 0.03) and CT score (14.0 +/- 6.0 vs 10.1 +/- 5.7, p < 0.01) than
      those without osteitis. There was no difference in symptom score (2.4 +/- 1.3 vs
      2.4 +/- 1.1, p = 0.89) and SNOT-22 (2.0 +/- 1.0 vs 1.9 +/- 1.1, p = 0.56) in
      patients with and without osteitis. KOS was higher in patients with tissue
      eosinophilia >10/high-power field (HPF) (median 3.0 [IQR, 1.0-5.3] vs 0.0 [0.0
      4.0], p = 0.03) and serum eosinophilia >0.3 * 10(9) /L (4.0 [2.0-7.0] vs 1.0 [0.0
      4.0], p < 0.01). Importantly, this was also true for those without prior surgery.
      The interobserver correlation coefficient was good (R = 0.86, p < 0.001). There
      was a significant correlation between the KOS and the Global Osteitis Score (R =
      0.93, p < 0.001). CONCLUSION: The KOS is a simple, easy, and reproducible scale
      in assessing osteitic bones in patients with CRS and can predict measures of
      severity in eosinophilic rhinosinusitis.

PMID- 23136071
TI  - Influence of global climate change on chemical fate and bioaccumulation: the role
      of multimedia models.
AB  - Multimedia environmental fate models are valuable tools for investigating
      potential changes associated with global climate change, particularly because
      thermodynamic forcing on partitioning behavior as well as diffusive and
      nondiffusive exchange processes are implicitly considered. Similarly, food-web
      bioaccumulation models are capable of integrating the net effect of changes
      associated with factors such as temperature, growth rates, feeding preferences,
      and partitioning behavior on bioaccumulation potential. For the climate change
      scenarios considered in the present study, such tools indicate that alterations
      to exposure concentrations are typically within a factor of 2 of the baseline
      output. Based on an appreciation for the uncertainty in model parameters and
      baseline output, the authors recommend caution when interpreting or speculating
      on the relative importance of global climate change with respect to how changes
      caused by it will influence chemical fate and bioavailability.

PMID- 23136072
TI  - IR-monitored photolysis of CO-inhibited nitrogenase: a major EPR-silent species
      with coupled terminal CO ligands.
AB  - Fourier transform infrared spectroscopy (FTIR) was used to observe the photolysis
      and recombination of a new EPR-silent CO-inhibited form of alpha-H195Q
      nitrogenase from Azotobacter vinelandii. Photolysis at 4 K reveals a strong
      negative IR difference band at nu = 1938 cm(-1), along with a weaker negative
      feature at 1911 cm(-1). These bands and the associated chemical species have both
      been assigned the label "Hi-3". A positive band at nu = 1921 cm(-1) was assigned
      to the "Lo-3" photoproduct. By using an isotopic mixture of (12)C (16)O and (13)C
      (18)O, we show that the Hi-3 bands arise from coupling of two similar CO
      oscillators with one uncoupled frequency at approximately nu = 1917 cm(-1).
      Although in previous studies Lo-3 was not observed to recombine, by extending the
      observation range to 200-240 K, we found that recombination to Hi-3 does indeed
      occur, with an activation energy of approximately 6.5 kJ mol(-1). The frequencies
      of the Hi-3 bands suggest terminal CO ligation. This hypothesis was tested with
      DFT calculations on models with terminal CO ligands on Fe2 and Fe6 of the FeMo
      cofactor. An S = 0 model with both CO ligands in exo positions predicts symmetric
      and asymmetric stretches at nu = 1938 and 1909 cm(-1), respectively, with
      relative band intensities of about 3.5:1, which is in good agreement with
      experiment. From the observed IR intensities, Hi-3 was found to be present at a
      concentration about equal to that of the EPR-active Hi-1 species. The relevance
      of Hi-3 to the nitrogenase catalytic mechanism and its recently discovered
      Fischer-Tropsch chemistry is discussed.

PMID- 23136073
TI  - Organometallic hexahapto functionalization of single layer graphene as a route to
      high mobility graphene devices.

PMID- 23136074
TI  - Molecular pathogenesis of infections caused by Moraxella catarrhalis in children.
AB  - Moraxella catarrhalis (M. catarrhalis) is a human-restricted commensal of the
      normal bacterial flora in the upper respiratory tract of children, and - during
      the previous two decades - has been recognised as a true human pathogen. M.
      catarrhalis is the third most common pathogen causing acute otitis media in
      children, which is the most common reason to visit a paediatrician during
      childhood. Acute otitis media thus causes a high clinical and economical burden.
      With the introduction of the conjugate pneumococcal vaccines the microbiomic
      pattern in the nasopharyngeal flora of children has changed, and the frequency of
      isolation of M. catarrhalis has increased. Compared to adults, children are more
      often colonised with M. catarrhalis. Over the last three decades there has been a
      dramatic increase in the acquisition of beta-lactam resistance in M. catarrhalis.
      Today 95-100% of clinically isolated M. catarrhalis produce beta-lactamase. It is
      thus desirable to reduce the burden of M. catarrhalis disease by developing a
      vaccine. There are several potential vaccine antigen candidates in different
      stages of development, but none of them has entered clinical trials at the
      present time.

PMID- 23136076
TI  - From osmium hydrido vinylidene to osmacycles: the key role of osmabutadiene
      intermediates.
AB  - Osmium hydrido vinylidene 1 shows diverse cyclization reactivity with activated
      terminal alkynes. Treatment of 1 with HC=CCOR' (R'=OEt and Me) gave osmafurans 3a
      and 3b via osmium alkenyl/vinylidenes 2a and 2b. In addition, 1 reacted with
      HC=CCH(OH)C=CH to yield osmabenzene 4, in which the alkynol acted as a C(5)
      fragment to cyclize with 1. Mechanistic analysis indicates that these reactions
      and the previous formal [3+3] cycloadditions between 1 and HC=CCH(OH)R (R=Ph, Et,
      and vinyl) or HC=CCH(OEt)(2) all go through similar osmabutadiene intermediates.
      Subsequently, the intermediates either took a "coordination and cyclization"
      process or a "carbon-carbon coupling" path to cyclization, depending on the
      coordination ability of substituents on the terminal alkenyl carbon atom.

PMID- 23136075
TI  - Altered local and systemic immune profiles underlie lymph node metastasis in
      breast cancer patients.
AB  - Cancer-mediated immune dysfunction contributes to tumor progression and
      correlates with patient outcome. Metastasis to tumor draining lymph nodes (TDLNs)
      is an important step in breast cancer progression and is used to predict patient
      outcome and survival. Although lymph nodes are important immune organs, the role
      of immune cells in TDLNs has not been thoroughly investigated. We hypothesized
      that the host immune response in node negative (NN) patients is more intact and
      thereby can resist tumor invasion compared to node positive (NP) patients. As
      such, lymph node metastasis requires breakdown of the host immune response in
      addition to escape of cancer cells from the tumor. To investigate the
      immunological differences between NN and NP breast cancer patients, we purified
      and profiled immune cells from the three major compartments where cancer and
      immune cells interact: tumor, TDLNs and peripheral blood. Significant down
      regulation of genes associated with immune-related pathways and up-regulation of
      genes associated with tumor-promoting pathways was consistently observed in NP
      patients' TDLNs compared to NN patients. Importantly, these signatures were seen
      even in NP patients' tumor-free TDLNs, suggesting that such immune changes are
      not driven solely by local tumor invasion. Furthermore, similar patterns were
      also observed in NP patients' tumor and blood immune cells, suggesting that
      immunological differences between NN and NP patients are systemic. Together,
      these findings suggest that alterations in overall immune function may underlie
      risk for LN metastasis in breast cancer patients.

PMID- 23136077
TI  - Using thermally regenerable cerium oxide nanoparticles in biocomputing to perform
      label-free, resettable, and colorimetric logic operations.
AB  - A label-free, resettable, and colorimetric logic network has been realized by
      utilizing thermally regenerable cerium oxide nanoparticles and biocatalytic
      reactions. Coupling switchable CeO(2)  nanoparticles with biocomputing would
      convert molecular recognition events into colorimetric outputs and make logic
      gates feasible to reset.

PMID- 23136078
TI  - Qualitative exploration of sexual health in old age.

PMID- 23136079
TI  - HIV testing for acute medical admissions: evaluation of a pilot study in
      Leicester, England.
AB  - OBJECTIVES: The 2008 UK National Guidelines for HIV testing recommended HIV
      testing should be offered to all general medical admissions aged 16-60 years in
      high prevalence areas, and that this should be evaluated to ensure this was
      effective in diagnosing previously undiagnosed HIV. METHODS: HIV testing was
      introduced as a routine test for all patients admitted to the acute medical
      admissions unit, comparisons were made between the testing rates before, during
      and after this intervention. RESULTS: The pilot was initiated in August 2009.
      Prior to the pilot the unit was carrying out 15 tests per month. However, when
      the pilot was introduced 82 tests were being carried out per month with a total
      of 10 new diagnoses since the start of the pilot. The proportion of patients
      tested versus those eligible for testing remained low varying between 6% and 22%
      month by month. 10 patients we found to be HIV positive with a prevalence of
      approximately 1%, 10 fold higher than the cut off for cost effectiveness used in
      the guidelines. CONCLUSIONS: Overall the pilot showed that HIV testing could be
      delivered without the use of extra resources and is acceptable to patients.

PMID- 23136080
TI  - Review of genital biopsies in a genitourinary medicine clinic: are they
      necessary?

PMID- 23136081
TI  - Kinetic analysis of intracellular Hoechst 33342--DNA interactions by flow
      cytometry: misinterpretation of side population status?
AB  - We outline a simple approach involving instrument setup and calibration for the
      analysis of Hoechst dye 33342-loading in human cell lines for exploring
      heterogeneity in dye efflux efficiency and the status of side population (SP)
      A549 lung cancer cells. Dual excitation 488 nm/multiline UV (351-364 nm) flow
      cytometry was used to confirm ABCG2-specific inhibition of dye efflux using
      Fumitremorgin C. Transporter gene expression, assayed by qRT-PCR, confirmed
      higher expression of ABCG2 versus ABCB1, reiterated in a cloned subline.
      Coexpression of aldehyde dehydrogenase genes ranked as aldehyde dehydrogenase
      class 1A1 (ALDH1A1) > ALDH3A1 > ALDH3, relative expression of all genes was again
      reiterated in a cloned subline. Permeabilized cells were used to create
      red:violet (660:405 nm Em wavelengths) ratiometric references for mapping
      temporal changes in Hoechst 33342-DNA fluorescence in live cells. A live cell
      "kinetic SP gate" tracked progressive dye loading of the whole population and
      coapplication of the far red (>695 nm wavelength) fluorescing dye DRAQ7 enabled
      viable cell gating. Kinetic gating revealed a continuum for dye accumulation
      suggesting that SP enumeration is critically dependent upon the nonlinear
      relationship of the spectral shift with progressive dye-DNA binding and thus
      requires accurate definition. To this end, permeabilized cell reference samples
      permit reproducible instrument setup, guide gate boundaries for SP and
      compromised cells, and offer a simple means of comparing SP enumeration across
      laboratory sites/platforms. Our approach reports the dynamic range for the
      spectral shift, revealing noninformative staining conditions and explaining a
      source of variability for SP enumeration. We suggest that live cell kinetic
      sorting of all cells with the same dye:DNA load but with differences in efflux
      capacity can be used to explore drug resistance capability without prejudice. The
      SP phenotype should be regarded as a kinetic parameter and not a fixed
      characteristic--critical for functional assay design and the interpretation of
      heterogeneity.

PMID- 23136082
TI  - Gene expression differences in nitric oxide and reactive oxygen species
      regulation point to an altered innate immune response in chronic rhinosinusitis.
AB  - BACKGROUND: The complex interplay between host, environment, and microbe in the
      etiopathogenesis of chronic rhinosinusitis (CRS) remains unclear. This study
      focuses on the host-microbe interaction, specifically the regulation of nitric
      oxide (NO) and reactive oxygen species (ROS) against the pathogenic organism
      Staphylococcus aureus (S. aureus). NO and ROS play crucial roles in innate
      immunity and in the first-line defense against microbial invasion. METHODS:
      Sinonasal tissue samples were harvested from CRS and control patients during
      surgery. CRS patients were classified S. aureus biofilm-positive (B+) or biofilm
      negative (B-) using fluorescence in situ hybridization and clinically as polyp
      positive (P+) or polyp-negative (P-). Samples were assessed using an NO
      polymerase chain reaction (PCR) array containing 84 genes involved in NO and ROS
      regulation, and gene expression of all subgroups were compared to each other.
      RESULTS: Twenty-three samples were analyzed with 31 genes significantly changed,
      the greatest seen in the B+P+ CRS patients. Four genes consistently displayed
      differential expression between the groups including the cytoprotective oxidation
      resistance 1 (OXR1) and peroxiredoxin 6 (PRDX6), neutrophil cytosolic factor 2
      (NCF2), and the prion protein (PRNP) genes. CONCLUSION: Alteration in gene
      expression points to impaired innate immune responses differing among CRS
      subgroups based on S. aureus biofilm and polyp status. The consistent alteration
      of 4 genes among distinct groups demonstrates that S. aureus biofilms and polyps
      are associated with specific changes in gene expression. Further studies are
      required to validate these findings in a wider cohort of patients and correlate
      this to protein expression and disease manifestation.

PMID- 23136083
TI  - Efficient nonviral gene therapy with FasL and Del1 fragments in mice.
AB  - BACKGROUND: The expression of FasL in cancer cells is currently being explored as
      a potential cancer therapy. Because high levels of FasL are necessary for
      effective treatment, current methods typically rely on the use of highly
      efficient viral vectors. However, because viral vector-based gene therapy is
      associated with certain risks, the development of effective nonviral routes for
      gene delivery would be useful. The present study aimed to improve FasL gene
      therapy with a nonviral vector by taking advantage of the E3 and C1 domains of
      Del1 protein, which induces apoptosis and localizes to the extracellular matrix.
      METHODS: Mouse explanted tumors derived from a human oral squamous cell carcinoma
      cell line, SCCKN, were treated with plasmids encoding FasL (pFasL), E3C1 (pE3C1),
      and a fusion of FasL and E3C1 (pFasL-E3C1). The plasmids were injected locally
      every 7 days along with a transfection reagent, Jet-PEI (PolyPlus-transfection,
      San Marcos, CA, USA). RESULTS: All mice treated with a negative control plasmid
      or pFasL died within 49 days. By contrast, 83% of mice treated with pFasL-E3C1
      survived longer than 49 days. Histochemical studies revealed that the fusion
      protein is localized to the stroma and induces apoptosis in stromal cells and
      adjacent parenchymal cells. CONCLUSIONS: The results obtained in the present
      study suggest that the protein deposition-based approach described, which makes
      use of the E3 and C1 domains of Del1, could comprise a novel method for cancer
      gene therapy with nonviral vectors.

PMID- 23136087
TI  - Tumor suppressor TSLC1 is implicated in cell proliferation, invasion and
      apoptosis in laryngeal squamous cell carcinoma by regulating Akt signaling
      pathway.
AB  - Overwhelming evidence has demonstrated that TSLC1 (tumor suppressor in lung
      cancer 1), a novel tumor suppressor, is crucially implicated in various
      biological processes including progression, proliferation and apoptosis during
      tumorigenesis. However, the exact functions and molecular details of TSLC1 in
      laryngeal cancer remain ill-defined. Here, the expression of TSLC1 in laryngeal
      squamous cell carcinoma (LSCC) tissues and cells was detected, and the biological
      roles of TSLC1 in LSCC cells were investigated. The results showed that
      expressions of TSLC1 mRNA and protein were significantly reduced in LSCC tissues
      with low expression in 18 of 85 (21.18 %) and 16 of 85 (18.82 %), respectively.
      Additionally, statistical analysis revealed a significant correlation of TSLC1
      expression with TNM staging and lymph node metastases (P < 0.05), but not related
      to age, gender and tumor differentiation (P > 0.05). Elevation of TSLC1 level
      inhibited cell proliferation, reduced cell invasion in vitro and induced cell
      apoptosis in Hep-2 cells, most importantly, TSLC1 upregulation decreased the
      level of pAkt, but not changed the level of total Akt in Hep-2 cells. Stepwise
      investigations demonstrated that overexpression of TSLC1 in Hep-2 cells increased
      caspase-3 activity and expressions of bax and p21 proteins but decreased the
      levels of bcl-2, MMP-2 and MMP-9 proteins. These data suggest that TSLC1 may
      exert essential roles in the progression and development of LSCC, and thus TSLC1
      may be a potential molecular target for LSCC treatment.

PMID- 23136088
TI  - Effects of Astragalus membranaceus with supplemental calcium on bone mineral
      density and bone metabolism in calcium-deficient ovariectomized rats.
AB  - It has been reported that Astragalus membranaceus, an Asian traditional herb, has
      an estrogenic effect in vitro. To examine the possible role of A. membranaceus
      extract with supplemental calcium (Ca) on bone status in calcium-deficient (LCa)
      ovariectomized (OVX) rats, a total of 48 female rats were divided into six
      groups: (1) normal control, (2) sham operation with LCa (sham-LCa), (3) OVX with
      LCa (OVX-LCa), (4) A. membranaceus supplementation with OVX-LCa (OVX-MLCa), (5)
      Ca supplementation with OVX (OVX-Ca), and (6) A. membranaceus and Ca
      supplementation with OVX (OVX-MCa). A. membranaceus ethanol extract (500 mg/kg
      BW) and/or Ca (800 mg/kg BW) were administered orally for 8 weeks along with a Ca
      deficient diet. Results revealed that Ca supplementation with or without A.
      membranaceus extract significantly improved bone mineral density, biomechanical
      strength, and ash weight of the femur and tibia in OVX rats. High Ca with A.
      membranaceus combination supplementation significantly increased the ash weight
      of the femur and tibia and decreased urinary Ca excretion compared with
      supplementation of Ca alone. Uterine weight was not changed by A. membranaceus
      administration in OVX rats. These results suggest that A. membranaceus extract
      combined with supplemental Ca may be more protective against the Ca loss of bone
      than A. membranaceus or supplementation of Ca alone in calcium-insufficient
      postmenopausal women.

PMID- 23136089
TI  - Spontaneous emission and nonlinear response enhancement by silver nanoparticles
      in a Nd3+-doped periodically poled LiNbO3 laser crystal.

PMID- 23136090
TI  - Chiral supramolecular switches based on (R)-binaphthalene-bipyridinium guests and
      cucurbituril hosts.
AB  - We designed and synthesized the three molecular tweezers 1 a-c(4+) containing an
      electron acceptor 4,4'-bipyridinium (BPY(2+)) unit in each of the two arms and an
      (R)-2,2'-dioxy-1,1'-binaphthyl (BIN) unit that plays the role of chiral centre
      and the hinge of the structure. Each BPY(2+) unit is connected to the BIN hinge
      by an alkyl chain formed by two- (1 a(4+)), four- (1 b(4+)), or six-CH(2) (1
      c(4+)) groups. The behavior of 1 a-c(4+) upon chemical or photochemical reduction
      in the absence and in the presence of cucurbit[8]uril (CB[8]) or cucurbit[7]uril
      (CB[7]) as macrocyclic hosts for the bipyridinium units has been studied in
      aqueous solution. A detailed analysis of the UV/Vis absorption and circular
      dichroism (CD) spectra shows that the helicity of the BIN unit can be reversibly
      modulated by reduction of the BPY(2+) units, or by association with
      cucurbiturils. Upon reduction of 1 a-c(4+) compounds, the formed BPY(+.) units
      undergo intramolecular dimerization with a concomitant change in the BIN dihedral
      angle, which depends on the length of the alkyl spacers. The alkyl linkers also
      play an important role in association to cucurbiturils. Compound 1 a(4+), because
      of its short carbon chain, associates to the bulky CB[8] in a 1:1 ratio, whereas
      in the case of the smaller host compound CB[7] a 1:2 complex is obtained.
      Compounds 1 b(4+) and 1 c(4+), which have longer linkers, associate to two
      cucurbiturils regardless of their sizes. In all cases, association with CB[8]
      causes an increase of the BIN dihedral angle, whereas the formation of CB[7]
      complexes causes an angle decrease. Reduction of the CB[8] complexes results in
      an enhancement of the BPY(+.) dimerization with respect to free 1 a-c(4+) and
      causes a noticeable decrease of the BIN dihedral angle, because the BPY(+.) units
      of the two arms have to enter into the same macrocycle. The dimer formation in
      the CB[8] complexes characterized by a 1:2 ratio implies the release of one
      macrocycle showing that the binding stoichiometry of these host-guest complexes
      can be switched from 1:2 to 1:1 by changing the redox state of the guest. When
      the reduction is performed on the CB[7] complexes, dimer formation is totally
      inhibited, as expected because the CB[7] cavity cannot host two BPY(+.) units.

PMID- 23136091
TI  - Photo Quiz. A man with fever and deranged liver function.

PMID- 23136093
TI  - Crossing borders. Viral hepatitis in the United States, Mexico, and the United
      States-Mexico border region.

PMID- 23136095
TI  - Isolation of erythrocytes infected with viable early stages of Plasmodium
      falciparum by flow cytometry.
AB  - The erythrocytic life cycle of Plasmodium falciparum is highly associated with
      severe clinical symptoms of malaria that causes hundreds of thousands of death
      each year. The parasite develops within human erythrocytes leading to the
      disruption of the infected red blood cell (iRBC) prior to the start of a new
      cycle of erythrocyte infection. Emerging mechanisms of resistance against
      antimalarial drugs require improved knowledge about parasite's blood stages to
      facilitate new alternative antimalarial strategies. For the analysis of young
      blood stages of Plasmodium at the molecular level, the isolation of ring stages
      is essential. However, early stages can hardly be separated from both, late
      stages and non-infected red blood cells using conventional methods. Here, iRBCs
      were stained with the DNA-binding dyes Vybrant(r) DyeCycleTM Violet and SYBR(r)
      Green I. Subsequently, cells were subjected to flow-cytometric analysis. This
      enabled the discrimination of early stage iRBCs as well as late-stage iRBCs from
      non-infected erythrocytes and the properties of the used dyes were evaluated.
      Moreover, early stage iRBCs were isolated with high purity (>98%) by FACS.
      Subsequently, development of sorted early stages of the parasite was monitored
      over time and compared with control cultures. The described flow cytometry
      method, based on staining with Vybrant DyeCycle Violet, allows the isolation of
      viable ring stages of the malarial agent P. falciparum, and thereby provides the
      basis for new, broad-range molecular investigations of the parasite.

PMID- 23136096
TI  - Highly efficient ultrafast electron injection from the singlet MLCT excited state
      of copper(I) diimine complexes to TiO2 nanoparticles.

PMID- 23136097
TI  - A simple route to hierarchically assembled micelles and inorganic nanoparticles.
AB  - Earning their stripes: A hierarchical assembly of micelles composed of an
      amphiphilic diblock copolymer, poly(styrene)-block-poly(4-vinylpyridine) (PS-b
      P4VP), were made by combining controlled evaporative self-assembly of the
      confined PS-b-P4VP toluene solution in a cylinder-on-Si geometry with spontaneous
      self-assembly of micelles. This method gave microscopic stripes of nanometer
      sized PS-b-P4VP micelles within the stripes (see pictures).

PMID- 23136098
TI  - [Surgery of high-grade asymptomatic stenosis of the internal carotid artery].
AB  - OBJECTIVE: Surgery of carotid artery stenosis is an evidence-based procedure. In
      Germany approximately 25 percent of the strokes are caused by arteriosclerotic
      processes in the extracranial internal carotid artery and are consequently
      potentially avoidable by an appropriate treatment. The symptoms, the stenosis
      degree as well as the perioperative risk represent the basis for the indication.
      The perioperative complication rate should be under 3 percent for those cases
      with asymptomatic stenoses and under 6 percent for those with symptomatic
      stenoses. INDICATION: The most frequently applied operation procedures comprise
      carotid thrombo-endarterectomy (TEA) including patch graft and the eversion
      endarterectomy. In the following video we present both methods in a 76-year-old
      female patient with an asymptomatic 95 percent stenosis as well as in an 84-year
      old female patient with an asymptomatic 85 percent stenosis operated under
      regional anaesthesia. METHOD: Regional anaesthesia is performed through
      installation of a high cervical block under reclination of the head to the
      contralateral side. Then incision of the skin and the platysma along the front of
      the sternocleidomastoid muscle. Preparation of the carotid bifurcation with
      minimal manipulation as well as protection of the surrounding neural structures.
      Afterwards clamping of the vessels under permanent neurological monitoring and
      controlled hypertonia. Open thrombo-endarterectomy after longitudinal arterial
      incision with plaque removal en bloc and closure by using a bovine patch graft in
      four-point seam technique. This method should be preferred in cases with long
      segment stenosis as well as in cases with a small lumen internal carotid artery.
      In the framework of eversion endarterectomy, we perform a tangential resection of
      the ACI on the bifurcation. The plaque cylinder is mobilised afterwards and is
      removed through eversion of the whole vessel. Then the reinsertion of the ACI in
      the bifurcation can be performed with an additional shortening of the artery in
      cases of kinking. In this way short- segment stenosis lend themselves to fast and
      safe treatment. In all cases digital subtraction angiography is recommended by
      the authors for intraoperative quality monitoring. CONCLUSION: In the hands of
      experienced vascular surgeons, the open carotid TEA including patch graft and the
      eversion endarterectomy under regional anaesthesia represent highly effective
      procedures for symptomatic/asymptomatic carotid stenosis. The S3-guidelines for
      the therapy of carotid artery stenosis will be published this year and should be
      consulted for the interdisciplinary therapy decision.

PMID- 23136099
TI  - Hybrid operation for a thoracoabdominal aortic aneurysm.
AB  - OBJECTIVE: The treatment of thoracoabdominal aortic aneurysms remains an ongoing
      challenge in vascular surgery and has been associated with high periprocedural
      mortality. Since the introduction of endovascular procedures in the treatment of
      aortic pathologies during the last decade, new therapeutic options have arisen.
      We report here some technical aspects of a 2-step hybrid-procedure that consists
      of an initial debranching of all visceral arteries by perfusing them through a
      special vascular prosthesis, which is anastomosed to the healthy common iliac
      artery. The second step is performed after recovery of the patient from the
      debranching procedure and stentgraft prostheses are implanted to fully exclude
      the aneurysm. INDICATIONS: Thoracoabdominal aortic aneurysm. PROCEDURE: Two-step
      hybrid-procedure for treatment of thoracoabdominal aneurysms. CONCLUSION: In our
      opinion, this procedure is, although technically demanding, safely performable
      with a tolerable periprocedural morbidity and mortality. Major advantages are the
      restriction to one visceral cavity and a sequential debranching that allows us to
      avoid use of a temporary bypass. This procedure appears to be a promising
      alternative to conventional thoracoabdominal aortic repair in centres with
      expertise in visceral artery revascularisation.

PMID- 23136100
TI  - [Vascular medicine = angiology, vascular surgery, radiology].

PMID- 23136101
TI  - [Aortic aneurysm 2012: open, hybrid or total endovascular repair?].
AB  - During the past two decades, minimally invasive endovascular procedures have
      changed therapeutic strategies. Such techniques have now become the method of
      choice for practically all vascular and aortic pathologies. This development is
      especially apparent in the treatment of aortic aneurysms. The purpose of this
      report is to provide a critical review about the current standard of care of
      abdominal and thoracic aorta based on an electronic Medline literature search.
      For elective infrarenal aneurysms, endovascular aneurysm repair (EVAR) has become
      a widely accepted alternative to open repair in cases with appropriate
      morphology. Currently, fenestrated (FEVAR) or branched endografts offer promising
      short- and mid-term results in juxtarenal aneurysms, however, these techniques
      are complex, technically challenging, and expensive. The alternative chimney or
      sandwich graft technique are becoming more common because they are feasible using
      standard endografts. Thoracic endovascular aortic repair (TEVAR) is already the
      gold standard for some descending pathologies. Complex thoracoabdominal aneurysms
      still require open surgery in centres of excellence, whereby, total endovascular
      repair or hybrid procedures have proved to be feasible in such specialist centres
      for selected patients.

PMID- 23136102
TI  - [Antithrombotic therapy after peripheral vascular treatment: what is evidence
      based?].
AB  - Peripheral arterial occlusive disease is one manifestation of the systemic
      disease atherosclerosis. The initial therapy for every arteriosclerotic disease
      is aimed at reducing cardiovascular risk factors by lifestyle modification and
      medication. Patients who require surgical revascularisation need long-term
      antiplatelet therapy or anticoagulation. This therapy has to be differentiated
      according to the vascular territory involved and the method used for
      revascularisation. After local thrombendarterectomy, alloplastic bypass graft
      surgery of the aortic, aorto-iliac, aorto-femoral or femoro-popliteal region
      above the knee, long-term ASA 100 mg/d or clopidogrel 75 mg/d should be
      initiated. After alloplastic bypass grafting below the knee the combination of
      ASA 100 mg/d and clopidogrel 75 mg/d should be used. In contrast, after venous
      grafts the patency rate is improved by anticoagulation with vitamin K antagonists
      (INR 2-3), if there is a low risk of bleeding. If there is a contraindication to
      vitamin K antagonists, ASA 100 mg/d should be used. After revascularisation, a
      structured surveillance programme should be implemented aiming at controlling
      cardiovascular risk factors and monitoring the vascular state, as well as the
      anticoagulation and the antiplatelet therapy.

PMID- 23136103
TI  - [Aneurysms of the deep femoral artery: a systematic review of literature].
AB  - INTRODUCTION: True aneurysms of the deep femoral artery (APFA) are rare and are
      usually presented as case reports. Recommendations for diagnostics and therapy of
      APFAs are based on low-level evidence only. The purpose of this paper was to
      summarise the existing world experience with APFA. MATERIAL/METHODS: On the
      occasion of our own case a systematic review of the literature was performed for
      diagnostics and therapy for true APFA. Publications retrieved from PubMed,
      EMBASE, and the Cochrane Collaboration as well as by hand search from their
      references were reviewed. RESULTS: From 2002 onwards 25 papers on true APFAs were
      published in the English and German literature. Apart from two retrospective
      studies over a longer period of time these were exclusively case reports. A total
      of 55 true APFAs were reported in 47 patients with a mean age of 63 years.
      Therapeutic intervention was due to a rupture in 10 cases (18 %). The mean
      maximal diameter of APFA at presentation was 5.4 cm (2-18 cm). APFAs that were
      not ruptured presented frequently as a painful pulsatile mass in the groin and
      thigh. Therapeutic options for APFA included, apart from surgical resection with
      or without reconstruction of the deep femoral artery, the endovascular repair.
      DISCUSSION: Symptoms of swelling and pain in the presence of a mass at the
      proximal thigh should raise the suspicion of an APFA. Surgical therapy should be
      performed electively in APFAs with a diameter of more than 2 cm or in cases of
      rapid progression as well as in all symptomatic or ruptured cases. The
      endovascular approach should be considered as an alternative option in all cases.

PMID- 23136104
TI  - [The economic solution for integrating radiology and surgery: hybrid OR].
AB  - Currently, interventional (angiographically-guided) therapies have become more
      and more important in cardiovascular medicine. Hybrid procedures in hybrid
      operating rooms (ORs) have now become major topics at national and international
      meetings. A few hospitals have already implemented the project "hybrid OR", in
      some institutions the system is still in the planning stage. The aim of our
      article is to present the hospital management point of view, and thus, to focus
      on the economic and logistic issues from planning through to implementation.

PMID- 23136105
TI  - [Immunoadsorption in thrombangiitis obliterans: a promising therapeutic option:
      results of a consecutive patient cohort treated in clinical routine care].
AB  - BACKGROUND: Thrombangiitis obliterans or Buerger's disease is a segmental
      inflammatory disease affecting small and medium-sized veins and arteries, which
      most often affects young smokers leading to thrombophlebitis and acral ischaemic
      syndromes, inducing high amputation rates. Based on positive results of a former
      pilot study we report on our results of immunoadsorption (IA) in clinical routine
      care, where IA was offered as a treatment option. PATIENTS AND METHODS: The
      uncontrolled course of 12 consecutive TAO-patients treated by IA on a series of 5
      consecutive days was observed. Follow-up period was 14.1 (ranging from 1-26)
      months. RESULTS: Eight patients were treated with one, four patients completed 2
      IA-series. In 9 patients an early onset and lasting clinical improvement and an
      improvement of ischaemia was noted. The intake of pain-relievers (especially
      opioids) sank drastically. Eight patients returned to work. Retrospectively, in
      two out of three treatment failures the correct diagnosis of TAO was
      questionable. CONCLUSION: IA seems to be a promising treatment option for
      patients suffering from TAO which should be further evaluated in controlled
      clinical trials.

PMID- 23136106
TI  - [Segmental arterial mediolysis: pathogenesis of aneurysms and dissections in
      patients younger than 60 years].
AB  - BACKGROUND: Complications deriving from arterial aneurysm and dissection without
      signs of atherosclerosis are rare clinical entities. In recent literature case
      reports show a descriptive similarity of pathological findings summarized as
      segmental arterial mediolysis (SAM). OBJECTIVE: The purpose of this study was to
      answer the question whether, among 16 patients suffering from SAM histological
      findings corresponded and assess causality. MATERIALS AND METHODS: In a
      prospective prognostic trial sixteen patients were enrolled between 1st January
      2008 and 31st October 2011. Inclusion criteria were a lack of atherosclerosis,
      age under 60 and clinical findings. Most of these sixteen patients were treated
      as emergency cases of life-threatening blood loss or organ system ischemia.
      Thirteen of the patients were male, 3 female and their average age was 44 (28-59)
      years. Localisation of the segmental aneurysm or dissection showed a broad
      variability from central to renovisceral and peripheral lesions. Imaging
      diagnostics (e.g., US and CT-A) were complemented by exclusion of positive family
      history, connective tissue diseases and autoimmune or inflammative disorders. In
      8 patients with open vascular reconstructions, it was possible to obtain a biopsy
      from the target lesion to analyse morphological and immunochemical expression
      levels (e.g., MMP1-12, vWF, vSMC or CD 68). RESULTS: None of the patients died
      nor had described familiar associations. Even the examination of twins with sCAD
      showed no coincidence. Differential diagnostic findings were excluded. All
      patients agreed to undergo human genetic screening. The 8 biopsy tissues showed
      homogeneously mediolysis with focal and increasingly confluent lesions. Main
      findings were that the vessel wall layering was destroyed and that
      capillarisation was initiated from the adventitial layer. Furthermore, all
      patients suffered from hypertension associated to the SAM, or developed it during
      surveillance. CONCLUSION: SAM is a rare, life-threatening diagnosis and has to be
      taken into consideration in young patients with aneurysm and dissection of
      unusual locations. Rare vascular diseases should have a forum in future
      investigations which might highlight molecular genetic triggers and associated
      diseases, e.g., hypertension and aortic type B dissection.

PMID- 23136107
TI  - [Venous aneurysm as a therapeutic problem: various management strategies in
      selected patients: our experience].
AB  - Venous system aneurysms appear relatively rarely, and are even more rarely
      diagnosed, especially if asymptomatic. In the material of our clinic we provide a
      variety of practices in three patients with venous aneurysms depending on the
      location, symptoms and main disease. In some patients the occurrence of pulmonary
      embolism is the first symptom of venous aneurysms, having influence on the
      selection of further diagnostics, conservative treatment, as well as on
      endovascular or operating procedure. The proper diagnosis of a venous aneurysm
      takes place in case of doubling or tripling of the diameter of the basic
      dimension of the lumen, often with the presence of thrombotic material.
      Asymptomatic venous aneurysms are usually detected during routine pre-operative
      diagnosis also including duplex-Doppler studies. In the presence of pulmonary
      embolism positive angio-CT and scintigraphy raise the suspicion of venous
      aneurysm unless any other reason is apparent. There is no standard treatment of
      venous aneurysms. This has to do with the relatively low epidemiology, diversity
      of location, difficulties in determining the proper primary and secondary
      aetiology, anatomy and coexisting diseases. Despite the many unknowns a few
      issues should be considered before appropriate treatment is undertaken.
      Undoubtedly, the shape itself, the location and size of the aneurysm with the
      presence or not of thrombotic material are of great value in evaluating the risk
      of complications, including possibly lethal pulmonary embolism, local symptoms of
      venous hypertension and possible complications of surgery. In this paper we
      present 3 patients treated for venous aneurysms located in different regions:
      popliteal vein, brachial vein and iliac internal vein.

PMID- 23136108
TI  - [Surgery meets nephrology: surgical indications for kidneys with renal artery
      occlusion: an interdisciplinary challenge].

PMID- 23136110
TI  - Noninvasive Staphylococcus aureus biofilm determination in chronic rhinosinusitis
      by detecting the exopolysaccharide matrix component poly-N-acetylglucosamine.
AB  - BACKGROUND: The role that bacterial biofilms might play in recalcitrant forms of
      chronic rhinosinusitis (CRS) is increasingly being recognized. However, the
      detection of bacteria existing in this form, using standard culture, is limited
      by their unique metabolically inactive properties. All current biofilm diagnostic
      modalities require invasive mucosal biopsies, which limit their use to the
      operating theatre. METHODS: Twenty CRS patients and 5 controls were enrolled in a
      prospective study to assess the feasibility of noninvasively diagnosing S. aureus
      biofilms by detecting the biofilm matrix polysaccharide poly-N-acetylglucosamine
      (PNAG). An immunofluorescence protocol was developed for PNAG detection and
      compared with both standard microbiological cultures and fluorescence in situ
      hybridization (FISH). RESULTS: Thirteen of 20 CRS patients had evidence of S.
      aureus biofilm formation using FISH. Of these, 12 had detectable PNAG.
      Interestingly none of the S. aureus FISH-negative patients were PNAG-positive
      despite the presence of coagulase-negative Staphylococci biofilms, some of which
      may exhibit PNAG in their pathogenic forms. The development of a noninvasive S.
      aureus biofilm diagnostic test provides a reliable means to identify a high-risk
      group of CRS patients who harbor S. aureus biofilms. The ability to be used
      outside of the perioperative period to assess surgical efficacy, guide
      management, and evaluate new treatment modalities provides a significant advance
      in this field of research and clinical practice. CONCLUSION: This study has
      confirmed the feasibility of noninvasive detection of S. aureus biofilms with a
      simple test that produces results comparable to the more invasive methods that
      are currently relied upon.

PMID- 23136111
TI  - High quantum efficiency in solution and vacuum processed blue phosphorescent
      organic light emitting diodes using a novel benzofuropyridine-based bipolar host
      material.
AB  - High quantum efficiency in solution and vacuum processed blue phosphorescent
      organic light emitting diodes are achieved using a new benzofuropyridine based
      bipolar host material. High quantum efficiencies of 18.0% and 23.0% are obtained
      in soluble and vacuum evaporable blue devices.

PMID- 23136112
TI  - Cloning and characterization of an mRNA encoding an insulin receptor from the
      horned scarab beetle Onthophagus nigriventris (Coleoptera: Scarabaeidae).
AB  - The insulin signaling pathway is the primary signaling pathway coupling growth
      with nutritional condition in all animals. Sensitivity to circulating levels of
      insulin has been shown to regulate the growth of specific traits in a dose
      dependent manner in response to environmental conditions in a diversity of insect
      species. Alternative phenotypes in insects manifest in a variety of morphologies
      such as the sexually dimorphic and male dimorphic horned beetles. Large males of
      the sexually dimorphic dung beetle Onthophagus nigriventris develop a thoracic
      horn up to twice the length of the body whereas small males and females never
      develop this horn. The regulation of this dimorphism is known to be nutrition
      dependent for males. We focused on the insulin signaling pathway as a potential
      regulator of this dimorphism. We sequenced a full-length gene transcript encoding
      the O. nigriventris insulin receptor (OnInR), which is the receptor for
      circulating insulin and insulin-like peptides in animals. We show that the
      predicted OnInR protein is similar in overall amino acid identity to other
      insulin receptors (InRs) and is most closely related phylogenetically to insect
      InRs. Expression of the OnInR transcript was found during development of imaginal
      tissues in both males and females. However, expression of OnInR in the region
      where a horn would grow of small males and female was significantly higher than
      in the horn tissues of large males at the end of growth. This variation in OnInR
      expression between sexes and morphs indicates a role for the InR in polymorphic
      horn development.

PMID- 23136113
TI  - Total synthesis of (-)-zampanolide and structure-activity relationship studies on
      (-)-dactylolide derivatives.
AB  - A new total synthesis of the marine macrolide (-)-zampanolide (1) and the
      structurally and stereochemically related non-natural levorotatory enantiomer of
      (+)-dactylolide (2), that is, ent-2, has been developed. The synthesis features a
      high-yielding, selective intramolecular Horner-Wadsworth-Emmons (HWE) reaction to
      close the 20-membered macrolactone ring of 1 and ent-2. The beta-keto
      phosphonate/aldehyde precursor for the ring-closure reaction was obtained by
      esterification of a omega-diethylphosphono carboxylic acid fragment and a
      secondary alcohol fragment incorporating the THP ring that is embedded in the
      macrocyclic core structure of 1 and ent-2. THP ring formation was accomplished
      through a segment coupling Prins-type cyclization. Employing the same overall
      strategy, 13-desmethylene-ent-2 as well as the monocyclic desTHP derivatives of 1
      and ent-2 were prepared. Synthetic 1 inhibited human cancer cell growth in vitro
      with nM IC(50) values, while ent-2, which lacks the diene-containing hemiaminal
      linked side chain of 1, is 25- to 260-fold less active. 13-Desmethylene-ent-2 as
      well as the reduced versions of ent-2 and 13-desmethylene-ent-2 all showed
      similar cellular activity as ent-2 itself. The same activity level was attained
      by the monocyclic desTHP derivative of 1. Oxidation of the aldehyde functionality
      of ent-2 gave a carboxylic acid that was converted into the corresponding N-hexyl
      amide. The latter showed only MUM antiproliferative activity, thus being several
      hundred-fold less potent than 1.

PMID- 23136114
TI  - Intermittent subcutaneous furosemide: parenteral diuretic rescue for hospice
      patients with congestive heart failure resistant to oral diuretic.
AB  - Patients with congestive heart failure (CHF) account for up to 12% of the hospice
      population and often experience significant symptoms related to volume overload.
      Diuretic therapy is the cornerstone of treatment but administration (PO) often
      becomes ineffective and (i.v., i.m.) routes cause discomfort or may not be
      feasible to ameliorate symptoms. Subcutaneous dosing of furosemide has been
      explored as a potential alternative for management of CHF symptoms. We report 2
      cases of CHF resistant to oral diuretic and examine the clinical utility of
      subcutaneous furosemide in an inpatient palliative care unit and a home hospice
      setting. Our case series supports the use of subcutaneous therapy as a potential
      alternative in palliative care and hospice patients.

PMID- 23136115
TI  - Desirable attributes of vaccines for deployment in low-resource settings.
AB  - A number of product development partnerships are actively developing new vaccines
      to combat infectious diseases in developing countries. To be effective, the
      products under development should not only be safe, efficacious, and affordable,
      but they should also have additional desirable technical attributes, including
      enhanced stability, efficient packaging, and improved ease of delivery. New
      technologies are now available to achieve these attributes; however, many of the
      technologies have yet to be adopted by the vaccine industry. This commentary
      discusses the opportunities and challenges associated with advancing such
      attributes, especially vaccine thermostability and dose sparing strategies, and
      the critical issues that must be addressed to bridge the gap between technology
      development and product development.

PMID- 23136116
TI  - Mycobacterium tuberculosis region of difference (RD) 2 antigen Rv1985c and RD11
      antigen Rv3425 have the promising potential to distinguish patients with active
      tuberculosis from M. bovis BCG-vaccinated individuals.
AB  - Antigens encoded in the region of difference (RD) of Mycobacterium tuberculosis
      constitute a potential source of specific immunodiagnostic antigens for
      distinguishing tuberculosis (TB) infection from BCG vaccination. We evaluated the
      diagnostic potential of specific T-cell epitopes selected from two immunodominant
      antigens, Rv1985c and Rv3425, from RD2 and RD11, respectively, on the basis of
      epitope mapping, in TB patients and BCG-vaccinated healthy individuals. Using a
      whole-blood gamma interferon release assay, a wide array of epitopes was
      recognized on both Rv1985c and Rv3425 in TB patients. Those epitopes that could
      specifically discriminate TB infection from BCG vaccination were carefully
      selected, and the most promising peptide pools from Rv1985c showed a sensitivity
      of 53.9% and a specificity of 95.5%. When the novel specific peptides from
      Rv1985c joined the diagnostic antigens in the QuantiFERON-TB Gold In-Tube (QFT
      IT) assay, the sensitivity was increased from 86.4% to 96.2%, with no drop in
      specificity. These results indicate that the peptide pools selected from Rv1985c
      and Rv3425 have the potential to diagnose TB infection by a method that may be
      routinely used in clinical laboratories.

PMID- 23136117
TI  - Acquisition of meningococcal serogroup W-135 carriage in Turkish Hajj pilgrims
      who had received the quadrivalent meningococcal polysaccharide vaccine.
AB  - Invasive meningococcal disease is a recognized public health problem worldwide,
      with a dynamic and changeable epidemiology. In Turkey, the second most common
      pathogenic meningococcal serogroup (after serogroup B) is W-135, including an
      epidemic in 2005, which has been strongly associated with Hajj pilgrims and their
      close contacts. In two studies conducted in 2010, we assessed meningococcal
      carriage in intending Turkish pilgrims to the Hajj when they attended to receive
      a plain polysaccharide vaccine against serogroups A, C, W-135, and Y and, upon
      their return, to determine the acquisition of meningococcal carriage by the
      pilgrims themselves and subsequently their household contacts. Nasopharyngeal
      swabs were obtained from pilgrims before the Hajj and upon their return. Swabs
      were then obtained from 39 household contacts of pilgrims who were shown to have
      acquired carriage during the Hajj. Of the 472 pilgrims before the Hajj, 63 (13%)
      were positive for meningococcal carriage, of which 52 cases (83%) were serogroup
      W-135. In the 296 pilgrims tested after the Hajj, 81 (27%) were positive for
      meningococcal carriage, including 74 (91%) with W-135. In 11 family members of
      pilgrims who acquired W-135 carriage at the Hajj, 10 (91%) had acquired carriage
      of serogroup W-135. This study illustrates the acquisition of meningococcal
      carriage, predominantly of serogroup W-135 by pilgrims attending the Hajj, and
      the transmission of this carriage to their family members on their return,
      explaining the source of W-135 meningococcal disease in Turkey.

PMID- 23136118
TI  - Listeria monocytogenes-derived listeriolysin O has pathogen-associated molecular
      pattern-like properties independent of its hemolytic ability.
AB  - There is a constant need for improved adjuvants to augment the induction of
      immune responses against tumor-associated antigens (TAA) during immunotherapy.
      Previous studies have established that listeriolysin O (LLO), a cholesterol
      dependent cytolysin derived from Listeria monocytogenes, exhibits multifaceted
      effects to boost the stimulation of immune responses to a variety of antigens.
      However, the direct ability of LLO as an adjuvant and whether it acts as a
      pathogen-associated molecular pattern (PAMP) have not been demonstrated. In this
      paper, we show that a detoxified, nonhemolytic form of LLO (dtLLO) is an
      effective adjuvant in tumor immunotherapy and may activate innate and cellular
      immune responses by acting as a PAMP. Our investigation of the adjuvant activity
      demonstrates that dtLLO, either fused to or administered as a mixture with a
      human papillomavirus type 16 (HPV-16) E7 recombinant protein, can augment
      antitumor immune responses and facilitate tumor eradication. Further mechanistic
      studies using bone marrow-derived dendritic cells suggest that dtLLO acts as a
      PAMP by stimulating production of proinflammatory cytokines and inducing
      maturation of antigen-presenting cells (APC). We propose that dtLLO is an
      effective adjuvant for tumor immunotherapy, and likely for other therapeutic
      settings.

PMID- 23136119
TI  - Observation of the Fe-CN and Fe-CO vibrations in the active site of [NiFe]
      hydrogenase by nuclear resonance vibrational spectroscopy.
AB  - Nuclear inelastic scattering of (57)Fe labeled [NiFe] hydrogenase is shown to
      give information on different states of the enzyme. It was thus possible to
      detect and assign Fe-CO and Fe-CN bending and stretching vibrations of the active
      site outside the spectral range of the Fe-S cluster normal modes.

PMID- 23136120
TI  - Routes to Hydrogen Bonding Chain-End Functionalized Polymers.
AB  - The contribution of supramolecular chemistry to polymer science opens new
      perspectives for the design of polymer materials exhibiting valuable properties
      and easier processability due to the dynamic nature of non-covalent interactions.
      Hydrogen bonding polymers can be used as supramolecular units for yielding larger
      assemblies that possess attractive features, arising from the combination of
      polymer properties and the responsiveness of hydrogen bonds. The post
      polymerization modification of reactive end-groups is the most common procedure
      for generating such polymers. Examples of polymerizations mediated by hydrogen
      bonding-functionalized precursors have also recently been reported. This
      contribution reviews the current synthetic routes toward hydrogen bonding sticker
      chain-end functionalized polymers. 

PMID- 23136121
TI  - Flavan-3-ol-enriched dark chocolate and white chocolate improve acute measures of
      platelet function in a gender-specific way--a randomized-controlled human
      intervention trial.
AB  - SCOPE: We examined whether flavan-3-ol-enriched dark chocolate, compared with
      standard dark and white chocolate, beneficially affects platelet function in
      healthy subjects, and whether this relates to flavan-3-ol bioavailability.
      METHODS AND RESULTS: A total of 42 healthy subjects received an acute dose of
      flavan-3-ol-enriched dark, standard dark or white chocolate, in random order.
      Blood and urine samples were obtained just before and 2 and 6 h after consumption
      for measurements of platelet function, and bioavailability and excretion of
      flavan-3-ols. Flavan-3-ol-enriched dark chocolate significantly decreased
      adenosine diphosphate-induced platelet aggregation and P-selectin expression in
      men (all p <= 0.020), decreased thrombin receptor-activating peptide-induced
      platelet aggregation and increased thrombin receptor-activating peptide-induced
      fibrinogen binding in women (both p <= 0.041), and increased collagen/epinephrine
      induced ex vivo bleeding time in men and women (p <= 0.042). White chocolate
      significantly decreased adenosine diphosphate-induced platelet P-selectin
      expression (p = 0.002) and increased collagen/epinephrine-induced ex vivo
      bleeding time (p = 0.042) in men only. Differences in efficacy by which flavan-3
      ols affect platelet function were only partially explained by concentrations of
      flavan-3-ols and their metabolites in plasma or urine. CONCLUSION: Flavan-3-ols
      in dark chocolate, but also compounds in white chocolate, can improve platelet
      function, dependent on gender, and may thus beneficially affect atherogenesis.

PMID- 23136122
TI  - Multiway admixture deconvolution using phased or unphased ancestral panels.
AB  - We describe a novel method for inferring the local ancestry of admixed
      individuals from dense genome-wide single nucleotide polymorphism data. The
      method, called MULTIMIX, allows multiple source populations, models population
      linkage disequilibrium between markers and is applicable to datasets in which the
      sample and source populations are either phased or unphased. The model is based
      upon a hidden Markov model of switches in ancestry between consecutive windows of
      loci. We model the observed haplotypes within each window using a multivariate
      normal distribution with parameters estimated from the ancestral panels. We
      present three methods to fit the model-Markov chain Monte Carlo sampling, the
      Expectation Maximization algorithm, and a Classification Expectation Maximization
      algorithm. The performance of our method on individuals simulated to be admixed
      with European and West African ancestry shows it to be comparable to HAPMIX, the
      ancestry calls of the two methods agreeing at 99.26% of loci across the three
      parameter groups. In addition to it being faster than HAPMIX, it is also found to
      perform well over a range of extent of admixture in a simulation involving three
      ancestral populations. In an analysis of real data, we estimate the contribution
      of European, West African and Native American ancestry to each locus in the
      Mexican samples of HapMap, giving estimates of ancestral proportions that are
      consistent with those previously reported.

PMID- 23136123
TI  - ATP-binding cassette G-subfamily transporter 2 regulates cell cycle progression
      and asymmetric division in mouse cardiac side population progenitor cells.
AB  - RATIONALE: After cardiac injury, cardiac progenitor cells are acutely reduced and
      are replenished in part by regulated self-renewal and proliferation, which occurs
      through symmetric and asymmetric cellular division. Understanding the molecular
      cues controlling progenitor cell self-renewal and lineage commitment is critical
      for harnessing these cells for therapeutic regeneration. We previously have found
      that the cell surface ATP-binding cassette G-subfamily transporter 2 (Abcg2)
      influences the proliferation of cardiac side population (CSP) progenitor cells,
      but through unclear mechanisms. OBJECTIVE: To determine the role of Abcg2 on cell
      cycle progression and mode of division in mouse CSP cells. METHODS AND RESULTS:
      Herein, using CSP cells isolated from wild-type and Abcg2 knockout mice, we found
      that Abcg2 regulates G1-S cell cycle transition by fluorescence ubiquitination
      cell cycle indicators, cell cycle-focused gene expression arrays, and confocal
      live-cell fluorescent microscopy. Moreover, we found that modulation of cell
      cycle results in transition from symmetric to asymmetric cellular division in CSP
      cells lacking Abcg2. CONCLUSIONS: Abcg2 modulates CSP cell cycle progression and
      asymmetric cell division, establishing a mechanistic link between this surface
      transporter and cardiac progenitor cell function. Greater understanding of
      progenitor cell biology and, in particular, the regulation of resident progenitor
      cell homeostasis is vital for guiding the future development of cell-based
      therapies for cardiac regeneration.

PMID- 23136124
TI  - Matrix-isolated hydrogen-bonded and van der Waals complexes of hydrogen peroxide
      with OCS and CS2.
AB  - Matrix isolation spectroscopy has been combined with ab initio calculations to
      characterize the 1:1 complexes of H2O2 with OCS and CS2. The infrared spectra of
      the argon and nitrogen matrices doped with H2O2 and OCS or CS2 have been measured
      and analyzed. The geometries of the complexes were optimized at the MP2/6
      311++G(3df,3pd) level of theory. Four structures were found for the OCS-H2O2
      complex and five for the CS2-H2O2 one; every pair of the corresponding structures
      showed close correspondence. For every optimized structure the interaction energy
      was partitioned according to the SAPT Scheme and the topological distribution of
      the charge density (AIM theory) was performed. The SAPT analysis and AIM results
      indicate that only one complex among the nine optimized ones is stabilized by the
      hydrogen bonding, namely the OCS-H2O2 one with the OH group of H2O2 bonded to an
      oxygen atom of OCS. The other structures are stabilized by van der Waals
      interaction. The spectra analysis evidences that at least two types of the
      complexes are trapped in the argon matrices including the most stable ones:
      hydrogen bonded structure in the case of the OCS-H2O2 complex and the structure
      stabilized by the S...H and C...O interactions in the case of the CS2-H2O2
      complex. The solid nitrogen environment triggers the formation of the structures
      of C2v symmetry with a sulfur atom of OCS or CS2 directed toward the center of O
      O bond of H2O2, stabilized by S...O interactions.

PMID- 23136125
TI  - Biomimetic reflectors fabricated using self-organising, self-aligning liquid
      crystal polymers.
AB  - The photograph shows a polymer reflector that mimics the colour and underlying
      molecular structure of a golden beetle. It is formed from self-organizing layers
      of photopolymerised liquid crystal. These require an aligning layer, but we show
      that a layer of the material can be used as to self-align subsequent coatings,
      enabling the construction of complex structures by sequential coating of
      engineered materials.

PMID- 23136126
TI  - Mixed (P=S/P=O)-stabilized geminal dianion: facile diastereoselective
      intramolecular C-H activations by a related ruthenium-carbene complex.
AB  - A new unsymmetrical geminal dianion that contained both a phosphine oxide moiety
      and a phosphine sulfide moiety has been synthesized. Its reactivity towards
      Ru(II) was explored, which led to the formation of a highly reactive carbene
      complex that evolved at room temperature to yield a kinetic orthometalated Ru(II)
      complex through C-H activation of the phenyl group of the phosphine oxide moiety.
      This insertion was found to be thermally reversible and a second C-H insertion
      occurred at a phenyl group of the phosphine sulfide moiety to form the
      thermodynamic orthometalated Ru(II) complex in a diastereospecific manner. DFT
      calculations fully rationalized the experimental findings in terms of the
      relative energies of the kinetic and thermodynamic products and allowed the
      mechanism of this process to be fully understood.

PMID- 23136127
TI  - Intraoperative fluid management and complications following pancreatectomy.
AB  - BACKGROUND: Considerable debate exists as to appropriate perioperative fluid
      management. Data from several studies suggest that the amount of fluid
      administered perioperatively influences surgical outcome. Pancreatic resection is
      a major procedure in which complications are common. We examined 1,030 sequential
      patients who had undergone pancreatic resection at Memorial Sloan-Kettering
      Cancer Center. We documented the prevalence and nature of their complications,
      and then correlated complications to intraoperative fluid administration.
      METHODS: We retrospectively examined 1,030 pancreatic resections performed at
      Memorial Sloan-Kettering Cancer Center between May 2004 and December 2009 from
      our pancreatic database. Intraoperative administration of colloid and crystalloid
      was obtained from anesthesia records, and complication data from our
      institutional database. RESULTS: The overall in-hospital mortality was 1.7%.
      Operative mortality was due predominantly to intraabdominal infection. Sixty
      percent of the mortality resulted from intraabdominal complications related to
      the procedure. We did not demonstrate a clinically significant relationship
      between intraoperative fluid administration and complications, although minor
      statistical significance was suggested. CONCLUSIONS: In this retrospective review
      of intraoperative fluid administration we were not able to demonstrate a
      clinically significant association between postoperative complications and
      intraoperative crystalloid and colloid fluid administration. A randomized
      controlled trial has been initiated to address this question.

PMID- 23136128
TI  - A novel function for the survival motoneuron protein as a translational
      regulator.
AB  - SMN1, the causative gene for spinal muscular atrophy (SMA), plays a housekeeping
      role in the biogenesis of small nuclear RNA ribonucleoproteins. SMN is also
      present in granular foci along axonal projections of motoneurons, which are the
      predominant cell type affected in the pathology. These so-called RNA granules
      mediate the transport of specific mRNAs along neurites and regulate mRNA
      localization, stability, as well as local translation. Recent work has provided
      evidence suggesting that SMN may participate in the assembly of RNA granules, but
      beyond that, the precise nature of its role within these structures remains
      unclear. Here, we demonstrate that SMN associates with polyribosomes and can
      repress translation in an in vitro translation system. We further identify the
      arginine methyltransferase CARM1 as an mRNA that is regulated at the
      translational level by SMN and find that CARM1 is abnormally up-regulated in
      spinal cord tissue from SMA mice and in severe type I SMA patient cells. We have
      previously characterized a novel regulatory pathway in motoneurons involving the
      SMN-interacting RNA-binding protein HuD and CARM1. Thus, our results suggest the
      existence of a potential negative feedback loop in this pathway. Importantly, an
      SMA-causing mutation in the Tudor domain of SMN completely abolished
      translational repression, a strong indication for the functional significance of
      this novel SMN activity in the pathology.

PMID- 23136129
TI  - The frontotemporal lobar degeneration risk factor, TMEM106B, regulates lysosomal
      morphology and function.
AB  - Haploinsufficiency of Progranulin (PGRN), a gene encoding a secreted
      glycoprotein, is a major cause of frontotemporal lobar degeneration with
      ubiquitin (FTLD-U) positive inclusions. Single nucleotide polymorphisms in the
      TMEM106B gene were recently discovered as a risk factor for FTLD-U, especially in
      patients with PGRN mutations. TMEM106B is also associated with cognitive
      impairment in amyotrophic lateral sclerosis patients. Despite these studies,
      little is known about TMEM106B at molecular and cellular levels and how TMEM106B
      contributes to FTLD. Here, we show that TMEM106B is localized in the late
      endosome/lysosome compartments and TMEM106B levels are regulated by lysosomal
      activities. Ectopic expression of TMEM106B induces morphologic changes of
      lysosome compartments and delays the degradation of endocytic cargoes by the
      endolysosomal pathway. Furthermore, overexpression of TMEM106B correlates with
      elevated levels of PGRN, possibly by attenuating lysosomal degradation of PGRN.
      These results shed light on the cellular functions of TMEM106B and the roles of
      TMEM106B in the pathogenesis of FTLD-U with PGRN mutations.

PMID- 23136130
TI  - Aptamer-functionalized, ultra-small, monodisperse silica nanoconjugates for
      targeted dual-modal imaging of lymph nodes with metastatic tumors.

PMID- 23136131
TI  - Photo-controlled hierarchical assembly and fusion of coumarin-containing
      polydiacetylene vesicles.
AB  - Herein, we synthesize a coumarin-substituted diacetylene monomer (CODA) and
      report the novel photo-controlled reversible assembly and disassembly behavior of
      the polymerized CODA (PCODA) vesicles. The photo-triggered dimerization and
      cleavage reactions of the coumarin groups within the surface of the adjacent
      PCODA vesicles can be utilized as the driving force to induce assembly and
      disassembly of PCODA vesicles. Moreover, the boundary of PCODA vesicles in the
      aggregates becomes more obscure when the irradiation time exceeds 30 min. Fusion
      occurs upon close docking of target membranes, driven by sufficient dimerization
      of the coumarin groups within the surface of PCODA vesicles.

PMID- 23136132
TI  - A chiral self-assembled monolayer derived from a resolving agent and its
      performance as a crystallization template for an organic compound from organic
      solvents.
AB  - A new chiral nonracemic thiol derived from a popular acidic resolving agent that
      incorporates a cyclic disubstituted phosphate group (phencyphos) has been
      prepared in enantiomerically pure form. The stereochemistry and absolute
      configuration were established by performing a single-crystal X-ray structural
      analysis of a synthetic intermediate. The thiol compound was used for the
      preparation of self-assembled monolayers (SAMs) on both monocrystalline and
      polycrystalline metallic gold, which have very different surface roughness. The
      monolayers were used to promote the nucleation and growth of crystals from
      nonaqueous solutions of an organic molecule (the parent phencyphos) of similar
      structure to the compound present in the monolayer. The template layers influence
      the nucleation and growth of the phencyphos crystals despite the lack of two
      dimensional order in the surfaces. Heterogeneous nucleation of phencyphos takes
      place upon evaporation of either CHCl(3)  or isopropanol solutions of the
      compound on the SAM surfaces, where the evaporation rate merely influences the
      size and homogeneity of the crystals. The roughness of the surface also plays an
      important role; the polycrystalline gold produces more homogeneous samples
      because of the greater number of nucleation sites. Clear evidence for nucleation
      and growth on the surfaces is shown by scanning electron microscopy. The
      variation in crystal form achieved by using different surfaces and solvents
      suggests that the layers are applicable for the preparation of organic crystals
      from organic solutions.

PMID- 23136134
TI  - Acidic water monolayer on ruthenium(0001).

PMID- 23136133
TI  - Folate, alcohol, and liver disease.
AB  - Alcoholic liver disease (ALD) is typically associated with folate deficiency,
      which is the result of reduced dietary folate intake, intestinal malabsorption,
      reduced liver uptake and storage, and increased urinary folate excretion. Folate
      deficiency favors the progression of liver disease through mechanisms that
      include its effects on methionine metabolism with consequences for DNA synthesis
      and stability and the epigenetic regulation of gene expression involved in
      pathways of liver injury. This paper reviews the pathogenesis of ALD with
      particular focus on ethanol-induced alterations in methionine metabolism, which
      may act in synergy with folate deficiency to decrease antioxidant defense as well
      as DNA stability while regulating epigenetic mechanisms of relevant gene
      expressions. We also review the current evidence available on potential
      treatments of ALD based on correcting abnormalities in methionine metabolism and
      the methylation regulation of relevant gene expressions.

PMID- 23136135
TI  - Maternal menopause as a predictor of anti-Mullerian hormone level and antral
      follicle count in daughters during reproductive age.
AB  - STUDY QUESTION: Is the ovarian reserve in a woman at a given age associated with
      her mother's age at menopause? SUMMARY ANSWER: We demonstrated a significant,
      positive association between age at maternal menopause and serum anti-Mullerian
      hormone (AMH) levels and antral follicle count (AFC) in daughters. The rate of
      decline in serum-AMH level and AFC is also associated with age at maternal
      menopause. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: The association between
      menopausal age in mothers and daughters has been established through several
      epidemiological studies. This paper shows that early maternal menopause is
      related to an advanced depletion of the ovarian reserve and that late maternal
      menopause is related to a delayed depletion. STUDY DESIGN AND SIZE: Cross
      sectional data were obtained from a prospective cohort study of 863 women. The
      study comprised 527 participants from this prospective cohort whose mothers' age
      at natural menopause was known. PARTICIPANTS, SETTING AND METHODS: Participants
      were recruited from female health care workers aged 20-40 years employed at
      Copenhagen University Hospital, Rigshospitalet, and were enrolled in the study
      between September 2008 and February 2010. The response rate was 52.1%. Endocrine
      and ovarian parameters related to reproductive ageing (AMH and AFC) were assessed
      by serum AMH analyses and transvaginal ovarian sonography on cycle Day 2-5. Data
      on reproductive history, including age at natural maternal menopause, were
      obtained through an internet-based questionnaire. We used an analysis of
      covariance model with serum-AMH and AFC as outcomes, age as the quantitative
      predictor and onset of maternal menopause as the categorical predictor, with
      further adjustments for BMI, use of oral contraceptives, participants' smoking
      habits and prenatal smoking exposure. MAIN FINDINGS: We found a significant
      effect of age at maternal menopause on both serum AMH levels (P < 0.001) and AFC
      (P = 0.005). Median serum-AMH concentration declined by 8.6% per year [95%
      confidence interval (CI): 6.4-10.8%, P < 0.001] in the group with early maternal
      menopausal age (<= 45 years), by 6.8% per year (95% CI: 5.0-8.6%, P < 0.001) in
      the group with normal maternal menopausal age (46-54 years) and by 4.2% per year
      (95% CI: 2.0-6.4%, P < 0.001) in the group with late maternal menopausal age (>=
      55 years). Median AFC declined by 5.8% per year (95% CI: 4.0-7.5%, P < 0.001) in
      the group with early maternal menopausal age (<= 45 years), by 4.7% per year (95%
      CI: 3.3-6.1%, P < 0.001) in the group with normal maternal menopausal age (46-54
      years) and by 3.2% per year (95% CI: 1.4-4.9%, P < 0.001) in the group with late
      maternal age (>= 55 years) at menopause. BIAS, LIMITATIONS AND GENERALIZABILITY:
      Information on 'age at maternal menopause' was obtained retrospectively and may
      be prone to recall bias and digit preference. The study population consisted of
      health care workers, which implies a potential selection bias. Finally, the cross
      sectional nature of the data limits the generalizability. STUDY FUNDING/POTENTIAL
      COMPETING INTERESTS: This study was co-financed by PhD scholarships where funding
      was covered by the Danish Agency for Science, Technology and Innovation,
      Copenhagen Graduate School of Health Science (CGSHS) and the Fertility Clinic at
      Copenhagen University Hospital, Rigshopitalet. No competing interests are
      declared.

PMID- 23136136
TI  - Nitric oxide donors for cardiovascular implant applications.
AB  - In an era of increased cardiovascular disease burden in the ageing population,
      there is great demand for devices that come in to contact with the blood such as
      heart valves, stents, and bypass grafts that offer life saving treatments. Nitric
      oxide (NO) elution from healthy endothelial tissue that lines the vessels
      maintains haemostasis throughout the vasculature. Surgical devices that release
      NO are desirable treatment options and N-diazeniumdiolates and S-nitrosothiols
      are recognized as preferred donor molecules. There is a keen interest to
      investigate newer methods by which NO donors can be retained within biomaterials
      so that their release and kinetic profiles can be optimized. A range of polymeric
      scaffolds incorporating microparticles and nanomaterials are presenting solutions
      to current challenges, and have been investigated in a range of clinical
      applications. This review outlines the application of NO donors for
      cardiovascular therapy using biomaterials that release NO locally to prevent
      thrombosis and intimal hyperplasia (IH) and enhance endothelialization in the
      fabrication of next generation cardiovascular device technology.

PMID- 23136137
TI  - Multivariate data analysis for finding the relevant fatty acids contributing to
      the melting fractions of cream.
AB  - BACKGROUND: The melting behaviour and fatty acid composition of cream from a
      total of 33 cows from four farms were analysed. Multivariate data analysis was
      used to identify the fatty acids that contributed most to the melting points and
      to differentiate between creams from different practical feeding regimes.
      RESULTS: It was demonstrated that the melting point of the medium melting
      fraction of milk fat was positively correlated with palmitic acid (C16:0),
      whereas it was negatively correlated with oleic acid (C18:1 cis9), conjugated
      linoleic acid (CLA cis9 trans11), vaccenic acid (C18:1 trans11), elaic acid
      (C18:1 trans9) and myristoleic acid (C14:1). The melting points of the high
      melting fractions could not be related to the fatty acid composition. Addition of
      palmitic acid-based fat supplement to the feeding ration in combination with a
      lower forage intake increased the amount of C16:0 and palmitoleic acid (C16:1) in
      milk fat, whereas it decreased the amount of stearic acid (C18:0) and C18:1 trans
      fatty acid. Average data on the melting behaviour of cream separated the farms
      into two groups where the main differences in feeding were the amounts of maize
      silage and rapeseed cake used. CONCLUSION: Multivariate analysis of data from
      individual cows identified the most relevant fatty acids contributing to the
      melting point of the medium melting fraction of cream. The fatty acid composition
      of milk fat could differentiate cream from different feeding strategies; however,
      owing to individual cow variation, it was not possible to extract clear
      correlations between feeding regime and melting behaviour of cream.

PMID- 23136139
TI  - Ghrelin suppresses secretion of gonadotropins in women.

PMID- 23136140
TI  - Genetic susceptibility loci for subtypes of breast cancer in an African American
      population.
AB  - BACKGROUND: Most genome-wide association studies (GWAS) have been carried out in
      European ancestry populations; no risk variants for breast cancer have been
      identified solely from African ancestry GWAS data. Few GWAS hits have replicated
      in African ancestry populations. METHODS: In a nested case-control study of
      breast cancer in the Black Women's Health Study (1,199 cases/1,948 controls), we
      evaluated index single-nucleotide polymorphisms (SNP) in 21 loci from GWAS of
      European or Asian ancestry populations, overall, in subtypes defined by estrogen
      receptor (ER) and progesterone receptor (PR) status (ER+/PR+, n = 336; ER-/PR-, n
      = 229), and in triple-negative breast cancer (TNBC, N = 81). To evaluate the
      contribution of genetic factors to population differences in breast cancer
      subtype, we also examined global percent African ancestry. RESULTS: Index SNPs in
      five loci were replicated, including three associated with ER-/PR- breast cancer
      (TERT rs10069690 in 5p15.33, rs704010 in 10q22.3, and rs8170 in 19p13.11): per
      allele ORs were 1.29 [95% confidence interval (CI) 1.04-1.59], P = 0.02, 1.52
      (95% CI 1.12-2.08), P = 0.01, and 1.30 (95% CI 1.01-1.68), P = 0.04,
      respectively. Stronger associations were observed for TNBC. Furthermore, cases in
      the highest quintile of percent African ancestry were three times more likely to
      have TNBC than ER+/PR+ cancer. CONCLUSIONS: These findings provide the first
      confirmation of the TNBC SNP rs8170 in an African ancestry population, and
      independent confirmation of the TERT ER- SNP. Furthermore, the risk of developing
      ER- breast cancer, particularly TNBC, increased with increasing proportion of
      global African ancestry. IMPACT: The findings illustrate the importance of
      genetic factors in the disproportionately high occurrence of TNBC in African
      American women.

PMID- 23136141
TI  - HPV vaccination among adolescent females from Appalachia: implications for
      cervical cancer disparities.
AB  - BACKGROUND: Appalachia is a geographic region with high cervical cancer incidence
      and mortality rates, yet little is known about human papillomavirus (HPV)
      vaccination in this region. We determined HPV vaccine coverage among adolescent
      females from Appalachia, made comparisons to non-Appalachian females, and
      examined how coverage differs across subregions within Appalachia. METHODS: We
      analyzed data from the National Immunization Survey-Teen 2008-2010 for adolescent
      females ages 13-17 (n = 1,951, Appalachian females and n = 25,468, non
      Appalachian females). We examined HPV vaccine initiation (receipt of at least one
      dose), completion (receipt of at least three doses), and follow-through
      (completion among initiators). Analyses used weighted logistic regression.
      RESULTS: HPV vaccine initiation [Appalachian = 40.8% vs. non-Appalachian = 43.6%;
      OR, 0.92; 95% confidence interval (CI), 0.79-1.07] and completion (Appalachian =
      27.7% vs. non-Appalachian = 25.3%; OR, 1.12; 95% CI, 0.95-1.32) were similar
      between Appalachian and non-Appalachian females. HPV vaccine follow-through was
      higher among Appalachian females than non-Appalachian females (67.8% vs. 58.1%;
      OR, 1.36; 95% CI, 1.07-1.72). Vaccination outcomes tended to be higher in the
      Northern (completion and follow-through) and South Central (follow-through)
      subregions of Appalachia compared with non-Appalachian United States. Conversely,
      vaccination outcomes tended to be lower in the Central (initiation and
      completion) and Southern (initiation and completion) subregions. CONCLUSIONS: In
      general, HPV vaccination in Appalachia is mostly similar to the rest of the
      United States. However, vaccination is lagging in regions of Appalachia where
      cervical cancer incidence and mortality rates are highest. IMPACT: Current
      cervical cancer disparities could potentially worsen if HPV vaccine coverage is
      not improved in regions of Appalachia with low HPV vaccine coverage.

PMID- 23136142
TI  - Sex offender treatment outcome, actuarial risk, and the aging sex offender in
      Canadian corrections: a long-term follow-up.
AB  - The present study is an examination of sex offender treatment outcome in a large
      national cohort of Canadian Federally incarcerated sex offenders followed up an
      average of 11.7 years postrelease. A brief actuarial risk scale (BARS), which
      predicted sexual and violent recidivism, was created for the purposes of the
      present study to control for risk-related differences between treated and
      untreated offenders. In total, 732 offenders were identified as having completed
      (n = 625) or not attended (n = 107) a sex offender treatment program and for whom
      sufficient information was available to complete the scale. Controlling for risk
      and individual differences in follow-up time using Cox regression survival
      analyses and an 8-year fixed follow-up period, treated sex offenders demonstrated
      significantly lower rates of violent, but not sexual, recidivism. When the
      treated and untreated groups were stratified by risk level, significant
      differences were observed only among moderate or high risk offenders. Some
      significant group differences also emerged on indicators of recidivism severity,
      with treated offenders demonstrating slower times to sexual reoffense and lower
      scores on a quantified metric of sexual and violent recidivism severity after
      controlling for risk. Differences in recidivism base rates between treated and
      untreated offenders were also larger in magnitude for younger offenders (i.e.,
      under age 50 at release), than for older offenders; however, interactions between
      age and treatment were not found. The findings are consistent with the risk
      principle and have possible implications regarding the dynamic nature of sexual
      violence risk. 

PMID- 23136143
TI  - Production of offspring after sperm chromosome screening: an experiment using the
      mouse model.
AB  - STUDY QUESTION: Is it possible to produce offspring after sperm chromosome
      screening? SUMMARY ANSWER: It is possible to produce zygotes after examining the
      genome of individual spermatozoa prior to embryo production. WHAT IS KNOWN
      ALREADY: Chromosomal aberrations in gametes are a major cause of pregnancy loss
      in women treated with assisted reproductive technology. However, to our
      knowledge, there are no reports on the successful genomic screening of
      spermatozoa, although some attempts have been made using the mouse as a model.
      STUDY DESIGN: To prevent the transmission of chromosomal aberrations from fathers
      to offspring, we performed sperm chromosome screening (SCS) prior to
      fertilization using the mouse as a model. The production of offspring after SCS
      consists of (i) replication of the sperm chromosomes, (ii) analysis of one copy
      of the replicated sperm chromosomes, (iii) construction of a zygote using another
      set of chromosomes and (iv) production of a transferable embryo. MATERIALS,
      SETTING, METHODS: A single spermatozoon of a male mouse, with or without a
      Robertsonian translocation, was injected into an enucleated oocyte to allow the
      replication of sperm chromosomes. One of the sister blastomeres of a haploid
      androgenic 2-cell embryo was used for chromosome analysis. The other blastomere
      was fused with an unfertilized oocyte, activated and allowed to develop to a
      blastocyst before transfer to a surrogate mother. MAIN RESULTS AND ROLE OF
      CHANCE: With high efficiency, we were able to analyze sperm chromosomes in a
      blastomere from the androgenic 2-cell embryos and culture zygotes, with and
      without aberrant chromosomes, to the blastocyst stage before embryo transfer. The
      karyotypes of the offspring faithfully reflected those of the blastomeres used
      for SCS. LIMITATIONS, REASONS FOR CAUTION: This study was conducted using a mouse
      model; whether or not the method is applicable to humans is not known. WIDER
      IMPLICATIONS OF THE FINDINGS: This study has shown that it is possible to produce
      zygotes without any paternally inherited aberrations by examining the genome of
      individual spermatozoa prior to embryo production.

PMID- 23136144
TI  - High ovarian response does not jeopardize ongoing pregnancy rates and increases
      cumulative pregnancy rates in a GnRH-antagonist protocol.
AB  - STUDY QUESTION: Is the ovarian response to controlled ovarian stimulation (COS)
      related to the ongoing pregnancy rate when taking into account the main
      covariates affecting the probabilities of pregnancy following fresh embryo
      transfer? SUMMARY ANSWER: In patients treated with corifollitropin alfa or daily
      recombinant FSH (rFSH) in a GnRH-antagonist protocol, a high ovarian response did
      not compromise ongoing pregnancy rates and increased cumulative pregnancy rates
      following fresh and frozen-thawed embryo transfer. WHAT IS KNOWN AND WHAT THIS
      PAPER ADDS: A strong association between the number of oocytes and pregnancy
      rates has been described but this is the first comprehensive analysis assessing
      important confounders that might affect pregnancy rates. STUDY DESIGN: In a
      large, prospective, double-blind, randomized trial (Engage; n = 1506), patients
      were treated with either a single dose of 150 MUg corifollitropin alfa or daily
      200 IU rFSH for the first 7 days of COS in a GnRH-antagonist (ganirelix)
      protocol. In this retrospective analysis, patients were categorized into five
      groups according to the number of oocytes retrieved (0-5, 6-9, 10-13, 14-18 and
      >18 oocytes). The number of good-quality embryos obtained and transferred, as
      well as the ongoing pregnancy rates, live birth rates and cumulative ongoing
      pregnancy rates per started cycle by group were evaluated. Univariate analysis
      was performed to identify factors that predict the chance of ongoing pregnancy.
      Logistic regression analysis on the dependent variables ongoing pregnancy and
      cumulative ongoing pregnancy, respectively, including oocyte category as an
      independent factor in the model, was performed by treatment group
      (corifollitropin alfa and rFSH) and overall. The likelihood of ongoing pregnancy
      and cumulative ongoing pregnancy was then evaluated taking into account ovarian
      response as well as other identified significant predictors of success.
      PARTICIPANTS AND SETTING: In total, 1506 patients had been randomized in a ratio
      of 1:1 to either of the treatment groups. Patients were aged <= 36 years and had
      a body weight >60 kg. MAIN RESULTS AND THE ROLE OF CHANCE: The ongoing pregnancy
      rates per started cycle increased in the corifollitropin alfa and rFSH groups
      from 31.9 and 31.3%, respectively, in the lowest response group (0-5 oocytes) to
      41.9 and 43.4% in the highest response group (>18 oocytes) with a significant
      linear trend (P = 0.04). The cumulative pregnancy rates taking frozen-thawed
      embryo transfers into account increased from 33.0 and 31.3% to 60.8 and 55.9% in
      the corifollitropin alfa and rFSH groups, respectively. Univariate logistic
      regression analyses of ongoing pregnancy showed significant effects for the
      following factors: embryo transfer (double or single, P < 0.01), region of
      treatment (North America or Europe, P < 0.01), progesterone level on the day of
      hCG (>1.5 or <= 1.5 ng/ml, P < 0.01), start day of the stimulation (cycle day 2
      or 3, P = 0.02) and age (P = 0.04). Logistic regression analysis of ongoing
      pregnancy using 10-13 oocytes as the reference category, per treatment group and
      overall revealed estimated odds ratios (OR) close to 1.0 versus the reference,
      without statistically significant differences with and without adjustment for
      significant predictive factors affecting pregnancy rates. Unadjusted OR for
      cumulative pregnancy reflected significantly lower odds of pregnancy for the
      lowest response group and significantly higher odds of pregnancy for the highest
      response group in comparison with the reference. When adjusted for the predictive
      factors, the cumulative ongoing pregnancy OR (95% confidence interval) of the
      highest response group versus the reference group was 1.87 (1.34-2.59) when the
      data of both treatment groups were pooled. BIAS, CONFOUNDING AND OTHER REASONS
      FOR CAUTION: The number of covariates included in the final model was limited to
      five major factors and not all other potentially significant predictive factors
      were available for evaluation. GENERALIZABILITY TO OTHER POPULATIONS: This
      analysis is limited to IVF patients with a regular menstrual cycle up to 36 years
      of age and a body weight >60 and <= 90 kg treated with a GnRH-antagonist protocol
      and cannot be extrapolated to other patient populations or treatment regimens.

PMID- 23136145
TI  - Factors related to unstained areas in whole ewe ovaries perfused with a metabolic
      marker.
AB  - STUDY QUESTION: What factors are associated with the presence of areas unexposed
      to the perfusate after whole ovary perfusion? SUMMARY ANSWER: Over half the
      ovaries perfused with the metabolic marker methylthiazolyl blue tetrazolium (MTT)
      were incompletely stained. Incomplete staining was statistically significantly
      associated with a small ovarian slice surface area, inexperience of the
      experimenter, and the presence of a corpus luteum. WHAT IS KNOWN ALREADY: Whole
      ovary cryopreservation followed by vascular auto-transplantation has provided
      poor outcomes as an alternative way to safeguard fertility. Perfusion, commonly
      used to expose the ovaries to cryoprotectants, may miss areas excluded from the
      vascular network, explaining subsequent poor ovarian functionality. STUDY DESIGN,
      SIZE, DURATION: An observational study of 360 ewe ovaries stained by in vitro
      perfusion with MTT as a qualitative marker of tissue blood supply was performed.
      A logistic regression model was built to identify factors associated with
      incomplete ovary staining. MATERIALS, SETTING, METHODS: Whole ewe ovaries with
      their vascular pedicles were perfused at 0.35 ml/min with 1 g/l MTT for 2 h at 39
      degrees C under 19 experimental conditions. The pedicles were removed and the
      ovaries cut in half sagittally and photographed. The unstained area of the slice
      surface was measured. Times from ovary collection to ovary rinsing and to MTT
      perfusion initiation, ovary weight and slice surface area, presence of a corpus
      luteum and operator experience (number of ovaries previously perfused) were
      recorded. Pedicle MTT staining was quantified at 564 nm after solubilization in
      alcohol. MAIN RESULTS AND THE ROLE OF CHANCE: Unstained areas were observed in
      64.4% of the ovaries. Multivariate analysis found that incomplete ovary staining
      was independently associated with lower experimenter experience (P < 0.02),
      smaller ovary slice surface area (P < 0.0001) and presence of a corpus luteum (P
      < 0.01). The presence of unstained areas was independent from experimental
      conditions. The rate of incomplete ovary staining decreased from 83 to 60% beyond
      the 80th perfused ovary (P < 0.0001). LIMITATIONS, REASONS FOR CAUTION:
      Descriptive study. WIDER IMPLICATIONS OF THE FINDINGS: Blood-supply impairments
      that result in incomplete perfusion might adversely affect outcomes after whole
      ovary cryopreservation. Improved perfusion techniques should enhance success.

PMID- 23136146
TI  - Cardiac surgical outcomes in abdominal solid organ (renal and hepatic) transplant
      recipients: a case-matched study.
AB  - OBJECTIVES: This study aims to investigate the outcomes of cardiac surgery in
      patients with abdominal solid organ transplants and to compare them with the case
      matched population undergoing cardiac surgery. METHODS: Data from all transplant
      recipients abdominal solid organ transplant (ASOT) N = 36 (30 renal and 6
      hepatic) who underwent cardiac surgery in a single centre during the period from
      January 1997 to December 2010 were collected from hospital transplant registries
      and the cardiac database. The transplant recipients were case matched (CM) with
      104 patients in terms of the variables of age, sex and the type of cardiac
      surgery. Follow-up data were obtained from medical records and by a set of
      questionnaire through telephonic interviews. RESULTS: Follow-up times were 4.5 +/
      3.2 and 3.9 +/- 3.2 years in the transplant and CM groups, respectively. Follow
      up in the transplant group was 100%. There was no 30-day mortality in the
      transplant group. Thirty-day combined major morbidities were 9% in the matched
      group vs 11% in the transplant patients (P = 0.6). Median length of stay was 6
      days (inter-quartile range, IQR 5.9) for ASOT vs 5 days (IQR 4.6) for CM (P <
      0.01). New dialysis was 8.3% in transplant patients compared with 0.96% in the
      matched population, while infection was 16.66 vs 0.42% in the CM cohort. There
      was no allograft failure/dysfunction at the time of death or latest follow-up.
      Late deaths were 8 of 36 (22%) in ASOT vs 6 of 104 (6%) in CM. Infection (63%)
      was the most frequent major cause of death in transplant patients. One-, 2-, 5-
      and 10-year survivals for ASOT vs CM were 94, 88, 80, 59 vs 99, 99, 91, 85%,
      respectively. Multivariate predictors of mortality were increasing age (hazard
      ratio, HR 1.1, 95% confidence interval, CI 1.04-1.18; P = 0.003) and solid organ
      transplantation (HR 3.44, CI 1.19-9.98; P = 0.023). CONCLUSIONS: Cardiac surgery
      can be performed in patients with abdominal solid organ tranpslant recipients
      with acceptable early morbidity and mortality. However, long-term survival in
      transplant patients is poor. Infection remains the most common cause of death.

PMID- 23136147
TI  - Analysing cognitive test data: Distributions and non-parametric random effects.
AB  - An important assumption in many linear mixed models is that the conditional
      distribution of the response variable is normal. This assumption is violated when
      the models are fitted to an outcome variable that counts the number of correctly
      answered questions in a questionnaire. Examples include investigations of
      cognitive decline where models are fitted to Mini Mental State Examination
      scores, the most widely used test to measure global cognition. Mini Mental State
      Examination scores take integer values in the 0-30 range, and its distribution
      has strong ceiling and floor effects. This article explores alternative
      distributions for the outcome variable in mixed models fitted to mini mental
      state examination scores from a longitudinal study of ageing. Model fit improved
      when a beta-binomial distribution was chosen as the distribution for the response
      variable.

PMID- 23136148
TI  - Comparison of four methods for deriving hospital standardised mortality ratios
      from a single hierarchical logistic regression model.
AB  - There is interest in deriving case-mix adjusted standardised mortality ratios so
      that comparisons between healthcare providers, such as hospitals, can be
      undertaken in the controversial belief that variability in standardised mortality
      ratios reflects quality of care. Typically standardised mortality ratios are
      derived using a fixed effects logistic regression model, without a hospital term
      in the model. This fails to account for the hierarchical structure of the data -
      patients nested within hospitals - and so a hierarchical logistic regression
      model is more appropriate. However, four methods have been advocated for deriving
      standardised mortality ratios from a hierarchical logistic regression model, but
      their agreement is not known and neither do we know which is to be preferred. We
      found significant differences between the four types of standardised mortality
      ratios because they reflect a range of underlying conceptual issues. The most
      subtle issue is the distinction between asking how an average patient fares in
      different hospitals versus how patients at a given hospital fare at an average
      hospital. Since the answers to these questions are not the same and since the
      choice between these two approaches is not obvious, the extent to which profiling
      hospitals on mortality can be undertaken safely and reliably, without resolving
      these methodological issues, remains questionable.

PMID- 23136149
TI  - Correlation of histopathology, urinary biomarkers, and gene expression responses
      following hexachloro-1:3-butadiene-induced acute nephrotoxicity in male Hanover
      Wistar rats: a 28-day time course study.
AB  - Hexachloro-1:3-butadiene (HCBD) causes segment-specific injury to the proximal
      renal tubule. A time course study of traditional and more recently proposed
      urinary biomarkers was performed in male Hanover Wistar rats receiving a single
      intraperitoneal (ip) injection of 45 mg/kg HCBD. Animals were killed on days 1,
      2, 3, 4, 5, 6, 7, 10, 14, and 28 postdosing and the temporal response of renal
      biomarkers was characterized using kidney histopathology, urinary and serum
      biochemistry, and gene expression. Histopathologic evidence of tubular
      degeneration was seen from day 1 until day 3 postdosing and correlated with
      increased urinary levels of alpha-glutathione S-transferase (alpha-GST), albumin,
      glucose, and kidney injury molecule-1 (KIM-1), and increased gene expression of
      KIM-1, NAD(P)H dehydrogenase, quinone 1, and heme oxygenase (decycling) 1.
      Histopathologic evidence of tubular regeneration was seen from day 2 postdosing
      and correlated with raised levels of urinary KIM-1 and osteopontin and increased
      gene expression of KIM-1 and annexin A7. Traditional renal biomarkers generally
      demonstrated low sensitivity. It is concluded that in rat proximal tubular
      injury, measurement of a range of renal biomarkers, in conjunction with gene
      expression analysis, provides an understanding of the extent of degenerative
      changes induced in the kidney and the process of regeneration. 

PMID- 23136150
TI  - Editorial policy on computational, simulation and/or robotic papers.

PMID- 23136151
TI  - A JEB classic on fish exercise.

PMID- 23136152
TI  - Feel, smell and see in an egg: emergence of perception and learning in an
      immature invertebrate, the cuttlefish embryo.
AB  - It is now well established that prenatal sensory experience affects development
      itself and has long-term consequences in terms of postnatal behavior. This study
      focused on the functionality of the sensory system in cuttlefish in ovo. Embryos
      of stage 23, 25 and 30 received a tactile, chemical or visual stimulus. An
      increase of mantle contraction rhythm was taken to indicate a behavioral response
      to the stimulus. We clearly demonstrated that tactile and chemical systems are
      functional from stage 23, whereas the visual system is functional only from stage
      25. At stage 25 and 30, embryos were also exposed to a repeated light stimulus.
      Stage 30 embryos were capable of habituation, showing a progressive decrease in
      contractions across stimulations. This process was not due to fatigue as we
      observed response recovery after a dishabituation tactile stimulus. This study is
      the first to show that cuttlefish embryos behaviorally respond to stimuli of
      different modalities and that the visual system is the last to become functional
      during embryonic development, as in vertebrate embryos. It also provides new
      evidence that the memory system develops in ovo in cuttlefish.

PMID- 23136153
TI  - Dine or dash? Turbulence inhibits blue crab navigation in attractive-aversive
      odor plumes by altering signal structure encoded by the olfactory pathway.
AB  - Blue crabs can distinguish and navigate to attractive (food) odors even when
      aversive odors (injured crab metabolites) are released nearby. Blue crabs in
      these conditions detect the aversive odor and avoid it, but find the attractive
      source with nearly the same success rate as when the attractive source is
      presented alone. Spatially and temporally distinct odor filaments appear to
      signal to foragers that the two odor sources are not co-located, and hence
      navigating to the attractive odor entails an acceptable risk of predation.
      However, environmentally produced turbulence suppresses tracking by homogenizing
      the two odors; blue crabs fail to track to the attractive source when the
      aversive source is present, even though turbulence does not substantially inhibit
      tracking to the attractive source alone. Removal of sensory input from
      aesthetascs on the antennules, but not chemosensors on the legs, rescues
      navigation to attractive-aversive dual plumes in turbulent conditions. These
      results suggest that mixing in the natural environment may amplify the effects of
      predators by suppressing tracking to food odors when aversive cues are present,
      and that the olfactory pathway mediates the response.

PMID- 23136154
TI  - Beyond the Jamming Avoidance Response: weakly electric fish respond to the
      envelope of social electrosensory signals.
AB  - Recent studies have shown that central nervous system neurons in weakly electric
      fish respond to artificially constructed electrosensory envelopes, but the
      behavioral relevance of such stimuli is unclear. Here we investigate the
      possibility that social context creates envelopes that drive behavior. When
      Eigenmannia virescens are in groups of three or more, the interactions between
      their pseudo-sinusoidal electric fields can generate 'social envelopes'. We
      developed a simple mathematical prediction for how fish might respond to such
      social envelopes. To test this prediction, we measured the responses of E.
      virescens to stimuli consisting of two sinusoids, each outside the range of the
      Jamming Avoidance Response (JAR), that when added to the fish's own electric
      field produced low-frequency (below 10 Hz) social envelopes. Fish changed their
      electric organ discharge (EOD) frequency in response to these envelopes, which we
      have termed the Social Envelope Response (SER). In 99% of trials, the direction
      of the SER was consistent with the mathematical prediction. The SER was strongest
      in response to the lowest initial envelope frequency tested (2 Hz) and depended
      on stimulus amplitude. The SER generally resulted in an increase of the envelope
      frequency during the course of a trial, suggesting that this behavior may be a
      mechanism for avoiding low-frequency social envelopes. Importantly, the direction
      of the SER was not predicted by the superposition of two JAR responses: the SER
      was insensitive to the amplitude ratio between the sinusoids used to generate the
      envelope, but was instead predicted by the sign of the difference of difference
      frequencies.

PMID- 23136155
TI  - Structure, innervation and response properties of integumentary sensory organs in
      crocodilians.
AB  - Integumentary sensory organs (ISOs) are densely distributed on the jaws of
      crocodilians and on body scales of members of the families Crocodilidae and
      Gavialidae. We examined the distribution, anatomy, innervation and response
      properties of ISOs on the face and body of crocodilians and documented related
      behaviors for an alligatorid (Alligator mississippiensis) and a crocodylid
      (Crocodylus niloticus). Each of the ISOs (roughly 4000 in A. mississippiensis and
      9000 in C. niloticus) was innervated by networks of afferents supplying multiple
      different mechanoreceptors. Electrophysiological recordings from the trigeminal
      ganglion and peripheral nerves were made to isolate single-unit receptive fields
      and to test possible osmoreceptive and electroreceptive functions. Multiple small
      (<0.1 mm(2)) receptive fields, often from a single ISO, were recorded from the
      premaxilla, the rostral dentary, the gingivae and the distal digits. These
      responded to a median threshold of 0.08 mN. The less densely innervated caudal
      margins of the jaws had larger receptive fields (>100 mm(2)) and higher
      thresholds (13.725 mN). Rapidly adapting, slowly adapting type I and slowly
      adapting type II responses were identified based on neuronal responses. Several
      rapidly adapting units responded maximally to vibrations at 20-35 Hz, consistent
      with reports of the ISOs' role in detecting prey-generated water surface ripples.
      Despite crocodilians' armored bodies, the ISOs imparted a mechanical sensitivity
      exceeding that of primate fingertips. We conclude that crocodilian ISOs have
      diverse functions, including detection of water movements, indicating when to
      bite based on direct contact of pursued prey, and fine tactile discrimination of
      items held in the jaws.

PMID- 23136156
TI  - Mechanism of loss of Kv11.1 K+ current in mutant T421M-Kv11.1-expressing rat
      ventricular myocytes: interaction of trafficking and gating.
AB  - BACKGROUND: Type 2 long QT syndrome involves mutations in the human ether a-go-go
      related gene (hERG or KCNH2). T421M, an S1 domain mutation in the Kv11.1 channel
      protein, was identified in a resuscitated patient. We assessed its biophysical,
      protein trafficking, and pharmacological mechanisms in adult rat ventricular
      myocytes. METHODS AND RESULTS: Isolated adult rat ventricular myocytes were
      infected with wild-type (WT)-Kv11.1- and T421M-Kv11.1-expressing adenovirus and
      analyzed with the use of patch clamp, Western blot, and confocal imaging
      techniques. Expression of WT-Kv11.1 or T421M-Kv11.1 produced peak tail current
      (I(Kv11.1)) of 8.78+/-1.18 and 1.91+/-0.22 pA/pF, respectively. Loss of mutant
      I(Kv11.1) resulted from (1) a partially trafficking-deficient channel protein
      with reduced cell surface expression and (2) altered channel gating with a
      positive shift in the voltage dependence of activation and altered kinetics of
      activation and deactivation. Coexpression of WT+T421M-Kv11.1 resulted in
      heterotetrameric channels that remained partially trafficking deficient with only
      a minimal increase in peak I(Kv11.1) density, whereas the voltage dependence of
      channel gating became WT-like. In the adult rat ventricular myocyte model, both
      WT-Kv11.1 and T421M-Kv11.1 channels responded to beta-adrenergic stimulation by
      increasing I(Kv11.1). CONCLUSIONS: The T421M-Kv11.1 mutation caused a loss of
      I(Kv11.1) through interactions of abnormal protein trafficking and channel
      gating. Furthermore, for coexpressed WT+T421M-Kv11.1 channels, different dominant
      negative interactions govern protein trafficking and ion channel gating, and
      these are likely to be reflected in the clinical phenotype. Our results also show
      that WT and mutant Kv11.1 channels responded to beta-adrenergic stimulation.

PMID- 23136157
TI  - Neutrophil-derived matrix metalloproteinase 9 triggers acute aortic dissection.
AB  - BACKGROUND: Acute aortic dissection (AAD) is a life-threatening vascular disease
      without effective pharmaceutical therapy. Matrix metalloproteinases (MMPs) are
      implicated in the development of chronic vascular diseases including aneurysm,
      but the key effectors and mechanism of action remain unknown. To define further
      the role of MMPs in AAD, we screened circulating MMPs in AAD patients, and then
      generated a novel mouse model for AAD to characterize the mechanism of action.
      METHODS AND RESULTS: MMP9 and angiotensin II were elevated significantly in blood
      samples from AAD patients than in those from the patients with nonruptured
      chronic aortic aneurysm or healthy volunteers. Based on the findings, we
      established a novel AAD model by infusing angiotensin II to immature mice that
      had been received a lysyl oxidase inhibitor, beta-aminopropionitrile
      monofumarate. AAD was developed successfully in the thoracic aorta by angiotensin
      II administration to beta-aminopropionitrile monofumarate-treated wild-type mice,
      with an incidence of 20%, 80%, and 100% after 6, 12, and 24 hours, respectively.
      Neutrophil infiltrations were observed in the intima of the thoracic aorta, and
      the overexpression of MMP9 in the aorta was demonstrated by reverse transcription
      polymerase chain reaction, gelatin zymography, and immunohistochemistry. The
      incidence of AAD was reduced significantly by 40% following the administration of
      an MMP inhibitor and was almost blocked completely in MMP(-/-) mice without any
      influence on neutrophil infiltration. Neutrophil depletion by injection of anti
      granulocyte-differentiation antigen-1 (anti-Gr-1) antibody also significantly
      decreased the incidence of AAD. CONCLUSIONS: These data suggest that AAD is
      initiated by neutrophils that have infiltrated the aortic intima and released
      MMP9 in response to angiotensin II.

PMID- 23136158
TI  - Randomized comparison of sevoflurane versus propofol to reduce perioperative
      myocardial ischemia in patients undergoing noncardiac surgery.
AB  - BACKGROUND: Volatile anesthetics provide myocardial preconditioning in coronary
      surgery patients. We hypothesized that sevoflurane compared with propofol reduces
      the incidence of myocardial ischemia in patients undergoing major noncardiac
      surgery. METHODS AND RESULTS: We enrolled 385 patients at cardiovascular risk in
      3 centers. Patients were randomized to maintenance of anesthesia with sevoflurane
      or propofol. We recorded continuous ECG for 48 hours perioperatively, measured
      troponin T and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) on
      postoperative days 1 and 2, and evaluated postoperative delirium by the Confusion
      Assessment Method. At 6 and 12 months, we contacted patients by telephone to
      assess major adverse cardiac events. The primary end point was a composite of
      myocardial ischemia detected by continuous ECG and/or troponin elevation.
      Additional end points were postoperative NT-proBNP concentrations, major adverse
      cardiac events, and delirium. Patients and outcome assessors were blinded. We
      tested dichotomous end points by chi(2) test and NT-proBNP by Mann-Whitney test
      on an intention-to-treat basis. Myocardial ischemia occurred in 75 patients
      (40.8%) in the sevoflurane and 81 (40.3%) in the propofol group (relative risk,
      1.01; 95% confidence interval, 0.78-1.30). NT-proBNP release did not differ
      across allocation on postoperative day 1 or 2. Within 12 months, 14 patients
      (7.6%) suffered a major adverse cardiac event after sevoflurane and 17 (8.5%)
      after propofol (relative risk, 0.90; 95% confidence interval, 0.44-1.83). The
      incidence of delirium did not differ (11.4% versus 14.4%; P=0.379). CONCLUSIONS:
      Compared with propofol, sevoflurane did not reduce the incidence of myocardial
      ischemia in high-risk patients undergoing major noncardiac surgery. The
      sevoflurane and propofol groups did not differ in postoperative NT-proBNP
      release, major adverse cardiac events at 1 year, or delirium.

PMID- 23136159
TI  - A recipe for perioperative cardioprotection: what matters most? The ingredients
      or the chef?

PMID- 23136160
TI  - Hypothermia in comatose survivors from out-of-hospital cardiac arrest: pilot
      trial comparing 2 levels of target temperature.
AB  - BACKGROUND: It is recommended that comatose survivors of out-of-hospital cardiac
      arrest should be cooled to 32 degrees  to 34 degrees C for 12 to 24 hours.
      However, the optimal level of cooling is unknown. The aim of this pilot study was
      to obtain initial data on the effect of different levels of hypothermia. We
      hypothesized that deeper temperatures will be associated with better survival and
      neurological outcome. METHODS AND RESULTS: Patients were eligible if they had a
      witnessed out-of-hospital cardiac arrest from March 2008 to August 2011. Target
      temperature was randomly assigned to 32 degrees C or 34 degrees C. Enrollment was
      stratified on the basis of the initial rhythm as shockable or asystole. The
      target temperature was maintained during 24 hours followed by 12 to 24 hours of
      controlled rewarming. The primary outcome was survival free from severe
      dependence (Barthel Index score >=60 points) at 6 months. Thirty-six patients
      were enrolled in the trial (26 shockable rhythm, 10 asystole), with 18 assigned
      to 34 degrees C and 18 to 32 degrees C. Eight of 18 patients in the 32 degrees C
      group (44.4%) met the primary end point compared with 2 of 18 in the 34 degrees C
      group (11.1%) (log-rank P=0.12). All patients whose initial rhythm was asystole
      died before 6 months in both groups. Eight of 13 patients with initial shockable
      rhythm assigned to 32 degrees C (61.5%) were alive free from severe dependence at
      6 months compared with 2 of 13 (15.4%) assigned to 34 degrees C (log-rank
      P=0.029). The incidence of complications was similar in both groups except for
      the incidence of clinical seizures, which was lower (1 versus 11; P=0.0002) in
      patients assigned to 32 degrees C compared with 34 degrees C. On the contrary,
      there was a trend toward a higher incidence of bradycardia (7 versus 2; P=0.054)
      in patients assigned to 32 degrees C. Although potassium levels decreased to a
      greater extent in patients assigned to 32 degrees C, the incidence of hypokalemia
      was similar in both groups. CONCLUSIONS: The findings of this pilot trial suggest
      that a lower cooling level may be associated with a better outcome in patients
      surviving out-of-hospital cardiac arrest secondary to a shockable rhythm. The
      benefits observed here merit further investigation in a larger trial in out-of
      hospital cardiac arrest patients with different presenting rhythms. CLINICAL
      TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier:
      NCT01155622.

PMID- 23136161
TI  - Loss of angiomiR-126 and 130a in angiogenic early outgrowth cells from patients
      with chronic heart failure: role for impaired in vivo neovascularization and
      cardiac repair capacity.
AB  - BACKGROUND: MicroRNAs are key regulators of angiogenic processes. Administration
      of angiogenic early outgrowth cells (EOCs) or CD34(+) cells has been suggested to
      improve cardiac function after ischemic injury, in particular by promoting
      neovascularization. The present study therefore examines regulation of angiomiRs,
      microRNAs involved in angiogenesis, in angiogenic EOCs and circulating CD34(+)
      cells from patients with chronic heart failure (CHF) and the role for their
      cardiac repair capacity. METHODS AND RESULTS: Angiogenic EOCs and CD34(+) cells
      were isolated from patients with CHF caused by ischemic cardiomyopathy (n=45) and
      healthy subjects (n=35). In flow cytometry analyses, angiogenic EOCs were largely
      myeloid and positive for alternatively activated M2 macrophage markers. In vivo
      cardiac neovascularization and functional repair capacity were examined after
      transplantation into nude mice with myocardial infarction. Cardiac
      transplantation of angiogenic EOCs from healthy subjects markedly increased
      neovascularization and improved cardiac function, whereas no such effect was
      observed after transplantation of angiogenic EOCs from patients with CHF. Real
      time polymerase chain reaction analysis of 14 candidate angiomiRs, expressed in
      angiogenic EOCs, revealed a pronounced loss of angiomiR-126 and -130a in
      angiogenic EOCs from patients with CHF that was also observed in circulating
      CD34(+) cells. Anti-miR-126 transfection markedly impaired the capacity of
      angiogenic EOCs from healthy subjects to improve cardiac function. miR-126 mimic
      transfection increased the capacity of angiogenic EOCs from patients with CHF to
      improve cardiac neovascularization and function. CONCLUSIONS: The present study
      reveals a loss of angiomiR-126 and -130a in angiogenic EOCs and circulating
      CD34(+) cells from patients with CHF. Reduced miR-126 expression was identified
      as a novel mechanism limiting their capacity to improve cardiac
      neovascularization and function that can be targeted by miR-126 mimic
      transfection.

PMID- 23136162
TI  - Randomized trials in moderate ischemic mitral regurgitation: many questions,
      limited answers.

PMID- 23136165
TI  - Comparison of Bayesian random-effects and traditional life expectancy estimations
      in small-area applications.
AB  - There are several measures that summarize the mortality experience of a
      population. Of these measures, life expectancies are generally preferred based on
      their simpler interpretation and direct age standardization, which makes them
      directly comparable between different populations. However, traditional life
      expectancy estimations are highly inaccurate for smaller populations and
      consequently are seldom used in small-area applications. In this paper, the
      authors compare the relative performance of traditional life expectancy
      estimation with a Bayesian random-effects approach that uses correlations (i.e.,
      borrows strength) between different age groups, geographic areas, and sexes to
      improve the small-area life expectancy estimations. In the presented Monte Carlo
      simulations, the Bayesian random-effects approach outperforms the traditional
      approach in terms of bias, root mean square error, and coverage of the 95%
      confidence intervals. Moreover, the Bayesian random-effects approach is found to
      be usable for populations as small as 2,000 person-years at risk, which is
      considerably smaller than the minimum of 5,000 person-years at risk recommended
      for the traditional approach. As such, the proposed Bayesian random-effects
      approach is well-suited for estimation of life expectancies in small areas.

PMID- 23136163
TI  - Coronary artery bypass surgery with or without mitral valve annuloplasty in
      moderate functional ischemic mitral regurgitation: final results of the
      Randomized Ischemic Mitral Evaluation (RIME) trial.
AB  - BACKGROUND: The role of mitral valve repair (MVR) during coronary artery bypass
      grafting (CABG) in patients with moderate ischemic mitral regurgitation (MR) is
      uncertain. We conducted a randomized, controlled trial to determine whether
      repairing the mitral valve during CABG may improve functional capacity and left
      ventricular reverse remodeling compared with CABG alone. METHODS AND RESULTS:
      Seventy-three patients referred for CABG with moderate ischemic MR and an
      ejection fraction >30% were randomized to receive CABG plus MVR (34 patients) or
      CABG only (39 patients). The study was stopped early after review of interim
      data. At 1 year, there was a greater improvement in the primary end point of peak
      oxygen consumption in the CABG plus MVR group compared with the CABG group (3.3
      mL/kg/min versus 0.8 mL/kg/min; P<0.001). There was also a greater improvement in
      the secondary end points in the CABG plus MVR group compared with the CABG group:
      left ventricular end-systolic volume index, MR volume, and plasma B-type
      natriuretic peptide reduction of 22.2 mL/m(2), 28.2 mL/beat, and 557.4 pg/mL,
      respectively versus 4.4 mL/m(2) (P=0.002), 9.2 mL/beat (P=0.001), and 394.7 pg/mL
      (P=0.003), respectively. Operation duration, blood transfusion, intubation
      duration, and hospital stay duration were greater in the CABG plus MVR group.
      Deaths at 30 days and 1 year were similar in both groups: 3% and 9%, respectively
      in the CABG plus MVR group, versus 3% (P=1.00) and 5% (P=0.66), respectively in
      the CABG group. CONCLUSIONS: Adding mitral annuloplasty to CABG in patients with
      moderate ischemic MR may improve functional capacity, left ventricular reverse
      remodeling, MR severity, and B-type natriuretic peptide levels, compared with
      CABG alone. The impact of these benefits on longer term clinical outcomes remains
      to be defined.

PMID- 23136166
TI  - The relationship between root hydraulics and scion vigour across Vitis
      rootstocks: what role do root aquaporins play?
AB  - Vitis vinifera scions are commonly grafted onto rootstocks of other grape species
      to influence scion vigour and provide resistance to soil-borne pests and abiotic
      stress; however, the mechanisms by which rootstocks affect scion physiology
      remain unknown. This study characterized the hydraulic physiology of Vitis
      rootstocks that vary in vigour classification by investigating aquaporin (VvPIP)
      gene expression, fine-root hydraulic conductivity (Lp(r)), % aquaporin
      contribution to Lp(r), scion transpiration, and the size of root systems.
      Expression of several VvPIP genes was consistently greater in higher-vigour
      rootstocks under favourable growing conditions in a variety of media and in root
      tips compared to mature fine roots. Similar to VvPIP expression patterns, fine
      root Lp(r) and % aquaporin contribution to Lp(r) determined under both osmotic
      (Lp(r)(Osm)) and hydrostatic (Lp(r)(Hyd)) pressure gradients were consistently
      greater in high-vigour rootstocks. Interestingly, the % aquaporin contribution
      was nearly identical for Lp(r)(Osm) and Lp(r)(Hyd) even though a hydrostatic
      gradient would induce a predominant flow across the apoplastic pathway. In common
      scion greenhouse experiments, leaf area-specific transpiration (E) and total leaf
      area increased with rootstock vigour and were positively correlated with fine
      root Lp(r). These results suggest that increased canopy water demands for scion
      grafted onto high-vigour rootstocks are matched by adjustments in root-system
      hydraulic conductivity through the combination of fine-root Lp(r) and increased
      root surface area.

PMID- 23136167
TI  - Multiple impacts of the plant growth-promoting rhizobacterium Variovorax
      paradoxus 5C-2 on nutrient and ABA relations of Pisum sativum.
AB  - Resolving the physiological mechanisms by which rhizobacteria enhance plant
      growth is difficult, since many such bacteria contain multiple plant growth
      promoting properties. To understand further how the 1-aminocyclopropane-1
      carboxylate (ACC) deaminase (ACCd)-containing rhizobacterium Variovorax paradoxus
      5C-2 affects plant growth, the flows and partitioning of mineral nutrients and
      abscisic acid (ABA) and ABA metabolism were studied in pea (Pisum sativum) plants
      following rhizosphere bacterial inoculation. Although root architecture was not
      affected, inoculation increased root and shoot biomass, and stomatal conductance,
      by 20, 15, and 24%, respectively, and increased N, P, K, Ca, and Mg uptake by 16,
      81, 50, 46, and 58%, respectively. P deposition in inoculated plant roots was 4.9
      times higher than that in uninoculated controls. Rhizobacterial inoculation
      increased root to shoot xylem flows and shoot to root phloem flows of K by 1.8-
      and 2.1-fold, respectively. In control plants, major sinks for K deposition were
      the roots and upper shoot (43% and 49% of total uptake, respectively), while
      rhizobacterial inoculation increased K distribution to the lower shoot at the
      expense of other compartments (xylem, phloem, and upper shoot). Despite being
      unable to metabolize ABA in vitro, V. paradoxus 5C-2 decreased root ABA
      concentrations and accumulation by 40-60%. Although inoculation decreased xylem
      ABA flows, phloem ABA flows increased. Whether bacterial ACCd attenuates root to
      shoot ABA signalling requires further investigation, since ABA is critical to
      maintain growth of droughted plants, and ACCd-containing organisms have been
      advocated as a means of minimizing growth inhibition of plants in drying soil.

PMID- 23136168
TI  - Identification of quantitative trait loci controlling fibre length and lignin
      content in Arabidopsis thaliana stems.
AB  - Fibre properties and the biochemical composition of cell walls are important
      traits in many applications. For example, the lengths of fibres define the
      strength and quality of paper, and lignin content is a critical parameter for the
      use of biomass in biofuel production. Identifying genes controlling these traits
      is comparatively difficult in woody species, because of long generation times and
      limited amenability to high-resolution genetic mapping. To address this problem,
      this study mapped quantitative trait loci (QTLs) defining fibre length and lignin
      content in the Arabidopsis recombinant inbred line population Col-4 * Ler-0.
      Adapting high-throughput phenotyping techniques for both traits for measurements
      in Arabidopsis inflorescence stems identified significant QTLs for fibre length
      on chromosomes 2 and 5, as well as one significant QTL affecting lignin content
      on chromosome 2. For fibre length, total variation within the population was 208%
      higher than between parental lines and the identified QTLs explained 50.58% of
      the observed variation. For lignin content, the values were 261 and 26.51%,
      respectively. Bioinformatics analysis of the associated intervals identified a
      number of candidate genes for fibre length and lignin content. This study
      demonstrates that molecular mapping of QTLs pertaining to wood and fibre
      properties is possible in Arabidopsis, which substantially broadens the use of
      Arabidopsis as a model species for the functional characterization of plant
      genes.

PMID- 23136170
TI  - Positional headaches in a young Brazilian woman.

PMID- 23136169
TI  - Tinkering with meiosis.
AB  - Meiosis is at the heart of Mendelian heredity. Recently, much progress has been
      made in the understanding of this process, in various organisms. In the last 15
      years, the functional characterization of numerous genes involved in meiosis has
      dramatically deepened our knowledge of key events, including recombination, the
      cell cycle, and chromosome distribution. Through a constantly advancing tool set
      and knowledge base, a number of advances have been made that will allow
      manipulation of meiosis from a plant breeding perspective. This review focuses on
      the aspects of meiosis that can be tinkered with to create and propagate new
      varieties. We would like to dedicate this review to the memory of Simon W. Chan
      (1974-2012) (http://www.plb.ucdavis.edu/labs/srchan/).

PMID- 23136171
TI  - Perspective: artemisinin-resistant malaria and the wolf.

PMID- 23136172
TI  - Counter perspective: artemisinin resistance: facts, fears, and fables.

PMID- 23136173
TI  - Falling rates of malaria among U.S. military service members in Afghanistan
      substantiate findings of high compliance with daily chemoprophylaxis.

PMID- 23136175
TI  - Enabling factors for improved malaria chemoprophylaxis compliance.

PMID- 23136176
TI  - Diagnosis of radiographically occult lumbar spondylolysis in young athletes by
      magnetic resonance imaging.
AB  - BACKGROUND: The early stages of spondylolysis are extremely difficult to diagnose
      on plain radiography. Although several studies have examined changes in active
      spondylolysis on magnetic resonance imaging (MRI), no studies to date have
      determined the onset frequency of active spondylolysis detectable on MRI but
      occult on plain radiography. Moreover, the clinical features of active
      spondylolysis described in the literature do not facilitate the differentiation
      of this condition from other causes of low back pain. PURPOSE: This study aimed
      to evaluate the usefulness of MRI in diagnosing active spondylolysis early and in
      determining the prevalence of active spondylolysis in cases where findings were
      not detected on plain radiography. In addition, specific clinical features to aid
      in the early detection of active spondylolysis were evaluated. STUDY DESIGN:
      Cohort study; Level of evidence, 3. METHODS: Patients were 200 consecutive young
      athletes (144 boys and 56 girls; mean age, 14.1 +/- 1.5 y) with low back pain.
      All patients were examined by plain radiography (188 with negative findings and
      12 with unclear findings of spondylolysis) and MRI. Computed tomography (CT) was
      performed only for patients with high intensity changes of the pedicle observed
      on MRI. The presence or absence of low back pain was examined during lumbar spine
      extension and flexion. The Kemp test on the right and left sides and percussion
      of the vertebral spinous process were also performed. RESULTS: Ninety-seven
      (48.5%) patients showed evidence of active spondylolysis on MRI, findings that
      had been missed by plain radiography. These pars defects were organized into the
      following categories based on CT findings: nonlysis stage, 52; very early stage,
      37; late early stage, 22; progressive stage, 10; and terminal stage, 0. No
      significant physical examination factors were identified that could assist in the
      early detection of active spondylolysis. CONCLUSION: The MRI results suggest a
      high rate of active spondylolysis in young athletes with low back pain who test
      negative for spondylolysis on plain radiography. Magnetic resonance imaging
      appears to be useful in the early diagnosis of active spondylolysis, especially
      as we found no significant physical examination factors that could assist in
      early detection.

PMID- 23136177
TI  - Magnetic resonance imaging analysis of rotational alignment in patients with
      patellar dislocations.
AB  - BACKGROUND: The role of anatomic risk factors in patellofemoral instability is
      not yet fully understood, as they have been observed in patients either alone or
      in combination and in different degrees of severity. PURPOSE: To prospectively
      analyze rotational limb alignment in patients with patellofemoral instability and
      in controls using magnetic resonance imaging (MRI). STUDY DESIGN: Cross-sectional
      study; Level of evidence, 3. METHODS: Thirty patients (mean age, 22.9 y; range,
      12-41 y) with a history of patellar dislocation and 30 age- and sex-matched
      controls (mean age, 25.2 y; range, 16-37 y) were investigated. The patients
      underwent MRI of the leg at 1.5 T using a peripheral angiography coil and a T2
      weighted half-Fourier acquisition single-shot turbo spin echo (HASTE) sequence
      for measuring femoral antetorsion, tibial torsion, knee rotation, and mechanical
      axis deviation (MAD). The mean values of these parameters were compared between
      patients and controls. In addition, the patients underwent an assessment to
      determine the influence of rotational limb alignment on lateral trochlear
      inclination, trochlear facet asymmetry, trochlear depth, Insall-Salvati index,
      and tibial tuberosity-trochlear groove distance. RESULTS: Patients had 1.56-fold
      higher mean femoral antetorsion (20.3 degrees  +/- 10.4 degrees  vs 13.0 degrees 
      +/- 8.4 degrees ; P < .01) and 1.6-fold higher knee rotation (9.4 degrees  +/-
      5.0 degrees  vs 5.7 degrees  +/- 4.3 degrees ; P < .01) compared with controls.
      Moreover, patients had 2.9 times higher MAD (0.81 +/- 0.75 mm vs -0.28 +/- 0.87
      mm; P < .01). Differences in tibial torsion were not significant. Also, there
      were no significant correlations between parameters of rotational alignment and
      standard anatomic risk factors. CONCLUSION: Our results suggest that some
      patients with nontraumatic patellar instability have greater internal femoral
      rotation, greater knee rotation, and a tendency for genu valgum compared with
      healthy controls. Rotational malalignment may be a primary risk factor in
      patellar dislocation that has so far been underestimated.

PMID- 23136178
TI  - Microfracture for acetabular chondral defects in patients with femoroacetabular
      impingement: results at second-look arthroscopic surgery.
AB  - BACKGROUND: Microfracture is a proven technique to treat articular cartilage
      defects in the knee. However, there is little evidence in the literature to
      confirm the ability of microfracture to produce repair tissue in the hip joint.
      PURPOSE: The purpose of this study was to report the macroscopic and microscopic
      appearances of repair tissue after microfracture performed at hip arthroscopic
      surgery for isolated full-thickness acetabular cartilage defects in patients with
      femoroacetabular impingement (FAI). STUDY DESIGN: Case series; Level of evidence,
      4. METHODS: Twenty patients who underwent arthroscopic surgery for FAI had a
      localized full-thickness acetabular chondral defect treated by microfracture and
      then underwent a later second-look hip arthroscopic procedure. The size of the
      full-thickness defect was measured at the primary arthroscopic procedure. A
      visual assessment of the extent and quality of repair tissue was performed at
      second-look arthroscopic surgery. Two patients also had a biopsy of the repair
      tissue, which was studied histologically. RESULTS: At an average follow-up of 17
      months, 19 of the 20 patients had a mean fill of 96% +/- 7% with macroscopically
      good quality repair tissue. One patient had only a 25% fill with poor quality
      repair tissue. Histologically, the tissue was found to be primarily
      fibrocartilage with some staining for type II collagen in the region closest to
      the bone. CONCLUSION: Microfracture in the hip appears to be an effective
      technique that produces excellent coverage of the defect with good quality repair
      tissue on visual inspection and microscopic examination at an average follow-up
      of 17 months.

PMID- 23136179
TI  - The role of gender identity threat in perceptions of date rape and sexual
      coercion.
AB  - We experimentally investigated the effects of gender identity threat on men's and
      women's perceptions of date rape and sexual coercion. Results showed that men
      whose masculinity was threatened responded by blaming the victim and exonerating
      the perpetrator more, while threatened women respond by blaming male perpetrators
      more and placing less blame on female victims. Men's response to threats was more
      pronounced than women's, an asymmetry we attribute to the cultural devaluation of
      femininity. Our findings highlight the significance of masculinity concerns in
      perceptions of sexual violence and, more generally, the importance of perceiver
      context in views of violence against women.

PMID- 23136180
TI  - Justification of wife beating in rural Bangladesh: a qualitative analysis of
      gender differences in responses to survey questions.
AB  - Understanding attitudes about intimate partner violence (IPV) in cultural context
      is important for developing interventions to reduce it or mitigate its effects.
      This article presents qualitative findings from research conducted in rural
      Bangladesh to understand men's and women's responses to attitudinal questions
      about IPV. Both men and women often responded as if the questions were about
      their personal behavior. A few women said that their opinion did not matter.
      Women's responses were more sensitive than men's to contextual nuances in the
      questions, and men more often than women described their own attitudes as
      consistent with community norms.

PMID- 23136181
TI  - Women as easy scapegoats: witchcraft accusations and women as targets in tea
      plantations of India.
AB  - This article revisits a much-debated question: Why are women popular targets
      during witch hunts? By using in-depth interviews this article provides an answer.
      Women are easy targets or scapegoats for two reasons. First, it is widely
      believed in the community that was studied that witches do, in fact, exist, and
      the images of witches are always female. Second, tribal women hold lower
      positions than men in all social, political, and ritual matters, and this
      contributes to their vulnerability during the hunt for scapegoats. This article
      also highlights the roles that rumors play during manipulation of witchcraft
      accusations to gather support for witch hunts.

PMID- 23136182
TI  - A predictive theory of intentions to exit street-level prostitution.
AB  - Street-level prostitution is notoriously difficult to escape and rarely do women
      exit prostitution on their first attempt or without experiencing serious negative
      consequences to their physical or mental health. Unfortunately, few theories
      exist that explain the exiting process and those that do exist are difficult to
      test quantitatively. This article applies the integrative model of behavioral
      prediction to examine intentions to exit prostitution through attitudes, norms,
      and self-efficacy beliefs that underlie a woman's intention to exit prostitution.
      Constructs unique prostitution--agency and societal context--enhance the model.
      This theory may explain and predict an exit from street-level prostitution.

PMID- 23136183
TI  - Cutaneous metastasis of transitional cell carcinoma in 12 dogs.
AB  - In humans, cutaneous metastasis of transitional cell carcinoma (TCC) has been
      attributed to direct extension, lymphatic or hematogenous dissemination, or
      surgical implantation. The purpose of this study was to characterize the clinical
      and histologic features of cutaneous TCC metastasis, confirmed by uroplakin-III
      immunohistochemistry, in dogs. The 12 cases were 9 spayed female and 3 neutered
      male dogs, 6 to 14 years old (mean, 11 years). Four dogs had a history of urinary
      incontinence. Three had undergone abdominal surgery for TCC diagnosis or
      treatment. The primary neoplasms were 7 papillary infiltrating and 5 nonpapillary
      infiltrating TCC. Cutaneous lesions were detected at a mean of 123 days (median,
      38 days) after diagnosis of the primary TCC and appeared as plaques, papules, or
      nodules in, with 1 exception, perineal, inguinal, or ventral abdominal dermis or
      subcutis. Of 8 dogs with dermal TCC, 5 had epidermal erosion or ulceration. In 10
      dogs, TCC was detected in cutaneous lymphatic vessels, identified by endothelial
      immunoreactivity for Prox1. Metastases were also detected in lymph nodes in all
      dogs and at distant noncutaneous sites, usually the lungs, in 10 dogs. Mean
      survival after diagnosis was 162 days (median, 90 days). Despite medical
      treatment of 10 dogs after the development of cutaneous metastasis, remission was
      not achieved; 4 dogs had stable disease. Although TCC could have spread to skin
      by direct extension or lymphatic or vascular dissemination, the proximity of most
      cutaneous metastases to the vulva or prepuce raises the additional possibility of
      transepidermal spread through urine-scalded skin.

PMID- 23136184
TI  - End of life vignette. A last good-bye.

PMID- 23136185
TI  - Reversing effect of ring finger protein 43 inhibition on malignant phenotypes of
      human hepatocellular carcinoma.
AB  - It has been shown that Ring finger protein 43 (RNF43) is overexpressed in
      colorectal cancer and mediates cancer cell proliferation; however, its role in
      hepatocellular carcinoma (HCC) remains unknown. In this study, we found that
      RNF43 was frequently overexpressed in HCCs, and this overexpression was
      correlated with positive vascular invasion, poor tumor differentiation, and
      advanced tumor stage. Functional studies showed that knockdown of RNF43 could
      induce apoptosis and inhibit proliferation, invasion, colony formation, and
      xenograft growth of HCCs. Microarray-based gene profiling showed a total of 229
      genes differentially expressed after RNF43 knockdown, many of which are involved
      in oncogenic processes such as cell proliferation, cell adhesion, cell motility,
      cell death, DNA repair, and so on. These results suggest that RNF43 is involved
      in tumorigenesis and progression of HCCs and that antagonism of RNF43 may be
      beneficial for HCC treatment.

PMID- 23136186
TI  - A recombinant immunotoxin against the tumor-associated antigen mesothelin
      reengineered for high activity, low off-target toxicity, and reduced
      antigenicity.
AB  - SS1P is a recombinant immunotoxin (RIT) engineered for the targeted elimination
      of malignant cells that express the tumor-associated antigen mesothelin. It is
      composed of an antimesothelin antibody variable fragment (Fv) linked to a
      cytotoxic fragment of Pseudomonas exotoxin A (PE) that includes domains II and
      III of native PE. The clinical use of SS1P is limited by its propensity to induce
      neutralizing antibodies and to cause a dose-limiting capillary leak syndrome
      (CLS) in patients. In this article, we describe a reengineered SS1P with improved
      properties that overcome these deficits. The redesign of SS1P consists of (i)
      removing the bulk of PE domain II (residues 251-273 and 284-394 of native PE),
      leaving only an 11-residue furin cleavage site, (ii) adding a Gly-Gly-Ser peptide
      linker after the furin cleavage site, and (iii) replacing eight highly solvent
      exposed residues in the catalytic domain of PE. The new molecule, SS1-LR/GGS/8M,
      has cytotoxic activity comparable with SS1P on several mesothelin-expressing cell
      lines and remarkably improved activity on primary cells from patients with
      mesothelioma. In a mouse xenograft tumor model, high doses of SS1-LR/GGS/8M
      elicit antitumor activity superior to the activity of SS1P at its maximum
      tolerated dose. In addition, SS1-LR/GGS/8M has greatly decreased ability to cause
      CLS in a rat model and reduced antigenicity or reactivity with antibodies to the
      sera of patients previously treated with SS1P.

PMID- 23136187
TI  - Community treatment orders in Australia: rates and patterns of use.
AB  - OBJECTIVES: Community treatment orders (CTOs) allow clinicians to provide
      unconsented outpatient treatment to people living with mental illness. Though
      controversial and of uncertain efficacy, CTOs are used throughout Australia and
      internationally. We sought to determine the prevalence of CTO use in Australian
      states and territories, and to examine changes in the pattern of use over time.
      METHOD: Australian state and territory mental health review tribunals and health
      departments were surveyed for the most recent annual data on the total number of
      CTOs made and the total number of individual people placed on a CTO. RESULTS:
      Rates of CTO use range from 30.2 per 100,000 population (in Tasmania) to 98.8 per
      100,000 population (in Victoria). Use of CTOs in Australia is high by world
      standards, appears to be increasing over time, and varies significantly across
      jurisdictions. CONCLUSIONS: The high (by world standards), increasing and
      variable use of CTOs in Australia is concerning and raises important implications
      for mental health policymakers and legislators. Current mental health policy
      activity, particularly the new National Mental Health Commission, provides a
      unique opportunity to enhance transparency and accountability if regular and
      nationally uniform CTO data are collected and publically reported.

PMID- 23136188
TI  - Indicators of psychoses or psychoses as indicators: the relationship between
      Indigenous social disadvantage and serious mental illness.
AB  - OBJECTIVE: To explore the relationship between Indigenous social disadvantage and
      serious mental illness. CONCLUSIONS: Rapidly changing patterns of mental
      disorders in Indigenous populations indicate the importance of social
      determinants. Canadian research on Native American suicide has demonstrated a
      clear link between social control factors and one mental health issue - completed
      suicide - a finding with major social policy implications. This work has not been
      replicable in Australia, reflecting the particular political and social
      circumstances of Aboriginal and Torres Strait Islander populations. Recent
      research motivated by clinicians' observations of an increase in psychotic
      disorders in the Indigenous populations of Cape York and the Torres Strait has
      demonstrated that the prevalence is high and that there are within-population
      differences. Given similar exposure to social disadvantage, these findings raise
      the possibility of utilising Indigenous psychosis prevalence as a metric to
      inform a more nuanced understanding of the predictors of wider vulnerability and
      resilience at a setting level, and as a policy and service development lever.

PMID- 23136189
TI  - Expression profiling of archival tumors for long-term health studies.
AB  - PURPOSE: More than 20 million archival tissue samples are stored annually in the
      United States as formalin-fixed, paraffin-embedded (FFPE) blocks, but RNA
      degradation during fixation and storage has prevented their use for
      transcriptional profiling. New and highly sensitive assays for whole
      transcriptome microarray analysis of FFPE tissues are now available, but
      resulting data include noise and variability for which previous expression array
      methods are inadequate. EXPERIMENTAL DESIGN: We present the two largest whole
      genome expression studies from FFPE tissues to date, comprising 1,003 colorectal
      cancer (CRC) and 168 breast cancer samples, combined with a meta-analysis of 14
      new and published FFPE microarray datasets. We develop and validate quality
      control (QC) methods through technical replication, independent samples,
      comparison to results from fresh-frozen tissue, and recovery of expected
      associations between gene expression and protein abundance. RESULTS: Archival
      tissues from large, multicenter studies showed a much wider range of
      transcriptional data quality relative to smaller or frozen tissue studies and
      required stringent QC for subsequent analysis. We developed novel methods for
      such QC of archival tissue expression profiles based on sample dynamic range and
      per-study median profile. This enabled validated identification of gene
      signatures of microsatellite instability and additional features of CRC, and
      improved recovery of associations between gene expression and protein abundance
      of MLH1, FASN, CDX2, MGMT, and SIRT1 in CRC tumors. CONCLUSIONS: These methods
      for large-scale QC of FFPE expression profiles enable study of the cancer
      transcriptome in relation to extensive clinicopathological information, tumor
      molecular biomarkers, and long-term lifestyle and outcome data.

PMID- 23136190
TI  - Identification of serum proton NMR metabolomic fingerprints associated with
      hepatocellular carcinoma in patients with alcoholic cirrhosis.
AB  - PURPOSE: Metabolomics depicts metabolic changes in biologic systems using a
      multiparametric analysis technique. This study assessed the metabolomic profiles
      of serum, obtained by proton nuclear magnetic resonance (NMR) spectroscopy, from
      cirrhotic patients with and without hepatocellular carcinoma (HCC). EXPERIMENTAL
      DESIGN: The study included 154 consecutive patients with compensated biopsy
      proven alcoholic cirrhosis. Among these, 93 had cirrhosis without HCC, 28 had
      biopsy-proven HCC within the Milan criteria and were eligible for curative
      treatment (small HCC), and 33 had HCC outside the Milan criteria (large HCC).
      Proton spectra were acquired at 500 MHz. An orthogonal partial latent structure
      [orthogonal projection to latent structure (OPLS)] analysis model was built to
      discriminate large HCC spectra from cirrhotic spectra. Small HCC spectra were
      secondarily projected using previously built OPLS discriminant components.
      RESULTS: The OPLS model showed discrimination between cirrhotic and large HCC
      spectra. Metabolites that significantly increased with large HCC were glutamate,
      acetate, and N-acetyl glycoproteins, whereas metabolites that correlated with
      cirrhosis were lipids and glutamine. Projection of small HCC samples into the
      OPLS model showed a heterogeneous distribution between large HCC and cirrhotic
      samples. Small HCC patients with metabolomic profile similar to those of large
      HCC group had higher incidences of recurrence or death during follow-up.
      CONCLUSIONS: Serum NMR-based metabolomics identified metabolic fingerprints that
      could be specific to large HCC in cirrhotic livers. From a metabolomic
      standpoint, some patients with small HCC, who are eligible for curative
      treatments, seem to behave as patients with advanced cancerous disease. It would
      be useful to further prospectively investigate these patients to define a
      subgroup with a worse prognosis.

PMID- 23136191
TI  - Phosphoinositide 3-kinase (PI3K) pathway alterations are associated with
      histologic subtypes and are predictive of sensitivity to PI3K inhibitors in lung
      cancer preclinical models.
AB  - PURPOSE: Class 1 phosphatidylinositol 3-kinase (PI3K) plays a major role in cell
      proliferation and survival in a wide variety of human cancers. Here, we
      investigated biomarker strategies for PI3K pathway inhibitors in non-small-cell
      lung cancer (NSCLC). EXPERIMENTAL DESIGN: Molecular profiling for candidate PI3K
      predictive biomarkers was conducted on a collection of NSCLC tumor samples.
      Assays included comparative genomic hybridization, reverse-transcription
      polymerase chain reaction gene expression, mutation detection for PIK3CA and
      other oncogenes, PTEN immunohistochemistry, and FISH for PIK3CA copy number. In
      addition, a panel of NSCLC cell lines characterized for alterations in the PI3K
      pathway was screened with PI3K and dual PI3K/mTOR inhibitors to assess the
      preclinical predictive value of candidate biomarkers. RESULTS: PIK3CA
      amplification was detected in 37% of squamous tumors and 5% of adenocarcinomas,
      whereas PIK3CA mutations were found in 9% of squamous and 0% of adenocarcinomas.
      Total loss of PTEN immunostaining was found in 21% of squamous tumors and 4% of
      adenocarcinomas. Cell lines harboring pathway alterations (receptor tyrosine
      kinase activation, PI3K mutation or amplification, and PTEN loss) were
      exquisitely sensitive to the PI3K inhibitor GDC-0941. A dual PI3K/mTOR inhibitor
      had broader activity across the cell line panel and in tumor xenografts. The
      combination of GDC-0941 with paclitaxel, erlotinib, or a mitogen-activated
      protein-extracellular signal-regulated kinase inhibitor had greater effects on
      cell viability than PI3K inhibition alone. CONCLUSIONS: Candidate biomarkers for
      PI3K inhibitors have predictive value in preclinical models and show histology
      specific alterations in primary tumors, suggesting that distinct biomarker
      strategies may be required in squamous compared with nonsquamous NSCLC patient
      populations.

PMID- 23136192
TI  - The critical role of dysregulated FOXM1-PLAUR signaling in human colon cancer
      progression and metastasis.
AB  - PURPOSE: The mammalian Forkhead Box (Fox) transcription factor FOXM1 is
      implicated in tumorigenesis including mouse intestinal cancer. However, the
      clinical significance of FOXM1 signaling in human colorectal cancer pathogenesis
      remains unknown. EXPERIMENTAL DESIGN: We investigated FOXM1 expression in 203
      cases of primary colon cancer and matched normal colon tissue specimens and
      explored the underlying mechanisms of altered FOXM1 expression and the impact of
      this altered expression on colon cancer growth and metastasis using in vitro and
      animal models of colon cancer. RESULTS: We found weak expression of FOXM1 protein
      in the colon mucosa, whereas we observed strong FOXM1 expression in tumor-cell
      nuclei of colon cancer and lymph node metastases. A Cox proportional hazards
      model revealed that FOXM1 expression was an independent prognostic factor in
      multivariate analysis. Experimentally, overexpression of FOXM1 by gene transfer
      significantly promoted the growth and metastasis of colon cancer cells in
      orthotopic mouse models, whereas knockdown of FOXM1 expression by siRNA did the
      opposite. Promotion of colon tumorigenesis by FOXM1 directly and significantly
      correlated with activation of urokinase-type plasminogen activator receptor
      (PLAUR) expression and elevation of invasion and metastasis. CONCLUSIONS: Given
      the importance of FOXM1 in regulation of the expression of genes key to cancer
      biology, dysregulated expression and activation of FOXM1 may play important roles
      in colon cancer progression and metastasis.

PMID- 23136193
TI  - Development of [(11)C]erlotinib positron emission tomography for in vivo
      evaluation of EGF receptor mutational status.
AB  - PURPOSE: To evaluate whether, in patients with non-small cell lung carcinoma
      (NSCLC), tumor uptake of [(11)C]erlotinib can be quantified and imaged using
      positron emission tomography and to assess whether the level of tracer uptake
      corresponds with the presence of activating tumor EGF receptor (EGFR) mutations.
      EXPERIMENTAL DESIGN: Ten patients with NSCLCs, five with an EGFR exon 19
      deletion, and five without were scanned twice (test retest) on the same day with
      an interval of at least 4 hours. Each scanning procedure included a low-dose
      computed tomographic scan, a 10-minute dynamic [(15)O]H(2)O scan, and a 1-hour
      dynamic [(11)C]erlotinib scan. Data were analyzed using full tracer kinetic
      modeling. EGFR expression was evaluated using immunohistochemistry. RESULTS: The
      quantitative measure of [(11)C]erlotinib uptake, that is, volume of distribution
      (V(T)), was significantly higher in tumors with activating mutations, that is,
      all with exon 19 deletions (median V(T), 1.76; range, 1.25-2.93), than in those
      without activating mutations (median V(T), 1.06; range, 0.67-1.22) for both test
      and retest data (P = 0.014 and P = 0.009, respectively). Good reproducibility of
      [(11)C]erlotinib V(T) was seen (intraclass correlation coefficient = 0.88).
      Intergroup differences in [(11)C]erlotinib uptake were not correlated with EGFR
      expression levels, nor tumor blood flow. CONCLUSION: [(11)C]erlotinib V(T) was
      significantly higher in NSCLCs tumors with EGFR exon 19 deletions.

PMID- 23136194
TI  - Impact of ischemia and procurement conditions on gene expression in renal cell
      carcinoma.
AB  - PURPOSE: Previous studies have shown that ischemia alters gene expression in
      normal and malignant tissues. There are no studies that evaluated effects of
      ischemia in renal tumors. This study examines the impact of ischemia and tissue
      procurement conditions on RNA integrity and gene expression in renal cell
      carcinoma. EXPERIMENTAL DESIGN: Ten renal tumors were resected without renal
      hilar clamping from 10 patients with renal clear cell carcinoma. Immediately
      after tumor resection, a piece of tumor was snap frozen. Remaining tumor samples
      were stored at 4 degrees C, 22 degrees C, and 37 degrees C and frozen at 5, 30,
      60, 120, and 240 minutes. Histopathologic evaluation was conducted on all tissue
      samples, and only those with greater than 80% tumor were selected for further
      analysis. RNA integrity was confirmed by electropherograms and quantitated using
      RNA integrity number index. Altered gene expression was assessed by paired, two
      sample t test between the zero time point and aliquots from various conditions
      obtained from the same tumor. RESULTS: One hundred and forty microarrays were
      conducted. Some RNA degradation was observed 240 minutes after resection at 37
      degrees C. The expression of more than 4,000 genes was significantly altered by
      ischemia times or storage conditions. The greatest gene expression changes were
      observed with longer ischemia time and warmer tissue procurement conditions.
      CONCLUSION: RNA from kidney cancer remains intact for up to 4 hours post surgical
      resection regardless of storage conditions. Despite excellent RNA preservation,
      time after resection and procurement conditions significantly influence gene
      expression profiles. Meticulous attention to preacquisition variables is of
      paramount importance for accurate tumor profiling.

PMID- 23136195
TI  - Targeted MET inhibition in castration-resistant prostate cancer: a randomized
      phase II study and biomarker analysis with rilotumumab plus mitoxantrone and
      prednisone.
AB  - PURPOSE: To evaluate the efficacy, safety, biomarkers, and pharmacokinetics of
      rilotumumab, a fully human, monoclonal antibody against hepatocyte growth factor
      (HGF)/scatter factor, combined with mitoxantrone and prednisone (MP) in patients
      with castration-resistant prostate cancer (CRPC). EXPERIMENTAL DESIGN: This
      double-blinded phase II study randomized (1:1:1) patients with progressive,
      taxane-refractory CRPC to receive MP (12 mg/m(2) i.v. day 1, 5 mg twice a day
      orally days 1-21, respectively) plus 15 mg/kg rilotumumab, 7.5 mg/kg rilotumumab,
      or placebo (i.v. day 1) every 3 weeks. The primary endpoint was overall survival
      (OS). RESULTS: One hundred and forty-four patients were randomized. Median OS was
      12.2 versus 11.1 months [HR, 1.10; 80% confidence interval (CI), 0.82-1.48] in
      the combined rilotumumab versus control arms. Median progression-free survival
      was 3.0 versus 2.9 months (HR, 1.02; 80% CI, 0.79-1.31). Treatment appeared well
      tolerated with peripheral edema (24% vs. 8%) being more common with rilotumumab.
      A trend toward unfavorable OS was observed in patients with high tumor MET
      expression regardless of treatment. Soluble MET levels increased in all treatment
      arms. Total HGF levels increased in the rilotumumab arms. Rilotumumab showed
      linear pharmacokinetics when co-administered with MP. CONCLUSIONS: Rilotumumab
      plus MP had manageable toxicities and showed no efficacy improvements in this
      estimation study. High tumor MET expression may identify patients with CRPC with
      poorer prognosis.

PMID- 23136196
TI  - A multicenter, phase I, dose-escalation study to assess the safety, tolerability,
      and pharmacokinetics of etirinotecan pegol in patients with refractory solid
      tumors.
AB  - PURPOSE: This study was designed to establish the maximum tolerated dose (MTD)
      and to evaluate tolerability, pharmacokinetics, and antitumor activity of
      etirinotecan pegol. EXPERIMENTAL DESIGN: Patients with refractory solid
      malignancies were enrolled and assigned to escalating-dose cohorts. Patients
      received 1 infusion of etirinotecan pegol weekly 3 times every 4 weeks (w *
      3q4w), or every 14 days (q14d), or every 21 days (q21d), with MTD as the primary
      end point using a standard 3 + 3 design. RESULTS: Seventy-six patients were
      entered onto 3 dosing schedules (58-245 mg/m(2)). The MTD was 115 mg/m(2) for the
      w * 3q4w schedule and 145 mg/m(2) for both the q14d and q21d schedules. Most
      adverse events related to study drug were gastrointestinal disorders and were
      more frequent at higher doses of etirinotecan pegol. Late onset diarrhea was
      observed in some patients, the frequency of which generally correlated with dose
      density. Cholinergic diarrhea commonly seen with irinotecan treatment did not
      occur in patients treated with etirinotecan pegol. Etirinotecan pegol
      administration resulted in sustained and controlled systemic exposure to SN-38,
      which had a mean half-life of approximately 50 days. Overall, the
      pharmacokinetics of etirinotecan pegol are predictable and do not require complex
      dosing adjustments. Confirmed partial responses were observed in 8 patients with
      breast, colon, lung (small and squamous cell), bladder, cervical, and
      neuroendocrine cancer. CONCLUSION: Etirinotecan pegol showed substantial
      antitumor activity in patients with various solid tumors and a somewhat different
      safety profile compared with the irinotecan historical profile. The MTD
      recommended for phase II clinical trials is 145 mg/m(2) q14d or q21d.

PMID- 23136197
TI  - Predictive biomarkers of sensitivity to the aurora and angiogenic kinase
      inhibitor ENMD-2076 in preclinical breast cancer models.
AB  - PURPOSE: The Aurora kinases are a family of conserved serine-threonine kinases
      with key roles in mitotic cell division. As with other promising anticancer
      targets, patient selection strategies to identify a responsive subtype will
      likely be required for successful clinical development of Aurora kinase
      inhibitors. The purpose of this study was to evaluate the antitumor activity of
      the Aurora and angiogenic kinase inhibitor ENMD-2076 against preclinical models
      of breast cancer with identification of candidate predictive biomarkers.
      EXPERIMENTAL DESIGN: Twenty-nine breast cancer cell lines were exposed to ENMD
      2076 and the effects on proliferation, apoptosis, and cell-cycle distribution
      were evaluated. In vitro activity was confirmed in MDA-MB-468 and MDA-MB-231
      triple-negative breast cancer xenografts. Systematic gene expression analysis was
      used to identify up- and downregulated pathways in the sensitive and resistant
      cell lines, including within the triple-negative breast cancer subset. RESULTS:
      ENMD-2076 showed antiproliferative activity against breast cancer cell lines,
      with more robust activity against cell lines lacking estrogen receptor expression
      and those without increased HER2 expression. Within the triple-negative breast
      cancer subset, cell lines with a p53 mutation and increased p53 expression were
      more sensitive to the cytotoxic and proapoptotic effects of ENMD-2076 exposure
      than cell lines with decreased p53 expression. CONCLUSIONS: ENMD-2076 exhibited
      robust anticancer activity against models of triple-negative breast cancer and
      the candidate predictive biomarkers identified in this study may be useful in
      selecting patients for Aurora kinase inhibitors in the future.

PMID- 23136198
TI  - Ex vivo enzymatic treatment of aged CD4 T cells restores cognate T cell helper
      function and enhances antibody production in mice.
AB  - Previous in vitro studies showed that CD4 T cells from old mice have defects in
      TCR signaling, immune synapse formation, activation, and proliferation. We
      reported that removing a specific set of surface glycoproteins by ex vivo
      treatment with O-sialoglycoprotein endopeptidase (OSGE) can reverse many aspects
      of the age-related decline in CD4 T cell function. However, the specific
      mechanism by which this process occurs remains unclear, and it is unknown whether
      this enzymatic treatment can also restore important aspects of adaptive immunity
      in vivo. By using an in vivo model of the immune response based on adoptive
      transfer of CD4 T cells from pigeon cytochrome C-specific transgenic H-2(k/k) TCR
      Valpha(11)Vbeta(3) CD4(+) mice to syngeneic hosts, we demonstrate that aging
      diminishes CD28 costimulatory signals in CD4 T cells. These age-associated
      defects include changes in phosphorylation of AKT and expression of glucose
      transporter type I, inducible T cell costimulatory molecule, and CD40L,
      suggesting that the lack of CD28 costimulation contributes to age-dependent loss
      of CD4 function. All of these deficits can be reversed by ex vivo OSGE treatment.
      Blocking B7-CD28 interactions on T cells prevents OSGE-mediated restoration of T
      cell function, suggesting that changes in surface glycosylation, including CD28,
      may be responsible for the age-related costimulation decline. Finally, we show
      that the age-related decline in CD4 cognate helper function for IgG production
      and long-term humoral immunity can also be restored by OSGE treatment of CD4 T
      cells prior to adoptive transfer.

PMID- 23136199
TI  - Lymphopenia-driven homeostatic regulation of naive T cells in elderly and
      thymectomized young adults.
AB  - Reduced thymopoiesis and continuous mobilization of naive T cells into the
      effector-memory pool can lead to severe alterations of the naive T cell
      compartment. However, maintenance of the naive T cell population is essential to
      mount effective immune responses. Evidence of homeostatic regulation of naive T
      cells is currently debated in animal models. In humans, the situation remains
      unresolved, in particular with advanced age. In this study, we analyzed the
      CD4(+) and CD8(+) naive T cell compartments from elderly, young adults
      thymectomized during early childhood, and HIV-1-infected patients, which are
      characterized by T lymphocytopenia. We show a direct association between
      increased turnover and decreased frequency of naive T cells. Moreover, the IL-7
      induced pathway was fully functional in naive T cells from elderly and young
      adults thymectomized during early childhood, who are characterized by elevated IL
      7 plasma levels. Our findings support the establishment of homeostatic regulation
      of naive T cell proliferation in humans. This regulation is particularly active
      in lymphopenic hosts, such as elderly and thymectomized patients.

PMID- 23136200
TI  - Nonalloreactive T cells prevent donor lymphocyte infusion-induced graft-versus
      host disease by controlling microbial stimuli.
AB  - In mice, graft-versus-host reactions, associated with powerful graft-versus-tumor
      effects, can be achieved without graft-versus-host disease (GVHD) by delayed
      administration of donor lymphocyte infusions (DLI) to established mixed chimeras.
      However, GVHD sometimes occurs after DLI in established mixed chimeric patients.
      In contrast to mice, in which T cell recovery from the thymus occurs prior to DLI
      administration, human T cell reconstitution following T cell-depleted
      hematopoietic cell transplantation is slow, resulting in lymphopenia at the time
      of DLI. We demonstrate in this study that T cell lymphopenia is an independent
      risk factor for GVHD following DLI in the absence of known inflammatory stimuli.
      DLI-induced GVHD was prevented in lymphopenic recipients by prior administration
      of a small number of nonalloreactive polyclonal T cells, insufficient to prevent
      lymphopenia-associated expansion of subsequently administered T cells, through a
      regulatory T cell-independent mechanism. GVHD was not inhibited by T cells with
      irrelevant specificity. Moreover, administration of antibiotics reduced the
      severity of GVHD in lymphopenic hosts. Accumulation of DLI-derived effector T
      cells and host hematopoietic cell elimination were markedly diminished by
      regulatory T cell-depleted, nonalloreactive T cells. Finally, thymectomized mixed
      chimeras showed increased GVHD following delayed DLI. Collectively, our data
      demonstrate that in the absence of known conditioning-induced inflammatory
      stimuli, T cell lymphopenia is a risk factor for GVHD in mixed chimeras receiving
      delayed DLI. Our data suggest that the predisposition to GVHD can at least in
      part be explained by the presence of occult inflammatory stimuli due to the
      absence of T cells to control microbial infections.

PMID- 23136201
TI  - Cyclin-dependent kinase 2 controls peripheral immune tolerance.
AB  - Adaptive immunity requires signals from both the TCR and the costimulatory
      molecule CD28. These receptors activate multiple signaling pathways, including
      the cyclin-dependent kinase (CDK) cascade, and antigenic signals in the absence
      of costimulation result in a tolerant state that is enforced by the CDK
      inhibitory protein p27kip1. We find that CDK2, the major target of p27kip1, is
      highly active in T cells that infiltrate and reject cardiac allografts. We used
      mice genetically deficient for CDK2 to determine whether CDK2 is required for T
      cell alloimmunity. Blockade of CD28 costimulation alone was unable to inhibit the
      rejection of cardiac allografts by wild-type recipients. However, targeting this
      pathway in CDK2-deficient recipients led to long-term allograft survival. CDK2
      deficient CD4(+) T cells proliferated normally in response to stimulation in
      vitro and in vivo, however, genetic, short hairpin RNA, or small molecule
      mediated antagonism of CDK2 resulted in decreased production of IL-2 and IFN
      gamma. In addition, surviving grafts from CDK2-deficient recipients showed
      increased infiltration of Foxp3(+) regulatory T cells (Treg), and Treg from CDK2
      deficient mice exhibited increased suppressive activity in vitro and in an in
      vivo model of inflammatory bowel disease. These data suggest that p27kip1
      promotes peripheral tolerance through its ability to inhibit CDK2, which
      otherwise acts to promote conventional T cell differentiation and restrict Treg
      function.

PMID- 23136202
TI  - beta-glucan curdlan induces IL-10-producing CD4+ T cells and inhibits allergic
      airway inflammation.
AB  - A number of studies have suggested a correlation between a decreased incidence in
      infectious diseases and an increased incidence of allergic diseases, including
      asthma. Although several pathogen-derived products have been shown to possess
      therapeutic potential for allergic diseases, it remains largely unknown whether
      beta-glucan, a cell wall component of a variety of fungi, yeasts, and bacteria,
      has a regulatory potential for allergic diseases. In this study, we examined the
      effect of curdlan, a linear beta-(1-3)-glucan, on the development of allergic
      airway inflammation. We found that i.p. injection of curdlan significantly
      inhibited Ag-induced eosinophil recruitment and Th2 cytokine production in the
      airways. The activation of CD4(+) T cells in the presence of curdlan induced IL
      10-producing CD4(+) T cells with high levels of c-Maf expression. Curdlan-induced
      development of IL-10-producing CD4(+) T cells required the presence of APCs and
      ICOS/ICOS ligand interaction. Curdlan-induced development of IL-10-producing
      CD4(+) T cells also required intrinsic expression of STAT6. Furthermore, the
      transfer of Ag-specific CD4(+) T cells that were stimulated in the presence of
      curdlan inhibited Ag-induced eosinophil recruitment into the airways. Taken
      together, these results suggest that curdlan is capable of inducing IL-10
      producing CD4(+) T cells and inhibiting the development of eosinohilic airway
      inflammation, underscoring the therapeutic potential of curdlan for allergic
      diseases.

PMID- 23136203
TI  - Suppression of vaccine immunity by inflammatory monocytes.
AB  - Vaccine adjuvant-induced inflammation augments vaccine immunity in part by
      recruiting APCs to vaccine draining lymph nodes (LNs). However, the role of one
      APC subtype, inflammatory monocytes, in regulating vaccine immunity in healthy
      animals has not been fully examined in detail. Therefore, vaccine-mediated
      monocyte recruitment and subsequent immune responses were investigated using
      murine vaccination models and in vitro assays. Recruitment of inflammatory
      monocytes to vaccine draining LNs was rapid and mediated primarily by local
      production of MCP-1, as revealed by studies in MCP-1(-/-) mice. Interrupting
      monocyte recruitment to LNs by either transient monocyte depletion or monocyte
      migration blockade led to marked amplification of both cellular and humoral
      immune responses to vaccination. These results were most consistent with the idea
      that rapidly mobilized inflammatory monocytes were actually suppressing vaccine
      responses. The suppressive nature of vaccine-elicited monocytes was confirmed
      using in vitro cocultures of murine monocytes and T cells. Furthermore, it was
      determined that inflammatory monocytes suppressed T cell responses by
      sequestering cysteine, as cysteine supplementation in vitro and in vivo
      appreciably augmented vaccine responses. These findings indicated, therefore,
      that vaccination-elicited inflammation, although necessary for effective
      immunity, also generated potent counter-regulatory immune responses that were
      mediated primarily by inflammatory monocytes. Therefore, interrupting monocyte
      mediated vaccine counterregulatory responses may serve as an effective new
      strategy for broadly amplifying vaccine immunity.

PMID- 23136206
TI  - Is higher choroid plexus 'load' an aetiologic factor in idiopathic intracranial
      hypertension? A clinico-imaging morphometric correlative study.
AB  - BACKGROUND: Idiopathic intracranial hypertension (IIH) is a condition of raised
      cerebrospinal fluid (CSF) pressure with normal ventricular size. Although the
      pathogenesis of IIH remains controversial, increased CSF formation may be
      important. We hypothesised that if increased CSF formation was an aetiologic
      factor, it might result in a macroscopic increase in size of the choroid plexus
      (CP). METHOD: We retrospectively studied 50 patients with IIH. Total size of the
      CP was estimated on computed tomography (CT) venograms from the sum of axial
      areas measured at three locations. Results were compared with the CP load of 50
      matched controls on post-contrast head CTs. Evans Index was measured to exclude
      ventriculomegaly. Results were analysed using a Student's t test for independent
      samples (p < 0.05), and the effect of ICP was tested on the dependent variable
      (area of CP) using regression analysis. RESULTS: There was no significant
      difference in the size of the CP glomus, total axial areas of the CP between IIH
      patients (183 mm(2)) and controls (178 mm(2)) and no correlation between the
      'load' of CP and the degree of intracranial pressure (ICP) (R (2)< 0.02).
      CONCLUSION: If increased CSF formation is an aetiologic factor in IIH, this is
      not reflected in a corresponding raised 'load' of CP.

PMID- 23136205
TI  - IPS-1 signaling has a nonredundant role in mediating antiviral responses and the
      clearance of respiratory syncytial virus.
AB  - The cytosolic RNA helicases melanoma differentiation-associated gene 5 and
      retinoic acid-inducible gene-I and their adaptor IFN-beta promoter stimulator
      (IPS-1) have been implicated in the recognition of viral RNA and the production
      of type I IFN. Complementing the endosomal TLR, melanoma differentiation
      associated gene 5, and retinoic acid-inducible gene-I provides alternative
      mechanisms for viral detection in cells with reduced phagocytosis or autophagy.
      The infection route of respiratory syncytial virus (RSV)-via fusion of virus
      particles with the cell membrane-points to IPS-1 signaling as the pathway of
      choice for downstream antiviral responses. In the current study, viral clearance
      and inflammation resolution were indeed strongly affected by the absence of an
      initial IPS-1-mediated IFN-beta response. Despite the blunted inflammatory
      response in IPS-1-deficient alveolar epithelial cells, pulmonary macrophages, and
      CD11b(+) dendritic cells (DC), the lungs of RSV-infected IPS-1-knockout mice
      showed augmented recruitment of inflammatory neutrophils, monocytes, and DC.
      Interestingly, pulmonary CD103(+) DC could functionally compensate for IPS-1
      deficiency with the upregulation of certain inflammatory cytokines and
      chemokines, possibly via TLR3 and TLR7 signaling. The increased inflammation and
      reduced viral clearance in IPS-1-knockout mice was accompanied by increased T
      cell activation and IFN-gamma production. Experiments with bone marrow chimeras
      indicated that RSV-induced lung pathology was most severe when IPS-1 expression
      was lacking in both immune and nonimmune cell populations. Similarly, viral
      clearance was rescued upon restored IPS-1 signaling in either the nonimmune or
      the immune compartment. These data support a nonredundant function for IPS-1 in
      controlling RSV-induced inflammation and viral replication.

PMID- 23136204
TI  - CD8+ T cell-derived IFN-gamma prevents infection by a second heterologous virus.
AB  - Persistent viral infection is often associated with dysfunctional immune
      responses against unrelated pathogens. Lymphocytic choriomeningitis virus (LCMV)
      can establish acute or chronic infections in mice and is widely used as a model
      for persistent virus infections in humans. Mice infected with LCMV develop a
      transient defect in Ag-specific immunity against heterologous viral infection.
      Although it has been proposed that LCMV infection induces an immunosuppressed
      state within the host, our data show that infected mice successfully clear
      vaccinia virus through a mechanism that involves CD8(+) T cell-derived IFN-gamma.
      This observation demonstrates that chronic LCMV infection does not impair
      protective immunity against heterologous viral challenge. Rather, a natural
      sterilizing immunity is induced following a primary infection that prevents a
      secondary infection. Our findings suggest a need to re-evaluate current thoughts
      about the immune suppression that might occur during a persistent infection.

PMID- 23136207
TI  - Change in intraindividual ICHD-II headache diagnosis over time: a follow-up of
      the DMKG headache study.
AB  - BACKGROUND: Change in headache diagnoses over time within the same individual is
      not well studied in the adult population. In this study, we prospectively
      examined the individual variation of migraine and tension-type headache (TTH)
      diagnoses over time. METHODS: As part of the epidemiological Deutsche Migrane und
      Kopfschmerzgesellschaft (DMKG) headache study, 1312 participants were personally
      interviewed and 1122 responded to a second mailed questionnaire 2.2 years later.
      Headaches were assigned to migraine or TTH at two different points in time using
      the International Headache Classification, ICHD-II. We used broad (definite and
      probable subtypes) and strict (only definite type) definitions of migraine and
      TTH. RESULTS: Using the broad definition increased the reproducibility of
      migraine diagnosis from 48.0% to 62.0% and of TTH from 59.0% to 65.0%. A constant
      TTH diagnosis was related to a higher social status (OR 2.81; 95% CI 1.43-5.53) a
      higher level of education (OR 1.96; 95% CI 1.00-3.85) and physical inactivity (OR
      2.28; 95% CI 1.16-4.49). A constant diagnosis of definite migraine was associated
      with severe headache (OR 2.64; 95% CI 0.97-7.21) and frequent use of headache
      medication (OR 4.73; 95% CI 0.95-23.60). The result that coexisting TTH decreased
      the likelihood of a constant migraine (OR 0.29; 95% CI 0.10-0.85) is assumed to
      indicate response variability. CONCLUSIONS: In epidemiological studies, definite
      and probable subtypes should be included in the diagnosis to increase the
      diagnostic accuracy.

PMID- 23136208
TI  - Migraine tweets - what can online behavior tell us about disease?

PMID- 23136209
TI  - Oxygen treatment is effective in migraine with autonomic symptoms.
AB  - INTRODUCTION: While inhalation of high-flow 100% oxygen is highly effective in
      cluster headache, studies on its efficacy in migraine are sparse and
      controversial. CASE: We report the case of a 22-year-old patient with an eight
      year history of strictly unilateral migraine without aura but cranial autonomic
      symptoms. She repeatedly responded completely to inhalation of high-flow pure
      oxygen within 15 min but suffered from recurrence of attacks within 30 min after
      discontinuation. DISCUSSION: In line with experimental animal studies, this case
      suggests a clinically relevant efficacy of inhaled oxygen in patients with
      migraine with accompanying cranial autonomic symptoms.

PMID- 23136210
TI  - Child neglect and the development of externalizing behavior problems:
      associations with maternal drug dependence and neighborhood crime.
AB  - Given the high prevalence of child neglect among maltreatment subtypes, and its
      association with exposure to additional environmental adversity, understanding
      the processes that potentiate child neglect and link neglect to subsequent child
      externalizing psychopathology may shed light on key targets for preventive
      intervention. Among 170 urban low-income children (ages 4-9) and their mothers,
      this 5-year prospective study examined the effects of early neglect severity and
      maternal substance abuse, as well as neighborhood crime, on children's later
      externalizing behavior problems. Severity of child neglect (up to age 6 years)
      mediated the relation between maternal drug dependence diagnosis (MDDD),
      determined at children's age of 4 years, and children's externalizing behavior
      problems at age 9. Rates of neighborhood crime mediated the link between presence
      of child neglect and children's externalizing behavior problems. The roles of
      MDDD, child neglect, and community violence in the development of child
      psychopathology are discussed in terms of their implications for intervention.

PMID- 23136211
TI  - Control of mineral metabolism and bone disease in haemodialysis patients: which
      optimal targets?
AB  - BACKGROUND: There is a high drug treatment burden on patients receiving long-term
      dialysis therapy. Abnormalities of calcium and phosphate metabolism are
      associated with increased mortality, and attempts to correct these disturbances
      may improve survival. METHODS: We prospectively evaluated the targets of the
      currently used Kidney Disease: Improving Global Outcomes (KDIGO) guidelines in
      8377 prevalent patients receiving intermittent haemodialysis therapy in France
      from July 2007 to December 2009. RESULTS: Adjusted Cox analyses showed that only
      one among six targets was predictive of mortality, i.e. a serum intact
      parathyroid hormone (iPTH) <130 pg/mL. A continuous risk analysis using
      fractional polynomials showed a 10% increase in hazard ratio (HR) for mortality
      for a serum phosphate <0.71 (2.2) and >1.98 (6.14) mmol/L (mg/dL), a non
      corrected serum calcium <1.59 (6.37) and >2.41 (9.66) mmol/L (mg/dL) and a serum
      iPTH <100 and >1090 pg/mL. CONCLUSION: The findings of our observational study
      confirm the existence of a grey zone, in which precise biochemical targets are
      difficult to define, with the exception of avoiding extreme values. Given the
      absence of intervention trials proving the clinical usefulness of phosphorus
      control, and pending the results of large clinical trials on the effect of
      optimal PTH and calcium control on hard outcomes, the present findings may help
      to refine future recommendations for the treatment of chronic haemodialysis
      patients.

PMID- 23136212
TI  - Angiopoietin-2 in sepsis: lost in translation?

PMID- 23136213
TI  - Experimental evidence of cell dissemination playing a role in pathogenesis of IgA
      nephropathy in multiple lymphoid organs.
AB  - BACKGROUND: Since the pathogenesis of immunoglobulin A (IgA) nephropathy (IgAN)
      remains unclear, the rationale for current IgAN therapies is still obscure.
      Recent studies have shown that galactose-deficient IgA1 (GdIgA1) plays a critical
      role in the pathogenesis of IgAN and can be a non-invasive IgAN biomarker,
      although the origin of the pathogenic cells producing GdIgA1 is unknown. We
      examined the cell types and localization of pathogenic cells in IgAN-prone mice.
      METHODS: We transplanted bone marrow (BM) or spleen cells with or without
      specific cell types from IgAN-prone mice, which have many features similar to
      human IgAN, to identify cell types responsible for the IgAN phenotype and to
      determine their localization. RESULTS: BM transplantation and whole spleen cell
      transfer from IgAN-prone mice reconstituted IgAN in normal and severe combined
      immunodeficiency mice. Depletion of CD90(+) spleen cells had no affect on
      reconstitution, whereas CD19(+) B cells from the spleen were sufficient to
      reconstitute IgAN in both recipients. CONCLUSIONS: These results indicate that
      CD19(+) B cells, which can regulate nephritogenic IgA production in a T-cell
      independent manner, are responsible for the disease and are disseminated in
      peripheral lymphoid organs.

PMID- 23136214
TI  - Multipass haemodialysis: a novel dialysis modality.
AB  - INTRODUCTION: Most home haemodialysis (HD) modalities are limited to home use
      since they are based on a single-pass (SP) technique, which requires preparation
      of large amounts of dialysate. We present a new dialysis method, which requires
      minimal dialysate volumes, continuously recycled during treatment [multipass HD
      (MPHD)]. Theoretical calculations suggest that MPHD performed six times weekly
      for 8 h/night, using a dialysate bath containing 50% of the calculated body
      water, will achieve urea clearances equivalent to conventional HD 4 h thrice
      weekly, and a substantial clearance of higher middle molecules. METHODS: Ten
      stable HD patients were dialyzed for 4 h using standard SPHD (dialysate flow 500
      mL/min). Used dialysate was collected. One week later, an 8-h MPHD was performed.
      The dialysate volume was 50% of the calculated water volume, the dialysate inflow
      500 mL/min-0.5 * ultrafiltration/min and the outflow 500 mL/min + 0.5 *
      ultrafiltration/min. Elimination rates of urea, creatinine, uric acid, phosphate
      and beta2-microglobulin (B2M) and dialysate saturation were determined hourly.
      RESULTS: Three hours of MPHD removed 49, 54, 50, 51 and 57%, respectively, of the
      amounts of urea, creatinine, uric acid, phosphate and B2M that were removed by 4
      h conventional HD. The corresponding figures after 8 h MPHD were 63, 78, 74, 78
      and 111%. CONCLUSIONS: Clearance of small molecules using MPHD 6 * 8 h/week will
      exceed traditional HD 3 * 4 h/week. Similarly, clearance of large molecules will
      significantly exceed traditional HD and HD 5 * 2.5 h/week. This modality will
      increase patients' freedom of movement compared with traditional home HD. The new
      method can also be used in the intensive care unit and for automated peritoneal
      dialysis.

PMID- 23136215
TI  - Pneumatic compression devices during hemodialysis: a randomized crossover trial.
AB  - BACKGROUND: Maintenance of central blood volume (CBV) is essential for
      hemodynamic stability during hemodialysis (HD), though preservation of CBV is
      poorly understood. Pneumatic compression devices (PCDs) during HD may help
      maintain CBV. METHODS: We performed a randomized, crossover trial to determine
      the effect of PCDs on CBV during HD. Patients underwent two consecutive mid-week
      HD sessions, randomized to begin the first session either with or without PCDs
      [stratified by intradialytic hypotension (IDH)-prone status]. The primary outcome
      was change in CBV during HD. The secondary outcomes were change in other
      hemodynamic and volume status parameters. RESULTS: Fifty-one patients (median age
      65 years, 75% male, 22% IDH-prone) were randomized; forty-six completed the
      study. During HD, the median change in CBV for PCD and control sessions was -0.08
      versus -0.05 L (P = 0.62). There was no difference in the change in cardiac
      output (CO) (-0.63 versus -0.49 L/min, P = 0.78) or systemic vascular resistance
      (SVR) (+1.30 versus +1.55 mmHg/L/min, P = 0.67) for PCDs versus control. Based on
      the bioimpedance measurements, patients were not volume overloaded pre-dialysis.
      There was a greater reduction in total body water (TBW) (-2.6 versus -2.3 L, P =
      0.05) and intracellular fluid (ICF) volume (-1.3 versus -1.1 L, P = 0.03), and no
      difference in change in the extracellular fluid (ECF) volume (1.3 versus 1.2 L, P
      = 0.09) with PCDs versus control. Similar results were observed in IDH-prone
      patients. CONCLUSIONS: Compared with standard of care, PCDs have no effect on
      intradialytic hemodynamic parameters, including CBV, although they may allow
      greater capacity for fluid removal. Further studies are required to better
      understand physiological and hemodynamic changes in patients during HD.

PMID- 23136216
TI  - Renal function and survival in 200 patients undergoing ECMO therapy.
AB  - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is increasingly used in
      the intensive care unit (ICU) setting to improve gas exchange in patients with
      acute respiratory distress syndrome as well as in patients pre- and post-heart
      and lung transplantation. In this clinical setting, acute kidney injury (AKI) is
      frequently observed. So far, it is unknown how AKI affects the survival of
      critically ill patients receiving ECMO support and whether veno-veno and veno
      arterial ECMO have different effects on kidney function. METHODS: This is a
      retrospective analysis of patients undergoing ECMO treatment in medical and
      surgical ICUs in a tertiary care centre. We evaluated all patients undergoing
      ECMO treatment at our centre between 1 January 2005 and 31 December 2010. Data
      from all 200 patients (83F/117M), median age 45 (17-83) years, were obtained by
      chart review. Follow-up data were obtained for up to 3 months. RESULTS: Three
      month survival of all patients was 31%. Of the 200 patients undergoing ECMO
      treatment, 60% (120/200) required renal replacement therapy (RRT) for AKI. While
      patients without RRT showed a 3-month survival of 53%, the survival of patients
      with AKI requiring RRT was 17% (P = 0.001). Longer duration of RRT was associated
      with a higher mortality. CONCLUSIONS: AKI requiring RRT therapy in patients
      undergoing ECMO treatment increases mortality in ICU patients. Future studies
      have to clarify whether it is possible to identify patients who benefit from the
      combination of ECMO and RRT.

PMID- 23136217
TI  - Relationship of pharyngeal water content and jugular volume with severity of
      obstructive sleep apnea in renal failure.
AB  - BACKGROUND: In patients with end-stage renal disease (ESRD), fluid overload may
      contribute to their high prevalence of obstructive sleep apnea (OSA) by
      increasing the amount of fluid displaced from the legs into the neck overnight,
      and possibly compressing the upper airway (UA). Indeed, in ESRD patients, the
      amount of overnight rostral fluid displacement from the legs is related to the
      frequency of apneas and hypopneas per hour of sleep (apnea-hypopnea index, AHI).
      We, therefore, hypothesized that in ESRD patients, the greater the UA-mucosal
      water content (UA-MWC) and internal jugular vein volume (IJVVol), the higher the
      AHI. METHODS: We studied 20 patients with ESRD on thrice weekly hemodialysis who
      had undergone diagnostic polysomnography (age 41.0 +/- 12.3 years, with a body
      mass index (BMI) of 25.8 +/- 6.3 kg/m(2) and an AHI of 20.2 +/- 26.8). The leg
      fluid volume (LFV) was measured by bioelectric impedance. The IJVVol and MWC were
      measured by UA magnetic resonance imaging (MRI). RESULTS: The only significant
      independent correlates of the AHI were IJVVol (r = 0.801, P < 0.0001) and UA-MWC
      (r = 0.720, P = 0.0005) which together explained 72% of its variability.
      CONCLUSIONS: These data suggest that fluid overload via increased IJVVol, and UA
      MWC, contributes to the pathogenesis of OSA in patients with ESRD. These findings
      help us to explain the high prevalence of OSA in ESRD patients, and attenuation
      of OSA in association with nocturnal dialysis. They also suggest the need for
      randomized trials to determine whether more aggressive fluid removal in ESRD
      patients will alleviate OSA.

PMID- 23136218
TI  - Cisplatin-induced injury of the renal distal convoluted tubule is associated with
      hypomagnesaemia in mice.
AB  - BACKGROUND: Cisplatin is an effective anti-neoplastic drug, but its clinical use
      is limited due to dose-dependent nephrotoxicity. The majority of cisplatin
      treated patients develop hypomagnesaemia, often associated with a reduced
      glomerular filtration rate (GFR), polyuria and other electrolyte disturbances.
      The aim of this study is to unravel the molecular mechanism responsible for these
      particular electrolyte disturbances. METHODS: Two groups of 10 mice were injected
      intraperitoneally three times, once every 4 days, with cisplatin (5 mg/kg body
      weight,) or vehicle. Serum and urine electrolyte concentrations were determined.
      Next, renal mRNA levels of distal convoluted tubule (DCT) genes epithelial Mg(2+)
      channel TRPM6, the Na(+)-Cl(-) cotransporter (NCC), and parvalbumin (PV), as well
      as marker genes for other tubular segments were measured by real-time qPCR.
      Subsequently, renal protein levels of NCC, PV, aquaporin 1 and aquaporin 2 were
      determined using immunoblotting and immunohistochemistry (IHC). RESULTS: The
      cisplatin-treated mice developed significant polyuria (2.5 +/- 0.3 and 0.9 +/-
      0.1 mL/24 h, cisplatin versus control, P < 0.05), reduced creatinine clearance
      rate (CCr) (0.18 +/- 0.02 and 0.26 +/- 0.02 mL/min, cisplatin versus control, P <
      0.05) and a substantially reduced serum level of Mg(2+) (1.23 +/- 0.03 and 1.58
      +/- 0.03 mmol/L, cisplatin versus control, P < 0.05), whereas serum Ca(2+), Na(+)
      and K(+) values were not altered. Measurements of 24 h urinary excretion
      demonstrated markedly increased Mg(2+), Ca(2+), Na(+) and K(+) levels in the
      cisplatin-treated group, whereas Pi levels were not changed. The mRNA levels of
      TRPM6, NCC and PV were significantly reduced in the cisplatin group. The
      expression levels of the marker genes for other tubular segments were unaltered,
      except for claudin-16, which was significantly up-regulated by the cisplatin
      treatment. The observed DCT-specific down-regulation was confirmed at the protein
      level. CONCLUSIONS: The present study identified the DCT as an important
      cisplatin-affected renal segment, explaining the high prevalence of
      hypomagnesaemia following treatment.

PMID- 23136219
TI  - Microvascular dysfunction in severe Plasmodium falciparum Malaria.

PMID- 23136220
TI  - Reply to Cunnington et al.

PMID- 23136221
TI  - Whole genome pyrosequencing of rare hepatitis C virus genotypes enhances subtype
      classification and identification of naturally occurring drug resistance
      variants.
AB  - BACKGROUND:  Infection with hepatitis C virus (HCV) is a burgeoning worldwide
      public health problem, with 170 million infected individuals and an estimated 20
      million deaths in the coming decades. While 6 main genotypes generally
      distinguish the global geographic diversity of HCV, a multitude of closely
      related subtypes within these genotypes are poorly defined and may influence
      clinical outcome and treatment options. Unfortunately, the paucity of genetic
      data from many of these subtypes makes time-consuming primer walking the limiting
      step for sequencing understudied subtypes. METHODS:  Here we combined long-range
      polymerase chain reaction amplification with pyrosequencing for a rapid approach
      to generate the complete viral coding region of 31 samples representing poorly
      defined HCV subtypes. RESULTS:  Phylogenetic classification based on full genome
      sequences validated previously identified HCV subtypes, identified a recombinant
      sequence, and identified a new distinct subtype of genotype 4. Unlike
      conventional sequencing methods, use of deep sequencing also facilitated
      characterization of minor drug resistance variants within these uncommon or, in
      some cases, previously uncharacterized HCV subtypes. CONCLUSIONS:  These data aid
      in the classification of uncommon HCV subtypes while also providing a high
      resolution view of viral diversity within infected patients, which may be
      relevant to the development of therapeutic regimens to minimize drug resistance.

PMID- 23136222
TI  - Defining falciparum-malaria-attributable severe febrile illness in moderate-to
      high transmission settings on the basis of plasma PfHRP2 concentration.
AB  - BACKGROUND: In malaria-endemic settings, asymptomatic parasitemia complicates the
      diagnosis of malaria. Histidine-rich protein 2 (HRP2) is produced by Plasmodium
      falciparum, and its plasma concentration reflects the total body parasite burden.
      We aimed to define the malaria-attributable fraction of severe febrile illness,
      using the distributions of plasma P. falciparum HRP2 (PfHRP2) concentrations from
      parasitemic children with different clinical presentations. METHODS: Plasma
      samples were collected from and peripheral blood slides prepared for 1435
      children aged 6-60 months in communities and a nearby hospital in northeastern
      Tanzania. The study population included children with severe or uncomplicated
      malaria, asymptomatic carriers, and healthy control subjects who had negative
      results of rapid diagnostic tests. The distributions of plasma PfHRP2
      concentrations among the different groups were used to model severe malaria
      attributable disease. RESULTS: The plasma PfHRP2 concentration showed a close
      correlation with the severity of infection. PfHRP2 concentrations of >1000 ng/mL
      denoted a malaria-attributable fraction of severe disease of 99% (95% credible
      interval [CI], 96%-100%), with a sensitivity of 74% (95% CI, 72%-77%), whereas a
      concentration of <200 ng/mL denoted severe febrile illness of an alternative
      diagnosis in >10% (95% CI, 3%-27%) of patients. Bacteremia was more common among
      patients in the lowest and highest PfHRP2 concentration quintiles. CONCLUSIONS:
      The plasma PfHRP2 concentration defines malaria-attributable disease and
      distinguishes severe malaria from coincidental parasitemia in African children in
      a moderate-to-high transmission setting.

PMID- 23136223
TI  - Standards of care for treatment of recurrent glioblastoma--are we there yet?
AB  - Newly diagnosed glioblastoma is now commonly treated with surgery, if feasible,
      or biopsy, followed by radiation plus concomitant and adjuvant temozolomide. The
      treatment of recurrent glioblastoma continues to be a moving target as new
      therapeutic principles enrich the standards of care for newly diagnosed disease.
      We reviewed PubMed and American Society of Clinical Oncology abstracts from
      January 2006 to January 2012 to identify clinical trials investigating the
      treatment of recurrent or progressive glioblastoma with nitrosoureas,
      temozolomide, bevacizumab, and/or combinations of these agents. At recurrence, a
      minority of patients are eligible for second surgery or reirradiation, based on
      appropriate patient selection. In temozolomide-pretreated patients, progression
      free survival rates at 6 months of 20%-30% may be achieved either with
      nitrosoureas, temozolomide in various dosing regimens, or bevacizumab.
      Combination regimens among these agents or with other drugs have not produced
      evidence for superior activity but commonly produce more toxicity. More research
      is needed to better define patient profiles that predict benefit from the limited
      therapeutic options available after the current standard of care has failed.

PMID- 23136224
TI  - Prognostic significance of metabolic response by positron emission tomography
      after neoadjuvant chemotherapy for resectable malignant pleural mesothelioma.
AB  - BACKGROUND: To select optimal candidates for extrapleural pneumonectomy (EPP), we
      retrospectively evaluated the usefulness of metabolic response by
      fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT)
      after neoadjuvant chemotherapy to predict prognosis for patients with resectable
      malignant pleural mesothelioma (MPM) who underwent EPP in a multicenter study.
      PATIENTS AND METHODS: We carried out high-resolution CT (HRCT) and FDG-PET/CT
      before and after neoadjuvant platinum-based chemotherapy on 50 patients with
      clinical T1-3 N0-2 M0 MPM who underwent EPP +/- postoperative hemithoracic
      radiotherapy. A decrease of >=30% in the tumor maximum standardized uptake value
      (SUVmax) was defined as a metabolic responder. The radiologic response using the
      modified RECIST or metabolic response and surgical results were analyzed.
      RESULTS: The median overall survival (OS) from diagnosis was 20.5 months.
      Metabolic responders significantly correlated to OS with median OS for metabolic
      responders not reached versus 18.7 months for non-responders. No correlation was
      observed between OS and radiologic response with median OS for radiologic
      responders and non-responders. Based on the multivariate Cox analyses, decreased
      SUVmax and epithelioid subtype were significantly independent factors for OS.
      CONCLUSIONS: The metabolic response after neoadjuvant chemotherapy is an
      independent prognostic factor for patients with resectable MPM. Patients with
      metabolic responder or epithelioid subtype may be good candidates for EPP.

PMID- 23136226
TI  - Intravenous injection of bortezomib, melphalan and dexamethasone in refractory
      and relapsed multiple myeloma.
AB  - BACKGROUND: A combination of bortezomib (1.3 mg/m(2)), melphalan (5 mg/m(2)), and
      dexamethasone (40 mg) (BMD), with all three drugs given as a contemporary
      intravenous administration, was retrospectively evaluated. PATIENTS AND METHODS:
      Fifty previously treated (median 2 previous lines) patients with myeloma (33
      relapsed and 17 refractory) were assessed. The first 19 patients were treated
      with a twice-a-week (days 1, 4, 8, 11, 'base' schedule) administration while, in
      the remaining 31 patients, the three drugs were administered once a week (days 1,
      8, 15, 22, 'weekly' schedule). RESULTS: Side-effects were predictable and
      manageable, with prominent haematological toxicity, and a better toxic profile in
      'weekly' schedule (36% versus 66% in 'base' schedule). The overall response rate
      was 62%. After median follow-up of 24.5 months (range 2.7-50 months), the median
      progression-free survival (PFS) was 21.6 with no difference between the two
      schedules and the median overall survival (OS) was 33.8 months. Independently
      from the adopted schedule, we found that also in a cohort of relapsed/refractory
      patients achieving at least partial remission improved PFS (35.2 versus 9 months)
      and OS (unreached median versus 18 months). CONCLUSION: Taken together, our
      observations suggest that BMD is an effective regimen in advanced myeloma
      patients with acceptable toxicity.

PMID- 23136225
TI  - Efficacy of abbreviated Stanford V chemotherapy and involved-field radiotherapy
      in early-stage Hodgkin lymphoma: mature results of the G4 trial.
AB  - INTRODUCTION: To assess the efficacy of an abbreviated Stanford V regimen in
      patients with early-stage Hodgkin lymphoma (HL). PATIENTS AND METHODS PATIENTS:
      with untreated nonbulky stage I-IIA supradiaphragmatic HL were eligible for the
      G4 study. Stanford V chemotherapy was administered for 8 weeks followed by
      radiation therapy (RT) 30 Gy to involved fields (IF). Freedom from progression
      (FFP), disease-specific survival (DSS) and overall survival (OS) were estimated.
      RESULTS: All 87 enrolled patients completed the abbreviated regimen. At a median
      follow-up of 10 years, FFP, DSS and OS are 94%, 99% and 94%, respectively.
      Therapy was well tolerated with no treatment-related deaths. CONCLUSIONS: Mature
      results of the abbreviated Stanford V regimen in nonbulky early-stage HL are
      excellent and comparable to the results from other contemporary therapies.

PMID- 23136227
TI  - Treatment and complications in elderly stage III colon cancer patients in the
      Netherlands.
AB  - BACKGROUND: We evaluated which patient factors were associated with treatment
      tolerance and outcome in elderly colon cancer patients. DESIGN: Population-based
      data from five regions included in the Netherlands Cancer Registry were used.
      Patients with resected stage III colon cancer aged >=75 years diagnosed in 1997
      2004 who received adjuvant chemotherapy (N = 216) were included as well as a
      random sample (N = 341) of patients who only underwent surgery. RESULTS: The most
      common motives for withholding adjuvant chemotherapy were a combination of high
      age, co-morbidity and poor performance status (PS, 43%) or refusal by the patient
      or family (17%). In 57% of patients receiving chemotherapy, adaptations were made
      in treatment regimens. Patients who received adjuvant chemotherapy developed more
      complications (52%) than those with surgery alone (41%). For the selection of
      patients who had survived the first year after surgery, receiving adjuvant
      chemotherapy resulted in better 5-year overall survival (52% versus 34%), even
      after adjustment for differences in age, co-morbidity and PS. CONCLUSION: Despite
      high toxicity rates and adjustments in treatment regimens, elderly patients who
      received chemotherapy seemed to have a better survival. Prospective studies are
      needed for evaluating which patient characteristics predict the risks and
      benefits of adjuvant chemotherapy in elderly colon cancer patients.

PMID- 23136228
TI  - Prospective analysis of vitamin D and endometrial cancer risk.
AB  - BACKGROUND: This is the first prospective cohort analysis on the association
      between vitamin D and endometrial cancer incorporating time-varying predicted
      plasma 25-hydroxyvitamin D [25(OH)D]. METHODS: The prospective cohort analysis of
      predicted 25(OH)D and total dietary vitamin D intake used the Cox proportional
      hazards model, and involved 644 incident endometrial cancer events from 1986 to
      2006 in the Nurses' Health Study. Genotyping and unconditional logistic
      regression were carried out on 572 endometrial cancer cases and their matched
      controls on 12 single nucleotide polymorphisms (SNPs) in vitamin D-related genes.
      RESULTS: There was no significant association between predicted 25(OH)D and
      endometrial cancer incidence, with the hazard ratio for the highest (versus the
      lowest) quintile of predicted 25(OH)D as 1.00 (95% CI 0.73-1.36) (p-trend =
      0.33). There was also no significant association involving total dietary vitamin
      D. No significant associations between any of the vitamin D-related SNPs and
      endometrial cancer were observed. CONCLUSION: Both predicted 25(OH)D and total
      dietary vitamin D intake were not associated with endometrial cancer incidence.
      These results suggest that vitamin D may not protect against the development of
      endometrial cancer. However, the low and narrow vitamin D exposure range in the
      cohort may limit generalizability of the results.

PMID- 23136229
TI  - From randomized trials to the clinic: is it time to implement individual lung
      cancer screening in clinical practice? A multidisciplinary statement from French
      experts on behalf of the French intergroup (IFCT) and the groupe d'Oncologie de
      langue francaise (GOLF).
AB  - BACKGROUND: Despite advances in cancer therapy, mortality is still high except in
      early-stage tumors, and screening remains a challenge. The randomized National
      Lung Screening Trial (NLST), comparing annual low-dose computed tomography (LDCT)
      and chest X-rays, revealed a 20% decrease in lung-cancer-specific mortality.
      These results raised numerous questions. The French intergroup for thoracic
      oncology and the French-speaking oncology group convened an expert group to
      provide a coherent outlook on screening modalities in France. METHODS: A
      literature review was carried out and transmitted to the expert group, which was
      divided into three workshops to tackle specific questions, with responses
      presented in a plenary session. A writing committee drafted this article.
      RESULTS: The multidisciplinary group favored individual screening in France, when
      carried out as outlined in this article and after informing subjects of the
      benefits and risks. The target population involves subjects aged 55-74 years, who
      are smokers or have a 30 pack-year smoking history. Subjects should be informed
      about the benefits of quitting. Screening should involve LDCT scanning with
      specific modalities. Criteria for CT positivity and management algorithms for
      positive examinations are given. CONCLUSIONS: Individual screening requires
      rigorous assessment and precise research in order to potentially develop a lung
      cancer screening policy.

PMID- 23136230
TI  - Prognostic factors for survival after complete resections of synchronous lung
      cancers in multiple lobes: pooled analysis based on individual patient data.
AB  - BACKGROUND: Some reports suggest that patients with synchronous multiple foci of
      nonsmall-cell lung cancers (NSCLC) distributed in multiple lobes have a poor
      prognosis, even when there is no extrathoracic metastasis. The vast majority of
      such patients do not receive surgical treatment. For those who undergo surgery,
      prognostic factors are unclear. PATIENTS AND METHODS: We systematically reviewed
      the literature on surgery for synchronous NSCLC in multiple lobes published
      between 1990 and 2011. Individual patient data were used to obtain adjusted
      hazard ratios (HRs) in each dataset and pooled analyses were carried out.
      RESULTS: Six studies contributed 467 eligible patients for analysis. The median
      overall survival was 52.0 months [95% confidence interval 45.6-63.7]. Male gender
      and advanced age were associated with a decreased survival: HRs 1.64 (1.22, 2.22)
      and 1.40 (1.20, 1.80) per 20-year increment, respectively. Patients with cancers
      distributed in one lung had a higher mortality risk than those with bilateral
      disease: HRs 1.45 (1.06, 2.00). N1 or N2 had a decreased survival compared with
      N0: HRs 1.68 (1.12, 2.51) and 1.94 (1.33, 2.82), respectively. There was a trend
      toward increased mortality among patients with different histology: HRs 1.29
      (0.96, 1.75). CONCLUSION: Advanced age, male gender, nodal involvement, and
      unilateral tumor location were poor prognostic factors.

PMID- 23136231
TI  - Prospective, open-label, randomized, phase III study of two dose-dense regimens
      MVAC versus gemcitabine/cisplatin in patients with inoperable, metastatic or
      relapsed urothelial cancer: a Hellenic Cooperative Oncology Group study (HE
      16/03).
AB  - BACKGROUND: The combinations of methotrexate, vinblastine, Adriamycin, cisplatin
      (Pharmanell, Athens, Greece) (MVAC) or gemcitabine, cisplatin (GC) represent the
      standard treatment of advanced urothelial cancer (UC). Dose-dense (DD)-MVAC has
      achieved longer progression-free survival (PFS) than the conventional MVAC.
      However, the role of GC intensification has not been studied. We conducted a
      randomized, phase III study comparing a DD-GC regimen with DD-MVAC in advanced
      UC. PATIENTS AND METHODS: One hundred and thirty patients were randomly assigned
      between DD-MVAC: 66 (M 30 mg/m(2), V 3 mg/m(2), A 30 mg/m(2), C 70 mg/m(2) q 2
      weeks) and DD-GC 64 (G 2500 mg/m(2), C 70 mg/m(2) q 2 weeks). The median follow
      up was 52.1 months (89 events). RESULTS: The median overall survival (OS) and PFS
      were 19 and 8.5 months for DD-MVAC and 18 and 7.8 months for DD-GC (P = 0.98 and
      0.36, respectively). Neutropenic infections were less frequent for DD-GC than for
      DD-MVAC (0% versus 8%). More patients on DD-GC received at least six cycles of
      treatment (85% versus 63%, P = 0.011) and the discontinuation rate was lower for
      DD-GC (3% versus 13%). CONCLUSIONS: Although DD-GC was not superior to DD-MVAC,
      it was better tolerated. DD-GC could be considered as a reasonable therapeutic
      option for further study in this patient population. Clinical Trial Number
      ACTRN12610000845033, www.anzctr.org.au.

PMID- 23136232
TI  - Dose escalation study of carboplatin-pemetrexed followed by maintenance
      pemetrexed for elderly patients with advanced nonsquamous nonsmall-cell lung
      cancer.
AB  - BACKGROUND: This study was designed to determine the recommended dose of
      carboplatin-pemetrexed in elderly (>=75 years old), chemotherapy-naive patients
      with advanced nonsquamous nonsmall-cell lung cancer (NSCLC). PATIENTS AND
      METHODS: Patients received escalated doses of carboplatin and pemetrexed every 3
      weeks for four cycles. Patients with an objective response and stable disease
      continued pemetrexed therapy until disease progression or unacceptable toxicity
      was observed. RESULTS: The combination of carboplatin at an area under the
      concentration-time curve (AUC) of 5, and 500 mg/m(2) pemetrexed, was determined
      to be the recommended dose for elderly patients with advanced nonsquamous NSCLC.
      Of 17 patients, 10 received a median of five cycles of pemetrexed maintenance
      therapy without unexpected or cumulative toxic effects. The study had an overall
      response rate of 47.1%. The median progression-free survival time was 142 days
      (95% confidence interval [CI] 68-216 days) and the median overall survival time
      was 461 days (95% CI 168-754 days). CONCLUSIONS: This combination was a tolerable
      and effective regimen, and recommended dose (RD) was carboplatin [area under the
      curve (AUC) of 5]/pemetrexed (500 mg/m(2)) every 3 weeks, in chemotherapy-naive,
      elderly (>=75 years old) patients with advanced nonsquamous NSCLC.

PMID- 23136233
TI  - The 21-gene recurrence score assay impacts adjuvant therapy recommendations for
      ER-positive, node-negative and node-positive early breast cancer resulting in a
      risk-adapted change in chemotherapy use.
AB  - BACKGROUND: We carried out a prospective clinical study to evaluate the impact of
      the Recurrence Score (RS) on treatment decisions in early breast cancer (EBC).
      PATIENTS AND METHODS: A total of 379 eligible women with estrogen receptor
      positive (ER+), HER2-negative EBC and 0-3 positive lymph nodes were enrolled.
      Treatment recommendations, patients' decisional conflict, physicians' confidence
      before and after knowledge of the RS and actual treatment data were recorded.
      RESULTS: Of the 366 assessable patients 244 were node negative (N0) and 122 node
      positive (N+). Treatment recommendations changed in 33% of all patients (N0 30%,
      N+ 39%). In 38% of all patients (N0 39%, N+ 37%) with an initial recommendation
      for chemoendocrine therapy, the post-RS recommendation changed to endocrine
      therapy, in 25% (N0 22%, N+ 39%) with an initial recommendation for endocrine
      therapy only to combined chemoendocrine therapy, respectively. A patients'
      decisional conflict score improved by 6% (P = 0.028) and physicians' confidence
      increased in 45% (P < 0.001) of all cases. Overall, 33% (N0 29%, N+ 38%) of fewer
      patients actually received chemotherapy as compared with patients recommended
      chemotherapy pre-test. Using the test was cost-saving versus current clinical
      practice. CONCLUSION: RS-guided chemotherapy decision-making resulted in a
      substantial modification of adjuvant chemotherapy usage in node-negative and node
      positive ER+ EBC.

PMID- 23136234
TI  - The contribution of molecular epidemiology to the identification of human
      carcinogens: current status and future perspectives.
AB  - BACKGROUND: The use of biological-based markers of exposure, intermediate effect,
      outcome, and susceptibility has become standard practice in cancer epidemiology,
      which has contributed to identification of several carcinogenic agents.
      Nevertheless, with the exception of biological agents, this contribution, in
      terms of providing sufficiently strong evidence as required by the International
      Agency for Research on Cancer (IARC) monographs, has been modest. MATERIALS AND
      METHODS: We discuss the overall contribution of molecular epidemiology to
      identification of carcinogens, with focus on IARC monographs. RESULTS: For many
      carcinogens, valid biological markers of exposure and mechanisms of actions are
      not available. Molecular markers are usually assessed in single biological
      samples, which may not represent the actual exposure or biological events related
      to carcinogens. The contribution of molecular epidemiology to identification of
      carcinogens has mainly been limited to the carcinogens acting through a genotoxic
      mechanism, i.e. when carcinogens induce DNA damage. A number of factors,
      including certain hormones and overweight/obesity, may show carcinogenic effects
      through nongenotoxic pathways, for which mechanisms of carcinogenicity are not
      well identified and their biomarkers are sparse. CONCLUSION: Longitudinal
      assessment of biomarkers may provide more informative data in molecular
      epidemiology studies. For many carcinogens and mechanistic pathways, in
      particular nongenotoxic carcinogenicity, valid biological markers still need to
      be identified.

PMID- 23136235
TI  - The FACT-G7: a rapid version of the functional assessment of cancer therapy
      general (FACT-G) for monitoring symptoms and concerns in oncology practice and
      research.
AB  - BACKGROUND: Health-related quality-of-life (HRQOL) assessments in research and
      clinical oncology settings are increasingly important. HRQOL instruments need to
      be rapid and still maintain the ability to capture the most relevant patient
      issues in a valid and reliable manner. The current study develops and validates
      the FACT-G7, a rapid version of the Functional Assessment of Cancer Therapy
      General (FACT-G). PATIENTS AND METHODS: Oncology patients with advanced cancer (N
      = 533) from 11 diseases sites ranked the symptoms and concerns they viewed as
      'the very most important' when undergoing cancer treatment, completed the FACT-G,
      and additional HRQOL measures. Oncology patients' scores were referenced across a
      general US population sample (N = 2000). RESULTS: We selected the highest
      priority cancer-related symptoms and concerns endorsed by patients for inclusion
      in the FACT-G7. Fatigue and ability to enjoy life were ranked the most highly.
      The results provide preliminary support for the FACT-G7's internal consistency
      reliability (alpha = 0.74) and validity as evidenced by moderate-to-strong
      relationships with expected criteria. The references for the general population
      are summarized. CONCLUSIONS: The FACT-G7 can be used to assess top-rated symptoms
      and concerns for a broad spectrum of advanced cancers in clinical practice and
      research.

PMID- 23136236
TI  - Successful treatment of cerebral venous sinus thrombosis with the Solitaire FR
      thrombectomy device.
AB  - A young woman with factor V Leiden thrombophilia presented with headache due to
      thrombosis of the right transverse sinus (TS) and superior sagittal sinus.
      Despite appropriate anticoagulation, she experienced worsening headache,
      progressive neurologic deficits and spontaneous subarachnoid hemorrhage.
      Endovascular therapy was therefore undertaken. A 6 mm Solitaire FR device was
      deployed in the TS and withdrawn in a stepwise fashion, resulting in complete
      recanalization of the sinus. Her headache improved and her neurologic deficits
      resolved. Endovascular therapy for cerebral venous sinus thrombosis is currently
      recommended only for those patients with deterioration despite appropriate
      anticoagulation. The thrombus burden is usually high in this subset of patients,
      and recanalization can be challenging with currently available endovascular
      techniques. This is the first report of cerebral venous sinus thrombectomy with
      the Solitaire FR device, which may offer another option for those patients
      requiring endovascular treatment. 

PMID- 23136237
TI  - Balloon remodeling for aneurysm coil embolization with the coaxial lumen Scepter
      C balloon catheter: initial experience at a high volume center.
AB  - INTRODUCTION: The use of balloon remodeling allows for the treatment of aneurysms
      that were previously considered to be poor candidates for coil embolization. The
      Scepter C (Microvention, Tustin, California, USA) is a novel temporary occlusion
      balloon system with a dual coaxial lumen catheter. The design accommodates a more
      steerable 0.014 inch guidewire with improved control for delivery to the target
      lesion. We describe our initial experience with the use of this device for
      balloon remodeling to assist during aneurysm coil embolization. METHODS: All
      aneurysms that were treated with balloon remodeling employing the Scepter C
      balloon at a single institution (Medical University of South Carolina) from the
      time it was available in October 2011 to July 2012 were evaluated. Patient
      demographics, aneurysm characteristics, procedural success, and adverse events
      were assessed. RESULTS: 52 aneurysms were treated in 48 patients (45 women, three
      men) with a mean age of 59.3 +/- 11 years (mean +/- SD). Mean aneurysm height was
      5.9 +/- 3 mm, width 4.4 +/- 2 mm with a 3.1 +/- 2 mm broad neck. A variety of
      aneurysms were treated. The most commonly utilized size was the 4 mm * 10 mm
      (n=33) balloon. A Raymond 1 (complete occlusion) was achieved in the majority
      (n=44; 84.6%) of aneurysms, Raymond 2 (residual neck) in five, and Raymond 3
      (residual aneurysm) in five. There was one complication (1.9%) attributed
      directly to balloon use. CONCLUSIONS: Our initial experience with the dual
      coaxial lumen Scepter C occlusion balloon catheter demonstrates its feasibility
      for use in balloon remodeling for aneurysm coil embolization. A variety of
      aneurysms at different locations were treated with satisfactory initial
      angiographic results and adverse event rates.

PMID- 23136238
TI  - A double-blind, placebo-controlled study of the safety and efficacy of vitamin K1
      ointment for the treatment of patients with cetuximab-induced acneiform eruption.
AB  - A double-blind, placebo-controlled study evaluating the efficacy and safety of
      vitamin K1 ointment for the treatment of patients with cetuximab-induced
      acneiform eruption has started. Vitamin K1 ointment and placebo are applied twice
      daily for 8 consecutive weeks after the development of acneiform eruptions.
      Vitamin K1 ointment is applied in the middle of one side (face, neck or chest)
      and placebo is applied to the other side. The primary endpoint is the regression
      rate of acneiform eruptions on right- and left-side lesions in the same patient,
      compared with baseline at the final evaluation in the 10-week trial. The
      secondary endpoints include adverse events of acneiform eruption and other
      adverse events.

PMID- 23136239
TI  - Intratubular trophoblasts in the contralateral testis caused elevation of serum
      human chorionic gonadotropin following complete remission of stage II testicular
      tumor: a case report.
AB  - We report the case of a 22-year-old male who had a history of metastatic right
      testicular tumor successfully treated with chemotherapy and surgery. Twenty-one
      months after the initial treatment, the serum human chorionic gonadotropin
      started to increase gradually, but whole body imaging including the left testis
      revealed no abnormal finding except testicular microlithiasis. A biopsy of the
      left testis revealed intratubular germ cell neoplasia, unclassified type. After
      the human chorionic gonadotropin level reached 6.6 mIU/ml, he underwent left high
      orchiectomy. Histology demonstrated a small malignant germ cell tumor as well as
      intratubular germ cell neoplasia, unclassified type, both of which were negative
      for human chorionic gonadotropin staining. Besides these lesions, there were tiny
      foci of human chorionic gonadotropin-immunoreactive intratubular trophoblasts.
      Serum human chorionic gonadotropin normalized immediately after the orchiectomy,
      and he had no sign of recurrence at 6 months. The present case will provide new
      insight into the diagnosis of testicular tumor recurrence with isolated elevation
      of a serum tumor marker.

PMID- 23136240
TI  - A 12-mm carcinoid tumor of the minor duodenal papilla with lymph node metastases.
AB  - Carcinoid tumors located in the minor duodenal papilla are extremely rare, with
      only a few cases reported in the literature. Herein, we report the case of a 71
      year-old man with a 12-mm carcinoid tumor at the minor duodenal papilla with
      lymph node metastases. Multidetector-row computed tomography with contrast
      enhancement revealed a 12-mm well-enhanced tumor in the duodenum. Upper
      gastrointestinal endoscopy showed a 12-mm submucosal tumor at the minor papilla
      of the duodenum. Biopsy specimens revealed a carcinoid tumor, and a subtotal
      stomach-preserving pancreatoduodenectomy was performed. Carcinoid tumors at the
      minor duodenal papilla have a high prevalence of nodal disease, even for tumors
      <2 cm in diameter. Therefore, we believe that radical resection with tumor-free
      margins (i.e. pancreatoduodenectomy) is the treatment of choice.

PMID- 23136241
TI  - Forget personalised medicine and focus on abating disease activity.
AB  - In this viewpoint, we summarise three different lines of evidence suggesting that
      current biological therapies directed at different molecules or cells have
      similar efficacy in rheumatoid arthritis and target similar populations of
      patients; therefore, distinct biological effects of targeted therapies may not
      account for differences in response. Moreover, currently available individual
      biomarkers or multiple biomarker sets do not provide information beyond that
      conveyed by clinical disease activity. Smart and novel research designs will have
      to be developed to find pertinent biomarkers. Until then, the focus of clinicians
      may have to solely rest on clinical disease activity assessment and targeting
      remission or low disease activity rapidly.

PMID- 23136242
TI  - Long-term safety of rituximab in rheumatoid arthritis: 9.5-year follow-up of the
      global clinical trial programme with a focus on adverse events of interest in RA
      patients.
AB  - OBJECTIVES: Evaluation of long-term safety of rituximab in rheumatoid arthritis
      (RA). METHODS: Pooled observed case analysis of data from patients with moderate
      to-severe, active RA treated with rituximab in a global clinical trial programme.
      RESULTS: As of September 2010, 3194 patients had received up to 17 rituximab
      courses over 9.5 years (11 962 patient-years). Of these, 627 had >5 years' follow
      up (4418 patient-years). A pooled placebo population (n=818)
      (placebo+methotrexate (MTX)) was also analysed. Serious adverse event and
      infection rates generally remained stable over time and multiple courses. The
      overall serious infection event (SIE) rate was 3.94/100 patient-years (3.26/100
      patient-years in patients observed for >5 years) and was comparable with
      placebo+MTX (3.79/100 patient-years). Serious opportunistic infections were rare.
      Overall, 22.4% (n=717) of rituximab-treated patients developed low immunoglobulin
      (Ig)M and 3.5% (n=112) low IgG levels for >=4 months after >=1 course. SIE rates
      were similar before and during/after development of low Ig levels; however, in
      patients with low IgG, rates were higher than in patients who never developed low
      IgG. Rates of myocardial infarction and stroke were consistent with rates in the
      general RA population. No increased risk of malignancy over time was observed.
      CONCLUSIONS: This analysis demonstrates that rituximab remains generally well
      tolerated over time and multiple courses, with a safety profile consistent with
      published data and clinical trial experience. Overall, the findings indicate that
      there was no evidence of an increased safety risk or increased reporting rates of
      any types of adverse events with prolonged exposure to rituximab during the 9.5
      years of observation.

PMID- 23136243
TI  - Counterpoint: cancer stem cells: nonbelievers' viewpoint.

PMID- 23136244
TI  - Oral cancer diagnosis via a ferrocenylnaphthalene diimide-based electrochemical
      telomerase assay.
AB  - BACKGROUND: Telomerase is regarded as a good marker for cancer because it is
      unregulated in most tumor cells compared with normal cells. We evaluated
      telomerase activity in the lysate of tumor tissue and surrounding cells of oral
      cancer patients by an electrochemical technique, dubbed the electrochemical
      telomerase assay (ECTA). METHODS: The assay used ferrocenylnaphthalene diimide
      (FND) as the probe. Electrochemical telomerase substrate (ETS) primer immobilized
      on the electrode was elongated by telomerase and FND bound to the product to give
      rise to a current. The data were standardized with the change in current before
      and after the elongation, respectively. RESULTS: The change in current increased
      more than 30% in biopsy samples from most cancer patients, whereas the increase
      was 20% or lower in most healthy individuals. On the basis of this difference
      individual clinical samples were judged telomerase positive, ambiguous, or
      negative. The positive rates in the cancerous tissues and exfoliated cells (EOCs)
      of the patients were 85% and 90%, respectively, whereas the corresponding values
      were 50% and 10% by the telomerase repeat amplification protocol. Furthermore,
      the positive rate for the ECTA was 100% in early tumors smaller than 2 cm, and
      95% and 82% of biopsy and exfoliated cells of healthy individuals were correctly
      judged as negative. Fifty-six unknown samples with EOCs tested were correctly
      judged to be cancerous or normal in 84% of cases. CONCLUSIONS: The ECTA yielded
      high hit rates for cancerous and normal cells, especially in EOCs, results
      indicating that this minimally invasive test is suitable for oral cancer
      diagnosis.

PMID- 23136245
TI  - GALNT9 gene expression is a prognostic marker in neuroblastoma patients.
AB  - BACKGROUND: The enzymes encoded by the GALNT [UDP-N-acetyl-alpha-d
      galactosamine:polypeptide N-acetylgalactosaminyltransferase (GALNAC-T)] gene
      family catalyze the first step of O-glycosylation. Little is known about the link
      between expression of the genes encoding GALNAC-T enzymes and tumor progression
      in neuroblastoma, a pediatric cancer that can be classified as either low or high
      risk. We assessed the expression of genes in the GALNT family in a large cohort
      of neuroblastoma patients and characterized members of this family that might be
      used as new prognostic markers. METHODS: Reverse-transcription PCR analysis of 14
      GALNT genes with a panel of neuroblastoma cell lines identified the GALNT9 gene
      as playing a potential role in disease progression. We used the log-rank test and
      the multivariable Cox proportional hazards model with a cohort of 122
      neuroblastoma patients to analyze the relationship between GALNT9 expression and
      overall survival or disease-free survival. RESULTS: In the high-risk
      neuroblastoma experimental model IGR-N-91, GALNT9 expression was present in
      neuroblasts derived from primary tumors but not in neuroblasts from metastatic
      bone marrow. Moreover, GALNT9 in neuroblastoma cell lines was expressed in
      substrate adherent (S)-type cell lines but not in neuronal (N)-type lines. In the
      tumor cohort, GALNT9 expression was associated with high overall survival,
      independent of the standard risk-stratification covariates. GALNT9 expression was
      significantly associated with disease-free survival for patients currently
      classified as at low risk (P < 0.0007). CONCLUSIONS: GALNT9 expression correlates
      with both improved overall survival in low- and high-risk groups and an improved
      clinical outcome (overall and disease-free survival) in low-risk patients. Thus,
      the GALNT9 expression may be a prognostic marker for personalized therapy.

PMID- 23136246
TI  - Downregulation and prognostic performance of microRNA 224 expression in prostate
      cancer.
AB  - INTRODUCTION: The extensive use of prostate-specific antigen as a general
      prostate cancer biomarker has introduced the hazards of overdiagnosis and
      overtreatment. Recent studies have revealed the immense biomarker capacity of
      microRNAs (miRNAs) in prostate cancer. The aim of this study was to analyze the
      expression pattern of miR-224, a cancer-related miRNA, in prostate tumors and
      investigate its clinical utility. METHODS: Total RNA was isolated from 139
      prostate tissue samples. After the polyadenylation of total RNA by poly(A)
      polymerase, cDNA was synthesized with a suitable poly(T) adapter. miR-224
      expression was assessed by quantitative real-time PCR and analyzed with the
      comparative quantification cycle method, C(q)(2(-DeltaDeltaCq)). We performed
      comprehensive biostatistical analyses to explore the clinical value of miR-224 in
      prostate cancer. RESULTS: miR-224 expression was significantly downregulated in
      malignant samples compared with benign samples (P < 0.001). Higher miR-224
      expression levels were found in prostate tumors that were less aggressive (P =
      0.017) and in an earlier disease stage (P = 0.018). Patients with prostate cancer
      who were positive for miR-224 had significantly enhanced progression-free
      survival intervals compared with miR-224-negative patients (P = 0.021).
      Univariate bootstrap Cox regression confirmed that miR-224 was associated with
      favorable prognosis (hazard ratio 0.314, P = 0.013); nonetheless, multivariate
      analysis, adjusted for conventional markers, did not identify miR-224 as an
      independent prognostic indicator. CONCLUSIONS: miR-224 is aberrantly expressed in
      prostate cancer. Its assessment by cost-effective quantitative molecular
      methodologies could provide a useful biomarker for prostate cancer.

PMID- 23136247
TI  - Heterogeneity of epidermal growth factor receptor status and mutations of
      KRAS/PIK3CA in circulating tumor cells of patients with colorectal cancer.
AB  - BACKGROUND: Molecular characterization of circulating tumor cells (CTCs) is
      pivotal to increasing the diagnostic specificity of CTC assays and investigating
      therapeutic targets and their downstream pathways on CTCs. We focused on
      epidermal growth factor receptor (EGFR) and genes relevant for its inhibition in
      patients with colorectal cancer (CRC). METHODS: We used the CellSearch(r) system
      for CTC detection in peripheral blood samples from 49 patients with metastatic
      CRC (mCRC) and 32 patients with nonmetastatic CRC (nmCRC). We assessed EGFR
      expression in 741 CTCs from 27 patients with mCRC and 6 patients with nmCRC using
      a fluorescein-conjugated antibody with the CellSearch Epithelial Cell Kit. DNA of
      a single CTC isolated by micromanipulation was propagated by whole-genome
      amplification and analyzed by quantitative PCR for EGFR gene amplification and
      sequencing for KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog), BRAF
      (v-raf murine sarcoma viral oncogene homolog B1), and PIK3CA
      (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha)
      mutations. RESULTS: At least 2 CTCs were detected in 24 of 49 patients with mCRC
      and 7 of 32 patients with nmCRC. In 7 of 33 patients, CTCs with increased EGFR
      expression were identified. Heterogeneity in EGFR expression was observed between
      CTCs from the same patient. EGFR gene amplification was found in 7 of 26 CTCs
      from 3 patients. The investigated BRAF gene locus was not mutated in 44 analyzed
      CTCs, whereas KRAS mutations were detected in 5 of 15 CTCs from 1 patient and
      PIK3CA mutations in 14 of 36 CTCs from 4 patients. CONCLUSIONS: Molecular
      characterization of single CTCs demonstrated considerable intra- and interpatient
      heterogeneity of EGFR expression and genetic alterations in EGFR, KRAS, and
      PIK3CA, possibly explaining the variable response rates to EGFR inhibition in
      patients with CRC.

PMID- 23136248
TI  - Reflections on the founding of the International Cancer Genome Consortium.

PMID- 23136249
TI  - TMPRSS2-ERG fusion transcripts in matched urine and needle rinse material after
      biopsy for the detection of prostate cancer: really a step forward?

PMID- 23136250
TI  - Copy number and expression alterations of miRNAs in the ovarian cancer cell line
      OVCAR-3: impact on kallikrein 6 protein expression.
AB  - BACKGROUND: Kallikrein-related peptidase 6 (KLK6), a member of the serine
      protease family of kallikrein (KLK) genes, is dysregulated in ovarian carcinomas
      (OCa) and its overexpression is associated with poor prognosis. Regulation of its
      expression is poorly understood and is likely to be influenced by multiple
      mechanisms. The KLK locus is subject to copy number changes and heterogeneity in
      serous OCas. These copy number imbalances generally correlate with KLK6 protein
      expression; however, this is not always the case. In this study we explored the
      role of miRNAs in the posttranscriptional control of KLK6 expression and the
      contributions of copy numbers, not only of the KLK locus, but also of the miRNAs
      predicted to regulate it. METHODS AND RESULTS: By miRNA profiling of the KLK6
      overexpressing OCa cell line, OVCAR-3, we identified overexpressed and
      underexpressed miRNAs. Publically available miRNA databases identified the human
      miRNA lethal 7 (hsa-let-7) family members as putative regulating miRNAs, from
      which hsa-let-7a was chosen for functional analysis. The transient transfection
      of hsa-let-7a to OVCAR-3 resulted in a decrease of KLK6 secreted protein.
      Moreover, such transfection was also able to weakly affect the expression of
      another member of the KLK gene family, KLK10 (kallikrein-related peptidase 10).
      Cytogenomic analysis, including array comparative genomic hybridization,
      fluorescence in situ hybridization, and spectral karyotyping revealed the overall
      net copy number losses of hsa-let-7a and other miRNAs predicted to target KLK6.
      CONCLUSIONS: The hsa-let-7 family member hsa-let-7a is a modulator of KLK6
      protein expression that is independent of the KLK6 copy number status.

PMID- 23136251
TI  - SOX17 promoter methylation in circulating tumor cells and matched cell-free DNA
      isolated from plasma of patients with breast cancer.
AB  - INTRODUCTION: Detection of circulating tumor cells (CTCs) and cell-free DNA
      (cfDNA) in the peripheral blood of patients with solid tumors has been widely
      studied for the early detection of metastatic spread. We evaluated whether there
      was an association between the origin of cfDNA and CTCs. We investigated whether
      SRY (sex determining region Y)-box 17 (SOX17) promoter methylation in CTCs was
      associated with the methylation pattern of this gene in matched cfDNA isolated
      from plasma of patients with breast cancer. METHODS: We examined SOX17
      methylation in 79 primary breast tumors, in 114 paired samples of DNA isolated
      from CTCs and cfDNA, and in 60 healthy individuals. Isolated DNA was modified by
      sodium bisulfite and subjected to methylation specific PCR. RESULTS: The SOX17
      promoter was methylated in 68 (86.0%) of 79 of primary breast tumors. In CTCs,
      SOX17 was methylated in 19 (34.5%) of 55 patients with early breast cancer, 27
      (45.8%) of 59 patients with metastatic cancer, and 1 (4.3%) of 23 healthy
      individuals, whereas in matched cfDNA SOX17 was methylated in 19 (34.5%) of 55,
      24 (40.7%) of 59, and 1 (2.0%) of 49 of these same groups, respectively. There
      was a significant correlation between SOX17 methylation in cfDNA and CTCs in
      patients with early breast cancer (P = 0.008), but not in patients with verified
      metastasis (P = 0.283). CONCLUSIONS: The SOX17 promoter is highly methylated in
      primary breast tumors, in CTCs isolated from patients with breast cancer, and in
      corresponding cfDNA samples. Our findings indicate a direct connection between
      the presence of CTCs and cfDNA in patients with operable breast cancer, after
      surgical removal of the primary tumor.

PMID- 23136252
TI  - External quality assessment of point-of-care methods: model for combined
      assessment of method bias and single-participant performance by the use of native
      patient samples and noncommutable control materials.
AB  - BACKGROUND: An important objective in external quality assessment (EQA) is to
      evaluate systematic deviations between methods. However, this is not possible
      when noncommutable control materials are used. The aim of this study was to
      develop an EQA model that incorporates a method bias evaluation using native
      patient samples into EQA schemes in which noncommutable materials are used.
      METHODS: The model was applied twice in a point-of-care (POC) international
      normalized ratio survey among 1341 and 1578 participants. To estimate bias, about
      100 native patient samples for each POC method were analyzed by a selected group
      of "expert" primary healthcare centers and on a designated comparison method. In
      addition, the expert centers as well as all the other EQA participants analyzed 2
      noncommutable control materials, and method-specific target values were
      established. Both method bias and the deviation of a single-participant result
      from the method target value were evaluated against analytical quality
      specifications, making combined assessment possible. The best-case scenario
      occurred when both results were within the quality specifications. RESULTS: Two
      POC methods fulfilled the quality specification for bias, whereas one did not.
      The best-case scenario was achieved by more than 90% of the participants using
      the methods with no bias, whereas none of the participants using the method with
      unacceptable bias achieved this result. CONCLUSIONS: We propose an EQA model for
      which the bias of POC methods can be evaluated in situations in which commutable
      control materials are not available.

PMID- 23136253
TI  - Pancreatic cancer.

PMID- 23136255
TI  - High-sensitivity C-reactive protein levels and cancer mortality.
AB  - BACKGROUND: High-sensitivity C-reactive protein (hs-CRP) is an important
      inflammatory marker, and inflammation is known to be involved in the initiation
      and progression of cancer. We investigated the association between serum hs-CRP
      levels and all-cause mortality, cancer mortality, and site-specific cancer
      mortality in apparently cancer-free Koreans. METHODS: A total of 33,567
      participants who underwent routine check-ups at a single tertiary hospital health
      screening center between May 1995 and December 2006, and whose serum hs-CRP level
      data were available, were included in the study. Baseline serum hs-CRP levels
      were obtained and subjects were followed up for mortality from baseline
      examination until December 31, 2008. RESULTS: During an average follow-up of 9.4
      years, 1,054 deaths, including 506 cancer deaths, were recorded. The adjusted HRs
      (aHR; 95% confidence interval [CI]) of subjects with hs-CRP >=3 mg/L for all
      cause and cancer-related mortality were 1.38 (1.15-1.66) and 1.61 (1.25-2.07) in
      men, and 1.29 (0.94-1.77) and 1.24 (0.75-2.06) in women, respectively, compared
      with subjects with hs-CRP <=1 mg/L. Elevated hs-CRP was also associated with an
      increased risk of site-specific mortality from lung cancer for sexes combined
      (2.53 [1.57-4.06]). CONCLUSIONS: This study suggests that elevated levels of hs
      CRP in apparently cancer-free individuals may be associated with increased
      mortality from all-causes and cancer, in particular, lung cancer in men, but not
      in women. IMPACT: As a marker for chronic inflammation, hs-CRP assists in the
      identification of subjects with an increased risk of cancer death.

PMID- 23136256
TI  - The granulocyte-colony stimulating factor receptor (G-CSFR) interacts with
      retinoic acid receptors (RARs) in the regulation of myeloid differentiation.
AB  - The key roles of RARs and G-CSFR in the regulation of granulopoiesis have been
      well-documented. In this study, we sought to investigate the interaction between
      G-CSFR and RARs in myeloid differentiation of adult mice through conditional
      deletion of RARalpha or RARgamma on a G-CSFR(-/-) background and by
      pharmacological intervention of WT and G-CSFR(-/-) mice with a pan-RAR inverse
      agonist, NRX194310. Our findings show that residual granulopoiesis still persists
      in mice doubly null for G-CSFR and RARalpha or RARgamma, confirming that RARs and
      G-CSFR are dispensable in maintaining residual granulopoiesis. Moreover, an
      increase in mature myeloid cells was seen in the conditional
      RARgamma(Delta/Delta) mice and WT mice treated with NRX194310, likely mediated
      through increased G-CSF production. However, with the loss of G-CSFR, this
      expansion in granulopoiesis was attenuated, supporting the hypothesis that G-CSFR
      signaling interacts with RARs in the regulation of myeloid differentiation.

PMID- 23136257
TI  - Aggressive disease defined by cytogenetics is associated with cytokine
      dysregulation in CLL/SLL patients.
AB  - Early treatment of CLL/SLL does not impact survival-reflecting limitations in
      detecting progression early and identifying asymptomatic patients likely to
      benefit from early treatment. Improved understanding of CLL/SLL biology would
      identify better prognostic/predictive markers. This study attempts to address
      these issues by determining the relationship between cytokine aberrations and
      poor clinical outcomes in CLL/SLL in the context of a genetic-based prognostic
      model. Fifty-nine serum cytokines/chemokines were measured in 28 untreated
      CLL/SLL patients. Patients were stratified as GR or int/PR using cytogenetics.
      Comparison of CLL/SLL with 28 HCs revealed increased expression of Th2 cytokines
      (IL-10, IL-5, sIL-2Ralpha; P<=0.01) and decreased levels of Th1 cytokines (IL-17,
      IL-23, IFN-gamma; P<=0.003). In a multivariate analysis of GR versus int/PR
      groups, differential expression of sIL-2Ralpha maintained significance with
      increased expression in int/PR CLL/SLL. With median follow-up of 54.3 months
      after diagnosis, four patients incurred disease progression, with an IL-17/sIL
      2Ralpha model predicting need for treatment in all cases. In summary, specific
      cytokine signatures are associated with genetically defined aggressive disease
      and predict need for therapy. This suggests utility in detecting disease
      progression early, identifying those likely to incur a survival advantage with
      early treatment, and directing future therapy.

PMID- 23136258
TI  - Tumor microenvironment converts plasmacytoid dendritic cells into
      immunosuppressive/tolerogenic cells: insight into the molecular mechanisms.
AB  - Human pDCs represent a rare population of circulating cells characterized by a
      rapid and massive TLR-dependent secretion of type I IFN in response to pathogenic
      agents or danger signals. Through their capacity to bring together innate and
      adaptive immunity and to secrete soluble factors controlling cancer development,
      these cells could represent important actors in antitumor immunity. However,
      accumulating evidence suggests that pDCs recruited to the tumor microenvironment
      often display a nonactivated state and are associated with the development and
      maintenance of immunosuppression. Here, we present an overview of neoplastic
      lesions associated with an infiltration of immunosuppressive/tolerogenic pDC.
      Moreover, as the proper response of pDC against cancer depends on a critical
      balance between immune-activating and immune-suppressing mechanisms, we summarize
      current knowledge about the molecular pathways developed by tumors to prevent
      antitumoral pDC immune responses. A better understanding of the mechanisms
      regulating pDC function in tumors could aid in the development of new therapies.
      Indeed, effective cancer vaccines or therapies could combine immunoactivating
      strategies (i.e., TLR agonists) with elimination of immune-suppressing
      mechanisms, leading to pDC reprogramming and thus, allowing tumor rejection in a
      clinical setting.

PMID- 23136260
TI  - Subdural empyema in bacterial meningitis.
AB  - OBJECTIVE: To evaluate the occurrence, treatment, and outcome of subdural empyema
      complicating community-acquired bacterial meningitis in adults. METHODS: Case
      series from a prospective nationwide cohort study from Dutch hospitals from 2006
      to 2011. RESULTS: Subdural empyema was diagnosed in 28 of 1,034 episodes (2.7%),
      and was present on admission in 10 episodes and diagnosed during admission in 18.
      Predisposing conditions were present in 26 patients (93%), and consisted of
      otitis or sinusitis in 21 patients (75%). In all these patients the otitis or
      sinusitis spread to the subdural space. Twenty-three patients (82%) presented
      with neurologic symptoms (paresis, focal seizures, dysesthesia contralateral to
      the empyema). Streptococcus pneumoniae was identified in 26 patients (93%) and
      Streptococcus pyogenes in 1 (3%); 1 patient had negative CSF cultures. Clinical
      course was frequently complicated with seizures (50%), focal neurologic
      abnormalities (54%), and hearing impairment (39%), causing an unfavorable outcome
      in 19 episodes (68%). Neurosurgical evacuation of the empyema was performed in 5
      patients, all with considerable midline shift. CONCLUSIONS: Although rare,
      subdural empyema must be considered in patients with community-acquired bacterial
      meningitis and otitis or sinusitis, focal neurologic deficits, or epileptic
      seizures. S pneumoniae is the predominant causative organism and neurosurgical
      intervention should be regarded as first-choice therapy in patients with empyema
      causing midline shift and focal neurologic abnormalities or a decreased level of
      consciousness.

PMID- 23136259
TI  - Current trends in inflammatory and immunomodulatory mediators in sepsis.
AB  - Sepsis refers to severe systemic inflammation in response to invading pathogens.
      An overwhelming immune response, as mediated by the release of various
      inflammatory mediators, can lead to shock, multiple organ damage, and even death.
      Cytokines, proteases, lipid mediators, gaseous substances, vasoactive peptides,
      and cell stress markers play key roles in sepsis pathophysiology. Various
      adhesion molecules and chemokines sequester and activate neutrophils into the
      target organs, further augmenting inflammation and tissue damage. Although the
      anti-inflammatory substances counterbalance proinflammatory mediators, prolonged
      immune modulation may cause host susceptibility to concurrent infections, thus
      reflecting enormous challenge toward developing effective clinical therapy
      against sepsis. To understand the complex interplay between pro- and anti
      inflammatory phenomenon in sepsis, there is still an unmet need to study newly
      characterized mediators. In addition, revealing the current trends of novel
      mediators will upgrade our understanding on their signal transduction, cross
      talk, and synergistic and immunomodulating roles during sepsis. This review
      highlights the latest discoveries of the mediators in sepsis linking to innate
      and adaptive immune systems, which may lead to resolution of many unexplored
      queries.

PMID- 23136261
TI  - Fat mass and obesity gene and cognitive decline: the Atherosclerosis Risk in
      Communities Study.
AB  - OBJECTIVE: To determine whether 4 genetic variants in the fat mass and obesity
      associated gene (FTO) identified in genome-wide association studies of diabetes
      and obesity are associated with cognitive change in midlife in the
      Atherosclerosis Risk in Communities (ARIC) Study. METHODS: ARIC is a prospective
      cohort study of the development of atherosclerosis in 15,792 individuals aged 45
      to 64 years at baseline from 1986 to 1989. FTO is highly expressed in human fetal
      and adult brain, and a single nucleotide polymorphism in FTO has previously been
      associated with reduced brain volume in cognitively normal subjects. Since a
      relationship between brain atrophy and diminished cognitive function has been
      demonstrated in ARIC participants, general linear models were used to evaluate
      the association between 6-year change in scores on 3 neuropsychological tests and
      FTO genotype. RESULTS: In a sample of 8,364 white and 2,083 African American men
      and women with no clinical history of stroke, significantly greater mean change
      in performance on the Delayed Word Recall Test was associated with 2 of 4 FTO
      single nucleotide polymorphisms examined (rs9939609, rs805136, rs17817449, and
      rs1421085) in whites but not in African Americans (p <= 0.002). The association
      of the FTO polymorphisms with cognitive change was independent of potential
      confounding clinical and demographic variables including age, gender, education,
      diabetes, hypertension, and body mass index. CONCLUSIONS: Further studies will be
      needed to clarify the biological mechanisms and genetic pathways through which
      variants in FTO can increase susceptibility to decline in verbal memory
      detectable in middle-aged, community-dwelling adults.

PMID- 23136262
TI  - Acute EEG findings in children with febrile status epilepticus: results of the
      FEBSTAT study.
AB  - OBJECTIVE: The FEBSTAT (Consequences of Prolonged Febrile Seizures) study is
      prospectively addressing the relationships among serial EEG, MRI, and clinical
      follow-up in a cohort of children followed from the time of presentation with
      febrile status epilepticus (FSE). METHODS: We recruited 199 children with FSE
      within 72 hours of presentation. Children underwent a detailed history, physical
      examination, MRI, and EEG within 72 hours. All EEGs were read by 2 teams and then
      conferenced. Associations with abnormal EEG were determined using logistic
      regression. Interrater reliability was assessed using the kappa statistic.
      RESULTS: Of the 199 EEGs, 90 (45.2%) were abnormal with the most common
      abnormality being focal slowing (n = 47) or attenuation (n = 25); these were
      maximal over the temporal areas in almost all cases. Epileptiform abnormalities
      were present in 13 EEGs (6.5%). In adjusted analysis, the odds of focal slowing
      were significantly increased by focal FSE (odds ratio [OR] = 5.08) and
      hippocampal T2 signal abnormality (OR = 3.50) and significantly decreased with
      high peak temperature (OR = 0.18). Focal EEG attenuation was also associated with
      hippocampal T2 signal abnormality (OR = 3.3). CONCLUSIONS: Focal EEG slowing or
      attenuation are present in EEGs obtained within 72 hours of FSE in a substantial
      proportion of children and are highly associated with MRI evidence of acute
      hippocampal injury. These findings may be a sensitive and readily obtainable
      marker of acute injury associated with FSE.

PMID- 23136263
TI  - Positional central apnea and vascular medullary compression.
AB  - A 66-year-old man with hypertension presented with complaints of excessive
      daytime sleepiness (Epworth Sleepiness Score 14/24), dyspnea upon exertion, and
      episodes of noninjurious dream-enacting behavior. He reported tongue biting when
      sleeping in the right lateral decubitus position. Medications included atenolol
      12.5 mg, lovastatin 20 mg, doxazosin 2 mg, amlodipine 5 mg, isosorbide
      mononitrate 60 mg, and aspirin 81 mg. He denied headaches, visual changes,
      dysarthria, dysphagia, or localized weakness. He denied use of alcohol, tobacco,
      or drugs.

PMID- 23136264
TI  - Evidence-based guideline update: steroids and antivirals for Bell palsy: report
      of the Guideline Development Subcommittee of the American Academy of Neurology.
AB  - OBJECTIVE: To review evidence published since the 2001 American Academy of
      Neurology (AAN) practice parameter regarding the effectiveness, safety, and
      tolerability of steroids and antiviral agents for Bell palsy. METHODS: We
      searched Medline and the Cochrane Database of Controlled Clinical Trials for
      studies published since January 2000 that compared facial functional outcomes in
      patients with Bell palsy receiving steroids/antivirals with patients not
      receiving these medications. We graded each study (Class I-IV) using the AAN
      therapeutic classification of evidence scheme. We compared the proportion of
      patients recovering facial function in the treated group with the proportion of
      patients recovering facial function in the control group. RESULTS: Nine studies
      published since June 2000 on patients with Bell palsy receiving
      steroids/antiviral agents were identified. Two of these studies were rated Class
      I because of high methodologic quality. CONCLUSIONS AND RECOMMENDATIONS: For
      patients with new-onset Bell palsy, steroids are highly likely to be effective
      and should be offered to increase the probability of recovery of facial nerve
      function (2 Class I studies, Level A) (risk difference 12.8%-15%). For patients
      with new-onset Bell palsy, antiviral agents in combination with steroids do not
      increase the probability of facial functional recovery by >7%. Because of the
      possibility of a modest increase in recovery, patients might be offered
      antivirals (in addition to steroids) (Level C). Patients offered antivirals
      should be counseled that a benefit from antivirals has not been established, and,
      if there is a benefit, it is likely that it is modest at best.

PMID- 23136266
TI  - Thank you . . .

PMID- 23136265
TI  - Atypical manifestations and poor outcome of herpes simplex encephalitis in the
      immunocompromised.
AB  - OBJECTIVE: To characterize clinical features, neuroimaging, and outcomes of
      herpes simplex encephalitis (HSE) in immunocompromised individuals. METHODS: We
      performed a retrospective case control review of patients diagnosed with HSE.
      Adult patients were dichotomized into immunocompromised (n = 14) and
      immunocompetent groups (n = 15). RESULTS: Fewer immunocompromised patients
      presented with prodromal symptoms and focal deficits. While the majority of CSF
      profiles in the immunocompromised patients were mononuclear cells predominant, 3
      had polymorphonuclear predominance and another 3 had normal profiles. MRI showed
      widespread cortical involvement, with brainstem or cerebellar involvement in
      some. Two immunocompromised patients had recurrent HSE. The immunosuppressed
      state was associated with a decrease in Karnofsky Performance Status Scale (KPSS)
      score of 23.1 (p = 0.018). Every 1-day delay in initiation of acyclovir was
      associated with a decrease in KPSS of 10.2 (p = 0.002), and every 10 cell/mm(3)
      increase of CSF leukocytosis was associated with an increase in KPSS of 0.7 (p =
      0.009). Mortality rate was 6 times higher in the immunocompromised patients.
      CONCLUSIONS: Immunocompromised states may predispose to HSE with atypical
      clinical and neuroradiologic features. Immunocompromised individuals with HSE
      have significantly worse outcomes and mortality. Early diagnosis and treatment is
      associated with improved outcome. The findings are particularly important in
      light of the increasing use of potent immunosuppressive and immunomodulatory
      therapies.

PMID- 23136267
TI  - Techniques of arthrodesis in the foot and ankle.

PMID- 23136268
TI  - Perceived price sensitivity by ethnicity and smoking frequency among California
      Hispanic and non-Hispanic white smokers.
AB  - OBJECTIVES: Little is currently known about price sensitivity across ethnic
      groups as well as for non-daily smokers. To address this issue, this study
      compared perceived price sensitivity across smoking status (daily and non-daily)
      and within ethnicity (Hispanic and non-Hispanic White) in a recent representative
      population survey of California smokers. METHODS: This study employed data from
      the 2008 California Tobacco Survey (CTS), a large population-based random-digit
      dialed telephone survey. Participants were 1,777 non-Hispanic White and 450
      Hispanic respondents who had smoked at least 100 cigarettes and currently smoked
      daily or on some days. RESULTS: Differences in perceived price sensitivity were
      found by ethnicity when controlling for age, gender, and cigarette consumption.
      Comparisons across ethnic groups indicated that Hispanic smokers, in general,
      have more price-sensitive perceptions than non-Hispanic White smokers. However,
      daily versus non-daily status had no effect on price sensitivity when controlling
      for cigarette quantity. CONCLUSIONS: These findings indicate that pricing
      increases may be differentially influential for Hispanic compared with non
      Hispanic White smokers across smoking status categories.

PMID- 23136269
TI  - Individual, social, and environmental factors associated with support for smoke
      free housing policies among subsidized multiunit housing tenants.
AB  - INTRODUCTION: Mandatory smoke-free policies in subsidized, multiunit housing
      (MUH) may decrease secondhand smoke exposure in households with the highest rates
      of exposure. Ideally, policies should be based on a strong understanding of
      factors affecting support for smoke-free policies in the target population to
      maximize effectiveness. METHODS: A face-to-face survey was conducted from August
      to October 2011 using a stratified random sample of private subsidized housing
      units in Columbus, OH, without an existing smoke-free policy (n = 301, 64%
      response rate). Lease holders were asked to report individual, social, and
      environmental factors hypothesized to be related to support for smoke-free
      policies. Multiple logistic regression models were used to identify factors
      independently associated with policy support. RESULTS: Most tenants supported
      smoke-free policies in common areas (82.7%), half supported policies inside units
      (54.5%), and one third supported a ban outside the building (36.3%). Support for
      smoke-free policies in units and outdoors was more common among nonsmokers than
      smokers (71.5% vs. 35.7%, p < .001 and 46.2% vs. 25.4%, p < .001, respectively).
      Several individual and social, but no environmental, factors were independently
      associated with policy support. Smokers who intended to quit within 6 months or
      less were more likely than other smokers to support in-unit policies (45.3% vs.
      21.1%; p = .003). CONCLUSIONS: More than half of subsidized MUH tenants supported
      smoke-free policies inside their units. Strategies to address individual- and
      social-level barriers to behavior change should be implemented in parallel with
      smoke-free policies. Policies should be evaluated with objective measures to
      determine their effectiveness.

PMID- 23136270
TI  - Special CCM Supplement in the American Journal of Tropical Medicine and Hygiene.
      Preface.

PMID- 23136271
TI  - Introduction to a special supplement: Evidence for the implementation, effects,
      and impact of the integrated community case management strategy to treat
      childhood infection.

PMID- 23136272
TI  - World Health Organization/United Nations Children's Fund joint statement on
      integrated community case management: an equity-focused strategy to improve
      access to essential treatment services for children.
AB  - This statement presents the latest evidence for integrated community case
      management of childhood illness, describes the necessary program elements and
      support tools for effective implementation, and lays out actions that countries
      and partners can take to support the implementation of integrated community case
      management at scale.

PMID- 23136273
TI  - Impact of community management of fever (using antimalarials with or without
      antibiotics) on childhood mortality: a cluster-randomized controlled trial in
      Ghana.
AB  - Malaria and pneumonia are leading causes of childhood mortality. Home Management
      of fever as Malaria (HMM) enables presumptive treatment with antimalarial drugs
      but excludes pneumonia. We aimed to evaluate the impact of adding an antibiotic,
      amoxicillin (AMX) to an antimalarial, artesunate amodiaquine (AAQ + AMX) for
      treating fever among children 2-59 months of age within the HMM strategy on all
      cause mortality. In a stepped-wedge cluster-randomized, open trial, children 2-59
      months of age with fever treated with AAQ or AAQ + AMX within HMM were compared
      with standard care. Mortality reduced significantly by 30% (rate ratio [RR] =
      0.70, 95% confidence interval [CI] = 0.53-0.92, P = 0.011) in AAQ clusters and by
      44% (RR = 0.56, 95% CI = 0.41-0.76, P = 0.011) in AAQ + AMX clusters compared
      with control clusters. The 21% mortality reduction between AAQ and AAQ + AMX (RR
      = 0.79, 95% CI = 0.56-1.12, P = 0.195) was however not statistically significant.
      Community fever management with antimalarials significantly reduces under-five
      mortality. Given the lower mortality trend, adding an antibiotic is more
      beneficial.

PMID- 23136274
TI  - Integrated community case management of fever in children under five using rapid
      diagnostic tests and respiratory rate counting: a multi-country cluster
      randomized trial.
AB  - Evidence on the impact of using diagnostic tests in community case management of
      febrile children is limited. This effectiveness trial conducted in Burkina Faso,
      Ghana, and Uganda, compared a diagnostic and treatment package for malaria and
      pneumonia with presumptive treatment with anti-malarial drugs; artemisinin
      combination therapy (ACT). We enrolled 4,216 febrile children between 4 and 59
      months of age in 2009-2010. Compliance with the malaria rapid diagnostic test
      (RDT) results was high in the intervention arm across the three countries, with
      only 4.9% (17 of 344) of RDT-negative children prescribed an ACT. Antibiotic
      overuse was more common: 0.9% (4 of 446) in Uganda, 38.5% (114 of 296) in Burkina
      Faso, and 44.6% (197 of 442) in Ghana. Fever clearance was high in both
      intervention and control arms at both Day 3 (97.8% versus 96.9%, P = 0.17) and
      Day 7 (99.2% versus 98.8%, P = 0.17). The use of diagnostic tests limits overuse
      of ACTs. Its impact on antibiotic overuse and on fever clearance is uncertain.

PMID- 23136275
TI  - Use of community health workers for management of malaria and pneumonia in urban
      and rural areas in eastern Uganda.
AB  - Use of community health workers (CHWs) has been implemented the same way in urban
      and rural areas despite differences in availability of health providers and
      sociodemographic characteristics. A household survey was conducted in rural and
      urban areas in eastern Uganda, and all children who were febrile in the previous
      two weeks were assessed for their symptoms, treatment received at home, and when
      and where they first went for treatment. Rural children were more likely to use
      CHWs than urban children. Urban children received outside treatment more
      promptly, and used herbs at home less. Symptoms and proportion of children being
      taken out for treatment were similar. Children from the poorest households used
      CHWs less and private providers more than the middle quintiles. Drug shops and
      private clinics should be included in the community case management to cater for
      the poorest in rural areas and persons in urban areas.

PMID- 23136276
TI  - Increased use of community medicine distributors and rational use of drugs in
      children less than five years of age in Uganda caused by integrated community
      case management of fever.
AB  - We compared use of community medicine distributors (CMDs) and drug use under
      integrated community case management and home-based management strategies in
      children 6-59 months of age in eastern Uganda. A cross-sectional study with 1,095
      children was nested in a cluster randomized trial with integrated community case
      management (CMDs treating malaria and pneumonia) as the intervention and home
      based management (CMDs treating only malaria) as the control. Care-seeking from
      CMDs was higher in intervention areas (31%) than in control areas (22%; P =
      0.01). Prompt and appropriate treatment of malaria was higher in intervention
      areas (18%) than in control areas (12%; P = 0.03) and among CMD users (37%) than
      other health providers (9%). The mean number of drugs among CMD users compared
      with other health providers was 1.6 versus 2.4 in intervention areas and 1.4
      versus 2.3 in control areas. Use of CMDs was low. However, integrated community
      case management of childhood illnesses increased use of CMDs and rational drug
      use.

PMID- 23136277
TI  - Introduction of newborn care within integrated community case management in
      Uganda.
AB  - Uganda's Ministry of Health, together with partners, has introduced integrated
      community case management (iCCM) for children under 5 years. We assessed how the
      iCCM program addresses newborn care in three midwestern districts through
      document reviews, structured interviews, and focus group discussions with village
      health team (VHT) members trained in iCCM, caregivers, and other stakeholders.
      Almost all VHT members reported that they refer sick newborns to facilities and
      could identify at least three newborn danger signs. However, they did not
      identify the most important clinical indicators of severe illness. The extent of
      compliance with newborn referral and quality of care for newborns at facilities
      is not clear. Overall iCCM is perceived as beneficial, but caregivers, VHTs, and
      health workers want to do more for sick babies at facilities and in communities.
      Additional research is needed to assess the ability of VHTs to identify newborn
      danger signs, referral compliance, and quality of newborn treatment at
      facilities.

PMID- 23136278
TI  - Scaling up integrated community case management of childhood illness: update from
      Malawi.
AB  - The Government of Malawi (GoM) initiated activities to deliver treatment of
      common childhood illnesses (suspected pneumonia, fever/suspected malaria, and
      diarrhea) in the community in 2008. The service providers are Health Surveillance
      Assistants (HSAs), and they are posted nationwide to serve communities at a ratio
      of 1 to 1,000 population. The GoM targeted the establishment of 3,452 village
      health clinics (VHCs) in hard-to-reach areas by 2011. By September of 2011, 3,296
      HSAs had received training in integrated case management of childhood illness,
      and 2,709 VHCs were functional. An assessment has shown that HSAs are able to
      treat sick children with quality similar to the quality provided in fixed
      facilities. Monitoring data also suggest that communities are using the sick
      child services. We summarize factors that have facilitated the scale up of
      integrated community case management of children in Malawi and address
      challenges, such as ensuring a steady supply of medicines and supportive
      supervision.

PMID- 23136279
TI  - Health workers' and managers' perceptions of the integrated community case
      management program for childhood illness in Malawi: the importance of expanding
      access to child health services.
AB  - Community case management (CCM) is a promising task-shifting strategy for
      expanding treatment of childhood illness that is increasingly adopted by low
      income countries. Its success depends in part on how the strategy is perceived by
      those responsible for its implementation. This study uses qualitative methods to
      explore health workers' and managers' perceptions about CCM provided by health
      surveillance assistants (HSAs) during the program's first year in Malawi.
      Managers and HSAs agreed that CCM contributed beneficially by expanding access to
      the underserved and reducing caseloads at health facilities. Managers differed
      among themselves in their endorsements of CCM, most offered constrained
      endorsement, and a few had stronger justifications for CCM. In addition, HSAs
      uniformly wanted continued expansion of their clinical role, while managers
      preferred to view CCM as a limited mandate. The HSAs also reported motivating
      factors and frustrations related to system constraints and community pressures
      related to CCM. The impact of CCM on motivation and workload of HSAs is noted and
      deserves further attention.

PMID- 23136280
TI  - A health systems approach to integrated community case management of childhood
      illness: methods and tools.
AB  - Integrated community case management (iCCM) of childhood illness is an
      increasingly popular strategy to expand life-saving health services to
      underserved communities. However, community health approaches vary widely across
      countries and do not always distribute resources evenly across local health
      systems. We present a harmonized framework, developed through interagency
      consultation and review, which supports the design of CCM by using a systems
      approach. To verify that the framework produces results, we also suggest a list
      of complementary indicators, including nine global metrics, and a menu of 39
      country-specific measures. When used by program managers and evaluators, we
      propose that the framework and indicators can facilitate the design,
      implementation, and evaluation of community case management.

PMID- 23136281
TI  - Beyond distance: an approach to measure effective access to case management for
      sick children in Africa.
AB  - Health planners commonly use geographic proximity to define access to health
      services. However, effective access to case management requires reliable access
      to a trained, supplied provider. We defined effective access as the proportion of
      the study population with geographic access, corrected for other barriers,
      staffing patterns, and medicine availability. We measured effective access
      through a cross-sectional survey of 32 health facilities in Malawi, Mali, and
      Zambia and modeled the potential contribution of community case management (CCM).
      The population living within Ministry of Health (MOH)-defined geographic access
      was 43% overall (range = 18-52%), but effective access was only 14% overall
      (range = 9-17%). Implementing CCM as per MOH plans increased geographic access to
      63-90% and effective access to 30-57%. Access to case management is much worse
      than typically estimated by distance. The CCM increases access dramatically,
      again if providers are available and supplied, and should be considered even for
      those within MOH-defined access areas.

PMID- 23136282
TI  - Community health workers providing government community case management for child
      survival in sub-Saharan Africa: who are they and what are they expected to do?
AB  - We describe community health workers (CHWs) in government community case
      management (CCM) programs for child survival across sub-Saharan Africa. In sub
      Saharan Africa, 91% of 44 United Nations Children's Fund (UNICEF) offices
      responded to a cross-sectional survey in 2010. Frequencies describe CHW profiles
      and activities in government CCM programs (N = 29). Although a few programs paid
      CHWs a salary or conversely, rewarded CHWs purely on a non-financial basis, most
      programs combined financial and non-financial incentives and had training for 1
      week. Not all programs allowed CHWs to provide zinc, use timers, dispense
      antibiotics, or use rapid diagnostic tests. Many CHWs undertake health promotion,
      but fewer CHWs provide soap, water treatment products, indoor residual spraying,
      or ready-to-use therapeutic foods. For newborn care, very few promote kangaroo
      care, and they do not provide antibiotics or resuscitation. Even if CHWs are as
      varied as the health systems in which they work, more work must be done in terms
      of the design and implementation of the CHW programs for them to realize their
      potential.

PMID- 23136283
TI  - Private sector drug shops in integrated community case management of malaria,
      pneumonia, and diarrhea in children in Uganda.
AB  - We conducted a survey involving 1,604 households to determine community care
      seeking patterns and 163 exit interviews to determine appropriateness of
      treatment of common childhood illnesses at private sector drug shops in two rural
      districts of Uganda. Of children sick within the last 2 weeks, 496 (53.1%)
      children first sought treatment in the private sector versus 154 (16.5%) children
      first sought treatment in a government health facility. Only 15 (10.3%) febrile
      children treated at drug shops received appropriate treatment for malaria. Five
      (15.6%) children with both cough and fast breathing received amoxicillin,
      although no children received treatment for 5-7 days. Similarly, only 8 (14.3%)
      children with diarrhea received oral rehydration salts, but none received zinc
      tablets. Management of common childhood illness at private sector drug shops in
      rural Uganda is largely inappropriate. There is urgent need to improve the
      standard of care at drug shops for common childhood illness through public
      private partnerships.

PMID- 23136284
TI  - Community acceptability and adoption of integrated community case management in
      Uganda.
AB  - Integrated community case management (iCCM) is a recommended strategy to curb
      child mortality. Drawing on diffusion of innovations (DOIs), the acceptability
      and adoption of iCCM were qualitatively explored. Data from focus group
      discussions and interviews with community members, community health workers
      (CHWs), and supervisors conducted in seven communities were analyzed using
      content analysis. Perceived relative advantage and compatibility of the program
      with sociocultural beliefs and healthcare expectations of the communities
      positively affected acceptability and adoption of iCCM. The degree of stringency,
      quality, and cost of access to healthcare were crucial to adoption. Failure of
      the health system to secure regular drug supplies, monetary support, and safe
      referrals globally hindered adoption. Individual CHW characteristics like
      undesired behavior, demotivation, and lack of reciprocated trust deterred
      adoption in some areas. Optimal functioning of iCCM programs will require
      community sensitization and targeted health systems strengthening to enhance
      observable program benefits like reduced child mortality.

PMID- 23136285
TI  - Impact of integrated community case management on health-seeking behavior in
      rural Zambia.
AB  - Provision of integrated community case management (iCCM) for common childhood
      illnesses by community health workers (CHWs) represents an increasingly common
      strategy for reducing childhood morbidity and mortality. We sought to assess how
      iCCM availability influenced care-seeking behavior. In areas where two different
      iCCM approaches were implemented, we conducted baseline and post-study household
      surveys on healthcare-seeking practices among women who were caring for children
      <= 5 years in their homes. For children presenting with fever, there was an
      increase in care sought from CHWs and a decrease in care sought at formal health
      centers between baseline and post-study periods. For children with
      fast/difficulty breathing, an increase in care sought from CHWs was only noted in
      areas where CHWs were trained and supplied with amoxicillin to treat non-severe
      pneumonia. These findings suggest that iCCM access influences local care-seeking
      practices and reduces workload at primary health centers.

PMID- 23136286
TI  - Interventions to improve motivation and retention of community health workers
      delivering integrated community case management (iCCM): stakeholder perceptions
      and priorities.
AB  - Despite resurgence in the use of community health workers (CHWs) in the delivery
      of community case management of childhood illnesses, a paucity of evidence for
      effective strategies to address key constraints of worker motivation and
      retention endures. This work reports the results of semi-structured interviews
      with 15 international stakeholders, selected because of their experiences in CHW
      program implementation, to elicit their views on strategies that could increase
      CHW motivation and retention. Data were collected to identify potential
      interventions that could be tested through a randomized control trial. Suggested
      interventions were organized into thematic areas; cross-cutting approaches,
      recruitment, training, supervision, incentives, community involvement and
      ownership, information and data management, and mHealth. The priority
      interventions of stakeholders correspond to key areas of the work motivation and
      CHW literature. Combined, they potentially provide useful insight for programmers
      engaging in further enquiry into the most locally relevant, acceptable, and
      evidence-based interventions.

PMID- 23136287
TI  - Factors affecting availability of essential medicines among community health
      workers in Ethiopia, Malawi, and Rwanda: solving the last mile puzzle.
AB  - To understand how supply chain factors affect product availability at the
      community level, the Improving Supply Chains for Community Case Management of
      Pneumonia and Other Common Diseases of Childhood Project developed a theory of
      change (TOC) framework for gathering, organizing, and interpreting evidence about
      supply constraints to community case management (CCM). Baseline assessments in
      Ethiopia, Malawi, and Rwanda conducted in 2010 provided information on the
      strengths and weaknesses of existing CCM supply chains for five main products:
      antibiotics for pneumonia, oral rehydration solution, ready to use therapeutic
      food, zinc, and artemether/lumefantrine. The assessments tested the strength and
      validity of causal pathways identified in the TOC that were believed to influence
      availability of CCM products among community health workers (CHWs) for treating
      common childhood illnesses. Results of the assessments showed product
      availability to be weak in each country, with more than half of CHWs stocked out
      of at least one tracer product on the day of the assessment. This report will
      focus on the findings related to three key preconditions of the TOC and how these
      were used to inform the design of the CCM supply chain improvement strategy in
      each country. The three key preconditions include product availability at CHW
      resupply points, supply chain knowledge and capacity among CHWs and their
      supervisors, and availability of appropriate transportation.

PMID- 23136288
TI  - Comparison of methods for assessing quality of care for community case management
      of sick children: an application with community health workers in Malawi.
AB  - Direct observation (DO) with re-examination (RE) by a skilled clinician is a
      rigorous method for assessing health worker performance, but is not always
      feasible. We assessed the performance of 131 community health workers in Malawi
      in community case management of sick children with cough and fast breathing,
      fever, and diarrhea. We compared estimates of correct treatment measured through
      DO with RE (n = 382 cases) to DO only (n = 382 cases), register review (n = 1,219
      cases), and case scenarios (n = 917 cases). Estimates of correct treatment of
      uncomplicated fever and diarrhea measured through DO only, register review, and
      case scenarios were within 9 percentage points of DO with RE estimates, while
      estimates for uncomplicated cough and fast breathing, and severe illness were
      substantially higher than DO with RE (12-51 percentage points above the
      estimate). Those planning for community health worker assessments in community
      case management can use these results to make an informed choice of methods on
      the basis of their objectives and the local context.

PMID- 23136289
TI  - Household costs for treatment of severe pneumonia in Pakistan.
AB  - Current World Health Organization (WHO) guidelines for severe pneumonia treatment
      of under-5 children recommend hospital referral. However, high treatment cost is
      a major barrier for communities. We compared household costs for referred cases
      with management by lady health workers (LHWs) using oral antibiotics. This study
      was nested within a cluster randomized trial in Haripur, Pakistan. Data on direct
      and indirect costs were collected through interviews and record reviews in the 14
      intervention and 14 control clusters. The average household cost/case for a LHW
      managed case was $1.46 compared with $7.60 for referred cases. When the cost of
      antibiotics provided by the LHW program was excluded from the estimates, the
      cost/case came to $0.25 and $7.51 for the community managed and referred cases,
      respectively, a 30-fold difference. Expanding severe pneumonia treatment with
      oral amoxicillin to community level could significantly reduce household costs
      and improve access to the underprivileged population, preventing many child
      deaths.

PMID- 23136290
TI  - Insights from community case management data in six sub-Saharan African
      countries.
AB  - There is strong research evidence that community case management (CCM) programs
      can significantly reduce mortality. There is less evidence, however, on how to
      implement CCM effectively either from research or regular program data. We
      analyzed monitoring data from CCM programs supported by the International Rescue
      Committee (IRC), covering over 2 million treatments provided from 2004 to 2011 in
      six countries by 12,181 community health workers (CHWs). Our analysis yielded
      several findings of direct relevance to planners and managers. CCM programs seem
      to increase access to treatment, although diarrhea coverage remains low. In one
      country, the size of the catchment area was correlated with use, and increased
      supervision was temporally and strongly associated with improved quality.
      Planners should use routine data to guide CCM program planning. Programs should
      treat all three conditions from the outset. Other priorities should include use
      of diarrhea treatment and insurance of adequate supervision.

PMID- 23136291
TI  - Integrated community case management: next steps in addressing the implementation
      research agenda.

PMID- 23136294
TI  - DNA microarray reveals that high proportions of human blastocysts from women of
      advanced maternal age are aneuploid and mosaic.
AB  - Trophectoderm (TE) biopsy and DNA microarray have become the new technologies for
      preimplantation genetic diagnosis in humans. In this study, we comprehensively
      examined aneuploid formation in human blastocysts produced in vitro with
      microarray and investigated the clinical outcome after transfer of euploid
      embryos. Biopsied cells from either TE or inner cell mass (ICM) were processed
      for microarray to examine the errors in 23 pairs of chromosomes and the
      consistency between TE and ICM. It was found that 56.6% of blastocysts were
      aneuploid. Further analysis indicated that 62.3% of aneuploid blastocysts had
      single and 37.7% had multiple chromosomal abnormalities. Chromosome errors could
      occur in any chromosome, but errors in chromosome 21 accounted for the most
      (11.3%) among the 23 pairs of chromosomes. Transfer of array-screened blastocysts
      produced high pregnancy (70.2%) and implantation (63.5%) rates. Microarray of TE
      and ICM cells in the same blastocysts revealed that high proportions of aneuploid
      blastocysts (69.2%) were mosaic, including aneuploid TE and euploid ICM,
      inconsistent anomalies between ICM and TE, or euploid TE cells and aneuploid ICM
      in the same blastocyst. These results indicate that high proportions of human
      blastocysts produced in vitro from women of advanced maternal age are aneuploid
      and mosaic. Errors can occur in any of the 23 pairs of chromosomes in human
      blastocysts. Biopsy from TE in blastocysts does not exactly predict the
      chromosomal information in ICM if the embryos are aneuploid. Some mosaic
      blastocysts have euploid ICM, which may indicate important differentiate
      mechanism(s) of human preimplantation embryos.

PMID- 23136295
TI  - Chronic hypoxia differentially up-regulates protein kinase C-mediated ovine
      uterine arterial contraction via actin polymerization signaling in pregnancy.
AB  - Chronic hypoxia (CH) during pregnancy is associated with increased uterine
      vascular tone. The present study tested the hypothesis that CH up-regulates
      protein kinase C (PKC)-mediated actin polymerization, resulting in enhanced
      uterine vascular contraction in pregnancy. Uterine arteries were isolated from
      nonpregnant (NPUA) and near-term (~140 days of gestation) pregnant (PUA) sheep
      that had been maintained at sea level (~300 m) or exposed to high altitude (3801
      m) hypoxia for 110 days. In normoxic animals, the induced contractions by the PKC
      activator phorbol 12,13-dibutyrate (PDBu) were greater in NPUA than in PUA, which
      was abrogated by an actin polymerization inhibitor cytochalasin B (Cyto B). In
      hypoxic animals, PDBu-induced contractions were significantly increased in PUA
      but not in NPUA, which was inhibited by Cyto B. In contrast, neither pregnancy
      nor hypoxia affected Cyto B-mediated inhibition of norepinephrine (NE)-induced
      contractions. Prolonged ex vivo treatment of NPUA with 17beta-estradiol and
      progesterone significantly attenuated PDBu-induced actin polymerization and
      contractions, and the hormonal treatment did not alter the inhibitory effect of
      Cyto B on PDBu- or NE-induced contractions in either normoxic or hypoxic animals.
      2-(2-Amino-3-methoxyphenyl)-4H-1-benzopyran-4-one potentiated PDBu-mediated actin
      polymerization and enhanced PDBu-induced contractions of PUA in normoxic but not
      hypoxic animals, which was abrogated by Cyto B. The results suggest that chronic
      hypoxia during pregnancy causes attenuation of steroid hormone-mediated ERK1/2
      signaling and results in increased actin polymerization and uterine vascular
      tone, linking gestational hypoxia to aberrant uteroplacental circulation.

PMID- 23136296
TI  - EGF-like ligands mediate progesterone's anti-apoptotic action on macaque
      granulosa cells.
AB  - A local autocrine/paracrine role for progesterone is an absolute requirement for
      corpus luteum formation in primates. Despite this, the mechanism(s) remain
      obscure, although existing data suggest an anti-apoptotic action to be central.
      There are a limited number of progestin-regulated gene targets identified in the
      luteinizing primate follicle, suggesting that a small number of important genes
      may mediate progesterone action. Possible gene targets could be the epidermal
      growth factor (EGF) family members amphiregulin (AREG) and epiregulin (EREG).
      Using macaques undergoing controlled ovarian stimulation cycles, we show that the
      phosphorylation of EGF receptor (EGFR), ERK 1/2, and AKT increases 6 h after an
      ovulatory human chorionic gonadotropin (hCG) stimulus and remains activate
      through 24 h. Immunoreactive EREG and AREG ligands in the follicular fluid both
      increased in a time frame commensurate with EGFR phosphorylation. The mRNA
      expression of AREG and EREG in nonluteinized granulosa cells (NLGC) was induced
      in culture with hCG, an effect blocked by progesterone receptor (PGR)
      antagonists. Overexpression of PGR B in NLGC and treatment with a
      nonmetabolizable progestin did not increase either gene, indicating both
      progesterone and luteinizing hormone/CG are necessary. Addition of EGF and EGF
      like ligands did not promote steroidogenesis in vitro by granulosa cells in the
      presence of gonadotropin, but were able to partially reverse RU486-induced cell
      death. These data suggest that progesterone promotes the expression of AREG and
      EREG, which in turn maintain viability of luteinizing granulosa cells,
      representing one possible mechanism whereby progesterone promotes corpus luteum
      formation in the primate.

PMID- 23136298
TI  - SIRT6 is decreased with preterm labor and regulates key terminal effector
      pathways of human labor in fetal membranes.
AB  - Preterm birth is a major determinant of neonatal mortality and morbidity,
      affecting approximately one-third of preterm births as a result of prelabor
      rupturing of membranes. Infection and inflammation have strong causal links to
      preterm delivery, resulting in the activation of nuclear factor-kappaB (NFKB) and
      its downstream targets. Human sirtuin (SIRT) 6, which has ADP-ribosyl transferase
      and deacetylase activity, exhibits anti-inflammatory actions. The aims of this
      study were to determine the effect of 1) human preterm labor on SIRT6 expression
      in human gestational tissue and 2) the effect in primary amnion cells of SIRT6
      inhibition, using small interfering RNA (siRNA) on prolabor mediators. To
      determine the effect of human preterm labor on SIRT6 expression, human fetal
      membranes were collected from women at preterm at the time of Cesarean section
      (no labor; n = 9) and from women after spontaneous labor and delivery (n = 9).
      SIRT6 mRNA and protein expression were significantly lower in fetal membranes
      after spontaneous preterm labor. Transfection of primary amnion cells with SIRT6
      siRNA was associated with an increase in IL-1beta-induced proinflammatory
      cytokine gene expression and release (IL6, IL8, TNF [TNF-alpha]), cyclooxygenase
      ([COX]-2; official symbol PTGS2) expression and subsequent prostaglandin (PGE(2)
      and PGF(2alpha)) release, and MMP9 gene expression and release of pro-MMP9. To
      determine whether SIRT6 affects NFKB transcriptional activity, primary amnion
      cells were transfected with NFKB tagged with luciferase and stimulated with IL1B.
      As expected, IL1B induced NFKB transcriptional activity. However, when cells were
      also cotransfected with a vector expressing SIRT6, there was a decrease in NFKB
      transcriptional activity. In conclusion, SIRT6 plays a role in regulating the
      terminal effector pathways of human labor and delivery via the NFKB pathway.

PMID- 23136297
TI  - Computer-assisted annotation of murine Sertoli cell small RNA transcriptome.
AB  - Mammalian genomes encode a large number of small noncoding RNAs (sncRNAs) that
      play regulatory roles during development and adulthood by affecting gene
      expression. Several sncRNA species, including microRNAs (miRNAs), piwi
      interacting RNAs (piRNAs), endogenous small interfering RNAs (endo-siRNAs), and
      small nucleolar RNAs (snoRNAs), are abundantly expressed in the testis and
      required for normal testicular development and spermatogenesis. To evaluate
      global changes in sncRNA expression, the next-generation sequencing (NGS)-based
      sncRNA transcriptomic analysis has become routine, because it allows rapid
      determination of the small RNA transcriptome of a particular testicular cell
      type. However, annotation of small RNA NGS reads can be challenging due to the
      volume of reads obtained, which is usually in the millions. Therefore, we
      developed a computer-assisted sncRNA annotation protocol that could identify not
      only known sncRNAs but also previously uncharacterized ones. Using this protocol,
      we annotated NGS reads of a Sertoli cell sncRNA library, and we report to our
      knowledge the first comprehensive annotation of the sncRNA transcriptome of
      immature murine Sertoli cells. Moreover, the computer-assisted sncRNA annotation
      pipeline that we report is applicable for annotating NGS reads derived from other
      cell types and/or sequencing platforms.

PMID- 23136299
TI  - Maternally recruited DCP1A and DCP2 contribute to messenger RNA degradation
      during oocyte maturation and genome activation in mouse.
AB  - The oocyte-to-zygote transition entails transforming a highly differentiated
      oocyte into totipotent blastomeres and represents one of the earliest obstacles
      that must be successfully hurdled for continued development. Degradation of
      maternal mRNAs, which likely lies at the heart of this transition, is
      characterized by a transition from mRNA stability to instability during oocyte
      maturation. Although phosphorylation of the oocyte-specific RNA-binding protein
      MSY2 during maturation is implicated in making maternal mRNAs more susceptible to
      degradation, mechanisms underlying mRNA degradation during oocyte maturation
      remain poorly understood. We report that DCP1A and DCP2, proteins responsible for
      decapping mRNA, are encoded by maternal mRNAs recruited for translation during
      maturation via cytoplasmic polyadenylation elements located in their 3'
      untranslated regions. Both DCP1A and DCP2 are phosphorylated during maturation,
      with CDC2A being the kinase likely responsible for both, although MAPK may be
      involved in DCP1A phosphorylation. Inhibiting accumulation of DCP1A and DCP2 by
      RNA interference or morpholinos decreases not only degradation of mRNAs during
      meiotic maturation but also transcription of the zygotic genome. The results
      indicate that maternally recruited DCP1A and DCP2 are critical players in the
      transition from mRNA stability to instability during meiotic maturation and that
      proper maternal mRNA degradation must be successful to execute the oocyte-to
      zygote transition.

PMID- 23136300
TI  - Transcriptome fingerprint of bovine 2-cell stage blastomeres is directly
      correlated with the individual developmental competence of the corresponding
      sister blastomere.
AB  - To date, gene expression profiles of bovine preimplantation embryos have only
      been indirectly related to developmental potential due to the invasive nature of
      such procedures. This study sought to find a direct correlation between
      transcriptome fingerprint of blastomeres of bovine 2-cell stage embryos with
      developmental competence of the corresponding sister blastomeres. Isolated
      blastomeres were classified according to the sister blastomere's development into
      three groups: two groups displayed developmental incompetency, including those
      blastomeres whose corresponding sister blastomeres either stopped cleaving after
      separation (2CB) or were blocked after two additional cleavages before embryonic
      genome activation (8CB). In the third group were competent blastomeres, which
      were defined as those whose sister blastomeres developed to the blastocyst stage
      (BL). As a result, developmental capacity of corresponding sister blastomeres was
      highly similar. Microarray analysis revealed 77 genes to be commonly
      differentially regulated among competent and incompetent blastomeres as well as
      blocked blastomeres. Clustering of differentially expressed genes according to
      molecular functions and pathways revealed antioxidant activity, NRF2-mediated
      oxidative stress response, and oxidative phosphorylation to be the main
      ontologies affected. Expression levels of selected candidate genes were further
      characterized in an independent model for developmental competence based on the
      time of first cleavage postfertilization. Moreover, overall results of this study
      were confirmed by higher developmental rates and more beneficial expression of
      CAT and PRDX1 when cultured in an antioxidative environment. These results will
      help us to understand molecular mechanisms defining developmental destination of
      individual bovine preimplantation embryos.

PMID- 23136301
TI  - Developmental arrest and mouse antral not-surrounded nucleolus oocytes.
AB  - The antral compartment in the ovary consists of two populations of oocytes that
      differ by their ability to resume meiosis and to develop to the blastocyst stage.
      For reasons still not entirely clear, antral oocytes termed surrounded nucleolus
      (SN; 70% of the population of antral oocytes) develop to the blastocyst stage,
      whereas those called not-surrounded nucleolus (NSN) arrest at two cells. We
      profiled transcriptomic, proteomic, and morphological characteristics of antral
      oocytes and observed that NSN oocyte arrest is associated with lack of
      cytoplasmic lattices coincident with reduced expression of MATER and ribosomal
      proteins. Cytoplasmic lattices have been shown to store maternally derived mRNA
      and ribosomes in mammalian oocytes and embryos, and MATER has been shown to be
      required for cytoplasmic lattice formation. Thus, we isolated antral oocytes from
      a Mater(tm/tm) mouse and we observed that 84% of oocytes are of the NSN type. Our
      results provide the first molecular evidence to account for inability of NSN
      derived embryos to progress beyond the two-cell stage; these results may be
      relevant to naturally occurring preimplantation embryo demise in mammals.

PMID- 23136302
TI  - Nursing for 48 hours from birth supports porcine uterine gland development and
      endometrial cell compartment-specific gene expression.
AB  - The first 2 wk of neonatal life constitute a critical period for estrogen
      receptor alpha (ESR1)-dependent uterine adenogenesis in the pig. A relaxin
      receptor (RXFP1)-mediated, lactocrine-driven mechanism was proposed to explain
      how nursing could regulate endometrial ESR1 and related gene expression events
      associated with adenogenesis in the porcine neonate during this period. To
      determine effects of nursing on endometrial morphogenesis and cell compartment
      specific gene expression, gilts (n = 6-8/group) were assigned at birth to be
      either 1) nursed ad libitum for 48 h, 2) gavage fed milk replacer for 48 h, 3)
      nursed ad libitum to Postnatal Day (PND) 14, or 4) gavage fed milk replacer for
      48 h followed by ad libitum nursing to PND 14. Uteri were collected on PND 2 or
      PND 14. Endometrial histoarchitecture and both ESR1 and proliferating cell
      nuclear antigen (PCNA) labeling indexes (LIs) were evaluated. Laser
      microdissection was used to capture epithelium and stroma to evaluate treatment
      effects on cell compartment-specific ESR1, VEGFA, and RXFP1 expression.
      Imposition of a lactocrine-null state by milk replacer feeding for 48 h from
      birth retarded endometrial development and adenogenesis. Effects of replacer
      feeding, evident by PND 2, were marked by PND 14 when endometrial thickness,
      glandularity, and gland depth were reduced. Consistently, in lactocrine-null
      gilts, PCNA LI was reduced in glandular epithelium (GE) and stroma on PND 14,
      when epithelial ESR1 expression and ESR1 LI in GE were reduced and stromal VEGFA
      and RXFP1 expression increased. Results establish that lactocrine signaling
      effects morphogenetic changes in developing uterine tissues that may determine
      reproductive capacity later in life.

PMID- 23136303
TI  - Health behavior in ecological context.
AB  - Health is best understood within an ecological context. Accordingly, health
      promotion involves processes that foster supportive environments and healthful
      behavior. Thus, effective health promotion programs are typically multilevel,
      focusing not only on the population at risk but also on the environmental
      conditions that contribute so importantly to health and health behavior. Health
      behavior is important at each societal level. Arguably, accomplishment of health
      promotion goals at each societal level requires changes in the behavior of those
      who control or influence the health outcomes of interest. Recognition of three
      distinct types of health behavior can guide multilevel health promotion program
      planning. Personal-health behavior affects the health of the person who engages
      in that behavior. Health-related behavior includes actions taken by proximal
      others that directly affect the health of others, although usually not
      purposefully. Health-protective behavior is undertaken purposefully to foster the
      health of others. Regardless of the outcome of interest or societal level,
      similar health promotion processes can be employed to alter health behavior.

PMID- 23136304
TI  - Talking (or not) about family health history in families of Latino young adults.
AB  - Although individuals recognize the importance of knowing their family's health
      history for their own health, relatively few people (e.g., less than a third in
      one national survey) collect this type of information. This study examines the
      rates of family communication about family health history of cancer, and
      predictors of communication in a sample of English-speaking Latino young adults.
      A total of 224 Latino young adults completed a survey that included measures on
      family communication, cultural factors, religious commitment, and cancer worry.
      We found that few Latino young adults reported collecting information from their
      families for the purposes of creating a family health history (18%) or sharing
      information about hereditary cancer risk with family members (16%). In contrast,
      slightly more than half of the participants reported generally "talking with
      their mothers about their family's health history of cancer." Logistic regression
      results indicated that cancer worry (odds ratio [OR] = 2.31; 95% confidence
      interval [CI] = 1.08-4.93), being female (OR = 3.12; 95% CI = 1.02-8.08), and
      being older (OR = 1.33; 95% CI = 1.01-1.76) were associated with increased rates
      of collecting information from family members. In contrast, orientation to the
      Latino culture (OR = 2.81; 95% CI = 1.33-5.94) and religious commitment (OR =
      1.54; 95% CI = 1.02-2.32) were associated with increased rates of giving cancer
      information. Results highlight the need for prevention programs to help further
      general discussions about a family's history of cancer to more specific
      information related to family health history. 

PMID- 23136305
TI  - New developments in undergraduate education in public health: implications for
      health education and health promotion.
AB  - The article provides an overview of efforts to improve public health and health
      education training and on the potential use of Critical Component Elements (CCEs)
      for undergraduate health education programs toward more consistent quality
      assurance across programs. Considered in the context of the Galway Consensus
      Conference, the authors discuss the need for consistency in health education and
      public health quality assurance and curricular development. They discuss emerging
      quality assurance trends in relation to newly approved CCEs by the Association of
      Schools of Public Health after being developed by the Framing the Future Task
      Force: The Second 100 Years for Public Health. The CCE development process is
      discussed including its consideration as a tool program, which can be used to
      develop or refine undergraduate health education professional preparation
      programs. The authors suggest that CCEs should be "cross-walked" against existing
      health education undergraduate-level competencies. The authors conclude that CCEs
      may serve the long-term health education goal of accreditation for undergraduate
      health education and promote the tradition of strong undergraduate health
      education within a broader framework of public health and health promotion.

PMID- 23136306
TI  - Galway revisited: tracking global progress in core competencies and quality
      assurance for health education and health promotion.

PMID- 23136307
TI  - Effect of temperament and prolonged transportation on endocrine and functional
      variables in young beef bulls.
AB  - The purpose of this study was to evaluate the effect of prolonged transportation
      on adrenocorticotropic hormone (ACTH), cortisol, total and free triiodothyronine
      (T(3), fT(3)) and thyroxine (T(4), fT(4)) concentrations, and functional
      variables (heart rate (HR), respiratory rate (RR) and rectal temperature (RT)) in
      calm and temperamental Limousin young beef bulls. Exit velocity measurement was
      used to classify bulls' temperament as calm (group I: consisted of eight slowest
      bulls) and temperamental (group II: consisted of five fastest bulls). Calm
      subjects showed an increase of ACTH (P<0.05) and T(4) (P<0.01) concentrations
      after transportation compared with before transportation values. Temperamental
      subjects showed higher ACTH (P<0.01) concentrations before transportation, and
      lower T(4) (P<0.05) and fT(4) (P<0.001) concentrations after transportation than
      calm subjects. Related to functional variables, temperamental young beef bulls
      showed a decrease of RT (P<0.05) after transportation compared with before
      values, higher RT (P<0.001) before transportation, and higher HR (P<0.001) and RR
      (P<0.01) after transportation than calm subjects. Data obtained suggest that
      longer periods of transportation could minimise the magnitude and duration of the
      endocrine and functional responses to stress of young beef bulls; such responses
      probably decrease or disappear during transport, in accordance with animal
      temperament.

PMID- 23136308
TI  - Steroid diffusion into the navicular bursa occurs in horses affected by palmar
      foot pain.
AB  - Palmar foot pain is frequently treated by steroid injections into the distal
      interphalangeal joint (DIPJ) in the anticipation that the steroid will diffuse to
      the navicular bursa and palmar foot structures. The object of this study was to
      determine if triamcinolone acetonide (TA) would in fact be able to locally
      diffuse from the DIPJ into the navicular bursa in horses affected by palmar foot
      pain. Both forelimb DIPJs (nine horses) were injected with 10 mg of TA. Navicular
      bursa fluid samples, both forelimb and one hind limb (systemic control), were
      analysed for TA with high-performance liquid chromatography/tandem mass
      spectrometry (HPLC-MS/MS) six hours later. Foot radiographs were graded (0-4) on
      severity of changes. Forelimb navicular bursa TA concentrations (mean+/-sd
      log(10), 3.20+/-0.56) were significantly higher than systemic control
      concentrations (mean+/-sd log(10), 1.89+/-0.3) (P<0.0001). Horses with a
      radiographic grade of >2 were four times as likely to have TA log(10)
      concentrations less than 3.2 (158.49 ng/ml). TA locally diffused from the DIPJ
      into the navicular bursa in horses affected by palmar foot pain; TA
      concentrations decreased as radiographic severity increased.

PMID- 23136309
TI  - Efficacy of in-feed medication with chlortetracycline in a farrow-to-finish herd
      against a clinical outbreak of respiratory disease in fattening pigs.
AB  - The efficacy of chlortetracycline (CTC) in-feed medication to treat pigs with
      clinical respiratory disease was investigated in a farrow-to-finish pig herd
      infected with Mycoplasma hyopneumoniae, and with clinical respiratory disease in
      growing pigs. In total, 533 pigs were included. The animals were vaccinated
      against M hyopneumoniae and porcine circovirus type 2 at weaning. At onset of
      clinical respiratory disease, they were randomly allocated to one of the
      following treatment groups: chlortetracycline 1 (CTC1) (two consecutive weeks,
      500 ppm), chlortetracycline 2 (CTC2) (two non-consecutive weeks, with a non
      medicated week interval in between, 500 ppm) or tylosin (T) (three consecutive
      weeks, 100 ppm). Performance (daily weight gain, feed conversion ratio),
      pneumonia lesions at slaughter and clinical parameters (respiratory disease
      score) were assessed. Only numeric differences in favour of the CTC2 group were
      obtained for the performance and the clinical parameters. The prevalence of
      pneumonia lesions was 20.5, 13.1 and 23.0 per cent (P<0.05) for the CTC1, CTC2
      and T groups, respectively. The study demonstrated that CTC, when administered at
      onset of clinical respiratory disease via the feed at a dose of 500 ppm during
      two alternative weeks, was able to decrease the prevalence of pneumonia lesions,
      and numerically reduce performance losses and clinical signs.

PMID- 23136310
TI  - Prostate cancer decision-making, health services, and the family physician
      workforce.
AB  - Does untreated cancer equal death? Does having a registered nurse versus a
      licensed practical nurse versus a medical assistant affect diabetes quality
      outcomes? Do physicians caring for stressed patients experience vicarious
      traumatic stress? Oregon presents an operationalized definition of a patient
      centered medical home for their state. Lots of important clinical topics in
      family medicine--adult attention deficit disorder office questionnaire; Bell
      palsy; cancer screening and treatment decisions; lubrication during Papanicolaou
      testing; changes in maternity care training by residencies; changing prescribing
      patterns for thiazide diuretics; and night sweats remain a mystery.

PMID- 23136311
TI  - Supporting physicians who work in challenging contexts: a role for the academic
      health center.
AB  - Physicians who work in challenging contexts such as remote rural locations or
      with special populations may need support in persevering in their positions and
      also may suffer vicarious trauma through their work. Academic health centers may
      be in a position to provide much needed support to these physicians through
      focused continuing medical education, faculty development, practice-based
      research networks, and other means.

PMID- 23136312
TI  - More house calls by fewer physicians.

PMID- 23136313
TI  - Engagement of family physicians in Maintenance of Certification remains high.
AB  - Maintenance of Certification for Family Physicians was created to enhance the
      quality of care delivered by family physicians but risked decreasing their
      engagement due to the increased burden of meeting additional requirements to
      remain board-certified. Participation by family physicians in Maintenance of
      Certification remains higher than predicted.

PMID- 23136314
TI  - Patient perspective on watchful waiting/active surveillance for localized
      prostate cancer.
AB  - OBJECTIVE: To describe prostate cancer treatment decision making, focusing on
      knowledge and attitudes toward observation, known as watchful waiting (WW) or
      active surveillance (AS), and reasons for not choosing WW/AS. METHODS:
      Semistructured in-person interviews were conducted with 21 men (14 black; 7
      white) with recently diagnosed localized prostate cancer. RESULTS: All cancers
      were detected by prostate-specific antigen screening; 14 men had low-risk
      disease. Nineteen chose surgery or radiation treatment. The majority wanted to
      "get rid of" or "cure" the cancer by undergoing aggressive therapy, even with
      awareness of the potential for significant side effects. Most men seemed unaware
      of the uncertainty/controversies that aggressive treatment may not cure their
      cancer or improve their survival. Limited knowledge about WW/AS was common, and
      few remembered WW/AS being presented as a viable option. Rather, many men
      perceived it as "doing nothing." Some men, who initially were inclined toward
      WW/AS, yielded to pressure from family, physicians, or both to choose aggressive
      treatment. Lack of physician support was a significant barrier to WW/AS.
      CONCLUSIONS: The observational strategy (WW/AS) was not viewed as a reasonable
      approach, even for those with low-risk cancer. The desire for aggressive therapy
      may reflect the complex psychology associated with receiving a diagnosis of
      cancer and the limited supportive counseling received. Further efforts to better
      understand and educate patients and physicians may help men make informed and
      appropriate treatment decisions to maximize quality of life without compromising
      survival.

PMID- 23136315
TI  - Physician-patient colorectal cancer screening discussions by physicians'
      screening rates.
AB  - BACKGROUND: Most physicians report routinely recommending colorectal cancer (CRC)
      screening, but many eligible patients are not screened. To better understand this
      finding, we explored the relationship between the content of hypothetical patient
      physician CRC screening discussions and CRC screening rates in physicians'
      practices. METHODS: Semistructured interviews, including role-playing, with 24
      primary care physicians explored their CRC screening approach with average-risk
      patients. Qualitative analysis examined physician-reported components of the CRC
      screening discussion, then compared findings between physicians with high (>=60%,
      n = 16) and low (<=45%, n = 8) CRC screening rates (based on HEDIS criteria). We
      conducted no statistical tests because of the small sample size and its
      exploratory aims. RESULTS: High screeners used dramatic language (eg, patient
      stories) and mentioned risk of death, disability, or surgery from CRC in
      screening discussion role-plays more often than low screeners. High screeners
      frequently offered fecal occult blood testing, flexible sigmoidoscopy, and
      colonoscopy as equally acceptable screening options. High screeners more commonly
      described solutions for overcoming CRC screening barriers. CONCLUSIONS:
      Encouraging providers to use risk-specific messaging about the consequences of
      CRC, offering screening option choices, and promoting a problem-solving approach
      to surmount barriers are potential strategies for increasing CRC screening rates.

PMID- 23136317
TI  - Weight status and perception of colorectal cancer risk.
AB  - BACKGROUND: Obesity increases the risk of many cancers including colorectal
      cancer (CRC). METHODS: This is secondary data analysis of the 2010 National
      Health Interview Survey data. A total of 9360 obese and overweight participants,
      aged 50 to 80 years, were analyzed according to their perception of their
      personal cancer risk. RESULTS: Having a perception of increased risk for cancer
      was associated with higher CRC screening rates. However, when compared with their
      normal-weight counterparts, overweight and obese individuals did not perceive
      themselves as being at an increased risk for cancer in general or for CRC
      specifically. Subgroup analysis revealed one notable exception. Obese black women
      appeared to recognize themselves as being at higher risk for CRC. CONCLUSIONS:
      Most obese and overweight individuals fail to recognize their increased cancer
      risk. Individuals who perceive themselves as being at increased risk for cancer,
      especially CRC, are more likely to have undergone CRC screening. Unfortunately,
      obese and overweight individuals do not seem to recognize the increased cancer
      risk conferred by their body weight. Education is needed so that obese and
      overweight individuals are aware that their excess body weight is a risk factor
      for cancer.

PMID- 23136316
TI  - Physician recommendation and patient adherence for colorectal cancer screening.
AB  - BACKGROUND: Physician recommendation is one of the strongest, most consistent
      predictors of colorectal cancer (CRC) screening. Little is known regarding
      characteristics associated with patient adherence to physician recommendations in
      community and academic based primary care settings. METHODS: Data were analyzed
      from 975 patients, aged >=50 years, recruited from 25 primary care practices in
      New Jersey. Chi-square and generalized estimate equation analyses determined
      independent correlates of receipt of and adherence to physician recommendation
      for CRC. RESULTS: Patients reported high screening rates for CRC (59%). More than
      three fourths of patients reported either screening or having received a
      screening recommendation (82%). Men (P = .0425), nonsmokers (P = .0029), and
      patients who were highly educated (P = .0311) were more likely to receive a CRC
      screening recommendation. Patients more adhere to CRC screening recommendations
      were older adults (P < .0001), nonsmokers (P = .0005), those who were more highly
      educated (P = .0365), Hispanics (P = .0325), and those who were married (P <
      .0001). CONCLUSIONS: Community and academic primary care clinicians appropriately
      recommended screening to high-risk patients with familial risk factors. However,
      they less frequently recommended screening to others (ie, women and smokers) also
      likely to benefit. To further increase CRC screening, clinicians must
      systematically recommend screening to all patients who may benefit.

PMID- 23136318
TI  - Association of speculum lubrication with pain and Papanicolaou test accuracy.
AB  - PURPOSE: To determine the effects of lubrication of the vaginal speculum before
      insertion during a Papanicolaou test on perceived pain and quality of the
      cytology specimen. METHODS: Four hundred eligible women participating in cervical
      cancer screening and an early detection program were randomized with respect to
      lubricant gel use before speculum insertion. Perceived pain during speculum
      insertion and cytology results were assessed in study groups. RESULTS: The mean
      age of the patients was 45.7 years (range, 23-77 years). Pain score of the NO GEL
      group was significantly higher than that of the GEL group (2.3 and 1.6,
      respectively; P < .05). For premenopausal women, lubricant gel use significantly
      reduced the pain scores of the participants (P < .05). Cytological
      interpretations of the Papanicolaou test specimens were comparable among all
      groups. CONCLUSIONS: During the collection of Papanicolaou test specimens,
      lubrication of the vaginal speculum with a small amount of K-Y Jelly (a water
      soluble lubricant gel) decreases the pain associated with insertion of the
      vaginal speculum among postmenopausal women without obscuring the cytological
      interpretation of conventional or liquid-based cytology. In women of reproductive
      age, lubrication of the speculum with K-Y Jelly does not cause a meaningful
      effect with respect to perceived pain.

PMID- 23136319
TI  - Diuretic of choice in ABFM hypertension self-assessment module simulations.
AB  - BACKGROUND: Evidence suggests that chlorthalidone has therapeutic advantages over
      hydrochlorothiazide, perhaps because of a longer antihypertensive effect.
      Although guidelines such as the Seventh Report of the Joint National Committee on
      Prevention, Detection, Evaluation, and Treatment of High Blood Pressure treat
      diuretics as a class, some experts believe chlorthalidone is the diuretic of
      choice in hypertension management. We evaluated diplomates' use of chlorthalidone
      and hydrochlorothiazide as first-choice diuretics in virtual patient simulations
      of hypertension in the American Board of Family Medicine Maintenance of
      Certification for Family Physicians self-assessment modules. METHODS: We examined
      action logs for hypertension simulations completed between 2004 and 2011 and
      identified initial antihypertensive choices made by diplomates. We tabulated uses
      of any diuretic as initial treatment, distinguishing between chlorthalidone,
      hydrochlorothiazide, and other diuretic choices. We examined trends in the use of
      diuretics and chlorthalidone in simulations using linear models. RESULTS:
      Chlorthalidone use increased 0.7 percentage points per year (test for beta >0, P
      < .0013), from approximately 1.3% of simulation prescriptions in 2004 to about
      4.8% in 2010 and 2011, whereas hydrochlorothiazide prescriptions fell 2
      percentage points per year (P = .035), from nearly 57% to 47%. As a fraction of
      all diuretic use, chlorthalidone increased 1.4 percentage points per year (P =
      .0006), from 2% to 9%. CONCLUSIONS: Small but growing numbers of diplomates are
      heeding recommendations in the growing literature to start with chlorthalidone
      rather than hydrochlorothiazide, at least in the virtual patient environment.
      Observed choices in virtual patient management strongly imply that this is a
      valid topic for additional attention in the hypertension self-assessment module.

PMID- 23136320
TI  - Antibiotic prescription in febrile children: a cohort study during out-of-hours
      primary care.
AB  - BACKGROUND: Fever is common in children and often self-limiting, nevertheless
      antibiotics are frequently prescribed. We determined how often antibiotics were
      prescribed in children presenting with fever at a family physicians' out-of-hours
      service and established the children's signs and symptoms related to antibiotic
      prescriptions. PATIENTS: Children aged 3 months to 6 years with fever as the main
      reason for contact. RESULTS: Of the 443 included children, 322 children had a
      face-to-face contact at the out-of-hours service. Of these, 117 (36.3%) were
      prescribed antibiotics, that is, 26.5% of the total study population. Concerned
      parents (OR, 2.02; 95% CI, 1.06-3.58), ill appearance (3.26; 1.30-8.20), earache
      resulting in altered behavioral or sleeping patterns (2.59; 1.06-6.30), signs of
      throat infection (2.37; 1.35-4.15), and decreased urine production (2.00; 1.17
      3.41) were positively associated with antibiotic prescription. A negative
      association was found for age 3 to 6 months (0.17; 0.03-0.74) and temperature
      (0.52; 0.37-0.71). CONCLUSIONS: Antibiotics were prescribed in 1 out of 4 febrile
      children whose parents contacted the out-of-hours service. Items associated with
      antibiotic prescription provide insight into the family physicians' decision
      making process when assessing children with fever. These can be used as targets
      for strategies to diminish antibiotic prescription.

PMID- 23136321
TI  - The role of diabetes mellitus in the clinical presentation and prognosis of Bell
      palsy.
AB  - BACKGROUND: Bell palsy is considered to be an entrapment neuropathy resulting
      from inflammation, edema, and strangulation. Diabetes, hypertension, and
      hypercholesterolemia have all been related to microangiopathies. However, the
      relationship between the frequency, severity, and recovery course of Bell palsy
      in patients with these pathologies is a matter of controversy. METHODS: Fifty-six
      patients with Bell palsy were evaluated according to the House-Brackmann grading
      system a few days after the onset of the disease and 6 months later and
      correlated to their hypertension, hypercholesterolemia, and diabetes records.
      Diabetes was evaluated by the use of serum glycosylated hemoglobin (HbA1c).
      RESULTS: The 20 patients with abnormal HbA1c values were more frequently
      diagnosed with Bell palsy of grade V/VI (P = .008; odds ratio, 4.7; 95% CI, 1.4
      15.2). However, their House-Brackmann scores were not found to be worse at the 6
      month follow-up visit (P = .9). No correlations were found for hypertension and
      hypercholesterolemia. CONCLUSIONS: A relationship between the severity of Bell
      palsy and abnormal HbA1c values seems to be demonstrated. However, the prognosis
      of these patients does not seem to be worse because at the 6-month follow-up
      visit they present similar scores to nondiabetic patients.

PMID- 23136322
TI  - Plans to accommodate proposed maternity care training requirements: a national
      survey of family medicine directors of obstetrics curricula.
AB  - INTRODUCTION: Proposed changes to family medicine maternity care training
      requirements, including a 2-tiered basic and advanced curriculum, have raised
      questions about their perceived feasibility and impact. The goal of this study
      was to elicit family medicine obstetrics faculty plans to adopt changes in their
      maternity care training of family physicians. METHODS: We surveyed obstetrics
      curriculum directors at 423 family medicine residency programs, eliciting their
      plans to accommodate proposed maternity care training requirements. RESULTS: Two
      hundred nine programs participated (49.4% response rate). Of the curriculum
      adoption plans reported by directors, 41.7% anticipated using both curriculum
      models, 19.6% anticipated using the advanced model, 3.9% anticipated using the
      basic model, and 23.5% had no changes planned for their obstetrics curricula.
      CONCLUSIONS: Most programs plan structured changes, but a significant minority of
      programs plan no change to their curriculum based on proposed maternity care
      requirements.

PMID- 23136323
TI  - Association of "grit" and satisfaction in rural and nonrural doctors.
AB  - BACKGROUND: One potential psychological construct, grit, may help to explain the
      non-cognitive traits that account for both rural physician satisfaction and
      retention. We investigated (1) the psychological construct grit among rural and
      non-rural primary care/specialty care physicians, (2) satisfaction levels and
      (3), the relationship between the psychological construct grit and satisfaction
      across combinations of rural/non-rural and primary care/specialty care
      physicians. METHODS: We mailed a cross-sectional questionnaire to 2126 active
      members of the Idaho Medical Association and Idaho Academy of Family Physicians
      measuring their self-reported level of grit, satisfaction level and area of
      specialty. RESULTS: We received responses from 564 physicians (26.5%). Idaho
      physicians have relatively uniform levels of grit independent of specialty or
      practice location. Specialty care physicians reported significantly higher levels
      of ambition, regardless of practice location. Most physicians were satisfied with
      their practice (91.7%). Specialty care physicians reported a significantly higher
      difference in their levels of satisfaction with their practice compared to
      primary care physicians. CONCLUSIONS: Idaho primary care and specialty care
      physicians in both rural and non-rural settings reports themselves as individuals
      who work hard, persevere despite setbacks, and are ambitious. Furthermore, Idaho
      physicians are satisfied with their current practices.

PMID- 23136324
TI  - "Building through the grief": vicarious trauma in a group of inner-city family
      physicians.
AB  - BACKGROUND: Vicarious trauma is an understudied phenomenon among Canadian family
      physicians. OBJECTIVE: This phenomenological study set out to explore the
      experiences of a group of inner-city family physicians caring for women using
      illicit drugs. METHODS: Ten family physicians working in Toronto and Ottawa,
      Canada, participated in in-depth interviews. The data were analyzed using an
      iterative and interpretive process. RESULTS: The first major theme emerging from
      the data analysis was the emotional impact of the work. Participants shared the
      challenges, sorrows, and joys they experienced as they struggled to care for
      their patients. The sub-themes identified were as follows: tragedy and death,
      difficult behaviors, and isolation from mainstream medical community. The second
      major theme identified was coping strategies. Participants were open, thoughtful,
      and eloquent as they reflected on the three primary coping strategies reported:
      adaptation and evolution of practice style, teamwork, and modification of
      expectations. CONCLUSIONS: Participants, narratives of loss, grief, and
      compassion were consistent with vicarious trauma and therefore participants
      risked developing compassion fatigue--a specific form of burnout. These are new
      and important findings. Further research exploring vicarious trauma as a possible
      contributor to burnout among family physicians is warranted.

PMID- 23136325
TI  - The adult ADHD self-report scale for screening for adult attention deficit
      hyperactivity disorder (ADHD).
AB  - BACKGROUND: Adult attention deficit-hyperactivity disorder (ADHD) is
      underdiagnosed in the primary care setting despite 3% to 6% of adults having ADHD
      like symptoms. The Adult ADHD Self-Report Scale-V1.1 (ASRS-V1.1) is a validated,
      6-question screen for adult ADHD. Our purpose was to analyze this tool for
      evaluating patients in a busy primary care setting. METHODS: The ASRS-V1.1 was
      administered to patients in 8 busy primary care practices. All with a positive
      score and a random sample of those with a negative screening score were asked to
      complete the Conners' Adult ADHD Rating Scale Self Report-Short Version. Each was
      administered within the clinic setting during the same session. Sensitivity,
      specificity, and positive/negative predictive values were calculated. Data were
      evaluated for site-specific differences. RESULTS: It took an average of 54.3
      seconds (range, 22-252 seconds) to complete the ASRS-V1.1. There was an
      inconsistency-adjusted sensitivity of 1.0, a specificity of 0.71, a positive
      predictive value of 0.52, and a negative predictive value of 1.0. No site
      specific differences were found. CONCLUSIONS: Because of its ease of use, short
      time to administer, high sensitivity, and moderate specificity, the ASRS-V1.1 is
      an effective adult ADHD screening to guide further evaluations for ADHD.

PMID- 23136326
TI  - Does the "office nurse" level of training matter in the family medicine office?
AB  - BACKGROUND: The "office nurse" or clinical associate (registered nurse [RN],
      licensed practical nurse[LPN], or medical assistant [MA]) is a key member of the
      family medicine care team, but little is known about the influence of their level
      of training on team performance. METHODS: The performance of the clinical dyad
      (clinician and associate) was studied in relation to the level of training of the
      nurse. The dyad's performance was measured by the performance indicators of
      diabetes scores, patient satisfaction, and productivity. RESULTS: Dyads with a RN
      scored higher in meeting all 5 of the diabetes quality indicators (27.8%) than
      those with a LPN (19.3%) or an MA (14.7%). For patient satisfaction, the RN dyads
      also scored higher than the other dyad groups (positive responses: RN, 96.8%;
      LPN, 95.5%; MA, 94.6%). Productivity was the same in all groups. Better diabetes
      performance was seen in those practices with fewer competing demands: nonrural
      versus rural (22.2% vs 15.1%, respectively), and those not doing obstetrics
      versus those doing obstetrics (20.3% vs 15.1%, respectively), and for physicians
      versus associate providers (18.8% vs 15.1%, respectively). Higher patient
      satisfaction was observed in those dyads who were nonrural verus rural (96.6 vs
      94.1%), among those doing obstetrics (96.0% vs 94.9%), and in physicians verus
      associate providers (95.7% vs 93.2%). The number of years working with the same
      clinician was twice as high for RNs (6.63) and LPNs (6.57) than for MAs (3.29).
      CONCLUSIONS: A higher level of education of the clinical associate seems to
      confer skills that enhance the care team's management of chronic illness such as
      diabetes. This could potentially decrease the practice burden on other team
      members while facilitating the team's objectives in meeting quality indicators.

PMID- 23136327
TI  - Trends in physician house calls to Medicare beneficiaries.
AB  - OBJECTIVE: House calls (HCs) to older adults seemed to be headed for extinction
      in recent decades. HCs may be a tool to ensure access and reduce
      institutionalization of the elderly population. This study determines the number
      and distribution of HCs by physician specialty over time and analyzes
      associations of providing HCs with physician and area-level characteristics.
      METHODS: This study was a cross-sectional analysis of 3 complete Medicare Part B
      claims data for national state-representative samples of physicians in 2000,
      2003, and 2006. Multilevel logistic regression determined associations between
      physician and area-level characteristics and provision of HCs in 2006. RESULTS:
      Physicians made 478,088 HCs in 2000; 700,661 in 2003; and 995,294 in 2006. Over
      the same period, the proportion of physicians making HCs decreased from 7.22
      (standard error, +/-0.20) to 5.26 (+/-0.19). Physicians in the top decile of HC
      volume made an increasing number of HCs (median, 56 in 2000 and 86 in 2006). In
      2006, physicians who made HCs were more likely to be older, geriatricians, and
      osteopaths, be in solo practice, and reside in rural areas compared with those
      who did not make HCs. CONCLUSIONS: Between 2000 and 2006, the number of physician
      HCs to Medicare beneficiaries more than doubled, whereas the number of physicians
      making HCs declined.

PMID- 23136328
TI  - Defining the medical home: the Oregon experience.
AB  - OBJECTIVE: The patient-centered medical home (PCMH) is emerging as a key strategy
      to improve health outcomes, reduce total costs, and strengthen primary care, but
      a myriad of operational measures of the PCMH have emerged. In 2009, the state of
      Oregon convened a public, legislatively mandated committee charged with
      developing PCMH measures. We report on the process of, outcomes of, and lessons
      learned by this committee. METHODS: The Oregon PCMH advisory committee was
      appointed by the director of the Oregon Department of Human Services and held 7
      public meetings between October 2009 and February 2010. The committee engaged a
      diverse group of Oregon stakeholders, including a variety of practicing primary
      care physicians. RESULTS: The committee developed a PCMH measurement framework,
      including 6 core attributes, 15 standards, and 27 individual measures. Key
      successes of the committee's work were to describe PCMH core attributes and
      functions in patient-centered language and to achieve consensus among a diverse
      group of stakeholders. CONCLUSIONS: Oregon's PCMH advisory committee engaged
      local stakeholders in a process that resulted in a shared PCMH measurement
      framework and addressed stakeholders' concerns. The state of Oregon now has
      implemented a PCMH program using the framework developed by the PCMH advisory
      committee. The Oregon experience demonstrates that a brief public process can be
      successful in producing meaningful consensus on PCMH roles and functions and
      advancing PCMH policy.

PMID- 23136329
TI  - Night sweats: a systematic review of the literature.
AB  - BACKGROUND: Much of primary care involves helping patients manage symptoms.
      Nighttime sweating is a symptom linked to menopause, malignancies, autoimmune
      diseases, and infections. However, in primary care settings, night sweats are
      commonly reported by persons without these conditions. METHODS: We conducted a
      literature review, focusing on questions about definition, mechanisms,
      incidence/prevalence, measurement, clinical causes, evaluation, treatment, and
      prognosis. We limited our search to English language studies of adult humans
      published since 1966. Because studies of estrogen and androgen deficiency states
      had been reviewed by others, we excluded them. Search criteria were developed for
      each question. Publications meeting criteria were reviewed by the first 2 authors
      and consensus was reached through discussion. RESULTS: Prevalence estimates
      ranged from 10% among older primary care patients to 60% among women on an
      obstetrics inpatient unit. Life expectancy of primary care patients reporting
      night sweats did not appear to be reduced. Although many clinical causes have
      been suggested, most are not well supported. Algorithmic approaches to evaluation
      are not evidence-based. Alpha adrenergic blockers may reduce night sweats in
      patients taking serotonin reuptake inhibitors. Thalidomide and thioridazine may
      benefit some terminal cancer patients with night sweats. CONCLUSIONS: The
      symptom, night sweats, appears to be nonspecific. Many questions about causation,
      evaluation, and management remain unanswered.

PMID- 23136330
TI  - Match rates into family medicine among regional medical campus graduates, 2007
      2009.
AB  - BACKGROUND: Regional medical campuses (RMCs) are geographically separate from
      parent campuses, have administrative ties to deans' offices, and offer at least 4
      third-year clerkships. This study sought to describe the match rates into family
      medicine for graduates of RMCs and non-RMCs. METHODS: The authors obtained the
      2007 to 2009 match lists from schools participating in the Association of
      American Medical College's Group on Regional Medical Campuses. RMC match numbers
      for family medicine were subtracted from the total number of family medicine
      matched US seniors as published by the National Residency Match Program. The
      outcome of interest was the relative frequencies of RMC and non-RMC graduates
      matching into family medicine. RESULTS: Between 2007 and 2009, 261 graduates from
      29 RMCs accounted for 8% of all family medicine matches. During the study period,
      the match rate into family medicine for RMC graduates was 80% higher than that of
      non-RMC graduates (14.2% vs 7.9% for all 3 years). In 2009, only 3 of the RMCs
      had family medicine match rates lower than that of non-RMCs (7.5%). CONCLUSIONS:
      The RMC match rate into family medicine was nearly twice that of non-RMCs. RMCs
      may play a role in addressing physician workforce imbalances.

PMID- 23136331
TI  - Septic arthritis of the sternoclavicular joint.
AB  - Septic arthritis is a medical emergency that requires immediate action to prevent
      significant morbidity and mortality. The sternoclavicular joint may have a more
      insidious onset than septic arthritis at other sites. A high index of suspicion
      and judicious use of laboratory and radiologic evaluation can help solidify this
      diagnosis. The sternoclavicular joint is likely to become infected in the
      immunocompromised patient or the patient who uses intravenous drugs, but
      sternoclavicular joint arthritis in the former is uncommon. This case series
      describes the course of 2 immunocompetent patients who were treated
      conservatively for septic arthritis of the sternoclavicular joint.

PMID- 23136332
TI  - Eosinophilic gastroenteritis presenting with severe anemia and near syncope.
AB  - Eosinophilic gastrointestinal disorders or eosinophilic digestive disorders
      encompass a spectrum of rare gastrointestinal disorders that includes
      eosinophilic esophagitis, eosinophilic gastroenteritis, and eosinophilic colitis.
      Eosinophilic gastroenteritis is a rare inflammatory disease characterized by
      eosinophilic infiltration of the gastrointestinal tract. The clinical
      manifestations include anemia, dyspepsia, and diarrhea. Endoscopy with biopsy
      showing histologic evidence of eosinophilic infiltration is considered definitive
      for diagnosis. Corticosteroid therapy, food allergen testing, elimination diets,
      and elemental diets are considered effective treatments for eosinophilic
      gastroenteritis. The treatment and prognosis of eosinophilic gastroenteritis is
      determined by the severity of the clinical manifestations. We describe a 24-year
      old woman with eosinophilic gastroenteritis presenting as epigastric pain with a
      history of severe iron deficiency anemia, asthma, eczema, and allergic rhinitis,
      and we review the literature regarding presentation, diagnostic testing,
      pathophysiology, predisposing factors, and treatment recommendations.

PMID- 23136333
TI  - A "needling" problem: shoulder injury related to vaccine administration.
AB  - A 22-year-old woman with no significant medical history developed acute left
      shoulder pain and severe restrictions in range of motion after a seasonal
      influenza vaccine injection. Imaging by MRI, approximately 8 weeks after the
      injection, and by ultrasound, approximately 9.5 weeks after the injection
      demonstrated contusions on the humerus, injury of the supraspinatus, and effusion
      in the subacromial bursa. Her reaction was reported to the Vaccine Adverse Event
      Reporting System as a case of shoulder injury related to vaccine administration,
      likely due to injection of the influenza vaccine into the subacromial bursa. This
      case serves as a catalyst for discussion regarding vaccination technique and the
      potential to prevent complications arising from vaccine overpenetration.

PMID- 23136334
TI  - Health perceptions and levels of attachment: owners and pets exercising together.
AB  - BACKGROUND: Obesity is a parallel problem in canine and human populations. We
      describe health perceptions and levels of companion animal attachment in a cohort
      of dog owners. METHODS: As part of a larger trial examining the impact of
      veterinary counseling on activity levels of dog owners and their pets, owners
      presenting to a veterinary referral center were asked to self-report perceived
      levels of health and attachment to their dog (Lexington Attachment to Pets
      Scale). Owner body mass index and the body conditioning score of the companion
      dog were also recorded. RESULTS: Heavier pet owners reported a greater sense of
      attachment to their dogs. Heavier owners also reported lower perceived health and
      less social support. CONCLUSIONS: Increasing body mass index is associated with
      higher pet attachment, lower perceived health, and less social support. This
      information can impact wellness counseling for overweight pet owners and canine
      companions.

PMID- 23136335
TI  - The effect of lowering the prostate-specific antigen normal cutoff on referral
      rates to urology.
AB  - BACKGROUND: Routine prostate cancer screening is controversial, yet the use of
      prostate-specific antigen (PSA) for screening is likely to continue. Our hospital
      laboratory decreased the cutoff for normal PSA to 2.5 ng/mL on July 2, 2007,
      based on the National Comprehensive Screening Network recommendations. The
      purpose of this study was to determine if referral rates to urology increased
      after this change. METHODS: We queried our electronic health records to obtain
      the number of total screening PSA and abnormal PSA and subsequent referrals to
      urology in the 20-month periods before and after the change in PSA cutoff.
      RESULTS: There was no significant difference between the percentage of total
      screening PSA that resulted in a referral to urology after the change than before
      (7 of 199 [3.5%] vs 8 of 113 [7.1%]; P = .16). The percentage of abnormal PSA (as
      defined in the respective time periods) that were referred to urology actually
      decreased after the change (7 of 29 [24.1%] vs 6 of 10 [60.0%]; P = .04);
      however, when considering only PSA >4.0 ng/mL in each time period, there was no
      difference in percentage of referrals between the 2 periods. CONCLUSIONS:
      Contrary to expectations, lowering the cutoff for normal PSA did not increase
      referrals to urology.

PMID- 23136336
TI  - How I think: perspectives on process, people, politics, and presence.
AB  - The author, a seasoned midcareer family physician, summarizes his personal
      practice philosophy as it relates to encounters with patients. By focusing on 3
      aspects of care--process issues, people issues, and political issues--he explores
      the unique characteristics of his clinical decision-making process. He concludes
      by noting that it is through examination of the question "How do I think in the
      work I do?" that family physicians can best bring their signature presences to
      their encounters with patients and their families.

PMID- 23136337
TI  - Re: Consider muscle disease in children with elevated transaminase.

PMID- 23136340
TI  - Histaminergic modulation of nonspecific plasticity of the auditory system and
      differential gating.
AB  - In the auditory system of the big brown bat (Eptesicus fuscus), paired
      conditioned tonal (CS) and unconditioned leg stimuli (US) for auditory fear
      conditioning elicit tone-specific plasticity represented by best-frequency (BF)
      shifts that are augmented by acetylcholine, whereas unpaired CS and US for
      pseudoconditioning elicit a small BF shift and prominent nonspecific plasticity
      at the same time. The latter represents the nonspecific augmentations of auditory
      responses accompanied by the broadening of frequency tuning and decrease in
      threshold. It is unknown which neuromodulators are important in evoking the
      nonspecific plasticity. We found that histamine (HA) and an HA3 receptor (HA3R)
      agonist (alpha-methyl-HA) decreased, but an HA3R antagonist (thioperamide)
      increased, cortical auditory responses; that the HA3R agonist applied to the
      primary auditory cortex before pseudoconditioning abolished the nonspecific
      augmentation in the cortex without affecting the small cortical BF shift; and
      that antagonists of acetylcholine, norepinephrine, dopamine, and serotonin
      receptors did not abolish the nonspecific augmentation elicited by
      pseudoconditioning. The histaminergic system plays an important role in eliciting
      the arousal and defensive behavior, possibly through nonspecific augmentation.
      Thus HA modulates the nonspecific augmentation, whereas acetylcholine amplifies
      the BF shifts. These two neuromodulators may mediate differential gating of
      cortical plasticity.

PMID- 23136342
TI  - Transcallosal inhibition in patients with callosal infarction.
AB  - Recent studies in normal subjects suggested that callosal motor fibers pass
      through the posterior body of the corpus callosum (CC), but this has not been
      tested in patients with callosal infarction. The objective of this study is to
      define the pathways involved in transcallosal inhibition by examining patients
      with infarctions in different subregions of the CC. We hypothesized that patients
      with lesions in the posterior one-half of the CC would have greater reduction in
      transcallosal inhibition between the motor cortices. Twenty-six patients with
      callosal infarction and 14 healthy subjects were studied. The callosal lesions
      were localized on sagittal MRI and were attributed to one of five segments of the
      CC. Transcranial magnetic stimulation was used to assess ipsilateral silent
      period (iSP) and short- and long-latency interhemispheric inhibition (SIHI and
      LIHI, respectively) originating from both motor cortices. The results showed that
      the iSP areas and durations were markedly reduced bilaterally in patients with
      callosal infarction compared with normal subjects. Patients with callosal
      infarctions also had less IHI bidirectionally compared with normal subjects. iSP
      areas and durations were lower in patients with lesions than in patients without
      lesions in segment 3 (posterior midbody) of the CC. Lesion burden in the
      posterior one-half of the CC negatively correlated transcallosal inhibition
      measured with iSP and SIHI. Our study suggests that callosal infarction led to
      reduced transcallosal inhibition, as measured by iSP, SIHI, and LIHI. Fibers
      mediating transcallosal inhibition cross the CC mainly in the posterior one-half.

PMID- 23136341
TI  - Interaction of anesthetics with neurotransmitter release machinery proteins.
AB  - General anesthetics produce anesthesia by depressing central nervous system
      activity. Activation of inhibitory GABA(A) receptors plays a central role in the
      action of many clinically relevant general anesthetics. Even so, there is growing
      evidence that anesthetics can act at a presynaptic locus to inhibit
      neurotransmitter release. Our own data identified the neurotransmitter release
      machinery as a target for anesthetic action. In the present study, we sought to
      examine the site of anesthetic action more closely. Exocytosis was stimulated by
      directly elevating the intracellular Ca(2+) concentration at neurotransmitter
      release sites, thereby bypassing anesthetic effects on channels and receptors,
      allowing anesthetic effects on the neurotransmitter release machinery to be
      examined in isolation. Three different PC12 cell lines, which had the expression
      of different release machinery proteins stably suppressed by RNA interference,
      were used in these studies. Interestingly, there was still significant
      neurotransmitter release when these knockdown PC12 cells were stimulated. We have
      previously shown that etomidate, isoflurane, and propofol all inhibited the
      neurotransmitter release machinery in wild-type PC12 cells. In the present study,
      we show that knocking down synaptotagmin I completely prevented etomidate from
      inhibiting neurotransmitter release. Synaptotagmin I knockdown also diminished
      the inhibition produced by propofol and isoflurane, but the magnitude of the
      effect was not as large. Knockdown of SNAP-25 and SNAP-23 expression also changed
      the ability of these three anesthetics to inhibit neurotransmitter release. Our
      results suggest that general anesthetics inhibit the neurotransmitter release
      machinery by interacting with multiple SNARE and SNARE-associated proteins.

PMID- 23136343
TI  - A neuromechanical model for the neuronal basis of curve walking in the stick
      insect.
AB  - The coordination of the movement of single and multiple limbs is essential for
      the generation of locomotion. Movement about single joints and the resulting
      stepping patterns are usually generated by the activity of antagonistic muscle
      pairs. In the stick insect, the three major muscle pairs of a leg are the
      protractor and retractor coxae, the levator and depressor trochanteris, and the
      flexor and extensor tibiae. The protractor and retractor move the coxa, and
      thereby the leg, forward and backward. The levator and depressor move the femur
      up and down. The flexor flexes, and the extensor extends the tibia about the
      femur-tibia joint. The underlying neuronal mechanisms for a forward stepping
      middle leg have been thoroughly investigated in experimental and theoretical
      studies. However, the details of the neuronal and mechanical mechanisms driving a
      stepping single leg in situations other than forward walking remain largely
      unknown. Here, we present a neuromechanical model of the coupled three joint
      control system of the stick insect's middle leg. The model can generate forward,
      backward, or sideward stepping. Switching between them is achieved by changing
      only a few central signals controlling the neuromechanical model. In kinematic
      simulations, we are able to generate curve walking with two different mechanisms.
      In the first, the inner middle leg is switched from forward to sideward and in
      the second to backward stepping. Both are observed in the behaving animal, and in
      the model and animal alike, backward stepping of the inner middle leg produces
      tighter turns than sideward stepping.

PMID- 23136345
TI  - Perspective-taking in blindness: electrophysiological evidence of altered action
      representations.
AB  - It is well established that the mental simulation of actions involves visual
      and/or somatomotor representations of those imagined actions. To investigate
      whether the total absence of vision affects the brain activity associated with
      the retrieval of motor representations, we recorded the readiness potential (RP),
      a marker of motor preparation preceding the execution, as well as the motor
      imagery of the right middle-finger extension in the first-person (1P; imagining
      oneself performing the movement) and in the third-person (3P; imagining the
      experimenter performing the movement) modes in 19 sighted and 10 congenitally
      blind subjects. Our main result was found for the single RP slope values at the
      Cz channel (likely corresponding to the supplementary motor area). No difference
      in RP slope was found between 1P and 3P in the sighted group, suggesting that
      similar motor preparation networks are recruited to simulate our own and other
      people's actions in spite of explicit instructions to perform the task in 1P or
      3P. Conversely, reduced RP slopes in 3P compared with 1P found in the blind group
      indicated that they might have used an alternative, nonmotor strategy to perform
      the task in 3P. Moreover, movement imagery ability, assessed both by means of
      mental chronometry and a modified version of the Movement Imagery Questionnaire
      Revised, indicated that blind and sighted individuals had similar motor imagery
      performance. Taken together, these results suggest that complete visual loss
      early in life modifies the brain networks that associate with others' action
      representations.

PMID- 23136344
TI  - Preservation of VGLUT1 synapses on ventral calbindin-immunoreactive interneurons
      and normal locomotor function in a mouse model of spinal muscular atrophy.
AB  - Dysfunction in sensorimotor synapses is one of the earliest pathological changes
      observed in a mouse model [spinal muscular atrophy (SMA)Delta7] of spinal
      muscular atrophy. Here, we examined the density of proprioceptive and cholinergic
      synapses on calbindin-immunoreactive interneurons ventral to the lateral motor
      column. This population includes inhibitory Renshaw interneurons that are known
      to receive synaptic input from muscle spindle afferents and from motoneurons. At
      postnatal day (P)13, near the end stage of the disease, the somatic area of
      calbindin(+) neurons in the L1/L2 and L5/L6 segments was reduced in SMADelta7
      mice compared with controls. In addition, the number and density of terminals
      expressing the glutamate vesicular transporter (VGLUT1) and the vesicular
      acetylcholine transporter (VAChT) were increased on calbindin(+) cells in the L1
      L2 but not in the L5-L6 segments of SMADelta7 mice. In addition, the isolated
      spinal cord of SMA mice was able to generate locomotor-like activity at P4-P6 in
      the presence of a drug cocktail or in response to dorsal root stimulation. These
      results argue against a generalized loss of proprioceptive input to spinal
      circuits in SMA and suggest that the loss of proprioceptive synapses on
      motoneurons may be secondary to motoneuron pathology. The increased number of
      VGLUT1(+) and VAChT(+) synapses on calbindin(+) neurons in the L1/L2 segments may
      be the result of homeostatic mechanisms. Finally, we have shown that abnormal
      locomotor network function is unlikely to account for the motor deficits observed
      in SMA mice at P4-6.

PMID- 23136346
TI  - Failure of normal development of central drive to ankle dorsiflexors relates to
      gait deficits in children with cerebral palsy.
AB  - Neurophysiological markers of the central control of gait in children with
      cerebral palsy (CP) are used to assess developmental response to therapy. We
      measured the central common drive to a leg muscle in children with CP. We
      recorded electromyograms (EMGs) from the tibialis anterior (TA) muscle of 40
      children with hemiplegic CP and 42 typically developing age-matched controls
      during static dorsiflexion of the ankle and during the swing phase of treadmill
      walking. The common drive to TA motoneurons was identified through time- and
      frequency-domain cross-correlation methods. In control subjects, the common drive
      consists of frequencies between 1 and 60 Hz with peaks at beta (15-25 Hz) and
      gamma (30-45 Hz) frequencies known to be caused by activity within sensorimotor
      cortex networks: this drive to motoneurons strengthens during childhood. Similar
      to this drive in control subjects, this drive to the least affected TA in the CP
      children tended to strengthen with age, although compared with that in the
      control subjects, it was slightly weaker. For CP subjects of all ages, the most
      affected TA muscle common drive was markedly reduced compared with that of their
      least affected muscle as well as that of controls. These differences between the
      least and most affected TA muscles were unrelated to differences in the magnitude
      of EMG in the two muscles but positively correlated with ankle dorsiflexion
      velocity and joint angle during gait. Time- and frequency-domain analysis of
      ongoing EMG recruited during behaviorally relevant lower limb tasks provides a
      noninvasive and important measure of the central drive to motoneurons in subjects
      with CP.

PMID- 23136347
TI  - Motor learning and its sensory effects: time course of perceptual change and its
      presence with gradual introduction of load.
AB  - A complex interplay has been demonstrated between motor and sensory systems. We
      showed recently that motor learning leads to changes in the sensed position of
      the limb (Ostry DJ, Darainy M, Mattar AA, Wong J, Gribble PL. J Neurosci 30: 5384
      5393, 2010). Here, we document further the links between motor learning and
      changes in somatosensory perception. To study motor learning, we used a force
      field paradigm in which subjects learn to compensate for forces applied to the
      hand by a robotic device. We used a task in which subjects judge lateral
      displacements of the hand to study somatosensory perception. In a first
      experiment, we divided the motor learning task into incremental phases and
      tracked sensory perception throughout. We found that changes in perception
      occurred at a slower rate than changes in motor performance. A second experiment
      tested whether awareness of the motor learning process is necessary for
      perceptual change. In this experiment, subjects were exposed to a force field
      that grew gradually in strength. We found that the shift in sensory perception
      occurred even when awareness of motor learning was reduced. These experiments
      argue for a link between motor learning and changes in somatosensory perception,
      and they are consistent with the idea that motor learning drives sensory change.

PMID- 23136348
TI  - The dominant functional nicotinic receptor in progenitor cells in the rostral
      migratory stream is the alpha3beta4 subtype.
AB  - Addition of newly generated neurons into mature neural circuits in the adult CNS
      responds to changes in neurotransmitter levels and is tightly coupled to the
      activity of specific brain regions. This postnatal neurogenesis contributes to
      plasticity of the olfactory bulb and hippocampus and is thought to play a role in
      learning and memory, context and odor discrimination, as well as perceptual
      learning. While acetylcholine plays an important role in odor discrimination and
      perceptual learning, its role in adult neurogenesis in the olfactory bulb has not
      been elucidated. In this study, I have examined the functional expression of
      nAChRs in progenitor cells of the rostral migratory stream (RMS) in the adult
      olfactory bulb of mice. I show that most of these cells in the RMS exhibit large
      nAChR-mediated calcium transients upon application of acetylcholine (ACh). Unlike
      in the hippocampus, the predominant functional nAChRs on progenitor cells are of
      alpha3beta4 subtype. Interestingly, functional receptor expression is lost once
      progenitor cells mature, and are incorporated into the granule cell layer.
      Instead, nAChRs are now expressed on some presynaptic terminals and modulate
      glutamate release onto granule cells. My results imply that ACh is a part of the
      permissive niche and likely plays a role in development of progenitor cells.

PMID- 23136349
TI  - Novelty is not enough: laser-evoked potentials are determined by stimulus
      saliency, not absolute novelty.
AB  - Event-related potentials (ERPs) elicited by transient nociceptive stimuli in
      humans are largely sensitive to bottom-up novelty induced, for example, by
      changes in stimulus attributes (e.g., modality or spatial location) within a
      stream of repeated stimuli. Here we aimed 1) to test the contribution of a
      selective change of the intensity of a repeated stimulus in determining the
      magnitude of nociceptive ERPs, and 2) to dissect the effect of this change of
      intensity in terms of "novelty" and "saliency" (an increase of stimulus intensity
      is more salient than a decrease of stimulus intensity). Nociceptive ERPs were
      elicited by trains of three consecutive laser stimuli (S1-S2-S3) delivered to the
      hand dorsum at a constant 1-s interstimulus interval. Three, equally spaced
      intensities were used: low (L), medium (M), and high (H). While the intensities
      of S1 and S2 were always identical (L, M, or H), the intensity of S3 was either
      identical (e.g., HHH) or different (e.g., MMH) from the intensity of S1 and S2.
      Introducing a selective change in stimulus intensity elicited significantly
      larger N1 and N2 waves of the S3-ERP but only when the change consisted in an
      increase in stimulus intensity. This observation indicates that nociceptive ERPs
      do not simply reflect processes involved in the detection of novelty but,
      instead, are mainly determined by stimulus saliency.

PMID- 23136350
TI  - A cGMP-dependent protein kinase (PKG) controls synaptic transmission tolerance to
      acute oxidative stress at the Drosophila larval neuromuscular junction.
AB  - Increasing evidence demonstrates that modulating the cGMP-dependent protein
      kinase G (PKG) pathway produces an array of behavioral phenotypes in the fruit
      fly, Drosophila melanogaster. Altering PKG activity, either genetically via the
      foraging (for) gene or using pharmacology modifies tolerance to acute abiotic
      stresses such as hyperthermia and hypoxia. PKG signaling has been shown to
      modulate neuroprotection in many experimental paradigms of acute brain trauma and
      chronic neurodegenerative diseases. However, relatively little is known about how
      this stress-induced neuroprotective mechanism affects neural communication. In
      this study, we investigated the role PKG activity has on synaptic transmission at
      the Drosophila larval neuromuscular junction (NMJ) during acute oxidative stress
      and found that the application of 2.25 mM hydrogen peroxide (H(2)O(2)) disrupts
      synaptic function by rapidly increasing the rate of neuronal failure. Here, we
      report that reducing PKG activity through either natural genetic variation or an
      induced mutation of the for gene increases synaptic tolerance during acute
      oxidative conditions. Furthermore, pharmacological manipulations revealed that
      neurotransmission is significantly extended during acute H(2)O(2) exposure upon
      inhibition of the PKG pathway. Conversely, activation of this signaling cascade
      using either genetics or pharmacology significantly reduced the time until
      synaptic failure. Therefore, these findings suggest a potential role for PKG
      activity to regulate the tolerance of synaptic transmission during acute
      oxidative stress, where inhibition promotes functional protection while
      activation increases susceptibility to neurotransmission breakdown.

PMID- 23136351
TI  - New agents for the management of castration-resistant prostate cancer.
AB  - OBJECTIVE: To review the activity of 3 new agents approved for the management of
      advanced castration-resistant prostate cancer (CRPC): sipuleucel-T, cabazitaxel,
      and abiraterone acetate. DATA SOURCES: Literature was accessed through MEDLINE
      (1977-June 2012) and abstracts from the American Society of Clinical Oncology
      (2000-2012) using the terms castration-resistant and hormone-refractory prostate
      cancer, sipuleucel-T, cabazitaxel, abiraterone, Provenge, Jevtana, and Zytiga.
      Reference citations from publications identified were also reviewed. STUDY
      SELECTION AND DATA EXTRACTION: Articles identified from the data sources in
      English on human subjects were evaluated. DATA SYNTHESIS: Options for patients
      with CRPC have been limited, with little to offer those who failed or could not
      tolerate docetaxel-based therapy. Three new drugs, with very different mechanisms
      of action, have changed that and will undoubtedly change the treatment paradigm
      for these patients. Each agent has demonstrated an impact on patient survival.
      Sipuleucel-T, the first immunotherapy approved for treatment of CRPC, improved
      median overall survival by 4.1 months and reduced the risk of death by 22% in a
      placebo-controlled trial of asymptomatic patients. Sipuleucel-T can be
      administered prior to docetaxel-based therapy. Cabazitaxel, a taxane chemotherapy
      agent, improved median overall survival by 2.4 months and reduced the risk of
      death by 30% in a Phase 3 trial of patients whose cancer progressed during or
      after docetaxel-based therapy. Abiraterone acetate, a hormonal therapy, improved
      median overall survival by 3.9 months and reduced the risk of death by 35% in
      patients with relapse during or after docetaxel-based therapy. CONCLUSIONS: The
      advent of new agents for the management of advanced CRPC has increased the
      choices for patients whose options were limited. Additional experience will
      determine the optimal sequencing of these agents, their roles in combination
      therapy, and their activity in patients with earlier disease.

PMID- 23136352
TI  - Pancreatitis: a potential complication of liraglutide?
AB  - OBJECTIVE: To review the evidence surrounding a potential association between
      liraglutide and pancreatitis. DATA SOURCES: A literature search was conducted in
      MEDLINE (1948-July 12, 2012) and EMBASE (1974-week 27, 2012) using the search
      terms pancreatitis, liraglutide, and glucagon-like peptide 1/adverse effects.
      Reference citations from identified publications were reviewed. The manufacturer
      was contacted and regulatory documents from the Food and Drug Administration
      website were reviewed for unpublished data related to cases of pancreatitis
      associated with liraglutide use. STUDY SELECTION AND DATA EXTRACTION: All
      identified sources that were published in English were considered for inclusion.
      DATA SYNTHESIS: Eleven cases of pancreatitis have been reported in patients
      taking liraglutide. Seven were from the LEAD (Liraglutide Effect and Action in
      Diabetes) studies, 1 was reported in the extension of a clinical trial, and 1 was
      in an unpublished obesity trial. Two were published postmarketing case reports.
      Nine of the cases reported were diagnosed as acute pancreatitis, while 2 were
      classified as chronic pancreatitis. The mean age of the patients was 57.5 years
      and mean body mass index was 33.92 kg/m(2). Six of the 11 cases occurred in male
      patients. Nine of the patients were white and 1 was African American. In 7 of the
      cases, onset occurred at liraglutide doses at or above 1.8 mg daily. Common
      comorbidities included history of pancreatitis, cholelithiasis, and diabetes. One
      case was fatal. CONCLUSIONS: Pancreatitis is a potential complication with
      liraglutide therapy. Liraglutide should be used cautiously in patients at risk of
      pancreatitis (eg, alcohol abuse, history of pancreatitis, cholelithiasis).

PMID- 23136353
TI  - Efficacy and safety of dipeptidyl peptidase-4 inhibitors in type 2 diabetes: meta
      analysis.
AB  - BACKGROUND: An up-to-date assessment of dipeptidyl peptidase-4 (DPP-4) inhibitors
      is needed to include newly available data. OBJECTIVE: To assess the efficacy and
      safety of DPP-4 inhibitors, including sitagliptin, saxagliptin, vildagliptin, and
      linagliptin, in type 2 diabetes. METHODS: We conducted a search of MEDLINE for
      randomized controlled trials (RCTs) of DPP-4 inhibitors in type 2 diabetes
      through November 2011, using the key terms sitagliptin, saxagliptin,
      vildagliptin, and linagliptin. We also searched for completed, but unpublished,
      trials at relevant web sites. RCTs were selected for meta-analysis if they (1)
      compared DPP-4 inhibitors with placebo or an antihyperglycemic agent; (2) had
      study duration of 12 or more weeks; (3) had 1 or more baseline and posttreatment
      efficacy and/or safety outcome; and (4) were published in English. RESULTS: In 62
      evaluated articles, DPP-4 inhibitors lowered hemoglobin A(1c) (A1C) significantly
      more than placebo (weighted mean difference [WMD] -0.76%; 95% CI -0.83 to -0.68);
      however, heterogeneity was substantial (I(2) = 82%). Exclusion of Japanese trials
      (n = 7) resulted in a reduction of heterogeneity (I(2) = 59%). In the non
      Japanese RCTs (n = 55), DPP-4 inhibitors were associated with a reduction in A1C
      (WMD -0.65%; 95% CI -0.71 to -0.60) but higher risk of hypoglycemia (odds ratio
      [OR] 1.30; 95% CI 1.00 to 1.68) compared to placebo. The 7 Japanese-specific RCTs
      showed a greater reduction in A1C (WMD -1.67%; 95% CI -1.89 to -1.44) and a
      nonsignificant increase in risk of hypoglycemia (OR 1.41; 95% CI 0.51 to 3.88)
      with DPP-4 inhibitors versus placebo. When comparing DPP-4 inhibitors to active
      comparators, the I(2) was still high after deleting Japanese studies. In these 17
      active comparator trials, there was no significant difference in A1C reduction
      (WMD 0.04%; 95% CI -0.09 to 0.16) or risk of hypoglycemia (OR 0.60; 95% CI 0.22
      to 1.61) for DPP-4 inhibitors compared to other antihyperglycemics. There were
      similar odds of any or serious adverse events with DPP-4 inhibitors compared to
      placebo, but a decreased risk compared to other antihyperglycemics. CONCLUSIONS:
      DPP-4 inhibitors were associated with a reduction in A1C with comparable safety
      profiles compared to placebo, but no significant difference in A1C compared to
      other hyperglycemics. Differences in efficacy and safety were observed between
      Japanese and non-Japanese patients.

PMID- 23136354
TI  - Stopping trials early for benefit--not so fast!
AB  - On October 25, 2011, Eli Lilly and Company announced the voluntary withdrawal of
      Xigris (drotrecogin alfa [activated]) following the negative results of its most
      recent clinical trial, the PROWESS-SHOCK study. The purpose of this commentary is
      to briefly review the history of drotrecogin alfa, discuss issues surrounding
      early cessation of clinical trials for benefit, and highlight the scientific and
      ethical dilemmas faced when deciding whether or not to stop a trial early for
      benefit. This review should serve as an introduction to the topic of stopping
      trials early for benefit.

PMID- 23136355
TI  - Thiazide diuretics as chronic antihypertensive therapy in patients with severe
      renal disease--is there a role in the absence of diuresis?
AB  - OBJECTIVE: To determine whether thiazides have a chronic antihypertensive effect,
      in the absence of diuresis, in patients with severe renal disease (creatinine
      clearance <30 mL/min) or in those receiving dialysis. DATA SOURCES: A search was
      performed in PubMed, CENTRAL, and International Pharmaceutical Abstracts, using
      MeSH terms and/or key words. MeSH terms included kidney failure, chronic and
      exploded terms hydrochlorothiazide, renal dialysis, and thiazides. Key words
      included thiazide*, hydrochlorothiazide, chlorothiazide, chlorthalidone,
      indapamide, metolazone, methyclothiazide, bendroflumethiazide, hemodialysis,
      dialysis, kidney failure, renal failure, renal insufficiency, hypertension,
      vasodilation, vascular, and diuretics. STUDY SELECTION AND DATA EXTRACTION: All
      relevant English-language publications were evaluated. Studies evaluating the
      efficacy of thiazides in renal insufficiency or dialysis were limited to those
      that included blood pressure measurements. Studies were included only if
      treatment duration was at least 4 weeks to evaluate chronic antihypertensive
      effects. DATA SYNTHESIS: Thiazide diuretics are associated with a chronic
      reduction in peripheral vascular resistance secondary to a purported vasodilatory
      effect. However, few clinical studies have evaluated the chronic antihypertensive
      efficacy of thiazide and thiazide-like diuretics in patients with severe renal
      disease or those on dialysis. Agents studied include hydrochlorothiazide,
      chlorothiazide, indapamide, and metolazone, with results varying by drug and
      patient population. Hydrochlorothiazide 25-200 mg daily, chlorothiazide 500 mg
      twice daily, and indapamide 2.5 mg daily provided long-term blood pressure
      reduction in patients with severe renal disease who were not on dialysis. In
      studies involving patients on dialysis, hydrochlorothiazide 50 mg daily and
      metolazone 5 mg daily did not affect blood pressure; however, 1 study suggested
      that indapamide 2.5 mg daily may confer an antihypertensive effect. All studies
      were small (<=12 subjects) and had methodological limitations. CONCLUSIONS:
      Thiazide diuretics may decrease peripheral vascular resistance independent of
      natriuresis. However, because current clinical data are inconclusive as to the
      efficacy of these agents at chronically lowering blood pressure in patients with
      severe renal disease or in those on dialysis, thiazide diuretics cannot be
      routinely recommended for this indication.

PMID- 23136356
TI  - Antimicrobial stewardship pharmacist interventions for coagulase-negative
      staphylococci positive blood cultures using rapid polymerase chain reaction.
AB  - BACKGROUND: No studies exist regarding the value of pharmacist interventions
      using rapid identification of coagulase-negative staphylococci (CoNS) by rapid
      polymerase chain reaction (rPCR) from blood cultures. OBJECTIVE: To evaluate the
      impact of interventions by infectious diseases pharmacists (ID PharmDs) on blood
      cultures positive for CoNS using rPCR and assess the duration of
      antistaphylococcal antibiotic therapy, hospital length of stay (LOS), and related
      costs. METHODS: A quasi-experimental, pre- and postintervention study of patients
      with positive blood cultures for CoNS, identified using rPCR, was conducted.
      Patients were included if there was a blood culture for CoNS from January 1,
      2011, to March 31, 2011 (preintervention), or October 1, 2011, to January 18,
      2012 (postintervention). Exclusion criteria included age younger than 18 years or
      89 years or older, neutropenia, incomplete records, and duplicate or mixed blood
      cultures. The setting was a 1200-bed academic medical center. The ID PharmD
      intervened on blood cultures identified in the postintervention group as CoNS
      after notification from the microbiology laboratory. The pre- and
      postintervention groups were compared to analyze the effect of the intervention.
      The primary outcome was time to discontinuation of antistaphylococcal antibiotics
      by the pharmacist intervention in patients with a positive blood culture for CoNS
      that was determined to be a contaminant. RESULTS: We analyzed 53 patients (31
      preintervention, 22 postintervention) with CoNS blood culture contaminants. In
      the postintervention group, antistaphylococcal antibiotics were discontinued 32.0
      hours sooner from time of rPCR result (median 57.7 vs 25.7 hours; p = 0.005),
      total antibiotic exposure decreased 43.5 hours (97.6 vs 54.1 hours; p = 0.011),
      infection-related LOS decreased 4.5 days (10 vs 5.5 days; p = 0.018), and
      infection-related costs decreased $8338 ($28,973 vs $20,635; p = 0.144). The
      pharmacist initiated vancomycin in 7 (21.9%) patients with CoNS bloodstream
      infections. CONCLUSIONS: Timely interventions by ID PharmDs using rPCR are
      required to impact the outcomes of patients with positive blood cultures for
      CoNS.

PMID- 23136357
TI  - Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate single tablet
      for HIV-1 infection treatment.
AB  - OBJECTIVE: To review the clinical trials, pharmacologic characteristics, safety,
      and efficacy of the elvitegravir/cobicistat/emtricitabine/tenofovir single tablet
      formulation (Stribild). DATA SOURCES: Literature searches were performed in
      MEDLINE (1948-September 2012) and PubMed (1966-September 2012) using the search
      terms GS-9137, elvitegravir, GS 9350, cobicistat, quad pill, Stribild, and
      integrase inhibitors. Abstracts from HIV/AIDS conferences were reviewed. STUDY
      SELECTION AND DATA EXTRACTION: Phase 3 studies evaluating the safety and efficacy
      of Stribild were preferentially evaluated, as well as relevant references from
      the published studies. DATA SYNTHESIS: Stribild contains complete antiretroviral
      therapy for HIV-1 infection in a single tablet. It is the first once-daily
      therapy option available with an integrase inhibitor and a novel pharmacokinetic
      boosting agent. Stribild has shown noninferiority in viral load suppression at 48
      weeks when compared with dual nucleoside/nucleotide reverse transcriptase
      inhibitor and either a ritonavir-boosted protease inhibitor or nonnucleoside
      reverse transcriptase inhibitor regimen. Stribild was well tolerated, but some
      patients experienced increases in serum creatinine early in treatment that
      stabilized over time. CONCLUSIONS: Stribild is the first single-tablet regimen
      for HIV-1 infection treatment containing an integrase inhibitor. It is expected
      to have a prominent place in the formularies of health plans providing care for
      individuals with HIV-1 infection.

PMID- 23136359
TI  - Colon cancer recurrence: insights from the interface between epidemiology,
      laboratory science, and clinical medicine.

PMID- 23136358
TI  - Dietary glycemic load and cancer recurrence and survival in patients with stage
      III colon cancer: findings from CALGB 89803.
AB  - BACKGROUND: The influence of glycemic load and related measures on survival among
      colon cancer patients remains largely unknown. METHODS: We conducted a
      prospective, observational study of 1011 stage III colon cancer patients
      reporting dietary intake during and 6 months after participation in an adjuvant
      chemotherapy trial. We examined the influence of glycemic load, glycemic index,
      fructose, and carbohydrate intakes on cancer recurrence and mortality using Cox
      proportional hazards regression; all tests of statistical significance were two
      sided. RESULTS: Stage III colon cancer patients in the highest quintile of
      dietary glycemic load experienced an adjusted hazard ratio (HR) for disease-free
      survival of 1.79 (95% confidence interval [CI] = 1.29 to 2.48), compared with
      those in the lowest quintile (P (trend) across quintiles <.001). Increased
      glycemic load was associated with similar detriments in recurrence-free (P
      (trend) across quintiles <.001) and overall survival (P (trend) across quintiles
      <.001). These associations differed statistically significant by body mass index
      (BMI) (P (interaction) =.01). Whereas glycemic load was not associated with
      disease-free survival in patients with BMI < 25kg/m(2), higher glycemic load was
      statistically significant associated with worse disease-free survival among
      overweight or obese participants (BMI >= 25kg/m(2); HR = 2.26; 95% CI = 1.53 to
      3.32; P (trend) across quintiles <.001). Increasing total carbohydrate intake was
      similarly associated with inferior disease-free, recurrence-free, and overall
      survival (P (trend) across quintiles <.001). CONCLUSION: Higher dietary glycemic
      load and total carbohydrate intake were statistically significant associated with
      an increased risk of recurrence and mortality in stage III colon cancer patients.
      These findings support the role of energy balance factors in colon cancer
      progression and may offer potential opportunities to improve patient survival.

PMID- 23136360
TI  - Molecular evolution of lineage 2 West Nile virus.
AB  - Since the 1990s West Nile virus (WNV) has become an increasingly important public
      health problem and the cause of outbreaks of neurological disease. Genetic
      analyses have identified multiple lineages with many studies focusing on lineage
      1 due to its emergence in New York in 1999 and its neuroinvasive phenotype. Until
      recently, viruses in lineage 2 were not thought to be of public health importance
      due to few outbreaks of disease being associated with viruses in this lineage.
      However, recent epidemics of lineage 2 in Europe (Greece and Italy) and Russia
      have shown the increasing importance of this lineage. There are very few genetic
      studies examining isolates belonging to lineage 2. We have sequenced the full
      length genomes of four older lineage 2 WNV isolates, compared them to 12
      previously published genomic sequences and examined the evolution of this
      lineage. Our studies show that this lineage has evolved over the past 300-400
      years and appears to correlate with a change from mouse attenuated to virulent
      phenotype based on previous studies by our group. This evolution mirrors that
      which is seen in lineage 1 isolates, which have also evolved to a virulent
      phenotype over the same period of time.

PMID- 23136361
TI  - Dugbe virus ovarian tumour domain interferes with ubiquitin/ISG15-regulated
      innate immune cell signalling.
AB  - The ovarian tumour (OTU) domain of the nairovirus L protein has been shown to
      remove ubiquitin and interferon-stimulated gene 15 protein (ISG15) from host cell
      proteins, which is expected to have multiple effects on cell signalling pathways.
      We have confirmed that the OTU domain from the L protein of the apathogenic
      nairovirus Dugbe virus has deubiquitinating and deISGylating activity and shown
      that, when expressed in cells, it is highly effective at blocking the TNF
      alpha/NF-kappaB and interferon/JAK/STAT signalling pathways even at low doses.
      Point mutations of the catalytic site of the OTU [C40A, H151A and a double
      mutant] both abolished the ability of the OTU domain to deubiquitinate and
      deISGylate proteins and greatly reduced its effect on cell signalling pathways,
      confirming that it is this enzymic activity that is responsible for blocking the
      two signalling pathways. Expression of the inactive mutants at high levels could
      still block signalling, suggesting that the viral OTU can still bind to its
      substrate even when mutated at its catalytic site. The nairovirus L protein is a
      very large protein that is normally confined to the cytoplasm, where the virus
      replicates. When the OTU domain was prevented from entering the nucleus by
      expressing it as part of the N-terminal 205 kDa of the viral L protein, it
      continued to block type I interferon signalling, but no longer blocked the TNF
      alpha-induced activation of NF-kappaB.

PMID- 23136362
TI  - Toll-like receptor 7 suppresses virus replication in neurons but does not affect
      viral pathogenesis in a mouse model of Langat virus infection.
AB  - Toll-like receptor 7 (TLR7) recognizes guanidine-rich viral ssRNA and is an
      important mediator of peripheral immune responses to several ssRNA viruses.
      However, the role that TLR7 plays in regulating the innate immune response to
      ssRNA virus infections in specific organs such as the central nervous system
      (CNS) is not as clear. This study examined the influence of TLR7 on the
      neurovirulence of Langat virus (LGTV), a ssRNA tick-borne flavivirus. TLR7
      deficiency did not substantially alter the onset or incidence of LGTV-induced
      clinical disease; however, it did significantly affect virus levels in the CNS
      with a log(10) increase in virus titres in brain tissue from TLR7-deficient mice.
      This difference in virus load was also observed following intracranial
      inoculation, indicating a direct effect of TLR7 deficiency on regulating virus
      replication in the brain. LGTV-induced type I interferon responses in the CNS
      were not dependent on TLR7, being higher in TLR7-deficient mice compared with
      wild-type controls. In contrast, induction of pro-inflammatory cytokines
      including tumour necrosis factor, CCL3, CCL4 and CXCL13 were dependent on TLR7.
      Thus, although TLR7 is not essential in controlling LGTV pathogenesis, it is
      important in controlling virus infection in neurons in the CNS, possibly by
      regulating neuroinflammatory responses.

PMID- 23136363
TI  - Protease-sensitive prion species in neoplastic spleens of prion-infected mice
      with uncoupling of PrP(Sc) and prion infectivity.
AB  - Prion diseases are fatal neurodegenerative disorders. An important step in
      disease pathophysiology is the conversion of cellular prion protein (PrP(C)) to
      disease-associated misfolded conformers (PrP(Sc)). These misfolded PrP variants
      are a common component of prion infectivity and are detectable in diseased brain
      and lymphoreticular organs such as spleen. In the latter, PrP(Sc) is thought to
      replicate mainly in follicular dendritic cells within spleen follicles. Although
      the presence of PrP(Sc) is a hallmark for prion disease and serves as a main
      diagnostic criterion, in certain instances the amount of PrP(Sc) does not
      correlate well with neurotoxicity or prion infectivity. Therefore, it has been
      proposed that prions might be a mixture of different conformers and aggregates
      with differing properties. This study investigated the impact of disruption of
      spleen architecture by neoplasia on the abundance of different PrP species in
      spleens of prion-infected mice. Although follicular integrity was completely
      disturbed, titres of prion infectivity in neoplastic spleens were not
      significantly altered, yet no protease-resistant PrP(Sc) was detectable. Instead,
      unique protease-sensitive prion species could be detected in neoplastic spleens.
      These results indicate the dissociation of PrP(Sc) and prion infectivity and
      showed the presence of non-PrP(Sc) PrP species in spleen with divergent
      biochemical properties that become apparent after tissue architecture disruption.

PMID- 23136364
TI  - Characterization of white spot syndrome virus immediate-early gene promoters.
AB  - Twenty-one immediate-early (IE) genes of white spot syndrome virus (WSSV) have
      been identified so far. However, the transcriptional regulation of WSSV IE genes
      remains largely unknown. In this report, the 5' flanking regions of 18 WSSV IE
      genes were cloned and eight functional promoter regions were identified. WSSV IE
      gene promoters normally contained a TATA box approximately 30 bp upstream of the
      transcriptional initiation site. Also, the cyclic AMP response element (CRE;
      TGACGTCA) was frequently found within the WSSV IE promoter regions. Mutations of
      the CREs of WSSV IE promoters P403 and P465 reduced their activity significantly,
      suggesting that these elements have a role in WSSV IE gene transcription. Our
      findings provide a more global view of WSSV IE gene promoters and will facilitate
      the in-depth investigation of viral gene transcriptional regulation.

PMID- 23136365
TI  - Gag sequence variation in a human immunodeficiency virus type 1 transmission
      cluster influences viral replication fitness.
AB  - Three men from a proven homosexual human immunodeficiency virus type 1 (HIV-1)
      transmission cluster showed large variation in their clinical course of
      infection. To evaluate the effect of evolution of the same viral variant in these
      three patients, we analysed sequence variation in the capsid protein and
      determined the impact of the observed variation on viral replication fitness in
      vitro. Viral gag sequences from all three patients contained a mutation at
      position 242, T242N or T242S, which have been associated with lower virus
      replication in vitro. Interestingly, HIV-1 variants from patients with a
      progressive clinical course of infection developed compensatory mutations within
      the capsid that restored viral fitness, instead of reversion of the T242S
      mutation. In HIV-1 variants from patient 1, an HLA-B57(+) elite controller, no
      compensatory mutations emerged during follow-up.

PMID- 23136366
TI  - Systemic transport of Alfalfa mosaic virus can be mediated by the movement
      proteins of several viruses assigned to five genera of the 30K family.
AB  - We previously showed that the movement protein (MP) gene of Alfalfa mosaic virus
      (AMV) is functionally exchangeable for the cell-to-cell transport of the
      corresponding genes of Tobacco mosaic virus (TMV), Brome mosaic virus, Prunus
      necrotic ringspot virus, Cucumber mosaic virus and Cowpea mosaic virus. We have
      analysed the capacity of the heterologous MPs to systemically transport the
      corresponding chimeric AMV genome. All MPs were competent in systemic transport
      but required the fusion at their C terminus of the coat protein-interacting C
      terminal 44 aa (A44) of the AMV MP. Except for the TMV MP, the presence of the
      hybrid virus in upper leaves correlated with the capacity to move locally. These
      results suggest that all the MPs assigned to the 30K superfamily should be
      exchangeable not only for local virus movement but also for systemic transport
      when the A44 fragment is present.

PMID- 23136367
TI  - Synonymous site variation due to recombination explains higher genetic
      variability in begomovirus populations infecting non-cultivated hosts.
AB  - Begomoviruses are ssDNA plant viruses that cause serious epidemics in
      economically important crops worldwide. Non-cultivated plants also harbour many
      begomoviruses, and it is believed that these hosts may act as reservoirs and as
      mixing vessels where recombination may occur. Begomoviruses are notoriously
      recombination-prone, and also display nucleotide substitution rates equivalent to
      those of RNA viruses. In Brazil, several indigenous begomoviruses have been
      described infecting tomatoes following the introduction of a novel biotype of the
      whitefly vector in the mid-1990s. More recently, a number of viruses from non
      cultivated hosts have also been described. Previous work has suggested that
      viruses infecting non-cultivated hosts have a higher degree of genetic
      variability compared with crop-infecting viruses. We intensively sampled
      cultivated and non-cultivated plants in similarly sized geographical areas known
      to harbour either the weed-infecting Macroptilium yellow spot virus (MaYSV) or
      the crop-infecting Tomato severe rugose virus (ToSRV), and compared the molecular
      evolution and population genetics of these two distantly related begomoviruses.
      The results reinforce the assertion that infection of non-cultivated plant
      species leads to higher levels of standing genetic variability, and indicate that
      recombination, not adaptive selection, explains the higher begomovirus
      variability in non-cultivated hosts.

PMID- 23136368
TI  - Identification of human papillomavirus type 156, the prototype of a new human
      gammapapillomavirus species, by a generic and highly sensitive PCR strategy for
      long DNA fragments.
AB  - This study developed a hanging-droplet long PCR, a generic and highly sensitive
      strategy to facilitate the identification of new human papillomavirus (HPV)
      genomes. This novel procedure used for the first time the hanging-droplet PCR
      technique for the amplification of long DNA fragments with generic primers
      targeting the L1 and E1 regions. It was first applied to the amplification of
      types belonging to the highly divergent genus Gammapapillovirus (gamma-PV). The
      hanging-droplet long PCR was 100-fold more sensitive than a simple long PCR
      procedure, detecting as few as ten copies of HPV-4. Nineteen skin samples,
      potentially containing putative HPV types from the gamma-PV genus, were also
      screened. The method identified four gamma-PV genomic halves from new and
      previously described putative types, and made the full characterization of HPV
      156 possible. This novel virus meets the criteria for a new species within the
      gamma-PV genus, with nucleotide identities in the L1 ORF ranging from 58.3 to
      67.3 % compared with representative types of the current gamma-PV species. HPV
      156 showed the highest identity to HPV-60 (67.3 %) from species gamma-4, and was
      consistently closely related to it in both late- and early-gene-derived
      phylogenies. In conclusion, this report provides a versatile and highly sensitive
      approach that allowed identification of the prototype of a new species within the
      gamma-PV genus. Its application with primers targeting the different genera in
      which both human and non-human PVs are distributed may facilitate
      characterization of the missing members of the family Papillomaviridae.

PMID- 23136369
TI  - Heterogeneity of West Nile virus genotype 1a in Italy, 2011.
AB  - West Nile virus (WNV) is currently circulating in several European countries and,
      over recent decades, concomitantly with enhanced surveillance studies and
      improved diagnostic capabilities, an increase in the geographical distribution
      and in the number of cases in Europe has been documented. In Italy in 2011, 14
      human cases of WNV neuroinvasive infections due to lineage 1 strains were
      registered in several Italian regions. Here we report WNV partial sequences
      obtained from serum samples of two patients living in different regions of Italy
      (Veneto and Sardinia). Phylogenetic analysis, performed on a fragment (566 nt) of
      the envelope gene, showed that WNV strains circulating in Italy in 2011 belong to
      lineage 1a, but are different from lineage 1a strains isolated in 2008-2009.The
      data reported here are consistent with the hypothesis of multiple recent
      introductions of WNV lineage 1a strains into Italy.

PMID- 23136370
TI  - Obesity is inversely associated with natural amenities and recreation facilities
      per capita.
AB  - BACKGROUND: Little is known about the associations between natural amenities,
      recreation facility density, and obesity, at a national level. Therefore, the
      purpose of this paper was to examine associations between county-level natural
      amenities, density of recreation facilities, and obesity prevalence among United
      States counties. METHODS: Data were obtained from a compilation of sources within
      the United States Department of Agriculture Economic Research Service Food
      Environment Atlas. Independent variables of interest were the natural amenities
      scale and recreation facilities per capita. The dependent variable was county
      level obesity prevalence. Potential covariates included a measure of county-level
      percent Black residents, percent Hispanic residents, median age, and median
      household income. All models were stratified by population loss, persistent
      poverty, and metro status. Multilevel linear regression models were used to
      examine the association between obesity and natural amenities and recreation
      facilities, with "state" as a random effects second level variable. RESULTS:
      There were statistically significant negative associations between percent
      obesity and 1) natural amenities and 2) recreation facilities per capita.
      CONCLUSIONS: Future research should examine environmental and policy changes to
      increase recreation facilities and enhance accessible natural amenities to
      decrease obesity rates.

PMID- 23136371
TI  - Development and validation of energy expenditure prediction models based on GT3X
      accelerometer data in 5- to 9-year-old children.
AB  - BACKGROUND: Accelerometry has been established as an objective method that can be
      used to assess physical activity behavior in large groups. The purpose of the
      current study was to provide a validated equation to translate accelerometer
      counts of the triaxial GT3X into energy expenditure in young children. METHODS:
      Thirty-two children aged 5-9 years performed locomotor and play activities that
      are typical for their age group. Children wore a GT3X accelerometer and their
      energy expenditure was measured with indirect calorimetry. Twenty-one children
      were randomly selected to serve as development group. A cubic 2-regression model
      involving separate equations for locomotor and play activities was developed on
      the basis of model fit. It was then validated using data of the remaining
      children and compared with a linear 2-regression model and a linear 1-regression
      model. RESULTS: All 3 regression models produced strong correlations between
      predicted and measured MET values. Agreement was acceptable for the cubic model
      and good for both linear regression approaches. CONCLUSIONS: The current linear 1
      regression model provides valid estimates of energy expenditure for ActiGraph
      GT3X data for 5- to 9-year-old children and shows equal or better predictive
      validity than a cubic or a linear 2-regression model.

PMID- 23136372
TI  - Crystal structure of an indole-3-acetic acid amido synthetase from grapevine
      involved in auxin homeostasis.
AB  - Auxins are important for plant growth and development, including the control of
      fruit ripening. Conjugation to amino acids by indole-3-acetic acid (IAA)-amido
      synthetases is an important part of auxin homeostasis. The structure of the auxin
      conjugating Gretchen Hagen3-1 (GH3-1) enzyme from grapevine (Vitis vinifera), in
      complex with an inhibitor (adenosine-5'-[2-(1H-indol-3-yl)ethyl]phosphate), is
      presented. Comparison with a previously published benzoate-conjugating enzyme
      from Arabidopsis thaliana indicates that grapevine GH3-1 has a highly similar
      domain structure and also undergoes a large conformational change during
      catalysis. Mutational analyses and structural comparisons with other proteins
      have identified residues likely to be involved in acyl group, amino acid, and ATP
      substrate binding. Vv GH3-1 is a monomer in solution and requires magnesium ions
      solely for the adenlyation reaction. Modeling of IAA and two synthetic auxins,
      benzothiazole-2-oxyacetic acid (BTOA) and 1-naphthaleneacetic acid (NAA), into
      the active site indicates that NAA and BTOA are likely to be poor substrates for
      this enzyme, confirming previous enzyme kinetic studies. This suggests a reason
      for the increased effectiveness of NAA and BTOA as auxins in planta and provides
      a tool for designing new and effective auxins.

PMID- 23136373
TI  - The novel plant protein INAPERTURATE POLLEN1 marks distinct cellular domains and
      controls formation of apertures in the Arabidopsis pollen exine.
AB  - Pollen grains protect the sperm cells inside them with the help of the unique
      cell wall, the exine, which exhibits enormous morphological variation across
      plant taxa, assembling into intricate and diverse species-specific patterns. How
      this complex extracellular structure is faithfully deposited at precise sites and
      acquires precise shape within a species is not understood. Here, we describe the
      isolation and characterization of the novel Arabidopsis thaliana gene
      INAPERTURATE POLLEN1 (INP1), which is specifically involved in formation of the
      pollen surface apertures, which arise by restriction of exine deposition at
      specific sites. Loss of INP1 leads to the loss of all three apertures in
      Arabidopsis pollen, and INP1 protein exhibits a unique tripartite localization in
      developing pollen, indicative of its direct involvement in specification of
      aperture positions. We also show that aperture length appears to be sensitive to
      INP1 dosage and INP1 misexpression can affect global exine patterning. Phenotypes
      of some inp1 mutants indicate that Arabidopsis apertures are initiated at three
      nonrandom positions around the pollen equator. The identification of INP1 opens
      up new avenues for studies of how formation of distinct cellular domains results
      in the production of different extracellular morphologies.

PMID- 23136374
TI  - NODULE ROOT and COCHLEATA maintain nodule development and are legume orthologs of
      Arabidopsis BLADE-ON-PETIOLE genes.
AB  - During their symbiotic interaction with rhizobia, legume plants develop symbiosis
      specific organs on their roots, called nodules, that house nitrogen-fixing
      bacteria. The molecular mechanisms governing the identity and maintenance of
      these organs are unknown. Using Medicago truncatula nodule root (noot) mutants
      and pea (Pisum sativum) cochleata (coch) mutants, which are characterized by the
      abnormal development of roots from the nodule, we identified the NOOT and COCH
      genes as being necessary for the robust maintenance of nodule identity throughout
      the nodule developmental program. NOOT and COCH are Arabidopsis thaliana BLADE-ON
      PETIOLE orthologs, and we have shown that their functions in leaf and flower
      development are conserved in M. truncatula and pea. The identification of these
      two genes defines a clade in the BTB/POZ-ankyrin domain proteins that shares
      conserved functions in eudicot organ development and suggests that NOOT and COCH
      were recruited to repress root identity in the legume symbiotic organ.

PMID- 23136375
TI  - Genome-wide control of polyadenylation site choice by CPSF30 in Arabidopsis.
AB  - The Arabidopsis thaliana ortholog of the 30-kD subunit of the mammalian Cleavage
      and Polyadenylation Specificity Factor (CPSF30) has been implicated in the
      responses of plants to oxidative stress, suggesting a role for alternative
      polyadenylation. To better understand this, poly(A) site choice was studied in a
      mutant (oxt6) deficient in CPSF30 expression using a genome-scale approach. The
      results indicate that poly(A) site choice in a large majority of Arabidopsis
      genes is altered in the oxt6 mutant. A number of poly(A) sites were identified
      that are seen only in the wild type or oxt6 mutant. Interestingly, putative
      polyadenylation signals associated with sites that are seen only in the oxt6
      mutant are decidedly different from the canonical plant polyadenylation signal,
      lacking the characteristic A-rich near-upstream element (where AAUAAA can be
      found); this suggests that CPSF30 functions in the handling of the near-upstream
      element. The sets of genes that possess sites seen only in the wild type or
      mutant were enriched for those involved in stress and defense responses, a result
      consistent with the properties of the oxt6 mutant. Taken together, these studies
      provide new insights into the mechanisms and consequences of CPSF30-mediated
      alternative polyadenylation.

PMID- 23136376
TI  - The tomato FRUITFULL homologs TDR4/FUL1 and MBP7/FUL2 regulate ethylene
      independent aspects of fruit ripening.
AB  - Tomato (Solanum lycopersicum) contains two close homologs of the Arabidopsis
      thaliana MADS domain transcription factor FRUITFULL (FUL), FUL1 (previously
      called TDR4) and FUL2 (previously MBP7). Both proteins interact with the ripening
      regulator RIPENING INHIBITOR (RIN) and are expressed during fruit ripening. To
      elucidate their function in tomato, we characterized single and double FUL1 and
      FUL2 knockdown lines. Whereas the single lines only showed very mild alterations
      in fruit pigmentation, the double silenced lines exhibited an orange-ripe fruit
      phenotype due to highly reduced lycopene levels, suggesting that FUL1 and FUL2
      have a redundant function in fruit ripening. More detailed analyses of the
      phenotype, transcriptome, and metabolome of the fruits silenced for both FUL1 and
      FUL2 suggest that the genes are involved in cell wall modification, the
      production of cuticle components and volatiles, and glutamic acid (Glu)
      accumulation. Glu is responsible for the characteristic umami taste of the
      present-day cultivated tomato fruit. In contrast with previously identified
      ripening regulators, FUL1 and FUL2 do not regulate ethylene biosynthesis but
      influence ripening in an ethylene-independent manner. Our data combined with
      those of others suggest that FUL1/2 and TOMATO AGAMOUS-LIKE1 regulate different
      subsets of the known RIN targets, probably in a protein complex with the latter.

PMID- 23136378
TI  - TCOPPE school environmental audit tool: assessing safety and walkability of
      school environments.
AB  - BACKGROUND: Several environmental audit instruments have been developed for
      assessing streets, parks and trails, but none for schools. This paper introduces
      a school audit tool that includes 3 subcomponents: 1) street audit, 2) school
      site audit, and 3) map audit. It presents the conceptual basis and the
      development process of this instrument, and the methods and results of the
      reliability assessments. METHODS: Reliability tests were conducted by 2 trained
      auditors on 12 study schools (high-low income and urban-suburban-rural settings).
      Kappa statistics (categorical, factual items) and ICC (Likert-scale, perceptual
      items) were used to assess a) interrater, b) test-retest, and c) peak vs. off
      peak hour reliability tests. RESULTS: For the interrater reliability test, the
      average Kappa was 0.839 and the ICC was 0.602. For the test-retest reliability,
      the average Kappa was 0.903 and the ICC was 0.774. The peak-off peak reliability
      was 0.801. Rural schools showed the most consistent results in the peak-off peak
      and test-retest assessments. For interrater tests, urban schools showed the
      highest ICC, and rural schools showed the highest Kappa. CONCLUSIONS: Most items
      achieved moderate to high levels of reliabilities in all study schools. With
      proper training, this audit can be used to assess school environments reliably
      for research, outreach, and policy-support purposes.

PMID- 23136379
TI  - Introduction: Public policy series--data in nephrology.

PMID- 23136377
TI  - Genome-wide analysis uncovers regulation of long intergenic noncoding RNAs in
      Arabidopsis.
AB  - Long intergenic noncoding RNAs (lincRNAs) transcribed from intergenic regions of
      yeast and animal genomes play important roles in key biological processes. Yet,
      plant lincRNAs remain poorly characterized and how lincRNA biogenesis is
      regulated is unclear. Using a reproducibility-based bioinformatics strategy to
      analyze 200 Arabidopsis thaliana transcriptome data sets, we identified 13,230
      intergenic transcripts of which 6480 can be classified as lincRNAs. Expression of
      2708 lincRNAs was detected by RNA sequencing experiments. Transcriptome profiling
      by custom microarrays revealed that the majority of these lincRNAs are expressed
      at a level between those of mRNAs and precursors of miRNAs. A subset of lincRNA
      genes shows organ-specific expression, whereas others are responsive to biotic
      and/or abiotic stresses. Further analysis of transcriptome data in 11 mutants
      uncovered SERRATE, CAP BINDING PROTEIN20 (CBP20), and CBP80 as regulators of
      lincRNA expression and biogenesis. RT-PCR experiments confirmed these three
      proteins are also needed for splicing of a small group of intron-containing
      lincRNAs.

PMID- 23136380
TI  - Prescribed exercise: a prospective study of health-related quality of life and
      physical fitness among participants in an officially sponsored municipal physical
      training program.
AB  - BACKGROUND: Participants who completed a 3-month prescribed individualized
      exercise program in groups were followed-up prospectively. The aims were to
      describe the characteristics of the participants, their health-related quality of
      life (HRQoL) and physical fitness at baseline, at completion and at 12-month
      follow-up, and to identify predictors of HRQoL and physical fitness at completion
      and at 12-month follow-up. METHODS: A 1-group follow-up design was used. Data
      were collected from records of 163 attendees at a municipality-sponsored health
      center in Norway. HRQoL was measured by self-report using the COOP/WONCA
      questionnaire. Physical fitness was estimated from the results of a 2-km walk
      test. RESULTS: Of the 163 participants referred to the clinic, 130 (79.8%) were
      women and 33 were (20.2%) men. Participants who completed were older than those
      who dropped out. The participants showed clinical improvement in physical fitness
      and all health-related quality life domains (d > 0.53) at the completion of the
      program and in physical functioning, mental health, performance of daily
      activities, overall health, and perceived improved health after 12 months (d >
      0.36). CONCLUSIONS: Participation in group-based prescribed exercise program for
      3 months may improve physical fitness and HRQoL significantly in short and long
      terms.

PMID- 23136381
TI  - Expression dynamics of the Medicago truncatula transcriptome during the symbiotic
      interaction with Sinorhizobium meliloti: which role for nitric oxide?
AB  - Medicago truncatula is one of the most studied model plants. Nevertheless, the
      genome of this legume remains incompletely determined. We used RNA-Seq to
      characterize the transcriptome during the early organogenesis of the nodule and
      during its functioning. We detected 37,333 expressed transcription units; to our
      knowledge, 1,670 had never been described before and were functionally annotated.
      We identified 7,595 new transcribed regions, mostly corresponding to 5' and 3'
      untranslated region extensions and new exons associated with 5,264 previously
      annotated genes. We also inferred 23,165 putative transcript isoforms from 6,587
      genes and measured the abundance of transcripts for each isoform, which suggests
      an important role for alternative splicing in the generation of proteome
      diversity in M. truncatula. Finally, we carried out a differential expression
      analysis, which provided a comprehensive view of transcriptional reprogramming
      during nodulation. In particular, depletion of nitric oxide in roots inoculated
      with Sinorhizobium meliloti greatly increased our understanding of the role of
      this reactive species in the optimal establishment of the symbiotic interaction,
      revealing differential patterns of expression for 2,030 genes and pointing to the
      inhibition of the expression of defense genes.

PMID- 23136383
TI  - Do motivation-related cognitions explain the relationship between perceptions of
      urban form and neighborhood walking?
AB  - BACKGROUND: The built and social environments may contribute to physical activity
      motivations and behavior. We examined the extent to which the Theory of Planned
      Behavior (TPB) mediated the association between neighborhood walkability and
      walking. METHODS: Two random cross-sectional samples (n = 4422 adults) completed
      telephone interviews capturing walking-related TPB variables (perceived
      behavioral control (PBC), attitudes, subjective norm, intention). Of those, 2006
      completed a self-administered questionnaire capturing walkability, social support
      (friends, family, dog ownership), and neighborhood-based transportation (NTW) and
      recreational walking (NRW). The likelihood of undertaking 1) any vs. none and 2)
      sufficient vs. insufficient levels (>=150 vs. <150 minutes/week) of NTW and NWR,
      in relation to walkability, social support, and TPB was estimated. RESULTS: Any
      and sufficient NTW were associated with access to services, connectivity,
      residential density, not owning a dog (any NTW only), and friend and family
      support. Any and sufficient NRW were associated with neighborhood aesthetics (any
      NRW only), dog ownership, and friend and family support. PBC partially mediated
      the association between access to services and NTW (any and sufficient), while
      experiential attitudes partially mediated the association between neighborhood
      aesthetics and any NRW. CONCLUSIONS: Interventions that increase positive
      perceptions of the built environment may motivate adults to undertake more
      walking.

PMID- 23136382
TI  - Rhizobial and mycorrhizal symbioses in Lotus japonicus require lectin nucleotide
      phosphohydrolase, which acts upstream of calcium signaling.
AB  - Nodulation in legumes requires the recognition of rhizobially made Nod factors.
      Genetic studies have revealed that the perception of Nod factors involves LysM
      domain receptor-like kinases, while biochemical approaches have identified LECTIN
      NUCLEOTIDE PHOSPHOHYDROLASE (LNP) as a Nod factor-binding protein. Here, we show
      that antisense inhibition of LNP blocks nodulation in Lotus japonicus. This
      absence of nodulation was due to a defect in Nod factor signaling based on the
      observations that the early nodulation gene NODULE INCEPTION was not induced and
      that both Nod factor-induced perinuclear calcium spiking and calcium influx at
      the root hair tip were blocked. However, Nod factor did induce root hair
      deformation in the LNP antisense lines. LNP is also required for infection by the
      mycorrhizal fungus Glomus intraradices, suggesting that LNP plays a role in the
      common signaling pathway shared by the rhizobial and mycorrhizal symbioses. Taken
      together, these observations indicate that LNP acts at a novel position in the
      early stages of symbiosis signaling. We propose that LNP functions at the
      earliest stage of the common nodulation and mycorrhization symbiosis signaling
      pathway downstream of the Nod factor receptors; it may act either by influencing
      signaling via changes in external nucleotides or in conjunction with the LysM
      receptor-like kinases for recognition of Nod factor.

PMID- 23136384
TI  - Sex-based difference in the perception of exercise and level of physical activity
      among residents of Karachi City, Pakistan.
AB  - OBJECTIVES: To identify sex-based differences in the perception of benefits and
      barriers toward exercise and to determine the sex- and age-based differences in
      the level of physical activity (PA) among adult residents of Karachi. METHODS:
      Three hundred adult individuals were included in cross sectional survey conducted
      during July-October 2010. Perception of benefits and barriers to exercise and the
      level of PA were measured through a questionnaire. Differences in the perception
      of benefits and barriers of exercise and level of PA were calculated with age and
      sex strata. RESULTS: Women perceived more barriers to exercise than men (P-value
      < 0.001). In all age strata women have higher ranks for domestic-related physical
      activity while men have higher ranks for job-related PA. Leisure time PA were
      significantly lower for females in all age groups. Total PA is also affected by
      age and socioeconomic status, higher among people having monthly income < 6000
      rupees and lower in males > 45 years of age. CONCLUSION: Sex-based differences
      exists in the level of PA and perception regarding exercise in mega city of
      Pakistan. There is a need to design programs that influence PA determinants
      connected to sex to prevent impending epidemic of non communicable diseases.

PMID- 23136385
TI  - An exploratory study of seasonality and preschoolers' physical activity
      engagement.
AB  - BACKGROUND: While there is an emerging body of literature showing variations in
      physical activity between seasons, further investigation is needed to better
      understand this association in preschool-age children. This study was designed to
      examine seasonal variation from fall to winter in physical activity among
      preschoolers. METHODS: Forty-six preschool children from 2 preschools in a large
      Midwestern Metropolitan area completed weekly habitual physical activity measures
      in both fall and following winter. The habitual physical activity was quantified
      with the GT1M Actigraph uniaxial accelerometer. To determine seasonal differences
      in physical activity, a series of paired sample t tests were conducted. RESULTS:
      Although overall physical activity level declined in winter, the magnitude of
      seasonality effects seem varied in terms of contexts. Compared with the decline
      during after-school time and during weekends, the differences in physical
      activity across the 2 seasons were much less evident during the time attending
      preschool and during weekdays. CONCLUSION: Seasonality in physical activity can
      be moderated by other contextual factors, such as preschool policies and
      curriculum. Preschools may serve as a major battlefield for fighting against
      physical inactivity and obesity during childhood due to their practical
      controllability.

PMID- 23136386
TI  - Tissue-specific function of Patj in regulating the Crumbs complex and epithelial
      polarity.
AB  - Patj is described as a core component of the Crumbs complex. Along with the other
      components, Crumbs and Stardust, Patj has been proposed as essential for
      epithelial polarity. However, no proper in vivo genetic analysis of Patj function
      has been performed in any organism. We have generated the first null mutants for
      Drosophila Patj. These mutants are lethal. However, Patj is not required in all
      epithelia where the Crumbs complex is essential. Patj is dispensable for ectoderm
      polarity and embryonic development, whereas more severe defects are observed in
      the adult follicular epithelium, including mislocalisation of the Crumbs complex
      from the apical domain, as well as morphogenetic defects. These defects are
      similar to those observed with crumbs and stardust mutants, although weaker and
      less frequent. Also, gain-of-function of Crumbs and Patj mutation genetically
      suppress each other in follicular cells. We also show that the first PDZ domain
      of Patj associated with the Stardust-binding domain are sufficient to fully
      rescue both Drosophila viability and Crumbs localisation. We propose that the
      only crucial function of Patj hinges on the ability of its first two domains to
      positively regulate the Crumbs complex, defining a new developmental level of
      regulation of its dynamics.

PMID- 23136387
TI  - Shroom3 is required downstream of FGF signalling to mediate proneuromast assembly
      in zebrafish.
AB  - During development, morphogenetic processes require a precise coordination of
      cell differentiation, cell shape changes and, often, cell migration. Yet, how
      pattern information is used to orchestrate these different processes is still
      unclear. During lateral line (LL) morphogenesis, a group of cells simultaneously
      migrate and assemble radially organized cell clusters, termed rosettes, that
      prefigure LL sensory organs. This process is controlled by Fibroblast growth
      factor (FGF) signalling, which induces cell fate changes, cell migration and cell
      shape changes. However, the exact molecular mechanisms induced by FGF activation
      that mediate these changes on a cellular level are not known. Here, we focus on
      the mechanisms by which FGFs control apical constriction and rosette assembly. We
      show that apical constriction in the LL primordium requires the activity of non
      muscle myosin. We demonstrate further that shroom3, a well-known regulator of non
      muscle myosin activity, is expressed in the LL primordium and that its expression
      requires FGF signalling. Using gain- and loss-of-function experiments, we
      demonstrate that Shroom3 is the main organizer of cell shape changes during
      rosette assembly, probably by coordinating Rho kinase recruitment and non-muscle
      myosin activation. In order to quantify morphogenesis in the LL primordium in an
      unbiased manner, we developed a unique trainable 'rosette detector'. We thus
      propose a model in which Shroom3 drives rosette assembly in the LL downstream of
      FGF in a Rho kinase- and non-muscle myosin-dependent manner. In conclusion, we
      uncovered the first mechanistic link between patterning and morphogenesis during
      LL sensory organ formation.

PMID- 23136388
TI  - Transcription factor AP-2gamma is a core regulator of tight junction biogenesis
      and cavity formation during mouse early embryogenesis.
AB  - The trophectoderm epithelium is the first differentiated cell layer to arise
      during mammalian development. Blastocyst formation requires the proper expression
      and localization of tight junction, polarity, ion gradient and H2O channel
      proteins in the outer cell membranes. However, the underlying transcriptional
      mechanisms that control their expression are largely unknown. Here, we report
      that transcription factor AP-2gamma (Tcfap2c) is a core regulator of blastocyst
      formation in mice. Bioinformatics, chromatin immunoprecipitation and
      transcriptional analysis revealed that Tcfap2c binds and regulates a diverse
      group of genes expressed during blastocyst formation. RNA interference
      experiments demonstrated that Tcfap2c regulates genes important for tight
      junctions, cell polarity and fluid accumulation. Functional and ultrastructural
      studies revealed that Tcfap2c is necessary for tight junction assembly and
      paracellular sealing in trophectoderm epithelium. Aggregation of control eight
      cell embryos with Tcfap2c knockdown embryos rescued blastocyst formation via
      direct contribution to the trophectoderm epithelium. Finally, we found that
      Tcfap2c promotes cellular proliferation via direct repression of p21
      transcription during the morula-to-blastocyst transition. We propose a model in
      which Tcfap2c acts in a hierarchy to facilitate blastocyst formation through
      transcriptional regulation of core genes involved in tight junction assembly,
      fluid accumulation and cellular proliferation.

PMID- 23136389
TI  - Prdm14 acts upstream of islet2 transcription to regulate axon growth of primary
      motoneurons in zebrafish.
AB  - The precise formation of three-dimensional motor circuits is essential for
      movement control. Within these circuits, motoneurons (MNs) are specified from
      spinal progenitors by dorsoventral signals and distinct transcriptional programs.
      Different MN subpopulations have stereotypic cell body positions and show
      specific spatial axon trajectories. Our knowledge of MN axon outgrowth remains
      incomplete. Here, we report a zebrafish gene-trap mutant, short lightning (slg),
      in which prdm14 expression is disrupted. slg mutant embryos show shortened axons
      in caudal primary (CaP) MNs resulting in defective embryonic movement. Both the
      CaP neuronal defects and behavior abnormality of the mutants can be phenocopied
      by injection of a prdm14 morpholino into wild-type embryos. By removing a copy of
      the inserted transposon from homozygous mutants, prdm14 expression and normal
      embryonic movement were restored, confirming that loss of prdm14 expression
      accounts for the observed defects. Mechanistically, Prdm14 protein binds to the
      promoter region of islet2, a known transcription factor required for CaP
      development. Notably, disruption of islet2 function caused similar CaP axon
      outgrowth defects as observed in slg mutant embryos. Furthermore, overexpression
      of islet2 in slg mutant embryos rescued the shortened CaP axon phenotypes.
      Together, these data reveal that prdm14 regulates CaP axon outgrowth through
      activation of islet2 expression.

PMID- 23136390
TI  - The PBAP remodeling complex is required for histone H3.3 replacement at chromatin
      boundaries and for boundary functions.
AB  - Establishment and maintenance of epigenetic memories are essential for
      development. Replacement of canonical histone H3 by its variant H3.3 has been
      implicated in cellular memory. Drosophila sequence-specific DNA-binding protein
      GAGA factor and a chromatin factor FACT direct H3.3 replacement in conjunction
      with H3.3-specific chaperone HIRA at chromatin boundaries to counteract the
      spreading of silent chromatin. However, little is known about which ATP-driven
      chromatin remodeling factor is responsible for the H3.3 replacement at chromatin
      boundaries. Here, we report that GAGA factor associates with the Polybromo
      associated Brm (PBAP) remodeling complex, which consists of many Trithorax group
      proteins, and recruits this complex to chromatin boundaries d1 (which is
      downstream of w), the Fab-7 DNase-hypersensitive site (HS) 1 of Abd-B and the bxd
      region of Ubx. Trl-encoding GAGA factor, brm and polybromo/bap180 mutations
      compromise the H3.3 replacement and boundary functions in a synergistic manner.
      Furthermore, Polybromo is necessary for generation of the DNase HS at d1, and
      HIRA functions to restore the alteration. Taken together, we propose that FACT
      and PBAP complexes are recruited to chromatin boundaries in a GAGA factor
      dependent manner, and are needed for H3.3 replacement to execute boundary
      functions. Our results provide new insight into the function of the trithorax
      group during development.

PMID- 23136391
TI  - Gbx2 regulates thalamocortical axon guidance by modifying the LIM and Robo codes.
AB  - Combinatorial expression of transcription factors forms transcriptional codes to
      confer neuronal identities and connectivity. However, how these intrinsic factors
      orchestrate the spatiotemporal expression of guidance molecules to dictate the
      responsiveness of axons to guidance cues is less understood. Thalamocortical
      axons (TCAs) represent the major input to the neocortex and modulate cognitive
      functions, consciousness and alertness. TCAs travel a long distance and make
      multiple target choices en route to the cortex. The homeodomain transcription
      factor Gbx2 is essential for TCA development, as loss of Gbx2 abolishes TCAs in
      mice. Using a novel TCA-specific reporter, we have discovered that thalamic axons
      are mostly misrouted to the ventral midbrain and dorsal midline of the
      diencephalon in Gbx2-deficient mice. Furthermore, conditionally deleting Gbx2 at
      different embryonic stages has revealed a sustained role of Gbx2 in regulating
      TCA navigation and targeting. Using explant culture and mosaic analyses, we
      demonstrate that Gbx2 controls the intrinsic responsiveness of TCAs to guidance
      cues. The guidance defects of Gbx2-deficient TCAs are associated with abnormal
      expression of guidance receptors Robo1 and Robo2. Finally, we demonstrate that
      Gbx2 controls Robo expression by regulating LIM-domain transcription factors
      through three different mechanisms: Gbx2 and Lhx2 compete for binding to the Lmo3
      promoter and exert opposing effects on its transcription; repressing Lmo3 by Gbx2
      is essential for Lhx2 activity to induce Robo2; and Gbx2 represses Lhx9
      transcription, which in turn induces Robo1. Our findings illustrate the
      transcriptional control of differential expression of Robo1 and Robo2, which may
      play an important role in establishing the topography of TCAs.

PMID- 23136392
TI  - Frs2alpha enhances fibroblast growth factor-mediated survival and differentiation
      in lens development.
AB  - Most growth factor receptor tyrosine kinases (RTKs) signal through similar
      intracellular pathways, but they often have divergent biological effects.
      Therefore, elucidating the mechanism of channeling the intracellular effect of
      RTK stimulation to facilitate specific biological responses represents a
      fundamental biological challenge. Lens epithelial cells express numerous RTKs
      with the ability to initiate the phosphorylation (activation) of Erk1/2 and PI3
      K/Akt signaling. However, only Fgfr stimulation leads to lens fiber cell
      differentiation in the developing mammalian embryo. Additionally, within the
      lens, only Fgfrs activate the signal transduction molecule Frs2alpha. Loss of
      Frs2alpha in the lens significantly increases apoptosis and decreases
      phosphorylation of both Erk1/2 and Akt. Also, Frs2alpha deficiency decreases the
      expression of several proteins characteristic of lens fiber cell differentiation,
      including Prox1, p57(KIP2), aquaporin 0 and beta-crystallins. Although not
      normally expressed in the lens, the RTK TrkC phosphorylates Frs2alpha in response
      to binding the ligand NT3. Transgenic lens epithelial cells expressing both TrkC
      and NT3 exhibit several features characteristic of lens fiber cells. These
      include elongation, increased Erk1/2 and Akt phosphorylation, and the expression
      of beta-crystallins. All these characteristics of NT3-TrkC transgenic lens
      epithelial cells depend on Frs2alpha. Therefore, tyrosine phosphorylation of
      Frs2alpha mediates Fgfr-dependent lens cell survival and provides a mechanistic
      basis for the unique fiber-differentiating capacity of Fgfs on mammalian lens
      epithelial cells.

PMID- 23136393
TI  - Polo-mediated phosphorylation of Maelstrom regulates oocyte determination during
      oogenesis in Drosophila.
AB  - In Drosophila, Maelstrom is a conserved component of the perinuclear nuage, a
      germline-unique structure that appears to serve as a site for Piwi-interacting
      RNA (piRNA) production to repress deleterious transposons. Maelstrom also
      functions in the nucleus as a transcriptional regulator to repress the expression
      of microRNA-7, a process that is essential for the proper differentiation of
      germline stem cells. In this paper, we report another function of Maelstrom in
      regulating oocyte determination independently of its transposon silencing and
      germline stem cell differentiation activities. In Drosophila, the conserved
      serine 138 residue in Maelstrom is required for its phosphorylation, an event
      that promotes oocyte determination. Phosphorylation of Maelstrom is required for
      the repression of the pachytene checkpoint protein Sir2, but not for transposon
      silencing or for germline stem cell differentiation. We identify Polo as a kinase
      that mediates the phosphorylation of Maelstrom. Our results suggest that the Polo
      mediated phosphorylation of Maelstrom may be a mechanism that controls oocyte
      determination by inactivating the pachytene checkpoint via the repression of Sir2
      in Drosophila ovaries.

PMID- 23136394
TI  - Cell-autonomous Notch activity maintains the temporal specification potential of
      skeletal muscle stem cells.
AB  - During organogenesis, a continuum of founder stem cells produces temporally
      distinct progeny until development is complete. Similarly, in skeletal
      myogenesis, phenotypically and functionally distinct myoblasts and differentiated
      cells are generated during development. How this occurs in muscle and other
      tissues in vertebrates remains largely unclear. We showed previously that
      committed cells are required for maintaining muscle stem cells. Here we show that
      active Notch signalling specifies a subpopulation of myogenic cells with high
      Pax7 expression. By genetically modulating Notch activity, we demonstrate that
      activated Notch (NICD) blocks terminal differentiation in an Rbpj-dependent
      manner that is sufficient to sustain stem/progenitor cells throughout
      embryogenesis, despite the absence of committed progeny. Although arrested in
      lineage progression, NICD-expressing cells of embryonic origin progressively
      mature and adopt characteristics of foetal myogenic cells, including expression
      of the foetal myogenesis regulator Nfix. siRNA-mediated silencing of NICD
      promotes the temporally appropriate foetal myogenic fate in spite of expression
      of markers for multiple cell types. We uncover a differential effect of Notch,
      whereby high Notch activity is associated with stem/progenitor cell expansion in
      the mouse embryo, yet it promotes reversible cell cycle exit in the foetus and
      the appearance of an adult muscle stem cell state. We propose that active Notch
      signalling is sufficient to sustain an upstream population of muscle founder stem
      cells while suppressing differentiation. Significantly, Notch does not override
      other signals that promote temporal myogenic cell fates during ontology where
      spatiotemporal developmental cues produce distinct phenotypic classes of
      myoblasts.

PMID- 23136395
TI  - In vivo evidence for the crucial role of SF1 in steroid-producing cells of the
      testis, ovary and adrenal gland.
AB  - Adrenal and gonadal steroids are essential for life and reproduction. The orphan
      nuclear receptor SF1 (NR5A1) has been shown to regulate the expression of enzymes
      involved in steroid production in vitro. However, the in vivo role of this
      transcription factor in steroidogenesis has not been elucidated. In this study,
      we have generated steroidogenic-specific Cre-expressing mice to lineage mark and
      delete Sf1 in differentiated steroid-producing cells of the testis, the ovary and
      the adrenal gland. Our data show that SF1 is a regulator of the expression of
      steroidogenic genes in all three organs. In addition, Sf1 deletion leads to a
      radical change in cell morphology and loss of identity. Surprisingly, sexual
      development and reproduction in mutant animals were not compromised owing, in
      part, to the presence of a small proportion of SF1-positive cells. In contrast to
      the testis and ovary, the mutant adult adrenal gland showed a lack of Sf1-deleted
      cells and our studies suggest that steroidogenic adrenal cells during foetal
      stages require Sf1 to give rise to the adult adrenal population. This study is
      the first to show the in vivo requirements of SF1 in steroidogenesis and provides
      novel data on the cellular consequences of the loss of this protein specifically
      within steroid-producing cells.

PMID- 23136396
TI  - Neurons and cardiomyocytes derived from induced pluripotent stem cells as a model
      for mitochondrial defects in Friedreich's ataxia.
AB  - Friedreich's ataxia (FRDA) is a recessive neurodegenerative disorder commonly
      associated with hypertrophic cardiomyopathy. FRDA is due to expanded GAA repeats
      within the first intron of the gene encoding frataxin, a conserved mitochondrial
      protein involved in iron-sulphur cluster biosynthesis. This mutation leads to
      partial gene silencing and substantial reduction of the frataxin level. To
      overcome limitations of current cellular models of FRDA, we derived induced
      pluripotent stem cells (iPSCs) from two FRDA patients and successfully
      differentiated them into neurons and cardiomyocytes, two affected cell types in
      FRDA. All FRDA iPSC lines displayed expanded GAA alleles prone to high
      instability and decreased levels of frataxin, but no biochemical phenotype was
      observed. Interestingly, both FRDA iPSC-derived neurons and cardiomyocytes
      exhibited signs of impaired mitochondrial function, with decreased mitochondrial
      membrane potential and progressive mitochondrial degeneration, respectively. Our
      data show for the first time that FRDA iPSCs and their neuronal and cardiac
      derivatives represent promising models for the study of mitochondrial damage and
      GAA expansion instability in FRDA.

PMID- 23136397
TI  - Reduction of pro-tumorigenic activity of human prostate cancer-associated
      fibroblasts using Dlk1 or SCUBE1.
AB  - Human prostatic cancer-associated fibroblasts (CAFs) can elicit malignant changes
      in initiated but non-tumorigenic human prostate epithelium, demonstrating that
      they possess pro-tumorigenic properties. We set out to reduce the pro-tumorigenic
      activity of patient CAFs using the Dlk1 and SCUBE1 molecules that we had
      previously identified in prostate development. Our hypothesis was that
      mesenchymally expressed molecules might reduce CAF pro-tumorigenic activity,
      either directly or indirectly. We isolated primary prostatic CAFs and
      characterised their expression of CAF markers, expression of Notch2, Dlk1 and
      SCUBE1 transcripts, and confirmed their ability to stimulate BPH1 epithelial cell
      proliferation. Next, we expressed Dlk1 or SCUBE1 in CAFs and determined their
      effects upon tumorigenesis in vivo following recombination with BPH1 epithelia
      and xenografting in SCID mice. Tumour size was reduced by about 75% and BPH1
      proliferation was reduced by about 50% after expression of Dlk1 or SCUBE1 in
      CAFs, and there was also a reduction in invasion of BPH1 epithelia into the host
      kidney. Inhibition of Notch signalling, using inhibitor XIX, led to a reduction
      in BPH1 cell proliferation in CAF-BPH1 co-cultures, whereas inhibition of Dlk1 in
      NIH3T3-conditioned media led to an increase in BPH1 growth. Our results suggest
      that pro-tumorigenic CAF activity can be reduced by the expression of
      developmental pathways.

PMID- 23136398
TI  - Moving specialised medicines out of hospital?

PMID- 23136399
TI  - Deciding when to stop: towards evidence-based deprescribing of drugs in older
      populations.
AB  - Minimising the harm from inappropriate prescribing in older populations is a
      major urgent concern for modern healthcare systems. In everyday encounters
      between prescribers and patients, opportunities should be taken to identify
      patients at high risk of harm from polypharmacy and reappraise their need for
      specific drugs. Attempts to reconcile life expectancy, comorbidity burden, care
      goals and patient preferences with the benefits and harms of medications should
      be made in every patient at significant risk. Drugs identified by this process of
      reconciliation as conferring little or no benefit and/or excessive risk of harm
      should be candidates for discontinuation. Evidence supporting a structured
      approach to drug discontinuation (or deprescribing) is emerging, and while many
      barriers to deprescribing exist in routine practice, various enabling strategies
      can help overcome them. 

PMID- 23136400
TI  - Optimal duration of clopidogrel therapy: the shorter the longer?

PMID- 23136401
TI  - Right bundle branch block: are we looking in the right direction?

PMID- 23136402
TI  - ABCA1 mutation carriers with low high-density lipoprotein cholesterol are
      characterized by a larger atherosclerotic burden.
AB  - AIMS: Low HDL-C is a potent risk factor for cardiovascular disease (CVD). Yet,
      mutations in ABCA1, a major determinant of circulating HDL-C levels, were
      previously not associated with CVD risk in cohort studies. To study the
      consequences of low plasma levels of high-density lipoprotein cholesterol (HDL-C)
      due to ATP-binding cassette transporter A1 (ABCA1) dysfunction for
      atherosclerotic vascular disease in the carotid arteries. METHODS AND RESULTS: We
      performed 3.0 Tesla magnetic resonance imaging (MRI) measurements of the carotid
      arteries in 36 carriers of high impact functional ABCA1 mutations and 36
      normolipidemic controls. Carriers presented with 42% lower HDL-C levels (P <
      0.001), a larger mean wall area (18.6 +/- 6.0 vs. 15.8 +/- 4.3 mm(2); P = 0.02),
      a larger mean wall thickness (0.82 +/- 0.21 vs. 0.70 +/- 0.14 mm; P = 0.005), and
      a higher normalized wall index (0.37 +/- 0.06 vs. 0.33 +/- 0.04; P = 0.005)
      compared with controls, retaining significance after adjustment for smoking,
      alcohol consumption, systolic blood pressure, diabetes, body mass index, history
      of CVD, LDL-C, and statin use (P = 0.002). CONCLUSION: Carriers of loss of
      function ABCA1 mutations display a larger atherosclerotic burden compared with
      age and sex-matched controls, implying a higher risk for CVD. Further studies are
      needed to elucidate the full function of ABCA1 in the protection against
      atherosclerosis. These data support the development of strategies to up-regulate
      ABCA1 in patients with established CVD.

PMID- 23136403
TI  - Mutations in the area composita protein alphaT-catenin are associated with
      arrhythmogenic right ventricular cardiomyopathy.
AB  - AIMS: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a major cause of
      juvenile sudden death and is characterized by fibro-fatty replacement of the
      right ventricle. Mutations in several genes encoding desmosomal proteins have
      been identified in ARVC. We speculated that alphaT-catenin, encoded by CTNNA3,
      might also carry mutations in ARVC patients. Alpha-T-catenin binds plakophilins
      and this binding contributes to the formation of the area composita, which
      strengthens cell-cell adhesion in contractile cardiomyocytes. METHODS AND
      RESULTS: We used denaturing high-performance liquid chromatography and direct
      sequencing to screen CTNNA3 in 76 ARVC patients who did not carry any mutations
      in the desmosomal genes commonly mutated in ARVC. Mutations c.281T > A (p.V94D)
      and c.2293_2295delTTG (p.del765L) were identified in two probands. They are
      located in important domains of alphaT-catenin. Yeast two-hybrid and cell
      transfection studies showed that the interaction between the p.V94D mutant
      protein and beta-catenin was affected, whereas the p.del765L mutant protein
      showed a much stronger dimerization potential and formed aggresomes in HEK293T
      cells. CONCLUSION: These findings might point to a causal relationship between
      CTNNA3 mutations and ARVC. This first report on the involvement of an area
      composita gene in ARVC shows that the pathogenesis of this disease extends beyond
      desmosomes. Since the frequency of CTNNA3 mutations in ARVC patients is not rare,
      systematic screening for this gene should be considered to improve the clinical
      management of ARVC families.

PMID- 23136404
TI  - Association of proinsulin and hepatic steatosis in a random, population-based
      sample.
AB  - OBJECTIVE: Proinsulin may represent a predictive marker for assessing insulin
      resistance and reduced beta-cell function. The objective of this study was to
      investigate the association between hepatic steatosis, proinsulin and other
      parameters in a random, population-based sample. DESIGN: Cross-sectional study,
      conducted in south-western Germany. METHODS: Upper abdominal ultrasound
      examinations were performed in 343 subjects (147 females, 196 males; average age
      40.0+/-11.5 years). Proinsulin, the proinsulin-to-insulin ratio and other
      laboratory parameters were determined, and the BMI, waist-to-hip ratio (WHR) and
      other anthropometric data were documented. RESULTS: HEPATIC STEATOSIS WAS
      OBSERVED IN 80 SUBJECTS (23.3%: 29.6%, males; 15.0%, females). Multivariate
      analysis showed an association with hepatic steatosis for male gender (P=0.0212),
      advancing age (P=0.0241), elevated BMI (P<0.0001), elevated WHR (P=0.0024),
      alanine aminotransferase (P=0.0046), proinsulin (P=0.0403) and proinsulin-to
      insulin ratio (P=0.0116). CONCLUSIONS: There is an association between elevated
      proinsulin concentrations and hepatic steatosis.

PMID- 23136405
TI  - Motor axonal regeneration following cord transection.

PMID- 23136406
TI  - Dorsomedial prefrontal cortex mediates rapid evaluations predicting the outcome
      of romantic interactions.
AB  - Humans frequently make real-world decisions based on rapid evaluations of minimal
      information; for example, should we talk to an attractive stranger at a party?
      Little is known, however, about how the brain makes rapid evaluations with real
      and immediate social consequences. To address this question, we scanned
      participants with functional magnetic resonance imaging (fMRI) while they viewed
      photos of individuals that they subsequently met at real-life "speed-dating"
      events. Neural activity in two areas of dorsomedial prefrontal cortex (DMPFC),
      paracingulate cortex, and rostromedial prefrontal cortex (RMPFC) was predictive
      of whether each individual would be ultimately pursued for a romantic
      relationship or rejected. Activity in these areas was attributable to two
      distinct components of romantic evaluation: either consensus judgments about
      physical beauty (paracingulate cortex) or individualized preferences based on a
      partner's perceived personality (RMPFC). These data identify novel computational
      roles for these regions of the DMPFC in even very rapid social evaluations. Even
      a first glance, then, can accurately predict romantic desire, but that glance
      involves a mix of physical and psychological judgments that depend on specific
      regions of DMPFC.

PMID- 23136407
TI  - Effective deep brain stimulation suppresses low-frequency network oscillations in
      the basal ganglia by regularizing neural firing patterns.
AB  - Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective
      treatment for the motor symptoms of Parkinson's disease (PD). The effects of DBS
      depend strongly on stimulation frequency: high frequencies (>90 Hz) improve motor
      symptoms, while low frequencies (<50 Hz) are either ineffective or exacerbate
      symptoms. The neuronal basis for these frequency-dependent effects of DBS is
      unclear. The effects of different frequencies of STN-DBS on behavior and single
      unit neuronal activity in the basal ganglia were studied in the unilateral 6
      hydroxydopamine lesioned rat model of PD. Only high-frequency DBS reversed motor
      symptoms, and the effectiveness of DBS depended strongly on stimulation frequency
      in a manner reminiscent of its clinical effects in persons with PD.
      Quantification of single-unit activity in the globus pallidus externa (GPe) and
      substantia nigra reticulata (SNr) revealed that high-frequency DBS, but not low
      frequency DBS, reduced pathological low-frequency oscillations (~9 Hz) and
      entrained neurons to fire at the stimulation frequency. Similarly, the coherence
      between simultaneously recorded pairs of neurons within and across GPe and SNr
      shifted from the pathological low-frequency band to the stimulation frequency
      during high-frequency DBS, but not during low-frequency DBS. The changes in
      firing patterns in basal ganglia neurons were not correlated with changes in
      firing rate. These results indicate that high-frequency DBS is more effective
      than low-frequency DBS, not as a result of changes in firing rate, but rather due
      to its ability to replace pathological low-frequency network oscillations with a
      regularized pattern of neuronal firing.

PMID- 23136408
TI  - The neural correlates of recollection: transient versus sustained FMRI effects.
AB  - Prior research has identified several regions where neural activity is enhanced
      when recollection of episodic information is successful. Here, we investigated
      whether these regions dissociate according to whether recollection-related
      activity is transient or sustained across the time that recollected information
      must be maintained before a behavioral judgment. Human subjects studied a series
      of word-picture pairs under the requirement to judge which of the denoted objects
      was smaller. Following each of 4 study sessions, a scanned test phase occurred in
      which a series of studied and unstudied words was presented. The requirement at
      test was to judge whether each word was old or new and, if judged old, to
      retrieve the associated study picture and hold it in mind until a cue appeared.
      The delay interval varied between two and eight seconds. The cue instructed
      subjects which of three different judgments should be applied to the retrieved
      picture. Separate responses were required when words were either deemed new or
      the associated image was not retrieved. Relative to studied words for which the
      associated picture could not be retrieved, words giving rise to successful
      recollection elicited transient responses in the hippocampus/parahippocampal
      cortex and retrosplenial cortex, and to sustained activity in prefrontal cortex,
      the intraparietal sulcus, the left angular gyrus and the inferior temporal gyrus.
      The finding that recollection-related activity in the angular gyrus tracked the
      period over which recollected information was maintained is consistent with the
      proposal that this region contributes to the online representation of recollected
      information.

PMID- 23136409
TI  - Clustered fine compartmentalization of the mouse embryonic cerebellar cortex and
      its rearrangement into the postnatal striped configuration.
AB  - Compartmentalization is essential for a brain area to be involved in different
      functions through topographic afferent and efferent connections that reflect this
      organization. The adult cerebellar cortex is compartmentalized into longitudinal
      stripes, in which Purkinje cells (PCs) have compartment-specific molecular
      expression profiles. How these compartments form during development is generally
      not understood. To investigate this process, we focused on the late developmental
      stages of the cerebellar compartmentalization that occur from embryonic day 17.5
      (E17.5), when embryonic compartmentalization is evidently observed, to postnatal
      day 6 (P6), when adult-type compartmentalization begins to be established. The
      transformation between these compartmentalization patterns was analyzed by
      mapping expression patterns of several key molecular markers in serial cerebellar
      sections in the mouse. A complete set of 54 clustered PC subsets, which had
      different expression profiles of FoxP2, PLCbeta4, EphA4, Pcdh10, and a reporter
      molecule of the 1NM13 transgenic mouse strain, were distinguished in three
      dimensional space in the E17.5 cerebellum. Following individual PC subsets during
      development indicated that these subsets were rearranged from a clustered and
      multilayered configuration to a flattened, single-layered and striped
      configuration by means of transverse slide, longitudinal split, or transverse
      twist spatial transformations during development. The Purkinje cell-free spaces
      that exist between clusters at E17.5 become granule cell raphes that separate
      striped compartments at P6. The results indicate that the ~50 PC clusters of the
      embryonic cerebellum will ultimately become the longitudinal compartments of the
      adult cerebellum after undergoing various peri- and postnatal transformations
      that alter their relative spatial relationships.

PMID- 23136410
TI  - Impaired autophagy in neurons after disinhibition of mammalian target of
      rapamycin and its contribution to epileptogenesis.
AB  - Certain mutations within the mammalian target of rapamycin (mTOR) pathway, most
      notably those affecting the tuberous sclerosis complex (TSC), lead to aberrant
      activation of mTOR and result in a high incidence of epilepsy in humans and
      animal models. Although hyperactivation of mTOR has been strongly linked to the
      development of epilepsy and, conversely, inhibition of mTOR by rapamycin
      treatment is protective against seizures in several models, the downstream
      epileptic mechanisms have remained elusive. Autophagy, a catabolic process that
      plays a vital role in cellular homeostasis by mediating the turnover of
      cytoplasmic constituents, is negatively regulated by mTOR. Here we demonstrate
      that autophagy is suppressed in brain tissues of forebrain-specific conditional
      TSC1 and phosphatase and tensin homlog knock-out mice, both of which display
      aberrant mTOR activation and seizures. In addition, we also discovered that
      autophagy is suppressed in the brains of human TSC patients. Moreover,
      conditional deletion of Atg7, an essential regulator of autophagy, in mouse
      forebrain neurons is sufficient to promote development of spontaneous seizures.
      Thus, our study suggests that impaired autophagy contributes to epileptogenesis,
      which may be of interest as a potential therapeutic target for epilepsy treatment
      and/or prevention.

PMID- 23136411
TI  - Conditional Mullercell ablation causes independent neuronal and vascular
      pathologies in a novel transgenic model.
AB  - Muller cells are the major glia of the retina that serve numerous functions
      essential to retinal homeostasis, yet the contribution of Muller glial
      dysfunction to retinal diseases remains largely unknown. We have developed a
      transgenic model using a portion of the regulatory region of the retinaldehyde
      binding protein 1 gene for conditional Muller cell ablation and the consequences
      of primary Muller cell dysfunction have been studied in adult mice. We found that
      selective ablation of Muller cells led to photoreceptor apoptosis, vascular
      telangiectasis, blood-retinal barrier breakdown and, later, intraretinal
      neovascularization. These changes were accompanied by impaired retinal function
      and an imbalance between vascular endothelial growth factor-A (VEGF-A) and
      pigment epithelium-derived factor. Intravitreal injection of ciliary neurotrophic
      factor inhibited photoreceptor injury but had no effect on the vasculopathy.
      Conversely, inhibition of VEGF-A activity attenuated vascular leak but did not
      protect photoreceptors. Our findings show that Muller glial deficiency may be an
      important upstream cause of retinal neuronal and vascular pathologies in retinal
      diseases. Combined neuroprotective and anti-angiogenic therapies may be required
      to treat Muller cell deficiency in retinal diseases and in other parts of the CNS
      associated with glial dysfunction.

PMID- 23136412
TI  - Conceptual object representations in human anterior temporal cortex.
AB  - Interaction with everyday objects requires the representation of conceptual
      object properties, such as where and how an object is used. What are the neural
      mechanisms that support this knowledge? While research on semantic dementia has
      provided evidence for a critical role of the anterior temporal lobes (ATLs) in
      object knowledge, fMRI studies using univariate analysis have primarily
      implicated regions outside the ATL. In the present human fMRI study we used
      multivoxel pattern analysis to test whether activity patterns in ATLs carry
      information about conceptual object properties. Participants viewed objects that
      differed on two dimensions: where the object is typically found (in the kitchen
      or the garage) and how the object is commonly used (with a rotate or a squeeze
      movement). Anatomical region-of-interest analyses covering the ventral visual
      stream revealed that information about the location and action dimensions
      increased from posterior to anterior ventral temporal cortex, peaking in the
      temporal pole. Whole-brain multivoxel searchlight analysis confirmed these
      results, revealing highly significant and regionally specific information about
      the location and action dimensions in the anterior temporal lobes bilaterally. In
      contrast to conceptual object properties, perceptual and low-level visual
      properties of the objects were reflected in activity patterns in posterior
      lateral occipitotemporal cortex and occipital cortex, respectively. These results
      provide fMRI evidence that object representations in the anterior temporal lobes
      are abstracted away from perceptual properties, categorizing objects in
      semantically meaningful groups to support conceptual object knowledge.

PMID- 23136413
TI  - Action potential-independent and pharmacologically unique vesicular serotonin
      release from dendrites.
AB  - Serotonin released within the dorsal raphe nucleus (DR) induces feedback
      inhibition of serotonin neuron activity and consequently regulates mood
      controlling serotonin release throughout the forebrain. Serotonin packaged in
      vesicles is released in response to action potentials by the serotonin neuron
      soma and terminals, but the potential for release by dendrites is unknown. Here,
      three-photon microscopy imaging of endogenous serotonin in living rat brain
      slice, immunofluorescence, and immunogold electron microscopy detection of VMAT2
      (vesicular monoamine transporter 2) establish the presence of vesicular serotonin
      within DR dendrites. Furthermore, activation of glutamate receptors is shown to
      induce vesicular serotonin release from dendrites. However, unlike release from
      the soma and terminals, dendritic serotonin release is independent of action
      potentials, relies on L-type Ca(2+) channels, is induced preferentially by NMDA,
      and displays distinct sensitivity to the selective serotonin reuptake inhibitor
      (SSRI) antidepressant fluoxetine. The unique control of dendritic serotonin
      release has important implications for DR physiology and the antidepressant
      action of SSRIs, dihydropyridines, and NMDA receptor antagonists.

PMID- 23136414
TI  - Searching for the mismatch negativity in primary auditory cortex of the awake
      monkey: deviance detection or stimulus specific adaptation?
AB  - The mismatch negativity (MMN) is a preattentive component of the auditory event
      related potential that is elicited by a change in a repetitive acoustic pattern.
      While MMN has been extensively used in human electrophysiological studies of
      auditory processing, the neural mechanisms and brain regions underlying its
      generation remain unclear. We investigate possible homologs of the MMN in macaque
      primary auditory cortex (A1) using a frequency oddball paradigm in which rare
      "deviant" tones are randomly interspersed among frequent "standard" tones.
      Standards and deviants had frequencies equal to the best frequency (BF) of the
      recorded neural population or to a frequency that evoked a response half the
      amplitude of the BF response. Early and later field potentials, current source
      density components, multiunit activity, and induced high-gamma band responses
      were larger when elicited by deviants than by standards of the same frequency.
      Laminar analysis indicated that differences between deviant and standard
      responses were more prominent in later activity, thus suggesting cortical
      amplification of initial responses driven by thalamocortical inputs. However,
      unlike the human MMN, larger deviant responses were characterized by the
      enhancement of "obligatory" responses rather than the introduction of new
      components. Furthermore, a control condition wherein deviants were interspersed
      among many tones of variable frequency replicated the larger responses to
      deviants under the oddball condition. Results suggest that differential responses
      under the oddball condition in macaque A1 reflect stimulus-specific adaptation
      rather than deviance detection per se. We conclude that neural mechanisms of
      deviance detection likely reside in cortical areas outside of A1.

PMID- 23136415
TI  - Gene expression identifies distinct ascending glutamatergic pathways to frequency
      organized auditory cortex in the rat brain.
AB  - A conserved feature of sound processing across species is the presence of
      multiple auditory cortical fields with topographically organized responses to
      sound frequency. Current organizational schemes propose that the ventral division
      of the medial geniculate body (MGBv) is a single functionally homogenous
      structure that provides the primary source of input to all neighboring frequency
      organized cortical fields. These schemes fail to account for the contribution of
      MGBv to functional diversity between frequency-organized cortical fields. Here,
      we report response property differences for two auditory fields in the rat, and
      find they have nonoverlapping sources of thalamic input from the MGBv that are
      distinguished by the gene expression for type 1 vesicular glutamate transporter.
      These data challenge widely accepted organizational schemes and demonstrate a
      genetic plurality in the ascending glutamatergic pathways to frequency-organized
      auditory cortex.

PMID- 23136416
TI  - Stimulation of electro-olfactogram responses in the main olfactory epithelia by
      airflow depends on the type 3 adenylyl cyclase.
AB  - Cilia of olfactory sensory neurons are the primary sensory organelles for
      olfaction. The detection of odorants by the main olfactory epithelium (MOE)
      depends on coupling of odorant receptors to the type 3 adenylyl cyclase (AC3) in
      olfactory cilia. We monitored the effect of airflow on electro-olfactogram (EOG)
      responses and found that the MOE of mice can sense mechanical forces generated by
      airflow. The airflow-sensitive EOG response in the MOE was attenuated when cAMP
      was increased by odorants or by forskolin suggesting a common mechanism for
      airflow and odorant detection. In addition, the sensitivity to airflow was
      significantly impaired in the MOE from AC3(-/-) mice. We conclude that AC3 in the
      MOE is required for detecting the mechanical force of airflow, which in turn may
      regulate odorant perception during sniffing.

PMID- 23136417
TI  - Aversive stimuli differentially modulate real-time dopamine transmission dynamics
      within the nucleus accumbens core and shell.
AB  - Although fear directs adaptive behavioral responses, how aversive cues recruit
      motivational neural circuitry is poorly understood. Specifically, while it is
      known that dopamine (DA) transmission within the nucleus accumbens (NAc) is
      imperative for mediating appetitive motivated behaviors, its role in aversive
      behavior is controversial. It has been proposed that divergent phasic DA
      transmission following aversive events may correspond to segregated mesolimbic
      dopamine pathways; however, this prediction has never been tested. Here, we used
      fast-scan cyclic voltammetry to examine real-time DA transmission within NAc core
      and shell projection systems in response to a fear-evoking cue. In male Sprague
      Dawley rats, we first demonstrate that a fear cue results in decreased DA
      transmission within the NAc core, but increased transmission within the NAc
      shell. We examined whether these changes in DA transmission could be attributed
      to modulation of phasic transmission evoked by cue presentation. We found that
      cue presentation decreased the probability of phasic DA release in the core,
      while the same cue enhanced the amplitude of release events in the NAc shell. We
      further characterized the relationship between freezing and both changes in DA as
      well as local pH. Although we found that both analytes were significantly
      correlated with freezing in the NAc across the session, changes in DA were not
      strictly associated with freezing while basic pH shifts in the core more
      consistently followed behavioral expression. Together, these results provide the
      first real-time neurochemical evidence that aversive cues differentially modulate
      distinct DA projection systems.

PMID- 23136418
TI  - Somatosensory projections to cochlear nucleus are upregulated after unilateral
      deafness.
AB  - The cochlear nucleus (CN) receives innervation from auditory and somatosensory
      structures, which can be identified using vesicular glutamate transporters,
      VGLUT1 and VGLUT2. VGLUT1 is highly expressed in the magnocellular ventral CN
      (VCN), which receives auditory nerve inputs. VGLUT2 is predominantly expressed in
      the granule cell domain (GCD), which receives nonauditory inputs from
      somatosensory nuclei, including spinal trigeminal nucleus (Sp5) and cuneate
      nucleus (Cu). Two weeks after unilateral deafening VGLUT1 is significantly
      decreased in ipsilateral VCN while VGLUT2 is significantly increased in the
      ipsilateral GCD (Zeng et al., 2009), putatively reflecting decreased inputs from
      auditory nerve and increased inputs from nonauditory structures in guinea pigs.
      Here, we wished to determine whether the upregulation of VGLUT2 represents
      increases in the number of somatosensory projections to the CN that are
      maintained for longer periods of time. Thus, we examined concurrent changes in
      VGLUT levels and somatosensory projections in the CN using immunohistochemistry
      combined with anterograde tract tracing three and six weeks following unilateral
      deafening. The data reveal that unilateral deafness leads to increased numbers of
      VGLUT2-colabeled Sp5 and Cu projections to the ventral and dorsal CN. These
      findings suggest that Sp5 and Cu play significant and unique roles in cross-modal
      compensation and that, unlike after shorter term deafness, neurons in the
      magnocellular regions also participate in the compensation. The enhanced
      glutamatergic somatosensory projections to the CN may play a role in neural
      spontaneous hyperactivity associated with tinnitus.

PMID- 23136419
TI  - Long-term stabilization of place cell remapping produced by a fearful experience.
AB  - Fear is an emotional response to danger that is highly conserved throughout
      evolution because it is critical for survival. Accordingly, episodic memory for
      fearful locations is widely studied using contextual fear conditioning, a
      hippocampus-dependent task (Kim and Fanselow, 1992; Phillips and LeDoux, 1992).
      The hippocampus has been implicated in episodic emotional memory and is thought
      to integrate emotional stimuli within a spatial framework. Physiological evidence
      supporting the role of the hippocampus in contextual fear indicates that
      pyramidal cells in this region, which fire in specific locations as an animal
      moves through an environment, shift their preferred firing locations shortly
      after the presentation of an aversive stimulus (Moita et al., 2004). However, the
      long-term physiological mechanisms through which emotional memories are encoded
      by the hippocampus are unknown. Here we show that during and directly after a
      fearful experience, new hippocampal representations are established and persist
      in the long term. We recorded from the same place cells in mouse hippocampal area
      CA1 over several days during predator odor contextual fear conditioning and found
      that a subset of cells changed their preferred firing locations in response to
      the fearful stimulus. Furthermore, the newly formed representations of the
      fearful context stabilized in the long term. Our results demonstrate that place
      cells respond to the presence of an aversive stimulus, modify their firing
      patterns during emotional learning, and stabilize a long-term spatial
      representation in response to a fearful encounter. The persistent nature of these
      representations may contribute to the enduring quality of emotional memories.

PMID- 23136420
TI  - Within-digit functional parcellation of Brodmann areas of the human primary
      somatosensory cortex using functional magnetic resonance imaging at 7 tesla.
AB  - The primary somatosensory cortex (S1) can be subdivided cytoarchitectonically
      into four distinct Brodmann areas (3a, 3b, 1, and 2), but these areas have never
      been successfully delineated in vivo in single human subjects. Here, we
      demonstrate the functional parcellation of four areas of S1 in individual human
      subjects based on high-resolution functional MRI measurements made at 7 T using
      vibrotactile stimulation. By stimulating four sites along the length of the index
      finger, we were able to identify and locate map reversals of the base to tip
      representation of the index finger in S1. We suggest that these reversals
      correspond to the areal borders between the mirrored representations in the four
      Brodmann areas, as predicted from electrophysiology measurements in nonhuman
      primates. In all subjects, maps were highly reproducible across scanning sessions
      and stable over weeks. In four of the six subjects scanned, four, mirrored,
      within-finger somatotopic maps defining the extent of the Brodmann areas could be
      directly observed on the cortical surface. In addition, by using multivariate
      classification analysis, the location of stimulation on the index finger (four
      distinct sites) could be decoded with a mean accuracy of 65% across subjects. Our
      measurements thus show that within-finger topography is present at the millimeter
      scale in the cortex and is highly reproducible. The ability to identify
      functional areas of S1 in vivo in individual subjects will provide a framework
      for investigating more complex aspects of tactile representation in S1.

PMID- 23136421
TI  - Differential gating of thalamocortical signals by reticular nucleus of thalamus
      during locomotion.
AB  - The thalamic reticular nucleus (RE) provides inhibition to the dorsal thalamus,
      and forms a crucial interface between thalamocortical and corticothalamic
      signals. Whereas there has been significant interest in the role of the RE in
      organizing thalamocortical signaling, information on the activity of the RE in
      the awake animal is scant. Here we investigated the activity of neurons within
      the "motor" compartment of the RE in the awake, unrestrained cat during simple
      locomotion on a flat surface and complex locomotion along a horizontal ladder
      that required visual control of stepping. The activity of 88% of neurons in this
      region was modulated during locomotion. Neurons with receptive fields on the
      shoulder were located dorsally in the nucleus and had regular discharges; during
      locomotion they had relatively low activity and modest magnitudes of stride
      related modulation, and their group activity was distributed over the stride. In
      contrast, neurons with receptive fields on the wrist/paw were located more
      ventrally, often discharged sleep-type bursts during locomotion, were very active
      and profoundly modulated, and their group activity was concentrated in the swing
      and end of stance. Seventy-five percent of RE neurons had different activity
      during the two locomotion tasks. We conclude that during locomotion the RE
      differentially gates thalamocortical signals transmitted during different phases
      of the stride, in relation to different parts of the limb, and the type of
      locomotion task.

PMID- 23136422
TI  - High-frequency hippocampal oscillations activated by optogenetic stimulation of
      transplanted human ESC-derived neurons.
AB  - After transplantation, individual stem cell-derived neurons can functionally
      integrate into the host CNS; however, evidence that neurons derived from
      transplanted human embryonic stem cells (hESCs) can drive endogenous neuronal
      network activity in CNS tissue is still lacking. Here, using multielectrode array
      recordings, we report activation of high-frequency oscillations in the beta and
      gamma ranges (10-100 Hz) in the host hippocampal network via targeted optogenetic
      stimulation of transplanted hESC-derived neurons.

PMID- 23136423
TI  - Thalamocortical asynchrony in conditions of spinal cord injury pain in rats.
AB  - Spinal cord injury (SCI) pain is a debilitating chronic condition that is severe
      and unrelenting. Despite decades of extensive research, the neuropathological
      mechanisms responsible for the development of this devastating condition remain
      largely unknown, hindering our ability to develop effective treatments. Because
      several lines of evidence implicate abnormalities of the thalamus and cortex in
      the etiology of SCI pain, we hypothesized that SCI pain results from abnormal
      functional connectivity of brain areas heavily implicated in pain processing. We
      performed a longitudinal study in a rat model of SCI (SCI group, n = 8; sham
      operated group, n = 6) and acquired resting-state functional magnetic resonance
      imaging scans before spinal surgery and 3, 7, 14, and 21 (SCI only) days after
      surgery in the same animals. Functional connectivity was decreased between the
      ventroposterior lateral thalamus (VPL) and primary somatosensory cortex (S1) 7 d
      after SCI. This reduction preceded an increase in connectivity between S1 and
      other cortical areas involved in nociceptive processing. In addition, VPL had
      increased connectivity to contralateral thalamus at 7 and 14 d after injury. The
      temporal pattern of the increase in functional connectivity within the thalamus
      and between cortical areas (particularly S1 and retrosplenial cortex) had a
      striking resemblance to the temporal pattern for the development of a "below
      level" mechanical hypersensitivity in the same animals. Our findings suggest that
      below-level hypersensitivity is associated with functional disconnection
      (asynchrony) between the thalamus and cortical areas involved in nociceptive
      processing.

PMID- 23136424
TI  - The small G protein H-Ras in the mesolimbic system is a molecular gateway to
      alcohol-seeking and excessive drinking behaviors.
AB  - Uncontrolled consumption of alcohol is a hallmark of alcohol abuse disorders;
      however, the central molecular mechanisms underlying excessive alcohol
      consumption are still unclear. Here, we report that the GTP binding protein, H
      Ras in the nucleus accumbens (NAc) plays a key role in neuroadaptations that
      underlie excessive alcohol-drinking behaviors. Specifically, acute (15 min)
      systemic administration of alcohol (2.5 g/kg) leads to the activation of H-Ras in
      the NAc of mice, which is observed even 24 h later. Similarly, rat operant self
      administration of alcohol (20%) also results in the activation of H-Ras in the
      NAc. Using the same procedures, we provide evidence suggesting that the exchange
      factor GRF1 is upstream of H-Ras activation by alcohol. Importantly, we show that
      infection of mice NAc with lentivirus expressing a short hairpin RNA that targets
      the H-Ras gene produces a significant reduction of voluntary consumption of 20%
      alcohol. In contrast, knockdown of H-Ras in the NAc of mice did not alter water,
      quinine, and saccharin intake. Furthermore, using two-bottle choice and operant
      self-administration procedures, we show that inhibiting H-Ras activity by intra
      NAc infusion of the farnesyltransferase inhibitor, FTI-276, produced a robust
      decrease of rats' alcohol drinking; however, sucrose consumption was unaltered.
      Finally, intra-NAc infusion of FTI-276 also resulted in an attenuation of seeking
      for alcohol. Together, these results position H-Ras as a central molecular
      mediator of alcohol's actions within the mesolimbic system and put forward the
      potential value of the enzyme as a novel target to treat alcohol use disorders.

PMID- 23136425
TI  - Ectopic vesicular glutamate release at the optic nerve head and axon loss in
      mouse experimental glaucoma.
AB  - Although clinical and experimental observations indicate that the optic nerve
      head (ONH) is a major site of axon degeneration in glaucoma, the mechanisms by
      which local retinal ganglion cell (RGC) axons are injured and damage spreads
      among axons remain poorly defined. Using a laser-induced ocular hypertension
      (LIOH) mouse model of glaucoma, we found that within 48 h of intraocular pressure
      elevation, RGC axon segments within the ONH exhibited ectopic accumulation and
      colocalization of multiple components of the glutamatergic presynaptic machinery
      including the vesicular glutamate transporter VGLUT2, several synaptic vesicle
      marker proteins, glutamate, the soluble N-ethylmaleimide-sensitive factor
      attachment protein receptor complex and active zone cytomatrix components, as
      well as ultrastructurally identified, synaptophysin-containing vesicles. Ectopic
      vesicle exocytosis and glutamate release were detected in acute preparations of
      the LIOH ONH. Immunolocalization and analysis using the ionotropic receptor
      channel-permeant cation agmatine indicated that ONH axon segments and glia
      expressed glutamate receptors, and these receptors were more active after LIOH
      compared with controls. Pharmacological antagonism of glutamate receptors and
      neuronal activity resulted in increased RGC axon sparing in vivo. Furthermore, in
      vivo RGC-specific genetic disruption of the vesicular glutamate transporter
      VGLUT2 or the obligatory NMDA receptor subunit NR1 promoted axon survival in
      experimental glaucoma. As the inhibition of ectopic glutamate vesicular release
      or glutamate receptivity can independently modify the severity of RGC axon loss,
      synaptic release mechanisms may provide useful therapeutic entry points into
      glaucomatous axon degeneration.

PMID- 23136426
TI  - Two critical and functionally distinct stages of face and body perception.
AB  - Cortical regions that respond preferentially to particular object categories,
      such as faces and bodies, are essential for visual perception of these object
      categories. However, precisely when these regions play a causal role in
      recognition of their preferred categories is unclear. Here we addressed this
      question using transcranial magnetic stimulation (TMS). Across a series of
      experiments, TMS was delivered over the functionally localized right occipital
      face area (rOFA) or right extrastriate body area (rEBA) at different latencies,
      up to 150 ms, after stimulus onset while adult human participants performed
      delayed match-to-sample tasks on face and body stimuli. Results showed that TMS
      disrupted task performance during two temporally distinct time periods after
      stimulus onset, the first at 40/50 ms and the second at 100/110 ms. These two
      time periods exhibited functionally distinct patterns of impairment: TMS
      delivered during the early time period (at 40/50 ms) disrupted task performance
      for both preferred (faces at rOFA and bodies at rEBA) and nonpreferred (bodies at
      rOFA and faces at rEBA) categories. In contrast, TMS delivered during the later
      time period (at 100/110 ms) disrupted task performance for the preferred category
      only of each area (faces at rOFA and bodies at rEBA). These results indicate that
      category-selective cortical regions are critical for two functionally distinct
      stages of visual object recognition: an early, presumably preparatory stage that
      is not category selective occurring almost immediately after stimulus onset,
      followed by a later stage of category-specific perceptual processing.

PMID- 23136427
TI  - Neurodevelopmental role for VGLUT2 in pyramidal neuron plasticity, dendritic
      refinement, and in spatial learning.
AB  - The level and integrity of glutamate transmission during critical periods of
      postnatal development plays an important role in the refinement of pyramidal
      neuron dendritic arbor, synaptic plasticity, and cognition. Presently, it is not
      clear how excitatory transmission via the two predominant isoforms of the
      vesicular glutamate transporter (VGLUT1 and VGLUT2) participate in this process.
      To assess a neurodevelopmental role for VGLUT2 in pyramidal neuron maturation, we
      generated recombinant VGLUT2 knock-out mice and inactivated VGLUT2 throughout
      development using Emx1-Cre(+/+) knock-in mice. We show that VGLUT2 deficiency in
      corticolimbic circuits results in reduced evoked glutamate transmission, release
      probability, and LTD at hippocampal CA3-CA1 synapses during a formative
      developmental period (postnatal days 11-14). In adults, we find a marked
      reduction in the amount of dendritic arbor across the span of the dendritic tree
      of CA1 pyramidal neurons and reduced long-term potentiation and levels of
      synaptic markers spinophilin and VGLUT1. Loss of dendritic arbor is accompanied
      by corresponding reductions in the number of dendritic spines, suggesting
      widespread alterations in synaptic connectivity. Conditional VGLUT2 knock-out
      mice exhibit increased open-field exploratory activity yet impaired spatial
      learning and memory, endophenotypes similar to those of NMDA receptor knock-down
      mice. Remarkably, the impairment in learning can be partially restored by
      selectively increasing NMDA receptor-mediated glutamate transmission in adult
      mice by prolonged treatment with d-serine and a d-amino acid oxidase inhibitor.
      Our data indicate that VGLUT2 expression is pivotal to the proper development of
      mature pyramidal neuronal architecture and plasticity, and that such
      glutamatergic deficiency leads to cognitive malfunction as observed in several
      neurodevelopmental psychiatric disorders.

PMID- 23136428
TI  - Differential sulfation remodelling of heparan sulfate by extracellular 6-O
      sulfatases regulates fibroblast growth factor-induced boundary formation by glial
      cells: implications for glial cell transplantation.
AB  - Previously, it has been shown that rat Schwann cells (SCs), but not olfactory
      ensheathing cells (OECs), form a boundary with astrocytes, due to a SC-specific
      secreted factor. Here, we identify highly sulfated heparan sulfates (HSs) and
      fibroblast growth factors (FGFs) 1 and 9 as possible determinants of boundary
      formation induced by rat SCs. Disaccharide analysis of HS in SC-conditioned and
      rat OEC-conditioned media showed that SCs secrete more highly sulfated HS than
      OECs. The dependence of the boundary-forming activity on high levels of sulfation
      was confirmed using a panel of semisynthetic modified heparins with variable
      levels of sulfation. Furthermore, extracellular HS 6-O-endosulfatase enzymes,
      Sulf 1 and Sulf 2, were expressed at a significantly lower level by SCs compared
      with OECs, and siRNA reduction of Sulfs in OECs was, in itself, sufficient to
      induce boundary formation. This demonstrates a key role for remodelling
      (reduction) of HS 6-O-sulfation by OECs, compared with SCs, to suppress boundary
      formation. Furthermore, specific anti-FGF1 and anti-FGF9 antibodies disrupted SC
      astrocyte boundary formation, supporting a role for an HS sulfation-dependent FGF
      signaling mechanism via FGF receptors on astrocytes. We propose a model in which
      FGF1 and FGF9 signaling is differentially modulated by patterns of glial cell HS
      sulfation, dependent on Sulf 1 and Sulf 2 expression, to control FGF receptor 3
      IIIb-mediated astrocytic responses. Moreover, these data suggest manipulation of
      HS sulfation after CNS injury as a potential novel approach for therapeutic
      intervention in CNS repair.

PMID- 23136429
TI  - Neurochemical characterization and sexual dimorphism of projections from the
      brain to abdominal and subcutaneous white adipose tissue in the rat.
AB  - Retroperitoneal white adipose tissue (rWAT) and subcutaneous (inguinal) white
      adipose tissue (iWAT) are both innervated and regulated by sympathetic efferents,
      but the distribution and identity of the cells in the brain that regulate
      sympathetic outflow are poorly characterized. Our aim was to use two isogenic
      strains of a neurotropic virus (pseudorabies, Bartha) tagged with either green or
      red fluorescent reporters to identify cells in the brain that project to rWAT
      and/or iWAT. These viruses were injected into separate WAT depots in male and
      female Sprague Dawley rats. Retrogradely labeled neurons in the CNS were
      characterized by immunohistochemistry and PCR. For the latter, laser capture of
      individual virally labeled neurons was used. All virally labeled brain regions
      contained neurons projecting to either and both WAT depots. Neurons to abdominal
      fat were the most abundant in males, whereas females contained a greater
      proportion of neurons to subcutaneous via private lines and collateral branches.
      Retrogradely labeled neurons directed to WAT expressed estrogen receptor-alpha
      (ERalpha), and fewer neurons to subcutaneous WAT expressed ERalpha in males.
      Regardless of sex, projections from the arcuate nucleus were predominantly from
      pro-opiomelanocortin cells, with a notable lack of projections from agouti
      related protein-expressing neurons. Within the lateral hypothalamus, neurons
      directed to rWAT and iWAT expressed orexin and melanin-concentrating hormone
      (MCH), but male rats had a predominance of MCH directed to iWAT. In conclusion,
      the neurochemical substrates that project through polysynaptic pathways to iWAT
      and rWAT are different in male and female rats, suggesting that metabolic
      regulation of rWAT and iWAT is sexually dimorphic.

PMID- 23136430
TI  - A strong constraint to the joint processing of pairs of cortical signals.
AB  - An important question in neuroscience is how the activity from spatially
      distributed cortical representations is integrated and processed together. In
      this study, we used a new approach to investigate the integration of distributed
      cortical activity. We used microstimulation to directly activate pairs of sites
      in primary visual cortex of rhesus monkeys. The sites were activated either
      singly or jointly, and the monkeys were trained to behaviorally report detection
      of the activation of either cortical site. We compared the detection performance
      with predictions from two different mathematical models of signal combination.
      Our data show that, at cortical separations <1 mm, signal integration is well
      described as a linear combination (d' summation) of individual site activity. At
      larger separations, signal integration is better described as a maximum operation
      on the site signals. We compare our neurophysiological findings to existing
      psychophysical data and suggest the intriguing possibility that cortical activity
      originating at spatial separations greater than ~1 mm is processed as if by
      parallel, independent circuits whose signals can be compared against each other
      but not summed. This in turn implies that there is a strong constraint to the
      kinds of computations the brain can perform with spatially distributed cortical
      activity.

PMID- 23136431
TI  - BMP4 sufficiency to induce choroid plexus epithelial fate from embryonic stem
      cell-derived neuroepithelial progenitors.
AB  - Choroid plexus epithelial cells (CPECs) have essential developmental and
      homeostatic roles related to the CSF and blood-CSF barrier they produce.
      Accordingly, CPEC dysfunction has been implicated in many neurological disorders,
      such as Alzheimer's disease, and transplant studies have provided proof-of
      concept for CPEC-based therapies. However, such therapies have been hindered by
      the inability to expand or generate CPECs in culture. During development, CPECs
      differentiate from preneurogenic neuroepithelial cells and require bone
      morphogenetic protein (BMP) signaling, but whether BMPs suffice for CPEC
      induction is unknown. Here we provide evidence for BMP4 sufficiency to induce
      CPEC fate from neural progenitors derived from mouse embryonic stem cells (ESCs).
      CPEC specification by BMP4 was restricted to an early time period after neural
      induction in culture, with peak CPEC competency correlating to neuroepithelial
      cells rather than radial glia. In addition to molecular, cellular, and
      ultrastructural criteria, derived CPECs (dCPECs) had functions that were
      indistinguishable from primary CPECs, including self-assembly into secretory
      vesicles and integration into endogenous choroid plexus epithelium following
      intraventricular injection. We then used BMP4 to generate dCPECs from human ESC
      derived neuroepithelial cells. These findings demonstrate BMP4 sufficiency to
      instruct CPEC fate, expand the repertoire of stem cell-derived neural derivatives
      in culture, and herald dCPEC-based therapeutic applications aimed at the unique
      interface between blood, CSF, and brain governed by CPECs.

PMID- 23136432
TI  - Differential feedback modulation of center and surround mechanisms in
      parvocellular cells in the visual thalamus.
AB  - Many cells in both the central visual system and other sensory systems exhibit a
      center surround organization in their receptive field, where the response to a
      centrally placed stimulus is modified when a surrounding area is also stimulated.
      This can follow from laterally directed connections in the local circuit at the
      level of the cell in question but could also involve more complex interactions.
      In the lateral geniculate nucleus (LGN), the cells relaying the retinal input
      display a concentric, center surround organization that in part follows from the
      similar organization characterizing the retinal cells providing their input.
      However, local thalamic inhibitory interneurons also play a role, and as we
      examine here, feedback from the visual cortex too. Here, we show in the primate
      (macaque) that spatially organized cortical feedback provides a clear and
      differential influence serving to enhance both responses to stimulation within
      the center of the receptive field and the ability of the nonclassical surround
      mechanism to attenuate this. In short, both center and surround mechanisms are
      influenced by the feedback. This dynamically sharpens the spatial focus of the
      receptive field and introduces nonlinearities from the cortical mechanism into
      the LGN.

PMID- 23136433
TI  - Dynamic and static facial expressions decoded from motion-sensitive areas in the
      macaque monkey.
AB  - Humans adeptly use visual motion to recognize socially relevant facial
      information. The macaque provides a model visual system for studying neural
      coding of expression movements, as its superior temporal sulcus (STS) possesses
      brain areas selective for faces and areas sensitive to visual motion. We used
      functional magnetic resonance imaging and facial stimuli to localize motion
      sensitive areas [motion in faces (Mf) areas], which responded more to dynamic
      faces compared with static faces, and face-selective areas, which responded
      selectively to faces compared with objects and places. Using multivariate
      analysis, we found that information about both dynamic and static facial
      expressions could be robustly decoded from Mf areas. By contrast, face-selective
      areas exhibited relatively less facial expression information. Classifiers
      trained with expressions from one motion type (dynamic or static) showed poor
      generalization to the other motion type, suggesting that Mf areas employ separate
      and nonconfusable neural codes for dynamic and static presentations of the same
      expressions. We also show that some of the motion sensitivity elicited by facial
      stimuli was not specific to faces but could also be elicited by moving dots,
      particularly in fundus of the superior temporal and middle superior temporal
      polysensory/lower superior temporal areas, confirming their already well
      established low-level motion sensitivity. A different pattern was found in
      anterior STS, which responded more to dynamic than to static faces but was not
      sensitive to dot motion. Overall, we show that emotional expressions are mostly
      represented outside of face-selective cortex, in areas sensitive to motion. These
      regions may play a fundamental role in enhancing recognition of facial expression
      despite the complex stimulus changes associated with motion.

PMID- 23136434
TI  - Differential reward coding in the subdivisions of the primate caudate during an
      oculomotor task.
AB  - The basal ganglia play a pivotal role in reward-oriented behavior. The striatum,
      an input channel of the basal ganglia, is composed of subdivisions that are
      topographically connected with different cortical and subcortical areas. To test
      whether reward information is differentially processed in the different parts of
      the striatum, we compared reward-related neuronal activity along the dorsolateral
      ventromedial axis in the caudate nucleus of monkeys performing an asymmetrically
      rewarded oculomotor task. In a given block, a target in one position was
      associated with a large reward, whereas the other target was associated with a
      small reward. The target position-reward value contingency was switched between
      blocks. We found the following: (1) activity that reflected the block-wise reward
      contingency emerged before the appearance of a visual target, and it was more
      prevalent in the dorsal, rather than central and ventral, caudate; (2) activity
      that was positively related to the reward size of the current trial was evident,
      especially after reward delivery, and it was more prevalent in the ventral and
      central, rather than dorsal, caudate; and (3) activity that was modulated by the
      memory of the outcomes of the previous trials was evident in the dorsal and
      central caudate. This multiple reward information, together with the target
      direction information, was represented primarily by individual caudate neurons,
      and the different reward information was represented in caudate subpopulations
      with distinct electrophysiological properties, e.g., baseline firing and spike
      width. These results suggest parallel processing of different reward information
      by the basal ganglia subdivisions defined by extrinsic connections and intrinsic
      properties.

PMID- 23136435
TI  - Membrane-proximal tryptophans of synaptobrevin II stabilize priming of secretory
      vesicles.
AB  - Trans-soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP)
      receptor (SNARE) complexes formed between the SNARE motifs of synaptobrevin II,
      SNAP-25, and syntaxin play an essential role in Ca(2+)-regulated exocytosis.
      Apart from the well studied interactions of the SNARE domains, little is known
      about the functional relevance of other evolutionarily conserved structures in
      the SNARE proteins. Here, we show that substitution of two highly conserved
      tryptophan residues within the juxtamembrane domain (JMD) of the vesicular SNARE
      Synaptobrevin II (SybII) profoundly impairs priming of granules in mouse
      chromaffin cells without altering catecholamine release from single vesicles.
      Using molecular dynamic simulations of membrane-embedded SybII, we show that Trp
      residues of the JMD influence the electrostatic surface potential by controlling
      the position of neighboring lysine and arginine residues at the membrane-water
      interface. Our observations indicate a decisive role of the tryptophan moiety of
      SybII in keeping the vesicles in the release-ready state and support a model
      wherein tryptophan-mediated protein-lipid interactions assist in bridging the
      apposing membranes before fusion.

PMID- 23136436
TI  - Modulation of mouse rod response decay by rhodopsin kinase and recoverin.
AB  - Light isomerizes 11-cis-retinal in a retinal rod and produces an active form of
      rhodopsin (Rh*) that binds to the G-protein transducin and activates the
      phototransduction cascade. Rh* is turned off by phosphorylation by rhodopsin
      kinase [G-protein-coupled receptor kinase 1 (GRK1)] and subsequent binding of
      arrestin. To evaluate the role of GRK1 in rod light response decay, we have
      generated the transgenic mouse RKS561L in which GRK1, which is normally present
      at only 2-3% of rhodopsin, is overexpressed by ~12-fold. Overexpression of GRK1
      increases the rate of Rh* phosphorylation and reduces the exponential decay
      constant of the response (tau(REC)) and the limiting time constant (tau(D)) both
      by ~30%; these decreases are highly significant. Similar decreases are produced
      in Rv(-/-) rods, in which the GRK1-binding protein recoverin has been genetically
      deleted. These changes in response decay are produced by acceleration of light
      activated phosphodiesterase (PDE*) decay rather than Rh* decay, because light
      activated PDE* decay remains rate limiting for response decay in both RKS561L and
      Rv(-/-) rods. A model incorporating an effect of GRK1 on light-activated PDE*
      decay rate can satisfactorily account for the changes in response amplitude and
      waveform. Modulation of response decay in background light is nearly eliminated
      by deletion of recoverin. Our experiments indicate that rhodopsin kinase and
      recoverin, in addition to their well-known role in regulating the turning off of
      Rh*, can also modulate the decay of light-activated PDE*, and the effects of
      these proteins on light-activated PDE* decay may be responsible for the
      quickening of response recovery in background light.

PMID- 23136437
TI  - Short-term synaptic plasticity compensates for variability in number of motor
      neurons at a neuromuscular junction.
AB  - We studied how similar postsynaptic responses are maintained in the face of
      interindividual variability in the number of presynaptic neurons. In the
      stomatogastric ganglion of the lobster, Homarus americanus, the pyloric (PY)
      neurons exist in variable numbers across animals. We show that each individual
      fiber of the stomach muscles innervated by PY neurons received synaptic input
      from all neurons present. We performed intracellular recordings of excitatory
      junction potentials (EJPs) in the muscle fibers to determine the consequences of
      differences in the number of motor neurons. Despite the variability in neuron
      number, the compound electrical response of muscle fibers to natural bursting
      input was similar across individuals. The similarity of total synaptic activation
      was not due to differences in the spiking activity of individual motor neurons
      across animals with different numbers of PY neurons. The amplitude of a unitary
      EJP in response to a single spike in a single motor neuron also did not depend on
      the number of PY neurons present. Consequently, the compound EJP in response to a
      single stimulus that activated all motor axons present was larger in individuals
      with more PY neurons. However, when axons were stimulated with trains of pulses
      mimicking bursting activity, EJPs facilitated more in individuals with fewer PY
      neurons. After a few stimuli, this resulted in depolarizations similar to the
      ones in individuals with more PY neurons. We interpret our findings as evidence
      that compensatory or homeostatic regulatory mechanisms can act on short-term
      synaptic dynamics instead of absolute synaptic strength.

PMID- 23136438
TI  - Drosophila neuroligin 2 is required presynaptically and postsynaptically for
      proper synaptic differentiation and synaptic transmission.
AB  - Trans-synaptic adhesion between Neurexins (Nrxs) and Neuroligins (Nlgs) is
      thought to be required for proper synapse organization and modulation, and
      mutations in several human Nlgs have shown association with autism spectrum
      disorders. Here we report the generation and phenotypic characterization of
      Drosophila neuroligin 2 (dnlg2) mutants. Loss of dnlg2 results in reduced bouton
      numbers, aberrant presynaptic and postsynaptic development at neuromuscular
      junctions (NMJs), and impaired synaptic transmission. In dnlg2 mutants, the
      evoked responses are decreased in amplitude, whereas the total active zone (AZ)
      numbers at the NMJ are comparable to wild type, suggesting a decrease in the
      release probability. Ultrastructurally, the presynaptic AZ number per bouton area
      and the postsynaptic density area are both increased in dnlg2 mutants, whereas
      the subsynaptic reticulum is reduced in volume. We show that both presynaptic and
      postsynaptic expression of Dnlg2 is required to restore synaptic growth and
      function in dnlg2 mutants. Postsynaptic expression of Dnlg2 in dnlg2 mutants and
      wild type leads to reduced bouton growth whereas presynaptic and postsynaptic
      overexpression in wild-type animals results in synaptic overgrowth. Since Nlgs
      have been shown to bind to Nrxs, we created double mutants. These mutants are
      viable and display phenotypes that closely resemble those of dnlg2 and dnrx
      single mutants. Our results provide compelling evidence that Dnlg2 functions both
      presynaptically and postsynaptically together with Neurexin to determine the
      proper number of boutons as well as the number of AZs and size of synaptic
      densities during the development of NMJs.

PMID- 23136439
TI  - Inactivating anterior insular cortex reduces risk taking.
AB  - We often have to make risky decisions between alternatives with outcomes that can
      be better or worse than the outcomes of safer alternatives. Although previous
      studies have implicated various brain regions in risky decision making, it
      remains unknown which regions are crucial for balancing whether to take a risk or
      play it safe. Here, we focused on the anterior insular cortex (AIC), the causal
      involvement of which in risky decision making is still unclear, although human
      imaging studies have reported AIC activation in various gambling tasks. We
      investigated the effects of temporarily inactivating the AIC on rats' risk
      preference in two types of gambling tasks, one in which risk arose in reward
      amount and one in which it arose in reward delay. As a control within the same
      subjects, we inactivated the adjacent orbitofrontal cortex (OFC), which is well
      known to affect risk preference. In both gambling tasks, AIC inactivation
      decreased risk preference whereas OFC inactivation increased it. In risk-free
      control situations, AIC and OFC inactivations did not affect decision making.
      These results suggest that the AIC is causally involved in risky decision making
      and promotes risk taking. The AIC and OFC may be crucial for the opposing motives
      of whether to take a risk or avoid it.

PMID- 23136440
TI  - Attention influences single unit and local field potential response latencies in
      visual cortical area V4.
AB  - Many previous studies have demonstrated that changes in selective attention can
      alter the response magnitude of visual cortical neurons, but there has been
      little evidence for attention affecting response latency. Small latency
      differences, though hard to detect, can potentially be of functional importance,
      and may also give insight into the mechanisms of neuronal computation. We
      therefore reexamined the effect of attention on the response latency of both
      single units and the local field potential (LFP) in primate visual cortical area
      V4. We find that attention does produce small (1-2 ms) but significant reductions
      in the latency of both the spiking and LFP responses. Though attention, like
      contrast elevation, reduces response latencies, we find that the two have
      different effects on the magnitude of the LFP. Contrast elevations increase and
      attention decreases the magnitude of the initial deflection of the stimulus
      evoked LFP. Both contrast elevation and attention increase the magnitude of the
      spiking response. We speculate that latencies may be reduced at higher contrast
      because stronger stimulus inputs drive neurons more rapidly to spiking threshold,
      while attention may reduce latencies by placing neurons in a more depolarized
      state closer to threshold before stimulus onset.

PMID- 23136441
TI  - Long-term changes in trigeminal ganglionic and thalamic neuronal activities
      following inferior alveolar nerve transection in behaving rats.
AB  - The transection of the inferior alveolar nerve (IANx) produces allodynia in the
      whisker pad (V2 division) of rats. Ectopic discharges from injured trigeminal
      ganglion (TG) neurons and thalamocortical reorganization are possible
      contributors to the sensitization of uninjured V2 primary and CNS neurons. To
      test which factor is more important, TG and ventroposterior medial nucleus (VPM)
      neurons were longitudinally followed before, during, and after IANx for up to 80
      d. Spontaneous discharges and mechanical stimulation-evoked responses were
      recorded in conscious and in anesthetized states. Results show (1) a sequential
      increase in spontaneous activities, first in the injured TG neurons of the IAN (2
      30 d), followed by uninjured V2 ganglion neurons (6-30 d), and then VPM V2
      neurons (7-30 d) after IANx; (2) ectopic discharges included burst and regular
      firing patterns in the IAN and V2 branches of the TG neurons; and (3) the
      receptive field expanded, the modality shifted, and long-lasting after-discharges
      occurred only in VPM V2 neurons. All of these changes appeared in the late or
      maintenance phase (7-30 d) and disappeared during the recovery phase (40-60 d).
      These observations suggest that ectopic barrages in the injured IAN contribute
      more to the development of sensitization, whereas the modality shift and evoked
      after-discharges in the VPM thalamic neurons contribute more to the maintenance
      phase of allodynia by redirecting tactile information to the cortex as
      nociceptive.

PMID- 23136442
TI  - Neural synchronization during face-to-face communication.
AB  - Although the human brain may have evolutionarily adapted to face-to-face
      communication, other modes of communication, e.g., telephone and e-mail,
      increasingly dominate our modern daily life. This study examined the neural
      difference between face-to-face communication and other types of communication by
      simultaneously measuring two brains using a hyperscanning approach. The results
      showed a significant increase in the neural synchronization in the left inferior
      frontal cortex during a face-to-face dialog between partners but none during a
      back-to-back dialog, a face-to-face monologue, or a back-to-back monologue.
      Moreover, the neural synchronization between partners during the face-to-face
      dialog resulted primarily from the direct interactions between the partners,
      including multimodal sensory information integration and turn-taking behavior.
      The communicating behavior during the face-to-face dialog could be predicted
      accurately based on the neural synchronization level. These results suggest that
      face-to-face communication, particularly dialog, has special neural features that
      other types of communication do not have and that the neural synchronization
      between partners may underlie successful face-to-face communication.

PMID- 23136443
TI  - Left ventricular mass as a discriminator of left atrial appendage thrombus in
      persistent atrial fibrillation: promise or over-enthusiasm?

PMID- 23136444
TI  - Response to the letter: "Left ventricular mass as a discriminator of left atrial
      appendage thrombus in persistent atrial fibrillation: promise or over
      enthusiasm?".

PMID- 23136445
TI  - Appropriate criteria for the use of cardiac computed tomography angiography.

PMID- 23136446
TI  - Haemodynamic response during low-dose dobutamine infusion in patients with
      chronic systolic heart failure: comparison of echocardiographic and invasive
      measurements.
AB  - AIMS: To investigate whether left ventricular (LV) systolic shortening velocity
      (s'), diastolic lengthening velocity (e'), and non-invasively estimated LV
      filling pressure (E/e') during low-dose dobutamine echocardiography (LDDE)
      reflect invasive measures of cardiac output and pulmonary capillary wedge
      pressure (PCWP) in stable patients with chronic systolic heart failure. METHODS
      AND RESULTS: Fourteen patients with heart failure (aged 65 +/- 8 years, LVEF 36
      +/- 8%) underwent simultaneous tissue Doppler echocardiography and invasive
      measurements of cardiac output and PCWP by right heart catheterization at rest
      and during dobutamine infusion at rates of 10 and 20 ug/kg/min. Cardiac output
      increased from rest to peak dobutamine (4.9 +/- 1.2 to 6.6 +/- 2.0 L/min, P <
      0.001) and correlated with the peak systolic tissue velocity (s') at rest (R =
      0.61, P = 0.02) and during dobutamine stimulation (R = 0.79, P < 0.001).
      Increases in early diastolic mitral inflow (E, 74.9 +/- 29.0-90.8 +/- 29.5 cm/s)
      and LV lengthening (e', 6.5 +/- 2.4-8.2 +/- 2.8 cm/s) velocities were observed
      during LDDE leaving the E/e' ratio unchanged. Although a mean PCWP was also
      unchanged from rest to peak dobutamine (16.6 +/- 8.3-14.2 +/- 9.2, P = 0.25),
      E/e' and PCWP only correlated at rest (R = 0.64, P = 0.014). CONCLUSION: The LV
      systolic shortening velocity is closely associated with cardiac output during
      LDDE in CHF patients. Dobutamine stimulation increases early diastolic mitral
      inflow and lengthening velocities, but the E/e' ratio does not reflect the PCWP
      during LDDE, which warrants some caution in converting changes in E/e' into
      changes in LV filling pressure. The sample size is, however, small and the
      observation need to be confirmed in a larger population.

PMID- 23136447
TI  - Race and Ethnic Differences in College Achievement: Does High School Attended
      Matter?
AB  - This paper uses 10 years of enrollment data at four Texas public universities to
      examine whether, to what extent, and in what ways high school attended
      contributes to racial and ethnic differences in college achievement. Like
      previous studies, we show that controlling for observable pre-college achievement
      variables (e.g. test scores, class rank) shrinks, but does not eliminate, sizable
      racial differences in college achievement. Fixed-effects models that take into
      account differences across high schools that minority and nonminority youth
      attend largely eliminate, and often reverse, black-white and Hispanic-white gaps
      in several measures of college achievement. Our results, which are quite robust
      across universities of varying selectivity, illustrate how high school quality
      foments race and ethnic inequality in postsecondary achievement. Leveling
      inequities in the quality of high schools that minority students attend is a long
      run agenda, but remediation programs that compensate for instructional shortfalls
      at low performing high schools may help close achievement gaps in the interim.

PMID- 23136448
TI  - Solvation Structure and Energetics of Single Ions at the Aqueous Liquid-Vapor
      Interface.
AB  - Potentials of mean force for single, nonpolarizable monovalent halide anions and
      alkali cations are computed for transversing the water-air interface (modeling
      using polarizable TIP4P-FQ and TIP4P-QDP). Iodide and bromide in TIP4P-FQ show
      interfacial stability, whereas chloride, bromide, and iodide show interfacial
      stability in TIP4P-QDP. A monotonic decrease in coordination number and an
      increasingly anisotropic distribution of solvating water molecules is shown to
      accompany movement of the ions towards vapor conditions; these effects are most
      noticeable with increases in ion size/decreases in magnitude of hydration free
      energy.

PMID- 23136449
TI  - Parental Strains and Rewards among Mothers: The Role of Education.
AB  - Using data from the NICHD Study of Early Child Care and Youth Development (N =
      1,198), this study examines the associations between education and parental
      strains and rewards among mothers of young children. Findings indicate that a
      college degree or more is related to less parenting anxiety, but more role
      captivity, and less new life meaning from parenting than lower levels of
      education. Differences by education are partly explained by variation in levels
      of progressive parenting values and work commitment, but remain significant.
      These patterns indicate that education provides greater resources that ease
      parental anxiety, but also leads to greater perceived demands of having a
      successful career, which contribute to more role captivity and less new life
      meaning from parenting.

PMID- 23136450
TI  - Where Our Number Concepts Come From.

PMID- 23136451
TI  - Biomimetic Synthesis of Cbz-(S)-Dolaphenine.
AB  - A new route to Cbz-(S)-dolaphenine, a recurring element in bioactive peptidic
      natural products, has been implemented, which closely parallels the biogenetic
      pathway. Cyclodehydration of 11 to yield thiazoline 2 allows for a Ni(0)-promoted
      decarbonylative aromatization to provide the thiazole framework with retention of
      stereochemistry.

PMID- 23136452
TI  - Evaluation of the Impacts of Marine Salts and Asian Dust on the Forested
      Yakushima Island Ecosystem, a World Natural Heritage Site in Japan.
AB  - To elucidate the influence of airborne materials on the ecosystem of Japan's
      Yakushima Island, we determined the elemental compositions and Sr and Nd isotope
      ratios in streamwater, soils, vegetation, and rocks. Streamwater had high Na and
      Cl contents, low Ca and HCO(3) contents, and Na/Cl and Mg/Cl ratios close to
      those of seawater, but it had low pH (5.4 to 7.1), a higher Ca/Cl ratio than
      seawater, and distinct (87)Sr/(86)Sr ratios that depended on the bedrock type.
      The proportions of rain-derived cations in streamwater, estimated by assuming
      that Cl was derived from sea salt aerosols, averaged 81 % for Na, 83 % for Mg, 36
      % for K, 32 % for Ca, and 33 % for Sr. The Sr value was comparable to the 28 %
      estimated by comparing Sr isotope ratios between rain and granite bedrock. The
      soils are depleted in Ca, Na, P, and Sr compared with the parent materials. At
      Yotsuse in the northwestern side, plants and the soil pool have (87)Sr/(86)Sr
      ratios similar to that of rainwater with a high sea salt component. In contrast,
      the Sr and Nd isotope ratios of soil minerals in the A and B horizons approach
      those of silicate minerals in northern China's loess soils. The soil Ca and P
      depletion results largely from chemical weathering of plagioclase and of small
      amounts of apatite and calcite in granitic rocks. This suggests that Yakushima's
      ecosystem is affected by large amounts of acidic precipitation with a high sea
      salt component, which leaches Ca and its proxy (Sr) from bedrock into streams,
      and by Asian dust-derived apatite, which is an important source of P in base
      cation-depleted soils.

PMID- 23136453
TI  - Chemometric Study of the Ex Situ Underground Coal Gasification Wastewater
      Experimental Data.
AB  - The main goal of the study was the analysis of the parameters of wastewater
      generated during the ex situ underground coal gasification (UCG) experiments on
      lignite from Belchatow, and hard coal from Ziemowit and Bobrek coal mines,
      simulated in the ex situ reactor. The UCG wastewater may pose a potential threat
      to the groundwater since it contains high concentrations of inorganic (i.e.,
      ammonia nitrogen, nitrites, chlorides, free and bound cyanides, sulfates and
      trace elements: As, B, Cr, Zn, Al, Cd, Co, Mn, Cu, Mo, Ni, Pb, Hg, Se, Ti, Fe)
      and organic (i.e., phenolics, benzene and their alkyl derivatives, and polycyclic
      aromatic hydrocarbons) contaminants. The principal component analysis and
      hierarchical clustering analysis enabled to effectively explore the similarities
      and dissimilarities between the samples generated in lignite and hard coal oxygen
      gasification process in terms of the amounts and concentrations of particular
      components. The total amount of wastewater produced in lignite gasification
      process was higher than the amount generated in hard coal gasification
      experiments. The lignite gasification wastewater was also characterized by the
      highest contents of acenaphthene, phenanthrene, anthracene, fluoranthene, and
      pyrene, whereas hard coal gasification wastewater was characterized by relatively
      higher concentrations of nitrites, As, Cr, Cu, benzene, toluene, xylene,
      benzo(a)anthracene, chrysene, benzo(b)fluoranthene, benzo(k)fluoranthene, and
      benzo(a)pyrene.

PMID- 23136454
TI  - Influence of Thermally Polluted Water on the Growth of Helophytes in the Vicinity
      of a Colliery Waste Tip.
AB  - The impact of thermal pollution of leachate from a post-coal mine heap on three
      macrophyte species: Phragmites australis, Typha latifolia, and Scirpus sylvaticus
      was examined over the entire vegetation season. Hydrological measurements showed
      that the temperature of the leachate was ca 50  degrees C at the site of leachate
      inflow and decreased to ca 15  degrees C at the end of discharge canal. The
      annual temperature and conductivity of leachate from the two control sites, a
      polluted water stream in the vicinity of the waste tip and an unpolluted stream,
      differ significantly. However, only the temperature explained the differences in
      plant traits. In April, and in some cases in May, plants in the leachate were
      significantly higher than in those on the control sites in terms of biomass and
      plant height. Thermal pollution caused a phenological shift in all species and
      also caused Scirpus plants to die out more quickly. Temperature also affected the
      proportion flowering vs. vegetative individuals, e.g., none of Scirpus plants
      started to bloom.

PMID- 23136455
TI  - Winners and Losers: Changes in Texas University Admissions post-Hopwood.
AB  - This paper evaluates changes in the racial and ethnic composition of admissions
      at three Texas universities following the judicial ban on affirmative action
      imposed by the 1996 Hopwood decision. We estimate the extent to which
      universities practiced affirmative action before the judicial ban, and evaluate
      how admission officers at these universities changed the relative weights
      accorded to various applicant characteristics during the ban. After assessing
      whether changes in the relative weights favored minority applicants, we simulate
      the degree to which these new policies succeeded in maintaining minority
      admission rates at their pre-Hopwood levels. We find that these universities
      complied with the Hopwood ruling such that direct advantages given to black and
      Hispanic applicants disappeared (and, in some cases, became disadvantages). While
      we find some evidence that universities changed the weights they placed on
      applicant characteristics aside from race and ethnicity in ways that aided
      underrepresented minority applicants, these changes in the admissions process
      were insufficient to fully restore black and Hispanic applicants' share of
      admitted students.

PMID- 23136456
TI  - College Graduation Rates for Minority Students in a Selective Technical
      University: Will Participation in a Summer Bridge Program Contribute to Success?
AB  - There are many approaches to solving the problem of underrepresentation of some
      racial and ethnic groups and women in scientific and technical disciplines. Here,
      the authors evaluate the association of a summer bridge program with the
      graduation rate of underrepresented minority (URM) students at a selective
      technical university. They demonstrate that this 5-week program prior to the fall
      of the 1st year contains elements reported as vital for successful student
      retention. Using multivariable survival analysis, they show that for URM students
      entering as fall-semester freshmen, relative to their nonparticipating peers,
      participation in this accelerated summer bridge program is associated with higher
      likelihood of graduation. The longitudinal panel data include more than 2,200 URM
      students.

PMID- 23136457
TI  - The Colletotrichum boninense species complex.
AB  - Although only recently described, Colletotrichum boninense is well established in
      literature as an anthracnose pathogen or endophyte of a diverse range of host
      plants worldwide. It is especially prominent on members of Amaryllidaceae,
      Orchidaceae, Proteaceae and Solanaceae. Reports from literature and preliminary
      studies using ITS sequence data indicated that C. boninense represents a species
      complex. A multilocus molecular phylogenetic analysis (ITS, ACT, TUB2, CHS-1,
      GAPDH, HIS3, CAL) of 86 strains previously identified as C. boninense and other
      related strains revealed 18 clades. These clades are recognised here as separate
      species, including C. boninense s. str., C. hippeastri, C. karstii and 12
      previously undescribed species, C. annellatum, C. beeveri, C. brassicicola, C.
      brasiliense, C. colombiense, C. constrictum, C. cymbidiicola, C. dacrycarpi, C.
      novae-zelandiae, C. oncidii, C. parsonsiae and C. torulosum. Seven of the new
      species are only known from New Zealand, perhaps reflecting a sampling bias. The
      new combination C. phyllanthi was made, and C. dracaenae Petch was epitypified
      and the name replaced with C. petchii. Typical for species of the C. boninense
      species complex are the conidiogenous cells with rather prominent periclinal
      thickening that also sometimes extend to form a new conidiogenous locus or
      annellations as well as conidia that have a prominent basal scar. Many species in
      the C. boninense complex form teleomorphs in culture. TAXONOMIC NOVELTIES: New
      combination - Colletotrichum phyllanthi (H. Surendranath Pai) Damm, P.F. Cannon &
      Crous. Name replacement - C. petchii Damm, P.F. Cannon & Crous. New species - C.
      annellatum Damm, P.F. Cannon & Crous, C. beeveri Damm, P.F. Cannon, Crous, P.R.
      Johnst. & B. Weir, C. brassicicola Damm, P.F. Cannon & Crous, C. brasiliense
      Damm, P.F. Cannon, Crous & Massola, C. colombiense Damm, P.F. Cannon, Crous, C.
      constrictum Damm, P.F. Cannon, Crous, P.R. Johnst. & B. Weir, C. cymbidiicola
      Damm, P.F. Cannon, Crous, P.R. Johnst. & B. Weir, C. dacrycarpi Damm, P.F.
      Cannon, Crous, P.R. Johnst. & B. Weir, C. novae-zelandiae Damm, P.F. Cannon,
      Crous, P.R. Johnst. & B. Weir, C. oncidii Damm, P.F. Cannon & Crous, C.
      parsonsiae Damm, P.F. Cannon, Crous, P.R. Johnst. & B. Weir, C. torulosum Damm,
      P.F. Cannon, Crous, P.R. Johnst. & B. Weir. Typifications: Epitypifications - C.
      dracaenae Petch.

PMID- 23136458
TI  - The Colletotrichum acutatum species complex.
AB  - Colletotrichum acutatum is known as an important anthracnose pathogen of a wide
      range of host plants worldwide. Numerous studies have reported subgroups within
      the C. acutatum species complex. Multilocus molecular phylogenetic analysis (ITS,
      ACT, TUB2, CHS-1, GAPDH, HIS3) of 331 strains previously identified as C.
      acutatum and other related taxa, including strains from numerous hosts with wide
      geographic distributions, confirmed the molecular groups previously recognised
      and identified a series of novel taxa. Thirty-one species are accepted, of which
      21 have not previously been recognised. Colletotrichum orchidophilum clusters
      basal to the C. acutatum species complex. There is a high phenotypic diversity
      within this complex, and some of the species appear to have preferences to
      specific hosts or geographical regions. Others appear to be plurivorous and are
      present in multiple regions. In this study, only C. salicis and C. rhombiforme
      formed sexual morphs in culture, although sexual morphs have been described from
      other taxa (especially as laboratory crosses), and there is evidence of
      hybridisation between different species. One species with similar morphology to
      C. acutatum but not belonging to this species complex was also described here as
      new, namely C. pseudoacutatum. TAXONOMIC NOVELTIES: New combinations -
      Colletotrichum limetticola (R.E. Clausen) Damm, P.F. Cannon & Crous, C. lupini
      (Bondar) Damm, P.F. Cannon & Crous, C. salicis (Fuckel) Damm, P.F. Cannon &
      Crous. New species - C. acerbum Damm, P.F. Cannon & Crous, C. australe Damm, P.F.
      Cannon & Crous, C. brisbanense Damm, P.F. Cannon & Crous, C. cosmi Damm, P.F.
      Cannon & Crous, C. costaricense Damm, P.F. Cannon & Crous, C. cuscutae Damm, P.F.
      Cannon & Crous, C. guajavae Damm, P.F. Cannon & Crous, C. indonesiense Damm, P.F.
      Cannon & Crous, C. johnstonii Damm, P.F. Cannon & Crous, C. kinghornii Damm, P.F.
      Cannon & Crous, C. laticiphilum Damm, P.F. Cannon & Crous, C. melonis Damm, P.F.
      Cannon & Crous, C. orchidophilum Damm, P.F. Cannon & Crous, C. paxtonii Damm,
      P.F. Cannon & Crous, C. pseudoacutatum Damm, P.F. Cannon & Crous C. pyricola
      Damm, P.F. Cannon & Crous, C. rhombiforme Damm, P.F. Cannon & Crous, C. scovillei
      Damm, P.F. Cannon & Crous, C. sloanei Damm, P.F. Cannon & Crous, C. tamarilloi
      Damm, P.F. Cannon & Crous, C. walleri Damm, P.F. Cannon & Crous. Typifications:
      Epitypifications - C. acutatum J.H. Simmonds, C. limetticola (R.E. Clausen) Damm,
      P.F. Cannon & Crous, C. nymphaeae (Pass.) Aa, C. phormii (Henn.) D.F. Farr &
      Rossman, C. salicis (Fuckel) Damm, P.F. Cannon & Crous. Lectotypifications - C.
      nymphaeae (Pass.) Aa, C. orchidearum Allesch.

PMID- 23136459
TI  - The Colletotrichum gloeosporioides species complex.
AB  - The limit of the Colletotrichum gloeosporioides species complex is defined
      genetically, based on a strongly supported clade within the Colletotrichum ITS
      gene tree. All taxa accepted within this clade are morphologically more or less
      typical of the broadly defined C. gloeosporioides, as it has been applied in the
      literature for the past 50 years. We accept 22 species plus one subspecies within
      the C. gloeosporioides complex. These include C. asianum, C. cordylinicola, C.
      fructicola, C. gloeosporioides, C. horii, C. kahawae subsp. kahawae, C. musae, C.
      nupharicola, C. psidii, C. siamense, C. theobromicola, C. tropicale, and C.
      xanthorrhoeae, along with the taxa described here as new, C. aenigma, C.
      aeschynomenes, C. alatae, C. alienum, C. aotearoa, C. clidemiae, C. kahawae
      subsp. ciggaro, C. salsolae, and C. ti, plus the nom. nov. C. queenslandicum (for
      C. gloeosporioides var. minus). All of the taxa are defined genetically on the
      basis of multi-gene phylogenies. Brief morphological descriptions are provided
      for species where no modern description is available. Many of the species are
      unable to be reliably distinguished using ITS, the official barcoding gene for
      fungi. Particularly problematic are a set of species genetically close to C.
      musae and another set of species genetically close to C. kahawae, referred to
      here as the Musae clade and the Kahawae clade, respectively. Each clade contains
      several species that are phylogenetically well supported in multi-gene analyses,
      but within the clades branch lengths are short because of the small number of
      phylogenetically informative characters, and in a few cases individual gene trees
      are incongruent. Some single genes or combinations of genes, such as
      glyceraldehyde-3-phosphate dehydrogenase and glutamine synthetase, can be used to
      reliably distinguish most taxa and will need to be developed as secondary
      barcodes for species level identification, which is important because many of
      these fungi are of biosecurity significance. In addition to the accepted species,
      notes are provided for names where a possible close relationship with C.
      gloeosporioides sensu lato has been suggested in the recent literature, along
      with all subspecific taxa and formae speciales within C. gloeosporioides and its
      putative teleomorph Glomerella cingulata. TAXONOMIC NOVELTIES: Name replacement -
      C. queenslandicum B. Weir & P.R. Johnst. New species - C. aenigma B. Weir & P.R.
      Johnst., C. aeschynomenes B. Weir & P.R. Johnst., C. alatae B. Weir & P.R.
      Johnst., C. alienum B. Weir & P.R. Johnst, C. aotearoa B. Weir & P.R. Johnst., C.
      clidemiae B. Weir & P.R. Johnst., C. salsolae B. Weir & P.R. Johnst., C. ti B.
      Weir & P.R. Johnst. New subspecies - C. kahawae subsp. ciggaro B. Weir & P.R.
      Johnst. Typification: Epitypification - C. queenslandicum B. Weir & P.R. Johnst.

PMID- 23136461
TI  - Cohesion, coherence, and declarative memory: Discourse patterns in individuals
      with hippocampal amnesia.
AB  - BACKGROUND: Discourse cohesion and coherence gives our communication continuity.
      Deficits in cohesion and coherence have been reported in patients with cognitive
      communication disorders (e.g., TBI, dementia). However, the diffuse nature of
      pathology and widespread cognitive deficits of these disorders have made
      identification of specific neural substrates and cognitive systems critical for
      cohesion and coherence challenging.  AIMS: Taking advantage of a rare patient
      group with selective and severe declarative memory impairments, the current study
      attempts to isolate the contribution of declarative memory to the successful use
      of cohesion and coherence in discourse.  METHODS #ENTITYSTARTX00026; PROCEDURES:
      Cohesion and coherence were examined in the discourse of six participants with
      hippocampal amnesia and six demographically matched comparison participants.
      Specifically, this study (1) documents the frequency, type, and completeness of
      cohesive ties; (2) evaluates discourse for local and global coherence; and (3)
      compares use of cohesive ties and coherence ratings in amnesia and healthy
      participants.  OUTCOMES #ENTITYSTARTX00026; RESULTS: Overall, amnesia
      participants produced fewer cohesive ties per T-unit, the adequacy of their ties
      were more often judged to be incomplete, and the ratings of their local coherence
      were consistently lower than comparison participants.  CONCLUSIONS: These
      findings suggest that declarative memory may contribute to the discursive use of
      cohesion and coherence. Broader notions of cohesion, or interactional cohesion,
      i.e., cohesion across speakers (two or more people), time (days, weeks), and
      communicative resources (gesture), warrant further study as the experimental
      tasks used in the literature, and here, may actually underestimate or
      overestimate the extent of impairment.

PMID- 23136460
TI  - Colletotrichum - current status and future directions.
AB  - A review is provided of the current state of understanding of Colletotrichum
      systematics, focusing on species-level data and the major clades. The taxonomic
      placement of the genus is discussed, and the evolution of our approach to species
      concepts and anamorph-teleomorph relationships is described. The application of
      multilocus technologies to phylogenetic analysis of Colletotrichum is reviewed,
      and selection of potential genes/loci for barcoding purposes is discussed. Host
      specificity and its relation to speciation and taxonomy is briefly addressed. A
      short review is presented of the current status of classification of the species
      clusters that are currently without comprehensive multilocus analyses,
      emphasising the orbiculare and destructivum aggregates. The future for
      Colletotrichum biology will be reliant on consensus classification and robust
      identification tools. In support of these goals, a Subcommission on
      Colletotrichum has been formed under the auspices of the International Commission
      on Taxonomy of Fungi, which will administer a carefully curated barcode database
      for sequence-based identification of species within the BioloMICS web
      environment.

PMID- 23136462
TI  - Visual Attention to Antismoking PSAs: Smoking Cues Versus Other Attention
      Grabbing Features.
AB  - This study examines how addicted smokers attend visually to smoking-related
      public service announcements (PSAs) in adults smokers. Smokers' onscreen visual
      fixation is an indicator of cognitive resources allocated to visual attention.
      Characteristic of individuals with addictive tendencies, smokers are expected to
      be appetitively activated by images of their addiction-specifically smoking cues.
      At the same time, these cues are embedded in messages that associate avoidance
      responses with these appetitive cues, potentially inducing avoidance of PSA
      processing. Findings suggest that segments of PSAs that contain smoking cues are
      processed similarly to segments that contain complex stimuli (operationalized in
      this case as high in information introduced) and that visual attention is aligned
      with smoking cues on the screen.

PMID- 23136463
TI  - Do Subtle Cues About Belongingness Constrain Women's Career Choices?
AB  - Nilanjana Dasgupta's (this issue) stereotype inoculation model (SIM) helps
      explain why what feels like a free choice to pursue one life path over another
      "is often constrained by subtle cues in achievement environments that signal who
      naturally belongs there and is most likely to succeed and who else is a dubious
      fit" (p. 231). She posits that seeing others like themselves in successful roles
      inoculates women against negative stereotypes that impede their success and
      persistence in specific achievement contexts.As is true of classic theoretical
      positions (see Nagel, 1961), Dasgupta presents postulates from which she deduces
      a specific set of hypotheses, and she reviews the relevant
      empirical/observational data in support of them. It is precisely what this area
      of research has long needed-moving beyond demonstrations of identity threats to a
      theory about their underlying causes, conditions, and interventions. This
      proposal leads her to four broad predictions, the first of which is the primary
      focus of our comment.

PMID- 23136464
TI  - Constructing Home and Family: How the Ballroom Community Supports African
      American GLBTQ Youth in the Face of HIV/AIDS.
AB  - This article focuses on the construction of homes and families within the
      ballroom community, a prominent feature of urban GLBTQ communities of color in
      cities across the United States. Based on two ethnographic studies with ballroom
      communities in the San Francisco Bay Area, California, and Detroit, Michigan, we
      explore the importance of gender and sexual identity in informing community
      practice around HIV prevention and treatment. As a community, the ballroom scene
      provides African American queer youth with support for same-sex desire and
      identity, along with multiple forms of support for HIV prevention. Our study of
      the ballroom community documents current forms of "intravention" occurring within
      the community and the importance of the gender-sex system in organizing these
      practices. We also offer recommendations for community-based organizations to
      partner with the ballroom community, making use of existing social structures
      within the community and the salient concepts of home and family, to provide HIV
      related services and support. We argue for HIV-prevention interventions to take a
      more culturally appropriate, nuanced approach to reaching African American youth
      at risk, utilizing community and family structures, in whatever forms these may
      take.

PMID- 23136465
TI  - The role of electrostatic interactions on klentaq1 insight for domain separation.
AB  - We investigated the relationship between the thermostability of Klentaq1 and
      factors stabilizing interdomain interactions. When thermal adaptation of Klentaq1
      was analyzed at the atomic level, the protein was stable at 300 and 350 K. It
      gradually unfolded at 373 K and almost spontaneously unfolded at 400 K. Domain
      separation was induced by disrupting electrostatic interactions in two salt
      bridges formed by Lys354-Glu445 and Asp371-Arg435 on the interface domain. The
      role of these interactions in protein stability was evaluated by comparing free
      energy solvation (DeltaDeltaG(solv)) between wild type and mutants. Substitution
      of Asp371 by Glu or Asn, and also Glu445 by Asn resulted in a positive value of
      DeltaDeltaG(solv), suggesting that mutations destabilized the protein structure.
      Nevertheless, substitution of Glu445 by Asp gave a negative value to
      DeltaDeltaG(solv) reflecting increasing protein stability. Our results
      demonstrate that interactions at the interface domains of Klentaq1 are essential
      factors correlated with the Klentaq1 thermostability.

PMID- 23136467
TI  - Power of conventional rice breeding.

PMID- 23136466
TI  - Lack of Influence of the Androgen Receptor Gene CAG-Repeat Polymorphism on
      Clinical and Electrocardiographic Manifestations of the Brugada Syndrome in Man.
AB  - BACKGROUND: Clinical studies suggest that testosterone (T) plays an important
      role in the male predominance of the clinical manifestations of the Brugada
      syndrome (BS). However, no statistically significant correlations have been
      observed between T levels and electrocardiogram (ECG) parameters in the BS
      patients. We investigated whether the hormonal pattern and the variation within
      CAG repeat polymorphism in exon 1 of the androgen receptor (AR) gene, affecting
      androgen sensitivity, are associated with the Brugada ECG phenotype in males.
      METHODS AND RESULTS: 16 male patients with BS (mean age 45.06 +/- 11.3 years)
      were studied. 12-lead ECG was recorded. Blood levels of follicle-stimulating
      hormone, luteinizing hormone, prolactin, testosterone, free-T,
      dihydrotestosterone, 17-beta-estradiol, estrone, 3-alpha-androstanediol
      glucuronide, delta-4-androstenedione, dehydroepiandrosterone sulphate,
      progesterone, 17-hydroxyprogesterone, and sex hormone binding globulin were
      assayed. Genotyping of CAG repeats on DNA extracted from leukocytes was carried
      out. No relationship was found between hormone values and ECG parameters of BS.
      BS patients showed the CAG length normally recognized in the human polymorphism
      range and the number of CAG repeats did not correlate with the ECG pattern of BS.
      CONCLUSIONS: The AR CAG repeat length does not correlate with the ECG features of
      the patients affected by BS. The search for genes downstream AR activation as
      possibly responsible for the increased risk of spontaneous arrhythmias in BS
      males after puberty is warranted.

PMID- 23136468
TI  - Overexpression of the pathogen-inducible wheat TaWRKY45 gene confers disease
      resistance to multiple fungi in transgenic wheat plants.
AB  - Recently we cloned and characterized the gene for the wheat transcription factor
      TaWRKY45 and showed that TaWRKY45 was upregulated in response to benzothiadiazole
      (BTH) and Fusarium head blight (FHB) and that its overexpression conferred
      enhanced resistance against F. graminearum. To characterize the functional role
      of TaWRKY45 in the disease resistance of wheat, in the present study we conducted
      expression analyses of TaWRKY45 with inoculations of powdery mildew and leaf rust
      and evaluated TaWRKY45-overexpressing wheat plants for resistance to these
      diseases. TaWRKY45 was upregulated in response to infections with Blumeria
      graminis, a causal fungus for powdery mildew, and Puccinia triticina, a causal
      fungus for leaf rust. Constitutive overexpression of the TaWRKY45 transgene
      conferred enhanced resistance against these two fungi on transgenic wheat plants
      grown under greenhouse conditions. However, the expression of two resistance
      related genes, Pm3 and Lr34, was not induced by the inoculation with powdery
      mildew in TaWRKY45-overexpressing wheat plants. These results suggest that
      TaWRKY45 is involved in the defense responses for multiple fungal diseases in
      wheat but that resistance involving TaWRKY45 differs from at least Pm3 and/or
      Lr34-related resistance. Our present and previous studies indicate that TaWRKY45
      may be potentially utilized to improve a wide range of disease resistance in
      wheat.

PMID- 23136469
TI  - N(2)O induces mitotic polyploidization in anther somatic cells and restores
      fertility in sterile interspecific hybrid lilies.
AB  - Fertile plants undergoing male gametogenesis can be treated with nitrous oxide
      (N(2)O) gas to obtain 2n male gametes. N(2)O treatment is also expected to
      restore the fertility of interspecific hybrids through meiotic restitution or
      mitotic amphidiploidization. However, this technique has few applications to
      date, and it is un-known how N(2)O treatment restores fertility in sterile
      hybrids. To establish optimal N(2)O treatment conditions and determine its
      cytological mechanism of action, we treated various sized floral buds with N(2)O
      gas at different anther developmental stages from fertile and sterile hybrid
      lilies. N(2)O treatment using the optimal 1-4 mm floral buds induced mitotic
      polyploidization of male archesporial cells to produce 2n pollen in fertile
      hybrid lilies. In sterile hybrid lilies, N(2)O treatment doubled the chromosome
      number in male archesporial cells followed by homologous chromosome pairing and
      normal meiosis in pollen mother cells (PMC), resulting in restoration of pollen
      fertility. Backcrossing the resultant fertile pollen to Lilium * formolongi
      produced many triploid BC(1) plants. Thus N(2)O treatment at the archesporial
      cell proliferating stage effectively overcame pollen sterility in hybrid lilies,
      resulting in fertile, 2n pollen grains that could produce progeny. The procedure
      presented here will promote interspecific or interploidy hybridization of lilies.

PMID- 23136470
TI  - Fine mapping of stable QTLs related to eating quality in rice (Oryza sativa L.)
      by CSSLs harboring small target chromosomal segments.
AB  - Amylose content (AC) and viscosity profile are primary indices for evaluating
      eating and cooking qualities of rice grain. Using chromosome segment substitution
      lines (CSSLs), previous studies identified a QTL cluster of genes for rice eating
      and cooking quality in the interval R727-G1149 on chromosome 8. In this study we
      report two QTLs for viscosity parameters, respectively controlling setback
      viscosity (SBV) and consistency viscosity (CSV), located in the same interval
      using rapid viscosity analyzer (RVA) profile as an indicator of eating quality.
      Previously reported QTL for AC was dissected into two components with opposite
      genetic effects. Of four QTLs, qCSV-8 and qAC-8-2 had stable genetic effects
      across three and four environments, respectively. qSBV-8, qCSV-8 and qAC-8-1
      partly overlapped, but were separated from qAC-8-2. Based on data from an
      Affymetrix rice GeneChip, two genes related to starch biosynthesis at the qAC-8-2
      locus were chosen for further quantitative expression analysis. Both genes showed
      enhanced expression in sub-CSSLs carrying the target qAC-8-2 allele, but not in
      sub-CSSLs without the target qAC-8-2 allele, indicating their possible role in
      rice quality determination. Molecular markers closely linked to the two stable
      QTL provide the opportunity for marker-assisted selection (MAS) in breeding high
      quality rice.

PMID- 23136471
TI  - Applicability of Aegilops tauschii drought tolerance traits to breeding of
      hexaploid wheat.
AB  - Few genes are available to develop drought-tolerant bread wheat (Triticum
      aestivum L.) cultivars. One way to enhance bread wheat's genetic diversity would
      be to take advantage of the diversity of wild species by creating synthetic
      hexaploid wheat (SW) with the genomic constitution of bread wheat. In this study,
      we compared the expression of traits encoded at different ploidy levels and
      evaluated the applicability of Aegilops tauschii drought-related traits using 33
      Ae. tauschii accessions along with their corresponding SW lines under well
      watered and drought conditions. We found wide variation in Ae. tauschii, and even
      wider variation in the SW lines. Some SW lines were more drought-tolerant than
      the standard cultivar Cham 6. Aegilops tauschii from some regions gave better
      performing SW lines. The traits of Ae. tauschii were not significantly correlated
      with their corresponding SW lines, indicating that the traits expressed in wild
      diploid relatives of wheat may not predict the traits that will be expressed in
      SW lines derived from them. We suggest that, regardless of the adaptability and
      performance of the Ae. tauschii under drought, production of SW could probably
      result in genotypes with enhanced trait expression due to gene interactions, and
      that the traits of the synthetic should be evaluated in hexaploid level.

PMID- 23136472
TI  - Occurrence of metaxenia and false hybrids in Brassica juncea L. cv. Kikarashina *
      B. napus.
AB  - Imported genetically modified (GM) canola (Brassica napus) is approved by
      Japanese law. Some GM canola varieties have been found around importation sites,
      and there is public concern that these may have any harmful effects on related
      species such as reduction of wild relatives. Because B. juncea is distributed
      throughout Japan and is known to be high crossability with B. napus, it is
      assumed to be a recipient of B. napus. However, there are few reports for
      introgression of cross-combination in B. juncea * B. napus. To assess
      crossability, we artificially pollinated B. juncea with B. napus. After
      harvesting a large number of progeny seeds, we observed false hybrids and
      metaxenia of seed coats. Seed coat color was classified into four categories and
      false hybrids were confirmed by morphological characteristics and random
      amplified polymorphic DNA (RAPD) markers. Furthermore, the occurrence of false
      hybrids was affected by varietal differences in B. napus, whereas that of
      metaxenia was related to hybridity. Therefore, we suggest that metaxenia can be
      used as a marker for hybrid identification in B. juncea L. cv. Kikarashina * B.
      napus. Our results suggest that hybrid productivity in B. juncea * B. napus
      should not be evaluated by only seed productivity, crossability ought to be
      assessed the detection of true hybrids.

PMID- 23136473
TI  - Molecular and cytogenetic identification of new wheat-Dasypyrum breviaristatum
      additions conferring resistance to stem rust and powdery mildew.
AB  - Two cytologically stable wheat-Dasypyrum breviarisatatum addition lines, Y93-1-6
      6 and Y93-1-A6-4, were identified by integrated molecular and cytogenetic
      techniques. C-banding and genomic in situ hybridization (GISH) showed that Y93-1
      6-6 and Y93-1-A6-4 were different wheat-D. breviaristatum additions. A total of
      51 markers (primer/enzyme combinations), including 6 PCR-based Landmark Unique
      Gene (PLUG) markers and 45 Sequence-Tagged-Site (STS) markers, were selected from
      3,774 primer/enzyme combinations to further characterize these two additions.
      Marker haploytpes suggested that both D. breviaristatum chromosomes in Y93-1-6-6
      and Y93-1-A6-4 were rearranged. Stem rust resistance screening indicated that
      both additions were highly resistant to race RKQQC, whereas only Y93-1-6-6 was
      resistant to race TTKSK (Ug99). Powdery mildew resistance screening showed that
      only Y93-1-6-6 was resistant. Pedigree analysis suggested that the stem rust and
      powdery mildew resistance of Y93-1-6-6 was derived from D. breviaristatum,
      indicating that the D. breviaristatum chromosomes in Y93-1-6-6 possess a new
      powdery mildew resistance gene(s), and new stem rust resistance gene(s). These
      two additions could be used as stem rust or powdery mildew resistance sources in
      wheat breeding programs.

PMID- 23136474
TI  - Production and characterization of an alloplasmic and monosomic addition line of
      Brassica rapa carrying the cytoplasm and one chromosome of Moricandia arvensis.
AB  - Intergeneric hybridization was performed between Moricandia arvensis and four
      inbred lines of Brassica rapa following embryo rescue. Three F(1) hybrid plants
      were developed from three cross combinations of M. arvensis * B. rapa, and
      amphidiploids were synthesized by colchicine treatment. Six BC(1) plants were
      generated from a single cross combination of amphidipolid * B. rapa 'Ko1-303'
      through embryo rescue. One BC(2) and three BC(3) plants were obtained from
      successive backcrossing with B. rapa 'Ko1-303' employing embryo rescue.
      Alloplasmic and monosomic addition lines of B. rapa (Allo-MALs, 2n = 21) were
      obtained from backcrossed progeny of three BC(3) plants (2n = 21, 22 and 23)
      without embryo rescue. An alloplasmic line of B. rapa (2n = 20) degenerated
      before floliation on 1/2 MS medium due to severe chlorosis. Allo-MALs of B. rapa
      (2n = 21) showed stable male sterility without any abnormal traits in vegetative
      growth and female fertility. Molecular analyses revealed that the same chromosome
      and cytoplasm of M. arvensis had been added to each Allo-MAL of B. rapa. This
      Allo-MAL of B. rapa may be useful material for producing cytoplasmic male sterile
      lines of B. rapa.

PMID- 23136475
TI  - Genetic analysis of heterotic loci detected in a cross between indica and
      japonica rice (Oryza sativa L.).
AB  - The study on the genetic basis of heterosis has received significant attention in
      recent years. In this study, using a set of introgression lines (ILs) and
      corresponding testcross F(1) populations, we investigated heterotic loci (HL)
      associated with six yield-related traits in both Oryza sativa L. subsp. indica
      and japonica. A total of 41 HL were detected on the basis of mid-parent heterosis
      values with single-point analysis. The F(1) test-cross population showed
      superiority in most yield-related traits and was characterized by a high
      frequency of overdominant HL. Thirty-eight of the 41 HL were overdominant, and in
      the absence of epistasis, three HL were dominant, suggesting that heterotic
      effects at the single-locus level mainly appeared to be overdominant in rice.
      Twenty-four HL had a real positive effect, suggesting that they are viable
      candidates for the improvement of rice yield potential. Compared with the
      quantitative trait loci (QTLs) detected in the ILs, only six out of the 41
      (14.6%) HL were detected in QTL analysis under the same statistical threshold,
      indicating that heterosis and trait performance may be conditioned by different
      sets of loci.

PMID- 23136476
TI  - Effectiveness of combining resistance to Thielaviopsis basicola and Tomato
      spotted wilt virus in haploid tobacco genotypes.
AB  - Black root rot (BRR) caused by Thielaviopsis basicola as well as Tomato spotted
      wilt virus (TSWV) are the most serious problems in tobacco growing regions. We
      crossed the breeding line WGL 3 carrying BRR resistance derived from N.glauca
      with the line PW-834 the resistance of which to TSWV was transferred from
      cultivar Polalta. Anthers obtained from F(1) hybrid plants were cultured to
      induce haploids combining resistance to Th. basicola and TSWV. Flow cytometry
      analysis revealed 242 haploids and 2 spontaneous doubled haploids among
      regenerants. All haploids were cloned and then evaluated for BRR as well as TSWV
      resistance. The presence of pathogens was detected by microscopic evaluation of
      roots or using DAS-ELISA test. Microscopic assessment showed that, 132 haploids
      had no symptoms of Th. basicola which, together with the absence of symptoms in
      the F(1) hybrids, indicated a dominant monogenic mode of inheritance. At the same
      time only 30 haploids demonstrated resistance to TSWV. SCAR markers associated
      with TSWV resistance gene detection was applied. The results indicate that small
      proportion of TSWV-resistant haploids is probably due to the influence of
      deleterious genes flanking the resistance factor that reduced vitality of
      gametophytes. Altogether, 24 haploids showed multiple resistance to Th. basicola
      and TSWV.

PMID- 23136477
TI  - QTL analysis of photoperiod sensitivity in common buckwheat by using markers for
      expressed sequence tags and photoperiod-sensitivity candidate genes.
AB  - Photoperiod sensitivity is an important trait related to crop adaptation and
      ecological breeding in common buckwheat (Fagopyrum esculentum Moench). Although
      photoperiod sensitivity in this species is thought to be controlled by
      quantitative trait loci (QTLs), no genes or regions related to photoperiod
      sensitivity had been identified until now. Here, we identified QTLs controlling
      photoperiod sensitivity by QTL analysis in a segregating F(4) population (n =
      100) derived from a cross of two autogamous lines, 02AL113(Kyukei SC2)LH.self and
      C0408-0 RP. The F(4) progenies were genotyped with three markers for photoperiod
      sensitivity candidate genes, which were identified based on homology to
      photoperiod-sensitivity genes in Arabidopsis and 76 expressed sequence tag
      markers. Among the three photoperiod-sensitivity candidate genes (FeCCA1, FeELF3
      and FeCOL3) identified in common buckwheat, FeELF3 was associated with
      photoperiod sensitivity. Two EST regions, Fest_L0606_4 and Fest_L0337_6, were
      associated with photoperiod sensitivity and explained 20.0% and 14.2% of the
      phenotypic variation, respectively. For both EST regions, the allele from
      02AL113(Kyukei SC2)LH.self led to early flowering. An epistatic interaction was
      also confirmed between Fest_L0606_4 and Fest_L0337_6. These results demonstrate
      that photoperiod sensitivity in common buckwheat is controlled by a pathway
      consisting of photoperiod-sensitivity candidate genes as well as multiple gene
      action.

PMID- 23136478
TI  - Distribution of photoperiod-insensitive alleles Ppd-B1a and Ppd-D1a and their
      effect on heading time in Japanese wheat cultivars.
AB  - The genotypes of photoperiod response genes Ppd-B1 and Ppd-D1 in Japanese wheat
      cultivars were determined by a PCR-based method, and heading times were compared
      among genotypes. Most of the Japanese wheat cultivars, except those from the
      Hokkaido region, carried the photoperiod-insensitive allele Ppd-D1a, and heading
      was accelerated 10.3 days compared with the Ppd-D1b genotype. Early cultivars
      with Ppd-D1a may have been selected to avoid damage from preharvest rain. In the
      Hokkaido region, Ppd-D1a frequency was lower and heading date was late regardless
      of Ppd-D1 genotype, suggesting another genetic mechanism for late heading in
      Hokkaido cultivars. In this study, only 11 cultivars proved to carry Ppd-B1a, and
      all of them carried another photoperiod-insensitive allele, Ppd-D1a. The Ppd
      B1a/Ppd-D1a genotype headed 6.7 days earlier than the Ppd-B1b/Ppd-D1a genotype,
      indicating a significant effect of Ppd-B1a in the genetic background with Ppd
      D1a. Early-maturity breeding in Japan is believed to be accelerated by the
      introduction of the Ppd-B1a allele into medium-heading cultivars carrying Ppd
      D1a. Pedigree analysis showed that Ppd-B1a in three extra-early commercial
      cultivars was inherited from 'Shiroboro 21' by early-heading Chugoku lines bred
      at the Chugoku Agriculture Experimental Station.

PMID- 23136479
TI  - Development of genomic and EST-SSR markers in radish (Raphanus sativus L.).
AB  - Radish (Raphanus sativus L.) belongs to Brassicaceae family and is a close
      relative of Brassica. This species shows a wide morphological diversity, and is
      an important vegetable especially in Asia. However, molecular research of radish
      is behind compared to that of Brassica. For example, reports on SSR (simple
      sequence repeat) markers are limited. Here, we designed 417 radish SSR markers
      from SSR-enriched genomic libraries and the cDNA data. Of the 256 SSR markers
      succeeded in PCR, 130 showed clear polymorphisms between two radish lines; a rat
      tail radish and a Japanese cultivar, 'Harufuku'. As a test case for evaluation of
      the present SSRs, we conducted two studies. First, we selected 16 SSRs to
      calculate polymorphism information contents (PICs) using 16 radish cultivars and
      four other Brassicaceae species. These markers detected 3-15 alleles (average =
      9.6). PIC values ranged from 0.54 to 0.92 (average = 0.78). Second, part of the
      present SSRs were tested for mapping using our previously-examined mapping
      population. The map spanned 672.7 cM with nine linkage groups (LGs). The 21
      radish SSR markers were distributed throughout the LGs. The SSR markers developed
      here would be informative and useful for genetic analysis in radish and its
      related species.

PMID- 23136480
TI  - Strawberry cultivar identification based on hypervariable SSR markers.
AB  - We genotyped strawberry cultivars by two newly selected and two previously
      reported SSR markers. All four markers produced interpretable electropherograms
      from 75 accessions consisting of 72 Fragaria * ananassa cultivars or lines and
      three octoploid Fragaria species accessions. These SSR markers were highly
      polymorphic; in particular, one of the newly developed markers, FxaHGA02P13, was
      capable of distinguishing all of the accessions except for a mutant strain that
      was derived from another accession in the set. When two markers were combined,
      all 48 full-sib individuals could be distinguished. Fingerprinting patterns were
      reproducible between multiple samples, including the leaves, sepals, and fruit
      flesh of the same accession. Principal-coordinate analysis of the 75 accessions
      detected several groups, which reflect taxon and breeding site. Together with
      other available markers, these SSR markers will contribute to the management of
      strawberry genetic resources and the protection of breeders' rights.

PMID- 23136481
TI  - A maternally inherited DNA marker, descended from Solanum demissum (2n = 6x = 72)
      to S. tuberosum (2n = 4x = 48).
AB  - A Mexican hexaploid wild potato species, Solanum demissum (dms), was only used as
      a female in previous breeding programs. The resulting clones with dms cytoplasm
      produced abundant, but non-functional pollen. A 170 bp DNA fragment, named Band
      1, was originally detected in the F(1) hybrid between dms and S. tuberosum. In
      this study, the sequenced region was extended to 1,032 bp; nevertheless, it did
      not show any homology to known sequences. This extended region harboring Band 1
      was, without introns, all transcribed to mRNA and was maternally inherited from
      dms to S. tuberosum through backcrosses. Three dms accessions, 168 accessions of
      38 cultivated and closely related wild species, and 158 varieties and breeding
      lines were surveyed, which demonstrated that Band 1 was specific to dms and
      varieties and breeding lines with dms cytoplasm. Thus, Band 1 is a useful marker
      to distinguish dms cytoplasm, which enables us to design efficient mating
      combinations in breeding programs.

PMID- 23136482
TI  - Breeding Science Special Issue: Soybean breeding in genomic era.

PMID- 23136483
TI  - Evolutionary and comparative analyses of the soybean genome.
AB  - The soybean genome assembly has been available since the end of 2008. Significant
      features of the genome include large, gene-poor, repeat-dense pericentromeric
      regions, spanning roughly 57% of the genome sequence; a relatively large genome
      size of ~1.15 billion bases; remnants of a genome duplication that occurred ~13
      million years ago (Mya); and fainter remnants of older polyploidies that occurred
      ~58 Mya and >130 Mya. The genome sequence has been used to identify the genetic
      basis for numerous traits, including disease resistance, nutritional
      characteristics, and developmental features. The genome sequence has provided a
      scaffold for placement of many genomic feature elements, both from within soybean
      and from related species. These may be accessed at several websites, including
      http://www.phytozome.net, http://soybase.org, http://comparative-legumes.org, and
      http://www.legumebase.brc.miyazaki-u.ac.jp. The taxonomic position of soybean in
      the Phaseoleae tribe of the legumes means that there are approximately two dozen
      other beans and relatives that have undergone independent domestication, and
      which may have traits that will be useful for transfer to soybean. Methods of
      translating information between species in the Phaseoleae range from design of
      markers for marker assisted selection, to transformation with Agrobacterium or
      with other experimental transformation methods.

PMID- 23136484
TI  - Tracing soybean domestication history: From nucleotide to genome.
AB  - Since the genome sequences of wild species may provide key information about the
      genetic elements involved in speciation and domestication, the undomesticated
      soybean (Glycine soja Sieb. and Zucc.), a wild relative of the current cultivated
      soybean (G. max), was sequenced. In contrast to the current hypothesis of soybean
      domestication, which holds that the current cultivated soybean was domesticated
      from G. soja, our previous work has suggested that soybean was domesticated from
      the G. soja/G. max complex that diverged from a common ancestor of these two
      species of Glycine. In this review, many structural genomic differences between
      the two genomes are described and a total of 705 genes are identified as
      structural variations (SVs) between G. max and G. soja. After protein families
      database of alignments and hidden Markov models IDs and gene ontology terms were
      assigned, many interesting genes are discussed in detail using four domestication
      related traits, such as flowering time, transcriptional factors, carbon
      metabolism and disease resistance. Soybean domestication history is explored by
      studying these SVs in genes. Analysis of SVs in genes at the population-level may
      clarify the domestication history of soybean.

PMID- 23136485
TI  - The National BioResource Project (NBRP) Lotus and Glycine in Japan.
AB  - The objective of the National BioResource Project (NBRP) in Japan is to collect,
      conserve and distribute biological materials for life sciences research. The
      project consists of twenty-eight bioresources, including animal, plant,
      microorganism and DNA resources. NBRP Lotus and Glycine aims to support the
      development of legume research through the collection, conservation, and
      distribution of these bioresources. Lotus japonicus is a perennial legume that
      grows naturally throughout Japan and is widely used as a model plant for legumes
      because of such advantages as its small genome size and short life cycle. Soybean
      (Glycine max) has been cultivated as an important crop since ancient times, and
      numerous research programs have generated a large amount of basic research
      information and valuable bioresources for this crop. We have also developed a
      "LegumeBase" a specialized database for the genera Lotus and Glycine, and are
      maintaining this database as a part of the NBRP. In this paper we will provide an
      overview of the resources available from the NBRP Lotus and Glycine database
      site, called "LegumeBase".

PMID- 23136486
TI  - Potential of a mutant-based reverse genetic approach for functional genomics and
      molecular breeding in soybean.
AB  - Mutant-based reverse genetics offers a powerful way to create novel mutant
      alleles at a selected locus. This approach makes it possible to directly identify
      plants that carry a specific modified gene from the nucleotide sequence data.
      Soybean [Glycine max (L.) Merr.] has a highly redundant paleopolyploid genome
      (approx. 1.1 Gb), which was completely sequenced in 2010. Using reverse genetics
      to support functional genomics studies designed to predict gene function would
      accelerate post-genomics research in soybean. Furthermore, the novel mutant
      alleles created by this approach would be useful genetic resources for improving
      various traits in soybean. A reverse genetic screening platform in soybean has
      been developed that combines more than 40,000 mutant lines with a high-throughput
      method, Targeting Local Lesions IN Genome (TILLING). In this review, the mutant
      based reverse genetic approach based on this platform is described, and the
      likely evolution of this approach in the near future.

PMID- 23136487
TI  - RNA silencing as a tool to uncover gene function and engineer novel traits in
      soybean.
AB  - RNA silencing refers collectively to diverse RNA-mediated pathways of nucleotide
      sequence-specific inhibition of gene expression. It has been used to analyze gene
      function and engineer novel traits in various organisms. Here, we review the
      application of RNA silencing in soybean. To produce soybean lines, in which a
      particular gene is stably silenced, researchers have frequently used a transgene
      that transcribes inverted repeats of a target gene segment. Suppression of gene
      expression in developing soybean embryos has been one of the main focuses of
      metabolic engineering using transgene-induced silencing. Plants that have
      enhanced resistance against diseases caused by viruses or cyst nematode have also
      been produced. Meanwhile, Agrobacterium rhizogenes-mediated transformation has
      been used to induce RNA silencing in roots, which enabled analysis of the roles
      of gene products in nodulation or disease resistance. RNA silencing has also been
      induced using viral vectors, which is particularly useful for gene function
      analysis. So far, three viral vectors for virus-induced gene silencing have been
      developed for soybean. One of the features of the soybean genome is the presence
      of a large number of duplicated genes. Potential use of RNA silencing technology
      in combination with forward genetic approaches for analyzing duplicated genes is
      discussed.

PMID- 23136488
TI  - Recent advances in soybean transformation and their application to molecular
      breeding and genomic analysis.
AB  - Herbicide-resistant transgenic soybean plants hold a leading market share in the
      USA and other countries, but soybean has been regarded as recalcitrant to
      transformation for many years. The cumulative and, at times, exponential advances
      in genetic manipulation have made possible further choices for soybean
      transformation. The most widely and routinely used transformation systems are
      cotyledonary node-Agrobacterium-mediated transformation and somatic embryo
      particle-bombardment-mediated transformation. These ready systems enable us to
      improve seed qualities and agronomic characteristics by transgenic approaches. In
      addition, with the accumulation of soybean genomic resources, convenient or
      promising approaches will be requisite for the determination and use of gene
      function in soybean. In this article, we describe recent advances in and problems
      of soybean transformation, and survey the current transgenic approaches for
      applied and basic research in Japan.

PMID- 23136489
TI  - Genome-wide genetic dissection of germplasm resources and implications for
      breeding by design in soybean.
AB  - "Breeding by Design" as a concept described by Peleman and van der Voort aims to
      bring together superior alleles for all genes of agronomic importance from
      potential genetic resources. This might be achievable through high-resolution
      allele detection based on precise QTL (quantitative trait locus/loci) mapping of
      potential parental resources. The present paper reviews the works at the Chinese
      National Center for Soybean Improvement (NCSI) on exploration of QTL and their
      superior alleles of agronomic traits for genetic dissection of germplasm
      resources in soybeans towards practicing "Breeding by Design". Among the major
      germplasm resources, i.e. released commercial cultivar (RC), farmers' landrace
      (LR) and annual wild soybean accession (WS), the RC was recognized as the primary
      potential adapted parental sources, with a great number of new alleles (45.9%)
      having emerged and accumulated during the 90 years' scientific breeding
      processes. A mapping strategy, i.e. a full model procedure (including additive
      (A), epistasis (AA), A * environment (E) and AA * E effects), scanning with
      QTLNetwork2.0 and followed by verification with other procedures, was suggested
      and used for the experimental data when the underlying genetic model was usually
      unknown. In total, 110 data sets of 81 agronomically important traits were
      analyzed for their QTL, with 14.5% of the data sets showing major QTL
      (contribution rate more than 10.0% for each QTL), 55.5% showing a few major QTL
      but more small QTL, and 30.0% having only small QTL. In addition to the detected
      QTL, the collective unmapped minor QTL sometimes accounted for more than 50% of
      the genetic variation in a number of traits. Integrated with linkage mapping,
      association mappings were conducted on germplasm populations and validated to be
      able to provide complete information on multiple QTL and their multiple alleles.
      Accordingly, the QTL and their alleles of agronomic traits for large samples of
      RC, LR and WS were identified and then the QTL-allele matrices were established.
      Based on which the parental materials can be chosen for complementary
      recombination among loci and alleles to make the crossing plans genetically
      optimized. This approach has provided a way towards breeding by design, but the
      accuracy will depend on the precision of the loci and allele matrices.

PMID- 23136490
TI  - Pathogenic diversity of Phytophthora sojae and breeding strategies to develop
      Phytophthora-resistant soybeans.
AB  - Phytophthora stem and root rot, caused by Phytophthora sojae, is one of the most
      destructive diseases of soybean [Glycine max (L.) Merr.], and the incidence of
      this disease has been increasing in several soybean-producing areas around the
      world. This presents serious limitations for soybean production, with yield
      losses from 4 to 100%. The most effective method to reduce damage would be to
      grow Phytophthora-resistant soybean cultivars, and two types of host resistance
      have been described. Race-specific resistance conditioned by single dominant Rps
      ("resistance to Phytophthora sojae") genes and quantitatively inherited partial
      resistance conferred by multiple genes could both provide protection from the
      pathogen. Molecular markers linked to Rps genes or quantitative trait loci (QTLs)
      underlying partial resistance have been identified on several molecular linkage
      groups corresponding to chromosomes. These markers can be used to screen for
      Phytophthora-resistant plants rapidly and efficiently, and to combine multiple
      resistance genes in the same background. This paper reviews what is currently
      known about pathogenic races of P. sojae in the USA and Japan, selection of
      sources of Rps genes or minor genes providing partial resistance, and the current
      state and future scope of breeding Phytophthora-resistant soybean cultivars.

PMID- 23136491
TI  - Suppressive mechanism of seed coat pigmentation in yellow soybean.
AB  - In soybean seeds, numerous variations in colors and pigmentation patterns exist,
      most of which are observed in the seed coat. Patterns of seed coat pigmentation
      are determined by four alleles (I, i(i), i(k) and i) of the classically defined I
      locus, which controls the spatial distribution of anthocyanins and
      proanthocyanidins in the seed coat. Most commercial soybean cultivars produce
      yellow seeds with yellow cotyledons and nonpigmented seed coats, which are
      important traits of high-quality seeds. Plants carrying the I or i(i) allele show
      complete inhibition of pigmentation in the seed coat or pigmentation only in the
      hilum, respectively, resulting in a yellow seed phenotype. Classical genetic
      analyses of the I locus were performed in the 1920s and 1930s but, until
      recently, the molecular mechanism by which the I locus regulated seed coat
      pigmentation remained unclear. In this review, we provide an overview of the
      molecular suppressive mechanism of seed coat pigmentation in yellow soybean, with
      the main focus on the effect of the I allele. In addition, we discuss seed coat
      pigmentation phenomena in yellow soybean and their relationship to inhibition of
      I allele action.

PMID- 23136492
TI  - Genetic and molecular bases of photoperiod responses of flowering in soybean.
AB  - Flowering is one of the most important processes involved in crop adaptation and
      productivity. A number of major genes and quantitative trait loci (QTLs) for
      flowering have been reported in soybean (Glycine max). These genes and QTLs
      interact with one another and with the environment to greatly influence not only
      flowering and maturity but also plant morphology, final yield, and stress
      tolerance. The information available on the soybean genome sequence and on the
      molecular bases of flowering in Arabidopsis will undoubtedly facilitate the
      molecular dissection of flowering in soybean. Here, we review the present status
      of our understanding of the genetic and molecular mechanisms of flowering in
      soybean. We also discuss our identification of orthologs of Arabidopsis flowering
      genes from among the 46,367 genes annotated in the publicly available soybean
      genome database Phytozome Glyma 1.0. We emphasize the usefulness of a combined
      approach including QTL analysis, fine mapping, and use of candidate gene
      information from model plant species in genetic and molecular studies of soybean
      flowering.

PMID- 23136493
TI  - Rj (rj) genes involved in nitrogen-fixing root nodule formation in soybean.
AB  - It has long been known that formation of symbiotic root nodules in soybean
      (Glycine max (L.) Merr.) is controlled by several host genes referred to as Rj
      (rj) genes, but molecular cloning of these genes has been hampered by soybean's
      complicated genome structure and large genome size. Progress in molecular
      identification of legume genes involved in root nodule symbiosis have been mostly
      achieved by using two model legumes, Lotus japonicus and Medicago truncatula,
      that have relatively simple and small genomes and are capable of molecular
      transfection. However, recent development of resources for soybean molecular
      genetic research, such as genome sequencing, large EST databases, and high
      density linkage maps, have enabled us to isolate several Rj genes. This progress
      has been achieved in connection with systematic utilization of the information
      obtained from molecular genetics of the model legumes. In this review, we
      summarize the current status of knowledge of host-controlled nodulation in
      soybean based on information from recent studies on Rj genes, and discuss the
      future research prospects.

PMID- 23136494
TI  - Mapping and use of QTLs controlling pod dehiscence in soybean.
AB  - While the cultivated soybean, Glycine max (L.) Merr., is more recalcitrant to pod
      dehiscence (shattering-resistant) than wild soybean, Glycine soja Sieb. & Zucc.,
      there is also significant genetic variation in shattering resistance among
      cultivated soybean cultivars. To reveal the genetic basis and develop DNA markers
      for pod dehiscence, several research groups have conducted quantitative trait
      locus (QTL) analysis using segregated populations derived from crosses between G.
      max accessions or between a G. max and G. soja accession. In the populations of
      G. max, a major QTL was repeatedly identified near SSR marker Sat_366 on linkage
      group J (chromosome 16). Minor QTLs were also detected in several studies,
      although less commonality was found for the magnitudes of effect and location. In
      G. max * G. soja populations, only QTLs with a relatively small effect were
      detected. The major QTL found in G. max was further fine-mapped, leading to the
      development of specific markers for the shattering resistance allele at this
      locus. The markers were used in a breeding program, resulting in the production
      of near-isogenic lines with shattering resistance and genetic backgrounds of
      Japanese elite cultivars. The markers and lines developed will hopefully
      contribute to the rapid production of a variety of shattering-resistant soybean
      cultivars.

PMID- 23136495
TI  - Genetic studies on saline and sodic tolerances in soybean.
AB  - Salt-affected soils are generally classified into two main categories: saline and
      sodic (alkaline). Developing and using soybean (Glycine max (L.) Merr) cultivars
      with high salt tolerance is an effective way of maintaining sustainable
      production in areas where soybean growth is threatened by salt stress. Early
      classical genetics studies revealed that saline tolerance was conditioned by a
      single dominant gene. Recently, a series of studies consistently revealed a major
      quantitative trait locus (QTL) for saline tolerance located on linkage group N
      (chromosome 3) around the SSR markers Satt255 and Sat_091; other minor QTLs were
      also reported. In the case of sodic tolerance, most studies focused on iron
      deficiency caused by a high soil pH, and several QTLs associated with iron
      deficiency were identified. A wild soybean (Glycine soja Sieb. & Zucc.) accession
      with high sodic tolerance was recently identified, and a significant QTL for
      sodic tolerance was detected on linkage group D2 (chromosome 17). These studies
      demonstrated that saline and sodic tolerances were controlled by different genes
      in soybean. DNA markers closely associated with these QTLs can be used for marker
      assisted selection to pyramid tolerance genes in soybean for both saline and
      sodic stresses.

PMID- 23136496
TI  - Evaluation of soybean germplasm conserved in NIAS genebank and development of
      mini core collections.
AB  - Genetic variation and population structure among 1603 soybean accessions,
      consisted of 832 Japanese landraces, 109 old and 57 recent Japanese varieties,
      341 landrace from 16 Asian countries and 264 wild soybean accessions, were
      characterized using 191 SNP markers. Although gene diversity of Japanese soybean
      germplasm was slight lower than that of exotic soybean germplasm, population
      differentiation and clustering analyses indicated clear genetic differentiation
      among Japanese cultivated soybeans, exotic cultivated soybeans and wild soybeans.
      Nine hundred ninety eight Japanese accessions were separated to a certain extent
      into groups corresponding to their agro-morphologic characteristics such as
      photosensitivity and seed characteristics rather than their geographical origin.
      Based on the assessment of the SNP markers and several agro-morphologic traits,
      accessions that retain gene diversity of the whole collection were selected to
      develop several soybean sets of different sizes using an heuristic approach; a
      minimum of 12 accessions can represent the observed gene diversity; a mini-core
      collection of 96 accession can represent a major proportion of both geographic
      origin and agro-morphologic trait variation. These selected sets of germplasm
      will provide an effective platform for enhancing soybean diversity studies and
      assist in finding novel traits for crop improvement.

PMID- 23136497
TI  - Diversity and population structure of black soybean landraces originating from
      Tanba and neighboring regions.
AB  - Black soybean landraces that had been cultivated in Tanba region and the
      neighboring regions and conserved black soybean landraces, including those from
      other regions in Japan, were used in this study. The polymorphisms of 78 SSR
      markers in nuclear DNA and 6 SSRs in chloroplast DNA were analyzed in the black
      soybean landrace populations. The result of phylogenic analysis revealed that the
      black soybeans can be classified into six clades. The landraces originating from
      Tanba region were classed into first and second clades, and two chloroplast
      genotypes were found in the population of black soybeans from the Tanba region.
      Genotype A chloroplast was predominantly identified in major populations of the
      Tanba, while genotype B was widely distributed in the black soybean population.
      Population structure analysis in the Japanese black soybean accessions inferred
      there are six groups. The black soybean landrace from the Tanba region was
      classified into three groups, mainly corresponding to the distance-based
      phylogenic results. The two groups were probably derived from different ancestors
      with Type A and B chloroplast genomes, respectively, whereas the other group
      showed both types of chloroplast genome. The admixture situations suggested that
      the landraces in the main group have been widely cultivated in Tanba region,
      while the landraces that belong to other groups were cultivated in localized
      area. Several phenotypes were compared among genotype groups, dividing into two
      sub-groups: founder sub-group and admixed sub-group. Phenotypic differences were
      observed between founder landraces in group 1 and group 3. On the other hand,
      landraces in admixture landraces in group 1 and group 2 segregated for several
      traits, while founder landraces in group 1 were stabled for each trait. These
      observations suggest that gene flow events have occurred between different
      founder landraces.

PMID- 23136498
TI  - Genetic relationships of soybean cyst nematode resistance originated in
      Gedenshirazu and PI84751 on Rhg1 and Rhg4 loci.
AB  - Soybean cyst nematode (SCN) (Heterodera glycines Ichinohe) is one of the most
      damaging pests of soybean (Glycine max (L.) Merr.). Host plant resistance has
      been the most effective control method. Because of the spread of multiple SCN
      races in Hokkaido, the Tokachi Agricultural Experiment Station has bred soybeans
      for SCN resistance since 1953 by using 2 main resistance resources PI84751
      (resistant to races 1 and 3) and Gedenshirazu (resistant to race 3). In this
      study, we investigated the genetic relationships of SCN resistance originating
      from major SCN resistance genes in Gedenshirazu and PI84751 by using SSR markers.
      We confirmed that race 1 resistance in PI84751 was independently controlled by 4
      genes, 2 of which were rhg1 and Rhg4. We classified the PI84751- type allele of
      Rhg1 as rhg1-s and the Gedenshirazu-type allele of Rhg1 as rhg1-g. In the cross
      of the Gedenshirazu-derived race 3-resistant lines and the PI84751-derived races
      1- and 3-resistant lines, the presence of rhg1-s and Rhg4 was responsible for
      race 1-resistance. These results indicated that it was possible to select race 1
      resistant plants by using marker-assisted selection for the rhg1-s and Rhg4
      alleles through a PI84751 origin * Gedenshirazu origin cross.

PMID- 23136499
TI  - Genetic analysis of antixenosis resistance to the common cutworm (Spodoptera
      litura Fabricius) and its relationship with pubescence characteristics in soybean
      (Glycine max (L.) Merr.).
AB  - The common cutworm (CCW, Spodoptera litura Fabricius) is one of the most serious
      pests of soybean (Glycine max (L.) Merr.). Previously, two quantitative trait
      loci (QTLs) for antibiosis resistance to CCW, CCW-1 and CCW-2, were detected in
      the resistant cultivar Himeshirazu. In this study, we conducted an anti-xenosis
      bioassay using a recombinant inbred population derived from a cross between a
      susceptible cultivar Fukuyutaka and Himeshirazu to perform QTL analysis. Two QTLs
      for antixenosis resistance, qRslx1 and qRslx2, were identified on Chrs 7 and 12,
      and the resistant alleles of qRslx1 and qRslx2 were derived from Himeshirazu and
      Fukuyutaka, respectively. The position of qRslx1 is similar to that of CCW-1. We
      also analyzed pubescence characteristics because they have been reported to be
      associated with soybean insect resistance. Two QTLs for pubescence length (on
      Chrs 7 and 12) and two QTLs for pubescence density (on Chrs 1 and 12) were
      identified. The pubescence QTLs on Chrs 7 and 12 were located near qRslx1 and
      qRslx2, respectively. These results suggest that the antixenosis resistance could
      be controlled genetically by the identified QTLs and that the pubescence
      characteristics might contribute to the soybean antixenosis resistance to CCW.

PMID- 23136500
TI  - Fine mapping of foxglove aphid (Aulacorthum solani) resistance gene Raso1 in
      soybean and its effect on tolerance to Soybean dwarf virus transmitted by
      foxglove aphid.
AB  - Soybean dwarf virus (SbDV) causes serious dwarfing, yellowing and sterility in
      soybean (Glycine max). The soybean cv. Adams is tolerant to SbDV infection in the
      field and exhibits antibiosis to foxglove aphid (Aulacorthum solani), which
      transmits SbDV. This antibiosis (termed "aphid resistance") is required for
      tolerance to SbDV in the field in segregated progenies of Adams. A major
      quantitative trait locus, Raso1, is reported for foxglove aphid resistance. Our
      objectives were to fine map Raso1 and to reveal whether Raso1 alone is sufficient
      to confer both aphid resistance and SbDV tolerance. We introduced Raso1 into cv.
      Toyomusume by backcrossing and investigated the degree of aphid antibiosis to
      foxglove aphid and the degree of tolerance to SbDV in the field. All Raso1
      introduced backcross lines showed aphid resistance. Interestingly, only one Raso1
      introduced backcross line (TM-1386) showed tolerance to SbDV in the field. The
      results demonstrated Raso1 alone is sufficient to confer aphid resistance but
      insufficient for SbDV tolerance. Tolerance to SbDV was indicated to require
      additional gene(s) to Raso1. Additionally, Raso1 was mapped to a 63-kb interval
      on chromosome 3 of the Williams 82 sequence assembly (Glyma1). This interval
      includes a nucleotide-binding site-leucine-rich repeat encoding gene and two
      other genes in the Williams 82 soybean genome sequence.

PMID- 23136501
TI  - Screening and genetic analysis of resistance to peanut stunt virus in soybean:
      identification of the putative Rpsv1 resistance gene.
AB  - The peanut stunt virus (PSV) causes yield losses in soybean and reduced seed
      quality due to seed mottling. The objectives of this study were to determine the
      phenotypic reactions of soybean germplasms to inoculation with two PSV isolates
      (PSV-K, PSV-T), the inheritance of PSV resistance in soybean cultivars, and the
      locus of the PSV resistance gene. We investigated the PSV resistance of 132
      soybean cultivars to both PSV isolates; of these, 73 cultivars exhibited
      resistance to both PSV isolates. Three resistant cultivars (Harosoy,
      Tsurunotamago 1 and Hyuga) were crossed with the susceptible cultivar Enrei. The
      crosses were evaluated in the F(1), F(2) and F(2:3) generations for their
      reactions to inoculation with the two PSV isolates. In an allelism test, we
      crossed Harosoy and Tsurunotamago 1 with the resistant cultivar Hyuga. The
      results revealed that PSV resistance in these cultivars is controlled by a single
      dominant gene at the same locus. We have proposed Rpsv1, as the name of the
      resistance gene in Hyuga. We also constructed a linkage map using recombinant
      inbred lines between Hyuga * Enrei using 176 SSR markers. We mapped Rpsv1 near
      the Satt435 locus on soybean chromosome 7.

PMID- 23136502
TI  - Molecular characterization of two high-palmitic-acid mutant loci induced by X-ray
      irradiation in soybean.
AB  - Palmitic acid is the most abundant (approx. 11% of total fatty acids) saturated
      fatty acid in conventional soybean seed oil. Increasing the saturated acid
      content of soybean oil improves its oxidative stability and plasticity. We have
      developed three soybean mutants with high palmitic acid content by X-ray
      irradiation. In this study, we successfully identified the mutated sites of two
      of these high-palmitic-acid mutants, J10 and M22. PCR-based mutant analysis
      revealed that J10 has a 206,203-bp-long deletion that includes the GmKASIIA gene
      and 16 other predicted genes, and M22 has a 26-bp-long deletion in the sixth
      intron of GmKASIIB. The small deletion in M22 causes mis-splicing of GmKASIIB
      transcripts, which should result in nonfunctional products. In addition, we
      designed co-dominant marker sets for these mutant alleles and confirmed the
      association of genotypes and palmitic acid contents in F(2) seeds of J10 X M22.
      This information will be useful in breeding programs to develop novel soybean
      cultivars with improved palmitic acid content. However, in the third mutant, KK7,
      we found no polymorphism in either GmKASIIA or GmKASIIB, which suggests that
      several unknown genes in addition to GmKASIIA and GmKASIIB may be involved in
      elevating the palmitic acid content of soybean seed oil.

PMID- 23136503
TI  - Genetic analysis of variations in the sugar chain composition at the C-3 position
      of soybean seed saponins.
AB  - Saponins are sterols or triterpene glycosides that are widely distributed in
      plants. The biosynthesis of soybean saponins is thought to involve many kinds of
      glycosyltransferases, which is reflected in their structural diversity. Here, we
      performed linkage analyses of the Sg-3 and Sg-4 loci, which may control the sugar
      chain composition at the C-3 sugar moieties of the soybean saponin aglycones
      soyasapogenols A and B. The Sg-3 locus, which controls the production of group A
      saponin Af, was mapped to chromosome (Chr-) 10. The Sg-4 locus, which controls
      the production of DDMP saponin betaa, was mapped to Chr-1. To elucidate the
      preference of sugar chain formation at the C-3 and C-22 positions, we analyzed
      the F(2) population derived from a cross between a mutant variety, Kinusayaka (sg
      1(0)), for the sugar chain structure at C-22 position, and Mikuriya-ao (sg-3),
      with respect to the segregation of the composition of the group A saponins, and
      found that the formation of these sugar chains was independently regulated.
      Furthermore, a novel saponin, predicted to be A0-gammag, 3-O-[beta-d
      galactopyranosyl (1->2)-beta-d-glucuronopyranosyl]-22-O-alpha-l-arabinopyranosyl
      soyasapogenol A, appeared in the hypocotyl of F(2) individuals with genotype sg
      1(0)/sg-1(0)sg-3/sg-3.

PMID- 23136504
TI  - Identification of QTL controlling post-flowering period in soybean.
AB  - The length of the reproductive period affects the grain yield of soybean (Glycine
      max [L.] Merr), and genetic control of the period might contribute to yield
      improvement. To detect genetic factor(s) controlling the reproductive period, a
      population of recombinant inbred lines (RILs) was developed from a cross between
      Japanese landrace 'Ippon-Sangoh' and, Japanese cultivar 'Fukuyutaka' which differ
      in their duration from flowering to maturation (DFM) relative to the difference
      in the duration from sowing to flowering (DSF). In the RIL population, the DFM
      correlated poorly (r = -0.16 to 0.34) with the DSF in all field trials over 3
      years. Two stable QTLs for the DFM on chromosomes (Chr-) 10 and 11 as well as two
      stable QTLs for the DSF on Chr-10 and -16 were identified. The QTL on Chr-11 for
      the reproductive period (designated as qDfm1; quantitative trait locus for
      duration from flowering to maturation 1) affected all three trials, and the
      difference in the DFM between the Fukuyutaka and Ippon-Sangoh was mainly
      accounted for qDfm1, in which the Fukuyutaka allele promoted a longer period.
      qDfm1 affected predominantly the reproductive period, and thus it might be
      possible to alter the period with little influence on the vegetative period.

PMID- 23136505
TI  - Effects on flowering and seed yield of dominant alleles at maturity loci E2 and
      E3 in a Japanese cultivar, Enrei.
AB  - 'Enrei' is the second leading variety of soybean (Glycine max (L.) Merr.) in
      Japan. Its cultivation area is mainly restricted to the Hokuriku region. In order
      to expand the adaptability of 'Enrei', we developed two near-isogenic lines
      (NILs) of 'Enrei' for the dominant alleles controlling late flowering at the
      maturity loci, E2 and E3, by backcrossing with marker-assisted selection. The
      resultant NILs and the original variety were evaluated for flowering, maturity,
      seed productivity and other agronomic traits in five different locations.
      Expectedly, NILs with E2 or E3 alleles flowered later than the original variety
      in most locations. These NILs produced comparatively larger plants in all
      locations. Seed yields were improved by E2 and E3 in the southern location or in
      late-sowing conditions, whereas the NIL for E2 exhibited almost the same or lower
      productivity in the northern locations due to higher degrees of lodging. Seed
      quality-related traits, such as 100-seed weight and protein content, were not
      significantly different between the original variety and its NILs. These results
      suggest that the modification of genotypes at maturity loci provides new
      varieties that are adaptive to environments of different latitudes while
      retaining almost the same seed quality as that of the original.

PMID- 23136506
TI  - DaizuBase, an integrated soybean genome database including BAC-based physical
      maps.
AB  - Soybean [Glycine max (L) Merrill] is one of the most important leguminous crops
      and ranks fourth after to rice, wheat and maize in terms of world crop
      production. Soybean contains abundant protein and oil, which makes it a major
      source of nutritious food, livestock feed and industrial products. In Japan,
      soybean is also an important source of traditional staples such as tofu, natto,
      miso and soy sauce. The soybean genome was determined in 2010. With its enormous
      size, physical mapping and genome sequencing are the most effective approaches
      towards understanding the structure and function of the soybean genome. We
      constructed bacterial artificial chromosome (BAC) libraries from the Japanese
      soybean cultivar, Enrei. The end-sequences of approximately 100,000 BAC clones
      were analyzed and used for construction of a BAC-based physical map of the
      genome. BLAST analysis between Enrei BAC-end sequences and the Williams82 genome
      was carried out to increase the saturation of the map. This physical map will be
      used to characterize the genome structure of Japanese soybean cultivars, to
      develop methods for the isolation of agronomically important genes and to
      facilitate comparative soybean genome research. The current status of physical
      mapping of the soybean genome and construction of database are presented.

PMID- 23136507
TI  - PAG and the latest trends in breeding research.

PMID- 23136508
TI  - Accurate evaluation and verification of varietal ranking for flooding tolerance
      at the seedling stage in barley (Hordeum vulgare L.).
AB  - Soil flooding or waterlogging is a major abiotic stress in upland crops. In
      barley, there have been several reported studies of selection for flooding
      tolerant genotypes, but it is difficult to obtain varietal rankings that are
      consistent among researchers. Our objectives were to establish experimental
      conditions that could be applied by other research groups and to verify the
      varietal ranking conducted in an earlier study. We conducted greenhouse
      experiments on 14 barley varieties. At the 2.5-leaf stage, they were flooded with
      0% or 0.1% soluble starch solution (mimicking reducing conditions). At 13 to 15
      days after the start of treatment, the degree of leaf injury and the shoot dry
      weight ratio (treatment:control) were recorded. Reliable and highly repeatable
      results were obtained for the criterion of leaf injury under reducing conditions,
      whereas shoot dry weight ratio was unstable. The varieties OUJ820 and OUA301 were
      highly tolerant, whereas OUA002 and OUJ247 were sensitive; these results matched
      those of the earlier study. The experimental conditions that we developed here
      may be useful for selection testing and genetic analysis of flooding tolerance in
      other laboratories.

PMID- 23136509
TI  - Evaluation of the effects of five QTL regions on Fusarium head blight resistance
      and agronomic traits in spring wheat (Triticum aestivum L.).
AB  - Fusarium head blight (FHB) is an important disease of wheat (Triticum aestivum
      L.). The aim of this study was to determine the effects of quantitative trait
      locus (QTL) regions for resistance to FHB and estimate their effects on reducing
      FHB damage to wheat in Hokkaido, northern Japan. We examined 233 F(1)-derived
      doubled-haploid (DH) lines from a cross between 'Kukeiharu 14' and 'Sumai 3' to
      determine their reaction to FHB during two seasons under field conditions. The DH
      lines were genotyped at five known FHB-resistance QTL regions (on chromosomes
      3BS, 5AS, 6BS, 2DL and 4BS) by using SSR markers. 'Sumai 3' alleles at the QTLs
      at 3BS and 5AS effectively reduced FHB damage in the environment of Hokkaido,
      indicating that these QTLs will be useful for breeding spring wheat cultivars
      suitable for Hokkaido. Some of the QTL regions influenced agronomic traits:
      'Sumai 3' alleles at the 4BS and 5AS QTLs significantly increased stem length and
      spike length, that at the 2DL QTL significantly decreased grain weight, and that
      at the 6BS QTL significantly delayed heading, indicating pleiotropic or linkage
      effects between these agronomic traits and FHB resistance.

PMID- 23136510
TI  - Characterization of near-isogenic lines carrying QTL for high spikelet number
      with the genetic background of an indica rice variety IR64 (Oryza sativa L.).
AB  - Total spikelet number per panicle (TSN) is one of the most important traits
      associated with rice yield potential. This trait was assessed in a set of 334
      chromosomal segment introgression lines (ILs: BC(3)-derived lines), developed
      from new plant type (NPT) varieties as donor parents and having the genetic
      background of an indica-type rice variety IR64. Among the 334 ILs, five lines
      which had different donor parents and showed significantly higher TSN than IR64
      were used for genetic analysis. Quantitative trait locus (QTL) analysis was
      conducted using F(2) populations derived from crosses between IR64 and these ILs.
      As a result, a QTL for high TSN (one from each NPT donor variety) was detected on
      common region of the long arm of chromosome 4. The effect of the QTL was
      confirmed by an increase in TSN of five near-isogenic lines (NILs) developed in
      the present study. The variation in TSN was found among these NILs, attributing
      to the panicle architecture in the numbers of primary, secondary and tertiary
      branches. The NILs for TSN and the SSR markers linked to the TSN QTLs are
      expected to be useful materials for research and breeding to enhance the yield
      potential of rice varieties.

PMID- 23136511
TI  - Genetic characterization of rainfed upland New Rice for Africa (NERICA)
      varieties.
AB  - A total of 18 rainfed upland New Rice for Africa (NERICA) varieties were
      categorized as the heavy panicle and low tillering types and early heading, in
      compared with 32 different varieties. These chromosome components were clarified
      using 243 SSR markers which showed polymorphism among NERICA varieties and their
      parents, CG 14 (O. glaberrima Steud.) and one of the recurrent parents, WAB-56
      104 (O. sativa L.). NERICA varieties were classified into three groups, which
      corresponded with these parents' continuation including two exceptions, NERICAs
      14 and 17, by a cluster analysis using polymorphism data of SSR markers and 14
      differential markers among them were selected to classify NERICA varieties.
      However, three groups: NERICAs, 3 and 4, NERICAs, 8, 9 and 11 and NERICAs, 15 and
      16 were not distinguishable. Association analysis was carried out for
      characterization of NERICA varieties by using SSR markers genotype and phenotype
      of agronomic traits. A total of 131 quantitative trait loci between SSR markers
      and 11 agronomic traits were detected. The characteristics of early maturity and
      heavy panicle of upland NERICA varieties were succeeded from Asian rice varieties
      and the characteristics of high dry matter production and late heading were
      introduced from CG 14 and the other varieties.

PMID- 23136512
TI  - Development of diversity array technology (DArT) markers for assessment of
      population structure and diversity in Aegilops tauschii.
AB  - Aegilops tauschii Coss. is the D-genome donor to hexaploid bread wheat (Triticum
      aestivum) and is the most promising wild species as a genetic resource for wheat
      breeding. To study the population structure and diversity of 81 Ae. tauschii
      accessions collected from various regions of its geographical distribution, the
      genomic representation of these lines were used to develop a diversity array
      technology (DArT) marker array. This Ae. tauschii array and a previously
      developed DArT wheat array were used to scan the genomes of the 81 accessions.
      Out of 7500 markers (5500 wheat and 2000 Ae. tauschii), 4449 were polymorphic
      (3776 wheat and 673 Ae. tauschii). Phylogenetic and population structure studies
      revealed that the accessions could be divided into three groups. The two Ae.
      tauschii subspecies could also be separately clustered, suggesting that the
      current taxonomy might be valid. DArT markers are effective to detect very small
      polymorphisms. The information obtained about Ae. tauschii in the current study
      could be useful for wheat breeding. In addition, the new DArT array from this Ae.
      tauschii population is expected to be an effective tool for hexaploid wheat
      studies.

PMID- 23136513
TI  - Distribution of MdACS3 null alleles in apple (Malus * domestica Borkh.) and its
      relevance to the fruit ripening characters.
AB  - Expression of MdACS3a, one of the ripening-related ACC synthase genes, plays a
      pivotal role in initiating the burst of ethylene production by MdACS1 in apple
      fruit. Although previous studies have demonstrated the presence of MdACS3a-null
      alleles through deficiency of transcription activity or loss of enzyme activity
      due to amino acid substitution, which may affect the storage properties of
      certain fruit cultivars, an overall picture of these null alleles in cultivars is
      still lacking. The present study investigated the distribution of null allelic
      genes in 103 cultivars and 172 breeding selections by using a simple sequence
      repeat (SSR) marker linked to them. The results indicated that both allelic genes
      were widely distributed throughout the examined cultivars and selections, some
      occurring as the null genotype, either homozygously or heterozygously, with each
      null allele. The implications of MdACS3a distribution results and the influence
      of its null allelotypes in fruit characters are discussed.

PMID- 23136514
TI  - Development of cultivar-specific DNA markers based on retrotransposon-based
      insertional polymorphism in Japanese pear.
AB  - We developed retrotransposon-based insertional polymorphism (RBIP) markers based
      on the long terminal repeat (LTR) sequences of copia-like retrotransposon Ppcrt4
      and flanking genome sequences, which were derived from 454 sequencing data from
      Japanese pear (Pyrus pyrifolia) 'Hosui'. Out of 40 sequences including both LTR
      and flanking genome regions, we developed 22 RBIP markers and used them for DNA
      profiling of 80 pear cultivars: 64 Japanese, 10 Chinese (Pyrus ussuriensis) and 6
      European (Pyrus communis). Three RBIP markers were enough to differentiate
      'Hosui' from the other Japanese pear cultivars. The 22 RBIP markers could also
      distinguish 61 of the 64 Japanese pear cultivars. European pears showed almost no
      amplification of the 22 RBIP markers, which might suggest that retrotransposons
      had transposed during Asian pear evolution or reflect the genetic relationship
      between Asian and European pears. Sixteen of the RBIP markers could be positioned
      on a genetic linkage map of 'Hosui'. The RBIP loci were distributed in 10 linkage
      groups, and some loci were very closely located within the same linkage group.
      The information obtained will be applicable to developing cultivar-specific RBIP
      marker sets in plants.

PMID- 23136515
TI  - Small variation of glucosinolate composition in Japanese cultivars of radish
      (Raphanus sativus L.) requires simple quantitative analysis for breeding of
      glucosinolate component.
AB  - To reveal varietally differing glucosinolate (GSL) contents in radish (Raphanus
      sativus L.) cultivated in Japan, the total and individual GSLs of 28 cultivars
      were analyzed using high-performance liquid chromatography. In these cultivars,
      GSL types including three aliphatic GSLs (glucoraphenin, glucoerucin, and 4
      methylthio-3-butenyl GSL (4MTB-GSL)) and three indolyl GSLs (4
      hydroxyglucobrassicin, glucobrassicin, and 4-methoxy-glucobrassicin) were
      detected. No cultivar-specific type of GSL was identified. The dominant GSL was
      4MTB-GSL, but its contents differed remarkably: 8.6 MUmol/g in 'Koushin' to 135.7
      MUmol/g in 'Karami 199'. Over about 90% of all GSLs in Japanese radish type are
      4MTB-GSL, a higher percentage than in Chinese or European garden radish
      cultivars. A simple, rapid method for estimating total GSL contents in crude
      extracts was established because of the small variation of glucosinolate
      composition in Japanese cultivars. The total GSL content can be estimated using
      an equation for prediction with absorbance at 425 nm in a mixture of GSL crude
      extract and palladium (II) chloride solution: Total GSL (MUmol/g) = 305.47 *
      A(425) - 29.66. Its coefficient of determination (R(2)) and standard error of
      prediction (SEP) are 0.968 and 8.052. This method enables total GSL content
      estimation from more than 200 samples per person per day.

PMID- 23136516
TI  - Comparison of physiological and yield traits between purple- and white-pericarp
      rice using SLs.
AB  - Five physiological and eleven yield traits of two pairs of sister lines generated
      from a high generation with similar genetic background (SLs) for purple pericarp
      were investigated to explore the reasons behind low-yield production of colored
      rice. Of the five physiological traits examined, except grain anthocyanin
      content, there were generally similar trends between the P (purple-pericarp)
      lines and the corresponding W (white-pericarp) lines over two seasons (in the
      year 2009 and 2010 separately). The results demonstrated that the chlorophyll
      content of flag leaves, the net photosynthetic rate of flag leaves, and the grain
      anthocyanin content could be easily influenced by the environment. The
      physiological functions of the traits for the P lines were more active than those
      of the corresponding W lines in the year 2010. The grain anthocyanin content of
      the P lines was much greater in the year 2010 than in the year 2009 during the
      growth period. The investigation of yield traits revealed that the P lines had
      reduced 1000-grain weight, yield per plot and grain/brown rice thickness compared
      to the W lines. A difference comparison of these traits and a source-sink and
      transportation relationship analysis for these SLs suggested that small sink size
      was a key reason behind yield reduction of purple pericarp rice.

PMID- 23136517
TI  - Identification of osmotic stress-responsive genes from Leymus mollis, a wild
      relative of wheat (Triticum aestivum L.).
AB  - The tolerance of the dune grass Leymus mollis (Triticeae; Poaceae) to various
      biotic and abiotic stresses makes it a very useful genetic resource for wheat
      breeding. Wide hybridization between L. mollis and wheat allows the introduction
      of Leymus chromosomes into the wheat genetic background and facilitates the
      integration of useful traits into wheat. However, the genetic basis controlling
      the physiological tolerance of L. mollis to multiple environmental stresses
      remains largely unexplored. Using suppression subtractive hybridization, we
      identified 112 osmotic-stress-responsive genes from L. mollis and confirmed their
      differential expression under osmotic stress. These genes were categorized into
      13 functional categories, including cell defense and stress response,
      transcriptional regulation, signal transduction, biosynthesis of compatible
      solutes and cell wall metabolism. Representative genes were validated by northern
      blot and RT-PCR analyses of expression patterns in response to osmotic stress and
      abscisic acid treatment. The genes identified here represent a useful source of
      expressed sequence tags (ESTs) for the analysis and identification of Leymus
      chromosomes introduced into wheat. Furthermore, being highly conserved,
      genetically associated with osmotic stress tolerance and transferable to wheat,
      these ESTs provide significant tools for the development of EST-derived molecular
      markers for introgression of osmotic stress tolerance genes into wheat.

PMID- 23136518
TI  - Mapping of quantitative trait loci for phytic acid and phosphorus contents in
      seed and seedling of mungbean (Vigna radiata (L.) Wilczek).
AB  - Phytic acid (PA) is the storage form of phosphorus (P) in seeds and plays an
      important role in the nutritional quality of food crops. There is little
      information on the genetics of seed and seedling PA in mungbean [Vigna radiata
      (L.) Wilczek]. Quantitative trait loci (QTL) were identified for phytic acid P
      (PAP), total P (TP), and inorganic P (IP) in mungbean seeds and seedlings, and
      for flowering, maturity and seed weight, in an F(2) population developed from a
      cross between low PAP cultivated mungbean (V1725BG) and high PAP wild mungbean
      (AusTRCF321925). Seven QTLs were detected for P compounds in seed; two for PAP,
      four for IP and one for TP. Six QTLs were identified for P compounds in seedling;
      three for PAP, two for TP and one for IP. Only one QTL co-localized between P
      compounds in seed and seedling suggesting that low PAP seed and low PAP seedling
      must be selected for at different QTLs. Seed PAP and TP were positively
      correlated with days to flowering and maturity, indicating the importance of
      plant phenology to seed P content.

PMID- 23136519
TI  - An SSR-based genetic map of pepper (Capsicum annuum L.) serves as an anchor for
      the alignment of major pepper maps.
AB  - Of the Capsicum peppers (Capsicum spp.), cultivated C. annuum is the most
      commercially important, but has lacked an intraspecific linkage map based on
      sequence-specific PCR markers in accord with haploid chromosome numbers. We
      constructed a linkage map of pepper using a doubled haploid (DH) population
      derived from a cross between two C. annuum genotypes, a bell-type cultivar
      'California Wonder' and a Malaysian small-fruited cultivar 'LS2341 (JP187992)',
      which is used as a source of resistance to bacterial wilt (Ralstonia
      solanacearum). A set of 253 markers (151 SSRs, 90 AFLPs, 10 CAPSs and 2 sequence
      tagged sites) was on the map which we constructed, spanning 1,336 cM. This is the
      first SSR-based map to consist of 12 linkage groups, corresponding to the haploid
      chromosome number in an intraspecific cross of C. annuum. As this map has a lot
      of PCR-based anchor markers, it is easy to compare it to other pepper genetic
      maps. Therefore, this map and the newly developed markers will be useful for
      cultivated C. annuum breeding.

PMID- 23136520
TI  - Development of EST-SSR markers of Ipomoea nil.
AB  - Although Japanese morning glory (Ipomoea nil (L.) Roth.) has been used
      intensively for genetic studies, DNA markers have not been developed in Ipomoea
      nil sufficient to cover all chromosomes. Therefore, we conducted microsatellite
      (simple sequence repeats, SSR) marker development in I. nil for future genetic
      studies. From 92,662 expressed sequence tag (EST) sequences, 514 unique
      microsatellite-containing ESTs were identified. Primer pairs were designed
      automatically in 326 SSRs. Of 150 SSRs examined, 75 showed polymorphisms among
      strains. A phenogram based on the SSR genotypes revealed the genetic relation
      among seven Japanese morning glories from five different regions of the world and
      an ivyleaf morning glory (I. hederacea Jacq.). The developed SSR markers might be
      applicable for genetic studies of morning glories and their relatives.

PMID- 23136521
TI  - Development and bioassay of transgenic Chinese cabbage expressing potato
      proteinase inhibitor II gene.
AB  - Lepidopteran larvae are the most injurious pests of Chinese cabbage production.
      We attempted the development of transgenic Chinese cabbage expressing the potato
      proteinase inhibitor II gene (pinII) and bioassayed the pest-repelling ability of
      these transgenic plants. Cotyledons with petioles from aseptic seedlings were
      used as explants for Agrobacterium-mediated in vitro transformation.
      Agrobacterium tumefaciens C58 contained the binary vector pBBBasta-pinII-bar
      comprising pinII and bar genes. Plants showing vigorous PPT resistance were
      obtained by a series concentration selection for PPT resistance and subsequent
      regeneration of leaf explants dissected from the putative chimera. Transgenic
      plants were confirmed by PCR and genomic Southern blotting, which showed that the
      bar and pinII genes were integrated into the plant genome. Double haploid
      homozygous transgenic plants were obtained by microspore culture. The pinII
      expression was detected using quantitative real time polymerase chain reaction
      (qRT-PCR) and detection of PINII protein content in the transgenic homozygous
      lines. Insect-feeding trials using the larvae of cabbage worm (Pieris rapae) and
      the larvae of the diamondback moth (Plutella xylostella) showed higher larval
      mortality, stunted larval development, and lower pupal weights, pupation rates,
      and eclosion rates in most of the transgenic lines in comparison with the
      corresponding values in the non-transformed wild-type line.

PMID- 23136522
TI  - Inter-sectional hybrids obtained from reciprocal crosses between Begonia
      semperflorens (section Begonia) and B. 'Orange Rubra' (section Gaerdita * section
      Pritzelia).
AB  - Inter-sectional hybrids were successfully obtained by the reciprocal crosses
      between 11 cultivars (including 6 diploids and 5 tetraploids) of Begonia
      semperflorens (SS & SSSS genomes) and B. 'Orange Rubra' (RR genome) with the aid
      of in vitro culture of mature or immature seeds on MS medium containing 0.1 mg l(
      1) alpha-naphthylacetic acid, 0.1 mg l(-1) 6-benzyladenine, 10 mg l(-1)
      gibberellic acid, 30 g l(-1) sucrose and 2.5 g l(-1) gellan gum. Embryo rescue as
      ovary culture with immature seeds 12(th)-16(th) day after pollination (DAP)
      generally gave higher efficiency of plantlet formation, but in some cross
      combinations, culture of mature seeds (30 DAP) resulted in higher yield of
      plantlets. Flow cytometric analysis revealed that they were consisted of the
      plants with various genomic combinations (RS, RR, RSS, RRS, RRSS and RRRRSS) as
      estimated by the DNA contents of both parents. Hybridity of these plants with
      various genomic combinations including RR was confirmed by random amplified
      polymorphic DNA analysis. These results suggested that unreduced gamete formation
      and spontaneous chromosome doubling were involved in the hybrid formation of
      various ploidy levels and genomic combinations. These hybrids showed various
      levels of intermediate traits between both parents according to the genomic
      compositions, and some of them had desirable characters of both parents.

PMID- 23136523
TI  - Agronomic traits and gene containment capability of cleistogamous rice lines with
      the superwoman1-cleistogamy mutation.
AB  - Pollen-mediated transgene flow is a major concern for the production of
      genetically modified (GM) rice. Cleistogamy is a useful tool for preventing this
      form of gene flow. We previously identified the cleistogamous rice mutant
      superwoman1-cleistogamy (spw1-cls) and determined its molecular genetic
      mechanism. In the present study, we cultivated spw1-cls over five years to
      examine effects of cleistogamy on agronomic traits. Simultaneously, we cultivated
      cleistogamous backcross lines created by continuous backcrossing with "Yumeaoba"
      (a japonica cultivar) as the recurrent parent and by application of a DNA marker.
      In these experimental cultivations, spw1-cls and its backcross lines showed
      almost equal or slightly lower, but acceptable, agronomic traits compared with
      each control line. We also conducted natural crossing tests in paddy fields to
      assess the gene containment capability of spw1-cls. In a series of field
      experiments, there was no natural crossing between spw1-cls (pollen donor) and
      pollen recipient lines, but the wild-type donor and recipient lines were crossed.
      Thus, the cleistogamy of the spw1-cls mutation is able to inhibit natural
      crossing effectively, without significant loss of commercial benefits, such as
      yield. We conclude that spw1-cls cleistogamy is a practical tool for gene
      containment in GM rice cultivation.

PMID- 23136524
TI  - An atypical bHLH protein encoded by POSITIVE REGULATOR OF GRAIN LENGTH 2 is
      involved in controlling grain length and weight of rice through interaction with
      a typical bHLH protein APG.
AB  - Grain size is an important yield component in rice, however, genes controlling
      the trait remain poorly understood. Previously, we have shown that an
      antagonistic pair of basic helix-loop-helix (bHLH) proteins, POSITIVE REGULATOR
      OF GRAIN LENGTH 1 (PGL1) and ANTAGONIST OF PGL1 (APG), is involved in controlling
      rice grain length. Here, we report the involvement of another atypical bHLH
      protein gene, POSITIVE REGULATOR OF GRAIN LENGTH 2 (PGL2), in the regulation of
      rice grain length. Over-expression of PGL2 in the lemma/palea increased grain
      length and weight in correlation with the level of transgene expression.
      Observation of the inner epidermal cells of lemma of PGL2-overexpressing lines
      revealed that the long grain size is caused by an increase in cell length. PGL2
      interacts with a typical bHLH protein APG, a negative regulator of rice grain
      length and weight, in vitro and in vivo. It was reported that overexpression of
      BU1 (BRASSINOSTEROID UPREGULATED 1), the closest homolog of PGL2, caused an
      increase in grain length. However, we detected no interaction between BU1 and
      APG. These findings suggest that PGL2 and PGL1 redundantly suppress the function
      of APG by forming heterodimers to positively regulate the rice grain length,
      while the pathway through which BU1, the closest homolog of PGL2, controls grain
      length is independent of APG.

PMID- 23136525
TI  - DNA marker-assisted evaluation of potato genotypes for potential resistance to
      potato cyst nematode pathotypes not yet invading into Japan.
AB  - One of major objectives of crop breeding is conferring resistance to diseases and
      pests. However, large-scale phenotypic evaluation for many diseases and pests is
      difficult because strict controls are required to prevent their spread. Detection
      of disease resistance genes by using DNA markers may be an alternative approach
      to select potentially resistant accessions. Potato (Solanum tuberosum L.)
      breeders in Japan extensively use resistance gene H1, which confers nearly
      absolute resistance to potato cyst nematode (Globodera rostochiensis) pathotype
      Ro1, the only pathotype found in Japan. However, considering the possibility of
      accidental introduction of the other pathotypes, breeding of resistant varieties
      is an important strategy to prevent infestation by non-invading pathotypes in
      Japan. In this study, to evaluate the prevalence of resistance genes in Japanese
      genetic resources, we developed a multiplex PCR method that simultaneously
      detects 3 resistance genes, H1, Gpa2 and Gro1-4. We revealed that many Japanese
      varieties possess not only H1 but Gpa2, which are potentially resistant to other
      pathotypes of potato cyst nematode. On the other hand, no genotype was found to
      have the Gro1-4, indicating importance of introduction of varieties having Gro1
      4. Our results demonstrate the applicability of DNA-marker assisted evaluation of
      resistant potato genotypes without phenotypic evaluation.

PMID- 23136526
TI  - Mapping of QTLs underlying flowering time in sorghum [Sorghum bicolor (L.)
      Moench].
AB  - Due to its critical importance in crop yield, the photoperiodic regulation of
      flowering time is considered an important trait in sorghum breeding programs. In
      this study, quantitative trait loci for flowering time were detected using an
      F(2) population derived from a cross between Kikuchi Zairai, a late-flowering
      cultivar originating from Japan and SC112, an early-flowering cultivar
      originating from Ethiopia. F(2) plants were grown with their parents under a
      natural day length and a 12 h day length. Two linkage maps were constructed using
      213 simple sequence repeats markers. Nine quantitative trait loci controlling
      flowering time were identified in F(2) plants grown under a natural day length,
      whereas 7 QTLs were identified under a 12 h day length. Five QTLs controlling
      flowering time were shared under both of the day length conditions.

PMID- 23136527
TI  - Modes of inheritance of two apomixis components, diplospory and parthenogenesis,
      in Chinese chive (Allium ramosum) revealed by analysis of the segregating
      population generated by back-crossing between amphimictic and apomictic diploids.
AB  - To investigate the mode of inheritance of apomixis in Chinese chive, the degrees
      of diplospory and parthenogenesis were evaluated in F(1) and BC(1) progenies
      derived from crosses between amphimictic and apomictic diploids (2n = 16, 2x).
      The F(1) population was generated by crossing three amphimictic diploids 94Mo13,
      94Mo49 and 94Mo50 with an apomictic diploid KaD2 and comprised 110 diploids and
      773 triploids. All the diploid F(1) plants examined were completely or highly
      eusporous and completely syngamic. All the triploid F(1) plants examined were
      highly diplosporous and highly parthenogenetic. KaD2 could not transmit its high
      level of apomixis via monoploid pollen grains. The BC(1) population, generated by
      crossing 94Mo49 with apomictic triploids found in the F(1) offspring, exhibited
      heteroploidy; it comprised haploid, diploid, triploid, tetraploid and various
      aneuploid individuals. In this generation, clear segregation was observed between
      diplospory and parthenogenesis. Analysis of the BC(1) population suggests that
      diplospory and parthenogenesis are each controlled by single dominant genes, D
      and P, respectively. However, all the BC(1) plants characterized as
      parthenogenetic were diplosporous. The absence of phenotypically eusporous
      parthenogenetic plants can be explained by assuming that the presence of
      diplospory gene is a prerequisite for the parthenogenesis gene expression in
      Chinese chive.

PMID- 23136528
TI  - Microstructure of a Brassica rapa genome segment homoeologous to the resistance
      gene cluster on Arabidopsis chromosome 4.
AB  - Genome evolution is a continuous process and genomic rearrangement occurs both
      within and between species. With the sequencing of the Arabidopsis thaliana
      genome, comparative genetics and genomics offer new insights into plant biology.
      The genus Brassica offers excellent opportunities with which to compare genomic
      synteny so as to reveal genome evolution. During a previous genetic analysis of
      clubroot resistance in Brassica rapa, we identified a genetic region that is
      highly collinear with Arabidopsis chromosome 4. This region corresponds to a
      disease resistance gene cluster in the A. thaliana genome. Relying on synteny
      with Arabidopsis, we fine-mapped the region and found that the location and order
      of the markers showed good correspondence with those in Arabidopsis. Microsynteny
      on a physical map indicated an almost parallel correspondence, with a few
      rearrangements such as inversions and insertions. The results show that this
      genomic region of Brassica is conserved extensively with that of Arabidopsis and
      has potential as a disease resistance gene cluster, although the genera diverged
      20 million years ago.

PMID- 23136529
TI  - Two novel QTLs regulate internode elongation in deepwater rice during the early
      vegetative stage.
AB  - Deepwater rice possesses internode elongation ability to avoid drowning under
      deepwater conditions. Previous studies identified three QTLs regulating internode
      elongation ability on chromosomes 1, 3 and 12 using different populations.
      However, these QTLs only induce internode elongation in response to deepwater
      conditions from the 7-leaf stage and not during the early leaf stage. In this
      study, we detected two novel QTLs, qTIL2 and qTIL4 regulating deepwater response
      at the early leaf stage using an F(2) population derived from the cross between
      NIL1-3-12 carrying the three QTLs regulating deepwater response in T65 (O. sativa
      ssp. japonica) genetic background and C9285 (O. sativa ssp. indica, deepwater
      rice). Plants of the BC(2)F(2) population derived from NIL1-3-12/C9285 and the
      RILs of T65/Bhadua (O. sativa ssp. indica, deepwater rice) possessing these QTLs
      as well as the three QTLs previously identified also showed internode elongation
      during the early leaf stage. These results indicate that qTIL2 and qTIL4 regulate
      early internode elongation and function in coordination with the three major QTLs
      under deepwater conditions. The results presented here would not only help define
      the mechanism of deepwater response in rice but also contribute in the breeding
      of deepwater tolerant rice that is adapted to various water depths.

PMID- 23136530
TI  - Expressed sequence tags from organ-specific cDNA libraries of tea (Camellia
      sinensis) and polymorphisms and transferability of EST-SSRs across Camellia
      species.
AB  - Tea is one of the most popular beverages in the world and the tea plant, Camellia
      sinensis (L.) O. Kuntze, is an important crop in many countries. To increase the
      amount of genomic information available for C. sinensis, we constructed seven
      cDNA libraries from various organs and used these to generate expressed sequence
      tags (ESTs). A total of 17,458 ESTs were generated and assembled into 5,262
      unigenes. About 50% of the unigenes were assigned annotations by Gene Ontology.
      Some were homologous to genes involved in important biological processes, such as
      nitrogen assimilation, aluminum response, and biosynthesis of caffeine and
      catechins. Digital northern analysis showed that 67 unigenes were expressed
      differentially among the seven organs. Simple sequence repeat (SSR) motif
      searches among the unigenes identified 1,835 unigenes (34.9%) harboring SSR
      motifs of more than six repeat units. A subset of 100 EST-SSR primer sets was
      tested for amplification and polymorphism in 16 tea accessions. Seventy-one
      primer sets successfully amplified EST-SSRs and 70 EST-SSR loci were polymorphic.
      Furthermore, these 70 EST-SSR markers were transferable to 14 other Camellia
      species. The ESTs and EST-SSR markers will enhance the study of important traits
      and the molecular genetics of tea plants and other Camellia species.

PMID- 23136531
TI  - Characterization and identification of cold tolerant near-isogenic lines in rice.
AB  - To exploit the genetic mechanism of cold tolerance in rice, cold tolerant near
      isogenic lines (NILs) were developed by backcrossing Kunmingxiaobaigu (KMXBG),
      reported to be the most cold-tolerant variety at the booting stage, as donor,
      with the cold sensitive Japanese commercial japonica variety, Towada. Comparisons
      of cold tolerance-related traits between five BC(6)F(5) NILs and recurrent parent
      Towada under cold treatment and normal temperatures at the booting stage showed
      that the differences between the NILs and Towada were significant only for
      spikelet fertility-related traits. Analyses of cold tolerance in the NILs at the
      budding (germination), seedling and booting stages indicated both correlated
      effects and differences. Lines 1913-4 and 1916-1 showed strong and stable
      tolerance at all three stages. Whole genome marker screening showed that the
      proportion of genetic background recovery was more than 98%. Seventeen markers
      from KMXBG were introgressed in two or more NILs, and cold tolerance genes were
      possibly present in these marker regions. The NILs should be excellent materials
      for both rice improvement and map-based cloning of cold tolerance QTLs.

PMID- 23136532
TI  - Availability of Micro-Tom mutant library combined with TILLING in molecular
      breeding of tomato fruit shelf-life.
AB  - Novel mutant alleles of an ethylene receptor Solanum lycopersicum ETHYLENE
      RESPONSE1 (SlETR1) gene, Sletr1-1 and Sletr1-2, were isolated from the Micro-Tom
      mutant library by TILLING in our previous study. They displayed different levels
      of impaired fruit ripening phenotype, suggesting that these alleles could be a
      valuable breeding material for improving shelf life of tomato fruit. To conduct
      practical use of the Sletr1 alleles in tomato breeding, genetic complementation
      analysis by transformation of genes carrying each allele is required. In this
      study, we generated and characterized transgenic lines over-expressing Sletr1-1
      and Sletr1-2. All transgenic lines displayed ethylene insensitive phenotype and
      ripening inhibition, indicating that Sletr1-1 and Sletr1-2 associate with the
      ethylene insensitive phenotype. The level of ethylene sensitivity in the seedling
      was different between Sletr1-1 and Sletr1-2 transgenic lines, whereas no apparent
      difference was observed in fruit ripening phenotype. These results suggested that
      it is difficult to fine-tune the extent of ripening by transgenic approach even
      if the weaker allele (Sletr1-2) was used. Our present and previous studies
      indicate that the Micro-Tom mutant library combined with TILLING could be an
      efficient tool for exploring genetic variations of important agronomic traits in
      tomato breeding.

PMID- 23136533
TI  - What is the NHS Safety Thermometer?
AB  - The English National Health Service (NHS) announced a new programme to
      incentivize use of the NHS Safety Thermometer (NHS ST) in the NHS Operating
      Framework for 2012/13. For the first time, the NHS is using the Commissioning for
      Quality and Innovation (CQUIN) scheme, a contract lever, to incentivize ALL
      providers of NHS care to measure four common complications (harms) using the NHS
      ST in a proactive way on one day per month. This national CQUIN scheme provides
      financial reward for the collection of baseline data with a view to incentivizing
      the achievement of improvement goals in later years. In this paper, we describe
      the rationale for this large-scale data collection, the purpose of the instrument
      and its potential contribution to our current understanding of patient safety. It
      is not a comprehensive description of the method or preliminary data. This will
      be published separately. The focus of the NHS ST on pressure ulcers, falls,
      catheters and urine infection and venous thromboembolism is broadly applicable to
      patients across all healthcare settings, but is specifically pertinent to older
      people who, experiencing more healthcare intervention, are at risk of not one but
      multiple harms. In this paper, we also describe an innovative patient-level
      composite measure of the absence of harm from the four identified, termed as
      "harmfreecare" which is unique to the NHS ST and is under development to raise
      standards for patient safety.

PMID- 23136534
TI  - Synthesis of Neoglycoconjugates Containing 4-Amino-4-deoxy-l-arabinose Epitopes
      Corresponding to the Inner Core of Burkholderia and Proteus Lipopolysaccharides.
AB  - Disaccharides that contain 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) and d
      glycero-d-talo-oct-2-ulosonic acid (Ko) substituted at the 8-position by 4-amino
      4-deoxy-beta-l-arabinopyranosyl (Ara4N) residues have been prepared. Coupling an
      N-phenyltrifluoroacetimidate-4-azido-4-deoxy-l-arabinosylglycosyl donor to acetyl
      protected allyl glycosides of Kdo and Ko afforded anomeric mixtures of
      disaccharide products in 74 and 90 % yield, respectively, which were separated by
      chromatography. Further extension of an intermediate Ara4N-(1->8)-Kdo
      disaccharide acceptor, which capitalized on a regioselective glycosylation with a
      Kdo bromide donor under Helferich conditions, afforded the branched trisaccharide
      alpha-Kdo-(2->4)[beta-l-Ara4N-(1->8)]-alpha-Kdo derivative. Deprotection of the
      protected di- and trisaccharide allyl glycosides was accomplished by TiCl(4)
      promoted benzyl ether cleavage followed by the removal of ester groups and
      reduction of the azido group with thiol or Staudinger reagents, respectively. The
      reaction of the anomeric allyl group with 1,3-propanedithiol under radical
      conditions afforded the thioether-bridged spacer glycosides, which were
      efficiently coupled to maleimide-activated bovine serum albumin. The
      neoglycoconjugates serve as immunoreagents with specificity for inner core
      epitopes of Burkholderia and Proteus lipopolysaccharides.

PMID- 23136535
TI  - Clinical efficacy of cervical length and volume for prediction of labor onset in
      VBAC candidates.
AB  - BACKGROUND: The purpose of this research is to discover whether measurement of
      cervical length and cervical volume at term is helpful in predicting the onset of
      labor in VBAC candidates. METHODS: Transvaginal sonographic evaluations of the
      cervixes of pregnant women who desired to undergo VBAC were performed between 36 
      40 weeks gestation. Clinical information such as labor onset time, gestational
      age at delivery and delivery mode was gathered from medical records. RESULTS: A
      total of 514 pregnant women participated in this study. Cervical length was
      significantly longer in the group that delivered 7 days or more after measurement
      than in the group that delivered within 7 days of measurement (43+/-0.77 cm vs.
      2.99+/-0.72 cm, p< 0.001). Cervical volume was significantly larger in the group
      that delivered at and after 7 days than in the group that delivered within 7 days
      (29.21+/-11.62 cm(3) vs. 34.07+/-13.41 cm(3), p=0.014). The cervical length ROC
      curve was significantly more predictive than the cervical volume ROC curve (AUC:
      0.711 vs 0.594, p= 0.001). There were no significant differences between the
      combined cervical length/volume ROC curve and the cervical length ROC curve alone
      (p= 0.565). The AUC of the cervical length ROC curve to predict postterm
      pregnancy was 0.729. CONCLUSION: Measuring cervical length is helpful in
      predicting the onset of spontaneous labor within 7 days and posterm delivery in
      VBAC candidates.

PMID- 23136536
TI  - A two-step control of secondary splenic pedicles using ligasure during
      laparoscopic splenectomy.
AB  - OBJECTIVE: We modified the LigaSure vessel sealing into a two-step technique
      without using Endo-GIA stapler for the secondary splenic pedicle control in
      laparoscopic splenectomy (LS). This study evaluated the efficacy and safety
      outcomes of this technique. METHODS: Patients (n = 105) scheduled for elective LS
      were consecutively and prospectively enrolled, including 24 males and 81 females,
      with a mean age of 43.6 (range 11-75) years. Following the mobilization of the
      spleen, the splenic inflow was interrupted by applying a Hem-o-lock clip.
      LigaSure was used to seal and transect the secondary splenic pedicles adjacent to
      the pancreatic tail and subsequently in proximity to the spleen. RESULTS: Of 105
      patients, 103 patients (98.1%) underwent successful LS, whereas two patients
      (1.9%) required the conversion to laparotomy. The mean operative time was 100
      min, whilst the mean volume of blood loss was 500 mL. No clinically significant
      morbidities or mortality occurred following LS. An average of 8,000 RMB (range:
      6900 to 9000; 1 USD = 6.5 RMB) was saved by using this two-step technique.
      CONCLUSION: Secondary splenic pedicles can be successfully controlled in LS by
      using a two-step technique with the LigaSure vessel sealing system in an
      economically favorable way.

PMID- 23136537
TI  - THRB genetic polymorphisms can predict severe myelotoxicity after definitive
      chemoradiotherapy in patients with esophageal squamous cell carcinoma.
AB  - OBJECTIVE: Chemotherapy-related toxicities are difficult to predict before
      treatment. In this study, we investigated whether thyroid hormone receptor beta
      (THRB) genetic polymorphisms can serve as a potential biomarker in patients with
      esophageal squamous cell carcinoma (ESCC). METHODS: Forty-nine Japanese patients
      with ESCC who received a definitive chemoradiotherapy (CRT) with 5-fluorouracil
      and cisplatin in conjunction with concurrent irradiation were retrospectively
      analyzed. Severe acute toxicities, including leukopenia, stomatitis, and
      cheilitis, were evaluated according to 6 single nucleotide polymorphisms (SNPs)
      in the gene; the intronic SNPs of rs7635707 G/T, rs6787255 A/C, rs9812034 G/T,
      and rs9310738 C/T and the SNPs in the 3'-untranslated region (3'-UTR) of rs844107
      C/T and rs1349265 G/A. RESULTS: Distribution of the 4 intronic SNPs, but not the
      2 SNPs in the 3'-UTR, showed a significant difference between patients with and
      without severe acute leukopenia. Stomatitis and cheilitis were not associated
      with any of the 6 analyzed SNPs. Frequency of haplotype of the 4 intronic SNPs
      reached approximately 97% with the 2 major haplotypes G-A-G-C (73.4%) and T-C-T-T
      (23.5%). CONCLUSIONS: THRB intronic SNPs can provide useful information on CRT
      related severe myelotoxicity in patients with ESCC. Future studies will be needed
      to confirm these findings.

PMID- 23136538
TI  - Multiple-, but not single-, dose of parecoxib reduces shoulder pain after
      gynecologic laparoscopy.
AB  - BACKGROUND: The aim of this study was to investigate effect of single- and
      multiple-dose of parecoxib on shoulder pain after gynecologic laparoscopy.
      METHODS: 126 patients requiring elective gynecologic laparoscopy were randomly
      allocated to three groups. Group M (multiple-dose): receiving parecoxib 40mg at
      30min before the end of surgery, at 8 and 20hr after surgery, respectively; Group
      S (single-dose): receiving parecoxib 40mg at 30min before the end of surgery and
      normal saline at the corresponding time points; Group C (control): receiving
      normal saline at the same three time points. The shoulder pain was evaluated,
      both at rest and with motion, at postoperative 6, 24 and 48hr. The impact of
      shoulder pain on patients' recovery (activity, mood, walking and sleep) was also
      evaluated. Meanwhile, rescue analgesics and complications were recorded. RESULTS:
      The overall incidence of shoulder pain in group M (37.5%) was lower than that in
      group C (61.9%) (difference=-24.4%; 95% CI: 3.4~45.4%; P=0.023). Whereas, single
      dose regimen (61.0%) showed no significant reduction (difference with control=
      0.9%; 95% CI: -21.9~20.0%; P=0.931). Moreover, multiple-dose regimen reduced the
      maximal intensity of shoulder pain and the impact for activity and mood in
      comparison to the control. Multiple-dose of parecoxib decreased the consumption
      of rescue analgesics. The complications were similar among all groups and no
      severe complications were observed. CONCLUSIONS: Multiple-, but not single-, dose
      of parecoxib may attenuate the incidence and intensity of shoulder pain and
      thereby improve patients' quality of recovery following gynecologic laparoscopy.

PMID- 23136539
TI  - Non-stimulation needle with external indwelling cannula for brachial plexus block
      and pain management in 62 patients undergoing upper-limb surgery.
AB  - OBJECTIVE: To investigate the feasibility of a non-stimulation needle with an
      external indwelling cannula for upper-limb surgery and acute postoperative pain
      management. METHODS: 62 patients undergoing either scheduled or emergency upper
      limb surgery received brachial plexus block of modified interscalene or axillary
      brachial and then postoperative patient-controlled analgesia (PCA) with local
      analgesics using a specially designed non-stimulation needle with an external
      indwelling cannula. The outcome measurements included anesthetic effect, acute or
      chronic complications, postoperative analgesic effect and patient's satisfaction.
      RESULTS: The success rate of anesthesia was 96.8%. The single attempt placement
      with the external indwelling cannula was achieved in 85.2% of patients with
      axillary brachial plexus block and 78.8% with modified interscalene brachial
      plexus block. The incidence of severe intoxication was 3.7% with axillary
      brachial plexus block and 3.0% with modified interscalene brachial plexus block.
      No hematoma at the injection site, Horner's syndrome, hoarseness or dyspnea was
      observed. Postoperative analgesic effect was achieved in 100% and activities were
      slightly lowered in 91.7%. The incidence of nausea and vomit was 8.3%; patient's
      satisfaction was 9.1 on a 10-point scale system. Infection, nerve injury and
      respiratory depression were absent during the catheter indwelling. The indwelling
      time of external indwelling cannula was 30.5 h on average. There was no nerve
      injury related complication after withdrawing the external indwelling catheter.
      CONCLUSIONS: Brachial plexus block using a non-stimulation needle with an
      external indwelling cannula has favorable intra-operative anesthetic benefit and
      provides an excellent postoperative analgesic outcome. The low incidence of
      complications and favorable patient's satisfaction suggest that non-stimulation
      needle with an external indwelling cannula is a useful and safe anesthetic tool
      in brachial nerve block and acute postoperative pain management.

PMID- 23136540
TI  - Plasma brain-derived neurotrophic factor in hemodialysis patients.
AB  - OBJECTIVE: Brain-derived neurotrophic factor (BDNF) is a neurotrophin which
      modulates neuronal survival and proliferation. Recently, plasma BDNF is
      associated with inflammatory conditions. The present study was to investigate the
      changes of the plasma BDNF level in hemodialysis patients and to evaluate the
      relationship between the plasma BDNF and uremic inflammation. METHOD: We measured
      the plasma BDNF, serum IL-2, IL-4, IFN-gamma and TNF-alpha in hemodialysis
      patients and control subjects. In addition, we investigated the associations of
      the plasma BDNF with clinical or biochemical parameters. RESULTS: The plasma BDNF
      level was significantly higher in hemodialysis patients than in the control
      subjects (median, 312.3 vs. 630.3 pg/ml, p < 0.05). In subgroup analysis,
      hemodialysis patients with diabetes showed higher values of the plasma BDNF than
      the patients without diabetes. However, there were no significant differences in
      age and gender subgroups of the hemodialysis patients. The logBDNF was positively
      correlated with hs-CRP and IFN-gamma, and negatively correlated with serum
      albumin. In multivariate regression analysis, the logBDNF was independently
      associated with the presence of diabetes (beta-coefficient = 0.399, p = 0.041)
      and IFN-gamma (beta-coefficient = 0.538, p = 0.003). CONCLUSION: The plasma BDNF
      may increase in hemodialysis patients, and more prominently in the patients with
      diabetes. Furthermore, the plasma BDNF might reflect inflammatory condition in
      hemodialysis patients.

PMID- 23136541
TI  - Peri-operative treatment of giant nodular goiter.
AB  - OBJECTIVE: To summarize the experience in the peri-operative treatment of giant
      nodular goiter. METHODS: A total of 123 patients with giant nodular goiter sized
      6~20 cm were admitted into our hospital from 1990 to 2011 and the clinical data
      were retrospectively analyzed. These patients underwent total or subtotal
      thyroidectomy. RESULTS: All patients underwent surgical intervention. Unilateral
      subtotal thyroidectomy was performed in 40 patients, unilateral total
      thyroidectomy in 1 patient, bilateral subtotal thyroidectomy in 79 patients, and
      unilateral total thyroidectomy, removal of entire isthmus and contralateral
      subtotal thyroidectomy in 3 patients. Nodular goiter was pathologically proven
      post-operatively. No short-term complications such as dyspnea or thyroid storm
      were found postoperatively. Post-operative follow up was done for 9 months to 6
      years and no recurrence was observed. CONCLUSION: Comprehensive pre-operative
      preparation, pre-operative evaluation, complete exposure of the operative field,
      meticulous operation, effective control and prevention of hemorrhage and
      prevention against damage to superior and recurrent laryngeal nerves are crucial
      for the successful surgical intervention of giant nodular goiter.

PMID- 23136542
TI  - Effects of smokeless tobacco "Maras powder" use on nitric oxide and
      cardiovascular risk parameters.
AB  - BACKGROUND: Smokeless tobacco use is common in various parts of the world. In
      Turkey a type of smokeless tobacco called "Maras powder" is widely used in
      southeastern region. Smoking is known to have an adverse effect on nitric oxide
      and cardiovascular risk factors. The aim of this study was to evaluate whether
      there is difference between the effects of Maras powder and cigarette smoking on
      the cardiovascular risk factors and nitric oxide levels. METHODS: In the study,
      participants were 48 Maras powder users, 50 cigarette smokers and 45 nontobacco
      user subjects. Blood samples were collected and hematological parameters and
      lipid parameters were measured. Plasma Nitric oxide level was also detected by
      using the Griess method. RESULTS: Plasma total cholesterol, LDL-cholesterol,
      triglyceride levels were significantly higher in Maras powder and cigarette
      smokers group than in the nontobacco user group (p<0.001). Plasma HDL-cholesterol
      levels were significantly lower in Maras powder and cigarette smokers group than
      in the nontobacco user group (p<0.001). Plasma Nitric oxide levels were found
      significantly lower in Maras powder and cigarette smokers group compared to the
      nontobacco user group (4.9+/-0.9 umol/l, 4.8+/-1 umol/l, 9.4+/-3.4 umol/l,
      respectively, p<0.001) whereas there was no significant difference between the
      Maras powder and cigarette smokers group. In multivariate logistic regression
      model, cigarette smoking (Odds ratio=17.832, p<0.001), Maras powder usage (Odds
      ratio=12.311, p=0.002) and mean platelet volume (Odds ratio=1.425, p=0.030)
      remained independently associated with lower Nitric oxide levels. CONCLUSION: We
      conclude that Maras powder has similar adverse effects on nitric oxide level and
      cardiovascular risk parameters and thereby it appears to be harmful as cigarette
      smoking.

PMID- 23136543
TI  - Synergistic effects of honey and propolis toward drug multi-resistant
      Staphylococcus aureus, Escherichia coli and Candida albicans isolates in single
      and polymicrobial cultures.
AB  - BACKGROUND: Propolis and honey are natural bee products with wide range of
      biological and medicinal properties. The study investigated antimicrobial
      activity of ethyl alcohol extraction of propolis collected from Saudi Arabia
      (EEPS) and from Egypt (EEPE), and their synergistic effect when used with honey.
      Single and polymicrobial cultures of antibiotic resistant human pathogens were
      tested. MATERIAL AND METHODS: Staphylococcus aureus (S. aureus),), Escherichia
      coli (E. coli) and Candida albicans (C.albicans) were cultured in 10-100% (v/v)
      honey diluted in broth, or 0.08-1.0% (weight/volume) EEPS and EEPE diluted in
      broth. Four types of polymicrobial cultures were prepared by culturing the
      isolates with each other in broth (control) and broth containing various
      concentrations of honey or propolis. Microbial growth was assessed on solid plate
      media after 24 h incubation. RESULTS: EEPS and EEPE inhibited antibiotic
      resistant E.coli, and S.aureus, and C.albicans in single and polymicrobial
      cultures. S.aureus became more susceptible when it was cultured with E.coli or
      C.albicans or when all cultured together. C.albicans became more susceptible when
      it was cultured with S.aureus or with E.coli and S. aureus together. The presence
      of ethyl alcohol or honey potentiated antimicrobial effect of propolis toward
      entire microbes tested in single or polymicrobial cultures. EEPS had lower MIC
      toward E.coli and C.albicans than EEPE. When propolis was mixed with honey, EEPS
      showed lower MIC than EEPE. In addition, honey showed lower MIC toward entire
      microbes when mixed with EEPS than when it was mixed with EEPE. CONCLUSION: 1)
      propolis prevents the growth of the microorganisms in single and mixed microbial
      cultures, and has synergistic effect when used with honey or ethyl alcohol, 2)
      the antimicrobial property of propolis varies with geographical origin, and 3)
      this study will pave the way to isolate active ingredients from honey and
      propolis to be further tested individually or in combination against human
      resistant infections.

PMID- 23136544
TI  - Low-magnitude high-frequency vibration inhibits RANKL-induced osteoclast
      differentiation of RAW264.7 cells.
AB  - Osteoclasts are the key participants in regulation of bone mass. Low-magnitude
      high-frequency vibration (LMHFV) has been found to be anabolic to bone in vivo.
      This study aimed to investigate the effect of LMHFV on osteoclast differentiation
      in vitro. Murine monocyte cell line RAW264.7 cells in the presence of receptor
      activator of nuclear factor-kappaB ligand (RANKL) were treated with or without
      LMHFV at 45 Hz (0.3 g) for 15 min day(-1). Tartrate resistant acid phosphatase
      (TRAP)-positive multinucleated cells (MNCs) and actin ring formation were
      evaluated. Expression of the osteoclast-specific genes, such as cathepsin K,
      matrix metallopeptidase-9 (MMP-9) and TRAP, were analyzed using real time-PCR. c
      Fos, an osteoclast-specific transcription factor, was determined using Western
      blot. We found that LMHFV significantly decreased the number of RANKL-induced
      TRAP-positive MNCs (P<0.01), and inhibited the actin ring formation. The mRNA
      expression of the cathepsin K, MMP-9 and TRAP were down-regulated by LMHFV
      intervention (all P<0.001). Furthermore, LMHFV also inhibited the expression of c
      Fos protein in the RANKL-treated RAW264.7 cells (P<0.05). Our results suggest
      that LMHFV can inhibit the RANKL-induced osteoclast differentiation of RAW264.7
      cells, which give some new insight into the anabolic effects of LMHFV on bone.

PMID- 23136545
TI  - How the duration period of erythropoietin treatment influences the oxidative
      status of hemodialysis patients.
AB  - BACKGROUND: End-stage renal disease is a state of enhanced oxidative stress (OS)
      and hemodialysis (HD) and renal anemia further augment this disbalance. Anemia
      correction with erythropoietin (EPO) may improve oxidative status. However, there
      is no evidence of time dependent effects of EPO therapy on redox status of HD
      patients. OBJECTIVE: The aim of this study was to evaluate whether the duration
      of EPO treatment may affect OS parameters in uremic patients. PATIENTS AND
      METHODS: 104 HD patients and 29 healthy volunteers were included. Patients were
      divided into 3 groups according to the duration of EPO treatment. Forth group
      consisted of HD patients without EPO treatment. Plasma and erythrocyte
      malondialdehyde (MDA, MDA(rbc)), reactive carbonyl groups (RCG), plasma
      sulfhydryl (-SH) groups and total antioxidative capacity (TAC) levels were
      evaluated. RESULTS: HD patients both with and without EPO treatment, showed a
      significant increase in all oxidative parameters without significance between EPO
      treated and -untreated group. The decrease in MDA and MDA(rbc) levels coincided
      with the duration of EPO treatment. A negative correlation was observed between
      the duration of EPO treatment and serum MDA (r=-0.309, p=0.003). Increasing
      periods of EPO treatment were associated with decrease in RCG, without
      significance between EPO groups. Increase in TAC accompanied increasing durations
      of EPO treatment, with EPO treatment for more than 24 months causing the most
      striking changes (p<0.05). There were no significant differences in -SH levels
      between EPO subgroups. CONCLUSION: Our results suggest that long term
      administration of EPO attenuated the lipid peroxidation process and restored the
      levels of antioxidants.

PMID- 23136546
TI  - Development of a clinically relevant animal model for the talar osteonecrosis in
      sheep.
AB  - There are a lot of reports and reviews about osteonecrosis of the talus (ONT),
      yet reports about the animal model of ONT to evaluate proper therapeutic
      approaches are rarely heard. In our study, a novel animal model was established.
      Pure ethanol was injected into the cancellous bone of sheep's talus. Macroscopic
      observation, X-ray, CT and histology were performed at two, four, 12 and 24 weeks
      postoperatively. It was revealed that the trabeculae of talar head began to
      change their structure after two weeks postoperatively compared to the normal
      talus. The ONT was obvious at the end of the fourth week, and their outstanding
      feature was the damage of trabeculae bone and formation of cavities. CT scans and
      pathological changes of the subjects all showed characteristics of the early
      stage of osteonecrosis, also the sections of the specimens confirmed necrosis of
      tali. By 12 weeks, the phenomenon of necrosis still existed but fibrous tissue
      proliferated prominently and bone reconstruction appeared in certain area. Most
      specimens (3/4) got late stage necrosis which presented as synarthrosis in X-ray
      and mass proliferation of fibrous tissue in histology at the end of 24 weeks. The
      novel animal model of ONT was successful, and it is inclined to deteriorate
      without any intervention. The study provides us a new way to evaluate various
      treatments on ONT in laboratory, which may eventually pave way to clinical
      applications.

PMID- 23136547
TI  - Immune regulation of osteoclast function in postmenopausal osteoporosis: a
      critical interdisciplinary perspective.
AB  - Extensive studies on cross talk between immune and skeletal systems in autoimmune
      diseases give rise to a new discipline of 'osteoimmunology', which explores the
      molecular regulation of osteoclasts by immune system. Postmenopausal osteoporosis
      is recognized as a cytokine driven disease, but the mechanism that how estrogen
      deficiency interplaying with cytokines to stimulate bone loss remains to be
      elucidated. Although the effect of individual cytokines on osteoclast formation
      is well characterized, the major challenge is to fit a multitude of redundant
      pathways and cytokines into a systemic model of postmenopausal osteoporosis. This
      review presents current findings and hypothesis to explain estrogen deficiency
      stimulated bone loss in a critical interdisciplinary perspective. To better
      understand the interaction between osteoclasts and immune system in
      postmenopausal osteoporosis, many of the lessons have been explored in animal
      models.

PMID- 23136548
TI  - Tube-like structures with co-expression of D2-40 and CD34: newly formed
      vasculatures?
AB  - BACKGROUND: A great number of in vitro and in vivo studies have suggested that
      many pathways or factors can stimulate angiogenesis and lymphangiogenesis, which
      facilitate tumor progression and metastasis. However, the morphological and
      immunohistochemical profile of newly formed vasculatures has not been elucidated,
      making it difficult to differentiate them from the pre-existing ones, and to
      identify their unique molecular profiles for diagnosis and therapeutic
      interventions. EXPERIMENTAL FINDINGS: As cytokeratin (CK)-19 is a well-recognized
      stem cell marker and CK-19-positive cells are frequently detected in the
      peripheral blood of patients with metastatic cancer, our recent studies have
      assessed the involvement of CK-19 in the formation of new vasculatures in primary
      colorectal cancer (CRC) tissues. Our studies showed that a subset of lymph node
      positive cases harbored some isolated normal epithelial structures with distinct
      CK-19 immunostaining within an otherwise CK-19-negative background. These
      structures are exclusively located within or adjacent to lymphoid follicles and
      are often surrounded by tube-like structures expressing lymphatic endothelial
      marker D2-40. Similar structures are more frequently seen at the junctions
      between pre-invasive and invasive CRC with the following features: (1). they
      consist of a single layer of endothelial cells that express both D2-40 and CD34,
      (2). their endothelial walls are often incomplete with disseminated cells
      protruding into the adjacent stroma, and (3). they are exclusively associated
      with disseminated CK-19-positive cells HYPOTHESIS: Based on these findings, we
      propose that these tube-like structures represent newly formed vasculatures,
      which are derived by the convergence of aberrant lymphocyte infiltration and
      tumor stem cells. Because of their close physical proximity, tumor stem cells
      within the epithelial and stromal components contribute equally and coordinately
      to the morphogenesis of new vasculatures, which constitutes the basis for the
      unique morphologic and immunohistochemical features of newly formed vasculatures.
      Our hypothesis appears to be applicable to all epithelium-derived cancers.

PMID- 23136549
TI  - Thyroid hormone regulation of adult intestinal stem cell development: mechanisms
      and evolutionary conservations.
AB  - The adult mammalian intestine has long been used as a model to study adult stem
      cell function and tissue renewal as the intestinal epithelium is constantly
      undergoing self-renewal throughout adult life. This is accomplished through the
      proliferation and subsequent differentiation of the adult stem cells located in
      the crypt. The development of this self-renewal system is, however, poorly
      understood. A number of studies suggest that the formation/maturation of the
      adult intestine is conserved in vertebrates and depends on endogenous thyroid
      hormone (T3). In amphibians such as Xenopus laevis, the process takes place
      during metamorphosis, which is totally dependent upon T3 and resembles
      postembryonic development in mammals when T3 levels are also high. During
      metamorphosis, the larval epithelial cells in the tadpole intestine undergo
      apoptosis and concurrently, adult epithelial stem/progenitor cells are formed de
      novo, which subsequently lead to the formation of a trough-crest axis of the
      epithelial fold in the frog, resembling the crypt-villus axis in the adult
      mammalian intestine. Here we will review some recent molecular and genetic
      studies that support the conservation of the development of the adult intestinal
      stem cells in vertebrates. We will discuss the mechanisms by which T3 regulates
      this process via its nuclear receptors.

PMID- 23136550
TI  - Special issue on interleukin-6 (IL-6).

PMID- 23136551
TI  - Targeting interleukin-6: all the way to treat autoimmune and inflammatory
      diseases.
AB  - Interleukin (IL)-6, a cytokine featuring redundancy and pleiotropic activity,
      contributes to host defense against acute environmental stress, while
      dysregulated persistent IL-6 production has been demonstrated to play a
      pathological role in various autoimmune and chronic inflammatory diseases.
      Targeting IL-6 is thus a rational approach to the treatment of these diseases.
      Indeed, clinical trials of tocilizumab, a humanized anti-IL-6 receptor antibody
      have verified its efficacy and tolerable safety for patients with rheumatoid
      arthritis, Castleman's disease and systemic juvenile idiopathic arthritis,
      resulting in approval of this innovative biologic for treatment of these
      diseases. Moreover, a considerable number of case reports and pilot studies of
      off-label use of tocilizumab point to the beneficial effects of tocilizumab for a
      variety of other phenotypically different autoimmune and chronic inflammatory
      diseases. Elucidation of the source of IL-6 and of mechanisms through which IL-6
      production is dysregulated can thus be expected to lead to clarification of the
      pathogenesis of various diseases.

PMID- 23136552
TI  - IL-6 trans-signaling via the soluble IL-6 receptor: importance for the pro
      inflammatory activities of IL-6.
AB  - Interleukin-6 (IL-6) is a cytokine with many activities. It has functions in the
      regulation of the immune system and the nervous system. Furthermore, IL-6 is
      involved in liver regeneration and in the metabolic control of the body. On
      target cells, IL-6 binds to an 80 kDa IL-6 receptor (IL-6R). The complex of IL-6
      and IL-6R associates with a second protein, gp130, which thereupon dimerizes and
      initiates intracellular signaling. Whereas gp130 is expressed on all cells, IL-6R
      is only present on few cells in the body including hepatocytes and some
      leukocytes. Cells, which do not express IL-6R cannot respond to the cytokine,
      since gp130 alone has no measurable affinity for IL-6. Interestingly, a soluble
      form of IL-6R (sIL-6R) comprising the extracellular portion of the receptor can
      bind IL-6 with a similar affinity as the membrane bound IL-6R. The complex of IL
      6 and sIL-6R can bind to gp130 on cells, which do not express the IL-6R, and
      which are unresponsive to IL-6. This process has been called trans-signaling.
      Here I will review published evidence that IL-6 trans-signaling is pro
      inflammatory whereas classic IL-6 signaling via the membrane bound IL-6R is
      needed for regenerative or anti-inflammatory activities of the cytokine.
      Furthermore, the detailed knowledge of IL-6 biology has important consequences
      for therapeutic strategies aimed at the blockade of the cytokine IL-6.

PMID- 23136553
TI  - Interleukin-6--a key regulator of colorectal cancer development.
AB  - Growing evidence proposes an important role for pro-inflammatory cytokines during
      tumor development. Several experimental and clinical studies have linked the
      pleiotropic cytokine interleukin-6 (IL-6) to the pathogenesis of sporadic and
      inflammation-associated colorectal cancer (CRC). Increased IL-6 expression has
      been related to advanced stage of disease and decreased survival in CRC patients.
      According to experimental studies, these effects are mediated through IL-6 trans
      signaling promoting tumor cell proliferation and inhibiting apoptosis through
      gp130 activation on tumor cells with subsequent signaling through Janus kinases
      (JAKs) and signal transducer and activator of transcription 3 (STAT3). During
      recent years, several therapeutics targeting the IL-6/STAT3 pathway have been
      developed and pose a promising strategy for the treatment of CRC. This review
      discusses the molecular mechanisms and possible therapeutic targets involved in
      IL-6 signaling in CRC.

PMID- 23136555
TI  - The pathological and physiological roles of IL-6 amplifier activation.
AB  - The NFkappaB-triggered positive feedback loop for IL-6 signaling in type 1
      collagen+ non-immune cells (IL-6 amplifier) was first discovered to be a
      synergistic signal that is activated following IL-17A and IL-6 stimulation in
      type 1 collagen+ non-immune cells. Subsequent disease models have shown that it
      can also be stimulated by the simultaneous activation of NFkappaB and STAT3,
      functions as a local chemokine inducer, and acts as a mechanism for local
      inflammation, particularly chronic ones like rheumatoid arthritis and a multiple
      sclerosis. Moreover, we have recently shown that hyper activation of the IL-6
      amplifier via regional neural activation establishes a gateway for immune cells
      including autoreactive T cells to pass the blood-brain barrier at dorsal vessels
      in 5(th) lumbar cord. Here we review how the IL-6 amplifier is activated by
      neural activation and the physiological relevance of the gateway to the central
      nervous system. Accumulating evidences continues to suggest that the IL-6
      amplifier offers a potential molecular mechanism for the relationship between
      neural activation and the development of inflammatory diseases, which could
      establish a new interdisciplinary field that fuses neurology and immunology.

PMID- 23136554
TI  - Interleukin-6, a major cytokine in the central nervous system.
AB  - Interleukin-6 (IL-6) is a cytokine originally identified almost 30 years ago as a
      B-cell differentiation factor, capable of inducing the maturation of B cells into
      antibody-producing cells. As with many other cytokines, it was soon realized that
      IL-6 was not a factor only involved in the immune response, but with many
      critical roles in major physiological systems including the nervous system. IL-6
      is now known to participate in neurogenesis (influencing both neurons and glial
      cells), and in the response of mature neurons and glial cells in normal
      conditions and following a wide arrange of injury models. In many respects, IL-6
      behaves in a neurotrophin-like fashion, and seemingly makes understandable why
      the cytokine family that it belongs to is known as neuropoietins. Its expression
      is affected in several of the main brain diseases, and animal models strongly
      suggest that IL-6 could have a role in the observed neuropathology and that
      therefore it is a clear target of strategic therapies.

PMID- 23136557
TI  - Family Behavior Therapy for Use in Child Welfare: Results of a Case Study
      Involving an Abused Woman Formally Diagnosed With Alcohol Dependence, Bipolar
      Disorder, and Several Anxiety Disorders.
AB  - The results of a multiple-baseline case study of family behavior therapy (FBT) is
      described in a woman formally diagnosed with alcohol dependence, bipolar
      disorder, generalized anxiety disorder, specific phobia, and panic disorder. She
      was referred to treatment from the local Department of Family Services for child
      neglect and domestic violence. After baseline measures were administered, the
      first phase of treatment involved home safety tours aimed at reducing home
      hazards and cleanliness. A second phase of treatment additionally targeted family
      relationships through communication skills training exercises, and a third phase
      involved administration of the remaining FBT components to assist in
      comprehensively addressing other problem areas. Results indicated most problem
      areas were substantially improved, but only after they were comprehensively
      targeted in therapy.

PMID- 23136556
TI  - Role of IL-6 in asthma and other inflammatory pulmonary diseases.
AB  - The incidence and severity of chronic lung diseases is growing and affects
      between 100 and 150 million people worldwide and is associated with a significant
      rate of mortality. Unfortunately, the initial cause that triggers most chronic
      lung diseases remains unknown and current available therapies only ameliorate,
      but do not cure the disease. Thus, there is a need for identification of new
      targets and development of novel therapies especially for those most severely
      affected. IL-6, like other inflammatory cytokines, has been shown to be elevated
      in different lung diseases, but it was considered a byproduct of ongoing
      inflammation in the lung. However, recent studies support a dissociation of IL-6
      from inflammation in the lung and suggest that this cytokine plays an active role
      in pathogenesis of asthma and, in all likelihood, COPD. IL-6 may therefore be a
      germane target for treatment of these and other chronic lung disease. Here, we
      provide an overview of the studies in mouse models and human patients that
      provide support for the involvement of IL-6 in lung diseases.

PMID- 23136558
TI  - Consumer Evaluation of Dual Focus Mutual Aid.
AB  - Double Trouble in Recovery (DTR) is a "dual focus," 12 step-based mutual aid
      program tailored to assist recovery from co-occurring substance use and
      psychiatric disorders. OBJECTIVE: To determine consumers' perceptions of DTR's
      usefulness for their recoveries and the relationships between perceived DTR
      usefulness and self-help processes, self-efficacy to cope with problems in
      recovery, and changes in behaviors conducive to dual recovery.  METHODS:
      Consumers attending DTR groups, located within a psychiatric day-treatment
      program, completed anonymous surveys 8 months (N=19) and 20 months (N=61) after
      DTR was implemented.  RESULTS: DTR participants rated DTR favorably and length of
      DTR attendance was significantly associated with increased self-efficacy for
      recovery and positive changes in recovery-oriented behaviors. Perceived DTR
      usefulness was significantly associated with greater engagement in three specific
      self-help processes and increased self-efficacy for recovery; notably, these
      associations were independent of consumers' overall satisfaction with the
      treatment program.  CONCLUSION: This study is the first to document consumers'
      perceived usefulness of DTR in relation to indicators of recovery. Overall, the
      study provides additional evidence for the benefits of implementing consumer-led
      dual focus groups in treatment programs.

PMID- 23136559
TI  - Fish oil and inflammatory status alter the n-3 to n-6 balance of the
      endocannabinoid and oxylipin metabolomes in mouse plasma and tissues.
AB  - It is well established that dietary intake of n-3 fatty acids is associated with
      anti-inflammatory effects, and this has been linked to modulation of the oxylipin
      and endocannabinoid metabolomes. However, the amount of data on specific tissue
      effects is limited, and it is not known how inflammation affects this relation.
      In the present study we systematically explored the combined effects of n-3 fatty
      acid diets and inflammation on the in vivo endocannabinoid and oxylipin
      metabolomes using a multicompartment, detailed targeted lipidomics approach. Male
      C57BL/6 mice received diets containing 0, 1, or 3 % w/w fish oil (FO) for 6
      weeks, after which 2 mg/kg LPS or saline was administered i.p. Levels of
      endocannabinoids/N-acylethanolamines (NAEs) and oxylipins, covering n-3 and n-6
      fatty acid derived compounds, were determined in plasma, liver, ileum and adipose
      tissue using LC-MS/MS. FO generally increased 'n-3' NAEs and oxylipins at the
      expense of compounds derived from other fatty acids, affecting all branches of
      the oxylipin metabolome. LPS generally increased levels of endocannabinoids/NAEs
      and oxylipins, with opposing effects across plasma and tissues. Multivariate data
      analysis revealed that separation between diet groups in the saline treated
      groups was primarily explained by decreases in other than n-3 derived compounds.
      In the LPS treated groups, the separation was primarily explained by increases in
      n-3 derived compounds. In conclusion, FO caused marked changes in the n-3 to n-6
      balance of the endocannabinoid and oxylipin metabolomes, with specific effects
      depending on inflammatory status. ELECTRONIC SUPPLEMENTARY MATERIAL: The online
      version of this article (doi:10.1007/s11306-012-0421-9) contains supplementary
      material, which is available to authorized users.

PMID- 23136560
TI  - NMR spectroscopy and chemometrics as a tool for anti-TNFalpha activity screening
      in crude extracts of grapes and other berries.
AB  - The identification of active ingredients in crude plant extracts offers great
      advantages. In this study, nuclear magnetic resonance and chemometrics were used
      for the screening of in vitro anti-TNFalpha activity in different berry types.
      Solid phase extraction was applied and the resulting water, methanol-water (1:1),
      and methanol fractions were tested for the activity. The methanol-water fraction
      contained most of the phenolics and showed significantly higher activity than the
      other two fractions. In the second phase of this study, grapes from
      'Trincadeira', 'Touriga Nacional', and 'Aragones', at four developmental stages
      were metabolically classified and tested for the TNFalpha inhibition. The initial
      stages of grape development, green and veraison, were found more active against
      TNFalpha production as compared to the later ripe and harvest stages. Among the
      cultivars, 'Touriga Nacional' was found to be the most potent inhibitor.
      Different multivariate data analyses algorithms based on projections to latent
      structures were applied to correlate the NMR and TNFalpha inhibition data. The
      variable importance in the projections plot showed that phenolics like quercetin,
      myricetin, (+)-catechin, (-)-epicatechin, caftarate, and coutarate, were
      positively correlated with high activity. This work demonstrates the great
      potential of NMR spectroscopy in combination with chemometrics for the screening
      of large set of crude extracts, to study the effects of different variables on
      the activity, and identifying active compounds in complex mixtures like plant
      extracts. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article
      (doi:10.1007/s11306-012-0406-8) contains supplementary material, which is
      available to authorized users.

PMID- 23136561
TI  - (1)H NMR-based metabolic profiling of urinary tract infection: combining multiple
      statistical models and clinical data.
AB  - Urinary tract infection (UTI) encompasses a variety of clinical syndromes ranging
      from mild to life-threatening conditions. As such, it represents an interesting
      model for the development of an analytically based scoring system of disease
      severity and/or host response. Here we test the feasibility of this concept using
      (1)H NMR based metabolomics as the analytical platform. Using an exhaustively
      clinically characterized cohort and taking advantage of the multi-level study
      design, which opens possibilities for case-control and longitudinal modeling, we
      were able to identify molecular discriminators that characterize UTI patients.
      Among those discriminators a number (e.g. acetate, trimethylamine and others)
      showed association with the degree of bacterial contamination of urine, whereas
      others, such as, for instance, scyllo-inositol and para-aminohippuric acid, are
      more likely to be the markers of morbidity. ELECTRONIC SUPPLEMENTARY MATERIAL:
      The online version of this article (doi:10.1007/s11306-012-0411-y) contains
      supplementary material, which is available to authorized users.

PMID- 23136562
TI  - Bilateral total knee arthroplasty with modified primary components in the
      management of neuropathic arthropathy related to chronic pancreatitis: a case
      with 5-year follow-up.
AB  - Although neuropathic arthropathy of the foot and ankle joints in diabetes is well
      known, the involvement of the knee joint is rare. Then, the management,
      particularly the use of arthroplasty, is a matter of debate. We report a 51-year
      old man with neuroarthropathic involvement of both knees related to the chronic
      pancreatitis treated by modified primary total knee arthroplasty components using
      augments and extension stems only on the tibial side. Our 5-year observations
      revealed that although the replacement surgery in neuroarthropathy is associated
      with high rate of complications, it is highly effective in avoiding progressive
      functional disability and durable. 

PMID- 23136563
TI  - Treatment of a chronic recurrent fistulized tibial osteomyelitis: administration
      of a novel antibiotic-loaded bone substitute combined with a pedicular muscle
      flap sealing.
AB  - Persistent osteomyelitis is a severe and challenging problem in bone surgery. We
      describe a surgical intervention in a young adult which combines a bone
      debridement process, a plastic muscle flap sealing and the administration of a
      novel bone substitution material with anti-infective properties. After 1 year,
      the patient showed no signs or symptoms of a reoccurrence of infection with full
      load capacity of the treated leg. 

PMID- 23136564
TI  - Therapeutic high-density barium enema in a case of presumed diverticular
      hemorrhage.
AB  - Many patients with lower gastrointestinal bleeding do not have an identifiable
      source of bleeding at colonoscopy. A significant percentage of these patients
      will have recurrent bleeding. In many patients, the presence of multiple
      diverticula leads to a diagnosis of presumed diverticular bleeding. Current
      treatment options include therapeutic endoscopy, angiography, or surgical
      resection, all of which depend on the identification of the diverticular source
      of bleeding. This report describes a case of recurrent bleeding in an elderly
      patient with diverticula but no identifiable source treated successfully with
      barium impaction therapy. This therapeutic modality does not depend on the
      identification of the bleeding diverticular lesion and was well tolerated by our
      86-year-old patient.

PMID- 23136565
TI  - Response to Modified TEGAFIRI in a Patient with Synchronous Multiple Liver
      Metastases of Colon Cancer.
AB  - We report the case of a patient with colon cancer accompanied by multiple
      unresectable liver metastases who showed complete response (CR) to modified
      TEGAFIRI (mTEGAFIRI) (tegafur-uracil/leucovorin+irinotecan) chemotherapy. The
      patient was a 58-year-old Japanese male with cancer of the descending colon
      accompanied by multiple unresectable liver metastases. Following resection of the
      sigmoid colon cancer, mTEGAFIRI chemotherapy was administered. Abdominal computed
      tomography performed upon completion of 12 courses of chemotherapy showed that
      the unresectable liver metastatic lesions had disappeared, indicating CR. The
      only adverse drug reactions (ADRs) experienced to date have been stomatitis
      (grade 1) and neutropenia (grade 1). Anticancer therapy has thus been continued,
      and CR has been maintained for 15 months. The present patient achieved CR in
      response to mTEGAFIRI chemotherapy, a regimen that has not previously been
      reported, while experiencing only mild ADRs and maintaining a good quality of
      life. mTEGAFIRI chemotherapy is convenient to administer and is thought to be a
      potentially useful treatment option for patients with unresectable, recurrent
      colon cancer.

PMID- 23136566
TI  - Pathologic review of cystic and cavitary lung diseases.
AB  - Pulmonary cystic and cavitary lesions caused by diverse etiologies are commonly
      encountered in chest imaging. The terms "cyst" and "cavity" are used to describe
      air-filled regions in the center of a nodule or consolidation of the lung. To
      date, only radiologic aspects of these lesions have been addressed. The
      morphologies of pulmonary cystic and cavitary lesions exhibit a broad spectrum,
      ranging from benign to malignant pulmonary diseases of acquired or congenital
      origin, including variable infectious diseases. In this review, we summarized the
      differential diagnosis of pathological entities to provide pathologists and
      radiologists with an overview of the diseases most commonly associated with
      pulmonary cystic and cavitary lesions in adults and children. The results showed
      slightly different patterns in the distribution of the diseases in the two
      groups. The most common causes of cavitary lesions include malignancy and
      infection in adults, and congenital malformation in children. Therefore,
      identification of pathologic entities correlating with the radiologic findings,
      clinical course, and location of the lesion is important in the evaluation of
      cystic and cavitary lung lesions in order to avoid unnecessary surgical
      procedures or delayed treatment.

PMID- 23136567
TI  - DPC4 expression in the small intestinal adenocarcinomas.
AB  - BACKGROUND: Small intestinal adenocarcinomas (SACs) are rare malignancies of the
      alimentary tract with uncertain carcinogenesis. METHODS: We investigated the
      expression of deleted in pancreatic cancer 4 (DPC4) in 188 cases of surgically
      resected SACs, using tissue microarray technology. RESULTS: Twenty-four of the
      188 tumors showed complete loss of Smad4/DPC4 expression in cytoplasm (score, 0;
      12.8%). Eighty-four and 31 cases were moderately and strongly positive,
      respectively (score, 2 and 3; 44.7% and 16.5%, respectively) and 49 cases were
      focally or weakly stained (score, 1; 29.1%). Immunohistochemistry analysis showed
      that the expression of Smad4/DPC4 was related to an increased risk of lymphatic
      invasion but not to other clinicopathological features of the tumors (tumor
      location, differentiation, growth pattern, T stage, direct invasion, vascular
      invasion, and nodal metastasis). There was no significant association between
      Smad4/DPC4 expression and patient survival. CONCLUSIONS: The present research is
      the first study to evaluate Smad4/DPC4 expression in a large sample of SACs with
      clinicopathologic correlation. Future studies should focus on the
      immunohistochemical and molecular characteristics of SACs to clarify their
      tumorigenesis.

PMID- 23136568
TI  - ERG immunohistochemistry and clinicopathologic characteristics in Korean prostate
      adenocarcinoma patients.
AB  - BACKGROUND: Transmembrane protease serine 2-ETS related gene (TMPRSS2-ERG) gene
      fusion, the most common genetic alternation in prostate cancer, is associated
      with protein expression of the oncogene ERG. Recently, an immunohistochemical
      staining method using an anti-ERG antibody was shown to have a strong correlation
      with altered ERG protein expression. METHODS: We analyzed a total of 303 radical
      prostatectomy specimens (obtained from Korean prostate cancer cases) using a
      constructed tissue microarray and ERG immunohistochemical staining. Thereafter,
      we evaluated the association between ERG expression and clinicopathological
      factors. RESULTS: The ERG-positive rate was 24.4% (74/303) and significantly
      higher ERG expression was observed in the subgroup with a lower Gleason score
      (p=0.004). Analysis of the histologic pattern of prostate adenocarcinomas
      revealed that tumors with discrete glandular units (Gleason pattern 3) displayed
      higher frequency of ERG expression (p=0.016). The ERG-positive rate was lower
      than that found (approximately 50%) in studies involving western populations.
      Other factors including age, tumor volume, initial protein-specific antigen
      level, a pathological stage and margin status were not significantly related with
      the ERG expression. CONCLUSIONS: ERG immunohistochemical staining is
      significantly higher in tumors with well-formed glands and is associated with a
      lower Gleason score.

PMID- 23136569
TI  - Expression of MUC1 and MUC4 in gallbladder adenocarcinoma.
AB  - BACKGROUND: Recent reports have indicated that overexpression of mucin (MUC) 1
      and/or MUC4 correlates with the occurrence and progression of extra-hepatobiliary
      malignancy. In this study, we investigated the expression of MUC1 and MUC4 and
      their prognostic significance in gallbladder adenocarcinoma. METHODS: We examined
      54 surgical gallbladder adenocarcinoma samples by immunohistochemistry for MUC1
      and MUC4 expression. Staining was evaluated as a sum score of extent and
      intensity, dividing the samples into low and high expression groups. RESULTS: The
      low expression group for both MUC1 and MUC4 was 10 samples (18.5%), and the high
      expression group was 44 samples (81.5%). High MUC1 expression was significantly
      correlated with more differentiated tumors (p=0.033), whereas high expression of
      MUC4 correlated with negative nodal status (p=0.012). Other pathological features
      were not correlated with MUC expression. Multivariate cox regression analysis
      showed that neither MUC1 nor MUC4 expression correlated with survival.
      CONCLUSIONS: Although there were some correlations found, a prognostic role for
      either MUC1 or MUC4 expression in gallbladder carcinoma was not identified in
      this study. Further investigation is required.

PMID- 23136570
TI  - A proposal for creating a guideline for cancer registration of the fibromatosis,
      PEComa group, malignant lymphoma In Situ and dendritic cell tumors (III).
AB  - BACKGROUND: Understanding the biologic behavior of a tumor is a prerequisite for
      tumor registration code assignment. The aim of this report was to propose
      appropriate behavior codes of the International Classification of Disease
      Oncology 3 (ICD-O3) to rare, yet pathologically interesting hematopoietic and
      soft tissue tumors. METHODS: The Study Group for Hematopathology, the Bone and
      Soft Tissue Pathology Study Group, and the Cancer Registration Committee prepared
      the questionnaire containing provisional behavior codes of selected diseases.
      RESULTS: In situ lesions of mantle cell and follicular lymphomas, dendritic cell
      tumors, and neoplasms with perivascular epithelioid cell differentiation
      (PEComa), not otherwise specified were classified as malignant (-/3). The
      fibromatosis group, with the exception of lipofibromatosis, was proposed as
      benign (-/0). Lipofibromatosis and several diseases that belong to the PEComa
      group were proposed as uncertain malignant potential (-/1). For the hematologic
      and soft tissue tumors, 274 and 288 members of the Korean Society of
      Pathologists, respectively, provided opinions through questionnaire, and most
      responders showed agreement with the provisional behavior code proposed.
      CONCLUSIONS: The determination of behavior codes for the rare diseases described
      in this study, especially those of the PEComa group or malignant lymphoma, could
      be viewed as impractical and premature, but this study provides the basis for
      future research on this topic.

PMID- 23136571
TI  - Update on the proposal for creating a guideline for cancer registration of the
      gastrointestinal tumors (I-2).
AB  - BACKGROUND: Cancer registries play a fundamental role in cancer control and
      multicenter collaborative research. Recently, the need for reassessment of cancer
      registry criteria has arisen due to the newly released 2010 World Health
      Organization (WHO) classification. Accordingly, development of new coding
      guidelines for cancer is necessary to improve the quality of cancer registries,
      as well as to prevent conflicts that may arise when seeking medical insurance
      compensation. METHODS: With funding from the Management Center for Health
      Promotion, 35 members of the Gastrointestinal Pathology Study Group and the
      Cancer Registration Committee of the Korean Society of Pathologists (KSP)
      participated in a second workshop for gastrointestinal tumor registration in
      Korea. RESULTS: The topics of gastric epithelial tumor, colonic intramucosal
      carcinoma, neuroendocrine tumor (NET), gastrointestinal stromal tumor (GIST) and
      appendiceal mucinous tumor were discussed for new coding guidelines. A survey was
      then conducted among 208 members of the KSP for a consensus of the guidelines
      proposed in the workshop. CONCLUSIONS: Although a few issues were set aside for
      further discussion, such as coding for non-gastric GIST and some types of NET,
      the members agreed upon most of the proposed guidelines. Therefore, we suggest
      using the newly revised International Classification of Diseases for Oncology,
      3rd edition (ICD-O-3) coding guidelines for registering gastrointestinal tumors
      in Korea.

PMID- 23136572
TI  - Expression of cortactin and focal adhesion kinase in colorectal adenocarcinoma:
      correlation with clinicopathologic parameters and their prognostic implication.
AB  - BACKGROUND: Cortactin and focal adhesion kinase (FAK) are two important
      components among actin cross-linking proteins that play a central role in cell
      migration. METHODS: The aims of this study were to evaluate the expression of
      cortactin and FAK in normal colorectal mucosa and colorectal adenocarcinoma (CRC)
      using tissue microarray of 2 mm cores to correlate their expression with other
      clinicopathological factors and, investigate their prognostic significance.
      RESULTS: Twenty (9%) and 24 cases (11%) of normal colorectal mucosa were
      immunoreactive for cortactin and FAK. In addition, 184 (84%) and 133 cases (61%)
      of CRCs were immunoreactive for cortactin and FAK, respectively. Cortactin
      expression was associated with histologic differentiation and FAK expression.
      Cortactin, but not FAK expression was also correlated with poor overall and
      relapse-free survival and served well as an independent prognostic factor for
      poor survival. CONCLUSIONS: Cortactin expression, in association with FAK
      expression, may plays an important role in tumor progression. Furthermore, it may
      also be a satisfactory biomarker to predict tumor progression and survival in CRC
      patients.

PMID- 23136573
TI  - Expression of CHOP in squamous tumor of the uterine cervix.
AB  - BACKGROUND: High-risk human papillomavirus (HR-HPV) infection and abnormal p53
      expression are closely involved in carcinogenesis of squamous cell carcinoma
      (SqCC) of uterine cervix. Recent studies have suggested that virus-induced
      endoplasmic reticulum (ER) stress modulates various cell survival and cell death
      signaling pathways. The C/EBP homologous protein (CHOP) is associated with ER
      stress-mediated apoptosis and is also involved in carcinogenesis of several human
      cancers. We hypothesized that CHOP is involved in the carcinogenesis of uterine
      cervical cancer in association with HR-HPV and/or p53. METHODS:
      Immunohistochemistry was used to analyze CHOP and p53 protein expression of
      tissue sections from 191 patients with invasive cancer or preinvasive lesions of
      the uterine cervix (61 cases of SqCC, 66 cases of cervical intraepithelial
      neoplasia [CIN] III, and 64 cases of CIN I). RESULTS: CHOP was expressed in 59.4%
      of CIN I, 48.5% of CIN III, and 70.5% of SqCC cases. It was also significantly
      more frequent in invasive SqCC than in preinvasive lesions (p=0.042). Moreover,
      CHOP expression significantly correlated with HR-HPV infection and p53 expression
      (p=0.009 and p=0.038, respectively). CONCLUSIONS: Our results suggest that CHOP
      is involved in the carcinogenesis of the uterine cervix SqCC via association with
      HR-HPV and p53.

PMID- 23136574
TI  - Clinicopathologic implication of ezrin expression in non-small cell lung cancer.
AB  - BACKGROUND: Ezrin, a member of the ezrin-radixin-moesin family, is implicated in
      tumor progression, metastatic dissemination, and adverse outcomes, in several
      cancer types. In this study, we explored the clinicopathological significance of
      ezrin expression in non-small cell lung carcinomas (NSCLCs). METHODS:
      Immunohistochemical analysis of tissue microarray with 112 surgically resected
      NSCLC specimens, was performed to examine the ezrin expression. We also
      correlated ezrin expression with other clinicopathological features and
      prognosis. RESULTS: The ezrin-positive group revealed significantly higher
      correlation with pleural invasion (p=0.016) and pathologic stage (p=0.050).
      Univariate survival analysis showed that ezrin-positive group had a significantly
      shorter cancer-specific survival than ezrin-negative group (p=0.016). Meanwhile,
      female (p=0.030), no pleural invasion (p=0.023), no lymphatic invasion (p=0.026),
      and early pathologic stage (p=0.008) significantly correlated with longer
      survival. Multivariate survival analysis showed that variables such as ezrin
      positivity (p=0.032), female (p=0.035), and early pathologic stage (p=0.001) were
      independent prognostic factors for NSCLC. CONCLUSIONS: Ezrin might be a molecular
      marker to predict poor prognosis of NSCLC.

PMID- 23136575
TI  - Ghost cell odontogenic carcinoma arising from calcifying cystic odontogenic
      tumor: a case report.
AB  - Ghost cell odontogenic carcinoma (GCOC) is an exceptionally rare and malignant
      odontogenic tumor with aggressive growth characteristics. We describe a case of
      GCOC which was considerably derived from a previously resected calcifying cystic
      odontogenic tumor (CCOT). Cellular atypia, mitotic activity, Ki-67 labeling index
      and matrix metalloprotease-9 positive expression rate were all increased in the
      currently resected specimen compared to the initial one. This is a rare case of
      malignant transformation of CCOT to GCOC with respect to its histopathological
      and immunohistochemical findings.

PMID- 23136576
TI  - Extraskeletal mesenchymal chondrosarcoma in the axillary region: reports of two
      cases.
AB  - Extraskeletal mesenchymal chondrosarcomas (EMCs) are relatively uncommon, and a
      location in the upper extremity, especially in the shoulder or axillary region,
      is rare. Furthermore, the radiographic findings of EMCs do not show any features
      that distinguish them from other neoplasms, and therefore, definitive diagnoses
      are made based on histological features. EMC is an aggressive tumor with a poor
      prognosis, and requires wide surgical excision. However, its treatment may
      involve peculiarities such as a difficulty in obtaining a proper surgical margin
      in the axillary region or shoulder. In this report, the authors present two rare
      cases of EMCs in the axillary region.

PMID- 23136577
TI  - Rosai-Dorfman Disease in the breast with increased IgG4 expressing plasma cells:
      a case report.
AB  - Rosai-Dorfman disease (RDD) can present in any anatomic site, but breast
      involvement is rarely reported. Recently, a relationship between RDD and IgG4
      related sclerosing disease has been suggested. Here we report another case of RDD
      with overlapping features of IgG4-related sclerosing disease occurring in a right
      breast of a 62-year-old female. On microscopic examination, the mass demonstrated
      a characteristic zonal pattern of proliferation of large polygonal histiocytes
      and lymphoplasma cells with stromal fibrosis. Emperipolesis was observed in
      histiocytes with abundant cytoplasm, which showed immunoreactivity for S-100
      protein and CD68; the diagnosis of RDD was made. Sheets of plasma cells in the
      fibrotic stroma demonstrated positive reactions for IgG and IgG4. The mean count
      of IgG4-positive plasma cells was 100.2/high power field, and the ratio of
      IgG4/IgG was 56.7%. Additional findings of stromal fibrosis and obliteration of
      preexisting breast lobules suggested overlapping features with IgG4-related
      sclerosing disease.

PMID- 23136578
TI  - Cellular pseudosarcomatous fibroepithelial stromal polyp of the vagina during
      pregnancy: a lesion that is overdiagnosed as a malignant tumor.
AB  - Fibroepithelial stromal polyp (FSP) is a benign lesion that can occur at various
      sites, including the lower female genital tract. In rare cases, however, it may
      exhibit hypercellularity, bizarre cytomorphological features, and atypical
      mitoses resulting in an overdiagnosis as a malignant tumor despite its benign
      clinical course. Recently, we experienced one case of a 30-year-old pregnant
      woman with cellular pseudosarcomatous FSP that was initially diagnosed as a
      malignant fibrous histiocytoma at a primary clinic. In addition to describing the
      rare features of this case, we wish to increase awareness about this benign
      lesion which will be essential for avoiding unnecessary radical surgery or
      chemoradiation treatment.

PMID- 23136579
TI  - Pigmented perivascular epithelioid cell tumor (PEComa) of the kidney: a case
      report and review of the literature.
AB  - Heavily pigmented perivascular epithelioid cell tumors (PEComa) are rare, only
      eight cases of which have been reported. Unlike typical epithelioid
      angiomyolipoma, most of these tumors have been encountered in female patients
      without tuberous sclerosis. The long-term prognosis thereof is undetermined.
      Cytological similarity and heavy melanin pigment make it difficult for pigmented
      PEComa to be differentiated from pigmented clear cell renal cell carcinoma or
      malignant melanoma. The immunoprofile of tumor cells, such as human melanoma
      black-45 expression, as well as the absence or presence of other melanocytic or
      epithelial markers, are helpful in determining a differential diagnosis. Here we
      report a case of heavily pigmented PEComa of the right kidney and review the
      literature describing this tumor. In this case, the immunoprofile and clinical
      features corresponded well to those described in the literature. Since the
      prognosis of such disease has not yet been established, close follow-up of this
      patient was recommended.

PMID- 23136580
TI  - Castleman's disease of the renal sinus presenting as a urothelial malignancy: a
      brief case report.
AB  - Castleman's disease is a rare benign lymphoproliferative disorder that frequently
      affects lymph nodes of the mediastinal thorax and the neck. It very rarely
      affects the renal sinus. We report a case of Castleman's disease arising in the
      renal sinus in a 64-year-old man. The patient visited the hospital with the chief
      complaint of hematuria. Abdominal computed tomography revealed a homogeneous mass
      in the sinus of the left kidney, radiologically interpreted as a malignant
      urothelial tumor. Subsequently, nephroureterectomy was performed, after which
      microscopic examination of the specimen revealed a diffuse lymphoproliferative
      lesion with reactive lymphoid follicles of various sizes and prominent plasma
      cell infiltration of interfollicular spaces, highlighted by immunohistochemical
      staining for CD138. The lesion was diagnosed as Castleman's disease of the plasma
      cell type. Although preoperative diagnosis of Castleman's disease is difficult
      and the incidence is exceedingly rare, it should be considered in the
      differential diagnosis of renal sinus tumors.

PMID- 23136581
TI  - Cytologic features of giant cell ependymoma: a case report and review of the
      literature.
AB  - Here, we present a case of anaplastic giant cell ependymoma (GCE) occurring in a
      15-year-old woman. Squash smear slides for intraoperative frozen section
      diagnosis revealed oval to round cell clusters with a papillary structure in a
      fibrillary background. This was occasionally accompanied by the presence of
      bizarre pleomorphic giant cells with hyperchromatic nuclei and prominent
      intranuclear inclusions. These intranuclear inclusions were a key clue to
      diagnosis of ependymoma. Histologic analysis revealed features of a high-grade
      tumor with perivascular pseudorosettes and bizarre pleomorphic giant cells, which
      established the diagnosis of GCE. We performed a review of literatures about the
      cytologic features of GCE, including our case, thus proposing that intraoperative
      frozen diagnosis of GCE would be established by squash smear preparations
      featuring the mitosis and necrosis, as well as the high cellularity, and the
      presence of giant cells showing hyperchromatic nuclei with eosinophilic cytoplasm
      and intranuclear inclusions/pseudoinclusions.

PMID- 23136582
TI  - Sex and speciation: the paradox that non-recombining DNA promotes recombination.
AB  - The benefits of sexual reproduction that outweigh its costs have long puzzled
      biologists. Increased genetic diversity generated by new allelic combinations, as
      enhanced by recombination during meiosis, is considered to be a primary benefit
      of sex. Sex-determining systems have evolved independently on numerous occasions.
      One of the most familiar is the use of sex chromosomes in vertebrates. Other
      eukaryotic groups also use sex chromosomes or smaller sex-determining regions
      within their chromosomes, such as the mating type loci in the fungi. In these
      organisms, sexual reproduction and its associated meiotic recombination is
      controlled by regions of the genome that are themselves blocked in recombination.
      Non-recombining DNA that is essential for recombination presents a paradox. One
      hypothesis is that sex-determination requires or leads to highly diverse alleles,
      establishing this block in recombination. A second hypothesis to account for the
      common occurrence of these types of sex-determining systems is that they combine
      mechanisms for recombination suppression and reproductive isolation, thereby
      promoting the evolution of new species. The fungal kingdom represents the ideal
      eukaryotic lineage to elucidate the functions of non-recombining regions in sex
      determination and speciation.

PMID- 23136583
TI  - Lipoprotein(a) and cardiovascular disease in diabetic patients.
AB  - Lipoprotein(a) (Lp[a]) is a LDL-like particle consisting of an ApoA moiety linked
      to one molecule of ApoB(100). Recent data from large-scale prospective studies
      and genetic association studies provide highly suggestive evidence for a
      potentially causal role of Lp(a) in affecting risk of cardiovascular disease
      (CVD) in general populations. Patients with Type 2 diabetes display clustered
      metabolic abnormalities and elevated risk of CVD. Lower plasma Lp(a) levels were
      observed in diabetic patients in several recent studies. Epidemiology studies of
      Lp(a) and CVD risk in diabetic patients generated inconsistent results. We
      recently found that Lp(a)-related genetic markers did not predict CVD in two
      diabetic cohorts. The current data suggest that Lp(a) may differentially affect
      cardiovascular risk in diabetic patients and in the general population. More
      prospective studies, Mendelian randomization analysis and functional studies are
      needed to clarify the causal relationship of Lp(a) and CVD in diabetic patients.

PMID- 23136584
TI  - The angiogenetic pathway in malignant pleural effusions: Pathogenetic and
      therapeutic implications.
AB  - Increased permeability of the pleural microvasculature is generally attributed to
      the substances that are released in inflammatory and malignant pleural effusions,
      although the exact pathogenetic mechanisms of malignant pleural effusions are
      unclear. Current therapies used to prevent the re-accumulation of pleural fluid
      and relieve symptoms are of variable efficacy and may cause serious adverse
      effects. Understanding the mechanisms of fluid accumulation would hopefully
      permit the development of more specific, effective and safer treatment
      modalities. Angiogenesis, pleural vascular increased permeability and
      inflammation are considered central to the pathogenesis of malignant pleural
      effusions. Vascular endothelial growth factor (VEGF) is a member of the
      VEGF/platelet-derived factor gene family and consists of at least six isoforms.
      Since it was shown that VEGF contributes to the formation of malignant pleural
      effusions, there have been some attempts to implicate, therapeutically, this
      finding using different molecules (ZD6474, PTK 787 and bevacizumab). However, the
      role of the biological axis of VEGF and angiopoietins needs further investigation
      in both the pathogenesis and the treatment of malignant pleural effusion. In both
      non-small-cell lung carcinoma and breast cancer, it has been shown that the
      ligand for CXCR4, CXCL12 or SDF-1alpha, exhibited peak levels of expression in
      organs that were the preferred destination for their respective metastases.
      Recent findings imply that new therapeutic strategies aimed at blocking the SDF-1
      CXCR4 axis may have significant applications for patients by modulating the
      trafficking of hemato/lymphopoietic cells and inhibiting the metastatic behavior
      of tumor cells as well. The purpose of this report is to review novel
      pathogenetic and therapeutic implications regarding the angiogenetic pathways in
      malignant pleural effusions.

PMID- 23136585
TI  - Circulating cytokeratin 18 fragments and activation of dormant tumor cells in
      bone marrow of cancer patients.
AB  - In cancer patients detection of systemic disease is of great importance to obtain
      prognostic information and to guide therapy. Bone marrow (BM) seems to be a
      common homing tissue for the early spread of tumor cells from various epithelial
      tumors; however, verification of the prognostic significance of BM-disseminated
      tumor cells (BM-DTCs), is restricted to breast cancer so far. These cells may be
      dormant for a long time, and signals triggering their activation leading to
      recurrence remain to be characterized. A recent study involving metastatic breast
      cancer patients reported that the shortest disease-free survival is correlated
      with cytokeratin (CK)-negative BM aspirates and that CK-positive BM-DTCs
      correspond to dormant tumor cells. Soluble CK fragments in serum including CK18
      and 19 (measured as TPS and CYFRA 21-1, respectively) and caspase-cleaved CK18
      are widely used to monitor tumor progression and response to therapy, actually
      indicating proliferation and/or necrotic/apoptotic cell death. In order to assess
      the source of the CK fragments, we used determinations of CK18 and caspase
      cleaved CK18 fragments in serum samples before and after radical tumor surgery in
      colon cancer patients. Elevated serum concentrations of CK18 were found to
      persist in patients with a high incidence of BM-DTCs, and high perioperative
      levels of caspase-cleaved CK18 fragments were detected in patients with early
      relapses, respectively. These results indicate that in some patients at increased
      risk of recurrence disseminated cell populations exist that are responsible for
      the release of the bulk of CK fragments after removal of the apparently
      nonmetastatic tumor. In good agreement with the results in metastatic breast
      cancer patients, release of CK18 or 19 fragments by BM-DTCs seem to indicate
      disseminated tumor cells mainly in a dormant state, whereas caspase-cleaved CK18
      may indicate skipping of this latent phase and early progression. Therefore,
      caspase cleavage of CKs in intact tumor cells seems to accompany or is involved
      in the differentiation leading from dormant to progressively active disseminated
      tumor cells. Release of respective CK fragments would result in an apparent
      clearing of CK-positive cells in BM, leaving malignant cells that have possibly
      undergone an epithelial-mesenchymal transition. Micrometastatic cancer cell lines
      derived from breast cancer patients were found to display loss of epithelial CK8,
      18 and 19 as well as ectopic expression of vimentin as in mesenchymal cells. In
      conclusion, degradation of CKs may represent a marker indicating reactivation of
      dormant tumor cells in BM.

PMID- 23136586
TI  - Psychological aspect of cancer: From stressor to cancer progression.
AB  - Substantial evidence indicates that psychological stress can influence the
      incidence and progression of cancers, and adequate psychotherapies are beneficial
      to cancer patients. Recently, the mechanisms responsible for the effects of
      psychological stress on cancer cells have been extensively investigated at the
      systemic, biochemical and molecular levels. Accumulating data indicate that the
      effects of psychological stress on cancer cells are mainly mediated by key stress
      related mediators and their corresponding receptors in multi-fold pathways:
      chronic stressors act on the paraventricular nucleus and the suprachiasmatic
      nuclei. The effects are then transmitted through the sympathetic nervous system
      and the hypothalamic-pituitary-adrenal axis, amplified by the unchecked release
      of stress-related mediators and altered behaviors. These mediators act as
      immunosuppressors or mitogens in the tumor microenvironment. The converging
      effects of psychological stress on cancer cells finally signal through receptors
      of the stress mediators and cytokines to activate the intracellular pro
      proliferative and pro-migratory signaling pathways, and reset the molecular clock
      in tumor cells. Understanding these action mechanisms of psychological stress in
      promoting the growth and invasion of cancer cells is crucial for devising
      effective interventions.

PMID- 23136587
TI  - The relationship between the molecular structure of natural acetogenins and their
      inhibitory activities which affect DNA polymerase, DNA topoisomerase and human
      cancer cell growth.
AB  - Acetogenins from the Annonaceous plant are a fatty acid-derived natural product.
      Chemically synthesized natural acetogenins, such as mucocin (compound 1),
      jimenezin (compound 2), muconin (compound 4), pyranicin (compound 5) and
      pyragonicin (compound 6) were investigated. Concomitantly, 19-epi jimenezin
      (compound 3), 10-epi pyragonicin (compound 7) and a gamma-lactone (compound 8),
      which is estimated to be a biosynthetic precursor of acetogenins, were
      synthesized and investigated. Compounds 5 and 6 strongly inhibited, and compound
      7 moderately inhibited the activities of mammalian DNA polymerases (pols), such
      as replicative pol alpha and repair/recombination-related pol beta and lambda,
      and also inhibited human DNA topoisomerase (topos) I and II activities. On the
      other hand, compounds 1-4 and 8 did not influence the activities of any pols and
      topos. Compound 5 was the strongest inhibitor of the pols and topos tested, and
      the IC(50) values were 5.0-9.6 MUM, respectively. These compounds also suppressed
      human cancer cell growth with almost the same tendency as the inhibition of pols
      and topos. Compound 5 was the strongest suppressor of the proliferation of the
      promyelocytic leukemia cell line, HL-60, in human cancer cell lines tested with
      an LD(50) value of 9.4 MUM, and arrested the cells at G1 phases, indicating that
      it blocks DNA replication by inhibiting the activity of pols rather than topos.
      This compound also induced cell apoptosis. The relationship between the three
      dimensional molecular structure of acetogenins and these inhibitory activities is
      discussed. The results suggested that compound 5 is a lead compound of
      potentially useful cancer chemotherapy agents.

PMID- 23136588
TI  - Clinical significance and prognostic value of S100A4 and matrix metalloproteinase
      14 in patients with organ-confined bladder cancer.
AB  - Various therapeutic modalities are available for treatment of bladder cancer, and
      their effectiveness and patient outcome often depend on cancer cell invasiveness.
      However, the mechanisms underlying the early steps of bladder cancer cell
      invasion remain unknown. This study aimed to clarify the relationships between
      S100A4 expression and bladder cancer invasion of surrounding muscles, prognosis
      and expression of matrix metalloproteinase (MMP)-14 in patients with organ
      confined bladder cancer. S100A4 and MMP-14 expression was analyzed in 85 cases of
      organ-confined (pTa, pT1 and pT2) bladder cancer using immunohistochemical
      technique. The expression levels were compared among the pTa, pT1 and pT2 tumors.
      In addition, the predictive values of S100A4 or MMP-14 expression for muscle
      invasion, metastasis and survival were investigated, as was the possible
      correlation between the expression of the two proteins. The proportion of S100A4
      positive cancer cells in pT2 tumors (53%) was significantly higher (p<0.001) than
      in pTa (38.7%) or pT1 (40.9%) tumors; there was no difference between pTa and
      pT1. The results were similar for MMP-14 expression, which was significantly
      correlated with S100A4 expression (r=0.360, p<0.001). S100A4 expression predicted
      metastasis-free survival (p=0.009), but not cause-specific survival. The results
      implicated S100A4 in the early steps of muscle invasion via MMP-14, but not for
      mucosal invasion. S100A4 is therefore a potential therapeutic target for bladder
      cancer, and its expression is a risk factor for muscle invasion in patients with
      superficial tumors. In addition, S100A4 expression may be a useful prognostic
      factor for metastasis in patients with organ-confined bladder cancer.

PMID- 23136589
TI  - Microarray-based determination of anti-inflammatory genes targeted by 6
      (methylsulfinyl)hexyl isothiocyanate in macrophages.
AB  - 6-(Methylsulfinyl)hexyl isothiocyanate (6-MSITC) is a bioactive ingredient of
      wasabi [Wasabia japonica (Miq.) Matsumura], which is a popular pungent spice of
      Japan. To evaluate the anti-inflammatory function and underlying genes targeted
      by 6-MSITC, gene expression profiling through DNA microarray was performed in
      mouse macrophages. Among 22,050 oligonucleotides, the expression levels of 406
      genes were increased by >=3-fold in lipopolysaccharide (LPS)-activated RAW264
      cells, 238 gene signals of which were attenuated by 6-MSITC (>=2-fold).
      Expression levels of 717 genes were decreased by >=3-fold in LPS-activated cells,
      of which 336 gene signals were restored by 6-MSITC (>=2-fold). Utilizing group
      analysis, 206 genes affected by 6-MSITC with a >=2-fold change were classified
      into 35 categories relating to biological processes (81), molecular functions
      (108) and signaling pathways (17). The genes were further categorized as
      'defense, inflammatory response, cytokine activities and receptor activities' and
      some were confirmed by real-time polymerase chain reaction. Ingenuity pathway
      analysis further revealed that wasabi 6-MSITC regulated the relevant networks of
      chemokines, interleukins and interferons to exert its anti-inflammatory function.

PMID- 23136590
TI  - Anticancer drug clustering based on proteomic profiles and a sensitivity database
      in a lung cancer cell line panel.
AB  - Previously, we performed a molecular pharmacological study that applied a
      combination of DNA microarray-based gene expression profiling and drug
      sensitivity tests in vitro with a view to designing an improved chemotherapeutic
      strategy for advanced lung cancer. Utilizing recent key technological advances in
      proteomics, particularly antibody array-based methodologies, the current study
      aimed to examine the benefit of protein expression profiling in an analogous
      molecular pharmacological context. We performed protein expression analysis in a
      panel of lung cancer cell lines via an antibody array approach. Using a modified
      NCI program, we related cell line-specific proteomic profiles to the previously
      determined cytotoxic activity of a selection of commonly used anticancer agents,
      namely docetaxel, paclitaxel, gemcitabine, vinorelbine, 5-fluorouracil (5-FU),
      SN38, cisplatin (CDDP) and carboplatin (CBDCA). In addition, we compared these
      results with those obtained from our prior DNA microarray-based transcriptomic
      study. In our expression-drug correlation analysis using antibody array,
      gemcitabine consistently belonged to an isolated cluster. Docetaxel, paclitaxel,
      5-FU, SN38, CBDCA and CDDP were gathered together into one large cluster. These
      results coincided with those generated by the prior transcriptomic study. Various
      genes were commonly listed that differentiated gemcitabine from the others. The
      identified factors associated with drug sensitivities were different between both
      analyses. Our proteomic profiling data provided confirmation of the previous
      transcript expression-drug sensitivity correlation analysis. These results
      suggest that chemotherapy regimens that include gemcitabine should be evaluated
      in second-line chemotherapy in cases where the first-line chemotherapy did not
      include this drug. Protein expression-drug sensitivity correlations in lung
      cancer cells in vitro may provide useful information in determining the most
      appropriate therapeutic options for lung cancer patients.

PMID- 23136591
TI  - Immunohistochemical expression of caspase-1 and -9, uncleaved caspase-3 and -6,
      cleaved caspase-3 and -6 as well as Bcl-2 in benign epithelium and cancer of the
      prostate.
AB  - Activation of caspases is an essential prerequisite for induction of apoptosis.
      In many tumors caspases are down-regulated, while anti-apoptotic Bcl-2 is up
      regulated. To elucidate their putative role in prostate cancer (PCa) we
      determined the expression of different caspases and Bcl-2 in benign prostate
      epithelium (BPE) and PCa. Paraffin-embedded prostate whole mounts were cut (4
      MUm) and investigated immunohistochemically using monoclonal antibodies against
      caspase-1 and -9, uncleaved caspase-3 and -6, cleaved caspase-3 and -6, and Bcl
      2. In BPE all caspases were localized to the cytoplasm of glandular cells. In PCa
      we found a statistically significant reduction in cleaved caspase-3 and -6
      compared to the levels in BPE. The Bcl-2 protein was detected in the basal
      compartment of epithelial gland cells, but no immunostaining was noted in PCa.
      The decreased immunoreactivity of activated caspases probably indicates an
      alteration in post-translational cleavage that may play an important role during
      PCa progression.

PMID- 23136592
TI  - Selection of chemotherapy for glioblastoma expressing O(6)-methylguanine-DNA
      methyltransferase.
AB  - The therapeutic benefit of nitrosoureas or temozolomide for glioblastoma is
      limited mainly by O(6)-methylguanine-DNA methyltransferase (MGMT) expression. The
      aim of this study was to evaluate the effectiveness of various anticancer drugs
      for MGMT-positive glioblastoma. Seventy-four glioblastoma patients were
      administered various anticancer drugs according to drug sensitivity testing. For
      the individualization, drug-induced apoptosis was quantified by flow cytometry in
      the primary culture of surgically resected tumor cells. The MGMT protein
      expression was analyzed by immunohistochemistry. The median survival of the
      patients receiving the individualized chemotherapy was 19.4 months (95% CI, 15.9
      22.1). The patients with negative MGMT immunostaining had significantly longer
      survival than those with positive MGMT immunostaining [median survival, 22.3
      months (95% CI, 17.6-27.0) vs. 15.1 months (95% CI, 13.4-16.8); p=0.0188]. For
      MGMT-positive tumors, the platinum agents and the taxanes were more frequently
      selected for administration than the other categories of anticancer agents. The
      patient survival period of MGMT-positive glioblastomas treated with the platinum
      agents or the taxanes [median survival, 20.1 months (95% CI, 18.0-22.7)] was
      significantly longer than that of MGMT-positive tumors treated with nitrosoureas
      (p=0.0026), and was equivalent to that of MGMT-negative glioblastomas (p=0.3047).
      These results suggest that the platinum agents and the taxanes offer the best
      probability to be effective against immunohistochemically MGMT-positive
      glioblastomas.

PMID- 23136593
TI  - Long-term maintenance of prognostic value of survivin and its relationship with
      p53 in T4 breast cancer patients.
AB  - A large proportion of human tumors show deregulated expression of a variety of
      proteins that play a crucial role in the execution of the apoptotic program.
      Survivin belongs to the family of inhibitor of apoptosis proteins which were
      originally identified in baculoviruses. Ectopic expression of survivin conveys
      resistance to apoptosis to a variety of stimuli, and survivin is one of the most
      abundantly overexpressed genes in human tumors such as breast cancer. In this
      study we examined the expression of survivin protein in a series of T4 breast
      cancers to identify any correlation with long-term patient outcomes. Moreover, we
      investigated the hypothesis of a possible association between p53 and survivin as
      a factor further complicating the outcome. Archival specimens from 53 T4 breast
      cancer patients were included in the study and treated for the
      immunohistochemical localization of survivin and p53 using the streptavidin
      biotin alkaline phosphatase method. The immunoreactivity was evaluated
      semiquantitatively according to the percentage of cells stained. Forty percent of
      tumors were positive for survivin. Statistical analysis revealed that survivin
      expression negatively influenced the 5- and 10-year disease-free and overall
      patient survival. In multivariate analysis, survivin expression was a significant
      independent prognostic indicator of worse outcome in overall survival [hazard
      ratio (HR)=2.61]. Our results showed that survivin is associated with a worse
      prognosis in patients with T4 breast cancer, and remarkably its prognostic
      relevance is maintained even long-term. Notably, p53 (HR=3.2) seems to negatively
      enhance the effect of survivin on survival.

PMID- 23136594
TI  - Evaluation of the chemosensitivity of primary cultured malignant melanoma cells
      using the collagen gel droplet-embedded culture drug sensitivity test.
AB  - Malignant melanoma usually shows resistance to a standard chemotherapy regimen. A
      useful in vitro method to evaluate individual chemosensitivity is required to
      select effective anti-cancer drugs. This study aimed to establish in vitro tumor
      response testing for malignant melanoma. We determined the chemosensitivity of
      primary cultured melanoma cells using the collagen gel droplet-embedded culture
      drug sensitivity test (CD-DST). Nineteen tests were carried out for 15 cases of
      malignant melanoma. Primary cultured melanoma cells in collagen gel droplets were
      exposed to anti-cancer drugs, including cisplatin, adriamycin, dacarbazine,
      nimustine and vincristine. After a 7-day incubation in a serum-free medium,
      living melanoma cells in a collagen droplet were detected by image analysis after
      staining with Neutral red reagent. In vitro drug exposure conditions were
      determined to reproduce the value of the plasma area under the time-drug
      concentration curve in vivo. The rate of evaluation of the primary culture of
      melanoma cells was 78.9% (15/19 tests). The chemosensitivity of cisplatin,
      adriamycin, dacarbazine, nimustine and vincristine was 15, 62, 0, 0 and 62%,
      respectively. Dacarbazine was not suitable for CD-DST due to its prodrug
      characteristics. The CD-DST method was able to evaluate the chemosensitivity of
      malignant melanoma to anti-cancer drugs in vitro. This method can also be applied
      to estimate the efficacy of newly developed anti-cancer drugs in vitro.

PMID- 23136595
TI  - Prognostic value of c-Met expression in oral squamous cell carcinoma.
AB  - Expression of c-Met, an oncogene encoding the receptor for the hepatocyte growth
      factor, was found to be associated with the progression of various types of human
      carcinomas including squamous cell carcinoma of the head and neck. This study was
      performed to analyze the prognostic role of c-Met in oral squamous cell carcinoma
      (OSCC) by detecting its expression in relation to clinicopathological features.
      Two hundred and eleven patients with OSCC were analyzed for c-Met expression by
      immunohistochemistry. Specimens with >=50% of cancer cells showing staining for c
      Met were considered c-Met-positive. A pairwise multiple-comparison procedure
      (Fisher's exact test) and survival analyses using the Kaplan-Meier method were
      used to analyze the data. One hundred and seventy-five patients (82.9%) showed
      positivity for c-Met, while 36 patients (17.1%) showed no immunopositivity. In
      contrast to published studies, there was no statistically significant correlation
      between c-Met expression and tumor size, lymph node status, distant metastasis or
      survival rates. However, a statistically significant negative correlation between
      c-Met expression and tumor stage was apparent (p=0.022). Hence, this study did
      not confirm the role of c-Met as a prognostic marker in patients with OSCC.

PMID- 23136596
TI  - Olfactomedin 4 (GW112, hGC-1) is an independent prognostic marker for survival in
      patients with colorectal cancer.
AB  - Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths
      worldwide. We previously performed Serial Analysis of Gene Expression (SAGE) on
      four primary gastric cancer samples and identified several gastric cancer
      specific genes. Of these genes, olfactomedin 4 (OLFM4, also known as GW112 or hGC
      1) is a candidate gene for cancer-specific expression. In the present study, we
      examined the expression and distribution of olfactomedin 4 in CRC by
      immunohistochemistry. Of the 176 CRC cases, 59 (34%) were positive for
      cytoplasmic staining of olfactomedin 4. Olfactomedin 4-positive CRC cases showed
      earlier T classification (P=0.0180), N classification (P=0.0149) and stage
      (P=0.0144) than olfactomedin 4-negative CRC cases. In the 176 CRC patients, those
      with olfactomedin 4-positive CRC had a better survival rate than patients with
      olfactomedin 4-negative CRC (P=0.0092). Multivariate analysis indicated that T
      classification, M classification and negative olfactomedin 4 expression were
      independent predictors of survival in patients with CRC. In addition to
      cytoplasmic staining of olfactomedin 4, stromal staining at the invasive front
      was observed. In total, 29 (16%) of the 176 CRC cases were positive for stromal
      olfactomedin 4; however, stromal olfactomedin 4 staining was not correlated with
      any clinicopathologic characteristic or with patient survival. These results
      indicate that olfactomedin 4 is a valuable marker for long-term survival in
      patients with CRC.

PMID- 23136597
TI  - Therapeutic effects of gamma-irradiation in a primary effusion lymphoma mouse
      model.
AB  - Primary effusion lymphoma (PEL) is a unique and recently identified non-Hodgkin's
      lymphoma in immunocompromised individuals. PEL is caused by the Kaposi sarcoma
      associated herpes virus/human herpes virus 8 (KSHV/HHV-8) and has a peculiar
      presentation involving liquid growth in the serous body cavity, chemotherapy
      resistance and poor prognosis. In search of a new therapeutic modality for PEL,
      we examined the effect of gamma-irradiation on PEL-derived cell lines (BCBL-1, BC
      1, and BC-3) in vitro and in vivo. An MTT assay and trypan blue exclusion assay
      revealed that irradiation significantly suppressed cell proliferation in the PEL
      cell lines in a dose-dependent manner, and induced apoptosis. The PEL cell lines
      were relatively radiosensitive compared with other hematological tumor cell lines
      (Raji, Jurkat, and K562 cells). Inoculation of the BC-3 cell line into the
      peritoneal cavity of Rag2/Jak3 double-deficient mice led to massive ascites
      formation, and subcutaneous injection of BCBL-1 led to solid lymphoma formation.
      Total body irradiation (4 Gy * 2) with bone marrow transplantation resulted in
      the complete recovery of both types of PEL-inoculated mice. These results suggest
      that total body irradiation with bone marrow transplantation can be successfully
      applied for the treatment of chemotherapy-resistant PEL.

PMID- 23136598
TI  - Telomerase activity in bladder cancer tissue.
AB  - Telomerase is a ribonucleoprotein enzyme that maintains telomeric DNA repeats at
      the end of chromosomes. Telomerase activity has been reported in many human
      cancers. The present study evaluated telomerase activity in bladder cancer tissue
      and investigated whether this activity is associated with tumor characteristics
      and prognosis in bladder cancer patients. Telomerase activity was investigated
      using the telomeric repeat amplification protocol (TRAP) in bladder tissue
      specimens from 81 patients, including 75 patients with bladder carcinoma and 6
      patients with dysplasia or an inflammatory bladder lesion. Forty-nine of the 75
      bladder cancer patients were found to be telomerase-positive, while 1 out of the
      6 control specimens without carcinoma was telomerase-positive. Telomerase
      activity was correlated with lower grade and lower stage bladder cancer, but was
      not significantly associated with cancer-specific survival in the total
      population of bladder cancer patients. However, telomerase-positive patients
      among the patients with invasive and grade 3 tumors had an improved prognosis.
      Telomerase activity was observed in early-stage bladder cancer, and may be an
      indicator of prognosis in bladder cancer patients with advanced-stage and high
      grade tumors.

PMID- 23136599
TI  - Increased serum cell-free DNA levels in relation to inflammation are predictive
      of distant metastasis of esophageal squamous cell carcinoma.
AB  - Distant metastasis hinders a favorable outcome for patients with esophageal
      squamous cell carcinoma (ESCC) by limiting the surgical cure. The levels of cell
      free DNA (cfDNA) in the blood have served as a predictor for metastasis and
      recurrence in distant organs in liver cancer. Thus, this study tested the
      clinical efficacy of serum cfDNA levels as a predictive marker for distant
      metastasis of ESCC. We investigated cfDNA levels in a cohort of 101 ESCC patients
      and 46 age- and gender-matched control patients with benign disease. We found
      that serum cfDNA levels were significantly higher in the ESCC patients than in
      the control patients (P=0.034). In the ESCC patients, serum cfDNA levels were
      positively associated with tumor size and cytokeratin 19 fragment (CYFRA 21-1)
      expression (r=0.416 and r=0.573, respectively). An increase in cfDNA levels was
      also associated with host inflammation status including C-reactive protein levels
      and neutrophil and monocyte numbers in the peripheral blood. Serum cfDNA levels
      tended to be higher in advanced tumors when compared to early stage tumors. We
      found that serum cfDNA levels were significantly higher in ESCC patients with
      distant metastasis than in those without (P=0.011). Logistic regression analysis
      showed that serum cfDNA levels represented only one independent risk factor for
      distant metastasis among the five factors tested including gender, age, cfDNA
      levels, CYFRA 21-1 and squamous cell carcinoma antigen levels (P=0.0414). These
      results suggest that increased serum cfDNA levels may serve as a useful predictor
      for distant metastasis of ESCC.

PMID- 23136600
TI  - Human MLH1 status can potentially predict cisplatin sensitivity but not
      microsatellite instability in head and neck squamous cell carcinoma cells.
AB  - Resistance to platinum-based chemotherapy frequently poses a serious problem in
      the treatment of head and neck squamous cell carcinoma. In this study, we
      isolated cisplatin-resistant cells from a head and neck squamous cell carcinoma
      cell line. The mismatch repair (MMR) system is known as one of the cisplatin
      resistant mechanisms. When the expression levels of hMLH1 and hMSH2, a mismatch
      repair gene and its gene product, were analyzed, the hMLH1 mRNA and protein
      expression levels were significantly decreased in the cisplatin-resistant cell
      lines compared with a cisplatin-sensitive cell line. In addition, the
      microsatellite instability (MSI) phenotype was examined for the absence of MMR.
      Our data support the hypothesis that hMLH1 mRNA and protein expression levels are
      predictors of cisplatin sensitivity, but MSI was not involved in cisplatin
      resistance. The status of hMLH1 predicts the sensitivity of head and neck
      squamous cell carcinoma to platinum-based chemotherapy.

PMID- 23136601
TI  - Alterations in the Th1/Th2 balance in breast cancer patients using reflexology
      and scalp massage.
AB  - The diagnosis and treatment of breast cancer can adversely affect quality of
      life. Here the aim was to determine the effects of reflexology on host defences
      and endocrine function in women with early breast cancer. Six weeks after surgery
      for early breast cancer, 183 women were randomly assigned to self-initiated
      support (SIS), SIS plus foot reflexology, or SIS plus scalp massage. Peripheral
      blood mononuclear cells and serum were isolated at T1 (6 weeks post surgery;
      baseline), T2 and T3 (4 and 10 weeks post completion of intervention,
      respectively). Lymphocyte phenotyping found that CD25(+) cells were significantly
      higher in the massage group compared with the SIS group at T3. The percentage of
      T cells, and more specifically the T helper subset expressing IL4, decreased
      significantly in the massage group compared with the SIS group at T3. This change
      was accompanied by an increase in the percentage of CD8(+) T cytotoxic cells
      expressing IFNgamma in the massage group. Natural killer and lymphokine activated
      killer cell cytotoxicity measurements, serum levels of cortisol, prolactin and
      growth hormone, and flow cytometric assessment of their corresponding receptors
      all revealed no significant differences between the three groups of patients.
      This study provides evidence that the immunological balance of patients can be
      altered in a potentially beneficial manner by massage. The original trial was
      registered with the International Standard Randomised Controlled Trial Registry
      (ISRCTN87652313).

PMID- 23136602
TI  - HMGB1: A new marker for estimation of the postmortem interval.
AB  - Estimation of the postmortem interval (PMI) is one of the most important tasks in
      forensic medicine. Numerous methods have been proposed for the determination of
      the time since death by chemical means. High mobility group box-1 (HMGB1), a
      nonhistone DNA-binding protein is released by eukaryotic cells upon necrosis.
      Postmortem serum levels of HMGB1 of 90 male Wistar rats stored at 4, 14 and 24
      degrees C since death were measured by enzyme-linked immunosorbent assay. The
      serum HMGB1 level showed a time-dependent increase up to seven days at 4 degrees
      C. At 14 degrees C, the HMGB1 level peaked at day 3, decreased at day 4, and then
      plateaued. At 24 degrees C, the HMGB1 level peaked at day 2, decreased at day 3,
      and then plateaued. Our findings suggest that HMGB1 is related to the PMI in
      rats.

PMID- 23136603
TI  - Combined influence of adjuvant therapy and interval after surgery on peripheral
      CD4(+) T lymphocytes in patients with esophageal squamous cell carcinoma.
AB  - The aim of this study was to investigate possible differences in cellular
      immunity between chemo- and/or radiotherapy groups during a long interval after
      surgery in esophageal squamous cell carcinoma (ESCC) patients. Cellular immunity
      was assessed as peripheral lymphocyte subsets in response to chemotherapy (CT),
      radiotherapy (RT) and CT+RT by flow cytometric analysis. There were 139 blood
      samples obtained at different time points relative to surgery from 73 patients
      with ESCC. The changes in the absolute and relative proportions of lymphocyte
      phenotypes were significant among the adjuvant therapy groups. There were
      significant differences in the absolute counts of CD4(+) and CD8(+) T cells among
      the interval groups, and a lower CD4/CD8 ratio was found in patients following a
      prolonged interval. RT alone had a profound effect on the absolute counts of
      CD3(+), CD4(+) and CD8(+) T cells compared with the other groups. CD4(+) T cells
      exhibited a decreasing trend during a long interval, leading to a prolonged T
      cell imbalance after surgery. Univariate analysis revealed that the interaction
      of the type of adjuvant therapy and the interval after surgery was correlated
      only with the percentage of CD4(+) T cells. The percentage of CD4(+) T cells can
      be used as an indicator of the cellular immunity after surgery in ESCC patients.
      However, natural killer cells consistently remained suppressed in ESCC patients
      following adjuvant therapy after surgery. These findings confirm an interaction
      between adjuvant therapy and the interval after surgery on peripheral CD4(+) T
      cells, and implies that adjuvant therapy may have selective influence on the
      cellular immunity of ESCC patients after surgery.

PMID- 23136604
TI  - Thiopurine S-methyltransferase alleles, TPMT(*)2, (*)3B and (*)3C, and genotype
      frequencies in an Indian population.
AB  - Thiopurine S-methyltransferase (TPMT) catalyzes the S-methylation of aromatic and
      heterocyclic sulfhydryl compounds including thiopurine drugs such as 6
      mercaptopurine, 6-thioguanine and azathioprine. TPMT activity exhibits genetic
      variation and shows tri-modal distribution with 89-94% of individuals possessing
      high activity, 6-11% intermediate activity and approximately 0.3% low activity.
      Patients with intermediate or deficient TPMT activity exposed to thiopurine drugs
      show severe hematopoietic toxicity. Three single nucleotide polymorphisms (SNPs)
      in TPMT (NM_000367.2:c.238G>C, NM_000367.2:c.460G>A and NM_000367.2:c.719A>G)
      define the most prevalent mutant alleles associated with loss of catalytic
      activity reported in several populations. The present study investigated, for the
      first time, the frequency distribution of these three SNPs of TPMT, their alleles
      and genotypes in a Southern Indian population. Peripheral blood was obtained from
      326 individuals of a Southern Indian population, and genomic DNA was isolated
      from total peripheral white blood cells. The genotypes at the polymorphic loci
      were determined by allele-specific polymerase chain reaction, restriction
      fragment length polymorphism and confirmatory DNA sequencing. The estimated
      genotype frequency for homozygous TPMT(*)1/(*)1 was 97.24%, for heterozygous
      TPMT(*)1/(*)2 and TPMT(*)1/(*)3B, 0.61% each, and for heterozygous
      TPMT(*)1/(*)3C, 1.53%. The frequency of heterozygous mutants in the studied
      Indian population was 2.76%. This study demonstrated significant variations in
      TPMT gene polymorphisms in an Indian population in relation to other human
      populations and may help to predict both clinical efficacy and drug toxicity of
      thiopurine drugs.

PMID- 23136605
TI  - Selenium-Bifidobacterium longum as a delivery system of endostatin for inhibition
      of pathogenic bacteria and selective regression of solid tumor.
AB  - Bifidobacterium longum (B. longum) as a delivery system for endostatin was shown
      to have definite antitumor effects. Moreover, it was found that the enrichment of
      selenium was able to enhance the immunity of mice. In order to further evaluate
      the safety and efficacy of B. longum carrying pBV22210-endostatin (B. longum-En)
      enriched with selenium (Se-B. longum-En), we determined the biochemical
      characteristics of Se-B. longum-En. We then investigated its effect on macrophage
      activity, as well as its inhibitory effect on the multiplication of pathogenic
      bacteria in vitro and the antitumor effects on murine hepatic (H22) tumor-bearing
      mice. The results showed that Se-B. longum-En exhibited similar biochemical
      characteristics to that of wild-type B. longum, i.e., Se-B. longum-En strongly
      enhanced macrophage phagocytosis in rats and inhibited the growth of pathogenic
      bacteria. In addition, Se-B. longum-En showed a definite inhibitory effect of
      tumor growth when H22 tumor-bearing mice were fed through oral or tail vein
      delivery. These results suggested that Se-B. longum is able to retain the
      advantages of wild-type B. longum and be used as a novel gene delivery system for
      liver cancer gene therapy.

PMID- 23136606
TI  - Association of genetic variants with chronic kidney disease in Japanese
      individuals with or without hypertension or diabetes mellitus.
AB  - Hypertension and diabetes mellitus are important risk factors for chronic kidney
      disease (CKD). The purpose of the present study was to identify genetic variants
      that confer susceptibility to CKD in individuals with or without hypertension or
      diabetes mellitus, thereby contributing to the personalized prevention of CKD in
      such individuals separately. The study population comprised 5835 unrelated
      Japanese individuals, including 1763 subjects with CKD and 4072 controls. The 150
      polymorphisms were selected by genome-wide association studies of ischemic stroke
      and myocardial infarction with the use of the GeneChip Human Mapping 500K Array
      Set (Affymetrix). The genotypes for these polymorphisms were determined by a
      method that combines polymerase chain reaction and sequence-specific
      oligonucleotide probes with suspension array technology. The chi(2) test,
      multivariable logistic regression analysis with adjustment for covariates, as
      well as a stepwise forward selection procedure revealed that two different
      polymorphisms were significantly (P<0.005) associated with the prevalence of CKD
      in individuals with or without hypertension or diabetes mellitus: the A->G
      (Lys625Arg) polymorphism of CDH4 (rs6142884) in individuals without diabetes
      mellitus, and the C->T polymorphism of PTPRN2 (rs1638021) in individuals with
      hypertension and diabetes mellitus. No polymorphism was significantly associated
      with CKD in individuals with or without hypertension, in those with diabetes
      mellitus, or in those without hypertension or diabetes mellitus. Stratification
      of subjects based on hypertension or diabetes mellitus may thus be fundamental to
      achieving the personalized prevention of CKD with the use of genetic information.

PMID- 23136607
TI  - Physiotherapeutic stimulation: Early prevention of lymphedema following axillary
      lymph node dissection for breast cancer treatment.
AB  - The aim of this study was to confirm the effectiveness of early physiotherapeutic
      stimulation for lymphatic flow progression in patients with breast cancer
      undergoing axillary dissection. This was a randomized experimental study on 22
      patients who underwent lymphoscintigraphy in their arms on two different
      occasions, firstly without stimulation and secondly after randomization into two
      groups: without physiotherapeutic stimulation (WOPS; n=10) and with
      physiotherapeutic stimulation (WPS; n=12). The lymphoscintigraphy scan was
      performed with (99m)Tc-phytate administered into the second interdigital space of
      the hand, ipsilaterally to the dissected axilla, in three phases: dynamic,
      static, and delayed whole body imaging. Physiotherapeutic stimulation was carried
      out using Foldi's technique. In both groups, images from the two examinations of
      each patient were compared. Flow progression was considered positive when, on the
      second examination, the radiopharmaceutical reached areas more distant from the
      injection site. Statistical analysis was used to evaluate frequencies,
      percentages and central trend measurements, and non-parametric tests were
      conducted. Descriptive analysis showed that the WPS and WOPS groups were similar
      in terms of mean age, weight, height, body mass index and number of lymph nodes
      removed. There were statistically significant associations between
      physiotherapeutic stimulation and radiopharmaceutical progression at all three
      phases of the study (p<0.0001). Early physiotherapeutic stimulation in breast
      cancer patients undergoing radical axillary dissection is effective, and can
      therefore be indicated as a preventive measure against lymphedema.

PMID- 23136608
TI  - Expression of the ERM family members (ezrin, radixin and moesin) in breast
      cancer.
AB  - The ERM family is composed of the proteins ezrin, moesin and radixin, which are
      cell structure-related proteins. Despite the detection of viable roles of ERM
      family proteins, the impact of these molecules in cancer pathogenesis has yet to
      be investigated. Evidence emerging from clinical and translational studies showed
      that the ERM family is linked to disease progression in clinical cancers. We
      aimed to establish the pattern of expression of the ERM proteins and deduce a
      possible relationship between these molecules and clinical outcome in a cohort of
      human breast cancers. The expression of the three ERM molecules at the mRNA and
      protein levels in a cohort of 122 human breast cancers and 32 normal breast
      tissues were analysed and correlated with pathological and clinical information
      as well as patient outcome. The three molecules were positively stained in
      mammary tissues while the staining pattern was lost in the malignant cells. Low
      levels of moesin and radixin transcripts were seen in tumours from patients with
      metastasis, local recurrence and in patients who succumbed to the disease
      (moesin: p=0.039, p=0.037 and p=0.066, respectively, and radixin: p=0.039,
      p=0.039 and p=0.04, respectively). Ezrin levels were significantly lower in
      tumour recurrence and in patients who succumbed to the disease (p=0.0001 and
      p=0.59, respectively). Using the Kaplan-Meier survival analysis, a general trend
      of higher levels of ERM was observed, with marginal long overall and disease-free
      survival. In conclusion, an inverse relationship between ERM expression and
      tumour behaviour of breast cancer patients was noted. However, further work needs
      to be conducted in other types of cancer in clinical situations to obtain
      consistent results.

PMID- 23136609
TI  - Genome-wide comparison of FGFRL1 with structurally related surface receptors.
AB  - FGFRL1 (FGFR5) is a member of the fibroblast growth factor receptor family, which
      lacks the intracellular tyrosine kinase domain required for signal transduction
      by trans-phosphorylation. Since it still contains a cytoplasmic domain of 100
      amino acid residues with a peculiar histidine-rich element, it might be involved
      in an alternative pathway of downstream signaling. To get a clue about a possible
      mechanism, we compared the overall structure of FGFRL1 with all proteins from the
      UniProt databank. We found that the human genome encodes 42 structurally related
      proteins with a signal peptide, three Ig-like domains and a transmembrane domain.
      These proteins can be grouped in seven families, fibroblast growth factor
      receptors (FGFRs), Fc receptor-like proteins, IL-1 receptor-like proteins, killer
      cell Ig-like receptors (KIRs), nectin-like proteins, sialic acid binding lectins
      (SIGLECs) and signal regulatory proteins (SIRPs). The 7 families utilize four
      different strategies for signaling, namely a protein tyrosine kinase domain, a
      TIR (Toll/IL-1 receptor) domain, ITIM/ITAM motifs as well as carboxy-terminal
      peptides that interact with the PDZ domain of an adaptor protein. It remains to
      be determined whether FGFRL1 might also utilize one of these strategies for
      signaling.

PMID- 23136610
TI  - Adverse effect of mild temperature hyperthermia combined with
      hexamethylenetetramine compared to its effect combined with tirapazamine in the
      treatment of solid tumors.
AB  - This study aimed to assess the effect on solid tumors of mild temperature
      hyperthermia (MTH) combined with hexamethylenetetramine (HMTA) or tirapazamine
      (TPZ). Squamous cell carcinoma (SCC VII) tumor-bearing mice were continuously
      administered 5-bromo-2'-deoxyuridine (BrdU) to label intratumor proliferating (P)
      cells. Mice received HMTA or TPZ through intraperitoneal single or subcutaneous
      continuous administration, with or without MTH (40 degrees C, 60 min), followed
      or not by gamma-ray irradiation or cisplatin treatment. After HMTA or TPZ
      administration without gamma-ray irradiation or cisplatin treatment, immediately
      after gamma-ray irradiation, or 1 h after cisplatin treatment, the response of
      quiescent (Q) cells was assessed in terms of micronucleus frequency using
      immunofluorescence staining for BrdU. The response of the total (P + Q) tumor
      cells was determined based on a comparison with non-BrdU-treated tumors. Without
      MTH, HMTA and TPZ had a nearly equal radiosensitizing and cisplatin sensitivity
      enhancing effect on both total and Q cells. With MTH, radio- and cisplatin
      sensitizing effects by HMTA were reduced, particularly in the Q cells. In
      contrast, the enhancing effects of TPZ were increased, particularly in the Q
      cells. Continuous administration of HMTA and TPZ resulted in higher radio- and
      cisplatin-sensitizing effects than intraperitoneal single administration. In
      terms of tumor cytotoxicity as a whole, including Q cells, the administration of
      gamma-ray irradiation or cisplatin treatment combined with continuous HMTA
      administration is promising, taking into account the clinical use of HMTA.
      However, MTH should not be combined with HMTA administration.

PMID- 23136611
TI  - High-sensitivity C-reactive protein and liver enzymes in individuals with
      Metabolic Syndrome in Talca, Chile.
AB  - Metabolic syndrome (MS) is a core set of disorders, including abdominal obesity,
      dyslipidemia, hypertension and hypertriglyceridemia that together predict the
      development of diabetes type 2 and cardiovascular disease. This study
      investigated the relationship between liver enzyme levels and high-sensitivity C
      reactive protein (hs-CRP) in subjects with and without MS. Alanine
      aminotransferase (ALAT), aspartate-aminotransferase (ASAT), gamma-glutamyl
      transferase (GGT) and hs-CRP were measured in 510 subjects, aged 40 to 65 years
      old. Patients were selected from 1007 subjects from the Research Program for
      Cardiovascular Disease Risk Factors in Talca, Chile. Results showed that women
      with MS presented higher liver enzyme levels than those who did not have MS. This
      was not observed in male patients for the enzymes ALAT and ASAT. However, GGT and
      hs-PCR levels were higher in male and female patients with MS than in those
      without MS. In conclusion, it is important to search for the presence of MS when
      diagnosing fatty liver. Moreover, the presence of liver disease in patients with
      MS should be further investigated.

PMID- 23136612
TI  - In vitro anti-proliferative activity of alcoholic stem extract of Coscinium
      fenestratum in human colorectal cancer cells.
AB  - Coscinium fenestratum (Gaertn.) Colebr. is traditionally used for the treatment
      of cancer, arthritis and diabetes mellitus. The purpose of this study was to
      determine the molecular mechanisms by which this plant shows beneficial effects.
      An 80% ethanolic extract of C. fenestratum (80ET) was separated by its polarity
      into dichloromethane (DCM) and aqueous fractions (WF), and the anti-proliferative
      effects of 80ET, DCM and WF were investigated. Berberine, one of the major
      components of C. fenestratum, was used as a control. The 80ET, DCM, WF and
      berberine showed anti-proliferative activity as assessed by cell growth assay.
      Subsequently, the pro-apoptotic proteins NAG-1 and ATF3 were increased and the
      cell cycle protein cyclin D1 was decreased by the extract and its fractions.
      Interestingly, only the DCM fraction exhibited the induction of peroxisome
      proliferator-activated receptor gamma (PPARgamma) binding activity, which
      represents a pro-apoptotic activity in colorectal cancer cells. The overall
      results of this study indicate that the extract from this plant has anti
      proliferative activity through the activation of pro-apoptotic proteins and
      PPARgamma, and may have potential as a preventive regimen in the treatment of
      cancer.

PMID- 23136613
TI  - Gene expression patterns in the histopathological classification of epithelial
      ovarian cancer.
AB  - The purpose of this study was to screen cancer-related genes and to identify
      histopathological gene expression patterns as potential biomarkers in human
      epithelial ovarian cancer (EOC). Fifty genes were screened by reverse
      transcription polymerase chain reaction assay with cDNA from 83 EOC tissues and
      48 normal ovarian specimens of ovarian cancer patients and evaluated by gel
      electrophoresis analysis. Twenty expressed genes were assessed by real-time
      relative-quantity (RQ)-PCR in 30 EOC specimens for gene signature study. Four
      genes, TAL2, EGF, ILF3 and UBE2I, were investigated for gene expression patterns
      in histopathological classification of EOC. RQ-value (Ct, DeltaCt, DeltaDeltaCt,
      RQ and gene expression plots) was generated by ABI 7500 Fast System SDS Software
      (version 1.4). SPSS 15.0 software was used for statistical analysis. Using real
      time RQ-PCR, we found that TAL2, EGF, ILF3 and UBE2I demonstrated distinct
      expression patterns in histological types of epithelial ovarian cancer. The
      expression of ILF3 and UBE2I in tumors was significantly higher than in normal
      tissue, with extremely high expression in serous carcinomas compared to mucinous,
      endometrium and clear cell carcinomas. In addition, ILF3 and UBE2I were
      overexpressed in advanced stage and advanced grade ovarian cancer, compared to
      early stage or well-differentiated ovarian cancer. This is the first report of
      TAL2 and ILF3 expression in the normal human ovary and epithelial ovarian cancer.
      Our results indicate that overexpression of ILF3 and UBE2I in advanced stage and
      advanced grade suggest that these two genes may play an important role in
      tumorigenesis/tumor progression and pathological differentiation of the disease.
      Notably, ILF3 plays a role in DNA binding activity and transcriptional and post
      transcriptional regulation; UBE2I is required in ubiquitination and sumoylation
      and is involved in DNA repair and apoptosis of cells. Further investigations to
      reveal the molecular mechanisms related to the activation of ILF3 and UBE2I in
      the development of EOC are warranted.

PMID- 23136614
TI  - Hybrid capture II for high-risk human papillomavirus DNA testing to detect
      cervical precancerous lesions: A qualitative and quantitative study.
AB  - Hybrid capture II (HC-II) is the only technique that can be used in clinical
      human papillomavirus (HPV) DNA detection. However, there is controversy in
      regards to how to analyze and assess the viral load of high-risk (HR)-HPV by use
      of HC-II and the relation between viral load and cervical lesions. In this study,
      we analyzed the results of a sequential screening of outpatients at the
      Department of Obstetrics and Gynecology of the China-Japan Friendship Hospital,
      and we aimed to explore the relationship between HR-HPV viral load and the
      severity of cervical lesions, and to clarify the clinical significance of the
      titer of HR-HPV DNA determined by HC-II. Using HC-II, 2,761 women were screened
      for HR-HPV DNA combined with cytological testing using liquid-based cytology. All
      women with HR-HPV-positive results or abnormalities in cytology underwent a
      cervical biopsy through colposcopy. Cervical biopsies were taken in 1,051 women.
      The HR-HPV infection rate was 78.35% (76/97) in HPV-associated lesions, 87.33%
      (193/221) in cervical intraepithelial neoplasia (CIN) I, 94.74% (144/152) in CIN
      II, 100% (178/178) in CIN III and 100% (20/20) in invasive cervical cancer (ICC),
      respectively (P<0.05). Based on the criteria of histopathology, the sensitivity
      of HR-HPV DNA testing by HC-II for detecting high-grade cervical lesions was
      97.71%, the specificity was 79.64%, the positive-predictive value was 41.06% and
      the negative-predictive value was 99.59%. The viral loads of HR-HPV DNA were
      512.15+/-764.19 in HPV-associated lesions, 753.95+/-978.27 in CIN I, 871.08+/
      1003.52 in CIN II, 603.40+/-740.25 in CIN III and 466.44+/-673.05 in ICC,
      respectively. In conclusion, the positive rate of HR-HPV increased significantly
      in accordance with the severity of cervical lesions. The viral loads of cervical
      inflammatory lesions were markedly lower than CINs and ICC. The viral loads of HR
      HPV DNA tested by HC-II had no correlation with the grade of cervical lesions.

PMID- 23136615
TI  - Outcome after emergency surgery in patients with a free perforation caused by
      gastric cancer.
AB  - Perforation of gastric cancer is rare and it accounts for less than 1% of the
      incidences of an acute abdomen. In this study, we reviewed cases of benign or
      malignant gastric perforation in terms of the accuracy of diagnosis and
      investigated the clinical outcome after emergency surgery in patients with a free
      perforation caused by gastric cancer. On the basis of pathological examination,
      gastric cancer was diagnosed in 8 patients and benign ulcer perforation in 32
      patients. The sensitivity, specificity and accuracy of intraoperative diagnosis
      by pathological examination were 50, 93.8 and 85%, respectively. Except for age,
      there were no differences in the other demographic characteristics between
      patients with gastric cancer and benign ulcer perforation. The median survival
      time of patients with perforated gastric cancer was 195 days after surgery.
      Patients with gastric cancer perforation had a poorer overall survival rate than
      those who had T3 tumors without perforation. In addition, in patients with
      perforation, recurrence of peritoneum occurred more frequently. In conclusion, to
      improve the survival rate of patients with perforated gastric cancer and to
      improve the accuracy of intraoperative diagnosis, endoscopic examination and/or
      pathological examination of the frozen section should be performed, if possible.
      A balanced surgical strategy using laparoscopic local repair as the first-step of
      surgery, followed by radical open gastrectomy with lymphadenectomy may be
      considered.

PMID- 23136616
TI  - Accuracy of (99m)Tc-sestamibi scintimammography for breast cancer diagnosis.
AB  - Scintimammography using (99m)Tc-sestamibi is a noninvasive and painless
      diagnostic imaging method that is used to detect breast cancer when mammography
      is inconclusive. Because of the advantages of labeling with (99m)Tc-sestamibi and
      its high efficiency in detecting carcinomas, it is the most widespread agent for
      this purpose. Its accumulation in the tumor has multifactorial causes and does
      not depend on the presence of architectural distortion or local or diffuse
      density variation in the breast. The objective of this study was to evaluate the
      accuracy of scintimammography for detecting breast cancer. One hundred and fifty
      seven patients presenting 158 palpable and non-palpable breast nodules were
      evaluated. Three patients were male and 154 were female, aged between 14 and 81
      years. All patients underwent scintimammography, and the nodule was subjected to
      cytological or histological study, i.e., the gold standard for diagnosing cancer.
      One hundred and eleven malignant and 47 benign nodules were detected, with
      predominance of ductal carcinomas (n=94) and fibroadenoma/fibrocystic condition
      (n=11/n=11), respectively. The mean size was 3.11 cm (7-10 cm) among the
      malignant nodules and 2.07 cm among the benign nodules (0.5-10 cm). The
      sensitivity, specificity, positive predictive value, negative predictive value
      and accuracy were 89, 89, 95, 78 and 89%, respectively. Analysis on the
      histological types showed that the technique was more effective on tumors that
      were more aggressive, such as ductal carcinoma. In this study, (99m)Tc-sestamibi
      scintimammography was shown to be an important tool for diagnosing breast cancer
      when mammography was inconclusive.

PMID- 23136617
TI  - Genomic analysis of invasion-metastasis-related factors in pancreatic cancer
      cells.
AB  - Pancreatic cancer is known to be an extremely lethal neoplasm, one of the reasons
      being that pancreatic cancer itself has an extremely high potential of invasion
      metastasis. In our previous study, two pancreatic cancer cell lines with a
      different potential for invasion-metastasis, PC-1 with a low potential and PC-1.0
      with a high potential of invasion-metastasis after intrapancreatic
      transplantation, were established in a Syrian golden hamster. To determine the
      invasion-metastasis-related factors, a cDNA microarray that represented a set of
      27,000 genes was hybridized with a labeled cDNA probe and screened for molecular
      profiling analysis. Furthermore, Gene Ontology and Pathway differential
      expression of candidate genes was further validated using RT-PCR. One hundred and
      forty-one differentially expressed genes (>3.0-fold change) were identified in
      the present study, including 46 up-regulated genes (e.g., nup107, tjp-2 and MMP
      13) and 95 down-regulated genes (e.g., Spc21, plau and CD44) in the PC-1.0 cells.
      Our present results suggest that a highly organized and structured process of
      tumor invasion-metastasis exists in the pancreas. Analysis of gene expression
      profiles by cDNA microarray provides useful information for clarifying the
      mechanism underlying this invasion and metastasis. Furthermore, the
      identification of invasion-metastasis-specific genes may allow us to develop new
      therapeutic and diagnostic targets for the invasion-metastasis of pancreatic
      cancer.

PMID- 23136618
TI  - Reduced expression of mir15a in the blood of patients with oral squamous cell
      carcinoma is associated with tumor staging.
AB  - MicroRNAs (miRNAs) mir15a and let7a are important regulators of bcl-2, ras and c
      myc proteins. Considering that these miRNAs are commonly altered in many human
      cancers and that these proteins are reported to be altered in oral squamous cell
      carcinoma (OSCC), we investigated them in a set of OSCC cases. The miRNAs as well
      as the proteins were evaluated in the tumor and blood of 20 patients by real-time
      quantitative PCR and immunohistochemistry, respectively. The expression of mir15a
      and bcl-2 proteins in the tumors was not associated with each other or with tumor
      staging. On the other hand, we found reduced expression of this miRNA in the
      blood of patients with an advanced stage of OSCC and with lymph node metastasis.
      The expression of let7a in the tumor and blood was not associated with tumor
      size, lymph node metastasis, tumor staging and immunoexpression of ras and c-myc
      proteins. In conclusion, the present study shows that reduced expression of
      mir15a is associated with OSCC staging.

PMID- 23136619
TI  - Palladium(II)-Catalyzed Regioselective Ortho Arylation of sp(2) C-H Bonds of N
      Aryl-2-amino Pyridine Derivatives.
AB  - The direct arylation of N-(2-pyridyl) substituted anilines is described.
      Arylation takes place in ortho position to the amine functionality and is
      directed by the pyridine N-substituent. Remarkably, N-arylation was never
      observed as a competing process even though conditions also suitable for Buchwald
      Hartwig reactions were applied. The scope of the reaction was investigated in
      terms of aryl donors as well as the electronic nature of the substrate. Good
      yields were obtained for most examples through an operationally simple procedure,
      which did not require inert conditions or even glove box techniques. Pd(OAc)(2)
      was applied as a cheap catalyst and boronic acids as readily available aryl
      donors. To obtain full conversion, 1,4-benzoquinone and a silver salt (e.g.,
      Ag(2)O) were required as additives and reacted at relatively mild temperatures
      (e.g., 80  degrees C). Additionally, the pyridine-directing group was cleaved
      after the reaction to give ortho-arylated aniline derivatives.

PMID- 23136620
TI  - A clinical audit on diabetes care in patients with type 2 diabetes in Al-ain,
      United arab emirates.
AB  - OBJECTIVES: To implement a prospective interventional clinical audit to evaluate
      the current clinical practice and the effect of standard interventions on the
      management of type 2 diabetes (T2DM). METHODS: 254 patients with T2DM where
      recruited in a specialized diabetes care center in Al-Ain, UAE. The diabetes care
      components were audited before (baseline) and after (3 and 6 months)
      implementation of Institute of Clinical System Improvement (ICSI) guidelines.
      Data was compared against international guidelines to achieve target goals of
      normoglycemia, blood pressure (BP), and low density lipoprotein-cholesterol (LDL
      C). We measured changes in mean scores of patient satisfaction level regarding
      diabetes care at similar intervals, by validated Patient Satisfaction
      Questionnaire (PSQ-18). RESULTS: We observed a significant reduction in fasting
      blood glucose (FBG; mean+/- SD; 9.3 +/- 0.03 vs 7.4 +/- 0.3mmol/l; P=0.03), and
      HbA1c (8.7 +/- 0.02 vs 8.1 +/- 0.02 %; P=0.04) levels after 6 months compared
      with baseline. Patients who achieved target FBG and HbA1c levels improved
      significantly (45.7 vs 81.1%; P=0.03), and (40.1 vs 73.6%; P=0.04), respectively.
      The LDL-C levels improved, though this was not statistically significant.
      Patients achieving target of BP control improved significantly (SBP 142+/-7.6 and
      DBP 95+/-6.2 vs SBP 136+/-8.2 and DBP 87+/-5.8 mmHg;P=0.05). CONCLUSIONS: The
      results of this interventional audit were generally positive and emphasized the
      feasibility of improving the current clinical practice. Our individualized
      approach has helped us to achieve a better target in glycemic and BP control as
      well as patient satisfaction. Further research is needed to understand the long
      term impact of our structured approach to improve the quality of T2DM care in the
      UAE.

PMID- 23136621
TI  - Remineralization of eroded enamel lesions by simulated saliva in vitro.
AB  - PURPOSE: The purpose of this study was to evaluate the effects of two simulated
      saliva (SS) remineralization solutions comprising different calcium-inorganic
      phosphate (Ca/P(i)) ratios on eroded enamel. METHODS: 3 mm diameter enamel cores
      were extracted from bovine teeth, mounted in acrylic rods, ground and
      polished,and initially demineralized with either 0.3% (120 minutes) or 1.0% (30
      minutes) citric acid solutions (pH 3.8). Both sets of initially eroded specimens
      were evaluated for surface microhardness (N=10) and treated with either 0.3 or
      1.6 Ca/P(i) ratio SS. Groups were first exposed to a seven-day remineralization
      period and then were cycled in a three-day regimen consisting daily of three
      rounds of two-hour plus overnight SS treatments and three 10-minute static
      immersions in demineralization solution. Specimens were assessed using surface
      microhardness and scanning electron microscopy. RESULTS: Initial erosion from
      0.3% citric acid led to elliptical-shaped pore openings several microns in length
      and in depth and contrasted significantly with respect to 1% citric acid. The
      greatest remineralization was observed from the 0.3 Ca/P(i) SS, while the 1.6
      Ca/P(i) SS produced the least. CONCLUSIONS: This study demonstrated the nature of
      remineralization of eroded enamel depends on both initial erosive conditions and
      the Ca/P(i) ratio of simulated saliva.

PMID- 23136622
TI  - Suppression of neointimal hyperplasia following angioplasty-induced vascular
      injury in pigs infected with swinepox virus.
AB  - Many patients suffering from angina pectoris are treated with percutaneous
      coronary intervention (PCI) and quickly develop angiographic renarrowing, or
      restenosis, at the site of PCI treatment. Restenosis is thought to arise from the
      combinatorial activation of thrombotic and inflammatory responses. The
      inflammatory response responsible for restenosis is also thought to involve the
      activation of a cascade of serine proteases and its subsequent regulation.
      Poxviruses are known to possess a variety of immunomodulatory strategies, some of
      which target serine proteases, cytokines, and chemokines. To this end we
      evaluated whether systemic species-specific swinepox virus (SPV) infection could
      induce sufficient host-immune modulation to promote an anti-inflammatory and anti
      proliferative effect, thereby preventing restenosis. Two groups of domestic
      feeder pigs were used - the first group was experimentally infected with SPV (n=
      11) and the second group served as an uninfected control (n= 5). A week after
      infection, the pigs were anesthetized and percutaneous transluminal coronary
      angioplasty (PTCA) was performed in the left anterior descending coronary artery
      using X-ray fluoroscopy to visualize the balloon and record angiograms. Three
      weeks post infection, the pigs were euthanized and balloon angioplasty injured
      arteries were harvested and examined. We observed a statistically significant
      reduction of restenosis in SPV-infected pigs (p = 0.05) compared to control pigs
      and conclude that systemic swinepox virus infection causes sufficient host immune
      suppression to significantly reduce restenosis in pigs after balloon angioplasty
      injury.

PMID- 23136623
TI  - A Dual Reporter Splicing Assay Using HaloTag-containing Proteins.
AB  - To evaluate the effects of genetic variations on mRNA splicing, we developed a
      minigene-based splicing assay using reporter genes encoding luciferase and the
      multifunctional HaloTag protein. In addition to conventional RT-PCR analysis,
      splicing events can be monitored in this system using two parameters: luciferase
      activity and signals derived from HaloTag-containing proteins bound to a
      fluorescent ligand following SDS-PAGE. The luciferase activity reflects the
      accumulated amounts of successfully spliced HaloTag-luciferase fusion products,
      whereas the amounts and sizes of HaloTag-containing proteins provide quantitative
      insights into precursor, correctly spliced, and aberrantly spliced mRNA species.
      Preliminary experiments confirmed that the dual reporter minigene assay can
      provide estimates of overall splicing efficiency based on the levels of protein
      products. We then used the minigene assay to analyze a case of chronic
      granulomatous disease that was caused by a G>C mutation at position +5 in the 5'
      splice donor site of intron 5 of the CYBB gene. We found that the G>C mutation
      affected CYBB mRNA splicing by changing a delicate balance of splicing
      efficiencies of introns 4, 5, and 6.

PMID- 23136624
TI  - A CMOS In-Pixel CTIA High Sensitivity Fluorescence Imager.
AB  - Traditionally, charge coupled device (CCD) based image sensors have held sway
      over the field of biomedical imaging. Complementary metal oxide semiconductor
      (CMOS) based imagers so far lack sensitivity leading to poor low-light imaging.
      Certain applications including our work on animal-mountable systems for imaging
      in awake and unrestrained rodents require the high sensitivity and image quality
      of CCDs and the low power consumption, flexibility and compactness of CMOS
      imagers. We present a 132*124 high sensitivity imager array with a 20.1 MUm pixel
      pitch fabricated in a standard 0.5 MU CMOS process. The chip incorporates n
      well/p-sub photodiodes, capacitive transimpedance amplifier (CTIA) based in-pixel
      amplification, pixel scanners and delta differencing circuits. The 5-transistor
      all-nMOS pixel interfaces with peripheral pMOS transistors for column-parallel
      CTIA. At 70 fps, the array has a minimum detectable signal of 4 nW/cm(2) at a
      wavelength of 450 nm while consuming 718 MUA from a 3.3 V supply. Peak signal to
      noise ratio (SNR) was 44 dB at an incident intensity of 1 MUW/cm(2). Implementing
      4*4 binning allowed the frame rate to be increased to 675 fps. Alternately,
      sensitivity could be increased to detect about 0.8 nW/cm(2) while maintaining 70
      fps. The chip was used to image single cell fluorescence at 28 fps with an
      average SNR of 32 dB. For comparison, a cooled CCD camera imaged the same cell at
      20 fps with an average SNR of 33.2 dB under the same illumination while consuming
      over a watt.

PMID- 23136625
TI  - Chemoprevention of prostate cancer: soy isoflavones and curcumin.
AB  - The burden of increasing morbidity and mortality due to prostate cancer imposes a
      need for new, effective measures of prevention in daily life. The influence of
      lifestyle on carcinogenesis in Asian men who migrate to Western cultures supports
      a causal role for dietary, environmental, and genetic factors in the epidemiology
      of prostate cancer. Chemoprevention, a prophylactic approach that uses nontoxic
      natural or synthetic compounds to reverse, inhibit, or prevent cancer by
      targeting specific steps in the carcinogenic pathway, is gaining traction among
      health care practitioners. Soy isoflavones and curcumin, staples of the Asian
      diet, have shown promise as functional factors for the chemoprevention of
      prostate cancer because of their ability to modulate multiple intracellular
      signaling pathways, including cellular proliferation, apoptosis, inflammation,
      and androgen receptor signaling. Recent evidence has revealed the DNA damage
      response (DDR) to be one of the earliest events in the multistep progression of
      human epithelial carcinomas to invasive malignancy. Soy isoflavones and curcumin
      activate the DDR, providing an opportunity and rationale for the clinical
      application of these nutraceuticals in the chemoprevention of prostate cancer.

PMID- 23136626
TI  - Influence of nonregional lymph node metastasis as a prognostic factor in
      metastatic prostate cancer patients.
AB  - PURPOSE: In advanced prostate cancer, malignant cells generally tend to spread
      into the bone, and metastasis into nonregional lymph nodes (NRLNs) at the time of
      initial diagnosis is relatively rare. We investigated the prognostic significance
      of NRLN metastasis in patients receiving hormonal therapy and chemotherapy.
      MATERIALS AND METHODS: From February 2005 to August 2011, we identified 105
      patients who had metastatic prostate cancer. First, we assessed the prognostic
      effect of NRLN metastasis on the prostate-specific antigen response through
      logistic regression and the progression-free time to castration-resistant
      prostate cancer (CRPC) by using the Cox proportional hazard regression model.
      Second, we investigated the prognostic influence of NRLN metastasis on the
      chemotherapy response through logistic regression and on cancer-specific survival
      of CRPC patients receiving chemotherapy by using Cox proportional analysis.
      RESULTS: Of these 105 patients, 12 patients (11.4%) had only NRLN metastases
      without bone metastases. Progression-free time to CRPC was significantly less in
      patients with NRLN metastases by Cox proportional hazard regression multivariate
      analysis (p=0.020). However, NRLN metastasis was not an independent factor for
      predicting the response to chemotherapy in CRPC patients, and NRLN metastasis did
      not reduce cancer-specific survival in the multivariate analysis. CONCLUSIONS:
      Twelve (11.4%) of 105 patients with NRLN metastases had lymph node metastases
      without bone metastases. In addition, NRLN metastasis was a significant
      prognostic factor for predicting reduced progression-free time to CRPC. Thus,
      although we speculate that prostate cancer with NRLN metastasis exhibits unique
      tumor biology, additional molecular and genetic studies are needed.

PMID- 23136627
TI  - Changes in Prostate Cancer Aggressiveness over a 12-Year Period in Korea.
AB  - PURPOSE: To investigate whether tumor aggressiveness in patients with prostate
      cancer has changed in Korea since the introduction of prostate-specific antigen
      (PSA) testing. MATERIALS AND METHODS: The data from 2,508 patients with
      pathologically confirmed prostate cancer who underwent radical prostatectomy at
      Asan Medical Center between 2000 and 2011 were reviewed. The patients were
      divided into four 3-year time series, and the changes between the groups in terms
      of serum PSA levels, pathological Gleason score (GS), and pathological stage were
      assessed. The change in GS over time in organ-confined disease and in patients
      whose PSA was below 10 ng/ml was also analyzed. RESULTS: The mean PSA levels
      dropped significantly over the 12-year period (p<0.001). The frequency of organ
      confined disease increased (55.7% vs. 64.7% vs. 62.9% vs. 63.5%, p=0.043). The
      frequency of patients with a GS of 8 or more decreased (38.9% vs. 25.7% vs. 18.2%
      vs. 19.7%) and the frequency of patients with a GS of 6 or less increased (15.0%
      vs. 18.9% vs. 26.7% vs. 18.2%, p=0.003). However, the vast majority (more than
      70%) of all cases had a high GS (7 or greater) at all time points. The GS
      distribution did not change over time in patients whose PSA levels were below 10
      ng/ml or in those who had organ-confined disease. CONCLUSIONS: In 2000 to 2011,
      the preoperative PSA, pathological stage, and pathological GS dropped. However,
      the majority of the prostate cancers in Korean men were poorly differentiated,
      even when the patients had organ-confined disease or their PSA levels were less
      than 10 ng/ml.

PMID- 23136628
TI  - The Prostate Cancer Detection Rate on the Second Prostate Biopsy according to
      Prostate-Specific Antigen Trend.
AB  - PURPOSE: To identify the prostate cancer detection rate on the patients who had
      second prostate biopsy out of the patients who were reported negative in their
      first biopsy. MATERIALS AND METHODS: From July 2006 to February 2012, prostate
      biopsy was performed on 843 patients with over 4 ng/ml and on 618 biopsy negative
      patients PSA was performed from between 6 months and 9 months after biopsy. On
      164 patients, second biopsy was performed, and 42 patients were selected. If
      there was less than 10% change between PSA before the prostate biopsy and PSA
      measured during 6 to 9 months after the first biopsy it was considered as no
      change. If above 10% increase, it was considered increase and if above 10%
      decrease it was considered as decrease. RESULTS: The cancer detection rate in PSA
      increase group was 20%, the detection rate in no change in PSA level but still
      over the normal range group 8.3%, and that in the PSA decrease group was 0%. When
      comparing prostate cancer group and non-cancer group, it is more probable to have
      prostate cancer when they are older, prostate volume is smaller and PSA density
      is higher. CONCLUSIONS: The second biopsy is strongly recommended when PSA level
      shows no change or increase, age is older, prostate volume is smaller or PSA
      density is higher.

PMID- 23136629
TI  - Ultrasound Characteristics of Patients with Urinary Stress Incontinence with or
      without Genital Prolapse.
AB  - PURPOSE: The study purpose was to evaluate the clinical and ultrasound
      characteristics of women with urinary stress incontinence (USI) with or without
      genital prolapse (GP). MATERIALS AND METHODS: A total of 268 patients who
      underwent ultrasound perineal evaluation were divided into two groups: isolated
      USI (n=132) and USIGP (n=136) with USI/GP stage I/II. The latter group was
      additionally divided into two subgroups: USIGP(A) (n=78) with USI/GP stage I and
      USIGP(B) (n=58) with USI/GP stage II. RESULTS: Point Aa (pelvic organ prolapse
      quantification system), which is the projection of the bladder neck (BN) on the
      anterior vaginal wall, was situated higher in the rest position (RP) but moved
      lower during a Valsalva maneuver (VM) in the USI group than in the USIGP group
      (p<0.05). The ultrasound parameters alpha-angle and the distance Sy-BN (symphisis
      bladder neck) decreased, whereas distance H increased, in the USIGP group during
      VM. The ultrasound parameters that gave the best insight into the range of BN
      movements were as follows: distance R->V and angle of rotation (rho), which were
      significantly higher in the USI group than in the USIGP group during VM.
      CONCLUSIONS: According to the clinical and ultrasound findings, we can conclude
      that the BN is situated higher during the RP but moved lower during a VM in
      patients with isolated USI compared with those with concomitant USI/GP, which
      could be explained by the cystocele-immobilizing effect on the BN during the VM
      in the latter group but also by the deteriorated pubo-urethral ligaments in the
      former group.

PMID- 23136630
TI  - Impact of tamsulosin on ureter stone expulsion in korean patients: a meta
      analysis of randomized controlled studies.
AB  - PURPOSE: Using meta-analysis, the study's aim was to evaluate the efficacy of
      tamsulosin, an alpha-blocker, in the treatment of ureteral stones with or without
      shockwave lithotripsy (SWL) in Korean patients. MATERIALS AND METHODS: Relevant
      randomized controlled studies published through June 2011 were identified in a
      search of MEDLINE, KoreaMed, and the Korean Medical Database. No language
      restriction was applied. Only randomized controlled trials conducted with Korean
      patients were eligible for the analysis. The primary outcome assessed was the
      stone clearance rate. Two reviewers independently assessed the quality of the
      study and extracted the data. Meta-analysis was conducted by using R, version
      2.13.0. RESULTS: A total of 6 articles were selected as being suitable for
      evaluation. Pooling of the trials demonstrated a 43% higher expulsion rate for
      tamsulosin treatment compared to a control group (risk ratio [RR], 1.43; 95%
      confidence interval [CI]: 1.24 to 1.65). Similar results were obtained in all
      subgroup analyses according to stone location (upper: RR, 1.31; 95% CI, 1.02 to
      1.68, lower: RR, 1.50; 95% CI, 1.20 to 1.88) or concomitant SWL (yes: RR, 1.38;
      95% CI, 1.14 to 1.68, no: RR, 1.48; 95% CI, 1.21 to 1.83). CONCLUSIONS: This meta
      analysis of randomized controlled studies provides a high level of evidence
      supporting the suggestion that treatment with tamsulosin augments the stone
      expulsion rate for ureter stones with or without SWL in a Korean population.
      However, a high-quality, large-scale, multicenter, randomized controlled trial is
      warranted to fully support this hypothesis.

PMID- 23136631
TI  - Effects of Carthamus tinctorius on Semen Quality and Gonadal Hormone Levels in
      Partially Sterile Male Rats.
AB  - PURPOSE: Traditional herbal medicine is just one of the many different approaches
      using plants in the remedy of diseases. Carthamus tinctorius (CT) or safflower is
      a popular plant that is used for coloring and flavoring in food industries. The
      effect of CT on spermatogenesis and sperm parameters has been reported in
      traditional medicine but has not yet been confirmed scientifically. Therefore,
      this study was designed to determine the effects of CT on spermatogenesis and the
      male reproductive system in an animal model. MATERIALS AND METHODS: Sixty male
      rats were divided into five groups. Four groups were injected with 5 mg/kg of
      busulfan as a model of partial infertility. Then, the experimental groups were
      treated with 10 mg/kg, 25 mg/kg, or 50 mg/kg of CT extract for 35 days. The
      control was treated with busulfan (infertile control) or distilled water only.
      After this period, the animals were sacrificed and blood samples were taken for
      hormonal assay. The semen was collected from the epididymis and the reproductive
      organs were assessed. Sperm count and motility were measured and smears were
      prepared for assessment of the other parameters. RESULTS: The results indicated
      that the percentage of sperm with good morphology, motility, and count increased
      significantly in the group treated with 10 mg/kg CT (p=0.002, p=0.03, and
      p=0.00001, respectively). The effects on hormonal changes and genital organ
      weights were also positive. CONCLUSIONS: It is probable that the CT extract
      affects spermatogenesis and as a result sperm quality. Further studies are
      needed.

PMID- 23136632
TI  - Risk factors for the development of urethrocutaneous fistula after hypospadias
      repair: a retrospective study.
AB  - PURPOSE: The purpose of this study was to investigate the risk factors for
      urethrocutaneous fistula development after hypospadias repair. MATERIALS AND
      METHODS: Between January 1990 and May 2010, 348 patients underwent hypospadias
      repair. This study included 294 patients who were followed up for more than 6
      months. Potential risk factors for the development of fistula after operation
      included age, location of hypospadias, type of hypospadias repair, suture
      materials and methods, methods and duration of catheterization, combined
      congenital urologic disorders, timing of presentation and repair of fistula, and
      location of fistula. Data were analyzed retrospectively. Binary logistic
      regression analysis was used for univariate and multivariate analysis. RESULTS:
      Out of 294 patients, 63 patients (21.4%, 63/294) developed urethrocutaneous
      fistulas after hypospadias repair. In the univariate analysis, fistula formation
      was statistically related with type of hypospadias and type of hypospadias
      repair. In the multivariate analysis with stratification by hypospadias site,
      however, only the location of hypospadias was a significant independent risk
      factor in urethrocutaneous fistula development after hypospadias repair
      (p<0.001). CONCLUSIONS: Our results suggest that the risk of developing
      urethrocutaneous fistula after hypospadias repair is associated with the location
      of hypospadias (more proximal-type hypospadias). Type of hypospadias repair,
      suture materials, suture techniques, and number of other combined urologic
      disorders were not related to the development of urethrocutaneous fistulas.

PMID- 23136633
TI  - Abnormal dimercaptosuccinic Acid scan may be related to persistence of
      vesicoureteral reflux in children with febrile urinary tract infection.
AB  - PURPOSE: This study assessed whether (99m)technetium dimercaptosuccinic acid
      (DMSA) scintigraphy used for the assessment of renal sequelae after febrile
      urinary tract infection (UTI) has any prognostic value for outcome measurement of
      vesicoureteral reflux (VUR) by retrospectively evaluating the correlation between
      abnormal DMSA scintigraphy results and persistence of VUR in children with
      febrile UTI. MATERIALS AND METHODS: The medical records of 142 children (57 boys,
      85 girls) admitted with febrile UTI from January 2004 to December 2006 and who
      were followed up for more than 1 year were retrospectively reviewed. At the
      initial and follow-up visits, renal ultrasound and DMSA scans were performed
      within 7 days from the diagnosis and voiding cystourethrography (VCUG) was
      performed within 1 month in all case and follow-up evaluations. RESULTS: The
      children's mean age was 4.8+/-3.6 years (range, 0.3 to 14 years). The mean follow
      up was 28.2+/-4.8 months. At the initial examination, VUR was more often
      associated with an abnormal DMSA scan result (83.3%) than with a normal DMSA scan
      result (16.7%, p=0.02). The frequency of VUR with an abnormal DMSA scan during
      acute UTI was significantly higher than the frequency of VUR with a normal DMSA
      scan (38.8% vs, 25.8%, respectively, p=0.004). Also, high-grade VUR was
      associated with an abnormal DMSA scan result (32.5%) more often than with a
      normal DMSA scan result (0%, p=0.01). Children with an abnormal DMSA scan had a
      lower resolution rate of VUR (17.5%) than did children with a normal DMSA scan
      (75.0%) at the follow-up VCUG (p=0.02). CONCLUSIONS: An abnormal result on a DMSA
      scan during febrile UTI is associated with high-grade and persistent VUR. DMSA
      scans performed during febrile UTI are useful in reflux resolution in childhood.

PMID- 23136634
TI  - Clinical Assessment of Follow-Up Cystatin C-Based eGFR in Live Kidney Donors.
AB  - PURPOSE: We aimed to compare the cystatin C-based estimated glomerular filtration
      rate (eGFR) and the serum creatinine-based eGFR and to investigate the clinical
      roles of the cystatin C-based eGFR in assessing the follow-up renal function of
      kidney donors. MATERIALS AND METHODS: We enrolled 121 healthy kidney donors who
      underwent live donor nephrectomy between October 2009 and December 2010 in a
      prospective manner. Serum creatinine and cystatin C were measured preoperatively
      and were followed after the surgery (1st, 4th, and 7th postoperative day and 1st,
      3rd, 6th, and 12th postoperative month). We also compared the sensitivity and
      specificity of each eGFR method for predicting the development of chronic kidney
      disease (CKD) after donor nephrectomy. RESULTS: For those who had a Modification
      of Diet in Renal Disease postoperative day 4 eGFR of less than 60 ml/min/1.73
      m(2), the probability of developing CKD was 89.0% (Chronic Kidney Disease
      Epidemiology Collaboration eGFR, 66.0%; Cockcroft-Gault eGFR, 74.0%; cystatin C
      eGFR, 57.1%). A cystatin C eGFR of below 60 ml/min/1.73 m(2) at postoperative day
      4 predicted CKD at 6 months with a specificity of 90.3%, which was the highest
      among the estimation methods used. Cystatin C eGFRs were generally higher than
      the creatinine-based eGFRs. CONCLUSIONS: We conclude that cystatin C-based
      estimations of the GFR are helpful for predicting the recovery of renal function
      in kidney donors and could be added to the follow-up protocol of kidney donors
      who may develop CKD, especially patients whose immediate postoperative renal
      function is marginal.

PMID- 23136635
TI  - Synergistic effect of mesenchymal stem cells infected with recombinant adenovirus
      expressing human BDNF on erectile function in a rat model of cavernous nerve
      injury.
AB  - PURPOSE: To evaluate the combined role of mescenchymal stem cells (MSCs) infected
      with recombinant adenoviruses expressing human BDNF (rAd/hBDNF) on the erectile
      dysfunction in rat with cavernous nerve injury. MATERIALS AND METHODS: Rats
      divided into 4 groups: control group, bilateral cavernous nerve crushing group
      (BCNC group), BCNC with MSCs group and BCNC with MSCs infected with rAd/hBDNF
      group. After 4-week, functional assessment was done. PKH26 and BDNF staining of
      major pelvic ganglion and masson's trichrome staining of corpus cavernosum were
      performed. Western blot analysis of endothelial nitric oxide synthase (eNOS) and
      neuronal nitric oxide synthase (nNOS) was done in corpus cavernosum. RESULTS:
      After 4 weeks, BCNC with MSCs and MSCs infected with rAd/hBDNF groups showed
      significantly well-preserved erectile function compared with BCNC group.
      Moreover, the erectile function of MSCs infected with rAd/hBDNF group was
      significantly well-preserved than BCNC with MSCs group. The smooth muscle of
      corpus cavernosum was significantly preserved in BCNC with MSCs and MSCs infected
      with rAd/hBDNF groups compared with BCNC group. More preservation of smooth
      muscle was observed in rats with MSCs infected with rAd/hBDNF than with MSCs
      alone. Significant increase expression of eNOS and nNOS was noted in rats with
      MSCs infected with rAd/hBDNF than with MSCs alone. CONCLUSIONS: The erectile
      function was more preserved after injection with MSCs infected with rAd/hBDNF in
      rat with ED caused by cavernous nerve injury. Therefore, the use of MSC infected
      with rAd/hBDNF may have a better treatment effect on ED cause by cavernous nerve
      injury.

PMID- 23136636
TI  - Primary undifferentiated penile sarcoma in adolescence.
AB  - We report a case of primary penile undifferentiated sarcoma. A 16-year-old
      adolescent man visited Pusan National University Hospital complaining of a
      painless mass on his penis that was increasing in size. Magnetic resonance images
      revealed a 5*5-cm mass and pathological examinations revealed small round cell
      sarcomas with neuroendocrine differentiation. The tumor, which had metastatic
      pulmonary nodules, was treated by tumorectomy and systemic chemotherapy. Thirty
      four months after the initial diagnosis, the patient was still alive without
      evidence of local recurrence or metastatic disease. This is our second case of an
      undifferentiated penile sarcoma.

PMID- 23136637
TI  - Tubal Buccal Mucosa Graft without Anastomosis of the Proximal Urethra for Long
      Segment Posterior Urethral Defect Repair.
AB  - A 31-year-old man was referred for further management of a urethral stricture. He
      was a victim of a traffic accident and his urethral injury was associated with a
      pelvic bone fracture. He had previously undergone a suprapubic cystostomy only
      owing to his unstable general condition at another hospital. After 3 months of
      urethral injury, direct urethral anastomosis was attempted, but the surgery
      failed. An additional 4 failed internal urethrotomies were performed before the
      patient visited Chungbuk National University Hospital. Preoperative images
      revealed complete posterior urethral disruption, and the defect length was 4 cm.
      We performed a buccal mucosa tubal graft without anastomosis of the proximal
      urethra for a long segment posterior urethral defect. The Foley catheter was
      removed 3 weeks after the operation and the patient was able to void
      successfully. After 8 months, he had normal voiding function without urinary
      incontinence.

PMID- 23136638
TI  - Multiple shoot induction from axillary bud cultures of the medicinal orchid,
      Dendrobium longicornu.
AB  - BACKGROUND AND AIMS: Dendrobium longicornu, commonly known as the 'Long-horned
      Dendrobium', is an endangered and medicinally important epiphytic orchid. Over
      exploitation and habitat destruction seriously threaten this orchid in Northeast
      India. Our objective was to develop an efficient protocol for the mass
      propagation of D. longicornu using axillary bud segments. METHODOLOGY AND
      PRINCIPAL RESULTS: Axillary buds cultured in Murashige and Skoog semi-solid
      medium supplemented with alpha-naphthalene acetic acid (NAA), 2,4-dichlorophenoxy
      acetic acid (2,4-D) and 6-benzylaminopurine (BAP) readily developed into
      plantlets. These formed either directly from shoot buds or from intermediary
      protocorm-like bodies (PLBs). The maximum explant response (86.6 %) was obtained
      in medium supplemented with NAA at 30 uM, while the maximum number of shoots
      (4.42) and maximum bud-forming capacity (3.51) were observed in medium containing
      15 uM BAP and 5 uM NAA in combination. Protocorm-like bodies were obtained when
      the medium contained 2,4-D. The maximum number of explants forming PLBs (41.48 %)
      was obtained in medium containing 15 uM BAP and 15 uM 2,4-D. Well-developed
      plantlets obtained after 20-25 weeks of culture were acclimatized and eventually
      transferred to the greenhouse. Over 60 % of these survived to form plants ~3-4 cm
      tall after 90 days in glasshouse conditions using a substrate of crushed brick
      and charcoal, shredded bark and moss. CONCLUSIONS: The method described can
      readily be used for the rapid and large-scale regeneration of D. longicornu. Its
      commercial adoption would reduce the collection of this medicinally important and
      increasingly rare orchid from the wild.

PMID- 23136639
TI  - Fruit transpiration in kiwifruit: environmental drivers and predictive model.
AB  - BACKGROUND AND AIMS: In most fruit crops, storage quality varies greatly between
      regions and seasons, causing significant commercial loss. Understanding the
      sources of this variability will contribute to the knowledge of fruit
      developmental physiology and may also benefit commercial fruit production via
      altered managements that reduce it or forecasts that predict it. A causal-chain
      relationship is proposed to help elucidate the sources of variability in fruit
      storage quality: the weather ->(i)-> fruit transpiration ->(ii)-> fruit calcium 
      >(iii)-> fruit storage quality. This paper explores the first link of this
      hypothesis, ->(i)->, for Hayward kiwifruit using field measurements of fruit
      transpiration rate and concurrent meteorological recordings. The aims are to
      identify the key environmental variables driving fruit transpiration and develop
      a predictive fruit transpiration model. METHODOLOGY: Fruit transpiration was
      determined hourly over several 24-h periods by recording weight loss of detached
      fruit, on Days 23, 35, 49, 65, 94 and 140 after full bloom. Meteorological
      records were made every 15 min throughout the season at an adjacent regional
      weather station. A model of fruit transpiration was developed in which the usual
      meteorological variables (radiation, temperature, windspeed and relative
      humidity) were incorporated in a Fick's Law transpiration flux equation.
      PRINCIPAL RESULTS: Fruit transpiration rate (i.e. the molar flux density, mmol
      cm(-2) h(-1)) varied diurnally and decreased during the season. The dominant
      fruit variable governing transpiration rate was skin conductance and the dominant
      environmental variables were relative humidity and temperature. Radiation and
      windspeed were not significantly influential. CONCLUSIONS: The model provides a
      good fit to the fruit transpiration rate measurements regardless of the time of
      day/night or the stage of fruit development. The model allows reasonably accurate
      and continuous predictions of fruit transpiration rate throughout fruit
      development based on standard meteorological recordings. It also allows estimates
      of cumulative fruit transpiration throughout the season.

PMID- 23136640
TI  - Fluorescence laser microdissection reveals a distinct pattern of gene activation
      in the mouse hippocampal region.
AB  - A histoanatomical context is imperative in an analysis of gene expression in a
      cell in a tissue to elucidate physiological function of the cell. In this study,
      we made technical advances in fluorescence laser microdissection (LMD) in
      combination with the absolute quantification of small amounts of mRNAs from a
      region of interest (ROI) in fluorescence-labeled tissue sections. We demonstrate
      that our fluorescence LMD-RTqPCR method has three orders of dynamic range, with
      the lower limit of ROI-size corresponding to a single cell. The absolute
      quantification of the expression levels of the immediate early genes in an ROI
      equivalent to a few hundred neurons in the hippocampus revealed that mice
      transferred from their home cage to a novel environment have distinct activation
      profiles in the hippocampal regions (CA1, CA3, and DG) and that the gene
      expression pattern in CA1, but not in the other regions, follows a power law
      distribution.

PMID- 23136641
TI  - Radiation-suppressed plasmonic open resonators designed by nonmagnetic
      transformation optics.
AB  - How to confine light energy associated with surface plasmon polaritons (SPPs) in
      a physical space with minimal radiation loss whereas creating maximum interacting
      section with surrounding environment is of particular interest in plasmonic
      optics. By virtue of transformation optics, we propose a design method of forming
      a polygonal surface-plasmonic resonator in fully open structures by applying the
      nonmagnetic affine transformation optics strategy. The radiation loss can be
      suppressed because SPPs that propagate in the designed open structures will be
      deceived as if they were propagating on a flat metal/dielectric interface without
      radiation. Because of the nonmagnetic nature of the transformation strategy, this
      design can be implemented with dielectric materials available in nature. An
      experimentally verifiable model is subsequently proposed for future experimental
      demonstration. Our design may find potential applications in omnidirectional
      sensing, light harvesting, energy storage and plasmonic lasing.

PMID- 23136642
TI  - Assessment of asthma control and asthma exacerbations in the epidemiology and
      natural history of asthma: outcomes and treatment regimens (TENOR) observational
      cohort.
AB  - Patients with severe or difficult-to-treat asthma account for substantial asthma
      morbidity, mortality, and healthcare burden despite comprising only a small
      proportion of the total asthma population. TENOR, a multicenter, observational,
      prospective cohort study was initiated in 2001. It enrolled 4,756 adults,
      adolescents and children with severe or difficult-to-treat asthma who were
      followed semi-annually and annually for three years, enabling insight to be
      gained into this understudied population. A broad range of demographic, clinical,
      and patient self-reported assessments were completed during the follow-up period.
      Here, we present key findings from the TENOR registry in relation to asthma
      control and exacerbations, including the identification of specific subgroups
      found to be at particularly high-risk. Identification of the factors and
      subgroups associated with poor asthma control and increased risk of exacerbations
      can help physicians design individual asthma management, and improve asthma
      related health outcomes for these patients.

PMID- 23136643
TI  - Quantification by SIFT-MS of acetaldehyde released by lung cells in a 3D model.
AB  - Our previous studies have shown that both lung cancer cells and non-malignant
      lung cells release acetaldehyde in vitro. However, data from other laboratories
      have produced conflicting results. Furthermore, all these studies have been
      carried out in 2D models which are less physiological cell growth systems when
      compared to 3D models. Therefore, we have carried out further work on the release
      of acetaldehyde by lung cells in 3D collagen hydrogels. Lung cancer cells CALU-1
      and non-malignant lung cells NL20 were seeded in these hydrogels at different
      cell concentrations and the release of acetaldehyde was measured with the
      Selected Ion Flow Tube Mass Spectrometry (SIFT-MS) technique. The data obtained
      showed that the amount of acetaldehyde released by both cell types grown in a 3D
      model is higher when compared to that of the same cells grown in 2D models. More
      importantly, acetaldehyde from the headspace of lung cancer cells could be
      measured even at a low cell concentration (10(5) cells per hydrogel). The
      differential of acetaldehyde release could be, depending on the cell
      concentration, more than 3 fold higher for cancer cells when compared to non
      malignant lung cells. This pilot study is the first to study acetaldehyde
      emission from albeit only two cell types cultured in 3D scaffolds. Clearly, from
      such limited data the behaviour of other cell types and of tumour cells in vivo
      cannot be predicted with confidence. Nevertheless, this work represents another
      step in the search for volatile biomarkers of tumour cells, the ultimate goal of
      which is to exploit volatile compounds in exhaled breath and other biological
      fluids as biomarkers of tumours in vivo.

PMID- 23136644
TI  - [Does the Medical Doctor's Pension Fund diagnose multiple sclerosis correct?].

PMID- 23136645
TI  - [Cancer packages: Haste does not make waste!].

PMID- 23136646
TI  - Murky manoeuvres.

PMID- 23136647
TI  - Bad press.

PMID- 23136648
TI  - Fight the power.

PMID- 23136649
TI  - Autism.

PMID- 23136650
TI  - Epidemiology: Complex disorder.

PMID- 23136651
TI  - Genetics: Searching for answers.

PMID- 23136652
TI  - Child development: The first steps.

PMID- 23136653
TI  - Adulthood: Life lessons.

PMID- 23136654
TI  - Diagnosis: Redefining autism.

PMID- 23136655
TI  - Perspective: Imaging autism.

PMID- 23136656
TI  - Culture: Diverse diagnostics.

PMID- 23136657
TI  - Perspective: Brain scans need a rethink.

PMID- 23136658
TI  - Treatments: In the waiting room.

PMID- 23136659
TI  - Gelatinous transformation.

PMID- 23136660
TI  - Lost in translation: misfolded proteins may cause neurodegeneration by inhibiting
      normal protein production.

PMID- 23136662
TI  - [High performance sport - medical preliminary examinations in children make
      sense].

PMID- 23136661
TI  - The external globus pallidus: much more than an inhibitory relay of the indirect
      pathway.

PMID- 23136663
TI  - [Achilles tendinopathy - doppler signal decreased after exercise].

PMID- 23136664
TI  - [Achilles tendinopathy - does eccentric training support the laser?].

PMID- 23136665
TI  - [Hip osteoarthritis - hip resurfacing allows return to running training].

PMID- 23136666
TI  - [Nonspecific back pain - who benefits from Pilates?].

PMID- 23136667
TI  - [Doping - calf hemodialysate do not give more power].

PMID- 23136668
TI  - [Prospective multicenter comparison - Orthopedics: dumb and strong?].

PMID- 23136669
TI  - David Sumpter.

PMID- 23136670
TI  - The ancestor's paunch.

PMID- 23136671
TI  - Rapid population rise bad for our health?

PMID- 23136688
TI  - [Epilepsy].

PMID- 23136687
TI  - [Seeking a technical innovation in medical psychiatry].

PMID- 23136690
TI  - [Genetic study of schizophrenia-focusing on GWAS-].

PMID- 23136689
TI  - [Symptom of depression and bipolar disorder in Japan population-focus on job
      related anxiety].

PMID- 23136691
TI  - A day off in Denmark.

PMID- 23136692
TI  - [Kampo pharmacology: pharmacological evidence as a complementary and alternative
      medicine].

PMID- 23136693
TI  - [Medial subtalar dislocation in a young amateur football player].

PMID- 23136694
TI  - [Q & A. A raised lesion of the gastric antrum with a tendency to increase in
      size].

PMID- 23136695
TI  - [Regulatory mechanism of glycolipid metabolism by bone tissue].

PMID- 23136696
TI  - [Aiming for improvement in the safety of medical care].

PMID- 23136697
TI  - [The M-cycle of crime].
AB  - Crime development measured by means of the changes in police recorded crime
      statistics (criminal offences per 100.000 inhabitants) shows periodical cycles,
      which can be described by the capital letter M. Starting from a low rate of
      criminality, crime rises over 1-3 years followed by an interim decline lasting
      for about one year. Then crime increases again for approximately 2 years to a
      second peak. After that, crime strongly declines to the next low point over a
      period of about two years. The course of this development is not uniform with
      equal amplitudes, but resembles an M-curve. Since 1950, seven such M-cycles have
      been observed with the 3rd M-cycle from 1965-1973, the 4th M-cycle from 1973
      1984, the 5th M-cycle from 1984-1994, the 6th M-cycle from 1994-2005 and the 7th
      M-cycle from 2005-2010 being particularly distinct. The M-curve of crime may be
      explained by the M-form of the business cycle. Since World War II, the M-cycle of
      crime and the M-cycle of the economy have run approximately parallel. Up to the
      first large oil crisis, the M-cycle of crime preceded the economic situation by 1
      2 years, whereas since 1976 it has followed the economic development with a time
      lag of one to two years.

PMID- 23136698
TI  - [Physical and gynecological examinations in female victims of sexual violence
      with special emphasis on crime-reporting behaviour].
AB  - Sexual abuse of females is a common form of violence with a high dark figure.
      While part of the victims decide to report the event to the police, many women
      are embarrassed to do so for a number of reasons. Retrospectively, examinations
      performed in Berne (Switzerland) between 2006 and 2008 in cases with and without
      report to the police were analyzed. Altogether, 207 examinations were carried out
      during that period (65.2% reported to the police, 34.8% without report to the
      police). 20% of the incidents were reported to the police after the examination.
      One third of the victims in both groups claimed that the perpetrator was unknown
      to them. More than 40% of the women in both groups had been under the influence
      of alcohol at the time of the incident. 73% of the victims (reporting the crime)
      and 61% of those not filing a crime report described penile-vaginal contacts.
      Blackouts were claimed in 14% of the cases reported to the police and 33% of
      those not reported. Genital lesions were found in about one third and
      extragenital injuries in more than 50% of cases in both groups. No condom had
      been used in a large percentage of cases or its use was uncertain. Unprotected
      vaginal ejaculation was reported by about one third of the victims in both groups
      and could not be reliably excluded in 28% of cases. In 43.8% (reported to police)
      and 47.1% (not reported), no contraceptive method had been applied by the women.
      The results of the present study show similar distributions in both groups for
      numerous factors (factual circumstances and injury pattern). However, in the
      group not filing a complaint with the police blackouts were reported more often,
      which may have induced the victims not to report the incident to the police at
      first. The fact that in about 20% of these cases the women went to the police
      later underlines the importance of offering documentation usable as evidence in
      court and preserving evidence independent of whether the incident has already
      been reported to the police or not. Reasons why victims present for examination
      may also be fear of pregnancy or sexually transmitted diseases. Clarification of
      these points should therefore also be offered.

PMID- 23136699
TI  - [The querulant--troublesome or dangerous?].
AB  - Querulants are a considerable problem for the legal system. Although they do not
      break the law at first, they want to enforce their point of view in legal
      conflicts with their environment at any cost. If they cannot win their case in
      court, they often prove to be uncontrollable and continue their fight no matter
      what it takes, sometimes until their financial means are exhausted. Because they
      often have a paranoid personality structure, they then feel victimised by corrupt
      judges and the escalation spiral tends to go on without end. In extreme cases,
      this may even lead to massive violent actions against their opponents. The author
      presents a case report of such a deadly escalation.

PMID- 23136700
TI  - [Influence of grave chamber systems on decomposition].
AB  - Grave chambers allow bodies to decompose independent of hydrogeological
      circumstances. We examined the degree of body decomposition in 11 grave chambers
      after burial times between 12.1 and 15.3 years (mean 13.0 years). In 8 of the
      examined 11 bodies, bones were separated due to complete loss of tissue
      continuity. In 3 cases, the graves were partly not properly constructed and
      tissue continuity was at least partially preserved. Biochemical estimation of the
      age at the time of death on the basis of six teeth gathered during the inspection
      of the grave chambers showed only one result that could not be explained by the
      standard deviation of the method used.

PMID- 23136701
TI  - [Definition of a "domestic-setting corpse"--a retrospective study of 211
      discoveries].
AB  - In Germany, the term "domestic-setting corpse" is regularly used both in the
      medicolegal field (daily work, specialist literature) and by the general public
      (press, novels). The only formal definition of the term is in the German-language
      textbook "Basiswissen Rechtsmedizin" (Madea and Dettmeyer 2007). In this
      retrospective study, we compared the criteria for this definition with our
      findings. Autopsy reports from the Institute of Forensic Medicine at the Justus
      Liebig University in Giessen, Germany, for the period between 2005 and 2011
      (including February), were reviewed retropectively to see if the criteria for
      this formal definition could be found. We chose a postmortem interval of more
      than 24 hours and discovery of the corpse in a private home as inclusion criteria
      for our study (n = 211). We could verify four of the criteria for the definition
      ("advanced signs of decomposition", "reclusiveness", "unclear cause of death",
      "difficult to identify") in our study. One criterion ("frequently a long
      postmortem interval") was too vague to be of use, and two further criteria
      ("discovery circumstances" and "high frequency of active alcohol dependence")
      could only be partially confirmed. In almost half of our cases there were,
      however, signs of general substance abuse. The proportion of male "domestic
      setting corpses" was distinctly higher than that of females (approx. 3:1). The
      average age-at-death was 50.1 years for men, and 57.8 years for women, and thus
      clearly below the average life expectancies. In over half of the cases - even
      those with explicitly mentioned advanced facial decay--the identification method
      had not been noted. In the formal definition, the criteria "discovery
      circumstances" and "alcoholism" thus need to be more precisely defined. Also, due
      to the inexplicit time range, the criterion "frequently a long postmortem
      interval" was too vague to be applied to, or compared with, our cases as a
      classic criterion. We suggest specifying a minimum postmortem interval of 24
      hours for "domestic-setting corpses". In addition, more attention should be paid
      to the identification of "domestic-setting corpses". To date, investigation
      authorities frequently seem to assume that a corpse discovered in a private
      residence is that of the home owner or occupant.

PMID- 23136702
TI  - [Positional asphyxia--death in a head-down position after falling down stairs].
AB  - The discovery of a body in an unusual position such as a head-down position
      requires thorough investigation. In this article, such a death is reported. A 64
      year-old man was found in a head-down position at the bottom of a narrow
      staircase after obviously falling down the stairs. His head was wedged between
      the last step and a closed sliding door. Autopsy revealed craniofacial blunt
      force injuries, a non-dislocated fracture of the 4th cervical vertebral body
      (with intact ligaments of the spine and cervical cord) and massive cerebral and
      pulmonary oedema. Although the heart was significantly enlarged (610 g), the
      coronary arteries showed only minor arteriosclerotic changes. The alcohol
      concentration measured was 2.06 per mil in blood and 2.67 per mil in urine. The
      alcohol intoxication increased the risk to fall and together with the trauma of
      the cervical spine made it impossible for the man to free himself so that he
      ultimately died in a head-down position.

PMID- 23136703
TI  - Factors contributing to non-adherence to diabetes treatment among diabetic
      patients attending clinic in Mwanza city.
AB  - BACKGROUND: Non-adherence to the diabetes treatment regimen is possibly the most
      common reason for poor health outcomes among people with diabetes. The rates of
      non-adherence to diabetes regimen tasks are highly variable, but have significant
      consequences on diabetes outcomes and the effectiveness of treatments. OBJECTIVE:
      The aim of this study was to determine the proportion (magnitude) of non
      adherence and its contributing factors among diabetic patients attending clinics
      in Mwanza city. Specifically the study determined the relationship between non
      adherence and various variables which are; alcohol use, knowledge on diabetes,
      its treatment and complication, travel distance to reach the clinic by patients
      and medication side effects. RESULTS: A total of 272 diabetic patients attending
      two diabetes clinics in Mwanza city were interviewed. Of the respondents, 118
      (43.4%) were males. Their mean age was 51.22 (14.97 standard deviation). Among
      all respondents, 255 (93.8%) scored High level of knowledge on Diabetes and its
      treatment as compared with those with low knowledge making it not a significant
      contributor to non-adherence. Of the 272 patients, 77 (28.3%) reported non
      adherent. Alcohol use, medication side effects and distance travelled to reach
      the clinic were the significant contributors to non-adherence (p = 0.001).
      CONCLUSION: Factors which were found contributing to non-adherence to diabetes
      treatment include: alcohol use, medication side effects and few clinics located
      far from most of patient. For improving adherence, availability of information
      with patients' perspectives about patients' expectations, needs and experiences
      in taking medication and about what might help them to become and remain adherent
      should be maintained.

PMID- 23136704
TI  - Association between anaemia and infections (HIV, malaria and hookworm) among
      children admitted at Muhimbili National Hospital.
AB  - OBJECTIVE: Anaemia is the major cause of morbidity and mortality in paediatric
      age with much aetiology. The magnitude of childhood anaemia has been inadequately
      studied at Muhimbili National Hospital (MNH). The study was aimed at determining
      the frequency of anaemia and associated infections in patients admitted in
      general paediatric wards at MNH in Dar es Salaam. METHODS:  STUDY DESIGN: This
      was a descriptive cross-sectional study. STUDY SETTING: This was conducted at MNH
      in general paediatric wards from 20th August, 2009 to 15th December, 2009.
      SUBJECTS: Patients, aged 1-84 months, consecutively admitted were recruited in
      the study. After informed verbal consent from the guardian or parent was
      obtained, information on demographic and clinical characteristics was collected
      from the parent or guardian. Physical examination and laboratory tests on blood ;
      stool samples for hookworm screening; blood slides for malaria parasites; Human
      Immunodeficiency Virus (HIV) screening; and blood peripheral smears were done on
      all subjects. Additional information was taken from medical files. Data
      management: The prevalence of anemia was determined as a percentage of all
      paediatric patients recruited during the time of data collection. All information
      was recorded using questionnaires and analysis was done using SPSS version 13.0.
      A p value of < 0.05 was considered statistically significant. RESULTS: A total of
      315 children were assessed. The frequency of anaemia was 79.4%. This is much
      higher than the WHO prevalence of 67.6% in Africa for anaemia to be taken as a
      disease of public health importance. The proportion of malaria was 7.9%, HIV
      seropositive was 10.2% and hookworm was 1.0% of all admissions. There was an
      increased risk of anaemia in patients with HIV seropositive and or malaria
      although this was not statistically significant (RR > 1.0, p > 0.05). CONCLUSION:
      Anaemia in paediatric patients admitted at MNH is a disease of high public health
      importance in Dar es Salaam and may well carry a high burden in the rest of the
      country. Other risk factors of anaemia should be investigated with a goal of
      reducing the burden of anaemia.

PMID- 23136705
TI  - Antiretroviral drug adherence by HIV infected children attending Kericho District
      Hospital, Kenya.
AB  - OBJECTIVE: To determine ARV drug adherence levels in children (aged 3 to 14
      years) attending Kericho District Hospital (KDH), Kenya. METHODS: A cross
      sectional design was used to collect data from a random sample of caregivers of
      230 children on ARVs for a study period of six months (i.e. 1st August 2010 to
      31st January 2011). The study population comprised HIV infected children on ARVs
      and their caregivers. The caregivers whose children met the selection criteria
      were selected. A structured pre-tested, interviewer-administered questionnaire
      was used to interview the caregivers of the HIV infected children who were
      selected from among those who took the children for treatment. The interview was
      continued on the consecutive caregivers until the sample of 230 children was
      attained. The key variables examined were; demographic information of caregivers
      and children and drug adherence levels. Measures of adherence included; drug/pill
      counting and estimate of volumes of syrup remaining from the last prescription,
      caregiver reports (on keeping clinic appointments and timing of taking ARVs by
      the child), and drug refill data (from pharmacy records). Data was analyzed using
      SPSS version 12.0.1 with statistical significance set at P < 0.05. RESULTS: The
      adherence levels based on time of taking ARV drugs was 56.1%, keeping clinic
      appointments 45.7%, No ARVs returned (i.e. took all drugs assessed through pill
      counts) 27%, and pharmacy drug refill was 47.8%. The overall average adherence
      level was suboptimal at 44.2%. It was recommended that caregivers of the HIV
      infected children should be educated on importance of strict adherence to
      prescribed doses of ARVs to the children. Future research should explore using
      multiple measures of adherence and reasons for non-adherence among HIV infecting
      children. CONCLUSION: The drug adherence level was sub-optimal.

PMID- 23136706
TI  - Trends and determinants of condom use in Uganda.
AB  - BACKGROUND: Condom use is an integral indicator of risky sexual behaviour and, as
      a result, is a potential predictor of future HIV infection rates. Consequently,
      documenting trends in condom use and exploring the factors associated with their
      utilisation are important for broadening the information base for the design of
      HIV intervention programmes. This paper aims to document Uganda's nationwide
      trends in condom use from 1995 to 2006 and seeks to understand some of the socio
      demographic variables that may be associated with their use, using Uganda
      Demographic Health Surveys (UDHS). METHOD: Data from the Uganda Demographic
      Health Surveys (UDHS) conducted in 1995, 2000/2001 and 2006 were analysed.
      Sociodemographic variables as well as 'Year of the survey' were selected to
      assess their interaction with condom use. Multivariate regression analyses were
      performed. Odds Ratios and Confidence Intervals were computed. RESULTS: Certain
      socio-demographic factors such as being male and living in an urban setting are
      significantly associated with an increased likelihood of using condoms than
      others. All results indicate a far greater increase in condom use between 1995
      and 2000/2001 compared to the rate of increase in condom use from 2000/2001 to
      2006. CONCLUSION: Policies need to address the lowered use of condoms amongst
      women and rural populations. The wane in increase in condom use between 2000/2001
      and 2006 may be the result of interrupted distribution of condoms between 2004
      and 2006. However, this may also be due to the large-scale influx of
      antiretrovirals (starting in 2004) which may be lowering the anxiety associated
      with the social construct of HIV/AIDS. Policy makers are urged to intensify
      condom use campaigns.

PMID- 23136707
TI  - Some determinants of factors associated with HIV/AIDS risk behaviours among
      University of Dodoma students in Tanzania.
AB  - The paper examines whether variables of HIV/AIDS related knowledge, attitude and
      beliefs of Dodoma University students (UDOM) can predict practices which risk HIV
      infection. A pre-designed questionnaire was administered in a sample of 547 (539
      students and 8 staff members). Since variables involved were many and in many
      cases highly correlated and unobservable, data were analyzed using factor
      analysis. Multiple regression analysis were used to analyze factor scores
      obtained from factor analysis. Based on responses of students to practice
      questions, two factors emerged and were labeled as sex with high risk persons and
      common risk sexual behavior. The common predictors in the Multiple Linear
      Regression (MLR) for sex with high risk persons score (R2 = 5.1%, p < 0.001, F =
      4.873) and sex under the influence of alcohol (p < 0.001) respectively both had
      significant contribution from gender, knowledge on transmission through sexual
      contact, beliefs about HIV/AIDS and attitudes toward VCT testing. The MLR for
      common risk sexual behavior score (R2 = 5.4%, p < 0.001, F = 5.147) and sex
      without condom (p < 0.001) respectively both had significant contributions from
      gender and attitudes toward condom use. Knowledge on transmission through sexual
      contact, beliefs about HIV/AIDS and attitudes toward VCT testing and condom use
      appeared to be common determinants of HIV/AIDS risk behaviors among students.

PMID- 23136708
TI  - Advancement of scientific research on Helicobacter pylori in humans: where do we
      stand?
AB  - Helicobacter pylori (H. pylori) has been associated with humans for millions of
      years and its association wih gastroduodenal diseases has well been established.
      Research explosion has added vastly to the current dimensions. The new and
      unusual pattern of involvement in the form of diffuse duodenal nodular lymphoid
      hyperplasia (DDNLH) due to specific strain of H. pylorii has been reported from
      Kashmir recently, which heckles early recognition and treatment and on the other
      hand, we continue to face challenges so far as the prevention of carcinoma of
      stomach, a worst sequlae of H. pylori is concerned although population screening
      and prevention surveys are underway in many countries. Continued scientific work
      has now unfolded involvement of H.pylori in extragastric diseases like
      cerebrovascular, cardiovascular, idiopathic thrombocytopenia, sideroblastic
      anaemia, mental diseases, and collagen vascular disease .Moreover the beneficial
      effects of H. pylori with respect to allergic diseases and obesity are clear.
      Problem of drug resistance for eradication of H. pylori has arisen for which
      novel treatments are tried. Lactobacillus reuteri having ant H.pylori action is
      one of the promising treatment as is now available in India for usage. The main
      challenges which remain are prevention of H. pylori related diseases by effective
      treatment and screening procedures and development of a vaccine which can address
      all these issues including beneficial aspects of H. pylori.

PMID- 23136709
TI  - Prevalence of HIV-1 infection in Zanzibar: results from a national HIV-1
      serosurvey 2002.
AB  - OBJECTIVE: To determine the prevalence of HIV-1 infection in Pemba and Zanzibar
      islands METHODS: We used an interviewer-administered questionnaire that consisted
      of pre-coded and open-ended questions consisting of 29 items. The questionnaire
      was developed in English and translated into Swahili language before use. The
      questionnaire was pilot tested and modified before use. A total of 30 Shehias
      were randomly selected for the survey out of a total of 248 Shehias. A Shehia is
      the smallest government administrative unit in Pemba and Zanzibar that consists
      of two to three villages. The study sample was obtained through cluster random
      sampling of 76 households from each Shehia. Informed consent was sought from the
      Head of household and from each potential eligible participant. Eligibililty
      criteria included all persons aged 12 years and above who slept overnight in the
      selected household at the time of the study. Exclusion criteria included non
      residents of Zanzibar and Pemba such as tourists, Informed consent from persons
      below the age of 18 years were witnessed and ratified by their parents,
      guardians, caretakers or neighbours. All consenting participants were included in
      the study sample. Blood sports were collected using filters and tested for HIV-1
      using ELISA test at the Zanzibar Reference Laboratory. Samples found positive for
      ELISA were subjected to a 2nd ELISA test. RESULTS: The total number of persons
      who participated in the survey was 5852 out of 5868 eligible persons giving the
      overall response rate of 99.7%. Of the 5852 persons who participated in the
      survey, 41% (N = 2414) were males and 59% N = 3455) were females. The overall
      mean age of the study population was 30.4 years with age ranging from 12-65
      years. The overall prevalence of HIV-1 infection was 0.6% with more women being
      significantly affected than men (0.9% versus 0.2%; adjusted OR = 2.88, 95% CI =
      1.16-7.12). Of the 5852 persons who participated in the survey, 5.7% admitted
      having had casual partner in the past 6 months and of these 19.6% reported having
      used a condom during the most recent casual sex. CONCLUSION: We conclude that HIV
      1 infection in Zanzibar is still low and women are more affected than men.

PMID- 23136710
TI  - Influence of political culture on service provision in Kenyan rural health
      facilities.
AB  - OBJECTIVES: To explore the overall implications for an enhanced health system
      administrative capacity that not only takes account of global and regional
      developments, but that is also seen as legitimate domestically and is well
      equipped theoretically to deliver quality health care services in Kenyan rural
      health facilities. METHODS: The study used public hospitals as test cases. A
      field study was undertaken in western Kenya where four institutions were
      identified as research sites. In all the sites, a survey questionnaire was
      administered to both the community of health service providers as well as service
      users. RESULTS: The study found that health care service reforms must begin at a
      more fundamental level rather than just organizational development, human
      resource development and capacity building. CONCLUSIONS: The paper concludes by
      re-emphasizing the need to minimize the traditional tensions between the
      political and the public administration interface and the need to ensure that
      health care reforms are embedded or at least reflect the political choice and
      social structure of Kenyans in general.

PMID- 23136711
TI  - Undernutrition of orphans and vulnerable children: a comparison of cash transfer
      beneficiaries and non beneficiaries in Korogocho slums, Nairobi.
AB  - OBJECTIVE: To assess the prevalence and associated factors for undernutrition
      among the beneficiaries of Kenya Cash Transfer Program compared to non
      beneficiaries in Korogocho, Nairobi. Optimal nutrition reduces the prevalence of
      undernutrition and contributes to improved child survival and development.
      METHODS: A comparative descriptive cross-sectional study design in which a total
      of 336 children were sampled from the two groups each consisting 168 children. A
      questionnaire was administered to caregivers. A Food Frequency Questionnaire and
      a 24 Hour Recall sought information on foods consumed. Anthropometric
      measurements were taken based on standard procedures. Wasting, underweight and
      stunting were determined based on a z-score of > or = -2 or < -2 SD. A chi-square
      test was used to test significance associations of wasting, underweight and
      stunting with other variables. RESULTS: A majority (89.3%) and (73.8%) of the
      principal caregivers were females among the beneficiaries and non-beneficiaries
      respectively. Among the beneficiaries, prevalence of wasting was 6%, underweight
      6% and stunting 32.7%. Among non-beneficiaries, undernutrition was higher with
      wasting 9.5%, underweight 17.9% and stunting 37.5%. There was a significant
      difference (chi2 = 11.351, df = 1, p = 0.001) for underweight among the
      beneficiaries and non-beneficiaries. Nutrient inadequacies were high in vitamin
      A, folate and zinc in both beneficiaries and non-beneficiaries. In beneficiaries,
      undernutrition was significantly (p < 0.05) associated with number of children
      aged 6-59 months in the household, cash transfer used on food, carbohydrate
      intake, protein intake and frequency of breastfeeding. Among non-beneficiaries,
      undernutrition was significantly (p < 0.05) associated with number of household
      members, number of children 6-59 months in the household and income spent on
      food. CONCLUSIONS: There was improved nutritional status among the beneficiaries
      compared to non-beneficiaries. However, there is need of training beneficiaries
      on the best use of the cash transfers and educating them on consumption of
      adequate food to improve nutrient intake and eventually their nutritional status.

PMID- 23136712
TI  - Honokiol, a multifunctional tumor cell death inducer.
AB  - Honokiol is a small-molecule pharmacologically active component which has various
      medicinal applications. Increasing interest is paid on its multifunctional anti
      tumor effects including inducing tumor cell death, anti-angiogenesis, anti
      migration and anti-multiple drug resistance. We addressed a brief summary of the
      anti-tumor actions and potential applications of honokiol. This review is mainly
      focused on the multiple types of cell death induced by honokiol, and its
      potential role in overcoming multiple drug resistance.

PMID- 23136713
TI  - Magnetic nanoparticles for antimicrobial drug delivery.
AB  - Magnetic nanoparticles (MNP), fabricated by loading a therapeutic agent into a
      magnetic nanoparticle through encapsulation or adsorption, have gained particular
      interest during the last decade because of their intrinsic magnetic nature as
      well as enhanced physicochemical properties. Using their superior specifications
      MNPs can address the shortcomings of traditional therapeutic agents especially
      antimicrobials. The aim of this review, therefore, is to focus on the properties,
      fabrication and most recent finding in the application of MNPs for antimicrobial
      delivery.

PMID- 23136714
TI  - Simultaneous determination of seven major triterpenoids in Pyrola decorata H.
      Andres by LC-MS method.
AB  - A liquid chromatography-mass spectrometry method was developed and validated for
      the quantitative determination of seven triterpenoids, 3-beta-O-alpha-L
      arabinopyranosylsiaresinolic acid-28-O-beta-D-glucopyranosyl ester, ziyuglycoside
      I, pomolic acid, maslinic acid, colosic acid, oleanolic acid and ursolic acid in
      Pyrola decorata H. Andres. Chromatographic separation was achieved on a Hypersil
      C18 column using isocratic elution followed by a linear gradient elution of
      methanol and water as mobile phase. The analytes were ionized by atmospheric
      pressure chemical ionization source and determined on selected ion monitoring
      mode. All analytes showed good linearity (r2 > or = 0.9984) within the test
      ranges and the recovery rates were 94.5% - 103.3%. Satisfactory precision and
      reproducibility were obtained with relative standard deviation less than 5%. The
      method was simple, accurate and performed well in application to the
      determination of twenty commercial samples of P. decorata collected from
      different regions of China. It could be used for the quality control of both
      plant materials and preparations of P. decorata.

PMID- 23136715
TI  - A digitized impurity database analysis method for determining the impurity
      profiles of gatifloxacin in bulk materials and injections.
AB  - HPLC has become the most important analytical technique for impurity profiling in
      order to assure the quality of pharmaceutical products. Although HPLC is
      considered as a well-established technology, it requires CRS (chemical reference
      substances) of impurities for qualification and quantification of impurity peaks.
      Many impurity CRS have been widely used for the impurity profile control, which
      causes a high cost of production in practice. In this study, we developed a new
      method for impurity profiling control, so called digitized impurity database
      analysis, which does not directly use impurity CRS. Using a quinolone antibiotic,
      gatifloxacin as an example, we first analyzed its impurities by DAD (diode array
      detector) to compile a digitized impurity database and then used the database to
      analyze the impurities in the samples of domestic gatifloxacin bulk materials and
      injections in China. We identified the impurities in the chromatogram by
      combining two-dimensional chromatographic spectral correlation analyses of
      ultraviolet spectra data and relative retention times. The content of the
      impurities was determined using relative response factors of impurity to
      gatifloxacin as normalization factors. The digital impurity database analysis
      technology we developed is a "green", economic and convenient method that may
      eliminate the use of impurity CRS in the impurity profile control.

PMID- 23136716
TI  - Validated HPLC method for the simultaneous determination of taxol and ellagic
      acid in a Punica granatum fruit extract containing combination formulation.
AB  - A simple, rapid, precise and accurate isocratic reversed-phase high performance
      liquid chromatography (HPLC) method was developed and validated for the
      simultaneous determination of paclitaxel and ellagic acid in a combination
      nanoformulation. Separation was achieved using a 25 x 4.6 mm column, particle
      size 5 microm C18 reverse phase column (Luna), with a mobile phase consisting of
      methanol and 0.05% H3PO4, in gradient elution mode with a mobile phase flow rate
      of 1 mL/min, using UV visible detection at 230 nm. Sharp and well defined peaks
      were obtained at retention times of 13.75 min. and 11.6 min. for paclitaxel and
      ellagic acid, respectively. Regression analysis showed a good linear relationship
      (r2 = 0.996 +/- 0.0011) and (r2 = 0.993 +/- 0.0011) over wide ranges of 5-500
      microg/ml and 1-500 microg/ml for paclitaxel and ellagic acid, respectively. LOD
      and LOQ of paclitaxel were 30 ng/ml and 100 ng/ml, respectively, while for
      ellagic acid LOD and LOQ were 300 ng/ml and 1 microg/ml, respectively. The
      accuracy of the method was determined by recovery studies using the standard
      addition method and was found to be in the range of 99.61-101.21% and 98.70
      102.22% for paclitaxel and ellagic acid, respectively. The relative standard
      deviation (% RSD) for precision, repeatability and robustness was less than 2%.
      The ellagic acid content in fruits of Punica granatum and combination formulation
      with paclitaxel was analyzed and found to be 0.04% w/w and 0.0012%w/w,
      respectively. The proposed, developed and validated HPLC method for the
      simultaneous quantification of ellagic acid and paclitaxel can be used for the
      quality control and standardization of several crude drugs and different
      combination formulations, in which ellagic acid is present.

PMID- 23136717
TI  - Interactions between isoprenaline hydrochloride and bovine serum albumin (BSA) in
      capillary zone electrophoresis and affinity capillary electrophoresis.
AB  - Capillary zone electrophoresis (CZE) and affinity capillary electrophoresis (ACE)
      were developed to investigate the interactions between isoprenaline hydrochloride
      (IH) and bovine serum albumin (BSA). In CZE, the binding constant (Kb) was 4.07 x
      10(4) M(-1) (298 K) and 4.76 x 10(4) M(-1) (310K) using the Scatchard analysis.
      The number of binding sites (n) in this interaction was approximately one (n
      approximately equal 1). Furthermore, thermodynamic parameters, such as changes in
      Gibbs free energy (deltaG), enthalpy (deltaH), and entropy (deltaS) of the
      binding procedure were also obtained. At 298 K, deltaG, deltaH, and deltaS were 
      26.30 kJ x mol(-1), 10.02 kJ x mol(-1), and 0.12 kJ x mol(-) x K(-1),
      respectively. The deltaG at 310K was -27.76 kJ x mol(-1), whereas the deltaH and
      deltaS at 310 K were identical with that at 298 K. In ACE, a more reliable
      parameter, mobility ratio (M), was applied in the calculation of Kb. Kb (310K)
      obtained through this method was 9.80 x 10(4) and 9.24 x 10(4) M(-1) when IH and
      BSA were added to the buffer in varying concentrations, respectively. The
      obtained Kb may help in gaining some insights on the possible drug/protein
      interactions and in the early evaluation of the pharmacokinetic profile of the
      drug during cardiovascular drug screening.

PMID- 23136718
TI  - Preparation and characterization of gemcitabine liposome injections.
AB  - Gemcitabine liposome injection (stealth liposomes) has facilitated the targeting
      of gemcitabine for cancer treatment. We systemically review liposome-based drug
      delivery systems, which can improve pharmacokinetics, reduce side effects and
      potentially increase tumor uptake, for pancreatic cancer therapy. A novel
      liposomal formulation, which allows for higher tumor targeting efficiencies and
      can be used in current clinical trials to treat this challenging disease, has
      gained great popularity and attention. In this study, since extrusion technology
      was used to make sterile preparation of liposomes, the process included aseptic
      production process and sterile filtration. During the preparation, it has been
      found that the lipid concentration, emulsification speed and time, the
      homogenization times and pattern, the lipid solution temperature are all critical
      parameters for the character of the gemcitabine liposome injection. The particle
      size method and zeta potential method to characterize a PEGylated liposomal drug
      formulation of the anti-cancer agent gemcitabine was developed. The methods are
      specific, precise, reproducible and sensitive, therefore they are suitable for
      the determination of particle size and zeta potential of gemcitabine liposome
      injection. Negative staining technology of transmission electron microscopy
      revealed that gemcitabine liposome injection has a typical morphology, which
      enables liposomal surfaces could be seen so additional visual information on the
      stealth liposome can be routinely obtained in a fast and reliable manner.
      Moreover, the above three methods are simple, fast and would be used for
      continuous quality control of gemcitabine liposome injection when it moves to
      cGMP production scale.

PMID- 23136719
TI  - In situ and in vivo study of nasal absorption of borneol in rats.
AB  - The aim of this work was to study the in situ and in vivo nasal absorption of
      borneol. A novel single pass in situ nasal perfusion technique was applied to
      examine the rate and extent of nasal absorption of borneol by rats. Experimental
      conditions, such as perfusion rate, pH and drug concentration, were investigated.
      The in situ experiments showed that the nasal absorption of borneol was not
      dependent on drug concentration, and fitted a first order process. The absorption
      rate constant, Ka, influenced with an increase in perfusion speed. The borneol
      was well absorbed in the conditions of the nasal cavity within the pH range and
      pH value of physiological conditions. In vivo studies of borneol absorption were
      carried out in rats and the pharmacokinetics parameters of intranasal (i.n.) was
      compared with intravenous (i.v.) administration. The bioavailabilities of borneol
      was 90.82% for i.n. while Tmax values were 10min. MRT (Mean Residence Time) were
      262.55 +/- 67.35 min and 204.22 +/- 14.50 min for i.n. and i.v. methods,
      respectively. The results demonstrate that borneol could be absorbed promptly and
      thoroughly by i.n. administration in rats.

PMID- 23136720
TI  - Proniosomal formulation of curcumin having anti-inflammatory and anti-arthritic
      activity in different experimental animal models.
AB  - Curcumin, the active ingredient of the spice turmeric, has a long history as an
      herbal remedy for a variety of diseases. Transdermal drug delivery has been
      recognized as an alternative route to oral delivery. Proniosomes offer a
      versatile vesicle delivery concept with the potential for drug delivery via the
      transdermal route. In this study, different proniosomal gel bases were prepared
      by the ether injection method, using Span 60 and Span 80, Tween 20, cholesterol,
      and formulation PA2. They were characterized by scanning electron microscopy,
      revealing vesicular structures, and assessed for stability and effect on in vitro
      skin permeation using rat skin. Anti-inflammatory and anti-arthritic effects of
      formulation PA2 and PB1 were compared with a standard market product containing
      indomethacin. The effect of formulation PA2 and PB1 was evaluated for acute
      inflammation in carrageenan induced rat paw edema and for chronic inflammation in
      complete Freud's adjuvant (CFA) induced arthritis in rats. Further
      histopathological and radiographic evaluation was performed. The investigated
      curcumin loaded proniosomal formula proved to be non-irritant, non-toxic, but had
      lower anti-inflammatory and anti-arthritic effects than the marketed indomethacin
      products.

PMID- 23136721
TI  - Hypolipidemic effects of piperlonguminine in HepG2 cells and in Wistar rats.
AB  - A novel thermostable form of piperlonguminine (GB-N) was extracted from medicinal
      plant Piper longum in efforts to explore the bioactive components underlying the
      mechanism of Piper longum in reducing plasma lipids. In vitro, HepG2 cells were
      employed to investigate the effects of GB-N on regulating cellular total
      cholesterol and low-density lipoprotein (LDL) receptor (LDLR) mRNA abundance,
      while high-fat and high-cholesterol diet-induced hyperlipidemic Wistar rats were
      used to investigate in vivo effects of GB-N. Cellular total cholesterol assay
      showed that GB-N dose-dependently reduced cellular total cholesterol in HepG2
      cells in the presence and absence of elevated plasma cholesterol levels by 25%
      and 32%, respectively. Reverse transcription PCR assay showed that LDLR mRNA
      abundance was up-regulated dose-dependently by 142% via GB-N treatment in HepG2
      cells. Animal experiment revealed that GB-N dose-dependently reduced serum total
      cholesterol by 26%, triglyceride by 47%, LDL cholesterol by 30%, while increased
      serum high-density lipoprotein (HDL) cholesterol by 524% in diet-induced
      hyperlipidemic Wistar rats. In conclusion, the results suggest the potential
      therapeutic uses of GB-N in the prevention and treatment of hyperlipidemia and
      related diseases.

PMID- 23136722
TI  - Novel morphological features in the death of MCF-7 human breast cancer cells
      after exposure to anticancer drugs.
AB  - Cell death of human breast cancer cell line MCF-7/pDsRed2-Mito, caused by
      independent- or multi-administration of three anticancer drugs, cyclophosphamide
      [CPA], doxorubicin [DXR], and 5-fluorouracil [5-FU], was studied using
      fluorescence and electron microscopy. In our previous study using cell viability
      assays, microscopic inspection of heterochromatin condensation, a DNA
      fragmentation assay, and flow cytometric analyses, the death of MCF-7 cells was
      classified into two groups. The cell death induced by CPA or 5-FU was classified
      as apoptotic, while the cell death induced by DXR treatment or a mixture of all
      three anticancer drugs was classified as non-apoptotic. Here, we examined the
      morphology of the whole cell and its organelles, including the mitochondria,
      using electron microscopy. Mitochondria are of particular interest because they
      are the key organelle for the molecular apoptotic-death cascade. To monitor
      mitochondrial morphology, we used our previously constructed MCF-7/pDsRed2-Mito
      line, generated by introducing the pDsRed2-Mito vector into MCF-7 cells. The
      mitochondria in these cells emit red fluorescence. We found that the
      administration of DXR alone or of all three anticancer drugs together resulted in
      the clumping of the red-fluorescent materials on both sides of the round dying
      cells, interrupted by the nucleus. Detailed electron microscopic observation
      revealed that the novel morphology of the dying MCF-7 cells might be owing, not
      to destruction of the mitochondrial membrane, but to the tight structure of the
      nuclear membrane. Other anticancer drugs showed different, characteristic
      features in electron microscopic images, which suggested that death induced by
      anti-cancer drugs in the human breast cancer cell line, MCF-7, may result from
      any of a number of diverse processes.

PMID- 23136723
TI  - Phenolic glycosides as inhibitors of inducible nitric oxide synthase from Populus
      davidiana in LPS-activated RAW 264.7 murine macrophages.
AB  - Nitric oxide (NO) produced in large amounts by inducible nitric oxide synthase (i
      NOS) is known to be responsible for the vasodilation and hypotension observed in
      septic shock and inflammation. Inhibitors of i-NOS, thus, may be useful
      candidates for the treatment of inflammatory diseases that accompany the
      overproduction of NO. Two phenolic glycosides, salicortin (1) and salicortin-6'
      benzoate (2), were purified as active principles from the extracts of Populus
      davidiana by activity-guided purification procedures. They showed dose dependent
      inhibition of NO production in lipopolysaccharide (LPS)-activated RAW 264.7
      cells. The IC50 values of salicortin (1) and salicortin-6'-benzoate (2) was 15
      microM and over 50 microM, respectively. In immunoblot analysis, salicortin
      inhibited the expression of i-NOS. These new inhibitors of overproduction of NO
      may have potentials for the treatment of inflammation.

PMID- 23136724
TI  - The history of cholinesterase reactivation: hydroxylamine and pyridinium
      aldoximes.
AB  - Hydroxylamine (NH2OH) the substance which will turn out to be of importance to
      those interested in the treatment of organophosporus cholinesterase inhibitor
      exposure, was synthesized by Wilhem Clemens Lossen in 1865 while working in Halle
      as an assistant in the laboratory of Wilhelm Heinrich Heintz. The Lossen
      synthesis generated hydroxylamine in aqueous solution. Anhydrous hydroxylamine
      was prepared almost simultaneously by Lobry de Bruyn and Crismer (1891). Using
      hydroxylamine as a starting point Meyer synthesized aldoximes and ketoximes
      (1897). Lange, a PhD student of Ladenburg, isolated 2-methyl-pyridine (alpha
      picoline). Some fifty years later Wilson, working in the laboratory of
      Nachmansohn, demonstrated the ability of hydroxylamine to reactivate
      cholinesterase inhibited by organophosphates. Finally Wilson and Ginsburg using 2
      methyl-pyridine as a starting point synthesized the first pyridinium aldoxime
      reactivator of clinical relevance, pralidoxime (1955).

PMID- 23136725
TI  - [Botulinum neurotoxin--a therapy in migraine].
AB  - Although migraine is a common, paroxysmal, highly disabling disorder, the primary
      cause and the pathomechanism of migraine attacks are enigmatic. Experimental
      results suggest that activation of the trigeminovascular system is crucial in its
      pathogenesis. This activation leads to the release of vasoactive neuropeptides
      (calcitonin gene-related peptide - CGRP, and substance P - SP) and to neurogenic
      inflammation, and peripheral and central sensitisation are expressed. Botulinum
      neurotoxin-A (BoNT-A), a potent toxin produced by Clostridium botulinum, affects
      the nervous system through specific cleavage of the soluble NSF-attachment
      protein receptor complex (SNARE), like synaptosomal-associated protein of 25 kDa
      (SNAP-25). The result of this multistage process is blockade of the presynaptic
      release of pain neurotransmitters such as CGRP, SP and glutamate. A pooled
      analysis of the data from two programmes of Phase 3 Research Evaluating Migraine
      Prophylaxis Therapy (PREEMPT 1 and 2) with BoNT-A in chronic migraine
      demonstrated significant benefit of BoNT-A over placebo with regard to the
      numbers of headache days and migraine episodes. BoNT-A diminished the frequency
      of acute headache pain medication intake, and resulted in reductions in headache
      impact and improvements in scores on the Migraine-Specific Quality of Life
      Questionnaire. The treatments with BoNT-A proved safe and were well tolerated.

PMID- 23136726
TI  - [Fingolimod therapy in multiple sclerosis--the issue of the pathomechanism].
AB  - Multiple sclerosis is an autoimmune inflammatory disease of the central nervous
      system with neurodegenerative chararacteristics. The newly discovered per os
      administrable drug fingolimod (FTY720) has a different mechanism of action than
      the current disease-modifying therapies. In vivo the drug binds to four out of
      the five sphingosine-1-phosphate receptors after phosphorylation. Fingolimod
      phosphate (FTY720-P) causes internalization and degradation of the sphingosine-1
      phosphate receptors in the membrane of lymphocytes thus in contrast to
      sphingosine-1-phosphate it acts like a functional antagonist. In experimental
      autoimmune encephalomyelitis--an animal model of multiple sclerosis--fingolimod
      blocks the sphingosine-1-phosphate gradient controlled lymphocyte egress from the
      lymph nodes and therefore reduces the peripheral lymphocyte count especially the
      encephalitogenic Th17 subset is reduced. Modulation of the sinus lining and blood
      brain-barrier constructing endothelial cells also contributes to the complex
      mechanism of action. Additionally due to its liphohilic nature fingolimod is able
      to penetrate the blood brain barrier thus, beside its peripheral effects the drug
      can probably modulate the cells of the central nervous system directly.
      Presumably it can reduce neurodegeneration caused by astrogliosis through
      modification of astrocyte and oligodendrocyte activity. The results of current
      clinical studies show a bright perspective for both, the favourable therapeutic
      effects and the well-tolerated side effects.

PMID- 23136727
TI  - Stroke prevention--a population screening day in district XII of Budapest.
AB  - Along with advances in the treatment of acute stroke, new efforts have been made
      to enhance efficiency of the prevention of cerebrovascular diseases. Population
      screening is a way to contact high-risk patients, and there is an increasing
      international and national experience with the procedure. However, efforts are
      associated with high costs, so an efficient method, complying with local
      features, should be selected from the various methods. A stroke prevention day
      was organized in Szent Janos Hospital, localized in district XII, and data were
      analyzed. Taking advantage of the potentials of a large hospital, a comprehensive
      risk assessment - within the capacity of health care workers - was performed.
      Program and contact information of the screening day was published in the local
      newspaper of the district. Data of 48 residents of the district were analyzed. In
      addition to neurologists, a radiologist, a cardiologist and an ophtalmologist, as
      well as health care workers were involved in the project. A data sheet was filled
      in for all participants, including known risk factors, BMI, blood pressure and
      serum cholesterol levels. All participants had duplex sonography of the cervical
      vessels, cardiac evaluation and ophtalmic examination. Data were analyzed
      anonymously, and - if participants approved - postcode and educational level were
      also recorded. Among the 48 individuals screened, 35 were female and 13 were
      male. Average age was 62.86 (+/- 8.57) years, and participants were typically of
      higher educational level. 5 individuals had no known risk factors, most of them
      had 2-3 risk factors, and multiple risk factors were not uncommon. Individuals
      with six and seven risk factors were also found. 20 of 27 patients with known
      hypertension had target blood pressure levels. By duplex sonography, 36
      individuals had mild, 4 had significant atherosclerosis. There was no significant
      carotid stenosis or occlusion. Based on ophtalmic evaluation, 26 patients had
      signs of vascular disease (mainly hypertensive fundus changes). Cardiac
      evaluation detected 14 patients with cardiovascular risk. The high standard of
      primary care in the district was reflected by the fact that all the 6 high-risk
      individuals were already in the care of general practitioners (GP-s). One of the
      main conclusions from the evaluation of the data is that the press, family and
      local communities play a major role in recruiting people for a screening day. In
      order to increase efficiency and cost-effectiveness of the program, GP-s should
      also be involved in the planning process, because efficiency may be increased by
      pre-selecting high-risk individuals.

PMID- 23136728
TI  - [One year follow-up after stroke. A preliminary feasibility study in the
      Jozsefvaros district of Budapest].
AB  - Stroke is a major public health issue in Hungary with considerable regional
      differences in mortality. We have limited information to explain such regional
      differences. To assess these differences, we would need comparative followup
      studies optimally carried out by personal contact with the patient or the carer.
      According to several epidemiological studies, follow-up can be carried out with
      significantly lower cost and similar efficiency by telephone contact or regular
      mail. In this pilot study we intend to assess: 1. the efficacy of telephone
      follow-up one year after stroke in this geographical region 2. whether the
      efficacy of follow-up can be further increased with questionnaires sent out by
      regular mail 3. whether telephone and mail-based assessment is sufficient to
      perform a larger population based study. We included 135 patients hospitalized
      consecutively for acute cerebrovascular disease (stroke or TIA) by the Department
      of Neurology, Semmelweis University in January and February of 2008. Based on
      residence, patients were divided into three groups: those living in the least
      wealthy district of Budapest (i.e. District-8); those living in other districts
      of the city; and those living in suburban areas. One year after the hospital
      treatment follow-up was possible by telephone in 76%. Further 12 patients could
      be contacted by questionnaire sent out by regular mail. Efficacy of follow-up was
      altogether 84%. Even in this small group of patients, we have found a tendency
      for more severe strokes (p=0.06) and higher acute case fatality (32% vs. 5%,
      p=0.029) in residents of District-8 of Budapest compared to those residing in
      more wealthy districts of the city and in suburban areas. Survival rate one year
      after stroke or TIA was only 39% in those living in District-8, 66% in those
      living in other districts and 75% in suburban dwellers (p=0.006). Telephone and
      mail-based questionnaires are insufficient for follow-up in these regions even
      when applied in combination. These preliminary data raise the possibility that
      the socio-economical conditions might influence stroke severity and outcome in
      the population. A larger study to address this issue would require more accurate
      definition of patient-groups and more efficient follow-up methods.

PMID- 23136729
TI  - [One year follow-up after stroke. A preliminary feasibility study in the
      Jozsefvaros district of Budapest].

PMID- 23136730
TI  - [Study of the effects of vinpocetin on cognitive functions].
AB  - INTRODUCTION: Chronic cerebral hypoperfusion is a risk factor for the development
      of certain types of dementia. Mild cognitive impairment is a stage of predementia
      condition, because the symptoms are similar but not as severe as the symptoms in
      patients with dementia. Vinpocetine, due to its complex mechanism of action, has
      an important role in the improvement of chronic cerebral hypoperfusion.
      OBJECTIVES: The aim of our study was to determine the severity of the cognitive
      decline and to investigate the efficacy and safety of per os 18 months
      vinpocetine treatment in patients with mild cognitive impairment. METHODS: We
      used psychometrical tests (MMSE, ADAS-Cog) to assess the cognitive functions.
      CGIC-PGIC was used to evaluate the overall change in the disease status. ADL was
      used to assess the patient's daily activity and the Hamilton Depression Scale to
      evaluate the patient's mood. The assessments were performed at six visits during
      the 18 months treatment period. RESULTS: At the beginning of the treatment, the
      stage of our patients' mild cognitive impairment was moderately severe.
      Significant improvement was detected in the psychometrical tests after the 18
      months treatment period. The overall status of the disease improved significantly
      according both to the patient and the investigator. Also significant improvement
      was detected in daily activity. The complex improvement of the clinical symptoms
      affected the patients' mood positively. Moreover, vinpocetine was safe and had a
      good tolerability during the whole study period. CONCLUSIONS: Vinpocetine, due
      its complex mechanism of action, improved significantly the cognitive functions,
      overall disease status and quality of life in patients with chronic cerebral
      hypoperfusion. As a result, vinpocetine treatment can be recommended for patients
      with mild cognitive impairment.

PMID- 23136731
TI  - [The comparative analysis of arterial wall thickness and arterial wall stiffness
      in smoking and non-smoking university students].
AB  - AIM: Our aim was to detect the adverse effects of smoking on arterial wall
      thickness and arterial wall stiffness in young, healthy university students.
      QUESTION: Does only a few years of smoking result in measurable vascular
      alterations in healthy young people? METHODS: We measured the intima-media
      thickness (IMT) on both common carotids by means of carotid ultrasound, then we
      examined the stiffnessparameters of the blood vessels (pulse wave velocity, PWV;
      augmentation index, Aix) with the help of arteriograph. SUBJECTS: We recruited 25
      smoking and 25 non-smoking young volunteers aged 19-33 for our examinations.
      Exclusion citeria included any known diseases, abnormally high cholesterol
      levels, BMI value exceeding 30 kg/m2. Only regular smokers were allowed to
      participate in the smoking group (at least for six months, minimum five
      cigarettes a day). RESULTS: In case of smokers morphological, hemodinamic and
      stiffnessparameters showed significantly higher values compared to non-smokers.
      Mean bilateral IMT was 0.52 +/- 0.034 mm in case of smokers, while in non-smokers
      we measured 0.46 +/- 0.036 mm (this difference is significant: p<0.01). PWV and
      heart rate also showed significantly higher values in smoking group (PWV: p<0.01;
      heart rate: p<0.05). Unadjusted to age, gender and smoking status there was a
      significant correlation between IMT and PWV (0.1 mm thicker IMT - 0.6354 m/s
      faster PWV). Gender differences were found in vascular changes caused by smoking.
      CONCLUSION: The adverse effects of smoking on arterial wall thickness and
      arterial wall stiffness can be seen even at a young age, only after a few years
      of smoking. Both higher IMT and higher PWV sensitively predict vascular damages.

PMID- 23136732
TI  - [Neurological and psychiatrical aspects of urine incontinence].

PMID- 23136733
TI  - New non-invasive transcranial stimulation techniques in neuroplasticity research.

PMID- 23136734
TI  - [Ontogeny, systematics, and phylogenetics: space of future synthesis and a new
      model of the evolution of bilateria].
AB  - Ontogeny is considered as a process that allows combining two key components of
      biological systematics in an objective way: historically independent indicative
      attribution and phylogeny. It is proposed to designate the general theory that
      unifies the "statistical" traditional taxonomy and the dynamic evolutionary
      process on the basis ofontogenetic transformation of shapes of organisms as the
      ontogenetic systematics. One of the important practical applications is a new
      model of the evolution of bilaterally symmetric animals, which supposes an
      ancestral status of clonal asexual reproduction and its multiple reduction in a
      variety of Bilateria lines.

PMID- 23136735
TI  - [Morphogenetic changes during newt tail regeneration under changed gravity
      conditions].
AB  - Gravity-dependent shape alterations in newt tail regenerates are described, which
      were previously noticed in experiments onboard satellites Foton M2, M3 and in
      corresponding laboratory controls. Laboratory conditions were developed that
      allow reproducing this phenomenon persistently in the adult newts Pleurodeles
      waltl (Michahelles, 1830). The newts kept in an aquarium (in partial
      weightlessness) after 1/3 tail amputation developed normal lanceolate
      regenerates, while those that stayed on a moist mat (exposed to greater gravity
      than in aquarium) developed curved tail regenerates. Dynamics of the shape
      alterations were described using computer morphometric analysis. The curve was
      shown to develop at stage III of regeneration and to be caused by bending of the
      developing axial structures: the ependymal tube and the cartilage rode. Cellular
      processes were described that accompany the tail shape changes, such as cell
      migration and formation of dense aggregates. Unequal proliferation throughout the
      wound epidermis and blastema was revealed using BrdU assay. Proliferation
      increased within dorsal and apical regions of the regenerates in the newts kept
      on the mat cell compared with the aquarian animals.

PMID- 23136736
TI  - [Studies of prevalence rate of furunculosis caused by infection by Aeromonas
      salmonicida in salmonids of the southern part of Sakhalin Island].
AB  - Ichthyological studies of spawners of salmonids in the south of Sakhalin Island
      were studied. Cases of furunculosis disease were revealed. The agent of the
      disease Aeromonas salmonicida was isolated. Its morphological, physiological
      biochemical, and antagonistic properties were studied, and the virulence of the
      isolated strains was determined. For supporting the species status of the studied
      strains of A. salmonicida, a molecular-genetic analysis was performed.

PMID- 23136737
TI  - [Temperature as a factor of development of psychrotolerant mycelial bacteria
      complexes in soils of north regions].
AB  - It has been demonstrated that complexes of mycelial bacteria (actinomycetes), in
      which the amount of psychrotolerant actinomycetes reaches hundreds of thousands
      of CFU/g of the soil (frequently exceeding the portion of mesophilic forms), are
      developed in peat and podzolic soils of the tundra and taiga at low temperatures.
      As actinomycetes grow and develop in cold soils, their mycelium increases in
      length. Use of the molecular in situ hybridization method (fluorescent in situ
      hybridization, FISH) demonstrated that the portion of metabolically active
      mycelial actinobacteria exceeds the portion of unicellular actinobacteria in the
      Actinobacteria phylum. Specific peculiarities of psychrotolerant populations in
      relation to the spectrum of consumed substrates (histidine, mannitol, saccharose)
      were established by the method of multirespirometric testing.

PMID- 23136738
TI  - [Antijuvenile influence of the precocene on the development of adult antennae in
      the apple surface eating tortricid Archips podana Scop. (Lepidoptera:
      Tortricidae)].
AB  - The influence ofprecocene II, an antijuvenile agent, on the development of adult
      antennae in the apple surface eating tortricid A. podana Scop was demonstrated.
      Treatment of the fifth instar larvae and prepupae with different doses of
      precocene proved to cause different sensitivity of the specimens to the juvenile
      hormone deficit. Treatment with 450 and 600 microg precocene per specimen during
      the first days after ecdysis to the fifth instar caused the death of larvae.
      Treatment with 300, 450, and 600 microg per specimen on the third day of the
      fifth instar larvae and prepupae caused a delay in the development of adult
      antennae. The results are discussed with respect to the role of the juvenile
      hormone in the development of imaginal structures during metamorphosis.

PMID- 23136739
TI  - [Individual patterns of tonal (whistling) signals of bottlenose dolphins
      (Tursiops truncates) kept in relative isolation].
AB  - The results of study of the subaqueous acoustic signaling of bottlenose dolphins
      (Tursiopsis truncatus) in a dolphinarium are shown. Individual patterns of
      whistling signals of four individuals were described and analyzed. To determine
      which animal produced the sound, the method of "relative isolation" was used. It
      was found that the pattern included whistles specific for a particular individual
      ("signature whistles"). The percentage of these whistles in the patterns varied
      considerably among individuals. The signatures had variable frequency and
      duration. The phenomenon of "imitation" was typical for animals at higher
      positions in the hierarchy: generating "signatures" specific for other
      individuals. Besides the signatures, variable signals and whistles with simple
      frequency contours were found in the patterns.

PMID- 23136740
TI  - [Reduction of plant fibers in the digestive tract of the moose and the red deer].
AB  - A comparative study of the reduction of plant fibers moving in the digestive
      tract of nine red deer (Cervus elaphus) and six moose (Alces alces) was made. In
      the winter season, the character of fiber reduction in the moose and the red deer
      was similar. In the deer obtained in the early autumn, the relative concentration
      of small-sized fractions was significantly higher. A sharp decrease in the share
      oflarge-sized fibers was observed in the omasum as compared to the rumen and the
      reticulum. It was especially pronounced in the deer obtained in September.
      Deceleration of fibers of large-sized fractions in the rumen and the reticulum
      and the structure of the reticulo-omasal opening and its functions were
      considered.

PMID- 23136741
TI  - [Transgenerational effects of prenatal stress of different etiology].
AB  - This paper considers the transgenerational effects of prenatal stress of
      different etiology. The impacts of stress factors on the biochemical and
      morphofunctional parameters of life of the mother, fetus, and offspring in the
      first and subsequent generations (F1-F4) are estimated. Particular attention is
      paid to assessing changes in the parameters of physical development, the state of
      the hypothalamic-pituitary-adrenal axis, proinflammatory status, behavioral
      indicators, cognitive performance, and vegetative balance in the post-stress
      period. Contemporary concepts of possible mechanisms of transgenerational
      transmission of the effects of prenatal stress are considered.

PMID- 23136742
TI  - [Microbial communities and their ability to oxidize n-alkanes in the area of
      release of gas- and oil-containing fluids in Mid-Baikal (Cape Gorevoi Utes)].
AB  - The microbial community in the area of oil seep in Mid-Baikal (Cape Gorevoi Utes)
      was studied. The number of microorganisms that oxidize normal hydrocarbons,
      petroleum, and easily accessible organic matter in the water mass of the lake,
      bottom sediments, and bitumen structures was studied in 2005-2009. The high
      heterogeneity of the distribution of microorganisms associated with the
      deparaffination of oil in the areas of oil seeps was noted. The maximum
      concentrations of hydrocarbon-oxidizing microorganisms in the samples of bottom
      water above bitumen structures (up to 2200 +/- 175 CFU/ml) and in bitumen
      structures themselves (up to 170000 +/- 13000 CFU/g) were determined. A model
      experiment showed that in the conditions of low temperatures (4 degrees C) the
      degradation of the fraction of oil n-alkanes by the natural microbial community
      reaches 90% over a period of 60 days.

PMID- 23136743
TI  - [Ecology of the ringed seal (Pusa hispida) from the Bering Strait in the late
      Holocene].
AB  - The combined use of analysis of stable isotopes and archeozoological methods with
      respect to bony material from an ancient Eskimo settlement (dated 2370-810 years
      ago) made it possible to reveal the main distinguishing features of ringed seal
      in the past. On the basis of the data obtained, we suppose that in the late
      Holocene in the water area of the Bering Strait, there were seals of two
      different ecotopes: those reproducing on fast ice and those on pack ice differing
      not only in habitats, but also in the proportion of different food items in the
      diet. The ringed seals caught by ancient Eskimos during their life had a mixed
      diet consisting of crustaceans and fish, but in most individuals, a shift towards
      fish eating was observed. No significant changes in the feeding related to
      spawning were recorded. The dependence of feeding on body size was shown: bigger,
      mature individuals occupied higher trophic positions.

PMID- 23136744
TI  - [Morphofunctional analysis of testes and sperm in the assessment of male
      reproductive success in the bank vole (Clethrionomys glareolus)].
AB  - The morphofunctional analysis of testes and sperms in bank vole (Clethrionomys
      glareolus, Schreber, 1780) from a natural population is carried out to assess the
      reproductive potential of animals. It is shown that the reproductive success of
      males depends on the density of the population. Under physiological stress, such
      as a "peak" of the population size, the animals, against a background of
      accelerated aging, have activation of the hypothalamic-pituitary-adrenal axis,
      which contributes to oppression of the spermatogenesis process. The absolute
      weight of the testes is not always the determining factor in assessing the
      fertility of the animal. The informative indicators of the reproductive success
      of males and the population as a whole include the level of destructive changes
      in the endocrine and germinal regions of morphological defects of the testis and
      sperm.

PMID- 23136745
TI  - [Mycocin sensitivity patterns of the species Kluyveromyces: Kluyveromyces sensu
      lato vs. Kluyveromyces sensu stricto].
AB  - The Kluyveromyces species reassigned to the genera Lachancea and Vanderwaltozyma
      are insensitive to five mycocins secreted by Pichiamembranifaciens. The remaining
      Kluyveromyces species including species transferred to the genera Kazachstania,
      Nakaseomyces, and Tetrapisispora are sensitive to them. Only the neotype strain
      is insensitive to mycocins among Kluyveromyceslactis cultures.

PMID- 23136746
TI  - [The nature of changes of some immunophysiological characteristics in bream
      (Abramis brama) infected with plerocercoids (Ligula intestinalis) at various
      stages of parasite development].
AB  - The data from studies of the antimicrobial properties of blood serum, the content
      of total lipids, and antioxidant activity of immunocompetent tissues and organs
      of breams Abramis brama infected with plerocercoids Ligula intestinalis depending
      on the phase of development of the parasite are presented. The quantitative
      characteristics of the studied parameters are determined.

PMID- 23136747
TI  - [Morpho-ecological patterns and feeding of coho salmon Oncorhynchus kisutch fry
      in the period of downstream migration].
AB  - The principal characteristics of feeding of downstream-migrant and coastal young
      of the year of coho salmon are considered. The so-called potential downstream
      migrants and residents, which differ in size and feeding patterns, were
      distinguished among coastal fry. It is assumed that identification of particular
      coastal specimens to phenotypic groups of downstream migrants or nonmigrants of
      young of the year ofcoho salmon may be determined even in the daytime by such
      parameters as the body length, feeding intensity, and food spectrum.

PMID- 23136748
TI  - [Defensins in the honeybee antinfectious protection].
AB  - Specific conditions of the honeybee life honeybee life require the presence of
      effective mechanisms of antiinfectious protection whose one of the most important
      components are defensins--the family of antimicrobial peptides. In the honeybee,
      defensins are present in the form of two different peptides--defensin 1 and 2
      that are similar between each other only by 55.8 %. Defensin 1 synthesized in
      salivary glands plays an important role in social immunity, whereas defensin 2
      synthesized by cells of lat body and lymph is an important factor in the system
      of the honeybee individual immunity. Defensins are inducible, are controlled by
      interaction of Toll and Imd signal pathways and have a large specter of
      antimicrobial action.

PMID- 23136749
TI  - [Effect of light regime on biochemical parameters of development of stress
      reactions of Musca domestica L. lines with different lifspan].
AB  - The paper presents results obtained at recording under conditions of stresses of
      different character of activities of enzymes (tyrosinase, DOPA-oxidase,
      acetylcholinesterase) and level of the catecholamine content in tissues of head
      and fat body of imago and larvae of housefly from lines with different lifespan.
      A suggestion is put forward about different mechanisms mediating photoperiodic
      regulation of metabolism in individuals with different intensity of metabolism.

PMID- 23136750
TI  - [Comparative characteristics of the antioxidant glutathione complex in the Black
      Sea molluscs Mytilus galloprovincialis Lam. and Anadata inaequivalis Br].
AB  - Peculiarities of distribution of lipid peroxidation (LPO) products, glutathione
      (GSH) level, and antioxidant enzymes - glutathione peroxidase (GP) and
      glutathione reductase (GR) - in tissues of the Black Sea bivalve molluscs,
      Anadata inaequivalis Br. (anadara) and Mytilus galloprovincialis Lam. (mussel,
      black morph) were studied as well as their comparative characteristics were
      presented. There were established differences in organization of the glutathione
      organization and in the LPO intensity in tissues of these mollusc species. In all
      anadara tissues the intensity of LPO processes was lower than that in Mytilus
      galloprovincialis. The GP activity in hepatopancreas and gills in mussels was
      significantly higher than in anadara. On the contrary, in foot the GP activity
      and the GSH content in anadara exceeded essentially those in mussel. The revealed
      differences might reflect peculiarities of metabolism orientation in tissues of
      anadara and mussel as well as effect habitat conditions on them.

PMID- 23136751
TI  - [Perception by teenagers and adults of the changed by amplitude sound sequences
      used in models of movement of the sound source].
AB  - The ability to evaluate direction of amplitude changes of sound stimuli was
      studied in adults and in the 11-12- and 15-16-year old teenagers. The stimuli
      representing sequences of fragments of the tone of 1 kHz, whose amplitude is
      changing with time, are used as model of approach and withdrawal of the sound
      sources. The 11-12-year old teenagers at estimation of direction of amplitude
      changes were shown to make the significantly higher number of errors as compared
      with two other examined groups, including those in repeated experiments. The
      structure of errors - the ratio of the portion of errors at estimation of
      increasing and decreasing by amplitude stimulus - turned out to be different in
      teenagers and in adults. The question is discussed about the effect of unspecific
      activation of the large hemisphere cortex in teenagers on processes if taking
      solution about the complex sound stimulus, including a possibility estimation of
      approach and withdrawal of the sound source.

PMID- 23136752
TI  - [Role of acetylcholine in coordination od spontaneous electrical activity of
      various areas of the rat uterus].
AB  - Spontaneous electrical activity of myometrium was studied in areas of the uterine
      corpus, zone of its connection with uterine tube and cervix at intravenous
      administration of various acetylcholine concentrations. Under these conditions,
      changes of the frequency and amplitude characteristics of rhythmogenesis were
      studied both separately and in their combined active state. The presence of 10(
      3) M acetylcholine in the animal blood creates the most optimal conditions for
      synchronization and coordination of activities of all studied uterus areas.

PMID- 23136753
TI  - [Effect of antagonists of 5-HT receptors on modulation with serotonin of
      synaptical activity of projectional neurons of dorsolateral nucleus of rat
      amygdala].
AB  - The work deals with study of role of different serotonin (5-HT) receptor types in
      the process of synaptic activity modulation of rat dorsolateral amygdale
      projection neurons with serotonin. The selective antagonist of 5-HT1,2 receptors
      methylsergide maleate was shown to suppress the 5-HT inhibitory action on
      amplitude of the postsynaptic currents evoked by glutamate and GABA, whereas the
      antagonist of 5-HT3,4 receptors SDZ202-557 produced no effect on the above
      mentioned 5-HT action. The obtained action indicates that the 5-HT modulatory
      effect on the projectional neuron synaptic inputs is mediated by 5-HT receptors
      of the 1 and 2 types.

PMID- 23136754
TI  - [Hyperbaria and stress].
AB  - Causes of the appearance of stress-reaction at action of hyperbaira on the
      organism were studied on rats. It has been established that at the 5-h action of
      gas mixtures (oxygen-nitrogen and oxygen-argon) under pressure 0.35 and 0.5 MPa
      and partial pressure of oxygen 0.02-0.03 MPa in the chamber of the volume of 300
      1 there is obviously manifested stress confirmed by the corresponding markers.
      The appearance of stress was connected with the gas mixture density that amounts
      to 6 g/l, which interferes with respiration mechanically. Use of helium at the
      same pressure of the gas mixture did not cause stress, as its pressure did not
      exceed the normal air density. On the other hand, use for respiratory mixtures of
      elegas (SF6) with density of 6 g/l at the normal pressure produced obvious
      stress. No difference was revealed in action of nitrogen, argon or elegas at
      equal density. Thus, use of high pressures needs light gases (helium, hydrogen,
      neon) that have low density.

PMID- 23136755
TI  - [Effect of hypoxia in early perinatal ontogenesis on behavior and structural
      characteristics of the rat brain].
AB  - The study has shown the acute hypoxia in newborn rat pups to lead to disturbances
      of processes of formation of brain structures, behavior reactions, and learning
      in the subsequent ontogenesis. The single normobaric hypoxia at the 2nd day of
      life causes retardation of such integrative parameter or genera development and
      growth as body mass at the period of feeding. In such animals, essential
      disturbances of the sensorimotor development were revealed in forms of delay of
      reflex reactions of turning on a plane, negative geotaxis, and avoidance of edge.
      Also detected was action of hypoxia on hanging on a rope by using front legs (a
      symptom of muscle weakness). Morphological study has shown stereotypic reaction
      to the early postnatal action of hypoxia in all studies of all studied functional
      zones of neocortex - motor, sensomotor, auditory, visual. The death of nerve
      cells is predominant in the II-III associative layers, the sizes and number of
      pyramidal neurons are sharply decreased. Different hippocampus fields maturing in
      mammals show a characteristic response to hypoxia. In individual hippocampus
      fields there was detected different degree of death of neurons, predominant in
      the CA3 and CA4 fields. A possibility of modeling of perinatal encephalopathy
      with minimal brain dysfunctions in children is discussed.

PMID- 23136756
TI  - [Mass-transfer, utilization, and diffusion of oxygen in skeletal muscles of the
      stenohaline goby Gobius cobitus Pallas under conditions of hypoosmotic medium].
AB  - Effect of hypoosmotic conditions of medium on oxygen regime of skeletal muscles
      of the stenohalin goby Gobius cobitus Pallas was studied under conditions of
      experiment. The control fish group was maintained at 12-14 %o, the experimental
      one - at 4.8-5.6 per thousand. Duration of the experiment - 44-45 days, water
      temperature - 15 +/- 1 degrees C, photoperiod - 12 day/12 night. It was
      established that under conditions of external hypoosmia there occurred hydration
      of the goby skeletal muscles and a decrease of their diffusion capability with
      respect to oxygen. The latter was accompanied by the tissue P(O2) decrease, which
      is indicated by low values of P(O2) in the venous blood outflowing from muscles.
      For the first 14-16 days of adaptation to the hypoosmotic medium there were
      restricted processes of mass transfer and oxygen utilization, which was
      associated with a decrease of the voluminous tissue blood flow and the blood
      oxygen concentration. These changes occurred on the background of the blood
      plasma hydration and a decrease of the number of circulated erythrocytes, and
      then they were completely compensated.

PMID- 23136757
TI  - [Effect of retinol on interaction of the protein period1, oxytocin, and GABA at
      the prenatal period of formation of the circadian clock-mechanism in rats].
AB  - Clock-gene proteins are expressed in mammals in neurons of the hypothalamus
      suprachiasmatic nucleus and of other CNS structures, in muscles, viscercal
      organs, and vessels, and form circadian rhythms of many functions. Little is
      known about the factors of formation of the circadian mechanism at the prenatal
      period. In rats the E20 stage is characterized by a high level of oxytocin and
      selective expression of the first protein of the clock-genes PER1. The foal of
      the present study was to check the suggestion about the positive feedback between
      PER1 and oxytocin at the prenatal period as well as to elucidate a possible role
      of PER1 in regulation of interactions between oxytocin and GABA at the period of
      formation of the cerebral circadian mechanism of clock-genes. With aid of western
      blotting, we analyzed the nuclear and cytoplasmic fractions from anterior
      hypothalamus homogenate in pregnant females and embryos of rats (E20). The
      retinol metabolites through their nuclear receptor RORalpha are known to be bound
      to promoters of genes of oxytocin and per 1. Next day after administration of
      retinol to the females, a rise of PER1 content was noted in their cytoplasm,
      whereas in their embryos the PER1 content was elevated in the nucleus. In the
      embryo cytoplasm there was a significant rise of production of oxytocin receptors
      and a decrease of the level of enzymes of GABA synthesis (glutamate
      decarboxylases 67 and 65). The results indicate the oxytocin- and retinol
      dependent increase of the PER1 expression and the subsequent change of ratio of
      efficiency of oxytocin and GABA at the prenatal stage of formation of the
      circadian clock-mechanism of the rat embryo anterior hypothalamus.

PMID- 23136758
TI  - [Ultrastructural and morphological peculiarities of Turbellariae Bothrioplana
      semperi and the problem of monophilia of Seriata (Platyhelmimthes, Turbellaria)].
AB  - The ultrastructure and morphogenesis of rhabdites as well as the morphology of
      pharynx walls in Bothrioplana semperi (Turbellaria, Bothrioplanidae) are
      described. The ultrastructure of rhabdites and their morphogenesis in this
      species are close to those in Macrostomida (Turbellaria Archoophora). The order
      of muscle layers in the pharynx walls of Bothrioplana semperi makes it similar to
      Tricladida Maricola and some Tricladida Paludicola and Terricola. The analysis of
      ultrastructural and morphological characters in Bothrioplana semperi as compared
      to those in Turbellaria Proseriata and Tricladida is provided. It is shown that
      relation of apomorphic and plesiomorphic characters in the phyla analyzed
      corresponds the most to the viewpoint about the early divergence of these groups
      from early Turbellaria Neoophora. In this case Proseriata and Tricladida are not
      sister groups, while Bothrioplanidae should be regarded as a sister group to the
      ancestors of Tricladida and, possibly, Neodermata.

PMID- 23136759
TI  - [Peculiarities of distribution of cystathionine beta-synthase in the crustacean
      brain].
AB  - By using immunocytochemical method, distribution of cystathionine beta-synthase
      (CBS) was studied in the brain of 5 Crustacean species of the subclass of
      Malacostraca belonging to orders Stomatopoda and Decapoda that have different
      biologo-ecological characteristics. Both similar characteristics and differences
      in distribution of CBS-positive neurons were revealed in homologous brain parts.
      It is established that differences in the quantitative content of CBS
      immunoreactive neurons in the brain of the studied Crustaceans can be due not
      only to their systematic position, but also to peculiarities of their ecology.

PMID- 23136760
TI  - [Morphogenesis and reaction to hypoxia of atrial myoendocrine cells in chick
      embryos (Gallus gallus)].
AB  - The ultrastructural and stereomorphometrical study of the right atrium of chick
      embryos at the 14th day of incubation has shown the cardiomyocytes to divide by
      mitosis and to be at different stages of differentiation. In the cytoplasm of
      some muscle cells we detected secretory granules that by their sizes and
      morphology can be classified into the forming, mature, and dissolved forms. By
      the 18th day of incubation most cardiomyocytes are already differentiated, and
      the number of secretory granules in them rises. Under conditions of hypoxia,
      after 3 days, in myoendocrine cells there are noted signs of accelerated release
      of the peptides synthesized earlier and accumulated in granules, while after one
      week - of enhancement of their synthesis. It can be concluded that in chick
      embryos, beginning from at least the 14th incubation day, the system of
      natriuretic heart peptides takes part in regulation of hemodynamics and of water
      salt balance and responds to hypoxia.

PMID- 23136761
TI  - [Peculiarities of the structural-functional organization of motor neuropil of
      dragonfly thoracic ganglia].
AB  - The work considers the structural-functional relations existing in the motor
      neuropil of thoracic ganglia of dragonflies - the animals able to perform very
      complex and fast maneuvers in the flight. The motor neuropil in dragonflies is
      shown to be more differentiated than in the lees mobile insects, while motor
      nuclei in neuropil are more clearly outlined and closer to each other. There are
      revealed dendrites of motoneurons of pedal muscles (the middle nucleus), which
      are running into the anterior and posterior nuclei that contain dendrites of
      motoneurons of wing muscles. A possible role of such approaching is discussed for
      close functional interaction of wing and foot muscles, which is necessary to
      dragonflies during flight at their catching of large insects with aid of legs.
      Peculiarities are considered in structural organization of motoneurons of wing
      muscles dragonflies and locusts, which indicate the greater functional
      possibilities peculiar to motoneurons of the dragonflies motor apparatus.

PMID- 23136762
TI  - [Olfaction of dragonflies Aeschna grandis].

PMID- 23136763
TI  - [Cells in the system of multicelular organisms from positions of non-linear
      dynamics].
AB  - The organism physiological systems forming a hierarchic network with mutual
      dependence and subordination can be considered as systems with non-linear
      dynamics including positive and negative feedbacks. In the course of evolution
      there occurred selection of robust, flexible, modular systems capable for
      adaptive self-organization by non-linear interaction of components, which leads
      to formation of the ordered in space and time robust and plastic organization of
      the whole. Cells of multicellular organisms are capable for coordinated "social"
      behavior with formation of ordered cell assemblies, which provides a possibility
      of morphological and functional variability correlating with manifestations of
      the large spectrum of adaptive reactions. The multicellular organism is the
      multilevel system with hierarchy of numerous subsystems capable for adaptive self
      organization; disturbance of their homeostasis can lead to pathological changes.
      The healthy organism regulates homeostasis, self-renewal, differentiation, and
      apoptosis of cells serving its parts and construction blocks by preserving its
      integrity and controlling behavior of cells. The systemic approach taking into
      account biological regularities of the appearance and development of functions in
      evolution of multicellular organisms opens new possibilities for diagnostics and
      treatment of many diseases.

PMID- 23136764
TI  - [Photo-induced conformational motility of proteins].
AB  - The dynamics of proteins, detected by fluorescence, consists of three components:
      spontaneous dynamics, dipole-dipole photo-induced dynamics, thermal photo-induced
      dynamics. The photo-induced dynamics can lead to activation as well as
      inactivation of enzymes.

PMID- 23136765
TI  - [Study of cytotoxicity of fullerene C60 derivatives].
AB  - We investigated the cytotoxicity of the fullerene C60 derivatives. We showed that
      complexes of C60 fullerene with polyvinylpyrrolidone (m.w. of
      polyvinylpyrrolidone 10000 and 25000), C60-NO2-proline and C60-alanine had no
      toxic effect on HEp-2 cells. Sodium salt of polycarboxylic derivative of
      fullerene C60 exerted a pronounced toxic effect on this cell culture.

PMID- 23136766
TI  - [On functional amyloids of muscle proteins of titin family].
AB  - In this review basic characteristics of amyloidoses, conformational diseases of
      human and animals are given. Properties of amyloids formed by titin family
      proteins and their possible functional role are discussed by example of mammal
      hibernation.

PMID- 23136767
TI  - [Changes in titin and myosin heavy chain isoform composition in skeletal muscles
      of Mongolian gerbil (Meriones unguiculatus) after 12-day spaceflight].
AB  - Changes of titin and myosin heavy chain isoform composition in skeletal muscles
      (m. soleus, m. gastrocnemius, m. tibialis anterior, m. psoas major) in Mongolian
      Gerbil (Meriones unguiculatus ) were investigated after 12-day spaceflight on
      board of Russian space vehicle "Foton-M3". In m. psoas and m. soleus in the
      gerbils from "Flight" group the expected increase in the content of fast myosin
      heavy chain isoforms (IIxd and IIa, respectively) were observed. No significant
      differences were found in the content of IIxd and IIa isoforms of myosin heavy
      chain in m. tibialis anterior in the gerbils from control group as compared to
      that in "Flight" group. An unexpected increase in the content of slow myosin
      heavy chain I isoform and a decrease in the content of fast IIx/d isoform in m.
      gastrocnemius of the gerbils from "Flight" group were observed. In skeletal
      muscles of the gerbils from "Flight" group the relative content of titin N2A
      isoform was reduced (by 1,2-1,7 times), although the content of its NT-isoform,
      which was revealed in striated muscles of mammals in our experiments earlier,
      remained the same. When the content of titin N2A-isoform was decreased, no
      predictable abnormalities in sarcomeric structure and contractile ability of
      skeletal muscles in the gerbils from "Flight" group were found. An assumption on
      the leading role of titin NT-isoform in maintenance of structural and functional
      properties of striated muscles of mammals was made.

PMID- 23136768
TI  - [Suppression of vascular endothelium hyperpermeability by cell-permeating peptide
      inhibitors of myosin light chain kinase].
AB  - Novel peptides originating from the peptide inhibitor of myosin light chain
      kinase, L-PIK (Arg-Lys-Lys-Tyr-Lys-Tyr-Arg-Arg-Lys), have been studied for
      ability to attenuate the thrombin-induced hyperpermeability of endothelial cell
      monolayer in culture. Peptides [NalphaMeArg1]-Lys-Lys-Tyr-Lys-Tyr-Arg-(D)Arg8-Lys
      and H-Arg(NO2)Lys-Lys-Tyr-Lys-Tyr-Arg-Arg-Lys-NH2 (designated PIK2 and PIK4,
      respectively) appeared to be the most effective inhibitors of endothelial cell
      monolayer hyperpermebility, and surpassed other known peptide inhibitors of
      myosin light chain kinase derived from original L-PIK. Our results validate PIK2
      and PIK4 as the leading molecules for the development of novel drugs intended to
      counteract pathological hyperpermeability of vascular endothelium.

PMID- 23136769
TI  - [Regulatory function of the Na,K-ATPase alpha2 isoform].
AB  - A present review is devoted to the analysis of literature data and results of our
      own research in the field of the Na,K-ATPase molecular diversity. Abundant
      evidence shows that the Na,K-ATPase alpha2 isoform is not only involved in
      various specific cell functions but also affected by different regulatory factors
      as compared to the alpha1 isoform which carries the main pump function. Data
      gathered suggest that these features of alpha2 isoform are determined by its
      functional and molecular environment, localization in specific cellular
      microdomains and also by less stable integration into the cell membrane as
      compared to other isoforms of the Na,K-ATPase alpha subunit.

PMID- 23136770
TI  - [Study of the mechanisms of cytotoxic effect of uranyl nitrate].
AB  - The mechanisms of cytotoxic effect of uranyl nitrate were studied. It was shown
      that uranyl nitrate induced HEp-2 cell death, mainly by necrotic way. In the
      experiments in vitro, uranyl nitrate caused an appearance of 8-oxoguanine in DNA,
      indicating the induction of oxidative stress. The experiments with isolated rat
      liver mitochondria revealed that 1 mM uranyl nitrate decreased the respiration
      rates of mitochondria in state 3 and DNP-induced respiration. At the same time,
      uranyl nitrate had no influence on the opening of the mitochondrial permeability
      transition pore and decreased the rate of formation of H2O2 by mitochondria.
      Possible molecular mechanisms of uranyl-induced necrosis are discussed.

PMID- 23136771
TI  - [Dopamine as a possible substance for oncotherapy and for quantitative evaluation
      of cytosolic G-actin].
AB  - Viability, histology and ultrastructure of normal cells and cells of different
      degrees of malignancy after interaction with dopamine as well as the ability of
      these cells and isolated G-actin in model experiments to stain by Falck technique
      were studied. It is shown that dopamine, virtually having no effect on the
      viability of the "normal" non-tumorigenic transformed cells, noticeably reduces
      cell viability of slightly tumorigenic cells, causes a significant reduction in
      viability of attachable cancerous cells and a very significant decrease in cell
      viability of cancerous cells growing in suspension. The intensity of fluorescence
      of the cytosole in cells treated with dopamine, has been very high and varied in
      different cultures, and that of isolated actin directly depended on its
      concentration. Common to all cell morphological feature of damage from the action
      of dopamine and the putative substrate of fluorescence was actodopamine filaments
      network strands (identified on the structure and size), which appears in the
      cytosole loci, where they were absent in control. The data show that dopamine can
      be used as an oncotherapeutic remedy and diagnostic tool interacting with G-actin
      as a cellular target.

PMID- 23136772
TI  - [Isolation and purification of human blood plasma proteins able to form potassium
      channels in artificial bilayer lipid membrane].
AB  - Protein fraction able to induce K(+)-selective transport across bilayer lipid
      membrane was isolated from human blood plasma with the use of the detergent and
      proteolytic enzyme-free method developed at our laboratory. After addition of the
      studied sample to the artificial membrane in the presence of 100 mM KCl, a
      discrete current change was observed. No channel activity was recorded in the
      presence of calcium and sodium ions. Channel forming activity of fraction was
      observed only in the presence of K+. Using a threefold gradient of KCl in the
      presence of studied proteins the potassium-selective potential balanced by
      voltage of -29 mV was registered. This value is very close to the theoretical
      Nernst potential in this case. This means that the examined ion channel is cation
      selective. According to data obtained with MS-MALDI-TOF/TOF and database NCBI
      three protein components were identified in isolated researched sample.

PMID- 23136773
TI  - [Oxidative power and intracellular distribution of mitochondria control cell
      oxygen regime when arterial hypoxemia occurs].
AB  - The regulatory impact of the mitochondria spatial distribution and enlargement in
      their oxidative power qO2 on the tissue oxygenation of skeletal muscle during
      hypoxia were studied. Investigations were performed by the mathematical modeling
      of 3D O2 diffusion-reaction in muscle fiber. The oxygen consumption rate VO2 and
      tissue pO2 were analyzed in response to a decrease in arterial blood oxygen
      concentration from 19.5 to 10 vol. % at a moderate load (3.5 ml/min per 100 g).
      The cells with evenly (case 1) and unevenly (case 2) distributed mitochondria
      were considered. According to calculations due to a rise in mitochondria
      oxidative power from 3.5 to 6.5 ml/min. per 100 g of tissue it is possible to
      maintain muscle oxygen V(O2) at constant level of 3.5 ml/min per 100 g despite a
      decrease in O2 delivery. Minimum value of tissue pO2 was about 0 and an area of
      hypoxia appeared inside the cell in case 1. But hypoxia disappeared and minimum
      value of pO2 increased from 0 to 4 mm Hg if mitochondria were distributed
      unevenly (case 2). It is shown that the possibilities of such regulation were
      limited and depended on the ratio of "the degree of hypoxemia--the level of
      oxygen delivery." It was assumed that an increase in mitochondria enzyme activity
      and mitochondria migration to the places of the greatest oxygen consumption rate
      can improve oxygen regime in the cells in terms of their adaptation to hypoxia.
      It is possible that changes in mitochondrial oxidative power and their
      intracellular redistribution may be considered as a new dimension in regulation
      of cell oxygen regime.

PMID- 23136774
TI  - [The role of thiol antioxidants in restoring mitochondrial functions, modified by
      microbial metabolites].
AB  - The effects of phenolic acids of microbial origin on mitochondrial functions and
      the possibility of removing their effects by thiol antioxidants dithiotreitol and
      N-acethylcysteine were studied. The action of some phenolic acids on the redox
      state of NADH, the membrane potential and calcium capacity of mitochondria is due
      to their interaction with thiol groups. The partial restoration of mitochondrial
      functions occurred in the presence of dithiotreitol and N-acethylcysteine, the
      full recovery (short-term duration) was promoted by the combined action of
      dithiotreitol and menadione (vitamin K3). It was found that the protective effect
      of thiol antioxidants became prooxidant one, if the medium contained free iron
      and compounds with a quinone structure, capable of entering into a redox cycle
      with thiols. It is shown that the interaction of thiols with iron and menadione
      is accompanied by absorption of oxygen to form superoxide anion. Prooxidant
      effect of thiol antioxidants may explain the absence of the protective effect at
      the later stages of sepsis and systemic inflammatory syndrome.

PMID- 23136775
TI  - [Electrone probe microanalysis of rubidium retention in myocell of rat heart
      during acute ischemia].
AB  - In the given investigation contents of potassium and its physiological analog,
      rubidium, are determined in cardiomyocyte. Applying Electron Probe Microanalysis
      (EPMA), cytoplasmic concentrations of elements (K, Rb) are measured. The data
      obtained exhibit that for initial acute ischemia phase the active transport is
      involved in the uptake of rubidium which competes with potassium entry in cardiac
      myocell. Then, deep deenergization leads to the intracellular potassium depletion
      and rubidium retention. This suggests that Rb+ is physiologically not complete
      analog for K+. Results of combined perfusion with and without rubidium allow us
      to hypothesize the appearance of cascade of ionic transports to compensate acute
      ischemic disturbances following the oxygen and substrate deficiency.

PMID- 23136776
TI  - [Involvement of cyclic adenosine monophosphate in the control of motile behavior
      of Physarum polycephalum plasmodium].
AB  - Possible involvement of autocrine factors into the control of motile behavior via
      a receptor-mediated mechanism was investigated in Physarum polycephalum
      plasmodium, a multinuclear amoeboid cell with the auto-oscillatory mode of
      motility. Cyclic adenosine monophosphate (cAMP) and extracellular cAMP-specific
      phosphodiesterase, its involvement into the control of plasmodium motile behavior
      was proved by action of its strong inhibitor, were regarded as putative autocrine
      factors. It was shown that the plasmodium secreted cAMP. When it was introduced
      into agar support, 0,1-1 mM cAMP induced a delay of the plasmodium spreading and
      its transition to migration. When locally applied, cAMP at the same
      concentrations induced typical for attractant action the increase in oscillation
      frequency and the decrease of ectoplasm elasticity. The ability to exhibit
      positive chemotaxis in cAMP gradient and the dependence of its realization were
      shown to depend on the plasmodium state. Chemotaxis test specimens obtained from
      the migrating plasmodium, unlike those obtained from growing culture, generate
      alternative fronts which compete effectively with fronts oriented towards the
      attractant increment. The results obtained support our supposition stated earlier
      that advance of the Physarum polycephalum plasmodium leading edge is determined
      by local extracellular cAMP gradients arising from a time delay between secretion
      and hydrolysis of the nucleotide.

PMID- 23136777
TI  - [A simple kinetic model of contraction of striated muscle: full activation at
      full filament overlap in sarcomeres].
AB  - A simple kinetic model of muscle contraction is suggested. The rates of cross
      bridge transitions from one kinetic state to another are supposed to depend on
      the averaged (over ensemble of actin-bound bridges) strain. With a proper set of
      the strain-dependent rates the model fits well a broad set of experimental data.
      Due to its simplicity, the relation between strain and stress is described by a
      set of ordinary differential equations; the model can be used for simulation of
      complex 3D muscle contraction.

PMID- 23136778
TI  - [Novel approach to studying relationship of 3D structure and mechanical
      properties of biological tissue].
AB  - We present here a novel approach to studying the relationship of three
      dimensional structural organization of myocardial tissue as an example of
      biological tissue and its mechanical properties. The approach consists in the
      correlation of image series of the preparation internal structure obtained by
      confocal laser scanning microscope LSM-710 and the registration of tension
      deformation properties of the preparation. The spatial structure images of the
      segment of rat right ventricular wall at different stretching levels have been
      obtained. It is shown that the proposed approach provides the possibility to
      study the mechanisms of tension and strain development in living biological
      tissues in more detail.

PMID- 23136779
TI  - [Electromechanical coupling in cardiomyocytes from transmural layers of guinea
      pig left ventricle].
AB  - The electrical and mechanical activity of heart ventricle cardiomyocytes is known
      to vary depending on the spatial location of cells in the wall, in particular,
      transmurally from the sub-endocardial layer to the sub-epicardial one. To
      investigate intracellular mechanisms of the functional heterogeneity of
      cardiomyocytes we developed mathematical models of the electromechanical coupling
      in cardiomyocytes from different transmural layers across the left ventricle (LV)
      wall of guinea pig. It is shown that the mechanisms of both direct linkages and
      feedback in the electromechanical coupling contribute to differences in both the
      shape and duration of action potential, and speed characteristics of contraction
      between isolated cardiac myocytes from the sub-endocardial and sub-epicardial
      layers.

PMID- 23136780
TI  - [Electrocardiographic image of myocardial ischemia: real measurements and
      biophysical models. Part II].
AB  - By means of biophysical models of the heart electrical activity some alterations
      of the ST-T interval of an electrocardiogram were considered under changes of
      electrophysiological parameters of the cardiac muscle, characteristic for
      ischemia development. A computer program "The model of electrical activity of
      ischemic heart" developed in our Lab was used as a "Generator" for selection of
      model electrocardiosignals (ECS) when changing parameters of the transmembrane
      action potential (TAP) in "ischemic" area which was characterized in the model
      terms by its location and extent. The obvious development of ischemia was
      triggered by the deflection of TAP parameters from the reference values accepted
      for "conventional norm". For trapezoidal approximation of the TAP form chosen at
      the first stage of the work the following changed TAP parameters were used: (a)
      modification of duration of the horizontal plateau phase at the constant phase 3
      slope; (b) a change in the amplitude of the plateau phase at the constant
      duration of this phase and all TAP; (c) modification in the slope of the fast
      repolarization phase at the constant duration of the plateau phase (in this case,
      the total duration of TAP also changes); (d) reduction in the duration of phase 2
      at constant TAP duration, that, naturally, entails modification of the slope for
      the fast repolarization phase. We studied (out-of-scenarios developed before)
      separate effects of these parameters on changes of the T wave shape and the ST
      segment level. A number of new parameters for description of the changes observed
      in the ST-T interval pattern are offered and investigated. Computer experiments
      were performed using a system for 3D-modeling of the cardiac electrical activity.
      With the selected real and simulated ECSs a comparative study for diagnostic
      possibilities of some electrocardiographic criteria for detecting myocardial
      ischemia is carried out. The results obtained at this stage of work are of
      interest for identification and prediction of an electrophysiological state of
      the heart.

PMID- 23136781
TI  - [Computer simulations of microreentry in the SAN].
AB  - We have studied the dynamics of reentry inside the SAN. We have found that
      reentry is unstable at high intercellular conductance. Rotating reentry induces a
      slow migrating crescent-shaped functional block near the boundary of the SAN. An
      abnormal conduction from atrial tissue into the SAN occurs after decay of the
      reentry. ACh increases lifespan of the reentry in the SAN.

PMID- 23136782
TI  - [Myelination disorders in mechanism of hypogravity motor syndrome development].
AB  - When modeling effects of hypogravitation by the method of hindlimb unloading in
      rats the area of cross-section in lumbar part of a spinal cord was found to
      reduce. The analysis of spinal cord slides showed that these changes are
      associated with a decrease in the area of white substance of a spinal cord. Data
      obtained are consistent with our previous observation of a decrease in expression
      of the genes encoding myelin proteins. Results of our researches give the good
      reasons to believe that miyelinization failure in CNS is one of the factors that
      underlie the development of hypogravitational motor syndrome.

PMID- 23136783
TI  - [Changes of rat respiratory and locomotory muscles during aerobic exercise
      training in continuous and interval regimens].
AB  - Male Wistar rats were treadmill-trained for 8 weeks using one of the two
      regimens: with the constant running speed or with alternating high-speed and low
      speed intervals. Both training regimens led to an increase of rat aerobic
      capacities and to a higher citrate synthase activity in the medial head of
      gastrocnemius muscle. No differences between the effects of two training regimens
      were observed. However, in contrast to constant-speed training the interval one
      resulted in myocardium hypertrophy and also in less pronounced changes in
      diaphragm muscle, such as slow-direction shift of myosin phenotype and reduction
      of muscle fiber cross-sectional area. Neither of the training regimens had an
      effect on corticosterone and thyroid hormones levels in rat blood, whereas the
      interval training resulted in a higher level of testosterone. Anabolic influence
      of testosterone during interval aerobic training may be favorable for heart
      hemodynamic capacity and force characteristics of the diaphragm.

PMID- 23136784
TI  - [Motility of rats exposed to an altered photoperiod in the open field test].
AB  - Motility of rats exposed to an altered photoperiod has been studied in the open
      field test. It has been shown that physical activity of rats kept in darkness
      declined. The correlation parameters of locomotor activity as compared to
      previous data changed in animals kept in continuous light.

PMID- 23136785
TI  - [Method of receiving differential images of objects autofluorescence in the
      process of photobleaching].
AB  - The microscope with a high sensitive video camera and laser illumination was used
      to study autofluorescence changes of different structures in the photo bleached
      region with a different speed. The work with images using the ImageJ program is
      described in application how to receive differential images of objects
      autofluorescence in the process of photobleaching.

PMID- 23136786
TI  - [Device and programs for investigation of biological objects autofluorescence].
AB  - A method of fluorescent sub-diffractional microscopy is proposed based on using
      object dyeing by special dye, which is able to bind to some object structures and
      initially not absorb light, used for excitation of fluorescence. As a result of
      some processes small part of molecules is activated, that is converted to
      molecule able to absorb light and fluoresce sufficiently long to be registered by
      a sensitive video camera as separate spots covering tens of pixcels of camera
      matrix. Then registered molecules must be photobleached or transformed to
      nonfluorescing state by other influence and new portion of molecules is
      activated. This circle of "activation"--"fluorescence excitation and
      registration"--"photobleaching" may be repeated thousands times. The accuracy of
      center spots determination may be up to 2 nm. A collection of all calculated
      centers of spots in all registered frames may be used for reconstruction of
      object image with resolution not limited by diffraction. A method of improving
      visibility of spots produced by single molecules in object having
      autofluorescence is described.

PMID- 23136787
TI  - [Inversion of results upon using an "integral index" from an ostensibly
      authoritative source].
AB  - General results and conclusions of Nesterenko et al. [Biofizika 57(4)] have been
      distorted by uncritically applying an invalid "unifying formula" from a recent
      monograph [ISBN 978-5-02-035593-4]. Readers are asked to ignore the Russian
      publication but take the fully revised English version [Biophysics 57(4)] or
      contact the authors (tv-nesterenko@mail.ru, ubflab@ibp.ru). Here I briefly show
      the basic defects in the quasi-quantitative means of data analysis offered in
      that book, and mention some more problems regarding erroneous information in
      ostensibly authoritative sources.

PMID- 23136788
TI  - [Relation between fundamental and realized ecological niche].
AB  - Since species are formed in course of evolutionary process, their ecological
      niches are formed in the evolutionary process, too. Species exist in a state of
      evolutionary stasis diring hundreds of thousands and millions years. Stasis in
      sustained mainly by counterbalance of vectors of directional selection. Niche can
      be viewed as a multidimensional structure. Multitude of environmental factors
      acts upon every population, which cause elimination and, by that, selection for
      adaptation to each eliminating factor. Different directions of these vectors of
      selection lead to their counteractions; selection in one direction is interfered
      by selection in an opposite direction. The counterbalance of vectors of selection
      interferes with progressive evolution thus supporting stasis. During species
      existence in a stasis condition it endures a whole set of various deterioration
      of environment. Such deteriorations lead to imbalance of selective processes.
      Unbalanced vectors of selection form adaptations to extreme conditions of
      existence. Such adaptations are superfluous as for usual conditions; but they
      define fitness borders and, by that, borders of a fundamental niche. Realized
      niche, as well as fundamental one, is a multidimensional structure. Each
      population occupies a subniche of the specific realized niche. Thus, it occupies
      habitats where conditions are as close to an ecological optimum as can be
      admitted by the conditions in the given part of the areal. The sum of all
      subniches of populations--the specific realized niche--coincides with a part of
      fundamental niche because only the part of adaptive possibilities of a species
      sufficient for existence in the given environment is used. Interspecific
      competition, even when it is capable to restrict consumption of limiting
      resources, is not the reason of the realized niche limitation. Restriction of one
      or two of niche parameters does not influece all others parameters of its
      multidimensional space.

PMID- 23136789
TI  - [The biological substrate for the generation of behavioral acts].
AB  - There is a growing recognition that Central Pattern Generators (CPGs) play the
      fundamental role in the production of motor commands. A CPG is defined as a set
      of neurons involved in joint production of patterned sequenced output. It is
      generally believed that the sequence arises from the pattern of synaptic
      connections among these neurons. Alternatively, it was suggested (Sakharov, 1985)
      that the orderly organization of pattern-generating units might be due to the
      chemical diversity of their constituent neurons representing different
      phenotypes. Recent researches demonstrate that a given CPG can be reorganized to
      produce a different pattern of output activity. This multifunctionality can
      hardly be explained in terms of the anatomical (= synaptic) organization. The
      heterochemical approach appears to be more flexible. We hypothesize that dynamic
      fluctuations of the local extracellular milieu determine the physiological
      properties and receptor profile of individual neurons, and thus the self
      organisation of the latter into a CPG.

PMID- 23136790
TI  - [Specific immunity and polymorphism of breeding plumage in pied flycatcher
      (Ficedula hypoleuca) males (Aves: passeriformes)].
AB  - The relationship between the type of melanin-based plumage coloration and the
      strength of experimentally induced immune response was studied using as an
      example a pied flycatcher population from the Moscow Region. The plumage of pied
      flycatcher males exhibits the full spectrum of transitions from contrasting black
      and-white to cryptic brownish, the latter being very similar to the coloration of
      females. In spite of numerous studies, the nature of this polymorphism still
      remains vague. Unlike many other avian species with monocyclic breeding, a
      considerable fraction of pied flycatchers combines two energy-consuming
      productive processes, breeding and molt. During the main experimental treatment
      we activated the humoral immunity of free-living males in chick-rearing period by
      injection of nonpathogenic multigenic antigen (sheep red blood cells, SRBC) and
      estimated the strength of the immune responses after repeated captures in 6-8
      days. In addition, after each capture we estimated the numbers of leucocytes
      (WBC), heterophil to lymphocyte ratios (H/L) and measured night time basal
      metabolic rates (BMR). Non-molting males of different color types showed the same
      immune responses. Among molting birds, the strength of the immune response was
      significantly higher in pale males (morphs 4-7 by Drost's scale) than in bright
      males with rich melanin-based coloration (morphs 2-3). This difference resulted
      from two opposite processes. During molting, pale males heightened the antibody
      titer after immunization, while bright males tended to reduce the strength of
      immune response. Possibly such an asymmetry in immunocompetence at the first
      stage of molt reflects the different life strategies of pied flycatcher males -
      conspicuous birds less commonly combine breeding with molt than cryptic ones.

PMID- 23136791
TI  - [Speed of migratory movements in birds as adaptive behaviour].
AB  - Migration speed of 115 bird species from 35 families of 14 orders was analyzed.
      The data were collected from published sources based on ringing recoveries. It
      was found that average speed varies between 10 and 880 km/day, and the maximum
      speed varies between 30 and 1392 km/day, but in the majority of species the
      average speed values are in the range of 20-100, and the maximum speed values are
      in the range of 40-360 km/day There is significant positive correlation between
      the average and maximum speed. The ratio between maximum and average speed in
      different species varies significantly, and overall for all birds is 4:1. On
      average, shorebirds migrate twice as rapidly as passerines, and average speed of
      the raptors is rather higher than in shorebirds. The species from Turdidae family
      migrate significantly faster than the species from Fringillidae family, and the
      latter migrate faster than tits. No significant differences in migration speed
      were found between the species from Sylviidae and Turdidae families, as well as
      between Sylviidae and Motacillidae. Significant negative correlation was found
      between the body mass and average migration speed in the shorebirds, but no
      relationship between these parameters was found in the passerines. In many bird
      species, adult birds migrate significantly faster than juveniles, and in some
      species no difference in speed was found between males and females. In the
      passerines, the average migration speed is significantly higher among long
      distance early-departing nocturnal migrants as compared with the short-distance
      late-departing diurnal ones. The spring migration speed was much higher than
      autumn speed, but in some species only. The beha-vior of migrants at flight and
      at stopovers is governed by a complex interaction between their species-specific
      foraging features, weather conditions, and habitat.

PMID- 23136792
TI  - [Giant protists (xenophyophores and komokiaceans) from the Clarion-Clipperton
      ferromanganese nodule field (Eastern Pacific)].
AB  - Our previous investigations showed that giant protists (xenophyophores and
      komokiaceans) are one of the key groups in the deep-sea mega- and macrobenthos,
      dominating in density and biomass in some areas of the World Ocean. Analyses of
      38600 seafloor photographs and fauna from 30 box-corers taken in the Russian
      Exploratory area at the Clarion-Clipperton Fracture Zone ferromanganese nodule
      field revealed a diverse and abundant fauna of these organisms. Xenophyophores
      were found on 70% of seafloor photographs. Their abundance averaged 1600
      specimens per hectare, whereas abundance of the next common group, Actiniaria,
      did not exceed 170 specimens per hectare. The maximum abundance of xenophyophores
      was 12 specimens per m2 (equal to 120000 specimens per hectare). In the box
      corers, xenophyophores were found in 30% of samples. The most common group in
      these samples was Komokiacea. They occurred in 100% of samples. It was shown
      earlier that abundance and species diversity of macro- and meiobenthos increased
      when xenophyophores and komokiaceans were present. On the Russian exploratory
      area, the giant protists structure benthic communities. Study of these protists
      is especially important in the light of mining planned in the deep sea and for
      understanding of recovery of benthic communities after mining. We have found 6
      species of xenophyophores, 4 of them were new and 25 species of komokiaceans,
      most part of part of them was not known earlier.

PMID- 23136793
TI  - [Demonstration of the remote effect of baculovirus vertical transmission, with
      gypsy moth Lymantria dispar L. (Lepidoptera, Lymantriidae) as an example].
AB  - It is demonstrated for the first time that viral infection can be formed in
      insects survived after infection of gypsy moth larvae by nucleopolyhedrovirus
      (NPV), and cause subsequent mortality of individuals during, at minimum, two
      generations (the period of observations). The vertical virus transmission is
      carried by both male and female insects survived after infection. It is shown by
      means of PCR that the level of virus carrying in gypsy moth embryos of
      generations F1 and F2 is higher than the number of insects killed by NPV.

PMID- 23136794
TI  - Age-related susceptibility and resistance to nonlethal Plasmodium yoelii
      infection in C57BL/6 mice.
AB  - In cases of human malaria, children suffer very high rates of morbidity and
      mortality. To analyse the mechanisms involved in age-dependent protection against
      malaria, we investigated the characterization of immune responses to Plasmodium
      yoelii 17XNL (P.y 17XNL) in young (3 weeks) and middle-aged (8 months) C57BL/6
      mice. In this study, we found that 100% of young mice succumbed to P.y 17XNL
      infection with higher parasitemia, while middle-aged mice were able to clear
      blood parasites and no mortality was observed. These observations suggested that
      the young C57BL/6 mice were susceptible to P.y 17XNL infection, whereas the
      middle-aged mice were resistant. Cellular analysis revealed that both the numbers
      of splenic myeloid dendritic cells (mDCs) as well as the expression of DC
      maturation markers were higher in middle-aged mice than those in young mice. The
      numbers of IgG1- or IgG2a-secreting B cells increased markedly in middle-aged
      mice after infection with P.y 17XNL. The dynamic change of the number of
      CD4+CD25+Foxp3+ regulatory T cells (Tregs) in mice infected with P.y 17XNL was
      also different between the two groups. In addition, the levels of IFN-gamma and
      NO increased in both groups during early parasite infection, while there was also
      an obvious increase in IL-4 production in the infected middle-aged mice. The
      change in IL-10 levels following infection was consistent with that of the change
      in the number of Tregs. The survival of middle-aged mice following P.y 17XNL
      infection was dependent upon the establishment of effective Thl and Th2 responses
      and a successful switch between Th1 and Th2 responses, as well as appropriate
      functioning of Tregs.

PMID- 23136795
TI  - Pomphorhynchidae and quadrigyridae (Acanthocephala), including a new genus and
      species (Pallisentinae), from freshwater fishes, Cobitidae and Cyprinodontidae,
      in Turkey.
AB  - During a survey of freshwater fishes from Turkey two species of Acanthocephala,
      one of them new, were found. Pomphorhynchus tereticollis (Pomphorhynchidae) is
      reported at 24% prevalence in 37 Cobitis bilseli (Cobitidae) from Lake Beysehir,
      Konya, for the first time. The eoacanthoacaphalan Triaspiron aphanii gen. n. et
      sp. n. (Quadrigyridae), at a prevalence of 90%, is described from 29 Aphanius
      mento (Cyprinodontidae), from Kirkgoz Springs, Antalya. The new genus most
      closely resembles Raosentis Datta, 1947, both having a small spindle shaped
      trunk, and Acanthogyrus Thapar, 1927, both having a proboscis armature of three
      circles of hooks. Triaspiron differs from Raosentis in proboscis shape,
      cylindrical not globular, proboscis armature, three circles, a total of 16 hooks
      in all, not four circles, a total of 26-30 hooks in all, and trunk spination, two
      fields of spines in the anterior field with spines arranged in up to 40 circular
      rows, not a single field with 9-17 rows of spines. Triaspiron differs from
      Acanthogyrus in having fewer proboscis hooks, 16 compared with 18-24, arranged in
      three circles, one anterior and two posteriorly placed, with an unarmed region
      between, not three circles of hooks evenly spaced, and two fields of trunk
      spines, not one.

PMID- 23136796
TI  - Four additional hepatozoon species (Apicomplexa: Hepatozoidae) from north Florida
      ratsnakes, genus Pantherophis.
AB  - Records from a colubrid host are reported for Hepatozoon horridus, described
      originally from a viperid snake. Hepatozoon horridus in Pantherophis guttatus
      (Colubridae) has gamonts 14-18.0 by 4.0-5.5 microm, with length by width (LW) 60
      99 microm2, and L/W ratio 2.5-3.9. Spherical to elongate, usually ovoid oocysts
      with L/W ratio 1.0-3.7 contain 16-160 spherical to usually ovoid sporocysts 15-31
      by 14-26 microm, with L/W ratio 1.0-1.4, that contain 5-24 sporozoites. Two
      additional Hepatozoon species are described from ratsnakes in north Florida.
      Hepatozoon quadrivittata n. sp. from Pantherophis obsoletus quadrivittatus has
      gamonts 12-17 by 4-6 microm, LW 56-102 microm2, and L/W ratio 2.6-3.8. Nearly
      spherical oocysts with L/W 1.0-1.1 contain 5-227 spherical to slightly ovoid
      sporocysts 20-48 by 19-45 microm, with L/W ratio 1.0-1.4, that contain 13-48
      sporozoites. Hepatozoon spiloides n. sp. from Pantherophis obsoletus spiloides
      forms gamonts 12-15 by 4-5 microm with LW 48-75 microm2 and L/W ratio 2.6-3.5.
      Occasionally rounded but usually elongate oocysts, with L/W ratio 1.0-2.7,
      contain 5-21 spherical to elongate sporocysts 28-43 by 18-35 microm, L/W ratio
      2.5-3.9. In the distinctive Hepatozoon sp. present in Pantherophis obsoletus
      spiloides, gamonts are 13-17 by 5-10 microm, with LW 75-140 microm2 and L/W ratio
      1.4-3.0. Infected erythrocytes are always distorted and enlarged on average 2.5
      times the size of uninfected cells, with nuclei enlarged by one-third and broadly
      elongated. Gamonts often stained deep blue, and cytoplasm of erythrocytes
      infected with mature gamonts was always dehemoglobinized. Sporogony could not be
      obtained in three feedings by hundreds of Aedes aegypti, which usually died
      within the first 24-48 hr.

PMID- 23136797
TI  - Ultrastructure of the spermatozoon of the digenean Lecithocladium excisum
      (Rudolphi, 1819) (Hemiuroidea: Hemiuridae), a parasite of marine teleosts in
      Senegal.
AB  - The present study describes the ultrastructure of the mature spermatozoon of
      Lecithocladium excisum (Rudolphi, 1819) (Digenea: Hemiuroidea: Hemiuridae) from
      the stomach of the marine teleost Scomber japonicus Houttuyn (Scombridae)
      captured in the Atlantic Ocean, off Dakar (Senegal). The ultrastructural
      organization of the spermatozoon of L. excisum follows the general model
      described in most digeneans. It presents two axonemes of the 9+'1' pattern of the
      Trepaxonemata, nucleus, mitochondrion and parallel cortical microtubules, among
      other characters. However, some particularities of the spermatozoon of L. excisum
      are (i) the presence of a membranous ornamentation not associated with cortical
      microtubules in its anterior extremity, (ii) the presence of a very reduced
      number of cortical microtubules located only in the ventral side of the
      spermatozoon and (iii) the absence of several structures described in most
      digeneans such as spine-like bodies and cytoplasmic expansions.

PMID- 23136798
TI  - Spermiogenesis and spermatozoon ultrastructure of Hunterella nodulosa (Cestoda:
      Caryophyllidea), a monozoic parasite of suckers (Catostomidae) in North America.
AB  - Spermiogenesis and ultrastructure of mature spermatozoon of the caryophyllidean
      cestode Hunterella nodulosa, a parasite of suckers (Catostomidae), have been
      studied by transmission electron microscopy. This monozoic tapeworm is unique in
      its mode of attachment and represents the second North American species studied.
      The process of spermiogenesis of H. nodulosa follows the general pattern already
      described in other caryophyllideans. The most characteristic feature is the
      presence of a slight rotation of the flagellar bud, which seems to be a typical
      character of spermiogenesis in this cestode group. The mature spermatozoon of H.
      nodulosa is characterized by the presence of one axoneme of 9 + "1" type of the
      trepaxonematan flatworms surrounded by a semi-arc of cortical microtubules in its
      anterior extremity, parallel nucleus and cortical microtubules arranged in a
      parallel pattern, which corresponds to the Type III pattern of cestode
      spermatozoa according to Levron et al. (2010). Comparison of the present data
      with those available for other caryophyllideans did not reveal substantial
      differences, even though they belong to different families, infect different
      hosts (catostomid, cyprinid and siluriform fishes) and occur in distant
      zoogeographical regions. This indicates uniformity of the process of sperm
      formation and spermatozoon ultrastructure in one of the evolutionarily most
      ancient groups of tapeworms.

PMID- 23136799
TI  - Crenosoma brasiliense sp. n. (Nematoda: Metastrongyloidea) parasitic in lesser
      grison, Galictis cuja (Molina, 1782) (Carnivora, Mustelidae) from Brazil, with a
      key to species of Crenosoma Molin, 1861.
AB  - This study describes Crenosoma brasiliense (Nematoda, Metastrongyloidea), a new
      species parasitic in bronchi and bronchioles of Galictis cuja (Molina)
      (Carnivora, Mustelidae) from Brazil. This species differs from other 11 species
      of Crenosoma by having a cuticular projection at the distal end of the spicules,
      forming a prominent blade at the tip of the spicule, a vulval cuticular appendage
      with a triangular shape and prominent vulval lips. There are no previous records
      of species of Metastrongyloidea in G. cuja or species of Crenosoma in South
      America. Therefore, the new species represents the first host record and first
      geographical record of species of Crenosoma in South America.

PMID- 23136800
TI  - New data on the morphology of some Far-Eastern species of Rhabdochona (Nematoda:
      Rhabdochonidae), as revealed by SEM observations.
AB  - Specimens of the nematode genus Rhabdochona Railliet, 1916 (Rhabdochonidae) were
      collected during helminthological examination of four species of cyprinid fishes
      in two rivers of the Amur River basin in the Russian Far East (Primorsky Region)
      in June 2011. Detailed light microscopical (LM) and scanning electron
      microscopical (SEM) examinations (the latter used for the first time for the
      reported nematode species) of the available material revealed the presence of
      three inadequately described nominal species of this genus: R. (Rhabdochona)
      denudata (Dujardin, 1845) from the spotted steed Hemibarbus maculatus Bleeker
      (Gobioninae), and R. (Rhabdochona) longispicula Belous in Roytman, 1963 and R.
      (Globochonoides) coronacauda Belous, 1965 from Culter alburnus Basilewsky
      (Cultrinae) in the Ilistaya River. Detailed morphological study of these worms,
      especially SEM examination, made it possible to reveal some previously unreported
      morphological features (e.g., the presence of sublabia or the character of
      ventral precloacal ridges) and to confirm other taxonomically important
      characters such as the shape of deirids, number of anterior prostomal teeth,
      number and situation of lateral preanal and postanal papillae or the detailed
      structure of the crown-like formation on the female tail tip in R. coronacauda.
      Unidentifiable Rhabdochona (Rhabdochona) gravid females were recorded from the
      humpback Chanodichthys dabryi (Bleeker) (Cultrinae) in the Ilistaya River and
      from the Amur minnow Rhynchocypris lagowskii (Dybowski) (Leuciscinae) in the
      Komissarovka River.

PMID- 23136801
TI  - Description of Rhabdochona (Globochona) rasborae sp. n. (Nematoda:
      Rhabdochonidae) from the freshwater cyprinid fish Rasbora paviana Tirant in
      southern Thailand.
AB  - A new nematode species, Rhabdochona (Globochona) rasborae sp. n.
      (Rhabdochonidae), is described from the intestine of the freshwater cyprinid fish
      (sidestripe rasbora) Rasbora paviana Tirant in the Bangbaimai Subdistrict, Muang
      District, Surat Thani Province, southern Thailand. It differs from other
      representatives of the subgenus Globochona Moravec, 1972 which possess eggs
      provided with lateral swellings in having a spinose formation at the tail tip of
      both sexes and in some other morphological features, such as the body length of
      gravid female (8.6-23.7 mm), presence of two-three swellings on the egg, eight
      anterior prostomal teeth, length ratio of spicules (1:5.3-6.7) and arrangement of
      male genital papillae. This is the third nominal species of Rhabdochona Railliet,
      1916 and the second species of the subgenus Globochona reported from fishes in
      Thailand. The three species of Rhabdochona recently described from fishes in
      Pakistan, viz. R. annai Kakar, Bilqees et Khan, 2012, R. bifurcatum [sic] Kakar
      et Bilqees, 2012, and R. pakistanica Kakar, Bilqees et Khan, 2012, are considered
      to be species inquirendae.

PMID- 23136802
TI  - A redescription of Pseudocharopinus pteromylaei Raibaut et Essafi, 1979
      (Siphonostomatoida: Lernaeopodidae) collected from the South African east coast.
AB  - Pseudocharopinus Kabata, 1964 is one of the 48 genera comprising the
      Lernaeopodidae (Copepoda, Siphonostomatoida). Currently there are 11 accepted
      species contained in Pseudocharopinus. Pseudocharopinus pteromylaei Raibaut et
      Essafi, 1979 infects the spiracles and gill filaments of Pteromylaeus bovinus
      (Geoffroy St. Hilaire) and is most similar in general appearance to P.
      pteroplateae (Yamaguti et Yamasu, 1959) from which it clearly differs in the size
      and dimensions of the dorsal shield and the posterior processes. Additional
      features of the antenna and the maxilliped ofP. pteromylaei, not previously
      illustrated, are discussed and illustrated while more detailed illustrations of
      other appendages are provided. This is the first report of the occurrence of a
      Pseudocharopinus species from the west Indian Ocean and the first report of P.
      pteromylaei off the east coast of South Africa.

PMID- 23136803
TI  - A new species of the rare endoparasitic copepod Entobius (Copepoda: Entobiidae)
      from Mexico with a key to the species of the genus.
AB  - Abstract: In a study of the benthic polychaete fauna of the southern Gulf of
      Mexico and the Caribbean Sea, several specimens of the terebellid polychaete
      Scionides reticulata (Ehlers) were found to host endoparasitic copepods that
      represent an undescribed species of the rare cyclopoid genus Entobius Dogiel,
      1948. The new species, E. scionides sp. n., can be distinguished from its
      congeners by a combination of characters including a genital region without
      constrictions, three-segmented antennules, a reduced antenna with a blunt
      terminal process, reduced ornamentation of endopods of legs 1-4 and its
      relatively small size (2.3-2.7 mm). It is the smallest species of the genus.
      Comments on immature females are also provided, but males of this species remain
      unknown. It has a high prevalence (53%) in populations of the terebellid S.
      reticulata in the southern Gulf of Mexico, but it is absent from the Caribbean.
      This is the first occurrence of this copepod genus in the Americas. The finding
      of the new species of Entobius in S. reticulata confirms the strict specificity
      of most members of the genus and expands the host range of this copepod genus. A
      key for the identification of the species of Entobius is provided.

PMID- 23136804
TI  - New genus and three new species of quill mites (Acari: Syringophilidae:
      Picobiinae) parasitising puffbirds (Aves: Piciformes).
AB  - Abstract: Three new species, belonging to the newly proposed genus Pseudopicobia
      gen. n., inhabiting body quill feathers of puff-birds (Piciformes: Bucconidae),
      are described: P nonnula sp. n. from Nonnula frontalis (Sclater) in Colombia, P
      malacoptila sp. n. from Malacoptila panamensis Lafresnaye in Colombia and P
      hapaloptila sp. n. from Hapaloptila castanea (Verreaux) in Ecuador. The new genus
      differs from morphologically similar genus Picobia Heller, 1878 by the absence of
      the genital setae, absence of the genital lobes, solenidia phiI represented by
      microsetae, and by the presence of setiform solenidia sigma I. Syringophilid
      mites are recorded from birds of this family for the first time.

PMID- 23136805
TI  - Multilocus genotyping of Giardia duodenalis isolates from red deer (Cervus
      elaphus) and roe deer (Capreolus capreolus) from Poland.
AB  - A total of 181 faecal samples were collected from wild cervids in two regions of
      Poland. Giardia cysts were detected in one faecal specimen from red deer and in
      two samples from roe deer. Fragments of the beta-giardin (bg) triose phosphate
      isomerase (tpi) and glutamate dehydrogenase (gdh) genes were successfully
      amplified from the Giardia isolate obtained from red deer, whereas only amplicons
      of bg and gdh were obtained from Giardia isolates derived from two roe deer. The
      result of genotyping and phylogenetic analysis showed that the G. duodenalis
      isolate from red deer belonged to sub-assemblage AIII, which has never been
      identified in humans, whereas isolates from roe deer clustered within zoonotic
      sub-assemblage AI. Further studies are necessary to explain which Giardia
      assemblages and/or sub-assemblages occur in wild cervids in various regions of
      the world. Moreover, the impact of Giardia infection on the health of wild
      cervids should also be elucidated.

PMID- 23136806
TI  - Effect of previous anesthesia experience on patients' knowledge and desire for
      information about anesthesia and the anesthesiologist: a 500 patients' survey
      from Greece.
AB  - BACKGROUND: This study aimed at assessing the effect of previous anesthesia
      experience on patients' knowledge of anesthesia and the role of
      anesthesiologists, on what they would want to know about anesthesia and the way
      they would like to be informed. METHODS: Questionnaires with fixed questions were
      distributed to consenting, consecutive surgical patients before the pre
      anesthetic visit. Patients were divided into two groups: patients with previous
      anesthesia experience (Group A) and patients without previous anesthesia
      experience (Group B). The questionnaires included patients' demographics,
      questions related to their knowledge about the anesthesiologists' role and about
      their desire for information. RESULTS: 500 questionnaires were analyzed. The
      majority of patients (94.2%) know that the anesthesiologist is a specialized
      doctor and 89.2% believe that the anesthesiologist watches over the patient
      throughout surgery. These results were similar in both groups. The majority of
      patients (98.2%) also want to meet the anesthesiologist before surgery and 78%
      want even more information. Only 65.6% want to be aware of all possible
      complications, in both groups, while 17.6% do not want to know anything about
      complications. In general, answers to specific questions regarding what the
      patients want to know about anesthesia did not differ between groups. The vast
      majority of patients wish to talk with the anesthesiologist before surgery.
      CONCLUSION: Previous anesthesia experience did not seem to influence patients'
      desire for meeting the anesthesiologist and seeking information. A strong desire
      to personally meet the anesthesiologist is expressed and patients' desire for
      even more information is noted.

PMID- 23136807
TI  - Reversal of rocuronium-induced neuromuscular block with sugammadex in heart
      failure patients: a prospective observational study.
AB  - The aim of this study was to assess the hemodynamic stability and efficacy of 2
      mg/kg sugammadex in reversing rocuronium-induced neuromuscular block in patients
      with heart failure. Twelve patients who had an ejection fraction < or = 25% and
      who were undergoing general anesthesia for cardiac resynchronization therapy, an
      automated implantable cardioverter-defibrillator, or battery replacement of the
      device were included. Neuromuscular function was monitored by acceleromyography
      of the adductor pollicis muscle. Each patient received 0.6 mg/kg of rocuronium
      and maintenance doses of 0.1 mg/kg when required. When the second twitch appeared
      at the end of surgery, the patients received 2 mg/kg sugammadex. After the
      administration of sugammadex, the time for recovery to a normalized train-of-four
      (TOF) ratio of 0.9 was 2.78 +/- 0.67 min. Blood pressure and heart rate remained
      stable up to 10 min after the administration of sugammadex and then increased by
      the 30-min assessment. Three patients had episodes of SpO2 < 90% in the
      postanesthesia care unit. No sugammadex-related adverse events were reported.
      Sugammadex can adequately restore neuromuscular function in heart failure
      patients under hemodynamically stable conditions. However, longer reversal times
      are required than previously observed in healthy, young patients.

PMID- 23136808
TI  - Inadvertent epidural injection of drugs for intravenous use. A review.
AB  - INTRODUCTION: The frequency of inadvertent injection of drugs in the epidural
      space is probably underestimated and underreported, but it can cause serious
      morbidity and possibly mortality. OBJECTIVE: The aim of this review is to collate
      reported incidents of this type, to describe the potential mechanisms of
      occurrence and to identify possible therapeutic solutions. METHODS: We searched
      into medical databases and reviewed reference lists of papers retrieved. RESULTS:
      A list is reported of more than 50 drugs that were inadvertently injected into
      the epidural space. This list includes drugs which produce no, little or short
      lasting neurological deficits, but also includes drugs that may be more etching
      and can result in temporary or even permanent neurological deficit. DISCUSSION:
      Most drugs do not lead to sequelae other than pain during injection or transient
      neurological complaints. Other drugs may have more deleterious consequences, such
      as paraplegia. Both the dose of the inadvertent injected drug and the time frame
      play an important role in the patient's outcome. "Syringe swap", "ampoule error",
      and epidural/intravenous line confusion due to inaccurate or absent colour coding
      of epidural catheters were the main sources of error. Preventive strategies,
      including non Luer-lock epidural injection ports, might increase safety.

PMID- 23136809
TI  - Sickle cell anaemia and the consequences on the anaesthetic management of cardiac
      surgery.
AB  - A review of the available literature on genetics and pathophysiology of Sickle
      Cell Anaemia was performed with special emphasis on the intraoperative management
      during cardiac surgery. Hypoxia, acidosis and hypothermia have been identified as
      independent sickling provoking factors. Although no official guidelines on
      transfusion for Sickle Cell patients have been published, useful directives on
      preoperative transfusion could be derived from available data. Additionally, we
      bundled and reviewed the published expertise in the management of cardiopulmonary
      bypass and the necessity of hypothermia during cardiac surgery in Sickle Cell
      patients. Our conclusion is that the available data in case reports and case
      series on cardiac surgery in case of Sickle Cell Anaemia suggest a necessary
      preoperative or on bypass blood transfusion to guarantee an uncomplicated course
      of cardiopulmonary bypass and hypothermia.

PMID- 23136810
TI  - Evidence-based medicine in anesthesiology.
AB  - Two decades ago, Evidence-Based Medicine (EBM) was introduced to improve the
      quality of medical care. Using EBM in practice can be seen as a cyclic process
      consisting of 5 steps. This paper explains how to apply these steps in
      anesthesiology. The EBM cycle involves: 1. Asking a relevant clinical question,
      2. Finding evidence to answer the question, 3. Appraising the evidence, 4.
      Applying the findings to practice, which means integrating evidence, clinical
      experience and patient preferences, and 5. Reviewing these steps. Applying EMB
      requires effort and certain skills, for example searching for evidence and
      appraising the quality of the evidence. Also important is a reflective attitude
      towards the practitioner's own practice. This paper aims at encouraging
      anesthesiologists to develop such skills and to implement the steps of EBM in
      their daily practice.

PMID- 23136811
TI  - Two cases of acquired methemoglobinemia.
AB  - Methemoglobinemia is a rare pathology that results from the oxidation of iron in
      the hemoglobin molecule. Oxidation of iron switches it from the ferrous to the
      ferric state, and impedes the ability of hemoglobin to carry oxygen. Hence,
      methemoglobinemia often results in hypoxemia. The disease can be hereditary or
      acquired, and its diagnosis can be challenging. This rare condition may often be
      missed by clinicians, since information on oxygen saturation provided by standard
      pulse oximeters is unreliable. We here present two cases of acquired
      methemoglobinemia. The first one is a 24-year old woman, who received dapsone as
      an alternative antibiotic therapy because of known allergies to a series of other
      antibiotics and who could not get weaned from mechanical ventilation despite
      minimal ventilator support. The second case describes a 49-year old man who
      developed respiratory insufficiency following the use of 'poppers' containing
      alkyl nitrites. Following treatment of both patients using the antidote methylene
      blue, they could be successfully weaned from mechanical ventilation.

PMID- 23136812
TI  - Modification of a dioxygen carrier, hemoCD, with PEGylated dendrons for extension
      of circulation time in the bloodstream.
AB  - A supramolecular diatomic receptor, hemoCD, was modified with PEGylated dendrons
      to extend its circulation time in the bloodstream. The core component was 4-oxo-4
      [[4-(10,15,20-tris(4-sulfonatophenyl)-21H,23H-porphin-5-yl)phenyl]amino]butanoic
      acid (Por-COOH). The building block of the dendrons was Fmoc-4-amino-4-(2
      carboxyethyl)heptanedioic acid (FmocTA), which was condensed with alpha-amino
      omega-methoxy-poly(ethylene glycol) (PEG(5000)-NH(2)) to yield an FmocG1-dendron.
      After deprotection, the G1-dendron was condensed with Por-COOH to yield G1-Por. A
      precursor (FmocNA) of an FmocG2-dendron was prepared via a condensation reaction
      of 4-amino-4-(2-t-butoxycarbonylethyl)heptanedioic acid di-t-butyl ester (TA-E)
      with FmocTA followed by hydrolysis of the resultant nona-carboxylic acid nona-t
      butyl ester. Condensation of FmocNA with PEG(5000)-NH(2) yielded an FmocG2
      dendron. After deprotection, the G2-dendron was condensed with Por-COOH to yield
      G2-Por. The ferrous complexes of G1- and G2-Pors formed stable 1:1 inclusion
      complexes with Py3CD, a per-O-methylated beta-cyclodextrin dimer with a pyridine
      linker, in aqueous solution yielding supramolecular complexes designated as G1
      hemoCD and G2-hemoCD, respectively. Both G1- and G2-hemoCDs bound molecular
      oxygen, with the O(2) affinities (P(1/2)) of hemoCD, G1-, and G2-hemoCDs at pH
      7.4 and 37  degrees C being 22, 20, and 20 Torr, respectively. The modification
      of hemoCD with the dendrons did not cause destabilization of the O(2) adducts via
      autoxidation, as indicated by their half-lives (t(1/2)) of 6.8, 6.1, and 5.5 h
      for hemoCD, G1-, and G2-hemoCDs, respectively. The blood concentration-time
      curves of G1- and G2-hemoCDs injected into the bloodstream of rats exhibited two
      phases, with the half-lives of the fast and slow decays being 0.45 and 5.3 h,
      respectively, for G1-hemoCD, and 0.20 and 12.8 h, respectively, for G2-hemoCD.
      The half-lives of hemoCD were 0.02 and 0.50 h, respectively. The circulation time
      of hemoCD was markedly extended by its modification with the PEGylated dendrons,
      which was very effective in protecting hemoCD against opsonization for uptake by
      the reticuloendothelial system.

PMID- 23136813
TI  - Endocytic pathway and resistance to cholesterol depletion of cholesterol derived
      cationic lipids for gene delivery.
AB  - Cholesterol-based cationic lipids have been widely used because of
      biocompatibility and serum resistance. However, the reason for the effectiveness
      of cholesterol-based cationic lipids remains unclear. We compared the
      transfection route of CHOL-E, a cholesterol-based cationic lipid having an amine
      head and an ether linker, with that of DOTAP. The luciferase assay with chemical
      inhibitors and microscopic observation of pathway markers revealed that clathrin
      mediated endocytosis is the main pathway for CHOL-E and DOTAP. However, CHOL-E
      showed resistance to cholesterol depletion by methyl-beta-cyclodextrin.
      Furthermore, CHOL-E recovered the transfection efficiency of DOTAP from
      cholesterol depletion. These results suggested that superior transfection of CHOL
      E might be partly derived from effects on the cell membrane. 

PMID- 23136814
TI  - Enzymatic characteristics of a recombinant neutral protease I (rNpI) from
      Aspergillus oryzae expressed in Pichia pastoris.
AB  - A truncated neutral protease I (NpI) from  Aspergillus oryzae  3.042 was
      expressed in  Pichia pastoris  with a high enzyme yield of 43101 U/mL. Its
      optimum pH was about 8.0, and it was stable in the pH range of 5.0-9.0. Its
      optimum temperature was about 55  degrees C and retained >90% activity at 50 
      degrees C for 120 min. Recombinant NpI (rNpI) was inhibited by Cu(2+) and EDTA.
      Eight cleavage sites of rNpI in oxidized insulin B-chain were determined by mass
      spectrometry, and five of them had high hydrophobic amino acid affinity, which
      makes it efficient in producing antihypertensive peptide IPP from beta-casein and
      a potential debittering agent. The high degree of hydrolysis (DH) of rNpI to
      soybean protein (8.8%) and peanut protein (11.1%) compared to papain and alcalase
      makes it a good candidate in the processing of oil industry byproducts. The
      mutagenesis of H(429), H(433), and E(453) in the deduced zinc-binding motif
      confirmed rNpI as a gluzincin. All of these results show the great potential of
      rNpI to be used in the protein hydrolysis industry.

PMID- 23136816
TI  - Kinetics study of reactions of alpha-pinene and beta-pinene with hydroxyl radical
      at 1-8 Torr and 240-340 K using the relative rate/discharge flow/mass
      spectrometry method.
AB  - The kinetics of reactions of alpha-pinene and beta-pinene with hydroxyl radicals
      (OH) has been investigated at 1-8 Torr and 240-340 K using the relative
      rate/discharge flow/mass spectrometry (RR/DF/MS) technique. Our kinetic results
      indicate that at 298 K the rate constant of the reactions of alpha-pinene and
      beta-pinene with hydroxyl radicals has little pressure dependence over the 1-8
      Torr pressure range, suggesting that the high pressure limit of these reactions
      has been reached at 1 Torr. The rate constant of these reactions was found to
      negatively depend on the temperature at 240-340 K, which is consistent with
      previous investigations using different techniques. The Arrhenius equation for
      alpha-pinene and beta-pinene with hydroxyl radical was determined to be k(alpha
      pinene) = (1.21 +/- 0.20) * 10(-11)exp[(441 +/- 46)/T] cm(3) molecule(-1) s(-1)
      and k(beta-pinene) = (1.65 +/- 0.10) * 10(-11)exp[(470 +/- 17)/T] cm(3) molecule(
      1) s(-1), respectively. Using the rate constant determined at 277 K in this work
      and the average global hydroxyl radical concentration, the atmospheric lifetime
      of alpha-pinene and beta-pinene was estimated to be 5.8 and 3.8 h, respectively.

PMID- 23136815
TI  - Autonomy in action: linking the act of looking to memory formation in infancy via
      dynamic neural fields.
AB  - Looking is a fundamental exploratory behavior by which infants acquire knowledge
      about the world. In theories of infant habituation, however, looking as an
      exploratory behavior has been deemphasized relative to the reliable nature with
      which looking indexes active cognitive processing. We present a new theory that
      connects looking to the dynamics of memory formation and formally implement this
      theory in a Dynamic Neural Field model that learns autonomously as it actively
      looks and looks away from a stimulus. We situate this model in a habituation task
      and illustrate the mechanisms by which looking, encoding, working memory
      formation, and long-term memory formation give rise to habituation across
      multiple stimulus and task contexts. We also illustrate how the act of looking
      and the temporal dynamics of learning affect each other. Finally, we test a new
      hypothesis about the sources of developmental differences in looking.

PMID- 23136817
TI  - A scientific evidence for the efficacy of biologic implants for soft tissue
      reconstruction.
AB  - The challenges and complications arising from abdominal surgery frequently
      necessitate soft tissue reconstruction or augmentation. Soft tissue repair
      generally has been revolutionised by the introduction of synthetic meshes, but
      their use is contra-indicated in contaminated or infected fields. Biologic
      materials derived from devitalised allo- or xenogeneic tissues have been proposed
      as a safer alternative to synthetics and provide an extracellular scaffold
      necessary for the in-growth of new blood vessels and infiltration of native
      stromal cells. We review the scientific evidence behind commercially available
      biologic prostheses in relation to the impact of tissue source, manufacturing
      processes and supplemental cross-linking on in vitro and in vivo (animal model
      and clinical) performance. Cross-linked meshes exhibit increased resistance to
      collagenase activity and degradation whilst still allowing tissue in-growth. Mesh
      durability may be the most important characteristic in determining optimal
      clinical outcomes, particularly in the context of the increased collagenase
      activity seen in contaminated or infected fields. Of all the biologic meshes
      currently available, HDMI cross-linked acellular porcine dermis has been
      associated with the best clinical outcomes in contaminated or infected fields.

PMID- 23136818
TI  - The role of biologic meshes in abdominal wall reconstruction.
AB  - There are unacceptably high rates of recurrence following surgery for incision
      hernia repair using suture repair techniques in isolation. As the reconstruction
      of abdominal walls has expanded with complex surgery, the materials used as
      adjuncts to support the repair have changed. In the article we review the current
      use of biologic meshes in abdominal wall reconstruction and the techniques used.

PMID- 23136819
TI  - Biologic meshes in perineal reconstruction following extra-levator
      abdominoperineal excision (elAPE).
AB  - Recent improvements in the outcome for low rectal cancer have focused on the
      reconstruction of the perineal defect following greater acceptance of the need
      for a wider perineal excision encompassing the levator ani complex. In this
      article we look at the use of biologic materials to close the perineal defect and
      compare this with the use of other techniques.

PMID- 23136820
TI  - The role of biologics in pelvic floor surgery.
AB  - The advent of laparoscopic surgery and with it Laparoscopic Ventral Mesh
      Rectopexy (LVMR) has revolutionised the management of internal/external rectal
      and vaginal vault prolapse. These procedures have traditionally been performed
      with synthetic meshes. Biologics have gained a prominent role over the last
      decade in LVMR as well as perineal procedures for rectocoele and cystocoele
      repair. We examine the existing literature on the use of biologics in pelvic
      floor surgery comparing this with literature on synthetic mesh for the key
      outcomes of infection rates, bowel/sexual function and recurrence.

PMID- 23136821
TI  - Collagen matrix injection combined with flap repair for complex anal fistula.
AB  - Several biomaterials have been proposed to treat anal fistula alone or in
      combination with other surgical procedures aiming to reduce recurrence rates
      while minimizing continence impairment. More recently a porcine dermal matrix
      injection has been proposed as infill biomaterial to treat fistulae. We propose
      an approach consisting of non-cutting seton positioning followed several weeks
      later by flap repair associated with dermal matrix injection into the fistula
      tracts. We report our experience with this two-staged procedure on 24 consecutive
      patients with complex anal fistulae with a median follow up of > 12 months. In
      our experience this two-stage approach seems to be safe and effective.

PMID- 23136822
TI  - Anal bulking agents for faecal incontinence.
AB  - The aim of this review was to assess and evaluate reports of studies on the
      efficacy of anal bulking agents used in the treatment of faecal incontinence. A
      systematic review of the literature was carried out to identify studies that have
      reported on the use of anal bulking agents. A variety of biomaterials have been
      employed for anal bulking. These include autologous fat, bovine glutaraldehyde
      cross-linked collagen, carbon-coated zirconium oxide beads, dextranomer
      microspheres in a gel, hydrogel cross-linked with polyacrylamide,
      polydimethylsiloxane elastomer in a gel, porcine dermal collagen and synthetic
      calcium hydroxylapatitie ceramic microspheres. Although the ideal site of
      injection (submucosal or intramuscular) and the mechanism of action remain the
      subject of debate, most published studies report a significant improvement in
      continence in at least 50% of subjects with mild to moderate symptoms with little
      or no associated morbidity.We concluded that anal bulking agents may be used to
      alleviate symptoms of faecal seepage and soilage.

PMID- 23136823
TI  - Biological materials in colorectal surgery: current applications and potential
      for the future.
AB  - Biological materials are increasingly used in abdominal surgery for ventral,
      pelvic and perineal reconstructions, especially in contaminated fields. Future
      applications are multi-fold and include prevention and one-step closure of
      infected areas. This includes prevention of abdominal, parastomal and pelvic
      hernia, but could also include prevention of separation of multiple anastomoses,
      suture- or staple-lines. Further indications could be a containment of infected
      and/or inflammatory areas and protection of vital implants such as vascular
      grafts. Reinforcement patches of high-risk anastomoses or unresectable
      perforation sites are possibilities at least. Current applications are based
      mostly on case series and better data is urgently needed. Clinical benefits need
      to be assessed in prospective studies to provide reliable proof of efficacy with
      a sufficient follow-up. Only superior results compared with standard treatment
      will justify the higher costs of these materials. To date, the use of biological
      materials is not standard and applications should be limited to case-by-case
      decision.

PMID- 23136824
TI  - Biologic meshes in colorectal surgery.

PMID- 23136825
TI  - Psychosocial predictors of sleep dysfunction: the role of anxiety sensitivity,
      dysfunctional beliefs, and neuroticism.
AB  - The present study examined the relationship of anxiety sensitivity, dysfunctional
      beliefs about sleep and neuroticism on sleep disturbance. Previous research of
      these three related concepts-each describing a different kind of reactivity to
      interoceptive or environmental events-have served as predictors of insomnia and
      insomnia-related distress; however, it is not known how these concepts have
      distinctive prediction of sleep outcomes. We completed an Internet survey of 149
      undergraduate student participants, a population with elevated risk for disturbed
      sleep. Participants completed a demographics questionnaire, the Anxiety
      Sensitivity Index (ASI), the Dysfunctional Beliefs and Attitudes about Sleep
      Scale (DBAS-16), the NEO Five-Factor Inventory, and the Pittsburgh Sleep Quality
      Index (PSQI). Results revealed a significant association between PSQI total score
      and the three variables of interest, ASI, DBAS, and neuroticism. However, in a
      stepwise regression, neuroticism was the statistically most important predictor
      of sleep disturbance. The DBAS was a statistically more important predictor than
      ASI total score; however, when the ASI was examined by subscale, DBAS was
      replaced in the model by the ASI Mental Incapacitation Concerns subscale. Our
      findings highlight the continued value of higher order concepts like neuroticism
      in the development of disorder-specific measures like the DBAS, as well as
      indicate that distress in response to cognitive symptoms (AS-mental
      incapacitation) may play a role in maintaining sleep dysfunction.

PMID- 23136826
TI  - Parameterization models for pesticide exposure via crop consumption.
AB  - An approach for estimating human exposure to pesticides via consumption of six
      important food crops is presented that can be used to extend multimedia models
      applied in health risk and life cycle impact assessment. We first assessed the
      variation of model output (pesticide residues per kg applied) as a function of
      model input variables (substance, crop, and environmental properties) including
      their possible correlations using matrix algebra. We identified five key
      parameters responsible for between 80% and 93% of the variation in pesticide
      residues, namely time between substance application and crop harvest, degradation
      half-lives in crops and on crop surfaces, overall residence times in soil, and
      substance molecular weight. Partition coefficients also play an important role
      for fruit trees and tomato (Kow), potato (Koc), and lettuce (Kaw, Kow). Focusing
      on these parameters, we develop crop-specific models by parametrizing a complex
      fate and exposure assessment framework. The parametric models thereby reflect the
      framework's physical and chemical mechanisms and predict pesticide residues in
      harvest using linear combinations of crop, crop surface, and soil compartments.
      Parametric model results correspond well with results from the complex framework
      for 1540 substance-crop combinations with total deviations between a factor 4
      (potato) and a factor 66 (lettuce). Predicted residues also correspond well with
      experimental data previously used to evaluate the complex framework. Pesticide
      mass in harvest can finally be combined with reduction factors accounting for
      food processing to estimate human exposure from crop consumption. All parametric
      models can be easily implemented into existing assessment frameworks.

PMID- 23136827
TI  - Higher hepatic gene expression and serum levels of matrix metalloproteinase-2 are
      associated with steatohepatitis in non-alcoholic fatty liver diseases.
AB  - We investigated the gene expression of tissue inhibitor metalloproteinases
      (TIMPs) and matrix metalloproteinases (MMPs) and serum levels of TIMPs, MMPs, and
      hyaluronic acid that are associated with liver fibrosis in 64 patients with
      nonalcoholic fatty liver diseases (NAFLD). Whereas, no differences were found
      between patients with and without nonalcoholic steatohepatitis (NASH) in serum
      levels of hyaluronic acid when excluding NASH patients with advanced fibrosis,
      the quantity of MMP2 mRNA in liver tissue and serum MMP2 levels were
      significantly higher in patients with NASH than those without, even focusing on
      patients with less advanced fibrosis, indicating the initiation of liver
      fibrosis.

PMID- 23136828
TI  - Is there sufficient evidence to support the long-term efficacy of mineral
      trioxide aggregate (MTA) for endodontic therapy in primary teeth?
AB  - Several papers have been published to illustrate the effectiveness of mineral
      trioxide aggregate (MTA) as a pulpotomy medicament. Most of these reports do not
      offer a critical assessment on the data quality. Therefore, this review evaluated
      whether the currently available evidence is of an appropriate quality to support
      the long-term effectiveness of MTA as a pulpotomy medicament in primary molars
      using a standardized assessment criterion. A comprehensive literature search of
      human clinical outcome studies, which employed MTA as a pulpotomy medicament in
      primary teeth, was conducted using the MEDLINE database. Two independent
      observers rated these articles using the standardized assessment criteria.
      Furthermore, based on the initial sample mentioned in the individual studies and
      the sample included for the final analysis, the drop-out rates were calculated.
      Twenty-two studies were included for quality assessment with an excellent
      interobserver agreement. None of the 22 studies obtained grade A, four studies
      attained grade B1, five were graded B2 and 13 received grade C. Based on the
      assessment criteria employed, there was no evidence that MTA was better than
      present materials and techniques as a pulpotomy medicament. Furthermore, given
      the low quality of data, it is highly desirable to establish standard requisites
      for conducting and reporting on pulp therapy studies in primary teeth so as to
      benefit both researchers and clinicians to produce high-quality studies that are
      comparable and to prevent the misuse of clinical material and resources.

PMID- 23136829
TI  - Fluostatins I-K from the South China Sea-derived micromonospora rosaria SCSIO
      N160.
AB  - The strain SCSIO N160 was isolated from a South China Sea sediment sample and was
      characterized as a Micromonospora rosaria species on the basis of its 16S rRNA
      gene sequence. Three new fluostatins, I-K (1-3), were isolated from the culture
      of M. rosaria SCSIO N160, together with six known compounds, fluostatins C-F (4
      7), rabelomycin (8), and phenanthroviridone (9). The structure of fluostatin D
      (5) was confirmed by an X-ray crystallographic study. The absolute configuration
      of 1 and 3 was assigned by electronic circular dichroism calculations. Compounds
      8 and 9 exhibited good antimicrobial activities against Staphylococcus aureus
      ATCC 29213 with MIC values of 1.0 and 0.25 MUg/mL, respectively. Compound 9 also
      exhibited significant in vitro cytotoxic activities toward SF-268 (IC50 0.09 MUM)
      and MCF-7 (IC50 0.17 MUM). 

PMID- 23136830
TI  - Determinants of intention to get tested for STI/HIV among the Surinamese and
      Antilleans in the Netherlands: results of an online survey.
AB  - BACKGROUND: High infection rates of STIs are found among the different ethnic
      communities living in the Netherlands, especially among the Surinamese and Dutch
      Antilleans. Only limited effective interventions that promote STI/HIV testing
      among these communities are available in the Netherlands. In the present study we
      identified the determinants of the intention to get tested for STI/HIV of the
      sexually active Surinamese and Dutch-Antilleans living in the Netherlands.
      Secondly, this study assesses which determinants should be addressed when
      promoting STI/HIV testing among these communities. METHODS: In total, 450
      Surinamese and 303 Dutch-Antillean respondents were recruited through Dutch
      Internet panels and group activities. The questionnaire used in the online survey
      was based on the concepts of the Health Belief Model, the Social Cognitive
      Theory, and Theory of Planned behavior. To correct for multiple outcome testing,
      we considered differences as statistically significant at p<.01 for all analyses.
      For the multivariate linear regression analysis, variables that were significant
      were entered into the model block-wise. RESULTS: Health motivation, cues to
      action, subjective norms, risk behavior, test history, open communication about
      sexuality, and marital status were important (univariate) predictors of the
      intention to get tested for STI/HIV for both the Surinamese and Dutch-Antillean
      respondents. For both the Surinamese and Dutch-Antilleans, subjective norms were
      the most salient predictor of the intention to get tested in multivariate
      analyses, explaining 10% and 13% of the variance respectively; subjective norms
      had a direct influence on the intention for both the Surinamese and the Dutch
      Antilleans. CONCLUSIONS: The strong correlation and predictive power of
      subjective norms on the intention to get tested for STI/HIV, endorses the
      importance of focusing on community-based intervention rather than focusing on
      personal determinants, to change the present perceptions and attitudes towards
      testing. Health promoting programs should be aimed at promoting open
      communication regarding sexuality and testing. Stimulating each other to get
      tested frequently could also help achieving the desired behavior.

PMID- 23136831
TI  - Shiftworkers report worse sleep than day workers, even in retirement.
AB  - The aim of this study was to explore how the level of shiftwork exposure during
      an individual's working life might be related to subjectively reported sleep
      quality and timing during retirement. Telephone interviews regarding past
      employment and sleep timing and quality (among other variables) were conducted
      using a pseudo-random age-targeted sampling process. Subjective sleep quality was
      assessed using a telephone version of the Pittsburgh Sleep Quality Index. Timing
      of reported habitual bedtimes and rise-times were assessed using the Sleep Timing
      Questionnaire. Questions measuring morningness and subjective health were also
      given. Retired seniors (aged >65 years, n = 1113) were studied. Analysis was by
      analysis of variance, with shiftwork exposure in three bins [0 (n = 387), 1-15 (n
      = 371) and >15 years (n = 355)], gender (n = 634 male, 479 female) and former
      occupation [in two broad categories, 'managerial' (n = 437) versus 'other' (n =
      676)] as factors. In retired shiftworkers, relative to retired day workers, past
      exposure to shiftwork was associated with higher (worse) PSQI scores by 1.0 units
      (1-15 years) and 0.6 units (>15 years) (main effect P = 0.005). There were also
      main effects of gender and former occupation (males and managerials reporting
      better sleep), but neither variable interacted with shiftwork exposure. The
      timing of current mean habitual bedtimes and rise-times (and also the variance
      around them) were very similar for the three shiftwork exposure groups. The
      shiftwork exposure effect did not appear to be mediated by either morningness or
      current health. Prior exposure to shiftwork would appear to be related to
      currently reported sleep problems during retirement.

PMID- 23136832
TI  - Processing challenges with solid dosage formulations containing vitamin E TPGS.
AB  - The objective of this study is to investigate processing challenges associated
      with the incorporation of Vitamin E TPGS (d-alpha tocopheryl polyethylene glycol
      1000 succinate) into solid pharmaceutical dosage forms. For this work, a wet
      granulation process (high-shear and fluid bed) was used and Vitamin E TPGS was
      added as part of the binder solution during granulation. It was shown that
      Vitamin E TPGS can be incorporated into a prototype formulation at 10% w/w
      concentration without any significant processing challenges. However, the
      resulting granulations could only be compressed successfully at low tablet press
      speeds (dwell time ~100 ms). When compressed at low dwell times (<20 ms)
      representative of commercial tablet manufacturing, a significant loss in
      compactability was observed. In addition, several other tablet defects were
      observed. It was shown that intragranular incorporation of Aeroperl((r)) 300, a
      granulated form of colloidal silicon dioxide, was able to overcome these
      compaction problems. The formulation consisting of Aeroperl((r)) 300 showed
      significantly lower granule particle size, higher granule porosity and higher
      compactability as compared to the formulation without Aeroperl((r)) 300.

PMID- 23136833
TI  - Inconsistencies in clinical guidelines for obstetric anaesthesia for Caesarean
      section: a comparison of the Danish, English, American, and German guidelines
      with regard to developmental quality and guideline content.
AB  - BACKGROUND: Anaesthetists need evidence-based clinical guidelines, also in
      obstetric anaesthesia. We compared the Danish, English, American, and German
      national guidelines for anaesthesia for Caesarean section. We focused on
      assessing the quality of guideline development and evaluation of the guidelines'
      content. METHODS: We compared the four countries' guideline developmental quality
      by using the Appraisal of Guidelines for Research and Evaluation (AGREE)
      instrument, an international tool for development and assessment of guidelines.
      The clinically important content of these countries' guidelines was compared.
      RESULTS: We found differences in the quality of guideline development in the four
      countries. The German guidelines scored very low in the AGREE analysis, and the
      Danish national guideline scored low in the AGREE analysis. The American and
      British guideline both achieved high scores in the AGREE analysis. We found
      differences in the content of the four countries' guidelines. The Danish,
      American, and British guidelines were comprehensive but with some variation in
      the content. CONCLUSION: Development of national guidelines might benefit from
      following standardised regulations, such as those used in the AGREE tool. Content
      of guidelines is not standardised. Recommendations for the content of guidelines
      might contribute to standardising clinical guidelines.

PMID- 23136834
TI  - An open prospective study of amikacin pharmacokinetics in critically ill patients
      during treatment with continuous venovenous haemodiafiltration.
AB  - BACKGROUND: The objectives of the current study were to determine amikacin
      pharmacokinetics in patients undergoing treatment with continuous venovenous
      haemodiafiltration (CVVHDF) in an Intensive Care Unit (ICU), and to determine
      whether peak and trough concentration data could be used to predict
      pharmacokinetic parameters. An open prospective study was undertaken, comprising
      five critically ill patients with sepsis requiring CVVHDF. METHODS: Peak and
      trough plasma concentrations and multiple serum levels in a dosage interval were
      measured and the latter fitted to both a one- and two-compartment model. Blood
      and ultrafiltrate samples were collected and assayed for amikacin to calculate
      the pharmacokinetic parameters; total body clearance (TBC), elimination rate
      constant (k) and volume of distribution (Vd). The concentration of amikacin in
      ultrafiltrate was used to determine the clearance via CVVHDF. CVVHDF was
      performed at prescribed dialysate rates of 1-2l h-1 and ultrafiltration rate of
      2l h-1. Blood was pumped at 200ml/min using a Gambro blood pump and Hospal AN69HF
      haemofilter. Amikacin dosing was according to routine clinical practice in the
      Intensive Care Unit. RESULTS: The multi serum level study indicated that the one
      compartment model was adequate to characterize the pharmacokinetics in these
      patients suggesting that peak and trough plasma level data may be used to
      estimate individual patient pharmacokinetic parameters and to optimise individual
      patient dosing during treatment with CVVHDF. CVVHDF resulted in an amikacin k of
      0.109+/-0.025 h, t1/2 of 6.74 +/- 1.69h, TBC of 3.39+/-0.817 h-1, and Vd of 31.4
      +/- 3.27. The mean clearance due to CVVHDF of 2.86 l h-1 is similar to the
      creatinine clearance of 2.74 +/-0.4 lh-1. Amikacin was significantly cleared by
      CVVHDF, and its half life in patients on CVVHDF was approximately 2-3 times that
      reported in subjects without renal impairment and not undergoing
      haemodiafiltration for any reason. CONCLUSIONS: CVVHDF contributes significantly
      to total clearance of amikacin. The use of pharmacokinetic parameter estimates
      obtained from two steady state serum-drug concentrations (peak and trough) can be
      used to guide individualised dosing of critically ill patients treated with
      CVVHDF. This is considered a useful strategy in this patient cohort, particularly
      in avoiding the risk of underdosing.

PMID- 23136835
TI  - Q&A: what is regeneration, and why look to planarians for answers?

PMID- 23136836
TI  - Bevacizumab in combination with IFN-alpha in metastatic renal cell carcinoma: the
      AVOREN trial.
AB  - Metastatic renal cell carcinoma (mRCC) is tumor resistant to all cytotoxic
      agents. During the last decade, effective targeted therapies emerged including
      sunitinib, pazopanib and the combination of bevacizumab with IFN-alpha. The use
      of bevacizumab plus IFN-alpha combination in mRCC is supported by the AVOREN
      trial. Although the primary end point of the AVOREN trial was overall survival,
      progression-free survival was used to evaluate efficacy and served as the basis
      of regulatory submission owing to the advent of targeted agents that probably
      resulted in the prolongation of overall survival in both experimental and control
      arms. The doubling of median progression-free survival in the AVOREN trials (from
      5.4 to 10.2 months) is remarkably similar compared with the results of Phase III
      trials with sunitinib and pazopanib. Bevacizumab plus IFN-alpha is the only
      combined regimen currently used in mRCC and serves as a comparator in the trials
      combining bevacizumab with other agents.

PMID- 23136837
TI  - The risk of venous thrombosis in women over 50 years old using oral contraception
      or postmenopausal hormone therapy.
AB  - BACKGROUND: Oral contraception (OC) and postmenopausal hormone therapy (HT) can
      be used to alleviate menopausal symptoms. However, the risk of venous thrombosis
      (VT) associated with OC use in women over 50 years old has never been assessed
      and the two preparations have not been directly compared. OBJECTIVES: To
      determine and compare the risk of VT associated with OC and HT use. METHODS: From
      a large case-control study, 2550 women aged over 50 years old, 1082 patients with
      a first VT and 1468 controls, were included. Odds ratios (ORs) and 95% confidence
      intervals for VT were calculated for OC-users (164 patients and 54 controls) and
      HT-users (88 patients and 102 controls) compared with non-hormone users (823
      patients and 1304 controls). RESULTS: OC-users had a 6.3-fold (4.6-9.8) increased
      risk of VT. This ranged from 5.4 (3.3-8.9) for preparations containing
      levonorgestrel to 10.2 (4.8-21.7) for desogestrel. The VT-risk associated with
      oral HT use was 4.0 (1.8-8.2) for conjugated equine estrogen combined with
      medroxyprogesterone acetate and 3.9 (1.5-10.7) for micronized estradiol combined
      with norethisterone acetate. Non-oral HT did not increase the risk of VT: OR 1.1
      (0.6-1.8). Relative risk estimates were further increased in hormone users with
      factor V Leiden, prothrombin G20210A or blood group non-O and hormone users with
      a family history of VT. CONCLUSIONS: In this study, non-oral HT seemed to be the
      safest hormonal preparation in women over 50 years old. OC use increased the VT
      risk the most, especially in women with inherited thrombophilia or a family
      history of VT.

PMID- 23136838
TI  - A prospective, non comparative, multicenter study to investigate the effect of
      cadexomer iodine on bioburden load and other wound characteristics in diabetic
      foot ulcers.
AB  - Few studies regarding wound treatment with topical antimicrobials evaluate change
      in the bacterial bioburden of the wound with treatment. This study sought out to
      determine the in vivo effect of cadexomer iodine antibacterial dressing on
      diabetic foot ulcers (DFUs) that were infected or achieved a critical level of
      colonisation, looking specifically at wound progression in relation to bioburden.
      Fifteen patients corresponding to 16 total DFUs met criteria of displaying
      clinical signs of infection or critical colonisation and were suitable for a
      topical antibacterial dressing. They underwent weekly treatment for 6 weeks.
      Cultures were taken at week 0, 3 and 6 as appropriate. At week 6 median log10
      bacterial count reduction of 1.0 was observed from baseline (p = 0.025). At week
      3- a median log10 bacterial count reduction of 0.3 was observed from baseline (p
      = 0.049). Over the study period there was a 53.6% median reduction of the wound
      surface area. There were no patients that completely healed their ulcer over the
      6 week study period. There was a statistically significant median reduction in
      the bacterial load over the 6 week period (p = 0.025) as well as 3 weeks (p =
      0.049). This was accompanied by a median reduction of 53.6% in ulcer surface area
      and 50% in ulcer depth from baseline to final.

PMID- 23136840
TI  - A new criterion for confounder selection? Neither a confounder nor science.

PMID- 23136839
TI  - Zinc-finger nuclease mediated disruption of Rag1 in the LEW/Ztm rat.
AB  - BACKGROUND: Engineered zinc-finger nucleases (ZFN) represented an innovative
      method for the genome manipulation in vertebrates. ZFN introduced targeted DNA
      double strand breaks (DSB) and initiated non-homologous end joining (NHEJ) after
      pronuclear or cytoplasmatic microinjection into zygotes. Resulting frame shift
      mutations led to functional gene ablations in zebra fish, mice, pigs and also in
      laboratory rats. Therefore, we targeted the rat Rag1 gene essential for the V(D)J
      recombination within the immunoglobulin production process and for the
      differentiation of mature B and T lymphocytes to generate an immunodeficient rat
      model in the LEW/Ztm strain. RESULTS: After microinjection of Rag1 specific ZFN
      mRNAs in 623 zygotes of inbred LEW/Ztm rats 59 offspring were born from which one
      carried a 4 bp deletion. This frame shift mutation led to a premature stop codon
      and a subsequently truncated Rag1 protein confirmed by the loss of the full
      length protein in Western Blot analysis. Truncation of the Rag1 protein was
      characterized by the complete depletion of mature B cells. The remaining T cell
      population contained mature CD4+/CD3+/TCRalphabeta+ as well as
      CD8+/CD3+/TCRalphabeta+ positive lymphocytes accompanied by a compensatory
      increase of natural killer cells in the peripheral blood. Reduction of T cell
      development in Rag1 mutant rats was associated with a hypoplastic thymus that
      lacked follicular structures. Histological evaluation also revealed the near
      complete absence of lymphocytes in spleen and lymph nodes in the immunodeficient
      Rag1 mutant rat. CONCLUSION: The Rag1 mutant rat will serve as an important model
      for transplantation studies. Furthermore, it may be used as a model for
      reconstitution experiments related to the immune system, particularly with
      respect to different populations of human lymphocytes, natural killer cells and
      autoimmune phenomena.

PMID- 23136841
TI  - Objective and subjective socioeconomic gradients exist for sleep quality, sleep
      latency, sleep duration, weekend oversleep, and daytime sleepiness in adults.
AB  - Socioeconomic gradients exist for multiple health outcomes. Lower objective
      socioeconomic position (SEP), whether measured by income, education, or
      occupation, is associated with inadequate sleep. Less is known about whether
      one's perceived ranking of their social status, or subjective SEP, affects sleep.
      This study examined whether a subjective socioeconomic gradient exists for sleep
      while controlling for objective SEP. Participants (N = 177; age, M = 45.3 years,
      SD = 6.3 years) completed the Pittsburgh Sleep Quality Index, Epworth Sleepiness
      Scale, MacArthur Ladder, and other self-report measures to assess sleep and
      objective SEP. Subjective SEP trumped objective SEP as a better predictor of
      sleep duration, daytime sleepiness, and weekend oversleep. These findings
      highlight the need to expand our framework to better understand the mechanisms
      underlying socioeconomic gradients and sleep.

PMID- 23136842
TI  - Urinary lipid and protein oxidation products upon halothane, isoflurane, or
      sevoflurane anesthesia in humans: potential biomarkers for a subclinical
      nephrotoxicity.
AB  - OBJECTIVE: To investigate whether lipid and protein oxidation products are
      elevated and correlated with routine clinical markers of hepatic and renal
      function in patients anesthetized with halothane, isoflurane, or sevoflurane.
      METHODS: Urine and blood samples were collected from patient groups. Excretion of
      aldehydes, acetone, and o,o'-dityrosine was measured before and after anesthesia.
      Blood samples were analysed for clinical markers. RESULTS: Urinary concentrations
      of aldehydes, acetone, o,o'-dityrosine and glucose were significantly increased
      after anesthesia in halothane and sevoflurane groups earlier than clinical
      markers. Significant correlations were found in sevoflurane group. CONCLUSION:
      Lipid and protein oxidation contributes to subclinical sevoflurane
      nephrotoxicity. Oxidation products may serve as early biomarkers.

PMID- 23136843
TI  - Improving R&D productivity of pharmaceutical companies through public-private
      partnership: experiences from the Innovative Medicines Initiative.

PMID- 23136844
TI  - Real-time dissolution behavior of furosemide in biorelevant media as determined
      by UV imaging.
AB  - The potential of UV imaging as a new small scale flow-through dissolution testing
      platform and its ability to incorporate biorelevant media was tested. Furosemide
      was utilized as a model poorly soluble drug, and dissolution media simulating
      conditions in the small intestine (5/1.25 mM and 40/10 mM bile salt/phospholipid,
      pH 6.5) together with corresponding blank buffer were employed. Dissolution rates
      as a function of flow rate (0.2-1.0 mL/min) were determined directly from UV
      images, and by analysis of collected effluent using UV spectrophotometry. A good
      agreement in dissolution rates was observed, however repeatability of data based
      on measurement of collected effluent was superior to that obtained by UV imaging
      in the utilized prototypic flow cell. Both methods indicated that biorelevant
      media did not markedly increase the dissolution rate of furosemide as compared to
      buffer. Qualitatively, UV images indicated that uncontrolled
      swelling/precipitation of furosemide on the compact surface was occurring in some
      samples. In situ Raman spectroscopy together with X-ray diffraction analysis
      confirmed that the observations were not due to a solid form transformation of
      furosemide. The presented results highlight the complementary features of the
      utilized techniques and, in particular, the detailed information related to
      dissolution behavior which can be achieved by UV imaging. 

PMID- 23136845
TI  - Effects of potassium apigenin and verbena extract on the wound healing process of
      SKH-1 mouse skin.
AB  - Tissue repair is a complex process, which may be favoured or inhibited by
      different factors. Potassium apigenin (AP) and other flavonoids present in
      verbena extract (PLX((r)) ) possess powerful anti-inflammatory properties. The
      aim of this study was to evaluate the effects of topical treatment with AP and
      PLX gels on wounds inflicted on SKH-1/CRL mice. Forty-eight SKH-1 mice were used
      (4 groups with 12 animals each), which were subjected to wound excision with a
      round scalpel, 4 mm in diameter, on the dorsal skin. The animals were divided
      into four groups: Group I received topical applications of apigenin gel; Group II
      received PLX gel; Group III received vehicle gel; Group IV acted as control.
      Wound contraction, reepithelialisation, inflammation and neovascularisation (by
      means of immunohistochemical staining with anti-laminin) were recorded at study
      periods established at 2, 7 and 14 days. Reepithelialisation was faster in Groups
      I and II at 7 days (56.25% grade 3 and 43.75% grade 4) compared with the other
      groups. The degree of inflammation showed improvement with a tendency towards
      statistical significance in Groups I and II at 2 and 7 days. Anti-laminin
      staining was more intense in the group treated with PLX at the 2- and 7-day
      periods. Topical treatment with PLX gel improved the degree of
      reepithelialisation and inflammation, and favoured neo-vascularisation of the
      wounds at 2 and 7 days following surgery. 

PMID- 23136846
TI  - FungiQuant: a broad-coverage fungal quantitative real-time PCR assay.
AB  - BACKGROUND: Fungal load quantification is a critical component of fungal
      community analyses. Limitation of current approaches for quantifying the fungal
      component in the human microbiome suggests the need for new broad-coverage
      techniques. METHODS: We analyzed 2,085 18S rRNA gene sequences from the SILVA
      database for assay design. We generated and quantified plasmid standards using a
      qPCR-based approach. We evaluated assay coverage against 4,968 sequences and
      performed assay validation following the Minimum Information for Publication of
      Quantitative Real-Time PCR Experiments (MIQE) guidelines. RESULTS: We designed
      FungiQuant, a TaqMan(r) qPCR assay targeting a 351 bp region in the fungal 18S
      rRNA gene. Our in silico analysis showed that FungiQuant is a perfect sequence
      match to 90.0% of the 2,617 fungal species analyzed. We showed that FungiQuant's
      is 100% sensitive and its amplification efficiencies ranged from 76.3% to 114.5%,
      with r(2)-values of >0.99 against the 69 fungal species tested. Additionally,
      FungiQuant inter- and intra-run coefficients of variance ranged from <10% and
      <20%, respectively. We further showed that FungiQuant has a limit of
      quantification 25 copies and a limit of detection at 5 copies. Lastly, by
      comparing results from human-only background DNA with low-level fungal DNA, we
      showed that amplification in two or three of a FungiQuant performed in triplicate
      is statistically significant for true positive fungal detection. CONCLUSIONS:
      FungiQuant has comprehensive coverage against diverse fungi and is a robust
      quantification and detection tool for delineating between true fungal detection
      and non-target human DNA.

PMID- 23136847
TI  - Drinking before going to licensed premises: an event-level analysis of
      predrinking, alcohol consumption, and adverse outcomes.
AB  - BACKGROUND: Research in the United States and the United Kingdom indicates that
      drinking before going out (commonly called "predrinking") is common among young
      people and associated with increased harm. On the basis of Swiss data, this study
      investigates differences in alcohol consumption and adverse or risky outcomes for
      evenings when persons consumed alcohol before going to a licensed premise (i.e.,
      predrinking), drank on-premise only, or drank off-premise only. METHODS: Using
      the recently developed Internet-based cell phone-optimized assessment technique
      (ICAT), alcohol consumption and drinking location were assessed at 6 time points
      (5 pm to the next morning) on Thursdays, Fridays, and Saturdays over 5
      consecutive weeks by means of participants' cell phones. Overall, 7,828
      assessments provided by 183 young adults (53.0% women, mean age [SD] = 23.1
      [3.1]) on 1,441 evenings were analyzed by means of cluster-adjusted means and
      proportion tests and of multilevel structural equation models. The extent to
      which alcohol consumption mediated the association between predrinking and
      adverse outcomes was also examined. RESULTS: Higher alcohol consumption occurred
      on evenings with predrinking (7.1 drinks on average) compared with on-premise
      only (4.2 drinks) and off-premise only (4.3 drinks) evenings. Adverse outcomes
      occurred more often on evenings with predrinking (with 23.8% of predrinking
      nights involving at least 1 outcome) than on evenings with on-premise drinking
      only (13.9%) and off-premise drinking only (12.0%). Predrinking was indirectly
      associated with adverse outcomes, mediated by larger amounts of alcohol consumed
      in the evening. CONCLUSIONS: Because of its association with heavier consumption
      and related adverse outcomes, predrinking, especially combined with on-premise
      drinking, represents a major target for prevention. Educational interventions as
      well as structural measures, such as reduction in late-night off-sale opening
      hours, and staff training in responsible beverage service, are needed to prevent
      high total consumption and related adverse consequences among young people.

PMID- 23136848
TI  - The human leucocyte antigen DQB1*0602 allele is associated with
      electroencephelograph differences in individuals with obstructive sleep apnoea
      syndrome.
AB  - Human leucocyte antigen (HLA) DQB1*0602 allele, a well-known genetic risk factor
      for narcolepsy, has been associated with sleep parameters in healthy subjects. We
      aimed to assess the association of this allele with daytime sleepiness and
      altered sleep electroencephalogram characteristics in the general population and
      in patients with obstructive sleep apnoea syndrome (OSAS). Eight hundred and
      ninety-four individuals from the Epidemiologic Study of Sleep were genotyped for
      the HLA DQB1*0602 allele. Full-night polysomnography was performed, and daytime
      sleepiness was analysed according to the Epworth Sleepiness Scale. HLA-DQB1*0602
      allele-positive and -negative subjects in the general population, as well as in
      patients with OSAS, exhibited similar sleep parameters and levels of daytime
      sleepiness. However, spectral analysis showed that allele-positive individuals
      with OSAS exhibited higher theta power during sleep Stage 1 (P < 0.05) in
      occipital derivations, and lower delta power during sleep Stages 1 and 2 (P <
      0.01) compared with individuals negative for the allele, even after correction
      for potential confounders as age, sex, body mass index and European ancestry. No
      significant differences in the electroencephalogram variables were found in
      individuals without OSAS. The data highlight the HLA-DQB1*0602 as a potential
      genetic factor influencing sleep physiology in individuals diagnosed with OSAS.

PMID- 23136849
TI  - Designing biomaterials to direct stem cell fate.
AB  - As stem cells are a cornerstone of regenerative medicine, research efforts have
      been extensively focused on controlling their self-renewal and differentiation.
      It is well-known that stem cells are tightly regulated by a combination of
      physical and chemical factors from their complex extracellular surroundings;
      thus, conventional cell culture approaches based purely on using soluble factors
      to direct stem cell fate have resulted in limited success. To account for the
      complexities of native stem-cell niches, biomaterials are actively investigated
      as artificial extracellular matrices in order to mimic the natural
      microenvironment. This Perspective highlights important areas related to the
      design of biomaterials to control stem cell behavior, such as cell-responsive
      ligands, mechanical signals, and delivery of soluble factors.

PMID- 23136850
TI  - Role of surface exposed tryptophan as substrate generators for the antibody
      catalyzed water oxidation pathway.
AB  - The reaction of singlet oxygen with water to form hydrogen peroxide was catalyzed
      by antibodies and has been termed as the antibody catalyzed water oxidation
      pathway (ACWOP) (Nieva and Wentworth, Trends Biochem. Sci. 2004, 29, 274-278;
      Nieva et al. Immunol. Lett. 2006, 103, 33-38). While conserved and buried
      tryptophans in the antibody are thought to play a major role in this pathway, our
      studies with a monoclonal antibody, mAb-1 and its mutant W53A, clearly
      demonstrate the role of surface-exposed tryptophans in production of hydrogen
      peroxide, via the photo-oxidation pathway. Reactive oxygen species (ROS) such as
      singlet oxygen and superoxide were detected and site-specific tryptophan (Trp53)
      oxidation was observed under these conditions using RP-HPLC and mass
      spectrometry. The single mutant of the surface exposed Trp53 to Ala53 (W53A)
      results in a 50% reduction in hydrogen peroxide generated under these conditions,
      indicating that surface exposed tryptophans are highly efficient in transferring
      light energy to oxygen and contribute significantly to ROS generation. ACWOP
      potentially leads to the chemical instability of mAb-1 via the generation of ROS
      and is important to consider during clinical and pharmaceutical development of
      mAbs.

PMID- 23136851
TI  - Lost in transition: setting the psychosis threshold in prodromal research.

PMID- 23136852
TI  - A LuxR-type repressor of Burkholderia cenocepacia inhibits transcription via
      antiactivation and is inactivated by its cognate acylhomoserine lactone.
AB  - Burkholderia cenocepacia is an opportunistic human pathogen that encodes two LuxI
      type acylhomoserine lactone (AHL) synthases and three LuxR-type AHL receptors. Of
      these, cepI and cepR form a cognate synthase/receptor pair, as do cciI and cciR,
      while cepR2 lacks a genetically linked AHL synthase gene. Another group showed
      that a cepR2 mutant overexpressed a cluster of linked genes that appear to direct
      the production of a secondary metabolite. We found that these same genes were
      upregulated by octanoylhomoserine lactone (OHL), which is synthesized by CepI.
      These data suggest that several cepR2-linked promoters are repressed by CepR2 and
      that CepR2 is antagonized by OHL. Fusions of two divergent promoters to lacZ were
      used to confirm these hypotheses, and promoter resections and DNase I
      footprinting assays revealed a single CepR2 binding site between the two
      promoters. This binding site lies well upstream of both promoters, suggesting an
      unusual mode of repression. Adjacent to the cepR2 gene is a gene that we
      designate cepS, which encodes an AraC-type transcription factor. CepS is
      essential for expression of both promoters, regardless of the CepR2 status or OHL
      concentration. CepS therefore acts downstream of CepR2, and CepR2 appears to
      function as a CepS antiactivator.

PMID- 23136853
TI  - PET imaging of brain inflammation during early epileptogenesis in a rat model of
      temporal lobe epilepsy.
AB  - BACKGROUND: Recently, inflammatory cascades have been suggested as a target for
      epilepsy therapy. Positron emission tomography (PET) imaging offers the unique
      possibility to evaluate brain inflammation longitudinally in a non-invasive
      translational manner. This study investigated brain inflammation during early
      epileptogenesis in  the post-kainic acid-induced status epilepticus (KASE) model
      with post-mortem histology and in vivo with  [18F]-PBR111 PET. METHODS: Status
      epilepticus (SE) was induced (N = 13) by low-dose injections of KA, while
      controls (N = 9) received saline. Translocator protein (TSPO) expression and
      microglia activation were assessed with [125I]-CLINDE autoradiography and OX-42
      immunohistochemistry, respectively, 7 days post-SE. In a subgroup of rats, [18F]
      PBR111 PET imaging with metabolite-corrected input function was performed before
      post-mortem evaluation. [18F]-PBR111 volume of distribution (Vt) in volume of
      interests (VOIs) was quantified by means of kinetic modelling and a 
      VOI/metabolite-corrected plasma activity ratio. RESULTS: Animals with substantial
      SE showed huge overexpression of TSPO in vitro in relevant brain regions such as
      the hippocampus and amygdala (P < 0.001), while animals with mild symptoms
      displayed a smaller increase in TSPO in amygdala only (P < 0.001). TSPO
      expression was associated with OX-42 signal but without obvious cell loss.
      Similar in vivo [18F]-PBR111 increases in Vt and the simplified ratio were found
      in key regions such as the hippocampus (P < 0.05) and amygdala (P < 0.01).
      CONCLUSION: Both post-mortem and in vivo methods substantiate that the brain
      regions important in seizure generation display significant brain inflammation
      during epileptogenesis in the KASE model. This work enables future longitudinal
      investigation of the role of brain inflammation during epileptogenesis and
      evaluation of anti-inflammatory treatments.

PMID- 23136854
TI  - Sulfatase inhibitors: a patent review.
AB  - INTRODUCTION: Steroid sulfatase (STS) converts sulfated hormones to free hormones
      of importance in hormone-dependent diseases such as breast cancer and
      endometriosis. Carbohydrate sulfatases degrade complex carbohydrates as part of
      normal cellular turnover; certain lysosomal storage disorders (LSDs) involve
      defective processing of sulfated glycosaminoglycans by mutant sulfatases. AREAS
      COVERED: Aryl sulfamates have been developed as STS inhibitors, and STX64 and
      PGL2001 are under evaluation in Phase I and II clinical trials for treatment of
      endometrial and metastatic breast and prostate cancers and endometriosis. Dual
      acting compounds have emerged that are aromatase inhibitors (AIs), selective
      estrogen receptor antagonists, or inhibitors of microtubule polymerization.
      Sulfamidase inhibitors as pharmacological chaperones to assist maturation of
      folding-defective mutants for the treatment of Sanfilippo type A disease are
      under investigation. Coverage: The patent literature after the mid-1990s. EXPERT
      OPINION: The failure of STX64 in a Phase II monotherapy clinical trial should not
      dissuade further investigations in multidrug regimens, particularly in
      combination with AIs. The recent development of dual-acting compounds may enhance
      the potential for success in the clinic. Further investigations into aryl
      sulfamates are required to clarify the molecular mechanism of action;
      additionally, new reversible sulfatase inhibition concepts are needed for the
      development of pharmacological chaperones for sulfatase LSDs.

PMID- 23136855
TI  - Evaluation of yeasts obtained from Antarctic soil samples as biocontrol agents
      for the management of postharvest diseases of apple (Malus * domestica).
AB  - Psychrotrophic yeasts were isolated from Antarctic soils, selected based on their
      ability to grow in apple juice at low temperatures, and were evaluated as
      potential biocontrol agents for the management of postharvest diseases of apple
      during cold storage. Among the species recovered, an isolate of Leucosporidium
      scottii, designated At17, was identified as a good biocontrol agent for blue and
      gray mold of two apple cultivars. The selected isolate produced soluble and
      volatile antifungal substances that were inhibitory to apple pathogens.
      Siderophore production was also demonstrated, but it did not appear to play a
      role in pathogen inhibition. The selected yeast had the capacity to form a
      biofilm when grown in apple juice, which is considered an important attribute of
      postharvest antagonists to successfully colonize wounds and intact fruit
      surfaces. At17 was resistant to commonly used postharvest fungicides, so
      application of a combination of low-dose fungicide along with the biocontrol
      agent could be used as an integrated management practice.

PMID- 23136856
TI  - Oral miltefosine for Indian post-kala-azar dermal leishmaniasis: a randomised
      trial.
AB  - OBJECTIVE: Standard treatment of Indian post-kala-azar dermal leishmaniasis
      (PKDL) is unsatisfactory because to achieve therapeutic effectiveness, heroic
      courses of parenteral and toxic agents have to be administered. Our objective was
      to evaluate oral miltefosine for its potential to provide effective as well as
      tolerable treatment for this disease. METHOD: Open-label, randomised, parallel
      group multicentric trial. Miltefosine, 100 mg/day to all but one patient, was
      administered for 12 weeks or 8 weeks, with a target of 18 patients in each
      treatment group. Key endpoints were tolerance during treatment and efficacy at 12
      months of follow-up. RESULTS: The ITT and per-protocol cure rates after 12 months
      of follow-up for patients receiving 12 weeks of therapy were 78% (14 of 18
      patients: 95% CI = 61-88%) and 93% (14 of 15 patients: 95% CI = 71-95%),
      respectively, after 12 months of follow-up. The ITT and per-protocol cure rates
      for patients receiving 8 weeks of therapy were 76% (13 of 17 patients: 95% CI =
      53-90%) and 81% (13 of 16 patients: 95% CI = 57-93%), respectively.
      Gastrointestinal and other adverse events were rare. CONCLUSIONS: This study
      suggests that oral miltefosine for 2-3 months can be considered a treatment of
      choice for Indian PKDL.

PMID- 23136857
TI  - The effects of valence-based and discrete emotional states on aesthetic response.
AB  - There is increasing recognition that consumer aesthetics--the responses of
      consumers to the aesthetic or appearance aspects of products--has become an
      important area of marketing in recent years. Consumer aesthetic responses to a
      product are a source of pleasure for the consumer. Previous research into the
      aesthetic responses to products has often emphasized exterior factors and visual
      design, but studies have seldom considered the psychological aesthetic experience
      of consumers, and in particular their emotional state. This study attempts to
      bridge this gap by examining the link between consumers' emotions and their
      aesthetic response to a product. Thus, the major goal of this study was to
      determine how valence-based and discrete emotional states influence choice. In
      Studies 1 and 2, positive and negative emotions were manipulated to implement two
      different induction techniques and explore the effect of emotions on
      participants' choices in two separate experiments. The results of both
      experiments confirmed the predictions, indicating that aesthetic responses and
      purchase intention are functions of emotional valence, such that both are
      stronger for people in a positive emotional state than for those in a negative
      emotional state. Study 2 also used a neutral affective state to establish the
      robustness of this observed effect of incidental affect. The results of Study 3
      demonstrate that aesthetic response and purchase intention are not only a
      function of affect valence, but also are affected by the certainty appraisal
      associated with specific affective states. This research, therefore, contributes
      to the literature by offering empirical evidence that incidental affect is a
      determinant of aesthetic response.

PMID- 23136858
TI  - Greenhouse gas emissions for refrigerant choices in room air conditioner units.
AB  - In this work, potential replacement refrigerants for window-mounted room air
      conditioners (RACs) in the U.S. have been evaluated using a greenhouse gas (GHG)
      emissions analysis. CO(2)-equivalent emissions for several hydrofluoroethers
      (HFEs) and other potential replacements were compared to the most widely used
      refrigerants today. Included in this comparison are pure refrigerants that make
      up a number of hydrofluorocarbon (HFC) mixtures, pure hydrocarbons, and
      historically used refrigerants such as propane and ammonia. GHG emissions from
      direct and indirect sources were considered in this thermodynamic analysis.
      Propylene, dimethyl ether, ammonia, R-152a, propane, and HFE-152a all performed
      effectively in a 1 ton window unit and produced slightly lower emissions than the
      currently used R-22 and R-134a. The results suggest that regulation of HFCs in
      this application would have some effect on reducing emissions since end-of-life
      emissions remain at 55% of total refrigerant charge despite EPA regulations that
      mandate 80% recovery. Even so, offsite emissions due to energy generation
      dominate over direct GHG emissions and all the refrigerants perform similarly in
      totals of indirect GHG emissions.

PMID- 23136859
TI  - How do treatment-seeking overweight youth and their parents describe weight
      promoting factors in their family?
AB  - The aim of this pilot study is to describe youth and parents' perceptions of
      potential weight-promoting factors among families seeking treatment for youth
      overweight. We identified 2 important gaps in the vast multidisciplinary
      literature: (a) a lack of studies addressing both the youth and the parent
      perceptions about family factors that are potentially weight-promoting and (b) a
      lack of interventions that community health nurses could deliver specifically
      targeting families seeking treatment for overweight youth. Focus group data were
      content analyzed. Broad themes included: (a) mixed messages, (b) food and
      exercise as battleground, (c) problem solving, and (d) social aspects of youth
      overweight. We conclude that youth and parents could benefit from community
      health nursing interventions to implement healthcare professionals'
      recommendations incorporating all family members and creating and maintaining an
      accepting and demanding family climate.

PMID- 23136860
TI  - The association between unintended pregnancy and violence among incarcerated men
      and women.
AB  - BACKGROUND: In this article, we examine the association between unintended
      pregnancy and individual and community level indicators of violence in a
      population of both women and men in the criminal justice system. METHODS: We
      conducted a cross-sectional survey with 290 women and 306 men in 3 correctional
      facilities in Kansas City and used logistic regression models to assess
      relationships between key independent variables and unintended pregnancy.
      FINDINGS: In gender-specific logistic regression models, women with a history of
      intimate partner violence were 2.02 times more likely (CI 1.15, 3.56), and those
      with a history of sexual abuse before age 16 were 1.23 times more likely (CI 1.02
      1.49) to have experienced unintended pregnancy. Men or their family members who
      were victimized by neighborhood violence were 1.82 times more likely to have
      experienced unintended pregnancy (CI 1.01, 3.28). DISCUSSION: These findings
      suggest the need for gender and community-specific interventions that address the
      relationship between violence and unintended pregnancy.

PMID- 23136861
TI  - Health status of migrant farmworkers in the Shenandoah Valley.
AB  - The purpose of this study is to describe the characteristics and health status of
      a sample of migrant farmworkers in the Shenandoah Valley. The methodology for
      this study is a retrospective record review and analysis of data on 390 male
      migrant farmworkers. The group included men from Mexico (57. 2%), Jamaica (26.
      9%), and Haiti (13. 0%) with a mean age of 38.5 years. The most common health
      problems reported were work-related and included musculoskeletal pain, irritated
      eyes, and respiratory symptoms. This study identifies areas for community and
      public health nurses to target interventions to address health promotion/disease
      prevention efforts.

PMID- 23136862
TI  - Worries of independent older people regarding health and daily life: a survey of
      residents of a rural town in Japan.
AB  - The purpose of the study was to analyze the worries of independent older people
      regarding health and daily life. We collected data from 259 people who responded
      to the free descriptive questionnaire and analyzed it qualitatively and
      inductively. Thirteen categories derived from the results were classified into 6
      types of worries: health worries, life function worries, daily life worries, long
      term care worries, family relationship worries, and future life worries.
      Promoting the prevention of "long-term care status," the need for physical
      nursing care, in a super aging society, where the population of 65 years or older
      is more than 21% of all of the population, requires consideration of not only
      measures to deal with physical symptoms, but also measures to deal with
      psychological aspects, and social aspects.

PMID- 23136863
TI  - Household air pollution from cooking fires: a challenge for nurses globally and a
      call to action.
AB  - The global burden of disease from exposure to household air pollution related to
      cooking fires is ranked as the 6th leading cause of death, primarily impacting
      poor women and children in low-income countries. Globally, smoke exposure from
      household air pollution is attributed to approximately 1/3 of chronic obstructive
      pulmonary deaths, 1/4 of pneumonia deaths, and 3% of lung cancer deaths. Nurses
      are increasingly working in global health arenas but are typically ill-prepared
      to address this complex environmental health problem. Nurses can play a key role
      in education, practice, and research to develop and support interventions, both
      in the United States and abroad, which may reduce this substantial burden of
      disease.

PMID- 23136867
TI  - Conformers of CL-20 explosive and ab initio refinement using perturbation theory:
      implications to detonation mechanisms.
AB  - We have identified the major conformers of CL-20 explosive, otherwise known as
      2,4,6,8,10,12-hexanitrohexaazaisowurtzitane, more formally known as 2,4,6,8,10,12
      hexanitrohexaazatetracyclo[5.5.0.0]-dodecane, via Monte Carlo search in
      conformational space through molecular mechanics and subsequent quantum
      mechanical refinement using perturbation theory. Our search produced enough
      conformers to account for all of the various forms of CL-20 found in crystals.
      This suggests that our methodology will be useful in studying the conformational
      landscape of other nitramines. The energy levels of the conformers found are all
      within 0.25 eV of one another based on MBPT(2)/6-311G(d,p); consequently, without
      further refinement from a method such as coupled cluster theory, all conformers
      may reasonably be populated at STP in the gas phase. We also report the harmonic
      vibrational frequencies of conformers, including the implications on the
      mechanism of detonation. In particular, we establish that the weakest N-N
      nitramine of CL-20 is the cyclohexane equatorial nitramine. This preliminary
      mapping of the conformers of CL-20 makes it possible to study the mechanism of
      detonation of this explosive rigorously in future work.

PMID- 23136868
TI  - Prognostic value of KRAS genotype in metastatic colorectal cancer (MCRC) patients
      treated with intensive triplet chemotherapy plus bevacizumab (FIr-B/FOx)
      according to extension of metastatic disease.
AB  - BACKGROUND: Bevacizumab (BEV) plus triplet chemotherapy can increase efficacy of
      first-line treatment of metastatic colorectal cancer (MCRC), particularly
      integrated with secondary liver surgery in liver-limited (L-L) patients. The
      prognostic value of the KRAS genotype in L-L and other or multiple metastatic
      (O/MM) MCRC patients treated with the FIr-B/FOx regimen was retrospectively
      evaluated. METHODS: Tumoral and metastatic samples were screened for KRAS codon
      12 and 13 and BRAF mutations by SNaPshot and/or direct sequencing. Fit MCRC
      patients <75 years were consecutively treated with FIr-B/FOx regimen: weekly 12-h
      timed flat-infusion/5-fluorouracil (TFI 5-FU) 900 mg/m2, days 1, 2, 8, 9, 15, 16,
      22 and 23; irinotecan (CPT-11) 160 mg/m2 plus BEV 5 mg/kg, days 1, 15;
      oxaliplatin (OXP) 80 mg/m2, days 8, 22; every 4 weeks. MCRC patients were
      classified as L-L and O/MM. Activity and efficacy were evaluated and compared
      using log-rank test. RESULTS: In all, 59 patients were evaluated: 31 KRAS wild
      type (53%), 28 KRAS mutant (47%). At 21.5 months median follow-up, objective
      response rate (ORR), progression-free survival (PFS) and overall survival (OS)
      were, respectively: KRAS wild-type 90%, 14 months, 38 months; KRAS mutant 67%, 11
      months, 20 months. PFS and OS were not significantly different. PFS and OS were
      significantly different in L-L compared to O/MM evaluable patients. In KRAS wild
      type patients, clinical outcome of 12 L-L compared to 18 O/MM was significantly
      different: PFS 21 versus 12 months and OS 47 versus 28 months, respectively. In
      KRAS mutant patients, the clinical outcome of 13 L-L compared to 14 O/MM was not
      significantly different: PFS 11 months equivalently and OS 39 versus 19 months,
      respectively. CONCLUSIONS: The KRAS genotype wild-type and mutant does not
      significantly affect different clinical outcomes for MCRC patients treated with
      the first-line FIr-B/FOx intensive regimen. KRAS wild-type patients with L-L
      disease may achieve a significantly prolonged clinical outcome due to integration
      with secondary liver surgery, with respect to KRAS mutant patients.

PMID- 23136869
TI  - Interactions of age and cognitive functions in predicting decision making under
      risky conditions over the life span.
AB  - Little is known about how normal healthy aging affects decision-making
      competence. In this study 538 participants (age 18-80 years) performed the Game
      of Dice Task (GDT). Subsamples also performed the Iowa Gambling Task as well as
      tasks measuring logical thinking and executive functions. In a moderated
      regression analysis, the significant interaction between age and executive
      components indicates that older participants with good executive functioning
      perform well on the GDT, while older participants with reduced executive
      functions make more risky choices. The same pattern emerges for the interaction
      of age and logical thinking. Results demonstrate that age and cognitive functions
      act in concert in predicting the decision-making performance.

PMID- 23136870
TI  - Antifatigue activities of loach protein hydrolysates with different antioxidant
      activities.
AB  - The antioxidant and antifatigue activities of two peptides of <5 kDa were
      determined, that is, loach peptide A (LPA, from a papain digestion) and loach
      peptide B (LPB, from a Flavorzyme digestion). Their degrees of hydrolysis were 21
      +/- 0.21 and 35 +/- 0.32%, respectively. LPA fraction mainly possessed peptides
      of 1000 < MW < 3000 Da (65.41%), whereas LPB mainly possessed peptides of 500 <
      MW < 1000 Da (58.27%). LPA fraction contained 116.3 mg amino acid residues/g
      loach peptide powder of branched-chain amino acids, 1.42-fold that in LPB. LPA
      had stronger in vitro antioxidant activity than LPB. Compared with LPB, LPA
      increased swimming time more effectively and reduced blood urea nitrogen (BUN)
      and liver malonaldehyde (MDA) levels in mice, although both of them had
      significant antifatigue effects compared to the control (P < 0.05). Pearson
      correlation analysis showed that the antifatigue activity of loach peptide was
      highly correlated with its antioxidant activities.

PMID- 23136871
TI  - Malate metabolism in Bacillus subtilis: distinct roles for three classes of
      malate-oxidizing enzymes.
AB  - The Gram-positive soil bacterium Bacillus subtilis uses glucose and malate as the
      preferred carbon sources. In the presence of either glucose or malate, the
      expression of genes and operons for the utilization of secondary carbon sources
      is subject to carbon catabolite repression. While glucose is a preferred
      substrate in many organisms from bacteria to man, the factors that contribute to
      the preference for malate have so far remained elusive. In this work, we have
      studied the contribution of the different malate-metabolizing enzymes in B.
      subtilis, and we have elucidated their distinct functions. The malate
      dehydrogenase and the phosphoenolpyruvate carboxykinase are both essential for
      malate utilization; they introduce malate into gluconeogenesis. The NADPH
      generating malic enzyme YtsJ is important to establish the cellular pools of
      NADPH for anabolic reactions. Finally, the NADH-generating malic enzymes MaeA,
      MalS, and MleA are involved in keeping the ATP levels high. Together, this unique
      array of distinct activities makes malate a preferred carbon source for B.
      subtilis.

PMID- 23136872
TI  - Osteochondral defects of the talus: a novel animal model in the goat.
AB  - Osteochondral defects of the talus pose a difficult therapeutic challenge. An
      experimental animal model of the ankle joint is not available. The aim of this
      study was to test a newly developed animal model for osteochondral defects of the
      ankle in vivo. Osteochondral defects were created in the talus of goat hind legs
      using a posterolateral surgical approach. The defects were filled with either
      autologous cancellous bone or donor demineralized bone matrix or left empty as
      control. After 12 weeks of healing, the specimens were analyzed with radiography,
      macroscopy, microcomputed tomography, histology, histomorphometry, and
      fluorescence microscopy. It was possible to create a standardized defect in each
      talus. The implanted material remained in place. The analyses showed that most
      bony tissue was generated in the defects filled with autologous bone and least in
      the control defects. Our findings show that a standard osteochondral defect can
      be created in the talus by a relatively simple procedure in a large animal that
      allows qualitative and quantitative evaluation. The model can be used in future
      experiments to investigate alternative treatment methods before they are
      introduced into clinical practice.

PMID- 23136873
TI  - The effects of natural variation in background radioactivity on humans, animals
      and other organisms.
AB  - Natural levels of radioactivity on the Earth vary by more than a thousand-fold;
      this spatial heterogeneity may suffice to create heterogeneous effects on
      physiology, mutation and selection. We review the literature on the relationship
      between variation in natural levels of radioactivity and evolution. First, we
      consider the effects of natural levels of radiation on mutations, DNA repair and
      genetics. A total of 46 studies with 373 effect size estimates revealed a small,
      but highly significant mean effect that was independent of adjustment for
      publication bias. Second, we found different mean effect sizes when studies were
      based on broad categories like physiology, immunology and disease frequency; mean
      weighted effect sizes were larger for studies of plants than animals, and larger
      in studies conducted in areas with higher levels of radiation. Third, these
      negative effects of radiation on mutations, immunology and life history are
      inconsistent with a general role of hormetic positive effects of radiation on
      living organisms. Fourth, we reviewed studies of radiation resistance among taxa.
      These studies suggest that current levels of natural radioactivity may affect
      mutational input and thereby the genetic constitution and composition of natural
      populations. Susceptibility to radiation varied among taxa, and several studies
      provided evidence of differences in susceptibility among populations or strains.
      Crucially, however, these studies are few and scattered, suggesting that a
      concerted effort to address this lack of research should be made.

PMID- 23136875
TI  - First trimester in utero exposure to methylphenidate.
AB  - Methylphenidate is a centrally acting sympathomimetic used for the treatment of
      attention deficit/hyperactivity disorder in children and adolescents and for
      narcolepsy in adults. Despite the growing use among adult women, no reliable data
      on the prevalence of use during pregnancy have been published, and safety during
      pregnancy has not been established. We systematically reviewed available data on
      birth outcome after human in utero exposure to methylphenidate. Systematic
      searches in PubMed/Embase were performed from origin to August 2012, and data
      from Michigan Medicaid recipients, The Collaborative Perinatal Project and the
      Swedish Birth Registry were evaluated. Excluding three case reports, a total of
      180 children exposed to methylphenidate in utero during first trimester were
      identified, among whom, four children with major malformations were observed.
      Methylphenidate exposure during pregnancy does not appear to be associated with a
      substantially (i.e. more than twofold) increased risk of congenital
      malformations.

PMID- 23136874
TI  - Biomarkers of peripheral muscle fatigue during exercise.
AB  - BACKGROUND: Biomarkers of peripheral muscle fatigue (BPMFs) are used to offer
      insights into mechanisms of exhaustion during exercise in order to detect
      abnormal fatigue or to detect defective metabolic pathways. This review aims at
      describing recent advances and future perspectives concerning the most important
      biomarkers of muscle fatigue during exercise. RESULTS: BPMFs are classified
      according to the mechanism of fatigue related to adenosine-triphosphate
      metabolism, acidosis, or oxidative-metabolism. Muscle fatigue is also related to
      an immunological response. impaired calcium handling, disturbances in
      bioenergetic pathways, and genetic responses. The immunological and genetic
      response may make the muscle susceptible to fatigue but may not directly cause
      muscle fatigue. Production of BPMFs is predominantly dependent on the type of
      exercise. BPMFs need to change as a function of the process being monitored, be
      stable without appreciable diurnal variations, correlate well with exercise
      intensity, and be present in detectable amounts in easily accessible biological
      fluids. The most well-known BPMFs are serum lactate and interleukin-6. The most
      widely applied clinical application is screening for defective oxidative
      metabolism in mitochondrial disorders by means of the lactate stress test. The
      clinical relevance of most other BPMFs, however, is under debate, since they
      often depend on age, gender, physical fitness, the energy supply during exercise,
      the type of exercise needed to produce the BPMF, and whether healthy or diseased
      subjects are investigated. CONCLUSIONS: Though the role of BPMFs during fatigue
      is poorly understood, measuring BPMFs under specific, standardised conditions
      appears to be helpful for assessing biological states or processes during
      exercise and fatigue.

PMID- 23136876
TI  - The global response of Nostoc punctiforme ATCC 29133 to UVA stress, assessed in a
      temporal DNA microarray study.
AB  - Cyanobacteria in nature are exposed not only to the visible spectrum of sunlight
      but also to its harmful ultraviolet components (UVA and UVB). We used Nostoc
      punctiforme ATCC 29133 as a model to study the UVA response by analyzing global
      gene expression patterns using genomic microarrays. UVA exposure resulted in the
      statistically detectable differential expression of 573 genes of the 6903 that
      were probed, compared with that of the control cultures. Of those genes, 473 were
      up-regulated, while only 100 were down-regulated. Many of the down-regulated
      genes were involved in photosynthetic pigment biosynthesis, indicating a
      significant shift in this metabolism. As expected, we detected the up-regulation
      of genes encoding antioxidant enzymes and the sunscreen, scytonemin. However, a
      majority of the up-regulated genes, 47%, were unassignable bioinformatically to
      known functional categories, suggesting that the UVA stress response is not well
      understood. Interestingly, the most dramatic up-regulation involved several
      contiguous genes of unassigned metabolism on plasmid A. This is the first global
      UVA stress response analysis of any phototrophic microorganism and the
      differential expression of 8% of the genes of the Nostoc genome indicates that
      adaptation to UVA in Nostoc has been an evolutionary force of significance.

PMID- 23136877
TI  - The mediating role of alcohol-related memory associations on the relation between
      perceived parental drinking and the onset of adolescents' alcohol use.
AB  - AIMS: The aim of the current study was to examine the mediating role of alcohol
      related memory associations in the relation between perceived parental drinking
      and the onset of adolescents' alcohol use. Gender and grade were also included in
      the analyses. DESIGN: We tested a mediation model within a structural path
      modelling framework using longitudinal data (two waves). SETTING AND
      PARTICIPANTS: The sample consisted of 608 Canadian adolescents (42.9% boys), who
      did not have any alcohol experiences at the first measurement. The adolescents
      were recruited from all grades 7-9 classes in a large school district in western
      Canada. MEASUREMENTS: Alcohol-related memory associations were tested with the
      Word Association Test. We used adolescent self-reports of alcohol use and
      parental drinking. FINDINGS: Results clearly showed a mediation effect of alcohol
      related memory associations [estimate = 0.023, 95% confidence interval (CI):
      0.002-0.044). That is, parental drinking as perceived by the adolescent was
      related positively to alcohol-related memory associations, which in turn
      predicted adolescents' alcohol use a year later. Gender and grade were related to
      alcohol-related memory associations. That is, boys and adolescents of higher
      grades had more memory associations. CONCLUSIONS: Children appear to form memory
      associations related to alcohol before they ever drink alcohol themselves, and
      these associations appear to mediate the link between their perceptions of their
      parents' drinking and their own initial alcohol use.

PMID- 23136878
TI  - Impulsivity and motivations to consume alcohol: a prospective study on risk of
      dependence in young adult women.
AB  - BACKGROUND: Increasing numbers of emerging adult women are engaging in heavy
      drinking behavior, placing them at risk of negative outcomes and alcohol use
      disorders (AUDs). The purpose of this study was to examine the influence of 5
      pathways to impulsive behavior (negative urgency [NU], positive urgency, lack of
      deliberation [DEL], lack of persistence, and sensation seeking), drinking
      motives, and their interaction on increases in symptoms of alcohol dependence in
      young adult women in a prospective design. METHODS: Zero-inflated Poisson
      regression models were used to examine the influence of traits, motives, and
      their interaction at baseline on increases in symptoms of AUDs approximately 3
      months later. A total of 319 first semester college women completed the first
      wave of the study; 235 of these were drinkers. RESULTS: Among drinkers, 17% of
      the sample reported increases in S-MAST scores over the study period. Consistent
      with hypotheses, the interaction of NU and coping motives, as well as DEL and
      enhancement motives predicted increase in dependence symptoms at Time 2.
      CONCLUSIONS: This is one of very few studies to examine the influence of
      impulsivity-related traits and drinking motives on alcohol dependence symptoms
      prospectively in a sample of emerging adult women. We found that NU and (lack of)
      deliberation were predictors of such increases. Our hypothesis that women who
      endorsed both high levels of NU and high baseline endorsement of coping motives
      would have the most increases in symptoms over time was also supported.

PMID- 23136879
TI  - Psychopathological long-term outcome of schizophrenia -- a review.
AB  - OBJECTIVE: In the past, the comparability of empirical studies that examined the
      course and outcome of schizophrenia was limited by their use of different
      diagnostic systems. Focussing on the psychopathological long-term outcome, the
      present article aims to review follow-up studies that used modern operationalized
      diagnostic criteria for schizophrenia (DSM-III, DSM-III-R, DSM-IV and ICD-10).
      METHOD: We searched MEDLINE, the Cochrane Central Register of Controlled Trials,
      EMBASE, PsycINFO and PSYNDEX for relevant studies up to the year 2011. Twenty-one
      studies were included in the final analysis. RESULTS: The long-term outcome of
      schizophrenia was heterogeneous and included full remissions as well as severe
      chronic states. Schizophrenia, however, showed a considerably more unfavourable
      outcome than other diagnostic groups such as schizoaffective or affective
      disorders. Psychopathological symptoms remained relatively stable in the course
      of illness. Several predictors for a poor outcome were identified, such as male
      gender or pronounced negative symptoms. CONCLUSION: Recent studies using modern
      diagnostic systems largely confirm the results of earlier studies. Current
      diagnostic criteria for schizophrenia identify a heterogeneous sample of
      patients. The influence of therapeutic interventions on long-term outcome remains
      unclear.

PMID- 23136880
TI  - Modulating proximal cell signaling by targeting Btk ameliorates humoral
      autoimmunity and end-organ disease in murine lupus.
AB  - INTRODUCTION: Systemic lupus erythematosus is a chronic autoimmune disease
      characterized by an abundance of autoantibodies against nuclear antigens.
      Bruton's tyrosine kinase (Btk) is a proximal transducer of the BCR signal that
      allows for B-cell activation and differentiation. Recently, selective inhibition
      of Btk by PCI-32765 has shown promise in limiting activity of multiple cells
      types in various models of cancer and autoimmunity. The aim of this study was to
      determine the effect of Btk inhibition by PCI-32765 on the development of lupus
      in lupus-prone B6.Sle1 and B6.Sle1.Sle3 mice. METHODS: B6.Sle1 or B6.Sle1.Sle3
      mice received drinking water containing either the Btk inhibitor PCI-32765 or
      vehicle for 56 days. Following treatment, mice were examined for clinical and
      pathological characteristics of lupus. The effect of PCI-32765 on specific cell
      types was also investigated. RESULTS: In this study, we report that Btk
      inhibition dampens humoral autoimmunity in B6.Sle1 monocongenic mice. Moreover,
      in B6.Sle1.Sle3 bicongenic mice that are prone to severe lupus, Btk inhibition
      also dampens humoral and cellular autoimmunity, as well as lupus nephritis.
      CONCLUSIONS: These findings suggest that partial crippling of cell signaling in B
      cells and antigen presenting cells (APCs) may be a viable alternative to total
      depletion of these cells as a therapeutic modality for lupus.

PMID- 23136881
TI  - Dual role of HupF in the biosynthesis of [NiFe] hydrogenase in Rhizobium
      leguminosarum.
AB  - BACKGROUND: [NiFe] hydrogenases are enzymes that catalyze the oxidation of
      hydrogen into protons and electrons, to use H2 as energy source, or the
      production of hydrogen through proton reduction, as an escape valve for the
      excess of reduction equivalents in anaerobic metabolism. Biosynthesis of [NiFe]
      hydrogenases is a complex process that occurs in the cytoplasm, where a number of
      auxiliary proteins are required to synthesize and insert the metal cofactors into
      the enzyme structural units. The endosymbiotic bacterium Rhizobium leguminosarum
      requires the products of eighteen genes (hupSLCDEFGHIJKhypABFCDEX) to synthesize
      an active hydrogenase. hupF and hupK genes are found only in hydrogenase clusters
      from bacteria expressing hydrogenase in the presence of oxygen. RESULTS: HupF is
      a HypC paralogue with a similar predicted structure, except for the C-terminal
      domain present only in HupF. Deletion of hupF results in the inability to process
      the hydrogenase large subunit HupL, and also in reduced stability of this subunit
      when cells are exposed to high oxygen tensions. A DeltahupF mutant was fully
      complemented for hydrogenase activity by a C-terminal deletion derivative under
      symbiotic, ultra low-oxygen tensions, but only partial complementation was
      observed in free living cells under higher oxygen tensions (1% or 3%). Co
      purification experiments using StrepTag-labelled HupF derivatives and mass
      spectrometry analysis indicate the existence of a major complex involving HupL
      and HupF, and a less abundant HupF-HupK complex. CONCLUSIONS: The results
      indicate that HupF has a dual role during hydrogenase biosynthesis: it is
      required for hydrogenase large subunit processing and it also acts as a chaperone
      to stabilize HupL when hydrogenase is synthesized in the presence of oxygen.

PMID- 23136882
TI  - Severe mental illness at ART initiation is associated with worse retention in
      care among HIV-infected Ugandan adults.
AB  - OBJECTIVE: The impact of severe mental illness (SMI) on retention in HIV care
      remains uncertain. We aimed to measure the association between SMI at
      antiretroviral therapy (ART) initiation and subsequent retention in care in HIV
      infected Ugandan adults. METHOD: We conducted cohort study of 773 patients who
      initiated ART between January 2005 and July 2009 at the Butabika HIV clinic in
      Kampala, Uganda. SMI was defined as any clinically diagnosed organic brain
      syndrome, affective disorder or psychotic disorder. We used Kaplan-Meier and Cox
      proportional hazards analysis to evaluate the association between SMI and
      retention in care. RESULTS: The prevalence of SMI at ART initiation was 23%.
      Patients with SMI at baseline were similar to those without SMI in terms of age
      (median [IQR]: 35 [28-40] vs. 35 [30-40], P = 0.03), sex (36% vs. 35% female, P =
      0.86) and baseline CD4+ T-cell count (112 [54-175] vs. 120 [48-187] cells/mm3, P
      = 0.86). At 12 months after ART initiation, Kaplan-Meier estimates of continuous
      retention in care were 65% (95% confidence interval, CI: 31-39%) among patients
      without SMI, vs. 47% (95% CI: 39-55%) among those with SMI (P < 0.001). All-cause
      mortality in the two groups was similar: 1.2% vs. 2.0% (P > 0.05). In
      multivariable analysis, the only baseline variable independently associated with
      breakage of continuous care was SMI (HR = 1.58, 95% CI: 1.06?2.33). CONCLUSIONS:
      Severe mental illness at ART initiation is associated with worse retention in HIV
      care in this urban Ugandan referral hospital. As ART is scaled up across sub
      Saharan Africa, greater attention must be paid to the burden of mental illness
      and its impact on retention in care.

PMID- 23136883
TI  - ATR-FTIR spectroscopy study of the influence of pH and contact time on the
      adhesion of Shewanella putrefaciens bacterial cells to the surface of hematite.
AB  - Attachment of live cells of Shewanella putrefaciens strain CN-32 to the surface
      of hematite (alpha-Fe(2)O(3)) was studied with in situ ATR-FTIR spectroscopy at
      variable pH (4.5-7.7) and contact times up to 24 h. The IR spectra indicate that
      phosphate based functional groups on the cell wall play an important role in
      mediating adhesion through formation of inner-sphere coordinative bonds to
      hematite surface sites. The inner-sphere attachment mode of microbial P groups
      varies with pH, involving either a change in protonation or in coordination to
      hematite surface sites as pH is modified. At all pH values, spectra collected
      during the early stages of adhesion show intense IR bands associated with
      reactive P-groups, suggestive of preferential coordination of P-moieties at the
      hematite surface. Spectra collected after longer sorption times show distinct
      frequencies from cell wall protein and carboxyl groups, indicating that bacterial
      adhesion occurring over longer time scales is to a lesser degree associated with
      preferential attachment of P-based bacterial functional groups to the hematite
      surface. The results of this study demonstrate that pH and reaction time
      influence cell-mineral interactions, implying that these parameters play an
      important role in determining cell mobility and biofilm formation in aqueous
      geochemical environments.

PMID- 23136884
TI  - A family of secreted pathogenesis-related proteins in Candida albicans.
AB  - Analysing culture supernatants of yeast and hyphal cells of Candida albicans, we
      found two close homologues of pathogenesis-related (PR-) 1 proteins, Rbe1p and
      Rbt4p, in the secretome. Due to sequence homology, three additional, yet not
      characterized open reading frames, ORF19.6200, ORF19.2787 and ORF19.2336,
      together with RBE1 and RBT4 were assigned to a novel family of CaPRY proteins. In
      a Deltarbe1/Deltarbt4 deletion strain, genome-wide transcriptional analysis
      revealed differential transcription of only a limited set of genes implicated in
      virulence and oxidative stress response. Single deletion of RBE1 or RBT4 in a
      clinical C. albicans isolate resulted in a moderate but significant attenuation
      in virulence in a mouse model for disseminated candidiasis. However, a
      synergistic effect was observed in a Deltarbe1/Deltarbt4 double deletion strain,
      where virulence was strongly affected. Remarkably, transcription of RBT4 and RBE1
      was each upregulated in blastospores of Deltarbe1 or hyphae of Deltarbt4 deletion
      strains respectively, indicating functional complementation thereby compensating
      a potential virulence defect in the single deletion strains. Furthermore, the
      double deletion strain showed increased sensitivity to attack by
      polymorphonuclear leucocytes. Therefore, the crucial contribution of both C.
      albicans pathogenesis-related proteins to virulence might be vested in protection
      against phagocyte attack.

PMID- 23136886
TI  - Direct AMP-activated protein kinase activators: a review of evidence from the
      patent literature.
AB  - INTRODUCTION: AMP-activated protein kinase (AMPK), a heterotrimeric protein
      complex with serine/threonine kinase activity has a central role in controlling
      cellular energy expenditure. Small molecule-based activation of AMPK represents
      an attractive therapeutic proposition because of AMPK's ability to regulate
      several anabolic and catabolic pathways that are critical to the development of
      metabolic disorders and cancer. AREAS COVERED: A comprehensive review of
      published patents that disclose direct AMPK activators is provided: 26 patents
      comprising 10 chemical classes, and supporting in vitro and in vivo data are
      discussed. EXPERT OPINION: AMPK activation holds promise as a possible
      pharmacological intervention in several disease states. The development of
      direct, highly specific AMPK activators is necessary to fully realize the
      opportunities linked to AMPK activation and appreciate the risks associated with
      it.

PMID- 23136887
TI  - True and intentionally fabricated memories.
AB  - The aim of the experiment reported here was to investigate the processes
      underlying the construction of truthful and deliberately fabricated memories.
      Properties of memories created to be intentionally false (fabricated memories)
      were compared to properties of memories believed to be true (true memories).
      Participants recalled and then wrote or spoke true memories and fabricated
      memories of everyday events. It was found that true memories were reliably more
      vivid than fabricated memories and were nearly always recalled from a first
      person perspective. In contrast, fabricated differed from true memories in that
      they were judged to be reliably older, were more frequently recalled from a third
      person perspective, and linguistic analysis revealed that they required more
      cognitive effort to generate. No notable differences were found across modality
      of reporting. Finally, it was found that intentionally fabricated memories were
      created by recalling and then "editing" true memories. Overall, these findings
      show that true and fabricated memories systematically differ, despite the fact
      that both are based on true memories.

PMID- 23136888
TI  - Chronic histological damage in early indication biopsies is an independent risk
      factor for late renal allograft failure.
AB  - The impact of early histological lesions of renal allografts on long-term graft
      survival remains unclear. We included all renal allograft recipients transplanted
      at a single center from 1991 to 2001 (N = 1197). All indication biopsies
      performed within the first year after transplantation were rescored according to
      the current Banff classification. Mean follow-up time was 14.8 +/- 2.80 years. In
      multivariate Cox proportional hazards analysis, arteriolar hyalinosis and
      transplant glomerulopathy were independently associated with death-censored graft
      survival, adjusted for baseline demographic covariates. Arteriolar hyalinosis
      correlated with interstitial fibrosis, tubular atrophy, mesangial matrix
      increase, vascular intimal thickening and glomerulosclerosis. Clustering of the
      patients according to these chronic lesions, reflecting the global burden of
      chronic injury, associated better with long-term graft survival than each of the
      chronic lesions separately. Early chronic histological damage was an independent
      risk factor for late graft loss, irrespective whether a specific, progressive
      disease was diagnosed or not, while T cell-mediated rejection did not. We
      conclude that individual chronic lesions like arteriolar hyalinosis, tubular
      atrophy, interstitial fibrosis, glomerulosclerosis, mesangial matrix increase and
      vascular intimal thickening cannot be seen as individual entities. The global
      burden of early chronic histological damage within the first year after
      transplantation importantly affects the fate of the allografts.

PMID- 23136889
TI  - Combined theoretical and experimental investigation of the photodecarboxylation
      of nitrophenylacetates and its implications for the design of improved ortho
      nitrobenzylic caging groups.
AB  - The photodecarboxylation mechanism of different structural isomers of
      nitrophenylacetate (NPA) has been investigated using quantum chemical
      calculations as well as time-resolved UV-pump VIS-probe spectroscopy. It is shown
      that for a proper theoretical description of the excited states of anionic NPA in
      aqueous solution a careful consideration of the influence of the solvent is
      indispensable. In this sense, NPA is an example that demonstrates how character
      and lifetime of the involved excited states affect the results of equilibrium and
      nonequilibrium solvation approaches. An ultrafast decay channel via a repulsive
      singlet state has been found to be responsible for observed ultrafast CO(2)
      release, while another very efficient but slower CO(2) release channel is found
      to proceed via intersystem crossing and subsequent decay via a repulsive triplet
      state. After all, differences and similarities in the observed excited state
      dynamics of the isomers are conclusively explained. Most notably, the much
      smaller quantum yield of CO(2) release from the ortho-isomer is due to an
      alternative excited-state hydrogen-transfer channel, which occurs along a triplet
      and singlet pathway. On the basis of theoretical and experimental evidence
      suggesting that the multiplicity of the route taken determines the photoproduct
      yield, we provide guidelines for the design of ortho-nitrobenzylic caging groups
      with improved uncaging yield.

PMID- 23136890
TI  - General practice-based clinical trials in Germany - a problem analysis.
AB  - BACKGROUND: In Germany, clinical trials and comparative effectiveness studies in
      primary care are still very rare, while their usefulness has been recognised in
      many other countries. A network of researchers from German academic general
      practice has explored the reasons for this discrepancy. METHODS: Based on a
      comprehensive literature review and expert group discussions, problem analyses as
      well as structural and procedural prerequisites for a better implementation of
      clinical trials in German primary care are presented. RESULTS: In Germany, basic
      biomedical science and technology is more reputed than clinical or health
      services research. Clinical trials are funded by industry or a single national
      programme, which is highly competitive, specialist-dominated, exclusive of pilot
      studies, and usually favours innovation rather than comparative effectiveness
      studies. Academic general practice is still not fully implemented, and existing
      departments are small. Most general practitioners (GPs) work in a market-based,
      competitive setting of small private practices, with a high case load. They have
      no protected time or funding for research, and mostly no research training or
      experience. Good Clinical Practice (GCP) training is compulsory for participation
      in clinical trials. The group defined three work packages to be addressed
      regarding clinical trials in German general practice: (1) problem analysis, and
      definition of (2) structural prerequisites and (3) procedural prerequisites.
      Structural prerequisites comprise specific support facilities for general
      practice-based research networks that could provide practices with a point of
      contact. Procedural prerequisites consist, for example, of a summary of specific
      relevant key measures, for example on a web platform. The platform should contain
      standard operating procedures (SOPs), templates, checklists and other supporting
      materials for researchers. CONCLUSION: All in all, our problem analyses revealed
      that a substantial number of barriers contribute to the low implementation of
      clinical research in German general practice. Some issues are deeply rooted in
      Germany's market-based healthcare and academic systems and traditions. However,
      new developments may facilitate change: recent developments in the German
      research landscape are encouraging.

PMID- 23136891
TI  - Effects of homoeologous wheat starch synthase IIa genes on starch properties.
AB  - Near-isogenic lines (NILs) of the eight haplotypes of starch synthase IIa (SSIIa)
      were used to analyze the effects of SSIIa gene dosage on branch chain length,
      gelatinization, pasting, retrogradation, and enzymatic hydrolysis of starches.
      Compared to wild-type, the amylopectin of lines missing one or more active SSIIa
      enzymes had increases in the proportion of short branch chains (DP6-10) and
      decreases in midlength chains (DP11-24), and the size of these differences
      depended on the dosage of active SSIIa enzymes. Of the three loci, SSIIa-A1 had
      the smallest contribution to amylopectin structure and SSIIa-B1 the largest. The
      different effects of the three SSIIa enzymes on starch properties were also seen
      in gelatinization, retrogradation, pasting, and enzymatic hydrolysis properties.
      Such differences in starch properties might be useful in influencing the texture
      and shelf life of food products.

PMID- 23136892
TI  - Differences in cognitive control in children and adolescents with combined and
      inattentive subtypes of ADHD.
AB  - The aim of the present study was to investigate the ability of children with
      attention deficit/hyperactivity disorder-combined subtype (ADHD-C) and
      predominantly inattentive subtype (ADHD-PI) to direct their attention and to
      exert cognitive control in a forced attention dichotic listening (DL) task.
      Twenty-nine, medication-naive participants with ADHD-C, 42 with ADHD-PI, and 40
      matched healthy controls (HC) between 9 and 16 years were assessed. In the DL
      task, two different auditory stimuli (syllables) are presented simultaneously,
      one in each ear. The participants are asked to report the syllable they hear on
      each trial with no instruction on focus of attention or to explicitly focus
      attention and to report either the right- or left-ear syllable. The DL procedure
      is presumed to reflect different cognitive processes: perception (nonforced
      condition/NF), attention (forced-right condition/FR), and cognitive control
      (forced-left condition/FL). As expected, all three groups had normal perception
      and attention. The children and adolescents with ADHD-PI showed a significant
      right-ear advantage also during the FL condition, while the children and
      adolescents in the ADHD-C group showed a no-ear advantage and the HC showed a
      significant left-ear advantage in the FL condition. This suggests that the ADHD
      subtypes differ in degree of cognitive control impairment. Our results may have
      implications for further conceptualization, diagnostics, and treatment of ADHD
      subtypes. 

PMID- 23136893
TI  - Performance of elastography for the evaluation of thyroid nodules: a prospective
      study.
AB  - BACKGROUND: In the ultrasound evaluation of masses, elastography measures
      stiffness, which may predict malignancy. Studies of small or selected subgroups
      suggest that elastography may be useful in the evaluation of thyroid nodules
      (TNs). We prospectively tested the hypothesis that TN stiffness, as measured by
      strain elastography (SE), is an independent predictor of thyroid cancer (TC) in
      unselected TNs. METHODS: In 706 unselected patients with 912 TNs meeting the ATA
      criteria for a fine-needle aspiration biopsy (FNAB), we first performed
      conventional thyroid ultrasound and SE. Nodule stiffness was graded from least to
      most stiff by an elastography score (ES) of ES 0 to ES 3. Surgical resection was
      recommended for FNAB results that were not clearly benign. Bivariate and
      multivariate regression analyses identified the independent predictors of TC.
      RESULTS: There were 86 malignant TNs. ES was a significant predictor of TC
      (p=0.0001). The prevalence of TC was 57 of the 158 TNs (36.1%) for the ES 3
      group, 12 of the 158 TNs (7.7%) for the ES 2 group, 16 of the 565 TNs (2.8%) for
      the ES 1 group, and 1 of the 33 TNs (3%) for the ES 0 group. By multivariate
      regression analysis, the independent predictors of TC were ES,
      microcalcifications, hypoechogenicity, and isthmus location. The positive
      predictive value (PPV) of ES was 36.1%, which was similar to the PPV of
      microcalcifications (35.9%), but greater compared with hypoechogenicity (13.6%)
      and isthmus location (16.9%). The negative predictive value (NPV) of ES was
      97.2%, which was better than any other predictor for malignancy. CONCLUSIONS: We
      conclude that TN stiffness measured by elastography is an independent predictor
      of TC with a PPV that is equal to or greater than that of conventional
      ultrasonographic characteristics. NPV was greater than any other predictor of
      malignancy.

PMID- 23136894
TI  - High or low correlation between co-occuring gene clusters and 16S rRNA gene
      phylogeny.
AB  - Ribosomal RNA (rRNA) genes are universal for all living organisms. Yet, the
      correspondence between genome composition and rRNA phylogeny remains poorly
      known. The aim of this study was to use the information from genome sequence
      databases to address the correlation between rRNA gene phylogeny and total gene
      composition in bacteria. This was done by analysing 327 genomes with TIGRFAM
      functional gene annotations. Our approach consisted of two steps. First, we
      searched for discriminatory clusters of co-occurring genes. Using a multivariate
      statistical approach, we identified 11 such clusters which contain genes that
      were co-occurring only in a subset of genomes and contributed to explain the gene
      content differences between genome subsets. Second, we mapped the discovered
      clusters to 16S rRNA-based phylogeny and calculated the correlation between co
      occuring genes and phylogeny. Six of the 11 clusters exhibited significant
      correlation with 16S rRNA gene phylogeny. The most distinct phylogenetic finding
      was a high correlation between iron-sulfur oxidoreductases in combination with
      carbon nitrogen ligases and Chlorobium. The other correlations identified covered
      relatively large phylogroups: Actinobacteria were positively associated with
      kinases, while Gammaproteobacteria were positively associated with methylases and
      acyltransferases. The suggested functional differences between higher
      phylogroups, however, need experimental verification.

PMID- 23136895
TI  - Allergic rhinitis and its associated co-morbidities at Bugando Medical Centre in
      Northwestern Tanzania; A prospective review of 190 cases.
AB  - BACKGROUND: Allergic rhinitis is one of the commonest atopic diseases which
      contribute to significant morbidity world wide while its epidemiology in Tanzania
      remains sparse. There was paucity of information regarding allergic rhinitis in
      our setting; therefore it was important to conduct this study to describe our
      experience on allergic rhinitis, associated co-morbidities and treatment outcome
      in patients attending Bugando Medical Centre. METHODS: This was descriptive cross
      sectional study involving all patients with a clinical diagnosis of allergic
      rhinitis at Bugando Medical Centre over a three-month period between June 2011
      and August 2011. Data was collected using a pre-tested coded questionnaire and
      analyzed using SPSS statistical computer software version 17.0. RESULTS: A total
      of 190 patients were studied giving the prevalence of allergic rhinitis 14.7%.
      The median age of the patients was 8.5 years. The male to female ratio was 1:1.
      Adenoid hypertrophy, tonsillitis, hypertrophy of inferior turbinate, nasal
      polyps, otitis media and sinusitis were the most common co-morbidities affecting
      92.6% of cases and were the major reason for attending hospital services. Sleep
      disturbance was common in children with adenoids hypertrophy (chi2 = 28.691, P =
      0.000). Allergic conjunctivitis was found in 51.9%. The most common identified
      triggers were dust, strong perfume odors and cold weather (P < 0.05). Strong
      perfume odors affect female than males (chi2 = 4.583, P = 0.032). In this study
      family history of allergic rhinitis was not a significant risk factor  (P
      =0.423). The majority of patients (68.8%) were treated surgically for allergic
      rhinitis co morbidities. Post operative complication and mortality rates were
      2.9% and 1.6% respectively. The overall median duration of hospital stay of in
      patients was 3 days (2 - 28 days). Most patients (98.4%) had satisfactory results
      at discharge. CONCLUSION: The study shows that allergic rhinitis is common in our
      settings representing 14.7% of all otorhinolaryngology and commonly affecting
      children and adolescent. Sufferers seek medical services due to co-morbidities of
      which combination of surgical and medical treatment was needed. High index of
      suspicions in diagnosing allergic rhinitis and early treatment is recommended.

PMID- 23136896
TI  - Integrating frugivory and animal movement: a review of the evidence and
      implications for scaling seed dispersal.
AB  - General principles about the consequences of seed dispersal by animals for the
      structure and dynamics of plant populations and communities remain elusive. This
      is in part because seed deposition patterns emerge from interactions between
      frugivore behaviour and the distribution of food resources, both of which can
      vary over space and time. Here we advocate a frugivore-centred, process-based,
      synthetic approach to seed dispersal research that integrates seed dispersal
      ecology and animal movement across multiple spatio-temporal scales. To guide this
      synthesis, we survey existing literature using paradigms from seed dispersal and
      animal movement. Specifically, studies are discussed with respect to five
      criteria: selection of focal organisms (animal or plant); measurement of animal
      movement; characterization of seed shadow; animal, plant and environmental
      factors included in the study; and scales of the study. Most studies focused on
      either frugivores or plants and characterized seed shadows directly by combining
      gut retention time with animal movement data or indirectly by conducting
      maternity analysis of seeds. Although organismal traits and environmental factors
      were often measured, they were seldom used to characterize seed shadows. Multi
      scale analyses were rare, with seed shadows mostly characterized at fine spatial
      scales, over single fruiting seasons, and for individual dispersers. Novel animal
      and seed-tracking technologies, remote environmental monitoring tools, and
      advances in analytical methods can enable effective implementation of a
      hierarchical mechanistic approach to the study of seed dispersal. This kind of
      mechanistic approach will provide novel insights regarding the complex interplay
      between the factors that modulate animal behaviour and subsequently influence
      seed dispersal patterns across spatial and temporal scales.

PMID- 23136897
TI  - 16th IHIW: a website for antibody-defined HLA epitope Registry.
AB  - The concept that HLA antibodies are specific for epitopes rather than HLA
      antigens is important not only for the determination of mismatch acceptability
      for sensitized patients but also for a better understanding of the antibody
      response to an HLA mismatch. Numerous publications describe epitope-specific
      antibodies, but there is no standardized information about the repertoire of
      clinically relevant HLA epitopes. Under auspices of the 16th IHIW, we have
      developed a website-based registry of antibody-verified HLA epitopes. Epitope
      notations are based on HLA molecular modelling of amino acid residues in
      polymorphic sequence positions. Informative epitope-specific antibodies had been
      induced by a transplant, transfusion or pregnancy and were monoclonal antibodies
      or eluates of sera absorbed with single HLA alleles. Antibody reactivity was
      determined in binding assays with single-allele panels. Antibody
      producer/immunizer HLA types enhanced the characterization of specific epitopes.
      The Registry also includes epitopes described in original research publications.
      Based on the extent of antibody reactivity information, we assigned epitope
      status as confirmed (well documented) or provisional (more data are needed). At
      present, the Registry has 69 HLA-ABC, 53 DRB1/3/4/5, 17 DQ, 8 DP and 22 MICA
      antibody-verified epitopes and will be updated on a quarterly basis. Laboratories
      worldwide continue to submit data about previously unreported antibody-specific
      epitopes. For each epitope, the website shows its amino acid composition and HLA
      alleles that share the epitope. Links show antibody reactivity patterns,
      sensitization information and references. Other links show molecular modelling of
      corresponding structural epitopes and polymorphic residue information for epitope
      carrying alleles. The website will also have a link to epitope frequency
      information in different populations. Search functions will list mismatched
      epitopes on mismatched alleles for selected HLA types. The HLA Epitope Registry
      will become a valuable resource for researchers interested in HLA compatibility
      at the epitope level and investigating antibody responses to HLA mismatches.

PMID- 23136898
TI  - A theoretical investigation of two typical two-photon pH fluorescent probes.
AB  - Intracellular pH plays an important role in many cellular events, such as cell
      growth, endocytosis, cell adhesion and so on. Some pH fluorescent probes have
      been reported, but most of them are one-photon fluorescent probes, studies about
      two-photon fluorescent probes are very rare. In this work, the geometrical
      structure, electronic structure and one-photon properties of a series of two
      photon pH fluorescent probes have been theoretically studied by using density
      functional theory (DFT) method. Their two-photon absorption (TPA) properties are
      calculated using the method of ZINDO/sum-over-states method. Two types of two
      photon pH fluorescent probes have been investigated by theoretical methods. The
      mechanisms of the Photoinduced Charge Transfer (PCT) probes and the Photoinduced
      Electron Transfer (PET) probes are verified specifically. Some designed
      strategies of good two-photon pH fluorescent probes are suggested on the basis of
      the investigated results of two mechanisms. For the PCT probes, substituting a
      stronger electron-donating group for the terminal methoxyl group is an advisable
      choice to increase the TPA cross section. For the PET probes, the TPA cross
      sections increase upon protonation.

PMID- 23136900
TI  - Decreased risk of melanoma and nonmelanoma skin cancer in patients with vitiligo:
      a survey among 1307 patients and their partners.
AB  - BACKGROUND: Vitiligo is a common skin disease characterized by autoimmune
      melanocyte destruction. Recent genetic studies suggest a lower susceptibility to
      melanoma in patients with vitiligo; however, lifetime melanoma prevalence in
      patients with vitiligo has not previously been studied. Nonmelanoma skin cancer
      (NMSC) prevalence has been studied, but only in small studies and with
      contradictory results. OBJECTIVES: This retrospective, comparative cohort survey
      was designed to assess lifetime prevalences of melanoma and NMSC in patients with
      vitiligo compared with nonvitiligo controls. METHODS: Patients with nonsegmental
      vitiligo, who visited our clinic between January 1995 and September 2010, and
      were aged 50 years or older at the time of the study, were invited to participate
      in a postal survey. The questions regarded demographics, vitiligo
      characteristics, phototherapy history, skin cancer risk factors and the number of
      skin cancers experienced during the patient's lifetime. Patients were asked to
      have their partner fill in a control questionnaire. All skin cancers were
      validated by a pathology report. In total 2635 invitations were sent and 1307
      eligible questionnaires were returned (50%). Multivariate logistic regression
      models were used to quantify adjusted odds ratios (ORs) and 95% confidence
      intervals (CIs) for associations between vitiligo and lifetime prevalences of
      melanoma and NMSC. RESULTS:  Adjusted for confounders, patients with vitiligo had
      a threefold lower probability of developing melanoma (adjusted OR 0.32; 95% CI
      0.12-0.88) and NMSC (adjusted OR 0.28; 95% CI 0.16-0.50). Subgroup analyses of
      patients treated with narrowband ultraviolet (UV) B, and psoralen and UVA did not
      show dose-related trends of increased age-adjusted lifetime prevalence of
      melanoma or NMSC. CONCLUSIONS: Our findings suggest that patients with vitiligo
      have a decreased risk of both melanoma and NMSC.

PMID- 23136902
TI  - Structural and electronic comparison of 1st row transition metal complexes of a
      tripodal iminopyridine ligand.
AB  - We report the preparation and characterization of a series of divalent 3d
      transition metal complexes (Cr to Zn, 1-7), featuring the multidentate, tripodal
      iminopyridine Schiff-base ligand trimethyl 6,6',6"-((1E,1'E,1"E)
      ((nitrilotris(ethane-2,1-diyl))tris(azanylylidene))tris
      (methanylylidene))trinicotinate (L(5-OOMe)). X-ray structural studies carried out
      on 1-5 and 7 reveal complex geometries ranging from local octahedral coordination
      to significant distortion toward trigonal prismatic geometry to heptacoordinate
      environments. Regardless of coordination mode, magnetic and spectroscopic studies
      show the ligand to provide moderately strong ligand fields: the Fe complex is low
      spin, while the Co and Mn complexes are high-spin at all temperatures probed.
      Cyclic voltammograms exhibit multiple reversible ligand-based reductions, which
      are relatively consistent throughout the series; however, the electrochemical
      behavior of the Cr complex 1 is fundamentally different from those of the other
      complexes. Time-dependent (TD) density functional theory (DFT) and natural
      transition orbital (NTO) computational analyses are presented for the ligand, its
      anion, and complexes 1-7: the computed spectra reproduce the major differential
      features of the observed visible absorption spectra, and NTOs provide viable
      interpretations for the observed features. The combined studies indicate that all
      complexes contain neutral ligands bound to M(II) ions, except for the Cr complex
      1, which is best described as a Cr(III) species bound to a radical anionic
      ligand. 

PMID- 23136901
TI  - Preliminary evidence for a gene-environment interaction in predicting alcohol use
      disorders in adolescents.
AB  - BACKGROUND: Emerging research suggests that genetic influences on adolescent
      drinking are moderated by environmental factors. The present study builds on
      molecular-genetic findings by conducting the first analysis of gene-environment
      interactions in the association between a functional single nucleotide
      polymorphism (SNP) of the MU-opioid receptor (OPRM1) gene (A118G) and risk of
      developing an alcohol use disorder (AUD) during adolescence. Specifically, we
      tested whether variation in parenting practices or affiliation with deviant peers
      moderated the link between the OPRM1 gene and risk of an AUD. METHODS:
      Adolescents reporting European ancestry (N = 104), ages 12 to 19 years (M =
      15.60, SD = 1.77), were interviewed to ascertain AUD diagnoses, provided a DNA
      sample for genetic analyses, and completed measures of parental monitoring and
      deviant peer affiliation. Logistic regression was used to test the effects of
      environmental variables and their interactions with OPRM1 genotype as predictors
      of AUD diagnosis while controlling for age and sex. RESULTS: Case-control
      comparisons showed that the proportion of youth with an AUD (n = 18)
      significantly differed by genotype such that 33.3% of G allele carriers met
      criteria for an AUD compared to 10.8% of youth who were homozygous for the A
      allele (p = 0.006). The OPRM1 * parental monitoring (odds ratio = 0.16) and OPRM1
      * deviant peer affiliation (odds ratio = 7.64) interactions were significant
      predictors of AUD risk, such that G allele carriers with high levels of deviant
      peer affiliation or lower levels of parental monitoring had the greatest
      likelihood of developing an AUD (p-values <0.01). CONCLUSIONS: This study
      provides initial evidence that the association between the A118G SNP of the OPRM1
      gene and risk of AUDs is moderated by modifiable factors. These results are
      limited, however, by the small sample size and require replication.

PMID- 23136903
TI  - Permissive hypofiltration: an alternative view.
AB  - If permissive hypercapnia is used in the context of protective ventilation for
      patients with acute respiratory distress syndrome, it must be highlighted that
      the alveoli in these patients are still exposed to significant stress. Similarly,
      early renal replacement therapy is not necessarily a protective therapy for acute
      kidney injury and loop diuretics are not necessarily harmful. It is conceivable
      that early initiation of 'protective' low-dose (10 ml/kg/h) continuous renal
      replacement therapy with zero balanced ultrafiltration in association with
      administration of (high dose) diuretics may help to rest the kidneys while
      ensuring preservation of urine output. 

PMID- 23136904
TI  - 30-day in-hospital mortality after acute myocardial infarction in Tuscany
      (Italy): an observational study using hospital discharge data.
AB  - BACKGROUND: Coronary heart disease is the leading cause of mortality in the
      world. One of the outcome indicators recently used to measure hospital
      performance is 30-day mortality after acute myocardial infarction (AMI). This
      indicator has proven to be a valid and reproducible indicator of the
      appropriateness and effectiveness of the diagnostic and therapeutic process for
      AMI patients after hospital admission. The aim of this study was to examine the
      determinants of inter-hospital variability on 30-day in-hospital mortality after
      AMI in Tuscany. This indicator is a proxy of 30-day mortality that includes only
      deaths occurred during the index or subsequent hospitalizations. METHODS: The
      study population was identified from hospital discharge records (HDRs) and
      included all patients with primary or secondary ICD-9-CM codes of AMI (ICD-9
      codes 410.xx) that were discharged between January 1, 2009 and November 30, 2009
      from any hospital in Tuscany. The outcome of interest was 30-day all-cause in
      hospital mortality, defined as a death occurring for any reason in the hospital
      within 30 days of the admission date. Because of the hierarchical structure of
      the data, with patients clustered into hospitals, random-effects (multilevel)
      logistic regression models were used. The models included patient risk factors
      and random intercepts for each hospital. RESULTS: The study included 5,832
      patients, 61.90% male, with a mean age of 72.38 years. During the study period,
      7.99% of patients died within 30 days of admission. The 30-day in-hospital
      mortality rate was significantly higher among patients with ST segment elevation
      myocardial infarction (STEMI) compared with those with non-ST segment elevation
      myocardial infarction (NSTEMI). The multilevel analysis which included only the
      hospital variance showed a significant inter-hospital variation in 30-day in
      hospital mortality. When patient characteristics were added to the model, the
      hospital variance decreased. The multilevel analysis was then carried out
      separately in the two strata of patients with STEMI and NSTEMI. In the STEMI
      group, after adjusting for patient characteristics, some residual inter-hospital
      variation was found, and was related to the presence of a cardiac catheterisation
      laboratory. CONCLUSION: We have shown that it is possible to use routinely
      collected administrative data to predict mortality risk and to highlight inter
      hospital differences. The distinction between STEMI and NSTEMI proved to be
      useful to detect organisational characteristics, which affected only the STEMI
      subgroup.

PMID- 23136905
TI  - Segmental disinhibition suppresses C-fiber inputs to the rat superficial
      medullary dorsal horn via the activation of GABAB receptors.
AB  - Specialized primary afferents, although they terminate in different laminae
      within the dorsal horn (DH), are known to interact through local circuit
      excitatory and inhibitory neurons. That a loss of segmental inhibition probably
      contributes to persistent pain hypersensitivity during chronic pain raises the
      question as to how disinhibition-induced changes in cross-modal interactions
      account for chronic pain symptoms. We sought to characterize how pharmacological
      blockade of glycine and gamma-aminobutyric acid (GABA) receptors modifies
      synaptic transmission between primary afferent fibers and second-order neurons by
      recording field potentials in the superficial medullary dorsal horn (MDH) of
      anesthetized rats. Transcutaneous electrical stimulation evokes three negative
      field potentials elicited by, from earliest to latest, Abeta-, Adelta- and C
      fiber primary afferents. Blocking segmental glycine and/or GABA(A)  receptors,
      with strychnine and bicuculline, respectively, strongly facilitates Abeta- and
      Adelta-fiber-evoked polysynaptic field potentials but, conversely, inhibits, or
      even abolishes, the whole C-fiber field potential. Blocking segmental GABA(B) 
      receptors, with phaclofen, reverses such suppression of C-fiber field potentials.
      Interestingly, it also potentiates C-fiber field potentials under control
      conditions. Finally, activation of segmental GABA(B)  receptors, with baclofen,
      preferentially inhibits C-fiber field potentials. Our results suggest that
      activation of A-fiber primary afferents inhibits C-fiber inputs to the MDH by the
      way of polysynaptic excitatory pathways, last-order GABAergic interneurons and
      presynaptic GABA(B)  receptors on C-fiber primary afferents. Under physiological
      conditions, activation of such local DH circuits is closely controlled by
      segmental inhibition but it might contribute to paradoxically reduced pain
      hypersensitivity under pathological disinhibition.

PMID- 23136906
TI  - PKC-mediated USP phosphorylation at Ser35 modulates 20-hydroxyecdysone signaling
      in Drosophila.
AB  - The nuclear receptor complex of the steroid hormone, 20-hydroxyecdysone (20E), is
      a heterodimer composed of EcR and USP. Our previous studies in Drosophila suggest
      that PKC modulates 20E signaling by phosphorylating EcR-USP. However, the exact
      phosphorylation sites in EcR and USP have not been identified. Using LC-MS/MS
      analysis, we first identified Ser35 of USP as a PKC phosphorylation site.
      Mutation of USP Ser35 to Ala35 in S2 cells not only eliminated USP
      phosphorylation, but also attenuated the 20E-induced luciferase activity,
      mimicking the treatment with a PKC-specific inhibitor chelerythrine chloride in
      Kc cells. In the larval salivary glands (SG), inhibition of PKC activity with the
      binary GAL4/UAS system reduced USP phosphorylation and down-regulated the 20E
      primary-response genes, E75B and Br-C, and RNAi knockdown of Rack1 had stronger
      inhibitory effects than overexpression of PKCi. Moreover, RNAi knockdown of four
      PKC isozyme genes expressed in the SG exhibited a variety of inhibitory effects
      on USP phosphorylation and expression of E75B and Br-C, with the strongest
      inhibitory effects occurring when aPKC was knocked down by RNAi. Taken together,
      we conclude that PKC-mediated USP phosphorylation at Ser35 modulates 20E
      signaling in Drosophila.

PMID- 23136907
TI  - Physical capacity and psychological mood in association with self-reported work
      ability in vibration-exposed patients with hand symptoms.
AB  - BACKGROUND: The aim of this study was to investigate whether self-reports of
      work ability correlated to the results of quantitative tests measuring physical
      capacity and a questionnaire assessing psychological mood in vibration-exposed
      patients with hand symptoms. METHODS: The participants comprised 47 patients (36
      men and eleven women) with exposure to hand vibration and vascular and/or
      neurological symptoms in the hands. They performed several quantitative tests
      (manual dexterity, hand grip strength, finger strength) and completed the Work
      Ability Index (WAI) and Hospital Anxiety and Depression Scale (HADS)
      questionnaires. RESULTS: Correlation analysis revealed statistically significant
      associations between the WAI results, the HADS indices, hand grip and finger
      strength, and manual dexterity measured using the Purdue Pegboard(r). Multiple
      regression analysis revealed age and HADS indices as the strongest predictors of
      work ability. CONCLUSIONS: The patient's age and psychological mood may be
      stronger predictors of work ability compared with results from tests measuring
      physical capacity of the hands in vibration-exposed patients with hand symptoms.
      When using the WAI as an instrument for assessing work ability in these patients,
      health care providers need to be more aware of the impact of the psychological
      mood.

PMID- 23136908
TI  - Salivary and lacrimal gland dysfunction after remnant ablation with radioactive
      iodine in patients with differentiated thyroid carcinoma prepared with
      recombinant human thyrotropin.
AB  - BACKGROUND: One of the adverse effects of radioactive iodine (131I) treatment in
      patients with thyroid cancer is damage to the salivary and lacrimal glands. In
      almost all studies evaluating salivary and lacrimal gland dysfunction, the
      patients received 131I after levothyroxine (L-T4) withdrawal. Since the
      biokinetics of 131I after recombinant human thyrotropin (rhTSH) is not the same
      as in hypothyroidism, studies need to evaluate 131I-induced salivary and lacrimal
      toxicity after preparation with rhTSH. This prospective study investigated the
      occurrence of salivary and lacrimal damage after ablation with 131I using this
      preparation. METHODS: One hundred forty-eight patients who had a total
      thyroidectomy were included in the study. The subjects were evaluated after
      thyroidectomy during L-T4 use to exclude those who already showed symptoms or had
      a history of ocular or oral disease. Symptoms were investigated 12 and 18 months
      after ablation. In patients who had persistent symptoms, specific tests were
      performed to confirm glandular dysfunction and to rule out other causes. RESULTS:
      Twelve months after ablation, symptoms of salivary or lacrimal dysfunction were
      observed in 10 (6.7%) patients, including oral symptoms in 8 (5.4%) and ocular
      symptoms in 6 (4%). Eighteen months after 131I, symptoms persisted in eight
      (5.4%) patients, including oral symptoms in seven (4.7%) and ocular symptoms in
      five (3.4%). In all of the patients, glandular dysfunction was confirmed by
      specific tests and other causes were ruled out. No symptoms were seen in the
      patients who received a low 131I dose (30 mCi). In the patients who received high
      131I doses (100 or 150 mCi), symptoms were noted 12 months after 131I in 10
      patients (9.2%), and 18 months after 131I in 8 patients (7.4%). CONCLUSIONS:
      Apparently, the rates of salivary and lacrimal damage were lower than those
      reported in prospective studies that used similar 131I activities, but these
      studies were performed in patients who were hypothyroid at the time of 131I
      ablation. Further studies are needed to compare radiotoxicity between patients
      prepared for 131I ablation with rhTSH and those prepared for 131I ablation with L
      T4 withdrawal.

PMID- 23136910
TI  - Malaria vaccine trials--beyond efficacy end points.

PMID- 23136911
TI  - Meta-analysis: efficacy of small bowel preparation for small bowel video capsule
      endoscopy.
AB  - OBJECTIVE: It is unclear whether small bowel visibility in video capsule
      endoscopy (VCE) is enhanced by the use of bowel preparation in addition to pre
      procedural fasting. The objective of this study was to clarify this issue by
      means of a systematic review of the literature and meta-analysis. METHODS:
      Randomised controlled trials comparing the use of laxative bowel preparation with
      fasting alone were identified using a literature search. Categorical measures of
      treatment efficacy were extracted from qualifying studies and pooled using random
      effects meta-analyses. Primary analysis compared any bowel preparation with
      fasting alone; subsidiary analyses assessed diagnostic yield and results for each
      regimen. RESULTS: Eight studies were identified, using either polyethylene glycol
      (PEG) or sodium phosphate (NaP) based regimens. No qualifying studies were
      identified using other laxatives. Study quality was sufficiently high to warrant
      meta-analysis. Use of any form of bowel preparation yielded significantly better
      visibility than fasting alone (OR = 2.31; 95% CI = 1.46-3.63; p < 0.0001).
      Similar results were seen for diagnostic yield (OR = 1.88; 95% CI = 1.24-2.84; p
      = 0.023). When sub-analysed according to the treatment used, PEG-based regimens
      showed benefit (OR = 3.11; 95% CI = 1.96-4.94; p < 0.0001), while NaP-based
      regimens yielded no significant difference from fasting alone (OR = 1.32; 95% CI
      = 0.59-2.96; p < 0.0001). LIMITATIONS: The study did not consider results from
      retrospective studies, nor those which did not give a categorical measure of
      efficacy. The impact of prokinetic and other adjunctive treatments was not
      considered. The results are only relevant to the most commonly used video
      capsule, as data for newer alternative devices have not yet been published.
      CONCLUSION: Based on the results of this analysis, the use of bowel preparation
      alongside fasting is recommended for VCE. PEG-based regimens offer a clear
      advantage in these patients, while the currently available evidence base does not
      support the use of NaP. For VCE, lower volume PEG appears to be as efficacious as
      higher volumes traditionally used for colonoscopy preparation.

PMID- 23136909
TI  - A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants.
AB  - BACKGROUND: The candidate malaria vaccine RTS,S/AS01 reduced episodes of both
      clinical and severe malaria in children 5 to 17 months of age by approximately
      50% in an ongoing phase 3 trial. We studied infants 6 to 12 weeks of age
      recruited for the same trial. METHODS: We administered RTS,S/AS01 or a comparator
      vaccine to 6537 infants who were 6 to 12 weeks of age at the time of the first
      vaccination in conjunction with Expanded Program on Immunization (EPI) vaccines
      in a three-dose monthly schedule. Vaccine efficacy against the first or only
      episode of clinical malaria during the 12 months after vaccination, a coprimary
      end point, was analyzed with the use of Cox regression. Vaccine efficacy against
      all malaria episodes, vaccine efficacy against severe malaria, safety, and
      immunogenicity were also assessed. RESULTS: The incidence of the first or only
      episode of clinical malaria in the intention-to-treat population during the 14
      months after the first dose of vaccine was 0.31 per person-year in the RTS,S/AS01
      group and 0.40 per person-year in the control group, for a vaccine efficacy of
      30.1% (95% confidence interval [CI], 23.6 to 36.1). Vaccine efficacy in the per
      protocol population was 31.3% (97.5% CI, 23.6 to 38.3). Vaccine efficacy against
      severe malaria was 26.0% (95% CI, -7.4 to 48.6) in the intention-to-treat
      population and 36.6% (95% CI, 4.6 to 57.7) in the per-protocol population.
      Serious adverse events occurred with a similar frequency in the two study groups.
      One month after administration of the third dose of RTS,S/AS01, 99.7% of children
      were positive for anti-circumsporozoite antibodies, with a geometric mean titer
      of 209 EU per milliliter (95% CI, 197 to 222). CONCLUSIONS: The RTS,S/AS01
      vaccine coadministered with EPI vaccines provided modest protection against both
      clinical and severe malaria in young infants. (Funded by GlaxoSmithKline
      Biologicals and the PATH Malaria Vaccine Initiative; RTS,S ClinicalTrials.gov
      number, NCT00866619.).

PMID- 23136912
TI  - Future good scientific publishing practice will necessitate wider data
      transparency.

PMID- 23136913
TI  - Update on rifampin, rifabutin, and rifapentine drug interactions.
AB  - BACKGROUND: Rifampin is a potent inducer of both cytochrome P-450 oxidative
      enzymes and the P-glycoprotein transport system. Among numerous well documented,
      clinically significant interactions, examples include warfarin, oral
      contraceptives, itraconazole, digoxin, verapamil, simvastatin, and human
      immunodeficiency virus-related protease inhibitors. Rifabutin reduces serum
      concentrations of antiretroviral agents, but less so than rifampin. Rifapentine
      is also an inducer of drug metabolism. METHODS: A literature search of English
      language journals from 2008 to March 2012 was completed using several databases,
      including PubMed, EMBASE, and SCOPUS. Search terms included rifampin, rifabutin,
      rifapentine AND drug interactions. FINDINGS: Examples of clinically relevant
      interactions with rifampin demonstrated by recent reports include posaconazole,
      voriconazole, oxycodone, risperidone, mirodenafil, and ebastine. CONCLUSIONS: To
      avoid a reduced therapeutic response, therapeutic failure, or toxic reactions
      when rifampin, rifabutin, or rifapentine are added to or discontinued from
      medication regimens, clinicians need to be aware of these interactions. Recent
      studies have indicated that other transporter systems play a role in these drug
      interactions. As reports of rifampin drug interactions continue to grow, this
      review is a reminder to clinicians to be vigilant.

PMID- 23136914
TI  - Family-based models for childhood-obesity intervention: a systematic review of
      randomized controlled trials.
AB  - Effective interventions are needed to address the growing epidemic of childhood
      obesity. In the past 35 years, family-based approach has gradually developed as a
      preferred intervention. This review aimed to examine the methodological rigour
      and treatment effectiveness of family-based interventions according to
      intervention types and theoretical orientations. A total of 15 randomized
      controlled trials (RCTs) of family-based lifestyle interventions for children and
      adolescents aged 2-19 years were included. The adapted Methodological Quality
      Rating Scales (MQRS) and a four-grade qualitative scoring scheme were adopted to
      evaluate the methodological rigour and the effectiveness of treatment,
      respectively. The average MQRS score was 7.93 out of 14 points. Ten of the 15
      RCTs had well aligned their research questions with appropriate research methods.
      The overall short-term outcome of the15 RCTs were satisfactory with an average
      score of 3.1. Family-based interventions rooted in behaviour theory achieved
      better results than those theoretically connected to family systems theory in
      terms of treatment effectiveness. Results suggest future studies to improve the
      methodological design and continue to explore the potential of the family systems
      approach. 

PMID- 23136916
TI  - Origin of regioselectivity in the reactions of nitronate and enolate ambident
      anions.
AB  - The reactions of nitronates of ring-substituted phenylnitromethanes and enolates
      of ring-substituted 1-phenyl-2-propanones with MeOBs gave exclusively the O
      methylated and C-methylated products, respectively. DFT calculations suggested
      that two factors, namely, intrinsic barriers and metal-cation coordination,
      control the C/O selectivity. The kinetic preference for O-methylation in the
      reactions of nitronates arises from the intrinsic barriers, which are ca. 10
      kcal/mol lower for O-methylation than for C-methylation. The situation is the
      same for the gas-phase reaction of an enolate, in which the O-methylation is more
      favorable than the C-methylation. The experimentally observed C-selectivity of
      enolate reactions in solution is due to the metal-cation coordination, which
      hinders O-methylation for enolates. The effects of the enolate reactivity and the
      solvent on the C/O selectivity are also rationalized to arise from the two
      factors.

PMID- 23136915
TI  - Resistant starch and pullulan reduce postprandial glucose, insulin, and GLP-1,
      but have no effect on satiety in healthy humans.
AB  - The aim of this study was to determine the effects of three novel fibers on
      satiety and serum parameters. In a randomized, double-blind, crossover design,
      fasted subjects (n=20) consumed a low-fiber control breakfast or one of four
      breakfasts containing 25 g of fiber from soluble corn fiber (SCF) or resistant
      starch (RS), alone or in combination with pullulan (SCF+P and RS+P). Visual
      analog scales assessed appetite, and blood samples were collected to measure
      glucose, insulin, ghrelin, and glucagon-like peptide-1 (GLP-1). The fiber
      treatments did not influence satiety or energy intake compared to control. RS+P
      significantly reduced glucose, insulin, and GLP-1, but neither SCF treatment
      differed from control. To conclude, these fibers have little impact on satiety
      when provided as a mixed meal matched for calories and macronutrients. Additional
      research regarding the physiological effects of these novel fibers is needed to
      guide their use as functional ingredients in food products.

PMID- 23136917
TI  - On the taxonomy of optimization problems under estimation of distribution
      algorithms.
AB  - Understanding the relationship between a search algorithm and the space of
      problems is a fundamental issue in the optimization field. In this paper, we lay
      the foundations to elaborate taxonomies of problems under estimation of
      distribution algorithms (EDAs). By using an infinite population model and
      assuming that the selection operator is based on the rank of the solutions, we
      group optimization problems according to the behavior of the EDA. Throughout the
      definition of an equivalence relation between functions it is possible to
      partition the space of problems in equivalence classes in which the algorithm has
      the same behavior. We show that only the probabilistic model is able to generate
      different partitions of the set of possible problems and hence, it predetermines
      the number of different behaviors that the algorithm can exhibit. As a natural
      consequence of our definitions, all the objective functions are in the same
      equivalence class when the algorithm does not impose restrictions to the
      probabilistic model. The taxonomy of problems, which is also valid for finite
      populations, is studied in depth for a simple EDA that considers independence
      among the variables of the problem. We provide the sufficient and necessary
      condition to decide the equivalence between functions and then we develop the
      operators to describe and count the members of a class. In addition, we show the
      intrinsic relation between univariate EDAs and the neighborhood system induced by
      the Hamming distance by proving that all the functions in the same class have the
      same number of local optima and that they are in the same ranking positions.
      Finally, we carry out numerical simulations in order to analyze the different
      behaviors that the algorithm can exhibit for the functions defined over the
      search space [Formula: see text]. 

PMID- 23136918
TI  - Models of performance of evolutionary program induction algorithms based on
      indicators of problem difficulty.
AB  - Modeling the behavior of algorithms is the realm of evolutionary algorithm
      theory. From a practitioner's point of view, theory must provide some guidelines
      regarding which algorithm/parameters to use in order to solve a particular
      problem. Unfortunately, most theoretical models of evolutionary algorithms are
      difficult to apply to realistic situations. However, in recent work (Graff and
      Poli, 2008, 2010), where we developed a method to practically estimate the
      performance of evolutionary program-induction algorithms (EPAs), we started
      addressing this issue. The method was quite general; however, it suffered from
      some limitations: it required the identification of a set of reference problems,
      it required hand picking a distance measure in each particular domain, and the
      resulting models were opaque, typically being linear combinations of 100 features
      or more. In this paper, we propose a significant improvement of this technique
      that overcomes the three limitations of our previous method. We achieve this
      through the use of a novel set of features for assessing problem difficulty for
      EPAs which are very general, essentially based on the notion of finite
      difference. To show the capabilities or our technique and to compare it with our
      previous performance models, we create models for the same two important classes
      of problems-symbolic regression on rational functions and Boolean function
      induction-used in our previous work. We model a variety of EPAs. The comparison
      showed that for the majority of the algorithms and problem classes, the new
      method produced much simpler and more accurate models than before. To further
      illustrate the practicality of the technique and its generality (beyond EPAs), we
      have also used it to predict the performance of both autoregressive models and
      EPAs on the problem of wind speed forecasting, obtaining simpler and more
      accurate models that outperform in all cases our previous performance models.

PMID- 23136919
TI  - Antibacterial activity of long-chain fatty alcohols against mycobacteria.
AB  - Tuberculosis is caused by the bacterium Mycobacterium tuberculosis and results in
      innumerable deaths across the world. The emergence of multidrug-resistant and
      extremely drug-resistant tuberculosis strains and its coinfection with HIV has
      made tuberculosis more difficult to treat. Therefore, new antimycobacterial
      agent(s) for both therapy and disinfection are urgently required. In this context
      the present study describes the antibacterial property of long-chain fatty
      alcohols against mycobacteria. The antimycobacterial activities of alcohols with
      chain length ranging from C(5) to C(13) were examined against Mycobacterium
      smegmatis mc(2) 155 and M. tuberculosis H(37)R(v). The best activity was found
      with one with a C(10) chain length. This bactericidal activity can partly be
      attributed to its ability to damage the robust and complex cell envelope of
      Mycobacteria. Moreover, our study reveals the ability of decanol to attenuate
      biofilm formation by M. smegmatis. This knowledge can be used to develop new
      therapeutics and disinfectants against mycobacteria.

PMID- 23136920
TI  - Psychological testing and treatment implications: we can say more.
AB  - Psychologists invest considerable time and labor in psychological testing and
      report writing. Patients and families expose vulnerabilities and make a
      significant financial and time investment in the hope that testing will make a
      difference in treatment. Frequently, though, handling of treatment implications
      in reports is generic, which might not justify the time, expense, and emotional
      investment involved in the evaluation. As diagnosticians, we have the
      responsibility and potential to contribute more meaningfully to the work of our
      referring colleagues and the treatment of the patients we assess. I review the
      psychotherapy research literature to highlight evidence-based findings that can
      serve as guideposts in formulating treatment implications. Subsequently, I
      illustrate how we can use test data to make nuanced inferences about therapeutic
      alliance, potential resistances, likely transferences and countertransferences,
      and conceptualizing treatment on the supportive-expressive continuum.

PMID- 23136921
TI  - Does expanded criteria donor status modify the outcomes of kidney transplantation
      from donors after cardiac death?
AB  - The outcomes of kidney transplants that simultaneously exhibit donation after
      cardiac death (DCD) and expanded criteria donor (ECD) characteristics have not
      been well studied. We examined the outcomes of DCD versus non-DCD kidney
      transplants as a function of ECD status and the kidney donor risk index (KDRI). A
      cohort study of 67 816 deceased donor kidney transplant recipients (KTR),
      including 562 ECD/DCD KTR, from January 1, 2000 to December 31, 2009 was
      conducted using the Scientific Registry of Transplant Recipients. In a
      multivariable Cox proportional hazards model, the modestly increased risk of
      total graft failure in DCD versus non-DCD KTR was not significantly modified by
      ECD status (hazard ratio1.07 [95% CI: 1.01, 1.15] for non-ECD vs. 1.21 [95% CI:
      1.04, 1.40] for ECD, p for interaction = 0.14).Moreover, the hazard ratios did
      not significantly vary by KDRI quintiles (p = 0.40). Similar trends were seen for
      death-censored graft failure and death with graft function. In conclusion, ECD
      status or higher KDRI score did not appreciably increase the relative hazard of
      adverse graft and patient outcomes in DCD KTR. These findings suggest that the
      judicious use of ECD/DCD donor kidneys may be an appropriate strategy to expand
      the donor pool.

PMID- 23136922
TI  - Large hydrogen-bonded pre-nucleation (HSO4-)(H2SO4)m(H2O)k and (HSO4
      )(NH3)(H2SO4)m(H2O)k clusters in the earth's atmosphere.
AB  - The importance of pre-nucleation cluster stability as the key parameter
      controlling nucleation of atmospheric airborne ions is well-established. In this
      Article, large ternary ionic (HSO(4)(-))(H(2)SO(4))(m)(NH(3))(H(2)O)(n) clusters
      have been studied using Density Functional Theory (DFT) and composite ab initio
      methods. Twenty classes of clusters have been investigated, and thermochemical
      properties of common atmospheric (HSO(4)(-))(H(2)SO(4))(m)(NH(3))(0)(H(2)O)(k)
      and (HSO(4)(-))(H(2)SO(4))(m)(NH(3))(1)(H(2)O)(n) clusters (with m, k, and n up
      to 3) have been obtained. A large amount of new themochemical and structural data
      ready-to-use for constraining kinetic nucleation models has been reported. We
      have performed a comprehensive thermochemical analysis of the obtained data and
      have investigated the impacts of ammonia and negatively charged bisulfate ion on
      stability of binary clusters in some detail. The comparison of theoretical
      predictions and experiments shows that the PW91PW91/6-311++G(3df,3pd) results are
      in very good agreement with both experimental data and high level ab initio
      CCSD(T)/CBS values and suggest that the PW91PW91/6-311++G(3df,3pd) method is a
      viable alternative to higher level ab initio methods in studying large pre
      nucleation clusters, for which the higher level computations are prohibitively
      expensive. The uncertainties in both theory and experiments have been
      investigated, and possible ways of their reduction have been proposed.

PMID- 23136923
TI  - Elucidating molecular iridium water oxidation catalysts using metal-organic
      frameworks: a comprehensive structural, catalytic, spectroscopic, and kinetic
      study.
AB  - As a new class of porous, crystalline, molecular materials, metal-organic
      frameworks (MOFs) have shown great promise as recyclable and reusable single-site
      solid catalysts. Periodic order and site isolation of the catalytic struts in
      MOFs facilitate the studies of their activities and reaction mechanisms. Herein
      we report the construction of two highly stable MOFs (1 and 2) using elongated
      dicarboxylate bridging ligands derived from Cp*Ir(L)Cl complexes (L = dibenzoate
      substituted 2,2'-bipyridine, bpy-dc, or dibenzoate-substituted 2-phenylpyridine,
      ppy-dc) and Zr(6)O(4)(OH)(4)(carboxylate)(12) cuboctahedral secondary building
      units (SBUs) and the elucidation of water oxidation pathways of the Cp*Ir(L)Cl
      catalysts using these MOFs. We carried out detailed kinetic studies of Ce(4+)
      driven water oxidation reactions (WORs) catalyzed by the MOFs using UV-vis
      spectroscopy, phosphorescent oxygen detection, and gas chromatographic analysis.
      These results confirmed not only water oxidation activity of the MOFs but also
      indicated oxidative degradation of the Cp* rings during the WOR. The (bpy
      dc)Ir(H(2)O)(2)XCl (X is likely a formate or acetate group) complex resulted from
      the oxidative degradation process was identified as a competent catalyst
      responsible for the water oxidation activity of 1. Further characterization of
      the MOFs recovered from WORs using X-ray photoelectron, diffuse-reflectance UV
      vis absorption, luminescence, and infrared spectroscopies supported the identity
      of (bpy-dc)Ir(H(2)O)(2)XCl as an active water oxidation catalyst. Kinetics of MOF
      catalyzed WORs were monitored by Ce(4+) consumptions and fitted with a reaction
      diffusion model, revealing an intricate relationship between reaction and
      diffusion rates. Our work underscores the opportunity in using MOFs as well
      defined single-site solid catalytic systems to reveal mechanistic details that
      are difficult to obtain for their homogeneous counterparts.

PMID- 23136924
TI  - Resistance of human butyrylcholinesterase to methylene blue-catalyzed
      photoinactivation; mass spectrometry analysis of oxidation products.
AB  - Methylene blue, 3, 7-bis(dimethylamino)-phenothiazin-5-ium chloride, is a
      reversible inhibitor of human butyrylcholinesterase (BChE) in the absence of
      light. In the presence of light and oxygen, methylene blue promotes irreversible
      inhibition of human BChE as a function of time, requiring 3 h irradiation to
      inhibit 95% activity. Inactivation was accompanied by a progressive loss of
      Coomassie-stained protein bands on native and denaturing polyacrylamide gels,
      suggesting backbone fragmentation. Aggregation was not detected. MALDI-TOF/TOF
      mass spectrometry identified oxidized tryptophan (W52, 56, 231, 376, 412, 490,
      522), oxidized methionine (M81, 144, 302, 532, 554, 555), oxidized histidine
      (H214), oxidized proline (P230), oxidized cysteine (C519) and oxidized serine
      (S215). A 20 min irradiation in the presence of methylene blue resulted in 17%
      loss of BChE activity, suggesting that BChE is relatively resistant to methylene
      blue-catalyzed photoinactivation and that therefore this process could be used to
      sterilize BChE preparations.

PMID- 23136925
TI  - Chemically isolating hot spots on concave nanocubes.
AB  - We report a simple and general strategy for selectively exposing and
      functionalizing the sharp corners of concave nanocubes, which are the SERS hot
      spots for such structures. This strategy takes advantage of the unique shape of
      the concave cubes by coating the particles with silica and then etching it away
      to expose only the corner regions, while maintaining the silica coating in the
      concave faces. These corner regions can then be selectively modified for improved
      enhancement and signal response with SERS.

PMID- 23136926
TI  - Relationship between community prevalence of obesity and associated behavioral
      factors and community rates of influenza-related hospitalizations in the United
      States.
AB  - BACKGROUND: Findings from studies examining the association between obesity and
      acute respiratory infection are inconsistent. Few studies have assessed the
      relationship between obesity-related behavioral factors, such as diet and
      exercise, and risk of acute respiratory infection. OBJECTIVE: To determine
      whether community prevalence of obesity, low fruit/vegetable consumption, and
      physical inactivity are associated with influenza-related hospitalization rates.
      METHODS: Using data from 274 US counties, from 2002 to 2008, we regressed county
      influenza-related hospitalization rates on county prevalence of obesity (BMI >=
      30), low fruit/vegetable consumption (<5 servings/day), and physical inactivity
      (<30 minutes/month recreational exercise), while adjusting for community-level
      confounders such as insurance coverage and the number of primary care physicians
      per 100,000 population. RESULTS: A 5% increase in obesity prevalence was
      associated with a 12% increase in influenza-related hospitalization rates
      [adjusted rate ratio (ARR) 1.12, 95% confidence interval (CI) 1.07, 1.17].
      Similarly, a 5% increase in the prevalence of low fruit/vegetable consumption and
      physical inactivity was associated with an increase of 12% (ARR 1.12, 95% CI
      1.08, 1.17) and 11% (ARR 1.11, 95% CI 1.07, 1.16), respectively. When all three
      variables were included in the same model, a 5% increase in prevalence of
      obesity, low fruit/vegetable consumption, and physical inactivity was associated
      with 6%, 8%, and 7% increases in influenza-related hospitalization rates,
      respectively. CONCLUSIONS: Communities with a greater prevalence of obesity were
      more likely to have high influenza-related hospitalization rates. Similarly, less
      physically active populations, with lower fruit/vegetable consumption, tended to
      have higher influenza-related hospitalization rates, even after accounting for
      obesity.

PMID- 23136927
TI  - A multicentre study to determine the value and safety of drug patch tests for the
      three main classes of severe cutaneous adverse drug reactions.
AB  - BACKGROUND: Drug patch tests (PTs) can reproduce delayed hypersensitivity to
      drugs and entail a moderate re-exposure of patients to offending drugs.
      OBJECTIVES: To determine the value of PTs for identifying the responsible drug in
      severe cutaneous adverse drug reactions (SCARs) such as acute generalized
      exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic
      symptoms (DRESS) and Stevens-Johnson syndrome/toxic epidermal necrolysis
      (SJS/TEN). METHODS: In a multicentre study, PTs were conducted on patients
      referred for DRESS, AGEP or SJS/TEN within 1 year of their SCAR. All drugs
      administered in the 2 months prior to and the week following the onset of the
      SCAR were tested. RESULTS: Among the 134 patients included (48 male, 86 female;
      mean age 51.7 years), positive drug PTs were obtained for 24 different drugs.
      These included positive tests for 64% (46/72) of patients with DRESS, 58% (26/45)
      of those with AGEP and 24% (4/17) of those with SJS/TEN, with only one relapse of
      AGEP. The value of PTs depended on the type of drug and the type of SCAR (e.g.
      carbamazepine was positive in 11/13 DRESS cases but none of the five SJS/TEN
      cases). PTs were frequently positive for beta lactams (22 cases), pristinamycin
      (11 cases) and in DRESS with pump proton inhibitors (five cases), but were
      usually negative for allopurinol and salazopyrin. Of 18 patients with DRESS,
      eight had virus reactivation and positive PTs. In DRESS, multiple drug reactivity
      was frequent (18% of cases), with patients remaining sensitized many years later.
      CONCLUSIONS: PTs are useful and safe for identifying agents inducing SCAR.

PMID- 23136928
TI  - Free base and metal complexes of 5,15-diaza-10,20-dimesitylporphyrins: synthesis,
      structures, optical and electrochemical properties, and aromaticities.
AB  - The synthesis, structures, optical and electrochemical properties, and
      aromaticity of a series of 5,15-diaza-10,20-dimesitylporphyrins (M-DAP; M = Pb,
      H(2), Ni, Pd, Pt, Zn; mesityl = 2,4,6-trimethylphenyl) are reported. Treatment of
      mesityl-substituted bis(5,5'-dibromodipyrrin) with sodium azide in the presence
      of lead(II) acetylacetonate afforded Pb-DAP, which was quantitatively converted
      to H(2)-DAP by acidolysis. The free base H(2)-DAP reacted with palladium(II),
      platinum(II), and zinc(II) salts to give Pd-DAP, Pt-DAP, and Zn-DAP,
      respectively. The crystal structures, optical and electrochemical properties, and
      aromaticities of these beta-unsubstituted M-DAPs were comprehensively
      investigated by X-ray crystallography, UV-vis absorption/fluorescence
      spectroscopy, nanosecond flash photolysis, cyclic and differential pulse
      voltammetry, NMR spectroscopy, and density functional theory calculations. The
      obtained data show that  replacement of the 5- and 15-methine carbons with
      nitrogen atoms alters the intrinsic properties of the porphyrin 18pi system as
      follows: (i) the coordination spheres at the N(4) core become contracted while
      keeping high planarity; (ii) the Q bands are red shifted and largely intensified;
      (iii) the electron-accepting ability is enhanced, whereas the electron-donating
      ability is reduced; (iv) the radiative decay rates from the S(1) state are
      enhanced; and (v) the aromaticity of the 18pi circuit is slightly reduced in
      terms of both geometric and magnetic criteria. These optical and electrochemical
      properties of M-DAPs stem from their characteristic frontier orbitals; two HOMOs
      and two LUMOs are nondegenerate as a result of the incorporation of the
      electronegative nitrogen atoms at the two meso positions. In addition, the group
      10 metals incorporated at the core finely tune the fundamental properties of DAP
      pi systems through inductive effects as well as dpi-ppi antibonding orbital
      interactions; the HOMO-LUMO gaps of the group 10 metal complexes increase in the
      order Ni-DAP < Pd-DAP < Pt-DAP.

PMID- 23136929
TI  - The 5x1 DAFNE study protocol: a cluster randomised trial comparing a standard 5
      day DAFNE course delivered over 1 week against DAFNE training delivered over 1
      day a week for 5 consecutive weeks.
AB  - BACKGROUND: Structured education programmes are now established as an essential
      component to assist effective self-management of diabetes. In the case of Type 1
      diabetes, the Dose Adjustment For Normal Eating (DAFNE) programme improves both
      glycaemic control and quality of life. Traditionally delivered over five
      consecutive days, this format has been cited as a barrier to participation by
      some patients, such as those who work full-time. Some centres in the UK have
      organised structured education programmes to be delivered one day a week over
      several consecutive weeks. This type of format may add benefit by allowing more
      time in which to practice skills between sessions, but may suffer as a result of
      weaker peer support being generated compared to that formed over five consecutive
      days. METHODS/DESIGN: We aim to compare DAFNE delivered over five consecutive
      days (1 week course) with DAFNE delivered one day a week over five weeks (5 week
      course) in a randomised controlled trial. A total of 213 patients were randomised
      to attend either a 1 week or a 5 week course delivered in seven participating
      centres. Study outcomes (measured at baseline, 6 and 12 months post-course)
      include HbA1c, weight, self-reported rates of severe hypoglycaemia, psychosocial
      measures of quality of life, and cost-effectiveness. Generalisability was
      optimised by recruiting patients from DAFNE waiting lists at each centre, and by
      mailing eligible patients from hospital clinic lists. The inclusion and exclusion
      criteria were identical to those used to recruit to a standard DAFNE course
      (e.g., HbA1c <12%, with no lower limit). Qualitative interviews were undertaken
      with a sub-sample of n=30 patients and their course educators (n=11) to help
      understand and interpret differences and similarities in outcomes between the 
      two arms, and to identify logistical problems and unanticipated issues arising
      from the adaptation and delivery of  a 5 week course. DISCUSSION: This trial has
      been designed to test the hypothesis that the benefits of delivering a structured
      education programme over 5 weeks are comparable to those observed after a 1 week
      course. The results of the trial and the qualitative sub-study will both inform
      the design and delivery of future DAFNE courses, and the development of
      structured education programmes in other fields of medicine. TRIAL REGISTRATION:
      Clinicaltrials.gov NCT01069393.

PMID- 23136930
TI  - Outcome measures for manual lung hyperinflation: not there yet!

PMID- 23136931
TI  - Decoding of emotional components in complex communicative situations (irony) and
      its relation to empathic abilities in male chronic alcoholics: an issue for
      treatment.
AB  - BACKGROUND: Previous research has shown that deficits in the domain of emotions
      strongly characterize alcoholism. Patients diagnosed with alcoholism show
      impairments in emotional mimic recognition, as well as in the domain of emotional
      prosody. These data suggest that male alcoholics might suffer from a generalized
      emotional impairment associated with dysfunctions in empathy. Taken altogether,
      those deficits might influence alcoholics' relational domain and their
      performance in complex communicative situations such as ironic interactions. The
      present study investigates the ability of chronic male alcoholics to recognize
      the emotional component of ironic contexts and its relation to the comprehension
      of ironic meaning as a function of their empathic abilities. METHODS: Forty-four
      male subjects participated in a story comprehension task. They were asked to read
      stories with either an ironic or a nonironic ending. Participants were asked to
      fill in a questionnaire about communicative intentions and the emotional states
      of the stories' characters. Moreover, the correct comprehension of the ironic
      meaning was assessed through a self-reported questionnaire and related to the
      empathy quotient (EQ) which was measured in a preexperimental phase. RESULTS:
      Alcoholic subjects showed a lower EQ in comparison to healthy subjects and
      recognized significant fewer ironic endings. Social skills results were
      particularly impaired. The correlation between EQ and ironic endings recognition
      was significant. Moreover, alcoholics showed a tendency to attribute positive
      emotions to both ironic and nonironic contexts, showing an opposite pattern in
      comparison with control subjects who tended to associate negative emotions to
      ironic contexts. CONCLUSIONS: The present study indicates that emotional
      recognition deficits that have been previously observed in chronic alcoholics
      extend to complex interactive contexts. This deficit is associated with a more
      general impairment of empathy, especially in its social skill component. Clinical
      implications of the present results are discussed.

PMID- 23136932
TI  - Impact of renal function and demographic/anthropomorphic variables on peak
      thyrotropin after recombinant human thyrotropin stimulation: a stepwise forward
      multiple-regression analysis.
AB  - BACKGROUND: When applying the recommended standard doses of recombinant human
      thyrotropin (rhTSH) in the diagnostic/therapeutic management of patients with
      differentiated thyroid cancer (DTC), the resulting peak TSH levels vary
      extensively. Previous studies applying multivariate statistics identified patient
      inherent variables influencing the rhTSH/peak TSH relation. However, those
      results were inconclusive and partly conflicting. Notably, no independent role of
      renal function was substantiated, despite the fact that the kidneys are known to
      play a prominent role in TSH clearance from blood. Therefore, the study's aim was
      to investigate the impact of renal function on the peak TSH concentration after
      the standard administration of rhTSH used in the management of thyroid cancer.
      The second objective was to calculate a ranking regarding the effect sizes of the
      selected variables on the peak TSH. METHODS: There were 286 patients with DTC
      included in the study. Univariate and multivariate analyses were performed,
      testing the correlation of serum creatinine and glomerular filtration rate (GFR)
      as surrogate parameters of renal function, age, sex, weight, height, and body
      surface area (BSA) with the peak TSH level. In six additional patients, the
      subsequent TSH pharmacokinetics after the TSH peak were measured and
      qualitatively compared. RESULTS: By univariate analyses, TSH correlated
      negatively with BSA, GFR, weight, and height, and positively with age, female
      sex, and serum creatinine (p<0.001). On the multivariate analysis, the stepwise
      forward multiple linear regression revealed BSA and renal function as the two
      most influential independent variables, followed by age, sex, and height. The
      pharmacokinetic datasets indicated that these identified parameters also
      influence the TSH decline over time. CONCLUSION: Identifying those patients with
      a favorable combination of parameters predicting a high-peak TSH is the first
      step toward an individualization of rhTSH dosing. Additionally, the subsequent
      TSH decrease over time needs to be taken into account. A complete understanding
      of the interrelation of the identified key parameters and both the TSH peak and
      subsequent TSH pharmacokinetics might allow for a more personalized rhTSH dosage
      strategy to achieve sufficient TSH levels instead of the fixed dosing procedure
      used at present.

PMID- 23136933
TI  - Design of a single-tube, endpoint, linear-after-the-exponential-PCR assay for 17
      pathogens associated with sepsis.
AB  - AIMS: The goal of this study was to construct a single-tube multiplex molecular
      diagnostic assay using linear-after-the-exponential (LATE)-PCR for the detection
      of 17 microbial pathogens commonly associated with septicaemia. METHODS AND
      RESULTS: The assay described here detects 17 pathogens associated with sepsis via
      amplification and analysis of gene-specific sequences. The pathogens and their
      targeted genes were: Klebsiella spp. (phoE); Acinetobacter baumannii (gyrB);
      Staphylococcus aureus (spa); Enterobacter spp. (thdF); Pseudomonas aeruginosa
      (toxA); coagulase-negative staphylococci (tuf), Enterococcus spp. (tuf); Candida
      spp. (P450). A sequence from an unidentified gene in Lactococcus lactis, served
      as a positive control for assay function. LATE-PCR was used to generate single
      stranded amplicons that were analysed at endpoint over a wide range of
      temperatures in four fluorescent colours. Each target was detected by its pattern
      of hybridization to a sequence-specific low-temperature fluorescent probe derived
      from molecular beacons. CONCLUSIONS: All 17 microbial targets were detected in
      samples containing low numbers of pathogen genomes in the presence of high levels
      of human genomic DNA. SIGNIFICANCE AND IMPACT OF THE STUDY: This assay used new
      technology to achieve an advance in the field of molecular diagnostics: a single
      tube assay for detection of pathogens commonly responsible for septicaemia.

PMID- 23136934
TI  - Heterotrimeric guanosine triphosphate-binding protein-coupled modulatory actions
      of motilin on K+ channels and postsynaptic gamma-aminobutyric acid receptors in
      mouse medial vestibular nuclear neurons.
AB  - Some central nervous system neurons express receptors of gastrointestinal
      hormones, but their pharmacological actions are not well known. Previous
      anatomical and unit recording studies suggest that a group of cerebellar Purkinje
      cells express motilin receptors, and motilin depresses the spike discharges of
      vestibular nuclear neurons that receive direct cerebellar inhibition in rats or
      rabbits. Here, by the slice-patch recording method, we examined the
      pharmacological actions of motilin on the mouse medial vestibular nuclear neurons
      (MVNs), which play an important role in the control of ocular reflexes. A small
      number of MVNs, as well as cerebellar floccular Purkinje cells, were labeled with
      an anti-motilin receptor antibody. Bath application of motilin (0.1 MUm)
      decreased the discharge frequency of spontaneous action potentials in a group of
      MVNs in a dose-dependent manner (K(d) , 0.03 MUm). The motilin action on
      spontaneous action potentials was blocked by apamin (100 nm), a blocker of small
      conductance Ca(2+) -activated K(+) channels. Furthermore, motilin enhanced the
      amplitudes of inhibitory postsynaptic currents (IPSCs) and miniature IPSCs, but
      did not affect the frequencies of miniature IPSCs. Intracellular application of
      pertussis toxin (PTx) (0.5 MUg/MUL) or guanosine triphosphate-gamma-S (1 mm)
      depressed the motilin actions on both action potentials and IPSCs. Only 30% of
      MVNs examined on slices obtained from wild-type mice, but none of the GABAergic
      MVNs that were studied on slices obtained from vesicular gamma-aminobutyric acid
      transporter-Venus transgenic mice, showed such a motilin response on action
      potentials and IPSCs. These findings suggest that motilin could modulate small
      conductance Ca(2+) -activated K(+) channels and postsynaptic gamma-aminobutyric
      acid receptors through heterotrimeric guanosine triphosphate-binding protein
      coupled receptor in a group of glutamatergic MVNs.

PMID- 23136935
TI  - Changes over time in craniocerebral morphology and syringomyelia in cavalier King
      Charles spaniels with Chiari-like malformation.
AB  - BACKGROUND: Chiari-like malformation (CM) and syringomyelia is a neurological
      disease complex with high prevalence in cavalier King Charles spaniels (CKCS).
      The natural progression of this disease with time has not been described. The
      objectives of this study were to i) determine if syringomyelia progresses with
      time ii) determine if features of craniocrebral morphology previously associated
      with CM are progressive (including caudal cranial fossa volume, caudal cranial
      fossa parenchymal volume, ventricular dimensions, height of the foramen magnum
      and degree of cerebellar herniation). A retrospective morphometric analysis was
      undertaken in 12 CKCS with CM for which repeat magnetic resonance images were
      available without surgical intervention. RESULTS: The maximal syrinx width,
      height of the foramen magnum, length of cerebellar herniation and caudal cranial
      fossa volume increased over time. Ventricular and caudal fossa parenchymal
      volumes were not significantly different between scans. CONCLUSIONS: The results
      of this study suggest that syringomyelia progresses with time. Increased caudal
      cranial fossa volume may be associated with active resorption of the
      supraoccipital bone, which has previously been found in histology specimens from
      adult CKCS. We hypothesise that active resorption of the supraoccipital bone
      occurs due to pressure from the cerebellum. These findings have important
      implications for our understanding of the pathogenesis and variable natural
      clinical progression of CM and syringomyelia in CKCS.

PMID- 23136936
TI  - A prospective study to examine the epidemiology of methicillin-resistant
      Staphylococcus aureus and Clostridium difficile contamination in the general
      environment of three community hospitals in southern Ontario, Canada.
AB  - BACKGROUND: The hospital environment has been suggested as playing an important
      role in the transmission of hospital-associated (HA) pathogens. However, studies
      investigating the contamination of the hospital environment with methicillin
      resistant Staphylococcus aureus (MRSA) or Clostridium difficile have generally
      focused on point prevalence studies of only a single pathogen. Research
      evaluating the roles of these two pathogens, concurrently, in the general
      hospital environment has not been conducted. The objectives of this study were to
      determine the prevalence and identify risk factors associated with MRSA and C.
      difficile contamination in the general environment of three community hospitals,
      prospectively. METHODS: Sampling of environmental surfaces distributed over the
      medicine and surgical wards at each hospital was conducted once a week for four
      consecutive weeks. Sterile electrostatic cloths were used for environmental
      sampling and information regarding the surface sampled was recorded. For MRSA,
      air sampling was also conducted. Enrichment culture was performed and spa typing
      was performed for all MRSA isolates. For C. difficile, isolates were
      characterized by ribotyping and investigated for the presence of toxin genes by
      PCR. Using logistic regression, the following risk factors were examined for MRSA
      or C. difficile contamination: type of surface sampled, surface material, surface
      location, and the presence/absence of the other HA pathogen under investigation.
      RESULTS: Overall, 11.8% (n=612) and 2.4% (n=552) of surfaces were positive for
      MRSA and C. difficile, respectively. Based on molecular typing, five different
      MRSA strains and eight different C. difficile ribotypes, including ribotypes 027
      (15.4%) and 078 (7.7%), were identified in the hospital environment. Results from
      the logistic regression model indicate that compared to computer keyboards, the
      following surfaces had increased odds of being contaminated with MRSA: chair
      backs, hand rails, isolation carts, and sofas. CONCLUSIONS: MRSA and C. difficile
      were identified from a variety of surfaces in the general hospital
      environment.Several surfaces had an increased risk of being contaminated with
      MRSA but further studies regarding contact rates, type of surface material, and
      the populations using these surfaces are warranted.

PMID- 23136937
TI  - Temperature and force dependence of nanoscale electron transport via the Cu
      protein azurin.
AB  - Solid-state electron transport (ETp) via a monolayer of immobilized azurin (Az)
      was examined by conducting probe atomic force microscopy (CP-AFM), as a function
      of both temperature (248-373K) and applied tip force (6-15 nN). At low forces,
      ETp via holo-Az (with Cu(2+)) is temperature-independent, but thermally activated
      via the Cu-depleted form of Az, apo-Az. While this observation agrees with those
      of macroscopic-scale measurements, we find that for holo-Az the mechanism of ETp
      at high temperatures changes upon an increase in the force applied by the tip to
      the proteins; namely, above 310 K and forces >6 nN ETp becomes thermally
      activated. This is in contrast to apo-Az, where increasing applied force causes
      only small monotonic increases in currents due to decreased electrode separation.
      The distinct ETp temperature dependence of holo- and apo-Az is assigned to a
      difference in structural response to pressure between the two protein forms. An
      important implication of these CP-AFM results (of measurements over a significant
      temperature range) is that for reliable ETp measurements on flexible
      macromolecules, such as proteins, the pressure applied during the measurements
      should be controlled or at least monitored.

PMID- 23136938
TI  - Association between genetic polymorphisms of NOD 1 and Helicobacter pylori
      induced gastric mucosal inflammation in healthy Korean population.
AB  - BACKGROUND: Gastric cancer is supposed to be a result of inflammation induced by
      Helicobacter pylori (H. pylori) infection. Nucleotide-binding oligomerization
      domain 1 (NOD 1) is required for the innate immune response to H. pylori. We aim
      to investigate whether single nucleotide polymorphism (SNP) in NOD 1 gene is
      associated with H. pylori-induced gastric mucosal inflammation in a healthy
      Korean population. METHODS: The study was conducted on 412 adults who visited two
      different healthcare centers for health examinations. The G796A (E266K) NOD 1 SNP
      was detected by using polymerase chain reaction/restriction fragment length
      polymorphism. A gastritis score was calculated by the summed values of the grade
      and the activity of gastritis scored according to the updated Sydney system. The
      expression of IL-8 and COX-2 mRNA was assessed by quantitative reverse
      transcription polymerase chain reaction. In the group with H. pylori infection,
      the complete screening of the genes comprising the cag PAI was performed.
      RESULTS: The genotype frequencies were 26.7% (AA type), 58.3% (GA), and 15.0%
      (GG). In H. pylori-positive patients, gastritis score of the AA genotype was
      significantly higher than those of the others (p = .04). Also, the IL-8 and COX-2
      mRNA levels increased in the AA genotype. In the group with H. pylori infection,
      31.9% were found to carry the complete cag PAI. When the subjects were infected
      with intact cag PAI, the IL-8 and COX-2 mRNA levels were significantly high in AA
      genotype. CONCLUSION: G796A (E266K) NOD 1 polymorphism is closely correlated with
      H. pylori-associated gastric mucosal inflammation in the Korean population.

PMID- 23136940
TI  - N-silyloxaziridines: synthesis and use for electrophilic amination.
AB  - N-Silyloxaziridines were synthesized for the first time. Their tert
      butyldiphenylsilyl (TBDPS) derivatives were stable reagents that were prepared on
      a multigram scale in three steps and in 44% overall yield from the corresponding
      benzylamines. They were mild electrophilic aminating reagents that reacted at
      room temperature with diversely substituted primary and secondary amines to
      produce N-monoalkyl or N,N-dialkyl benzaldehyde hydrazones in 44-87% yield.

PMID- 23136939
TI  - Maternal occupational exposure to polycyclic aromatic hydrocarbons and risk of
      oral cleft-affected pregnancies.
AB  - OBJECTIVE: To evaluate whether there is an association between maternal
      occupational exposure to polycyclic aromatic hydrocarbons and oral clefts in
      offspring. This is the first human study of polycyclic aromatic hydrocarbons and
      clefts of which the authors are aware. DESIGN: Case-control study. SETTING,
      PARTICIPANTS: Data for 1997 to 2002 from the National Birth Defects Prevention
      Study, a large population-based case-control study in the United States, were
      analyzed. Maternal telephone interviews yielded information on jobs held in the
      month before through 3 months after conception. Two industrial hygienists
      independently assessed occupational exposure to polycyclic aromatic hydrocarbons;
      all jobs rated as exposed or with rating difficulty were reviewed with a third
      industrial hygienist to reach consensus on all exposure parameters. Logistic
      regression estimated crude and adjusted odds ratios with 95% confidence intervals
      for cleft lip with or without cleft palate and cleft palate alone. RESULTS: There
      were 2989 controls (3.5% exposed), 805 cases of cleft lip with or without cleft
      palate (5.8% exposed), and 439 cases of cleft palate alone (4.6% exposed). The
      odds of maternal occupational exposure to polycyclic aromatic hydrocarbons (any
      versus none) during pregnancy was increased for cleft lip with or without cleft
      palate cases as compared with controls (odds ratio, 1.69; 95% confidence
      interval, 1.18 to 2.40); the odds ratio was 1.47 (95% confidence interval 1.02 to
      2.12) when adjusted for maternal education. There was a statistically significant
      adjusted exposure-response relationship for cleft lip with or without cleft
      palate (Ptrend = .02). Odd ratios for cleft palate alone were not statistically
      significant. CONCLUSIONS: Maternal occupational exposure to polycyclic aromatic
      hydrocarbons was associated with increased risk of cleft lip with or without
      cleft palate in offspring.

PMID- 23136941
TI  - Nematotoxic phenolic compounds from Melia azedarach against Meloidogyne
      incognita.
AB  - In the present study, evaluated was the paralysis activity of whole Italian and
      Algerian Melia azedarach, commonly known as chinaberry, fruits and parts (seeds,
      wood, and kernels) against Meloidogyne incognita second stage juveniles (J(2)).
      The paralysis activity was evaluated in vitro after 1 h and 1 day immersion
      periods of nematodes in test solutions. Phenolic constituent components of the
      extracts were identified and quantified by high-performance liquid chromatography
      mass spectrometry, while confirmation was performed by high-performance liquid
      chromatography-diode array. The water extract of the Italian M. azedarach fruit
      pulp (IPWE) showed significant nematicidal activity (EC(50/48h) = 955 MUg/mL) and
      among its active ingredient components were p-coumaric acid and p-hydroxybenzoic
      acid (EC(50/48h) = 840 and 871 MUg/mL, respectively). This is the first report of
      the nematicidal activity of M. azedarach pulp water extract and phenolic acids
      against the root knot nematode M. incognita.

PMID- 23136942
TI  - Uric acid modulates vascular endothelial function through the down regulation of
      nitric oxide production.
AB  - Endothelial dysfunction characterized by decreased nitric oxide (NO)
      bioavailability is the first stage of coronary artery disease. It is known that
      one of the factors associated with an increased risk of coronary artery disease
      is a high plasma level of uric acid. However, causative associations between
      hyperuricaemia and cardiovascular risk have not been definitely proved. In this
      work, we tested the effect of uric acid on endothelial NO bioavailability.
      Electrochemical measurement of NO production in acetylcholine-stimulated human
      umbilical endothelial cells (HUVECs) revealed that uric acid markedly decreases
      NO release. This finding was confirmed by organ bath experiments on mouse aortic
      segments. Uric acid dose-dependently reduced endothelium-dependent
      vasorelaxation. To reveal the mechanism of decreasing NO bioavailability we
      tested the effect of uric acid on reactive oxygen species production by HUVECs,
      on arginase activity, and on acetylcholine-induced endothelial NO synthase
      phosphorylation. It was found that uric acid increases arginase activity and
      reduces endothelial NO synthase phosphorylation. Interestingly, uric acid
      significantly increased intracellular superoxide formation. In conclusion, uric
      acid decreases NO bioavailability by means of multiple mechanisms. This finding
      supports the idea of a causal association between hyperuricaemia and
      cardiovascular risk.

PMID- 23136943
TI  - Changes of the phenol-degrading bacterial community during the decomposition of
      submersed Platanus acerifolia leaves.
AB  - Microorganisms are responsible for the decomposition of plant litter due to their
      enhanced enzyme capabilities. Among extracellular enzymes, those involved in
      lignin decomposition are especially relevant in leaf degradation. However, the
      knowledge of the bacterial contribution to the decomposition of phenol-derived
      compounds in submerged leaf litter is limited. We have used the large unit of the
      multicomponent bacterial phenol hydroxylase (LmpH) as a genetic proxy to describe
      changes in the phenol-degrading bacterial community during the decomposition of
      Platanus acerifolia leaves in a forested stream. Significant differences were
      found in the phenol-degrading community when three decomposition stages, initial
      (day 7), midterm (day 58), and late (day 112), were compared. Estimated Shannon's
      diversity values decreased significantly from 1.93 (initial) to 0.98 (late).
      According to the deduced amino acid sequences and the corresponding theoretical
      kinetic parameters of phenol hydroxylases, the initial community showed a low
      degree of specialization, presumably resulting from random colonization of
      leaves. At the late decomposition stage, the bacterial community became more
      specialized, and LmpH genes similar to high-affinity phenol hydroxylases of
      Comamonas sp. and Burkholderia cepacia increased. The observed changes in the
      bacterial community suggested an active role of bacteria during litter
      decomposition in aquatic environments.

PMID- 23136944
TI  - Cubic box versus spheroidal capsule built from defect and intact pentagonal
      units.
AB  - The high-nuclearity polyoxothiomolybdate
      [H(8)Mo(84)S(48)O(188)(H(2)O)(12)(CH(3)COO)(24)](32-) has been prepared and
      characterized by single-crystal X-ray crystallography and (1)H NMR, IR, Raman,
      and UV-vis spectroscopy. The solid-state structure reveals an unprecedented and
      intriguing arrangement consisting of a nanoscaled anionic cube. The surprisingly
      open structure of this {Mo(84)}-type cubic box features a large inner void that
      is accessible via its six open square faces with diameters of ca. 9 A.
      Importantly, this molecular system appears to be highly functionalizable because
      of the presence of 24 exposed exchangeable acetate ligands.

PMID- 23136945
TI  - The dose-response relationship for dicentric chromosomes and gamma-H2AX foci in
      human peripheral blood lymphocytes: influence of temperature during exposure and
      intra- and inter-individual variability of donors.
AB  - PURPOSE: Hypothermia during in vitro irradiation of human peripheral blood
      lymphocytes (PBL) affects the level of chromosome aberrations. The molecular
      mechanisms of this phenomenon are not fully understood. The aim of our study was
      to examine the effect of hypothermia on the dose-response relationship for
      dicentric chromosomes and the level of gamma-H2AX (phosphorylated histone H2AX)
      foci. In addition, the inter- and intra-individual variability was assessed in
      relation to temperature. MATERIALS AND METHODS: PBL were kept at 0.8, 20 and 37
      degrees C and then exposed to gamma-rays (from 0-3 Gy). Dicentric chromosomes
      were scored in first post-treatment mitoses. gamma-H2AX foci were scored 15, 30,
      60, 120 min and 24 h post irradiation. RESULTS: Our results revealed that the
      frequency of dicentric chromosomes in cells exposed at 37 degrees C to gamma-rays
      was higher than after exposure at 0.8 and 20 degrees C. No effect of temperature
      was observed on the number of gamma-H2AX foci as well as on the intra- and inter
      individual variations of the dicentric yield and the number of gamma-H2AX foci.
      CONCLUSIONS: Temperature at exposure to ionizing radiation has a pronounced
      effect on the level of cytogenetic damage but not gamma-H2AX foci.

PMID- 23136946
TI  - Influence of dyslipidemia and diabetes mellitus on chronic periodontal disease.
AB  - BACKGROUND: Periodontal disease is closely related to certain systemic
      conditions, such as type 2 diabetes mellitus (DM2), and, as recently described,
      dyslipidemia, a condition with alterations in blood lipids levels. However, more
      than acting as disease modifiers, these conditions commonly occur as
      comorbidities, possibly synergically affecting periodontal tissues. The aim of
      the current study is to identify whether DM2 and dyslipidemia are related to the
      occurrence and severity of chronic periodontitis. METHODS: A total of 254
      individuals participated: 56 were patients with DM2, 67 had dyslipidemia, 74 had
      DM2 and dyslipidemia, and 57 were systemically healthy individuals. The clinical
      examination included a full-mouth evaluation of periodontal probing depth, plaque
      score, bleeding on probing, and clinical attachment level (CAL). Blood samples
      were taken to assess fasting plasma glucose, low-density lipoprotein, high
      density lipoprotein, and triglyceride levels. These parameters, as well as other
      medical conditions (i.e., smoking habits and body mass index), were considered in
      multiple regression analyses for data analyses (alpha = 5%). RESULTS:
      Dyslipidemia was not related to periodontal disease (P >0.05). At the same time,
      DM2, age, and smoking showed a statistical and positive association, an increase
      in percentage of sites with CAL >=3 and >=5 mm. Regarding the percentage of sites
      presenting severe destruction (CAL >=7 mm), only DM2 remained a significant risk
      factor (P <0.05). CONCLUSIONS: It could be concluded that dyslipidemia did not
      influence periodontal conditions in participants with normal health or those with
      DM2. However, age, smoking habits, and especially DM2 were significantly
      associated with loss of CAL.

PMID- 23136947
TI  - MyD88 or TRAM knockdown regulates interleukin (IL)-6, IL-8, and CXCL12 mRNA
      expression in human gingival and periodontal ligament fibroblasts.
AB  - BACKGROUND: In a previous report, it was shown that Toll-like receptor (TLR) 2
      knockdown modulates interleukin (IL)-6 and IL-8 but not the chemokine CXCL12, an
      important mediator with inflammatory and proangiogenic effects, in human gingival
      fibroblasts (HGF) and human periodontal ligament fibroblasts (HPDLF). This study
      investigates whether knocking down two important TLR adaptor molecules, such as
      myeloid differentiation protein 88 (MyD88) and TRIF-related adaptor molecule
      (TRAM), could affect mRNA expression of IL-6, IL-8, and CXCL12 in HGF and HPDLF.
      METHODS: After small interfering (si) RNA-mediated silencing of MyD88 or TRAM,
      HGF and HPDLF were stimulated with Porphyromonas gingivalis (Pg)
      lipopolysaccharide (LPS) or two synthetic ligands of TLR2 (Pam2CSK4 and Pam3CSK4)
      for 6 hours. IL-6, IL-8, and CXCL12 mRNAs were evaluated by quantitative
      polymerase chain reaction. RESULTS: Knockdown of MyD88 or TRAM partially impaired
      the IL-8 mRNA upregulation in both fibroblast subpopulations. Similarly, IL-6
      upregulation was partially prevented by siMyD88 or siTRAM in HGF stimulated with
      Pg LPS, as well as in both fibroblast subtypes challenged with Pam2CSK4.
      Conversely, constitutive CXCL12 mRNA levels were upregulated by MyD88 or TRAM
      knockdown in non-stimulated cells. CONCLUSIONS: These results suggest that TLR
      adaptor molecules knockdown, such as MyD88 or TRAM, can decrease IL-6 and IL-8
      mRNA and increase CXCL12 mRNA expression in HGF and HPDLF. This can be an
      important step for better understanding the mechanisms that control the
      inflammatory cytokine and chemokine expression, which in turn contributes to
      periodontal pathogenesis.

PMID- 23136948
TI  - Periodontal and general health in long-term periodontal maintenance patients
      treated in a Norwegian private practice: a descriptive report from a compliant
      and partially compliant survivor population.
AB  - BACKGROUND: There is weak evidence to support the benefit of periodontal
      maintenance therapy in preventing tooth loss. In addition, the effects of long
      term periodontal treatment on general health are unclear. METHODS: Patients who
      were compliant and partially compliant (15 to 25 years' follow-up) in private
      practice were observed for oral and systemic health changes. RESULTS: A total of
      219 patients who were compliant (91 males and 128 females) were observed for 19.1
      (range 15 to 25; SD +/- 2.8) years. Age at reassessment was 64.6 (range: 39 to
      84; SD +/- 9.0) years. A total of 145 patients were stable (0 to 3 teeth lost),
      54 were downhill (4 to 6 teeth lost), and 21 patients extreme downhill (>6 teeth
      lost); 16 patients developed hypertension, 13 developed type 2 diabetes, and 15
      suffered myocardial infarcts (MIs). A minority developed other systemic diseases.
      Risk factors for MI included overweight (odds ratio [OR]: 9.04; 95% confidence
      interval [CI]: 2.9 to 27.8; P = 0.000), family history with cardiovascular
      disease (OR: 3.10; 95% CI: 1.07 to 8.94; P = 0.029), type 1 diabetes at baseline
      (P = 0.02), and developing type 2 diabetes (OR: 7.9; 95% CI: 2.09 to 29.65; P =
      0.000). A total of 25 patients who were partially compliant (17 males and eight
      females) were observed for 19 years. This group had a higher proportion of
      downhill and extreme downhill cases and MI. CONCLUSIONS: Patients who left the
      maintenance program in a periodontal specialist practice in Norway had a higher
      rate of tooth loss than patients who were compliant. Patients who were compliant
      with maintenance in a specialist practice in Norway have a similar risk of
      developing type 2 diabetes as the general population. A rate of 0.0037 MIs per
      patient per year was recorded for this group. Due to the lack of external data,
      it is difficult to assess how this compares with patients who have periodontal
      disease and are untreated.

PMID- 23136950
TI  - Measuring the ability to perceive the emotional connotations of written language.
AB  - Emotionally laden writing is essential to our personal and professional lives.
      The purpose of this article was to design and evaluate a new test of the ability
      to decode the emotional connotations of written material. A series of 3 studies
      (totaling 457 participants) were used to demonstrate that the Metaphors Test
      measures a single construct, has strong internal consistency, has strong
      convergent validity with tests related to emotional and social intelligence, and
      has strong discriminant validity with vocabulary and personality. Confirmatory
      factor analyses demonstrated that the Metaphors Test is more closely associated
      with emotion perception than emotional understanding. Unlike most other tests
      that tap this skill, the stimuli for the Metaphors Test do not include any
      explicit emotion words; it is therefore a unique and valuable measure of emotion
      perception.

PMID- 23136949
TI  - MicroRNAs as biomarkers in solid organ transplantation.
AB  - Important progress has been made in improving short-term outcomes in solid organ
      transplantation. However, long-term outcomes have not improved during the last
      decades. There is a critical need for biomarkers of donor quality, early
      diagnosis of graft injury and treatment response. MicroRNAs (miRNAs) are a class
      of small single-stranded noncoding RNAs that function through translational
      repression of specific target mRNAs. MiRNA expression has been associated with
      different diseases and physiological conditions. Moreover, miRNAs have been
      detected in different biological fluids and these circulating miRNAs can
      distinguish diseased individuals from healthy controls. The noninvasive nature of
      circulating miRNA detection, their disease specificity and the availability of
      accurate techniques for detecting and monitoring these molecules has encouraged a
      pursuit of miRNA biomarker research and the evaluation of specific applications
      in the transplant field. miRNA expression might develop as excellent biomarkers
      of allograft injury and function. In this minireview, we summarize the main
      accomplishments of recently published reports focused on the identification of
      miRNAs as biomarkers in organ quality, ischemia-reperfusion injury, acute
      rejection, tolerance and chronic allograft dysfunction emphasizing their
      mechanistic and clinical potential applications and describing their
      methodological limitations.

PMID- 23136951
TI  - The performance of transient elastography compared to clinical acumen and routine
      tests - what is the incremental diagnostic value?
AB  - BACKGROUND/AIMS: There is substantial evidence suggesting transient elastography
      (TE) is a useful tool in assessing liver fibrosis. We aimed to determine whether
      TE has incremental diagnostic value over clinical acumen and routinely available
      tests. METHODS: We performed a retrospective study of 130 patients to assess the
      ability of hepatologists to predict severity of fibrosis using clinical acumen;
      clinical acumen with routine tests; and elastography in patients with chronic
      liver disease. The incremental diagnostic benefit was assessed using the area
      under the ROC curve (AUC) and the Net Reclassification Index (NRI). RESULTS:
      Using universally available tests, including clinical acumen, the AUCs for
      detection of cirrhosis ranged from 0.70 to 0.80 for the four hepatologists.
      Elastography led to statistically non-significant improvements in AUC statistics
      (range 0.83-0.89; P > 0.01). The detection of significant fibrosis using clinical
      acumen and routine tests was less accurate, with AUCs of 0.52-0.59. Elastography
      had incremental diagnostic value (AUC performance range 0.76-0.82; P < 0.01). The
      NRI indicated that 39-58% were correctly reclassified using elastography,
      especially with respect to sensitivity. CONCLUSIONS: Our study suggests that the
      diagnostic value of clinical acumen and routine tests is acceptable for detection
      of cirrhosis, but not significant fibrosis. Elastography detects significant
      fibrosis or cirrhosis with acceptable accuracy and offered incremental diagnostic
      value in detecting significant fibrosis, but not cirrhosis. These findings have
      implications for determining the diagnostic value of tests over and above routine
      clinical assessment, which will aid incorporation of novel tests into clinical
      algorithms.

PMID- 23136952
TI  - Photoexcited singlet and triplet states of a UV absorber ethylhexyl
      methoxycrylene.
AB  - The excited states of UV absorber, ethylhexyl methoxycrylene (EHMCR) have been
      studied through measurements of UV absorption, fluorescence, phosphorescence and
      electron paramagnetic resonance (EPR) spectra in ethanol. The energy levels of
      the lowest excited singlet (S1) and triplet (T1) states of EHMCR were determined.
      The energy levels of the S1 and T1 states of EHMCR are much lower than those of
      photolabile 4-tert-butyl-4'-methoxydibenzoylmethane. The energy levels of the S1
      and T1 states of EHMCR are lower than those of octyl methoxycinnamate. The weak
      phosphorescence and EPR B(min) signals were observed and the lifetime was
      estimated to be 93 ms. These facts suggest that the significant proportion of the
      S1 molecules undergoes intersystem crossing to the T1 state, and the deactivation
      process from the T1 state is predominantly radiationless. The photostability of
      EHMCR arises from the (3)pipi* character in the T1 state. The zero-field
      splitting (ZFS) parameter in the T1 state is D** = 0.113 cm(-1).

PMID- 23136953
TI  - Regulation of the collisional self-quenching of fluorescence in clay/porphyrin
      complex by strong host-guest interaction.
AB  - This paper proposes a novel methodology to improve noncollisional photochemical
      reactions such as Forster resonance energy transfer on solid surfaces. Since an
      excited guest molecule densely adsorbed on the solid surfaces is quenched by an
      unfavorable interaction between guests in general, the photochemical reactions
      such as electron and energy transfers tend to be inefficient compared to those in
      homogeneous systems. In this work, the mechanism of unfavorable quenching process
      of dyes on the clay surface as a typical solid surface for the photochemical
      energy transfer was systematically investigated by using a series of porphyrin
      derivatives. As a result, it was found that the quenching rate constants of
      excited guest dye determined by the time-resolved fluorescence measurements
      correlated well with the strengths of coulombic interaction between host and
      guest. The strong coulombic interaction should suppress the mobility and
      collision frequency of guests on the clay surface; thus, the collision of guest
      molecules was revealed as the origin of unfavorable quenching for photochemical
      reactions on the clay surface. According to this principle, we will be able to
      construct efficient photochemical reaction systems without any quenching process,
      such as efficient energy transfers toward an artificial light-harvesting system.
      In fact, we have already realized almost 100% energy transfer by the suppression
      of quenching process on the clay surface (e.g., J. Am. Chem. Soc.2011, 133, 14280
      14286).

PMID- 23136955
TI  - Exploring the conformational dynamics of the bovine ADP/ATP carrier in
      mitochondria.
AB  - The mitochondrial ADP/ATP carrier catalyzes the transport of ADP and ATP across
      the mitochondrial inner membrane by switching between two different
      conformations. They can be blocked by two inhibitors: carboxyatractyloside (CATR)
      and bongkrekic acid (BA). Our understanding of the ADP/ATP transport process is
      largely based on analysis of structural differences between the individual
      inhibited states. The X-ray crystallographic three-dimensional structure of
      bovine ADP/ATP carrier isoform 1 (bAnc1p) complexed with CATR was determined, but
      the structure of the BA-carrier complex remains unknown. We recently investigated
      the conformational dynamics of bAnc1p in detergent solution using
      hydrogen/deuterium exchange and mass spectrometry (HDX-MS). This study shed light
      on some features of ADP/ATP translocation, but the mechanism itself and the
      organization of bAnc1p in the membrane required further investigation. This paper
      describes the first study of bAnc1p in the mitochondria on the whole-protein
      scale using HDX-MS. Membrane-embedded bAnc1p was deuterated and purified under
      HDX-MS-compatible conditions. Our results for the carrier in the mitochondrial
      inner membrane differed from those published for the carrier in a detergent
      solution. These differences were mainly in the upper half of the cavity that
      globally showed a limited H/D exchange whatever the complex analyzed and at the
      level of the matrix loops that were less accessible to the solvent in the BA
      carrier complex than in the CATR-carrier complex. They are discussed with respect
      to published data for bAnc1p and have provided new insights into the conformation
      of the matrix loops of the bovine carrier in complex with BA in mitochondria.

PMID- 23136954
TI  - Amaryllidaceae alkaloids inhibit nuclear-to-cytoplasmic export of
      ribonucleoprotein (RNP) complex of highly pathogenic avian influenza virus H5N1.
AB  - BACKGROUND: Few drugs are currently licensed to treat influenza A infection, and
      new therapies are needed, especially for highly pathogenic strains. Traditional
      medicinal plants, such as Lycoris radiata, are a potential source of new
      antiviral agents. OBJECTIVE: To test 15 Amaryllidaceae alkaloids isolated from
      the bulbs of L. radiata in vitro for antiviral activities against influenza virus
      type A, A/Chicken/GuangDong/178/2004 (H5N1, 178). METHODS: Antiviral activities
      of the compounds were tested in time-of-addition assays, hemagglutination
      inhibition (HI) assays, neuraminidase (NA) activity assays, and viral entry
      inhibition assays using H5N1-HIV pseudoviruses. Effects of the compounds on
      localization and activity of the viral ribonucleoprotein (RNP) were determined by
      immunofluorescence and an RNP minigenome assay, respectively. RESULTS: Among the
      alkaloids, lycorine (AA1), hippeastrine (AA2), hemanthamine (AA3) and 11-hydroxy
      vittatine (AA4) exhibited antiviral activities, with EC90 values of 0.52, 82.07,
      4.15, and 13.45 MUm, respectively. These compounds did not affect the function of
      the outer membrane proteins or the viral entry process and viral RNP activity. As
      AA1 and AA3 exhibited stronger antiviral activities, they were further analyzed.
      Intracellular nucleoprotein (NP) localization showed that AA1 and AA3 inhibited
      the RNP complex in the nucleus at an early stage of a single-round and multi
      round of replication. CONCLUSION: Four Amaryllidaceae alkaloids were first
      determined that could exert anti-influenza activities after virus entry into
      cells. Furthermore, AA1 and AA3 could inhibit nuclear-to-cytoplasmic export of
      the RNP complex of virus replication. Thus, these compounds may be developed
      further as anti-influenza drug candidates.

PMID- 23136956
TI  - The role of glutathione S-transferase and claudin-1 gene polymorphisms in contact
      sensitization: a cross-sectional study.
AB  - BACKGROUND: Contact sensitization is frequent in the general population and
      arises from excessive or repeated skin exposure to chemicals and metals. However,
      little is known about its genetic susceptibility. OBJECTIVES: To determine the
      role of polymorphisms of glutathione S-transferase (GST) genes and the claudin-1
      gene (CLDN1) on the risk of contact sensitization, taking common filaggrin gene
      (FLG) mutations into account. METHODS: In total, 3471 adult Danes from the
      general population were standard patch tested and filled out a questionnaire on
      their general health. They were genotyped for the following polymorphisms: GSTM1
      and GSTT1 deletion, GSTP1 single nucleotide polymorphism (SNP) rs1695, four CLDN1
      SNPs (rs893051, rs9290927, rs9290929 and rs17501010) and the FLG null mutations
      R501X and 2282del4. RESULTS: In individuals without ear piercings, a higher
      prevalence of nickel sensitization was found in those with the minor allele of
      CLDN1 SNP rs9290927 (P(trend)=0.013). For CLDN1 rs17501010, contact sensitization
      to organic compounds was associated with the major allele (P(trend)=0.031). The
      risk pattern was also identified for self-reported nickel dermatitis
      (P(trend)=0.011). The fragrance sensitization prevalence differed in a pairwise
      comparison of the CLDN1 rs893051 SNP genotypes (P=0.022), with the minor allele
      being associated with a higher prevalence. The associations were confirmed in
      logistic regression analyses. CONCLUSIONS: The CLDN1 polymorphisms rs9290927,
      rs893051 and rs17501010 were associated, respectively, with nickel contact
      sensitization in individuals without ear piercings, contact sensitization to
      fragrances, and with both organic compounds and nickel contact dermatitis. We
      could not find associations between GST gene polymorphisms and contact
      sensitization. FLG mutations did not affect the observed associations.

PMID- 23136957
TI  - Luminescent properties of metal-organic framework MOF-5: relativistic time
      dependent density functional theory investigations.
AB  - The electronically excited state and luminescence property of metal-organic
      framework MOF-5 were investigated using relativistic density functional theory
      (DFT) and time-dependent DFT (TDDFT). The geometry, IR spectra, and UV-vis
      spectra of MOF-5 in the ground state were calculated using relativistic DFT,
      leading to good agreement between the experimental and theoretical results. The
      frontier molecular orbitals and electronic configuration indicated that the
      luminescence mechanism in MOF-5 follows ligand-to-ligand charge transfer (LLCT),
      namely, pi* -> pi, rather than emission with the ZnO quantum dot (QD) proposed by
      Bordiga et al. The geometry and IR spectra of MOF-5 in the electronically excited
      state have been calculated using the relativistic TDDFT and compared with those
      for the ground state. The comparison reveals that the Zn4O13 QD is rigid, whereas
      the ligands BDC(2-) are nonrigid. In addition, the calculated emission band of
      MOF-5 is in good agreement with the experimental result and is similar to that of
      the ligand H2BDC. The combined results confirmed that the luminescence mechanism
      for MOF-5 should be LLCT with little mixing of the ligand-to-metal charge
      transfer. The reason for the MOF-5 luminescence is explained by the excellent
      coplanarity between the six-membered ring consisting of zinc, oxygen, carbon, and
      the benzene ring. 

PMID- 23136958
TI  - Improving understanding of clinical trial procedures among low literacy
      populations: an intervention within a microbicide trial in Malawi.
AB  - BACKGROUND: The intervention reported in this paper was a follow up to an
      empirical study conducted in Malawi with the aim of assessing trial participants'
      understanding of randomisation, double-blinding and placebo use. In the empirical
      study, the majority of respondents (61.1%; n=124) obtained low scores (lower than
      75%) on understanding of all three concepts under study. Based on these findings,
      an intervention based on a narrative which included all three concepts and their
      personal implications was designed. The narrative used daily examples from the
      field of Agriculture because Malawi has an agro-based economy. METHODS: The
      intervention was tested using a sample of 36 women who had been identified as low
      scorers during the empirical study. The 36 low scorers were randomly assigned to
      control (n=18) and intervention arms (n=18). The control arm went through a
      session in which they were provided with standard informed consent information
      for the microbicide trial. The intervention arm went through a session in which
      they were provided with a narrative in ChiChewa, the local language, with the
      assistance of a power point presentation which included pictures as well as
      discussions on justification and personal implications of the concepts under
      study. RESULTS: The findings on the efficacy of the intervention suggest that the
      3 scientific concepts and their personal implications can be understood by low
      literacy populations using simple language and everyday local examples. The
      findings also suggest that the intervention positively impacted on understanding
      of trial procedures under study, as 13 of the 18 women in the intervention arm,
      obtained high scores (above 75%) during the post intervention assessment and none
      of the 18 in the control arm obtained a high score. Using Fischer's exact test,
      it was confirmed that the effect of the intervention on understanding of the
      three procedures was statistically significant (p=0.0001). CONCLUSIONS: Potential
      trial participants can be assisted to understand key clinical trial procedures,
      their justification and personal implications by using innovative tailored local
      narratives.

PMID- 23136959
TI  - Impact of adjusting for the reciprocal relationship between maternal weight and
      free thyroxine during early pregnancy.
AB  - BACKGROUND: Among euthyroid pregnant women in a large clinical trial, free
      thyroxine (FT4) measurements below the 2.5th centile were associated with a 17 lb
      higher weight (2.9 kg/m(2)) than in the overall study population. We explore this
      relationship further. METHODS: Among 9351 women with second trimester thyrotropin
      (TSH) measurements between 1st and 98th centiles, we examine: (i) the weight/FT4
      relationship; (ii) percentages of women in three weight categories at each FT4
      decile; (iii) FT4 concentrations in three weight categories at each TSH decile;
      and (iv) impact of adjusting FT4 for weight--in the reference group and in 190
      additional women with elevated TSH measurements. RESULTS: FT4 values decrease
      steadily as weight increases (p<0.0001 by ANOVA) among women in the reference
      group (TSH 0.05-3.8 IU/L). TSH follows no consistent pattern with weight. When
      stratified into weight tertiles, 48% of women at the lowest FT4 decile are heavy;
      the percentage decreases steadily to 22% at the highest FT4 decile. Median FT4 is
      lowest in heaviest women regardless of the TSH level. In the reference group,
      weight adjustment reduces overall variance by 2.9%. Fewer FT4 measurements are at
      either extreme (below the 5th FT4 centile: 4.8% before adjustment, 4.7% after
      adjustment; above the 95th FT4 centile: 5.0% and 4.7%, respectively). Adjustment
      places more light weight women and fewer heavy women below the 5th FT4 centile;
      the converse above the 95th centile. Between TSH 3.8 and 5 IU/L, the FT4
      percentage below the 5th FT4 centile is not elevated (3.8% before adjustment,
      3.1% after adjustment). Percentage of FT4 values above the 95th centile, however,
      is lower (1.5% before adjustment, 0.8% after adjustment). Above TSH 5 IU/L, 25%
      of women have FT4 values below the 5th FT4 centile; weight adjustment raises this
      to 30%; no FT4 values remain above the 95th FT4 centile. CONCLUSIONS: During
      early pregnancy, TSH values are not associated with weight, unlike nonpregnant
      adults. Lower average FT4 values among heavy women at all TSH deciles partially
      explain interindividual differences in FT4 reference ranges. The continuous
      reciprocal relationship between weight and FT4 explains lower FT4 with higher
      weight. Weight adjustment refines FT4 interpretation.

PMID- 23136960
TI  - Malaria and related outcomes in patients with intestinal helminths: a cross
      sectional study.
AB  - BACKGROUND: The effects of helminth co-infection on malaria in humans remain
      uncertain. This study aimed to evaluate the nature of association of intestinal
      helminths with prevalence and clinical outcomes of Plasmodium infection. METHODS:
      A cross-sectional study involving 1,065 malaria suspected febrile patients was
      conducted at Dore Bafeno Health Center, Southern Ethiopia, from December 2010 to
      February 2011. Plasmodium and intestinal helminth infections were diagnosed using
      Giemsa-stained blood films and Kato-Katz technique, respectively. Haemoglobin
      level was determined using a haemocue machine. RESULTS: Among 1,065 malaria
      suspected febrile patients, 28.8% were positive for Plasmodium parasites (P.
      falciparum =13.0%, P. vivax =14.5%, P. falciparum and P. vivax =1.3%). Among 702
      patients who provided stool samples, 53.8%, 31.6% and 19.4% were infected with
      intestinal helminths, Plasmodium alone and with both Plasmodium and intestinal
      helminths, respectively. The prevalence of infections with Ascaris lumbricoides
      (A. lumbricoides), Trichuris trichiura (T. trichiura), Schistosoma mansoni (S.
      mansoni) and hookworm (9.8%) were 35.9%, 15.8%, 11.7% and 9.8%, respectively. Out
      of the 222 (31.6%) Plasmodium infected cases, 9 (4.1%) had severe malaria. P.
      falciparum infection was more common in febrile patients infected with A.
      lumbricoides alone (21.3%), T. trichiura alone (23.1%) and S. mansoni alone
      (23.1%) compared to those without intestinal helminth infections (9.3%) (p<0.001
      for all). Prevalence of non-severe malaria was significantly higher in
      individuals infected with intestinal helminths than in those who were not
      infected with intestinal helminths (adjusted OR=1.58, 95% CI=1.13-2.22). The
      chance of developing non-severe P. falciparum malaria were 2.6, 2.8 and 3.3 times
      higher in individuals infected with A. lumbricoides alone, T. trichiura alone and
      S. mansoni alone, respectively, compared to intestinal helminth-free individuals
      (p<0.05 for all). The odds ratio for being infected with non-severe P. falciparum
      increased with the number of intestinal helminth species (p<0.001). Mean
      Plasmodium density among intestinal helminth infected individuals was
      significantly increased with the number of intestinal helminths species
      (p=0.027). Individuals who were co-infected with different species of intestinal
      helminths and Plasmodium showed lower mean haemoglobin concentration than
      individuals who were infected only with Plasmodium. CONCLUSIONS: Infections with
      A. lumbricoides, T. trichiura and S. mansoni were positively associated with P.
      falciparum infection. However, further studies are required to investigate how
      these helminths could contribute to increased prevalence of P. falciparum
      infection.

PMID- 23136961
TI  - Verification of monoplex and multiplex linear-after-the-exponential PCR gene
      specific sepsis assays using clinical isolates.
AB  - AIMS: To verify monoplex and multiplex gene-specific linear-after-the-exponential
      polymerase chain reaction (LATE-PCR) assays for identifying 17 microbial
      pathogens (i.e., Klebsiella sp., Acinetobacter baumannii, Staphylococcus aureus,
      Enterobacter sp., Pseudomonas aeruginosa, coagulase negative staphylococci,
      Enterococcus sp., Candida sp.) commonly associated with septicaemia using
      clinical isolates. METHODS AND RESULTS: Clinical isolates of each target pathogen
      were collected from the University of California, Davis Medical Center (UCDMC)
      microbiology laboratory. Five microlitres (MUl) of each culture suspension (1 *
      10(8) CFU ml(-1) ) were added to 20 MUl of monoplex mastermix. DNA extracted from
      clinical isolates was tested in multiplex. Monoplex assays demonstrated 100%
      sensitivity at this input level, except Enterobacter cloacae (2.7%), Ac.
      baumannii (57%) and Ps. aeruginosa (97.8%). All clinical isolates were positive
      in multiplex, with the exception of two Ac. baumannii, two Klebsiella oxytoca and
      two Candida parapsilosis isolates. CONCLUSIONS: Sixteen pathogens can be
      identified by monoplex LATE-PCR assays with sensitivities >= 97.8%. The multiplex
      assay demonstrated 91.4% sensitivity when tested with DNA extracted from 70
      different target strains. SIGNIFICANCE AND IMPACT OF THE STUDY: This study
      demonstrates the potential of LATE-PCR to serve as an adjunct to culture if the
      reagents are optimized for sensitivity. Results warrant further testing through
      analytical and clinical validation of the multiplex assay.

PMID- 23136962
TI  - 'Professor Galveston' has departed. Obituary--Daniel Traber.

PMID- 23136963
TI  - Overexpression of chemokine ligand 7 is associated with the progression of canine
      transmissible venereal tumor.
AB  - BACKGROUND: Chemokines play multiple roles in the development and progression in
      a variety of tumors. Chemokine (C-X-C motif) ligand 7 (CXCL7) has been found
      associated with pro-inflammatory responses, but its role in cancer growth remains
      unclear. Our previous study showed that R phase tumor infiltrating lymphocytes
      (TILs) produced large amounts of interleukin (IL)-6 which antagonized
      transforming growth factor (TGF)-beta derived from CTVT to diminish the immune
      suppressive microenvironment. Now we intend to determine the expression pattern
      of CXCL7 and the role of IL-6/TGF-beta in CXCL7 induction during spontaneous
      progressive (P) and regressive (R) phases in canine transmissible venereal tumor
      (CTVT). RESULTS: We have demonstrated that CXCL7 expressed at high level in P
      phase and down-regulated in R phase by western blot and real-time PCR. This
      suggested that CXCL7 expression was negatively correlated with the tumor growth.
      Co-culturing TILs with CTVT cells was found to reduce CXCL7 expression, while
      adding IL-6 blocking antibody reversed it. Moreover, in P phase CTVT, while IL
      1beta and TGF-beta had no obvious effect on CXCL7 expression, IL-6 was found
      significantly to reduce CXCL7 expression in a dose-dependent manner. The mRNA
      expression results of CXCL7 receptor, CXCR2, further confirmed the effects of IL
      6 concentration on the CXCL7 expression. CONCLUSION: CXCL7 overexpression might
      be associated with the progressive growth of CTVT. The results shown here also
      suggest the role of CXCL7 in cancer development and the potential as the anti
      cancer therapeutic target.

PMID- 23136964
TI  - Using nanoscale substrate curvature to control the dimerization of a surface
      bound protein.
AB  - The influence of surface geometry on adsorbed proteins offers new possibilities
      for controlling quaternary structure by manipulating protein-protein interactions
      at a surface, with applications that are relevant to protein aggregation,
      fibrillation, ligand binding, and surface catalysis. To understand the effect of
      surface curvature on the structure of the surface-bound protein beta
      lactoglobulin (beta-LG), we have used a combination of polystyrene (PS)
      nanoparticles (NPs) and ultrathin PS films to fabricate chemically pure,
      hydrophobic surfaces that have nanoscale curvature and are stable in aqueous
      buffer. We have used single molecule force spectroscopy to measure the detachment
      contour lengths L(c) for beta-LG adsorbed on the highly curved PS surfaces, and
      we compare these values in situ to those measured for beta-LG adsorbed on flat PS
      surfaces on the same samples. The L(c) distributions measured on all flat PS
      surfaces show a large monomer peak near 60 nm and a smaller dimer peak at 120 nm.
      For 190 and 100 nm diameter NPs, which are effectively flat on the scale of the
      beta-LG molecules, there is no measurable difference between the L(c)
      distributions obtained for the flat and curved surfaces. However, for 60 nm
      diameter NPs the dimer peak is smaller, and for 25 nm diameter NPs the dimer peak
      is absent, indicating that the number of surface-bound dimers is significantly
      reduced by an increase in the curvature of the underlying surface. These results
      indicate that surface curvature provides a new method of manipulating protein
      protein interactions and controlling the quaternary structure of adsorbed
      proteins.

PMID- 23136965
TI  - Cerebrospinal fluid levels of vascular endothelial growth factor correlate with
      reported pain and are reduced by spinal cord stimulation in patients with failed
      back surgery syndrome.
AB  - OBJECTIVES: Spinal cord stimulation (SCS) is an efficacious therapy for chronic
      neuropathic pain whose precise mechanism of action is unclear. Mediators produced
      by glial and immune cells are now believed to modulate neuronal transmission and
      promote chronic neuropathic pain. We postulated a relationship between
      cerebrospinal fluid (CSF) concentrations of neuroimmune mediators and SCS.
      MATERIALS AND METHODS: We measured CSF concentrations of the chemokine, monocyte
      chemotactic protein-1 (MCP-1), and the growth factors, brain-derived neurotrophic
      factor (BDNF), and vascular endothelial growth factor (VEGF) and tested for
      relationships with stimulation parameters and clinical response in nine patients
      with failed back surgery syndrome (FBSS). RESULTS: Patients with FBSS had higher
      CSF concentrations of BDNF (p = 0.01) and MCP-1 (p = 0.0001) than matched
      controls. CSF concentrations of BDNF and VEGF correlated with reported pain (p =
      0.04). Five minutes of SCS resulted in a reduction in median VEGF concentrations
      (p = 0.01). CONCLUSIONS: Patients with FBSS have altered CSF levels of BDNF and
      MCP-1. CSF VEGF correlates with pain and is reduced by SCS. This may offer novel
      insights into both the mechanism of action of SCS in FBSS and the variation in
      clinical response that may be encountered.

PMID- 23136966
TI  - Otolaryngologic challenges in cleft/craniofacial care.
AB  - An otolaryngology evaluation is an important aspect of care for any patient with
      craniofacial conditions. Otolaryngologists are commonly involved in the care of
      these patients to treat chronic otitis media, which frequently requires placement
      of pressure equalization tubes; however, there are many other
      otorhinolaryngologic issues that are addressed. Patients with craniofacial
      conditions may struggle with nasal obstruction, airway compromise, obstructive
      sleep apnea, dysphonia, swallowing, chronic sinonasal disease, and otologic
      disease. 

PMID- 23136967
TI  - Impaired response to hypoxia in the respiratory center is a major cause of
      neonatal death of the PACAP-knockout mouse.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide
      expressed widely in nervous tissues. PACAP-knockout ((-/-)) mice display a sudden
      infant death syndrome (SIDS)-like phenotype, although the underlying
      physiological mechanism to explain this remains unclear. Here, we report on the
      presence of abnormal respiratory activity in PACAP(-/-) mice under hypoxic
      conditions, which provides a basis for the SIDS-like phenotype. PACAP(-/-) mice
      display a lowered baseline respiratory activity compared with wild-type animals,
      and an abnormal response to hypoxia. More specifically, PACAP(-/-) mice at
      postnatal day 7 showed respiratory arrest in response to hypoxia. In contrast,
      their response to hypercapnic conditions was the same as that of wild-type mice.
      Histological and real-time PCR analyses indicated that the catecholaminergic
      system in the medulla oblongata was impaired in PACAP(-/-) mice, suggesting that
      endogenous PACAP affects respiratory centers in the medulla oblongata via its
      action on the catecholaminergic system. We propose that disruption of this system
      is involved in the SIDS-like phenotype of PACAP(-/-) mice. Thus, disorders of the
      catecholaminergic system involved with O(2) sensing could be implicated in
      underlying neuronal mechanisms responsible for SIDS.

PMID- 23136968
TI  - Polyphenolic and vitamin C contents and antioxidant activities of aqueous
      extracts from mature-green and ripe fruit fleshes of Mangifera sp.
AB  - Mature-green and ripe fleshes from 12 samples of  Mangifera  were selected for
      this study. The mature-green fleshes were found to have higher vitamin C contents
      than the ripe fleshes. However, not all higher total or individual phenolic
      contents were measured from the mature-green fleshes. The highest contents of
      vitamin C and total phenolics were respectively measured from the aqueous
      extracts of mature-green (255.86 +/- 12.98 MUg AAE/g sample) and ripe (142.57 +/-
      0.38 MUg GAE/g sample) fleshes of  M. petandra  cv. Pauh. Gallic acid and
      mangiferin were detected in all aqueous extracts. The extracts of the mature
      green flesh of  M. indica  cv. Chokanan and the ripe flesh of M. indica cv. Siku
      Raja, respectively, exhibited the greatest 1,1-diphenyl-2-picrylhydrazyl radical
      (DPPH)-scavenging activity (408.21 +/- 5.37 MUg TE/g sample) and metal chelating
      activity (93.68 +/- 0.74%). The combined or potentiation effects of the moderate
      vitamin C, gallic acid, and mangiferin contents in both extracts may be
      responsible for the activities. The highest mangiferin content (31.72 +/- 2.57
      MUg/g sample) in the mature-green  M. caesia  (Binjai) could be the major
      contributor to its highest FRAP activity (868.29 +/- 2.71 MUg TE/g sample). This
      paper reports apparently the first comparative study highlighting the antioxidant
      activities of these fruit fleshes.

PMID- 23136970
TI  - 5-Hydroxyindoles by intramolecular alkynol-furan diels-alder cycloaddition.
AB  - A convergent approach provides a convenient access to synthetically and
      biologically useful 3,4-disubstituted 5-hydroxyindoles. The one-pot procedure
      uses microwave heating to initiate an intramolecular [4 + 2]-cycloaddition of an
      alkynol segment onto a furan followed by a fragmentation, aromatization, and N
      Boc deprotection cascade. Yields range from 15 to 74%, with aromatic substituents
      providing better conversions. 4-Trimethylsilylated analogues undergo a 1,3
      silatropic rearrangement to give the O-TMS ethers.

PMID- 23136969
TI  - Activation of de novo GSH synthesis pathway in mouse spleen after long term low
      dose gamma-ray irradiation.
AB  - Glutathione (GSH) is an important cellular antioxidant and has a critical role in
      maintaining the balance of cellular redox. In this study, we investigated the GSH
      biosynthesis genes involved in the elevation of endogenous GSH levels using an
      irradiation system with an irradiation dose rate of 1.78 mGy/h, which was about
      40,000 times less than the dose rates used in other studies. The results showed
      that GSH levels were significantly increased in the low-dose (0.02 and 0.2 Gy)
      irradiated group compared to those in the non-irradiated group, but enzymatic
      antioxidants such as superoxide dismutase and catalase were not induced at any
      doses tested. The elevation in GSH was accompanied by elevated expression of
      glutamate-cysteine ligase modifier subunit, but no changes were observed in the
      expression of glutamate-cysteine ligase catalytic subunit and thioredoxin in de
      novo GSH synthesis. In the case of genes involved in the GSH regeneration cycle,
      the expression of glutathione reductase was not changed after irradiation,
      whereas glutathione peroxidase was only increased in the 0.2 Gy irradiated group.
      Collectively, our results suggest that the de novo pathway, rather than the
      regeneration cycle, may be mainly switched on in response to stimulation with
      long-term low-dose radiation in the spleen.

PMID- 23136971
TI  - Functional analysis of Aoatg1 and detection of the Cvt pathway in Aspergillus
      oryzae.
AB  - Autophagy is a degradation system in which cellular components are digested via
      vacuoles/lysosomes. In the budding yeast Saccharomyces cerevisiae, the induction
      of autophagy results from inactivation of target of rapamycin complex 1 (TORC1),
      promoting formation of the serine/threonine kinase Atg1, which is one of the key
      autophagy-related (Atg) proteins required for both nonselective and selective
      autophagy such as the cytoplasm-to-vacuole targeting (Cvt) pathway. Here, to
      understand the induction mechanism of autophagy in filamentous fungi, we first
      identified the ATG1 homolog Aoatg1 in Aspergillus oryzae and then analyzed the
      localization of an enhanced green fluorescent protein (EGFP)-AoAtg1 fusion
      protein. AoAtg1-EGFP localized to pre-autophagosomal structure (PAS)-like
      structures, similar to Atg1 localization in S. cerevisiae. The function of AoAtg1
      was evaluated by constructing an Aoatg1 disruptant, DeltaAoatg1. Conidiation and
      development of aerial hyphae were scarcely observed in DeltaAoatg1. Moreover,
      autophagy in the disruptant was examined by observation of the localization of
      EGFP-AoAtg8 and AoApe1-EGFP, with the results indicating that AoAtg1 is essential
      for nonselective autophagy and the Cvt pathway. Furthermore, we demonstrated that
      the overexpression of Aoatg1 results in decreased conidiation and the excessive
      development of aerial hyphae and sclerotia. Taken together, our findings provide
      evidence for the existence of the Cvt pathway in A. oryzae.

PMID- 23136972
TI  - D-amino acids boost the selectivity and confer supramolecular hydrogels of a
      nonsteroidal anti-inflammatory drug (NSAID).
AB  - As systemically used therapeutics for treating acute or chronic pains or
      inflammations, nonsteroidal anti-inflammatory drugs (NSAIDs) also associate with
      the adverse gastrointestinal and renal effects and cardiovascular risks. Thus, it
      is beneficial to develop topical gels that selectively inhibit cyclooxygenase-2
      (COX-2) for the management of local inflammation. In this work, we demonstrate
      that the covalent conjugation of d-amino acids to naproxen (i.e., a NSAID) not
      only affords supramolecular hydrogelators for the topical gels but also
      unexpectedly and significantly elevates the selectivity toward COX-2 about 20* at
      little expense of the activity of naproxen. This work illustrates a previously
      unexplored approach that employs d-amino acids for the development of functional
      molecules that have dual or multiple roles and exceptional biostability, which
      offers a new class of molecular hydrogels of therapeutic agents.

PMID- 23136973
TI  - Translocations in spleen cells from adult mice irradiated as fetuses are
      infrequent, but often clonal in nature.
AB  - We previously reported that mouse fetuses or neonates exposed to 2 Gy of X rays
      showed an unexpectedly low incidence of chromosome damage in lymphocytes, bone
      marrow, and spleen cells when the mice were subsequently examined at 20 weeks of
      age. However, cells bearing translocations were occasionally observed that, on
      the basis of 2-color whole chromosome painting appeared to be clonal descendants.
      Unfortunately, this approach typically did not permit unequivocal confirmation of
      their clonality. To overcome this problem, multi-color FISH (mFISH) was employed,
      which assigns all 21 individual chromosome types of the mouse a unique color.
      After mFISH analyses of the same cell samples studied previously, it was
      confirmed that spleen cells of 20-week-old mice irradiated either as 15.5-day
      fetuses or as 3- to 4-day-old neonates showed translocation frequencies close to
      zero. Translocations previously suspected as being clonal in nature were
      confirmed as such by mFISH, which also revealed the presence of an additional
      clone not previously detected or suspected. Since no evidence of clonality was
      observed in the irradiated mother, we concluded that in both fetuses and
      neonates, there exists a small fraction of stem cells that are distinct from the
      bulk of the stem cell compartment in terms of their ability to acquire and
      transmit radiation-induced chromosome damage through clonal expansion.

PMID- 23136974
TI  - Orally administered liposomal lactoferrin inhibits inflammation-related bone
      breakdown without interrupting orthodontic tooth movement.
AB  - BACKGROUND: Bovine lactoferrin (bLF) modulates the production of tumor necrosis
      factor-alpha (TNF-alpha) and inhibits alveolar bone breakdown associated with
      periodontitis. This study is designed to examine the effects of orally
      administered liposomal bLF (LbLF) on orthodontic force (OF)-induced alveolar bone
      remodeling during experimental tooth movement. METHODS: Two groups of male Wistar
      rats were treated with either LbLF or control solution in drinking water 7 days
      before OF application. Lipopolysaccharide (LPS) was injected into the gingival
      sulcus in half the rats in each group. Thus, four groups: OF, OF+LbLF, OF+LPS,
      and OF+LPS+LbLF were established. RESULTS: Orally administered LbLF significantly
      reduced apical migration of junctional epithelium in the OF and OF+LPS groups. In
      OF+LPS, osteoclast number in the alveolar crestal area was increased by LPS
      treatment, whereas osteoclast number was significantly reduced in OF+LPS+LbLF
      through suppression of TNF-alpha production. Osteoclastic induction in the middle
      part, mainly from OF application, was not affected by LbLF administration.
      Inhibition of tooth movement was not induced by LbLF. CONCLUSIONS: Orally
      administered LbLF significantly inhibits LPS-induced alveolar bone resorption but
      not OF-induced bone remodeling. LbLF could be a potent therapeutic and preventive
      agent to control periodontal inflammation in patients undergoing orthodontic
      treatment.

PMID- 23136975
TI  - BK virus replication and nephropathy after alemtuzumab-induced kidney
      transplantation.
AB  - BK virus nephropathy (BKVN) is a recognized cause of graft failure in kidney
      transplant recipients. There are limited data on the epidemiology of BK virus
      (BKV) infection after alemtuzumab induction. By clinical protocol, the kidney
      transplant recipients at our center were screened with BKV plasma PCR monthly for
      the first 4 months posttransplant then every 2-3 months for 2 years. A single
      center retrospective cohort study of all kidney transplant recipients from
      January 2008 to August 2010 was conducted to determine incidence and outcomes of
      BKV infection. Descriptive statistics and Kaplan-Meier analysis was performed. Of
      666 recipients, 250 (37.5%) developed viruria, 80 (12%) developed viremia and 31
      (4.7%) developed BKVN at a median of 17, 21 and 30 weeks, respectively. Induction
      with alemtuzumab did not significantly affect incidence of BKVN. Increased
      recipient age, African American race, acute graft rejection and CMV infection
      were significantly associated with the development of BKVN in multivariate
      analysis. The incidence of BK viruria, viremia and nephropathy was not
      significantly different among kidney transplant recipients who received
      alemtuzumab induction compared to patients receiving less potent induction.

PMID- 23136976
TI  - Computational insights on the isomerization of photochromic oxazines.
AB  - We investigated the isomerization of the simplest member of a family of
      photochromic oxazines with the aid of density functional theory, using three
      different functionals. Specifically, we simulated the thermal interconversion of
      the two enantiomers, associated with this compound, and established that the
      opening of the oxazine ring dictates the rate of the overall degenerate process.
      The M062X functional provides the best match to experimental data, whereas B3LYP
      calculations fail to model accurately the ground-state potential-energy surface
      of this system. In addition, we also modeled the absorption spectra of this
      compound and its photogenerated isomer with time-dependent calculations. The
      resulting data support the original assignment of the experimental spectra and
      confirm that the oxazine ring opens upon excitation. The MPW1PW91 functional
      provides the best match to experimental data, whereas M062X calculations fail to
      model accurately the spectroscopic parameters of this particular system.
      Furthermore, the MPW1PW91 calculations demonstrate that the photoinduced opening
      of the oxazine ring occurs along the potential-energy surface of the first
      triplet excited state. Indeed, the photoinduced isomerization appears to involve:
      (1) the initial excitation of one isomer to the second singlet excited state, (2)
      its thermal relaxation to the first triplet excited state, (3) its ring opening
      to produce the other isomer, and (4) the thermal relaxation of the product to the
      ground state. Thus, our calculations provide valuable information on the
      elementary steps governing the isomerization of this particular photochromic
      compound in the ground state and upon excitation. These useful mechanistic
      insights can guide the design of novel members of this family of photoresponsive
      compounds with specific properties.

PMID- 23136977
TI  - Trends of influenza infection in Suriname.
AB  - The trends of influenza infection in Suriname were assessed from February 2010
      through February 2011. Testing of 393 patients with symptoms of acute respiratory
      infection (ARI) revealed 15.3% Influenza B and 18.6% could be identified as
      influenza A positive, consisting of 56% influenza A(H1N1)pdm09 and 44% seasonal
      A(H3N2). Influenza infection occurred throughout the year, and all three
      influenza types affected young children as the primary population. The annual
      incidence of A(H1N1)pdm09 was 6.88 per 100,000 inhabitants [CI] 4.87-9.45. The
      spread of influenza could neither be linked to tourist flow from the Netherlands
      nor to contact rates related to school schedules.

PMID- 23136978
TI  - Systematic safety review and meta-analysis of procedural experience using
      percutaneous access to treat symptomatic lumbar spinal stenosis.
AB  - OBJECTIVE: This systematic safety review reports multicenter safety results of
      symptomatic lumbar spinal stenosis (LSS) patients treated with percutaneous
      lumbar decompression. DESIGN: All percutaneous lumbar decompression institutional
      review board-approved study patients, as well as a retrospective safety survey,
      were included in this review. METHODS: All study centers followed the same widely
      accepted and standardized procedure for percutaneous decompression and utilized
      the same criteria when observing and reporting device- or procedure-related
      adverse events. OUTCOME MEASURES: In addition to safety data, Oswestry Disability
      Index scores were used to document baseline functional disability, and visual
      analog scale values defined the intensity of baseline back and leg pain.
      Treatment outcomes of patients who reached 1-year follow-up were also included.
      RESULTS: Of the 373 patients included in this safety review, there were no
      reports of major device- or procedure-related adverse events, and there were no
      mortalities. Major complications were defined as any device- or procedure-related
      event that required intervention, including events such as incidental durotomy,
      epidural hematoma, infection, or bleeding that required transfusion. One-year
      efficacy data showed statistically significant improvement in pain and mobility,
      further supporting the excellent safety profile of percutaneous lumbar
      decompression. CONCLUSIONS: In this safety review, percutaneous lumbar
      decompression proved to be a safe procedure. Compared with other more invasive
      lumbar decompression techniques, percutaneous lumbar decompression has
      demonstrated significantly better safety. This high level of safety is
      particularly vital for the rapidly growing elderly LSS patient population with
      increased treatment risks related to comorbid medical issues.

PMID- 23136979
TI  - A nine-coordinated bismuth(III) complex derived from pentadentate 2,6
      diacetylpyridine bis((4)N-methylthiosemicarbazone): crystal structure and both in
      vitro and in vivo biological evaluation.
AB  - Up to now, bismuth(III) complexes with thiosemicarbazones have been comparatively
      rare. Few in vivo biological studies have been carried out in comparison to the
      plentiful in vitro data. Here, an interesting nine-coordinated bismuth(III)
      complex, [Bi(H2L)(NO3)2]NO3 [1; H2L = 2,6-diacetylpyridine bis((4)N
      methylthiosemicarbazone)], has been synthesized and structurally characterized.
      The analytical data reveal the formation of 1:1 (metal/ligand) stoichiometry. In
      vitro biological studies have indicated that the bismuth complex 1 has shown much
      higher antibacterial and anticancer activities than its parent ligand, especially
      with MIC = 10.66 MUM against Bacillus cereus and Salmonella typhimurium and IC50
      = 26.8 MUM against K562 leukemia cells, respectively. More importantly, it also
      evidently inhibits H22 xenograft tumor growth on tumor-bearing mice (10 mg/kg;
      inhibitory rate = 61.6%). These results indicate that coordination to
      bismuth(III) might be an interesting strategy in the discovery of new anticancer
      drug candidates. 

PMID- 23136980
TI  - Association of specific pectin methylesterases with Al-induced root elongation
      inhibition in rice.
AB  - The negative charges of cell wall pectin molecules attributed by pectin
      methylesterase (PME, EC 3.1.1.11) contribute to Al binding capacity. We examined
      the expression profiles of 35 members of the PME gene family in the root apex of
      an Al-sensitive rice 'Zhefu802' under Al stress. While root elongation was
      inhibited by 40% after 3-h exposure to 25 uM Al, cell wall PME activity and the
      abundance of eight PME genes transcripts were increased. The same Al treatment
      which had almost no effect on root elongation of an Al-resistant rice ssp.
      japonica 'Nipponbare' did not change the expression patterns of these eight PME
      genes. However, when Al concentration was increased to 50 uM, by which the root
      elongation of 'Nipponbare' was inhibited by 40% too, the expression of these PME
      genes were also upregulated except two genes with no signal. These suggest a
      possible correlation between the upregulated genes and Al-induced inhibition of
      root elongation in rice. Furthermore, these eight PME genes behaved differently
      when subjected to CdCl2 and LaCl3 treatments, implying the specificity of
      different PME genes in response to different metal toxicities. The transgenic
      rice overexpressing one of these eight PME genes OsPME14 showed higher PME
      activity and Al content in root tip cell wall, and became more sensitive to Al
      stress, verifying the involvement of the specific PME gene in Al toxicity.
      Therefore, our results provided the molecular evidence to connect the expression
      of specific PME genes with the Al-induced inhibition of root elongation in rice. 

PMID- 23136981
TI  - Operationalization of three dimensions of sexual orientation in a national survey
      of late adolescents.
AB  - This study investigated three dimensions of sexual orientation-identity,
      attraction, and behavior-in a national survey of late adolescents. Prevalence
      rates and the diversity of dimensions of sexual orientation when combined were
      studied. A representative sample of 3,432 Swedish high school seniors completed
      an anonymous school-based self-report survey about sexuality, Internet use, and
      health. Four measures of sexual orientation were included-one for sexual
      identity, two for attraction (emotional or sexual attraction, romantic
      attraction), and one for sexual behavior. Prevalence rates of sexual minority
      orientation varied between 4.3% for sexual behavior (males 2.9%, females 5.6%)
      and 29.4% for emotional or sexual attraction (males 17.7%, females 39.5%).
      Different measures of sexual orientation were significantly associated with one
      another. Bisexual or homosexual orientation was reported by 1.5% of the
      participants in all four measures and by 17.6% in at least one measure.
      Researchers need to carefully choose, depending on the research questions under
      investigation, which dimensions of sexual orientation and which measures they
      wish to include in their survey. Recommendations based on findings from the study
      are given. 

PMID- 23136983
TI  - Quantitative measurement of the surface self-diffusion on Au nanoparticles by
      aberration-corrected transmission electron microscopy.
AB  - We present a method that allows for a quantitative measurement of the surface
      self-diffusion on nanostructures, such as nanoparticles, at the atomic scale
      using aberration-corrected high-resolution transmission electron microscopy
      (HRTEM). The diffusion coefficient can be estimated by measuring the fluctuation
      of the atom column occupation at the surface of Au nanoparticles, which is
      directly observable in temporal sequences of HRTEM images. Both a Au icosahedron
      and a truncated Au octahedron are investigated, and their diffusion coefficients
      are found to be in the same order of magnitude, D = 10(-17) to 10(-16) cm(2)/s.
      It is to be assumed that the measured surface diffusion is affected by the
      imaging electron beam. This assumption is supported by the observed instability
      of a (5 * 1) surface reconstruction on a {100} Au facet.

PMID- 23136982
TI  - Oesophagectomy rates and post-resection outcomes in patients with cancer of the
      oesophagus and gastro-oesophageal junction: a population-based study using linked
      health administrative linked data.
AB  - BACKGROUND: Hospital performance is being benchmarked increasingly against
      surgical indicators such as 30-day mortality, length-of-stay, survival and post
      surgery complication rates. The aim of this paper was to examine oesophagectomy
      rates and post-surgical outcomes in cancers of the oesophagus and gastro
      oesophageal junction and to determine how the addition of gastro-oesophageal
      cancer to oesophageal cancer impacts on these outcomes. METHODS: Our study
      population consisted of patients with a primary invasive oesophageal or gastro
      oesophageal cancer identified from the NSW Cancer Registry from July 2000-Dec
      2007. Their records were linked to the hospital separation data for determination
      of resection rates and post-resection outcomes. We used multivariate logistic
      regression analyses to examine factors associated with oesophagectomy and post
      resection outcomes. Cox-proportional hazard regression analysis was used to
      examine one-year cancer survival following oesophagectomy. RESULTS: We observed
      some changes in resection rates and surgical outcomes with the addition of gastro
      oesophageal cancer patients to the oesophageal cancer cohort. 14.6% of
      oesophageal cancer patients and 26.4% of gastro-oesophageal cancer patients had
      an oesophagectomy; an overall oesophagectomy rate of 18.2% in the combined
      cohort. In the combined cohort, oesophagectomy was associated with younger age,
      being male and Australian-born, having non-metastatic disease or adenocarcinoma
      and being admitted in a co-located hospital. Rates of length-of-stay >28 days
      (20.9% vs 19.7%), 30-day mortality (3.8% vs 2.7%) and one-year survival post
      surgery (24.5% vs 23.1%) were similar between oesophageal cancer alone and the
      combined cohort; whilst 30-day complication rates were 21.5% versus 17.0%
      respectively. Some factors statistically associated with post-resection
      complication in oesophageal cancer alone were not significant in the overall
      cohort. Poorer post-resection outcomes were associated with some patient (older
      age, birthplace) and hospital-related characteristics (fiscal sector, area health
      service). CONCLUSION: Outcomes following oesophagectomy in oesophageal and gastro
      oesophageal cancer patients in NSW are within world benchmarks. Our study
      demonstrates that the inclusion of gastro-oesophageal cancer did alter some
      outcomes compared to analysis based solely on oesophageal cancer. As such, care
      must be taken with analyses based on administrative health data to capture all
      populations eligible for treatment and to understand the contribution of these
      subpopulations to overall outcomes.

PMID- 23136984
TI  - Validation of IRS PCR, a molecular typing method, for the study of the diversity
      and population dynamics of Legionella in industrial cooling circuits.
AB  - Legionella bacteria are ubiquitous in aquatic environments. Members of the
      species Legionella pneumophila are responsible for more than 98% of cases of
      Legionnaires' disease in France. Our objective was to validate a molecular typing
      method called infrequent restriction site PCR (IRS PCR), applied to the study of
      the ecology of Legionella and to compare this method with reference typing
      methods, pulsed-field gel electrophoresis (PFGE) and sequence-based Typing (SBT).
      PFGE and SBT are considered as gold methods for the epidemiological typing of
      Leg. pneumophila strains. However, these methods are not suitable to an
      ecological monitoring of Legionella in natural environments where a large number
      of strains has to be typed. Validation of IRS PCR method was performed by the
      identification of 45 Leg. pneumophila isolates from cooling circuits of thermal
      power plants by IRS PCR, PFGE and SBT. The parameters of each method were
      measured and compared to evaluate the effectiveness of IRS PCR. The results of
      this study showed that IRS PCR has a discriminating power similar or better than
      that of the reference methods and thus that, by its speed and low cost represents
      an appropriate tool for the study of the ecology of Legionella in cooling
      circuits.

PMID- 23136986
TI  - Psychotherapists' self-reports of their interpersonal functioning and
      difficulties in practice as predictors of patient outcome.
AB  - The need for psychotherapy research to understand the therapist effect has been
      emphasized in several studies. In a large naturalistic study (255 patients, 70
      therapists), this topic was addressed using therapists' self-assessed
      difficulties in practice and interpersonal functioning in therapeutic work as
      predictors of patient outcome in three conventional outcome measures. Three-level
      growth curve analyses were employed to assess whether the therapist
      characteristics, measured by the Development of Psychotherapists Common Core
      Questionnaire (Orlinsky & Ronnestad, 2005), predicted the level of and change in
      patient symptom distress (SCL-90R), interpersonal problems (IIP-64), and observer
      rated global functioning (GAF). Preliminary estimates of therapist effects in
      patient change indicated that 4% of change in general symptom distress (GSI),
      almost 21% of change in IIP global scores, and 28% of growth in GAF could be
      attributed to therapist differences. The results also demonstrated that certain
      therapist self-perceptions were clearly related to patient outcome. For example,
      therapists' scores on a type of difficulty in practice called "Professional self
      doubt" (PSD) (denoting doubt about one's professional efficacy) were positively
      associated with change in IIP global scores. It is suggested that therapists'
      self-reported functioning can be of value in understanding how individual
      therapists contribute to therapeutic change although their influence is not
      necessarily exerted in expected directions.

PMID- 23136987
TI  - Physician self-reported treatment of brain metastases according to patients'
      clinical and demographic factors and physician practice setting.
AB  - BACKGROUND: Limited data guide radiotherapy choices for patients with brain
      metastases. This survey aimed to identify patient, physician, and practice
      setting variables associated with reported preferences for different treatment
      techniques. METHOD: 277 members of the American Society for Radiation Oncology
      (6% of surveyed physicians) completed a survey regarding treatment preferences
      for 21 hypothetical patients with brain metastases. Treatment choices included
      combinations of whole brain radiation therapy (WBRT), stereotactic radiosurgery
      (SRS), and surgery. Vignettes varied histology, extracranial disease status,
      Karnofsky Performance Status (KPS), presence of neurologic deficits, lesion size
      and number. Multivariate generalized estimating equation regression models were
      used to estimate odds ratios. RESULTS: For a hypothetical patient with 3 lesions
      or 8 lesions, 21% and 91% of physicians, respectively, chose WBRT alone, compared
      with 1% selecting WBRT alone for a patient with 1 lesion. 51% chose WBRT alone
      for a patient with active extracranial disease or KPS=50%. 40% chose SRS alone
      for an 80 year-old patient with 1 lesion, compared to 29% for a 55 year-old
      patient. Multivariate modeling detailed factors associated with SRS use,
      including availability of SRS within one's practice (OR 2.22, 95% CI 1.46-3.37).
      CONCLUSIONS: Poor prognostic factors, such as advanced age, poor performance
      status, or active extracranial disease, correspond with an increase in
      physicians' reported preference for using WBRT. When controlling for clinical
      factors, equipment access was independently associated with choice of SRS. The
      large variability in preferences suggests that more information about the
      relative harms and benefits of these options is needed to guide decision-making.

PMID- 23136988
TI  - Association of soluble endothelial protein C receptor plasma levels and PROCR
      rs867186 with cardiovascular risk factors and cardiovascular events in coronary
      artery disease patients: the Athero Gene study.
AB  - BACKGROUND: Blood coagulation is an essential determinant of coronary artery
      disease (CAD). Soluble Endothelial Protein C Receptor (sEPCR) may be a biomarker
      of a hypercoagulable state. We prospectively investigated the relationship
      between plasma sEPCR levels and the risk of cardiovascular events (CVE). METHODS:
      We measured baseline sEPCR levels in 1673 individuals with CAD (521 with acute
      coronary syndrome [ACS] and 1152 with stable angina pectoris [SAP]) from the
      AtheroGene cohort. During a median follow up of 3.7 years, 136 individuals had a
      CVE. In addition, 891 of these CAD patients were genotyped for the PROCR rs867186
      (Ser219Gly) variant. RESULTS: At baseline, sEPCR levels were similar in
      individuals with ACS and SAP (median: 111 vs. 115 ng/mL respectively; p=0.20).
      Increased sEPCR levels were found to be associated with several cardiovascular
      risk factors including gender (p=0.006), soluble Tissue Factor levels (p=0.0001),
      diabetes (p=0.0005), and factors reflecting impaired renal function such as
      creatinine and cystatin C (p<0.0001). sEPCR levels were not significantly
      associated with the risk of CVE (median: 110 and 114 ng/mL in individuals with
      and without future CVE respectively; p=0.68). The rs867186 variant was found to
      explain 59% of sEPCR levels variability (p<10-200) but did not associate with CVE
      risk. CONCLUSION: Our findings show that in patients with CAD, circulating sEPCR
      levels are related to classical cardiovascular risk factors and renal impairment
      but are not related to long-term incidence of CVE.

PMID- 23136989
TI  - New screening methods for probiotics with adhesion properties to sialic acid and
      sulphate residues in human colonic mucin using the Biacore assay.
AB  - AIMS: To determine the relationship between adhesive ability of probiotics and
      acidic residues in human colonic mucin, we developed a new screening method using
      Biacore to evaluate adherence of bacteria before and after sialic acid or
      sulphate residues were blocked or removed from mucin. METHODS AND RESULTS: Ten
      strains of lactobacilli and three strains of bifidobacteria isolated from human
      faeces were evaluated for their adhesive properties to soluble human colonic
      mucin (sHCM) using the Biacore binding assay. Three strains (Lactobacillus strain
      ME-522, Lact. gasseri ME-527 and Bifidobacterium bifidum MCC1092) showing
      significant adherence were selected. Decreased binding activities were observed
      after removing sialic acid of sHCM using sialidase. However, after removing the
      sulphate residue using sulphatase, the adhesion of ME-527 decreased; whereas the
      remaining two strains had increased adhesion. The adhesion of three probiotics
      significantly decreased after the sulphate residue was blocked by elution with
      barium chloride. CONCLUSIONS: A new evaluation method using the Biacore assay was
      developed to observe binding properties to the acidic residues of sHCM. Results
      indicated that there was a strong relationship between probiotic adhesion and
      acidic residues of sHCM. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first
      report showing a screening method that quantitatively measures the binding
      between bacteria and acidic residues in sHCM using the Biacore binding assay; and
      provides a new method for the selection of probiotics in the future.

PMID- 23136990
TI  - The impact of preparation parameters on typical attributes of chitosan-heparin
      nanohydrogels: particle size, loading efficiency, and drug release.
AB  - Today, developing an optimized nanoparticle (NP) preparation procedure is of
      paramount importance in all nanoparticulate drug delivery researches, leading to
      expanding more operative and clinically validated nanomedicines. In this study, a
      one-at-a-time experimental approach was used for evaluating the effect of various
      preparation factors on size, loading, and drug release of hydrogel NPs prepared
      with ionotropic gelation between heparin and chitosan. The size, loading
      efficiency (LE) and drug release profile of the NPs were evaluated when the
      chitosan molecular weight, chitosan concentration, heparin addition time to
      chitosan solution, heparin concentration, pH value of chitosan solution,
      temperature, and mixing rate were changed separately while other factors were in
      optimum condition. The results displayed that size and LE are highly influenced
      by chitosan concentration, getting an optimum of 63 +/- 0.57 and 75.19 +/- 2.65,
      respectively, when chitosan concentration was 0.75 mg/ml. Besides, heparin
      addition time of 3 min leaded to 74.1 +/- 0.79 % LE with no sensible effect on
      size and release profile. In addition, pH 5.5 showed a minimum size of 63 +/-
      1.87, maximum LE of 73.81 +/- 3.13 and the slowest drug release with 63.71 +/-
      3.84 % during one week. Although LE was not affected by temperature, size and
      release reduced to 63 +/- 0 and 74.21 +/- 1.99% when temperature increased from
      25 degrees C to 55 degrees C. Also, continuous increase of mixer rate from 500 to
      3500 rpm resulted in constant enhancement of LE from 58.3 +/- 3.6 to 74.4 +/-
      2.59 as well as remarkable decrease in size from 148 +/- 4.88 to 63 +/- 2.64.

PMID- 23136991
TI  - Impedance variations over time for a closed-loop neurostimulation device: early
      experience with chronically implanted electrodes.
AB  - OBJECTIVE: Responsive neurostimulation (RNS(r)) is an investigational treatment
      modality for intractable focal epilepsy. We analyzed impedance values over time
      to gain a better understanding of RNS device stability, potential differences
      between depth and strip electrodes, and general implications of long-term
      electrode implantation. MATERIALS AND METHODS: Impedance measurements were
      retrospectively reviewed from seven patients over a 3-year period. Statistical
      analysis was performed to investigate trends in impedance values over time and to
      determine if any differences existed between the means and variances of impedance
      values for the two different electrodes. RESULTS: Intraparenchymal depth
      electrodes demonstrated lower mean impedances and had less variation over time
      when compared to subdural strip electrodes. There was no significant change in
      mean impedance over time for depth electrodes, while that of subdural electrodes
      increased over time to peak at 16-20 months and returned to baseline by 2 years.
      CONCLUSION: The RNS device provides unique long-term data for both depth and
      subdural electrodes in human subjects. Although changes in impedance were
      observed with respect to time after implantation and electrode type, these
      variations were of a clinically insignificant magnitude. As a constant-current
      system, the device is ultimately able to administer stable therapeutic doses in
      the setting such minor variability. While further animal research and post mortem
      investigations in human subjects are necessary to broaden our understanding of
      the mechanisms occurring at the electrode-neural interface and the
      biocompatibility of chronically implanted electrodes, the relative stability of
      impedances seen in this cohort of chronic implants brings promise to future
      implementations of chronic intracranial neural implants.

PMID- 23136992
TI  - Identification of Sensory-Active Phytochemicals in Asparagus (Asparagus
      officinalis L.).
AB  - Sensory-directed fractionation of extracts prepared from raw and cooked asparagus
      (Asparagus officinalis L.), respectively, followed by LC-TOF-MS, LC-MS/MS, and
      1D/2D-NMR experiments revealed the chemical structures of nine bitter tasting
      mono- and bidesmotic saponins as well as the previously not reported 1,2
      dithiolan-4-carboxylic acid 6-D-alpha/beta-glucopyranose ester exhibiting an
      interesting buttery mouth-coating effect. Sensory studies showed that the
      orosensation imparted by this sulfur compound was reminiscent to that of melting
      butter and revealed an orosensory recognition threshold of 276.8 MUmol/L.

PMID- 23136993
TI  - Bilobar colorectal liver metastases: a new model for preclinical studies.
AB  - SUMMARY: This study aimed to develop a new model of colorectal liver metastases
      (LM) in the rat. Both single macroscopic and multiple bilobar microscopic LM were
      investigated, as this closely resembled the human situation, before right
      hepatectomy was performed for 'single' right LM. The single macroscopic LM was
      elicited by direct injection of DHD/K12 colorectal cancer cells under the capsule
      of the median liver lobe in immunocompetent BDIX rats. The bilobar
      micrometastases were elicited by intraportal injection of DHD/K12 cells. A
      preliminary protocol was conducted to assess the dose of cells required to inject
      in to the portal vein, using 10(6) , 2 * 10(6)  and 3 * 10(6)  DHD/K12 cells (n =
      15 rats). The resultant protocol for the experimental model used intraportal
      injection of 10(6)  DHD/K12 cells and direct injections of 0.5 * 10(6) , 10(6) 
      and 1.5 * 10(6)  DHD/K12 cells (n = 15 rats). For both protocols, BDIX rats were
      sacrificed at day 30 after injection. The preliminary protocol showed that
      intraportal injection of 10(6)  DHD/K12 cells was associated with bilobar
      micrometastases of 0.8 mm mean diameter at day 30. The main protocol assessed
      that direct injection of 0.5 * 10(6)  under the liver median lobe capsule and
      intraportal injection of 10(6)  DHD/K12 cells were associated at day 30 with a
      single macroscopic metastasis confined to a liver lobe and bilobar
      micrometastases, without peritoneal carcinomatosis or lung metastasis. Thus we
      have developed a new experimental model of bilobar colorectal LM including both
      macro- and microscopic colorectal LMs, which mimics the human situation and which
      will be useful in preclinical studies.

PMID- 23136994
TI  - Murine pulmonary infection and inflammation induced by inhalation of Burkholderia
      pseudomallei.
AB  - Melioidosis is a tropical disease caused by ingestion, percutaneous inoculation
      or inhalation of the Gram-negative soil saprophyte Burkholderia pseudomallei. We
      developed a reproducible experimental murine model of pneumonic melioidosis
      induced by inhalation of aerosolized B. pseudomallei 1026b. In a series of
      experiments performed to bracket the lethal dose, we found that C57BL/6 mice were
      modestly more resistant than BALB/c mice (median lethal dose 334 CFU/lung vs 204
      CFU/lung). We further characterized infection and pulmonary inflammation in
      C57BL/6 mice infected with a sublethal dose. We observed pulmonary replication
      and dissemination of bacteria to distant organs in the first days after
      infection, followed by bacterial containment by day 4 and no evidence of
      recrudescent infection for up to 2 months. We measured a robust host inflammatory
      response notable for a neutrophilic bronchoalveolar lavage fluid profile,
      elevated cytokines and chemokines in the lung and serum and scattered foci of
      neutrophilic infiltrates in the alveoli and in a perivascular distribution on
      histological analysis. We previously noted a similar pattern of inflammation in
      mice infected with aerosolized B. thailandensis. This report builds on the
      limited literature describing experimental murine pneumonic melioidosis induced
      by aerosol and characterizes pulmonary infection and resultant inflammation in
      C57BL/6 mice infected with aerosolized B. pseudomallei. This model has utility
      for the study of bacterial and host factors that contribute to the virulence of
      melioidosis.

PMID- 23136995
TI  - Chronic caffeine intake increases androgenic stimuli, epithelial cell
      proliferation and hyperplasia in rat ventral prostate.
AB  - Coffee intake has been associated with a low risk of developing cancer, including
      prostate cancer, which is one of the most commonly diagnosed cancer in men.
      However, few studies have evaluated the chronic effects of caffeine, which is the
      most abundant methylxanthine in coffee, on prostate morphology and physiology. In
      the present study, we investigated the effects of chronic, low-dose caffeine
      intake on rat prostate morphology from puberty to adulthood. Five-week-old male
      Wistar rats were randomized into two experimental groups: caffeine-treated (20
      ppm in drinking water, n = 12) and control (n = 12). The ventral and dorsolateral
      prostates were dissected, weighted and submitted to morphological, morphometrical
      and immunohistochemical analysis of cellular proliferation, apoptosis and
      androgen receptor (AR) tissue expression. The testosterone (T) and
      dihydrotestosterone (DHT) concentrations were measured in the plasma. Our results
      show that caffeine intake increased the concentrations of T and DHT, organ
      weight, epithelial cell proliferation and AR tissue expression in the ventral
      prostatic lobe. All the ventral prostates from the caffeine-treated animals
      presented various degrees of epithelial and stromal hyperplasia. Our results
      suggest that chronic caffeine intake from puberty increases androgenic signalling
      and cell proliferation in the rat prostate gland and can be related to the
      development of benign prostatic hyperplasia.

PMID- 23136996
TI  - Distribution of Zonula Occludens-1 and Occludin and alterations of testicular
      morphology after in utero radiation and postnatal hyperthermia in rats.
AB  - In utero irradiation (IR) and postnatal hyperthermia (HT) exposure cause
      infertility by decreasing spermatogenic colony growth and the number of sperm in
      rats. Four groups were used: (i) Control group, (ii) HT group (rats exposed to
      hyperthermia on the 10th postnatal day), (iii) IR group (rats exposed to IR on
      the 17th gestational day) and (iv) IR + HT group. Three and six months after the
      procedures testes were examined by light and electron microscopy. Some
      degenerated tubules in the HT group, many vacuoles in spermatogenic cells and
      degenerated tight junctions in the IR group, atrophic tubules and severe
      degeneration of tight junctions in the IR + HT group were observed. ZO-1 and
      occludin immunoreactivity were decreased and disorganized in the HT and IR groups
      and absent in the IR + HT group. The increase in the number of apoptotic cells
      was accompanied by a time-dependent decrease in haploid, diploid and tetraploid
      cells in all groups. Degenerative findings were severe after 6 months in all
      groups. The double-hit model may represent a Sertoli cell only model of
      infertility due to a decrease in spermatogenic cell and alterated blood-testis
      barrier proteins in rat.

PMID- 23136997
TI  - Analysis of miR-376 RNA cluster members in the mouse inner ear.
AB  - Mutations in phosphoribosyl pyrophosphate synthetase 1 (PRPS1) are associated
      with a spectrum of non-syndromic to syndromic hearing loss. PRPS1 transcript
      levels have been shown to be regulated by the microRNA-376 genes. The long
      primary RNA transcript of the miR-376 RNA cluster members undergo extensive and
      simultaneous A -> I editing at one or both of two specific sites (+4 and +44) in
      particular human and mouse tissues. The PRPS1 gene, which contains target sites
      for the edited version of miR-376a-5p within its 3'UTR, has been shown to be
      repressed in a tissue-specific manner. To investigate whether the transcription
      of Prps1 is regulated by miR-376 cluster members in the mouse inner ear, we first
      quantified the expression of the mature miR-376 RNAs by quantitative real-time
      PCR. The spatio-temporal patterns of miR-376 expression were assessed by in situ
      hybridization. Finally, we examined whether A ->I editing of pri-miR-376 RNAs
      occurs in mouse inner ear by direct sequencing. Our data showed that the miR-376a
      3p, b-3p, c-3p are present in mouse embryonic inner ears and intensive expression
      of miR-376a-3p/b-3p was detected in the sensory epithelia and ganglia of both
      auditory and vestibular portions of the inner ear. In adult inner ear, the
      expression of miR-376a-3p/b-3p is restricted within ganglion neurons of auditory
      and vestibular systems as well as the cells in the stria vascularis. Only
      unedited pri-miR-376 RNAs were detected in the cochlea suggesting that the
      activity of PRPS1 in the inner ear may not be regulated through the editing of
      miR-376 cluster.

PMID- 23136998
TI  - Discriminative EPR detection of NO and HNO by encapsulated nitronyl nitroxides.
AB  - Nitric oxide, *NO, is one of the most important molecules in the biochemistry of
      living organisms. By contrast, nitroxyl, NO-, one-electron reduced analog of *NO
      which exists at physiological conditions in its protonated form, HNO, has been
      relatively overlooked. Recent data show that HNO might be produced endogenously
      and display unique biological effects. However, there is a lack of specific and
      quantitative methods of detection of endogenous HNO production. Here we present a
      new method for discriminative *NO and HNO detection by nitronyl nitroxides (NNs)
      using electron paramagnetic resonance (EPR). It was found that NNs react with *NO
      and HNO with similar rate constants of about 10(4) M(-1) s(-1) but yield
      different products: imino nitroxides and the hydroxylamine of imino nitroxides,
      correspondingly. An EPR approach for discriminative *NO and HNO detection using
      liposome-encapsulated NNs was developed. The membrane barrier of liposomes
      protects NNs against reduction in biological systems while is permeable to both
      analytes, *NO and HNO. The sensitivity of this approach for the detection of the
      rates of *NO/HNO generation is about 1 nM/s. The application of encapsulated NNs
      for real-time discriminative *NO/HNO detection might become a valuable tool in
      nitric oxide-related studies.

PMID- 23136999
TI  - Role of rs1533428 and rs12994401 in patients with Primary Open Angle Glaucoma in
      an European population.
AB  - PURPOSE: Genetic factors have been shown to play a remarkable role in the
      pathophysiology of glaucoma. Recently, two polymorphisms (rs1533428 and
      rs12994401) on chromosome 2p were found to be strongly associated with POAG in an
      Afro-Caribbean population in Barbados, West Indies. As data with regard to the
      role of these polymorphisms in a Caucasian population are lacking, the present
      study was set to investigate a hypothetical association between these
      polymorphisms and POAG in a Caucasian population. METHODS: In total 723
      participants were included in this study comprising 366 patients with POAG and
      357 control subjects from the southern part of Austria. Genotyping of rs1533428
      and rs12994401 was performed using polymerase chain reaction. RESULTS: Allelic
      frequencies and genotype distributions of rs1533428 and rs12994401 did not show
      statistical significance between patients with POAG and control subjects (p <
      0.05). Presence of the rs1533428 T-allele was associated with an odds ratio of
      0.95 (95% CI: 0.76-1.19; p = 0.69) for POAG, while the rs12994401 T-allele was
      associated with an odds ratio of 0.94 (95% CI: 0.73-1.21; p = 0.65) for POAG.
      CONCLUSION: Our data suggest that rs1533428 and rs12994401 themselves are
      unlikely major risk factors for POAG in a Central European population.

PMID- 23137000
TI  - Novel susceptibility genes associated with diabetic cataract in a Taiwanese
      population.
AB  - PURPOSE: To identify genetic variants that predispose to type 2 diabetes (T2D)
      with cataract. PATIENTS AND METHODS: Genome-wide association study (GWAS) of T2D
      patients with cataract, as graded by Lens Opacities Classification System (LOCS).
      A total of 109 T2D patients with cataract score equal to or above 10 designated
      as the study group, 649 T2D patients with cataract score equal to or below 3 as
      the control group. Single nucleotide polymorphisms (SNPs) with p-values < 10(-5)
      were considered to be putatively associated with the diabetic cataract. RESULTS:
      Fifteen SNPs were found to be putatively associated with diabetic cataract. These
      variants were located near the following genes: PPARD, CCDC102A, GBA3, NEDD9,
      GABRR1/2, RPS6KA2, tcag7.1163, TAC1, GALNTL1 and KIAA1671. We defined haplotype 1
      to haplotype 4 from the alternative alleles of related polymorphisms.
      Distribution of haplotype 2 on chromosome 4 and haplotype 4 on chromosome 7
      revealed significant differences (OR = 1.86 and 1.69, respectively; 95%
      confidence interval were 1.26-2.76 and 1.23-2.31, respectively). CONCLUSIONS: The
      15 loci coded on chromosomes 4, 6, 7, 14, 16 and 22 were associated with diabetic
      cataract. Gene functions are either with mechanisms of regulating blood sugar or
      formation of cataract. High linkage disequilibrium appeared on chromosome 4p15.31
      and chromosome 7q21.3.

PMID- 23137001
TI  - Aldol reactions with kinetic resolution: scope and limitations of ketal- and
      dithioketal-protected beta-ketoaldehydes.
AB  - The multiplicativity rule suggests that aldol coupling of chiral reactants will
      proceed with substantial mutual kinetic enantioselection (MKE) (racemic
      reactants) or via a highly enantioselective kinetic resolution (KR) (one
      enantiopure reactant) if the relative topicity is highly selective and the ketone
      enolate and aldehyde each have high diastereoface selectivity. The scope and
      limitations of that paradigm were explored by determining the stereoselectivities
      of aldol reactions of ketone 1a (known to give 3,5-trans aldol adducts with high
      selectivity) with a series of ketal- and dithioketal-protected beta-ketoaldehydes
      (+/-)-5 (predicted to have high Felkin diastereoface selectivity). Using racemic
      reactants, all reactions of the (c-Hex)(2)B enolates (highly anti-selective
      relative topicity) were remarkably selective and gave the 3,5-trans-3,1"-anti
      1",2"-syn adduct, one of eight possible diastereomers, via a diastereoselective
      (dr > 20) preferential reaction (MKE > 17) of like reactant enantiomers [i.e.,
      (3R)-1a + (R)-5 and (3S)-1a + (S)-5]. Reactions of the corresponding Ti(IV) "ate"
      enolates (anticipated syn-selective relative topicity) were much less selective,
      and only those of MOM-protected 1a with dithiolane-protected (+/-)-5 (i.e., X =
      S, n = 1) gave high selectivity in favor of the 3,5-trans-3,1"-syn-1",2"-syn
      adduct via a diastereoselective (dr > 20) preferential reaction (MKE >= 6) of
      unlike reactant enantiomers [i.e., (3R)-1a + (S)-5 and (3S)-1a + (R)-5].
      Analogous reactions of the (c-Hex)(2)B and Ti(IV) "ate" enolates of enantiopure
      (+)-1a (R = MOM) with (+/-)-5c (R(2) = Me, X = S, n = 1) occurred with KR to give
      the corresponding enantiopure adducts with the expected stereoselectivity. The
      adducts have applications in polyproionate synthesis.

PMID- 23137005
TI  - Predicting large CO2 adsorption in aluminosilicate zeolites for postcombustion
      carbon dioxide capture.
AB  - Large-scale simulations of aluminosilicate zeolites were conducted to identify
      structures that possess large CO(2) uptake for postcombustion carbon dioxide
      capture. In this study, we discovered that the aluminosilicate zeolite structures
      with the highest CO(2) uptake values have an idealized silica lattice with a
      large free volume and a framework topology that maximizes the regions with
      nearest-neighbor framework atom distances from 3 to 4.5 A. These predictors
      extend well to different Si:Al ratios and for both Na(+) and Ca(2+) cations,
      demonstrating their universal applicability in identifying the best-performing
      aluminosilicate zeolite structures.

PMID- 23137002
TI  - Candida colonisation and the efficacy of chlorhexidine gluconate on soft silicone
      lined dentures of diabetic and non-diabetic patients.
AB  - OBJECTIVES: The aim of this study was to evaluate Candida colonisation in the
      dentures with silicone soft liner in diabetic and non-diabetic patients and to
      assess the antifungal efficacy of chlorhexidine gluconate on Candida colonies.
      MATERIALS AND METHODS: Thirty patients with resorbed ridges, fifteen each in the
      diabetic and non-diabetic group, were selected. The mandibular denture of each
      patient was lined with heat-polymerised silicone resilient liner. Patients were
      instructed to clean the dentures with soap water and brush. Samples from the
      fitting surface of mandibular dentures were collected at 15, 21 and 30 days.
      Subsequently, samples were collected at 15, 21 and 30 days, after cleaning the
      dentures with a detergent solution of 4% chlorhexidine gluconate, and incubated
      for the evaluation of Candida growth. These data were subjected to statistical
      analysis by Mann-Whitney U-test. RESULTS: Normal oral flora in diabetics and non
      diabetics showed no difference (p > 0.05). The density of colonies increased
      after 21 and 30 days in diabetic patients (p < 0.05). Number of Candida colonies
      significantly reduced in both the groups after 21 and 30 days of cleaning the
      dentures with 4% chlorhexidine gluconate (p < 0.05). CONCLUSION: Dentures with
      silicone resilient liner exhibit increased Candida growth in diabetic patients.
      Four per cent chlorhexidine gluconate solution effectively disinfects these
      dentures.

PMID- 23137006
TI  - High genetic barrier nucleos(t)ide analogue(s) for prophylaxis from hepatitis B
      virus recurrence after liver transplantation: a systematic review.
AB  - The combination of hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogues
      [NA(s)] is considered as the standard of care for prophylaxis against HBV
      recurrence after liver transplantation (LT), but the optimal protocol is
      controversial. We evaluated the efficacy of the newer NAs with high genetic
      barrier (hgbNA) [i.e. entecavir (ETV) or tenofovir (TDF)] with or without HBIG as
      prophylaxis against HBV recurrence after LT. In total, 519 HBV liver transplant
      recipients from 17 studies met the inclusion criteria and they were compared to
      those under lamivudine (LAM) and HBIG who had been selected in our previous
      review. Patients under HBIG and LAM developed HBV recurrence (115/1889 or 6.1%):
      (a) significantly more frequently compared to patients under HBIG and a hgbNA
      [1.0% (3/303), p < 0.001], and (b) numerically but not significantly more
      frequently compared to the patients who received a newer NA after discontinuation
      of HBIG [3.9% (4/102), p = 0.52]. The use of a hgbNA without any HBIG offered
      similar antiviral prophylaxis compared to HBIG and LAM combination, if the
      definition of HBV recurrence was based on HBV DNA detectability [0.9% vs. 3.8%, p
      = 0.11]. Our findings favor the use of HBIG and a hgbNA instead of HBIG and LAM
      combined prophylaxis against HBV recurrence after LT.

PMID- 23137007
TI  - The effect of esthetic crown lengthening on perceptions of a patient's
      attractiveness, friendliness, trustworthiness, intelligence, and self-confidence.
AB  - BACKGROUND: Smile esthetics have been shown to play a major role in the
      perception of whether a person is attractive, and whether they are perceived as
      friendly, trustworthy, intelligent, and self-confident. A proposed major
      determinant of the esthetics of a smile is the amount of gingival display, which
      can be excessive in cases of altered passive eruption. The aim of this study is
      to see whether altering the amount of gingival display of patients would affect
      dental professionals' and laypersons' perceptions of the aforementioned social
      parameters. METHODS: Patients were identified as having altered passive eruption
      and excessive gingival display. Smiling "control" photographs were taken and then
      digitally altered so as to lengthen the teeth and thus reduce the amount of
      gingival display. These became the "test" photographs. The control and test
      photographs were shown in random order. The control group of evaluators consisted
      of senior dental students, and the test group of evaluators comprised students
      who had no formal dental training. Groups were asked to rate, on a visual analog
      scale, each picture's attractiveness, friendliness, trustworthiness,
      intelligence, and self-confidence. RESULTS: The test pictures with less gingival
      display were consistently and statistically significantly rated higher for all
      five social parameters than were their control counterparts (P <0.0001). When
      analyzed as an isolated effect, there were no statistically significant
      differences between the control group and the test group of evaluators when
      rating the pictures. Pictures depicting African Americans were judged to be more
      trustworthy (P = 0.0467) and self-confident (P = 0.0490) than pictures depicting
      white individuals. Pictures depicting women were judged to be more trustworthy (P
      = 0.0159) and intelligent (P = 0.0329) than pictures depicting men. All the
      social parameters were positively and statistically significantly correlated with
      each other (P <0.0001). CONCLUSIONS: Excessive gingival display did negatively
      affect how attractive a person's smile is judged to be. In addition, how
      friendly, trustworthy, intelligent, and self-confident a person was perceived to
      be was inversely related to the amount of gingival display. Untrained laypeople
      were just as sensitive to these differences as senior dental students.

PMID- 23137009
TI  - Pyrrole-based new diphosphines: Pd and Ni complexes bearing the PNP pincer
      ligand.
AB  - A new class of diphosphine PNP pincer ligand, 2,5
      bis(diphenylphosphinomethyl)pyrrole 2, was synthesized by the reaction between
      Ph2PH and 2,5-bis(dimethylaminomethyl)pyrrole in 90% yield. The analogous
      reaction of Ph2PH with 1,9-bis(dimethylaminomethyl)diphenyldipyrrolylmethane
      readily afforded a PNNP type diphosphine ligand, 1,9
      bis(diphenylphosphinomethyl)diphenyldipyrrolylmethane 5 in 92% yield. These
      phosphine compounds were oxidized with H2O2 and S8 to give the corresponding
      phosphoryl and thiophosphoryl compounds 6-9 in very good yields. The reaction of
      the PNP pincer ligand 2 with [PdCl2(PhCN)2] in the presence of Et3N afforded the
      mononuclear Pd(II) complex, [PdCl{C4H2N-2,5-(CH2PPh2)2-kappa(3)PNP}] 10 in 87%
      yield. Conversely, treatment of 2 with [PdCl2(PhCN)2] in the absence of Et3N gave
      the dinuclear Pd(II) complex [Pd2Cl4{MU-C4H3N-2,5-(CH2PPh2)2-kappa(2)PP}2], the
      structure which is proposed based on the spectroscopic data. When 2 was treated
      with Pd(0) precursor [Pd2(dba)3].CHCl3 the dinuclear Pd(I) complex [Pd2{MU-C4H2N
      2,5-(CH2PPh2)2-kappa(2)PN,kappa(1)P}2], 12, was obtained in 23% yield. The
      formation of complex 12 is solvent dependent, which transforms into complex 10 in
      CDCl3 as studied by variable temperature (1)H and (31)P NMR methods. Treatment of
      2 with [Ni(OAc)2].4H2O gave the mononuclear Ni(II) pincer complex [Ni(OAc){C4H2N
      2,5-(CH2PPh2)2-kappa(3)PNP}], 13, which upon treatment with an excess of LiCl or
      LiBr or KI afforded the respective halide ion substituted Ni(II) complexes,
      [NiX{C4H2N-2,5-(CH2PPh2)2-kappa(3)PNP}] (X = Cl, Br, and I), 14-16, in very good
      yields. The structures of 5, 2,5-bis(diphenylphosphorylmethyl)pyrrole 6, 10, 12,
      and 14-16 were determined by the single crystal X-ray diffraction method. In the
      structure of 12, two short contacts between the diagonally positioned Pd and P
      atoms are observed. To understand these weak interactions, density functional
      theory (DFT) calculations were done and an interaction MO diagram is presented. 

PMID- 23137008
TI  - Dietary intake of specific fatty acids and breast cancer risk among
      postmenopausal women in the VITAL cohort.
AB  - Studies of dietary fat intake and breast cancer have been inconsistent and few
      have examined specific fatty acids. We examined the association between specific
      monounsaturated (MUFA), polyunsaturated (PUFA), saturated (SFA), and trans-fatty
      acids (TFA) and breast cancer risk. Participants, 50-76 yr, were female members
      of the VITamins And Lifestyle (VITAL) Cohort, who were postmenopausal at
      baseline. In 2000-2002, participants completed a food frequency questionnaire.
      Seven hundred seventy-two incident, primary breast cancer cases were identified
      using a population-based cancer registry. Cox proportional hazard models
      estimated hazard ratios (HR) and 95% confidence intervals (95% CI) for the
      association between fatty acid intake and breast cancer risk. Intake of total
      MUFAs (highest vs. lowest quintile: HR = 1.61, 95% CI: 1.08-2.38, P trend =
      0.02), particularly myristoleic and erucic acids, was associated with increased
      breast cancer risk. Whereas total SFA was suggestive of an increased risk (HR =
      1.47, 95% CI: 1.00-2.15, P trend = 0.09), strong associations were observed for
      palmitic, margaric, and stearic acids. Total TFA and PUFA intake were not
      associated with breast cancer. However, among TFAs, linolelaidic acid was
      positively associated with risk; among PUFAs, intake of eicosapentaenoic and
      docosahexaenoic acids were inversely associated with risk. Our findings show that
      fatty acids are heterogeneous in their association with postmenopausal breast
      cancer risk.

PMID- 23137010
TI  - The genetic match between vaccine strains and circulating seasonal influenza A
      viruses in Vietnam, 2001-2009.
AB  - BACKGROUND: Vietnam is currently developing domestic capability to manufacture
      influenza vaccines but information on the genetic and antigenic characteristics
      of locally circulating seasonal influenza viruses is limited. To assess the
      relevance of WHO recommended vaccine strains to the situation in Vietnam, we
      analyzed the genetic relatedness of the hemagglutinin (HA) gene of seasonal
      influenza A viruses circulating in Vietnam from 2001 to 2009 to WHO recommended
      vaccine strains over the same period. METHODS AND PRINCIPAL FINDINGS: We
      sequenced the HA gene of 32 H1N1 and 44 H3N2 seasonal influenza A isolates from
      laboratory-based sentinel surveillance sites in Hanoi from 2001 to 2005 and from
      a national influenza surveillance system from 2005 to 2009. H1 and H3 HA
      phylogenetic trees rooted to vaccine strains A/Beijing/295/1995 (H1N1) and
      A/Moscow/10/1999 (H3N2), respectively, were constructed with contemporary HA
      sequences of isolates from neighboring countries. We found some genetic
      differences between seasonal influenza H3N2 viruses and three WHO influenza
      vaccine strains recommended for use in the Northern and Southern Hemispheres for
      the 2001-2004 and 2007-2008 seasons and close genetic identity of circulating
      H3N2 strains with the recommended WHO Southern Hemisphere vaccine strains for
      2004 and 2009 seasons. The genetic similarity of circulating H1N1 strains with
      the WHO recommended vaccine strains are described for the study period 2001-2009.
      CONCLUSIONS: The HA gene of seasonal influenza virus strains in Vietnam
      (especially influenza A/H3N2) showed varying degrees of genetic identity compared
      with those of the Northern or Southern Hemisphere vaccine strains recommended by
      WHO. The close relatedness of the HA of Vietnamese strains and contemporary
      strains from nearby countries indicate a good genetic match of circulating
      strains during study period. Greater representation of virus isolates from South
      East Asia in the vaccine strain selection process is desirable of influenza
      vaccine development in Vietnam.

PMID- 23137011
TI  - Identification of differentially expressed genes in the oviduct of two rabbit
      lines divergently selected for uterine capacity using suppression subtractive
      hybridization.
AB  - Suppressive subtractive hybridization libraries from oviduct at 62 h post-mating
      of two lines of rabbits divergently selected for uterine capacity were generated
      to identify differentially expressed genes. A total of 438 singletons and 126
      contigs were obtained by cluster assembly and sequence alignment of 704 expressed
      sequence tags (ESTs), of which 54% showed homology to known proteins of the non
      redundant NCBI databases. Differential screening by dot blot validated 71 ESTs,
      of which 47 showed similarity to known genes. Transcripts of genes were
      functionally annotated in the molecular function and the biological process gene
      ontology categories using the BLAST2GO software and were assigned to reproductive
      developmental process, immune response, amino acid metabolism and degradation,
      response to stress and apoptosis terms. Finally, three interesting genes, PGR,
      HSD17B4 and ERO1L, were identified as overexpressed in the low line using RT
      qPCR. Our study provides a list of candidate genes that can be useful to
      understanding the molecular mechanisms underlying the phenotypic differences
      observed in early embryo survival and development traits.

PMID- 23137012
TI  - Lipids are required for the development of Brazil nut allergy: the role of mouse
      and human iNKT cells.
AB  - BACKGROUND: Lipids are required for mice sensitization to Ber e 1, Brazil nut
      major allergen. Here, we characterized different lipid fractions extracted from
      Brazil nuts and the lipid-binding ability of Ber e 1. Further, we determined
      their in vivo ability to induce Ber-specific anaphylactic antibodies and the role
      of invariant natural killer T (iNKT) cells in this process. METHODS: Wild-type
      (WT) and iNKT cell-deficient mice were sensitized with Ber e 1 and specific lipid
      fractions, and anaphylactic antibodies were measured by enzyme-linked
      immunosorbent assay (ELISA) and passive cutaneous anaphylaxis (PCA). The lipid
      binding characteristic of Ber e 1 (Ber) was established by using fluorescent
      probes and (15) N-labeled NMR. In vitro production of IL-4 was determined in
      Ber/lipid C-stimulated mouse iNKT cells and human T-cell lines containing NKTs
      primed with CD1d+C1R transfectants by flow cytometry and ELISA, respectively.
      RESULTS: Only one specific lipid fraction (lipid C), containing neutral and
      common phospholipids, induced Ber anaphylactic antibodies in mice. Ber e 1 has a
      lipid-binding site, and our results indicated an interaction between Ber e 1 and
      lipid C. iNKT-deficient mice produced lower levels of anaphylactic antibodies
      than WT mice. In vitro, Ber/lipid C-stimulated murine iNKT cells produced IL-4
      but not IFN-gamma. Human T-cell lines derived from nut-allergic patients produced
      IL-4 to Ber/lipid C in a CD1d- and dose-dependent manner. CONCLUSION: Lipid
      fraction C from Brazil nut presents an essential adjuvant activity to Ber e 1
      sensitization, and iNKT cells play a critical role in the development of Brazil
      nut-allergic response.

PMID- 23137014
TI  - Carrier cooling in colloidal quantum wells.
AB  - It has recently become possible to chemically synthesize atomically flat
      semiconductor nanoplatelets with monolayer-precision control over the platelet
      thickness. It has been suggested that these platelets are quantum wells; that is,
      carriers in these platelets are confined in one dimension but are free to move in
      the other two dimensions. Here, we report time-resolved photoluminescence and
      transient-absorption measurements of carrier relaxation that confirm the quantum
      well nature of these nanomaterials. Excitation of the nanoplatelets by an intense
      laser pulse results in the formation of a high-temperature carrier population
      that cools back down to ambient temperature on the time scale of several
      picoseconds. The rapid carrier cooling indicates that the platelets are well
      suited for optoelectronic applications such as lasers and modulators.

PMID- 23137013
TI  - Cost-effectiveness analysis of different rescue therapies in patients with
      lamivudine-resistant chronic hepatitis B in China.
AB  - BACKGROUND: Several rescue therapies have been used in patients with lamivudine
      (LAM)-resistant chronic hepatitis B (CHB); however, the economic outcome of these
      therapies is unclear. The object of the current analysis was to evaluate the
      lifetime cost-effectiveness of rescue therapies among patients with LAM-resistant
      CHB. METHODS: A Markov model was developed to simulate the clinical course of
      patients with LAM-resistant CHB. From the perspective of Chinese health care, a
      lifetime cost-utility analysis was performedfor 4 rescue strategies: adefovir
      (ADV), entecavir (ETV) or tenofovir (TDF) monotherapy and combination therapy
      using LAM and ADV. A hypothetical cohort of 45-year-old patients with genotypic
      or clinical LAM-resistant CHB entered the model, and the beginning health state
      was LAM-resistant CHB without other complications. The transition probabilities,
      efficacy and resistance data for each rescue therapy as well as the costs and
      utility data were estimated from the literature. The discount rate (3%) utilized
      for costs and benefits. Sensitivity analyses were used to explore the impact of
      uncertainty on the results. RESULTS: In LAM-resistant HBeAg-positive and HBeAg
      negative CHB cohorts, TDF monotherapy and combination therapy were on the
      efficiency frontier for both positive and negative populations. Compared with no
      treatment, the use of combination therapy cost an additional $6,531.7 to gain 1
      additional quality-adjusted life year (QALY) for HBeAg-positive patients and
      $4,571.7 to gain 1 additional QALY for HBeAg-negative patients. TDF monotherapy
      for HBeAg-positive patients, shows greater increase in QALYs but higher
      incremental cost-effectiveness ratio (ICER) in comparison with combination
      therapy. In probabilistic sensitivity analyses, combination therapy was the
      preferred option for health care systems with limited health resources, such as
      Chinese health care system. CONCLUSION: In Chinese patients with LAM-resistant
      CHB, combination therapy is a more cost-effective option than the competing
      rescue therapies.

PMID- 23137016
TI  - Serum IgA reactivity against GroEL of Streptococcus sanguinis and human
      heterogeneous nuclear ribonucleoprotein A2/B1 in patients with Behcet disease.
AB  - BACKGROUND: Infectious agents, especially Streptococcus sanguinis and herpes
      simplex virus, have long been postulated as major triggering factors for Behcet
      disease (BD). OBJECTIVES: To identify an anti-S. sanguinis antigen reacting with
      serum IgA antibody in patients with BD. METHODS: We detected a target protein by
      proteomics analysis and evaluated serum IgA reactivity of 100 patients with BD
      against the identified streptococcal target protein and human heterogeneous
      nuclear ribonucleoprotein (hnRNP) A2/B1. Homologous epitope sequences between the
      streptococcal target protein and human hnRNP A2/B1 were also evaluated. RESULTS:
      Four protein bands were detected by immunoprecipitation, and chaperonin GroEL was
      identified by a proteomics analysis. Reactivity of serum IgA against recombinant
      S. sanguinis GroEL was detected in 77 of 100 patients with BD (77%) and in 21 of
      70 healthy controls (30%). In addition, reactivity of serum IgA against human
      recombinant hnRNP A2/B1 was seen in 79 of 100 patients with BD (79%) and in eight
      of 70 healthy controls (11%). Among the eight distinctive epitopes with
      significant homology between S. sanguinis GroEL and human hnRNP A2/B1, the serum
      IgA reactivity of patients with BD was markedly higher with epitope 3 (hnRNP
      A2/B1 peptide 33-46 and GroEL peptide 57-70) and epitope 6 (hnRNP A2/B1 peptide
      177-188 and GroEL peptide 347-358). CONCLUSION: We identified an S. sanguinis
      GroEL protein as a target of serum anti-S. sanguinis IgA antibody reactivity in
      patients with BD. In addition, patients with BD exhibited serum IgA reactivity
      against homologous epitope regions between S. sanguinis GroEL and human hnRNP
      A2/B1.

PMID- 23137017
TI  - An ovine in vitro model for chondrocyte-based scaffold-assisted cartilage grafts.
AB  - BACKGROUND: Scaffold-assisted autologous chondrocyte implantation is an effective
      clinical procedure for cartilage repair. From the regulatory point of view, the
      ovine model is one of the suggested large animal models for pre-clinical studies.
      The aim of our study was to evaluate the in vitro re-differentiation capacity of
      expanded ovine chondrocytes in biomechanically characterized polyglycolic acid
      (PGA)/fibrin biomaterials for scaffold-assisted cartilage repair. METHODS: Ovine
      chondrocytes harvested from adult articular cartilage were expanded in monolayer
      and re-assembled three-dimensionally in PGA-fibrin scaffolds. De- and re
      differentiation of ovine chondrocytes in PGA-fibrin scaffolds was assessed by
      histological and immuno-histochemical staining as well as by real-time gene
      expression analysis of typical cartilage marker molecules and the matrix
      remodelling enzymes matrix metalloproteinases (MMP) -1, -2 and -13 as well as
      their inhibitors. PGA scaffolds characteristics including degradation and
      stiffness were analysed by electron microscopy and biomechanical testing.
      RESULTS: Histological, immuno-histochemical and gene expression analysis showed
      that dedifferentiated chondrocytes re-differentiate in PGA-fibrin scaffolds and
      form a cartilaginous matrix. Re-differentiation was accompanied by the induction
      of type II collagen and aggrecan, while MMP expression decreased in prolonged
      tissue culture. Electron microscopy and biomechanical tests revealed that the non
      woven PGA scaffold shows a textile structure with high tensile strength of 3.6
      N/mm2 and a stiffness of up to 0.44 N/mm2, when combined with gel-like fibrin.
      CONCLUSION: These data suggest that PGA-fibrin is suited as a mechanically stable
      support structure for scaffold-assisted chondrocyte grafts, initiating
      chondrogenic re-differentiation of expanded chondrocytes.

PMID- 23137018
TI  - Diagnostic correlation between the expression of the DNA repair enzyme N
      methylpurine DNA glycosylase and esophageal adenocarcinoma onset: a retrospective
      pilot study.
AB  - EAC in its early stages, when it can potentially be cured, is rarely symptomatic
      and is associated with high mortality rates because in part of late-stage
      diagnosis. Given that DNA repair is an important contributory factor of early
      stage malignancy, our study focused on the expression of the base excision repair
      enzyme N-methylpurine DNA glycosylase (MPG) in EAC disease onset. MPG messenger
      RNA (mRNA) expression levels were determined using quantitative reverse
      transcriptase polymerase chain reaction from a maximum of 72 patient samples.
      Immunohistochemistry was further utilized for the detection of MPG protein, and
      semiquantitative analysis performed using an H-score approach was carried out on
      a total of 130 archival tissue samples of different esophageal pathologies.
      Nuclear localized MPG protein was detected in all nonmalignant tissues derived
      from the enterohepatic system, with H-score values of 3.9-5.5 +/- 0.4-1.0. In
      cancerous tissues derived from the enterohepatic system, a 9.5-fold increase in
      the level of MPG mRNA expression was specifically observed in the malignant
      regions located within the esophagus region. Further analysis revealed a 9- and
      14-fold increase in MPG mRNA expression in EAC tumor, node, metastasis stages II
      and III, respectively, suggesting MPG expression to correlate with EAC disease
      progression. Immunohistochemistry analysis further showed a sevenfold significant
      increase in MPG protein expression in EAC tissues. Intriguingly, there was a
      fivefold significant decrease in nuclear localized MPG protein expression in
      tissues derived from Barrett's esophagus and low-grade dysplasia. Such findings
      highlight a complex regulatory pattern governing DNA glycosylase base excision
      repair initiation, as normal tissue undergoes Barrett's metaplasia and later
      dedifferentiates to EAC. Indeed, disease-stage-specific alterations in the
      expression of MPG may highlight a potential role for MPG in determining EAC onset
      and thus potentially be of clinical relevance for early disease detection and
      increased patient survival.

PMID- 23137019
TI  - Current perspectives in bladder cancer management.
AB  - More than 350,000 new cases of bladder cancer are diagnosed worldwide each year;
      the vast majority (> 90%) of these are transitional cell carcinomas (TCC). The
      most important risk factors for the development of bladder cancer are smoking and
      occupational exposure to toxic chemicals. Painless visible haematuria is the most
      common presenting symptom of bladder cancer; significant haematuria requires
      referral to a specialist urology service. Cystoscopy and urine cytology are
      currently the recommended tools for diagnosis of bladder cancer. Excluding muscle
      invasion is an important diagnostic step, as outcomes for patients with muscle
      invasive TCC are less favourable. For non-muscle invasive bladder cancer,
      transurethral resection followed by intravesical chemotherapy (typically
      Mitomycin C or epirubicin) or immunotherapy [bacillus Calmette-Guerin (BCG)] is
      the current standard of care. For patients failing BCG therapy, cystectomy is
      recommended; for patients unsuitable for surgery, the choice of treatment options
      is currently limited. However, novel interventions, such as chemohyperthermia and
      electromotive drug administration, enhance the effects of conventional
      chemotherapeutic agents and are being evaluated in Phase III trials. Radical
      cystectomy (with pelvic lymphadenectomy and urinary diversion) or radical
      radiotherapy are the current established treatments for muscle invasive TCC.
      Neoadjuvant chemotherapy is recommended before definitive treatment of muscle
      invasive TCC; cisplatin-containing combination chemotherapy is the recommended
      regimen. Palliative chemotherapy is the first-choice treatment in metastatic TCC.

PMID- 23137020
TI  - Safety and hemostatic efficacy of fibrin pad in partial nephrectomy: results of
      an open-label phase I and a randomized, standard-of-care-controlled phase I/II
      study.
AB  - BACKGROUND: Bleeding severity, anatomic location, tissue characteristics, and
      visibility are common challenges encountered while managing intraoperative
      bleeding, and conventional hemostatic measures (suture, ligature, and cautery)
      may sometimes be ineffective or impractical. While topical absorbable hemostats
      (TAH) are useful hemostatic adjuvants, each TAH has associated disadvantages.
      METHODS: We evaluated the safety and hemostatic efficacy of a new advanced
      biologic combination product-fibrin pad-to potentially address some gaps
      associated with TAHs. Fibrin pad was assessed as adjunctive hemostat in open
      partial nephrectomy in single-center, open-label, Phase I study (N = 10), and as
      primary hemostat in multicenter, single-blind, randomized, standard-of-care (SOC)
      controlled Phase I/II study (N = 7) in Israel. It was used to control mild-to
      moderate bleeding in Phase I and also spurting arterial bleeding in Phase I/II
      study. Phase I study assessed safety and Phase I/II study, proportion of
      successes at 10 min following randomization, analyzed by Fisher exact tests at 5%
      significance level. RESULTS: Phase I (N = 10): All patients completed the study.
      Hemostasis was achieved within 3-4 min (average = 3.1 min) of a single
      application in all patients. Fibrin pad was found to be safe for human use, with
      no product-related adverse events reported. Phase I/II (N = 7): Hemostatic
      success at 10 min (primary endpoint) was achieved in 3/4 patients treated with
      fibrin pad versus 0/3 patients treated with SOC. No clinically significant change
      in laboratory or coagulation parameters was recorded, except a case of post
      procedural hemorrhage with fibrin pad, which was considered serious and related
      to the fibrin pad treatment, and required re-operation. Although Data Safety
      Monitoring Board authorized trial continuation, the sponsor decided against
      proceeding toward an indication for primary treatment of severe arterial
      hemorrhage as a replacement for sutures. The study was suspended after 7/30
      planned subjects were enrolled. CONCLUSIONS: The first-in-man trial of fibrin pad
      demonstrated its safety and efficacy as an adjunctive hemostatic technique for
      mild-to-moderate bleeding in partial nephrectomy. The study also suggested that
      the product should not replace sutures or meticulous surgical techniques for the
      treatment of severe arterial hemorrhage. TRIAL REGISTRATION: Phase I/II trial,
      NCT00598130.

PMID- 23137021
TI  - Evaluation of a continuous blood glucose monitoring system using a central venous
      catheter with an integrated microdialysis function.
AB  - INTRODUCTION: Glycemic control in critically ill patients has been the topic of
      an interesting debate during the last decade. An accurate continuous glucose
      monitoring system is essential to better understand this field. This prospective
      study thus evaluates the accuracy and technical feasibility of a continuous
      glucose monitoring system using intravascular microdialysis. PATIENTS AND
      METHODS: Thirty patients undergoing cardiac surgery were monitored using a triple
      lumen central venous catheter (Eirus TLC; Eirus Medical AB, Solna, Sweden) with
      an integrated microdialysis function. The catheter functions as a central venous
      catheter, enabling blood sampling and administration of infusions and medication
      while simultaneously providing continuous glucose monitoring. The patients were
      monitored for up to 48 h postoperatively. As reference, arterial blood gas
      samples were taken every hour and analyzed in a blood gas analyzer. RESULTS: Six
      hundred seven paired samples were obtained for analysis. Using Clarke Error Grid
      analysis, 100% of the paired samples were in Zones A+B, and 97% were in Zone A.
      Mean difference (bias) was -0.12 mmol/L, and mean absolute relative difference
      was 5.6%. Of the paired samples, 97.5% were correct according to International
      Organization for Standardization criteria. Bland-Altman analysis showed bias +/-
      limits of agreement were -0.12 +/- 0.7 mmol/L. No hypoglycemic episodes were
      observed. CONCLUSIONS: Central venous microdialysis is an accurate and reliable
      method for continuous blood glucose monitoring up to 48 h in patients undergoing
      cardiac surgery. With the microdialysis function integrated in a central venous
      catheter, no extra device for the continuous glucose monitoring is required. The
      system may be useful in critically ill patients.

PMID- 23137022
TI  - Hepatic expression and serum levels of syndecan 1 (CD138) in patients with
      nonalcoholic fatty liver disease.
AB  - BACKGROUND AND AIMS: Syndecan-1 (CD138) is a transmembrane heparan sulfate
      proteoglycan expressed in the liver which may exert metabolic effects by
      mediating the hepatic clearance of triglyceride-rich lipoproteins. In the present
      study, we assayed serum levels and the hepatic expression of syndecan-1 and
      examined their association with clinical, biochemical, and histologic phenotypes
      in patients with histology-proven nonalcoholic fatty liver disease (NAFLD).
      METHODS: A total of 59 patients with biopsy-proven NAFLD and 54 matched controls
      were enrolled. The analysis of syndecan-1 expression in liver biopsies was
      performed by immunohistochemistry on formalin-fixed, paraffin-embedded samples.
      Serum syndecan-1 levels were measured by ELISA. RESULTS: NAFLD patients had
      significantly higher serum syndecan-1 levels [median: 61 ng/mL (interquartile
      range: 36-97 ng/mL)] than controls [median: 37 ng/mL (interquartile range: 25-59
      ng/mL, Mann-Whitney U test, p < 0.001]. However, we did not find any significant
      association between serum syndecan-1 and the mean syndecan-1 immunohistochemical
      score (n = 59, r = 0.064, p = 0.63). Interestingly, the syndecan-1
      immunohistochemical score was an independent predictor of HDL cholesterol in
      NAFLD patients (beta = 0.27; t = 1.99, p < 0.05). CONCLUSIONS: Our data suggest
      that serum syndecan-1 levels are raised in patients with NAFLD. Moreover, the
      syndecan-1 immunohistochemical score in the liver is independently associated
      with HDL cholesterol in this group of patients. These pilot results support
      further investigation of this molecule in metabolic liver diseases.

PMID- 23137023
TI  - Structural and Sensory Characterization of Bitter Tasting Steroidal Saponins from
      Asparagus Spears (Asparagus officinalis L.).
AB  - Application of sequential solvent extraction and iterative chromatographic
      separation in combination with taste dilution analysis recently revealed a series
      of steroidal saponins as the key contributors to the typical bitter taste of
      white asparagus spears (Asparagus officinalis L.). Besides six previously
      reported saponins, (25R)-furost-5-en-3beta,22,26-triol-3-O-[alpha-L
      rhamnopyranosyl-(1->4)-beta-D-glucopyranoside]-26-O-beta-D-glucopyranoside, (25R)
      furostane-3beta,22,26-triol-3-O-[alpha-L-rhamnopyranosyl-(1->4)-beta-D
      glucopyranoside]-26-O-beta-D-glucopyranoside, and (25S)-furostane-3beta,22,26
      triol-3-O-[alpha-L-rhamnopyranosyl-(1->4)-beta-D-glucopyranoside]-26-O-beta-D
      glucopyranoside, and 3-O-[{alpha-L-rhamnopyranosyl-(1->2)}{alpha-L
      rhamnopyranosyl-(1->4)}-beta-D-glucopyranosyl]-(25S)-spirost-5-ene-3beta-ol were
      identified for the first time as key bitter compounds in the edible spears of
      white asparagus by means of LC-MS/MS, LC-TOF-MS, 1D/2D-NMR spectroscopy, and
      hydrolysis experiments. This paper presents the isolation, structure
      determination, and sensory activity of these saponins. Depending on their
      chemical structure, the saponins identified showed human bitter recognition
      thresholds between 10.9 and 199.7 MUmol/L (water).

PMID- 23137024
TI  - Genetic and protein markers related to laryngeal epithelial precursor lesions and
      their neoplastic progression.
AB  - CONCLUSION: Various biomarkers might ultimately prove to have prognostic value
      and could be clinically relevant. It is mandatory confirm the prognostic power of
      these markers in large, well-designed, and prospective studies. OBJECTIVE: The
      aim of this study was to investigate the possible role of specific genes and
      proteins in laryngeal tumorigenesis. METHODS: Genetic analysis by multiple
      ligation-dependent probe amplification and analysis of protein expression by
      immunohistochemistry were carried out in a series of 50 tissue samples. RESULTS:
      In the smoker normal mucosa group TP53 loss was predominant, whereas in the
      epithelial precursor lesions (EPLs) CDKN2A loss and BCL2L1 gain were most
      frequent. EPL with progression presented CTNNB1 loss. Positivity at cytoplasm for
      beta-catenin, cyclin D1 and p53 was detected in all EPL cases with progression to
      invasive carcinoma. Multivariate analysis showed that expression of beta-catenin
      and loss of CTTNB1 were associated with laryngeal cancer risk.

PMID- 23137025
TI  - Serum melatonin levels and antioxidant capacities after consumption of pineapple,
      orange, or banana by healthy male volunteers.
AB  - Melatonin is a naturally occurring molecule biosynthesized by the pineal gland of
      vertebrates; it also has been identified in many plants. It is considered an
      important antioxidant and may retard the development of some neurodegenerative
      diseases and cancer. Previous studies in humans have measured melatonin
      metabolites in urine and have indicated that melatonin-containing foods may
      provide dietary melatonin. This study tested whether the consumption of fruits or
      fruit juice containing melatonin would influence the serum melatonin
      concentration and antioxidant status. In this crossover study, 12 healthy male
      volunteers took either juice extracted from one kilogram of orange or pineapple
      or two whole bananas, with a 1-wk washout period between the fruit or fruit
      juices. An enzyme-linked immunosorbent (ELISA) assay was used to determine the
      serum melatonin concentration. Serum antioxidant capacity was determined by
      ferric reducing antioxidant power (FRAP) assay and oxygen radical antioxidant
      capacity (ORAC) assay. The highest serum melatonin concentration was observed at
      120 min after fruit consumption, and compared with before consumption levels,
      their values were significantly increased for pineapple (146 versus 48 pg/mL P =
      0.002), orange (151 versus 40 pg/mL, P = 0.005), and banana (140 versus 32 pg/mL,
      P = 0.008), respectively. Serum antioxidant capacity following fruit consumption
      also significantly increased in both the FRAP (7-14% increase, P <= 0.004) and
      ORAC (6-9% increase, P = 0.002) assays. Both the serum FRAP and ORAC values
      strongly correlated with serum melatonin concentration for all three fruits.
      These findings suggest that tropical fruit consumption increases the serum
      melatonin concentrations and also raises the antioxidant capacity in the serum of
      healthy volunteers in proportion to serum melatonin levels. 

PMID- 23137026
TI  - O2-functionalized methylamine diazeniumdiolates: evidence for E ? Z equilibration
      in an acyclic system.
AB  - Diazeniumdiolates that have the structure RHN-N(O)?NOR' are of interest as
      prodrug (caged) forms of the bioeffectors nitric oxide (NO) and nitroxyl (HNO).
      Previous work has focused on examples possessing alpha-branched R groups, with
      isopropylamine (IPA)/NO (R = isopropyl) being the smallest examined to date. To
      probe the effect of minimizing the alkyl-group size on the chemistry of IPA/NO,
      we prepared the corresponding methylamine derivative as a sodium salt that was
      highly unstable but could be trapped in very low overall yield as the stable O(2)
      benzyl derivative. To prepare enough for efficient characterization, we devised
      an alternate synthesis involving a novel N-dealkylation route. CH(3)HN-N(O)?NOBn,
      synthesized in high yield and crystallized as the Z isomer as determined by X-ray
      crystallography, was observed to exist as a 11:1 mixture of two isomeric forms in
      dynamic equilibrium in solution. Similar results were seen for the O(2)-ethyl
      derivative, whose two equilibrium constituents were partially separated by HPLC
      to reveal essentially identical UV and mass spectra, indicating them to be Z and
      E isomers of CH(3)HN-N(O)?NOEt. The results could lead the way to a fuller
      understanding of the chemistry of the acyclic (E)-diazeniumdiolates.

PMID- 23137027
TI  - Intrathecal "microdosing": reality or artifact?

PMID- 23137028
TI  - Dietary folate suppresses DMH-induced colon carcinogenesis in a rat model and
      affects DMH-induced expression of four DNA repair enzymes.
AB  - This study investigated the potential role of folate in the dimethylhydrazine
      (DMH) colon cancer model in male Wistar rats. For induction of colon cancer,
      group 1 rats were injected subcutaneously with 30 mg DMH/kg body weight weekly
      for 30 wk. Group 2 received DMH vehicle. Group 3 rats received DMH as in Group 1
      but their diet was supplemented with 8 mg folate/kg diet. Group 4 was fed diet
      supplemented with 8 mg folate/kg diet. Upregulation of DNA damage repair genes
      Apurinic/apyrimidinic endonuclease 1, X-ray repair complementing defective repair
      in Chinese hamster cells 5, 8-oxoguanine-DNA glycosylase, and proliferating cell
      nuclear antigen, associated with a reduction of folic acid level was observed in
      colons of DMH group. Reductions of these gene upregulations and a significant
      increase of colonic folic acid level occurred in the DMH group supplemented with
      folic acid and this group also had significant inhibition of tumor incidence,
      normal survival rate and histologically nearly normal colonic architecture. It
      can be concluded that folate supplementation exerts a potent protective effect on
      rat colon carcinogenesis via significant modulation of DNA repair, providing a
      mechanism by which it plays a role in the etiology of human cancer.

PMID- 23137029
TI  - Two-dimensional tetragonal TiC monolayer sheet and nanoribbons.
AB  - We report a two-dimensional tetragonal Titanium Carbide (TiC) monolayer sheet
      with distinguished structure and properties based on comprehensive first
      principles calculations. The TiC sheet exhibits a novel zigzag-shaped buckling
      structure with all atoms being quasiplanar tetracoordinate, as favored by strong
      in-plane C2p-Ti3d bonding and synergetic out-of-plane electronic delocalization.
      This unique structure endows the sheet with high kinetic stability and
      anisotropic mechanical properties. Moreover, the TiC sheet displays orientation
      dependent electronic properties derived from its special rectangular symmetry,
      with indirect band gap of ~0.2 eV and substantial ferromagnetism along its edges,
      thus promising for wide applications in nanoelectronics.

PMID- 23137032
TI  - Environmental speciation of actinides.
AB  - Although minor in abundance in Earth's crust (U, 2-4 ppm; Th, 10-15 ppm) and in
      seawater (U, 0.003 ppm; Th, 0.0007 ppm), light actinides (Th, Pa, U, Np, Pu, Am,
      and Cm) are important environmental contaminants associated with anthropogenic
      activities such as the mining and milling of uranium ores, generation of nuclear
      energy, and storage of legacy waste resulting from the manufacturing and testing
      of nuclear weapons. In this review, we discuss the abundance, production, and
      environmental sources of naturally occurring and some man-made light actinides.
      As is the case with other environmental contaminants, the solubility, transport
      properties, bioavailability, and toxicity of actinides are dependent on their
      speciation (composition, oxidation state, molecular-level structure, and nature
      of the phase in which the contaminant element or molecule occurs). We review the
      aqueous speciation of U, Np, and Pu as a function of pH and Eh, their interaction
      with common inorganic and organic ligands in natural waters, and some of the
      common U-containing minerals. We also discuss the interaction of U, Np, Pu, and
      Am solution complexes with common Earth materials, including minerals, colloids,
      gels, natural organic matter (NOM), and microbial organisms, based on simplified
      model system studies. These surface interactions can inhibit (e.g., sorption to
      mineral surfaces, formation of insoluble biominerals) or enhance (e.g., colloid
      facilitated transport) the dispersal of light actinides in the biosphere and in
      some cases (e.g., interaction with dissimilatory metal-reducing bacteria, NOM, or
      Mn- and Fe-containing minerals) can modify the oxidation states and,
      consequently, the behavior of redox-sensitive light actinides (U, Np, and Pu).
      Finally, we review the speciation of U and Pu, their chemical transformations,
      and cleanup histories at several U.S. Department of Energy field sites that have
      been used to mill U ores, produce fissile materials for reactors and weapons, and
      store high-level nuclear waste from both civilian and defense operations,
      including Hanford, WA; Rifle, CO; Oak Ridge, TN; Fernald, OH; Fry Canyon, UT; and
      Rocky Flats, CO.

PMID- 23137031
TI  - Fluoxetine induces hepatic lipid accumulation via both promotion of the SREBP1c
      related lipogenesis and reduction of lipolysis in primary mouse hepatocytes.
AB  - AIMS: In this study, we investigated the peripheral mechanisms underlying the
      metabolic side effects of fluoxetine (FLX) by focusing on hepatic lipid
      metabolism. METHODS: Primary mouse hepatocytes were prepared from male mice by
      the two-step perfusion method. The lipid accumulation in primary mouse
      hepatocytes was analyzed via neutral oil staining. And the lipid metabolism
      enzymes were determined with RT-PCR and Western blot. RESULTS: Fluoxetine
      significantly induced the lipid accumulation in primary mouse hepatocytes.
      Moreover, FLX increased the acetyl-CoA carboxylase 1 (ACC1) and fatty acid
      synthase (FAS) expression, which are important enzymes in lipogenesis.
      Oppositely, Fluoxetine significantly decreased the carboxylesterase 3 (CES3) and
      carboxylesterase 1 (CES1) expression, which are related to lipolysis. Further
      study demonstrated FLX-activated SREBP1c, which is one of the most important
      transcription factors conducting coordinated transcriptional regulation of
      lipogenesis gene such as ACC1 and FAS. And the increase of lipogenesis gene
      (ACC1) was abolished by SB203580 but not by pyrrolidine dithiocarbamate (PDTC),
      suggesting through p38-MAPK pathway. CONCLUSION: Fluoxetine induces hepatic lipid
      accumulation via both promotion of the SREBP1c-related lipogenesis and reduction
      of lipolysis in primary mouse hepatocytes.

PMID- 23137030
TI  - DNA damage signaling assessed in individual cells in relation to the cell cycle
      phase and induction of apoptosis.
AB  - Reviewed are the phosphorylation events reporting activation of protein kinases
      and the key substrates critical for the DNA damage signaling (DDS). These DDS
      events are detected immunocytochemically using phospho-specific Abs; flow
      cytometry or image-assisted cytometry provide the means to quantitatively assess
      them on a cell by cell basis. The multiparameter analysis of the data is used to
      correlate these events with each other and relate to the cell cycle phase, DNA
      replication and induction of apoptosis. Expression of gammaH2AX as a possible
      marker of induction of DNA double strand breaks is the most widely studied event
      of DDS. Reviewed are applications of this multiparameter approach to investigate
      constitutive DDS reporting DNA damage by endogenous oxidants byproducts of
      oxidative phosphorylation. Also reviewed are its applications to detect and
      explore mechanisms of DDS induced by variety of exogenous agents targeting DNA
      such as exogenous oxidants, ionizing radiation, radiomimetic drugs, UV light, DNA
      topoisomerase I and II inhibitors, DNA crosslinking drugs and variety of
      environmental genotoxins. Analysis of DDS induced by these agents provides often
      a wealth of information about mechanism of induction and the type of DNA damage
      (lesion) and is reviewed in the context of cell cycle phase specificity, DNA
      replication, and induction of apoptosis or cell senescence. Critically assessed
      is interpretation of the data as to whether the observed DDS events report
      induction of a particular type of DNA lesion.

PMID- 23137034
TI  - Informed consent in direct-to-consumer personal genome testing: the outline of a
      model between specific and generic consent.
AB  - Broad genome-wide testing is increasingly finding its way to the public through
      the online direct-to-consumer marketing of so-called personal genome tests.
      Personal genome tests estimate genetic susceptibilities to multiple diseases and
      other phenotypic traits simultaneously. Providers commonly make use of Terms of
      Service agreements rather than informed consent procedures. However, to protect
      consumers from the potential physical, psychological and social harms associated
      with personal genome testing and to promote autonomous decision-making with
      regard to the testing offer, we argue that current practices of information
      provision are insufficient and that there is a place--and a need--for informed
      consent in personal genome testing, also when it is offered commercially. The
      increasing quantity, complexity and diversity of most testing offers, however,
      pose challenges for information provision and informed consent. Both specific and
      generic models for informed consent fail to meet its moral aims when applied to
      personal genome testing. Consumers should be enabled to know the limitations,
      risks and implications of personal genome testing and should be given control
      over the genetic information they do or do not wish to obtain. We present the
      outline of a new model for informed consent which can meet both the norm of
      providing sufficient information and the norm of providing understandable
      information. The model can be used for personal genome testing, but will also be
      applicable to other, future forms of broad genetic testing or screening in
      commercial and clinical settings.

PMID- 23137033
TI  - Targeting TIM-1 on CD4 T cells depresses macrophage activation and overcomes
      ischemia-reperfusion injury in mouse orthotopic liver transplantation.
AB  - Hepatic injury due to cold storage followed by reperfusion remains a major cause
      of morbidity and mortality after orthotopic liver transplantation (OLT). CD4 T
      cell TIM-1 signaling costimulates a variety of immune responses in allograft
      recipients. This study analyzes mechanisms by which TIM-1 affects liver ischemia
      reperfusion injury (IRI) in a murine model of prolonged cold storage followed by
      OLT. Livers from C57BL/6 mice, preserved at 4 degrees C in the UW solution for 20
      h, were transplanted to syngeneic recipients. There was an early (1 h) increased
      accumulation of TIM-1+ activated CD4 T cells in the ischemic OLTs. Disruption of
      TIM-1 signaling with a blocking mAb (RMT1-10) ameliorated liver damage, evidenced
      by reduced sALT levels and well-preserved architecture. Unlike in controls, TIM-1
      blockade diminished OLT expression of Tbet/IFN-gamma, but amplified IL-4/IL-10/IL
      22; abolished neutrophil and macrophage infiltration/activation and inhibited NF
      kappaB while enhancing Bcl-2/Bcl-xl. Although adoptive transfer of CD4 T cells
      triggered liver damage in otherwise IR-resistant RAG(-/-) mice, adjunctive TIM-1
      blockade reduced Tbet transcription and abolished macrophage activation,
      restoring homeostasis in IR-stressed livers. Further, transfer of TIM-1(Hi) CD4+,
      but not TIM-1(Lo) CD4+ T cells, recreated liver IRI in RAG(-/-) mice. Thus, TIM-1
      expressing CD4 T cells are required in the mechanism of innate immune-mediated
      hepatic IRI in OLTs.

PMID- 23137035
TI  - Chemically doped radial junction characteristics in silicon nanowires.
AB  - We evaluate the boron (B) and phosphorus (P) core-surface codoped radial p-n
      junction characteristics in silicon nanowires (SiNWs) using density functional
      theory calculations. We find that the formation of radial p-n junction is
      energetically favorable. The stability depends on the diameter of SiNWs and the
      dopant concentration. Generally, a higher concentration of B-P pair dopants
      results in a more stable nanowire. More importantly, we predict that the radial p
      n junction can evolve into a Schottky-like junction in relatively highly doped
      SiNWs when the diameter increases, attributing to the change of the core p-doping
      characteristic, that is, the core p-junction becomes metallic, while the n
      junction near the surface remains semiconducting. The interfacial contact between
      the junctions is found to be the key for such change. Our calculated results
      support an experimental observation in SiNW solar cells.

PMID- 23137036
TI  - Skin tumours in the West of Scotland renal transplant population.
AB  - BACKGROUND: Organ transplant recipients have an increased risk of skin cancers. A
      specialist dermatology clinic for renal transplant recipients (RTRs) was
      established in 2005. OBJECTIVES: To analyse the type and incidence of skin
      cancers in prevalent patients in the West of Scotland after renal transplant, and
      to analyse the impact of the time since transplant and the immunosuppression
      regimen. METHODS: Skin cancer data for RTRs attending the transplant dermatology
      clinic over a 38-month period were collected and recorded in the West of Scotland
      electronic renal patient record. Skin cancer data were intrinsically linked to
      each individual's transplant and immunosuppression data. RESULTS: Overall, 610
      patients attended. The median follow-up time from the date of first transplant
      was 10 years. Ninety-three patients (15.2%) had experienced a total of 368 skin
      cancers since transplant, and the prevalence increased with time since
      transplant. Basal cell carcinomas (BCCs) occurred in 74 patients (12.1%) and
      squamous cell carcinomas (SCCs) in 42 patients (6.9%). Three patients (0.5%) had
      experienced a melanoma. The SCC:BCC ratio was 0.7. Survival analysis showed
      significant reduction in the time to develop skin cancer in patients transplanted
      from 1995 onwards (P < 0.0001) and in patients who had been on triple
      immunosuppressant therapy at 1 year after transplant, compared with dual therapy
      (P < 0.0001). CONCLUSIONS: This is the first study of skin cancer in prevalent
      Scottish RTRs. The incidence of skin cancer is high and appears to have a direct
      relationship to the overall burden of immunosuppression. The SCC:BCC ratio, which
      is lower than reports from other centres, deserves further scrutiny.

PMID- 23137037
TI  - Cost-effectiveness of new pneumococcal conjugate vaccines in Turkey: a decision 
      analytical model.
AB  - BACKGROUND: Streptococcus pneumoniae infections, which place a considerable
      burden on healthcare resources, can be reduced in a cost-effective manner using a
      7-valent pneumococcal conjugate vaccine (PCV-7). We compare the cost
      effectiveness of a 13-valent PCV (PCV-13) and a 10-valent pneumococcal non
      typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) with that
      of PCV-7 in Turkey. METHODS: A cost-utility analysis was conducted and a decision
      analytical model was used to estimate the proportion of the Turkish population
      <10 years old that would experience 10 mutually exclusive outcomes over the
      course of 1 year from a perspective of a healthcare system. Model outcomes were
      adjusted according to the population demographics and region-specific serotype
      distribution in Turkey. Health outcomes and direct healthcare costs were
      simulated for PCV-7, PCV-13 and PHiD-CV. RESULTS: PCV-13 and PHiD-CV are
      projected to have a substantial impact on pneumococcal disease in Turkey versus
      PCV-7, with 2,223 and 3,156 quality-adjusted life years (QALYs) and 2,146 and
      2,081 life years, respectively, being saved under a 3+1 schedule. Projections of
      direct medical costs showed that a PHiD-CV vaccination programme would provide
      the greatest cost savings, offering additional savings of US$11,718,813 versus
      PCV-7 and US$8,235,010 versus PCV-13. Probabilistic sensitivity analysis showed
      that PHiD-CV dominated PCV-13 in terms of QALYs gained and cost savings in 58.3%
      of simulations. CONCLUSION: Under the modeled conditions, PHiD-CV would provide
      the most cost-effective intervention for reducing pneumococcal disease in Turkish
      children.

PMID- 23137038
TI  - Cox-Maze III procedure with valvular surgery in an autopneumonectomized patient.
AB  - Destructive pulmonary inflammation can leave patients with only a single
      functional lung, resulting in anatomical and physiological changes that may
      interfere with subsequent cardiac surgeries. Such patients are vulnerable to
      perioperative cardiopulmonary complications. Herein, we report the first case, to
      our knowledge, of an autopneumonectomized patient who successfully underwent a
      modified Cox-Maze III procedure combined with valvular repairs. The three major
      findings in this case can be summarized as follows: (1) a median sternotomy with
      peripheral cannulations, such as femoral cannulations, can provide an optimal
      exposure and prevent the obstruction of vision that may occur as a result of
      multiple cannulations through a median sternotomy; (2) a modified septal incision
      combined with biatrial incisions facilitate adequate exposure of the mitral
      valve; and (3) the aggressive use of intraoperative ultrafiltration may be
      helpful for the perioperative managements as decreasing pulmonary water contents,
      thereby avoiding the pulmonary edema associated with secretion of inflammatory
      cytokines during a cardiopulmonary bypass. We also provide several suggestions
      for achieving similar satisfactory surgical outcomes in patients with a
      comparable condition.

PMID- 23137041
TI  - Increased frequency of single base substitutions in a population of transcripts
      expressed in cancer cells.
AB  - BACKGROUND: Single Base Substitutions (SBS) that alter transcripts expressed in
      cancer originate from somatic mutations. However, recent studies report SBS in
      transcripts that are not supported by the genomic DNA of tumor cells. METHODS: We
      used sequence based whole genome expression profiling, namely Long-SAGE (L-SAGE)
      and Tag-seq (a combination of L-SAGE and deep sequencing), and computational
      methods to identify transcripts with greater SBS frequencies in cancer. Millions
      of tags produced by 40 healthy and 47 cancer L-SAGE experiments were compared to
      1,959 Reference Tags (RT), i.e. tags matching the human genome exactly once.
      Similarly, tens of millions of tags produced by 7 healthy and 8 cancer Tag-seq
      experiments were compared to 8,572 RT. For each transcript, SBS frequencies in
      healthy and cancer cells were statistically tested for equality. RESULTS: In the
      L-SAGE and Tag-seq experiments, 372 and 4,289 transcripts respectively, showed
      greater SBS frequencies in cancer. Increased SBS frequencies could not be
      attributed to known Single Nucleotide Polymorphisms (SNP), catalogued somatic
      mutations or RNA-editing enzymes. Hypothesizing that Single Tags (ST), i.e. tags
      sequenced only once, were indicators of SBS, we observed that ST proportions were
      heterogeneously distributed across Embryonic Stem Cells (ESC), healthy
      differentiated and cancer cells. ESC had the lowest ST proportions, whereas
      cancer cells had the greatest. Finally, in a series of experiments carried out on
      a single patient at 1 healthy and 3 consecutive tumor stages, we could show that
      SBS frequencies increased during cancer progression. CONCLUSION: If the
      mechanisms generating the base substitutions could be known, increased SBS
      frequency in transcripts would be a new useful biomarker of cancer. With the
      reduction of sequencing cost, sequence based whole genome expression profiling
      could be used to characterize increased SBS frequency in patient's tumor and aid
      diagnostic.

PMID- 23137042
TI  - Natural templates for coiled-coil biomaterials from praying mantis egg cases.
AB  - Whereas there is growing interest in producing biomaterials containing coiled
      coils, relatively few studies have made use of naturally occurring fibrous
      proteins. In this study, we have characterized fibrous proteins used by mother
      praying mantises to produce an extensive covering for their eggs called an
      ootheca and demonstrate the production of artificial ootheca using recombinantly
      produced proteins. Examination of natural oothecae by infrared spectroscopy and
      solid-state nuclear magnetic resonance revealed the material to consist of
      proteins organized predominately as coiled-coils. Two structural proteins, Mantis
      Fibroin 1 and Mantis Fibroin 2, were identified in ootheca from each of three
      species. Between species, the primary sequences of both proteins had diverged
      considerably, but other features were tightly conserved, including low molecular
      weight, high abundance of Ala, Glu, Lys, and Ser, and a triblock-like
      architecture with extensive central coiled-coil domain. Mantis fibroin
      hydrophobic cores had an unusual composition containing high levels of alanine
      and aromatic residues. Recombinantly produced mantis fibroins folded into coiled
      coils in solution and could be fabricated into solid materials with high coiled
      coil content. The structural features of mantis fibroins and their
      straightforward recombinant production make them promising templates for the
      production of coiled-coil biomimetics materials.

PMID- 23137043
TI  - Clinical indicators in surgery: a critical review of the Australian experience.
AB  - BACKGROUND: A set of clinical measures (indicators), developed by an Australian
      Council on Healthcare Standards (ACHS) and Royal Australasian College of Surgeons
      (RACS) working party, was introduced into the accreditation programme in 1997.
      Although early qualitative and quantitative reporting by health-care
      organizations (HCOs) reflected their value in stimulating change, the number of
      HCOs reporting data on this set of clinical indicators (CIs) has declined,
      despite an increase in the number of HCOs reporting data on the CIs programme
      overall. Possible reasons for this decline were sought. METHODS: A retrospective
      review of prospectively collected surgical CI data was performed, a national
      survey of stakeholders in the ACHS programme was conducted and a comparison was
      made with published international data. RESULTS: From a maximum of 247 HCOs
      reporting data in 2002, the number fell to 168 by 2011. While favourable trends
      were evident with some CIs, for example, a decline in the rate of negative
      histology in childhood appendicectomy and in the rate of in-hospital infection in
      total hip joint replacement, there was minimal change with many of the CIs,
      suggesting limited responsiveness as measures of care. In the national survey,
      stakeholder's response was positive overall, but there was a requirement for
      regular review of CIs. Although some colleges viewed the CIs as simplistic and
      not reliable, comparisons with similar measures available in the international
      literature were favourable. CONCLUSIONS: Possible reasons for the declining
      number of HCOs reporting surgical CI data are a lack of a recent revision of the
      CIs and a lack of engagement of clinicians from the RACS. Revision of the
      surgical CI set is required.

PMID- 23137044
TI  - Do lower cuff pressures reduce damage to the tracheal mucosa? A scanning electron
      microscopy study in neonatal pigs.
AB  - BACKGROUND: Modern high volume-low pressure (HVLP) endotracheal tubes (ETT) cuffs
      can seal the trachea using baseline cuff pressures (CP) lower than peak
      inspiratory airway pressures (PIP). The aim of the study was to determine whether
      this technique reduces the damage to the tracheal mucosa compared to constant CP
      of 20 cmH(2)O. METHODS: Eighteen piglets were intubated with an ID 4.0 mm HVLP
      cuffed ETT (Microcuff PET) and artificially ventilated with 20 cmH(2)O PIP and 5
      cmH(2)O PEEP. Animals were randomly allocated to two groups of CP: group A (just
      seal; n = 9) and group B (20 cmH(2)O; n = 9), controlled constantly with a
      manometer during the following 4-h study period under sevoflurane anesthesia.
      After euthanasia, cuff position was marked in situ. Damage in the cuff region was
      evaluated with scanning electron microscopy (SEM) examination by grading of
      mucosal damage and by estimating percentage of intact mucosal area both by a
      blinded observer. RESULTS: Maximal CP to seal the trachea in group A ranged from
      12 to 18 cmH(2)O (median: 14 cmH(2)O). Using a mixed effects model approach, the
      estimated mean effect of group B vs group A was an increase of 17.9% (SE 8.1%)
      higher proportion of pictures with an area of at least 5% intact mucosa (P =
      0.042). CONCLUSION: Minimal sealing pressures with cyclic pressure changes from
      CP did not result in decreased damage to the tracheal mucosa compared to constant
      CP of 20 cmH(2)O in this short-term animal trial.

PMID- 23137045
TI  - Intense focused ultrasound preferentially stimulates subcutaneous and focal
      neuropathic tissue: preliminary results.
AB  - OBJECTIVE: Potential peripheral sources of pain from subcutaneous tissue can
      require invasive evocative tests for their localization and assessment. Here, we
      describe studies whose ultimate goal is development of a noninvasive evocative
      test for subcutaneous, painful tissue. DESIGN: We used a rat model of a focal and
      subcutaneous neuroma to test the hypothesis that intense focused ultrasound can
      differentiate focal and subcutaneous neuropathic tissue from control tissue. To
      do so, we first applied intense focused ultrasound (2 MHz, with individual pulses
      of 0.1 second in duration) to the rat's neuroma while the rat was under light
      anesthesia. We started with low values of intensity, which we increased until
      intense focused ultrasound stimulation caused the rat to reliably flick its paw.
      We then applied that same intense focused ultrasound protocol to control tissue
      away from the neuroma and assayed for the rat's response to that stimulation.
      RESULTS: Intense focused ultrasound of sufficient strength (I(SATA) of 600 +/-
      160 W/cm(2) ) applied to the neuroma caused the rat to flick its paw, while the
      same intense focused ultrasound applied millimeters to a centimeter away failed
      to induce a paw flick. CONCLUSION: Successful stimulation of the neuroma by
      intense focused ultrasound required colocalization of the neuroma and intense
      focused ultrasound supporting our hypothesis.

PMID- 23137047
TI  - Reversible and cyclical transformations between solid and hollow nanostructures
      in confined reactions of manganese oxide and silica within nanosized spheres.
AB  - Annealing of MnO@SiO(2) nanospheres in a reducing gas environment resulted in the
      transformation of the core-shell structure into a hollow structure as a result of
      outward diffusion of MnO species into the thermodynamically more stable silicate
      phase. When the hollow silicate nanospheres were oxidized, the interior cavities
      were refilled with a Mn(3)O(4) phase segregated from the silicate phase, and the
      hollow structure reverted to the initial core-shell structure. More
      interestingly, when catalytically active Pt nanocrystals were introduced into the
      manganese oxide/silica system, the Mn(3)O(4) was readily reduced to the
      chemically reactive MnO, even at low temperature, which enabled reconversion of
      the solid nanospheres with a Mn(3)O(4) core to hollow nanostructures during
      reductive annealing. Therefore, when MnO@SiO(2)/Pt(II) nanospheres were subjected
      to an oxidation/reduction cycle by repeatedly switching the flowing gas between
      air and hydrogen, the nanospheres underwent a reversible change between solid and
      hollow structures, depending on the gas environment. The solid-to-hollow-to-solid
      transformation was successfully cycled many times simply by repeatedly switching
      the flowing gas during annealing.

PMID- 23137046
TI  - Assessing the potential to use neurocognition to predict who is at risk for
      developing bipolar disorder: a review of the literature.
AB  - INTRODUCTION: The importance of early intervention strategies has recently been
      recognised in the field of psychiatry. Although early intervention strategies in
      schizophrenia have been extensively studied, recent efforts to identify
      individuals who are at increased risk for other disorders, such as bipolar
      disorder, have gained significant interest. There is some available data to
      suggest that cognitive deficits may precede the onset of mania; therefore, it
      would be beneficial to identify cognitive predictors of bipolar disorder in an
      effort to facilitate early intervention. METHODS: We conducted a literature
      review of conscript, cohort, high-risk, family-based and first-episode mania
      studies that assessed neurocognition in order to ascertain potential cognitive
      predictors of bipolar disorder. RESULTS: There is little evidence that
      individuals at risk for bipolar disorder exhibit deficits in global measures of
      neurocognition, such as IQ. However, deficits in specific neurocognitive domains,
      including verbal memory and executive function, appear to represent potential
      predictors of bipolar disorder. CONCLUSIONS: These conclusions are preliminary;
      however, they provide a starting point for future work. Additional efforts
      towards understanding both the clinical and cognitive prodrome will be important
      in elucidating the pathophysiology of bipolar disorder.

PMID- 23137048
TI  - 1H and 13C NMR assignments for the cyanine dyes SYBR Safe and thiazole orange.
AB  - Analysis of (1)H and (13)C NMR and mass spectral data for the fluorescent nucleic
      acid stain SYBR Safe indicates that it contains a cyanine-based cationic core
      structure identical to thiazole orange. The difference between these two
      compounds is the type of N-substitution on the quinolinium ring system (SYBR
      Safe, n-Pr; thiazole orange, Me). The (1)H and (13)C NMR resonances for both
      compounds were assigned on the basis of one- and two-dimensional (COSY, ROESY,
      HSQC, and HMBC) experiments. The preferred conformation of these compounds was
      computed by ab initio methods and found to be consistent with the NMR data.

PMID- 23137049
TI  - Metformin and reduced risk of hepatocellular carcinoma in diabetic patients: a
      meta-analysis.
AB  - OBJECTIVES: Recent epidemiological studies suggest that metformin treatment may
      reduce the risks of cancer and overall cancer mortality among patients with
      diabetes mellitus (DM). However, data on hepatocellular carcinoma (HCC) are very
      limited and inconsistent. This meta-analysis was designed to pool data currently
      available to determine the association between metformin use and HCC among
      diabetic patients. METHODS: The Medline and Embase databases were searched to
      identify the relevant studies between January 1966 and December 2011. The overall
      analysis was derived using a random-effects meta-analysis model (DerSimonian and
      Laird method). Subgroup analysis was performed to explore the source of
      heterogeneity and validate the results from overall analysis. The Newcastle
      Ottawa Quality assessment scales were adopted for quality assessment; Begg's
      funnel plot and Egger's regression asymmetry test were used to detect the
      publication bias. RESULTS: A total of seven studies were identified, including
      three cohort studies and four case-control studies. Based on the available data,
      the overall prevalence of HCC was 3.40% (562/16,549) in DM patients. The overall
      analysis showed a significantly reduced risk of HCC in metformin users versus
      nonusers in diabetic patients (relative risk (RR) 0.24, 95% confidence interval
      (CI) 0.13-0.46, p < 0.001). Fifteen subgroup analyses were performed, and most of
      them (12/15 = 80%) provided supporting evidence for the results of overall
      analysis. Begg's (Z = -0.15, p = 0.8819) and Egger's test (t = -0.79, p = 0.468)
      showed no significant risk of having a publication bias. CONCLUSION: Metformin
      treatment was associated with reduced risk of HCC in diabetic patients. To
      clarify this relationship, more high-quality studies are required.

PMID- 23137050
TI  - Point accuracy of interstitial continuous glucose monitoring during exercise in
      type 1 diabetes.
AB  - BACKGROUND: Previous studies of aerobic exercise have found lower sensor accuracy
      during exercise. Whether or not resistance exercise would also be associated with
      lower sensor accuracy has not yet been examined. This study sought to investigate
      the accuracy of continuous glucose monitoring sensor values at rest, during
      aerobic exercise, and during resistance exercise. SUBJECTS AND METHODS: Twelve
      individuals with type 1 diabetes performed 45 min of aerobic exercise, resistance
      exercise, or no exercise/rest followed by 60 min of recovery while monitored by
      continuous glucose monitoring systems. RESULTS: Sensors underestimated plasma
      glucose to the greatest extent during rest (-1.29 +/- 1.39 mmol/L, P<0.001) and
      resistance exercise (-0.71 +/- 1.35 mmol/L, P<0.001) and least during aerobic
      exercise (-0.11 +/- 1.71 mmol/L, P=0.416). CONCLUSIONS: Optimal accuracy observed
      with aerobic exercise might arise from augmented blood flow better equilibrating
      plasma and interstitial fluid or from the combination of systematic sensor
      underestimation and sensor lag time.

PMID- 23137051
TI  - Chemoprevention of 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster cheek
      pouch carcinogenesis by a 5-lipoxygenase inhibitor, garcinol.
AB  - Our previous studies have shown that aberrant arachidonic acid metabolism,
      especially the 5-lipoxygenase (5-Lox) pathway, is involved in oral carcinogenesis
      and can be targeted for cancer prevention. To develop potent topical agents for
      oral cancer chemoprevention, 5 known 5-Lox inhibitors from dietary and synthetic
      sources (Zileuton, ABT-761, licofelone, curcumin, and garcinol) were evaluated in
      silico for their potential efficacy. Garcinol, a polyisoprenylated benzophenone
      from the fruit rind of Garcinia spp., was found to be a promising agent based on
      the calculation of a theoretical activity index. Computer modeling showed that
      garcinol well fit the active site of 5-Lox, and potentially inhibited enzyme
      activity through interactions between the phenolic hydroxyl groups and the non
      heme catalytic iron. In a short-term study on 7,12-dimethylbenz[a]anthracene
      (DMBA)-treated hamster cheek pouch, topical garcinol suppressed leukotriene B4
      (LTB4) biosynthesis and inhibited inflammation and cell proliferation in the oral
      epithelium. In a long-term carcinogenesis study, topical garcinol significantly
      reduced the size of visible tumors, the number of cancer lesions, cell
      proliferation, and LTB4 biosynthesis. These results demonstrated that topical
      application of a 5-Lox inhibitor, garcinol, had chemopreventive effect on DMBA
      induced hamster cheek pouch carcinogenesis.

PMID- 23137052
TI  - Multidisciplinary approach to epizootiology and pathogenesis of bat rabies
      viruses in the United States.
AB  - Zoonotic disease surveillance is typically initiated after an animal pathogen has
      caused disease in humans. Early detection of potentially high-risk pathogens
      within animal hosts may facilitate medical interventions to cope with an emerging
      disease. To effectively spillover to a novel host, a pathogen may undergo genetic
      changes resulting in varying transmission potential in the new host and
      potentially to humans. Rabies virus (RABV) is one model pathogen to consider for
      studying the dynamics of emerging infectious diseases under both laboratory and
      field conditions. The evolutionary history of RABV is characterized by regularly
      documented spillover infections and a series of notable host shifts. Within this
      context, enhanced field surveillance to improve detection of spillover infections
      will require validated techniques to non-invasively differentiate infected from
      non-infected individuals. In this study, we evaluate the use of infrared
      thermography to detect thermal changes associated with experimental RABV
      infection in big brown bats (Eptesicus fuscus) in a captive colony. Our results
      indicated that 62% of rabid bats had detectable facial temperature decreases (
      4.6 degrees C, SD +/- 2.5) compared with pre-inoculation baseline values. These
      data suggest potential utility for discriminating rabid bats in natural field
      settings. In addition, focusing upon RABV circulating in the United States
      between 2008 and 2011, we confirmed spillover events of bat RABV among carnivores
      and identified cross-species transmission events caused by four lineages of RABV
      associated with insectivorous bats. Additionally, our analysis of RABV
      glycoprotein sequences identified substitutions in antigenic sites that may
      affect neutralizing activity associated with monoclonal antibodies proposed for
      use in human post-exposure prophylaxis. This study provides a glimpse into RABV
      pathobiology and spillover dynamics among and between bats and a variety of
      mesocarnivores.

PMID- 23137053
TI  - Kinetic study of olive oil degradation monitored by fourier transform infrared
      spectrometry. Application to oil characterization.
AB  - A new approach for the determination of kinetic parameters of the cis/trans
      isomerization during the oxidation process of 24 virgin olive oils belonging to 8
      different varieties is presented. The accelerated process of degradation at 100 
      degrees C was monitored by recording the Fourier transform infrared spectra. The
      parameters obtained confirm pseudo-first-order kinetics for the degradation of
      cis and the appearance of trans double bonds. The kinetic approach affords the
      induction time and the rate coefficient; these parameters are related to the
      fatty acid profile of the fresh olive oils. The data obtained were used to
      compare the oil stability of the samples with the help of multivariate
      statistical techniques. Fatty acid allowed a classification of the samples in
      five groups, one of them constituted by the cultivars with higher stability.
      Meanwhile, the kinetic parameters showed greater ability for the characterization
      of olive oils, allowing the classification in seven groups.

PMID- 23137054
TI  - Knowledge of patients' visual experience during cataract surgery: a survey of eye
      doctors in Karachi, Pakistan.
AB  - BACKGROUND: Several recent studies have recommended that ophthalmologists must be
      aware of the visual sensations (and their associated anxiety/fear) experienced by
      patients undergoing cataract surgery. We assessed the knowledge of a group of eye
      doctors in Pakistan regarding these phenomena. METHODS: This was a cross
      sectional survey. Eye doctors (ophthalmologists, residents and medical officers)
      attending the Ophthalmological Society of Pakistan Annual Conference 2011, in
      Karachi were invited to participate in the study. A self-administered structured
      questionnaire was used to examine their knowledge of visual sensations and their
      associated anxiety/fear experienced by patients during cataract surgery. Simple
      frequencies and proportions were calculated to describe the data. RESULTS: A
      total of 150 ophthalmologists, residents and medical officers were invited to
      participate in the study. Of these, 68 (45.3%) responded. The mean age (+/-SD) of
      the participants was 42.9 (13.2) years. The proportion of participants who
      thought that patients could experience visual sensations during cataract surgery
      under regional anaesthesia was 89.7% and that under topical anaesthesia was
      73.5%. The most frequently cited sensations included: light perception, changes
      in light brightness, movements, instruments and surgeon's hands or fingers.The
      eye doctors estimated that 38.9% and 64.3% patients would see at least something
      during cataract surgery under regional anaesthesia and topical anaesthesia,
      respectively. They also believed that 24.2%-36.9% of patients may experience
      anxiety/fear as a result of visual sensations during such surgery. Approximately
      half of the eye doctors did not think that retained vision was a source of fear
      or anxiety for the patients. While most of them acknowledged the importance of
      preoperative counselling in helping to alleviate such fear/anxiety, the majority
      of them did not regularly counsel their patients on what to expect during the
      surgery. CONCLUSION: Our study reveals that a significant proportion of eye
      doctors do not have adequate knowledge of the visual phenomenon and their
      associated anxiety or fear, that patients can experience during cataract surgery.
      Targeted educational interventions are needed to increase awareness of this
      phenomenon among eye care professionals.

PMID- 23137055
TI  - The impacts of AIDS movements on the policy responses to HIV/AIDS in Brazil and
      South Africa: a comparative analysis.
AB  - Brazil and South Africa were among the first countries profoundly impacted by the
      HIV/AIDS epidemic and had similar rates of HIV infection in the early 1990s.
      Today, Brazil has less than 1% adult HIV prevalence, implemented treatment and
      prevention programmes early in the epidemic, and now has exemplary HIV/AIDS
      programmes. South Africa, by contrast, has HIV prevalence of 18% and was, until
      recently, infamous for its delayed and inappropriate response to the HIV/AIDS
      epidemic. This article explores how differing relationships between AIDS
      movements and governments have impacted the evolving policy responses to the AIDS
      epidemic in both countries, including through AIDS programme finance, leadership
      and industrial policy related to production of generic medicines.

PMID- 23137056
TI  - Why do two pi-electron four-membered Huckel rings pucker?
AB  - Notwithstanding their two (i.e., 4n + 2) pi electrons, four-membered ring
      systems, 1-4, favor puckered geometries (1a-4a) despite the reduction in vicinal
      pi overlap and in the ring atom bond angles. This nonplanar preference is due to
      sigma -> pi* hyperconjugative interactions across the ring (A) rather than to
      partial 1,3-bonding (B). Electronegative substituents (e.g., F in C(4)F(4)(2+))
      reduce the sigma -> pi* electron delocalization, and planar geometries result. In
      contrast, electropositive groups (e.g., SiH(3) in C(4)(SiH(3))(4)(2+)) enhance
      hyperconjugation and increase the ring inversion barriers substantially.

PMID- 23137057
TI  - Mitochondria and chloroplasts as the original sites of melatonin synthesis: a
      hypothesis related to melatonin's primary function and evolution in eukaryotes.
AB  - Mitochondria and chloroplasts are major sources of free radical generation in
      living organisms. Because of this, these organelles require strong protection
      from free radicals and associated oxidative stress. Melatonin is a potent free
      radical scavenger and antioxidant. It meets the criteria as a mitochondrial and
      chloroplast antioxidant. Evidence has emerged to show that both mitochondria and
      chloroplasts may have the capacity to synthesize and metabolize melatonin. The
      activity of arylalkylamine N-acetyltransferase (AANAT), the reported rate
      limiting enzyme in melatonin synthesis, has been identified in mitochondria, and
      high levels of melatonin have also been found in this organelle. From an
      evolutionary point of view, the precursor of mitochondria probably is the purple
      nonsulfur bacterium, particularly, Rhodospirillum rubrum, and chloroplasts are
      probably the descendents of cyanobacteria. These bacterial species were
      endosymbionts of host proto-eukaryotes and gradually transformed into cellular
      organelles, that is, mitochondria and chloroplasts, respectively, thereby giving
      rise to eukaryotic cells. Of special importance, both purple nonsulfur bacteria
      (R. rubrum) and cyanobacteria synthesize melatonin. The enzyme activities
      required for melatonin synthesis have also been detected in these primitive
      species. It is our hypothesis that mitochondria and chloroplasts are the original
      sites of melatonin synthesis in the early stage of endosymbiotic organisms; this
      synthetic capacity was carried into host eukaryotes by the above-mentioned
      bacteria. Moreover, their melatonin biosynthetic capacities have been preserved
      during evolution. In most, if not in all cells, mitochondria and chloroplasts may
      continue to be the primary sites of melatonin generation. Melatonin production in
      other cellular compartments may have derived from mitochondria and chloroplasts.
      On the basis of this hypothesis, it is also possible to explain why plants
      typically have higher melatonin levels than do animals. In plants, both
      chloroplasts and mitochondria likely synthesize melatonin, while animal cells
      contain only mitochondria. The high levels of melatonin produced by mitochondria
      and chloroplasts are used to protect these important cellular organelles against
      oxidative stress and preserve their physiological functions. The superior
      beneficial effects of melatonin in both mitochondria and chloroplasts have been
      frequently reported.

PMID- 23137060
TI  - Lysosomal storage disorder in non-immunological hydrops fetalis (NIHF): more
      common than assumed? Report of four cases with transient NIHF and a review of the
      literature.
AB  - BACKGROUND: Lysosomal storage disorders (LSD) are a rare cause of non
      immunological hydrops fetalis (NIHF) and congenital ascites. The reported
      incidence is about 1%. The incidence of idiopathic NIHF is estimated to be about
      18%. PATIENTS AND METHODS: We report four cases with transient hydrops fetalis
      resulting from LSD and performed a literature review on LSD with NIHF and
      congenital ascites in combination. RESULTS: At present, 12 different LSDs are
      described to be associated with NIHF or congenital ascites. Most patients had a
      family history of NIHF, where the preceding sibling had not been examined. A
      diagnostic approach to the fetus with NIHF due to suspected LSD either in utero
      or postnatal is suggested. Transient forms of NIHF and/or ascites in association
      with MPS IVA, MPS VII and NPC are described for the first time in this
      publication. CONCLUSIONS: LSD should be considered in transient hydrops.
      Enzymatic studies in chorionic villous sample or amniotic cultured cells, once
      the most common conditions associated with fetal ascites or hydrops have been
      ruled out, are important. This paper emphasizes the fact that LSD is
      significantly higher than the estimated 1% in previous studies, which is
      important for genetic counseling as there is a high risk of recurrence and the
      availability of enzyme replacement therapy for an increasing number of LSD.

PMID- 23137062
TI  - Should cities invest in sheltering-in-place measures against chlorine truck
      attacks by terrorists?
AB  - After an intentional release of chlorine in an office district, public responses
      such as sheltering-in-place could save many lives if rapid enough. However,
      previous work does not estimate how fast and effective such responses would be
      for several possible investments in attack detection, public alert, and building
      ventilation, nor whether such measures would be cost effective. We estimate
      public response times with investment options in place, and resulting changes in
      fatalities as well as system costs, including false alarm costs, and cost
      effectiveness in terms of cost per net death avoided. The measures do have life
      saving potential, especially if all response times are at or near the lower
      limits of the ranges assumed in this article. However, due to uncertainties, it
      is not clear that responses would be rapid enough to save many people. In some
      cases total fatalities would increase, since sheltering after chlorine vapor has
      already entered buildings can increase occupants' chlorine exposure. None of the
      options considered have median cost per statistical life saved meeting a cost
      effectiveness threshold of $6.5 million across all of the chlorine exposure dose
      response and ingress-delay models considered here, even if there were one attack
      per year in the area covered by the system. Given these and other issues
      discussed in this article, at this point investments to improve sheltering-in
      place capability appear not to be robust strategies for reducing fatalities from
      chlorine attack in an office district.

PMID- 23137061
TI  - Chronic exposure of renal stem cells to inorganic arsenic induces a cancer
      phenotype.
AB  - Inorganic arsenic in the drinking water is a multisite human carcinogen that
      potentially targets the kidney. Recent evidence also indicates that developmental
      arsenic exposure impacts renal carcinogenesis in humans and mice. Emerging theory
      indicates that cancer may be a disease of stem cells (SCs) and that there are
      abundant active SCs during early life. Therefore, we hypothesized that inorganic
      arsenic targets SCs, or partially differentiated progenitor cells (PCs), for
      oncogenic transformation. Thus, a rat kidney SC/PC cell line, RIMM-18, was
      chronically exposed to low-level arsenite (500 nM) for up to 28 weeks. Multiple
      markers of acquired cancer phenotype were assessed biweekly during arsenic
      exposure, including secreted matrix metalloproteinase (MMP) activity,
      proliferation rate, colony formation in soft agar, and cellular invasiveness.
      Arsenic exposure by 10 weeks and after also induced marked and sustained
      increases in colony formation, indicative of the loss of contact inhibition, and
      increased invasiveness, both cancer cell characteristics. Compared to the passage
      matched control, chronic arsenic exposure caused exposure-duration dependent
      increases in secreted MMP-2 and MMP-9 activity, Cox-2 expression, and more rapid
      proliferation (all >2-fold), characteristics typical of cancer cells.
      Dysregulation of SC maintenance genes and signaling pathways are common during
      oncogenesis. During arsenite exposure, expression of several genes associated
      with normal kidney development and SC regulation and differentiation (i.e., Wt-1,
      Wnt-4, Bmp-7, etc.) were aberrantly altered. Arsenic-exposed renal SCs produced
      more nonadherent spheroid bodies that grew much more aggressively in Matrigel,
      typical of cancer SCs (CSCs). The transformed cells also showed gene
      overexpression typical of renal SCs/CSCs (CD24, Osr1, Ncam) and arsenic
      adaptation such as overexpression of Mt-1, Mt2, Sod-1, and Abcc2. These data
      suggest that inorganic arsenic induced an acquired cancer phenotype in vitro in
      these rat kidney SCs potentially forming CSCs and, consistent with data in vivo,
      indicate that these multipotent SCs may be targets of arsenic during renal
      carcinogenesis. 

PMID- 23137063
TI  - Side-by-side comparison of photodynamic therapy and pulsed-dye laser treatment of
      port-wine stain birthmarks.
AB  - BACKGROUND: Pulsed-dye laser (PDL)-mediated photothermolysis is the current
      standard treatment for port-wine stain (PWS) birthmarks. Vascular-targeted
      photodynamic therapy (PDT) might be an alternative for the treatment of PWS.
      OBJECTIVES: To compare clinical outcomes of PDT and PDL treatment of PWS.
      METHODS: Two adjacent flat areas of PWS lesions were selected from each of 15
      patients (two male and 13 female; age 11-36 years) and randomly assigned to
      either single-session PDL or PDT. PDL was delivered using a 585-nm pulsed laser.
      PDT was carried out with a combination of haematoporphyrin monomethyl ether
      (HMME) and a low-power copper vapour laser (510.6 and 578.2 nm). Clinical
      outcomes were evaluated colorimetrically and visually during follow-up. RESULTS:
      A total of nine red PWS lesions and six purple PWS lesions were treated. For red
      PWS, colorimetric assessment showed that the blanching rates of PDL and PDT at 2
      months ranged from -11% to 24% and 22% to 55%, respectively. For purple PWS,
      blanching rates of PDL and PDT ranged from 8% to 33% and 30% to 45%,
      respectively. Overall, there was a significant difference between the blanching
      effect of single-session PDL treatment and a single-session PDT treatment.
      CONCLUSIONS: This side-by-side comparison demonstrates that PDT is at least as
      effective as PDL and, in some cases, superior. The true value of PDT for the
      treatment of PWS deserves further investigation.

PMID- 23137064
TI  - An unexpected cause of cardiac arrest during laparoscopy in an infant with
      supravalvar aortic stenosis.
AB  - Patients with congenital supravalvar aortic stenosis (SVAS) with associated
      biventricular outflow tract obstruction and coronary artery abnormalities have a
      tenuous myocardial oxygen supply/demand relationship. They are at increased risk
      of acute myocardial ischemia and sudden death, especially during anesthesia.
      Furthermore, resuscitation during cardiac arrest is frequently unsuccessful. We
      report a case of perioperative cardiac arrest due to an unexpected cause in a 2
      month old with SVAS during a laparoscopic Nissen fundoplication.

PMID- 23137065
TI  - Moving from ideas to action - developing health financing systems towards
      universal coverage in Africa.
AB  - BACKGROUND: Accelerating progress towards universal coverage in African
      countries calls for concrete actions that reinforce social health protection
      through establishment of sustainable health financing mechanisms. In order to
      explore possible pathways for moving past the existing obstacles, panel
      discussions were organized on health financing bringing together Ministers of
      health and Ministers of finance with the objective of creating a discussion space
      where the different perspectives on key issues and needed actions could meet.
      This article presents a synthesis of panel discussions focusing on the identified
      challenges and the possible solutions. The overview of this paper is based on the
      objectives and proceedings of the panel discussions and relies on the observation
      and study of the interaction between the panelists and on the discourse used.
      SUMMARY: The discussion highlighted that a large proportion of the African
      population has no access to needed health services with significant reliance on
      direct out of pocket payments. There are multiple obstacles in making prepayment
      and pooling mechanisms operational. The relatively strong political commitment to
      health has not always translated into more public spending for health. Donor
      investment in health in low income countries still falls below commitments. There
      is need to explore innovative domestic revenue collection mechanisms. Although
      inadequate funding for health is a fundamental problem, inefficient use of
      resources is of great concern. There is need to generate robust evidence focusing
      on issues of importance to ministry of finance. The current unsatisfactory state
      of health financing was mainly attributed to lack of clear vision; evidence based
      plans and costed strategies. DISCUSSION: Based on the analysis of discussion
      made, there are points of convergence and divergence in the discourse and
      positions of the two ministries. The current blockage points holding back budget
      allocations for health can be solved with a more evidence based approach and
      dialogue based on a clear vision and costed strategic plan articulated by the
      ministry of health. Improving health in Africa is a driver for long-term economic
      growth and development and this is the reason why the ministries of health and
      finance will need to find common ground on how to create policy coherence and how
      to articulate their respective objectives.

PMID- 23137066
TI  - Off-label use of recombinant factor VIIa in two tertiary hospitals in Queensland.
AB  - BACKGROUND: Recombinant factor VIIa (rFVIIa) is used for many off-label
      indications without high quality evidence to support its efficacy. The aim of
      this study was to determine indications for use of off-label rFVIIa, efficacy and
      safety, and adherence to institutional guidelines. METHODS: We performed a
      retrospective review of off-label rFVIIa at two tertiary hospitals from 2007 to
      2010. RESULTS: One hundred forty-five administrations were identified and
      analysed. Haemorrhage associated with cardiac surgery made up one-third of all
      rFVIIa usage, with trauma (20%) and other surgery (11%) the next most frequent
      indications. Compared with all others, cardiac surgery patients were older (60.0
      years versus 47.4 years, P < 0.001) and had lower pre-rFVIIa transfusion
      requirements, a higher subjective response rate (88% versus 46%, P < 0.001) and
      lower mortality rates (6.1% versus 33%, P < 0.001), but higher rates of arterial
      thrombormbolic events (16.7% versus 2.1%, P = 0.002). Most patients received only
      one or two doses (n = 137; 95%), with no subject receiving a third or subsequent
      dose having an appreciable reduction in bleeding. Only a small number of patients
      (n = 15; 10.3%) had rFVIIa administered in accordance with our institutions'
      guidelines. CONCLUSION: Patients administered rFVIIa for haemorrhage not
      associated with cardiac surgery were severely unwell. Despite lack of evidence,
      administration of rFVIIa may be justified by the high mortality rate, but more
      than two doses are unlikely to provide further benefit. The high rate of arterial
      thromboembolism in cardiac surgical patients raises risk-benefit considerations.
      Adherence to our institutions' guidelines was poor.

PMID- 23137067
TI  - Cardiac troponin T before and after kidney transplantation: determinants and
      implications for posttransplant survival.
AB  - Pretransplant cardiac troponin T(cTnT(pre) ) is a significant predictor of
      survival postkidney transplantation. We assessed correlates of cTnT levels pre-
      and posttransplantation and their relationship with recipient survival. A total
      of 1206 adult recipients of kidney grafts between 2000 and 2010 were included.
      Pretransplant cTnT was elevated (>=0.01 ng/mL) in 56.4%. Higher cTnT(pre)  was
      associated with increased risk of posttransplant death/cardiac events independent
      of cardiovascular risk factors. Elevated cTnT(pre)  declined rapidly
      posttransplant and was normal in 75% of recipients at 3 weeks and 88.6% at 1
      year. Elevated posttransplant cTnT was associated with reduced patient survival
      (cTnT(3wks) : HR = 5.575, CI 3.207-9.692, p < 0.0001; cTnT(1year) : 3.664, 2.129
      6.305, p < 0.0001) independent of age, diabetes, pretransplant dialysis, heart
      disease and allograft function. Negative/positive predictive values for high
      cTnT(3wks)  were 91.4%/50% respectively. Normalization of cTnT posttransplant was
      associated with reduced risk. Variables related to elevated cTnT posttransplant
      included pretransplant diabetes, older age, time on dialysis, high cTnT(pre)  and
      lower graft function. Patients with delayed graft function and those with GFR <
      30 mL/min at 3 weeks were more likely to have an elevated cTnT(3wks)  and
      remained at high risk. When allografts restore sufficient kidney function cTnT
      normalizes and patient survival improves. Lack of normalization of cTnT
      posttransplant identifies a group of individuals with high risk of death/cardiac
      events.

PMID- 23137068
TI  - Luminescent, enantiopure, phenylatopyridine iridium-based coordination capsules.
AB  - The first molecular capsule based on an [Ir(ppy)(2)](+) unit (ppy = 2
      phenylatopyridine) has been prepared. Following the development of a method to
      resolve rac-[(Ir(ppy)(2)Cl)(2)] into its enantiopure forms, homochiral Ir(6)L(4)
      octahedra where obtained with the tritopic 1,3,5-tricyanobenzene. Solution
      studies and X-ray diffraction show that these capsules encapsulate four of the
      six associated counteranions and that these can be exchanged for other anionic
      guests. Initial photophysical studies have shown that an ensemble of weakly
      coordinating ligands can lead to luminescence not present in comparable
      mononuclear systems.

PMID- 23137069
TI  - Missing information in birth certificates in Brussels after reinforcement of data
      collection, and variation according to immigration status. A population-based
      study.
AB  - BACKGROUND: A problem repeatedly reported in birth certificate data is the
      presence of missing data. In 2008, a Centre for Perinatal Epidemiology was
      created inter alia to assist the Health Departments of Brussels-Capital City
      Region to check birth certificates. The purpose of this study is to assess the
      changes brought by the Centre in terms of completeness of data registration for
      the entire population and according to immigration status. METHODS: Birth
      certificates from the birth registry of 2008 and 2009 of Brussels were
      considered. We evaluated the initial missing information in January 2008
      (baseline situation) and the corresponding rate at the end of 2008 after oral and
      written information had been given to the city civil servants and health
      providers. The data were evaluated again at the end of 2009 where no
      reinforcement rules were adopted. We also measured residual missing data after
      correction in socio-economic and medical data, for the entire population and
      according to maternal nationality of origin. Changes in registration of
      stillbirths were estimated by comparison to 2007 baseline data, and all multiple
      births were checked for complete identification of pairs. RESULTS: Missing
      information initially accounted for 64.0%, 20.8% and 19.5% of certificates in
      January 2008, December 2008, and 2009 respectively. After correction with lists
      sent back to the hospitals or city offices, the mean residual missing data rate
      was 2.1% in 2008 and 0.8% in 2009. Education level and employment status were
      missing more often in immigrant mothers compared to Belgian natives both in 2008
      and 2009. Mothers from Sub-Saharan Africa had the highest missing rate of socio
      economic data. The stillbirth rate increased from 4.6 0/00 in 2007 to 8.2 0/00 in
      2009. All twin pairs were identified, but early loss of a co-twin before 22 weeks
      was rarely reported. CONCLUSIONS: Reinforcement of data collection was associated
      with a decrease of missing information. The residual missing data rate was very
      low. The stillbirth rate was also improved but the early loss of a co-twin before
      22 weeks seems to remain underreported.

PMID- 23137070
TI  - Prognostic significance of rituximab and radiotherapy for patients with primary
      mediastinal large B-cell lymphoma receiving doxorubicin-containing chemotherapy.
AB  - Abstract The aim of this study was to evaluate the prognostic importance of
      rituximab and radiotherapy in patients with primary mediastinal large B-cell
      lymphoma (PMBCL) receiving doxorubicin-containing chemotherapy. Seventy-nine
      patients with PMBCL received CHOP chemotherapy with (n = 39) or without rituximab
      (n = 40), and 60 patients received additional radiotherapy. Patients treated with
      rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) had
      significantly superior survival rates. The 5-year overall survival (OS) and
      progression-free survival (PFS) rates were 83.7% and 76.7% for R-CHOP, compared
      with 48.3% (p = 0.011) and 44.2% (p = 0.012) for CHOP, respectively. Similarly,
      the 5-year OS and PFS rates for early stage patients were 93.8% and 84.6% with R
      CHOP, and 52.0% (p = 0.002) and 46.6% (p = 0.003) with CHOP, respectively.
      Patients treated with chemotherapy and radiotherapy had better survival and local
      control (LC) rates compared with chemotherapy alone. The 5-year OS, PFS and LC
      rates for early stage patients were 73.6%, 69.9% and 92.6% for chemotherapy and
      radiotherapy, and 50.8% (p = 0.076), 36.9% (p = 0.008) and 56.4% (p < 0.001) for
      chemotherapy alone, respectively. Early stage patients treated with R-CHOP and
      radiotherapy had 5-year OS, PFS and LC rates of 96.4%, 85.9% and 93.1%. R-CHOP
      plus consolidation radiotherapy was associated with excellent survival and LC
      rates. 

PMID- 23137071
TI  - The association of depression with pain-related treatment utilization in patients
      with multiple sclerosis.
AB  - OBJECTIVE: To better understand the association of depression with pain treatment
      utilization in a multiple sclerosis (MS) population. DESIGN: Cross-sectional
      survey. SETTING: Community-based survey. PARTICIPANTS: Convenience sample of 117
      individuals with MS. MAIN OUTCOME MEASURES: Participants provided demographic
      information, descriptive information on utilization of pain treatments, pain
      intensity ratings on a 0-10 numerical rating scale, and depressive symptoms on
      the Patient Health Questionnaire-9 (PHQ-9). RESULTS: Participants reporting
      clinical levels of depressive symptoms (PHQ-9 >=10) reported that they tried more
      pain treatments previously relative to participants with PHQ-9 <10; however, the
      two groups did not differ in the number of treatments they were currently using.
      Additionally, participants with PHQ-9 >=10 had more visits to providers for pain
      treatment relative to the group with PHQ-9 <10. In subsequent analyses, results
      showed that these differences were no longer significant after controlling for
      level of pain intensity. CONCLUSIONS: The results demonstrate that depression is
      not associated with higher pain treatment utilization. These findings support the
      assertion in previous studies that the mechanism by which depression impacts
      medical utilization is through increased appointments for nonspecific complaints,
      not for specific medical problems. While this suggests that treating depression
      may not be helpful in reducing pain treatment utilization specifically, it
      remains important to treat depression to reduce pain-related suffering and
      medical utilization more broadly.

PMID- 23137072
TI  - Transannular O-heterocyclization: a useful tool for the total synthesis of
      Murisolin and 16,19-cis-Murisolin.
AB  - Transannular O-heterocyclization is applied as a key step in a total synthesis.
      This highly stereoselective and metal-free transformation introduces four
      stereocenters in one step. It was chosen to be the pivotal step in the synthesis
      of Murisolin and 16,19-cis-Murisolin, two annonaceous acetogenins. The efficiency
      of this synthesis is further illustrated by a stereodivergent late-stage
      separation of both synthetic routes.

PMID- 23137073
TI  - Familial Mediterranean fever in Germany: clinical presentation and amyloidosis
      risk.
AB  - OBJECTIVE: To characterize patients with familial Mediterranean fever (FMF) with
      and without AA amyloidosis living in Germany. METHOD: Clinical and genetic data
      from 64 FMF patients were analysed for amyloidosis risk factors. RESULTS: Fifty
      five patients (85%) were of Turkish or Armenian origin. Thirty-one patients (48%)
      developed FMF symptoms before the age of 16 years. Sixteen patients (26%) became
      symptomatic after age 20. Symptoms reported were peritonitis (95%), fever (78%),
      pleuritis (59%), arthralgia (60%), arthritis (32%), erysipelas-like erythema
      (23%), and vasculitis (8%). FMF diagnosis was delayed for a median of 8.0 years.
      Genetic analysis confirmed M694V as the most prevalent Mediterranean fever (MEFV)
      gene mutation in 46 out of 59 patients (78%). M694V homozygosity was associated
      with an earlier FMF onset (median age 5.5 years, p = 0.0001) and a higher
      prevalence of peritonitis (p = 0.007) and pleuritis (p = 0.0007) compared to
      patients without an M694V mutation. AA amyloidosis was detected in 16 patients
      (25%) at a median age of 36.5 years and tended to be associated with a higher age
      at disease onset (p = 0.062) and a higher FMF activity score (p = 0.093). AA
      amyloidosis was significantly associated with a higher age at FMF diagnosis (p =
      0.0022). CONCLUSIONS: Clinical symptoms of FMF-affected migrants living in
      Germany resemble those observed in their home country. In particular, patients
      with an onset of FMF symptoms after age 20 and a later FMF diagnosis have a high
      risk of AA amyloidosis. Symptomatic patients who originate from countries with a
      higher FMF prevalence should be screened for FMF and proteinuria.

PMID- 23137074
TI  - Parents' actions, challenges, and needs while enabling participation of children
      with a physical disability: a scoping review.
AB  - BACKGROUND: Pediatric rehabilitation considers Family-centered service (FCS) as a
      way to increase participation of children with a physical disability in daily
      life. An important principal is that parents greatly contribute to their child's
      participation at school, at home, and in the community. However, it is unclear
      what kind of information is available from literature about what parents actually
      do to support their child's participation and what problems and needs they
      experience? Hence, the aim of this study was to provide an overview of the
      actions, challenges, and needs of parents in enabling participation of their
      child with a physical disability that is neurological and non-progressive in
      nature. METHODS: Scoping review with extensive literature search (September 2011)
      and a thematic analysis to synthesize findings. RESULTS: Fourteen relevant
      articles revealed two major themes: 'parents enable and support performance of
      meaningful activities' and 'parents enable, change and use the environment'. Each
      theme holds a number of actions (e.g. choosing the right type of meaningful
      activities for facilitating social contacts) and challenges (e.g. negative
      attitudes of other people). Less information is available about the needs of
      parents. CONCLUSIONS: This study indicates that parents apply a broad range of
      strategies to support participation of their children. They experience many
      challenges, especially as a result of constraints in the social and physical
      environments. However, this review also shows that little is known about needs of
      parents in facilitating participation. As Family-centered service (FCS)
      philosophy is all about the needs of the child and the family, it is essential to
      further investigate the needs of the parents and to understand if and to what
      extent they wish to be supported in enabling their child's participation in daily
      life.

PMID- 23137075
TI  - Clustering of deaths in families: infant and child mortality in historical
      perspective.
AB  - This introduction surveys the field of family clustering of deaths and discusses
      the contributions in this special issue. The main focus is on mortality in
      historical contexts. Clustering of deaths in families has been found both in
      historical and contemporary populations, and we argue that the 'family approach'
      to infant and child mortality yields important and interesting insights for our
      understanding of different mortality patterns and the mortality transition. The
      articles in this issue, representing different but complementary approaches to
      the problem of death clustering, demonstrate that we should be aware of the
      strong family effects on child health, but also that we need to develop adequate
      methods for the analysis of this complex phenomenon. Here we discuss several
      explanations for death clustering, such as different biodemographic factors and
      those focusing on socioeconomic and cultural variables. We also discuss some of
      the methodological challenges in studying family clustering, and emphasize the
      need for comparison and the adoption of common measures.

PMID- 23137076
TI  - Historical trends in the correlation of sibling deaths in infancy in the
      Netherlands.
AB  - In this article, we study temporal, regional, and social variation in infant and
      childhood death clustering in The Netherlands, using data from three provinces.
      The data relate to children born in 90,000 marriages contracted between the
      beginning and the last quarter of the nineteenth century. Descriptive indicators
      show that death clustering was more frequent in the province of Zeeland and more
      common in the lower classes, and that it increased in two provinces over time.
      Shared frailty hazard models make it clear that the number of children who died
      before the birth of an index child had a negative effect on the mortality of
      index children, whereas earlier stillbirths and the number of children who died
      when the index child was at a young age had an increasing effect on the mortality
      of index children.

PMID- 23137077
TI  - The effect of Rh-negative disease on perinatal mortality: some evidence from the
      Skelleftea region, Sweden, 1860-1900.
AB  - The Rh-negative gene is a well-known cause of perinatal mortality. In this
      article, we analyze the possible role of Rh disease in perinatal mortality and
      stillbirths in a particular historical setting: the Skelleftea region in northern
      Sweden between 1860 and 1900. The data used for the study cover 23,067 children
      born to 4,943 women. The exact impact is not possible to establish using
      historical data, but the typical pattern of the disease allows us to make
      estimations. The expected levels based on knowledge of blood group distribution,
      the risk of sensitization from Rh incompatability, and the risk of perinatal
      mortality in births by sensitized mothers are compared with the observed levels.
      The results show that Rh disease was important for perinatal mortality and
      clustering of deaths within families.

PMID- 23137078
TI  - Did factory girls make bad mothers? Women's labor market experience, motherhood,
      and children's mortality risks in the past.
AB  - Prior research has suggested that the quality of maternal care given to infants
      and small children plays an important role in the strong clustering of children's
      deaths. In this article, we investigate the quality of maternal care provided by
      those women who most nineteenth-century social commentators declared would never
      make good housewives or mothers: the young girls and women working in textile
      mills. We carried out this examination using an analysis of children's mortality
      risks in two textile cities in The Netherlands between roughly 1900 and 1930. Our
      analysis suggests that these children's clustered mortality risks cannot have
      resulted from either their mothers' labor market experience or biological or
      genetic factors.

PMID- 23137079
TI  - Are stepmothers evil or simply unskilled? Infant death clustering in recomposed
      families.
AB  - We measure the concentration of infant deaths in families in the historical
      populations of Krummhorn, Germany and Quebec, Canada in order to investigate
      whether mothers in recomposed families differ regarding their maternal quality.
      In particular, we are interested in whether stepmothers in Krummhorn are
      responsible for a diminution in the survival of their stepchildren because they
      poorly substitute maternal child care or because they disadvantage their
      stepchildren. The concentrations of infant deaths within the two populations are
      measured with Lorenz curves and Gini coefficients, and are compared with expected
      concentrations given by draws from a binomial distribution. Alleged differences
      between actual and calculated concentrations represent "causal" death clustering.
      In the Krummhorn region there is little evidence for "causal" death clustering
      that would indicate variations regarding their maternal quality, whereas Quebec
      mothers exhibit a distinctively higher concentration of infant deaths.

PMID- 23137080
TI  - Clustering of child mortality in a contemporary polygamous population in Africa.
AB  - Child mortality, defined here as mortality under age five, is not evenly
      distributed but found in clusters. In a contemporary polygamous population in
      Ghana with extended families, we separate clustering at the parental and
      household levels, which are often overlapping and inseparable in other historical
      studies. For eight years, we followed 28,994 individuals, including 9,288
      children under the age of five, in 1,703 households. We identified four
      determinants that had a significant effect on child mortality: sex of the child,
      age of the child, drinking source, and socioeconomic status. After correcting for
      these determinants, we still identified significant clustering of child mortality
      at the level of the village (covariance [cov] = 0.02, p = .04), household (cov =
      0.14, p = .003), father (cov = 0.24, p = .001), and mother (cov = 0.18, p = .05).
      The present data provide clues regarding the levels at which to look for
      unidentified determinants of child mortality and suggest that the importance of
      the father could be larger than previously thought.

PMID- 23137081
TI  - On statistical methods for clustering: a case study on infant mortality, Northern
      Sweden, 1831-1890.
AB  - This article considers the interfamily clustering of infant mortality (defined as
      mortality during the first year of life). We developed and evaluated statistical
      tools to detect clustering and a measure to quantify excess clustering for
      nineteenth-century data from Skelleftea, Sweden. The detection was performed
      using the standard methods of generalized linear models and logistic regression.
      The index of clustering was constructed by comparing the observed numbers of
      families with specific numbers of deaths to the corresponding observed numbers,
      after correcting for explanatory variables. To the best of our knowledge, no
      clustering index of this kind has ever been created.

PMID- 23137083
TI  - Alcohol consumption among drivers subject to the Swiss license restriction of
      zero tolerance when driving.
AB  - BACKGROUND: The restriction of zero tolerance when driving (ZTD) imposed on
      drivers in Switzerland means that they may drink no alcohol at all before driving
      and basically consume only moderate amounts of alcohol at any other time. The
      Institute of Traffic Medicine in Zurich has recently started to confirm this
      moderate alcohol consumption by analyzing hair samples for ethyl glucuronide
      (EtG), a metabolite of ethanol. On the basis of the EtG results, this article
      looks at the alcohol consumption of drivers subject to ZTD restrictions and
      determines what recommendations can be made in relation to traffic safety. In
      particular, the behavior of people with alcohol dependence, who are known to have
      a reduced ability to control their drinking, is looked at in detail. METHODS:
      Data from all 250 persons with ZTD restrictions, assessed at our Institute in
      2010, were evaluated retrospectively. These drivers included 220 men and 30
      women, all aged between 21 and 75 (mean age 41 +/- 12 years). At the time of the
      expert review, 26 (10.4%) had no record of driving under the influence (DUI), 121
      (48.4%) had one DUI offense, and the rest had 2 or more drunk driving offenses.
      The length of time for which ZTD is imposed is determined on an individual basis,
      depending on the history of use and course of events. RESULTS: EtG hair analysis
      of all 250 drivers with ZTD restrictions provided the following results: EtG
      assay was not performed in 16 cases (6%); 126 drivers (50%) did not have any
      detectable EtG (corresponding to total abstinence); 93 (37%) had an EtG
      concentration within the limits of social drinking; and the EtG concentration
      indicated excessive alcohol use by 15 people (6%). EtG was found to be in the
      range of excessive alcohol consumption in 3 (8%) of the drivers diagnosed as
      alcohol dependent. It was seen that the majority of those drivers who had
      previously abstained totally from alcohol continued to do so. None of the drivers
      with ZTD restrictions committed any drunk driving offenses in 2010. CONCLUSIONS:
      Imposing a ZTD restriction on individuals with moderate alcohol consumption or
      those with previous alcohol problems who have been stable for some time and now
      drink little or no alcohol is worthwhile. In addition, total abstinence from
      alcohol should be made a license restriction for those with serious alcohol
      dependence, due to the poor long-term prognosis.

PMID- 23137084
TI  - Alcohol, drugs, and road traffic crashes in India: a systematic review.
AB  - OBJECTIVE: India reported the highest number of road traffic crashes, related
      injuries, and deaths among all countries in the world, with 105,725 road traffic
      fatalities and 452,922 nonfatal road traffic injuries in 2007. In this report we
      present a systematic review of available literature on the use of psychoactive
      substances (alcohol and drugs) among road users, particularly those involved in
      road traffic crashes (RTCs). METHODS: MEDLINE, EMBASE, Ind Medica, and several
      other databases were searched for reports published between 1980 and 2011 that
      present data on the prevalence or extent of substance use among road users in
      India. RESULTS: Among the 23 studies eligible for the review, alcohol was
      reported by all, but only 2 mentioned the use of drugs. Most of the studies were
      hospital based, included injured or killed road users, and belonged to southern
      parts of India. Seven studies did not report any method for detecting alcohol
      use, whereas 7 used analytical testing, 7 used self-reporting, and 2 used
      observation. Utilizing the various means of verification, the studies reported
      that 2 to 33 percent of injured and 6 to 48 percent of killed RTC victims had
      consumed alcohol or drugs; only 2 mentioned drugs without specifying which types.
      Most studies did not distinguish between drivers, passengers, bicyclists, and
      pedestrians, and none investigated alcohol or drug use among those responsible
      for the accident. CONCLUSION: A significant proportion of injured or killed road
      users in India had used alcohol before the accident. However, the existing
      studies cannot be used to estimate the risk of accident involvement among drunk
      drivers. There is a need for more rigorous research and capacity building on
      substance use vis-a-vis road traffic crashes.

PMID- 23137085
TI  - In search of a standard for assessing the crash risk of driving under the
      influence of drugs other than alcohol; results of a questionnaire survey among
      researchers.
AB  - OBJECTIVE: To find a gold standard for crash risk assessment studies in the field
      of driving under the influence of psychoactive substances. METHODS: A
      questionnaire survey on methodological aspects concerning study designs was sent
      to researchers in the field of driving under the influence of psychoactive
      substances. The questionnaire was aimed at the 4 main study designs to assess the
      crash risk of driving under the influence: case-control studies, culpability
      studies, pharmaco-epidemiological studies, and experimental studies. RESULTS: The
      response rate for the questionnaire was 68 percent (N = 57). Forty-six percent of
      the respondents had a preference for assessing the crash risk by means of case
      control studies, 35 percent by means of experimental studies, 14 percent by means
      of culpability studies, and 5 percent by means of pharmaco-epidemiological
      studies. In practice, however, only 51 percent of the researchers actually used
      the study type they preferred in theory. For the 4 most commonly used study
      designs, similarity rates varied from 66 to 81 percent for the theoretically
      preferred design and from 52 to 77 percent for the design that was actually
      applied. CONCLUSIONS: Based on the results of the questionnaire survey, it can be
      concluded that despite several attempts in the past to standardize study design,
      there is still no common standard for assessing the crash risk of driving under
      the influence. The differences are not only caused by practical, legal,
      financial, or ethical issues but also by differences between researchers
      concerning their theoretically preferred study design.

PMID- 23137086
TI  - A comparison of the effect of mobile phone use and alcohol consumption on driving
      simulation performance.
AB  - OBJECTIVE: The present study compared the effects of a variety of mobile phone
      usage conditions to different levels of alcohol intoxication on simulated driving
      performance and psychomotor vigilance. METHODS: Twelve healthy volunteers
      participated in a crossover design in which each participant completed a
      simulated driving task on 2 days, separated by a 1-week washout period. On the
      mobile phone day, participants performed the simulated driving task under each of
      4 conditions: no phone usage, a hands-free naturalistic conversation, a hands
      free cognitively demanding conversation, and texting. On the alcohol day,
      participants performed the simulated driving task at four different blood alcohol
      concentration (BAC) levels: 0.00, 0.04, 0.07, and 0.10. Driving performance was
      assessed by variables including time within target speed range, time spent
      speeding, braking reaction time, speed deviation, and lateral lane position
      deviation. RESULTS: In the BAC 0.07 and 0.10 alcohol conditions, participants
      spent less time in the target speed range and more time speeding and took longer
      to brake in the BAC 0.04, 0.07, and 0.10 than in the BAC 0.00 condition. In the
      mobile phone condition, participants took longer to brake in the natural hands
      free conversation, cognitively demanding hands-free conversation and texting
      conditions and spent less time in the target speed range and more time speeding
      in the cognitively demanding, hands-free conversation, and texting conditions.
      When comparing the 2 conditions, the naturalistic conversation was comparable to
      the legally permissible BAC level (0.04), and the cognitively demanding and
      texting conversations were similar to the BAC 0.07 to 0.10 results. CONCLUSION:
      The findings of the current laboratory study suggest that very simple
      conversations on a mobile phone may not represent a significant driving risk
      (compared to legally permissible BAC levels), whereas cognitively demanding,
      hands-free conversation, and particularly texting represent significant risks to
      driving.

PMID- 23137087
TI  - A note: the changing gender demographics of U.S. drivers.
AB  - OBJECTIVE: This study examined recent trends in gender differences in the
      percentage of persons with driver's licenses as a function of age by comparing
      data from 2010 and 1995. METHOD: The analysis used data from the Federal Highway
      Administration and the U.S. Census Bureau. RESULTS: There are 2 main findings.
      First, the percentage of males with a driver's license decreased from 1995 to
      2010 for those younger than 60; for females a decrease occurred for those younger
      than 50. Second, in 2010, proportionally more males younger than 45 had a
      driver's license than was the case for females; the opposite relationship held
      for persons 45 and older. CONCLUSIONS: The observed gender trends in driver
      licensing will likely have major implications on the extent and nature of vehicle
      demand, energy consumption, and road safety.

PMID- 23137088
TI  - Driving decisions when leaving electronic music dance events: driver, passenger,
      and group effects.
AB  - OBJECTIVES: The goal of this article was to identify characteristics of drivers
      and passengers that predicted peer groups whose drivers exit dance clubs with
      alcohol levels indicative of impairment (blood alcohol content [BAC] >= 0.05
      g/dL). METHODS: We used the portal survey methodology to randomly sample groups
      of electronic music dance event (EMDE) patrons as they entered and exited a club.
      From May through November 2010, data were collected from 38 EMDEs hosted by 8
      clubs in the San Francisco Bay area. Data included in these analyses are results
      from breath samples for measuring BAC and self-report data on demographics,
      recent drinking history drinking, drinking intentions, travel to and from the
      clubs, and the familiarity/experience with other group members. These data were
      collected from a subset of 175 drivers and 272 passengers. RESULTS: Although
      drivers drank less than passengers, one driver in 5 groups had a BAC indicative
      of elevated crash risk (BAC >= 0.05 g/dL). Groups of drivers and/or passengers
      with a recent history of binge drinking were more likely to have drivers with
      BACs >= 0.05 g/dL. One unanticipated finding was that drivers who knew more group
      members relatively well were more likely to exit the club with a BAC >= 0.05
      g/dL. Additionally, we found that groups with all female passengers were at
      greater risk for having a driver whose BAC was >= 0.05 g/dL. CONCLUSIONS: Some
      group characteristics predicted drivers who exit clubs with BACs >= 0.05 g/dL.
      One intervention strategy to promote safety might be to encourage group members
      to reconsider who is sober enough to drive away from the club; for some groups, a
      change of drivers would be a safer choice, because a passenger may have a
      relatively safe BAC. Groups of females appear to have a particularly elevated
      risk of having a driver whose BAC exceeds 0.05 g/dL, and new intervention efforts
      should be particularly directed to these at-risk groups.

PMID- 23137089
TI  - Is passenger vehicle incompatibility still a problem?
AB  - OBJECTIVE: Passenger cars often are at a disadvantage when colliding with light
      trucks (sport utility vehicles [SUVs] and pickups) due to differences in mass,
      vehicle structural alignment, and stiffness. In 2003, vehicle manufacturers
      agreed to voluntary measures to improve compatibility, especially in front-to
      front and front-to-side crashes, with full adherence to be achieved by September
      2009. This study examined whether fatality rates are consistent with the expected
      benefit of this agreement. METHODS: Analyses examined 2 death rates for 1- to 4
      year-old passenger vehicles during 2000-2001 and 2008-2009 in the United States:
      occupant deaths per million registered vehicle years in these vehicles and deaths
      in other cars that collided with these vehicles in 2-vehicle crashes per million
      registered vehicle years. These rates were computed for each study period and for
      cars/minivans (referred to as cars), SUVs, and pickups by curb weight (in 500
      pound increments). The latter death rate, referred to as the car crash partner
      death rate, also was computed for front-to-front crashes and front-to-side
      crashes where the front of the 1- to 4-year-old vehicle struck the side of the
      partner car. RESULTS: In both study periods, occupant death rates generally
      decreased for each vehicle type both with increasing curb weight and over time.
      SUVs experienced the greatest declines compared with cars and pickups. This is
      due in part to the early fitment of electronic stability control in SUVs, which
      drastically reduced the incidence of single-vehicle rollover crashes. Pickups had
      the highest death rates in both study periods. Car crash partner death rates
      generally declined over time for all vehicle categories but more steeply for SUVs
      and pickups colliding with cars than for cars colliding with cars. In fact, the
      car crash partner death rates for SUVs and cars were nearly identical during 2008
      2009, suggesting that the voluntary design changes for compatibility have been
      effective. Car crash partner death rates also declined for pickups, but their
      rates were consistently the highest in both study periods. CONCLUSION: It is
      impossible to disentangle the individual contributions of the compatibility
      agreement, improved crashworthiness of cars, and other factors in reducing car
      crash partner fatality rates. However, the generally larger reductions in car
      crash partner death rates for SUVs and pickups indicate the likely benefits of
      the agreement. Overall, this study finds that the system of regulatory testing,
      voluntary industry initiatives, and consumer information testing has led to a
      passenger vehicle fleet that is much more compatible in crashes.

PMID- 23137090
TI  - Potential benefits of underride guards in large truck side crashes.
AB  - OBJECTIVE: To evaluate the maximum potential for side underride guards (SUGs) to
      reduce passenger vehicle occupant fatalities and injuries in crashes with large
      trucks in the United States. METHODS: Examination of the Large Truck Crash
      Causation Study (LTCCS) identified 206 crash events involving a passenger vehicle
      impact with the side of a large truck. Each case was evaluated to determine
      whether the most severe injury sustained by a passenger vehicle occupant was a
      result of the impact with the side of the truck and whether an SUG could have
      reduced the injury severity. Data from the 2006-2008 Fatality Analysis Reporting
      System (FARS) and Trucks Involved in Fatal Accidents (TIFA) survey were used to
      compare the types of trucks involved in all fatal side impacts with passenger
      vehicles with the truck types in the LTCCS cases that were studied. FARS and TIFA
      data also were used to estimate the total annual number of passenger vehicle
      occupants killed in truck side impacts. RESULTS: In 143 of the 206 cases, the
      truck side impact produced the most severe injury sustained by a passenger
      vehicle occupant. In the other cases, no passenger vehicle occupant was injured
      or the most severe injury was due to an event preceding or following the truck
      side impact. Forty-nine of these occupants sustained injuries coded as level 3 or
      higher on the abbreviated injury scale (AIS) or were killed. SUGs could have
      reduced injury severity in 76 of the 143 cases, including 38 of the 49 cases with
      an AIS >= 3 coded injury or fatality. Semi-trailers were the most common type of
      impacted truck unit, both overall and when considering only cases where an SUG
      could have mitigated injury severity. Crashes where the front of the passenger
      vehicle struck the side of the semi-trailer perpendicularly or obliquely from the
      oncoming direction were less common overall than side-to-side and oblique/same
      direction crashes but more often produced an AIS >= 3 injury or fatality. The
      distribution of truck types in the LTCCS sample was similar to that in the FARS
      and TIFA data. Overall, around 1600 passenger vehicle occupants were killed in 2
      vehicle truck side impact crashes during 2006-2008, or 22 percent of all
      passenger vehicle occupants who died in 2-vehicle crashes with large trucks.
      CONCLUSIONS: Structural incompatibility was a common factor in LTCCS crashes
      between passenger vehicles and the sides of large trucks. SUGs could have reduced
      injury risk in around three fourths of the crashes that produced an AIS >= 3
      injury or fatality. Most of these crashes involved semi-trailers. However, the
      necessary strength and location of these SUGs present technical challenges that
      need to be addressed.

PMID- 23137091
TI  - Evaluation of the head kinematics of the Q3 model and a modified Q3 model by
      means of crash reconstruction.
AB  - OBJECTIVE: One objective of this study is to evaluate the head kinematics of the
      Q3 model. Another objective is to evaluate the effect on head kinematics of
      increased thoracic spine flexibility; more humanlike mass distribution; and more
      humanlike body geometry in the Q3 model. The evaluations were based on the head
      kinematics of children deduced from real crashes and on new data of mass
      distribution and updated body dimensions for 3-year-olds. METHODS: The head
      kinematics of the Q3 model was evaluated by comparing the Q3 model's head
      displacement response with the deduced response of 3-year-old children in real
      crashes. To do so, data from crashes were collected. The data were used to
      develop the mathematical vehicle and restraint system models (MADYMO, TASS, the
      Netherlands). Three crashes involving 3-year-old children in frontal impacts were
      reconstructed. The models were run 35 times each (one model per crash), each time
      with a different setting to each of the variables for which the exact value was
      not known. Examples of those variables include crash pulse, initial dummy
      position, and initial seat belt position. Two versions of the Q3 model were used:
      one that correlated with the Q3 ATD and one that was modified regarding
      anthropometry and thoracic flexibility. The basis for the updated anthropometry
      was new data regarding characteristic dimensions and mass distribution collected
      at a Swedish hospital. RESULTS: In the anthropometry study, 26 children were
      measured. The main differences between the average of the measured children and
      the Q3 model were found in the mass distribution of the torso and thighs: the
      Q3's pelvis was too heavy and the thorax, abdomen/lumbar spine, and thighs were
      too light. Another difference was identified in the buttock-knee length. Two of
      the 3 reconstructed crashes had confirmed head impacts. The Q3 model responded
      with head kinematics that reflected the deduced courses of events for the real
      children in one of 3 crashes (the one without head impact). The modified Q3 model
      reflected the real children in 2 of 3 crashes. CONCLUSIONS: In high-severity,
      straight frontal crashes, the Q3 model predicted non-head impact adequately.
      However, in oblique frontal crashes, the Q3 model did not sufficiently predict
      the head impacts. The modified Q3 model predicted the head impacts better than
      the Q3 model did. Greater flexibility of the thorax and redistributed mass made a
      positive difference regarding the head kinematics.

PMID- 23137092
TI  - An assessment of commercial motor vehicle driver distraction using naturalistic
      driving data.
AB  - OBJECTIVE: This study analyzed naturalistic driving data from commercial trucks
      (3-axle and tractor-trailer/tanker) and buses (transit and motorcoach) during a 3
      month period. METHODS: The data set contained 183 commercial truck and bus fleets
      comprising 13,306 vehicles and included 1085 crashes, 8375 near crashes, 30,661
      crash-relevant conflicts, and 211,171 baseline events. Study results documented
      the prevalence of tertiary tasks and the risks associated with performing these
      tasks while driving. RESULTS: Results indicated the odds of involvement in a
      safety-critical event differed as a function of performing different cell phone
      related subtasks while driving. Although the odds ratio for talking/listening on
      a cell phone while driving was found to not significantly increase the likelihood
      of involvement in a safety-critical event, other cell phone subtasks (e.g.,
      texting, dialing, reaching) were found to significantly increase the odds of
      involvement in a safety-critical event. CONCLUSIONS: The results suggest that
      cell phone use while driving should not be considered a simple dichotomous task
      (yes/no). Consideration should instead be made for a set of discrete cell phone
      subtasks that are each associated with varying levels of risk. Several hypotheses
      are presented to explain why cell phone use while driving was found to not
      increase the likelihood of involvement in a safety-critical event.

PMID- 23137093
TI  - Childhood road safety behaviors in China: a cross-sectional study of Guangzhou
      city.
AB  - OBJECTIVE: This article examines traffic safety behaviors for different types of
      road users among children aged 0 to 17 years in Guangzhou, China. METHODS: A
      stratified cluster sample of 7034 children from pediatric clinics (816 children
      aged 0-2 years who are receiving vaccines), kindergartens (1148 children aged 3-5
      years), primary schools (2410 children aged 6-11 years), and secondary schools
      (2660 children aged 12-17 years) was collected by self-reported questionnaire
      surveys. The respondents were instructed to respond to each behavior question,
      using response choices scoring from 0 to 3. An 18-item-weighted Road Safety
      Behavior Index (RSBI), including 5 items for walking, 7 items for cycling, 2
      items for public transport, and 4 items for private motor vehicles, was developed
      to quantify the child road safety behaviors and further investigate their
      interrelations with the sociodemographic factors among different age groups and
      travel categories. A higher RSBI indicates a lower risk of childhood road safety.
      RESULTS: Results from statistical analysis indicate that (1) the effects of
      children's sociodemographic characteristics on the RSBIs differ greatly
      concerning each particular travel category; and (2) RSBIs are associated more
      with child-related characteristics than with parent-related characteristics as
      the age of the children's group increases. The research findings from analyzing
      the self-report questionnaires were further validated with field observational
      records, medical records, and police records. CONCLUSIONS: The article concludes
      with some recommendations for preventing the increasing toll of road traffic
      injury among Chinese children, which include (1) continuing educational efforts
      to increase knowledge of road safety and reduce traffic risk behaviors for
      children and their parents; (2) creating a safe and convenient environment for
      walking, cycling, and public transport travelers; and (3) promoting legislation
      and enforcement such as the mandatory usage of bicycle helmets and child
      passenger restraints.

PMID- 23137094
TI  - Effects of booster seat laws on injury risk among children in crashes.
AB  - OBJECTIVE: Belt-positioning booster seats have been shown to reduce injury risk
      among child passengers aged 4 to 8 in motor vehicle crashes. To encourage the use
      of booster seats, many states have enacted laws that require the use of either a
      child restraint with internal harness or a belt-positioning booster seat, but the
      specific age range covered by the laws varies by state. Previous studies have
      found evidence that booster seat laws are effective in reducing injury risk among
      children, but these studies primarily have included states with younger age
      requirements (e.g., ages 4-6) for booster seats. The objective of the present
      study was to examine the effectiveness of booster seat laws in several states
      that cover children through age 7 or 8. METHODS: Police-reported crash data from
      5 states--Missouri, North Carolina, Pennsylvania, Wisconsin, and Wyoming--were
      used to compare population-based injury rates, restraint use, and seating
      position among children before and after booster seat laws. The pre-law period
      was comprised of the 2 calendar years prior to the year of enactment of the
      booster seat law, and the post-law period was comprised of the 2 calendar years
      after the year of the effective start of the booster seat law. Effectiveness
      estimates were adjusted using a comparison group of children aged 9 to 12 in the
      same states who were not covered by the booster seat laws. RESULTS: Among
      children in crashes who were affected by law changes in the 5 study states, the
      per capita rate of children using child safety seats (either a harnessed child
      restraint or booster seat) increased nearly 3 times, and the per capita rate of
      children riding in rear seats increased 6 percent after the booster seat laws
      were implemented. Booster seat laws were associated with a 5 percent reduction in
      the per capita rate of children who sustained injuries of any severity and a 17
      percent reduction in the per capita rate of children who sustained fatal or
      incapacitating injuries. CONCLUSIONS: Results provide evidence that booster seat
      laws are effective in increasing the use of child safety seats, increasing the
      placement of children in rear seats, and reducing injuries, especially severe
      injuries, among children covered by the laws.

PMID- 23137095
TI  - Repositioning the knee joint in human body FE models using a graphics-based
      technique.
AB  - OBJECTIVE: Human body finite element models (FE-HBMs) are available in standard
      occupant or pedestrian postures. There is a need to have FE-HBMs in the same
      posture as a crash victim or to be configured in varying postures. Developing FE
      models for all possible positions is not practically viable. The current work
      aims at obtaining a posture-specific human lower extremity model by reconfiguring
      an existing one. METHODOLOGY: A graphics-based technique was developed to
      reposition the lower extremity of an FE-HBM by specifying the flexion-extension
      angle. Elements of the model were segregated into rigid (bones) and deformable
      components (soft tissues). The bones were rotated about the flexion-extension
      axis followed by rotation about the longitudinal axis to capture the twisting of
      the tibia. The desired knee joint movement was thus achieved. Geometric
      heuristics were then used to reposition the skin. A mapping defined over the
      space between bones and the skin was used to regenerate the soft tissues. Mesh
      smoothing was then done to augment mesh quality. RESULTS: The developed method
      permits control over the kinematics of the joint and maintains the initial mesh
      quality of the model. For some critical areas (in the joint vicinity) where
      element distortion is large, mesh smoothing is done to improve mesh quality.
      CONCLUSIONS: A method to reposition the knee joint of a human body FE model was
      developed. Repositions of a model from 9 degrees of flexion to 90 degrees of
      flexion in just a few seconds without subjective interventions was demonstrated.
      Because the mesh quality of the repositioned model was maintained to a predefined
      level (typically to the level of a well-made model in the initial configuration),
      the model was suitable for subsequent simulations.

PMID- 23137098
TI  - The small RNA-based odyssey of epigenetic information in plants: from cells to
      species.
AB  - In the past years a plethora of roles for small RNAs (sRNAs) have been revealed
      in developmental biology, physiology, pathogen interactions, and more recently in
      genome stability and transposon control. sRNAs have a repressive impact on gene
      expression by directly interfering with endogenous mRNAs or virus RNA, or by
      maintaining heterochromatin. In plants, the most abundant sRNAs are by far the
      ones produced from heterochromatic loci and playing a role in epigenetic
      regulation. Here, I review some specific examples of the roles of these sRNAs
      belonging to the class of small interfering RNAs (siRNAs) in controlling the
      epigenetic regulation of the genome. I will highlight their role as mediators of
      epigenetic information at various organization levels: between two alleles within
      a single cell, two tissues within an organism, two individuals or two generations
      within a species, and even two species within a kingdom.

PMID- 23137097
TI  - Identification of sulfated metabolites of 4-chlorobiphenyl (PCB3) in the serum
      and urine of male rats.
AB  - Polychlorinated biphenyls (PCBs) are legacy pollutants that exert toxicities
      through various mechanisms. In recent years exposure to PCBs via inhalation has
      been recognized as a hazard. Those PCBs with lower numbers of chlorine atoms (LC
      PCBs) are semivolatile and have been reported in urban air, as well as in the
      indoor air of older buildings. LC-PCBs are bioactivated to phenols and further to
      quinone electrophiles with genotoxic/carcinogenic potential. We hypothesized that
      phenolic LC-PCBs are subject to conjugation and excretion in the urine. PCB3,
      often present in high concentrations in air, is a prototypical congener for the
      study of the metabolism and toxicity of LC-PCBs. Our objective was to identify
      metabolites of PCB3 in urine that could be potentially employed in the estimation
      of exposure to LC-PCBs. Male Sprague-Dawley rats (150-175 g) were housed in
      metabolism cages and received a single intraperitoneal injection of 600 MUmol/kg
      body weight of PCB3. Urine was collected every 4 h; rats were euthanized at 36 h;
      and serum was collected. LC/MS analysis of urine before and after incubation with
      beta-glucuronidase and sulfatase showed that sulfate conjugates were in higher
      concentrations than glucuronide conjugates and free phenolic forms. At least two
      major metabolites and two minor metabolites were identified in urine that could
      be attributed to mercapturic acid metabolites of PCB3. Quantitation by authentic
      standards confirmed that approximately 3% of the dose was excreted in the urine
      as sulfates over 36 h, with peak excretion occurring at 10-20 h after exposure.
      The major metabolites were 4'PCB3sulfate, 3'PCB3 sulfate, 2'PCB3 sulfate, and
      presumably a catechol sulfate. The serum concentration of 4'PCB3 sulfate was 6.18
      +/- 2.16 MUg/mL. This is the first report that sulfated metabolites of PCBs are
      formed in vivo. These findings suggest a prospective approach for exposure
      assessment of LC-PCBs by analysis of phase II metabolites in urine.

PMID- 23137099
TI  - Delayed villous maturation of the placenta: quantitative assessment in different
      cohorts.
AB  - Placental villous maturation is maximal in the 3rd trimester, with an abundance
      of terminal villi. Delayed villous maturation (DVM) of the placenta is associated
      with chromosomal abnormalities, gestational diabetes, and an adverse outcome.
      This study compares quantitative assessment of vasculo-syncytial membranes (VSM)
      in cases of liveborn infants, perinatal deaths, and controls. Cases were selected
      as follows: (1) liveborn infants with a qualitative diagnosis of DVM (n  =  15);
      (2) controls matched for gestational age whose placentas did not have DVM (n  = 
      15); (3) stillbirths (SB)/neonatal deaths (NND) showing DVM (n  =  13); and (4)
      SB from autopsies in which DVM was felt to be the cause of death (COD) (n  = 
      12). Vasculo-syncytial membranes were counted in 10 terminal villi in each of 10
      consecutive high-power fields on 3 slides. Data analysis was carried out using
      SPSS. Liveborn cases with DVM showed statistically significantly less VSM than
      controls (mean 1.01 vs 2.42, P < 0.0001). The SB/NND group also showed
      significantly less VSM than the control group (mean 0.46 vs 2.42, P < 0.0001) and
      less than the liveborn DVM group (mean 0.46 vs 1.01, P  =  0.001). The COD group
      was significantly different from the control group (mean 0.42 vs 2.42, P <
      0.0001) and the liveborn DVM group (mean 0.42 vs 1.01, P < 0.0001) but not
      significantly different from the SB/NND group. There is a quantitative reduction
      in VSM in cases of DVM compared to controls.

PMID- 23137100
TI  - Alpha chymotrypsin coated clusters of Fe3O4 nanoparticles for biocatalysis in low
      water media.
AB  - BACKGROUND: Enzymes in low water containing non aqueous media are useful for
      organic synthesis. For example, hydrolases in such media can be used for
      synthetic purposes. Initial work in this area was carried out with lyophilized
      powders of enzymes. These were found to have poor activity. Drying (removing bulk
      water) by precipitation turned out to be a better approach. As enzymes in such
      media are heterogeneous catalysts, spreading these precipitates over a large
      surface gave even better results. In this context, nanoparticles with their
      better surface to volume ratio provide obvious advantage. Magnetic nanoparticles
      have an added advantage of easy separation after the reaction. Keeping this in
      view, alpha chymotrypsin solution in water was precipitated over a stirred
      population of Fe3O4 nanoparticles in n-propanol. This led to alpha chymotrypsin
      activity coated over clusters of Fe3O4 nanoparticles. These preparations were
      found to have quite high transesterification activity in low water containing n
      octane. RESULTS: Precipitation of alpha chymotrypsin over a stirred suspension of
      Fe3O4 nanoparticles (3.6 nm diameter) led to the formation of enzyme coated
      clusters of nanoparticles (ECCNs). These clusters were also magnetic and their
      hydrodynamic diameter ranged from 1.2- 2.6 microns (as measured by dynamic light
      scattering). Transmission electron microscopy (TEM), showed that these clusters
      had highly irregular shapes. Transesterification assay of various clusters in
      anhydrous n-octane led to optimization of concentration of nanoparticles in
      suspension during precipitation. Optimized design of enzyme coated magnetic
      clusters of nanoparticles (ECCN 3) showed the highest initial rate of 465 nmol
      min-1 mg-1protein which was about 9 times higher as compared to the simple
      precipitates with an initial rate of 52 nmol min-1 mg-1 protein.Circular
      Dichroism (CD)(with a spinning cell accessory) showed that secondary structure
      content of the alpha Chymotrypsin in ECCN 3 [15% alpha-helix, 37% beta-sheet and
      48% random coil] was identical to the simple precipitates of alpha chymotrypsin.
      CONCLUSION: A strategy for obtaining a high activity preparation of alpha
      chymotrypsin for application in low water media is described. Such high activity
      biocatalysts are useful in organic synthesis.

PMID- 23137101
TI  - Protein expression studies of desmoplakin mutations in cardiomyopathy patients
      reveal different molecular disease mechanisms.
AB  - Mutations in the gene for desmoplakin (DSP) may cause arrhythmogenic right
      ventricular cardiomyopathy (ARVC) and Carvajal syndrome (CS). Desmoplakin is part
      of all desmosomes, which are abundantly expressed in both myocardial and
      epidermal tissue and serve as intercellular mechanical junctions. This study
      aimed to investigate protein expression in myocardial and epidermal tissue of
      ARVC and CS patients carrying DSP mutations in order to elucidate potential
      molecular disease mechanisms. Genetic investigations identified three ARVC
      patients carrying different heterozygous DSP mutations in addition to a
      homozygous DSP mutation in a CS patient. The protein expression of DSP in
      mutation carriers was evaluated in biopsies from myocardial and epidermal tissue
      by immunohistochemistry. Keratinocyte cultures were established from skin
      biopsies of mutation carriers and characterized by reverse transcriptase
      polymerase chain reaction, western blotting, and protein mass spectrometry. The
      results showed that the mutation carriers had abnormal DSP expression in both
      myocardial and epidermal tissue. The investigations revealed that the disease
      mechanisms varied accordingly to the specific types of DSP mutation identified
      and included haploinsufficiency, dominant-negative effects, or a combination
      hereof. Furthermore, the results suggest that the keratinocytes cultured from
      patients are a valuable and easily accessible resource to elucidate the effects
      of desmosomal gene mutations in humans.

PMID- 23137102
TI  - Kidney cancer in Sweden: a decrease in incidence and tumour stage, 1979 - 2001.
AB  - OBJECTIVE: In the Western world the incidence of renal cell carcinoma (RCC) has
      been increasing for several decades. In Sweden the incidence has decreased since
      1980. This may reflect better health of the population. Another possible
      explanation could be a decrease in incidentally diagnosed RCC. Since these
      tumours are smaller, relatively more advanced tumours would then enter the cancer
      registry. The aim of this study was to compare methods of detection of RCC,
      tumour characteristics and survival from three periods over a timespan of more
      than 20 years. MATERIAL AND METHODS: Adult patients (n = 515) with RCC were
      identified in a well-defined population-based area with the same incidence of RCC
      as the rest of Sweden. Patient data from three periods, 1979 - 1981 (A), 1989 -
      1991 (B) and 1999 - 2001 (C), were collected for gender, age, tumour side, method
      of detection, tumour size, tumour type, metastasis, T stage and Fuhrman grade at
      the time of diagnosis. Using the Swedish Cause-of-Death Register, cause-specific
      survival was calculated. When available, tissue was reanalysed according to
      modern standards by an experienced pathologist. RESULTS: The frequency of
      ultrasound and computed tomography increased and autopsy and intravenous
      pyelography decreased with time as the first detection method. There was a
      significant change towards smaller tumours and less severe stages and grades in
      more recent periods. Metastatic disease was most common in the first period. The
      distribution between the different histological tumour types did not change over
      time. Five-year cause-specific survival increased significantly from 41% to 63%.
      Subgroup analysis found significantly increased survival for patients with no
      metastases or with low-grade tumours. CONCLUSION: The data support a true
      decrease in the incidence of RCC over time in Sweden with a migration towards
      lower tumour stages but no change in distribution between the different
      histological subtypes over time.

PMID- 23137103
TI  - Effect of short-term propofol administration on pancreatic enzymes and lipid
      biochemistry in children between 1 month and 36 months.
AB  - BACKGROUND: Use of propofol in pediatric age group has been marred by reports of
      its adverse effects like hypertriglyceridemia and acute pancreatitis, although a
      causal relation has not yet been established. OBJECTIVES: This prospective,
      clinical trial was carried out to evaluate the effects of short-term propofol
      administration on serum lipid profile and serum pancreatic enzymes in children of
      ASA physical status I and II aged between 1 month and 36 months. METHODS:
      Anesthesia was induced with Propofol (1%) in the dose of 3 mg.kg(-1)
      intravenously and was maintained by propofol infusion (0.5%) at the rate of 12
      mg.kg(-1.) h(-1) for the first 20 min and at 8 mg.kg(-1.) h(-1) thereafter. The
      mean dose of propofol administered was 12.02 +/- 2.75 mg.kg(-1) (fat load of
      120.2 +/- 27.5 mg.kg(-1) ). Lipid profile, serum amylase, and lipase were
      measured before induction of anesthesia, at 90 min, 4 h, and finally 24 h after
      induction. RESULTS: Serum lipase levels (P < 0.05), serum triglyceride levels (P
      < 0.05), and serum very low-density lipoproteins VLDL levels (P < 0.05) were
      raised significantly after propofol administration from baseline although
      remained within normal limits. Serum cholesterol levels and serum low-density
      lipoproteins LDL levels showed a statistically significant fall over 24 h. No
      significant changes in serum pancreatic amylase levels were seen (P > 0.05). None
      of the patients developed any clinical features of pancreatitis in the
      postoperative period. CONCLUSION: We conclude that despite a small, transient
      increase in serum triglycerides and pancreatic enzymes, short-term propofol
      administration in recommended dosages in children of ASA status I and II aged
      between 1 month and 36 months does not produce any clinically significant effect
      on serum lipids and pancreatic enzymes.

PMID- 23137104
TI  - Body fat distribution in relation to smoking and exogenous hormones in British
      women.
AB  - OBJECTIVE:  Both cigarette smoking and use of exogenous hormones are associated
      with changes in regional distribution of body fat, but their combined effects are
      less investigated. We examined the interrelation between smoking, exogenous
      hormones and fat distribution in premenopausal and postmenopausal women. METHOD:
      We used data from 20, 962 women without known cardiovascular disease (CVD) who
      were employees of a major department store in Britain. They completed a health
      questionnaire and attended a clinical examination that included waist and hip
      circumference measurements. The cross-sectional analyses were conducted using
      linear regression models. RESULTS: Cigarette smoking, particularly smoking >=20
      cigarettes/day, was associated with larger waist circumference and higher
      waist/hip ratio (WHR) in pre- and postmenopausal women after adjusting for
      potential confounding factors (all P < 0.001). Premenopausal women using combined
      oral contraceptive (COC) and postmenopausal women using oestrogen-only hormone
      replacement therapy (HRT) had lower WHR than non-hormone users in both smokers
      and nonsmokers. However, smokers had higher WHR than nonsmokers in both groups of
      hormone users and nonusers. There was no significant interaction between smoking
      and hormone use in premenopausal and postmenopausal women (P > 0.05). CONCLUSION:
      Although exogenous hormones use was related to a more favourable fat distribution
      in women, smoking was associated with greater abdominal fat accumulation.

PMID- 23137106
TI  - Telmisartan ameliorates insulin sensitivity by activating the AMPK/SIRT1 pathway
      in skeletal muscle of obese db/db mice.
AB  - BACKGROUND: Telmisartan is a well-established angiotensin II type 1 receptor
      blocker that improves insulin sensitivity in animal models of obesity and insulin
      resistance, as well as in humans. Telmisartan has been reported to function as a
      partial agonist of the peroxisome proliferator-activated receptor (PPAR) gamma,
      which is also targeted by the nicotinamide adenine dinucleotide (NAD)-dependent
      deacetylase (SIRT1). Here, we investigated the pathways through which telmisartan
      acts on skeletal muscle, in vitro as well as in vivo. METHODS: Nine-week-old male
      db/db mice were fed a 60% high-fat diet, with orally administrated either vehicle
      (carboxymethyl-cellulose, CMC), 5 mg/kg telmisartan, or 5 mg/kg telmisartan and 1
      mg/kg GW9662, a selective irreversible antagonist of PPARgamma, for 5 weeks.
      Effects of telmisartan on Sirt1 mRNA, AMPK phosphorylation, and NAD+/NADH ratio
      were determined in C2C12 cultured myocytes. RESULTS AND DISCUSSION: Telmisartan
      treatment improved insulin sensitivity in obese db/db mice fed a high-fat diet
      and led to reduction in the size of hypertrophic pancreatic islets in these mice.
      Moreover, in vitro treatment with telmisartan led to increased expression of
      Sirt1 mRNA in C2C12 skeletal muscle cells; the increase in Sirt1 mRNA in
      telmisartan-treated C2C12 myoblasts occurred concomitantly with an increase in
      AMPK phosphorylation, an increase in NAD+/NADH ratio, and increases in the mRNA
      levels of PGC1alpha, FATP1, ACO, and GLUT4. CONCLUSIONS: Our results indicate
      that telmisartan acts through a PPARgamma-independent pathway, but at least
      partially exerts its effects by acting directly on skeletal muscle AMPK/SIRT1
      pathways.

PMID- 23137107
TI  - The enigma of solitary necrotic nodule of the liver.
AB  - BACKGROUND: Solitary necrotic nodule of the liver (SNNL) is a rare benign lesion
      with an uncertain aetiology. There are no typical diagnostic clinical or
      radiological features, and this lesion is usually detected incidentally during
      imaging for other purposes. METHODS: We describe the clinical and radiological
      findings in three patients with histologically confirmed SNNL. The pertinent
      presenting features were documented and subsequent serological testing for
      parasites was performed. RESULTS: All three patients underwent resection because
      it was not possible to exclude a solitary malignancy on preoperative imaging. All
      three nodules had a serpiginous shape with areas of necrosis that showed marked
      staining for eosinophil granules. However, no viable parasites were seen in any
      specimen. There were no specific radiological features that were present in all
      three patients. Two patients had travelled to areas where parasitic infections
      are endemic and one patient had an eosinophilia on presentation. The
      histopathological findings in conjunction with the clinical presentation suggest
      that SNNL may be parasitic in origin. CONCLUSION: The diagnosis of SNNL is
      usually made after surgical excision. A preoperative diagnosis is difficult to
      make even with the use of multiple imaging modalities. The clinical and
      histopathological findings described in our three patients suggest that a
      transient parasitic infection is likely to be the cause in many cases. A history
      of potential exposure to parasites and serological testing for an eosinophilia or
      parasitic antibodies may help make the diagnosis of SNNL without the need for
      resection.

PMID- 23137108
TI  - The characteristics of serious suicide attempters in Japanese adolescents-
      comparison study between adolescents and adults.
AB  - BACKGROUND: Suicide is the leading cause of death among Japanese adolescents, and
      they may commit suicide differently from adults. However, there are few studies
      in medical-based data concerning adolescent patients seriously attempting
      suicide. We aimed to explore the characteristics of serious suicide attempts in
      Japanese adolescents, comparing them with those in adults. METHODS: We
      investigated adolescents who seriously attempted suicide and were treated at the
      Critical Care Medical Center (CCMC) of Nippon Medical School Hospital between
      2000 and 2010, and we compared them with adult suicide attempters treated during
      2009. We retrospectively studied medical records and collected clinical data and
      socio-demographic factors, including age, sex, psychiatric symptoms or diagnosis,
      methods of suicide attempt, motives for suicide attempt, previous deliberate self
      harm, previous psychiatric history, parent loss experience, and previous
      psychiatric history in the family. RESULTS: Adolescent attempters were 15 males
      and 44 females, 13 to 18 years old (mean 16.39). Adult attempters were 37 males
      and 65 females, 19 to 79 years old (mean 39.45). In comparison to adult
      attempters, adolescent attempters were more frequently diagnosed with Borderline
      Personality Disorder (BPD), had more school problems and parent loss experience,
      but they had less financial problems. Gender differences between adolescents and
      adults were examined, and male adolescent attempters were found to be more
      frequently diagnosed with schizophrenia and had less financial problems than
      their adult counterparts, while female adolescent attempters were more frequently
      diagnosed with BPD, had more school problems and parent loss, but they had less
      previous psychiatric history than their adult counterparts. CONCLUSIONS: Our
      findings indicated that adolescent attempters were more frequently diagnosed with
      BPD and had more school problems and parent loss experience but had less
      financial problems. Additionally, in male adolescent attempters, identifying
      patients with schizophrenia seemed important, as it was their most frequent
      psychiatric diagnosis. For female adolescents, adequately assessing family
      function and interpersonal conflicts seemed important, as they were more often
      diagnosed with BPD and had more school and family problems.

PMID- 23137109
TI  - Single-port laparoscopic colorectal surgery: early clinical experience.
AB  - BACKGROUND: Single-port laparoscopic surgery (SPLS) for colorectal pathology is
      an advanced technique wherein laparoscopic surgery is carried out through a
      single small incision hidden in the umbilicus. Advantages of this technique over
      standard laparoscopy are still under investigation. This study reports the
      initial experience and short-term outcomes of colorectal SPLS procedures in a
      single academic-based institution. SUBJECTS AND METHODS: All patients who
      underwent SPLS for colorectal procedures between February 2010 and March 2011
      were recruited into this prospective study. Patients' demographics, pathology,
      and intraoperative and postoperative outcomes were collected. Time to first
      flatus and bowel movement, postoperative pain, duration of hospital stay, and
      complications were also measured. RESULTS: Twenty patients underwent colorectal
      SPLS: 17 patients underwent right hemicolectomy, and 3 patients had sigmoid
      resection. Mean age was 66+/-14 years, and body mass index was 25+/-4 kg/m(2).
      Median operative time for right hemicolectomy was 120 minutes (range, 110-136
      minutes), and that for sigmoid resection was 158 minutes (range, 86-177 minutes).
      Mean measured incision length was 4.2+/-1.2 cm (range, 2.5-7 cm). Two cases were
      converted to standard multiport laparoscopy, and 1 was converted to open surgery
      Postoperatively, there was no mortality. Intra-abdominal abscess was observed in
      3 patients. Median postoperative stay was 3 days (range, 3-3 days). Median number
      of lymph nodes extracted was 15 (range, 12-23). CONCLUSIONS: The SPLS is
      technically feasible with proper patient selection for a variety of applications
      in colorectal surgery. Improvement in instrumentation and technology is likely to
      expand the role of SPLS in minimally invasive surgery. It is important to audit
      outcomes as this novel approach is introduced.

PMID- 23137110
TI  - Commentary on "Single-port laparoscopic colorectal surgery: early clinical
      experience".

PMID- 23137111
TI  - Commentary on "Day-case laparoscopic Nissen fundoplication: a default pathway or
      is selection the key?".

PMID- 23137112
TI  - Commentary on "Modified techniques and early outcomes of totally laparoscopic
      total gastrectomy with side-to-side esophagojejunostomy".

PMID- 23137113
TI  - Video-assisted thoracoscopic surgery to treat hydatid disease of the thorax in
      adults: is it feasible?
AB  - BACKGROUND: Optimal treatment of intrathoracic hydatid diseases in adults
      involves complete removal of the cyst with parenchyma-preserving surgery. In
      current practice, thoracotomy remains the standard surgical approach for
      pulmonary hydatid cysts, so surgical experience is limited, particularly with
      regard to video-assisted thoracoscopic surgery (VATS). SUBJECTS AND METHODS:
      Between June 2007 and May 2011, a selected series of 12 adult patients presenting
      with intrathoracic hydatid cysts underwent VATS. The cysts were completely
      removed using a three-trocar technique. RESULTS: Complete removal of the cysts
      was successful in all patients. All cysts were diagnosed by computerized
      tomography, and 6 (50%) patients had a history of hydatid disease in the liver or
      lung. No serious postoperative complications were observed. Patients with
      thoracoscopic excision were discharged after a median of 2.9 days (range, 2-6
      days). No recurrences or complications were observed during a mean follow-up of
      29 months. CONCLUSIONS: Considering the conversion and complication rates in our
      series, VATS should be the primary therapeutic choice for adults with thoracic
      hydatid cysts. Open surgical interventions in patients with large and
      uncomplicated cysts appear optional.

PMID- 23137114
TI  - Totally laparoscopic total gastrectomy using endoscopic linear stapler: early
      experiences at one institute.
AB  - BACKGROUND: Totally laparoscopic total gastrectomy (TLTG) for gastric cancer is
      still uncommon because of the technical difficulty of performing the
      esophagojejunostomy laparoscopically. We have developed a secure technique for
      intracorporeal esophagojejunostomy and successfully performed the TLTG method
      using an endoscopic linear stapler. Our experiences with this method are reported
      here. SUBJECTS AND METHODS: Between July 2009 and May 2010, 124 patients with
      gastric cancer underwent TLTG using endoscopic linear staplers in one
      institution. The clinicopathological data and surgical outcomes of the first 70
      cases and the subsequent 54 cases were reviewed retrospectively and compared
      because technical improvements were instituted after the 70th case. RESULTS: The
      two groups differed significantly in terms of mean operation time (189.0 versus
      148.3 minutes, P<.001), overall postoperative complication rate (37.1% versus
      13.0%, P=.003), severe postoperative complication rate (15.7% versus 3.7%,
      P=.030), and intraoperative event rate (12.9% versus 1.9%, P=.042). CONCLUSIONS:
      The early period of performing TLTG using an endoscopic linear stapler was
      associated with a high morbidity rate. This improved significantly when key
      technical changes were introduced. However, surgeons who are inexperienced in
      laparoscopic gastrectomy should be careful when performing TLTG because it
      involves many complex processes. The account in this report of our experiences
      with TLTG may help surgeons to master this method faster and more safely.

PMID- 23137115
TI  - Commentary on "Totally laparoscopic total gastrectomy using endoscopic linear
      stapler: early experiences at one institute".

PMID- 23137116
TI  - Intraoperative use of the vacuum bell for elevating the sternum during the Nuss
      procedure.
AB  - OBJECTIVE: To evaluate the routine use of the vacuum bell for elevating the
      sternum during minimally invasive repair of pectus excavatum (MIRPE) (the Nuss
      procedure). SUBJECTS AND METHODS: This was a retrospective evaluation of a
      prospective database including all patients who underwent MIRPE at our
      institution between 2005 and 2010. Data included the patient's demographic
      characteristics, age at surgery, gender, Haller index, duration of surgery, and
      intraoperative complications. RESULTS: Fifty patients from 9 to 28 years old
      (average, 14.95 years) were observed, including 39 males and 11 females. The
      preoperative Haller index was between 3.25 and 7.4 (average, 5.05). Mean duration
      of surgery was 58 minutes (range, 45-92 minutes). The use of the vacuum bell led
      to a clear elevation of the sternum as confirmed by thoracoscopy. Advancement of
      the pectus introducer and placement of the pectus bar were safe, successful, and
      uneventful in all patients. No cardial and/or pericardial lesion was noted as
      well as no lesion of the mammary vessels. CONCLUSIONS: The intraoperative use of
      the vacuum bell during the MIRPE is safe and effective as it facilitates the
      retrosternal dissection and the insertion of the pectus bar. If available, we
      recommend the routine use of this device for MIRPE.

PMID- 23137117
TI  - Cortisol response to experimental pain in patients with chronic low back pain and
      patients with major depression.
AB  - OBJECTIVE: Chronic pain and major depression have been associated with
      alterations of the hypothalamus-pituitary-adrenal axis (HPA) activity. Previous
      studies suggested that HPA activity is diminished in chronic pain but increased
      in depression. However, little is known about the effects of experimentally
      induced acute pain on cortisol secretion in patients with chronic pain and
      depression. METHODS: On three different occasions (day 1, day 8, day 90), we
      repeatedly examined 20 patients with chronic low back pain without depression, 22
      patients with major depression without pain, and 33 healthy subjects using heat
      stimuli. Pain intensity was rated by participants using a visual analog scale.
      Salivary cortisol was assessed prior to 10 blocks of repeated painful heat
      stimuli, and 45 and 60 minutes afterwards. RESULTS: In repeated measures analyses
      of covariance adjusting for age, sex, and time of examination, we found a
      significant effect of group (P < 0.01) and post-hoc tests confirmed that patients
      with chronic pain had lower cortisol area-under-the-curve values compared with
      healthy controls and depressed patients at all time points (all P values <0.01).
      However, cortisol secretion in depressed patients did not differ from controls.
      CONCLUSIONS: Across groups, experimental heat pain stimuli did not elicit a
      significant cortisol response. Chronic pain appears to be associated with low
      cortisol secretion. The mechanisms linking chronic pain with low cortisol deserve
      further study.

PMID- 23137118
TI  - Halogen bonding inside a molecular container.
AB  - The synthetic macrocycle cucurbit[6]uril forms host-guest inclusion complexes
      with molecular dibromine and diiodine. As evidenced by their crystal structures,
      the encapsulated dihalogens adapt a tilted axial geometry and are held in place
      by two different types of halogen-bonding interactions, one with a water molecule
      (bond distances 2.83 A for O...Br and 3.10 A for O...I) and the other one with
      the ureido carbonyl groups of the molecular container itself (bond distances 3.33
      A for O...Br and 3.49 A for O...I). While the former is of the conventional type,
      involving the lone electron pair of an oxygen donor, the latter is perpendicular,
      involving the pi-system of the carbonyl oxygen (N-C?O...X dihedrals ca. 90
      degrees ). Such perpendicular interactions resemble those observed in protein
      complexes of halogenated ligands. A statistical analysis of small-molecule
      crystal structural data, as well as quantum-chemical calculations with urea as a
      model (MP2/aug-cc-pVDZ-PP), demonstrates that halogen bonding with the pi-system
      of the carbonyl oxygen can become competitive with the commonly favored lone-pair
      interaction whenever the carbonyl group carries electron-donating substitutents,
      specifically for ureas, amides, and esters, and particularly when the lone pairs
      are engaged in orthogonal hydrogen bonding (hX bonds). The calculations further
      demonstrate that the perpendicular interactions remain significantly attractive
      also for nonlinear distortions of the O...X-X angle to ca. 140 degrees , the
      angle observed in the two reported crystal structures. The structural and
      theoretical data jointly support the assignment of the observed dihalogen
      carbonyl contacts as genuine halogen bonds.

PMID- 23137119
TI  - Combined liver transplantation and gastric sleeve resection for patients with
      medically complicated obesity and end-stage liver disease.
AB  - Obesity is increasingly common before and after liver transplantation (LT), yet
      optimal management remains unclear. Our aim was to analyze the effectiveness of a
      multidisciplinary protocol for obese patients requiring LT, including a
      noninvasive pretransplant weight loss program, and a combined LT plus sleeve
      gastrectomy (SG) for obese patients who failed to lose weight prior to LT. Since
      2006, all patients referred LT with a BMI > 35 were enrolled. There were 37
      patients who achieved weight loss and underwent LT alone, and 7 who underwent LT
      combined with SG. In those who received LT alone, weight gain to BMI > 35 was
      seen in 21/34, post-LT diabetes (DM) in 12/34, steatosis in 7/34, with 3 deaths
      plus 3 grafts losses. In patients undergoing the combined procedure, there were
      no deaths or graft losses. One patient developed a leak from the gastric staple
      line, and one had excess weight loss. No patients developed post-LT DM or
      steatosis, and all had substantial weight loss (mean BMI = 29). Noninvasive
      pretransplant weight loss was achieved by a majority, though weight gain post-LT
      was common. Combined LT plus SG resulted in effective weight loss and was
      associated with fewer post-LT metabolic complications. Long-term follow-up is
      needed.

PMID- 23137120
TI  - Transformation of adrenal medullary chromaffin cells increases asthmatic
      susceptibility in pups from allergen-sensitized rats.
AB  - BACKGROUND: Studies have shown that epinephrine release is impaired in patients
      with asthma. The pregnancy of female rats (dams) with asthma promotes in their
      pups the differentiation of adrenal medulla chromaffin cells (AMCCs) into
      sympathetic neurons, mediated by nerve growth factor, which leads to a reduction
      in epinephrine secretion. However, the relatedness between the alteration of
      AMCCs and increased asthma susceptibility in such offspring has not been
      established. METHODS: In this study, we observed the effects of allergization via
      ovalbumin on rat pups born of asthmatic dams. RESULTS: Compared to the offspring
      of untreated controls, bronchial hyperreactivity and airway inflammation were
      more severe in the pups from sensitized (asthmatic) dams. In pups exposed to
      nerve growth factor (NGF) in utero these effects were aggravated further, but the
      effects were blocked in pups whose dams had been treated with anti-NGF.
      Furthermore, alterations in AMCC phenotype corresponded to the degree of
      bronchial hyperreactivity and lung lesions of the different treatment groups.
      Such AMCC alterations included degranulation of chromaffin granules, reduction of
      epinephrine and phenylethanolamine-n-methyl transferase, and elevation of NGF and
      peripherin levels. CONCLUSIONS: Our results present evidence that asthma during
      the pregnancy of rat dams promotes asthma susceptibility in their offspring, and
      that the transformation of AMCCs to neurons induced by NGF plays an important
      role in this process.

PMID- 23137121
TI  - The use of contact lenses during water-polo play: a 20-year study of Japanese
      college players.
AB  - This study investigated the extent of contact-lens use in Japanese college water
      polo male players over 20 years (1991-2011, once every five years). Information
      about the use of contact lenses during play and the types of contact lens was
      obtained through a self-report questionnaire. The proportion of contact lens use
      among the players while playing water polo differed from 1991 to 2011 (chi2(4) =
      25.28, P < 0.001, Cohen's d = 0.63). Fifty-four per cent of the players used
      contact lenses while playing in 1991 (P < 0.001); more than 74% in 1996; 89% in
      2001; 84% in 2006; and 86% in 2011. While 96% of the contact lenses used by the
      players in 1991 were the soft type, 74%, 92%, 86%, and 88% of the contact lenses
      used in 1996, 2001, 2006, and 2011, respectively, were the disposable type. These
      findings indicated a high percentage of players were using contact lenses while
      playing water polo between 1996 and 2011. This could be because the majority of
      players used disposable lenses. The results suggest that increasing use of
      contact lenses by water-polo players is beneficial.

PMID- 23137122
TI  - Long-term follow-up assessment of a phase 1 trial of angiogenic gene therapy
      using direct intramyocardial administration of an adenoviral vector expressing
      the VEGF121 cDNA for the treatment of diffuse coronary artery disease.
AB  - On the basis of studies in experimental animals demonstrating that AdVEGF121, an
      E1(-)E3(-) serotype 5 adenovirus coding the 121 isoform of vascular endothelial
      growth factor (VEGF), could mediate the generation of new blood vessels and
      reverse coronary ischemia, a clinical study of direct myocardial administration
      of AdVEGF121 was initiated in patients with late-stage, diffuse coronary artery
      disease. This study provides long-term (median, 11.8 years) follow-up on these
      patients. From 1997 to 1999, AdVEGF121 was administered by direct myocardial
      injection to an area of reversible ischemia in 31 patients with severe coronary
      disease, either as an adjunct to conventional coronary artery bypass grafting
      (group A) or as minimally invasive sole (MIS) therapy, using a minithoracotomy
      (group B). There was no control group; the study participants served as the
      control subjects. The 5- and 10-year survival was 10 of 15 (67%) and 6 of 15
      (40%) for the group A patients, and 11 of 16 (69%) and 5 of 16 (31%) for group B
      sole therapy patients, respectively. In comparison, maximal medical therapy in
      comparable groups in the literature have a 3- to 5-year survival rate of 52 to
      59%. For the survivors, the angina score for group A was 3.4+/-0.5 at time 0 and
      1.9+/-1.0 at last follow-up, and for group B it was 3.4+/-0.6 and 2.0+/-1.1,
      respectively. The incidences of malignancy and retinopathy were no greater than
      that expected for the age-matched general population. We conclude that adenovirus
      mediated VEGF direct myocardial administration to patients with severe coronary
      artery disease is safe, and future larger trials are warranted to assess
      efficacy.

PMID- 23137123
TI  - New antifeedant C20 terpenoids from Leucosceptrum canum.
AB  - Three novel C(20) terpenoids, norleucosceptroids A-C (1-3), were isolated from
      the leaves and flowers of Leucosceptrum canum (Labiatae) and were identified by
      comprehensive spectroscopic analysis and, in the case of 1, single-crystal X-ray
      diffraction. Structurally, compounds 1-3 should be categorized as pentanor
      sesterterpenoids rather than diterpenoids. Moderate antifeedant activity of 1-3
      against the generalist plant-feeding insect Helicoverpa armigera was detected,
      suggesting that they might also be involved in the plant defense against insect
      herbivores.

PMID- 23137124
TI  - Embodying sexual subjectivity after cancer: a qualitative study of people with
      cancer and intimate partners.
AB  - Research has increasingly recognised the profound impact that cancer can have
      upon embodied subjectivity. However, there has been little acknowledgement of the
      centrality of sexuality to subjectivity, and marginalisation of the experiences
      of intimate partners of people with cancer. This Australian qualitative study
      explores the post-cancer experiences of embodied sexual subjectivity for 44
      people with cancer (23 women and 21 men) and 35 partners of people with cancer
      (18 women and 17 men) across a range of cancer types and stages. Semi-structured
      interviews were analysed with theoretical thematic analysis, guided by a post
      structuralist approach to sexual subjectivity as a dynamic process of becoming
      that can change over time, and by Williams' [(1996). The vicissitudes of
      embodiment across the chronic illness trajectory. Body and Society, 2, 23-47]
      framework on post-illness embodiment. Participants took up the following post
      cancer subject positions: 'dys-embodied sexual subjectivity' - characterised by
      bodily betrayal, sexual loss, lack of acceptance, depression, and anxiety; 're
      embodied sexual subjectivity'--characterised by greater sexual confidence,
      acceptance, the exploration of non-coital sexual practices and increased
      relational closeness; and 'oscillating sexual subjectivity'--involving a shift
      between states of sexual dys-embodiment and sexual re-embodiment. The findings
      point to the importance of focusing on the sexual health of people with cancer
      and partners across the cancer trajectory.

PMID- 23137126
TI  - Current prospects for interferon-free treatment of hepatitis C in 2012.
AB  - Present interferon-based therapy for chronic hepatitis C is limited by both
      efficacy and tolerability. Telaprevir and boceprevir are the first two direct
      acting antiviral drugs (DAAs) that inhibit hepatitis C virus replication to be
      licensed for use in conjunction with pegylated interferon and ribavirin. Numerous
      other DAAs are in clinical development, and phases 2 and 3 trials are evaluating
      interferon-free combination DAA therapy. Interferon-free sustained virologic
      responses have now been achieved with combinations of asunaprevir and
      daclatasvir; sofosbuvir and ribavirin; sofosbuvir and daclatasvir; faldaprevir
      and BI207127; ABT-450, ritonovir and ABT-333; ABT-450, ritonovir and ABT-072;
      miracitabine, danoprevir and ritonavir; and alisporivir and ribavirin. Some drugs
      are genotype-specific in their activity, whereas others are pan-genotypic, and
      differential responses for the genotype 1 subtypes 1a and 1b have emerged with
      many DAA combinations. Viral breakthrough and resistance are important
      considerations for future trial design. The prospect of interferon-free
      combination DAA therapy for hepatitis C virus is now finally becoming a reality.

PMID- 23137127
TI  - The effect of electromagnetic field on reactive oxygen species production in
      human neutrophils in vitro.
AB  - The present study was undertaken in order to determine the effect of low
      frequency electromagnetic field (EMF) on reactive oxygen species (ROS) production
      in human neutrophils in peripheral blood in vitro. We investigated how
      differently generated EMF and several levels of magnetic induction affect ROS
      production. To evaluate the level of ROS production, two fluorescent dyes were
      used: 2'7'-dichlorofluorscein-diacetate and dihydrorhodamine. Phorbol 12
      myristate 13-acetate (PMA), known as strong stimulator of the respiratory burst,
      was also used. Alternating magnetic field was generated by means of Viofor JPS
      apparatus. Three different levels of magnetic induction have been analyzed (10,
      40 and 60 MUT). Fluorescence of dichlorofluorescein and 123 rhodamine was
      measured by flow cytometry. The experiments demonstrated that only EMF tuned to
      the calcium ion cyclotron resonance frequency was able to affect ROS production
      in neutrophils. Statistical analysis showed that this effect depended on magnetic
      induction value of applied EMF. Incubation in EMF inhibited cell activity
      slightly in unstimulated neutrophils, whereas the activity of PMA-stimulated
      neutrophils has increased after incubation in EMF. 

PMID- 23137129
TI  - Crystal structures of wild-type and mutated cyclophilin B that causes
      hyperelastosis cutis in the American quarter horse.
AB  - BACKGROUND: Hyperelastosis cutis is an inherited autosomal recessive connective
      tissue disorder. Affected horses are characterized by hyperextensible skin,
      scarring, and severe lesions along the back. The disorder is caused by a mutation
      in cyclophilin B. RESULTS: The crystal structures of both wild-type and mutated
      (Gly6->Arg) horse cyclophilin B are presented. The mutation neither affects the
      overall fold of the enzyme nor impairs the catalytic site structure. Instead, it
      locally rearranges the flexible N-terminal end of the polypeptide chain and also
      makes it more rigid. CONCLUSIONS: Interactions of the mutated cyclophilin B with
      a set of endoplasmic reticulum-resident proteins must be affected.

PMID- 23137130
TI  - N-acylated dipeptide tags enable precise measurement of ion temperature in
      peptide fragmentation.
AB  - Peptide fragmentations into b- and y-type ions are useful for the identification
      of proteins. The b ion, having the structure of a N-protonated oxazolone,
      dissociates to the a-type ion with loss of CO. This CO-loss process affords the
      possibility of characterizing the temperature of the b ion. Herein, we used N
      acylated dipeptide tags, isobaric tags originally developed for protein
      quantification, as internal standards for the measurement of the ion temperature
      in peptide fragmentation. Amine-reactive dipeptide tags were attached to the N
      termini of sample peptides. Collision-induced dissociation (CID) of the tagged
      peptides yielded a b-type quantitation signal (b(S)) from the tag, which
      subsequently dissociated into the a(S) ion with CO-loss. As the length of alkyl
      side chain on the dipeptide tag was extended from C(1) to C(8), the yield of a(S)
      ion gradually increased for the 4-alkyl-substituted oxazolone ion but decreased
      for the 2-alkyl-substituted one. To gain insights into the unimolecular
      dissociation kinetics, we obtained the potential energy surface from ab initio
      calculations. Theoretical study suggested that the 4-alkyl substitution on N
      protonated oxazolone decreased the enthalpy of activation by stabilizing the
      productlike transition state, whereas the 2-alkyl substitution increased it by
      stabilizing the reactant. Resulting potential energy surfaces were used to
      calculate the microcanonical and canonical rate constants as well as the a(S)-ion
      yield. Arrhenius plots of canonical rate constants provided activation energies
      and pre-exponential factors for the CO-loss processes in the 600-800 K range.
      Comparison of experimental a(S)-ion yields with theoretical values led to precise
      determination of the temperature of b(S) ion. Thus, the b(S)-ion temperature of
      tagged peptide can be measured simply by combining kinetic parameters provided
      here and a(S)-ion yields obtained experimentally. Although the b-type fragment
      patterns varied with the chain length and position of alkyl substituent on the N
      protonated oxazolone, the y-type fragment patterns were almost identical under
      these conditions. Furthermore, b(S)-ion temperatures were nearly the same with
      only a few degrees K difference. Our results demonstrate a novel use of N
      acylated dipeptide tags as internal temperature standards, which enables the
      reproducible acquisition of peptide fragment spectra.

PMID- 23137131
TI  - Evaluation of exclusion prenatal and exclusion preimplantation genetic diagnosis
      for Huntington's disease in the Netherlands.
AB  - Individuals at 50% risk of Huntington's disease (HD) who prefer not to know their
      carrier status, might opt for exclusion prenatal diagnosis (ePND) or exclusion
      preimplantation genetic diagnosis (ePGD). This study aims to provide a better
      understanding of couples' motives for choosing ePND or ePND, and surveys couples'
      experiences in order to make recommendations for the improvement of counselling
      for exclusion testing. This qualitative retrospective interview study focussed on
      couples who underwent ePND or ePGD for HD in the period 1996-2010. Seventeen
      couples were included of which 13 had experienced ePND and 6 ePGD. Mean time
      interval since exclusion-testing was 3.9 years. Couples' moral reservations
      regarding termination of pregnancy (TOP) or discarding healthy embryos were
      counterbalanced by the wish to protect their future child against HD. Seven
      couples had terminated a total of 11 pregnancies with a 50% HD risk, none showed
      regret. ePGD was used by couples who wanted to avoid (another) TOP. ePND and ePGD
      are acceptable reproductive options for a specific group of counsellees. To
      guarantee sound standards of care, it is imperative that candidate couples be
      given in-depth non-directive counselling about all possible scenarios, and
      adequate professional and psychological support prior to, during and after
      ePND/ePGD.

PMID- 23137132
TI  - Patient and tumour-related factors for prediction of urinary incontinence after
      radical prostatectomy.
AB  - OBJECTIVE: The aim of this study was to identify preoperative patient and tumour
      related factors associated with 12 months postoperative urinary incontinence.
      MATERIAL AND METHODS: In total, 1529 men who had undergone radical prostatectomy
      for clinically localized prostate cancer between September 2008 and February 2010
      at 15 Swedish hospitals completed a questionnaire before, 3 and 12 months after
      surgery. Urinary leakage, comorbidity and possible confounders were measured by
      self-administered validated questionnaires. Clinical data were collected
      preoperatively and postoperatively. The primary outcome, incontinence, was
      defined as the change of one pad or more per day. The ratio of proportions,
      estimated according to the log-binomial regression model, was analysed for 38
      different factors and is presented as relative risks with 95% confidence
      intervals. Age-adjusted relative risk was calculated in the corresponding
      bivariate regression model. Results. Prospective data were available from 1360
      men (response rate 89%). Results showed that age at surgery predicts long-term
      urinary incontinence exponentially. Patients reporting urinary leakage before
      prostate cancer diagnosis had an age-adjusted relative risk of 1.8 (95%
      confidence interval 1.3-2.4) for incontinence 12 months postoperatively. No
      statistically significant correlation was found between previous transurethral
      resection of the prostate, high body mass index or the other 34 evaluated factors
      and postoperative incontinence. CONCLUSIONS: Of 38 possible risk factors only age
      at surgery and preoperative urinary leakage were associated with 12 months
      postoperative incontinence in this study comprising 1360 men operated with
      radical prostatectomy. These findings may help the surgeon to have a targeted
      risk conversation with the patient before the treatment decision is made.

PMID- 23137133
TI  - ESCMID* guideline for the diagnosis and management of Candida diseases 2012:
      developing European guidelines in clinical microbiology and infectious diseases.
AB  - The process to develop a guideline in a European setting remains a challenge. The
      ESCMID Fungal Infection Study Group (EFISG) successfully achieved this endeavour.
      After two face-to-face meetings, numerous telephone conferences, and email
      correspondence, an ESCMID task force (basically composed of members of the
      Society's Fungal Infection Study Group, EFISG) finalized the ESCMID diagnostic
      and management/therapeutic guideline for Candida diseases. By appreciating
      various patient populations at risk for Candida diseases, four subgroups were
      predefined, mainly ICU patients, paediatric, HIV/AIDS and patients with
      malignancies including haematopoietic stem cell transplantation. Besides
      treatment recommendations, the ESCMID guidelines provide guidance for diagnostic
      procedures. For the guidelines, questions were formulated to phrase the intention
      of a given recommendation, for example, outcome. The recommendation was the
      clinical intervention, which was graded by a score of A-D for the 'Strength of a
      recommendation'. The 'level of evidence' received a score of I-III. The author
      panel was approved by ESCMID, European Organisation for Research and Treatment of
      Cancer, European Group for Blood and Marrow Transplantation, European Society of
      Intensive Care Medicine and the European Confederation of Medical Mycology. The
      guidelines followed the framework of GRADE and Appraisal of Guidelines, Research,
      and Evaluation. The drafted guideline was presented at ECCMID 2011 and points of
      discussion occurring during that meeting were incorporated into the manuscripts.
      These ESCMID guidelines for the diagnosis and management of Candida diseases
      provide guidance for clinicians in their daily decision-making process.

PMID- 23137134
TI  - ESCMID* guideline for the diagnosis and management of Candida diseases 2012:
      diagnostic procedures.
AB  - As the mortality associated with invasive Candida infections remains high, it is
      important to make optimal use of available diagnostic tools to initiate
      antifungal therapy as early as possible and to select the most appropriate
      antifungal drug. A panel of experts of the European Fungal Infection Study Group
      (EFISG) of the European Society of Clinical Microbiology and Infectious Diseases
      (ESCMID) undertook a data review and compiled guidelines for the clinical utility
      and accuracy of different diagnostic tests and procedures for detection of
      Candida infections. Recommendations about the microbiological investigation and
      detection of candidaemia, invasive candidiasis, chronic disseminated candidiasis,
      and oropharyngeal, oesophageal, and vaginal candidiasis were included. In
      addition, remarks about antifungal susceptibility testing and therapeutic drug
      monitoring were made.

PMID- 23137135
TI  - ESCMID* guideline for the diagnosis and management of Candida diseases 2012: non
      neutropenic adult patients.
AB  - This part of the EFISG guidelines focuses on non-neutropenic adult patients. Only
      a few of the numerous recommendations can be summarized in the abstract.
      Prophylactic usage of fluconazole is supported in patients with recent abdominal
      surgery and recurrent gastrointestinal perforations or anastomotic leakages.
      Candida isolation from respiratory secretions alone should never prompt
      treatment. For the targeted initial treatment of candidaemia, echinocandins are
      strongly recommended while liposomal amphotericin B and voriconazole are
      supported with moderate, and fluconazole with marginal strength. Treatment
      duration for candidaemia should be a minimum of 14 days after the end of
      candidaemia, which can be determined by one blood culture per day until
      negativity. Switching to oral treatment after 10 days of intravenous therapy has
      been safe in stable patients with susceptible Candida species. In candidaemia,
      removal of indwelling catheters is strongly recommended. If catheters cannot be
      removed, lipid-based amphotericin B or echinocandins should be preferred over
      azoles. Transoesophageal echocardiography and fundoscopy should be performed to
      detect organ involvement. Native valve endocarditis requires surgery within a
      week, while in prosthetic valve endocarditis, earlier surgery may be beneficial.
      The antifungal regimen of choice is liposomal amphotericin B +/- flucytosine. In
      ocular candidiasis, liposomal amphotericin B +/- flucytosine is recommended when
      the susceptibility of the isolate is unknown, and in susceptible isolates,
      fluconazole and voriconazole are alternatives. Amphotericin B deoxycholate is not
      recommended for any indication due to severe side effects.

PMID- 23137136
TI  - ESCMID* guideline for the diagnosis and management of Candida diseases 2012:
      prevention and management of invasive infections in neonates and children caused
      by Candida spp.
AB  - Invasive candidiasis (IC) is a relatively common syndrome in neonates and
      children and is associated with significant morbidity and mortality. These
      guidelines provide recommendations for the prevention and treatment of IC in
      neonates and children. Appropriate agents for the prevention of IC in neonates at
      high risk include fluconazole (A-I), nystatin (B-II) or lactoferrin +/-
      Lactobacillus (B-II). The treatment of IC in neonates is complicated by the high
      likelihood of disseminated disease, including the possibility of infection within
      the central nervous system. Amphotericin B deoxycholate (B-II), liposomal
      amphotericin B (B-II), amphotericin B lipid complex (ABLC) (C-II), fluconazole (B
      II), micafungin (B-II) and caspofungin (C-II) can all be potentially used.
      Recommendations for the prevention of IC in children are largely extrapolated
      from studies performed in adults with concomitant pharmacokinetic data and models
      in children. For allogeneic HSCT recipients, fluconazole (A-I), voriconazole (A
      I), micafungin (A-I), itraconazole (B-II) and posaconazole (B-II) can all be
      used. Similar recommendations are made for the prevention of IC in children in
      other risk groups. With several exceptions, recommendations for the treatment of
      IC in children are extrapolated from adult studies, with concomitant
      pharmacokinetic studies. Amphotericin B deoxycholate (C-I), liposomal
      amphotericin B (A-I), ABLC (B-II), micafungin (A-I), caspofungin (A-I),
      anidulafungin (B-II), fluconazole (B-I) and voriconazole (B-I) can all be used.

PMID- 23137137
TI  - ESCMID* guideline for the diagnosis and management of Candida diseases 2012:
      adults with haematological malignancies and after haematopoietic stem cell
      transplantation (HCT).
AB  - Fungal diseases still play a major role in morbidity and mortality in patients
      with haematological malignancies, including those undergoing haematopoietic stem
      cell transplantation. Although Aspergillus and other filamentous fungal diseases
      remain a major concern, Candida infections are still a major cause of mortality.
      This part of the ESCMID guidelines focuses on this patient population and reviews
      pertaining to prophylaxis, empirical/pre-emptive and targeted therapy of Candida
      diseases. Anti-Candida prophylaxis is only recommended for patients receiving
      allogeneic stem cell transplantation. The authors recognize that the
      recommendations would have most likely been different if the purpose would have
      been prevention of all fungal infections (e.g. aspergillosis). In targeted
      treatment of candidaemia, recommendations for treatment are available for all
      echinocandins, that is anidulafungin (AI), caspofungin (AI) and micafungin (AI),
      although a warning for resistance is expressed. Liposomal amphotericin B received
      a BI recommendation due to higher number of reported adverse events in the
      trials. Amphotericin B deoxycholate should not be used (DII); and fluconazole was
      rated CI because of a change in epidemiology in some areas in Europe. Removal of
      central venous catheters is recommended during candidaemia but if catheter
      retention is a clinical necessity, treatment with an echinocandin is an option
      (CII(t) ). In chronic disseminated candidiasis therapy, recommendations are
      liposomal amphotericin B for 8 weeks (AIII), fluconazole for >3 months or other
      azoles (BIII). Granulocyte transfusions are only an option in desperate cases of
      patients with Candida disease and neutropenia (CIII).

PMID- 23137138
TI  - ESCMID* guideline for the diagnosis and management of Candida diseases 2012:
      patients with HIV infection or AIDS.
AB  - Mucosal candidiasis is frequent in immunocompromised HIV-infected highly active
      antiretroviral (HAART) naive patients or those who have failed therapy. Mucosal
      candidiasis is a marker of progressive immune deficiency. Because of the
      frequently marked and prompt immune reconstitution induced by HAART, there is no
      recommendation for primary antifungal prophylaxis of mucosal candidiasis in the
      HIV setting in Europe, although it has been evidenced as effective in the pre
      HAART era. Fluconazole remains the first line of therapy for both oropharyngeal
      candidiasis and oesophageal candidiasis and should be preferred to itraconazole
      oral solution (or capsules when not available) due to fewer side effects. For
      patients who still present with fluconazole-refractory mucosal candidiasis, oral
      treatment with any other azole should be preferred based on precise Candida
      species identification and susceptibility testing results in addition to the
      optimization of HAART when feasible. For vaginal candidiasis, topical therapy is
      preferred.

PMID- 23137139
TI  - Effects of montelukast and zileuton on testicular torsion/detorsion injury in
      rats.
AB  - The aim of this study was to evaluate and compare the effects of 5-lipoxygenase
      enzyme (5-LO) inhibitor zileuton and cysteinyl leukotriene receptor (CysLT1R)
      antagonist montelukast in testicular torsion/detorsion (T/D) injury model in
      rats. Rats were anaesthetised with 75 mg kg(-1) ketamine hydrochloride and 8 mg
      kg(-1) xylazine intraperitoneal before the operation. Torsion was created by
      rotating the right testis 720 degrees  clockwise and maintained by fixing the
      testis. The rats were treated with CysLT1R antagonist montelukast (10 mg kg(-1);
      i.p.), 5-LO inhibitor zileuton (3 mg kg(-1); i.p.), and vehicle, at 30 min prior
      detorsion. After 1 h of torsion, the testis was counter-rotated to the natural
      position and replaced into the scrotum. Malondialdehyde (MDA) level was measured
      in testicular tissue after 3 h of reperfusion. Histological examination was
      performed after 24 h of reperfusion. T/D caused a significant increase in MDA
      level and histopathological injury in testes. Montelukast and zileuton treatments
      prevented the T/D-induced augmentation in MDA levels. Only zileuton treatment
      significantly reduced the T/D-induced histopathological injury. In this study, we
      demonstrated for the first time that zileuton had protective effects on
      testicular T/D injury. We have also found that zileuton is more effective than
      montelukast on histopathological injury.

PMID- 23137141
TI  - The Affordable Medicines Facility-malaria--a success in peril.
AB  - The Affordable Medicines Facility-malaria (AMFm) has put into place a bold
      financing plan for artemisinin-combination therapy in a pilot phase in seven
      countries covering half the population at risk of malaria in Africa. A report of
      the AMFm independent evaluation, conducted by ICF International and the London
      School of Hygiene and Tropical Medicine, describes the success of the programme
      in the pilot sites: Ghana, Kenya, Madagascar, Niger, Nigeria, Tanzania (mainland
      and Zanzibar) and Uganda, comparing availability and affordability of high
      quality artemisinin-combination therapies before and after AMFm launched. Proof
      of concept was achieved: AMFm increased availability and kept prices low, meeting
      its initial, ambitious benchmarks in most settings. Despite this overwhelming
      success, opposition to the programme and dwindling resources for malaria control
      conspire to cripple or kill AMFm.

PMID- 23137142
TI  - Quantifying the roles of ecology and geography in spatial genetic divergence.
AB  - Investigating the properties of ecological landscapes that influence gene flow
      among populations can provide key insights into the earliest stages of biological
      divergence. Both ecological and geographical factors can reduce gene flow, which
      can lead to population divergence, but we know little of the relative strengths
      of these phenomena in nature. Here, we use a novel application of structural
      equation modelling to quantify the contributions of ecological and geographical
      isolation to spatial genetic divergence in 17 species of Anolis lizards. Our
      comparative analysis shows that although both processes contributed
      significantly, geographical isolation explained substantially more genetic
      divergence than ecological isolation (36.3 vs. 17.9% of variance respectively),
      suggesting that despite the proposed ubiquity of ecological divergence, non
      ecological factors play the dominant role in the evolution of spatial genetic
      divergence.

PMID- 23137143
TI  - The generalizability of psychotherapy efficacy trials in major depressive
      disorder: an analysis of the influence of patient selection in efficacy trials on
      symptom outcome in daily practice.
AB  - BACKGROUND: Treatment guidelines for major depressive disorder (MDD) are based on
      results from randomized clinical trials, among others in psychotherapy efficacy
      trials. However, patients in these trials differ from routine practice patients
      since trials use stringent criteria for patient selection. It is unknown whether
      the exclusion criteria used in psychotherapy efficacy trials (PETs) influence
      symptom outcome in clinical practice. We first explored which exclusion criteria
      are used in PETs. Second, we investigated the influence of commonly used
      exclusion criteria on symptom outcome in routine clinical practice. METHODS: We
      performed an extensive literature search in PubMed, PsycInfo and additional
      databases for PETs for MDD. From these, we identified commonly used exclusion
      criteria. We investigated the influence of exclusion criteria on symptom outcome
      by multivariate regression models in a sample of patients suffering from MDD
      according to the MINIplus from a routine clinical practice setting (n=598). Data
      on routine clinical practice patients were gathered through Routine Outcome
      Monitoring. RESULTS: We selected 20 PETs and identified the following commonly
      used exclusion criteria: 'a baseline severity threshold of HAM-D<=14', 'current
      or past abuse or dependence of alcohol and/or drugs' and 'previous use of
      medication or ECT'. In our routine clinical practice sample of patients suffering
      from MDD (n=598), presence of 'current or past abuse of or dependence on alcohol
      and/or drugs' had no significant influence on outcome.'Meeting a baseline
      severity threshold of HAM-D<=14' and 'previous use of medication or ECT' were
      associated with better outcome, but the explained variance of the models was very
      small (R2=2-11%). CONCLUSIONS: The most consistently used exclusion criteria are
      not a major threat to the generalizability of results found in PETs. However,
      PETs do somewhat improve their results by exclusion of patients with minor
      depression and patients who used antidepressants prior to psychotherapy.

PMID- 23137144
TI  - Isotope pattern deconvolution for peptide mass spectrometry by non-negative least
      squares/least absolute deviation template matching.
AB  - BACKGROUND: The robust identification of isotope patterns originating from
      peptides being analyzed through mass spectrometry (MS) is often significantly
      hampered by noise artifacts and the interference of overlapping patterns arising
      e.g. from post-translational modifications. As the classification of the recorded
      data points into either 'noise' or 'signal' lies at the very root of essentially
      every proteomic application, the quality of the automated processing of mass
      spectra can significantly influence the way the data might be interpreted within
      a given biological context. RESULTS: We propose non-negative least squares/non
      negative least absolute deviation regression to fit a raw spectrum by templates
      imitating isotope patterns. In a carefully designed validation scheme, we show
      that the method exhibits excellent performance in pattern picking. It is
      demonstrated that the method is able to disentangle complicated overlaps of
      patterns. CONCLUSIONS: We find that regularization is not necessary to prevent
      overfitting and that thresholding is an effective and user-friendly way to
      perform feature selection. The proposed method avoids problems inherent in
      regularization-based approaches, comes with a set of well-interpretable
      parameters whose default configuration is shown to generalize well without the
      need for fine-tuning, and is applicable to spectra of different platforms. The R
      package IPPD implements the method and is available from the Bioconductor
      platform (http://bioconductor.fhcrc.org/help/bioc
      views/devel/bioc/html/IPPD.html).

PMID- 23137145
TI  - Differing photo-oxidation mechanisms: electron transfer in TiO2 versus iron-doped
      TiO2.
AB  - Low-level iron doping has been found to alter the photo-oxidation mechanism of
      TiO(2) by efficiently activating molecular oxygen. In the absence of iron, TiO(2)
      either reduces water or stores the electron. Quantitatively, 0.5% Fe-TiO(2) is
      nearly three times as efficient as undoped TiO(2); 0.1% Fe-TiO(2) is twice as
      efficient. It is found that the efficiency boost primarily results from a more
      effective use of the absorbed UV photons. Extension of absorption into the
      visible region due to iron doping increases the efficiency by a factor of only
      1.03 compared with UV-only irradiation. Characterization of these small particles
      reveals that particle size, crystal structure (anatase in all cases), and exposed
      faces are all insensitive to iron doping. Iron modifies the electronic states of
      TiO(2) by introducing an interband state and enhancing population of a newly
      identified state at +1.48 eV that acts as an efficient electron-hole
      recombination site. Activation of molecular oxygen effectively competes with
      electron-hole pair recombination.

PMID- 23137146
TI  - Reflections on clinical applications of yoga in voice therapy with MTD.
AB  - This paper explores the application of modified yoga techniques, as an adjunct to
      voice therapy, by a speech pathologist who is also a yoga teacher. Yoga
      practices, with effects that may be short-term, are not considered a substitute
      for comprehensive and integrated somatic retraining systems (such as the
      Alexander Technique or Feldenkrais ATM). However, when yoga is conducted
      emphasizing kinaesthetic and proprioceptive awareness, the client may achieve an
      'awareness state' that facilitates the learning of vocal remediation techniques
      (for example, by more easily 'tuning in' to the subtle sensations of
      supralaryngeal deconstriction). Core yoga elements and clinical applications are
      identified. The potential benefits and considerations when using yoga as an
      adjunct to the treatment of muscle tension dysphonia (MTD) are explored.

PMID- 23137147
TI  - The PEG-fluorochrome shielding approach for targeted probe design.
AB  - We provide a new approach for fluorescent probe design termed "PEG-fluorochrome
      shielding", where PEGylation enhances quantum yields while blocking troublesome
      interactions between fluorochromes and biomolecules. To demonstrate PEG
      fluorochrome shielding, fluorochrome-bearing peptide probes were synthesized,
      three without PEG and three with a 5 kDa PEG functional group. In vitro, PEG
      blocked the interactions of fluorochrome-labeled peptide probes with each other
      (absorption spectra, self-quenching) and reduced nonspecific interactions with
      cells (by FACS). In vivo, PEG blocked interactions with biomolecules that lead to
      probe retention (by surface fluorescence). Integrin targeting in vivo was
      obtained as the differential uptake of an (111)In-labeled, fluorochrome-shielded,
      integrin-binding RGD probe and a control RAD. Using PEG to block fluorochrome
      mediated interactions, rather than synthesizing de novo fluorochromes, can yield
      new approaches for the design of actively or passively targeted near-infrared
      fluorescent probes.

PMID- 23137149
TI  - Communicating the new pharmacovigilance landscape.

PMID- 23137152
TI  - Comparing tolerability of olanzapine in schizophrenia and affective disorders: a
      meta-analysis.

PMID- 23137151
TI  - Individual NSAIDs and upper gastrointestinal complications: a systematic review
      and meta-analysis of observational studies (the SOS project).
AB  - BACKGROUND: The risk of upper gastrointestinal (GI) complications associated with
      the use of NSAIDs is a serious public health concern. The risk varies between
      individual NSAIDs; however, there is little information on the risk associated
      with some NSAIDs and on the impact of risk factors. These data are necessary to
      evaluate the benefit-risk of individual NSAIDs for clinical and health policy
      decision making. Within the European Community's Seventh Framework Programme, the
      Safety Of non-Steroidal anti-inflammatory drugs (NSAIDs) [SOS] project aims to
      develop decision models for regulatory and clinical use of individual NSAIDs
      according to their GI and cardiovascular safety. OBJECTIVE: The aim of this study
      was to conduct a systematic review and meta-analysis of observational studies to
      provide summary relative risks (RR) of upper GI complications (UGIC) associated
      with the use of individual NSAIDs, including selective cyclooxygenase-2
      inhibitors. METHODS: We used the MEDLINE database to identify cohort and case
      control studies published between 1 January 1980 and 31 May 2011, providing
      adjusted effect estimates for UGIC comparing individual NSAIDs with non-use of
      NSAIDs. We estimated pooled RR and 95% CIs of UGIC for individual NSAIDs overall
      and by dose using fixed- and random-effects methods. Subgroup analyses were
      conducted to evaluate methodological and clinical heterogeneity between studies.
      RESULTS: A total of 2984 articles were identified and 59 were selected for data
      abstraction. After review of the abstracted information, 28 studies met the meta
      analysis inclusion criteria. Pooled RR ranged from 1.43 (95% CI 0.65, 3.15) for
      aceclofenac to 18.45 (95% CI 10.99, 30.97) for azapropazone. RR was less than 2
      for aceclofenac, celecoxib (RR 1.45; 95% CI 1.17, 1.81) and ibuprofen (RR 1.84;
      95% CI 1.54, 2.20); 2 to less than 4 for rofecoxib (RR 2.32; 95% CI 1.89, 2.86),
      sulindac (RR 2.89; 95% CI 1.90, 4.42), diclofenac (RR 3.34; 95% CI 2.79, 3.99),
      meloxicam (RR 3.47; 95% CI 2.19, 5.50), nimesulide (RR 3.83; 95% CI 3.20, 4.60)
      and ketoprofen (RR 3.92; 95% CI 2.70, 5.69); 4-5 for tenoxicam (RR 4.10; 95% CI
      2.16, 7.79), naproxen (RR 4.10; 95% CI 3.22, 5.23), indometacin (RR 4.14; 95% CI
      2.91, 5.90) and diflunisal (RR 4.37; 95% CI 1.07, 17.81); and greater than 5 for
      piroxicam (RR 7.43; 95% CI 5.19, 10.63), ketorolac (RR 11.50; 95% CI 5.56, 23.78)
      and azapropazone. RRs for the use of high daily doses of NSAIDs versus non-use
      were 2-3 times higher than those associated with low daily doses. CONCLUSIONS: We
      confirmed variability in the risk of UGIC among individual NSAIDs as used in
      clinical practice. Factors influencing findings across studies (e.g. definition
      and validation of UGIC, exposure assessment, analysis of new vs prevalent users)
      and the scarce data on the effect of dose and duration of use of NSAIDs and on
      concurrent use of other medications need to be addressed in future studies,
      including SOS.

PMID- 23137150
TI  - Current challenges and controversies in drug-induced liver injury.
AB  - Current key challenges and controversies encountered in the identification of
      potentially hepatotoxic drugs and the assessment of drug-induced liver injury
      (DILI) are covered in this article. There is substantial debate over the
      classification of DILI itself, including the definition and validity of terms
      such as 'intrinsic' and 'idiosyncratic'. So-called idiosyncratic DILI is
      typically rare and requires one or more susceptibility factors in individuals.
      Consequently, it has been difficult to reproduce in animal models, which has
      limited the understanding of its underlying mechanisms despite numerous
      hypotheses. Advances in predictive models would also help to enable preclinical
      elimination of drug candidates and development of novel biomarkers. A small
      number of liver laboratory tests have been routinely used to help identify DILI,
      but their interpretation can be limited and confounded by multiple factors.
      Improved preclinical and clinical biomarkers are therefore needed to accurately
      detect early signals of liver injury, distinguish drug hepatotoxicity from other
      forms of liver injury, and differentiate mild from clinically important liver
      injury. A range of potentially useful biomarkers are emerging, although so far
      most have only been used preclinically, with only a few validated and used in the
      clinic for specific circumstances. Advances in the development of genomic
      biomarkers will improve the prediction and detection of hepatic injury in future.
      Establishing a definitive clinical diagnosis of DILI can be difficult, since it
      is based on circumstantial evidence by excluding other aetiologies and, when
      possible, identifying a drug-specific signature. DILI signals based on standard
      liver test abnormalities may be affected by underlying diseases such as hepatitis
      B and C, HIV and cancer, as well as the concomitant use of hepatotoxic drugs to
      treat some of these conditions. Therefore, a modified approach to DILI assessment
      is justified in these special populations and a suggested framework is presented
      that takes into account underlying disease when evaluating DILI signals in
      individuals. Detection of idiosyncratic DILI should, in some respects, be easier
      in the postmarketing setting compared with the clinical development programme,
      since there is a much larger and more varied patient population exposure over
      longer timeframes. However, postmarketing safety surveillance is currently
      limited by the quantity and quality of information available to make an accurate
      diagnosis, the lack of a control group and the rarity of cases. The pooling of
      multiple healthcare databases, which could potentially contain different types of
      patient data, is advised to address some of these deficiencies.

PMID- 23137154
TI  - Olanzapine in schizophrenia and affective disorders.

PMID- 23137156
TI  - Neuropsychiatric adverse events and oseltamivir for prophylaxis.

PMID- 23137159
TI  - Signaling pathways of PAX2 and its role in renal interstitial fibrosis and
      glomerulosclerosis.
AB  - PAX2, a nuclear transcription factor in renal development, is strongly expressed
      during kidney development and plays an important role in kidney development,
      differentiation, and renal cell proliferation. PAX2 is expressed in epithelial
      cells of fetal kidneys and its expression is up-regulated in certain pathologic
      conditions. However, the transcription activation of PAX2 and its signaling
      pathways are complicated. Recent discoveries find that the PAX2 gene is pivotal
      in kidney development and it is implicated in the pathogenesis of renal
      interstitial fibrosis (RIF) and glomerulosclerosis (GS). Here, I comprehensively
      reviewed the signal transduction pathways of PAX2 and its role in the
      pathogenesis of RIF and GS.

PMID- 23137160
TI  - Safety and efficacy of subcutaneous hepatitis B immunoglobulin after liver
      transplantation: an open single-arm prospective study.
AB  - Life-long hepatitis B immunoglobulin (HBIG) administration is a main component of
      prophylactic strategy to prevent hepatitis B virus (HBV) reinfection after liver
      transplantation (LT). Long-term effects of HBIG treatment are known only for
      intravenous (IV) and intramuscular formulations. To evaluate safety and efficacy
      of self-administered SC HBIG, 135 LT patients receiving a 48-week treatment were
      analyzed. The dose of HBIG was 500 IU or 1000 IU if body weight was <75 kg or
      >=75 kg, respectively. Patients were switched from the monthly IV HBIG treatment
      to weekly SC HBIG 2-3 weeks after the last IV dosage. All patients were able to
      SC self-injection after a single training. The treatment was effective in
      maintaining trough anti-HBs levels >100 IU/L. No severe drug-related side effects
      occurred. Fifteen injection-site small hematomas and four cases of mild itch
      occurred. At the end of the study, anti-HBs median titer was 232 IU/L (115-566
      IU/L) and 97.8% of patients had an anti-HBs level >150 IU/L. Due to high mean
      level of anti-HBs titers observed during this study, individualized treatment
      schedules should be further investigated. In conclusion, SC HBIG for long-term
      prophylaxis of post-LT HBV reinfection resulted safe, well accepted, and
      effective in maintaining adequate anti-HBs levels.

PMID- 23137161
TI  - Infant growth patterns of the mandible in modern humans: a closer exploration of
      the developmental interactions between the symphyseal bone, the teeth, and the
      suprahyoid and tongue muscle insertion sites.
AB  - The ontogenetic development of the mental region still poses a number of
      unresolved questions in human growth, development and phylogeny. In our study we
      examine the hypotheses of DuBrul & Sicher (1954) (The Adaptive Chin. Springfield,
      IL: Charles) and Enlow (1990) (Facial Growth, 3rd edn. Philadelphia, PA:
      Saunders) to explain the presence of a prominent mental region in anatomically
      modern humans. In particular, we test whether the prominence of the mental region
      and the positioning of the teeth are both correlated with the developmental
      relocation of the tongue and the suprahyoid muscles inserting at the lingual side
      of the symphysis. Furthermore, we test whether the development of the mental
      region is associated with the development of the back of the vocal tract. Using
      geometric morphometric methods, we measured the 3D mandibular and tooth surfaces
      in a cross-sectional sample of 36 CT-scanned living humans, incorporating the
      positions of the tongue and the geniohyoid and digastric muscle insertions. The
      specimens' ages range from birth to the complete emergence of the deciduous
      dentition. We used multivariate regression and two-block partial least squares
      (PLS) analysis to study the covariation among the mental region, the muscle
      insertions, and the teeth both across and within age stages. In order to confirm
      our results from the 3D cross-sectional sample, and to relate them to facial
      growth and the position of the cervical column and the hyoid bone, we used 46
      lateral radiographs of eight children from the longitudinal Denver Growth Study.
      The 3D analysis demonstrates that the lingual side of the lower border of the
      symphysis develops downwards and forwards. These shape changes are significantly
      correlated with the relocation of muscle insertion sites and also with the
      vertical reorientation of the anterior teeth prior to emergence. The 2D analysis
      confirms the idea that as the mental region prominence develops, the space of the
      laryngopharynx becomes restricted due to upper mid-face retraction and the
      acquisition of upright body posture. In agreement with the hypotheses of DuBrul &
      Sicher (1954) and Enlow (1990), our results suggest that the presence of a
      prominent mental region responds to the space restriction at the back of the
      vocal tract, and to the packaging of the tongue and suprahyoid muscles in order
      to preserve the functionality of the laryngopharynx during respiration, feeding
      and speech.

PMID- 23137162
TI  - Dronedarone: is it time to turn it down?

PMID- 23137163
TI  - Phosphatidylethanolamine-lactose permease interaction: a comparative study based
      on FRET.
AB  - In this work we have investigated the selectivity of lactose permease (LacY) of
      Escherichia coli (E. coli) for its surrounding phospholipids when reconstituted
      in binary mixtures of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine
      (POPE), 1,2-Palmitoyl-sn-glycero-3-phosphoethanolamine (DPPE), or 1,2-dioleoyl-sn
      glycero-3-phosphoethanolamine (DOPE) with 1-palmitoyl-2-oleoyl-sn-glycero-3
      (phospho-rac-(1-glycerol)) (POPG). Forster resonance energy transfer (FRET)
      measurements have been performed to investigate the selectivity between a single
      tryptophan mutant of LacY used as donor (D), and two analogues of POPE and POPG
      labeled with pyrene in the acyl chains (Pyr-PE and Pyr-PG) used as acceptors. As
      a difference from previous works, now the donor has been single-W151/C154G/D68C
      LacY. It has been reported that the replacement of the aspartic acid in position
      68 by cysteine inhibits active transport in LacY. The objectives of this work
      were to elucidate the phospholipid composition of the annular region of this
      mutant and to determine whether the mutation performed, D68C, induced changes in
      the protein-lipid selectivity. FRET efficiencies for Pyr-PE were always higher
      than for Pyr-PG. The values of the probability of each site in the annular ring
      being occupied by a label (MU) were similar at the studied temperatures (24 
      degrees C and 37  degrees C), suggesting that the lipid environment is not
      significantly affected when increasing the temperature. By comparing the results
      with those obtained for single-W151/C154G LacY, we observe that the mutation in
      the 68 residue indeed changes the selectivity of the protein for the
      phospholipids. This might be probably due to a change in the conformational
      dynamics of LacY.

PMID- 23137164
TI  - Positive C4d immunostaining of placental villous syncytiotrophoblasts supports
      host-versus-graft rejection in villitis of unknown etiology.
AB  - ABSTRACT   Chronic villitis of unknown etiology (VUE) occurs in 5% of placentas
      submitted to pathology and is characterized by lymphohistiocytic infiltration of
      chorionic villi. VUE is associated with fetal growth restriction, preterm birth,
      and recurrent pregnancy loss. Accumulating evidence indicates that VUE may
      represent a host-versus-graft reaction analogous to transplant rejection.
      Pathologists routinely screen for antibody-mediated rejection in transplant
      biopsies by immunostaining for C4d, which highlights the recognition of donor
      cells by the host immune system. Since the hemochorial placenta is bathed in
      maternal blood, we hypothesized that cases of VUE may show C4d deposition onto
      villous syncytiotrophoblasts (STB). Chronic villitis was diagnosed in 82 of 1986
      (4%) singleton placentas submitted to our department from 2007 through 2011.
      Forty randomly selected cases were gestational age-matched with 40 negative
      controls. Patient charts were reviewed and representative placental sections were
      immunostained for C4d. A positive C4d result was defined as circumferential
      immunostaining of the STB around at least one villous, or strong staining of
      fetal endothelial cells in the chorionic plate or stem villi. Our data indicate
      that VUE usually occurs in the 3rd trimester (37 +/- 0.5 weeks) and is associated
      with significantly reduced placental weight (P  =  0.006). Positive C4d staining
      of STB was more common in VUE (35/40, 88%) compared with negative controls (2/40,
      5%) (P < 0.0001). It was also more common in multiparous (35/66, 53%) than
      primiparous (2/14, 14%) women (P < 0.01). Although the precise mechanism remains
      to be determined, our data support the hypothesis that VUE may represent host
      versus-graft rejection by the mother.

PMID- 23137165
TI  - Tanshinone IIA inhibits metastasis after palliative resection of hepatocellular
      carcinoma and prolongs survival in part via vascular normalization.
AB  - BACKGROUND: Promotion of endothelial normalization restores tumor oxygenation and
      obstructs tumor cells invasion, intravasation, and metastasis. We therefore
      investigated whether a vasoactive drug, tanshinone IIA, could inhibit metastasis
      by inducing vascular normalization after palliative resection (PR) of
      hepatocellular carcinoma (HCC). METHODS: A liver orthotopic double-tumor
      xenograft model in nude mouse was established by implantation of HCCLM3 (high
      metastatic potential) and HepG2 tumor cells. After removal of one tumor by PR,
      the effects of tanshinone IIA administration on metastasis, tumor
      vascularization, and survival were evaluated. Tube formation was examined in
      mouse tumor-derived endothelial cells (TECs) treated with tanshinone IIA.
      RESULTS: PR significantly accelerated residual hepatoma metastases. Tanshinone
      IIA did not inhibit growth of single-xenotransplanted tumors, but it did reduce
      the occurrence of metastases. Moreover, it inhibited PR-enhanced metastases and,
      more importantly, prolonged host survival. Tanshinone IIA alleviated residual
      tumor hypoxia and suppressed epithelial-mesenchymal transition (EMT) in vivo;
      however, it did not downregulate hypoxia-inducible factor 1alpha (HIF-1alpha) or
      reverse EMT of tumor cells under hypoxic conditions in vitro. Tanshinone IIA
      directly strengthened tube formation of TECs, associated with vascular
      endothelial cell growth factor receptor 1/platelet derived growth factor receptor
      (VEGFR1/PDGFR) upregulation. Although the microvessel density (MVD) of residual
      tumor tissue increased after PR, the microvessel integrity (MVI) was still low.
      While tanshinone IIA did not inhibit MVD, it did dramatically increase MVI,
      leading to vascular normalization. CONCLUSIONS: Our results demonstrate that
      tanshinone IIA can inhibit the enhanced HCC metastasis associated with PR.
      Inhibition results from promoting VEGFR1/PDGFR-related vascular normalization.
      This application demonstrates the potential clinical benefit of preventing
      postsurgical recurrence.

PMID- 23137166
TI  - Treatment with finasteride and prostate cancer survival.
AB  - OBJECTIVE: This study compared survival after diagnosis of prostate cancer (PC)
      in men previously treated with finasteride, in men previously treated with alpha
      adrenoceptor antagonists, in men treated with both, and in men who had received
      neither type of medication. MATERIAL AND METHODS: In total, 3791 men diagnosed
      with PC in northern Denmark were identified. The region's prescription database
      was used to identify all men prescribed finasteride and alpha-adrenoceptor
      antagonists and those who had received neither medication during the period 1989
      2001. Among men with a diagnosis of PC, overall survival and disease-specific
      survival were assessed after diagnosis using Cox proportional hazards regression.
      The risk of being diagnosed with non-localized PC was estimated using conditional
      logistic regression. RESULTS: The adjusted hazard ratio (HR) for PC death and
      overall death after treatment with finasteride was 0.93 [95% confidence interval
      (CI) 0.76-1.14] and 0.92 (95% CI 0.77-1.10), respectively. Treatment with alpha
      adrenoceptor antagonists was associated with a reduced risk of PC death and
      overall death (HR 0.78, 95% CI 0.67-0.90, and 0.82, 95% CI 0.73-0.93,
      respectively. The risk of being diagnosed with non-localized PC was increased for
      men taking finasteride (odds ratio 1.14, 95% CI 1.01-1.29) per 100 defined daily
      doses. CONCLUSIONS: Treatment with finasteride prior to a diagnosis of PC did not
      affect PC-specific survival, but increased the risk of being diagnosed with non
      localized disease. Treatment with alpha-adrenoceptor antagonists was associated
      with better cause-specific survival and lower risk of non-localized disease.

PMID- 23137167
TI  - Zinc therapy improves deleterious effects of chronic copper administration on
      mice testes: histopathological evaluation.
AB  - This study was set to investigate whether the adverse effects of long-term copper
      (Cu) consumption on testicular tissue could be prevented by zinc (Zn)
      administration. Forty-five mature male mice were randomly divided into one
      control and two treatment groups. The first treatment group received copper
      sulphate (Cu experimental group). The second treatment group was given combined
      treatment of copper sulphate and zinc sulphate (ZC experimental group). Control
      animals received normal saline using the same volume. Five mice from each group
      were sacrificed on day 14, 28 and 56 from the beginning of treatments. Left
      testes were removed for histopathological and histomorphometrical evaluations.
      Morphometrically, the diameter of seminiferous tubules and Sertoli cell nuclei,
      epithelial height, meiotic index and the percentage of spermatogenesis in Cu
      groups showed significant decrease compared to those of the control groups (P <
      0.05). A partial improvement was seen in the percentage of spermatogenesis and
      meiotic index (P < 0.05) in ZC groups, whereas a complete recovery was observed
      in the rest of parameters in ZC group after 56 days compared to the control group
      (P > 0.05). Results showed that long-term administration of Cu leads to
      histological impairments of testis and zinc supplementation might offset these
      damaging effects.

PMID- 23137168
TI  - Vaginal self-sampling is an adequate means of screening HR-HPV types in women not
      participating in regular cervical cancer screening.
AB  - In France, about 40% of women aged 25-65 years do not participate in regular
      screening and thus are at high risk (HR) of cervical cancer. Human papillomavirus
      (HPV) vaginal self-sampling is a valuable alternative in this population. This
      study aimed to assess the prevalence of HR and LR (low-risk) HPV infection in
      3767 women aged >35 years from mid-socioeconomic backgrounds who carried out HPV
      vaginal self-sampling at home. HPV vaginal self-sampling was better accepted than
      the Pap-test in women aged 35-69 years who were previously non-responders to
      individual invitation. From the 933 self-collected swabs studied (24.7%), 62 were
      HPV-infected (6.6%), and 73 HPV types were found. HPV 16 was the most frequently
      found (43.5%), followed by 53 (23.2%), 18 (12.3%), 66 (12.3%), 31 (6.8%), 33
      (5.4%) and 58 (2.7%). Ten women (16.2%) were infected by multiple HR-HPV types.
      Median HPV 16 load was 104.000 copies/10(6) cells and median HPV 18 load was 833
      copies/10(6) cells. Six women (9.3%) harboured LR-HPV types. The 12-month follow
      up of 43 HR-HPV positive women (69.3%) revealed CIN2-3 lesions in three women
      (6.9%), all HPV 16 infected, and harbouring an HPV 16 load >5 log(10)
      copies/10(6) cells. Women harbouring HR-HPV types other than HPV 16/18 were older
      than women harbouring HPV 16/18 types (55 years vs. 46.9 years, p 0.0008). The
      high frequency of HR-HPV types in women >50 years deserves further investigation
      to elucidate the mechanism involved (re-infection or reactivation).

PMID- 23137169
TI  - Preliminary validation of the Defense and Veterans Pain Rating Scale (DVPRS) in a
      military population.
AB  - BACKGROUND: The Army Surgeon General released the Pain Management Task Force
      final report in May 2010. Among military providers, concerns were raised that the
      standard numeric rating scale (NRS) for pain was inconsistently administered and
      of questionable clinical value. In response, the Defense and Veterans Pain Rating
      Scale (DVPRS) was developed. METHODS: The instrument design integrates pain
      rating scale features to improve interpretability of incremental pain intensity
      levels, and to improve communication and documentation across all transitions of
      care. A convenience sample of 350 inpatient and outpatient active duty or retired
      military service members participated in the study at Walter Reed Army Medical
      Center. Participants completed the five-item DVPRS-one pain intensity NRS with
      and without word descriptors presented in random order and four supplemental
      items measuring general activity, sleep, mood, and level of stress and the Brief
      Pain Inventory seven interference items. Using systematic sampling, a random
      sample was selected for a word descriptor validation procedure matching word
      phases to corresponding pain intensity on the NRS. RESULTS: Parallel forms
      reliability and concurrent validity testing demonstrated a robust correlation.
      When the DVPRS was presented with the word descriptors first, the correlation
      between the two ratings was slightly higher, r = 0.929 (N = 171; P < 0.001), than
      ordering first without the descriptors, r = 0.882 (N = 177; P < 0.001).
      Intraclass correlation coefficient was 0.943 showing excellent alignment of word
      descriptors by respondents (N = 42), matching them correctly with pain level.
      CONCLUSIONS: The DVPRS tool demonstrated acceptable psychometric properties in a
      military population.

PMID- 23137170
TI  - Dual fluorescent labelling of the human malaria parasite Plasmodium falciparum
      for the analysis of the ABC type transporter pfmdr2.
AB  - BACKGROUND: The study of the Plasmodium falciparum heavy metal transporter gene
      pfmdr2 employed radioactive labelled heavy metal. As the use of radioactive
      isotopes shrank considerably during the last few years, resulting in the
      cessation of the production of some isotopes, amongst them Cadmium109 which was
      used for that purpose, a different approach had to be developed. Herein, a dual
      fluorescent labelling of heavy metals accumulation in the P. falciparum parasite
      is proposed as an alternative to the use of radioactive labelled heavy metals.
      METHODS: Plasmodium falciparum Cd resistant and sensitive strains at the
      trophozoite stage were used in this study. The cells were cultured at different
      CdCl2 concentrations and for different time periods followed by staining of the
      infected red blood cells with Fluo-3/AM for Cd detection and Hoechst 33342 for
      parasite DNA labelling. The fluorescent analysis was done by flow cytometry and
      confocal microscopy. RESULTS: The results show that the sensitive strain has a
      higher Fluo-3/AM fluorescence in a Cd concentration and time dependent manner,
      whereas in the resistant strain Fluo-3/AM fluorescence levels were negligible and
      increased only at high concentrations of Cd and at long incubation periods, but
      to a much lesser extent than the sensitive strain. No Cd uptake is observed in
      uninfected red blood cells populations originating from cultures infected with
      either sensitive or resistant strain. In addition, confocal microscopy overlay of
      Fluo-3/AM and Hoechst staining shows that the Cd metal accumulates in the
      parasite itself. CONCLUSIONS: The dual fluorescent labelling is a valid method
      for detecting heavy metal accumulation in P. falciparum. Furthermore, in contrast
      to the use of radioactive labelled heavy metal, the fluorescent labelling enables
      us to differentiate between the different populations existing in a P. falciparum
      infected red blood cells cultures and thus actually study a phenomenon at the
      level of a single cell.

PMID- 23137171
TI  - Disability and schizophrenia: a systematic review of experienced psychosocial
      difficulties.
AB  - BACKGROUND: Schizophrenia is a significantly disabling disease that affects all
      major areas of life. There is a lack of comprehensive synthesis of research
      findings on the full extent of psychosocial difficulties (PSDs) experienced by
      people living with schizophrenia. This paper provides a systematic review of the
      literature concerning PSDs and their associated factors in schizophrenia. PSDs
      were conceptualized in accordance with the International Classification of
      Functioning, Disability and Health (ICF) as disabilities, in particular
      impairments of mental functions, activity limitations and participation
      restrictions. METHODS: An electronic search using MEDLINE and PsychINFO plus a
      manual search of the literature was performed for qualitative and longitudinal
      studies published in English between 2005 and 2010 that examined PSDs in persons
      with schizophrenia. The ICF was used as a conceptual framework. RESULTS: A total
      of 104 papers were included. The most frequent PSDs addressed in the literature
      were not specific ones, directly linkable to the ICF categories of mental
      functions, activity limitations or participation restrictions, but broad areas of
      psychosocial functioning, such as psychopathological symptoms (53% of papers) or
      global disability and functioning (37%). Among mental functions, the most
      extensively studied were cognitive functions (27%) and emotional functions (27%).
      Within the domain of activities and participation, the most widely investigated
      were difficulties in relationships with others (31%) and employment (20%). Of the
      factors associated with the intensity or course of PSDs, the most commonly
      identified were treatment modalities (56%), psychopathological symptoms (26%),
      and socio-demographic variables (24%). Medication tended to improve the most
      relevant PSD, but at the same time was the only consistently reported determinant
      of onset of PSDs (emerging as unwanted side-effects). CONCLUSIONS: The present
      review illustrates the remarkably broad scope and diversity of psychosocial areas
      affected in schizophrenia and shows how these areas are interconnected and how
      they interact with contextual factors. The need for a shift in focus of
      schizophrenia research is suggested--from an excessive reliance on global
      measures of psychopathology and disability for defining outcomes to the creation
      of profiles of specific PSDs that have a more direct bearing on the disabling
      experience and real-world functioning of patients and can serve to guide
      interventions and monitoring over time.

PMID- 23137172
TI  - Phase behavior of dense colloidal binary monolayers.
AB  - In this work, we study how structures develop on 2D dense binary colloidal
      monolayers as a function of the relative concentration of small/large particles.
      Translational and orientational distribution functions have been used to monitor
      the continuous phase transition through a detailed characterization of the global
      and local order. We have observed how a gradual enhancement in the number of
      particles of different sizes leads to a continuous vitrification process and how
      homogeneous binary glasses form in equimolar mixtures. Also, we have performed a
      simple calculation that relates the structures found to the pair dipolar
      potential, allowing the forecast of local structures in other arbitrary binary
      mixtures. Finally, we have corroborated the goodness of the binary systems as a
      glass-forming model by comparing the established scenario with the structural
      features found in partially aggregated monolayers.

PMID- 23137173
TI  - Unrelated facultative endosymbionts protect aphids against a fungal pathogen.
AB  - The importance of microbial facultative endosymbionts to insects is increasingly
      being recognized, but our understanding of how the fitness effects of infection
      are distributed across symbiont taxa is limited. In the pea aphid, some of the
      seven known species of facultative symbionts influence their host's resistance to
      natural enemies, including parasitoid wasps and a pathogenic fungus. Here we show
      that protection against this entomopathogen, Pandora neoaphidis, can be conferred
      by strains of four distantly related symbionts (in the genera Regiella,
      Rickettsia, Rickettsiella and Spiroplasma). They reduce mortality and also
      decrease fungal sporulation on dead aphids which may help protect nearby
      genetically identical insects. Pea aphids thus obtain protection from natural
      enemies through association with a wider range of microbial associates than has
      previously been thought. Providing resistance against natural enemies appears to
      be a particularly common way for facultative endosymbionts to increase in
      frequency within host populations.

PMID- 23137174
TI  - Macrophage migration inhibitory factor (MIF) enhances palmitic acid- and glucose
      induced murine beta cell dysfunction and destruction in vitro.
AB  - Although several reports suggest a potentially deleterious role of macrophage
      migration inhibitory factor (MIF) in type 2 diabetes (T2D) pathology, it is still
      unclear how this pro-inflammatory cytokine acts on pancreatic beta cells. The aim
      of the present study was to evaluate MIF effects on murine beta cells in the in
      vitro settings mimicking T2D-associated conditions. Results indicate that
      recombinant MIF further increased apoptosis of pancreatic islets or MIN6 cells
      upon exposure to palmitic acid or glucose. This was accompanied by upregulation
      of several pro-apoptotic molecules. Furthermore, MIF potentiated nutrient-induced
      islet cell dysfunction, as revealed by lower glucose oxidation rate, ATP content,
      and depolarized mitochondrial membrane. The final outcome was potentiation of
      mitochondrial apoptotic pathway. The observed upregulation of nutrient-induced
      islet cell dysfunction and apoptosis by MIF implicates that silencing MIF may be
      beneficial for maintaining integrity of endocrine pancreas in obesity-associated
      T2D.

PMID- 23137175
TI  - [An approach to the legal and ethical problem of surrogate motherhood].
AB  - Surrogate motherhood is an issue which currently gives rise to considerable
      complexity. Some consider that it is a justifiable practice which should be
      permitted by law. However, western legal systems have traditionally understood
      that whereas objects can be traded freely, persons, including the human body, its
      organs and most essential functions, cannot be the object of commerce. This means
      that the freedom of the individual to make contracts for mutual benefit is
      limited. Regarding the child, legalization of surrogate motherhood means
      converting the parent-child relationship into a commercial relationship, since in
      the last instance this would depend on a financial transaction. Moreover,
      experience has shown that the child is left in a very vulnerable position, since
      his or her situation depends on the clauses set forth in the contract, which in
      no sense guarantees that his or her interests and rights will be protected. For
      all these reasons, we must conclude that the wish on the part of infertile
      couples should be taken seriously by society. However, not all desires that
      adults have should be regarded as rights, particularly if this is detrimental to
      the dignity and rights of other subjects involved, particularly those of
      vulnerable women and their children.

PMID- 23137177
TI  - General insights into structural evolution of layered double hydroxide:
      underlying aspects in topochemical transformation from brucite to layered double
      hydroxide.
AB  - The topochemical transformation from transition-metal brucite hydroxide (Co(1
      x)Fe(x)(OH)(2), Co(OH)(2), Co(1-x)Ni(x)(OH)(2)) to corresponding (Co(2+)-(Co(3+))
      Fe(3+), Co(2+)-(Ni(2+))-Co(3+)) LDH under oxidizing halogen agents (iodine,
      bromine) exhibits different staging phenomena depending on the metallic
      composition/ratio in starting brucite. A plausible charge hopping mechanism based
      on valence interchange between redoxable charge center (Fe(3+)/Co(3+)) and
      neighboring divalent sites in the host sheet is proposed to understand the
      restoration of electron donor sites at the interface between brucite crystallites
      and halogen agents, which ensures a continual oxidative reaction, and a staged
      intercalation/diffusion of in situ reduced halide anions into the interlayer
      gallery commensurate with the host charge propagation. The discussion on the
      correlation between staging product and metallic composition/ratio offers a
      general perspective and new insights into M(2+)/M(3+) ratio and cation ordering,
      host layer charge, and phase evolution in LDH structure.

PMID- 23137178
TI  - Adaptive evolution of the chrysanthemyl diphosphate synthase gene involved in
      irregular monoterpene metabolism.
AB  - BACKGROUND: Chrysanthemyl diphosphate synthase (CDS) is a key enzyme in
      biosynthetic pathways producing pyrethrins and irregular monoterpenes. These
      compounds are confined to plants of the tribe Anthemideae of the Asteraceae, and
      play an important role in defending the plants against herbivorous insects. It
      has been proposed that the CDS genes arose from duplication of the farnesyl
      diphosphate synthase (FDS) gene and have different function from FDSs. However,
      the duplication time toward the origin of CDS and the evolutionary force behind
      the functional divergence of the CDS gene are still unknown. RESULTS: Two
      duplication events were detected in the evolutionary history of the FDS gene
      family in the Asteraceae, and the second duplication led to the origin of CDS.
      CDS occurred after the divergence of the tribe Mutisieae from other tribes of
      Asteraceae but before the birth of the Anthemideae tribe. After its origin, CDS
      accumulated four mutations in sites homologous to the substrate-binding and
      catalysis sites of FDS. Of these, two sites were involved in the binding of the
      nucleophilic substrate isopentenyl diphosphate in FDS. Maximum likelihood
      analyses showed that some sites in CDS were under positive selection and were
      scattered throughout primary sequences, whereas in the three-dimensional
      structure model they clustered in the large central cavity. CONCLUSION: Positive
      selection associated with gene duplication played a major role in the evolution
      of CDS.

PMID- 23137179
TI  - Mechanism of [Ca2+]i rise induced by angiotensin 1-7 in MDCK renal tubular cells.
AB  - The effect of angiotensin 1-7 (Ang 1-7) on cytosolic Ca(2+) concentrations
      ([Ca(2+)](i)) in MDCK renal tubular cells was explored. The Ca(2+)-sensitive
      fluorescent dye fura-2 was applied to measure [Ca(2+)](i). Ang 1-7 at
      concentrations of 10-50 uM induced a [Ca(2+)](i) rise in a concentration
      dependent manner. The response was reduced partly by removing Ca(2+). Ang 1-7
      evoked store operated Ca(2+) entry that was inhibited by La(3+) and aristolochic
      acid. In the absence of extracellular Ca(2+), incubation with the endoplasmic
      reticulum Ca(2+) pump inhibitor thapsigargin prevented Ang 1-7 from releasing
      more Ca(2+). Inhibition of phospholipase C with U73122 abolished Ang 1-7-induced
      [Ca(2+)](i) rise. Ang 1-7-induced [Ca(2+)](i) rise was abolished by the
      angiotensin type 1 receptor antagonist losartan, but was not affected by the
      angiotensin type 2 receptor antagonist PD 123,319. In sum, in MDCK cells, Ang 1-7
      stimulated angiotensin type 1 receptors leading to a [Ca(2+)](i) rise that was
      composed of phospholipase C-dependent Ca(2+) release from the endoplasmic
      reticulum and Ca(2+) entry via phospholipase A2-sensitive store-operated Ca(2+)
      channels.

PMID- 23137180
TI  - Polyomavirus BK replication in de novo kidney transplant patients receiving
      tacrolimus or cyclosporine: a prospective, randomized, multicenter study.
AB  - Polyomavirus BK (BKV)-associated nephropathy causes premature kidney transplant
      (KT) failure. BKV viruria and viremia are biomarkers of disease progression, but
      associated risk factors are controversial. A total of 682 KT patients receiving
      basiliximab, mycophenolic acid (MPA), corticosteroids were randomized 1:1 to
      cyclosporine (CsA) or tacrolimus (Tac). Risk factors were analyzed in 629 (92.2%)
      patients having at least 2 BKV measurements until month 12 posttransplant.
      Univariate analysis associated CsA-MPA with lower rates of viremia than Tac-MPA
      at month 6 (10.6% vs. 16.3%, p = 0.048) and 12 (4.8% vs. 12.1%, p = 0.004) and
      lower plasma BKV loads at month 12 (3.9 vs. 5.1 log(10) copies/mL; p = 0.028). In
      multivariate models, CsA-MPA remained associated with less viremia than Tac-MPA
      at month 6 (OR 0.60; 95% CI 0.36-0.99) and month 12 (OR 0.33; 95% CI 0.16-0.68).
      Viremia at month 6 was also independently associated with higher steroid exposure
      until month 3 (OR 1.19 per 1 g), and with male gender (OR 2.49) and recipient age
      (OR 1.14 per 10 years) at month 12. The data suggest a dynamic risk factor
      evolution of BKV viremia consisting of higher corticosteroids until month 3, Tac
      MPA compared to CsA-MPA at month 6 and Tac-MPA, older age, male gender at month
      12 posttransplant.

PMID- 23137181
TI  - Pilot study of high-performance air filtration for classroom applications.
AB  - A study was conducted to investigate the effectiveness of three air purification
      systems in reducing the exposure of children to air contaminants inside nine
      classrooms of three Southern California schools. Continuous and integrated
      measurements were conducted to monitor the indoor and outdoor concentrations of
      ultrafine particles (UFPs), fine and coarse particulate matter (PM2.5 and PM10 ,
      respectively), black carbon (BC), and volatile organic compounds. An heating,
      ventilating, and air conditioning (HVAC)-based high-performance panel filter (HP
      PF), a register-based air purifier (RS), and a stand-alone air cleaning system
      (SA) were tested alone and in different combinations for their ability to remove
      the monitored pollutants. The combination of a RS and a HP-PF was the most
      effective solution for lowering the indoor concentrations of BC, UFPs, and PM2.5
      , with study average reductions between 87% and 96%. When using the HP-PF alone,
      reductions close to 90% were also achieved. In all cases, air quality conditions
      were improved substantially with respect to the corresponding baseline
      (preexisting) conditions. Data on the performance of the gas-absorbing media
      included in the RS and SA unit were inconclusive, and their effectiveness,
      lifetime, costs, and benefits must be further assessed before conclusions and
      recommendations can be made. PRACTICAL IMPLICATIONS: The installation of
      effective air filtration devices in classrooms may be an important mitigation
      measure to help reduce the exposure of school children to indoor pollutants of
      outdoor origin including ultrafine particles and diesel particulate matter,
      especially at schools located near highly trafficked freeways, refineries, and
      other important sources of air toxics.

PMID- 23137182
TI  - Saxagliptin  overview: special focus on safety and adverse effects.
AB  - INTRODUCTION: Saxagliptin (see drug summary box) is a glucose-lowering agent that
      belongs to the class of Dipeptidylpeptidase-4 (DDP-4) inhibitors used in the
      treatment of T2DM. Clinical efficacy of saxagliptin as single agent as well as in
      combination with other medications used for the treatment of T2DM has been well
      established in several randomized trials. Treatment with saxagliptin is
      effective, generally safe and well tolerated, apart from a small increase in the
      incidence of infections such as nasopharyngitis. Its use is not associated with
      increase risk of hypoglycemia and it is weight neutral. Saxagliptin can be used
      safely in renal failure (with dose adjustment) and in hepatic impairment. When
      saxagliptin is used in combination with a strong inhibitor of CYP3A4/A5,
      reduction in the daily dosage is recommended. AREAS COVERED: This paper briefly
      discusses efficacy and pharmacokinetics of saxagliptin. The paper highlights in
      detail saxagliptin-associated adverse effects, drug interactions, its use in
      patients with renal and hepatic disease and long-term safety concerns. EXPERT
      OPINION: Saxagliptin has comparable efficacy with other DPP-4 inhibitors. It is
      generally safe and well tolerated; however, it requires dose adjustment in renal
      disease as well as when used with drugs that are strong inhibitor or inducer of
      CYP3A4/A5 isoforms. Future safety questions regarding immune system and
      development of cancer still remain to be completely answered.

PMID- 23137183
TI  - In vitro inhibition of angiogenesis by hydroalcoholic extract of oak (Quercus
      infectoria) acorn shell via suppressing VEGF, MMP-2, and MMP-9 secretion.
AB  - CONTEXT: Angiogenesis is an essential factor for cancer progression. Although
      more attention is paid in angiogenesis on its role in cancer biology, many other
      non-neoplastic diseases are also angiogenic-dependent. Recently, there is
      motivation to control cancer via inhibition of angiogenesis. OBJECTIVE: Quercus
      infectoria Olivier var (Fagaceae) (oak) is a plant whose different parts, such as
      its fruit shell, have been used extensively as a traditional drug in the west
      part of Iran. Although some biological properties of oak are determined, its
      effects on angiogenesis are unclear. So, we investigated the antiangiogenic
      effects of oak acorn shell. MATERIALS AND METHODS: Fresh oak acorns were
      collected, and after authentication; hydroalcoholic extract of acorn shells (5,
      10, 20, 30, 40, 60, 80, and 100 MUg/ml) was used for evaluation of its
      cytotoxicity, antiproliferative, and antiangiogenic effects in vitro. Also,
      effects of the extract on vascular endothelial growth factor (VEGF), matrix
      metalloproteinase-2 (MMP-2) and MMP-9 secretion were assayed using enzyme-linked
      immunosorbent assay (ELISA) and gelatin zymography. RESULTS: Treatment with
      hydroalcoholic extract in eight doses resulted in a significant decrease of
      endothelial cell proliferation and angiogenesis with an IC50 value of ~20 MUg/ml,
      without any toxic effect. At 40 MUg/ml, the extract inhibited MMP-9 activity;
      however, a dose-dependent reduction (60-80 ug/ml) in MMP-2 activity was seen.
      VEGF secretion was decreased with increase in the concentration of the extract
      from 5 to 100 MUg/ml. DISCUSSION AND CONCLUSION: This study indicated that
      hydroalcoholic extract of oak acorn shell acts as a potent antiangiogenic agent
      which exerts its inhibitory effect mainly through downregulation of essential
      mediators such as VEGF and MMPs.

PMID- 23137184
TI  - A Palaearctic migratory raptor species tracks shifting prey availability within
      its wintering range in the Sahel.
AB  - Mid-winter movements of up to several hundreds of kilometres are typical for many
      migratory bird species wintering in Africa. Unpredictable temporary food
      concentrations are thought to result in random movements of such birds, whereas
      resightings and recoveries of marked birds suggest some degree of site fidelity.
      Only detailed (e.g. satellite) tracking of individual migrants can reveal the
      relative importance and the causes of site choice flexibility and fidelity. The
      present study investigates how mid-winter movements of a Palaearctic-African
      migratory raptor, Montagu's harrier Circus pygargus, in the Sahel of West Africa
      are related to the availability of food resources. Thirty harriers breeding or
      hatched in northern Europe were satellite tracked (2005-2009). On average, four
      home ranges, each separated by c. 200 km, were visited during one overwinter stay
      in the Sahel. Wintering home ranges were similar in size to breeding season home
      ranges (average over wintering and breeding home range size c. 200 km(2) ), and
      harriers showed high site fidelity between years. Most preferred habitat types in
      the Sahel were mosaics of grass- and cropland, indicating similar habitat
      preferences in both the breeding- and wintering seasons. The main prey of
      Montagu's harriers in the Sahel were grasshoppers Acrididae. Highest grasshopper
      numbers in the field occurred at relatively low vegetation greenness [normalized
      difference vegetation index (NDVI) values 0.17-0.27]. We used NDVI as a proxy of
      food availability for harriers. During their overwinter stay, Montagu's harriers
      moved in a South-South-western direction between consecutive home ranges. The
      birds selected areas within the range of NDVI values associated with high
      grasshopper numbers, thus tracking a 'green belt' of predictable changes in
      highest grasshopper availability. Contrary to earlier hypotheses of random
      movements in the Sahelian-wintering quarters, the present study shows that
      Montagu's harriers visited distinct home ranges, they were site-faithful and
      tracked seasonal changes in food availability related to previous rainfall
      patterns, caused by the shifting Intertropical Convergence Zone. Itinerancy may
      be the rule rather than an exception among insectivorous birds wintering in
      African savannahs.

PMID- 23137185
TI  - Laser-induced breakdown spectroscopy.

PMID- 23137186
TI  - 2-Hydroxyethyl methacrylate inflammatory effects in human gingival fibroblasts.
AB  - AIM: To investigate the inflammatory response in human gingival fibroblasts
      (HGFs) treated with a relatively low 2-hydroxyethyl methacrylate (HEMA)
      concentration by studying reactive oxygen species (ROS) production,
      cyclooxygenase-2 (COX-2) and tumour necrosis factor-alpha (TNF-alpha) gene
      expression, and prostaglandin E2 (PGE2) release. METHODOLOGY: Cultured HGFs were
      exposed to 3 mmol L-1 HEMA for 0, 24 or 96 h. ROS production was investigated by
      flow cytometry; TNF-alpha and COX-2 gene expression was determined by RT-PCR, and
      prostaglandin E2 production was detected by an enzyme immunoassay. RESULTS: After
      24- or 96-h HEMA incubation, ROS levels were approximately eightfold and
      elevenfold higher than controls, whilst COX-2 gene expression was approximately
      twofold or fourfold higher than controls, respectively. Twenty-four-hour exposure
      enhanced TNF-alpha mRNA levels by approximately 66%, whilst after 96-h
      incubation, TNF-alpha gene expression was fivefold higher than controls. Ninety
      six-hour HEMA treatment increased PGE2 concentration in the culture medium by
      around 17% compared with controls. CONCLUSIONS: 2-Hydroxyethyl methacrylate
      treatment (3 mmol L-1) induced an inflammatory response in HGFs modulated by ROS
      production, as well as by the increase in TNF-alpha and COX-2 gene expression and
      by PGE2 release.

PMID- 23137187
TI  - Influence of castration on bladder blood flow and function during the rapid phase
      of androgen deprivation.
AB  - OBJECTIVE: This study examined the effects of androgen deprivation on bladder
      blood flow (BBF) and bladder function during the acute phase in castrated rats.
      MATERIAL AND METHODS: Nine-week-old male Wistar rats were divided into six groups
      as follows: 24 h post-sham-operation (24hPS), no operation (control), 24 h post
      castration (24hPC), 48 h post-castration (48hPC), 7 days post-castration (7dPC)
      and 12 weeks post-castration (12wPC). BBF was measured in the 24hPS, control,
      24hPC, 48hPC, 7dPC and 12wPC groups, and prostate blood flow was measured in the
      control, 24hPC, 48hPC and 7dPC groups using laser Doppler methods. In select
      groups, BBF was measured using the fluorescent microsphere method. Bladder
      function was tested in the 24hPS, control, 24hPC and 12wPC groups. The bladder
      was irrigated with saline and 0.25% acetic acid. Maximum voiding pressure and
      voiding intervals were measured. RESULTS: BBF significantly increased within 24 h
      after castration (p < 0.001); these changes did not persist beyond 24 h. However,
      prostate blood flow decreased significantly within 24 h after castration (p <
      0.001). Shortening of the voiding interval upon acetic acid stimulation was
      significantly suppressed in group 24hPC compared to the control group (p <
      0.001). The maximum voiding pressure did not significantly change in the 24hPS,
      control, 24hPC and 12wPC groups. CONCLUSIONS: During the acute phase of androgen
      deprivation following castration, BBF significantly increased and the bladder
      became receptive to stimulation. This temporary increase may be because of a
      decrease in the prostate blood flow, indicating that androgens do not directly
      affect the BBF.

PMID- 23137188
TI  - A coarse-grained MARTINI model of polyethylene glycol and of polyoxyethylene
      alkyl ether surfactants.
AB  - Nonionic surfactants are used for the isolation and purification of membrane
      proteins, as well as for the study of fundamental aspects of protein diffusion in
      membranes. Here we present a new coarse-grained model of polyethylene glycol
      (PEG) and of the family of polyoxyethylene alkyl ether (C(i)E(j)) surfactants.
      The model is compatible with the MARTINI coarse-grained force-field for lipids
      and proteins. We validate the model by comparing molecular dynamics simulations
      with experimental data. In particular, we show that the model reproduces the
      phase behavior of water-surfactant mixtures as a function of water concentration.
      We also simulate the self-assembly of two ternary mixtures that have been used
      for the experimental measure of protein diffusion coefficients. The first
      includes a cosurfactant that affects the curvature of the surfactant bilayers;
      the second is a mixture of C(i)E(j) surfactants, alkanes and water. In both
      cases, the results of self-assembly simulations are in agreement with
      experimental observations and pave the way to the use of the surfactant model in
      combination with MARTINI peptides and proteins.

PMID- 23137189
TI  - Evaluating use and outcomes of mobility technology: a multiple stakeholder
      analysis.
AB  - PURPOSE: This qualitative, multi-site study compared and contrasted the outcomes
      of mobility technology (MT) and the factors influencing these outcomes from the
      perspective of MT users, caregivers, and professionals involved in MT service
      delivery. METHOD: Qualitative focus groups were held in the USA and Canada with
      multiple stakeholder groups (consumer: n = 45, caregiver: n = 10, service
      provider: n = 10). Data were analyzed thematically. RESULTS: MT outcomes were
      conceptualized by participants as a match between expectations for MT and the
      actual outcomes experienced. Several factors influenced the match including a) MT
      features, b) environmental factors (e.g. built/physical environment, societal
      context of acceptance, MT delivery systems/policies), and c) the ability to self
      manage the interaction across person, technology and environment, which involved
      constant negotiation and strategizing. Stakeholders identified MT outcomes that
      corresponded to ICF levels including body structure and function, activity, and
      participation across environments; however, varied on their importance and
      influence on MT impact. CONCLUSIONS: The conceptual fit model and factors related
      to self-management of MT represent new knowledge and provide a framework for
      stakeholder-based evaluation of MT outcomes. Implications for MT assessment,
      service delivery, outcomes research, and interventions are discussed.

PMID- 23137190
TI  - Reliability, validity, and sensitivity measures of expanded and revised version
      of the short-form McGill Pain Questionnaire (SF-MPQ-2) in Iranian patients with
      neuropathic and non-neuropathic pain.
AB  - OBJECTIVE: The aim of this study was to assess validity, reliability, and
      sensitivity of the Persian version of the short-form McGill Pain Questionnaire 2
      (SF-MPQ-2) in patients with neuropathic and non-neuropathic pain. DESIGN:
      Beaton's guideline was used to translate and adapt the SF-MPQ-2 to Persian.
      SUBJECTS: One hundred eighty-four patients with subacute and chronic non
      neuropathic pain and 74 patients with painful diabetic peripheral neuropathy
      (total 258) attending multidisciplinary pain clinic participated in the study.
      OUTCOME MEASURES: Internal consistency and intraclass correlation coefficient
      (ICC) were estimated for participants who had completed the questionnaire in the
      morning and evening of the first day. The visual analog scale (VAS) and the
      present pain intensity (PPI) were also recorded to test convergent validity of
      the questionnaire. Sensitivity to change was examined after a standard treatment
      and validated by means of the patient global impression of change (PGIC) in
      addition to VAS and PPI. Exploratory factor analysis (EFA) was used to find
      possible components. RESULTS: Cronbach's alpha was 0.906, which showed high
      internal consistency. ICC (0.941) revealed test-retest reliability. There was
      high correlation between the mean VAS and the mean total score (r = 0.926).
      Patients in different levels of PPI and PGIC exhibited significant differences
      among their mean total scores (P < 0.05). EFA revealed four components similar to
      the original SF-MPQ-2. CONCLUSION: The Persian translation of the expanded and
      revised version of the SF-MPQ-2 is a highly reliable, sensitive, and valid
      instrument to evaluate pain in patients with and without neuropathic etiology.

PMID- 23137191
TI  - Massive Plasmodium falciparum visceral sequestration: a cause of maternal death
      in Africa.
AB  - Sequestration of Plasmodium falciparum-infected erythrocytes (PfIE) in the
      capillaries of the central nervous system (CNS) is the pathognomonic feature of
      cerebral malaria, a condition frequently leading to death. Sequestration of PfIE
      in the placental intervillous spaces is the characteristic feature of malaria in
      pregnancy and is associated with low birthweight and prematurity. Although both
      patterns of sequestration are thought to result from the expression of different
      parasite proteins involved in cytoadhesion to human receptors, scant information
      exists on whether both conditions can coexist and whether this can lead to death.
      We conducted a prospective autopsy study including all consecutive pregnancy
      related deaths in a tertiary-level referral hospital in Maputo, Mozambique,
      between October 2002 and December 2006. Extensive sampling of all major viscera
      was performed. All cases showing parasites in any of the viscera were included in
      the analysis. From 317 complete autopsies PfIEs were identified in ten women
      (3.2%). All cases showed massive accumulation of PfIE in small capillaries of the
      CNS but also in most visceral capillaries (heart, lung, kidney, uterus).
      Placental tissue, available in four cases, showed a massive accumulation of
      maternal PfIE in the intervillous space. Coma (six women) and dyspnoea (five
      women) were the most frequent presenting clinical symptoms. In conclusion,
      massive visceral sequestration of PfIE with significant involvement of the CNS is
      an infrequent but definite direct cause of maternal death in endemic areas of
      Africa. The PfIE sequestered in cerebral capillaries and the placenta coexist in
      these fatal cases. 

PMID- 23137192
TI  - Medication deserts: survey of neighborhood disparities in availability of
      prescription medications.
AB  - BACKGROUND: Only a small amount of research has focused on the relationship
      between socio-economic status (SES) and geographic access to prescription
      medications at community pharmacies in North America and Europe. To examine the
      relationship between a community's socio-economic context and its residents'
      geographic access to common medications in pharmacies, we hypothesized that
      differences are present in access to pharmacies across communities with different
      socio-economic environments, and in availability of commonly prescribed
      medications within pharmacies located in communities with different socio
      economic status. METHODS: We visited 408 pharmacies located in 168 socio
      economically diverse communities to assess the availability of commonly
      prescribed medications. We collected the following information at each pharmacy
      visited: hours of operation, pharmacy type, in-store medication availability, and
      the cash price of the 13 most commonly prescribed medications. We calculated
      descriptive statistics for the sample and fitted a series of hierarchical linear
      models to test our hypothesis that the in-stock availability of medications
      differs by the socio-economic conditions of the community. This was accomplished
      by modeling medication availability in pharmacies on the socio-economic factors
      operating at the community level in a socio-economically devise urban area.
      RESULTS: Pharmacies in poor communities had significantly higher odds of
      medications being out of stock, OR=1.24, 95% CI [1.02, 1.52]. There was also a
      significant difference in density of smaller, independent pharmacies with very
      limited stock and hours of operation, and larger, chain pharmacies in poor
      communities as compared to the middle and low-poverty communities. CONCLUSIONS:
      The findings suggest that geographic access to a neighborhood pharmacy, the type
      of pharmacy, and availability of commonly prescribed medications varies
      significantly across communities. In extreme cases, entire communities could be
      deemed "medication deserts" because geographic access to pharmacies and the
      availability of the most prescribed medications within them were very poor. To
      our knowledge, this study is first to report on the relationship between SES and
      geographic access to medications using small area econometric analysis
      techniques. Our findings should be reasonably generalizable to other urban areas
      in North America and Europe and suggest that more research is required to better
      understand the relationship of socio-economic environments and access to
      medications to develop strategies to achieve equitable medication access.

PMID- 23137193
TI  - Stem cells of the lamina propria of human oral mucosa and gingiva develop into
      mineralized tissues in vivo.
AB  - AIMS: To characterize the mineralized tissue formed constitutively in the
      supracalvarial region of scid mice by a primitive stem cell population (hOMSC)
      derived from the lamina propria of the human oral mucosa and gingiva. MATERIAL
      AND METHODS: Fibrin-hOMSC constructs were cultured for 14 days at which time
      point they were analysed for the expression of osteoblastic/cementoblastic
      markers and implanted between the skin and calvaria bones into scid mice. After 8
      weeks, the animals were sacrificed and the implantation sites analysed. RESULTS:
      Two-week-old cultures of fibrin-hOMSC constructs expressed
      osteogenic/cementogenic markers at the gene level. Macroscopic and radiographic
      examinations revealed mineralized masses at the implantation sites of fibrin
      hOMSC constructs. Histology, histochemistry and immunofluorescence showed
      mineralized masses consisting of avascular cellular and acellular matrices that
      stained positively for collagen, Ca, cementum attachment protein, cementum
      protein 1, bone sialoprotein, alkaline phosphatase, osteocalcin, amelogenin and
      ameloblastin. Positive anti-human nuclear antigen indicated the human origin of
      the cells. Atomic force microscopy depicted long prismatic structures organized
      in lamellar aggregates. CONCLUSIONS: Within the limitation of this study, the
      results indicate for the first time that fibrin-hOMSC constructs are endowed with
      the constitutive capacity to develop into mineralized tissues that exhibit
      certain similarities to cementum and bone.

PMID- 23137194
TI  - A robust experimental design method to optimize formulations of retinol solid
      lipid nanoparticles.
AB  - A robust experimental design method was developed using a response surface
      methodology and models to facilitate the development process of retinol solid
      lipid nanoparticles (SLNs). The SLNs were evaluated to determine how different
      parameters including lipid and surfactant affect size and encapsulation
      efficiency. This was conducted using factorial analysis and a robust design (RD)
      method was used to achieve optimal formulations. Two models were developed based
      on the RD principle and both mean and variance of the response characteristics
      were estimated functionally using the least squares method. They proved useful in
      formulation studies aiming to develop optimum by allowing a systematic and
      reliable design method. A model for maximizing the overall desirability
      represented by the geometric mean of all objectives was found to provide a better
      solution. The newly designed method provides useful information to characterize
      significant factors and obtain optimum formulations, thereby allowing a
      systematic and reliable design method.

PMID- 23137195
TI  - Effect of vesicle's membrane packing behaviour on skin penetration of model
      lipophilic drug.
AB  - Disaccharide glycosides synthesised from food grade resources consist of the
      hydrophilic head group of maltose or lactose and provide better hydrophilic
      lipophilic balance (HLB = 12) to the long alkyl chain derived from palm oil (PO)
      and palm kernel oil (PKO). Maltoside provides more flexibility in the vesicle's
      membrane because of its low packing density in the bilayer membrane compared to
      lactoside. The bending of the molecular structure in maltose form a less compact
      assembly for maltoside, whereas lactose is more linear in shape. Apart from
      hydrophilic moieties, packing behaviour was also governed by the hydrophobic
      moieties. PO has higher degree of unsaturation compared to PKO, thus providing
      higher fluidity in the bilayer membrane. Vesicle with high membrane flexibility
      is easier to disintegrate and deform to enhance drug penetration into the skin.
      Results showed that the glycosides delivered vitamin E (VE) into deeper skin
      layer at least two-fold higher than free VE.

PMID- 23137196
TI  - Do health workers' preferences influence their practices? Assessment of
      providers' attitude and personal use of new treatment recommendations for
      management of uncomplicated malaria, Tanzania.
AB  - BACKGROUND: Due to growing antimalarial drug resistance, Tanzania changed malaria
      treatment policies twice within a decade. First in 2001 chloroquine (CQ) was
      replaced by sulfadoxine-pyrimethamine (SP) for management of uncomplicated
      malaria and by late 2006, SP was replaced by artemether-lumefantrine (AL). We
      assessed health workers' attitudes and personal practices following the first
      treatment policy change, at six months post-change and two years later. METHODS:
      Two cross-sectional surveys were conducted in 2002 and 2004 among healthcare
      workers in three districts in South-East Tanzania using semi-structured
      questionnaires. Attitudes were assessed by enquiring which antimalarial was
      considered most suitable for the management of uncomplicated malaria for the
      three patient categories: i) children below 5; ii) older children and adults; and
      iii) pregnant women. Practice was ascertained by asking which antimalarial was
      used in the last malaria episode by the health worker him/herself and/or
      dependants. Univariate and multivariate logistic regression was used to identify
      factors associated with reported attitudes and practices towards the new
      treatment recommendations. RESULTS: A total of 400 health workers were
      interviewed; 254 and 146 in the first and second surveys, respectively. SP was
      less preferred antimalarial in hospitals and private health facilities (p<0.01)
      in the first round, and the preference worsened in the second round. In the first
      round, clinicians did not prefer SP for children below age of 5 and pregnant
      women (p<0.01), but two years later, they did not prefer it for all patient
      scenarios. SP was the most commonly used antimalarial for management of the last
      malaria episode for health workers and their dependants in both rounds, in the
      public sector (p<0.01). Health workers in the dispensaries had the highest odds
      of using SP for their own treatment [adjusted OR- first round: 6.7 (95%CI: 1.9
      23.4); crude OR- second round: 4.5 (1.5-13.3)]. CONCLUSION: Following changes in
      malaria treatment recommendations, most health workers did not prefer the new
      antimalarial drug, and their preferences worsened over time. However, many of
      them still used the newly recommended drug for management of their own or family
      members' malaria episode. This indicates that, other factors than providers'
      attitude may have more influence in their personal treatment practices.

PMID- 23137197
TI  - Nature and incidence of upper limb injuries in professional cricket players a
      prospective observation.
AB  - INTRODUCTION: Cricket is the most popular sport in India, and is gaining in
      importance in all south-east Asian countries. The purpose of this study was to
      prospectively investigate the incidence, nature, and site of acute upper limb
      injuries sustained by professional cricketers of north India over a period of one
      year. MATERIAL & METHODS: 95 cricket players (mean age 18.9 years) were
      prospectively evaluated for nature and incidence of upper limb injuries from 1st
      November 2008 to 31st October 2009. For the purpose of comparison the calculated
      injury incidence included injuries sustained during match as well as practice.
      Injuries were also grouped according to the type of cricket activities such as
      batting or fielding. RESULTS: Out of 95 players evaluated, 24 were bowlers, 19
      were batsmen, 8 were wicket keepers and the other 44 cricketers declared
      themselves as all rounders. There were a total of 16 upper limb injuries in 16
      (16.8%) players. The majority of injuries (10/16) occurred while fielding. Out of
      16 injuries, 11 were seen in hand, 3 were observed in elbow, while 2 patients
      suffered from shoulder problem. Twelve were acute injuries while 4 were
      classified as repetitive stress injuries (RSI). CONCLUSION: The incidence of
      upper limb injuries in cricketers at the professional and semi-professional level
      is significant, causing them to miss matches or practice for a significant number
      of days. This is the first study of Indian cricketers which documents the high
      incidence of upper limb injuries. The study highlights the importance of injury
      surveillance for Indian cricket. It is a concern which needs to be addressed by
      the players, coaches, teachers, administrators and medical personnel involved
      with cricket.

PMID- 23137198
TI  - CdO nanoparticle toxicity on growth, morphology, and cell division in Escherichia
      coli.
AB  - This Article deals with the toxicological study of synthesized CdO nanoparticles
      (NPs) on Escherichia coli . Characterization of the CdO NPs was done by DLS, XRD,
      TEM, and AFM studies, and the average size of NPs was revealed as 22 +/- 3 nm.
      The NPs showed bactericidal activity against E. coli. When NPs were added at
      midlog phase of growth, complete growth inhibitory concentration was found as 40
      MUg/mL. Bacterial cells changed morphological features to filamentous form with
      increasing CdO NPs exposure time, and thereafter resulted in filamentation
      associated clumping. From AFM study, severe damage of the cell surface was found
      in CdO NPs-treated cells. CdO NPs were found to interfere with the expression
      level of two conserved cell division components, ftsZ and ftsQ, in E. coli at
      both transcriptional and translational levels. Interference of CdO NPs in proper
      septum formation without affecting the nucleoid segregation was also observed in
      confocal micrographs. The elevated intracellular oxidative stress due to CdO NPs
      exposure seems to be one of the reasons for the changes in cell morphology and
      expression of division proteins in E. coli.

PMID- 23137200
TI  - Effect of cyclophosphamide exposure on the migration of primordial germ cells in
      rat fetuses.
AB  - OBJECTIVES OF THE STUDY: Effect of a single dose of cyclophosphamide on migration
      of the primordial germ cells (PGC), when they are about to reach gonadal ridge
      was investigated histochemically by staining for alkaline phosphatase. This may
      throw some light on the fate of gonadal ridge when exposed to the drug itself or
      its breakdown products such as acrolein, which is present as an environmental
      pollutant. MATERIALS AND METHODS: Twelve pregnant Charles foster rats were
      divided in to control and treatment groups and kept in separate cages. In the
      experimental group, Cyclophosphamide 20 mg/kg/body weight was injected
      intraperitoneally on day 12 of gestation. Transverse sections of fetuses
      collected on day 16 of gestation were stained for alkaline phosphatase activity.
      Outcome of the study was analysed by scanning the photomicrographs and
      represented by photomicrographs. RESULTS: An unique finding in experimental group
      in the gonadal ridge consisted of homogeneously distributed pale staining cells.
      The gonadal ridge-mesonephros junction showed a single big cluster of the PGC.
      Under higher magnification, the PGC could be identified by oval or circular shape
      with well-defined cell membranes and very distinct dark brown staining. There
      were no signs of degeneration or disintegration of these cells. CONCLUSIONS:
      Cyclophosphamide exposure led to failure of PGC to spread inwards from the
      gonadal ridge-mesonephros junction giving rise to a situation so far not reported
      in literature. The presented phenomenon will result in improper development of
      the gonads leading to infertility in an affected individual in future generation
      (Fig. 4, Ref. 18).

PMID- 23137199
TI  - Enhanced Akt phosphorylation and myogenic differentiation in PI3K p110beta
      deficient myoblasts is mediated by PI3K p110alpha and mTORC2.
AB  - Phosphoinositide 3-kinase (PI3K) is a principal regulator of Akt activation and
      myogenesis; however, the function of PI3K p110beta in these processes is not well
      defined. To address this, we investigated the role of p110beta in Akt activation
      and skeletal muscle cell differentiation. We found that Akt phosphorylation was
      enhanced in p110beta-deficient myoblasts in response to Insulin-like Growth
      Factor-I (IGF-I), epidermal growth factor, or p110alpha overexpression, as
      compared to p110beta-sufficient cells. This effect was associated with increased
      mammalian target of rapamycin complex 2 activation, even in myoblasts deficient
      in mSin1 and rictor. Conversely, in response to the G-protein-coupled receptor
      agonist lysophosphatidic acid, Akt phosphorylation was attenuated in p110beta
      deficient myoblasts. Loss of p110beta also enhanced the expression of myogenic
      markers at the myoblast stage and during the first 48 h of differentiation. These
      data demonstrate that reductions in p110beta are associated with agonist-specific
      Akt hyperactivation and accelerated myogenesis, thus revealing a negative role
      for p110beta in Akt activation and during myoblast differentiation.

PMID- 23137201
TI  - In vivo study of histamine H4 receptor in immunomodulation.
AB  - OBJECTIVE: Recently accumulating evidence has highlighted the role of histamine
      in inflammation and immune reaction by histamine H4-receptor, however the role of
      histamine via H4-receptor in immunomodulation is still unclear. Therefore, the
      present study was designed to study the immunomodulatory role of histamine H4
      receptor on antibody generation profile in rabbit. METHODS: The cohort study
      comprised of 108 rabbits in six groups. Each group consisted of 18 rabbits. Group
      I (negative control) remained non-immunized and received vehicle (sterile
      distilled water, 1 mlkg-1 * b.i.d., s.c. for 10 days (3 days prior to
      immunization until 7 days after immunization)). Group II (positive control)
      received vehicle (1 mlkg-1 * b.i.d., s.c. for 10 day), while group III-VI
      received histamine (100 ugkg-1 * b.i.d., s.c.), H4-agonist (clobenpropit
      dihydrobromide, 10 ugkg-1 * b.i.d., s.c.), and H4-antagonist (JNJ 7777120, 10
      ugkg-1 * b.i.d., i.m.) and DMSO (control group for H4R-antagonist, 1 mlkg-1 *
      b.i.d., i.m.) respectively for 10 days. Group II-VI were immunized with
      intravenous injection of sheep red blood cells (SRBC) on day 3. Immunological
      parameters [immunoglobulins (Ig), immunoglobulin M (IgM), and immunoglobulin G
      (IgG)] assessed by the whole SRBC-ELISA method and direct hemagglutination assay.
      RESULTS: Histamine could influence a detectable antibody response to SRBC as
      early as day 7 postimmunization (post-I), which lasted until day 58 post-I,
      whereas H4-receptor by H4R-antagonist treatment showed a similar profile of
      antibody (Ig, IgM, and IgG) generation as the positive control group. On the
      other hand, H4R-agonist treatment showed immunostimulant activity as compared to
      other experimental groups. The results were found statistically significant
      (p<0.01). CONCLUSIONS: Histamine H4-receptor in biological system modulates
      immunological function and stimulates antibody production only by exogenously
      administered agonists not by endogenous histamine (Tab. 1, Fig. 3, Ref. 26).

PMID- 23137202
TI  - Scolicidal activity of taurolidine for the treatment of hydatid disease.
AB  - OBJECTIVES: In this experimental study, we have evaluated in vivo and in vitro
      activities of taurolidine (TRD) against protoscolices of Echinococcus granulosus.
      BACKGROUND: Scolicidal agent application is mandatory for the interventional
      treatment of hydatid cysts. Serious adverse effects of current scolicidal agents
      forced the scientist to search for less toxic chemicals. METHODS: One milliliter
      of protoscolices suspension was administered into twelve Petri's dishes, six of
      them containing 5 ml of isotonic saline, and six of them containing 5 ml (5
      mg/ml) TRD. Forty, male Balb/c mice were divided into five equal groups. Group 1:
      protoscolices inoculated group; Group 2: protoscolices inoculated and thereafter
      immediately administered with a single dose intravenous (IV) 0.5 ml TRD (400
      mg/kg); Group 3: protoscolices inoculated and thereafter immediately administered
      with a single dose intraperitoneal (IP) 0.5 ml TRD (400 mg/kg); Group 4: three
      months after inoculating the protoscolices, one day before the sacrifice single
      dose IV 0.5 ml TRD (400 mg/kg) administered; Group 5: three months after
      inoculating the protoscolices, one day before the sacrifice single dose IP 0.5 ml
      TRD (400 mg/kg) administered. RESULTS: All the protoscolices were dead in TRD
      added Petri's Dishes in 90 minutes. In group 2 and group 3, no mouse had an
      intraabdominal hydatid cyst. CONCLUSION: The results of this study are
      encouraging us to suggest TRD as an alternative scolicidal agent. Further
      clinical studies are needed to define the effectiveness and the mode of
      application of TRD for the treatment of hydatid disease (Tab. 1, Fig. 4, Ref.
      30).

PMID- 23137203
TI  - The importance of timing in surgical treatment of unruptured symptomatic aneurysm
      of abdominal aorta.
AB  - AIM OF STUDY: Aim of this study is to define an entity of unruptured symptomatic
      AAA, to examine the influence of timing of the surgical treatment and to analyze
      the results of the treatment of unruptured symptomatic AAA in acute expansion.
      MATERIALS AND METHOD: The study is designed as retrospective analysis of 390
      operatively treated patients in the last five years at the Clinics of Vascular
      Surgery in Novi Sad. All patients were grouped into four categories: elective
      operative surgical treatment, surgical treatment 24 hours after the admission
      through the Department of Urgent Surgery with an urgent CT diagnosis (in first 2
      hours), surgical treatment within 24 hours since the admission through the
      Department of Urgent Surgery with an urgent CT diagnosis (in first 2 hours) and
      immediate surgical treatment of ruptured AAA. RESULTS: In the period from Jan 1,
      2005 to Dec 31, 2009, 390 patients with AAA were operatively treated. 89 patients
      had ruptured AAA, 52 were operated 24 hours after the urgent admission, 18
      patients were operated in the first 24 hours after the urgent admission and 231
      patients were planned for elective surgery. Mortality rates between the groups
      were as follows: elective surgery-5.1 %, patients operated 24 hours after the
      urgent admission 7.2 %, patients operated in the first 24 hours after the urgent
      admission 23 %, and patients who had ruptured AAA 34 %. CONCLUSION: Considering
      the obtained data, it can be concluded that the treatment of unruptured
      symptomatic AAA is related to a higher risk of postoperative mortality in
      relation to an elective surgery. Moreover, surgical treatment in the first 24
      hours after the urgent admission of unruptured symptomatic AAA has higher rate of
      mortality and morbidity compared to surgical treatment 24 hours after the urgent
      admission of the patients, so we can conclude that the early (semi) elective
      surgery is a method of choice for the treatment of unruptured symptomatic AAA in
      acute expansion (Tab. 2, Fig. 2, Ref. 21).

PMID- 23137204
TI  - Association of the Nramp1 gene polymorphisms and clinical forms in patients with
      tuberculosis.
AB  - BACKGROUND: Recent studies have reported that Nramp1 polymorphisms might have an
      important role in the development of tuberculosis in various populations. In this
      study, we aimed to determine Nramp1 polymorphisms in our patients with
      tuberculosis population. METHODS: We enrolled 127 patients with active
      tuberculosis and 116 healthy adults with similar age and gender. Peripheral blood
      samples were taken for determining the Nramp1 polymorphisms. By using Polymerase
      Chain Reaction (PCR) - Restriction Fragment Length Polymorphisms (RFLP)
      technique, we evaluated the polymorphisms of Nramp1 at the regions of D543N and
      INT4. RESULTS: We found that the Nramp1 polymorphisms at the region of D543N (OR:
      0.44, 95%CI: 0.09-2.06 for GA allele) were not a risk factor for tuberculosis.
      Furthermore, we could not able to detect Nramp1 polymorphism at the regions of
      INT4 (OR: 0.97, 95%CI: 0.55-1.72 for GC allele and OR: 0.90, 95%CI: 0.21-3.77 for
      CC allele). CONCLUSION: The findings of the present study do not support the
      hypothesis that Nramp1 at the regions of D543 and INT4 might play a role in
      influencing the growth of bacilli and progression of cavitary tuberculosis rather
      than susceptibility to M. tuberculosis infection. Future studies are needed to
      elucidate the role of Nramp1 variants in the pathogenesis of tuberculosis (Tab.
      3, Ref. 29).

PMID- 23137205
TI  - Maxillofacial osteosarcoma successfully treated with surgery and adjuvant
      chemotherapy in a child.
AB  - Maxillofacial osteosarcoma constitutes a minor percentage of all the head and
      neck tumors. We describe a 10 year-old girl presenting with swelling and pain in
      left maxillary region and diagnosed as low grade osteosarcoma. The patient was
      operated and given a chemotherapy protocol consisted of Cisplatin and
      Doxorubicin. After six courses of chemotherapy the patient was in complete
      remission and she is well with no evidence of disease for five years. Since high
      local recurrence rates have been reported in craniofacial osteoarcoma and we know
      the deleterious side effects of radiation therapy in children, we believe that
      best management strategy for osteosarcomas in maxillofacial region in children is
      radical surgical excision and postoperative chemotherapy (Fig. 3, Ref. 11).

PMID- 23137206
TI  - The effects of three training methods endurance, resistance and concurrent on
      adiponectin resting levels in overweighed untrained men.
AB  - The purpose of present study was to investigate the impacts of endurance,
      resistance and concurrent training on adiponectin resting levels of sedentary
      men. Forty-four sedentary students were randomly assigned to one of four groups:
      endurance training (ET; 22 +/- 0.89 yr, n=12), resistance training (RT, 21 +/-
      1.57 yr, n=9), concurrent training (CT, 21.38 +/- 2.6 yr, n=14) and control group
      (CG, n=10). After primary measurements, blood samples were drawn with subjects in
      fasting and resting state for determination of the basic level of adiponectin.
      The subjects participated in E, R and C training for 8 weeks. The ET group ran
      3d/w at 65-85 % of maximum heart rate. The exercise training session for the RT
      group consisted of 3 sets of 10-15 repetitions of weight training exercise that
      increase progressively, and repeated 3 sessions per week. The CT group trained
      exactly the sum of ET and RT groups. Correlated samples t-test and ANOVA were
      used. The results of the present study showed that after the eight-week training,
      the adiponectin levels of subjects increased in 3 groups of training but this
      increase was not significant. The level of adiponectin in CT group increased more
      than in ET and RT groups. Also, there were no significant differences in content
      of adiponectin among groups.In general, slight increases in adiponectin levels in
      training groups especially in CT group may indicate the most potential of CT
      group in increasing the levels of adiponectin in sedentary men. However more
      researches are needed to identify the effects of concurrent training (Tab. 4,
      Ref. 27).

PMID- 23137207
TI  - Analysis of the arterial anatomical variations of thyroid gland: anatomic guide
      for surgical neck dissection.
AB  - PURPOSE: Aim of this study was to establish preliminary data on the variations of
      arterial supply of thyroid gland in Karnataka population. METHODS: The anterior
      triangles in the neck of formalin fixed cadavers were dissected. The length,
      branching pattern, number and length of branches of superior thyroid artery (STA)
      were noted. We measured the length of inferior thyroid artery (ITA) from its
      point of emergence from thyrocervical trunk (TCT) to lower pole of thyroid gland.
      The length of the external carotid artery (ECA), TCT from the point of its
      emergence to the point of its branching was noted. We noted the number of
      branches from ITA and TCT. Presence of any additional artery supplying the
      thyroid gland was searched for. Difference in the length of STA and ITA between
      the two sexes and sides were noted. Statistical analysis was done by Student's t
      test. RESULTS: In our study the maximum length of STA was 5.34cm and that of ITA
      was 5.07cm and there were no statistically significant side-to-side differences
      in level of bifurcation. CONCLUSIONS: Observations of the present study on the
      course and branching pattern of arteries around thyroid gland will help in easier
      approach during thyroid surgeries and interventional techniques (Tab. 1, Fig. 3,
      Ref. 38).

PMID- 23137208
TI  - Bone morphometry.
AB  - OBJECTIVES: To compare anatomical measurements with that of radiological
      measurements. BACKGROUND: The radiological measurements are commonly used in
      clinical practice. It is well known that the anatomical measurements are more
      accurate than radiological. The comparison of anatomicoradiological measurements
      is not reported hitherto. METHODS: One human adult cadaveric femur bone was used
      for the present study. It was measured both anatomically and radiologically.
      RESULTS: In digital X- ray measurements, the length from the upper lip of fovea
      capitis to the most prominent part of greater trochanter was 87.2 mms, from the
      upper most part of greater trochanter to the isthmus it was 147.9 mms,
      mediolateral width of medullary cavity at the isthmus was 8.9 mms, the
      mediolateral width at the distal root of lesser trochanter was 18.5 mms,
      anteroposterior width of medullary cavity at the isthmus was 11.5 mms, the
      anteroposterior width at the distal root of lesser trochanter was 16.8 mms. The
      same measurements were 91.2 mms, 154.6 mms, 11.8 mms, 19.7 mms, 11.9 mms and 18.5
      mms when taken anatomically using the digital vernier caliper. CONCLUSION: The
      present study showed that in all the parameters measured the radiological values
      were slightly lesser than the anatomical values. Considering the variations in
      the values, the implants can be designed for a particular case in orthopedic
      surgery. We believe that this study adds an important reference in the scientific
      literature (Tab. 1, Fig. 2, Ref. 5).

PMID- 23137209
TI  - Management of hepatic artery aneurysms.
AB  - BACKGROUND: Hepatic artery aneurysm (HAA) is a rare clinical entity that can lead
      to potentially life threatening complications. We reported our personal
      experience of 4 cases, in which we used different procedures. METHODS: The first
      case had a pseudo-aneurysm involving the right hepatic artery. The second case
      had a pseudo-aneurysm, which was localized distal to the accidentally ligated
      right hepatic artery from the previous cholecystectomy operation. The third case
      had multiple aneurysms with accompanying dissecting abdominal aortic aneurysm.
      The fourth case had a pseudo-aneurysm originating from the proper hepatic artery.
      A covered stent was successfully placed in the case 1. In the second case, the
      right hepatic artery was ligated distal to the aneurysm. In the third case,
      vascular structures were not appropriate for vascular reconstruction, and a
      covered stent placement and embolization were unsuccessful. In the fourth case,
      ligation of the proper hepatic artery and cholecystectomy was performed. RESULTS:
      The third case with multiple aneurysms died from multi-organ failure due to
      sepsis. The remaining cases (case 1, 2, and 4) are disease free and alive.
      CONCLUSION: HAAs are more commonly observed clinical entities, and their
      treatment should be handled for each patient separately. Computerized tomography
      Angiography and intraoperative Doppler ultrasound are useful radio-diagnostics
      for determination of aneurysm and planning the operative procedure (Fig. 5, Ref.
      15).

PMID- 23137210
TI  - How confocal laser endomicroscopy can help us in diagnosing gastric lymphomas?
AB  - Primary gastric diffuse large cell lymphoma is one of the most common extranodal
      lymphomas of the gastrointestinal system. Diagnosing gastrointestinal lymphomas
      can be difficult, since there is no pathognomonic sign in endoscopy to
      distinguish it from other malignancies. In some cases biopsy can be non
      diagnostic. Therefore, multiple endoscopic examinations and biopsies can be
      necessary. With using confocal endomicroscopy, histology of the tissue can be
      seen in vivo and a range of diseases can be identified by using this technique.
      We are presenting a case, which is diagnosed as primary gastric diffuse large
      cell lymphoma during the evaluation of erythema nodosum etiology. We want to
      emphasize the role of confocal laser endomicroscopy for in vivo diagnosis of
      gastric lymphoma and directing the endoscopist for sampling the diseased mucosa.
      Confocal endomicroscopy decreases non-diagnostic rates in endoscopic biopsy and
      can be performed successfully in cases of gastric lymphoma. Pit patterns of
      gastric lymphoma, ring cell gastric carcinoma and gastric adenocarcinoma are
      similar. To best of our knowledge, this case is the fifth case of confocal laser
      endomicroscopy aided in diagnosing gastric lymphomas (Tab. 1, Fig. 2, Ref. 13).

PMID- 23137211
TI  - Demographic, metabolic, and blood pressure characteristics of living kidney
      donors spanning five decades.
AB  - While cautious criteria for selection of living kidney donors are credited for
      favorable outcomes, recent practice changes may include acceptance of less than
      ideal donors. To characterize trends in donor acceptance, the Renal and Lung
      Living Donors Evaluation (RELIVE) Study evaluated 8,951 kidney donors who donated
      between 1963 and 2007 at three major U.S. transplant centers. Over the study
      interval, there was an increase in the percentage of donors >40 years old from
      38% to 51%; donors >60 years varied between 1% and 4%. The proportion of donors
      with obesity increased from 8% to 26% and with glucose intolerance from 9% to
      25%. The percentage of hypertensive donors was consistent (5-8%). Accepted donors
      >=60 years old were more likely to have obesity, glucose intolerance, and/or
      hypertension compared to younger donors (p<0.0001). Our results demonstrate
      important trends in acceptance of older and more obese donors. The fraction of
      older donors accepted with glucose intolerance or hypertension remains small and
      for the majority includes mild elevations in glucose or blood pressure that were
      previously classified as within normal limits.

PMID- 23137212
TI  - Expansion of the gamma-gliadin gene family in Aegilops and Triticum.
AB  - BACKGROUND: The gamma-gliadins are considered to be the oldest of the gliadin
      family of storage proteins in Aegilops/Triticum. However, the expansion of this
      multigene family has not been studied in an evolutionary perspective. RESULTS: We
      have cloned 59 gamma-gliadin genes from Aegilops and Triticum species (Aegilops
      caudata L., Aegilops comosa Sm. in Sibth. & Sm., Aegilops mutica Boiss., Aegilops
      speltoides Tausch, Aegilops tauschii Coss., Aegilops umbellulata Zhuk., Aegilops
      uniaristata Vis., and Triticum monococcum L.) representing eight different
      genomes: Am, B/S, C, D, M, N, T and U. Overall, 15% of the sequences contained
      internal stop codons resulting in pseudogenes, but this percentage was variable
      among genomes, up to over 50% in Ae. umbellulata. The most common length of the
      deduced protein, including the signal peptide, was 302 amino acids, but the
      length varied from 215 to 362 amino acids, both obtained from Ae. speltoides.
      Most genes encoded proteins with eight cysteines. However, all Aegilops species
      had genes that encoded a gamma-gliadin protein of 302 amino acids with an
      additional cysteine. These conserved nine-cysteine gamma-gliadins may perform a
      specific function, possibly as chain terminators in gluten network formation in
      protein bodies during endosperm development. A phylogenetic analysis of gamma
      gliadins derived from Aegilops and Triticum species and the related genera
      Lophopyrum, Crithopsis, and Dasypyrum showed six groups of genes. Most Aegilops
      species contained gamma-gliadin genes from several of these groups, which also
      included sequences from the genera Lophopyrum, Crithopsis, and Dasypyrum. Hordein
      and secalin sequences formed separate groups. CONCLUSIONS: We present a model for
      the evolution of the gamma-gliadins from which we deduce that the most recent
      common ancestor (MRCA) of Aegilops/Triticum-Dasypyrum-Lophopyrum-Crithopsis
      already had four groups of gamma-gliadin sequences, presumably the result of two
      rounds of duplication of the locus.

PMID- 23137214
TI  - Preliminary evaluation for cancer chemopreventive and cytotoxic potential of
      naturally growing ethnobotanically selected plants of Pakistan.
AB  - CONTEXT: Natural products are a very productive source of leads for the
      development of medicines. Six Pakistani plants were chosen for study based on
      ethnobotanical data. OBJECTIVE: Exploration of important medicinal plants of
      Pakistan for cancer treatment. MATERIALS AND METHODS: The crude extracts of the
      six plants and their fractions were tested for inhibition of nuclear factor
      kappaB (NFkappaB), aromatase, and nitric oxide (NO) production in
      lipopolysaccharide (LPS)-activated murine macrophage RAW 264.7 cells, induction
      of quinone reductase 1 (QR1), agonism of retinoid X receptor, and growth
      inhibition with MCF-7, LU-1 and MDA-MB-231 cancer cells. RESULTS: Two samples of
      Withania coagulans (Stocks) Dunal (Solanaceae) demonstrated inhibition of TNF
      alpha induced activity of NFkappaB with IC50 values of 2.6 and 4.3 ug/mL,
      respectively. Two fractions from W. coagulans and Euphorbia wallichii Hook F.
      (Euphorbiaceae) aerial parts inhibited aromatase with IC50 values of 17.0 and
      17.7 ug/mL, respectively. A total of 13 samples (five from E. wallichii, one from
      Acer oblongifolium Hort. ex Dippel (Aceraceae), one from Aster thomsonii C. B.
      Clarke (Asteraceae) and six from W. coagulans aerial parts with fruits) inhibited
      NO production with IC50 values ranging from 1.3 to 15.6 ug/mL. Fourteen samples
      demonstrated induction of QR1 with CD ranging from 1.0 to 20.6 ug/mL, and a total
      of eight extracts and fractions inhibited the proliferation of cancer cells in
      culture with IC50 values ranging from 1.2 to 7.8 ug/mL. DISCUSSION AND
      CONCLUSION: Selected plants can be a valuable source of chemopreventive and
      anticancer products. W. coagulans aerial parts showed the strongest activity.

PMID- 23137216
TI  - Effect of gelatin addition on properties of pullulan films.
AB  - The gelatin was added into pullulan films to improve their performances and lower
      their cost. The gelatin addition raised the tensile strength of the gelatin
      pullulan composite films, and reduced the oxygen permeability. The cost of
      composite films was reduced comparing to that of the pullulan films. Moreover,
      the molecular interaction of the composite film was evaluated. The interactions
      of gelatin and pullulan in the composite films were detected, such as (1)
      formation of 2 glycosylated proteins; (2) improvement of beta-sheet content; (3)
      formation of the interchain hydrogen bond and a semicrystalline region.
      Therefore, the molecular interaction was the main reason for the performance
      improvement of the composite films.

PMID- 23137215
TI  - The diagnosis and conservative treatment of a complex type 3 dens invaginatus
      using cone beam computed tomography (CBCT) and 3D plastic models.
AB  - AIM: To investigate the use of 3D plastic models, printed from cone beam computed
      tomography (CBCT) data, for accurate diagnosis and conservative treatment of a
      complex case of dens invaginatus. SUMMARY: A chronic apical abscess with a
      draining sinus tract was diagnosed during the treatment planning stage of
      orthodontic therapy. Radiographic examination revealed a large radiolucent area
      associated with an invaginated right maxillary central incisor, which was found
      to contain a vital pulp. The affected tooth was strategic in the dental arch.
      Conventional periapical radiographs provided only partial information about the
      invagination and its relationship with the main root canal and with the
      periapical tissues. A limited-volume CBCT scan of the maxilla did not show
      evidence of communication between the infected invagination and the pulp in the
      main root canal, which could explain the pulp vitality. A novel method was
      adopted to allow for instrumentation, disinfection and filling of the
      invagination, without compromising the vitality of the pulp in the complex root
      canal system. The CBCT data were used to produce precise 3D plastic models of the
      tooth. These models facilitated the treatment planning process and the trial of
      treatment approaches. This approach allowed the vitality of the pulp to be
      maintained in the complex root canal space of the main root canal whilst enabling
      the healing of the periapical tissues. KEY LEARNING POINTS: Even when extensive
      periapical pathosis is associated with a tooth with type III dens invaginatus,
      pulp sensibility tests should be performed. CBCT is a diagnostic tool that may
      allow for the management of such teeth with complex anatomy. 3D printed plastic
      models may be a valuable aid in the process of assessing and planning effective
      treatment modalities and practicing them ex vivo before actually performing the
      clinical procedure. Unconventional technological approaches may be required for
      detailed treatment planning of complex cases of dens invaginatus.

PMID- 23137217
TI  - Multidimensional gas chromatography: fundamental advances and new applications.

PMID- 23137218
TI  - Factors associated with Alaska Native fatal and nonfatal suicidal behaviors 2001
      2009: trends and implications for prevention.
AB  - Suicide rates among American Indian and Alaska Native (AI/AN) young people are
      significantly higher than other ethnic groups in the United States. Not only are
      there great differences when comparing AI/AN rates and those of other Americans,
      some tribal groups have very low rates of suicide while other Native communities
      have much higher rates. Despite this obvious variability, there is little
      research to help understand the factors associated with these differences. The
      current study considers the correlates of suicidal behavior in one rural Alaska
      Native region that suffers disproportionately from suicide. The analysis
      describes suicide behavior between the years 2001-2009, and considers the
      characteristics associated with both suicide deaths and nonfatal suicidal
      behavior. In multivariate analyses we identified gender, method of suicide and
      history of previous attempt as significant predictors of fatal suicide behavior,
      similar to results obtained from analyses on the same community's data from the
      previous decade. This descriptive study can offer some insights to shape
      prevention efforts in this and other rural, tribal communities.

PMID- 23137219
TI  - Predictive validity of the MINI suicidal scale for self-harm in acute psychiatry:
      a prospective study of the first year after discharge.
AB  - The aim of the study was to explore the predictive validity of the Suicidal Scale
      of the Mini-International Neuropsychiatric Interview as a screen for suicidal
      behavior and non-suicidal self-injury following discharge from an acute
      psychiatric ward. Using a prospective, naturalistic design, the patients were
      screened with the Suicidal Scale when discharged (n = 307). At 12 months post
      discharge, the Suicidal Scale was a significant predictor of suicidal behavior (n
      = 48) and suicidal behavior+non-suicidal self-injury (n = 49) but not for non
      suicidal self-injury (n = 15). For patients without any known previous suicide
      attempts (n = 180), the Suicidal Scale was a significant predictor of suicidal
      behavior (n = 21) and suicidal behavior+non-suicidal self-injury (n = 11).
      Further research is needed to determine the overall utility of the routine
      screening of self-harm.

PMID- 23137220
TI  - Social problem solving and suicidal behavior: ethnic differences in the
      moderating effects of loneliness and life stress.
AB  - The objective of this study was to examine the combined moderating effects of
      life stress and loneliness on the association between social problem solving
      ability (SPS) and suicidal behaviors. We assessed SPS, suicidal behavior,
      loneliness, and stressful life events in a sample of 385 ethnically diverse
      college students. Overall, only loneliness moderated the association between SPS
      and suicidal behaviors. Across ethnic groups, loneliness moderated the
      association between SPS and suicidal behavior for Blacks, Whites, and Asians;
      life stress was a moderator for Hispanics. For most individuals, loneliness
      increases the strength of the association between poor problem-solving and
      suicidal behaviors. For Hispanics, life stress exacerbates this relationship.
      Ethnically-specific prevention strategies targeting loneliness and life stress
      may promote effective problem-solving, reducing suicide risk.

PMID- 23137221
TI  - Therapeutic alliance and change in suicidal ideation during treatment in
      integrated primary care settings.
AB  - A strong therapeutic alliance is considered to be an essential factor for the
      effective assessment and management of suicidal patients; however, to date this
      has received little empirical attention. The current study evaluated the
      association of future change in suicidal ideation with therapeutic alliance
      during first appointments with primary care behavioral health consultants. The
      Behavioral Health Measure (BHM; Kopta & Lowery,  2002 ) and Therapeutic Bond
      Scale (TBS; CelestHealth Solutions, 2006) were completed by 497 primary care
      patients who kept 2 to 8 appointments with the integrated behavioral health
      consultant. Results indicated that suicidal ideation generally improved over the
      course of several behavioral health appointments and that therapeutic alliance
      was rated very high by patients. Therapeutic alliance during the first
      appointment was not associated with eventual change in suicidal ideation.

PMID- 23137222
TI  - Suicide in cancer patients in California, 1997-2006.
AB  - The objective of this study was to measure suicide risk in cancer patients and
      compare it with the general population. Suicide rates were based on 1,168
      suicides in 1,123,528 cancer patients in California from 1997-2006 and were
      studied by race/ethnicity, sex, site, stage, and marital status. Suicide in
      cancer patients is 2.3 times the general population with 81% in the non-Hispanic
      Whites, and half within the first 2 years post diagnosis. In men, it rapidly
      increases by age to a high plateau in the early forties. Metastatic cancers and
      those of the prostate, lung and bronchus, pancreas, stomach, esophagus, and oral
      cavity in men and breast in women were associated with significantly higher risk.
      Cancer patients are at higher risk of suicide and should be specifically targeted
      for preventive efforts post diagnosis.

PMID- 23137223
TI  - A trait-interpersonal perspective on suicide risk in criminal offenders.
AB  - Despite elevated rates of suicide among offenders, research has yet to adequately
      address theoretically driven risk models in this population. The present study
      addresses such a gap by investigating a synthesized framework using 2 well
      developed theoretical models, the Five-Factor Model (FFM) of personality and the
      interpersonal-psychological theory of suicide (IPTS). Archival data from
      mitigation evaluations for pre-sentenced criminal offenders (n = 307) were
      analyzed using structural equation modeling (SEM). Results supported a
      hypothesized personality-IPTS-suicide framework in which neuroticism and
      extraversion predict IPTS components, namely perceived burdensomeness, thwarted
      belongingness, and acquired capability. IPTS constructs subsequently directly and
      indirectly (via suicidal ideation) predicted suicide potential. Findings have
      important implications for suicide theory, research, and risk assessment with
      offenders.

PMID- 23137224
TI  - Suicide attempts in 107 adolescents and adults with kleptomania.
AB  - Suicide attempts in kleptomania have received little investigation. This study
      examined rates, correlates, and predictors of suicide attempts in kleptomania. A
      total of 107 adolescent and adult subjects (n = 32 [29.9%] males) with DSM-IV
      kleptomania were assessed with standard measures of symptom severity, psychiatric
      comorbidity, and functional impairment. Subjects had high rates of suicide
      attempts (24.3%). The suicide attempt in 92.3% of those who attempted suicide was
      attributed specifically to kleptomania. Suicide attempts were associated with
      current and life-time bipolar disorder (p = .047) and lifetime personality
      disorder (p = .049). Individuals with kleptomania have high rates of suicide
      attempts. Bipolar disorder is associated with suicide attempts in individuals
      with kleptomania and underscores the importance of carefully assessing and
      monitoring suicidality in patients with kleptomania.

PMID- 23137227
TI  - Molecular dynamics study on the growth of structure I methane hydrate in aqueous
      solution of sodium chloride.
AB  - The structure, thermodynamic, and kinetic properties of methane hydrates formed
      from the aqueous solution of sodium chloride are investigated based on molecular
      dynamics simulations. A three-phase molecular model consisting of a slab of
      methane hydrate phase, a slab of liquid water containing sodium chloride, and a
      gas phase of methane molecules is used. The decrease in the three-phase
      coexisting temperatures (by 2-3 K) at different pressures (10-100 MPa) for
      aqueous NaCl solutions (about 2 mol %) confirms the thermodynamic inhibition of
      NaCl. The growth rate of methane hydrates in NaCl solution is found to be half to
      one-third of that in pure water. The kinetic inhibition of NaCl is found to be a
      result of the reduced water repelling at the growing interface due to the strong
      hydration of ions. Individual ions or NaCl ion pairs can replace water molecules
      to participate in the formation of the cage structures. The distortion of water
      cages due to the presence of ions may result in a reduced fraction of occupation
      of methane in the cage cavities. Our results provide useful insights into the
      mechanism of growth of methane hydrates in seawater and the desalination.

PMID- 23137228
TI  - Risk factors for prescription opioid-related death, Utah, 2008-2009.
AB  - OBJECTIVE: Utah prescription opioid death rates increased nearly fivefold during
      2000-2009. Inadequate understanding of risk factors hinders prevention. The goal
      of this study was to determine risk factors for prescription opioid death in
      Utah. DESIGN: Case-control study. Cases were 254 Utah decedents with >=1
      prescription opioid causing death during 2008-2009 with nonintentional manner of
      death (information obtained via next-of-kin interviews). Controls were 1,308 Utah
      2008 Behavioral Risk Factor Surveillance System respondents who reported
      prescription opioid use during the previous year. OUTCOME MEASURES: Exposure
      prevalence ratios (EPRs) for selected characteristics and confidence intervals
      (CIs) were calculated. RESULTS: Decedents were more likely than the comparison
      group to have used prescription pain medication more than prescribed (52.9% vs
      3.2%; EPR, 16.5; 95% CI, 9.3-23.7), obtained prescription pain medication from
      nonprescription sources (39.6% vs 8.3%; EPR, 4.8; 95% CI, 3.6-6.0), smoked daily
      (54.5% vs 9.7%; EPR, 5.6; 95% CI, 4.4-6.9), not graduated high school (18.5% vs
      6.2%; EPR, 3.0; 95% CI, 2.0-3.9), and been divorced or separated (34.6% vs 9.4%;
      EPR, 3.7; 95% CI, 3.0-4.4). Decedents were more likely to have had chronic pain
      than the comparison group (94.2% vs 31.6%; EPR, 3.0; 95% CI, 2.7-3.3).
      CONCLUSIONS: Use of pain medication outside prescription bounds was a risk factor
      for death. However, decedents were more likely to have had chronic pain, and the
      majority of both groups had obtained pain medication by prescription. Other
      factors (e.g., smoking status) might also play important roles in prescription
      opioid-related death. Prescribers should screen chronic pain patients for risk
      factors.

PMID- 23137229
TI  - Amygdalin induces apoptosis in human cervical cancer cell line HeLa cells.
AB  - Amygdalin, a naturally occurring substance, has been suggested to be efficacious
      as an anticancer substance. The effect of amygdalin on cervical cancer cells has
      never been studied. In this study, we found that the viability of human cervical
      cancer HeLa cell line was significantly inhibited by amygdalin. 4,6-Diamino-2
      phenyl indole (DAPI) staining showed that amygdalin-treated HeLa cells developed
      typical apoptotic changes. The development of apoptosis in the amygdalin-treated
      HeLa cells were confirmed by double staining of amygdalin-treated HeLa cells with
      annexin V-FITC and propidium iodide (PI) along with increase in caspase-3
      activity in these cells. Further studies indicated that antiapoptotic protein Bcl
      2 was downregulated whereas proapoptotic Bax protein was upregulated in the
      amygdalin-treated HeLa cells implying involvement of the intrinsic pathway of
      apoptosis. In vivo, amygdalin administration inhibited the growth of HeLa cell
      xenografts through a mechanism of apoptosis. The results in the present study
      suggest that amygdalin may offer a new therapeutic option for patients with
      cervical cancer.

PMID- 23137230
TI  - Insertion/deletion polymorphism of the angiotensin-converting enzyme gene in
      lupus nephritis among Mexicans.
AB  - The angiotensin (Ang)-converting enzyme (ACE) insertion/deletion (I/D)
      polymorphism determines Ang II levels, but its relationship with lupus nephritis
      (LN) in different populations is controversial. OBJECTIVE: To describe the
      allelic and genotypic distribution of the I/D polymorphism in Mexican mestizos
      with LN and assess an association with histological classes. METHODS: We included
      24 patients with systemic lupus erythematosus (SLE) without nephropathy, 41 with
      LN, 144 healthy subjects, and 36 with primary glomerulonephritis (GMN). Three ACE
      I/D polymorphism genotypes-ID, DD, and II--were detected by PCR using peripheral
      blood genomic DNA. RESULTS: Frequencies for II, ID, and DD were 0.29, 0.46, and
      0.25 in the SLE group; 0.17, 0.63, and 0.20 in the LN group; 0.14, 0.5, and 0.36
      in the GMN group; and 0.26, 0.52, and 0.22 among healthy subjects. The I/D
      polymorphism distribution according to histological class was class II: 1 II, 3
      ID, and 1 DD; class III: 2 II, 10 ID, and 1 DD; class IV: 2 II, 9 ID, and 2 DD;
      class V: 2 II, 3 ID, and 4 DD; and class VI, 1 II. The histological classes with
      at least three patients had ID genotype as the most frequent except for class V.
      CONCLUSION: No association was identified between I/D polymorphisms of ACE and
      SLE, LN, or GMN in a Mexican population.

PMID- 23137231
TI  - Therapeutic options for patients with angioedema due to C1-inhibitor
      deficiencies: from pathophysiology to the clinic.
AB  - Deficiencies in the inhibitor of the first component of human complement (C1-INH)
      are clinically associated with both hereditary angioedema (HAE) and acquired
      angioedema (AAE). The reduction in C1-INH function leads to the activation of the
      classical complement pathway and consequent complement consumption, as well as to
      the activation of the contact system and the generation of bradykinin, the
      vasoactive peptide that increases vascular permeability and causes angioedema.
      The clinical features of C1-INH deficiencies are the same in both forms of
      angioedema, and include subcutaneous non-pruritic swelling, the involvement of
      the upper respiratory tract, and abdominal pain due to partial obstruction of the
      gastrointestinal tract; however, AAE patients have no family history of
      angioedema and are characterised by the late onset of symptoms. The aim of
      therapy is to prevent or reverse angioedema. Advances in our understanding of the
      complex effects of C1-INH deficiency at molecular level have led to new targeted
      approaches to the treatment of HAE and AAE. Three new treatments have recently
      become available: a kallikrein inhibitor that prevents bradykinin release, an
      antagonist of bradykinin receptors that blocks bradykinin action, and a
      recombinant human C1-INH molecule produced in transgenic rabbits that replaces
      the deficient protein. These new drugs have expanded the armamentarium of
      treatments for angioedema due to C1-INH deficiency, which was previously limited
      to attenuated androgen, antifibrinolytic drugs, and C1-INH plasma concentrate.

PMID- 23137232
TI  - Nuclear gene targeting in Chlamydomonas using engineered zinc-finger nucleases.
AB  - The unicellular green alga Chlamydomonas reinhardtii is a versatile model for
      fundamental and biotechnological research. A wide range of tools for genetic
      manipulation have been developed for this alga, but specific modification of
      nuclear genes is still not routinely possible. Here, we present a nuclear gene
      targeting strategy for Chlamydomonas that is based on the application of zinc
      finger nucleases (ZFNs). Our approach includes (i) design of gene-specific ZFNs
      using available online tools, (ii) evaluation of the designed ZFNs in a
      Chlamydomonas in situ model system, (iii) optimization of ZFN activity by
      modification of the nuclease domain, and (iv) application of the most suitable
      enzymes for mutagenesis of an endogenous gene. Initially, we designed a set of
      ZFNs to target the COP3 gene that encodes the light-activated ion channel
      channelrhodopsin-1. To evaluate the designed ZFNs, we constructed a model strain
      by inserting a non-functional aminoglycoside 3'-phosphotransferase VIII (aphVIII)
      selection marker interspaced with a short COP3 target sequence into the nuclear
      genome. Upon co-transformation of this recipient strain with the engineered ZFNs
      and an aphVIII DNA template, we were able to restore marker activity and select
      paromomycin-resistant (Pm-R) clones with expressing nucleases. Of these Pm-R
      clones, 1% also contained a modified COP3 locus. In cases where cells were co
      transformed with a modified COP3 template, the COP3 locus was specifically
      modified by homologous recombination between COP3 and the supplied template DNA.
      We anticipate that this ZFN technology will be useful for studying the functions
      of individual genes in Chlamydomonas.

PMID- 23137233
TI  - Elderly out-of-hospital cardiac arrest has worse outcomes with a family bystander
      than a non-family bystander.
AB  - BACKGROUND: A growing elderly population along with advances in equipment and
      approaches for pre-hospital resuscitation necessitates up-to-date information
      when developing policies to improve elderly out-of-hospital cardiac arrest (OHCA)
      outcomes. We examined the effects of bystander type (family or non-family)
      intervention on 1-month outcomes of witnessed elderly OHCA patients. METHODS:
      Data from a total of 85,588 witnessed OHCA events in patients aged >=65 years,
      which occurred from 2005 to 2008, were obtained from a nationwide population
      based database. Patients were stratified into three age categories (65-74, 75-84,
      >=85 years), and the effects of bystander type (family or non-family) on initial
      cardiac rhythm, rate of bystander cardiopulmonary resuscitation (CPR), and 1
      month outcomes were assessed. RESULTS: The overall survival rate was 6.9% (65-74
      years: 9.8%, 75-84 years: 6.9%, >=85 years: 4.6%). Initial VF/VT was recorded in
      11.1% of cases with a family bystander and 12.9% of cases with a non-family
      bystander. The rate of bystander CPR was constant across the age categories in
      patients with a family bystander and increased with advancing age categories in
      patients with a non-family bystander. Patients having a non-family bystander were
      associated with significantly higher 1-month rates of survival (OR: 1.26; 95% CI:
      1.19-1.33) and favorable neurological status (OR: 1.47; 95% CI: 1.34-1.60).
      CONCLUSIONS: Elderly patient OHCA events witnessed by a family bystander were
      associated with worse 1-month outcomes than those witnessed by a non-family
      bystander. Healthcare providers should consider targeting potential family
      bystanders for CPR education to increase the rate and quality of bystander CPR.

PMID- 23137234
TI  - Troop education and avian influenza surveillance in military barracks in Ghana,
      2011.
AB  - BACKGROUND: Influenza A viruses that cause highly pathogenic avian influenza
      (HPAI) also infect humans. In many developing countries such as Ghana, poultry
      and humans live in close proximity in both the general and military populations,
      increasing risk for the spread of HPAI from birds to humans. Respiratory
      infections such as influenza are especially prone to rapid spread among military
      populations living in close quarters such as barracks making this a key
      population for targeted avian influenza surveillance and public health education.
      METHOD: Twelve military barracks situated in the coastal, tropical rain forest
      and northern savannah belts of the country were visited and the troops and their
      families educated on pandemic avian influenza. Attendants at each site was
      obtained from the attendance sheet provided for registration. The seminars
      focused on zoonotic diseases, influenza surveillance, pathogenesis of avian
      influenza, prevention of emerging infections and biosecurity. To help direct
      public health policies, a questionnaire was used to collect information on animal
      populations and handling practices from 102 households in the military barracks.
      Cloacal and tracheal samples were taken from 680 domestic and domesticated wild
      birds and analysed for influenza A using molecular methods for virus detection.
      RESULTS: Of the 1028 participants that took part in the seminars, 668 (65%)
      showed good knowledge of pandemic avian influenza and the risks associated with
      its infection. Even though no evidence of the presence of avian influenza (AI)
      infection was found in the 680 domestic and wild birds sampled, biosecurity in
      the households surveyed was very poor. CONCLUSION: Active surveillance revealed
      that there was no AI circulation in the military barracks in April 2011. Though
      participants demonstrated good knowledge of pandemic avian influenza, biosecurity
      practices were minimal. Sustained educational programs are needed to further
      strengthen avian influenza surveillance and prevention in military barracks.

PMID- 23137235
TI  - High rate of colistin resistance among patients with carbapenem-resistant
      Klebsiella pneumoniae infection accounts for an excess of mortality.
AB  - Carbapenem-resistant Klebsiella pneumoniae (CR-KP) is becoming a common cause of
      healthcare-associated infection in Italy, with high morbidity and mortality.
      Prevalent CR-KP clones and resistance mechanisms vary between regions and over
      time. Therapeutic approaches and their impact on mortality have to be
      investigated. We performed a prospective study of patients with CR-KP isolation,
      hospitalized in nine hospitals of Rome, Italy, from December 2010 to May 2011, to
      describe the molecular epidemiology, antibiotic treatment and risk factors for
      mortality. Overall, 97 patients (60% male, median age 69 years) were enrolled.
      Strains producing blaKPC-3 were identified in 89 patients, blaVIM in three
      patients and blaCTX-M-15 plus porin defects in the remaining five patients. Inter
      hospital spread of two major clones, ST512 and ST258, was found. Overall, 36.1%
      and 20.4% of strains were also resistant to colistin and tigecycline,
      respectively. Infection was diagnosed in 91 patients who received appropriate
      antibiotic treatment, combination therapy and removal of the infectious source in
      73.6%, 59.3% and 28.5% of cases, respectively. Overall, 23 different antibiotic
      regimens were prescribed. In-hospital mortality was 25.8%. Multivariate analysis
      adjusted for appropriate treatment, combination therapy and infectious-source
      removal, showed that Charlson comorbidity score, intensive-care unit onset of
      infection, bacteraemia and infection due to a colistin-resistant CR-KP strain
      were independent risk factors for mortality. The spread of clones producing K.
      pneumoniae carbapenemases, mainly ST258, is currently the major cause of CR-KP
      infection in central Italy. We observed a high rate of resistance to colistin
      that is independently associated with worse outcome.

PMID- 23137237
TI  - How Dutch medical specialists perceive the competencies and training needs of
      medical residents in healthcare management.
AB  - BACKGROUND: The Dutch postgraduate medical training has been revised to focus on
      seven competencies. The role as manager is one of these competencies. Recent
      studies show that this competency receives little attention during the residency
      training. In an earlier study, we discovered that residents perceived their
      competency as managers to be moderate. AIM: In this study, we investigated how
      medical specialists perceived the managerial competencies of medical residents
      and their need for management education. METHODS: In September 2010, a 46-item
      questionnaire was designed which examined medical specialists' perceptions of the
      competency and needs of residents in the field of medical management. Two hundred
      ninety-eight specialists were invited via email to participate. RESULTS: Hundred
      twenty-nine specialists (43.3%) responded to our survey. They rated the
      residents' competencies in contract negotiating skills, knowledge of the
      healthcare system, and specialist department poorly. They felt that residents
      were competent in updating their medical knowledge. Ninety-four percent reported
      a need for training in management among residents. Preferred topics were time
      management and healthcare organization. The preferred training method was a
      workshop given during residency by an extramural expert. CONCLUSION: Dutch
      medical specialists perceive the management competencies of residents in some
      areas to be inadequate. They feel that training in medical management during
      residency is necessary.

PMID- 23137238
TI  - Publish or perish - how to avoid perishing.

PMID- 23137239
TI  - Female student DREEMS at Jazan medical school of Saudi Arabia.

PMID- 23137240
TI  - Harnessing creativity: creating a business proposal competition for medical
      students.

PMID- 23137241
TI  - Prevention is better than cure.

PMID- 23137242
TI  - Competency-based physiotherapy education: the need for a European view?

PMID- 23137243
TI  - Mentoring and role models in recruitment and retention: a study of junior medical
      faculty perceptions.
AB  - PURPOSE: This study explored the views of junior faculty toward informing
      mentorship program development. METHOD: Mixed sampling methodologies including
      questionnaires (n = 175), focus groups (female, n = 4; male, n = 4), and
      individual interviews (female n = 10; male, n = 9) of junior faculty were
      conducted in clinical departments at one academic health sciences center.
      RESULTS: Questionnaire results indicated that having role models increased
      commitment to an academic career; mentorship experience during residency training
      was a high incentive to pursue an academic career; and junior faculty did have
      identifiable mentorship experiences. Focus group results revealed that mentoring
      as well as the presence of role models a few years ahead of the junior faculty
      would promote career development. Females preferred similar age role models who
      spoke the same language, particularly in the area of promotion. Females
      identified several challenges and issues including a lack of researcher role
      models, a range of perceptions regarding the merits of formal versus informal
      mentoring, and the idea that mentors should provide advice on promotion and
      grants. Males valued advice on finances while females wanted advice on work-life
      balance. CONCLUSIONS: Mentorship emerged as an important factor in academic
      faculty recruitment and retention, with varying perceptions of how it should be
      institutionalized. Role models were viewed as important for retention, and a
      paucity of mid-career, female researcher role models suggests a gap to be filled
      in future programmatic efforts.

PMID- 23137245
TI  - Undergraduate student assessors in a formative OSCE station.

PMID- 23137244
TI  - Mobile learning in resource-constrained environments: a case study of medical
      education.
AB  - BACKGROUND: The achievement of the millennium development goals may be
      facilitated by the use of information and communication technology in medical and
      health education. AIMS: This study intended to explore the use and impact of
      educational technology in medical education in resource-constrained environments.
      METHODS: A multiple case study was conducted in two Nepalese teaching hospitals.
      The data were analysed using activity theory as an analytical basis. RESULTS:
      There was little evidence for formal e-learning, but the findings indicate that
      students and residents adopted mobile technologies, such as mobile phones and
      small laptops, as cultural tools for surprisingly rich 'informal' learning in a
      very short time. These tools allowed learners to enhance (a) situated learning,
      by immediately connecting virtual information sources to their situated
      experiences; (b) cross-contextual learning by documenting situated experiences in
      the form of images and videos and re-using the material for later reflection and
      discussion and (c) engagement with educational content in social network
      communities. CONCLUSION: By placing the students and residents at the centre of
      the new learning activities, this development has begun to affect the overall
      educational system. Leveraging these tools is closely linked to the development
      of broad media literacy, including awareness of ethical and privacy issues.

PMID- 23137246
TI  - Attributes of residents as teachers and role models - a mixed methods study of
      stakeholders.
AB  - BACKGROUND: Residents are at the forefront of student education in the hospital,
      yet valid tools to assess their performance as teachers are lacking. AIMS: To
      develop a valid evaluation tool for assessing resident performance as educators
      for clerkship students. METHOD: A mixed-methods design was used. Focus groups of
      residents and medical students explored desired behaviors in resident educators.
      Using grounded theory, a list of behaviors was generated inductively through
      iterative review and categorized into themes. After thematic saturation,
      behaviors were rated on a Likert scale by stakeholders based on "importance" and
      "accuracy of measurement." Items which were both important and accurate were used
      in the final tool. RESULTS: Eighty-five desirable behaviors for resident
      educators were identified and consolidated into a 14-item tool. Twenty met both
      "importance" and "accuracy" criteria and fell under themes of respect, safe
      environment, balancing supervision with autonomy, relevant teaching and feedback.
      Nineteen "important" behaviors deemed not accurately measurable fell under themes
      of professionalism, communication, management skills and leadership. CONCLUSIONS:
      Evaluation of residents as teachers and development of resident-as-teacher
      curricula should emphasize aforementioned areas. Professionalism and
      organizational skills may not be measurable reliably by learners. Complementary
      tools to assess these aspects of resident performance are necessary.

PMID- 23137247
TI  - Perceived tutor benefits of teaching near peers: insights from two near peer
      teaching programmes in South East Scotland.

PMID- 23137248
TI  - New Associate Editor with responsibility for the Twelve Tips series.

PMID- 23137249
TI  - Wiki case-based learning for foundation doctors.

PMID- 23137250
TI  - The impact of lifestyle medicine continuing education on provider knowledge,
      attitudes, and counseling behaviors.
AB  - BACKGROUND: There is a need for effective continuing medical education (CME)
      programs to increase healthcare providers' knowledge and skills in lifestyle
      medicine so that healthcare providers are better equipped to assist patients in
      adopting and maintaining healthier lifestyle behaviors. AIMS: To evaluate the
      impact of five live face-to-face CME programs in lifestyle medicine on providers'
      barriers, knowledge, confidence, and professional counseling behaviors. METHODS:
      200 participants completed researcher-generated surveys before and 90 days after
      each CME program. Paired t-tests measured significant changes for all outcome
      variables, and regression analyses assessed predictors of these changes. RESULTS:
      Barriers that were targeted during the programs, i.e. lack of knowledge/skills,
      lack of materials, and perceived poor patient compliance showed highly
      significant improvement. Participants also reported significant changes in
      knowledge, confidence, and counseling behaviors in the areas of exercise and
      stress management. Some improvements occurred in areas that the CME programs did
      not target as much, i.e. nutrition, smoking, and weight management. The greatest
      predictor of change was the baseline level of scores. Those participants who
      could most benefit from change did show the largest improvements. CONCLUSIONS:
      Live CME programs can be effective in educating healthcare providers about topics
      within the rapidly expanding field of lifestyle medicine.

PMID- 23137251
TI  - Wikipedia use amongst medical students - new insights into the digital
      revolution.

PMID- 23137252
TI  - Psychometric evaluation of a knowledge based examination using Rasch analysis: an
      illustrative guide: AMEE guide no. 72.
AB  - Classical test theory has traditionally been used to carry out post-examination
      analysis of objective test data. It uses descriptive methods and aggregated data
      to help identify sources of measurement error and unreliability in a test, in
      order to minimise them. Item response theory (IRT), and in particular Rasch
      analysis, uses more complex methods to produce outputs that not only identify
      sources of measurement error and unreliability, but also identify the way item
      difficulty interacts with student ability. In this guide, a knowledge-based test
      is analysed by the Rasch method to demonstrate the variety of useful outputs that
      can be provided. IRT provides a much deeper analysis giving a range of
      information on the behaviour of individual test items and individual students as
      well as the underlying constructs being examined. Graphical displays can be used
      to evaluate the ease or difficulty of items across the student ability range as
      well as providing a visual method for judging how well the difficulty of items on
      a test match student ability. By displaying data in this way, problem test items
      are more easily identified and modified allowing medical educators to iteratively
      move towards the 'perfect' test in which the distribution of item difficulty is
      mirrored by the distribution of student ability.

PMID- 23137253
TI  - Personal and professional growth through community service.

PMID- 23137254
TI  - Implications of gender differences in motivation among medical students.

PMID- 23137255
TI  - Spanish dental students' perception of the 'educational climate'.

PMID- 23137256
TI  - Teaching and leadership opportunities for undergraduates: a cause for
      postgraduate worry?

PMID- 23137257
TI  - What motivates us to teach?

PMID- 23137258
TI  - The potential use of DREEM in assessing the perceived educational environment of
      postgraduate public health students.

PMID- 23137259
TI  - Paradise lost or paradise regained? Changes in admission system affect academic
      performance and drop-out rates of medical students.
AB  - BACKGROUND: The Austrian State medical universities had to change their admission
      system in 2005. Until this year admission to medical studies was unrestricted.
      Innsbruck Medical University chose the Eignungstest fur das Medizinstudium in der
      Schweiz (EMS) aptitude test for admission testing. AIMS AND OBJECTIVES: Did the
      implementation of a selection process affect the academic performance and drop
      out rates of students according to gender? METHODS: Two groups of students were
      compared: 'open admission' (2002-2004), and 'selected' (2006-2009). Academic
      performance was tested according to results in the final exams after year 1 (SIP
      1; SIP, summative integrierte Prufung) and after year 3 (SIP 3). Drop-out rates
      were recorded using the registration system of the university. RESULTS: Both,
      male and female 'selected' students had a higher passing rate regarding SIP 1 and
      they passed SIP 1 in shorter time and using fewer attempts than the open
      admission group. The percentage in passing SIP 3 did not change due to change in
      admission. The drop-out rates were significantly reduced for male and female
      students. 'Unselected' female students had a significantly higher drop-out ratio
      than 'unselected' male counterparts. After EMS testing, the drop-out ratios of
      female and male students were not significantly different. CONCLUSION: Selected
      applicants were more able and better motivated to study medicine.

PMID- 23137260
TI  - Distributed Simulation in surgical training: an off-site feasibility study.
AB  - BACKGROUND: Simulation offers recognised training benefits, but the cost of high
      fidelity contextualised simulation is prohibitive and its accessibility limited
      to specialised Distributed Simulation centres. Distributed simulation (DS) is an
      innovative concept of low-cost, portable and high-fidelity contextualised
      simulation. However, it has previously only been trialled at a central London
      teaching hospital. AIMS: (1) To explore the off-site feasibility of DS. (2) To
      determine the response of end-users to DS. METHODS: A DS naive researcher
      recreated a standardised porcine laparoscopic cholecystectomy scenario at a
      District General Hospital using DS. A research diary detailed the logistical
      feasibility of the project, whilst mixed methods were used to determine the
      response of the 10 surgeons who completed the full-team simulation. RESULTS: DS
      is feasible off-site with end-users comparing it favourably to their previous
      simulation experiences. Surgeons perceived DS as being most useful for building
      the operative confidence of juniors between learning the basics on a bench top
      model and before entering the operating theatre. CONCLUSIONS: DS has the
      potential to provide high-fidelity contextualised simulation as an adjunct to,
      and not a replacement for, surgical training. Unlike other modalities, it is low
      cost and portable, thereby addressing concerns over affordability and
      accessibility.

PMID- 23137261
TI  - Finding direction: what influences medical students in their final career
      speciality choices?

PMID- 23137262
TI  - Interns in emergency: experience does not mean confidence.

PMID- 23137263
TI  - Clinical skills examination as part of the Taiwan National Medical Licensing
      Examination.

PMID- 23137264
TI  - Do trainees value feedback in case-based discussion assessments?
AB  - BACKGROUND: Feedback is important in learning, including in workplace-based
      assessments. AIM: To explore trainee's perceptions of the educational value of
      case-based discussions (CBDs) specifically focusing on feedback. METHODS: An
      online questionnaire and interviews obtaining detailed descriptions of paediatric
      trainees at UK specialist training levels 1 and 2 views and experiences were
      used. Qualitative data were analysed using a thematic framework analysis.
      RESULTS: Trainees viewed CBDs as educationally valuable, aiding reflective
      learning, improving decision making skills and effecting a change in practice.
      Opinions varied regarding how useful they found the feedback. Feedback was
      perceived as more valuable from assessors who had a positive attitude towards
      CBDs, understood the process and had experience in leading them. Time constraints
      and assessments performed in less suitable environments had a negative impact on
      feedback. Trainees felt the choice of case played an important role, with
      challenging cases resulting in more beneficial feedback. CONCLUSIONS: CBD
      assessments provide a new opportunity for good quality learning and feedback,
      providing there is a commitment to the educational aspects of the process by both
      trainer and trainee. Trainers being aware of the qualities of the discussions
      that result in successful feedback, could significantly improve their educational
      value.

PMID- 23137265
TI  - Colloidal particles in competition for stabilizer: a solvent relaxation NMR study
      of polymer adsorption and desorption.
AB  - The competitive adsorption of poly(vinylpyrrolidone) onto silica and alumina
      modified silica particles was studied using solvent relaxation nuclear magnetic
      resonance. The additive nature of the measured relaxation rate enabled
      predictions to be made of the relaxation rate in different polymer adsorption
      scenarios. Preferential adsorption of the poly(vinylpyrrolidone) onto the
      unmodified silica particles occurred when there was insufficient polymer in the
      system to coat the entire available surface area. Desorption was also found to
      occur when the polymer was initially adsorbed upon the alumina-modified particle
      and silica particles were added.

PMID- 23137266
TI  - Incidence and magnitude of bacteraemia caused by flossing and by scaling and root
      planing.
AB  - AIM: (1) Investigate incidence, magnitude and bacterial diversity of bacteraemia
      due to flossing compared with scaling and root planing (SRP) and (2) Identify any
      associations with clinical parameters. MATERIALS AND METHODS: Full-mouth flossing
      and single quadrant SRP were performed at separate visits for 30 patients with
      chronic periodontitis. Baseline blood samples and at 30 s and 10 min. after
      completion of flossing, 5 min. after initiation of SRP and 30 s and 10 min. after
      completion of SRP were obtained. Total bacteraemia and viridans streptococcal
      bacteraemia (VSB) were investigated. RESULTS: Total bacteraemia incidence was 30%
      for flossing and 43.3% for SRP (no significant difference; p = 0.21). Flossing
      and SRP caused the same incidence of VSB (26.7%). Flossing caused a higher mean
      magnitude of total bacteraemia than SRP (7.4 +/- 16.2 CFU/ml versus 2 +/- 3.4
      CFU/ml), but the difference was not significant (p = 0.2). Flossing caused a
      higher mean magnitude of VSB than SRP (1.2 +/- 1.6 CFU/ml versus 0.4 +/- 0.2
      CFU/ml), but the difference was not significant (p = 0.09). Viridans streptococci
      comprised 11.4% of flossing bacteraemia isolates and 7.6% in SRP. No correlations
      were found between clinical parameters and incidence or magnitude of bacteraemia
      following flossing. Gingival inflammation was significantly associated with
      incidence of total bacteraemia (p = 0.01) and VSB (p = 0.001) following SRP. No
      correlations were found for any parameter and magnitude of total bacteraemia or
      VSB following SRP. CONCLUSIONS: No differences were found between flossing and
      SRP in the incidence or magnitude of total bacteraemia or VSB. This finding is
      important in the ongoing re-evaluation of antibiotic prophylaxis to prevent
      infective endocarditis.

PMID- 23137267
TI  - Non-26S proteasome proteolytic role of ubiquitin in plant endocytosis and
      endosomal trafficking(F).
AB  - The 76 amino acid protein ubiquitin (Ub) is highly conserved in all eukaryotic
      species. It plays important roles in many cellular processes by covalently
      attaching to the target proteins. The best known function of Ub is marking
      substrate proteins for degradation by the 26S proteasome. In fact, other
      consequences of ubiquitination have been discovered in yeast and mammals, such as
      membrane trafficking, DNA repair, chromatin modification, and protein kinase
      activation. The common mechanism underlying these processes is that Ub serves as
      a signal to sort proteins to the vacuoles or lysosomes for degradation as opposed
      to 26S proteasome-dependent degradation. To date, several reports have indicated
      that a similar function of Ub also exists in plants. This review focuses on a
      summary and analysis of the recent research progress on Ub acting as a signal to
      mediate endocytosis and endosomal trafficking in plants.

PMID- 23137268
TI  - Consumption of bee pollen affects rat ovarian functions.
AB  - The aim of this study was to examine possible effects of bee pollen added to the
      feed mixture (FM) on rat ovarian functions (secretion activity and apoptosis). We
      evaluated the bee pollen effect on the release of insulin-like growth factor I
      (IGF-I) and steroid hormones (progesterone and estradiol), as well as on the
      expression of markers of apoptosis (Bcl-2, Bax and caspase-3) in rat ovarian
      fragments. Female rats (n = 15) were fed during 90 days by FM without or with
      rape seed bee pollen in dose either 3 kg/1000 kg FM or 5 kg/1000 kg FM. Fragments
      of ovaries isolated from rats of each group (totally 72 pieces) were incubated
      for 24 h. Hormonal secretion into the culture medium was detected by RIA. The
      markers of apoptosis were evaluated by Western blotting. It was observed that IGF
      I release by rat ovarian fragments was significantly (p < 0.05) decreased; on the
      other hand, progesterone and estradiol secretion was increased after bee pollen
      treatment at dose 5 kg/1000 kg FM but not at 3 kg/1000 FM. Accumulation of Bcl-2
      was increased by bee pollen added at 3 kg/1000 kg FM, but not at higher dose.
      Accumulation of Bax was increased in ovaries of rats fed by bee pollen at doses
      either 3 or 5 kg/1000 kg FM, whilst accumulation of caspase-3 increased after
      feeding with bee pollen at dose 5 kg/1000 kg FM, but not at 3 kg/1000 kg FM. Our
      results contribute to new insights regarding the effect of bee pollen on both
      secretion activity (release of growth factor IGF-I and steroid hormones
      progesterone and estradiol) and apoptosis (anti- and pro-apoptotic markers Bcl-2,
      Bax and caspase-3). Bee pollen is shown to be a potent regulator of rat ovarian
      functions. 

PMID- 23137269
TI  - Quantitative Trait Locus (QTL) meta-analysis and comparative genomics for
      candidate gene prediction in perennial ryegrass (Lolium perenne L.).
AB  - BACKGROUND: In crop species, QTL analysis is commonly used for identification of
      factors contributing to variation of agronomically important traits. As an
      important pasture species, a large number of QTLs have been reported for
      perennial ryegrass based on analysis of biparental mapping populations. Further
      characterisation of those QTLs is, however, essential for utilisation in varietal
      improvement programs. RESULTS: A bibliographic survey of perennial ryegrass trait
      dissection studies identified a total of 560 QTLs from previously published
      papers, of which 189, 270 and 101 were classified as morphology-, physiology- and
      resistance/tolerance-related loci, respectively. The collected dataset permitted
      a subsequent meta-QTL study and implementation of a cross-species candidate gene
      identification approach. A meta-QTL analysis based on use of the BioMercator
      software was performed to identify two consensus regions for pathogen resistance
      traits. Genes that are candidates for causal polymorphism underpinning perennial
      ryegrass QTLs were identified through in silico comparative mapping using rice
      databases, and 7 genes were assigned to the p150/112 reference map. Markers
      linked to the LpDGL1, LpPh1 and LpPIPK1 genes were located close to plant size,
      leaf extension time and heading date-related QTLs, respectively, suggesting that
      these genes may be functionally associated with important agronomic traits in
      perennial ryegrass. CONCLUSIONS: Functional markers are valuable for QTL meta
      analysis and comparative genomics. Enrichment of such genetic markers may permit
      further detailed characterisation of QTLs. The outcomes of QTL meta-analysis and
      comparative genomics studies may be useful for accelerated development of novel
      perennial ryegrass cultivars with desirable traits.

PMID- 23137270
TI  - Characterization of human adipose tissue-resident hematopoietic cell populations
      reveals a novel macrophage subpopulation with CD34 expression and mesenchymal
      multipotency.
AB  - Adipose tissue (AT) is composed of mature adipocytes and stromal vascular
      fraction (SVF) cells, including adipose stem/stromal cells (ASCs). We
      characterized hematopoietic cells residing in human nonobese AT by analyzing the
      SVF isolated from human lipoaspirates and peripheral blood (PB). Flow cytometry
      revealed that AT-resident hematopoietic cells consisted of AT-resident
      macrophages (ATMs) or lymphocytes with a negligible number of granulocytes. AT
      resident lymphocytes were composed of helper T cells and natural killer cells.
      Almost no B cells and few cytotoxic T cells were observed in nonobese AT. More
      than 90% of ATMs were M2 state CD206(+) macrophages (CD45(+)/CD14(+)) that were
      located in the periendothelium or interstitial spaces between adipocytes. We also
      discovered a novel subpopulation of CD34(+)/CD206(+) ATMs (11.1% of CD206(+)ATMs)
      that localized in the perivascular region. Microarray of noncultured
      CD34(+)/CD206(+) ATMs, CD34(-)/CD206(+) ATMs, CD45(-)/CD31(-)/CD34(+) ASCs, and
      PB-derived circulating monocytes revealed that CD34(+)/CD206(+) ATMs shared
      characteristics with ASCs and circulating monocytes. Unlike CD34(-)/CD206(+)
      ATMs, CD34(+)/CD206(+) ATMs could grow in adherent culture and were capable of
      differentiating into multiple mesenchymal (adipogenic, osteogenic, and
      chondrogenic) lineages, similar to ASCs. CD34(+)/CD206(+) ATMs grew rapidly and
      lost expression of CD45, CD14, and CD206 by passage 3, which resulted in a
      similar expression profile to ASCs. Thus, this novel ATM subpopulation
      (CD45(+)/CD14(+)/CD34(+)/CD206(+)) showed distinct biological properties from
      other ATMs and circulating monocytes/macrophages. The CD34(+)/CD206(+) ATMs
      possessed characteristics similar to ASCs, including adherence, localization,
      morphology, and mesenchymal multipotency. This AT-resident subpopulation may have
      migrated from the bone marrow and may be important to tissue maintenance and
      remolding.

PMID- 23137271
TI  - Ultrasonic monitoring of the effect of sodium hypochlorite on the elasticity of
      dentine.
AB  - AIM: To determine the change in ultrasonic velocity of dentine after the
      application of 5% NaOCl. METHODOLOGY: Twenty standardized plano-parallel dentine
      bars were divided into two groups. Dentine bars were wetted on only one surface.
      The test group (n = 10) was irrigated with 5% NaOCl, and the control group, (n =
      10) with saline. Ultrasonic velocities before and after irrigation were compared
      to determine the change in the modulus of elasticity. Finally, dentine bars were
      loaded until failure in a 3-point bending test. Paired t-test and the mean of
      differences were used to assess the statistical significance between the groups.
      RESULTS: The mean ultrasonic velocity decreased by 1.4% after the application of
      NaOCl; no change was observed for saline. The mean velocity reduction of 49 m s-1
      was found to be highly significant (P = 0.004). The ultrasonically derived
      modulus of elasticity decreased by 2.6% compared to the initial value of 17.8
      GPa. However, the observed reduction in elasticity derived from the 3-point
      bending test was not significant (P = 0.238). CONCLUSIONS: NaOCl reduced the
      ultrasonic velocity of dentine and the ultrasonically derived modulus of
      elasticity.

PMID- 23137272
TI  - Gram-positive bacteria as an antigen topically applied into gingival sulcus of
      immunized rat accelerates periodontal destruction.
AB  - BACKGROUND AND OBJECTIVE: Periodontitis is generally accepted to relate to gram
      negative bacteria, and the host defense system influences its onset and
      progression. However, little is known about the relation between gram-positive
      bacteria and periodontitis. In this study, we topically applied gram-positive and
      gram-negative bacterial suspensions to the gingival sulcus in rats after
      immunization, and then histopathologically examined their influence on
      periodontal destruction. MATERIALS AND METHODS: Rats previously immunized with
      heat-treated and sonicated Staphylococcus aureus or Aggregatibacter
      actinomycetemcomitans were used as immunized groups. The non-immunized group
      received only sterile phosphate-buffered saline. In each animal, S. aureus or A.
      actinomycetemcomitans suspension was applied topically to the palatal gingival
      sulcus of first molars every 24 h for 10 d. Blood samples were collected and the
      serum level of anti-S. aureus or anti-A. actinomycetemcomitans immunoglobulin G
      (IgG) antibodies was determined by enzyme-linked immunosorbent assay. The first
      molar regions were resected and observed histopathologically. Osteoclasts were
      stained with tartrate-resistant acid phosphatase (TRAP). The formation of immune
      complexes was confirmed by immunohistological staining of C1qB. RESULTS: Serum
      levels of anti-S. aureus and anti-A. actinomycetemcomitans IgG antibodies in the
      immunized groups were significantly higher than those in the non-immunized groups
      were. The loss of attachment, increase in apical migration of the junctional
      epithelium, and decreases in alveolar bone level and number of TRAP-positive
      multinuclear cells in each immunized group were significantly greater than in
      each non-immunized group. The presence of C1qB was observed in the junctional
      epithelium and adjacent connective tissue in the immunized groups. CONCLUSIONS:
      Heat-treated and sonicated S. aureus and A. actinomycetemcomitans induced
      attachment loss in rats immunized with their suspensions. Our results suggest
      that not only gram-negative but also gram-positive bacteria are able to induce
      periodontal destruction.

PMID- 23137273
TI  - Editorial comment for Anderson et al.

PMID- 23137274
TI  - Synergistic and cytotoxic action of indole alkaloids produced from elicited cell
      cultures of Catharanthus roseus.
AB  - CONTEXT: Catharanthus roseus (L.) G. Don (Apocynaceae) is a medicinal plant that
      produces more than 130 alkaloids, with special attention given to the production
      of the anti-hypertensive monomeric indole alkaloids, serpentine and ajmalicine,
      and the antitumor dimeric alkaloids, vinblastine and vincristine. OBJECTIVE: This
      study evaluated the cytotoxic activity of the indole alkaloid-enriched bioactive
      extract obtained from suspension cultured-cells of C. roseus elicited with methyl
      jasmonate (MJ) and cyclodextrins (CDs) in three cell lines: JURKAT E.6 human
      lymphocytic leukemia, THP-1 human monocytic leukemia and BL 1395 non-tumor human
      B-cell line. MATERIALS AND METHODS: An indole alkaloid-enriched bioactive extract
      was obtained from C. roseus cell cultures elicited with MJ and CDs. The indole
      alkaloids were identified using an HPLC-diode array system coupled to a time-of
      flight mass spectrometer using electrospray ionization (ESI) source. The
      cytotoxic assays were made using the colorimetric assay 2, 3-bis (2-methoxy-4
      nitro-5-sulfophenyl)-S-[(phenylamino)carbonyl]-2 tetrazolium hydroxide (XTT).
      RESULTS: Four indole alkaloids were identified (catharanthine, ajmalicine,
      tabersonine and lochnericine) but only catharanthine and ajmalicine were
      quantified. The concentration of the indole alkaloid-enriched bioactive extract
      that inhibited cell growth by 50% was 211 and 210 ng/mL for the JURKAT E.6 and
      THP-1 cell lines, respectively. DISCUSSION AND CONCLUSION: The results confirm
      that the powerful antitumor activity of this indole alkaloid-enriched bioactive
      extract is not due to the effect of a single compound but depends on the
      synergistic action of the four compounds identified.

PMID- 23137275
TI  - Ambient low temperature plasma etching of polymer films for secondary ion mass
      spectrometry molecular depth profiling.
AB  - The feasibility of a low temperature plasma (LTP) probe as a way to prepare
      polymer bevel cross sections for secondary ion mass spectrometry (SIMS)
      applications was investigated. Poly(lactic acid) and poly(methyl methacrylate)
      films were etched using He LTP, and the resulting crater walls were depth
      profiled using time-of-flight secondary ion mass spectrometry (ToF-SIMS) to
      examine changes in chemistry over the depth of the film. ToF-SIMS results showed
      that while exposure to even 1 s of plasma resulted in integration of atmospheric
      nitrogen and contaminants to the newly exposed surface, the actual chemical
      modification to the polymer backbone was found to be chemistry-dependent. For
      PLA, sample modification was confined to the top 15 nm of the PLA surface
      regardless of plasma exposure dose, while measurable change was not seen for
      PMMA. The confinement of chemical modification to 15 nm or less of the top
      surface suggests that LTP can be used as a simple method to prepare cross
      sections or bevels of polymer thin films for subsequent analysis by surface
      sensitive molecular depth profiling techniques such as SIMS, X-ray photoelectron
      spectroscopy (XPS), and other spatially resolved mass spectrometric techniques.

PMID- 23137276
TI  - A novel matrix for the short-term storage of cells: utility in drug metabolism
      and drug transporter studies with rat, dog and human hepatocytes.
AB  - 1. The SureTran matrix is a novel method facilitating short-term maintenance of
      fresh primary hepatocyte cellular function and offers the potential use of
      primary cells "as fresh" for several days post isolation. In the study presented,
      the maintenance of several key phase I and II drug metabolizing enzyme and drug
      transporter activities is demonstrated with rat and dog hepatocytes preserved for
      up to 7 days after cell isolation. 2. Intrinsic clearance values were determined
      for 60 new chemical entities using rat hepatocytes freshly isolated at
      AstraZeneca and rat hepatocytes prepared at the facilities of Abcellute Ltd
      (SureTran purveyors), stored and incubated 24 hours after isolation. A very good
      correspondence in the intrinsic clearance values underlines the utility of the
      cell maintenance matrix. 3. For human hepatocytes many of the enzyme activities
      assayed were well maintained for 7 days of storage but some declined to below 50%
      of initial values between day 4 and 7 of storage. Human OATP1B1 activity was only
      determined with one batch and declined to 51% of the initial test value by day 4
      and further down to 35% by day 7.

PMID- 23137277
TI  - Three-dimensional density functional study of heterogeneous nucleation of
      droplets on solid surfaces.
AB  - We present a three-dimensional density functional approach to investigate
      heterogeneous nucleation behaviors of Lennard-Jones fluid on solid walls. In the
      theoretical calculation, fast Fourier transforms to compute the convolutions of
      Euler-Lagrange equation enables a high-efficient algorithm in three-dimensional
      space. The density distributions of a growing nucleus are presented to account
      for the nucleation process. Accordingly, the structures of nucleated droplet and
      surrounding supersaturated vapor on different walls are analyzed, and the
      corresponding free energy barriers and the critical radii are obtained to
      evaluate the difficulty of droplet formation. Since the theoretical approach is
      strictly constructed in three-dimensional space, and the liquid-solid, vapor
      solid, and vapor-liquid interfacial tensions as well as the vapor-liquid-solid
      line tension are entirely integrated into the excess free energy expression, the
      present approach provides a flexible and efficient tool for studying
      heterogeneous nucleation.

PMID- 23137278
TI  - Genetic and biochemical basis for alternative routes of tocotrienol biosynthesis
      for enhanced vitamin E antioxidant production.
AB  - Vitamin E tocotrienol synthesis in monocots requires homogentisate geranylgeranyl
      transferase (HGGT), which catalyzes the condensation of homogentisate and the
      unsaturated C20 isoprenoid geranylgeranyl diphosphate (GGDP). By contrast,
      vitamin E tocopherol synthesis is mediated by homogentisate phytyltransferase
      (HPT), which condenses homogentisate and the saturated C20 isoprenoid phytyl
      diphosphate (PDP). An HGGT-independent pathway for tocotrienol synthesis has also
      been shown to occur by de-regulation of homogentisate synthesis. In this paper,
      the basis for this pathway and its impact on vitamin E production when combined
      with HGGT are explored. An Arabidopsis line was initially developed that
      accumulates tocotrienols and homogentisate by co-expression of Arabidopsis
      hydroxyphenylpyruvate dioxygenase (HPPD) and Escherichia coli bi-functional
      chorismate mutase/prephenate dehydrogenase (TyrA). When crossed into the vte2-1
      HPT null mutant, tocotrienol production was lost, indicating that HPT catalyzes
      tocotrienol synthesis in HPPD/TyrA-expressing plants by atypical use of GGDP as a
      substrate. Consistent with this, recombinant Arabidopsis HPT preferentially
      catalyzed in vitro production of the tocotrienol precursor geranylgeranyl
      benzoquinol only when presented with high molar ratios of GGDP:PDP. In addition,
      tocotrienol levels were highest in early growth stages in HPPD/TyrA lines, but
      decreased strongly relative to tocopherols during later growth stages when PDP is
      known to accumulate. Collectively, these results indicate that HPPD/TyrA-induced
      tocotrienol production requires HPT and occurs upon enrichment of GGDP relative
      to PDP in prenyl diphosphate pools. Finally, combined expression of HPPD/TyrA and
      HGGT in Arabidopsis leaves and seeds resulted in large additive increases in
      vitamin E production, indicating that homogentisate concentrations limit HGGT
      catalyzed tocotrienol synthesis.

PMID- 23137279
TI  - Lipoprotein(a), polymorphisms in the LPA gene, and incident venous
      thromboembolism among 21483 women.

PMID- 23137280
TI  - Higher Environmental Relative Moldiness Index (ERMI) values measured in homes of
      asthmatic children in Boston, Kansas City, and San Diego.
AB  - OBJECTIVE: Mold in water-damaged homes has been linked to asthma. Our objective
      was to test a new metric to quantify mold exposures in asthmatic children's homes
      in three widely dispersed cities in the United States. METHODS: The Environmental
      Relative Moldiness Index (ERMI) metric was created by the US Environmental
      Protection Agency, with assistance by the Department of Housing and Urban
      Development (HUD), to quantify mold contamination in US homes. The ERMI values in
      homes of asthmatic children were determined for the three widely dispersed cities
      of Boston, Kansas City, and San Diego. RESULTS: Asthmatic children in Boston (n =
      76), Kansas City (n = 60), and San Diego (n = 93) were found to be living in
      homes with significantly higher ERMI values than were found in homes randomly
      selected during the 2006 HUD American Healthy Homes Survey (AHHS) from the same
      geographic areas (n = 34, 22, and 28, respectively). Taken together, the average
      ERMI value in the homes with an asthmatic child was 8.73 compared to 3.87 for the
      AHHS homes. In addition, Kansas City homes of children with "Mild, Moderate, or
      Severe Persistent Asthma" had average ERMI value of 12.4 compared to 7.9 for
      homes of children with only "Mild Intermittent Asthma." Aspergillus niger was the
      only mold of the 36 tested which was measured in significantly greater
      concentration in the homes of asthmatic children in all three cities. CONCLUSION:
      High ERMI values were associated with homes of asthmatic children in three widely
      dispersed cities in the United States.

PMID- 23137281
TI  - Self-sampling is appropriate for detection of Staphylococcus aureus: a validation
      study.
AB  - BACKGROUND: Studies frequently use nasal swabs to determine Staphylococcus
      aureus carriage. Self-sampling would be extremely useful in an outhospital
      research situation, but has not been studied in a healthy population. We studied
      the similarity of self-samples and investigator-samples in nares and pharynxes of
      healthy study subjects (hospital staff) in the Netherlands. METHODS: One hundred
      and five nursing personnel members were sampled 4 times in random order after
      viewing an instruction paper: 1) nasal self-sample, 2) pharyngeal self-sample, 3)
      nasal investigator-sample, and 4) pharyngeal investigator-sample. RESULTS: For
      nasal samples, agreement is 93% with a kappa coefficient of 0.85 (95% CI 0.74
      0.96), indicating excellent agreement, for pharyngeal samples agreement is 83%
      and the kappa coefficient is 0.60 (95% CI 0.43-0.76), indicating good agreement.
      In both sampling sites self-samples even detected more S. aureus than
      investigator-samples. CONCLUSIONS: This means that self-samples are appropriate
      for detection of Staphylococcus aureus and methicillin-resistant Staphylococcus
      aureus.

PMID- 23137282
TI  - Transforming pluripotency: an exon-level study of malignancy-specific transcripts
      in human embryonal carcinoma and embryonic stem cells.
AB  - To circumvent difficulties of isolating pure populations of cancer stem cells
      (CSCs) for the purpose of identifying malignancy-specific gene expression, we
      have compared exon-resolution transcriptomic profiles of 5 embryonal carcinoma
      (EC) cell lines, a histological subtype of germ cell tumor (GCT), to their
      nonmalignant caricature, specifically 6 human embryonic stem (ES) cell lines.
      Both cell types are readily accessible, and were purified for undifferentiated
      cells only. We identified a set of 28 differentially expressed genes, many of
      which had cancer and stemness roles. Overexpression of the recently discovered
      pluripotency gene NR5A2 in malignant EC cells revealed an intriguing indication
      of how WNT-mediated dysregulation of pluripotency is involved with malignancy.
      Expression of these 28 genes was further explored within 2 publically available
      data sets of primary EC tumors and normal testis. At the exon-level, alternative
      splicing events were detected in ZNF195, DNMT3B, and PMF1, and alternative
      promoters were detected for ASH2L and ETV5. These events were validated by
      reverse transcriptase-polymerase chain reaction-based methods in EC and ES lines,
      where the alternative splicing event in the de novo DNA methyltransferase DNMT3B
      may have functional consequences. In conclusion, we have identified malignancy
      specific gene expression differences within a rigorous pluripotent stem cell
      context. These findings are of particular interest for both GCT and ES cell
      biology, and, in general, to the concept of CSCs.

PMID- 23137283
TI  - Preventive effects of trehalose on osteoclast differentiation in rat
      periodontitis model.
AB  - AIM: Trehalose, which is a disaccharide formed by a 1,1 linkage of two glucose
      molecules, was suggested to have a suppressive effect on bone resorption. In this
      study, we examined the effects of topical application of trehalose on osteoclast
      differentiation in a rat periodontitis model. MATERIAL AND METHODS: Rats were
      divided into four groups. One group received no treatment. In the other groups,
      experimental periodontitis was induced by ligature placement. These rats with
      experimental periodontitis received topical application of pure water (vehicle
      group), 30 mg/ml trehalose solution (30 mg/ml trehalose group) or 60 mg/ml
      trehalose solution (60 mg/ml trehalose group) to the gingival sulcus
      respectively. RESULTS: The vehicle group showed higher numbers of
      polymorphonuclear leucocytes, receptor activator of nuclear factor kappa B ligand
      (RANKL)-positive cells and osteoclasts compared with the no treatment group
      respectively. Trehalose-applied groups exhibited lower numbers of these cells
      compared with the vehicle group. Gene expressions of tumour necrosis factor
      alpha, RANKL and toll-like receptor 4 were suppressed by trehalose. In addition,
      protein expressions of RANKL inducing pathway were less activated by trehalose.
      CONCLUSION: Topical application of trehalose could suppress osteoclast
      differentiation by inactivation of RANKL inducing pathway in the rat
      periodontitis model.

PMID- 23137284
TI  - Polymer micelles with hydrophobic core and ionic amphiphilic corona. 1.
      Statistical distribution of charged and nonpolar units in corona.
AB  - Polymer micelles with hydrophobic polystyrene (PS) core and ionic amphiphilic
      corona from charged N-ethyl-4-vinylpyridinium bromide (EVP) and uncharged 4
      vinylpyridine (4VP) units spontaneously self-assembled from PS-block-poly(4VP
      stat-EVP) macromolecules in mixed dimethylformamide/methanol/water solvent. The
      fraction of statistically distributed EVP units in corona-forming block is beta =
      [EVP]/([EVP]+[4VP]) = 0.3-1. Micelles were transferred into water via dialysis
      technique, and pH was adjusted to 9, where 4VP is insoluble. Structural
      characteristics of micelles were investigated both experimentally and
      theoretically as a function of corona composition beta. Methods of dynamic and
      static light scattering, electrophoretic mobility measurements, sedimentation
      velocity, transmission electron microscopy, and UV spectrophotometry were
      applied. All micelles possessed spherical morphology. The aggregation number,
      structure, and electrophoretic mobility of micelles changed in a jumplike manner
      near beta ~ 0.6-0.75. Below and above this region, micelle characteristics were
      constant or insignificantly changed upon beta. Theoretical dependencies for
      micelle aggregation number, corona dimensions, and fraction of small counterions
      outside corona versus beta were derived via minimization the micelle free energy,
      taking into account surface, volume, electrostatic, and elastic contributions of
      chain units and translational entropy of mobile counterions. Theoretical
      estimations also point onto a sharp structural transition at a certain corona
      composition. The abrupt reorganization of micelle structure at beta ~ 0.6-0.75
      entails dramatic changes in micelle dispersion stability in the presence of NaCl
      or in the presence of oppositely charged polymeric (sodium polymethacrylate) or
      amphiphilic (sodium dodecyl sulfate) complexing agents.

PMID- 23137285
TI  - A Kelch motif-containing serine/threonine protein phosphatase determines the
      large grain QTL trait in rice.
AB  - A thorough understanding of the genetic basis of rice grain traits is critical
      for the improvement of rice (Oryza sativa L.) varieties. In this study, we
      generated an F2 population by crossing the large-grain japonica cultivar CW23
      with Peiai 64 (PA64), an elite indica small-grain cultivar. Using QTL analysis,
      17 QTLs for five grain traits were detected on four different chromosomes. Eight
      of the QTLs were newly-identified in this study. In particular, qGL3-1, a newly
      identified grain length QTL with the highest LOD value and largest phenotypic
      variation, was fine-mapped to the 17 kb region of chromosome 3. A
      serine/threonine protein phosphatase gene encoding a repeat domain containing two
      Kelch motifs was identified as the unique candidate gene corresponding to this
      QTL. A comparison of PA64 and CW23 sequences revealed a single nucleotide
      substitution (C->A) at position 1092 in exon 10, resulting in replacement of Asp
      (D) in PA64 with Glu (E) in CW23 for the 364(th) amino acid. This variation is
      located at the D position of the conserved sequence motif AVLDT of the Kelch
      repeat. Genetic analysis of a near-isogenic line (NIL) for qGL3-1 revealed that
      the allele qGL3-1 from CW23 has an additive or partly dominant effect, and is
      suitable for use in molecular marker-assisted selection.

PMID- 23137287
TI  - Virological response for recurrent hepatitis C improves long-term survival in
      liver transplant recipients.
AB  - Recurrent hepatitis C virus (HCV) infection occurs universally and is regarded as
      a major cause of mortality after liver transplantation (LT) for HCV-related end
      stage liver disease. We conducted this large, single-center, retrospective study
      to ascertain the long-term impact of virological response to treatment of
      recurrent hepatitis C on survival of LT recipients. From August 1987 to October
      2011, 285 patients have received interferon-based antiviral therapy for recurrent
      hepatitis C. Of these 285, 245 patients were enrolled in this study. One hundred
      and twenty-six patients (51.4%) achieved sustained virological response (SVR).
      Relapsers (undetectable HCV-RNA at end of treatment, becoming positive afterward)
      comprised 9.0% (22/245), and nonresponse (NR; never achieving undetectable HCV
      RNA) 39.6% (97/245). The median follow-up after completion of antiviral treatment
      was 2081 days. Using Kaplan-Meier method, patients who achieved SVR were shown to
      have significantly better 5-year patient survival (95.2%) than the NR group
      (49.9%) (P < 0.001), and a trend toward better 5-year survival than relapsers
      (87.5%) (P = 0.14); relapsers had a significantly longer survival than NR group
      (P = 0.005). When compared with NR, SVR and relapse appeared to be significant
      predictors of better survival, independent of underlying characteristics. In
      conclusion, virological response, especially SVR, translates into markedly
      improved long-term patient outcomes in patients transplanted for hepatitis C.

PMID- 23137286
TI  - Trends in the prevalence of smoking in Portugal: a systematic review.
AB  - BACKGROUND: Understanding the dynamics of smoking at the population level is
      essential for the planning and evaluation of prevention and control measures. We
      aimed to describe trends in the prevalence of smoking in Portuguese adults by
      sex, age-group and birth cohort. METHODS: PubMed was searched from inception up
      to 2011. Linear regression was used to assess differences in prevalence estimates
      according to the type of population sampled, and to estimate time trends of
      smoking prevalence considering only the results of studies on nationally
      representative samples of the general population. RESULTS: Thirty eligible
      studies were identified. There were statistically significant differences in the
      prevalence estimates according to the types of population sampled in the original
      studies. Between 1987 and 2008, the prevalence of smoking increased significantly
      among women aged <= 70 years; the steepest increase was observed in those aged 31
      50 and 51-70 years (from 4.6% and 0.1% in 1988, respectively, to 16.4% and 4.5%
      in 2008, respectively). The prevalence of smoking increased in all birth cohorts,
      except for those born before 1926. In the same period, among men, smoking
      decreased in all age-groups, with steepest declines in those aged <= 30 years
      (from 41.8% in 1988 to 28.8% in 2008) and those aged >= 71 years (from 15.1% in
      1988 to 4.6% in 2008). The prevalence of smoking declined among men of all birth
      cohorts. CONCLUSIONS: This study provides robust evidence to place Portuguese
      women at stage II and men at the later stages of the tobacco epidemic.

PMID- 23137288
TI  - Greater night-to-night variability in sleep discrepancy among older adults with a
      sleep complaint compared to noncomplaining older adults.
AB  - Research in younger adults suggests sleep discrepancy (objective/subjective
      measurement difference) is a consistent pattern that primarily occurs within
      individuals with insomnia. To examine whether older adults exhibit a similar
      pattern, this study compared night-to-night inconsistency in sleep discrepancy
      between older adults with and without sleep complaints. Older adults (N = 103;
      mean age = 72.81, SD = 7.12) wore an Actiwatch-L(r) (24 hr per day) and
      concurrently completed sleep diaries for 14 days. Sleep discrepancy = diary
      (sleep onset latency [SOL] or wake [time] after sleep onset [WASO]) - actigraphy
      (SOL or WASO). Both groups exhibited sleep discrepancy, but complainers exhibited
      significantly more night-to-night variability. Sleep discrepancy was a variable
      behavior that was not limited to insomnia, but instead manifested by degree
      throughout our older sample. Greater attention to variability in sleep research
      and clinical practice is warranted.

PMID- 23137289
TI  - The association between body mass index and health-related quality of life:
      influence of ethnicity on this relationship.
AB  - AIMS: The association between obesity and a poorer health-related quality of life
      (HRQL) has previously been explored. The influence of ethnicity on this
      relationship has less frequently been considered. We aimed to explore the
      relationship between body mass index (BMI) and HRQL in a mixed population of
      White European (WE) and South Asian (SA) ethnicity. METHODS: Cross-sectional data
      were analysed (n = 4989, 16% SA) from a population-based diabetes screening
      study. BMI categories were based on ethnic-specific cut-points. HRQL was
      categorized low (<0.848) or high (>=0.848) according to the median EQ5D score.
      Logistic regression was used to examine the relationship between BMI and HRQL.
      Interaction analysis was conducted to determine the effect of ethnicity. RESULTS:
      Overweight (OR = 1.22, 95% CI: 1.10-1.41, p < 0.001) and obese people (OR = 1.81,
      95% CI: 1.56-2.10, p < 0.001) had increased odds of having a low HRQL compared to
      normal weight people. After adjusting for potential confounders, age, gender,
      ethnicity, deprivation score, fruit and vegetable intake, physical activity,
      cardiovascular disease, chronic kidney disease and smoking, this association was
      strengthened further. However, for obese people, SA ethnicity significantly
      reduced the risk of having a low HRQL when compared to WEs (adjusted OR = 0.58,
      95% CI: 0.34-0.97). CONCLUSIONS: Our findings provide further evidence of an
      association between increasing BMI and low HRQL but suggest that SA ethnicity
      modifies this relationship. These results could have important health
      implications and are a basis for further research.

PMID- 23137290
TI  - Tissue dyslipidemia in Salmonella-infected rats treated with amoxillin and
      pefloxacin.
AB  - BACKGROUND: This study investigated the effects of salmonella infection and its
      chemotherapy on lipid metabolism in tissues of rats infected orally with
      Salmonella typhimurium and treated intraperitoneally with pefloxacin and
      amoxillin. METHODS: Animals were infected with Salmonella enterica serovar
      Typhimurium strain TA 98. After salmonellosis was confirmed, they were divided
      into 7 groups of 5 animals each. While one group served as infected control
      group, three groups were treated with amoxillin (7.14 mg/kg body weight, 8
      hourly) and the remaining three groups with pefloxacin (5.71 mg/kg body weight,
      12 hourly) for 5 and 10 days respectively. Uninfected control animals received
      0.1 ml of vehicle. Rats were sacrificed 24h after 5 and 10 days of antibiotic
      treatment and 5 days after discontinuation of antibiotic treatment. Their
      corresponding controls were also sacrificed at the same time point. Blood and
      tissue lipids were then evaluated. RESULTS: Salmonella infection resulted in
      dyslipidemia characterised by increased concentrations of free fatty acids (FFA)
      in plasma and erythrocyte, as well as enhanced cholesterogenesis,
      hypertriglyceridemia and phospholipidosis in plasma, low density lipoprotein-very
      low density lipoprotein (LDL-VLDL), erythrocytes, erythrocyte ghost and the
      organs. The antibiotics reversed the dyslipidemia but not totally. A significant
      correlation was observed between fecal bacterial load and plasma cholesterol
      (r=0.456, p<0.01), plasma triacyglycerols (r=0.485, p<0.01), plasma phospholipid
      (r=0.414, p<0.05), plasma free fatty acids (r=0.485, p<0.01), liver phospholipid
      (r=0.459, p<0.01) and brain phospholipid (r=0.343, p<0.05). CONCLUSION: The
      findings of this study suggest that salmonella infection in rats and its therapy
      with pefloxacin and amoxillin perturb lipid metabolism and this perturbation is
      characterised by cholesterogenesis.

PMID- 23137291
TI  - High-throughput novel microsatellite marker of faba bean via next generation
      sequencing.
AB  - BACKGROUND: Faba bean (Vicia faba L.) is an important food legume crop, grown for
      human consumption globally including in China, Turkey, Egypt and Ethiopia.
      Although genetic gain has been made through conventional selection and breeding
      efforts, this could be substantially improved through the application of
      molecular methods. For this, a set of reliable molecular markers representative
      of the entire genome is required. RESULTS: A library with 125,559 putative SSR
      sequences was constructed and characterized for repeat type and length from a
      mixed genome of 247 spring and winter sown faba bean genotypes using 454
      sequencing. A suit of 28,503 primer pair sequences were designed and 150 were
      randomly selected for validation. Of these, 94 produced reproducible amplicons
      that were polymorphic among 32 faba bean genotypes selected from diverse
      geographical locations. The number of alleles per locus ranged from 2 to 8, the
      expected heterozygocities ranged from 0.0000 to 1.0000, and the observed
      heterozygosities ranged from 0.0908 to 0.8410. The validation by UPGMA cluster
      analysis of 32 genotypes based on Nei's genetic distance, showed high quality and
      effectiveness of those novel SSR markers developed via next generation sequencing
      technology. CONCLUSIONS: Large scale SSR marker development was successfully
      achieved using next generation sequencing of the V. faba genome. These novel
      markers are valuable for constructing genetic linkage maps, future QTL mapping,
      and marker-assisted trait selection in faba bean breeding efforts.

PMID- 23137292
TI  - Ex vivo antimicrobial efficacy of the EndoVac system plus photodynamic therapy
      associated with calcium hydroxide against intracanal Enterococcus faecalis.
AB  - AIM: To evaluate the ex vivo efficacy of the EndoVac system and photodynamic
      treatment (PDT) as adjuncts to chemomechanical debridement associated with
      calcium hydroxide (CaOH2 ) in reducing the levels of intracanal Enterococcus
      faecalis. METHODOLOGY: One hundred and twenty-five sterile premolar teeth were
      conventionally accessed, prepared and then contaminated with E. faecalis (ATCC
      29212) for 30 days. Teeth were randomly divided into 4 groups: Control
      (chemomechanical debridement with conventional irrigation); Endovac
      (chemomechanical debridement with EndoVac system); PDT (chemomechanical
      debridement with conventional irrigation and PDT) and Endovac+PDT
      (chemomechanical debridement with EndoVac and PDT). The irrigants used in all
      groups were 5.25% sodium hypochlorite and 17% EDTA. After treatment, an
      intracanal dressing (CaOH2 ) was applied in all canals for 7 days. Samples were
      obtained before (T1) and after the therapeutic procedures (T2) and, after
      intracanal medication (T3), plated onto BHI media and incubated (37  degrees C,
      48 h) to determine the colony-forming units (CFU mL(-1) ). RESULTS: The overall
      mean cell counts (CFU mL(-1) ) of E. faecalis were high at the initial
      contamination (T1). A significant reduction (P < 0.05) of E. faecalis mean counts
      was observed in all groups from baseline (T1) to both post-therapy samplings (T2
      and T3); no differences amongst the groups were detected. No significant change
      in bacterial counts from T2 to T3 was detected. CONCLUSION: The adjunctive use of
      the EndoVac system and the photodynamic treatment, in combination or not, was as
      effective as the conventional chemomechanical debridement associated with CaOH2
      on reducing the counts of intracanal E. faecalis.

PMID- 23137293
TI  - On-chip alternating current electrophoresis in supported lipid bilayer membranes.
AB  - By forming lipid bilayers within SU8 patterns, between interdigitated electrodes,
      we have demonstrated that it is possible to manipulate charged membrane
      components using low applied voltages over relatively short time scales. Two
      distinct patterns were studied: a nested "fish trap" which served as a molecular
      trap, and a diffusion aided Brownian ratchet which operated as a molecular pump.
      By reducing the size of the structures we have demonstrated that large applied
      fields (>200 V/cm) can be achieved on-chip, using low applied potentials (<13 V).
      By using ac fields applied orthogonal to the direction of desired motion, the
      molecular pumps provide a voltage independent method for moving charged
      components within lipid membranes over large distances. The reduced scale of the
      trap structures compared to those previously used in our laboratory has led to
      over a 10-fold decrease in the operational time require for charge build-up, from
      16 h down to 1.5 h. The observed benefits of scaling means that these systems
      should be suitable for the on-chip separation and manipulation of charged species
      within supported lipid membranes.

PMID- 23137294
TI  - Performance of immunological response in predicting virological failure.
AB  - In HIV-infected individuals on antiretroviral therapy (ART), the decision on when
      to switch from first-line to second-line therapy is dictated by treatment
      failure, and this can be measured in three ways: clinically, immunologically, and
      virologically. While viral load (VL) decreases and CD4 cell increases typically
      occur together after starting ART, discordant responses may be seen. Hence the
      current study was designed to determine the immunological and virological
      response to ART and to evaluate the utility of immunological response to predict
      virological failure. All treatment-naive HIV-positive individuals aged >18 years
      who were eligible for ART were enrolled and assessed at baseline, 6 months, and
      12 months clinically and by CD4 cell count and viral load estimations. The
      patients were categorized as showing concordant favorable (CF), immunological
      only (IO), virological only (VO), and concordant unfavorable responses (CU). The
      efficiency of immunological failure to predict virological failure was analyzed
      across various levels of virological failure (VL>50, >500, and >5,000 copies/ml).
      At 6 months, 87(79.81%), 7(5.5%), 13 (11.92%), and 2 (1.83%) patients and at 12
      months 61(69.3%), 9(10.2%), 16 (18.2%), and 2 (2.3%) patients had CF, IO, VO, and
      CU responses, respectively. Immunological failure criteria had a very low
      sensitivity (11.1-40%) and positive predictive value (8.3-25%) to predict
      virological failure. Immunological criteria do not accurately predict virological
      failure resulting in significant misclassification of therapeutic responses.
      There is an urgent need for inclusion of viral load testing in the initiation and
      monitoring of ART.

PMID- 23137295
TI  - A top-down approach impedes the use of theory? Interprofessional educational
      leaders' approaches to curriculum development and the use of learning theory.
AB  - International policy has emphasized the development of interprofessional
      education (IPE) to reinforce interprofessional practice. This study explored the
      extent to which IPE initiatives in the UK are based on sound theoretical
      frameworks. Findings from semi-structured interviews with lead IPE curriculum
      developers at eight higher education institutions are presented which identified
      curriculum developers' developmental approaches to IPE. The findings reveal a
      notable lack of explicit theoretical basis for models of IPE. In many cases,
      senior managers determined the institutional approach to IPE which academic staff
      then needed to deliver. Curriculum developers reported adopting a largely
      practical approach to IPE curriculum development. However, questioning that
      focused on learning and teaching methods revealed that a range of learning
      theories was used implicitly. The significance of these findings is discussed
      with recommendations to inform future curriculum development of IPE initiatives.

PMID- 23137296
TI  - Cell-selective biological activity of rhodium metalloinsertors correlates with
      subcellular localization.
AB  - Deficiencies in the mismatch repair (MMR) pathway are associated with several
      types of cancers, as well as resistance to commonly used chemotherapeutics.
      Rhodium metalloinsertors have been found to bind DNA mismatches with high
      affinity and specificity in vitro, and also exhibit cell-selective cytotoxicity,
      targeting MMR-deficient cells over MMR-proficient cells. Ten distinct
      metalloinsertors with varying lipophilicities have been synthesized and their
      mismatch binding affinities and biological activities determined. Although DNA
      photocleavage experiments demonstrate that their binding affinities are quite
      similar, their cell-selective antiproliferative and cytotoxic activities vary
      significantly. Inductively coupled plasma mass spectrometry (ICP-MS) experiments
      have uncovered a relationship between the subcellular distribution of these
      metalloinsertors and their biological activities. Specifically, we find that all
      of our metalloinsertors localize in the nucleus at sufficient concentrations for
      binding to DNA mismatches. However, the metalloinsertors with high rhodium
      localization in the mitochondria show toxicity that is not selective for MMR
      deficient cells, whereas metalloinsertors with less mitochondrial rhodium show
      activity that is highly selective for MMR-deficient versus proficient cells. This
      work supports the notion that specific targeting of the metalloinsertors to
      nuclear DNA gives rise to their cell-selective cytotoxic and antiproliferative
      activities. The selectivity in cellular targeting depends upon binding to
      mismatches in genomic DNA.

PMID- 23137298
TI  - Understanding the interaction of block copolymers with DMPC lipid bilayer using
      coarse-grained molecular dynamics simulations.
AB  - In this paper, we present a computational model of the adsorption and percolation
      mechanism of poloxamers (poly(ethylene oxide) (PEO) and poly(propylene oxide)
      (PPO) triblock copolymers) across a 1,2-dimyristoyl-sn-glycero-3-phosphocholine
      (DMPC) lipid bilayer. A coarse-grained model was used to cope with the long time
      scale of the percolation process. The simulations have provided details of the
      interaction mechanism of Pluronics with lipid bilayer. In particular, the results
      have shown that polymer chains containing a PPO block with a length comparable to
      the DMPC bilayer thickness, such as P85, tends to percolate across the lipid
      bilayer. On the contrary, Pluronics with a shorter PPO chain, such as L64 and
      F38, insert partially into the membrane with the PPO block part while the PEO
      blocks remain in water on one side of the lipid bilayer. The percolation of the
      polymers into the lipid tail groups reduces the membrane thickness and increases
      the area per lipid. These effects are more evident for P85 than L64 or F38. Our
      findings are qualitatively in good agreement with published small-angle X-ray
      scattering experiments that have evidenced a thinning effect of Pluronics on the
      lipid bilayer as well as the role of the length of the PPO block on the
      permeation process of the polymer through the lipid bilayer. Our theoretical
      results complement the experimental data with a detailed structural and dynamic
      model of poloxamers at the interface and inside the lipid bilayer.

PMID- 23137297
TI  - The folded and disordered domains of human ribosomal protein SA have both
      idiosyncratic and shared functions as membrane receptors.
AB  - The human RPSA [ribosomal protein SA; also known as LamR1(laminin receptor 1)]
      belongs to the ribosome but is also a membrane receptor for laminin, growth
      factors, prion, pathogens and the anticarcinogen EGCG (epigallocatechin-gallate).
      It contributes to the crossing of the blood-brain barrier by neurotropic viruses
      and bacteria, and is a biomarker of metastasis. RPSA includes an N-terminal
      domain, which is folded and homologous to the prokaryotic RPS2, and a C-terminal
      extension, which is intrinsically disordered and conserved in vertebrates. We
      used recombinant derivatives of RPSA and its N- and C-domains to quantify its
      interactions with ligands by in-vitro immunochemical and spectrofluorimetric
      methods. Both N- and C-domains bound laminin with K(D) (dissociation constants)
      of 300 nM. Heparin bound only to the N-domain and competed for binding to laminin
      with the negatively charged C-domain, which therefore mimicked heparin. EGCG
      bound only to the N-domain with a K(D) of 100 nM. Domain 3 of the envelope
      protein from yellow fever virus and serotypes-1 and -2 of dengue virus bound
      preferentially to the C-domain whereas that from West Nile virus bound only to
      the N-domain. Our quantitative in-vitro approach should help clarify the
      mechanisms of action of RPSA, and ultimately fight against cancer and infectious
      agents.

PMID- 23137299
TI  - Hybridization of Southern Hemisphere blue whale subspecies and a sympatric area
      off Antarctica: impacts of whaling or climate change?
AB  - Understanding the degree of genetic exchange between subspecies and populations
      is vital for the appropriate management of endangered species. Blue whales
      (Balaenoptera musculus) have two recognized Southern Hemisphere subspecies that
      show differences in geographic distribution, morphology, vocalizations and
      genetics. During the austral summer feeding season, the Antarctic blue whale (B.
      m. intermedia) is found in polar waters and the pygmy blue whale (B. m.
      brevicauda) in temperate waters. Here, we genetically analyzed samples collected
      during the feeding season to report on several cases of hybridization between the
      two recognized blue whale Southern Hemisphere subspecies in a previously
      unconfirmed sympatric area off Antarctica. This means the pygmy blue whales using
      waters off Antarctica may migrate and then breed during the austral winter with
      the Antarctic subspecies. Alternatively, the subspecies may interbreed off
      Antarctica outside the expected austral winter breeding season. The genetically
      estimated recent migration rates from the pygmy to Antarctic subspecies were
      greater than estimates of evolutionary migration rates and previous estimates
      based on morphology of whaling catches. This discrepancy may be due to
      differences in the methods or an increase in the proportion of pygmy blue whales
      off Antarctica within the last four decades. Potential causes for the latter are
      whaling, anthropogenic climate change or a combination of these and may have led
      to hybridization between the subspecies. Our findings challenge the current
      knowledge about the breeding behaviour of the world's largest animal and provide
      key information that can be incorporated into management and conservation
      practices for this endangered species.

PMID- 23137300
TI  - The effect of silymarin (Silybum marianum) on human skin fibroblasts in an in
      vitro wound healing model.
AB  - CONTEXT: Silymarin, a flavonolignan from Silybum marianum (L.) Gaertn.
      (Asteraceae), has been reported to have antioxidant and anti-inflammatory
      properties. Therefore, it may be worthwhile to study the effect of silymarin on
      wound healing. OBJECTIVE: To evaluate the effect of silymarin on human fibroblast
      cells in an in vitro model of wound healing. MATERIALS AND METHODS: Human
      fibroblast cells were treated with different concentrations (4.5, 9, 18, 36
      ug/mL) of silymarin. The effects of silymarin on cell viability, proliferation,
      collagen synthesis, and expression of cyclooxygenase-2 (COX-2) and inducible
      nitric oxide synthetase (iNOS) were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide, 5-bromo-2'-deoxy-uridine, hydroxyproline analysis
      and real-time PCR, respectively. The effect of silymarin on cellular antioxidant
      status was determined by protection against hydrogen peroxide (H2O2)-induced cell
      injury and free radical scavenging activity (ABTS assay) of the cells. RESULTS:
      Results of the present study indicate that pretreatment of fibroblast cells with
      silymarin significantly protected cells against H2O2-induced injury (p < 0.05).
      After an 18 h treatment of cells with 36 ug/mL silymarin, total antioxidant
      capacity of cells significantly increased (p < 0.05). Furthermore, pretreatment
      of human fibroblast cells with silymarin significantly inhibited
      lipopolysaccharide (LPS)-induced COX-2 mRNA expression (p < 0.001). There was no
      significant difference in fibroblast proliferation and collagen synthesis between
      treatment and control groups (p > 0.05). DISCUSSION AND CONCLUSION: Silymarin may
      be useful as a therapeutic agent for the treatment of cutaneous wounds through
      its antioxidation and anti-inflammation effects.

PMID- 23137301
TI  - Association of subgingival colonization of Candida albicans and other yeasts with
      severity of chronic periodontitis.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study is to analyze the relationship
      between the subgingival colonization by Candida albicans and other yeasts with
      the severity of chronic periodontitis (CP). MATERIAL AND METHODS: After sample
      size calculation, 40 patients with CP and 20 healthy subjects (HS) were included
      in the study. Cases of slight-moderate (MCP, n = 23) and severe CP (SCP, n = 17)
      were defined according to the Centers for Disease Control/American Association of
      Periodontology classification. Subgingival samples were acquired using sterile
      paper-points from the sulcus or the deepest periodontal pocket of each healthy
      and subject with CP, respectively, and were cultured aerobically on three
      selective media. Yeast colonies that grew on the surface of plates were later
      identified by biochemical reactions. Statistical tests were used to analyze the
      association between subgingival yeast colonization (number of yeast-positive
      individuals and colony forming units (CFU) per subject) and periodontal disease
      status, considering statistical significance when P < 0.05. RESULTS: Although
      several yeast species were found (C. parapisilosis, Rhodotorula sp., C.
      dubliniensis and C. tropicalis), only C. albicans was present in all the patients
      with yeast-positive CP. Twelve patients (30%) with CP presented yeasts in the
      subgingival biofilm while only three patients (15%) in the HS group were positive
      for these microorganisms. No statistical difference was found between the CP and
      HS groups (P = 0.084). However, when the CP group was divided on the basis of
      severity, statistical differences were observed between the SCP and MCP groups
      (47% vs. 17%, P = 0.043), and between the SCP and HS groups (47% vs. 15%, P =
      0.033). No statistical difference was observed between the MCP and HS groups (17%
      vs. 15%, P = 0.832). High densities of yeasts were found only in patients with
      MCP and SCP (mean and range 61.25 (0-100) CFU/plate and mean and range 51 (0-101)
      CFU/plate, respectively). CONCLUSION: In this group of patients, subgingival
      colonization of some yeasts, especially C. albicans, was associated with the
      severity of CP.

PMID- 23137302
TI  - Prolonging the duration of preventing bacterial adhesion of nanosilver-containing
      polymer films through hydrophobicity.
AB  - A superhydrophobic coating composed of silver nanoparticles was developed on
      copper from fluorinated multilayered polyelectrolyte films to examine its
      performance in preventing microbial adhesion. Antibacterial and antibiofouling
      experiments for this novel coating were conducted with SRB. From the disk
      diffusion tests (for 48 h), it was found that, compared to the traditional
      coating composed of nanosilver, this novel coating significantly improved
      antibacterial performance and long-term effectiveness. The oxidation states of
      the immobilized silver in polyelectrolyte multilayer films were investigated with
      X-ray photoelectron spectroscopy (XPS), and the stability of the immobilized
      silver was evaluated through a leaching test. It was found that if silver was
      exposed to aqueous environments some ionic silver species would be produced and
      released. The ion release kinetics showed that the duration of sustained release
      of antibacterial Ag ions from the novel coatings was prolonged, which was why
      they had more long-term antibacterial performance.

PMID- 23137303
TI  - Design, synthesis, and pharmacological evaluation of monocyclic pyrimidinones as
      novel inhibitors of PDE5.
AB  - Cyclic nucleotide phosphodiesterase type 5 (PDE5) is a prime drug target for
      treating the diseases associated with a lower level of the cyclic guanosine
      monophosphate (cGMP), which is a specific substrate for PDE5 hydrolysis. Here we
      report a series of novel PDE5 inhibitors with the new scaffold of the monocyclic
      pyrimidin-4(3H)-one ring developed using the structure-based discovery strategy.
      In total, 37 derivatives of the pyrimidin-4(3H)-ones, were designed, synthesized,
      and evaluated for their inhibitory activities to PDE5, resulting in 25 compounds
      with IC50 ranging from 1 to 100 nM and 11 compounds with IC50 ranging from 1 to
      10 nM. Compound 5, 5,6-diethyl-2-[2-n-propoxy-5-(4-methyl-1
      piperazinylsulfonyl)phenyl]pyrimid-4(3H)-one, the most potent compound, has an
      excellent IC50 (1.6 nM) in vitro and a good efficacy in a rat model of erection.
      It thus provides a potential candidate for the further development into a new
      drug targeting PDE5.

PMID- 23137304
TI  - Modelling strategic interventions in a population with a total fertility rate of
      8.3: a cross-sectional study of Idjwi Island, DRC.
AB  - BACKGROUND: Idjwi, an island of approximately 220,000 people, is located in
      eastern DRC and functions semi-autonomously under the governance of two kings
      (mwamis). At more than 8 live births per woman, Idjwi has one of the highest
      total fertility rates (TFRs) in the world. Rapid population growth has led to
      widespread environmental degradation and food insecurity. Meanwhile family
      planning services are largely unavailable. METHODS: At the invitation of local
      leaders, we conducted a representative survey of 2,078 households in accordance
      with MEASURE DHS protocols, and performed ethnographic interviews and focus
      groups with key informants and vulnerable subpopulations. Modelling proximate
      determinates of fertility, we evaluated how the introduction of contraceptives
      and/or extended periods of breastfeeding could reduce the TFR. RESULTS: Over half
      of all women reported an unmet need for spacing or limiting births, and nearly
      70% named a specific modern method of contraception they would prefer to use;
      pills (25.4%) and injectables (26.5%) were most desired. We predicted that an
      increased length of breastfeeding (from 10 to 21 months) or an increase in
      contraceptive prevalence (from 1% to 30%), or a combination of both could reduce
      TFR on Idjwi to 6, the average desired number of children. Increasing
      contraceptive prevalence to 15% could reduce unmet need for contraception by 8%.
      CONCLUSIONS: To meet women's need and desire for fertility control, we recommend
      adding family planning services at health centers with NGO support, pursuing a
      community health worker program, promoting extended breastfeeding, and
      implementing programs to end sexual- and gender-based violence toward women.

PMID- 23137305
TI  - Association of carcinoid tumor and low grade glioma.
AB  - BACKGROUND: Lung carcinoid tumor and low grade glioma are two uncommon
      malignancies. PATIENTS AND METHODS: We report the case of 24-year-old man who
      presented with respiratory disease. Imaging investigations showed a right lung
      tumor and histological analysis confirmed a typical carcinoid tumor. As part of
      initial staging, brain MRI revealed an asymptomatic right frontal lesion. First,
      a right pulmonary lobectomy was performed without adjuvant treatment. In second
      time, brain tumorectomy was performed. Histological examination confirmed the
      diagnosis of low grade glioma (LGG). The patient remained in complete remission
      2.5 years after the initial diagnosis. RESULTS: This is the first case reporting
      the association between LGG and lung carcinoid tumor, while no association
      between LGG and a systemic tumor have been published to date. Association of lung
      carcinoid tumor with other malignant diseases has been reported but remained
      uncommon. Only minimal data support a potential molecular common origin.
      CONCLUSION: This exceptional association may be fortuitous. However, their
      concomitant diagnoses suggest a potential association between both rare diseases.
      A genetic susceptibility remains possible.

PMID- 23137306
TI  - Soluble CD30 correlates with clinical but not subclinical renal allograft
      rejection.
AB  - Soluble CD30 (sCD30) has been proposed as a promising noninvasive biomarker for
      clinical renal allograft rejection, but its diagnostic characteristics regarding
      detection of subclinical rejection have not been assessed. We investigated sCD30
      in 146 consecutive kidney allograft recipients under tacrolimus-mycophenolate
      based immunosuppression having 250 surveillance biopsies at 3 and 6 months as
      well as 52 indication biopsies within the first year post-transplant. Allograft
      histology results were classified as (i) acute Banff score zero or interstitial
      infiltrates only, (ii) tubulitis t1, (iii) tubulitis t2-3 and (iv) isolated
      vascular compartment inflammation. sCD30 correlated well with the extent of
      clinical (P < 0.0001), but not subclinical tubulointerstitial rejection (P =
      0.06). To determine diagnostic characteristics of sCD30, histological groups were
      assigned to two categories: no relevant inflammation (i.e. acute Banff score zero
      and interstitial infiltrates only) versus all other pathologies (tubulitis t1-3
      and isolated vascular compartment inflammation). For clinical allograft
      inflammation, AUC was 0.87 (sensitivity 89%, specificity 79%; P = 0.0006);
      however, for subclinical inflammation, AUC was only 0.59 (sensitivity 50%,
      specificity 69%; P = 0.47). In conclusion, sCD30 correlated with clinical, but
      not subclinical renal allograft rejection limiting its clinical utility as a
      noninvasive rejection screening biomarker in patients with stable allograft
      function receiving tacrolimus-mycophenolate-based immunosuppression.

PMID- 23137307
TI  - Role of ABO blood group as a prognostic factor in patients with spontaneous
      intracerebral hemorrhage.

PMID- 23137309
TI  - Immunogenomics for identification of disease resistance genes in pigs: a review
      focusing on Gram-negative bacilli.
AB  - Over the past years, infectious disease has caused enormous economic loss in pig
      industry. Among the pathogens, gram negative bacteria not only cause
      inflammation, but also cause different diseases and make the pigs more
      susceptible to virus infection. Vaccination, medication and elimination of sick
      pigs are major strategies of controlling disease. Genetic methods, such as
      selection of disease resistance in the pig, have not been widely used. Recently,
      the completion of the porcine whole genome sequencing has provided powerful tools
      to identify the genome regions that harboring genes controlling disease or
      immunity. Immunogenomics, which combines DNA variations, transcriptome, immune
      response, and QTL mapping data to illustrate the interactions between pathogen
      and host immune system, will be an effective genomics tool for identification of
      disease resistance genes in pigs. These genes will be potential targets for
      disease resistance in breeding programs. This paper reviewed the progress of
      disease resistance study in the pig focusing on Gram-negative bacilli. Major
      porcine Gram-negative bacilli and diseases, suggested candidate genes/pathways
      against porcine Gram-negative bacilli, and distributions of QTLs for immune
      capacity on pig chromosomes were summarized. Some tools for immunogenomics
      research were described. We conclude that integration of sequencing, whole genome
      associations, functional genomics studies, and immune response information is
      necessary to illustrate molecular mechanisms and key genes in disease resistance.

PMID- 23137310
TI  - Fibroblast growth factor signaling regulates neurogenesis at multiple stages in
      the embryonic olfactory epithelium.
AB  - Lifelong neurogenesis in the mouse olfactory epithelium (OE) is regulated by the
      response of stem/progenitor cells to local signals, but embryonic and adult OE
      progenitors appear to be quite different--with potentially different mechanisms
      of regulation. A recently identified progenitor unique to embryonic OE--the
      nestin+ radial glial-like progenitor--precedes some Mash1+ progenitors in the
      olfactory receptor neuron (ORN) lineage, which then gives rise to immediate
      neuronal precursors and immature ORNs. Neurogenic drive at each stage is governed
      largely by exogenous factors. Fibroblast growth factor 2 (FGF2) is believed to
      increase cell proliferation in both presumptive OE stem cells and immediate
      neuronal precursors in explants, but whether FGF2 directly acts on different
      target progenitors or stages in the embryonic OE is not known. Here we show that
      fibroblast growth factor receptor (FGFR)1 and FGFR2 are found in a variety of
      embryonic olfactory cells, including olfactory ensheathing cells and their
      precursors, and neuronal nestin+ and Mash1+ progenitors. Combining gain and loss
      of function for FGF2 activity in a novel in vitro clonal progenitor assay, we
      reveal that different colony phenotypes are formed by presumably different OE
      progenitors. FGF2 is essential for the survival and expansion of colony-forming
      cells of the OE, and also enhances the proliferation of embryonic Mash1+
      progenitors, leading to long-lived enhancement of neurogenesis. Our data suggest
      that distinct OE progenitors yield different in vitro phenotypes with different
      potentials, that colony-forming activity is profoundly altered by laminin and
      collagen, that multiple ORNs can be produced from single colony-forming
      progenitors, and demonstrate a broader progenitor range of FGF action in the
      embryonic OE than previously demonstrated.

PMID- 23137308
TI  - Comparative genomic analysis and phylogenetic position of Theileria equi.
AB  - BACKGROUND: Transmission of arthropod-borne apicomplexan parasites that cause
      disease and result in death or persistent infection represents a major challenge
      to global human and animal health. First described in 1901 as Piroplasma equi,
      this re-emergent apicomplexan parasite was renamed Babesia equi and subsequently
      Theileria equi, reflecting an uncertain taxonomy. Understanding mechanisms by
      which apicomplexan parasites evade immune or chemotherapeutic elimination is
      required for development of effective vaccines or chemotherapeutics. The
      continued risk of transmission of T. equi from clinically silent, persistently
      infected equids impedes the goal of returning the U. S. to non-endemic status.
      Therefore comparative genomic analysis of T. equi was undertaken to: 1) identify
      genes contributing to immune evasion and persistence in equid hosts, 2) identify
      genes involved in PBMC infection biology and 3) define the phylogenetic position
      of T. equi relative to sequenced apicomplexan parasites. RESULTS: The known
      immunodominant proteins, EMA1, 2 and 3 were discovered to belong to a ten member
      gene family with a mean amino acid identity, in pairwise comparisons, of 39%.
      Importantly, the amino acid diversity of EMAs is distributed throughout the
      length of the proteins. Eight of the EMA genes were simultaneously transcribed.
      As the agents that cause bovine theileriosis infect and transform host cell
      PBMCs, we confirmed that T. equi infects equine PBMCs, however, there is no
      evidence of host cell transformation. Indeed, a number of genes identified as
      potential manipulators of the host cell phenotype are absent from the T. equi
      genome. Comparative genomic analysis of T. equi revealed the phylogenetic
      positioning relative to seven apicomplexan parasites using deduced amino acid
      sequences from 150 genes placed it as a sister taxon to Theileria spp.
      CONCLUSIONS: The EMA family does not fit the paradigm for classical antigenic
      variation, and we propose a novel model describing the role of the EMA family in
      persistence. T. equi has lost the putative genes for host cell transformation, or
      the genes were acquired by T. parva and T. annulata after divergence from T.
      equi. Our analysis identified 50 genes that will be useful for definitive
      phylogenetic classification of T. equi and closely related organisms.

PMID- 23137311
TI  - Alexithymic and somatisation scores in patients with temporomandibular pain
      disorder correlate with deficits in facial emotion recognition.
AB  - Current studies suggest dysfunctional emotional processing as a key factor in the
      aetiology of temporomandibular disorder (TMD). Investigating facial emotion
      recognition (FER) may offer an elegant and reliable way to study emotional
      processing in patients with TMD. Twenty patients with TMD and the same number of
      age-, sex- and education-matched controls were measured with the Facially
      Expressed Emotion Labelling (FEEL) test, the 26-item Toronto Alexithymia Scale
      (TAS-26), the Screening for Somatoform Symptoms (SOMS-2a), the German Pain
      Questionnaire and the 21-item Hamilton Depression Rating Scale (HAMD). The
      patients had significantly lower Total FEEL Scores (P = 0.021) as compared to the
      controls, indicating a lower accuracy of FER. Furthermore, we were able to
      demonstrate significant group differences with respect to the following issues:
      patients were more alexithymic (P = 0.006), stated more somatoform symptoms (P <
      0.004) and had higher depressive scores in the HAMD (P < 0.003). The factors
      alexithymia and somatisation could explain 31% (adjusted 27%) of the variance of
      the FEEL Scores in the sample. The estimation of the standardised regression
      coefficients suggests an equivalent influence of TAS-26 and SOMS-2a on the FEEL
      Scores, whereas 'group' (patients versus healthy controls) and depressive
      symptoms did not contribute significantly to the model. Our findings highlight
      FER deficits in patients with TMD, which are partially explained by concomitant
      alexithymia and somatisation. As suggested previously, impaired FER in patients
      with TMD may further point to probable aetiological proximities between TMD and
      somatoform disorders.

PMID- 23137312
TI  - Bisphosphonates and their clinical implications in endodontic therapy.
AB  - This review gives an overview of the factors that may play a role in the
      development of osteonecrosis of the jaw in patients treated with bisphosphonates
      (BPs) and undergoing nonsurgical endodontic treatment as well as some
      recommendations for its prevention. BPs are a widely prescribed group of drugs
      for diverse bone diseases. The occasional but devastating adverse effect of these
      drugs has been described as bisphosphonate-related osteonecrosis of the jaw
      (BRONJ). As this condition is debilitating and difficult to treat, all efforts
      should be made to prevent its occurence in patients at risk. The main triggering
      event is considered to be dental extraction. Even though nonsurgical endodontic
      treatment appears to be a relatively safe procedure, care remains essential.
      After an overview of this class of drugs, the clinical presentation, epidemiology
      and pathogenesis of BRONJ, as well as the possible risk factors associated with
      its development after nonsurgical endodontic treatment will be described.
      Finally, several strategies will be proposed for the prevention of BRONJ during
      nonsurgical endodontic treatment.

PMID- 23137313
TI  - Associations between preschoolers' daytime and nighttime sleep parameters.
AB  - This article examined associations between preschoolers' daytime and nighttime
      sleep parameters. A total of 63 preschoolers (65% boys; age: M = 4.15, SD = 0.62)
      participated. Sleep was assessed via actigraphy for 4 days and nights. Results
      are among the first to demonstrate significant associations between sleep
      parameters (especially sleep quality indexes) examined actigraphically at home
      and in child care contexts. Findings indicate that poor sleep quality indexed by
      greater sleep activity and awakenings, as well as less efficient sleep, were
      associated across nighttime sleep at home and daytime sleep in child care.
      Understanding connections between sleep across contexts has important
      implications for child care providers and parents as they attempt to facilitate
      child sleep during a developmental period of rapidly changing sleep patterns.

PMID- 23137314
TI  - Remission of diabetes in patients with long-standing type 2 diabetes following
      placement of adjustable gastric band: a retrospective case control study.
AB  - Rates of remission in obese patients with long-standing type 2 diabetes (>2
      years), following an adjustable gastric band are unclear. We conducted a
      retrospective case-control study of patients (n = 89) matched for age and body
      mass index with non-surgical controls. Cases had a longer duration of diabetes
      (99 +/- 53 and 80 +/- 59 months, p < 0.05) and a lower HbA1c than controls (7.9
      +/- 1.6 vs. 8.5 +/- 1.9%, p < 0.05). At follow-up (median 105 weeks) cases had
      lost 16.8 +/- 13.5 kg and controls 1.7 +/- 8.9 kg (p < 0.001) and HbA1c decreased
      by 0.6-0.8% (p < 0.001 for time) with no difference between cases and controls.
      Diabetes resolution, defined by HbA1c less than 6.5% and taking no medications,
      occurred in 14 (16%) cases and 2 controls. This is in contrast to published
      outcomes of resolution of type 2 diabetes after bariatric surgery. We conclude
      that there is a clear need for randomized studies of the effect of gastric
      banding in patients with long-standing type 2 diabetes.

PMID- 23137315
TI  - Potential antitumour and pro-oxidative effects of (E)-methyl 2-(7-chloroquinolin
      4-ylthio)-3-(4-hydroxyphenyl) acrylate (QNACR).
AB  - CONTEXT: Characterization of the pro-oxidant activity of QNACR. OBJECTIVES:
      Reactive oxygen species (ROS) induce cellular damage and represent unique
      opportunities to kill malignant cells. In this study, we synthesized and
      evaluated the new compound, (E)-methyl 2-(7-chloroquinolin-4-ylthio)-3-(4
      hydroxyphenyl) acrylate (QNACR) as potential pro-oxidative agent against breast
      cancer. METHODS: Oxidative stress biomarkers such as ROS, thiobarbuturic acid
      reactive species (TBARs) and different antioxidant enzyme activities were
      determined in cell lysates. RESULTS: QNACR showed cytotoxic and more selective
      effects to tumour MCF7 cells (IC50 < 25 uM) compared to antitumour controls,
      inducing ROS and TBARs parallel to inhibitions of catalase (CAT), glucose-6
      phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH).
      Longer exposures to QNACR triggered adaptive effects increasing the overall
      activities of CAT, glutathione reductase, G6PDH and 6PGDH, but eventually the
      adaptation changes faded and cells died. CONCLUSION: QNACR led to remarkable
      modifications in the oxidative status of tumour cells, proposing this compound as
      potential alternative for antitumour therapy.

PMID- 23137316
TI  - Morphometric analysis of treatment effects of the Balters bionator in growing
      Class II patients.
AB  - OBJECTIVE: To investigate the effects of the standard (Class II) Balters bionator
      in growing patients with Class II malocclusion with mandibular retrusion by using
      morphometrics (thin-plate spline [TPS] analysis). MATERIALS AND METHODS: Thirty
      one Class II patients (17 male and 14 female) were treated with the Balters
      bionator (bionator group). Mean age at the start of treatment (T0) was 10.3
      years, while it was 13 years at the end of treatment (T1). Mean treatment time
      was 2 years and 2 months. The control group consisted of 22 subjects (14 male and
      8 female) with untreated Class II malocclusion. Mean age at T0 was 10.2 years,
      while it was 12.2 years at T1. The observation period lasted 2 years on average.
      TPS analysis evaluated statistical (permutation tests) differences in the
      craniofacial shape and size between the bionator and control groups. RESULTS:
      Through TPS analysis (deformation grids) the bionator group showed significant
      shape changes in the mandible that could be described as a mandibular forward and
      downward displacement. The control group showed no statistically significant
      differences in the correction of Class II malocclusion. CONCLUSIONS: Bionator
      appliance is able to induce significant mandibular shape changes that lead to the
      correction of Class II dentoskeletal disharmony.

PMID- 23137317
TI  - Gravity driven deterministic lateral displacement for particle separation in
      microfluidic devices.
AB  - We investigate the two-dimensional continuous size-based separation of suspended
      particles in gravity-driven deterministic lateral displacement (g-DLD) devices.
      The suspended particles are driven through a periodic array of cylindrical
      obstacles under the action of gravity. We perform experiments covering the entire
      range of forcing orientations with respect to the array of obstacles and identify
      specific forcing angles that would lead to vector separation, in which different
      particles migrate, on an average, in different directions. A simple model, based
      on the lateral displacement induced on the trajectory of a particle by
      irreversible particle-obstacle interactions, accurately predicts the dependence
      of the migration angle on the forcing direction. The results provide design
      guidance for the development of g-DLD devices. We observe directional locking,
      which strongly depends on the size of the particle and suggests that relatively
      small forcing angles are well suited for size-fractionation purposes. We
      demonstrate excellent separation resolution for a binary mixture of particles at
      relatively small forcing angles, that is, forcing angles that are close to but
      smaller than the first transition angle of the larger particles in the mixture.

PMID- 23137318
TI  - Interplay of electron hopping and bounded diffusion during charge transport in
      redox polymer electrodes.
AB  - Redox polymer electrodes (RPEs) have been prepared both by attachment of random
      copolymers of hydroxybutyl methacrylate and vinylferrocene (poly(HBMA-co-VF)) to
      carbon substrates by grafting either "to" or "from" the substrate surfaces, and
      by impregnation of porous carbon substrates with redox polymer gels of similar
      composition. An observed linear dependence of peak current on the square root of
      the applied voltage scan rate in cyclic voltammetry (CV) led to the conclusion
      that the rate controlling step in the redox process was the diffusive transfer of
      electrons through the redox polymer layer. The variation in the peak current with
      increasing concentration of the redox species in the polymer indicated that the
      electron transport transitioned from bounded diffusion to electron hopping. A
      modified form of the Blauch-Saveant equation for apparent diffusivity of
      electrons through a polymer film indicated that bounded diffusion was the
      dominant mechanism of electron transport in RPEs with un-cross-linked polymer
      chains at low concentrations of the redox species, but, as the concentration of
      the redox species increased, electron hopping became more dominant, and was the
      primary mode of electron diffusion above a certain concentration level of redox
      species. In the cross-linked polymer gels, bounded diffusion was limited because
      of the restricted mobility of the polymer chains. Electron hopping was the
      primary mode of electron diffusion in such systems at all concentrations of the
      redox species.

PMID- 23137319
TI  - Controversies in granzyme biology.
AB  - Granzymes (Grz) are a family of serine proteases found in the granules of
      cytotoxic lymphocytes and are emerging as an important group of proteins involved
      in immune function and surveillance. Grz have both cytotoxic and more recently
      reported non-cytotoxic roles, however these functions are still subject to
      thorough investigation. The significance of the cytotoxic and importantly the non
      cytotoxic roles of Grz will be discussed in this review, detailing accepted and
      controversial functions.

PMID- 23137320
TI  - Characterization of the major histocompatibility complex class I A alleles in
      cynomolgus macaques of Vietnamese origin.
AB  - Cynomolgus macaques (Macaca fascicularis, Mafa) have emerged as an important
      animal model for infectious disease and transplantation research. Extensive
      characterization of their major histocompatibility complex (MHC) polymorphism
      regions therefore becomes urgently required. In this study, we identified 41 MHC
      class I A nucleotide sequences in 34 unrelated cynomolgus macaques of Vietnamese
      origin farmed in Southern China, including eight novel Mafa-A sequences. We found
      two sequences with perfect identity and six sequences with close similarity to
      previously defined MHC class I alleles from other populations, especially from
      Indonesian-origin macaques. We also found three Vietnamese-origin cynomolgus
      macaque MHC class I sequences for which the predicted protein sequences identical
      throughout their B and F binding pockets to Mamu-A1*001:01 and Mamu-A3*13:03,
      respectively. This is important because Mamu-A1*001:01 and Mamu-A3*13:03 are
      associated with longer survival and lower set-point viral load in simian
      immunodeficiency virus (SIV)-infected rhesus monkeys. These findings have
      implications for the evolutionary history of Vietnamese-origin cynomolgus macaque
      as well as for the use of this model in SIV/SHIV (a virus combining parts of the
      HIV and SIV genomes) research.

PMID- 23137321
TI  - TNFA promoter alleles--frequencies and linkage with classical HLA genes in a
      South German Caucasian population.
AB  - The tumor necrosis factor alpha (TNFA) promoter region exhibits several
      polymorphisms, which have been hypothesized to influence gene expression, thereby
      associating positively or negatively with inflammatory conditions. Many studies
      have focused on single nucleotide polymorphisms (SNPs) taking not into account
      additive or inverse effects between different SNPs. We typed 1,021 healthy
      Caucasian volunteer stem cell donors for their TNFA promoter as well as their HLA
      A,-C,-B,-DRB1 loci. Using statistical methods, we reconstructed TNFA promoter
      alleles and analyzed their frequency and linkage with HLA genes. We show that the
      number of TNFA promoter alleles frequent enough to be analyzed in clinical
      studies is limited and that a strong linkage with classical HLA genes is present,
      especially for the extended HLA-haplotype HLA-A*01:01/HLA-C*07:01/HLA
      B*08:01/TNFA promoter allele 3/HLA*DRB1*03:01. Taking into account SNP frequency
      information, it is possible to quite accurately deduce TNFA promoter alleles by
      generic Sanger sequencing, obviating the need for elaborating allele-specific
      sequencing. This information may enable investigators to consider the complete
      TNFA regulatory region in a phase-separated manner in contrast to previous
      approaches examining only one or few isolated SNPs.

PMID- 23137322
TI  - Using HLA loci to inform ancestry and health in Polynesian and Maori populations.
AB  - Human leukocyte antigens (HLA) are important genetic markers of tissue identity
      and accurately reflect ancestral history. The work reported in this paper
      provides a detailed description of HLA polymorphism in Polynesian and Maori
      individuals in relation to other populations. Our study concerns HLA classes I
      and II antigens in Polynesian (N = 36) and Maori (N = 114) subjects genotyped at
      two digit resolution by New Zealand Blood Service Laboratory in Auckland using
      polymerase chain reaction-sequence specific oligonucleotide and PCR-SSP
      technologies. We have also compared our data with those from other Austronesian
      speaking Mongoloid and Papuan-speaking Australoid populations in order to test
      previously published account of the origin of Proto-Polynesians via gender
      biassed gene flow between these two ancestral populations. We use principal
      coordinate analysis for this purpose, arguing this approach to be superior to
      tree-based methods, because of factors associated with population history and
      admixture. Our data are in general agreement with earlier work and reflect
      received wisdom on the dual origin of Proto-Polynesians. They also show the way
      in which the genetic make-up of Polynesian and Maori subjects is changing due to
      intermarriage with Europeans.

PMID- 23137323
TI  - Limited SP17 expression within tumors diminishes its therapeutic potential.
AB  - In this study, we have investigated the expression of the tumor antigen sperm
      protein 17 (SP17) in a large panel of human cancers and compared it with the
      expression of two well-characterized families of tumor antigens, melanoma
      associated antigen-A (MAGE-A) and G antigen (GAGE). We found that SP17 was
      expressed in many cancer types with an overall frequency of 12%. SP17 was most
      frequently expressed in a different set of cancer types than MAGE-A and GAGE
      antigens and rarely overlapped with these proteins. Importantly, SP17 expression
      was limited to a small number of scattered cancer cells in most positive tumors
      in contrast to MAGE-A and GAGE proteins, which were homogenously expressed in
      large foci. Our results suggest that SP17 may not be an optimal target for cancer
      vaccines.

PMID- 23137324
TI  - Comprehensive and high-resolution typing of swine leukocyte antigen DQA from
      genomic DNA and determination of 25 new SLA class II haplotypes.
AB  - We previously reported the development of genomic-DNA-based high-resolution
      genotyping methods for SLA-DQB1 and DRB1. Here, we report the successful typing
      of SLA-DQA using similar methodological principles. We designed a method for
      comprehensive genotyping of SLA-DQA using intronic sequence information of SLA
      DQA exon 2 that we had obtained from 12 animals with different SLA-DQB1
      genotypes. We expanded our typing to 76 selected animals with diverse DQB1 and
      DRB1 genotypes, 140 random animals from 7 pig breeds, and 3 wild boars. This
      resulted in the identification of 17 DQA alleles with 49 genotypes. Two new
      alleles were identified from wild boars. Combine with SLA-DQB1, and DRB1 typing
      results, we identified 34 SLA class II haplotypes including 25 that were
      previously unreported.

PMID- 23137325
TI  - Characterization of three novel HLA alleles with silent nucleotide substitutions.
AB  - Characterization of the novel HLA alleles B*35:11:03, B*42:01:03, and B*51:01:35
      is described.

PMID- 23137326
TI  - A novel HLA-A*66 allele, A*66:07.
AB  - HLA-A*66:07 allele differs from HLA-A*66:01 by an amino acid exchange at position
      165.

PMID- 23137327
TI  - Identification of a new allele HLA-B*40:213 by polymerase chain reaction sequence
      based typing in a Chinese patient suffering from chloroma.
AB  - This new HLA-B allele differs from the closest allele B*40:01:01 by two
      nucleotide changes at codons 102 and 267.

PMID- 23137328
TI  - Sequencing of the new HLA-B*44:150 allele suggests recombination between
      B*44:02:01:01 and B*07:02:01 alleles.
AB  - B*44:150 was identical to B*44:02:01:01 except at the 3'-end region of exon 3,
      where a B*07-specific sequence was identified.

PMID- 23137329
TI  - Nomenclature for factors of the HLA system, update July 2012.

PMID- 23137330
TI  - Nomenclature for factors of the HLA system, update August 2012.

PMID- 23137331
TI  - Nomenclature for factors of the HLA system, update September 2012.

PMID- 23137332
TI  - The impact of prolonged violent video-gaming on adolescent sleep: an experimental
      study.
AB  - Video-gaming is an increasingly prevalent activity among children and adolescents
      that is known to influence several areas of emotional, cognitive and behavioural
      functioning. Currently there is insufficient experimental evidence about how
      extended video-game play may affect adolescents' sleep. The aim of this study was
      to investigate the short-term impact of adolescents' prolonged exposure to
      violent video-gaming on sleep. Seventeen male adolescents (mean age = 16 +/- 1
      years) with no current sleep difficulties played a novel, fast-paced, violent
      video-game (50 or 150 min) before their usual bedtime on two different testing
      nights in a sleep laboratory. Objective (polysomnography-measured sleep and heart
      rate) and subjective (single-night sleep diary) measures were obtained to assess
      the arousing effects of prolonged gaming. Compared with regular gaming, prolonged
      gaming produced decreases in objective sleep efficiency (by 7 +/- 2%, falling
      below 85%) and total sleep time (by 27 +/- 12 min) that was contributed by a near
      moderate reduction in rapid eye movement sleep (Cohen's d = 0.48). Subjective
      sleep-onset latency significantly increased by 17 +/- 8 min, and there was a
      moderate reduction in self-reported sleep quality after prolonged gaming (Cohen's
      d = 0.53). Heart rate did not differ significantly between video-gaming
      conditions during pre-sleep game-play or the sleep-onset phase. Results provide
      evidence that prolonged video-gaming may cause clinically significant disruption
      to adolescent sleep, even when sleep after video-gaming is initiated at normal
      bedtime. However, physiological arousal may not necessarily be the mechanism by
      which technology use affects sleep.

PMID- 23137333
TI  - Diagnostic accuracy of diffusion-weighted imaging with conventional MR imaging
      for differentiating complex solid and cystic ovarian tumors at 1.5T.
AB  - BACKGROUND: Preoperative characterization of complex solid and cystic adnexal
      masses is crucial for informing patients about possible surgical strategies. Our
      study aims to determine the usefulness of apparent diffusion coefficients (ADC)
      for characterizing complex solid and cystic adnexal masses. METHODS: One-hundred
      and 91 patients underwent diffusion-weighted (DW) magnetic resonance (MR) imaging
      of 202 ovarian masses. The mean ADC value of the solid components was measured
      and assessed for each ovarian mass. Differences in ADC between ovarian masses
      were tested using the Student's t-test. The receiver operating characteristic
      (ROC) was used to assess the ability of ADC to differentiate between benign and
      malignant complex adnexal masses. RESULTS: Eighty-five patients were
      premenopausal, and 106 were postmenopausal. Seventy-four of the 202 ovarian
      masses were benign and 128 were malignant. There was a significant difference
      between the mean ADC values of benign and malignant ovarian masses (p < 0.05).
      However, there were no significant differences in ADC values between
      fibrothecomas, Brenner tumors and malignant ovarian masses. The ROC analysis
      indicated that a cutoff ADC value of 1.20 x10-3 mm2/s may be the optimal one for
      differentiating between benign and malignant tumors. CONCLUSIONS: A high signal
      intensity within the solid component on T2WI was less frequently in benign than
      in malignant adnexal masses. The combination of DW imaging with ADC value
      measurements and T2-weighted signal characteristics of solid components is useful
      for differentiating between benign and malignant ovarian masses.

PMID- 23137334
TI  - Positron emission tomography imaging of vascular endothelial growth factor
      receptor expression with (61)Cu-labeled lysine-tagged VEGF121.
AB  - Overexpression of vascular endothelial growth factor (VEGF) and VEGF receptors
      (VEGFRs) indicates poor prognosis for cancer patients in a variety of clinical
      studies. Our goal is to develop a tracer for positron emission tomography (PET)
      imaging of VEGFR expression using recombinant human VEGF121 with three lysine
      residues fused to the N-terminus (denoted as K3-VEGF121), which can facilitate
      radiolabeling without affecting its VEGFR binding affinity. K3-VEGF121 was
      conjugated with 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) and labeled
      with (61)Cu (t1/2: 3.3 h; 62% beta(+)). The IC50 value of NOTA-K3-VEGF121 for
      VEGFR-2 was comparable to that of K3-VEGF121 (1.50 and 0.65 nM, respectively)
      based on a cell binding assay. (61)Cu labeling was achieved with good yield (55
      +/- 10%) and specific activity (4.2 GBq/mg). Serial PET imaging showed that the
      4T1 tumor uptake of (61)Cu-NOTA-K3-VEGF121 was 3.4 +/- 0.5, 4.9 +/- 1.0, 5.2 +/-
      1.0, and 4.8 +/- 0.8%ID/g (n = 4) at 0.5, 2, 4, and 8 h postinjection,
      respectively, which was consistent with biodistribution data measured by gamma
      counting. Blocking experiments and ex vivo histology confirmed the VEGFR
      specificity of (61)Cu-NOTA-K3-VEGF121. Extrapolated human dosimetry calculation
      showed that liver was the organ with the highest radiation dose. The use of
      (61)Cu as the radiolabel is desirable for small proteins such as K3-VEGF121,
      which has a much higher beta(+) branching ratio than the commonly used (64)Cu
      (62% vs 17%), thereby offering stronger signal intensity and lower tracer dose
      for PET imaging. 

PMID- 23137335
TI  - Cultivating common ground: interdisciplinary approaches to biological research.

PMID- 23137336
TI  - Rational design, synthesis, evaluation and enzyme-substrate structures of
      improved fluorogenic substrates for family 6 glycoside hydrolases.
AB  - Methylumbelliferyl-beta-cellobioside (MUF-G2) is a convenient fluorogenic
      substrate for certain beta-glycoside hydrolases (GH). However, hydrolysis of the
      aglycone is poor with GH family 6 enzymes (GH6), despite strong binding.
      Prediction of the orientation of the aglycone of MUF-G2 in the +1 subsite of
      Hypocrea jecorina Cel6A by automated docking suggested umbelliferyl modifications
      at C4 and C6 for improved recognition. Four modified umbelliferyl-beta
      cellobiosides [6-chloro-4-methyl- (ClMUF); 6-chloro-4-trifluoromethyl- (ClF3MUF);
      4-phenyl- (PhUF); 6-chloro-4-phenyl- (ClPhUF)] were synthesized and tested with
      GH6, GH7, GH9, GH5 and GH45 cellulases. Indeed the rate of aglycone release by H.
      jecorina Cel6A was 10-150 times higher than with MUF-G2, although it was still
      three orders of magnitude lower than with H. jecorina Cel7B. The 4-phenyl
      substitution drastically reduced the fluorescence intensity of the free aglycone,
      while ClMUF-G2 could be used for determination of k(cat) and K(M) for H. jecorina
      Cel6A and Thermobifida fusca Cel6A. Crystal structures of H. jecorina Cel6A D221A
      mutant soaked with the MUF-, ClMUF- and ClPhUF-beta-cellobioside substrates show
      that the modifications turned the umbelliferyl group 'upside down', with the
      glycosidic bond better positioned for protonation than with MUF-G2.

PMID- 23137337
TI  - Chain-growth polymerization of 2-chlorothiophenes promoted by Lewis acids.
AB  - Lewis acids promote the polymerization of several 2
      chloroalkylenedioxythiophenes, providing high-molecular-weight conjugated
      polymers. The proposed mechanism is a cationic chain-growth polymerization, as
      confirmed by end-capping reactions and a linear correlation of molecular weight
      with percent conversion. The "living" character of this process was used to
      prepare new block copolymers.

PMID- 23137338
TI  - Postpartum mothers' napping and improved cognitive growth fostering of infants:
      results from a pilot study.
AB  - Little is known about how maternal sleep disturbances in the postpartum period
      affect mother-infant interaction. The study was designed to assess if less
      maternal sleep disturbance and less fatigue were associated with more positive
      mother-child interaction, independent of maternal depression symptoms. Twenty
      three mothers completed 1 week of actigraphy and self-report measures of fatigue
      and depression symptoms. To determine the quality of mother-infant interaction,
      mothers and infants were then observed in a structured, video-recorded teaching
      episode. Greater maternal napping frequency was associated with better cognitive
      growth fostering of the infant (r s = .44, p < .05), a subscale of the
      interaction assessment. Maternal napping, not the quality or quantity of
      nocturnal sleep, appears to be associated with improvements in mother-infant
      interactions.

PMID- 23137339
TI  - Immunosuppressive properties of a series of novel inhibitors of the
      monocarboxylate transporter MCT-1.
AB  - We have recently described the immunosuppressive properties of AR-C117977 and AR
      C122982, representatives of a group of compounds identified as inhibitors of
      lactate transporters (monocarboxylate transporters; MCTs). These compounds
      demonstrate the potential therapeutic usefulness of inhibiting MCT-1, but their
      physical and metabolic properties made them unsuitable for further development.
      We have therefore tried to find analogues with similar immunosuppressive efficacy
      and a more suitable profile for oral administration. Five analogues of AR-C117977
      were synthesised and screened for binding to the transporter, for inhibition of
      proliferation of both human and rat lymphocytes, for in vivo activity in a model
      of graft-versus-host (GvH) response in the rat, and in high- and low-responder
      cardiac transplant models in the rat. There was a good correlation between levels
      of binding of the five analogues to MCT and their inhibition of lymphocyte
      proliferation in human and rat cells. Furthermore, activity in both the GvH
      response and the cardiac transplant models correlated well with the determined
      concentrations of test compound in plasma. These findings on new analogues of MCT
      1 inhibitors have taken us further towards defining the pharmacokinetic
      properties that may help to identify future drug candidates among inhibitors of
      MCT-1.

PMID- 23137340
TI  - Rational design of potent non-nucleoside inhibitors of HIV-1 reverse
      transcriptase.
AB  - A new series of non-nucleoside reverse transcriptase inhibitors based on an
      imidazole-amide biarylether scaffold has been identified and shown to possess
      potent antiviral activity against HIV-1, including the NNRTI-resistant Y188L
      mutated virus. X-ray crystallography of inhibitors bound to reverse
      transcriptase, including a structure of the Y188L RT protein, was used
      extensively to help identify and optimize the key hydrogen-bonding motif. This
      led directly to the design of compound 43 that exhibits remarkable antiviral
      activity (EC50<1 nM) against a wide range of NNRTI-resistant viruses and a
      favorable pharmacokinetic profile across multiple species.

PMID- 23137341
TI  - Buckyplates and buckybowls: examining the effects of curvature on pi-pi
      interactions.
AB  - pi-pi interactions are integral to many areas of chemistry, biochemistry, and
      materials science. Here we use electronic structure theory to analyze how pi-pi
      interactions change as the pi-systems are curved in model complexes based on
      coronene and corannulene dimers. Curvature redistributes electronic charge in the
      pi-cloud and creates a dipole moment in these systems, leading to enhanced
      intermolecular electrostatic interactions in the concave-convex (nested)
      geometries that are the focus of this work. Curvature of both monomers also has a
      geometric effect on the interaction by decreasing the average C-C distance
      between monomers and by increasing the magnitude of both favorable London
      dispersion interactions and unfavorable exchange-repulsion interactions. Overall,
      increasing curvature in nested pi-pi interactions leads to more favorable
      interaction energies regardless of the native state of the monomers, except at
      short distances where the most highly curved systems are less favorable as
      exchange repulsion terms begin to dominate the interaction.

PMID- 23137342
TI  - A technique for placement of apical MTA plugs using modified Thermafil carriers
      for the filling of canals with wide apices.
AB  - AIM: To describe a technique for the placement of apical Mineral trioxide
      aggregate (MTA) plugs in canals with wide apices. SUMMARY: A novel technique to
      fill root canals with an apical diameter larger than 0.4 mm is presented. The
      technique includes three main stages; three Thermafil carriers of increasing
      size, previously de-sheathed by removing the Gutta-percha coating, are selected
      to engage 1, 2 and 3 mm short of the apex. Their use allows the negotiation of
      acute curvatures and ledged canals. Subsequently, an MTA plug matching the apical
      gauge is pre-formed with a pellet block, placed and condensed using the modified
      carriers in sequence. The presented protocol for the management of teeth with
      apices of a diameter greater than 0.4 mm allows a favourable apical control of
      the MTA. Clinical cases completed using this methodology are presented. KEY
      LEARNING POINTS: MTA placement in teeth with wide apices was facilitated by using
      de-sheathed Thermafil carriers, to create an appropriate seal and stable platform
      for Gutta-percha backfilling or subsequent fibre post placement. The use of de
      sheathed Thermafil carriers of different sizes allows predictable placement of
      pre-formed MTA plugs. Gauging of Thermafil carriers enhances control of the
      condensation phase to limit the extrusion of MTA.

PMID- 23137343
TI  - Dieulafoy's disease of the bronchus: a possible mistake.
AB  - We present a case of a 57 year old woman who suffered from massive hemoptysis;
      she was sent to our Department for a suspect neoformant lesion. We assumed it
      might be a Dielafoy's disease and proceeded with an imaging study that confirmed
      the diagnosis. After embolization the patient no longer showed signs of bleeding.
      In brief, we concluded that whenever there is a suspect of Dielafoy's disease,
      the biopsy has to be avoided.

PMID- 23137344
TI  - Antidiabetic components of Cassia alata leaves: identification through alpha
      glucosidase inhibition studies.
AB  - CONTEXT: Cassia alata Linn. [syn. Senna alata (L.) Roxb.] (Caesalpiniaceae) is
      used for treating various disease conditions including diabetes but its
      mechanism(s) of action and active principles remain to be elucidated. OBJECTIVE:
      The antidiabetic principles were identified using an in vitro alpha-glucosidase
      inhibition study. MATERIALS AND METHODS: The methanol extract of leaves of C.
      alata, which showed potent alpha-glucosidase inhibitory activity (IC50, 63.75 +/-
      12.81 ug/ml), was fractionated. Active fractions were taken for further analysis
      by a variety of techniques including HPLC and Combiflash chromatography. The
      identity of the isolated compounds was established by spectroscopic analysis
      while their potential antidiabetic activity was assessed by in vitro enzyme
      inhibition studies. RESULTS: The alpha-glucosidase inhibitory effect of the crude
      extract was far better than the standard clinically used drug, acarbose (IC50,
      107.31 +/- 12.31 ug/ml). A subsequent fractionation of the crude extract was made
      using solvents of ascending polarity (petroleum ether, chloroform, ethyl acetate,
      n-butanol and water). The ethyl acetate (IC50, 2.95 +/- 0.47 ug/ml) and n-butanol
      (IC50, 25.80 +/- 2.01 ug/ml) fractions which contained predominantly kaempferol
      (56.7 +/- 7.7 uM) and kaempferol 3-O-gentiobioside (50.0 +/- 8.5 uM),
      respectively, displayed the highest carbohydrate enzyme inhibitory effect.
      DISCUSSION: One of the possible antidiabetic mechanisms of action of C. alata is
      by inhibiting carbohydrate digestion. This is the first report on alpha
      glucosidase activity of kaempferol 3-O-gentiobioside. CONCLUSION: Considering the
      activity profile of the crude extract and isolated bioactive compounds, further
      in vivo and clinical studies on C. alata extracts and compounds are well merited.

PMID- 23137345
TI  - Lower incidence of recorded cardiovascular outcomes in patients with type 2
      diabetes using insulin aspart vs. those on human regular insulin: observational
      evidence from general practices.
AB  - AIMS: Insulin aspart has a higher ability to treat postprandial glucose than
      regular human insulin, which may have favourable cardiovascular effects. The aim
      was to collect and compare the incidence of recorded macro- and microvascular
      events in patients with type 2 diabetes with insulin aspart or regular human
      insulin in general practices. METHODS: Computerized data from 3154 aspart and
      3154 regular insulin users throughout Germany (Disease Analyzer, January 2000 to
      July 2011) were analysed after matching for age (60 +/- 10 years), sex (men:
      57%), health insurance (private: 5.8%) and diabetes treatment period in practice
      (2.2 +/- 2.5 years). Hazard ratios (HR; Cox regression) for macro- or
      microvascular outcomes (follow-up: 3.5 years) were further adjusted for
      diabetologist care, practice region, hypertension, hyperlipidaemia, co-medication
      (basal insulin, oral antidiabetics, antihypertensives, lipid-lowering agents and
      antithrombotic drugs), previous treatment with rapid-acting insulins,
      hypoglycaemia and the Charlson co-morbidity score. Furthermore, adjustment was
      carried out for baseline microvascular complications when analysing macrovascular
      outcomes and vice versa. RESULTS: Overall, the risk of combined macrovascular
      outcomes was 15% lower for insulin aspart users (p = 0.01). For insulin aspart
      there was also a decreased risk incident stroke [HR: 0.58; 95% confidence
      interval (CI): 0.45-0.74], myocardial infarction (HR: 0.69; 95% CI: 0.54-0.88)
      and peripheral vascular disease (HR: 0.80; 95% CI: 0.69-0.93). For microvascular
      complications (retinopathy, neuropathy and nephropathy), no significant
      differences were observed (HR: 0.96; 95% CI: 0.87-1.06). CONCLUSION: Use of the
      rapid-acting insulin analogue aspart was associated with a reduced incidence of
      macrovascular outcomes in type 2 diabetes in general practices. It is important
      to confirm this finding in a randomized controlled trial.

PMID- 23137346
TI  - Introduction of a hydrogen bond between phylloquinone PhQ(A) and a threonine side
      chain OH group in photosystem I.
AB  - The phylloquinone acceptor PhQ(A) in photosystem I binds to the protein through a
      single H-bond to the backbone nitrogen of PsaA-L722. Here, we investigate the
      effect of this H-bond on the electron transfer (ET) kinetics by substituting
      threonine for PsaA-L722. Room temperature spin-polarized transient EPR
      measurements show that in the PsaA-L722T mutant, the rate of PhQ(A)(-) to F(X) ET
      increases and the hyperfine coupling to the 2-methyl group of PhQ(A) is much
      larger than in the wild type. Molecular dynamics simulations and ONIOM type
      electronic structure calculations indicate that it is possible for the OH group
      of the Thr side chain to form an H-bond to the carbonyl oxygen atom, O(4) of the
      phylloquinone, and that this results in an increase in the 2-methyl hyperfine
      couplings as observed in the transient EPR data. The Arrhenius plot of the
      PhQ(A)(-) to F(X) ET in the PsaA-L722T mutant suggests that the increased rate is
      probably the result of a slight change in the electronic coupling between PhQ(A)(
      ) and F(X). The strong deviation from Arrhenius behavior observed at ~200 K can
      be reproduced using a semiclassical model, which takes the zero-point energy of
      the mode coupled to the ET into account. However, since the change in slope of
      the Arrhenius plot occurs at the protein glass transition temperature, it is
      argued that it could be the result of a change in the protein relaxation dynamics
      at this temperature rather than quantum mechanical effects.

PMID- 23137347
TI  - Relationship of fasting total homocysteine, high sensitivity C-reactive protein
      and features of the metabolic syndrome in Trinidadian subjects.
AB  - OBJECTIVES: To assess the relationship of homocysteine, hs-CRP, with known
      cardiovascular risk factors of the metabolic syndrome. METHOD: Cross sectional
      study comprised 182 diabetic outpatients (70 males and 112 females), attending
      endocrinology clinics in Trinidad. RESULTS: Both male and females showed
      significant linear relationships between high sensitive C-reactive protein (hs
      CRP), blood pressure and diabetes (r = -0.2 < R or R > 0.2). In females hs-CRP
      showed significant linear relationship with HDL, triglyceride, blood pressure and
      diabetes mellitus (p < 0.0001). The inverse relationship of hs-CRP with HDL
      implies the strong association of hs-CRP with metabolic syndrome. The
      multivariate logistic regression analysis showed significant relation of hs-CRP,
      metabolic syndrome and diabetes mellitus. There was no significant relationship
      of tHCY to any of the features studied. CONCLUSION: Serum C-reactive protein is
      significantly related to features of the metabolic syndrome. Total plasma
      homocysteine, appears to be independent of both hs-CRP and features of the
      metabolic syndrome.

PMID- 23137348
TI  - Relationship between prehypertension and chronic kidney disease in middle-aged
      people in Korea: the Korean genome and epidemiology study.
AB  - BACKGROUND: Elevated blood pressure (BP) is a major risk factor for the
      progression of chronic kidney disease (CKD). However, little is known about the
      influence of prehypertension on CKD. In this study, we investigated the
      relationship between prehypertension and CKD in a middle-aged Korean population.
      Furthermore, we prospectively evaluated the effect of active BP control on
      deterioration of kidney function during the two-year follow-up. METHODS: The
      Korean Genome and Epidemiology Study is a community-based prospective cohort
      study started in 2001, with a follow-up survey conducted every two years. A total
      of 9509 participants aged 40-69 years were included in a baseline study. BP was
      classified according to the Seventh Report of the Joint National Committee on
      High BP (JNC-7) categories and CKD was defined as the presence of proteinuria or
      eGFR< 60mL/min/1.73m(2). A multivariable logistic regression model was used to
      identify associations between BP and CKD. RESULTS: The overall prevalence of CKD
      was 13.2%, and significantly increased with BP level. The multivariable-adjusted
      odds ratio of CKD was 1.59 for prehypertension and 2.27 for hypertension,
      compared with a normal BP. At the two-year follow-up, among the participants with
      prehypertension, subjects whose BP was poorly controlled had a significantly
      higher risk of eGFR drop (OR, 1.37; 95% CI, 1.13-1.67), as compared to controls.
      The prevalence of eGFR drop was 57.8% in the controlled BP group and 66.0% in the
      poorly-controlled BP group. CONCLUSIONS: Prehypertension, as well as
      hypertension, is significantly associated with CKD among middle-aged Koreans. Our
      results indicate that active control of the blood-pressure of prehypertensive
      individuals is needed to prevent deterioration of kidney function.

PMID- 23137349
TI  - Aptamer modified organic-inorganic hybrid silica monolithic capillary columns for
      highly selective recognition of thrombin.
AB  - A novel kind of aptamer modified organic-inorganic hybrid silica monolithic
      capillary column has been developed, via the covalent bonding of 5'-NH(2)
      modified aptamer for human alpha-thrombin on hybrid silica monolith, prepared by
      sol-gel method, with tetraethoxysilane and 3-aminopropyltriethoxysilane as
      precursors. Due to the large specific surface area of the hybrid matrix, the
      average coverage density of aptamer reached 568 pmol/MUL, and the thrombin
      binding capacity was 1.15 MUg/MUL, 14 times higher than that of aptamer modified
      open tubular capillaries. By such an affinity capillary column, the limit of
      detection of thrombin was decreased to 3.4 nM with a UV detector. Furthermore,
      even when thrombin was mixed with 1000 times more concentrated human serum, it
      could be selectively enriched and detected with the signal-to-noise ratio as
      ca.10. These results indicate that the developed preparation strategy for aptamer
      based hybrid silica monolithic capillary column might provide an effective method
      to achieve highly selective recognition of trace targets.

PMID- 23137351
TI  - Structural annotation of human carbonic anhydrases.
AB  - Carbonic anhydrases (CAs, EC 4.2.1.1) are a family of metalloenzymes that
      catalyze the reversible interconversion of CO(2) and HCO(3)(-). Of the 15
      isoforms of human (h) alpha-CA, 12 are catalytic (hCAs I-IV, VA, VB, VI, VII, IX,
      XII-XIV). The remaining three acatalytic isoforms (hCAs VIII, X and XI) lack the
      active site Zn(2+) and are referred to as CA-related proteins (CA-RPs); however,
      their function remains elusive. Overall these isoforms are very similar to each
      other in structure but they differ in their expression and distribution. The
      favourable properties of hCA II such as fast kinetics, easy expression and
      purification, high solubility and intermediate heat resistance have made it an
      attractive candidate for numerous industrial applications. This review highlights
      the structural similarity and stability comparison among hCAs.

PMID- 23137350
TI  - Low-dose plasmid DNA treatment increases plasma vasopressin and regulates blood
      pressure in experimental endotoxemia.
AB  - BACKGROUND: Although plasmid DNA encoding an antigen from pathogens or tumor
      cells has been widely studied as vaccine, the use of plasmid vector (without
      insert) as therapeutic agent requires further investigation. RESULTS: Here, we
      showed that plasmid DNA (pcDNA3) at low doses inhibits the production of IL-6 and
      TNF-alpha by lipopolysaccharide (LPS)-stimulated macrophage cell line J774. These
      findings led us to evaluate whether plasmid DNA could act as an anti-inflammatory
      agent in a Wistar rat endotoxemia model. Rats injected simultaneously with 1.5
      mg/kg of LPS and 10 or 20 MUg of plasmid DNA had a remarkable attenuation of mean
      arterial blood pressure (MAP) drop at 2 hours after treatment when compared with
      rats injected with LPS only. The beneficial effect of the plasmid DNA on MAP was
      associated with decreased expression of IL-6 in liver and increased concentration
      of plasma vasopressin (AVP), a known vasoconstrictor that has been investigated
      in hemorrhagic shock management. No difference was observed in relation to nitric
      oxide (NO) production. CONCLUSION: Our results demonstrate for the first time
      that plasmid DNA vector at low doses presents anti-inflammatory property and
      constitutes a novel approach with therapeutic potential in inflammatory diseases.

PMID- 23137352
TI  - Platelet function normalization after a prasugrel loading-dose: time-dependent
      effect of platelet supplementation.
AB  - BACKGROUND: Hemostatic benefits of platelet transfusions in thienopyridine
      treated acute coronary syndrome (ACS) patients may be compromised by residual
      metabolite in circulation. OBJECTIVES: To estimate the earliest time after a
      prasugrel loading-dose when added platelets are no longer inhibited by
      prasugrel's active metabolite. METHODS: Baseline platelet reactivity of healthy
      subjects (n=25, 30 +/- 5 years, 68% male) on ASA 325 mg was tested using maximum
      platelet aggregation (MPA, ADP 20 MUm) and VerifyNow((r)) P2Y12 and was followed
      by a 60 mg prasugrel loading-dose. At 2, 6, 12 and 24 h post-dose, fresh
      concentrated platelets from untreated donors were added ex-vivo to subjects'
      blood, raising platelet counts by 0% (control), 40%, 60% and 80%. To estimate the
      earliest time when prasugrel's active metabolite's inhibitory effect on the added
      platelets ceases, platelet function in supplemented samples was compared across
      time-points to identify the time when effect of supplementation on platelet
      function stabilized (i.e. the increase in platelet reactivity was statistically
      similar to that at the next time-point). RESULTS: Supplemented samples showed
      concentration-dependent increases in platelet reactivity vs. respective controls
      by both MPA and VerifyNow((r)) at all assessment time-points. For each
      supplementation level, platelet reactivity showed a sharp increase from 2 to 6 h
      but was stable (P=NS) between 6 and 12 h. CONCLUSIONS: The earliest measured time
      when supplemented platelets were not inhibited by circulating active metabolite
      of prasugrel was 6 h after a prasugrel loading-dose. These findings may have
      important implications for prasugrel-treated ACS patients requiring platelet
      transfusions during surgery.

PMID- 23137353
TI  - Daytime course of sleepiness in de novo Parkinson's disease patients.
AB  - Normal subjects show an increase of sleepiness in the morning, early afternoon
      and before sleep. In the advanced stages of Parkinson's disease (PD) the mean
      level of sleepiness is quite high, while with respect to healthy subjects it
      seems to be unchanged in the early stages. The aim of this study was to evaluate
      the time-course of the sleepiness level during the wakefulness period in
      untreated patients with early-stage Parkinson's disease. Eighteen Parkinson's
      disease patients who had never been treated before with dopaminergic drugs (male
      = 9, female = 9, age: 68.39 +/- 1.89, mean +/- standard error) and 18 healthy
      subjects (male = 9, female = 9, age: 67.22 +/- 1.98) were recruited for this
      study. All subjects underwent continuous actigraphic recording for three
      consecutive days, during which they also completed the Karolinska Sleepiness
      Scale (KSS) once an hour throughout wakefulness. Our results showed a higher
      level of sleepiness in the patients than the controls in the hours following
      awakening and in the early afternoon, specifically at 08:00 and 14:00 hours
      (08:00 hours, PD patients, KSS: 3 +/- 0.3 versus healthy subjects, KSS: 2 +/-
      0.2, P < 0.05; 14:00 hours, PD patients, KSS: 4.4 +/- 0.5 versus healthy
      subjects, KSS: 3 +/- 0.3, P < 0.05). We suggest that some daytime hours are
      sensitive windows showing the first increase of sleepiness which will spread
      later to the whole daytime.

PMID- 23137354
TI  - Morphological characteristics of the vallate papillae of the one-humped camel
      (Camelus dromedarius).
AB  - In this study, the morphology of the vallate papillae of camel was investigated
      using gross, light and scanning electron microscopy as well as
      immunohistochemistry. Vallate papillae were arranged along an identical line on
      each side of the lingual torus and revealed remarkable individual differences.
      However, each papilla - round or flat, small or large, single or paired - was
      surrounded by a prominent groove and an annular pad. Based on our findings,
      postnatal development and formation of new papillae occur in camel.
      Microscopically, taste buds were constantly observed along the medial wall
      epithelium, and in the papillary wall epithelium on both sides of the secondary
      groove apparently separating the vallate papillae. In addition, an aggregation of
      taste buds was occasionally observed at the bottom of the lateral wall
      epithelium. Using SEM, we observed several pits and microplicae on the surface of
      papillae as well as distinct taste pores on the peripheral parts of the dorsal
      surface. We demonstrated immunoreactivity of alpha-gustducin only in mature taste
      buds. We conclude that the morphological features and microstructure of vallate
      papillae are a characteristic feature in camel compared to other ruminants. These
      features might have evolved to assist the camel in the manipulation and tasting
      of thin organic stiff plants that grow in its environment and therefore might
      have related to the feeding habits of the animal.

PMID- 23137356
TI  - Lead level in seminal plasma may affect semen quality for men without
      occupational exposure to lead.
AB  - BACKGROUND: Infertility affects approximately 10-15% of reproductive-age couples.
      Poor semen quality contributes to about 25% of infertile cases. Resulting from
      the direct effect on testicular function or hormonal alterations, heavy metals
      exposure has been related to impaired semen quality. The objective of this study
      was to assess the level of lead in the seminal plasma in men without occupational
      exposure to lead, and to determine the relationship between semen quality and
      lead concentration in the semen. METHODS: This is a prospective and nonrandomized
      clinical study conducted in University infertility clinic and academic research
      laboratory. Three hundred and forty-one male partners of infertile couples
      undergoing infertility evaluation and management were recruited to the study.
      Semen samples collected for the analyses of semen quality were also used for the
      measurement of lead concentrations. Semen samples were evaluated according to the
      WHO standards. RESULTS: All subjects were married and from infertile couples
      without occupational exposure to lead. There is a significant inverse correlation
      between the lead concentration in seminal plasma and sperm count. A higher semen
      lead concentration was correlated with lower sperm count, but not with semen
      volume, sperm motility or sperm morphology as assessed by simple linear
      regression. CONCLUSIONS: We found that semen lead concentration was significantly
      higher among the patients with lower sperm count. To our knowledge, this is the
      first study to demonstrate that a high level of lead accumulation in semen may
      reduce the sperm count contributing to infertility of men without occupational
      exposure to lead.

PMID- 23137358
TI  - Leading through Change.

PMID- 23137357
TI  - GsmR, a response regulator with an HD-related output domain in Xanthomonas
      campestris, is positively controlled by Clp and is involved in the expression of
      genes responsible for flagellum synthesis.
AB  - In prokaryotes, two-component signal transduction systems, consisting of a
      histidine kinase and a response regulator, play a critical role in regulating a
      range of cellular functions. A recent study suggests that XCC3315, a response
      regulator with a CheY-like receiver domain attached to an uncharacterized HD
      related output domain (HDOD domain), plays a role in the general stress response
      of the Gram-negative bacterium Xanthomonas campestris pv. campestris (Xcc), the
      causal agent of black rot in cruciferous plants. Here, we demonstrated
      genetically that XCC3315, designated as gsmR (general stress and motility
      regulator), is involved in the expression of genes responsible for flagellum
      synthesis, including rpoN2, flhF, flhB, and fliC. Site-directed mutagenesis
      revealed that Glu9 and Arg100 in the receiver domain and Gly205, Asp263, His287,
      Trp298 and His311 in the HDOD are critical amino acids for GsmR function in cell
      motility regulation. The gsmR transcription initiation site was mapped. Promoter
      analysis and gel retardation assay revealed that the expression of gsmR is
      positively controlled by the global transcriptional regulator Clp in a direct
      manner, and is subject to catabolite repression. Our findings not only extend the
      previous work on Clp regulation to show that it influences the expression of gsmR
      in Xcc, but are also the first to characterize the expression of this response
      regulator gene in this phytopathogen. Furthermore, GsmR is the first HDOD
      containing protein of bacteria in which key amino acids have been experimentally
      identified and characterized.

PMID- 23137359
TI  - Political discussions in the exam room.

PMID- 23137360
TI  - Physician involvement with politics-obligation or avocation?

PMID- 23137361
TI  - New guidelines for cancer screening in older patients.

PMID- 23137362
TI  - Graduate medical education financing and the role of the volunteer educator.

PMID- 23137363
TI  - The American Medical Association Code of Medical Ethics' Opinion on Pay-for
      Performance Programs and Patients' Interests.

PMID- 23137364
TI  - The effects of congressional budget reconciliation on health care reform.

PMID- 23137365
TI  - The Physician Group Practice Demonstration-A Valuable Model for ACOs?

PMID- 23137366
TI  - Constitutional challenges to the patient protection and affordable care act-a
      snapshot.

PMID- 23137367
TI  - Maine's Medical Liability Demonstration Project-Linking Practice Guidelines to
      Liability Protection.

PMID- 23137368
TI  - Aligning values with value.

PMID- 23137369
TI  - American medical association policy-the individual mandate and individual
      responsibility.

PMID- 23137370
TI  - Health reform and the future of medical practice.

PMID- 23137371
TI  - How medicare and hospitals have shaped american health care.

PMID- 23137372
TI  - Inside the Senate-A Physician Congressional Fellow's Experience with Health Care
      Reform.

PMID- 23137373
TI  - The affordable care act-a new way forward.

PMID- 23137374
TI  - ObamaCare-The Way of the Dodo.

PMID- 23137375
TI  - About the contributors.

PMID- 23137376
TI  - Multidrug resistance reversal and apoptosis induction in human colon cancer cells
      by some flavonoids present in citrus plants.
AB  - Multidrug resistance (MDR) of cancer cells constitutes one of the main reasons
      for chemotherapy failure. The search for nontoxic modulators that reduce MDR is a
      task of great importance. An ability to enhance apoptosis of resistant cells
      would also be beneficial. In the present study, the MDR reversal and apoptosis
      inducing potency of three flavonoids produced by Citrus plants, namely,
      naringenin (1a), aromadendrin (2), and tangeretin (3), and the methylated
      naringenin derivatives (1b, 1c), have been studied in sensitive (LoVo) and
      multidrug-resistant (LoVo/Dx) human colon adenocarcinoma cells. Cytotoxicity of
      methoxylated flavonoids was higher as compared to hydroxylated analogues. Only 3
      turned out to inhibit P-glycoprotein, as demonstrated by a rhodamine 123
      accumulation assay. It also increased doxorubicin accumulation in LoVo/Dx cells
      and enabled doxorubicin to enter cellular nuclei. In addition, 3 was found to be
      an effective MDR modulator in resistant cells by sensitizing them to doxorubicin.
      Tangeretin-induced caspase-3 activation and elevated surface phosphatidylserine
      exposure demonstrated its apoptosis-inducing activity in LoVo/Dx cells, while the
      other flavonoids evaluated were not active. Additionally, 3 was more toxic to
      resistant rather than to sensitive cancer cells. Its apoptosis-inducing activity
      was also higher in LoVo/Dx than in LoVo cells. It was concluded that the activity
      of 3 against multidrug-resistant cancer cells may be enhanced by its apoptosis
      inducing activity. 

PMID- 23137377
TI  - Quantitative targeted absolute proteomic analysis of transporters, receptors and
      junction proteins for validation of human cerebral microvascular endothelial cell
      line hCMEC/D3 as a human blood-brain barrier model.
AB  - Human cerebral microvascular endothelial cell line hCMEC/D3 is an established
      model of the human blood-brain barrier (BBB). The purpose of the present study
      was to determine, by means of quantitative targeted absolute proteomics, the
      protein expression levels in hCMEC/D3 cells of multiple transporters, receptors
      and junction proteins for comparison with our previously reported findings in
      isolated human brain microvessels. Among 91 target molecules, 12 transporters, 2
      receptors, 1 junction protein and 1 membrane marker were present at quantifiable
      levels in plasma membrane fraction of hCMEC/D3 cells. ABCA2, MDR1, MRP4, BCRP,
      GLUT1, 4F2hc, MCT1, ENT1, transferrin and insulin receptors and claudin-5 were
      detected in both hCMEC/D3 cells and human brain microvessels. After normalization
      based on Na(+)/K(+) ATPase expression, the differences in protein expression
      levels between hCMEC/D3 cells and human brain microvessels were within 4-fold for
      these proteins, with the exceptions of ENT1, transferrin receptor and claudin-5.
      ABCA8, LAT1, LRP1 and gamma-GTP were below the limit of quantification in the
      cells, but were found in human brain microvessels. ABCA3, ABCA6, MRP1 and ATA1
      were found only in hCMEC/D3 cells. Furthermore, compared with human umbilical
      vein endothelial cells (HUVECs) as reference nonbrain endothelial cells, MDR1 was
      found only in hCMEC/D3 cells, and GLUT1 expression was 15-fold higher in hCMEC/D3
      cells than in HUVECs. In conclusion, this is the first study to examine the
      suitability and limitations of the hCMEC/D3 cell line as a BBB functional model
      in terms of quantitative expression levels of transporters, receptors and tight
      junction proteins.

PMID- 23137378
TI  - Initial metformin or sulphonylurea exposure and cancer occurrence among patients
      with type 2 diabetes mellitus.
AB  - AIM: This was a retrospective cohort study of type 2 diabetes patients, to
      evaluate the association between initial metformin or sulphonylurea treatment and
      cancer incidence. METHODS: Patients identified in the UK Clinical Practice
      Research Datalink (CPRD), previously General Practice Research Database, during
      1995-2008 who were initially stabilized on OHA monotherapy, including metformin,
      sulphonylurea, thiazolidinediones (TZDs) or meglitinides, were included in the
      cohort. New diagnoses of cancer, including malignant solid tumours and
      haematological malignancies, occurring during the follow-up were identified from
      the cohort. Age-standardized incidence rates were estimated and compared between
      metformin and sulphonylurea exposure groups. RESULTS: The age standardized
      incidences of cancer were 7.5 and 8.5 per 1000 person-years for the metformin and
      sulphonylurea exposure groups, respectively. After adjusting for potential
      confounders, the hazard ratios (HR) for malignant solid tumours and
      haematological malignancies were 1.06 (95% CI: 0.98, 1.15) and 0.98 (95% CI:
      0.67, 1.43) for sulphonylurea group as compared to the metformin group,
      respectively. For individual cancers, the HRs were 1.17 (95% CI: 0.95, 1.44),
      1.04 (95% CI: 0.83, 1.31) and 0.88 (95% CI: 0.71, 1.11) for colorectal cancer,
      breast cancer and prostate cancer, respectively. CONCLUSION: This study provides
      evidence that cancer incidence in the first few years after starting metformin or
      sulphonylurea therapy in type 2 diabetes patients is not much affected by choice
      of hypoglycaemic drug class.

PMID- 23137379
TI  - [Patient safety: Everyone is talking about it, progress is being made, but (too)
      slowly].

PMID- 23137380
TI  - [Patient safety and economy].

PMID- 23137381
TI  - [Patient deaths are not suited for monitoring quality and patient safety in
      hospitals].
AB  - Although some patient deaths in hospitals can be prevented if quality of care and
      patient safety are improved, it is not given that such deaths can be used to
      track improvements. Since preventable deaths only amount to about 5% of all
      deaths, a decline in that number will be a weak signal as far as mortality is
      concerned. The commonly used hospital standardised mortality ratio (HSMR) has a
      low signal-to-noise ratio and is therefore not suitable for monitoring. The same
      goes for structured reviews of health-care records of deceased patients.
      Consequently, a need to develop alternatives exists.

PMID- 23137382
TI  - [Relations between health information systems and patient safety].
AB  - Health information systems have the potential to reduce medical errors, and
      indeed many studies have shown a significant reduction. However, if the systems
      are not designed and implemented properly, there is evidence that suggest that
      new types of errors will arise--i.e., technology-induced errors. Health
      information systems will need to undergo a more rigorous evaluation. Usability
      evaluation and simulation test with humans in the loop can help to detect and
      prevent technology-induced errors before they are deployed in real health-care
      settings.

PMID- 23137383
TI  - [Safe medication by means of cross-sectoral medication reconciliation].
AB  - Lack of medication reconciliation (MR) during transition in care is a major
      source to preventable, adverse drug events (PADE). At admission it is crucial
      that a thorough medication history is obtained in order to prevent discrepancies
      in the medication list. Still, discrepancies occur and one third of them have the
      potential to harm the patient. Systematic MR has proved to prevent PADE. The
      process of implementing MR is complex. Preliminary results from The Danish Safer
      Hospital Programme show, that comprehensive intervention is the key to success.
      Further research into interventions and implementation of MR in a clinical
      setting is needed.

PMID- 23137384
TI  - [Patient safety can be ensured in clinical microsystems].
AB  - Patients, health-care professionals and the public expect safe health care. The
      system, however, is not safe and patients are being harmed. Workplace and
      organizational conditions and human factors contribute to these harms and a
      system approach is needed to avoid them. In clinical microsystems (CMS), the
      frontline units of health care, staff and patients can make care safer by
      learning about their system, its processes, members and purposes. Approaches from
      patient safety should be integrated in the daily work of every member of the CMS
      to reduce risk, implement safe practices and learn from errors. We summarize
      methods for use in CMS and offer ideas for fostering a proactive culture of
      patient safety.

PMID- 23137385
TI  - [Patient safety in a new perspective].
AB  - Effective health care depends on the safe and efficient functioning of a tightly
      coupled multitude of systems, functions, and specialised services. Both theory
      and practice have demonstrated how safety management that follows events becomes
      reduced to uncoordinated and fragmentary fire-fighting. This reactive safety
      management is inadequate. Safety management should be based on an understanding
      of why everyday performance as a rule goes well rather than on why it
      occasionally fails, and actively use this to improve the former (safety-II)
      rather than simply preventing the latter (safety-I).

PMID- 23137386
TI  - [Patient involvement in patient safety is necessary, but the effect is
      undocumented].
AB  - Patient involvement has been on the patient safety agenda for years. Several
      initiatives have been launched, but in spite of support from health-care
      professionals, patients and administrators the concept is not yet integrated in
      every day clinical practice. The vision is to create partnerships for the purpose
      of preventing patients from harm due to their contact to health care. The
      literature offers good ideas but is also characterized by lack of methodological
      rigor. A change of values and habits, a supportive infrastructure and further
      research is needed to reach the goal.

PMID- 23137387
TI  - [Patient-centered care in Danish hospitals will heighten the quality].
AB  - Patient-centered care is a multidimensional quality goal, which aims at
      establishing a partnership between doctors and patients and to ensure that
      clinical practices are based on the individual patient's needs and preferences.
      In this article the concept of patient-centered care and how to apply this in a
      hospital setting is sought clarified. The principles of patient-centered care and
      the organizational preconditions needed for the implementation of this are
      described based on the literature, followed by a discussion of the status and
      challenges in Danish health care. We conclude that a stronger focus on patient
      centered care is needed.

PMID- 23137388
TI  - Gas-phase energetics of thorium fluorides and their ions.
AB  - Gas-phase thermochemistry for neutral ThF(n) and cations ThF(n)(+) (n = 1-4) is
      obtained from large-basis CCSD(T) calculations, with a small-core pseudopotential
      on thorium. Electronic partition functions are computed with the help of
      relativistic MRCI calculations. Geometries, vibrational spectra, electronic fine
      structure, and ion appearance energies are tabulated. These results support the
      experimental results by Lau, Brittain, and Hildenbrand for the neutral species,
      except for ThF. The ion thermochemistry is presented here for the first time.

PMID- 23137389
TI  - Comparison of different treatments for oestrous induction in seasonally
      anovulatory mares.
AB  - The aim of this study was to evaluate the effects of different treatments for
      induction and synchronization of oestrus and ovulation in seasonally anovulatory
      mares. Fifteen mares formed the control group (C), while 26 mares were randomly
      assigned to three treatment groups. Group T1 (n = 11) were treated with oral
      altrenogest (0.044 mg/kg; Regumate((r)) ) during 11 days. Group T2 (n = 7) was
      intravaginally treated with 1.38 g of progesterone (CIDR((r)) ) for 11 days. In
      group T3 (n = 8), mares were also treated with CIDR((r)) , but only for 8 days.
      All mares received PGF2alpha 1 day after finishing the treatment. Sonographic
      evaluation of follicles, pre-ovulatory follicle size and ovulation time was
      recorded. Progesterone and leptin levels were analysed. Results show that pre
      ovulatory follicles were developed after the treatment in 88.5% of mares.
      However, the pre-ovulatory follicle growth was dispersal, and sometimes it was
      detected when treatment was not finished. While in mares treated with
      intravaginal device, the follicle was soon detected (1.5 +/- 1.2 days and 2.3 +/-
      2.0 days in T2 and T3 groups, respectively), in T1 group, the pre-ovulatory
      follicle was detected slightly later (3.9 +/- 1.6 days). The interval from the
      end of treatment to ovulation did not show significant differences between groups
      (T1 = 13.1 +/- 2.5 days; T2 = 11.0 +/- 3.6 days; T3 = 13.8 +/- 4.3 days). The
      pregnancy rate was 47.4%, similar to the rate observed in group C (46.7%; p >
      0.05). Initial leptin concentrations were significantly higher in mares, which
      restart their ovarian activity after treatments, suggesting a role in the
      reproduction mechanisms in mares. It could be concluded that the used treatments
      may be effective for oestrous induction in mares during the late phase of the
      seasonally anovulatory period. Furthermore, they cannot synchronize oestrus, and
      then, it is necessary to know the reproductive status of mares when these
      treatments are used for oestrous synchronization.

PMID- 23137391
TI  - Evaluation of drug-induced tissue injury by measuring alanine aminotransferase
      (ALT) activity in silkworm hemolymph.
AB  - BACKGROUND: Our previous studies suggest silkworms can be used as model animals
      instead of mammals in pharmacologic studies to develop novel therapeutic
      medicines. We examined the usefulness of the silkworm larvae Bombyx mori as an
      animal model for evaluating tissue injury induced by various cytotoxic drugs.
      Drugs that induce hepatotoxic effects in mammals were injected into the silkworm
      hemocoel, and alanine aminotransferase (ALT) activity was measured in the
      hemolymph 1 day later. RESULTS: Injection of CCl4 into the hemocoel led to an
      increase in ALT activity. The increase in ALT activity was attenuated by
      pretreatment with N-acetyl-L-cysteine. Injection of benzoic acid derivatives,
      ferric sulfate, sodium valproate, tetracycline, amiodarone hydrochloride,
      methyldopa, ketoconazole, pemoline (Betanamin), N-nitroso-fenfluramine, and D
      galactosamine also increased ALT activity. CONCLUSIONS: These findings indicate
      that silkworms are useful for evaluating the effects of chemicals that induce
      tissue injury in mammals.

PMID- 23137392
TI  - Design and evaluation of a novel nanoparticulate-based formulation encapsulating
      a HIP complex of lysozyme.
AB  - Formulation development of protein therapeutics using polymeric nanoparticles has
      found very little success in recent years. Major formulation challenges include
      rapid denaturation, susceptibility to lose bioactivity in presence of organic
      solvents and poor encapsulation in polymeric matrix. In the present study, we
      have prepared hydrophobic ion pairing (HIP) complex of lysozyme, a model protein,
      using dextran sulfate (DS) as a complexing polymer. We have optimized the process
      of formation and dissociation of HIP complex between lysozyme and DS. The effect
      of HIP complexation on enzymatic activity of lysozyme was also studied.
      Nanoparticles were prepared and characterized using spontaneous emulsion solvent
      diffusion method. Furthermore, we have also investigated release of lysozyme from
      nanoparticles along with its enzymatic activity. Results of this study indicate
      that nanoparticles can sustain the release of lysozyme without compromising its
      enzymatic activity. HIP complexation using a polymer may also be employed to
      formulate sustained release dosage forms of other macromolecules with enhanced
      encapsulation efficiency.

PMID- 23137393
TI  - Skeletal myogenic differentiation of urine-derived stem cells and angiogenesis
      using microbeads loaded with growth factors.
AB  - To provide site-specific delivery and targeted release of growth factors to
      implanted urine-derived stem cells (USCs), we prepared microbeads of alginate
      containing growth factors. The growth factors included VEGF, IGF-1, FGF-1, PDGF,
      HGF and NGF. Radiolabeled growth factors were loaded separately and used to
      access the in vitro release from the microbeads with a gamma counter over 4
      weeks. In vitro endothelial differentiation of USCs by the released VEGF from the
      microbeads in a separate experiment confirmed that the released growth factors
      from the microbeads were bioactive. USCs and microbeads were mixed with the
      collagen gel type 1 (2 mg/ml) and used for in vivo studies through subcutaneous
      injection into nude mice. Four weeks after subcutaneous injection, we found that
      grafted cell survival was improved and more cells expressed myogenic and
      endothelial cell transcripts and markers compared to controls. More vessel
      formation and innervations were observed in USCs combined with six growth factors
      cocktail incorporated in microbeads compared to controls. In conclusion, a
      combination of growth factors released locally from the alginate microbeads
      induced USCs to differentiate into a myogenic lineage, enhanced revascularization
      and innervation, and stimulated resident cell growth in vivo. This approach could
      potentially be used for cell therapy in the treatment of stress urinary
      incontinence.

PMID- 23137394
TI  - Autoregulation of thromboinflammation on biomaterial surfaces by a multicomponent
      therapeutic coating.
AB  - Activation of the thrombotic and complement systems is the main recognition and
      effector mechanisms in the multiple adverse biological responses triggered when
      biomaterials or therapeutic cells come into blood contact. We have created a
      surface which is auto-protective to human innate immunity by combining three
      fundamentally different strategies, all developed by us previously, which have
      been shown to induce substantial, but incomplete hemocompatibility when used
      separately. In summary, we have conjugated a factor H-binding peptide; and an ADP
      degrading enzyme; using a PEG linker on both material and cellular surfaces. When
      exposed to human whole blood, factor H was specifically recruited to the modified
      surfaces and inhibited complement attack. In addition, activation of platelets
      and coagulation was efficiently attenuated, by degrading ADP. Thus, by inhibiting
      thromboinflammation using a multicomponent approach, we have created a hybrid
      surface with the potential to greatly reduce incompatibility reactions involving
      biomaterials and transplantation.

PMID- 23137395
TI  - Lipid modified triblock PAMAM-based nanocarriers for siRNA drug co-delivery.
AB  - RNA interference by small interfering RNA (siRNA) holds promise to attenuate
      production of specific target proteins but is challenging in practice owing to
      the barriers for its efficient intracellular delivery. We have synthesized a
      triblock co-polymeric system, poly(amidoamine) dendrimer (generation 4)
      poly(ethylene glycol)-1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (G(4)-D-PEG
      (2K)-DOPE). G(4)-PAMAM dendrimer was utilized as a cationic source for efficient
      siRNA condensation; DOPE provided optimum hydrophobicity and compatible cellular
      interaction for enhanced cell penetration; PEG rendered flexibility to the G(4)-D
      for easy accessibility of siRNA for condensation; PEG-DOPE system provided stable
      micellization in a mixed micellar system. G(4)-D-PEG-(2K)-DOPE was incorporated
      into the self-assembled PEG-(5K)-PE micelles at a 1:1 molar ratio. Our results
      demonstrate that the modified dendrimer, G(4)-D-PEG-(2K)-DOPE and the micellar
      nanocarrier form stable polyplexes with siRNA, shows excellent serum stability
      and a significantly higher cellular uptake of siRNA that results in target
      protein down-regulation when compared to the G(4)-PAMAM dendrimer. Moreover, the
      mixed micellar system showed efficient micellization and higher drug
      (doxorubicin) loading efficiency. The G(4)-D-PEG-(2K)-DOPE has the higher
      efficacy for siRNA delivery, whereas G(4)-D-PEG-(2K)-DOPE/PEG-(5K)-PE micelles
      appear to be a promising carrier for drug/siRNA co-delivery, especially useful
      for the treatment of multi-drug resistant cancers.

PMID- 23137396
TI  - Photothermal cancer therapy via femtosecond-laser-excited FePt nanoparticles.
AB  - FePt nanoparticles (NPs) have recently been revealed to be significant
      multifunctional materials for the applications of biomedical imaging, drug
      delivery and magnetic hyperthermia due to their novel magnetic properties. In
      this study, a newly discovered photothermal effect activated by the near infrared
      (NIR) femtosecond laser for FePt NPs was demonstrated. The threshold laser energy
      to destroy cancer cells was found to be comparable to that of gold nanorods (Au
      NRs) previously reported. Through the thermal lens technique, it was concluded
      that the temperature of the FePt NPs can be heated up to a couple of hundreds
      degree C in picoseconds under laser irradiation due to the excellent photothermal
      transduction efficiency of FePt NPs. This finding boosts FePt NPs versatility in
      multifunctional targeted cancer therapy.

PMID- 23137397
TI  - A versatile coiled-coil tethering system for the oriented display of ligands on
      nanocarriers for targeted gene delivery.
AB  - Surface modification of non-viral gene delivery nanocarriers may provide advanced
      features such as receptor targeting, endosomal escape and nuclear import. We here
      report the design of a versatile and tunable immobilization protocol to
      functionalize nanocarriers for improved transient gene expression. Our strategy
      is based on specific interactions occurring between a coil-tagged ligand and a
      complementary coil-functionalized nanocarrier. As a proof of concept, targeting
      of DNA/polyethylenimine polyplexes to the epidermal growth factor receptor of
      A431 cells was investigated. Coiled-coil-mediated oriented tethering of epidermal
      growth factor triggered a drastic increase of the internalization rate of the
      targeted polyplexes. To explore the tunability of our platform, surface density
      of targeting ligand was varied; our results indicated that the internalization
      rate varied with the ligand-to-polyplex ratio in a "switch mode" fashion. This
      work prefigures possible avenues for our coiled-coil platform in multiplex
      functionalization to address transient gene expression bottlenecks in recombinant
      protein production.

PMID- 23137390
TI  - Age of major depression onset, depressive symptoms, and risk for subsequent
      dementia: results of the German study on Ageing, Cognition, and Dementia in
      Primary Care Patients (AgeCoDe).
AB  - BACKGROUND: Whether late-onset depression is a risk factor for or a prodrome of
      dementia remains unclear. We investigated the impact of depressive symptoms and
      early- v. late-onset depression on subsequent dementia in a cohort of elderly
      general-practitioner patients (n = 2663, mean age = 81.2 years). METHOD: Risk for
      subsequent dementia was estimated over three follow-ups (each 18 months apart)
      depending on history of depression, particularly age of depression onset, and
      current depressive symptoms using proportional hazard models. We also examined
      the additive prediction of incident dementia by depression beyond cognitive
      impairment. RESULTS: An increase of dementia risk for higher age cut-offs of late
      onset depression was found. In analyses controlling for age, sex, education, and
      apolipoprotein E4 genotype, we found that very late-onset depression (aged >= 70
      years) and current depressive symptoms separately predicted all-cause dementia.
      Combined very late-onset depression with current depressive symptoms was
      specifically predictive for later Alzheimer's disease (AD; adjusted hazard ratio
      5.48, 95% confidence interval 2.41-12.46, p < 0.001). This association was still
      significant after controlling for cognitive measures, but further analyses
      suggested that it was mediated by subjective memory impairment with worries.
      CONCLUSIONS: Depression might be a prodrome of AD but not of dementia of other
      aetiology as very late-onset depression in combination with current depressive
      symptoms, possibly emerging as a consequence of subjectively perceived worrisome
      cognitive deterioration, was most predictive. As depression parameters and
      subjective memory impairment predicted AD independently of objective cognition,
      clinicians should take this into account.

PMID- 23137398
TI  - Emergencies in early pregnancy.
AB  - First-trimester vaginal bleeding and abdominal pain are common complaints in the
      emergency department. The differential diagnosis is broad, ranging from benign
      conditions to life-threatening complications. This is a difficult topic because
      it is charged not only with immediate emotional connotations but also with
      potential long-term effects on the patient's ability to become pregnant again.
      This article reviews the presentation, diagnosis, and management of implantation
      bleeding, subchorionic hemorrhage, spontaneous abortion, ectopic pregnancy,
      heterotopic pregnancy, anembryonic pregnancy, hyperemesis gravidarum, gestational
      trophoblastic disease, and round ligament syndrome.

PMID- 23137399
TI  - Ultrasound in pregnancy.
AB  - For the emergency physician tasked with evaluating the patient with an obstetric
      emergency, ultrasound can provide important and potentially life-saving
      information. Ultrasound of the pregnant patient is unique in that two possible
      approaches can be used: transabdominal and transvaginal. Another unique feature
      is that an understanding of developmental anatomy, which changes during
      pregnancy, is important. Two of the most basic yet important uses of ultrasound
      in the pregnant patient are to provide information concerning the gestational age
      of the pregnancy and the fetal heart rate. Ultrasound has a major role in the
      diagnosis and management of the patient with a suspected ectopic pregnancy.

PMID- 23137400
TI  - Gynecologic and other infections in pregnancy.
AB  - The treatment of gynecologic and other infections in obstetric patients involves
      consideration of the physiologic changes of pregnancy, the clinical implications
      of the infection for the patient as well as the fetus, and the safety of
      antimicrobials available for therapy. This article highlights the treatment of
      infections of the vagina, uterus, and urinary tract, with a focus on how therapy
      changes in obstetric patients. In addition, the emergency department management
      of other clinically important infections in pregnancy, such as those caused by
      the human immunodeficiency virus, influenza viruses, methicillin-resistant
      Staphylococcus aureus, Parvovirus, Listeria, and others is reviewed.

PMID- 23137401
TI  - Nonobstetric abdominal pain and surgical emergencies in pregnancy.
AB  - The focus of this article is the evaluation and management of pregnant patients
      with nonobstetric abdominal pain and surgical emergencies. The anatomic and
      physiologic changes that occur during pregnancy can cause difficulties in
      interpreting patients' signs and symptoms in emergency departments. This article
      reviews some of the common causes of nonobstetric abdominal pain and surgical
      emergencies that present to emergency departments and discusses some of the
      literature surrounding the use of imaging modalities during pregnancy. After a
      review of these changes and their causes, imaging modalities that can be used for
      the assessment are discussed.

PMID- 23137402
TI  - Hypertension and pregnancy.
AB  - Hypertension in pregnancy is increasing in prevalence and incidence and its
      treatment becoming more commonplace. Associated complications of pregnancy,
      including end-organ damage, preeclampsia, eclampsia, and postpartum eclampsia,
      are leading sources of maternal and fetal morbidity and mortality, requiring an
      emergency physician to become proficient with their identification and treatment.
      This article reviews hypertension in pregnancy as it relates to outcomes, with
      special emphasis on preeclampsia, eclampsia, and postpartum eclampsia.

PMID- 23137403
TI  - Complications in late pregnancy.
AB  - Complications of late pregnancy are managed infrequently in the emergency
      department and, thus, can pose a challenge when the emergency physician
      encounters acute presentations. An expert understanding of the anatomic and
      physiologic changes and possible complications of late pregnancy is vital to
      ensure proper evaluation and care for both mother and fetus. This article focuses
      on the late pregnancy issues that the emergency physician will face, from the
      bleeding and instability of abruptio placentae to the wide spectrum of
      complications and management strategies encountered with preterm labor.

PMID- 23137404
TI  - Trauma in pregnancy.
AB  - The treatment of pregnant patients with traumatic injuries requires knowledge of
      the fundamentals of general trauma management as well as the specific anatomic
      and physiologic changes brought about by pregnancy. This article provides a
      review of the spectrum of trauma prevention and treatment in pregnant women, from
      counseling strategies that can be used during any emergency department visit to a
      step-by-step evaluation protocol for patients with trauma during pregnancy and
      the severe injuries that might be encountered by providers during the treatment
      of these women, including maternal cardiopulmonary arrest and the perimortem
      cesarean section.

PMID- 23137405
TI  - Cardiovascular disasters in pregnancy.
AB  - Cardiovascular emergencies in pregnancy are rare but often catastrophic. This
      article reviews the diagnosis and management of venous thromboembolism, aortic
      dissection, acquired heart disease and cardiomyopathy, acute myocardial
      infarction, and cardiac dysrhythmias in the setting of pregnancy. It also reviews
      updated resuscitation guidelines for cardiac arrest and perimortem cesarean
      section.

PMID- 23137406
TI  - Precipitous and difficult deliveries.
AB  - Any delivery in the emergency department is considered a precipitous birth and is
      an anxiety-producing event. Many deliveries proceed without incident. However,
      the emergency physician must be prepared for several dreaded scenarios, such as
      nuchal cord, shoulder dystocia, and breech birth. This article reviews the
      basics, complications, and management of such deliveries.

PMID- 23137407
TI  - Obstetric toxicology: teratogens.
AB  - The emergency physician frequently encounters women who seek care because of
      pregnancy- and nonpregnancy-related complaints. Many medications are safe for use
      during pregnancy, including several that are listed as potential teratogens based
      on the Food and Drug Administration's (FDA) pregnancy classification; but it is
      important that the emergency physician know and recognize which drugs can be
      given in pregnancy and which drugs are absolutely contraindicated. Expert
      resources should be identified and used because the FDA's classification of drugs
      based on pregnancy risk does not represent the most up-to-date or accurate
      assessment of a drug's safety.

PMID- 23137408
TI  - Emergency evaluation and management of vaginal bleeding in the nonpregnant
      patient.
AB  - Evaluation of the nonpregnant patient presenting to the emergency department with
      vaginal bleeding requires the emergency physician to be aware of the potential
      for a variety of underlying causes. Patients with vaginal bleeding may have non
      life-threatening problems such as fibroids, endometriosis, or treatable sexually
      transmitted diseases such as gonorrhea and chlamydial infection. However, care
      must be taken to differentiate these from more serious causes of pelvic pain and
      bleeding such as ectopic pregnancy, hemorrhagic cyst, ovarian torsion, and rare
      complications from fibroids such as intraperitoneal hemorrhage. Abnormal bleeding
      unrelated to structural problems could have an anovulatory or ovulatory cause.

PMID- 23137409
TI  - Geriatric gynecology.
AB  - Most postmenopausal vaginal bleeding is benign; however, it merits diagnostic
      evaluation by transvaginal ultrasound or endometrial biopsy after emergency
      department evaluation. Patients and physicians may treat menopausal symptoms with
      hormone replacement therapy or other agents, such as venlafaxine or gabapentin.
      Hormone replacement therapy, when initiated close to the start of menopause and
      continued at the lowest possible dose for the shortest possible duration, carries
      less risk than previously believed. Pelvic organ prolapse affects millions of
      women and may contribute to poor body image and difficulty with urinary,
      gastrointestinal, and sexual function. Treatment options include Kegel exercises,
      pessaries, and surgery.

PMID- 23137410
TI  - Foreward: obstetric and gynecological emergencies.

PMID- 23137411
TI  - Obstetric and gynecologic emergencies. Preface.

PMID- 23137412
TI  - Use of the dipeptidyl peptidase-4 inhibitor  linagliptin  in combination therapy
      for type 2 diabetes.
AB  - INTRODUCTION: Most patients with type 2 diabetes mellitus (T2DM) are prescribed
      multiple medications - typically more than one for glycemic control alone, and
      others for the management of lipids and hypertension. Within a few years
      following diagnosis, many patients progress beyond an initial starting regimen of
      metformin and/or sulfonylurea in order to maintain glycemic control. With the
      broad selection of antidiabetes medications available today, the choice of which
      agents to add when progressing from monotherapy to combination therapy has led to
      much discussion on how to best tailor a treatment regimen to the individual
      patient's needs. AREAS COVERED: The aim of this paper is to review the literature
      describing the use of linagliptin as a component of combination therapy for the
      treatment of T2DM. Literature searches were conducted to retrieve articles
      reporting on linagliptin clinical trial data. For comparison of safety and
      efficacy, studies of linagliptin as monotherapy were included. EXPERT OPINION:
      Dipeptidyl peptidase-4 inhibitors are used across all stages of treatment, from
      monotherapy to dual or triple therapy regimens for glycemic control. Linagliptin
      has been studied in combination with the most commonly used classes of
      antihyperglycemic medications, with demonstrated efficacy and a safety profile
      comparable to placebo.

PMID- 23137413
TI  - Genetic testing in patients with acute coronary syndrome undergoing percutaneous
      coronary intervention: a cost-effectiveness analysis.
AB  - BACKGROUND: The CYP2C19 genotype is a predictor of adverse cardiovascular events
      in acute coronary syndrome (ACS) patients undergoing percutaneous coronary
      intervention (PCI) treated with clopidogrel. OBJECTIVES: We aimed to evaluate the
      cost-effectiveness of a CYP2C19*2 genotype-guided strategy of antiplatelet
      therapy in ACS patients undergoing PCI, compared with two 'no testing' strategies
      (empiric clopidogrel or prasugrel). METHODS: We developed a Markov model to
      compare three strategies. The model captured adverse cardiovascular events and
      antiplatelet-related complications. Costs were expressed in 2010 US dollars and
      estimated using diagnosis-related group codes and Medicare reimbursement rates.
      The net wholesale price for prasugrel was estimated as $5.45 per day. A generic
      estimate for clopidogrel of $1.00 per day was used and genetic testing was
      assumed to cost $500. RESULTS: Base case analyses demonstrated little difference
      between treatment strategies. The genetic testing-guided strategy yielded the
      most QALYs and was the least costly. Over 15 months, total costs were $18 lower
      with a gain of 0.004 QALY in the genotype-guided strategy compared with empiric
      clopidogrel, and $899 lower with a gain of 0.0005 QALY compared with empiric
      prasugrel. The strongest predictor of the preferred strategy was the relative
      risk of thrombotic events in carriers compared with wild-type individuals treated
      with clopidogrel. Above a 47% increased risk, a genotype-guided strategy was the
      dominant strategy. Above a clopidogrel cost of $3.96 per day, genetic testing was
      no longer dominant but remained cost-effective. CONCLUSIONS: Among ACS patients
      undergoing PCI, a genotype-guided strategy yields similar outcomes to empiric
      approaches to treatment, but is marginally less costly and more effective.

PMID- 23137414
TI  - Sleep disorders in Machado-Joseph disease: a dopamine transporter imaging study.
AB  - OBJECTIVES: Sleep disorders, especially restless legs syndrome (RLS) and rapid
      eye movement sleep behavior disorder (RBD), are common in spinocerebellar ataxia
      type 3 or Machado-Joseph disease (MJD), and a possible underlying dopaminergic
      dysfunction is implicated. This study assessed the relationship between sleep
      disorders in MJD and dopamine transporter (DAT) densities. PATIENTS AND METHODS:
      Twenty-two patients with MJD and twenty healthy subjects were enrolled in this
      study. MJD patients underwent clinical sleep evaluation and polysomnography.
      SPECT with [(99m)Tc]-TRODAT-1, was performed in all subjects. RESULTS: DAT
      densities were significantly reduced in MJD group when compared to controls. No
      significant correlation was found between DAT densities and RLS or RBD in MJD.
      CONCLUSION: Our study failed to demonstrate a clear correlation between sleep
      disorders and DAT densities in MJD patients, hence suggesting that extrastriatal
      and non-presynaptic dopamine pathways could be implicated in MJD-related sleep
      disorders.

PMID- 23137415
TI  - Transplantation of BMSCs expressing hVEGF165 /hBD3 promotes wound healing in rats
      with combined radiation-wound injury.
AB  - The combined radiation-wound injury is a refractory wound with decreased number
      or dysfunction of repairing cells and growth factors. This remains a challenge in
      clinical practice. The object of this study is to evaluate the therapeutic
      efficacy of a combination of human vascular endothelial growth factor 165
      (hVEGF(165)) and human beta-defensin 3 (hBD3) in the treatment of such wounds. A
      plasmid-carrying hVEGF(165) gene and hBD3 gene was used to transfect rat bone
      marrow-derived mesenchymal stem cells (BMSCs). The supernatant from the modified
      BMSCs significantly promoted the proliferation and cell migration of human
      endothelial cells and it also inhibited the growth of bacteria and fungus,
      demonstrating the successful expression of the transfected genes. The
      hVEGF(165)/hBD3-modified BMSCs were then injected into the sites of combined
      radiation-wound injury on rats. It demonstrated that wound-healing time was
      shortened significantly in the treated rats. The granulation tissue
      formation/maturation, skin appendage regeneration and collagen deposition were
      also improved significantly. Strong expression of hVEGF(165) and hBD3 was
      detected in the wound surface at early stage of the healing. The results indicate
      that topical transplantation of hVEGF(165)/hBD3-modified BMSCs promoted wound
      healing, and this gene therapy strategy presents a promising approach in the
      treatment of refractory wounds such as the combined radiation-wound injury.

PMID- 23137416
TI  - The match between institutional elderly care management research and management
      challenges - a systematic literature review.
AB  - BACKGROUND: Elderly care practice and its management together with policy and
      research play a crucial role in responding to increasing challenges in
      institutional care for elderly people. Successful dialogue between these is
      necessary. The purpose of this systematic literature review is to compare how
      institutional elderly care management research meets the care challenges
      currently emphasized in international long-term care policy documents. METHODS:
      This paper was based on a systematic literature review. After screening 1971
      abstracts using inclusion/exclusion criteria, 58 refereed articles published
      between 2000 and 2010 remained for analysis. The articles were analyzed using
      theory-based content analysis by comparing the results to the framework based on
      analysis of international long-term care management policy documents. RESULTS:
      The current challenges of long-term care management identified from policy
      documents were Integrated Care Management, Productivity Management, Quality
      Management, Workforce Management and ICT Management. The research on
      institutional elderly care management responded somewhat to the challenges
      mentioned in policy documents. However, some of the challenges were studied
      broadly and some were paid only minor attention. Further, only few studies
      focused on the core items of challenges addressed in policy documents.
      CONCLUSIONS: Institutional care management research needs to focus more on
      challenges in integrated care, productivity, ICT and division of labor. Managers,
      researchers and policy-makers should assume more active collaborative roles in
      processes of research, policymaking and policy implementation. In addition
      managers' and policymakers' scientific literacy needs to be enhanced.

PMID- 23137417
TI  - Reduction of paraoxonase-1 activity may contribute the qualitative impairment of
      HDL particles in patients with type 2 diabetes.
AB  - AIMS: Cholesterol efflux with high-density lipoprotein (HDL) particles has an
      important role in the first step of reverse cholesterol transport (RCT). However,
      HDL function in type 2 diabetes has not been well investigated thoroughly. We
      measured cholesterol efflux in 36 patients with type 2 diabetes compared with 9
      controls without diabetes. METHODS: The HDL fraction was separated with
      polyacrylamide gel and recovered using the protein recovery system. Concentration
      adjusted HDL fraction was used to determine HDL-mediated cholesterol efflux
      (Efflux-hdl) from THP-1 derived macrophages. We measured paraoxonase-1 (PON 1)
      activity to determine antioxidation capacity, serum amyloid A protein (SAA) to
      determine inflammatory response, and carboxymethyl-lysin (CML) to determine
      antiglucoxidative capacity. RESULTS: Efflux-hdl demonstrated no correlation with
      plasma apoprotein A-1 (ApoA-I) or HDL-cholesterol in patients with diabetes. PON1
      activity in the patients' HDL fraction was positively correlated with Efflux-hdl
      (r=0.39, p=0.02), and showed a negative tendency with HbA1c levels (r=-0.28,
      p=0.10). SAA and CML levels did not demonstrate correlation with Efflux-hdl in
      patients with diabetes. CONCLUSION: We confirmed the functional changes in HDL
      particles in the patients. Efflux-hdl from macrophages was reduced depending upon
      the decrease in PON1 activity, which was inversely related to HbA1c levels.

PMID- 23137418
TI  - A single-stage approach to learning phonological categories: insights from
      Inuktitut.
AB  - To acquire one's native phonological system, language-specific phonological
      categories and relationships must be extracted from the input. The acquisition of
      the categories and relationships has each in its own right been the focus of
      intense research. However, it is remarkable that research on the acquisition of
      categories and the relations between them has proceeded, for the most part,
      independently of one another. We argue that this has led to the implicit view
      that phonological acquisition is a "two-stage" process: Phonetic categories are
      first acquired and then subsequently mapped onto abstract phoneme categories. We
      present simulations that suggest two problems with this view: First, the learner
      might mistake the phoneme-level categories for phonetic-level categories and thus
      be unable to learn the relationships between phonetic-level categories; on the
      other hand, the learner might construct inaccurate phonetic-level representations
      that prevent it from finding regular relations among them. We suggest an
      alternative conception of the phonological acquisition problem that sidesteps
      this apparent inevitability and acquires phonemic categories in a single stage.
      Using acoustic data from Inuktitut, we show that this model reliably converges on
      a set of phoneme-level categories and phonetic-level relations among
      subcategories, without making use of a lexicon.

PMID- 23137419
TI  - What is it?

PMID- 23137420
TI  - Is physician self-disclosure ever appropriate?

PMID- 23137422
TI  - A virtue ethics approach to framing troublesome diagnoses.

PMID- 23137421
TI  - When Diagnosis is a Double-Edged Sword.

PMID- 23137423
TI  - The american medical association code of medical ethics' opinions on disclosing
      diagnoses to patients.

PMID- 23137424
TI  - Ethical issues in the early diagnosis of Alzheimer disease.

PMID- 23137425
TI  - Patient-Centered Revisions to the DSM-5.

PMID- 23137426
TI  - Challenging diagnoses.

PMID- 23137427
TI  - A Physician's Guide to Social Security Disability Determinations.

PMID- 23137428
TI  - Medicalizing obesity: individual, economic, and medical consequences.

PMID- 23137429
TI  - The rise and impending fall of diagnosis as a marker of difference.

PMID- 23137430
TI  - The evolution of addiction medicine as a medical specialty.

PMID- 23137431
TI  - The Pharmaceutical Industry's Role in Defining Illness.

PMID- 23137432
TI  - About the contributors.

PMID- 23137433
TI  - Synthesis of novel mono and bis-indole conduritol derivatives and their
      alpha/beta-glycosidase inhibitory effects.
AB  - Here we synthesized four novel indole conduritol derivatives 1-4 for the first
      time in the literature and probed their biological activities with the alpha and
      beta-glucosidases. The compounds showed quite effective glucosidase inhibitory
      action. IC(50) values of the compounds were compared with the known glucosidase
      inhibitor acarbose and it was determined that newly synthesized indole
      conduritols had more powerful effect against beta-glucosidase in addition to
      exhibiting moderate influence against alpha-glucosidase. Our molecules thus
      constitute an important starting point for the design and exploitation of novel
      glucosidase inhibitors since glucosidase inhibitors have widespread applications
      in the treatment of diabetes, viral infections, lysosomal storage diseases and
      cancers.

PMID- 23137434
TI  - Development of 5-nitrothiazole derivatives: identification of leads against both
      replicative and latent Mycobacterium tuberculosis.
AB  - Twenty eight 5-nitrothiazole derivatives were synthesized and evaluated for in
      vitro activities against Mycobacterium tuberculosis (MTB), cytotoxicity against
      HEK 293T. Among the compounds, 5-nitro-N-(5-nitrothiazol-2-yl)furan-2-carboxamide
      (20) was found to be the most active compound in vitro with MICs of 5.48 MUM
      against log-phase culture of MTB and also non-toxic up to 100 MUM.

PMID- 23137435
TI  - Relationship between plasma high-mobility group box-1 levels and clinical
      outcomes of ischemic stroke.
AB  - PURPOSE: High-mobility group box-1 (HMGB1) is regarded as a central mediator of
      inflammation and involved in many inflammatory diseases. This study aimed to
      investigate impact of plasma HMGB1 level on 1-year clinical outcomes of ischemic
      stroke. METHODS: Plasma HMGB1 levels of 338 patients were quantified by enzyme
      linked immunosorbent assay. The end points were mortality and unfavorable outcome
      (modified Rankin Scale score>2) after 1 year. RESULTS: Plasma HMGB1 level emerged
      as an independent predictor of 1-year clinical outcomes. Its prognostic value was
      similar to National Institutes of Health Stroke Scale score's. It improved
      prognostic value of National Institutes of Health Stroke Scale score. CONCLUSION:
      Plasma HMGB1 level represents a novel biomarker for predicting 1-year clinical
      outcomes of ischemic stroke.

PMID- 23137436
TI  - Surgical cricothyrotomy in the wilderness: a case report.
AB  - Although the surgical cricothyrotomy procedure is used on combat casualties in
      the most challenging environments, we are unaware of any published report in the
      United States of surgical cricothyrotomy performed in a wilderness recreational
      setting. We describe a 31-year-old male rock climber who fell 24.4 m (80 feet),
      sustaining serious injuries and requiring rescue from the base of the cliff by a
      cave/cliff rescue team. Ultimately, a surgical cricothyrotomy proved necessary
      because of ongoing oropharyngeal bleeding, facial fractures creating an unstable
      airway, and the need to place the patient in the litter. The patient survived a
      prolonged and arduous evacuation. This report presents the management of the
      patient during the rescue and the challenges faced by the rescue team physician
      and others that led to the decision to perform an improvised surgical
      cricothyrotomy.

PMID- 23137437
TI  - Cholera gravis associated with acute renal failure in a traveler from Haiti to
      the United States.
AB  - Cholera is a gastroenteric disease caused by epidemic or pandemic Vibrio cholerae
      which still is responsible for over 100,000 annual deaths worldwide. Since
      October 2010, Haiti experienced a cholera outbreak affecting more than 300,000
      persons. Few imported cases related to the Haitian epidemic have been reported so
      far in the United States and Canada. We presented a patient who developed cholera
      gravis soon after arrival at New York City from Haiti. The patient needed
      admission to an Intensive Care Unit, for vigorous intravenous hydration,
      antibiotic therapy, and hemodialysis due to refractory oliguric renal failure.
      The patient was discharged the day 6 after admission and V. cholerae O1 was
      isolated from the stool culture. Cholera can be a life-threatening disease; early
      recognition based on travel history and clinical features is the corner stone for
      successful management.

PMID- 23137438
TI  - Angioedema in the emergency department: an evidence-based review.
AB  - Angioedema is the end result of a variety of pathophysiological processes
      resulting in transient, localized, nonpitting swelling of the subcutaneous layer
      of the skin or submucosal layer of the respiratory or gastrointestinal tracts. It
      is now generally accepted that the swelling is mediated by either histamine or
      bradykinin. Angioedema may result in severe upper airway compromise or-less
      commonly recognized-compromise in the gastrointestinal tract often associated
      with severe abdominal pain. A variety of new therapeutic options are becoming
      available for use in the United States that have the potential to greatly impact
      the management and outcomes for those with severe clinical manifestations. This
      review assesses the evidence on the causes and treatments of angioedema in the
      emergency department and reviews the new therapeutic options available for
      treatment of angioedema based on their effectiveness, price, and availability.

PMID- 23137439
TI  - Insight into the antimicrobial activities of coprisin isolated from the dung
      beetle, Copris tripartitus, revealed by structure-activity relationships.
AB  - The novel 43-residue, insect defensin-like peptide coprisin, isolated from the
      dung beetle, Copris tripartitus, is a potent antibiotic with bacterial cell
      selectivity, exhibiting antimicrobial activities against Gram-positive and Gram
      negative bacteria without exerting hemolytic activity against human erythrocytes.
      Tests against Staphylococcus aureus using fluorescent dye leakage and
      depolarization measurements showed that coprisin targets the bacterial cell
      membrane. To understand structure-activity relationships, we determined the three
      dimensional structure of coprisin in aqueous solution by nuclear magnetic
      resonance spectroscopy, which showed that coprisin has an amphipathic alpha
      helical structure from Ala(19) to Arg(28), and beta-sheets from Gly(31) to
      Gln(35) and Val(38) to Arg(42). Coprisin has electropositive regions formed by
      Arg(28), Lys(29), Lys(30), and Arg(42) and ITC results proved that coprisin and
      LPS have electrostatically driven interactions. Using measurements of nitric
      oxide release and inflammatory cytokine production, we provide the first
      verification of the anti-inflammatory activity and associated mechanism of an
      insect defensin, demonstrating that the anti-inflammatory actions of the defensin
      like peptide, coprisin, are initiated by suppressing the binding of LPS to toll
      like receptor 4, and subsequently inhibiting the phosphorylation of p38 mitogen
      activated protein kinase and nuclear translocation of NF-kB. In conclusion, we
      have demonstrated that an amphipathic helix and an electropositive surface in
      coprisin may play important roles in its effective interaction with bacterial
      cell membranes and, ultimately, in its high antibacterial activity and potent
      anti-inflammatory activity. In addition to elucidating the antimicrobial action
      of coprisin, this work may provide insight into the mechanism of action of insect
      defense systems.

PMID- 23137440
TI  - Prospective study of risk factors for suicidal behavior in individuals with
      anxiety disorders.
AB  - BACKGROUND: Anxiety disorders are very common and increase risk for suicide
      attempts. Little is known about predictors of increased risk specifically among
      individuals with anxiety disorders. The purpose of this study was to investigate
      whether specific anxiety disorders and other co-morbid psychiatric disorders,
      physical health, or work or social functioning increased the future likelihood of
      a suicide attempts among individuals with anxiety disorders. Method In this
      prospective study, 676 individuals with an anxiety disorder were followed for an
      average of 12 years. RESULTS: As hypothesized, we found that post-traumatic
      stress disorder, major depressive disorder (MDD), intermittent depressive
      disorder (IDD), epilepsy, pain, and poor work and social functioning all
      predicted a shorter time to a suicide attempt in univariate analyses. In
      multivariate analyses, baseline MDD and IDD were independent predictors of time
      to suicide attempt, even when controlling for a past history of suicide attempt.
      No specific anxiety disorder was an independent predictor of time to attempt in
      this anxiety-disordered sample. Adding baseline physical health variables and
      social functioning did not improve the ability of the model to predict time to
      suicide attempt. CONCLUSIONS: Mood disorders and past history of suicide attempts
      are the most powerful predictors of a future suicide attempt in this sample of
      individuals, all of whom have an anxiety disorder.

PMID- 23137441
TI  - Effects of a metabotropic glutamate receptor 5 positive allosteric modulator,
      CDPPB, on spatial learning task performance in rodents.
AB  - Metabotropic glutamate receptor 5 (mGlu5) has been implicated in a variety of
      learning and memory processes and is important for avoidance learning. The
      present studies used an mGlu5 receptor positive allosteric modulator, 3-cyano-N
      (1,3 diphenyl-1H-hyrazol-5-yl)benzamide (CDPPB), to characterize the importance
      of mGlu5 receptors in aversively- and appetitively-motivated spatial learning
      tasks (tasks in which the instrumental contingency involves discriminative cues
      that differ in spatial location). C57Bl/6 male mice were initially trained in the
      Barnes maze in the absence of drug. Subsequently, CDPPB (30mg/kg, i.p.),
      administered 20min prior to each of 3 daily reversal learning training sessions
      in the Barnes maze, significantly enhanced performance compared to vehicle
      treated controls and had a significant effect on search strategy. Mice treated
      with CDPPB also displayed significantly less perseverative behavior than control
      treated animals. In a second experiment, male Sprague-Dawley rats were trained in
      an appetitively-motivated, delayed alternation version of a T-maze. 30mg/kg CDPPB
      (s.c.), delivered 20min prior to each of 5 daily training sessions, enhanced the
      delay rats were able to withstand between the sample and choice portions of each
      T-maze trial. The present results emphasize the role of mGlu5 receptors in
      spatial learning tasks and support previous studies which report mGlu5 positive
      allosteric modulators can enhance learning in some tasks and may have potential
      as nootropic drugs.

PMID- 23137442
TI  - Integrin participates in the effect of thyroxine on plasma membrane in immature
      rat testis.
AB  - BACKGROUND: The secretory activity of Sertoli cells (SC) is dependent on ion
      channel functions and protein synthesis and is critical to ongoing
      spermatogenesis. The aim of this study was to investigate the mechanism of action
      associated with a non-metabolizable amino acid [14C]-MeAIB (alpha-(methyl
      amino)isobutyric acid) accumulation stimulated by T4 and the role of the integrin
      receptor in this event, and also to clarify whether the T4 effect on MeAIB
      accumulation and on Ca2+ influx culminates in cell secretion. METHODS: We have
      studied the rapid and plasma membrane initiated effects of T4 by using 45Ca2+
      uptake and [45C]-MeAIB accumulation assays, respectively. Thymidine incorporation
      into DNA was used to monitor nuclear activity and quinacrine to analyze the
      secretory activity on SC. RESULTS: The stimulation of MeAIB accumulation byT4
      appears to be mediated by the integrin receptor in the plasma membrane since
      tetrac and RGD peptide were able to nullify the effect of this hormone. In
      addition, T4 increases extracellular Ca2+ uptake and Ca2+ from intracellular
      stocks to enhance nuclear activity, but this genomic action seems not to
      influence SC secretion mediated by T4. Also, the cytoskeleton and CIC-3 chloride
      channel contribute to the membrane-associated responses of SC. CONCLUSIONS: T4
      integrin receptor activation ultimately determines the plasma membrane responses
      on amino acid transport in SC, but it is not involved in calcium influx, cell
      secretion or the nuclear effect of the hormone. GENERAL SIGNIFICANCE: The
      integrin receptor activation by T4 may take a role in plasma membrane processes
      involved in the male reproductive system.

PMID- 23137444
TI  - Changes to cervical cancer prevention guidelines: effects on screening among U.S.
      women ages 15-29.
AB  - OBJECTIVE: A shift toward later initiation of cervical cancer screening for women
      began in 2002. We generated national estimates of screening prevalence rates and
      guideline-consistent screening among U.S. women ages 15-29 before and after the
      first evidence-based recommendations for reduced cervical cancer screening.
      METHOD: We used National Survey of Family Growth data to compare self-reported
      cervical cancer screening in 2002 and 2006-2008, stratified by age (15-17, 18-20,
      21-29) and sexual activity. We also assessed receipt of guideline-consistent
      screening by selected demographic variables. RESULTS: Among females ages 15-17,
      the proportion screened decreased from 23% to 12%, and screening was
      significantly more likely to be guideline-consistent. Among females ages 18-20,
      24% were screened too early in 2006-2008, but among those not yet sexually
      active, screening declined to 8%, appropriately reflecting new guidelines. In
      multivariable analysis, private health insurance, pregnancy, and hormonal
      contraceptive use were associated with guideline-consistent screening among
      sexually-active women. CONCLUSION: Fewer adolescents were being screened before
      sexual initiation, representing newer guidelines. However, sexually-active young
      adult women also should have later screening initiation. Factors related to
      health care access contribute to receipt of screening. Monitoring and provider
      education are needed to improve guideline-consistent screening, as newer
      guidelines call for less screening.

PMID- 23137445
TI  - Objectively-measured neighborhood environments and leisure-time physical activity
      in Chinese urban elders.
AB  - OBJECTIVE: The built environment may impact on elders' ability to engage in
      leisure-time physical activity (LTPA). Environmental correlates of LTPA in older
      Chinese residents of ultra-dense cities are unknown. The main aim of this study
      was to identify the aspects of the neighborhood environment associated with LTPA
      of Chinese elders residing in an ultra-dense city and able to walk unassisted.
      METHODS: This study was conducted in Hong Kong in 2007-2008. We investigated the
      relationships of neighborhood environmental attributes (environmental audits)
      with LTPA (interviewer-administered questionnaire) in 484 elders able to walk
      unassisted and living in 32 neighborhoods stratified by socio-economic status and
      walkability. RESULTS: The amount of recreational walking was positively related
      to the availability of parks (e(b) = 1.03; 95% CI = 1.02, 1.05) and several other
      environmental attributes. The odds of non-participation in other LTPA (OLTPA)
      were related to availability of recreational facilities (ORs from 0.96 to 0.99)
      and infrastructure, aesthetics, and safety aspects of the neighborhood. These
      aspects also moderated the relationships of recreational facilities with non
      participation in OLTPA, being negative only in safe, aesthetically-pleasing
      locations with good infrastructure. CONCLUSIONS: Safe, aesthetically-pleasing,
      low-pollution neighborhoods with easy access to recreational and public
      facilities may facilitate the engagement in LTPA in Chinese urban elders able to
      walk unassisted.

PMID- 23137446
TI  - Synthesis, characterization and cytotoxicity of platinum(II)/palladium(II)
      complexes with 1,3-diaminopropane and 4-toluensulfonyl-L-amino acid dianion.
AB  - Eight novel platinum(II)/palladium(II) complexes with 1,3-dap and 4
      toluensulfonyl-l-amino acid dianion, [Pt(1,3-dap)(TsalaNO)].0.5H(2)O (1a),
      [Pt(1,3-dap)(TsvalNO)] (1b), [Pt(1,3-dap)(TspheNO)] (1c), [Pt(1,3-dap)(TsserNO)]
      (1d), [Pd(1,3-dap)(TsalaNO)].1.5H(2)O (2a), [Pd(1,3-dap)(TsvalNO)] (2b), [Pd(1,3
      dap)(TspheNO)] (2c) and [Pd(1,3-dap)(TsileNO)] (2d) have been synthesized and
      characterized by elemental analysis, IR, UV, (1)H NMR and mass spectrometry
      techniques. Crystal structure of the complex 1b has been determined by X-ray
      diffraction. The cytotoxicity was tested by MTT and SRB assays. The complexes (1a
      1d and 2a-2d) exert cytotoxicity against Bel-7402, HL-60, KB and BGC-823, but
      none of them is more active than cisplatin. The results suggest that metal ions,
      amino acids and aliphatic N-containing ligands have effect on cytotoxicity, while
      the IC(50) values do not show definite correlation with variation of them.

PMID- 23137447
TI  - Synthesis and characterization of copper(II) and zinc(II)-based potential
      chemotherapeutic compounds: their biological evaluation viz. DNA binding profile,
      cleavage and antimicrobial activity.
AB  - Metal-based cancer chemotherapeutic agents of the type [Cu(phen)TzCl(2)]H(2)O 1
      and [Zn(phen)(Tz)Cl(2).H(2)O] 2, where phen = 1,10-phenanthroline and Tz = 1,2,4
      triazole have been synthesized and characterized by various spectroscopic and
      analytical techniques. The structure of complex 1 was also determined by X-ray
      crystallography. The in vitro DNA binding studies of complexes 1 and 2 with CT
      DNA were carried out by various biophysical and molecular docking techniques.
      Both the complexes cleave supercoiled pBR322 DNA via hydrolytic pathway, as
      validated by T4 DNA ligase assay. Furthermore, both complexes exhibited
      significant antimicrobial activity. The results revealed that complex 1 has
      better prospectus to act as cancer chemotherapeutic candidate which warrants
      further in vitro and in vivo anticancer investigations.

PMID- 23137448
TI  - Fibrate-derived N-(methylsulfonyl)amides with antagonistic properties on
      PPARalpha.
AB  - The identification of novel PPAR ligands represents an attractive research to
      fully understand the complex biological pathways regulated by these receptors.
      Selective PPAR modulators, inverse agonists and antagonists of three PPAR
      isoforms could help to clarify biological effects on lipid and glucose
      homeostasis. Here we describe the identification of a group of N
      (methylsulfonyl)amides, derived from PPARalpha agonist carboxylic acids.
      Transactivation and FRET assay confirmed an antagonist behaviour on PPARalpha for
      some of these compounds, with submicromolar IC(50). A preliminary analysis on
      selectivity alpha/gamma revealed different profiles of inhibition or activation.

PMID- 23137449
TI  - Overlapping genetic codes for overlapping frameshifted genes in Testudines, and
      Lepidochelys olivacea as special case.
AB  - Mitochondrial genes code for additional proteins after +2 frameshifts by
      reassigning stops to code for amino acids, which defines overlapping genetic
      codes for overlapping genes. Turtles recode stops UAR -> Trp and AGR -> Lys (AGR 
      > Gly in the marine Olive Ridley turtle, Lepidochelys olivacea). In Lepidochelys
      the +2 frameshifted mitochondrial Cytb gene lacks stops, open reading frames from
      other genes code for unknown proteins, and for regular mitochondrial proteins
      after frameshifts according to the overlapping genetic code. Lepidochelys'
      inversion between proteins coded by regular and overlapping genetic codes
      substantiates the existence of overlap coding. ND4 differs among Lepidochelys
      mitochondrial genomes: it is regular in DQ486893; in NC_011516, the open reading
      frame codes for another protein, the regular ND4 protein is coded by the
      frameshifted sequence reassigning stops as in other turtles. These systematic
      patterns are incompatible with Genbank/sequencing errors and DNA decay. Random
      mixing of synonymous codons, conserving main frame coding properties, shows
      optimization of natural sequences for overlap coding; Ka/Ks analyses show high
      positive (directional) selection on overlapping genes. Tests based on circular
      genetic codes confirm programmed frameshifts in ND3 and ND4l genes, and predicted
      frameshift sites for overlap coding in Lepidochelys. Chelonian mitochondria adapt
      for overlapping gene expression: cloverleaf formation by antisense tRNAs with
      predicted anticodons matching stops coevolves with overlap coding; antisense
      tRNAs with predicted expanded anticodons (frameshift suppressor tRNAs) associate
      with frameshift-coding in ND3 and ND4l, a potential regulation of frameshifted
      overlap coding. Anaeroby perhaps switched between regular and overlap coding
      genes in Lepidochelys.

PMID- 23137450
TI  - Reaffirming our commitment to serve.

PMID- 23137451
TI  - Balancing practice economics with patient need.

PMID- 23137452
TI  - Patient advocacy for beginners.

PMID- 23137453
TI  - Enforcing patient copays.

PMID- 23137454
TI  - The underserved pathway-fostering medical student interest in the care of
      vulnerable populations.

PMID- 23137455
TI  - Learning to care for the underserved-making the most of opportunities in medical
      school.

PMID- 23137456
TI  - The AMA Code of Medical Ethics' Opinion on Physicians' Duty to the Poor.

PMID- 23137457
TI  - Diagnosis and treatment of community-acquired pneumonia in children and adults.

PMID- 23137458
TI  - Medical-legal partnerships.

PMID- 23137459
TI  - Student-run clinics-a short-term solution to a systemic problem.

PMID- 23137461
TI  - Catholic hospitals and the safety net.

PMID- 23137460
TI  - Beyond charity-social justice and health care.

PMID- 23137462
TI  - Rebuilding medicine.

PMID- 23137463
TI  - About the contributors.

PMID- 23137464
TI  - Outbreak of Salmonella Thompson in the Netherlands since July 2012.
AB  - An ongoing outbreak of salmonellosis due to Salmonella Thompson is affecting the
      Netherlands. Between 2 August and 19 October 2012, 866 cases were confirmed.
      Their median age was 44 years (range: 0-95 years), 63% were female and 36% were
      hospitalised. A matched case-control study suggested smoked salmon as the
      vehicle. Salmonella Thompson was confirmed in four of nine batches of smoked
      salmon from one producer. A recall of all concerned smoked salmon products was
      executed starting end of September.

PMID- 23137465
TI  - An invasive mosquito species Aedes albopictus found in the Czech Republic, 2012.
AB  - Between July and September 2012, seventeen larvae of the invasive mosquito
      species Aedes (Stegomyia) albopictus (Skuse) were discovered using 60 ovitraps at
      four study sites alongside two main road exits in South Moravia, Czech Republic.
      This is the first report of imported Ae. albopictus in the Czech Republic. The
      findings highlight the need for a regular surveillance programme to monitor this
      invasive species throughout western and central Europe.

PMID- 23137466
TI  - Sequence-based typing of Legionella pneumophila serogroup 1 clinical isolates
      from Belgium between 2000 and 2010.
AB  - Sequence-based typing (SBT) is a discriminatory method widely used to genotype
      Legionella pneumophila strains. A total of 86 clinical L. pneumophila serogroup 1
      (sg1) isolates, collected between January 2000 and December 2010 in the two
      Belgian National Reference Centres for Legionella pneumophila, were genotyped
      using the internationally standardised SBT protocol of the European Working Group
      for Legionella Infections (EWGLI). The isolates could be classified into 31
      different sequence types (ST, index of diversity: 0.879). The obtained STs were
      submitted to the EWGLI SBT-database for L. pneumophila. In our study, ST47
      (27.9%) and ST1 (19.8%) were the most frequently detected STs. The detected
      profiles were a combination of both frequently isolated and unique STs, and of
      both worldwide distributed and more local strains. Two STs, ST880 and ST881, were
      new to the EWGLI database. In conclusion, we characterised L. pneumophila sg1
      isolates with the SBT method, and created a Belgian profile database that will be
      useful for future epidemiological studies.

PMID- 23137469
TI  - Systemic problems and personal accountability.

PMID- 23137468
TI  - Self-rated health and later receipt of work-related benefits: evidence from the
      1970 British Cohort Study.
AB  - BACKGROUND: Long-term sickness absence (LTSA) is most commonly due to common
      mental disorders and symptom-based conditions. Relatively little research has
      examined individual, as opposed to occupational, risk factors for LTSA.
      Individual appraisal of the workplace has been considered in several studies but
      self-rated health has more often been examined as a consequence of, rather than
      as a risk factor for, sickness absence. We aimed to study the association between
      self-rated health and later LTSA. METHOD: We used data from the 1970 British
      Cohort Study (BCS70). LTSA was defined as being in receipt of Incapacity Benefit
      (IB)/Severe Disablement Allowance (SDA) at age 34. The mother rated the
      participant's overall health at age 16; the participants self-rated at age 30.
      Reports of psychological and somatic symptoms were available at age 16; data on
      major health conditions were available at age 30. RESULTS: Analyses were
      restricted to those working, studying or caring for children at age 30 (n = 14
      105). One hundred and fifty-six (1.1%) were receiving IB or SDA by age 34. After
      adjustment for social class at birth, educational attainment, health conditions
      at age 30 and psychological and somatic symptoms at age 16, those who reported
      their health as poor had more than five times the odds of being long-term sick at
      age 34. CONCLUSIONS: The overall appraisal of an individual's health as poor,
      independent of any diagnosis, is a significant vulnerability factor for LTSA.

PMID- 23137470
TI  - After the apology-coping and recovery after errors.

PMID- 23137471
TI  - Labeling an adverse drug event "preventable".

PMID- 23137472
TI  - The problem with hand-offs.

PMID- 23137473
TI  - Medical ethics and retail clinics.

PMID- 23137474
TI  - Improvement science-a curricular imperative.

PMID- 23137475
TI  - The AMA Code of Medical Ethics' Opinions on Patient Safety.

PMID- 23137476
TI  - Medical error and individual accountability.

PMID- 23137477
TI  - Open-source health care software.

PMID- 23137478
TI  - The jury is still out on health courts.

PMID- 23137479
TI  - Patient safety organizations are step 1; data sharing is step 2.

PMID- 23137480
TI  - Resolving harmful medical mistakes-is there a role for forgiveness?

PMID- 23137481
TI  - Learning to Care about Patient Safety.

PMID- 23137482
TI  - Never events? Well, hardly ever.

PMID- 23137483
TI  - About the contributors.

PMID- 23137484
TI  - Interactivity in prosodic representations in children.
AB  - The aim of this study was to determine, using speech error and articulatory
      analyses, whether the binary distinction between iambs and trochees should be
      extended to include additional prosodic subcategories. Adults, children who are
      normally developing, and children with specific language impairment (SLI)
      participated. Children with SLI were included because they exhibit prosodic and
      motor deficits. Children, especially those with SLI, showed the expected increase
      in omission errors in weak initial syllables. Movement patterning analyses
      revealed that speakers produced differentiated articulatory templates beyond the
      broad categories of iamb and trochee. Finally, weak-weak prosodic sequences that
      crossed word boundaries showed increased articulatory variability when compared
      with strong-weak alternations. The binary distinction between iamb and trochee
      may be insufficient, with additional systematic prosodic subcategories evident,
      even in young children with SLI. Findings support increased interactivity in
      language processing.

PMID- 23137485
TI  - ST93-Queensland community-acquired meticillin-resistant Staphylococcus aureus
      clone in France: outbreak in a scout camp and sporadic cases, July to August
      2012.

PMID- 23137486
TI  - An unusual transmission event of Neisseria meningitidis serogroup W135 type 2a in
      a healthcare setting, England, 2012.

PMID- 23137489
TI  - Calcium supplementation and kidney stone risk in osteoporosis: a systematic
      literature review.
AB  - OBJECTIVES: This paper aims to examine the risk of nephrolithiasis in patients
      with osteoporosis and calcium supplementation. METHODS: This work is based on the
      systematic review of studies retrieved by a sensitive search strategy in Medline
      and Embase (1991-2010), and the Cochrane Central register of Controlled Trials
      (CENTRAL) up to 2010. The abstracts of the annual scientific meetings of the
      American College of Rheumatology (ACR) and the European League Against Rheumatism
      (EULAR) (2008-2010) were also examined. The selection criteria were the
      following: patients with osteoporosis, on calcium supplementation alone or
      associated with other treatments for osteoporosis. We measured the likelihood of
      developing kidney stones, renal colic, changes in urinary sediment and serum
      parameters. We selected systematic literature reviews, randomised clinical trials
      (RCT) and cohort studies. RESULTS: We included 10 studies, 8 RCT and 2 cohort
      studies of moderate quality. All patients had osteoporosis (>8.000 patients),
      they were mostly women with a mean age of 50-70 years. Daily calcium doses varied
      from 120 mg up to 1.500 mg, and treatment duration from 3 days to 3 years.
      Changes in urinary sediment were found, but in general they were not clinically
      relevant. No cases of nephrolitiasis were found in more than a half of the
      included studies. In total there were 3 cases of kidney stone, 2 urinary tract
      calcifications, 16 cases of nephrolithiasis or urolithiasis, 4 of haematuria and
      5 patients reporting kidney pain. CONCLUSIONS: According to our results, calcium
      supplements in the treatment of osteoporosis alone or in combination with another
      type of treatment does not significantly increase the risk of nephrolithiasis or
      renal colic.

PMID- 23137490
TI  - Language-specific noun bias: evidence from bilingual children.
AB  - Most evidence concerning cross-linguistic variation in noun bias, the
      preponderance of nouns in early expressive lexicons (Gentner, 1982), has come
      from comparisons of monolingual children acquiring different languages. Such
      designs are susceptible to a number of potential confounders, including group
      differences in developmental level and sociodemographic characteristics. The aim
      of this study was to quantify noun bias in bilingual Mandarin-English toddlers
      whose expressive lexicons in each language contained 50-300 words. Parents of
      fifty children (1;10-2;6) reported separately on their English and Mandarin
      expressive lexicons. The mean percentage of Mandarin nouns (38%) was
      significantly lower than the percentage of English nouns (54%) and was robust to
      analyses of twelve potential covariates. Analyses of the most frequently reported
      words suggested that lexical reduplication could be considered as a potential
      influence on vocabulary composition in future studies. Results suggest that
      characteristics of the input significantly shape early lexicons.

PMID- 23137491
TI  - Regionalization of ST-segment elevation myocardial infarction care: a task
      unfinished.

PMID- 23137492
TI  - Prognostic implications of troponin T and creatine kinase-MB elevation after
      coronary artery bypass grafting.

PMID- 23137493
TI  - Randomized controlled trial of ventricular elastic support therapy in the
      treatment of symptomatic heart failure: rationale and design.
AB  - BACKGROUND: Despite the current drug and device therapies, heart failure remains
      associated with high rates of disability, morbidity, and mortality. There is a
      need for newer therapies. One investigational approach is the use of ventricular
      support devices. These devices reduce ventricular wall stress leading to
      decreases in left ventricular (LV) volumes, dimensions, and mass. Ventricular
      support devices have been shown to reverse pathological ventricular remodeling,
      improve systolic function, and improve symptoms of heart failure. The Prospective
      Evaluation of Elastic Restraint to LESSen the effects of Heart Failure (PEERLESS
      HF) trial was designed to further evaluate the safety and efficacy of one such
      device, the HeartNet (Paracor Medical, Sunnyvale, CA). METHODS: The HeartNet is
      an elastic ventricular restraint device formed from nitinol and covered in
      silicone, implanted using a minimally invasive approach. The aim of this
      randomized controlled trial is to compare optimal heart failure drug and device
      therapy plus the HeartNet (treatment group) to optimal drug and device therapy
      alone (control group) in patients with advanced systolic heart failure (LV
      ejection fraction <=35% and LV end diastolic diameter <85 mm). Primary efficacy
      end points include the change in peak VO(2), quality of life score, and 6-minute
      hall walk distance from baseline to 6 months. The primary safety objective is to
      demonstrate noninferiority for all-cause mortality at 12 months. Planned
      enrollment is for 272 patients at approximately 35 centers in North America.
      CONCLUSIONS: The PEERLESS-HF trial will evaluate the safety and efficacy of
      ventricular elastic support in advanced systolic heart failure, advancing our
      knowledge of this investigational approach to heart failure therapy.

PMID- 23137494
TI  - The study of LoSmapimod treatment on inflammation and InfarCtSizE (SOLSTICE):
      design and rationale.
AB  - The p38 mitogen-activated protein kinase (MAPK) is a nexus point in inflammation,
      sensing, and stimulating cytokine production and driving cell migration and
      death. In acute coronary syndromes, p38MAPK inhibition could stabilize ruptured
      atherosclerotic plaques, pacify active plaques, and improve microvascular
      function, thereby reducing infarct size and risk of subsequent cardiac events.
      The SOLSTICE trial is randomized, double-blind, placebo-controlled, parallel
      group, multicenter phase 2a study of 535 patients that evaluates the safety and
      efficacy of losmapimod (GW856553), a potent oral p38MAPK inhibitor, vs placebo in
      patients with non-ST-segment elevation myocardial infarction expected to undergo
      an invasive strategy. The coprimary end points are reduction in high-sensitivity
      C-reactive protein at 12 weeks and reduction in infarct size as assessed by
      troponin area under the curve at 72 hours. A key secondary end point is 72-hour
      and 12-week B-type natriuretic peptide levels as a measure of cardiac remodeling
      and ventricular strain. The primary safety assessments are serious and nonserious
      adverse events, results of liver function testing, and major adverse cardiac
      events. Cardiac magnetic resonance imaging (N = 117) and coronary flow reserve (N
      = 13) substudies will assess the effects of losmapimod on infarct size,
      myocardial function, and coronary vasoregulation. Information gained from the
      SOLSTICE trial will inform further testing of this agent in larger clinical
      trials.

PMID- 23137495
TI  - ABSORB II randomized controlled trial: a clinical evaluation to compare the
      safety, efficacy, and performance of the Absorb everolimus-eluting bioresorbable
      vascular scaffold system against the XIENCE everolimus-eluting coronary stent
      system in the treatment of subjects with ischemic heart disease caused by de novo
      native coronary artery lesions: rationale and study design.
AB  - BACKGROUND: Currently, no data are available on the direct comparison between the
      Absorb everolimus-eluting bioresorbable vascular scaffold (Absorb BVS) and
      conventional metallic drug-eluting stents. METHODS: The ABSORB II study is a
      randomized, active-controlled, single-blinded, multicenter clinical trial aiming
      to compare the second-generation Absorb BVS with the XIENCE everolimus-eluting
      metallic stent. Approximately 501 subjects will be enrolled on a 2:1
      randomization basis (Absorb BVS/XIENCE stent) in approximately 40 investigational
      sites across Europe and New Zealand. Treated lesions will be up to 2 de novo
      native coronary artery lesions, each located in different major epicardial
      vessels, all with an angiographic maximal luminal diameter between 2.25 and 3.8
      mm as estimated by online quantitative coronary angiography (QCA) and a lesion
      length of <=48 mm. Clinical follow-up is planned at 30 and 180 days and at 1, 2,
      and 3 years. All subjects will undergo coronary angiography, intravascular
      ultrasound (IVUS) and IVUS-virtual histology at baseline (pre-device and post
      device implantation) and at 2-year angiographic follow-up. The primary end point
      is superiority of the Absorb BVS vs XIENCE stent in terms of vasomotor reactivity
      of the treated segment at 2 years, defined as the QCA quantified change in the
      mean lumen diameter prenitrate and postnitrate administration. The coprimary end
      point is the noninferiority (reflex to superiority) of the QCA-derived minimum
      lumen diameter at 2 years postnitrate minus minimum lumen diameter postprocedure
      postnitrate by QCA. In addition, all subjects allocated to the Absorb BVS group
      will undergo multislice computed tomography imaging at 3 years. CONCLUSIONS: The
      ABSORB II randomized controlled trial (ClinicalTrials.gov NCT01425281) is
      designed to compare the safety, efficacy, and performance of Absorb BVS against
      the XIENCE everolimus-eluting stent in the treatment of de novo native coronary
      artery lesions.

PMID- 23137496
TI  - Cardiac conduction system disease after transcatheter aortic valve replacement.
AB  - Transcatheter aortic valve replacement (TAVR) is a rapidly-evolving technology
      for patients with severe, calcific aortic stenosis. Although these procedures
      lessen many of the risks and complications of open surgical aortic valve
      replacement, there remain challenges with TAVR including electrophysiologic
      complications. Among TAVR prostheses, rates of conduction abnormalities (CAs)
      vary from less than 10% to more than 50%, with up to one-third of patients
      requiring placement of a permanent pacemaker following TAVR. Several predictors
      of CAs have been identified related to device selection, baseline conduction
      defects, and anatomical considerations. Current data support the hypothesis that
      CAs result primarily from mechanical compression of the specialized conduction
      system by the device, although other factors may be involved. Such abnormalities
      can arise immediately during the procedure or as late as several days after
      implantation, and can be transient or permanent. Currently, there are no clinical
      tools to identify patients at highest risk for CAs post-TAVR, or to predict the
      course of CAs in patients who experience them. Early data suggest outcomes may be
      worse in high-risk patients, and further studies are needed to identify these
      patients so as to minimize electrophysiologic complications and determine
      appropriate monitoring in this expanding population.

PMID- 23137498
TI  - De Facto regionalization of care for ST-elevation myocardial infarction in
      Florida, 2001-2009.
AB  - ACC/AHA guidelines recommend STEMI patients receive percutaneous coronary
      intervention (PCI) at high volume hospitals performing >=400 procedures/year. The
      objective of this study was to evaluate changes in the organization and
      implementation of care for STEMI patients in Florida. We assessed trends and
      predictors of STEMI patients first hospitalized at high PCI volume hospitals in
      Florida from 2001-2009. This is the first study to examine statewide trends in
      hospital admission for all STEMI patients. We classified Florida hospitals by PCI
      volume (high, medium, low, non-PCI) for each quarter from January, 2001 through
      June, 2009. Using hospital discharge data, we determined the percent of STEMI
      patients who went to each type of hospital and analyzed multiple predictors. From
      2001-2009 the proportion of STEMI patients first hospitalized at high PCI volume
      hospitals rose from 62.4 to 89.7%, while admissions to non-PCI hospitals declined
      from 31% to 4.9%. Persistent barriers to high PCI volume hospital admission were
      age >=85 years (OR 0.56, 95% CI 0.50-0.62), female gender (OR 0.85, 95% CI 0.79
      0.91), and residence in a major metropolitan county. Through the efforts of local
      coalitions throughout Florida, by 2009 almost 90% of Florida STEMI patients were
      first admitted to high PCI volume hospitals. Greater hospital competition may
      explain lower admission rates to high PCI volume hospitals in major metropolitan
      counties. The age and gender disadvantage we observed requires further research
      to determine potential causes.

PMID- 23137497
TI  - Modulating peroxisome proliferator-activated receptors for therapeutic benefit?
      Biology, clinical experience, and future prospects.
AB  - Clinical trials of cardiovascular disease (CVD) prevention in patients with type
      2 diabetes mellitus primarily have been directed at the modification of a single
      major risk factor; however, in trials that enroll patients with and without
      diabetes, the absolute risk in CVD events remains higher in patients with
      diabetes. Efforts to reduce the macrovascular and microvascular residual risk
      have been directed toward a multifactorial CVD risk-factor modification;
      nonetheless, long-term complications remain high. Dual-peroxisome proliferator
      activated receptor (PPAR) alpha/gamma agonists may offer opportunities to lower
      macrovascular and microvascular complications of type 2 diabetes mellitus beyond
      the reductions achieved with conventional risk-factor modification. The
      information presented elucidates the differentiation of compound-specific vs
      class-effect properties of PPARs as the basis for future development of a new
      candidate molecule. Prior experience with thiazolidinediones, an approved class
      of PPARgamma agonists, and glitazars, investigational class of dual
      PPARalpha/gamma agonists, also provides important lessons about the risks and
      benefits of targeting a nuclear receptor while revealing some of the future
      challenges for regulatory approval.

PMID- 23137499
TI  - Incidence and clinical significance of cardiac biomarker elevation during stem
      cell mobilization, apheresis, and intramyocardial delivery: an analysis from
      ACT34-CMI.
AB  - BACKGROUND: Cell therapy is a promising therapeutic for a variety of
      cardiovascular conditions including refractory angina. Elevation of cardiac
      biomarkers during cell delivery has been frequently described, but the clinical
      implications have never been studied. METHODS: ACT34-CMI was a randomized double
      blind study assessing the use of intramyocardial delivery of autologous CD34(+)
      cells for the treatment of refractory angina. Patients (n = 167) underwent G-CSF
      mediated (5 MUg/[kg day] * 5 days) stem cell mobilization, apheresis, and
      intramyocardial injection of 1 * 10(5)/kg or 5 * 10(5)/kg CD34(+) cells or
      placebo. Troponin and creatinine kinase MB were assessed at baseline (n = 161),
      after cell mobilization and apheresis (n = 153 and 143, respectively), and post
      intramyocardial injection (n = 155 and 141, respectively). Major adverse cardiac
      events (MACE) included death, myocardial infarction, acute congestive heart
      failure, urgent revascularization, or sustained ventricular arrhythmia. RESULTS:
      Seven (4.3%) subjects had troponin above the upper limits of normal (ULN) at
      baseline. Thirty-four (22.2%) and 11 (7.2%) subjects had troponin levels > ULN or
      >3* ULN after cell mobilization and apheresis, whereas 72 (46.1%) and 39 (25.2%)
      subjects had troponin elevations > ULN or >3* ULN, respectively, after
      intramyocardial injections. Age, but no other preprocedural factors, was
      predictive of troponin elevation. Periprocedural troponin elevation was not
      associated with an increased risk of MACE during 1 year, especially in cell
      therapy-treated patients. CONCLUSIONS: Troponin elevation is common during stem
      cell harvesting and intramyocardial administration, is usually asymptomatic, and
      does not appear to be associated with long-term MACE in subjects undergoing stem
      cell mobilization and intramyocardial injection.

PMID- 23137500
TI  - Effect of older age on diagnostic and prognostic performance of high-sensitivity
      troponin T in patients presenting to an emergency department.
AB  - BACKGROUND: The effect of age on diagnostic and prognostic performance of high
      sensitivity cardiac troponin T (hs-cTnT) has not been addressed adequately, so
      far. METHODS: High-sensitivity cardiac troponin T was measured serially in
      patients with acute symptoms presenting to our emergency department. We tested
      the diagnostic and prognostic performance of baseline and serial hs-cTnT
      concentrations related to age in all consecutive patients with acute coronary
      syndrome (ACS) (n = 342) or hs-cTnT increases not due to ACS (n = 442). RESULTS:
      Prevalence of elevated hs-cTnT in the study population was higher among patients
      >=75 years compared with younger patients (89.1 % vs 73.3 %, hazard ratio [HR]
      1.2, P < .0001). Elevated hs-cTnT was more likely due to ACS in the younger
      patients (HR 1.4, P = .001) and conversely more frequently due to non-ACS
      conditions in the elderly patients (HR 1.3, P = .0001). Diagnostic performance of
      hs-cTnT using the 99th percentile was significantly superior in younger than in
      elderly patients (P < .0001). For receiver operating characteristic-optimized
      cutoffs, a trend to significance was found between younger and older patients
      (area under the curve 0.87 vs 0.79, P = .074), with higher sensitivities (98.2 %
      vs 72.6%) and negative predictive values (97.3% vs. 78.5%) for patients <75
      years. Moreover, receiver operating characteristic-optimized cutoff values for
      diagnosis of non-ST-segment elevation myocardial infarction were significantly
      higher in elderly patients (32.9 ng/L) compared with younger patients (12.9
      ng/L). The prognostic information of single and serial hs-cTnT measurements was
      comparably poor in both age groups, showing no better prognostic information to
      hs-cTnT measurement on presentation. CONCLUSIONS: Elevated hs-cTnT is more common
      in the elderly due to higher prevalence of non-ACS conditions and significantly
      impairs diagnostic performance in discriminating non-ST-segment elevation
      myocardial infarction.

PMID- 23137501
TI  - Relation of circulating MicroRNA-133a concentrations with myocardial damage and
      clinical prognosis in ST-elevation myocardial infarction.
AB  - BACKGROUND: Circulating microRNAs (miRs) have emerged as potential diagnostic
      markers in patients with myocardial infarction. Previous studies, however, were
      based on limited patient numbers and could not assess the relation of miRs to
      myocardial damage. Moreover, the prognostic value of miRs in ST-elevation
      myocardial infarction (STEMI) is unknown. The aims of this study were (1) to
      assess the relation between miR-133a and myocardial damage assessed by
      cardiovascular magnetic resonance (CMR) imaging and (2) to evaluate the
      prognostic value of miR-133a in reperfused STEMI. METHODS: MicroRNA-133a
      concentrations were determined in 216 consecutive patients with STEMI undergoing
      primary angioplasty less than 12 hours after symptom onset. Patients were
      categorized into 2 groups defined by the median miR-133a value on admission.
      Cardiovascular magnetic resonance was performed for assessment of infarct size,
      myocardial salvage, and microvascular obstruction. The primary clinical end point
      was the occurrence of major adverse cardiovascular events defined as a composite
      of death, reinfarction, and new congestive heart failure within 6 months after
      infarction. RESULTS: All prognostic relevant CMR markers (infarct size,
      microvascular obstruction, myocardial salvage index) showed significant
      correlations with circulating miR-133a concentrations (P < .001 for all).The
      strongest predictors of miR-133a concentrations were the time from symptom onset
      to reperfusion and the amount of the salvaged area at risk. Major adverse
      cardiovascular events occurred significantly more often in the miR-133a >= median
      group (9% vs 20%, P = .025). However, miR-133a concentrations were unable to
      independently predict clinical events. CONCLUSIONS: Elevated levels of
      circulating miR-133a in patients with STEMI are associated with decreased
      myocardial salvage, larger infarcts, and more pronounced reperfusion injury.
      Consequently, miR-133a concentrations can provide prognostic information but do
      not add independent prognostic information to traditional and CMR markers of
      clinical prognosis in a high-risk STEMI population.

PMID- 23137502
TI  - Erythropoietin treatment in patients with acute myocardial infarction: a meta
      analysis of randomized controlled trials.
AB  - BACKGROUND: In experimental models of acute myocardial infarction (AMI),
      erythropoietin (EPO) reduces infarct size and improves left ventricular (LV)
      function. However, in the clinical setting, the effect of EPO in AMI was unclear.
      We conducted a systematic review and meta-analysis of randomized controlled
      trials (RCTs) of EPO to explore the safety and therapeutic effects of EPO in
      patients with AMI. METHODS: We identified reports of RCTs comparing EPO to
      placebo for AMI in adult humans in PubMed, Cochrane Central Register of
      Controlled Trials, and EMBASE. Outcomes included all-cause mortality, major
      cardiovascular events, cardiac function by LV ejection fraction and infarct size.
      RESULTS: We included 13 articles of RCTs with data for 1,564 patients.
      Erythropoietin therapy did not improve LV ejection fraction (weighted mean
      difference [WMD] 0.33, 95% CI -1.90 to 1.24, P = .68) and had no effect on
      infarct size, as measured by cardiac magnetic resonance imaging (WMD -0.12, -2.16
      to 1.91, P = .90) or serum peak value of creatine kinase-MB (WMD -2.01, -25.70 to
      21.68, P = .87). Erythropoietin treatment did not decrease the risk of total
      adverse cardiac events (relative risk [RR] 1.02, 0.65-1.61, P = .92).
      Erythropoietin treatment also failed to decrease the risk of heart failure (RR,
      0.69, 0.27-1.72, P = .42) and all-cause mortality (RR 0.55, 0.22-1.33, P = .18).
      Moreover, EPO had no effect on the risk of stent thrombosis (RR, 0.69, 0.29-1.64,
      P = .40). CONCLUSION: Erythropoietin in patients with AMI seems to have no
      clinical benefit for heart function or reducing infarct size, cardiovascular
      events, and all-cause mortality. Erythropoietin may not be a choice for patients
      with AMI.

PMID- 23137503
TI  - Outcome and causes of renal deterioration evaluated by serial cystatin C
      measurements in acute coronary syndrome patients -- results from the PLATelet
      inhibition and patient Outcomes (PLATO) study.
AB  - BACKGROUND: To investigate if ticagrelor treatment and other clinical
      characteristics were associated with increased cystatin C concentrations and if a
      deterioration in estimated renal function was associated with worse outcome in
      patients with acute coronary syndromes (ACS). METHODS: Plasma cystatin C
      concentrations were determined within 24 hours of admission (baseline), at
      discharge, 1 month, and 6 months in the PLATO trial. The changes over time in
      relation to randomized treatment were analyzed by analysis of covariance. C
      statistics and the relative Integrated Discrimination Improvement of the cystatin
      C concentrations regarding the primary outcome (cardiovascular death or
      myocardial infarction) was evaluated by multivariable analysis including
      background characteristics and biomarkers: N-terminal-pro-B-type natriuretic
      peptide and Troponin I. RESULTS: Mean cystatin C concentrations in 2133
      ticagrelor- and 2162 clopidogrel-treated patients were at baseline (0.86 mg/L and
      0.86 mg/L), discharge (1.01 mg/L and 0.98 mg/L) (P < .0005), 1 month (1.00 mg/L
      and 0.98 mg/L) (P = .12), and 6 months (1.00 mg/L and 0.99 mg/L) (P = .17),
      respectively. Age, heart failure, and type of ACS were major determinants of the
      cystatin C concentration. c Statistics and the relative Integrated Discrimination
      Improvement of the primary outcome for the baseline cystatin C concentration were
      0.687 and 5.2%, compared to 0.684 and 4.5% at discharge (n = 4034) and 0.693 and
      5.1% at one month (n = 3096), respectively. CONCLUSIONS: Mean cystatin C
      concentrations increased in ACS patients, most importantly determined by age. The
      initial greater increase in ticagrelor-treated patients was not sustained over
      time. Risk prediction did not improve with serial measurements of renal markers.

PMID- 23137504
TI  - Randomized controlled trial comparing simultaneous versus optimized sequential
      interventricular stimulation during cardiac resynchronization therapy.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) reduces morbidity and
      mortality and improves symptoms in patients with systolic heart failure (HF) and
      ventricular dyssynchrony. This randomized, double-blind, controlled study
      evaluated whether optimizing the interventricular stimulating interval (V-V) to
      sequentially activate the ventricles is clinically better than simultaneous V-V
      stimulation during CRT. METHODS: Patients with New York Heart Association (NYHA)
      III or IV HF, meeting both CRT and implantable cardioverter-defibrillator
      indications, randomly received either simultaneous CRT or CRT with optimized V-V
      settings for 6 months. Patients also underwent echocardiography-guided
      atrioventricular delay optimization to maximize left ventricular filling. The V-V
      optimization involved minimizing the left ventricular septal to posterior wall
      motion delay during CRT. The primary objective was to demonstrate noninferiority
      using a clinical composite end point that included mortality, HF hospitalization,
      NYHA functional class, and patient global assessment. Secondary end points
      included changes in NYHA classification, 6-minute hall walk distance, quality of
      life, peak VO(2), and event-free survival. RESULTS: The composite score improved
      in 75 (64.7%) of 116 simultaneous patients and in 92 (75.4%) of 122 optimized
      patients (P < .001, for noninferiority). A prespecified test of superiority
      showed that more optimized patients improved (P = .03). New York Heart
      Association functional class improved in 58.0% of simultaneous patients versus
      75.0% of optimized patients (P = .01). No significant differences in exercise
      capacity, quality of life, peak VO(2), or HF-related event rate between the 2
      groups were observed. CONCLUSIONS: These findings demonstrate modest clinical
      benefit with optimized sequential V-V stimulation during CRT in patients with
      NYHA class III and IV HF. Optimizing V-V timing may provide an additional tool
      for increasing the proportion of patients who respond to CRT.

PMID- 23137505
TI  - The role of advanced glycation end-products and their receptor on outcome in
      heart failure patients with preserved and reduced ejection fraction.
AB  - INTRODUCTION: Advanced glycation end products (AGEs) are increased in patients
      with heart failure (HF). We studied the predictive value of plasma AGEs
      N(epsilon)-(carboxymethyl)lysine (CML), pentosidine, and the soluble form of its
      receptor (sRAGE) in a large HF population. METHODS: In 580 patients hospitalized
      with HF, plasma AGEs were measured before discharge when patients were clinically
      stable. Patients were followed for a period of 18 months. Primary end point was a
      composite of death and HF admissions. CML was determined by liquid chromatography
      mass spectrometry, pentosidine by high-performance liquid chromatography and
      sRAGE by sequential sandwich immunoassay. RESULTS: Mean age was 71 +/- 11 years,
      62% were men, and mean left ventricular ejection fraction was 0.32 +/- 0.14. At
      baseline, mean CML level was 2.16 +/- 0.73 MUmol/L, median pentosidine was 0.043
      (0.030-0.074) MUmol/L, and median sRAGE level was 2.92 (1.90-4.59) ng/mL. CML and
      pentosidine levels were independently related to the composite end-point (HR,
      1.20 per SD; 95% CI,1.05-1.37; P = .01 and HR, 1.15 per SD; 95% CI, 1.00-1.31; P
      = .045, respectively) and HF hospitalization (HR, 1.27 per SD; 95% CI, 1.10-1.48;
      P = .001 and HR, 1.27 per SD; 95% CI, 1.10-1.47; P = .001, respectively).
      Furthermore, CML levels were independently related to increased mortality (P =
      .006). Whereas sRAGE levels were univariately predictive for outcome, in
      multivariate models sRAGE did not reach statistical significance. DISCUSSION: In
      HF patients, both CML and pentosidine predict HF hospitalization and the combined
      primary end-point (mortality or HF-hospitalization), whereas sRAGE did not
      predict events. In addition, CML was significantly and independently associated
      with a higher risk for mortality.

PMID- 23137506
TI  - Is heart failure guideline adherence being underestimated? The impact of
      therapeutic contraindications.
AB  - BACKGROUND: Several studies based on claims data have reported underutilization
      of evidence-based heart failure (HF) therapies. The degree to which these
      estimates fail to account for therapeutic contraindications is unclear. METHODS:
      We identified patients with HF and left ventricular ejection fraction <=45% seen
      between January 1, 2010, and July 1, 2010, at a tertiary care Veterans Affairs
      Medical Center. Medical records were abstracted to evaluate utilization of and
      contraindications to beta-blocker, angiotensin-converting enzyme inhibitor,
      aldosterone antagonist, anticoagulation for atrial fibrillation, implantable
      cardioverter-defibrillator, and cardiac resynchronization therapies. RESULTS: Of
      the 178 patients with HF and an ejection fraction <=45%, 78 (44%) received every
      guideline-recommended therapy. After accounting for medical contraindications, 77
      (72%) of 107 patients received every guideline-recommended therapy. Adherence to
      recommendations for beta-blocker (98%), angiotensin-converting enzyme
      inhibitor/angiotensin blocker (95%), and anticoagulation (97%) were better than
      adherence to implantable cardioverter-defibrillator (82%), cardiac
      resynchronization therapy (59%), or aldosterone antagonist (51%) recommendations.
      In adjusted analysis, lower New York Heart Association functional class and care
      by a cardiologist were associated with improved guideline adherence (P < .001).
      CONCLUSIONS: Many patients with HF have therapeutic contraindications, and a
      failure to account for these may lead to a large underestimation of the true
      guideline adherence rates.

PMID- 23137507
TI  - Comprehensive geriatric assessment and hospital mortality among older adults with
      decompensated heart failure.
AB  - BACKGROUND: The aim of this study is to assess whether a simple comprehensive
      geriatric assessment (CGA) score predicts hospital mortality among very elderly
      patients admitted with heart failure (HF). METHODS: This is a prospective follow
      up of 581 individuals aged >=75 years admitted for decompensated HF to an acute
      geriatric unit from October 2006 to September 2009. A CGA score (range, 0-10) was
      constructed using baseline individual data on 5 domains: dependence in activities
      of daily living (Katz index), mobility (qualitative mobility scale), cognition
      (Mini-Mental State Examination), comorbidity (Charlson index), and number of
      prescribed medications. RESULTS: Mean age of patients was 85.8 +/- 5.8 years, 67%
      were women, and 75% had preserved ventricular function (ejection fraction >45%).
      Fifty percent of patients required assistance in >=1 activities of daily living,
      66% had mobility problems, 45% had cognitive impairment, the mean Charlson index
      was 3.97 +/- 3.01, and 36% had >7 medications prescribed. As a result, the mean
      CGA score was 4.8 +/- 2.2. Hospital mortality was 8.2%. In multivariate analysis,
      variables associated with hospital mortality included New York Heart Association
      functional class III (odds ratio [OR] 4.1, 95% CI 1.5-10.8), class IV (OR 19.6,
      95% CI 6.3-61), pulmonary edema on chest radiography (OR 3.0, 95% CI 1.3-6.6),
      renal failure (OR 2.8, 95% 1.2-6.2), and the CGA score (OR 1.2, 95% CI 1.02-1.4
      for each point of increment). The area under the receiver operating
      characteristic curve was 0.856 (95% CI 0.790-0.921), and the model classified
      93.4% of cases correctly. CONCLUSIONS: In our cohort of very old patients with
      HF, a simple CGA score predicts hospital mortality.

PMID- 23137508
TI  - Biomarkers in acutely decompensated heart failure with preserved or reduced
      ejection fraction.
AB  - BACKGROUND: Acute decompensated heart failure (ADHF) occurs with preserved (heart
      failure with preserved ejection fraction [HFpEF] >=50%) or reduced (heart failure
      with reduced ejection fraction [HFrEF] <50%) ejection fraction. Natriuretic
      peptide (NP) levels are lower in HFpEF than HFrEF. We hypothesized that lower NP
      levels in HFpEF may be associated with other differences in biomarkers,
      specifically, renin-angiotensin-aldosterone system (RAAS) activation, oxidative
      stress, and a biomarker that reflects collagen synthesis. METHODS: In this
      prespecified ancillary analysis of patients with ADHF enrolled in the Diuretic
      Optimization Strategies Evaluation study, clinical features and N-terminal pro-B
      type NP, cystatin C, plasma renin activity, aldosterone, oxidative stress (uric
      acid), and procollagen type III N-terminal peptide were compared in HFpEF and
      HFrEF at enrollment and 60-day follow-up. RESULTS: Compared with HFrEF (n = 219),
      HFpEF (n = 81) patients were older, heavier, more commonly female, less treated
      with RAAS antagonists, but with similar New York Heart Association class, jugular
      venous pressure, and edema severity. N-terminal pro-B-type NP was lower, and
      systolic blood pressure and cystatin C were higher in HFpEF. Despite higher
      systolic blood pressure and less RAAS antagonist use in HFpEF, plasma renin
      activity and aldosterone levels were similar in HFpEF and HFrEF as were uric acid
      and procollagen type III N-terminal peptide levels. Changes in biomarker levels
      from enrollment to 60 days were similar between HFrEF (n = 149) and HFpEF (n =
      50). CONCLUSION: Lower NP levels in decompensated HFpEF occur in association with
      similar ADHF severity, more impaired vascular and renal function but similar
      elevation of biomarkers that reflect RAAS activation, oxidative stress, and
      collagen synthesis as in HFrEF.

PMID- 23137509
TI  - Intramyocardial injection of bone marrow mononuclear cells in chronic myocardial
      ischemia patients after previous placebo injection improves myocardial perfusion
      and anginal symptoms: an intra-patient comparison.
AB  - BACKGROUND: We recently demonstrated in a randomized, double-blind, placebo
      controlled trial that intramyocardial bone marrow cell (BMC) injection is
      associated with improvements in myocardial perfusion and anginal symptoms in
      chronic myocardial ischemia patients. In the present study the results of the
      crossover phase of this trial, in which patients previously treated with placebo
      received autologous BMC injections are reported. This allows a unique intra
      patient comparison on the effect of BMC versus placebo injection with elimination
      of patient-related confounding factors. METHODS: In 16 patients (14 male, 64 +/-
      10 years), who previously received intramyocardial placebo injections in the
      setting of a randomized trial, 100 * 10(6) BMC were injected using the NOGA
      system. Canadian Cardiovascular Society angina score and quality of life were
      evaluated at baseline, 3 and 6 months. Tc-99m single photon emission computed
      tomography and magnetic resonance imaging were performed at baseline and 3 months
      to assess myocardial perfusion and left ventricular (LV) function. RESULTS:
      Canadian Cardiovascular Society score and quality of life improved significantly
      after BMC injection as compared to placebo (P = 0.01 and P = 0.02, respectively).
      Single photon emission computed tomography revealed a significant greater
      improvement (P = 0.03) in summed stress score after BMC injection as compared to
      placebo. LV end-systolic volume significantly decreased after BMC injection but
      not after placebo injection. LV end-diastolic volume and LV ejection fraction did
      not change. CONCLUSION: Intramyocardial BMC injection in patients with chronic
      myocardial ischemia who previously received intramyocardial placebo treatment
      resulted in significant improvement in angina symptoms and myocardial perfusion.
      These results confirm the outcome of our previously reported randomized trial.

PMID- 23137510
TI  - Troponin T is a better predictor than creatine kinase-MB of long-term mortality
      after coronary artery bypass graft surgery.
AB  - BACKGROUND: Elevations of creatine kinase-MB (CK-MB) and cardiac troponin T
      (cTnT) have an uncertain long-term prognostic value after coronary artery bypass
      graft (CABG) surgery. We aimed to test the hypothesis that CK-MB and cTnT are
      predictors of long-term survival after CABG and to assess which of these 2
      biomarkers is the better predictor. METHODS: A total of 1,350 consecutive
      patients undergoing isolated on-pump CABG had CK-MB and cTnT measured at 7, 20,
      and 44 hours, postoperatively. The end point was all-cause mortality, and during
      the median follow-up time of 6.1 years, 207 patients (15.3%) died. RESULTS: Both
      peak CK-MB and peak cTnT independently predicted long-term mortality (hazard
      ratio [HR] 1.003, 95% confidence interval [CI] 1.001-1.005, P = .007, and HR
      1.31, 95% CI 1.17-1.46, P <.001, respectively) when analyzed in separate
      multivariate Cox models, adjusting for baseline demographic characteristics and
      perioperative risk factors. However, when analyzed simultaneously in the same Cox
      model, cTnT was a significant predictor (HR 1.31, 95% CI 1.13-1.51, P <.001),
      whereas CK-MB was not (P = .99). Similar results were found when the biomarkers
      were analyzed together in a Cox model adjusting for European System for Cardiac
      Operative Risk Evaluation. The differences in mortality between the biomarker
      groups were consistent also when analyzing strict quartiles of peak values of CK
      MB and cTnT (P = .81 and P = .001, respectively). CONCLUSIONS: Both CK-MB and
      cTnT are predictors of mortality after CABG surgery; however, our data suggest
      that cTnT is a better predictor of long-term mortality after CABG surgery than CK
      MB.

PMID- 23137511
TI  - Soluble form of membrane attack complex independently predicts mortality and
      cardiovascular events in patients with ST-elevation myocardial infarction treated
      with primary percutaneous coronary intervention.
AB  - BACKGROUND: The complement system is an important mediator of inflammation, which
      plays a pivotal role in atherosclerosis and acute myocardial infarction (AMI).
      Animal studies suggest that activation of the complement cascade resulting in the
      formation of soluble membrane attack complex (sMAC), contributes to both
      atherosclerosis and plaque rupture and may be the direct cause of tissue damage
      related to ischemia/reperfusion injury. However clinical data of sMAC during an
      AMI is sparse. Accordingly the aim was to investigate the prognostic role of sMAC
      in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: We
      included 725 STEMI-patients admitted to a single, high-volume invasive heart
      centre, treated with primary percutaneous coronary intervention (PCI), from
      September 2006 to December 2008. Blood samples were drawn immediately before PCI.
      Plasma sMAC was measured using an in-house immunoassay. Endpoints were all-cause
      mortality (n = 62) and the combined endpoint (n = 122) of major cardiovascular
      events (MACE) defined as cardiovascular mortality and admission due recurrent AMI
      or heart failure. Follow-up time was 12 months. RESULTS: During 12 months of
      follow-up 62 patients died from all causes and 122 patients reached the combined
      end-point of MACE. Patients with high sMAC (>75th percentile) had increased risk
      of both all-cause mortality and MACE. Even after adjustment for confounding risk
      factors by Cox-regression analyses, high levels of sMAC remained an independent
      predictor of all-cause mortality (hazard ratio 1.81 [95% CI 1.06-3.06; P = .029])
      and MACE (hazard ratio 1.70 [95% CI 1.16-2.48; P = .006]). CONCLUSIONS: High
      plasma sMAC independently predicts all-cause mortality and MACE in STEMI-patients
      treated with PCI.

PMID- 23137512
TI  - Quality of life and chronic heart failure therapy guided by natriuretic peptides:
      results from the ProBNP Outpatient Tailored Chronic Heart Failure Therapy
      (PROTECT) study.
AB  - BACKGROUND: Heart failure (HF) treatment guided by amino-terminal pro-B type
      natriuretic peptide (NT-proBNP) may reduce cardiovascular event rates compared to
      standard-of-care (SOC) management. Comprehensive understanding regarding effect
      of NT-proBNP guided care on patient-reported quality of life (QOL) remains
      unknown. METHODS: One hundred fifty-one subjects with HF due to left ventricular
      systolic dysfunction were randomized to either SOC HF management or care with a
      goal to reduce NT-proBNP values <=1000 pg/mL. Effects of HF on QOL were assessed
      using the Minnesota Living with HF Questionnaire (MLHFQ) quarterly, with change
      (Delta) in score assessed across study procedures and as a function of outcome.
      RESULTS: Overall, baseline MLHFQ score was 30. Across study visits, QOL improved
      in both arms, but was more improved and sustained in the NT-proBNP arm (repeated
      measures P = .01); NT-proBNP patients showing greater reduction in MLHFQ score (
      10.0 vs -5.0; P = .05), particularly in the physical scale of the questionnaire.
      Baseline MLHFQ scores did not correlate with NT-proBNP; in contrast, ?MLHFQ
      scores modestly correlated with ?NT-proBNP values (rho = .234; P = .006) as did
      relative ? in MLHFQ score and NT-proBNP (rho = .253; P = .003). Considered in
      tertiles, less improvement in MLHFQ scores was associated with a higher rate of
      HF hospitalization, worsening HF, and cardiovascular death (P = .001).
      CONCLUSIONS: We describe novel associations between NT-proBNP concentrations and
      QOL scores among patients treated with biomarker guided care. Compared to SOC HF
      management, NT-proBNP guided care was associated with greater and more sustained
      improvement in QOL (Clinical Trial Registration:
      www.clinicaltrials.govNCT00351390).

PMID- 23137513
TI  - Clarification of the Responses of Mental Stress Induced Myocardial Ischemia to
      Escitalopram Treatment (REMIT) trial protocol.

PMID- 23137515
TI  - Interleukin-21 is increased in active systemic lupus erythematosus patients and
      contributes to the generation of plasma B cells.
AB  - OBJECTIVES: Excessive interleukin- (IL-) 21 production by T cells has been
      implicated in the pathogenesis of systemic lupus erythematosus (SLE). We explored
      the expression and function of IL-21 in human SLE. METHODS: IL-21 and IL-21
      receptor (IL-21R) expression was assessed by real-time PCR and flow cytometry in
      peripheral blood mononuclear cells (PBMCs) of SLE patients and healthy controls.
      PBMCs, purified CD19+CD27- naive and CD19+CD27+ memory B cells were stimulated
      with IL-21 and CpG-ODN2006 (TLR-9 agonist) to examine generation of memory and
      plasma (CD19+CD38highIgD-) B cells. Apoptosis was assessed by 7AAD staining.
      RESULTS: Active SLE patients had 4-fold higher IL-21 mRNA and increased levels of
      intracellular IL-21 in peripheral blood CD4+ T cells (mean+/-SD fluorescence
      intensity, 1.7+/-0.1 in active versus 0.9+/-0.3 in inactive SLE and controls,
      p=0.035). IL-21R mRNA was comparable between SLE and healthy controls.
      Stimulation of PBMCs with IL-21 increased the proportion of memory and plasma
      cells; addition of CpG-ODN2006 enhanced these effects. Both naive and memory B
      cells responded to IL-21/TLR-9 by increased generation of memory and plasma B
      cells, respectively; an anti-apoptotic effect was observed. In active SLE, PBMCs
      stimulation with IL-21 and/or CpG-ODN increased memory and plasma B cells,
      comparable to healthy controls. Addition of IL-21 to lupus autologous mixed
      lymphocyte cultures induced significant IgG production, and treatment with IL
      21R.Fc to block IL-21/IL-21R interaction reduced the proportion of plasma cells.
      CONCLUSIONS: Increased IL-21 may synergise with TLR-9 signalling and contributes
      to generation of plasma cells in active SLE patients.

PMID- 23137516
TI  - Identification of a hidden outbreak due to the spread of a VIM-3-producing,
      extensive drug-resistant Pseudomonas aeruginosa (XDRPA) clone at a regional
      hospital in Taiwan.
AB  - A review of the annual prevalence of Pseudomonas aeruginosa at a regional
      hospital in Taiwan revealed a significant increase in the incidence of extensive
      drug-resistant P. aeruginosa (XDRPA) from 2?1% in 2003 to 5?8% in 2007. The first
      XDRPA isolate was recovered in 2001 from the emergency ward. The widespread
      dissemination of XDRPA isolates to more than 10 other wards was discovered the
      following year. Six pulsotypes of 67 XDRPA isolates from 2006 onwards were
      identified and 91% were a single strain, suggesting the existence of a hidden
      outbreak. Prior to the recognition of the outbreak, the majority of cases were
      not considered to be healthcare-associated infections until molecular evidence
      was provided. A cohort measure was launched by the infection control
      practitioners that effectively controlled the outbreak. Patients with XDRPA were
      mostly referred from neighbouring long-term care facilities, which may have been
      the reservoir of the XDRPA clone.

PMID- 23137517
TI  - Structure of SAICAR synthetase from Pyrococcus horikoshii OT3: insights into
      thermal stability.
AB  - The first native crystal structure of Phosphoribosylaminoimidazole
      succinocarboxamide synthetase (SAICAR synthetase) from a hyperthermophilic
      organism Pyrococcus horikoshii OT3 was determined in two space groups H3 (Type-1:
      Resolution 2.35A) and in C222(1) (Type-2: Resolution 1.9A). Both are dimeric but
      Type-1 structure exhibited hexameric arrangement due to the presence of cadmium
      ions. A comparison has been made on the sequence and structures of all SAICAR
      synthetases to better understand the differences between mesophilic, thermophilic
      and hyperthermophilic SAICAR synthetases. These SAICAR synthetases are reasonably
      similar in sequence and three-dimensional structure; however, differences were
      visible only in the subtler details of percentage composition of the sequences,
      salt bridge interactions and non-polar contact areas.

PMID- 23137519
TI  - The engineer and the clinician: understanding the work output and troubleshooting
      of the HeartMate II rotary flow pump.

PMID- 23137520
TI  - Routine left atrial appendage ligation during cardiac surgery may prevent
      postoperative atrial fibrillation-related cerebrovascular accident.
AB  - OBJECTIVE: The aim of the study was to determine whether routine left atrial
      appendage ligation in cardiac surgery would reduce the risk of postoperative
      atrial fibrillation-related cerebrovascular accident. METHODS: We performed an
      institutional review board-approved, case-control, retrospective chart review of
      adult patients who underwent cardiac surgery by a single surgeon between January
      1, 2001, and December 31, 2010. Preoperative CHADS(2) score criteria were
      collected, and outcomes through postoperative day 30 were analyzed. RESULTS: A
      total of 2067 patients were reviewed. Propensity score matching was used to
      create matched groups based on left atrial appendage ligation, and 631 patients
      were matched in each group. Subjects with postoperative atrial fibrillation were
      2.4 times (95% confidence interval, 1.51-2.82) more likely to undergo valve
      surgery, 2.11 times (95% confidence interval, 1.56-2.86) more likely to be aged
      more than 75 years, and 1.36 times (95% confidence interval, 1.03-1.80) more
      likely to have undergone left atrial appendage ligation. In the left atrial
      appendage ligation group with postoperative atrial fibrillation (n = 145), there
      were zero subjects (0%) with a postoperative cardiovascular accident. In the non
      left atrial appendage ligation group with postoperative atrial fibrillation (n =
      115), there were 7 subjects (6.1%) with a postoperative cardiovascular accident
      (0.0% vs 6.1%, P = .003). CONCLUSIONS: Although postoperative atrial fibrillation
      remains a common complication of cardiac surgery, there was a significant
      decrease in the incidence of postoperative cerebrovascular accidents since
      routine ligation of the left atrial appendage was undertaken. This has been found
      to be a safe adjunct to a wide variety of cardiac procedures and therefore
      deserves further study by a larger randomized controlled trial.

PMID- 23137521
TI  - Outbreak of measles in Central and Eastern Cheshire, UK, October 2008-February
      2009.
AB  - We describe the largest outbreak of measles in Central and Eastern Cheshire
      (North West England) since the MMR vaccine was introduced in 1988, the majority
      of cases were not vaccinated and more than 20% of the cases belonged to the
      travelling community. Over 4 months,147 clinical cases of measles were notified
      locally to the Cheshire & Merseyside Health Protection Unit (CMHPU). Of these, 67
      (45.6%) were laboratory confirmed, 42 (28.6%) were negative, and one was
      equivocal, leaving 23 probable and 14 possible cases. The primary case was
      probably an 8-year-old unvaccinated travelling child, symptomatic on 1 October
      2008. Measles spread locally and within school-aged children until early February
      2009. Most of Central and Eastern Cheshire, including 23 educational institutions
      (playgroups, nurseries, primary schools, secondary schools, colleges), were
      affected, showing that there were enough susceptible/unvaccinated children to
      sustain an outbreak. Nearly a quarter of the confirmed cases (15/67, 22.4%) were
      aged <13 months and too young to be vaccinated under the UK immunization
      schedule. This outbreak is a reminder of the importance of achieving herd
      immunity to prevent spread and protect those at risk of severe illness or
      complications. There were no fatalities in this outbreak and no significant
      complications were reported.

PMID- 23137522
TI  - Expression and significance of vascular endothelial growth factor A and C in
      leukemia central nervous system metastasis.
AB  - Metastasis to the central nervous system (CNS) is an obstacle for leukemia
      treatment, the mechanisms of which remain to be elucidated. VEGF-A and VEGF-C are
      suspected to participate in this process. Paired of cerebrospinal fluid (CSF) and
      serum samples were collected from leukemia and control cases. Levels of VEGF-A
      and VEGF-C in both CSF (VEGF-ACSF, VEGF-CCSF) and serum (VEGF-ASerum, VEGF
      CSerum) were detected by ELISA. Our data show that higher levels of VEGF-ACSF are
      closely related to CNS leukemia (CNSL), and VEGF-ACSF may be a better predictor
      than the other risk factors elucidating the pathogenesis and development of CNSL.

PMID- 23137523
TI  - Molecular characterization of chromosomal band 5p15.33: a recurrent breakpoint
      region in mantle cell lymphoma involving the TERT-CLPTM1L locus.
AB  - Secondary chromosomal aberrations may contribute to the development of a
      malignant phenotype in mantle cell lymphoma. Chromosomal band 5p15.33 represents
      a new recurrent breakpoint in B-cell malignancies. We present a molecular
      cytogenetic study of 8 mantle cell lymphoma (MCL) cell lines and 23 patients with
      MCL to determine and characterize novel secondary aberrations. We detected new
      secondary recurrent rearrangements in all cell lines and in 7 patients and
      confirmed 5p15.33 as a recurrent breakpoint in 4 cell lines and one patient.
      Further molecular characterization by flow-FISH and quantitative RT-PCR suggest
      TERT and CLPTM1L as target genes of 5p15.33 rearrangements.

PMID- 23137524
TI  - Genotyping of two populations of Southern Baltic Sea trout Salmo trutta m. trutta
      using an Atlantic salmon derived SNP-array.
AB  - The sea trout (Salmo trutta m. trutta) is an anadromous, teleost fish species
      characterized by homing behaviour. The sea trout has considerable ecological and
      economic significance. It reproduces naturally in rivers flowing into, and is
      common in, the Baltic Sea. In Poland spawning aggregations occur in the Vistula
      River and the rivers of Pomerania. Two populations from the Vistula River (TW)
      and a Pomeranian river, the Slupia (TP) were mixed in the past by stocking. The
      main purpose of this study was an assessment of the applicability of the Atlantic
      salmon custom design Illumina iSelect SNP (Single Nucleotide Polymorphisms) array
      containing 15,225 markers for identification of genetic diversity between sea
      trout populations. A diagnostic panel of 39 SNPs with a mean FST=0.1298 was
      selected from a pool of 15,225. At each locus, minor allele frequency was higher
      than 0.01 and mean expected heterozygosity for TW and TP populations were 0.343
      and 0.271 respectively. Individuals tested were clustered in one of two groups
      which corresponded to their origins where the TW population was genetically more
      homogenous (membership coefficients ranked from 88.8% to 98.6%) while the TP
      population was more diverse (membership coefficients ranked from 53.8% to 98.5%).
      The results demonstrated the applicability of the Salmon 15K SNP-chip for
      determining the differences between Southern Baltic populations of the sea trout,
      a closely related salmonid species. 

PMID- 23137525
TI  - Test-retest reliability and developmental evolution of the 6-min walk test in
      Caucasian boys aged 5-12 years.
AB  - The 6-min walk test (6MWT) assesses functional capacity and has been used as
      outcome measure in therapeutic studies in childhood neuromuscular disorders. The
      objectives were to evaluate test-retest reliability of the 6MWT and to generate
      normative data for healthy boys aged 5-12 years. Ninety boys (mean age 8 years 10
      months) were recruited over four age subcategories (5-6, 7-8, 9-10, 11-12 years).
      Mean 6MWT distance and velocity (+/-standard deviation) for the total group were
      555.5+/-93 m and 92.6+/-16.6 m/min. The 6MWT distance increased significantly
      with age. Test-retest reliability (mean interval 12 days) was very high for the
      total group (ICC>0.95) and for all age subcategories (ICC>0.80) a moderately high
      reliability (ICC>0.75) was found from 3 min onwards for each age subcategory.
      There was a mean difference of 5.2 m between test and retest without systematic
      bias. The standard error of measurement and smallest detectable difference were
      20.7 and 57.4 m, respectively. These findings demonstrate the reliability of the
      6MWT in young children, underscore its evolution with age, and indicate that a
      shorter version of the test is also reliable.

PMID- 23137526
TI  - [Bariatric surgery in adolescents].
AB  - The increased prevalence of obesity in children and adolescents is becoming a
      public health problem. As in adults, obesity is associated with other
      comorbidities and their risks. This systematic review aims to summarize the
      implications of morbid obesity in adolescents, and identify the currently
      accepted treatments for its management. Various treatments such as lifestyle
      changes, drug therapy, and surgery are the classical therapeutic triad. This
      review attempts to clarify the role of each of the major treatments in terms of
      safety and efficacy. Although obesity surgery in adolescents remains
      controversial for some aspects, there is evidence that the lack of effective
      treatment can lead to serious medical consequences in the future. Gastric bypass
      and gastric banding techniques remain of choice, but the role of other currently
      more popular techniques, such as sleeve gastrectomy should be clarified.

PMID- 23137527
TI  - Shift work and cancer risk: potential mechanistic roles of circadian disruption,
      light at night, and sleep deprivation.
AB  - Shift work that includes a nighttime rotation has become an unavoidable attribute
      of today's 24-h society. The related disruption of the human circadian time
      organization leads in the short-term to an array of jet-lag-like symptoms, and in
      the long-run it may contribute to weight gain/obesity, metabolic syndrome/type II
      diabetes, and cardiovascular disease. Epidemiologic studies also suggest
      increased cancer risk, especially for breast cancer, in night and rotating female
      shift workers. If confirmed in more controlled and detailed studies, the
      carcinogenic effect of night and shift work will constitute additional serious
      medical, economic, and social problems for a substantial proportion of the
      working population. Here, we examine the possible multiple and interconnected
      cancer-promoting mechanisms as a consequence of shift work, i.e., repeated
      disruption of the circadian system, pineal hormone melatonin suppression by
      exposure to light at night, sleep-deprivation-caused impairment of the immune
      system, plus metabolic changes favoring obesity and generation of proinflammatory
      reactive oxygen species.

PMID- 23137528
TI  - Serum miR-21 levels in patients with dermatomyositis.

PMID- 23137529
TI  - Geographic variation and sociodemographic disparity in the use of oxaliplatin
      containing chemotherapy in patients with stage III colon cancer.
AB  - This study examined the geographic variation and sociodemographic disparities in
      the use of oxaliplatin chemotherapy, which has not been widely studied in the
      past. Our results suggest that chemotherapy use varies across geographic regions.
      Patterns of use that relate specifically to oxaliplatin-containing chemotherapy
      can inform providers and researchers how newer regimens are being used as
      standard chemotherapy in a real-world setting. BACKGROUND: According to the
      National Cancer Comprehensive Network (NCCN), oxaliplatin with 5-fluorouracil and
      leucovorin (5-FU/LV) is the recommended adjuvant chemotherapy for patients with
      resected stage III colon cancer. Age and race are considered strong predictors of
      chemotherapy receipt, whereas geographic disparity has received minimal
      attention. The purpose of this study was to examine geographic variation and
      sociodemographic disparity in the use of chemotherapy in patients with stage III
      colon cancer, focusing specifically on oxaliplatin. METHODS: A retrospective
      cohort of 4106 Medicare patients was identified from the Surveillance,
      Epidemiology and End Results (SEER)/Medicare linked database. Descriptive
      statistics show how oxaliplatin-containing chemotherapy was used in various
      geographic regions among different age and racial groups. Multiple logistic
      regression analysis was performed to examine the relationship between receipt of
      oxaliplatin-containing chemotherapy and geographic region while adjusting for
      other sociodemographic and tumor characteristics. RESULTS: Only 49% of the
      patients with stage III disease received adjuvant chemotherapy within 3 to 6
      months of colon cancer-specific surgery. Patients aged 66 to 70 years were 78%
      more likely to receive chemotherapy than were those aged 80 years and older
      (P<.001). Patients in less urban regions were approximately 42% less likely to
      receive oxaliplatin chemotherapy than those residing in a big metro region (odds
      ratio [OR], 0.58; P=.008). CONCLUSION: Chemotherapy use varies across geographic
      regions, especially for new chemotherapy drugs like oxaliplatin. Further research
      is needed to identify the causes of this geographic disparity and ways to provide
      high-quality cancer care to all patients according to their preferences and
      needs.

PMID- 23137530
TI  - New diagnosis of type A interrupted aortic arch at age 24 years.

PMID- 23137531
TI  - Cost-effectiveness of cardiovascular disease spending.

PMID- 23137532
TI  - Prognostic value of self-reported versus objectively measured functional capacity
      in patients with heart failure: results from the TIME-CHF (Trial of Intensified
      Versus Standard Medical Therapy in Elderly Patients with Congestive Heart
      Failure).

PMID- 23137533
TI  - Acute mitral stenosis after transcatheter aortic valve implantation.

PMID- 23137534
TI  - Role of leukotriene B4 receptor signaling in human preadipocyte differentiation.
AB  - We investigated the role of leukotriene B(4) (LTB(4))-leukotriene receptor (BLT)
      signaling in preadipocyte differentiation into mature adipocytes. Blockade of BLT
      signaling by treatment with lipoxygenase inhibitors, a BLT antagonist, and small
      interfering RNAs for BLTs in human and mouse preadipocytes isolated from adipose
      tissues showed acceleration of differentiation into mature adipocytes. DNA
      microarray analysis revealed regulation of transforming growth factor, beta
      induced 68 kDa (TGFBI) expression through the BLT signaling pathway during
      adipocyte differentiation. Knockdown of TGFBI also showed acceleration of
      preadipocyte differentiation. The LTB(4)-BLT signaling pathway may negatively
      regulate preadipocyte differentiation via induction of TGFBI expression as a rate
      limiting system to control adipocyte differentiation.

PMID- 23137535
TI  - Cloning, characterization and sub-cellular localization of gamma subunit of T
      complex protein-1 (chaperonin) from Leishmania donovani.
AB  - T-complex protein-1 (TCP1) complex, a chaperonin class of protein, ubiquitous in
      all genera of life, is involved in intracellular assembly and folding of various
      proteins. The gamma subunit of TCP1 complex (TCP1gamma), plays a pivotal role in
      the folding and assembly of cytoskeleton protein(s) as an individual or complexed
      with other subunits. Here, we report for the first time cloning, characterization
      and expression of the TCP1gamma of Leishmania donovani (LdTCP1gamma), the
      causative agent of Indian Kala-azar. Primary sequence analysis of LdTCP1gamma
      revealed the presence of all the characteristic features of TCP1gamma. However,
      leishmanial TCP1gamma represents a distinct kinetoplastid group, clustered in a
      separate branch of the phylogenic tree. LdTCP1gamma exhibited differential
      expression in different stages of promastigotes. The non-dividing stationary
      phase promastigotes exhibited 2.5-fold less expression of LdTCP1gamma as compared
      to rapidly dividing log phase parasites. The sub-cellular distribution of
      LdTCP1gamma was studied in log phase promastigotes by employing indirect
      immunofluorescence microscopy. The protein was present not only in cytoplasm but
      it was also localized in nucleus, peri-nuclear region, flagella, flagellar pocket
      and apical region. Co-localization of LdTCP1gamma with actin suggests that, this
      gene may have a role in maintaining the structural dynamics of cytoskeleton of
      parasite.

PMID- 23137536
TI  - MiR-186, miR-216b, miR-337-3p, and miR-760 cooperatively induce cellular
      senescence by targeting alpha subunit of protein kinase CKII in human colorectal
      cancer cells.
AB  - We previously demonstrated that downregulation of protein kinase CKII induces
      cellular senescence in human colon cancer HCT116 cells. To investigate the role
      of microRNAs (miRNAs) in CKII downregulation during senescence, we employed
      computational algorithms. Four miRNAs (miR-186, miR-216b, miR-337-3p, and miR
      760) were predicted to be miRNAs against CKIIalpha mRNA. Mimics of all four
      miRNAs jointly downregulated CKIIalpha expression in HCT116 cells. Reporter
      analysis and RT-PCR have suggested that these four miRNAs may stimulate
      degradation of CKIIalpha mRNA by targeting its 3' untranslated regions (UTRs).
      The four miRNA mimics increased senescent-associated beta-galactosidase (SA-beta
      gal) staining, p53 and p21(Cip1/WAF1) expression, and reactive oxygen species
      (ROS) production. In contrast, concomitant knockdown of the four miRNAs by
      antisense inhibitors increased the CKIIalpha protein level and suppressed CKII
      inhibition-mediated senescence. Finally, CKIIalpha overexpression antagonized
      senescence induced by the four miRNA mimics. Therefore, the present results show
      that miR-186, miR-216b, miR-337-3p, and miR-760 cooperatively promote cellular
      senescence through the p53-p21(Cip1/WAF1) pathway by CKII downregulation-mediated
      ROS production in HCT116 cells.

PMID- 23137537
TI  - BET bromodomain inhibition rescues erythropoietin differentiation of human
      erythroleukemia cell line UT7.
AB  - Malignant transformation is a multistep process requiring oncogenic activation,
      promoting cellular proliferation, frequently coupled to inhibition of terminal
      differentiation. Consequently, forcing the reengagement of terminal
      differentiation of transformed cells coupled or not with an inhibition of their
      proliferation is a putative therapeutic approach to counteracting tumorigenicity.
      UT7 is a human leukemic cell line able to grow in the presence of IL3, GM-CSF and
      Epo. This cell line has been widely used to study Epo-R/Epo signaling pathways
      but is a poor model for erythroid differentiation. We used the BET bromodomain
      inhibition drug JQ1 to target gene expression, including that of c-Myc. We have
      shown that only 2 days of JQ1 treatment was required to transitory inhibit Epo
      induced UT7 proliferation and to restore terminal erythroid differentiation. This
      study highlights the importance of a cellular erythroid cycle break mediated by c
      Myc inhibition before initiation of the erythropoiesis program and describes a
      new model for BET bromodomain inhibitor drug application.

PMID- 23137538
TI  - Crystal structure of the Candida albicans Kar3 kinesin motor domain fused to
      maltose-binding protein.
AB  - In the human fungal pathogen Candida albicans, the Kinesin-14 motor protein Kar3
      (CaKar3) is critical for normal mitotic division, nuclear fusion during mating,
      and morphogenic transition from the commensal yeast form to the virulent hyphal
      form. As a first step towards detailed characterization of this motor of
      potential medical significance, we have crystallized and determined the X-ray
      structure of the motor domain of CaKar3 as a maltose-binding protein (MBP)
      fusion. The structure shows strong conservation of overall motor domain topology
      to other Kar3 kinesins, but with some prominent differences in one of the motifs
      that compose the nucleotide-binding pocket and the surface charge distribution.
      The MBP and Kar3 modules are arranged such that MBP interacts with the Kar3 motor
      domain core at the same site where the neck linker of conventional kinesins docks
      during the "ATP state" of the mechanochemical cycle. This site differs from the
      Kar3 neck-core interface in the recent structure of the ScKar3Vik1 heterodimer.
      The position of MBP is also completely distinct from the Vik1 subunit in this
      complex. This may suggest that the site of MBP interaction on the CaKar3 motor
      domain provides an interface for the neck, or perhaps a partner subunit, at an
      intermediate state of its motile cycle that has not yet been observed for Kinesin
      14 motors.

PMID- 23137539
TI  - Rossmann-fold motifs can confer multiple functions to metabolic enzymes: RNA
      binding and ribonuclease activity of a UDP-glucose dehydrogenase.
AB  - Metabolic enzymes are usually characterized to have one specific function, and
      this is the case of UDP-glucose dehydrogenase that catalyzes the twofold NAD(+)
      dependent oxidation of UDP-glucose into UDP-glucuronic acid. We have determined
      that this enzyme is also capable of participating in other cellular processes.
      Here, we report that the bacterial UDP-glucose dehydrogenase (UgdG) from
      Sphingomonas elodea ATCC 31461, which provides UDP-glucuronic acid for the
      synthesis of the exopolysaccharide gellan, is not only able to bind RNA but also
      acts as a ribonuclease. The ribonucleolytic activity occurs independently of the
      presence of NAD(+) and the RNA binding site does not coincide with the NAD(+)
      binding region. We have also performed the kinetics of interaction between UgdG
      and RNA. Moreover, computer analysis reveals that the N- and C-terminal domains
      of UgdG share structural features with ancient mitochondrial ribonucleases named
      MAR. MARs are present in lower eukaryotic microorganisms, have a Rossmannoid-fold
      and belong to the isochorismatase superfamily. This observation reinforces that
      the Rossmann structural motifs found in NAD(+)-dependent dehydrogenases can have
      a dual function working as a nucleotide cofactor binding domain and as a
      ribonuclease.

PMID- 23137540
TI  - SIRT1 sensitizes hepatocellular carcinoma cells expressing hepatitis B virus X
      protein to oxidative stress-induced apoptosis.
AB  - We previously showed that SIRT1 deacetylase inhibits proliferation of
      hepatocellular carcinoma cells expressing hepatitis B virus (HBV) X protein
      (HBX), by destabilization of beta-catenin. Here, we report another role for SIRT1
      in HBX-mediated resistance to oxidative stress. Ectopic expression and enhanced
      activity of SIRT1 sensitize Hep3B cells stably expressing HBX to oxidative stress
      induced apoptosis. SIRT1 mutant analysis showed that nuclear localization of
      SIRT1 is not required for sensitization of oxidation-mediated apoptosis.
      Furthermore, ectopic expression of SIRT1 and treatment with resveratrol (a SIRT1
      activator) attenuated JNK phosphorylation, which is a prerequisite for resistance
      to oxidative stress-induced apoptosis. Conversely, suppression of SIRT1 activity
      with nicotinamide inhibited the effect of resveratrol on JNK phosphorylation,
      leading to restoration of resistance to oxidation-induced apoptosis. Taken
      together, these results suggest that up-regulation of SIRT1 under oxidative
      stress may be a therapeutic strategy for treatment of hepatocellular carcinoma
      cells related to HBV through inhibition of JNK activation.

PMID- 23137541
TI  - Recombinant expression and solution structure of antimicrobial peptide aurelin
      from jellyfish Aurelia aurita.
AB  - Aurelin is a 40-residue cationic antimicrobial peptide isolated from the mezoglea
      of a scyphoid jellyfish Aurelia aurita. Aurelin and its (15)N-labeled analogue
      were overexpressed in Escherichia coli and purified. Antimicrobial activity of
      the recombinant peptide was examined, and its spatial structure was studied by
      NMR spectroscopy. Aurelin represents a compact globule, enclosing one 3(10)-helix
      and two alpha-helical regions cross-linked by three disulfide bonds. The peptide
      binds to anionic lipid (POPC/DOPG, 3:1) vesicles even at physiological salt
      concentration, it does not interact with zwitterionic (POPC) vesicles and
      interacts with the DPC micelle surface with moderate affinity via two alpha
      helical regions. Although aurelin shows structural homology to the BgK and ShK
      toxins of sea anemones, its surface does not possess the "functional dyad"
      required for the high-affinity interaction with the K(+)-channels. The obtained
      data permit to correlate the modest antibacterial properties and membrane
      activity of aurelin.

PMID- 23137542
TI  - Preferential involvement of Na+/Ca2+ exchanger type-1 in the brain damage caused
      by transient focal cerebral ischemia in mice.
AB  - The Na(+)/Ca(2+) exchanger (NCX), an ion-transporter located in the plasma
      membrane of neuronal cells, contributes to intracellular Ca(2+) homeostasis.
      Within the brain, three isoforms (NCX1, NCX2, and NCX3) are widely distributed.
      However, it is not clear to what extent these isoforms are involved in ischemic
      brain damage in mammals. We therefore used genetically altered mice and isoform
      selective NCX inhibitors in a model of transient focal ischemia to investigate
      the role of each NCX isoform in ischemic brain damage. NCX isoform-mutant mice
      (NCX1(+/-), NCX2(+/-), and NCX3(+/-)) and wild-type mice were subjected to 90min
      of middle cerebral artery occlusion (MCAO) followed by 24h of reperfusion. One of
      three NCX inhibitors [SN-6, KB-R7943, or SEA0400 (3 or 10mgkg(-1), i.p.)] was
      administered to ddY mice at 30min before more prolonged (4-h) MCAO followed by
      24h of reperfusion. After transient MCAO reperfusion, the cerebral infarcts in
      NCX1(+/-) mice, but not those in NCX2(+/-) or NCX3(+/-) mice, were significantly
      smaller than those in wild-type mice. SN-6 and SEA0400, which are more selective
      for the NCX1 isoform, significantly reduced the infarct volume at 10mg/kg. In
      contrast, KB-R7943, which is more selective for NCX3, did not. These results
      suggest that the NCX1 isoform may act preferentially (vs. the NCX2 and NCX3
      isoforms) to exacerbate the cerebral damage caused by ischemic insult in mice,
      and that NCX1-selective inhibitors warrant investigation as a potential
      therapeutic agents for stroke.

PMID- 23137543
TI  - Cell cycle arrest and apoptosis, two alternative mechanisms for PMKT2 killer
      activity.
AB  - Pichia membranifaciens CYC 1086 secretes a unique 30kDa killer toxin (PMKT2) that
      inhibits a variety of spoilage yeasts and fungi of agronomical interest. The
      cytocidal effect of PMKT2 on Saccharomyces cerevisiae cells was studied.
      Metabolic events associated with the loss of S. cerevisiae viability caused by
      PMKT2 were qualitatively identical to those reported for K28 killer toxin
      activity, but different to those reported for PMKT. At higher doses, none of the
      cellular events accounting for the action of PMKT, the killer toxin secreted by
      P. membranifaciens CYC 1106, was observed for PMKT2. Potassium leakage, sodium
      influx and the decrease of intracellular pH were not among the primary effects of
      PMKT2. We report here that this protein is unable to form ion-permeable channels
      in liposome membranes, suggesting that channel formation is not the mechanism of
      cytotoxic action of PMKT2. Nevertheless, flow cytometry studies have revealed a
      cell cycle arrest at an early S-phase with an immature bud and pre-replicated 1n
      DNA content. By testing the sensitivity of cells arrested at different stages in
      the cell cycle, we hoped to identify the execution point for lethality more
      precisely. Cells arrested at the G1-phase by alpha-factor or arrested at G2-phase
      by the spindle poison methyl benzimidazol-2-yl-carbamate (MBC) were protected
      against the toxin. Cells released from the arrest in both cases were killed by
      PMKT2 at a similar rate. Nevertheless, cells released from MBC-arrest were able
      to grow for a short time, and then viability dropped rapidly. These findings
      suggest that cells released from G2-phase are initially able to divide, but die
      in the presence of PMKT2 after initiating the S-phase in a new cycle, adopting a
      terminal phenotype within that cycle. By contrast, low doses of PMKT and PMKT2
      were able to generate the same cellular response. The evidence presented here
      shows that treating yeast with low doses of PMKT2 leads to the typical
      membranous, cytoplasmic, mitochondrial and nuclear markers of apoptosis, namely,
      the production of reactive oxygen species, DNA strand breaks, metacaspase
      activation and cytochrome c release.

PMID- 23137544
TI  - Effects of high-mobility group box1 on cerebral angiogenesis and neurogenesis
      after intracerebral hemorrhage.
AB  - Neural stem cells, which reside mainly in the subventricular and subgranular
      zones of the hippocampus, can regenerate new neuroblasts after various brain
      insults. Aided by vascular remodeling, these new neuroblasts migrate long
      distances to injured brain regions. Studies have suggested that high-mobility
      group box1 (HMGB1), a nonhistone nuclear DNA-binding protein, may stimulate such
      remodeling in the late phase of some types of brain injury, but it is unclear
      whether this is true for intracerebral hemorrhage (ICH). Here we used a rat model
      of collagenase-induced ICH to determine whether HMGB1 can promote neurogenesis
      and angiogenesis in the late phase of injury. Daily administration of ethyl
      pyruvate, which inhibited HMGB1 expression, reduced the recovery of neurological
      function, decreased vascular endothelial growth factor (VEGF) and nerve growth
      factor (NGF) levels in the ipsilateral striatum, and decreased the numbers of 5
      bromo-2-deoxyuridine (BrdU)- and doublecortin (DCX)-positive cells around the
      hematoma. These findings suggest that HMGB1 may promote angiogenesis and
      neurogenesis in the late phase of ICH.

PMID- 23137545
TI  - Evidence for layer-specific differences in auditory corticocollicular neurons.
AB  - Recent data suggest that there may be distinct processing streams emanating from
      auditory cortical layers 5 and 6 that influence the auditory midbrain. To
      determine whether these projections have different physiological properties, we
      injected rhodamine-tagged latex tracer beads into the inferior colliculus of >30
      day-old mice to label these corticofugal cells. Whole-cell recordings were
      performed on 62 labeled cells to determine their basic electrophysiological
      properties and cells were filled with biocytin to determine their morphological
      characteristics. Layer 5 auditory corticocollicular cells have prominent I(h)
      mediated sag and rebound currents, have relatively sluggish time constants, and
      can generate calcium-dependent rhythmic bursts. In contrast, layer 6 auditory
      corticocollicular cells are non-bursting, do not demonstrate sag or rebound
      currents and have short time constants. Quantitative analysis of morphology
      showed that layer 6 cells are smaller, have a horizontal orientation, and have
      very long dendrites (>500 MUm) that branch profusely both near the soma distally
      near the pia. Layer 5 corticocollicular cells are large pyramidal cells with a
      long apical dendrite with most branching near the pial surface. The marked
      differences in physiological properties and dendritic arborization between
      neurons in layers 5 and 6 make it likely that each type plays a distinct role in
      controlling auditory information processing in the midbrain.

PMID- 23137546
TI  - Endogenous nitric oxide induces activation of apoptosis signal-regulating kinase
      1 via S-nitrosylation in rat hippocampus during cerebral ischemia-reperfusion.
AB  - Apoptosis signal-regulating kinase 1 (ASK1) is a general mediator of cell death
      in response to a variety of stimuli, including reactive oxygen species, tumor
      necrosis factor alpha, lipopolysaccharide, endoplasmic reticulum stress, calcium
      influx and ischemia. Here we reported ASK1 was activated by nitric oxide (NO)
      through S-nitrosylation during cerebral ischemia-reperfusion. The reagents that
      abrogate neuronal nitric oxide synthase (nNOS) activity such as nNOS inhibitor
      7NI and N-methyl-D-aspartate receptor antagonist MK801 prevented ASK1 activation
      via decreasing ASK1 S-nitrosylation. In HEK293 cells, over-expressed ASK1 could
      be S-nitrosylated by both exogenous and endogenous NO and Cys869 was identified
      as the site of ASK1 S-nitrosylation. S-nitrosylation increased the level of ASK1
      phosphorylation at Thr845, which represents ASK1 activation. Our results further
      confirmed that S-nitrosylation led to the increment of ASK1 dimerization. S
      nitrosylation of ASK1 also activated the downstream JNK signaling and JNK
      mediated nucleic pathway. The exogenous NO (SNP and GSNO) reversed the effect of
      endogenous NO by suppressing S-nitrosylation of ASK1 and exerted neuroprotection
      during ischemia-reperfusion. These results suggest that inhibiting ASK1 S
      nitrosylation may be a novel approach for stroke therapy.

PMID- 23137547
TI  - Rapid reduction of Cr(VI) coupling with efficient removal of total chromium in
      the coexistence of Zn(0) and silica gel.
AB  - The effect of silica gel on the efficiency enhancement of Zn(0) for the reduction
      of Cr(VI) and removal of total chromium was investigated in this study. The batch
      experiment was carried at 4 <= pH <= 10 with 50 MUM initial Cr(VI) concentration,
      and mass loading of 0-40 g/L for silica gel and 0-8 g/L for Zn(0). Results showed
      limited Cr(VI) reduction in the Zn(0)/H(2)O system, which was attributed to the
      formation of passivating films on the Zn(0) surface. However, a complete
      reduction of Cr(VI) by Zn(0) in the presence of silica gel could be achieved at
      the all tested pHs. The rate of Cr(VI) reduction was markedly enhanced with a pH
      decrease, an increase of silica gel or Zn(0) loading, and specific surface area
      of silica gel. Almost complete removal of total chromium was also observed,
      suggesting that Cr(III) yielded from the reduction of Cr(VI) was adsorbed onto
      the silica gel and ZnO surface or existed in Zn-Cr mixed oxides or other Zn-Cr co
      precipitates. The possible pathways for Cr(VI) reduction and total chromium
      removal were proposed in this study, revealing the potential mechanism
      responsible for the rapid reduction of Cr(VI) coupling with the efficient removal
      of total chromium in the coexistence of Zn(0) and silica gel.

PMID- 23137548
TI  - Metabolism of diclofenac in plants--hydroxylation is followed by glucose
      conjugation.
AB  - Pharmaceuticals from human or veterinary medication form a new class of
      micropollutants that poses a serious threat to our aquatic environment and its
      organisms. The intensively used nonsteroidal anti-inflammatory drug diclofenac is
      found in the environment worldwide due to its poor elimination during waste water
      treatment processes. In order to test phytoremediation as a tool for the removal
      of this drug from waste water, the uptake of the compound into plant tissues and
      its metabolic pathway was addressed using Hordeum vulgare (barley) and a hairy
      root cell culture of Armoracia rusticana (horse radish) as model species.
      Diclofenac is taken up by plants and undergoes rapid metabolization; already
      after 3h of exposure the drug and its metabolites could be detected in the plant
      tissues. Similar to its fate in mammalian cells the drug is activated in a phase
      I reaction resulting in the hydroxylated metabolite 4'OH-diclofenac which is
      conjugated subsequently in phase II to a glucopyranoside, a typical plant
      specific metabolite. After exposure to 10 and 100 MUM diclofenac a concentration
      dependent formation of the hydroxylated metabolite was observed, while the
      formation of the phase II metabolite OH-diclofenac glucopyranoside was not
      positively affected by the higher concentration. To our knowledge this is the
      first time these two human painkiller metabolites are shown to occur in plant
      tissues.

PMID- 23137549
TI  - Clinical impact of ki-67 labeling index in non-small cell lung cancer.
AB  - The ki-67 index is a marker of proliferation in malignant tumors. Studies from
      the period 2000 to 2012 on the prognostic and predictive value of ki-67 labeling
      index (LI) in non-small cell cancer (NSCLC) are reviewed. Twenty-eight studies
      reported on the prognostic value of ki-67 index with various endpoints. No
      consensus on the prognostic value of ki-67 LI was found among the published
      studies neither according to disease stage nor histological subtype. Comparison
      of studies is hampered by differences in patient populations, methodologies and
      cut-off values. Five studies explored the predictive value of ki-67 to
      chemotherapy and none revealed significant influence. Ki-67 index seems to be of
      prognostic influence in NSCLC although largely variable cut-off levels have been
      used in the various studies and standardization of methodology is required. The
      relative importance of ki-67 compared to newer biomarkers has not been explored.
      It is likely that a signature of several biomarkers in combination may be
      necessary to more sufficiently stratify patients to various treatment options
      than is currently possible, especially when it comes to the question of the
      optimal use of classical chemotherapy. A predictive impact of ki-67 to treatment
      in NSCLC remains unclear.

PMID- 23137550
TI  - Effects of chlorimuron ethyl on terrestrial and wetland plants: Levels of, and
      time to recovery following sublethal exposure.
AB  - Current pesticide registration guidelines call for short-term testing of plants;
      long-term effects on vegetative parts and reproduction remain untested. The aims
      of our study were to determine level of recovery and recovery times for plants
      exposed to the sulfonylurea herbicide chlorimuron ethyl using data collected from
      single species, dose-response greenhouse experiments. The nine terrestrial and
      eight wetland species tested showed variable levels of recovery and recovery
      timeframes. Many species (six terrestrial and five wetland) were vegetatively
      stunted at sublethal doses and were reproductively impaired. Full recovery did
      not occur at all doses and maximum recovery times varied from 3 to 15 weeks in
      this controlled environment. In a complex community, affected species may be
      displaced by tolerant species, through interspecific competition, before they
      fully recover. It is plausible that individual populations could be diminished or
      eliminated through reduced seedbank inputs (annuals and perennials) and asexual
      reproduction (perennials).

PMID- 23137551
TI  - COST: Cognitive State Test, a brief screening battery for Alzheimer disease in
      illiterate and literate patients.
AB  - BACKGROUND: The aim was to develop a brief screening battery, Cognitive State
      Test (COST), for detecting the presence of dementia in both illiterate and
      literate patients and to assess its validity and reliability. METHODS: COST is a
      cognitive screening tool that consists of almost all cognitive domains. It takes
      5-7 minutes to administer, and has a maximum score of 30. Data were obtained from
      114 healthy volunteers and 74 Alzheimer dementia (AD) patients. Subjects' age
      divided into two groups: A1: <65 years; and A2: >=65 years and their education
      level divided into three groups: E1: illiterate; E2: 1-5 years; and E3: >=6
      years. For assessing concurrent validity, total COST score was compared to the
      Clinical Dementia Rating (CDR), the Mini Mental State Examination (MMSE), the
      Montreal Cognitive Assessment (MoCA), and Basic Activities of Daily Living
      (BADL). Sensitivity and specificity were determined through a discriminant
      analysis using the Receiver Operating Characteristic (ROC) curves. Internal
      consistency was measured using Cronbach's coefficient alpha. RESULTS: For normal
      and AD subjects, mean age was 64.9+/-9.8 years (50 women and 64 men) and 67.2+/
      13.2 years (55 women and 19 men), respectively. Schooling ranged from 0-15 years
      (mean 5.7+/-4.2 and 3.3+/-3.8 years, respectively), and 21 and 37 subjects were
      illiterate, respectively. The COST significantly and positively correlated with
      MMSE and MoCA, and significantly and inversely correlated with CDR, the Geriatric
      Depression Scale (GDS), and BADL. In the E1, E2, and E3 education groups, the
      optimal cut-off points of COST chosen for diagnosis of AD were 23/24
      (sensitivity: 81%, specificity: 99%), 24/25 (sensitivity: 75%, specificity: 86%),
      and 26/27 (sensitivity: 77%, specificity: 84%), respectively. When illiterate and
      literate subjects were then pooled, the optimal cut-off score of COST was 24/25,
      which yielded a sensitivity of 81% and a specificity of 87%. Reliability of the
      COST was good (0.86). CONCLUSION: The COST is a valid and reliable screening
      battery for detection of dementia both in the illiterate and the literate
      Alzheimer patients.

PMID- 23137552
TI  - Pharmacological treatment of Gilles de la Tourette syndrome.
AB  - Pharmacological treatment is usually indicated in moderate to severe tics in
      psychosocial and/or functional impairment. Neuroleptics with D2 antagonistic
      activity remain the cornerstone of anti-tic therapy. Lack of randomized
      controlled clinical trials base therapeutic decisions mainly on clinical
      expertise and common sense. Recently, aripiprazole has emerged as the neuroleptic
      with the most advantageous efficacy/side effect ratio for treating tics. Yet, in
      non-responders to aripiprazole, many neuroleptic and non-neuroleptic drugs,
      including botulinum toxin injections, are available and often successful. Apart
      from conducting methodologically sound trials (which includes sufficiently long
      observation periods), future efforts in the field should test the combination of
      cognitive-behavioral therapy with drugs or of multi-drug therapy as well as the
      development of biomarkers (endophenotypes) to monitor and even predict treatment
      response.

PMID- 23137553
TI  - Effects of an experimental in situ diesel oil spill on the benthic community of
      unvegetated tidal flats in a subtropical estuary (Paranagua Bay, Brazil).
AB  - The effects of diesel oil on benthic associations from unvegetated tidal flats in
      a subtropical estuary were experimentally evaluated using a Multivariate Before
      and After/Control and Impact Model (M-BACI). Impacted treatments were contrasted
      with controls in 14 successive periods before and after the oil spill. An acute
      effect was recorded just after the impact, but the recovery to pre-disturbance
      population levels was extremely fast. The increase in the total density of the
      benthic community after the disturbance was the result of an increase in the
      densities of Heleobia australis, oligochaetes, and ostracods, observed in both
      impacted and control treatments, as a reflection of background variability and
      not the presence of the contaminant. The experimental spill had little influence
      on the biological descriptors of the benthic associations, which were resilient
      or tolerant to oil disturbance at the temporal (147 days) and spatial (cm2)
      scales used in the experiment.

PMID- 23137554
TI  - Distribution and sources of sedimentary organic matter in a tropical estuary,
      south west coast of India (Cochin estuary): a baseline study.
AB  - Surface sediments samples were collected from 9 stations of the Cochin estuary
      during the monsoon, post-monsoon and pre-monsoon seasons and were analyzed for
      grain size, total organic carbon (OC), total nitrogen (TN) and stable isotopic
      ratios of carbon (delta13C) and nitrogen (delta(15N) to identify major sources of
      organic matter in surface sediments. Sediment grain size is found to be the key
      factor influencing the organic matter accumulation in surface sediments. The
      delta13C values ranges from -27.50/00 to -21.70/00 in surface sediments with a
      gradual increase from inner part of the estuary to the seaward side that suggest
      an increasing contribution of marine autogenous organic matter towards the
      seaward side. The delta15N value varies between 3.10/00 and 6.70/00 and it
      exhibits complex spatial and seasonal distributions in the study area. It is
      found that the dynamic cycling of nitrogen through various biogeochemical and
      organic matter degradation processes modifies the OC/TN ratios and delta15N to a
      considerable degree. The fraction of terrestrial organic matter in the total
      organic matter pool ranges from 13% to 74% in the surface sediments as estimated
      by delta13C based two end member mixing model.

PMID- 23137555
TI  - Spread of Alsidium corallinum C. Ag. in a Tyrrhenian eutrophic lagoon dominated
      by opportunistic macroalgae.
AB  - In 2007, the Rhodophyceae Alsidium corallinum C. Ag., a marine taxon, bloomed in
      the eutrophic lagoon of Orbetello (Tuscany, Italy) for the first time, becoming
      the dominant species in spring and summer. In November, its biomass collapsed.
      The hypothesis examined in this study is that the bloom expressed a relatively
      low eutrophic level of the ecosystem after intense disposal of accumulated
      sedimentary organic matter (OM) by dystrophic processes in the two years
      preceding the bloom. To verify the hypothesis, we compared water physical
      chemical variables, sediment redox (Eh) and OM, and standing crops of macroalgae
      and seagrass from the database of routine monitoring between 2005 and 2008. We
      also used dissolved nutrient data obtained in 2007 and 2008, as well as data on
      chlorophyll and total suspended matter in the water column during the microalgal
      bloom of 2007, and C, N and P content in thalli of the Chlorophycea Chaetomorpha
      linum and the Rhodophyceae Gracilariopsis longissima and A. corallinum obtained
      in 2007. In 2007, unusually low values of dissolved inorganic nitrogen (DIN) were
      recorded. Combined with stable values of soluble reactive phosphorus (SRPs), low
      DIN led to a reduction of about one order of magnitude in the DIN:SRP atomic
      ratio with respect to the past and to 2008. G. longissima accumulated C, N and P
      more than the other species and A. corallinum proved to be less demanding.
      Sediment OM was lower in the autumn of years characterized by dystrophy,
      confirming that summer dystrophic events coincided with maximum energy
      dissipation in this ecosystem. However, as soon as OM and DIN values increased
      (2008), the vegetation shifted towards blooms of G. longissima and C. linum,
      while A. corallinum almost disappeared. The results sustain the hypothesis that
      the bloom of A. corallinum was due to a decline in DIN that limited G.
      longissima, and to intense turbidity of the water caused by microphytes that
      developed after the dystrophic event of summer 2006. The latter probably limited
      the development of C. linum, which could only develop at the edges of the lagoon.

PMID- 23137556
TI  - Three decades (1983-2010) of contaminant trends in East Greenland polar bears
      (Ursus maritimus). Part 2: brominated flame retardants.
AB  - Brominated flame retardants were determined in adipose tissues from 294 polar
      bears (Ursus maritimus) sampled in East Greenland in 23 of the 28years between
      1983 and 2010. Significant linear increases were found for sum polybrominated
      diphenyl ether (SigmaPBDE), BDE100, BDE153, and hexabromocyclododecane (HBCD).
      Average increases of 5.0% per year (range: 2.9-7.6%/year) were found for the
      subadult polar bears. BDE47 and BDE99 concentrations did not show a significant
      linear trend over time, but rather a significant non-linear trend peaking between
      2000 and 2004. The average SigmaPBDE concentrations increased 2.3 fold from
      25.0ng/g lw (95% C.I.: 15.3-34.7ng/g lw) in 1983-1986 to 58.5ng/g lw (95% C.I.:
      43.6-73.4ng/g lw) in 2006-2010. Similar but fewer statistically significant
      trends were found for adult females and adult males likely due to smaller sample
      size and years. Analyses of delta(15)N and delta(13)C stable isotopes in hair
      revealed no clear linear temporal trends in trophic level or carbon source,
      respectively, and non-linear trends differed among sex and age groups. These
      increasing concentrations of organobromine contaminants contribute to complex
      organohalogen mixture, already causing health effects to the East Greenland polar
      bears. 

PMID- 23137557
TI  - Outcomes and prognostic factors of survival after pulmonary resection for
      metastatic gastric cancer.
AB  - OBJECTIVES: Gastric cancer is the most common malignant tumour in Japan. Because
      gastric cancer metastases to the lung generally occur as lymphangitic
      carcinomatosis or numerous lesions, metastasectomy is rarely indicated.
      Therefore, the role of resectable pulmonary metastasectomy in gastric cancer is
      still unclear. The objective of this study was to determine the surgical outcomes
      and prognostic factors for survival after pulmonary resection of resectable
      metastatic gastric cancer. METHODS: The database of the Metastatic Lung Tumor
      Study Group of Japan was retrospectively reviewed. Between March 1980 and March
      2011, 3831 patients underwent pulmonary metastasectomy. Fifty-one patients
      undergoing surgery for metastatic gastric cancer were analysed, and the survival
      parameters and prognostic factors after pulmonary metastasectomy were determined.
      RESULTS: The median time to recurrence after lung resection was 6 months (range,
      0-29 months). The overall 5-year survival rate after pulmonary metastasectomy was
      28%, and the median survival time was 29 months. Both univariate and multivariate
      analysis found that a disease-free interval <12 months was a poor prognostic
      factor (P = 0.01, P = 0.04, respectively). For 43 patients with a disease-free
      interval >=12 months, the 5-year survival rate was 31%. CONCLUSIONS: While
      resectable pulmonary metastases from gastric cancer are rare, a relatively good
      surgical outcome is expected for selected patients with disease-free intervals
      longer than 12 months.

PMID- 23137558
TI  - Cryopreserved human allografts (homografts) for the management of graft
      infections in the ascending aortic position extending to the arch.
AB  - OBJECTIVES: The management of infected Dacron grafts in the ascending aortic
      position involving the aortic arch and aortic root remains a technical challenge.
      Total replacement of the infected graft material with cryopreserved homografts
      appears to be an effective treatment strategy for these patients. METHODS:
      Seventeen consecutive patients were operated on for infection of their ascending
      aortic graft where the aortic arch was also involved 26 +/- 33 months after
      initial surgery, in 70%, for type A aortic dissection (12 acute aortic dissection
      type A and 1 chronic aortic dissection type A). The aortic root was additionally
      affected in 14 patients. Computed tomography and echocardiography follow-up was
      performed in all patients. RESULTS: Hospital mortality was 24% (n = 4).
      Cardiopulmonary bypass and aortic cross-clamp times were 288 +/- 128 and 165 +/-
      78 min, respectively. In 14 patients, the aortic root was replaced. Hypothermic
      circulatory arrest was necessary in all patients (41 +/- 25 min) with additional
      cold selective antegrade cerebral perfusion in 14 (41 +/- 30 min). During follow
      up, 1 patient died due to a cerebral haemorrhage at 3 months and another at 4
      years, of pulmonary embolism. Two patients were successfully reoperated on for
      degeneration of the aortic valve at 16 and 94 months; 1 patient had an early
      degeneration of the homograft and needed re-replacement with a homograft. In 2
      other patients, a stent graft had to be placed to cover the distal anastomosis
      between the homograft and native aorta. In all others, recent follow-up revealed
      no degeneration of the implanted homografts. CONCLUSIONS: Surgery for infected
      Dacron grafts in the ascending aortic position with involvement of the arch can
      be performed with an acceptable perioperative mortality. In case of degeneration
      of the valve, reoperations can be performed with good results in experienced
      hands. Therefore, we consider the concept of complete explantation of all
      infected material and replacement with homografts a successful treatment
      strategy. Nevertheless, close follow-up of the patients is mandatory so as not to
      miss any degeneration or reinfection of the implanted grafts.

PMID- 23137559
TI  - Acute type A aortic dissection: significance of multiorgan malperfusion.
AB  - OBJECTIVES: Acute type A aortic dissection (AAAD) remains one of the most
      challenging diseases in cardiothoracic surgery, and despite numerous innovations,
      early mortality still remains high. The aim of this study was to review the
      Emilia-Romagna experience in the treatment of AAAD and to evaluate the effect of
      malperfusion on mortality and morbidity. METHODS: We examined data of 502
      patients between January 2000 and December 2008, from the Emilia-Romagna Regional
      Registry of AAAD. The mean age was 62.4 +/- 13 years and 66.5% were male. At
      presentation, various types of malperfusion syndromes (cerebral, cardiac, ileo
      femoral, renal, mesenteric and spinal cord) were present in 103 patients (20.5%;
      malperfusion [MPS] group). Three hundred ninety-nine patients (No-MPS group) did
      not have pre-operative malperfusion. Arterial access for cardiopulmonary bypass
      was usually via the femoral artery (81.9%), while the axillary artery was used
      only in 14.7%. The aortic repair was performed using the 'open technique' in 348
      patients (69.3%) and with aortic cross-clamping without circulatory arrest in 154
      patients (30.7%). RESULTS: Overall in-hospital mortality was 20.9%: 43.7% in the
      MPS group vs 15% in the No-MPS group (P = 0.001). The operative technique and the
      cannulation site did not influence post-operative outcomes. Multivariate
      regression analysis identified mesenteric (odds ratio [OR] 9.5, confidence
      interval [CI] 2.4-37.4; P = 0.0012), cardiac malperfusion (OR 3.7, CI 1.7-8.0; P
      < 0.0001) and shock (OR 2.1, CI 1.2-3.5; P = 0.007) as significant risk factors
      for in-hospital mortality after surgery for type A dissection. Patients who
      presented single-organ malperfusion had a mortality rate of 34.7%, which
      increased to 61.9% and to 85.7% if two or more than two organ systems were
      involved, respectively. CONCLUSIONS: The results of the surgical treatment of
      AAAD are acceptable and mainly influenced by patient's status at presentation.
      Malperfusion of more organ systems makes the prognosis unfavourable and immediate
      proximal aortic repair may be sub-optimal. In these situations, alternative
      management strategies should be considered.

PMID- 23137560
TI  - The future for partnership: view from the industry.

PMID- 23137561
TI  - Reply to Tavlasoglu et al.

PMID- 23137562
TI  - Off-pump correction of an apical pseudoaneurysm after transcatheter aortic valve
      implantation.

PMID- 23137563
TI  - In-hospital mortality and long-term survival after coronary artery bypass surgery
      in young patients.
AB  - OBJECTIVES: Coronary artery bypass graft (CABG) is performed for symptomatic and
      prognostic reasons. We aimed to determine the factors that contribute to in
      hospital mortality and long-term survival in young patients (aged less than 65)
      undergoing CABG. METHODS: A prospective database was retrospectively analysed and
      cross-correlated with the United Kingdom's Strategic Tracing Service to evaluate
      survival in patients under the age of 65, following isolated primary CABG.
      Univariate-, multivariate logistic with Cox regression- and neural network
      analyses were performed. RESULTS: Patients under the age of 65, who had undergone
      isolated CABG between April 1997 and March 2010 were studied;n = 5967. In
      hospital mortality was 1.1% and long-term mortality was 13.5%; median follow-up
      7.9 years. Multivariate analysis demonstrated that atrial fibrillation, 'urgent'
      operation status, postoperative creatinine kinase (CKMB), moderate or poor left
      ventricular (LV) function, and female sex were significant factors predicting in
      hospital mortality. Cox regression demonstrated that age, diabetes (oral and
      insulin controlled), moderate and poor LV function, cerebrovascular disease,
      dialysis, left internal mammary artery (LIMA) usage, postoperative CKMB, atrial
      fibrillation, 'urgent' operation status, and peripheral vascular disease were
      significant factors determining long-term survival. Radial artery use, off-pump
      surgery, composite arterial grating and graft number had no effect on in-hospital
      mortality or long-term survival. Neural network analysis confirmed the factors
      identified by logistic and Cox multivariate analysis. CONCLUSIONS: The risk
      factors for in-hospital mortality in patients under the age of 65 include
      postoperative CKMB, urgent operation status, LV function, female sex and atrial
      fibrillation. Significant factors determining long-term survival in the under-65
      age group include age, atrial fibrillation, diabetes (diet and insulin
      controlled), LV function, cerebrovascular disease, dialysis, LIMA usage, 'urgent'
      operation status, CKMB and peripheral vascular disease.

PMID- 23137564
TI  - Letter to the editor.

PMID- 23137565
TI  - Critical result communication response to Piva and Plebani: best practices for
      communicating critical values.

PMID- 23137566
TI  - Implication of breast cancer phenotype for patients with leptomeningeal
      carcinomatosis.
AB  - BACKGROUND: We aimed to study the implications of breast cancer (BC) subtypes for
      the development and prognosis of leptomeningeal carcinomatosis (LC). PATIENTS AND
      METHODS: Data from the breast cancer patients diagnosed with LC between 2005 and
      2010 were retrieved. Patients were classified in luminal A, B, HER2 positive and
      triple negative (TN) and their BC diagnosis, treatment, and outcome were analyzed
      according to each subtype. Pearson's chi-square and Fisher's exact test were used
      for categorical variables. Survival analyses were performed by Kaplan-Meier
      method and compared with the log-rank test. RESULTS: A total of 38 BC patients
      were identified, with a median age of 54.8 years (range 36-79). The proportion of
      luminal A, B, HER2 positive and TN was 18.4%, 31.6%, 26.3% and 23.7%,
      respectively. LC was the first evidence of metastatic disease in 5 BC patients.
      Twenty patients received the systemic chemotherapy, with 16 (80%) whole brain
      radiotherapy (WBRT). Nine patients received only WBRT. TN patients had the
      shorter interval between metastatic breast cancer diagnosis and the development
      of LC. Median survival after the diagnosis of LC (OSLC) was 2.6 months (range 1.2
      6.4), and did not differ across breast cancer subtypes. In univariate analysis,
      performance status (ECOG = 0-2) and chemotherapy were prognostic for OSLC, but
      only the treatment stood as an independent prognostic factor in multivariate
      analysis. CONCLUSIONS: Breast cancer subtype influences the timing of LC
      appearance, but not OSLC. Patients with LC from breast cancer should be offered
      systemic treatment, as it appears to associate with the improved outcome. New
      therapeutic strategy, including, targeted and intrathecal therapy are deserved
      for BC patients with LC.

PMID- 23137567
TI  - Anticancer mechanisms and clinical application of alkylphospholipids.
AB  - Synthetic alkylphospholipids (ALPs), such as edelfosine, miltefosine, perifosine,
      erucylphosphocholine and erufosine, represent a relatively new class of
      structurally related antitumor agents that act on cell membranes rather than on
      DNA. They selectively target proliferating (tumor) cells, inducing growth arrest
      and apoptosis, and are potent sensitizers of conventional chemo- and
      radiotherapy. ALPs easily insert in the outer leaflet of the plasma membrane and
      cross the membrane via an ATP-dependent CDC50a-containing 'flippase' complex (in
      carcinoma cells), or are internalized by lipid raft-dependent endocytosis (in
      lymphoma/leukemic cells). ALPs resist catabolic degradation, therefore accumulate
      in the cell and interfere with lipid-dependent survival signaling pathways,
      notably PI3K-Akt and Raf-Erk1/2, and de novo phospholipid biosynthesis. At the
      same time, stress pathways (e.g. stress-activated protein kinase/JNK) are
      activated to promote apoptosis. In many preclinical and clinical studies,
      perifosine was the most effective ALP, mainly because it inhibits Akt activity
      potently and consistently, also in vivo. This property is successfully exploited
      clinically in highly malignant tumors, such as multiple myeloma and
      neuroblastoma, in which a tyrosine kinase receptor/Akt pathway is amplified. In
      such cases, perifosine therapy is most effective in combination with conventional
      anticancer regimens or with rapamycin-type mTOR inhibitors, and may overcome
      resistance to these agents. This article is part of a Special Issue entitled
      Phospholipids and Phospholipid Metabolism.

PMID- 23137568
TI  - Coronary aneurysms in a child: an unusual presentation of pseudovasculitis.
AB  - Abnormalities of the coronary arteries in children are rare and Kawasaki disease
      is the most common cause of acquired coronary disease in a paediatric population.
      We report a case of a female child with coronary artery aneurysms and
      convulsions, who was diagnosed with Kawasaki disease. Due to systemic arterial
      hypertension and persistence of high inflammatory markers after treatment with
      high dose glucocorticoid and intravenous immunoglobulin, further investigation
      was performed and revealed a pheochromocytoma. Surgical removal led to
      normalization of blood pressure and laboratory parameters. Periodic
      echocardiography studies revealed progressive reduction of coronary aneurysms,
      with complete normalisation after 8 months. This is the first case described of
      coronary aneurysms presenting as a pseudovasculitis syndrome associated with
      pheochromocytoma.

PMID- 23137569
TI  - An apparent homozygous deletion in maltase-glucoamylase, a lesson in the
      evolution of SNP arrays.
AB  - Single nucleotide polymorphism (SNP) arrays possess clinical potential due to
      their high throughput capacity, sensitivity and versatility. We used such an
      array to perform a genome-wide SNP analysis of a patient with a multi-system
      undiagnosed disease involving peripheral neuropathies and food intolerances. The
      patient had a homozygous deletion within the gene encoding maltase-glucoamylase
      (MGAM), an intestinal starch digestion enzyme, predicting absence of enzyme
      activity and potential starch indigestion. We then performed validation testing
      using a functional MGAM analysis that involved starch ingestion followed by
      measuring blood glucose and insulin levels as well as hydrogen breath levels.
      Gastrointestinal tissue was also obtained via endoscopy and immunohistochemical
      staining for intestinal MGAM was performed. Our results strongly suggest the
      presence and functioning of MGAM which disproved deficiency predictions based on
      SNP array analysis findings, classifying the deletion as a functional
      polymorphism. This study highlights a current clinical limitation of SNP arrays,
      i.e., distinguishing deleterious genomic alterations from misleading functional
      polymorphisms. We conclude that novel findings from SNP arrays should be
      clinically validated and published.

PMID- 23137570
TI  - Dietary treatment in phenylketonuria does not lead to increased risk of obesity
      or metabolic syndrome.
AB  - BACKGROUND: Little is known about the consequences of the special energy enriched
      diet used to treat patients with phenylketonuria (PKU) in terms of obesity and
      metabolic syndrome (MetSyn) development. OBJECTIVE: To investigate the prevalence
      of overweight and obesity, and its consequences in terms of body composition and
      MetSyn in early treated patients with PKU compared to controls. DESIGN: A sample
      of 89 patients with PKU (3-30 y; 14.4+/-6.6 y) and 79 controls (3-47 y; 16.3+/
      7.9 y) were studied. In the fasted state, anthropometric, body composition, blood
      pressure and analytical parameters [amino acids, glucose, insulin, total and HDL
      cholesterol (HDL-c), triglycerides (TG), high sensitivity c-reactive protein and
      uric acid] were performed. Data on dietary intake was collected. BMI was
      classified using WHO criteria, while the definition from International Diabetes
      Federation (IDF) was used for MetSyn. RESULTS: Prevalence of overweight and
      obesity (32.6% vs. 24.1%; p=0.293), body fat percentage (22% vs. 23.1%, p=0.581)
      and central obesity (36.9% vs. 36.4%, p=0.999) were comparable to controls.
      Patients revealed a higher TG/HDL-c (p<0.001). The prevalence of MetSyn was 1.5%
      and 6.1% in patients and controls, respectively. Patients and not controls with
      central obesity revealed a further significant increase in TG/HDL-c compared with
      those without central obesity (p=0.023). CONCLUSION: Patients and controls were
      similar in terms of overweight and obesity, body composition and MetSyn. However,
      the dyslipidemia in patients with PKU in relation to overweight and obesity may
      help us trying to understand the course and the etiology of MetSyn not only in
      PKU but also in the general population.

PMID- 23137571
TI  - MPV17: fatal hepatocerebral presentation in a Brazilian infant.

PMID- 23137572
TI  - Spotted fever group rickettsiae in ticks and fleas from the Democratic Republic
      of the Congo.
AB  - Little is known about the prevalence of spotted fever group (SFG) rickettsiae in
      ticks and fleas in the Democratic Republic of the Congo. In 2008, 12 Amblyomma
      compressum ticks were collected from 3 pangolins (Manis gigantea). Two
      Haemaphysalis punctaleachi ticks were collected from 2 African civets
      (Civettictis civetta congica), and one was collected from an antelope (Onotragus
      leche). A total of 111 Rhipicephalus sanguineus ticks, 23 Ctenocephalides canis
      fleas, 39 C. felis fleas, and 5 Trichodectes canis lice were sampled from 19
      dogs. One C. canis flea was collected from a human. Six of the 12 A. compressum
      ticks were positive for rickettsial DNA, as determined by genus-specific qPCR.
      The ompA gene sequences amplified from positive samples showed 100% homology with
      Rickettsia africae (GenBank accession number CP001612). The detection of Ri.
      africae in A. compressum ticks, which are highly specialized parasites of
      pangolins, is consistent with our previous data showing the presence of Ri.
      africae in A. compressum ticks from Liberia. No other ticks contained rickettsial
      DNA. A total of 9 C. canis fleas (39%, 9/23) and 37 C. felis fleas (95%, 37/39)
      that was collected from dogs and one C. canis flea collected from a human
      harbored Ri. felis.

PMID- 23137573
TI  - [Clinical practice guidelines in gastroenterology and hepatology. A resource
      underused by the Spanish Association for the Study of the Liver and the Spanish
      Association of Gastroenterology].

PMID- 23137574
TI  - [Endoscopic treatment of obesity].
AB  - Obesity is highly prevalent in many developed and developing countries and is on
      the increase. The range of obese patients suitable for endoscopic treatment may
      be very broad. The most widely applied treatment in Spain and elsewhere in Europe
      is the Allergan intragastric balloon. The effectiveness of this technique is good
      in the short-term but suboptimal in the long term and its safety profile is high.
      However, severe complications may occur and consequently the indication and
      implantation of this technique should not be trivialized. In addition, there are
      distinct endoscopic devices that help patients lose weight, through distinct
      mechanisms of action, but these devices are currently under technological
      development and awaiting scientific validation. It is too soon to recommend these
      techniques and they should only be evaluated in the context of clinical trials.

PMID- 23137575
TI  - Communicating the risk of side effects to rheumatic patients.
AB  - When proposing a new therapy, rheumatologists must inform patients of a range of
      therapeutic options and support them towards making an informed decision. This
      article introduces definitions of equipoise and a good decision, contrasts
      persuasion from informed patient choice, and discussed the effects of patient
      characteristics including cognition on decision making. It also describes and
      offers examples of techniques and visual formats utilized in patient decision
      aids to present risk estimates to reduce cognitive bias and maximize patient
      comprehension.

PMID- 23137576
TI  - Safety of urate-lowering therapies: managing the risks to gain the benefits.
AB  - Gout is a metabolic disorder of purine metabolism and uric acid elimination. Over
      time, acute gout can develop into a chronic, disabling arthropathy, often
      associated with multiple comorbidities. Gout patients have often been
      undertreated, partly because of the clinician's perceived risks of a therapy
      outweighing its potential benefits. The approval of new therapies to treat
      hyperuricemia in gout has led to a new understanding of gout management and
      medication safety regarding new and old therapies. This review focuses on
      potential safety issues of currently available urate-lowering therapies and
      outlines strategies to minimize risks so their benefits can be reached.

PMID- 23137577
TI  - Safety of bisphosphonates.
AB  - Bisphosphonates are antiresorptive medications widely prescribed for treating
      osteoporosis. In placebo-controlled clinical trials they have been shown to
      significantly reduce the risk of osteoporotic fractures. However, reports of
      atypical femoral fractures and osteonecrosis of the jaw have emerged with long
      term use, raising questions regarding their long-term safety. Additionally,
      questions have also emerged regarding the association between bisphosphonates and
      other rare adverse events, such as esophageal cancer and atrial fibrillation.
      This article summarizes the current knowledge regarding the major side effects
      associated with the use of bisphosphonates, identifies at-risk populations for
      these side effects, and provides guidance for their use.

PMID- 23137578
TI  - Nonserious infections: should there be cause for serious concerns?
AB  - Nonserious infections (NSIE) as colds, flu syndromes, and urinary tract
      infection, are the most common infections seen in patients with immune mediated
      inflammatory diseases. Yet, little is known about the impact of
      immunosuppression, particularly with tumor necrosis factor inhibitors (TNFi), on
      these infections. A systemic review of large, randomized controlled trials was
      conducted to identify incidence, types, and outcomes of NSIE associated with the
      most commonly prescribed TNFi: adalimumab, etanercept, and infliximab.

PMID- 23137579
TI  - Infections and biologic therapy in rheumatoid arthritis: our changing
      understanding of risk and prevention.
AB  - Patients with rheumatoid arthritis are at higher risk for serious infections and
      death from infection than the general public. Prednisone and biologic agents
      increase this risk, although the risk associated with biologics can be mitigated
      when such agents act as prednisone-sparing therapies. Some of the important
      causes of infectious morbidity in this setting are preventable with screening
      (eg, tuberculosis) or vaccination (eg, herpes zoster).

PMID- 23137580
TI  - Perioperative drug safety in patients with rheumatoid arthritis.
AB  - The expansion of therapeutic options for rheumatoid arthritis (RA) has improved
      the functional, quality of life, and radiographic outcomes for patients, although
      immunomodulatory and immunosuppressive effects may increase the potential for
      complications related to infection risk or wound healing after orthopedic
      surgery. Additionally, medications without significant effects on the immune
      system, such as nonsteroidal anti-inflammatory drugs, may have consequences in
      terms of bleeding or cardiovascular disease. Increased vigilance is required when
      using these medications, particularly in the perioperative period. This article
      considers the recent literature and data on the perioperative use of medications
      commonly used in RA.

PMID- 23137581
TI  - Malignancy risks with biologic therapies.
AB  - The management of rheumatoid arthritis (RA) dramatically changed in 1998 with the
      introduction of etanercept and infliximab for the treatment of RA and Crohn
      colitis. Nine biologic agents are currently in use for treating RA. However,
      speculation has grown that the long-term use of these biopharmaceuticals may
      alter normal immunosurveillance, thereby contributing to an individual's cancer
      risk. Whether malignancy is a consequence of rheumatoid inflammation or the
      therapies used to treat RA has been unclear until recently. This article
      addresses the growing data on the short- and long-term cancer risks associated
      with biologic use in RA.

PMID- 23137582
TI  - Safe use of antirheumatic agents in patients with comorbidities.
AB  - The burden of comorbid diseases is high among patients with rheumatoid arthritis
      (RA). These are often systemic manifestations of RA but may be chronic conditions
      that predate or develop post-RA diagnosis. Increased mortality in RA is
      predominantly from nonarticular causes. The expanded armamentarium of disease
      modifying drugs and biologics available has revolutionized management of
      articular disease but has made safe treatment of RA more complex. Drug-induced
      organ injury and side effects need to be kept in mind when initiating or
      modifying therapy.

PMID- 23137584
TI  - Rheumatic Disease Clinics of North America. Drug safety: managing innovation in
      rheumatology. Foreword.

PMID- 23137583
TI  - Comparative safety of therapies in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is the prototypic autoimmune disease with
      diverse clinical manifestations, affecting virtually all organ systems. A wide
      variety of medications are used for treatment, depending on organ involvement and
      severity. This article summarizes the adverse effects associated with different
      drugs currently used to treat SLE.

PMID- 23137585
TI  - Refining drug safety in rheumatology.
AB  - This issue explores several important safety concerns that currently plague the
      rheumatologist and health care providers who care for patients with rheumatic
      diseases. Weighing safety against efficacy can be a complex task that is best
      alleviated by understanding the issues, nature, and breadth of problems
      associated with drug use. Therapeutic decision-making must be evidence-based,
      judicious, and appropriate for the patient and situation. Understanding drug
      safety is paramount to ensuring both success of therapy and benefit to the
      patient. Similarly, it is important not to underestimate the impact of
      uncontrolled disease activity in decision-making. Drug safety must be weighed
      against the severity and risks of the disease under treatment. Clearly the
      benefit/risk ratio has improved for many of the therapies discussed in this book.
      The use of both conventional and novel therapies mandates an understanding of the
      mechanisms of action, unique toxicities, screening and monitoring measures, and
      rules for drug avoidance.

PMID- 23137586
TI  - Incongruence between the sexes in preferences for body and dorsal fin size in
      Xiphophorus variatus.
AB  - Female preference for male fin enhancements in poeciliid fishes may be driven by
      a preexisting perceptual bias for increased male lateral projection area (LPA).
      This hypothesis suggests that a male with enlarged body and/or fin size projects
      a larger image onto the female's retina at a given viewing distance, eliciting a
      greater sensory and thus behavioral response out of the female than a smaller
      male. Given the shared sensory/neural systems of opposite sex conspecifics, we
      might expect the LPA bias to also be present in males of at least some poeciliid
      species. However, we need not expect congruence between the sexes in the state of
      the bias over evolutionary time. To examine whether the sexes share a bias for
      sailfin-like dorsal fins, a trait not present in their evolutionary history, the
      bias favoring increased dorsal fin size and LPA observed in female Xiphophorus
      variatus, among other poeciliids, was investigated by testing male preference for
      dummy females varying in dorsal fin size, body size, and dorsal fin:body size
      ratio. In three sets of simultaneous choice experiments, males preferred females
      of larger body size when fin size was held constant and when total LPA was held
      constant, but showed no preference for larger fins when body size was held
      constant. The LPA bias is therefore less permissive in males than females with
      selection favoring a male's ability to discriminate between female body size - an
      indicator of fertility/fecundity - and fin size, which offers no known fitness
      benefits.

PMID- 23137587
TI  - Validating methods for estimating endocranial volume in individual red deer
      (Cervus elaphus).
AB  - Comparing brain sizes is a key method in comparative cognition and evolution.
      Brain sizes are commonly validated by interspecific comparisons involving animals
      of varying size, which does not provide a realistic index of their accuracy for
      intraspecific comparisons. Intraspecific validation of methods for measuring
      brain size should include animals of the same age and sex to ensure that
      individual differences can be detected in animals of similar size. In this study
      we compare three methods of measuring the endocranial volume of 33 red deer
      skulls to investigate the accuracy of each method. Methods for estimating
      endocranial volume included scanning each skull using computerised tomography
      (CT) and quantifying the volume with OsiriX software, filling the cranium with
      glass beads and measuring the bead volume, and linear measurements (length,
      width, and height) of the cranium using callipers. CT scan volumes were highly
      correlated with results from the bead method, but only moderately correlated with
      the linear method. This study illustrates the importance of validating
      intraspecies measurement methods, which allows for the accurate interpretation of
      results.

PMID- 23137588
TI  - Nausea and vomiting in advanced cancer: the Cleveland Clinic protocol.
AB  - Nausea and vomiting are common and distressing symptoms in advanced cancer. Both
      are multifactorial and cause significant morbidity, nutritional failure, and
      reduced quality of life. Assessment includes a detailed history, physical
      examination and investigations for reversible causes. Assessment and management
      will be influenced by performance status, prognosis, and goals of care. Several
      drug classes are effective with some having the added benefit of multiple routes
      of administration. It is our institution's practice to recommend metoclopramide
      as the first drug with haloperidol as an alternative antiemetic. Dexamethasone
      should be used for patients with central nervous system metastases or bowel
      obstruction. If your patient is near death, empiric metoclopramide, haloperidol
      or chlorpromazine is used without further investigation. For patients with a
      better prognosis, we exclude reversible causes and use the same first-line
      antiemetics, metoclopramide and haloperidol. For those who do not respond to
      first-line single antiemetics, olanzapine is second line and ondansetron is
      third. Rarely do we use combination therapy or cannabinoids. Olanzapine as a
      single agent has a distinct advantage over antiemetic combinations. It improves
      compliance, reduces drug interactions and has several routes of administration.
      Antiemetics, anticholinergics, octreotide and dexamethasone are used in
      combination to treat bowel obstruction. In opiod-na'ive patients, we prefer
      haloperidol, glycopyrrolate and an opioid as the first-line treatment and add or
      substitute octreotide and dexamethasone in those who do not respond. Non
      pharmacologic interventions (mechanical stents and percutaneous endoscopic
      gastrostomy tubes) are used when nausea is refractory to medical management or
      for home-going management to relieve symptoms, reduce drug costs and
      rehospitalization.

PMID- 23137589
TI  - Cardiac magnetic resonance imaging in a premature baby with interrupted aortic
      arch and aortopulmonary window.
AB  - Aortopulmonary window is a communication between the main pulmonary artery and
      the ascending aorta in the presence of two separate semilunar valves. The
      combination of an aortopulmonary window with interrupted aortic arch is rare. We
      discuss the unique case of an extremely premature infant weighing 1.7 kilograms
      who underwent cardiovascular magnetic resonance imaging as a pre-operative
      assessment in a high-field open 1.0 Tesla magnetic resonance imaging system as a
      one-stop investigation before complete repair.

PMID- 23137590
TI  - [Reply].

PMID- 23137591
TI  - [Clinical characteristics and treatment of patients attending an Emergency
      Department due to decompensation of chronic obstructive pulmonary disease].

PMID- 23137592
TI  - [Giant tumour as a late presenting manifestation of vascularized calcified
      myonecrosis after gunshot injury].

PMID- 23137593
TI  - PI3Ks and small GTPases in neutrophil migration: two sides of the same coin.
AB  - Cell migration is a key event in physiological processes such as embryonic
      development, tissue repair, angiogenesis and immune responses. Alteration of the
      migration program is an important component in multiple pathologies, including
      chronic inflammation, autoimmunity and tumor metastasis. Understanding of the
      precise mechanisms at the basis of cellular migration may lead to the
      identification of novel therapeutic approach for these diseases. Recent evidences
      show that the interplay between the lipid kinases phosphatidylinositol 3-kinase
      (PI3Ks) and small GTPases play a critical role in driving cell migration. In this
      review we will describe the role of these molecules and the interaction between
      their signal cascades in leukocyte polarization and amoeboid migration.

PMID- 23137594
TI  - Exploring genome-wide datasets of MHC class II antigen presentation.
AB  - MHC class II molecules (MHCII) are critical for presenting antigens to CD4(+) T
      cells. They control ignition of CD4(+) T cells and are as such involved in most
      auto-immune diseases. To define proteins and pathways controlling MHCII antigen
      presentation and expression, we performed a genome-wide flow cytometry based RNAi
      screen. Hits were subsequently classified by two screens that monitored the
      intracellular distribution and transcription of MHCII. This multi-dimensional
      approach allowed subclassification of hits into functional groups as a first step
      to defining new pathways controlling MHCII antigen presentation. The datasets
      from this screen are used as a template for several follow-up studies. This
      overview focuses on how data from genome-wide screens can be used for target-lead
      finding, data mining, systems biology and systematic cell biology.

PMID- 23137595
TI  - Medially posted insoles consistently influence foot pronation in runners with and
      without anterior knee pain.
AB  - Anterior knee pain (AKP) is a common injury among runners and effectively treated
      with posted insoles and foot orthotics. While clinically effective, the
      underlying biomechanical mechanisms that bring about these improvements remain
      debatable. Several methodological factors contribute to the inconsistent
      biomechanical findings, including errors associated with removing and reattaching
      markers, inferring foot motion from markers placed externally on a shoe, and
      redefining segmental coordinate systems between conditions. Therefore, the
      purpose of this study was to evaluate the influence of medially posted insoles on
      lower extremity kinematics in runners with and without AKP while trying to limit
      the influence of these methodological factors. Kinematics of 16 asymptomatic and
      17 runners with AKP were collected while running with and without insoles.
      Reflective markers were attached to the surface of the calcaneus and kept in
      place (as opposed to detached) between conditions, eliminating the error
      associated with reattaching markers and redefining segmental coordinate systems.
      Using these methods, no significant interactions between insole and injury and
      the main effect of injury were detected (p>0.05); therefore, means were pooled
      across injury. Insoles, on average, reduced peak eversion by 3.6 degrees  (95%
      confidence interval -2.9 degrees  to -4.3 degrees ), peak eversion velocity by
      53.2 degrees /s (95% confidence interval -32.9 to -73.4) and eversion range of
      motion by 1.33 (95% confidence interval -0.8 to -1.9). However, while insoles
      systematically reduced eversion variables, they had small influences on the
      transverse plane kinematics of the tibia or knee, indicating that they may bring
      about their clinical effect by influencing other variables.

PMID- 23137596
TI  - Nursing education trends: future implications and predictions.
AB  - This article examines current trends in nursing education and proposes numerous
      transformations needed to ensure that programs are relevant, fully engage
      learners, reflect evidence-based teaching practices, and are innovative. Such
      program characteristics are essential if we are to graduate nurses who can
      practice effectively in today's complex, ambiguous, ever-changing health care
      environments and who are prepared to practice in and, indeed, shape tomorrow's
      unknown practice environments.

PMID- 23137597
TI  - A report on a national study of doctoral nursing faculty.
AB  - This article reports on a national study of doctoral nursing faculty, including
      both PhD and Doctor of Nursing Practice (DNP) faculty. Using a national sample of
      624 doctoral nursing faculty, we surveyed individuals on a variety of issues,
      including succession planning, retirement, quality of life as a doctoral faculty
      member, their views on the new DNP degree, and how they view the future of
      doctoral nursing education. Study implications for both DNP and PhD faculty are
      explored and the meaning of the findings of the study for the future are
      discussed, including new items that will be investigated in a repeat survey in
      2012.

PMID- 23137598
TI  - The paradigm shift.
AB  - This article examines current trends in nursing education and proposes
      undergraduate curriculum changes that are needed to meet the needs and goals of
      the Institute of Medicine Report: The Future of Nursing, Leading Change,
      Advancing Health, and The Patient Protection and Affordable Care Act. Curricular
      changes were developed and implemented during the development of the Affordable
      Care Act, the Future of Nursing Initiative report, and the Carnegie Report on
      Undergraduate Nursing Education. The changes will continue to evolve dynamically
      and are presented here for consideration.

PMID- 23137599
TI  - Primary care nurse practitioner clinical education: challenges and opportunities.
AB  - The Institute of Medicine report and the passage of the Patient Protection and
      Affordable Care Act present significant opportunities for the nursing profession.
      As the largest group of primary care providers, nurse practitioners are the
      critical element in the provision of comprehensive primary care, and a critical
      element to the success of the redesigned health care system. Nurse practitioners
      can bridge the gap between coverage and access and provide the patient-centered
      innovative approaches needed. There are, however, significant barriers that need
      to be addressed. This article presents a framework for creating innovative
      approaches to the redesign of nurse practitioner clinical education.

PMID- 23137600
TI  - Testing computer-based simulation to enhance clinical judgment skills in senior
      nursing students.
AB  - Expert clinical judgment is the culmination of knowledge and experiential
      learning that includes reflections on immediate problems and past experience. In
      nursing education, experiential learning is augmented through the use of
      simulated clinical experiences provided in simulation laboratories. Various
      simulations have been reported; however, few studies target the effectiveness of
      experiential learning using a computer-based simulation available to the
      individual user. An educational intervention based on Kolb's Experiential
      Learning Theory (ELT) is examined in this pilot study, to determine the
      feasibility of conducting a future larger-scale research project on the
      effectiveness of ELT in enhancing development of clinical judgment skills.

PMID- 23137601
TI  - Transdisciplinary simulation: learning and practicing together.
AB  - The Institute of Medicine, partnering with national private foundations, has
      challenged existing approaches to health care delivery and patient safety by
      suggesting a sweeping redesign of the entire U.S. health care system. This
      article explores the historical and philosophic imperative to change health care
      education to a seamless transdisciplinary model to foster interprofessional
      communication and collaboration during the formative training years. To improve
      patient safety and quality of care and reduce medical error, students in health
      care disciplines will need to be educated together to practice together
      effectively.

PMID- 23137602
TI  - Learning from business: incorporating the Toyota Production System into nursing
      curricula.
AB  - The faculty at Drexel University decided to investigate a new model to transform
      nursing education, aiming to produce a new skill set that would serve to improve
      the transition of nursing graduates from academic settings to practice, to better
      serve the needs of patients and reduce medical error. Faculty looked to the
      Toyota Production System (TPS), which has established credibility in industry and
      health care settings. TPS has demonstrated increased efficiency and
      effectiveness, reduced cost, and enhanced achievement of stated goals. Drexel
      University is the first academic institution to incorporate the principles of the
      TPS into nursing education.

PMID- 23137603
TI  - Preparing nurses to care for people with developmental disabilities: perspectives
      on integrating developmental disabilities concepts and experiences into nursing
      education.
AB  - The argument that nursing curricula have not adequately prepared graduates to
      provide appropriate care for individuals with intellectual disabilities and
      developmental disabilities (DDs) has been put forward for a decade or more. This
      is of concern because the number of individuals with DDs has been increasing at a
      rapid rate. Undergraduate and graduate nursing curricula should address concepts
      of care for DDs across the lifespan and develop strategies to provide students
      with clinically relevant experiences to support development of competencies for
      care of this population. Exemplar strategies from the literature are described
      along with recommendations for further work.

PMID- 23137604
TI  - Genomic literacy and competent practice: call for research on genetics in nursing
      education.
AB  - This article presents an argument for research on the practical outcomes of
      genetics education in professional nursing programs. Nurse educators should
      aggressively conduct educational outcomes research on the translation of genetics
      core competencies at all levels of clinical practice. There should be a
      systematic examination of the factors, that influence graduate nurses'
      applications of concepts to patient care including type of educational
      preparation in genetics. The best way to improve health is to understand normal
      genome biology and its relationship to disease biology. Assuring genetics and
      genomic literacy among all nurses is a crucial task for contemporary nursing
      education programs.

PMID- 23137605
TI  - The doctor of nursing practice graduate as faculty member.
AB  - This article focuses on the emerging role of the Doctor of Nursing Practice (DNP)
      graduate as faculty member. Discussion includes historical composition of
      faculties. Re-evaluation of Boyer's model of scholarship in relation to faculty
      roles is examined. Discussion includes barriers facing current DNP faculty as
      well as the potential advantages that DNP graduates may make toward school of
      nursing faculties. Discussion concludes with considerations for the future of the
      discipline as demographics and traditional values shift over time.

PMID- 23137606
TI  - Promoting a healthy workplace for nursing faculty and staff.
AB  - Promoting a healthy workplace in academic nursing settings is vital to recruit
      new faculty and enhance the work life of all faculty and staff for retention and
      happiness. When a healthy work environment is fostered, incivility becomes
      unacceptable, and individuals embrace a culture where all can flourish. This
      article addresses the imperative of a healthy workplace, with practical
      suggestions for making the academic setting in schools of nursing one of optimism
      and confidence where future generations of nurse leaders are developed.

PMID- 23137607
TI  - The experience of a new deanship for two Robert Wood Johnson Foundation executive
      nurse fellows.
AB  - With the graying of the professoriate, many deans in nursing are moving toward
      retirement, which provides an opportunity for emerging leaders to move into
      deanships. New deans move through predictable stages and enjoy a honeymoon,
      allowing for some mistakes that might not be tolerated later. Early wins are
      essential in addition to planned changes so as not to overwhelm faculty with
      change. It is critical to learn the new culture, identify leaders, perform a
      thorough assessment as the basis for a strategic plan, and be honest and
      transparent. The ability to mobilize a cohesive, functioning team is critical to
      success.

PMID- 23137608
TI  - New developments in nursing education: a focus on contemporary content,
      pedagogies, deans, and trends.

PMID- 23137609
TI  - Does developmental exposure to perflurooctanoic acid (PFOA) induce
      immunopathologies commonly observed in neurodevelopmental disorders?
AB  - Immune comorbidities often are reported in subsets of patients with
      neurodevelopmental disorders, including autism spectrum disorders and attention
      deficit hyperactivity disorder. A common immunopathology is an increase in serum
      autoantibodies against myelin basic protein (MBP) relative to control patients.
      Increases in autoantibodies suggest possible deficits in self-tolerance that may
      contribute to the formation of brain-specific autoantibodies and subsequent
      effects on the central nervous system (CNS). Oppositely, the formation of
      neuronal autoantibodies may be a reaction to neuronal injury or damage.
      Perfluorooctanoic acid (PFOA) is an environmental pollutant that induces
      multisystem toxicity in rodent models, including immunotoxicity and
      neurotoxicity. We hypothesized that developmental exposure to PFOA may induce
      immunotoxicity similar to that observed in subsets of patients with
      neurodevelopmental disorders. To test this hypothesis, we evaluated subsets of T
      cells from spleens, serum markers of autoreactivity, and levels of MBP and T cell
      infiltration in the cerebella of adult offspring exposed to 0.02, 0.2, or 2mg/kg
      of PFOA given to dams from gestation through lactation. Litter weights of
      offspring from dams exposed to 2mg/kg of PFOA were reduced by 32.6%, on average,
      from postnatal day one (PND1) through weaning (PND21). The percentage of splenic
      CD4+CD25+Foxp3+ T cells in male and female offspring from dams exposed to 2mg/kg
      of PFOA was reduced by 22% relative to the control percentage. Ex vivo co
      cultures of splenic CD4+CD25+ T cells and CD4+CD25- T cells from dosed male
      offspring produced less IL-10 relative to control cells. Anti-ssDNA, a serum
      marker of autoreactivity, was decreased by 26%, on average, in female offspring
      from dams exposed to 0.02 and 2mg/kg PFOA. No other endpoints were statistically
      different by dose. These data suggest that developmental PFOA exposure may impact
      T cell responses and may be a possible route to downstream effects on other
      systems.

PMID- 23137610
TI  - External anterior abdominal wall and pelvic hernias with emphasis on the key
      diagnostic features on MDCT.
AB  - Clinical diagnosis of abdominal wall hernias can be challenging. These common
      entities can be symptomatic and prone to complications. Pre-surgical planning and
      investigation of acute presentations can be achieved by multidetector computed
      tomography (MDCT) with its added multiplanar reformatting capability. Here we
      delineate the important anatomical landmarks and key signs on CT of a wide
      spectrum of external anterior abdominal wall and pelvic hernias.

PMID- 23137611
TI  - Treatment of cuff-related tracheal stenosis with a fully covered retrievable
      expandable metallic stent.
AB  - AIM: To investigate the clinical effectiveness, complications, and optimal
      duration of use of covered retrievable expandable metallic stents in the
      management of cuff-related tracheal stenosis. MATERIALS AND METHODS: Twenty-one
      patients with cuff-related tracheal stenosis, Meyer-Cotton grade II (29%) and III
      (71%), who underwent fluoroscopically guided placement of covered retrievable
      expandable metallic stents were studied. Sixty-four-section computed tomography
      (CT) and bronchovideoscopy were performed prior to stent insertion, 1 month after
      stent insertion, in the case of stent-related complications, and after stent
      removal. Clinical manifestations, Hugh-Jones classification, and forced
      expiratory volume in 1 s (FEV1) were used to evaluate respiratory function before
      and after stent insertion and removal. The diameter of the stricture and FEV1
      changes before insertion and after removal were analysed using the paired samples
      t-test. A p-value of <=0.05 was considered statistically significant. RESULTS:
      Twenty-one patients had 27 covered retrievable expandable metallic stents placed.
      Stents were electively removed from 20 patients. The median duration of stent
      placement was 5 months (range 4-12 months). One stent was not removed due to
      mucopolysaccharidosis type II (MPS II or Hunter syndrome) with tracheomalacia.
      After stent removal, airway dimensions increased and airway occlusion was
      symptomatically relieved in all patients. CT and bronchovideoscopy showed patent
      lumens with increased dimensions. Stent-related complications occurred in 19
      (91%) patients, including granulation tissue formation (n = 18, 86%), stent
      migration and stent expectoration (n = 2, 10%), mucus plugging (n = 1, 5%), and
      halitosis (n = 6, 29%). Some patients experienced multiple complications, which
      were all managed effectively while the stent was still in place. There was a
      statistically significant difference in the diameter of the stricture and FEV1
      between the time of stent insertion and removal. An improvement in Hugh-Jones
      classification of greater than one grade was seen in patients after stent
      removal. CONCLUSION: Temporary placement of a fully covered retrievable
      expandable metallic stent is safe and effective in cuff-related tracheal
      stenosis. The optimal duration of stent placement may be 4-8 months.

PMID- 23137612
TI  - The gustatory sensilla on the endophytic ovipositor of Odonata.
AB  - The present paper aims at describing the fine structure of coeloconic sensilla
      located on the cutting valves of the endophytic ovipositor of two Odonata
      species, the anisopteran Aeshna cyanea (Aeshnidae) and the zygopteran Ischnura
      elegans (Coenagrionidae), by carrying out parallel investigations under SEM and
      TEM. In both species these coeloconic sensilla are innervated by four unbranched
      neurons forming four outer dendritic segments enveloped by the dendrite sheath.
      One dendrite terminates at the base of the peg forming a well developed tubular
      body, while the other three enter the peg after interruption of the dendrite
      sheath. The cuticle of the peg shows an apical pore and a joint membrane. This
      last feature, together with the tubular body and the suspension fibers, represent
      the mechanosensory components of the sensillum while the pore and the dendrites
      entering the peg allow chemoreception. The ultrastructural organization of these
      coeloconic sensilla is in agreement with the one reported for insect gustatory
      sensilla. Our investigation describes for the first time typical insect gustatory
      sensilla in Odonata. Electrophysiological and behavioral studies are needed to
      verify the role that these structures can perform in sensing the egg-laying
      substrata.

PMID- 23137613
TI  - Autoimmune rheumatic disease associated symptoms in fibromyalgia patients and
      their influence on anxiety, depression and somatisation: a comparative study.
AB  - OBJECTIVES: In this study we evaluated the frequency of autoimmune rheumatic
      disease associated major symptoms in fibromyalgia (FM) patients, and the
      association between their presence and anxiety, depression and somatisation.
      METHODS: Two hundred and thirty-two FM, 78 systemic lupus erythematosus (SLE)
      patients and 70 healthy controls were included. All subjects were questioned face
      to-face for the presence of autoimmune rheumatic disease-associated symptoms and
      antinuclear antibody (ANA) was determined. All FM patients were questioned for
      the severity of pain and symptoms of FM by using a visual analogue scale. In
      addition, all subjects were interrogated for anxiety, depression, somatic
      symptoms and neuropathic pain by using different validated questionnaires.
      RESULTS: FM patients had significantly higher frequency of photosensitivity
      (27.6% vs. 11.4%) and Raynaud phenomenon (22% vs. 10%) when compared to controls
      (p-values, 0.005 and 0.026). FM patients had significantly lower frequencies of
      photosensitivity, oral ulcers, xerostomia, and xerophthalmia than SLE patients
      (all p-values <0.001). ANA positivity was 11.8% in FM patients and 7.1% in
      healthy controls. ANA-positive and negative FM patients had similar frequencies
      of autoimmune rheumatic disease symptoms. FM patients with photosensitivity had
      higher anxiety (p=0.002), somatic symptoms (p=0.015) and neuropathic pain
      (p=0.03) scores than others. FM patients with Raynaud had higher anxiety
      (p=0.004), depression (p=0.001), somatic symptom (p<0.001) and neuropathic pain
      scores than others. CONCLUSIONS: The presence of which findings in FM seems to be
      associated with anxiety, depression, and somatization rather than ANA positivity
      and disease severity.

PMID- 23137614
TI  - Reviewing the evidence on nodding syndrome, a mysterious tropical disorder.
AB  - OBJECTIVES: To review the literature on the prevalence, clinical manifestations,
      pathogenesis, treatment, and implications of nodding syndrome (NS). METHODS: This
      is a narrative review. RESULTS: NS is a mysterious tropical disorder that is
      emerging in South Sudan, southern Tanzania, and northern Uganda. Over the past
      decade, thousands of children have become affected, but the prevalence is
      unknown. NS is characterized by an occasional nodding of the head, which is
      considered as a form of epilepsy. After symptoms appear, the patient's health
      rapidly deteriorates. Seizures, stunted growth, and mental retardation may
      appear. In endemic areas, NS is increasingly becoming a public health problem
      with high morbidity and mortality, and severe social, psychological, and economic
      implications. However, the pathogenesis is unknown. Evidence suggests a role for
      Onchocerca volvulus, the parasitic filarial worm responsible for river blindness,
      which is highly endemic in these areas. There is no cure for NS, and treatment is
      symptomatic with common anticonvulsants to improve the quality of life.
      CONCLUSIONS: NS seems to be a rapidly growing problem in several eastern African
      countries. Although it is starting to receive more and more attention in the
      scientific literature, little is known about NS. A better understanding of the
      pathogenesis may lead to prevention and treatment opportunities.

PMID- 23137615
TI  - Noise-enhanced clustering and competitive learning algorithms.
AB  - Noise can provably speed up convergence in many centroid-based clustering
      algorithms. This includes the popular k-means clustering algorithm. The
      clustering noise benefit follows from the general noise benefit for the
      expectation-maximization algorithm because many clustering algorithms are special
      cases of the expectation-maximization algorithm. Simulations show that noise also
      speeds up convergence in stochastic unsupervised competitive learning, supervised
      competitive learning, and differential competitive learning.

PMID- 23137616
TI  - Vaginal cells of smokers are more resistant to human papillomavirus infection
      than that of non-smokers.
AB  - To evaluate effect of HPV and smoking on DNA double-strand breaks in vaginal
      samples, vaginal specimens collected from participants (n=76) were classified
      based on HPV and smoking status, and DNA double-strand breaks measured using
      comet assay. Mean tail length (31.2+/-18.7MUm) and tail moment (2.4+/-2.8
      arbitrary units) for HPV-positive patients were lower (p<0.001) compared with HPV
      negative patients (61.7+/-22.6MUm; 8.7+/-4.9AU). Never-smokers were found to have
      a higher level (p<0.001) of double-strand breaks (57.7+/-24.5MUm, 7.5+/-5.5AU)
      compared with ever smokers (35.3+/-21.9MUm; 3.4+/-3.7AU). Among HPV infected
      patients, never-smokers have more double-strand breaks compared to smokers
      (p<0.001) which correlated with age (p<0.001). Highly differentiated vaginal
      epithelium may be resistant to DNA damage associated with HPV infection and
      smoking, which may be attributed to adoptive survival mechanisms of vaginal
      epithelium.

PMID- 23137617
TI  - Characterization of the elastic-plastic behavior of intermetallic coatings growth
      on medical stainless steel by instrumented ultramicroindentation.
AB  - The purpose of this work is to study the elastoplastic properties of novel
      intermetallic coatings grown by hot dipping on medical steel 316 LVM and their
      correlation with the scratch resistance by means of instrumented
      ultramicroindentation techniques. Elastoplastic properties are defined by the
      plasticity index (PI), which correlates the hardness and the Young's modulus, and
      the yield strength that delimits the elastic-plastic transition. To avoid
      overestimations of the PI due to the so-called indentation size effect,
      macroscopic hardness values were determined. The PI of the coating increases from
      0.6 to 0.8 with increasing immersion time. These values are always lower than
      those of the bare substrate (0.9) but higher than those found for ceramics
      (~0.5). The increase of the PI is accompanied by a decrease in the yield strength
      from 0.73 to 0.34 GPa, which highlights the relevance of the compressive residual
      stresses and their relaxation with increasing immersion time. The higher
      plasticity is shown by higher apparent friction coefficients (0.159), which are
      always lower than those of the bare steel (0.264). Therefore, these intermetallic
      coatings could be considered "hard but tough" coatings, suitable for enhancing
      the wear resistance of the medical steel, especially when using short periods of
      immersion. The study provides evidence that the load-depth curve of indentation
      contains abundant information and that its analysis can be used to determine
      various mechanical properties of coatings that could be important for load
      bearing components.

PMID- 23137618
TI  - Silicon nitride films for the protective functional coating: blood compatibility
      and biomechanical property study.
AB  - Behaviors of silicon nitride films and their relation to blood compatibility and
      biomechanical have been interesting subjects to researchers. A systematic blood
      compatibility and biomechanical property investigation on the deposition of
      silicon-nitride films under varying N2 and CF4 flows was carried out by direct
      current unbalanced magnetron sputtering techniques. Significant role of surface
      property, chemical bonding state of silicon nitride film and blood compatibility,
      mechanical properties for the films were observed. The chemical bonding
      configurations, surface topography, contact angle and mechanical properties were
      characterized by means of X-ray photoelectron spectroscopy (XPS), atomic force
      microscopy (AFM) and nano-indentation technique and CSEM pin-on-disk tribometer.
      Blood compatibility of the films was evaluated by platelet adhesion
      investigation. The results of the platelet adhesion tests shown that the effect
      of fluorine and nitrogen-doped revealed an intimate relationship between the
      ratio of polar component and dispersion component of the surface energy and its
      hemocompatibility. Si-N-O coating can be a great candidate for developing
      antithrombogenic surfaces in blood contacting materials. The chemical bonding
      state made an adjustment in microstructured surfaces, once in the totally
      wettable configuration, may improve the initial contact between platelet and
      biomedical materials, due to the appropriate ratio of dispersion component and
      polar component. To resist wear, biomedical components require coatings that are
      tough and hard, have low friction, and are bio-inert. The study suggests that by
      Si-N coating the metal surfaces could be a choice to prolong the life of the
      sliding pair Co-Cr-Mo alloy/UHMWPE implants.

PMID- 23137619
TI  - Laser deposition and deformation behavior of Ti-Nb-Zr-Ta alloys for orthopedic
      implants.
AB  - Microstructure and mechanical properties of laser deposited complex quaternary Ti
      34Nb-7Zr-7Ta (all wt%), an orthopedic load-bearing implant alloy, has been
      investigated in detail in both as-deposited as well as heat-treated (beta
      solutionized and quenched) conditions. The difference in stress-strain behavior
      of this alloy in the above conditions has been characterized using scanning
      electron microscopy (SEM), orientation imaging microscopy (OIMTM) and
      transmission electron microscopy (TEM). Compared to the sample in heat-treated
      condition, the as-deposited sample showed evidence of strong growth related
      texture. Again in the as-deposited post tensile-tested condition formation of a
      high density of shear bands, possibly arising from slip localization due to
      shearing of omega precipitates in the beta matrix is observed. TEM investigations
      also show the presence of lenticular shaped deformation induced omega phase
      within the shear bands. In contrast, in case of the beta-solutionized sample,
      twinning and the formation of stress-induced plates appears to be the primary
      mode of deformation. The change in deformation mechanism and thus the tensile
      property of this alloy could be attributed to the crystallographic texture along
      the growth direction as well as diffusion mediated isothermal omega precipitates,
      that cause an enrichment of Nb and Ta in the beta matrix, during the laser
      deposition process. This is no longer present after the solutionizing treatment.

PMID- 23137620
TI  - Nano-indentation on amorphous calcium phosphate splats: effect of droplet size on
      mechanical properties.
AB  - Droplet processing technologies and many biological processes use disk-like or
      hemispherical shapes for construction or the design of surfaces. The ability to
      tune the characteristics and properties of a surface is important at the micro-
      and nano-scale. The influence of size on the mechanical properties is presently
      unknown. This work set out to produce splats from different droplet sizes (20-40
      MUm, 40-60 MUm and 60-80 MUm), and then determine the deposit characteristics and
      mechanical properties. All splats produced by melting particles in a flame and
      depositing onto a polished titanium surface were amorphous, as determined by
      Raman micro-spectrometry. The topography shown in an optical and scanning
      electron microscope and topographically mapped using the scanning mode of the
      nano-indenter revealed a flattened hemispherical deposit. The critical nano
      indentation load for determining the true hardness decreased with increasing
      splat size; for 20-40 MUm, 40-60 MUm and 60-80 MUm splats the critical load was
      19, 16, 11 mN respectively compared to 30 mN for sintered hydroxyapatite. Higher
      loads are required to cause cracking and delamination in smaller splats. A load
      between 40 and 60 mN was required for delamination of the splat. Delamination of
      the splats could offer a new means to determine the adhesion of splats on low
      roughness surfaces.

PMID- 23137621
TI  - Experimental analysis and numerical modeling of mollusk shells as a three
      dimensional integrated volume.
AB  - In this paper, a new numerical technique is presented to accurately model the
      geometrical and mechanical features of mollusk shells as a three dimensional (3D)
      integrated volume. For this purpose, the Newton method is used to solve the
      nonlinear equations of shell surfaces. The points of intersection on the shell
      surface are identified and the extra interior parts are removed. Meshing process
      is accomplished with respect to the coordinate of each point of intersection. The
      final 3D generated mesh models perfectly describe the spatial configuration of
      the mollusk shells. Moreover, the computational model perfectly matches with the
      actual interior geometry of the shells as well as their exterior architecture.
      The direct generation technique is employed to generate a 3D finite element (FE)
      model in ANSYS 11. X-ray images are taken to show the close similarity of the
      interior geometry of the models and the actual samples. A scanning electron
      microscope (SEM) is used to provide information on the microstructure of the
      shells. In addition, a set of compression tests were performed on gastropod shell
      specimens to obtain their ultimate compressive strength. A close agreement
      between experimental data and the relevant numerical results is demonstrated.

PMID- 23137622
TI  - Property-process relations in simulated clinical abrasive adjusting of dental
      ceramics.
AB  - This paper reports on property-process correlations in simulated clinical
      abrasive adjusting of a wide range of dental restorative ceramics using a dental
      handpiece and diamond burs. The seven materials studied included four mica
      containing glass ceramics, a feldspathic porcelain, a glass-infiltrated alumina,
      and a yttria-stabilized tetragonal zirconia. The abrasive adjusting process was
      conducted under simulated clinical conditions using diamond burs and a clinical
      dental handpiece. An attempt was made to establish correlations between process
      characteristics in terms of removal rate, chipping damage, and surface finish and
      material mechanical properties of hardness, fracture toughness and Young's
      modulus. The results show that the removal rate is mainly a function of hardness,
      which decreases nonlinearly with hardness. No correlations were noted between the
      removal rates and the complex relations of hardness, Young's modulus and fracture
      toughness. Surface roughness was primarily a linear function of diamond grit size
      and was relatively independent of materials. Chipping damage in terms of the
      average chipping width decreased with fracture toughness except for glass
      infiltrated alumina. It also had higher linear correlations with critical strain
      energy release rates (R2=0.66) and brittleness (R2=0.62) and a lower linear
      correlation with indices of brittleness (R2=0.32). Implications of these results
      can provide guidance for the microstructural design of dental ceramics, optimize
      performance, and guide the proper selection of technical parameters in clinical
      abrasive adjusting conducted by dental practitioners.

PMID- 23137623
TI  - A story of Cu,Zn superoxide dismutase, peroxymonocarbonate, and pseudo-second
      order rate constants.

PMID- 23137624
TI  - Two hypotheses for the oxidation of SOD1-Cu(I).

PMID- 23137625
TI  - Successful treatment of incidental prostate cancer by radical transurethral
      resection of prostate cancer.
AB  - BACKGROUND: To evaluate the rationale for RTUR-PCa against pT1a/b cancer, we
      analyzed oncological and functional outcomes. PATIENTS AND METHODS: Fifty-six
      patients with incidental prostate cancer were included and the age ranged from 66
      to 91 years (mean, 76.6; median, 75.0). Preoperative prostate specific antigen
      (PSA) levels were between 0.70 and 44.1 ng/mL (mean, 5.90; median, 4.60). We
      performed 69 RTUR-PCa's by resecting and fulgurating the residual prostate
      tissues after previous transurethral resection of the prostate. Prostate specific
      antigen nonrecurrence rate was calculated by Kaplan-Meier method. RESULTS: Follow
      up duration of 51 patients was mean +/- SD 64.1 +/- 21.6 months (median, 67.8
      months; range, 13.8-99.8) excluding 5 patients that were lost to follow-up.
      Prostate specific antigen failure developed in 3 patients (5.9%). In the other 48
      patients, PSA stabilized as follows: PSA <= 0.01, 24 cases; <= 0.02, 5 cases; <=
      0.03, 6 cases; <= 0.04, 3 cases; <= 0.1, 7 cases; and <= 0.4, 3 cases. Prostate
      specific antigen nonrecurrence rates were 100% for pT2a and 91.3% for pT2b at the
      mean follow-up period of 64.1 months. Nonrecurrence rate grouped by D'Amico
      classification system were 100% in the low-risk group, 94.7% in the intermediate
      risk group, and 88.2% in the high-risk group, respectively. Water intoxication
      did not develop and no patients required transfusion. Bladder neck contracture,
      which developed in 22 out of 51 patients (43.1%), was the most frequent
      postoperative complication. Postoperative incontinence was temporary and
      disappeared within 3 months in all patients. CONCLUSION: Satisfactory oncologic
      and functional results suggest that RTUR-PCa could be a promising option for
      radical treatment against incidental prostate cancer.

PMID- 23137626
TI  - Detection of microalbuminuria: a simple test for prognosis in severe burns.
AB  - PURPOSE: To evaluate the effectiveness of microalbuminuria monitoring in the
      management of patients with severe burns. METHODS: Consecutive patients admitted
      to the burn unit with total body surface area burn between 20% and 50% were
      examined for microalbuminuria during the hospitalisation. The findings were
      correlated to different clinical variables usually encountered in this patient
      category. RESULTS: Microalbuminuria was found in patients with inhalation
      injuries (100%), systemic inflammatory response syndrome (SIRS, 88.4%), burn
      sepsis (95.1%) and postoperatively (94.9%). CONCLUSION: Microalbuminuria is the
      only simple, non-invasive, bedside, immediate and cost-effective test to indicate
      for occurrence of SIRS, if the other variables were stabilised. It can be
      measured with every urine void or more often when a urinary catheter is inserted.
      This will affect our management of patients with severe burns.

PMID- 23137627
TI  - nNOS expression in the brain of rats after burn and the effect of the ACE
      inhibitor captopril.
AB  - OBJECTIVE: To investigate the role of endogenous neuronal nitric oxide synthase
      (nNOS) on brain injury after burn and the effects of the captopril. METHODS:
      Wistar albino rats (200-250 g) were exposed on the dorsal surface to 90 degrees C
      (burn) or 25 degrees C (sham) water for 10 s. The ACE group was treated with
      intraperitoneal 10 mg/kg captopril immediately after burn and this treatment was
      repeated twice daily. At the end of the 24 h brain samples were taken. nNOS was
      studied in brain areas by immunohistochemistry. RESULTS: There was no difference
      between the cerebellar and hypothalamic areas the nNOS expression of all groups.
      nNOS expression increased in the frontal cortex, striatum and midbrain in the
      burn group compared to the control group. In the frontal cortex, nNOS expression
      significantly decreased after ACE inhibitor treatment (p<0.05). The striatal nNOS
      of the ACE group significantly increased when compared to the control group
      (p=0.001). In the midbrain of the animals, nNOS decreased in the ACE group.
      Hippocampal nNOS expression did not change after burn and significantly increased
      after ACE inhibitor therapy (p<0.05). CONCLUSIONS: Our data showed that the
      pathophysiological events following burn appear to be related to an acute
      inflammatory reaction which is associated with nNOS in the frontal cortex,
      striatum and midbrain, and captopril treatment abrogates the nNOS response in the
      frontal cortex and midbrain.

PMID- 23137629
TI  - Plagiarism and copyright violation: two things in common.

PMID- 23137628
TI  - Cause of death and correlation with autopsy findings in burns patients.
AB  - OBJECTIVE: Global mortality from burns is decreasing however there is a relative
      paucity of mortality data in the literature from burns units in the United
      Kingdom. We present an analysis of burns deaths and correlation with coroners'
      autopsy findings from a large regional burns unit. DESIGN: Retrospective medical
      note review of patients who died over a 7 year period (January 2005 to April
      2011) was undertaken. Patient demographics were recorded in addition to: burn
      size, depth, length of stay, presence of inhalational injury, organs failing and
      diagnosis of sepsis. In order to evaluate the accuracy of our pre-mortem clinical
      diagnosis, we compared post-mortem cause of death with clinical cause of death.
      RESULTS: There were 92 deaths out of 4745 admissions for acute burn (crude
      mortality 1.9%). 37 patients were immediately given comfort care and excluded
      from analysis. Average age was 52.9 years+/-19.4, average percentage burn 43.7%+/
      26.8, and length of stay 26.4+/-45 days. 80% of deaths were attributable to flame
      burn (44/55), and 51% (28/55) suffered inhalational injury. Multi-organ failure
      was the primary cause of death (39/55), with sepsis being the primary trigger
      (20/39, 51%). Pseudomonas was the most common organism isolated in septic
      patients. There were significant difficulties in obtaining post-mortem reports
      and an obvious lack of correlation between coroners' reports and clinical cause
      of death. CONCLUSIONS: The principal cause of mortality in our unit was multi
      organ failure due to sepsis, which concurs with current literature. Autopsy has
      previously been shown to be a useful retrospective diagnostic tool, however we
      challenge its reliability as a result of our study.

PMID- 23137630
TI  - Retinal pigment epithelial cell loss assessed by fundus autofluorescence imaging
      in neovascular age-related macular degeneration.
AB  - PURPOSE: To characterize retinal pigment epithelial (RPE) cell loss as evidenced
      by autofluorescence imaging in patients with neovascular age-related macular
      degeneration (AMD). DESIGN: Retrospective cohort study. PARTICIPANTS: There were
      162 eyes of 116 consecutive patients with neovascular AMD examined in a retinal
      practice. METHODS: Each patient underwent a complete examination including
      autofluorescence imaging. Areas of confluent absence of autofluorescence signal
      of at least 0.5 mm in greatest linear diameter were measured within the macular
      area. Patient demographic and examination data were evaluated in relation to the
      autofluorescence data. MAIN OUTCOME MEASURES: Prevalence and progression of
      confluent areas of absent autofluorescence and the relationship these areas had
      with visual acuity. RESULTS: The mean age of the patients was 82.9 years, and the
      mean visual acuity was 20/71 (logarithm minimum angle of resolution [logMAR],
      0.55). Confluent loss of autofluorescence was seen in 58.6% of eyes at baseline,
      and the median area of absent autofluorescence among those was 1.57 mm(2)
      (interquartile range [IQR], 0.62-4.32 mm(2)). Using generalized estimation
      equation modeling, the significant predictors for area of confluent absent
      autofluorescence at baseline were duration of disease and any previous treatment
      with photodynamic therapy. The significant predictor of baseline visual acuity
      was baseline area of confluent absent autofluorescence. Follow-up was available
      for 124 (76.5%) eyes, with a mean follow-up of 2.9 years. By then, the mean
      visual acuity was 20/90 (logMAR, 0.65), and 79% of eyes had confluent areas of
      absent autofluorescence, the large majority of which affected the central macula.
      The median area of absent autofluorescence was 3.61 mm(2) (IQR, 1.16-7.11 mm(2)).
      The best predictor of final visual acuity was the area of absent autofluorescence
      at the final follow-up. CONCLUSIONS: Confluent absence of autofluorescence, a
      measure signifying RPE loss, was a significant predictor of visual acuity both at
      baseline and at final follow-up. This is the first study to document the
      prevalence, rate of progression, and factors associated with measures of
      confluent RPE loss in patients with neovascular AMD. Application of strategies to
      limit RPE cell loss may prove useful in eyes with neovascular AMD.

PMID- 23137631
TI  - Association of eNOS polymorphisms (-786T>C, 4a4b, 894G>T) with colorectal cancer
      susceptibility in the Korean population.
AB  - BACKGROUND: Polymorphisms of endothelial nitric oxide synthases (eNOS) have been
      shown to be associated with cancer susceptibility. However, the results of such
      studies are conflicting to date. We investigated whether polymorphisms of the
      eNOS gene correlated with patients with colorectal cancer (CRC), relative to
      healthy individuals. PATIENTS AND METHODS: In the present study, we analyzed
      three polymorphisms of eNOS (-786T>C, 4a4b, and 894G>T) in 509 healthy controls
      and 528 patients with CRC. The genotyping of eNOS polymorphisms was performed
      using polymerase chain reaction or polymerase chain reaction-restriction fragment
      length polymorphism assays. RESULTS: We found that the TC+CC genotype of the 
      786T>C polymorphism was significantly associated with an increased risk of CRC
      compared with the TT genotype. Similarly, the GT+TT genotype of the 894G>T
      polymorphism was associated with an increased susceptibility to CRC. However, no
      evidence was found for any association between the 4a4b polymorphism and CRC
      risk. In addition, the C/4b/G (-786T>C/4a4b/894G>T) haplotype was significantly
      associated with increased risk of CRC and C/4b/T (-786T>C/4a4b/894G>T) haplotype
      was only detected in CRC patients. CONCLUSIONS: Our study suggests that the eNOS 
      786T>C and 894G>T polymorphisms may be associated with the development of CRC in
      the Korean population.

PMID- 23137632
TI  - Identification and in silico analysis of a novel troponin C like gene from
      Ruditapes philippinarum (Bivalvia: Veneridae) and its transcriptional response
      for calcium challenge.
AB  - Troponin C (TnC) is one of the subunits composing the troponin complex, which is
      primarily expressed in muscle tissue and plays a major role in regulating
      contractility. We have identified a novel TnC-like gene (RpTnC) from the
      Ruditapes philippinarum Manila clam. Sequence analysis indicated that RpTnC has a
      450bp coding sequence, encoding a 150 amino acid protein with a molecular mass of
      17.4 kDa. The RpTnC protein consisted of four EF-hand motifs (I-IV), each with a
      Ca2+-binding site. In silico comparative analysis of protein sequence showed that
      only site IV, demonstrating a conserved stretch (DxDxSx6E), is functionally
      active for Ca2+-coordination. Moreover, RpTnC was homologically (61.3% identity)
      and phylogenetically closest to Japanese flying squid TnC. The mRNA expression
      analysis using quantitative real-time PCR revealed a differential basal
      expression of RpTnC transcripts in six different clam tissues, with higher levels
      in adductor muscle and mantle. Intramuscular administration of CaCl2 caused a
      prominent upregulation of RpTnC transcripts in adductor muscle (~5 fold).
      Collectively, our findings suggest that the TnC homolog of Manila clam identified
      in this study may be involved in important role(s) in clam physiology, mainly in
      its muscle tissues, and its transcription could be significantly influenced by
      increased Ca2+ levels.

PMID- 23137633
TI  - Polymorphisms in the IL-18 and IL-12B genes and their association with the
      clinical outcome in Croatian patients with Type 1 diabetes.
AB  - Genetic variants of IL-18 and IL-12B may be important in immunoregulatory
      abnormalities, observed in the patients with Type 1 diabetes mellitus (T1DM),
      that contribute to individual differences in response to a treatment. Therefore,
      we examined the significance of IL-18-137G/C, IL-18-607C/A, and IL-12B A/C
      polymorphisms in Croatians (187 patients, 236 controls), not only as factors that
      contribute to susceptibility to T1DM, but also as determinants of the clinical
      presentation of disease. The polymorphism screening has been performed using PCR
      sequence-specific primers (IL-18) or PCR-RFLP (IL-12B) approach. Results were
      evaluated by GraphPad Prism and Sigma Stat 3.5, Arlequin software and calculator
      for Hardy-Weinberg equilibrium. The genotype, allele and haplotype distribution
      were not statistically different between the patients and control subjects. The
      clinical parameter analysis revealed that patients with minor alleles at each
      locus, IL-18-137C/-607A, were significantly younger at T1DM onset than carriers
      of major alleles, IL-18-137G/-607C (20 vs 23.5 years). Moreover, the concomitant
      presence of minor alleles not only of IL-18 but also of IL-12B, is associated
      with the risk of disease progression even at younger age. These patients
      developed diabetes at 16 years of age, what is significantly earlier (p=0.044)
      compared to 25.5 years of age in patients with common alleles IL-18-137G/-607C/IL
      12B A. Furthermore, combined genotype analysis of IL-18 and IL-12B has pointed
      out that patients with CC/AA/AA genotype have the worst glucose control based on
      HbA1c (8.7%, range 6.8-13.1%). In conclusion, susceptibility to T1DM in Croatians
      is not strongly associated with IL-18-137/-607 and IL-12B polymorphisms. These
      SNPs are associated with the higher risk of earlier disease development and might
      be implicated in the effectiveness of glycemic control.

PMID- 23137635
TI  - Structural organization and classification of cytochrome P450 genes in flax
      (Linum usitatissimum L.).
AB  - Flax CYPome analysis resulted in the identification of 334 putative cytochrome
      P450 (CYP450) genes in the cultivated flax genome. Classification of flax CYP450
      genes based on the sequence similarity with Arabidopsis orthologs and CYP450
      nomenclature, revealed 10 clans representing 44 families and 98 subfamilies.
      CYP80, CYP83, CYP92, CYP702, CYP705, CYP708, CYP728, CYP729, CYP733 and CYP736
      families are absent in the flax genome. The subfamily members exhibited conserved
      sequences, length of exons and phasing of introns. Similarity search of the
      genomic resources of wild flax species Linum bienne with CYP450 coding sequences
      of the cultivated flax, revealed the presence of 127 CYP450 gene orthologs,
      indicating amplification of novel CYP450 genes in the cultivated flax. Seven
      families CYP73, 74, 75, 76, 77, 84 and 709, coding for enzymes associated with
      phenylpropanoid/fatty acid metabolism, showed extensive gene amplification in the
      flax. About 59% of the flax CYP450 genes were present in the EST libraries.

PMID- 23137634
TI  - Molecular cloning and functional characterization of an endogenous endoglucanase
      belonging to GHF45 from the western corn rootworm, Diabrotica virgifera
      virgifera.
AB  - A novel insect beta-1,4-endoglucanase (DvvENGaseI) gene belonging to the
      glycoside hydrolase family (GHF) 45 was identified from the western corn
      rootworm, Diabrotica virgifera virgifera. The cDNA of the DvvENGaseI consisted of
      a 720 bp open reading frame encoding a 239 amino-acid protein. Analysis of the
      amino acid sequence revealed that DvvENGaseI exhibits 60% protein sequence
      identity when compared with an endoglucanase belonging to GHF45 from another
      beetle, Leptinotarsa decemlineata. Western blot analyses using a polyclonal
      antiserum developed from a partial peptide sequence revealed that DvvENGaseI
      expression coincided with body regions corresponding to the fore-, mid- and
      hindgut, although regions corresponding to the midgut and hindgut were the
      primary sites for DvvENGaseI expression. Functional analysis of the DvvENGaseI by
      RNA interference (RNAi) indicated that nearly complete knock-down of gene
      expression could be obtained by injection of dsRNA based on qRT-PCR and western
      blot analysis. However, suppression only resulted in slight developmental delays
      suggesting that this gene may be part of a larger system of cellulose degrading
      enzymes.

PMID- 23137636
TI  - Association between osteoporosis and polymorphisms of the bone Gla protein,
      estrogen receptor 1, collagen 1-A1 and calcitonin receptor genes in Turkish
      postmenopausal women.
AB  - In this study, we have investigated the association between osteoporosis and
      osteocalcin (BGLAP) -298 C>T, estrogen receptor 1 (ER1) 397 T>C, collagen type1
      alpha 1 (Col1A1) 2046 G>T and calcitonin receptor (CALCR) 1340 T>C polymorphisms.
      Genomic DNA was obtained from 266 persons (158 osteoporotic and 108 healthy
      controls). Genomic DNA was extracted from EDTA-preserved peripheral venous blood
      of patients and controls by a salting-out method and analyzed by PCR-RFLP. As a
      result, there was no statistically significant difference in the genotype and
      allele frequencies of patients and controls for BGLAP -298 C>T, Col1A1 2046 G>T,
      ER1 397 T>C and CALCR 1340 T>C polymorphisms. However, ER1 CC genotype compared
      with TT+TC genotypes was found to increase the two fold the risk of osteoporosis
      [p=0.039, OR=2.156, 95% CI (1.083-4.293)] and CALCR CC genotype compared with
      TT+TC genotypes was found to have protective effect against osteoporosis
      [p=0.045, OR=0.471, 95% CI (0.237-0.9372)]. In the combined genotype analysis,
      ER1/CALCR TCCC combined genotype was estimated to have protective effect against
      osteoporosis [p=0.0125, OR=0.323, 95% CI (0.1383-0.755)] whereas BGLAP/Col1A1
      CCTT and ER1/CALCR CCTT combined genotypes were estimated as risk factors for
      osteoporosis in Turkish population (p=0.027, p=0.009 respectively).

PMID- 23137637
TI  - Regulation of CEP131 gene expression by SP1.
AB  - Centrosomal proteins play important roles in cell cycle. Among them, the
      centrosomal protein of 131kDa (CEP131) has been reported as a critical factor for
      cilia formation which is related with development, signaling, and various
      diseases, the malfunction of cilia leading to cancer. Specificity protein 1
      (SP1), known as a centrosome regulator, is an essential transcription factor
      regulating the genes involved in multiple cellular processes such as cell cycle,
      apoptosis, and DNA damages. In this study, we explored the crucial role of SP1 in
      the regulation of CEP131 gene transcription. A deletion analysis of the CEP131
      promoter region revealed dominant promoter elements within the sequence between 
      400bp and -200bp, which contained consensus binding sites for SP1.
      Electrophoretic mobility shift assay (EMSA) and chromatin immuno-precipitation
      (ChIP) assay further confirmed the direct binding of SP1 to the CEP131 promoter.
      On the other hand, CEP131 transcription could be inhibited by mithramycin (a GC
      rich region inhibitor), but exogenous expression of SP1 could increase CEP131
      expression as evidenced by a reporter gene assay. In addition, mutation of
      several SP1 binding sites revealed four SP1 binding sites at -244/-225, -258/
      239, -304/-283 and -323/-304 that strongly affect CEP131 expression. Hence, it is
      suggested that SP1 is a pivotal transcription factor for the regulation of CEP131
      expression, consequently leading the control of centrosome functions.

PMID- 23137638
TI  - ZBTB38 gene polymorphism associated with body measurement traits in native
      Chinese cattle breeds.
AB  - Body measurement traits, influenced by genes and environmental factors, play
      numerous important roles in the value assessment of productivity and economy. In
      this study, we investigated the association between genetic polymorphisms of the
      zinc finger and BTB domain containing 38 gene (ZBTB38) and body measurement
      traits in native Chinese cattle. Using direct DNA sequencing in 423 individuals
      of 8 different cattle subpopulations, 9 novel polymorphisms were identified for
      genotyping within 647 bp region of exon 1 of ZBTB38. Linkage disequilibrium and
      association analysis revealed that two coding exon polymorphisms (2323 G>A and
      2325 C>T polymorphisms), missense mutations valine GTC(T) to isoleucine ATC(T),
      were associated with body length (BL), withers height (WH) and rump length (RL).
      Furthermore, the analysis of 2323 G>A and 2325 C>T SNP markers shows that there
      are significant effects on the BL (P=0.0488), WH (P=0.0044) and RL (P=0.0314) in
      the total population. These results clearly suggest that the ZBTB38 gene is among
      the target genes for body measurement traits in bovine breeding, and provide data
      for establishment of an animal model using cattle to study big animal body type.

PMID- 23137639
TI  - Iron-sulfur cluster scaffold (ISCU) gene is duplicated in salmonid fish and
      tissue and temperature dependent expressed in rainbow trout.
AB  - The iron-sulfur cluster protein ISCU is a scaffold protein tasked with the
      building and mediation of iron-sulfur [Fe-S]-clusters. These are crucial for [Fe
      S]-enzymes, which are involved in essential biological cell processes like
      metabolism or ion transport. Analysis of ISCU in rainbow trout (Oncorhynchus
      mykiss) and maraena whitefish (Coregonus maraena) revealed the existence of two
      gene variants in each of the two salmonids. This study presents the
      characterization of the duplicated ISCU cDNA sequences in both species as well as
      the comparative functional analysis of the genes in healthy and affected fish of
      two rainbow trout strains differing in trait robustness under regional
      aquaculture conditions. Coding sequences of trout ISCUA and ISCUB genes are
      spanning over five exons. Open reading frames (ORF) of trout (ISCUA: 495bp,
      ISCUB: 498bp) and whitefish (ISCUA and ISCUB: 495bp) genes encode for
      evolutionary highly conserved proteins and share 72% sequence similarity with
      human ISCU. Transcriptome analyses comparing healthy fish of the local rainbow
      trout strain BORN and the import strain TCO revealed strain-specific expression
      patterns for ISCU. Expression analyses by quantitative RT-PCR indicated
      remarkable differences between the transcript level of the gene variants ISCUA
      and ISCUB. Moderate temperature challenge (8 degrees C and 23 degrees C) suggests
      a generally higher transcript level of the two gene variants at 8 degrees C in
      the liver, spleen, and gill of both strains. However, no remarkable differences
      between the strains occurred in the temperature-dependent ISCU gene expression
      profiles. The experimental infection with Aeromonas salmonicida resulted in a
      different ISCU gene expression in the gill and trunk kidney of both strains after
      two weeks, suggesting a specific role of the scaffold gene in rainbow trout
      strain BORN, regarding the recovery after infection. Although results partially
      reflect the expected strain- and tissue-specific ISCUA and ISCUB regulation in
      rainbow trout, the data do not support the assumed association of ISCU with the
      trait robustness.

PMID- 23137640
TI  - Extra-vascular dissection of the pelvic sidewall for advanced cancers of the
      pelvis. A technique to obtain wider lateral resection margins.

PMID- 23137641
TI  - Transgastric cyst-gastrostomy for pancreatic pseudocyst.

PMID- 23137642
TI  - Ventral hernia repair in a potentially septic milieu.
AB  - Repair of the abdominal wall is the last stage of abdominal surgery; pariet
      complications, particularly infection, can have serious impact on operative
      results. While abdominal wound infections are not universally preventable, they
      are often predictable; the aphorism of Jean Rives (Stoppa, 1999 [1]) summarizes
      this sequence: "Infection is the mother of postoperative incisional hernia and
      infection of the incisional hernia repair is the grand-daughter". Repair of the
      abdominal wall in a potentially septic milieu requires the solution of an
      equation involving four variables: mechanism of sepsis, its severity, the
      surgical approach, and choice of prosthetic material. These interdependent
      variables potentiate each other, requiring adaptations of surgical strategy that
      cannot be absolutely determined pre-operatively, even with collegial
      consultation.

PMID- 23137643
TI  - Management of voluminous abdominal incisional hernia.
AB  - Incisional hernia is one of the classic complications after abdominal surgery.
      The chronic, gradual increase in size of some of these hernias is such that the
      hernia ring widens to a point where there is a loss of substance in the abdominal
      wall, herniated organs can become incarcerated or strangulated while poor
      abdominal motility can alter respiratory function. The surgical treatment of
      small (<5 cm) incisional hernias is safe and straightforward, by either
      laparotomy or laparoscopy. For large hernias, surgical repair is often difficult.
      After reintegration of herniated viscera into the abdominal cavity, the abdominal
      wall defect must be closed anatomically in order to restore the function to the
      abdominal wall. Prosthetic reinforcement of the abdominal wall is mandatory for
      long-term successful repair. There are multiple techniques for prosthetic hernia
      repair, but placement of Dacron mesh in the retromuscular plane is our
      preference.

PMID- 23137644
TI  - A review of available prosthetic material for abdominal wall repair.
AB  - Abdominal wall incisional and inguinal hernia repair can call for utilization of
      implants or prostheses as an alternative to simple suture techniques. The various
      implants can be synthetic, biologic or mixed: their physicochemical properties
      condition the mechanical results and the long-term outcome of the repair. The
      increasing number of available materials allows the surgeon to choose between a
      wide variety depending on the indication, the site of implantation, the surgical
      approach and whether the operative field is contaminated or not. With regard to
      evidence-based medicine, while several synthetic implants have been shown to be
      superior in efficacy to simple suture, other studies are underway to develop the
      indications for bioprostheses, in particular in contaminated fields. This review
      of the literature summarizes the current knowledge on synthetic and biologic
      implants (physicochemical characteristics, forms, indications).

PMID- 23137645
TI  - Hernia surgery. Introduction.

PMID- 23137646
TI  - Laparoscopic treatment of incisional hernia. State of the art in 2012.
AB  - OBJECTIVE: The objective of this review is to evaluate the results of
      laparoscopic treatment of ventral hernias using intra-peritoneal prosthetic mesh
      through a review of published surgical series. METHODS: All large series of
      patients treated for an incisional hernia by laparoscopy and published between
      2002 and 2011 were identified. The results of controlled randomized series
      comparing this technique with open surgical repair were analyzed. RESULTS: Twenty
      two series with a total of 7057 patients were analyzed (range 51-1242); the mean
      Body Mass Index (BMI) was 32 (range: 28.5-46), and the mean size of the hernia
      defect was 10.6 cm (range: 6-14.9 cm). The mean rate of conversion to open
      surgical repair was 2.7%. Mean operative duration was 90 +/- 33 minutes.
      Mortality was 0.8%, usually due to an unrecognized intestinal injury (1.6%),
      which occurred more frequently with second or iterative hernia repairs. Hospital
      stay averaged 2.5 days. The infection rate was 0.3% and the rate of hernia
      recurrence was 4.6% (with a mean follow-up of 36 months). No statistically
      significant differences were found in terms of post-operative complications or
      hernia recurrence in the randomized studies comparing laparoscopic to open
      anterior abdominal surgical repair. However, duration of hospital stay was
      shorter after laparoscopy in some studies. CONCLUSION: Laparoscopic repair of
      ventral incisional hernia is technically feasible and reliable for large hernia
      defects, even in obese patients. This approach should be reserved for patients
      with no history of previous hernia repair in order to avoid the risk of
      intestinal injury. It appears to allow for a shortened duration of
      hospitalization.

PMID- 23137647
TI  - Phylogeography of swine influenza H3N2 in the United States: translational public
      health for zoonotic disease surveillance.
AB  - The field of phylogeography has received a lot of attention for its application
      to molecular evolution and geographic migration of species. More recent work has
      included infectious diseases especially zoonotic RNA viruses like influenza and
      rabies. Phylogeography of viruses has the potential to advance surveillance at
      agencies such as public health departments, agriculture departments, and wildlife
      agencies. However, little is known about how these agencies could use
      phylogeography for applied surveillance and the integration of animal and human
      sequence data. Here, we highlight its potential to support 'translational public
      health' that could bring sequence data to the forefront of surveillance. We focus
      on swine influenza H3N2 because of the recent link to a variant form that has
      also infected humans. We discuss the implications to applied surveillance and the
      need for an integrated biomedical informatics approach for adoption at agencies
      of animal and public health.

PMID- 23137648
TI  - The low binding affinity of ADAMTS4 for citrullinated fibronectin may contribute
      to the destruction of joint cartilage in rheumatoid arthritis.
AB  - OBJECTIVES: Rapid cartilage degradation in the joints is observed in rheumatoid
      arthritis (RA). ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin
      motifs-4) degrades aggrecan, the primary component of cartilage, therefore
      contributing to joint erosion in RA. The proteolytic activity of ADAMTS4 is
      inhibited by fibronectin (FN). FN is abundantly expressed in the synovia in RA
      and is modified by citrullination, the conversion of peptidylarginine to
      citrulline. This study aims to investigate the binding ability of citrullinated
      FN (cFN) to ADAMTS4 and the effect of cFN on aggrecanase activity. METHODS: The
      full-length recombinant ADAMTS4 was purified from HEK293 cells that were
      transiently transfected with a full-length cDNA coding for human ADAMTS4. A 40
      kDa FN fragment exhibiting heparin binding was citrullinised with rabbit
      peptidylarginine deaminase. The binding activity of the full-length recombinant
      ADAMTS4 to cFN was investigated in an in vitro binding assay. The proteolytic
      activity of ADAMTS4 after incubation with cFN was determined using an aggrecanase
      activity kit, in which the ARGSVIL peptide is produced by digestion with
      aggrecanase. RESULTS: cFN displayed significantly decreased binding activity with
      ADAMTS4 compared with FN. The full-length ADAMTS4 produced large amounts of the
      ARGSVIL peptide, but the amount was markedly decreased in the presence of FN. The
      production of this peptide approached the normal level when the full-length
      ADAMTS4 was incubated with cFN. CONCLUSIONS: FN following citrullination is less
      effective in inhibiting the proteolytic activity of ADAMTS4. It is known that
      PADI4, an enzyme active in citrullination, is highly expressed in the synovial
      tissue in RA. Our results suggest that PADI4 in the RA synovium may contribute to
      cartilage destruction via the citrullination of FN.

PMID- 23137649
TI  - nm23-H1 is a negative regulator of TGF-beta1-dependent induction of epithelial
      mesenchymal transition.
AB  - Members of transforming growth factor-beta(TGF-beta) family are the main inducers
      of epithelial-mesenchymal transition (EMT) during embryogenesis and cancer
      pathogenesis. However, a significant crosstalk between TGF-beta and other signals
      occurs during the induction of EMT. nm23-H1 was the first metastasis suppressor
      gene to be identified on the basis of an inverse relationship between nm23-H1
      expression and metastasis stage. Despite extensive studies, the mechanism
      underlying its ability to suppress metastasis is far from elucidated. We
      demonstrated here that the nm23-H1 negatively regulated TGF-beta1-dependent
      induction of EMT in non-aggressive lung cancer cell line. nm23-H1 knockdown
      significantly enhanced TGF-beta1-induced suppression of epithelial marker E
      cadherin and upregulation of mesenchymal markers beta-catenin and fibronectin.
      The invasive and migratory potential of lung cancer cells upon TGF-beta1
      treatment was also markedly enhanced by nm23-H1 knockdown. On the other hand, the
      effect of nm23-H1 depletion on TGF-beta1-induced EMT was reversed by ectopic re
      expression of shRNA-resistant nm23-H1 protein. Furthermore, TGF-beta1-induced EMT
      potentiated by nm23-H1 depletion was partially dependent on transcriptional
      factor Snail expression. Finally, we found Src kinase is involved in regulation
      of TGF-beta1-induced EMT by nm23-H1. Our results suggest a means of restoring
      nm23-H1 to suppress TGF-beta1-induced EMT that may exploited therapeutically for
      the management of metastasis diseases.

PMID- 23137652
TI  - Advantages and limitations of brain imaging methods in the research of absence
      epilepsy in humans and animal models.
AB  - The purpose of this review is to analyze research possibilities and limitations
      of several methods, technical tools and their combinations for elucidation of
      absence epilepsy mechanisms, particularly the childhood absences. Despite the
      notable collection of simultaneous recording of clinical electroencephalography
      (EEG) and behavioral changes in relation to absence seizures, shortcomings of
      scalp EEG in both spatial resolution and precise detection of subcortical centers
      have limited the understanding of the fundamental mechanisms of altered brain
      function during and after recurrent epileptic paroxysms. Therefore, in the past
      decade, EEG recordings have often been combined with simultaneous imaging methods
      in epilepsy studies. Among imaging methods, the following ones are used
      regularly: functional magnetic resonance imaging (fMRI), positron-emission
      tomography (PET), low-resolution electromagnetic tomography (LORETA), single
      photon emission spectroscopy (SPECT), near-infrared spectroscopy (NIRS), and
      optical imaging of intrinsic signals (IOS). In addition, voltage-sensitive dye
      optical imaging method and even photoacoustic microscopy can be applied to animal
      models of epilepsy. Samplings of some of the most relevant data obtained by the
      above methods are presented. It appears that the elaboration of more adequate
      animal models of the patterns of absence seizures during the early postnatal
      period is necessary for better correspondence of human and animal absence
      phenomena.

PMID- 23137651
TI  - The anatomy of fronto-occipital connections from early blunt dissections to
      contemporary tractography.
AB  - The occipital and frontal lobes are anatomically distant yet functionally highly
      integrated to generate some of the most complex behaviour. A series of long
      associative fibres, such as the fronto-occipital networks, mediate this
      integration via rapid feed-forward propagation of visual input to anterior
      frontal regions and direct top-down modulation of early visual processing.
      Despite the vast number of anatomical investigations a general consensus on the
      anatomy of fronto-occipital connections is not forthcoming. For example, in the
      monkey the existence of a human equivalent of the 'inferior fronto-occipital
      fasciculus' (iFOF) has not been demonstrated. Conversely, a 'superior fronto
      occipital fasciculus' (sFOF), also referred to as 'subcallosal bundle' by some
      authors, is reported in monkey axonal tracing studies but not in human
      dissections. In this study our aim is twofold. First, we use diffusion
      tractography to delineate the in vivo anatomy of the sFOF and the iFOF in 30
      healthy subjects and three acallosal brains. Second, we provide a comprehensive
      review of the post-mortem and neuroimaging studies of the fronto-occipital
      connections published over the last two centuries, together with the first
      integral translation of Onufrowicz's original description of a human fronto
      occipital fasciculus (1887) and Muratoff's report of the 'subcallosal bundle' in
      animals (1893). Our tractography dissections suggest that in the human brain (i)
      the iFOF is a bilateral association pathway connecting ventro-medial occipital
      cortex to orbital and polar frontal cortex, (ii) the sFOF overlaps with branches
      of the superior longitudinal fasciculus (SLF) and probably represents an
      'occipital extension' of the SLF, (iii) the subcallosal bundle of Muratoff is
      probably a complex tract encompassing ascending thalamo-frontal and descending
      fronto-caudate connections and is therefore a projection rather than an
      associative tract. In conclusion, our experimental findings and review of the
      literature suggest that a ventral pathway in humans, namely the iFOF, mediates a
      direct communication between occipital and frontal lobes. Whether the iFOF
      represents a unique human pathway awaits further ad hoc investigations in
      animals. 

PMID- 23137650
TI  - Contributions of microRNA dysregulation to cisplatin resistance in adenocarcinoma
      cells.
AB  - Cisplatin resistance in cancer cells is due to a pleiotropic phenotype transition
      that allows cells to resist cell death. miRNAs have been shown to be reliable
      markers of phenotype, critical in cell differentiation, and dysregulated in
      cancer and other pathologies. Here we investigate the influence of miRNA on
      cisplatin resistance in KB adenocarcinoma cells. Silencing both DICER and TRBP2
      in the miRNA biosynthesis pathway in KB-3-1 (sensitive parental), KB-CP.5
      (cisplatin-resistant), and KB-CP20 (highly cisplatin-resistant) cells resulted in
      the reversal of cisplatin resistance, with no effect on cell viability in the
      absence of cisplatin. We found miR-181 expression differences in the cell lines
      using RT-PCR, with several members of the miR-181 family overexpressed in two KB
      cisplatin-resistant lines and in two cisplatin-resistant lung cancer lines,
      compared to their respective parental cells. Functional assays showed minimal
      effects of miR-181 on cisplatin resistance. We conclude that the miRNA
      biosynthesis pathway is critical for maintaining the cisplatin-resistant
      phenotype, but that it is difficult to determine the precise miRNAs involved in
      cisplatin resistance simply using expression profiles of individual miRNA
      species. Functional assays are needed to determine the influence of a specific
      miRNA and different members of the same miRNA family may have opposite effects.

PMID- 23137653
TI  - Sigmoid fits to locate and characterize cortical boundaries in human cerebral
      cortex.
AB  - Quantitative evaluation of neuropathology within the cortex often requires a
      significant investigator time commitment. Here we elaborate on a method of
      quantifying the distinctiveness of the gray-white matter boundary using function
      fitting methods (Avino and Hutsler, 2010) and demonstrate that it can also be
      adapted to reliably identify the location of the gray matter/white matter (GM-WM)
      boundary in microscopic images, even when that boundary is indistinct. Multiple
      images of the gray-white matter boundary were acquired from sixteen subjects.
      Density profiles across the cortical layers were acquired and sigmoid functions
      were iteratively fit to the density profiles until a best fit was found. The
      slope of the resulting sigmoid was used to describe both the position and
      distinctiveness of the GM-WM boundary. Subsequently, two raters laid cortical
      boundaries on the same set of images and agreement between the raters, as well as
      agreement between each rater and the transverse-based boundaries, was assessed.
      Computer-generated boundaries showed reliably higher agreement with each
      individual rater, relative to the agreement between individual raters. Error
      between the raters and the transverse-based boundaries was associated with those
      images where the boundary was less distinct as assessed by the sigmoid slopes.
      These findings suggest that transverse-based boundaries are superior to user
      generated boundaries. Furthermore, these findings suggest that rater-based
      boundary definitions in both neurotypical and pathological cases may become
      unreliable as the number of cell profiles found in the subplate region increases,
      as is the case in both autism and schizophrenia.

PMID- 23137654
TI  - Application of ultrasound to textiles washing in aqueous solutions.
AB  - The ultrasound was applied to textile washing as a mechanical action for soil
      removal. The polyester fabric was soiled with carbon black or oleic acid as a
      model contaminant, and washed with the original fabric in aqueous solutions
      without and with alkali or surfactant by applying ultrasound, shaking or stirring
      action. The detergency and soil redeposition were evaluated from the change in
      the surface reflectance of artificially soiled fabrics and the original fabric
      due to washing. In comparison with shaking and stirring actions, ultrasound was
      found to remove the particulate and oily soils efficiently in a short time and at
      low bath ratio. With increasing ultrasound power, the detergency of both soils
      increased and exceeded that obtained with Wascator, a horizontal axis drum type
      washer. Using three standard fabrics for determining mechanical action during
      washing, it was shown that ultrasound washing caused little mechanical damage to
      the fabric. However, the soil redeposition was frequently observed for ultrasonic
      washing, especially at low bath ratio.

PMID- 23137655
TI  - Kinetic sonication effects in light of molecular dynamics simulation of the
      reaction medium.
AB  - Molecular dynamics (MD) simulation of the structure of ethyl acetate solutions in
      two water-ethanol mixtures was performed at 280 and 330K. The MD simulations
      revealed that ethyl acetate was preferentially solvated by ethanol, water being
      mainly located in the next solvation layer. With increasing temperature ethanol
      was gradually replaced by water in the first solvation shell. These findings
      explain the decrease in the rate of ester hydrolysis with increasing molar ratio
      of ethanol in the solution as the reaction rate was linearly dependent on the
      relative ethanol content in the first solvation shell of the ester. Predominance
      of ethanol results in decreased polarity and water activity in the shell and
      accordingly in a decreased reaction rate. Based on the results of the MD
      simulations, the principal conclusion of this work is that ultrasound enhances
      the kinetic energy (the effective temperature) of species in the solution and, in
      this way, evokes shifts in the solvation equilibria thus affecting the reaction
      rate. It appears that ultrasound does not completely break down the solvent
      shells or clusters in the solution as previously believed. Phenomena of thermo
      solvatochromism and reaction rate levelling by ultrasound in binary solvents are
      described.

PMID- 23137656
TI  - A highly efficient magnetic solid acid catalyst for synthesis of 2,4,5
      trisubstituted imidazoles under ultrasound irradiation.
AB  - Fe(3)O(4) nanoparticles were prepared by chemical coprecipitation method and
      subsequently coated with 3-aminopropyltriethoxysilane (APTES) via silanization
      reaction. Grafting of chlorosulfuric acid on the amino-functionalized Fe(3)O(4)
      nanoparticles afforded sulfamic acid-functionalized magnetic nanoparticles (SA
      MNPs). SA-MNPs was found to be a mild and effective solid acid catalyst for the
      efficient, one-pot, three-component synthesis of 2,4,5-trisubstituted imidazoles
      under ultrasound irradiation. This protocol afforded corresponding imidazoles in
      shorter reaction durations, and in high yields. This green procedure has many
      obvious advantages compared to those reported in the previous literatures,
      including avoiding the use of harmful catalysts, easy and quick isolation of the
      products, excellent yields, short routine, and simplicity of the methodology.

PMID- 23137657
TI  - [Evaluation of the LightCycler(r) SeptiFast test in newborns and infants with
      clinical suspicion of sepsis].
AB  - INTRODUCTION: Neonatal sepsis is a significant cause of morbidity and mortality.
      Early diagnosis and prompt antimicrobial therapy are crucial for a favorable
      outcome of the newborn child. Blood culture, the current "gold standard" method
      for diagnosing bloodstream infections, has a low sensitivity in newborns. We
      evaluated the multiplex real-time PCR LightCycler((r)) SeptiFast (LC-SF) for
      detection of bloodstream infections in newborns, compared with conventional blood
      culture. METHODS: A total of 42 blood samples were obtained from 35 subjects
      presenting with a febrile episode and hospitalized in neonatal intensive care
      unit at Hospital Universitario Virgen de las Nieves. Two samples were collected
      during each febrile episode in order to carry out LC-SF assay and blood culture,
      respectively. RESULTS: Sensitivity and specificity of 79% and 87%, respectively,
      compared with clinical diagnosis, were obtained for LC-SF. Contamination rate of
      blood cultures was 16.7%, mainly due to coagulase-negative staphylococci (CoNS)
      and viridans groups of streptococci. Contamination rate of LC-SF by CoNS was
      2.4%. Concordance between LC-SF and blood culture was moderate (kappa index:
      0.369). LC-SF demonstrated a higher concordance (kappa index: 0.729) with the
      final clinical diagnosis than blood culture (kappa index: 0.238). CONCLUSION: LC
      SF assay could be a useful diagnostic tool, along with a conventional blood
      culture, in newborn, for confirming or ruling out those cases that blood culture
      could not determine, shortening the time to result to 7 hours.

PMID- 23137659
TI  - Disaster management in India: a road ahead.

PMID- 23137658
TI  - Platelet-derived growth factors and their receptors: structural and functional
      perspectives.
AB  - The four types of platelet-derived growth factors (PDGFs) and the two types of
      PDGF receptors (PDGFRs, which belong to class III receptor tyrosine kinases) have
      important functions in the development of connective tissue cells. Recent
      structural studies have revealed novel mechanisms of PDGFs in propeptide loading
      and receptor recognition/activation. The detailed structural understanding of
      PDGF-PDGFR signaling has provided a template that can aid therapeutic
      intervention to counteract the aberrant signaling of this normally silent
      pathway, especially in proliferative diseases such as cancer. This review
      summarizes the advances in the PDGF system with a focus on relating the
      structural and functional understandings, and discusses the basic aspects of
      PDGFs and PDGFRs, the mechanisms of activation, and the insights into the
      therapeutic antagonism of PDGFRs. This article is part of a Special Issue
      entitled: Emerging recognition and activation mechanisms of receptor tyrosine
      kinases. 

PMID- 23137660
TI  - Predicted drug-induced bradycardia related cardio toxicity using a zebrafish in
      vivo model is highly correlated with results from in vitro tests.
AB  - Several in vivo and in vitro studies have assessed methods of evaluating the
      cardio toxicity of compounds during drug development due to its importance for
      predicting human toxicity. However, in vivo/in vitro relationships have not yet
      been reported using a zebrafish model. This study determined the bradycardia of
      15 compounds by evaluating the change in heart beat rate (HBR) in zebrafish, hERG
      fluorescence polarization (hERG-FP), and ionic current change using a patch clamp
      (hERG-PC). In addition, a model for prediction of drug-induced bradycardia was
      established using in vivo and in vitro assays designed for high-throughput
      toxicological screening. The IC(50) values correlated well in two in vitro
      studies (R(2)=0.9). The change in HBR in zebrafish caused by the compounds could
      be estimated using the IC(50) from the hERG-FP assay [(i.e., % of
      HBR=19.5*log(IC(50), hERG-FP)] or hERG-PC assay [(i.e., % of HBR=19.6*log(IC(50),
      hERG-FP)]. To validate the predictive model, 10 unknown compounds were used and
      the percentages of the HBR were estimated using the model. The observed and
      predicted HBR% for the compounds in zebrafish were well-correlated (R(2)=0.948).
      Therefore, the proposed models were useful for prediction of drug-induced
      bradycardia related cardio toxicity.

PMID- 23137661
TI  - Toxoplasma gondii: enzyme-linked immunosorbent assay based on a recombinant multi
      epitope peptide for distinguishing recent from past infection in human sera.
AB  - Enzyme-linked immunosorbent assays (ELISAs) based on a recombinant multi-epitope
      peptide (rMEP) were used in an attempt to differentiate pregnant women with
      Toxoplasma serologic profiles (TSPs) indicative of recently acquired infections
      (acute profile) from those with TSPs indicative of infections acquired in the
      distant past (chronic profile). The recombinant expression vector pET-32c-MEP
      encoding MEP constructed previously was expressed in Escherichia coli and the
      rMEP was purified as a bioactive fusion protein. The IgG-ELISA and IgM-ELISA
      based on the purified rMEP were developed, and used to detect IgG and IgM
      antibodies against Toxoplasma gondii in human sera. Immunoblot assays showed that
      the purified rMEP could be strongly recognized by IgM antibodies in the pooled
      sera from women with acute profiles, and by IgG antibodies in the pooled sera
      from women with chronic profiles. ELISA results also proved that the reactivities
      of IgG and IgM antibodies differed significantly in sera from women with acute
      and chronic profiles. Compared with two commercial ELISA tests for seradiagnosis
      of toxoplasmosis, the total concordance (including positive and negative sera) of
      this rMEP-based assay was 93.2% and 95.7% for the detection of IgG and IgM
      antibodies, respectively. Our study suggests that the rMEP protein could be used
      as the diagnostic antigen to differentiate recent from past infections in human
      toxoplasmosis.

PMID- 23137662
TI  - Differences in spectral absorption properties between active neovascular macular
      degeneration and mild age related maculopathy.
AB  - This study examines the differences in spectral absorption properties between the
      maculae of patients with active neovascular macular degeneration and those with
      early age related maculopathy (ARM). Patients attending for management of
      neovascular age related macular degeneration (AMD) underwent multispectral
      imaging with a system comprising of a modified digital fundus camera coupled with
      a 250-W tungsten-halogen lamp and a liquid crystal fast-tuneable filter. Images
      were obtained at 8 wavelengths between 496 and 700 nm. Aligned images were used
      to generate a DLA (differential light absorption, a measure of spectral
      absorption properties) map of the macular area. DLA maps were generated for both
      eyes of 10 sequential patients attending for anti-vascular endothelial growth
      factor injections. Each of these patients had active leaking neovascular AMD in
      one eye and early ARM or milder disease in the fellow eye. Eyes with neovascular
      AMD demonstrated lower average levels of DLA compared with their fellow eyes with
      early ARM (p=0.037, t test). The significant difference in DLA demonstrates the
      potential of multispectral imaging for differentiating the two pathologies non
      invasively.

PMID- 23137663
TI  - Eye enucleations in Beijing Tongren Hospital in the last 50 years.

PMID- 23137664
TI  - Management of small choroidal melanocytic tumour.

PMID- 23137665
TI  - Femtosecond laser-assisted corneal transplantation.

PMID- 23137667
TI  - Predictive value of electrocorticography for postoperative epilepsy in patients
      with supratentorial meningioma.
AB  - This study examines electrocorticography (ECoG) signals in patients with
      supratentorial meningioma before and after tumor resection, and discusses its
      predictive value with regard to postoperative epilepsy. Ninety-one patients with
      supratentorial meningioma, who presented with seizures, were studied. Patients
      were followed-up for 2 to 5 years, and the occurrence rate of postoperative
      epilepsy in each group was compared. Depending on the frequency and amplitude
      variation in multiple spike waves on ECoG, patients were divided into those with
      an increase in epileptic discharge (Group A), those with no change (Group B), and
      those with a reduction in epileptic discharge (Group C). Postoperative seizures
      was classified as early postoperative seizures (within 1 week of surgery) or late
      postoperative seizures (> 1 week after surgery). After lesion resection and
      measurement of ECoG, the 91 patients were divided into Group A (12 patients,
      13.19%), Group B (36 patients, 39.56%) and Group C (43 patients, 47.25%). Of
      these 91 patients, 29 (31.87%) had early postoperative seizures of which seven
      patients (58.33%) were from Group A, 13 (36.11%) were from Group B and nine
      (20.93%) were from Group C (chi(2)=6.53, p<0.05). Seventeen patients (18.68%) had
      late postoperative seizures, of which two patients (16.67%) were from Group A,
      seven were from Group B (19.44%) and eight were from Group C (18.60%)
      (chi(2)=0.05, p>0.05). Of the 29 patients with early postoperative seizures,
      seven (24.14%) also had late postoperative epilepsy. Of the 62 patients who did
      not experience early postoperative seizures, 10 (16.13%) also had late
      postoperative epilepsy (chi(2)=0.83, p>0.05). Thus, the change in ECoG before and
      after resection in patients with supratentorial meningioma has a predictive value
      for early postoperative seizures.

PMID- 23137666
TI  - Fluorescence in situ hybridisation (FISH) in histologically challenging
      conjunctival melanocytic lesions.
AB  - BACKGROUND: Even in experienced hands, the classification of some melanocytic
      lesions of the conjunctiva remains challenging. In skin pathology, the recent
      application of fluorescence in situ hybridisation (FISH) has been demonstrated to
      be of use for the analysis and diagnosis of ambiguous melanocytic neoplasms of
      the skin. This study set out to evaluate this method on seven prospective
      conjunctival cases that were histologically equivocal. METHODS: 18 unequivocal
      retrospective melanocytic controls were exposed to FISH. Commercially available
      probes assessing copy numbers of RREB1 (6p25), MYB (6q23) and CCND1 (11q13) genes
      compared with CEP6 (a chromosome six centromeric reference point) were used.
      After control verification, seven prospective, equivocal cases were identified
      and exposed to FISH. RESULTS: There was complete correlation between FISH result
      and the control section histopathology report. Control cases of melanoma cases
      were all positive for FISH and control benign lesions were negative. Of the seven
      equivocal cases, five were positive and classed as invasive melanoma or melanoma
      in situ, one was negative and one tetraploid, classed as negative (these last two
      cases were classed as naevi with careful clinical observation). CONCLUSIONS: FISH
      is very useful in classifying equivocal conjunctival melanocytic lesions,
      especially those with atypical junctional activity and naevoid melanocytic
      proliferations of the conjunctiva.

PMID- 23137668
TI  - MIB-1 labeling index predicts recurrence in intraventricular central
      neurocytomas.
AB  - Despite the relatively low-grade of most central neurocytomas (CN), evidence
      suggests the existence of an aggressive subset with a propensity for recurrence.
      Recent studies have found the MIB-1 labeling index to be a prognostic indicator
      in CN. Here we review our experience with CN to analyze the relationships between
      extent of resection, adjuvant therapy, tumor histology, and clinical outcomes
      based on aggressive histology, as defined by MIB-1 labeling. A retrospective
      review was performed on histologically proven CN surgically resected from 1993 to
      2009 at the University of California at San Francisco. Recurrence rates were
      analyzed using the Kaplan-Meier method with respect to MIB-1 labeling and extent
      of resection. All MIB-1 labeling indices were analyzed. A total of 18 patients
      were identified with a mean age of 30 years (range 17-58 years) and median follow
      up of 40 months (5-173 months). The treatments were: gross total resection (GTR)
      alone (17% of patients), subtotal resection (STR) alone (50% of patients), STR
      plus radiotherapy (XRT: external beam or stereotactic radiosurgery: 28% of
      patients), or STR plus chemotherapy (5% of patients). The extent of resection and
      a MIB-1 labeling index >4% was predictive of recurrence (p<0.01). In the 33% of
      the patients in whom the tumor recurred, all had STR with MIB-1 labeling >4% with
      median time to recurrence of 23.5 months. The 2-year and 4-year recurrence rates
      in patients with MIB-1 labeling >4% were 50% and 75% respectively. No patient
      with a MIB-1 labeling index <4% who received STR alone had a recurrence. Thus, in
      patients with CN who were treated with STR, histology demonstrating a MIB-1
      labeling index >4% can be a clinically useful prognostic indicator and can help
      guide adjuvant treatment.

PMID- 23137669
TI  - Predictors of in-stent stenosis and occlusion after endovascular treatment of
      intracranial vascular disease with the Willis covered stent.
AB  - Covered stent placement has emerged as a promising therapeutic option for
      intracranial vascular lesions. However, in-stent stenosis and occlusion continue
      to be important concerns with the use of a covered stent, which is more
      thrombogenic than other types of stents. The purpose of this study was to
      determine predictors of in-stent stenosis and occlusion for covered stents used
      in the treatment of intracranial vascular diseases. Clinical, procedural and
      angiographic data of 46 patients with 49 intracranial vascular lesions treated
      with the Willis covered stent (Micro-Port, Shanghai, China) between April 2005
      and October 2010 were collected and analyzed retrospectively. Univariate analysis
      and multivariate logistic regression analysis were performed to determine the
      factors predictive of in-stent stenosis and/or occlusion of the stents. In-stent
      stenosis and/or occlusion were documented at angiography in six patients with six
      lesions, and no stenoses or occlusions were seen at angiography in the remaining
      40 patients with 43 lesions. Univariate analysis revealed that hypertension, post
      procedure irregular antiplatelet therapy and cerebrovascular arteriosclerosis
      were associated with in-stent stenosis and/or occlusion. By multivariate logistic
      regression analysis, post-procedure irregular antiplatelet therapy (odds ratio
      [OR]=15; 95% confidence interval [CI], 1.172-192.004; p=0.037) and
      cerebrovascular arteriosclerosis (OR=19; 95% CI, 1.374-262.659; p=0.028) were
      independent predictors of in-stent stenosis and/or occlusion. Thus, post
      procedure irregular antiplatelet therapy and coexistent cerebrovascular
      arteriosclerosis appear to increase the risk of in-stent stenosis and/or
      occlusion of covered stents in the treatment of intracranial vascular disease.

PMID- 23137670
TI  - In-vitro validation of a non-invasive dual fluoroscopic imaging technique for
      measurement of the hip kinematics.
AB  - Measurement of accurate in vivo hip joint kinematics in 6-DOF is difficult. Few
      studies have reported non-invasive measurements of the hip kinematics. The
      objective of this study was to validate a non-invasive dual fluoroscopic imaging
      system (DFIS) for measurement of hip kinematics. Bi-lateral hip joints of a
      cadaveric pelvic specimen were CT scanned to create bone models of the femur and
      pelvis, and subsequently tested in static and dynamic conditions inside the DFIS.
      The poses of the hip in space were then determined by matching the bone models
      with the fluoroscopic images. The pose data was compared to those obtained using
      a radio-stereometric analysis to determine the accuracy of the DFIS. The accuracy
      +/- precision for measuring the hip kinematics were less than 0.93 +/- 1.13 mm
      for translations and 0.59 +/- 0.82 degrees  for rotations in all conditions. The
      repeatability of the DFIS technique was less than +/- 0.77 mm and +/- 0.64
      degrees  in position and orientation for measuring hip kinematics in both static
      and dynamic positions. This technique could thus be a promising tool for
      determining 6-DOF poses of the hip during functional activities, which may help
      to understand biomechanical factors in hip pathologic conditions such as
      osteoarthritis and femoroacetabular impingement before and after surgical
      treatment.

PMID- 23137671
TI  - Stem cells in dentistry--Part II: Clinical applications.
AB  - New technologies that facilitate solid alveolar ridge augmentation are receiving
      considerable attention in the field of prosthodontics because of the growing
      requirement for esthetic and functional reconstruction by dental implant
      treatments. Recently, several studies have demonstrated potential advantages for
      stem-cell-based therapies in regenerative treatments. Mesenchymal stem/stromal
      cells (MSCs) are now an excellent candidate for tissue replacement therapies, and
      tissue engineering approaches and chair-side cellular grafting approaches using
      autologous MSCs represent the clinical state of the art for stem-cell-based
      alveolar bone regeneration. Basic studies have revealed that crosstalk between
      implanted donor cells and recipient immune cells plays a key role in determining
      clinical success that may involve the recently observed immunomodulatory
      properties of MSCs. Part II of this review first overviews progress in
      regenerative dentistry to consider the implications of the stem cell technology
      in dentistry and then highlights cutting-edge stem-cell-based alveolar bone
      regenerative therapies. Factors that affect stem-cell-based bone regeneration as
      related to the local immune response are then discussed. Additionally, pre
      clinical stem cell studies for the regeneration of teeth and other oral organs as
      well as possible applications of MSC-based immunotherapy in dentistry are
      outlined. Finally, the marketing of stem cell technology in dental stem cell
      banks with a view toward future regenerative therapies is introduced.

PMID- 23137672
TI  - A prosthodontic medicine with collaboration between medical and dental sciences.

PMID- 23137673
TI  - [CT screening for lung cancer].
AB  - Lung cancer is a common and serious disease, only early stage are curable. It is
      a logical candidate for a screening policy, especially as current and former
      smokers are easy to identify. The inefficiency of the chest radiograph is now
      proven, while the low-dose CT has shown promising data following a recent
      randomized study in North America. Yet, this is not specific and find a great
      number of benign anomalies. These limitations must be well known to physicians,
      radiologists and chest physicians if they use the individual screening.

PMID- 23137674
TI  - [Chronic lymphocytic leukemia in elderly patients].

PMID- 23137676
TI  - Transition metal-substituted cobalt ferrite nanoparticles for biomedical
      applications.
AB  - Transition metals of copper, zinc, chromium and nickel were substituted into
      cobalt ferrite nanoparticles via a sol-gel route using citric acid as a chelating
      agent. The microstructure and elemental composition were characterized using
      scanning electron microscopy combined with energy-dispersive X-ray spectroscopy.
      Phase analysis of transition metal-substituted cobalt ferrite nanoparticles was
      performed via X-ray diffraction. Surface wettability was measured using the water
      contact angle technique. The surface roughness of all nanoparticles was measured
      using profilometry. Moreover, thermogravimetric analysis and differential
      scanning calorimetry were performed to determine the temperature at which the
      decomposition and oxidation of the chelating agents took place. Results indicated
      that the substitution of transition metals influences strongly the
      microstructure, crystal structure and antibacterial property of the cobalt
      ferrite nanoparticles.

PMID- 23137675
TI  - Mouse liver-specific CD8(+) T-cells encounter their cognate antigen and acquire
      capacity to destroy target hepatocytes.
AB  - CD8(+) T-cell immune response to liver antigens is often functionally diminished
      or absent. This may occur via deletion of these autoaggressive T-cells, through
      the acquisition of an anergic phenotype, or via active suppression mediated by
      other cell populations. We generated a double transgenic model in which mice
      express CD8(+) T-cells specific for the lymphocytic choriomeningitis virus
      nucleoprotein (LCMV-NP) and LCMV-NP as a hepatic neo-autoantigen, to study the
      immunological response of potentially liver antigen autoaggressive CD8(+) T
      cells. Autoreactive transgenic CD8(+) T-cells were analyzed for functionality and
      cytotoxic effector status. Despite severe peripheral deletion of liver-specific
      CD8(+) T-cells, a fraction of autoreactive NP-specific CD8(+) T-cells accumulate
      in liver, resulting in hepatocyte injury and production of auto-antibodies in
      both male and female mice. NP-specific intrahepatic T-cells showed capacity to
      proliferate, produce cytokines and up-regulate activation markers. These data
      provide in vivo evidence that autoreactive CD8(+) T-cells are activated in the
      liver and developed an inflammatory process, but require additional factors to
      cause severe autoimmune destruction of hepatocytes. Our new model will provide a
      valuable tool for further exploration of the immunological response involved in
      inflammatory liver diseases, including autoimmune hepatitis.

PMID- 23137677
TI  - Leptin, adiponectin, resistin, visfatin serum levels and idiopathic recurrent
      pericarditis: biomarkers of disease activity? A preliminary report.
AB  - OBJECTIVES: Idiopathic recurrent acute pericarditis (IRAP) represents the most
      troublesome complication of acute pericarditis and is an autoimmune process.
      White adipose tissue produces more than 50 adipokines that participate in
      inflammation and autoimmunity. This study investigated whether serum leptin,
      resistin, visfatin and adiponectin are increased in IRAP versus healthy controls
      and if their levels correlate with parameters of disease activity. METHODS: Serum
      leptin, resistin, visfatin and adiponectin levels were assayed by enzyme-linked
      immunosorbent assay in 14 IRAP patients during recurrences (group 1), in 23 IRAP
      patients during symptom-free intervals (group 2) and in 18 healthy controls
      (group 3). Assessment parameters included demographic characteristics of patients
      and controls, clinical characteristics of patients and markers of inflammation.
      Comparisons between groups as well as reciprocal comparisons were evaluated.
      RESULTS: Group 1 showed serum leptin (p<0.008), visfatin (p<0.002), and
      adiponectin (p<0.04) significantly higher than group 2 and control group, whereas
      resistin serum levels did not significantly differ (p=0.69). Among IRAP patients,
      serum leptin significantly correlated with serum amyloid A (SAA) levels (rs=0.43,
      r2= 0.27, p<0.02). Other than this correlation, none of the considered adipokines
      significantly correlated with the other considered variables in univariate
      analysis. CONCLUSIONS: Leptin, adiponectin and visfatin are increased in IRAP
      patients versus healthy controls. Our data suggest that these adipokines might be
      involved in IRAP pathogenesis and that a possible increased cardiovascular risk
      in these patients, through an early onset atherosclerosis, should be kept in
      mind. SAA might be a link between IRAP and increased cardiovascular diseases.

PMID- 23137678
TI  - Rumination, depressive symptoms and awareness of illness in schizophrenia.
AB  - BACKGROUND: Depressive symptoms are common in schizophrenia. Previous studies
      have observed that depressive symptoms are associated with both insight and
      negative appraisals of illness, suggesting that the way in which the person
      thinks about their illness may influence the occurrence of depressive responses.
      In affective disorders, one of the most well-established cognitive processes
      associated with depressive symptoms is rumination, a pattern of perseverative,
      self-focused negative thinking. AIMS: This study examined whether rumination
      focused on mental illness was predictive of depressive symptoms during the
      subacute phase of schizophrenia. METHOD: Forty participants with a diagnosis of
      schizophrenia and in a stable phase of illness completed measures of rumination,
      depressive symptoms, awareness of illness, and positive and negative symptoms.
      RESULTS: Depressive symptoms were correlated with rumination, including when
      controlling for positive and negative symptoms. The content of rumination
      frequently focused on mental illness and its causes and consequences, in
      particular social disability and disadvantage. Depressive symptoms were predicted
      by awareness of the social consequences of mental illness, an effect that was
      mediated by rumination. CONCLUSIONS: Results suggest that a process of
      perseveratively dwelling upon mental illness and its social consequences may be a
      factor contributing to depressive symptoms in people with chronic schizophrenia.

PMID- 23137679
TI  - The C-value paradox, junk DNA and ENCODE.

PMID- 23137680
TI  - Biodiversity in water and on land.

PMID- 23137681
TI  - Spontaneous innovation in tool manufacture and use in a Goffin's cockatoo.

PMID- 23137682
TI  - The world's rarest whale.

PMID- 23137683
TI  - Behavioral neuroscience: learning to suckle with signature odor.
AB  - A new study in mice reveals that an apparently innate behavior, suckling, is
      triggered not by a classical pheromone but by the pup learning the complex
      signature odor of its mother.

PMID- 23137684
TI  - Evolution: drift will tear us apart.
AB  - That the widely scattered geographical distribution of some animals could be due
      to continental drift is a neat idea. Now, cave animals provide evidence for
      extreme long-term persistence on continents drifting apart.

PMID- 23137685
TI  - Light perception: more than meets the eyes.
AB  - Larval zebrafish lacking eyes and pineal organ show elevated activity levels and
      undirected light-seeking behaviour upon loss of illumination. This behaviour,
      termed dark photokinesis, is mediated by hypothalamic deep brain photoreceptors
      expressing melanopsin.

PMID- 23137686
TI  - Biogeography: are tropical species less specialised?
AB  - Species richness increases from the poles to the tropics, which has led to the
      view that interactions in tropical species are more specialised. A new study on
      pollinators and seed dispersers finds that tropical interactions are in fact less
      specialised.

PMID- 23137687
TI  - Cytokinesis: RhoGEFs control a developmental cleavage switch.
AB  - New findings provide evidence that developmentally staged RhoGEFs control
      assembly of two alternative forms of cleavage furrows: the 'Rappaport' furrows,
      which govern division of Drosophila syncytial cortical division cycles, and
      conventional spindle-directed furrows.

PMID- 23137688
TI  - General anesthesia: activating a sleep switch?
AB  - A widely used general anesthetic directly depolarizes sleep-promoting cells in
      the brain at doses that produce unconsciousness. The activation of an endogenous
      sleep pathway likely plays a role in general anesthesia.

PMID- 23137689
TI  - Plant development: how long is a root?
AB  - The plant hormone cytokinin controls root growth by balancing the division and
      differentiation of stem cells. But what controls accumulation of cytokinin? A new
      study has identified a regulatory loop between a transcription factor, PHABULOSA,
      and cytokinin biosynthesis that creates robust domains of cytokinin activity.

PMID- 23137690
TI  - Social evolution: when promiscuity breeds cooperation.
AB  - In social evolution theory, it has become common wisdom that close family ties
      should promote cooperative behaviour. Yet, in social insects, evidence is
      accumulating that queen promiscuity and low relatedness sometimes work better.

PMID- 23137691
TI  - Strigolactones: destruction-dependent perception?
AB  - Strigolactones control many aspects of plant growth and development, but the
      active form(s) of strigolactones and their mode of action at the molecular level
      are unknown. A new study provides evidence that an alpha/beta-fold protein plays
      a central multifunctional role in strigolactone metabolism, perception and
      signalling.

PMID- 23137692
TI  - Memory formation: traversing the highwire.
AB  - Molecules that suppress memory formation protect against the consolidation of
      inaccurate information. A recent study in Drosophila has identified a new pathway
      for memory suppression and the neurons that are a gateway to long-term memory
      formation.

PMID- 23137693
TI  - Imprinting: DNA methyltransferases illuminate reprogramming.
AB  - Progress in studying epigenetic reprogramming in plants has been impeded by the
      difficulty in obtaining tissue for analysis. Now, using a combination of
      fluorescent reporters and translational fusions, a new study sheds some light on
      this process.

PMID- 23137694
TI  - Study of the effect exerted by fructo-oligosaccharides from yacon (Smallanthus
      sonchifolius) root flour in an intestinal infection model with Salmonella
      Typhimurium.
AB  - Beneficial effects of prebiotics like inulin and fructo-oligosaccharides (FOS)
      have been proven in health and nutrition. Yacon (Smallanthus sonchifolius), an
      Andean crop, contains FOS (50-70% of its dry weight) and, therefore, is
      considered a prebiotic. Commercial FOS can upregulate total secretory IgA (S-IgA)
      in infant mice, prevent infection with Salmonella in swine or enhance immune
      response for Salmonella vaccine in a mouse model. Previously, we found that
      administration of yacon root flour regulates gut microbiota balance and has
      immunomodulatory effects without inflammatory responses. The aim of the present
      paper is to analyse if yacon prevents enteric infection caused by a strain of
      Salmonella enteritidis serovar Typhimurium (S. Typhimurium) in a mouse model.
      BALB/c mice were supplemented with yacon flour (45 d), challenged with S.
      Typhimurium and killed to study pathogen translocation, total and specific IgA
      production by ELISA, presence of IgA and other cytokines and Toll-like receptor 4
      (TLR4) and clustor of differentiation 206 (CD206) receptors positive cells by
      immunofluorescence and histological changes. Yacon flour administration had a
      protective effect from 15 to 30 d of treatment. We found a peak of total S-IgA
      production without translocation of the pathogen for these periods. At 30 d,
      there was an increase in IL-6 and macrophage inflammatory proteins-1ap cells and
      expression of the receptors CD206 and TLR4. Yacon flour did not have incidence in
      pathogen-specific S-IgA production. Longer periods (45 d) of administration had
      no protective effect. Therefore, yacon can prevent enteric infection caused by S.
      Typhimurium when given up to 30 d; this effect would be mediated by enhancing non
      specific immunity, such as total S-IgA, that improves the immunological
      intestinal barrier.

PMID- 23137695
TI  - Performance and characteristics evaluation of a sodium hyaluronate-based
      microneedle patch for a transcutaneous drug delivery system.
AB  - The MicroHyala((r)) microneedle (MN) patch was developed to provide a simple,
      safe, and effective drug delivery system. In this study, we examined the
      performance and characteristics of our fabricated MN patch to identify potential
      quality issues with future commercial application. Mechanical failure force
      analysis identified that the strength of the MN patch was affected by
      environmental humidity, because higher moisture levels weakened the strength of
      the MN. Incorporation of all-trans retinoic acid (ATRA) or ovalbumin (OVA) into
      the MN patch decreased the mechanical failure force by almost 50% of the strength
      of placebo (without drug) patches. ATRA-loaded MN patches displayed good
      stability after storage at 4  degrees C, with more than 90% and 85% of the drug
      remaining in the patch after 8 and 24 weeks of storage, respectively. Tetanus
      toxoid- and diphtheria toxoid-loaded MN patches stored for 12 months induced
      robust antigen-specific immune responses similar to the responses by freshly
      prepared MN patches. Fluorescence imaging findings suggested that prolonged
      antigen deposition was induced by MN-mediated fluorescein isothiocyanate-labeled
      (FITC)-OVA vaccination. Overall, although the strength of MN requires
      improvement, our developed MN patch appears to be an effective pharmaceutical
      product providing a simple, safe, and relatively painless approach.

PMID- 23137696
TI  - Functional MRI and functional connectivity of the visual system of awake pigeons.
AB  - At present, functional MRI (fMRI) is increasingly used in animal research but the
      disadvantage is that the majority of the imaging is applied in anaesthetized
      animals. Only a few articles present results obtained in awake rodents. In this
      study both traditional fMRI and resting state (rsfMRI) were applied to four
      pigeons, that were trained to remain still while being imaged, removing the need
      for anesthesia. This is the first time functional connectivity measurements are
      performed in a non-mammalian species. Since the visual system of pigeons is a
      well-known model for brain asymmetry, the focus of the study was on the neural
      substrate of the visual system. For fMRI a visual stimulus was used and
      functional connectivity measurements were done with the entopallium (E; analog
      for the primary visual cortex) as a seed region. Interestingly in awake pigeons
      the left E was significantly functionally connected to the right E. Moreover we
      compared connectivity maps for a seed region in both hemispheres resulting in a
      stronger bilateral connectivity starting from left E then from right E. These
      results could be used as a starting point for further imaging studies in awake
      birds and also provide a new window into the analysis of hemispheric dominance in
      the pigeon.

PMID- 23137697
TI  - Early deficits in declarative and procedural memory dependent behavioral function
      in a transgenic rat model of Huntington's disease.
AB  - In Huntington's disease (HD) cognitive deficits co-exist with motor impairments,
      both contributing to the overall disease symptomology. Despite short-term and
      working memory impairments, learning and other non-motoric behavioral deficits
      arising from the damage to frontostriatal loop being common in HD patients, most
      of the experimental work with transgenic animals focuses on motor symptoms. The
      transgenic rat model (tgHD) recapitulates many hallmark HD-like symptoms, such as
      huntingtin aggregates, cellular loss and dysfunction, and motor, and some
      cognitive deficits. In the current study we tested tgHD rats in two different
      cognitive, water maze competition paradigms to learn more about the impact of the
      transgene on learning and memory processing using hippocampal- and striatal-based
      memory systems. The tgHD rats had early and robust cognitive deficits in learning
      and memory function in both paradigms. Specifically, the transgenic animals were
      impaired in task acquisition and committed more procedural errors with the
      strongest phenotype amongst the homozygote tgHD. Although the transgenic animals
      were capable of using both procedural and declarative memory, their response
      patterns were distinct from wild-type animals. Wide spread huntingtin aggregates
      were observed at 13 months, but neither PET nor autoradiography indicated
      neuronal loss or dysfunction in striatal dopamine receptor population. In
      summary, the homozygote tgHD showed a robust learning and memory impairment prior
      to any clear motor deficits, or striatal dysfunction. However, the data were not
      conclusive regarding how the memory systems were compromised and the precise
      nature and underlying mechanism of the cognitive deficit in the tgHD model
      requires further investigation.

PMID- 23137698
TI  - Effects of sodium butyrate on methamphetamine-sensitized locomotor activity.
AB  - Neuroadaptations associated with behavioral sensitization induced by repeated
      exposure to methamphetamine (MA) appear to be involved in compulsive drug pursuit
      and use. Increased histone acetylation, an epigenetic effect resulting in altered
      gene expression, may promote sensitized responses to psychostimulants. The role
      of histone acetylation in the expression and acquisition of MA-induced locomotor
      sensitization was examined by measuring the effect of histone deacetylase
      inhibition by sodium butyrate (NaB). For the effect on expression, mice were
      treated repeatedly with MA (10 days of 2mg/kg MA) or saline (10 days), and then
      vehicle or NaB (630 mg/kg, intraperitoneally) was administered 30 min prior to MA
      challenge and locomotor response was measured. NaB treatment increased the
      locomotor response to MA in both acutely MA treated and sensitized animals. For
      acquisition, NaB was administered 30 min prior to each MA exposure (10 days of 1
      or 2mg/kg), but not prior to the MA challenge test. Treatment with NaB during the
      sensitization acquisition period significantly increased locomotor activation by
      MA in sensitized mice only. NaB alone did not significantly alter locomotor
      activity. Acute NaB or MA, but not the combination, increased striatal
      acetylation at histone H4. Repeated treatment with MA, but not NaB or MA plus
      NaB, increased striatal acetylation at histone H3. Although increased histone
      acetylation may alter the expression of genes involved in acute locomotor
      response to MA and in the acquisition of MA-induced sensitization, results for
      acetylation at H3 and H4 showed little correspondence with behavior.

PMID- 23137700
TI  - Hearing safety of long-term treatment with theta burst stimulation.
AB  - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) for the
      experimental treatment of tinnitus or auditory hallucinations aims at a
      modulation of cortical activity in areas of auditory perception and processing.
      Continuous theta burst stimulation (cTBS) is a patterned rTMS paradigm with lower
      stimulation intensity and shorter stimulus duration that is increasingly used for
      the optimization of rTMS-treatment paradigms. Possible interference with
      physiological brain function and the noise emitted by the rTMS device might
      induce relevant unwanted impairment of hearing and speech perception.
      OBJECTIVE/HYPOTHESIS: Here, we investigate the audiological safety of long-term,
      bilateral cTBS for the treatment of auditory phantom perception. METHODS: Forty
      eight patients with chronic tinnitus were treated for four weeks with bilateral
      continuous theta burst stimulation to the temporal (n = 16), temporoparietal (n =
      16) or a non-cortical control (n = 16) site. Measurements in these patients were
      obtained before and four weeks after treatment. The rTMS-induced noise was
      measured at various frequency levels. RESULTS: No evidence was found for auditory
      threshold shifts or alterations in the perception of speech in quiet or in
      background noise by bilateral, long-term theta burst stimulation to the temporal
      or temporoparietal cortex with a loudness of up to 84 dB SPL (A). CONCLUSIONS:
      Theta burst stimulation of the temporal and temporoparietal cortex appears to be
      safe with respect to hearing and speech perception. These data provide evidence
      for the audiological safety of rTMS in the experimental treatment of auditory
      phantom perception.

PMID- 23137701
TI  - Eyelid myokymia in an older subject after repetitive sessions of anodal
      transcranial direct current stimulation.

PMID- 23137699
TI  - Working memory for temporal order is impaired after selective neonatal
      hippocampal lesions in adult rhesus macaques.
AB  - A previous study in this laboratory demonstrated, for the first time, that
      neonatal lesions of the hippocampus impair monitoring working memory, as measured
      by a self-order task, but spare recency memory, as measured by the session-unique
      delayed nonmatching task. To substantiate and extend this novel finding, we
      assessed working memory in these same animals using a serial order memory task.
      In humans and non-human primates the serial order memory task has been shown to
      be dependent upon the integrity of the dorsolateral prefrontal cortex.
      Additionally, the serial order task has the ability to examine the integrity of
      non-dorsolateral dependent working memory functions, providing specificity to
      conclusions drawn from this task. Thus, monkeys with neonatal lesions of the
      hippocampus and sham-operated control subjects were tested on two versions of the
      serial order memory task (3 and 4 objects). The results of this study
      demonstrated that neonatal hippocampal lesions did not impair performance on the
      3-object version of the task, confirming our previous finding of intact non-dlPFC
      dependent working memory. In contrast, these same animals showed a significant
      impairment on the dlPFC dependent phase of the 4-object serial order task. This
      finding was further confirmed through a series of probe trials. These results, in
      combination with our earlier finding, suggest that early lesions of the
      hippocampus may have impacted the function of the dlPFC or its interactions with
      the hippocampus.

PMID- 23137702
TI  - Transcranial direct current stimulation (tDCS) enhances reconsolidation of long
      term memory.
AB  - A new and weak memory trace undergoes consolidation to gain resistance against
      interfering stimuli. When an encoded memory is recalled, it becomes labile and
      another round of consolidation, or reconsolidation, is required to restore its
      stability. Transcranial direct current stimulation (tDCS) is a non-invasive
      method of altering cortical excitability. The aim of this study was to examine
      the effects of tDCS on the reconsolidation of long-term verbal memory.
      Participants (n = 15) memorized words in the encoding session, then reactivated
      the memory of the words 3 h later using an old-new recognition task under anodal,
      cathodal and sham stimulation to the left dorsolateral prefrontal cortex (DLPFC).
      Finally, after another 5 h, they performed another round of the old-new
      recognition task and rated their confidence. Anodal tDCS during the second
      session resulted in significantly more words recognized in the third session as
      compared to cathodal and sham stimulation. Cathodal tDCS did not affect the
      recognition performance compared to sham stimulation. These results cannot be
      attributed to differences in response times and confidence ratings, as they were
      comparable in all conditions. In order to study whether the activation of a
      memory was crucial for the enhancing effects of anodal tDCS, a group of controls
      (n = 15) did not perform the recognition task in the second session but still
      underwent stimulation. Contrary to the main group, anodal stimulation did not
      enhance the memory performance for the control group. This result suggests that
      anodal tDCS over the left DLPFC can enhance the reconsolidation of long-term
      memory only when the memory has been reactivated. 

PMID- 23137703
TI  - Experimental study of the course of threshold current, voltage and electrode
      impedance during stepwise stimulation from the skin surface to the human cortex.
AB  - BACKGROUND: Transcranial electric stimulation as used during intraoperative
      neurostimulation is dependent on electrode and skull impedances. OBJECTIVE:
      Threshold currents, voltages and electrode impedances were evaluated with
      electrical stimulation at 8 successive layers between the skin and the cerebral
      cortex. PATIENTS AND METHODS: Data of 10 patients (6f, 53 +/- 11 years) were
      analyzed. Motor evoked potentials were elicited by constant current stimulation
      with corkscrew type electrodes (CS) at C3 and C4 in line with standard
      transcranial electric stimulation. A monopolar anodal ball tip shaped probe was
      used for all other measurements being performed at the level of the skin, dura
      and cortex, as well as within the skull by stepwise performed burr holes close to
      C3 resp. C4. RESULTS: Average stimulation intensity, corresponding voltage and
      impedance for muscle MEPs at current motor threshold (CMT) were recorded: CS 54
      +/- 23 mA (mean +/- SD), 38 +/- 21 V, 686 +/- 146 Omega; with the monopolar probe
      on skin 55 +/- 28 mA, 100 +/- 44 V, 1911 +/- 683 Omega and scalp 59 +/- 32 mA, 56
      +/- 28 V, 1010 +/- 402 Omega; within the skull bone: outer compact layer 33 +/-
      23 mA, 91 +/- 53 V, 3734 +/- 2793 Omega; spongiform layer 33 +/- 23 mA, 70 +/- 44
      V, 2347 +/- 1327 Omega; inner compact layer (ICL) 28 +/- 19 mA, 48 +/- 23 V, 2103
      +/- 1498 Omega; on dura 25 +/- 12 mA, 17 +/- 12 V, 643 +/- 244 Omega and cortex
      14 +/- 6 mA, 11 +/- 5 V, 859 +/- 300 Omega. CMTs were only significantly
      different for CS (P = 0.02) and for the monopolar probe between the cortex and
      ICL (P = 0.03), scalp (P = 0.01) or skin (P = 0.01) and between ICL and CS (P <=
      0.01) or skin (P <= 0.01). CONCLUSION: The mean stimulation current of the CMT
      along the extracranial to intracranial anodal trajectory followed a stepwise
      reduction. VMT was strongly dependent on electrode impedance. CMT within the
      skull layers was noted to have relative strong shunting currents in scalp layers.

PMID- 23137704
TI  - PTEN/MAPK pathways play a key role in platelet-activating factor-induced
      experimental pulmonary tumor metastasis.
AB  - In this study, we investigated the role of PTEN (phosphatase and tensin homolog
      deleted on chromosome 10) in a platelet-activating factor (PAF)-induced
      experimental pulmonary tumor metastasis model. An adenovirus carrying PTEN cDNA
      (Ad-PTEN) reversed PAF-induced increase in phosphorylation of AKT as well as
      pulmonary metastasis of B16F10. PAF-induced pulmonary metastasis was inhibited by
      MAPK inhibitors, but not by PI3K inhibitor. Ad-PTEN abrogated PAF-induced
      phosphorylation of MAPKs. These data indicate PTEN/MAPK pathways play a key role
      in PAF-induced tumor metastasis.

PMID- 23137705
TI  - Anticoagulant properties of the anti-inflammatory cytokine IL-10 in a factor Xa
      activated human monocyte model.
AB  - BACKGROUND: Monocytes and factor Xa (FXa) are procoagulant agents implicated in
      the physiopathological processes of atherosclerosis and thrombosis. OBJECTIVE: we
      evaluated the anticoagulant effect of the anti-inflammatory cytokine IL-10 on an
      FXa-activated human monocyte (Hu-monocyte) procoagulant phenotype. METHODS: Hu
      monocytes were purified by elutriation and activated by FXa. The effect of IL-10
      was assessed by means of a 2 h pre-incubation step with recombined human IL-10
      (0.5 and 1 ng/mL). Real-time RT-PCR and Western blotting were used to evaluate
      the effect of IL-10 on tissue factor (TF) mRNA and protein synthesis. A thrombin
      generation (TG) assay was used as a functional test to assess the effect of IL-10
      on TF-dependent TG. RESULTS: we showed that IL-10 inhibited both TFmRNA and TF
      protein expression in a dose-dependant manner.We showed, as a functional
      consequence, that IL-10 inhibited Hu-monocyte-triggered TG and that this
      inhibition was concentration-dependant, and significant for all TG phases. The
      rate index of the propagation phase (rate index) was the most sensitive parameter
      while the endpoint of TG decay (S-tail) and the endogenous thrombin potential
      (ETP) were the least sensitive (inhibition of 80, 40 and 30% respectively). The
      IL-10 pattern of TG inhibition was similar to TF-Ab-induced inhibition: IC(50)
      were not reached by ETP and S-tail, and the lowest IC(50) values were reached by
      the rate index (0.61 +/- 0.12 ng/mL and 1.87 +/- 0.35 MUg/mL respectively).
      CONCLUSION: the anticoagulant effect of the anti-inflammatory cytokine IL-10 in
      an FXa-activated Hu-monocyte model is an additional illustration of the cross
      talk between inflammation and coagulation, opening new approaches in the field of
      arteriosclerosis and thrombosis.

PMID- 23137707
TI  - Response to letter to the editor - implementation of integrative approaches to
      improve the design of Crohn's disease clinical trials.

PMID- 23137706
TI  - Does undernutrition still prevail among nursing home residents?
AB  - BACKGROUND & AIMS: During recent years public awareness about malnutrition has
      increased and collective initiatives have been undertaken. Simultaneously, the
      number of older adults is increasing, and the elderly care has been placed under
      pressure. The aim was to assess the nutritional situation and one-year mortality
      among nursing home (NH) residents, and compare with historical data. METHODS:
      Mini Nutritional Assessment-Short Form (MNA-SF), ADL Barthel Index (BI), Short
      Portable Mental Status Questionnaire (SPMSQ), EQ-5D, Charlson Comorbidity Index
      (CCI), and blood samples were collected from 172 NH residents (86.3 +/- 8 years,
      70% women). Mortality data was taken from NH records. Nutritional data from 166
      NH residents (83.8 +/- 8 years, 61% women) examined in 1996 was retrieved for
      historical comparison. RESULTS: The prevalence of malnutrition was 30%, as
      compared to 71% in the historical data set, corresponding to a present average
      body mass index of 23.7 +/- 5.1 compared with 22.3 +/- 4.2 kg/m(2) (p < 0.01).
      Reduced nutritional status was associated with decline in function (p < 0.001)
      and cognition (p < 0.01). One-year mortality was 24%. Regression analyses
      indicated high age (OR = 1.09, 95% CI (1.03-1.16)), high scores in CCI (OR =
      1.54, (1.19-1.99)), low BMI (OR = 2.47, (1.14-5.38)) and malnutrition (OR = 2.37,
      (1.07-5.26)) to be independently associated with one-year mortality. CONCLUSIONS:
      Malnutrition still prevails and is associated with deteriorated cognition,
      function and increased mortality. A possible improvement in nutritional status in
      NH residents over time was observed.

PMID- 23137708
TI  - Evidence for the fusion of extracellular vesicles with/without DNA to form
      specific structures in fertilized chicken eggs, mice and rats.
AB  - With a combination of cultivation and phase-contrast and fluorescence microscopic
      observation, we first found that fusion of extracellular vesicles with or without
      membranes occurred in fertilized chicken eggs. In order to find solid evidence
      for fusion, we collected many fusion data from various tissues; primo vessels and
      pancreases of mice and pancreases and omentums of rats. Especially, by using
      acridine orange vital staining to demonstrate DNA and phase-contrast and
      fluorescence microscopy for long real-time observation, we found that many of the
      extracellular vesicles involved in the fusion process contained DNAs. The fusions
      fall into two main patterns: pattern A characterizes a fusion of less agitated
      extracellular vesicles without membranes. Pattern B is a fusion of vigorously
      vibrating extracellular vesicles in a certain membrane. Considering all data,
      tables, pictures and movies, we were able to show fusions of DNA extracellular
      vesicles without or with membranes in several tissues of three species.
      Interestingly, some of the fused structures share the same morphology as normal
      cell's in terms of overall shape, size and DNA signals in the center. Thus, in
      this article we first report the evidence for the fusion of extracellular
      vesicles with/without DNA toward a specific structure and discuss our findings by
      comparing with those of other pioneer's works in search for a mitosis-free
      alternative pathway for generating new cells.

PMID- 23137709
TI  - Meat science: From proteomics to integrated omics towards system biology.
AB  - Since the main ultimate goal of farm animal raising is the production of proteins
      for human consumption, research tools to investigate proteins play a major role
      in farm animal and meat science. Indeed, proteomics has been applied to the field
      of farm animal science to monitor in vivo performances of livestock animals
      (growth performances, fertility, milk quality etc.), but also to further our
      understanding of the molecular processes at the basis of meat quality, which are
      largely dependent on the post mortem biochemistry of the muscle, often in a
      species-specific way. Post mortem alterations to the muscle proteome reflect the
      biological complexity of the process of "muscle to meat conversion," a process
      that, despite decades of advancements, is all but fully understood. This is
      mainly due to the enormous amounts of variables affecting meat tenderness per se,
      including biological factors, such as animal species, breed specific
      characteristic, muscle under investigation. However, it is rapidly emerging that
      the tender meat phenotype is not only tied to genetics (livestock breeding
      selection), but also to extrinsic factors, such as the rearing environment,
      feeding conditions, physical activity, administration of hormonal growth
      promotants, pre-slaughter handling and stress, post mortem handling. From this
      intricate scenario, biochemical approaches and systems-wide integrated
      investigations (metabolomics, transcriptomics, interactomics, phosphoproteomics,
      mathematical modeling), which have emerged as complementary tools to proteomics,
      have helped establishing a few milestones in our understanding of the events
      leading from muscle to meat conversion. The growing integration of omics
      disciplines in the field of systems biology will soon contribute to take further
      steps forward.

PMID- 23137710
TI  - Predicting contraceptive use from an egalitarian model of women's overall
      household power vis-a-vis conventional power models and third variables.
AB  - Research on gender power in contraceptive use has focused on whether women have
      an active role in household decision-making (the participation model) or on the
      extent of their control of domestic decisions (the control model); it has also
      addressed the joint effects of power, age, education and work. Findings published
      in this journal (Woldemicael, 2009) suggest a third power model according to
      which wives make joint decisions with their husbands on important domestic areas
      and autonomous decisions on secondary matters (the egalitarian model). In
      analyses of Demographic and Health Survey data sets from 46 countries, the
      egalitarian model explained contraceptive use better than the control and
      participation models in 19 out of 20 countries outside sub-Saharan Africa; its
      superiority was less overwhelming in this sub-continent. Power effects on
      contraceptive use that depend on women's education, age and work for cash are
      larger in sub-Saharan Africa than in other world regions, whereas independent
      power effects differ little regionally, suggesting the action of a personality
      factor. Situational specification of decision importance and direct measurement
      of women's assertiveness are needed to improve the explanation of contraceptive
      behaviour.

PMID- 23137711
TI  - Protein and lipid damage in maple syrup urine disease patients: l-carnitine
      effect.
AB  - Maple syrup urine disease (MSUD) is an inborn error of metabolism biochemically
      characterized by elevated levels of the branched chain amino acids (BCAA)
      leucine, isoleucine, valine and the corresponding branched-chain alpha-keto
      acids. This disorder is clinically characterized by ketoacidosis, seizures, coma,
      psychomotor delay and mental retardation whose pathophysiology is not completely
      understood. Recent studies have shown that oxidative stress may be involved in
      neuropathology of MSUD. l-Carnitine (l-Car) plays a central role in the cellular
      energy metabolism because it transports long-chain fatty acids for oxidation and
      ATP generation. In recent years many studies have demonstrated the antioxidant
      role of this compound. In this work, we investigated the effect of BCAA
      restricted diet supplemented or not with l-Car on lipid peroxidation and in
      protein oxidation in MSUD patients. We found a significant increase of
      malondialdehyde and of carbonyl content in plasma of MSUD patients under BCAA
      restricted diet compared to controls. Furthermore, patients under BCAA-restricted
      diet plus l-Car supplementation presented a marked reduction of malondialdehyde
      content in relation to controls, reducing the lipid peroxidation. In addition,
      free l-Car concentrations were negatively correlated with malondialdehyde levels.
      Our data show that l-Car may have an antioxidant effect, protecting against the
      lipid peroxidation and this could represent an additional therapeutic approach to
      the patients affected by MSUD.

PMID- 23137713
TI  - Drug reaction with eosinophilia and systemic symptoms caused by lenalidomide.

PMID- 23137714
TI  - Thyroid function tests at delivery and risk for postpartum depressive symptoms.
AB  - Postpartum depression (PPD) is a common childbirth complication, which can have
      negative effects on both the newly delivered woman and her family. This condition
      is underdiagnosed and inadequately treated, while a biological diagnostic test is
      not yet available. Furthermore, postpartum thyroid dysfunction is common among
      new mothers, and some evidence point to an association between PPD and thyroid
      function disturbances. The aim of this study was to evaluate the possible
      association between serum levels of thyroid hormones at the time of delivery, and
      the later development of depressive symptoms, using data from a population based
      cohort of Swedish women. Blood samples were collected during delivery from 347
      participating women, delivering at Uppsala University Hospital. The participating
      women filled in at least one of three structured questionnaires, containing the
      Edinburgh Postnatal Depression Scale (EPDS), at five days, six weeks and six
      months postpartum. A cut-off of 12 or more was applied on the EPDS, to identify
      cases of self-reported PPD and controls. Using a binary logistic regression model
      (adjusting for previous psychiatric contact, smoking during pregnancy, pre
      pregnancy body mass index (BMI) and sleep), having a thyroid stimulating hormone
      (TSH) level over the clinical cut-off level of 4.0 mU/L was associated with
      increased risk for depressive symptoms at six months postpartum (OR 11.30, 95% CI
      1.93-66.11). A ROC analysis revealed that the predictive variable (PV) had
      significant predictive ability for PPD at 6 months postpartum, given that the AUC
      was 0.764, and at a PV cut-off value of 6.33, the sensitivity and specificity
      were 76.2% and 69.4%, respectively. If these findings are replicated in future
      studies, they can have important clinical implications, since TSH determination
      is an inexpensive routine blood test, and its inclusion in a biological screening
      test for PPD involving other parameters would be tempting.

PMID- 23137712
TI  - Treatment of lung infection in patients with cystic fibrosis: current and future
      strategies.
AB  - In patients with cystic fibrosis (CF) lung damage secondary to chronic infection
      is the main cause of death. Treatment of lung disease to reduce the impact of
      infection, inflammation and subsequent lung injury is therefore of major
      importance. Here we discuss the present status of antibiotic therapy for the
      major pathogens in CF airways, including prophylaxis against infection,
      eradication of early infection, suppression of chronic infection, and the
      treatment of infective exacerbations. We outline measures to optimize maintenance
      treatment for infection in the light of novel antibiotic drug formulations. We
      discuss new developments in culture-independent microbiological diagnostic
      techniques and the use of tools for monitoring the success of antibiotic
      treatment courses. Finally, cost-effectiveness analyses for antibiotic treatment
      in CF patients are discussed.

PMID- 23137715
TI  - Aberrant stress hormone receptor balance in the human prefrontal cortex and
      hypothalamic paraventricular nucleus of depressed patients.
AB  - The prefrontal cortex (PFC) plays an important role in the regulation of the
      hypothalamo-pituitary-adrenal (HPA)-axis regarding stress response and possibly
      also depression. We used quantitative real-time PCR to determine the mRNA levels
      of 17 stress-related genes in the human postmortem anterior cingulate cortex
      (ACC) and dorsolateral PFC (DLPFC) of patients with mood disorder and of well
      matched controls. The correlation between the expression of these DLPFC genes and
      their earlier measured expression in the paraventricular nucleus (PVN) of the
      same subjects was also determined. Transcript level of mineralocorticoid receptor
      (MR) was significantly decreased, while the ratio of glucocorticoid receptor (GR)
      alpha to MR mRNA level was increased in the ACC/DLPFC, both in the bipolar and
      major depressive disorder subgroups and also in the pooled depression group.
      Significantly inverse correlations were found for MR mRNA level and for
      GRalpha/MR ratio between the DLPFC and PVN. A selective disturbance of MR and of
      the GRalpha/MR ratio thus seems to exist in the ACC/DLPFC in depression, which
      was inversely correlated with the corresponding levels in the PVN. These changes
      may contribute to HPA-axis hyperactivity and hence to depression etiology.

PMID- 23137717
TI  - Practical algorithms for managing common gastrointestinal symptoms in infants.
AB  - OBJECTIVE: In early infancy, various gastrointestinal symptoms (e.g.,
      constipation, regurgitation, crying/fussiness, infantile colic, and excessive
      gas) are common problems and may result in numerous visits to pediatricians.
      Worldwide, this often results in switching infant formulas because parents (and
      sometimes doctors) believe these symptoms reflect a formula intolerance. However,
      in many cases, these infants are growing and developing normally. This study was
      performed to offer family pediatricians consensus-based algorithms on the
      management of the most common gastrointestinal symptoms in infants. METHODS: A
      group of pediatric gastroenterologists and pediatric allergists from Europe, USA,
      Latin America, and Asia developed guidelines and practical algorithms to assist
      general pediatricians in addressing this challenge. RESULTS: Five such practice
      recommendations were developed after a thorough literature review. These
      algorithms should not be considered as an "evidence-based guideline"; on the
      contrary, the authors are convinced that challenging these proposals will result
      in updated and improved versions. CONCLUSION: To date, these algorithms, based on
      the published literature, are the result of a broad consensus of pediatric
      gastroenterologists from different continents.

PMID- 23137716
TI  - Structure of the Trypanosoma cruzi protein tyrosine phosphatase TcPTP1, a
      potential therapeutic target for Chagas' disease.
AB  - Chagas' disease, a neglected tropical affliction transmitted by the flagellated
      protozoan Trypanosoma cruzi, is prevalent in Latin America and affects nearly 18
      million people worldwide, yet few approved drugs are available to treat the
      disease. Moreover, the currently available drugs exhibit severe toxicity or are
      poorly effective in the chronic phase of the disease. This limitation, along with
      the large population at risk, underscores the urgent need to discover new
      molecular targets and novel therapeutic agents. Recently, the T. cruzi protein
      tyrosine phosphatase TcPTP1 has been implicated in the cellular differentiation
      and infectivity of the parasite and is therefore a promising target for the
      design of novel anti-parasitic drugs. Here, we report the X-ray crystal structure
      of TcPTP1 refined to a resolution of 2.18 A, which provides structural insights
      into the active site environment that can be used to initiate structure-based
      drug design efforts to develop specific TcPTP1 inhibitors. Potential strategies
      to develop such inhibitors are also discussed.

PMID- 23137718
TI  - Body-related behaviours and cognitions in the eating disorders.
AB  - BACKGROUND: Different body-related behaviours and cognitions (checking,
      avoidance, comparison, display) have been shown to be related to unhealthy eating
      attitudes in a non-clinical sample. AIMS: This study tested whether the use of
      body-related behaviours is higher in eating-disordered women than in non-clinical
      women. It also examined whether the use of body-related behaviours is associated
      with psychological characteristics (particularly anxiety, depression and
      narcissistic characteristics), controlling for age and eating pathology. METHOD:
      Ninety-nine adult women with diagnosed eating disorders (mean age = 30.4 years,
      SD = 9.44; mean body mass index = 21.9, SD = 6.39) completed standardized
      measures of eating pathology, anxiety and depression, narcissistic
      characteristics, and body-related behaviours and cognitions. RESULTS: The Body
      Related Behaviours Scale (BRBS) had acceptable levels of internal consistency in
      this group, and its scales were only weakly to moderately correlated with each
      other. There were no differences between diagnostic groups, but the clinical
      group had higher scores that a previous non-clinical sample on three of the
      scales. The four body-related behaviours had different patterns of association
      with eating pathology, depression and narcissistic features. However, anxiety was
      not associated with BRBS scores. CONCLUSIONS: The findings support the importance
      of a wide range of body-related behaviours and cognitions in understanding the
      eating disorders. However, the lack of an association with anxiety is counter to
      the suggestion that the various behaviours measured by the BRBS reflect safety
      behaviours on the part of sufferers. Depression and narcissistic features might
      be more important in maintaining such behaviours.

PMID- 23137719
TI  - The absolute monocyte and lymphocyte prognostic index for patients with diffuse
      large B-cell lymphoma who receive R-CHOP.
AB  - BACKGROUND: The baseline absolute monocyte count and absolute lymphocyte count
      were used to generate a prognostic index (the AMLPI) for survival in diffuse
      large B-cell lymphoma (DLBCL). METHODS: Data from 245 patients with DLBCL who
      were treated with standard R-CHOP (rituximab, cyclophosphamide, doxorubicin
      hydrochloride, vincristine sulfate, prednisone) were reviewed. By using the
      values previously reported for the AMLPI, its prognostic value was examined in
      our population. RESULTS: After a median follow-up of 22 months for censored
      observations, the 3-year progression-free survival (PFS) rates for the
      international prognostic index (IPI) 0-2 and 3-5 risk groups were 73% and 58%,
      respectively (P = .0004); comparable overall survival (OS) rates were 88% and
      68%, respectively (P < .0001). For patients with IPI scores of 0-2, 1-year PFS
      rates for AMLPI low-, intermediate-, and high-risk groups were 92%, 89%, and 80%,
      respectively (P = .022); comparable 1-year OS rates were 96%, 95%, and 80%,
      respectively (P = .049). By multivariate analysis, with the adjustment of IPI in
      the model, AMLPI effects (low- vs. high-risk groups) on PFS and OS rates were
      significant, with P = .046 (hazard ratio [HR] 0.402 [95% CI, 0.164-0.986] and P =
      .052 (HR 0.325 [95% CI, 0.104-1.011]), respectively. CONCLUSIONS: The absolute
      monocyte and lymphocyte counts prognostic index (the AMLPI) may add prognostic
      value beyond that of the IPI for patients with DLBCL who receive R-CHOP.

PMID- 23137720
TI  - Clinical prognostic factors for survival and risk of progression to acute myeloid
      leukemia in patients with myelodysplastic syndromes with < 10% marrow blasts and
      non-unfavorable cytogenetic categories.
AB  - Prognosis of myelodysplastic syndromes (MDS) is an area of ongoing interest.
      Identification of patients with poor outcome in the categories of lower risk
      disease is critical. In this study, we classify a cohort of 332 lower risk MDS
      into 3 groups with differences in survival and risk for leukemic progression that
      could drive treatment approaches to improve prognosis in a fraction of these
      patients. BACKGROUND: Prognosis of MDS and particularly in patients categorized
      as lower risk (< 10% blasts or low and intermediate-1 International Prognostic
      Scoring System [IPSS]) is very heterogeneous and includes patients with very
      different outcomes with current scoring systems. Recently, a new cytogenetic
      classification has been proposed for the revised IPSS in predicting the outcome
      for MDS. PATIENTS AND METHODS: To evaluate the prognostic significance of
      multiple variables for survival and risk of progression to acute myeloid
      leukemia, we analyzed baseline characteristics of 332 lower risk MDS patients
      within the lower risk cytogenetic categories by IPSS and the recent proposal for
      the new cytogenetic classification. RESULTS: In multivariate analysis, severity
      of cytopenias, age > 60 years, bone marrow blasts (5%-9%) and transfusion
      dependency significantly influenced outcome. The combination of these variables
      allowed development of a model which categorizes patients in 3 different groups
      with median survival of 95, 44, and 13 months for groups 1, 2, and 3,
      respectively (P < .001). In addition, this score also stratified patients for
      their risk for leukemic progression, estimated at 2 years in 3.1%, 7.6%, and
      21.3% for each group (P = .024). CONCLUSION: Although karyotype remains the main
      prognostic factor in MDS, the current study identifies clinical parameters
      predicting outcome among patients with the better cytogenetic profile. Degree of
      cytopenias, blasts 5%-9% and transfusion dependence might identify a subset of
      patients within the nonadverse karyotype, in which early or more aggressive
      approaches could possibly be required to improve survival or prevent disease
      progression.

PMID- 23137721
TI  - Hormone and immune system interactions in demyelinating disease.
AB  - The immune, endocrine and nervous systems communicate with each other through a
      myriad of molecules including cytokines, hormones and neurotransmitters.
      Alterations in the balance of the products of these systems affect susceptibility
      to autoimmune disease and also the progression of disease. One of the most
      intensely studied autoimmune diseases is multiple sclerosis (MS). The purpose of
      this review is to explore the relationships between sex hormones and MS disease
      progression and to attempt to understand the paradox that although women are more
      likely to develop MS, female sex hormones appear to be beneficial in symptom
      amelioration. The proposed mechanisms of the therapeutic action of estrogens will
      be discussed with respect to T cell polarization and also on CNS cell
      populations. Investigations into the pathogenesis of multiple sclerosis (MS) and
      animal models of MS have given insights into the interactions between the
      neuroendocrine systems and provide important potential therapeutic venues that
      may be expanded to other autoimmune and neurodegenerative conditions.

PMID- 23137722
TI  - Is the association of self-reported childhood maltreatments and adult
      fibromyalgia syndrome attributable to depression? A case control study.
AB  - OBJECTIVES: Systematic reviews of case-control studies demonstrated an
      association between self-reported childhood sexual and physical abuse and
      fibromyalgia syndrome (FMS). We tested in a case-control study if the association
      of self-reported childhood maltreatments in childhood and in adult FMS-patients
      is attributable to depression. METHODS: All consecutive patients diagnosed with
      FMS of two clinical centres were included into the study from January to June
      2011. Randomly selected age- and sex-matched controls from a representative
      survey of the general German population were used as controls. Childhood
      maltreatments were assessed by the German version of the Childhood Trauma
      Questionnaire CTQ and depression by the two-item depression scale of the German
      version of the Patient Health Questionnaire PHQ-4. The scores of the five CTQ
      subscales were compared between FMS-patients and controls using analysis of
      covariance adjusting for depressed mood. RESULTS: 153 FMS-patients (87.6% women;
      mean age 50.3 years) and 153 age- and sex matched participants of the general
      population were included. The comparison between FMS-patients and population
      controls, adjusted for depressed mood, demonstrated a significant group
      difference for emotional (p<0.001), and sexual abuse (p=0.01). Depressed mood
      fully accounted for group difference in physical abuse (p=0.01) and in emotional
      neglect (p<0.001). Depressed mood partially accounted for group difference in
      emotional abuse (p<0.001), but did not account for group difference in sexual
      abuse (p=0.10). CONCLUSIONS: Reports of FMS-patients some on childhood
      maltreatments were biased by depressed mood. However, the difference in self
      reported childhood sexual abuse between adult FMS-patients and population
      controls was not attributable to depression.

PMID- 23137723
TI  - Association between early attention-deficit/hyperactivity symptoms and current
      verbal and visuo-spatial short-term memory.
AB  - Deficits in short-term memory are common in adolescents with attention
      deficit/hyperactivity disorder (ADHD), but their current ADHD symptoms cannot
      well predict their short-term performance. Taking a developmental perspective, we
      wanted to clarify the association between ADHD symptoms at early childhood and
      short-term memory in late childhood and adolescence. The participants included
      401 patients with a clinical diagnosis of DSM-IV ADHD, 213 siblings, and 176
      unaffected controls aged 8-17 years (mean age, 12.02 +/- 2.24). All participants
      and their mothers were interviewed using the Chinese Kiddie Epidemiologic version
      of the Schedule for Affective Disorders and Schizophrenia to obtain information
      about ADHD symptoms and other psychiatric disorders retrospectively, at an
      earlier age first, then currently. The participants were assessed with the
      Wechsler Intelligence Scale for Children--3rd edition, including Digit Span, and
      the Spatial working memory task of the Cambridge Neuropsychological Test
      Automated Battery. Multi-level regression models were used for data analysis.
      Although crude analyses revealed that inattention, hyperactivity, and impulsivity
      symptoms significantly predicted deficits in short-term memory, only inattention
      symptoms had significant effects (all p<0.001) in a model that included all three
      ADHD symptoms. After further controlling for comorbidity, age of assessment,
      treatment with methylphenidate, and Full-scale IQ, the severity of childhood
      inattention symptoms was still significantly associated with worse verbal (p =
      0.008) and spatial (p ranging from 0.017 to 0.002) short-term memory at the
      current assessment. Therefore, our findings suggest that earlier inattention
      symptoms are associated with impaired verbal and visuo-spatial short-term memory
      at a later development stage. Impaired short-term memory in adolescence can be
      detected earlier by screening for the severity of inattention in childhood.

PMID- 23137724
TI  - Triterpenoid saponins from the aerial parts of Solidago virgaurea alpestris with
      inhibiting activity of Candida albicans yeast-hyphal conversion.
AB  - As part of research for treatments to combat oral dryness, our evaluation of the
      activity of an aqueous extract of Solidago virgaurea (L.) ssp. alpestris
      (Asteraceae) revealed activity against Candida albicans hyphae, the pathogenic
      form of this yeast. Systematic bioassay-guided fractionation of this extract gave
      an active saponin-containing fraction from which six oleanane-type triterpenoid
      saponins were isolated. Three of these were isolated for the first time, as 3-O
      (beta-D-glucopyranosyl-(1->3)-beta-D-glucopyranosyl)-28-O-(beta-D-fucopyranosyl
      (1->2)-alpha-L-rhamnopyranosyl-(1->3)-beta-D-xylopyranosyl-(1->4)-alpha-L
      rhamnopyranosyl-(1->2)-beta-D-xylopyranosyl)-polygalacic acid (virgaureasaponin
      4), 3-O-(beta-D-glucopyranosyl)-28-O-(beta-D-fucopyranosyl-(1->2)-alpha-L
      rhamnopyranosyl-(1->3)-beta-D-xylopyranosyl-(1->4)-alpha-L-rhamnopyranosyl-(1->2)
      beta-D-xylopyranosyl)-polygalacic acid (virgaureasaponin 5) and 3-O-(beta-D
      glucopyranosyl)-28-O-(alpha-L-rhamnopyranosyl-(1->3)-beta-D-xylopyranosyl-(1->4)
      alpha-L-rhamnopyranosyl-(1->2)-[5-O-acetylapiofuranosyl-(1->3)-[4-O-(3-(3-hydroxy
      1-oxobutoxy)-1-oxobutyl)]-beta-D-fucopyranosyl]-polygalacic acid
      (virgaureasaponin 6). Their structures were established by carrying out 1D and 2D
      NMR experiments along with HRMS analyses. All of the six saponins were evaluated
      to ascertain their inhibition of C. albicans yeast-hyphal conversion, and four of
      them showed significant inhibition.

PMID- 23137725
TI  - Inuloxins A-D, phytotoxic bi-and tri-cyclic sesquiterpene lactones produced by
      Inula viscosa: potential for broomrapes and field dodder management.
AB  - Four phytotoxic bi- and tri-cyclic sesquiterpene lactones, named inuloxins A-D,
      were isolated together with the known alpha-costic acid, from the aerial parts of
      Inula viscosa (family Asteraceae), a widespread Mediterranean plant well known
      for its content of pharmacologically active metabolites. The structures of
      inuloxins A-D were established by spectroscopic and chemical methods and
      determined to be: (4E,7R*,8R*,10S*)-3-oxo-germacra-4,11(13)-dien-8beta-12-olide
      (A), its 11,13-dihydro analogue (B), (5R*,7R*,8R*,10R*)-1,15-methylene-5beta
      hydroxy-eudesm-1(15),11(13)-dien-8beta-12-olide (C), and (7R*,8R*)-1,4-dimethyl-4
      hydroxy-secoeudesm-5(10),11(13)-dien-8beta-12-olide (D). The S absolute
      stereochemistry at C-5 of 5-hydroxyhexan-2-yl side chain of inuloxin D was
      assigned by applying an advanced Mosher's method. The phytotoxic activity of
      inuloxins A-D, that of the diazo and monoacetyl derivatives (of inuloxin A and C,
      resply), as well as that of alpha-costic acid was evaluated against two parasitic
      plant species, i.e. crenate broomrape (Orobanche crenata) and field dodder
      (Cuscuta campestris). Inuloxins A, C and D were the most active on both parasites
      and caused up to 100% inhibition of the seed germination. Inuloxin B was less
      active on Cuscuta and completely inactive against Orobanche. The main metabolite
      alpha-costic acid had a suppressive effect on the dodder seed germination but had
      a stimulating action on the broomrape seed germination. These preliminary results
      allowed to suppose some structure-activity relationships.

PMID- 23137726
TI  - Effect of provenance, plant part and processing on extract profiles from
      cultivated European Rhodiola rosea L. for medicinal use.
AB  - The demand for plant material of Rhodiola rosea L. (Crassulaceae) for medicinal
      use has increased recently, amid concerns about its quality and sustainability.
      We have analysed the content of phenylpropanoids (total rosavins) and salidroside
      in liquid extracts from 3-year old cultivated plants of European origin, and
      mapped the influence of plant part (rhizome versus root), genotype, drying,
      cutting, and extraction solvent to chemical composition. Rhizomes contained 1.5-4
      times more salidroside (0.3-0.4% dry wt) and total rosavins (1.2-3.0%) than
      roots. The qualitative decisive phenylpropanoid content in the extracts was most
      influenced by plant part, solvent, and genotype, while drying temperature and
      cutting conditions were of less importance. We have shown that R. rosea from
      different boreal European provenances can be grown under temperate conditions and
      identified factors to obtain consistent high quality extracts provided that
      authentic germplasm is used and distinguished between rhizome, roots and their
      mixtures.

PMID- 23137727
TI  - Cis-acting motifs in artificially synthesized expression cassette leads to
      enhanced transgene expression in tomato (Solanum lycopersicum L.).
AB  - Efficacy of artificial synthetic expression modules was compared with native
      CaMV35S and DECaMV35S promoter in transgenic tomato developed by Agrobacterium
      mediated transformation. The promoters under trial were CaMV35S-mec (PcamI),
      CaMV35S (PcamII), DECaMV35S (PcamIII), synthetic minimal expression cassette
      (Pmec), complete expression cassette (Pcec), double enhancer expression cassette
      (Pdec) and triple enhancer expression cassette (Ptec) for driving the uidA gene
      for beta-glucuronidase (GUS) activity. The promoter efficiency based on average
      of GUS expression in T(0) and T(1) transgenic tomato was in the order Pcec > Pdec
      > PcamIII > PcamII > PcamI > Ptec > Pmec. The two promoters Pcec and PcamIII were
      deployed for development of insect-resistant transgenic tomato with optimal
      expression of modified cry1Ac insecticidal toxin gene from Bacillus thuringiensis
      (Bt). The transgenic status and copy number of the cry1Ac in T(0) transgenic
      tomato was confirmed through PCR, Southern hybridization, RT-PCR and Western
      immunoassay, while toxin expression was monitored by DAS-ELISA. The expression
      level of Cry1Ac toxin driven by Pcec in T(0) population ranged from 0.08 to 0.8%
      of total soluble protein (TSP) that was significantly higher to PcamIII which
      ranged from 0.02 to 0.13% of TSP. The outcome of insect mortality bioassay with
      Helicoverpa armigera correlated well with the results of DAS-ELISA. The higher
      expression of cry1Ac gene driven by Pcec promoter in transgenic tomato did not
      show any yield penalty and reflected complete protection, while low recovery of
      promising transgenics expressing Cry1Ac toxin driven by PcamIII was a major
      limitation for complete protection against the fruit borer insect.

PMID- 23137728
TI  - The association between adolescent height and student school satisfaction: recent
      evidence from Catalonia.
AB  - We examine the relationship between high-school students' height and their self
      reported school satisfaction. This relationship is explored on the basis of a
      survey conducted in 2008 among some 2200 Catalan (Spanish) students. We find a
      negative association between height and school satisfaction: an association
      apparently correlated with the students' maturity, which in turn influences the
      degree of their disenchantment with the educational system. A 10 cm increase in
      height decreased the probability of falling into the "very satisfied" category by
      9.8%.

PMID- 23137729
TI  - Life-event specificity: bipolar disorder compared with unipolar depression.
AB  - BACKGROUND: Little is known about the impact of different types of stressful
      events (for example divorce v. bereavement) on unipolar depression compared with
      bipolar disorder. Inconsistencies exist concerning the association between
      independent events (beyond an individual's control, such as bereavement) and
      bipolar disorder. AIMS: To examine the role of specific, independent and
      dependent events in mood disorders. METHOD: Life-event information was collected
      from 512 people with bipolar disorder, 1448 people with unipolar depression and
      over 600 controls. RESULTS: Various events were associated with unipolar
      depression and bipolar disorder, but some event specificity was detected. For
      example, financial crisis was more strongly related to bipolar disorder rather
      than unipolar depression. Independent events were only related to unipolar
      depression and not bipolar disorder. CONCLUSIONS: The events that were linked to
      bipolar disorder and unipolar depression were similar. Independent events were
      not associated with bipolar episodes, suggesting that life stress may be a
      consequence of, rather than a trigger for, bipolar episodes.

PMID- 23137730
TI  - Disease burden and mental health system capacity: WHO Atlas study of 117 low- and
      middle-income countries.
AB  - BACKGROUND: Treatment coverage for mental disorders ranges from less than 10% to
      more than 90% across low- and middle-income (LAMI) countries. Studies have yet to
      examine whether the capacity of mental health systems might be adversely affected
      by the burdens of unrelated conditions such as HIV/AIDS. AIMS: To examine whether
      the magnitude of disease burden from communicable, perinatal, maternal and
      nutritional conditions - commonly referred to as Group 1 diseases - is inversely
      associated with mental health system capacity in LAMI countries. METHOD: Multiple
      regression analyses were undertaken using data from 117 LAMI countries included
      in the 2011 World Health Organization (WHO) Mental Health Atlas. Capacity was
      defined in terms of human resources and infrastructure. Regressions controlled
      for effects of political stability, government health expenditures, income
      inequality and neuropsychiatric disease burden. RESULTS: Higher Group 1 disease
      burden was associated with fewer psychiatrists, psychologists and nurses in the
      mental health sector, as well as reduced numbers of out-patient facilities and
      psychiatric beds in mental hospitals and general hospitals (t = -2.06 to -7.68,
      P<0.05). CONCLUSIONS: Evidence suggests that mental health system capacity in
      LAMI countries may be adversely affected by the magnitude of their Group 1
      disease burden.

PMID- 23137731
TI  - Effective treatment of perinatal depression for women in debt and lacking
      financial empowerment in a low-income country.
AB  - BACKGROUND: Poverty may moderate the effect of treatment of depression in low
      income countries. AIMS: To assess poverty and lack of empowerment as moderators
      of a cognitive-behavioural therapy (CBT)-based intervention for perinatal
      depression in rural Pakistan. METHOD: Using secondary analysis of data from a
      randomised controlled trial (trial registration: ISRCTN65316374) we identified
      predictors of depression at 1-year follow-up and moderators of the intervention
      (n = 791). RESULTS: Predictors of follow-up depression included household debt,
      the participant not being empowered to manage household finance and the
      interaction terms for these variables with the trial arm. Effect sizes for women
      with and without household debt were 0.80 and 0.55 respectively. The effect size
      for women in debt and not empowered financially was 0.94 compared with 0.50 for
      women with neither of these factors. CONCLUSIONS: Our findings demonstrate the
      importance of household debt and lack of financial empowerment of women as
      important maintaining factors of depression in low-income countries and our
      locally developed intervention tackled these problems successfully.

PMID- 23137732
TI  - Reactivity of chemical respiratory allergens in the Peroxidase Peptide Reactivity
      Assay.
AB  - Sensitizing chemicals are commonly associated primarily with either skin or
      respiratory sensitization. In the Direct Peptide Reactivity Assay (DPRA), when
      compared with skin sensitizers, respiratory allergens have been demonstrated to
      selectively react with lysine rather than cysteine. The Peroxidase Peptide
      Reactivity Assay (PPRA) has been developed as a refinement to the DPRA. The PPRA
      incorporates dose-response analyses, mass spectroscopy for peptide detection and
      a horseradish peroxidase-hydrogen peroxide enzymatic system, increasing the
      potential to identify pro-haptens. In the investigations reported here, the PPRA
      was evaluated to determine whether it provides advantages for the identification
      of respiratory allergens. Twenty respiratory sensitizers, including five
      predicted to be pre-/pro-haptens were evaluated. The PPRA performed similarly to
      the DPRA with respect to identifying inherently reactive respiratory sensitizers.
      However, three respiratory sensitizers predicted to be pre-/pro-haptens
      (chlorhexidine, ethylenediamine and piperazine) were non-reactive and the general
      selectivity of the respiratory allergens for lysine was lost in the PPRA.
      Overall, the data indicate that the PPRA does not provide an advantage over the
      DPRA for discriminating allergens as either contact or respiratory sensitizers.
      Nevertheless, the PPRA provides a number of refinements to the DPRA that allow
      for an enhanced characterization of reactivity for both classes of chemical
      allergens.

PMID- 23137733
TI  - The role of salivary duct morphology in the aetiology of sialadenitis:
      statistical analysis of sialographic features.
AB  - Morphologic characteristics of salivary ducts may contribute to stagnation of
      saliva. The authors hypothesized that some features might contribute to
      development of submandibular and parotid sialadenitis. 106 digital subtraction
      sialograms (DSS) were retrospectively reviewed for: degree of sialadenitis,
      length of Wharton's and Stensen's ducts (SD), and angle of Wharton's duct (WD)
      genu. Student's t test was used for independent samples to statistically compare
      normal and sialadenitis groups. The effect of independent variables (age, gender,
      side, degree of sialadenitis) on the dependent variable (length or angle) were
      tested using regression analysis. Submandibular duct sialadenitis was mild (67%),
      moderate (8%), or severe (25%); parotid duct sialadenitis was mild (57%),
      moderate (18%), or severe (25%). Mean length of normal WD was 58.2 mm, and 56.3
      mm with sialadenitis. Mean length of normal SD was 52 mm, and 53 mm with
      sialadenitis. The mean angle of WD genu was 115 degrees  in normal ducts, and 119
      degrees  with sialadenitis. None of the independent variables affected variation
      in length or angle. There were no statistical differences in duct length or
      measured angle between normal and sialadenitis groups. There is a wide variation
      in salivary duct morphology but this does not appear to be associated with the
      cause of sialadenitis.

PMID- 23137734
TI  - Significance of clinical stage, extent of surgery and outcome in cutaneous
      squamous cell carcinoma of the head and neck.
AB  - The authors analyzed a new clinical staging system and its correlation with
      pathologic findings and patient survival. Patients were eligible for inclusion in
      this longitudinal retrospective cohort study if they had cutaneous squamous cell
      carcinoma on the head or neck, underwent surgery and had a minimum 3 year follow
      up. The primary study variable was using a new clinical staging system. Secondary
      variables included the parotid as a predictor of metastatic spread to the
      lymphatic nodes in the neck and primary lesion histopathologic traits. The
      outcome variable was patient survival. Associations between variables were
      assessed using Fisher's exact test, Mann-Whitney test, Kaplan-Meier method and
      Mantel log-rank test. p<0.05 was considered significant. The sample comprised 103
      patients. Regional metastatic disease was found in 24 patients. Histopathological
      analysis showed a higher frequency of neck metastatic disease if the parotid was
      positive for metastases (p=0.022). An extended staging system showed significant
      correlation between survival rate and substages (p=0.0105). Perineural invasion
      was a negative prognostic factor (p=0.0151). The results of this study suggest
      that combining curative parotidectomy and elective neck dissection could be
      beneficial in high risk patients. Both neck and parotid metastases should be
      included in the clinical and histological N classification.

PMID- 23137735
TI  - Pathogenesis of African swine fever in domestic pigs and European wild boar.
AB  - African swine fever (ASF) is among the most important viral diseases that can
      affect domestic and feral pigs. Both clinical signs and pathomorphological
      changes vary considerably depending on strain virulence and host factors. Acute
      infections with highly virulent virus strains lead to a clinical course that
      resembles a viral haemorrhagic fever that is characterized by pronounced
      depletion of lymphoid tissues, apoptosis of lymphocyte subsets, and impairment of
      haemostasis and immune functions. It is generally accepted that most lesions can
      be attributed to cytokine-mediated interactions triggered by infected and
      activated monocytes and macrophages, rather than by virus-induced direct cell
      damage. Nevertheless, most pathogenetic mechanisms are far from being understood.
      This review summarizes the current knowledge and discusses implications and
      research gaps.

PMID- 23137736
TI  - Nutrition assessment and management in amyotrophic lateral sclerosis.
AB  - In recent years nutrition assessment and management in amyotrophic lateral
      sclerosis (ALS) have drawn increased attention. Frequent evaluation of nutrition
      status is warranted in ALS, given the common occurrence of dysphagia and
      hypermetabolism and varying disease progression rates. Nutrition management
      includes dietary and swallow strategies, possible gastrostomy tube placement, and
      recommendations for vitamin and mineral supplementation. Strategies to assess and
      optimize nutrition status and prolong survival in ALS patients are reviewed with
      recommendations based on current research.

PMID- 23137738
TI  - Current pharmacologic management in selected neuromuscular diseases.
AB  - For generations, the neuromuscular disorder care community has focused on
      establishing the correct diagnosis and providing supportive care. As the
      pathophysiology and genetics of these conditions became better understood, novel
      treatments targeting the disease mechanism were developed. This has led to some
      significant disease-modifying and supportive treatments for several neuromuscular
      disorders. The current treatments for amyotrophic lateral sclerosis (ALS),
      neuromuscular junction disorders, inflammatory myopathies, and myotonia are
      reviewed. Additionally, investigational treatments for ALS, Duchenne muscular
      dystrophy, and spinal muscular atrophy are discussed.

PMID- 23137740
TI  - Management of pulmonary complications in neuromuscular disease.
AB  - Restrictive lung disease occurs commonly in patients with neuromuscular disease.
      The earliest sign of respiratory compromise in the patient with neuromuscular
      disease is nocturnal hypoventilation, which progresses over time to include
      daytime hypoventilation and eventually the need for full-time mechanical
      ventilation. Pulmonary function testing should be done during regular follow-up
      visits to identify the need for assistive respiratory equipment and initiate
      early noninvasive ventilation. Initiation of noninvasive ventilation can improve
      quality of life and prolong survival in patients with neuromuscular disease.

PMID- 23137737
TI  - Bone health and associated metabolic complications in neuromuscular diseases.
AB  - This article reviews the recent literature regarding bone health as it relates to
      the patient living with neuromuscular disease (NMD). Studies defining the scope
      of bone-related disease in NMD are scant. The available evidence is discussed,
      focusing on abnormal calcium metabolism, increased fracture risk, and the
      prevalence of both scoliosis and hypovitaminosis D in Duchenne muscular
      dystrophy, amyotrophic lateral sclerosis, and spinal muscular atrophy. Future
      directions are discussed, including the urgent need for studies both to determine
      the nature and extent of poor bone health, and to evaluate the therapeutic effect
      of available osteoporosis treatments in patients with NMD.

PMID- 23137741
TI  - Cardiac management in neuromuscular diseases.
AB  - This article addresses the pathophysiology, diagnostic approaches, and
      therapeutic options in the more common forms of muscular dystrophy, especially
      those seen in pediatric and young adult populations. The major emphasis is on the
      dystrophinopathies because their treatment options are templates for those used
      in various other forms of dystrophy. Most patients with cardiomyopathy are
      treated with angiotensin-converting enzyme inhibitors or angiotensin receptor
      blockers, with other agents added as the disease progresses. Destination
      therapies and transplantation options are mentioned where appropriate. Some
      dystrophies can have significant conduction abnormalities requiring pacemaker
      treatment. Others with ventricular tachydysrhythmias may necessitate internal
      cardiac defibrillator placement.

PMID- 23137739
TI  - Novel approaches to corticosteroid treatment in Duchenne muscular dystrophy.
AB  - Although prednisone has never been formally approved for use in Duchenne muscular
      dystrophy (DMD) by regulatory agencies, its efficacy has been confirmed in trials
      dating from the 1980s. There is a strong need for optimization of both specific
      type of glucocorticoid (eg, prednisone, vs deflazacort or others) and the dosing
      regimen. Ideally an optimized regimen would maximize efficacy while minimizing
      side-effect profiles. A new trial, FOR-DMD, aims to address this gap in
      knowledge. In parallel, there has been progress in the area of "dissociative
      steroids," drugs that are able to better separate efficacy and side effects,
      providing a broader therapeutic window.

PMID- 23137742
TI  - Treatment of spine deformity in neuromuscular diseases.
AB  - Surgical management of spinal deformity in neuromuscular diseases (NMDs) often
      requires a multidisciplinary approach beginning in the preoperative surgical
      planning period, owing to concomitant restrictive lung disease and cardiomyopathy
      in selected NMD conditions. The need for thorough and thoughtful discussions must
      occur with the family and other caregivers before any scheduled surgery. The
      decision to proceed with spinal instrumentation may alter functional abilities in
      weak and marginally ambulatory NMD patients. With care and treatment involving a
      multidisciplinary team, proper planning, and support, patients will likely
      experience rewarding outcomes and improved quality of life.

PMID- 23137743
TI  - Mobility-assistive technology in progressive neuromuscular disease.
AB  - Mobility-assistive technologies allow patients with neuromuscular disease to
      interact with peers and the community. In children, they also serve to facilitate
      development. Lack of access to appropriate assistive technology, especially in
      regards to mobility, can have adverse developmental consequences. There are
      multiple options for mobility devices and methods for their control. These
      devices can be integrated with other electronics to facilitate the control of a
      variety of devices in the environment. The clinician should assess which devices
      are best based on the patient's, caregivers', and medical team's goals.

PMID- 23137745
TI  - Using palliative care in progressive neuromuscular disease to maximize quality of
      life.
AB  - This article discusses the role of palliative care in the treatment pathway of
      patients with progressive neuromuscular disease (NDM), including amyotrophic
      lateral sclerosis and Duchenne muscular dystrophy (DMD). People with severe NMDs
      like DMD are now living much longer, well in to adulthood. This makes them
      suitable for the medical model of palliative care. Yet palliative medicine is a
      new area, especially for "adults" with DMD. Strategies for identifying the most
      effective modalities to alleviate suffering in patients with an NMD receiving
      palliative services and creating best practice standards in pain and symptom
      management for this patient population are discussed.

PMID- 23137744
TI  - Chronic pain in neuromuscular disease: pain site and intensity differentially
      impacts function.
AB  - The importance of pain extent (ie, number of body areas with pain) and pain site
      as factors contributing to dysfunction in persons with chronic, slowly
      progressive neuromuscular disease (NMD), remains poorly understood. This article
      discusses the importance of assessing pain site in addition to global pain
      intensity in patients with chronic, slowly progressive NMD. The importance of
      addressing pain at multiple sites will have a major impact on future studies
      assessing interventions to treat pain in this patient population.

PMID- 23137746
TI  - Physical Medicine and Rehabilitation Clinics of North America. Neuromuscular
      disease management and rehabilitation, part II: specialty care and therapeutics.
      Foreword.

PMID- 23137747
TI  - Neuromuscular disease management and rehabilitation, part II: specialty care and
      therapeutics.

PMID- 23137748
TI  - Time course of the antibody response in humans compared with rats experimentally
      infected with hepatic alveolar echinococcosis.
AB  - Human alveolar echinococcosis (AE) is caused by the accidental ingestion of
      Echinococcus multilocularis eggs. Early detection is essential as surgical
      resection is the only treatment for a complete cure. However, details are unclear
      about changes in the antibody response during the initial stages of infection,
      yet such information is useful for early serodiagnosis. Therefore, a long-term
      investigation was performed into the time course of the antibody response before
      'positive' detection. Patient sera were used for enzyme-linked immunosorbent
      assay (ELISA) and Western blotting (WB) analysis using crude antigens extracted
      from E. multilocularis protoscoleces. Rats were experimentally infected with AE
      and similarly analysed by ELISA and WB. Among the markers for diagnoses, the 18
      kDa band (main marker) appeared last in the preoperative stages and disappeared
      first after operation in a WB test. Although the 18 kDa antigen can be useful as
      a marker for AE diagnosis, it cannot contribute to the detection of some patients
      before the 18 kDa band appearance. To avoid misdiagnosis, different diagnostic
      antigens such as the 26-28 and 7-8 kDa bands should also be considered. These
      bands tend to appear earlier than the 18 kDa band and thus offer the potential
      for early detection of AE. We first observed changes in the antibody response in
      a relatively early stage after infection in human AE cases. Notably, changes in
      the antibody response of two intermediate species were similar. These findings
      provide valuable information for the early detection of human AE cases in the
      future. 

PMID- 23137749
TI  - Elevated blood pressure management in acute ischemic stroke remains
      controversial: could this issue be resolved?
AB  - A transient elevated arterial blood pressure is common in acute ischemic stroke
      and is often associated with a poor prognosis. The underlying mechanisms of blood
      pressure elevation are not well understood and its management is still
      unresolved. This article focuses on pathophysiology and management of elevated
      blood pressure in acute ischemic stroke. There is evidence that the main causes
      of a transient blood pressure elevation in acute ischemic stroke are the focal
      cerebral hypoperfusion and the stress responses with neuroendocrine systems
      activation. Clinical trials have reported that blood pressure lowering in acute
      ischemic stroke may have detrimental effect, probably because of impaired
      cerebral autoregulation. However, quantitative assessment of cerebral perfusion
      has not been performed during emergency blood pressure reduction in acute
      ischemic stroke. We suggest that ultrasound carotid artery disease evaluation and
      cerebral hemodynamics monitoring using bilateral transcranial ultrasonography,
      during blood pressure management in acute ischemic stroke might contribute to
      maintaining of an adequate penumbral perfusion and prevent infarct enlargement.
      Such an approach could individualize the antihypertensive treatment in acute
      ischemic stroke and improve functional outcome. Prospective studies are needed to
      confirm such a treatment strategy.

PMID- 23137750
TI  - [Moving from prevention to elimination of mother-to-child transmission of HIV
      before 2015, an unrealistic objective? Social stakes in Senegal].
AB  - In 2010, international agencies began to promote the elimination of mother-to
      child HIV transmission (EMTCT) in 2015 by proposing a new preventive strategy
      based on the extensive use of antiretrovirals. For a country like Senegal where
      the epidemic is considered to be concentrated, since prevalence is beyond 1%, and
      where the prevention program was fully applied to only 7 to 15% of children
      exposed to HIV, the objective is ambitious. The pharmacological efficacy of
      antiretrovirals will not be sufficient if the experience of actors in the field
      about the social aspects and the acceptability of the program to women are not
      considered. The aim of this article is to describe the social issues on the basis
      of two studies conducted in the region of Dakar (an exploratory study of the
      effects of the new prevention strategies and a study of the experience of
      patients receiving antiretroviral treatment for 10 years). The results reveal the
      main issues: community prevention showed its limits at the stage of access to the
      program and test, which suggests the importance of strategies to promote
      awareness and prevention that are focused on women; retention depends highly on
      the attitudes of health workers and on the role of peer counselors, but the
      integration of HIV testing and treatment in reproductive health services is not
      fully established; ambivalent perceptions of antiretrovirals complicate
      adherence; and finally, the organization of health services hinders a family
      approach of prevention. These results are innovative, since most publications on
      this topic concern southern and east Africa.

PMID- 23137751
TI  - Hearing loss in fibromyalgia? Somatic sensory and non-sensory symptoms in
      patients with fibromyalgia and other rheumatic disorders.
AB  - OBJECTIVES: It has been proposed that fibromyalgia can be understood as a
      disorder of central sensitisation and dysregulation (CD) and that characteristic
      somatic symptoms are the result of 'central augmentation'. We examined this
      hypothesis by analysing sensory and non-sensory variables in the context of the
      updated (2010) American College of Rheumatology definition of fibromyalgia and
      the fibromyalgianess (polysymptomatic distress) scale. METHODS: We studied 11,288
      patients, including those with fibromyalgia, rheumatoid arthritis (RA) and
      osteoarthritis (OA). We divided somatic symptoms into sensory (hearing
      difficulties) and evaluative (easy bruising and hair loss) non-sensory symptoms,
      and included a non-symptom that was neutral as to psychological content or
      meaning (influenza vaccination). Data were analysed by logistic regression and
      adjusted for age and sex. RESULTS: Fibromyalgia patients reported more sensory
      and non-sensory symptoms than patients with RA and OA, but not more non-symptoms.
      At all levels of fibromyalgianess (or fibromyalgia intensity) the probability of
      sensory and non-sensory symptoms was similar across all rheumatic diseases, and
      this association occurred in FM criteria (+) and criteria (-) patients. No
      association was noted with the non-symptom control question. CONCLUSIONS: While
      the CD hypothesis is consistent with hearing problems in fibromyalgia, there is
      no medical explanation for the evaluative symptoms of hair loss and bruising
      being increased. The associations between fibromyalgia/fibromyalgianess and
      evaluative (not sensory) symptoms must occur through mechanisms other than
      central sensitization and augmentation, and are consistent with over-reporting
      that has a psychological basis. However, augmentation of sensory symptoms does
      not preclude simultaneous over-reporting.

PMID- 23137752
TI  - Providing care for children with severe acute malnutrition in India: new evidence
      from Jharkhand.
AB  - OBJECTIVE: To assess the effectiveness of facility-based care for children with
      severe acute malnutrition (SAM) in malnutrition treatment centres (MTC). DESIGN:
      Early detection and treatment of SAM using locally adapted protocols; assessment
      of programme outcomes, including survival, default, discharge and recovery rates.
      SETTING: All forty-eight MTC in Jharkhand, India. SUBJECTS: Children (n 3595)
      with SAM admitted to MTC (1 July 2009-30 June 2011). RESULTS: Of children
      admitted, 55.0% were girls, 77.7% were 6-23 months old and 68.6% belonged to
      scheduled tribes or castes; 34.4% had oedema or medical complications. Of the
      3418 programme exits, the proportion of children who died was 0.6% (n 20), the
      proportion of children who defaulted was 18.4% (n 628) and the proportion of
      children discharged was 81.0% (n 2770). Children's average weight gain was 9.6
      (sd 8.4) g/kg body weight per d and their average length of stay was 16.0 (sd
      5.7) d. Among the 2770 children who were discharged from the programme, 39.4% (n
      1090) gained 15 % or more of their initial weight while 60.6% (n 1680) gained
      less than 15 % of their initial weight. CONCLUSIONS: MTC provide live-saving care
      for children with SAM as demonstrated by high survival rates. However, the
      protocols and therapeutic foods currently used need to improve to ensure the
      recovery of all discharged children. MTC should be reserved for children with
      complicated SAM; children with uncomplicated SAM should be admitted to a
      community-based programme for the management of SAM, at a lesser risk to children
      and a lesser cost to families and the health system.

PMID- 23137753
TI  - Flow cytometry-assisted rapid isolation of recombinant Plasmodium berghei
      parasites exemplified by functional analysis of aquaglyceroporin.
AB  - The most critical bottleneck in the generation of recombinant Plasmodium berghei
      parasites is the mandatory in vivo cloning step following successful genetic
      manipulation. This study describes a new technique for rapid selection of
      recombinant P. berghei parasites. The method is based on flow cytometry to
      isolate isogenic parasite lines and represents a major advance for the field, in
      that it will speed the generation of recombinant parasites as well as cut down on
      animal use significantly. High expression of GFP during blood infection, a
      prerequisite for robust separation of transgenic lines by flow cytometry, was
      achieved. Isogenic recombinant parasite populations were isolated even in the
      presence of a 100-fold excess of wild-type (WT) parasites. Aquaglyceroporin (AQP)
      loss-of-function mutants and parasites expressing a tagged AQP were generated to
      validate this approach. aqp(-) parasites grow normally within the WT phenotypic
      range during blood infection of NMRI mice. Similarly, colonization of the insect
      vector and establishment of an infection after mosquito transmission were
      unaffected, indicating that AQP is dispensable for life cycle progression in vivo
      under physiological conditions, refuting its use as a suitable drug target.
      Tagged AQP localized to perinuclear structures and not the parasite plasma
      membrane. We suggest that flow-cytometric isolation of isogenic parasites
      overcomes the major roadblock towards a genome-scale repository of mutant and
      transgenic malaria parasite lines.

PMID- 23137754
TI  - The association between precancerous gastric lesions and serum pepsinogens, serum
      gastrin, vascular endothelial growth factor, serum interleukin-1 Beta, serum toll
      like receptor-4 levels and Helicobacter pylori Cag A status.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to investigate the
      association between serum pepsinogens, serum gastrin, serum vascular endothelial
      growth factor, serum interleukin-1 Beta, serum toll-like receptor-4 levels and
      Helicobacter pylori Cag A status in patients with various gastric precancerous
      lesions. METHODS: One hundred and sixty two consecutive patients with various
      gastric lesions [38 (23.5%) H. pylori positive chronic non-atrophic gastritis, 45
      (27.8%) autoimmune gastritis, 42 intestinal metaplasia and 37 dysplasia] were
      enrolled into the study. Serum pepsinogen I and II, gastrin 17, vascular
      endothelial growth factor, interleukin-1 Beta, toll-like receptor-4 levels, H.
      pylori Cag A status were evaluated. RESULTS: H. pylori was positive in 98 (60.5%)
      patients and 38 of these patients were Cag A positive. Serum pepsinogen level was
      significantly lower in patients with autoimmune atrophic gastritis compared to
      the patients with non-atrophic chronic gastritis (p<0.001), intestinal metaplasia
      (P<0.001) and dysplasia (P=0.002). Mean serum gastrin was 1209.6+/-268.48 pg/mL
      in patients with autoimmune atrophic gastritis and 234.95+/-184.018 pg/mL in
      patients with chronic non-atrophic gastritis. Mean toll-like receptor-4 level was
      0.56+/-0.098 ng/mL in patient with dysplasia, and this value was higher compared
      to patients with chronic non-atrophic gastritis (P=0.007), autoimmune atrophic
      gastritis (P=0.003) and intestinal metaplasia (P=0.006). Interleukin-1 Beta level
      was significantly lower in patients with dysplasia compared to patients with
      chronic non-atrophic gastritis (P=0.034). CONCLUSIONS: Serum pepsinogens, serum
      gastrin and H. pylori Cag A status are important tests in detecting gastric
      precancerous lesions. However, toll-like receptor-4 may be a sensitive test to
      differentiate the patients with dysplasia from the other precancerous gastric
      lesions. Non-invasive tests are sensitive in the diagnosis of gastric
      precancerous lesions.

PMID- 23137755
TI  - Intrapancreatic accessory spleen located within the tail of the pancreas.

PMID- 23137756
TI  - Diaphragmatic necrosis after radiofrequency ablation of hepatocellular carcinoma:
      a successful surgical repair.
AB  - We report a case of complete hemidiaphragmatic necrosis with liver abscess
      complicating radiofrequency ablation of a large subdiaphragmatic hepatocellular
      carcinoma in a patient with unrecognized history of endoscopic oddi
      sphincterotomy. At 2-year follow-up after surgical repair using a pedicled
      latissimus dorsi flap, clinical examination and imaging did not show complication
      or cancer recurrence. The risk of complete hemidiaphragmatic necrosis resulting
      from both thermal and septic injuries should be considered when radiofrequency
      ablation is performed for liver dome tumors, particularly in patients with
      impaired oddi sphincter. In this septic situation, a latissimus dorsi flap
      appears as the unique opportunity to repair the injured hemidiaphragm.

PMID- 23137757
TI  - Synchronous gastric cancer presenting different pathological features depending
      on the involvement of Epstein-Barr virus infection.

PMID- 23137758
TI  - Genetic polymorphisms of ICAM 1 and IL28 as predictors of liver fibrosis severity
      and viral clearance in hepatitis C genotype 4.
AB  - BACKGROUND AND OBJECTIVES: Intercellular adhesion molecule-1 (ICAM-1) is located
      on chromosome 19p13.2, and this protein plays an important role in the
      pathogenesis of the hepatitis C virus (HCV). The rs12979860 polymorphism of the
      IL-28B gene participates in HCV clearance. This study investigated the
      association of the genetic markers (SNPs), rs5496, rs281437 and rs12979860
      polymorphisms, with viral clearance and the progression of hepatic fibrosis in
      HCV genotype 4 patients who were treated with pegylated interferon and ribavirin.
      METHODS: Thirty consecutive HCV genotype 4 patients who were treated with
      pegylated interferon and ribavirin therapy for 48 weeks were grouped into
      responders (control group) and non-responders (case group). The severity of
      fibrosis was classified according to the Scheuer Score. SNP genotyping of rs5496
      [A/G], rs281437 [C/T] and rs12979860 [C/T] were performed using the 5' nuclease
      assay with a TaqMan MGB probe in an ABI 7500 Fast Real-Time PCR System (Applied
      Biosystems). RESULTS: All SNPs exhibited Hardy-Weinberg Equilibrium (HWE). The
      patients with the C allele of rs12979860 exhibited an approximately eight times
      higher risk of SVR compared to patients with the T allele (aOR=7.98; CI: 1.07
      59.36, P=0.012). No significant association of rs5496 and rs281437 with treatment
      response was detected (P=0.185 and P=0.123, respectively). Patients with the T
      allele of rs281437 exhibited an approximately 13 times higher risk of severe
      fibrosis compared to patients with the C allele (aOR=13.0; CI: 1.32-128.11, P=
      0.028). No significant association of the other genetic variants with the degree
      of fibrosis in the study subjects was detected for rs5496 and rs12979860.
      CONCLUSION: The present study revealed associations between the ICAM-1 gene
      marker, rs281437, and the progression of hepatic fibrosis in HCV genotype 4 and
      rs12979860 of the IL-28 B gene with viral clearance.

PMID- 23137759
TI  - Endometrin as luteal phase support in assisted reproduction.
AB  - OBJECTIVE: To compare clinical pregnancy rate (PR) and live birth rate (LBR)
      between Endometrin monotherapy versus Endometrin and P in oil combination therapy
      in assisted reproductive technology (ART) cycles. DESIGN: Retrospective analysis.
      SETTING: Large private practice. PATIENT(S): Patients undergoing autologous fresh
      IVF cycles, autologous frozen ET cycles, and fresh oocyte donor cycles were
      included for analysis. INTERVENTION(S): Endometrin as a single agent for luteal
      support, Endometrin monotherapy or Endometrin with P in oil used at least once
      every 3 days for luteal support, Endometrin combination therapy. MAIN OUTCOME
      MEASURE(S): Clinical PR and LBR. RESULT(S): A total of 1,034 ART cycles were
      analyzed. Endometrin monotherapy was used in 694 of 1,034 (67%) cycles and
      Endometrin combination therapy was used in 340 of 1,034 (33%) cycles. In all
      fresh cycles, clinical PR was not significantly different (IVF autologous:
      Endometrin monotherapy 46.9% vs. Endometrin combination therapy 55.6%; donor
      oocyte endometrin monotherapy 45.2% vs. Endometrin combination therapy 52.0%).
      Frozen ET cycles had a significantly higher clinical PR and LBR with combination
      therapy group compared with monotherapy (clinical PR 47.9% vs. 23.5%; LBR 37.5%
      vs. 17.3%). CONCLUSION(S): Endometrin monotherapy was sufficient for the P
      component of luteal support and provided high PRs for fresh cycles in both
      autologous and donor oocyte cycles. Clinical PR and LBR in frozen ET cycles were
      significantly improved with the addition of IM P to Endometrin therapy. This may
      reflect the fact that lesser quality embryos are transferred in frozen ET cycles,
      and more intense P support is required for comparable PRs.

PMID- 23137760
TI  - Quantification of nucleolar channel systems: uniform presence throughout the
      upper endometrial cavity.
AB  - OBJECTIVE: To determine the prevalence of nucleolar channel systems (NCSs) by
      uterine region, applying continuous quantification. DESIGN: Prospective clinical
      study. SETTING: Tertiary care academic medical center. PATIENT(S): Forty-two
      naturally cycling women who underwent hysterectomy for benign indications.
      INTERVENTION(S): NCS presence was quantified by a novel method in six uterine
      regions-fundus, left cornu, right cornu, anterior body, posterior body, and lower
      uterine segment (LUS)-with the use of indirect immunofluorescence. MAIN OUTCOME
      MEASURE(S): Percentage of endometrial epithelial cells (EECs) with NCSs per
      uterine region. RESULT(S): NCS quantification was observer independent
      (intraclass correlation coefficient 0.96) and its intrasample variability low
      (coefficient of variation 0.06). Eleven of 42 hysterectomy specimens were
      midluteal, ten of which were analyzable with nine containing >5% EECs with NCSs
      in at least one region. The percentage of EECs with NCSs varied significantly
      between the LUS (6.1%; interquartile range [IQR] 3.0-9.9) and the upper five
      regions (16.9%; IQR 12.7-23.4), with fewer NCSs in the basal layer of the
      endometrium (17 +/- 6%) versus the middle (46 +/- 9%) and luminal layers (38 +/-
      9%) of all six regions. CONCLUSION(S): NCS quantification during the midluteal
      phase demonstrates uniform presence throughout the endometrial cavity, excluding
      the LUS, with a preference for the functional luminal layers. Our quantitative
      NCS evaluation provides a benchmark for future studies and further supports NCS
      presence as a potential marker for the window of implantation.

PMID- 23137761
TI  - The affordable care act's impact on fertility care.
AB  - The Supreme Court's decision upholding the constitutionality of the Affordable
      Care Act (ACA) provides an opportunity to review its impact on fertility care in
      the United States. After examining the legislation, we identified several core
      areas that might affect patients struggling with infertility. Although changes to
      the tax code, elimination of denying insurance to those with pre-existing
      conditions, and an overriding theme of maternity care within the ACA are easy to
      qualify and quantify, due to the incremental nature of the ACA, it remains to be
      seen whether the ACA will alter the current status quo of access to fertility
      care.

PMID- 23137762
TI  - [Conservative management in a patient with missile cardiac wounds].

PMID- 23137763
TI  - Revisiting causal neighborhood effects on individual ischemic heart disease risk:
      a quasi-experimental multilevel analysis among Swedish siblings.
AB  - Neighborhood socioeconomic disadvantage is associated to increased individual
      risk of ischemic heart disease (IHD). However, the value of this association for
      causal inference is uncertain. Moreover, neighborhoods are often defined by
      available administrative boundaries without evaluating in which degree these
      boundaries embrace a relevant socio-geographical context that condition
      individual differences in IHD risk. Therefore, we performed an analysis of
      variance, and also compared the associations obtained by conventional multilevel
      analyses and by quasi-experimental family-based design that provides stronger
      evidence for causal inference. Linking the Swedish Multi-Generation Register to
      several other national registers, we analyzed 184,931 families embracing 415,540
      full brothers 45-64 years old in 2004, and residing in 8408 small-area market
      statistics (SAMS) considered as "neighborhoods" in our study. We investigated the
      association between low neighborhood income (categorized in groups by deciles)
      and IHD risk in the next four years. We distinguished between family mean and
      intrafamilial-centered low neighborhood income, which allowed us to investigate
      both unrelated individuals from different families and full brothers within
      families. We applied multilevel logistic regression techniques to obtain odds
      ratios (OR), variance partition coefficients (VPC) and 95% credible intervals
      (CI). In unrelated individuals a decile unit increase of low neighborhood income
      increased individual IHD risk (OR = 1.04, 95% CI: 1.03-1.07). In the
      intrafamilial analysis this association was reduced (OR = 1.02, 95% CI: 1.02
      1.04). Low neighborhood income seems associated with IHD risk in middle-aged men.
      However, despite the family-based design, we cannot exclude residual confounding
      by genetic and non-shared environmental factors. Besides, the low neighborhood
      level VPC = 1.5% suggest that the SAMS are a rather inappropriate construct of
      the socio-geographic context that conditions individual variance in IHD risk. In
      contrast the high family level VPC = 20.1% confirms the relevance of the family
      context for understanding IHD risk.

PMID- 23137764
TI  - Antiangiogenic agents as a maintenance strategy for advanced epithelial ovarian
      cancer.
AB  - Bevacizumab is the first antiangiogenic agent to have demonstrated benefit as
      first-line and maintenance therapy in epithelial ovarian cancer (EOC), with the
      Gynecologic Oncology Group 218 and ICON 7 phase III trials revealing
      significantly prolonged progression-free survival (PFS) for
      carboplatin/paclitaxel plus bevacizumab followed by bevacizumab maintenance
      versus carboplatin/paclitaxel alone. Results are forthcoming from several phase
      III maintenance trials of investigational antiangiogenic agents, each evaluating
      PFS as the primary endpoint: AGO-OVAR12/LUME-Ovar1 (nintedanib [BIBF 1120]), AGO
      OVAR16 (pazopanib), and TRINOVA-1, -2, and -3 (AMG 386). Here we review available
      data and ongoing clinical trials of investigational antiangiogenic agents as
      maintenance therapy for EOC. Current controversies, including uncertainties
      regarding the (1) most appropriate clinical trial endpoints, (2) optimal dosing,
      duration, and timing of therapy (e.g., with first-line chemotherapy and/or as
      maintenance monotherapy), and (3) feasibility, tolerability, and cost of adding
      these agents to platinum/taxane regimens are also highlighted.

PMID- 23137766
TI  - Clinical management of drug-drug interactions in HCV therapy: challenges and
      solutions.
AB  - Hepatitis C virus (HCV) infected patients often take multiple co-medications to
      treat adverse events related to HCV therapy, or to manage other co-morbidities.
      Drug-drug interactions associated with this polypharmacy are relatively new to
      the field of HCV pharmacotherapy. With the advent of the direct-acting antivirals
      telaprevir and boceprevir, which are both substrates and inhibitors of the
      cytochrome P450 (CYP) 3A iso-enzyme, knowledge and awareness of drug-drug
      interactions have become a cornerstone in the evaluation of patients starting and
      continuing HCV combination therapy. In our opinion, an overview of conducted drug
      drug interaction studies and a list of contraindicated medications is not enough
      for the clinical management of these drug-drug interactions. Knowledge of
      pharmacokinetic profiles and concentration-effect relationships is key for the
      interpretation of these data, and insight into how to manage these interactions
      (e.g., dose adjustments, safe alternatives and therapeutic drug monitoring) is of
      equal importance. This review provides a practical overview of the safe and
      effective management of these clinical challenges.

PMID- 23137767
TI  - To use or not to use--practitioners' perceptions of an open web portal for young
      patients with diabetes.
AB  - BACKGROUND: Health care professionals' attitudes can be a significant factor in
      their acceptance and efficient use of information technology, so they need to
      have more knowledge about this resource to enhance their participation.
      OBJECTIVE: We explored practitioners' perceptions of using an open-access
      interactive Web portal tailored to young diabetes type 1 patients and their
      guardians or significant others. The portal offered discussion forums, blog
      tools, self-care and treatment information, research updates, and news from local
      practitioners. METHODS: Eighteen professionals who were on pediatric diabetes
      care teams each wrote an essay on their experience using the portal. For their
      essays, they were asked to describe two situations, focusing on positive and
      negative user experiences. The essays were analyzed using qualitative content
      analysis. RESULTS: Based on our analysis of the respondents essays, we identified
      three categories that describe perceptions of the Web portal.   The first
      category - to use or not to use - included the different perspectives of the
      practioners; those who questioned the benefits of using the Web portal or showed
      some resistance to using it. The frequency of use among the practitioners varied
      greatly. Some practitioners never used it, while others used it on a daily basis
      and regularly promoted it to their patients. Some respondents in this category
      reflected on the benefits of contributing actively to online dialogues.   In the
      second category - information center for everyone - practitioners embraced the
      site as a resource for scientifically sound information and advice. As part of
      their practice, and as a complement to traditional care, practitioners in this
      category described sending information through the portal to patients and their
      significant others. Practitioners felt safe recommending the site because they
      knew that the information provided was generated by other practitioners. They
      also assumed that their patients benefited from actively using the Web portal at
      home: peers brought the site to life by exchanging experiences through the
      discussion forums.   In the third category - developing our practice -
      practitioners reflected upon the types of information that should be given to
      patients and how to give it (ie, during in-person appointments or through the Web
      portal). They perceived meeting with various professionals at other hospitals to
      update information on the portal and develop content policies as constructive
      teamwork. Practitioners expressed interest in reading patients' dialogues online
      to learn more about their views. They also thought about how they could use the
      portal to adapt more to patients' needs (eg, creating functions so patients could
      chat with the diabetes nurses and doctors). CONCLUSIONS: Practitioners expressed
      positive perceptions toward a tailored open Web portal. They suggested that
      future benefits could be derived from systems that integrate factual information
      and online dialogues between practitioners and patients (ie, exchanging
      information for everyone's benefit).

PMID- 23137765
TI  - Achievement of therapeutic targets in Mexican patients with diabetes mellitus.
AB  - BACKGROUND AND AIM: Complications of diabetes comprise the leading cause of death
      in Mexico. We aimed to describe the characteristics of management and achievement
      of therapeutic targets in Mexican patients with diabetes mellitus. METHODS: We
      analyzed data from 2642 Mexican patients with type 1 (T1D, n=203, 7.7%) and type
      2 diabetes (T2D, n=2439, 92.3%) included in the third wave of the International
      Diabetes Management Practices Study. RESULTS: Of T2D patients, 63% were on oral
      glucose-lowering drugs (OGLD) exclusively (mostly metformin), 11% on insulin, 22%
      on OGLD plus insulin, and 4% on diet and exercise exclusively. T2D patients on
      insulin were more likely to be trained on diabetes, but they were older, had
      worse control, longer disease duration and more chronic complications than
      patients on OGLD only. Glycated hemoglobin (HbA1c) <7% was achieved by 21% and
      37% of T1D and T2D patients, respectively. Only 5% of T1D and 3% of T2D attained
      the composite target of HbA1c <7%, blood pressure <130/80 mmHg and low-density
      lipoprotein cholesterol <100 mg/dl. T1D patients had less macrovascular but more
      microvascular complications, compared with T2D patients. Late complications
      increased with disease duration, so that about 80% of patients after 20 years of
      diagnosis have at least one late complication. Reaching the target HbA1c <7% was
      associated with a reduced number of microvascular but not with less macrovascular
      complications. CONCLUSION: A great proportion of these Mexican patients with
      diabetes did not reach therapeutic targets. Insulin was used mostly in
      complicated cases with advanced disease.

PMID- 23137768
TI  - Management of trypanosomiasis and leishmaniasis.
AB  - BACKGROUND: The current treatments for human African trypanosomiasis (HAT),
      Chagas disease and leishmaniasis (collectively referred to as the kinetoplastid
      diseases) are far from ideal but, for some, there has been significant recent
      progress. For HAT the only advances in treatment over the past two decades have
      been the introduction of an eflornithine/nifurtimox co-administration and a
      shorter regime of the old standard melarsoprol. SOURCES OF DATA: PubMed. AREAS OF
      AGREEMENT: There is a need for new safe, oral drugs for cost-effective treatment
      of patients and use in control programmes for all the trypanosomatid diseases.
      AREAS OF CONTROVERSY: Cutaneous leishmaniasis is not on the agenda and treatments
      are lagging behind. GROWING POINTS: There are three compounds in development for
      the treatment of the CNS stage of HAT: fexinidazole, currently due to entry into
      phase II clinical studies, a benzoxaborole (SCYX-7158) in phase I trials and a
      diamidine derivative (CPD-0802), in advanced pre-clinical development. For Chagas
      disease, two anti-fungal triazoles are now in clinical trial. In addition,
      clinical studies with benznidazole, a drug previously recommended only for acute
      stage treatment, are close to completion to determine the effectiveness in the
      treatment of early chronic and indeterminate Chagas disease. For visceral
      leishmaniasis new formulations, therapeutic switching, in particular AmBisome,
      and the potential for combinations of established drugs have significantly
      improved the opportunities for the treatment in the Indian subcontinent, but not
      in East Africa. AREAS TIMELY FOR DEVELOPING RESEARCH: Improved diagnostic tools
      are needed to support treatment, for test of cure in clinical trials and for
      monitoring/surveillance of populations in control programmes.

PMID- 23137769
TI  - A novel cinnamate derivative attenuates asthma features and reduces bronchial
      epithelial injury in mouse model.
AB  - Airway epithelial injury is the hallmark of various respiratory diseases and
      therapeutic targeting of epithelial injury could be an effective strategy for
      controlling these diseases. We recently reported that a novel cinnamate, ethyl
      3',4',5'-trimethoxythionocinnamate (ETMTC) derived from Piper longum derivative,
      was most potent among various cinnamate derivatives in inhibiting inflammatory
      cell adhesion molecules (CAMs). In this study, we investigated the effects of
      ETMTC on the features of allergic asthma and epithelial injury in a murine model.
      ETMTC treatment to ovalbumin sensitized and challenged mice during ovalbumin
      challenge reduced airway hyperresponsiveness, and airway inflammation. This
      attenuation of asthma features was associated with the reduction in the
      expressions of various CAMs, NF-kappaB activation, Th2 cytokines, eotaxin and 8
      isoprostane that were estimated in lung homogenates. Further, it increased
      activities of mitochondrial complexes I and IV in lung mitochondria and reduced
      cytochrome c and caspase 9 activities in lung cytosol. In addition, it reduced
      the levels of oxidative DNA damage marker in bronchoalveolar lavage fluid and DNA
      fragmentation of bronchial epithelia in lung sections. Further, ETMTC not only
      increased the levels of 15-(S)-hydroxyeicosatetraenoic acid, suppressor of airway
      remodeling, but also inhibited goblet cell metaplasia and sub-epithelial
      fibrosis. These results demonstrate that ETMTC reduces epithelial injury and
      mitochondrial dysfunction associated with allergic asthma and thus ETMTC could be
      useful to develop efficient therapeutic molecule against asthma.

PMID- 23137770
TI  - Placebo and nocebo responses in randomised controlled trials of drugs applying
      for approval for fibromyalgia syndrome treatment: systematic review and meta
      analysis.
AB  - OBJECTIVES: The superiority of true drug treatment over placebo in reducing
      symptoms of fibromyalgia syndrome (FMS) is small and bought by relevant rates of
      drop-outs due to adverse events. Recent systematic reviews demonstrated that a
      substantial proportion of the beneficial and adverse effects of true drug is
      attributable to placebo in chronic pain trials. We determined the magnitude of
      the placebo and nocebo response and its impact on the benefits and harms of true
      drug in trials of drugs which were submitted for approval for treatment of FMS.
      METHODS: CENTRAL, MEDLINE and clinicaltrials.gov were searched from inception to
      June 30, 2012 for randomized double-blind placebo controlled trials with a
      parallel design for duloxetine, milnacipran, pregabalin and sodium oxybate in FMS
      patients. The magnitude of placebo response was assessed by the pooled estimate
      of a 50% placebo pain reduction. The magnitude of nocebo response was determined
      by the pooled estimate of drop-out rates due to adverse events in placebo groups.
      RESULTS: 18 studies with 3546 patients on placebo were included. The pooled
      estimate of a 50% pain reduction by placebo was 18.6% (95% CI 17.4 to 19.9%). The
      pooled estimate of drop-out due to adverse events in placebo groups was 10.9%
      (95% CI 9.9 to 11.9%). CONCLUSIONS: The magnitude of placebo and nocebo response
      in trials of drugs applying for approval for FMS treatment was substantial. Study
      investigators aim to reduce placebo response. By contrast, clinicians often
      utilise placebo effects. Strategies to reduce nocebo responses in clinical trials
      and practice should be developed.

PMID- 23137771
TI  - Can clouds dance? Part 2: an ERP investigation of passive conceptual expansion.
AB  - Conceptual expansion, one of the core operations in creative cognition, was
      investigated in the present ERP study. An experimental paradigm using novel
      metaphoric, nonsensical and literal phrases was employed where individual
      differences in conceptual knowledge organization were accounted for by using
      participants' responses to categorize the stimuli to each condition. The
      categorization was determined by their judgment of the stimuli on the two
      defining criteria of creativity: unusualness and appropriateness. Phrases judged
      as unusual and appropriate were of special interest as they are novel and
      unfamiliar phrases thought to passively induce conceptual expansion. The results
      showed a graded N400 modulation for phrases judged to be unusual and
      inappropriate (nonsense) or unusual and appropriate (conceptual expansion, novel
      metaphorical) relative to usual and appropriate (literal) phrases. The N400 is
      interpreted as indexing greater effort to retrieve semantic information and
      integrate the novel concepts presented through the phrases. Analyses of the later
      time-window showed an ongoing negativity that was graded in the same manner as
      the N400. The findings attest to the usefulness of investigating creative
      cognition using event-related electrophysiology.

PMID- 23137772
TI  - A genome-wide approach to comparative oncology: high-resolution oligonucleotide
      aCGH of canine and human osteosarcoma pinpoints shared microaberrations.
AB  - Molecular cytogenetic evaluation of human osteosarcoma (OS) has revealed the
      characteristically high degree of genomic reorganization that is the hallmark of
      this cancer. The extent of genomic disorder in OS has hindered identification of
      the genomic aberrations driving disease progression. With pathophysiological
      similarities to its human counterpart, canine OS represents an ideal model for
      comparison of conserved regions of genomic instability that may be disease
      associated rather than genomic passengers. This study used high-resolution
      oligonucleotide array comparative genomic hybridization and a variety of
      informatics tools to aid in the identification of disease-associated genome-wide
      DNA copy number aberrations in canine and human OS. Our findings support and
      build upon the high level of cytogenetic complexity, through the identification
      of shared regions of microaberration (<500 kb) and functional analysis of
      possible orthologous OS-associated genes to pinpoint the cellular processes most
      commonly affected by aberration in human and canine OS. Aberrant regions
      contained previously reported genes such as CDC5L, MYC, RUNX2, and CDKN2A/CDKN2B,
      while expanding the gene of interest list to include ADAM15, CTC1, MEN1, CDK7,
      and others. Such regions of instability may thus have functional significance in
      the etiology of OS, the most common primary bone tumor in both species.

PMID- 23137773
TI  - Mitroflow pericardial bioprosthesis: structured failure at 4.5 years.
AB  - BACKGROUND: Prosthetic heart valves are commonly used in the management of
      significant valvular disease. Although bioprostheses are increasingly popular,
      structural deterioration with cusp tears and calcification persists. METHODS: We
      present a case of a Mitroflow pericardial bioprosthesis (Sorin Group Inc.,
      Mitroflow Division, Vancouver, Canada) explanted after 4.5 years from a 78-year
      old woman for bioprosthesis stenosis. RESULTS: The morphological reasons for
      bioprosthesis failure include structural tissue deterioration with thickening of
      the pericardial cusps, cusp calcification, and parastent post tears resulting in
      significant valvular dysfunction. CONCLUSION: To the best of our knowledge, this
      is the first detailed morphological description of the failure modes of a
      surgically explanted Mitroflow (A12) pericardial bioprosthesis.

PMID- 23137774
TI  - Strategies to improve diet in older adults.
AB  - It is estimated that by 2050 there will be 2 billion people aged 60 years and
      older in the world. The evidence base for the health benefits of good nutrition
      and physical activity, as well as weight loss among overweight and obese adults,
      is growing and a number of policies and guidelines are available to guide health
      professionals in serving older people at various stages of the lifecycle. There
      are many potential influences on dietary habits including individual factors,
      families and friends, community characteristics, the food and supplement
      industry, and public policy. This review focuses on the evidence base for factors
      influencing diet in older adults, food insecurity, Na, vitamin D, vitamin B12,
      protein, obesity and the benefits of energy restriction in overweight and obese
      older adults. Research is needed to continue to increase the evidence base for
      appropriate ways to improve diet and health in older people. Also, much of the
      available information is from the US, so there is a need to conduct research in
      other areas of the world.

PMID- 23137775
TI  - Human repetitive sequence densities are mostly negatively correlated with R/Y
      based nucleosome-positioning motifs and positively correlated with W/S-based
      motifs.
AB  - We examined statistical correlations between the frequencies of seven proposed
      nucleosome positioning motifs and the densities of repetitive sequences in the
      human genome. For both parametric and non-parametric measures of statistical
      correlations there is a tendency for repetitive sequence density to be negatively
      correlated with the density of R/Y-based nucleosome positioning motifs, while
      being positively correlated with that of W/S-based motifs. These results largely
      hold even when motifs are examined only within repeat-filtered sequences. The
      RRRRRYYYYY motif and its 5-base shift YYYYYRRRRR, in particular, is over
      represented in the human genome; and its negative correlation is consistently
      present at different regions and at different length scales. For some other
      nucleosome positioning motifs, the relationship with repeats can be regional or
      length scale dependent. Considering the importance of nucleosome formation in
      epigenetic regulations, these results may provide new insight to the evolution of
      repetitive sequences. 

PMID- 23137776
TI  - When integration fails: Prokaryote phylogeny and the tree of life.
AB  - Much is being written these days about integration, its desirability and even its
      necessity when complex research problems are to be addressed. Seldom, however, do
      we hear much about the failure of such efforts. Because integration is an ongoing
      activity rather than a final achievement, and because today's literature about
      integration consists mostly of manifesto statements rather than precise
      descriptions, an examination of unsuccessful integration could be illuminating to
      understand better how it works. This paper will examine the case of prokaryote
      phylogeny and its apparent failure to achieve integration within broader tree-of
      life accounts of evolutionary history (often called 'universal phylogeny').
      Despite the fact that integrated databases exist of molecules pertinent to the
      phylogenetic reconstruction of all lineages of life, and even though the same
      methods can be used to construct phylogenies wherever the organisms fall on the
      tree of life, prokaryote phylogeny remains at best only partly integrated within
      tree-of-life efforts. I will examine why integration does not occur, compare it
      with integrative practices in animal and other eukaryote phylogeny, and reflect
      on whether there might be different expectations of what integration should
      achieve. Finally, I will draw some general conclusions about integration and its
      function as a 'meta-heuristic' in the normative commitments guiding scientific
      practice. 

PMID- 23137777
TI  - Is treatment with hydroxychloroquine effective in surfactant protein C
      deficiency?
AB  - We present the case of two twin brothers with surfactant protein C deficiency who
      were treated with hydroxychloroquine for three years, with apparent success. The
      exact physiopathology of this disease is not known and there is no specific
      treatment for it. There is merely news from a few previous descriptions in the
      literature about the use of hydroxychloroquine for surfactant protein C
      deficiency with satisfactory results. Two years after the treatment was
      withdrawn, the twins were evaluated once again: they presented no new infections,
      growth and general state were normal and chest CT showed a notable additional
      reduction in the interstitial pneumopathy. These data seem to cast some doubt on
      the efficacy of hydroxychloroquine, and they suggest that the clinical
      improvement was simply the natural evolution of the disease.

PMID- 23137778
TI  - The day hospital: analysis of results, costs and management of pneumology
      resources.
AB  - BACKGROUND: Day hospital units specialized in pulmonology are a relatively new
      instrument for providing care to complex respiratory patients. However, the
      number of studies focused on the efficacy and efficiency of day hospitals is
      scarce. AIM: Therefore, the aim of the present study was to analyze the effects
      of implementing a specialized respiratory day hospital in a standard teaching
      hospital with 500 beds. METHODS: An analysis of efficacy, efficiency and quality
      care. RESULTS: Throughout the study period (2 years) the day hospital
      progressively increased its activity. Although patient pressure on the emergency
      department remained constant, this was associated with a parallel increase in the
      overall medical activity of the Pulmonology Department and a reduction in the
      number of discharges from the hospital. There was a reduction in the number of
      admissions, and consequently in the need for beds in the Pulmonology Department.
      The complexity of the hospitalized patients increased, although the efficiency
      (standard functioning ratio) and quality (readmissions and mortality) of patient
      care remained stable. CONCLUSION: Day hospital pulmonology units are a useful
      tool in the management of respiratory patient care. They reduce the need for
      hospitalizations, while maintaining healthcare quality and complementing other
      care management instruments.

PMID- 23137779
TI  - Footprint ridge density: a new attribute for sexual dimorphism.
AB  - Estimation of sex of footprints can help in establishing the biological profile
      of potential suspects. This research attempts to study the sex differences in the
      ridge density in four different areas of a footprint. The study sample comprises
      footprints from both feet of 106 adult subjects from India that were analysed
      using standardized techniques. A total of 212 footprints were studied in detail.
      The four areas analysed in the study included the upper portion of the medial
      border of the great toe (F1), the ball of the great toe (F2), the ball of the 5th
      toe below the triradius point (F3) and the central prominent part of the heel
      (F4). Male-female differences in footprint ridge density were statistically
      analysed for each designated area and compared between right and left sides. The
      mean footprint ridge density was significantly higher among females than males in
      all designated areas (p<0.05) in both feet. No right-left differences were
      apparent in the analysed areas. Variations in footprint ridge density between
      different areas in right and left feet were evident among males and females. This
      study observes that sex differences exist in footprint ridge density among
      humans. Maximum sex differences were observed for ridge density in medial ball
      area, followed by great toe, lateral ball and minimum sex differences were
      observed in the heel region. It is observed that sex can be estimated from
      footprint ridge density with reasonable accuracy. The sexing potential of total
      footprint ridge density was 82.6% from the right and 83.6% from the left
      footprints respectively.

PMID- 23137780
TI  - Regulation of autophagy in cardiomyocytes by Ins(1,4,5)P(3) and IP(3)-receptors.
AB  - Autophagy is a process that removes damaged proteins and organelles and is of
      particular importance in terminally differentiated cells such as cardiomyocytes,
      where it has primarily a protective role. We investigated the involvement of
      inositol(1,4,5)trisphosphate (Ins(1,4,5)P(3)) and its receptors in autophagic
      responses in neonatal rat ventricular myocytes (NRVM). Treatment with the IP(3)
      receptor (IP(3)-R) antagonist 2-aminoethoxydiphenyl borate (2-APB) at 5 or 20
      MUmol/L resulted in an increase in autophagosome content, defined as puncta
      labeled by antibody to microtubule associated light chain 3 (LC3). 2-APB also
      increased autophagic flux, indicated by heightened LC3II accumulation, which was
      further enhanced by bafilomycin (10nmol/L). Expression of Ins(1,4,5)P(3) 5
      phosphatase (IP(3)-5-Pase) to deplete Ins(1,4,5)P(3) also increased LC3-labeled
      puncta and LC3II content, suggesting that Ins(1,4,5)P(3) inhibits autophagy. The
      IP(3)-R can act as an inhibitory scaffold sequestering the autophagic effector,
      beclin-1 to its ligand binding domain (LBD). Expression of GFP-IP(3)-R-LBD
      inhibited autophagic signaling and furthermore, beclin-1 co-immunoprecipitated
      with the IP(3)-R-LBD. A mutant GFP-IP(3)-R-LBD with reduced ability to bind
      Ins(1,4,5)P(3) bound beclin-1 and inhibited autophagy similarly to the wild type
      sequence. These data provide evidence that Ins(1,4,5)P(3) and IP(3)-R act as
      inhibitors of autophagic responses in cardiomyocytes. By suppressing autophagy,
      IP(3)-R may contribute to cardiac pathology.

PMID- 23137781
TI  - Cross-talk between glycogen synthase kinase 3beta (GSK3beta) and p38MAPK
      regulates myocyte enhancer factor 2 (MEF2) activity in skeletal and cardiac
      muscle.
AB  - Characterizing the signaling network that controls MEF2 transcription factors is
      crucial for understanding skeletal and cardiac muscle gene expression. Glycogen
      synthase kinase 3beta (GSK3beta) regulates MEF2 activity indirectly through
      reciprocal regulation of p38MAPK. Cross-talk between GSK3beta and p38MAPK
      regulates MEF2 activity in skeletal and cardiac muscle. Understanding cross-talk
      in the signaling network converging at MEF2 control has therapeutic implications
      in cardiac and skeletal muscle pathology. Glycogen synthase kinase 3beta
      (GSK3beta) is a known regulator of striated muscle gene expression suppressing
      both myogenesis and cardiomyocyte hypertrophy. Since myocyte enhancer factor 2
      (MEF2) proteins are key transcriptional regulators in both systems, we assessed
      whether MEF2 is a target for GSK3beta. Pharmacological inhibition of GSK3beta
      resulted in enhanced MEF2A/D expression and transcriptional activity in skeletal
      myoblasts and cardiac myocytes. Even though in silico analysis revealed GSK3beta
      consensus (S/T)XXX(S/T) sites on MEF2A, a subsequent in vitro kinase assay
      revealed that MEF2A is only a weak substrate. However, we did observe a
      posttranslational modification in MEF2A in skeletal myoblasts treated with a
      GSK3beta inhibitor which coincided with increased p38MAPK phosphorylation, a
      potent MEF2A activator, indicating that GSK3beta inhibition may de-repress
      p38MAPK. Heart specific excision of GSK3beta in mice also resulted in up
      regulation of p38MAPK activity. Interestingly, upon pharmacological p38MAPK
      inhibition (SB203580), GSK3beta inhibition loses its effect on MEF2
      transcriptional activity suggesting potent cross-talk between the two pathways.
      Thus we have documented that cross-talk between p38MAPK and GSK3beta signaling
      converges on MEF2 activity having potential consequences for therapeutic
      modulation of cardiac and skeletal muscle gene expression.

PMID- 23137782
TI  - Outreach and support in south London (OASIS), 2001-2011: ten years of early
      diagnosis and treatment for young individuals at high clinical risk for
      psychosis.
AB  - INTRODUCTION: Prevention of psychosis has become a major objective of modern
      clinical psychiatry. An increasing number of new services have been established
      in Europe and in the world. The OASIS team has become an established model where
      clinical practice and research are fully integrated in the field of preventative
      interventions in psychosis. METHOD: Comprehensive analysis of different clinical
      and service measures describing the 2001-2011 implementation of the OASIS team.
      RESULTS: Over the last decade, the OASIS team has received a total of 1102
      referrals, mostly young males from ethnic minorities. After the assessment, 35%
      were diagnosed with an At Risk Mental State (ARMS) while 32% were already
      psychotic. Within the ARMS, 70% met the inclusion criteria for the attenuated
      psychotic symptoms subgroup, 1% met the inclusion criteria for the genetic
      deterioration syndrome, 9% met inclusion criteria for a brief and self-limited
      intermittent psychotic episode and the others met inclusion criteria for more
      than one subgroup. Most of them had at least one comorbid diagnosis, mainly
      relating to anxiety and depressive domains. The majority of the OASIS clients
      received cognitive behavioural therapy alone or in combination with
      antidepressants/antipsychotics. Over the 2-year follow-up time, 44 subjects
      (15.2%) developed a frank psychotic episode. CONCLUSIONS: The OASIS service
      represents one of the largest and most established prodromal services in the
      world. The burden of research evidence and the translational impact produced on
      the clinical practice support the OASIS as a model for the development of similar
      services.

PMID- 23137783
TI  - Effects of sonication radiation on oil recovery by ultrasonic waves stimulated
      water-flooding.
AB  - Due to partial understanding of mechanisms involved in application of ultrasonic
      waves as enhanced oil recovery method, series of straight (normal), and
      ultrasonic stimulated water-flooding experiments were conducted on a long
      unconsolidated sand pack using ultrasonic transducers. Kerosene, vaseline, and
      SAE-10 (engine oil) were used as non-wet phase in the system. In addition, a
      series of fluid flow and temperature rise experiments were conducted using
      ultrasonic bath in order to enhance the understanding about contributing
      mechanisms. 3-16% increase in the recovery of water-flooding was observed.
      Emulsification, viscosity reduction, and cavitation were identified as
      contributing mechanisms. The findings of this study are expected to increase the
      insight to involving mechanisms which lead to improving the recovery of oil as a
      result of application of ultrasound waves.

PMID- 23137784
TI  - Cytokine phenotype, genotype, and renal outcomes at cardiac surgery.
AB  - BACKGROUND: Cardiac surgery modulates pro- and anti-inflammatory cytokine balance
      involving plasma tumour necrosis factor alpha (TNFalpha) and interleukin-10 (IL
      10) together with urinary transforming growth factor beta-1 (TGFbeta1),
      interleukin-1 receptor antagonist (IL1ra) and tumour necrosis factor soluble
      receptor-2 (TNFsr2). Effects on post-operative renal function are unclear. We
      investigated if following cardiac surgery there is a relationship between
      cytokine (a) phenotype and renal outcome; (b) genotype and phenotype and (c)
      genotype and renal outcome. Since angiotensin-2 (AG2), modulates TGFbeta1
      production, we determined whether angiotensin converting enzyme
      insertion/deletion (ACE I/D) genotype affects urinary TGFbeta1 phenotype as well
      as renal outcome. METHODS: In 408 elective cardiac surgery patients we measured
      pre- and 24 h post-operative urinary TGFbeta-1, IL1ra and TNFsr2 and pre- and 2 h
      post-operative plasma TNFalpha and IL-10. Post-operative responses were compared
      for each cytokine in patients grouped according to presence or absence of renal
      dysfunction defined as a drop from baseline eGFR of greater than 25% (as
      calculated by the method of modification of diet in renal disease (MDRD))
      occurring (1) within the first 24 and (2) 48 postoperative hours (early renal
      dysfunction), (3) on the fifth postoperative day (late renal dysfunction) or (4)
      at any time throughout the 5 day postoperative period (early and late combined).
      Patient genotype was determined for TNF/G-308A, TGFbeta1-509 C/T, IL10/G-1082A
      and ACE I/D. RESULTS: Post-operative plasma IL-10 and urinary TGFbeta1 responses
      were significantly higher in patients who developed early renal dysfunction.
      IL1ra and TNFsr2 responses were significantly lower 24h post-operatively in
      patients who developed late renal dysfunction. Genotype did not alter cytokine
      phenotype or outcome. CONCLUSIONS/INFERENCES: Cytokine profiling may help predict
      early and late renal dysfunction. Genotypes studied did not alter phenotype or
      outcome.

PMID- 23137786
TI  - Silk fibroin biomaterials for tissue regenerations.
AB  - Regeneration of tissues using cells, scaffolds and appropriate growth factors is
      a key approach in the treatments of tissue or organ failure. Silk protein fibroin
      can be effectively used as a scaffolding material in these treatments. Silk
      fibers are obtained from diverse sources such as spiders, silkworms, scorpions,
      mites and flies. Among them, silk of silkworms is a good source for the
      development of biomedical device. It possesses good biocompatibility, suitable
      mechanical properties and is produced in bulk in the textile sector. The unique
      combination of elasticity and strength along with mammalian cell compatibility
      makes silk fibroin an attractive material for tissue engineering. The present
      article discusses the processing of silk fibroin into different forms of
      biomaterials followed by their uses in regeneration of different tissues.
      Applications of silk for engineering of bone, vascular, neural, skin, cartilage,
      ligaments, tendons, cardiac, ocular, and bladder tissues are discussed. The
      advantages and limitations of silk systems as scaffolding materials in the
      context of biocompatibility, biodegradability and tissue specific requirements
      are also critically reviewed.

PMID- 23137785
TI  - Solution NMR studies of cell-penetrating peptides in model membrane systems.
AB  - Cell-penetrating peptides (CPPs) are a class of short, often cationic peptides
      that have the capability to translocate across cellular membranes, and although
      the translocation most likely involves several pathways, they interact directly
      with membranes, as well as with model bilayers. Most CPPs attain a three
      dimensional structure when interacting with bilayers, while they are more or less
      unstructured in aqueous solution. To understand the relationship between
      structure and the effect that CPPs have on membranes it is of great importance to
      investigate CPPs at atomic resolution in a suitable membrane model. Moreover, the
      location in bilayers is likely to be correlated with the translocation mechanism.
      Solution-state NMR offers a unique possibility to investigate structure, dynamics
      and location of proteins and peptides in bilayers. This review focuses on
      solution NMR as a tool for investigating CPP-lipid interactions. Structural
      propensities and cell-penetrating capabilities can be derived from a combination
      of CPP solution structures and studies of the effect that the peptides have on
      bilayers and the localization in a bilayer. 

PMID- 23137787
TI  - Risk counselling for family members in bipolar disorder and schizophrenia.
AB  - In bipolar disorder (BD) and schizophrenia (SZ) rare and de novo chromosomal
      microdeletions and microduplications (CNVs) have strong effects on risk. For de
      novo CNVs, the risk of BD or SZ is 10% and for deletions of the q11 region on
      chromosome 22, the risk of either of these disorders is 77%. A not-insignificant
      minority of BD and SZ patients have these types of event (4-6.5%).
      Psychotherapeutic intervention may be needed for within-family stigma and
      conflicts over genetic test results. These findings also raise ethical issues on
      stigma prevention, population screening, and abortion based on genotype.

PMID- 23137788
TI  - What e-patients want from the doctor-patient relationship: content analysis of
      posts on discussion boards.
AB  - BACKGROUND: People with long-term conditions are encouraged to take control and
      ownership of managing their condition. Interactions between health care staff and
      patients become partnerships with sharing of expertise. This has changed the
      doctor-patient relationship and the division of roles and responsibilities that
      traditionally existed, but what each party expects from the other may not always
      be clear. Information that people with long-term conditions share on Internet
      discussion boards can provide useful insights into their expectations of health
      care staff. This paper reports on a small study about the expectations that
      people with a long-term condition (diabetes) have of their doctors using
      information gleaned from Internet discussion boards. OBJECTIVE: The aim of this
      study was to ascertain what people with diabetes who use Internet discussion
      forums want from their doctors. The study objectives were to identify what people
      with diabetes (1) consider their role in condition management, (2) consider their
      doctor's role in managing their condition, (3) see as positive elements of their
      interactions with medical staff, and (4) find problematic in their interactions
      with medical staff. METHODS: The study used qualitative methodology to explore
      the experiences, views, and perceptions of individuals participating on 4
      Internet message boards. Posts made on the discussion boards were analyzed using
      the principles of qualitative content analysis. The meanings of sections of data
      were noted using codes that were developed inductively; those with similar codes
      were merged into subcategories and related subcategories were combined to form
      categories. RESULTS: The key themes identified in the study were ownership of
      condition management, power issues between people with long-term conditions and
      doctors, and ways in which people seek to manage their doctors. CONCLUSIONS:
      People with diabetes valued doctors who showed respect for them and their
      knowledge, and were willing to listen and openly discuss their options. Patients
      felt that they could and should take responsibility for and control of their day
      to-day disease management. They saw doctors as having a role in this process, but
      when this was lacking, many people felt able to use alternative means to achieve
      their goal, although the doctor's function in terms of gatekeeping resources
      could create difficulties for them in this respect.

PMID- 23137789
TI  - Successful clearance of human parainfluenza virus type 2 viraemia with
      intravenous ribavirin and immunoglobulin in a patient with acute myocarditis.
AB  - Human parainfluenza virus (HPIV) infection as an aetiology of acute viral
      myocarditis is rare, with only few cases reported in the literature to date. Here
      we report a case of fulminant HPIV-2 myocarditis in a 47 year-old man with
      viraemia who was successfully treated with intravenous ribavirin and intravenous
      immunoglobulin (IVIG). There are currently no recommendations on the treatment of
      HPIV myocarditis. We are, to our knowledge, the first to report a patient with a
      documented HPIV-2 viraemia that subsequently cleared after the initiation of
      antiviral therapy. Although it is difficult to definitively attribute the
      patient's clinical improvement to ribavirin or IVIG alone, our case does suggest
      that clinicians may wish to consider initiating ribavirin and IVIG in patients
      with HPIV myocarditis and persistent viraemia not responding to supportive
      measures alone.

PMID- 23137790
TI  - Type II heat-labile enterotoxins: structure, function, and immunomodulatory
      properties.
AB  - The heat-labile enterotoxins (HLTs) of Escherichia coli and Vibrio cholerae are
      classified into two major types on the basis of genetic, biochemical, and
      immunological properties. Type I and Type II HLT have been intensively studied
      for their exceptionally strong adjuvant activities. Despite general structural
      similarities, these molecules, in intact or derivative (non-toxic) forms, display
      notable differences in their mode of immunomodulatory action. The molecular basis
      of these differences has remained largely uncharacterized until recently. This
      review focuses on the Type II HLTs and their immunomodulatory properties which
      depend largely on interactions with unique gangliosides and Toll-like receptors
      that are not utilized by the Type I HLTs.

PMID- 23137791
TI  - Gender-specific combined effects of smoking and hypertension on cardiovascular
      disease mortality in elderly Koreans: THe Kangwha Cohort Study.
AB  - OBJECTIVE: We examined gender-specific combined effects of smoking and
      hypertension on risk of mortality from cardiovascular disease in elderly Korean
      men and women. STUDY DESIGN: This study followed a cohort of 6097 residents (2593
      men, 3504 women) in the general population of Kangwha County, aged >=55 years in
      March 1985 and examined their cause-specific mortality for 20.8 years, up to
      December 31, 2005. All participants were followed up more than once after the
      1985 survey. MAIN OUTCOME MEASURES: We calculated hazard ratios for mortality for
      the combined sets of smoking habits and blood pressure levels using the Cox
      proportional-hazard model. The set of non-smokers with normal blood pressure
      served as a reference group. RESULTS: During the 20.8 years of follow-up, 759
      people died from cardiovascular disease. The risk of mortality from
      cardiovascular disease and stroke according to smoking or hypertension was not
      different between men and women. However, the risk among smokers combined with
      hypertension was higher in men than in women; the multivariable-adjusted hazard
      ratios (95% CI) for mortality from cardiovascular disease and stroke were 4.52
      (1.67-12.21) and 6.37 (1.57-25.85) in men and 2.11 (1.37-3.24) and 2.41 (1.44
      4.01) in women, respectively. CONCLUSIONS: The magnitude of the joint effects of
      smoking and hypertension on cardiovascular disease and stroke mortality was
      different between men and women. This study suggests that combining quitting
      smoking with lowering blood pressure could contribute to preventing
      cardiovascular disease and stroke, especially in men.

PMID- 23137792
TI  - Angiographic embolization of large duodenal varix in a cirrhotic patient.

PMID- 23137793
TI  - Spontaneous rupture of aneurysm of the right colic artery.

PMID- 23137794
TI  - Obscure hemosuccus pancreaticus due to dorsal pancreatic arteriorrhexis.

PMID- 23137795
TI  - Response to exercise in patients with liver cirrhosis: implications for liver
      transplantation.
AB  - End-stage liver cirrhosis is a systemic disease carrying a short-term desperate
      prognosis without liver transplantation. Given the discrepancy between the
      growing number of candidates and the limited available liver grafts, the pre
      transplantation screening process has become a challenging task. Cardiopulmonary
      exercise testing, by measuring maximal oxygen consumption at peak exercise,
      provides a global integrative approach of the health status of an individual. In
      the setting of liver cirrhosis, decreased oxygen consumption at peak exercise may
      result from a combination of multiple extra-hepatic complications, including
      deconditioning, malnutrition-associated muscle weakness, anaemia, cirrhotic
      cardiomyopathy, and hepato-pulmonary syndrome for instance. In addition, oxygen
      consumption at peak exercise not only correlated with the severity of the liver
      disease, but it is also independently associated with survival following liver
      transplantation. The present article aims to review the numerous determinants of
      impaired aerobic capacity in patients with severe liver disease, and to discuss
      how useful is cardiopulmonary exercise testing as a critical tool in the pre
      transplantation assessment of these patients.

PMID- 23137796
TI  - The binding of multiple nuclear receptors to a single regulatory region is
      important for the proper expression of EDG84A in Drosophila melanogaster.
AB  - Nuclear receptor transcription factor family members share target sequence
      similarity; however, little is known about how these factors exert their specific
      regulatory control. Here, we examine the mechanism regulating the expression of
      the Drosophila EDG84A gene, a target gene of the orphan nuclear receptor betaFTZ
      F1, as a model to study the cooperative behavior among nuclear receptors. We show
      that the three nuclear receptors betaFTZ-F1, DHR3, and DHR39 bind to a common
      element in the EDG84A promoter. The expression level of the EDG84A promoter-lacZ
      reporter genes in DHR39-induced and mutant animals, respectively, suggests that
      DHR39 works as a repressor. The activity of a reporter gene carrying a mutation
      preventing DHR3 binding was reduced in ftz-f1 mutants and rescued by the induced
      expression of betaFTZ-F1, suggesting that DHR3 and betaFTZ-F1 activate the EDG84A
      gene in a redundant manner. A reporter gene carrying a mutation that abolishes
      DHR39 and FTZ-F1 binding was prematurely expressed, and the expression level of
      the reporter gene carrying a mutation preventing DHR3 binding was reduced. These
      findings suggest that the temporal expression of this gene is mainly controlled
      by betaFTZ-F1 but that the binding of DHR3 is also important. Comparison of the
      binding site sequence among Drosophila species suggests that DHR3 binding ability
      was gained after the melanogaster subgroup evolved, and this ability may
      contribute to the robust expression of this gene. These results show the
      complicated regulatory mechanisms utilized by multiple nuclear receptors to
      properly regulate the expression of their target gene through a single target
      site.

PMID- 23137797
TI  - Analysis of the structure and conformational states of DewA gives insight into
      the assembly of the fungal hydrophobins.
AB  - The hydrophobin DewA from the fungus Aspergillus nidulans is a highly surface
      active protein that spontaneously self-assembles into amphipathic monolayers at
      hydrophobic:hydrophilic interfaces. These monolayers are composed of fibrils that
      are a form of functional amyloid. While there has been significant interest in
      the use of DewA for a variety of surface coatings and as an emulsifier in
      biotechnological applications, little is understood about the structure of the
      protein or the mechanism of self-assembly. We have solved the solution NMR
      structure of DewA. While the pattern of four disulfide bonds that is a defining
      feature of hydrophobins is conserved, the arrangement and composition of
      secondary-structure elements in DewA are quite different to what has been
      observed in other hydrophobin structures. In addition, we demonstrate that DewA
      populates two conformations in solution, both of which are assembly competent.
      One conformer forms a dimer at high concentrations, but this dimer is off-pathway
      to fibril formation and may represent an assembly control mechanism. These data
      highlight the structural differences between fibril-forming hydrophobins and
      those that form amorphous monolayers. This work will open up new opportunities
      for the engineering of hydrophobins with novel biotechnological applications.

PMID- 23137798
TI  - Deployment-related injury and posttraumatic stress disorder in US military
      personnel.
AB  - BACKGROUND: The current military conflicts in Iraq and Afghanistan have resulted
      in the most US casualties since the Vietnam War. Previous research on the
      association between deployment-related injury and posttraumatic stress disorder
      (PTSD) has yielded mixed results. OBJECTIVES: To examine the effect of battle
      injury (BI) relative to non-battle injury (NBI) on the manifestation of PTSD
      symptoms in military personnel and to assess the demographic, injury-specific,
      and pre-injury factors associated with PTSD following a BI. PATIENTS AND METHODS:
      A total of 3403 personnel with deployment-related injury (1777 BI and 1626 NBI)
      were identified from the Expeditionary Medical Encounter Database. Records were
      electronically matched to Post-Deployment Health Assessment (PDHA) data completed
      1-6 months post-injury. The PTSD screening outcome was identified using a four
      item screening tool on the PDHA. RESULTS: Compared to those with NBI, personnel
      with BI had more severe injuries, reported higher levels of combat exposure, and
      had higher rates of positive PTSD screen. After adjusting for covariates,
      personnel with BI were twice as likely to screen positive for PTSD compared to
      those with NBI (odds ratio [OR], 2.10; 95% confidence interval [CI], 1.60-2.75).
      In multivariable analysis among battle-injured personnel only, moderate and
      serious-severe injury (OR, 1.49; 95% CI, 1.12-2.00 and OR, 1.64; 95% CI, 1.01
      2.68, respectively), previous mental health diagnosis within 1 year of deployment
      (OR, 2.69; 95% CI, 1.50-4.81), and previous BI (OR, 1.96; 95% CI, 1.22-3.16)
      predicted a positive PTSD screen. CONCLUSIONS: Military personnel with BI have
      increased odds of positive PTSD screen following combat deployment compared to
      those with NBI. Post-deployment health questionnaires may benefit from questions
      that specifically address whether service members experienced an injury during
      combat.

PMID- 23137799
TI  - Splenic artery embolisation in children and adolescents--an 8 year experience.
AB  - BACKGROUND: Non-operative management (NOM) is the treatment of choice in blunt
      splenic injuries in the paediatric population, with reported success rates
      exceeding 90%. Splenic artery embolisation (SAE) was added to our institutional
      treatment protocol for splenic injury in 2002. We wanted to review indications
      for SAE and the clinical outcome of splenic injury management in children
      admitted between August 1, 2002 and July 31, 2010. METHODS: Patients aged <17
      years with splenic injury were identified in the institutional trauma and medical
      code registries. Patient charts and computed tomographic (CT) scans were
      reviewed. RESULTS: Of the 72 children and adolescents with splenic injury
      included during the 8 year study period, 66 patients (92%) were treated non
      operatively and six underwent operative management. Severe splenic injury (OIS
      grade 3-5) was diagnosed in 67 patients (93%). SAE was performed in 22 of the NOM
      patients. Indications for SAE included - bleeding (n=8), pseudoaneurysms (n=2),
      contrast extravasation (n=2), high OIS injury grade (n=8) and prophylactic due to
      specific disease (n=2). NOM was successful in all but one case (98%). For the
      patients aged <= 14 years, extravasation on initial CT scan correlated to delayed
      bleeding (p<0.001). Two SAE procedure specific complications were registered, but
      resolved without significant sequelae. CONCLUSION: After SAE was added to the
      institutional treatment protocol, 22 of 66 NOM paediatric patients underwent SAE.
      NOM was successful in 98% and a 90% splenic preservation rate was achieved.
      Contrast extravasation correlated to delayed splenic bleeding in children <= 14
      years.

PMID- 23137800
TI  - Altered auditory processing in frontal and left temporal cortex in 22q11.2
      deletion syndrome: a group at high genetic risk for schizophrenia.
AB  - In order to investigate electroencephalographic (EEG) biomarkers of auditory
      processing for schizophrenia, we studied a group with a well known high-risk
      profile: patients with 22q11.2 deletion syndrome (22q11 DS) have a 30% risk of
      developing schizophrenia during adulthood. We performed high-density EEG source
      imaging to measure auditory gating of the P50 component of the evoked potential
      and middle to late latency auditory processing in 21 participants with the
      22q11.2 deletion and 17 age-matched healthy controls. While we found no
      indication of altered P50 suppression in 22q11 DS, we observed marked differences
      for the first N1 component with increased amplitudes on central electrodes,
      corresponding to increased activations in dorsal anterior cingulate and medial
      frontal cortex. We also found a left lateralized reduction of activation of
      primary and secondary auditory cortex during the second N1 (120ms) and the P2
      component in 22q11 DS. Our results show that sensory gating and activations until
      50ms were preserved in 22q11 DS, while impairments appear at latencies that
      correspond to higher order auditory processing. While the increased activation of
      cingulate and medial frontal cortex could reflect developmental changes in 22q11
      DS, the reduced activity seen in left auditory cortex might serve as a biomarker
      for the development of schizophrenia, if confirmed by longitudinal research
      protocols.

PMID- 23137801
TI  - Nonlinear relationships between anxiety and visual processing of own and others'
      faces in body dysmorphic disorder.
AB  - Individuals with body dysmorphic disorder (BDD) often experience anxiety, as well
      as perceptual distortions of appearance. Anxiety has previously been found to
      impact visual processing. This study therefore tested the relationship between
      anxiety and visual processing of faces in BDD. Medication-free participants with
      BDD (N=17) and healthy controls (N=16) viewed photographs of their face and a
      familiar face during functional magnetic resonance imaging. Blood-oxygen-level
      dependent signal changes in regions involved in anxiety (amygdala) and detailed
      visual processing (ventral visual stream-VVS) were regressed on anxiety scores.
      Significant linear relationships between activity in the amygdala and VVS were
      found in both healthy controls and individuals with BDD. There was a trend of a
      quadratic relationship between anxiety and activity in the right VVS and a linear
      relationship between anxiety and activity in the left VVS for the BDD sample, and
      this was stronger for own-face stimuli versus familiar-face. Results suggest that
      anxiety symptoms in BDD may be associated with activity in systems responsible
      for detailed visual processing. This may have clinical implications related to
      heightened perceptual distortions associated with anxiety.

PMID- 23137802
TI  - Brain activation and heart rate during script-driven traumatic imagery in PTSD:
      preliminary findings.
AB  - Patients with posttraumatic stress disorder (PTSD) experience psychological and
      physiological distress. However, imaging research has mostly focused on the
      psychological aspects of the disorder. Considered an expression of distress,
      heart rate (HR) in PTSD is often elevated. In the current study, we sought to
      identify brain regions associated with increased HR in PTSD. Nine patients with
      PTSD and six healthy trauma survivors were scanned while resting, clenching
      teeth, and listening to neutral and traumatic scripts. Brain function was
      evaluated using H2O15 positron emission tomography (PET). HR was monitored by
      electrocardiogram. Data were analyzed using statistical parametric mapping (SPM).
      Subjects with PTSD exhibited a significant increase in HR upon exposure to
      traumatic scripts, while trauma survivors did not. Correlations between regional
      cerebral blood flow and HR were found only in patients with PTSD, in
      orbitofrontal, precentral and occipital regions. Neither group showed correlation
      between rCBF and HR in the amygdala or hippocampus. These preliminary results
      indicate that "top down" central nervous system regulation of autonomic stress
      response in PTSD may involve associative, sensory and motor areas in addition to
      regions commonly implicated in fear conditioning.

PMID- 23137804
TI  - Magnetic resonance spectroscopy reveals N-acetylaspartate reduction in
      hippocampus and cingulate cortex after fear conditioning.
AB  - The fear conditioning in rodents provides a valuable translational tool to
      investigate the neural basis of learning and memory and potentially the
      neurobiology of post-traumatic stress disorder (PTSD). Neurobiological changes
      induced by fear conditioning have largely been examined ex vivo while progressive
      'real-time' changes in vivo remain under-explored. Single voxel proton magnetic
      resonance spectroscopy (1H MRS) of the hippocampus, cingulate cortex and thalamus
      of adult male C57BL/6N mice (N=12) was performed at 1 day before, 1 day and 1
      week after, fear conditioning training using a 7T scanner. N-acetylaspartate
      (NAA), a marker for neuronal integrity and viability, significantly decreased in
      the hippocampus at 1 day and 1 week post-conditioning. Significant NAA reduction
      was also observed in the cingulate cortex at 1 day post-conditioning. These
      findings of hippocampal NAA decrease indicate reduced neuronal dysfunction and/or
      neuronal integrity, contributing to the trauma-related PTSD-like symptoms. The
      neurochemical changes characterized by 1H MRS can shed light on the biochemical
      mechanisms of learning and memory. Moreover, such information can potentially
      facilitate prompt intervention for patients with psychiatric disorders.

PMID- 23137803
TI  - Striatal-limbic activation is associated with intensity of anticipatory anxiety.
AB  - Anxiety experienced in anticipation of impending aversive events induces striatal
      limbic activation. However, previous functional magnetic imaging (fMRI) studies
      of anticipatory anxiety have utilized post-test measures of anxiety, making a
      direct association between neural activation and distress problematic. This
      paradigm was designed to assess the blood-oxygen-level-dependent (BOLD) response
      to an aversive conditioned stimulus while simultaneously measuring subjective
      anxiety. Fifteen male healthy subjects (45.5+/-8.5 years old) were studied. A
      high-threat conditioned stimulus (CS) was paired with either an unpredictable,
      highly aversive (painful) or non-aversive (non-painful) unconditioned stimulus
      and compared to a low-threat CS paired with a predictable, non-aversive stimulus.
      Neural response was assessed with fMRI, and subjective anxiety (1-4) was recorded
      upon the presentation of each CS. High subjective ratings of real-time
      anticipatory anxiety (2-4), relative to low anticipatory anxiety (1), elicited
      increased activation in the bilateral striatum, bilateral orbital frontal cortex,
      left anterior insula, and anterior cingulate cortex (ACC) and decreased
      activation in the posterior cingulate cortex (PCC). The amplitude of BOLD signal
      change generally paralleled the subjective rating of anxiety. Real-time measures
      of anticipatory anxiety confirm previous reports, using post-test measures of
      anxiety, of striatal-limbic activation during anticipatory anxiety while
      simultaneously demonstrating an increase in BOLD response in parallel with
      heightened anxiety.

PMID- 23137805
TI  - Nicotine effects on anterior cingulate cortex in schizophrenia and healthy
      smokers as revealed by EEG-informed fMRI.
AB  - Nicotine can have beneficial effects on attention performance and corresponding
      brain function in both schizophrenia patients and healthy controls, but it
      remains controversial whether nicotine affects brain function differentially in
      patients vs. controls. The effects of nicotine on brain activity elicited by
      attention-requiring oddball-type tasks have not been studied in schizophrenia
      patients. In this study we sought to investigate the impact of nicotine on the
      p300 evoked potential component and corresponding fMRI (functional magnetic
      resonance imaging) activation measures in schizophrenia patients and controls.
      Applying a double-blind, placebo-controlled cross-over design, the effects of 1mg
      nasal nicotine on brain activity elicited by a visual oddball-type task in N=14
      schizophrenia and N=15 control smokers were studied with simultaneous EEG-fMRI.
      EEG single trial amplitudes were used to inform the fMRI analysis. We found a
      nicotine-associated increase in P300-informed fMRI activation in schizophrenia
      patients and controls, mainly in the anterior cingulate and adjacent medial
      frontal cortex. No group differences in the response to nicotine were found.
      Remarkably, averaged EEG and fMRI activation measures considered in isolation
      were largely unaffected by nicotine. Taken together, the effects of nicotine on
      P300 amplitude-associated brain activation do not seem to be fundamentally
      different in schizophrenic smokers and healthy controls.

PMID- 23137806
TI  - Trait aggression and trait impulsivity are not related to frontal cortex 5-HT2A
      receptor binding in healthy individuals.
AB  - Numerous studies indicate that the serotonergic (5-HT) transmitter system is
      involved in the regulation of impulsive aggression and there is from post-mortem,
      in vivo imaging and genetic studies evidence that the 5-HT2A receptor may be
      involved. We investigated 94 healthy individuals (60 men, mean age 47.0+/-18.7,
      range 23-86) to determine if trait aggression and trait impulsivity were related
      to frontal cortex 5-HT2A receptor binding (5-HT2AR) as measured with [18F]
      altanserin PET imaging. Trait aggression and trait impulsivity were assessed with
      the Buss-Perry Aggression Questionnaire (AQ) and the Barratt Impulsiveness Scale
      11 (BIS-11). Statistical analyses were conducted using a multiple linear
      regression model and internal consistency reliability of the AQ and BIS-11 was
      evaluated by Cronbach's alpha. Contrary to our hypothesis, results revealed no
      significant associations between 5-HT2AR and the AQ or BIS-11 total scores. Also,
      there was no significant interaction between gender and frontal cortex 5-HT2AR in
      predicting trait aggression and trait impulsivity. This is the first study to
      examine how 5-HT2AR relates to trait aggression and trait impulsivity in a large
      sample of healthy individuals. Our findings are not supportive of a selective
      role for 5-HT2AR in mediating the 5-HT related effects on aggression and
      impulsivity in psychiatrically healthy individuals.

PMID- 23137807
TI  - Effects of video game playing on cerebral blood flow in young adults: a SPECT
      study.
AB  - To study the impact of video game playing on the human brain, the effects of two
      video games playing on cerebral blood flow (CBF) in young adults were determined.
      Thirty healthy subjects comprising 18 males and 12 females who were familiar with
      video game playing were recruited. Each subject underwent three sessions of
      single photon emission computed tomography (SPECT) with a bolus injection of 20
      mCi (99m)Tc ECD IV to measure their CBF. The first measurement was performed as
      baseline, the second and third measurements were performed after playing two
      different video games for 30 min, respectively. Statistic parametric mapping
      (SPM2) with Matlab 6.5 implemented on a personal computer was used for image
      analysis. CBF was significantly decreased in the prefrontal cortex and
      significantly increased in the temporal and occipital cortices after both video
      games playing. Furthermore, decreased CBF in the anterior cingulate cortex (ACC)
      which was significantly correlated with the number of killed characters was found
      after the violent game playing. The major finding of hypo-perfusion in prefrontal
      regions after video game playing is consistent with a previous study showing
      reduced or abnormal prefrontal cortex functions after video game playing. The
      second finding of decreased CBF in the ACC after playing the violent video game
      provides support for a previous hypothesis that the ACC might play a role in
      regulating violent behavior.

PMID- 23137808
TI  - Hyperfrontality and hypoconnectivity during refreshing in schizophrenia.
AB  - Anomalous activations of the prefrontal cortex (PFC) and posterior cerebral areas
      have been reported in previous studies of working memory in schizophrenia.
      Several interpretations have been reported: e.g., neural inefficiency, the use of
      different strategies and differences in the functional organization of the
      cerebral cortex. To better understand these abnormal activations, we investigated
      the cerebral bases of a working memory component process, namely refreshing
      (i.e., thinking briefly of a just-activated representation). Fifteen patients
      with schizophrenia and 15 control subjects participated in this functional
      magnetic resonance imaging (fMRI) study. Participants were told that whenever
      they saw a word on the screen, they had to read it silently to themselves (read
      and repeat conditions), and when they saw a dot, they had to think of the just
      previous word (refresh condition). The refresh condition (in comparison with the
      read condition) was associated with significantly increased activation in the
      left inferior frontal gyrus and significantly decreased connectivity within the
      prefrontal cortex and between the prefrontal and parietal cortices in patients
      with schizophrenia in comparison with control subjects. These results suggest
      that prefrontal dysfunctions in schizophrenia might be related to a defective
      ability to initiate (rather than to execute) specific cognitive processes.

PMID- 23137809
TI  - DDB1 is a cellular substrate of NS3/4A protease and required for hepatitis C
      virus replication.
AB  - Hepatitis C virus (HCV) infection often causes long-term persistent hepatitis,
      which eventually leads to liver cirrhosis and hepatocellular carcinoma. HCV
      encoded NS3/4A protease plays an important role in HCV immune evasion by cleaving
      key adapter proteins VISA and TRIF of the RIG-I-like receptors and Toll-like
      receptors mediated interferon (IFN) induction pathways. To further understand the
      roles of NS3/4A in HCV life cycle, we identified DDB1 as a cellular substrate of
      NS3/4A protease by biochemical purification and mass spectrometry analysis.
      NS3/4A interacted with DDB1 and cleaved DDB1 in HCV-infected cells. Mutagenesis
      indicated that NS3/4A cleaved DDB1 at the residue of C378. Overexpression of DDB1
      potentiated HCV replication, whereas knockdown of DDB1 dramatically inhibited HCV
      replication. Furthermore, our data indicated that the cleavage of DDB1 by NS3/4A
      protease was required for HCV replication. Our findings suggest that DDB1 is a
      cellular substrate of NS3/4A required for HCV replication and provide new insight
      into the interaction between HCV and host cells.

PMID- 23137810
TI  - Endoplasmic reticulum export and vesicle formation of the movement protein of
      Chinese wheat mosaic virus are regulated by two transmembrane domains and depend
      on the secretory pathway.
AB  - The 37K protein of Chinese wheat mosaic virus (CWMV) belongs to the 30K
      superfamily of plant virus movement proteins. CWMV 37K trans-complemented the
      cell-to-cell spread of a movement-defective Potato virus X. CWMV 37K fused to
      enhanced green fluorescent protein localized to plasmodesmata and formed
      endoplasmic reticulum (ER)-derived vesicular and large aggregate structures. CWMV
      37K has two putative N-terminal transmembrane domains (TMDs). Mutations
      disrupting TMD1 or TMD2 impaired 37K movement function; those mutants were unable
      to form ER-derived structures but instead accumulated in the ER. Treatment with
      Brefeldin A or overexpression of the dominant negative mutant of Sar1 retained
      37K in the ER, indicating that ER export of 37K is dependent on the secretory
      pathway. Moreover, CWMV 37K interacted with pectin methylesterases and mutations
      in TMD1 or TMD2 impaired this interaction in planta. The results suggest that the
      two TMDs regulate the movement function and intracellular transport of 37K.

PMID- 23137811
TI  - Old and new criteria for the classification and diagnosis of fibromyalgia:
      comparison and evaluation.

PMID- 23137812
TI  - Brewers' spent grain; bioactivity of phenolic component, its role in animal
      nutrition and potential for incorporation in functional foods: a review.
AB  - Brewers' spent grain (BSG) is a low-value co-product of the brewing industry
      produced in large quantities annually. This paper reviews the existing evidence
      regarding the phenolic component of BSG, focusing on composition, extraction and
      biofunctions such as antioxidant, anti-atherogenic, anti-inflammatory and anti
      carcinogenic activities. Furthermore, the incorporation of BSG in foodstuffs will
      be discussed, including the use of BSG as an animal feed supplement and the
      potential of BSG to be incorporated into foods for human consumption. BSG
      contains hydroxycinnamic acids including ferulic acid, p-coumaric acid and
      caffeic acid; which have shown bioactivity in the pure form (antioxidant, anti
      inflammatory, anti-atherogenic and anti-cancer). Phenolic extracts from BSG have
      also shown antioxidant potential, by protecting against oxidant-induced DNA
      damage, possibly by Fe chelation. Studies show that BSG has many benefits when
      used as a supplement in animal feed, such as increasing milk yield, milkfat
      content and in providing essential dietary amino acids. The incorporation of BSG
      in human foods such as cookies and ready-to-eat snacks has resulted in increased
      protein and fibre contents of the products, where the changes in organoleptic
      properties are controllable. It can be concluded that the phenolic component of
      BSG has potential bioactive effects, which are worth pursuing given that the
      inclusion of BSG into human foodstuffs is viable and beneficial.

PMID- 23137813
TI  - Tumor thrombosis detected on PET/CT scanning in a patient with metastasic
      melanoma.

PMID- 23137814
TI  - Measurement of chromogranin A in porcine saliva: validation of a time-resolved
      immunofluorometric assay and evaluation of its application as a marker of acute
      stress.
AB  - The objective of this study was to develop and validate a time-resolved
      immunofluorometric assay (TR-IFMA) for porcine salivary chromogranin A (CgA)
      measurements, using a species-specific antibody, and evaluate its behaviour in an
      acute stress model. Polyclonal antibodies were produced in rabbits immunized with
      a synthetic porcine fragment of CgA359-379 and used to develop a sandwich TR
      IFMA. This TR-IFMA was analytically validated and showed intra- and inter-assay
      coefficients of variation of 6.23% and 5.82%, respectively, an analytical limit
      of detection of 4.27 * 10-3 MUg/ml and a limit of quantification of 24.5 * 10-3
      MUg/ml. The assay also demonstrated a high level of accuracy, as determined by
      linearity under dilution (r = 0.975) and recovery tests. When a model of
      experimental acute stress, in which animals were immobilized for 3 min with a
      nose snare (stressor stimulus), was applied, a significant increase (P < 0.05) in
      CgA levels in saliva was detected at 15 min post-stressor stimulus. These results
      indicate that the assay developed in this study could measure CgA in porcine
      saliva in a reliable way and that the concentrations of CgA in saliva samples of
      pigs increase after an acute stress situation.

PMID- 23137815
TI  - Distribution and characterization of doublecortin-expressing cells and fibers in
      the brain of the adult pigeon (Columba livia).
AB  - Doublecortin (DCX) is a microtubule-associated protein essential for the
      migration of immature neurons in the developing and adult vertebrate brain.
      Herein, the distribution of DCX-immunoreactive (DCX-ir) cells in the
      prosencephalon of the adult pigeon (Columba livia) is described, in order to
      collect the evidence of their immature neural phenotype and to investigate their
      putative place of origin. Bipolar and multipolar DCX-ir cells were observed to be
      widespread throughout the parenchyma of the adult pigeon forebrain. Small,
      bipolar and fusiform DCX-ir cells were especially concentrated at the tips of the
      lateral walls of the lateral ventricles (VZ) and sparsely distributed in the
      remaining ependyma. Multipolar DCX-ir cells populated the pallial regions. None
      of these DCX-ir cells seemed to co-express NeuN or GFAP, suggesting that they
      were immature neurons. Two different migratory-like routes of DCX-ir cells from
      the VZ toward different targets in the parenchyma were putatively identified: (i)
      rostral migratory-like bundle; and (ii) lateral migratory-like bundle. In
      addition, pial surface bundles and intra-ependymal fascicles were also observed.
      Pigeons treated with 5-bromo-desoxyuridine (BrdU, 3 intraperitoneal injections of
      100mg/kg 2h apart, sacrificed 2h after last injection) displayed BrdU
      immunoreactive cells (BrdU-ir) in VZ and ependyma whereas the parenchyma was free
      of such cells. Despite the regional overlapping, there was no evidence of double
      labeling between BrdU and DCX. Therefore, the VZ in the brain of adult pigeons
      seems to have rapidly dividing cells as putative progenitors of newborn neurons
      populating the forebrain. The distribution of the newborn neurons in the avian
      prosencephalon and their migration pathways appear to be larger than in mammals,
      suggesting that the morphological turnover of forebrain circuits is an important
      mechanism for brain plasticity in avian species during adulthood.

PMID- 23137816
TI  - "Limbic associative" and "autonomic" amygdala in teleosts: a review of the
      evidence.
AB  - The amygdaloid nuclei form an important hub of structures associated with diverse
      aspects of cognition and emotional behavior. Homologous structures have been
      determined in tetrapods, but homology of amygdala-like regions in bony fishes is
      presently unclear. Based on connectivity patterns, genoarchitecture, chemical
      neuroanatomy, and functional studies, we suggest that the dorsomedial portion of
      the pallium of Actinopterygii is the homolog of the basolateral/lateral amygdala
      ("frontotemporal amygdaloid system"), while the supracommissural and
      postcommissural portions of the subpallium are homologous to the extended central
      amygdala (central amygdaloid nucleus and bed nucleus of the stria terminalis).
      Nonetheless, the differentiation between these nuclei is not as clear-cut as in
      mammals, and there is no clear evidence for the existence of an "olfactory"
      medial amygdala in Actinopterygii, suggesting that the parcellation of one or two
      amygdaloid nuclei into many subnuclei occurred with the appearance of a true
      vomeronasal system.

PMID- 23137817
TI  - The impact of BVDV infection on adaptive immunity.
AB  - Bovine viral diarrhea virus (BVDV) causes immunosuppression of the adaptive
      immune response. The level of suppression of the adaptive immune response is
      strain dependent. The early events of antigen presentation require activation of
      toll-like receptors that results in the release of pro-inflammatory cytokines.
      Non-cytopathic (ncp) BVDV infection stimulates cytokines from macrophages in
      vitro but the effect of BVDV infection in vivo on macrophages or in vitro with
      monocytes is not clear. Antigen presentation is decreased and co-stimulatory
      molecules are down regulated. T-lymphocytes numbers are reduced following BVDV
      infection in a strain dependent manner. There is recruitment of lymphocytes to
      the bronchial alveolar space following cytopathic (cp) BVDV infection. Depletion
      of T-lymphocytes occurs in the lymphoid tissue and is strain dependent. BVDV cp T
      lymphocyte responses appear to be primarily a T helper 1 response while the
      response following ncp BVDV induces a T helper 2 response. Cytotoxic T
      lymphocytes (CTL), an important BVDV defense mechanism are compromised. The major
      neutralizing antigens are well characterized but cross-protection between strains
      is variable. PI animals have normal adaptive immune responses with the exception
      of the PI strain immunotolerance and mucosal disease may be a function of the
      level of gamma delta T cells.

PMID- 23137818
TI  - Ability of ELISA and a toxin neutralization assay to detect changes in
      immunogenicity of a recombinant Bacillus anthracis protective antigen vaccine
      upon storage.
AB  - We examined the capability of a mouse immunogenicity assay to detect improper
      storage of a recombinant protective antigen (rPA)-based anthrax vaccine
      formulated with an aluminum adjuvant, using ELISA and a toxin neutralization
      assay (TNA) to measure the antibody response to rPA. The vaccine was stored at 4 
      degrees C, room temperature (RT) or 37  degrees C for one, four and eight weeks
      and used for immunization, along with freshly prepared vaccine. Results showed
      that, contrary to ELISA, TNA is suitable to detect a loss of immunogenicity of
      the rPA vaccine following its exposure to RT for a period of eight weeks and to
      37  degrees C for a period as short as 1 week.

PMID- 23137819
TI  - Stop the silent misdiagnosis: patients' preferences matter.

PMID- 23137820
TI  - Risks of adverse pregnancy and birth outcomes in women treated or not treated
      with mood stabilisers for bipolar disorder: population based cohort study.
AB  - OBJECTIVE: To investigate the risks of adverse pregnancy and birth outcomes for
      treated and untreated bipolar disorder during pregnancy. DESIGN: Population based
      cohort study using data from national health registers. SETTING: Sweden.
      PARTICIPANTS: 332,137 women with a last menstrual period anytime after 1 July
      2005 and giving birth anytime before the end of 31 December 2009. Women with a
      record of at least two bipolar diagnoses were identified and grouped as treated
      (n = 320)-those who had filled a prescription for mood stabilisers (lithium,
      antipsychotics, or anticonvulsants) during pregnancy-or untreated (n = 554). Both
      groups were compared with all other women giving birth (n = 331,263). MAIN
      OUTCOME MEASURES: Preterm birth, mode of labour initiation, gestational diabetes,
      infants born small or large for gestational age, neonatal morbidity, and
      congenital malformations. RESULTS: Of the untreated women, 30.9% (n = 171) were
      induced or had a planned caesarean delivery compared with 20.7% (n = 68,533)
      without bipolar disorder (odds ratio 1.57, 95% confidence interval 1.30 to 1.90).
      The corresponding values for the treated women were 37.5% (n = 120) (2.12, 1.68
      to 2.67). The risks of preterm birth in both treated and untreated women were
      increased by 50%. Of the untreated women, 3.9% (n = 542) had a microcephalic
      infant compared with 2.3% (324,844) of the women without bipolar disorder (1.68,
      1.07 to 2.62). The corresponding values for the treated women were 3.3% (n = 311)
      (1.26, 0.67 to 2.37). Similar trends were observed for risks of infants being
      small for gestational age infants for weight and length. Among infants of
      untreated women, 4.3% (n = 24) had neonatal hypoglycaemia compared with 2.5%
      (n=8302) among infants of women without bipolar disorder (1.51, 1.04 to 2.43),
      and 3.4% (n = 11) of the treated women (1.18, 0.64 to 2.16). The analyses of
      variation in outcomes did not support any significant differences between treated
      and untreated women. CONCLUSIONS: Bipolar disorder in women during pregnancy,
      whether treated or not, was associated with increased risks of adverse pregnancy
      outcomes.

PMID- 23137821
TI  - Cervical vestibular evoked myogenic potentials and vestibular migraine.

PMID- 23137822
TI  - The M235T single nucleotide polymorphism in the angiotensinogen gene is
      associated with coronary artery calcium in patients with a family history of
      coronary artery disease.
AB  - Little is known about the contribution of genetics and lipoprotein subclasses to
      the development of coronary artery calcification (CAC) in asymptomatic, first
      degree relatives of patients with CAD. We evaluated 100 asymptomatic, non
      smoking, lipid-lowering therapy-naive, first-degree relatives of patients with
      obstructive CAD through testing for 27 biomarkers, 15 single nucleotide
      polymorphisms in 12 candidate genes, and CAC and compared them to matched
      controls without family history. We compared prevalence of CAC in those with and
      without family history and biomarkers between those with and without CAC. Mean
      age was 41.6 +/- 9 years; 58% were female. Significantly more subjects with
      family history had non-zero CAC (median Agatston: 13, range 1-1107) compared to
      those without family history (median Agatston: 43; range 1-345) (21% vs. 9%; p =
      0.028). Among subjects with family history, in subjects with positive vs.
      negative CAC, multivariable analysis showed significantly lower HDL-2A (999 +/-
      333 vs. 1262 +/- 397 nmol/L) and higher frequency of a substitution of threonine
      for methionine at codon 235 in the angiotensinogen gene (AGT M235T) (75% vs. 54%;
      p < 0.05; odds ratio of 2.6 for CAC). Population attributable risk of one copy of
      the risk allele at the AGT locus was 16%, highest of any variable tested. In
      conclusion, in this population of healthy, low-risk subjects with a family
      history of CAD, the AGT M235T variant was the most significant predictor of CAC
      independent of blood pressure, raising the possibility of an alternative
      biological pathway.

PMID- 23137823
TI  - Acute elevation of lipids does not alter exercise hemodynamics in healthy men: A
      randomized controlled study.
AB  - OBJECTIVE: Exaggerated exercise blood pressure (BP) predicts mortality. Some
      studies suggest this could be explained by chronic hyperlipidemia, but whether
      acute-hyperlipidemia effects exercise BP has never been tested, and was the aim
      of this study. METHODS: Intravenous infusion of saline (control) and Intralipid
      were administered over 60 min in 15 healthy men by double-blind, randomized,
      cross-over design. Brachial and central BP (including, pulse pressure,
      augmentation pressure and augmentation index), cardiac output and systemic
      vascular resistance were recorded at rest and during exercise. RESULTS: Compared
      with control, Intralipid caused significant increases in serum triglycerides,
      very low density lipoproteins and free fatty acids (p < 0.001 for all). However,
      there was no significant difference for any exercise hemodynamic variable (p >
      0.05 for all). CONCLUSION: Acute-hyperlipidemia does not significantly change
      exercise hemodynamics in healthy males. Therefore, the association between raised
      lipids and increased exercise BP is likely due to the chronic effects of
      hyperlipidemia.

PMID- 23137824
TI  - Sleep-disordered breathing and retinal microvascular diameter.
AB  - BACKGROUND: Sleep-disordered breathing (SDB) is an emerging risk factor for
      cardiovascular disease (CVD). Microvascular dysfunction has been proposed as a
      potential mechanism in the pathogenesis of CVD in SDB. The retinal vasculature
      offers a unique opportunity to investigate the systemic effects of microvascular
      dysfunction as it can be viewed non-invasively and is also structurally and
      functionally similar to microvasculature elsewhere in the body. We therefore
      examined the association between SDB and retinal microvascular diameter after
      adjusting for major confounders. METHODS: We examined n = 476 participants from
      the Wisconsin Sleep Cohort Study. SDB was characterized using the apnea-hypopnea
      index (AHI) as <5 events/h, 5-14.9 events/h, and >=15 events/h. Outcomes of
      interest included the presence of retinal arteriolar narrowing (mean retinal
      arteriolar diameter <141.0 um) and retinal venular widening (mean venular
      diameter >223.0 um). RESULTS: Higher AHI was found to be positively associated
      with retinal venular dilatation, independent of body mass index, hypertension,
      diabetes, and lipid levels. Compared to an AHI of <5 events/h (referent), the
      multivariable-adjusted odds ratio of retinal venular widening for an AHI of 5
      14.9 events/h was 1.31 (0.75-2.28) and for an AHI of >15 events/h was 2.08 (1.03
      2.16); p-trend = 0.045. In contrast, there was no association between AHI and
      retinal arteriolar narrowing (p-trend = 0.72). CONCLUSION: Higher AHI, a marker
      of SDB, was positively associated with wider retinal venules, independent of age,
      gender, BMI, hypertension, diabetes, and lipid levels. These data suggest that
      the association of SDB with cardiovascular disease may be mediated, in part, by
      microvasculature.

PMID- 23137825
TI  - The association of obesity with abdominal aortic aneurysm presence and growth.
AB  - OBJECTIVES: The importance of obesity as a risk factor for atherothrombosis has
      been clearly demonstrated. Abdominal aortic aneurysm (AAA) is believed to develop
      due to mechanisms distinct from atherosclerosis. The aim of this systematic
      review was to critically assess published evidence examining: (1) the association
      of obesity with AAA presence; (2) the association of obesity with AAA growth.
      METHODS: Studies investigating the association of markers of obesity with AAA
      were identified by searching the PUBMED database and hand searching of article
      reference lists. To be eligible for inclusion studies had to report a recognised
      measure of adiposity, i.e. body mass index, waist circumference or an imaging
      technique to quantify adipose distribution. AAA presence and progression also had
      to be reported and assessed by ultrasound or computed tomography. Eight eligible
      studies assessed the association of obesity with AAA presence; and two studies
      which assessed the association of obesity with AAA growth were included. RESULTS:
      Of the eight studies that examined AAA presence, five studies examined body mass
      index (BMI) and three studies measured waist circumference (WC). Three of five
      studies reported that BMI was positively associated with AAA presence or
      increasing abdominal aortic diameter. Two of three studies reported that WC was
      positively associated with AAA presence or larger abdominal aortic diameter.
      Three of the included studies utilised secondary measures of adiposity: waist-to
      hip ratio (WHR), ultrasound assessment of adiposity and bioimpedence testing. Of
      these, only WHR was found to have a significant positive association with AAA
      presence. Of the two studies assessing the association of obesity with AAA growth
      both reported no association between BMI and AAA progression. CONCLUSION: The
      reviewed studies suggest that anthropometric measures of BMI and WC are
      associated with AAA presence. Currently there is no convincing data that obesity
      is associated with AAA growth but further studies employing more detailed
      anthropometric measures are needed.

PMID- 23137826
TI  - A preliminary study of the potential role of FGF-23 in coronary calcification in
      patients with suspected coronary artery disease.
AB  - OBJECTIVE: The association of fibroblast growth factor 23 (FGF-23) with vascular
      disease in patients with preserved renal function is not well understood. The
      purpose of this study was to investigate the relationship of serum FGF-23 with
      coronary calcification in patients without chronic kidney disease and diabetes
      mellitus (DM). METHODS: A cross-sectional study was performed in 148 consecutive
      patients with suspected coronary artery disease who underwent 64-slice computed
      tomography coronary angiography for diagnosis of coronary artery disease.
      Patients with eGFR <60 mL/min/1.73 m(2), proteinuria, or DM were excluded.
      Associations of coronary calcification (evaluated by Agatston score) were
      examined with classical risk factors and with inflammatory markers,
      adipocytokines and FGF-23. RESULTS: The median creatinine, eGFR and FGF-23 levels
      were 0.7 mg/dL, 74.6 mL/min/1.73 m(2), and 26 pg/mL respectively. The strongest
      association was found between age and Agatston score (r = 0.367, p < 0.001) in
      univariate logistic regression analysis. No atherogenic risk factors, including
      inflammatory markers and adipocytokine levels, were associated with Agatston
      score. Among calcium/phosphate metabolism markers, FGF-23 showed a weak but
      significant correlation with Agatston score (r = 0.169, p = 0.039). In
      multivariate linear regression analysis, age and FGF-23 (r = 0.188, p = 0.016)
      were independently associated with the Agatston score. CONCLUSION: Serum FGF-23
      levels were associated with coronary calcification independently of classical
      risk factors and of adipocytokines and inflammatory markers in patients with
      preserved renal function. FGF-23 may also have a direct effect on progression of
      coronary calcification and further studies are required to examine this issue.

PMID- 23137827
TI  - Increased expression of heparanase in symptomatic carotid atherosclerosis.
AB  - OBJECTIVE: Proliferation of smooth muscle cells (SMCs) can stabilize
      atherosclerotic lesions but the molecular mechanisms that regulate this process
      in humans are largely unknown. We have previously shown that heparan sulfate
      proteoglycans (HSPGs), such as perlecan, regulate SMC growth in animal models by
      modulating heparin-binding mitogens. Since perlecan is expressed at low levels in
      human atherosclerosis, we speculated that the effect of heparan sulfate (HS) in
      human disease was rather influenced by HS degradation and investigated the
      expression of heparanase (HPSE) in human carotid endarterectomies. METHODS AND
      RESULTS: Gene expression analysis from 127 endarterectomies in the BiKE database
      revealed increased expression of HPSE in carotid plaques compared with normal
      arteries, and a further elevation in symptomatic lesions. Increased HPSE protein
      expression in symptomatic plaque tissue was verified by tissue microarrays. HPSE
      mRNA levels correlated positively with expression of inflammatory markers IL-18,
      RANTES and IL-1beta, and also T-cell co-stimulatory molecules, such as B7.2,
      CD28, LFA-1 and 4-1BB. Previously reported single nucleotide polymorphisms within
      HPSE were associated with differential mRNA expression in plaques.
      Immunohistochemistry revealed that inflammatory cells were major producers of
      HPSE in plaque tissue. HPSE immunoreactivity was also observed in SMCs adjacent
      to the necrotic core and was co-localized to deposits of fibrin. CONCLUSIONS:
      This study demonstrates increased expression of HPSE in human atherosclerosis
      associated with inflammation, coagulation and plaque instability. Since HS can
      regulate SMC proliferation and influence plaque stability, the findings suggest
      that HPSE degradation of HS take part in the regulation of SMC function in human
      atherosclerosis.

PMID- 23137828
TI  - Acute exercise increases feeding latency in healthy normal weight young males but
      does not alter energy intake.
AB  - This study investigated the acute influence of exercise on eating behaviour in an
      ecologically valid setting whereby healthy active males were permitted complete
      ad libitum access to food. Ten healthy males completed two, 8h trials (exercise
      and control) in a randomised-crossover design. In the exercise trials
      participants consumed a breakfast snack and then rested for 1h before undertaking
      a 60 min run (72% of VO(2)max) on a treadmill. Participants then rested in the
      laboratory for 6h during which time they were permitted complete ad libitum
      access to a buffet meal. The timing of meals, energy/macronutrient intake and
      eating frequency were assessed. Identical procedures were completed in the
      control trial except no exercise was performed. Exercise increased the length of
      time (35 min) before participants voluntarily requested to eat afterwards.
      Despite this, energy intake at the first meal consumed, or at subsequent eating
      episodes, was not influenced by exercise (total trial energy intake: control 7426
      kJ, exercise 7418 kJ). Neither was there any difference in macronutrient intake
      or meal frequency between trials. These results confirm that food intake remains
      unaffected by exercise in the immediate hours after but suggest that exercise may
      invoke a delay before food is desired.

PMID- 23137829
TI  - Chloride anion effect on the advanced oxidation processes of methidathion and
      dimethoate: role of Cl2(.-) radical.
AB  - The reaction of phosphor-containing pesticides such as methidathion (MT) and
      dimethoate (DM) with dichloride radical anions (Cl(2)(.-)) was investigated. The
      second order rate constants (1.3 +/- 0.4) * 10(8) and (1.1 +/- 0.4) * 10(8) M(-1)
      s(-1) were determined for the reaction of Cl(2)(.-) with MT and DM, respectively.
      A reaction mechanism involving an initial charge transfer from the sulfide groups
      of the insecticides to Cl(2)(.-) is proposed and supported by the identified
      transient intermediates and reaction products. The formation of chlorinated
      byproducts was determined. The unexpected consequences of an efficient Cl(2)(.-)
      reactivity towards MT and DM on the degradation capacity by Advanced Oxidation
      Procedures applied to polluted waters containing the insecticides and Cl(-)
      anions is discussed.

PMID- 23137830
TI  - Electrochemical oxidation of electrodialysed reverse osmosis concentrate on Ti/Pt
      IrO2, Ti/SnO2-Sb and boron-doped diamond electrodes.
AB  - Reverse osmosis concentrate from wastewater reclamation contains biorefractory
      trace organic contaminants that may pose environmental or health hazard. Due to
      its high conductivity, electrochemical oxidation of brine requires low voltage
      which is energetically favourable. However, the presence of chloride ions may
      lead to the formation of chlorinated by-products, which are likely to exert an
      increased toxicity and persistence to further oxidation than their non
      chlorinated analogues. Here, the performance of Ti/Pt-IrO(2), Ti/SnO(2)-Sb and
      Si/BDD anodes was evaluated for the electrochemical oxidation of ROC in the
      presence of chloride, nitrate or sulfate ions (0.05 M sodium salts). In order to
      investigate the electrooxidation of ROC with nitrate and sulfate ions as dominant
      ion mediators, chloride ion concentration was decreased 10 times by
      electrodialytic pretreatment. The highest Coulombic efficiency for chemical
      oxygen demand (COD) removal was observed in the presence of high chloride ions
      concentration for all anodes tested (8.3-15.9%). Electrooxidation of the
      electrodialysed concentrate at Ti/SnO(2)-Sb and Ti/Pt-IrO(2) electrodes exhibited
      low dissolved organic carbon (DOC) (i.e. 23 and 12%, respectively) and COD
      removal (i.e. 37-43 and 6-22%, respectively), indicating that for these
      electrodes chlorine-mediated oxidation was the main oxidation mechanism,
      particularly in the latter case. In contrast, DOC removal for the electrodialysed
      concentrate stream was enhanced at Si/BDD anode in the presence of SO(4)(2-)
      (i.e. 51%) compared to NO(3)(2-) electrolyte (i.e. 41%), likely due to the
      contribution of SO(4)(.-) and S(2)O(8)(2-) species to the oxidative degradation.
      Furthermore, decreased concentration of chloride ions lead to a lower formation
      of haloacetic acids and trihalomethanes at all three electrodes tested.

PMID- 23137831
TI  - Effects of temperature and pH on the biokinetic properties of thiocyanate
      biodegradation under autotrophic conditions.
AB  - The simultaneous effects of temperature and pH on the biokinetic properties of
      thiocyanate biodegradation under mixed-culture, autotrophic conditions were
      investigated using response surface analysis (RSA) combined with biokinetic
      modeling. A partial cubic model, based on substrate inhibition biokinetics, was
      constructed for each kinetic coefficient in Andrew model (i.e., maximum specific
      growth rate (MU(m)), saturation coefficient (K(S)), and substrate inhibition
      coefficient (K(SI))). Each model proved statistically reliable to approximate the
      responses of the kinetic coefficients to temperature and pH changes (r(2) > 0.8,
      p < 0.05). The response surface plots demonstrated that the biokinetic
      coefficients change with respect to temperature and pH significantly and in
      different ways. The model response surfaces were substantially different to each
      other, indicating distinct correlations between the independent (temperature and
      pH) and dependent (model response) variables in the models. Based on the
      estimated response surface models, temperature was shown to have significant
      effects on all biokinetic coefficients tested. A dominant influence of
      temperature on MU(m) response was observed while the interdependence of
      temperature and pH was apparent in the K(S) and K(SI) models. Specific growth
      rate (MU) versus substrate (i.e., thiocyanate) concentration plots simulating
      using the obtained response surface models confirmed the significant effects of
      temperature and pH on the microbial growth rate and therefore on the thiocyanate
      degradation rate. Overall, the response surface models able to describe the
      biokinetic effects of temperature and pH on thiocyanate biodegradation within the
      explored region (20-30  degrees C and pH 6.0-9.0) were successfully constructed
      and validated, providing fundamental information for better process control in
      thiocyanate treatment.

PMID- 23137832
TI  - [Poisoning in children under age 7 in Spain. Areas of improvement in the
      prevention and treatment].
AB  - INTRODUCTION: To prevent acute poisoning in children we need to know in which
      circumstances they occur. OBJECTIVE: To analyse the circumstances of poisoning in
      children under 7 years-old and the management of these children in Spanish
      Paediatric Emergency Departments (SPED). MATERIAL AND METHODS: We perform a
      prospective study of charts of poisoned children less than 7 years admitted to 44
      hospitals between 2008 and 2011. RESULTS: A total of 400 poisoned children were
      recorded: 308 (77%) in children under 7 years, of whom 23 (7.5%) of them had
      previous episodes of poisoning in the family. More than half (230) occurred at
      home, mainly due to accidental ingestion (89.6%), of drugs (182, 59%), household
      products (75, 24.4%), and cosmetics (18, 5.8%). More than one-third (36.6%)
      contacted other departments before the patient reached SPED. A total of 160
      (51.9%) were treated in the hospital, and 45.4% were admitted in the hospital.
      None of them died. Drug poisoning required complementary tests more often (48.9%
      vs. 32% household products, and 11.1% cosmetics, P<.05), more treatments (64.8%
      vs. 36% and 16.6%, P<.0001) and more admissions (54.9% vs. 37.3% and 5.5%,
      P=.015), and 12.1% were not due to accidental ingestion but dosage errors (vs.
      2.6% and 0%, P<.05). Household product poisonings were more often related with
      storage in non-original packaging and being reachable by children. CONCLUSIONS:
      The most frequent poisonings seen in SPED were caused by the accidental ingestion
      of drugs and household products by children less than 7 years-old at home. Drug
      poisoning was potentially more risky. Drug and household product storage
      education, proper drug dosage and administration, and good advice are the main
      issues to prevent these poisonings.

PMID- 23137833
TI  - Influence of resveratrol on rheumatoid fibroblast-like synoviocytes analysed with
      gene chip transcription.
AB  - Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease that
      primarily attacks joints and is therefore a common cause of chronic disability
      and articular destruction. The hyperplastic growth of RA-fibroblast-like
      synoviocytes (FLSs) and their resistance against apoptosis are considered
      pathological hallmarks of RA. The natural antioxidant resveratrol is known for
      its antiproliferative and pro-apoptotic properties. This study investigated the
      effect of resveratrol on RA-FLS. RA-FLS were isolated from the synovium of 10 RA
      patients undergoing synovectomy or joint replacement surgery. RA-FLS were first
      stressed by pre-incubation with interleukin 1beta (IL-1beta) and then treated
      with 100 MUM resveratrol for 24h. In order to evaluate the influence of
      resveratrol on the transcription of genes, a Gene Chip Human Gene 1.0 ST Array
      was applied. In addition, the effect of dexamethasone on proliferation and
      apoptosis of RA-FLS was compared with that of resveratrol. Gene array analysis
      showed highly significant effects of resveratrol on the expression of genes
      involved in mitosis, cell cycle, chromosome segregation and apoptosis. qRT-PCR,
      caspase-3/7 and proliferation assays confirmed the results of gene array
      analysis. In comparison, dexamethasone showed little to no effect on reducing
      cell proliferation and apoptosis. Our in vitro findings point towards resveratrol
      as a promising new therapeutic approach for local intra-articular application
      against RA, and further clinical studies will be necessary.

PMID- 23137834
TI  - Biomolecular event trigger detection using neighborhood hash features.
AB  - The complex interactions between biomolecules and the consequences of these
      interactions are known as biomolecular events. Such events particularly in
      proteins play a key role in several aspects of proteomics. The major source of
      extraction of biomolecular events is the biomedical literature. Event trigger
      word detection is generally the first step in computationally mining the
      biomedical literature for biomolecular events. In this work, we study how to
      efficiently map the dependency graph of a candidate sentence into
      semantic/syntactic features, and use these semantic/syntactic features to detect
      bio-event triggers from the biomedical literature. The key factor in our method
      was the use of the hash operation to iteratively compute the dependency graph and
      utilize the properties of the hash operation to map the dependency graph into
      neighborhood hash features. The experimental results showed that neighborhood
      hash features can effectively represent the semantic/syntactic information in the
      sentence dependency graph. Furthermore, neighborhood hash features and basic
      features are complementary in the detection of biomolecular triggers. This
      approach, based on neighborhood hash features, achieved state-of-the-art
      performance on BioNLP datasets with respect to comparable evaluations.

PMID- 23137835
TI  - Predicting membrane protein types by incorporating protein topology, domains,
      signal peptides, and physicochemical properties into the general form of Chou's
      pseudo amino acid composition.
AB  - The type information of un-annotated membrane proteins provides an important hint
      for their biological functions. The experimental determination of membrane
      protein types, despite being more accurate and reliable, is not always feasible
      due to the costly laboratory procedures, thereby creating a need for the
      development of bioinformatics methods. This article describes a novel
      computational classifier for the prediction of membrane protein types using
      proteins' sequences. The classifier, comprising a collection of one-versus-one
      support vector machines, makes use of the following sequence attributes: (1) the
      cationic patch sizes, the orientation, and the topology of transmembrane
      segments; (2) the amino acid physicochemical properties; (3) the presence of
      signal peptides or anchors; and (4) the specific protein motifs. A new voting
      scheme was implemented to cope with the multi-class prediction. Both the training
      and the testing sequences were collected from SwissProt. Homologous proteins were
      removed such that there is no pair of sequences left in the datasets with a
      sequence identity higher than 40%. The performance of the classifier was
      evaluated by a Jackknife cross-validation and an independent testing experiments.
      Results show that the proposed classifier outperforms earlier predictors in
      prediction accuracy in seven of the eight membrane protein types. The overall
      accuracy was increased from 78.3% to 88.2%. Unlike earlier approaches which
      largely depend on position-specific substitution matrices and amino acid
      compositions, most of the sequence attributes implemented in the proposed
      classifier have supported literature evidences. The classifier has been deployed
      as a web server and can be accessed at http://bsaltools.ym.edu.tw/predmpt.

PMID- 23137836
TI  - Optimal control of an influenza model with seasonal forcing and age-dependent
      transmission rates.
AB  - This study considers an optimal intervention strategy for influenza outbreaks.
      Variations in the SEIAR model are considered to include seasonal forcing and age
      structure, and control strategies include vaccination, antiviral treatment, and
      social distancing such as school closures. We formulate an optimal control
      problem by minimizing the incidence of influenza outbreaks while considering
      intervention costs. We examine the effects of delays in vaccine production,
      seasonal forcing, and age-dependent transmission rates on the optimal control and
      suggest some optimal strategies through numerical simulations.

PMID- 23137837
TI  - Enhanced costimulation by CD70+ B cells aggravates experimental autoimmune
      encephalomyelitis in autoimmune mice.
AB  - OBJECTIVE: Assess whether CD70+ B cells contribute to EAE. MATERIALS AND METHODS:
      MOG-specific TCR transgenic mice (2D2) were crossed with mice with constitutive
      CD70 expression on B cells. The development of EAE and the phenotype of B-T
      lymphocytes were studied in 2D2xCD70 animals. RESULTS: Spontaneous EAE developed
      in 20% of 2D2xCD70 and 3% of 2D2 mice. EAE was also more severe in 2D2xCD70
      versus 2D2 animals upon MOG immunization. The susceptibility of 2D2xCD70 to EAE
      was associated with fewer FoxP3+ T cells. CONCLUSIONS: Expression of CD70 by B
      cells aggravates EAE possibly by reducing the number of regulatory T cells.

PMID- 23137838
TI  - Preparation and evaluation of mesalamine collagen in situ rectal gel: a novel
      therapeutic approach for treating ulcerative colitis.
AB  - Ulcerative colitis (UC) is a chronic inflammatory disease that primarily affects
      the colonic mucosa. Mesalamine had been established as a first line drug for
      treating mild to moderate UC. A continued availability of the drug for treatment
      of damaged tissues remains a great challenge today. In the present study, a novel
      mesalamine collagen in situ gel has been prepared using type I collagen, which is
      pH/temperature sensitive. This hydrogel undergoes sol-gel transition under
      physiological pH and temperature which was confirmed by rheological studies. The
      in vitro release profile demonstrated sustained release of mesalamine over a
      period of 12h. The in vivo efficacy of the in situ gel was performed using
      dextran sodium sulphate induced ulcerative colitis model in BALB/c mice. The
      clinical parameters such as, body weight changes, rectal bleeding and stool
      consistency were evaluated. In addition, the histopathological investigation was
      conducted to assess severity of mucosal damage and inflammation infiltrate. There
      was a significant reduction in rectal bleeding and mucosal damage score for
      collagen-mesalamine in situ gel group compared to the reference group. Apart from
      releasing mesalamine in controlled manner, the strategy of administering
      mesalamine through collagen in situ gel facilitates regeneration of damaged
      mucosa resulting in a synergistic effect for the treatment of ulcerative colitis.

PMID- 23137839
TI  - The Swedish Twin Registry: establishment of a biobank and other recent
      developments.
AB  - The Swedish Twin Registry (STR) today contains more than 194,000 twins and more
      than 75,000 pairs have zygosity determined by an intra-pair similarity algorithm,
      DNA, or by being of opposite sex. Of these, approximately 20,000, 25,000, and
      30,000 pairs are monozygotic, same-sex dizygotic, and opposite-sex dizygotic
      pairs, respectively. Since its establishment in the late 1950s, the STR has been
      an important epidemiological resource for the study of genetic and environmental
      influences on a multitude of traits, behaviors, and diseases. Following large
      investments in the collection of biological specimens in the past 10 years we
      have now established a Swedish twin biobank with DNA from 45,000 twins and blood
      serum from 15,000 twins, which effectively has also transformed the registry into
      a powerful resource for molecular studies. We here describe the main projects
      within which the new collections of both biological samples as well as phenotypic
      measures have been collected. Coverage by year of birth, zygosity determination,
      ethnic heterogeneity, and influences of in vitro fertilization are also
      described.

PMID- 23137840
TI  - Evaluation of protection in a mouse model after vaccination with Mycobacterium
      avium subsp. paratuberculois protein cocktails.
AB  - Whole-cell vaccines successfully reduce signs of clinical disease and fecal
      shedding of Mycobacterium avium subsp. paratuberculosis (MAP), however, these
      vaccines have some limitations. The present study was conducted to identify MAP
      proteins that might be candidates for the development of an improved vaccine. MAP
      proteins were screened for immunogenicity in naturally infected cattle and
      selected based upon reactivity in the interferon-gamma (IFN-gamma) and Western
      blot assays. Proteins (MAP1087, MAP1204, MAP1272c, and MAP2077c) were arrayed
      into 4 overlapping cocktails containing 3 proteins each. The efficacy of the
      proteins within these cocktails as vaccine candidates was evaluated by
      subcutaneous immunization of mice, followed by challenge with live, virulent MAP.
      All MAP protein cocktails significantly reduced the recovery of live MAP from the
      ileum, while cocktails 1 and 3 reduced colonization in the liver. No significant
      differences were seen in the mesenteric lymph node or spleen, however, cocktail 1
      reduced viable MAP in the mesenteric lymph node compared to other treatments.
      Stimulation of splenocytes upregulated antigen-specific IFN-gamma and IL-23
      secretion in all treatment groups, regardless of vaccination. Interestingly, IL-4
      was moderately downregulated for vaccinates compared to control infected mice. An
      increase in total CD25 expression was noted for 3 of the 4 vaccinate groups upon
      stimulation of splenocytes with a whole cell sonicate of MAP, with this effect
      becoming more significant within CD4CD25+ and CD8CD25+ subpopulations. The
      present study demonstrated that MAP proteins are useful as vaccine candidates to
      reduce MAP tissue burden.

PMID- 23137841
TI  - Immunisation of mice with Mycoplasma hyopneumoniae antigens P37, P42, P46 and P95
      delivered as recombinant subunit or DNA vaccines.
AB  - Porcine enzootic pneumonia (PEP), which is caused by the fastidious bacterium
      Mycoplasma hyopneumoniae, is one of the most economically important diseases in
      the pig industry worldwide. Commercial bacterins provide only partial protection;
      therefore, the development of more efficient vaccines against PEP is necessary.
      In this study, the cellular and humoral immune responses elicited by DNA and
      recombinant subunit vaccines based on the P37, P42, P46 and P95 antigens of M.
      hyopneumoniae were evaluated after the intramuscular inoculation of BALB/c mice.
      The expression of the cytokines INFgamma, TNFalpha and IL1 was evaluated by real
      time RT-PCR in splenocytes from vaccinated mice. All antigens delivered as
      subunit vaccines, especially P42 and P95, and the pcDNA3/P46 DNA vaccine were
      able to elicit strong immune responses. These vaccines induced cellular immune
      responses and the production of antibodies able to react with native M.
      hyopneumoniae proteins. Because both cellular and humoral immune responses were
      induced, P42 and P95 are promising candidates for a recombinant subunit vaccine
      and P46 is a promising candidate for a DNA vaccine against PEP.

PMID- 23137842
TI  - Impact of human papillomavirus (HPV) vaccination on HPV 16/18-related prevalence
      in precancerous cervical lesions.
AB  - BACKGROUND: Vaccination against human papillomavirus (HPV) types 16 and 18 is
      recommended for girls aged 11 or 12 years with catch-up vaccination through age
      26 in the U.S. Cervical intraepithelial neoplasia (CIN) grade 2 or 3 and
      adenocarcinoma in situ (CIN2+) are used to monitor HPV vaccine impact on cervical
      disease. This report describes vaccination status in women diagnosed with CIN2+
      and examines HPV vaccine impact on HPV 16/18-related CIN2+. METHODS: As part of a
      vaccine impact monitoring project (HPV-IMPACT), females 18-31 years with CIN2+
      were reported from pathology laboratories in CA, CT, NY, OR, TN from 2008 to
      2011. One diagnostic block was selected for HPV DNA typing with Roche Linear
      Array. Demographic, abnormal Papanicolaou (Pap) test dates and vaccine status
      information were collected. The abnormal Pap test immediately preceding the CIN2+
      diagnosis was defined as the 'trigger Pap'. RESULTS: Among 5083 CIN2+ cases
      reported to date, 3855 had vaccination history investigated; 1900 had vaccine
      history documented (vaccinated, with trigger Pap dates, or unvaccinated). Among
      women who initiated vaccination >24 months before their trigger Pap, there was a
      significantly lower proportion of CIN2+ lesions due to 16/18 compared to women
      who were not vaccinated (aPR=.67, 95% CI: .48-.94). Among the 1900 with known
      vaccination status, 20% initiated vaccination on/after their trigger screening.
      Women aged 21-23 years were more likely to initiate vaccination on/after the
      trigger Pap compared to 24-26 year olds (29.0% vs. 19.6%, p=.001), as were non
      Hispanic blacks compared to non-Hispanic whites (27.3% vs. 19.0%, p=.001) and
      publicly compared to privately insured women (38.1% vs. 17.4%, p<.0001).
      CONCLUSION: We found a significant reduction in HPV 16/18-related lesions in
      women with CIN2+ who initiated vaccination at least 24 months prior to their
      trigger Pap. These preliminary results suggest early impact of the HPV vaccine on
      vaccine-type disease, but further evaluation is warranted.

PMID- 23137844
TI  - The use of propolis as vaccine's adjuvant.
AB  - The success of many vaccines relies on their association with selected adjuvants
      in order to increase their immunogenicity and ensure long-term protection. All
      available adjuvants have adverse effects due to their toxicity and
      reactogenicity. Pre-clinical in vivo investigations can identify new natural
      products for further applications. Several studies have confirmed the different
      medicinal benefits of propolis. However the studies that addressed its use as a
      potent, safe, vaccine adjuvant were limited to specific countries and languages,
      primarily Chinese. Those studies introduced the use of different extracts and
      formulations of propolis as adjuvants for bacterial, viral, and parasitic
      vaccines. This comprehensive up-to-date review categorizes, documents, and
      discusses those trials in a clear chronological manner.

PMID- 23137845
TI  - Systemic immunization with an epitope-based vaccine elicits a Th1-biased response
      and provides protection against Helicobacter pylori in mice.
AB  - Vaccine-mediated Th1-biased CD4+ T cell responses have been shown to be crucial
      for protection against Helicobacter pylori (H. pylori). In this study, we
      investigated whether a vaccine composed of CD4+ T cell epitopes together with Th1
      adjuvants could confer protection against H. pylori in a mouse model. We
      constructed an epitope-based vaccine, designated Epivac, which was composed of
      predicted immunodominant CD4+ T cell epitopes from H. pylori adhesin A (HpaA),
      urease B (UreB) and cytotoxin-associated gene A product (CagA). Together with
      four different Th1 adjuvants, Epivac was administered subcutaneously and the
      prophylactic potential was examined. Compared to non-immunized mice, immunization
      with Epivac alone or with a Th1 adjuvant significantly reduced H. pylori
      colonization, and better protection was observed when an adjuvant was used.
      Immunized mice exhibited a strong local and systemic Th1-biased immune response,
      which may contribute to the inhibition of H. pylori colonization. Though a
      significant specific antibody response was induced by the vaccine, no correlation
      was found between the intensity of the humoral response and the protective
      effect. Our results suggest that a vaccine containing CD4+ T cell epitopes is a
      promising candidate for protection against H. pylori infection.

PMID- 23137843
TI  - T cell vaccinology: exploring the known unknowns.
AB  - The objective of modern vaccine development is the safe generation of protective
      long-term immune memory, both prophylactic and therapeutic. Live attenuated
      vaccines generate potent cellular and humoral immunity [1-3], but numerous
      problems exist with these vaccines, ranging from production and storage issues to
      adverse reactions and reversion to virulence. Subunit vaccines are safer, more
      stable, and more amenable to mass production. However the protection they produce
      is frequently inferior to live attenuated vaccines and is typically confined to
      humoral, and not cellular immunity. Unfortunately, there are presently no subunit
      vaccines available clinically that are effective at eliciting cellular responses
      let alone cellular memory [4]. This article will provide and overview of areas of
      investigation that we see as important for the development of vaccines with the
      capacity to induce robust and enduring cellular immune responses.

PMID- 23137846
TI  - Physiological, morphological, and immunochemical parameters used for the
      characterization of clinical and environmental isolates of Acanthamoeba.
AB  - The factors that characterize Acanthamoeba strains as harmless or potentially
      pathogenic have not been elucidated. Analysing the in vitro and in vivo
      parameters of Acanthamoeba samples, including heat tolerance at temperatures
      close to that of the human body, cytopathic effects, and their ability to cause
      infections in animals, has been proposed to identify their pathogenic potential.
      Another promising criterion for differentiating strains is the analysis of their
      biochemical and immunochemical properties. In this study, a comparative
      evaluation between clinical and environmental Acanthamoeba isolates was performed
      on the basis of physiological, morphological, and immunochemical criteria. Crude
      antigens were used to characterize the protein profiles by electrophoresis and
      immunize mice to produce polyclonal and monoclonal antibodies. The antibodies
      were characterized using ELISA, Western blotting, and immunofluorescence
      techniques. The results obtained with polyclonal antibodies suggest the presence
      of specific proteins for each studied isolate and co-reactive immunochemical
      profiles among conserved components. Ten monoclonal antibody clones were
      obtained; mAb3 recognized 3 out of 4 samples studied. The results of this study
      may help standardize criteria for identifying and characterizing Acanthamoeba
      strains. Taken together, our results support the view that a set of features may
      help differentiate Acanthamoeba species and isolates.

PMID- 23137847
TI  - Fetal sex pairing and adverse perinatal outcomes in twin gestations.
AB  - PURPOSE: To assess the association between fetal sex pairing in twin pregnancies
      and adverse perinatal and infant outcomes. METHODS: A retrospective cohort study
      of 9770 infants from 4885 twin pregnancies delivered in 2007 was conducted with a
      statewide hospital discharge database for Texas. Log-binomial regression models
      based on generalized estimating equations were used to calculate relative risks
      (RR) and 95% confidence intervals (95% CI) for the following dichotomous
      outcomes: breech presentation, hospital mortality, intrauterine growth
      restriction (IUGR), low birth weight, prolonged length of stay (>4 days), receipt
      of mechanical ventilation, and respiratory distress syndrome (RDS). RESULTS: The
      sample was composed of 4918 females and 4852 males. An approximately equal number
      of infants were from a female-female pregnancy (n = 3270), mixed-sex pregnancy (n
      = 3296), and a male-male pregnancy (n = 3204). Twins of either sex from mixed-sex
      pairs were 45% less likely to die in the hospital compared with females from a
      female-female pregnancy (RR, 0.55, 95% CI, 0.31-0.98). Males from a male-male
      pair were 33% less likely than females from female-female pairs to experience
      IUGR (RR, 0.67; 95% CI, 0.53-0.83). The incidence of RDS was significantly
      increased in males from male-male twin pairs versus females from female-female
      pairs (RR, 1.21; 95% CI, 1.05-1.41). CONCLUSIONS: Male infants from male-male
      twin pairs were more likely to develop RDS and be placed on a ventilator but less
      likely to experience IUGR than female infants from female-female pairs.

PMID- 23137848
TI  - Response to letter to the editor: 'the ground reaction vector in walking passes
      always (almost) through the same point'.

PMID- 23137849
TI  - False-positive ethyl glucuronide immunoassay screening caused by a propyl alcohol
      based hand sanitizer.
AB  - BACKGROUND: Urine ethyl glucuronide (EtG) is considered as a specific marker of
      recent ethanol consumption. We describe false-positive DRI((r)) EIA EtG enzyme
      immunoassay results caused by propyl glucuronides in urine after using a propanol
      based hand sanitizer. METHODS: EtG screening was done with the DRI((r)) EIA EtG
      assay (Microgenics), using a cut-off of 0.5 mg/L as recommended by the
      manufacturer and of 0.1 mg/L as demanded by the German Regulations for Reissuing
      Drivers Licenses. Confirmatory EtG analysis was done with the ClinMass((r)) EtG
      LC-MS/MS testkit (Recipe), extended by the mass transitions 235.1->75.1, 235.1
      >85.1, and 235.1->113.1 for the detection of the 1- and 2-propyl glucuronides.
      Self-experiments were done by staff members of our lab (n=7), using 3 mL
      Sterillium((r)) Classic Pure (30 g/100 g 1-propanol and 45 g/100 g 2-propanol)
      for hand sanitation every quarter of an hour for 8 h according to DIN EN
      1500:2011-05 with and without an exhauster and by passive inhalation of the
      sanitizer vapor. Spot urine samples were taken immediately before and up to 24 h
      after the first sanitizer use. RESULTS: False-positive immunoassay results of up
      to 4 mg/L or 2.3 mg/g creatinine were obtained after normal use of the sanitizer
      and also after passive inhalation of the sanitizer vapor (up to 0.89 mg/L or 0.61
      mg/g). Immunoassay results were positive even after 4-fold use of the sanitizer
      (up to 0.14 mg/L or 0.38 mg/g) and up to 6 h after the last sanitizer contact
      (maximum 0.63 mg/L and 0.33 mg/g for sanitizer users and 0.25 mg/g after passive
      inhalation). Spiking of EtG-free urine with 1-propyl glucuronide (Athena
      Environmental Sciences) between 0.05 and 10 mg/L clearly demonstrated a cross
      reaction of the immunoassay of approx. 10% as compared to EtG. LC-MS/MS of urines
      with a positive immunoassay EtG result did not show EtG signals, but distinct
      signals of 1-propyl glucuronide (n-propyl glucuronide) and 2-propyl glucuronide
      (iso-propyl glucuronide). An exhauster effectively prevented the inhalation of
      the sanitizer vapor, the formation of propyl glucuronides and thus false-positive
      DRI((r)) EIA EtG screening results, proving that propyl alcohols are almost
      exclusively taken up by respiration. CONCLUSIONS: The widespread use of propanol
      containing products such as hand sanitizers may lead to sufficient uptake of
      propyl alcohols and excretion of significant amounts of propyl glucuronides to
      yield false-positive DRI((r)) EIA EtG screening results. Thus, positive EtG
      immunoassay results have to be controlled by mass-spectrometry, in clinical cases
      at least if ethanol intake is denied by the patient.

PMID- 23137850
TI  - Novel adipokinetic hormones in the kissing bugs Rhodnius prolixus, Triatoma
      infestans, Dipetalogaster maxima and Panstrongylus megistus.
AB  - Peptides of the adipokinetic hormone (AKH)/red pigment-concentrating hormone
      (RPCH) family were isolated and sequenced from the retrocerebral corpora cardiaca
      of four kissing bugs which are all vectors of the protozoan Trypanosoma cruzi
      responsible for Chagas' disease. The sequence of three novel AKHs were deduced
      from the multiple MS(N) electrospray mass data: the octapeptide pGlu-Leu-Thr-Phe
      Ser-Thr-Asp-Trp amide (denoted Rhopr-AKH) in Rhodnius prolixus and Panstrongylus
      megistus, the nonapeptide pGlu-Leu-Thr-Phe-Thr-Pro-Asn-Trp-Gly amide (denoted
      Triin-AKH) in Triatoma infestans and the decapeptide pGlu-Leu-Thr-Phe-Ser-Asp-Gly
      Trp-Gly-Asn amide (denoted Dipma-AKH) in Dipetalogaster maxima. The sequences
      were confirmed by identical behavior of natural and synthetic forms in reversed
      phase HPLC and by CID-MS mass spectra. Conspecific injections of a dose of 10
      pmol of the respective synthetic peptides resulted in a small but significant
      increase of the lipid concentration in the hemolymph. These experiments suggest
      that AKHs in kissing bugs act to regulate lipid metabolism, possibly during
      dispersal flights which is one of the mechanisms whereby the insects reach new
      outbreak areas.

PMID- 23137851
TI  - Inhibition of Taq DNA polymerase by iridoid aglycone derivates.
AB  - Faithful replication of DNA molecules by DNA polymerases is essential for genome
      integrity and correct transmission of genetic information in all living
      organisms. DNA polymerases have recently emerged as important cellular targets
      for chemical intervention in the development of anti--cancer agents. Herein we
      report additional synthesis of simplified bicyclic aglycones of iridoids and
      their biological activity against Taq DNA polymerase with the object to find out
      some of the likely molecular targets implicated in the biological activity showed
      for this kind of compounds. The compounds 14, 33 and 34 showed inhibitory
      activity against Taq DNA polymerase with IC(50) values of 13.47, 17.65 and 18.31
      MUM, respectively. These results would allow proposing to DNA polymerases as the
      molecular targets implicated in this bioactivity and enhance the iridoid
      aglycones as leader molecule to develop new drugs for cancer therapy.

PMID- 23137852
TI  - Unraveling the effects of 1,25OH2D3 on global gene expression in pancreatic
      islets.
AB  - INTRODUCTION: Vitamin D deficiency has been linked to type 1 and 2 diabetes,
      whereas supplementation may prevent both diseases. However, the extent of the
      effects of vitamin D or its metabolites directly on pancreatic islets is still
      largely unknown. The aim of the present study was to investigate how active
      vitamin D, 1,25(OH)2D3, affects beta cells directly by establishing its effects
      on global gene expression in healthy murine islets. MATERIALS AND METHODS:
      Pancreatic islets were isolated from 2 to 3 week old C57BL/6 mice and cultured in
      vitro with 1,25(OH)2D3 or vehicle for 6 and 24h. Total RNA was extracted from the
      islets and the effects on global gene expression were analyzed using Affymetrix
      microarrays. RESULTS AND DISCUSSION: Exposure to 1,25(OH)2D3 compared to vehicle
      resulted in 306 and 151 differentially expressed genes after 6 and 24h,
      respectively (n=4, >1.3-fold, p<0.02). Of these 220 were up-regulated, whereas 86
      displayed a decreased expression after 6h. Furthermore, expression levels were
      increased for 124 and decreased for 27 genes following 24h of exposure. Formation
      of intercellular junctions, cytoskeletal organization, and intracellular
      trafficking as well as lipid metabolism and ion transport were among the most
      affected gene classes. Effects on several genes already identified as being part
      of vitamin D signaling in other cell types were observed along with genes known
      to affect insulin release, although with our assay we were not able to detect any
      effects of 1,25(OH)2D3 on glucose-stimulated insulin release from healthy
      pancreatic islets. CONCLUSION: The effects of 1,25(OH)2D3 on the expression of
      cytoskeletal and intracellular trafficking genes along with genes involved in ion
      transport may influence insulin exocytosis. However, an effect of 1,25(OH)2D3 on
      insulin release could not be detected for healthy islets in contrast to islets
      subjected to pathological conditions such as cytokine exposure and vitamin D
      deficiency as suggested by other studies. Thus, in addition to previously
      identified tolerogenic effects on the immune system, 1,25(OH)2D3 may affect basic
      functions of pancreatic beta cells, with the potential to render them more
      resistant to the detrimental conditions encountered during type 1 and 2 diabetes.
      This article is part of a Special Issue entitled 'Vitamin D Workshop'.

PMID- 23137854
TI  - The evaluation of hearing loss in children with celiac disease.
AB  - BACKGROUND AND AIMS: Celiac disease (CD) is an autoimmune enteropathy. The
      disease may be presented with extraintestinal manifestations including
      neurological findings. Epilepsy and ataxia are well known neurological disorders
      in CD. But there are very limited numbers of reports on sensory-neural hearing
      loss in CD in the literature. The aim of this study was to investigate the
      hearing functions in children with newly diagnosed CD. MATERIALS AND METHODS:
      Ninety-seven (194 ears) [56 girls, 41 boys (age range: 1.5-17 years)] newly
      diagnosed celiac disease patients and 85 sex and age-matched controls (170 ears)
      were included in this study. Hearing function was assessed by pure-tone
      audiometry, speech audiometry, tympanometry and otoacoustic emissions
      measurements. RESULTS: No significant difference were found between the patients
      and control groups measurements including the pure-tone audiometry, speech
      audiometry, tympanometry and otoacoustic emissions No significant difference was
      found for pure-tone audiometry, speech audiometry, tympanometry and otoacoustic
      emissions measurements in celiac patients according to the Marsh-Oberhuber
      classification (P>0.05). CONCLUSIONS: Our results showed that hearing functions
      of children with newly diagnosed CD were similar to healthy controls.

PMID- 23137853
TI  - Involvement of bone morphogenetic protein activity in somatostatin actions on
      ovarian steroidogenesis.
AB  - Somatostatin is expressed in the hypothalamus, pancreas and gastrointestinal
      tracts and it inhibits the secretion of various hormones in vivo. In the rodent
      ovary, somatostatin receptor (SSTR) subtypes 2 and 5 are expressed in granulosa
      cells and oocytes. Somatostatin analogs have been clinically used for treatment
      of endocrine tumors. For this purpose, relatively high-dose or long-term
      treatments of somatostatin analogs are necessary; however, the direct and
      continuous impact of somatostatin analogs on gonadal functions has yet to be
      elucidated. In the present study, we investigated the effects of somatostatin
      analogs (octreotide and pasireotide) on ovarian steroidogenesis by rat primary
      granulosa cell culture. The expression levels of SSTR2 and SSTR5 in granulosa
      cells were upregulated by FSH treatment. Treatment with somatostatin analogs
      decreased FSH-induced estradiol production with reduction in aromatase mRNA
      expression, while the treatment also suppressed FSH-induced progesterone
      production with reduction of mRNAs levels of StAR, P450scc and 3betaHSD2 in
      granulosa cells. This trend was also observed in a granulosa/oocyte co-culture
      condition. The effect of pasireotide was more potent than that of octreotide. FSH
      induced synthesis of steroids and cAMP was also suppressed by somatostatin analog
      treatment. Notably, pretreatment with a BMP-binding protein, noggin reversed the
      suppressive effects of somatostatin analogs on progesterone and cAMP production,
      suggesting that the endogenous BMP system is functionally involved in the SSTR
      effects in granulosa cells. Treatment with BMP-2, -4, -6 and -7 decreased the
      mRNA expression of inhibitory Smads6 and 7, leading to enhancement of BMP actions
      detected by Id-1 transcription in granulosa cells. Collectively, the results
      revealed that SSTR activation modulates ovarian steroidogenesis by upregulating
      endogenous BMP activity in growing follicles.

PMID- 23137855
TI  - Functional benefits of sequential bilateral cochlear implantation in children
      with long inter-stage interval between two implants.
AB  - OBJECTIVES: Older children are increasingly deriving binaural benefits from
      sequential bilateral cochlear implantation, and this procedure should be
      considered by experienced cochlear implant centers. This study aimed to identify
      the influence of a long inter-stage interval between two implants in older
      children. Speech perception and everyday listening performance were investigated
      and analyzed according to the length of the inter-stage interval. STUDY DESIGN
      AND SETTINGS: Forty-two children who received sequential bilateral cochlear
      implantation participated in this study. Their average ages at the first and
      second implantation were 4.2 and 9.7 years, respectively. All subjects acquired
      excellent speech performance from their first implant, and the mean inter-stage
      interval was 5.5 years. Speech perception in quiet was assessed by formal speech
      measures, and postoperative performance using the second implant only was
      compared with the preoperative performance. Speech perception in noise test was
      administered using three noise directions with noise (+10 dB signal-to-noise
      ratio) from front and 90 degrees  to each side, and the change in performance
      using the first implant only and both implants were analyzed across the three
      noise directions. Subjects were divided into three groups according to their
      inter-stage interval (group I, 3-4.9 years; group II, 5-6.9 years; and group III,
      7-9.9 years), and the test results were compared between the groups. Functional
      hearing benefits in daily life were measured by a questionnaire before and after
      bilateral cochlear implantation. RESULTS: The speech perception abilities in
      quiet using the second implant only improved quickly and were similar to those
      using the first implant only within 1 year after the second implantation. The
      scores for the monosyllabic word test (phoneme: p=0.052; word: p=0.125) and
      common phrases sentence test (p=0.062) 6 month after the second implantation, and
      the Categories of Auditory Performance score (p=1.000) 1 year after the second
      implantation using the second implant only did not differ significantly from
      those using the first implant only. Speech perception was significantly better
      using both implants than using the first implant in all three noise conditions
      (speech and noise in front: p=0.004; speech in front and noise to the first
      implant: p=0.003; speech in front and noise to the second implant: p<0.001), and
      the effect of noise direction was negligibly small. No salient influence of inter
      stage interval was observed in both quiet and noise tests. The second and third
      groups with longer inter-stage intervals (>5 years) achieved performance close to
      the level of the first group with a shorter interval. These subjects obtained
      significantly better functional hearing benefits in the everyday environment with
      bilateral implants compared with the first implant (p=0.018). CONCLUSION: The
      subjects in this study showed rapid postoperative progression within 6 months
      after the second implantation, and more listening benefits in noise and daily
      life with bilateral implants. This group of older children, who were good
      performers with the first implant, developed auditory perceptual competence in
      the second ear and achieved functional binaural benefits with their two implants.
      Sequential bilateral cochlear implantation should be recommended to this group of
      older children despite a long inter-stage interval between two implants.

PMID- 23137856
TI  - Recurrences in chronic tonsillitis substained by tonsillar biofilm-producing
      bacteria in children. Relationship with the grade of tonsillar hyperplasy.
AB  - OBJECTIVES: It has been suggested that bacterial biofilms are involved in chronic
      tonsillar disease, but there is a lack of strong evidence concerning their
      etiopathogenic role in childhood chronic tonsillar infections. The aim of this
      study was to assess the presence of biofilm-producing bacteria (BPB) in tonsillar
      bioptic specimens taken from children with recurrent exacerbations of chronic
      hyperplastic tonsillitis, and to evaluate the possible relationship between them
      and the patients' demographic and clinical characteristics. METHODS: 22 children
      (68.2% males; median age 6.5 years, range 3-13) with recurrent exacerbations of
      chronic hyperplastic tonsillitis were included. The presence of tonsillar BPB was
      assessed by means of the spectrophotometric analysis of tonsillar bioptic
      specimens taken during tonsillectomy between episodes of tonsillar infection.
      RESULTS: BPB were found in 50.0% of the 44 tonsillar specimens, and
      Staphylococcus aureus was the most frequent pathogen (81.8%). There was a
      significant relationship (p=0.02) between the grade of tonsillar hyperplasy (GTH)
      and the presence of tonsillar BPB, with an increased relative risk (RR=4.27,
      standard error=2.57, p<0.01) of tonsillar BPB development in children with GTH
      scores of >2. CONCLUSIONS: The findings of this study: (1) confirm the presence
      of tonsillar BPB in children with recurrent exacerbations of chronic tonsillar
      infections; (2) suggest that GTH is an important indicator of the presence of
      tonsillar BPB; and (3) raise the question as to whether tonsillar biofilm is a
      causative factor or just a consequence of recurrent exacerbations of chronic
      hyperplastic tonsillitis.

PMID- 23137857
TI  - Body dissatisfaction and disordered eating attitudes in 7- to 11-year-old girls:
      testing a sociocultural model.
AB  - We examined the sociocultural model of body dissatisfaction and disordered eating
      attitude development in young girls for the first time. According to the model,
      internalizing an unrealistically thin ideal body increases the risk of disordered
      eating via body dissatisfaction, dietary restraint, and depression. Girls aged 7
      11 years (N=127) completed measures of thin-ideal internalization, body
      dissatisfaction, dieting, depression, and disordered eating attitudes.
      Participants' height and weight were measured and their body mass index
      calculated. Thin-ideal internalization predicted disordered eating attitudes
      indirectly via body dissatisfaction, dietary restraint, and depression; it also
      predicted disordered eating attitudes directly. Path analyses showed that a
      revised sociocultural model fit well with the data. These data show that a
      sociocultural framework for understanding disordered eating and body
      dissatisfaction in adults is useful, with minor modifications, in understanding
      the development of related attitudes in young girls.

PMID- 23137858
TI  - Zinc and glycemic control: a meta-analysis of randomised placebo controlled
      supplementation trials in humans.
AB  - BACKGROUND: Impaired zinc metabolism is prominent in chronic disorders including
      cardiovascular disease and diabetes. Zinc has the potential to affect glucose
      homeostasis in animals and humans and hence impact the risk of type 2 diabetes
      mellitus. METHODS: A systematic review and meta-analysis of randomised placebo
      controlled trials was conducted to determine the effect of zinc supplementation
      on fasting blood glucose, HbA1c, serum insulin and serum zinc concentrations.
      Relevant studies for inclusion were identified from a literature search of
      electronic databases up to July 2011. RESULTS: Fourteen reports (n=3978 subjects)
      were included in the meta-analysis. In the overall analysis, a small but
      statistically significant reduction in fasting glucose concentrations was
      observed (-0.19+/-0.08mmol/L, P=0.013) after zinc supplementation. HbA1c tended
      to decrease in zinc-supplemented individuals (-0.64+/-0.36%, P=0.072). No
      significant effect was observed for serum insulin concentrations. Plasma zinc
      concentrations increased significantly following supplementation (+4.03+/
      0.81MUmol/L, P=0.001). In secondary analyses of participants with chronic
      metabolic disease (types 1 and 2 diabetes mellitus, metabolic syndrome and
      obesity), zinc supplementation produced a greater reduction in glucose
      concentrations (-0.49+/-0.11mmol/L, P=0.001) compared to the effect that was
      observed in healthy participants. CONCLUSION: The significant albeit modest
      reduction in glucose concentrations and tendency for a decrease in HbA1c
      following zinc supplementation suggest that zinc may contribute to the management
      of hyperglycemia in individuals with chronic metabolic disease.

PMID- 23137859
TI  - Can orthoses and navicular drop affect foot motion patterns during running?
AB  - OBJECTIVES: The purpose of this study was to examine the influence of semi-rigid
      foot orthoses on forefoot-rearfoot joint coupling patterns in individuals with
      different navicular drop measures during heel-toe running. DESIGN: Ten trials
      were collected from twenty-three male subjects who ran slowly shod at 170 steps
      per minute (2.23m/s) with a semi-rigid orthoses and without. METHODS: Forefoot
      rearfoot coupling motions were assessed using a vector coding technique during
      four intervals across the first 50% of stance. Subjects were divided into two
      groups based on navicular drop measures. A three way ANOVA was performed to
      examine the interaction and main effects of stance interval, orthoses condition
      and navicular drop (p<0.05). RESULTS: There were no interaction effects among
      stance interval, orthoses condition, or navicular drop (p=0.14) whereas an
      interaction effect of orthoses condition and stance interval was observed
      (p=0.01; effect size=0.74). Forefoot-rearfoot coupling motion in the no-orthoses
      condition increased from heel-strike to foot-flat phase at a rate faster than the
      orthoses condition (p=0.02). CONCLUSIONS: Foot orthoses significantly decrease
      the forefoot-rearfoot joint coupling angle by reducing forefoot frontal plane
      motion relative to the rearfoot. Navicular drop measures did not influence joint
      coupling relationships between the forefoot and rearfoot during the first 50% of
      stance regardless of orthotic condition.

PMID- 23137860
TI  - Antimalarial interaction of quinine and quinidine with clarithromycin.
AB  - Quinine (QN) and quinidine (QND) have been commonly used as effective and
      affordable antimalarials for over many years. Quinine primarily is used for
      severe malaria treatment. However, plasmodia resistance to these drugs and poor
      patient compliance limits their administration to the patients. The declining
      sensitivity of the parasite to the drugs can thus be dealt with by combining with
      a suitable partner drug. In the present study QN/QND was assessed in combination
      with clarithromycin (CLTR), an antibiotic of the macrolide family. In vitro
      interactions of these drugs with CLTR against Plasmodium falciparum (P.
      falciparum) have shown a synergistic response with mean sum fractional inhibitory
      concentrations (SigmaFICs) of <=1 (0.85 +/- 0.11 for QN + CLTR and 0.64 +/- 0.09
      for QND + CLTR) for all the tested combination ratios. Analysis of this
      combination of QN/QND with CLTR in mouse model against Plasmodium yoelii
      nigeriensis multi-drug resistant (P. yoelii nigeriensis MDR) showed that a dose
      of 200 mg/kg/day for 4 days of QN or QND produces 100% curative effect with 200
      mg/kg/day for 7 days and 150 mg/kg/day for 7 days CLTR respectively, while the
      same dose of individual drugs could produce only up to a maximum 20% cure. It is
      postulated that CLTR, a CYP3A4 inhibitor, might have caused reduced CYP3A4
      activity leading to increased plasma level of the QN/QND to produce enhanced
      antimalarial activity. Further, parasite apicoplast disruption by CLTR synergies
      the antimalarial action of QN and QND.

PMID- 23137861
TI  - Smoking in movies: a new centers for disease control and prevention core
      surveillance indicator.

PMID- 23137862
TI  - State quitlines and cessation patterns among adults with selected chronic
      diseases in 15 states, 2005-2008.
AB  - INTRODUCTION: The death rate of people who have a chronic disease is lower among
      former smokers than current smokers. State tobacco cessation quitlines are
      available for free in every state. The objective of our study was to compare
      demographic characteristics, use of quitline services, and quit rates among a
      sample of quitline callers. METHODS: We used data from 15 states on tobacco users
      aged 18 or older who enrolled with a quitline between October 1, 2005, and May
      31, 2008; 9 states also provided data from 7-month follow-up surveys. We used
      descriptive statistics and logistic regression to compare callers by disease
      status. RESULTS: Among 195,057 callers, 32.3% reported having 1 or more of the
      following chronic diseases: 17.7%, asthma; 5.9%, coronary artery disease; 11.1%,
      chronic obstructive pulmonary disease; and 9.3%, diabetes; 9.0% had 2 or more
      chronic diseases. Callers who had a chronic disease were older and better
      educated; more likely to be female, have Medicaid or other health insurance, and
      have used tobacco for 20 years or more; and less likely to quit smoking (22.3%)
      at 7 months than callers who had none of these chronic diseases (29.7%).
      CONCLUSION: About one-third of tobacco users who call state quitlines have a
      chronic disease, and those who have a chronic disease are less likely to quit
      using tobacco. Continued efforts are needed to ensure cessation treatments are
      reaching tobacco users who have a chronic disease and to develop and test ways to
      increase quit rates among them.

PMID- 23137863
TI  - Smoke-free-home rules among women with infants, 2004-2008.
AB  - INTRODUCTION: Exposure to secondhand smoke increases risk for infant illness and
      death. The objective of this study was to estimate the prevalence of complete
      smoke-free-home rules (smoking not allowed anywhere in the home) among women with
      infants in the United States. METHODS: We analyzed 2004-2008 data from the
      Pregnancy Risk Assessment Monitoring System on 41,535 women who had recent live
      births in 5 states (Arkansas, Maine, New Jersey, Oregon, and Washington). We
      calculated the prevalence of complete smoke-free-home rules and partial or no
      rules by maternal smoking status, demographic characteristics, delivery year, and
      state of residence. We used adjusted prevalence ratios (APRs) to estimate
      associations between complete rules and partial or no rules and variables.
      RESULTS: During 2004-2008, the overall prevalence of complete rules was 94.6%
      (95% confidence interval [CI], 94.4-94.9), ranging from 85.4% (Arkansas) to 98.1%
      (Oregon). The prevalence of complete rules increased significantly in 3 states
      from 2004 to 2008. It was lowest among women who smoked during pregnancy and
      postpartum, women younger than 20 years, non-Hispanic black women, women with
      fewer than 12 years of education, women who had an annual household income of
      less than $10,000, unmarried women, and women enrolled in Medicaid during
      pregnancy. CONCLUSION: The prevalence of complete smoke-free-home rules among
      women with infants was high overall and increased in 3 of 5 states, signifying a
      public health success. Sustained and targeted efforts among groups of women who
      are least likely to have complete smoke-free-home rules are needed to protect
      infants from exposure to secondhand smoke.

PMID- 23137864
TI  - Multiresidue analysis of 88 polar organic micropollutants in ground, surface and
      wastewater using online mixed-bed multilayer solid-phase extraction coupled to
      high performance liquid chromatography-tandem mass spectrometry.
AB  - An automated multiresidue method consisting of an online solid-phase extraction
      step coupled to a high performance liquid chromatography-tandem mass spectrometer
      (online-SPE-HPLC-MS/MS method) was developed for the determination of 88 polar
      organic micropollutants with a broad range of physicochemical properties
      (logD(OW) (pH 7): -4.2 to 4.2). Based on theoretical considerations, a single
      mixed-bed multilayer cartridge containing four different extraction materials was
      composed for the automated enrichment of water samples. This allowed the
      simultaneous analysis of pesticides, biocides, pharmaceuticals, corrosion
      inhibitors, many of their transformation products, and the artificial sweetener
      sucralose in three matrices groundwater, surface water, and wastewater. Limits of
      quantification (LOQs) were in the environmentally relevant concentration range of
      0.1-87 ng/L for groundwater and surface water, and 1.5-206 ng/L for wastewater.
      The majority of the compounds could be quantified below 10 ng/L in groundwater
      (82%) and surface water (80%) and below 100 ng/L in wastewater (80%). Relative
      recoveries were largely between 80 and 120%. Intraday and inter-day precision,
      expressed as relative standard deviation, were generally better than 10% and 20%,
      respectively. 50 isotope labeled internal standards were used for quantification
      and accordingly, relative recoveries as well as intraday and inter-day precision
      were better for compounds with corresponding internal standard. The applicability
      of this method was shown during a sampling campaign at a riverbank filtration
      site for drinking water production with travel times of up to 5 days. 36
      substances of all compound classes investigated could be found in concentrations
      between 0.1 and 600 ng/L. The results revealed the persistence of carbamazepine
      and sucralose in the groundwater aquifer as well as degradation of the metamizole
      metabolite 4-acetamidoantipyrine.

PMID- 23137865
TI  - Field enhanced bacterial sample stacking in isotachophoresis using wide-bore
      capillaries.
AB  - The isotachophoretic analysis of different bacterial strains was studied using
      capillaries with different internal diameters from 50 to 250 MUm. Several
      injection modes were investigated and compared in order to improve the limit of
      detection of bacteria by capillary isotachophoresis. A system suitability test
      obtained from the separation voltage was developed to ensure reliable results. As
      expected, the use of wider bore capillaries improved the analytical sensitivity
      of the isotachophoretic method when compared to the 50 MUm capillary. With the
      optimized conditions, the isotachophoretic method presented in this work allows
      the quantification of Erwinia carotovora (Gram negative bacteria) with a limit of
      detection as low as ~3000 cells mL(-1). The proposed methodology does not require
      any additive in the electrolyte such a fluorescent or chromophoric dye to reach
      these limits of detection.

PMID- 23137866
TI  - Quantification of achiral and chiral methylsulfonyl polychlorinated biphenyl
      metabolites by column-switching liquid chromatography-atmospheric pressure
      photoionization-tandem mass spectrometry.
AB  - An enantioselective heart-cut column-switching liquid chromatography-atmospheric
      pressure photoionization-tandem mass spectrometry method was developed for the
      analysis of 25 methylsulfonyl polychlorinated biphenyl metabolites in tissue
      extracts. Use of a pyrenyl-ethyl silica column in the first dimension enabled
      separation of all but two pairs of isobaric analytes. Enantioseparation was
      achieved for 9 out of the 10 atropisomeric analytes using a Chiralpak AD-H
      amylose-based column within 93 min, resulting in greater chromatographic
      resolution of enantioseparation over shorter analysis time by up to a factor of
      three, compared to previous one-dimensional and multi-dimensional gas
      chromatography-based methods. Precision for concentration and enantiomer fraction
      measurements was within 11% and 3% relative standard deviation, respectively.
      Limits of detection ranged from 0.01 to 1.73 ng on-column. Meta-congeners had
      poorer sensitivity (i.e., ng on-column), consistent with existing gas
      chromatography-based methods. Despite this limitation, the method was
      successfully applied to the analysis of Greenland sledge dog adipose tissue
      extracts, which had highly non-racemic residues of 4-methylsulfonyl-2,2',3,5',6
      pentachlorobiphenyl and 4'-methylsulfonyl-2,2',3,3',4,6'-hexachlorobiphenyl,
      consistent with past reports in Arctic mammals.

PMID- 23137867
TI  - Storage mite sensitisation is associated with early life village residence in
      Turkey.
AB  - BACKGROUND: Storage mites (SMs) occur in house-dust and the rate of sensitisation
      to them is high. We aimed to investigate if past and current living conditions
      are associated with the risk of SM sensitisation. METHODS: In total, 321 patients
      (70% females) aged 33.6 +/- 11.9 years (range: 14-68 years) were studied at our
      allergy unit between September 2009 and December 2010. Patients with persistent
      or intermittent rhinitis and/or asthma were included in the study. Skin prick
      tests (SPTs) for SMs (Lepidoglyphus destructor, Tyrophagus putrescentiae, and
      Acarus siro) and other common aeroallergens were performed. Demographic data and
      characteristics of the patients' homes were assessed via a questionnaire.
      RESULTS: In all, 102 (31.8%) patients were sensitised to >= 1 SM, of whom 43.1%
      were also sensitised to Dermatophagoides pteronyssinus. Comparison between the
      SPT-negative group (n = 129) and the SM-positive only group (n = 33) showed that
      having lived in a village during the first years of life was associated with SM
      sensitisation. Current place of residence was not significantly associated with
      any of the study variables. CONCLUSIONS: Living conditions have been changing and
      SM sensitisation may be associated with a history of village residence. The high
      rate of SM sensitisation observed in the study population might indicate the
      necessity of including those mite species in SPT panels, but the clinical
      relevance of sensitisation remains unclear. The clinical importance of SM
      sensitisation in urban areas should be investigated further.

PMID- 23137868
TI  - Expression of epidermal growth factors and a tight junction protein in the nasal
      mucosa of patients with chronic hypertrophic rhinitis.
AB  - BACKGROUND: ErbB family receptors and tight junction proteins participate in the
      pathologic process including tissue remodelling of inflammatory diseases in the
      upper and lower respiratory tracts. This study aimed at investigating the
      expressions of erbB1, 2, 3, 4, and a tight junction protein, claudin-1, in the
      nasal mucosa of patients with chronic hypertrophic rhinitis. METHODS: Inferior
      turbinates were collected from 10 turbinectomised patients with allergic and non
      allergic chronic hypertrophic rhinitis. The expressions of erbB1, 2, 3, 4, and
      claudin-1 were examined by fluorescence immunohistochemistry and by quantitative
      real-time transcription-polymerase chain reaction (qRT-PCR). RESULTS: All erbB1-4
      and claudin-1 were detected, and mainly localised in the epithelial cells and
      nasal gland cells. The immunoreactivity for claudin-1 was positively correlated
      with the expressions of erbB1, 2 and 4, but negatively correlated with that of
      erbB3. The mRNA expressions of erbB1, 2 and 4 were positively correlated with one
      another, whereas the expression of erbB3 showed negative correlation with the
      immunoreactivity for erbB2 and 4. CONCLUSIONS: These results suggest a possible
      participation of erbBs and claudin-1 in tissue remodelling in chronic
      hypertrophic rhinitis.

PMID- 23137870
TI  - Hypersensitivity to lansoprazole with tolerance to other proton pump inhibitors:
      does cross-reactivity between proton pump inhibitors really exist?

PMID- 23137869
TI  - The long-term outcomes of persistent childhood allergic asthma: a cross-sectional
      study from western Anatolia: childhood persistent asthma in western Anatolia.
AB  - BACKGROUND: Prospective cohort studies have provided useful knowledge about the
      natural history of asthma. However, most of the studies are conducted in western
      countries but the course of the disease and long-term outcomes may differ between
      countries due to environmental and cultural factors. OBJECTIVE: The aim of this
      study is to describe the long-term outcomes of childhood asthma, with data from a
      follow-up study of at least 10 years, in western Anatolia, Turkey. METHODS: Fifty
      two patients diagnosed with persistent allergic asthma participated in the study.
      The patient's demographics, findings on admission, age at onset of disease, time
      of diagnosis, history of other allergic conditions, history of parental asthma
      and allergic disorders, presence of pharmacotherapy and immunotherapy were
      obtained from patients' records. The factors influencing remission at the end of
      10 years follow-up were evaluated. RESULTS: A total of 20 patients (38.5%) were
      on remission at the end of 10 years. The type of allergen, multi-allergen
      sensitivity, eosinophilia and elevated serum immunoglobulin E on admission,
      accompanying allergic disorders and atopy in parents, and allergen immunotherapy
      did not affect the remission rate (p>0.05). CONCLUSION: Childhood persistent
      asthma is not a homogeneous clinical entity but high clinical remission rates are
      obtained in western Anatolia. There is no significant predictor of clinical
      remission in long term follow-up. Prospective studies should be performed in
      larger asthmatic populations to obtain further data about the natural course of
      childhood asthma.

PMID- 23137871
TI  - [Acceptability of vaccination against human papillomavirus (HPV) by
      pediatricians, mothers and young women in Ho Chi Minh City, Vietnam].
AB  - BACKGROUND: Cervical cancer (CC) is almost always induced by some oncogenic types
      of human papillomavirus (HPV). In Vietnam, it is the first leading cause of
      cancer in women, with highest prevalence in Ho Chi Minh City (HCMC). Since 2006,
      prevention of the CC has been improved by licensure of recombinant vaccines
      directed against HPV 16 and 18, effective when administered before the age of
      first sexual intercourse. A national program for routine immunization of pre
      adolescent girls in addition to cytological screening of adult women would
      greatly reduce the impact of CC in Vietnam but vaccines remain expensive and it
      is unclear how this strategy would be accepted by the target population. The aim
      of this study was to assess the acceptability of HPV vaccination by
      pediatricians, mothers with a daughter aged 9-15 years and young women aged 16-26
      years in HCMC. METHODS: Between March and June 2010, a cross-sectional survey of
      knowledge and attitudes was administered to 115 pediatricians in the pediatric
      hospital, 210 mothers and 400 young women attending the gynecology department of
      the University Hospital. RESULTS: Pediatricians generally had a good perception
      of the risk but they still lacked knowledge about HPV vaccination, given by 66%
      of them. Among mothers, 18% knew the relationship between HPV infection and CC,
      43% had heard of HPV vaccination and 40% agreed to vaccinate their daughter.
      Among young women, 35% knew the risk, 49% knew the vaccine and 38% wanted to be
      vaccinated. Level of education, amount of income and celibacy were positively
      related to intention to be vaccinated. The lack of information on HPV vaccination
      and the high cost of vaccines were the main causes of refusal or indecision.
      CONCLUSION: Routine HPV vaccination of girls in HCMC will be well accepted by the
      population if a large campaign of health education is implemented by the
      government and if the affordability of vaccines is facilitated.

PMID- 23137872
TI  - Emission and distribution of fumigants as affected by soil moistures in three
      different textured soils.
AB  - Water application is a low-cost strategy to control emissions of soil fumigant to
      meet the requirements of the stringent environmental regulations and it is
      applicable for a wide range of commodity groups. Although it is known that an
      increase in soil moisture reduces emissions, the range of soil moisture for
      minimizing emissions without risking pest control, is not well defined for
      various types of soils. With two column studies, we determined the effect of
      different soil moisture levels on emission and distribution of 1,3
      dichloropropene and chloropicrin in three different textured soils. Results on
      sandy loam and loam soils showed that by increasing soil moisture from 30% to
      100% of field capacity (FC), peak fluxes were lowered by 77-88% and their
      occurrences were delayed 5-15 h, and cumulative emissions were reduced 24-49%.
      For the sandy soil, neither peak fluxes nor the cumulative emissions were
      significantly different when soil moisture increased from 30% to 100% FC.
      Compared to the drier soils, the wetter soils retained consistently higher
      fumigant concentrations in the gas-phase, suggesting efficacy may not be impacted
      in these soils. The air-filled porosity positively and linearly correlated with
      the cumulative emission loss across all soil types indicating that it may serve
      as a good indicator for estimating emissions. These laboratory findings can be
      further tested under field conditions to conclude what irrigation regime should
      be used for increasing soil water content before fumigant application that can
      achieve maximum emission reduction and uniform fumigant distribution with high
      exposure index values.

PMID- 23137873
TI  - Risks from sediments contaminated with organochlorine pesticides in Hangzhou,
      China.
AB  - In September 2009, we investigated the residues, enantiomer fractions (EFs) and
      biological risks of organochlorine pesticides (OCPs), including
      dichlorodiphenyltrichloroethanes (DDTs) and hexachlorocyclohexanes (HCHs), in
      three different depth ranges (0-5 cm, 5-10 cm and 10-15 cm) of sediments from 15
      sites in Hangzhou, China. The concentration (ng g(-1) dryweight) ranges of HCHs
      and DDTs in surface sediments were 0.74-5.8 and 0.76-17, respectively. The
      vertical distribution of mean OCP concentrations was in the order of 10-15 cm>5
      10 cm>0-5 cm and implied that the residues of HCHs and DDTs gradually decreased
      after they were banned. The residues of OCPs in the study area mainly originated
      from the historical OCP use. The isomer ratios of <alpha>-HCH (alpha-HCH)/<gamma>
      HCH (gamma-HCH) (0.10-7.6) implied that HCH residues were derived not only from
      historical technical HCH use but also from additional use of lindane in this
      area. The isomer ratios of o,p'-DDT/p,p'-DDT (51% of samples were in the range of
      0.3-1.3) suggested that both dicofol-type DDT and technical DDT applications may
      be present in most study areas. The (+)-enantiomers of alpha-HCH and o,p'-DDT
      were more prevalent than (-)-enantiomer in most samples with the fractions
      contain different enantiomers greater than 0.5. DDTs, especially p,p'-DDE, are
      the main OCP species of more ecotoxicological concern in Hangzhou.

PMID- 23137874
TI  - Anthrax epizootic and migration: persistence or extinction.
AB  - In this paper, we use an extension of the deterministic mathematical model of an
      anthrax epizootic of Hahn and Furniss to study the effects of anthrax
      transmission, carcass ingestion, carcass induced environmental contamination, and
      migration rates on the persistence or extinction of animal populations. We
      compute the basic reproduction number R(0) for the anthrax epizootic model with
      and without taking into account animal migration. We obtained conditions for an
      anthrax enzootic region. We demonstrate that decreasing the levels of carcass
      ingestion by removal of carcases in game reserves, for example, may not always
      lead to a reduction in the population of animals infected with anthrax. However,
      increasing levels of carcass induced environmental contamination rates in an
      enzootic anthrax region can result in the catastrophic extinction of a persistent
      animal population.

PMID- 23137875
TI  - Association between two single nucleotide polymorphisms of PDCD6 gene and
      increased endometriosis risk.
AB  - Programmed cell death 6 (PDCD6), a calcium binding protein of the penta EF-hand
      protein family, and its receptors are involved in regulation of apoptosis
      pathways. To evaluate the relationship between genetic polymorphisms of PDCD6
      gene and endometriosis (ED) risk, we investigated the association of two single
      nucleotide polymorphisms (SNPs) of PDCD6 gene (rs4957014 and rs3756712) in 220
      endometriosis patients and 386 unrelated healthy controls. The genotypes of these
      two SNPs were determined by using polymerase chain reaction (PCR)-restriction
      fragment length polymorphism (RFLP) and DNA sequencing methods. Significantly
      increased endometriosis risk was observed to be associated with G allele of
      rs4957014 locus (OR=1.31, 95% CI=1.03-1.69). We have also observed increased ED
      risk was statistically associated with rs4957014 polymorphism in a dominant model
      (OR=1.52, 95% CI=1.09-2.13). Although no association has been found between ED
      risk and the allele frequencies of rs3756712 locus (a marginal P=0.066, OR=1.27,
      95% CI=0.98-1.65), but in a dominant model, increased endometriosis risk was
      significantly associated with rs3756712 polymorphism (OR=1.54, 95% CI=1.11-2.17).
      In conclusion, the current study indicates that PDCD6 gene may be a new
      susceptibility gene to endometriosis.

PMID- 23137876
TI  - Regulatory T cell kinetics in the peripheral blood of patients with Crohn's
      disease.
AB  - Estimates of T regulatory cell populations in the periphery of patients with
      Crohn's disease are confounded by disease activity and concomitant
      immunotherapeutic agents known to affect T cell proliferation and survival. We
      performed deuterium pulse/chase experiments in patients with quiescent Crohn's
      disease on no immunotherapy and healthy control subjects to estimate T regulatory
      cell kinetics. Quantification of deuterated DNA isolated from T cell subsets over
      10 days was determined by mass spectrophotometry. We demonstrate enhanced
      proliferation within the T regulatory cell population from patients with Crohn's
      disease when compared to non-T regulatory cells and T regulatory cells from
      healthy control subjects. We speculate that T regulatory cells isolated from the
      periphery of patients with Crohn's disease experience persistent antigen
      stimulation resulting in excess proliferative rates.

PMID- 23137877
TI  - HLA-E polymorphisms in an Afro-descendant Southern Brazilian population.
AB  - HLA-E is a non-classical I (Ib) gene which has limited polymorphism and low
      levels of tissue expression. Currently, 11 alleles are described in the
      literature with only three protein products. In the present study we investigated
      HLA-E gene variations at exons 2 and 3 and calculated allele, genotype and
      haplotype frequencies in a sample of 152 individuals who reported themselves as
      being Afro-descendants and who are voluntary bone marrow donors living in the
      state of Parana, Brazil. The most frequent allele in the sample analyzed was the
      E(*)01:01 (59.21%). The presence of the E(*)01:04 allele was not detected
      suggesting that it has a very low worldwide frequency or that this allele may be
      an artifact of sequencing. We reported the most frequent alleles found as well as
      genotypes and haplotypes and compared our results with the few other studies
      found in the literature. This study is the first to investigate Afro-descendants
      from the South of Brazil.

PMID- 23137878
TI  - Identification of a novel human leukocyte antigen allele B*46:34.
AB  - A new human leukocyte antigen (HLA) B allele was found in a healthy male Chinese
      Kazak individual. Sequencing-based typing (SBT) was used to identify and analyze
      the difference between the new allele and the closest matching HLA-B allele. HLA
      B(*)46 new allele has 1nt change from B(*)46:01:01 at nt 853 where G->C (condon
      260 GTA->CTA), resulting in a coding change: 260 Val is changed to Leu. The new
      HLA-B(*)46:34 allele was identified, and was named officially by the World Health
      Organization (WHO) Nomenclature Committee in June 2012. The GenBank sequence
      accession number is JX035785.

PMID- 23137879
TI  - Evaluation of IL17A expression and of IL17A, IL17F and IL23R gene polymorphisms
      in Brazilian individuals with periodontitis.
AB  - The IL23/Th17 axis plays an important role in the pathogenesis of cell-mediated
      tissue damage caused either by autoimmunity or immune responses against bacterial
      infection. Single nucleotide polymorphisms in the IL17A, IL17F and IL23R genes
      have been associated with several inflammatory diseases. However, these
      polymorphisms have not yet been studied in periodontitis. The aim of present
      study was to evaluate the expression of IL17A and occurrence of the IL17A
      (rs2275913), IL17F (rs763780) and IL23R (rs11209026) gene polymorphisms in
      different clinical forms or severity of periodontitis in a sample of Brazilian
      individuals. Peripheral blood was obtained from 30 non-smoker individuals and
      analyzed by flow cytometry to determine IL-17 expression. Genomic DNA was
      obtained from oral swabs in 180 individuals and analyzed by Real-time PCR. The
      study group was composed by individuals without periodontitis (control), with
      aggressive periodontitis (AP) and with chronic periodontitis (CP). Higher
      frequency of IL17A+CD4+ T cells was observed in control group. The A+ genotype
      from IL17A (rs2275913) was associated with lack of disease. No association was
      found considering the IL17F and IL23R polymorphisms. Our data suggest that IL17A
      and the presence of IL17A (rs2275913) A allele are associated with the absence of
      periodontal disease.

PMID- 23137880
TI  - Analysis of the adequate size of a cord blood bank and comparison of HLA
      haplotype distributions between four populations.
AB  - The number of units and especially the number of different HLA haplotypes present
      in a cord blood (CB) bank is a crucial determinant of its usefulness. We
      generated data relevant to the development of our national CB in Finland. The HLA
      haplotype distribution was examined between specific populations. We developed
      graphical ways of data presentation that enable easy visualization of
      differences. First, we estimated the optimal size of a CB bank for Finland and
      found that approximately 1700 units are needed to provide a 5/6 HLA-matched donor
      for 80% of Finnish patients. Secondly, we evaluated HLA haplotype distributions
      between four locations, Finland, Japan, Sweden and Belgium. Our results showed
      that the Japanese Tokyo Cord Blood Bank differs in both the frequency and
      distribution of haplotypes from the European banks. The European banks (Finnish
      Cord Blood Registry, The Swedish National Cord Blood Bank, and Marrow Donor
      Program-Belgium) have similar frequencies of common haplotypes, but 26% of the
      haplotypes in the Finnish CB bank are unique, which justifies the existence of a
      national bank. The tendency to a homogenous HLA haplotype distribution in banks
      underlines the need for targeting recruitment at the poorly represented minority
      populations.

PMID- 23137881
TI  - Transgenic sexing system for Ceratitis capitata (Diptera: Tephritidae) based on
      female-specific embryonic lethality.
AB  - Fruit fly pest species have been successfully controlled and managed via the
      Sterile Insect Technique (SIT), a control strategy that uses infertile matings of
      sterile males to wild females to reduce pest populations. Biological efficiency
      in the field is higher if only sterile males are released in SIT programs and
      production costs are also reduced. Sexing strains developed in the Mediterranean
      fruit fly Ceratitis capitata (medfly) through classical genetics are immensely
      beneficial to medfly SIT programs but exhibit reduced fertility and fitness.
      Moreover, transfer of such classical genetic systems to other tephritid species
      is difficult. Transgenic approaches can overcome this limitation of classical
      genetic sexing strains (GSSs), but had resulted so far in transgenic sexing
      strains (TSSs) with dominant lethality at late larval and pupal stages. Here we
      present a transgene-based female-specific lethality system for early embryonic
      sexing in medfly. The system utilizes the sex-specifically spliced transformer
      intron to restrict ectopic mRNA translation of the pro-apoptotic gene hid(Ala5)
      to females only. The expression of this lethal effector gene is driven by a
      tetracycline-repressible transactivator gene tTA that is under the control of
      promoters/enhancers of early-acting cellularization genes. Despite observed
      position effects on the sex-specific splicing, we could effectively establish
      this early-acting transgenic sexing system in the medfly C. capitata. After
      satisfactory performance in large scale tests, TSSs based on this system will
      offer cost-effective sexing once introduced into SIT programs. Moreover, this
      approach is straight forward to be developed also for other insect pest and
      vector species.

PMID- 23137882
TI  - Does BCG revaccination protect against the development of asthma?
AB  - Single BCG vaccination has been considered as a protective factor against asthma.
      However the effect of a second dose of BCG on the prevalence rate of asthma and
      asthma-allergic rhinitis-eczema comorbidity has not been studied exclusively
      among adolescents. In this ISAAC protocol-based cross sectional study we assessed
      the association between one single versus two doses of BCG among 2213 individuals
      aged 13-14 years old. We found no association between BCG revaccination and
      asthma, associated (OR = 0.68, 95% CI, 0.37-1.25) or not to allergic rhinitis
      and/or atopic eczema (OR = 1.07, 95% CI, 0.84-1.36).

PMID- 23137883
TI  - Pulmonary manifestations of anti-ARS antibody positive interstitial pneumonia-
      with or without PM/DM.
AB  - BACKGROUND: Autoantibodies against aminoacyl-tRNA synthetases (ARS) have been
      found to be highly specific for polymyositis and dermatomyositis (PM/DM) and to
      correlate strongly with complicating interstitial pneumonia (IP). The aim of the
      present study was to compare the clinical presentations of anti-ARS antibody
      positive IP patients with or without manifestations of PM/DM. METHODS: We
      retrospectively examined 36 IP patients with anti-ARS antibodies. Sixteen
      patients presented with and 20 without the features of PM/DM. They were divided
      into PM/DM-IP and idiopathic-IP (IIP) groups. Clinical symptoms, findings on
      physical examination, laboratory data, pulmonary function, computed tomography
      (CT), and bronchoalveolar lavage fluid (BALF) cell counts were compared. RESULTS:
      Skin findings, myalgia, and elevation of serum creatinine kinase were found in
      the PM/DM-IP group. Features common to both groups included: volume loss in lower
      bilateral lobes; ground-glass opacities, reticular shadows and traction
      bronchiectasis on chest CT; high percentage of lymphocytes (IIP: 44.0% +/- 21.0%
      (mean +/- SD), PM/DM-IP: 50.5% +/- 23.5%) and low CD4/8 ratios (IIP: 0.36 +/-
      0.34, PM/DM-IP: 0.44 +/- 0.42) in BALF; decreased pulmonary function, including
      percentage of predicted vital capacity (VC) (IIP: 80.1% +/- 15.4%, PM/DM-IP:
      73.6% +/- 16.4%), residual volume (RV) (IIP: 70.7% +/- 21.7%, PM/DM-IP: 71.5% +/-
      17.1%), total lung capacity (TLC) (IIP: 73.4% +/- 13.6%, PM/DM-IP: 71.6% +/-
      13.0%), and diffusing capacity DLco (IIP: 57.5% +/- 26.7%, PM/DM-IP: 46.4% +/-
      10.3%). Both groups achieved good responses to initial corticosteroid or
      immunosuppressant therapy. CONCLUSION: Patients with anti-ARS antibody-positive
      IP have common pulmonary manifestations regardless of the presence of PM/DM.

PMID- 23137885
TI  - The physician as an evolving moral actor.

PMID- 23137884
TI  - Chronic indeterminate phase of Chagas' disease: mitochondrial involvement in
      infection with two strains.
AB  - Chagasic cardiopathy has become one of the most frequent causes of heart failure
      and sudden death, as well as one of the most common causes of cardio-embolic
      stroke in Latin America. The myocyte response to oxidative stress involves the
      progression of cellular changes, primarily targeting the mitochondria and
      modifying therefore the energy supply. In this paper we analysed the effect of
      the infection of mice with 2 different strains of Trypanosoma cruzi (Tulahuen and
      SGO Z12) in the chronic indeterminate stage (75 days post-infection), upon the
      structure and function of cardiac mitochondria. The structural results showed
      that 83% of the mitochondria from the Tulahuen-infected mice presented an
      increase in their matrix and 91% of the mitochondria from the SGO Z12-infected
      group showed a reduction in their diameter (P < 0.05). When the Krebs cycle and
      mitochondrial respiratory chain functionality was analysed through the
      measurement of the citrate synthase and complexes I to IV activity, it showed
      that their activity was altered in all cases in a similar manner in both infected
      groups. In this paper we have demonstrated that the chronic indeterminate phase
      is not 'silent' and that cardiac mitochondria are clearly involved in the genesis
      and progression to the chronic chagasic cardiopathy when different factors alter
      the host-parasite equilibrium.

PMID- 23137886
TI  - "...Not as I do".

PMID- 23137887
TI  - Physicians and political advocacy.

PMID- 23137888
TI  - When Patients Worry about the Doctor.

PMID- 23137889
TI  - American medical association code of medical ethics' opinions on physicians'
      health and conduct.

PMID- 23137891
TI  - Home or hospital-your medical board is watching.

PMID- 23137890
TI  - Rousseau at the Roundtable-The Social Contract and the Physician's Responsibility
      to Society.

PMID- 23137892
TI  - Criminal convictions and medical licensure.

PMID- 23137893
TI  - Judging doctors-the person and the professional.

PMID- 23137894
TI  - Reconnecting to the moral core of the profession.

PMID- 23137895
TI  - The risks of professional protest.

PMID- 23137896
TI  - Doctors' Responsibility to Reduce Discrimination against Gay, Lesbian, Bisexual,
      and Transgender People.

PMID- 23137897
TI  - The Role of Retail Clinics in Today's Medical Care.

PMID- 23137898
TI  - About the contributors.

PMID- 23137899
TI  - Intelligence in childhood and chronic widespread pain in middle age: the National
      Child Development Survey.
AB  - Psychological factors are thought to play a part in the aetiology of chronic
      widespread pain. We investigated the relationship between intelligence in
      childhood and risk of chronic widespread pain in adulthood in 6902 men and women
      from the National Child Development Survey (1958 British Birth Cohort).
      Participants took a test of general cognitive ability at age 11 years; and
      chronic widespread pain, defined according to the American College of
      Rheumatology criteria, was assessed at age 45 years. Risk ratios (RRs) and 95%
      confidence intervals (CIs) were estimated using log-binomial regression,
      adjusting for sex and potential confounding or mediating factors. Risk of chronic
      widespread pain, defined according to the American College of Rheumatology
      criteria, rose in a stepwise fashion as intelligence fell (P for linear trend
      <0.0001). In sex-adjusted analyses, for an SD lower intelligence quotient, the RR
      of chronic widespread pain was 1.26 (95% CI 1.17-1.35). In multivariate backwards
      stepwise regression, lower childhood intelligence remained as an independent
      predictor of chronic widespread pain (RR 1.10; 95% CI 1.01-1.19), along with
      social class, educational attainment, body mass index, smoking status, and
      psychological distress. Part of the effect of lower childhood intelligence on
      risk of chronic widespread pain in midlife was significantly mediated through
      greater body mass index and more disadvantaged socioeconomic position. Men and
      women with higher intelligence in childhood are less likely as adults to report
      chronic widespread pain.

PMID- 23137900
TI  - Predictors for postpartum pelvic girdle pain in working women: the Mom@Work
      cohort study.
AB  - The objective of this study was to examine which factors during pregnancy and
      postpartum predict pelvic girdle pain (PGP) at 12 weeks postpartum among working
      women. A total of 548 Dutch pregnant employees were recruited in 15 companies,
      mainly health care, child care, and supermarkets. The definition of PGP was any
      pain felt in the pelvic girdle region at 12 weeks postpartum. Participants
      received questionnaires at 30 weeks of pregnancy and at 6 and 12 weeks postpartum
      with demographic, work-related, pregnancy-related, fatigue, psychosocial, PGP
      related and delivery-related questions. Univariate and multiple logistic
      regression analyses were performed. Almost half of the women experienced pain in
      their pelvic girdle at 12 weeks postpartum. However, the level of pain and the
      degree of disability due to postpartum PGP was low. Pregnancy-related predictors
      for PGP at 12 weeks were history of low back pain, higher somatisation, more than
      8 hours of sleep or rest per day, and uncomfortable postures at work. The
      pregnancy and postpartum-related predictors were: more disability at 6 weeks,
      having PGP at 6 weeks, higher mean pain at 6 weeks, higher somatisation during
      pregnancy and at 6 weeks postpartum, higher birth weight of the baby,
      uncomfortable postures at work and number of days of bed rest. Based on these
      results, it is concluded that extra attention should be given to women who
      experience PGP during pregnancy to prevent serious PGP during late pregnancy and
      postpartum. More research is needed to confirm the roles of hours of sleep,
      somatisation, and bed rest in relation to PGP.

PMID- 23137901
TI  - Synthesis of praseodymium hydroxide (Pr(OH)3) and praseodymium oxide (Pr6O11)
      nanorods via room temperature aging.
AB  - In this study, room-temperature aging has been investigated as an alternative to
      high-temperature hydrothermal processing for manufacturing Pr(OH)(3) nanorods. It
      was found that a simple process consisting of precipitation, washing, and room
      temperature aging results in the formation of Pr(OH)(3) nanorods that are
      structurally different to those synthesized by hydrothermal processing. Rather
      than single crystals, the nanorods were found to consist of crystals viewed down
      the [12-10] and [11-00] axes sharing a common [0001] growth direction. Subsequent
      calcination yielded Pr(6)O(11) nanorods consisting of cubic crystals viewed down
      the [11-0] and [11-2-] directions. The constituent crystals shared a common [110]
      direction parallel with the longitudinal rod axis.

PMID- 23137902
TI  - Effect of boundary slip and surface charge on the pressure-driven flow.
AB  - Drag reduction in micro/nanofluidic systems is an important issue. The effect of
      boundary slip and electrical double layer (EDL) induced by surface charge on the
      pressure-driven flow in a micro/nanochannel has been widely studied. However,
      change in electrical conductivity as a result of ionic redistribution caused by
      surface charge, which can affect the EDL-induced electrical force exerted on the
      flow, is often neglected. In addition, the effect of surface charge on the slip
      length is not considered. In this work, a model incorporating the effect of
      surface charge on electrical conductivity and slip length was developed to
      investigate the effect of boundary slip and EDL induced by surface charge on the
      volumetric flow rate and skin friction coefficient. The underlying mechanisms for
      the results regarding the effect of slip and surface charge on the flow were
      analyzed.

PMID- 23137903
TI  - Tuning drug release from smart microgel-hydrogel composites via cross-linking.
AB  - Soft nanocomposite hydrogels consisting of thermoresponsive microgels physically
      entrapped or covalently cross-linked to a non-thermoresponsive hydrogel are
      synthesized and tested for their capacity to facilitate long-term drug release of
      a small molecule drug. Copolymer microgels based on N-isopropylacrylamide and
      acrylic acid were synthesized that exhibited ionic affinity for binding to
      bupivacaine, a cationic local anesthetic. These microgels were subsequently
      physically entrapped within an in situ-gelling carbohydrate-based hydrogel
      network cross-linked via hydrazide-aldehyde chemistry; alternately, hydrazide
      functionalized microgels were prepared that covalently cross-linked to the bulk
      hydrogel phase. Both the overall rate of drug release and the magnitude of the
      burst release were significantly decreased when microgels were restricted from
      undergoing a phase transition between the preparation temperature of the
      nanocomposite (25 degrees C) and the test temperature (37 degrees C), whether
      deswelling was inhibited by increasing the cross-link density within the microgel
      itself or by cross-linking the microgel to the bulk hydrogel network. This result
      facilitates facile tuning of soft nanocomposite drug delivery systems to achieve
      targeted drug release kinetics.

PMID- 23137904
TI  - A new approach to the investigation of nanoparticles: electron tomography with
      compressed sensing.
AB  - The principal purpose of this contribution is to illustrate the potential of
      compressed sensing electron tomography for the characterisation of
      nanoparticulate materials that are vulnerable to electron beam damage. Not only
      is there growing interest in nanoparticles of organic materials in medical and
      allied contexts, there is also the need to investigate nanoparticles and
      nanoclusters of metals supported on biological macromolecular entities in the
      context of drug delivery. A qualitative account of the principles of electron
      tomography is outlined with illustrations from the field of heterogeneous
      catalysis, where electron beam damage is less of an issue, and an appendix deals
      with more quantitative aspects of how compressed sensing promises to expand the
      range of samples that have hitherto been accessible to investigation.

PMID- 23137905
TI  - Highly monodisperse polysilsesquioxane spheres: synthesis and application in
      cotton fabrics.
AB  - Highly monodisperse methyl-functionalized, vinyl-functionalized, and thiol
      functionalized polysilsesquioxane spheres (MPSQ, VPSQ, and MPPSQ spheres) have
      been successfully prepared through a one-pot emulsion approach with one
      organosilane as sole precursor in aqueous medium. The morphology, size
      distribution, and chemical structure were characterized by SEM, DLS, FT-IR, solid
      NMR, XRD, etc. The thermodecomposition and hydrophobicity of these spheres were
      investigated with TGA and water contact angle measurement. Our research turns out
      that the organofunctional groups play a key role in thermostability and
      hydrophobicity of polysilsesquioxane spheres, MPSQ, and VPSQ spheres possess
      better thermostability than MPPSQ spheres, the order of hydrophobicity is as
      follows: MPSQ>VPSQ>MPPSQ. Cotton fabrics can become superhydrophobic when treated
      with methyl- or vinyl-functional silica spheres.

PMID- 23137906
TI  - High-performance supercapacitor based on nitrogen-doped porous carbon derived
      from zinc(II)-bis(8-hydroxyquinoline) coordination polymer.
AB  - Nitrogen-doped porous carbon electrodes with remarkable specific capacitance have
      been fabricated by the rational carbonization of zinc(II)-bis(8-hydroxyquinoline)
      (abbr. Znq(2)) coordination polymer, and heating treatment with CO(NH(2))(2). The
      experimental results demonstrate that the mass ratio of carbon precursor and
      CO(NH(2))(2) plays a key role in the formation of porous carbon with various
      nitrogen content as well as specific surface areas and pore structures. The
      cyclic voltammetry and galvanostatic charge-discharge measurements show that the
      capacitive performance has been remarkably improved by doping with nitrogen. The
      specific capacitance of 219.2 F g(-1) is achieved at the current density of 1 A
      g(-1) with nitrogen-doped porous carbon, increasing up to ca. 56.8% compared to
      that with pristine porous carbon. The nitrogen-doped porous carbon electrode
      exhibits enhance capacitance retention as ca. 45.2% at 20 A g(-1) as well as
      cycling stability (ca. 7.6% loss after 3000 cycles). The present carbonization
      method as well as the nitrogen-doping method for porous carbon from coordination
      polymer can enrich the strategies for the production of carbon-based electrodes
      materials in the application of electrochemical capacitors.

PMID- 23137907
TI  - Quantitative analysis of exfoliation and aspect ratio of calcium niobate
      platelets.
AB  - This work employs tapping-mode AFM and dynamic light scattering (DLS) to
      investigate the effects of suspension composition (alkylammonium cation type,
      concentration) on the degree of exfoliation of a layered perovskite, calcium
      niobate (HCa(2)Nb(3)O(10), denoted as CNP). It is well known that in aqueous
      suspensions, tetrabutylammonium (TBA) cations intercalate CNP's layered
      structure, producing exfoliated platelets. This work shows that
      tetramethylammonium and tetraethylammonium cations do not produce significant
      levels of CNP exfoliation. However, TBA leads to complete exfoliation of CNP
      (>95%) in suspensions prepared with TBA:CNP ratios greater than 1:1. TGA and XRD
      data indicate that TBA uptake is limited by steric packing constraints. After
      depositing TBA-CNP platelets on mica surfaces for AFM imaging, quantitative image
      analysis provides the degree of exfoliation and distributions of platelet
      thickness, lateral size, and aspect ratio. The aspect ratio of TBA-CNP platelets
      has a lognormal distribution. Sedimentation of TBA-CNP suspensions under unit
      gravity removes unexfoliated particles from suspension, and centrifugation leads
      to differential sedimentation. The lateral size and aspect ratio of residual
      suspended TBA-CNP platelets decrease with increasing centrifugation speed. For
      all fractions of TBA-CNP platelets, the number-average lateral size from AFM
      agrees remarkably well with the effective spherical particle diameter measured by
      DLS.

PMID- 23137908
TI  - Numerical simulation of the drying of inkjet-printed droplets.
AB  - In this paper we study the behavior of an inkjet-printed droplet of a solute
      dissolved in a solvent on a solid horizontal surface by numerical simulation. An
      extended model for drying of a droplet and the final distribution of the solute
      on an impermeable substrate is proposed. The model extends the work by Deegan,
      Fischer and Kuerten by taking into account convection, diffusion and adsorption
      of the solute in order to describe more accurately the surface coverage on the
      substrate. A spherically shaped droplet is considered such that the model can be
      formulated as an axially symmetric problem. The droplet dynamics is driven by the
      combined action of surface tension and evaporation. The fluid flow in the droplet
      is modeled by the Navier-Stokes equation and the continuity equation, where the
      lubrication approximation is applied. The rate of evaporation is determined by
      the distribution of vapor pressure in the air surrounding the droplet. Numerical
      results are compared with experimental results for droplets of various sizes.

PMID- 23137909
TI  - Disposition and association of the steric stabilizer Pluronic(r) F127 in
      lyotropic liquid crystalline nanostructured particle dispersions.
AB  - Liquid crystalline nanostructured particles, such as cubosomes and hexosomes, are
      most often colloidally stabilised using the tri-block co-polymer Pluronic(r)
      F127. Although the effect of F127 on the internal particle nanostructure has been
      well studied, the associative aspects of F127 with cubosomes and hexosomes are
      poorly understood. In this study the quantitative association of F127 with
      phytantriol-based cubosomes and hexosomes was investigated. The amount of free
      F127 in the dispersions was determined using pressure ultra-filtration. The
      percentage of F127 associated with the particles plateaued with increasing F127
      concentration above the critical aggregation concentration. Hence the free
      concentration of F127 in the dispersion medium was proposed as a key factor
      governing association below the CMC, and partitioning of F127 between micelles
      and particles occurred above the CMC. The association of F127 with the particles
      was irreversible on dilution. The F127 associated with both the external and
      internal surfaces of the phytantriol cubosomes. The effects of lipid and F127
      concentration, lipid type, dilution of the dispersions and internal nanostructure
      were also elucidated. A greater amount of F127 was associated with cubosomes
      comprised of glyceryl monooleate (GMO) than those prepared using phytantriol.
      Hexosomes prepared using a mixture of phytantriol and vitamin E acetate (vitEA)
      had a greater amount of F127 associated with them than phytantriol cubosomes.
      Hexosomes prepared using selachyl alcohol had less F127 associated with them than
      phytantriol:vitEA-based hexosomes and GMO-based cubosomes. This indicated that
      both the lipid from which the particles are composed and the particle internal
      nanostructure have an influence on the association of F127 with lyotropic liquid
      crystalline nanostructured particles.

PMID- 23137910
TI  - Transporter gene expression in human head and neck squamous cell carcinoma and
      associated epigenetic regulatory mechanisms.
AB  - Expression levels of membrane transporters may affect the disposition, and
      thereby treatment efficacy, of anticancer drugs in human head and neck squamous
      cell carcinoma (HNSCC). Herein, we analyzed the gene expression profile of
      membrane transporters in HNSCC. In addition, we evaluated the mechanisms of
      transporter regulation in HNSCC and focused on the role of the nuclear pregnane X
      receptor (or NR1I2) and epigenetic mechanisms. Real-time RT-PCR revealed a
      significantly increased mRNA expression of membrane transporters SLCO1A2 and
      SLCO1B3 and a significantly decreased expression of transporters SLCO2B1,
      SLCO2A1, and ABCC3 in human HNSCC tumors compared with adjacent normal mucosa. An
      association between SLCO2B1 mRNA levels in tumors and 5-year survival of patients
      with HNSCC was observed (chi2 = 6.59, P = 0.010). Bisulfite sequencing revealed
      that promoter CpG islands of ABCC3 and SLCO2A1 were not hypermethylated,
      indicating that these genes were not epigenetically silenced in HNSCC tumors. In
      HNSCC-derived cell lines, transcript expression of transporters (e.g., ABCC3 or
      SLCO2A1; P < 0.001 for both) and NR1I2 (P < 0.001) was markedly induced by the
      DNA methyltransferase inhibitor, decitabine. Cotreatment with the prototypical
      pregnane X receptor activator, rifampicin, significantly reversed decitabine
      induced ABCC3 and SLCO2A1 expression. In summary, the expression of drug
      transporters (i) is markedly changed in HNSCC tumor tissues compared with normal
      mucosa, (ii) might be predictive of the outcome of patients with HNSCC, and (iii)
      is affected by novel epigenetic therapies and is further modulated by nuclear
      receptor-mediated mechanisms.

PMID- 23137912
TI  - Environmental fate of hexabromocyclododecane from a new Canadian electronic
      recycling facility.
AB  - An electronics recycling facility began operation at the municipal landfill site
      for the City of Edmonton, Canada in March 2008 with the goal of processing 30,000
      tonnes of electronic wastes per year. Of the many by-products from the process,
      brominated fire retardants such as hexabromocyclododecane (HBCD) can evolve off
      of e-wastes and be released into the environmental media. HBCD has been
      identified by many countries and international bodies as a chemical of concern
      because of its ability to bioaccumulate in the ecosystem. An evaluation of the
      potential emission of HBCD indicates that up to 500 kg per year may be released
      from a landfill and recycling facility such as that operating in Edmonton. A
      multimedia fugacity model was used to evaluate the dispersion and fate of
      atmospherically emitted HBCD traveling into surrounding agricultural land and
      forested parkland. The model indicates that the three isomers of HBCD partitioned
      into environmental media similarly. Much of the HBCD is lost through atmospheric
      advection, but it is also found in soil and sediment. Modeled air concentrations
      are similar to those measured at locations with a history of e-waste recycling.
      Since HBCD has been shown to bioaccumulate, the HBCD released from this source
      has the long-term potential to affect agricultural food crops and the park
      ecosystem.

PMID- 23137911
TI  - In patients with chronic stable angina, secondary prevention appears better in
      the very old compared to younger patients: the Coronary Artery Disease in gENeral
      practiCE (CADENCE) Substudy.
AB  - BACKGROUND: With our aging communities and the increased prevalence of coronary
      heart disease (CAD) with age, the impact of this disease in the very old warrants
      further investigation. OBJECTIVE: To assess health outcomes and the attainment of
      guideline-based secondary prevention targets in the very old (>80 years, n=482)
      as compared to young (<65 years, n=582) and elderly (between 65 and 80 years,
      n=932) patients, all of whom had chronic stable angina. DESIGN: The coronary
      artery disease in general practice (CADENCE) study was a cluster-stratified cross
      sectional survey. This study reports on health outcomes quantitated using the
      Seattle Angina Questionnaire and guideline targets achieved for blood pressure,
      smoking, lipids, diabetic control and body habitus. SETTINGS AND PARTICIPANTS:
      2031 stable angina patients were recruited from 207 primary care practices.
      RESULTS: Despite similar angina frequency scores, the very old were more
      physically impaired by their angina than both the young and elderly [76+/-25
      (Young) vs. 70+/-26 (Elderly) vs. 63+/-28 (Very old), p<0.05 for both
      comparisons]. However, the very old had better quality of life scores than young
      stable angina patients [72+/-24 vs. 65+/-25, p<0.05] and were similar to the
      elderly [72+/-24 vs. 72+/-23, p>0.05]. Also blood pressure, lipid, diabetic and
      body habitus targets were more often achieved in the very old and elderly
      patients compared to young stable angina patients. CONCLUSION: Despite similar
      symptomatic status and greater physical limitations, the very old reported a
      better quality of life and more often achieved treatment targets than young
      stable angina patients. Failure to improve secondary prevention measures in
      younger age groups may potentially contribute to increased morbidity in older
      age, and failure to achieve 'Healthy Ageing'.

PMID- 23137913
TI  - Options for managing hypoxic blackwater events in river systems: a review.
AB  - Blackwater events are characterised by a high concentration of dissolved organic
      carbon in the water column. They occur naturally in lowland rivers with forested
      floodplains and bring a variety of benefits to both aquatic and floodplain biota.
      However, particularly when accompanied by high temperatures, respiration of the
      organic carbon may cause blackwater to become hypoxic. This may lead to a range
      of lethal and sub-lethal effects on the aquatic biota. We review the current
      scientific knowledge concerning the management of blackwater and hypoxia, and
      examine how this knowledge may be applied to the management of hypoxic blackwater
      events in lowland river systems. A range of management options, which aim to
      either prevent the development of hypoxic blackwater or to reintroduce oxygen
      into deoxygenated waters, are reported. Mitigation options that may be applicable
      to lowland river systems include manipulating the season and magnitude of floods
      in regulated rivers, increasing roughness in flow paths, establishing oxygenated
      refugia for aquatic biota and introducing hydraulic structures that promote
      turbulence and re-aeration. With climatic changes trending towards a scenario
      where extreme events leading to the development of hypoxic blackwater are more
      probable, it is now vital to validate and optimise management options on local
      and regional scales and work towards closing knowledge gaps. With judicious
      management of regulated rivers, it is possible to minimise the impacts of hypoxic
      flows while preserving the benefits brought to floodplain and river ecosystems by
      seasonal flooding and carbon exchange.

PMID- 23137914
TI  - Electrochemical removal of microcystin-LR from aqueous solution in the presence
      of natural organic pollutants.
AB  - Removal of microcystin-LR (MC-LR) from water was evaluated using an electro
      oxidation process. Different operating parameters were investigated, including
      current density, reaction time, anode material and type of supporting
      electrolyte. The current density and the type of anode material played an
      important role in the MC-LR degradation efficiency, whereas the type of sodium
      salts influenced the removal efficiency. The degradation of MC-LR was mainly
      attributed to direct anodic oxidation. The best operating conditions (98% of MC
      LR removal) for MC-LR (initial concentration of 11-13 MUg L(-1)) degradation in
      solution were obtained at a current density of 38 mA cm(-2) for 60 min with a
      recycling rate of 0.1 L min(-1) using a Ti/BDD anode in the presence of 0.2 g L(
      1) of Na(2)SO(4). The colour caused by the presence of natural organic matter
      (humic acid) could be diminished by up to 81%. Likewise, MC-LR decomposition
      exhibited first-order reaction behaviours with a rate coefficient of 0.049 min(
      1).

PMID- 23137915
TI  - A removal mechanism for organics and nitrogen in treating leachate using a semi
      aerobic aged refuse biofilter.
AB  - A removing mechanism for organics and nitrogen using a semi-aerobic aged refuse
      biofilter (SAARB) was evaluated based on the space structure, the aged refuse
      conformation and characteristics, as well as the degradation theories of organic
      matter and nitrogen-based substances, which could provide a fundamental theory to
      more effectively treat organic matter and nitrogen-based pollutants in leachate.
      The experimental results indicated that the average removal rate of chemical
      oxygen demand and total nitrogen reached 96.61 and 95.46%, respectively. The
      aerobic-anoxic-anaerobic zones appeared alternately in both the space structure
      and the granule conformation inside of the SAARB, which promoted various
      physical, chemical and biological reactions. Most biodegradable organic matter
      was converted to CO(2) and CH(4). The average CO(2) release rate was 1.567 L/(h
      m(2)) in the winter and 1.467 L/(h m(2)) in the summer during a single-period
      experiment. The average CH(4) release rate was 0.303 L/(h m(2)) in the summer;
      however, it could not be detected in the winter. Moreover, the nitrogen-based
      pollutants were mostly converted to N(2) and N(2)O through denitrification. Some
      of the refractory organic matter and nitrogen-based pollutants were likely
      adsorbed by the aged refuse and biodegraded more slowly. The adsorption rate of
      biologically degradable matter (BDM) was 0.624 g/(kg d) during the first 40 weeks
      and the largest absorbance of total nitrogen (TN) was about 7.0 g/kg during this
      experiment. Therefore, the SAARB can maintain stable and highly efficient
      environment for removing organic matter and nitrogen-based pollutants.

PMID- 23137916
TI  - Short-term usage of sewage sludge as organic fertilizer to sugarcane in a
      tropical soil bears little threat of heavy metal contamination.
AB  - A field experiment was carried out to study the effect of application rates of
      sewage sludge and mineral nitrogen and phosphate fertilizers on As, Ba, Cd, Cr,
      Cu, Ni, Pb, Se, and Zn concentration in soil, cane plant, and first ratoon
      (residual effect) in a Typic Hapludult soil. To allow an analysis by means of
      response surface modeling, four rates of sewage sludge (0, 3.6, 7.2 and 10.8 t
      ha(-1), dry base), of N (0, 30, 60 and 90 kg ha(-1)) and of P(2)O(5) (0, 60, 120
      and 180 kg ha(-1)) were applied in randomized block design, in a 4 * 4 * 4
      factorial scheme, with confounded degrees of freedom for triple interaction, with
      two replications. To evaluate the residual effect of the sludge applied to cane
      plant on the cane ratoon growth, mineral NK fertilizers were applied at the rates
      of 120 kg ha(-1) N and 140 kg ha(-1) of K(2)O, on all treatments. The application
      rates of mineral nitrogen and phosphate fertilizers did not affect statistically
      the heavy metal concentration in the soil and in the sugarcane plants. Sewage
      sludge application increased As, Cd, Cu, Ni, Pb, and Zn concentrations in soil,
      but values did not exceed the quality standard established by legislation for
      agricultural soils. Although the concentrations of metals in the plants were very
      low, the uptake of heavy metal by sugarcane plants was generally increased by
      sewage sludge doses. The use of sewage sludge based on N criteria introduces a
      small amount of heavy metal into the agricultural system, however it poses no
      hazard to the environment.

PMID- 23137917
TI  - Interactive spatial tools for the design of regional adaptation strategies.
AB  - Regional adaptation strategies are plans that consist of feasible measures to
      shift a region towards a system that is flexible and robust for future climate
      changes. They apply to regional impacts of climate change and are imbedded in
      broader planning. Multiple adaptation frameworks and guidelines exist that
      describe the development stages of regional adaptation strategies. Spatial
      information plays a key role in the design of adaptation measures as both the
      effects of climate change as well as many adaptation measures have spatial
      impacts. Interactive spatial support tools such as drawing, simulation and
      evaluation tools can assist the development process. This paper presents how to
      connect tasks derived from the actual development stages to spatial support tools
      in an interactive multi-stakeholder context. This link helps to decide what
      spatial tools are suited to support which stages in the development process of
      regional adaptation strategies. The practical implication of the link is
      illustrated for three case study workshops in the Netherlands. The regional
      planning workshops combine expertise from both scientists and stakeholders with
      an interactive mapping device. This approach triggered participants to share
      their expertise and stimulated integration of knowledge. 

PMID- 23137918
TI  - Study of the scapular muscle latency and deactivation time in people with and
      without shoulder impingement.
AB  - Changes in muscle activities are commonly associated with shoulder impingement
      and theoretically caused by changes in motor program strategies. The purpose of
      this study was to assess for differences in latencies and deactivation times of
      scapular muscles between subjects with and without shoulder impingement. Twenty
      five healthy subjects and 24 subjects with impingement symptoms were recruited.
      Glenohumeral kinematic data and myoelectric activities using surface electrodes
      from upper trapezius (UT), lower trapezius (LT), serratus anterior (SA) and
      anterior fibers of deltoid were collected as subjects raised and lowered their
      arm in response to a visual cue. Data were collected during unloaded, loaded and
      after repetitive arm raising motion conditions. The variables were analyzed using
      2 or 3 way mixed model ANOVAs. Subjects with impingement demonstrated
      significantly earlier contraction of UT while raising in the unloaded condition
      and an earlier deactivation of SA across all conditions during lowering of the
      arm. All subjects exhibited an earlier activation and delayed deactivation of LT
      and SA in conditions with a weight held in hand. The subjects with impingement
      showed some significant differences to indicate possible differences in motor
      control strategies. Rehabilitation measures should consider appropriate training
      measures to improve movement patterns and muscle control.

PMID- 23137919
TI  - Enhanced temporal resolution at cardiac CT with a novel CT image reconstruction
      algorithm: initial patient experience.
AB  - OBJECTIVE: To evaluate the effect of a temporal resolution improvement method
      (TRIM) for cardiac CT on diagnostic image quality for coronary artery assessment.
      MATERIALS AND METHODS: The TRIM-algorithm employs an iterative approach to
      reconstruct images from less than 180 degrees  of projections and uses a
      histogram constraint to prevent the occurrence of limited-angle artifacts. This
      algorithm was applied in 11 obese patients (7 men, 67.2 +/- 9.8 years) who had
      undergone second generation dual-source cardiac CT with 120 kV, 175-426 mAs, and
      500 ms gantry rotation. All data were reconstructed with a temporal resolution of
      250 ms using traditional filtered-back projection (FBP) and of 200 ms using the
      TRIM-algorithm. Contrast attenuation and contrast-to-noise-ratio (CNR) were
      measured in the ascending aorta. The presence and severity of coronary motion
      artifacts was rated on a 4-point Likert scale. RESULTS: All scans were considered
      of diagnostic quality. Mean BMI was 36 +/- 3.6 kg/m(2). Average heart rate was 60
      +/- 9 bpm. Mean effective dose was 13.5 +/- 4.6 mSv. When comparing FBP- and TRIM
      reconstructed series, the attenuation within the ascending aorta (392 +/- 70.7
      vs. 396.8 +/- 70.1 HU, p>0.05) and CNR (13.2 +/- 3.2 vs. 11.7 +/- 3.1, p>0.05)
      were not significantly different. A total of 110 coronary segments were
      evaluated. All studies were deemed diagnostic; however, there was a significant
      (p<0.05) difference in the severity score distribution of coronary motion
      artifacts between FBP (median=2.5) and TRIM (median=2.0) reconstructions.
      CONCLUSION: The algorithm evaluated here delivers diagnostic imaging quality of
      the coronary arteries despite 500 ms gantry rotation. Possible applications
      include improvement of cardiac imaging on slower gantry rotation systems or
      mitigation of the trade-off between temporal resolution and CNR in obese
      patients.

PMID- 23137920
TI  - iPSCs for personalized medicine: what will it take for Africa?
AB  - Induced pluripotent stem cells (iPSCs) are cutting edge biotechnology that may
      revolutionize medicine, and creating iPSCs from ethnically diverse individuals
      would generate valuable therapeutic and drug development tools. However,
      challenges must be overcome in creating the infrastructure and scientific
      capacity needed to pursue innovative, leapfrogging strategies to make iPSCs
      available in Africa.

PMID- 23137921
TI  - Systematic review: 3-factor versus 4-factor prothrombin complex concentrate for
      warfarin reversal: does it matter?
AB  - INTRODUCTION: Prothrombin complex concentrates are used for rapid reversal of
      vitamin K antagonists in patients with bleeding or those requiring surgery or
      invasive procedures. Current guidelines suggest 4-factor products are preferred
      over 3-factor prothrombin complex concentrates. MATERIALS AND METHODS: We
      performed a systematic review comparing the effectiveness of 3-factor to 4-factor
      prothrombin complex concentrates in normalizing the international normalized
      ratio to <= 1.5 in patients with acquired coagulopathy due to vitamin K
      antagonist use. Studies reporting administration of prothrombin complex
      concentrates for emergent reversal of vitamin K antagonists that included results
      of baseline prothrombin time/international normalized ratio and follow-up testing
      within 60 minutes of prothrombin complex concentrates administration were
      included. RESULTS: A total of 18 studies were included representing 654 patients.
      The most common indications for prothrombin complex concentrate were
      intracerebral hemorrhage, urgent surgery or invasive procedure, and
      gastrointestinal bleeding. Baseline international normalized ratio values ranged
      from 3.3-5.1 in the 3-factor group and from 2.3 to greater than 20 in the 4
      factor group. The international normalized ratio repeated within one hour of
      prothrombin complex concentrates administration ranged from 1.2-1.9 in the 3
      factor group and 1.0-1.9 in the 4-factor group. International normalized ratio
      decreased to <= 1.5 within one hour after prothrombin complex concentrates
      administration in 6 of 9 studies in the 3-factor group, and 12 of 13 studies in
      the 4-factor group. CONCLUSION: More reliable correction of the international
      normalized ratio was seen with 4-factor compared to 3-factor prothrombin complex
      concentrates which may have clinical implications since 4-factor products are
      unavailable in some countries.

PMID- 23137923
TI  - Non parametric, self organizing, scalable modeling of spatiotemporal inputs: the
      sign language paradigm.
AB  - Modeling and recognizing spatiotemporal, as opposed to static input, is a
      challenging task since it incorporates input dynamics as part of the problem. The
      vast majority of existing methods tackle the problem as an extension of the
      static counterpart, using dynamics, such as input derivatives, at feature level
      and adopting artificial intelligence and machine learning techniques originally
      designed for solving problems that do not specifically address the temporal
      aspect. The proposed approach deals with temporal and spatial aspects of the
      spatiotemporal domain in a discriminative as well as coupling manner. Self
      Organizing Maps (SOM) model the spatial aspect of the problem and Markov models
      its temporal counterpart. Incorporation of adjacency, both in training and
      classification, enhances the overall architecture with robustness and
      adaptability. The proposed scheme is validated both theoretically, through an
      error propagation study, and experimentally, on the recognition of individual
      signs, performed by different, native Greek Sign Language users. Results
      illustrate the architecture's superiority when compared to Hidden Markov Model
      techniques and variations both in terms of classification performance and
      computational cost.

PMID- 23137922
TI  - From cells to chromatin: capturing snapshots of genome organization with 5C
      technology.
AB  - In eukaryotes, genome organization can be observed on many levels and at
      different scales. This organization is important not only to reduce chromosome
      length but also for the proper execution of various biological processes. High
      resolution mapping of spatial chromatin structure was made possible by the
      development of the chromosome conformation capture (3C) technique. 3C uses
      chemical cross-linking followed by proximity-based ligation of fragmented DNA to
      capture frequently interacting chromatin segments in cell populations. Several 3C
      related methods capable of higher chromosome conformation mapping throughput were
      reported afterwards. These techniques include the 3C-carbon copy (5C) approach,
      which offers the advantage of being highly quantitative and reproducible. We
      provide here an updated reference protocol for the production of 5C libraries
      analyzed by next-generation sequencing or onto microarrays. A procedure used to
      verify that 3C library templates bear the high quality required to produce
      superior 5C libraries is also described. We believe that this detailed protocol
      will help guide researchers in probing spatial genome organization and its role
      in various biological processes.

PMID- 23137924
TI  - In elderly women moderate hypercholesterolemia is associated to endothelial and
      microcirculatory impairments.
AB  - How cholesterol influences the microcirculation on aging subjects is not well
      known. This study evaluated moderate hypercholesterolemia effects in, treated or
      not, lean elderly women on brachial artery reactivity and microcirculatory
      function using venous occlusion plethysmography (VOP) and nailfold
      videocapillaroscopy (NVC). Patients (mean age 73 years) were divided into healthy
      elderly (HE, n=15), treated dyslipidemia with statins during at least 6 months
      (TDL, n=9) and dyslipidemia (DL, n=9, cholesterol, 257+/-11 and LDL-cholesterol,
      157+/-24 mg/dl). Young, mean age 23 years, women (YC, n=24), served as controls.
      Laboratory and anthropometrical analysis, VOP peak forearm blood flow (FBF)
      during the reactive hyperemia response/baseline FBF (%HYPER) and peak FBF after
      0.4 mg sublingual nitroglycerin/baseline FBF (%NITRO) were assessed. NVC
      capillary density and diameters, maximum red blood cell velocity (RBCV(max))
      during reactive hyperemia/baseline RBCV and time to reach RBCV(max) were
      evaluated. Correlations between %HYPER, %NITRO and plasma cholesterol fractions
      were performed. Total and LDL-cholesterol were increased only in DL group.
      Capillary diameters were larger in elderly groups than YC. RBCV(max)/baseline
      RBCV was reduced in the DL group compared to HE, TDL and YC. %HYPER was lower in
      DL and normalized in TDL group. YC %HYPER was double of HE. %NITRO decreased from
      (HE=YC) to TDL and DL groups. There was a significant inverse correlation between
      LDL-cholesterol, non-HDL-cholesterol and %HYPER/% Nitro. In conclusion, moderate
      hypercholesterolemia reversibly impaired the vasodilatatory response in the
      microcirculation but the endothelial-independent vasodilator response to
      nitroglycerine remained irreversibly lower in healthy aged women.

PMID- 23137926
TI  - Guidelines and good clinical practice recommendations for Contrast Enhanced
      Ultrasound (CEUS) in the liver - update 2012: A WFUMB-EFSUMB initiative in
      cooperation with representatives of AFSUMB, AIUM, ASUM, FLAUS and ICUS.
AB  - Initially, a set of guidelines for the use of ultrasound contrast agents was
      published in 2004 dealing only with liver applications. A second edition of the
      guidelines in 2008 reflected changes in the available contrast agents and updated
      the guidelines for the liver, as well as implementing some non-liver
      applications. Time has moved on, and the need for international guidelines on the
      use of CEUS in the liver has become apparent. The present document describes the
      third iteration of recommendations for the hepatic use of contrast enhanced
      ultrasound (CEUS) using contrast specific imaging techniques. This joint WFUMB
      EFSUMB initiative has implicated experts from major leading ultrasound societies
      worldwide. These liver CEUS guidelines are simultaneously published in the
      official journals of both organizing federations (i.e., Ultrasound in Medicine
      and Biology for WFUMB and Ultraschall in der Medizin/European Journal of
      Ultrasound for EFSUMB). These guidelines and recommendations provide general
      advice on the use of all currently clinically available ultrasound contrast
      agents (UCA). They are intended to create standard protocols for the use and
      administration of UCA in liver applications on an international basis and improve
      the management of patients worldwide.

PMID- 23137927
TI  - Use of antibacterial agents in the neonate: 50 years of experience with
      vancomycin administration.
AB  - Neonatal sepsis, classified as either early or late onset, has specific pathogen
      distribution and infection rates in the different neonatal age groups. It is a
      major cause of mortality and morbidity and administration of antibiotics is
      urgently required for suspected or proven infection. Vancomycin is the first
      choice treatment of late onset sepsis due to resistant staphylococci. Although it
      has been used for more than 50 years, prescription remains a challenge in
      neonatal intensive care units for many reasons, including: high pharmacokinetic
      variability, numerous presentations, lack of consensus on dosing regimen and
      therapeutic drug monitoring. In addition, recent concerns about the increase in
      minimal inhibition concentration and other more generic problems have prompted
      reappraisal of the rational use of vancomycin. This article highlights the goal
      of optimising vancomycin therapy in the neonate and discusses future research
      directions. Specific attention is given to dosing optimisation of vancomycin to
      avoid resistance and maximise the likelihood of achieving the therapeutic target.
      Modelling and simulation approaches have clear advantages in dosing optimisation
      of antimicrobial agents in the neonate. Neonatologists and paediatric
      pharmacologists should work closely together to achieve this goal.

PMID- 23137928
TI  - Dielectrophoretic concentration of low-abundance nanoparticles using a
      nanostructured tip.
AB  - Electric field-induced concentration has the potential for application in highly
      sensitive detection of nanoparticles (NPs) for disease diagnosis and drug
      discovery. Conventional two-dimensional planar electrodes, however, have shown
      limited sensitivity in NP concentration. In this paper, the dielectrophoretic
      (DEP) concentration of low-abundance NPs is studied using a nanostructured tip
      where a high electric field of 3 * 10(7) V m(-1) is generated. In experimental
      studies, individual 2, 10, and 100 nm Au NPs are concentrated to a nanotip using
      DEP concentration and are detected by scanning transmission and scanning electron
      microscopes. The DEP force on Au NPs near the end of a nanotip is computed
      according to the distance, and then compared with Brownian motion-induced force.
      The computational study shows qualitative agreement with the experimental
      results. When the experimental conditions for DEP concentration are optimized for
      8 nm-long oligonucleotides, the sensitivity of a nanotip is 10 aM (10 attomolar;
      nine copies in a 1.5 MUl sample volume). This DEP concentrator using a nanotip
      can be used for molecular detection without amplification.

PMID- 23137925
TI  - Cutaneous microvascular dysfunction correlates with serum LDL and sLOX-1 receptor
      concentrations.
AB  - The human cutaneous circulation is an accessible and representative regional
      circulation for investigating mechanisms of microvascular dysfunction, a systemic
      disease process occurring early in the pathogenesis of atherosclerosis. Elevated
      concentrations of low-density lipoproteins ([LDL]) are highly atherogenic and
      independently associated with the severity of coronary atherosclerosis through
      their actions on the lectin-like oxidized LDL receptors (LOX-1). We hypothesized
      that cutaneous microvascular dysfunction, as measured by a decrement in
      endothelial nitric oxide- (NO-) dependent vasodilation during local heating,
      would be correlated with serum [LDL], oxidized [LDL], and soluble LOX-1 receptors
      [sLOX-1]. Intradermal microdialysis fibers were placed in the skin of 53
      otherwise healthy men and women (aged 52+/-8 years) whose serum [LDL] ranged from
      72 to 233 mg/dL. Skin blood flow was measured by laser Doppler flowmetry over a
      local forearm skin site as it was heated (42 degrees C) to induce sustained local
      vasodilation. After flux plateaued, L-NAME was infused to block endothelial NO
      synthase in order to determine the NO-dependent portion of the vasodilatory
      response. Data were normalized to maximal cutaneous vascular conductance (CVC).
      NO-dependent vasodilation was reduced as a linear function of [LDL] (R(2)=0.303,
      p<0.001), oxidized [LDL] (R(2)=0.214, p<0.001), and [sLOX-1] (R(2)=0.259,
      p=0.026) but was unrelated to high-density lipoprotein (HDL) concentration
      (R(2)=0.003, p=0.68). Hypercholesterolemia-induced microvascular dysfunction is
      related to various LDL markers and involves a reduction in NO-dependent
      vasodilation that appears to be a progressive process measurable in the skin
      microcirculation.

PMID- 23137930
TI  - Safety assessment of boron by application of new uncertainty factors and their
      subdivision.
AB  - The available toxicity information for boron was reevaluated and four appropriate
      toxicity studies were selected in order to derive a tolerable daily intake (TDI)
      using newly proposed uncertainty factors (UFs) presented in Hasegawa et al.
      (2010). No observed adverse effect levels (NOAELs) of 17.5 and 8.8 mgB/kg/day for
      the critical effect of testicular toxicity were found in 2-year rat and dog
      feeding studies. Also, the 95% lower confidence limit of the benchmark doses for
      5% reduction of fetal body weight (BMDL(05)) was calculated as 44.9 and 10.3
      mgB/kg/day in mouse and rat developmental toxicity studies, respectively.
      Measured values available for differences in boron clearance between rats and
      humans and variability in the glomerular filtration rate (GFR) in pregnant women
      were used to derive chemical specific UFs. For the remaining uncertainty, newly
      proposed default UFs, which were derived from the latest applicable information
      with a probabilistic approach, and their subdivided factors for toxicokinetic and
      toxicodynamic variability were applied. Finally, overall UFs were calculated as
      68 for rat testicular toxicity, 40 for dog testicular toxicity, 247 for mouse
      developmental toxicity and 78 for rat developmental toxicity. It is concluded
      that 0.13 mgB/kg/day is the most appropriate TDI for boron, based on rat
      developmental toxicity.

PMID- 23137931
TI  - Bladder/lung cancer mortality in Blackfoot-disease (BFD)-endemic area villages
      with low (<150 MUg/L) well water arsenic levels--an exploration of the dose
      response Poisson analysis.
AB  - OBJECTIVE: To examine the analytic role of arsenic exposure on cancer mortality
      among the low-dose (well water arsenic level <150 MUg/L) villages in the
      Blackfoot-disease (BFD) endemic area of southwest Taiwan and with respect to the
      southwest regional data. METHOD: Poisson analyses of the bladder and lung cancer
      deaths with respect to arsenic exposure (MUg/kg/day) for the low-dose (<150
      MUg/L) villages with exposure defined by the village median, mean, or maximum and
      with or without regional data. RESULTS: Use of the village median well water
      arsenic level as the exposure metric introduced misclassification bias by
      including villages with levels >500 MUg/L, but use of the village mean or the
      maximum did not. Poisson analyses using mean or maximum arsenic levels showed
      significant negative cancer slope factors for models of bladder cancers and of
      bladder and lung cancers combined. Inclusion of the southwest Taiwan regional
      data did not change the findings when the model contained an explanatory variable
      for non-arsenic differences. A positive slope could only be generated by
      including the comparison population as a separate data point with the assumption
      of zero arsenic exposure from drinking water and eliminating the variable for non
      arsenic risk factors. CONCLUSION: The cancer rates are higher among the low-dose
      (<150 MUg/L) villages in the BFD area than in the southwest Taiwan region.
      However, among the low-dose villages in the BFD area, cancer risks suggest a
      negative association with well water arsenic levels. Positive differences from
      regional data seem attributable to non-arsenic ecological factors.

PMID- 23137932
TI  - Preconceptional omega-3 fatty acid supplementation on a micronutrient-deficient
      diet improves the reproductive cycle in Wistar rats.
AB  - Folic acid and vitamin B12 deficiencies are associated with high reproductive
      risks ranging from infertility to fetal structural defects. The aim of the
      present study was to examine the effects of preconceptional omega-3 fatty acid
      supplementation (eicosapentaenoic acid and docosahexaenoic acid) to a
      micronutrient-deficient diet on the reproductive cycle in Wistar rats. Female
      rats were divided into five groups from birth and throughout pregnancy: a control
      group, a folic acid-deficient (FD) group, a vitamin B12-deficient (BD) group, a
      folic acid-deficient + omega-3 fatty acid-supplemented (FDO) group and a vitamin
      B12 deficient + omega-3 fatty acid-supplemented (BDO) group. Dams were killed on
      gestation Day 20 and their ovaries and mammary glands were dissected out and
      subjected to histological examination. Maternal micronutrient deficiency (FD and
      BD groups) resulted in an abnormal oestrous cycle (P<0.001), whereas omega-3
      fatty acid supplementation (FDO and BDO groups) restored the oestrous cycle to
      normal. There were fewer corpora lutea in the ovaries of FD rats compared with
      controls. In addition, rats in both the FD and BD groups exhibited an absence of
      lactating ducts in their mammary glands compared with controls. The findings of
      the present study indicate, for the first time, that maternal micronutrient
      deficiency affects the oestrous cycle and morphology of the ovary and mammary
      glands. Omega-3 fatty acid supplementation ameliorated these effects. This may
      have implications for infertility and pregnancy outcomes. 

PMID- 23137933
TI  - Magnetic and thermal responses triggered by structural changes in the double
      perovskite Sr2YRuO6.
AB  - Among double perovskites, the interpretation of the magnetic, thermal and
      transport properties of Sr(2)YRuO(6) remains a challenge. Characterization using
      different techniques reveals a variety of features that are not understood,
      described as anomalous, and yields contradictory values for several relevant
      parameters. We solved this situation through detailed susceptibility, specific
      heat, thermal expansion and x-ray diffraction measurements, including a
      quantitative correlation of the parameters characterizing the so-called
      anomalies. The emergence of short-range magnetic correlations, surviving well
      above the long-range transition, naturally accounts for the observed
      unconventional behavior of this compound. High resolution x-ray powder
      diffraction and thermal expansion results conclusively show that the magnetic and
      thermal responses are driven by lattice changes, providing a comprehensive
      scenario in which the interplay between the spin and structural degrees of
      freedom plays a relevant role.

PMID- 23137934
TI  - Exposure to DNA is insufficient for in vitro transgenesis of live bovine sperm
      and embryos.
AB  - Transgenic mammals have been produced using sperm as vectors for exogenous DNA
      (sperm-mediated gene transfer (SMGT)) in combination with artificial
      insemination. Our study evaluated whether SMGT could also be achieved in
      combination with IVF to efficiently produce transgenic bovine embryos. We
      assessed binding and uptake of fluorescently labelled plasmids into sperm in the
      presence of different concentrations of dimethyl sulphoxide or lipofectamine.
      Live motile sperm displayed a characteristic punctuate fluorescence pattern
      across their entire surface, while uniform postacrosomal fluorescence was only
      apparent in dead sperm. Association with sperm or lipofection reagent protected
      exogenous DNA from DNase I digestion. Following IVF, presence and expression of
      episomal and non-episomal green fluorescent protein (GFP)-reporter plasmids was
      monitored in oocytes and embryos. We found no evidence of intracellular plasmid
      uptake and none of the resulting zygotes (n=96) and blastocysts were GFP positive
      by fluorescence microscopy or genomic PCR (n=751). When individual zona-free
      oocytes were matured, fertilised and continuously cultured in the presence of
      episomal reporter plasmids until the blastocyst stage, most embryos (38/68=56%)
      were associated with the exogenous DNA. Using anti-GFP immunocytochemistry (n=48)
      or GFP fluorescence (n=94), no GFP expression was detected in blastocysts. By
      contrast, ICSI resulted in 18% of embryos expressing the GFP reporter. In
      summary, exposure to DNA was an inefficient technique to produce transgenic
      bovine sperm or blastocysts in vitro.

PMID- 23137935
TI  - Correlation between moderate daily physical activity and neurocognitive
      variability in healthy elderly people.
AB  - Recent studies have reported that moderate physical activity in daily life
      contributes to maintenance of a proper state of cognitive function in elderly
      individuals. The present study investigated the validity of correlations between
      moderate physical activity and cognitive function using more objective and
      detailed assessments of both physical activity and neurocognitive function.
      Participants comprised 72 healthy elderly individuals who wore an electronic
      accelerometer during waking hours for 3 months. This device recorded the number
      of steps per day as well as the duration of each intensity level in daily life;
      levels 1-3 were the equivalent of easy-paced walking (light activity), while
      levels 4-6 corresponded to brisk walking (moderate activity). To estimate
      executive cognitive ability in healthy elderly individuals, performance
      variability of executive control was examined with a task-switching reaction time
      (RT) test measuring intra-individual variability (IIV) in RTs. In 43 consenting
      participants, functional magnetic resonance imaging (fMRI) during the task
      switching RT trial was analyzed to assess differences in brain activity patterns
      as a function of daily physical activity. Daily duration of level 4 physical
      activity correlated negatively with and significantly predicted IIV. Moreover,
      fMRI analysis confirmed that the higher physical activity group (duration of
      level 4 activity >= 26.4 min/day) showed significantly reduced age-related
      functional attenuation of prefrontal activations during the task-switching RT
      trial. The study discusses the possibility that enhancing the moderate daily
      physical activity could be helpful for lowering the rate of neurocognitive
      degradations in healthy elderly individuals.

PMID- 23137936
TI  - Temporal trends and predictors in the use of aldosterone antagonists post-acute
      myocardial infarction.
AB  - OBJECTIVES: This study explored temporal trends in the use of aldosterone
      antagonist therapy among eligible patients with post-acute myocardial infarction
      (AMI) and reduced ejection fraction and characteristics associated with use in
      clinical practice. BACKGROUND: Current guidelines recommend initiation of
      aldosterone antagonist therapy post-AMI for patients with an ejection fraction
      <=40% and heart failure or diabetes before hospital discharge, in the absence of
      contraindications. METHODS: Data from the American Heart Association's Get with
      the Guidelines-Coronary Artery Disease national database were analyzed for 81,570
      post-AMI patients from 219 hospitals between 2006 and 2009, of whom 11,255
      (13.8%) were eligible for aldosterone antagonist therapy. RESULTS: Among eligible
      patients, 1,023 (9.1%) were prescribed an aldosterone antagonist at discharge.
      Aldosterone antagonist use varied from 0% to 40% among hospitals. Patient and
      hospital characteristics independently associated with prescription of
      aldosterone antagonists were a history of diabetes, heart failure, coronary
      revascularization, and larger hospital size. Those with a history of kidney
      dysfunction, tobacco abuse, and higher ejection fraction were less likely to be
      prescribed an aldosterone antagonist. From 2006 to 2009, the use of aldosterone
      antagonists increased from 6.0% to 13.4% (p < 0.001). CONCLUSIONS: Although rates
      of aldosterone antagonist use are increasing slightly over time, the vast
      majority of AMI patients eligible for treatment fail to receive it at hospital
      discharge. The reason for this discrepancy between guideline-based therapy and
      actual prescribing patterns is unclear and should be further studied.

PMID- 23137937
TI  - The divergence between clinical guidelines and practice.

PMID- 23137938
TI  - 'So I forgot to use 1.5 line spacing! It doesn't make me a bad nurse!' The
      attitudes to and experiences of a group of Norwegian postgraduate nurses to
      academic writing.
AB  - AIM: To describe the experience of a group of postgraduate Norwegian nurses with
      academic writing and its impact on their engagement with continuing education.
      BACKGROUND: Nurses are required to be lifelong learners and increasing numbers
      are seeking further knowledge and skills for clinical practice through courses in
      institutions of higher education. In higher education they are often being
      assessed on their ability to produce an academic essay not on the development of
      their clinical competence. METHOD: A descriptive design was used, where
      participants were asked to complete in writing two open-ended statements. The
      data was then subject to inductive content analysis to extract categories and
      themes to describe the phenomenon. FINDINGS: Participants had little experience
      and were challenged by academic writing. It was perceived as difficult, time
      consuming and of little relevance to their clinical practice. CONCLUSION: There
      is disconnection between the assessment of learning in higher education and
      increased workplace competency. Rather than promoting a deep approach to learning
      educators may be creating barriers to engagement with lifelong learning through
      using traditional assessment practices. There is an imperative to develop
      assessments which allow demonstration of understanding, ability to use current
      evidence and the development of critical analytic skills for reflection on
      problems encountered in participants' work lives.

PMID- 23137939
TI  - Game changers: in the realm of ideas.

PMID- 23137940
TI  - A general path for large-scale solubilization of cellular proteins: from membrane
      receptors to multiprotein complexes.
AB  - Expression of recombinant proteins in bacterial or eukaryotic systems often
      results in aggregation rendering them unavailable for biochemical or structural
      studies. Protein aggregation is a costly problem for biomedical research. It
      forces research laboratories and the biomedical industry to search for
      alternative, more soluble, non-human proteins and limits the number of potential
      "druggable" targets. In this study we present a highly reproducible protocol that
      introduces the systematic use of an extensive number of detergents to solubilize
      aggregated proteins expressed in bacterial and eukaryotic systems. We validate
      the usefulness of this protocol by solubilizing traditionally difficult human
      protein targets to milligram quantities and confirm their biological activity. We
      use this method to solubilize monomeric or multimeric components of multi-protein
      complexes and demonstrate its efficacy to reconstitute large cellular machines.
      This protocol works equally well on cytosolic, nuclear and membrane proteins and
      can be easily adapted to a high throughput format.

PMID- 23137941
TI  - Structures of septin filaments prepared from rat brain and expressed in bacteria.
AB  - Septin forms a conserved family of cytoskeletal GTP-binding proteins that have
      diverse roles in protein scaffolding, vesicle trafficking and cytokinesis. There
      are 14 mammalian septin isoforms and these isoforms assemble into hetero
      oligomeric rod-shaped complexes and these short filaments are the basal units to
      construct higher-order structures such as longer filaments, rings, gauzes or
      hourglasses. Septin expressed in a eukaryotic expression system forms various
      structures such as bundles, sheets, helixes, and rings. Septin expressed in
      bacteria formed hexameric short filaments and single or parallel long filaments,
      but no such higher order structures were observed so far. In a previous study, we
      showed maturation-dependent localization of septin isoforms to the lipid raft
      fraction of rat brain. In this study, we attempted further purification of raft
      localized septin isoforms. Repeated cycles of extraction with high MgCl(2)
      solution and precipitation under low ionic solution were combined with several
      column procedures. The obtained fraction contained several septin isoforms and
      showed rings of bundled filaments with a diameter of ~0.4MUm. Several non-septin
      proteins were also detected in the fraction. We also attempted expression of
      septin isoforms in bacteria and found that the expressed septin complexes formed
      bundles of filaments. In addition to linear and curled filaments, circular
      bundles of thin filaments with a diameter of ~0.6MUm were also observed. These
      results suggest that the curvature of the bundles of septin filaments may be
      regulated by the regulatory factor(s) in the lipid raft.

PMID- 23137942
TI  - A plea for surgical lymph node staging in advanced prostate cancer.

PMID- 23137943
TI  - Calibration of the spring constant of cantilevers of arbitrary shape using the
      phase signal in an atomic force microscope.
AB  - The measurement of cantilever parameters is an essential part of performing a
      calibrated measurement with an atomic force microscope (AFM). The thermal motion
      method is a widely used technique for calibrating the spring constant of an AFM
      cantilever, which can be applied to non-rectangular cantilevers. Given the trend
      towards high frequency scanning, calibration of non-rectangular cantilevers is of
      increasing importance. This paper presents two results relevant to cantilever
      calibration via the thermal motion method. We demonstrate the possibility of
      using the AFM's phase signal to acquire the thermal motion. This avoids the
      challenges associated with connecting the raw photodiode signal to a separate
      spectrum analyser. We also describe how numerical calculations may be used to
      calculate the parameters needed in a thermal motion calibration of a non
      rectangular cantilever. Only accurate knowledge of the relative size of the in
      plane dimensions of the cantilever is needed in this computation. We use this
      pair of results in the calibration of a variety of rectangular and non
      rectangular cantilevers. We observe an average difference between the Sader and
      thermal motion values of cantilever stiffness of 10%.

PMID- 23137944
TI  - Nuclease-resistant DNA aptamer on gold nanoparticles for the simultaneous
      detection of Pb2+ and Hg2+ in human serum.
AB  - There has been great progress in the development of functional DNA-based sensors
      for the detection of metal ions. However, many functional DNAs are vulnerable to
      hydrolysis by nucleases in human blood. In addition, the detection methods that
      are based on DNA often exhibit interference due to the high blood concentrations
      of other ions, such as K(+) and Na(+). Therefore, we selected highly Pb(2+)
      specific DNA-aptamer sequences based on CD spectroscopy of 4 G-rich DNA sequences
      and Hg(2+)-specific T-rich DNA sequences and immobilized them on gold
      nanoparticles for the simultaneous detection of Pb(2+) and Hg(2+) in human serum.
      We used gold nanoparticles because these have a superior fluorescence-quenching
      efficiency over a broad range of wavelengths compared with other organic
      quenchers. In addition, gold nanoparticles have a stabilizing effect on the
      immobilized DNA, which makes it more resistant to degradation by nucleases than
      free DNA. As a result, even in the presence of DNase, we were able to
      simultaneously detect Pb(2+) and Hg(2+) in serum at concentrations as low as 128
      pM and 121 pM, respectively, within 10 min. These detection limits for Pb(2+) and
      Hg(2+) were 39-fold and 26.4-fold lower, respectively, than the detection limits
      that were obtained using free DNAs. Given the multi-color-fluorescence quenching
      capability of the gold nanoparticles and the possibility of developing functional
      nucleic acids for the detection of other metal ions, this study extends the
      application of oligonucleotides to a point-of-care detection system for the
      detection of multiple harmful metal ions in body fluids.

PMID- 23137946
TI  - Nonconscious emotional processing involves distinct neural pathways for pictures
      and videos.
AB  - Facial expressions are known to impact observers' behavior, even when they are
      not consciously identifiable. Relying on visual crowding, a perceptual phenomenon
      whereby peripheral faces become undiscriminable, we show that participants
      exposed to happy vs. neutral crowded faces rated the pleasantness of subsequent
      neutral targets accordingly to the facial expression's valence. Using functional
      magnetic resonance imaging (fMRI) along with psychophysiological interaction
      analysis, we investigated the neural determinants of this nonconscious preference
      bias, either induced by static (i.e., pictures) or dynamic (i.e., videos) facial
      expressions. We found that while static expressions activated primarily the
      ventral visual pathway (including task-related functional connectivity between
      the fusiform face area and the amygdala), dynamic expressions triggered the
      dorsal visual pathway (i.e., posterior partietal cortex) and the substantia
      innominata, a structure that is contiguous with the dorsal amygdala. As temporal
      cues are known to improve the processing of visible facial expressions, the
      absence of ventral activation we observed with crowded videos questions the
      capacity to integrate facial features and facial motions without awareness.
      Nevertheless, both static and dynamic facial expressions activated the
      hippocampus and the orbitofrontal cortex, suggesting that nonconscious preference
      judgments may arise from the evaluation of emotional context and the computation
      of aesthetic evaluation.

PMID- 23137945
TI  - Waves of regret: a meg study of emotion and decision-making.
AB  - Recent fMRI studies have investigated brain activity involved in the feeling of
      regret and disappointment by manipulating the feedback participants saw after
      making a decision to play certain gambles: full-feedback (regret: participant
      sees the outcomes from both the chosen and unchosen gamble) vs. partial-feedback
      (disappointment: participant only sees the outcome from chosen gamble). However,
      regret and disappointment are also characterized by differential agency
      attribution: personal agency for regret, external agency for disappointment. In
      this study, we investigate the neural correlates of these two characterizations
      of regret and disappointment using magnetoencephalography (MEG). To do this, we
      experimentally induced each emotion by manipulating feedback (chosen gamble vs.
      unchosen gamble), agency (human vs. computer choice) and outcomes (win vs. loss)
      in a fully randomized design. At the behavioral level the emotional experience of
      regret and disappointment were indeed affected by both feedback and agency
      manipulations. These emotions also differentially affect subsequent choices, with
      regret leading to riskier behavior. At the neural level both feedback and agency
      affected the brain responses associated with regret and disappointment,
      demonstrating differential localization in the brain for each. Notably, feedback
      regret showed greater brain activity in the right anterior and posterior regions,
      with agency regret producing greater activity in the left anterior region. These
      findings extend the evidence for neural activity in processing both regret and
      disappointment by highlighting for the first time the respective importance of
      feedback and agency, as well as outlining the temporal dynamics of these
      emotions.

PMID- 23137947
TI  - The consequences of different definitions for recurrence of Dupuytren's disease.
AB  - BACKGROUND: Recurrence rates are important in the evaluation of the effectiveness
      of treatment for Dupuytren's disease (DD). In the literature, recurrence rates
      vary between 0% and 100%. The definition of recurrence of DD after treatment is
      inconsistently used. The aim of this study is to review all definitions of
      recurrence after treatment of DD and to evaluate the impact of using these
      definitions on a single cohort of patients treated for DD. METHODS: A literature
      search was performed in PubMed and Embase to identify studies. Titles and
      abstracts were analysed to collect all articles that described recurrence rates
      or definitions of recurrence. Two independent reviewers selected relevant studies
      and extracted data. The different definitions of recurrence were applied on our
      data set of 66 patients. RESULTS: Of the 113 articles reporting recurrent rates
      of DD, 56 (49%) presented a definition of recurrence. We could categorise the
      definitions into three groups. By applying the different definition on our data
      set of a randomised controlled trial, the recurrence rates ranged from 2% to 86%.
      CONCLUSIONS: In the literature, different definitions of recurrence of DD are
      used and many authors failed to define recurrence. This study shows that the wide
      range of reported recurrence rates may largely be contributed by inconsistency in
      recurrence definitions. As a result, it is difficult or even impossible to
      compare recurrence rates between different treatments reported in the literature.
      The study indicates that consensus on a recurrence definition is needed.

PMID- 23137948
TI  - Brain imaging and fluid biomarker analysis in young adults at genetic risk for
      autosomal dominant Alzheimer's disease in the presenilin 1 E280A kindred: a case
      control study.
AB  - BACKGROUND: We have previously characterised functional brain abnormalities in
      young adults at genetic risk for late-onset Alzheimer's disease. To gain further
      knowledge on the preclinical phase of Alzheimer's disease, we sought to
      characterise structural and functional MRI, CSF, and plasma biomarkers in a
      cohort of young adults carrying a high-penetrance autosomal dominant mutation
      that causes early-onset Alzheimer's disease. METHODS: Between January and August,
      2010, 18-26-year-old presenilin 1 (PSEN1) E280A mutation carriers and non
      carriers from the Colombian Alzheimer's Prevention Initiative Registry in
      Medellin Antioquia, Colombia, had structural MRI, functional MRI during
      associative memory encoding and novel viewing and control tasks, and cognitive
      assessments. Consenting participants also had lumbar punctures and venepunctures.
      Outcome measures were task-dependent hippocampal or parahippocampal activations
      and precuneus or posterior cingulate deactivations, regional grey matter
      reductions, CSF Abeta(1-42), total tau and phospho-tau(181) concentrations, and
      plasma Abeta(1-42) concentrations and Abeta(1-42):Abeta(1-40) ratios. Structural
      and functional MRI data were compared using automated brain mapping algorithms
      and search regions related to Alzheimer's disease. Cognitive and fluid biomarkers
      were compared using Mann-Whitney tests. FINDINGS: 44 participants were included:
      20 PSEN1 E280A mutation carriers and 24 non-carriers. The carrier and non-carrier
      groups did not differ significantly in their dementia ratings, neuropsychological
      test scores, or proportion of apolipoprotein E (APOE) E4 carriers. Compared with
      non-carriers, carriers had greater right hippocampal and parahippocampal
      activation (p=0.001 and p<0.014, respectively, after correction for multiple
      comparisons), less precuneus and posterior cingulate deactivation (all p<0.010
      after correction), and less grey matter in several parietal regions (all p<0.002
      uncorrected and corrected p=0.009 in the right parietal search region). In the 20
      participants (ten PSEN1 E280A mutation carriers and ten non-carriers) who had
      lumbar punctures and venepunctures, mutation carriers had higher CSF Abeta(1-42)
      concentrations (p=0.008) and plasma Abeta(1-42) concentrations (p=0.01) than non
      carriers. INTERPRETATION: Young adults at genetic risk for autosomal dominant
      Alzheimer's disease have functional and structural MRI findings and CSF and
      plasma biomarker findings consistent with Abeta(1-42) overproduction. Although
      the extent to which the underlying brain changes are either neurodegenerative or
      developmental remain to be determined, this study shows the earliest known
      biomarker changes in cognitively normal people at genetic risk for autosomal
      dominant Alzheimer's disease. FUNDING: Banner Alzheimer's Foundation, Nomis
      Foundation, Anonymous Foundation, Forget Me Not Initiative, Boston University
      Department of Psychology, Colciencias, National Institute on Aging, National
      Institute of Neurological Disorders and Stroke, and the State of Arizona.

PMID- 23137950
TI  - When, where, and how does Alzheimer's disease start?

PMID- 23137951
TI  - Tracking brain amyloid-beta in presymptomatic Alzheimer's disease.

PMID- 23137949
TI  - Florbetapir PET analysis of amyloid-beta deposition in the presenilin 1 E280A
      autosomal dominant Alzheimer's disease kindred: a cross-sectional study.
AB  - BACKGROUND: Fibrillar amyloid-beta (Abeta) is thought to begin accumulating in
      the brain many years before the onset of clinical impairment in patients with
      Alzheimer's disease. By assessing the accumulation of Abeta in people at risk of
      genetic forms of Alzheimer's disease, we can identify how early preclinical
      changes start in individuals certain to develop dementia later in life. We sought
      to characterise the age-related accumulation of Abeta deposition in presenilin 1
      (PSEN1) E280A mutation carriers across the spectrum of preclinical disease.
      METHODS: Between Aug 1 and Dec 6, 2011, members of the familial Alzheimer's
      disease Colombian kindred aged 18-60 years were recruited from the Alzheimer's
      Prevention Initiative's registry at the University of Antioquia, Medellin,
      Colombia. Cross-sectional assessment using florbetapir PET was done in
      symptomatic mutation carriers with mild cognitive impairment or mild dementia,
      asymptomatic carriers, and asymptomatic non-carriers. These assessments were done
      at the Banner Alzheimer's Institute in Phoenix, AZ, USA. A cortical grey matter
      mask consisting of six predefined regions.was used to measure mean cortical
      florbetapir PET binding. Cortical-to-pontine standard-uptake value ratios were
      used to characterise the cross-sectional accumulation of fibrillar Abeta
      deposition in carriers and non-carriers with regression analysis and to estimate
      the trajectories of fibrillar Abeta deposition. FINDINGS: We enrolled a cohort of
      11 symptomatic individuals, 19 presymptomatic mutation carriers, and 20
      asymptomatic non-carriers, ranging in age from 20 to 56 years. There was greater
      florbetapir binding in asymptomatic PSEN1 E280A mutation carriers than in age
      matched non-carriers. Fibrillar Abeta began to accumulate in PSEN 1E280A mutation
      carriers at a mean age of 28.2 years (95% CI 27.3-33.4), about 16 years and 21
      years before the predicted median ages at mild cognitive impairment and dementia
      onset, respectively. (18)F florbetapir binding rose steeply over the next 9.4
      years and plateaued at a mean age of 37.6 years (95% CI 35.3-40.2), about 6 and
      11 years before the expected respective median ages at mild cognitive impairment
      and dementia onset. Prominent florbetapir binding was seen in the anterior and
      posterior cingulate, precuneus, and parietotemporal and frontal grey matter, as
      well as in the basal ganglia. Binding in the basal ganglia was not seen earlier
      or more prominently than in other regions. INTERPRETATION: These findings
      contribute to the understanding of preclinical familial Alzheimer's disease and
      help set the stage for assessment of amyloid-modifying treatments in the
      prevention of familial Alzheimer's disease. FUNDING: Avid Radiopharmaceuticals,
      Banner Alzheimer's Foundation, Nomis Foundation, Anonymous Foundation, Forget Me
      Not Initiative, Colciencias, National Institute on Aging, and the State of
      Arizona.

PMID- 23137952
TI  - Sex differences in hypertension-related renal and cardiovascular diseases in
      Italy:  the I-DEMAND study.
AB  - AIM: The aim of this study is to evaluate the differences in the prevalence of
      chronic kidney disease (CKD) and of cardiovascular risk factors and diseases
      between men and women participating in the Italy Developing Education and
      awareness on MicroAlbuminuria in patients with hyperteNsive Disease (I-DEMAND)
      study. METHODS: This is an observational, cross-sectional, multicenter study
      aimed at assessing prevalence and correlates of CKD among Italian hypertensive
      patients attending out-patient referral clinics. CKD was defined as glomerular
      filtration rate (GFR) less than 60 ml/min per 1.73 m(2) [Modification of Diet in
      Renal Disease (MDRD) study equation and Chronic Kidney Disease Epidemiology
      Collaboration (CKD-EPI) equation] and/or urine albumin-to-creatinine ratio of at
      least 2.5 mg/mmol in men and of at least 3.5 mg/mmol in women or both. Left
      ventricular hypertrophy (LVH) was diagnosed by either ECG or echocardiography.
      RESULTS: A total of 3558 study patients with renal data available were considered
      for this analysis: mean age was 61 +/- 4 years and 37% had diabetes mellitus.
      Female patients (n = 1636, 46%) were older, with a greater prevalence of obesity
      and lower prevalence of smoking. The prevalence of concomitant coronary artery
      and peripheral artery diseases, but not of hypertension, diabetes mellitus, or
      heart failure, was lower in women than in men. The overall prevalence of
      albuminuria (21 vs. 32%; P = 0.001) and of microalbuminuria (16 vs. 23%; P =
      0.001) was lower in women than in men. In women the prevalence of a reduced GFR
      estimated by both MDRD (33 vs. 21%; P = 0.001) and CKD-EPI equations (32 vs. 23%;
      P = 0.001) was higher than in men. CKD prevalence was similar in women and men
      (44 vs. 41%; P = 0.095 and 43 vs. 43%; P = 0.475, respectively, when MDRD and CKD
      EPI eGFR estimations were used). The prevalence of LVH (diagnosed by either ECG
      or echocardiography) was similar in men and women (18 vs. 20%; P = 0.12).The main
      independent determinants of CKD were age, glycemia, uricemia, pulse pressure,
      hypertension duration, and previous cardiovascular diseases in men, and
      increasing age, glycemia, uricemia, pulse pressure, and a lower BMI in women.
      CONCLUSION: Renal abnormalities are present in a significant number of female
      hypertensive patients attending hypertension clinics. Prevalence of reduced eGFR
      and of microalbuminuria, associated risk factors, and clinical conditions are
      different between men and women, suggesting the need to develop specific
      therapeutic strategies to prevent renal dysfunction and reduce associated
      morbidity and mortality.

PMID- 23137953
TI  - Association between urinary albumin excretion and both central and peripheral
      blood pressure in subjects with insulin resistance.
AB  - BACKGROUND: Central blood pressure (cBP) predicts cardiovascular events.
      Regarding subclinical organ damage, the relationship between urinary albumin
      excretion (UAE) and cBP is rather unknown. OBJECTIVE: We aimed to determine
      whether cBP is related to UAE, and if this relationship is stronger than that
      observed with peripheral blood pressure (pBP). METHODS: Three hundred and twenty
      four hypertensives (61% men, aged 65 +/- 10 years) with insulin-resistance (77%
      diabetics; 23% nondiabetics with metabolic syndrome) were studied. Office pBP and
      cBP (radial applanation tonometry) were determined. UAE (albumin/creatinine) was
      averaged from three first-morning-void urine samples. Differences between
      patients with/without microalbuminuria, and the relationship between UAE and both
      pBP and cBP were analyzed. The strength of such relationship (cBP vs. pBP) was
      compared using a noninferiority test. RESULTS: Microalbuminuria was detected in
      25% of all patients. After age-adjustment and sex-adjustment, both central and
      peripheral SBP and pulse pressure (PP) (mmHg) were higher in microalbuminurics
      than in normoalbuminurics [central SBP (cSBP): 130 +/- 20 vs. 124 +/- 19;
      peripheral (pSBP): 147 +/- 22 vs. 139 +/- 20; central pulse pressure (cPP): 52 +/
      15 vs. 47 +/- 14; peripheral pulse pressure (pPP): 67 +/- 16 vs. 62 +/- 16, P <
      0.05 for all]. Partial correlation coefficients (age-adjusted and sex-adjusted)
      between blood pressure (BP) and UAE were 0.175 for cSBP, 0.143 for pSBP, 0.124
      for cPP (P < 0.05 for all), and 0.092 for pPP (P = 0.117). Neither cBP nor pBP
      were superior to each other in their association with UAE or with
      microalbuminuria. Comparisons between cBP and pBP by means of noninferiority
      tests revealed no differences in the magnitude of correlation coefficients (P =
      0.265 for SBP; P = 0.212 for PP), or differences in means between patients
      with/without microalbuminuria (P = 0.327 for SBP; P = 0.054 for PP). CONCLUSION:
      Although cBP is related with UAE, this relationship is not superior to that of
      office peripheral BP.

PMID- 23137954
TI  - The Nigerian antihypertensive adherence trial:  a community-based randomized
      trial.
AB  - BACKGROUND: Research in industrialized countries has demonstrated that a key
      factor limiting the control of hypertension is poor patient adherence and that
      the most successful interventions for long-term adherence employ multiple
      strategies. Very little data exist on this question in low-income countries,
      wherein medication-taking behavior may be less well developed. METHOD: We
      conducted a treatment adherence trial of 544 patients [mean age ~63 years, mean
      blood pressure (BP) ~168/92 mmHg] with previously untreated hypertension in urban
      and rural Nigeria. Eligible participants were randomized to one of two arms:
      clinic management only, or clinic management and home visits. Both interventions
      included three elements: a community based, nurse-led treatment program with
      physician backup; facilitation of clinic visits and health education; and the use
      of diuretics and a beta blocker as needed. After initial diagnosis, the
      management protocol was implemented by a nurse with physician backup.
      Participants were evaluated monthly for 6 months. RESULTS: Medication adherence
      was assessed with pill count and urine testing. Drop-out rates, by treatment
      group, ranged from 12 to 28%. Among participants who completed the 6-month trial,
      overall adherence was high (~77% of participants took >98% of prescribed pills).
      Adherence did not differ by treatment arm, but was better at the rural than the
      urban site and among those with higher baseline BP. Hypertension control (BP
      <140/90 mmHg) was achieved in approximately 66% of participants at 6 months.
      CONCLUSION: This community-based intervention confirms relatively modest default
      rates compared with industrialized societies, and suggests that medication
      adherence can be high in developing world settings in clinic attenders.

PMID- 23137955
TI  - Polydatin ameliorates renal injury by attenuating oxidative stress-related
      inflammatory responses in fructose-induced urate nephropathic mice.
AB  - A series of studies have recently demonstrated that the oxidative stress, nuclear
      factor-kappa B (NF-kappaB) activation and the subsequent coordinated inflammatory
      responses played an important role in the pathogenesis of urate nephropathy (UN).
      Polydatin has been suggested to have the properties of anti-oxidative, anti
      inflammatory and nephroprotective effects. However, the possible protective and
      beneficial effects of polydatin on UN are not fully elucidated. Therefore, we
      investigated the potential beneficial effects and possible mechanisms of
      polydatin on UN. In this study, polydatin showed inhibitory activities on
      xanthine oxidase to repress the level of serum uric acid in vivo and in vitro.
      Further investigations revealed that polydatin displayed little toxic effects and
      significantly ameliorated the renal function in fructose-induced UN mice. The
      nephroprotective activities of polydatin was not only due to the effects on
      remarkably attenuating the oxidative stress induced by uric acid, but also on
      markedly suppressing the oxidative stress-related inflammatory cascade, including
      decreasing the expressions of NF-kappaB p65, COX-2 and iNOS proteins and
      inhibiting the productions of TNF-alpha, PGE(2) and IL-1beta. These findings
      elucidated that polydatin exhibited prominent nephroprotective activities and low
      toxic effects.

PMID- 23137956
TI  - High-dose sodium selenite toxicity cannot be prevented by the co-administration
      of pharmacological levels of epigallocatechin-3-gallate which in turn aggravates
      the toxicity.
AB  - Selenium, an essential trace element, can also be toxic at higher levels of
      exposure. Several lines of evidence show epigallocatechin-3-gallate (EGCG), a
      predominant component of green tea catechins with numerous health benefits, can
      ameliorate the toxicity of many agents. A proof-in-principle experiment was
      conducted to determine if EGCG would ameliorate sodium selenite-induced growth
      suppression. Mice were intraperitioneally injected with selenite once daily for
      five days at a dose of 3 mg Se/kg, which fully suppressed animal growth but did
      not cause death. Surprisingly the co-administration of the selenite and nontoxic
      doses of EGCG (10, 20 and 40 mg/kg, intraperitioneally) resulted in the mortality
      of treated mice in a dose and time-dependent manner (33.3%, 100% and 100%,
      respectively). EGCG-selenite induced lethality did not result from enhanced
      selenium accumulation but appeared to involve the suppression of a selenite
      induced adaptive response as evidenced by hepatic glutathione S-transferase
      activity. While EGCG has been reported to ameliorate the toxicity of some agents,
      the induction of mortality by combined treatment with pharmacological doses of
      selenium and EGCG is a previously unrecognized synergism that must be considered
      not only in the remediation of high environmental selenium exposures but also in
      the development of pharmaceuticals and nutriceuticals.

PMID- 23137957
TI  - Dietary exposure to mycotoxins and health risk assessment in the second French
      total diet study.
AB  - Mycotoxins are produced in plants by micro-fungi species, and naturally
      contaminated the food chain. In the second French total diet study (TDS),
      mycotoxins were analyzed in 577 food samples collected in mainland France to be
      representative of the population diet and prepared ((as consumed)). Highest mean
      concentrations were found in wheat and cereal-based products (bread, breakfast
      cereals, pasta, pastries, pizzas and savoury pastries...). Exposure of adult and
      child populations was assessed by combining national consumption data with
      analytical results, using lowerbound (LB) and upperbound (UB) assumptions for
      left-censorship management. Individual exposures were compared with available
      health-based guidance values (HBGV). Only the exposure to deoxynivalenol (DON)
      and its acetylated derivatives was found to significantly exceed the HBGV in LB
      in adults (0.5% [0.1; 0.8]) and children (5% [4; 6]). HBGV was exceeded in UB
      only for T-2 and HT-2 toxins by, respectively, 0.2% [0.02; 0.05] and 4% [3; 5] of
      adults, and 11% [9; 12] and 35% [32; 37] of children. Although the exposures
      assessed were generally lower than the previous French TDS, the results indicated
      a health concern for trichothecenes and a need to reduce dietary exposure as well
      as analytical limits.

PMID- 23137958
TI  - Compositional uniformity, domain patterning and the mechanism underlying nano
      chessboard arrays.
AB  - We  propose that systems exhibiting compositional patterning at the nanoscale, so
      far assumed to be due to some kind of ordered phase segregation, can be
      understood instead in terms of coherent, single phase ordering of minority
      motifs, caused by some constrained drive for uniformity. The essential features
      of this type of arrangement can be reproduced using a superspace construction
      typical of uniformity-driven orderings, which only requires the knowledge of the
      modulation vectors observed in the diffraction patterns. The idea is discussed in
      terms of a simple two-dimensional lattice-gas model that simulates a binary
      system in which the dilution of the minority component is favoured. This simple
      model already exhibits a hierarchy of arrangements similar to the experimentally
      observed nano-chessboard and nano-diamond patterns, which are described as
      occupational modulated structures with two independent modulation wavevectors and
      simple step-like occupation modulation functions.

PMID- 23137959
TI  - Pilot study comparing sepsis management with and without electronic clinical
      practice guidelines in an academic emergency department.
AB  - BACKGROUND: Sepsis is a potentially life-threatening condition that requires
      urgent management in an Emergency Department (ED). Evidence-based guidelines for
      managing sepsis have been developed; however, their integration into routine
      practice is often incomplete. Care maps may help clinicians meet guideline
      targets more often. OBJECTIVES: To determine if electronic clinical practice
      guidelines (eCPGs) improve management of patients with severe sepsis and septic
      shock (SS/SS). METHODS: The impact of an eCPG on the management of patients
      presenting with SS/SS over a 3-year period at a tertiary care ED was evaluated
      using retrospective case-control design and chart review methods. Cases and
      controls, matched by age and sex, were chosen from an electronic database using
      physician sepsis diagnoses. Data were compared using McNemar tests or paired t
      tests, as appropriate. RESULTS: Overall, 51 cases and controls were evaluated;
      the average age was 62 years, and 60% were male. eCPG patients were more likely
      to have a central venous pressure and central venous oxygen saturation measured;
      however, lactate measurement, blood cultures, and other investigations were
      similarly ordered (all p > 0.05). The administration of antibiotics within 3 h
      (63% vs. 41%; p = 0.03) and vasopressors (45% vs. 20%; p = 0.02) was more common
      in the eCPG group; however, use of corticosteroids and other interventions did
      not differ between the groups. Overall, survival was high and similar between
      groups. CONCLUSION: A sepsis eCPG experienced variable use; however, physicians
      using the eCPG achieved more quality-of-care targets for SS/SS. Strategies to
      increase the utilization of eCPGs in Emergency Medicine seem warranted.

PMID- 23137960
TI  - Therapeutic approach in patients with a floating thrombus in the right heart.
AB  - BACKGROUND: The occurrence of a floating thrombus in the right heart, although
      rare, is a life-threatening condition requiring a specific approach. In most
      cases, these thrombi are a result of embolization from deep venous thrombosis,
      and have lodged temporarily in the right heart. The management of this condition
      is variable, depending on whether or not there is a thrombus entrapped within a
      foramen ovale (FO). OBJECTIVES: To present the management of 2 patients with a
      free-floating thrombus in the right heart, and a third patient with an entrapped
      thrombus in the FO. CASE REPORTS: Two patients with a free-floating thrombus in
      the right atrium who were treated with thrombolytic therapy had an immediate
      excellent outcome. The patient with a thrombus entrapped within the FO was
      scheduled for surgical removal of the thrombus due to an unacceptable risk of
      systemic embolization if treated with thrombolytic and anticoagulant therapy.
      Unfortunately, he developed an ischemic stroke on the fifth day of presentation,
      just a few hours before the scheduled surgery, despite meticulous monitoring of
      continuous heparin infusion with activated partial thromboplastin time.
      CONCLUSION: Thrombolytic therapy is recommended in patients with a free-floating
      thrombus in the right heart. However, in patients with a thrombus entrapped
      within an FO, delaying surgical removal of the thrombus may be deleterious due to
      unpredictable systemic embolization.

PMID- 23137961
TI  - Toxic CO-ingestions in intentional carbon monoxide poisoning.
AB  - BACKGROUND: Intentional carbon monoxide (CO) poisoning is responsible for two
      thirds of the deaths from CO poisoning in this country and an estimated 15,000
      Emergency Department visits annually. OBJECTIVES: In an attempt to optimize
      medical management of such patients, this study was conducted to examine the
      frequency and types of toxic co-ingestions that may accompany CO inhalation.
      METHODS: Records of all patients treated with hyperbaric oxygen for acute,
      intentional CO poisoning at a regional referral center for hyperbaric medicine in
      Seattle from 1980 to 2005 were reviewed. For those where co-ingestions were
      identified, information about type of poison(s) and results of toxicology screens
      was recorded and analyzed. RESULTS: Over the 25-year period examined, 433
      patients were treated for intentional CO poisoning and records were available for
      426. Of those, 188 (42%) had ingested one or more poisons in addition to CO.
      Ethanol was most common, but a wide variety of other drug classes were also
      identified. Toxicology screening studies of some type were performed in 49
      patients. CONCLUSIONS: Toxic co-ingestions seem to be relatively common in
      patients treated for intentional CO poisoning. For this reason, providers should
      be vigilant and open to clinical signs that can't be explained with CO exposure
      alone, and ready to treat clinical issues that arise from co-ingestions.

PMID- 23137962
TI  - The 112 emergency telephone service.

PMID- 23137963
TI  - Reprofiled drug targets ancient protozoans: drug discovery for parasitic
      diarrheal diseases.
AB  - Recently, we developed a novel automated, high throughput screening (HTS)
      methodology for the anaerobic intestinal parasite Entamoeba histolytica. We
      validated this HTS platform by screening a chemical library containing US Food
      and Drug Administration (FDA)-approved drugs and bioactive compounds. We
      identified an FDA-approved drug, auranofin, as most active against E. histolytica
      both in vitro and in vivo. Our cell culture and animal studies indicated that
      thioredoxin reductase, an enzyme involved in reactive oxygen species
      detoxification, was the target for auranofin in E. histolytica. Here, we discuss
      the rationale for drug development for three parasites which are major causes of
      diarrhea worldwide, E. histolytica, Giardia lamblia and Cryptosporidium parvum
      and extend our current finding of antiparasitic activity of auranofin to
      Entamoeba cysts, G. lamblia and C. parvum. These studies support the use of HTS
      assays and reprofiling FDA-approved drugs for new therapy for neglected tropical
      diseases.

PMID- 23137964
TI  - Oligosaccharide structure determines prebiotic role of beta-galactomannan against
      Salmonella enterica ser. Typhimurium in vitro.
AB  - Prebiotics and probiotics are considered natural alternatives to dietary
      antibiotics in animal production. Plant extracts and yeast cell walls are mannose
      rich products that can be used as substrate for adhesion of Gram-negative
      bacteria. We assessed whether the structure of these saccharides is relevant to
      develop their role as prebiotics and therefore, their suitability to be used as
      alternatives to antibiotics to prevent intestinal infections in pigs. The
      prebiotic functionality of beta-galactomannan (betaGM), mannanoligosaccharide
      from yeast Saccharomyces cerevisiae (Mannan SC) and monosaccharide D-Mannose were
      studied in porcine intestinal epithelial cells (IPI-2I) challenged with
      Salmonella enterica ser. Typhimurium. Results showed that in vitro challenge with
      Salmonella induces the secretion of proinflammatory cytokine IL6 and chemokine
      CXCL8 compared with control without infection. Both betaGM and Mannan SC,
      attenuate Salmonella-induced secretion of IL6 and CXCL8. Interestingly, cells
      treated with D-mannose showed similar levels of proinflammatory IL6 and CXCL8
      compared with the control of infection. These data suggest that prebiotic role of
      betaGM is related to its oligosaccharide structure.

PMID- 23137966
TI  - Targeting aberrant colon cancer-specific DNA methylation with lipoteichoic acid
      deficient Lactobacillus acidophilus.
AB  - Pathogenic autoinflammatory responses triggered by dysregulated microbial
      interactions may lead to intestinal disorders and malignancies. Previously, we
      demonstrated that a lipoteichoic acid (LTA)-deficient Lactobacillus acidophilus
      strain, NCK2025, ameliorated inflammation-induced colitis, significantly reduced
      the number of polyps in a colonic polyposis cancer model and restored
      physiological homeostasis in both cases. Nonetheless, the regulatory signals
      delivered by NCK2025 to reprogram the gastrointestinal microenvironment, and thus
      resist colonic cancer progression, remain unknown. Accumulating evidence suggest
      that epigenetic changes, in the presence and absence of pathogenic inflammation,
      can result in colorectal cancer (CRC). To test possible epigenetic modifications
      induced by NCK2025, the expression of epigenetically regulated, CRC-associated
      genes was measured with and without bacterial treatment. In vivo and in vitro,
      NCK2025 enhanced the expression of tumor suppressor genes that may regulate CRC
      development. Therefore, differential epigenetic regulation of CRC-related genes
      by NCK2025 represents a potential therapy against colitis-associated and sporadic
      CRC.

PMID- 23137967
TI  - The time course of perceptual grouping in natural scenes.
AB  - Visual perception starts with localized filters that subdivide the image into
      fragments that undergo separate analyses. The visual system has to reconstruct
      objects by grouping image fragments that belong to the same object. A widely held
      view is that perceptual grouping occurs in parallel across the visual scene and
      without attention. To test this idea, we measured the speed of grouping in
      pictures of animals and vehicles. In a classification task, these pictures were
      categorized efficiently. In an image-parsing task, participants reported whether
      two cues fell on the same or different objects, and we measured reaction times.
      Despite the participants' fast object classification, perceptual grouping
      required more time if the distance between cues was larger, and we observed an
      additional delay when the cues fell on different parts of a single object.
      Parsing was also slower for inverted than for upright objects. These results
      imply that perception starts with rapid object classification and that rapid
      classification is followed by a serial perceptual grouping phase, which is more
      efficient for objects in a familiar orientation than for objects in an unfamiliar
      orientation.

PMID- 23137965
TI  - The influence of commensal bacteria-derived signals on basophil-associated
      allergic inflammation.
AB  - Commensal bacteria that colonize mammalian mucosal surfaces are reported to
      influence T helper type 2 (TH 2) cytokine-dependent inflammation and
      susceptibility to allergic disease. However, the mechanisms that underlie these
      observations are only beginning to be understood. We recently utilized studies of
      murine model systems and atopic patient populations to elucidate a mechanism by
      which commensal bacteria-derived signals limit serum immunoglobulin E levels,
      influence basophil development and steady-state circulating basophil populations
      and regulate basophil-associated TH 2 cell responses and allergic inflammation.
      In this addendum, we summarize the findings of our recent work and other
      developments in the field, discuss the broader implications of these findings and
      generate new hypotheses regarding our understanding of host-commensal
      relationships. These areas of investigation may be applicable to the development
      of new preventative or therapeutic approaches to reduce the burden of allergic
      disease.

PMID- 23137968
TI  - Covert painting simulations influence aesthetic appreciation of artworks.

PMID- 23137969
TI  - Looking inward: shifting attention within working memory representations alters
      emotional responses.
AB  - Selective attention plays a fundamental role in emotion regulation. To date,
      research has examined individuals' use of selective attention to regulate
      emotional responses during stimulus presentation. In the present study, we
      examined whether selective attention can be used to regulate emotional responses
      during a poststimulus period when representations are active within working
      memory (WM). On each trial, participants viewed either a negative or a neutral
      image. After the offset of the image, they maintained a representation of it in
      WM and were cued to focus their attention on either neutral or arousing aspects
      of that representation. Results showed that, relative to focusing on an arousing
      portion of a negative-image representation within WM, focusing on a neutral
      portion of the representation reduced both self-reported negative emotion and the
      late positive potential, a robust neural measure of emotional reactivity. These
      data suggest that selective attention can alter emotional responses arising from
      affective representations active within WM.

PMID- 23137970
TI  - Impact of stigma on the quality of life of patients with refractory epilepsy.
AB  - PURPOSE: To assess the impact of perceived stigma on the quality of life of
      Bulgarian patients with refractory epilepsy. METHODS: We studied 70 adult
      patients with refractory epilepsy, without cognitive impairment, progressive
      somatic, neurological disease or recent seizures, and 70 patients with
      pharmacosensitive epilepsy. All participants completed a 3-item stigma scale, the
      patients with refractory epilepsy also completed a Health Related Quality of Life
      measure (the QOLIE-89). RESULTS: The patients with refractory epilepsy had a mean
      disease duration 25.1+/-1.3 years. 40.0% of patients (+/-5.9) had symptomatic
      epilepsy. Seventeen patients (24.2%+/-5.1) had partial seizures, 16 (22.8%+/-5.0)
      had generalized seizures and 37 (52.9+/-6.0) had a mixture of partial and
      generalized seizures. Most participants had several seizures per week (45.7%) or
      month (30.0%) despite the fact that 90% were taking combination antiepileptic
      drug treatment. We found perceived stigma in 43.6% of patients with refractory
      epilepsy, and 28.7% self-reported severe stigmatization. Only 4 (5.7%) patients
      with pharmacosensitive epilepsy reported stigmatization which was mild or
      moderate in all cases. Perceived stigma had a negative impact on the overall
      score of the QOLIE-89 (T-score 47.8), as well as on all subscales of QOLIE-89,
      with the exception of "change in health" and "sexual relations". Patients with
      refractory epilepsy reporting stigmatization most commonly had very low and low
      scores on the subscales "health perceptions" (82.9%), "emotional well-being"
      (71.5%), "memory" (63.4%) and "health discouragement" (62.5%). There was a
      negative correlation of all QOLIE-89 subscales with perceived stigma severity.
      CONCLUSION: All aspects of the quality of life of Bulgarian patients with
      refractory epilepsy correlate negatively with the severity of perceived stigma.

PMID- 23137971
TI  - Occurrence of pesticides in transboundary aquifers of North-eastern Greece.
AB  - A five-year groundwater monitoring program undertaken in Evros (north-east
      Greece), showed a diversification in the levels of pesticide residues detected in
      adjacent transboundary aquifers. During the first two years 37 wells, including
      irrigation, drinking water and artesian wells were monitored while the next three
      years the survey was focused on the 11 most contaminated wells. The presence of
      pesticide residues was also monitored in the phreatic horizon (shallow
      groundwater) of four experimental boreholes drilled in the respective margins of
      four fields. Among the compounds found alachlor, metolachlor, atrazine,
      desethylatrazine (DEA), desisopropylatrazine (DIA) and caffeine were constantly
      detected. Pesticide concentrations were much lower (up to 1.54 MUg/L) in the
      water of the monitored drinking water wells (deep groundwater aquifers) compared
      to those found in the phreatic horizon (experimental boreholes) of the respective
      areas (up to 5.20 MUg/L). DEA to atrazine concentration ratios (DAR) determined
      for the phreatic horizon of the three boreholes and respective wells were lower
      than 1, indicating that preferential flow was the cause of the fast downward
      movement of atrazine to the phreatic horizon. In contrast the DAR for the fourth
      borehole and the adjacent well were greater than 1 indicating the absence of
      preferential flow of atrazine. Catabolic processes of the soil converted atrazine
      to DEA which is more mobile than atrazine itself through chromatographic
      (darcian) flow. This differential behavior of pesticides in adjacent aquifers (3
      km) was further investigated by determining the apparent age of water in the two
      wells. The apparent age of the water present in the first aquifer was 21.7 years
      whereas the apparent age of that in the second aquifer was approximately 1.2
      years. The faster replenishing rate of the latter is an indication that this
      aquifer is very vulnerable to contamination with pollutants present in the
      infiltrated soil water.

PMID- 23137972
TI  - Simultaneous analysis of non-steroidal anti-inflammatory drugs and estrogenic
      hormones in water and wastewater samples using gas chromatography-mass
      spectrometry and gas chromatography with electron capture detection.
AB  - Non-steroidal anti-inflammatory drugs are the group of pharmaceuticals that is
      most often found in the environment, whereas estrogenic hormones are considered
      to be potent endocrine disruptors. However, the fate and persistence of these
      compounds in the environment are still unclear. In this study we propose two
      approaches for determining these compounds in environmental water samples: GC-MS
      using time windows and operating in selected ion-monitoring mode (SIM) and, for
      the first time, gas chromatography with electron capture detection (GC-ECD). The
      identification criteria of both methods fulfilled the requirements of Directive
      2002/657/EC. The use of time windows improved the sensitivity of GC-MS
      measurements. In GC-MS analysis the pharmaceuticals were determined as
      trimethylsilyl, in GC-ECD as pentafluoropropionyl derivatives. The influence of
      such parameters as the type of reagent, type of solvent, reaction time, reaction
      temperature and microwave irradiation in a household microwave oven on the
      efficacy of silylation was investigated. Derivatization using N,O
      bis(trimethylsilyl)trifluoroacetamide (BSTFA) and 1% trimethylchlorosilane (TMCS)
      in pyridine (1:1, v/v) for 30 min in 60  degrees C was found to be optimal.
      Optimization of the solid phase extraction procedure (SPE) confirmed that the
      application of Oasis HLB cartridges, the acidification of loading samples to pH2
      and the use of methanol as eluent gave the best absolute recoveries (ARs) of the
      target compounds. The following ARs of all the compounds were achieved: 58.2
      106.8% in influent wastewater, 77.8-103.4% in effluent wastewater and 81.2-101.9%
      in surface water samples. Validation of the SPE-GC-MS method enables 13
      pharmaceuticals to be determined with MDLs between 3.3 and 343.6 ng/L, depending
      on the analytes and matrices. GC-ECD analysis enables the determination of 6
      pharmaceuticals in surface water samples with MDLs between 0.7 and 5.4 ng/L. The
      proposed methods were successfully used for analyzing selected pharmaceuticals in
      wastewaters and river waters in Poland.

PMID- 23137973
TI  - Assessing anthropogenic contamination in surface sediments of Niger Delta,
      Nigeria with fecal sterols and n-alkanes as indicators.
AB  - The occurrence of sterols and n-alkanes in surface sediments from rivers and
      canals in the Niger Delta, Nigeria, determined with a gas chromatography-mass
      spectrometry method, was used to assess the impacts of anthropogenic activities
      in the area. The concentrations of total sterols (?8Sterol) and n-alkanes (?28n
      alkane) in the sediments ranged from 133 to 2040 ng/g and 474 to 79,200 ng/g,
      respectively. An evaluation of the source diagnostic indices indicated that
      petroleum related sources (petrogenic) were the main contributor of n-alkanes in
      the samples, with minor contribution from higher plants waxes (biogenic), while
      the sterols were mainly of biogenic origin. The ratio of alpha
      cholestanone/(alpha-cholestanone+beta-cholestanone), a commonly used source
      diagnostic index, implicated no fecal contamination in most of the sediment
      samples under investigation. These results have established the occurrence of
      anthropogenic contamination in Niger Delta sediments with significant
      contributions from petrogenic sources.

PMID- 23137974
TI  - Synoptic patterns and air mass transport during ozone episodes in northwestern
      Iberia.
AB  - High levels of ozone are frequently measured at the Galicia (NW Iberian
      Peninsula) air quality monitoring stations from March to October. However, there
      have been very few studies on surface ozone in the northwestern Iberian
      Peninsula, most likely because the climate of this region is not favourable to
      photochemical ozone generation. The occurrence of these episodes may be related
      to either local-scale photochemical pollution or regional-scale transport from
      other polluted regions. In addition, high ozone episodes usually are developed
      under specific synoptic conditions. The main purposes of this study are to
      characterise the atmospheric conditions that lead to the ozone episodes in this
      region and to identify possible advection paths of ozone and precursors. A
      surface hourly ozone dataset (2002-2007) measured at rural sites in Galicia was
      analysed to identify high ozone episodes together with their associated synoptic
      patterns using a subjective classification with 23 different synoptic types. The
      synoptic weather patterns revealed that most of the episodes occur with high
      surface pressures centred over the British Isles and/or Central Europe while a
      high-altitude anticyclonic ridge crosses the Peninsula from North Africa, causing
      easterly or southeasterly winds. This analysis was completed with 3-day backward
      air mass trajectories obtained with HYSPLIT to assess the contribution of long
      range transport, resulting in the following main routes: Mediterranean
      Peninsular, South Atlantic-Portuguese, local and French-Cantabric.

PMID- 23137975
TI  - Assessment of 7Be content in precipitation in a South American semi-arid
      environment.
AB  - There are two naturally occurring radiogenic isotopes of beryllium, 7Be and 10Be.
      These are produced when cosmic radiation interacts with oxygen and nitrogen in
      the atmosphere. After production, these radionuclides are input to ecosystems
      through wet and dry deposition. In recent years 7Be and 10Be have proved to be
      powerful tools for studying dynamic processes that occur on the surface of the
      earth. We measured the 7Be content in precipitation at a semiarid location in
      central Argentina. From November 2006 to March 2009, 68 precipitation events were
      collected. Measured 7Be content ranged from 0.7+/-0.4 Bq L-1 to 3.2+/-0.7 Bq L-1,
      with a mean of 1.7 Bq L-1 +/-0.6 Bq L-1. Beryllium-7 content of rainfall did not
      show clear relationships with amount of rainfall (mm), mean intensity (mm h-1) or
      duration (h-1), or elapsed time between events (day). The general results
      indicate that for the typical range of precipitation there was no atmospheric
      washout and that the reload of the atmosphere is not a relevant factor, but when
      the amount of precipitation is very high washout may occur. On the other hand,
      when the 7Be content was measured during single rain events, a high content of
      this radionuclide was found to be associated with very low rainfall intensity (~3
      mm h-1), this suggests that rain intensity could affect the 7Be content. Using
      all data, a good linear relationship between 7Be deposition and rain magnitude
      was obtained (r2=0.82, p<0.0001). Because of this, the slope of this linear
      regression equation may be applied as a tool for tracing environmental processes
      that affect the surface of the earth. We can do this by directly estimating
      erosion/sedimentation processes using 7Be or by estimating the input of 10Be in
      the environment with the aim to evaluate land degradation phenomena.

PMID- 23137976
TI  - Genotoxic effects of copper oxide nanoparticles in Neuro 2A cell cultures.
AB  - Copper oxide nanoparticles (CuO NPs) are used for their biocide potential however
      they were also shown to be highly toxic to mammalian cells. Therefore, the
      effects of CuO NPs should be carefully investigated to determine the most
      sensitive processes for CuO NP toxicity. In this study, the genotoxicity of CuO
      NPs was investigated in vitro, using the mouse neuroblastoma cell line Neuro-2A.
      Genotoxic effects related to DNA fragmentation, DNA methylation and chromosomal
      damage, as well as lipid peroxidation, were investigated and compared to
      cytotoxic effects, measured by the mitochondrial reduction of 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide into formazan. Based on
      mitochondrial activity, CuO NPs were found to be cytotoxic. At the highest
      concentration tested (400 mg l-1), 63% of cell viability was found in Neuro-2A
      cells after 24 h of treatment to CuO NPs. CuO NPs were also found to induce DNA
      fragmentation, lipid peroxidation and micronucleus formation. The micronucleus
      assay was the most sensitive to evaluate CuO NP genotoxicity and micronucleus
      frequency was increased significantly at 12.5 mg l-1 CuO NPs after 24h of
      treatment. At this concentration, no significant change of cell viability was
      found using the mitochondrial activity assay. These results highlight the
      important risk of genotoxic effects of CuO NPs and show that genotoxicity assays
      are a sensitive approach to evaluate the risk of CuO NP toxicity.

PMID- 23137977
TI  - pH-dependent aquatic criteria for 2,4-dichlorophenol, 2,4,6-trichlorophenol and
      pentachlorophenol.
AB  - Due to their agricultural as well as industrial uses, 2,4-dichlorophenol (2,4
      DCP), 2,4,6-trichlorophenol (2,4,6-TCP), and pentachlorophenol (PCP) are
      ubiquitous in the environment and recognized as priority pollutants in many
      countries. In this study, effects of pH on toxicity to the crustacean Daphnia
      magna and the alga Scenedesmus obliquus were investigated. Combined published
      toxicity data of the three chlorophenols along with; relationships between
      toxicity and pH reported here were used to establish pH-dependent water quality
      criteria (WQC). The WQC expressed as a function of pH, also considered intra
      species variation and proportions of taxonomic groups. At pH 7.8, the recommended
      acute exposure water quality criteria (WQC) were 286.2 MUg 2,4-DCP/l, 341.5 MUg
      2,4,6-TCP/l and 11.4 MUg PCP/l. The recommended chronic exposure WQC were 16.3
      MUg 2,4-DCP/l, 54.6 MUg 2,4,6-TCP/land 3.9 MUg PCP/l.

PMID- 23137978
TI  - Incidental phosphorus and nitrogen loss from grassland plots receiving chemically
      amended dairy cattle slurry.
AB  - Chemical amendment of dairy cattle slurry has been shown to effectively reduce
      incidental phosphorus (P) losses in runoff; however, the effects of amendments on
      incidental nitrogen (N) losses are not as well documented. This study examined P
      and N losses in runoff during three simulated rainfall events 2, 10 and 28 days
      after a single application of unamended/chemically amended dairy cattle slurry.
      Twenty-five hydraulically isolated plots, each measuring 0.9 m by 0.4 m and
      instrumented with runoff collection channels, were randomly assigned the
      following treatments: (i) grass-only, (ii) slurry-only (the study-control), (iii)
      slurry amended with industrial grade liquid alum comprising 8% Al2O3, (iv) slurry
      amended with industrial grade liquid poly-aluminum chloride (PAC) comprising 10%
      Al2O3, and (v) slurry amended with lime. During the first rainfall event, lime
      was ineffective but alum and PAC effectively reduced dissolved reactive P (DRP)
      (by 95 and 98%, respectively) and total P (TP) flow-weighted-mean-concentrations
      (by 82 and 93%, respectively) in runoff compared to the study-control. However,
      flow-weighted-mean-concentrations of ammonium-N (NH4--N) in runoff were increased
      with alum- (81%) and lime-treated (11%) slurry compared to the study-control
      whereas PAC reduced the NH4--N by 82%. Amendments were not observed to have a
      significant effect on NO3--N losses during this study. Slurry amendments reduced
      P losses for the duration of the study, whereas the effect of amendments on N
      losses was not significant following the first event. Antecedent volumetric water
      content of the soil or slope of the plots did not appear to affect runoff volume.
      However, runoff volumes (and consequently loads of P and N) were observed to
      increase for the chemically amended plots compared to the control and soil-only
      plots. This work highlights the importance of considering both P and N losses
      when implementing a specific nutrient mitigation measure.

PMID- 23137979
TI  - Comparative effect of pesticides on brain acetylcholinesterase in tropical fish.
AB  - Monitoring of pesticides based on acetylcholinesterase (AChE; EC 3.1.1.7)
      inhibition in vitro avoids interference of detoxification defenses and
      bioactivation of some of those compounds in non-target tissues. Moreover,
      environmental temperature, age and stress are able to affect specific enzyme
      activities when performing in vivo studies. Few comparative studies have
      investigated the inter-specific differences in AChE activity in fish. Screening
      studies allow choosing the suitable species as source of AChE to detect
      pesticides in a given situation. Brain AChE from the tropical fish: pirarucu
      (Arapaima gigas), cobia (Rachycentron canadum) and Nile tilapia (Oreochromis
      niloticus) were characterized and their activities were assayed in the presence
      of pesticides (the organophosphates: dichlorvos, diazinon, chlorpyrifos,
      temephos, tetraethyl pyrophosphate- TEPP and the carbamates: carbaryl and
      carbofuran). Inhibition parameters (IC50 and Ki) for each species were found and
      compared with commercial AChE from electric eel (Electrophorus electricus).
      Optimal pH and temperature were found to be 8.0 and 35-45  degrees C,
      respectively. A. gigas AChE retained 81% of the activity after incubation at 50 
      degrees C for 30 min. The electric eel enzyme was more sensitive to the compounds
      (mainly carbofuran, IC50 of 5 nM), excepting the one from A. gigas (IC50 of 9 nM)
      under TEPP inhibition. These results show comparable sensitivity between purified
      and non-purified enzymes suggesting them as biomarkers for organophosphorus and
      carbamate detection in routine environmental and food monitoring programs for
      pesticides.

PMID- 23137980
TI  - Controlled experimental soil organic matter modification for study of organic
      pollutant interactions in soil.
AB  - Interactions of organic pollutants with soil organic matter can be studied by
      adsorption of the pollutants on well-characterized soil samples with constant
      mineralogy but different organic matter compositions. Therefore, the objectives
      of the current study are establishing a set of different, well-characterized soil
      samples by systematic modifications of their organic matter content and molecular
      composition and prove these modifications by advanced complementary analytical
      techniques. Modifications were done by off-line pyrolysis and removal/addition of
      hot-water extracted organic fraction (HWE) from/to the original soil sample. Both
      pyrolysis-field ionization mass spectrometry (Py-FIMS) and synchrotron-based C-
      and N- X-ray absorption near-edge structure spectroscopy (XANES) were applied to
      investigate the composition of the soil organic matter. These complementary
      analytical methods in addition to elemental analysis agreed in showing the
      following order of organic matter contents: pyrolyzed soil<soil residue<original
      soil<soil+3 HWE<soil+6 HWE<HWE. The addition of HWE to the soil sample increases
      the relative proportions of carbohydrates, N-containing heterocyclic compounds
      and peptides, and decreases the relative proportions of phenols, lignin monomers
      and dimers, and lipids. The most abundant organic compound classes in the
      pyrolyzed sample are aromatics, aliphatic nitriles, aldehydes, five- and six
      membered N-containing heterocyclic compounds, and aliphatic carboxylic acids. It
      can be expected that removal or addition of HWE, that mimic biomass inputs to
      soil or soil amendments, change the binding capacity for organic pollutants less
      intensively than heat impact, e.g. from vegetation burning. It will be possible
      to interpret kinetic data on the pollutants adsorption by these original and
      modified soil samples on the basis of the bond- and element-specific speciation
      data through C-XANES and N-XANES and the molecular-level characterization through
      Py-FIMS. Finally, this combination of analytical techniques can be recommended
      for similar problems that require characterizing the bulk, non-extracted SOM
      instead of pre-selected compounds or compound classes.

PMID- 23137981
TI  - Modeling of soil erosion and sediment transport in the East River Basin in
      southern China.
AB  - Soil erosion is a major global environmental problem that has caused many issues
      involving land degradation, sedimentation of waterways, ecological degradation,
      and nonpoint source pollution. Therefore, it is significant to understand the
      processes of soil erosion and sediment transport along rivers, and this can help
      identify the erosion prone areas and find potential measures to alleviate the
      environmental effects. In this study, we investigated soil erosion and identified
      the most seriously eroded areas in the East River Basin in southern China using a
      physically-based model, Soil and Water Assessment Tool (SWAT). We also introduced
      a classical sediment transport method (Zhang) into SWAT and compared it with the
      built-in Bagnold method in simulating sediment transport process along the river.
      The derived spatial soil erosion map and land use based erosion levels can
      explicitly illustrate the identification and prioritization of the critical soil
      erosion areas in this basin. Our results also indicate that erosion is quite
      sensitive to soil properties and slope. Comparison of Bagnold and Zhang methods
      shows that the latter can give an overall better performance especially in
      tracking the peak and low sediment concentrations along the river. We also found
      that the East River is mainly characterized by sediment deposition in most of the
      segments and at most times of a year. Overall, the results presented in this
      paper can provide decision support for watershed managers about where the best
      management practices (conservation measures) can be implemented effectively and
      at low cost. The methods we used in this study can also be of interest in
      sediment modeling for other basins worldwide.

PMID- 23137982
TI  - Effects of tropical montane forest disturbance on epiphytic macrolichens.
AB  - The high diversity of epiphytes typical of undisturbed montane tropical forests
      has been negatively affected by continuous deforestation and forest conversion to
      secondary vegetation. Macrolichens are an important component of these epiphytes.
      Because their physiology is strongly coupled to humidity and solar radiation, we
      hypothesized that microclimatic changes derived from forest clearing and logging
      can affect the diversity of these poikilohydric organisms. In southern Ecuador,
      we examined three types of forests according to a disturbance gradient (primary
      forests, secondary forests, and monospecific forests of Alnus acuminata) for the
      presence/absence and coverage of epiphytic macrolichens that we identified on 240
      trees. We found that total richness tended to decrease when the range of the
      disturbance increased. The impoverishment was particularly drastic for "shade
      adapted lichens", while the richness of "heliophytic lichens" increased in the
      drier conditions of secondary growth. Epiphytic composition also differed
      significantly among the three types of forests, and the similarity decreased when
      the range of the disturbance was greater. We concluded that a span of 40 years of
      recovery by secondary vegetation was not enough to regenerate the diversity of
      epiphytic macrolichens that was lost due to forest disturbances.

PMID- 23137983
TI  - Modeling sediment resuspension-induced DO variation in fine-grained streams.
AB  - Dissolved Oxygen (DO) levels in streams with nutrient enriched fine-grained
      sediment are highly affected by sediment resuspension. This paper presents a new
      model, called VART-DOS model, for simulation of instream DO transport, DO
      exchanges across water-sediment and water-air interfaces, and DO variation in
      response to sediment resuspension. The sediment resuspension effect is described
      by introducing a lumped term as a product of DO concentration and a rate of
      sediment resuspension-induced DO consumption (Lambda). The rate parameter Lambda
      is defined as a nonlinear function of average summer temperature of water and
      several sediment erosion-related parameters. This is a novel and unique feature
      of the VART-DOS model. Based on sensitivity analysis, effects of BOD and Sediment
      Oxygen Demand (SOD) on DO consumption are not so important as compared to
      sediment resuspension which can cause up to 83% reduction in DO level during high
      flow. The VART-DOS model was applied to the Lower Amite River in Louisiana, USA
      to perform continuous simulations of DO fluctuations in the winter month January
      and the summer month July involving several flood-induced sediment resuspension
      events. Simulation results indicate that the VART-DOS model is capable of
      capturing overall variation trends in DO concentration. The Normalized Root Mean
      Square Error (RMSE) between VART-DOS simulated and observed DO levels was 0. 42
      for January and 0.23 for July, demonstrating the efficacy of the VART-DOS model.

PMID- 23137984
TI  - Occurrence of brominated flame retardants in household and car dust from the
      Czech Republic.
AB  - The levels and profiles of 16 polybrominated diphenyl ethers congeners (PBDEs),
      three isomers of hexabromocyclododecane (HBCD) and other six "alternative"
      brominated flame retardants (BFRs) in dust collected in 25 Czech households and
      27 car interiors were investigated. The Sigma16 PBDEs contents varied widely with
      maximum concentrations reaching up to 5896 and 33728 MUg/kg in house and car
      dust, respectively. The highest concentrations of PBDEs were observed for BDE
      209, which was found almost in all samples and exceeded concentrations of other
      PBDEs even by one order of magnitude. The profile and levels of Penta-, Octa-,
      and DecaBDE obtained within this study were comparable to those presented in
      other studies worldwide and confirmed lower contamination of dust from Europe
      compared to North America. From the group of "alternative" BFRs, suitable for
      commercial applications as an alternative to banned PBDEs, mainly
      decabromodiphenyl ethane (DBDPE) and HBCD were detected in the concentration
      ranges <20-3567 and <0.3-950 MUg/kg, respectively. gamma-HBCD was dominating,
      forming up to 70% of SigmaHBCD. Using the measured concentrations and estimates
      of dust ingestion rates it was estimated that toddlers had a higher exposure than
      adults for all compounds investigated.

PMID- 23137985
TI  - Seasonal variation of the 137Cs level and its relationship with potassium and
      carbon levels in conifer needles.
AB  - Seasonal variations in foliar 137Cs levels were examined in Norway spruce (Picea
      abies (L.) Karst.), and Scots pine (Pinus sylvestris L.) in western Finland. Our
      aim was to test the occurrence of seasonal variation in contents and
      concentrations of 137Cs, potassium and carbon in needles. The study focused on
      analysing levels of total 137Cs in the three youngest needle age classes and
      comparing them to the levels of potassium and carbon. Spruce and pine needles
      were collected from 50- and 65-year-old stands on 18 sampling occasions between
      April 1996 and February 1997. Phases of intensive growth, needle elongation and
      dormancy were apparent in the time series for the needle contents and activity
      concentration of 137Cs, both of which varied according to needle age class and
      tree species. The sequence of phases with a temporal fluctuation of needle
      contents, activity concentrations of 137Cs and concentrations of K and carbon
      varied occasionally, and the efficiency of their translocation revealed some
      differences in the dynamics of 137Cs, K and carbon in spruce and pine. The data
      clearly showed that the needles' K contents responded strongly to changes in K
      demand from other parts of the tree due to seasonal changes and that these
      responses were stronger than the associated retranslocations of 137Cs,
      particularly in Scots pine. During intensive growth, K was less mobile than 137Cs
      in the needles. The uptake of 137Cs by current-year needles is simultaneously
      affected by uptake from the soil via the roots and retranslocation from other
      internal sources, and both of these processes affect the observed transfer rates
      during the growth period. Our results provided information on the transfer rates
      and revealed differentiation of root uptake and retranslocation of 137Cs in
      needles. The study can support dynamic modelling of atmospheric 137Cs
      contamination in forests.

PMID- 23137986
TI  - Ant cuticles: a trap for atmospheric phthalate contaminants.
AB  - Phthalates are universal contaminants. We show that they are trapped by the ant
      cuticles and maintained permanently at a low level, generally less than 1% of
      cuticular components. They are found throughout the interior of the insect,
      predominately in the fat body, which suggests that they are adsorbed by the
      cuticle. In open plastic boxes free of phthalates the ants became more
      contaminated with phthalates over a period of time, whereas in closed glass jars
      they did not. This finding suggests that the main source of pollutants is the
      atmosphere. Different ant species collected from multiple places showed similar
      levels of contamination. It appeared that in some pristine places the
      contamination was lower, but this needs to be confirmed. Ants can be considered
      as bio-indicators of phthalate pollution.

PMID- 23137987
TI  - Risk assessment of episodic exposures to chemicals should consider both the
      physiological and the ecological sensitivities of species.
AB  - In flowing water pollution regularly occurs in short pulses (hours to days).
      Populations of species affected by pulses have the potential to recover in the
      absence of further disturbance but recovery rates will vary between species due
      to resilience (e.g. generation time and dispersal ability) and avoidance traits.
      Current assessments of the risks of chemicals to community structure-
      predominantly based on species sensitivity distributions (SSDs)--only consider
      physiological sensitivity and do not give any consideration as to the rate at
      which populations will recover. We constructed SSDs of ecologically sensitive and
      tolerant stream invertebrate assemblages (based on 3 traits previously shown to
      be important in determining how species relative abundances respond to pesticide
      toxicity) from south-east Australia and in regions of Finland, Germany and
      France. There were differences in SSDs of a generic measure of physiological
      sensitivity to organic chemicals between ecologically sensitive and tolerant
      species, though these differences were not consistent between the regions
      studied. We conclude that it is important for community level risk assessments of
      pulses of chemicals that the ecological sensitivity of the regional species
      assemblage is considered and discuss several options as to how this could be
      achieved.

PMID- 23137988
TI  - Global versus local change effects on a large European river.
AB  - Water temperature and discharge are fundamental to lotic ecosystem function, and
      both are strongly affected by climate. In large river catchments, however,
      climatic effects might be difficult to discern from background variability and
      other cumulative sources of anthropogenic change arising from local land and
      water management. Here, we use trend analysis and generalised linear modelling on
      the Loire, the longest river in France to test the hypotheses that i) long-term
      trends in discharge and river temperature have arisen from climate change and ii)
      climatic effects on water quality have not been overridden by local effects. Over
      32 years (1977-2008), discharge in the Middle Loire fell by about 100 m3/s while
      water temperature increased by 1.2  degrees C with greatest effects during the
      warm period (May-August). Although increasing air temperature explained 80% of
      variations in water temperature, basin-wide precipitation showed no long-term
      trend and accounted for only 18% of inter-annual fluctuations in flow. We suggest
      that trends in abstraction coupled with a potential increase in evapo
      transpiration at the catchment scale could be responsible for the majority of the
      long-term discharge trend. Discharge and water temperature explained only 20% of
      long-term variations in major water quality variables (conductivity, dissolved
      oxygen, pH, suspended matter, biochemical oxygen demand, nitrate, phosphate and
      chlorophyll-a), with phosphate and chlorophyll declining contrary to expectations
      from global change probably as a consequence of improved wastewater treatment.
      These data partially support our first hypothesis in revealing how warming in the
      Loire has been consistent with recent atmospheric warming. However, local
      management has had larger effects on discharge and water quality in ways that
      could respectively exacerbate (abstraction) or ameliorate (reduced point-source
      pollution) warming effects. As one of the first case-studies of its kind, this
      multi-parametric study illustrates the potential for complex interactions between
      climate change and other environmental factors in large rivers.

PMID- 23137989
TI  - Molecular docking, molecular dynamics simulation, and structure-based 3D-QSAR
      studies on estrogenic activity of hydroxylated polychlorinated biphenyls.
AB  - Hydroxylated polychlorinated biphenyls (HO-PCBs), major metabolites of PCBs, have
      been reported to present agonist or antagonist interactions with estrogen
      receptor alpha (ERalpha) and induce ER-mediated responses. In this work, a
      multistep framework combining molecular docking, molecular dynamics (MD)
      simulations, and structure-based three-dimensional quantitative structure
      activity relationship (3D-QSAR) studies were performed to explore the influence
      of structural features on the estrogenic activities of HO-PCBs, and to
      investigate the molecular mechanism of ERalpha-ligand interactions. The CoMSIA
      (comparative molecular similarity indices analysis) model was developed from the
      conformations obtained from molecular docking. The model exhibited statistically
      significant results as the cross-validated correlation coefficient q2 was 0.648,
      the non-cross-validated correlation coefficient r2 was 0.968, and the external
      predictive correlation coefficient r(pred)2 was 0.625. The key amino acid
      residues were identified by molecular docking, and the detailed binding modes of
      the compounds with different activities were determined by MD simulations. The
      binding free energies correlated well with the experimental activity. An
      energetic analysis, MM-GBSA energy decomposition, revealed that the van der Waals
      interaction was the major driving force for the binding of compounds to ERalpha.
      The hydrogen bond interactions between the ligands and residue His524 help to
      stabilize the conformation of ligands at the binding pocket. These results are
      expected to be beneficial to predict estrogenic activities of other HO-PCB
      congeners and helpful for understanding the binding mechanism of HO-PCBs and
      ERalpha.

PMID- 23137990
TI  - Assessment of diffuse contamination of agricultural soil by copper in Aquitaine
      region by using French national databases.
AB  - A long-term application of copper-based fungicides to fight against downy mildew
      has led to soil contamination by copper particularly in Aquitaine region where
      viticulture is important. This work aims to statistically validate the origin of
      diffuse contamination of Aquitaine agricultural soils and show that contamination
      is closely related to wine-growing in this region. For this purpose, several
      national databases have been used. From the French National Soil Monitoring
      Network (Reseau de Mesures de la Qualite des sols RMQS) data, an Exploratory Data
      Analysis (EDA) was performed to bring out the copper contamination. The French
      test soil database (Base de Donnees des Analyses de Terre BDAT) and the national
      census of agriculture (Recensement General Agricole RGA) have been crossed. A
      statistical approach has been used to determine the relationship between the
      median concentration of copper extracted by Ethylene Diamine Tetra-acetic Acid
      (EDTA) referred to as CuEDTA in cultivated topsoils of the Aquitaine region and
      the ratio between winegrowing area (Svine) and the Used Agricultural Area (UAA)
      expressed as the form Svine/UAA. The results revealed a strongly significant
      exponential correlation between these two variables. They allow concluding that
      at cantonal scale, when vines cover more than 80% of the UAA, an overexposure of
      soils to the diffuse contamination by copper can occur.

PMID- 23137991
TI  - Short and user-friendly: The development and validation of the Mini-DBQ.
AB  - The Driver Behavior Questionnaire (DBQ) is used to measure aberrant driver
      behavior by asking drivers how often they engage in various aberrant driver
      behaviors. Since the development of the original DBQ, several modified versions
      have been developed. The difference between the various versions is that new
      items are added or existing items modified or excluded. However, despite the
      differences, all versions are relatively long and therefore time-consuming and
      tiring to answer, which might limit the usability of the instrument. The main
      purpose of the present study was to develop a mini DBQ version by reducing the 27
      item original DBQ to the shortest possible DBQ version. A second aim was to
      explore the feasibility of a second-order structure within the data, which means
      that violations, errors and lapses factors load on a higher-order aberrant driver
      behavior factor. The presence of a second-order structure further indicates the
      validity of the DBQ and its theoretical structure. Confirmatory factor analysis
      (CFA) was used to test the fit (i.e., how well the models explain the data) of
      the original DBQ versus the fit of the shortest possible DBQ, as well as the
      presence of a second-order structure for the DBQ. The results indicated a nine
      item Mini-DBQ. In addition, a second-order structure was established in the data.
      These findings indicate that the Mini-DBQ is a valid and useful short measure of
      aberrant driver behavior.

PMID- 23137993
TI  - Resonant, non-resonant and anomalous states of Dirac electrons in a parabolic
      well in the presence of magnetic fields.
AB  - We report on several new basic properties of a parabolic dot in the presence of a
      magnetic field. The ratio between the potential strength and the Landau level
      (LL) energy spacing serves as the coupling constant of this problem. In the weak
      coupling limit the energy spectrum in each Hilbert subspace of an angular
      momentum consists of discrete LLs of graphene. In the intermediate coupling
      regime non-resonant states form a closely spaced energy spectrum. We find,
      counter-intuitively, that resonant quasi-bound states of both positive and
      negative energies exist in the spectrum. The presence of resonant quasi-bound
      states of negative energies is a unique property of massless Dirac fermions. As
      the strong coupling limit is approached resonant and non-resonant states
      transform into anomalous states, whose probability densities develop a narrow
      peak inside the well and another broad peak under the potential barrier. These
      properties may investigated experimentally by measuring optical transition
      energies that can be described by a scaling function of the coupling constant.

PMID- 23137992
TI  - Effect of long-term and short-term dynamic mechanical evaluation of networks
      based on urethane and soybean oil.
AB  - The intermixing between urethane acrylate (UA) prepolymer and acrylated
      epoxidized soybean oil (AESO) by thermal polymerization results in a product with
      promising properties for biomedical application. The results of dynamic
      mechanical analysis (DMA) performed on the polymerized UA, in a limited range of
      frequencies (0.5-10 Hz), have raised questions related to the origin of
      relaxations. Whether a molecular motion can be associated with a relaxation
      process was ascertained by performing experiments in a much larger frequency
      range, in a step-scan DMA experiment. The particularities of this experiment made
      possible to evidence unequivocally the alpha-relaxations for the urethane
      domains, organized in a hydrogen bond physical network, and to register the
      transformations associated with the breaking of hydrogen bonds. Incorporation of
      AESO has gradually loosened the physical network and transformed it into a mixed
      urethane-AESO chemical network. The properties of urethane-AESO networks are
      ruled by the double function of AESO: plasticizer and crosslinker. The evolution
      of secondary relaxations reflected also the changes that occur in the urethane
      AESO samples. During the step-scan procedure supplementary changes were induced
      in the samples with high AESO content, at high temperature. The morphology of the
      networks was investigated by electronic microscopy studies.

PMID- 23137994
TI  - Glans amputation during routine neonatal circumcision: mechanism of injury and
      strategy for prevention.
AB  - OBJECTIVE: Glans injury during circumcision is an uncommon yet potentially
      devastating complication. Its mechanism remains poorly understood. Herein we
      critically evaluate a case series and, based on common characteristics,
      hypothesize the mechanism of injury as well as means to prevent it. METHODS:
      Retrospective review of circumcision-related glans amputation cases referred for
      evaluation and management, focusing on detection of common history and
      presentation patterns in order to evaluate possible underlying mechanisms.
      RESULTS: A neonatal elective circumcision was conducted using a Mogen clamp and
      an oblique injury to the ventro-lateral aspect of the glans was noted in 6 cases
      referred over a 5-year period, suggesting a similar trauma pattern. The urethra
      was consistently involved. The amputated segments were reattached as free
      composite grafts in 2/6 cases. Three patients underwent delayed glansplasty
      months after the trauma in an attempt to restore natural symmetry and cosmesis.
      In one case a buccal mucosa graft was employed to rebuild the ventral coronal
      sulcus. CONCLUSIONS: Trauma pattern suggests that the ventral glans is at high
      risk for injury by traction on incompletely released ventral preputial adhesions
      with subsequent glans entrapment. Practitioners performing neonatal
      circumcisions, particularly with a Mogen clamp, should exercise adequate release
      of ventral adhesions to prevent this complication.

PMID- 23137995
TI  - Durable bonding to mechanically and/or chemically pre-treated dental zirconia.
AB  - OBJECTIVES: To evaluate the effect of mechanical and chemical surface pre
      treatment on the bond durability of two composite cements to dental zirconia.
      METHODS: Fully sintered IPS e.max ZirCAD (Ivoclar-Vivadent) blocks were either
      subjected to tribochemical silica sandblasting (CoJet, 3M ESPE) or not
      mechanically pre-treated. Next, the zirconia samples were either additionally pre
      treated using one of two silane/MDP-combined ceramic primers (Clearfil Ceramic
      Primer, Kuraray; Monobond Plus, Ivoclar-Vivadent), or not further chemically pre
      treated. Finally, two identically pre-treated zirconia blocks were bonded
      together using either a conventional BisGMA-based (Clearfil Esthetic Cement,
      Kuraray) or an MDP-based (Panavia F2.0, Kuraray) 'self-etch' dual-cure composite
      cement. The specimens were trimmed at the interface to a cylindrical hour-glass
      shape and stored for 7 days in distilled water (37 degrees C), after which they
      were randomly exposed to one of three ageing protocols: (1) immersed in 37
      degrees C water for 10 days (10d); (2) subjected to 10,000 thermo-cycles (TC); or
      (3) immersed in 37 degrees C water for 6 months (6m). After storage, the micro
      tensile bond strength (MUTBS) was determined in MPa (n=15-21/group).
      Fractographic analysis was performed using SEM. RESULTS: Weibull analysis
      revealed the highest Weibull scale and shape parameters for the 'CoJet/Clearfil
      Ceramic Primer/Panavia F2.0/10d' combination. While the BisGMA-based composite
      cement Clearfil Esthetic Cement (Kuraray) bonded equally well to zirconia using
      either tribochemical silica sandblasting (CoJet, 3M ESPE) or not, sandblasting
      appeared indispensable for the MDP-based and more hydrophilic composite cement
      Panavia F2.0 (Kuraray). CONCLUSIONS: Combined mechanical and chemical pre
      treatment can best be recommended to durably bond to zirconia. CLINICAL
      SIGNIFICANCE: As a standard procedure to durable bond zirconia to tooth tissue,
      both mechanical (tribochemical silica coating) and chemical (silane/MDP-combined
      ceramic primers) is clinically highly recommended.

PMID- 23137996
TI  - An in vitro investigation of the effect of bevel design on the penetration and
      withdrawal forces of dental needles.
AB  - OBJECTIVES: To compare the effect on insertion and withdrawal forces using
      needles with a standard atraumatic bevel to those with a novel asymmetrical bevel
      in vitro. METHODS: Maximum needle penetration forces were measured using a 10N
      load cell mounted on an Instron universal testing machine. Forces were determined
      during insertion through a 0.4mm polyurethane membrane mounted at 90 degrees 
      (n=30 of each design), 30 degrees  (n=16 of each design) and 150 degrees  (n=16
      of each design) to the needle bevel and during a 10mm insertion into a polyvinyl
      siloxane block mounted at 90 degrees  to the bevel (n=16 of each design). In all
      tests the rate of insertion was 50mm/min. RESULTS: The novel design required less
      force to penetrate the membrane at 30 degrees  and 150 degrees  compared to the
      standard design (mean forces at 30 degrees  being 0.75N and 0.98N for novel and
      standard designs respectively [p<0.001] and at 150 degrees  0.52N and 0.66N
      respectively [p<0.001] but more force at 90 degrees  penetration tests (0.60N and
      0.46N respectively [p<0.001]). The novel design required less force to insert
      10mm into the polyvinyl siloxane (1.80N and 2.54N respectively [p<0.001]).
      CONCLUSION: The novel design needed less force than the standard version to
      penetrate a thin membrane when used at 30 degrees  and 150 degrees  to the
      surface and to penetrate a polyvinyl siloxane block to a depth of 10mm but
      required more force to penetrate a thin membrane at 90 degrees . CLINICAL
      SIGNIFICANCE: Needle bevel design affects the penetration and withdrawal forces
      of dental needles in vitro.

PMID- 23137997
TI  - Assessment of a new scoring system for predicting non-sentinel node positivity in
      sentinel node-positive melanoma patients.
AB  - BACKGROUND: When completion lymph node dissection (CLND) is performed in sentinel
      node (SN)-positive melanoma patients, a positive non-sentinel node (NSN) is found
      in approximately 20% of them. Recently, Murali et al. proposed a new scoring
      system (non-sentinel node risk score, N-SNORE) to predict the risk of NSN
      positivity in SN-positive patients. The objectives of the current study were to
      identify factors predicting NSN positivity and to assess the validity of the N
      SNORE in an independent patient cohort. METHODS: All SN-positive patients who
      underwent CLND at a single institution between 1995 and 2010 were analyzed.
      Characteristics of the patient, primary melanoma, and SN(s) were tested for
      association with NSN positivity. Missing values were reconstructed using multiple
      imputation to enable multivariable analysis. RESULTS: CLND revealed positive NSNs
      in 30 (23%) of 130 SN-positive patients. Primary melanoma regression (p = 0.03)
      was independently associated with NSN positivity. After adjustment because of
      missing data on perinodal lymphatic invasion, N-SNORE proved to be a significant
      stratification model in our patient cohort (p = 0.003): 5.9% NSN positivity in
      the very low risk category and 75.0% NSN positivity in the very high risk
      category. CONCLUSIONS: Presence of regression in the primary melanoma was
      independently associated with a higher risk of NSN positivity. The slightly
      modified N-SNORE scoring system provided useful stratification of the risk for
      NSN positivity. However, lack of perinodal lymphatic invasion data may have
      reduced its predictive value.

PMID- 23137999
TI  - The role of BDNF, NTRK2 gene and their interaction in development of treatment
      resistant depression: data from multicenter, prospective, longitudinal clinic
      practice.
AB  - BACKGROUND: Although genetic variants may play a key role in development of
      treatment-resistant depression (TRD), relevant research is scarce. METHODS: To
      examine whether the polymorphisms of BDNF (rs6265) and NTRK2 (rs1387923,
      rs2769605 and rs1565445) genes confer risk for TRD in major depressive disorder
      (MDD), a total of 948 MDD patients were recruited in a 12-week, multicenter,
      prospective longitudinal study. RESULTS: Our study showed a significant allelic
      association between rs1565445 and TRD with an excess of the T allele in the TRD
      group, compared to non-TRD group (OR = 1.43, 95%CI: 1.16-1.76, p = 0.0008); while
      patients with genotype C/C and T/C in rs1565445 were less likely to develop TRD
      than those carrying T/T (OR = 0.52, 95%CI: 0.33-0.82; OR = 0.72, 95%CI: 0.54
      0.97, respectively; p = 0.005). Haplotype T-T (rs1565445 and rs1387923) had 1.41
      fold increased risk of TRD (p = 0.0014). Furthermore, significant four-locus
      (rs1387923-rs1565445-rs2769605-rs6265) gene-gene interactions were detected by
      the Multifactor-dimensionality reduction (MDR) method. DISCUSSION: These results
      suggest that the interactions of BDNF (rs6265) with NTRK2 (rs1387923, rs2769605
      and rs1565445) gene polymorphisms likely play an essential role in the
      development of TRD in Han Chinese MDD patients.

PMID- 23138000
TI  - The hazards of cross comparing the drug toxicity results from different trials in
      metastatic renal cancer: in response to a letter from Dr. Catala-Lopez.

PMID- 23138001
TI  - Probing biofouling resistant polymer brush surfaces by atomic force microscopy
      based force spectroscopy.
AB  - The protein repellency and biofouling resistance of zwitterionic
      poly(sulfobetaine methacrylate)(pSBMA) brushes grafted via surface initiated
      polymerization (SIP) from silicon and glass substrata was assessed using atomic
      force microscopy (AFM) adherence experiments. Laboratory settlement assays were
      conducted with cypris larvae of the barnacle Balanus amphitrite. AFM adherence
      includes the determination of contact rupture forces when AFM probe tips are
      withdrawn from the substratum. When the surface of the AFM tip is modified,
      adherence can be assessed with chemical specifity using a method known as
      chemical force microscopy (CFM). In this study, AFM tips were chemically
      functionalized with (a) fibronectin- here used as model for a nonspecifically
      adhering protein - and (b) arginine-glycine-aspartic acid (RGD) peptide motifs
      covalently attached to poly(methacrylic acid) (PMAA) brushes as biomimics of
      cellular adhesion receptors. Fibronectin functionalized tips showed significantly
      reduced nonspecific adhesion to pSBMA-modified substrata compared to bare gold
      (2.3+/-0.75 nN) and octadecanethiol (ODT) self-assembled monolayers (1.3+/-0.75
      nN). PMAA and PMAA-RGD modified probes showed no significant adhesion to pSBMA
      modified silicon substrata. The results gathered through AFM protein adherence
      studies were complemented by laboratory fouling studies, which showed no adhesion
      of cypris larvae of Balanus amphitrite on pSBMA. With regard to its unusually
      high non-specific adsorption to a wide variety of materials the behavior of
      fibronectin is analogous to the barnacle cyprid temporary adhesive that also
      binds well to surfaces differing in polarity, charge and free energy. The
      antifouling efficacy of pSBMA may, therefore, be directly related to the ability
      of this surface to resist nonspecific protein adsorption.

PMID- 23138002
TI  - Study on the P-wave feature time course as early predictors of paroxysmal atrial
      fibrillation.
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical
      practice, increasing the risk of stroke and all-cause mortality. Its mechanisms
      are poorly understood, thus leading to different theories and controversial
      interpretation of its behavior. In this respect, it is unknown why AF is self
      terminating in certain individuals, which is called paroxysmal AF (PAF), and not
      in others. Within the context of biomedical signal analysis, predicting the onset
      of PAF with a reasonable advance has been a clinical challenge in recent years.
      By predicting arrhythmia onset, the loss of normal sinus rhythm could be
      addressed by means of preventive treatments, thus minimizing risks for the
      patients and improving their quality of life. Traditionally, the study of PAF
      onset has been undertaken through a variety of features characterizing P-wave
      spatial diversity from the standard 12-lead electrocardiogram (ECG) or from
      signal-averaged ECGs. However, the variability of features from the P-wave time
      course before PAF onset has not been exploited yet. This work introduces a new
      alternative to assess time diversity of the P-wave features from single-lead ECG
      recordings. Furthermore, the method is able to assess the risk of arrhythmia 1 h
      before its onset, which is a relevant advance in order to provide clinically
      useful PAF risk predictors. Results were in agreement with the
      electrophysiological changes taking place in the atria. Hence, P-wave features
      presented an increasing variability as PAF onset approximates, thus suggesting
      intermittently disturbed conduction in the atrial tissue. In addition, high PAF
      risk prediction accuracy, greater than 90%, has been reached in the two
      considered scenarios, i.e. discrimination between healthy individuals and PAF
      patients and between patients far from PAF and close to PAF onset. Nonetheless,
      more long-term studies have to be analyzed and validated in future works.

PMID- 23138003
TI  - Poxvirus antagonism of innate immunity by Bcl-2 fold proteins.
AB  - Poxviruses have evolved numerous mechanisms to evade host innate immunity.
      Sensory pathways that are activated by Toll-like and nucleotide receptors, as
      well as innate cell death pathways, are both targets of antagonism by viral
      proteins. Recent structural, biochemical and functional studies of poxvirus
      proteins have identified a family of alpha-helical proteins that adopt a Bcl-2
      fold despite highly divergent polypeptide sequences from cellular proteins that
      regulate apoptosis. These newly identified proteins have assumed new roles in
      antagonism of NF-kappaB and interferon signaling pathways and interfere with the
      release of pro-inflammatory cytokines. Structures of isolated viral proteins and
      their complexes with cellular targets provide insight into the diverse ways that
      the Bcl-2 scaffold can be exploited for antagonism of host immunity.

PMID- 23138005
TI  - Serum gamma-glutamyltransferase as a risk factor for general cardiovascular
      disease prediction in Koreans.
AB  - OBJECTIVE: Gamma-glutamyltransferase (GGT) is a novel cardiovascular disease
      (CVD) risk factor, but its use as an independent factor for general CVD risk
      prediction remains unclear in general population. This study examined the
      association between serum GGT concentration and 10-year CVD risk in Koreans.
      METHODS: This cross-sectional study was performed on 27,270 Koreans. Besides
      individual components of 10-year CVD risk, body mass index, fasting blood
      glucose, liver enzymes, lipid profile, uric acid and high sensitive C-reactive
      protein data were used. The study subjects were grouped into quartiles according
      to the levels of GGT. Analyses relating GGT to 10-year CVD risk greater than 20%
      used multiple confounders-adjusted logistic regression. RESULTS: Positive
      correlations were established between log-transformed GGT concentration and 10
      year CVD risk (Spearman's rho = 0.51; P < 0.001). Compared to the lowest baseline
      GGT category, unadjusted odds ratios for 10-year CVD risk greater than 20% were
      significantly increased from the lowest to the highest GGT quartiles; these
      results remained significant after adjustments for multiple confounders.
      CONCLUSION: Increased GGT concentration is associated with the increase in 10
      year CVD risk. Serum GGT may be helpful to predict the future risk of general
      CVD.

PMID- 23138004
TI  - Characterization of beta-domains in C-terminal fragments of TDP-43 by scanning
      tunneling microscopy.
AB  - The TAR DNA-binding protein 43 (TDP-43) has been identified as a critical player
      in a range of neurodegenerative diseases, including frontotemporal lobar
      degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Recent discoveries
      demonstrate the important role of carboxyl-terminal fragments of TDP-43 in its
      proteinopathy. Herein, we report the characterization of beta-domains in the C
      terminal fragments of TDP-43 using scanning tunneling microscopy (STM). Careful
      comparison of the wild-type TDP-43 (Wt) and the three mutant TDP-43 peptides: an
      ALS-related mutant peptide: phosphorylated A315T mutant TDP-43 (A315T(p)) and two
      model peptides: A315T mutant TDP-43 (A315T), A315E mutant TDP-43 (A315E) reveals
      that A315T(p) has a longer core region of the beta-domain than Wt. A315E
      possesses the longest core region of the beta-domain and A315T(p) mutant TDP-43
      has the second longest core region of the beta-domain. The core regions of the
      beta-domains for A315T and Wt TDP-43 have the same length. This observation
      provides a supportive evidence of a higher tendency in beta-sheet formation of
      A315T(p) containing TDP-43 fragment, and structural mechanism for the higher
      cytotoxicity and accelerated fibril formation of the A315T(p) mutation-containing
      TDP-43 peptide as compared with Wt TDP-43.

PMID- 23138006
TI  - High-protein diets alters body composition and improves insulin resistance in a
      rat model of low birth weight.
AB  - OBJECTIVE: We aimed to investigate the effects of early high-protein
      supplementation on low birth weight (LBW)-associated adult metabolic
      disturbances. MATERIALS AND METHODS: This study involved 32 LBW rat pups that
      were fed a normal protein (20% of energy intake) diet or high-protein (30% of
      energy intake) diet on their first 4 weeks of life. Sixteen rat pups with normal
      birth weight (NBW) fed the normal-protein diet were included as control.
      Biochemical measurements were performed at 4 and 12 weeks of age. RESULTS: Low
      birth weight offspring showed significantly (P < 0.05) increased fat mass
      percentage and adipocyte size and decreased lean mass percentage and muscle fiber
      size relative to NBW offspring. These LBW-related changes in body composition
      were corrected by high-protein diet intervention. At 12 weeks of age, the fasting
      insulin level (7.14 +/- 0.83 vs 9.27 +/- 0.67 mU/L) and homeostasis model of
      insulin resistance (1.71 +/- 0.35 vs 2.30 +/- 0.44) were significantly lower in
      high protein-fed LBW offspring than in normal protein-fed LBW offspring. Low
      birth weight rat pups showed a significant (P < 0.05) reduction in serum
      adiponectin concentrations, glucose transporter 4 mRNA abundance, and
      phosphorylation levels of AMP-activated protein kinase (AMPK) and mammalian
      target of rapamycin (mTOR) relative to NBW controls. These LBW-associated
      alterations in gene expression were reversed by early high-protein treatment.
      CONCLUSIONS: Early postnatal high-protein intake alters the body composition and
      improves insulin resistance in adults with LBW, which is associated with
      activation of the AMPK and mTOR pathways.

PMID- 23138007
TI  - The rs9939609 gene variant in FTO modified the metabolic response of weight loss
      after a 3-month intervention with a hypocaloric diet.
AB  - BACKGROUND: Common polymorphisms in the fat mass and obesity associated gene
      (FTO) have been linked to obesity in some populations. Nevertheless, the role of
      FTO variants on body weight response after dietary intervention remains
      equivocal. OBJECTIVE: We decided to analyze the effects of the rs9939609 FTO gene
      polymorphism on body weight changes and metabolic parameters after 3 months of a
      hypocaloric diet. DESIGN: Before and after 3 months on a low-fat hypocaloric
      diet, a white population of 106 subjects with obesity was analyzed. RESULTS: Of
      the study subjects, 35 (33%) had the genotype TT and 71 (67%) had the next
      genotypes; TA (46 study subjects, 43.4%) or AA (25 study subjects, 23.6%). After
      dietary treatment and in TT group, weight, waist circumference, total
      cholesterol, LDL-cholesterol, insulin, and homeostasis model assessment decreases
      were less than subjects carrying the A allele [-3.1 (3.6) vs -2.4 (4.1) kg: P <
      0.05], waist circumference [-5.4 (6.4) vs -2.6 (4.8) cm; P < 0.05], total
      cholesterol [-12.3 (35.3) vs -6.4 (4.7) mg/dL; P < 0.05], LDL-cholesterol [-22.3
      (30.5) vs -10.7 (30.5) mg/dL; P < 0.05], insulin [-1.89 (5.5) vs +0.94 (8.2)
      mUI/L; P < 0.05], and homeostasis model assessment [-0.46 (1.11) vs -0.01 (2.4);
      P < 0.05]. CONCLUSIONS: Our study confirmed a higher weight loss in A carriers of
      FTO rs9939609 polymorphism than in TT genotype study subjects.

PMID- 23138009
TI  - A novel mass spectrometry-based assay for the accurate measurement of
      thyroglobulin from patient samples containing antithyroglobulin autoantibodies.
AB  - Thyroid cancer is the most common endocrine cancer in the United States. The
      primary treatment of thyroid cancer is partial or complete thyroidectomy in
      patients in whom the cancer is discovered preoperatively, and is often followed
      by radioactive iodine ablation. After the initial therapy, patients are followed
      up regularly, most commonly by measurement of serum thyroglobulin (Tg) levels and
      high-resolution neck ultrasound. As Tg is only produced within the thyroid gland,
      it has long been recognized as an excellent biomarker for the presence of
      residual disease after treatment. A number of immunoassays are in common use to
      measure serum Tg levels. Unfortunately, irrespective of which method is chosen,
      there is a major potential artifact, in that the presence of autoantibodies
      binding to Tg (ATG) may bias the results to the point where they are clinically
      unreliable. This article describes a liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) method for the measurement of serum Tg after tryptic
      digestion of serum samples. The method is compared to Tg analyses using both a
      Food and Drug Administration-approved immunometric assay (IMA) and a well
      respected, clinically used radioimmunoassay. In the absence of ATG, the new LC
      MS/MS assay demonstrates equivalency compared to the IMA. However, in ATG
      positive patients, the IMA Tg results are lower than the LC-MS/MS assay and the
      radioimmunoassay Tg results are typically higher. These studies demonstrate the
      accuracy and validity of the measurement of Tg by LC-MS/MS. This assay will
      permit the accurate determination of Tg levels even in patients with ATG.

PMID- 23138010
TI  - One-carbon metabolism, spermatogenesis, and male infertility.
AB  - Balanced diet is the natural source of micronutrients, such as folate and
      vitamins, vital for proper functioning of the body. One-carbon metabolic pathway
      along with folate and other vitamins plays an important role in DNA synthesis and
      in the establishment of epigenetic modifications like DNA/histone methylation.
      Spermatogenesis involves distinct cellular, genetic, and chromatin changes during
      the course of production of male gamete sperm. Folate and normal activity of 1
      carbon metabolic pathway enzymes are central to nucleotide synthesis,
      methylation, and maintenance of genomic integrity as well as protection from DNA
      damage. As a result, polymorphisms in 1-carbon metabolic pathway genes affecting
      several physiological processes also have an impact on spermatogenesis and may
      affect directly or indirectly quality of sperm. Alterations in these processes
      may be a consequence of additive effect resulting from altered expression of 1
      carbon metabolic pathway genes and/or inadequate folate/micronutrients
      supplementation. The present review provides an overview of different cellular
      and molecular events regulated by 1-carbon metabolic pathway enzymes and their
      impact on male reproductive health. It also summarizes the different studies
      where polymorphisms in the enzymes of 1-carbon metabolic pathway or folate
      deficiency are associated with male infertility and future prospects.

PMID- 23138011
TI  - Rates and causes of death from non-ST elevation acute coronary syndromes: ten
      year follow-up of the PRAIS-UK registry.
AB  - BACKGROUND: Long term nationally representative mortality rates following acute
      coronary syndrome (ACS) admissions are lacking beyond 5 years. We report rates
      and causes of mortality at approximately 10 years from PRAIS-UK. METHODS: PRAIS
      UK was a prospective registry of 1046 non-ST-elevation ACS admissions to 56 UK
      hospitals between 1998 and 1999. 493 patients surviving to 6 months were
      consented to long term follow-up. We identified deaths and causes (ICD codes) via
      the UK central death register and examined the influence of baseline
      characteristics and early revascularisation procedures. A modified GRACE risk
      score was constructed to determine the association of baseline score with long
      term risk of death. RESULTS: The mean age was 66 years and 40% were women. After
      a median follow-up of 11.6 years (IQR 6.3-11.9), 46% (225) of patients had died
      with 55% being classified as cardiovascular. In a multivariate analysis, the
      following variables were associated with higher mortality (hazard ratio [HR] and
      95% confidence intervals [CI]): age (10 years increase) 2.14 (1.87 to 2.45), ST
      depression or bundle branch block (compared to normal ECG) 1.68 (1.06 to 2.67),
      and history of heart failure (compared to no HF) 1.81 (1.28 to 2.56). The HR for
      risk of death in patients who received a revascularisation procedure (versus
      those who did not) in the first 6 months was 0.41 (0.24 to 0.69). The mean
      adapted GRACE score was 99.3 +/- 26.4, associated with approximately 50%
      mortality at 10 years. CONCLUSIONS: Non-ST elevation ACS is associated with about
      50% mortality over 10 years that may be improved by early revascularisation. Well
      designed long-term registries can provide key data to determine prognosis and
      burden of disease.

PMID- 23138012
TI  - Reply to the Hong-Lin Chen article on CONSORT (2010) recommendations.

PMID- 23138008
TI  - Physiology and pathophysiology of the blood-brain barrier: P-glycoprotein and
      occludin trafficking as therapeutic targets to optimize central nervous system
      drug delivery.
AB  - The blood-brain barrier (BBB) is a physical and metabolic barrier that separates
      the central nervous system from the peripheral circulation. Central nervous
      system drug delivery across the BBB is challenging, primarily because of the
      physical restriction of paracellular diffusion between the endothelial cells that
      comprise the microvessels of the BBB and the activity of efflux transporters that
      quickly expel back into the capillary lumen a wide variety of xenobiotics.
      Therapeutic manipulation of protein trafficking is emerging as a novel means of
      modulating protein function, and in this minireview, the targeting of the
      trafficking of 2 key BBB proteins, P-glycoprotein and occludin, is presented as a
      novel, reversible means of optimizing central nervous system drug delivery.

PMID- 23138013
TI  - Comparison of Sprint Fidelis and Riata defibrillator lead failure rates.
AB  - BACKGROUND/OBJECTIVES: Sprint Fidelis and Riata defibrillator leads are prone to
      early failure. Few data exist on the comparative failure rates and mortality
      related to lead failure. The aims of this study were to determine the failure
      rate of Sprint Fidelis and Riata leads, and to compare failure rates and
      mortality rates in both groups. METHODS: Patients implanted with Sprint Fidelis
      leads and Riata leads at a single centre were identified and in July 2012,
      records were reviewed to ascertain lead failures, deaths, and relationship to
      device/lead problems. RESULTS: 113 patients had Sprint Fidelis leads implanted
      between June 2005 and September 2007; Riata leads were implanted in 106 patients
      between January 2003 and February 2008. During 53.0 +/- 22.3 months of follow-up
      there were 13 Sprint Fidelis lead failures (11.5%, 2.60% per year) and 25 deaths.
      Mean time to failure was 45.1 +/- 15.5 months. In the Riata lead cohort there
      were 32 deaths, and 13 lead failures (11.3%, 2.71% per year) over 54.8 +/- 26.3
      months follow-up with a mean time to failure of 53.5 +/- 24.5 months. There were
      no significant differences in the lead failure-free Kaplan-Meier survival curve
      (p=0.77), deaths overall (p=0.17), or deaths categorised as sudden/cause unknown
      (p=0.54). CONCLUSIONS: Sprint Fidelis and Riata leads have a significant but
      comparable failure rate at 2.60% per year and 2.71% per year of follow-up
      respectively. The number of deaths in both groups is similar and no deaths have
      been identified as being related to lead failure in either cohort.

PMID- 23138014
TI  - Effects of ivabradine in patients with stable angina receiving beta-blockers
      according to baseline heart rate: an analysis of the ASSOCIATE study.
AB  - BACKGROUND: Any increase in heart rate (HR) during daily activities above the
      ischemic threshold may trigger myocardial ischemia. HR reduction with the If
      inhibitor ivabradine has been demonstrated to confer anti-ischemic and
      antianginal efficacy in patients with stable angina pectoris. This analysis of
      the ASSOCIATE trial assessed whether the anti-ischemic efficacy and safety of
      ivabradine were comparable in patients with baseline resting HRs above and below
      the median. METHODS: Patients with chronic stable angina pectoris were randomized
      to treatment with ivabradine (5 to 7.5mg bid) or placebo for 4 months, in
      addition to atenolol 50mg od. The effect of treatment on exercise tolerance test
      parameters was analyzed in two groups according to baseline HR: > 65 bpm (n=418)
      versus <= 65 bpm (n=436) (above and below the median, respectively). RESULTS:
      Ivabradine reduced resting HR in both groups with placebo-corrected reductions of
      -9.1 (95% CI -11.0 to -7.3; >65 bpm group) and -5.9 (95% CI -7.5 to -4.3; <= 65
      bpm group) (both P<0.001 versus placebo). Ivabradine reduced heart rate at all
      stages of exercise (all P<0.001). Improvements in exercise capacity (total
      exercise duration, time to limiting angina, angina onset, and 1-mm ST segment
      depression, all P<0.05) were recorded in both HR groups. There were no
      differences between the two groups in terms of safety. CONCLUSIONS: Ivabradine
      resulted in significant improvements in exercise capacity relative to placebo in
      patients with stable angina pectoris receiving beta-blocker therapy whether their
      resting HR was above or below 65 bpm.

PMID- 23138015
TI  - Transfer of eight phthalates through the milk chain--a case study.
AB  - This survey determined the levels of eight phthalates - i.e. dimethyl phthalate
      (DMP), diethyl phthalate (DEP), diisobutyl phthalate (DiBP), di-n-butyl phthalate
      (DnBP), benzylbutyl phthalate (BzBP), di(2-ethylhexyl) phthalate (DEHP),
      dicyclohexyl phthalate (DCHP) and di-n-octyl phthalate (DnOP) - in several
      Belgian milk and dairy products. Samples were obtained from various farms, a
      dairy factory and from different shops in order to investigate phthalate
      contamination "from farm to fork". At several stages in the milk chain, product
      contamination with phthalates - mostly DiBP, DnBP, BzBP and DEHP - was observed.
      At farm level, the mechanical milking process and the intake of phthalate
      containing feed by the cattle were found to be possible contamination sources. At
      industry and retail level, contact materials including packaging materials were
      additional contamination sources for phthalates in milk and dairy products.

PMID- 23138016
TI  - Biotransformation of fluorotelomer compound to perfluorocarboxylates in humans.
AB  - Levels of perfluorocarboxylates (PFCAs) in biological compartments have been
      known for some time but their transport routes and distribution patterns are not
      properly elucidated. The opinions diverge whether the exposure of the general
      population occurs indirect through precursors or direct via PFCAs. Previous
      results showed that ski wax technicians are exposed to levels up to 92 000
      ng/m(3) of 8:2 fluorotelomer alcohol (FTOH) via air and have elevated blood
      levels of PFCAs. Blood samples were collected in 2007-2011 and analyzed for C(4)
      C(18) PFCAs, 6:2, 8:2 and 10:2 unsaturated fluorotelomer acids (FTUCAs) and 3:3,
      5:3 and 7:3 fluorotelomer acids (FTCAs) using UPLC-MS/MS. Perfluorooctanoic acid
      (PFOA) was detected in levels ranging from 1.90 to 628 ng/mL whole blood (wb).
      Metabolic intermediates 5:3 and 7:3 FTCA were detected in all samples at levels
      up to 6.1 and 3.9 ng/mL wb. 6:2, 8:2 and 10:2 FTUCAs showed maximum levels of
      0.07, 0.64 and 0.11 ng/mL wb. Also, for the first time levels of PFHxDA and
      PFOcDA were detected in the human blood at mean concentrations up to 4.22 ng/mL
      wb and 4.25 ng/mL wb respectively. The aim of this study was to determine
      concentrations of PFCAs and FTOH metabolites in blood from ski wax technicians.

PMID- 23138017
TI  - Spatially explicit prioritization of human antibiotics and antineoplastics in
      Europe.
AB  - This paper presents a screening tool for the location-specific prioritization of
      human pharmaceutical emissions in Europe, based on risk quotients for the aquatic
      environment and human health. The tool provides direction towards either
      monitoring activities or additional research. Its application is illustrated for
      a set of 11 human antibiotics and 7 antineoplastics. Risk quotients for the
      aquatic environment were highest for levofloxacin, doxycycline and ciprofloxacin,
      located in Northern Italy (Milan region; particularly levofloxacin) and other
      densely populated areas in Europe (e.g. London, Krakow and the Ruhr area). Risk
      quotients for human health not only depend on pharmaceutical and location, but
      also on behavioral characteristics, such as consumption patterns. Infants in
      eastern Spain that consume locally produced food and conventionally treated
      drinking water were predicted to run the highest risks. A limited comparison with
      measured concentrations in surface water showed that predicted and measured
      concentrations are approximately within one order of magnitude.

PMID- 23138018
TI  - Perfluoroalkyl substances in human milk: a first survey in Italy.
AB  - Due to their widespread diffusion, perfluoroalkyl substances (PFASs) have been
      frequently found in the environment and in several animal species. It has been
      demonstrated that they can easily reach also humans, mainly through diet. Being
      lactation a major route of elimination of these contaminants, their occurrence in
      human milk is of particular interest, especially considering that it generally
      represents the unique food source for newborns. Perfluorooctane sulfonate (PFOS)
      and perfluorooctanoic acid (PFOA), the two most important compounds of this
      family, have been frequently found in human milk at variable concentrations, but
      still limited data are available. The present study, the first conducted in Italy
      capable to detect these pollutants at ultra-trace levels by UPLC-MS/MS, confirmed
      the role of lactation as a relevant source of exposure for breastfed children.
      The measured concentrations ranged between 15 and 288 ng/L for PFOS and between
      24 and 241 ng/L for PFOA. Moreover, mean concentrations and frequencies of both
      analytes resulted higher in milk samples provided by primiparous women,
      suggesting that the risk of intake might be higher for first-borns. Finally,
      comparing these results with previous data, PFOS gradual decrease over time since
      year 2000 was confirmed.

PMID- 23138019
TI  - Topical simvastatin accelerates wound healing in diabetes by enhancing
      angiogenesis and lymphangiogenesis.
AB  - Impaired wound healing is a major complication of diabetes. Recent studies have
      reported reduced lymphangiogenesis and angiogenesis during diabetic wound
      healing, which are thought to be new therapeutic targets. Statins have effects
      beyond cholesterol reduction and can stimulate angiogenesis when used
      systemically. However, the effects of topically applied statins on wound healing
      have not been well investigated. The present study tested the hypothesis that
      topical application of simvastatin would promote lymphangiogenesis and
      angiogenesis during wound healing in genetically diabetic mice. A full-thickness
      skin wound was generated on the back of the diabetic mice and treated with
      simvastatin or vehicle topically. Simvastatin administration resulted in
      significant acceleration of wound recovery, which was notable for increases in
      both angiogenesis and lymphangiogenesis. Furthermore, simvastatin promoted
      infiltration of macrophages, which produced vascular endothelial growth factor C
      in granulation tissues. In vitro, simvastatin directly promoted capillary
      morphogenesis and exerted an antiapoptotic effect on lymphatic endothelial cells.
      These results suggest that the favorable effects of simvastatin on
      lymphangiogenesis are due to both a direct influence on lymphatics and indirect
      effects via macrophages homing to the wound. In conclusion, a simple strategy of
      topically applied simvastatin may have significant therapeutic potential for
      enhanced wound healing in patients with impaired microcirculation such as that in
      diabetes.

PMID- 23138020
TI  - Potential of Ophiostoma piceae sterol esterase for biotechnologically relevant
      hydrolysis reactions.
AB  - The ascomycete Ophiostoma piceae produces a sterol esterase (OPE) with high
      affinity toward p-nitrophenol, glycerol, and sterol esters. Recently, this enzyme
      has been heterologously expressed in the methylotrophic yeast Pichia pastoris
      under the AOX1 methanol-inducible promoter (PAOX1) using sorbitol as co
      susbtrate, and the hydrolytic activity of the recombinant protein (OPE*) turned
      out to be improved from a kinetic point of view. In this study, we analyze the
      effects of sorbitol during the expression of OPE*, at first added as an
      additional carbon source, and methanol as inducer. The O. piceae enzyme was
      successfully used for PVAc hydrolysis, suggesting its potential applicability in
      recycled paper production to decrease stickies problems. 

PMID- 23138021
TI  - Can MRI-derived factors predict the survival in glioblastoma patients treated
      with postoperative chemoradiation therapy?
AB  - BACKGROUND: Advanced diagnostic and therapeutic developments may yield novel
      prognostic factors in patients with glioblastoma multiforme (GBM). PURPOSE: To
      validate the predictive values of pretreatment quantitative diffusion-weighted
      (DW) magnetic resonance imaging (MRI) and MRI performed within 72 h after surgery
      in patients with GBM. MATERIAL AND METHODS: Between January 2000 and September
      2009, 138 patients with GBM underwent postoperative chemoradiation therapy (chemo
      RT) and longitudinal MRI before surgery, in the early postoperative period, and
      at 1-month intervals thereafter. The role of the patient age, Karnofsky
      performance scale (KPS) score, minimum apparent diffusion coefficient (ADC) on
      pretreatment DW-MRI, and gross residual tumor on early postoperative MRI were
      assessed by factor analysis of overall survival (OS). Survival curves were
      calculated using the Kaplan-Meier method; the multivariate Cox's proportional
      hazards model was used to adjust for the influence of prognostic factors.
      Radiation Therapy Oncology Group-recursive partitioning analysis (RTOG-RPA)
      criteria were used to validate the predictive value of the MRI-derived factors.
      RESULTS: Substantial independent prognostic factors were the KPS score (hazard
      ratio [HR], 1.812), minimum ADC (HR, 2.365), and gross residual tumor (HR,
      1.777). Based on MRI-derived factors, we assigned the patients to different
      prognostic groups in the RTOG-RPA classification and grouped them according to
      the level of risk, i.e. a high-risk group with low minimum ADCs (<0.93 * 10(-3)
      mm(2)/s) with gross residual tumor and a low-risk group with high minimum ADCs
      (>=0.93 * 10(-3) mm(2)/s) without gross residual tumor; the other patients were
      assigned to the intermediate-risk group. Median OS for the low-, intermediate-,
      and high-risk groups were 28.2, 14.7, and 10.8 months, respectively (P < 0.001).
      CONCLUSION: The minimum ADC on pretreatment DW-MRI and gross residual tumor on
      early postoperative MRI can predict the survival in GBM patients treated with
      postoperative chemo-RT.

PMID- 23138022
TI  - F18-FDG PET-CT analyses of small peripheral adenocarcinoma of the lung.
AB  - BACKGROUND: Radiological discrimination of histologic subtypes of small
      peripheral adenocarcinoma of the lung is clinically important. Although there are
      many articles in which CT findings were used for this purpose, there are only a
      few reports on the capability of FDG PET-CT findings for histologic
      classification of this tumor. PURPOSE: To investigate the correlation between
      visual assessment or maximum standard uptake values (SUVmax) on F18-FDG PET-CT
      and histology grading of small peripheral adenocarcinoma of the lung. MATERIAL
      AND METHODS: Proportions of positive PET-CT diagnoses and SUVmax were
      retrospectively reviewed on 96 solitary pulmonary nodules of <=2 cm in 90
      consecutive patients. Tumors were classified into four groups according to
      Noguchi's classification (group 1 [n = 10], atypical adenomatous hyperplasia and
      type A tumors; group 2 [n = 12], type B tumors; group 3 [n = 42], type C tumors;
      group 4 [n = 32], types D, E, and F tumors). Proportions of positive PET-CT
      diagnoses and mean SUVmax of lesions among four groups were compared using trend
      tests to examine if there is a significant linear correlation with the
      progression of the histology grading of tumors. Then, an optimal threshold of
      SUVmax was proposed to best discriminate tumors of poor (groups 3 and 4) from
      good (groups 1 and 2) prognosis. RESULTS: There was a significant linear trend
      for both visual assessment (P < 0.01) and SUVmax (P < 0.01). A SUVmax of 0.42
      showed the highest accuracy of 84% with 95% sensitivity and 50% specificity for
      predicting tumors of poor prognosis. A SUVmax of 2.05 showed 100% specificity
      with 49% sensitivity, and 60% accuracy. Positive visual diagnoses showed accuracy
      of 83% with 90% sensitivity and 59% specificity. CONCLUSION: Visual assessment
      and SUVmax on PET-CT correlated well with the histology grading of small
      peripheral adenocarcinoma of the lung.

PMID- 23138023
TI  - Whole spine CT for evaluation of scoliosis in children: feasibility of sub
      milliSievert scanning protocol.
AB  - BACKGROUND: Optimization of CT radiation dose is important for children due to
      their higher risk of radiation-induced adverse effects. Anatomical structures
      with high inherent contrast, such as bones can be imaged at very low radiation
      doses by optimizing scan parameters. PURPOSE: To assess feasibility of sub
      milliSievert whole spine CT scanning protocol for evaluation of scoliosis in
      children. MATERIAL AND METHODS: With approval of the ethical board, we performed
      whole spine CT for evaluation of scoliosis in 22 children (age range, 3-18 years;
      mean age, 13 years; 13 girls, 9 boys) on a 128-slice dual source multidetector
      row CT scanner. Lowest possible quality reference mAs value (image quality factor
      for xy-z automatic exposure control or xyz-AEC, CARE Dose 4D) was selected on a
      per patient basis. Remaining parameters were held constant at 3.0:1 pitch, 128 *
      0.6 mm detector collimation, 115.2 mm table feed per gantry rotation, 100 kVp,
      and 1 and 3 mm reconstructed sections. Average mAs, projected estimated dose
      savings with AEC, computed tomography dose index volume (CTDI vol), and dose
      length product (DLP) were recorded. Artifacts were graded on a four-point scale
      (1, no artifacts; 4, severe artifacts). Ability to identify vertebral and
      pedicular contours, and measure pedicular width and degree of vertebral rotation
      was graded on a three-point scale (1, unacceptable; 3, excellent). RESULTS: All
      CT examinations were deemed as reliable for identifying vertebral and pedicular
      contours as well as for measuring pedicular width (5.9 +/- 1.6 mm) and degree of
      vertebral rotation (28.7 +/- 23.4 degrees ). Mean objective image noise and
      signal to noise ratio (SNR) were 57.5 +/- 21.5 and 4.7 +/- 2.3, respectively.
      With a mean quality reference mAs of 13, the scanner employed an average actual
      effective mAs of 10 +/- 3.8 (range, 6-18 mAs) with an estimated radiation dose
      saving of 43.5 +/- 16.3% with xyz-AEC compared with fixed mAs. The mean CTDI,
      DLP, and estimated effective doses were 0.4 +/- 0.1 mGy (0.2-0.7 mGy), 21 +/- 10
      mGy.cm (8-41 mGy.cm), and 0.3 +/- 0.1 mSv (0.12-0.64 mSv), respectively.
      CONCLUSION: Radiation dose for whole spine CT for evaluation of scoliosis in
      children can be minimized to less than one-third of a milliSievert while
      maintaining diagnostic image quality.

PMID- 23138024
TI  - Feline spermatozoa from fresh and cryopreserved testicular tissues have
      comparable ability to fertilize matured oocytes and sustain the embryo
      development after intracytoplasmic sperm injection.
AB  - Cryopreservation of testicular tissue associated with intracytoplasmic sperm
      injection (ICSI) is a critical tool that still needs to be explored for
      preserving the fertility of endangered species. Using the domestic cat as a model
      for wild felids, the study aimed at determining the effect of different
      cryoprotectants and freezing techniques (two-step freezing vs. controlled slow
      freezing) on the sperm quality (membrane and DNA integrity). Then, spermatozoa
      were extracted from frozen-thawed testicular tissues and used for ICSI to assess
      early gamete activation or developmental competence in vitro. The percentage of
      spermatozoa with intact plasma membrane was not different (P > 0.05) among
      nonfrozen control, glycerol-, and ethylene glycol-frozen tissues (63.2 +/- 2%,
      58.2 +/- 2.6%, 53.3 +/- 2.3%, respectively). However, these percentages were
      significantly lower (P < 0.05) in groups of dimethyl sulfoxide (46.3 +/- 3.3%)
      and 1,2 propanediol (44.3 +/- 2.9%) when compared with control. Conventional
      freezing combined with 5% (vol/vol) glycerol best preserved sperm membrane
      integrity (55.0 +/- 2.7%) when compared with other freezing techniques. The
      incidence of DNA fragmentation was found to be low (0.2%-1.1%) in all freezing
      protocols. After ICSI with frozen testicular spermatozoa, male and female gametes
      were asynchronously activated and the percentages of normal fertilization at 6,
      12, and 18 hours were 11.2%, 20.6%, and 22.1%, respectively. Metaphase II
      arrested oocytes containing or not a decondensed sperm head were predominantly
      found after ICSI with frozen testicular spermatozoa. Although two-pronucleus
      formation could be observed as soon as 6 hours post ICSI (10%), the rate
      increased dramatically after 12 and 18 hours post ICSI (17.2% and 19.5%,
      respectively). ICSI using frozen-thawed testicular spermatozoa yielded cleavage
      (32.7%), morula (6.5%), and blastocyst (4.4%) percentages similar to nonfrozen
      control (P > 0.05). It is concluded that conventional freezing technique with
      glycerol as a principle cryoprotectant is simplified and applicable for cat
      testicular tissue cryopreservation. We also demonstrate for the first time that
      feline spermatozoa derived from frozen-thawed testicular tissues retain their
      fertilizing ability and can be used to produce ICSI-derived embryos.

PMID- 23138025
TI  - Board Francais d'Orthodontie.

PMID- 23138027
TI  - Therapeutic thoughts on the treatment of sequellae of labial-alveolar-palatal
      clefts in adult patients-part 2.
AB  - With a worldwide incidence of 1/750 live births, facial clefts rank as the second
      most frequent congenital malformation. The term "sequelae" is used here to
      designate the conditions, which follow and are the result of labial-alveolar
      palatal clefts. Most sequelae stem in fact from primary treatment and not from
      the initial malformation. However, there is no consensus regarding a management
      protocol. Among the 201 European centers treating this type of malformation, 194
      different protocols are used for unilateral facial clefts alone! Unfortunately,
      primary surgery can trigger a wide range of harmful repercussions. It is for this
      reason that secondary surgery is called for, generally after the adolescent
      growth spurt. The aim is to correct the damage done by primary surgery, which can
      affect the nose, lips, teeth and jaws and impact functions such as speech,
      breathing and swallowing, as well as morphological and psychological development.
      Nonetheless, the children concerned are sometimes lost to treatment only to re
      emerge in adulthood, aware of the resultant defects and looking for facial
      esthetic improvement. The sequelae of labial-alveolar-palatal clefts take very
      different clinical forms according to whether the cleft has been treated or not
      and the type and timing of the procedures performed. The surgeon's experience
      will be paramount in the management of such cases, which draws heavily upon dento
      maxillo-facial orthopedics. In this context, we intend, in this paper, to propose
      modalities for the management of labial-alveolar-palatal clefts supported by
      information currently available in the literature. Management of labial-alveolar
      palatal clefts requires an interdisciplinary rather than the only
      multidisciplinary approach. The practitioner coordinating the management must,
      like an orchestra conductor, ensure both the rhythm and the tempo of the
      treatment. The rhythm will determine the choice of chronological protocol and the
      tempo will govern the timing and importance given to each of the specialists
      involved. Practices vary from country to country but the orthodontist may be
      called on to assume this responsibility.

PMID- 23138029
TI  - Electronic structure of the new Ni-based superconductor KNi2Se2.
AB  - The electronic structure of the newly discovered superconductor KNi(2)Se(2) is
      studied by first-principles calculations. Our results show that its ground state
      is a quasi-two-dimensional metal and the Fermi surface is contributed by the Ni
      3d and Se 4p states. These states determine the significant physical properties
      of the heavy-fermion superconductor KNi(2)Se(2), such as the heavy-fermion
      behavior and low superconducting transition temperature. Based on the multi
      orbital character of our calculation, we suggest that KNi(2)Se(2) may have a
      complicated superconducting multi-gap structure. The influence of the Coulomb
      interaction on the electronic structure and the 3d orbital character in this
      material is also investigated.

PMID- 23138030
TI  - 25-hydroxyvitamin D3 ameliorates periodontitis by modulating the expression of
      inflammation-associated factors in diabetic mice.
AB  - Periodontitis is a complication of diabetes mellitus, and the two diseases are
      highly associated with the dysfunction of inflammatory mediators. 25
      hydroxyvitamin D(3) (25(OH)D(3)) plays a pivotal role in inflammatory modulation,
      but little is known about its effects on the progression of diabetic
      periodontitis and the underlying mechanism. In this paper, we showed that
      25(OH)D(3) ameliorated experimental periodontitis in diabetic mice. The
      intraperitoneal administration of 25(OH)D(3) to streptozotocin-induced diabetic
      mice reduced fasting glucose and serum TNF-alpha levels, leading to decreased
      alveolar bone loss. Western blot analyses of gingival epithelia showed that
      vitamin D receptor (VDR) and protein tyrosine phosphatase N2 (PTPN2) were
      upregulated, while the expression of NF-kappaB and the phosphorylation of Janus
      family kinase 1 (JAK1) were attenuated upon 25(OH)D(3) treatment. These data may
      provide an explanation for the therapeutic benefits and anti-inflammatory effects
      of 25(OH)D(3). Our findings should have important implications for the clinical
      therapy of diabetic periodontitis.

PMID- 23138031
TI  - Characterization of ventricular depolarization and repolarization changes in a
      porcine model of myocardial infarction.
AB  - In this study, several electrocardiogram (ECG)-derived indices corresponding to
      both ventricular depolarization and repolarization were evaluated during acute
      myocardial ischemia in an experimental model of myocardial infarction produced by
      40 min coronary balloon inflation in 13 pigs. Significant changes were rapidly
      observed from minute 4 after the start of coronary occlusion, achieving their
      maximum values between 11 and 22 min for depolarization and between 9 and 12 min
      for repolarization indices, respectively. Subsequently, these maximum changes
      started to decrease during the latter part of the occlusion. Depolarization
      changes associated with the second half of the QRS complex showed a significant
      but inverse correlation with the myocardium at risk (MaR) estimated by
      scintigraphic images. The correlation between MaR and changes of the downward
      slope of the QRS complex, [Formula: see text], evaluated at the two more relevant
      peaks observed during the occlusion, was r = -0.75, p < 0.01 and r = -0.79, p <
      0.01 for the positive and negative deflections observed in [Formula: see text],
      temporal evolution, respectively. Repolarization changes, analyzed by evaluation
      of ST segment elevation at the main observed positive peak, also showed negative,
      however non-significant correlation with MaR: r = -0.34, p = 0.28. Our results
      suggest that changes evaluated in the latter part of the depolarization, such as
      those described by [Formula: see text], which are influenced by R-wave amplitude,
      QRS width and ST level variations simultaneously, correlate better with the
      amount of ischemia than other indices evaluated in the earlier part of
      depolarization or during the ST segment.

PMID- 23138032
TI  - A plethora of progenitors in the post-natal prostate.

PMID- 23138034
TI  - Magnetic resonance angiography of the posterior circulation.

PMID- 23138033
TI  - Use of varenicline for smoking cessation and risk of serious cardiovascular
      events: nationwide cohort study.
AB  - OBJECTIVE: To investigate whether varenicline is associated with an increased
      risk of serious cardiovascular events compared with another drug used for smoking
      cessation, bupropion. DESIGN: Nationwide historical cohort study. SETTING:
      Denmark, 2007-10. PARTICIPANTS: New users of varenicline (n = 17,926) and
      bupropion (n = 17,926). MAIN OUTCOME MEASURES: Individual level data on dispensed
      drug prescriptions, cardiovascular events, and potential confounders were linked
      between registries. Cox regression was used to estimate hazard ratios of
      cardiovascular events in analyses matched for propensity score. The primary
      outcomes at six months after start of treatment were acute coronary syndrome,
      ischaemic stroke, and cardiovascular death analysed individually and as a
      composite of any major event. RESULTS: There were 57 major cardiovascular events
      among varenicline users (6.9 cases per 1000 person years) compared with 60 events
      among bupropion users (7.1 cases per 1000 person years); the hazard ratio for any
      major event was 0.96 (95% confidence interval 0.67 to 1.39). Varenicline use was
      not associated with an increased risk of acute coronary syndrome (1.20, 0.75 to
      1.91), ischaemic stroke (0.77, 0.40 to 1.48), and cardiovascular death (0.51,
      0.13 to 2.02). In subgroup analyses, the risk of any major cardiovascular event
      was not significantly different between patients with and without a history of
      cardiovascular disease (1.24 (0.72 to 2.12) and 0.83 (0.51 to 1.36),
      respectively; P=0.29). CONCLUSIONS: This cohort study found no increased risk of
      major cardiovascular events associated with use of varenicline compared with
      bupropion for smoking cessation. On the basis of the upper confidence limit, the
      data allowed the exclusion of a 40% increased risk of the composite outcome of
      any major cardiovascular event. While the estimates were less precise for
      specific outcomes, any differences would be small in absolute terms.

PMID- 23138035
TI  - New marketing code for Indian drug companies favours the companies, critics say.

PMID- 23138036
TI  - Patients with type 1 diabetes are blocked from specialist services by NHS
      commissioning policies.

PMID- 23138037
TI  - Varenicline for smoking cessation.

PMID- 23138038
TI  - Protecting India's poorest from unaffordable medical bills.

PMID- 23138039
TI  - India plans universal screening of newborns amid logistical challenges.

PMID- 23138040
TI  - Implementing health care reform in US may still be difficult despite Obama win.

PMID- 23138041
TI  - Circle predicted "unprecedented" savings from running Hinchingbrooke, says
      watchdog.

PMID- 23138042
TI  - The re-election of US President Barack Obama.

PMID- 23138043
TI  - An examination of strategies for preventing workplace homicides committed by
      perpetrators that have a prior relationship with the workplace or its employees.
AB  - OBJECTIVE: To determine whether recommended robbery prevention strategies also
      protect against workplace homicide committed by a perpetrator who has a
      relationship with either the workplace or an employee (prior-relationship
      homicide). METHODS: A case-control study examining the relationship between
      recommended violence prevention strategies and prior-relationship workplace
      homicides in North Carolina was conducted. RESULTS: Workplaces located in an
      industrial park, employing minorities, reporting a history of violence, open
      night hours, or open 24 hours were more likely to experience prior-relationship
      homicide. Keeping entrances to the workplace locked when employees were present
      (OR = 0.36, 95% CI: 0.13, 0.99) and having at least one security device (OR =
      0.28, 95% CI: 0.10, 0.74) decreased the odds of prior-relationship homicide.
      CONCLUSIONS: Select strategies recommended to prevent robberies and subsequent
      violence may also afford protection against prior-relationship homicide.

PMID- 23138044
TI  - Sit-stand powered mechanical lifts in long-term care and resident quality
      indicators.
AB  - OBJECTIVE: To determine associations between long-term care powered mechanical
      lift (PML) availability and mobility-related resident outcomes. METHODS: Long
      term care directors of nursing (N = 271) nationwide gave facility information on
      the PML availability and the lifting policy to which we linked data on mobility
      related resident outcomes from the Centers for Medicare & Medicaid Services
      Minimum Data Set Quality Indicators. RESULTS: Four of six Centers for Medicare &
      Medicaid Services-derived resident indicators improved with the PML number but
      were maximal for the sit-stand lift use. In facilities with the fewest lifts, 16%
      of residents had pressure ulcers and 4% were bedfast. In facilities with the
      maximum number of lifts, only 10% had pressure ulcers (P = 0.000) and 2% were
      bedfast (P = 0.002). Although falls were more frequent with more lift use, this
      risk was blunted by a comprehensive safe lift program. CONCLUSION: The PML
      availability is associated with benefits to resident outcomes, and accompanying
      risks are mitigated by safe lift policies.

PMID- 23138045
TI  - Improving risk stratification--detecting physiological deterioration.

PMID- 23138047
TI  - Cortex-based inter-subject analysis of iEEG and fMRI data sets: application to
      sustained task-related BOLD and gamma responses.
AB  - Linking regional metabolic changes with fluctuations in the local electromagnetic
      fields directly on the surface of the human cerebral cortex is of tremendous
      importance for a better understanding of detailed brain processes. Functional
      magnetic resonance imaging (fMRI) and intra-cranial electro-encephalography
      (iEEG) measure two technically unrelated but spatially and temporally
      complementary sets of functional descriptions of human brain activity. In order
      to allow fine-grained spatio-temporal human brain mapping at the population
      level, an effective comparative framework for the cortex-based inter-subject
      analysis of iEEG and fMRI data sets is needed. We combined fMRI and iEEG
      recordings of the same patients with epilepsy during alternated intervals of
      passive movie viewing and music listening to explore the degree of local spatial
      correspondence and temporal coupling between blood oxygen level dependent (BOLD)
      fMRI changes and iEEG spectral power modulations across the cortical surface
      after cortex-based inter-subject alignment. To this purpose, we applied a simple
      model of the iEEG activity spread around each electrode location and the cortex
      based inter-subject alignment procedure to transform discrete iEEG measurements
      into cortically distributed group patterns by establishing a fine anatomic
      correspondence of many iEEG cortical sites across multiple subjects. Our results
      demonstrate the feasibility of a multi-modal inter-subject cortex-based
      distributed analysis for combining iEEG and fMRI data sets acquired from multiple
      subjects with the same experimental paradigm but with different iEEG electrode
      coverage. The proposed iEEG-fMRI framework allows for improved group statistics
      in a common anatomical space and preserves the dynamic link between the temporal
      features of the two modalities. 

PMID- 23138046
TI  - Novel dental adhesives containing nanoparticles of silver and amorphous calcium
      phosphate.
AB  - OBJECTIVES: Secondary caries is the main reason for restoration failure, and
      replacement of the failed restorations accounts for 50-70% of all restorations.
      Antibacterial adhesives could inhibit residual bacteria in tooth cavity and
      invading bacteria along the margins. Calcium (Ca) and phosphate (P) ion release
      could remineralize the lesions. The objectives of this study were to incorporate
      nanoparticles of silver (NAg) and nanoparticles of amorphous calcium phosphate
      (NACP) into adhesive for the first time, and to investigate the effects on dentin
      bond strength and plaque microcosm biofilms. METHODS: Scotchbond multi-purpose
      adhesive was used as control. NAg were added into primer and adhesive at 0.1% by
      mass. NACP were mixed into adhesive at 10%, 20%, 30% and 40%. Microcosm biofilms
      were grown on disks with primer covering the adhesive on a composite. Biofilm
      metabolic activity, colony-forming units (CFU) and lactic acid were measured.
      RESULTS: Human dentin shear bond strengths (n=10) ranged from 26 to 34 MPa;
      adding NAg and NACP into adhesive did not decrease the bond strength (p>0.1). SEM
      examination revealed resin tags from well-filled dentinal tubules. Numerous NACP
      infiltrated into the dentinal tubules. While NACP had little antibacterial
      effect, NAg in bonding agents greatly reduced the biofilm viability and metabolic
      activity, compared to the control (p<0.05). CFU for total microorganisms, total
      streptococci, and mutans streptococci on bonding agents with NAg were an order of
      magnitude less than those of the control. Lactic acid production by biofilms for
      groups containing NAg was 1/4 of that of the control. SIGNIFICANCE: Dental plaque
      microcosm biofilm viability and acid production were greatly reduced on bonding
      agents containing NAg and NACP, without compromising dentin bond strength. The
      novel method of incorporating dual agents (remineralizing agent NACP and
      antibacterial agent NAg) may have wide applicability to other dental bonding
      systems.

PMID- 23138048
TI  - Radicicol, an Hsp90 inhibitor, inhibits intestinal inflammation and leakage in
      abdominal sepsis.
AB  - BACKGROUND: Intestinal injury is a key feature in sepsis. Inhibitors of heat
      shock protein 90 (Hsp90) have been shown to exert protective effects in models of
      inflammation. Herein, we hypothesized that Hsp90 might regulate intestinal
      inflammation and leakage in abdominal sepsis. MATERIALS AND METHODS: Male C57BL/6
      mice were pretreated with radicicol (60 mg/kg), which is a specific inhibitor of
      Hsp90, prior to cecal ligation and puncture (CLP). Intravital fluorescence
      microscopy was used to quantify leukocyte-endothelium interactions in the colonic
      microcirculation 6 h after CLP. Colonic tissue was harvested to determine levels
      of myeloperoxidase, tumor necrosis factor-alpha and CXC chemokines. Intestinal
      injury was examined by histology. Intestinal barrier function was quantified by
      leakage of fluorescein isothiocyanate-dextran from the vascular system out into
      the abdominal cavity after intravenous injection. RESULTS: We found that
      radicicol significantly decreased CLP-induced leukocyte rolling and adhesion in
      colonic venules. Inhibition of Hsp90 reduced colonic levels of myeloperoxidase by
      24% in septic animals. Moreover, radicicol significantly decreased CLP-provoked
      formation of CXC chemokines but had no significant effect on tumor necrosis
      factor-alpha levels in the colon. Notably, Hsp90 inhibition significantly
      attenuated intestinal tissue injury evoked by CLP. Lastly, it was found that
      radicicol reduced sepsis-induced intestinal leakage by 43%. CONCLUSION: Our novel
      findings suggest that targeting Hsp90 protects against intestinal inflammation
      and leakage and might be a useful strategy to ameliorate intestinal failure in
      polymicrobial sepsis.

PMID- 23138050
TI  - [Metabolic syndrome and coronary artery disease].

PMID- 23138049
TI  - Revisiting early postinjury mortality: are they bleeding because they are dying
      or dying because they are bleeding?
AB  - BACKGROUND: Intense debate continues in the search of the optimal ratio of blood
      components to deliver preemptively in the critically injured patient anticipated
      to require a massive transfusion. A major challenge is distinguishing patients
      with refractory coagulopathy versus those with overwhelming injuries who will
      perish irrespective of blood component administration. The hypothesis of this
      clinical study is that a predominant number of early deaths from hemorrhage are
      irretrievable despite an aggressive transfusion policy. MATERIALS AND METHODS:
      During the 7-y period ending in December 2009, there were 772 in-hospital trauma
      deaths. Each of these deaths had been assigned a cause of death via concurrent
      review by the multidisciplinary hospital trauma quality improvement committee.
      Emergency department deaths and patients arriving from outside facilities were
      excluded from this study. RESULTS: Of the 382 patients (49.5% of total) who died
      secondary to acute blood loss, 84 (22.0%) survived beyond the ED; of these 84, 68
      (81%) were male, mean age was 31 y, and 30 (36%) sustained blunt trauma. Cause of
      death was determined to be exsanguination in 63 (75%), coagulopathy in 13 (15%),
      metabolic failure in 5 (6%), and indeterminate in 3 patients (4%). CONCLUSION:
      These data indicate that 75% of patients who succumb to postinjury acute blood
      loss are bleeding because they are dying rather than dying because they are
      bleeding. Conversely, only 13 (2%) of the hospital deaths were attributed to
      refractory coagulopathy. These critical facts need to be considered in designing
      studies to determine optimal massive transfusion protocols.

PMID- 23138051
TI  - [Giant left atrial myxoma presenting as acute myocardial infarction].
AB  - Myxomas are the most common type of benign cardiac tumor. The most frequent
      clinical presentations are symptoms resulting from atrioventricular valve
      obstruction or systemic embolization. Coronary embolization is a rare, although
      real and potentially fatal, complication of cardiac myxomas. We present a case
      report and review of the literature on this disease association. A 57-year-old
      woman was admitted to our coronary care unit with a diagnosis of non-ST elevation
      acute myocardial infarction. Transthoracic echocardiography showed a large left
      atrial mass attached to the interatrial septum, coral-like and with a friable
      appearance, suggestive of myxoma. Coronary angiography revealed no significant
      lesions and the patient underwent surgical excision of the mass, which
      histological study showed to be compatible with myxoma. The postoperative period
      was uneventful and the patient is doing well, with no recurrence of myxoma.

PMID- 23138052
TI  - [Metastatic tumor of the right ventricle: an unusual location of tumor
      involvement in laryngeal carcinoma].
AB  - Secondary tumors are much more frequent than primary tumors, but cardiac
      metastasis of laryngeal carcinoma is uncommon. The authors report the case of a
      71-year-old man, with a history of laryngeal carcinoma, admitted to the emergency
      room with symptoms of two weeks' evolution suggestive of respiratory infection.
      Due to lack of therapeutic response and progressive clinical deterioration, a
      transthoracic echocardiogram was performed which revealed a large infiltrating
      mass within the right ventricle, involving the apex, interventricular septum and
      free wall, not causing significant right ventricular outflow tract obstruction.
      Evaluation by computed tomography showed signs of widespread metastasis from the
      previously diagnosed laryngeal cancer.

PMID- 23138053
TI  - Performance and energy economics of mesophilic and thermophilic digestion in
      anaerobic hybrid reactor treating coal wastewater.
AB  - Two anaerobic hybrid AHRs (AHR), mesophilic (35  degrees C) and thermophilic (55 
      degrees C) were operated with coal wastewater at different hydraulic retention
      times (HRT) ranging from 3-0.5 to 3.12-0.6d with organic loading rates (OLR) of
      1.12-6.72 g L(-1) d(-1). Synthetic coal wastewater with an average chemical
      oxygen demand (COD) of 2240 mg L(-1) and phenolics concentration of 752 mg L(-1)
      was used as substrate. At each HRT, the thermophilic AHR gave a better
      performance, measured in terms of phenolics/COD removal and gas production. The
      specific methane yield was also higher for thermophilic AHR at each HRT compared
      to mesophilic one. The volatile fatty acid concentration in the effluent
      increased with the lowering of HRT. The Stover-Kincannon model was applicable at
      both temperatures and showed higher substrate utilization in thermophilic AHR.
      Energy economic study of the AHRs revealed that 11,938 MJ d(-1) more energy can
      be generated using thermophilic AHR than mesophilic.

PMID- 23138054
TI  - Optimization of a microbial fuel cell for wastewater treatment using recycled
      scrap metals as a cost-effective cathode material.
AB  - Microbial fuel cell (MFC) for wastewater treatment is still hindered by the
      prohibitive cost of cathode material, especially when platinum is used to
      catalyze oxygen reduction. In this study, recycled scrap metals could be used
      efficiently as cathode material in a specially-designed MFC. In terms of raw
      power, the scrap metals ranked as follows: W/Co > Cu/Ni > Inconel 718 > carpenter
      alloy; however, in terms of cost and long term stability, Inconel 718 was the
      preferred choice. Treatment performance--assessed on real and synthetic
      wastewater--was considerably improved either by filling the anode compartment
      with carbon granules or by operating the MFC in full-loop mode. The latter option
      allowed reaching 99.7% acetate removal while generating a maximum power of 36 W
      m(-3) at an acetate concentration of 2535 mg L(-1). Under these conditions, the
      energy produced by the system averaged 0.1 kWh m(-3) of wastewater treated.

PMID- 23138055
TI  - High titer ethanol production from SPORL-pretreated lodgepole pine by
      simultaneous enzymatic saccharification and combined fermentation.
AB  - Lodgepole wood chips were pretreated by sulfite pretreatment to overcome
      recalcitrance of lignocelluloses (SPORL) at 25% solids loading and 180  degrees C
      for 20 min with sulfuric acid and sodium bisulfite charges of 2.2 and 8 wt/wt% on
      an oven-dry wood basis, respectively. The pretreated wood chips were disk-milled
      with pretreatment spent liquor and water, and the solid fraction was separated
      from the liquor stream. The liquor was neutralized and concentrated through
      vacuum evaporation. Quasi-simultaneous enzymatic saccharification of the
      cellulosic solids and combined fermentation with the concentrated liquor was
      conducted at up to 20% total solids loading. Fed-batching of the solids
      facilitated liquefaction and saccharification, as well as managing instantaneous
      inhibitor concentrations. At a commercial cellulase (CTec2) loading of only 9 FPU
      or 0.06 mL/g untreated wood, a maximum ethanol titer of 47.4 g/L was achieved,
      resulting in a calculated yield of 285 L/tonne of wood using Saccharomyces
      cerevisiae YRH400 at 35  degrees C and pH 5.5.

PMID- 23138056
TI  - The kinetic analysis of the pyrolysis of agricultural residue under non
      isothermal conditions.
AB  - The study concerns the pyrolysis kinetics of agricultural wastes, corn straw (CS)
      and rice husk (RH). Thermogravimetric experiments were carried out in a
      thermogravimetric analyzer under inert conditions, and operated at different
      heating rates ranging from 5 to 40K/min. As the increment of heating rates, the
      variations of characteristic parameters from the TG-DTG curves were determined.
      Iso-conversional Starink approach and Avrami theory were used to evaluate the
      kinetic parameters, including apparent activation energy and reaction order. For
      the range of conversion fraction investigated (20-80%), the apparent activation
      energy of CS initially increased from 98.715 to 148.062 kJ/mol and then decreased
      to 144.387 kJ/mol afterwards, whilst the apparent activation energy of RH
      increased gradually from 50.492 to 88.994 kJ/mol. With varied temperatures (517
      697 K), the corresponding value of reaction order was increased from 0.288 and
      0.359 to 0.441 and 0.692, along with a decrease to 0.306 and 0.445, respectively.

PMID- 23138057
TI  - Hydrotreatment of bio-oil over Ni-based catalyst.
AB  - Inexpensive non-sulfided Ni-based catalysts were evaluated for hydrotreatments
      using phenol as model compound. HZSM-5, a zeolite with different ratio of Si/Al
      and gamma-Al(2)O(3) were impregnated with Ni(NO(3))(2) . 6H(2)O and calcined at
      450  degrees C. Conversion rates and product distribution for treatment of phenol
      at 160-240  degrees C in the presence of catalysts with nickel loads of 6, 10, 14
      and 17 wt.% were determined. Phenol conversion was highest (91.8%) at 240 
      degrees C in the presence of HZSM-5(Si/Al = 38) loaded with 10% Ni. When
      hydrotreatment was carried out with bio-oil obtained from pyrolysis of pine
      sawdust under the optimal conditions determined for phenol, the pH of bio-oil
      increased from 2.27 to 4.07, and the hydrogen content increased from 6.28 to 7.01
      wt.%. The decrease in acidity is desirable for the use of upgraded bio-oil.

PMID- 23138058
TI  - Removal of microelemental Cr(III) and Cu(II) by using soybean meal waste--unusual
      isotherms and insights of binding mechanism.
AB  - In the present study soybean meal (SBM) waste has been used for the removal
      Cr(III) and Cu(II) from aqueous solutions. Effect of variable parameters
      including pH, contact time, biomass dose and initial concentration of metal ions
      were studied. Biosorption kinetics was very fast and the kinetics data were
      successfully modeled using nonlinear pseudo-second-order model. A series of
      isotherm experiments revealed that pH 5 favored Cr(III) and Cu(II) biosorption
      and the affinity order of SBM was Cu(II) > Cr(III). Biosorption mechanism was
      confirmed by the functional group blocking, FTIR and scanning electron
      microscopy/energy-dispersive X-ray results. The biosorption mechanism was due to
      (i) ion-exchange, (ii) chelation by carboxyl and hydroxyl groups present on the
      SBM surface, (iii) further precipitation of metal ions on the surface of biomass.
      Our results revealed that SBM could be employed as an effective and low-cost
      biosorbent for removal of Cr(III) and Cu(II) from contaminated effluents.

PMID- 23138059
TI  - Biofiltration of a mixture of ethylene, ammonia, n-butanol, and acetone gases.
AB  - This study describes cleaning of a waste gas stream using bench scale biofilters
      (BFs) or biotrickling filters (BTFs). The gas stream contained a mixture of
      acetone, n-butanol, methane, ethylene, and ammonia, and was diverted uniformly to
      six biofilters and four biotrickling filters. The biofilters were packed with
      either perlite (BF-P), polyurethane foam (BF-F), or a mixture of compost, wood
      chips, and straw (BF-C), whereas the biotrickling filters contained either
      perlite (BTF-P) or polyurethane foam (BTF-F). Experimental results showed that
      both BFs and BTFs packed with various media were able to achieve complete removal
      of highly soluble compounds such as acetone, n-butanol, and ammonia of which the
      dimensionless Henry's constants (H) are less than 0.01. Methane was not removed
      due to its extreme insolubility (H>30). However, the ethylene (H ~ 9) removal
      efficiencies depended on trickle water flow rates, media surface areas, and
      ammonia gas levels.

PMID- 23138060
TI  - Evaluation of Laminaria-based microbial fuel cells (LbMs) for electricity
      production.
AB  - Marine algae represents a sustainable feedstock in microbial fuel cells (MFCs)
      due to its low water and energy requirements for cultivation, higher capacity to
      sequester carbondioxide, and high carbohydrate content. Two-compartment MFCs were
      evaluated under batch-fed mode using Laminaria saccharina as the model for algae
      based electron donor, and mixed microbial consortia as the biocatalyst, in the
      anode compartment. The Laminaria-based MFCs (LBMs) were studied with three
      different pretreatment conditions for the L. saccharina: (i) autoclaving (Auto),
      (ii) microwave irradiation (Micro), and (iii) as received treatment (No-Treat). A
      control was setup to establish base line performance for two-compartment MFCs
      using glucose as the electron donor in the anode. The performance of LBMs (250
      mW/m(2) and 900 mA/m(2)) was on par with glucose-based MFCs. AC impedance
      analysis revealed that the charge transfer resistance was at least 50-fold higher
      than the corresponding ohmic losses in both LBMs and glucose-based MFCs.

PMID- 23138061
TI  - Detection and quantitation of lipid in the microalga Tetraselmis subcordiformis
      (Wille) Butcher with BODIPY 505/515 staining.
AB  - BODIPY 505/515, a lipophilic bright green fluorescent dye was tested for lipid
      detection in the microalga Tetraselmis subcordiformis. A concentration of 0.28
      MUg ml(-1) and staining for 6 min was optimal. Lipid bodies stained with
      BODIPY505/515 had a characteristic green fluorescence. Their volumes were
      determined using the sphere volume formula. Lipid accumulation under different
      nitrogen concentrations was analyzed. With an increase in NaNO(3) concentration
      from 0 to 240 mg L(-1), the maximum algal concentration increased from 8.23 +/-
      0.62 (* 10(5) cells ml(-1)) to 1.61 +/- 0.13 (*10(6) cells ml(-1)), while the
      maximum volume of intracellular neutral lipid decreased from 9.78 +/- 1.77 MUm(3)
      cell(-1) to 6.00 +/- 0.59 MUm(3) cell(-1). A comparison of the lipid contents
      measured by BODIPY 505/515 staining and the gravimetric method showed a positive
      correlation coefficient of R(2) = 0.93. BODIPY 505/515 staining is a promising
      method in lipid quantitation in T. subcordiformis.

PMID- 23138062
TI  - Long-term operation of biomass-to-liquid systems coupled to gasification and
      Fischer-Tropsch processes for biofuel production.
AB  - Long-term operation of the biomass-to-liquid (BTL) process was conducted with a
      focus on the production of bio-syngas that satisfies the purity standards for the
      Fischer-Tropsch (FT) process. The integrated BTL system consisted of a bubbling
      fluidized bed (BFB) gasifier (20 kW(th)), gas cleaning unit, syngas compression
      unit, acid gas removing unit, and an FT reactor. Since the raw syngas from the
      gasifier contains different types of contaminants, such as particulates,
      condensable tars, and acid gases, which can cause various mechanical problems or
      deactivate the FT catalyst, the syngas was purified by passing through cyclones,
      a gravitational dust collector, a two-stage wet scrubber (packing-type), and a
      methanol absorption tower. The integrated system was operated for 500 h over
      several runs, and stable operating conditions for each component were achieved.
      The cleaned syngas contained no sulfur compounds (under 1 ppmV) and satisfied the
      requirements for the FT process.

PMID- 23138063
TI  - Production of recombinant Bacillus subtilis chitosanase, suitable for
      biosynthesis of chitosan-oligosaccharides.
AB  - Chitosanases are enzymes that catalyse the hydrolysis of the beta-1,4 glycosidic
      bond of chitosan. One of the most promising applications of this enzyme is for
      the bioconversion of chitosan into value-added chitosan-oligosaccharides (COS).
      GH46 chitosanase (Csn) from Bacillus subtilis 168 was expressed in Escherichia
      coli by fusing the gene encoding mature Csn to the E. coli OmpA signal peptide
      sequence. The recombinant enzyme was secreted into the culture supernatant. The
      recombinant Csn showed high specific activity and stability over a wide range of
      pH. The enzyme was >100 times more thermostable in the presence of the substrate,
      with a half-life time of activity (tau(1/2)) of approximately 20 h at 50  degrees
      C and pH 5.5. Efficient bioconversion of chitosan into different mixtures of COS,
      using crude culture supernatant containing secreted enzyme was demonstrated.

PMID- 23138064
TI  - Evaluation of integrated anaerobic/aerobic fixed-bed sequencing batch biofilm
      reactor for decolorization and biodegradation of azo dye acid red 18: comparison
      of using two types of packing media.
AB  - Two integrated anaerobic/aerobic fixed-bed sequencing batch biofilm reactor (FB
      SBBR) were operated to evaluate decolorization and biodegradation of azo dye Acid
      Red 18 (AR18). Volcanic pumice stones and a type of plastic media made of
      polyethylene were used as packing media in FB-SBBR1 and FB-SBBR2, respectively.
      Decolorization of AR18 in both reactors followed first-order kinetic with respect
      to dye concentration. More than 63.7% and 71.3% of anaerobically formed 1
      naphthylamine-4-sulfonate (1N-4S), as one of the main sulfonated aromatic
      constituents of AR18 was removed during the aerobic reaction phase in FB-SBBR1
      and FB-SBBR2, respectively. Based on statistical analysis, performance of FB
      SBBR2 in terms of COD removal as well as biodegradation of 1N-4S was
      significantly higher than that of FB-SBBR1. Spherical and rod shaped bacteria
      were the dominant species of bacteria in the biofilm grown on the pumice stones
      surfaces, while, the biofilm grown on surfaces of the polyethylene media had a
      fluffy structure.

PMID- 23138065
TI  - Biochemical features and bioethanol production of microalgae from coastal waters
      of Pearl River Delta.
AB  - This study describes identification, cultivation, monitoring of carbohydrate
      accumulation and bioethanol production from microalgal strains from the coastal
      waters of Pearl River Delta. Eighteen identified strains belong to the families
      Chlorellaceae, Scotiellocystoidaceae, Neochloridaceae, Selenastraceae and
      Scenedesmaceae. Of isolated strains Mychonastes afer PKUAC 9 and Scenedesmus
      abundans PKUAC 12 were selected for further biomass and ethanol production
      analysis. Comparison of three cultivation modes (stationary, shaken and aerated)
      resulted in the highest biomass productivity obtained for aerated cultures that
      yielded 0.09 g and 0.11 g dry weight per day per litre of medium for M. afer
      PKUAC 9 and S. abundans PKUAC 12, respectively. Carbohydrate accumulation
      monitored by FTIR showed that early stationary phase is optimal for biomass
      harvest. Microalgal biomass was successfully used as a carbohydrate feedstock for
      fermentative bioethanol production. S. abundans PKUAC 12 was superior feedstock
      for bioethanol production when pre-treated with the combination of dilute acid
      treatment and cellulase.

PMID- 23138066
TI  - Sensing of plant hydrolysate-related phenolics with an aaeXAB::luxCDABE
      bioreporter strain of Escherichia coli.
AB  - A bioluminescent Escherichia coli bioreporter strain to detect hydrolysate
      related phenolics was developed by cloning the aaeXAB promoter from E. coli
      upstream of the luxCDABE genes. E. coli str. DH5alpha carrying this plasmid
      (pDMA3) was responsive to sub-inhibitory concentrations of plant hydrolysate
      related phenolics, such as ferulic and vanillic acids, responding to these
      compounds at concentrations as low as 9.8 and 4.9 mg/L, respectively. Experiments
      with a mixture of the compounds showed similar responses as with single compound
      tests, with a minimum detectable concentration of 19.5mg/L. Finally, tests using
      rice straw hydrolysates were conducted, with E. coli str. DH5alpha/pDMA3 showing
      a maximum induction of 33-fold and a minimum detectable phenolic concentration of
      9.3mg/L, based upon Folin-Ciocalteu's reagent. These results demonstrate that
      this bioreporter maintains its sensitivity even with hydrolysate samples and that
      it can be potentially applied within biofuel industries to detect phenolics
      present within plant hydrolysates.

PMID- 23138067
TI  - Lipid production by Rhodosporidium toruloides Y2 in bioethanol wastewater and
      evaluation of biomass energetic yield.
AB  - The oleaginous yeast Rhodosporidium toruloides Y2 was employed to remove waste
      nutrients from bioethanol wastewater while simultaneously producing biomass
      enriched in microbial lipids. Under optimal conditions, the COD degradation
      ratio, biomass and lipid content reached 72.3%, 3.8 g/l and 34.9%, respectively.
      For accelerating biomass and lipid accumulation, different feeding strategies of
      substrate were conducted. The biomass and lipid production increased by 39.5% and
      53.8%, respectively, when glucose at 1.2g/(ld) was added during the last three
      days of the cultivation. An equation was established to estimate biomass
      energetic yield. Under optimal conditions, the biomass energetic yield was 50.9%
      and an increase of 26.0% was obtained by feeding glucose at 1.2g/(ld) during the
      last three days. The fatty acid composition of the lipids was similar to that
      from plant oils and other microbial lipids, and could thus be used as raw
      material for feed additives and biodiesel production.

PMID- 23138068
TI  - Temperature modulation of fatty acid profiles for biofuel production in nitrogen
      deprived Chlamydomonas reinhardtii.
AB  - This study investigated the changes in the fatty acid content and composition in
      the nitrogen-starved Chlamydomonas reinhardtii starchless mutant, BAF-J5, grown
      at different temperatures. The optimal temperature for vegetative growth under
      nitrogen sufficient conditions was found to be 32  degrees C. Shifting
      temperature from 25 to 32  degrees C, in conjunction with nitrogen starvation,
      resulted in BAF-J5 storing the maximum quantity of fatty acid (76% of dry cell
      weight). Shifting to temperatures lower than 25  degrees C, reduced the total
      amount of stored fatty acid content and increased the level of desaturation in
      the fatty acids. The optimal fatty acid composition for biodiesel was at 32 
      degrees C. This study demonstrates how a critical environmental factor, such as
      temperature, can modulate the amount and composition of fatty acids under
      nitrogen deprivation and reduce the requirement for costly refining of biofuels.

PMID- 23138069
TI  - Lowering the applied potential during successive scratching/re-inoculation
      improves the performance of microbial anodes for microbial fuel cells.
AB  - Microbial anodes were formed under polarisation at -0.2V/SCE on smooth graphite
      plate electrodes with paper mill effluents. Primary, secondary and tertiary
      biofilms were formed by a successive scratching and re-inoculation procedure. The
      secondary and tertiary biofilms formed while decreasing the polarisation
      potential allowed the anodes to provide current density of 6A/m(2) at -0.4V/SCE.
      In contrast, applying -0.4V/SCE initially to form the primary biofilms did not
      lead to the production of current. Consequently, the scratching/re-inoculation
      procedure combined with progressive lowering of the applied potential revealed an
      efficient new procedure that gave efficient microbial anodes able to work at low
      potential. The observed progressive pH drift to alkaline values above 9 explained
      the open circuit potentials as low as -0.6 V/SCE. The remarkable performance of
      the electrode at alkaline pH was attributed to the presence of Desulfuromonas
      acetexigens as the single dominant species in the tertiary microbial anodes.

PMID- 23138070
TI  - Performance of a flat panel reactor in the continuous culture of microalgae in
      urban wastewater: prediction from a batch experiment.
AB  - A laboratory-scale flat panel photobioreactor was operated for the continuous
      growth of Scenedesmus obliquus and consequent removal of nutrients in wastewater.
      This study develops a simple model by which biomass values in continuous
      operation can be predicted from kinetic growth parameters obtained from a shorter
      batch experiment. Based on this study, biomass concentrations and productivities
      in continuous operation can be successfully predicted as a function of the
      specific hydraulic retention time (HRT) assumed. Considerable biomass production
      and nutrient uptake from wastewater were achieved in the experiment. Optimum
      operating conditions for the reactor depend on the particular objective: the
      maximization of biomass production and carbon dioxide biofixation involves a HRT
      of 2 MU(-1) (specific growth rate), whereas efficient nutrient removal involves a
      HRT as close as possible to MU(-1) (as long as discharges comply fully with the
      parameters set); alternatively biomass intended for biodiesel or biogas
      production would involve a HRT > 2 MU(-1).

PMID- 23138071
TI  - Squeezing of magnetic flux in nanorings.
AB  - We study superconducting and non-superconducting nanorings and look for non
      classical features of magnetic flux passing through nanorings. We show that the
      magnetic flux can exhibit purely quantum properties in some peculiar states with
      quadrature squeezing. We identify a subset of Gazeau-Klauder states in which the
      magnetic flux can be squeezed and, within tailored parameter regimes, quantum
      fluctuations of the magnetic flux can be maximally reduced.

PMID- 23138072
TI  - Comparative study of various pretreatment reagents on rice husk and structural
      changes assessment of the optimized pretreated rice husk.
AB  - The performance of alkalis (NaOH and Ca(OH)2) and acids (H2SO4, HCl, H3PO4,
      CH3COOH, and HNO3) in the pretreatment of rice husk was screened, and a suitable
      reagent was assessed for subsequent optimization using response surface
      methodology. From the assessment, HCl that hydrolysed rice husk well was
      optimized with three parameters (HCl loading, pretreatment duration, and
      temperature) using Box-Behnken Design. The optimized condition (0.5% (w/v) HCl
      loading, 125  degrees C, 1.5 h) is relatively mild, and resulted in ~22.3mg
      TRS/ml hydrolysate. The reduced model developed has good predictability, where
      the predicted and experimental results differ by only 2%. The comprehensive
      structural characterization studies that involved FT-IR, XRD, SEM, and BET
      surface area determination showed that the pretreated rice husk consisted mainly
      of cellulose and lignin. Compared to untreated rice husk, pretreated rice husk
      possessed increased pore size and pore volume, which are expected to be
      beneficial for fungal growth during fermentation.

PMID- 23138073
TI  - Virtual simulation training using the Storz C-HUB to support distance airway
      training for the Spanish Medical Corps and NATO partners.
AB  - In medicine, the advancement of new technologies creates challenges to providers
      both in learning and in maintaining competency in required skills. For those
      medical providers located in remote environments, access to learning can be even
      more formidable. This work describes a collaboration created to facilitate the
      use of new communication technologies in providing distance training and support
      to health care personnel deployed in remote areas.

PMID- 23138074
TI  - Personal health records: retrieving contextual information with Google Custom
      Search.
AB  - Ubiquitous personal health records, which can accompany a person everywhere, are
      a necessary requirement for ubiquitous healthcare. Contextual information related
      to health events is important for the diagnosis and treatment of disease and for
      the maintenance of good health, yet it is seldom recorded in a health record. We
      describe a dual cellphone-and-Web-based personal health record system which can
      include 'external' contextual information. Much contextual information is
      available on the Internet and we can use ontologies to help identify relevant
      sites and information. But a search engine is required to retrieve information
      from the Web and developing a customized search engine is beyond our scope, so we
      can use Google Custom Search API Web service to get contextual data. In this
      paper we describe a framework which combines a health-and-environment 'knowledge
      base' or ontology with the Google Custom Search API to retrieve relevant
      contextual information related to entries in a ubiquitous personal health record.

PMID- 23138075
TI  - Successes and failures of using the cell phone as a main mode of communication
      between participants and facilitators from a distance: an innovative method of
      training rural health facility managers in Papua New Guinea.
AB  - Rural Health Facility Management Training is a training program developed by the
      National Department of Health in collaboration with AUSAID through the office of
      the Capacity Building Service Centre. The purpose of the training is to train
      officers-in-charge who did not acquire knowledge and skills of managing a health
      facility. As part of this study, it is essential to assess whether the cell phone
      is a better mode of communication between the participants and the facilitators
      compared with other modes of communication from a distance. The study used the
      cross-sectional method to collect 160 samples from 12 provinces and the
      statistical software Stata (version 8) was used to analyse the data. The results
      showed that mobile coverage is not very effective in most rural areas, though, it
      is efficient and accessible. Furthermore, it is expensive to make a call compared
      with sending text massages. In spite of the high cost involved, most health
      managers prefer to use the cell phone compared to normal post, email, or fax.
      This clearly shows that the mobile phone is a better device for distant learning
      in rural Papua New Guinea compared to other modes of communication.

PMID- 23138076
TI  - Telemedicine support of maternal and newborn health to remote provinces of
      Mongolia.
AB  - The telemedicine approach is a very much relevant and effective strategy for the
      Mongolian context of a huge geographical area with a sparse population and huge
      disparities in quality and access to health services. Through this initiative, it
      was possible to strengthen the capacity of service providers to provide timely
      and appropriate care, especially to mothers with pregnancy and childbirth
      complications. All the way through this network, health staff had easy access to
      information and support from experts; this improved access to knowledge is a
      positive benefit of the program. The early detection of pregnancy complications
      and timely management with the distance consultation of an expert team had
      contributed significantly to the reduction of maternal and newborn morbidity and
      mortality in project-selected provinces compared to non-project areas. The
      effective use of a modern telemedicine approach has been demonstrated as being
      effective in addressing the remoteness and rural-urban discrepancy in the quality
      of health care in Mongolia.

PMID- 23138077
TI  - Can a novel smartphone application detect periodic limb movements?
AB  - BACKGROUND: Periodic limb movements (PLMs) are repetitive, stereotypical and
      unconscious movements, typically of the legs, that occur in sleep and are
      associated with several sleep disorders. The gold standard for detecting PLMs is
      overnight electromyography which, although highly sensitive and specific, is time
      and labour consuming. The current generation of smart phones is equipped with tri
      axial accelerometers that record movement. AIM: To develop a smart phone
      application that can detect PLMs remotely. METHOD: A leg movement sensing
      application (LMSA) was programmed in iOS 5x and incorporated into an iPhone 4S
      (Apple INC.). A healthy adult male subject underwent simultaneous EMG and LMSA
      measurements of voluntary stereotypical leg movements. The mean number of leg
      movements recorded by EMG and by the LMSA was compared. RESULTS: A total of 403
      leg movements were scored by EMG of which the LMSA recorded 392 (97%). There was
      no statistical difference in mean number of leg movements recorded between the
      two modalities (p = 0.3). CONCLUSION: These preliminary results indicate that a
      smart phone application is able to accurately detect leg movements outside of the
      hospital environment and may be a useful tool for screening and follow up of
      patients with PLMs.

PMID- 23138078
TI  - Randomised controlled trial of an in-home monitoring intervention to improve
      health outcomes for type 2 diabetes: study protocol.
AB  - Type 2 diabetes is a leading cause of death and morbidity and is a health
      priority in Australia. This randomised controlled trial will explore whether
      remote access to clinical care, supported by telehealth technologies over high
      speed broadband, leads to improved diabetes control in a way that benefits
      patients, carers and clinicians and improves the overall health system. People in
      the intervention arm of the trial will receive additional diabetes care from a
      care coordinator nurse via an in-home broadband communication device that can
      capture clinical measures, provide regular health assessments and videoconference
      with other health professionals when required. Patients in the control arm of the
      trial will receive usual care from their GP and participate in the clinical
      measurement and quality of life components of the evaluation. The trial
      evaluation will include biomedical, psychological, self-management and quality of
      life measures. Data on utilisation rates and satisfaction with the technology
      will be collected and cost -effectiveness analyses undertaken. The role of this
      technology in health care reform will be explored.

PMID- 23138079
TI  - Targeting zero non-attendance in healthcare clinics.
AB  - Non-attendance represents a significant cost to many health systems, resulting in
      inefficiency, wasted resources, poorer service delivery and lengthened waiting
      queues. Past studies have considered extensively the reasons for non-attendance
      and have generally concluded that the use of reminder systems is effective.
      Despite this, there will always be a certain level of non-attendance arising from
      unforeseeable and unpreventable circumstances, such as illness or accidents,
      leading to unfilled appointments. This paper reviews current approaches to the
      non-attendance problem, and presents a high-level approach to fill last minute
      appointments arising out of unforeseeable non-attendance. However, no single
      approach will work for all clinics and implementation of these ideas must occur
      at a local level. These approaches include use of social networks, such as
      Twitter and Facebook, as a communication tool in order to notify prospective
      patients when last-minute appointments become available. In addition,
      teleconsultation using video-conferencing technologies would be suitable for
      certain last-minute appointments where travel time would otherwise be inhibiting.
      Developments of new and innovative technologies and the increasing power of
      social media, means that zero non-attendance is now an achievable target. We hope
      that this will lead to more evidence-based evaluations from the implementation of
      these strategies in various settings at a local level.

PMID- 23138080
TI  - Design of a large scale community-based self-management system for diabetes
      mellitus.
AB  - This paper presents the ongoing development of a community based, self-management
      system for diabetes mellitus, which incorporates web-based, SMS and mobile
      terminal functionalities. SMS represents the first stage of our system
      development as it is widely available on all mobile phones, convenient and
      becoming increasingly popular. We discuss past findings and the need for such a
      system, as well as design, implementation and system architecture. Poor self
      management of diabetes is associated with progression into more complex health
      issues, manifesting as a significant public health burden and impacting
      negatively on an individual's quality of life. This approach recognizes that
      telehealth systems will play an increasingly pertinent role in health systems
      worldwide.

PMID- 23138081
TI  - The telegraph and the beginnings of telemedicine in Australia.
AB  - The history of telemedicine is at times presented to commence in the 20th
      century. Events in Central Australia in 1874 show that the history goes further
      back, when the newly constructed telegraph played an important telemedicine role
      not only in enabling care for a wounded person, but also in uniting a dying man
      with his wife 2000 kilometres away. Innovation with the tools at hand has proven
      to be effective to bridge the tyranny of distance in the delivery of health care.

PMID- 23138082
TI  - Delivering healthcare cost-effectively using available technology.
AB  - This paper identifies ways technology, including telehealth, can be utilised to
      reduce health delivery costs whilst providing the highest possible standard of
      care.

PMID- 23138083
TI  - A proposal to design a Location-based Mobile Cardiac Emergency System (LMCES).
AB  - Healthcare for elderly people has become a vital issue. The Wearable Health
      Monitoring System (WHMS) is used to manage and monitor chronic disease in elderly
      people, postoperative rehabilitation patients and persons with special needs.
      Location-aware healthcare is achievable as positioning systems and
      telecommunications have been developed and have fulfilled the technology needed
      for this kind of healthcare system. In this paper, the researchers propose a
      Location-Based Mobile Cardiac Emergency System (LMCES) to track the patient's
      current location when Emergency Medical Services (EMS) has been activated as well
      as to locate the nearest healthcare unit for the ambulance service. The location
      coordinates of the patients can be retrieved by GPS and sent to the healthcare
      centre using GPRS. The location of the patient, cell ID information will also be
      transmitted to the LMCES server in order to retrieve the nearest health care
      unit. For the LMCES, we use Dijkstra's algorithm for selecting the shortest path
      between the nearest healthcare unit and the patient location in order to
      facilitate the ambulance's path under critical conditions.

PMID- 23138084
TI  - Using Twitter for prenatal health promotion: encouraging a multivitamin habit
      among college-aged females.
AB  - Half of the pregnancies in the United States are unplanned and the highest rate
      of these unplanned pregnancies occurs in young women aged 18-24y. Serious birth
      defects, such as those that affect the neural tube, occur early in pregnancy,
      most of the time before a woman knows she is pregnant. These neural tube defects
      can be reduced by 50-72% with an adequate daily intake of folic acid. In
      continuing the research on how to effectively communicate the important benefits
      of folic acid to young women, this study sought to investigate the use of social
      media as a tool for health promotion. Young women are considered the 'power
      users' of social media and the current study uses Twitter as a vehicle for
      multivitamin promotion messages due to the ability to quickly share content and
      the potential to attract viral attention through re-tweets.

PMID- 23138085
TI  - Automated NFC enabled rural healthcare for reliable patient record maintainance.
AB  - Body sensor networks can be used for health monitoring of patients by expert
      medical doctors, in remote locations like rural areas in developing countries,
      and can also be used to provide medical aid to areas affected by natural
      disasters in any part of the world. An important issue to be addressed, when the
      number of patients is large, is to reliably maintain the patient records and have
      simple automated mobile applications for healthcare helpers to use. We propose an
      automated healthcare architecture using NFC-enabled mobile phones and patients
      having their patient ID on RFID tags. It utilizes NFC-enabled mobile phones to
      read the patient ID, followed by automated gathering of healthcare vital
      parameters from body sensors using Bluetooth, analyses the information and
      transmits it to a medical server for expert feedback. With limited hospital
      resources and less training requirement for healthcare helpers through simpler
      applications, this automation of healthcare processing can provide time effective
      and reliable mass health consultation from medical experts in remote locations.

PMID- 23138086
TI  - The effect of post traumatic stress disorders on rehabilitation among combat
      wounded veterans.
AB  - In June 2008 the Congressionally Directed Medical Research Program provided a
      grant to the Research Foundation at the James A Haley Veterans Hospital in Tampa,
      Florida to provide care for wounded veterans from Operation Enduring Freedom
      (Afghanistan) and Operation Iraqi Freedom (OEF/OIF). The telerehabilitation for
      OEF/OIF returnees with mild or moderate combat related Traumatic Brain Injury
      (TBI) has as its objectives 1) care coordination for wounded veterans using
      distance technology via the internet and 2) monitoring of physical and mental
      health outcomes using a variety of instruments. A total of 75 veterans were
      enrolled in the study. Our initial findings indicate that 1) Functional
      capabilities measured by locomotion and mobility appear to have stabilized among
      our cohort of veterans while deficiencies in cognition (memory, problem solving),
      psychosocial adjustment (anger, emotional status) and problems in integrating
      into society pose challenges 2) Those with comorbid PTSD appear to linger in
      employability and ultimate integration into society as compared to those without
      the diagnosis 3) Individualized treatment pathways are needed for rehabilitation
      and ultimate integration into society.

PMID- 23138087
TI  - Personal health records: mobile biosensors and smartphones for developing
      countries.
AB  - A target of telehealth is to maintain or improve the health of people outside the
      normal healthcare infrastructure. A modern paradigm in healthcare, and one which
      fits perfectly with telehealth, is "person self-monitoring", and this fits with
      the concept of "personal health record" (PHR). One factor in maintaining health
      is to monitor physiological parameters; this is of course especially important in
      people with chronic maladies such as diabetes or heart disease. Parameters to be
      monitored include blood pressure, pulse rate, temperature, weight, blood glucose,
      oxygen saturation, electrocardiogram (ECG), etc. So one task within telehealth
      would be to help monitor an individual's physiological parameters outside of
      healthcare institutions and store the results in a PHR in a way which is
      available, comprehensible and beneficial to the individual concerned and to
      healthcare providers. To date many approaches to this problem have been
      fragmented - emphasizing only part of the problem - or proprietary and not freely
      verifiable. We describe a framework to approach this task; it emphasizes the
      implementation of standards for data acquisition, storage and transmission in
      order to maximize the compatibility among disparate components, e.g. various PHR
      systems. Data from mobile biosensors is collected on a smartphone using the IEEE
      11073 standard where possible; the data can be stored in a PHR on the phone
      (using standard formats) or can be converted in real-time into more useful
      information in the PHR, which is based on the International Classification for
      Primary Care (ICPC2e). The phone PHR data or information can be uploaded to a
      central online PHR using either the Wi-Fi or GSM transmission protocol together
      with the Continuity of Care Record message format (CCR, ASTM E2369).

PMID- 23138088
TI  - High definition 3D telemedicine: the next frontier?
AB  - Evidence from the literature indicates that the degree of immersion often
      referred to as the "sense of being there" experienced by clinicians and patients
      is a factor in the success of tele-health installations. High definition and 3D
      telemedicine offers a compelling mechanism to achieve a sense of immersion and
      contribute to an enhanced quality of use. This article surveys HD3D trials in
      tele-health and concludes that the way HD3D is integrated into telemedicine
      depends on the clinical, organisational and technological context. In some
      settings real time HD3D is not so desirable whereas asynchronous transmission of
      HD3D images and videos is highly desirable.

PMID- 23138089
TI  - Home care and technology: a case study.
AB  - Health care aides (HCAs) are the backbone of the home care system and provide a
      range of services to people who, for various reasons related to chronic
      conditions and aging, are not able to take care of themselves independently. The
      demand for HCA services will increase and the current HCA supply will likely not
      keep up with this increasing demand without fundamental changes in the current
      environment. Information and communication technology (ICT) can address some of
      the workflow challenges HCAs face. In this project, we conducted an ethnographic
      study to document and analyse HCAs' workflows and team interactions. Based on our
      findings, we designed an ICT tool suite, integrating easily available existing
      and newly developed (by our team) technologies to address these issues. Finally,
      we simulated the deployment of our technologies, to assess the potential impact
      of these technological solutions on the workflow and productivity of HCAs, their
      healthcare teams and client care.

PMID- 23138090
TI  - Towards an international electronic repository and virtual laboratory of open
      data and open-source software for telehealth research: comparison of
      international, Australian and Finnish privacy policies.
AB  - Health data includes all content related to health in all data formats, document
      types, information systems, publication media and languages from all specialties,
      organisations, regions, states and countries. Capabilities to share, integrate
      and compare these data contents, clinical trial results and other evaluation
      outcomes together with telehealth applications for data processing are critical
      to accelerate discovery and its diffusion to clinical practice. However, the same
      ethical and legal frameworks that protect privacy hinder this open data and open
      source code approach and the issues accumulate if moving data across national,
      regional or organisational borders. This can be seen as one of the reasons why
      many telehealth applications and health-research findings tend to be limited to
      very narrow domains and global results are lacking. The aim of this paper is to
      take steps towards establishing an international electronic repository and
      virtual laboratory of open data and open-source code for research purposes by
      comparing international, Australian and Finnish frameworks. The frameworks seem
      to be fundamentally similar; they apply the principles of accountability and
      adequacy to using and disclosing personal data. Their requirements to inform data
      subjects about the purposes of data collection and use before the dataset is
      collected, assure that individuals are no longer identifiable and to destruct
      data when the research activities are finished make sharing data and even
      secondary data difficult. Using the Internet or cloud services for sharing
      without proper approvals by ethics committees is technically not allowed if the
      data are stored in another country. The research community needs to overcome
      these barriers and develop a virtual laboratory, which operates on distributed
      data repositories. This empowers the community by enabling systematic evaluations
      of new technologies and research hypotheses on a rich variety of data and against
      existing applications, and subsequent tracking of quality improvements in time.

PMID- 23138091
TI  - An SMS-based HIV/AIDS education and awareness model for rural areas in Papua New
      Guinea.
AB  - Access to basic healthcare in many parts of Papua New Guinea (PNG) remains a
      challenge partly because the majority of the population is thinly scattered
      across a geographically rugged country. The major health problems in PNG pertain
      to malaria, tuberculosis and diarrheal diseases while HIV has reached epidemic
      levels. The proliferation of the mobile phone technology in PNG has been
      unprecedented since the introduction of competition in the sector in July 2007.
      Users in rural areas now access the mobile phone signal making it their preferred
      form of modern communications medium. This paper introduces an SMS-based HIV/AIDS
      education, awareness and information dissemination model for a predominantly
      rural-based PNG society.

PMID- 23138092
TI  - Viability of healthcare service delivery alternatives for the Australian mining
      sector.
AB  - The changing and demanding nature of the mining workforce in rural and remote
      Australia brings unique challenges to the delivery of healthcare services. In an
      attempt to control costs whilst delivering cost effective and quality healthcare,
      new models of delivery must be considered. For a workforce that is fly-in/fly
      out, the provision of healthcare is problematic given the lack of consistency in
      location. A cost-benefit framework is analysed comparing three models of service
      provision using travel to a major location, locum services and remote health
      monitoring. Ultimately, new models of care must be considered to address the
      issues of increasing workforce turnover, to cater for rising healthcare costs,
      and to improve the health of such communities.

PMID- 23138093
TI  - A videoconferencing tool acting as a home-based healthcare monitoring robot for
      elderly patients.
AB  - Currently, healthcare costs associated with aging at home can be prohibitive if
      individuals require continual/periodical supervision and assistance because of
      Alzheimer's disease. Open-source tools and videoconferencing tools are attracting
      more significant organizations; it has been observed that another way to reduce
      medical care costs is to reduce the length of the patient's hospitalization and
      reinforce home sanitary support by medical professionals with family care givers.
      Videoconferencing has been around for a while and presently this technology is
      the leading way in reducing healthcare costs, thus making medical care more
      available and convenient for both doctors and patients. This article portrays how
      the videoconferencing tool can be utilized to improve communication practices for
      patient monitoring using a Robot Companion. SWOT analysis method is also
      presented in a form of a summary and was utilized to evaluate the user's point of
      view.

PMID- 23138094
TI  - Telemonitoring of medication adherence in patients with major mental illness:
      watching the patient as well as the pills.
AB  - Many patients with major mental illness do not take their medication. This leads
      to repeated relapses. Some of these patients are managed by clinicians who visit
      the patient seven days a week long term and supervise their taking of medication.
      This paper explores the design and implementation of an Android telemonitoring
      application to supervise patients taking medication in their homes.

PMID- 23138098
TI  - Alpha thalassaemia and extended alpha globin genes in Sri Lanka.
AB  - The alpha-globin genes were studied in nine families with unexplained hypochromic
      anaemia and in 167 patients with HbE beta thalassaemia in Sri Lanka. As well as
      the common deletion forms of alpha(+) thalassaemia three families from an ethnic
      minority were found to carry a novel form of alpha(0) thalassaemia, one family
      carried a previously reported form of alpha(0) thalassaemia, --(THAI), and five
      families had different forms of non-deletional thalassaemia. The patients with
      HbE beta thalassaemia who had co-inherited alpha thalassaemia all showed an
      extremely mild phenotype and reduced levels of HbF and there was a highly
      significant paucity of alpha(+) thalassaemia in these patients compared with the
      normal population. Extended alpha gene arrangements, including alphaalphaalpha,
      alphaalphaalphaalpha and alphaalphaalphaalphaalpha, occurred at a low frequency
      and were commoner in the more severe phenotypes of HbE beta thalassaemia. As well
      as emphasising the ameliorating effect of alpha thalassaemia on HbE beta
      thalassaemia the finding of a novel form of alpha(0) thalassaemia in an ethnic
      minority, together with an unexpected diversity of forms of non-deletion alpha
      thalassaemia in Sri Lanka, further emphasises the critical importance of micro
      mapping populations for determining the frequency of clinically important forms
      of the disease.

PMID- 23138099
TI  - Population genetic data of 30 autosomal indels in Central Spain and the Basque
      Country populations.
AB  - Samples from 71 unrelated Central Spain individuals and 60 Basque Country
      autochthonous individuals were typed with the Investigator DIPplex kit (30
      biallelic autosomal mini-indels and amelogenin) and their allele frequencies were
      determined. Results demonstrated the assumption of independence within and
      between the loci analyzed. Different partially silent alleles were observed for
      the locus HLD97 (rs17238892) produced by a neighboring SNP (A/G), located 61 bp
      downstream from the main indel site as shown by sequencing analysis.

PMID- 23138100
TI  - A risk-benefit analysis of factor V Leiden testing to improve pregnancy outcomes:
      a case study of the capabilities of decision modeling in genomics.
AB  - PURPOSE: We sought to assess the benefits, risks, and personal utility of factor
      V Leiden mutation testing to improve pregnancy outcomes and to assess the utility
      of decision-analytic modeling for complex outcomes in genomics. METHODS: We
      developed a model to evaluate factor V Leiden testing among women with a history
      of recurrent pregnancy loss, including heparin therapy during pregnancy in
      mutation-positive women. Outcomes included venous thromboembolism, major bleeds,
      pregnancy loss, maternal mortality, and quality-adjusted life-years. RESULTS:
      Factor V Leiden testing in a hypothetical cohort of 10,000 women led to 7 fewer
      venous thromboembolic events, 90 fewer pregnancy losses, and an increase of 17
      major bleeding events. Small improvements in quality-adjusted life-years were
      largely attributable to reduced mortality but also to improvements in health
      related quality of life. However, sensitivity analyses indicate large variance in
      results due to data uncertainty. Furthermore, the complexity of outcomes limited
      our ability to fully capture the repercussions of testing in the quality-adjusted
      life-year measure. CONCLUSION: Factor V Leiden testing involves tradeoffs between
      clinical and personal utility, and additional effectiveness data are needed for
      heparin use to prevent pregnancy loss. Decision-analytic methods offer somewhat
      limited value in assessing these tradeoffs, suggesting that evaluation of complex
      outcomes will require novel approaches to appropriately capture patient-centered
      outcomes.Genet Med 2013:15(5):374-381.

PMID- 23138101
TI  - Rapid diversification in Australia and two dispersals out of Australia in the
      globally distributed bee genus, Hylaeus (Colletidae: Hylaeinae).
AB  - Hylaeus is the only globally distributed colletid bee genus, with subgeneric and
      species-level diversity highest in Australia. We used one mitochondrial and two
      nuclear genes to reconstruct a phylogeny using Bayesian analyses of this genus
      based on species from Australia, Asia, Africa, Europe, Hawai'i, the New World and
      New Zealand. Our results concord with a ca. 30Mya Hylaeus crown age inferred by
      earlier studies, and we show that Hylaeus originated in Australia. Our phylogeny
      indicates only two dispersal events out of Australia, both shortly after the
      initial diversification of extant taxa. One of these dispersals was into New
      Zealand with only a minor subsequent radiation, but the second dispersal out of
      Australia resulted in a world-wide distribution. This second dispersal and
      radiation event, combined with very extensive early radiation of Hyleaus in
      Australia, poses a conundrum: what kinds of biogeographical and ecological
      factors could simultaneously drive global dispersal, yet strongly constrain
      further successful migrations out of Australia when geographical barriers appear
      to be weak? We argue that for hylaeine bees movement into new niches and enemy
      free spaces may have favoured initial dispersal events, but that subsequent
      dispersals would not have entailed the original benefits of new niche space.

PMID- 23138104
TI  - Commentary on "Inhibitory effect of the antimalarial agent artesunate on collagen
      induced arthritis in rats through nuclear factor kappa B and mitogen-activated
      protein kinase signaling pathway".

PMID- 23138103
TI  - Translating the basic knowledge of mitochondrial functions to metabolic therapy:
      role of L-carnitine.
AB  - Mitochondria play important roles in human physiological processes, and
      therefore, their dysfunction can lead to a constellation of metabolic and
      nonmetabolic abnormalities such as a defect in mitochondrial gene expression,
      imbalance in fuel and energy homeostasis, impairment in oxidative
      phosphorylation, enhancement of insulin resistance, and abnormalities in fatty
      acid metabolism. As a consequence, mitochondrial dysfunction contributes to the
      pathophysiology of insulin resistance, obesity, diabetes, vascular disease, and
      chronic heart failure. The increased knowledge on mitochondria and their role in
      cellular metabolism is providing new evidence that these disorders may benefit
      from mitochondrial-targeted therapies. We review the current knowledge of the
      contribution of mitochondrial dysfunction to chronic diseases, the outcomes of
      experimental studies on mitochondrial-targeted therapies, and explore the
      potential of metabolic modulators in the treatment of selected chronic
      conditions. As an example of such modulators, we evaluate the efficacy of the
      administration of L-carnitine and its analogues acetyl and propionyl L-carnitine
      in several chronic diseases. L-carnitine is intrinsically involved in
      mitochondrial metabolism and function as it plays a key role in fatty acid
      oxidation and energy metabolism. In addition to the transportation of free fatty
      acids across the inner mitochondrial membrane, L-carnitine modulates their
      oxidation rate and is involved in the regulation of vital cellular functions such
      as apoptosis. Thus, L-carnitine and its derivatives show promise in the treatment
      of chronic conditions and diseases associated with mitochondrial dysfunction but
      further translational studies are needed to fully explore their potential.

PMID- 23138105
TI  - Genome-wide comparison of two RNA-stabilizing reagents for transcriptional
      profiling of peripheral blood.
AB  - Peripheral whole blood is relatively easily obtained for monitoring gene
      expression for biomarker discovery using transcriptomic platforms such as genome
      wide microarrays. However, whole blood provides challenges caused by sensitivity
      for ex vivo incubation and overrepresentation of globin mRNAs. We compared the
      performance of 2 commercial whole blood preservation methods, TEMPUS (Applied
      Biosystems, Foster City, CA) and PAXgene (PreAnalytiX, Qiagen BD, Valencia, CA),
      using 2 RNA amplification protocols and high-density microarrays. Performance of
      commercial globin mRNA reduction protocol also was studied. Human peripheral
      blood samples collected with TEMPUS and PAXgene Blood RNA tubes were amplified
      with the RiboAmp OA 1 Round RNA Amplification Kit (Arcturus; Applied Biosystems)
      and the Affymetrix (Santa Clara, CA) small sample protocol. Affymetrix globin
      reduction protocol was applied for total RNA samples. Samples amplified with
      RiboAmp were hybridized on Illumina Sentrix HumanRef-8 Expression BeadChips
      (Illumina Inc, San Diego, CA) and subjected to statistical analyses. RiboAmp mRNA
      amplification did not notably amplify globin mRNA that is overrepresented in RNA
      isolated by both TEMPUS and PAXgene preservation. Enzymatic depletion of globin
      transcript reduced the quality of total RNA and is thus not recommendable.
      Microarray analysis showed acceptable correlation within and between the RNA
      preservation methods, but altogether 443 transcripts were differentially
      expressed between RNA samples preserved in TEMPUS and PAXgene tubes. We
      demonstrated that the 2 tested blood RNA-preservation methods combined with
      RiboAmp mRNA amplification may be used for microarray experiments without the
      need for a prior globin RNA reduction. However, because genes involved in immune
      cell functions and gene regulatory pathways were differentially expressed as a
      result of the technical bias between the preservation methods, they should not be
      used in the same analytic setting.

PMID- 23138106
TI  - Au-supported Pt-Au mixed atomic monolayer electrocatalyst with ultrahigh specific
      activity for oxidation of formic acid in acidic solution.
AB  - Au-supported Pt-Au mixed atomic monolayer electrocatalyst was prepared by
      underpotential deposition of Cu on Au and then redox replacement with noble metal
      atoms, which shows an ultrahigh Pt-mass (or Pt-area) normalized specific
      electrocatalytic activity of 102 mA MUg(Pt)(-1) (124 mA cm(Pt)(-2)) for oxidation
      of formic acid in acidic aqueous solution.

PMID- 23138107
TI  - Relationships between black tea consumption and key health indicators in the
      world: an ecological study.
AB  - OBJECTIVES: The aim of this study was to investigate potential statistical
      relationships between black tea consumption and key health indicators in the
      world. The research question is: Does tea consumption is correlated with one or
      more epidemiological indicators? DESIGN: Ecological study using a systematic data
      mining approach in which the unit of the analysis is a population of one country.
      SETTING: Six variables, black tea consumption data and prevalence data of
      respiratory diseases, infectious diseases, cancer, cardiovascular diseases and
      diabetes, have been studied at a global level. PARTICIPANTS: Data from 50
      participating countries in the World Health Survey were investigated.   PRIMARY
      AND SECONDARY OUTCOMES MEASURES:  Level of statistical relationships between
      variables. RESULTS: Principal component analysis established a very high
      contribution of the black tea consumption parameter on the third axis (81%). The
      correlation circle confirmed that the 'black tea' vector was negatively
      correlated with the diabetes vector and was not correlated with any of the other
      four health indicators. A linear correlation model then confirmed a significant
      statistical correlation between high black tea consumption and low diabetes
      prevalence. CONCLUSIONS: This innovative study establishes a linear statistical
      correlation between high black tea consumption and low diabetes prevalence in the
      world. These results are consistent with biological and physiological studies
      conducted on the effect of black tea on diabetes and confirm the results of a
      previous ecological study in Europe. Further epidemiological research and
      randomised studies are necessary to investigate the causality.

PMID- 23138108
TI  - Induction heating studies of dextran coated MgFe2O4 nanoparticles for magnetic
      hyperthermia.
AB  - MgFe(2)O(4) nanoparticles with sizes around 20 nm have been prepared by a
      combustion method and functionalized with dextran for their possible applications
      in magnetic particle hyperthermia. The induction heating study of these
      nanoparticles at different magnetic field amplitudes, from 6.7 kA m(-1) to 26.7
      kA m(-1), showed self-heating temperature rise up to 50.25  degrees C and 73.32 
      degrees C (at 5 mg mL(-1) and 10 mg mL(-1) concentrations in water respectively)
      which was primarily thought to be due to hysteresis losses activated by an AC
      magnetic field. The dextran coated nanoparticles showed a maximum specific
      absorption rate (SAR) of about 85.57 W g(-1) at 26.7 kA m(-1) (265 kHz). Dextran
      coated nanoparticles at concentrations below 1.8 mg mL(-1) exhibit good viability
      above 86% on mice fibroblast L929 cells. The results suggest that combustion
      synthesized MgFe(2)O(4) nanoparticles coated with dextran can be used as
      potential heating agents in magnetic particle hyperthermia. Uncoated and dextran
      coated samples were characterized by X-ray diffraction (XRD), transmission
      electron microscopy (TEM) and vibrating sample magnetometry (VSM), Fourier
      transform infrared spectroscopy (FTIR), thermogravimetric-differential thermal
      analysis (TG-DTA) and zeta potential-DLS studies.

PMID- 23138109
TI  - Targeted quantum dots fluorescence probes functionalized with aptamer and peptide
      for transferrin receptor on tumor cells.
AB  - Quantum dots (QDs) fluorescent probes based on oligonucleotide aptamers and
      peptides with specific molecular recognition have attracted much attention. In
      this paper, CdSe/ZnS QDs probes for targeted delivery to mouse and human cells
      using aptamer GS24 and peptide T7 specific to mouse/human transferrin receptors
      were developed. Capillary electrophoresis analyses indicated that the optimal
      molar ratios of QDs to aptamer or peptide were 1:5. Fluorescence and confocal
      microscope imaging revealed QD-GS24 and QD-T7 probes were able to specifically
      recognize B16 cells and HeLa cells respectively. Quantitative flow cytometry
      analysis indicated the transportation of QD-GS24 or QD-T7 into cells could be
      promoted by corresponding free transferrin. Transmission electron microscopy
      confirmed the uptake of probes in cells and the effective intracellular delivery.
      MTT assay suggested the cytotoxicity of probes was related to the surface ligand,
      and aptamer GS24 (or peptide T7) could reduce the cytotoxicity of probes to a
      certain degree. The study has great significance for preparing QDs fluorescent
      probes using non-antibody target molecules.

PMID- 23138110
TI  - Drugs: the third rail of US politics.

PMID- 23138111
TI  - Transcriptional regulation of episodic glucocorticoid secretion.
AB  - Circadian and ultradian variations of basal glucocorticoid secretion and
      transient elevations during stress are essential for homeostasis. Using intronic
      qRT-PCR to measure changes in primary transcript (hnRNA) we have shown that
      secretory events induced by stress or ACTH injection are followed by episodic
      increases in transcription of rate limiting steroidogenic proteins, such as
      steroidogenic acute regulatory protein (StAR), cytochrome P450 side chain
      cleavage and melanocortin receptor associated protein. These transcriptional
      episodes imply rapid turnover of steroidogenic proteins and the need of de novo
      synthesis following each secretory event. In addition to episodic ACTH secretion,
      it is likely that intracellular feedback mechanisms at the adrenal fasciculata
      level contribute to the generation of episodes of transcription. The time
      relationship between activation and translocation of the CREB co-activator,
      transducer of regulated CREB activity (TORC) to the nucleus preceding
      transcriptional episodes suggest the involvement of TORC in the transcriptional
      activation of StAR and other steroidogenic proteins.

PMID- 23138113
TI  - A survey of transfusion practices in pediatric hematopoietic stem cell transplant
      patients.
AB  - Until recovery of hematopoiesis, pediatric hematopoietic stem cell transplant
      (HSCT) patients are dependent on red blood cell and platelet transfusions to
      avoid the complications associated with anemia and thrombocytopenia,
      respectively. Despite the fact that these patients are high utilizers of blood
      components, there are no evidence-based guidelines regarding optimal transfusion
      practices in this patient population. A web-based survey was designed to examine
      current transfusion thresholds used by institutions that perform pediatric HSCT.
      This survey was sent to department directors identified through the Children's
      Oncology Group directory with a response rate of 69%. The majority of
      institutions use 8 g/dL as the hemoglobin threshold for red blood cell
      transfusions (60%), but a significant minority use 7 g/dL (25%). With respect to
      platelet transfusion thresholds, 47% of respondents report using 20*10/L and 44%
      use 10*10/L. Respondents were also asked about specific clinical scenarios that
      would prompt an increase in a patient's threshold. This survey revealed that
      there is variation in transfusion practices among pediatric HSCT institutions
      with respect to both baseline transfusion threshold and what prompts an increase
      in threshold. Future clinical trials are needed to determine optimal transfusion
      thresholds in pediatric HSCT patients, which can lead to improved standardization
      in practices.

PMID- 23138114
TI  - 6-Mercaptopurine-induced recurrent acute pancreatitis in children with acute
      lymphoblastic leukemia/lymphoma.
AB  - Two children with acute lymphoblastic leukemia/lymphoma developed recurrent acute
      pancreatitis during treatment; the etiology was presumed to be secondary to 6
      mercaptopurine (6MP). Both had no further attacks after discontinuation of 6MP.
      Acute pancreatitis secondary to 6MP is extremely rare in acute leukemia/lymphoma
      although it has been reported in patients with other conditions like inflammatory
      bowel disease; the reason for this difference is not clearly understood. 

PMID- 23138112
TI  - Investigation of peripubertal expression of Lin28a and Lin28b in C57BL/6 female
      mice.
AB  - Genome-wide association studies recently identified 32 loci that associate with
      the age at menarche (AAM) in humans. Because the locus most robustly associated
      with AAM is in/near LIN28B, the goal of this study was to investigate how the
      Lin28 pathway might modulate pubertal timing by examining expression of Lin28b,
      and its homologue, Lin28a, across the pubertal transition in female mice.
      Quantitative reverse-transcriptase PCR data indicate that, prior to the onset of
      puberty, expression of both Lin28b and Lin28a decreases in the ovary, while
      expression of only Lin28a decreases in the hypothalamus; the expression of Lin28a
      increases after the onset of puberty in the pituitary. Immunohistochemistry in
      ovarian tissue verified that Lin28a protein levels decreased in parallel with
      gene expression. Although these data do not demonstrate cause and effect, they do
      suggest that decreased expression of Lin28a/Lin28b may facilitate the transition
      into puberty, consistent with previous data showing that overexpression of Lin28a
      in transgenic mice leads to delayed puberty. In addition, although Lin28b and/or
      Lin28a expression significantly decreased prior to puberty, neither Let-7a nor
      Let-7g miRNA levels changed significantly, raising the possibility that some
      effects of Lin28b and Lin28a within the hypothalamic-pituitary-gonadal (HPG) axis
      may be Let-7 miRNA independent. Subsequent studies, such as tissue and age
      specific modulation of Lin28b and Lin28a expression, could determine whether the
      expression patterns observed are responsible for modulating the onset of puberty
      and delineate further the role of this pathway in the HPG axis.

PMID- 23138115
TI  - A single-institution retrospective cases series of childhood undifferentiated
      embryonal liver sarcoma (UELS): success of combined therapy and the use of
      orthotopic liver transplant.
AB  - BACKGROUND/INTRODUCTION: Undifferentiated embryonal liver sarcoma (UELS) makes up
      9% to 15% of all malignant liver tumors in children. UELS is characteristically
      diagnosed between the ages of 6 and 10 years and presents with abdominal pain,
      vomiting, and an abdominal mass. There is currently no standardized treatment for
      UELS except attempt at complete surgical resection. There have been only about
      150 cases of UELS reported in the literature all with historically poor overall
      survival of <37.5% at 5 years. This report is one of the largest single
      institution reports of UELS consisting of 5 patients over 2 decades. The purpose
      of this study is to characterize presentation and to report treatment success in
      UELS in children, adolescents, and young adults and the use of liver
      transplantation and, lastly, to suggest a use of positron emission
      tomography/computed tomography (PET/CT) in monitoring of this disease process.
      METHODS: We conducted an Institutional Review Board-approved retrospective chart
      review. Data were collected from UELS patients younger than 21 years seen at the
      University of California Los Angeles over the past 20 years (January 2001 to
      September 2011). Descriptive analysis was conducted including multiple parameters
      of patient demographics, tumor characteristics, treatment modalities, and
      morbidity and mortality. RESULTS: Five patients with UELS were identified.
      Patients initially presented with fever, abdominal pain, or nausea. Ages ranged
      from 10 to 19 years old (median age 13 y old), and there was a 4:1 male-to-female
      predominance. Tumor size ranged from 6 to 22 cm in largest diameter. One patient
      presented with metastatic disease to the lungs and heart and 1 patient recurred 2
      years from diagnosis with bilateral paraspinal masses. Treatment included local
      control surgery with neoadjuvant and adjuvant chemotherapy with an
      anthracycline/alkylating agent combination. One patient with recurrent and
      refractory disease achieved local control with an orthotopic liver
      transplantation (OLT). Metastatic disease was controlled with surgery and
      radiation therapy. 18-Fluorodeoxyglucose PET/CT was a useful imaging tool for
      judging response to therapy with complete loss of metabolic activity in tumor
      after neoadjuvant chemotherapy in 2 representative cases. Although follow-up is
      short for some patients, overall survival in these 5 patients was 100% with
      follow-up ranging from 21 to 68 months. Disease-free survival ranged from 8 to 46
      months with no patients with residual disease. CONCLUSIONS: UELS is an aggressive
      high-grade primary liver sarcoma with high metastatic potential. This report
      represents one of the largest single-institution studies of UELS. Using
      multimodality therapy, patients have achieved 100% overall survival even in the
      setting of extensive disease, metastases, and recurrence. In cases of
      unresectable primary tumor or recurrent and refractory disease isolated to the
      liver, OLT is a potential therapeutic option. We report success with adjuvant
      chemotherapy and complete surgical resection with OLT as an alternative in
      unresectable or refractory cases. We also suggest a possible utility of PET/CT in
      monitoring treatment response in this disease.

PMID- 23138116
TI  - Brain is not always the last fortress; osteosarcoma with large brain metastasis.
AB  - Osteosarcomas are the most common malignant primary bone tumors in children and
      adolescents. Brain metastases of osteosarcoma are very rare and carry a dismal
      prognosis. We report a case of chondroblastic osteosarcoma of right humerus
      presented with right frontal lobe metastasis in a 10-year-old girl with small
      pulmonary lesions.

PMID- 23138117
TI  - Outcome of modified St Jude total therapy 13A for childhood acute lymphoblastic
      leukemia in the southeast region of Turkey.
AB  - OBJECTIVE: To fill the gap in the current data on childhood acute lymphoblastic
      leukemia (ALL) in low-income and middle-income countries. METHODS: This study
      included 106 children between the ages of 1 and 17 years with newly diagnosed ALL
      monitored between 1999 and 2010. All the patients were treated with the modified
      St Jude Total 13A treatment plan at the Pediatric Hematology Clinic at Harran
      University. RESULTS: Sixty-eight (64.2%) patients were boys and 38 (35.8%) were
      girls. The median age at diagnosis was 5.9 +/- 3.7 years. Thirty-eight (35.8%)
      children were classified as standard risk, 53 (39.3%) were intermediate risk, and
      15 (14.2%) were high risk. Thirteen (12.3%) children died in induction before the
      remission date (43 d of remission induction). Of all the 93 (100%) patients who
      completed remission induction therapy and whose bone marrow were in remission, 5
      (4.7%) had a bone marrow relapse, 1 (0.9%) had a retinal relapse, and 5 (4.7%)
      had secondary acute myeloid leukemia. At a median follow-up of 44 months (range,
      0.36 to 135.5 mo), the estimated 5-year overall survival and event-free survival
      were 77.4 +/- 5% and 68.9 +/- 6.5%, respectively. The estimated 5-year overall
      survival for boys and girls was 76.5 +/- 6% and 65.8 +/- 8%, respectively (P =
      0.182). CONCLUSIONS: St Jude Total 13A treatment protocols to treat childhood ALL
      can be successfully adapted, which suggests that such an approach may be useful
      in low socioeconomic regions; however, it should be noted that secondary leukemia
      can occur at a high rate.

PMID- 23138118
TI  - Generation of induced pluripotent stem cells from human amniotic fluid cells by
      reprogramming with two factors in feeder-free conditions.
AB  - The ectopic expression of transcription factors for reprogramming human somatic
      cells to a pluripotent state represents a valuable resource for the development
      of in vitro-based models for human disease and has great potential in
      regenerative therapies. However, the majority of studies have used skin
      fibroblasts to generate induced pluripotent stem cells (iPSCs) that typically
      require the enforced expression of several transcription factors, thereby posing
      a mutagenesis risk by the insertion of viral transgenes. To reduce this risk,
      iPSCs have been generated with OCT4 and KLF4 from human neural stem cells that
      endogenously express the remaining reprogramming factors. However, human neural
      stem cells are rare and difficult to obtain. Here, we show that iPSCs can be
      generated from human amniotic fluid cells (hAFCs) with two transcription factors:
      OCT4 and KLF4. Furthermore, iPSCs can be readily derived from hAFCs in a feeder
      free conditions, thereby eliminating the potential variability caused by using
      feeder cells. Our results indicate that hAFCs represent an accessible source of
      cells that can be reprogrammed into pluripotent stem cells with two Yamanaka
      factors. Therefore, hAFCs may become a preferred cell type in the future for safe
      reprogramming without any exogenous genetic material.

PMID- 23138119
TI  - Expression of endometrial immune-related genes possibly functioning during early
      pregnancy in the mare.
AB  - Despite enormous efforts, biochemical and molecular mechanisms associated with
      equine reproduction, particularly processes of pregnancy establishment, have not
      been well characterized. Previously, PCR-selected suppression subtraction
      hybridization analysis was executed to identify unique molecules functioning in
      the equine endometrium during periods of pregnancy establishment, and granzyme B
      (GZMB) cDNA was found in the pregnant endometrial cDNA library. Because GZMB is
      produced from natural killer (NK) cells, endometrial expression of GZMB and
      immune-related transcripts were characterized in this study. The level of GZMB
      mRNA is higher in the pregnant endometrium than in non-pregnant ones. This
      expression was also confirmed through Western blot and immunohistochemical
      analyses. IL-2 mRNA declined as pregnancy progressed, while IL-15, IFNG and TGFB1
      transcripts increased on day 19 and/or 25. Analyses of IL-4 and IL-12 mRNAs
      demonstrated the increase in these transcripts as pregnancy progressed. Increase
      in CCR5 and CCR4 mRNAs indicated that both Th1 and Th2 cells coexisted in the day
      25 pregnant endometrium. Taken together, the endometrial expression of immune
      related transcripts suggests that immunological responses are present even before
      the trophectoderm actually attaches to the uterine epithelial cells.

PMID- 23138120
TI  - Response to a long-term high-fat diet in the signature of genes involved in lipid
      metabolism in ApoE(-/-) mice.
AB  - High-fat diet (HFD)-induced lipid metabolism disorders are a critical feature of
      diet-induced insulin resistance (IR); however, the mechanisms underlying the
      tissue-specific effects of HFDs on the signature of genes involved in lipid
      metabolism have not been fully investigated. Glucose homeostasis and insulin
      sensitivity were monitored in chow-fed and HFD-fed ApoE mice using the
      hyperinsulinemic-euglycemic clamp technique. The signatures of genes involved in
      lipid metabolism were measured in the liver and adipose tissues by quantitative
      real-time polymerase chain reaction and Western blot analysis. Long-term HFD (for
      16 weeks) resulted in marked abnormalities in glucose and lipid metabolism and
      induced IR in ApoE mice. Long-term HFD also markedly upregulated the messenger
      RNA (mRNA) expression of insulin-induced gene-2, sterol regulatory element
      binding protein cleavage-activating protein and sterol regulatory element-binding
      protein-1 in the liver and/or adipose tissues, in parallel with an elevated
      insulin-induced gene-2 protein in the liver. However, HFD markedly downregulated
      the mRNA expression of sterol regulatory element-binding protein-2, 3-hydroxy-3
      methylglutaryl coenzyme A reductase and low-density lipoprotein receptor in the
      liver. Interestingly, long-term HFD markedly decreased adipose triglyceride
      lipase and peroxisome proliferator-activated receptor-gamma mRNA, and adipose
      triglyceride lipase protein contents in the liver and/or adipose tissues. These
      findings provide a framework to understand the mechanisms by which long-term HFD
      regulates the gene signatures involved in lipid metabolism in the pathogenesis of
      diet-induced IR.

PMID- 23138121
TI  - A case of pyodermatitis-pyostomatitis vegetans.
AB  - Pyodermatitis-pyostomatitis vegetans (PD-PSV) is a rare disorder characterized by
      mucocutaneous involvement and associated with inflammatory bowel disease. A 42
      year-old woman with ulcerative colitis who manifested verrucous and pyogenic
      lesions on her scalp, neck, axillae, inguinal areas, umbilicus, trunk and oral
      cavity for about 11 months is described. She also experienced general fatigue and
      swelling in her lower extremities. Histology revealed eosinophilic inflammation
      with microabscesses and pseudoepitheliomatous hyperplasia, but she was negative
      on direct immunofluorescence for IgA, IgG and C3. She was diagnosed with PD-PSV
      and treated with infusions of 20% human albumin (100 mL) for 5 days, followed by
      methylprednisolone (40 mg/d), with remission of lesions observed after 1 month.
      The differential diagnosis of PD-PSV and pemphigus vegetans is discussed.

PMID- 23138122
TI  - An unusual intra-abdominal calcification in a plain film.

PMID- 23138123
TI  - Half-and-half nail.

PMID- 23138124
TI  - Psychiatric disorder does not preclude adequate continuous positive airway
      pressure titration.
AB  - Obstructive sleep apnea (OSA) is a highly prevalent disorder associated with
      significant morbidity and multiple complications. A large proportion of patients
      with OSA also have a coexisting primary psychiatric disorder. The effect of
      psychiatric disorders on the ability to tolerate continuous positive airway
      pressure (CPAP) titration is not known. In this study, whether the presence of
      psychiatric disorders precludes the patients' ability to tolerate CPAP titration
      for OSA was investigated. A retrospective chart review on a sample of 284
      patients who underwent sleep studies in a single-center, university-based
      Veterans Affairs hospital was performed. A total of 143 patients with OSA who
      underwent titration of CPAP therapy were identified. The prevalence of
      psychiatric disorders between patients who tolerated titration and those who did
      not tolerate it was compared using the chi2 test. The percentages of patients
      with psychiatric disorders who tolerated and did not tolerate CPAP were 33.6% and
      33.3%, respectively. No statistically significant difference between the 2 groups
      (chi2 = 0.051 with 1 degree of freedom; P = 0.82) was found. The predominantly
      male patient population, exclusion of mild OSA, lack of data about the level of
      control of the psychiatric symptoms and the sleep technicians not being blinded
      to the patients' psychiatric diagnoses were some of the limitations of this
      study. No significant difference existed in the prevalence of psychiatric
      disorders between patients intolerant to CPAP titration and those who tolerated
      CPAP for OSA.

PMID- 23138125
TI  - Budd-Chiari syndrome induced by stage IV rectal carcinoid.
AB  - Budd-Chiari syndrome (BCS) is defined as an obstruction of the hepatic venous
      outflow anywhere from the small hepatic veins to the suprahepatic inferior vena
      cava. In this study, a rare case of BCS induced by a metastatic rectal carcinoid
      is presented. A 57-year-old African American woman with stage IV rectal carcinoid
      presented with right upper quadrant pain, associated with decreased appetite and
      weight loss >13 kg over 2 months. Computed tomography scan with contrast
      enhancement revealed filling defects in the left and middle hepatic veins
      extending into the suprahepatic inferior vena cava to the junction of the right
      atrium, suggesting BCS. Thrombophilia workup was negative, and no signs of liver
      cirrhosis or portal hypertension were found. A hepatitis profile workup yielded
      negative results. This is the first reported case of BCS that is associated with
      a metastatic rectal carcinoid. More research is needed to identify the mechanism
      leading to thrombogenesis in carcinoid tumors.

PMID- 23138126
TI  - Hypopituitarism and sphenoid surgery.
AB  - A middle-aged white man underwent sphenoid and ethmoid surgery for rhinitis with
      polyposis. Within days, he developed severe fatigue, myalgias and arthralgias.
      Initial testing demonstrated central hypogonadism, followed by a low normal
      insulin-like growth factor-1 and an abnormal L-dopamine growth hormone
      stimulation test result. As years past, the patient would have such recurrent
      symptoms when ill with the addition of nausea and vomiting. Testing, 7 years
      after his initial surgery, confirmed inappropriate thyroid and cortisol
      responses. His clinical symptoms have resolved with appropriate medical therapy.
      A review of the literature demonstrated no descriptions of hypopituitarism from
      sphenoid surgery.

PMID- 23138127
TI  - Translational educational research: a necessity for effective health-care
      improvement.
AB  - Medical education research contributes to translational science (TS) when its
      outcomes not only impact educational settings, but also downstream results,
      including better patient-care practices and improved patient outcomes. Simulation
      based medical education (SBME) has demonstrated its role in achieving such distal
      results. Effective TS also encompasses implementation science, the science of
      health-care delivery. Educational, clinical, quality, and safety goals can only
      be achieved by thematic, sustained, and cumulative research programs, not
      isolated studies. Components of an SBME TS research program include motivated
      learners, curriculum grounded in evidence-based learning theory, educational
      resources, evaluation of downstream results, a productive research team, rigorous
      research methods, research resources, and health-care system acceptance and
      implementation. National research priorities are served from translational
      educational research. National funding priorities should endorse the contribution
      and value of translational education research.

PMID- 23138128
TI  - Hydrodynamic-based delivery of PTP1B shRNA reduces plasma glucose levels in
      diabetic mice.
AB  - Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of insulin
      signaling which is overexpressed in the liver of diabetic animals. The aims of
      this study were to generate liver-specific PTP1B knockout mice using a PTP1B
      short hairpin RNA (shRNA) plasmid and to investigate the effect of PTP1B
      inhibition on plasma glucose levels in streptozotocin-induced diabetic mice. We
      first validated the hydrodynamic tail vein injection in mice using a vector
      carrying the luciferase gene. Expression of the PTP1B gene was quantified by real
      time PCR. The level of phosphorylated Akt was examined by western blot analysis.
      The injection of the plasmid containing firefly luciferase revealed that the
      highest transfer of the vector into the liver was obtained 24 h after the
      injection of 20 ug plasmid. The injection of PTP1B-shRNA, but not the scrambled
      shRNA plasmid, resulted in a reduction in PTP1B expression levels by up to 84% in
      the liver of the diabetic mice. Plasma glucose levels following the injection of
      PTP1B-shRNA remained significantly lower in the diabetic mice for 5 days. In
      addition, mice receiving PTP1B-shRNA in the basal and insulin-stimulated states
      had higher levels of Akt phosphorylation in the liver cells compared with mice
      that were injected with the scrambled sequence (35 and 60%, respectively;
      p<0.01). Furthermore, PTP1B overexpression was observed in the muscle, liver,
      adipose, heart and kidney tissues of the diabetic mice. The data from this study
      demonstrate that PTP1B inhibition may be a promising approach for lowering plasma
      glucose levels in diabetic patients. However, further studies using non-viral
      carriers are required to deliver the plasmid safely into the liver. 

PMID- 23138130
TI  - Genomics and health care disparities: the role of statistical discrimination.

PMID- 23138131
TI  - Satisfaction of health care professionals managing patients with inflammatory
      bowel disease.
AB  - BACKGROUND AND AIMS: The aim of the present study was to analyze the satisfaction
      of health care professionals who attend patients with inflammatory bowel disease
      (IBD) and to determine the variables more related with
      satisfaction/dissatisfaction. METHODS: Cross-sectional, self-administered written
      15-item questionnaire was evaluated using a Likert scale, completed by Spanish
      gastroenterologists and nurse practitioners specialized in IBD patient care.
      RESULTS: A total of 202 surveys, 133 physicians (65.8%) and 69 nurses (34.2%)
      were conducted. Global scoring of satisfaction was 54.0 for physicians and 64.2
      for nurses (p<0.001). In both groups the highest scores were achieved in those
      items related to their professional careers and management of personal and
      professional lives as well as those that refer to their interdisciplinary
      relationship with other medical units, management of patients within the hospital
      setting and finally communication with the patient. The items that attained the
      lowest score included those related to the length and staff available for the
      medical consult, work environment and the balance among health care provider
      needs for contribution, recognition and fulfillment. With regard to the variables
      involved with satisfaction, the results show that those physicians that only took
      care of IBD patients achieved a higher degree of satisfaction. This could be
      related with the fulfillment of their own professional expectations. CONCLUSIONS:
      The level of satisfaction of health care professionals that take care of IBD
      patients is low and may impact on patient care. Therefore, new strategies to
      increase the degree of satisfaction of IBD health care providers should be
      implemented.

PMID- 23138132
TI  - Prevalence of overweight and obesity in patients with Crohn's disease in Western
      countries and Japan.

PMID- 23138133
TI  - NOTCH1 and SF3B1 mutations can be added to the hierarchical prognostic
      classification in chronic lymphocytic leukemia.

PMID- 23138134
TI  - The impact of close surgical margins after radical hysterectomy for early-stage
      cervical cancer.
AB  - OBJECTIVE: While it is known that positive surgical margins increase the risk of
      cervical cancer recurrence, little is known about the effect of close surgical
      margins (CSM). Therefore, we set out to determine the impact of margin status on
      recurrence and survival in patients with early-stage cervical cancer. METHODS: A
      retrospective review was conducted of patients undergoing radical hysterectomy
      from 2000 to 2010 with Stage IA2-IIA cervical cancer. CSM were defined as <=5mm;
      association with other clinicopathologic factors as well as recurrence and
      survival was evaluated. RESULTS: Of the 119 patients, 75 (63%) with CSM had a
      recurrence rate of 24% compared to 9% without CSM. Though not independently
      associated with recurrence, CSM were significantly associated with positive lymph
      nodes (44% vs. 18%), positive parametria (33.3% vs. 2.3%), larger tumors (3.5 vs.
      2.5cm), greater depth of stromal invasion (DOI) (84% vs. 33%), and lymphovascular
      space invasion (LVSI) (61.3% vs. 34.1%). We failed to find an association between
      adjuvant therapy and recurrence in those with CSM. Exploratory analysis revealed
      that a surgical margin of <=2mm was significantly associated with an increased
      risk of overall recurrence (36% vs. 9%, p=0.009) as well as loco-regional
      recurrence (22% vs. 4%, p=0.0034). CONCLUSIONS: Surgical margins of <=5mm on
      radical hysterectomy specimens are often associated with other high or
      intermediate risk factors for recurrence. While not a proven independent risk
      factor, the distance to surgical margin may warrant further investigation as an
      intermediate risk factor along with tumor size, DOI and LVSI.

PMID- 23138135
TI  - Correlation of tumor size with other prognostic factors in uterine serous
      carcinoma: a large multi-institutional study.
AB  - OBJECTIVE: Uterine serous carcinoma (USC) constitutes 10% of uterine cancers but
      ~40% of deaths. Tumor size is a known prognostic factor in other solid tumors. In
      endometriod cancers it is one element used to identify the need for complete
      staging, while its significance in USC is debated. Therefore tumor size was
      examined as an independent prognostic factor. METHODS: Clinical and pathologic
      variables were recorded for 236 institutional patients, and those patients in the
      SEER database with USC. Chi-square and Fisher exact t-tests were utilized and
      survival data generated via Kaplan-Meier method; multivariate analysis was
      performed via cox-regression. RESULTS: The patients' mean age was 67.2 years
      (range 40-91). Survival ranged from 0 to 184 months (mean 42.8). We used a tumor
      size cut-off of 1cm and noted significant associations with myometrial invasion
      (p<0.0001), angiolymphatic invasion (p<0.0001), peritoneal washings (p=0.03),
      stage (p=0.015) and positive lymph nodes (p=0.05). Furthermore, recurrence was
      associated with larger tumors (p=0.03). In multivariate analysis, extra-uterine
      disease was the only factor associated with both recurrence and survival. Review
      of the SEER database noted association of larger tumors with lymph node
      involvement and a significant survival advantage with tumors <1cm in both
      univariate and multivariate analysis. CONCLUSIONS: Treatment options for USC are
      often predicated on the surgical stage and therefore components of the staging
      are vitally important. The 1cm tumor-size cut-off should be studied prospectively
      as a prognostic indicator of survival and recurrence in USC and considered for
      inclusion in USC staging.

PMID- 23138136
TI  - Nanostructured magnesium increases bone cell density.
AB  - Magnesium has attracted some attention in orthopedics due to its biodegradability
      and mechanical properties. Since magnesium is an essential natural mineral for
      bone growth, it can be expected that as a biomaterial, it would support bone
      formation. However, upon degradation in the body, magnesium releases OH(-) which
      results in an alkaline pH that can be detrimental to cell density (for example,
      osteoblasts or bone forming cells). For this reason, modification of magnesium
      may be necessary to compensate for such detrimental effects to cells. This study
      created biologically inspired nanoscale surface features on magnesium by soaking
      magnesium in various concentrations of NaOH (from 1 to 10 N) and for various
      periods of time (from 10 to 30 min). The results provided the first evidence of
      increased roughness, surface energy, and consequently greater osteoblast
      adhesion, after 4 h as well as density up to 7 days on magnesium treated with any
      concentration of NaOH for any length of time compared to untreated controls. For
      these reasons, this study suggests that soaking magnesium in NaOH could be an
      inexpensive, simple and effective manner to promote osteoblast functions for
      numerous orthopedic applications and, thus, should be further studied.

PMID- 23138137
TI  - World Sight Day: Singapore's contribution to alleviating corneal blindness.

PMID- 23138138
TI  - The co-occurrence of diabetes and depression: an example of the worldwide
      epidemic of comorbidity of mental and physical illness.

PMID- 23138139
TI  - Supplementary breast ultrasound screening in Asian women with negative but dense
      mammograms-a pilot study.
AB  - INTRODUCTION: Dense breasts are common in Asian women and they limit the
      sensitivity of mammography. This study evaluates the performance of supplementary
      breast ultrasound screening in Asian women with dense mammograms. MATERIALS AND
      METHODS: The study was approved by the hospital's Institutional Review Board. A
      prospective clinical trial was performed between September 2002 and November
      2004. Asymptomatic Asian women with negative and dense mammograms were offered
      supplementary ultrasound screening for breast cancer. Ultrasound assessment was
      categorised as U1 to U4. U1 and U2 cases were recommended routine interval
      screening mammography. U3 cases were recommended follow-up ultrasound in 6 months
      and routine interval screening mammography and U4 cases were recommended biopsy.
      RESULTS: One hundred and forty-one women with mean age of 45.1 years were
      enrolled into the study. Mean scan time was 13.0 minutes (+/- 5.6 minutes) for
      bilateral vs 11.0 minutes (+/- 1.4 minutes) for unilateral scans. There were 10
      patients and 14 patients in the in the U3 and U4 categories, respectively. Two U4
      category patients were diagnosed with malignancy-a-6 mm ductal carcinoma-in-situ
      and a 13- mm invasive ductal carcinoma. The breast cancer detection rate was
      1.4%. Sensitivity and specifi city were 100% (2/2) and 88.5% (92/104)
      respectively. The positive predictive value was 14.3% (2/14) and the negative
      predictive value was 100% (92/92). CONCLUSION: This pilot study reveals the
      usefulness of supplementary ultrasound screening in detecting early stage
      mammographically and clinically occult breast cancers in Asian women with dense
      breasts. A larger long-term study is, however, needed to assess its feasibility
      and impact on breast cancer prognosis.

PMID- 23138140
TI  - The combined use of heavy and light silicone oil in the treatment of complicated
      retinal detachment with 360o retinal breaks: tamponade effect or filling effect?
AB  - INTRODUCTION: This study aims to report the safety and effi cacy of the combined
      use of 70% Densiron(r)-68 and 30% polydimethysiloxane as a temporary vitreous
      substitute after pars plana vitrectomy (PPV) in selected cases of retinal
      detachment with superior and inferior retinal breaks. MATERIAL AND METHODS: Fifty
      consecutive eyes of 50 patients affected by complicated retinal detachment with
      retinal breaks of the superior and inferior quadrants associated with
      proliferative vitreoretinopathy (PVR) of grade C2 or more, underwent a pars plana
      vitrectomy and a combination internal tamponade with 70% Densiron(r)-68 and 30%
      silicone oil. The main outcome measures were visual acuity, retinal attachment,
      intraocular pressure (IOP) and incidence of complications. RESULTS: The mean best
      corrected visual acuity rose from 1.4 logMAR to 0.7 logMAR (P <0.01). Initial
      retinal reattachment was achieved in 48 (96%) patients. In 15 patients (30%), IOP
      increased over 21 mmHg. The main complications were redetachment at the 3 month
      follow-up in 12/48 cases (25%) and cataract formation in 13/21 phakic eyes (62%).
      CONCLUSION: This combination tamponade comprised lighter and heavier oil
      compounds was well tolerated and effective. It may be a useful tool for the
      treatment of retinal detachment complicated with breaks and PVR involving the
      upper and lower quadrants.

PMID- 23138141
TI  - The health-related quality of life of junior doctors.
AB  - INTRODUCTION: It is reported that junior doctors experience a large amount of
      work related stress and fatigue which has detrimental effects on their well-being
      and patient safety. We seek to determine the health-related quality of life (HR
      QoL) of junior doctors using the Short Form 36 Health Survey (SF-36) and compare
      their HR-QoL with that of populations of norms and senior doctors. MATERIALS AND
      METHODS: The SF-36v2 (Singapore version) was self-administered to a convenience
      sample of 213 doctors from a large tertiary teaching hospital. Junior doctors
      were defined as those less than 30 years of age (48%). Adjusted normative values
      were derived from the SF-36 Norms for the Singapore General Population Calculator
      for all 8 scales. The mean score differences between junior doctors and their
      adjusted normative values as well as that for senior doctors were computed and
      contrasted. RESULTS: One hundred and eighty-fi ve doctors fully responded. Their
      mean age was 33.6 years (SD 8.1). Also, 45% were female and 88% were Chinese.
      Junior doctors had lower scores than senior doctors in all scales except Physical
      Functioning. After adjustment for gender and race, junior doctors had
      statistically significant lower Mental Health scores than senior doctors (P =
      0.01). Compared with the normative population, junior doctors scored lower in all
      domains except for Physical Functioning. For Vitality, the difference is - 14.9.
      CONCLUSION: Junior doctors have poorer mental health scores compared to senior
      doctors. Also, the lower vitality scores suggest that junior doctors are more
      likely to be fatigued than their normative population. More studies and efforts
      will be needed to identify factors that affect the quality of life in junior
      doctors and to evaluate the most appropriate measures to improve the efficiency
      of their work.

PMID- 23138142
TI  - Early outcome following emergency gastrectomy.
AB  - INTRODUCTION: Emergency gastrectomy has been shown to be associated with poor
      morbidity and mortality rates. The aims of this study were to review the outcomes
      of emergency gastrectomy in our institution and to determine any factors that
      were associated with worse perioperative outcomes. MATERIALS AND METHODS: A
      retrospective review of all patients who underwent emergency gastrectomy for
      various indications from October 2003 to April 2009 was performed. All the
      complications were graded according to the classification proposed by Clavien and
      group. RESULTS: Eighty-fi ve patients, median age 70 (range, 27 to 90 years),
      underwent emergency gastrectomy. The indications for the surgery included
      perforation, bleeding and obstruction in 45 (52.9%), 32 (37.6%) and 8 (9.4%)
      patients, respectively. The majority of the patients (n = 46, 54.1%) had an
      American Society of Anesthesiologists (ASA) score of 3. Partial or subtotal, and
      total gastrectomy were performed in 75 (88.2%) and 10 (11.8%) patients,
      respectively. Malignancy was the underlying pathology in 33 (38.8%) patients. The
      perioperative mortality rate was 21.2% (n = 18) with another 27 (31.8%) patients
      having severe complications. Twelve (14.1%) patients had a duodenal stump leak.
      The independent factors predicting worse perioperative complications included
      high ASA score and in perforation cases. Other factors such as malignancy, age
      and extent of surgery were not signifi cantly related. The presence of a duodenal
      stump leak was the only independent factor predicting mortality. CONCLUSION:
      Emergency gastrectomy is associated with dismal morbidity and mortality rates.
      Patients with high ASA scores and perforations fared worse, and duodenal stump
      leak increases the risk of mortality.

PMID- 23138143
TI  - Prevalence of metabolic syndrome among patients with schizophrenia in Singapore.
AB  - INTRODUCTION: Schizophrenia has been associated with an increased risk of
      cardiometabolic morbidity and mortality. Metabolic syndrome (MetS), a reliable
      predictor of cardiovascular-related morbidity and mortality, has also been shown
      to be more prevalent in patients with schizophrenia. In this study, we
      investigated the prevalence of MetS in a sample of patients with schizophrenia in
      Singapore, and the potential risk factors associated with it. MATERIALS &
      METHODS: One hundred patients with schizophrenia and 300 community controls were
      recruited. All subjects provided a fasted sample of venous blood to measure high
      density lipoprotein cholesterol (HDL-C), triglycerides and glucose levels.
      Weight, height and waist circumference were measured. Presence of MetS was
      assessed according to the American Heart Association and the National Heart, Lung
      and Blood Institute (AHA/NHLBI) guidelines. RESULTS: The prevalence of MetS in
      patients with schizophrenia was 46.0%. The adjusted odds ratio (OR) for MetS
      among patients was 2.79 (CI, 1.50 to 5.20, P = 0.001) when compared with
      controls. Increasing body mass index (BMI) was identifi ed to be signifi cantly
      associated with the prevalence of MetS. CONCLUSION: This study found a high
      prevalence of MetS in Singapore patients with schizophrenia, and that BMI might
      be a risk factor in the development of MetS. This information is clinically
      relevant as BMI is routinely measured in psychiatric practice today, and could be
      used to monitor for development of MetS in schizophrenia.

PMID- 23138144
TI  - Oral aphthosis: management gaps and recent advances.
AB  - INTRODUCTION: Though oral aphthosis is common, it has a significant impact on the
      quality of life in the patients. It is the most common oral ulcerative condition
      encountered in clinical practice. This study describes the characteristics and
      patterns of oral aphthosis seen at a tertiary dermatological centre in Singapore,
      with emphasis in evaluating the management gaps and in identifying underlying
      systemic diseases and nutritional deficiencies. MATERIALS AND METHODS: This is a
      retrospective review of medical records over a 10-year period between June 2000
      and June 2010. Two hundred and thirteen patients were identified using the search
      terms 'oral ulcers', 'aphthous ulcers', 'oral aphthosis', and 'Behcet's disease'.
      Patients with Behcet's disease without oral ulcers and other diagnoses such as
      pemphigus vulgaris, lichen planus and herpes simplex were excluded. The remaining
      patients were evaluated with regard to demographic characteristics,
      characteristics of oral ulcers, associated connective tissue disorders and
      nutritional deficiencies, diagnostic tests results, treatment response as well as
      follow-up duration. RESULTS: One hundred and seventy-fi ve patients were included
      in this study. One hundred and one patients had recurrent oral aphthosis, with 77
      having simple aphthosis and 24 having complex aphthosis. Fourteen patients (8%)
      fulfilled the International Study Criteria (ISG) for Behcet's disease, of which,
      85.71% had complex aphthosis. The therapeutic ladder for such patients ranged
      from topical steroids and colchicine through to oral corticosteroids and/or
      dapsone therapy. CONCLUSION: Recurrent oral aphthosis is a niche condition in
      which dermatologists are well-poised to manage. This study demonstrates that a
      more definitive management and therapeutic algorithm for oral aphthosis are
      needed for better management patients in the future. In particular, complex
      aphthosis needs to be monitored for progression onto Behcet's disease.

PMID- 23138145
TI  - World mental health day.

PMID- 23138146
TI  - Primary breast osteosarcoma: dynamic contrast-enhanced magnetic resonance
      imaging, proton spectroscopy and diffusion weighted imaging findings.

PMID- 23138147
TI  - Multimodality imaging features of rectal schwannoma.

PMID- 23138148
TI  - The effects of classic altitude training on hemoglobin mass in swimmers.
AB  - Aim of the study was to determine the influence of classic altitude training on
      hemoglobin mass (Hb-mass) in elite swimmers under the following aspects: (1)
      normal oscillation of Hb-mass at sea level; (2) time course of adaptation and de
      adaptation; (3) sex influences; (4) influences of illness and injury; (5)
      interaction of Hb-mass and competition performance. Hb-mass of 45 top swimmers
      (male 24; female 21) was repeatedly measured (~6 times) over the course of 2
      years using the optimized CO-rebreathing method. Twenty-five athletes trained
      between one and three times for 3-4 weeks at altitude training camps (ATCs) at
      2,320 m (3 ATCs) and 1,360 m (1 ATC). Performance was determined by analyzing 726
      competitions according to the German point system. The variation of Hb-mass
      without hypoxic influence was 3.0 % (m) and 2.7 % (f). At altitude, Hb-mass
      increased by 7.2 +/- 3.3 % (p < 0.001; 2,320 m) and by 3.8 +/- 3.4 % (p < 0.05;
      1,360 m). The response at 2,320 m was not sex-related, and no increase was found
      in ill and injured athletes (n = 8). Hb-mass was found increased on day 13 and
      was still elevated 24 days after return (4.0 +/- 2.7 %, p < 0.05). Hb-mass had
      only a small positive effect on swimming performance; an increase in performance
      was only observed 25-35 days after return from altitude. In conclusion, the
      altitude (2,320 m) effect on Hb-mass is still present 3 weeks after return, it
      decisively depends on the health status, but is not influenced by sex. In healthy
      subjects it exceeds by far the oscillation occurring at sea level. After return
      from altitude performance increases after a delay of 3 weeks.

PMID- 23138149
TI  - The impact of the site of blood sampling on pharmacokinetic parameters following
      sublingual dosing to dogs.
AB  - INTRODUCTION: Drugs are most commonly administered orally, but some potential
      drug candidates are not suited for oral administration due to poor absorption,
      high first pass metabolism or gastrointestinal side effects. The interest for
      transmucosal dosing for systemic drug delivery is increasing, e.g. buccal,
      sublingual and nasal routes. The evaluation of the systemic plasma concentration
      and the derivation of the pharmacokinetic parameters of candidate compounds in
      preclinical studies are essential for drug development. The effect of site of
      blood sampling on the measured drug concentration, in both animals and humans, is
      to some extent known but it is not always taken into consideration in the design
      of pharmacological and toxicological studies. METHODS: Blood samples were
      collected both from leg and jugular veins from beagle dogs following a single
      sublingual dosing of Compound A in order to determine the impact of different
      sites of blood sampling on plasma pharmacokinetics. Plasma was prepared by
      centrifugation and plasma concentrations of Compound A were determined by protein
      precipitation and liquid chromatography followed by mass spectrometric detection.
      The pharmacokinetic parameters were calculated by non-compartment methods.
      RESULTS: Sampling from the jugular vein resulted in higher and more variable
      exposure during the absorption phase compared to sampling from a leg vein. The
      plasma exposure in the jugular vein, in terms of C(max), was 4-fold compared to
      that in the leg vein and an approximately 2-fold bioavailability was observed.
      DISCUSSION: The aim of this investigation was to determine the impact of the
      different sites of blood sampling on assessing systemic plasma exposure and
      pharmacokinetic parameters for Compound A following sublingual dosing to dogs.
      The results demonstrate the significant impact that the site of blood sampling
      has on PK parameters, and raise concerns of using the jugular vein as a site of
      sampling after sublingual and other transmucosal routes of dosing in the head
      region.

PMID- 23138150
TI  - Screening quality for Ca2+-activated potassium channel in IonWorks Quattro is
      greatly improved by using BAPTA-AM and ionomycin.
AB  - INTRODUCTION: IonWorks automated patch clamp systems are being widely used for
      ion channel drug discovery, but the perforated patch mode of these systems makes
      it difficult to obtain a steady intracellular Ca(2+) concentration ([Ca(2+)](i)).
      This difficulty prevents obtaining high-quality data regarding Ca(2+)-activated
      channels such as BK and SK channels. We examined the methods for stabilizing
      [Ca(2+)](i) in the IonWorks Quattro automated patch clamp system to evaluate BK
      channels. METHODS: Electrophysiological recordings were performed using the
      single-hole or population patch clamp mode of IonWorks Quattro. To increase
      [Ca(2+)](i), ionomycin was used. The variation in the BK current and the effect
      of BK channel modulators were examined in the presence and absence of an
      intracellular Ca(2+) chelator, BAPTA-AM (20MUM). RESULTS: BK current activated by
      step pulses to +100mV in the presence of ionomycin exhibited large variation
      (ranging from 0.086 to 11nA). In individual cells, oscillation of the current
      amplitude was observed when five repetitive pulses were applied at 0.1Hz.
      Approximately 30% of cells exhibited current variation exceeding 20% when the
      variation was calculated using the first and third pulses. However, BAPTA-AM
      treatment before current measurement decreased the number of cells displaying
      large variation (>20%) to 5%. In the presence of BAPTA-AM, the BK channel
      modulators NS1619 and 12,14-dichlorodehydroabietic acid increased the BK current
      at concentrations of 10MUM or more showing clear concentration dependency,
      whereas in its absence, the effect of both compounds was detected only at 30MUM.
      DISCUSSION: The main finding of this study is that the [Ca(2+)](i) variation in
      the basal condition is very large and hinders the accurate evaluation of
      compounds in Ca(2+)-activated ion channels. The application of BAPTA-AM and
      ionomycin greatly improved the precision of BK channel screening, and this method
      should be applicable to other Ca(2+)-activated ion channels such as SK channels.

PMID- 23138152
TI  - Easily accessible, hydrocarbon-soluble, crystalline, anhydrous lanthanide (Nd,
      La, and Y) phosphates.
AB  - Nd, La and Y triphosphates were prepared via the reaction of potassium ionol
      ethyl phosphate with the corresponding lanthanide nitrates or chlorides in water.
      According to the X-ray diffraction data, the recrystallised reaction products
      were dimers. The products did not contain water, were readily soluble in
      hydrocarbon solvents and demonstrated promising catalytic properties in the
      polymerisation of butadiene and DL-dilactide.

PMID- 23138151
TI  - Evaluation of Camellia sinensis catechins as a swine antimicrobial feed additive
      that does not cause antibiotic resistance.
AB  - Antimicrobial growth promoters (AGPs) have been banned and phased out because
      their use has been linked to the emergence and spread of antibiotic-resistant
      pathogens; however, the ban has had a marked impact on livestock production, and
      feed additive alternatives to AGPs are required. We focused on green tea leaves
      as potential alternatives to AGPs because they contain significant amounts of
      polyphenol catechins, which have antivirus and antimicrobial effects. We examined
      cross-resistance between epigallocatechin gallate (EGCG), which is the most
      abundant catechin of green tea leaves, and commercially available antimicrobials
      in clinically problematic antimicrobial-resistant bacteria, and whether bacteria
      have the ability to acquire resistance by consecutive passage in sub-inhibitory
      concentrations of EGCG. EGCG did not display any cross-resistance with reference
      antimicrobials and the bacteria did not acquire EGCG resistance. Further, we
      examined the growth-promoting effects of dried green tea leaves on the breeding
      of a new Japanese breed, Tokyo-X pigs. While the mortality rates of the green tea
      leaf (GTL) and AGP groups were both 11.1% (one in nine piglets), the mortality
      rate was 50% for the control group with an additive-free diet (four in eight
      piglets). The rate of body weight increase in both the GTL and AGP groups was
      approximately the same. The growth-promoting effects of green tea leaves and AGPs
      were similar, and there was no possibility that the antimicrobial properties of
      catechins caused the same problem as AGPs. Thus, it can be concluded that green
      tea leaves are a safe feed additive alternative to AGPs.

PMID- 23138153
TI  - Ancient RNA? RT-PCR of 50-year-old RNA identifies peach latent mosaic viroid.
AB  - The preservation of macromolecules is at best haphazard. Modern techniques have
      improved the detection of ancient DNA and proteins, but there is little
      information on the preservation of RNA. Fifty-year-old dried leaf material
      showing symptoms of peach calico disease was used successfully in RT-PCRs to
      amplify peach latent mosaic viroid (PLMVd) RNA and the mRNA for the large subunit
      of ribulose 1,5-bisphosphate carboxylase (rubisco). These results indicate that
      naked RNA may be preserved, under suitable conditions, for at least 50 years. The
      results are discussed in the context of ancient DNA and proteins and the process
      of fossilization.

PMID- 23138154
TI  - Sequential changes in the non-coding control region sequences of JC
      polyomaviruses from the cerebrospinal fluid of patients with progressive
      multifocal leukoencephalopathy.
AB  - Progressive multifocal leukoencephalopathy (PML) is caused by JC polyomavirus
      (JCV) infection in the brain. JCV isolates from PML patients have variable
      mutations in the non-coding control region (NCCR) of the genome. This study was
      conducted to examine sequential changes in NCCR patterns of JCV isolates obtained
      from the cerebrospinal fluid (CSF) of PML patients. CSF specimens were collected
      from PML patients at different time points, the NCCR sequences were determined,
      and their compositions were assessed by computer-based analysis. In patients
      showing a marked increase in JCV load, the most frequent NCCR sequences in the
      follow-up specimens were different from those in the initial samples. In
      contrast, the dominant NCCRs in the CSF remained unaltered during the follow-up
      of individuals in whom the viral load decreased after therapeutic intervention.
      These data demonstrate that the majority of JCV variants emerge with the
      progression of PML and that these changes are suppressed when the viral load is
      decreased.

PMID- 23138155
TI  - Isolation of a novel herpesvirus from a Pacific white-sided dolphin.
AB  - During establishment of primary cell culture from the kidney of a dead Pacific
      white-sided dolphin (Lagenorhynchus obliquidens), a cytopathic effect was
      observed. Polymerase chain reaction with a set of herpesvirus consensus primers
      yielded a fragment of the expected size. Nucleotide sequencing of the product
      indicated that the isolated virus was closely related to an alphaherpesvirus
      detected in a bottlenose dolphin in the United States, but the sequence identity
      at the protein level was low (86.6 %). Phylogenetic analysis of the encoded
      sequence confirmed that the new isolate belonged to the subfamily
      Alphaherpesvirinae and clustered together with other cetacean alphaherpesviruses.
      The complete gene encoding glycoprotein B (2,757 bp) was amplified from the novel
      isolate; the encoded protein was compared with the corresponding protein of other
      herpesviruses, revealing that this virus belongs to the genus Varicellovirus.
      Taken together, these results suggest that this virus corresponds to a novel
      herpesvirus capable of infecting Pacific white-sided dolphins.

PMID- 23138156
TI  - Self-reported adherence measures: what do they assess and how should we use them?

PMID- 23138157
TI  - Perceptually specific and perceptually non-specific influences on rereading
      benefits for spatially transformed text: evidence from eye movements.
AB  - The present study used eye tracking methodology to examine rereading benefits for
      spatially transformed text. Eye movements were monitored while participants read
      the same target word twice, in two different low-constraint sentence frames. The
      congruency of perceptual processing was manipulated by either applying the same
      type of transformation to the word during the first and second presentations
      (i.e., the congruent condition), or employing two different types of
      transformations across the two presentations of the word (i.e., the incongruent
      condition). Perceptual specificity effects were demonstrated such that fixation
      times for the second presentation of the target word were shorter for the
      congruent condition compared to the incongruent condition. Moreover, we
      demonstrated an additional perceptually non-specific effect such that second
      reading fixation times were shorter for the incongruent condition relative to a
      baseline condition that employed a normal typography (i.e., non-transformed)
      during the first presentation and a transformation during the second
      presentation. Both of these effects (i.e., perceptually specific and perceptually
      non-specific) were similar in magnitude for high and low frequency words, and
      both effects persisted across a 1 week lag between the first and second readings.
      We discuss the present findings in the context of the distinction between
      conscious and unconscious memory, and the distinction between perceptually versus
      conceptually driven processing.

PMID- 23138158
TI  - Structure, energy, vibrational spectrum, and Bader's analysis of pi...H hydrogen
      bonds and H(-delta)...H(+delta) dihydrogen bonds.
AB  - In this paper, the intermolecular structural study asserted by the vibrational
      analysis in the stretch frequencies of hydrogen bonds (pi...H) and dihydrogen
      bonds (H(-delta)...H(+delta)) have definitively been revisited by means of
      calculations carried out by Density Functional Theory (DFT) and topological
      parameters derived from the classic treatise of the Quantum Theory of Atoms in
      Molecules (QTAIM). As a matter of fact the pi...H hydrogen bond is formed between
      the hydrofluoric acid and the C=C bond of the acetylene, but the QTAIM
      calculations revealed a distortion in this interaction due to the formation of
      the ternary complex C(2)H(2)...2(HF). Although the pi bonds of ethylene
      (C(2)H(4)), propylene (C(2)H(3)(CH(3))), and t-butylene (C(2)H(2)(CH(3))(2)) are
      considered proton acceptors, two hydrogen-bond types--pi...H and C...H--can be
      observed. Over and above the analysis of the pi hydrogen bonds, theoretical
      arguments also were used to discuss the red-shifts in the stretch frequencies of
      the binary dihydrogen complexes formed by BeH(2)...HX with X = F, Cl, CN, and
      CCH. Although a vibrational blue-shift in the stretch frequency of the H-C bond
      of HCF(3) due to the formation of the BeH(2)...HCF(3) dihydrogen complex was
      obtained, unmistakable red-shifts were detected in LiH...HCF(3), MgH(2)...HCF(3),
      and NaH...HCF(3). Moreover, the alkali-halogen bonds were identified in relation
      to the formation of the trimolecular systems NaH...2(HCF(3)) and
      NaH...2(HCCl(3)). At last, theoretical calculations and QTAIM molecular
      integrations were used to study a novel class of dihydrogen-bonded complexes
      (mC(2)H(5)(+)...nMgH(2) with m = 1 or 2 and n = 1 or 2) based in the insight that
      MgH(2) can bind with the non-localized hydrogen H(+delta) of the ethyl cation
      (C(2)H(5)(+)). In an overview, QTAIM calculations were applied to evaluate the
      molecular topography, charge density, as well as to interpret the shifted
      frequencies either to red or blue caused by the formation of the hydrogen bonds
      and dihydrogen bonds.

PMID- 23138159
TI  - A "shot heard 'round the world" on cancer drug costs?

PMID- 23138160
TI  - The oncologist's impact on drug choices.

PMID- 23138161
TI  - Lung cancer screening: the last 10 years.

PMID- 23138162
TI  - Successful resection after neoadjuvant therapy in pancreatic adenocarcinoma.
AB  - A 59-year-old woman presented with borderline resectable pancreatic
      adenocarcinoma involving the neck and body of the pancreas. She was treated with
      systemic chemotherapy followed by chemoradiation, with subsequent downstaging of
      the tumor by imaging. Subsequent resection had negative margins and negative
      lymph nodes with only microscopic disease present in the tumor specimen.
      Neoadjuvant therapy is controversial but could play a role in borderline
      resectable disease by allowing for higher chance of negative margins at surgery
      and increasing the chance for cure in these patients. Microscopic disease at time
      of resection is rare.

PMID- 23138163
TI  - Ovarian cancer, version 3.2012.
AB  - These NCCN Guidelines Insights focus on the major updates for the 2012 NCCN
      Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Ovarian Cancer by
      describing how and why the new recommendations were made. The 6 update topics
      were selected based on recent important updates in the guidelines and on debate
      among panel members about recent clinical trials, and include: 1) screening, 2)
      diagnostic tests for assessing pelvic masses, 3) primary treatment using
      neoadjuvant chemotherapy, 4) primary adjuvant treatment using bevacizumab in
      combination with chemotherapy, 5) therapy for recurrent disease, and 6)
      management of drug/hypersensitivity reactions. These NCCN Guidelines Insights
      also discuss why some recommendations were not made (eg, panel members did not
      feel the new data warranted changing the guideline). See "Updates" in the NCCN
      Guidelines for Ovarian Cancer for a complete list of all the recent revisions.

PMID- 23138164
TI  - Update on emerging technologies in breast imaging.
AB  - Despite mammography's proven efficacy, there continues to be interest in newer
      technologies in breast cancer detection and expanded use of established
      technologies, especially in women with dense breast tissue and those at high
      risk. This article reflects on the development in the last ten years of some of
      these modalities and their current use.

PMID- 23138165
TI  - Point: Treating stage II colon cancer: the quest for personalized adjuvant care.
AB  - The development of treatment decision strategies to guide the use of adjuvant
      chemotherapy in patients with stage II colon cancer continues to challenge many
      oncologists. Clearly, recurrence risk and prognosis for patients with stage II
      colon cancer can be variable, with subsets of patients with stage II disease at
      potentially higher risk than some with stage III. Adjuvant chemotherapy seems to
      produce a consistent relative risk reduction for recurrence across studies. Using
      clinical calculators to predict individual recurrence risk based on
      histopathologic and patient data allows this relative risk reduction to be
      translated into absolute benefit to the patient. In addition, gene expression
      assays in combination with these histopathologic data may further improve the
      accuracy of recurrence risk calculations and allow more accurate absolute benefit
      estimations. This absolute benefit should be discussed with the patient, taking
      into account the risk of morbidity from chemotherapy and individual preferences
      to arrive at a shared medical decision regarding adjuvant chemotherapy.

PMID- 23138166
TI  - Counterpoint: Adjuvant therapy in stage II colon cancer: pain not justified by
      the gain.
AB  - No definitive evidence shows benefit from adjuvant therapy for stage II colon
      cancer, and its role remains controversial. Although a trend toward improved
      disease-free survival (DFS) has been reported in subgroup analyses from clinical
      trials that included patients with stage II disease, time trends for recurrences
      of stage II disease indicate that DFS is not a reliable surrogate for overall
      survival (OS). Several clinical trials have been conducted to answer the question
      of whether adjuvant therapy benefits patients with stage II disease, but none
      have been adequately powered to detect what would be a small OS benefit. Features
      that are currently used to assign high risk for recurrence (tumor perforation,
      lymphovascular invasion, <12 lymph nodes analyzed, and poorly differentiated
      histology) may or may not be associated with clinical outcome, and they are not
      predictive of treatment benefit. Risks of adjuvant therapy are non-negligible and
      must be weighed against a large number of patients needed to be treated to
      realize benefit. Future research should aim to answer the questions of whether
      microsatellite instability, nodal sampling, molecular markers, and genetic
      signatures are useful tools to guide decision-making. Given what is now known,
      the viewpoint is that the aggregate data do not support adjuvant therapy for
      patients with normal-risk stage II colon cancer.

PMID- 23138167
TI  - A randomized phase II study of cetuximab every 2 weeks at either 500 or 750 mg/m2
      for patients with recurrent or metastatic head and neck squamous cell cancer.
AB  - Cetuximab is typically administered on a weekly schedule for patients with
      recurrent or metastatic head and neck squamous cell cancer (HNSCC). This study
      explores cetuximab administered every 2 weeks (q2w). In this multicenter
      randomized prospective phase II study, eligible patients (<=2 prior cytotoxic
      chemotherapy regimens for recurrent or metastatic disease; ECOG performance
      status <=2) were randomized to receive cetuximab q2w at 500 mg/m(2) (Group A) or
      750 mg/m(2) (Group B). The primary end point was response rate (RECIST 1.0).
      Sixty-one patients were enrolled: 35 in Group A and 26 in Group B, which was
      closed early for lack of efficacy. Confirmed partial response rates were 11% for
      Group A (4/35) and 8% for Group B (2/26) according to intention to treat
      analysis. Partial responses occurred only among patients whose primary tumors
      were in the oral cavity or larynx. Median progression-free survival (PFS) and
      median overall survival (OS) were similar for both groups (PFS, 2.2 and 2.0
      months; OS, 7.0 and 9.4 months; Groups A and B, respectively). The most common
      cetuximab-related adverse events (all grades) among treated subjects included
      rash, fatigue, and hypomagnesemia. Cetuximab, 500 mg/m(2), q2w achieves similar
      efficacy as conventional dosing for patients with recurrent or metastatic HNSCC.
      Escalating the dose to 750 mg/m(2) q2w offers no obvious therapeutic advantage.

PMID- 23138168
TI  - New agents in metastatic prostate cancer.
AB  - Discoveries of molecular mechanisms and therapeutic targets in metastatic
      castration-resistant prostate cancer (CRPC) have led to significant advancements
      in the development of effective agents in this setting, with diverse mechanisms
      of action. Within the past 2 years, 5 agents have been approved for the treatment
      of patients with metastatic CRPC (cabazitaxel, abiraterone, sipuleucel-T,
      denosumab, and enzalutamide), and another (Alpharadin) has shown overall survival
      benefit in a phase III trial. This article summarizes the phase III data showing
      clinical benefit from these agents, highlights other promising therapies in phase
      III studies as single agents (PROSTVAC-VF, ipilimumab, cabozantinib), discusses
      important unanswered questions regarding these therapies, and provides a schema
      for their use based on current regulatory approval and how this is likely to
      evolve as data from ongoing studies are reported. Although curative interventions
      in metastatic CRPC still do not exist, the hope is that optimization of
      therapeutic strategies can reduce the morbidity and mortality associated with
      this disease.

PMID- 23138169
TI  - Prevention and treatment of cancer-related infections.
AB  - Patients with cancer are at increased risk for developing infectious
      complications during the course of their disease and treatment. The following
      sections of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines)
      for Prevention and Treatment of Cancer-Related Infections provide an overview of
      the risk factors for infectious complications, recommendations for infectious
      risk categorization, and strategies for prevention of infections in high-risk
      patient populations with cancer. Individualized risk evaluation for infections
      and incorporation of preventative measures are essential components of the
      overall spectrum of cancer care, and may contribute to optimizing treatment
      outcomes for patients.

PMID- 23138170
TI  - Current issues in vaccines for adult patients with hematologic malignancies.
AB  - Vaccination is an important strategy for preventing infections in patients with
      hematologic malignancies. Hematopoietic cell transplant (HCT) recipients have
      diminished immunity against vaccine-preventable diseases after transplantation.
      Optimal timing for initiating immunization in the context of hematologic
      malignancies and after HCT, however, is not well defined, and data on the
      magnitude and duration of immune response to vaccines in this population are
      lacking. Factors such as degree of immunosuppression, administration of
      monoclonal antibodies, time after HCT, and presence or absence of chronic graft
      versus-host disease may influence the immune response to vaccines and may pose
      safety concerns for certain vaccines, such as live-attenuated immunogens.
      Patients who received certain monoclonal antibodies (eg, rituximab, alemtuzumab)
      less than 6 months before vaccination have poorer immune responses to vaccines.
      New advancements in vaccine development are warranted to improve safety and
      immunogenicity of vaccination in immunocompromised patients.

PMID- 23138171
TI  - BRAF mutations in colorectal cancer: clinical relevance and role in targeted
      therapy.

PMID- 23138173
TI  - Inhalation of carbon monoxide following resuscitation ameliorates hemorrhagic
      shock-induced lung injury.
AB  - Even after successful resuscitation, hemorrhagic shock frequently causes
      pulmonary inflammation that induces acute lung injury (ALI). We previously
      demonstrated that when CO is inhaled at a low concentration both prior to and
      following hemorrhagic shock and resuscitation (HSR) it ameliorates HSR-induced
      ALI in rats due to its anti-inflammatory effects. In the present study, we
      administered CO to the same model of ALI only after resuscitation and examined
      whether it exerted a therapeutic effect without adverse events on HSR-induced
      ALI, since treatment of animals with CO prior to HSR did not prevent lung injury.
      HSR were induced by bleeding animals to achieve a mean arterial pressure of 30
      mmHg for 1 h followed by resuscitation with the removed blood. HSR resulted in
      the upregulation of inflammatory gene expression and increased the rate of
      apoptotic cell death in the lungs. This was determined from an observed increase
      in the number of cells positive for transferase-mediated dUTP-fluorescein
      isothiocyanate (FITC), nick-end labeling staining and activated caspase-3. HSR
      also resulted in prominent histopathological damage, including congestion, edema,
      cellular infiltration and hemorrhage. By contrast, CO inhalation for 3 h
      following resuscitation significantly ameliorated these inflammatory events,
      demonstrated by reduced histological damage, inflammatory mediators and apoptotic
      cell death. The protective effects of CO against lung injury were notably
      associated with an increase in the protein expression level of peroxisome
      proliferator-activated receptor (PPAR)-gamma, an anti-inflammatory
      transcriptional regulator in the lung. Moreover, CO inhalation did not affect the
      hemodynamic status or tissue oxygenation during HSR. These findings suggest that
      inhalation of CO at a low concentration exerts a potent therapeutic effect
      against HSR-induced ALI and attenuates the inflammatory cascade by increasing
      PPAR-gamma protein expression. 

PMID- 23138174
TI  - Comparative analysis of the Alzheimer questionnaire (AQ) with the CDR sum of
      boxes, MoCA, and MMSE.
AB  - The Alzheimer Questionnaire (AQ) has been established as a valid and accurate
      informant-based screening questionnaire for Alzheimer disease and amnestic mild
      cognitive impairment. Although the AQ's validity and diagnostic accuracy has been
      established, its performance in comparison with other instruments has not. Thirty
      nine amnestic mild cognitive impairment cases and 34 Alzheimer disease cases were
      matched on the basis of age, education, and sex to 73 cognitively normal
      individuals. The sample had a mean age of 82.54+/-7.77 years and a mean education
      level of 14.61+/-2.61 years. The diagnostic accuracy of the CDR Sum of Boxes,
      Mini Mental State Exam (MMSE), and Montreal Cognitive Assessment (MoCA) were
      compared with the AQ. The AQ correlated strongly with the CDR Sum of Boxes
      (r=0.79) and demonstrated similar diagnostic accuracy with the MoCA and MMSE.
      These results suggest that the AQ is comparable with other established informant
      based and patient-based measures. 

PMID- 23138175
TI  - The influence of aquariums on weight in individuals with dementia.
AB  - This study assessed whether individuals with dementia who observe aquariums
      increase the amount of food they consume and maintain body weight. The sample
      included 70 residents in dementia units within 3 extended care facilities in 2
      states. The intervention included the introduction of an aquarium into each
      common dining area. A total increase of 196.9 g of daily food intake (25.0%) was
      noted from baseline to the end of the 10-week study. Resident body weight
      increased an average of 2.2 pounds during the study. Eight of 70 residents
      experienced a weight loss ((Equation is included in full-text article.)=1.89
      lbs). People with advanced dementia responded to aquariums in their environment
      documenting that attraction to the natural environment is so innate that it
      survives dementia. 

PMID- 23138176
TI  - Ovarian cancer stem cells: working towards the root of stemness.
AB  - Despite medical advances made over the past decade, ovarian cancer remains one of
      the more lethal gynecologic cancers in the United States. While current
      therapeutic strategies are relatively effective, there is a high incidence of
      recurrent chemoresistant disease. This has been attributed, in part, to a
      regenerative tumor cell sub-population that has acquired stem cell properties
      which allows these cells to escape standard chemotherapeutics and drive recurrent
      disease. To date, a number of laboratories have identified these cancer stem cell
      (CSC) sub-populations in ovarian cancer cell lines, tumors or ascites and the
      collective findings suggest ovarian CSCs are likely to be as heterogeneous as the
      disease itself. Moreover, the multiple ovarian histophenotypes and possible sites
      of disease origin together with the potential for differential hierarchal
      contributions of multiple CSCs populations represent significant challenges to
      the identification, functional characterization and therapeutic targeting of
      ovarian CSC. This review will highlight the markers and methodology currently
      used to identify and isolate these cells. We will discuss some of the underlying
      ovarian CSC biology, the signaling pathways implicated in their survival,
      replication and differentiation and potential therapeutic targeting strategies. 

PMID- 23138177
TI  - Phylogeny of microcystins: evidence of a biogeographical trend?
AB  - Microcystins, the most prevalent cyanotoxins occurring worldwide, were first
      recorded in the species Microcystis aeruginosa. Its production has been reported
      in all continents; thus, we propose a comprehensive phylogenetic study to
      characterize M. aeruginosa microcystin-producing strains and establish whether or
      not the species has an historic biogeography. To accomplish this, we compared
      phylogenetically the nucleotide sequences of three genes of the mcy gene cluster
      (mcyA, mcyD and mcyG) from toxin producing M. aeruginosa strains across all the
      five continents. The obtained results provided valuable insight on the
      biogeography of M. aeruginosa produced microcystins: (i) the Asian strains showed
      to be distinct from the other continental groups indicating a genetically unique
      population and (ii) Asian strains were more related to European and North
      American strains. Moreover, the evidence of positive selection was determined in
      all the three mcy genes indicating that some functionality yet to be determined
      could be under selection for these genes.

PMID- 23138178
TI  - Liquid chromatography-tandem mass spectrometry approach for quantification of
      mucins from sputum using 13C,15N-labeled peptides as internal standards.
AB  - Mucins are of great interest owing to their involvement in physiological and
      pathological processes in the airways. A method that allows accurate
      quantification of such proteins in sputum samples may be helpful for research in
      this field. A liquid chromatographic selected reaction monitoring (SRM) method
      was developed for the quantification of two mucins, MUC5AC and MUC5B, in induced
      sputum samples. Sample preparation for the assay included solubilization,
      reduction, and alkylation prior to tryptic digestion. Solid phase extraction
      using C18 sorbent was used for sample cleanup prior to the liquid chromatography
      tandem mass spectrometry (LC-MS/MS) analysis. A cysteine-containing peptide was
      selected for quantification of MUC5AC protein, whereas a non-cysteine peptide was
      used for the quantification of MUC5B protein. Stable isotope-labeled synthetic
      peptides were used as internal standards, and linear calibration curves were
      constructed in the range of 0.3 to 40 pmol/L. Both mucins could be determined
      with a precision of 6 to 19% and an accuracy of 98 to 114%. The method is
      transferable to robotics and is suitable to be run in a 96-well format.

PMID- 23138179
TI  - A high-throughput screening assay using Krabbe disease patient cells.
AB  - Globoid cell leukodystrophy (GLD) or Krabbe disease is a lysosomal disease caused
      by beta-galactocerebrosidase (GALC) deficiency resulting in a rapidly progressive
      neurodegenerative disorder. Unfortunately, the only available treatment is
      hematopoietic bone marrow transplantation, which prevents its fulminant
      manifestation but without treating further neurological manifestations. Here, we
      describe the development of a cellular high-throughput screening (HTS) assay
      using GLD patient fibroblasts to screen for small molecules that enhance the
      residual mutant GALC enzymatic activity. Small molecules have substantial
      therapeutic potential in GLD because they are more prone to cross the blood-brain
      barrier, reaching the neuronal affected cells. The transformation of primary skin
      fibroblasts with SV40 large T antigen has been shown to maintain the biochemical
      characteristics of the GLD cells and generates sufficient cells for the HTS.
      Using a specific fluorescent substrate, residual GALC activity from an SV40
      transformed GLD patient fibroblast was measurable in high-density microplates.
      The pilot quantitative HTS against a small compound collection showed robust
      statistics. The small molecules that showed active concentration-response curves
      were further studied in primary GLD fibroblasts. This cell-based HTS assay
      demonstrates the feasibility of employing live GLD patient cells to identify
      therapeutic agents that can potentially be used for the treatment of this
      progressive neurodegenerative disease.

PMID- 23138180
TI  - Lymphadenectomy with robotic cystectomy.
AB  - It is now established that an experienced, dedicated robotic surgeon can perform
      a high quality extended template pelvic lymph node dissection at the time of
      robot-assisted radical cystectomy. The evidence for this conclusion can be seen
      in comparing absolute lymph node counts, percent positive lymph nodes, and
      oncologic outcomes from N1 patients. In this report, we outline the endpoints of
      study for this question, and report recent data on efforts to advance robot
      assisted urinary diversion, cost-focused studies, and standardized complication
      reporting. These studies demonstrate maintenance of adequate lymph node
      dissections while advancing the goal of reducing morbidity for patients needing
      radical cystectomy for invasive disease.

PMID- 23138181
TI  - Physicians compliance during maintenance therapy in children with Down syndrome
      and acute lymphoblastic leukemia.
AB  - Children with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) have an
      inferior prognosis compared with non-DS ALL patients. We reviewed methotrexate
      (MTX)/mercaptopurine (6MP) maintenance therapy data for children with DS treated
      according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO)
      ALL92 or the NOPHO ALL2000 protocols between 1992 and 2007. The 5-year event-free
      survival probability (pEFS(5 yr)) for the 66 DS patients was inferior to the 2602
      non-DS patients (0.50 +/- 0.07 vs 0.77 +/- 0.01 (P<0.001)). The 48 DS patients in
      first remission at the beginning of maintenance therapy had pEFS(10 yr) below
      that of the 522 non-DS control patients (pEFS(10 yr): 0.58 (95% confidence
      interval (CI) 0.43-0.77) vs 0.83 (95% CI 0.80-0.86), respectively (P<0.0001)).
      The DS patients received lower median doses of MTX (median: 11.8 vs 15.4
      (P<0.0001)) and 6MP (median: 43.6 vs 59.4 (P<0.0001)). In Cox regression
      analysis, male gender, presence of DS and high median maintenance therapy white
      blood cell levels (mWBC) were associated with increased risk for relapse. DS-ALL
      patients with mWBC above or below 3.5 * 10(9)/l (protocol target) had pEFS(10 yr)
      of 0.31 and 0.72 (P=0.02), and the mWBC hazard ratio for DS-ALL patients was 2.0
      (P<0.0005). We conclude that insufficient treatment intensity during maintenance
      therapy of DS-ALL patients may contribute to their poor prognosis.

PMID- 23138182
TI  - Fas apoptosis inhibitory molecule is upregulated by IGF-1 signaling and modulates
      Akt activation and IRF4 expression in multiple myeloma.
AB  - Multiple myeloma (MM) is an incurable malignancy of terminally differentiated B
      lymphoid cells. Here, we investigate the role of Fas apoptosis inhibitory
      molecule (FAIM) in MM. We demonstrate that insulin-like growth factor 1 (IGF-1)
      treatment upregulated FAIM expression in MM cells in a dose-dependent manner.
      Silencing of FAIM expression attenuates Akt signaling downstream of IGF-1 and
      compromises the viability of MM cells. We further showed that IGF-1 stimulation
      of MM cells leads to enhanced expression of IRF4, a known 'addictive' factor for
      MM. This upregulation of IRF4 expression by IGF-1 treatment of MM cells is
      abrogated when FAIM expression is silenced or Akt activation is inhibited. Thus,
      FAIM modulates IGF-1-induced Akt activation and IRF4 expression and has a role in
      MM cell survival. Consistent with these findings, FAIM expression is shown to be
      higher in plasma cells of symptomatic MM patients compared with normal
      individuals or patients with premalignant conditions. Moreover, a higher level of
      FAIM expression is shown to correlate with poorer survival outcomes of newly
      diagnosed MM patients treated with stem cell transplantation or relapsed MM
      patients treated in clinical trials with Bortezomib. Thus taken together, our
      study reveals a novel, as well as clinically relevant role for FAIM in MM.

PMID- 23138183
TI  - Abrogation of MLL-AF10 and CALM-AF10-mediated transformation through genetic
      inactivation or pharmacological inhibition of the H3K79 methyltransferase Dot1l.
AB  - The t(10;11)(p12;q23) translocation and the t(10;11)(p12;q14) translocation,
      which encode the MLL (mixed lineage leukemia)-AF10 and CALM (clathrin assembly
      lymphoid myeloid leukemia)-AF10 fusion oncoproteins, respectively, are two
      recurrent chromosomal rearrangements observed in patients with acute myeloid
      leukemia and acute lymphoblastic leukemia. Here, we demonstrate that MLL-AF10 and
      CALM-AF10-mediated transformation is dependent on the H3K79 methyltransferase
      Dot1l using genetic and pharmacological approaches in mouse models. Targeted
      disruption of Dot1l using a conditional knockout mouse model abolished in vitro
      transformation of murine bone marrow cells and in vivo initiation and maintenance
      of MLL-AF10 or CALM-AF10 leukemia. The treatment of MLL-AF10 and CALM-AF10
      transformed cells with EPZ004777, a specific small-molecule inhibitor of Dot1l,
      suppressed expression of leukemogenic genes such as Hoxa cluster genes and Meis1,
      and selectively impaired proliferation of MLL-AF10 and CALM-AF10 transformed
      cells. Pretreatment with EPZ004777 profoundly decreased the in vivo spleen-colony
      forming ability of MLL-AF10 or CALM-AF10 transformed bone marrow cells. These
      results show that patients with leukemia-bearing chromosomal translocations that
      involve the AF10 gene may benefit from small-molecule therapeutics that inhibit
      H3K79 methylation.

PMID- 23138184
TI  - Phase II study of nilotinib in patients with relapsed or refractory Philadelphia
      chromosome--positive acute lymphoblastic leukemia.

PMID- 23138185
TI  - Lenalidomide-induced upregulation of CXCR4 in CD34+ hematopoietic cells, a
      potential mechanism of decreased hematopoietic progenitor mobilization.

PMID- 23138186
TI  - Regulation of the major vacuolar Ca2+ transporter genes, by intercellular Ca2+
      concentration and abiotic stresses, in tip-burn resistant Brassica oleracea.
AB  - Calcium is an essential plant macronutrient that has unique structural and
      signaling roles related to tip-burn disorder in Brassica spp. crops. For two
      types of cabbage inbred lines, tip-burn susceptible and resistant, we measured
      and compared major macronutrient cations, including Ca(2+), in leaves. In both
      lines, Ca(2+), Mg(2+), Na(+), and K(+), accumulated more in leaf base than in
      leaf apex. Ca(2+) and K(+) were >2 times more abundant in the tip-burn resistant
      line, while Na(+) was higher in the susceptible line. Ca(2+) differences between
      the two lines resulted from differential accumulation of calcium into cell
      vacuoles. We profiled major vacuolar Ca(2+) transporters, in both cabbage lines,
      by growth time and intercellular Ca(2+) concentration. Expression pattern of
      several Ca(2+) transporter genes differed between tip-burn susceptible and
      resistant lines by growth time points. We also identified promoter regions of the
      major Ca(2+) vacuole transporter genes, CAX1, ACA4, and ACA11, which displayed
      hormonal, light and defense-related cis-acting regulatory elements. Finally,
      transporter genes in the two cabbage lines responded differently to abiotic
      stresses, demonstrating diversity in gene regulation among orthologous genes.

PMID- 23138187
TI  - Deletion of RBP-J in dendritic cells compromises TLR-mediated DC activation
      accompanied by abnormal cytoskeleton reorganization.
AB  - Dendritic cells (DCs) are professional antigen presenting cells that activate and
      modulate immune responses, but the mechanisms underlying DC activation have not
      been fully understood. In this study, we investigated the role of Notch signaling
      in DC activation by using murine bone marrow-derived DCs. Triggering of Toll-like
      receptors (TLRs) of DCs led to upregulated expression of Notch ligands.
      Disruption of Notch signaling by the deletion of RBP-J, the critical
      transcription factor mediating the canonical signaling from all Notch receptors,
      resulted in a reduced capacity of DCs in activating T cells. Moreover, RBP-J
      deficiency altered the polarization of T cell activation, as manifested by
      downregulated interferon-gamma and upregulated interleukin-4 and -10 expressions
      after LPS or Poly(I:C) stimulation. Furthermore, we found that RBP-J(-/-) DCs had
      reduced intracellular calcium after TLR-triggering. Immunofluorescent staining
      showed that RBP-J deficient DCs exhibited attenuated cytoskeleton reorganization
      when contacting T cells. In summary, our results suggested that the canonical
      Notch signaling promotes the cytoskeleton reorganization and the TLR-mediated DC
      activation.

PMID- 23138189
TI  - Plasma cyclophilin A is a novel biomarker for coronary artery disease.
AB  - BACKGROUND: Oxidative stress induces secretion of cyclophilin A (CyPA) from
      vascular smooth muscle cells and it plays a crucial role in the pathogenesis of
      atherosclerosis in mice. Therefore, we tested our hypothesis that plasma CyPA
      levels are increased in patients with coronary artery diseases (CAD). METHODS AND
      RESULTS: In 320 consecutive patients undergoing coronary angiography, we examined
      the relationship between plasma CyPA levels and the severity of CAD. We measured
      plasma CyPA by an immunoassay based on the sandwich technique. Plasma CyPA levels
      were significantly higher in patients with significant coronary stenosis compared
      to those without it (P<0.001). A positive correlation was noted between plasma
      CyPA levels and significant coronary stenosis. The average number of stenotic
      coronary arteries and the need for coronary intervention were significantly
      increased in the quartiles of higher CyPA levels (both P<0.001). Indeed, the
      plasma CyPA level significantly correlated with the presence of CAD (adjusted
      odds ratio for CAD, 6.20; 95% confidence interval, 3.14-12.27; P<0.001).
      Interestingly, plasma levels of CyPA increased according to the number of
      atherosclerotic risk factors, all of which induce oxidative stress. Furthermore,
      plasma levels of CyPA significantly reduced after medical treatment of risk
      factors. Finally, CyPA was strongly expressed in coronary atherosclerotic plaque
      in patients with myocardial infarction. CONCLUSIONS: Plasma CyPA level is a novel
      biomarker for oxidative stress and CAD in humans.

PMID- 23138190
TI  - Ex vivo  effects of low-dose rivaroxaban on specific coagulation assays and
      coagulation factor activities in patients under real life conditions.
AB  - Global coagulation assays display variable effects at different concentrations of
      rivaroxaban. The aim of this study is to quantify the  ex vivo  effects of low
      dose rivaroxaban on thrombophilia screening assays and coagulation factor
      activities  based on the administration time, and to show how to mask possible
      interferences. Plasma samples from 40 patients receiving rivaroxaban 10 mg daily
      were investigated to measure activities of clotting factor II, V, VII, VIII, IX,
      XI, XII and XIII; protein C- and protein S-levels; lupus anticoagulants;
      anticardiolipin IgG and IgM; D-dimer, heparin-platelet factor 4 (HPF4) antibodies
      and screening tests for von Willebrand disease (VWD). Two hours after 
      rivaroxaban administration, the activities of clotting factors were significantly
      decreased to different extents, except for factor XIII. Dilution of plasma
      samples resulted in neutralisation of these interferences. The chromogenic
      protein C activity assay was not affected by rivaroxaban. Depending on the timing
      of tablet intake in relation to blood sampling protein S activity was measured
      falsely high when a clotting assay was used. False-positive results for lupus
      anticoagulants were observed depending on the assay system used and the
      administration time of rivaroxaban. ELISA-based assays such as anticardiolipin
      IgG and IgM, D-dimer, HPF4-antibodies and the turbidimetric assays for VWD were
      not affected by rivaroxaban. Specific haemostasis clotting tests should be
      performed directly prior to rivaroxaban intake. Assay optimisation in the
      presence of rivaroxaban can be achieved by plasma dilution. Immunologic assays
      are not influenced by rivaroxaban, while chromogenic assays can be used, when
      they do not depend on factor Xa.

PMID- 23138191
TI  - The effect of postoperative beam, implant, and combination radiation therapy on
      GI and bladder toxicities in female Medicare beneficiaries with stage I uterine
      cancer.
AB  - OBJECTIVE: Determine the risk of late gastrointestinal (GI) and bladder
      toxicities in women treated for Stage I uterine cancer with postoperative beam,
      implant, or combination radiation.  METHODS: The Surveillance, Epidemiology, and
      End Results (SEER) tumor registry and Medicare claims were used to estimate the
      risk of developing late GI and bladder toxicities by type of radiation received.
      Bladder and GI diagnoses were identified 6-60 months after cancer diagnosis. Cox
      proportional hazard models were used to estimate risk of any late GI or bladder
      toxicity due to type of radiation received.  RESULTS: A total of 3,024 women with
      uterine cancer diagnosed from 1992-2005 were identified for analysis with a mean
      age of 73.9 (Standard Deviation (SD) +/- 6.5). Bladder and GI toxicities occurred
      most frequently in the combination group, and least in the implant group. After
      controlling for demographic characteristics, tumor grade, diagnosis year, SEER
      region, comorbidities, prior GI and bladder diagnosis, and chemotherapy, women
      receiving implant radiation had a 21% absolute decrease in GI toxicities compared
      to women receiving combination radiation (Hazard Ratio (HR) 0.79, 95% confidence
      interval (CI) 0.68-0.92). No differences were observed between those receiving
      beam and combination in GI (HR 1.01 (0.89-1.14)) and bladder (HR 0.95 (0.80
      1.11)) toxicities.  CONCLUSIONS: Older women receiving combined radiation had the
      highest rates of GI and bladder toxicities, while women receiving implant
      radiation alone had the lowest rates. When selecting type of radiation for a
      patient, these toxicities should be considered. Counseling older women surviving
      cancer on late toxicities due to radiation must be a priority for physicians
      caring for them.

PMID- 23138192
TI  - Nonvolatile multibit Schottky memory based on single n-type Ga doped CdSe
      nanowires.
AB  - Nonvolatile resistive switching has been observed for the first time in CdSe
      nanowire (NW)/Au Schottky barrier diodes, where a Schottky contact electrode and
      an Ohmic contact electrode were formed at the Au/CdSe NW and CdSe NW/In
      interfaces, respectively. The CdSe NWs Schottky devices were found to possess
      multibit storage ability in an individual nanowire, and exhibited excellent
      memory characteristics, with a resistance on/off ratio exceeding four orders of
      magnitude, a long retention time of over 10(4) s and a lower operating voltage of
      2 V. By replacing the SiO(2)/Si substrate with a poly ethylene terephthalate
      substrate, flexible and transparent memory devices with superior stability under
      strain were realized. The resistive switching of CdSe NW/Au Schottky devices is
      understood by electron trapping and detrapping in the interfacial oxide layer.
      Our findings provide a viable way to create new functional high-density
      nonvolatile multibit memory devices compatible with simple processing techniques
      for normal one-dimensional nanomaterials.

PMID- 23138193
TI  - Optofluidic imaging: now and beyond.
AB  - More than a decade of research work in optofluidics has yielded a large catalogue
      of optofluidic elements that can manipulate light at the micro-scale (e.g.,
      lenses, prisms). Although these elements have proven useful for many on-chip
      processes (e.g., miniaturized flow cytometry, interferometry and sample
      spectroscopy), certain deficiencies have precluded their use in micro-scale
      imaging. However, recent work in optofluidic imaging has avoided optofluidic
      elements entirely and focused instead on image capture and composition
      techniques, demonstrating impressive resolution in both 2D imagery and 3D
      tomography. In this Focus article, we will discuss some of the recent successes
      in optofluidic imaging and will expound our expectations for the near future of
      the optofluidic imaging discipline.

PMID- 23138194
TI  - Clinical symptoms of ADHD and psychopathy in perpetrators.
AB  - ADHD and psychopathy are both associated with poor social adaptation and
      antisocial behavior. Previous studies have also suggested that ADHD and
      psychopathy share some symptomatology. The current study attempted to further
      uncover the relationship between ADHD and psychopathy in perpetrators by
      investigating the possibility of underlying common factors of ADHD and
      psychopathy using standardized instruments. Correlation analyses and principal
      component analyses were performed on ADHD-SB self-rating questionnaires and the
      PCL-SV from a population of 314 offenders. Further, subjects without ADHD, full
      ADHD and partially remitted ADHD according to DSM-IV were compared regarding
      psychopathic traits. ADHD and psychopathy rating scores were found to be
      correlated. Only psychopathic features related to unstable and antisocial
      lifestyle, but not related to affective features of psychopathy accounted to this
      association. Findings on the principal component analysis suggest that ADHD and
      psychopathy are unrelated on a symptomatic level, with the exception of
      impulsivity, which is a common feature that seems to combine both constructs.

PMID- 23138195
TI  - Association between degrees of social defeat and themes of delusion in patients
      with schizophrenia from immigrant and ethnic minority backgrounds.
AB  - Immigrants have a heightened risk of developing schizophrenia, suggesting that
      social factors play an important role in the pathogenesis of schizophrenia. This
      study aimed to examine the relationship between degrees of social defeat and
      themes of delusion in patients with schizophrenia from immigrant and ethnic
      minority backgrounds. Retrospective chart review was conducted. Patients'
      psychosocial history, particularly employment history, level of education, and
      subjective feelings of societal integration before and after immigration, were
      compared to determine the degree of social defeat. It was found that delusional
      themes of psychological persecution, such as control and reference, were more
      common in those with either moderate or severe degrees of social defeat.

PMID- 23138197
TI  - Hemicryptophane-assisted electron transfer: a structural and electronic study.
AB  - Three copper(II)@hemicryptophane complexes with various cavity sizes and shapes,
      Cu(II)@1, Cu(II)@2 and Cu(II)@3, were synthesized and characterized by near
      IR/vis and EPR spectroscopies. The spectroscopic data are consistent with the
      presence of a trigonal-bipyramidal geometry of the N(4)Cu.H(2)O core, in accord
      with the energy-minimized structures obtained from DFT calculations. Cyclic
      voltammetry studies in CH(2)Cl(2) showed irreversible redox processes, whereas
      electrolysis coulometry indicated that Cu(II)/Cu(I) complexes could be
      interconverted. Electrochemistry data of the complexes stress the crucial role of
      the cage structure of the hemicryptophane in the thermodynamics of the electron
      transfer.

PMID- 23138198
TI  - Association of promoter methylation and 32-bp deletion of the PTEN gene with
      susceptibility to metabolic syndrome.
AB  - Metabolic syndrome (MeS), a cluster of several metabolic disorders, is
      increasingly being recognized as a risk factor for type II diabetes (T2D) and
      cardiovascular disease. Genetic and epigenetic alteration of the phosphatase and
      tensin homolog deleted on chromosome ten (PTEN) has been associated with
      components of MeS. The aim of the present study was to investigate the possible
      association of a 32-bp deletion polymorphism and promoter methylation of the PTEN
      gene with MeS. DNA was extracted from the peripheral blood of 151 subjects with
      and 149 subjects without MeS. The 32-bp deletion variant of PTEN was detected by
      polymerase chain reaction (PCR) and PTEN promoter methylation was defined by a
      nested methylation-specific PCR (MSP) method. No significant differences were
      found in the allelic and genotypic frequencies of the 32-bp deletion variant of
      PTEN between the groups [odds ratio (OR), 0.77; 95% confidence interval (CI),
      0.41-1.45; P=0.431]. However, patients with MeS were identified to have lower
      levels of PTEN promoter hypermethylation than subjects without MeS. Promoter
      methylation may be a protective factor against susceptibility to MeS (OR, 0.52;
      95% CI, 0.29-0.92; P=0.029). Our findings suggest that PTEN promoter methylation
      may be a mechanism for PTEN downregulation or silencing in MeS, which remains to
      be fully clarified. 

PMID- 23138199
TI  - A comparison of surgical outcomes with the use of 2 different biodegradable
      multipoint fixation devices for endoscopic forehead elevation.
AB  - PURPOSE: To assess the efficacy and rates of inflammatory cyst formation with the
      use of 2 different biodegradable multipoint fixation devices, Endotine versus
      Ultratine, for endoscopic forehead elevation. METHODS: The charts of 138 patients
      who underwent endoscopic forehead elevation by the same surgeon (E.H.B.) were
      reviewed retrospectively. Data regarding patient demographics, type of
      biodegradable fixation device, loss of fixation in the immediate and late
      postoperative period, inflammatory cyst formation of the fixation device,
      additional complications, and reoperation status were collected from the charts.
      Patients implanted with Endotine and Ultratine were compared postoperatively for
      early and late loss of elevation (efficacy), inflammatory cyst formation,
      additional complications, and reoperation rates. RESULTS: Of the 276 fixation
      devices implanted (117 Endotine and 159 Ultratine), 11 inflammatory cysts were
      found, all of them in the Ultratine group (p = 0.0037). Four patients required
      reoperation due to early loss of fixation. Three of these cases were in the
      Endotine group, and 1 case was observed in the Ultratine group (p = 0.18). A
      total of 4 patients had late loss of fixation, all of them in the Ultratine group
      (p = 0.08). Scalp hypoesthesia and/or dysesthesia beyond the sixth postoperative
      month were observed in 3.62% of the cases. Postsurgical neuralgia was observed in
      2.17%, and focal alopecia was seen in 1.44%. CONCLUSIONS: The presence of
      inflammatory cysts with the implantation of the Ultratine device is statistically
      higher than with Endotine. No statistical significant difference was found in
      either early or late fixation loss between the 2 groups.

PMID- 23138200
TI  - Osteotome as an adjunctive instrument in endoscopic dacryocystorhinostomy.
AB  - PURPOSE: To report the novel use of the osteotome as an adjunctive instrument in
      Endoscopic Dacryocystorhinostomy (DCR). MATERIALS AND METHODS: A retrospective
      interventional case series of 15 patients, underwent endoscopic DCR at the
      Singapore National Eye Centre, by a single ophthalmologist and rhinologist
      between April 2009 and April 2011.All patients' case records were reviewed and
      the information recorded included: patients' demographics, level of obstruction
      of the lacrimal system, operative time, postoperative symptoms and complications
      (if any), and the length of follow-up. All patients had preoperative syringing to
      determine the level of obstruction, and had postoperative syringing only if there
      were any complaints of epiphora.All surgeries were recorded on video. The
      osteotome and mallet were used in all patients to augment the bone removal, and
      Crawford stent (MIRA(r)) intubation was done in all patients and left in situ for
      2 months. RESULTS: A total of 15 patients were reviewed and analyzed from April
      2009 to August 2010. Ages ranged from 22 to 77 years of age underwent endoscopic
      DCR with Crawford stent (MIRA (r)) intubation. All patients had syringing before
      surgery and all had only nasolacrimal duct obstruction except 1 patient who had
      common canalicular obstruction. The surgery was carried out as described above
      with no intraoperative or postoperative complications in any of the patients.
      Duration of surgery ranged from 22 to 65 minutes with a mean time of 42.6
      minutes. All patients were followed up from 2 to 11 months with resolution of
      epiphora in all cases. CONCLUSION: The use of the osteotome and mallet, in
      combination with the Kerrison rongeur and diamond drill, has been found to be
      useful in creating a large osteotomy in endoscopic DCR. It has allowed greater
      ease and speed in performing this procedure, especially for patients with thicker
      bone and narrower nasal cavities.

PMID- 23138202
TI  - Pre- and postoperative quantitative analysis of contour abnormalities in Graves
      upper eyelid retraction.
AB  - PURPOSE: One of the most common problems of the surgical management of Graves
      upper eyelid retraction is the occurrence of eyelid contour abnormalities. In the
      present study, the postoperative contour of a large sample of eyelids of patients
      with Graves orbitopathy was measured. METHODS: The postoperative upper eyelid
      contour of 62 eyes of 43 patients with Graves orbitopathy was subjectively
      classified by 3 experienced surgeons in 3 categories: poor, fair, and good. The
      shape of the eyelid contours in each category was then measured with a recently
      developed custom-made software by measuring multiple midpupil eyelid distances
      each 15 degrees  along the palpebral fissure. The upper eyelid contour of 60
      normal subjects was also quantified as a control group. RESULTS: The mean ratio
      between the sum of the lateral and medial midpupil eyelid distances
      (lateral/medial ratio) was 1.10 +/- 0.11 standard deviation in controls and 1.15
      +/- 0.13 standard deviation in patients. Postoperatively, the mean midpupil
      eyelid distance at 90 degrees  was 4.16 +/- 1.13 mm standard deviation. The
      distribution lateral/medial ratios of the eyelids judged as having good contours
      was similar to the distribution of the controls with a modal value centered on
      the interval between 1.0 and 1.10. The distribution of lateral/medial ratios of
      the eyelids judged as having poor contour was bimodal, with eyelids with low and
      high lateral/medial ratios. Low lateral/medial ratios occurred when there was a
      lateral overcorrection, giving the eyelid a flat or a medial ptosis appearance.
      High lateral/medial ratios were due to a central or medial overcorrection or a
      lateral peak maintenance. CONCLUSIONS: Postoperative upper eyelid contour
      abnormalities can be quantified by comparing the sum of multiple midpupil eyelid
      distances of the lateral and medial sectors of the eyelid. Low and high
      lateral/medial ratios are anomalous and judged as unpleasant.

PMID- 23138201
TI  - Aesthetic considerations in upper eyelid retraction surgery.
AB  - PURPOSE: Classically, the aesthetic outcomes of eyelid retraction surgery in
      patients with thyroid-associated orbitopathy have been described in reference to
      eyelid margin position and marginal reflex distance. A critically important
      component of upper eyelid contour is the tarsal platform show (TPS). With this
      study, the authors aimed to assess the hypothesis that modification of the tarsal
      platform in posterior eyelid retraction surgery has a significant effect on the
      final aesthetic outcome. METHODS: In a retrospective, observational, case-cohort
      study, the authors reviewed the medical records of 36 patients with thyroid
      associated orbitopathy who underwent primary eyelid retraction surgery by 1
      surgeon. Patients who underwent eyelid retraction surgery at the time of orbital
      decompression were excluded. The surgical technique consisted of posterior
      approach conjunctival release of Mueller muscle and graded recession of the
      levator aponeurosis. To address lateral flare, dissection was carried toward the
      lateral orbital rim with spreading of the lateral horn of the levator
      aponeurosis. Outcome measures were millimeters of TPS, millimeters of brow fat
      span, and symmetry of the eyelid margin position. Randomized preoperative and
      postoperative standardized photographs were evaluated in masked fashion by 4
      surgeons to grade cosmetic outcomes. RESULTS: Fifteen patients (24 eyelids) met
      the inclusion criteria. Mean follow-up period was 6 months (range, 3-12). Mean
      TPS increased from 2.27 mm (standard deviation, 1.9 mm) to 4.77 mm (standard
      deviation, 1.7 mm; p < 0.05). Mean brow fat span remained unchanged, from 13.22
      mm (standard deviation, 2.2 mm) to 13.25 mm (standard deviation, 1.9; p > 0.05).
      Evaluation of the aesthetic outcomes (eyelid contour, eyelid symmetry, and TPS)
      by 4 masked observers characterized the relevance of TPS in the postoperative
      aesthetics of eyelid contour and symmetry. CONCLUSIONS: In upper eyelid
      retraction surgery, the ability to control the TPS has a significant impact on
      the final aesthetic outcome. Posterior approach eyelid retraction surgery can
      control eyelid contour and can represent an ideal surgical approach in carefully
      selected patients. However, it has limited ability to control upper orbital
      volume and eyebrow and orbital fat (brow fat span). This can result in relative
      overelongation of the TPS. Factors such as ethnic characteristics, bony
      asymmetry, brow fat span, and premorbid TPS influence cosmetic outcomes achieved
      by the anterior or posterior approach. For optimal aesthetic results in eyelid
      retraction surgery, the decision for anterior versus posterior approach should be
      individualized.

PMID- 23138203
TI  - Angiomyofibroma of the orbit:  a hybrid of vascular leiomyoma and cavernous
      hemangioma.
AB  - PURPOSE: The aim of this study was to describe a novel primary orbital vascular
      tumor combining elements of a vascular leiomyoma (angioleiomyoma) and a cavernous
      hemangioma. METHODS: A critical review of clinical records, diagnostic tests, and
      radiographic studies combined with histopathologic evaluation with standard and
      special histochemical staining and immunohistochemical investigations was
      conducted. RESULTS: A 44-year-old man slowly developed 5 mm of well-tolerated
      relative right proptosis with minimal motility disturbance and no visual decline.
      Computed tomography and magnetic resonance imaging demonstrated a medial and
      intraconal rounded mass that perfused slowly and whose anterior surface was well
      circumscribed. At surgery, the tumor was solid and pink with intersecting white
      bands and densely attached to surrounding normal tissues. The most adherent
      apical portion of the mass was left behind after subtotal excision.
      Histopathologically, only a partial pseudocapsule was discovered. The tumor was
      composed of cavernous channels, capillary zones, compressed lumens with linear
      strands of endothelium, and collections of muscular veins devoid of an elastica.
      Striking smooth muscle actin positivity was identified in disorganized masses of
      smooth muscle cells in the intervascular spaces and around the cavernous vascular
      units; these myocytes were intermixed with bundles of interstitial keloidal
      collagen. The endothelium was CD31 and CD34 positive for vascular endothelium and
      D2-40 negative for lymphatic endothelium. CONCLUSIONS: The authors have
      classified this hybrid tumor an angiomyofibroma with low neoplastic potential and
      features of a malformation. It is a composite variant of cavernous hemangioma
      associated with a conspicuous proliferation of anomalous disorganized smooth
      muscle cells (leiomyoma). Most of the lesion lacked a pseudocapsule, which
      impeded surgical delivery. Incomplete excision is recommended in such cases as
      preferable to the complications that could ensue from overly aggressive efforts
      at complete removal, particularly at the orbital apex. Supporting this position
      is the observation that incompletely excised cavernous hemangioma generally does
      not recur.

PMID- 23138204
TI  - The sigmoid upper eyelid blepharoplasty:  commentary.

PMID- 23138205
TI  - The sigmoid upper eyelid blepharoplasty:  commentary.

PMID- 23138206
TI  - Treatment of malar festoon using modified subperiosteal midface lift.
AB  - PURPOSE: To describe a technique for treatment of malar festoons with partial
      subperiosteal midface lift, lower eyelid tarsal strips, and orbicularis muscle
      skin flaps. METHODS: Retrospective case report. RESULTS: A 55-year-old Caucasian
      man developed extensive festoons on both cheeks shortly after deep brain
      stimulator surgery. The described surgical technique resulted in significant
      reduction in his festoons. This approach avoided direct excision of the festoon
      and made use of a more easily hidden incision. CONCLUSIONS: Festoons of the
      midface have been described in the literature, but little data exist regarding
      the ideal treatment for this difficult to manage problem. We report successful
      treatment of festoons with a modified subperiosteal midface lift.

PMID- 23138207
TI  - Re: "Direct fixation of extraocular muscles to a silicone sphere: a cost
      sensitive, low-risk enucleation procedure".

PMID- 23138209
TI  - Re: "Human immunodeficiency virus-associated blepharoptosis".

PMID- 23138211
TI  - Re: "Radiographic predictors of visual outcome in orbital compartment syndrome".

PMID- 23138213
TI  - Re: "Sentinel lymph node biopsy in patients with conjunctival and eyelid cancers:
      experience in 17 patients".

PMID- 23138215
TI  - Re: "The lower lid diamond: a simple entropion repair to correct both horizontal
      and lower-lid retractor laxity".

PMID- 23138217
TI  - Pig eyelid as a teaching model for severe ptosis repair.

PMID- 23138218
TI  - Extracting CT and MRI images from CD-ROM.

PMID- 23138219
TI  - An argument for "closed canthal suspension" in aesthetic lower blepharoplasty.

PMID- 23138220
TI  - Blepharospasm cause and treatment: YouTube as a reflection of current popular
      thought.

PMID- 23138221
TI  - Demographic characteristics of patients requiring full-thickness skin grafts for
      cicatricial ectropion at Duke Eye Center from 2000 to 2010.

PMID- 23138222
TI  - [Drug-induced seizures].
AB  - Drug-induced seizures are in view of a constantly ageing population and
      increasingly frequent polypharmacotherapy an increasing problem in daily routine
      praxis. Identification of potentially seizure-inducing drugs may help generating
      risk profiles for individual patients. Drug-induced seizures have often been seen
      as a complication of psychopharmacological therapy, but its occurrence has also
      been described in response to a great diversity of compounds such as antibiotics,
      sympathomimetics and anaesthetics. The present article outlines a synopsis of the
      most prevalent seizure-inducing drugs as well as strategies how to deal with a
      patient suffering from a drug-induced seizure.

PMID- 23138223
TI  - Graphitic carbon nitride (g-C3N4)-Pt-TiO2 nanocomposite as an efficient
      photocatalyst for hydrogen production under visible light irradiation.
AB  - Porous graphitic carbon nitride (g-C(3)N(4)) was prepared by a simple pyrolysis
      of urea, and then a g-C(3)N(4)-Pt-TiO(2) nanocomposite was fabricated via a
      facile chemical adsorption followed by a calcination process. The obtained
      products were characterized by X-ray diffraction, X-ray photoelectron
      spectroscopy, UV-vis diffuse reflectance absorption spectra, and electron
      microscopy. It is found that the visible-light-induced photocatalytic hydrogen
      evolution rate can be remarkably enhanced by coupling TiO(2) with the above g
      C(3)N(4), and the g-C(3)N(4)-Pt-TiO(2) composite with a mass ratio of 70 : 30 has
      the maximum photoactivity and excellent photostability for hydrogen production
      under visible-light irradiation, and the stable photocurrent of g-C(3)N(4)-TiO(2)
      is about 1.5 times higher than that of the bare g-C(3)N(4). The above
      experimental results show that the photogenerated electrons of g-C(3)N(4) can
      directionally migrate to Pt-TiO(2) due to the close interfacial connections and
      the synergistic effect existing between Pt-TiO(2) and g-C(3)N(4) where
      photogenerated electrons and holes are efficiently separated in space, which is
      beneficial for retarding the charge recombination and improving the
      photoactivity.

PMID- 23138224
TI  - Genome-wide mapping of methylated adenine residues in pathogenic Escherichia coli
      using single-molecule real-time sequencing.
AB  - Single-molecule real-time (SMRT) DNA sequencing allows the systematic detection
      of chemical modifications such as methylation but has not previously been applied
      on a genome-wide scale. We used this approach to detect 49,311 putative 6
      methyladenine (m6A) residues and 1,407 putative 5-methylcytosine (m5C) residues
      in the genome of a pathogenic Escherichia coli strain. We obtained strand
      specific information for methylation sites and a quantitative assessment of the
      frequency of methylation at each modified position. We deduced the sequence
      motifs recognized by the methyltransferase enzymes present in this strain without
      prior knowledge of their specificity. Furthermore, we found that deletion of a
      phage-encoded methyltransferase-endonuclease (restriction-modification; RM)
      system induced global transcriptional changes and led to gene amplification,
      suggesting that the role of RM systems extends beyond protecting host genomes
      from foreign DNA.

PMID- 23138225
TI  - Energy extraction from the biologic battery in the inner ear.
AB  - Endocochlear potential (EP) is a battery-like electrochemical gradient found in
      and actively maintained by the inner ear. Here we demonstrate that the mammalian
      EP can be used as a power source for electronic devices. We achieved this by
      designing an anatomically sized, ultra-low quiescent-power energy harvester chip
      integrated with a wireless sensor capable of monitoring the EP itself. Although
      other forms of in vivo energy harvesting have been described in lower organisms,
      and thermoelectric, piezoelectric and biofuel devices are promising for mammalian
      applications, there have been few, if any, in vivo demonstrations in the vicinity
      of the ear, eye and brain. In this work, the chip extracted a minimum of 1.12 nW
      from the EP of a guinea pig for up to 5 h, enabling a 2.4 GHz radio to transmit
      measurement of the EP every 40-360 s. With future optimization of electrode
      design, we envision using the biologic battery in the inner ear to power chemical
      and molecular sensors, or drug-delivery actuators for diagnosis and therapy of
      hearing loss and other disorders.

PMID- 23138226
TI  - The in vitro and in vivo antioxidant properties of Cyperus esculentus oil from
      Xinjiang, China.
AB  - BACKGROUND: Cyperus esculentus oil is also known as the new health care oil. This
      study aimed to analyse the fatty acid profile and content of C. esculentus oil by
      gas chromatography-mass spectrometry and to assess the antioxidant activity of C.
      esculentus oil. These properties were evaluated based on the reducing power,
      hydroxyl radical and diphenyl picryl hydrazyl radical scavenging, and a
      combination of in vitro and in vivo antioxidant experiments. RESULTS: Composition
      analyses showed that C. esculentus oil contained more than 800 g kg(-1)
      unsaturated fatty acid, of which oleic acid accounted for 691.4 g kg(-1),
      linoleic acid accounted for 107.0 g kg(-1) and palmitic acid accounted for 158.0
      g kg(-1). In vitro results showed that the total antioxidant activity and the
      scavenging capacity of hydroxyl radicals and diphenyl picryl hydrazyl radicals
      increased with increasing concentration. The in vitro antioxidant ability
      increased as the concentration of C. esculentus oil, with 15 mL kg(-1) BW day(-1)
      being established as the optimal dose. CONCLUSION: Taken together, the results of
      this study clearly indicate that C. esculentus oil has good antioxidant
      properties.

PMID- 23138227
TI  - Characterization of the interaction between arginine kinase and siRNA.
AB  - RNAi, a crucial pathway in animals to defend against virus infection, is mediated
      directly by RNA-induced silencing complex (RISC) in an ATP-dependent manner. The
      RISC comprises one strand of short interfering RNA (siRNA) and multiprotein
      including Argonaute protein, which can cleave target RNAs. However, the proteins
      interacted with siRNA are not extensively explored. In this study, an antiviral
      siRNA (vp28-siRNA) targeting the vp28 gene of shrimp white spot syndrome virus
      was characterized. Based on the biotin/streptavidin affinity screening, it was
      found that the shrimp arginine kinase was specifically bound with the vp28-siRNA.
      The co-immunoprecipitation assays revealed that the siRNA was directly interacted
      with arginine kinase, suggesting that arginine kinase was an essential component
      of RNA-induced silencing complex. Therefore, our study presented a novel finding
      on the RISC components, which would be helpful to reveal the molecular events in
      the RNAi pathway.

PMID- 23138228
TI  - Inhibition of cyclin-dependent kinase 6 suppresses cell proliferation and
      enhances radiation sensitivity in medulloblastoma cells.
AB  - Medulloblastoma accounts for 20 % of all primary pediatric intracranial tumors.
      Current treatment cures 50-80 % of patients but is associated with significant
      long-term morbidity and thus new therapeutic targets are needed. One such target
      is cyclin-dependent kinase 6 (CDK6), a serine/threonine kinase that plays a vital
      role in cell cycle progression and differentiation. CDK6 is overexpressed in
      medulloblastoma patients and is associated with an adverse prognosis. To
      investigate the role of CDK6 in medulloblastoma, we assayed the effect of CDK6
      inhibition on proliferation by depleting expression with RNA interference (RNAi)
      or by inhibiting kinase function with a small molecule inhibitor, PD0332991. Cell
      proliferation was assessed by colony focus assay or by the xCELLigence system. We
      then investigated the impact of CDK6 inhibition on differentiation of murine
      neural stem cells by immunofluorescence of relevant markers. Finally we evaluated
      the effects of PD0332991 treatment on medulloblastoma cell cycle and
      radiosensitivity using colony focus assays. Gene expression analysis revealed
      that CDK6 mRNA expression is higher than normal cerebellum in fifteen out of
      sixteen medulloblastoma patient samples. Inhibition of CDK6 by RNAi significantly
      decreased medulloblastoma cell proliferation and colony forming potential.
      Interestingly, CDK6 inhibition by RNAi increased differentiation in murine neural
      stem cells. PD0332991 treatment significantly decreased medulloblastoma cell
      proliferation and led to a G0/G1 cell cycle arrest. Furthermore, PD0332991
      pretreatment sensitized medulloblastoma cells to ionizing radiation. Our findings
      suggest that targeting CDK6 with small molecule inhibitors may prove beneficial
      in the treatment of medulloblastoma, especially when combined with radiation.

PMID- 23138229
TI  - Functional contributions of the plasma membrane calcium ATPase and the sodium
      calcium exchanger at mouse parallel fibre to Purkinje neuron synapses.
AB  - We investigated how two calcium clearance mechanisms, the sodium-calcium
      exchanger-NCX, and the plasma membrane calcium ATPase-PMCA2, function at the
      facilitating cerebellar parallel fibre to Purkinje neuron (PF-PN) synapse.
      Forward mode NCX helped recover PF presynaptic calcium elevations when the PFs
      received a double stimulation and the calcium load was sufficiently high. A
      smaller presynaptic calcium load evoked by a single PF stimulation failed to
      recruit NCX in wild-type mice but did so when PMCA2 was absent in PFs from PMCA2
      knockout mice. Simulated calcium dynamics using a simple single-compartment model
      reported qualitatively similar effects. Functionally, reduced NCX activity in the
      absence of PMCA also prolonged the recovery of facilitation at the PF-PN synapse,
      beyond that seen by reduced NCX activity alone. We conclude that PMCA and NCX
      work in parallel to accurately shape residual presynaptic calcium recovery
      dynamics and fine-tune facilitation at this important cerebellar synapse.

PMID- 23138231
TI  - Seasonal forcing and multi-year cycles in interacting populations: lessons from a
      predator-prey model.
AB  - Many natural systems are subject to seasonal environmental change. As a
      consequence many species exhibit seasonal changes in their life history
      parameters--such as a peak in the birth rate in spring. It is important to
      understand how this seasonal forcing affects the population dynamics. The main
      way in which seasonal models have been studied is through a two dimensional
      bifurcation approach. We augment this bifurcation approach with extensive
      simulation in order to understand the potential solution behaviours for a
      predator-prey system with a seasonally forced prey growth rate. We consider
      separately how forcing influences the system when the unforced dynamics have
      either monotonic decay to the coexistence steady state, or oscillatory decay, or
      stable limit cycles. The range of behaviour the system can exhibit includes multi
      year cycles of different periodicities, parameter ranges with coexisting multi
      year cycles of the same or different period as well as quasi-periodicity and
      chaos. We show that the level of oscillation in the unforced system has a large
      effect on the range of behaviour when the system is seasonally forced. We discuss
      how the methods could be extended to understand the dynamics of a wide range of
      ecological and epidemiological systems that are subject to seasonal changes.

PMID- 23138230
TI  - Multiplexed visualization of dynamic signaling networks using genetically encoded
      fluorescent protein-based biosensors.
AB  - Cells rely on a complex, interconnected network of signaling pathways to sense
      and interpret changes in their extracellular environment. The development of
      genetically encoded fluorescent protein (FP)-based biosensors has made it
      possible for researchers to directly observe and characterize the spatiotemporal
      dynamics of these intracellular signaling pathways in living cells. However,
      detailed information regarding the precise temporal and spatial relationships
      between intersecting pathways is often lost when individual signaling events are
      monitored in isolation. As the development of biosensor technology continues to
      advance, it is becoming increasingly feasible to image multiple FP-based
      biosensors concurrently, permitting greater insights into the intricate
      coordination of intracellular signaling networks by enabling parallel monitoring
      of distinct signaling events within the same cell. In this review, we discuss
      several strategies for multiplexed imaging of FP-based biosensors, while also
      underscoring some of the challenges associated with these techniques and
      highlighting additional avenues that could lead to further improvements in
      parallel monitoring of intracellular signaling events.

PMID- 23138232
TI  - Ethics, finance, and automation: a preliminary survey of problems in high
      frequency trading.
AB  - All of finance is now automated, most notably high frequency trading. This paper
      examines the ethical implications of this fact. As automation is an
      interdisciplinary endeavor, we argue that the interfaces between the respective
      disciplines can lead to conflicting ethical perspectives; we also argue that
      existing disciplinary standards do not pay enough attention to the ethical
      problems automation generates. Conflicting perspectives undermine the protection
      those who rely on trading should have. Ethics in finance can be expanded to
      include organizational and industry-wide responsibilities to external market
      participants and society. As a starting point, quality management techniques can
      provide a foundation for a new cross-disciplinary ethical standard in the age of
      automation. 

PMID- 23138233
TI  - Osteolysis of the tibial plateau after meniscal repair with hybrid suture anchor.
AB  - Preservation of the meniscus and consideration for repair is important when
      treating meniscal tears. Many techniques for repair have been described. At
      present, all-inside, suture anchor-based meniscal repair systems are widely used.
      Arthroscopic all-inside hybrid meniscal suturing has been shown to have a low
      complication rate as the suture anchors remain outside the capsule leaving only
      the suture material inside the joint. Complications such as chondrolysis or
      arthrolysis have not been reported with these devices until now. The purpose of
      our study is to highlight the risks of osteochondral damage if these devices
      persist intra-articularly. LEVEL OF EVIDENCE: IV.

PMID- 23138234
TI  - Dopamine receptor 1 modulates the discharge activities of inspiratory and
      biphasic expiratory neurons via cAMP-dependent pathways.
AB  - Dopamine receptor 1 (D(1)R) plays an essential role in regulating respiratory
      activity in mammals, however, little is known about how this receptor acts to
      modulate the basic respiratory rhythmogenesis. Here, by simultaneously recording
      the discharge activities of biphasic expiratory (biphasic E) neurons/inspiratory
      (I) neurons and the XII nerve rootlets from brainstem slices, we found that the
      application of D(1)R agonist cis-(+/-)-1-(aminomethyl)-3,4-dihydro-3-phenyl-1H-2
      benzopyran-5,6-diolhydrochloride (A68930, 5 MUM), or forskolin, an intracellular
      cAMP-increasing agent, substantially decreased respiratory cycle and expiratory
      time of both types of neurons, and elevated the integral amplitude and frequency
      of XII nerve rootlets discharge. These changes were reversed by subsequent
      application of their antagonists SCH-23390 and Rp-Adenosine 3',5'-cyclic
      monophosphorothioate triethylammonium salt hydrate (Rp-cAMPS), respectively.
      Importantly, after pretreatment with Rp-cAMPS, the effects of A68930 in both
      types of neurons were blocked, suggestive of a cAMP-dependent action of A68930.
      Thus, the current study indicates that D(1)R may modulate basic breathing
      rhythmogenesis via cAMP-dependent mechanisms.

PMID- 23138235
TI  - Risk of revision for fixed versus mobile-bearing primary total knee replacements.
AB  - BACKGROUND: Mobile-bearing total knee arthroplasty prostheses were developed to
      reduce wear and revision rates; however, these benefits remain unproven. The
      purposes of this study were to compare the short-term survivorship and to
      determine risk factors for revision of mobile-bearing and fixed-bearing total
      knee replacements. METHODS: A prospective cohort study of primary total knee
      arthroplasties performed from 2001 to 2009 was conducted with use of a community
      total joint replacement registry. Patient characteristics and procedure details
      were identified. Cox regression models were used. Bearing type was investigated
      as a risk factor for revision while adjusted for other risk factors such as age,
      American Society of Anesthesiologists (ASA) score, body mass index, sex, race,
      diagnosis, bilateral procedures, cruciate-retaining versus posterior-stabilized
      components, surgical approach, fixation, patellar resurfacing, hospital and
      surgeon volumes, and fellowship training. RESULTS: The study cohort consisted of
      47,339 total knee arthroplasties, with 62.6% of the procedures in women. Fixed
      bearings were used in 41,908 knees (88.5%) and mobile bearings in 4830 (10.2%).
      Rotating-platform designs were used in all mobile-bearing total knee
      arthroplasties (3112 had a Rotating-Platform Press-Fit Condylar posterior
      stabilized design; 1053, a Low Contact Stress [LCS] design; and 665, a Rotating
      Platform Press-Fit Condylar cruciate-retaining design). Patients who received
      fixed-bearing total knee arthroplasty systems were older (mean age, 68.1 years)
      than those who received mobile-bearing total knee arthroplasty systems (mean age,
      62.2 years); the difference was significant (p < 0.001). Overall, 515 knees
      (1.1%) were revised for reasons other than infection. The survival rate was 97.8%
      (95% confidence interval [CI], 97.4% to 98.0%) at 6.7 years. The adjusted risk of
      aseptic revision for the LCS total knee replacements was 2.01 times (95% CI, 1.41
      to 2.86) higher than that for fixed-bearing total knee replacements (p <
      0.001).There was no significant revision risk for the other mobile-bearing total
      knee arthroplasty systems. There was no association with surgeon and hospital
      case volumes and the risk of revision total knee arthroplasty. CONCLUSIONS: Our
      study suggests the benefit of potential long-term wear reduction with the LCS
      implant may not be realized in a community-based setting, where a variety of
      surgical skills, surgical experience, and diverse patient demographic factors may
      affect early outcomes. LEVEL OF EVIDENCE: Therapeutic Level II.

PMID- 23138236
TI  - Arthroscopically pertinent anatomy of the anterolateral and posteromedial bundles
      of the posterior cruciate ligament.
AB  - BACKGROUND: The clock-face method to identify the femoral posterior cruciate
      ligament (PCL) attachment has poor accuracy and reproducibility. Measurements of
      clinically relevant anatomic structures would provide more useful surgical
      guidance. The purpose of the present study was to describe the attachments of the
      anterolateral and posteromedial bundles of the PCL relative to relevant landmarks
      to assist with arthroscopic anatomic PCL reconstructions. METHODS: Dissections
      were performed on twenty nonpaired fresh-frozen cadaveric knees. RESULTS: The
      distal articular cartilage margin of the intercondylar notch had a consistent
      shape conforming to the attachments of the anterolateral and posteromedial
      bundles. The mean distance (and standard deviation) between the femoral centers
      of the anterolateral and posteromedial bundles was 12.1 +/- 1.3 mm. The distal
      margins of the anterolateral and posteromedial bundles were a mean of 1.5 +/- 0.8
      mm and 5.8 +/- 1.7 mm proximal to the notch articular cartilage, respectively. On
      the tibia, the lateral plateau articular cartilage, the medial meniscus
      attachment, and an osseous ridge ("bundle ridge") separating the anterolateral
      and posteromedial bundles were important arthroscopic landmarks. The mean
      distance between the tibial centers of the anterolateral and posteromedial
      bundles was 8.9 +/- 1.2 mm. CONCLUSIONS: The pertinent landmarks identified
      during arthroscopic PCL reconstruction consistently marked the borders of the
      attachments of the anterolateral and posteromedial bundles. To guide femoral
      tunnel placement, the centers of both bundles should be triangulated relative to
      the reported landmarks. Furthermore, the distal edge of the femoral anterolateral
      bundle should be placed adjacent to the articular cartilage, whereas the
      posteromedial bundle should be centered, on average, 8.6 mm proximal to the
      cartilage margin, just distal to the medial intercondylar ridge. On the tibia,
      the PCL tunnel should be placed just anterosuperior to the bundle ridge, with use
      of the lateral articular cartilage and medial meniscus attachment to guide
      placement. CLINICAL RELEVANCE: The results of the present study can assist with
      more anatomic tunnel placement during single and double-bundle PCL
      reconstructions. The results also suggest that two reconstruction tunnels are
      needed to reconstruct the broad femoral attachment, whereas one reconstruction
      tunnel should be investigated further for the compact tibial attachment.

PMID- 23138237
TI  - Hemostatic techniques reduce hospital stay following multilevel posterior
      cervical spine surgery.
AB  - BACKGROUND: Despite meticulous hemostasis, persistent postoperative drain output
      following posterior cervical spine procedures often necessitates a prolonged
      length of hospital stay. We sought to determine if thrombin-soaked absorbable
      gelatin compressed sponge can decrease postoperative drain output and the length
      of hospital stay after multilevel posterior cervical spine surgery. METHODS: We
      performed a retrospective analysis of forty-three pairs of patients who had
      undergone either posterior cervical decompression and/or fusion of three or more
      levels by the same surgeon. The patients were matched according to intraoperative
      blood loss, age, sex, and number of involved levels. Control patients were
      managed between 2004 and 2007, whereas study patients were managed between 2008
      and 2011. The only variable between the study and control groups was that, in the
      study group, absorbable gelatin compressed sponge was soaked in thrombin and
      applied over the exposed spine before wound closure. A subfascial drain was used
      in all patients. Total drain output, time for the drainage to decrease to <30 mL
      per eight-hour shift (at which point the drain was discontinued), the length of
      stay, the number of readmissions, and postoperative complications were analyzed.
      RESULTS: Total drain output averaged 93 mL in the study group and 204 mL in the
      control group (p < 0.0001). The average time for the drainage to decrease to <30
      mL per eight-hour shift was 2.5 shifts in the study group and 4.4 shifts in the
      control group (p < 0.0001). Length of stay averaged 1.3 days (cumulative total,
      fifty-seven days) in the study group and 2.2 days (cumulative total, ninety-five
      days) in the control group (p < 0.0001). Persistent drain output was the primary
      reason preventing discharge on the first postoperative day. There were no
      infections, epidural hematomas, or readmissions within thirty days of discharge
      in either group. No patient developed adverse reactions attributable to the
      thrombin-soaked absorbable gelatin compressed sponge. CONCLUSIONS: Application of
      thrombin-soaked absorbable gelatin compressed sponge at the end of multilevel
      posterior cervical spinal surgery significantly decreased postoperative drain
      output and consequent hospital stay. LEVEL OF EVIDENCE: Therapeutic Level III.

PMID- 23138238
TI  - Periacetabular osteotomy and combined femoral head-neck junction
      osteochondroplasty: a minimum two-year follow-up cohort study.
AB  - BACKGROUND: Proximal femoral deformities and overcorrection of the acetabulum
      both can result in secondary femoroacetabular impingement and suboptimal clinical
      results after periacetabular osteotomy. The purpose of the present study was to
      determine the rate of complications, the need for reoperations, radiographic
      correction, and hip function among patients who underwent periacetabular
      osteotomy and combined femoral head-neck osteochondroplasty as compared with
      those who underwent periacetabular osteotomy alone. METHODS: Patients who
      underwent periacetabular osteotomy with or without osteochondroplasty of the
      femoral head-neck junction were evaluated retrospectively after a minimum
      duration of follow-up of two years. We compared the two groups with regard to the
      modified Harris hip score, radiographic correction, complications, and
      reoperations. RESULTS: Forty patients (forty hips) who underwent periacetabular
      osteotomy in conjunction with a femoral head-neck osteochondroplasty were
      compared with forty-eight patients (forty-eight hips) who underwent an isolated
      periacetabular osteotomy. Patients were evaluated after a mean duration of follow
      up of 3.4 years (range, 2.0 to 9.7 years). Preoperatively, the modified Harris
      hip score (and standard deviation) was 64.3 +/- 13.2 for the study group and 63.2
      +/- 13.4 for the comparison group. At the time of the latest follow-up, the
      modified Harris hip score was not significantly different between the study group
      and the comparison group (p = 0.17). Patients demonstrated equivalent
      preoperative deformities and postoperative acetabular radiographic parameters.
      There was a significant decrease in the alpha angle and improvement in head-neck
      offset in the study group. There was one reoperation for secondary impingement
      and/or labral pathology in the study group, compared with four reoperations in
      the comparison group. There were no adhesions requiring surgery, femoral neck
      fractures, instances of osteonecrosis, or increases in heterotopic ossification
      in the study group. CONCLUSIONS: Femoral head-neck junction osteochondroplasty
      performed concurrently with a periacetabular osteotomy for the treatment of
      symptomatic acetabular dysplasia and associated femoral head-neck junction
      deformities is not associated with an increased complication rate. This combined
      procedure provides effective correction of associated femoral head-neck
      deformities and produces similar early functional outcomes when compared with
      isolated periacetabular osteotomy. LEVEL OF EVIDENCE: Therapeutic Level III.

PMID- 23138240
TI  - Reverse shoulder arthroplasty for the treatment of rotator cuff deficiency: a
      concise follow-up, at a minimum of five years, of a previous report.
AB  - We previously evaluated ninety-four patients (ninety-six shoulders) who underwent
      reverse shoulder arthroplasty with use of a central compressive screw along with
      5.0-mm peripheral locking screws for baseplate fixation and a center of rotation
      lateral to the glenoid. The purpose of this study was to report updated results
      at a minimum follow-up of five years. Since the last report, an additional two
      patients underwent revision surgery: one for recurrent instability and one for
      resorption of a proximal humeral allograft. The patients continue to have
      improved outcome scores and range of motion. Survivorship with the end point
      being revision for any reason was 73.5 months, with 94% survival at sixty months.
      Radiographic follow-up showed that two (3%) of seventy-six patients included in
      the survivorship analysis had asymptomatic humeral loosening, seven (9%) had
      scapular notching, and no patient had glenoid baseplate loosening or baseplate
      failure. The patients have maintained their improved function with durable
      clinical and radiographic results at a minimum of five years. LEVEL OF EVIDENCE:
      Therapeutic Level IV. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 23138241
TI  - Revision with cementless acetabular components: a concise follow-up, at a minimum
      of twenty years, of previous reports.
AB  - The purpose of the present study was to analyze the longer-term results for a
      previously reported cohort of patients who were managed with cementless
      acetabular fixation at the time of revision arthroplasty. Sixty-one consecutive
      revision total hip arthroplasties were performed in fifty-five patients with use
      of a cementless acetabular component and screw-augmented fixation. This series
      was evaluated at minimum of twenty years. Twelve patients (fourteen hips) were
      living at twenty years. In this group of sixty-one arthroplasties, there were
      nineteen revisions in fourteen hips (22.9%) during the follow-up period, but no
      revisions were performed because of loosening of the acetabular component and no
      additional cups had loosened since the time of the last report at a minimum of
      ten years. Two components had previously been reported as loose and had migrated,
      but neither had been revised at the time of the latest follow-up. The minimum
      twenty-year follow-up of these cementless acetabular components demonstrated
      durable long-term fixation. The survival rate was 100% with revision of the shell
      because of aseptic loosening as the end point and 97.7% (95% confidence interval,
      +/- 8.8%) with radiographic evidence of loosening as the end point. The authors
      continue to use cementless acetabular fixation with screw augmentation for most
      revision total hip arthroplasty procedures. LEVEL OF EVIDENCE: Therapeutic Level
      IV.

PMID- 23138239
TI  - Treatment of articular cartilage defects in the goat with frozen versus fresh
      osteochondral allografts: effects on cartilage stiffness, zonal composition, and
      structure at six months.
AB  - BACKGROUND: Understanding the effectiveness of frozen as compared with fresh
      osteochondral allografts at six months after surgery and the resultant
      consequences of traditional freezing may facilitate in vivo maintenance of
      cartilage integrity. Our hypothesis was that the state of the allograft at
      implantation affects its performance after six months in vivo. METHODS: The
      effect of frozen as compared with fresh storage on in vivo allograft performance
      was determined for osteochondral allografts that were transplanted into seven
      recipient goats and analyzed at six months. Allograft performance was assessed by
      examining osteochondral structure (cartilage thickness, fill, surface location,
      surface degeneration, and bone-cartilage interface location), zonal cartilage
      composition (cellularity, matrix content), and cartilage biomechanical function
      (stiffness). Relationships between cartilage stiffness or cartilage composition
      and surface degeneration were assessed with use of linear regression. RESULTS:
      Fresh allografts maintained cartilage load-bearing function, while also
      maintaining zonal organization of cartilage cellularity and matrix content,
      compared with frozen allografts. Overall, allograft performance was similar
      between fresh allografts and nonoperative controls. However, cartilage stiffness
      was approximately 80% lower (95% confidence interval [CI], 73% to 87%) in the
      frozen allografts than in the nonoperative controls or fresh allografts.
      Concomitantly, in frozen allografts, matrix content and cellularity were
      approximately 55% (95% CI, 22% to 92%) and approximately 96% (95% CI, 94% to 99%)
      lower, respectively, than those in the nonoperative controls and fresh
      allografts. Cartilage stiffness correlated positively with cartilage cellularity
      and matrix content, and negatively with surface degeneration. CONCLUSIONS:
      Maintenance of cartilage load-bearing function in allografts is associated with
      zonal maintenance of cartilage cellularity and matrix content. In this animal
      model, frozen allografts displayed signs of failure at six months, with cartilage
      softening, loss of cells and matrix, and/or graft subsidence, supporting the
      importance of maintaining cell viability during allograft storage and suggesting
      that outcomes at six months may be indicative of long-term (dys)function.
      CLINICAL RELEVANCE: Fresh versus frozen allografts represent the "best versus
      worst" conditions with respect to chondrocyte viability, but "difficult versus
      simple" with respect to acquisition and distribution. The outcomes described from
      these two conditions expand the current understanding of in vivo cartilage
      remodeling and describe structural properties (initial graft subsidence), which
      may have implications for impending graft failure.

PMID- 23138242
TI  - Management of thumb metacarpophalangeal ulnar collateral ligament injuries.
AB  - Untreated ulnar collateral ligament (UCL) injury of the thumb metacarpophalangeal
      joint (MCPJ) can lead to long-term pain and functional limitations.Detection of a
      UCL injury involves sequential examination of true and accessory ligaments and
      comparison with the uninjured side.Acute partial UCL injuries can be successfully
      treated nonoperatively.Acute complete or displaced UCL injuries can be
      successfully treated with operative repair.In cases of chronic UCL injury,
      treatment options include static and dynamic reconstructions.If painful arthrosis
      is present with chronic UCL instability, salvage may be performed with MCPJ
      fusion.

PMID- 23138243
TI  - A biomechanical assessment of soft-tissue damage in the cervical spine following
      a unilateral facet injury.
AB  - BACKGROUND: Unilateral cervical spine facet injuries encompass a wide spectrum,
      including subluxations, dislocations, and fractures, and the instability produced
      varies greatly. The extent of anatomical disruption secondary to a unilateral
      facet injury is poorly understood, and few biomechanical studies have quantified
      the associated kinematics. The purpose of this study was to develop an
      experimental method that reliably produces an impending unilateral facet
      dislocation (perched facet) in cadaveric cervical spines and to identify the soft
      tissue damage and resulting changes in cervical spine range of motion and neutral
      zone associated with this injury. METHODS: Nine fresh-frozen cadaveric human
      spinal motion segments (C4-C5 or C6-C7) were mounted in a spinal loading
      simulator to induce a perched unilateral facet injury based on a previously
      described mechanism of flexion and bending with increasing rotation. Loads were
      applied to simulate and measure flexion-extension, lateral bending, and axial
      rotation motions before and after achieving a perched facet. Preinjury and
      postinjury range of motion and neutral zone were analyzed with use of paired t
      tests for each movement. Systematic qualitative inspection and gross dissection
      were then performed to define the soft-tissue injury pattern. RESULTS: Range of
      motion and neutral zone increased following the reduction of this injury; the
      largest increase (294%) occurred in contralateral axial rotation (i.e., right
      axial rotation after a perched left facet). Postinjury dissections revealed
      bilateral capsular tears, 50% disc disruption, and 50% tearing of the ligamentum
      flavum in most specimens. The interspinous and supraspinous ligaments were
      stretched in less than half of the specimens and were never completely disrupted.
      The longitudinal ligaments were occasionally torn as extensions of anulus
      fibrosus disruptions. CONCLUSIONS: This study indicates that the anulus fibrosus,
      nucleus pulposus, and ligamentum flavum are important cervical spine stabilizers.
      Facet capsules were often torn bilaterally, implying a more advanced injury than
      a unilateral facet injury. These discoligamentous injuries result in increases in
      range of motion and neutral zone. CLINICAL RELEVANCE: The results from this work
      provide further insight into the expected injury and associated instability
      present in a traumatic unilateral facet injury in the cervical spine.

PMID- 23138244
TI  - Calcific periarthritis: more than a shoulder problem: a series of fifteen cases.
AB  - BACKGROUND: Calcific periarthritis, referring to a circumscribed juxta-articular
      deposit of minute non-birefringent mineral grains, is rarely the clinical
      diagnosis accompanying a pathologic specimen. Familiarity with the clinical,
      pathologic, and radiologic manifestations of calcific periarthritis, particularly
      when encountered adjacent to joints other than the shoulder, facilitates
      diagnosis and may obviate biopsy, avoid confusion with other entities, and speed
      appropriate treatment. METHODS: Pathologic specimens that fulfilled the criteria
      for a diagnosis of calcific periarthritis were prospectively collected. Clinical
      history and radiologic studies were acquired and analyzed. Well-controlled
      special stains were employed on two specimens with a neutrophilic infiltrate that
      excluded fungal and bacterial agents, as corroborated by microbiologic cultures
      showing no growth. RESULTS: Over a five-year period, fifteen patients between the
      ages of thirty-one and eighty-eight years (mean age, fifty-nine years) presented
      to various local healthcare providers for treatment of juxta-articular swelling
      that was subsequently determined to be calcific periarthritis. In seven patients,
      deposits were alongside a toe joint; in five, alongside a finger joint; and in
      three, involving the shoulder. The majority of the patients were female (73%). No
      patient had a documented recurrence of calcific periarthritis in follow-up
      periods ranging from eighteen to eighty-seven months (average forty-five months).
      CONCLUSIONS: Of twelve histologically verified cases of calcific periarthritis
      adjacent to joints other than the shoulder, in only one patient (toe) was the
      preoperative clinical diagnosis accurate, which signals the need for greater
      awareness of this entity as a differential diagnostic option.

PMID- 23138245
TI  - Graduated introduction of orthopaedic implants: encouraging innovation and
      minimizing harm.
AB  - There is continued pressure for the development of innovative orthopaedic
      surgical devices and techniques to meet the demands of increasingly younger and
      more active patients. However, as demonstrated by several recent orthopaedic
      implant withdrawals and recalls, clinically important unknown modes of failure
      for newly introduced devices may not become apparent for several years after
      widespread adoption, affecting a large number of patients. Different reasons have
      been implicated for this problem, including weaknesses in the United States
      medical device approval process, as well as deficiencies in mechanisms for post
      approval implant performance monitoring. Several remedies have been proposed over
      the past decades. We aim to stimulate discussion concerning the adoption of
      orthopaedic technology by describing the concept of a graduated implant approval
      process for orthopaedic devices that builds on recommendations previously made by
      other authors; by explaining how this will benefit patients, surgeons, and device
      manufacturers; and by clarifying why the time has come for the orthopaedic
      community to reconsider the adoption of such a process.

PMID- 23138246
TI  - Resident education versus fellowship training-conflict or synergy? AOA critical
      issues.

PMID- 23138247
TI  - Shoulder arthroscopy simulator performance correlates with resident and shoulder
      arthroscopy experience.
AB  - BACKGROUND: The technical skills required to perform arthroscopy are multifaceted
      and require supervised training and repetition. Obtaining this basic arthroscopic
      skill set can be costly and time-consuming. Simulation may represent a viable
      training source for basic arthroscopic skills. Our goal was to evaluate the
      correlation between timed task performance on an arthroscopic shoulder simulator
      and both resident experience and shoulder arthroscopy experience. METHODS: Twenty
      seven residents were voluntarily recruited from an orthopaedic residency program.
      Each subject was tested annually for three consecutive years on an arthroscopic
      shoulder simulator and objectively scored on time to completion of a standardized
      object localization task. Each subject's total number of shoulder arthroscopies,
      all arthroscopies, and cases were calculated according to postgraduate year from
      their Accreditation Council for Graduate Medical Education (ACGME) case log.
      Generalized estimating equation multivariate regression analysis was performed to
      determine the correlation between simulation performance and total numbers of
      shoulder arthroscopies, all arthroscopies, and cases. RESULTS: Univariate
      analyses revealed that postgraduate year, total number of shoulder arthroscopies,
      total number of arthroscopies of any joint, and total number of surgical cases
      performed during residency training prior to testing were associated with the
      mean time required to complete the simulator task. The number of prior shoulder
      arthroscopies performed (r = 0.55) and postgraduate year in training (r = 0.60)
      correlated most strongly with simulator basic task performance. In the
      multivariate analysis, the number of prior shoulder arthroscopies and
      postgraduate year remained independent predictors of faster completion of the
      simulator task. For every additional postgraduate year, there was a sixteen
      second improvement in the time required to complete the simulator task (p <
      0.005). Similarly, after controlling for the influence of postgraduate year,
      there was a twelve-second decrease in the time to complete the simulator task for
      every additional fifty shoulder arthroscopies performed during residency training
      (p < 0.008). CONCLUSIONS: These results showed a significant relationship between
      performance of basic arthroscopic tasks in a simulator model and the number of
      shoulder arthroscopies performed. The data confirmed our hypothesis that
      simulator performance is representative of both resident experience and shoulder
      arthroscopy experience. CLINICAL RELEVANCE: This study suggests that greater
      resident clinical experience and shoulder arthroscopy experience are both
      reflected in improved performance of basic tasks on a shoulder simulator. These
      findings warrant further investigation to determine if training on a validated
      arthroscopic shoulder simulator would improve clinical arthroscopic skills.

PMID- 23138248
TI  - Twist and turn: commentary on an article by Robert S. Namba, MD, et al.: "risk of
      revision for fixed versus mobile-bearing primary total knee replacements".

PMID- 23138249
TI  - Oxidation of frying oils during intermittent usage.
AB  - We reported previously that in oils used for frying by commercial establishments,
      a high correlation was observed among their Gardner colors, polar compound
      contents (PC), carbonyl values (CV) and acid values (AV). However, this was not
      true for frying oils used in hospitals. In the present study, oils that had been
      used for deep-frying in hospital kitchens were collected and assayed for PC, CV,
      AV, and Gardner color value to determine the reason for the differences from oil
      used in commercial establishments. Hospitals were selected so that variation in
      the number of inpatients, frying oil fatty acid composition, and frying frequency
      was obtained. As previously observed, we did not find good correlations between
      the color of the frying oil and the PC, CV or AV, respectively. The extent of
      oxidation in batches of oil repeatedly used for deep-frying was in the following
      order: soybean oil > blended oil > canola oil. After use in deep-frying, where
      the oxygen content goes effectively to zero, allowing the oil to stand at room
      temperature resulted in the quick and steady absorption of oxygen until it
      returned to its initial content. In addition to the effect of thermal treatment
      of oil, standing time between usages is a significantt cause of oxidation.

PMID- 23138250
TI  - Chemoenzymatic synthesis and properties of novel lactone-type anionic
      surfactants.
AB  - Two series of lactone-type surfactants with and without a hexyl side chain were
      prepared by the cyclocondensation of dimethyl alkanedioates with unsaturated
      diols, such as cis-2-butene-1,4-diol and ricinoleyl alcohol, using a lipase,
      followed by the addition of hydrophilic 3-mercaptopropionic acid in the presence
      of triethylamine. The lactone-type surfactants showed clear cmc values and
      surface tension lowering in aqueous solution irrespective of the hexyl side
      chain. It was found that the cmc values of lactone-type surfactants were lower
      than that of typical anionics, e.g., sodium laurate, and the cmc value became
      lower with increasing size of the lactone ring. The adsorption area at the
      surface of the aqueous lactone-type surfactant solution was larger when compared
      to the corresponding non-lactone-type surfactants. Lactone-type surfactants
      without the hexyl side chain aggregated quickly, forming 3-10 nm micelles; on the
      other hand, lactone-type surfactants with the hexyl side chain formed
      significantly larger micelles. This is due to the steric hindrance of the hexyl
      group on the lactone ring. The solubilization ability of the lactone-type
      surfactants with a hexyl side chain was superior to those without a hexyl side
      chain. The lactone-type surfactants showed a high foaming power and low foaming
      stability. They were also biodegraded by activated sludge.

PMID- 23138251
TI  - Petroleum-collecting and dispersing complexes based on oleic acid and nitrogenous
      compounds as surface-active agents for removing thin petroleum films from water
      surface.
AB  - Petroleum-collecting and dispersing complexes were synthesized on the basis of
      oleic acid and nitrogen-containing compounds. Surface-active properties
      (interfacial tension) of the obtained complexes were investigated by
      stalagmometric method. Petroleum-collecting and dispersing properties of the
      oleic acid complexes in diluted (5% wt. water or alcoholic solution) and
      undiluted form have been studied in waters of varying salinity (distilled, fresh
      and sea waters). Some of physico-chemical indices of the prepared compounds such
      as solubility, acid and amine numbers as well as electrical conductivity have
      been determined. The ability of oleic acid complex with ethylenediamine as petro
      collecting and dispersing agent towards different types of petroleum has been
      studied. The influence of thickness and "age" of the petroleum slick on
      collecting and dispersing capacity of this complex has been clarified. Surface
      properties studied included critical micelle concentration (CMC), maximum surface
      excess (Gamma(max)), and minimum surface area (A(min)). Free energies of
      micellization (DeltaG degrees (mic)) and adsorption (DeltaG degrees (ads)) were
      calculated.

PMID- 23138252
TI  - Synthesis of carboxylic acids, esters, alcohols and ethers containing a
      tetrahydropyran ring derived from 6-methyl-5-hepten-2-one.
AB  - 3-hydroxy acids, 3-hydroxy-3,7-dimethyloct-6-enoic acid (1) and 3-hydroxy-2,2,3,7
      tetramethyloct-6-enoic acid (2), were prepared from 6-methyl-5-hepten-2-one, and
      they were subsequently used to prepare (2,6,6-trimethyltetrahydropyran-2
      yl)acetic acid (3) and 2-methyl-2-(2,6,6-trimethyltetrahydropyran-2-yl)propanoic
      acid (4), respectively, via cyclization with an acidic catalyst such as boron
      trifluoride diethyl etherate or iodine. The reaction of carboxylic acids 3 and 4
      with alcohols, including methanol, ethanol, and 1-propanol, produced the
      corresponding methyl, ethyl, and propyl esters, which all contained a
      tetrahydropyran ring. Reduction of carboxylic acids 3 and 4 afforded the
      corresponding alcohols. Subsequent reactions of these alcohols with several acyl
      chlorides produced novel esters. The alcohols also reacted with methyl iodide and
      sodium hydride to provide novel ethers. A one-pot cyclization-esterification of 1
      to produce esters containing a tetrahydropyran ring, using iodine as a catalyst,
      was also investigated.

PMID- 23138253
TI  - Antioxidant and antimicrobial activities of clove bud essential oil and eugenol
      nanoparticles in alcohol-free microemulsion.
AB  - Clove bud essential oil (CEO) and its major individual phenolic constituent
      eugenol were formulated as nanoparticles in water-based microemulsion systems.
      The oil titration method was used to incorporate different amounts of the oil and
      eugenol in the micellar solution of Tween-20. The Antioxidant and antimicrobial
      activities were evaluated using the DPPH* free radical scavenging assay and the
      agar disc dilution method, respectively. Results showed that microemulsion
      improved the evaluated activities of CEO and eugenol compared with the crude
      counterparts. Individual eugenol microemulsion was more effective than CEO
      microemulsion which contained only 61.7% eugenol among its constituents.  The
      results of this study could have potential applications in water-based
      disinfectants, preservation and flavoring of food and in personal hygiene
      products. It may also have promising applications in the nutraceutical and
      functional beverage field.

PMID- 23138254
TI  - Dynamic molecular behavior of semi-fluorinated oleic, elaidic and stearic acids
      in the liquid state.
AB  - Ordinary fatty acids such as oleic, elaidic and stearic acids exist as their
      hydrogen-bonded dimers in their liquids and in non-polar solvents. Infrared (IR)
      and nuclear magnetic resonance (NMR) spectroscopy have revealed that semi
      fluorinated (SF) acids containing a perfluorooctyl group (C8F17) as a terminal
      segment exist also as hydrogen-bonded dimers, which are the units of inter- and
      intramolecular movements in their liquids and CCl4. The dynamic molecular
      properties, such as self-diffusion coefficients and intramolecular movements of
      SF-oleic, SF-elaidic, and SF-stearic acids were compared with those of
      corresponding ordinary fatty acids (H-acids). From the high equilibrium spreading
      pressures (ESPs) for SF-acids compared with those for their corresponding H
      acids, it was expected that the inter-acyl chain interaction is weaker for the SF
      acid than for the H-acid: the SF-fatty acids should have higher molecular
      mobility than the corresponding ordinary H-acids in the liquid state. However,
      the self-diffusion coefficients obtained for SF-acids were smaller than those for
      the corresponding H-acids; the apparent activation energies for the self
      diffusion process (translational movement) of SF-acids were larger than those for
      the corresponding H-acids. Namely, the motion of SF-acid molecules in a liquid
      phase is rather restricted compared with H-acid in spite of lower inter-acyl
      chain interaction of SF-acid. This unexpected result suggests that the molecular
      motion of SF-acid in a liquid phase is not directly governed by inter-acyl
      interaction, but may be interpreted as a reptation movement of an acid molecule,
      which is related to intramolecular movement. In fact, low intramolecular
      movements for SF-acid were confirmed by 13C-NMR T1 measurements.

PMID- 23138255
TI  - Low molecular weight gelators based on biosurfactants, cellobiose lipids by
      Cryptococcus humicola.
AB  - Cellobiose lipids (CLs) are bolaform glycolipid biosurfactants, which are
      produced from natural resources by a yeast strain and show fungicidal activity.
      In this study, the gelation properties of CL in solvents were investigated by
      several techniques including rheology and atomic force microscopy (AFM). The
      yeast CL was found to gelate 6 out of 26 solvents. Although it did not provide
      gels in ethanol or 1, 3-butanediol which are widely used for cosmetic industries,
      we succeeded in producing gels by mixing ethanol or 1, 3-butanediol with water.
      AFM observation of the gels on a silicon substrate provided 3D supramolecular
      structures with an entangled fibrous network. Moreover, it was also found that
      some of fibrous structures were twisted helical ribbons. This should be due to
      the cellobiose backbone having several chiral functional groups. The sol-gel
      phase transition temperatures for gels in mixed ethanol/water and 1, 3
      butanediol/water systems were below 100 degrees C, indicating that the gels can
      be obtained with rather mild preparation conditions. The present CL gels would be
      useful for novel multifunctional materials applicable to various industries.

PMID- 23138256
TI  - Sodium aluminate as catalyst for transesterification of waste mutton fat.
AB  - Sodium aluminate and its calcinied forms have been evaluated as basic catalysts
      for the transesterification of waste mutton fat with methanol. The decrease in
      catalytic activity has been observed with calcinied sodium alumiate. Fat and
      methanol in 1:29 molar ratio with 1.5 wt.% of sodium aluminate under reflux
      resulted in 97 % conversion to biodiesel in 1h 20 min. The reaction showed
      tolerance of additional moisture content of 1 wt.%.

PMID- 23138257
TI  - Cardiac arrest in the operating room: do we need to check the carotid pulse?

PMID- 23138259
TI  - Comparison of multidirectional seated postural stability between individuals with
      spinal cord injury and able-bodied individuals.
AB  - OBJECTIVES: To compare multidirectional seated postural stability between
      individuals with spinal cord injury and able-bodied- individuals and to evaluate
      the impact of abdominal and low back muscle paralysis on multidirectional seated
      stability. DESIGN: Case-control study. PARTICIPANTS: Fifteen individuals with
      complete or incomplete spinal cord injury affecting various vertebral levels
      participated in this study and were gender-matched with 15 able-bodied
      individuals. METHODS: Participants were instructed to lean as far as possible in
      8 directions, set apart by 45 degrees  intervals, while seated on an instrumented
      chair with their feet placed on force plates. Eight direction-specific stability
      indices and a global stability index were calculated. RESULTS: The global
      stability index and all direction-specific indices, except in the anterior and
      posterior directions, were lower in individuals with spinal cord injury than in
      able-bodied individuals. However, the individuals with spinal cord injury who had
      partial or full control of their abdominal and lower trunk muscles obtained a
      similar global stability index and similar direction-specific indices compared to
      the able-bodied individuals. CONCLUSION: Multidirectional seated postural
      stability is reduced in individuals with SCI who have paralysis of the abdominal
      and lower back muscles in comparison to able-bodied individuals.

PMID- 23138258
TI  - Clinical outcomes and natural history of pediatric brainstem tumors: with 33
      cases follow-ups.
AB  - The purpose of this study is to investigate the patient characteristics and
      clinical outcomes of children with pediatric brainstem glioma. Between 2004 and
      2009, a total of 42 children were diagnosed with brainstem gliomas at the
      Neurosurgical Center of Beijing Tiantan Hospital, China. A retrospective study
      including the 33 patients of this cohort with complete follow-up was conducted in
      an attempt to better understand clinical outcomes following multidisciplinary
      treatment modalities for pediatric brainstem gliomas. Investigational variables
      including clinical presentations, anatomical distribution, radiological findings,
      and clinical outcomes were analyzed. Survival time difference was computed using
      a Kaplan-Meier method with a log-rank test between groups. The Cox proportional
      hazards regression model was utilized in the multivariate analysis to determine
      the independent prognostic factors. Overall median survival of the entire series
      of patients was 11 months with a 1-year actuarial survival rate of 43.6 %. In
      nine patients who received no treatment after diagnosis, all patients expired
      within 8 months with a median time of 3.5 months. On univariate analysis, the
      following variables including older age at diagnosis, higher Karnofsky
      Performance Status score at diagnosis, the lower pathological grade, surgical
      resection modality, increasing diagnostic latency, and focal growth pattern were
      associated with better survival. On multivariate analysis, only the last two
      variables were associated with survival advantage. Focal pediatric brainstem
      gliomas amenable to a surgical resection are likely to achieve a prolonged
      survival. Clinical trials on larger number of patients are of importance in
      further understanding this spectrum of devastating diseases.

PMID- 23138260
TI  - Letter to the editor: Is there really no benefit of vertebroplasty for
      osteoporotic vertebral fractures? A meta-analysis.

PMID- 23138261
TI  - Exploration of optimal dosing regimens of haloperidol, a D2 Antagonist, via
      modeling and simulation analysis in a D2 receptor occupancy study.
AB  - PURPOSE: To evaluate the potential usage of D(2) receptor occupancy (D2RO)
      measured by positron emission tomography (PET) in antipsychotic development.
      METHODS: In this randomized, parallel group study, eight healthy male volunteers
      received oral doses of 0.5 (n = 3), 1 (n = 2), or 3 mg (n = 3) of haloperidol
      once daily for 7 days. PET's were scanned before haloperidol, and on days 8, 12,
      with serial pharmacokinetic sampling on day 7. Pharmacokinetics and binding
      potential to D(2) receptor in putamen and caudate nucleus over time were analyzed
      using NONMEM, and simulations for the profiles of D2RO over time on various
      regimens of haloperidol were conducted to find the optimal dosing regimens.
      RESULTS: One compartment model with a saturable binding compartment, and
      inhibitory E(max) model in the effect compartment best described the data. Plasma
      haloperidol concentrations at half-maximal inhibition were 0.791 and 0.650 ng/ml,
      in putamen and caudate nucleus. Simulation suggested haloperidol 2 mg every 12 h
      is near the optimal dose. CONCLUSION: This study showed that sparse D2RO
      measurements in steady state pharmacodynamic design after multiple dosing could
      reveal the possibility of treatment effect of D(2) antagonist, and could identify
      the potential optimal doses for later clinical studies by modeling and
      simulation.

PMID- 23138262
TI  - Skin permeation of small-molecule drugs, macromolecules, and nanoparticles
      mediated by a fractional carbon dioxide laser: the role of hair follicles.
AB  - PURPOSE: To evaluate skin permeation enhancement mediated by fractional laser for
      different permeants, including hydroquinone, imiquimod, fluorescein
      isothiocyanate-labeled dextran (FD), and quantum dots. METHODS: Skin received a
      single irradiation of a fractional CO(2) laser, using fluence of 2 or 4 mJ with
      densities of 100 ~ 400 spots/cm(2). In vitro and in vivo skin penetration
      experiments were performed. Fluorescence and confocal microscopies for imaging
      delivery pathways were used. RESULTS: The laser enhanced flux of small-molecule
      drugs 2 ~ 5-fold compared to intact skin. A laser fluence of 4 mJ with a 400
      spot/cm(2) density promoted FD flux at 20 and 40 kDa from 0 (passive transport)
      to 0.72 and 0.43 nmol/cm(2)/h, respectively. Microscopic images demonstrated a
      significant increase in fluorescence accumulation and penetration depth of
      macromolecules and nanoparticles after laser exposure. Predominant routes for
      laser-assisted delivery may be intercellular and follicular transport. CO(2)
      laser irradiation produced 13-fold enhancement in follicular deposition of
      imiquimod. Laser-mediated follicular transport could deliver permeants to deeper
      strata. Skin barrier function as determined by transepidermal water loss
      completely recovered by 12 h after irradiation, much faster than conventional
      laser treatment (4 days). CONCLUSIONS: Fractional laser could selectively enhance
      permeant targeting to follicles such as imiquimod and FD but not hydroquinone,
      indicating the importance of selecting feasible drugs for laser-assisted follicle
      delivery.

PMID- 23138264
TI  - Zn(II), Cd(II) and Cu(II) complexes of 2,5-bis{N-(2,6
      diisopropylphenyl)iminomethyl}pyrrole: synthesis, structures and their high
      catalytic activity for efficient cyclic carbonate synthesis.
AB  - The syntheses of Zn(II), Cd(II) and Cu(II) complexes of 2,5-bis{N-(2,6
      diisopropylphenyl)iminomethyl}pyrrole (DIP(2)pyr)H 1 and their catalytic
      activities in CO(2) fixation are reported. The structures of these complexes were
      characterized by IR, (1)H, (13)C NMR and single crystal X-ray diffraction
      techniques. The catalytic activities of these complexes for the cycloaddition of
      CO(2) to an epoxide under one atmosphere of pressure and mild temperature
      conditions to yield cyclic carbonate have been studied. Among the four complexes
      synthesized, the Zn(II) and Cu(II) complexes were found to be versatile whereas
      the Cu(II) complex was more selective in the conversion. They were highly
      effective for the conversion of monosubstituted terminal epoxides, disubstituted
      terminal and internal epoxides to their corresponding cyclic carbonates with good
      to high yields.

PMID- 23138263
TI  - Rapid insight into heating-induced phase transformations in the solid state of
      the calcium salt of atorvastatin using multivariate data analysis.
AB  - PURPOSE: To investigate the heating-induced dehydration and melting behavior of
      the trihydrate phase of the calcium salt of atorvastatin. METHODS: Multivariate
      curve resolution (MCR) was used to decompose a variable-temperature synchrotron X
      ray powder diffraction (VT-XRPD) data matrix into diffraction patterns and
      concentration profiles of pure drug phases. RESULTS: By means of the MCR
      estimated diffraction patterns and concentration profiles, the trihydrate phase
      of the drug salt was found to dehydrate sequentially into two partially
      dehydrated hydrate structures upon heating from 25 to 110 degrees C, with no
      associated breakage of the original crystal lattice. During heating from 110 to
      140 degrees C, the remaining water was lost from the solid drug salt, which
      instantly collapsed into a liquid crystalline phase. An isotropic melt was formed
      above 155 degrees C. Thermogravimetric analysis, hot-stage polarized light
      microscopy, and hot-stage Raman spectroscopy combined with principal component
      analysis (PCA) was shown to provide consistent results. CONCLUSIONS: This study
      demonstrates that MCR combined with VT-XRPD is a powerful tool for rapid
      interpretation of complex dehydration behavior of drug hydrates, and it is also
      the first report on a liquid crystalline phase of the calcium salt of
      atorvastatin.

PMID- 23138265
TI  - Three cases of IgG4-related orbital inflammation presented as unilateral
      pseudotumor and review of the literature.
AB  - IgG4-related disease is an emerging disease entity characterized by elevated
      serum IgG4 concentration and tumefaction or tissue infiltration by IgG4-positive
      plasma cells. In IgG4-related disease, tumor-like lesions develop in multiple
      organs, such as the lacrimal gland, salivary gland, lung, pancreas, kidney, and
      lymph nodes. We report here three cases of IgG4-related orbital inflammation that
      presented as unilateral pseudotumors. The patients all were men, with an age
      range of 65-75 years. The patients had been pointed out unilateral intra-orbital
      masses, and histopathological examinations revealed marked accumulation of IgG4
      positive plasma cells (IgG4/IgG ratio: 51.1-71.6%) with fibrosis. But storiform
      fibrosis was seen in only one case, and no obliterative phlebitis was seen. The
      serum levels of IgG4 were increased to 178-670 mg/dL. The masses had well-defined
      homogeneous signal intensities, and they were hypo-intense on T1-weighted MR
      images and iso-intense on T2-weighted MR images. Gadolinium enhanced mass lesions
      in two cases. All orbital mass lesions responded well to corticosteroid
      treatment.

PMID- 23138266
TI  - De novo prediction of RNA-protein interactions from sequence information.
AB  - Protein-RNA interactions are fundamentally important in understanding cellular
      processes. In particular, non-coding RNA-protein interactions play an important
      role to facilitate biological functions in signalling, transcriptional
      regulation, and even the progression of complex diseases. However, experimental
      determination of protein-RNA interactions remains time-consuming and labour
      intensive. Here, we develop a novel extended naive-Bayes-classifier for de novo
      prediction of protein-RNA interactions, only using protein and RNA sequence
      information. Specifically, we first collect a set of known protein-RNA
      interactions as gold-standard positives and extract sequence-based features to
      represent each protein-RNA pair. To fill the gap between high dimensional
      features and scarcity of gold-standard positives, we select effective features by
      cutting a likelihood ratio score, which not only reduces the computational
      complexity but also allows transparent feature integration during prediction. An
      extended naive Bayes classifier is then constructed using these effective
      features to train a protein-RNA interaction prediction model. Numerical
      experiments show that our method can achieve the prediction accuracy of 0.77 even
      though only a small number of protein-RNA interaction data are available. In
      particular, we demonstrate that the extended naive-Bayes-classifier is superior
      to the naive-Bayes-classifier by fully considering the dependences among
      features. Importantly, we conduct ncRNA pull-down experiments to validate the
      predicted novel protein-RNA interactions and identify the interacting proteins of
      sbRNA CeN72 in C. elegans, which further demonstrates the effectiveness of our
      method.

PMID- 23138267
TI  - alpha-Linolenic acid suppresses cholesterol and triacylglycerol biosynthesis
      pathway by suppressing SREBP-2, SREBP-1a and -1c expression.
AB  - alpha-Linolenic acid (ALA), a major fatty acid in flaxseed oil, has multiple
      functionalities such as anti-cardiovascular and anti-hypertensive activities. In
      this study, we investigated the effects of ALA on lipid metabolism and studied
      the possible mechanisms of its action in differentiated 3T3-L1 adipocytes using
      DNA microarray analysis. From a total of 34,325 genes in the DNA chip, 87 genes
      were down-regulated and 185 genes were up-regulated at least twofold in
      differentiated 3T3-L1 adipocyte cells treated with 300 MUM ALA for a week, 5-12
      days after induction of cell differentiation, compared to ALA-untreated 3T3-L1
      adipocytes (control). From the Reactome analysis results, eight lipid metabolism
      related genes involved in cholesterol and triacylglycerol biosynthesis pathway
      and lipid transport were significantly down-regulated by ALA treatment.
      Furthermore, ALA significantly decreased the mRNA expressions of sterol
      regulatory element binding protein (SREBP)-2, SREBP-1a, SREBP-1c and fatty acid
      synthase (FAS) in 3T3-L1 adipocyte cells. On the other hand, the average levels
      of the gene expressions of carnitine palmitoyltransferase 1a (CPT-1a) and leptin
      in 300 MUM ALA treatment were increased by 1.7- and 2.9-fold, respectively,
      followed by an increase in the intracellular ATP content. These results show that
      ALA is likely to inhibit cholesterol and fatty acid biosynthesis pathway by
      suppressing the expression of transcriptional factor SREBPs. Furthermore, ALA
      promotes fatty acid oxidation in 3T3-L1 adipocytes, thereby increasing its health
      benefits. 

PMID- 23138269
TI  - InP nanocrystals on silicon for optoelectronic applications.
AB  - One of the solutions enabling performance progress, which can overcome the
      downsizing limit in silicon technology, is the integration of different
      functional optoelectronic devices within a single chip. Silicon with its indirect
      band gap has poor optical properties, which is its main drawback. Therefore, a
      different material has to be used for the on-chip optical interconnections, e.g.
      a direct band gap III-V compound semiconductor material. In the paper we present
      the synthesis of single crystalline InP nanodots (NDs) on silicon using combined
      ion implantation and millisecond flash lamp annealing techniques. The optical and
      microstructural investigations reveal the growth of high-quality (100)-oriented
      InP nanocrystals. The current-voltage measurements confirm the formation of an n
      p heterojunction between the InP NDs and silicon. The main advantage of our
      method is its integration with large-scale silicon technology, which allows
      applying it for Si-based optoelectronic devices.

PMID- 23138268
TI  - A mechanistic model for the light response of photosynthetic electron transport
      rate based on light harvesting properties of photosynthetic pigment molecules.
AB  - Models describing the light response of photosynthetic electron transport rate
      (ETR) are routinely used to determine how light absorption influences energy,
      reducing power and yields of primary productivity; however, no single model is
      currently able to provide insight into the fundamental processes that implicitly
      govern the variability of light absorption. Here we present development and
      application of a new mechanistic model of ETR for photosystem II based on the
      light harvesting (absorption and transfer to the core 'reaction centres')
      characteristics of photosynthetic pigment molecules. Within this model a series
      of equations are used to describe novel biophysical and biochemical
      characteristics of photosynthetic pigment molecules and in turn light harvesting;
      specifically, the eigen-absorption cross-section and the minimum average lifetime
      of photosynthetic pigment molecules in the excited state, which describe the
      ability of light absorption of photosynthetic pigment molecules and retention
      time of excitons in the excited state but are difficult to be measured directly.
      We applied this model to a series of previously collected fluorescence data and
      demonstrated that our model described well the light response curves of ETR,
      regardless of whether dynamic down-regulation of PSII occurs, for a range of
      photosynthetic organisms (Abies alba, Picea abies, Pinus mugo and Emiliania
      huxleyi). Inherent estimated parameters (e.g. maximum ETR and the saturation
      irradiance) by our model are in very close agreement with the measured data.
      Overall, our mechanistic model potentially provides novel insights into the
      regulation of ETR by light harvesting properties as well as dynamical down
      regulation of PSII.

PMID- 23138270
TI  - MYH rs3219476 and rs3219472 polymorphisms and risk of cholangiocarcinoma.
AB  - Cholangiocarcinoma (CCA) is a rare but devastating malignancy. Up to 90% of
      patients presenting with CCA have no identifiable risk factors. The base excision
      repair (BER) pathway has a principal role in the repair of mutations caused by
      oxidized or reduced bases. The MutY homolog (MUTYH, MYH) is one of the key
      proteins in the BER pathway, but the role of MYH in the tumorigenesis of CCA is
      largely unknown. In this study, we investigated the influence of MYH rs3219476
      and rs3219472 polymorphisms on CCA incidence. MYH genotypes were detected using a
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      technique. We found that for rs3219472, compared with subjects carrying the MYH
      G/G genotype, those with the A/A genotype had a 2.816-fold higher risk of CCA
      [odds ratio (OR)=2.816, 95% confidence interval (CI)=0.992-7.999, P=0.047). For
      rs3219476, compared with subjects carrying the MYH T/T genotype, those with the
      T/G genotype had a reduced risk of CCA (OR=0.359, 95% CI=0.17-0.758, P=0.006).
      Our findings suggest that since significantly increased CCA risk was found in
      individuals with a homozygous variant genotype for rs3219472, it may be a
      biomarker for screening individuals at high risk of developing the disease. 

PMID- 23138271
TI  - Drug-induced interstitial lung disease in molecular targeted therapies: high
      resolution CT findings.
AB  - Drug-induced lung injury (DLI) comprises a wide variety of pathologies, each with
      a unique imaging pattern, so there are no characteristic imaging findings to
      establish diagnosis. When DLI is suspected, evaluation must exclude progression
      of underlying disease, infection, and mimicking diseases. Correct diagnosis
      requires integration of clinical information and radiologic, laboratory, and
      pathological findings when available. We describe the radiologic findings of DLI,
      the roles of the findings in the management of patients with DLI, and the
      limitations of radiologic diagnosis.

PMID- 23138272
TI  - A systematic review of the nutritional status of women of a childbearing age with
      severe mental illness.
AB  - Little is known about the nutritional status of pregnant women with severe mental
      illness. We therefore carried out a systematic review to investigate whether
      pregnant women and childbearing aged women with severe mental illness have
      significantly greater nutritional deficiencies compared with pregnant women and
      childbearing aged women with no mental illness. We carried out a search using
      MEDLINE, EMBASE and PsycINFO from January 1980 to January 2011 for studies on
      nutritional status of childbearing aged women with psychotic disorders.
      Identification of papers and quality rating of papers (using a modified version
      of the Newcastle-Ottawa scale) was carried out by two reviewers independently. We
      identified and screened 4,130 potentially relevant studies from the electronic
      databases. Fifteen studies met the inclusion criteria (n = 587 women). There were
      no studies of pregnant women. There was some evidence of low serum folate and
      vitamin B(12) levels and elevated homocysteine levels in childbearing aged women
      with psychotic disorders. Further research into the nutritional status of
      childbearing aged women with severe mental illness is needed. Maternal nutrition
      has a profound impact on foetal outcome, is a modifiable risk factor and
      therefore needs prioritising in the care of all childbearing aged women with
      severe mental illness.

PMID- 23138274
TI  - Knocking on the clinic door.

PMID- 23138273
TI  - Less depressed or less forthcoming? Self-report of depression symptoms in women
      preparing for in vitro fertilization.
AB  - While depression has been associated with infertility treatments, it is not
      routinely assessed in women prior to undergoing in vitro fertilization (IVF)
      treatment. Findings are mixed regarding the degree to which women report
      depression prior to IVF. The purpose of this study was to (1) examine response
      profiles in women preparing for IVF and (2) compare responses to those of
      postpartum, primary care, and general population groups. Female IVF patients (n =
      321; 19-45 years) completed the Patient Health Questionnaire-9 (PHQ-9) at their
      first visit. Clinical and demographic characteristics and incidence of major
      depressive disorder (MDD) and other depressive disorders (ODD) were examined.
      Overall score distributions of the IVF group were compared to those of local
      postpartum patients and published primary care and general populations.
      Demographic or clinical characteristics did not account for response differences
      within the IVF group. The IVF group had lower incidences of MDD and ODD than a
      PHQ-9 normative group. Women in the IVF group reported no depressive symptoms
      significantly more than postpartum, primary care, and general population groups.
      Women preparing to undergo IVF report fewer symptoms of depression than multiple
      comparison groups. Specific quality of life measures may be needed to assess
      distress in this population.

PMID- 23138275
TI  - Next-generation proteasome inhibitor approved in multiple myeloma.

PMID- 23138277
TI  - Miniature wireless sensors presage smart phone medicine.

PMID- 23138280
TI  - Calamitous HCV trial casts shadow over nucleoside drugs.

PMID- 23138281
TI  - Deals center on self-reported patient data services.

PMID- 23138282
TI  - GM phobia spreads in South Asia.

PMID- 23138284
TI  - Media leaps on French study claiming GM maize carcinogenicity.

PMID- 23138286
TI  - Opposition thaws for GM crops in Africa.

PMID- 23138287
TI  - Biotech crowdfunding paves way for angels.

PMID- 23138288
TI  - The New York Genome Center.

PMID- 23138289
TI  - The battle for sequencing supremacy.

PMID- 23138290
TI  - Direct-to-consumer genomics reinvents itself.

PMID- 23138291
TI  - Stranger in a strange land?

PMID- 23138292
TI  - Assuring the quality of next-generation sequencing in clinical laboratory
      practice.

PMID- 23138293
TI  - NGS analyses by visualization with Trackster.

PMID- 23138294
TI  - Proteomics-directed cloning of circulating antiviral human monoclonal antibodies.

PMID- 23138295
TI  - Analyzing the association of SCNA boundaries with replication timing.

PMID- 23138297
TI  - DNA goes to court.

PMID- 23138298
TI  - Advances in DNA sequencing lead to patent disputes.

PMID- 23138300
TI  - Insulating gene circuits from context by RNA processing.

PMID- 23138301
TI  - Single-stranded siRNAs for in vivo gene silencing.

PMID- 23138302
TI  - The implications of ENCODE for diagnostics.

PMID- 23138303
TI  - Uniting ENCODE with genome-wide proteomics.

PMID- 23138305
TI  - Genome sequencing in clinical microbiology.

PMID- 23138306
TI  - Protein structure prediction from sequence variation.
AB  - Genomic sequences contain rich evolutionary information about functional
      constraints on macromolecules such as proteins. This information can be
      efficiently mined to detect evolutionary couplings between residues in proteins
      and address the long-standing challenge to compute protein three-dimensional
      structures from amino acid sequences. Substantial progress has recently been made
      on this problem owing to the explosive growth in available sequences and the
      application of global statistical methods. In addition to three-dimensional
      structure, the improved understanding of covariation may help identify functional
      residues involved in ligand binding, protein-complex formation and conformational
      changes. We expect computation of covariation patterns to complement experimental
      structural biology in elucidating the full spectrum of protein structures, their
      functional interactions and evolutionary dynamics.

PMID- 23138307
TI  - Genome interpretation and assembly-recent progress and next steps.

PMID- 23138308
TI  - The expanding scope of DNA sequencing.
AB  - In just seven years, next-generation technologies have reduced the cost and
      increased the speed of DNA sequencing by four orders of magnitude, and
      experiments requiring many millions of sequencing reads are now routine. In
      research, sequencing is being applied not only to assemble genomes and to
      investigate the genetic basis of human disease, but also to explore myriad
      phenomena in organismic and cellular biology. In the clinic, the utility of
      sequence data is being intensively evaluated in diverse contexts, including
      reproductive medicine, oncology and infectious disease. A recurrent theme in the
      development of new sequencing applications is the creative 'recombination' of
      existing experimental building blocks. However, there remain many potentially
      high-impact applications of next-generation DNA sequencing that are not yet fully
      realized.

PMID- 23138312
TI  - Third-quarter biotech job picture.

PMID- 23138309
TI  - Interpreting noncoding genetic variation in complex traits and human disease.
AB  - Association studies provide genome-wide information about the genetic basis of
      complex disease, but medical research has focused primarily on protein-coding
      variants, owing to the difficulty of interpreting noncoding mutations. This
      picture has changed with advances in the systematic annotation of functional
      noncoding elements. Evolutionary conservation, functional genomics, chromatin
      state, sequence motifs and molecular quantitative trait loci all provide
      complementary information about the function of noncoding sequences. These
      functional maps can help with prioritizing variants on risk haplotypes, filtering
      mutations encountered in the clinic and performing systems-level analyses to
      reveal processes underlying disease associations. Advances in predictive modeling
      can enable data-set integration to reveal pathways shared across loci and
      alleles, and richer regulatory models can guide the search for epistatic
      interactions. Lastly, new massively parallel reporter experiments can
      systematically validate regulatory predictions. Ultimately, advances in
      regulatory and systems genomics can help unleash the value of whole-genome
      sequencing for personalized genomic risk assessment, diagnosis and treatment.

PMID- 23138310
TI  - Mapping recently identified nucleotide variants in the genome and transcriptome.
AB  - Nucleotide variants, especially those related to epigenetic functions, provide
      critical regulatory information beyond simple genomic sequence, and they define
      cell status in higher organisms. 5-Methylcytosine, which is found in DNA, was
      until recently the only nucleotide variant studied in terms of epigenetics in
      eukaryotes. However, 5-methylcytosine has turned out to be just one component of
      a dynamic DNA epigenetic regulatory network that also includes 5
      hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine. Recently,
      reversible methylation of N6-methyladenosine in RNA has also been demonstrated.
      The discovery of these new nucleotide variants triggered an explosion of new
      information in the epigenetics field. This rapid research progress has benefited
      significantly from timely developments of new technologies that specifically
      recognize, enrich and sequence nucleotide modifications, as evidenced by the wide
      application of the bisulfite sequencing of 5-methylcytosine and very recent
      modifications of bisulfite sequencing to resolve 5-hydroxymethylcytosine from 5
      methylcytosine with base-resolution information.

PMID- 23138316
TI  - [Discovery of voltage-gated sodium-channel blockers for the treatment of
      neuropathic pain].

PMID- 23138315
TI  - [Novel therapeutic approach to neuropathic pain: "Hot" and "Cool" TRP-channel
      family].

PMID- 23138311
TI  - Pharmacogenomics in clinical practice and drug development.
AB  - Genome-wide association studies (GWAS) of responses to drugs, including
      clopidogrel, pegylated-interferon and carbamazepine, have led to the
      identification of specific patient subgroups that benefit from therapy. However,
      the identification and replication of common sequence variants that are
      associated with either efficacy or safety for most prescription medications at
      odds ratios (ORs) >3.0 (equivalent to >300% increased efficacy or safety) has yet
      to be translated to clinical practice. Although some of the studies have been
      completed, the results have not been incorporated into therapy, and a large
      number of commonly used medications have not been subject to proper
      pharmacogenomic analysis. Adoption of GWAS, exome or whole genome sequencing by
      drug development and treatment programs is the most striking near-term
      opportunity for improving the drug candidate pipeline and boosting the efficacy
      of medications already in use.

PMID- 23138317
TI  - [Immunoregulatory molecules reveal crosstalk between immune and pain responses].

PMID- 23138318
TI  - [New methodologies in drug discovery research for analgesic agents: automated
      measurement of spontaneous pain-associated animal behaviors for alignment of
      preclinical/clinical endpoints].

PMID- 23138319
TI  - [Recent topics concerning microglia-accumulating evidence for the physiological
      roles of microglia in the normal brain].

PMID- 23138320
TI  - [Toxicogenomics and biomarkers].

PMID- 23138321
TI  - Chromophore/fluorophore-assisted light inactivation method.

PMID- 23138322
TI  - [Benefit and risk management in product life cycle].

PMID- 23138323
TI  - [Pharmacological profiles and clinical roles of 5-azacitidine (Vidaza((r)) for
      injection 100 mg) for the treatment of myelodysplastic syndrome (MDS)].

PMID- 23138324
TI  - Unfavourable cardiovascular disease risk profiles in a cohort of Dutch and
      British haemophilia patients.
AB  - Cardiovascular disease (CVD) mortality is reported to be decreased in haemophilia
      patients, but reports on the prevalence of CVD risk factors are conflicting. A
      cross-sectional assessment of CVD risk profiles was performed in a large cohort
      of haemophilia patients. Baseline data on CVD risk factors of 709 Dutch and UK
      haemophilia patients aged >=30 years were analysed and compared with the general
      age-matched male population. CVD risk profiles were assessed using the QRISK(r)2
      2011 and SCORE algorithms. Although QRISK(r) 2 was only validated in the UK,
      comparison with SCORE indicated similar properties of  QRISK(r)2 in both Dutch
      and UK patients (correlation 0.86). Mean age was 49.8 years. Hypertension was
      more common in haemophilia patients than in the general population (49% vs. 40%),
      while the prevalences of obesity and hypercholesterolaemia were lower  (15 vs.
      20% and 44 vs. 68%, respectively), and those of diabetes and smoking were
      similar. The predicted 10-year QRISK(r)2 risk was significantly higher in
      haemophilia patients than in the general population (8.9 vs. 6.7%), indicating
      more unfavourable cardiovascular disease risk profiles. This increased risk
      became apparent after the age of 40 years. Our results indicate an increased
      prevalence of hypertension and overall more unfavourable CVD risk profiles in
      haemophilia patients compared with the general age-matched male population.

PMID- 23138325
TI  - [New and old challenges].

PMID- 23138326
TI  - [The potential of selective contracts in Germany--pro].

PMID- 23138327
TI  - [Selective contracts in Germany--contra].

PMID- 23138328
TI  - [Social skills training in severe mental illness--is it effective?].
AB  - OBJECTIVE: To report about existing evidence of effectiveness of social skills
      training for severely mentally ill adults. METHODS: Systematic electronic and
      manual literature search for systematic reviews and randomized clinical trials
      (RCTs). RESULTS: Social skills training is a widely used intervention for people
      with severe mental illness. We identified four reviews and seven RCTs
      demonstrating the efficacy and effectiveness of social skills training. Results
      suggest that patients would benefit from trainings by improving social skills and
      social functioning. There are ambiguous results regarding other outcomes.
      CONCLUSIONS: People with severe mental illness should be provided with social
      skills training, if necessary, combined with cognitive remediation. Those
      techniques are required which actively support the generalization of positive
      achievements into patients' natural environments.

PMID- 23138329
TI  - [Cost-effectiveness of needs-oriented discharge planning in high utilizers of
      mental health care].
AB  - OBJECTIVE: To establish the cost-effectiveness of needs-oriented discharge
      planning in high utilizers of mental health services. METHODS: As part of a
      multicenter RCT (n = 458), costs were measured via the German version of the
      "Client Sociodemographic and Service Receipt Inventory" (CSSRI-EU), and the EQ-5
      D was used to ascertain QALYs. Cost-effectiveness analysis included deriving
      incremental cost-effectiveness ratios (ICERs) and plotting them onto the cost
      effectiveness plane as well as examining cost-effectiveness acceptability taking
      into account willingness-to-pay. RESULTS: During an 18-month period after
      discharge from inpatient psychiatric treatment, neither total direct and indirect
      costs (44,278 ? vs. 43,302 ?) nor quality-adjusted life years (0.960 vs. 0.958
      QALYs) significantly differed by participant allocation to intervention or
      control groups. Also inspection of ICERs showed that the intervention had no
      economic advantage over standard care. CONCLUSIONS: The intervention is no cost
      effective alternative to standard care. Future studies aiming to improve
      organization of mental care should be considerate of institutional context.

PMID- 23138330
TI  - [Working with a family systems therapy approach as part of the routine treatment
      on acute psychiatric wards: sustained effects on team members' workload].
AB  - OBJECTIVE: Assessing long-term effects of a family systems therapy approach
      (systems therapy methods in acute psychiatry, SYMPA) on occupational stress and
      interdisciplinary cooperation of team members in three German psychiatric
      hospitals. METHODS: Pre-post-follow-up survey using the Maslach Burnout Inventory
      (MBI) and Team Climate Inventory (TCI) questionnaires complemented by semi
      structured in-depth interviews (N = 56). RESULTS: Three years after implementing
      a family systems therapy approach, experienced work load and staff burnout remain
      significantly lower than before. Interdisciplinary cooperation was intensified
      and nursing staff status increased. Following systemic case conceptualisations
      and interventions the therapeutic alliance moved towards a need-adapted treatment
      approach. CONCLUSIONS: Seven years after implementation, the family systems
      therapy approach still included significantly lower workload burden, an
      intensified interdisciplinary cooperation, and a need-adapted treatment
      orientation that strengthens the alliance between staff and client system.

PMID- 23138332
TI  - On the spur lifetime and its temperature dependence in the low linear energy
      transfer radiolysis of water.
AB  - In the spirit of the radiation chemical "spur model", the lifetime of a spur
      (tau(s)) is an important indicator of overlapping spurs and the establishment of
      homogeneity in the distribution of reactive species created by the action of low
      linear energy transfer (LET) radiation (such as fast electrons or gamma
      irradiation). In fact, tau(s) gives the time required for the changeover from
      nonhomogeneous spur kinetics to homogeneous kinetics in the bulk solution, thus
      defining the so-called primary (or "escape") radical and molecular yields of
      radiolysis, which are obviously basic to the quantitative understanding of any
      irradiated chemical system. In this work, tau(s) and its temperature dependence
      have been determined for the low-LET radiolysis of deaerated 0.4 M aqueous
      solutions of H(2)SO(4) and pure liquid water up to 350  degrees C using a simple
      model of energy deposition initially in spurs, followed by random diffusion of
      the species of the spur during track expansion until spur overlap is complete.
      Unlike our previous tau(s) calculations, based on irradiated Fricke dosimeter
      simulations, the current model is free from any effects due to the presence of
      oxygen or the use of scavengers. In acidic solutions, the spur lifetime values
      thus obtained are in very good agreement with our previous calculations (after
      making appropriate corrections, however, to account for the possibility of
      competition between oxygen and Fe(2+) ions for H atoms in the Fricke dosimeter,
      an effect which was not included in our original simulations). In this way, we
      confirm the validity of our previous approach. As expected, in the case of pure,
      oxygen-free water, our calculated times required to reach complete spur overlap
      are essentially the same (within uncertainty limits) as those found in acidic
      solutions. This explicitly reflects the fact that the diffusion coefficients for
      the hydrated electron and the H atom that are involved in the overall calculation
      of the lifetime of spurs in neutral or acidic media, respectively, are of similar
      magnitude over the 25-350  degrees C temperature range studied.

PMID- 23138331
TI  - [Phenomenological anthropological social psychiatry--paving the way for a
      theoretical reanimation].
AB  - This article tries to link the present lack of theoretical discussion within
      German Social Psychiatry with a loss of phenomenological and anthropological
      thought. The so-called Phenomenological Psychiatry used to play a very important
      role in German psychiatry during the 50 ies until the 70 ies and had strong
      influences on the first reformers of German psychiatry, such as Walter Ritter von
      Baeyer, Heinz Hafner, Caspar Kulenkampff, Karl Peter Kisker and Erich Wulff.
      Their reforms were not only founded by a social criticism put forth by theories
      such as marxism (Basaglia, Wulff) or structuralism (Foucault) but also by a
      concrete notion of what it is like to suffer from mental illness and what kind of
      needs are linked to such suffering. This very notion was given by the
      phenomenological approach. Finally the article tries to give reasons for today's
      reciprocal loss of connection of the phenomenological and the socio-psychiatric
      school.

PMID- 23138333
TI  - The effect of copper on different phototrophic microorganisms determined in vivo
      and at cellular level by confocal laser microscopy.
AB  - Microbial mats are coastal ecosystems that consist mainly of cyanobacteria,
      primary producers in these habitats that play an important role in stabilising
      delta sediments. However, these ecosystems are subject to various kinds of
      pollution, including metal contamination, placing their survival at risk. Among
      heavy metals, copper is an essential metal at low doses and toxic at high doses.
      This metal is present in different pesticides used in rice production, a thriving
      agro-industry in the Ebro Delta (Spain). For several years, our group has been
      studying the Ebro Delta microbial mats and has developed a method for determining
      the effect that metals cause on cyanobacteria populations. This method is based
      on confocal laser microscopy coupled to a spectrofluorometer, which rapidly
      provides simultaneous three-dimensional information on photosynthetic
      microorganisms and their fluorescence spectra profiles. The current study
      determines the copper effect on different photosynthetic microorganisms from
      culture collection (Chroococcus sp. PCC 9106 and Spirulina sp. PCC 6313) and
      isolated from the environment (Microcoleus-like and the microalga DE2009).
      Comparing all results obtained it can be observed that the minimum dose of Cu
      that is capable of significantly altering chlorophyll a (chl a) fluorescence
      intensity were 1 * 10(-7) M in Chroococcus sp. PCC 9106; 1 * 10(-7) M in
      Spirulina sp. PCC 6313; 3 * 10(-7) M in Microcoleus and 5 * 10(-6) M in the
      microalga DE2009. Moreover, the sensitivity of the technique used was 1 * 10(-7)
      M.

PMID- 23138334
TI  - Alleviation effects of magnesium on copper toxicity and accumulation in grapevine
      roots evaluated with biotic ligand models.
AB  - Copper toxicity and accumulation in plants are affected by physicochemical
      characteristics of soil solutions such as the concentrations of coexistent
      cations (e.g., Ca(2+), Mg(2+), K(+), Na(+), and H(+)). The biotic ligand model
      (BLM) approach has been proposed to predict metal phyto-toxicity and 
      accumulation by taking into account the effects of coexistent cations, given the
      assumption of the partition equilibrium of metal ions between soil solution and
      solid phase. The alleviation effects of Mg on Cu toxicity and accumulation in
      grapevine roots were the main concerns in this study and were investigated by
      using a hydroponic experiment of grapevine cuttings. The BLM approach, which
      incorporated competition of Mg(2+) with Cu(2+) to occupy the biotic ligands on
      root surfaces, was developed to predict Cu rhizotoxicity and accumulation by
      grapevine roots. In the results, the effective activity of Cu, {Cu (2+)},
      resulting in a 50 % reduction of root elongation (EA (50)), linearly increased
      with increments of Mg activity, {Mg (2+)}. In addition, the Cu concentration in
      root, Cu ( root ), was retarded by an increase of {Mg (2+)}. The linear model was
      significantly fitted to the relationship between {Cu (2+)}/Cu ( root ) and {Mg
      (2+)}. According to the concept of BLM, the present results revealed that the
      amelioration effects of Mg on Cu toxicity and accumulation in roots could arise
      from competition between Mg(2+) and Cu(2+) on the binding sites (i.e., the biotic
      ligands). Then, the developed Cu-BLMs incorporating the Mg(2+) competition
      effectiveness were validated provide accurate predictions of Cu toxicity and
      accumulation in grapevine roots. To our knowledge this is the first report of the
      successful development of BLMs for a woody plant. This BLM approach shows promise
      of being widely applicable for various terrestrial plants.

PMID- 23138335
TI  - A long-term comparison of the influence of organic and conventional crop
      management practices on the content of the glycoalkaloid alpha-tomatine in
      tomatoes.
AB  - BACKGROUND: alpha-Tomatine, synthesized by Lycopersicon and some Solanum species,
      is a steroidal glycoalkaloid which functions to protect against pathogens and
      insects. Although glycoalkaloids are generally considered toxic, alpha-tomatine
      appears to be well tolerated in humans. alpha-Tomatine has numerous potential
      health benefits including the ability to inhibit cancer cell growth in in vitro
      studies. alpha-Tomatine is influenced by numerous agronomic factors including
      fertilization and nitrogen availability. Herein, the levels of alpha-tomatine
      were compared in dried tomato samples (Lycopersicon esculentum L. cv. Halley
      3155) produced in organic and conventional cropping systems that had been
      archived over the period from 1994 to 2004 from the Long Term Research on
      Agricultural Systems project (LTRAS) at UC Davis. RESULTS: The alpha-tomatine
      levels of tomatoes in both cropping systems ranged from 4.29 to 111.85 ug g(-1)
      dry weight. Mean levels of alpha-tomatine were significantly higher in the
      organically grown tomatoes than conventional ones (P < 0.001). In the organic
      management system, alpha-tomatine content was also significantly (P < 0.001)
      different between cropping years, suggesting that other influencing factors such
      as environmental conditions also affect alpha-tomatine content in tomato.
      CONCLUSIONS: The organically produced tomatoes had higher average alpha-tomatine
      content than their conventional counterpart over the 10-year study. Significant
      annual variability in the alpha-tomatine content in tomatoes was also observed
      and suggests that environmental factors, external to nitrogen fertilization,
      influence alpha-tomatine content in tomatoes.

PMID- 23138336
TI  - Chemometrics-based process analytical technology (PAT) tools: applications and
      adaptation in pharmaceutical and biopharmaceutical industries.
AB  - Process analytical technology (PAT) is used to monitor and control critical
      process parameters in raw materials and in-process products to maintain the
      critical quality attributes and build quality into the product. Process
      analytical technology can be successfully implemented in pharmaceutical and
      biopharmaceutical industries not only to impart quality into the products but
      also to prevent out-of-specifications and improve the productivity. PAT
      implementation eliminates the drawbacks of traditional methods which involves
      excessive sampling and facilitates rapid testing through direct sampling without
      any destruction of sample. However, to successfully adapt PAT tools into
      pharmaceutical and biopharmaceutical environment, thorough understanding of the
      process is needed along with mathematical and statistical tools to analyze large
      multidimensional spectral data generated by PAT tools. Chemometrics is a chemical
      discipline which incorporates both statistical and mathematical methods to obtain
      and analyze relevant information from PAT spectral tools. Applications of
      commonly used PAT tools in combination with appropriate chemometric method along
      with their advantages and working principle are discussed. Finally, systematic
      application of PAT tools in biopharmaceutical environment to control critical
      process parameters for achieving product quality is diagrammatically represented.

PMID- 23138337
TI  - Perspectives in metabolic engineering: understanding cellular regulation towards
      the control of metabolic routes.
AB  - Metabolic engineering seeks to redirect metabolic pathways through the
      modification of specific biochemical reactions or the introduction of new ones
      with the use of recombinant technology. Many of the chemicals synthesized via
      introduction of product-specific enzymes or the reconstruction of entire
      metabolic pathways into engineered hosts that can sustain production and can
      synthesize high yields of the desired product as yields of natural product
      derived compounds are frequently low, and chemical processes can be both energy
      and material expensive; current endeavors have focused on using biologically
      derived processes as alternatives to chemical synthesis. Such economically
      favorable manufacturing processes pursue goals related to sustainable development
      and "green chemistry". Metabolic engineering is a multidisciplinary approach,
      involving chemical engineering, molecular biology, biochemistry, and analytical
      chemistry. Recent advances in molecular biology, genome-scale models, theoretical
      understanding, and kinetic modeling has increased interest in using metabolic
      engineering to redirect metabolic fluxes for industrial and therapeutic purposes.
      The use of metabolic engineering has increased the productivity of industrially
      pertinent small molecules, alcohol-based biofuels, and biodiesel. Here, we
      highlight developments in the practical and theoretical strategies and
      technologies available for the metabolic engineering of simple systems and
      address current limitations.

PMID- 23138339
TI  - Bromide ion binding by a dinuclear gold(I) N-heterocyclic carbene complex: a
      spectrofluorescence and X-ray absorption spectroscopic study.
AB  - Fluorescence and X-ray absorption spectroscopy were used to investigate the anion
      binding properties of a luminescent, dinuclear Au(I) N-heterocyclic carbene (NHC)
      complex ([1](2+)) with a short Au(I)...Au(I) contact. The addition of Br(-) ions
      to a DMSO solution of [1](PF(6))(2) caused a red-shift in the fluorescence
      emission band from 396 nm to 496 nm. Similarly, the addition of Br(-) ions to
      [1](PF(6))(2) caused a decrease in the energy of the Au L(3)-edge in the X-ray
      absorption spectrum, consistent with the formation of an association complex
      between the cation [1](2+) and Br(-) ions. Solution-based structural studies of
      the association complex were carried out using extended X-ray absorption fine
      structure (EXAFS) modelling of the Au(I)...Au(I) core of the cation. These
      studies indicate that the association complex results from Au(I)...Br(-)
      interactions, with the Br(-) ions occupying two partially occupied sites at ~2.9
      and 3.9 A from the Au(I) atoms.

PMID- 23138338
TI  - Long-term HIV infection and antiretroviral therapy are associated with bone
      microstructure alterations in premenopausal women.
AB  - We evaluated the influence of long-term HIV infection and its treatment on distal
      tibia and radius microstructure. Premenopausal eumenorrheic HIV-positive women
      displayed trabecular and cortical microstructure alterations, which could
      contribute to increased bone fragility in those patients. INTRODUCTION: Bone
      fragility is an emerging issue in HIV-infected patients. Dual-energy X-ray
      absorptiometry (DXA) quantified areal bone mineral density (BMD) predicts
      fracture risk, but a significant proportion of fracture risk results from
      microstructural alterations. METHODS: We studied the influence of long-term HIV
      infection on bone microstructure as evaluated by high-resolution peripheral
      quantitative computed tomography (HR-pQCT) in 22 HIV-positive (+ve) premenopausal
      eumenorrheic women and 44 age- and body mass index (BMI)-matched HIV-negative (
      ve) controls. All subjects completed questionnaires regarding calcium/protein
      intakes and physical activity, and underwent DXA and HR-pQCT examinations for BMD
      and peripheral skeleton microstructure, respectively. A risk factor analysis of
      tibia trabecular density using linear mixed models was conducted. RESULTS: In
      HIV+ve women on successful antiretroviral therapy (undetectable HIV-RNA, median
      CD4 cell count, 626), infection duration was 16.5 +/- 3.5 (mean +/- SD) years;
      median BMI was 22 (IQR, 21-26) kg/m2. More HIV+ve women were smokers (82 versus
      50 %, p = 0.013). Compared to controls, HIV+ve women had lower lumbar spine
      (spine T-score -0.70 vs -0.03, p = 0.014), but similar proximal femur BMD. At
      distal tibia, HIV+ve women had a 14.1 % lower trabecular density and a 13.2 %
      reduction in trabecular number compared to HIV-ve women (p = 0.013 and 0.029,
      respectively). HR-pQCT differences in distal radius were significant for cortical
      density (-3.0 %; p = 0.029). CONCLUSIONS: Compared with HIV-ve subjects,
      premenopausal HIV+ve treated women had trabecular and cortical bone alterations.
      Adjusted analysis revealed that HIV status was the only determinant of between
      group tibia trabecular density differences. The latter could contribute to
      increased bone fragility in HIV+ve patients.

PMID- 23138340
TI  - The effect of copper(II), iron(II) sulphate, and vitamin C combinations on the
      weak antimicrobial activity of (+)-catechin against Staphylococcus aureus and
      other microbes.
AB  - Few attempts have been made to improve the activity of plant compounds with low
      antimicrobial efficacy. (+)-Catechin, a weak antimicrobial tea flavanol, was
      combined with putative adjuncts and tested against different species of bacteria.
      Copper(II) sulphate enhanced (+)-catechin activity against Pseudomonas aeruginosa
      but not Staphylococcus aureus, Proteus mirabilis or Escherichia coli. Attempts to
      raise the activity of (+)-catechin against two unresponsive species, S. aureus
      and E. coli, with iron(II) sulphate, iron(III) chloride, and vitamin C, showed
      that iron(II) enhanced (+)-catechin against S. aureus, but not E. coli; neither
      iron(III) nor combined iron(II) and copper(II), enhanced (+)-catechin activity
      against either species. Vitamin C enhanced copper(II) containing combinations
      against both species in the absence of iron(II). Catalase or EDTA added to active
      samples removed viability effects suggesting that active mixtures had produced
      H(2)O(2)via the action of added metal(II) ions. H(2)O(2) generation by (+)
      catechin plus copper(II) mixtures and copper(II) alone could account for the
      principal effect of bacterial growth inhibition following 30 minute exposures as
      well as the antimicrobial effect of (+)-catechin-iron(II) against S. aureus.
      These novel findings about a weak antimicrobial flavanol contrast with previous
      knowledge of more active flavanols with transition metal combinations. Weak
      antimicrobial compounds like (+)-catechin within enhancement mixtures may
      therefore be used as efficacious agents. (+)-Catechin may provide a means of
      lowering copper(II) or iron(II) contents in certain crop protection and other
      products.

PMID- 23138341
TI  - Measure for the assessment of confidence with manual wheelchair use (WheelCon-M)
      version 2.1: reliability and validity.
AB  - OBJECTIVE: To evaluate the measurement properties of the Wheelchair Use
      Confidence Scale for manual wheelchair users version 2.1 (WheelCon-M 2.1).
      DESIGN: Cohort study. PARTICIPANTS: Volunteer sample of 83 community-dwelling,
      experienced manual wheelchair users. METHODS: Participants completed the WheelCon
      M 2.1 twice to assess retest reliability. Validity was assessed by evaluating
      hypothesized relationships between the WheelCon-M 2.1 and relevant variables.
      Responsiveness was assessed using the standard error of measurement (SEM) and
      smallest real difference (SRD). RESULTS: The median (interquartile range)
      WheelCon-M 2.1 score was 84.6 (71.3-92.0) of a possible 0-100. The one-week
      retest intraclass correlation coefficient was 0.84 with 95% bias-corrected and
      accelerated confidence intervals of 0.77-0.90. Cronbach's alpha was 0.92.
      Correlations ranging from rs = -0.19 (p = 0.780) to rs = 0.58 (p < 0.001) were
      found between the WheelCon-M 2.1 and other relevant outcome measures with all
      correlations being statistically significant except for age (p = 0.780) and
      social support (p = 0.057). A statistically significant difference was not found
      between the sexes (p = 0.140). The SEM and SRM were 5.9 and 16.4, respectively.
      CONCLUSIONS: WheelCon-M 2.1 has high internal consistency, strong retest
      reliability, and support for concurrent validity, construct validity and
      responsiveness. This new test holds promise as a clinical and research tool.

PMID- 23138342
TI  - The scope of prenatal diagnosis for women at increased risk for aneuploidies:
      views and preferences of professionals and potential users.
AB  - The increasing number of prenatal diagnostic tests in prenatal screening
      strategies, raises the question what tests to offer and why. This qualitative
      study investigated the views and preferences of professionals and potential users
      regarding four diagnostic test options for women at increased risk for common
      aneuploidies. Seven focus group sessions were conducted in The Netherlands
      between October 2009 and June 2010, with various categories of participants (n =
      55): professionals engaged in prenatal testing and potential users of this
      testing (meaning pregnant women and parents of young children). Participants were
      invited to mention all pros and cons and their preferences regarding four
      hypothetical diagnostic test options, presented on vignettes: a standard offer of
      rapid aneuploidy detection, karyotyping or array comparative genomic
      hybridization, representing a narrow, traditional and broad test, respectively,
      and the option of individualised choice. Then, a semi-structured group interview
      was conducted. The data were analysed by the constant comparative method.
      Participants identified similar test-specific pros and cons but showed different
      preferences. Users' opinion on what test to offer as a general policy differed
      from what they would choose themselves. All participants agreed that in theory,
      users should be enabled to make an informed choice about what test to apply, but
      they disagreed about the feasibility of this ideal. Standard narrow testing was
      favoured for its limiting effects on emotional and organisational burdens;
      individualised choice was preferred for assuring women's decisive influence. The
      varying opinions reflect different views on what autonomy in the prenatal
      screening context means, suggest that a single standard test offer is inadequate
      and that differentiation will be needed.

PMID- 23138343
TI  - Template-free synthesis of cube-like Ag/AgCl nanostructures via a direct
      precipitation protocol: highly efficient sunlight-driven plasmonic
      photocatalysts.
AB  - In this paper, we report that cube-like Ag/AgCl nanostructures could be facilely
      fabricated in a one-pot manner through a direct-precipitation protocol under
      ambient conditions, wherein no additional issues such as external energy (e.g.,
      high temperature or high pressure), surfactants, or reducing agents are required.
      In terms of using sodium chloride (NaCl) as chlorine source and silver acetate
      (CH3COOAg) as silver source, it is disclosed that simply by adding an aqueous
      solution of NaCl into an aqueous solution of CH3COOAg, Ag/AgCl nanostructures
      with a cube-like geometry, could be successfully formulated. We show that thus
      formulated cube-like Ag/AgCl nanospecies could be used as high-performance yet
      durable visible-light-driven or sunlight-driven plasmonic photocatalysts for the
      photodegradation of methyl orange (MO) and 4-chlorophenol (4-CP) pollutants.
      Compared with the commercially available P25-TiO2, and the Ag/AgCl nanospheres
      previously fabricated via a surfactant-assisted method, our current cube-like
      Ag/AgCl nanostructures could exhibit much higher photocatalytic performance. Our
      template free protocol might open up new and varied opportunities for an easy
      synthesis of cube-like Ag/AgCl-based high-performance sunlight-driven plasmonic
      photocatalysts for organic pollutant elimination.

PMID- 23138345
TI  - Combined depth imaging using optical coherence tomography as a novel imaging
      technique to visualize vitreoretinal choroidal structures.

PMID- 23138346
TI  - In situ monitoring of flash-light sintering of copper nanoparticle ink for
      printed electronics.
AB  - In this work, a flash-light sintering process for Cu nanoinks was studied. In
      order to precisely monitor the milliseconds flash-light sintering process, a real
      time Wheatstone bridge electrical circuit and a high-rate data acquisition system
      were used. The effects of several flash-light irradiation conditions (irradiation
      energy, pulse number, on-time, and off-time) and the effects of the amount of
      poly(N-vinylpyrrolidone) in the Cu nanoink on the flash-light sintering process
      were investigated. The microstructures of the sintered Cu films were analyzed by
      scanning electron microscopy. To investigate the oxidation or reduction of the
      oxide-covered copper nanoparticles, a crystal phase analysis using x-ray
      diffraction was performed. In addition, the sheet resistance of Cu film was
      measured using a four-point probe method. From this study, it was found that the
      flash-light sintered Cu nanoink films have a conductivity of 72 Omegam/sq without
      any damage to the polyimide substrate. Similar nanoinks are expected to be widely
      used in printed and flexible electronics products in the near future.

PMID- 23138344
TI  - Stem cell systems and regeneration in planaria.
AB  - Planarians are members of the Platyhelminthes (flatworms). These animals have
      evolved a remarkable stem cell system. A single pluripotent adult stem cell type
      ("neoblast") gives rise to the entire range of cell types and organs in the
      planarian body plan, including a brain, digestive-, excretory-, sensory- and
      reproductive systems. Neoblasts are abundantly present throughout the mesenchyme
      and divide continuously. The resulting stream of progenitors and turnover of
      differentiated cells drive the rapid self-renewal of the entire animal within a
      matter of weeks. Planarians grow and literally de-grow ("shrink") by the food
      supply-dependent adjustment of organismal turnover rates, scaling body plan
      proportions over as much as a 50-fold size range. Their dynamic body architecture
      further allows astonishing regenerative abilities, including the regeneration of
      complete and perfectly proportioned animals even from tiny tissue remnants.
      Planarians as an experimental system, therefore, provide unique opportunities for
      addressing a spectrum of current problems in stem cell research, including the
      evolutionary conservation of pluripotency, the dynamic organization of
      differentiation lineages and the mechanisms underlying organismal stem cell
      homeostasis. The first part of this review focuses on the molecular biology of
      neoblasts as pluripotent stem cells. The second part examines the fascinating
      mechanistic and conceptual challenges posed by a stem cell system that epitomizes
      a universal design principle of biological systems: the dynamic steady state.

PMID- 23138347
TI  - Mumps Hoshino and Torii vaccine strains were distinguished from circulating wild
      strains.
AB  - Aseptic meningitis and acute parotitis have been observed after mumps
      vaccination. Mumps outbreaks have been reported in Japan because of low vaccine
      coverage, and molecular differentiation is required to determine whether these
      cases are vaccine associated. RT-nested PCR was performed in the small
      hydrophobic gene region, and viruses were differentiated by restriction fragment
      length polymorphism assay. A total of 584 nucleotides were amplified. The PCR
      product of the Hoshino strain was cut into two fragments (313 and 271
      nucleotides) by MfeI; that of the Torii strain was digested with EcoT22I,
      resulting in 332- and 252-nucleotide fragments. Both strains were genotype B and
      had an XbaI site, resulting in two fragments: 299 and 285 nucleotides. Current
      circulating wild types were cut only by XbaI or MfeI. However, the MfeI site of
      the wild types was different from that of the Hoshino strain, resulting in 451-
      and 133-nucleotide fragments. Using three restriction enzymes, two mumps vaccine
      strains were distinguished from wild types, and this separation was applied to
      the identification of vaccine-related adverse events.

PMID- 23138348
TI  - Quality assurance for polychromatic flow cytometry using a suite of calibration
      beads.
AB  - The quality assurance program presented here provides a means to maximize and
      maintain the performance of individual flow cytometers in a facility. To optimize
      performance, we recommend performing all three steps (optimization, calibration
      and standardization) in this program when a new flow cytometer is installed or
      whenever the flow cytometer's optical path is altered (e.g., lasers, filters or
      detectors are replaced). The complete process requires 3-4 h. On a more frequent
      basis, only a subset of these procedures need to be performed as a part of daily
      maintenance routines. The data generated can be tracked to monitor the instrument
      and determine whether service is needed. In addition, the data can provide a
      metric for whether repairs and upgrades have improved or harmed performance, and
      for future instrument-to-instrument comparisons. In sum, the procedures presented
      here represent an updated framework for optimizing, calibrating and standardizing
      a flow cytometer for daily use.

PMID- 23138349
TI  - Generation of human induced pluripotent stem cells from urine samples.
AB  - Human induced pluripotent stem cells (iPSCs) have been generated with varied
      efficiencies from multiple tissues. Yet, acquiring donor cells is, in most
      instances, an invasive procedure that requires laborious isolation. Here we
      present a detailed protocol for generating human iPSCs from exfoliated renal
      epithelial cells present in urine. This method is advantageous in many
      circumstances, as the isolation of urinary cells is simple (30 ml of urine are
      sufficient), cost-effective and universal (can be applied to any age, gender and
      race). Moreover, the entire procedure is reasonably quick--around 2 weeks for the
      urinary cell culture and 3-4 weeks for the reprogramming--and the yield of iPSC
      colonies is generally high--up to 4% using retroviral delivery of exogenous
      factors. Urinary iPSCs (UiPSCs) also show excellent differentiation potential,
      and thus represent a good choice for producing pluripotent cells from normal
      individuals or patients with genetic diseases, including those affecting the
      kidney.

PMID- 23138350
TI  - Live imaging of cellular dynamics during Caenorhabditis elegans postembryonic
      development.
AB  - Postembryonic development is an important process of organismal maturation after
      embryonic growth. Despite key progress in recent years in understanding embryonic
      development via fluorescence time-lapse microscopy, comparatively less live-cell
      imaging of postembryonic development has been done. Here we describe a protocol
      to image larval development in the nematode Caenorhabditis elegans. Our protocol
      describes the construction of fluorescent transgenic C. elegans, immobilization
      of worm larvae and time-lapse microscopy analysis. To improve the throughput of
      imaging, we developed a C. elegans triple-fluorescence imaging approach with a
      worm-optimized blue fluorescent protein (TagBFP), green fluorescent protein (GFP)
      and mCherry. This protocol has been previously applied to time-lapse imaging
      analysis of Q neuroblast asymmetric division, migration and apoptosis, and we
      show here that it can also be used to image neuritogenesis in the L1 larvae.
      Other applications are also possible. The protocol can be completed within 3 h
      and may provide insights into understanding postembryonic development.

PMID- 23138351
TI  - A genome-wide sib-pair linkage analysis of ossification of the posterior
      longitudinal ligament of the spine.
AB  - Ossification of the posterior longitudinal ligament of the spine (OPLL) is a
      common musculoskeletal disease among people after middle age. The OPLL presents
      with serious neurological abnormalities due to compression of the spinal cord and
      nerve roots. The OPLL is caused by genetic and environment factors; however, its
      etiology and pathogenesis still remain to be elucidated. To determine the
      susceptibility loci for OPLL, we performed a genome-wide linkage study using 214
      affected sib-pairs of Japanese. In stratification analyses for definite cervical
      OPLL, we found loci with suggestive linkage on 1p21, 2p22-2p24, 7q22, 16q24 and
      20p12. Fine mapping using additional markers detected the highest non-parametric
      linkage score (3.43, P = 0.00027) at D20S894 on chromosome 20p12 in a subgroup
      that had no complication of diabetes mellitus. Our result would shed a new light
      on genetic aspects of OPLL.

PMID- 23138352
TI  - The effects of risedronate administered in combination with a proton pump
      inhibitor for the treatment of osteoporosis.
AB  - This study was performed to investigate the effects of the co-administration of
      proton pump inhibitor (PPI) on the efficacy of bisphosphonate (BP) treatment for
      osteoporosis. A total of 180 women with low bone mineral density were randomly
      divided into four groups, one in which sodium risedronate was administered with
      sodium rabeprazole and one in which only risedronate was administered (BP + PPI
      and BP groups, respectively). The biomarkers were measured at the baseline and
      every 3 months, inlcuding: N-terminal telopeptide of type I collagen corrected
      for creatinine, bone-specific alkaline phosphatase (BAP), parathyroid hormone,
      bone mineral density (BMD) of the lumbar spine and physical parameters evaluated
      according to the SF-36v2TM Health Survey. Statistical comparisons of these
      parameters were performed after 9 months. Data were available for a total of 137
      patients (62 in the BP group and 75 in the BP + PPI group). The Delta % value of
      increase in BMD and improvement of physical functioning in the BP + PPI group
      were significantly larger, and its decrease in BAP in the BP + PPI group was
      significantly smaller than that in the BP group. It is expected that risedronate
      administration in combination with a PPI may be more effective not only for
      treating osteoporosis but also improving physical fitness than treatment with
      risedronate alone.

PMID- 23138353
TI  - Comment on "Lymphocytic hypophysitis with proACTH".

PMID- 23138354
TI  - Effects of thirty-times chewing per bite on secretion of glucagon-like peptide-1
      in healthy volunteers and type 2 diabetic patients.
AB  - Glucagon-like peptide 1 (GLP-1) is secreted from the small intestine to the blood
      in response to glucose intake during a meal; however, it is not known whether
      mastication affects GLP-1 secretion. Here, we examined the relationship between
      mastication and GLP-1 secretion, along with postprandial blood glucose and
      insulin concentrations. We compared the levels of blood glucose, serum insulin,
      and plasma active GLP-1 concentrations after young healthy volunteers ate a test
      meal either by usual eating (control) or in one of three specified ways: 1.
      unilateral chewing, 2. quick eating, 3. 30-times chewing per bite. Ten volunteers
      participated in each of the three groups. Plasma active GLP-1 concentrations did
      not change by unilateral chewing or quick eating, but did increase by the third
      method, without affecting the concentrations of blood glucose or serum insulin.
      Next, we tested whether 30-times chewing per bite increased plasma active GLP-1
      concentrations in 15 patients with type 2 diabetes mellitus, but there was no
      difference in results between usual eating and 30-times chewing per bite. This is
      a pilot trial with a small number of subjects, but is the first study to
      investigate the relationships between various styles of mastication and the GLP-1
      secretion in young healthy volunteers and type 2 diabetic patients.

PMID- 23138356
TI  - A redox active proton transfer and hydrogen-bonding system of tetrathiafulvalene
      dicarboxylic acid and pyridine bases.
AB  - Hydrogen bonds are important in supramolecular chemistry and responsible for
      proton transfer processes. This manuscript reports new hydrogen-bonding systems
      of redox-active acid-base assemblies consisting of dimethylthio
      tetrathiafulvalene dicarboxylic acid (H(2)L) coupled with pyridine (py), 2,2'
      bipyridine (2,2'-bpy), and 4,4'-bipyridine (4,4'-bpy). The (1)H NMR chemical
      shifts of the pyridines and the redox potential shifts of the tetrathiafulvalene
      moiety indicate that proton-transfer and strong hydrogen-bonding interactions
      exist between the acid and the bases in aprotic solvents. The results of cyclic
      voltammetry show a two-step square reaction with a redox and proton transfer
      coupled mechanism. The nature of the hydrogen bonds was characterized by X-ray
      single crystal analysis. In contrast to the mono-carboxyl-py system, in this
      ortho-substituted dicarboxyl-py system one proton of the H(2)L transfers
      completely from the carboxyl to the py group. The conjugated intramolecular and
      intermolecular hydrogen bonds are responsible for the proton transfer.

PMID- 23138355
TI  - Comparison of two methods for selection of out of hospital treatment in patients
      with acute pulmonary embolism.
AB  - The aim of this study is to compare the performance of two clinical decision
      rules to select patients with acute pulmonary embolism (PE) for outpatient
      treatment: the Hestia criteria and the simplified Pulmonary Embolism Severity
      Index (sPESI). From 2008 to 2010, 468 patients with PE were triaged with the
      Hestia criteria for outpatient treatment: 247 PE patients were treated at home
      and 221 were treated as inpatients. The outcome of interest was all-cause 30-day
      mortality. In a post-hoc fashion, the sPESI items were scored and patients were
      classified according to the sPESI in low and high risk groups. Of the 247
      patients treated at home, 189 (77%) patients were classified as low risk
      according to the sPESI and 58 patients (23%) as high risk. In total, 11 patients
      died during the first month; two patients treated at home and nine patients
      treated in-hospital. None of the patients treated at home died of fatal PE. Both
      the Hestia criteria and sPESI selected >50% of patients as low risk, with good
      sensitivity and negative predictive values for 30-day mortality: 82% and 99% for
      the Hestia criteria and 91% and 100% for the sPESI, respectively. The Hestia
      criteria and the sPESI classified different patients eligible for outpatient
      treatment, with similar low risks for 30-day mortality. This study suggests that
      the Hestia criteria may identify a proportion of high risk sPESI patiennts who
      can be safely treated at home, this however requires further validation.

PMID- 23138357
TI  - An adult case of primary rhabdomyosarcoma of the trachea with resection of seven
      cartilage rings and primary reconstruction.
AB  - A 74-year-old female consulted a local clinic with bloody sputum and dyspnea.
      Bronchoscopy revealed a tumor with ~80% stenosis in the trachea. She was referred
      to our hospital. Biopsy findings suggested primary rhabdomyosarcoma of the
      trachea. Cervical computed tomography (CT) revealed a tumor involving the 3rd to
      9th tracheal cartilages. Tubular resection of the 3rd to 9th tracheal cartilages
      and tracheal reconstruction were performed. Finally, a pathological diagnosis of
      rhabdomyosarcoma was made. Primary rhabdomyosarcoma of the trachea is extremely
      rare.

PMID- 23138358
TI  - Cerebral protection during controlled hypoperfusion in a piglet model: comparison
      of moderate (25 degrees C) versus deep (18 degrees C) hypothermia at various flow
      rates using intraoperative measurements and ex vivo investigation.
AB  - BACKGROUND: During surgical correction of complex cardiac anomalies, some degree
      of hypoperfusion may be required. The aim of this study was to evaluate the
      effectiveness and safety of controlled cerebral hypoperfusion at moderate (25
      degrees C) versus deep (18 degrees C) hypothermia. METHODS: In this study, 56
      female piglets (9.4 +/- 0.8 kg, 3-4 weeks old) received cardiopulmonary bypass
      (CPB) at 25, 50, or 100% of the standard flow rate for 60 minutes of cardioplegic
      cardiac arrest. Body temperature was kept at 18, 25, and 37 degrees C. Routine
      hemodynamic and functional parameters were measured online until 4 hours of
      reperfusion. Immunohistology was used to quantify heat shock protein 70 (HSP70)
      and nitrotyrosine (NO-Tyr) levels in the hippocampus; high-performance liquid
      chromatography was used to quantify jugular venous blood malondialdehyde (MDA)
      levels. RESULTS: Reduced CPB flow led to significant reduction of mean arterial
      pressure by 79%, reduction of jugular venous oxygen saturation (SvO2) by 47%,
      reduction of carotid blood flow by 92%, and increase of serum lactate by 350%.
      All these changes were significantly enhanced in the 37 degrees C versus the 25
      and the 18 degrees C groups. Regional oxygen saturation (rSO2) was significantly
      reduced in the 37 degrees C low flow groups. HSP70, NO-Tyr, and MDA were
      increased in the 25 and 50% flow groups (p < 0.05). There was a significant
      correlation between rSO2 and SvO2 (r = 0.61) and between SvO2 and HSP70 (r = -
      0.72). CONCLUSIONS: Reduction in global blood flow during CPB leads to comparable
      biochemical changes in the hippocampus at 25 and 18 degrees C. Regional
      oxygenation saturation, SvO2, and HSP70 are important parameters to evaluate the
      efficacy of further anti-ischemic therapies during surgical corrections.

PMID- 23138359
TI  - Mesostructured fatty acid-tethered silicas: sustaining the order by co-templating
      with bulky precursors.
AB  - The co-condensation of functional alkoxysilanes with tetraethoxysilane in the
      presence of a structure directing agent under sol-gel process chemistry is a
      common way to access functional organosilica with an ordered mesostructure. In
      this report, bulky silylated fatty acid methyl esters were used both as co
      templating bio-molecules and functionalizing agents in the process of supra
      molecular silica mineralization. The highest structural regularity in terms of
      pore size distribution and channel size homogeneity was observed for carboxy
      tethered silica possessing SBA-15-type architecture due to an enhanced fatty acid
      precursor-surfactant interaction. The carboxylic surface embedded within the
      hydrophobic environment of the fatty compounds confers to these materials
      interesting reactive-surface properties with promising applications as drug
      delivery systems and bio-catalytic nanoreactors.

PMID- 23138360
TI  - Battles over the sexes.

PMID- 23138361
TI  - Culture and cutting.

PMID- 23138362
TI  - When is a failure of imagination dangerous?

PMID- 23138363
TI  - The doctor-patient relationship (when you're neither).

PMID- 23138364
TI  - Discrimination and the religious workplace.

PMID- 23138365
TI  - Toward acceptance of uterus transplants.

PMID- 23138366
TI  - Physician, patient, parent: where exactly is the line?

PMID- 23138367
TI  - Seven things to know about female genital surgeries in Africa.

PMID- 23138368
TI  - Aesthetic enhancement? Or human rights violation?

PMID- 23138369
TI  - The ethics of evidence.

PMID- 23138370
TI  - Using facts to moderate the message.

PMID- 23138371
TI  - Normalizing atypical genitalia: how a heated debate went astray.

PMID- 23138376
TI  - Clinicians' power and leadership.

PMID- 23138377
TI  - Latitudes and longitudes.

PMID- 23138378
TI  - Contrasting cellular uptake pathways for chlorido and iodido iminopyridine
      ruthenium arene anticancer complexes.
AB  - The pathways involved in cellular uptake and accumulation of iminopyridine
      complexes of general formula [Ru(eta(6)-p-cymene)(N,N-dimethyl-N'-[(E)-pyridine-2
      ylmethylidene]benzene-1,4-diamine)X]PF(6) bearing two different halido ligands X
      = Cl or I, have been explored. The ratio of passive/active cellular accumulation
      of Ru in A2780 human ovarian cancer cells is compared and contrasted with
      cisplatin. Also, saturation of cellular uptake, time-dependence of cellular
      influx/efflux equilibria, together with endocytotic pathways such as caveolae and
      facilitated diffusion are investigated and discussed. Temperature dependence
      studies of Ru accumulation in the A2780 cells show that in contrast to cisplatin
      (CDDP) and chlorido complex , which are taken up largely through active
      transport, the iodido complex enters cells via passive transport. The cellular
      efflux of Ru is slow (ca. 25% retained after 72 h) and is partially inhibited by
      verapamil, implicating the P-gp protein in the efflux mechanism. Ouabain
      inhibition experiments suggest that the cellular uptake of these ruthenium
      complexes relies at least in part on facilitated diffusion, and in particular is
      dependent on the membrane potential. In addition the finding that depletion of
      cellular ATP with antimycin A had little effect on cellular Ru accumulation from
      iodido complex is consistent with passive diffusion. In contrast, ATP depletion
      caused a major increase in cellular accumulation of ruthenium from chlorido
      complex .

PMID- 23138379
TI  - Association of pre-miRNA-146a rs2910164 and pre-miRNA-499 rs3746444 polymorphisms
      and susceptibility to rheumatoid arthritis.
AB  - Single nucleotide polymorphisms in pre-microRNA (miRNA) may alter miRNA
      expression levels or processing and contribute to susceptibility in a wide range
      of diseases. The present study aimed to evaluate the possible association between
      rs2910164 and rs3746444 of the pre-miRNA (hsa-mir-146a and hsa-mir-499)
      polymorphisms and susceptibility to rheumatoid arthritis (RA) in an Iranian
      population. This case-control study was performed on 104 patients with RA and 110
      healthy individuals. Tetra amplification refractory mutation system-polymerase
      chain reaction was used to genotype the hsa-mir-499 rs3746444 and hsa-mir-146a
      rs2910164 polymorphisms. The hsa-mir-499 rs3746444 polymorphism was a risk factor
      for predisposition to RA in codominant [TT vs. TC: odds ratio (OR), 2.11; 95%
      confidence interval (CI), 1.08-4.11; p=0.029; TT vs. CC: OR, 3.88; 95% CI, 1.68
      8.98; p=0.002], dominant (TT vs. TC-CC: OR, 2.64; 95% CI, 1.48-4.72; p=0.001) and
      recessive (TC-CC vs. CC: OR, 3.05; 95% CI, 1.36-6.83; p=0.007) tested inheritance
      models. In addition, the rs3746444 C allele was a risk factor for RA (OR, 2.49;
      95% CI, 1.63-3.81; p<0.0001). No significant difference was found between the
      groups concerning the rs2910164 polymorphism (chi2=0.348, p=0.841). Our findings
      demonstrated that the hsa-mir-499 rs3746444, but not mir-146a rs2910164,
      polymorphism is associated with an increased RA risk in a sample of the Iranian
      population. Larger studies with different ethnicities are required to validate
      our findings.

PMID- 23138380
TI  - Intergenerational educational mobility on general mental health and depressive
      symptoms in young women.
AB  - PURPOSE: To investigate how intergenerational educational mobility between women
      and their parents influences mental health/depressive symptoms in women. METHOD:
      We studied 5,619 women aged 31-36 years in 2009 from the Australian Longitudinal
      Study on Women's Health. The short-form-36 Mental Component Summary Scores [MCS]
      measured mental health and the Centre for Epidemiologic Studies Depression Scale
      [CES-D] measured depressive symptoms. Multiple regression analyses, with
      adjustment for confounders, were used. RESULTS: Greater downward mobility from
      mothers (mother high to self low) [MCS regression estimate [beta] -3.35; 95%
      confidence interval [CI] -5.6,-1.1; CES-D beta 1.94; 95% CI, 0.7,3.2], and
      greater (father high to self low MCS beta,-2.53; 95% CI -4.8,-0.3] and moderate
      (father high to self intermediate MCS beta -1.71; 95% CI -3.3,-0.1] downward
      mobility from fathers were associated with poorer mental health in women. Another
      strongly consistent influence on poor mental health was answering 'don't know/not
      applicable' about parental education [mother-self MCS beta -1.34; 95% CI, -2.3,
      0.4; mother-self CES-D beta 0.52; 95% CI 0.01,1.0; father-self MCS beta -1.19;
      95% CI -2.1,-0.3]. CONCLUSIONS: There are subtle differences for same and
      opposite-sex parent-daughter relationships on the impact of downwards
      intergenerational educational mobility on mental health in young women. These
      results suggest the effect of own educational attainment on mental health depends
      on the degree of disparity between self and parent. Future studies should
      consider 'don't know' as a separate category rather than treating it as a
      'missing' response.

PMID- 23138381
TI  - New results on formaldehyde: the 2nd International Formaldehyde Science
      Conference (Madrid, 19-20 April 2012).
AB  - The toxicology and epidemiology of formaldehyde were discussed on the 2nd
      International Formaldehyde Science Conference in Madrid, 19-20 April 2012. It was
      noted that a substantial amount of new scientific data has appeared within the
      last years since the 1st conference in 2007. Progress has been made in
      characterisation of genotoxicity, toxicokinetics, formation of exogenous and
      endogenous DNA adducts, controlled human studies and epidemiology. Thus, new
      research results are now at hand to be incorporated into existing evaluations on
      formaldehyde by official bodies.

PMID- 23138382
TI  - Added value of subtraction imaging in detecting arterial enhancement in small (<3
      cm) hepatic nodules on dynamic contrast-enhanced MRI in patients at high risk of
      hepatocellular carcinoma.
AB  - OBJECTIVES: To determine the importance of arterial enhancement in diagnosing
      small (<3 cm) hepatocellular carcinomas (HCCs) and to evaluate the added value of
      dynamic subtraction magnetic resonance imaging (MRI) in detecting arterial
      enhancement in small (<3 cm) hepatic nodules in high-risk patients. METHODS:
      Eighty-six patients with 135 pathologically confirmed small (<3 cm) hepatic
      nodules (104 HCCs, 31 benign nodules) underwent MRI before curative surgery.
      Arterial enhancement was determined by three methods: (1) visual assessment of
      the arterial phase alone, (2) visual comparison of the arterial phase with the
      unenhanced phase and (3) additional review of subtraction images. The diagnostic
      performance of each method was calculated and compared using generalised
      estimating equations analysis. RESULTS: Arterial enhancement demonstrated high
      positive predictive value (PPV) (96.5-98.9 %) and specificity (90.3-96.8 %), but
      low negative predictive value (NPV) (54.6-62.5 %) and intermediate sensitivity
      (76-79.8 %) for diagnosing small HCCs. Diagnostic performance was highest for
      subtraction imaging. There were significant differences among the three methods
      in sensitivity (P = 0.04), accuracy (P = 0.044), PPV (P < 0.001) and NPV (P =
      0.024), but not in specificity (P = 0.167). CONCLUSION: The accurate detection of
      arterial enhancement in small hepatic nodules is important for diagnosing HCC and
      may be enhanced by subtraction imaging.

PMID- 23138383
TI  - Unit costs in population-based colorectal cancer screening using CT colonography
      performed in university hospitals in The Netherlands.
AB  - OBJECTIVES: Computed tomography (CT) colonography cost assumptions so far ranged
      from <euro>346 to <euro>594 per procedure, based on clinical CT reimbursement
      rates. The aim of our study was to estimate the costs in a screening situation.
      METHODS: Data were collected within an invitational population-based CRC
      screening trial (n = 2,920, age 50-75 years) with a dedicated CT-screening
      setting. Unit costs were calculated per action, per invitee and per participant
      (depending on adherence) and per individual with detected advanced neoplasia.
      Sensitivity analyses were performed, and alternative scenarios were considered.
      RESULTS: Of the invitees, 47.2 % were reminded, 38.8 % scheduled for an intake,
      37.2 % scheduled for CT colonography, 33.6 % underwent CT colonography and 1.1 %
      needed a re-examination. Lesions >= 10 mm were detected in 2.9 % of the invitees.
      Invitation costs were Euro 5.57. Costs per CT colonography (intake to results)
      were Euro 144.00. Extra costs of communication of positive results were Euro
      9.00. Average costs of invitational-based CT colonography screening were Euro
      56.97 per invitee, Euro 169.40 per participant and Euro 2,772.51 per individual
      with detected advanced neoplasia. CONCLUSIONS: Dutch costs of CT-screening were
      substantially lower than the cost assumptions that were used in published cost
      effectiveness analyses on CT colonography screening. This finding indicates that
      previous cost-effectiveness analyses should be updated, at least for the Dutch
      situation.

PMID- 23138384
TI  - C-arm CT during hepatic arteriography tumour-to-liver contrast: intraindividual
      comparison of three different contrast media application protocols.
AB  - OBJECTIVE: To compare tumour-to-liver contrast (TLC) of C-arm CT during hepatic
      arteriography (CACTHA) acquired using three protocols in patients with HCC.
      METHODS: This prospective study was IRB approved and informed consent was
      obtained from each patient. Twenty-nine patients (mean age, 68 +/- 7 years; 27
      men) with 55 HCCs (mean diameter, 2.6 +/- 1.5 cm) underwent three different
      CACTHA protocols in random order before chemoembolisation. Contrast medium (100
      mg iodine/ml) was injected into the common hepatic artery (flow rate 4 ml/s). The
      imaging delay for the start of the CACTHA examination was 4 s (protocol A), 8 s
      (protocol B) and 12 s (protocol C) (total amount of injected contrast medium: 48
      ml, 64 ml, 80 ml). TLC was measured by placing regions of interest (ROIs) in the
      HCC and liver parenchyma. Mixed model ANOVAs and Bonferroni corrected post hoc
      tests were used for statistical analysis. RESULTS: Mean values for TLC were 132
      +/- 3.3 HU, 186 +/- 5.8 HU and 168 +/- 2.8 HU for protocols A, B and C. Protocol
      B provided significantly higher TLC than protocols A and C (p < 0.001).
      CONCLUSION: TLC was significantly higher using an imaging delay of 8 s compared
      with a delay of 4 or 12 s.

PMID- 23138385
TI  - Diffusion-weighted magnetic resonance imaging for staging liver fibrosis is less
      reliable in the presence of fat and iron.
AB  - OBJECTIVES: To investigate the reliability of diffusion-weighted magnetic
      resonance imaging (DW-MRI) for staging liver fibrosis in the presence of fat and
      iron. METHODS: Ninety-five patients, including 48 men and 47 women, aged 57.0 +/-
      14.2 years, underwent liver biopsy. Ninety-six samples were histologically staged
      for liver fibrosis (0-Ishak score 0; 1-Ishak score 1-4; 2-Ishak score 5-6) and
      semiquantitatively graded for hepatic iron (0, no; 1, low; 2, moderate; 3, high
      iron) and for hepatic steatosis. Within 72 h after biopsy, navigator-triggered DW
      MRI using b-values of 50/400/800 s/mm(2) was performed in a 1.5-T system, and
      apparent diffusion coefficients (ADC) were analysed. ADCs were correlated with
      fibrosis stage, steatosis grade, and iron grade using linear regression. RESULTS:
      ADC did not correlate with fibrosis stages in either the overall group (n = 96; R
      (2) = 0.38; P = 0.17) or in the subgroup without liver iron and steatosis (n =
      40; R (2) = 0.01; P = 0.75). ADC decreased significantly with steatosis grade in
      cases without iron and fibrosis (n = 42; R (2) = 0.28; beta = -5.3; P < 0.001).
      Liver iron was modestly correlated with ADC in patients without fibrosis and
      steatosis (n = 33; R (2) = 0.29; P = 0.04), whereas high iron concentrations were
      associated with low ADC values (group 3: beta = -489; P = 0.005; reference:group
      0) but intermediate levels were not (group 1/group 2: P = 0.93/P = 0.54;
      reference group: 0). CONCLUSIONS: ADC values are confounded by fat and iron.
      However, even in patients without fat or iron, DW-MRI does not adequately
      discriminate the stage of fibrosis. KEY POINTS: * Diffusion-weighted magnetic
      resonance imaging (DW-MRI) is increasingly used to evaluate liver disease. * DWI
      using b-values of 50/400/800 s/mm (2) does not adequately quantify fibrosis. *
      Assessment of the apparent diffusion coefficient (ADC) is confounded by fat and
      iron. * Fat may influence ADCs by altering water diffusion. * Iron may influence
      ADCs by signal decay and noise floor effects.

PMID- 23138386
TI  - Simulated required accuracy of image registration tools for targeting high-grade
      cancer components with prostate biopsies.
AB  - OBJECTIVES: To estimate the required spatial alignment accuracy for correctly
      grading 95 % of peripheral zone (PZ) prostate cancers using a system for
      multiparametric magnetic resonance (MR)-guided ultrasound (US) biopsies. METHODS:
      PZ prostate tumours were retrospectively annotated on multiparametric MR series
      using prostatectomy specimens as reference standard. Tumours were grouped based
      on homogeneous and heterogeneous apparent diffusion coefficient (ADC) values
      using an automated ADC texture analysis method. The proportion of heterogeneous
      tumours containing a distinct, high Gleason grade tumour focus yielding low ADC
      values was determined. Both overall tumour and high-grade focal volumes were
      calculated. All high-grade target volumes were then used in a simulated US biopsy
      system with adjustable accuracy to determine the hit rate. RESULTS: An ADC
      determined high-grade tumour focus was found in 63 % of the PZ prostate tumours.
      The focal volumes were significantly smaller than the total tumour volumes
      (median volume of 0.3 ml and 1.1 ml respectively). To correctly grade 95 % of the
      aggressive tumour components the target registration error (TRE) should be
      smaller than 1.9 mm. CONCLUSIONS: To enable finding the high Gleason grade
      component in 95 % of PZ prostate tumours with MR-guided US biopsies, a technical
      registration accuracy of 1.9 mm is required. KEY POINTS: * MRI can identify foci
      of prostatic cancer with reduced apparent diffusion coefficients * Sixty-three
      per cent of prostatic peripheral zone tumours contain high-grade tumour low ADC
      foci * The median volume of such foci is 0.3 ml * Biopsy targets are
      significantly smaller than whole tumour volumes * Simulated registration accuracy
      is 1.9 mm for correctly grading 95 % of tumours.

PMID- 23138387
TI  - Contrast-enhanced ultrasound (CEUS) follow-up after radiofrequency ablation or
      cryoablation of focal liver lesions: treated-area patterns and their changes over
      time.
AB  - OBJECTIVES: To describe the early patterns of liver lesions successfully treated
      with radiofrequency ablation (RFA) or cryoablation (CA) and their changes over
      time. METHODS: Twenty-two RFA-treated and 17 CA-treated patients underwent CEUS
      from week 1 to year 3 post-ablation. Patterns, margins and volumes of RF-induced
      and cryolesions were evaluated and compared over time. RESULTS: After contrast
      enhancement, shortly after ablation, undefined margins with persistent enhancing
      small vessels penetrating >2 mm into the treated zone were significantly more
      frequent after CA (67 %) than RFA (22 %) (P < 0.02). During the arterial phase, a
      thin, enhancing marginal rim was seen during week 1 (T1) in around 28 % of RF
      lesions, while 75 % of cryolesions had thick enhancing rims (P < 0.02). The mean
      RF-induced lesion volume, maximum at T1 (44.1 +/- 37.5 ml), shrank slowly over
      time, remaining clearly visible at 1 year (8.3 +/- 7.4 ml). Cryolesions shrank
      faster (P = 0.009), from an average of 16.6 +/- 7.1 ml at T1 to 1.7 +/- 1.3 ml 1
      year post-ablation. CONCLUSION: RF-induced and cryolesions differ, particularly
      their margins and shrinkage rates. Knowing these differences allows avoidance of
      incomplete treatment or falsely diagnosed recurrence, especially after CA. KEY
      POINTS: * Contrast-enhanced ultrasound (CEUS) provides new follow-up information
      following hepatic radiological inyervention. * CEUS provides good visualisation
      of vascular modifications after thermoablation. * RFA-induced lesions and
      cryoablated lesions differ. * Knowledge about RF and cryolesion patterns is
      essential for correct CEUS follow-up. * Cryolesions have thicker peripheral
      inflammatory reactions and shrink faster than RFA-induced lesions.

PMID- 23138388
TI  - An initial randomised study assessing free-breathing CCTA using 320-detector CT.
AB  - OBJECTIVES: To evaluate the feasibility of free-breathing coronary computed
      tomography angiography (CCTA) in adults using with a 320-detector multidetector
      CT (MDCT). METHODS: In 74 patients who underwent CCTA, 37 CCTA examinations were
      performed during free-breathing, and the remaining 37 CCTA examinations were
      produced with the standard breath-holding method. The quality scores for 16
      segments of all coronary arteries were analysed and defined as: 1 (excellent), 2
      (good), and 3 (poor). The signal-to-noise ratio (SNR), contrast-to-noise ratio
      (CNR), and effective radiation dose of each image were compared between the two
      methods. RESULTS: No significant differences were observed in the quality scores
      between the breath-holding and free-breathing methods (1.10 +/- 0.31 vs. 1.12 +/-
      0.33; P = 0.443). The SNR and CNR were not significantly different between the
      two methods. The overall mean effective radiation dose revealed no significant
      difference between the two methods (P = 0.585). CONCLUSIONS: Free-breathing CCTA
      using 320-detector MDCT showed no significant difference in image quality
      compared with standard breath-holding CCTA. For patients with difficulties of
      breath-holding or non-negligible apnoea-related heart rate variability, free
      breathing CCTA can be an alternative solution for coronary artery evaluation. KEY
      POINTS: * Cardiac CT is becoming widely used and some patients are inevitably
      breathless. * Multidetector CT (e.g. 320) offers new opportunities for the
      breathless patient. * Free breathing images yielded similar image quality to
      those obtained using breath-holding. * However, a possibility of higher radiation
      dose precludes its routine application.

PMID- 23138389
TI  - CT-guided stellate ganglion blockade vs. radiofrequency neurolysis in the
      management of refractory type I complex regional pain syndrome of the upper limb.
AB  - OBJECTIVE: To describe and evaluate the feasibility and efficacy of CT-guided
      radiofrequency neurolysis (RFN) vs. local blockade of the stellate ganglion in
      the management of chronic refractory type I complex regional pain syndrome (CRPS)
      of the upper limb. METHODS: Sixty-seven patients were included in this
      retrospective study between 2000 and 2011. All suffered from chronic upper limb
      type I CRPS refractory to conventional pain therapies. Thirty-three patients
      underwent stellate ganglion blockade and 34 benefited from radiofrequency
      neurolysis of the stellate ganglion. CT guidance was used in both groups. The
      procedure was considered effective when pain relief was >=50 %, lasting for at
      least 2 years. RESULTS: Thirty-nine women (58.2 %) and 28 men (41.8 %) with a
      mean age of 49.5 years were included in the study. Univariate analysis performed
      on the blockade and RFN groups showed a significantly (P < 0.0001) higher success
      rate in the RFN group (67.6 %, 23/34) compared with the blockade group (21.2 %,
      7/33) with an odds ratio of 7.76. CONCLUSION: CT-guided radiofrequency neurolysis
      of the stellate ganglion is a safe and successful treatment of chronic refractory
      type I CRPS of the upper limb. It appears to be more effective than stellate
      ganglion blockade. KEY POINTS: * Complex regional pain syndrome is painful,
      disabling and often refractory to treatment. * Sixty-seven percent of patients
      had lasting pain relief (2 years) after radiofrequency neurolysis. *
      Retrospective study showed a significantly higher success rate for radiofrequency
      neurolysis. * CT guidance is mandatory for a successful and safe procedure.

PMID- 23138390
TI  - Psychological factors are related to return to work among long-term sickness
      absentees who have undergone a multidisciplinary medical assessment.
AB  - OBJECTIVE: To assess the associations between psychological factors and return to
      work among long-term sickness absentees. DESIGN: Longitudinal study with a 3-year
      follow-up. SUBJECTS: Long-term sickness absentees (n = 905) who had undergone a
      multidisciplinary medical assessment. METHODS: Three years after
      multidisciplinary medical assessment, return to work status (full, partial, or
      none) was determined according to whether the individuals received full, partial,
      or no sickness benefits. Multinomial logistic regression analyses were performed
      to assess the odds ratios with 95% confidence intervals for return to work
      related to indecision, lassitude, fatigability, reduced sleep, social
      functioning, emotional role limitations, and vitality. RESULTS: After adjusting
      for socio-demographic factors and medical diagnoses most of the studied
      psychological factors were significantly associated with full (odds ratios 2.13
      1.50) and partial (odds ratios 2.25-1.63) return to work in the follow-up period.
      Low level of lassitude was associated with full return to work (odds ratio 1.72)
      even when the other psychological factors were controlled for. Similarly, low
      fatigability was associated with partial return to work (odds ratio 1.81).
      CONCLUSION: This study indicates that psychological factors are important for
      both full and partial return to work among long-term sickness absentees who have
      undergone a multidisciplinary medical assessment.

PMID- 23138392
TI  - Novel anodization technique using a block copolymer template for nanopatterning
      of titanium implant surfaces.
AB  - Precise surface nanopatterning is a promising route for predictable control of
      cellular behavior on biomedical materials. There is currently a gap in taking
      such precision engineered surfaces from the laboratory to clinically relevant
      implant materials such as titanium (Ti). In this work, anodization of Ti surfaces
      was performed in combination with block copolymer templates to create highly
      ordered and tunable oxide nanopatterns. Secondary ion mass spectroscopy (SIMS)
      and X-ray photoelectron spectroscopy (XPS) analyses showed that the composition
      of the anodized structures was mainly titania with small amounts of nitrogen left
      from the block copolymer. It was further demonstrated that these nanopatterns can
      be superimposed on more complex shaped Ti surfaces such as microbeads, using the
      same technique. Human mesenchymal stem cells were cultured on Ti microbead
      surfaces, with and without nanopatterns, in vitro to study the effect of
      nanotopography on Ti surfaces. The results presented in this work demonstrate a
      promising method of producing highly defined and well-arranged surface
      nanopatterns on Ti implant surfaces.

PMID- 23138391
TI  - Biomarkers of acute kidney injury in neonatal encephalopathy.
AB  - Acute kidney injury (AKI) is a common complication of neonatal encephalopathy
      (NE). The accurate diagnosis of neonatal AKI, irrespective of the cause, relies
      on suboptimal methods such as identification of rising serum creatinine,
      decreased urinary output and glomerular filtration rate. Studies of AKI
      biomarkers in adults and children have shown that biomarkers can improve the
      early diagnosis of AKI. Hypoxia-ischaemia is the proposed aetiological basis of
      AKI in both NE and cardiopulmonary bypass (CPB). However, there is a paucity of
      studies examining the role of AKI biomarkers specifically in NE. Urinary cystatin
      C (CysC), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18,
      kidney injury molecule-1, liver-type fatty acid-binding protein, serum CysC and
      serum NGAL all show good ability to predict early AKI in a heterogeneous
      critically ill neonatal population including infants post-CPB. Moreover, serum
      and urinary NGAL and urinary CysC are early predictors of AKI secondary to NE.
      These findings are promising and open up the possibility of biomarkers playing a
      significant role in the early diagnosis and treatment of NE-related AKI. There is
      an urgent need to explore the role of AKI biomarkers in infants with NE as
      establishing the diagnosis of AKI earlier may allow more timely intervention with
      potential for improving long-term outcome.

PMID- 23138393
TI  - EphB4 is overexpressed in gliomas and promotes the growth of glioma cells.
AB  - Glioma is one of the most common solid tumors, and the molecular mechanism for
      this disease is poorly understood. EphB4 tyrosine kinase receptor has been
      involved in various physiologic and pathologic processes, and the role of EphB4
      in tumorigenesis has recently attracted much interest. However, its function in
      glioma remains largely unknown. In this study, we explored the function of EphB4
      in glioma. We found that the expression of EphB4 was significantly upregulated in
      clinical glioma samples. Overexpression of EphB4 in glioma cell lines accelerated
      cell growth and tumorigenesis. In contrast, downregulation of EphB4 inhibited
      cell growth. Furthermore, we showed that EphB4 promoted cell growth by promoting
      EGFR signaling. Taken together, our findings suggest that EphB4 plays an
      important role in the progression of glioma by stimulating cell growth and EphB4
      might be a potential therapeutic target for glioma.

PMID- 23138394
TI  - TAGLN suppresses proliferation and invasion, and induces apoptosis of colorectal
      carcinoma cells.
AB  - In order to find the correlation between transgelin gene (TAGLN) and colorectal
      carcinoma occurrence, we investigated the expression of TAGLN in colorectal
      carcinoma tissue samples and colorectal carcinoma LoVo cells. Meanwhile, the
      effects of TAGLN on the characteristics of LoVo cells were also examined. The
      expressions of TAGLN in colorectal carcinoma tissues, adjacent normal tissues,
      and LoVo cells were detected by the Western blot method. The recombinant plasmid
      pcDNA3.1-TAGLN was established and transfected into LoVo cells with the help of
      LipofectamineTM 2000. At the same time, the TAGLN siRNA was transfected into LoVo
      cells in another group. Forty-eight hours later, the expressions of TAGLN in all
      groups were assayed by Western blot, and the cell viability was analyzed by MTT
      (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay. The cell
      cycle and cell apoptosis were examined by flow cytometry, and the cell invasive
      ability was analyzed by Transwell invasion experiment. The effect of TALGN on the
      expression of matrix metalloproteinase 9 (MMP9) was detected by Western blot.
      Western blot analysis showed that the expressions of TALGN in colorectal
      carcinoma tissues and LoVo cells were significantly decreased compared with
      colorectal carcinoma adjacent normal tissues (p < 0.01). In the overexpression or
      RNAi experiments, the plasmid pcDNA3.1-TAGLN significantly enhanced TALGN
      expression (p < 0.01), and TAGLN siRNA significantly decreased TAGLN expression
      (p < 0.01) in LoVo cells 48 h after transfection. In addition, MTT assay
      indicated that the cell viability of LoVo cells in the pcDNA3.1-TAGLN
      transfection group was significantly lower than that in the untransfected control
      group (p < 0.05). Furthermore, the overexpression of TAGLN significantly lowered
      the cell proliferation index (p < 0.05) and improved cell apoptosis (p < 0.01) in
      LoVo cells. In Transwell invasive experiments, the cell number, which had
      migrated through the chamber membrane, significantly decreased in the pcDNA3.1
      TAGLN transfection group (p < 0.05) and significantly increased in the TAGLN
      knockdown group (p < 0.05) compared to the untransfected control group. At the
      same time, the expression of MMP9 was notably inhibited in the pcDNA3.1-TAGLN
      transfection group (p < 0.01). The expressions of TAGLN were inhibited in
      colorectal carcinoma tissues and colorectal carcinoma LoVo cells. The study also
      demonstrated that TAGLN could attenuate the proliferation and invasive ability of
      LoVo cells and enhance LoVo cell apoptosis. Furthermore, the expression of MMP9
      was also inhibited by TAGLN. All these results could bring us a new perspective
      for biological therapy in colorectal carcinoma.

PMID- 23138395
TI  - Controlled fabrication of artificial ferromagnetic (Fe,Mn)3O4 nanowall-wires by a
      three-dimensional nanotemplate pulsed laser deposition method.
AB  - We have developed a new method to fabricate extremely small transition-metal
      oxide nanowires. Using a combination of nanoimprint template patterning and
      inclined substrate pulsed laser deposition, we successfully fabricated magnetic
      oxide Fe(2.5)Mn(0.5)O(4) nanowall-wires, and controlled the width in a range from
      120 nm down to about 20 nm by varying deposition parameters. Magnetoresistance
      measurements revealed ferromagnetic properties of the Fe(2.5)Mn(0.5)O(4) nanowall
      wire. This method enables the study of mesoscopic transport properties of
      transition-metal oxides towards the development of oxide-based nanodevices.

PMID- 23138396
TI  - N-acethyl-cysteine reduces the occurrence of contrast-induced acute kidney injury
      in patients with renal dysfunction: a single-center randomized controlled trial.
AB  - BACKGROUND: The occurrence of contrast-induced acute kidney injury (CIAKI) has
      paralleled the increased number of diagnostic interventions requiring
      radiographic contrast media (CM). Several strategies aimed at preventing renal
      injury following iodine have been carried out over the last several years. The
      aim of this study was to evaluate the impact of three different strategies aimed
      at preventing CIAKI in patients with renal dysfunction (serum creatinine >1.25
      mg/dl or estimated creatinine clearance <45 ml/min) receiving low osmolar CM for
      diagnostic-therapeutic procedures. METHODS: Candidates received 154 mmol NaHCO3
      solution (B0) at a rate of 3 ml/kg/h from at least 2 h before the procedure and
      at 1 ml/kg/h during and for the next 6-12 h; the same schedule plus N-acethyl
      cysteine (NAC) 600 mg twice daily the day before and the day of the procedure
      (BN) or NAC as above plus 154 mmol NaCl solution at a rate of 3 ml/kg/h from at
      least 2 h before the procedure and at 1 ml/kg/h during and for the next 6-12 h
      (SN). Serum creatinine (SCr) was measured at baseline and on days 2 or
      occasionally 3 after CM. The main outcome measure was the occurrence of CIAKI,
      defined as a >=25% increase in SCr within 2-3 days of CM. RESULTS: The three
      groups were similar with regard to age, gender distribution, weight, baseline
      serum levels of creatinine, sodium, potassium, urate and estimated creatinine
      clearance. A larger proportion of individuals received ACEIs/ARAs in the BN group
      (p < 0.05), but in the SN group, more patients declared a past history of acute
      myocardial infarction or had high blood pressure, and few displayed mild-moderate
      left ventricular dysfunction (p < 0.05). CIAKI occurred in 24/123 (19.5%)
      assessable patients (15/42 in the B0 group, 3/43 in the BN group and 6/38 in the
      SN group; p < 0.01). Thus, 15/42 patients who did not receive NAC developed CIAKI
      in contrast to 9/81 who did (p < 0.01). Multivariate logistic regression models
      showed that the use of NAC was the unique factor associated with a statistically
      significant influence for the occurrence of CIAKI (OR: 0.18; 95% CI: 0.04-0.72; p
      = 0.016). CONCLUSIONS: The results from this study show that: (1) the occurrence
      of CIAKI after low-osmolar CM administration is similar to that reported
      worldwide. (2) NAC-based renoprotective measures are superior for the prevention
      of CIAKI in patients with previous renal dysfunction. (3) They also demonstrate
      that bicarbonate expansion alone has limited value in preventing CIAKI. For those
      individuals at risk, combination prophylaxis including volume expansion plus NAC
      should be recommended to reduce the chance of overt kidney injury following CM
      administration.

PMID- 23138397
TI  - Differential expression of T-cell genes in blood and bone marrow between ITP
      patients and controls.
AB  - Primary immune thrombocytopenia (ITP) is an autoimmune disease characterised by
      premature platelet destruction in spleen, liver and bone marrow and a diminished
      production of platelets. T-cells are important in all forms of autoimmunity
      including ITP; however, very little is known about T-cells in organs where
      platelets are destroyed. Our aim was to investigate differences in gene
      expression in peripheral blood-derived T-cells and bone marrow-derived T-cells
      between ITP patients and controls. T-cells and subsequent RNA were isolated from
      blood and bone marrow from chronic ITP patients and healthy controls followed by
      DNA microarray analysis. There were 1554 differentially expressed genes in
      peripheral blood-derived T-cells and 976 in bone marrow-derived T-cells between
      ITP patients and controls and three genes were verified with real-time PCR. Using
      Gene Ontology functional enrichment analysis we found that genes involved in
      growth, development, migration, chemotaxis, adhesion and apoptosis were enriched
      in bone marrow-derived T-cells in ITP. Immune-related genes involved in T-helper
      cell differentiation, T-cell chemotaxis, migration, immunoglobulin-mediated
      immune response and classical and alternative pathway complement activation were
      also enriched in bone marrow-derived T-cells in ITP. Only 213 T-cell genes were
      differentially expressed in both blood and bone marrow between ITP patients and
      controls. In conclusion, our findings show that genes involved in major
      pathophysiologic pathways in ITP such as T-helper cell differentiation,
      autoantibody response and complement activation are altered in bone marrow
      derived T-cells in ITP patients compared with controls. This further supports the
      concept that bone marrow is an important compartment in ITP.

PMID- 23138398
TI  - Parental, fetal, and infant risk factors for preschool overweight: the Generation
      R Study.
AB  - BACKGROUND: Overweight has its origins largely in early life. We aimed to
      identify the most important parental, fetal, and infant risk factors of preschool
      overweight. METHODS: In a prospective cohort study, among 3,610 Caucasian
      preschool children, we assessed the associations of 34 putative parental, fetal,
      and infant factors with overweight risk. RESULTS: Higher maternal BMI, paternal
      BMI, and birth weight were associated with higher risk of preschool overweight
      (odds ratio (OR): 1.23, 95% confidence interval (CI): 1.10, 1.39; OR: 1.35, 95%
      CI: 1.19, 1.53; and OR: 2.71, 95% CI: 2.27, 3.25, respectively, per SD increase).
      The same model identified low household income (OR: 1.74, 95% CI: 1.24, 2.45),
      being female (OR: 1.55, 95% CI: 1.20, 2.01), and experiencing third-trimester
      accelerated growth (OR: 1.73, 95% CI: 1.24, 2.40) or postnatal accelerated growth
      (OR: 6.39, 95% CI: 4.54, 8.99) as risk factors for preschool overweight. Higher
      polyunsaturated fat intake at 14 mo was associated with a lower risk of preschool
      overweight (OR: 0.77, 95% CI: 0.62, 0.96 per SD). CONCLUSION: Parental
      anthropometrics and household income, fetal and infant accelerated growth, and
      infant dietary fat intake are the major risk factors for the development of
      preschool overweight. Further studies need to explore whether these risk factors
      could be potential targets for preventive interventions.

PMID- 23138399
TI  - Phase 1 study of two inodilators in neonates undergoing cardiovascular surgery.
AB  - BACKGROUND: Inodilators are routinely used in cardiovascular surgery with
      cardiopulmonary bypass (CPB). Information regarding safety and tolerability of
      the novel molecule, levosimendan (LEVO), in newborns is anecdotal; no
      pharmacokinetic data in this population are available. METHODS: This was a phase
      I, randomized, and blinded study. Neonates undergoing surgical repair for
      congenital heart defects received stepwise dose increases of milrinone (MR; 0.5-1
      MUg/kg/min, n = 9) or LEVO (0.1-0.2 MUg/kg/min, n = 11) as an i.v. continuous
      infusion, starting before CPB. Infants had continuous, time-locked,
      physiological, and near-infrared spectroscopy (NIRS) (cerebral and peripheral)
      recordings during the first 24 h, and at 48 and 96 h postsurgery. Serial
      biochemistry and pharmacokinetic studies were performed. RESULTS: During the
      first 24 h postsurgery, patients showed time-related, group-independent increased
      cerebral tissue oxygenation and decreased diastolic blood pressure; in addition,
      group-dependent differences in heart rate and peripheral perfusion were found.
      Early postsurgery, MR-treated infants showed lower pH, higher glycemia, and
      higher inotrope score. The groups differed in cerebral NIRS-derived variables
      from 24 to 96 h. Study drug withdrawal at 96 h was more frequent with LEVO. LEVO
      intermediate metabolites were detected in plasma at day 14 after surgery.
      CONCLUSION: LEVO is well tolerated in critically ill neonates. LEVO may have
      advantages over MR in terms of the dosing regimen.

PMID- 23138400
TI  - Antiepileptic effects of levetiracetam in a rodent neonatal seizure model.
AB  - BACKGROUND: Neonatal seizures can result in chronic epilepsy and long-term
      behavioral and cognitive deficits. Levetiracetam (LEV), an antiepileptic drug
      that binds to the synaptic vesicle protein 2A (SV2A), has been increasingly used
      off-label for the therapy of neonatal seizures. Preclinical data regarding the
      acute or long-term efficacy of LEV are lacking. METHODS: We tested the
      anticonvulsant efficacy of LEV in a rat model of hypoxia-induced neonatal
      seizures. In addition, we evaluated the protective effects of postnatal day (P)10
      LEV treatment on later-life kainic acid (KA)-induced seizure susceptibility and
      seizure-induced neuronal injury. Western blot and immunohistochemistry were used
      to assess the developmental regulation of SV2A in the rat and human brain.
      RESULTS: LEV pretreatment at P10 significantly decreased the cumulative duration
      of behavioral and electrographic seizures at both 25 and 50 mg/kg. At P40, KA
      induced seizures and neuronal loss were significantly diminished in rats
      previously treated with LEV. LEV target SV2A is present in both neonatal rat and
      human brain and increases steadily to adulthood. CONCLUSION: LEV suppressed acute
      seizures induced by perinatal hypoxia and diminished later-life seizure
      susceptibility and seizure-induced neuronal injury, providing evidence for
      disease modification. These results support consideration of a clinical trial of
      LEV in neonatal seizures.

PMID- 23138401
TI  - Long-term reparative effects of mesenchymal stem cell therapy following neonatal
      hyperoxia-induced lung injury.
AB  - BACKGROUND: Mesenchymal stem cell (MSC) therapy may prevent neonatal hyperoxia
      induced lung injury (HILI). There are, however, no clear data on the therapeutic
      efficacy of MSC therapy in established HILI, the duration of the reparative
      effects, and the exact mechanisms of repair. The main objective of this study was
      to evaluate whether the long-term reparative effects of a single intratracheal
      (IT) dose of MSCs or MSC-conditioned medium (CM) are comparable in established
      HILI. METHODS: Newborn rats exposed to normoxia or hyperoxia from postnatal day
      (P)2)-P16 were randomized to receive IT MSCs, IT CM, or IT placebo (PL) on P9.
      Alveolarization and angiogenesis were evaluated at P16, P30, and P100. RESULTS:
      At all time periods, there were marked improvements in alveolar and vascular
      development in hyperoxic pups treated with MSCs or CM as compared with PL. This
      was associated with decreased expression of inflammatory mediators and an
      upregulation of angiogenic factors. Of note, at P100, the improvements were more
      substantial with MSCs as compared with CM. CONCLUSION: These data suggest that
      acute effects of MSC therapy in HILI are mainly paracrine mediated; however,
      optimum long-term improvement following HILI requires treatment with the MSCs
      themselves or potentially repetitive administration of CM.

PMID- 23138403
TI  - Thoracic elongation in type III osteogenesis imperfecta patients with thoracic
      insufficiency syndrome.
AB  - STUDY DESIGN: Prospective patient series. OBJECTIVE: To evaluate outcome of
      children experiencing severe osteogenesis imperfecta (OI) with thoracic
      insufficiency syndrome (TIS), who were treated with a novel expandable
      spinothoracic fixation device. SUMMARY OF BACKGROUND DATA: Current treatment
      options for TIS in patients with OI are limited. As in other patients with TIS,
      thoracic elongation is the treatment of choice; however, the use of vertical
      expandable prosthetic titanium rib device is contraindicated for patients with
      poor bone quality. METHODS: From 2007 to 2009, 4 patients with type III OI with
      TIS, aged 8 to 12 years, were treated with a novel expandable spinothoracic
      fixation device. Pre- and postoperative mobility, Cobb angle, PO2, PCO2, forced
      vital capacity, forced expiratory flow, use of accessory muscles when breathing,
      body weight, complication rates, and patient satisfaction were assessed. RESULTS:
      Prior to surgery, 2 patients were wheelchair bound and 2 walked with assistive
      devices. Average follow-up was 24 months (range, 14-36 mo). Mean Cobb angle
      improved by up to 32% in the coronal plane. Pulmonary function improved in all
      patients, with mean increases of 45% in forced vital capacity, 93% in forced
      expiratory flow, and 43% in PO2. PCO2 declined 30% on average, returning to
      normal values. Mean patient weight at 6-month follow-up increased by 10.9%.
      Patients moved from less than 3rd weight percentile per age group to the 3rd to
      7th percentiles at the 6-month follow-up, with continuing weight gain. There were
      no major complications. All patients and their caregivers were satisfied that the
      procedure led to improved self-image and functional level. CONCLUSION: Thoracic
      elongation improved pulmonary function, facilitated weight gain, and made an
      indirect correction of spinal deformities (Cobb angle) by more than 30%, with no
      significant complications. Because of the rarity of this condition, a multicenter
      study to gain experience in a larger number of patients is recommended.

PMID- 23138402
TI  - Predictive monitoring for respiratory decompensation leading to urgent unplanned
      intubation in the neonatal intensive care unit.
AB  - BACKGROUND: Infants admitted to the neonatal intensive care unit (NICU), and
      especially those born with very low birth weight (VLBW; <1,500 g), are at risk
      for respiratory decompensation requiring endotracheal intubation and mechanical
      ventilation. Intubation and mechanical ventilation are associated with increased
      morbidity, particularly in urgent unplanned cases. METHODS: We tested the
      hypothesis that the systemic response associated with respiratory decompensation
      can be detected from physiological monitoring and that statistical models of
      bedside monitoring data can identify infants at increased risk of urgent
      unplanned intubation. We studied 287 VLBW infants consecutively admitted to our
      NICU and found 96 events in 51 patients, excluding intubations occurring within
      12 h of a previous extubation. RESULTS: In order of importance in a multivariable
      statistical model, we found that the characteristics of reduced O(2) saturation,
      especially as heart rate was falling; increased heart rate correlation with
      respiratory rate; and the amount of apnea were all significant independent
      predictors. The predictive model, validated internally by bootstrap, had a
      receiver-operating characteristic area of 0.84 +/- 0.04. CONCLUSION: We propose
      that predictive monitoring in the NICU for urgent unplanned intubation may
      improve outcomes by allowing clinicians to intervene noninvasively before
      intubation is required.

PMID- 23138404
TI  - Development of an expectations survey for patients undergoing cervical spine
      surgery.
AB  - STUDY DESIGN: Cross-sectional analysis of patient-reported preoperative data.
      OBJECTIVE: To develop a valid and reliable patient-derived expectations survey
      for patients undergoing cervical spine surgery. SUMMARY OF BACKGROUND DATA:
      Measuring expectations is an important component in the assessment of patients
      undergoing cervical spine surgery. However, there currently are no uniform
      methods to measure expectations. METHODS: This study was conducted in 3 phases.
      In phase 1, patients were queried with open-ended questions about what they
      expected as a result of surgery. Their responses were grouped into categories
      that became the items in the draft survey. During phase 2, another group of
      patients completed the draft survey twice to establish test-retest reliability.
      In phase 3, items were selected on the basis of concordance and clinical
      relevance and a scoring rubric was developed. RESULTS: Phase 1: 25 patients with
      radiculopathy, myelopathy, or previous surgery with failed fusion (nonunion)
      (mean age, 55 yr, 44% women) volunteered 114 expectations from which 31
      categories were discerned and became the items in the draft survey. Phase 2:
      another 25 patients completed the survey twice before surgery, a mean of 5 days
      apart. Phase 3: 21 items were retained for the final survey addressing pain,
      numbness, physical limitations, and psychological well-being. An overall score
      can be calculated ranging from 0 to 100 that incorporates number of items
      expected and degree of improvement expected. For patients in phase 2, scores for
      the first and second administrations were 58 and 57, Cronbach alpha coefficients
      were 0.90 and 0.93, and the intraclass correlation coefficient between scores was
      0.90. CONCLUSION: We developed a valid and reliable patient-derived expectations
      survey for patients undergoing cervical spine surgery that addresses expectations
      for physical and psychological well-being and generates an easy-to-interpret
      overall score. The survey can be used clinically and for research and fills a gap
      in the comprehensive preoperative assessment of patients undergoing cervical
      spine surgery.

PMID- 23138405
TI  - The effect of required physiatrist consultation on surgery rates for back pain.
AB  - STUDY DESIGN: Prospective trial with insurance database and surveys. OBJECTIVE:
      This study was developed to determine whether an insurer rule requiring
      physiatrist consultation before nonurgent surgical consultation would affect
      surgery referrals and surgery rates. SUMMARY OF BACKGROUND DATA: Spine surgery
      rates are highly variable by region and increasing without evidence of a
      concordant decrease in the burden of disease. Efforts to curb misuse of surgery
      have not shown large changes, especially across different provider groups. As
      nonsurgical spine experts, physiatrists might provide patients with a different
      perspective on treatment options. METHODS: In 2007, the insurer required patients
      with nonurgent spine surgical consultations in a geographic region to first have
      a single visit with a physiatrist, who received extra compensation for the
      assessment. Surgical consultation and surgical rates results were compared
      between 2006-2007 and 2008-2010. An automated telephone survey of patients
      evaluated by physiatrists was performed to assess patient satisfaction. RESULTS:
      Physiatry referrals increased 70%, surgical referrals decreased 48%, and the
      total number of spine operations dropped 25%, with concomitant decreased overall
      cost. Although spinal fusion rates dropped, the percentage of fusion operations
      increased from 55% to 63% of all surgical procedures. Of 740 patients surveyed
      (48% response rate), 74% were satisfied or very satisfied with the physiatry
      consultation. Only 40% of patients who underwent previous spine surgery were
      satisfied. Although surgical rates decreased at all regional hospitals and all
      surgical groups, there were substantial shifts in market share. CONCLUSION:
      Mandatory physiatrist consultation prior to surgical consultation resulted in
      decreased surgical rates and continued patient satisfaction across a large
      region.

PMID- 23138406
TI  - Effect of hyperbaric oxygenation on intervertebral disc degeneration: an in vivo
      study with sprague-dawley rats.
AB  - STUDY DESIGN: An in vivo study was conducted to test the effect of hyperbaric
      oxygenation (HBO) on intervertebral disc degeneration in Sprague-Dawley rats.
      OBJECTIVE: To observe the changes in intervertebral disc height and levels of
      glycosaminoglycan, collagen, interleukin-1beta (IL-1beta), prostaglandin E2
      (PGE2), and inducible nitric oxide synthase (iNOS) in degenerated intervertebral
      discs after HBO therapy. SUMMARY OF BACKGROUND DATA: Although the involvement of
      IL-1beta, PGE-2, NO, and low O2 concentration has been demonstrated in
      intervertebral disc degeneration, the actual mechanism is not clear. It has been
      reported that HBO influences changes in IL-1beta, PGE-2, NO, and O2
      concentration. Previously, a study demonstrated an in vitro positive effect of
      HBO on the human nucleus pulposus. Thus, an in vivo study in animals was
      necessary. METHODS: Twelve Sprague-Dawley rats were each injected with
      chondroitinase ABC in 2 proximal intervertebral discs of the tail. After treating
      with 100% oxygen at 2.5 atmospheres 2 hours per days for 10 days, the change in
      disc height was determined by radiography. The amounts of PGE-2, iNOS,
      glycosaminoglycan, and total collagen in the intervertebral disc were quantified
      by enzyme-linked immunosorbent assay. Tissue morphology and the distribution of
      glycosaminoglycan, IL-1beta, and iNOS in the intervertebral disc were assessed by
      histology and immunohistochemistry. The area of IL-1beta in the intervertebral
      discs was quantified using image analysis software. RESULTS: HBO therapy stopped
      the decrease in intervertebral disc height, caused an increase in the amount of
      glycosaminoglycan, and inhibited IL-1beta, PGE-2, and iNOS production.
      CONCLUSION: HBO provides a potential treatment modality for intervertebral disc
      degeneration.

PMID- 23138407
TI  - In response.

PMID- 23138408
TI  - Three-column osteotomies in the treatment of spinal deformity in adult patients
      60 years old and older: outcome and complications.
AB  - STUDY DESIGN: Retrospective review. OBJECTIVE: To report and analyze the
      perioperative complications, radiographical results, and functional outcomes in
      elderly patients undergoing pedicle subtraction osteotomy (PSO) and/or vertebral
      column resection (VCR) procedures for spinal deformity correction. SUMMARY OF
      BACKGROUND DATA: To our knowledge, no studies have focused on 3-column
      osteotomies in the elderly. METHODS: We retrospectively reviewed prospectively
      collected data for 51 consecutive patients 60 years or older undergoing 3-column
      osteotomies for spinal deformity correction (PSO, 36 patients; VCR, 13 patients;
      PSO and VCR, 2 patients) and who had at least 2 years' follow-up. We analyzed the
      perioperative complications; the preoperative, postoperative, and final follow-up
      radiographical measurements; and the preoperative, postoperative, and final
      follow-up functional outcome scores (using the Scoliosis Research Society-22
      questionnaire and Oswestry Disability Index). Hotelling's t2 test and the chi2
      test were used for analysis (statistical significance, P < 0.05). RESULTS: There
      were 9 (18%) major complications (5 with PSO and 4 with VCR) and 20 (39%) minor
      complications (14 with PSO and 6 with VCR). Compared with preoperative values,
      improvement at 6 weeks after surgery averaged 16 degrees  (range, 0 degrees -42
      degrees ) in thoracic scoliosis, 14 degrees  (range, 2 degrees -25 degrees ) in
      lumbar scoliosis, 9 degrees  (range, 5 degrees -35 degrees ) in thoracic
      kyphosis, -24 degrees  (range, -12 degrees  to -68 degrees ) in lumbar lordosis,
      2.4 cm (range, 0-12 cm) in coronal balance, and 6.9 cm (range, -2 to 20 cm) in
      sagittal balance. At final follow-up, improvements in the coronal and sagittal
      balance were maintained. By final follow-up, compared with preoperative state,
      there were significant improvements in all 5 Scoliosis Research Society-22
      domains and in the Oswestry Disability Index. CONCLUSION: In the elderly patient,
      PSO and VCR can achieve significant restoration of sagittal and coronal balance
      and significant improvement in quality of life. However, both techniques can lead
      to serious complications and should be selectively used.

PMID- 23138409
TI  - Why not use your own body weight to prevent falls? A randomized, controlled trial
      of balance therapy to prevent falls and fractures for elderly people who can
      stand on one leg for <=15 s.
AB  - BACKGROUND: Maintaining or improving motor (balance) ability is essential to
      extending the healthy lifespan of elderly people, and developing effective and
      efficient strategies to prevent falls of elderly people is an urgent. The purpose
      of this study was to determine the effects of balance exercise on fall and
      fracture prevention for elderly people with poor balance. METHODS: A 6-month,
      randomized controlled trial was conducted to verify whether one-leg standing with
      eyes open for a total of 1 min, three times a day (dynamic flamingo exercise)
      prevents falls and fractures. Setting and participants were elderly people >=75
      years of age and one-leg standing time <=15.0 s living in their own home. They
      were visiting orthopaedic clinics for orthopaedic handicaps. Subjects with poor
      balance were allowed to hold on to something. If a subject's lifted leg touched
      the ground during the exercise, they were allowed to lift it again and continue
      so that they stood on one leg for a total of 60 s. RESULTS: The dynamic flamingo
      exercise group (410 people; 86 men, 324 women) and the no exercise group (455
      people; 78 men, 377 women) were compared. After dynamic flamingo exercise for 6
      months, significant differences were seen in the increase in one-leg standing
      time with eyes open (men right/left, women right/left), in the improvement in
      independence in daily living (women), number of people who fell during the 6
      months (women), and adverse events (women). The number of fractures was not
      significantly different for men or women. CONCLUSIONS: Dynamic flamingo exercise
      prevents falls but no significant difference was demonstrated in fracture
      prevention in elderly women with poor balance.

PMID- 23138410
TI  - Comment on "Treating highly charged carbon and fullerene clusters as dielectric
      particles" by A. J. Stace and E. Bichoutskaia, Phys. Chem. Chem. Phys., 2011, 13,
      18339.

PMID- 23138411
TI  - Synthesis, optoelectronic properties of a dinuclear platinum(II) complex
      containing a binary cyclometalated ligand in the single-emissive-layer PLEDs.
AB  - A novel dinuclear platinum complex of (dfppy-mhb-dfppy)Pt(2)(acac)(2) was
      synthesized and characterized, where dfppy-mhb-dfppy is a binary C^N
      cyclometalated ligand containing two bridged 2,4-difluorophenylpyridine (dfppy)
      units and acac is 2,4-pentanedione anion. Compared to previously reported
      dinuclear platinum complexes with a binary ancillary ligand, this dinuclear
      platinum complex showed more intense excimer emission, peaking at 617 nm, besides
      its intrinsic emission in dilute dichloromethane solution. Single-emissive-layer
      (SEL) polymer light-emitting devices (PLEDs) using (dfppy-mhb
      dfppy)Pt(2)(acac)(2) as dopant and a blend of poly (N-vinylcarbazole) (PVK) and 2
      (4-biphenyl)-5-(4-tert-butylphenyl)-1,3,4-oxadiazole (PBD) as host matrix
      exhibited stable white emission at 1 wt% doping concentration under applied
      voltages from 7 V to 11 V. The stable white emission observed in the (dfppy-mhb
      dfppy)Pt(2)(acac)(2)-doped SEL PLEDs indeed implies that the dinuclear platinum
      complex constructed by a binary cyclometalated ligand has a potential application
      in white-emitting SEL PLEDs.

PMID- 23138412
TI  - A three-week multidisciplinary in-patient rehabilitation programme had positive
      long-term effects in patients with ankylosing spondylitis: randomized controlled
      trial.
AB  - OBJECTIVE: To evaluate the mean overall effects over a 1-year period of a
      multidisciplinary in-patient rehabilitation programme for patients with
      ankylosing spondylitis. DESIGN: Observer-blinded, randomized controlled trial,
      with assessments made after 4 and 12 months. PATIENTS: Forty-six patients
      received a 3-week in-patient rehabilitation programme and 49 patients received
      treatment as usual. METHODS: Primary outcomes were disease activity measured with
      the Bath Ankylosing Spondylitis Disease Activity Scale (BASDAI), and function
      measured with the Bath Ankylosing Spondylitis Functional Index (BASFI). Secondary
      outcomes included well-being, spinal and hip mobility, and health-related quality
      of life measured with the Medical Outcome Study Short Form-36. Overall treatment
      effects were estimated with Mixed models repeated measures analyses. RESULTS:
      Significant overall treatment effects in favour of the rehabilitation group were
      found in the BASDAI score (mean difference over the 1-year period -10.0, 95%
      confidence interval: -3.7 to -16.3), in well-being (-7.3, 95% confidence
      interval: -1.0 to -14.7), and in the Medical Outcome Study Short Form-36
      variables social functioning, role physical, role mental and bodily pain (mean
      differences ranging from 5.8 (pain) to 10.7 (role physical)). CONCLUSION: A 3
      week in-patient rehabilitation programme had positive overall effects on disease
      activity, pain, function and well-being, and should be considered an important
      complement to medical disease management in persons with ankylosing spondylitis.

PMID- 23138413
TI  - The survey of porcine teschoviruses in field samples in China with a universal
      rapid probe real-time RT-PCR assay.
AB  - A real-time reverse transcription polymerase chain reaction (RT-PCR) based on
      TaqMan was established and evaluated for quantitative detection of porcine
      teschoviruses (PTVs). A pair of primers and a TaqMan probe targeting on the
      highly conserved sequence of the 5'-untranslated region (5'-UTR) of one to 11
      serotypes of PTV were designed. Standard plasmid DNA containing PCR amplification
      of the 5'-UTR were constructed and used to develop the real-time RT-PCR. The
      results indicated that the real-time RT-PCR was specific for detection of PTV
      with a detection limit of 10 copies/MUL, but not for porcine parvovirus, porcine
      circovirus type 2, porcine reproductive and respiratory syndrome virus,
      pseudorabies virus, classical swine fever virus. The coefficient of variation of
      inter-assay and intra-assay were less than 3 %. A total of 91 clinical samples
      were tested by the real-time RT-PCR and virus isolation (OIE 2008) and positive
      rates were 79.12 % (72/91) and 57.14 % (48/91), respectively. In conclusion, the
      developed real-time RT-PCR assay was an effective method for detection and
      quantification of PTV in fields or organs of infected pigs.

PMID- 23138414
TI  - Human herpes virus type 6 can cause skin lesions at the BCG inoculation site
      similar to Kawasaki Disease.
AB  - Kawasaki Disease (KD) is acute, febrile, multisystem vasculitis of early
      childhood, the detailed mechanism of which is still unclear.  Skin symptoms occur
      in KD, such as edema of the hands and feet with subsequent desquamation and
      redness at the inoculation site of bacillus Calmette-Guerin (BCG).  The change at
      the BCG inoculation site has been considered as a specific feature of KD,
      although its mechanism is not fully understood.  We present an 11-month-old boy
      who developed fever with redness of the BCG site due to infection with human
      herpes virus type 6 (HHV6).  At the age of 3 months, the patient received BCG. 
      His fever remitted 7 days after the onset of skin redness, with sequential
      desquamation at the BCG site and extremities, which is not a common feature of
      HHV6 infection that typically lasts for 3 days.  The final diagnosis was
      exanthema subitum.  Characteristically, the HHV6 infection in our patient
      appeared to be associated with the invigoration of the T cell system, as
      represented by the elevated serum levels of soluble interleukin-2 receptor (3,490
      U/ml vs.  normal range 145-519 U/ml).  This patient clearly showed redness and
      crusting at the BCG inoculation site, suggesting that HHV6 infection might cause
      skin changes similar to those of KD via an unknown mechanism.  In addition, we
      suggest that the activation of the T cell system may account for the skin lesions
      in KD, characterized by redness and subsequent crusting of the BCG inoculation
      site and desquamation of the extremities.

PMID- 23138415
TI  - Synthesis of transfer-free graphene on an insulating substrate using a solid
      phase reaction.
AB  - We demonstrate a solid phase reaction approach to synthesise transfer-free
      graphene on an insulating substrate by controlling the C diffusion process. Metal
      assisted crystallization by annealing of a C thin film was carried out to
      synthesise transfer-free graphene, in the presence of a top metal oxide and metal
      layer. Without the metal oxide layer, a large amount of C atoms diffused to the
      top of the metal surface and hence the formation of only small graphene domains
      was observed on the underneath of the metal layer. Introducing the metal oxide
      layer at the top surface, C diffusion was reduced and consequently the thin C
      film was crystallized to form large area graphene at the metal-insulating
      substrate interface. The metal oxide or metal catalyst layer was removed after
      graphene formation and transfer-free graphene was obtained directly on the base
      substrate. This finding shows that the thin metal oxide layer is critical to
      synthesise graphene with better quality and continuous domain structures.

PMID- 23138416
TI  - Polycyclic aromatic hydrocarbons in soils from Urumqi, China: distribution,
      source contributions, and potential health risks.
AB  - Concentrations of 16 priority polycyclic aromatic hydrocarbons (PAHs) were
      measured in 28 surface soils samples collected from Urumqi, northwest China, for
      examination of distributions, source contributions, and potential health effects.
      The results indicated that the sum of 16 PAHs concentration ranged from 331 to
      15,799 MUg kg(-1) (dw) in soils, with a mean of 5,018 +/- 4,896 MUg kg(-1) (n =
      28). The sum of seven carPAHs concentration ranged from 4 to 1,879 MUg kg(-1)
      (dw; n = 28). The highest ?PAHs concentrations were found at roadsides and
      industrial sites, followed by those at parks, rural areas, and
      business/residential areas. Coal combustion, emission of diesel and gasoline from
      vehicles, and petroleum source were four sources of PAHs as determined by PMF
      analysis, which contributed 51.19, 19.02, 18.35, and 11.42% to the PAH sources,
      respectively. Excellent coefficients of correlation between the measured and
      predicted PAHs concentrations suggested that the PMF model was very effective to
      estimate sources of PAHs in soils. Incremental lifetime cancer risk values at the
      95th percentile due to human exposure to surface soils PAHs in Urumqi were 2.02 *
      10(-6) for children and 2.72 * 10(-5) for adults. The results suggested that the
      current PAHs levels in soils from Urumqi were pervasive and moderately
      carcinogenic to children and adults.

PMID- 23138417
TI  - Five-year monitoring study of chemical characteristics of Wet atmospheric
      precipitation in the southern region of Jordan.
AB  - Wet atmospheric samples were collected from different locations in the southern
      region of Jordan during a 5-year period (October 2006 to May 2011). All samples
      were analyzed for pH, EC, major ions (Ca(2+), Mg(2+), Na(+), K(+), HCO3(-), Cl(
      ), NO3(-), and SO4(2-)), and trace metals (Fe(2+), Al(3+), Cu(2+), Pb(2+), and
      Zn(2+)). The highest ion concentrations were observed during the beginning of the
      rainfall events because large amounts of dust accumulated in the atmosphere
      during dry periods and were scavenged by rain. The rainwater in the study area is
      characterized by low salinity and neutral pH. The major ions found in rainwater
      followed the order of HCO3  >  Cl(-) >  SO4(2-) and Ca(2+) >  Na(+) > Mg(2+) >
      NH4(+) > K(+). Trace metals were identified to be of anthropogenic origin
      resulting from cement and phosphate mining activities located within the
      investigated area and from heating activities during the cold period of the year
      (January to April). The wet precipitation chemistry was analyzed using factor
      component analysis for possible sources of the measured species. Factor analysis
      (principal component analysis) was used to assess the relationships between the
      concentrations of the studied ions and their sources. Factor 1 represents the
      contribution of ions from local anthropogenic activities, factor 2 represents the
      contribution of ions from natural sources, and factor 3 suggests biomass burning
      and anthropogenic source. Overall, the results revealed that rainwater chemistry
      is strongly influenced by local anthropogenic sources rather than natural and
      marine sources, which is in a good agreement with the results obtained by other
      studies conducted in similar sites around the world.

PMID- 23138418
TI  - Reference values for heavy metals in soils of the Brazilian agricultural frontier
      in Southwestern Amazonia.
AB  - Guideline values are used to identify polluted or contaminated areas based on
      background values. Brazilian law establishes three guideline values for
      pollutants: a quality reference value (QRV), a prevention value, and an
      intervention value. Reference values refer to the natural concentration of an
      element or a substance in soils that have not been modified by anthropogenic
      impacts. These values inform assessments of soil quality and are used to
      establish maximum permissible limits. The objective of this study was to
      determine the natural levels and reference values for Cd, Co, Cr, Cu, Ni, Pb, and
      Zn in samples from the surface layer (0-20 cm) of 19 representative soils of the
      states of Mato Grosso and Rondonia, on Brazil's agricultural frontier. Pseudo
      total metal concentrations were obtained following microwave-assisted digestion
      using the aqua regia and EPA3051 methods. QRVs were calculated for each element
      as the 75th and 90th percentiles of the frequency distribution of the data.
      Natural levels of heavy metals in the soil samples followed the order: Cr > Zn >
      Cu > Co > Pb > Ni > and Cd (aqua regia) and Cr > Co > Cu > Pb > Zn > Ni > Cd
      (EPA3051). These values are generally lower than those reported in the Brazilian
      and international literature, which highlights the importance of establishing
      reference values for each state or for each soil type, taking into account the
      geomorphological, pedological, and geological diversity of the region under
      study.

PMID- 23138419
TI  - Cytogenetic evaluation and the association with polymorphisms of the CPY1A1 and
      NR1I3 genes in individuals exposed to BTEX.
AB  - The gas station attendants are exposed daily to chemical agents that compose
      gasoline, such as BTEX (benzene, toluene, ethylbenzene, and xylene), and the
      exposure to these agents can cause a variety of effects on the human health.
      Among the various possible cell alterations associated with these exposures are
      the formation of micronuclei and of binucleated cells which are used as
      indicators of clastogenic action. Benzene, the main carcinogenic agent, is
      metabolized to more soluble forms and easily excreted by isoenzymes of cytochrome
      P450, such as CYP1A1. The CYP1A1 gene is highly polymorphic and one of its allele
      variations can be detected by the use of restriction endonucleasis MspI and is
      originated by the transition of a thymine by a cytosine (3798T>C), resulting in
      the polymorphic allele CYP1A1*2A. The objective of this study was to evaluate the
      cytogenetic damage induced by the exposure to BTEX and to associate it with the
      polymorphisms of the CYP1A1 and NR1I3 genes. Samples of exfoliated cells from the
      oral mucosa of 27 gas station attendants and from a control group were collected.
      The results found show that the group exposed to BTEX presents significantly
      higher alterations than those in the control group for micronuclei (MN; 6.85 +/-
      1.33 vs. 2.96 +/- 1.91, P < 0.001) and for the total of nuclear alterations
      observed (MN + binucleated cells (BNC); 9.59 +/- 4.73 vs. 5.07 +/- 2.21, P <
      0.001). When comparing the cytological alterations and the genotypes among the
      exposed individuals for the polymorphism 3798T>C of the CYP1A1 gene, homozygotes
      TT present MN + BNC significantly higher than carriers of the allele C (10.88 +/-
      5.36 vs. 5.33 +/- 2.52, P = 0.028). No association was observed in the control
      group or for the NR1I3 gene. These results show that molecular and cytogenetic
      data can be used in the future as tools to monitor individuals exposed to such
      compounds.

PMID- 23138420
TI  - Accuracy of emergency physician-performed ultrasonography in the diagnosis of
      deep-vein thrombosis: a systematic review and meta-analysis.
AB  - Duplex ultrasound is the first-line diagnostic test for detecting lower limb deep
      vein thrombosis (DVT) but it is time consuming, requires patient transport, and
      cannot be interpreted by most physicians. The accuracy of emergency physician
      performed ultrasound (EPPU) for the diagnosis of DVT, when performed at the
      bedside, is unclear. We did a systematic review and meta-analysis of the
      literature, aiming to provide reliable data on the accuracy of EPPU in the
      diagnosis of DVT. The MEDLINE and EMBASE databases (up to August 2012) were
      systematically searched for studies evaluating the accuracy of EPPU compared to
      either colour-flow duplex ultrasound performed by a radiology department or
      vascular laboratory, or to angiography, in the diagnosis of DVT. Weighted mean
      sensitivity and specificity and associated 95% confidence intervals (CIs) were
      calculated using a bivariate random-effects regression approach. There were 16
      studies included, with 2,379 patients. The pooled prevalence of DVT was 23.1%
      (498 in 2,379 patients), ranging from 7.4% to 47.3%. Using the bivariate
      approach, the weighted mean sensitivity of EPPU compared to the reference imaging
      test was 96.1% (95%CI 90.6-98.5%), and with a weighted mean specificity of 96.8%
      (95%CI:94.6-98.1%). Our findings suggest that EPPU may be useful in the
      management of patients with suspected DVT. Future prospective studies are
      warranted to confirm these findings.

PMID- 23138422
TI  - The utility of basic animal research.

PMID- 23138423
TI  - Accept no substitutes: the ethics of alternatives.

PMID- 23138424
TI  - Training the next generation.

PMID- 23138425
TI  - Progress in the animal research war.

PMID- 23138426
TI  - No animals harmed: toward a paradigm shift in toxicity testing.

PMID- 23138427
TI  - Raising the bar: the implications of the IOM report on the use of chimpanzees in
      research.

PMID- 23138428
TI  - The case for phasing out experiments on primates.

PMID- 23138429
TI  - U.S. law and animal experimentation: a critical primer.

PMID- 23138430
TI  - The moral status of invasive animal research.

PMID- 23138432
TI  - Using monkeys to understand and cure Parkinson disease.

PMID- 23138433
TI  - Cariprazine (RGH-188), a D3-preferring dopamine D3/D2 receptor partial agonist
      antipsychotic candidate demonstrates anti-abuse potential in rats.
AB  - RATIONALE: Cariprazine (RGH-188) is a D3-preferring dopamine D3/D2 receptor
      partial agonist antipsychotic candidate for the treatment of schizophrenia and
      bipolar mania. Substance abuse is a frequent comorbidity of both disorders and is
      associated with serious health issues. Based on preclinical efficacy, dopamine D2
      and D3 receptor partial agonists and antagonists are assumed to have relapse
      preventing potential in human cocaine addiction. OBJECTIVES: We investigated the
      anti-abuse potential of cariprazine in cocaine self-administration paradigms.
      Aripiprazole and bifeprunox were used as comparators because of their
      pharmacological similarity to cariprazine. METHODS: The effects of compounds on
      cocaine's rewarding effect were investigated in a continuous self-administration
      regimen. The relapse-preventing potential of drugs was studied in rats with a
      history of cocaine self-administration after a period of complete abstinence in a
      relapse to cocaine-seeking paradigm. RESULTS: Cariprazine, as well as
      aripiprazole and bifeprunox, were able to reduce the rewarding effect of cocaine
      (minimum effective doses were 0.17, 1, and 0.1 mg/kg, respectively) and
      attenuated relapse to cocaine seeking with half maximal effective dose [ED50]
      values of 0.2, 4.2, and 0.17 mg/kg, respectively. CONCLUSIONS: These results may
      predict a relapse-preventing action for cariprazine in humans in addition to its
      already established antipsychotic and antimanic efficacy.

PMID- 23138434
TI  - Impulsivity, attention, memory, and decision-making among adolescent marijuana
      users.
AB  - RATIONALE: Marijuana is a popular drug of abuse among adolescents, and they may
      be uniquely vulnerable to resulting cognitive and behavioral impairments.
      Previous studies have found impairments among adolescent marijuana users.
      However, the majority of this research has examined measures individually rather
      than multiple domains in a single cohesive analysis. This study used a logistic
      regression model that combines performance on a range of tasks to identify which
      measures were most altered among adolescent marijuana users. OBJECTIVES: The
      purpose of this research was to determine unique associations between adolescent
      marijuana use and performances on multiple cognitive and behavioral domains
      (attention, memory, decision-making, and impulsivity) in 14- to 17-year-olds
      while simultaneously controlling for performances across the measures to
      determine which measures most strongly distinguish marijuana users from nonusers.
      METHODS: Marijuana-using adolescents (n = 45) and controls (n = 48) were tested.
      Logistic regression analyses were conducted to test for: (1) differences between
      marijuana users and nonusers on each measure, (2) associations between marijuana
      use and each measure after controlling for the other measures, and (3) the degree
      to which (1) and (2) together elucidated differences among marijuana users and
      nonusers. RESULTS: Of all the cognitive and behavioral domains tested, impaired
      short-term recall memory and consequence sensitivity impulsivity were associated
      with marijuana use after controlling for performances across all measures.
      CONCLUSIONS: This study extends previous findings by identifying cognitive and
      behavioral impairments most strongly associated with adolescent marijuana users.
      These specific deficits are potential targets of intervention for this at-risk
      population.

PMID- 23138435
TI  - In spina bifida aperta, muscle ultrasound can quantify the "second hit of
      damage".
AB  - PURPOSE: In spina bifida aperta (SBA), the "second-hit hypothesis" addresses
      consequences by delayed neurological damage superimposed upon the congenital
      myelomeningocele (MMC). This secondary damage is postulated to underlie the
      disappearance of leg movements shortly after birth. Innovative fetal surgery
      might prevent this, but results are methodologically hard to prove in small and
      heterogeneous treatment groups. We reasoned that delayed postnatal alterations in
      muscle ultrasound density (MUD = muscle echogenicity) could quantitatively
      reflect consequences by "the second hit" of damage. In the present study, we
      investigated whether delayed postnatal leg-MUD alterations are associated with
      postnatal muscle function loss. METHODS: We cross-sectionally assessed leg-MUD in
      16 postnatally operated SBA children (MMC-L5; at 0, 6, and 12 months; in n =
      11/16; 11/16, and 15/16 children, respectively) and compared outcomes with 13
      healthy control children. Additionally, we assessed SBA MUD caudal and cranial to
      the MMC and calculated MMC-L5 impact by: dMUD((MMC-L5)) = [MUD(calf muscle/S1-2)]
      - [MUD(quadriceps muscle/L2-4)] and associated outcomes with leg muscle function
      caudal to the MMC. RESULTS: At 0 month, clinically discernible dMUD was more
      often increased in SBA than in control newborns (p < .05), but a relationship
      between absolute quantitative differences and leg muscle dysfunction was still
      lacking. At 6-12 months, additionally increased dMUD outcomes coincided with SBA
      leg muscle dysfunction (p < .05). CONCLUSIONS: In post-neonatal SBA, secondarily
      increased dMUD (i.e., MMC impact) coincides with leg muscle dysfunction. This may
      implicate that muscle ultrasound could provide a quantitative tool to assess the
      neuromuscular impact by the second hit of damage.

PMID- 23138436
TI  - Subependymal giant cell astrocytoma associated with tuberous sclerosis presenting
      with intratumoral bleeding. Case report and review of literature.
AB  - The authors describe a rare case of subependymal giant cell astrocytoma (SEGA)
      associated with tuberous sclerosis complex that presented with intratumoral
      bleeding with extension to the ventricles. The literature regarding intracranial
      hemorrhage of SEGA is reviewed and only five cases have been reported in the
      literature. We have not identified a histological feature associated with
      bleeding.

PMID- 23138437
TI  - Leading teams that thrive.
AB  - PURPOSE OF REVIEW: The purpose of this review is to explore pathways and develop
      specific knowledge and skills for leading teams that thrive. Here we will discuss
      current research findings and specific strategies you can use to create stronger
      more engaged work teams. RECENT FINDINGS: Recent research findings in leadership
      from the Gallup Organization and Vital Smarts provide the framework for this
      discussion. SUMMARY: When team members have clear expectations and role clarity,
      are engaged in conversations that matter, and have knowledge and skill to
      participate mindfully in crucial conversations, teams thrive.

PMID- 23138438
TI  - Metabolic correlates of menopause:  an update.
AB  - PURPOSE OF REVIEW: Metabolic syndrome (MetS) is a cluster of characteristics that
      increase the risk of cardiovascular disease and type 2 diabetes mellitus. We will
      review the most interesting and relevant studies on metabolic correlates of
      menopause published over the last year. RECENT FINDINGS: In the past year,
      studies have shifted focus from effects on cardiovascular disease and diabetes to
      effects of MetS on breast cancer as well as menopausal symptoms. Studies have
      found and further confirmed its negative effect on both breast cancer and
      menopausal symptoms. Focus has also been on treatment options including both
      lifestyle and pharmacologic. Recent studies also further investigate
      markers/predictors as well as genetic components influencing MetS development.
      SUMMARY: Over a quarter of the US population is affected by metabolic disease at
      midlife, and some studies have shown that the incidence of MetS increases with
      menopause. There are now more Americans who are age 65 and older than at any
      other time in US history. Thus, it is becoming ever more important to understand
      metabolic health, as well as the consequences of MetS.

PMID- 23138439
TI  - Updates in therapy for uterine serous carcinoma.
AB  - PURPOSE OF REVIEW: Uterine serous carcinoma (USC) is a highly aggressive variant
      of endometrial cancer with distinct molecular pathogenesis. This review
      summarizes the rationale behind current clinical approaches, as well as advances
      made in 2012 toward the elucidation of underlying pathway aberrations and
      development of targeted therapies that exploit these unique characteristics.
      RECENT FINDINGS: Within the last year, exome-wide analyses have highlighted key
      mutations to guide rational drug design. The PI3/AKT/mTOR pathway and regulators
      of cell cycle such as cyclin E/F-box proteins appear to be particularly
      important. Understanding the epithelial to mesenchymal transition may explain the
      aggressive pattern of spread frequently observed in this disease. There is
      heightened evidence for heritable syndromes in association with USC. Conflicting
      retrospective data continue to emerge regarding optimal therapy, especially for
      early-stage disease, although prospective studies are underway. Immunotherapies
      targeting Her2/Neu and vascular endothelial growth factor remain an area of
      active research. Upregulation of class III beta-tubulin observed in paclitaxel
      resistant disease may identify candidates for therapy with novel microtubule
      stabilizing agents such as epothilones. SUMMARY: There is an expanding role for
      contemporary novel approaches in the treatment of USC. The results of clinical
      investigations using new target antigens, epothilones, and small molecule
      inhibitors are eagerly awaited.

PMID- 23138440
TI  - Reducing door-to-needle times using Toyota's lean manufacturing principles and
      value stream analysis.
AB  - BACKGROUND AND PURPOSE: Earlier tissue-type plasminogen activator (tPA) treatment
      for acute ischemic stroke increases efficacy, prompting national efforts to
      reduce door-to-needle times. We used lean process improvement methodology to
      develop a streamlined intravenous tPA protocol. METHODS: In early 2011, a
      multidisciplinary team analyzed the steps required to treat patients with acute
      ischemic stroke with intravenous tPA using value stream analysis (VSA). We
      directly compared the tPA-treated patients in the "pre-VSA" epoch with the "post
      VSA" epoch with regard to baseline characteristics, protocol metrics, and
      clinical outcomes. RESULTS: The VSA revealed several tPA protocol inefficiencies:
      routing of patients to room, then to CT, then back to the room; serial processing
      of workflow; and delays in waiting for laboratory results. On March 1, 2011, a
      new protocol incorporated changes to minimize delays: routing patients directly
      to head CT before the patient room, using parallel process workflow, and
      implementing point-of-care laboratories. In the pre and post-VSA epochs, 132 and
      87 patients were treated with intravenous tPA, respectively. Compared with pre
      VSA, door-to-needle times and percent of patients treated <=60 minutes from
      hospital arrival were improved in the post-VSA epoch: 60 minutes versus 39
      minutes (P<0.0001) and 52% versus 78% (P<0.0001), respectively, with no change in
      symptomatic hemorrhage rate. CONCLUSIONS: Lean process improvement methodology
      can expedite time-dependent stroke care without compromising safety.

PMID- 23138442
TI  - Poststroke pharmacotherapy: another ictus.

PMID- 23138441
TI  - Early change in ferumoxytol-enhanced magnetic resonance imaging signal suggests
      unstable human cerebral aneurysm: a pilot study.
AB  - BACKGROUND AND PURPOSE: The clinical significance of early (ie, within the first
      24 hours) uptake of ferumoxytol by macrophages in the wall of human cerebral
      aneurysms is not clear. The purpose of this study was to determine whether early
      uptake of ferumoxytol suggests unstable cerebral aneurysm. METHODS: Thirty
      unruptured aneurysms in 22 patients were imaged with magnetic resonance imaging
      24 hours after infusion of ferumoxytol. Eighteen aneurysms were also imaged 72
      hours after infusion of ferumoxytol. Aneurysm dome tissue was collected from 4
      patients with early magnetic resonance imaging signal changes, 5 patients with
      late signal changes, and 5 other patients with ruptured aneurysms. The tissue was
      immunostained for expression of cyclooxygenase-1, cyclooxygenase-2, microsomal
      prostaglandin E2 synthase-1, and macrophages. RESULTS: In 23% (7/30) of
      aneurysms, there was pronounced early uptake of ferumoxytol. Four aneurysms were
      clipped. The remaining 3 aneurysms were managed conservatively; all 3 ruptured
      within 6 months. In 53% (16 of 30) of aneurysms, there was pronounced uptake of
      ferumoxytol at 72 hours. Eight aneurysms were surgically clipped, and 8 were
      managed conservatively; none ruptured or increased in size after 6 months.
      Expression of cyclooxygenase-2, microsomal prostaglandin E2 synthase-1, and
      macrophages was similar in unruptured aneurysms with early uptake of ferumoxytol
      and ruptured aneurysms. Expression of these inflammatory molecules was
      significantly higher in aneurysms with early uptake of ferumoxytol versus
      aneurysms with late uptake. CONCLUSIONS: Uptake of ferumoxytol in aneurysm walls
      within the first 24 hours strongly suggests aneurysm instability and probability
      of rupture within 6 months, and may warrant urgent intervention.

PMID- 23138443
TI  - Telephone assessment of cognition after transient ischemic attack and stroke:
      modified telephone interview of cognitive status and telephone Montreal Cognitive
      Assessment versus face-to-face Montreal Cognitive Assessment and
      neuropsychological battery.
AB  - BACKGROUND AND PURPOSE: Face-to-face cognitive testing is not always possible in
      large studies. Therefore, we assessed the telephone Montreal Cognitive Assessment
      (T-MoCA: MoCA items not requiring pencil and paper or visual stimulus) and the
      modified Telephone Interview of Cognitive Status (TICSm) against face-to-face
      cognitive tests in patients with transient ischemic attack (TIA) or stroke.
      METHODS: In a population-based study, consecutive community-dwelling patients
      underwent the MoCA and neuropsychological battery >1 year after TIA or stroke,
      followed by T-MoCA (22 points) and TICSm (39 points) at least 1 month later. Mild
      cognitive impairment (MCI) was diagnosed using modified Petersen criteria and the
      area under the receiver-operating characteristic curve (AUC) determined for T
      MoCA and TICSm. RESULTS: Ninety-one nondemented subjects completed
      neuropsychological testing (mean+/-SD age, 72.9+/-11.6 years; 54 males; stroke
      49%) and 73 had telephone follow-up. MoCA subtest scores for repetition,
      abstraction, and verbal fluency were significantly worse (P<0.02) by telephone
      than during face-to-face testing. Reliability of diagnosis for MCI (AUC) were T
      MoCA of 0.75 (95% confidence interval [CI], 0.63-0.87) and TICSm of 0.79 (95% CI,
      0.68-0.90) vs face-to-face MoCA of 0.85 (95% CI, 0.76-0.94). Optimal cutoffs were
      18 to 19 for T-MoCA and 24 to 25 for TICSm. Reliability of diagnosis for MCI
      (AUC) was greater when only multi-domain impairment was considered (T-MoCA=0.85;
      95% CI, 0.75-0.96 and TICSm=0.83, 95% CI, 0.70-0.96) vs face-to-face MoCA=0.87;
      95% CI, 0.76-0.97). CONCLUSIONS: Both T-MoCA and TICSm are feasible and valid
      telephone tests of cognition after TIA and stroke but perform better in detecting
      multi-domain vs single-domain impairment. However, T-MoCA is limited in its
      ability to assess visuoexecutive and complex language tasks compared with face-to
      face MoCA.

PMID- 23138444
TI  - Comparison of spontaneous intracerebral hemorrhage treatment in Germany between
      1999 and 2009: results of a survey.
AB  - BACKGROUND AND PURPOSE: The aim of our study was to examine surgical practice in
      the therapy of spontaneous intracerebral hemorrhage in Germany over a period of
      10 years. METHODS: In 1999 and 2009 a questionnaire with 10 different cases of
      spontaneous intracerebral hemorrhage was sent to all neurosurgical centers in
      Germany. It included a cranial CT as well as a case description. The question
      asked if a conservative or surgical procedure was most suitable. When choosing
      surgery, the participants could decide between large open approach or
      microsurgery as well as stereotactic aspiration or external ventricular drainage.
      RESULTS: In 1999, 85 of 121 (70%) and in 2009 111 of 125 (89%) questionnaires
      could be evaluated. The results of the questionnaires from 1999 and 2009 showed
      no difference in the decision for or against a surgical procedure, except for a
      move toward conservative treatment in 1 patient with a massive spontaneous
      intracerebral hemorrhage. In 2 cases of isolated basal ganglia bleeding, a
      conservative approach was chosen by approximately 98% of the participants both in
      1999 and in 2009. In all other cases of spontaneous intracerebral hemorrhage, in
      particular when the patient was in poor clinical condition, the decision was very
      heterogeneous. CONCLUSIONS: Despite new studies, there were no significant
      differences regarding the decision for or against a surgical procedure in 1999
      and 2009. Although clearly unfavorable prognostic factors are known, many
      patients still undergo a surgical procedure. It appears that at least spontaneous
      intracerebral hemorrhage in the area of the basal ganglia is a unique domain of
      conservative treatment.

PMID- 23138445
TI  - Encapsulation of clay by ad-miniemulsion polymerization: the influence of clay
      size and modifier reactivity on latex morphology and physical properties.
AB  - The influence of clay platelet size and type of organic modifier (reactive or
      nonreactive) on highly filled hybrid latex morphology and physical properties of
      the resultant polymer/clay nanocomposites (PCNs) were investigated. The hybrid
      latexes, containing clay loadings between 30 and 50 wt % clay, were prepared
      using ad-miniemulsion polymerization. These materials have potential use in the
      packaging and coating industry since clay platelets are well-known for barrier
      property improvements. Comparative studies on the use of montmorillonite (MMT), a
      large clay platelet (average size: 50-500 nm), and Laponite (Lap), small-sized
      clay platelets (average size: 25-40 nm), were conducted. Two different clay
      modifiers were used to modify the clays, i.e., a conventional nonreactive
      modifier (cetyltrimethylammonium bromide (CTAB)) and a reactive modifier
      (vinylbenzyldodecyldimethylammonium chloride (VBDAC)). Transmission electron
      microscopy (TEM) imaging of the hybrid latexes clearly showed strong
      morphological dependency on both the type of modifier and the clay platelet size.
      Furthermore, TEM together with small-angle X-ray scattering (SAXS) showed that
      the extent of clay exfoliation was strongly dependent on the reactivity of the
      clay modifier, irrespective of the clay platelet size. Both the type of modifier
      and clay platelets size were found to have an influence on different physical
      properties of the resultant PCNs. The influence of clay size was clearly
      indicated by storage modulus and thermal stability behaviors, while that of the
      clay modifier was indicated by the T(g). Lap-based PCNs exhibited constant or
      increasing storage modulus and no change in thermal stability with increasing
      clay content, while MMT-based PCNs showed a decreasing trend in both storage
      modulus and thermal stability. PCNs based on clay modified with CTAB showed a
      decreasing T(g) with increasing clay content, while those based on clay modified
      with VBDAC showed an increasing trend. It was concluded that the clay platelet
      size and the type of modifier play a crucial part of both the latex morphology
      and the physical properties of the resultant PCNs.

PMID- 23138446
TI  - Formation of surface relief grating in polymers with pendant azobenzene
      chromophores as studied by AFM/UFM.
AB  - We studied peculiarities of the structural reconstruction within holographically
      recorded gratings on the surface of several different amorphous azobenzene
      containing polymers. Under illumination with a light interference pattern, two
      processes take place in this type of polymer. The first process is the light
      induced orientation of azobenzene units perpendicular to the polarization plane
      of the incident light. The second one is a transfer of macromolecules along the
      grating vector (i.e. perpendicular to the grating lines). These two processes
      result in the creation of a volume orientation grating (alternating regions of
      different direction or degree of molecular orientation) and a surface relief
      grating (SRG)-i.e. modulation of film thickness. One can assume that both
      orientation of molecules and their movement might change the local mechanical
      properties of the material. Therefore, formation of the SRG is expected to result
      also in modulation of the local stiffness of the polymer film. To reveal and
      investigate these stiffness changes within the grating, spin-coated polymer films
      were prepared and the gratings were recorded on them in two different ways: with
      an orthogonal circular or orthogonal linear polarization of two recording light
      beams. A combination of atomic force microscopy (AFM) and ultrasonic force
      microscopy (UFM) techniques was applied for SRG development monitoring. We
      demonstrate that formation of the phase gratings depends on the chemical
      structure of polymers being used, polymer film thickness, and recording
      parameters, with the height of grating structures (depth of modulation)
      increasing with both the exposure time and the film thickness. UFM images suggest
      that the slopes of the topographic peaks in the phase gratings exhibit an
      increased stiffness with respect to the grating depressions.

PMID- 23138447
TI  - Evaluation of the efficacy and safety of etanercept 50 mg once weekly in Japanese
      patients with rheumatoid arthritis and comparison with 25 mg etanercept twice
      weekly.
AB  - OBJECTIVE: Tumor necrosis factor-alpha inhibitors have been available in recent
      years for treating early and established rheumatoid arthritis (RA). Twice-weekly
      administration of 25 mg etanercept (ETN) has demonstrated efficacy and safety.
      The objective of this study was to evaluate the efficacy of once-weekly
      administration of 50 mg ETN (ETN50), and to compare it with that of twice-weekly
      administration of 25 mg ETN (ETN25). METHODS: The ETN50 group comprised 29
      patients and the ETN25 group 26. The analysis compared changes from baseline in
      Disease Activity Score in 28 joints (DAS28)-C reactive protein (CRP) and DAS28
      erythrocyte sedimentation rate (ESR) between the ETN50 and ETN25 groups. RESULTS:
      Overall, 42.3 % of ETN50 patients achieved DAS28-ESR remission (<2.6), and 76.9 %
      experienced low disease activity at 24 weeks. Patients in the ETN50 group also
      experienced more significant improvement in DAS28-ESR at 4 weeks, higher DAS28
      ESR remission rates, and lower disease activity rates than ETN25 group patients.
      No serious adverse events were experienced in the safety analysis set (ETN50
      group). CONCLUSION: These results suggest that ETN50 can lead to earlier
      remission and higher remission rates compared with ETN25 in patients with RA.

PMID- 23138448
TI  - Effect of platinum loading on fuel cell cathode performance using hydrocarbon
      ionomers as binders.
AB  - The effect of platinum loading on cathode performance in hydrogen/oxygen fuel
      cells was investigated using perfluorosulfonic acid (Nafion), sulfonated
      polyimide (SPI-8) and sulfonated poly(phenylene ether ether ketone) (SPEEK)
      ionomers as the electrode binder. By lowering the platinum loading, the cathode
      polarization decreased for MEAs using SPI-8 and SPEEK binders at high humidity
      (90-100% RH (relative humidity)) due to an improvement of mass transport (oxygen
      supply and/or water discharge) in the catalyst layer. In contrast, at humidity
      lower than 80% RH, the effect of platinum loading on the cathode performance
      differed between these two hydrocarbon (HC) ionomers. When SPI-8 was used as the
      binder, the cathode polarization increased when lowering the platinum loading due
      to an increase of activation overpotential. When SPEEK was used as the binder,
      the effect of platinum loading on the cathode performance was smaller. Such
      differences can be ascribed to the specific adsorbability of these hydrocarbon
      binders on the platinum catalyst at low humidity. These results point to crucial
      factors in achieving higher performance at low platinum loadings and low humidity
      using HC binders.

PMID- 23138449
TI  - Efficacy and safety of taspoglutide versus sitagliptin for type 2 diabetes
      mellitus (T-emerge 4 trial).
AB  - INTRODUCTION: The efficacy and safety of taspoglutide, a long-acting human
      glucagon-like peptide-1 analog, were compared with sitagliptin or placebo, as
      adjunct to metformin, in patients with inadequately controlled type 2 diabetes.
      METHODS: In this randomized, double-blind, double-dummy, parallel-group trial,
      patients were randomized to taspoglutide 10 mg once weekly (QW), 20 mg QW, 100 mg
      sitagliptin once daily (QD), or placebo for 24 weeks, followed by 28-week short
      term and 104-week long-term extension periods. The primary endpoint was change in
      glycosylated hemoglobin (HbA(1c)) after 24 weeks. RESULTS: In this study, 666
      patients (baseline HbA(1c), 7.96% [SD, 0.87]; fasting plasma glucose, 9.61 mmol/L
      [2.56]; body weight, 92.4 kg [19.3]) were randomized to taspoglutide 10 mg QW (n
      = 190), 20 mg QW (n = 198), 100 mg sitagliptin QD (n = 185), or placebo (n = 93)
      for 24 weeks. After 24 weeks, least squares mean (SE) HbA(1c) reductions were
      greater with taspoglutide 10 mg (-1.23% [0.06]) and 20 mg (-1.30% [0.06]) versus
      sitagliptin (-0.89% [0.06]) or placebo (-0.10% [0.08]). Mean treatment
      differences with taspoglutide 10 mg and 20 mg were -0.34 (95% confidence
      intervals [CI]: -0.49, -0.19) and -0.41 (-0.56, -0.26) versus sitagliptin; and 
      1.13 (-1.31, -0.95) and -1.20 (-1.38, -1.02) versus placebo. Weight loss was
      greater with taspoglutide 10 mg (-1.8 kg [0.3]) and 20 mg (-2.6 kg [0.3]) than
      sitagliptin (-0.9 kg [0.3]) or placebo (-0.5 kg [0.4]). Effects on HbA(1c) and
      weight loss continued through 52 weeks of treatment. No cases of severe
      hypoglycemia occurred with any active treatment. Gastrointestinal adverse events,
      and allergic and injection-site reactions were higher in the taspoglutide groups,
      causing higher discontinuation rates. Anti-taspoglutide antibodies were confirmed
      in 46% of patients. CONCLUSION: Taspoglutide demonstrated better efficacy on
      glycemic control and weight loss than sitagliptin, but a high incidence of
      adverse events led to high discontinuation rates. The safety profile of
      taspoglutide in this trial was similar to other trials in the clinical program,
      and led to the discontinuation of dosing.

PMID- 23138450
TI  - Accident at the Fukushima Dai-ichi nuclear power stations of TEPCO--outline &
      lessons learned.
AB  - The severe accident that broke out at Fukushima Dai-ichi nuclear power stations
      on March 11, 2011, caused seemingly infinite damage to the daily life of
      residents. Serious and wide-spread contamination of the environment occurred due
      to radioactive materials discharged from nuclear power stations (NPSs). At the
      same time, many issues were highlighted concerning countermeasures to severe
      nuclear accidents. The accident is outlined, and lessons learned are extracted
      with respect to the safety of NPSs, as well as radiation protection of residents
      under the emergency involving the accident. The materials of the current paper
      are those released by governmental agencies, academic societies, interim reports
      of committees under the government, and others.

PMID- 23138452
TI  - A group of glycosphingolipids found in an invertebrate: their structures and
      biological significance.
AB  - A novel group of glycosphingolipids was identified in the nervous tissue and skin
      of the mollusc, Aplysia kurodai, which lacks gangliosides. More than 30
      glycolipids were detected on HPTLC plates and the structures of 9 major
      glycolipids were determined. They were pentaosylglycosphingolipids and their
      common core structure was GalNAcalpha1->3Galbeta1->4Glcbeta1->1ceramide, except
      for one glycolipid in which Galbeta of the core structure was replaced by
      Galalpha. 3-O-MeGalbeta or 4-O-MeGlcNAcalpha or 3,4-O-carboxyethylideneGalbeta
      was at their non-reducing ends. Galalpha or Fucalpha binds to Gal of the core
      structure at 2C as a side chain sugar. One to three 2-aminoethylphosphonic acids
      and/or phosphoethanolamine link to the glycolipids. Immunohistochemically,
      glycolipids having carboxyethylideneGal at their non-reducing ends were localized
      exclusively in nerve bundles. Glycolipids activated cAMP-dependent protein kinase
      in the rat brain and may directly activate cAMP-dependent protein kinase in a
      manner similar, but not identical, to that of cAMP. The biological functions of
      glycolipids may share neurobiological functions proposed for gangliosides in
      vertebrates.

PMID- 23138453
TI  - The native cell population does not contribute to central-third graft healing at
      6, 12, or 26 weeks in the rabbit patellar tendon.
AB  - Investigators do not yet understand the role of intrinsic tendon cells in healing
      at the tendon-to-bone enthesis. Therefore, our first objective was to understand
      how the native cell population influences tendon autograft incorporation in the
      central-third patellar tendon (PT) defect site. To do this, we contrasted the
      histochemical and biomechanical properties of de-cellularized patellar tendon
      autograft (dcPTA) and patellar tendon autograft (PTA) repairs in the skeletally
      mature New Zealand white rabbit. Recognizing that soft tissues in many animal
      models require up to 26 weeks to incorporate into bone, our second objective was
      to investigate how recovery time affects enthesis formation and graft tissue
      biomechanical properties. Thus, we examined graft structure and mechanics at 6,
      12, and 26 weeks post-surgery. Our results showed that maintaining the native
      cell population produced no histochemical or biomechanical benefit at 6, 12, or
      26 weeks. These findings suggest that PTA healing is mediated more by extrinsic
      rather than intrinsic cellular mechanisms. Moreover, while repair tissue
      biomechanical properties generally increased from 6 to 12 weeks after surgery, no
      further improvements were noted up to 26 weeks.

PMID- 23138451
TI  - Prokaryotic genome regulation: a revolutionary paradigm.
AB  - After determination of the whole genome sequence, the research frontier of
      bacterial molecular genetics has shifted to reveal the genome regulation under
      stressful conditions in nature. The gene selectivity of RNA polymerase is
      modulated after interaction with two groups of regulatory proteins, 7 sigma
      factors and 300 transcription factors. For identification of regulation targets
      of transcription factors in Escherichia coli, we have developed Genomic SELEX
      system and subjected to screening the binding sites of these factors on the
      genome. The number of regulation targets by a single transcription factor was
      more than those hitherto recognized, ranging up to hundreds of promoters. The
      number of transcription factors involved in regulation of a single promoter also
      increased to as many as 30 regulators. The multi-target transcription factors and
      the multi-factor promoters were assembled into complex networks of transcription
      regulation. The most complex network was identified in the regulation cascades of
      transcription of two master regulators for planktonic growth and biofilm
      formation.

PMID- 23138454
TI  - Influence of dentin and enamel pretreatment with acidic sulfur compounds on
      adhesive performance.
AB  - OBJECTIVE: This study tested the potential hampering effects of acidic sulfur
      compounds (ASC) containing hydroxybenzene sulfonic acid, hydroxymethoxybenzene
      sulfonic acid, and sulfuric acid, prior to self-etch and etch-and-rinse bonding
      procedures on enamel and dentin. According to the manufacturer, ASC should be
      applied after cavity preparation and prior to application of a primer in order to
      reduce the remaining biofilm in the preparation cavity. Despite promoted
      marketing, data on the investigated liquid are almost completely lacking.
      MATERIAL AND METHODS: One hundred and fifty-two extracted mandibular bovine
      incisors were embedded and polished to expose either enamel (E) or dentin (D).
      Then, specimens were randomly divided and conditioned as follows (n = 12/group):
      ASC and consecutive phosphoric acid application (E1/D1), ASC (E2/D2; E5/D5),
      phosphoric acid (E3/D3), and no conditioning (E4/D4; E6/D6). Groups were then
      treated with either Optibond FL((r)) (etch-and-rinse; 1-4) or Clearfil SE
      Bond((r)) (self-etch; 5-6). Hollow acrylic cylinders were bonded with a hybrid
      composite resin (Filtek Supreme XTE(r)) to the specimens, and the shear bond
      strength was measured (1 mm/min). In addition, failure types were assessed.
      Descriptive statistics and statistical analyses were performed with one-way ANOVA
      followed by the Scheffe post hoc test. RESULTS: For enamel, the highest shear
      bond strength values were obtained applying routine bonding procedures (23.5 +/-
      5.6 MPa for etch-and-rinse and 26.0 +/- 6.0 MPa for self-etch, respectively). In
      contrast, dentin pretreatment with a combination of ASC and phosphoric acid led
      to the highest shear bond values (22.8 +/- 4.1 MPa). CONCLUSION: This study shows
      that ASC prior to dental restoration placement cannot be recommended for etch-and
      rinse procedures on enamel but is appropriate for dentin without interfering with
      routine bonding procedures. CLINICAL RELEVANCE: The application of acidic sulfur
      compounds prior to adhesive restoration placement should be restricted to dentin
      only as it may negatively influence shear bond strength on sound enamel.

PMID- 23138455
TI  - Induction of immunological memory response by vaccination with TM4SF5 epitope-CpG
      DNA-liposome complex in a mouse hepatocellular carcinoma model.
AB  - The innovation of a peptide vaccine strategy may contribute to the development of
      efficacious and convenient cancer vaccines. Recently, we formulated an
      efficacious peptide vaccine without carriers using the natural phosphodiester
      bond CpG-DNA and a special liposome complex [Lipoplex(O)]. The peptide vaccine
      targeting a tumor antigen, transmembrane 4 superfamily member 5 protein (TM4SF5),
      was confirmed to have preventive and therapeutic effects in a mouse
      hepatocellular carcinoma (HCC) model. In this study, we demonstrated that the
      isotype-switched (IgM(-)IgD(-)) B cell population increased after immunization
      and that the functional memory response persisted for at least 70 days after the
      final immunization of mice. Delayed implantation of BNL-HCC cells significantly
      induced the peptide-specific IgG2a production in the immunized mice. Accordingly,
      tumor growth was inhibited and the survival rate increased. These results suggest
      that our peptide vaccine induces memory response, which is essential for cancer
      vaccine application.

PMID- 23138456
TI  - Asymmetric skull deformity in children with cerebral palsy: frequency and
      correlation with postural abnormalities and deformities.
AB  - OBJECTIVE: Asymmetrical skull deformity is frequently seen in children with
      cerebral palsy, and may contribute to postural abnormalities and deformities. The
      aim of this cross-sectional- survey was to determine the frequency of
      asymmetrical skull deformity and its correlation with clinical parameters.
      METHODS: A 10-item checklist for asymmetrical skull deformity, postural
      abnormalities, and deformities was developed, and its inter-rater reliability was
      tested. A total of 110 participants aged 1-18 years (mean age 9.3 years (standard
      deviation 4.7)) was assessed using the checklist. The frequency of asymmetrical
      skull deformity was analysed and related to the Gross Motor Function
      Classification System (GMFCS), postural abnormalities, and deformities. RESULTS:
      The reliability of the checklist was satisfactory (kappa > 0.8). Asymmetrical
      skull deformity was observed in 44 children, 24 showing right and 20 showing left
      flat occipital deformity. Its frequency was significantly related to GMFCS and
      with the patterns of asymmetrical posture and deformities (p < 0.05). Children
      with right flat occipital asymmetrical skull deformity showed predominantly
      rightward facial direction and right-side-dominant asymmetrical tonic neck
      reflex, left convex scoliosis, right-side-elevated pelvic obliquity, and left
      sided hip dislocation. Those with left flat occipital asymmetrical skull
      deformity demonstrated the reverse tendency. CONCLUSION: Asymmetrical skull
      deformity is frequent in cerebral palsy and closely related to asymmetrical
      posture and deformities. This information will be useful to manage these
      problems.

PMID- 23138457
TI  - Molecular characterization and expression analysis of GlHMGS, a gene encoding
      hydroxymethylglutaryl-CoA synthase from Ganoderma lucidum (Ling-zhi) in ganoderic
      acid biosynthesis pathway.
AB  - A hydroxymethylglutaryl-CoA synthase gene, designated as GlHMGS (GenBank
      accession No. JN391469) involved in ganoderic acid (GA) biosynthesis pathway was
      cloned from Ganoderma lucidum. The full-length cDNA of GlHMGS (GenBank accession
      No. JN391468) was found to contain an open reading frame of 1,413 bp encoding a
      polypeptide of 471 amino acid residues. The deduced amino acid sequence of GlHMGS
      shared high homology with other known hydroxymethylglutaryl-CoA synthase (HMGS)
      enzymes. In addition, functional complementation of GlHMGS in a mutant yeast
      strain YSC1021 lacking HMGS activity demonstrated that the cloned cDNA encodes a
      functional HMGS. A 1,561 bp promoter sequence was isolated and its putative
      regulatory elements and potential specific transcription factor binding sites
      were analyzed. GlHMGS expression profile analysis revealed that salicylic acid,
      abscisic acid and methyl jasmonate up-regulated GlHMGS transcript levels over the
      control. Further expression analysis revealed that the developmental stage and
      carbon source had significant effects on GlHMGS transcript levels. GlHMGS
      expression peaked on day 16 before decreasing with prolonged culture time. The
      highest mRNA level was observed when the carbon source was maltose.
      Overexpression of GlHMGS enhanced GA content in G. lucidum. This study provides
      useful information for further studying this gene and on its function in the
      ganoderic acid biosynthetic pathway in G. lucidum.

PMID- 23138458
TI  - Two-photon excited fluorescence of silica nanoparticles loaded with a fluorene
      based monomer and its cross-conjugated polymer: their application to cell
      imaging.
AB  - In this work the two-photon activity of nanoparticles obtained from a fluorene
      monomer (M1) and its cross-conjugated polymer (P1) is reported. Aqueous
      suspensions of M1 and P1 nanoparticles prepared through the reprecipitation
      method exhibited maximum two-photon absorption (TPA) cross-sections of 84 and
      9860 GM (1 GM = 10(-50) cm(4) s) at 740 nm, respectively, and a fluorescence
      quantum yield of ~1. Such a two-photon activity was practically equal with
      respect to that for molecular solutions of M1 and P1. These materials were then
      successfully encapsulated into silica nanoparticles to provide bio-compatibly. A
      lung cancer cell line (A549) and a human cervical cancer cell line (HeLa cells)
      were incubated with our fluorescent silica nanoparticles to carry out two-photon
      imaging. By means of these studies we demonstrate that optimized nonlinear
      optical polymers loaded in silica nanoparticles can be used as efficient probes
      with low cytotoxicity and good photostability for two-photon fluorescence
      microscopy. To the best of our knowledge, studies concerning polymer-doped silica
      nanoparticles exhibiting large two-photon activity have not been reported in the
      literature.

PMID- 23138459
TI  - Structural diversity directed by switchable coordination of substitute groups in
      a ternary Cu(II)-triazole-sulfoisophthalate self-assembly system: synthesis,
      crystal structures and magnetic behavior.
AB  - Four magnetic samples with different building blocks and dimensionalities,
      {[Cu(4)(atr)(2)(MU(3)-OH)(2)(sip)(2)].4H(2)O}(n) (1),
      {[Cu(4)(atr)(2)(H(2)O)(8)(MU-OH)(2)(sip)(2)].1.3CH(3)OH.0.7H(2)O}(n) (2),
      {[Cu(3)(atr)(4)(H(2)O)(2)(sip)(2)].4H(2)O}(n) (3) and
      {[Cu(3)(atr)(4)(H(2)O)(2)(MU(3)-OH)(sip)(Hsip)].2CH(3)OH.2.75H(2)O}(n) (4) (atr =
      4-amino-1,2,4-triazole and sip(3-) = 5-sulfoisophthalate), were obtained and
      characterized structurally and magnetically. Complex 1 exhibits a three
      dimensional (3D) robust framework with butterfly-like Cu(II)(4) clusters
      periodically extended by tetratopic sip(3-) connectors. Complex 2 possesses a 2D
      layer with alternating Cu(II)(3) + Cu(II)(1) chains crosslinked by pairs of
      ditopic sip(3-) linkers. By contrast, the latter two entities feature 1D broad
      ribbons with linear (for 3) and triangular Cu(II)(3) cores (for 4) propagated by
      bidirectional sip(3-) connectors. Structural analysis reveals that the diverse
      building blocks and dimensionalities of 1-4 are significantly dominated by the
      tunable coordination of exocyclic amino- and/or sulfonate-group of the mixed
      ligands. Magnetically, antiferromagnetic interactions with variable strength
      transmitted by -NN- moiety of atr and hydroxyl mediators result in overall S = 0
      (for 1) and 1/2 (for 3 and 4) spin ground states. These interesting results
      indicate that coordinative side group in the ternary metal ion-azolate
      carboxylate system can be utilized to generate aesthetically pleasing building
      units and variably polytopic connectors, leading to differently extended
      superstructures and magnetic behavior.

PMID- 23138460
TI  - Circulating and platelet-derived microparticles in human blood enhance thrombosis
      on atherosclerotic plaques.
AB  - Plaque rupture followed by thrombosis is the underlying cause of the majority of
      acute coronary syndromes. Circulating microparticles (cMPs), membrane blebs
      released into blood by activated cells, have been associated to vascular
      diseases. Specifically, high levels of platelet-derived microparticles (pMPs)
      have been found in patients with coronary disease. However, it is unknown whether
      microparticles have a contributing role to the development of damaged vessel wall
      induced arterial thrombi. The aim of this proof of concept study was to
      investigate whether an increased number of cMPs and pMPs could functionally
      contribute to blood thrombogenicity on areas of arterial damage. Microparticles
      were isolated from blood of healthy volunteers and were characterised by flow
      cytometry. Effects of microparticles on platelet deposition were assessed under
      controlled flow conditions exposing damaged arterial wall in the Badimon
      perfusion chamber and collagen type-I in the flat perfusion chamber to human
      blood. Platelet deposition on damaged arteries was significantly increased in cMP
      and pMP-enriched bloods (p<0.05). pMPs also induced increase in platelet
      (p<0.05) and fibrin (p<0.05) deposition on human atherosclerotic arteries and in
      platelet adhesion to purified collagen surfaces. pMP-enriched blood induced a
      dose-dependent shortening of epinephrine/collagen closure time evaluated by PFA
      100 (p<0.001), increased low-dose ADP-induced platelet aggregation by LTA
      (p<0.05), and decreased clotting time by thromboelastography (p<0.01). In
      conclusion, an increased content of cMPs and pMPs, even in normal blood
      conditions, enhance platelet deposition and thrombus formation. This study shows
      for the first time that, beyond biomarkers of cell activation, blood
      microparticles have functional effects on cardiovascular atherothrombotic
      disease.

PMID- 23138461
TI  - Physicians in leadership: the association between medical director involvement
      and staff-to-patient ratios.
AB  - In a hospital environment that demands a careful balance between commercial and
      clinical interests, the extent to which physicians are involved in hospital
      leadership varies greatly. This paper assesses the influence of the extent of
      this involvement on staff-to-patient ratios. Using data gathered from 604
      hospitals across Germany, this study evidences the positive relationship between
      a full-time medical director (MD) or heavily involved part-time MD and a higher
      staff-to-patient ratio. The data allows us to control for a range of confounding
      variables, such as size, rural/urban location, ownership structure, and case-mix.
      The results contribute to the sparse body of empirical research on the effect of
      clinical leadership on organizational outcomes.

PMID- 23138462
TI  - Human amniotic fluid derived cells can competently substitute dermal fibroblasts
      in a tissue-engineered dermo-epidermal skin analog.
AB  - PURPOSE: Human amniotic fluid comprises cells with high differentiation capacity,
      thus representing a potential cell source for skin tissue engineering. In this
      experimental study, we investigated the ability of human amniotic fluid derived
      cells to substitute dermal fibroblasts and support epidermis formation and
      stratification in a humanized animal model. METHODS: Dermo-epidermal skin grafts
      with either amniocytes or with fibroblasts in the dermis were compared in a rat
      model. Full-thickness skin wounds on the back of immuno-incompetent rats were
      covered with skin grafts with (1) amniocytes in the dermis, (2) fibroblasts in
      the dermis, or, (3) acellular dermis. Grafts were excised 7 and 21 days post
      transplantation. Histology and immunofluorescence were performed to investigate
      epidermis formation, stratification, and expression of established skin markers.
      RESULTS: The epidermis of skin grafts engineered with amniocytes showed near
      normal anatomy, a continuous basal lamina, and a stratum corneum. Expression
      patterns for keratin 15, keratin 16, and Ki67 were similar to grafts with
      fibroblasts; keratin 1 expression was not yet fully established in all suprabasal
      cell layers, expression of keratin 19 was increased and not only restricted to
      the basal cell layer as seen in grafts with fibroblasts. In grafts with acellular
      dermis, keratinocytes did not survive. CONCLUSION: Dermo-epidermal skin grafts
      with amniocytes show near-normal physiological behavior suggesting that
      amniocytes substitute fibroblast function to support the essential cross-talk
      between mesenchyme and epithelia needed for epidermal stratification. This novel
      finding has considerable implications regarding tissue engineering.

PMID- 23138463
TI  - Association of Hashimoto's thyroiditis with cytotoxic T lymphocyte-associated
      antigen-4 (CTLA-4) and inducible co-stimulator (ICOS) genes in a Kuwaiti
      population.
AB  - Analysing two CTLA-4 markers [exon 1 A49G single nucleotide polymorphism (SNP)
      and exon 4 3'UTR (AT)n repeat] and the ICOS intron 4 (GT)n marker for their
      potential association with HT, and exploring the effect of the tested SNPs on the
      CTLA-4 isoform expression at the mRNA and protein levels. Total of 270 age-gender
      ethnically matched subjects were genotyped by fluorescent-labelled restriction
      fragment length polymorphism, multiplex PCR, and fragment analysis. Sequencing
      was used to confirm the genotyping results. Expression of the full-length and
      soluble CTLA-4 mRNAs analysed using real-time PCR. Sera from subjects were
      screened for sCTLA-4 using ELISA. Tested subjects revealed ten alleles and
      sixteen genotypes of CTLA-4 3'UTR(AT)n. The 3'UTR(AT)n was significantly
      associated with HT: allele (AT)15 and genotype 15/15 were found to cause
      susceptibility to HT (P = 0.004, OR = 2.13, 95 % CI = 1.26-3.58 and P = 0.029, OR
      = 2.77, 95 % CI = 1.1-6.94, respectively), whereas allele (AT)6 and genotype 6/6
      were found to be protective of HT (P = 0.00002, OR = 0.36, 95 % CI = 0.227-0.57
      and P = 0.001, OR = 0.357, 95 % CI = 0.1980.64, respectively). SNP A49G and
      ICOS(GT)n revealed no significant association with HT (P > 0.05). The expression
      of sCTLA-4 was inversely proportional to the number of 3'UTR(AT)n repeats, with
      heterozygous and longer (AT)n repeats showing lower levels of sCTLA-4 mRNA than
      those with shorter alleles in HC and HT (P = 0.001 and P = 0.04, respectively).
      Significant increase in the serum level of sCTLA-4 was observed in HT patients
      compared with the HC (P = 0.0007). The novel finding in our study is that the
      CTLA-4 3'UTR(AT)n proven to be a key player in the pathogenesis of HT.

PMID- 23138464
TI  - TLR-10 polymorphism and papillary thyroid cancer: one more SNP to consider?

PMID- 23138466
TI  - New emerging technologies in benign prostatic hyperplasia.
AB  - PURPOSE OF REVIEW: Transurethral resection of the prostate has long been held as
      the gold standard for treatment of benign prostatic hyperplasia (BPH); however,
      there have been significant innovations in other less invasive alternative
      treatments for BPH in recent years. Our purpose is to present emerging surgical
      treatment modalities which have been presented in the last 12 months. RECENT
      FINDINGS: We report recent results in different treatment options for BPH. The
      concept of stenting the urethra has already been introduced nearly 20 years ago
      in urology and like intraprostatic injection of botulinum toxin it has found
      application in urological treatment of bladder outlet obstruction. The prostatic
      urethral lift procedure is a novel surgical minimal invasive approach needing
      long-term results. Intraprostatic injections with NX-1207 and histotripsy
      fractionation of prostate tissue are treatment modalities, which are currently
      under evaluation for a clinical application in humans. SUMMARY: Anaesthesia-free
      outpatient capability, lack of sexual side-effects and avoidance of actual
      surgery are attractive to patient and clinician alike. Some of the presented
      treatments may establish in clinical practice as a suitable treatment alternative
      to transurethral resection of the prostate and medical therapy.

PMID- 23138465
TI  - Chemopreventive and anti-angiogenic effects of dietary phenethyl isothiocyanate
      in an N-methyl nitrosourea-induced breast cancer animal model.
AB  - The effect of phenethyl isothiocyanate (PEITC), a component of cruciferous
      vegetables, on the initiation and progression of cancer was investigated in a
      chemically induced estrogen-dependent breast cancer model. Breast cancer was
      induced in female Sprague Dawley rats (8 weeks old) by the administration of N
      methyl nitrosourea (NMU). Animals were administered 50 or 150 umol/kg oral PEITC
      and monitored for tumor appearance for 18 weeks. The PEITC treatment prolonged
      the tumor-free survival time and decreased the tumor incidence and multiplicity.
      The time to the first palpable tumor was prolonged from 69 days in the control,
      to 84 and 88 days in the 50 and 150 umol/kg PEITC-treated groups. The tumor
      incidence in the control, 50 umol/kg, and 150 umol/kg PEITC-treated groups was
      56.6%, 25.0% and 17.2%, while the tumor multiplicity was 1.03, 0.25 and 0.21,
      respectively. Differences were statistically significant (p < 0.05) from the
      control, but there were no significant differences between the two dose levels.
      The intratumoral capillary density decreased from 4.21 +/- 0.30 vessels per field
      in the controls to 2.46 +/- 0.25 in the 50 umol/kg and 2.36 +/- 0.23 in the 150
      umol/kg PEITC-treated animals. These studies indicate that supplementation with
      PEITC prolongs the tumor-free survival, reduces tumor incidence and burden, and
      is chemoprotective in NMU-induced estrogen-dependent breast cancer in rats. For
      the first time, it is reported that PEITC has anti-angiogenic effects in a
      chemically induced breast cancer animal model, representing a potentially
      significant mechanism contributing to its chemopreventive activity.

PMID- 23138467
TI  - Imaging in benign prostatic hyperplasia:  what is new?
AB  - PURPOSE OF REVIEW: This article discusses the new imaging techniques in diagnosis
      and treatment of benign prostatic hyperplasia by reviewing the most recent
      publications. RECENT FINDINGS: Imaging study for the evaluation of patients with
      lower urinary tract symptoms is not suggested by American Urology Association
      guidelines; however, European Association of Urology recommends the assessment of
      the upper urinary tract by modalities like ultrasound. Several new imaging
      indices like resistive index of capsular artery, presumed circle area ratio,
      prostatic urethral angle, intraprostatic protrusion, and detrusor wall thickness
      are used to find a noninvasive way for bladder outlet obstruction diagnosis. In
      addition to them, 3D transrectal ultrasound, near infrared spectroscopy, and MRI
      are used to add more practical findings in patient management. SUMMARY:
      Urologists have requested more imaging studies than expected for benign prostatic
      hyperplasia patients in recent years, and several studies have been done to find
      a noninvasive way to diagnose bladder outlet obstruction. However, none of them
      could play the urodynamic studies role in bladder outlet obstruction diagnosis.

PMID- 23138468
TI  - MRI-ultrasound fusion for guidance of targeted prostate biopsy.
AB  - PURPOSE OF REVIEW: Prostate cancer (CaP) may be detected on MRI. Fusion of MRI
      with ultrasound allows urologists to progress from blind, systematic biopsies to
      biopsies, which are mapped, targeted and tracked. We herein review the current
      status of prostate biopsy via MRI/ultrasound fusion. RECENT FINDINGS: Three
      methods of fusing MRI for targeted biopsy have been recently described: MRI
      ultrasound fusion, MRI-MRI fusion ('in-bore' biopsy) and cognitive fusion.
      Supportive data are emerging for the fusion devices, two of which received US
      Food and Drug Administration approval in the past 5 years: Artemis (Eigen, USA)
      and Urostation (Koelis, France). Working with the Artemis device in more than 600
      individuals, we found that targeted biopsies are two to three times more
      sensitive for detection of CaP than nontargeted systematic biopsies; nearly 40%
      of men with Gleason score of at least 7 CaP are diagnosed only by targeted
      biopsy; nearly 100% of men with highly suspicious MRI lesions are diagnosed with
      CaP; ability to return to a prior biopsy site is highly accurate (within 1.2 +/-
      1.1 mm); and targeted and systematic biopsies are twice as accurate as systematic
      biopsies alone in predicting whole-organ disease. SUMMARY: In the future, MRI
      ultrasound fusion for lesion targeting is likely to result in fewer and more
      accurate prostate biopsies than the present use of systematic biopsies with
      ultrasound guidance alone.

PMID- 23138469
TI  - So you want to be a robotic surgeon?

PMID- 23138470
TI  - Letter to the editor regarding "Quantification of paraquat, MPTP, and MPP+ in
      brain tissue using microwave-assisted solvent extraction (MASE) and high
      performance liquid chromatography-mass spectrometry".

PMID- 23138471
TI  - MALDI imaging in human skin tissue sections: focus on various matrices and
      enzymes.
AB  - Matrix-assisted laser/desorption ionization (MALDI) mass-spectrometric imaging
      (MSI), also known as MALDI imaging, is a powerful technique for mapping
      biological molecules such as endogenous proteins and peptides in human skin
      tissue sections. A few groups have endeavored to apply MALDI-MSI to the field of
      skin research; however, a comprehensive article dealing with skin tissue sections
      and the application of various matrices and enzymes is not available. Our aim is
      to present a multiplex method, based on MALDI-MSI, to obtain the maximum
      information from skin tissue sections. Various matrices were applied to skin
      tissue sections: (1) 9-aminoacridine for imaging metabolites in negative ion
      mode; (2) sinapinic acid to obtain protein distributions; (3) alpha-cyano-4
      hydroxycinnamic acid subsequent to on-tissue enzymatic digestion by trypsin,
      elastase, and pepsin, respectively, to localize the resulting peptides. Notably,
      substantial amounts of data were generated from the distributions retrieved for
      all matrices applied. Several primary metabolites, e.g. ATP, were localized and
      subsequently identified by on-tissue postsource decay measurements. Furthermore,
      maps of proteins and peptides derived from on-tissue digests were generated.
      Identification of peptides was achieved by elution with different solvents,
      mixing with alpha-cyano-4-hydroxycinnamic acid, and subsequent tandem mass
      spectrometry (MS/MS) measurements, thereby avoiding on-tissue MS/MS measurements.
      Highly abundant peptides were identified, allowing their use as internal
      calibrants in future MALDI-MSI analyses of human skin tissue sections. Elastin as
      an endogenous skin protein was identified only by use of elastase, showing the
      high potential of alternative enzymes. The results show the versatility of MALDI
      MSI in the field of skin research. This article containing a methodological
      perspective depicts the basics for a comprehensive comparison of various skin
      states.

PMID- 23138472
TI  - Comparative studies of thiol-sensitive fluorogenic probes for HAT assays.
AB  - Histone acetyltransferases (HATs) catalyze the acetylation of specific lysine
      residues in histone and nonhistone proteins. Recent studies showed that
      acetylation is widely distributed among cellular proteins, suggestive of diverse
      functions of HATs in cellular pathways. Nevertheless, currently available assays
      for HAT activity study are still quite limited. Here, we evaluated a series of
      thiol-sensitive fluorogenic compounds for the detection of the enzymatic
      activities of different HAT proteins. Upon conjugation to the thiol group of
      HSCoA, these molecules gain enhanced quantum yields and strong fluorescence,
      permitting facile quantitation of HAT activities. We investigated and compared
      the assay performances of these fluorogenic compounds for their capability as HAT
      activity reporters, including kinetics of reaction with HSCoA, influence on HAT
      activity, and fluorescence amplification factors. Our data suggest that CPM and
      coumarin maleic acid ester are excellent HAT probes owing to their fast reaction
      kinetics and dramatic fluorescence enhancement during the HAT reaction. Further,
      the microtiter plate measurements show that this fluorescent approach is robust
      and well suited for adaption to high-throughput screening of small molecule
      inhibitors of HATs, highlighting the value of this assay strategy in new drug
      discovery.

PMID- 23138473
TI  - Comment on "Electronic properties and charge transfer phenomena in Pt
      nanoparticles on gamma-Al2O3: size, shape, support, and adsorbate effects" by F.
      Behafarid et al., Phys. Chem. Chem. Phys., 2012, 14, 11766-11779.
AB  - We show how density functional theory (DFT) calculations rationalize the origin
      of high H/Pt ratio and the electronic properties of gamma-alumina supported Pt
      nanoparticles as observed in Phys. Chem. Chem. Phys., 2012, 14, 11766-11779.

PMID- 23138474
TI  - Neutral lipid composition changes in the fat bodies of engorged females
      Rhipicephalus microplus ticks in response to fungal infections.
AB  - The tick's fat body plays an essential role in energy storage and utilization.
      This study aimed to analyze the fat body neutral lipid composition in
      Rhipicephalus microplus engorged females. In the first study (physiological
      profile of untreated ticks), the lipid analysis took place over the course of 4
      days; the engorged females were incubated at optimal conditions and their fat
      bodies were dissected daily. Fat body lipid analysis after fungal infection with
      Metarhizium anisopliae sensu lato (s.l.) or Beauveria bassiana s.l. was performed
      with four groups: one without any treatment, one that was inoculated with a
      solution of 0.1 % Tween 80 in water, and two groups that were inoculated with M.
      anisopliae or B. bassiana conidial suspensions. The fat bodies were dissected 24
      and 48 h after infection. Lipid analysis was conducted by thin-layer
      chromatography on a silica plate. The results of the physiological profile showed
      that the amounts of triacylglycerol (TAG) and free cholesterol (CHO) decreased
      with time, whereas cholesterol ester (CHOE) increased on the second and fourth
      days. Following M. anisopliae or B. bassiana infection, there was an increase in
      the amount of CHO after 24 h, whereas the other lipid classes were not altered.
      M. anisopliae caused an increase in CHOE and TAG and a reduction in CHO at 48 h
      after infection; however, B. bassiana infection did not cause significant
      alterations in the concentrations of these lipids. M. anisopliae and B. bassiana
      infection changed the fat body metabolism of engorged female R. microplus ticks.
      This study provides the first report of changes in the neutral lipid composition
      of the R. microplus fat body.

PMID- 23138476
TI  - Processing, morphology, and water uptake of Nafion/ex situ Stober silica
      nanocomposite membranes as a function of particle size.
AB  - Because of the bicontinuous phase structure of Nafion with small hydrophilic
      channels, formation of composites with silica colloids to improve thermal
      stability, hydration, and proton conductivity should be influenced by size and
      surface functionality of the colloids. To test this hypothesis, we prepared
      batches of silica particles between 20 and 400 nm in diameter with narrow
      polydispersities using a modified Stober procedure. Some particles were
      subsequently surface-modified using mercaptopropyltriethoxysilane. Enough
      particles were mixed with Nafion in alcohols to achieve 5 wt % silica in the
      final membranes, which were made by casting and drying. Membrane top and bottom
      surface and cross-section morphologies were examined with AFM and SEM to
      determine how the particles were dispersed. We discovered that casting the
      membranes from dispersions with viscosities less than 65 cPs led to larger
      particles floating to the top surface of the membrane where they were easily
      dislodged from the dry membrane. Membranes cast from more viscous solutions
      exhibited homogeneous distributions of particles. Water uptake was over 60%
      higher in nanocomposites with unmodified silica particles than for Nafion and
      about 15% higher than for Nafion with in situ generated silica particles, but
      showed no trend in water uptake correlating with particle size. Surface silated
      particles of all sizes appeared to have reduced water uptake relative to Nafion
      alone.

PMID- 23138477
TI  - Numerical solutions of thin-film equations for polymer flows.
AB  - We report on the numerical implementation of thin-film equations that describe
      the capillary-driven evolution of viscous films, in two-dimensional
      configurations. After recalling the general forms and features of these
      equations, we focus on two particular cases inspired by experiments: the leveling
      of a step at the free surface of a polymer film, and the leveling of a polymer
      droplet over an identical film. In each case, we first discuss the long-term self
      similar regime reached by the numerical solution before comparing it to the
      experimental profile. The agreement between theory and experiment is excellent,
      thus providing a versatile probe for nanorheology of viscous liquids in thin-film
      geometries.

PMID- 23138478
TI  - Analysis of genetic correlations of hip height with selection indices and mature
      weight in Nelore cattle.
AB  - Body size is directly related to the productive and reproductive performance of
      beef cattle raised under free-range conditions. In an attempt to better plan
      selection criteria, avoiding extremes in body size, this study estimated the
      heritabilities and genetic correlations of yearling hip height (YH) and mature
      hip height (MH) with selection indices obtained at weaning (WI) and yearling (YI)
      and mature weight (MW). Data from 102,373 Nelore animals born between 1984 and
      2010, which belong to 263 farms that participate in genetic evaluation programmes
      of beef cattle conducted in Brazil and Paraguay, were used. The (co)variance
      components and genetic parameters were estimated by Bayesian inference in multi
      trait analysis using an animal model. The mean heritabilities for YH, MH and MW
      were 0.56 +/- 0.06, 0.47 +/- 0.02 and 0.42 +/- 0.02, respectively. The genetic
      correlation of YH with WI (0.13 +/- 0.01) and YI (0.11 +/- 0.01) was practically
      zero, whereas a higher correlation was observed with MW (0.22 +/- 0.03). Positive
      genetic correlations of medium magnitude were estimated between MH and WI and YI
      (0.23 +/- 0.01 and 0.43 +/- 0.02, respectively). On the other hand, a high
      genetic correlation (0.68 +/- 0.03) was observed between the indicator traits of
      mature body size (MH and MW). Considering the top 20 % of sire (896 sires) in
      terms of breeding values for the yearling index, the rank sire correlations
      between breeding values for MH and MW was 0.62. In general, the results indicate
      that selection based on WI and YI should not lead to important changes in YH.
      However, an undesired correlated response in mature cow height is expected,
      particularly when selection is performed using YI. Therefore, changes in the body
      structure of Nelore females can be obtained when MH and MW is used as a selection
      criterion for cows.

PMID- 23138479
TI  - High resolution UV roll-to-roll nanoimprinting of resin moulds and subsequent
      replication via thermal nanoimprint lithography.
AB  - UV roll-to-roll nanoimprinting at high resolution is still a relatively
      unexplored field of study with far-reaching application potential. One enabling
      technology that is particularly worthy of attention is mass production of high
      resolution resin moulds via UV roll-to-roll nanoimprinting at such high
      throughput and low cost that they can be used only once and disposed of or
      recycled economically. Low cost, high resolution resin moulds can greatly improve
      the production cost profile for a number of applications in biomedicine,
      nanofluidics, data storage and electronics with relatively low unit values but
      which require one or more nanoscale lithography steps. In this report, UV roll-to
      roll nanoimprinting was employed to fabricate high fidelity resin moulds with
      nanoscale as well as mixed micro- and nanoscale features down to 50 nm feature
      diameter, at up to 120 cm(2) area and at 10 m min(-1) throughput. UV roll-to-roll
      nanoimprinted resin moulds were subsequently segmented out, employed in a batch
      mode thermal nanoimprinting process, and characterized to study performance and
      demonstrate viability. The results show that high resolution mixed nanostructures
      can be faithfully replicated in PMMA on silicon substrates with minimal
      volumetric shrinkage. Process details and challenges specific to roll-to-roll
      fabrication of resin moulds are discussed at length, particularly with respect to
      the curvature uniformity of the imprint roller.

PMID- 23138480
TI  - Onconephrology: the latest frontier in the war against kidney disease.
AB  - Renal diseases in patients with cancer have many unique features, and often these
      diseases require specialized approaches. Newer cancer therapy has increased
      cancer cure rate and survival time, but such benefit is not fully realized,
      partly because of therapy-associated toxicities. Fluid and electrolyte
      abnormalities are very common in patients with cancer, as are acute and chronic
      kidney injury. With the evolving complexities of newer cancer therapies, a
      comprehensive team approach is becoming necessary. It is essential for
      nephrologists to be informed and involved in cancer care. Many nephrologists
      caring for patients with cancer in the United States have recently met and formed
      a focus group, the OncoNephrology Forum, under the American Society of
      Nephrology. This update addresses what is clinically unique about onconephrology,
      the objectives and functions of the newly formed forum, and the potential of
      onconephrology becoming a subspecialty in nephrology.

PMID- 23138481
TI  - Mast cells: subordinates or masterminds in autoimmunity?

PMID- 23138482
TI  - Monoclonal anti-PLA2R and recurrent membranous nephropathy: another piece of the
      puzzle.

PMID- 23138483
TI  - MicroRNAs regulate renal tubule maturation through modulation of Pkd1.
AB  - MicroRNAs (miRNAs) contribute to the regulation of early kidney development, but
      their role during later stages of renal tubule maturation is not well understood.
      Here, we found that ablation of the miRNA-processing enzyme Dicer from maturing
      renal tubules produces tubular and glomerular cysts in mice. Inactivation of
      Dicer is associated with downregulation of miR-200, a kidney-enriched miRNA
      family, and upregulation of the polycystic kidney disease gene Pkd1. Inhibition
      of miR-200 in cultured renal epithelial cells disrupted tubulogenesis and led to
      upregulation of Pkd1. Using bioinformatic and in vitro approaches, we found that
      miR-200b/c/429 induce post-transcriptional repression of Pkd1 through two
      conserved binding sites in the 3'-Untranslated regions of Pkd1. Overexpression of
      PKD1 in renal epithelial cells was sufficient to disrupt tubulogenesis and
      produce cyst-like structures. In conclusion, miRNAs are essential for the
      maturation of renal tubules, and Pkd1 is a target of miR-200. These results also
      suggest that miRNAs may modulate PKD1 gene dosage and play a role in the
      initiation of cystogenesis.

PMID- 23138484
TI  - Immature renal dendritic cells recruit regulatory CXCR6(+) invariant natural
      killer T cells to attenuate crescentic GN.
AB  - Immature renal dendritic cells (DCs) are protective early in murine crescentic
      GN, but the mechanisms underlying this protection are unknown. Here, depletion of
      DCs reduced the recruitment of invariant natural killer T (iNKT) cells, which
      attenuate GN, into the kidney in the early stage of experimental crescentic GN.
      More than 90% of renal iNKT cells expressed the chemokine receptor CXCR6, and
      renal DCs produced high amounts of the cognate ligand CXCL16 early after
      induction of nephritis, suggesting that renal DC-derived CXCL16 might attract
      protective CXCR6(+) iNKT cells. Consistent with this finding, CXCR6-deficient
      mice exhibited less iNKT cell recruitment and developed nephritis that was more
      severe, similar to the aggravated nephritis observed in mice depleted of immature
      DCs. Finally, adoptive transfer of CXCR6-competent NKT cells ameliorated
      nephritis. Taken together, these results suggest an immunoprotective mechanism
      involving immature DCs, CXCL16, CXCR6, and regulatory iNKT cells, which might
      stimulate the development of new therapeutic strategies for GN.

PMID- 23138485
TI  - Mechanistic insights into vascular calcification in CKD.
AB  - Cardiovascular disease begins early in the course of renal decline and is a life
      limiting problem in patients with CKD. The increased burden of cardiovascular
      disease is due, at least in part, to calcification of the vessel wall. The uremic
      milieu provides a perfect storm of risk factors for accelerated calcification,
      but elevated calcium and phosphate levels remain key to the initiation and
      progression of vascular smooth muscle cell calcification in CKD. Vascular
      calcification is a highly regulated process that involves a complex interplay
      between promoters and inhibitors of calcification and has many similarities to
      bone ossification. Here, we discuss current understanding of the process of
      vascular calcification, focusing specifically on the discrete and synergistic
      effects of calcium and phosphate in mediating vascular smooth muscle cell
      apoptosis, osteochondrocytic differentiation, vesicle release, calcification
      inhibitor expression, senescence, and death. Using our model of intact human
      vessels, factors initiating vascular calcification in vivo and the role of
      calcium and phosphate in driving accelerated calcification ex vivo are described.
      This work allows us to link clinical and basic research into a working
      theoretical model to explain the pathway of development of vascular calcification
      in CKD.

PMID- 23138486
TI  - Mast cells contribute to peripheral tolerance and attenuate autoimmune
      vasculitis.
AB  - Mast cells contribute to the modulation of the immune response, but their role in
      autoimmune renal disease is not well understood. Here, we induced autoimmunity
      resulting in focal necrotizing GN by immunizing wild-type or mast cell-deficient
      (Kit(W-sh/W-sh)) mice with myeloperoxidase. Mast cell-deficient mice exhibited
      more antimyeloperoxidase CD4+ T cells, enhanced dermal delayed-type
      hypersensitivity responses to myeloperoxidase, and more severe focal necrotizing
      GN. Furthermore, the lymph nodes draining the sites of immunization had fewer
      Tregs and reduced production of IL-10 in mice lacking mast cells. Reconstituting
      these mice with mast cells significantly increased the numbers of Tregs in the
      lymph nodes and attenuated both autoimmunity and severity of disease. After
      immunization with myeloperoxidase, mast cells migrated from the skin to the lymph
      nodes to contact Tregs. In an ex vivo assay, mast cells enhanced Treg suppression
      through IL-10. Reconstitution of mast cell-deficient mice with IL-10-deficient
      mast cells led to enhanced autoimmunity to myeloperoxidase and greater disease
      severity compared with reconstitution with IL-10-intact mast cells. Taken
      together, these studies establish a role for mast cells in mediating peripheral
      tolerance to myeloperoxidase, protecting them from the development of focal
      necrotizing GN in ANCA-associated vasculitis.

PMID- 23138487
TI  - Small RNAs have a big effect on polycystic kidney disease.

PMID- 23138490
TI  - Context for practice: cutting-edge information in novel formats.

PMID- 23138489
TI  - Aluminum citrate prevents renal injury from calcium oxalate crystal deposition.
AB  - Calcium oxalate monohydrate crystals are responsible for the kidney injury
      associated with exposure to ethylene glycol or severe hyperoxaluria. Current
      treatment strategies target the formation of calcium oxalate but not its
      interaction with kidney tissue. Because aluminum citrate blocks calcium oxalate
      binding and toxicity in human kidney cells, it may provide a different
      therapeutic approach to calcium oxalate-induced injury. Here, we tested the
      effects of aluminum citrate and sodium citrate in a Wistar rat model of acute
      high-dose ethylene glycol exposure. Aluminum citrate, but not sodium citrate,
      attenuated increases in urea nitrogen, creatinine, and the ratio of kidney to
      body weight in ethylene glycol-treated rats. Compared with ethylene glycol alone,
      the addition of aluminum citrate significantly increased the urinary excretion of
      both crystalline calcium and crystalline oxalate and decreased the deposition of
      crystals in renal tissue. In vitro, aluminum citrate interacted directly with
      oxalate crystals to inhibit their uptake by proximal tubule cells. These results
      suggest that treating with aluminum citrate attenuates renal injury in rats with
      severe ethylene glycol toxicity, apparently by inhibiting calcium oxalate's
      interaction with, and retention by, the kidney epithelium.

PMID- 23138491
TI  - Setting up a clinical study: get ready, set, and go.

PMID- 23138488
TI  - Circulating suPAR in two cohorts of primary FSGS.
AB  - Overexpression of soluble urokinase receptor (suPAR) causes pathology in animal
      models similar to primary FSGS, and one recent study demonstrated elevated levels
      of serum suPAR in patients with the disease. Here, we analyzed circulating suPAR
      levels in two cohorts of children and adults with biopsy-proven primary FSGS: 70
      patients from the North America-based FSGS clinical trial (CT) and 94 patients
      from PodoNet, the Europe-based consortium studying steroid-resistant nephrotic
      syndrome. Circulating suPAR levels were elevated in 84.3% and 55.3% of patients
      with FSGS patients in the CT and PodoNet cohorts, respectively, compared with 6%
      of controls (P<0.0001); inflammation did not account for this difference.
      Multiple regression analysis suggested that lower suPAR levels associated with
      higher estimated GFR, male sex, and treatment with mycophenolate mofetil. In the
      CT cohort, there was a positive association between the relative reduction of
      suPAR after 26 weeks of treatment and reduction of proteinuria, with higher odds
      for complete remission (P=0.04). In the PodoNet cohort, patients with an NPHS2
      mutation had higher suPAR levels than those without a mutation. In conclusion,
      suPAR levels are elevated in geographically and ethnically diverse patients with
      FSGS and do not reflect a nonspecific proinflammatory milieu. The associations
      between a change in circulating suPAR with different therapeutic regimens and
      with remission support the role of suPAR in the pathogenesis of FSGS.

PMID- 23138492
TI  - From the chair, WOCN Wound Guidelines Task Force.

PMID- 23138493
TI  - Guideline for the management of wounds in patients with lower-extremity venous
      disease: an executive summary.
AB  - This article provides an executive summary of the lower extremity venous disease
      (LEVD) evidence-based guideline produced by the WOCN Wound Guidelines Task Force.
      The target audience for this guideline is health care professionals who
      specialize in, direct, or provide wound care for patients at risk for or with
      lower-extremity venous disease. The full guideline opens with an overview of
      definitions of LEVD, its prevalence, clinical relevance, etiology, related
      physiology and pathophysiology, and overall management goals for patients at risk
      for developing venous leg ulcers. A detailed assessment section describes how to
      conduct a full clinical history and physical examination. Two approaches to
      interventions are provided: one addresses prevention strategies to reduce the
      risk of developing LEVD with ulcers. Methods to prevent ulcer recurrence are
      summarized including compression therapy, adjunctive therapies, medications, and
      patient education. A second approach presents treatment interventions including
      wound cleansing, debridement, infection control, antibiotic use, along with
      management of the periwound skin, nutrition, pain, and edema. This section also
      discusses limb elevation, surgical options, adjunctive therapies, patient
      education, and health care provider follow-up. A comprehensive reference list,
      glossary of terms, and appendices on cellulitis and venous eczema, types of
      edema, and compression therapy are available at the end of the guideline. This
      article provides an executive summary of the essential features of the guideline.

PMID- 23138495
TI  - Learn the language when preparing for the WOCNCB Continence Exam.

PMID- 23138496
TI  - Treatment of chronic lower extremity wound pain with nitroglycerin ointment.
AB  - BACKGROUND: The pain associated with chronic lower extremity wounds is often a
      greater concern to the patient than the condition of the wounds themselves.
      Anecdotal references regarding the use of topical nitroglycerin ointment for
      lower extremity pain are frequently encountered when discussing treatment options
      with other wound care specialists but no specific dosing information was found
      after searching current literature. CASE DESCRIPTION: Three men (aged 65-80
      years) with peripheral vascular disease and lower extremity ulcers achieved pain
      relief and improved sleep patterns following treatment with nitroglycerin
      ointment applied below the knee of the affected limb. CONCLUSION: Our limited
      experience suggests that the use of nitroglycerin ointment for lower extremity
      wound pain is safe and effective. Further studies are needed to evaluate this
      treatment for efficacy and effectiveness.

PMID- 23138498
TI  - Statins may reduce femoral osteolysis in patients with total Hip arthroplasty.
AB  - In experimental studies, statin use has been associated with reduction of
      osteoclastic activity and promotion of bone formation around implants. Moreover,
      a large clinical study recently reported a substantially reduced risk of revision
      for aseptic loosening among statin users with THA. Our objective was to evaluate
      the influence of statin use on the development of femoral osteolysis within 5
      years after THA. We conducted a case-cohort study including all THAs presenting
      with femoral osteolysis at the 5 year visit (cases) and compared them with those
      without osteolysis (controls). Cases and controls were identified from a cohort
      of primary THAs operated between 2001 and 2005. Seven hundred thirty-five THAs
      were included, mean age 68 years. Five years after surgery osteolysis had
      developed around the femoral component of 40 THAs (5.4%). Ever-use of statins was
      much less frequent among cases (5 of 40, 12.5%) than among controls (199 of 695,
      28.6%). The crude risk ratio of femoral osteolysis among statin users was 0.36
      (95% CI 0.14; 0.92). After adjusting for age, sex, activity level, BMI,
      diagnosis, bearing surface, and type of stem, the adjusted risk ratio was 0.38
      (95% CI 0.15; 0.99). In conclusion, statin use was associated with a reduced risk
      of developing femoral osteolysis 5 years after THA. Statins may be useful for
      reducing the risk of implant failure following THA.

PMID- 23138499
TI  - How virtue ethics informs medical professionalism.
AB  - We argue that a turn toward virtue ethics as a way of understanding medical
      professionalism represents both a valuable corrective and a missed opportunity.
      We look at three ways in which a closer appeal to virtue ethics could help
      address current problems or issues in professionalism education-first, balancing
      professionalism training with demands for professional virtues as a prerequisite;
      second, preventing demands for the demonstrable achievement of competencies from
      working against ideal professionalism education as lifelong learning; and third,
      avoiding temptations to dismiss moral distress as a mere "hidden curriculum"
      problem. As a further demonstration of how best to approach a lifelong practice
      of medical virtue, we will examine altruism as a mean between the extremes of
      self-sacrifice and selfishness.

PMID- 23138500
TI  - Treatment patterns, treatment satisfaction, severity of disease problems, and
      quality of life in patients with psoriasis in three Nordic countries.
AB  - Biological drugs are expensive, but can reduce symptoms and increase quality of
      life for patients with psoriasis. The aim of this study was to examine quality of
      life, disease severity and treatment satisfaction in Danish, Finnish and Swedish
      patients with psoriasis. Based on 12 months' data from patient surveys and chart
      reviews, 3 treatment groups were identified: topical, systemic and/or biological
      <12 months, and biological for 12 months. Regression analyses were performed to
      investigate influence on treatment satisfaction, disease problems and quality of
      life. Patients treated with biological drugs for 12 months showed the highest
      treatment satisfaction and the lowest Dermatology Life Quality Index score. A
      number of patients with topical treatment reported low quality of life, severe or
      very severe disease problems, and low treatment satisfaction. Some patients with
      psoriasis may be under-treated and might benefit from a more aggressive treatment
      strategy. It is important, however, that resource utilization is optimized and
      patients are not treated with more advanced agents than necessary.

PMID- 23138501
TI  - Mussel-inspired functionalization of graphene for synthesizing Ag-polydopamine
      graphene nanosheets as antibacterial materials.
AB  - Mussels have been shown to attach to virtually all types of inorganic and organic
      surfaces via their adhesive proteins. The adhesive proteins secreted by mussels
      contain high concentrations of catechol and amine functional groups, which have
      similar functional groups with polydopamine (PDA). Inspired by mussels, a mild
      and environmentally friendly method was used to synthesize Ag nanoparticles (Ag
      NPs) on functionalized PDA-graphene nanosheets (PDA-GNS) with uniform and high
      dispersion. First, a uniform layer of PDA was coated on graphene oxide (GO) by
      polymerizing dopamine (DA) at room temperature. During the process GO was reduced
      by the DA. The PDA layer on the surface of GNS can be used as a nanoscale guide
      to form uniform Ag NPs on the surface of PDA-GNS. The obtained Ag-PDA-GNS hybrid
      materials are characterized by atomic force microscopy, transmission electron
      microscopy, UV-vis spectroscopy, Raman spectroscopy, X-ray photo-electron
      spectroscopy, X-ray diffraction, and thermal gravimetric analysis. The resultant
      Ag-PDA-GNS hybrid materials exhibited strong antibacterial properties to both
      Gram-negative and Gram-positive bacteria due to the synergistic effect of GNS and
      Ag NPs.

PMID- 23138502
TI  - A new layered triangular antiferromagnet Li4FeSbO6: spin order, field-induced
      transitions and anomalous critical behavior.
AB  - Structure, electrochemical, magnetic and resonance properties of new layered
      antimonate Li(4)FeSbO(6) were comprehensively studied using powder X-ray
      diffraction, cyclic voltammetry, magnetic susceptibility, heat capacity, electron
      spin resonance and Mossbauer spectroscopy. In the crystal structure the iron ions
      form the triangular network within (LiFeSbO(6))(3-) layers alternating with
      nonmagnetic lithium layers. The electrochemical activity studied implies an
      Fe(3+)/Fe(4+) redox couple at 4.3 V (ox.) and 3.9 V (red.) thereby revealing that
      Li can be reversibly extracted. The long-range antiferromagnetic order was found
      to occur at the Neel temperature, T(N) ~ 3.6 K, confirmed both by the magnetic
      susceptibility data and specific heat ones. The effective magnetic moment is
      estimated to be 5.93 MU(B)/f.u. and satisfactorily agrees with theoretical
      estimations assuming high-spin configuration of Fe(3+) (S = 5/2). In the
      magnetically ordered state, though, the magnetization demonstrates rather
      peculiar behavior. An additional anomaly on the M(T) curves appears at T(2) <
      T(N) in moderate magnetic field. The positions of transitions at T(N) and T(2)
      separate increasingly with increasing external field. Multiple measurements
      consistently demonstrated field-sensitive moving of magnetic phase boundaries
      constituting a unique phase diagram for the compound under study. The complex low
      dimensional (2D) nature of magnetic coupling was confirmed by the dynamic
      magnetic properties study. Electron spin resonance from Fe(3+) ions in
      paramagnetic phase is characterized by a temperature independent effective g
      factor of 1.99 +/- 0.01. However, the distortion and broadening of the ESR line
      were found to take place upon approaching the magnetically ordered state from
      above. The divergence of the temperature-dependent linewidth is analyzed in terms
      of both critical behavior close to long-range magnetic order and the Berezinskii
      Kosterlitz-Thouless (BKT)-type transition. Heat capacity measurements even at
      zero field manifested an appearance of the additional anomaly at temperatures
      below the Neel temperature. The temperature dependence of ESR intensity,
      linewidth and shift of the resonant field imply an extended region of short-range
      order correlations in the compound studied. The rich variety of the anomalies in
      magnetic and resonance properties makes this new antimonate a very interesting
      system to investigate the multiple phase transitions and competing exchange
      interaction due to the critical role of the layered structure organization
      accompanied by the frustration effects in triangular antiferromagnets.

PMID- 23138503
TI  - Non-synonymous polymorphisms in the P2RX ( 4 ) are related to bone mineral
      density and osteoporosis risk in a cohort of Dutch fracture patients.
AB  - In the present study we investigated whether single nucleotide polymorphisms
      (SNPs) in the P2RX ( 4 ), which alter the P2X ( 4 ) R function, are associated
      with the development of osteoporosis and whether an interaction between the P2X (
      4 ) R and P2X ( 7 ) R confer a synergistic effect of these two receptors on
      osteoporosis risk. Patients with fracture (690 females and 231 males, aged >=50
      years) were genotyped for three non-synonymous P2X ( 4 ) R SNPs. Bone mineral
      density (BMD) was measured at the total hip, lumbar spine, and femoral neck.
      Subject carrying the variant allele of the Tyr315Cys polymorphism showed a 2.68
      fold (95 % CI, 1.20-6.02) higher risk of osteoporosis compared with wild-type
      subject. Furthermore, significant lower lumbar spine BMD values were observed in
      subjects carrying the Cys315 allele as compared with wild-type (0.85 +/- 0.17 and
      0.93 +/- 0.17 g/cm(2), respectively; p < 0.001). Assuming a recessive model,
      carriers of the variant allele of the Ser242Gly polymorphism showed increased BMD
      values at the lumbar spine compare to wild-type subject (1.11 +/- 0.35 and 0.92
      +/- 0.17 g/cm(2), respectively; p = 0.0045). This is the first study
      demonstrating an association of non-synonymous polymorphisms in the P2RX ( 4 )
      and the risk of osteoporosis, suggesting a role of the P2X ( 4 ) R in the
      regulation of bone mass.

PMID- 23138505
TI  - Partial gastric necrosis due to acute gastric volvulus secondary to agenesis of
      the gastrocolic ligament.

PMID- 23138504
TI  - The Risser sign for forensic age estimation in living individuals: a study of 643
      pelvic radiographs.
AB  - Due to increasing international migratory movements, forensic age estimations of
      living individuals in criminal proceedings are gaining increasing significance
      for forensic physicians and radiologists involved in delivering expert opinions.
      The present study examines the suitability of the radiologically well-known
      Risser sign grading as a possible new criterion in forensic age diagnostics. For
      this purpose, anteroposterior pelvic radiographs of 643 patients aged between 10
      and 30 years were retrospectively evaluated by means of two different Risser sign
      grading systems (US and French), each with 5 stages. The left and right sides of
      the pelvis were assessed separately. The data was analyzed with separation of the
      sexes. Reliable Risser sign determination was possible in 566 cases. In both
      sexes, stage 4 of both the US and the French grading systems was predominantly
      first noted at age 14 years. In the US grading system, stage 5 was also first
      achieved at age 14 years in the majority of both sexes. In the French grading
      system, females manifested stage 5 at a minimum of 16 years, whereas in males it
      was first observed at 17 years. As to the nature of iliac crest maturation,
      interesting deviations were observed at stages 1 and 5, raising doubts about
      Risser's ossification process. To conclude, both Risser sign grading systems are
      suitable for forensic age diagnostics, especially to determine whether the 14th
      year of life has been completed or not. The French Risser sign system
      additionally allows for statements as to the completion of the 16th year of age.

PMID- 23138506
TI  - The use of weighted and scored risk assessment models for venous thromboembolism.
AB  - Formalised risk assessment models (RAMs) for venous thromboembolism (VTE) using
      weighted and scored variables have only recently been widely incorporated into
      international antithrombotic guidelines. Scored and weighted VTE RAMs have
      advantages over a simplified group-specific VTE risk approach, with the potential
      to allow more tailored strategies for thromboprophylaxis and an improved
      estimation of the risk/benefit profile for a particular patient. The derivation
      of VTE RAMs should be based on variables that are  a priori  defined or
      identified in a univariate analysis and the predictive capability of each
      variable should be rigorously assessed for both clinical and statistical
      significance and internal consistency and completeness. The assessment of the RAM
      should include the goodness of fit of the model and construction of a prognostic
      index score. Any VTE RAM which has been derived must undergo validation of that
      model before it can be used in clinical practice. Validation of the model should
      be performed in a "deliberate" prospective fashion across several diverse
      clinical sites using pre-defined criteria using basic standards for performing
      model validation. We discuss the basic concepts in the derivation of recent
      scored and weighted VTE RAMs in hospitalised surgical and medical patients and
      cancer outpatients, the mechanisms for accurate external validation of the
      models, and implications for their use in clinical practice.

PMID- 23138507
TI  - Towards tailored assays for cell-based approaches to toxicity testing.
AB  - The call for a new toxicology is mainly a call for cellular approaches and their
      computational integration. This article reflects on cell models, which are
      necessary to facilitate the transition. A mechanistic perspective has prompted
      the characterization of toxicity pathways and toxicity networks in order to
      develop robust cell-based assays for toxicity testing. Differing use scenarios
      for cell systems require higher degrees of sophistication, e.g., human-on-a-chip
      approaches are based on complex organotypic cultures to approximate the
      repertoire of human physiological reactions and high-throughput tests require
      simplicity and robustness. The new paradigm emerging under the branding of
      Toxicology for the 21(st) Century needs complex models for pathway of toxicity
      identification and simpler assays for testing the perturbation of any given
      pathway. With increasing knowledge about underlying mechanisms, the needs for
      complexity and test specificity will change. Selective cell-based assays are
      desirable, especially for the detection of novel toxicants and biothreats.
      Examples from endocrine disruption, pyrogenicity, and especially shellfish toxin
      testing are used to illustrate such developments.

PMID- 23138508
TI  - Novel technologies and an overall strategy to allow hazard assessment and risk
      prediction of chemicals, cosmetics, and drugs with animal-free methods.
AB  - Several alternative methods to replace animal experiments have been accepted by
      legal bodies. An even larger number of tests are under development or already in
      use for non-regulatory applications or for the generation of information stored
      in proprietary knowledge bases. The next step for the use of the different in
      vitro methods is their combination into integrated testing strategies (ITS) to
      get closer to the overall goal of predictive "in vitro-based risk evaluation
      processes." We introduce here a conceptual framework as the basis for future ITS
      and their use for risk evaluation without animal experiments. The framework
      allows incorporation of both individual tests and already integrated approaches.
      Illustrative examples for elements to be incorporated are drawn from the session
      "Innovative technologies" at the 8th World Congress on Alternatives and Animal
      Use in the Life Sciences, held in Montreal, 2011. For instance, LUHMES cells
      (conditionally immortalized human neurons) were presented as an example for a 2D
      cell system. The novel 3D platform developed by InSphero was chosen as an example
      for the design and use of scaffold-free, organotypic microtissues. The
      identification of critical pathways of toxicity (PoT) may be facilitated by
      approaches exemplified by the MatTek 3D model for human epithelial tissues with
      engineered toxicological reporter functions. The important role of in silico
      methods and of modeling based on various pre-existing data is demonstrated by
      Altamira's comprehensive approach to predicting a molecule's potential for skin
      irritancy. A final example demonstrates how natural variation in human genetics
      may be overcome using data analytic (pattern recognition) techniques borrowed
      from computer science and statistics. The overall hazard and risk assessment
      strategy integrating these different examples has been compiled in a graphical
      work flow.

PMID- 23138509
TI  - Development, validation and testing of a human tissue engineered hypertrophic
      scar model.
AB  - Adverse hypertrophic scars can form after healing of full-thickness skin wounds.
      Currently, reliable animal and in vitro models to identify and test novel scar
      reducing therapeutics are scarce. Here we describe the development and validation
      of a tissue-engineered human hypertrophic scar (HTscar) model based on
      reconstructed epidermis on a dermal matrix containing adipose derived mesenchymal
      stem cells (ASC). Although obtained from normal, healthy skin, ASC, in contrast
      to dermal mesenchymal cells, were found to facilitate HTscar formation.
      Quantifiable HTscar parameters were identified: contraction; thickness of dermis,
      collagen-1 secretion, epidermal outgrowth, epidermal thickness, and cytokine
      secretion (IL-6, CXCL8). The model was validated with therapeutics currently used
      for treating scars (5-fluorouracil, triamcinolon) and a therapeutic known to be
      unsuccessful in scar reduction (1,25-dihydroxyvitamin-D3). Furthermore, it was
      shown that atorvastatin, but not retinoic-acid, may provide a suitable
      alternative for scar treatment. Each therapeutic selectively affected a different
      combination of parameters, suggesting combined therapy may be most beneficial.
      This animal-free hypertrophic scar model may provide an alternative model for
      mechanistic studies as well as a novel in vitro means to test anti-scar
      therapeutics, thereby reducing the use of animals.

PMID- 23138510
TI  - The ox-foot-model for investigating endoluminal thermal treatment modalities of
      varicosis vein diseases.
AB  - The introduction of technical surgical innovations in clinical medicine is
      preceded by preclinical evaluation of prototypes. Surgical aspects such as energy
      dependent tissue response and tissue sealing to reduce bleeding are usually
      investigated in animal experiments. Extra-corporal organ models can provide the
      required experimental information without harming animals and thus reduce or even
      replace in vivo experiments. Here we describe the ex vivo ox-foot-model, which
      can be used for surgical investigations and for training purposes. In the ox-foot
      model the vein remains in its anatomical bed under reproducible experimental
      conditions, i.e., blood perfusion, blood pressure, and temperature. Innovative
      endoluminal surgical procedures using laser light and radio frequency for
      varicosis treatment were tested. Treatment parameters were investigated
      systematically in a large number of samples. A standardized preclinical testing
      procedure could be established and optimized on the basis of acute macroscopic
      and histological findings. Further, optical coherence tomography could be
      evaluated as a time-saving diagnostic tool. The ox-foot-model is suitable for
      training surgical techniques relevant for the treatment of varicosis veins. It is
      a cost-effective alternative to conventional in vivo experiments, providing
      standardized experimental conditions and reproducible experimental results while
      respecting the Principles of Humane Experimental Techniques: Reduction,
      Refinement, and Replacement of animal experiments.

PMID- 23138511
TI  - The use of biomarkers of toxicity for integrating in vitro hazard estimates into
      risk assessment for humans.
AB  - The role that in vitro systems can play in toxicological risk assessment is
      determined by the appropriateness of the chosen methods, with respect to the way
      in which in vitro data can be extrapolated to the in vivo situation. This report
      presents the results of a workshop aimed at better defining the use of in vitro
      derived biomarkers of toxicity (BoT) and determining the place these data can
      have in human risk assessment. As a result, a conceptual framework is presented
      for the incorporation of in vitro-derived toxicity data into the risk assessment
      process. The selection of BoT takes into account that they need to distinguish
      adverse and adaptive changes in cells. The framework defines the place of in
      vitro systems in the context of data on exposure, structural and physico-chemical
      properties, and toxicodynamic and biokinetic modeling. It outlines the
      determination of a proper point-of-departure (PoD) for in vitro-in vivo
      extrapolation, allowing implementation in risk assessment procedures. A BoT will
      need to take into account both the dynamics and the kinetics of the compound in
      the in vitro systems. For the implementation of the proposed framework it will be
      necessary to collect and collate data from existing literature and new in vitro
      test systems, as well as to categorize biomarkers of toxicity and their relation
      to pathways-of-toxicity. Moreover, data selection and integration need to be
      driven by their usefulness in a quantitative in vitro-in vivo extrapolation
      (QIVIVE).

PMID- 23138512
TI  - Human AB serum as an alternative to fetal bovine serum for endothelial and cancer
      cell culture.

PMID- 23138517
TI  - Outcomes of a Dutch workshop on improvements for the 3Rs in daily practice.
AB  - This article describes the outcome of a workshop that was held to generate new
      ideas to improve the use of the 3R principles in science. The participants of the
      workshop represented Dutch researchers, Animal Welfare Officers, and members of
      Animal Ethics Committees from various affiliations, including academia, industry,
      contract research organizations, and knowledge centers in the Netherlands. The
      workshop resulted in six diverse consensus statements, which are presented and
      discussed in this article. The results show that there is no single,
      straightforward solution to improving the implementation of 3R methods in animal
      based research and that further improvement in 3Rs practice requires a more multi
      and interdisciplinary awareness and approach.

PMID- 23138518
TI  - A parallel design study to assess the bioequivalence of generic and branded
      hydroxychloroquine sulfate tablets in healthy volunteers.
AB  - Hydroxychloroquine (HCQ) is a racemic 4-aminoquinoline derivative that was first
      introduced as an antimalarial, and subsequently applied to the treatment of
      autoimmune diseases such as rheumatoid arthritis and systemic lupus
      erythematosus. Information on the pharmacokinetics of HCQ in healthy volunteers,
      especially in a Chinese population is limited, and this study was conducted to
      provide support for a generic product to obtain marketing authorization in
      China.The aim of the present study was to compare the pharmacokinetics and assess
      bioequivalence of a new generic test and the branded reference hydroxychloroquine
      sulfate tablets in healthy volunteers.This was a parallel, open-label,
      randomized, single-dose, 1-period fasting study. 54 healthy subjects were
      randomly assigned (1:1) to receive 200 mg hydroxychloroquine sulfate tablets of
      the test or the reference formulation. 15 blood samples were collected and whole
      blood concentrations of HCQ were determined by a validated liquid chromatography
      isotopic dilution mass spectrometry method. Log-transformed Cmax and AUC0-24
      values were used to test for bioequivalence. The 2 formulations were considered
      bioequivalent if 90% confidence intervals (CIs) for the log-transformed ratios of
      Cmax and AUC0-24 were within the predetermined bioequivalence range of 80-125%.
      Tolerability was evaluated throughout the study by vital signs, physical
      examinations, clinical laboratory tests, 12-lead electrocardiograms, and
      interviews with the subjects about adverse events.54 healthy subjects were
      enrolled and completed the study (mean [SD] age, height, body weight, and BMI
      were 23.9 [2.4] years, 168.9 [5.0] cm, 61.3 [5.4] kg, and 21.5 [1.7] kg/m2), 27
      subjects per group. No formulation or sequence effects were observed. The mean
      values of Cmax and AUC0-24 for the test and reference formulations of HCQ (197.6
      and 199.0 ng/mL, 2460.1 and 2468.3 ng/mL/h) were not significantly different. The
      90% CIs of the ratios of Cmax and AUC0-24 were 99.3% (98.1-102.1%), 99.7% (98.9
      101.4%), respectively. 4 subjects (7.41%) experienced a total of 4 mild AEs
      (headache and microscopic hematuria, 1 each; and increase in plasma
      triglycerides, 2).The results of this study suggest that the test and reference
      hydroxychloroquine sulfate tablets are bioequivalent. Both formulations were
      generally well tolerated.

PMID- 23138519
TI  - Simultaneous determination of methotrexate, dasatinib and its active metabolite N
      deshydroxyethyl dasatinib in rat plasma by LC-MS/MS: method validation and
      application to pharmacokinetic study.
AB  - Dasatinib is a multi-kinase inhibitor that potently inhibits Bcr-Abl, Src family
      and platelet-derived growth factor receptor kinases. Methotrexate is an
      antimetabolite and antifolate drug. Clinical trials utilizing a combination of
      dasatinib and methotrexate in patients with Philadelphia chromosome positive
      and/or Bcr-Abl positive acute lymphoblastic leukemia are currently ongoing. A
      need therefore exists to develop a sensitive analytical method for determination
      of dasatinib and methotrexate in plasma.To estimate methotrexate, dasatinib and
      its active metabolite N-deshydroxyethyl dasatinib simultaneously using liquid
      chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS)
      in Wistar rat plasma.The analytes were extracted by using liquid-liquid
      extraction procedure and separated on a reverse phase C18 column (50 mm*3 mm
      i.d., 4.6 u) using methanol: 2 mM ammonium acetate buffer, pH 4.0 as mobile phase
      at a flow rate 1 mL/min in gradient mode. Selective reaction monitoring was
      performed using the transitions m/z 455.0>175.0, 488.1 > 401.0, 444.26>401.0, and
      271.1>- 155.0 to quantify methotrexate, dasatinib, N-deshydroxyethyl dasatinib
      and tolbutamide respectively.The method was validated over the concentration
      range of 1-1 000 ng/mL and the lower limit of quantitation was 1 ng/mL. The
      recoveries from spiked control samples were > 79% for all analytes and internal
      standard Intra- and Interday accuracy and precision of validated method were
      within the acceptable limits of < 15% at all concentration.The quantitation
      method was successfully applied for simultaneous estimation of methotrexate,
      dasatinib and N- deshydroxyethyl dasatinib in a pharmacokinetic study in Wistar
      rats.

PMID- 23138521
TI  - Stimulus-response correspondence across peripersonal space is unaffected by
      chronic unilateral limb loss.
AB  - Previous findings show an advantage in response speed when stimulus and response
      correspond spatially (i.e., the Simon effect). Chronic unilateral amputees show
      altered spatial perception near their affected hand, providing an opportunity to
      investigate whether experience also affects the visuomotor stimulus-response (S
      R) mapping that underlies the Simon effect. We used a two-alternative, forced
      choice paradigm to probe the spatial correspondence between visual cues and
      responses, in 14 unilateral upper limb amputees and 14 matched controls. We
      presented visual stimuli in 5 different locations within peripersonal space,
      including the midline, and found a smooth gradient of S-R correspondence effects.
      This is consistent with the hypothesis that S-R correspondence is represented
      along a spatial gradient. Unilateral amputees performed indistinguishably from
      matched controls, regardless of whether stimuli appeared in the hemispace ipsi-
      or contralateral to their missing limbs. This is inconsistent with the hypothesis
      that experience-dependent visual distortions entail changes in the S-R mapping;
      alternatively, it could reflect a complete experience independence of the Simon
      effect. We propose that the affordance competition hypothesis (Cisek in Philos
      Trans R Soc B Biol Sci 362:1585-1599, 2007) explains the Simon effect and the
      underlying gradient of S-R correspondence.

PMID- 23138522
TI  - Influence of rTMS over the left primary motor cortex on initiation and
      performance of a simple movement executed with the contralateral arm in healthy
      volunteers.
AB  - Repetitive transcranial magnetic stimulation (rTMS) affects cortical excitability
      according to the frequency of stimulation. Few data are available on the
      influence of rTMS applied over the primary motor cortex (M1) on motor
      performances in healthy volunteers. The aim of this study was to determine,
      through kinematic analysis, whether rTMS over the left M1 changes initiation and
      performance of movement executed with the contralateral arm. Nine healthy males
      completed a set of motor tasks, consisting of a single-joint rapid movement
      between two objects performed under three different behavioral conditions (self
      initiated; externally triggered known, during which the subject could see where
      the target was positioned in advance; externally triggered unknown, during which
      the subject could not see where the target was positioned until he reached it).
      The tasks were performed in a randomized order in three different sessions, with
      a seven-day interval between each session: (1) without stimulation (baseline);
      (2) immediately after 1-Hz rTMS; (3) immediately after 10-Hz rTMS. We measured
      reaction time, movement time, calculated as the sum of the time taken to reach
      the target from movement onset (T1) and that taken to reach the target to
      movement termination (T2), acceleration and deceleration time on the velocity
      profile, as well as the ratio between them, and maximum speed and maximum
      acceleration. Reaction time, movement time, and T2 significantly increased after
      1-Hz rTMS and decreased after 10-Hz rTMS, while the other parameters remained
      unchanged. Our results suggest that rTMS may modify both initiation and
      performance of a voluntary movement.

PMID- 23138523
TI  - Constraining movement alters the recruitment of motor processes in mental
      rotation.
AB  - Does mental rotation depend on the readiness to act? Recent evidence indicates
      that the involvement of motor processes in mental rotation is experience
      dependent, suggesting that different levels of expertise in sensorimotor
      interactions lead to different strategies to solve mental rotation problems.
      Specifically, experts in motor activities perceive spatial material as objects
      that can be acted upon, triggering covert simulation of rotations. Because action
      simulation depends on the readiness to act, movement restriction should therefore
      disrupt mental rotation performance in individuals favoring motor processes. In
      this experiment, wrestlers and non-athletes judged whether pairs of three
      dimensional stimuli were identical or different, with their hands either
      constrained or unconstrained. Wrestlers showed higher performance than controls
      in the rotation of geometric stimuli, but this difference disappeared when their
      hands were constrained. However, movement restriction had similar consequences
      for both groups in the rotation of hands. These findings suggest that expert's
      advantage in mental rotation of abstract objects is based on the readiness to
      act, even when physical manipulation is impossible.

PMID- 23138524
TI  - Metal-doped carbon nanotubes interacting with vitamin C.
AB  - In this paper, the structural, electronic and magnetic properties of carbon
      nanotubes doped with Al, Fe, Mn and Ti atoms interacting with vitamin C molecules
      are studied through first principles simulations based on the density functional
      theory. The charge transfers are obtained from the vitamins into the tubes for
      adsorption and substitutional doping cases. The highest binding energies of
      vitamin C molecules are calculated for the Al substitutional and Ti adsorbed
      cases, with values of about 1.20 and 3.26 eV, respectively. The results
      demonstrated that, depending on doping, the spin polarizations and the
      conductance characters of the systems can change, which could be relevant to
      improve the molecule adsorption on carbon nanostructures.

PMID- 23138525
TI  - Unplanned cigarette purchases and tobacco point of sale advertising: a potential
      barrier to smoking cessation.
AB  - BACKGROUND: In the USA, tobacco marketing expenditure is increasingly
      concentrated at the point of sale (POS). Previous studies have demonstrated an
      association between exposure to tobacco POS advertising and increased smoking
      initiation, but limited evidence is available on adult smokers' decisions and
      behaviours. METHODS: An immediate post-cigarette purchase survey was administered
      to 301 cigarette purchasers outside of two grocery stores in Vermont to assess
      the prevalence of unplanned purchases and opinions about POS tobacco advertising
      and displays. RESULTS: In total, 11.3% of purchases were reported as unplanned.
      Certain groups were more likely to make unplanned purchases including: 18-24-year
      olds (OR: 2.1, 95% CI 1.0 to 4.4), less than daily smokers (OR: 5.6, 95% CI 1.9
      to 16.9), smokers who made 3+ quit attempts in the previous year (OR: 2.4, 95% CI
      0.9 to 6.0), those who plan to quit in the next month (OR: 3.7, 95% CI 1.6 to
      9.0), and those who agreed that tobacco POS advertising makes quitting smoking
      harder (OR: 2.3, 95% CI 1.1 to 4.8). Overall, 31.2% of participants agreed that
      tobacco POS advertising makes quitting smoking harder. Individuals who intended
      to quit within the next month, made 3+ quit attempts in the last year, or made an
      unplanned cigarette purchase were the most likely to agree. CONCLUSIONS: Young
      adults and individuals making multiple quit attempts or planning to quit in the
      next month are more likely to make unplanned cigarette purchases. Reducing
      unplanned purchases prompted by tobacco POS advertising could improve the
      likelihood of successful cessation among smokers.

PMID- 23138526
TI  - Availability and range of tobacco products for sale in Massachusetts pharmacies.
AB  - OBJECTIVE: New tobacco control policies have been introduced in Massachusetts
      which restrict tobacco product sales in pharmacies. The purpose of this
      investigation was to outline the scope of pharmacy involvement in the tobacco
      market by assessing the availability and range of tobacco products sold in
      Massachusetts pharmacies. METHODS: Public listings of licenced pharmacies and
      tobacco retailers in Massachusetts were examined to determine the proportion of
      pharmacies licenced to sell tobacco, and the proportion of tobacco retailers
      possessing a pharmacy licence. Telephone interviews were conducted with a random
      sample (n=70) of pharmacies possessing a tobacco licence to assess the
      availability and range of tobacco products for sale. The availability of nicotine
      replacement therapy (NRT) products was assessed as a comparison. RESULTS: The
      majority of pharmacies in Massachusetts possessed a tobacco licence (69%), and
      pharmacies made up 9% of licenced tobacco retailers. Among pharmacies surveyed
      that reported selling tobacco (90%), cigarettes were the most available tobacco
      product for sale (100%), followed by cigars (69%), little cigars/cigarillos
      (66%), moist snuff (53%), pipe tobacco (49%), roll-your-own tobacco (34%), snus
      (14%), dissolvable tobacco (11%) and electronic cigarettes (2%). Nearly all
      pharmacies selling tobacco offered the nicotine patch (100%), gum (100%) and
      lozenge (98%). CONCLUSIONS: Tobacco-free pharmacy policies would affect a
      majority of Massachusetts pharmacies and remove a variety of tobacco products
      from their store shelves. Further, nearly one in ten tobacco retailers would be
      eliminated by prohibiting tobacco sales in Massachusetts pharmacies statewide.

PMID- 23138527
TI  - Identification of COL6A2 mutations in progressive myoclonus epilepsy syndrome.
AB  - In this study, a consanguineous family with progressive myoclonus epilepsy (PME)
      was clinically examined and molecularly investigated to determine the molecular
      events causing disease. Since exclusion of known genes indicated that novel genes
      causing PME still remained unidentified, homozygosity mapping, exome sequencing,
      as well as validation and disease-segregation analyses were subsequently carried
      out for both loci and gene identification. To further assure our results, a
      muscle biopsy and gene expression analyses were additionally performed. As a
      result, a homozygous, disease-segregating COL6A2 mutation, p.Asp215Asn, absent in
      a large number of control individuals, including control individuals of Iranian
      ancestry, was identified in both affected siblings. COL6A2 was shown to be
      expressed in the human cerebral cortex and muscle biopsy revealed no specific
      histochemical pathology. We conclude that the COL6A2 p.Asp215Asn mutation is
      likely to be responsible for PME in this family; however, additional studies are
      warranted to further establish the pathogenic role of both COL6A2 and the
      extracellular proteolysis system in the pathogenesis of PME.

PMID- 23138528
TI  - Variants in GATA4 are a rare cause of familial and sporadic congenital
      diaphragmatic hernia.
AB  - Congenital diaphragmatic hernia (CDH) is characterized by incomplete formation of
      the diaphragm occurring as either an isolated defect or in association with other
      anomalies. Genetic factors including aneuploidies and copy number variants are
      important in the pathogenesis of many cases of CDH, but few single genes have
      been definitively implicated in human CDH. In this study, we used whole exome
      sequencing (WES) to identify a paternally inherited novel missense GATA4 variant
      (c.754C>T; p.R252W) in a familial case of CDH with incomplete penetrance.
      Phenotypic characterization of the family included magnetic resonance imaging of
      the chest and abdomen demonstrating asymptomatic defects in the diaphragm in the
      two "unaffected" missense variant carriers. Screening 96 additional CDH patients
      identified a de novo heterozygous GATA4 variant (c.848G>A; p.R283H) in a non
      isolated CDH patient. In summary, GATA4 is implicated in both familial and
      sporadic CDH, and our data suggests that WES may be a powerful tool to discover
      rare variants for CDH.

PMID- 23138529
TI  - Lack of differences in the pharmacokinetics of sepantronium bromide (YM155)
      between US and Japanese patients with advanced solid tumors or non-Hodgkin
      lymphoma.
AB  - The analysis was designed to compare the pharmacokinetics (PK) of sepantronium
      between US and Japanese patient populations using data obtained from two phase 1
      studies being conducted in a similar design, one conducted in the USA and the
      other in Japan. Patients with a confirmed advanced solid tumor or non-Hodgkin
      lymphoma (NHL) (US only) that were refractory to standard therapy or for which no
      standard therapy was available participated in these studies. Sepantronium
      bromide was administered as a continuous intravenous infusion for 168 h (7 days)
      every 21 days. During the first two treatment cycles, serial blood and urine
      samples were collected for up to 48 h after termination of sepantronium bromide
      infusion. Forty-one subjects in the US study (including five patients with NHL)
      and 33 patients in the Japanese study were enrolled in both studies and 35 in US
      and 32 in Japan had adequate samples for PK evaluation. The PK parameters were
      calculated by non-compartment analysis method and were compared in the US and
      Japanese populations. The geometric mean ratios (90% confidence intervals) of
      area under the concentration-time curve, steady state concentration and amount
      excreted into urine between Japanese and US populations were 1.068 (0.932-1.224),
      1.141 (0.996-1.307) and 0.981 (0.855-1.125), respectively. There appear to be no
      PK differences between the US and Japanese patients with solid tumors or NHL.

PMID- 23138530
TI  - Irrelevant sensory stimuli interfere with working memory storage: evidence from a
      computational model of prefrontal neurons.
AB  - The encoding of irrelevant stimuli into the memory store has previously been
      suggested as a mechanism of interference in working memory (e.g., Lange &
      Oberauer, Memory, 13, 333-339, 2005; Nairne, Memory & Cognition, 18, 251-269,
      1990). Recently, Bancroft and Servos (Experimental Brain Research, 208, 529-532,
      2011) used a tactile working memory task to provide experimental evidence that
      irrelevant stimuli were, in fact, encoded into working memory. In the present
      study, we replicated Bancroft and Servos's experimental findings using a
      biologically based computational model of prefrontal neurons, providing a
      neurocomputational model of overwriting in working memory. Furthermore, our
      modeling results show that inhibition acts to protect the contents of working
      memory, and they suggest a need for further experimental research into the
      capacity of vibrotactile working memory.

PMID- 23138531
TI  - Syntheses, structures, photoluminescence, photocatalysis, and photoelectronic
      effects of 3D mixed high-connected metal-organic frameworks based on octanuclear
      and dodecanuclear secondary building units.
AB  - Four novel metal-organic frameworks (MOFs) based on high-nuclear metal
      carboxylate clusters, namely, [Zn(4)(L)(2)(MU(3)-OH)(2)(H(2)O)(1.5)].2H(2)O (1),
      [Zn(5)Na(L)(2)(MU(3)-OH)(4)(CH(3)CH(2)O)(H(2)O)(2)] (2),
      [Cd(4)(L)(2)(BIME)(0.5)(MU(3)-OH)(2)(H(2)O)(1.5)].2H(2)O (3), and
      [Zn(4)(L)(2)(BET)(0.5)(MU(3)-OH)(2)(H(2)O)] (4), where H(3)L = (3,5-dicarboxyl
      phenyl)-(4-(2'-carboxyl-phenyl)-benzyl)ether, BET = 1,1'-(2'-oxybis(ethane-2,1
      diyl))bis(1,2,4-triazol-1-yl), BIME = 1,2-bis(imidazol-1-yl)ethane, have been
      synthesized under hydrothermal conditions. In 1, each planar octanuclear zinc
      cluster [Zn(8)(MU(3)-OH)(8)(CO(2))(12)(H(2)O)(3)] is linked by twelve L anions to
      give an unusual (3,12)-connected framework with (4(3))(2)(4(20).6(28).8(18))
      topology. In 2, dodecanuclear heterometallic clusters [Zn(10)Na(2)(MU(3)
      OH)(8)(CO(2))(12)(CH(3)CH(2)O)(2)(H(2)O)(4)] are surrounded by twelve L anions to
      form a (3,12)-connected net with the same topology as 1. However, 3 exhibits a
      rare (3,14)-connected (4(3))(3(2)4)(3(4).4(20).5(14).6(34).7(11).8(8)) net based
      on octanuclear cadmium cluster [Cd(8)(BIME)(2)(MU(3)
      OH)(4)(CO(2))(12)(H(2)O)(4)].2H(2)O as a 14-connected node and H(3)L as a 3
      connected node. In 4, each octanuclear zinc cluster [Zn(8)(BET)(2)(MU(3)
      OH)(4)(CO(2))(12)(H(2)O)(2)] is linked by twelve L anions to furnish a (3,14)
      connected net with the same topology as 3. The optical energy gaps and
      photoluminescence were investigated for the compounds. Moreover, compounds 1-4
      exhibit good photocatalytic activities for degradation of methylene blue (MB)
      under UV irradiation and show good stability towards UV photocatalysis. In
      addition, 1 and 4 display a photocurrent density under several on-off cycles of
      illumination.

PMID- 23138532
TI  - Neuromuscular electrical stimulation (NMES) reduces structural and functional
      losses of quadriceps muscle and improves health status in patients with knee
      osteoarthritis.
AB  - Knee osteoarthritis (OA) is associated with quadriceps atrophy and weakness, so
      muscle strengthening is an important point in the rehabilitation process. Since
      pain and joint stiffness make it often difficult to use conventional strength
      exercises, neuromuscular electrical stimulation (NMES) may be an alternative
      approach for these patients. This study was aimed at (1) identifying the
      associations of knee OA with quadriceps muscle architecture and strength, and (2)
      quantifying the effects of a NMES training program on these parameters. In phase
      1, 20 women with knee OA were compared with 10 healthy female, asymptomatic, age
      matched control subjects. In phase 2, 12 OA patients performed an 8-week NMES
      strength training program. OA patients presented smaller vastus lateralis
      thickness (11.9 mm) and fascicle length (20.5%) than healthy subjects (14.1 mm;
      24.5%), and also had a 23% smaller knee extensor torque compared to the control
      group. NMES training increased vastus lateralis thickness (from 12.6 to 14.2 mm)
      and fascicle length (from 19.6% to 24.6%). Additionally, NMES training increased
      the knee extensor torque by 8% and reduced joint pain, stiffness, and functional
      limitation. In conclusion, OA patients have decreased strength, muscle thickness,
      and fascicle length in the knee extensor musculature compared to control
      subjects. NMES training appears to offset the changes in quadriceps structure and
      function, as well as improve the health status in patients with knee OA.

PMID- 23138533
TI  - Integrated compound profiling screens identify the mitochondrial electron
      transport chain as the molecular target of the natural products manassantin,
      sesquicillin, and arctigenin.
AB  - Phenotypic compound screens can be used to identify novel targets in signaling
      pathways and disease processes, but the usefulness of these screens depends on
      the ability to quickly determine the target and mechanism of action of the
      molecules identified as hits. One fast route to discovering the mechanism of
      action of a compound is to profile its properties and to match this profile with
      those of compounds of known mechanism of action. In this work, the Novartis
      collection of over 12,000 pure natural products was screened for effects on early
      zebrafish development. The largest phenotypic class of hits, which caused
      developmental arrest without necrosis, contained known electron transport chain
      inhibitors and many compounds of unknown mechanism of action. High-throughput
      transcriptional profiling revealed that these compounds are mechanistically
      related to one another. Metabolic and biochemical assays confirmed that all of
      the molecules that induced developmental arrest without necrosis inhibited the
      electron transport chain. These experiments demonstrate that the electron
      transport chain is the target of the natural products manassantin, sesquicillin,
      and arctigenin. The overlap between the zebrafish and transcriptional profiling
      screens was not perfect, indicating that multiple profiling screens are necessary
      to fully characterize molecules of unknown function. Together, zebrafish
      screening and transcriptional profiling represent sensitive and scalable
      approaches for identifying bioactive compounds and elucidating their mechanism of
      action.

PMID- 23138534
TI  - Synthesis, cyclopolymerization and cyclo-copolymerization of 9-(2
      diallylaminoethyl)adenine and its hydrochloride salt.
AB  - We report herein the synthesis and characterization of 9-(2-diallylaminoethyl)
      adenine. We evaluated two different synthetic routes starting with adenine where
      the optimal route was achieved through coupling of 9-(2-chloroethyl)adenine with
      diallylamine. The cyclopolymerization and cyclo-copolymerization of 9-(2
      diallylaminoethyl)adenine hydrochloride salt resulted in low molecular weight
      oligomers in low yields. In contrast, 9-(2-diallylaminoethyl)adenine failed to
      cyclopolymerize, however, it formed a copolymer with SO2 in relatively good
      yields. The molecular weights of the cyclopolymers were around 1,700-6,000 g/mol,
      as estimated by SEC. The cyclo-copolymer was stable up to 226  degrees C. To the
      best of our knowledge, this is the first example of a free-radical cyclo
      copolymerization of a neutral alkyldiallylamine derivative with SO2. These
      polymers represent a novel class of carbocyclic polynucleotides.

PMID- 23138535
TI  - Investigating silver coordination to mixed chalcogen ligands.
AB  - Six silver(I) coordination complexes have been prepared and structurally
      characterised. Mixed chalcogen-donor acenaphthene ligands L1-L3
      [Acenap(EPh)(E'Ph)] (Acenap = acenaphthene-5,6-diyl; E/E' = S, Se, Te) were
      independently treated with silver(I) salts (AgBF4/AgOTf). In order to keep the
      number of variables to a minimum, all reactions were carried out using a 1:1
      ratio of Ag/L and run in dichloromethane. The nature of the donor atoms, the
      coordinating ability of the respective counter-anion and the type of solvent used
      in recrystallisation, all affect the structural architecture of the final
      silver(I) complex, generating monomeric, silver(I) complexes {[AgBF4(L)2] (1 L =
      L1; 2 L = L2; 3 L = L3), [AgOTf(L)3] (4 L = L1; 5 L = L3), [AgBF4(L)3] (2a L =
      L1; 3a L = L3)} and a 1D polymeric chain {[AgOTf(L3)](n) 6}. The organic
      acenaphthene ligands L1-L3 adopt a number of ligation modes (bis-monodentate MU2
      eta2-bridging, quasi-chelating combining monodentate and eta6-E(phenyl)-Ag(I) and
      classical monodentate coordination) with the central silver atom at the centre of
      a tetrahedral or trigonal planar coordination geometry in each case. The
      importance of weak interactions in the formation of metal-organic structures is
      also highlighted by the number of short non-covalent contacts present within each
      complex.

PMID- 23138536
TI  - Asymmetric construction of all-carbon quaternary stereocenters by chiral
      auxiliary-mediated Claisen rearrangement and total synthesis of (+)-bakuchiol.
AB  - An asymmetric Claisen rearrangement using Oppolzer&#8217;s camphorsultam  was
      developed. Under thermal conditions, a geraniol-derived substrate underwent the
      rearrangement with good stereoselectivity. The absolute configuration of the
      newly formed all-carbon quaternary stereocenter was confirmed by the total
      synthesis of (+)-bakuchiol from the rearrangement product.

PMID- 23138537
TI  - Variation of medicinal components in a unique geographical accession of horny
      goat weed Epimedium sagittatum Maxim. (Berberidaceae).
AB  - Herbal Epimedium species have been widely in Traditional Chinese Medicine for
      sexual enhancement, immunity improvement, anticancer and anti-aging treatment,
      with flavonoids and polysaccharides being the major active components. However,
      exhaustive depletion of wild sources warrants germplasm evaluation and quality
      resource exploration. A preliminarily analysis had previously indicated that a
      specific local geographic accession of Epimedium sagittatum found in Luotian (LT)
      county of Hubei Province (China) had a much higher content of total flavonoids
      and polysaccharides. In this study, we further investigated the medicinal
      component variation in the LT type under different light intensities and in
      different regions by the common-garden experiment. The results indicated a light
      intensity range of 40-160 MUmol/m2/s was the most suitable for the synthesis and
      accumulation of total flavonoids, while polysaccharide accumulation was
      negatively correlated with the light intensity. Icariin was the component
      displaying the highest content among flavonoids, and the content of major
      flavonoid bioactive components was relatively stable in the third year after
      cultivation. There was significant correlation between the major flavonol
      glycoside constituents and the geographic location, and Central China followed by
      Northern China were the highly suitable regions for cultivation of LT type E.
      sagittatum. The results revealed that there was a functional balance between
      flavonoids and polysaccharides at different developmental stages, and the best
      harvesting stage should consider the primary contents of interest. This study
      provides important information on the exploration of quality resources, further
      breeding approaches and cultivation practices of E. sagittatum, and thus the
      important insights to enhance our understanding of quality control of traditional
      medicinal plants.

PMID- 23138538
TI  - Stemless shoulder prosthesis versus conventional anatomic shoulder prosthesis in
      patients with osteoarthritis: a comparison of the functional outcome after a
      minimum of two years follow-up.
AB  - BACKGROUND: The stemless shoulder prosthesis is a new concept in shoulder
      arthroplasty. To date, only a few studies have investigated the results of this
      prosthesis. The aim of this study was to investigate the clinical and
      radiological midterm results of this implant in comparison with a standard
      anatomic stemmed shoulder prosthesis. MATERIALS AND METHODS: The Constant score,
      the DASH score, the active range of motion (abduction, anteversion, external
      rotation), and the radiological results were examined in 82 patients with primary
      osteoarthritis of the shoulder treated with either the Total Evolutive Shoulder
      System((r)) (Biomed, France) stemless shoulder prosthesis or the Affinis((r))
      (Mathys, Switzerland) stemmed shoulder prosthesis to detect possible differences
      in the functional outcome and to evaluate radiological properties of the
      implants. Patients were examined before and 32 +/- 4 months after surgery.
      RESULTS: There was no significant difference in the Constant scores of the groups
      treated with the stemless shoulder prosthesis (65.0 +/- 11.0 points) and the
      stemmed shoulder prosthesis (73.2 +/- 11.3 points; P = 0.162). The estimated
      blood loss (P = 0.026) and the mean operative time (P = 0.002) were significantly
      lower in the group with the stemless shoulder prosthesis. CONCLUSIONS: The use of
      the stemless shoulder prosthesis yielded good results which, in a mid-term follow
      up, were comparable with those provided by a standard anatomic shoulder
      prosthesis. Further investigations are needed regarding the long-term performance
      of this prosthesis.

PMID- 23138539
TI  - The ability of CBCL DSM-oriented scales to predict DSM-IV diagnoses in a referred
      sample of children and adolescents.
AB  - The majority of studies examining associations between clinical-diagnostic and
      empirical-quantitative approaches have concentrated only on the target diagnosis
      without taking into account any possible co-variation of psychopathological
      traits, which is intrinsic to child psychopathology. The ability of child
      behaviour checklist (CBCL) DSM-oriented scales (DOSs) to predict target and other
      DSM diagnoses, taking into consideration the covariation of psychopathological
      traits, was analysed by logistic regression analysis. Corresponding odds ratio
      (OR) was used as indicator of the strength of the relationship between the
      clinical score in DOSs and the presence of DSM-IV diagnoses. Logistic regression
      allowed us to consider multiple scales simultaneously, thus addressing the
      problem of co-occurrence of psychopathological traits, and to include gender and
      age as covariates. The sample consisted of 360 children and adolescents aged 6-16
      years, consecutively referred for behavioural and emotional problems. As a whole,
      the CBCL DOSs seem to be more specific but with a weaker association with DSM-IV
      diagnoses than syndrome scales, and with some distinctive features: clinical
      scores in the anxiety DOS suggest a diagnosis of both anxiety and mood disorder;
      clinical scores in the somatic problems DOS are very strong and specific
      predictors for diagnosis of separation anxiety disorder; clinical scores in the
      oppositional defiant problems DOS are not only predictors of the oppositional
      defiant disorder but are also strong predictors of generalized anxiety disorder;
      clinical scores in the conduct problems DOS are a specific and strong predictor
      for oppositional defiant disorder. Results confirm the clinical usefulness of
      CBCL and suggest using both syndrome and DOS scales for a complete and accurate
      assessment of children and adolescents.

PMID- 23138540
TI  - Fabrication of ordered bulk heterojunction organic photovoltaic cells using
      nanopatterning and electrohydrodynamic spray deposition methods.
AB  - Organic photovoltaic cells with an ordered heterojunction (OHJ) active layer are
      expected to show increased performance. In the study described here, OHJ cells
      were fabricated using a combination of nanoimprinting and electrohydrodynamic
      (EHD) spray deposition methods. After an electron donor material was
      nanoimprinted with a PDMS stamp (valley width: 230 nm, period: 590 nm) duplicated
      from a Si nanomold, an electron acceptor material was deposited onto the
      nanoimprinted donor layer using an EHD spray deposition method. The donor
      acceptor interface layer was observed by obtaining cross-sectional images with a
      focused ion beam (FIB) microscope. The photocurrent generation performance of the
      OHJ cells was evaluated with the current density-voltage curve under air mass
      (AM) 1.5 conditions. It was found that the surface morphology of the electron
      acceptor layer affected the current and voltage outputs of the photovoltaic
      cells. When an electron acceptor layer with a smooth thin (250 nm above the
      valley of the electron donor layer) surface morphology was obtained, power
      conversion efficiency was as high as 0.55%. The electrohydrodynamic spray
      deposition method used to produce OHJ photovoltaic cells provides a means for the
      adoption of large area, high throughput processes.

PMID- 23138541
TI  - Ultrafine sputter-deposited Pt nanoparticles for triiodide reduction in dye
      sensitized solar cells: impact of nanoparticle size, crystallinity and surface
      coverage on catalytic activity.
AB  - This paper presents a detailed electrochemical impedance spectroscopy and cyclic
      voltammetry (CV) investigation into the electrocatalytic activity of ultrafine
      (i.e., smaller than 2 nm) platinum (Pt) nanoparticles generated on a fluorine
      doped tin oxide (FTO) surface via room temperature tilted target sputter
      deposition. In particular, the Pt-decorated FTO electrode surfaces were tested as
      counter electrode candidates for triiodide (I3(-)) reduction in dye-sensitized
      solar cells (DSSCs). We observed a direct correlation between size-dependent Pt
      nanoparticle crystallinity and the I3(-) reduction activity underlying DSSC
      performance. CV analysis confirmed the higher electrocatalytic activities of
      sputter-deposited crystalline Pt nanoparticles (1-2 nm) compared with either sub
      nanometre Pt clusters or a continuous Pt thin film. While the low catalytic
      activity and DSSC performance of Pt clusters smaller in size than 1 nm is
      believed to arise from their non-crystalline nature and charge-trapping
      attributes, we attribute the high catalytic performance of larger Pt
      nanoparticles in the 1-2 nm regime to their well-defined crystallinity and fast
      electron transfer kinetics. For DSSC applications, the optimized Pt loading was
      calculated to be ~2.54 * 10(-7) g cm(-2), which corresponds to surface coverage
      by ~1.6 nm sized Pt nanoparticles.

PMID- 23138542
TI  - Electron-microscopy of cherry haemangioma in the early diagnosis of Fabry
      disease.

PMID- 23138543
TI  - Seizures do not increase in-hospital mortality after intracerebral hemorrhage in
      the nationwide inpatient sample.
AB  - BACKGROUND: Seizures are common after intracerebral hemorrhage (ICH) but their
      impact on outcome is uncertain and prophylactic anti-convulsant use is
      controversial. We hypothesized that seizures would not increase the risk of in
      hospital mortality in a large administrative database. METHODS: The study
      population included patients in the 2006 Nationwide Inpatient Sample over the age
      of 18 with a principal diagnosis of ICH (ICD9 = 431). Subjects with a secondary
      diagnosis of aneurysm, arterio-venous malformation, brain tumor, or traumatic
      brain injury were excluded. Seizures were defined by ICD9 codes (345.0x-345.5x,
      345.7x-345.9x, 780.39). Logistic regression was used to quantify the relationship
      between seizures and in-hospital mortality. Pre-specified subgroups included age
      strata, length of stay, and invasive procedures. RESULTS: 13,033 subjects met all
      eligibility criteria, of which 1,430 (11.0 %) had a secondary diagnosis of
      seizure. Subjects with seizure were younger (64 vs. 70 years, p < 0.001), more
      likely to get craniectomy (2.1 vs. 1.2 %, p = 0.006), ventriculostomy (8.5 vs.
      6.0 %, p < 0.001), intubation (32.2 vs. 25.9 %, p < 0.001), and tracheostomy (6.4
      vs. 4.2 %, p < 0.001). Seizure patients had lower in-hospital mortality (24.3 vs.
      28.0 %, p = 0.003). In a multivariable model incorporating patient and hospital
      level variables, seizures were associated with reduced odds of in-hospital death
      (OR = 0.62, 95 % CI 0.52-0.75). CONCLUSIONS: A secondary diagnosis of seizure
      after ICH was not associated with increased in-hospital death overall or in any
      of the pre-specified subgroups; however, there may be residual confounding by
      severity. These findings do not support a need for routine prophylactic anti
      epileptic drug use after ICH.

PMID- 23138544
TI  - Clinical prediction models for aneurysmal subarachnoid hemorrhage: a systematic
      review.
AB  - BACKGROUND: Clinical prediction models can enhance clinical decision-making and
      research. However, available prediction models in aneurysmal subarachnoid
      hemorrhage (aSAH) are rarely used. We evaluated the methodological validity of
      SAH prediction models and the relevance of the main predictors to identify
      potentially reliable models and to guide future attempts at model development.
      METHODS: We searched the EMBASE, MEDLINE, and Web of Science databases from
      January 1995 to June 2012 to identify studies that reported clinical prediction
      models for mortality and functional outcome in aSAH. Validated methods were used
      to minimize bias. RESULTS: Eleven studies were identified; 3 developed models
      from datasets of phase 3 clinical trials, the others from single hospital
      records. The median patient sample size was 340 (interquartile range 149-733).
      The main predictors used were age (n = 8), Fisher grade (n = 6), World Federation
      of Neurological Surgeons grade (n = 5), aneurysm size (n = 5), and Hunt and Hess
      grade (n = 3). Age was consistently dichotomized. Potential predictors were
      prescreened by univariate analysis in 36 % of studies. Only one study was
      penalized for model optimism. Details about model development were often
      insufficiently described and no published studies provided external validation.
      CONCLUSIONS: While clinical prediction models for aSAH use a few simple
      predictors, there are substantial methodological problems with the models and
      none have had external validation. This precludes the use of existing models for
      clinical or research purposes. We recommend further studies to develop and
      validate reliable clinical prediction models for aSAH.

PMID- 23138545
TI  - Outcome prediction in moderate and severe traumatic brain injury: a focus on
      computed tomography variables.
AB  - BACKGROUND: With this study we aimed to design validated outcome prediction
      models in moderate and severe traumatic brain injury (TBI) using demographic,
      clinical, and radiological parameters. METHODS: Seven hundred consecutive
      moderate or severe TBI patients were included in this observational prospective
      cohort study. After inclusion, clinical data were collected, initial head
      computed tomography (CT) scans were rated, and at 6 months outcome was determined
      using the extended Glasgow Outcome Scale. Multivariate binary logistic regression
      analysis was applied to evaluate the association between potential predictors and
      three different outcome endpoints. The prognostic models that resulted were
      externally validated in a national Dutch TBI cohort. RESULTS: In line with
      previous literature we identified age, pupil responses, Glasgow Coma Scale score
      and the occurrence of a hypotensive episode post-injury as predictors.
      Furthermore, several CT characteristics were associated with outcome; the aspect
      of the ambient cisterns being the most powerful. After external validation using
      Receiver Operating Characteristic (ROC) analysis our prediction models
      demonstrated adequate discriminative values, quantified by the area under the ROC
      curve, of 0.86 for death versus survival and 0.83 for unfavorable versus
      favorable outcome. Discriminative power was less for unfavorable outcome in
      survivors: 0.69. CONCLUSIONS: Outcome prediction in moderate and severe TBI might
      be improved using the models that were designed in this study. However,
      conventional demographic, clinical and CT variables proved insufficient to
      predict disability in surviving patients. The information that can be derived
      from our prediction rules is important for the selection and stratification of
      patients recruited into clinical TBI trials.

PMID- 23138547
TI  - Goal directed brain tissue oxygen monitoring versus conventional management in
      traumatic brain injury: an analysis of in hospital recovery.
AB  - BACKGROUND: Brain tissue oxygen monitoring (pBtO2) has been advocated in the
      treatment of patients with severe traumatic brain injuries (TBI); however,
      controversy exists regarding the improvements that pBtO2 monitoring provides. The
      objective of our study was to evaluate our experience and effect on mortality
      with goal directed pBtO2 monitoring for severe TBI compared to traditional
      ICP/CPP monitoring. METHODS: All patients admitted with severe TBI (GCS < 8) to
      our Level 1 trauma center from June 2007 through June 2009 were retrospectively
      analyzed. All patients had ICP monitoring and pBtO2 monitors were placed based on
      the current practices of the attending neurosurgeon producing two temporally
      matched cohorts of patients with and without pBtO2 monitors. Exclusion criteria
      were age <18 years and survival <24 h. Goal-directed therapy was utilized in all
      patients to maintain ICP <20 mmHg and CPP >60 mmHg. Patients with pBtO2 monitors
      were managed to maintain a level >20 mmHg. RESULTS: 74 patients were treated for
      severe TBI over the 2-year study period with 37 patients in each group. Both
      groups were similar in age, sex, and admission Glascow Coma Score(GCS).The pBtO2
      monitored group did, however, have significantly lower injury severity score [26
      (25-30) vs. 30 (26-36), p = 0.03] and AIS Chest [0 (0-0) vs. 2 (0-3), p = 0.02].
      There was no survival difference found (64.9 vs. 54.1 %, p = 0.34). No difference
      with respect to discharge GCS or discharge Functional Independence Measure score
      was identified. CONCLUSIONS: Compared with ICP/CPP-directed therapy alone, the
      addition of pBtO2 monitoring did not provide a survival or functional status
      improvement at discharge. The true clinical benefit of pBtO2 monitoring will
      require further study.

PMID- 23138548
TI  - [Diagnosis of fibromyalgia].

PMID- 23138546
TI  - Influenza-associated neurological complications.
AB  - While mostly diagnosed in the pediatric population, neurological complications of
      pandemic influenza A infection may affect young and previously healthy adults,
      and may follow a fulminant, severe, and occasionally fatal course. We reviewed
      severe neurological complications secondary to influenza infection reported in
      the literature, in attempt to outline recurrent syndromes that may assist the
      clinician in making a timely diagnosis. Vigilance and awareness of these clinical
      entities are key in the neurologist and intensivist's role in surveillance and
      early recognition of pandemic influenza, and in ensuring improved survival for
      affected patients.

PMID- 23138549
TI  - [Vasculitis update].

PMID- 23138550
TI  - [Revised Chapel Hill nomenclature of vasculitides].

PMID- 23138551
TI  - [Update on granulomatosis with polyangitis (GPA, Wegener's granulomatosis)].
AB  - Granulomatosis with polyangitis (GPA, Wegener's granulomatosis) is characterized
      by a granulomatous inflammation of the respiratory tract and a necrotizing ANCA
      associated small to medium-size vessel vasculitis with a predilection for the
      lungs (pulmonary capillaritis) and kidneys (necrotizing glomerulonephritis). The
      disease evolves stage-wise and typically starts as inflammation of the
      respiratory tract followed by development of systemic vasculitis manifestations.
      Today, treatment is evidence-based and adapted according to activity and disease
      stage which has resulted in a significant improvement in long-term outcome. Early
      mortality during the first year of treatment poses one of the main problems and
      is a result of infections under immunosuppressive treatment. Furthermore,
      treatment of refractory disease activity which is often represented by
      granulomatous manifestations is still a challenge and may result in significant
      organ damage if not treated successfully.

PMID- 23138552
TI  - [Giant-cell arteritis: update: diagnosis and therapy].
AB  - Giant-cell arteritis (GCA) is the most common form of vasculitis in patients over
      50 years old. Loss of vision is the most common severe complication but
      involvement of extracranial arteries including the aorta is more frequent than
      previously assumed. The role of dendritic and T-cells indicates the presence of
      an antibody but a clear association with underlying infections has not yet been
      demonstrated. Even if the inflammation parameters in blood are mostly increased
      in the diagnosis of GCA, specific laboratory tests for the diagnosis of GCA are
      not available. Of the imaging procedures ultrasonography, magnetic resonance
      imaging and (18)F-fluorodeoxyglucose positron emission tomography can be useful
      to localize and estimate the extent of vascular involvement. Glucocorticoids are
      still the standard therapy of GCA, whereby the cumulative dose can possibly be
      reduced by additional methotrexate. In addition acetylsalicylic acid is
      recommended as prophylaxis against cardiovascular and cerebrovascular events as
      well as prophylaxis and therapy of accompanying osteoporosis.

PMID- 23138553
TI  - [Update: Behcet's disease].
AB  - Behcet's disease (BD) is now mentioned in the latest Chapel Hill nomenclature of
      vasculitides and is classified under the variable vessel vasculitides (VVV).
      Pathogenetically, a new classification among the so-called mixed-pattern diseases
      between classical polygenic autoinflammatory disorders and autoimmune diseases is
      being discussed. The genetic association with HLA-B51 is undisputed and an
      association with HLA-A26 as well as with polymorphisms in the IL-10 and IL23R
      IL12RB2 genes have recently been described. Increasingly, a participation of IL
      17 in the pathogenesis of BD is assumed. Therapeutically, the EULAR
      recommendations are still applicable. Interferon-alpha can be discontinued for
      severe ocular BD in remission without further relapses. Infliximab can be
      switched to adalimumab effectively and recent case series show an efficacy of IL
      1 antagonists, tocilizumab and rituximab for BD.

PMID- 23138554
TI  - [Update Churg-Strauss syndrome].
AB  - The Churg-Strauss syndrome (CSS) is the rarest subtype of the so-called anti
      neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) and has the
      lowest frequency of ANCA-positivity (around 30%). In addition to asthma and blood
      eosinophilia, CSS is characterized by end-organ damage, which can be caused by
      either vasculitis and/or tissue infiltration of eosinophilic granulocytes. The
      CSS shares many etiological and clinical features of other hypereosinophilic
      syndromes. Recently, a distinct genetic background could be demonstrated for both
      the ANCA-positive and ANCA-negative subtypes of CSS as compared to the other two
      forms of AAV. Among other cytokines, interleukin-5 (IL-5) could be identified as
      a key mediator of eosinophilia. Therefore, recent clinical trials in CSS aimed to
      target IL-5. Outside of clinical trials, treatment of CSS is adapted to disease
      stage and activity, as recommended for other types of AAV.

PMID- 23138555
TI  - [How I treat ...].

PMID- 23138556
TI  - [Prosthesis loosening].
AB  - Prosthesis loosening is becoming more and more important due to increasing
      numbers of primary arthroplasty. Especially in patients suffering from rheumatoid
      arthritis this is a major topic due to younger age and multiple affected joints.
      A carefully performed diagnostic regimen is essential for ruling out septic
      loosening of the prosthesis. Preoperative planning is crucial for revision
      surgery. Revision implants should be available as back-up. Revision arthroplasty
      is a technically and economically demanding procedure. Costs for revision surgery
      are much higher than for primary arthroplasty due to longer hospital stay,
      intensive care, microbiology, histology, diagnostic imaging, implants and
      antibiotics. Revision arthroplasty should be performed in highly specialized
      centers.

PMID- 23138557
TI  - [Glycosylation-dependent effector function of IgG antibodies].
AB  - The Fc fragments of pathogenic IgG autoantibodies in patients with rheumatoid
      arthritis are low-galactosylated and low-sialylated. In contrast, high
      galactosylated and high-sialylated antigen-specific IgG antibodies are sufficient
      to inhibit a pro-inflammatory immune response in an antigen-specific manner and
      might be a promising therapeutic tool to re-establish tolerance against defined
      self-antigens in autoimmune patients.

PMID- 23138560
TI  - Functional expression of ERG1 potassium channels in rat alveolar macrophages.
AB  - Alveolar macrophages (AMs) play a vital role in lung immunity. The recent studies
      demonstrated that potassium channels were associated with macrophage functions,
      such as activation, migration and cytokines secretion. However, less is known
      regarding the expression and function of ERG channels in AMs. Our study showed
      that ERG1 channel expressed in rat alveolar macrophage, and the expression level
      was increased when AMs were stimulated with LPS. Furthermore, blockade of ERG1
      channels with E4031 down-regulated the mature of ERG1 protein, inhibited NF
      kappaB translocation into the nucleus, and reduced LPS-stimulated IL-6 and IL
      1beta secretion. These results imply that ERG1 channels are functionally
      expressed in rat alveolar macrophages and play an important role in inflammatory
      response.

PMID- 23138561
TI  - Factor XIII and alternatively activated macrophages - new targets in aortic valve
      stenosis.

PMID- 23138562
TI  - Variation patterns in individual fish responses to chemical stress among
      estuaries, seasons and genders: the case of the European flounder (Platichthys
      flesus) in the Bay of Biscay.
AB  - The objective was to describe and model variation patterns in individual fish
      responses to contaminants among estuaries, season and gender. Two hundred twenty
      seven adult European flounders were collected in two seasons (winter and summer)
      in four estuaries along the Bay of Biscay (South West France), focusing on a
      pristine system (the Ster), vs. three estuaries displaying contrasted levels of
      contaminants (the Vilaine, Loire and Gironde). Twenty-three variables were
      measured by fish, considering the load of contaminants (liver metals, liver and
      muscle persistent organic pollutants, muscle polycyclic aromatic hydrocarbons);
      the gene expression (Cyt C oxydase, ATPase, BHMT, Cyt P450 1A1, ferritin); the
      blood genotoxicity (Comet test); and liver histology (foci of cellular alteration
      tumour, steatosis, inflammation, abnormal glycogen storage). Canonical redundancy
      analysis (RDA) was used to model these variables using gender, season and estuary
      of origin as explanatory variables. The results underlined the homogeneity of
      fish responses within the pristine site (Ster) and more important seasonal
      variability within the three contaminated systems. The complete model RDA was
      significant and explained 35 % of total variance. Estuary and season respectively
      explained 30 and 5 % of the total independent variation components, whilst gender
      was not a significant factor. The first axis of the RDA explains nearly 27 % of
      the total variance and mostly represents a gradient of contamination. The links
      between the load of contaminants, the expression of several genes and the
      biomarkers were analysed considering different levels of chemical stress and a
      possible multi-stress, particularly in the Vilaine estuary.

PMID- 23138563
TI  - Contralateral approach to unruptured superior hypophyseal artery aneurysms.
AB  - OBJECTIVE: To evaluate the feasibility and limitations of the contralateral
      approach to unruptured superior hypophyseal artery (SHA) aneurysms. METHODS: Data
      regarding eight cases of superior hypophyseal artery aneurysms operated on by a
      contralateral pterional approach at our center from January 2008 to September
      2010 were collected and evaluated retrospectively. Of these eight cases, six were
      male and two were female. The mean age was 57.1 years (range 28 years to 77
      years). All the aneurysms were unruptured; five were on right side and three were
      on left side. The surgical technique and outcome of patients were reviewed.
      RESULTS: All aneurysms were successfully clipped without complication and patency
      of all superior hypophyseal arteries was preserved. Postoperative three
      dimensional computed tomography angiography revealed residual aneurysm in only
      one case. None of the patients had deterioration of visual acuity or field after
      surgery. The contralateral pterional approach was found to be appropriate for
      fully exposing the aneurysmal dome and neck without retraction of the optic nerve
      or the carotid artery in five cases. Slight retraction of the optic nerve was
      required in two cases, and significant manipulation of the optic nerve was
      required in one case. CONCLUSIONS: The contralateral pterional approach for
      clipping of unruptured superior hypophyseal artery aneurysms is technically
      feasible and safe in a select group of patients where optimal results can be
      achieved without significant retraction of near by neurovascular structures.

PMID- 23138564
TI  - Postoperative extradural hematomas.
AB  - Postoperative extradural hematoma (POEH) is a possible complication after head
      surgery, often neglected in the literature. In a single surgeon experience we
      found 13 cases of POEH (0.8%). We distinguished two subtypes: (1) larger
      hematomas (>40 cc) with typical features and overt clinical picture that always
      needed evacuation, and (2) smaller hematomas (<40 cc) with insidious clinical
      onset and different radiological features compared with traumatic and spontaneous
      extradural hematomas. On the basis of our experience, we propose that clinical
      picture and radiologic appearance lead the decision between conservative or
      interventional treatment of type II hematomas.

PMID- 23138565
TI  - Bringing pharmacogenetics to the bedside.

PMID- 23138566
TI  - The real deal: what judgments of really reveal about how people think about
      artifacts.
AB  - It is widely assumed that artifacts fall into distinct kinds. These kinds are
      generally identified by appeal to words-chair versus stool versus bowl versus
      vase, and so on. But contextual and cross-linguistic variation in what artifacts
      are grouped together by name raise questions about whether artifacts indeed do
      fall into fixed kinds. Can judgments of what artifacts really are reveal a true
      kind membership, distinct from what the objects are called in communicative
      contexts? In two experiments, we examined what drives judgments of what an
      artifact really is and what these judgments can tell us about how people think
      about artifacts. In both experiments, we found that people failed to treat
      artifacts as having a definitive kind membership in their judgments of what the
      artifacts really were. Instead, really judgments reflected the typicality of
      objects with respect to the things normally called by the queried name. If these
      judgments are taken as direct evidence about the existence of artifact kinds, the
      outcome argues against such kinds. Alternatively, really judgments themselves may
      be fundamentally linguistic in nature, and so unable to tap into underlying kind
      memberships. In either case, if such kinds exist, they remain to be found. A more
      likely reality may be that intuitions about the existence of artifact kinds
      reflect the partial clustering of objects in similarity space, plus the fact that
      each language provides names for some constellations of objects in that space.

PMID- 23138567
TI  - Why interleaving enhances inductive learning: the roles of discrimination and
      retrieval.
AB  - Kornell and Bjork (Psychological science 19:585-592, 2008) found that
      interleaving exemplars of different categories enhanced inductive learning of the
      concepts based on those exemplars. They hypothesized that the benefit of mixing
      exemplars from different categories is that doing so highlights differences
      between the categories. Kang and Pashler (Applied cognitive psychology 26:97-103,
      2012) obtained results consistent with this discriminative-contrast hypothesis:
      Interleaving enhanced inductive learning, but temporal spacing, which does not
      highlight category differences, did not. We further tested the discriminative
      contrast hypothesis by examining the effects of interleaving and spacing, as well
      as their combined effects. In three experiments, using photographs of butterflies
      and birds as the stimuli, temporal spacing was harmful when it interrupted the
      juxtaposition of interleaved categories, even when total spacing was held
      constant, supporting the discriminative-contrast hypothesis. Temporal spacing
      also had value, however, when it did not interrupt discrimination processing.

PMID- 23138568
TI  - Connexin 26 facilitates gastrointestinal bacterial infection in vitro.
AB  - Escherichia coli, including enteropathogenic E. coli (EPEC), represents the most
      common cause of diarrhoea worldwide and is therefore a serious public health
      burden. Treatment for gastrointestinal pathogens is hindered by the emergence of
      multiple antibiotic resistance, leading to the requirement for the development of
      new therapies. A variety of mechanisms act in combination to mediate
      gastrointestinal-bacterial-associated diarrhoea development. For example, EPEC
      infection of enterocytes induces attaching and effacing lesion formation and the
      disruption of tight junctions. An alternative enteric pathogen, Shigella
      flexneri, manipulates the expression of Connexin 26 (Cx26), a gap junction
      protein. S. flexneri can open Cx26 hemichannels allowing the release of ATP,
      whereas HeLa cells expressing mutant gap-junction-associated Cx26 are less
      susceptible to cellular invasion by S. flexneri than cells expressing wild-type
      (WT) Cx26. We have investigated further the link between Cx26 expression and
      gastrointestinal infection by using EPEC and S. flexneri as in vitro models of
      infection. In this study, a significant reduction in EPEC adherence was observed
      in cells expressing mutant Cx26 compared with WT Cx26. Furthermore, a significant
      reduction in both cellular invasion by S. flexneri and adherence by EPEC was
      demonstrated in human intestinal cell lines following treatment with Cx26 short
      interfering RNA. These in vitro results suggest that the loss of functional Cx26
      expression provides improved protection against gastrointestinal bacterial
      pathogens. Thus, Cx26 represents a potential therapeutic target for
      gastrointestinal bacterial infection.

PMID- 23138569
TI  - M-cadherin-inhibited phosphorylation of beta-catenin augments differentiation of
      mouse myoblasts.
AB  - beta-Catenin is essential for muscle development because it regulates both
      cadherin-mediated cell-cell adhesion and canonical Wingless and Int1 (Wnt)
      signaling. The phosphorylation of beta-catenin by glycogen synthase kinase-3beta
      (GSK-3beta) at serine31/37/threonine41 regulates its stability and its role in
      canonical Wnt signaling. In this study, we have investigated whether the N
      terminal phosphorylation of beta-catenin is regulated by M-cadherin, and whether
      this regulation mediates the role of M-cadherin in myogenic differentiation. Our
      data show that the knockdown of M-cadherin expression by RNA interference (RNAi)
      in C2C12 myoblasts significantly increases the phosphorylation of beta-catenin at
      Ser33/37/Thr41 and decreases the protein abundance of ser37/thr41
      unphosphorylated active beta-catenin. Furthermore, M-cadherin RNAi promotes
      TCF/LEF transcription activity but also blunts the initiation of the myogenic
      progress by Wnt pathway activator lithium chloride or Wnt-3a treatment. Knockdown
      of beta-catenin expression by RNAi decreases myogenic induction in myoblasts.
      Forced expression of a phosphorylation-resistant beta-catenin plasmid (S33Y-beta
      catenin) fails to enhance myogenic differentiation, but it partially rescues
      C2C12 cells from M-cadherin RNAi-induced apoptosis. These data show, for the
      first time, that M-cadherin-mediated signaling attenuates beta-catenin
      phosphorylation at Ser31/37/Thr41 by GSK-3beta, and that this regulation has a
      positive effect on myogenic differentiation induced by canonical Wnt signaling.

PMID- 23138571
TI  - Ground state depletion microscopy for imaging interactions between gold nanowires
      and fluorophore-labeled ligands.
AB  - Ground state depletion with individual molecule return (GSDIM) is used to
      interrogate the location of individual fluorescence bursts from fluorophore
      labelled DNA molecules on gold nanowire surfaces. Carboxytetramethyl rhodamine
      (TAMRA)-labelled double-stranded DNA molecules were bound to the surface of gold
      nanowires via gold-thiol linkages. Individual fluorescence bursts were spatially
      localized using point spread function fitting and used to reconstruct the image
      of the underlying nanowire. While the reconstructed images reproduce the size and
      shape of the nanowire structures, plasmonic coupling between the nanowire and
      fluorophore is observed, indicating that the location of the observed
      fluorescence may not precisely correlate with the location of the emitting
      fluorophore. Thus, plasmonic coupling is an important factor when using super
      resolution imaging techniques to study plasmonic nanostructures.

PMID- 23138570
TI  - Metabolic preconditioning of mammalian cells: mimetic agents for hypoxia lack
      fidelity in promoting phosphorylation of pyruvate dehydrogenase.
AB  - Induction of HIF-1alpha by oxygen limitation promotes increased phosphorylation
      and catalytic depression of mitochondrial pyruvate dehydrogenase (PDH) and an
      enhanced glycolytic poise in cells. Cobalt chloride and desferrioxamine are
      widely used as mimics for hypoxia because they increase the levels of HIF-1alpha.
      We evaluated the ability of these agents to elicit selected physiological
      responses to hypoxia as a means to metabolically precondition mammalian cells,
      but without the detrimental effects of hypoxia. We show that, while CoCl(2) does
      increase HIF-1alpha in a dose-dependent manner, it unexpectedly and strikingly
      decreases PDH phosphorylation at E1alpha sites 1, 2, and 3 (Ser(293), Ser(300),
      and Ser(232), respectively) in HepG2 cells. This same effect is also observed for
      site 1 in mouse NIH/3T3 fibroblasts and J774 macrophages. CoCl(2) unexpectedly
      decreases the mRNA expression for PDH kinase-2 in HepG2 cells, which likely
      explains the dephosphorylation of PDH observed. And nor does desferrioxamine
      promote the expected increase in PDH phosphorylation. Dimethyloxaloylglycine (a
      prolyl hydroxylase inhibitor) performs better in this regard, but failed to
      promote the stronger effects seen with hypoxia. Consequently, CoCl(2) and
      desferrioxamine are unreliable mimics of hypoxia for physiological events
      downstream of HIF-1alpha stabilization. Our study demonstrates that mimetic
      chemicals must be chosen with caution and evaluated thoroughly if bona fide
      cellular outcomes are to be promoted with fidelity.

PMID- 23138572
TI  - Sensitivities of rat primary sensory afferent nerves to magnesium:  implications
      for differential nerve blocks.
AB  - CONTEXT: Contrasting findings have been published regarding the role of magnesium
      sulphate used as an additive to local anaesthetics in peripheral nerve blocks.
      OBJECTIVE: To clarify the effect of magnesium sulphate on nerve excitability.
      SETTING: C and Abeta compound action potentials were recorded extracellularly in
      vitro in saphenous nerves from adult rats. ANIMALS: Saphenous nerves (n = 30)
      from male Wistar rats (n = 19), 12 to 16 weeks old. INTERVENTION: Primary sensory
      afferents were tested with a computerised threshold tracking program (QTRAC) with
      a supramaximal 1 ms current pulse either alone or after 300 ms of conditioning
      polarising ramp currents in the presence and absence of 10 mmol l magnesium
      sulphate, 80 MUmol l lidocaine and a combination of both. MAIN OUTCOME MEASURES:
      Changes in current thresholds to elicit compound action potential amplitudes of
      40% of the maximal response. RESULTS: Magnesium sulphate increased excitability
      thresholds to a greater extent in Abeta fibres than in C fibres. It enhanced the
      effects of lidocaine in both Abeta fibres [mixture 0.470 mA (SD 0.105) versus
      lidocaine 0.358 mA (SD 0.080), P < 0.001] and C fibres [mixture 2.531 mA (SD
      0.752) versus lidocaine 2.385 mA (SD 0.656), P = 0.008]. Preconditioning
      experiments also showed that magnesium sulphate had an enhancing effect with
      lidocaine in Abeta fibres [mixture 0.620 mA (SD 0.281) versus lidocaine 0.543 mA
      (SD 0.315), P = 0.005], but not in C fibres [mixture 2.412 mA (SD 0.641),
      lidocaine 2.461 mA (SD 0.693), P = 0.17]. CONCLUSION: These results suggest that
      the binding of magnesium ions depends on both the type and conformational state
      of voltage-gated sodium channels. They also may help to explain the conflicting
      reports regarding the clinical effects of magnesium sulphate as an additive to
      lidocaine in peripheral nerve blocks.

PMID- 23138573
TI  - Is previous cholecystectomy a contraindication to paracetamol/codeine
      premedication?

PMID- 23138574
TI  - 3,4-Methylenedioxymethamphetamine induces a hyperthermic and hypermetabolic
      crisis in pigs with and without a genetic disposition for malignant hyperthermia.
AB  - BACKGROUND: Clinical symptoms of acute 3,4-methylenedioxymethamphetamine (MDMA)
      intoxication and malignant hyperthermia have many similarities. At present,
      however, there is contradictory evidence concerning the malignant hyperthermia
      trigger potency of MDMA. OBJECTIVE: This study was designed to investigate
      whether MDMA has malignant hyperthermia trigger potential and leads to malignant
      hyperthermia in pigs with or without a genetic predisposition to the condition.
      In addition, the therapeutic effectiveness of a new dantrolene sodium suspension
      was examined. DESIGN: Experimental study, using an animal model of Pietrain pigs.
      SETTINGS: Institute for Research in Operative Medicine, University of
      Witten/Herdecke, Hospital Cologne Merheim, Cologne, Germany, October 2006 to
      February 2007. Trigger-free anaesthesia was performed on seven malignant
      hyperthermia-susceptible and six malignant hyperthermia-normal Pietrain pigs, and
      cumulative doses of MDMA were administered to each animal. INTERVENTIONS: After
      achieving predefined malignant hyperthermia criteria, standardised therapy was
      initiated; dantrolene sodium suspension (5 mg kg(-1)) was administered and the
      injection was repeated after 24 min. MAIN OUTCOME MEASURES: The malignant
      hyperthermia trigger potency of MDMA was analysed by monitoring pH, PaCO2 and
      temperature. In addition, concentrations of thyroid hormone, mitochondrial
      uncoupling protein 3, noradrenaline and free fatty acids during administration of
      MDMA and dantrolene sodium suspension were analysed. RESULTS: MDMA administration
      led to fulminant hypermetabolic and hyperthermic responses in malignant
      hyperthermia-susceptible and malignant hyperthermia-normal pigs, with significant
      decreases in pH (susceptible: pH 7.21 +/- 0.11, normal: pH 7.21 +/- 0.07), severe
      hypercapnia (susceptible: paCO2 10.3 +/- 3.5 kPa, normal: paCO2 9.8 +/- 1.7 kPa),
      and hyperthermia (susceptible: 40.6 +/- 2.0 degrees C, normal: 40.1 +/- 0.4
      degrees C). There were no significant differences in changes in clinical and
      laboratory variables between groups. The dantrolene therapy regimen was effective
      in treating the MDMA-induced metabolic crises. CONCLUSION: MDMA is not a classic
      trigger for the development of malignant hyperthermia reactions in pigs. MDMA
      intoxication leads to severe, long-lasting hyperthermia and hypermetabolism in
      both malignant hyperthermia-susceptible and hyperthermia-normal pigs, with life
      threatening malignant hyperthermia-like symptoms which are responsive to
      supportive treatment and dantrolene sodium suspension.

PMID- 23138576
TI  - The importance of lag screw position for the stabilization of trochanteric
      fractures with a sliding hip screw: a subject-specific finite element study.
AB  - Using finite element analysis, we compared the biomechanical performance of a CT
      scan-based three-part trochanteric fracture model (31-A2 in the AO
      classification) stabilized with a sliding hip screw for nine different positions
      of the lag screw (3 * 3 arrangement, from anterior to posterior and from inferior
      to superior). Our results showed that the volume of bone susceptible to yielding
      in the head and neck region is the lowest for inferior positions and increases as
      the lag screw is moved superiorly. Overall, for this specific subject, the models
      less likely to lead to cut-out are the ones corresponding to inferior middle and
      inferior posterior positions of the lag screw. In our study, the tip-apex
      distance (TAD) was anti-correlated with the risk of cut-out, as quantified by the
      volume of bone susceptible to yielding, which suggests that a TAD >25 mm cannot
      be considered to be an accurate predictor of lag screw cut-out. Further clinical
      studies investigating lag screw cut-out should attempt to find more reliable
      predictors of cut-out that should better reflect the biomechanics and subject
      specificity of the femoral head.

PMID- 23138575
TI  - Endothelial progenitor cells: the promise of cell-based therapies for acute lung
      injury.
AB  - BACKGROUND: Endothelial progenitor cells (EPCs) are defined as a special type of
      stem cell that have been found to directly incorporate into injured vessels and
      that participate in angiogenesis and reconstruction by differentiation into
      endothelial cells. EPCs are widely used to therapeutically treat cardiovascular
      disease, limb ischemia and vascular repair. However, the role of EPCs in
      inflammatory diseases, especially in lung injury, is less studied. OBJECTIVE: To
      investigate the application of EPCs to vascular repair, and the role of EPCs in
      acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). METHODS:
      A computer-based online search was performed in the PubMed database and Web of
      Science database for articles published, concerning EPCs, angiogenesis, ALI/ARDS
      and stem cell transplantation CONCLUSION: EPCs have a therapeutic potential for
      vascular regeneration and may emerge as novel strategy for the diseases that are
      associated with ALI/ARDS.

PMID- 23138577
TI  - Equity and efficiency: striving for a solution for the introduction of new
      medicines.
AB  - The aim of this study was to describe the evolution of mechanisms to manage the
      introduction of new medicines and their impact on the health-care system in
      Scotland. The study was a review of published and unpublished national audits and
      surveys on the introduction of new medicines in Scotland. Before the Scottish
      Medicines Consortium (SMC) was established, Area Drug and Therapeutics Committees
      (ADTCs) played a key role in advising National Health Service (NHS) Boards in
      Scotland on the use of new medicines. There was evidence of variation in the
      medicines evaluated and, in some cases, the evidence used leading to different
      decisions for the same medicine. After the SMC was established, ADTC decisions
      had become more consistent and comprehensive. The role of ADTCs evolved from
      evaluation of medicines to assessment of local implications and implementation of
      SMC advice. There was increased recognition of the importance of monitoring
      medicine use. This review demonstrated a clear evolution in the evaluation and
      implementation of new medicines by ADTCs across NHS Scotland. After the SMC was
      established, more medicines were considered by ADTCs and there was greater
      consistency in those considered for local implementation. ADTCs have moved from
      evaluation of new medicines to other aspects of medicine management, including
      assessment of local implications and implementation of SMC advice.

PMID- 23138578
TI  - Childhood self-poisoning: a one-year review.
AB  - Self-poisoning in children is a serious health concern accounting for 2% and 5%
      of childhood deaths in the developed and developing world, respectively. Type of
      poison and intent varies between age groups, with alcohol poisoning becoming
      increasingly common in teenagers. The aim of the study was to identify the
      characteristics of paediatric self-poisoning at Ninewells Hospital, Dundee, as a
      function of age, sex, intent and type of poison. Data from patients under the age
      of 17 presenting to Ninewells Hospital's Emergency Department with self-poisoning
      from 1 December 2008 to 30 November 2009 inclusive were identified, classified
      and analysed using chi-square testing. Overall there was no significant
      difference in gender. However, females significantly dominated in the >=12<17
      years age group, with older females also significantly more likely to
      deliberately self-poison. Alcohol was the sole cause of accidental self-poisoning
      in this age group while paracetamol was used in the majority of cases of
      deliberate self-poisoning. In the <6 years age group, household chemical
      ingestion and over-the-counter medications were the most common poisons. The
      findings reflect previous published data and national trends. The prevalence of
      alcohol abuse in the >=12<17 years age group is a major public health issue that
      must be addressed.

PMID- 23138579
TI  - Sacral nerve stimulation for urinary dysfunction: the first year of the Scottish
      national service.
AB  - Sacral nerve stimulation (SNS) has become an established treatment option for
      patients with intractable detrusor overactivity and non-obstructive urinary
      retention. The Scottish Sacral Nerve Stimulation service was established in April
      2010 to provide a service for the population of Scotland. We report our
      experience from the first year of this new national service. All patients
      referred for SNS from the inception of the service in April 2010 until the end of
      March 2011 were studied. During the one-year period, there were 50 referrals.
      Thirty-three percutaneous nerve evaluations, eight tined lead tests and 16
      permanent implantation procedures were performed during this period. Morbidity
      was low and both incontinence and quality-of-life questionnaires demonstrated
      statistically significant improvements (International Consultation on
      Incontinence Questionnaire [ICIQ-SF], P = 0.005; Incontinence Impact
      Questionnaire [IIQ 7], P = 0.0007; Urogenital Distress Inventory [UDI 6], P =
      0.0002). Referral pattern was skewed towards the west of Scotland with some
      health boards producing no referrals during the year. Results from the first year
      of the service have shown that it is a safe and efficient procedure with
      significant improvement in incontinence, voluntary voiding and quality-of-life
      parameters. The limitation of funding for permanent implants inevitably impacts
      on the role of the technique as a management option in these patients.

PMID- 23138580
TI  - Scotland's Knowledge Network: translating knowledge into action to improve
      quality of care.
AB  - The Knowledge Network (www.knowledge.scot.nhs.uk) is Scotland's online knowledge
      service for health and social care. It is designed to support practitioners to
      apply knowledge in frontline delivery of care, helping to translate knowledge
      into better health-care outcomes through safe, effective, person-centred care.
      The Knowledge Network helps to combine the worlds of evidence-based practice and
      quality improvement by providing access to knowledge about the effectiveness of
      clinical interventions ('know-what') and knowledge about how to implement this
      knowledge to support individual patients in working health-care environments
      ('know-how'). An 'evidence and guidance' search enables clinicians to quickly
      access quality-assured evidence and best practice, while point of care and mobile
      solutions provide knowledge in actionable formats to embed in clinical workflow.
      This research-based knowledge is complemented by social networking services and
      improvement tools which support the capture and exchange of knowledge from
      experience, facilitating practice change and systems improvement. In these cases,
      the Knowledge Network supports key components of the knowledge-to-action cycle-
      acquiring, creating, sharing and disseminating knowledge to improve performance
      and innovate. It provides a vehicle for implementing the recommendations of the
      national Knowledge into Action review, which outlines a new national approach to
      embedding knowledge in frontline practice and systems improvement.

PMID- 23138581
TI  - The organization of tissue banking in Scotland.
AB  - Tissue banking in Scotland has developed significantly over the past 20 years or
      so. The range of issues procured has increased and so have their numbers.
      Initially, bone from live donors was the only tissue banked; later, tissues from
      multiorgan donors were procured; this was finally followed by the collection of
      tissues from donors following cardiac death. Bones, tendons, heart valves and
      skin are the main tissue types collected, stored and issued for clinical use.
      Much of our activity is based on identification of donors in two major accident
      and emergency departments followed by retrievals that take place in a dedicated
      mortuary by fully-trained staff. Tissues are released according to clinical need
      for Scottish patients and beyond. All of the tissue banking activity in Scotland
      takes place within the Scottish National Blood Transfusion Service, which is the
      preferred provider of tissues for Scottish patients. There is very close
      cooperation between our teams, the transplant teams and other clinical
      colleagues, including pathologists and anatomical technicians. The achievements
      in issue banking in Scotland are outlined along with the main clinical
      indications of the tissue procured. Diversification is now taking place into
      cellular therapy with the establishment of an islet processing programme and cell
      culturing techniques. The future is very exciting.

PMID- 23138582
TI  - From encephalitis lethargica to cerebral cytoarchitectonics: the polymath talent
      of Constantin von Economo (1876-1931), pioneer neuroanatomist, neurophysiologist
      and military aviator.
AB  - Born in Romania of Greek parents and raised in Trieste, Constantin von Economo
      was educated and influenced by Vienna's medical and scientific tradition. Better
      known for his description of encephalitis lethargica, a disease bearing his name,
      he made several contributions to as varied themes as the cytoarchitecture of the
      cerebral cortex, sleep regulation, evolutionary brain development and, outside
      medicine, in aviation. While still a student he showed an aptitude for meticulous
      accuracy and a skill in combining animal experiments with microanatomical
      techniques. Nurtured in the formidable environment of Viennese histology he
      produced a monumental account of the cytoarchitecture of the human cerebral
      cortex. This, in an attempt to correlate structure and function, was unique in
      its quality of accuracy and paved the way for subsequent achievements two decades
      later. Despite an untimely death at 55 years, he remains one of the most talented
      pioneers of modern neuroscience.

PMID- 23138584
TI  - Impact and workload implications on service provision with establishment of a
      neonatal complex airway service in Scotland.
AB  - The objective of this study was to assess if any changes have occurred in the
      utilization of neonatal services with referral for neonatal airway assessment and
      how this is related to the establishment of a National Complex Airway Service. A
      retrospective case-note review was performed for neonates referred for airway
      assessment from 2004-2010 inclusive. Seventy-nine neonates were referred from
      throughout Scotland; 10 in 2004-2006, 24 in 2007-2008 and 45 in 2009-2010. The
      mean gestational age was 35 weeks; 39% were preterm. Stridor was the most common
      reason for referral (46%). The most common diagnosis was airway malacia (38%).
      Fifty-three procedures were performed on the ward. In total, 64
      microlaryngobronchoscopies were performed; 45 diagnostic and 19 interventional.
      The most common intervention was supraglottoplasty for airway malacia. Thirty
      five separate airway procedures were undertaken. Additional investigations were
      frequently requested and co-morbidities were common. Since the establishment of
      the Scottish National Complex Airway Service in 2006, referrals for neonatal
      airway assessment have increased significantly. The reasons for this include a
      greater awareness of the service, improved treatment options and increased
      preterm survival. These neonates frequently have associated co-morbidities and
      require a repertoire of specialist input. This increase has significant
      implications for further service provision.

PMID- 23138586
TI  - Ventricular assist devices for all?

PMID- 23138585
TI  - Aggregatibacter aphrophilus endocarditis: a case report.
AB  - We present a case of endocarditis with embolic stroke and digital infarction due
      to the recently renamed Aggregatibacter aphrophilus. The isolation and
      identification of this organism can be problematic but was achieved in this case
      using both older phenotypic and newer genotypic methods. A benign tongue lesion
      is suggested as the likely portal of entry for this oropharyngeal organism. The
      patient made a good recovery with six weeks of intravenous ceftriaxone but will
      need cardiac valvular surgery at some point in the future.

PMID- 23138587
TI  - The clinical relevance of antibody-mediated rejection: a new era of heart
      transplantation.

PMID- 23138588
TI  - Coarctation repair mimicking acute aortic dissection.

PMID- 23138591
TI  - Modified 'dumbbell' technique: a simple and intuitive method to position balloon
      expandable stent valves.
AB  - Intraoperative cardiac imaging plays a key role during transcatheter aortic valve
      replacement. In recent years, new techniques and new tools for improved image
      quality and virtual navigation have been proposed, in order to simplify and
      standardize stent valve positioning and implantation. But routine performance of
      the new techniques may require major economic investments or specific knowledge
      and skills and, for this reason, they may not be accessible to the majority of
      cardiac centres involved in transcatheter valve replacement projects.
      Additionally, they still require injections of contrast medium to obtain computed
      images. Therefore, we have developed and describe here a very simple and
      intuitive method of positioning balloon-expandable stent valves, which represents
      the evolution of the 'dumbbell' technique for echocardiography-guided
      transcatheter valve replacement without angiography. This method, based on the
      partial inflation of the balloon catheter during positioning, traps the crimped
      valve in the aortic valve orifice and, consequently, very near to the ideal
      landing zone. It does not require specific echocardiographic knowledge; it does
      not require angiographies that increase the risk of postoperative kidney failure
      in elderly patients, and it can be also performed in centres not equipped with a
      hybrid operating room.

PMID- 23138590
TI  - Optimized temporary bi-ventricular pacing improves haemodynamic function after on
      pump cardiac surgery in patients with severe left ventricular systolic
      dysfunction: a two-centre randomized control trial.
AB  - OBJECTIVES: Optimized temporary bi-ventricular (BiV) pacing may benefit heart
      failure patients after on-pump cardiac surgery compared with conventional dual
      chamber right ventricular (RV) pacing. An improvement in haemodynamic function
      with BiV pacing may reduce the duration of 'Level 3' intensive care. METHODS:
      Thirty-eight patients in sinus rhythm, ejection fraction <=35%, undergoing on
      pump surgical revascularization, valve surgery or both were enrolled in this
      study. Before closing the sternum, temporary epicardial pacing wires were
      attached to the right atrium, RV outflow tract and basal posterolateral wall of
      the left ventricle. Patients were randomly assigned to postoperative BiV pacing
      with the optimization of the atrio- (AV) and inter-ventricular (VV) pacing
      intervals (Group 1) or conventional dual-chamber right AV pacing (Group 2). The
      primary end-point was the duration of 'Level 3' intensive care. Secondary end
      points included cardiac output which was measured by thermodiluation at admission
      to the intensive care unit and at 6 and 18 h later, in five different pacing
      modes. RESULTS: The duration of 'Level 3' care was similar between groups (40 +/-
      35 vs 54 +/- 63 h; Group 1 vs 2; P = 0.43). Cardiac output was similar in all
      pacing modes at baseline. At 18 h, cardiac output with BiV pacing (5.8 l/min) was
      7% higher than atrial inhibited (5.4 l/min) and 9% higher than dual-chamber RV
      pacing (5.3 l/min; P = 0.02 and 0.001, respectively). Optimization of the VV
      interval produced a further 4% increase in cardiac output compared with baseline
      settings (P = 0.005). CONCLUSIONS: Postoperative haemodynamic function may be
      enhanced by temporary BiV pacing of high-risk patients after on-pump cardiac
      surgery.

PMID- 23138592
TI  - Ion-mediated enhancement of xylem hydraulic conductivity in four Acer species:
      relationships with ecological and anatomical features.
AB  - The 'ionic effect', i.e., changes in xylem hydraulic conductivity (k(xyl)) due to
      variation of the ionic sap composition in vessels, was studied in four Acer
      species growing in contrasting environments differing in water availability.
      Hydraulic measurements of the ionic effect were performed together with
      measurements on the sap electrical conductivity, leaf water potential and vessel
      anatomy. The low ionic effect recorded in Acer pseudoplatanus L. and Acer
      campestre L. (15.8 and 14.7%, respectively), which represented two species from
      shady and humid habitats, was associated with a low vessel grouping index, high
      sap electrical conductivity and least negative leaf water potential. Opposite
      traits were found for Acer monspessulanum L. and Acer platanoides L., which
      showed an ionic effect of 23.6 and 23.1%, respectively, and represent species
      adapted to higher irradiance and/or lower water availability. These findings from
      closely related species provide additional support that the ionic effect could
      function as a compensation mechanism for embolism-induced loss of k(xyl), either
      as a result of high evaporative demand or increased risk of hydraulic failure.

PMID- 23138593
TI  - Haloaurate and halopalladate imidazolium salts: structures, properties, and use
      as precursors for catalytic metal nanoparticles.
AB  - The synthesis and characterisation of a series of new gold- and palladium
      containing symmetrical imidazolium salts are described which display significant
      cation-dependent effects determined by the structure of the alkyl chains of the
      imidazolium motifs. Whereas direct reduction of the Pd salts can produce stable
      nanoparticles (NPs) coated by imidazolium salts, the addition of strong base to
      the Pd or Au salts before reduction gives stable NPs, potentially pacified by N
      heterocyclic carbene units. The possibility of NP surface protection by metal
      carbon bonds in these systems is investigated by spectroscopic, synthetic, and
      catalytic investigations, providing support for the hypothesis. Significantly,
      the catalytic activity of the NPs is not inhibited by the continued presence of
      the ligands.

PMID- 23138594
TI  - Role of SbmA in the uptake of peptide nucleic acid (PNA)-peptide conjugates in E.
      coli.
AB  - Antisense PNA oligomers targeting essential genes (acpP or ftsZ) and conjugated
      to the delivery peptide L((KFF)(3)K) show complete growth inhibition of wild type
      E. coli strain (MG1655) with submicromolar MIC. In this study we show that
      resistant mutants generated against such PNA-peptide conjugates had disruptions
      in the region of sbmA, a gene encoding an inner membrane peptide transporter. The
      wild type sensitivity to the PNA conjugates was re-established in the resistance
      mutants by complementation with sbmA. Furthermore, deletion of sbmA in E. coli
      AS19, a strain that is sensitive to unmodified PNA, resulted in resistance to
      PNA. Finally, PNA conjugated with the corresponding non-biological H-D((KFF)(3)K)
      peptide retained antibacterial activity in sbmA deletion strains, whereas the
      same conjugate with a protease-sensitive linker did not. These results clearly
      identify SbmA as a carrier of naked PNA over the inner bacterial membrane and
      thereby infer that the peptide is transporting the PNA conjugates over the outer
      membrane. Strains lacking SbmA were used to screen novel peptide-PNA carriers
      that were SbmA-independent. Four such PNA-peptide conjugates, H-D((KFF)(3)K), H
      (RFR)(4)-Ahx-betaAla, H-(R-Ahx-R)(4)-Ahx-betaAla, and H-(R-Ahx)(6)-betaAla, were
      identified that utilize an alternative uptake mechanism but retain their
      antimicrobial potency. In addition SbmA is the first protein identified to
      recognize PNA.

PMID- 23138595
TI  - C60-mediated hydrogen desorption in Li-N-H systems.
AB  - Hydrogen desorption from a LiH + NH(3) mixture is very difficult due to the
      formation of the stable LiNH(4) compound. Using cluster models and first
      principles theory, we demonstrate that the C(60) molecule can in fact
      significantly improve the thermodynamics of ammonia-mediated hydrogen desorption
      from LiH due to the stabilization of the intermediate state, LiNH(4). The
      hydrogen desorption following the path of LiNH(4)-C(60) -> LiNH(3)-C(60) +
      1/2H(2) is exothermic. Molecular dynamic simulations show that this reaction can
      take place even at room temperature (300 K). In contrast, the stable LiNH(4)
      compound cannot desorb hydrogen at room temperature in the absence of C(60). The
      introduction of C(60) also helps to restrain the NH(3) gas which is poisonous in
      proton exchange membrane fuel cell applications.

PMID- 23138596
TI  - Chemopreventive effects of selenium on cancer marker indices and ultrastructural
      changes during 1,2 dimethylhydrazine-induced colon carcinogenesis in rats.
AB  - PURPOSE: The present study was conducted to elucidate the potential of selenium
      supplementation, if any, in affording chemoprevention by modulating the altered
      cancer markers and ultrastructural changes in dimethyl hydrazine (DMH)-induced
      colorectal carcinogenesis in rats. METHODS: The rats were segregated into four
      groups, viz., normal control, DMH treated, selenium treated, and DMH + selenium
      treated. Initiation and induction of colon carcinogenesis was achieved through
      weekly subcutaneous injections of DMH (30 mg/kg body weight) for both 10 and 20
      weeks. Selenium was supplemented to rats at a dose level of 1 ppm in drinking
      water ad libitum for two different time durations of 10 and 20 weeks. RESULTS:
      The study observed a significant increase in the number of aberrant crypt foci
      (ACF) in colons of DMH-treated rats at both time intervals which were decreased
      significantly upon selenium supplementation. Also, a significant increase was
      seen in the enzyme activity of alkaline phosphatase (ALP), which, however, was
      moderated upon selenium administration to DMH-treated rats. Changes in the
      ultrastructural architecture of colonic cells were apparent following both the
      treatment schedules of DMH; however, the changes were prominent following 20
      weeks of DMH treatment. The most obvious changes were seen in the form of altered
      nuclear shape and disruption of cellular integrity, which, upon selenium
      supplementation, were appreciably improved. CONCLUSION: In conclusion, the study
      shows the chemopreventive abilities of selenium against DMH-induced colorectal
      carcinogenesis in rats.

PMID- 23138599
TI  - Novel chimney-graft technique for preserving hypogastric flow in complex
      aortoiliac aneurysms.
AB  - We describe the feasibility and result of a novel approach to preserve pelvic
      perfusion during endovascular aortoiliac aneurysm repair (EVAR) in patients with
      aortoiliac aneurysms extending to the iliac bifurcation. The iliac chimney-graft
      technique consists of the deployment of a ViaBahnTM graft into the hypogastric
      artery in combination with standard abdominal aortic stent-grafts. The chimney
      graft was deployed using a transsubclavian access and placed parallel with the
      iliac limb into the standard aortic stent graft, which was deployed directly
      before. The technical procedure was successful. Postoperative control showed a
      sufficiently excluded aneurysm without evidence of endoleak and good distal
      perfusion of both iliac arteries. The CT-scan after 6 months confirmed the
      result. The chimney-graft stent grafts to maintain perfusion to hypogastric
      arteries are feasible and provide an alternative to hypogastric artery exclusion
      or branched grafts. Long-term follow-up is needed to evaluate stent-graft patency
      and failure rates.

PMID- 23138597
TI  - Surgical management of colorectal peritoneal metastases: treatment and outcomes
      compared with hepatic metastases.
AB  - PURPOSE: The liver and peritoneum are common sites of colorectal metastases.
      Hepatectomy for colorectal liver metastases (CLM) is considered gold standard
      treatment. We attempt to compare the survival outcomes for CLM patients after
      hepatectomy to that of patients with colorectal peritoneal metastases (CPM) who
      underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal
      chemotherapy (HIPEC). METHODS: A retrospective review of patients with CPM and
      CLM who underwent surgery between January 2003 and May 2011 was performed. The
      overall (OS) and disease-free survivals (DFS) were compared. RESULTS: There were
      22 patients with CPM who underwent CRS and HIPEC and 186 patients who underwent
      hepatectomy for CLM. Patients with CPM had a 3-year OS of 39 % and DFS of 27.7 %.
      CLM patients showed a 3-year OS of 58.5 % and a DFS of 28.8 %. Most recurrences
      for CPM occurred within 2 years, while CLM patients continue to develop systemic
      recurrences over 3 years, showing a gradual decline in DFS and OS during this
      period of time. CONCLUSION: Our results show that CRS and HIPEC for CPM confer
      good OS and DFS rates and that the DFS after CRS and HIPEC is comparable to that
      after hepatectomy for CLM.

PMID- 23138600
TI  - Single-center experience of percutaneous abdominal aortic aneurysm repair with
      local anesthesia and conscious sedation: technique and results.
AB  - AIM: Totally percutaneous endovascular abdominal aortic aneurysm repair (PEVAR)
      by using the "Preclose" technique has been previously described. We
      retrospectively analyzed data, collected prospectively at our institution,
      regarding PEVAR via femoral artery access with local anesthesia and conscious
      sedation. METHODS: Between January 2001 and May 2009, 1150 patients underwent
      PEVAR in the endovascular suite of the cardiac catheterization laboratory at our
      institution. Of those procedures, 915 (79%) were performed with local anesthesia
      and conscious sedation. RESULTS: The majority of patients were male (87%). Their
      mean age was 72+/-10 years, and 98% had a risk status of American Society of
      Anesthesiologists class III or IV. The PEVAR involved bilateral percutaneous
      femoral access with 12F to 24F sheaths (depending on the stent-graft system). The
      mean total procedure time was 149 minutes. Percutaneous closure of the arterial
      access sites with the Prostar XL was successful in 1727 (94.3%) of the 1830
      femoral arteries in which PEVAR was attempted, whereas 103 femoral arteries
      (5.6%) required surgical repair because adequate hemostasis was not attained at
      the access site. There were no procedural deaths, but 6 patients (0.6%) died
      within 30 days of the procedure: 3 died of intestinal ischemia, 1 of stroke, 1 of
      refractory ventricular arrhythmia, and 1 of worsening renal failure. Mean length
      of hospital stay was 1.3+/-2 days. CONCLUSION: PEVAR with local anesthesia and
      intravenous sedation is safe and feasible and should be considered for patients
      for whom general anesthesia poses a high risk.

PMID- 23138601
TI  - Reinterventions following endovascular abdominal aortic aneurysm repair: the
      learning curve of time.
AB  - AIM: The DREAM and EVAR-1 trial show a higher reintervention rate after
      endovascular aneurysm repair (EVAR) compared to open repair. Since the initiation
      of these trials, endovascular-graft design and the experiences with EVAR have
      evolved substantially. The aim of this study was to compare the need for
      reinterventions in our recent EVAR procedures with our early procedures. METHODS:
      A retrospective review of our prospectively maintained database of all patients
      undergoing an elective EVAR for infrarenal abdominal aortic aneurysm (AAA) was
      performed. The 68 patients treated between 2000 and 2006 were defined as the
      "Early EVAR" group; the 41 patients treated between 2006 and 2008 were defined as
      the "Recent EVAR" group. The median follow-up was 63.3 (range 2-111) and 43.7
      (range 1-61) months in the Early and Recent EVAR group respectively. RESULTS:
      Treatment related mortality occurred in three (4.4%) patients in the Early EVAR
      group. No treatment related mortality occurred in the Recent EVAR group. In the
      Early EVAR group 16 reinterventions occurred in 13 patients (19.1%) and in the
      Recent EVAR group three reinterventions occurred in three patients (7.5%). This
      difference was statistically significant (P=0.039). CONCLUSION: In our center,
      continued experiences with EVAR, improvement of graft design and a different
      management of complications have led to a significant decrease in reinterventions
      after EVAR. These findings and a review of the literature suggests that current
      need for reintervention after EVAR is substantially less than reported in the
      early trials.

PMID- 23138602
TI  - Surgical treatment of infected aortic grafts.
AB  - An infection of an aortic prosthesis is a severe condition with high morbidity
      and mortality rates. Surgical treatment of an infected aortic graft or infected
      aortic stent-graft focuses on treatment of the infection and maintaining or
      restoring perfusion of the lower limbs. Over the years various reconstruction
      options have been introduced, each claiming to be the most successful in securing
      lower limb perfusion. Consensus about the optimum treatment strategy is lacking.
      The frail patient population and the relative rarity of the disease limits
      research on this topic which is an important reason for this lack of consensus.
      In order to determine which of the various treatment options is the most suitable
      to treat aortic graft infections, this systematic review was conducted of the
      available literature of the last 20 years. The search strategy and data
      collection were based on the guidelines of the Meta-analysis Of Observational
      Studies in Epidemiology (MOOSE). Appropriate inclusion and exclusion criteria
      were defined. A total of 862 possibly relevant papers were identified. After
      applying the in- and exclusion, data on mortality, morbidity and complications
      were extracted from a total of 93 papers. This review covers the various surgical
      treatment options available in the treatment of infected aortic (stent) grafts.
      Strategies concerning graft excision are discussed as are the advantages and
      disadvantages of the extra-anatomic reconstruction and its counterpart, the in
      situ reconstruction (using antibiotic-impregnated grafts, autologous vein grafts,
      fresh or cryopreserved allografts, and silver impregnated grafts). Available
      evidence was summarized and used to construct a clinical decision flowchart. All
      reconstruction options seem to have their pros and cons, and all have their use
      in specific situations. The treatment of infected aortic grafts must therefore be
      tailor-made.

PMID- 23138604
TI  - Outcome of extensive descending aorta repair adopting present concepts of spinal
      cord preservatio.
AB  - AIM: Preoperative radiological identification of the Adamkiewicz artery and
      intraoperative neurologic monitoring are known to be helpful for preventing
      paraplegia after thoracoabdominal aorta replacement. To answer whether they
      should be used routinely, we investigated the incidence of spinal cord ischemia
      after extensive descending aortic repair without using such modalities. METHODS:
      We retrospectively reviewed the outcome of 95 patients who underwent extensive
      descending thoracic (DTA) or thoracoabdominal aorta (TAA) repair without the
      Adamkiewicz artery identification or neurologic monitoring from 2006 through
      2010. Spinal cord protection strategy consisted of distal aortic perfusion,
      cerebrospinal fluid drainage, mild hypothermia, and maintenance of hypertension
      (systolic>=120mmHg) through the second postoperative day. A few segmental
      arteries were empirically selected for reimplantation based on the size and the
      amount of backbleeding; overall 1.4 per patient, 0.3 for DTA, 1.4 for type I, 2.4
      for type II, 0.9 for type III, and 0 for type IV TAA. RESULTS: Two patients died
      early after surgery. All the remaining patients awoke without paraplegia or
      paraparesis. Delayed deficit occurred in 7 patients (7.4%) after hypotensive
      events caused by sedation, bleeding, respiratory distress, or cardiac
      dysfunction. Three patients (3.2%) became permanently paraplegic and the other
      four recovered completely within 48 hours after cerebrospinal fluid drainage and
      elevation of systemic blood pressure. CONCLUSION: Even without the Adamkiewicz
      artery identification and neuromonitoring, the incidence of immediate paraplegia
      could be kept low by applying the strategy based on the modern concept of cord
      perfusion. The relatively high incidence of delayed deficit suggests the
      importance of postoperative hemodynamic management and prevention of
      cardiopulmonary complications.

PMID- 23138605
TI  - Fate of aorta and clinical outcomes in patients with chronic type B aortic
      dissection: over 20-year experience.
AB  - AIM: In type B double-barrel aortic dissection (AD), the fate of the affected
      aorta, causes of death, and very long-term clinical outcomes have not been
      completely elucidated. The purpose of this study was to clarify the fate of the
      affected aorta and long-term clinical outcomes in patients with type B AD during
      the chronic phase. MEHODS: One hundred and four patients were entered into this
      study, and regular follow-up CT studies (mean; 87.6 months) were performed. Also,
      clinical data including AD-related events (including aneurysm formation, rupture,
      ischemia, and re-dissection), AD-related deaths, and long-term survival were
      retrospectively reviewed. RESULTS: Forty-six of 104 patients (44.2%) had one more
      AD-related event during the follow-up period. The actuarial event-free rates for
      any AD-related events of all patients were 95+/-2%, 75+/-5%, 53+/-6%, and 13+/-7%
      at 1, 5, 10, and 20 years, respectively. Initial aortic diameter >=40 mm and
      blood flow in the false lumen were significant risk factors for AD-related events
      in univariate and multivariate analysis. CONCLUSION: In type B chronic aortic
      dissection, the affected aortas have a high incidence of AD-related events during
      the follow-up period. Prophylactic surgery or endovascular treatment for patients
      at high risk may reduce the AD-related events.

PMID- 23138606
TI  - Mitral valve repair for the treatment of degenerative mitral valve disease with
      or without prosthetic ring annuloplasty: long-term outcomes.
AB  - AIM: Aim of the study was to evaluate late outcomes of mitral valve repair with
      and without the use of prosthetic ring annuloplasty and standardized techniques
      for the treatment of degenerative mitral regurgitation (MR). METHODS: Three
      hundred and five patients (mean age 62 +/- 12 years) underwent mitral valve
      repair between January 1992 and February 2010 for degenerative MR. In the last
      five years, all repair techniques were performed routinely using prosthetic ring
      annuloplasty, with or without quadrangular or triangular resection of posterior
      leaflet and/or edge-to-edge technique. Mean follow-up (99% complete) was 78 +/-
      46 (2-220) months. RESULTS: Operative mortality was 0.9% (3/305), 15-year
      actuarial survival 82% +/- 4%. At 15 years freedom from cardiac death was 89% +/-
      3.7%, from reoperation 84% +/- 5.8%, from endocarditis 100%. Independent
      predictors of all-causes mortality were advanced age at operation (P=0.0006) and
      mitral valve repair without reductive prosthetic annuloplasty (P=0.0019). Death
      for cardiac causes was significantly higher when reductive annuloplasty was
      performed without the use of prosthetic ring (P<0.01). Late progression to
      moderate or severe MR was observed in 23/299 patients (7.7%). Independent
      predictors of progression to moderate or severe MR was annuloplasty without the
      use of prosthetic ring (P=0.0053) and postoperative residual mild MR (P=0.0014).
      Reoperation was required in 13/299 patients (4.4%). At 10 years freedom from
      moderate or severe MR was 86% +/- 6% and 92% +/- 4% in patients with
      postoperative absent or trivial residual MR, respectively, as compared to 38% +/-
      15% in those with postoperative residual mild MR (P<0.0001), freedom from
      reoperation 94% +/- 4% and 90% +/- 14% vs. 56% +/- 16% (P<0.0001). CONCLUSION:
      Prosthetic annuloplasty in association with standardized techniques confers over
      10 years survival advantage and better durability.

PMID- 23138607
TI  - Management of bicuspid aortic valve with or without involvement of ascending
      aorta and aortic root.
AB  - Patients with a bicuspid aortic valve (BAV) constitute a heterogeneous population
      with variable clinical presentation and complications. More than 50% of the
      patients who require aortic valve replacement have a BAV, a condition that may be
      associated with dilation of ascending aorta and aortic insufficiency caused by
      cusp disease or aortic root pathology. Of the potential BAV-related
      complications, dilation of the aortic root and ascending aorta are among the most
      serious. The dilation of ascending aorta and aortic root have been the subject of
      controversy. Whereas some surgeons believe that the dilation of the aorta is
      caused by the hemodynamic properties of the BAV, others believe that the dilation
      of the aortic root is secondary to genetic defects associated with the BAV.
      Management of a BAV should be tailored to each patient's clinical condition. The
      surgical approach varies from aortic valve replacement to combined aortic valve
      and root replacement to aortic-valve-sparing root replacement. 

PMID- 23138608
TI  - Results of surgical repair of carotid in-stent restenosis.
AB  - AIM: Carotid artery angioplasty and stenting (CAS) has emerged as an alternative
      treatment for extra cranial carotid artery stenosis in stroke prevention.
      Nevertheless concerns are remaining about the long-term durability as hemodynamic
      in-stent restenosis (ISR) after CAS are increasing and usually treated again by
      endovascular approach. This preliminary study, instead, albeit in a limited
      series, reports our safe and successful experience of the surgical correction of
      carotid ISR after CAS. METHODS: From January 2003 to June 2011 seven patients
      with severe hemodynamic carotid ISR (three symptomatic, four asymptomatic, mean
      age 76+/-2), were submitted to surgical operation to remove the carotid stent.
      The indications for CAS were primary in five cases, secondary to restenosis after
      carotid endarterectomy (CEA) in two patients. Standard CEA with complete removal
      of the stent and the entire atherosclerotic plaque was carried out easy and
      without technical difficulty in the five primary ISR. In the two patients of ISR
      in post-CEA restenosis, a common carotid to the distal internal carotid artery
      (ICA) bypass with polytetrafluoroethylene (PTFE) graft was carried out. Mean
      operation time was 88+/-26 min. All interventions were performed under general
      anesthesia with remifentanil preserved consciousness. RESULTS: No death or major
      complications occurred. Temporary vocal cord impairment by deficit of recurrent
      inferior laryngeal nerve in one patient with ISR after CAS performed to treat
      post-CEA restenosis was observed. Intimal hyperplasia was the predominant
      mechanism to ISR. The mean follow-up of 18 months (range, 4 to 36 months) showed
      a normal patency of the surgical correction without recurrent restenosis on color
      coded duplex ultrasounds (US) examinations. CONCLUSION: The surgical management
      of carotid ISR appears feasible and effective leading to good long-term outcome.

PMID- 23138609
TI  - High versus standard clopidogrel loading in patients undergoing carotid artery
      stenting prior to cardiac surgery to assess the number of microemboli detected
      with transcranial Doppler: results of the randomized IMPACT trial.
AB  - AIM: The aim of this study was to compare the effects of 300 mg or 600 mg
      clopidogrel loading dose, prior to carotid artery stenting (CAS) on the number of
      transcranial Doppler (TCD)-detected microembolic signals (MES) and to investigate
      the relationship between the magnitude of platelet reactivity and MES. METHODS:
      In this prospective randomized, double-blind study, 35 consecutive asymptomatic
      patients (17.1% females), scheduled for CAS and cardiac surgery were included.
      The primary endpoint was the number of TCD-detected MES. The secondary endpoints
      were the absolute magnitude of on-treatment platelet reactivity and the adverse
      cerebral events. Negative binomial regression to find predictors for sum of
      single emboli, the student's t-test to assess the association between platelet
      function tests and randomized dose of 300 mg or 600 mg clopidogrel, and the R2
      calculation for the assessment of the association between platelet function tests
      and embolic load, were used. RESULTS: No statistically significant difference in
      the number of TCD-detected MES, in the sum of all the single emboli or showers
      and platelet aggregation measurements between the two groups was observed
      (aggregometry: 21.7+/-18.3 versus 23+/-18%, P=0.8499 and 45.8+/-17.5 versus
      46.5+/-14.5%, P=0.9003) (verifyNow P2Y12 assay: 231+/-93 PRU versus 222+/-86 PRU,
      P=0.7704). In one patient a transient ischemic attack occurred. CONCLUSION: A
      loading dose of 300 mg of clopidogrel in combination with aspirin is as effective
      as 600 mg of clopidogrel in achieving adequate platelet inhibition and preventing
      periprocedural events in asymptomatic patients undergoing CAS prior to cardiac
      surgery.

PMID- 23138610
TI  - Excimer laser atherectomy after unsuccessful angioplasty of TASC C and D lesions
      in femoropopliteal arteries.
AB  - AIM: The study objective was to examine the application of excimer laser
      atherectomy (ELA) in patients with refractory occlusions in femoropopliteal
      arteries, where the initial conventional percutaneous transluminal angioplasty
      (PTA) recanalization attempts, were unsuccessful. METHODS: The average age of the
      40 patients (32 men, 8 women) included in this study was 65.4+/-9.1 years. The
      average occlusion length was 17.5 cm (range: 12-25 cm). The initial
      recanalization attempts were performed with stiff Terumo guidewires (curved or
      straight) supported by various catheters (straight/multipurpose/Cobra). After the
      unsuccessful attempt, an excimer laser catheter (catheter diameters from 1.7-2.5
      mm) was used for recanalization using the step-by-step method of crossing. After
      successful crossing, balloon dilatation was performed in all cases. Stent implant
      was required in 10% (4/40) of procedures. Patients were followed for 12 months
      with colour-coded Duplex sonography (CCDS). RESULTS: The initial technical
      success rate of 90% (36/40) resulted in primary, primary-assisted and secondary
      assisted patency rates of 58.9%, 67.8% and 83.2%, respectively, after 12 months.
      No serious complications occurred that were attributable to the intervention.
      CONCLUSION: According to these results, ELA recanalization provides a low stent
      rate alternative to surgical procedures for refractory occlusions. This would
      offer patients, with increased operative risks, a promising and low-risk
      therapeutic procedure. The option of a subsequent vascular operation would not be
      compromised.

PMID- 23138612
TI  - Photoluminescence of silicon quantum dots in nanospheres.
AB  - Si quantum dots (SiQDs) based nanospheres (SiNSs) were prepared via a novel
      synthetic strategy. These SiNSs were demonstrated to possess unique dot spacing
      dependent photoluminescence (PL) up-conversion and surface dependent (N modified
      surface) down-converted PL. It was demonstrated that a small distance between
      SiQDs (<5 nm) is the necessary condition for the PL up-conversion of SiNSs, while
      the surface state of SiQDs will affect the maximum emission wavelength and the PL
      intensity. The as-prepared SiNSs feature excellent aqueous dispersibility, and
      their optical properties were found to be stable enough in a specified
      temperature and pH range.

PMID- 23138613
TI  - Clinical and histological prognostic factors for local recurrence and metastasis
      of cutaneous squamous cell carcinoma: analysis of a defined population.
AB  - Cutaneous squamous cell carcinomas (cSCC) can recur locally and can metastasize.
      The objective of this study was to identify clinical and histopathological
      prognostic factors for local recurrence and metastasis in cSCCs at any body site.
      Clinical and histopathological data were collected from 224 patients with cSCC.
      During the median follow-up period of 43 months (range 0-73 months) the
      cumulative probabilities of recurrence-free survival at 1, 2 and 4 years post
      treatment were 98.0%, 96.9% and 94.7%, respectively, and for metastasis-free
      survival 98.1%, 97.0% and 95.9%, respectively. In univariate survival analyses,
      predictors for local recurrence were every millimetre increase in tumour diameter
      and in tumour thickness. Predictors for metastasis this was location on the ear,
      invasion of deeper structures, no surgical treatment, poor differentiation, every
      millimetre increase in tumour diameter and in tumour thickness. In multivariate
      survival analysis, every millimetre increase in both tumour diameter and tumour
      thickness were independent predictors for local recurrence as well as for
      metastasis and, therefore, it is important to report these in patients' files.
      Defining prognostic valuables is important for diagnostic work-up, treatment and
      follow-up for an individual patient. 

PMID- 23138614
TI  - Do anti-TNF-alpha drugs increase cancer risk in rheumatoid arthritis patients?
AB  - Concern has been raised about an increased risk of lymphoma and skin cancers in
      patients with rheumatoid arthritis due to administration of anti-TNF-alpha drugs.
      Meta-analysis of observational data from registries as well as from randomized
      controlled trials has failed to show a significant increase in the risk of
      lymphoma when the sample size has been sufficiently large; skin cancer risk may
      represent a valid concern. Issues relating to interpretation of these data are
      discussed.

PMID- 23138616
TI  - [Special issue on staging and profiling: reform of diagnostics].

PMID- 23138615
TI  - Suboptimal iron status and associated dietary patterns and practices in
      premenopausal women living in Auckland, New Zealand.
AB  - PURPOSE: To investigate associations between dietary patterns and suboptimal iron
      status in premenopausal women living in Auckland, New Zealand. METHODS:
      Premenopausal women (n = 375; 18-44 years) were included in this cross-sectional
      analysis. Suboptimal iron status was defined as serum ferritin <20 MUg/L.
      Participants completed a 144-item iron food frequency questionnaire (FeFFQ) and a
      questionnaire on dietary practices to assess dietary intake over the past month.
      Factor analysis was used to determine dietary patterns from the FeFFQ. Logistic
      regression was used to determine associations between these dietary patterns and
      iron status. RESULTS: Seven dietary patterns were identified: refined
      carbohydrate and fat; Asian; healthy snacks; meat and vegetable; high tea and
      coffee; bread and crackers; and milk and yoghurt. Logistic regression suggested
      that following a "meat and vegetable" dietary pattern reduced the risk of
      suboptimal iron status by 41 % (95 % CI: 18, 58 %; P = 0.002) and following a
      "milk and yoghurt" pattern increased the risk of suboptimal iron status by 50 %
      (95 % CI: 15, 96 %; P = 0.003). CONCLUSIONS: These results suggest that dietary
      patterns characterized by either a low intake of meat and vegetables or a high
      intake of milk and yoghurt are associated with an increased risk of suboptimal
      iron status. Dietary pattern analysis is a novel and potentially powerful tool
      for investigating the relationship between diet and iron status.

PMID- 23138617
TI  - [Staging and profiling of psychiatric disorders].
AB  - BACKGROUND: Diagnostic issues are at the heart of medicine. Although the existing
      systems to classify mental disorders have been of tremendous value to Psychiatry,
      there is growing pressure to reform psychiatric diagnosis. In other areas in
      medicine staging and profiling has been a fruitful strategy to model the
      diagnosis of complex disorders. AIM: To examine whether staging and profiling may
      be a fruitful model for the diagnosis of psychiatric disorders. RESULTS: Clinical
      staging and profiling may help to reform our current static, descriptive and
      largely categorical classification of mental disorders and arrive at a diagnostic
      system that is developmental, that can accommodate better the continuous nature
      of most mental health problems and that is sensitive to etiologic and prognostic
      risk factors. CONCLUSION: Looking beyond the forthcoming revisions of DSM and
      ICD, clinical staging and profiling provide the necessary framework for a more
      fundamental reform of psychiatric diagnosis.

PMID- 23138618
TI  - [Disease profiling in haemato-oncology].
AB  - BACKGROUND: In the field of haemato-oncology the staging of disease began in the
      1960s with the mapping of the extent of a disease in order to create
      opportunities for effective local treatment. This led to the characterisation of
      cancer cells with the help of various techniques ranging from microscopy to the
      profiling of gene expression. AIM: To provide an overview of staging and
      profiling in haematology. METHOD: A description is given of the relevant methods
      and techniques and of the way in which these procedures are organised in the
      Netherlands. RESULTS: In haematology it is essential to characterise an illness
      during diagnosis and during treatment. Slowly but surely protocols for estimating
      the severity of the patient's disease and patient's quality of life are being
      introduced. In the Netherlands the Dutch-Belgian Study Group for haemato-oncology
      for adults HOVON foundation) has been actively engaged for 25 years in
      integrating into one structure and one quality system the developments in disease
      profiling and the simultaneous improvements in treatment. CONCLUSION: In the
      treatment of patients with a haematological malignancy it has become normal
      practice to characterise both the diseased cell and the extent of the illness
      during diagnosis and in the course of treatment. Improvements in characterisation
      and in treatment run parallel to each other and influence each other
      continuously. The HOVON foundation keeps a record of the results of each patient.

PMID- 23138619
TI  - [Psychotic disorders: the need for staging].
AB  - BACKGROUND: In psychotic disorders it is the stage of development of the disease
      which mainly determines the prognosis and the effectiveness of treatment. AIM: To
      describe and to refine the current staging and profiling of psychotic disorders
      and to propose a way in which to describe the course of dimensions of psychoses.
      METHOD: We searched the literature for articles relating to the staging of
      psychotic disorders. RESULTS: McGorry e.a. developed a simple classification into
      stages which is currently applicable to research and clinical practice. We
      propose a further refinement in the form of a graph from which one can see in a
      glance the history of clinically relevant variation. CONCLUSION: Research into
      the prodromal stages of diseases is needed in order to elucidate the
      pathophysiological mechanisms that the stages have in common and to reveal the
      pathways of differential development.

PMID- 23138620
TI  - [The characterisation of anxiety disorders: staging and profiling based on common
      sense].
AB  - BACKGROUND: Clinicians need to be well informed about staging and profiling so
      that they can divide patients with anxiety disorders into groups according to the
      phase and severity of their illness. The group to which the patient is assigned
      determines the types of treatment he or she receives. AIM: To investigate ways in
      which clinicians can be helped to apply staging and profiling procedures to
      patients with anxiety disorders. METHOD: We searched the literature for articles
      about the staging and profiling of anxiety disorders. RESULTS: There seems to be
      practically no literature relating to the staging and profiling of anxiety
      disorders. However, in daily practice clinicians do attempt to classify their
      patients and use forms of staging when deciding on special types of treatment for
      their patients and when assessing the length of treatment required. The revised
      Dutch guidelines on anxiety disorders include a generalised form of staging,
      called 'stepped care&rsquo;. These revisions have been made on the basis of
      consensus decisions reached by the guideline committee. CONCLUSION: The revised
      guidelines on anxiety disorders assist clinicians with the application of staging
      in their daily practice. However, because of the lack of scientific data, our
      article closes with the presentation of a research agenda.

PMID- 23138621
TI  - [Staging and profiling in addication].
AB  - BACKGROUND: The existence or non-existence of the formal diagnosis 'substance' or
      'dependence' is in fact of little consequence in terms of the severity of the
      affliction, the course of the disorder and the response to a specific type of
      treatment. Furthermore, the effective treatments that are currently available
      seem to work only in a minority of the patients in routine clinical practice. A
      possible reason for these discrepancies is too much heterogeneity within the
      diagnostic categories. The planned merging of the diagnoses 'substance abuse' and
      'dependence' into a single diagnostic category 'substance use disorder' in DSM-5
      is likely to increase the heterogeneity still further. AIM: To provide
      suggestions for improvement of diagnosis and treatment through staging and
      profiling of addiction and dependency. METHOD: Study of the relevant literature.
      RESULTS: A possible solution is to reduce the heterogeneity by the introduction
      of staging and profiling. Therefore, we present a model for addiction which is
      based on existing models in oncology and on current knowledge about the
      neurobiology of addiction. In addition, we demonstrate in what way individual
      patients with an addiction can be characterised and profiled in more detail
      through the use of phenotypical, endophenotypical and genetic information.
      CONCLUSION: The combination of diagnosis, staging and profiling will lead to more
      effective and efficient treatment for patients suffering from addiction.

PMID- 23138622
TI  - [Staging and profiling in bipolar disorders].
AB  - BACKGROUND: Bipolar disorders are expressed in a wide variety of forms and last
      for different lengths of time. This has a major influence on diagnosis and
      treatment and on the interpretation of research findings. AIM: To propose and
      describe a method for staging and profiling of bipolar disorders. METHOD: We
      searched the literature for evidence of attempts to define stages of illness
      progression and risk factors that determine the course of illness. RESULTS: The
      staging of bipolar disorders evolves from a symptom-free phase with high-risk
      conditions to a treatment-resistent chronic mood disorder. A family history of
      recurrent mood disorder, affective symptoms in childhood and depression in
      adolescence strongly predict future bipolar disorder. The profiling system that
      we propose incorporates not only clinical phenomenology in accordance with
      current classification but also clinically relevant predictors for an unfavorable
      course of illness. These predictors include age at onset, cognitive profiles,
      comorbidity, traumatic life events, psychosis, suicidality, insight into illness,
      and respons to treatment. There is some emerging evidence for genetic or other
      biological markers. CONCLUSION: Staging and profiling may contribute to early
      diagnosis, preventive strategies, and personalised treatment and may provide
      guidance for further research.

PMID- 23138623
TI  - [Staging and profiling of unipolar depression].
AB  - BACKGROUND: Not only is the heterogeneous concept of depression too
      comprehensive, it is also insufficiently differentiated. This serves as a barrier
      to scientific research and obscures the symptoms that should indicate what
      treatment is required. AIM: To describe an accurate model for staging and
      profiling depression. METHOD: We placed depressive disorders in the context of
      the entire course of the disorder and we regarded the course as a continuum of
      psychopathology. RESULTS: First of all we distinguish five stages: (1) the
      prodromal phase, (2) the first depressive episode, (3) residual symptoms
      following an episode, (4) the relapse episode and (5) the chronic and/or
      treatment-resistant depression. The higher the stage, the greater the need for
      complex and specialised treatment. As characteristics for profiling we
      distinguish (a) aetiological and pathophysiological variables and (b) clinical
      factors. The latter are the ones that mainly influence treatment from stage 2
      onwards. CONCLUSION: In our article we give a tentative overview of possible
      characteristics for profiling. At the moment the clinical factors are the ones
      used most for assessment. Current research into the value of aetiological
      characteristics for profiling will increase the applicability of a staging and
      profiling model.

PMID- 23138624
TI  - [The challenge of staging developmental disorders].
AB  - BACKGROUND: On the basis of our current knowledge, developmental disorders can be
      divided into the following stages: stage 0: normal variation, stage 1: simple
      disorder of moderate severity, stage 2: complicating co-morbidity and/or harmful
      background circumstances, and stage 3: serious disorder with harmful background
      circumstances. AIM: To describe the current views on prognostic aspects of
      staging from a developmental perspective. METHOD: The study is based on a
      critical review of the relevant literature. RESULTS: The current division into
      stages is still insufficiently predictive, partly because development is a
      flexible process with risks, chances and second chances. All psychiatric
      disorders are in essence developmental disorders that arise in the course of
      development as a result of the interaction between predisposition and background
      circumstances. As from the very first meiosis the hereditary predisposition is
      subject to influences in the womb environment. The forming of networks in the
      brain, the distribution of neurotransmitters and the neurological profile are
      influenced by the genetic potential for chances and risks and are all a result of
      interactions. This complicated developmental history raises questions about the
      specificity of current clinical syndromes. CONCLUSION: In time there is likely to
      be a much more accurate staging system. This will come about if, as a result of
      the analysis of large pooled databases, it becomes possible to make a better
      assessment of the relative risks of genetic configurations, brain connections,
      stress regulation in the brain, neuropsychological profiles and behavioural and
      emotional forms of expression in the light of the interactions that occur with
      the aforementioned background circumstances.

PMID- 23138625
TI  - [Staging with profiles in offence analysis: diagnostic steps in forensic
      psychiatry].
AB  - BACKGROUND: Forensic psychiatry is concerned particularly with accurate risk
      assessment of offenders' future behaviour. AIM: To describe a staging and
      profiling system that is applicable to mentally-ill patients who have committed
      an offence. METHOD: The various steps in forensic psychiatric diagnosis are
      analysed and discussed. RESULTS: Three diagnostic steps within a treatment
      trajectory are described: stage 1. psychiatric diagnosis; stage 2. the course of
      the trajectory; stage 3. supervision (i.e. protection from danger). Each step is
      divided into profiles. CONCLUSION: By means of staging and profiling, the
      treatment plan is integrated into a dynamic model in which each stage contains a
      set of activities that gradually lead to unique profiles and interventions which
      incorporate evidence for subsequent diagnostics.

PMID- 23138626
TI  - [Staging, profiling and routine outcome monitoring].
AB  - BACKGROUND: Staging and profiling can make a valuable contribution to more
      effective and tailor-made treatments. In psychiatry these techniques have so far
      played only a very limited role. Routine outcome monitoring ROM ) may be able to
      alter the situation. AIM: To describe the criteria of a ROM-system that is ideal
      for staging and profiling and to find out to what extent some existing rom
      systems satisfy these criteria. METHOD: The method used was to investigate to
      what extent the minimal dataset of the Stichting Benchmark GGZ and the ROM of the
      Leiden Routine Outcome Monitoring Study meet the criteria formulated in this
      article for an ideal ROM and provide a 'proof of principle'. RESULTS: The minimal
      dataset of the Stichting Benchmark ggz satisfies fewer criteria than the ROM of
      the Leiden Routine Outcome Monitoring Study, but neither fulfils all the
      criteria. Nevertheless, even without adequate datasets the Leiden Routine Outcome
      Monitoring Study can make a useful contribution to the staging of depression and
      mental health in general and to the profiling of depression. CONCLUSION: ROM is
      an important instrument for the development of staging and profiling in
      psychiatry.

PMID- 23138627
TI  - [Can staging and profiling ensure that the costs of quality care are adequately
      reimbursed?].
AB  - BACKGROUND: The current system for financing effective mental health can improve
      or reduce the quality of care provided. The system of financing includes
      reimbursing the care-provider, a risk-adjustment system for the health insurer
      and personal payments by the patient. Care-providers, patients and health
      insurers are worried that the current system is detrimental to quality care. AIM:
      To find out whether the financing system can be improved by the introduction of a
      system which weighs the costs according to the intensity of the care provided and
      which is based on staging and profiling. METHOD: We performed a critical
      evaluation of the current financing system and we explored how staging and
      profiling could help to keep complex care affordable. RESULTS: The current model
      for financing mental health care does not involve staging and profiling.
      Reimbursement is based on diagnoses and on the number of minutes of care
      provided, no differentiation being made between the levels of expertise required.
      As a result it can become financially unattractive to administer the best
      possible treatment to patients with the greatest needs. Staging and profiling
      have the potential to create the best possible relationship between the level of
      care needed by the patient and the treatment costs incurred, because the factors
      that led to the previous imbalance have been removed. CONCLUSION: Staging and
      profiling can be introduced gradually at roughly the same pace as the national
      system of risk-adjustment is being introduced for health insurers.

PMID- 23138628
TI  - The time course of attentional deployment in contextual cueing.
AB  - The time course of attention is a major characteristic on which different types
      of attention diverge. In addition to explicit goals and salient stimuli, spatial
      attention is influenced by past experience. In contextual cueing, behaviorally
      relevant stimuli are more quickly found when they appear in a spatial context
      that has previously been encountered than when they appear in a new context. In
      this study, we investigated the time that it takes for contextual cueing to
      develop following the onset of search layout cues. In three experiments,
      participants searched for a T target in an array of Ls. Each array was
      consistently associated with a single target location. In a testing phase, we
      manipulated the stimulus onset asynchrony (SOA) between the repeated spatial
      layout and the search display. Contextual cueing was equivalent for a wide range
      of SOAs between 0 and 1,000 ms. The lack of an increase in contextual cueing with
      increasing cue durations suggests that as an implicit learning mechanism,
      contextual cueing cannot be effectively used until search begins.

PMID- 23138630
TI  - Karyological studies in Brazilian species of Lippia L. (Verbenaceae).
AB  - The genus Lippia (Verbenaceae) comprise around 160 species spread out mainly in
      South and Central Americas with few African species, some of them with potential
      medicinal use. Brazil is one the most important centers of diversity with
      approximately 75% of the species described so far. Innumerous species are endemic
      and poorly studied especially at a cytological level. Here, chromosomal length,
      karyomorphology and chromosome asymmetry of twelve Brazilian species of Lippia
      were evaluated [L. alba (Miller) N.E.Brown, L. diamantinensis Glaz., L. florida
      Cham., L. hermanioides Cham., L. lacunosa Mart. & Schauer, L. lupulina Cham., L.
      pohliana Schauer, L. pseudothea (St. Hil) Schauer, L. rosella Moldenke, L.
      rotundifolia Cham., L. rubella Moldenke and L. sidoides Cham.]. The analysis
      suggested that the genus has a variable chromosome number (from 2n = 20 to 2n =
      56) originated by dysploidy and polyploidy. This is the first description of
      chromosome morphology for 11 of the 12 Lippia species studied.

PMID- 23138631
TI  - Metabolic syndrome in the offspring of centenarians: focus on prevalence,
      components, and adipokines.
AB  - With aging, an increased prevalence of a clustering of metabolic abnormalities
      has been observed. These abnormalities include obesity, dyslipidemia,
      hypertension, and insulin resistance and are collectively known as metabolic
      syndrome (MetS), a low-grade, systemic, inflammatory condition associated with an
      increased risk of cardiovascular disease, diabetes, and other adverse health
      outcomes. A number of studies have demonstrated that centenarians' offspring have
      a significant survival advantage and a lower risk of developing the most
      important age-related diseases. They therefore represent one of the best models
      with which to study the familiar component of human longevity. The aim of this
      study was to determine if the offspring of centenarians (n = 265 subjects) showed
      a different prevalence of MetS in comparison to the offspring of non-long-lived
      parents (controls, n = 101 subjects). In addition, we assessed whether
      centenarians' offspring showed particular features of MetS and a distinct
      regulation of circulating adipokines, cytokines, and metabolic mediators.
      Although the prevalence of MetS was quite similar both in the offspring of
      centenarians and the controls, MetS-affected centenarians' offspring seemed
      healthier, more functionally fit, and had lower resistin levels. MetS prevalence
      did not change in centenarians' offspring across resistin, IGF-1, and
      resistin/IGF-1 ratio tertiles. On the other hand, in controls, MetS prevalence
      strongly increased across resistin tertiles and in the third resistin/IGF-1 ratio
      tertile, indicating a dramatic increase in MetS prevalence when the ratio between
      these two factors is unbalanced, with high levels of resistin and low levels of
      IGF-1.

PMID- 23138632
TI  - Coenzyme Q(10) supplementation reverses age-related impairments in spatial
      learning and lowers protein oxidation.
AB  - Coenzyme Q10 (CoQ) is widely available as a dietary supplement and remains under
      consideration as a treatment for age-associated neurodegenerative conditions.
      However, no studies have determined if supplementation, initiated relatively late
      in life, could have beneficial effects on mild functional impairments associated
      with normal brain aging. Accordingly, the current study assessed the effect of
      CoQ intake in older mice for which cognitive and psychomotor impairments were
      already evident. Separate groups of young (3.5 months) and relatively old mice
      (17.5 months) were fed a control diet or a diet supplemented with low (0.72 mg/g)
      or high (2.81 mg/g) concentrations of CoQ for 15 weeks. After 6 weeks, the mice
      were given tests for spatial learning (Morris water maze), spontaneous locomotor
      activity, motor coordination, and startle reflex. Age-related impairments in
      cognitive and psychomotor functions were evident in the 17.5-month-old mice fed
      the control diet, and the low-CoQ diet failed to affect any aspect of the
      impaired performance. However, in the Morris water maze test, old mice on the
      high-CoQ diet swam to the safe platform with greater efficiency than the mice on
      the control diet. The old mice supplemented with the high-CoQ diet did not show
      improvement when spatial performance was measured using probe trials and failed
      to show improvement in other tests of behavioral performance. Protein oxidative
      damage was decreased in the mitochondria from the heart, liver, and skeletal
      muscle of the high-CoQ-supplemented mice and, to some extent, in the brain
      mitochondria. Contrasting with the deleterious effect of long-term CoQ
      supplementation initiated during young adulthood previously published, this study
      suggests that CoQ improves spatial learning and attenuates oxidative damage when
      administered in relatively high doses and delayed until early senescence, after
      age-related declines have occurred. Thus, in individuals with age-associated
      symptoms of cognitive decline, high-CoQ intake may be beneficial.

PMID- 23138633
TI  - The motilin gene evolved a new function in kangaroo rats and kangaroo mice
      (Dipodomyinae).
AB  - The motilin receptor gene was lost in the ancestral lineage of rodents.
      Subsequently, the gene encoding its ligand, motilin, has experienced different
      evolutionary fates. Previous genomic analyses had shown that the motilin gene
      (MLN) became a pseudogene independently in the lineages leading to the guinea pig
      and the common ancestor of the mouse and rat, yet an intact, and thus potentially
      functional, open reading frame for the MLN was preserved in the Dipodomys ordii
      genome. As only a single MLN haplotype from D. ordii was available, and this
      sequence is from a low coverage draft genome, it is possible that the intact MLN
      found in the draft kangaroo rat genome is an artifact, or represents an
      intermediate in the process of becoming a pseudogene. In order to establish
      whether an intact MLN is retained in kangaroo rats despite the loss of its
      specific receptor, and to investigate the evolutionary mechanisms underlying the
      retention of this gene sequence, we isolated MLN sequences from species that
      represent the diversity of the Dipodomyinae [the monophyletic Dipodomyinae
      subfamily consists of two genera: Dipodomys (kangaroo rats) and Microdipodops
      (kangaroo mice)]. The results demonstrate that the MLN sequence is well conserved
      in Dipodomyinae, and it codes for a predicted motilin peptide sequence possessing
      a conserved N-terminal pharmacophore and the potential to be processed and
      secreted as a hormone. The observations that the MLN evolved as a functional gene
      during the radiation of the Dipodomyinae, species that have lost their original
      motilin receptor, suggest that the MLN has undergone a lineage-specific
      physiological adaptation to a new function.

PMID- 23138634
TI  - Compositional bias is a major determinant of the distribution pattern and
      abundance of palindromes in Drosophila melanogaster.
AB  - Palindromic sequences are important DNA motifs related to gene regulation, DNA
      replication and recombination, and thus, investigating the evolutionary forces
      shaping the distribution pattern and abundance of palindromes in the genome is
      substantially important. In this article, we analyzed the abundance of
      palindromes in the genome, and then explored the possible effects of several
      genomic factors on the palindrome distribution and abundance in Drosophila
      melanogaster. Our results show that the palindrome abundance in D. melanogaster
      deviates from random expectation and the uneven distribution of palindromes
      across the genome is associated with local GC content, recombination rate, and
      coding exon density. Our data suggest that base composition is the major
      determinant of the distribution pattern and abundance of palindromes and the
      correlation between palindrome density and recombination is a side-product of the
      effect of compositional bias on the palindrome abundance.

PMID- 23138635
TI  - Magnetization transfer for the assessment of bowel fibrosis in patients with
      Crohn's disease: initial experience.
AB  - OBJECT: To assess the feasibility of magnetization transfer (MT) imaging of the
      bowel wall in patients with Crohn's disease (CD), and to evaluate its utility for
      the detection of intestinal fibrosis. MATERIALS AND METHODS: In this prospective
      study, 31 patients (age 39.0 +/- 13.2 years) with CD were examined in a 1.5T MR
      scanner. To establish a standard of reference, two independent readers classified
      the patients in different disease states using standard MR enterography,
      available clinical data and histological findings. In addition to the standard
      protocol, a 2D gradient-echo sequence (TR/TE 32 ms/2.17 ms; flip angle 25 degrees
      ) with/without 1,100 Hz off-resonance prepulse was applied. MT ratios (MTR) of
      the small bowel wall were computed off-line on a pixel-by-pixel basis. RESULTS:
      The MT sequences acquired images of sufficient quality and spatial resolution for
      the evaluation of the small bowel wall without detrimental motion artefacts. In
      normal bowel wall segments, an intermediate MTR of 25.4 +/- 3.4 % was measured.
      The MTR was significantly increased in bowel wall segments with fibrotic scarring
      (35.3 +/- 4.0 %, p < 0.0001). In segments with acute inflammation, the mean MTR
      was slightly smaller (22.9 +/- 2.2 %). CONCLUSION: MT imaging of the small bowel
      wall is feasible in humans with sufficient image quality and may help with the
      identification of fibrotic scarring in patients with CD.

PMID- 23138636
TI  - Influence of dual-task performance on muscle and brain activity.
AB  - The simultaneous performance of multiple tasks is often required in daily life.
      The dual-task paradigm has been used extensively to evaluate the ability to
      perform simultaneous behavioral tasks. However, relatively few studies have been
      carried out to determine the muscle and brain activity underlying dual-task
      performance. This study determined the influence of single-task and dual-task
      conditions on muscle and brain activity by measuring ankle dorsiflexion, surface
      electromyography, and magnetoencephalography. Increased muscle activation and
      variability in the dorsiflexion interval was observed during dual-task
      performance compared with single-task performance, whereas brain activity in the
      contralateral motor and frontal areas was reduced. Incidental movement of the non
      task-related ankle (contralateral ankle) showed a different pattern of brain
      activity during the dual-task performance in another experiment. These findings
      suggest that the activity decreased in several information-processing areas under
      dual-task conditions as a result of decentralization of attention. Activity in
      the right and left motor fields may play a role in the dual-task performance, as
      indicated by changes in brain activity during dual-task performance in two groups
      classified according to the activity level of the contralateral ankle.

PMID- 23138637
TI  - Growth modeling of CdTe nanowires.
AB  - Au-catalyzed CdTe nanowires have been grown by close-space sublimation on Mo
      foils via the vapor-liquid-solid technique. Nanowire length (up to 25 MUm)
      increased as a function of growth temperature and time. Nanowire average radius
      only started to increase after 20 min of growth. A model has been developed to
      quantitatively describe this observed growth behavior. The model takes into
      account the simultaneous lateral extension of nanowires (radii were in the range
      150-550 nm), observed for longer growth times. Fitting the model to the
      experimental data yields a number of kinetic parameters. More importantly, the
      threshold character of the radius-time dependence as well as the essentially non
      linear shape of the length-time relationship is well reproduced by the model.

PMID- 23138640
TI  - Tuning the interactions from antiferro- to ferro-magnetic by molecular tailoring
      and manipulating.
AB  - Four novel Cu(II) complexes {Na[Cu(4)(hmp)(4)(CHOO)(3)](ClO(4))(2).H(2)O}(n) (1),
      [Cu(8)(hmp)(8)(CH(3)COO)(6)](ClO(4))(2) (2),
      [Cu(4)(hmp)(4)(CH(3)CN)(2)(ClO(4))(2)(H(2)O)(2)](ClO(4))(2) (3), and
      [Cu(4)(hmp)(4)(CH(3)COO)(2)(H(2)O)(4)](ClO(4))(2).2H(2)O (4) with Hhmp = 2
      (hydroxymethyl)pyridine were prepared by structural modulation at room
      temperature. Taking advantage of the steric hindrance of the ancillary ligands,
      the 1D copper chain (1) is successfully cut down into the octa-nuclear copper
      cluster (2) with the unchanged antiferromagnetic [Cu(4)O(4)] open-cubane that is
      further separated into weak antiferromagnetic [Cu(4)O(4)] (3) and then modulated
      to be the ferromagnetic tetra-nuclear [Cu(4)O(4)] cluster (4). The obtained four
      complexes allow us to systematically investigate their magnetic properties and
      find the rules for further magnetic investigations. The results showed that there
      exist antiferromagnetic interactions between Cu(ii) ions in 1-3, while 4 displays
      ferromagnetic behaviour. The best fitting results to the experimental magnetic
      susceptibilities gave J(1) = J(2) = J(3) = -2.26 cm(-1), g = 2.11 for 3 and J(1)
      = 37.05 cm(-1), J(2) = -0.62 cm(-1), J(3) = -0.62 cm(-1), g = 2.13 for 4.

PMID- 23138639
TI  - Recent advances in nanopore sequencing.
AB  - The prospect of nanopores as a next-generation sequencing platform has been a
      topic of growing interest and considerable government-sponsored research for more
      than a decade. Oxford Nanopore Technologies recently announced the first
      commercial nanopore sequencing devices, to be made available by the end of 2012,
      while other companies (Life, Roche, and IBM) are also pursuing nanopore
      sequencing approaches. In this paper, the state of the art in nanopore sequencing
      is reviewed, focusing on the most recent contributions that have or promise to
      have next-generation sequencing commercial potential. We consider also the
      scalability of the circuitry to support multichannel arrays of nanopores in
      future sequencing devices, which is critical to commercial viability.

PMID- 23138641
TI  - Axial dispersion in packed bed reactors involving viscoinelastic and viscoelastic
      non-Newtonian fluids.
AB  - Axial dispersion is an important parameter in the performance of packed bed
      reactors. A lot of fluids exhibit non-Newtonian behaviour but the effect of
      rheological parameters on axial dispersion is not available in literature. The
      effect of rheology on axial dispersion has been analysed for viscoinelastic and
      viscoelastic non-Newtonian fluids. Aqueous solutions of carboxymethyl cellulose
      and polyacrylamide have been chosen to represent viscoinelastic and viscoelastic
      liquid-phases. Axial dispersion has been measured in terms of BoL number. The
      single parameter axial dispersion model has been applied to analyse RTD response
      curve. The BoL numbers were observed to increase with increase in liquid flow
      rate and consistency index 'K' for viscoinelastic as well as viscoelastic fluids.
      Bodenstein correlation for Newtonian fluids proposed has been modified to account
      for the effect of fluid rheology. Further, Weissenberg number is introduced to
      quantify the effect of viscoelasticity. 

PMID- 23138642
TI  - Effect of organic acids found in cottonseed hull hydrolysate on the xylitol
      fermentation by Candida tropicalis.
AB  - Five organic acids (acetic, ferulic, 4-hydroxybenzoic, formic and levulinic
      acids) typically associated in the hemicellulose hydrolysate were selected to
      study their effects on the xylitol fermentation. The effects of individual and
      combined additions were independently evaluated on the following parameters:
      inhibitory concentration; initial cell concentration; pH value; and membrane
      integrity. The results showed that the toxicities of organic acids were related
      to their hydrophobility and significantly affected by the fermentative pH value.
      In addition, it was revealed that the paired combinations of organic acids did
      not impose synergetic inhibition. Moreover, it was found that the fermentation
      inhibition could be alleviated with the simple manipulations by increasing the
      initial cell concentration, raising the initial pH value and minimizing furfural
      levels by evaporation during the concentration of hydrolysates. The proposed
      strategies for minimizing the negative effects could be adopted to improve the
      xylitol fermentation in the industrial applications. 

PMID- 23138644
TI  - Ethynyl-linked push-pull porphyrin hetero-dimers for near-IR dye-sensitized solar
      cells: photovoltaic performances versus excited-state dynamics.
AB  - Ethynyl-linked porphyrin hetero-dimers substituted by a series of electron
      donors, namely, bis(4-methoxyphenyl)amino (BMPA), bis(4-tert-butylphenyl)amino
      (BTBPA) and 3,6-di-tert-butylcarbazol-9-yl (DTBC) as well as a reference dimer
      with a non-donor moiety (3,5-di-tert-butylphenyl, DTBP) have been synthesized to
      systematically investigate the influence of donor introduction on the
      photovoltaic performances of near-IR dye-sensitized solar cells (DSCs) with these
      sensitizers incorporated. Despite the expected bathochromic shift and
      intensification of long-wavelength absorption bands as well as elevated LUMO
      levels and thus increased electron injection driving forces, the substitution of
      diphenylamino groups (BMPA and BTBPA) with stronger electron-donating abilities
      gave rise to surprising mediocrity in the short-circuit photocurrent densities
      (J(sc)), leading to overall energy conversion efficiencies in the order BMPA
      (3.94%) < DTBP (4.57%) < BTBPA (4.83%) < DTBC (5.21%). A study of the in situ
      fluorescent behavior of these sensitizers revealed that for all the sensitizers,
      excited-state lifetimes were significantly shortened in the simulated DSC
      environment compared to those in a free solution. BMPA showed the shortest
      intrinsic in situ lifetime while DTBC showed the longest one. These results were
      correlated with the photovoltaic performances, which is required for a better
      understanding and further design of porphyrin array sensitizers.

PMID- 23138643
TI  - Theoretical study on the binding mechanism between N6-methyladenine and natural
      DNA bases.
AB  - N6-methyladenine (m(6)A) is a rare base naturally occurring in DNA. It is
      different from the base adenine due to its N-CH(3). Therefore, the base not only
      pairs with thymine, but also with other DNA bases (cytosine, adenine and
      guanine). In this work, Moller-Plesset second-order (MP2) method has been used to
      investigate the binding mechanism between m(6)A and natural DNA bases in gas
      phase and in aqueous solution. The results show that N-CH(3) changed the way of
      N6-methyladenine binding to natural DNA bases. The binding style significantly
      influences the stability of base pairs. The trans-m(6)A:G and trans-m(6)A:C
      conformers are the most stable among all the base pairs. The existence of solvent
      can remarkably reduce the stability of the base pairs, and the DNA bases prefer
      pairing with trans-m(6)A to cis-m(6)A. Besides, the properties of these hydrogen
      bonds have been analyzed by atom in molecules (AIM) theory, natural bond orbital
      (NBO) analysis and Wiberg bond indexes (WBI). In addition, pairing with m(6)A
      decreases the binding energies compared to the normal Watson-Crick base pairs, it
      may explain the instability of the N6 site methylated DNA in theory.

PMID- 23138645
TI  - The effects of guided imagery on sleep and inflammatory response in cardiac
      surgery: a pilot randomized controlled trial.

PMID- 23138638
TI  - Muscle development, regeneration and laminopathies: how lamins or lamina
      associated proteins can contribute to muscle development, regeneration and
      disease.
AB  - The aim of this review article is to evaluate the current knowledge on
      associations between muscle formation and regeneration and components of the
      nuclear lamina. Lamins and their partners have become particularly intriguing
      objects of scientific interest since it has been observed that mutations in genes
      coding for these proteins lead to a wide range of diseases called laminopathies.
      For over the last 10 years, various laboratories worldwide have tried to explain
      the pathogenesis of these rare disorders. Analyses of the distinct aspects of
      laminopathies resulted in formulation of different hypotheses regarding the
      mechanisms of the development of these diseases. In the light of recent
      discoveries, A-type lamins--the main building blocks of the nuclear lamina-
      together with other key elements, such as emerin, LAP2alpha and nesprins, seem to
      be of great importance in the modulation of various signaling pathways
      responsible for cellular differentiation and proliferation.

PMID- 23138646
TI  - Clinical outcome of the PAS-Port(r) proximal anastomosis system in off-pump
      coronary artery bypass grafting in 201 patients.
AB  - AIM: The PAS-Port(r) Proximal Anastomosis System (Cardica, Inc, Redwood City, CA,
      USA) has been used worldwide since March 2003. The objective of the present study
      was to evaluate the clinical outcome of the PAS-Port(r) Proximal Anastomosis
      System. METHODS: All the patients who underwent off-pump coronary artery bypass
      grafting in the Catharina Hospital Eindhoven between August 2006 and April 2010
      were included in a non-randomized retrospective case-control study, if they had
      at least one proximal vein graft anastomosis. Study end-points consisted of
      overall survival, coronary reintervention and postoperative stroke. RESULTS: The
      study included 312 patients (201 cases, 111 controls). After 36 months of follow
      up there was no difference in survival between cases and controls (92.2% vs.
      93.7%, P=0.52). No significant difference could be detected between cases and
      controls with respect to overall coronary reintervention-free survival (93% vs.
      96.4%, P=0.20) and freedom from coronary reintervention due to proximal vein
      graft failure (98% vs. 100% P=0.14). The use of the PAS-Port system could not be
      identified as an independent risk factor of coronary reintervention (p=0.21).
      Postoperative stroke rates of cases and controls (2% vs. 0.9%, P=0.42) were
      comparable. CONCLUSION: The clinical outcomes in patients treated with the PAS
      Port(r) Proximal Anastomosis System were satisfactory compared with those treated
      with the conventional hand-sewing technique. The use of the PAS-Port system was
      not associated with higher adverse outcome in terms of overall survival, stroke,
      coronary reintervention-free survival and freedom from reintervention due to
      proximal vein graft failure.

PMID- 23138647
TI  - Claimants in vascular surgery.
AB  - AIM: Litigation concerning medical activities is constantly increasing, as
      society becomes more and more "protective" of citizens who may have suffered any
      wrong due to malpractice. However, we should bear in mind that the percentage of
      claims liquidated is minimal. METHODS: From January 2009 to December 2011, 63
      claims involving vascular procedures were analyzed. The rate of claimants
      receiving payment was very low: only 8 of the 63 (12.7%) claims having been
      settled. The most important thing we noted was that in 5 of the 8 claims settled
      the key element that defined the sentence was time: time to take a decision, to
      perform a diagnostic examination, to decide on a surgical procedure. RESULTS: We
      have sought to assess the role of the "time factor" in the occurrence of errors
      in a surgical specialty considered at high risk of litigation such as vascular
      surgery. This analysis of our experience over the past three years has shown that
      the central element in the genesis of the error was the erroneous timing of
      intervention. It interesting to note that, in contrast to what might be expected,
      time-related errors are much more common in cases treated electively than in
      urgent or emergency cases. CONCLUSION: Our experience demonstrates that the "time
      factor" plays a primary role in the genesis of errors in vascular surgery. This
      delay in deciding and acting probably depends on the fact that the vascular
      surgeon was the patient's first contact in only one of the cases examined. This
      should emphasize the need to equip all emergency departments with a Vascular
      Surgery Unit.

PMID- 23138648
TI  - Medical service encounters and payments associated with topical adjunctive
      therapy use of timolol for glaucoma.
AB  - BACKGROUND: Topical beta-blockers are commonly prescribed for primary open-angle
      glaucoma. Existing research is limited regarding respiratory or cardiovascular
      events that may result from using these topical beta-blockers. OBJECTIVE: To
      evaluate inpatient and outpatient service encounters and payments associated with
      the topical adjunctive use of the beta-blocker timolol for glaucoma. STUDY
      DESIGN: Retrospective data analysis using 2004-2011 IMS Lifelink Health Plan
      Claims Database. PATIENTS: Beneficiaries were included if they had a diagnosis of
      glaucoma (International Classification of Diseases-Ninth Revision-Clinical
      Modification [ICD-9-CM] code 365.xx) and at least 4 years of continuous
      enrollment and glaucoma medication use (defined as at least one pharmacy claim
      each year). Beneficiaries who had 4 years of observation with no timolol use were
      categorized as "controls" and those with 2 years of non-timolol glaucoma
      medication use followed by consecutive years of adjunctive timolol use were
      considered "cases." Beneficiaries with 2 years of non-timolol glaucoma medication
      use followed by 1 year in which they used timolol adjunctively and then a year
      without timolol use were considered "discontinuers." MAIN OUTCOME MEASURE: The
      rates of respiratory and cardiovascular disease in year 2 of the observation
      period were compared to the rates in year 3, and healthcare encounters and
      payments were also compared. RESULTS: There were 24,271 glaucoma patients who did
      not receive timolol (controls), 1,406 beneficiaries who were prescribed timolol
      in addition to other glaucoma medications and continued its use (cases), and 299
      beneficiaries who used adjunctive timolol for only a single year (discontinuers).
      More than half of each group was less than 65 years of age (58 % of controls, 53
      % of cases, 54 % of discontinuers, p < 0.05). The rate of respiratory disease
      increased in all groups from year 2 to year 3 of the observation period, with
      increases of 1.0 %, 1.4 % and 5.0 % points among controls, cases and
      discontinuers, respectively (all between-group comparisons significant at p <
      0.05). There were similar changes in the rate of cardiovascular disease, with
      increases of 1.3 %, 1.5 % and 4.7 % points among controls, cases and
      discontinuers, respectively (all between-group comparisons significant at p <
      0.05). These increases were generally lower for younger beneficiaries and greater
      for those 65 years and older. Comparing years 2 and 3 of the observation period,
      discontinuers more than doubled their average rate of all-cause inpatient
      hospitalizations (0.35-0.83 encounters annually), while this rate remained steady
      for cases and controls (between-group comparisons significant at p < 0.05). There
      was little change in this rate among patients less than 65 years of age. Among
      those aged 65 years and older, there was a substantial increase for
      discontinuers, with a tripling of the average annual rate of inpatient
      hospitalizations from 0.45 to 1.48 (all between-group comparisons significant at
      p < 0.05). In this older group, both discontinuers and cases experienced more
      than a 20 % increase in outpatient service encounters compared to only 9 % for
      controls (all between-group comparisons significant at p < 0.05). Overall,
      discontinuers would be expected to have average annual medical payments US$3,600
      greater than controls and US$3,200 greater than cases. CONCLUSION: Adjunctive use
      of timolol by patients with glaucoma may be associated with increased respiratory
      and/or cardiovascular disease, hospitalizations and payments among patients for
      whom timolol may be contraindicated or who have yet undiagnosed manifestations of
      conditions for which it would be contraindicated.

PMID- 23138649
TI  - Genes regulating the B cell receptor pathway are recurrently mutated in primary
      central nervous system lymphoma.

PMID- 23138651
TI  - Arsenite tolerance is related to proportional thiolic metabolite synthesis in
      rice (Oryza sativa L.).
AB  - Thiol metabolism is the primary detoxification strategy by which rice plants
      tolerate arsenic (As) stress. In light of this, it is important to understand the
      importance of harmonised thiol metabolism with As accumulation and tolerance in
      rice plant. For this aim, tolerant (T) and sensitive (S) genotypes were screened
      from 303 rice (Oryza sativa) genotypes on exposure to 10 and 25 MUM arsenite
      (As(III)) in hydroponic culture. On further As accumulation estimation,
      contrasting (13-fold difference) T (IC-340072) and S (IC-115730) genotypes were
      selected. This difference was further evaluated using biochemical and molecular
      approaches to understand involvement of thiolic metabolism vis-a-vis As
      accumulation in these two genotypes. Various phytochelatin (PC) species (PC(2),
      PC(3) and PC(4)) were detected in both the genotypes with a dominance of PC(3).
      However, PC concentrations were greater in the S genotype, and it was noticed
      that the total PC (PC(2) + PC(3 )+ PC(4))-to-As(III) molar ratio (PC-SH:As(III))
      was greater in T (2.35 and 1.36 in shoots and roots, respectively) than in the S
      genotype (0.90 and 0.15 in shoots and roots, respectively). Expression analysis
      of several metal(loid) stress-related genes showed significant upregulation of
      glutaredoxin, sulphate transporter, and ascorbate peroxidase in the S genotype.
      Furthermore, enzyme activity of phytochelatin synthase and cysteine synthase was
      greater on As accumulation in the S compared with the T genotype. It was
      concluded that the T genotype synthesizes adequate thiols to detoxify metalloid
      load, whereas the S genotype synthesizes greater but inadequate levels of thiols
      to tolerate an exceedingly greater load of metalloids, as evidenced by thiol-to
      metalloid molar ratios, and therefore shows a phytotoxicity response.

PMID- 23138650
TI  - Presenilin-1 adopts pathogenic conformation in normal aging and in sporadic
      Alzheimer's disease.
AB  - Accumulation of amyloid-beta (Abeta) and neurofibrillary tangles in the brain,
      inflammation and synaptic and neuronal loss are some of the major
      neuropathological hallmarks of Alzheimer's disease (AD). While genetic mutations
      in amyloid precursor protein and presenilin-1 and -2 (PS1 and PS2) genes cause
      early-onset familial AD, the etiology of sporadic AD is not fully understood. Our
      current study shows that changes in conformation of endogenous wild-type PS1,
      similar to those found with mutant PS1, occur in sporadic AD brain and during
      normal aging. Using a mouse model of Alzheimer's disease (Tg2576) that
      overexpresses the Swedish mutation of amyloid precursor protein but has normal
      levels of endogenous wild-type presenilin, we report that the percentage of PS1
      in a pathogenic conformation increases with age. Importantly, we found that this
      PS1 conformational shift is associated with amyloid pathology and precedes
      amyloid-beta deposition in the brain. Furthermore, we found that oxidative
      stress, a common stress characteristic of aging and AD, causes pathogenic PS1
      conformational change in neurons in vitro, which is accompanied by increased
      Abeta42/40 ratio. The results of this study provide important information about
      the timeline of pathogenic changes in PS1 conformation during aging and suggest
      that structural changes in PS1/gamma-secretase may represent a molecular
      mechanism by which oxidative stress triggers amyloid-beta accumulation in aging
      and in sporadic AD brain.

PMID- 23138652
TI  - Thoracoamniotic shunting for fetal pleural effusions using a double-basket shunt.
AB  - OBJECTIVE: To describe the safety and efficacy of thoracoamniotic shunting for
      fetal pleural effusion using a double-basket catheter with a very small diameter
      (1.47 mm). METHOD: In this 2-year multicenter, prospective single-arm clinical
      study registered with the University hospital Medical Information Network (UMIN)
      Clinical Trials Registry (UMIN00001095); shunting was performed between 18w0d and
      33w6d of gestation with this catheter in cases of fetal pleural effusions
      reaccumulating after thoracocentesis. The primary endpoint measures were maternal
      and fetal adverse effects and survival in the neonatal period. RESULTS: A total
      of 24 cases were included, of which 17 had hydrops (71%). The median gestational
      ages at shunting and delivery were 27.4 and 34.8 weeks, respectively. There were
      no fetal deaths, lung injuries, or severe maternal complications. Preterm rupture
      of the membranes occurred in 7/24 (29%) cases at a median of 62 days after the
      shunting. Preterm rupture of the membranes within 28 days of the procedure
      occurred in 1/24 (4%) cases. Catheter displacement towards the fetal thoracic
      cavity occurred in 4/42 (10%) cases. The overall survival rate was 79% (19/24),
      whereas it was 71% (12/17) in the cases with hydrops. CONCLUSION: Drainage of
      fetal pleural effusions with a double-basket shunt is safe and effective, and the
      shunt could be an alternative device.

PMID- 23138654
TI  - Protein-associated cation clusters in aqueous arginine solutions and their
      effects on protein stability and size.
AB  - Arginine is one of the most prominent residues in protein interactions, and
      arginine hydrochloride is widely used as an additive in protein solutions because
      of its exceptional effects on protein association and folding. The molecular
      origins of arginine effects on protein processes remain, however, controversial,
      and little is known about the molecular interactions between arginine cations and
      protein surfaces in aqueous arginine solutions. In this study, we report a unique
      biochemical phenomenon whereby clusters of arginine cations (Arg(+)) are
      associated with a protein surface. The formation of protein-associated Arg(+)
      clusters is initiated by Arg(+) ions that associate with specific protein surface
      loci through cooperative interactions with protein guanidinium and carboxyl
      groups. Molecular dynamics simulations indicate that protein-associated Arg(+)
      ions subsequently attract other Arg(+) ions and form dynamic cation clusters that
      extend further than 10 A from the protein surface. The effects of arginine on the
      thermal stability and size of lysozyme and ovalbumin are measured over a wide
      concentration range (0 to 2 M), and we find that the formation of protein
      associated Arg(+) clusters consistently explains the complex effects of arginine
      on protein stability and size. This study elucidates the molecular mechanisms and
      implications of cluster formation of Arg(+) ions at a protein surface, and the
      findings of this study may be used to manipulate synthetic and biological systems
      through arginine-derived groups.

PMID- 23138653
TI  - The role of C-terminal binding protein 2 in Schwann cell differentiation after
      sciatic nerve crush.
AB  - C-terminal binding protein 2 (CtBP2), as a transcriptional repressor, plays an
      essential role in development and tumorigenesis. However, its distribution and
      function in peripheral system lesion and repair are still unknown. Here, we
      investigated the spatiotemporal expression of CtBP2 in rat sciatic nerve crush
      model. Western blot analysis revealed that CtBP2 was expressed in normal sciatic
      nerve. It gradually decreased, reached minimal levels at 7 days after crush, and
      then returned to the normal level at 4 weeks. We observed that CtBP2 is mainly
      expressed in Schwann cells (SCs). In vitro, we induced SC differentiation via
      cyclic adenosine monophosphate (cAMP) and found that CtBP2 expression was
      downregulated during the process of differentiation. CtBP2-specific siRNA
      inhibited the cAMP-induced expression of the immature SC marker P75(NTR), and
      exogenous CtBP2 expression upregulated the expression of P75(NTR). Taken
      together, we hypothesized that peripheral nerve crush-induced downregulation of
      CtBP2 in the sciatic nerve was associated with SC differentiation, and CtBP2
      likely played an important role in peripheral nerve injury and regeneration.

PMID- 23138655
TI  - Hierarchically assembled Au microspheres and sea urchin-like architectures:
      formation mechanism and SERS study.
AB  - The hierarchically assembled Au microspheres/sea urchin-like structures have been
      synthesized in aqueous solution at room temperature with and without proteins
      (bovine serum albumin, BSA) as mediators. The average diameter of an individual
      Au microsphere is 300-600 nm, which is composed of some compact nanoparticles
      with an average diameter of about 15 nm. Meanwhile, the sea urchin-like Au
      architecture exhibits an average diameter of 600-800 nm, which is made up of some
      nanopricks with an average length of 100-200 nm. These products are characterized
      by means of scanning electron microscopy (SEM), X-ray diffraction (XRD) and
      transmission electronic microscopy (TEM). It is found that the BSA and ascorbic
      acid (AA) have great effects on the morphology of the resulting products. Two
      different growth mechanisms are proposed. The study on surface enhanced Raman
      scattering (SERS) activities is also carried out between Au microspheres and Au
      sea urchin-like architectures. It is found that Au urchin-like architectures
      possess much higher SERS activity than the Au microspheres. Our work may shed
      light on the design and synthesis of hierarchically self-assembled 3D micro/nano
      architectures for SERS, catalysis and biosensors.

PMID- 23138656
TI  - [Extended spectrum beta lactamase forming pathogens (ESBL)].

PMID- 23138658
TI  - [Ventilation strategies for chronic obstructive pulmonary disease].
AB  - Chronic obstructive pulmonary disease (COPD) is considered to be one of the most
      frequent pulmonary diseases in industrialized countries. Non-invasive ventilation
      (NIV) is the first choice therapy in acute exacerbations of chronic hypercapnic
      respiratory failure (AE-COPD). Effective delivery of NIV requires a specialized
      interdisciplinary team with sufficient monitoring. NIV is delivered as assisted
      positive pressure ventilation where high inspiratory flow and peak pressure are
      required. The external positive end expiratory pressure (PEEP) should be adjusted
      to the intrinsic PEEP. Criteria of success are improvement in the clinical,
      especially neurological condition as well as improvement of pH and PaCO(2).
      Patients with a pH between 7.25 and 7.35 have demonstrated most benefit from NIV.
      In cases of patients not responding to NIV endotracheal intubation should be
      initiated in a timely manner. Assisted ventilation modes are preferred over
      controlled ventilation modes in intubated COPD patients. Settings of respirators
      have to be aimed at a reduction of intrinsic PEEP and dynamic hyperinflation.
      This includes sufficient external PEEP, long expiration times and low respiratory
      frequencies even allowing for permissive hypercapnia.

PMID- 23138659
TI  - Aetiology of acquired 'drop foot' deformity in Malawian children: a case series
      of 50 patients.
AB  - The objective of our study was to investigate the clinical presentation of
      patients with acquired foot drop in Malawi; the association of intramuscular
      injections and quinine administration; and the association between private sector
      clinics. A consecutive case series of 50 paediatric patients with foot drop was
      identified that represented 5% of all outpatient appointments during the study
      period. Ninety percent of all patients had received a gluteal intramuscular
      injection of quinine, of which 58% were treated in private clinics. This study
      presents the first description of the aetiology of acquired foot drop in Malawi
      and suggests that gluteal intramuscular injection of quinine is the leading
      cause.

PMID- 23138660
TI  - A rare case of diffuse cutaneous leishmaniasis in an immunocompetent patient from
      sub-Himalayan India.
AB  - Diffuse cutaneous leishmaniasis (DCL) is a rare variant of cutaneous
      leishmaniasis (CL) characterised by multiple (>=10), widespread, slowly
      progressive, cosmetically disfiguring, non-ulcerating nodules without visceral
      involvement. The disease is resistant to chemotherapy and characterized by
      relapses. We present a rare case of a patient with DCL who had extensive lesions
      (282) and who was HIV negative from a new focus of leishmaniasis in sub-Himalayan
      India. A favourable response with a regression of the lesions was observed after
      a month of treatment with intravenous and intralesional sodium stibogluconate
      with oral pentoxiphyline. Familiarity with such exceptional cases in
      immunocompetent individuals may facilitate diagnosis and a promising treatment
      outcome.

PMID- 23138661
TI  - Bacterial sensor kinases using Fe-S cluster binding PAS or GAF domains for O2
      sensing.
AB  - [4Fe-4S](2+) clusters are used by very diverse types of bacterial sensors for
      response to oxygen, including DNA-binding proteins of the CRP/FNR family and
      sensor kinases like NreB. In NreB the cluster is bound by an input domain of the
      PAS type. The [4Fe-4S](2+) cluster of NreB responds to O(2) by degradation to a
      [2Fe-2S](2+) cluster which is labile and decomposes. NreB constitutes together
      with AirS the NreB/AirS family of bacterial sensor kinases that contain PAS or
      GAF domains for binding of [4Fe-4S](2+) or [2Fe-2S](2+) clusters and oxygen
      sensing. The NreB/AirS family is related to the FixL sensor kinases that use
      hemeB binding PAS domains for oxygen sensing.

PMID- 23138662
TI  - The one-nail brown band: macro- and micro-morphology.

PMID- 23138663
TI  - Idiopathic macular telangiectasia type 2: ?the progressive vasculopathy.
AB  - Purpose. To describe the complete sequence of the progressive vasculopathy in
      macular telangiectasia type 2.?Methods. This is a report of a case demonstrating
      the complete vasogenic sequence in macular telangiectasia type 2 over the course
      of 15 years, and representative images from a collective of 150 patients with
      macular telangiectasia type 2 employing fundus photography, fluorescein
      angiography, and optical coherence tomography.?Results. Macular telangiectasia
      may progress along a predictable vasogenic sequence which consists of
      nonproliferative stages, characterized by temporal loss of macular luteopigment
      and inner retinal volume loss in the absence of vascular changes, followed by a
      progressive proliferative vasculopathy, first involving the deep capillary plexus
      with eventual extension of the vascular changes circumferentially in the inner
      retinal capillary plexus. Late proliferative stages may become indistinguishable
      from advanced neovascular age-related macular degeneration.?Conclusions. While it
      is rare to observe the complete vasogenic sequence of macular telangiectasia type
      2, a classification into nonproliferative and proliferative stages can be
      established, and may prove helpful as the mechanisms driving the pathogenic
      process through those stages are identified.

PMID- 23138664
TI  - Cataracts and Dupuytren disease: a case report and review of the literature.
AB  - Purpose. Dupuytren disease is an inherited proliferative and progressive
      connective disease. Ectopic disease may, however, be located distant from the
      palmar fascia. ?Methods. Case report and review of the literature. ?Results. We
      describe a case of symmetric bilateral posterior subcapsular cataracts associated
      with symmetric bilateral Dupuytren disease and symmetric bilateral Ledderhose
      disease in a 56-year-old Caucasian man. His medical history was negative for
      glucocorticoids intake, diabetes, and exposure to radiation. Serum transforming
      growth factor beta (TGF-beta)1 concentration has been evaluated and was found to
      be almost double compared to the controls. ?Conclusions. We speculate that the
      TGF-beta plays an important role for ocular and connective tissue disorders.

PMID- 23138665
TI  - Mixture of ether and silicone oil for the treatment of inferior complicated
      retinal detachment.
AB  - PURPOSE: To report the efficacy and ocular tolerance of a new tamponade made with
      ether and silicone oil (HeavySil [HSIL]) for the treatment of retinal detachment
      (RD) complicated by inferior proliferative vitreous retinopathy (PVR). METHODS:
      Prospective noncomparative interventional study on 31 consecutive eyes that
      underwent pars plana vitrectomy and were treated with HSIL as an intraocular
      tamponade. All patients presented with at least one retinal break and grade B-C
      PVR located between 4 and 8 o'clock. The main endpoint criteria were retinal
      reattachment after the removal of HSIL and complications arisen from the use of
      this tamponade. RESULTS: Primary anatomic success was achieved in 27 out of 31
      cases. Mean visual acuity improved from logMAR 1.4 (SD 0.7) to logMAR 1.1 (SD
      0.6) (p=0.02). The main complications reported were cataract formation (5 out of
      7 phakic eyes cases), clinically visible emulsification (6 cases), and difficulty
      of oil removal in 3 cases. Severe intraocular inflammation with HSIL in situ was
      found in only one case. CONCLUSIONS: HeavySil, a saturated solution of ether with
      silicone oil, is a safe and effective tamponade agent for the treatment of
      complicated RD. The most common complications are cataract formation and oil
      emulsification.

PMID- 23138666
TI  - The assimilation of evidence-based healthcare innovations: a management-based
      perspective.
AB  - In order to reap the benefits of the nation's vast investments in healthcare
      discoveries, evidence-based healthcare innovations (EBHI) must be assimilated by
      the organizations that adopt them. Data from a naturalistic field study are used
      to test a management-based model of implementation success which hypothesizes
      strategic fit, climate for EBHI implementation, and fidelity will explain
      variability in the assimilation of EBHIs by organizations that adopted them under
      ordinary circumstances approximately 6 years earlier. Data gathered from top
      managers and external consultants directly involved with these long-term EBHI
      implementation efforts provide preliminary support for predicted positive
      linkages between strategic fit and climate; climate and fidelity; and fidelity
      and assimilation. Mediated regression analyses also suggest that climate and
      fidelity may be important mediators. Findings raise important questions about the
      meaning of assimilation, top managers' roles as agents of assimilation, and the
      extent to which results represent real-world versus implicit models of
      assimilation.

PMID- 23138667
TI  - Corneal thickness and volume in subclinical and clinical keratoconus.
AB  - To evaluate corneal thickness and volume in subclinical and clinical keratoconus
      in Asian population with the aim of discriminating between normal and ectatic
      cornea. Eyes were placed into one of the following three groups: normal,
      subclinical, and mild-moderate keratoconus. Pentacam Scheimpflug imaging (Oculus
      Inc., Wetzlar, Germany) was performed for each participant to record thinnest
      corneal thickness, central corneal thickness, corneal volume (CV), peripheral
      corneal thickness (PCT) and percentage thickness increase (PTI) at 2, 4, 6, and 8
      mm. The data were exported to SPSS for statistical analysis. Subjects comprised
      52 normal, 15 subclinical keratoconus, and 32 mild-moderate clinical keratoconus
      eyes. Our results indicated that corneal thickness (CT) distribution, PTI, and CV
      in normal eyes were significantly different compared with subclinical and
      clinical keratoconus (P < .05). Overall, subclinical group exhibited lower CT
      distribution and volume, and higher PTI in comparison with normal eyes. However,
      they showed higher CT distribution and volume, and lower PTI compared with
      keratoconus group. In addition, there was a smaller change in PCT and PTI from
      the thinnest point of the cornea to the periphery. The results of the present
      study indicate that CT parameters and CV were significantly different in normal
      versus subclinical group and in normal versus keratoconus group. These findings
      could help clinicians to better discriminate between normal and ectatic cornea.

PMID- 23138668
TI  - ST-Elevation myocardial infarction network: systematization in 205 cases reduced
      clinical events in the public health care system.
AB  - BACKGROUND: The major cause of death in the city of Sao Paulo (SP) is cardiac
      events. At its periphery, in-hospital mortality in acute myocardial infarction is
      estimated to range between 15% and 20% due to difficulties inherent in large
      metropoles. OBJECTIVE: To describe in-hospital mortality in ST-segment elevation
      acute myocardial infarction (STEMI) of patients admitted via ambulance or
      peripheral hospitals, which are part of a structured training network (STEMI
      Network). METHODS: Health care teams of four emergency services (Ermelino
      Matarazzo, Campo Limpo, Tatuape and Saboya) of the periphery of the city of Sao
      Paulo and advanced ambulances of the Emergency Mobile Health Care Service
      (abbreviation in Portuguese, SAMU) were trained to use tenecteplase or to refer
      for primary angioplasty. A central office for electrocardiogram reading was used.
      After thrombolysis, the patient was sent to a tertiary reference hospital to
      undergo cardiac catheterization immediately (in case of failed thrombolysis) or
      in 6 to 24 hours, if the patient was stable. Quantitative and qualitative
      variables were assessed by use of uni- and multivariate analysis. RESULTS: From
      January 2010 to June 2011, 205 consecutive patients used the STEMI Network, and
      the findings were as follows: 87 anterior wall infarctions; 11 left bundle-branch
      blocks; 14 complete atrioventricular blocks; and 14 resuscitations after initial
      cardiorespiratory arrest. In-hospital mortality was 6.8% (14 patients), most of
      which due to cardiogenic shock, one hemorrhagic cerebrovascular accident, and one
      bleeding. CONCLUSION: The organization in the public health care system of a
      network for the treatment of STEMI, involving diagnosis, reperfusion, immediate
      transfer, and tertiary reference hospital, resulted in immediate improvement of
      STEMI outcomes.

PMID- 23138669
TI  - Study of breathing pattern and thoracoabdominal movement in mitral valve disease.
AB  - BACKGROUND: patients with mitral valve disease can progress to having pulmonary
      congestion, which increases the work the respiratory muscles. This overload can
      change the breathing pattern with a predominance of rib cage displacement or
      presence of paradoxical movements. OBJECTIVE: a) to study the breathing pattern
      and thoracoabdominal movement of patients with mitral valve disease; b) to study
      the effect of body position on breathing parameters; and c) to correlate
      pulmonary hypertension with lack of coordination of thoracoabdominal movement.
      METHODS: the breathing pattern and thoracoabdominal movement of patients with
      mitral valve disease were assessed using respiratory inductive plethysmography
      during quiet breathing in the dorsal decubitus and sitting positions for two
      minutes. The variables assessed were tidal volume, breathing time and
      thoracoabdominal movement. RESULTS: of the 65 patients selected, 10 were
      excluded, 29 were in the mitral stenosis group and 26 in the mitral regurgitation
      group. Tidal volume, pulmonary ventilation and mean inspiratory flow
      significantly increased in the sitting position, with no difference between the
      groups. The thoracoabdominal movement remained coordinated in all groups and
      positions; except for five patients in the dorsal decubitus position, who lacked
      coordination (three in the mitral stenosis group; two in the mitral regurgitation
      group). A significant correlation with pulmonary artery pressure values was
      observed (r = 0.992; p = 0.007). CONCLUSION: No difference in breathing pattern
      or thoracoabdominal movement was found between patients with mitral stenosis and
      regurgitation. The sitting position increased tidal volume without altering
      breathing times. The lack of coordination of the thoracoabdominal movement in the
      dorsal decubitus position was associated with pulmonary hypertension.

PMID- 23138670
TI  - Role of echocardiography in the ventricular assessment of the transplanted heart
      versus heart rejection.
AB  - BACKGROUND: Heart transplantation is an alternative for individuals with end
      stage heart disease. However, episodes of heart rejection (HR) are frequent and
      increase morbidity and mortality, requiring the use of an accurate non-invasive
      exam for their diagnosis, since endomyocardial biopsy (EMB) is not a complication
      free procedure. OBJECTIVE: To compare the parameters obtained by use of Doppler
      echocardiography in a group of transplanted patients with HR (TX1) and another
      group of transplanted patients without rejection (TX0), having as reference a
      control group (CG) and observing the behavior of the left ventricular systo
      diastolic function expressed as the myocardial performance index (MPI) METHODS:
      Transthoracic echocardiographies were performed from January 2006 to January 2008
      to prospectively assess 47 patients divided into three groups: CG (36.2%); TX0
      (38.3%); and TX1 (25.5%). The MPI was compared between the groups, and data were
      analyzed by use of Fisher exact test and nonparametric Kruskal-Wallis test, both
      with significance level of 5%. RESULTS: The groups did not differ regarding age,
      weight, height, and body surface. When compared to GC, TX0 and TX1 showed a
      change in the left ventricular systo-diastolic function, expressed as an increase
      in MPI, which was greater in TX1 [0.38 (0.29 - 0.44); 0.47 (0.43 - 0.56); 0.58
      (0.52 - 0.74), respectively; p < 0.001]. CONCLUSION: Echocardiography was a very
      accurate test to detect changes in the systo-diastolic function of the
      transplanted heart; however, it did not prove to be reliable to replace BEM in
      the safe diagnosis of HR.

PMID- 23138671
TI  - Acute myocardial infarction after noncardiac surgery.
AB  - Over 230 million surgeries are performed annually worldwide, cardiac
      complications being the most common causes of postoperative morbidity and
      mortality. As life expectancy has extended worldwide, a growing number of
      patients with multiple comorbidities have undergone noncardiac surgeries.
      Consequently, cardiovascular complications associated with those procedures are
      expected to increase, and perioperative acute myocardial infarction (AMI) might
      become a frequent problem. In Brazil, the number of noncardiac surgical
      procedures has also increased, and approximately three million surgeries are
      performed annually. Despite advances in surgical and anesthetic techniques,
      mortality and costs related to those procedures have also increased, thus,
      requiring the development of strategies to reduce mortality(4). The occurrence of
      perioperative AMI prolongs the need for intensive care and the hospital length of
      stay, increases the cost of hospitalization, and reduces long-term survival. This
      literature review approaches the pathophysiology, incidence, diagnosis and
      treatment of perioperative AMI based on current evidence.

PMID- 23138672
TI  - Imaging of postpartum coronary artery's spontaneous dissection treated with
      stents implantation.

PMID- 23138673
TI  - Estimation of left atrial blood stasis using diastolic late mitral annular
      velocity.
AB  - AIMS: Diastolic late mitral annular velocity (a') measured by transthoracic
      echocardiography (TTE) is reported to represent left atrial (LA) pump function
      and the severity of LA remodelling. The purpose of this study is to investigate
      the association between a' and LA blood stasis in patients with non-valvular
      paroxysmal atrial fibrillation. METHODS AND RESULTS: We enrolled 138 consecutive
      patients with non-valvular paroxysmal atrial fibrillation who had spontaneous
      sinus rhythm at the time of echocardiography. Using TTE, a' was determined as an
      average of tissue Doppler velocities measured at septal and lateral mitral
      annuli. Transoesophageal echocardiography was also performed on the same day as
      TTE, and spontaneous echo contrast (SEC) and LA appendage flow velocity were
      examined. Spontaneous echo contrast was observed in 21 (15%) patients. Patients
      in the lowest quartile of a' (<=6.4 cm/s) demonstrated SEC more frequently (44
      vs. 6%, P < 0.0001) and had lower LA appendage flow velocity (39 +/- 13 vs. 53 +/
      16 cm/s, P < 0.0001) than those in the other quartiles. Receiver-operating
      characteristic curve analysis showed that the best cut-off value of a' was 7.0
      cm/s for the prediction of SEC with a sensitivity of 80%, specificity of 81%, and
      predictive accuracy of 80%. Multivariate analysis revealed that decreased a' (OR
      = 0.61, P = 0.0026) was independently associated with SEC. CONCLUSION: Decreased
      a' may be a useful parameter for the estimation of LA blood stasis in patients
      with paroxysmal atrial fibrillation.

PMID- 23138674
TI  - Fabrication of unique hollow silicate nanoparticles with hierarchically
      micro/mesoporous shell structure by a simple double template approach.
AB  - An innovative type of hollow silicate nanoparticle with a micro/mesoporous shell
      wall (NSHPMS) was synthesized at room temperature via an eco-friendly double
      template approach, followed by simple acid reflux. TEM observations of NSHPMSs
      showed hollow interior nanoparticles (<100 nm) with a wormhole-like shell
      structure. The nitrogen gas (N(2)) adsorption/desorption isotherm exhibited a
      unique two-step pattern: the first step (0.2 < P/P(o) < 0.35) signifies the
      presence of the micro/mesoporous shell wall while the second step (0.85 < P/P(o)
      < 0.99) represents the void space in between the NSHPMSs. This resulted to an
      improved specific surface area up to ~2055.5 m(2) g(-1) and a total pore volume
      as high as ~6.59 cm(3) g(-1) which is better compared with the usual reported
      data for hollow particles with a mesoporous shell wall. The stable wormhole
      mesoporous shell wall provided sufficient spaces that contribute to high
      adsorption capacities and faster adsorption rates. One can envision that larger
      quantities of framework composition can be obtained using our NSHPMSs.

PMID- 23138675
TI  - A cross-sectional study comparing strength profile of dorsal and palmar flexor
      muscles of the wrist in epicondylitis and healthy men.
AB  - BACKGROUND: Strength training has been proposed by several authors to treat
      Lateral Epicondylitis. However, there is still a lack of information concerning
      muscle weakness and its relationship to imbalances and fatigability of forearm
      muscles during dynamic conditions in subjects after epicondylitis recovery. AIM:
      To analyze the relationship between lateral humeral epicondylitis, and forearm
      muscle strength and fatigue. SETTING: Rehabilitation specialized center
      POPULATION: Cross-sectional study in eight former epicondylitis men free of
      symptoms and actively working at the moment of the evaluation and eight healthy
      men volunteers. METHODS: Isokinetic tests were performed at different velocities
      in order to assess strength in concentric and eccentric contractions.
      Additionally, a long-term concentric test was carried out in order to analyze
      strength during endurance. The following variables were analyzed: Average torque
      of dorsal and palmar flexors of the wrist and ratio of agonist/antagonist for non
      endurance contractions; length of initial and final plateaus and the slope of
      average torque decay during the endurance test. RESULTS: In both groups, average
      torque produced by palmar flexor muscles was higher than that produced by dorsal
      flexor muscles. Patients showed higher strength in palmar flexor muscles, whereas
      dorsal flexor strength was similar for both populations. Palmar flexor vs. dorsal
      flexor ratio was significantly higher in patients for eccentric contractions.
      Regarding fatigue, results showed that torque decreased earlier in patients.
      CONCLUSIONS AND CLINICAL REHABILITATION IMPACT: Both palmar flexor force and
      palmar/dorsal ratio in eccentric exercise were significantly higher in patients.
      This finding indicates a muscular imbalance in patients underlying the
      epicondylitis condition. Additionally, former patients fatigued earlier. Findings
      indicate that muscle imbalances and fatigability might be related to lateral
      epicondylitis. This information may be useful in the design and monitoring of
      programs intended for lateral epicondylitis rehabilitation. More studies are
      necessary to conclude if these differences are cause or consequence of the
      epicondylitis.

PMID- 23138676
TI  - Psychiatric disorders in patients suffering from an acute cerebrovascular
      accident or traumatic injury, and their effects on rehabilitation: an
      observational study.
AB  - BACKGROUND: The presence of a post-traumatic psychiatric disorder in patients
      with acute injuries may have adverse effects on outcomes. AIM: In this study our
      aims were: (1) to assess the frequency of psychiatric disorders after a
      cerebrovascular accident or traumatic injury requiring rehabilitation; (2) to
      examine whether there was any correlation between psychiatric disorders and
      patients' baseline demographic and clinical variables. DESIGN: The study
      consisted of two phases: the first was cross-sectional and the second prospective
      with a 12-month follow-up. The period of recruitment was two years. The results
      of the first phase are presented here. SETTING: The study sample consisted of a
      consecutive series of patients admitted to hospital because of an acute
      cerebrovascular accident or a traumatic injury and referred for a rehabilitation
      program. Two inpatient Rehabilitation Hospitals were involved in the study.
      POPULATION: The sample consisted of 230 consecutive patients with a recent
      cerebrovascular accident or trauma included in a rehabilitation program. METHODS:
      The sample included: 89 men (39%) and 141 women (61%) aged 20-97 years.
      Psychiatric disorders and motor disabilities were assessed through psychiatric
      interview and the mini-international neuropsychiatric interview plus (MINI Plus)
      and, respectively, with the functional independent measure (FIM). In case of post
      traumatic stress disorder (PTSD), severity was assessed through the Davidson's
      Trauma scale. Psychiatric disorders were correlated to demographic and clinical
      variables through univariate and multivariate analyses, the latter with logistic
      regression models. RESULTS: The most frequent entry diagnoses were traumatic
      fracture (41.3%) and stroke (37.0%). Ninety-three patients (40.4%) had one or
      more psychiatric disturbances at study entry, the commonest being depression (56
      cases, 24.7%) and anxiety (23 cases, 10.0%). PTSD was present in 8 cases (3.5%).
      A history of psychiatric disorder was reported by 55 patients (24.2%) Compared to
      the rest of the study population, these subjects had more psychopathologic
      complaints (P<0.001). Mean total FIM score was 54.4 (SD=17.8) and 61.2 (SD=19.6)
      in patients with and without psychopathology (P<0.01) Independent predictors of
      psychopathology included past psychiatric history, lower total FIM scores, and
      limb amputation. Depression was predicted by history of psychiatric disorders and
      lack of partner. CONCLUSION: History of psychiatric disorders is the most
      relevant factor associated with psychopathology in patients with an acute
      cerebrovascular accident or traumatic injury, followed by lower total FIM scores,
      and type of pathologic event. CLINICAL REHABILITATION IMPACT: The presence of
      psychiatric disorders may potentially influence the rehabilitation process and
      outcomes; thus their recognition and management are key factors during a
      rehabilitation program.

PMID- 23138677
TI  - Is walking in daily life a moderate intensity activity in patients with chronic
      obstructive pulmonary disease?
AB  - BACKGROUND: So far there are no studies investigating whether the time spent
      walking in daily life by patients with COPD corresponds to an activity of at
      least moderate intensity according to the recommendations of the American College
      of Sports Medicine (ACSM). AIM: To quantify in patients with COPD the time
      spent/day in physical activity of at least moderate intensity according to the
      ACSM (TPA>moderate); and to compare their TPA>moderate with the total time spent
      walking/day in daily life (TW). DESIGN: Cross-sectional study. SETTING: Patients
      entering in a pulmonary rehabilitation program at a University Hospital in
      Brazil. POPULATION: Seventy-three patients with COPD (FEV1 40+/-15% pred; 65+/-9
      years). METHODS: TW and TPA>moderate were respectively assessed with the DynaPort
      and SenseWear activity monitors for 12 hours/day during 2 days. RESULTS: There
      was significant difference between TW and TPA>moderate (53 [36-80] versus 12 [3
      33] minutes/day, respectively; P<0.0001). Although 84% of patients reached more
      than 30 minutes/day of TW, only 29% reached more than 30 minutes/day of
      TPA>moderate. TPA>moderate correlated modestly with TW (r= 0.52; P<0.0001).
      CONCLUSION: The majority of patients with moderate-very severe COPD walk more
      than 30 minutes/day; however this does not mean that they are physically active,
      since less than 1/4 of their time spent walking can be considered as moderate
      intensity activity. CLINICAL REHABILITATION IMPACT: Moderate-intensity physical
      activity in patients with COPD is more reduced than previously known. There is a
      clear need to increase their daily physical activity and lead a higher proportion
      of this population to comply with the minimum recommendations.

PMID- 23138678
TI  - Playing-related musculoskeletal disorders in music students-associated
      musculoskeletal signs.
AB  - BACKGROUND: Pain and overuse are common problems for musicians. Up to 80% of
      professional musicians suffer from playing-related musculoskeletal disorders
      (PRMD). The prevalence rate in music students is very high as well. Sufficient
      data on the underlying musculoskeletal dysfunctions however is scarce.
      Additionally, the self-assessment of health in musicians seems to differ compared
      to non-musicians, which might influence their attitudes concerning preventive
      strategies. AIM: Evaluation of frequency of PRMD in music students, investigation
      of signs and symptoms in music students compared to non-music controls,
      comparison of self-reported health and well-being between the two groups. DESIGN:
      Prospective, cross-sectional, case control, non-randomized. SETTING: Other
      (University volunteers). POPULATION: Music students in comparison to a non-music
      control group. METHOD: Musculoskeletal examination and questionnaire of 36
      volunteers of a music university and 19 volunteer students of an university of
      education were analyzed. The total number of musculoskeletal dysfunctions and
      differences between the student groups were examined. The personal pain and
      health self-rating were compared between music and non-music students. RESULTS:
      Eighty one percent of musicians experienced PRMD. Musicians experienced 6.19 pain
      regions on average compared to 4.31 of non-musicians. Musicians experiencing PRMD
      reported significantly (P<0.05) more pain locations than musicians without. Music
      students presented with nearly the double amount (8.39 versus 4.37) of
      musculoskeletal dysfunctions per person compared to the non-music control group.
      Nevertheless, musicians significantly (P<0.05) rated their health more positively
      than the controls. CONCLUSION: Musicians presented with more pain regions and a
      higher amount of musculoskeletal dysfunctions. Further studies evaluating the
      clinical relevance and their role in the development of PRMD are warranted.
      CLINICAL REHABILITATION IMPACT: Screening of musicians for musculoskeletal
      dysfunction may identify those musicians at increased risk. Early treatment may
      prevent PRMD in musicians. Additional research is needed to confirm our
      hypothesis.

PMID- 23138679
TI  - Balance and walking involvement in facioscapulohumeral dystrophy: a pilot study
      on the effects of custom lower limb orthoses.
AB  - BACKGROUND: Autosomal dominant facioscapulohumeral dystrophy (FSHD), the third
      most common muscular dystrophy, is characterised by asymmetric and highly
      variable muscle weakness. In FSHD patients, the coupling of the ankle muscles
      impairment with the knee, hip and abdominal muscles impairment, causes complex
      alterations of balance and walking with deterioration of quality of life (QoL).
      AIM: The aim of this pilot study is to evaluate the effects of custom orthoses
      (foot orthosis-FO and ankle foot orthosis-AFO) on balance, walking and QoL of
      FSHD patients through a multidimensional approach. DESIGN: Pilot study. SETTING:
      Outpatient Rehabilitation Department of Don Gnocchi Foundation. POPULATION:
      Fifteen patients with facioscapulohumeral muscular dystrophy were studied.
      METHODS: On 15 FSHD patients clinical evaluation (Manual Muscle Test-MMT,
      Clinical Severity Score), performance tests (10 meter Walking test-10mWT and 2
      minute Walking Test-2minWT), instrumental assessment (stabilometric evaluation),
      disability (Rivermead Mobility Index- RMI, Berg Balance Scale-BBS) and patient
      oriented (Medical Outcome Study 36-item Short Form-SF-36, North American Spine
      Society-NASS and Visual Analogue Scale-VAS) measures were performed. Patients
      were evaluated first, wearing their shoes and then wearing their shoes plus
      orthoses. This evaluation was performed 1 month after wearing the orthoses.
      RESULTS: The shoes plus orthoses evaluation, performed after one month in which
      the patients daily wore the custom lower limb orthoses, showed a significant
      improvement of walking performance (10-mWT p<0.01), balance (Romberg Index
      p<0.05; Medio-Lateral Velocity p<0.05) and QoL (PCS p<0.01). CONCLUSION: This
      pilot study shows that in FSHD patients' custom lower limb orthoses (foot
      orthoses and ankle-foot-orthoses); evaluated by using a multidimensional
      approach, improve walking, balance and QoL. CLINICAL REHABILITATION IMPACT: These
      preliminary results suggest that custom lower limb orthoses could reduce the risk
      of falling with a positive effect on our patients' safety. Our results should
      encourage the scientific community to do efficacy study on this hot topic.

PMID- 23138680
TI  - Safety and tolerability of duloxetine in elderly patients with major depressive
      disorder:  a pooled analysis of two placebo-controlled studies.
AB  - The objective of this study was to examine the safety and tolerability of
      duloxetine hydrochloride, a serotonin-norepinephrine reuptake inhibitor, in a
      large cohort of elderly patients with major depressive disorder. Data were pooled
      from 8-week and 12-week, double-blind, randomized, placebo-controlled trials of
      duloxetine 60 mg/day (duloxetine=456; placebo=225). Discontinuation rates because
      of adverse events, treatment-emergent adverse events, abnormal changes in vital
      signs and weight, and changes in laboratory analytes were compared between
      treatments using a Cochran-Mantel-Haenszel test. Changes in laboratory analytes
      were analyzed using an analysis of variance model. Adverse event-related
      discontinuation rates were not significantly different between duloxetine and
      placebo (10.7 vs. 7.1%; P=0.13). Treatment-emergent adverse events for duloxetine
      of at least 5% and twice the rate of placebo were dry mouth, constipation,
      nausea, diarrhea, dizziness, and fatigue. Abnormal changes in vital signs and
      weight were not significantly different at any time between duloxetine and
      placebo. The mean changes in platelet count, alkaline phosphatase, potassium,
      random glucose, uric acid, and cholesterol were significantly different between
      duloxetine and placebo (P<0.05), but none of these differences were considered
      clinically relevant. The incidence of abnormal low sodium levels was not
      significantly different between treatments. These safety results may better
      inform clinicians providing individualized care to elderly patients with major
      depressive disorder.

PMID- 23138685
TI  - Pharyngeal enterogenous cyst associated with canalis basilaris medianus in a
      newborn.
AB  - We report the CT and MR characteristics of a newborn with a rare, complex
      malformation characterised by a large rhinopharyngeal and oropharyngeal
      enterogenous cyst, associated with an osseous defect of the basiocciput, called
      canalis basilaris medianus (CBM). A partial herniation of the bulb was
      demonstrated through the bony defect on the midline. The enterogenous cyst
      occupied the rhinopharynx and oropharynx, narrowing the pharyngeal lumen and
      making it difficult for the introduction of an orotracheal tube.

PMID- 23138686
TI  - Intramolecular frustrated lewis pairs: formation and chemical features.
AB  - Intramolecular vicinal and geminal frustrated Lewis pairs (FLPs) featuring bulky
      substituents at phosphorus or nitrogen and strongly electron-withdrawing bulky
      pentafluorophenyl substituents at boron undergo a variety of addition and/or
      activation reactions with small molecules. A number of examples of such reactions
      are presented and discussed, among them the FLP activation of dihydrogen to give
      zwitterionic phosphonium (or ammonium)/hydridoborate zwitterions. Intramolecular
      FLPs also add to organic carbonyl compounds (including carbon dioxide), to
      alkenes and alkynes (including conjugated dienes, diynes or enynes), to
      heterocumulenes, to azides, and to nitric oxide.

PMID- 23138682
TI  - Hyperreflective dots surrounding the central retinal artery and vein in optic
      disc melanocytoma revealed by spectral domain optical coherence tomography.
AB  - PURPOSE: To report findings of optic disc melanocytoma (ODM) obtained using
      spectral domain optical coherence tomography (SD OCT), with special reference to
      the central retinal artery and vein surrounded by hyperreflective dots. METHODS:
      Retrospective review of five eyes of five patients with ODM. Demographic
      information, ophthalmic examination including best-corrected visual acuity,
      dilated funduscopic examination, and SD OCT images were evaluated. RESULTS: Dome
      shaped, darkly pigmented tumors were seen ophthalmoscopically in the optic discs
      of all eyes. On OCT, the first branches of the central retinal artery and/or vein
      were well defined as oblique sections of tubular structures with a perivascular
      distribution of hyperreflective dots in the elevated retina (nerve fiber layer)
      over the tumor. The portions where these vessels turn toward the retina were
      displaced more anteriorly than those of eyes without ODM. Hyperreflective dots of
      various sizes were also observed in elevated retinas over the tumors, which
      shadowed and obscured the subjacent tissue in all eyes. CONCLUSIONS: SD OCT
      provides higher definition images of ODM relating to the branches of the central
      retinal artery/vein, revealing anterior displacement of vessels and perivascular
      distribution of hyperreflective dots that suggest melanophages and/or tumor cells
      or proteins and/or lipid deposits.

PMID- 23138687
TI  - Carbon-based frustrated Lewis pairs.
AB  - The use of FLPs offers a new and versatile strategy to activate small molecules
      such as H2, CO2, acetylenes, disulfides, olefins, and nitrogen oxides. This
      chapter describes the recent advances reported on the design and reactivity of
      new frustrated systems constituted by at least one carbon-based partner.

PMID- 23138681
TI  - Test-retest variability in structural parameters measured with glaucoma imaging
      devices.
AB  - In addition to classical stereo-disc photography, various glaucoma imaging
      devices were developed in the last two decades to quantitatively measure and
      record glaucoma-related structural parameters of the eye. In determining whether
      or not the glaucomatous damage progressed from baseline and in estimating the
      number of test results' optimal frequency needed to confirm disease progression,
      information relating to the test-retest variability of measurement results
      provided by each imaging device is indispensable. Such information enables the
      clinician to apply these devices in practice. The test-retest variability of a
      system is usually estimated using the Bland-Altman analysis and by calculating
      the coefficient of variation (CV), intraclass correlation coefficient (ICC), and
      minimum detectable changes (MDC). The reported CV, ICC, and MDC values for
      glaucoma-related structural parameter measurement results of stereo-disc
      photographs, confocal scanning laser ophthalmoscopes, scanning laser
      polarimeters, time-domain optical coherence tomography (OCT), spectral-domain OCT
      (SD-OCT), anterior-segment OCT, and ultrasound biomicroscope are systematically
      reviewed in this manuscript, which will enable the clinician to interpret
      measurement results provided by each glaucoma imaging devices and thus be useful
      in practice. Although SD-OCT systems may be currently prevailing because of the
      volume of information provided and the relatively better test-retest variability,
      these systems need improvement in their test-retest variability measurement
      capabilities.

PMID- 23138688
TI  - Solid-state NMR as a spectroscopic tool for characterizing phosphane-borane
      frustrated lewis pairs.
AB  - Frustrated Lewis pair (FLP) chemistry has provided a new strategy for small
      molecule binding and/or catalytic activation. It is based on the cooperative
      reaction behavior of Lewis acid and Lewis base centers that are in close
      proximity to each other (e.g., within the same molecule) but cannot form a direct
      bond because of geometrical constraints. The most prominent FLPs are based on
      intramolecular phosphane-borane adducts, whose catalytic properties can be
      tailored over wide ranges of reactivity and selectivity. For the structural and
      chemical design of such systems, a fundamental understanding needs to be
      developed on how structure, dynamics and covalent interactions between the Lewis
      centers influence the reactivity profile. Advanced solid-state nuclear magnetic
      resonance (NMR) spectroscopic techniques afford new opportunities for addressing
      this challenge. Following a general introduction into the fundamentals of NMR
      spectroscopy, this review discusses the different types of internal interactions 
      magnetic shielding, nuclear electric quadrupolar coupling, indirect spin-spin
      interactions, and "through-space" dipole-dipole couplings - influencing NMR
      spectra in the solid state. As discussed in detail, each type of interaction
      bears specific informational content with regard to structural issues in FLP
      chemistry. One of the most attractive features of solid-state NMR is the
      possibility of tailoring the effective Hamiltonian by manipulations in either
      physical space or spin space. Using such "decoupling" or "recoupling" techniques
      certain types of interactions can be selectively turned off for spectral
      simplification or turned on for selective evaluation. The present review
      summarizes the most important selective averaging techniques that have found
      applications in the characterization of FLPs. In a second step the interaction
      parameters need to be connected with structure and bonding information. As
      illustrated in this chapter, ab initio calculations using density functional
      theory (DFT) methods have become indispensable for this task. Based on this
      comprehensive strategy including advanced NMR methodology, computer simulations,
      and ab initio calculations, the present review illustrates the utility of (31)P
      and (11)B NMR chemical shifts, (11)B electric field gradient tensors, and (31)P
      (11)B indirect and direct dipole-dipole interactions for characterizing
      intramolecular borane-phosphane FLPs, illustrating the potential of this method
      to (1) quantify the extent of boron-phosphorus bonding interactions (and hence
      the "degree of frustration") and (2) reveal specific structural details (i.e.,
      boron-phosphorus distances and other local geometry aspects) relating to the
      catalytic activities of these exciting materials.

PMID- 23138689
TI  - Improving NMR and MRI sensitivity with parahydrogen.
AB  - Parahydrogen induced polarisation (PHIP) has wide utility in NMR and MRI as it
      can increase the sensitivity of both techniques. The transfer of spin order from
      parahydrogen to nuclei in the analyte leads to an increased magnetic response
      following interrogation by RF pulses. This spin transfer is catalysed by a
      homogeneous or heterogeneous catalyst. The increased magnetic response not only
      reduces the number of transients required to obtain the spectrum or image, but
      can also illuminate previously undetectable species present in solution. From its
      theoretical prediction to its experimental validation, PHIP has been applied in a
      range of different areas such as the structural analysis of complexes,
      understanding reaction mechanisms involving hydrogen and for the production of
      contrast agents for use in MRI. PHIP can also be readily combined with other
      techniques such as photochemistry which widens its field of applicability. In
      this review, we detail the properties of parahydrogen and the methods for its
      preparation and utilisation in homogeneous and heterogeneous based hydrogenation
      and non-hydrogenative reactions. Specific examples are explained for the
      application of PHIP in photochemical and hydroformylation reactions. Pulse
      sequences designed to be compatible with PHIP are described to exemplify how the
      increase in sensitivity can be increased even further by the interrogation of the
      magnetic states optimally. Finally, a section on the use of PHIP in the
      production of contrast agents suitable for MRI, and the monitoring of
      hydrogenation reactions using imaging techniques is discussed. 

PMID- 23138691
TI  - Toward systems metabolic engineering in cyanobacteria: opportunities and
      bottlenecks.
AB  - We recently assessed the metabolism of Synechocystis sp PCC6803 through a
      constraints-based reconstruction and analysis approach and identified its main
      metabolic properties. These include reduced metabolic robustness, in contrast to
      a high photosynthetic robustness driving the optimal autotrophic metabolism.
      Here, we address how these metabolic features affect biotechnological
      capabilities of this bacterium. The search for growth-coupled overproducer
      strains revealed that the carbon flux re-routing, but not the electron flux, is
      significantly more challenging under autotrophic conditions than under mixo- or
      heterotrophic conditions. We also found that the blocking of the light-driven
      metabolism was required for carbon flux re-routing under mixotrophic conditions.
      Overall, our analysis, which represents the first systematic evaluation of the
      biotechnological capabilities of a photosynthetic organism, paradoxically
      suggests that the light-driven metabolism itself and its unique metabolic
      features are the main bottlenecks in harnessing the biotechnological potential of
      Synechocystis.

PMID- 23138690
TI  - Stress-induced grey matter loss determined by MRI is primarily due to loss of
      dendrites and their synapses.
AB  - Stress, unaccompanied by signs of post-traumatic stress disorder, is known to
      decrease grey matter volume (GMV) in the anterior cingulate cortex (ACC) and
      hippocampus but not the amygdala in humans. We sought to determine if this was
      the case in stressed mice using high-resolution magnetic resonance imaging (MRI)
      and to identify the cellular constituents of the grey matter that quantitatively
      give rise to such changes. Stressed mice showed grey matter losses of 10 and 15 %
      in the ACC and hippocampus, respectively but not in the amygdala or the
      retrosplenial granular area (RSG). Concurrently, no changes in the number or
      volumes of the somas of neurons, astrocytes or oligodendrocytes were detected. A
      loss of synaptic spine density of up to 60 % occurred on different-order
      dendrites in the ACC and hippocampus (CA1) but not in the amygdala or RSG. The
      loss of spines was accompanied by decreases in cumulative dendritic length of
      neurons of over 40 % in the ACC and hippocampus (CA1) giving rise to decreases in
      volume of dendrites of 2.6 mm(3) for the former and 0.6 mm(3) for the latter,
      with no change in the amygdala or RSG. These values are similar to the MRI
      determined loss of GMV following stress of 3.0 and 0.8 mm(3) in ACC and
      hippocampus, respectively, with no changes in the amygdala or RSG. This
      quantitative study is the first to relate GMV changes in the cortex measured with
      MRI to volume changes in cellular constituents of the grey matter.

PMID- 23138692
TI  - Allosteric competitive inhibitors of the glucose-1-phosphate
      thymidylyltransferase (RmlA) from Pseudomonas aeruginosa.
AB  - Glucose-1-phosphate thymidylyltransferase (RmlA) catalyzes the condensation of
      glucose-1-phosphate (G1P) with deoxy-thymidine triphosphate (dTTP) to yield dTDP
      d-glucose and pyrophosphate. This is the first step in the l-rhamnose
      biosynthetic pathway. l-Rhamnose is an important component of the cell wall of
      many microorganisms, including Mycobacterium tuberculosis and Pseudomonas
      aeruginosa. Here we describe the first nanomolar inhibitors of P. aeruginosa
      RmlA. These thymine analogues were identified by high-throughput screening and
      subsequently optimized by a combination of protein crystallography, in silico
      screening, and synthetic chemistry. Some of the inhibitors show inhibitory
      activity against M. tuberculosis. The inhibitors do not bind at the active site
      of RmlA but bind at a second site remote from the active site. Despite this, the
      compounds act as competitive inhibitors of G1P but with high cooperativity. This
      novel behavior was probed by structural analysis, which suggests that the
      inhibitors work by preventing RmlA from undergoing the conformational change key
      to its ordered bi-bi mechanism.

PMID- 23138693
TI  - Operative vs conservative treatment of traumatic patellar dislocation: results of
      a prospective randomized controlled clinical trial.
AB  - INTRODUCTION: Patellar dislocation is a common knee injury with mainly lateral
      dislocations, leading to ruptures of the medial patellofemoral ligament in most
      of the cases. Even though several prognostic factors for patellofemoral
      instability have been identified so far, the appropriate therapy for patients
      with patellar dislocation remains a controversial issue. The purpose of this
      study was to compare the outcome after conservative or operative treatment in
      patients after first-time patellar dislocation. PATIENTS AND METHODS: This
      randomized controlled clinical trial was designed multicentric including patients
      from six German orthopaedic and trauma departments. Twenty patients with a mean
      age of 24.6 years with first-time traumatic patella dislocation were included and
      randomized into either a conservative arm or an operative arm. Plain X-ray images
      of the knee joint (a.p. and lateral view and tangential view of both patellae)
      were performed in all cases prior to therapy to exclude osteochondral fragments
      requiring refixation. An MRI was recommended, but not compulsory. Patients were
      consulted after 6, 12, and 24 months with a questionnaire including the criteria
      of the Kujala score, recurrent dislocation, and satisfaction. RESULTS: The mean
      Kujala score of the conservative vs operative treatment group was 78.6 vs 80.3
      after 6 months (p = 0.842), 79.9 vs 88.9 after 12 months (p = 0.165), and 81.3 vs
      87.5 after 24 months (p = 0.339). Redislocation rate after 24 months was 37.5 %
      in the conservative group and 16.7 % in the operative group (p = 0.347). Due to
      the small number of patients that could be included, no significant difference
      between the groups could be detected. We see a tendency towards better results
      after operative treatment. CONCLUSION: Our multicentric prospective randomized
      controlled trial revealed no significant difference between conservative and
      operative treatment for patients after first-time traumatic patellar dislocation.
      However, a tendency towards a better Kujala score and lower redislocation rates
      for patients with operative treatment was observed. The small number of patients
      is a limiting factor of the study, leading to results without statistical
      significance. A meta-analysis including other study's level I data is desirable
      for the future.

PMID- 23138694
TI  - Low uptake of the combined test in The Netherlands--which factors contribute?
AB  - OBJECTIVE: The aim of this study was to evaluate which of the following factors
      affect the uptake of the combined test (CT) in The Netherlands: women's socio
      demographic background, attitude towards Down syndrome, attitude towards
      termination of pregnancy, counseling process, reimbursement policy, and knowledge
      on the aim of the CT. METHODS: Cross-sectional survey in the Northwest (NW) and
      the Northeast (NE) region of The Netherlands. RESULTS: Analyses were based on 820
      questionnaires (73% response rate). Women from the NW region opted more often for
      the CT than women from the NE region (52.1% and 16.5%, respectively, p < 0.001).
      Women of 36 years and older opted more often for the CT than younger women (59.4%
      and 28.2%, respectively, p < 0.001). Women's socio-demographic background and
      their attitude towards Down syndrome and termination of pregnancy (TOP) had
      contributed independently on CT choice. CONCLUSION: The uptake of the CT in this
      study is low. The main reason for the low uptake is the relatively positive
      attitude towards Down syndrome and a negative attitude towards TOP. Moreover, the
      perception of maternal age as strong predictor of Down syndrome risk and the
      inequality of access to care, due to the financial threshold for younger women,
      are likely to affect participation in screening.

PMID- 23138695
TI  - Absorption Angstrom exponents of aerosols and light absorbing carbon (LAC)
      obtained from in situ data in Covilha, central Portugal.
AB  - A field campaign was conducted from October 2009 to July 2010 at Covilha, a small
      town located in the region of Beira Interior (Portugal) in the interior of the
      Iberian Peninsula. The ambient light-absorption coefficient, sigma(a) (522 nm),
      obtained from a Particle Soot Absorption Photometer (PSAP), presented a daily
      mean value of 12.1 Mm-1 (StD = 7.3 Mm-1). The wavelength dependence of aerosol
      light absorption is investigated through the Angstrom parameter, alpha(a). The
      alpha(a) values for the pair of wavelengths 470-660 nm ranged from 0.86 to 1.47
      during the period of measurements. The PSAP data were used to infer the mass of
      light absorbing carbon (LAC) and the daily mean varied from 0.1 to 6.8 MUg m-3. A
      detailed study of special events with different aerosol characteristics is
      carried out and, to support data interpretation, air masses trajectory analysis
      is performed.

PMID- 23138696
TI  - Association of Tef polymorphism with depression in Parkinson disease.
AB  - BACKGROUND: Circadian rhythm disturbance has been implicated in depression, and
      polymorphisms of circadian genes Cry1, Cry2, and Tef are associated with
      depression. However, the relationship between these genes and depression symptoms
      in Parkinson's disease (PD) has not been established. METHODS: Four hundred eight
      subjects with PD participated in this study. Demographics, UPDRS, Mini-Mental
      Status Examination (MMSE), and Hamilton Rating Scale for Depression (HAMD) were
      obtained in all subjects. Frequency of polymorphisms of Cry1 rs2287161, Cry2
      rs10838524, and Tef rs738499 was determined, and the association between genetic
      polymorphisms of circadian genes and HAMD scores in patients with PD was
      examined. RESULTS: Tef, but not Cry1 or Cry2, is associated with HAMD scores in
      patients with PD in a linear regression model after adjusting for clinical
      variables (P = 0.004). CONCLUSIONS: The polymorphism of Tef rs738499 is
      associated with depression symptoms in PD.

PMID- 23138697
TI  - Common sense paths follow brain injuries.

PMID- 23138698
TI  - In search of an immunobiomarker for Parkinson's disease.

PMID- 23138699
TI  - Implant surface factors and bacterial adhesion: a review of the literature.
AB  - The microbiota that forms on implant surfaces placed in the human body can be
      highly resistant to antimicrobial agents and in some cases cause life-threatening
      infections. Consequently, to limit bacterial attachment to these surfaces and
      thereby minimize the risk of implant infection, the process of biofilm formation
      and bacterial attachment must be well-understood. The oral environment is
      considered to be an excellent model for research into biofilm formation and
      implant infection, accounting for many studies carried out in the field of dental
      medicine. Those studies show that the roughness, free energy, and material
      characteristics of the implant surface largely determine initial bacterial
      adhesion. This article reviews the relevant literature on these aspects of
      biofilm formation.

PMID- 23138700
TI  - Diversity of patients microflora on orthopaedic and dental implants.
AB  - The aim of this study was to compare the diversity of microbial colonization on
      implant material from different individuals. Eubacterial DNA was extracted,
      separated and sequenced from orthopaedic metallic implant material, tissues or
      body fluids, and skin of 4 patients as well as from identical dental cement
      material from 10 individuals after revision and routine removal. Additionally,
      the composition of the bacterial population of the dental cement and the oral
      swab sample from one individual after direct extraction of bacterial DNA was
      compared to extraction after conventional microbiological enrichment. The latter
      investigation proved that the commonly used cultivation technique gave different
      results than direct extraction of DNA, especially as regards the detection of
      anaerobes. Comparing the bacterial colonization of implant materials from
      different patients showed significant individual diversity. The common focus on a
      constricted pathogen spectrum may have to be expanded toward a multispecies
      population. Moreover, the dependence of the bacterial population on the
      individual host has to be integrated in discussing implant colonization and
      infection.

PMID- 23138701
TI  - Prosthetic joint infections due to Staphylococcus aureus and coagulase-negative
      staphylococci.
AB  - PURPOSES: To evaluate the specific characteristics, outcome, and predictors of
      failure of prosthetic joint infections (PJI) due to S. aureus and coagulase
      negative staphylococci (CNS) treated with open debridement and retention of the
      implant. METHODS: PJI due to S. aureus or CNS prospectively registered in a
      database from 1999 to 2009 were retrospectively reviewed. During the study
      period, 106 patients met the inclusion criteria. The mean follow-up period was
      3.8 years and for at least 2 years in all patients. The failure rate was 23.6%
      (25 out of 106). The only variable significantly associated with failure in the
      global cohort was polymicrobial infection (38.7% vs. 17.3%, p = 0.024). Fifty
      seven (53.8%) patients had an infection due to S. aureus and 49 (46.2%) due to
      CNS. Among S. aureus infections, 95% corresponded to primary arthroplasties while
      98% of PJIs due to CNS were after revision arthroplasties (p<0.001). C-reactive
      protein was significantly higher in PJI due to S. aureus (9.5 mg/dl vs. 4.9
      mg/dl, p = 0.007). The rate of methicillin-resistance (8.8% vs. 59.2%, p<0.001)
      and fluoroquinolone-resistance (15.8% vs. 34.7%, p = 0.005) was significantly
      higher in CNS infections. The global failure rate was higher in S. aureus
      infections (28% vs. 18.3. p = 0.26). In S. aureus infections, patients diagnosed
      within the first 15 days after joint arthroplasty (p = 0.031) and with bacteremia
      (p = 0.046) had poor pro-gnosis. In CNS infections only the location of the
      prosthesis (knee 27.6% vs. hip 5%, p = 0.045) was associated with failure.
      CONCLUSIONS: PJIs due to S. aureus were mainly in primary arthroplasties; they
      had a higher inflammatory response; and the strains were more susceptible to
      fluoroquinolones and methicillin than CNS infections. S. aureus infections had a
      higher failure rate than CNS infections, however, the difference was not
      statistically significant. There were few factors associated with failure and
      they were different in S. aureus and CNS infections.

PMID- 23138702
TI  - A novel antibacterial modification treatment of titanium capable to improve
      osseointegration.
AB  - BACKGROUND: Among the different causes of orthopedic and dental implant failure,
      infection remains the most serious and devastating complication associated with
      biomaterial devices. PURPOSE: The aim of this study was to develop an innovative
      osteointegrative and antibacterial biomimetic coating on titanium and to perform
      a chemical-physical and in vitro biological characterization of the coating using
      the SAOS-2 cell line. We also studied the antibacterial properties of the coating
      against both Gram-positive and Gram-negative bacteria strains. METHODS: An
      electrochemical solution containing silicon, calcium, phosphorous, sodium, and
      silver nanoparticles was used to obtain the antibacterial by Anodic Spark
      Deposition (ASD) treatment. Surface morphology was characterized using SEM and
      laser profilometry. A qualitative analysis of the chemical composition of the
      coating was assessed by EDS. The adhesion properties of the coating to the
      titanium bulk were performed with a 3-point bending test. SAOS-2 osteoblastic
      cell line spreading and morphology and viability were investigated. The bacterial
      adhesion and the antibacterial properties were investigated after 3 h and 24 h of
      incubation with Streptococcus mutans, Streptococcus epidermidis, and Escherichia
      coli bacterial strains. RESULTS: The proposed anodization treatment created a
      chemically and morphologically modified, adherent titanium oxide layer,
      characterized by a microporous morphology enriched by calcium, silicon,
      phosphorous, and silver. The preliminary biological characterization showed
      optimal SAOS-2 cell adhesion and proliferation as well as a strong antibacterial
      effect. CONCLUSIONS: Based on the results of this study, we believe that this
      novel biomimetic and antibacterial treatment hold promise for enhancing
      osteointegration while conferring strong antibacterial properties to titanium.

PMID- 23138703
TI  - Electrochemically deposited gentamicin-loaded calcium phosphate coatings for bone
      tissue integration.
AB  - PURPOSE: Despite improvements in operative environment and surgical techniques,
      post-operative infections remain one of the most devastating complications in
      total joint replacement prostheses. Several efforts have been made to modify the
      surface of materials in order to prevent bacterial adhesion and colonization.
      Here, we show a one-pot electrochemical surface modification process for co
      deposition of calcium phosphate and gentamicin, with the aim of triggering
      specific biological responses and imparting antibacterial properties on titanium
      alloy prostheses. METHODS: Gentamicin-loaded calcium phosphate coatings were
      deposited on Ti specimens via cathodic polarization in an electrochemical bath
      containing different amounts of the antibiotic salt (1-10 mg mL-1). Coatings were
      evaluated in terms of chemico-physical properties, via SEM/EDX, XRD, and ICP
      analysis, and antibacterial activity, via agar disc diffusion test on
      Staphylococcus aureus 8325-4 and Staphylococcus aureus SA113. RESULTS: An
      effective incorporation of gentamicin was achieved without any major effect on
      the morphology and structure. Morphology resulted in a typical plate-like
      brushite structure, confirmed by chemical composition and crystallographic
      structure. Gentamicin-loaded coatings showed an antibacterial efficacy on both
      staphlococcal strains, with a dose-dependent activity. CONCLUSIONS:
      Electrochemical technology can be advantageously exploited in order to obtain
      coatings for bone-contact prostheses with tailored antibacterial properties.

PMID- 23138704
TI  - From Koch's postulates to biofilm theory. The lesson of Bill Costerton.
AB  - The clinical diagnoses of implant infections pose insurmountable difficulties for
      cultural methods because of their frequent failure when bacteria are growing in
      biofilms. In 1978 Bill Costerton warned that chronic infections in patients with
      indwelling medical devices were caused by bacteria growing in well-developed
      glycocalyx-enclosed biofilms and that bacteria within biofilms resist antibiotic
      therapies and immune host defenses. Costerton's "biofilm theory" opened two lines
      of scientific endeavor: the study of the biochemistry and genetics of biofilm
      formation and function; and, on the other side, the search for new methods for
      medical diagnosis and treatment of biofilm-centered implant infections.  This
      Editorial and the entire 2012 issue "Focus on Implant Infections" are dedicated
      to the memory of Bill Costerton, recognized worldwide as the Father of Biofilms
      for his innovation and body of work on infections caused by sessile bacteria.
      Bill Costerton was a great scientist, heedful both to the biological aspects of
      biofilms and to the medical challenges of new diagnostic methods and modern
      therapeutic approaches to implant infections. But, most of all, he was a charming
      Maestro for the large number of colleagues and students whose enthusiasm for the
      science he was able to nourish. Bill passed away on May 12th, 2012 and the entire
      science community mourns the death of a friend and a leader.

PMID- 23138705
TI  - Antimicrobial activity of nanocomposite zirconium nitride/silver coatings to
      combat external bone fixation pin infections.
AB  - During external fixation, temporary implants are used to penetrate the skin,
      muscle and bone to support severely fractured bones. This creates a biologically
      critical interface at the site of entry, which potentially allows a risk of
      infection. The aim of this study, therefore, was to investigate potential
      antimicrobial nanocomposites to combat infection. Magnetron sputtering was used
      to produce zirconium nitride/silver nanocomposite coatings, which were prepared
      at two different silver concentrations of 15.5 at.% and 29.8 at.%. These coatings
      were characterized for morphology, chemical composition, and antimicrobial
      activity in comparison to pure zirconium nitride and stainless steel.
      Staphylococcus aureus and Staphylococcus epidermidis were used as in vitro test
      organisms in a range of antimicrobial assays; retention of the bacteria on the
      surfaces and their survival using LiveDeadTM staining; the use of a metabolic
      redox dye to indicate a contact kill and zone of inhibition assays to indicate
      leaching of inhibitory silver ions. Antimicrobial tests demonstrated a
      significant kill when the bacterial cells came in contact with the coatings
      containing silver at both 15.5 at.% and 29.8 at.%. No inhibitory leaching from
      the surfaces occurred. These surfaces demonstrate potential for use as
      antimicrobial fixation pin coatings.

PMID- 23138706
TI  - Epidemiology and new developments in the diagnosis of prosthetic joint infection.
AB  - Although prosthetic joint infection (PJI) is a rare event after arthroplasty, it
      represents a significant complication that is associated with high morbidity,
      need for complex treatment, and substantial healthcare costs. An accurate and
      rapid diagnosis of PJI is crucial for treatment success. Current diagnostic
      methods in PJI are insufficient with 10-30% false-negative cultures.
      Consequently, there is a need for research and development into new methods aimed
      at improving diagnostic accuracy and speed of detection. In this article, we
      review available conventional diagnostic methods for the diagnosis of PJI
      (laboratory markers, histopathology, synovial fluid and periprosthetic tissue
      cultures), new diagnostic methods (sonication of implants, specific and multiplex
      PCR, mass spectrometry) and innovative techniques under development (new
      laboratory markers, microcalorimetry, electrical method, reverse transcription
      [RT]-PCR, fluorescence in situ hybridization [FISH], biofilm microscopy,
      microarray identification, and serological tests). The results of highly
      sensitive diagnostic techniques with unknown specificity should be interpreted
      with caution. The organism identified by a new method may represent a real
      pathogen that was unrecognized by conventional diagnostic methods or
      contamination during specimen sampling, transportation, or processing. For
      accurate interpretation, additional studies are needed, which would evaluate the
      long-term outcome (usually >2 years) with or without antimicrobial treatment. It
      is expected that new rapid, accurate, and fully automatic diagnostic tests will
      be developed soon.

PMID- 23138707
TI  - Antifungal activity against Candida biofilms.
AB  - Candida species have two distinct lifestyles: planktonic, and surface-attached
      communities called biofilms. Mature C. albicans biofilms show a complex three
      dimensional architecture with extensive spatial heterogeneity, and consist of a
      dense network of yeast, hyphae, and pseudohyphae encased within a matrix of
      exopolymeric material. Several key processes are likely to play vital roles at
      the different stages of biofilm development, such as cell-substrate and cell-cell
      adherence, hyphal development, and quorum sensing. Biofilm formation is a
      survival strategy, since biofilm yeasts are more resistant to antifungals and
      environmental stress. Antifungal resistance is a multifactorial process that
      includes multidrug efflux pumps, target proteins of the ergosterol biosynthetic
      pathway. Most studies agree in presenting azoles as agents with poor activity
      against Candida spp. biofilms. However, recent studies have demonstrated that
      echinocandins and amphotericin B exhibit remarkable activity against C. albicans
      and Candida non-albicans biofilms. The association of Candida species with
      biofilm formation increases the therapeutic complexity of foreign body-related
      yeast infections. The traditional approach to the management of these infections
      has been to explant the affected device. There is a strong medical but also
      economical motivation for the development of novel anti-fungal biofilm strategies
      due to the constantly increasing resistance of Candida biofilms to conventional
      antifungals, and the high mortality caused by related infections. A better
      description of the extent and role of yeast in biofilms may be critical for
      developing novel therapeutic strategies in the clinical setting.

PMID- 23138708
TI  - Influence of prophylactic antibiotics on tissue integration versus bacterial
      colonization on poly(methyl methacrylate).
AB  - PURPOSE: Biomaterial-associated infections (BAI) remain a major concern in modern
      health care. BAI is difficult to treat and often results in implant replacement
      or removal. Pathogens can be introduced on implant surfaces during surgery and
      compete with host cells attempting to integrate the implant. Here we studied the
      influence of prophylactically given cephatholin in the competition between highly
      virulent Staphylococcus aureus and human osteoblast-like cells (U-2 OS, ATCC HTB
      94) for a poly(methyl methacrylate) surface in vitro using a peri-operative
      contamination model. METHOD: S. aureus was seeded on the acrylic surface in a
      parallel plate flow chamber prior to adhesion of U-2 OS cells. Next, S. aureus
      and U-2 OS cells were allowed to grow simultaneously under shear (0.14 1/s) in a
      modified culture medium containing cephatholin for 8 h, the time period this drug
      is supposed to be active in situ. Subsequently, the flow was continued with
      modified culture medium for another 64 h. RESULTS: In the absence of cephatholin,
      highly virulent S. aureus caused U-2 OS cell death within 18 h. In contrast, the
      presence of cephatholin for 8 h resulted in survival of U-2 OS cell up to 72 h
      during simultaneous growth of U-2 OS cells and bacteria. Not all adhering
      bacteria were killed however, but they showed a delayed growth. CONCLUSIONS:
      These findings are in line with the recalcitrance of biofilms against antibiotic
      treatment observed clinically, and represent another support for the use of in
      vitro co-culture models in mimicking the clinical situation.

PMID- 23138709
TI  - The use of antimicrobial-impregnated PMMA to manage periprosthetic infections:
      controversial issues and the latest developments.
AB  - Despite improvements in intraoperative antimicrobial procedures, in surgical
      techniques and in implant design for joint replacement, periprosthetic infection
      after arthroplasty is still one of the most challenging problems encountered by
      orthopedic surgeons. Systemic antibiotics are not sufficiently effective to
      eradicate such deep infections because of the impaired blood circulation and low
      antibiotic concentration at the implantation site. As a local drug delivery
      system, antibiotic-impregnated PMMA (polymethylmethacrylate) bone cements have
      been widely used for prophylaxis or treatment of deep infections after total
      joint replacement. However, the effectiveness of antibiotic-loaded PMMA in
      preventing infections after arthroplasty is still controversial. Furthermore, the
      outcomes of established deep infections treated with this technique are not
      consistent. The local use of antibiotics has led to the emergence of antibiotic
      resistant bacterial strains and has adverse effects on the function of osteogenic
      cells. Recently, many efforts have been made to identify new antibacterial agents
      that can be loaded into PMMA. These antimicrobial agents should exhibit good
      antibacterial activity against antibiotic-resistant strains and should
      simultaneously enhance osteointegration between the PMMA and the bone tissue.
      PMMA loaded with chitosan or chitosan derivatives has been demonstrated to induce
      improved osteogenic activity and to exhibit antibacterial activity in a
      preclinical study.

PMID- 23138710
TI  - Biofilm formation on composite resins for dental restorations: an in situ study
      on the effect of chlorhexidine mouthrinses.
AB  - PURPOSE: Biofilm formation on the surface of dental restorative materials by oral
      bacteria is considered an important step in the development of secondary caries.
      The aim of this study was to evaluate the in situ effect of a chlorhexidine (CHX)
      containing mouthrinse on the biofilm formation occurring on the surface of human
      enamel and of two resin-based commercially available materials: a silorane-based
      material (Filtek Silorane(r)) and a methacrylate-based material (Filtek Supreme
      XT(r)). METHODS: 53 disks were obtained for each of the two composites and 37
      disks for enamel. The surface was characterized by determining the surface
      roughness and the surface free energy of 5 samples for each of the three
      materials tested, then the remaining samples were mounted on splints worn by 16
      volunteers. The participants were randomly divided into two groups: an
      experimental group that used 0.12% CHX-based mouthrinse and a control group that
      used a placebo mouthrinse. Biofilm formation on the different surfaces after a 24
      h period was assessed using MTT assay. RESULTS: The two composites in the group
      treated with the placebo mouthrinse showed a similar biofilm formation, which was
      significantly higher than that occurring on enamel surfaces. The CHX-based
      mouthrinse significantly reduced biofilm formation on the surfaces of the two
      resin-based materials when compared with the placebo mouthrinse. The reduction
      was particularly relevant on the Filtek Silorane surfaces. CONCLUSIONS: The new
      silorane-based material seems to interact with CHX in a promising way from the
      point of view of biofilm formation control.

PMID- 23138711
TI  - Constructing a large variety of Dirac-cone materials in the Bi(1-x)Sb(x) thin
      film system.
AB  - We theoretically predict that a large variety of Dirac-cone materials can be
      constructed in Bi(1-x)Sb(x) thin films and we here show how to construct single-,
      bi- and tri-Dirac-cone materials with various amounts of wave vector anisotropy.
      These different types of Dirac cones can be of special interest to electronic
      device design, quantum electrodynamics and other fields.

PMID- 23138712
TI  - Microbial cultivation and the role of microbial resource centers in the omics
      era.
AB  - Despite tremendous advances in microbial ecology over the past two decades,
      traditional cultivation methods have failed to grow ecologically more relevant
      microorganisms in the laboratory, leading to a predominance of weed-like species
      in the world's culture collections. In this review, we highlight the gap between
      culture-based and culture-independent methods of microbial diversity analysis,
      especially in investigations of slow growers, oligotrophs, and fastidious and
      recalcitrant microorganisms. Furthermore, we emphasize the importance of
      microbial cultivation and the acquisition of the cultivation-based phenotypic
      data for the testing of hypotheses arising from genomics and proteomics
      approaches. Technical difficulties in cultivating novel microorganisms and how
      modern approaches have helped to overcome these limitations are highlighted.
      After cultivation, adequate preservation without changes in genotypic and
      phenotypic features of these microorganisms is necessary for future research and
      training. Hence, the contribution of microbial resource centers in the handling,
      preservation, and distribution of this novel diversity is discussed. Finally, we
      explore the concept of microbial patenting and requisite guidelines of the
      "Budapest Treaty" for establishment of an International Depositary Authority.

PMID- 23138713
TI  - Extrachromosomal genetic elements in Micrococcus.
AB  - Micrococci are Gram-positive G + C-rich, nonmotile, nonspore-forming
      actinomycetous bacteria. Micrococcus comprises ten members, with Micrococcus
      luteus being the type species. Representatives of the genus play important roles
      in the biodegradation of xenobiotics, bioremediation processes, production of
      biotechnologically important enzymes or bioactive compounds, as test strains in
      biological assays for lysozyme and antibiotics, and as infective agents in
      immunocompromised humans. The first description of plasmids dates back
      approximately 28 years, when several extrachromosomal elements ranging in size
      from 1.5 to 30.2 kb were found in Micrococcus luteus. Up to the present, a number
      of circular plasmids conferring antibiotic resistance, the ability to degrade
      aromatic compounds, and osmotolerance are known, as well as cryptic elements with
      unidentified functions. Here, we review the Micrococcus extrachromosomal traits
      reported thus far including phages and the only quite recently described large
      linear extrachromosomal genetic elements, termed linear plasmids, which range in
      size from 75 kb (pJD12) to 110 kb (pLMA1) and which confer putative advantageous
      capabilities, such as antibiotic or heavy metal resistances (inferred from
      sequence analyses and curing experiments). The role of the extrachromosomal
      elements for the frequently proven ecological and biotechnological versatility of
      the genus will be addressed as well as their potential for the development and
      use as genetic tools.

PMID- 23138714
TI  - Two novel Physcomitrella patens fatty acid elongases (ELOs): identification and
      functional characterization.
AB  - The lower plant Physcomitrella patens synthesizes several long-chain
      polyunsaturated fatty acids (LC-PUFAs) by a series of desaturation and elongation
      reactions. In the present study, the full-length cDNAs for two novel fatty acid
      elongases designated PpELO1 and PpELO2 were isolated from P. patens using a PCR
      based cloning strategy. These cDNAs encoding proteins of 335 and 280 amino acids
      with predicted molecular masses of 38.7 and 32.9 kDa, respectively, are predicted
      to contain seven transmembrane domains with a possible localization in the
      subcellular endoplasmic reticulum. Sequence comparisons and phylogenetic analysis
      revealed that they are closely related to other LC-PUFA elongases of the lower
      eukaryotes such as the Delta(5)- and Delta(6)-elongases of Marchantia polymorpha
      as well as the Delta(6)-elongase of P. patens. Heterologous expression of the
      PpELO1 in Saccharomyces cerevisiae led to the elongation of Delta(9)-, Delta(6)
      C18, and Delta(5)-C20 LC-PUFAs, whereas only Delta(9)- and Delta(6)-C18 LC-PUFA
      substrates were used by PpELO2. Chimeric proteins were constructed to identify
      the amino acid regions most likely to be involved in the determination of the
      fatty acid substrate specificity. The expression of eight chimeric proteins in
      yeast revealed that substitution of the C-terminal 50 amino acids from PpELO1
      into PpELO2 resulted in a high specificity for C20 fatty acid substrates. As a
      result, we suggest that the C-terminal region of PpELO1 is sufficient for C20
      substrate elongation. Overall, these results provide important insights into the
      structural basis for substrate specificity of PUFA-generating ELO enzymes.

PMID- 23138715
TI  - Synthesis of blue emitting InP/ZnS quantum dots through control of competition
      between etching and growth.
AB  - Blue (<480 nm) emitting Cd-free quantum dots (QDs) are in great demand for
      various applications. However, their synthesis has been challenging. Here we
      present blue emitting InP/ZnS core/shell QDs with a band edge emission of 475 nm
      and a full width at half maximum of 39 nm (215 meV) from their quantum confined
      states. The drastic temperature drop immediately after mixing of the precursors
      and holding them at a temperature below 150  degrees C was the critical factor
      for the synthesis of blue emitting QDs, because the blue QDs are formed by the
      etching of ultra-small InP cores by residual acetic acid below 150  degrees C.
      Etching was dominant at temperatures below 150  degrees C, whereas growth was
      dominant at temperatures above 150  degrees C. ZnS shells were formed
      successfully at 150  degrees C, yielding blue emitting InP/ZnS QDs. The colour of
      the InP/ZnS QDs depicted on the CIE 1931 chromaticity diagram is located close to
      the edge, indicating a pure blue colour compared to other InP-based QDs.

PMID- 23138717
TI  - Lady Prelox(r) improves sexual function in post-menopausal women.
AB  - AIM:he aim of this pilot, single-blinded study was to evaluate the efficacy of a
      proprietary, dietary supplement Lady Prelox(r) for supporting and improving
      sexual function in generally healthy, post-menopausal women. METHODS: The Lady
      Prelox(r) and placebo control groups were comparable at inclusion with regard to
      the total Female Sexual Function Index (FSFI) score, as well as for the six
      individual FSFI domains, with 40 women (50.1+/-3.1 years) and 43 women (51.2+/
      2.3 years), respectively. RESULTS:At baseline the women in the verum group
      presented with a mean total FSFI score of 44.6+/-24.1 which increased
      significantly already after four weeks treatment with Lady Prelox(r) to 70.9+/
      18.5 and further increased to 71.7+/-23.9 after completion of the eight-week
      trial period. In the control group the mean total FSFI was 44.1+/-22.8 at
      inclusion and non-significantly increased to 45+/-21.4 after four weeks and
      47.4+/-21.8 after eight weeks, respectively. The treatment with Lady Prelox(r)
      was comparatively significantly more effective than placebo after both four and
      eight weeks of treatment (P<0.05). The individual six FSFI domains related to
      desire, arousal, lubrication, orgasm, satisfaction and pain did all respond
      favourably to treatment with Lady Prelox(r); however, with only marginable higher
      scores in the placebo group. Four women in each group dropped out because of
      inabilities to attend scheduled check-ups. No adverse effects were reported.
      CONCLUSION: This study opens an interesting perspective for women experiencing
      moderate sexual function impairment and suggests a promising new treatment
      option. Further studies with larger numbers of women, including also
      premenopausal and perimenopausal women are warranted.

PMID- 23138719
TI  - Guanine-based purines modulate the effect of L-NAME on learning and memory in
      rats.
AB  - Guanosine has been reported to exert neuroprotective effects. We recently
      reported that, following intraperitoneal (i.p.) injection to rats, it resulted to
      be widely distributed. Its metabolic product guanine also rapidly increased in
      all the tissues, including brain, after i.p. injection of guanosine and
      consistently we found a significant enzymatic activity of a soluble purine
      nucleoside phosphorylase in the plasma of the treated animals. In this study the
      effect of per os administration of guanosine or guanine to rats submitted to
      passive avoidance task has been evaluated. Guanosine (4 and 8 mg/kg) administered
      pretraining impaired retention in the passive avoidance task and was unable to
      prevent the amnesic effect caused by 100 mg/kg N-omega-nitro-l-arginine methyl
      ester (L-NAME), an inhibitor of the nitric oxide synthase (NOS) known to reduce
      the capability of treated animals to acquire or retain informations in several
      learning tasks. On the contrary, guanine (4 and 8 mg/kg), which per se did not
      modify the latency to step-trough in the passive avoidance task, when
      administered pretraining 15 min before L-NAME prevented, in a dose dependent
      manner, the amnesic effect of the NOS inihibitor. Moreover the nucleobase was
      able to rescue the memory trace also when administered after training. Neither
      guanosine nor guanine had effects on locomotor activity. These results indicate
      that guanine can exert important biological activities which may be different
      from those mediated by its precursor guanosine, thus this evenience should be
      taken into account when the biological effects of guanosine are evaluated.

PMID- 23138725
TI  - Keratoconjunctivitis by confocal microscopy after topical cyclosporine.
AB  - AIM: To describe the observations obtained by confocal microscopy concerning
      corneal stromal structure in the process of adenoviral epidemic
      keratoconjunctivitis, from the onset of the disease up to 20 weeks of follow-up,
      after topical cyclosporine. METHODS: A 16-years-old boy has developed
      subepithelial infiltrates and an epidemic keratoconjunctivitis from adenovirus in
      both eyes. Clinical case was analyzed by confocal microscopy (40x mode, Nidek
      ConfoScan 4) before and after administration of topical cyclosporine. RESULTS:
      Two weeks after the onset of the symptoms, corneal stroma showed the presence of
      cells with highly reflective area. These cells, comparable to keratocytes, had a
      typical fusiform shape and assumed a particular rosette disposition, never
      highlighted in the literature. Hyperreflective areas disappeared in both eyes
      after administration of topical cyclosporine 1% for 30 days. This outcome was
      also confirmed after five months. CONCLUSION: The confocal microscopy performed
      on the surface of the stroma before and after treatment with cyclosporine
      suggests the presence of a localized immune activation in subepithelial layer.

PMID- 23138726
TI  - Retrospective study of glaucoma and closed-eyelid test: long-term outcomes in an
      Italian native population.
AB  - AIM: To establish a threshold value of intraocular pressure (IOP) increase after
      the closed-eyelid test (CET) that correlates with the highest probability of
      developing overt primary open-angle glaucoma (OAG) in an Italian native
      population from 1980 to 2010. METHODS: Retrospective analysis of data obtained
      from 161 patients with ocular hypertension who performed the CET in 1980, and
      were subsequently followed to see whether they developed OAG. CET was performed
      always in the morning Eyelids were closed by bandaging for 1 h in a quiet
      environment, with the patient seated and not sleeping. IOP was measured again 8
      to 10s after opening the eyelids. RESULTS: Accurate statistical analysis of the
      obtained values indicated that 77% of the subjects showing an IOP increase after
      1 hour of eyelid closure in a sitting position developed OAG in the following 30
      years and that IOP increase values above 4 mmHg led to a subsequent diagnosis of
      glaucoma in more than 80% of the patients. CONCLUSION: Eyelid closure for 60
      minutes results in a net elevation of IOP the extent of which depends on the
      balance between the increase of aqueous humour secretion and its outflow.
      Therefore, the CET may discriminate individuals with a normal outflow from
      individuals with a less functional outflow, which are evidently those at a higher
      risk of developing glaucoma.

PMID- 23138727
TI  - Optical Coherence Tomography evaluation in X-linked retinoschisis.
AB  - X-linked Retinoschisis is a bilateral retinal disease with a recessive X-linked
      inheritance, characterized by a macular involvement. Maculopathy consists of
      bilateral star-shaped microcystic changes. Peripheral retina is sometimes
      involved with schisis. In two years, were examined 10 eyes of 5 male patients
      (age range 20-25 years old) with X-linked Juvenile Retinoschisis and progressive
      reduction of visual acuity. Macular alterations were classified as: Typical
      foveal schisis; Altered foveal reflection; Lines of pigmentary demarcation;
      Retinal pigmentary epithelium atrophy; Hole in retinal internal layer. OCT images
      showed a separation of neurosensorial retina that coincided with classical
      histopathological findings. Examination results were correlated with clinical
      examination and compared with ERG findings. OCT images underline an increase of
      retinal thickness with a separation in the nerve fiber layer in the foveal space.

PMID- 23138728
TI  - The relationship between grey-matter and ASD and ADHD traits in typical adults.
AB  - We tested whether in 85 healthy adults (18-29 years) there is a relationship
      between grey-matter (GM) volume and autism and ADHD symptom severity. The
      structural MRI findings and autism and ADHD self-reports revealed that autism and
      ADHD symptom severity was correlated with GM volume in the left inferior frontal
      gyrus. Autism symptom-severity was correlated with the left posterior cingulate,
      ADHD with the right parietal lobe, right temporal frontal cortex, bilateral
      thalamus, and left hippocampus/amygdala complex. Symptom severity of both
      disorders form a continuum extending into the general population, but it seems to
      be an oversimplification to typify psychiatric disorders such as autism and ADHD
      solely as extremes of brain structure abnormalities.

PMID- 23138729
TI  - Salient social cues are prioritized in autism spectrum disorders despite overall
      decrease in social attention.
AB  - Diminished social attention is often considered to be a central deficit in autism
      spectrum disorders (ASDs). We further investigate this hypothesis by measuring
      the distracting power of social and non-social stimuli in the context of a Stroop
      task among children with ASD and typically developing controls (TDCs). Our
      results show that Stroop interference increases with social versus non-social
      distracters in TDCs, whereas the opposite pattern occurs in ASD. Within social
      stimuli, however, the superiority of direct gaze previously reported in the
      literature did not differ between the groups. Our data thus suggest that ASD
      children assign less weight to social than non-social stimuli, but that within
      social signals, salient stimuli remain prioritized.

PMID- 23138730
TI  - Acceptability of fingerprint scanning for personal identification among patients
      seeking HIV/STI-related services, Los Angeles, 2011.

PMID- 23138731
TI  - Drug-resistant virus has reduced ability to induce immune activation.

PMID- 23138732
TI  - Self-Report of Alcohol Use Increases When Specimens for Alcohol Biomarkers Are
      Collected in Persons With HIV in Uganda.

PMID- 23138734
TI  - Decreased phagocytic function in neutrophils and monocytes from peripheral blood
      in periodontal disease.
AB  - Phagocytosis by neutrophils and monocytes constitutes the main defense mechanism
      against bacterial challenges in periodontitis. Phagocytosis by neutrophils has
      already been evaluated, whereas phagocytic function of monocytes has hardly been
      addressed so far. OBJECTIVES: The aim of this study was to assess phagocytosis by
      neutrophils and monocytes in periodontitis. MATERIAL AND METHODS: The sample
      included 30 subjects with severe periodontitis and 27 control subjects without
      periodontal disease. The phagocytic index (PhI) was calculated as the mean number
      of adhered/ingested Saccharomyces cerevisiae per phagocytozing monocyte or
      neutrophil multiplied by the percentage of phagocytes involved in phagocytosis.
      RESULTS: A significant reduction in phagocyte functions was observed in
      individuals with periodontitis. The median of PhI of neutrophils using
      nonsensitized S. cerevisiae was 3 for the control group, and 1.5 for the
      periodontitis group (p=0.01, Mann-Whitney test). The median of PhI of monocytes
      with non-sensitized S. cerevisiae was 26.13 for the control group, and 13.23 for
      the periodontitis group (p=0.03, Mann Whitney test). The median of PhI of
      monocytes assessed with sensitized S. cerevisiae was 97.92 for the control group
      and 60.1 for the periodontitis group (p=0.005, t-test). CONCLUSION: The data
      demonstrated a reduction in the function of phagocytes, suggesting a decrease in
      immune defenses in periodontitis.

PMID- 23138733
TI  - Saliva and dental erosion.
AB  - Dental erosion is a multifactorial condition. The consideration of chemical,
      biological and behavioral factors is fundamental for its prevention and therapy.
      Among the biological factors, saliva is one of the most important parameters in
      the protection against erosive wear. OBJECTIVE: This review discusses the role of
      salivary factors on the development of dental erosion. MATERIAL AND METHODS: A
      search was undertaken on MeDLINe website for papers from 1969 to 2010. The
      keywords used in the research were "saliva", "acquired pellicle", "salivary
      flow", "salivary buffering capacity" and "dental erosion". Inclusion of studies,
      data extraction and quality assessment were undertaken independently and in
      duplicate by two members of the review team. Disagreements were solved by
      discussion and consensus or by a third party. RESULTS: Several characteristics
      and properties of saliva play an important role in dental erosion. Salivary
      clearance gradually eliminates the acids through swallowing and saliva presents
      buffering capacity causing neutralization and buffering of dietary acids.
      Salivary flow allows dilution of the acids. In addition, saliva is supersaturated
      with respect to tooth mineral, providing calcium, phosphate and fluoride
      necessary for remineralization after an erosive challenge. Furthermore, many
      proteins present in saliva and acquired pellicle play an important role in dental
      erosion. CONCLUSIONS: Saliva is the most important biological factor affecting
      the progression of dental erosion. Knowledge of its components and properties
      involved in this protective role can drive the development of preventive measures
      targeting to enhance its known beneficial effects.

PMID- 23138735
TI  - Impact of filler size and distribution on roughness and wear of composite resin
      after simulated toothbrushing.
AB  - OBJECTIVES: Nanofilled composite resins are claimed to provide superior
      mechanical properties compared with microhybrid resins. Thus, the aim of this
      study was to compare nanofilled with microhybrid composite resins. The null
      hypothesis was that the size and the distribution of fillers do not influence the
      mechanical properties of surface roughness and wear after simulated toothbrushing
      test. MATERIAL AND METHODS: Ten rectangular specimens (15 mm x 5 mm x 4 mm) of
      Filtek Z250 (FZ2), Admira (A), TPH3 (T),Esthet-X (EX), estelite sigma (ES),
      concept advanced (C), Grandio (G) and Filtek Z350 (F) were prepared according to
      manufacturer's instructions. Half of each top surface was protected with nail
      polish as control surface (not brushed) while the other half was assessed with
      five random readings using a roughness tester (Ra). Following, the specimens were
      abraded by simulated toothbrushing with soft toothbrushes and slurry comprised of
      2:1 water and dentifrice (w/w). 100,000 strokes were performed and the brushed
      surfaces were reanalyzed. Nail polish layers were removed from the specimens so
      that the roughness (Ra) and the wear could be assessed with three random readings
      (um). Data were analyzed by ANOVA and Tukey's multiple-comparison test
      (alpha=0.05). RESULTS: Overall outcomes indicated that composite resins showed a
      significant increase in roughness after simulated toothbrushing, except for
      Grandio, which presented a smoother surface. Generally, wear of nanofilled resins
      was significantly lower compared with microhybrid resins. CONCLUSIONS: As
      restorative materials suffer alterations under mechanical challenges, such as
      toothbrushing, the use of nanofilled materials seem to be more resistant than
      microhybrid composite resins, being less prone to be rougher and worn.

PMID- 23138736
TI  - A new portable vibrator for plaster pouring: effect on the marginal fit at
      cylinder-abutment.
AB  - OBJECTIVE: The aim of this study was to test a new portable vibrator for plaster
      pouring (developed for this purpose), comparing the effect of its use on the
      accuracy of working cast of implant-supported restorations to the conventional
      vibrator. MATERIAL AND METHODS: From a master cast with 2 implants, 30 transfer
      moldings were made randomly and divided into three groups: group I (GI): pouring
      performed in an outsourced dental laboratory with conventional plaster vibrator
      (10 casts), group II (GII): pouring performed in the laboratory of the Federal
      University of Santa Catarina (UFSC) with conventional plaster vibrator (10 casts)
      and group III (GIII): pouring performed with the portable vibrator fabricated for
      this study (10 casts). The position of the analogue and marginal adaptation of
      the infrastructure were verified by testing the single screw on the master model
      and on the working model. The measurement of misfit was blindly performed with a
      precision microscope and analyzing unit, Quadra-Check 200. The data were
      statistically analyzed by analysis of variance (ANOVA) and the Holm-Sidak test
      (alpha=0.05). RESULTS: Means+/-standard deviations were as follows: GI: 19.19+/
      4.73 um; GII: 21.72+/-5.41 um; GIII: 13.5+/-2.39 um (P<0.05), with GIII
      significantly lower as compared to the other groups. CONCLUSION: Within the
      limitations of this study, it was concluded that a greater accuracy of working
      cast was achieved when a portable vibrator was used for casting molds.

PMID- 23138737
TI  - In vivo accuracy of conventional and digital radiographic methods in confirming
      root canal working length determination by Root ZX.
AB  - OBJECTIVES: To compare, in vivo, the accuracy of conventional and digital
      radiographic methods in determining root canal working length. MATERIAL AND
      METHODS: Twenty-five maxillary incisor or canine teeth from 22 patients were used
      in this study. Considering the preoperative radiographs as the baseline, a 25 K
      file was inserted into the root canal to the point where the Root ZX electronic
      apex locator indicated the APEX measurement in the screen. From this measurement,
      1 mm was subtracted for positioning the file. The radiographic measurements were
      made using a digital sensor (Digora 1.51) or conventional type-E films, size 2,
      following the paralleling technique, to determine the distance of the file tip
      and the radiographic apex. RESULTS: The Student "t" test indicated mean distances
      of 1.11 mm to conventional and 1.20 mm for the digital method and indicated a
      significant statistical difference (p<0.05). CONCLUSIONS: The conventional
      radiographic method was found to be superior to the digital one in determining
      the working length of the root canal.

PMID- 23138738
TI  - Histomorphometric analysis of the temporal bone after change of direction of
      force vector of mandible: an experimental study in rabbits.
AB  - OBJECTIVES: The present study aimed at performing a histological evaluation of
      the response of temporal bone tissue to a change of direction of the force vector
      of the mandible in relation to the base of the skull. MATERIAL AND METHODS: Adult
      rabbits were assigned into four groups with two control and four experimental
      animals in each group. experimental animals underwent surgery, which resulted in
      a change of direction of the force vector on the right temporomandibular joint.
      Samples were collected after 15, 30, 60 and 90 days for histological analysis.
      RESULTS: In the two-way analysis of variance, the effect of group and time was
      statistically significant (p<0.001). Additionally, a statistically significant
      interaction between group and time was observed (p<0.001). Control animals showed
      normal growth and development of the temporal region. In the experimental group,
      the change in direction of the force vector of the mandible induced significant
      changes in the temporal bone, with a bone modeling process, which suggests growth
      of this cranial structure. CONCLUSIONS: The methodology used in this experiment
      allows us to conclude that the change in direction of the force vector of the
      mandible in relation to the skull base induces remodeling and modeling processes
      in the temporal bone. The resumption of normal oral functions after bone healing
      of the mandibular fracture appears to increase cell activation in the remodeling
      and modeling of the temporal bone structure. The observation of areas of temporal
      bone modeling shows the relevance of further investigation on the correlation
      between the joint structures and craniofacial growth and development.

PMID- 23138739
TI  - Dentoalveolar comparative study between removable and fixed cribs, associated to
      chincup, in anterior open bite treatment.
AB  - OBJECTIVE: The aim of this prospective study was to compare the dentoalveolar
      effects produced by two types of palatal crib, removable (Rpc+C) and fixed
      (Fpc+C), combined with chincup in growing patients with anterior open bite.
      MATERIAL AND METHODS: each group comprised 30 patients, in the mixed dentition
      phase, with similar cephalometric characteristics and skeletal ages. Group 1
      (Rpc+C) presented initial mean age of 8.3 years and mean anterior open bite of
      4.0 mm. Group 2 (Fpc+C) presented initial mean age of 8.54 years and mean
      anterior open bite of 4.3 mm. The evaluation period comprised 12 months between
      initial (T1) and second lateral radiograph (T2). The T2-T1 changes were compared
      cephalometrically in the 2 groups using the non-paired t-test. RESULTS: Vertical
      changes in the posterior dentoalveolar region were similar between the groups
      (about 1 mm) and no significant differences were found in molar mesialization.
      The Fpc+C group had in average 1.6 mm more improvement of the overbite as a
      result of greater maxillary incisor extrusion (1.3 mm). Patients in this group
      also presented less lingual tipping of maxillary incisors and more mandibular
      incisors uprighting. CONCLUSIONS: The Fpc+C combination was more efficient in the
      correction of the negative overbite mainly due to greater extrusion of the
      maxillary incisors. However, the Rpc+C appliance promoted better upper and lower
      incisor inclination, resulting in a more adequate overjet.

PMID- 23138740
TI  - Effect of pre-flaring and file size on the accuracy of two electronic apex
      locators.
AB  - OBJECTIVE: This ex vivo study evaluated the effect of pre-flaring and file size
      on the accuracy of the Root ZX and Novapex electronic apex locators (EALs).
      MATERIAL AND METHODS: The actual working length (WL) was set 1 mm short of the
      apical foramen in the palatal root canals of 24 extracted maxillary molars. The
      teeth were embedded in an alginate mold, and two examiners performed the
      electronic measurements using #10, #15, and #20 K-files. The files were inserted
      into the root canals until the "0.0" or "APEX" signals were observed on the LED
      or display screens for the Novapex and Root ZX, respectively, retracting to the
      1.0 mark. The measurements were repeated after the preflaring using the S1 and SX
      Pro-Taper instruments. Two measurements were performed for each condition and the
      means were used. Intra-class correlation coefficients (ICCs) were calculated to
      verify the intra- and inter-examiner agreement. The mean differences between the
      WL and electronic length values were analyzed by the three-way ANOVA test
      (p<0.05). RESULTS: ICCs were high (>0.8) and the results demonstrated a similar
      accuracy for both EALs (p>0.05). Statistically significant accurate measurements
      were verified in the pre-flared canals, except for the Novapex using a #20 K
      file. CONCLUSIONS: The tested EALs showed acceptable accuracy, whereas the pre
      flaring procedure revealed a more significant effect than the used file size.

PMID- 23138741
TI  - Quantitative analysis of S. mutans and S. sobrinus cultivated independently and
      adhered to polished orthodontic composite resins.
AB  - In orthodontics, fixed appliances placed in the oral cavity are colonized by
      microorganisms. OBJECTIVE: The purpose of this study was to quantitatively
      determine the independent bacterial colonization of S. mutans and S. sobrinus in
      orthodontic composite resins. MATERIAL AND METHODS: Seven orthodontic composite
      adhesives for bonding brackets were selected and classified into 14 groups; (GIm,
      GIs) Enlight, (GIIm, GIIs) Grengloo, (GIIIm, GIIIs) Kurasper F, (GIVm, GIVs)
      BeautyOrtho Bond, (GVm, GVs) Transbond CC, (GVIm, GVIs) Turbo Bond II, (GVIIm,
      GVIIs) Blugloo. 60 blocks of 4x4x1 mm of each orthodontic composite resin were
      made (total 420 blocks), and gently polished with sand-paper and ultrasonically
      cleaned. S. mutans and S. sobrinus were independently cultivated. For the
      quantitative analysis, a radioactive marker was used to codify the bacteria (3H)
      adhered to the surface of the materials. The blocks were submerged in a solution
      with microorganisms previously radiolabeled and separated (210 blocks for S.
      mutans and 210 blocks for S. sobrinus) for 2 hours at 37 oC. Next, the blocks
      were placed in a combustion system, to capture the residues and measure the
      radiation. The statistical analysis was calculated with the ANOVA test (Sheffe
      post-hoc). RESULTS: Significant differences of bacterial adhesion were found
      amongst the groups. In the GIm and GIs the significant lowest scores for both
      microorganisms were shown; in contrast, the values of GVII for both bacteria were
      significantly the highest. CONCLUSIONS: This study showed that the orthodontic
      composite resin evaluated in the GIm and GIs, obtained the lowest adherence of S.
      mutans and S. sobrinus, which may reduce the enamel demineralization and the risk
      of white spot lesion formation.

PMID- 23138742
TI  - The influence of surface treatment on the implant roughness pattern.
AB  - An important parameter for the clinical success of dental implants is the
      formation of direct contact between the implant and surrounding bone, whose
      quality is directly influenced by the implant surface roughness. A screw-shaped
      design and a surface with an average roughness of Sa of 1-2 um showed a better
      result. The combination of blasting and etching has been a commonly used surface
      treatment technique. The versatility of this type of treatment allows for a wide
      variation in the procedures in order to obtain the desired roughness. OBJECTIVES:
      To compare the roughness values and morphological characteristics of 04 brands of
      implants, using the same type of surface treatment. In addition, to compare the
      results among brands, in order to assess whether the type of treatment determines
      the values and the characteristics of implant surface roughness. MATERIAL AND
      METHODS: Three implants were purchased directly from each selected company in the
      market, i.e., 03 Brazilian companies (Biomet 3i of Brazil, Neodent and
      Titaniumfix) and 01 Korean company (Oneplant). The quantitative or numerical
      characterization of the roughness was performed using an interferometer. The
      qualitative analysis of the surface topography obtained with the treatment was
      analyzed using scanning electron microscopy images. RESULTS: The evaluated
      implants showed a significant variation in roughness values: Sa for Oneplant was
      1.01 um; Titaniumfix reached 0.90 um; implants from Neodent 0.67 um, and Biomet
      3i of Brazil 0.53 um. Moreover, the SEM images showed very different patterns for
      the surfaces examined. CONCCLUSIONS: The surface treatment alone is not able to
      determine the roughness values and characteristics.

PMID- 23138744
TI  - A study of the distobuccal root canal orifice of the maxillary second molars in
      Chinese individuals evaluated by cone-beam computed tomography.
AB  - As is commonly understood, the root canal morphology of the maxillary molars is
      usually complex and variable. It is sometimes difficult to detect the distobuccal
      root canal orifice of a maxillary second molar with root canal treatment. No
      literature related to the distobuccal root canals of the maxillary second molars
      has been published. OBJECTIVE: To investigate the position of the distobuccal
      root canal orifice of the maxillary second molars in a Chinese population using
      cone-beam computed tomography (CBCT). MATERIAL AND METHODS: In total, 816
      maxillary second molars from 408 patients were selected from a Chinese population
      and scanned using CBCT. The following information was recorded: (1) the number of
      root canals per tooth, (2) the distance between the mesiobuccal and distobuccal
      root canal orifice (DM), (3) the distance between the palatal and distobuccal
      root canal orifice (DP), (4) the angle formed by the mesiobuccal, distobuccal and
      palatal root canal orifices (?PDM). DM, DP and ?PDM of the teeth with three or
      four root canals were analyzed and evaluated. RESULTS: In total, 763 (93.51%) of
      816 maxillary second molars had three or four root canals. The distance between
      the mesiobuccal and distobuccal orifice was 0.7 to 4.8 mm. 621 (81.39%) of 763
      teeth were distributed within 1.5-3.0 mm. The distance between the palatal and
      distobuccal orifice ranged from 0.8 mm to 6.7 mm; 585 (76.67%) and were
      distributed within 3.0-5.0 mm. The angle (?PDM) ranged from 69.4o to 174.7o in
      708 samples (92.80%), the angle ranged from 90o to 140o. CONCLUSIONS: The
      position of the distobuccal root canal orifice of the maxillary second molars
      with 3 or 4 root canals in a Chinese population was complex and variable.
      Clinicians should have a thorough knowledge of the anatomy of the maxillary
      second molars.

PMID- 23138743
TI  - Effects of curing protocol and storage time on the micro-hardness of resin
      cements used to lute fiber-reinforced resin posts.
AB  - OBJECTIVES: To determine the micro-hardness profile of two dual cure resin
      cements (RelyX-U100, 3M-eSPe and Panavia F 2.0, Kuraray) used for cementing
      fiberre inforced resin posts (Fibrekor-Jeneric Pentron) under three different
      curing protocols and two water storage times. MATERIAL AND METHODS: Sixty 16 mm
      long bovine incisor roots were endodontically treated and prepared for
      cementation of the Fibrekor posts. The cements were mixed as instructed,
      dispensed in the canal, the posts were seated and the curing performed as
      follows: (a) no light activation; (b) light-activation immediately after seating
      the post, and; (c) light-activation delayed 5 minutes after seating the post. The
      teeth were stored in water and retrieved for analysis after 7 days and 3 months.
      The roots were longitudinally sectioned and the microhardness was determined at
      the cervical, middle and apical regions along the cement line. The data was
      analyzed by the three-way ANOVA test (curing mode, storage time and thirds) for
      each cement. The Tukey test was used for the post-hoc analysis. RESULTS: Light
      activation resulted in a significant increase in the microhardness. This was more
      evident for the cervical region and for the Panavia cement. Storage in water for
      3 months caused a reduction of the micro-hardness for both cements. The U100
      cement showed less variation in the micro-hardness regardless of the curing
      protocol and storage time. CONCLUSIONS: The micro-hardness of the cements was
      affected by the curing and storage variables and were material-dependent.

PMID- 23138745
TI  - Analysis by confocal laser scanning microscopy of the MDPB bactericidal effect on
      S. mutans biofilm CLSM analysis of MDPB bactericidal effect on biofilm.
AB  - Since bacteria remain in the dentin following caries removal, restorative
      materials with antibacterial properties are desirable to help maintaining the
      residual microorganisms inactive. The adhesive system Clearfil Protect Bond (PB)
      contains the antibacterial monomer 12-methacryloyloxydodecylpyridinium bromide
      (MDPB) in its primer, which has shown antimicrobial activity. However, its
      bactericidal effect against biofilm on the dentin has been little investigated.
      OBJECTIVE: The aim of this study was to analyze by confocal laser scanning
      microscopy (CLSM) and viable bacteria counting (CFU) the MDPB bactericidal effect
      against S. mutans biofilm on the dentin surface. MATERIAL AND METHODS: Bovine
      dentin surfaces were obtained and subjected to S. mutans biofilm formation in BHI
      broth supplemented with 1% (w/v) sucrose for 18 h. Samples were divided into
      three groups, according to the primer application (n=3): Clearfil Protect Bond
      (PB), Clearfil SE Bond, which does not contain MDPB, (SE) and saline (control
      group). After the biofilm formation, Live/ Dead stain was applied directly to the
      surface of each sample. Next, 10 uL of each primer were applied on the samples
      during 590 s for the real-time CLSM analysis. The experiment was conducted in
      triplicate. The primers and saline were also applied on the other dentin samples
      during 20, 90, 300 and 590 s (n=9 for each group and period evaluated) and the
      CFU were assessed by colonies counting. RESULTS: The results of the CLSM showed
      that with the Se application, although non-viable bacteria were detected at 20 s,
      there was no increase in their count during 590 s. In contrast, after the PB
      application there was a gradual increase of non-viable bacteria over 590 s.
      CONCLUSIONS: The quantitative analysis demonstrated a significant decrease of S.
      mutans CFU at 90 s PB exposure and only after 300 s of Se application. Protect
      Bond showed an earlier antibacterial effect than Se Bond.

PMID- 23138746
TI  - Effect of a multi-layer infection control barrier on the micro-hardness of a
      composite resin.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of multiple layers of
      an infection control barrier on the micro-hardness of a composite resin. MATERIAL
      AND METHODS: One, two, four, and eight layers of an infection control barrier
      were used to cover the light guides of a high-power light emitting diode (LeD)
      light curing unit (LCU) and a low-power halogen LCU. The composite specimens were
      photopolymerized with the LCUs and the barriers, and the micro-hardness of the
      upper and lower surfaces was measured (n=10). The hardness ratio was calculated
      by dividing the bottom surface hardness of the experimental groups by the
      irradiated surface hardness of the control groups. The data was analyzed by two
      way ANOVA and Tukey's HSD test. RESULTS: The micro-hardness of the composite
      specimens photopolymerized with the LED LCU decreased significantly in the four-
      and eight-layer groups of the upper surface and in the two-, four-, and eight
      layer groups of the lower surface. The hardness ratio of the composite specimens
      was <80% in the eight-layer group. The micro-hardness of the composite specimens
      photopolymerized with the halogen LCU decreased significantly in the eight-layer
      group of the upper surface and in the two-, four-, and eight-layer groups of the
      lower surface. However, the hardness ratios of all the composite specimens
      photopolymerized with barriers were <80%. CONCLUSIONS: The two-layer infection
      control barrier could be used on high-power LCUs without decreasing the surface
      hardness of the composite resin. However, when using an infection control barrier
      on the low-power LCUs, attention should be paid so as not to sacrifice the
      polymerization efficiency.

PMID- 23138747
TI  - Micro-leakage at the implant-abutment interface with different tightening torques
      in vitro.
AB  - OBJECTIVES: This study evaluated the microleakage at the implant/abutment
      interface of external hexagon (eH) implants and abutments with different amounts
      of bacteria and tightening torques. MATERIAL AND METHODS: A bacterial suspension
      was prepared to inoculate the implants. The first phase of this study used nine
      EH implants and abutments that were divided into three groups with different
      amounts of bacterial suspension (n=3): V0.5: 0.5 uL; V1.0: 1.0 uL e V1.5: 1.5 uL,
      and tightened to the manufacturer's recommended torque. The second phase of this
      experiment used 27 assemblies that were similar to those used in the first phase.
      These samples were inoculated with 0.5 uL of bacterial suspension and divided
      into three groups (n=9). T10: 10 Ncm; T20: 20 Ncm and T32: 32 Ncm. The samples
      were evaluated according to the turbidity of the broth every 24 hours for 14
      days, and the bacteria viability was tested after that period. The statistical
      evaluation was conducted by Kruskal-Wallis testing (p<.05). RESULTS: During the
      first phase, groups V1.0 and V1.5 was presented with bacterial contamination in
      all samples after 24 h. During the second phase, two samples from group T10 and
      one from T20 presented positive results for bacterial contamination. Different
      amounts of bacterial solution led to overflow and contamination during the first
      24 h of the experiment. The tightening torques did not statistically affect the
      microleakage in the assemblies. However, the group that was tightened to 32 Ncm
      torque did not show any bacterial contamination. CONCLUSION: After 14 days of
      experimentation, the bacteria were proven to remain viable inside the implant
      internal cavity.

PMID- 23138748
TI  - Linear dimensional change, compressive strength and detail reproduction in type
      IV dental stone dried at room temperature and in a microwave oven.
AB  - The type IV dental stone is widely used for the fabrication of dyes and master
      casts for fixed and removable partial prostheses. It is typically normal to wait
      at least 24 hours for the casts to dry prior to beginning the laboratory
      procedures. The waiting time has been shown to be greatly reduced by using
      microwave drying. OBJECTIVE: This study evaluated the influence of drying
      techniques at room temperature and microwave oven on the linear dimensional
      change, compressive strength and detail reproduction in type IV dental stones.
      MATERIAL AND METHODS: Three type IV dental stone brands were selected; elite
      Rock, Shera Premium and Durone IV. Two different drying protocols were tested in
      4 groups (n=10); G-room temperature (25+/-4 oC) dried for 2 hours; G2--room
      temperature dried for 24 hours; G3-room temperature dried for 7 days and G4-
      microwave oven dried at 800 W for 5 minutes and after 2 hours at room
      temperature. After drying, the samples were assayed for dimensional charges. The
      sample surface was submitted to the ImageTool 3.0 software for compressive
      strength in a universal testing machine with a cell load of 50 KN at a crosshead
      speed of 0.5 mm/minutes and the detail reproduction was analyzed with a
      stereomicroscope at 25x magnification. The statistical analysis of the linear
      dimensional change and compressive strength data were conducted by the ANOVA test
      followed by the Tukey test (p<0.05). Detailed reproduction values were reported
      in percentages. RESULTS: For the compressive strength test, Elite Rock and Durone
      IV did not present significant differences between G2 and G4, while Shera Premium
      did not present differences between G3 and G4. The best reproduction levels were
      observed for G3. CONCLUSIONS: Dental stone microwave oven drying showed a linear
      dimensional change similar to after room temperature drying for 24 hours and 7
      days. The compressive strength of the stone dried in the microwave oven was
      similar to those dried at room temperature for 24 hours, with the exception of
      Shera Premium, which had similar results for microwave and room temperature
      drying for 7 days. For the microwave drying method the detail reproduction levels
      for samples dried at room temperature for 24 hours and 7 days were similar,
      except for the Durone IV.

PMID- 23138749
TI  - Targeted delivery of biodegradable nanoparticles with ultrasound-targeted
      microbubble destruction-mediated hVEGF-siRNA transfection in human PC-3 cells in
      vitro.
AB  - A potentially viable approach for treating late-stage prostate cancer is gene
      therapy. Successful gene therapy requires safe and efficient delivery systems. In
      this study, we report the efficient delivery of small interfering RNA (siRNA) via
      the use of biodegradable nanoparticles (NPs) made from monomethoxypoly(ethylene
      glycol)-poly(lactic-co-glycolic acid)-poly-l-lysine (mPEG-PLGA-PLL) triblock
      copolymers. On the basis of previous findings, cyclic Arg-Gly-Asp (cRGD) peptides
      were conjugated to NPs to recognize the target site, integrin alphavbeta3,
      expressed in high levels in PC-3 prostate cancer cells. The suppression of
      angiogenesis by the downregulation of vascular endothelial growth factor (VEGF)
      expression has been widely used to inhibit the growth of malignant tumors. In our
      study, human VEGF (hVEGF)-siRNA was encapsulated in NPs to inhibit VEGF
      expression in PC-3 cells. Concurrently, sonoporation induced by ultrasound
      targeted microbubble destruction (UTMD) was utilized for the delivery of siRNA
      loaded NPs. Our results showed low cytotoxicity and high gene transfection
      efficiency, demonstrating that the targeted delivery of biodegradable NPs with
      UTMD may be potentially applied as new vector system for gene delivery.

PMID- 23138750
TI  - An 11-year review of dental injuries associated with maxillofacial fractures in
      Turin, Italy.
AB  - INTRODUCTION: The aim of the study was to analyze the incidence, characteristics,
      and correlations between maxillofacial fractures and dental injuries in patients
      who were treated at a first-level trauma center in a metropolitan center in
      northwest Italy in the last 11 years. MATERIAL AND METHODS: Between January 1,
      2001 and December 31, 2011, 2,110 patients with maxillofacial fractures were
      admitted. Only dentulous patients with complete clinical records who presented
      with associated dental injuries were included in this study. Data on the age,
      gender, mechanism of injury, damaged tooth, type of dental injury, site of facial
      fractures, and concomitant injuries were recorded. RESULTS: On the whole, 267
      patients (13.1%), mainly males aged 20-29 years, presented with 759 dental
      injuries associated with maxillofacial fractures, especially following motor
      vehicle accidents. The maxillary teeth, most often the anterior elements with
      decreasing involvement from the incisors to the molars, were the teeth most
      frequently damaged overall. The main types of dental trauma in patients with
      maxillofacial fractures were luxations and dental fractures. DISCUSSION: Our
      findings show that patients with mandibular fractures were statistically and
      significantly associated with dental injury, and the teeth in the upper jaw were
      the most frequently injured teeth, exhibiting mainly luxations and crown
      fractures. Confirmation of the predominant impact site in patients with dental
      injuries associated with maxillofacial fractures comes from the 177 lacerations
      noted in the chin and lip regions in 267 patients.

PMID- 23138753
TI  - The microelectronic wireless nitrate sensor network for environmental water
      monitoring.
AB  - Quantitative monitoring of water conditions in a field is a critical ability for
      environmental science studies. We report the design, fabrication and testing of a
      low cost, miniaturized and sensitive electrochemical based nitrate sensor for
      quantitative determination of nitrate concentrations in water samples. We have
      presented detailed analysis for the nitrate detection results using the
      miniaturized sensor. We have also demonstrated the integration of the sensor to a
      wireless network and carried out field water testing using the sensor. We
      envision that the field implementation of the wireless water sensor network will
      enable "smart farming" and "smart environmental monitoring".

PMID- 23138752
TI  - Clinical application of massively parallel sequencing-based prenatal noninvasive
      fetal trisomy test for trisomies 21 and 18 in 11,105 pregnancies with mixed risk
      factors.
AB  - OBJECTIVE: To report the performance of massively parallel sequencing (MPS) based
      prenatal noninvasive fetal trisomy test based on cell-free DNA sequencing from
      maternal plasma in a routine clinical setting in China. METHOD: The MPS-based
      test was offered as a prenatal screening test for trisomies 21 and 18 to pregnant
      women in 49 medical centers over 2 years. A total of 11,263 participants were
      recruited and the MPS-based test was performed in 11,105 pregnancies. Fetal
      outcome data were obtained after the expected date of confinement. RESULTS: One
      hundred ninety cases were classified as positive, including 143 cases of trisomy
      21 and 47 cases of trisomy 18. With the karyotyping results and the feedback of
      fetal outcome data, we observed one false positive case of trisomy 21, one false
      positive case of trisomy 18 and no false negative cases, indicating 100%
      sensitivity and 99.96% specificity for the detection of trisomies 21 and 18.
      CONCLUSION: Our large-scale multicenter study proved that the MPS-based test is
      of high sensitivity and specificity in detecting fetal trisomies 21 and 18. The
      introduction of this screening test into a routine clinical setting could avoid
      about 98% of invasive prenatal diagnostic procedures.

PMID- 23138754
TI  - Fetal lower urinary tract obstruction and its management.
AB  - INTRODUCTION: Prenatal counselling in case of fetal obstructive uropathies still
      represents a clinical dilemma, despite ultrasound detection of lower urinary
      tract obstruction has greatly advanced during recent years as well as fetal
      intervention techniques. MATERIALS AND METHODS: A systematic review of the
      relevant literature on the topic was performed, with a special focus on the role
      of antenatal ultrasound, in utero treatment and prognosis. CONCLUSIONS: A clinico
      diagnostic flow chart was developed, with the specific aim of aiding health care
      givers in the clinical management and the parental decision-making process.

PMID- 23138755
TI  - The obstetric dilemma: an ancient game of Russian roulette, or a variable dilemma
      sensitive to ecology?
AB  - The difficult birth process of humans, often described as the "obstetric
      dilemma," is commonly assumed to reflect antagonistic selective pressures
      favoring neonatal encephalization and maternal bipedal locomotion. However,
      cephalo-pelvic disproportion is not exclusive to humans, and is present in some
      primate species of smaller body size. The fossil record indicates mosaic
      evolution of the obstetric dilemma, involving a number of different evolutionary
      processes, and it appears to have shifted in magnitude between Australopithecus,
      Pleistocene Homo, and recent human populations. Most attention to date has
      focused on its generic nature, rather than on its variability between
      populations. We re-evaluate the nature of the human obstetric dilemma using
      updated hominin and primate literature, and then consider the contribution of
      phenotypic plasticity to variability in its magnitude. Both maternal pelvic
      dimensions and fetal growth patterns are sensitive to ecological factors such as
      diet and the thermal environment. Neonatal head girth has low plasticity, whereas
      neonatal mass and maternal stature have higher plasticity. Secular trends in body
      size may therefore exacerbate or decrease the obstetric dilemma. The emergence of
      agriculture may have exacerbated the dilemma, by decreasing maternal stature and
      increasing neonatal growth and adiposity due to dietary shifts. Paleodemographic
      comparisons between foragers and agriculturalists suggest that foragers have
      considerably lower rates of perinatal mortality. In contemporary populations,
      maternal stature remains strongly associated with perinatal mortality in many
      populations. Long-term improvements in nutrition across future generations may
      relieve the dilemma, but in the meantime, variability in its magnitude is likely
      to persist.

PMID- 23138756
TI  - The changing face of pediatric hypertension in the era of the childhood obesity
      epidemic.
AB  - Historically, hypertension in childhood was thought to be an uncommon diagnosis,
      usually related to an underlying condition, most often parenchymal renal disease.
      Primary hypertension in childhood was felt to be quite rare. However, the
      worldwide childhood obesity epidemic has had a profound impact on the frequency
      of hypertension and other obesity-related conditions with the result that primary
      hypertension should now be viewed as one of the most common health conditions in
      the young. This review will present updated data on the prevalence of
      hypertension in children and adolescents, the impact of the childhood obesity
      epidemic on hypertension prevalence and blood pressure levels, shifts in how
      often primary hypertension is being diagnosed in childhood, and an overview of
      the pathophysiology of obesity-related hypertension. It is hoped that improved
      understanding of the significance of these issues will lead to improved
      recognition and treatment, which will be the key to averting an epidemic of
      cardiovascular disease in adulthood.

PMID- 23138758
TI  - Rational epitope design for protein targeting.
AB  - We present a new multidisciplinary strategy integrating computational biology
      with high-throughput microarray analysis aimed to translate molecular
      understanding of protein-antibody recognition into the design of efficient and
      selective protein-based analytical and diagnostic tools. The structures of two
      proteins with different folds and secondary structure contents, namely, the beta
      barrel FABP and the alpha-helical S100B, were used as the basis for the
      prediction and design of potential antibody-binding epitopes using the recently
      developed MLCE computational method. Starting from the idea that the structure,
      dynamics, and stability of a protein-antigen play a key role in the interaction
      with antibodies, MLCE integrates the analysis of the dynamical and energetic
      properties of proteins to identify nonoptimized, low-intensity energetic
      interaction-networks on the surface of the isolated antigens, which correspond to
      substructures that can aptly be recognized by a binding partner. The identified
      epitopes were next synthesized as free peptides and used to elicit specific
      antibodies in rabbits. Importantly, the resulting antibodies were proven to
      specifically and selectively recognize the original, full-length proteins in
      microarray-based tests. Competition experiments further demonstrated the
      specificity of the molecular recognition between the target immobilized proteins
      and the generated antibodies. Our integrated computational and microarray-based
      results demonstrate the possibility to rationally discover and design synthetic
      epitopes able to elicit antibodies specific for full-length proteins starting
      only from three-dimensional structural information on the target. We discuss
      implications for diagnosis and vaccine development purposes.

PMID- 23138759
TI  - Does patient gender impact resident physicians' approach to the cardiac exam?
AB  - BACKGROUND: Physical examination remains an important part of the initial
      evaluation of patients presenting with chest pain but little is known about the
      effect of patient gender on physician performance of the cardiovascular exam.
      OBJECTIVE: To determine if resident physicians are less likely to perform five
      key components of the cardiovascular exam on female versus male standardized
      patients (SPs) presenting with acute chest pain. DESIGN: Videotape review of SP
      encounters during Objective Structured Clinical Examinations (OSCEs) administered
      by the Emory University Internal Medicine Residency Program in 2006 and 2007.
      Encounters were reviewed to assess residents' performance of five cardiac exam
      skills: auscultation of the aortic, pulmonic, tricuspid, and mitral valve areas
      and palpation for the apical impulse. PARTICIPANTS: One hundred forty-nine
      incoming residents. MAIN MEASURES: Residents' performance for each skill was
      classified as correct, incorrect, or unknown. KEY RESULTS: One hundred ten of 149
      (74 %) of encounters were available for review. Residents were less likely to
      correctly perform each of the five skills on female versus male SPs. This
      difference was statistically significant for auscultation of the tricuspid (p =
      0.004, RR = 0.62, 95 % CI 0.46-0.83) and mitral (p = 0.007, RR = 0.58, 95 % CI =
      0.41-0.83) valve regions and palpation for the apical impulse (p < 0.001, RR =
      0.27, 95 % CI = 0.16-0.47). Male residents were less likely than female residents
      to correctly perform each maneuver on female versus male SPs. The interaction of
      SP gender and resident gender was statistically significant for auscultation of
      the mitral valve region (p = 0.006) and palpation for the apical impulse (p =
      0.01). CONCLUSIONS: We observed significant differences in the performance of key
      elements of the cardiac exam for female versus male SPs presenting with chest
      pain. This observation represents a previously unidentified but potentially
      important source of gender bias in the evaluation of patients presenting with
      cardiovascular complaints.

PMID- 23138760
TI  - Integrating depression care: the time has come.

PMID- 23138761
TI  - Nanosheet-constructed porous BiOCl with dominant {001} facets for superior
      photosensitized degradation.
AB  - Porous BiOCl micro-flowers constructed from ultrathin nanosheets with nearly 100%
      {001} facets exposed were selectively prepared. The exposed {001} facets
      terminated with a high density of oxygen atoms and are not only favorable for the
      adsorption of the cationic dye RhB but also can accumulate the photogenerated
      electrons injected from excited RhB. These electrons can be captured by O(2) and
      transformed to reactive oxygen species, which possess a strong photooxidative
      ability to degrade the dye pollutants directly and easily. Therefore, the
      resultant BiOCl photocatalysts exhibit superior activity for indirect dye
      photosensitization degradation under visible light, with a rapid degradation rate
      and high photostability.

PMID- 23138757
TI  - Systems genetics in "-omics" era: current and future development.
AB  - The systems genetics is an emerging discipline that integrates high-throughput
      expression profiling technology and systems biology approaches for revealing the
      molecular mechanism of complex traits, and will improve our understanding of gene
      functions in the biochemical pathway and genetic interactions between biological
      molecules. With the rapid advances of microarray analysis technologies,
      bioinformatics is extensively used in the studies of gene functions, SNP-SNP
      genetic interactions, LD block-block interactions, miRNA-mRNA interactions, DNA
      protein interactions, protein-protein interactions, and functional mapping for LD
      blocks. Based on bioinformatics panel, which can integrate "-omics" datasets to
      extract systems knowledge and useful information for explaining the molecular
      mechanism of complex traits, systems genetics is all about to enhance our
      understanding of biological processes. Systems biology has provided systems level
      recognition of various biological phenomena, and constructed the scientific
      background for the development of systems genetics. In addition, the next
      generation sequencing technology and post-genome wide association studies empower
      the discovery of new gene and rare variants. The integration of different
      strategies will help to propose novel hypothesis and perfect the theoretical
      framework of systems genetics, which will make contribution to the future
      development of systems genetics, and open up a whole new area of genetics.

PMID- 23138762
TI  - The language profile of posterior cortical atrophy.
AB  - BACKGROUND: Posterior cortical atrophy (PCA) is typically considered to be a
      visual syndrome, primarily characterised by progressive impairment of
      visuoperceptual and visuospatial skills. However, patients commonly describe
      early difficulties with word retrieval. This paper details the first systematic
      analysis of linguistic function in PCA. Characterising and quantifying the
      aphasia associated with PCA is important for clarifying diagnostic and selection
      criteria for clinical and research studies. METHODS: 15 patients with PCA, seven
      patients with logopenic/phonological aphasia (LPA) and 18 age matched healthy
      participants completed a detailed battery of linguistic tests evaluating auditory
      input processing, repetition and working memory, lexical and grammatical
      comprehension, single word retrieval and fluency, and spontaneous speech.
      RESULTS: Relative to healthy controls, PCA patients exhibited language
      impairments across all of the domains examined, but with anomia, reduced phonemic
      fluency and slowed speech rate the most prominent deficits. PCA performance most
      closely resembled that of LPA patients on tests of auditory input processing,
      repetition and digit span, but was relatively stronger on tasks of comprehension
      and spontaneous speech. CONCLUSIONS: The study demonstrates that in addition to
      the well reported degradation of vision, literacy and numeracy, PCA is
      characterised by progressive oral language dysfunction with prominent word
      retrieval difficulties. Overlap in the linguistic profiles of PCA and LPA, which
      are both most commonly caused by Alzheimer's disease, further emphasises the
      notion of a phenotypic continuum between typical and atypical manifestations of
      the disease. Clarifying the boundaries between Alzheimer's disease phenotypes has
      important implications for diagnosis, clinical trial recruitment and
      investigations into biological factors driving phenotypic heterogeneity in
      Alzheimer's disease. Rehabilitation strategies to ameliorate the phonological
      deficit in PCA are required.

PMID- 23138763
TI  - Clinical features of CIDP with LM1-associated antibodies.
AB  - BACKGROUND: LM1 is the predominant glycolipid in human peripheral nerve myelin
      and antibodies to LM1 and LM1-containing ganglioside complexes are detected in
      some patients with chronic inflammatory demyelinating polyneuropathy (CIDP). The
      clinical features of patients with such antibodies have not yet been
      investigated. METHODS: Serum antibodies to LM1, a mixture of GM1 and LM1
      (GM1/LM1), and that of GD1b and LM1 (GD1b/LM1) were examined in 75 consecutive
      patients with CIDP. The clinical features of the CIDP patients with such
      antibodies in the present series and those in the previous reports were
      investigated and compared with those of antibody-negative patients. RESULTS: Of
      the 75 patients with CIDP, two had antibodies to LM1, three had anti-GM1/LM1
      complex antibody, one had anti-GD1b/LM1 complex antibody and two had antibodies
      to both the GM1/LM1 and GD1b/LM1 complexes. Patients with the LM1-associated
      antibodies did not have cranial nerve deficits (p<0.05) and exhibited ataxia more
      frequently than the antibody-negative patients (p<0.01). CONCLUSION: In humans,
      LM1 is contained more in the dorsal root than in the cranial nerves. The clinical
      features of CIDP patients with antibodies to LM1 and LM1-containing complexes may
      be associated with the distribution of the LM1 antigen. LM1-associated antibodies
      are possible markers for a subclass of CIDP.

PMID- 23138764
TI  - Ubiquilin 2 mutations in Italian patients with amyotrophic lateral sclerosis and
      frontotemporal dementia.
AB  - OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease
      mainly involving cortical and spinal motor neurones. Molecular studies have
      recently identified different mutations in the  ubiquilin-2 (UBQLN2) gene as
      causative of a familial form of X-linked ALS, 90% penetrant in women. The aim of
      our study was to analyse the UBQLN2 gene in a large cohort of patients with
      familial (FALS) and sporadic (SALS) amyotrophic lateral sclerosis, with or
      without frontotemporal dementia (FTD), and in patients with FTD. METHODS: We
      analysed the UBQLN2 gene in 819 SALS cases, 226 FALS cases, 53 ALS-FTD patients,
      and 63 patients with a clinical record of FTD. Molecular analysis of the entire
      coding sequence was carried out in all FALS and ALS-FTD patients, while SALS and
      FTD patients were analysed specifically for the genomic region coding for the PXX
      repeat tract. Healthy controls were 845 anonymous blood donors and were screened
      for the PXX repeat region only. RESULTS: We found five different variants in the
      UBQLN2 gene in five unrelated ALS patients. Three variants, including two novel
      ones, involved a proline residue in the PXX repeat region and were found in three
      FALS cases. The other two were novel variants, identified in one FALS and one
      SALS patient. None of these variants was present in controls, while one control
      carried a new heterozygous variant. CONCLUSIONS: Our data support the role of the
      UBQLN2 gene in the pathogenesis of FALS, being conversely a rare genetic cause in
      SALS even when complicated by FTD.

PMID- 23138765
TI  - Flavour identification in frontotemporal lobar degeneration.
AB  - BACKGROUND: Deficits of flavour processing may be clinically important in
      frontotemporal lobar degeneration (FTLD). OBJECTIVE: To examine flavour
      processing in FTLD. METHODS: We studied flavour identification prospectively in
      25 patients with FTLD (12 with behavioural variant frontotemporal dementia
      (bvFTD), eight with semantic variant primary progressive aphasia (svPPA), five
      with non-fluent variant primary progressive aphasia (nfvPPA)) and 17 healthy
      control subjects, using a new test based on cross-modal matching of flavours to
      words and pictures. All subjects completed a general neuropsychological
      assessment, and odour identification was also assessed using a modified
      University of Pennsylvania Smell Identification Test. Brain MRI volumes from the
      patient cohort were analysed using voxel-based morphometry to identify regional
      grey matter associations of flavour identification. RESULTS: Relative to the
      healthy control group, the bvFTD and svPPA subgroups showed significant (p<0.05)
      deficits of flavour identification and all three FTLD subgroups showed deficits
      of odour identification. Flavour identification performance did not differ
      significantly between the FTLD syndromic subgroups. Flavour identification
      performance in the combined FTLD cohort was significantly (p<0.05 after multiple
      comparisons correction) associated with grey matter volume in the left entorhinal
      cortex, hippocampus, parahippocampal gyrus and temporal pole. CONCLUSIONS:
      Certain FTLD syndromes are associated with impaired flavour identification and
      this is underpinned by grey matter atrophy in an anteromedial temporal lobe
      network. These findings may have implications for our understanding of abnormal
      eating behaviour in these diseases.

PMID- 23138767
TI  - Neurological picture. Unilateral carpal tunnel syndrome secondary to lipomatosis
      of the median nerve.

PMID- 23138766
TI  - Transcranial direct current stimulation (tDCS) and language.
AB  - Transcranial direct current stimulation (tDCS), a non-invasive neuromodulation
      technique inducing prolonged brain excitability changes and promoting cerebral
      plasticity, is a promising option for neurorehabilitation. Here, we review
      progress in research on tDCS and language functions and on the potential role of
      tDCS in the treatment of post-stroke aphasia. Currently available data suggest
      that tDCS over language-related brain areas can modulate linguistic abilities in
      healthy individuals and can improve language performance in patients with
      aphasia. Whether the results obtained in experimental conditions are functionally
      important for the quality of life of patients and their caregivers remains
      unclear. Despite the fact that important variables are yet to be determined, tDCS
      combined with rehabilitation techniques seems a promising therapeutic option for
      aphasia. 

PMID- 23138768
TI  - Neurological pictures: neurotoxic cerebral oedema following coronary angiography.

PMID- 23138769
TI  - Efficacy of mitoxantrone in neuromyelitis optica spectrum: clinical and
      neuroradiological study.
AB  - OBJECTIVE: To evaluate the efficacy of mitoxantrone (MTX) on clinical and
      neuroradiological parameters of patients who had a relapse of neuromyelitis
      optica spectrum (NMOS) within the 12 previous months. METHODS: MTX (12 mg/m(2))
      combined with methylprednisolone 1 g as three monthly courses followed by three
      quarterly courses was administered during an observational multicentre open study
      including 51 consecutive patients (28 NMO, 23 limited forms of NMO) of the French
      Caribbean and Guyana. The main outcome measure was the reduction of the
      annualised relapse rate (ARR), and the secondary outcome measures were alteration
      of disability measured by expanded disability status scale (EDSS) score, the time
      to onset of the first relapse, and the progression of neuroradiological lesions
      at 1 year of treatment. RESULTS: At 1 year of treatment, the ARR dropped from
      1.82 to 0.37 (p<0.0001). The mean EDSS score improved by 1.3 points, going from
      5.8 at baseline to 4.5 at 1 year (p<0.0001). The number of patients showing
      gadolinium (Gad)+ spinal cord lesions at baseline, that is, 46.9%, dropped to
      10.6% (a 77.4% reduction; p=0.02). The median time to onset of the first relapse
      was 18 months. IgG-NMO seropositivity was a predictive factor of relapse
      (p=0.006). A case of acute myeloid leukaemia was observed after a mean time span
      of 4.8 years. CONCLUSIONS: In this observational NMO study, MTX decreased
      dramatically the frequency of relapses, which is directly related to progression
      of disability or even death in this disorder.

PMID- 23138770
TI  - Stent usage in the treatment of intracranial aneurysms: past, present and future.
AB  - As endovascular approaches to intracranial aneurysm (IA) treatment continue to
      evolve, the use of intracranial stents has advanced from an infrequent adjunct to
      potential curative monotherapy. Early results of endovascular therapy for IAs
      have clearly underscored large aneurysm size, low coil packing density and wide
      aneurysm neck as factors limiting successful long term obliteration. Intracranial
      stents were originally introduced as adjuncts to mitigate these limitations by
      facilitating tighter coil packing and preventing coil herniation. As evidence of
      their utility as flow diversion devices and as catalysts for aneurysm neck
      remodeling surfaced, their potential as standalone therapy was realised and is
      currently under close scrutiny. Here we review the evolution of stents in the
      treatment of IAs, from balloon expandable stents, to self-expanding stents, to
      the exciting advances in monotherapeutic flow diverting stents, amalgamating
      occlusion rates and reviewing complication rates.

PMID- 23138771
TI  - Why, for once, is the UK leading the way in implementing evidence?

PMID- 23138773
TI  - A validated survival score for breast cancer patients with metastatic spinal cord
      compression.
AB  - BACKGROUND: To create a validated scoring system predicting survival of breast
      cancer patients with metastatic spinal cord compression (MSCC). PATIENTS AND
      METHODS: Of 510 patients, one half were assigned to either the test or the
      validation group. In the test group, eight pretreatment factors (age, performance
      status, number of involved vertebrae, ambulatory status, other bone metastases,
      visceral metastases, interval from cancer diagnosis to radiotherapy of MSCC, time
      of developing motor deficits) plus the radiation regimen were retrospectively
      investigated. Factors significantly associated with survival in the multivariate
      analysis were included in the scoring system. The score for each factor was
      determined by dividing the 6-month survival rate (%) by ten. The total score was
      the sum of the scores for each factor. RESULTS: In the multivariate analysis of
      the test group, performance status, ambulatory status, other bone metastases,
      visceral metastases, interval from cancer diagnosis to radiotherapy of MSCC, and
      time of developing motor deficits were significant for survival and included in
      the score. Total scores ranged from 30 to 50 points. In the test group, the 6
      month survival rates were 12% for 30-35 points, 41% for 36-40 points, 74% for 41
      45 points, and 98% for 46-50 points (p < 0.0001). In the validation group, the 6
      month survival rates were 14%, 46%, 77%, and 99%, respectively (p < 0.0001).
      CONCLUSION: The survival rates of the validation group were similar to the test
      group. Therefore, this score was reproducible and can help when selecting the
      appropriate radiotherapy regimen for each patient taking into account her
      survival prognosis.

PMID- 23138774
TI  - Clinical evaluation of a commercial surface-imaging system for patient
      positioning in radiotherapy.
AB  - BACKGROUND: Laser scanning-based patient surface positioning and surveillance may
      complement image-guided radiotherapy (IGRT) as a nonradiation-based approach. We
      investigated the performance of an optical system compared to standard
      kilovoltage cone-beam computed tomography (CBCT) and its potential to reduce the
      number of daily CBCTs. PATIENTS AND METHODS: We analyzed the patient positioning
      of 153 treatment fractions in 21 patients applied to three different treatment
      regions. Patients were first scanned with CBCT, shifted to the optimal isocenter
      position, and an optical scan was performed to verify the matching in relation to
      CBCT. RESULTS: For the head-and-neck region, the
      lateral/longitudinal/vertical/rotational/roll and pitch shift was 0.9 +/- 1.8 mm/
      2.7 +/- 3.8 mm/-0.8 +/- 3.6 mm/0.0 +/- 1.1 degrees /-0.5 +/- 2.1 degrees /0.2 +/-
      1.6 degrees . For the thorax, the lateral/longitudinal/vertical/roll and pitch
      shift was -1.2 +/- 3.6 mm/0.8 +/- 5.1 mm/0.8 +/- 4.3 mm/0.6 +/- 1.4 degrees /0.1
      +/- 0.9 degrees /0.3 +/- 1.0 degrees . For the pelvis, the respective values were
      -2.5 +/- 4.1 mm/4.6 +/- 7.3 mm/-5.1 +/- 7.4 mm/0.3 +/- 1.1 degrees /-0.5 +/- 1.0
      degrees /0.3 +/- 2.1 degrees . In total, the recorded disagreement was -1.0 +/-
      3.6 mm/1.0 +/- 6.3 mm/-1.8 +/- 5.9 mm/0.3 +/- 1.2 degrees /-0.3 +/- 1.5 degrees
      /0.2 +/- 1.7 degrees . CONCLUSION: This analysis showed good agreement between
      the optical scanner approach and CBCT. The optical system holds potential to
      ensure precise patient positioning and reduced CBCT frequency in tumor locations
      with fixed relation to surface structures.

PMID- 23138775
TI  - [Adjuvant radiotherapy following lymphadenectomy for malignant melanoma
      significantly improves local control].

PMID- 23138776
TI  - Haplotypes in the 5'-untranslated region of the CYP1A2 gene are inversely
      associated with lung cancer risk but do not correlate with caffeine metabolism.
AB  - In this study, we analyzed the influence of CYP1A2 genetic variation and enzyme
      activity on lung cancer risk in a high-incidence area. A total of 95 lung cancer
      patients and 196 controls were genotyped for the -3860G/A, -3113A/G, -2467T/delT,
      -739T/G, and -163C/A polymorphisms in the 5'-untranslated region of the gene. In
      addition, a subset of 70 patients and 115 controls were phenotyped by high
      performance liquid chromatography determination of the caffeine metabolic ratio
      (CMR). The -2467T/delT polymorphism and the CYP1A2*1V haplotype (-163C>A, 
      2467T>delT) were inversely associated with lung cancer risk (odds ratio [OR] =
      0.47 [0.2-0.9]; P = 0.02 and OR = 0.13 [0.02-1.0]; P = 0.04; respectively). In
      addition, the CYP*1A/*1V and *1F (-163C>A)/*1D (-163C>A, -2467T>delT) diplotypes
      were absent in the patients group, whereas accounting for 7.1% (P = 0.017) and
      5.6% (P = 0.037) of controls, respectively. Mean CMR was significantly higher in
      patients than in controls (10.50 +/- 17.31 vs. 6.52 +/- 6.26, P = 0.01) but
      regression analyses did not yield significant ORs for the association with lung
      cancer risk. Similarly, no significant correlations were found between any
      genetic variant and enzyme activity. Several CYP1A2 haplotypes and diplotypes
      containing the -2467delT variant were associated with lower lung cancer risk;
      however, they did not correlate with significant changes in CYP1A2 metabolic
      activity toward caffeine.

PMID- 23138777
TI  - Translational mechanisms at work in the cohesinopathies.
AB  - Chromosome cohesion, mediated by the cohesin complex, is essential for the
      process of chromosome segregation. Mutations in cohesin and its regulators are
      associated with a group of human diseases known as the cohesinopathies. These
      diseases are characterized by defects in head, face, limb, and heart development,
      mental retardation, and poor growth. The developmental features of the diseases
      are not well explained by defects in chromosome segregation, but instead are
      consistent with changes in gene expression during embryogenesis. Thus a central
      question to understanding the cohesinopathies is how mutations in cohesin lead to
      changes in gene expression. One of the prevailing models is that cohesin binding
      to promoters and enhancers directly regulates transcription. I propose that in
      addition cohesin may influence gene expression via translational mechanisms. If
      true, cohesinopathies may be related in etiology to another group of human
      diseases known as ribosomopathies, diseases caused by defects in ribosome
      biogenesis. By considering this possibility we can more fully evaluate causes and
      treatments for the cohesinopathies.

PMID- 23138779
TI  - Isolation and characterization of charge-tagged phenylperoxyl radicals in the gas
      phase: direct evidence for products and pathways in low temperature benzene
      oxidation.
AB  - The phenylperoxyl radical has long been accepted as a critical intermediate in
      the oxidation of benzene and an archetype for arylperoxyl radicals in combustion
      and atmospheric chemistry. Despite being central to many contemporary mechanisms
      underpinning these chemistries, reports of the direct detection or isolation of
      phenylperoxyl radicals are rare and there is little experimental evidence
      connecting this intermediate with expected product channels. We have prepared and
      isolated two charge-tagged phenyl radical models in the gas phase [i.e., 4-(N,N,N
      trimethylammonium)phenyl radical cation and 4-carboxylatophenyl radical anion]
      and observed their reactions with dioxygen by ion-trap mass spectrometry.
      Measured reaction rates show good agreement with prior reports for the neutral
      system (k(2)[(Me(3)N(+))C(6)H(4) + O(2)] = 2.8 * 10(-11) cm(3) molecule(-1) s(
      1), Phi = 4.9%; k(2)[((-)O(2)C)C(6)H(4) + O(2)] = 5.4 * 10(-11) cm(3) molecule(
      1) s(-1), Phi = 9.2%) and the resulting mass spectra provide unequivocal evidence
      for the formation of phenylperoxyl radicals. Collisional activation of isolated
      phenylperoxyl radicals reveals unimolecular decomposition by three pathways: (i)
      loss of dioxygen to reform the initial phenyl radical; (ii) loss of atomic oxygen
      yielding a phenoxyl radical; and (iii) ejection of the formyl radical to give
      cyclopentadienone. Stable isotope labeling confirms these assignments. Quantum
      chemical calculations for both charge-tagged and neutral phenylperoxyl radicals
      confirm that loss of formyl radical is accessible both thermodynamically and
      entropically and competitive with direct loss of both hydrogen atom and carbon
      dioxide.

PMID- 23138780
TI  - Looming unemployment...figures.

PMID- 23138778
TI  - 5-Carboxylcytosine is localized to euchromatic regions in the nuclei of
      follicular cells in axolotl ovary.
AB  - 5-Methylcytosine (5-mC) is an epigenetic modification associated with gene
      repression. Recent studies demonstrated that 5-mC can be enzymatically oxidised
      into 5-hydroxymethylcytosine and further into 5-formylcytosine (5-fC) and 5
      carboxylcytsine (5-caC). 5-caC has been found in embryonic stem cells and in
      mouse pre-implantation embryos but no detectable levels of this modification have
      been reported for somatic tissues to date. Whereas it has been suggested that 5
      caC can serve as an intermediate in the process of active demethylation, the
      function of this form of modified cytosine remains obscure. Here we show that 5
      caC is immunochemically detectable in somatic cells of axolotl ovary. We
      demonstrate that both 5-hmC and 5-caC are localized to the euchromatin in the
      nuclei of axolotl follicular cells with similar patterns of spatial distribution.
      Our results suggest that 5-carboxylcytosine may play a distinct functional role
      in certain biological contexts.

PMID- 23138781
TI  - Choking in perspective.

PMID- 23138782
TI  - Adequate knowledge.

PMID- 23138783
TI  - A sensible protocol.

PMID- 23138784
TI  - Hot tooth.

PMID- 23138785
TI  - Ethics of health screening.

PMID- 23138786
TI  - Interpretation consideration.

PMID- 23138791
TI  - Oldest dental filling unearthed.

PMID- 23138793
TI  - Project aims to train Buddhist nuns in oral care.

PMID- 23138795
TI  - Bleaching laws introduced on Halloween.

PMID- 23138797
TI  - The elephant in the room.
AB  - Dentistry as a profession is suffering in the economic depression, yet this is
      not reflected in academic journals, with an increase in titles, articles and the
      advertising of new products and training courses suggesting otherwise. Work for
      dentists is thinning and patients are less willing to accept the costs of
      treatment plans. Is it business as usual or is UK dentistry in denial?

PMID- 23138798
TI  - Minimal intervention dentistry: part 1. From 'compulsive' restorative dentistry
      to rational therapeutic strategies.
AB  - The concept of minimal intervention dentistry is based on all the factors that
      affect the onset and progression of disease and therefore integrates concepts of
      prevention, control and treatment. The field of minimal intervention dentistry is
      wide, including the detection of lesions as early as possible, the identification
      of risk factors (risk assessment) and the implementation of preventive strategies
      and health education for the patient. When the effects of the disease are
      present, in the form of a carious lesion, other therapeutic strategies are
      required, but in this case the least invasive solutions should be chosen, for
      example remineralisation, therapeutic sealants and restorative care aimed at
      conserving the maximum amount of sound tissue. This article aims to enlighten
      dental practitioners as to the foundations of minimal intervention dentistry in
      order to help them in the implementation of modern concepts into everyday
      clinical practice.

PMID- 23138799
TI  - Minimal intervention dentistry: part 2. Caries risk assessment in adults.
AB  - Risk-based, patient-centred decision-making, supported by best available evidence
      is an essential component for the correct prevention, control and management of
      dental caries. This article reviews the importance of caries risk assessment in
      adults as a prerequisite for appropriate caries preventive and treatment
      intervention decisions. A clinical case will be used to demonstrate how risk
      assessment can be easily incorporated in everyday clinical practice, using
      information readily available in the dental-medical history and clinical
      examination.

PMID- 23138800
TI  - Obesity and oral disease - a challenge for dentistry.
AB  - The prevalence of overweight and obesity is rising in many developed and
      developing countries and, most worryingly, among children. Within the EU,
      Scotland has the highest prevalence, more than twice that of the Netherlands, and
      in England almost a quarter of children now enter primary school either
      overweight or obese, rising to one in three on leaving at age 11 years. Whilst
      most epidemiological data is based on body mass index, this is not a reliable
      indicator of individual adiposity and morbidity risk. The association between
      excess adiposity and type 2 diabetes is well recognised and the latter carries
      implications for oral disease and dental treatment. Current research has not
      established a clear association between excess adiposity and caries prevalence,
      however, there is evidence for a higher prevalence of chronic periodontal disease
      in obese populations. There is some evidence that this is not mediated solely by
      diabetes, but by secretion by adipose tissue of chemical mediators of
      inflammation, including cytokines and hormones, which could modify the response
      of the periodontal tissues to the oral environment. Dental professionals must
      become aware of this growing problem, of the demands that the rising obesity
      prevalence will place on dental care services and the need for bariatric dental
      facilities. Together, with service providers, dental professionals must prepare
      for the challenge ahead.

PMID- 23138805
TI  - Summary of: comparing the onset of maxillary infiltration local anaesthesia and
      pain experience using the conventional technique vs the Wand in children.
AB  - AIM: This prospective, randomised, parallel, controlled study was conducted
      firstly to compare the onset of local anaesthesia (LA) when using the
      conventional technique versus the Wand computer-controlled LA and secondly to
      assess the pain experience in children. METHOD: Thirty children were randomly
      allocated to the treatment group (Wand) or the control group (conventional).
      Lidocaine 2% with adrenaline (1:80,000) was given as a buccal infiltration. The
      onset of pulpal anaesthesia was tested using an analytic electric pulp tester
      (EPT). The pain experience during the LA was recorded using a modified visual
      analogue score (VAS). RESULTS: Median time for the onset of LA was 6.30 minutes
      for the control and 7.25 minutes for the Wand group. Mean pain experience score
      for the control group was 9.78% as opposed to 8.46% in the Wand group.
      Statistical analysis showed that there was no statistically significant
      difference in the onset of LA (p = 0.486) and the pain experience (p = 0.713)
      between the two groups. CONCLUSION: When placing a buccal infiltration on upper
      first permanent molars, the onset of LA and the pain experience was no different
      using the Wand and the conventional technique.

PMID- 23138806
TI  - Summary of: prevalence of oral diseases and oral-health-related quality of life
      in people with severe mental illness undertaking community-based psychiatric
      care.
AB  - OBJECTIVES: To describe the prevalence of oral diseases and their impact on oral
      health-related quality of life in people with severe mental illness undertaking
      community-based psychiatric care. METHODS: A survey was conducted at eight
      outpatient psychiatric care clinics in Tower Hamlets, London, UK. One hundred and
      twelve consecutive patients with mental illness were invited to participate in
      this study. They were clinically examined and asked to complete the oral health
      impact profile (OHIP) questionnaire. RESULTS: The response rate was 79% (n = 89);
      57 (64%) males and 58 persons over 45 years of age (65%) participated in this
      survey. Overall OHIP score was 25.4 (95% CI 23.3, 27.4), 70 (78%) were smokers
      and 45 (51%) had been to the dentist in the last two years. Forty-seven (53%)
      respondents had caries in at least one tooth, 60 (67%) had 21 teeth and more, and
      14 (16%) used dentures. Advanced periodontal treatment was indicated in 42 (55%)
      of patients and 52.8% (n = 47) patients reported current pain. CONCLUSION:
      Overall, this survey found that oral health has a great impact on patients with
      severe mental illness being treated in the community setting and their oral
      health is poorer than the national adult general population. Future research
      should consider the causes that relate to the poorer oral health in this
      population and potential health promotion mechanisms in this population to
      encourage an upstream approach to health.

PMID- 23138807
TI  - Do I have enough time? The impact of recruiting patients to a randomised
      controlled trial at recruiting centres.
AB  - INTRODUCTION: This paper explores the impact of recruiting patients to a
      randomised controlled trial (RCT) at recruiting centres. This large multicentre
      RCT examining the efficacy of chewing gum compared to ibuprofen in the relief of
      orthodontic pain was carried out across nine recruiting centres. METHOD: The work
      diaries of clinicians and supporting staff at recruiting centres were analysed
      over a four-month period from September to December 2011. This quantified the
      amount of clinical and non-clinical time spent on research duties. RESULTS: Over
      this time period 98 patients were recruited across seven trial sites. On average,
      patient recruitment had a direct clinical impact of 19 minutes per patient
      recruited. The time commitment on trial administration outside the clinical
      sessions was much higher, averaging at 110 minutes per patient recruited, giving
      the overall time spent on the trial 129 minutes per patient. CONCLUSIONS: This
      information will be valuable to lead researchers when calculating the full
      economic cost of a proposed clinical trial and therefore when applying for grant
      funding. It may also be valuable to clinicians and their managers when
      considering becoming a principle investigator (PI) in a RCT. Although the impact
      on clinical time was 19 minutes per patient recruited, there is a considerably
      higher (almost six times greater) time commitment in administration around the
      recruitment of patients.

PMID- 23138823
TI  - Nikos Donos: peri-implantitis: is it a problem? By Ruth Doherty.

PMID- 23138830
TI  - Comparing the onset of maxillary infiltration local anaesthesia and pain
      experience using the conventional technique vs. the Wand in children.
AB  - AIM: This prospective, randomised, parallel, controlled study was conducted
      firstly to compare the onset of local anaesthesia (LA) when using the
      conventional technique versus the Wand computer-controlled LA and secondly to
      assess the pain experience in children. METHOD: Thirty children were randomly
      allocated to the treatment group (Wand) or the control group (conventional).
      Lidocaine 2% with adrenaline (1:80,000) was given as a buccal infiltration. The
      onset of pulpal anaesthesia was tested using an analytic electric pulp tester
      (EPT). The pain experience during the LA was recorded using a modified visual
      analogue score (VAS). RESULTS: Median time for the onset of LA was 6.30 minutes
      for the control and 7.25 minutes for the Wand group. Mean pain experience score
      for the control group was 9.78% as opposed to 8.46% in the Wand group.
      Statistical analysis showed that there was no statistically significant
      difference in the onset of LA (p = 0.486) and the pain experience (p = 0.713)
      between the two groups. CONCLUSION: When placing a buccal infiltration on upper
      first permanent molars, the onset of LA and the pain experience was no different
      using the Wand and the conventional technique.

PMID- 23138831
TI  - Prevalence of oral diseases and oral-health-related quality of life in people
      with severe mental illness undertaking community-based psychiatric care.
AB  - OBJECTIVES: To describe the prevalence of oral diseases and their impact on oral
      health-related quality of life in people with severe mental illness undertaking
      community-based psychiatric care. METHODS: A survey was conducted at eight
      outpatient psychiatric care clinics in Tower Hamlets, London, UK. One hundred and
      twelve consecutive patients with mental illness were invited to participate in
      this study. They were clinically examined and asked to complete the oral health
      impact profile (OHIP) questionnaire. RESULTS: The response rate was 79% (n = 89);
      57 (64%) males and 58 persons over 45 years of age (65%) participated in this
      survey. Overall OHIP score was 25.4 (95% CI 23.3, 27.4), 70 (78%) were smokers
      and 45 (51%) had been to the dentist in the last two years. Forty-seven (53%)
      respondents had caries in at least one tooth, 60 (67%) had 21 teeth and more, and
      14 (16%) used dentures. Advanced periodontal treatment was indicated in 42 (55%)
      of patients and 52.8% (n = 47) patients reported current pain. CONCLUSION:
      Overall, this survey found that oral health has a great impact on patients with
      severe mental illness being treated in the community setting and their oral
      health is poorer than the national adult general population. Future research
      should consider the causes that relate to the poorer oral health in this
      population and potential health promotion mechanisms in this population to
      encourage an upstream approach to health.

PMID- 23138832
TI  - Difficulties reducing inappropriate prescribing of proton pump inhibitors in the
      elderly.

PMID- 23138833
TI  - Comparison between the three most popular formulae to estimate renal function, in
      subjects 75 years of age or older.
AB  - OBJECTIVES: The aim of the study was to compare the accuracy of three formulae
      that estimate creatinine clearance (CL(CR)), in elderly hospitalized patients:
      the Cockcroft-Gault (CG) formula and the Modification of Diet in Renal Disease
      formulae with 4 and 6 variables (MDRD4 and MDRD6). METHODS: A prospective, cross
      sectional, observational study was conducted in four hospital geriatric wards.
      Consecutive patients admitted to the wards who were aged >=75 years and had an
      indwelling urinary catheter for the purpose of care were eligible for enrolment.
      CL(CR) was determined via four methods: measurement of CL(CR) from plasma and
      urine creatinine plus 24-h urine volume; the CG formula; and the MDRD4 and MDRD6
      formulae. Moderate and severe renal impairments were defined as a CL(CR) of 30.0
      59.9 and <30.0 mL/min, respectively. RESULTS: A total of 157 patients were
      included. Their mean age (+/-SD) was 86.5 +/- 6.1 (range 75-105) years and 46.5 %
      were male. The median values and interquartile ranges (IQRs) (in mL/min) were
      44.0 (IQR 32.1-64.5) for measured CL(CR), 42.1 (IQR 31.3-56.3) for CG-estimated
      CL(CR), 64.3 (IQR 49.8-81.7) for MDRD4-estimated CL(CR) and 49.3 (IQR 37.4-63.4)
      for MDRD6-estimated CL(CR) (respectively, p < 0.05, p < 0.001 and p = 0.44
      compared with measured CL(CR)). Biases (+/-SD) for CG, MDRD4 and MDRD6 CL(CR)
      estimates were -3.6 (+/-22.2), 19.3 (+/-26.4) and 2.4 (+/-22.5) mL/min,
      respectively. When estimated CL(CR) values were assessed against the measured
      value, it was found that misclassification of renal impairment
      (absent/moderate/severe) occurred in 41 % of patients when using the CG, in 40 %
      when using the MDRD6, and in 45 % when using the MDRD4. The 30 % accuracies of
      the three formulae were 63 % for CG, 37 % for MDRD4 and 59 % for MDRD6.
      CONCLUSION: In elderly hospitalized patients, CG and MDRD6 gave better
      predictions for measured CL(CR) than MDRD4, with no significant difference
      between them.

PMID- 23138834
TI  - The pharmacological management of post-stroke muscle spasticity.
AB  - Muscle hypertonia following upper motor neurone lesions (referred to here as
      'spasticity') is a common problem in patients with neurological disease, and its
      management is one of the major challenges in clinical practice. Understanding the
      pathogenesis and clinical course of spasticity is essential for the effective
      management of this condition. The hypertonia initially results from increased
      excitability of the alpha motor neurones due to an imbalance between the
      excitatory and inhibitory influences of the vestibulospinal and reticulospinal
      tracts. This is the 'neural component' of muscle hypertonia. However, usually
      within 3-4 weeks, changes in the structure and mechanical properties of the
      paralysed muscles and the effect of thixotropy also contribute to the hypertonia.
      The selection of the optimal treatment option is often influenced by whether the
      neural or the non-neural component is more pronounced. Muscle spasticity often
      interferes with motor function or causes distressing symptoms, such as painful
      muscle spasms. If untreated, spasticity may also lead to soft tissue shortening
      (fixed contractures). However, spasticity can also be beneficial to patients. For
      example, despite severe leg muscle weakness, most hemiplegic patients are able to
      walk because the spasticity of the extensor muscles braces the lower limb in a
      rigid pillar. Other reported benefits of spasticity include the maintenance of
      muscle bulk and bone mineral density and possibly a reduced risk of lower limb
      deep vein thrombosis. Several factors, such as skin pressure sores, faecal
      impaction, urinary tract infections and stones in the urinary bladder, can
      aggravate muscle spasticity. These factors should always be looked for as their
      adequate treatment is often sufficient to reduce muscle tone without the need for
      specific antispasticity medication. Therefore, a careful evaluation of the
      patient's symptoms and their impact on function, and the setting of clear and
      realistic therapy goals are important prerequisites to treatment. The best
      treatment outcomes are usually achieved when pharmacological and non
      pharmacological treatment modalities are used in tandem. Different drugs are
      available for the management of spasticity, including oral muscle relaxants,
      anticonvulsant drugs, intrathecal baclofen, cannabis extract, phenol and alcohol
      (for peripheral nerve blocks) and botulinum toxin injections. Similarly, there is
      a range of non-pharmacological methods of treatment, e.g. regular muscle
      stretching, the use of splints and orthoses, electrical stimulation, etc.
      Although these are not discussed here, this should not detract from the
      importance of combining them with antispasticity drugs in order to maximize the
      clinical benefit of treatment.

PMID- 23138835
TI  - Hybrid plasmonic platforms based on silica-encapsulated gold nanorods as
      effective spectroscopic enhancers for Raman and fluorescence spectroscopy.
AB  - Surface-enhanced Raman scattering (SERS) nano-tags are of increasing interest in
      biomedical research as viable alternatives to bio-imaging techniques based on
      semiconductor quantum dots or fluorescent molecules. In this work, we fabricate
      silica-coated gold nanorods (AuNRs) encoded with two molecular labels to operate
      as highly effective spectroscopic nano-tags in near-infrared SERS (NIR-SERS) and
      surface-enhanced resonance Raman scattering combined with metal-enhanced
      fluorescence (SERRS-MEF), respectively. Specifically, a non-fluorescent molecule
      with strong affinity for a gold surface (para-aminothiophenol, p-ATP) and a
      common dye (Nile Blue, NB) with lower affinity have been successfully tested as
      NIR-SERS nano-tags under laser excitation at 785 nm. Moreover, as a result of
      designing AuNRs with a plasmon resonance band overlapping the electronic
      absorption band of the encoded NB molecule, a dual SERRS and MEF performance has
      been devised under resonant excitation at 633 nm. We explain this result by
      considering a partial desorption of NB molecules from the metal surface and their
      trapping into the silica shell at favorable distances to avoid quenching and
      enhance the fluorescence signal. Finally, we prove that the silica shell prevents
      the desorption or chemical transformation of p-ATP into p,p'-dimercaptoazobenzene
      species, as previously noticed, thus providing a highly stable SERRS signal,
      which is crucial for imaging applications.

PMID- 23138836
TI  - Evaluating immunologic response and clinical deterioration in treatment-naive
      patients initiating first-line therapies infected with HIV-1 CRF01_AE and subtype
      B.
AB  - BACKGROUND: HIV-1 group M viruses diverge 25%-35% in envelope, important for
      viral attachment during infection, and 10%-15% in the pol region, under selection
      pressure from common antiretrovirals. In Asia, subtypes B and CRF01_AE are common
      genotypes. Our objectives were to determine whether clinical, immunological, or
      virological treatment responses differed by genotype in treatment-naive patients
      initiating first-line therapy. METHODS: Prospectively collected longitudinal data
      from patients in Thailand, Hong Kong, Malaysia, Japan, Taiwan, and South Korea
      were provided for analysis. Covariates included demographics, hepatitis B and C
      coinfections, baseline CD4 T lymphocyte count, and plasma HIV-1 RNA levels.
      Clinical deterioration (a new diagnosis of Centers for Disease Control and
      Prevention category B/AIDS-defining illness or death) was assessed by
      proportional hazards models. Surrogate endpoints were 12-month change in CD4 cell
      count and virologic suppression post therapy, evaluated by linear and logistic
      regression, respectively. RESULTS: Of 1105 patients, 1036 (93.8%) infected with
      CRF01_AE or subtype B were eligible for inclusion in clinical deterioration
      analyses and contributed 1546.7 person-years of follow-up (median: 413 days,
      interquartile range: 169-672 days). Patients >40 years demonstrated smaller
      immunological increases (P = 0.002) and higher risk of clinical deterioration
      (hazard ratio = 2.17; P = 0.008). Patients with baseline CD4 cell counts >200
      cells per microliter had lower risk of clinical deterioration (hazard ratio =
      0.373; P = 0.003). A total of 532 patients (48.1% of eligible) had CD4 counts
      available at baseline and 12 months post therapy for inclusion in immunolgic
      analyses. Patients infected with subtype B had larger increases in CD4 counts at
      12 months (P = 0.024). A total of 530 patients (48.0% of eligible) were included
      in virological analyses with no differences in response found between genotypes.
      CONCLUSIONS: Results suggest that patients infected with CRF01_AE have reduced
      immunologic response to therapy at 12 months, compared with subtype B-infected
      counterparts. Clinical deterioration was associated with low baseline CD4 counts
      and older age. The lack of differences in virologic outcomes suggests that all
      patients have opportunities for virological suppression.

PMID- 23138837
TI  - Genetic variants in the host restriction factor APOBEC3G are associated with HIV
      1-related disease progression and central nervous system impairment in children.
AB  - BACKGROUND: Apolipoprotein B mRNA editing catalytic polypeptide 3G (APOBEC3G)
      protein is incorporated into nascent virus particles and mediates cytidine
      deamination (C-to-U) of first-strand reverse transcripts of HIV-1 in target cells
      resulting in G-to-A hypermutation of the coding strand and premature degradation.
      We investigated the effects of APOBEC3G genetic variants on HIV-1-related disease
      in children. METHODS: APOBEC3G variants were detected using real-time polymerase
      chain reaction in HIV-1-infected children from Pediatric AIDS Clinical Trials
      Group (PACTG) protocols P152 and P300 that evaluated the effectiveness of 3 mono-
      or dual-nucleoside reverse transcriptase inhibitor treatments. RESULTS: Of the
      1049 children evaluated, 60% were non-Hispanic black, 26% Hispanic, 13% non
      Hispanic white, and 1% other or unknown race/ethnicity. Age ranged from 42 days
      to 18 years; 45% were males. APOBEC3G-H186R homozygous G/G genotype was
      associated with more rapid HIV-1 disease progression [hazard ratio (HR): 1.69; P
      = 0.01] and central nervous system (CNS) impairment (HR: 2.00; P = 0.02) compared
      with the wild-type A/A or heterozygous A/G genotype in a recessive model. In both
      additive and dominant models, APOBEC3G-F119F-C allele was associated with
      protection against disease progression (HR [additive]: 0.69; P = 0.002 and HR
      [dominant]: 0.60; P = 0.001, respectively) and CNS impairment (HR [additive]:
      0.65; P = 0.02 and HR [dominant]: 0.54; P = 0.007, respectively). These
      associations remained significant in multivariate analyses controlling for
      baseline characteristics or previously identified genetic variants known to alter
      HIV-1-related disease in this cohort of children. CONCLUSIONS: APOBEC3G-H186R and
      F119F variants are associated with altered HIV-1-related disease progression and
      CNS impairment in children.

PMID- 23138838
TI  - Design and in vitro evaluation of transdermal patches based on ibuprofen-loaded
      electrospun fiber mats.
AB  - To improve the poor compatibility among different components of Drug-in-adhesive
      type patch, two novel plasters (Drug-in-fiber and Drug-in-adhesive/fiber) were
      developed based on ibuprofen (IBU)-loaded fiber mats. These fibrous mats were
      fabricated via electrospinning of cellulose acetate/poly(vinylpyrrolidone)
      composites in a binary solvent of N,N-dimethyl acetamide/acetone. Physical status
      studies suggested that Drug-in-fiber could inhibit IBU re-crystallization, but
      the active ingredients were released at a relatively slow rate due to the dual
      resistance of fiber mat and adhesive matrix. To overcome this shortcoming, Drug
      in-adhesive/fiber was designed by coupling medicated hydrophilic pressure
      sensitive adhesive and IBU-loaded fiber mat. This method endowed Drug-in
      adhesive/fiber a fast IBU release rate and high permeated drug amount though
      simulative skins. This design separated enhancer from adhesive matrix, which
      guaranteed Drug-in-adhesive/fiber excellent adhesion forces. Hence, the plasters
      based on medicated fiber mats improved the compatibility among patch components.

PMID- 23138839
TI  - Osteoblast, fibroblast and in vivo biological response to poly(vinylidene
      fluoride) based composite materials.
AB  - Electroactive materials can be taken to advantage for the development of sensors
      and actuators as well as for novel tissue engineering strategies. Composites
      based on poly(vinylidene fluoride), PVDF, have been evaluated with respect to
      their biological response. Cell viability and proliferation were performed in
      vitro both with Mesenchymal Stem Cells differentiated to osteoblasts and Human
      Fibroblast Foreskin 1. In vivo tests were also performed using 6-week-old C57Bl/6
      mice. It was concluded that zeolite and clay composites are biocompatible
      materials promoting cell response and not showing in vivo pro-inflammatory
      effects which renders both of them attractive for biological applications and
      tissue engineering, opening interesting perspectives to development of scaffolds
      from these composites. Ferrite and silver nanoparticle composites decrease
      osteoblast cell viability and carbon nanotubes decrease fibroblast viability.
      Further, carbon nanotube composites result in a significant increase in local
      vascularization accompanied an increase of inflammatory markers after
      implantation.

PMID- 23138840
TI  - The prophylactic role of D-saccharic acid-1,4-lactone against hyperglycemia
      induced hepatic apoptosis via inhibition of both extrinsic and intrinsic pathways
      in diabetic rats.
AB  - Sustained hyperglycemia and increased oxidative stress play major roles in the
      development of secondary complications in diabetes including liver injury.
      Dietary supplement of antioxidants is effective in preventing oxidative stress
      mediated tissue damage in diabetic pathophysiology. D-Saccharic acid 1,4-lactone
      (DSL), a derivative of D-glucaric acid, is present in many dietary plants and is
      known for its detoxifying and antioxidant properties. Our early investigation
      showed that DSL can ameliorate alloxan (ALX) induced diabetes mellitus and
      oxidative stress in rats by inhibiting pancreatic beta-cell apoptosis. In the
      present study we investigated the protective role of DSL against hepatic
      dysfunction in ALX induced diabetic rats. ALX exposure elevated the blood
      glucose, serum ALP and ALT levels, the production of reactive oxygen species
      (ROS), and disturbed the intra-cellular antioxidant machineries. Oral
      administration of DSL restored all these alterations close to normal. By
      investigating the mechanism of its protective activity, we observed that DSL
      prevented hyperglycemia induced hepatic apoptosis by inhibiting both extrinsic
      and intrinsic pathways. Results showed that in the liver tissue, diabetes
      promoted a significant increase of TNF-alpha/TNF-R1 and led to the activation of
      caspase-8 and t-Bid. In addition, ALX exposure reciprocally regulated Bcl-2
      family protein expression, disturbed mitochondrial membrane potential, and
      subsequently released cytochrome c from mitochondria to cytosol. As a
      consequence, a significant increase in caspase-3 expression was observed in the
      liver of diabetic animals. However, treatment of diabetic rats with DSL
      counteracted these changes, making it a promising approach in lessening diabetes
      mediated tissue damage.

PMID- 23138841
TI  - Translation of an evidence-based asthma intervention: Physician Asthma Care
      Education (PACE) in the United States and Australia.
AB  - BACKGROUND: Physician Asthma Care Education (PACE) is a programme developed in
      the USA to improve paediatric asthma outcomes. AIMS: To examine translation of
      PACE to Australia. METHODS: The RE-AIM framework was used to assess translation.
      Demographic characteristics and findings regarding clinical asthma outcomes from
      PACE randomised clinical trials in both countries were examined. Qualitative
      content analysis was used to examine fidelity to intervention components.
      RESULTS: Both iterations of PACE reached similar target audiences (general
      practice physicians and paediatric patients with asthma); however, in the USA,
      more children with persistent disease were enrolled. In both countries,
      participation comprised approximately 10% of eligible physicians and 25% of
      patients. In both countries, PACE deployed well-known local physicians and
      behavioural scientists as facilitators. Sponsorship of the programme was provided
      by professional associations and government agencies. Fidelity to essential
      programme elements was observed, but PACE Australia workshops included additional
      components. Similar outcomes included improvements in clinician confidence in
      developing short-term and long-term care plans, prescribing inhaled
      corticosteroids, and providing written management instructions to patients. No
      additional time was spent in the patient visit compared with controls. US PACE
      realised reductions in symptoms and healthcare use, results that could not be
      confirmed in Australia because of limitations in follow-up time and sample sizes.
      US PACE is maintained through a National Heart, Lung, and Blood Institute
      website. Development of maintenance strategies for PACE Australia is underway.
      CONCLUSIONS: Based on criteria of the RE-AIM framework, the US version of PACE
      has been successfully translated for use in Australia.

PMID- 23138842
TI  - Can dietary interventions improve asthma control?

PMID- 23138843
TI  - Co-morbidity is the norm, not the exception: chronic respiratory diseases in
      chronic drug users.

PMID- 23138844
TI  - A qualitative study of patients' goals and expectations for  self-management of
      COPD.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an illness that
      affects patients on multiple levels, both physically and psychologically. While
      there is a growing body of evidence for the efficacy of self-management among
      patients with COPD, little evidence is available on the optimal content and
      methods for delivering self-management support. AIMS: The purpose of this study
      was to address gaps in the literature on self-management support by examining
      patients' responses to questions about goals, needs, and expectations regarding
      self-management using qualitative methods in a broadly representative sample of
      patients with moderate to severe COPD. By focusing on patients' perceptions of
      their needs, we hoped to guide development of cognitive-behavioural interventions
      for self-management support. METHODS: Patients >45 years of age with a physician
      diagnosis of COPD were recruited as part of a larger randomised controlled trial
      designed to determine the effectiveness of a lifestyle behavioural intervention
      to increase physical activity. In-depth interviews were conducted at baseline
      data collection using 10 standardised open-ended questions tailored to examine
      factors relevant to self-management support including concerns, fears, learning
      needs, barriers, facilitators, and goals. All interviews were audio recorded and
      analysed using qualitative methods. Responses were coded by three raters into
      thematic categories. RESULTS: A sample of 47 interviews with patients of mean age
      68.4 years, 53% male, 87% white were used in the analysis. The distribution of
      spirometric impairment based on percent predicted forced expiratory volume in 1
      second (FEV1) was moderate (57.5%), severe (31.9%), and very severe (10.6%). In
      response to questions targeting needs and goals for care, three main themes
      (loss, fear, and desire for improved care) and seven associated sub-themes were
      identified. Because of breathlessness and fatigue as well as symptoms from
      conditions other than COPD, patients reported the loss of ability to participate
      in pleasurable and necessary activities of daily living and the desire to recover
      at least some of their functioning. They expressed problems with social isolation
      and uncertainty about their prognosis, as well as the hope to improve. In
      addition, fearful experiences associated with uncontrolled breathlessness and a
      wish for greater understanding and knowledge about treatment were major concerns.
      CONCLUSIONS: These qualitative results suggest that the content of self
      management support for patients with COPD should focus on addressing patients'
      fears associated with the uncertainty, progression, and suffering of their
      disease, their expectations about overcoming or replacing losses, their needs for
      improved health literacy and their desire for improved care. These responses
      indicate areas where cognitive-behavioural intervention should focus in order to
      enhance patient self-efficacy, motivation, and behavioural change for improved
      self-management.

PMID- 23138845
TI  - Effect of uvulopalatopharyngoplasty on retropalatal region.
AB  - Flexible optic laryngoscopy (FOL) allows us to visualize the obstructive sleep
      apnea (OSA)-related airway passages. Retropalatal region is a part of upper
      airway contributing to the OSA. We aimed to demonstrate the changes in the
      retropalatal surface area (RPSA) after submucosal uvulopalatopharyngoplasty
      (smUPPP) in an attempt to exhibit enlargement as a predictor of surgical
      treatment. It is a prospective, case-control study and conducted at the
      Otolaryngology department in a university hospital. Twenty patients with OSA who
      underwent smUPPP were prospectively evaluated. Pre and postoperative respiratory
      disturbance index (RDI) and RPSA measurements were studied. Retropalatal region
      videos were obtained at the base of uvula during FOL. Photographic images were
      captured at the same level of a virtual horizontal line passing through the base
      of uvula posteriorly to measure RPSAs using AutoCad2004. RDI levels, RPSA
      measurements were compared using paired t test. Twenty patients underwent smUPPP.
      There were 17 (85 %) male and 3 (15 %) female. The mean age was 37 years. The
      RPSA measurements were between 18.41 and 144.102 (mean 63.39) preoperatively. The
      RPSA measurements were between 83.784 and 255.463 (mean 143.87) postoperatively.
      The RPSA measurements were significantly enlarged postoperatively (p < 0.0005).
      The mean RPSA increased from 63.39 +/- 29.3 to 143.82 +/- 57.8. The mean RDI
      decreased from 22.95 +/- 19.2 to 9.0 +/- 8.2 (p = 0.011). RPSA increases in
      smUPPP patients postoperatively, evidencing enlarged retropalatal region.
      Decreased RDI levels indicate amelioration in OSA. RPSA measurements can be used
      to predict UPPP surgical treatment success.

PMID- 23138846
TI  - Mitochondrial dysfunction in osteoarthritis is associated with down-regulation of
      superoxide dismutase 2.
AB  - OBJECTIVE: Superoxide dismutase 2 (SOD2) is down- regulated in osteoarthritis
      (OA). This study was undertaken to investigate the functional effects of this
      down-regulation in the context of oxidative damage and mitochondrial dysfunction.
      METHODS: Lipid peroxidation in articular cartilage from OA patients and from
      lesion-free control subjects with femoral neck fracture was assessed by measuring
      malondialdehyde levels using the thiobarbituric acid reactive substances assay.
      Long-range polymerase chain reaction amplification and a mitochondrial DNA
      (mtDNA) strand break assay were used to investigate the presence of somatic large
      scale mtDNA rearrangements in cartilage. Microscale oxygraphy was used to explore
      possible changes in mitochondrial respiratory activity between OA and control
      chondrocytes. RNA interference was used to determine the effects of SOD2
      depletion on lipid peroxidation, mtDNA damage, and mitochondrial respiration.
      RESULTS: OA cartilage had higher levels of lipid peroxidation compared to control
      cartilage, and lipid peroxidation was similarly elevated in SOD2-depleted
      chondrocytes. SOD2 depletion led to a significant increase in mtDNA strand breaks
      in chondrocytes, but there was no notable difference in the level of strand
      breaks between OA and control chondrocytes. Furthermore, only very low levels of
      somatic, large-scale mtDNA rearrangements were identified in OA cartilage. OA
      chondrocytes showed less spare respiratory capacity (SRC) and higher proton leak
      compared to control chondrocytes. SOD2-depleted chondrocytes also showed less SRC
      and higher proton leak. CONCLUSION: This is the first study to analyze the
      effects of SOD2 depletion in human articular chondrocytes in terms of changes to
      oxidation and mitochondrial function. The findings indicate that SOD2 depletion
      in chondrocytes leads to oxidative damage and mitochondrial dysfunction,
      suggesting that SOD2 down-regulation is a potential contributor to the
      pathogenesis of OA.

PMID- 23138847
TI  - Involvement of the mitochondrial pathway and Bim/Bcl-2 balance in
      dihydroartemisinin-induced apoptosis in human breast cancer in vitro.
AB  - Dihydroartemisinin (DHA), a semi-synthetic derivative and active metabolite of
      artemisinin, has been shown to have profound anticancer potential in addition to
      its strong anti-malarial activity. The purpose of the present study was to
      thoroughly investigate the anti-neoplastic effects induced by DHA and to provide
      a molecular basis for the use of DHA in the treatment of breast cancer. Our
      results demonstrated that DHA could significantly inhibit the cell proliferation
      of breast cancer in a dose- and time-dependent manner that was associated with
      induced apoptosis and G0/G1 cell cycle arrest, and the half maximal inhibitory
      concentrations (IC50) of DHA treatment were 60.03, 33.86 and 17.18 uM for 24, 48
      and 72 h, respectively. Moreover, the DHA treatment dramatically increased the
      protein expression of caspase-8, cleaved caspase-9, activated Bid and induced the
      release of cytochrome c from mitochondria into the cytosol. In addition, the
      apoptotic action of DHA was associated with the increased expression of the pro
      apoptotic gene Bim and a decreased expression of the anti-apoptotic gene Bcl-2.
      Therefore, the mitochondrial pathway is involved in the apoptosis of breast
      cancer cells induced by DHA and the imbalance of the Bim/Bcl-2 interaction may
      promote the beneficial effect against breast cancer cells. Overall, our study
      provides the scientific rationale for the clinical usage of DHA for breast
      cancer.

PMID- 23138848
TI  - Rapid aneusomy detection in products of conception using the KaryoLiteTM BACs-on
      BeadsTM assay.
AB  - OBJECTIVE: Chromosome analysis is the traditional method for detecting genetic
      abnormalities in products of conception, but it is prone to a high failure rate
      because of the requirement for cell culture. Molecular genetic tests do not
      require cell culture, but are either more expensive (e.g. chromosomal microarray)
      or less sensitive than chromosome analysis (e.g. fluorescence in situ
      hybridization, multiplex ligation mediated amplification). The KaryoLiteTM BACs
      on-BeadsTM (KL-BoBsTM) assay is highly multiplexed with low resolution coverage
      and is designed to detect aneusomy for any chromosome. METHODS: We
      retrospectively tested 100 products of conception samples previously
      characterized by karyotype (n = 90), and/or microarray (n = 61) using KL-BoBsTM.
      We included samples extracted from either cultured or direct specimens from
      placental villi or fetal somatic tissue, with a variety of chromosomal
      abnormalities typically identified in our clinical cytogenetics laboratory.
      RESULTS: KL-BoBsTM and microarray results were concordant for all cases of
      aneusomy. On the basis of a review of 3794 consecutive cases in our laboratory,
      aneusomy accounts for 74.3% of abnormalities detected. Polyploidy and structural
      abnormalities were not detected by KL-BoBsTM. CONCLUSION: KL-BoBsTM is
      potentially very useful as a first line test for aneusomy detection because of
      its lower cost, rapid detection, and ability to generate a molecular karyotype
      for samples that fail to grow in culture.

PMID- 23138850
TI  - miR-196a overexpression and miR-196a2 gene polymorphism are prognostic predictors
      of oral carcinomas.
AB  - BACKGROUND: Oral squamous cell carcinoma (OSCC) is prevalent worldwide, and
      survival in OSCC has not improved significantly in the last few decades.
      MicroRNAs have an important regulatory role in oral carcinogenesis. This study
      investigated the prognostic implications of miR-196 expression and the rs11614913
      genotype of the miR-196a2 gene in OSCC. METHODS: The clinicopathologic
      implications of miR-196 in OSCC were investigated using expression assays and
      genotyping, and the functional role of miR-196 in OSCC pathogenesis was
      investigated using exogenous expression and knockdown. RESULTS: miR-196 was up
      regulated in OSCC tissue relative to control mucosa. High expression of miR-196a,
      but not miR-196b, was associated with tumor recurrence, nodal metastasis, and
      mortality. Plasma miR-196a levels could be used to distinguish patients from
      controls with a separating power of 0.75. Multivariate analysis showed that both
      high miR-196a expression and TT genotype were independent predictors for poor
      survival in OSCC. The risk of mortality was greatest for patients with high miR
      196a level and positive node status. Expression of miR-196 enhanced oncogenesis
      of OSCC cells, while inhibition of miR-196 expression attenuated such effects.
      CONCLUSIONS: High miR-196a expression in tumor tissue and the presence of the TT
      variant of miR-196a2 gene indicate worse survival in OSCC.

PMID- 23138849
TI  - Co-transcriptional nuclear actin dynamics.
AB  - Actin is a key player for nuclear structure and function regulating both
      chromosome organization and gene activity. In the cell nucleus actin interacts
      with many different proteins. Among these proteins several studies have
      identified classical nuclear factors involved in chromatin structure and
      function, transcription and RNA processing as well as proteins that are normally
      involved in controlling the actin cytoskeleton. These discoveries have raised the
      possibility that nuclear actin performs its multi task activities through tight
      interactions with different sets of proteins. This high degree of promiscuity in
      the spectrum of protein-to-protein interactions correlates well with the
      conformational plasticity of actin and the ability to undergo regulated changes
      in its polymerization states. Several of the factors involved in controlling head
      to-tail actin polymerization have been shown to be in the nucleus where they seem
      to regulate gene activity. By focusing on the multiple tasks performed by actin
      and actin-binding proteins, possible models of how actin dynamics controls the
      different phases of the RNA polymerase II transcription cycle are being
      identified.

PMID- 23138851
TI  - Loss of OPA1 disturbs cellular calcium homeostasis and sensitizes for
      excitotoxicity.
AB  - Optic atrophy 1 (OPA1) mutations cause dominant optic atrophy (DOA) with retinal
      ganglion cell (RGC) and optic nerve degeneration. The mechanism for the selective
      degeneration of RGCs in DOA remains elusive. To address the mechanism, we reduced
      OPA1 protein expression in cell lines and RGCs by RNA interference. OPA1 loss
      results in mitochondrial fragmentation, deficiency in oxidative phosphorylation,
      decreased ATP levels, decreased mitochondrial Ca(2+) retention capacity, reduced
      mtDNA copy numbers, and sensitization to apoptotic insults. We demonstrate
      profound cristae depletion and loss of crista junctions in OPA1 knockdown cells,
      whereas the remaining crista junctions preserve their normal size. OPA1-depleted
      cells exhibit decreased agonist-evoked mitochondrial Ca(2+) transients and
      corresponding reduction of NAD(+) to NADH, but the impairment in NADH oxidation
      leads to an overall more reduced mitochondrial NADH pool. Although in our model
      OPA1 loss in RGCs has no apparent impact on mitochondrial morphology, it
      decreases buffering of cytosolic Ca(2+) and sensitizes RGCs to excitotoxic
      injury. Exposure to glutamate triggers delayed calcium deregulation (DCD), often
      in a reversible manner, indicating partial resistance of RGCs to this injury.
      However, when OPA1 is depleted, DCD becomes irreversible. Thus, our data show
      that whereas OPA1 is required for mitochondrial fusion, maintenance of crista
      morphology and oxidative phosphorylation, loss of OPA1 also results in defective
      Ca(2+) homeostasis.

PMID- 23138853
TI  - Examining network dynamics after traumatic brain injury using the extended
      unified SEM approach.
AB  - The current study uses effective connectivity modeling to examine how individuals
      with traumatic brain injury (TBI) learn a new task. We make use of recent
      advancements in connectivity modeling (extended unified structural equation
      modeling, euSEM) and a novel iterative grouping procedure (Group Iterative
      Multiple Model Estimation, GIMME) in order to examine network flexibility after
      injury. The study enrolled 12 individuals sustaining moderate and severe TBI to
      examine the influence of task practice on connections between 8 network nodes
      (bilateral prefrontal cortex, anterior cingulate, inferior parietal lobule, and
      Crus I in the cerebellum). The data demonstrate alterations in networks from pre
      to post practice and differences in the models based upon distinct learning
      trajectories observed within the TBI sample. For example, better learning in the
      TBI sample was associated with diminished connectivity within frontal systems and
      increased frontal to parietal connectivity. These findings reveal the potential
      for using connectivity modeling and the euSEM to examine dynamic networks during
      task engagement and may ultimately be informative regarding when networks are
      moving in and out of periods of neural efficiency. 

PMID- 23138852
TI  - Clinically-translated silica nanoparticles as dual-modality cancer-targeted
      probes for image-guided surgery and interventions.
AB  - Early diagnosis and treatment of melanoma are essential to minimizing morbidity
      and mortality. The presence of lymph node metastases is a vital prognostic
      predictor, and accurate identification by imaging has important implications for
      disease staging, prognosis, and clinical outcome. Sentinel lymph node (SLN)
      mapping procedures are limited by a lack of intraoperative visualization tools
      that can aid accurate determination of disease spread and delineate nodes from
      adjacent critical neural and vascular structures. Newer methods for circumventing
      these issues can exploit a variety of imaging tools, including biocompatible
      particle-based platforms coupled with portable device technologies for use with
      image-guided surgical and interventional procedures. We describe herein a
      clinically-translated, integrin-targeting platform for use with both PET and
      optical imaging that meets a number of key design criteria for improving SLN
      tissue localization and retention, target-to-background ratios, and clearance
      from the site of injection and the body. The use of such agents for selectively
      probing critical cancer targets may elucidate important insights into cellular
      and molecular processes that govern metastatic disease spread. Coupled with
      portable, real-time optical camera systems, we show that pre-operative PET
      imaging findings for mapping metastatic disease in clinically-relevant larger
      animal models can be readily translated into the intraoperative setting for
      direct visualization of the draining tumor lymphatics and fluorescent SLN/s with
      histologic correlation. The specificity of this platform, relative to the
      standard-of-care radiotracer, (18)F-FDG, for potentially discriminating
      metastatic disease from inflammatory processes is also discussed in the setting
      of surgically-based or interventionally-driven therapies.

PMID- 23138854
TI  - "In situ" hard mask materials: a new methodology for creation of vertical silicon
      nanopillar and nanowire arrays.
AB  - A novel, simple and in situ hard mask technology that can be used to develop high
      aspect ratio silicon nanopillar and nanowire features on a substrate surface is
      demonstrated. The technique combines a block copolymer inclusion method that
      generates nanodot arrays on substrate and an inductively coupled plasma (ICP)
      etch processing step to fabricate Si nanopillar and nanowire arrays. Iron oxide
      was found to be an excellent resistant mask over silicon under the selected
      etching conditions. Features of a very high aspect ratio can be created by this
      method. The nanopillars have uniform diameter and smooth sidewalls throughout
      their entire length. The diameter (15-27 nm) and length of the nanopillars can be
      tuned easily. Different spectroscopic and microscopic techniques were used to
      examine the morphology and size, surface composition and crystallinity of the
      resultant patterns. The methodology developed may have important technological
      applications and provide an inexpensive manufacturing route to nanodimensioned
      topographical patterns. The high aspect ratio of the features may have importance
      in the area of photonics and the photoluminescence properties are found to be
      similar to those of surface-oxidized silicon nanocrystals and porous silicon.

PMID- 23138856
TI  - Solid-state NMR sequential assignments of the C-terminal oligomerization domain
      of human C4b-binding protein.
AB  - The complement 4 binding protein (C4bp) plays a crucial role in the inhibition of
      the complement cascade. It has an extraordinary seven-arm octopus-like structure
      with 7 tentacle-like identical chains, held together at their C-terminal end. The
      C-terminal domain does oligomerize in isolation, and is necessary and sufficient
      to oligomerize full-length C4bp. It is predicted to form a seven-helix coiled
      coil, and its multimerization properties make it a promising vaccine adjuvant,
      probably by enhancing the structural stability and binding affinity of the
      presented antigen. Here, we present the solid-state NMR resonance assignment of
      the human C4bp C-terminal oligomerization Domain, hC4pbOD, and the corresponding
      secondary chemical shifts. 

PMID- 23138855
TI  - Is there an added value of cardiopulmonary exercise testing in sarcoidosis
      patients?
AB  - BACKGROUND: Cardiopulmonary exercise testing (CPET) with blood gas analysis may
      be helpful when there is a discrepancy between clinical findings and physiologic
      tests at rest. The aim of this study was to examine the added value of CPET
      compared to the measurement of the diffusing capacity of the lung for carbon
      monoxide (DLCO) in detecting impaired pulmonary gas exchange in sarcoidosis
      patients. METHODS: The clinical records of 160 (age = 41.3 +/- 10.0 years; number
      of females = 63) sarcoidosis patients referred to the former MUMC ild care center
      were retrospectively reviewed. Patients performed a symptom-limited incremental
      exercise test with blood gas analysis on a bicycle ergometer. DLCO was measured
      by the single-breath method. RESULTS: DLCO (mean = 83.2 +/- 18.0 %) below 80 % of
      predicted was demonstrated by 38 % of the sarcoidosis patients in our sample. Of
      the patients with normal DLCO (n = 99, 61.9 %), the P(A-a)O(2) at maximal
      exercise [P(A-a)O(2)max] was moderately increased (>2.5 kPa) in 69.7 % and
      excessively increased (>4.7 kPa) in 18.2 %. Pulmonary gas exchange impairment
      (PGEI) was more obvious in patients with lower DLCO values. A DLCO value below 60
      % of predicted indicated substantial gas exchange impairment. PaO(2) at rest,
      DLCO, and FVC as a percentage of predicted and radiographic staging predicted 40
      % of the PGEI at maximal exercise. CONCLUSION: A substantial number of the
      symptomatic sarcoidosis patients with normal DLCO appeared to have PGEI at
      maximal exercise, suggesting that normal DLCO at rest is an inappropriate
      predictor of abnormal pulmonary gas exchange during exercise. CPET appeared to
      offer added value in detecting impaired gas exchange during exercise in
      sarcoidosis patients with unexplained disabling symptoms.

PMID- 23138857
TI  - Backbone and sterospecific methyl side chain resonance assignments of the
      homodimeric zinc sensor AdcR (32 kDa) in the apo- and Zn(II)-bound states.
AB  - Streptococcus pneumoniae adhesin competence repressor (AdcR) is a Zn(II)
      dependent 32 kDa homodimer that controls the transcription of a zinc-specific ABC
      uptake system (AdcABC), three pneumococcal histidine triad proteins (PhtA, PhtD
      and PhtE), and an AdcA homolog AdcAII. AdcR is the first metal-dependent member
      of the MarR family of prokaryotic transcriptional repressors. Two-dimensional NMR
      studies reveal large changes in the spectrum upon Zn(II) binding. Near complete
      backbone and stereospecific methyl group resonance assignments for apo- and
      Zn(II)-AdcR are presented here. 

PMID- 23138858
TI  - 1H, 13C, and 15N backbone and side chain resonance assignments of thermophilic
      Geobacillus kaustophilus cyclophilin-A.
AB  - Cyclophilins catalyze the reversible peptidyl-prolyl isomerization of their
      substrates and are present across all kingdoms of life from humans to bacteria.
      Although numerous biological roles have now been discovered for cyclophilins,
      their function was initially ascribed to their chaperone-like activity in protein
      folding where they catalyze the often rate-limiting step of proline
      isomerization. This chaperone-like activity may be especially important under
      extreme conditions where cyclophilins are often over expressed, such as in tumors
      for human cyclophilins (Lee Archiv Pharm Res 33(2): 181-187, 2010), but also in
      organisms that thrive under extreme conditions, such as theromophilic bacteria.
      Moreover, the reversible nature of the peptidyl-prolyl isomerization reaction
      catalyzed by cyclophilins has allowed these enzymes to serve as model systems for
      probing the role of conformational changes during catalytic turnover (Eisenmesser
      et al. Science 295(5559): 1520-1523, 2002; Eisenmesser et al. Nature 438(7064):
      117-121, 2005). Thus, we present here the resonance assignments of a thermophilic
      cyclophilin from Geobacillus kaustophilus derived from deep-sea sediment (Takami
      et al. Extremophiles 8(5): 351-356, 2004). This thermophilic cyclophilin may now
      be studied at a variety of temperatures to provide insight into the comparative
      structure, dynamics, and catalytic mechanism of cyclophilins. 

PMID- 23138859
TI  - Randomized clinical trial comparing lightweight mesh with heavyweight mesh for
      primary inguinal hernia repair.
AB  - PURPOSE: The aim of the present randomized clinical trial was to compare feeling
      of a foreign body and the early and late outcomes after inguinal hernia repair
      with the heavyweight (HW) mesh and lightweight (LW) mesh during a 12-month follow
      up at a single specialist center. MATERIALS AND METHODS: One hundred and ten
      patients were randomized into HW and LW mesh groups, both of which underwent
      unilateral primary inguinal hernia via the Lichtenstein technique. At each
      postoperative visit, any complication, recurrence, feeling of a foreign body,
      quality of life, residual pain, and numbness were recorded. RESULTS: Complaint of
      feeling of a foreign body on the repaired side was more frequent in the HW mesh
      group than in the LW mesh group (P < 0.05). Fewer patients in the LW mesh group
      reported postoperative numbness around the groin or down the thigh than did those
      in the HW mesh group (P < 0.05). At 12-month follow-up, however, there was no
      difference between the LW and HW mesh groups as regards the incidence or severity
      of pain or discomfort and recurrence rate and nor was there any significant
      dissimilarity between the two study groups in any dimension of quality of life on
      the SF-36. CONCLUSION: There was no significant difference between our LW mesh
      and HW mesh groups in terms of chronic pain incidence, recurrence rate, and
      quality of life following inguinal hernia repair. However, fewer patients in the
      LW mesh group reported numbness around the groin or down the thigh postsurgery
      than did those in the HW mesh group and therein may lie in the superiority of LW
      mesh for inguinal hernia repair. Larger cohort studies with longer follow-up
      periods are required to elucidate in the future the benefits of the LW mesh.

PMID- 23138860
TI  - Open inguinal hernia repair with the use of polyglycolic acid/trimethylene
      carbonate absorbable mesh: a critical update of the long-term results.
AB  - PURPOSE: Our group evaluated on a pilot basis open inguinal hernia repair with
      the use of a fully absorbable mesh aiming to take mesh inguinal hernia repair one
      step forward. The purpose of the present study was to assess the long-term
      results of the proposed technique. METHODS: Patients that were included in our
      previous report were followed up at 3 years after the initial operation. RESULTS:
      Ten patients underwent open inguinal hernia repair with the use of an absorbable
      polyglycolic acid/trimethylene carbonate mesh. 3 years after the procedure, from
      the total of ten patients, two were lost to follow-up (20 %). Three patients
      (37.5 %), one with direct and two with indirect hernia, were diagnosed clinically
      with a recurrence at the follow-up of 3 years. Recurrences were developed nearly
      2 years--median 24 months (range 18-30)--after the initial operation. Among
      patients without recurrence none complained about chronic pain, foreign body
      sensation or numbness. On the other hand, chronic pain was a constant complain in
      the recurrence patient group. CONCLUSIONS: The results of the 3-year follow-up in
      the given patient sample alleviate the initial enthusiasm regarding the use of an
      absorbable mesh for inguinal hernia repair as an attractive alternative and
      causes skepticism about the generalized use of the procedure in its certain form.

PMID- 23138862
TI  - Engineering the binding site of an antibody against N-glycolyl GM3: from
      functional mapping to novel anti-ganglioside specificities.
AB  - The structurally related gangliosides N-glycolyl GM3 and N-acetyl GM3 are
      potential targets for tumor immunotherapy. 14F7 is a monoclonal antibody able to
      discriminate the tumor-specific antigen N-glycolyl GM3 from the closely related N
      acetyl GM3 on the basis of the presence of a single additional hydroxyl group in
      the former. A combinatorial phage display strategy, based on the screening of a
      large library followed by refined mutagenesis, allowed a thorough exploration of
      the binding chemistry of this unique antibody. Three essential features of the
      heavy chain variable region were identified: two aromatic rings (in positions 33
      and 100D) contributing to the binding site architecture and an arginine residue
      (position 98) critical for recognition. Directed evolution of 14F7 resulted in
      novel variants that cross-react with the tumor-associated antigen N-acetyl GM3
      and display recurrent replacements: the substitution W33Q and the appearance of
      additional arginine residues at several positions of CDR H1. Successful
      conversion of such engineered variable regions into whole cross-reactive anti-GM3
      immunoglobulins validated our phage-based approach to study and modify the lead
      antibody 14F7. The resulting family of closely related antibodies offers new
      tools to study the mechanisms of cell death induced by antibodies targeting
      gangliosides. In vitro directed evolution was useful to overcome the technical
      limitations to obtain anti-ganglioside antibodies. The case of 14F7 illustrates
      the power of combining library screening with focused site-directed randomization
      for a comprehensive scanning of protein interactions.

PMID- 23138861
TI  - A meta-analysis comparing tacker mesh fixation with suture mesh fixation in
      laparoscopic incisional and ventral hernia repair.
AB  - OBJECTIVE: To systematically compare the tacker mesh fixation (TMF) with the
      suture mesh fixation (SMF) in laparoscopic incisional and ventral hernia (LIVH)
      repair. METHODS: Trials evaluating the TMF with the SMF in LIVH repair were
      analysed using the statistical tool RevMan((r)). Combined dichotomous and
      continuous data were expressed as odds ratio (OR) and mean difference (MD),
      respectively. RESULTS: Four trials (2 randomised and 2 non-randomised)
      encompassing 207 patients undergoing LIVH repair with TMF versus SMF were
      retrieved from the standard electronic databases and analysed systematically.
      Ninety-nine patients underwent TMF and 108 patients underwent SMF in LIVH repair.
      There was no statistically significant heterogeneity (p = 0.27)] among trials. In
      the fixed-effects model, LIVH repair with TMF was associated with shorter
      operation time (MD, -23.65; 95 % CI, -31.06, -16.25; z = 6.26; p < 0.00001). Four
      to six-week postoperative pain score was significantly lower (MD, -0.69; 95 %
      CI, -1.16, -0.23; z = 2.92; p < 0.004) following TMF. Peri-operative
      complications (p = 0.65), length of hospital stay (p = 1) and risk of hernia
      recurrence (OR, 1.54; 95 % CI, 0.38, 6.27; z = 0.61; p = 0.54) following TMF and
      SMF were statistically not different. CONCLUSION: TMF in LIVH repair is
      associated with shorter operative time and lesser postoperative pain. TMF is
      comparable with SMF in terms of peri-operative complications, length of hospital
      stay and hernia recurrence. Therefore, TMF may be used in LIVH repair. However,
      further randomised trials recruiting higher number of patients are required to
      validate these findings.

PMID- 23138865
TI  - [Hyperbaric oxygen therapy for necrotizing soft tissue infections: contra].
AB  - INTRODUCTION: Hyperbaric oxygen therapy (HBOT) is discussed as an adjuvant option
      to treat necrotizing soft tissue infections (NSTI). While the Federal Joint
      Committee decided in 2007 not to support HBOT for the indication necrotizing
      fasciitis and Fournier's gangrene, it was decided to accept HBOT for treatment of
      clostridial myonecrosis for the German health insurance. Thus, in Germany
      necrotizing fasciitis (NF) is not a confirmed indication for HBOT. Against this
      background the cons of the clinical benefits of HBOT should be formulated.
      METHODS: A literature search (MEDLINE/EMBASE/COCHRANE/manual search) using the
      keywords "necrotizing fasciitis", "Fournier's gangrene", "necrotizing
      cellulitis", "necrotizing soft tissue infections" as well as "hyperbaric
      medicine", "hyperbaric therapy" and "hyperbaric treatment" was carried out. An
      analysis of the spatial distribution of German hyperbaric oxygen chambers
      enabling intensive care (HOC-IC) was made. RESULTS: A total of 250 articles with
      n=2,556 NSTI patients (n=993 treated by HBOT) was found and 50% of the articles
      were case reports or series. There were only ten retrospective studies comparing
      the effects of HBOT with non-HBO treatment and none of them verified the benefit
      of HBOT in NF patients. In Germany only nine hyperbaric oxygen chambers (HOC-IC)
      enable intensive care. Currently, patient data are not included in scientific
      studies or multicenter studies, while studies assessing the benefit with higher
      evidence levels have been required for more than 15 years. CONCLUSIONS: The
      previously published human clinical studies do not confirm any therapeutic
      benefit of HBOT in NF patients. Any time delay in the start of surgical therapy
      by HBOT would not be acceptable. In Germany a comprehensive clinical care with
      HOC is not possible. On average the additional costs of HBO treatment for NF
      patients is approximately 8,000-25,000 <euro>/patient which is not generally
      reimbursed by health insurance companies. Initializing a register study to assess
      the benefit of HBOT in NF patients appears feasible and is urgently needed.

PMID- 23138864
TI  - [Clinical symptoms and therapy of necrotizing skin and soft tissue infections].
AB  - Skin and soft tissue infections are among the most common diseases requiring
      surgical treatment. The presentation of patients varies from folliculitis to
      severe necrotizing infections with a fatal outcome. The diagnosis of a
      necrotizing infection is often difficult. The correct diagnosis is often made
      after deterioration of the patient's condition in the rapid course of the
      disease. The early and correct diagnosis and immediate surgery are decisive for
      the prognosis. Treatment at a specialized intensive care unit and the
      administration of a broad spectrum antibiotic are pivotal for the survival of
      individual patients.

PMID- 23138867
TI  - Advanced nanoparticle generation and excitation by lasers in liquids.
AB  - Today, nanoparticles are widely implemented as functional elements onto surfaces,
      into volumes and as nano-hybrids, resulting for example in bioactive composites
      and biomolecule conjugates. However, only limited varieties of materials
      compatible for integration into advanced functional materials are available:
      nanoparticles synthesized using conventional gas phase processes are often
      agglomerated into micro powders that are hard to re-disperse into functional
      matrices. Chemical synthesis methods often lead to impurities of the nanoparticle
      colloids caused by additives and precursor reaction products. In the last decade,
      laser ablation and nanoparticle generation in liquids has proven to be a unique
      and efficient technique to generate, excite, fragment, and conjugate a large
      variety of nanostructures in a scalable and clean manner. This editorial briefly
      highlights selected recent advancements and critical aspects in the field of
      pulsed laser-based nanoparticle generation and manipulation, including exemplary
      strategies to harvest the unique properties of the laser-generated nanomaterials
      in the field of biomedicine and catalysis. The presented critical aspects address
      future assignments such as size control and scale-up.

PMID- 23138868
TI  - How is functional specificity achieved through disordered regions of proteins?
AB  - N-type inactivation of potassium channels is controlled by cytosolic loops that
      are intrinsically disordered. Recent experiments have shown that the mechanism of
      N-type inactivation through disordered regions can be stereospecific and vary
      depending on the channel type. Variations in mechanism occur despite shared
      coarse grain features such as the length and amino acid compositions of the
      cytosolic disordered regions. We have adapted a phenomenological model designed
      to explain how specificity in molecular recognition is achieved through
      disordered regions. We propose that the channel-specific observations for N-type
      inactivation represent distinct mechanistic choices for achieving function
      through conformational selection versus induced fit. It follows that the dominant
      mechanism for binding and specificity can be modulated through subtle changes in
      the amino acid sequences of disordered regions, which is interesting given that
      specificity in function is realized in the absence of autonomous folding.

PMID- 23138869
TI  - Evidence for a strong trans influence of the diboran(4)yl ligand.
AB  - Diboran(4)yl Pt(II) complexes: Selective oxidative addition of one B-I bond in
      B(2)(NMe(2))(2)I(2) to [Pt(PiPr(3))(2)] affords a trans-diboran(4)yl platinum(II)
      complex (see scheme; Ar(F) = 3,5-(CF(3))(2)C(6)H(3)). Comparison of its Pt-I bond
      lengths and the Pt-Br bond lengths of its bromine analogue with related species
      served to evaluate the trans influence of the ligand. The trans influence enabled
      facile halide abstraction to generate T-shaped 14-electron diboran(4)yl
      platinum(II) complexes.

PMID- 23138871
TI  - Targeting microRNAs to modulate TRAIL-induced apoptosis of cancer cells.
AB  - MicroRNAs (miRNAs) are endogenously expressed small non-coding RNAs, which are
      evolutionarily conserved and function as regulators of gene expression. These
      molecules are involved in numerous biological processes including
      differentiation, development, proliferation and apoptosis. Further investigation
      identifies that miRNAs may act as either potent oncogenes or tumor-suppressor
      genes, linking to cancer initiation and progression. Tumor necrosis factor (TNF)
      related apoptosis-inducing ligand (TRAIL), as a member of the TNF family, is an
      attractive therapeutic target in cancer because it directly induces tumor cell
      apoptosis and has no cytotoxicity to normal cell types in vitro or in vivo.
      However, the resistance to TRAIL-induced apoptosis limits its clinical
      effectiveness. Interestingly, several studies convincingly demonstrate a role of
      miRNAs in modulating sensitive/resistant phenotypes to TRAIL. Here, we review the
      current findings about miRNAs involved in TRAIL-induced apoptosis in different
      cancers.

PMID- 23138870
TI  - Combination of vinblastine and oncolytic herpes simplex virus vector expressing
      IL-12 therapy increases antitumor and antiangiogenic effects in prostate cancer
      models.
AB  - Oncolytic herpes simplex virus (oHSV)-1-based vectors selectively replicate in
      tumor cells causing direct killing, that is, oncolysis, while sparing normal
      cells. The oHSVs are promising anticancer agents, but their efficacy, when used
      as single agents, leaves room for improvement. We hypothesized that combining the
      direct oncolytic and antiangiogenic activities of the interleukin (IL)-12
      secreting NV1042 oHSV with microtubule disrupting agents (MDAs) would be an
      effective means to enhance antitumor efficacy. Vinblastine (VB) was identified
      among several MDAs screened, which displayed consistent and potent cytotoxic
      killing of both prostate cancer and endothelial cell lines. In matrigel tube
      forming assays, VB was found to be highly effective at inhibiting tube formation
      of human umbilical vein endothelial cells. The combination of VB with NV1023 (the
      parental virus lacking IL-12) or NV1042 showed additive or synergistic activity
      against prostate cancer cell lines, and was not due to increased oHSV replication
      by VB. In athymic mice bearing CWR22 prostate tumors, VB in combination with
      NV1042 was superior to the combination of VB plus NV1023 in reducing tumor
      burden, appeared to be nontoxic and resulted in a statistically significant
      diminution in the number of CD31(+) cells as compared with other treatment
      groups. In human organotypic cultures using surgical samples from radical
      prostatectomies, both NV1023 and NV1042 were localized specifically to the
      epithelial cells of prostatic glands but not to the surrounding stroma. These
      data highlight the therapeutic advantage of combining the dual-acting antitumor
      and antiangiogenic activities of oHSVs and MDAs.

PMID- 23138872
TI  - Serum-free freezing media support high cell quality and excellent ELISPOT assay
      performance across a wide variety of different assay protocols.
AB  - Robust and sensitive ELISPOT protocols are commonly applied concomitant with the
      development of new immunotherapeutics. Despite the knowledge that individual
      serum batches differ in their composition and may change properties over time,
      serum is still commonly used in immunologic assays. Commercially available serum
      batches are expensive, limited in quantity and need to be pretested for
      suitability in immunologic assays, which is a laborious process. The aim of this
      study was to test whether serum-free freezing media can lead to high cell
      viability and favorable performance across multiple ELISPOT assay protocols.
      Thirty-one laboratories from ten countries participated in a proficiency panel
      organized by the Cancer Immunotherapy Immunoguiding Program to test the influence
      of different freezing media on cell quality and immunologic function. Each center
      received peripheral blood mononuclear cells which were frozen in three different
      media. The participants were asked to quantify antigen-specific CD8+ T-cell
      responses against model antigens using their locally established IFN-gamma
      ELISPOT protocols. Self-made and commercially available serum-free freezing media
      led to higher cell viability and similar cell recovery after thawing and resting
      compared to freezing media supplemented with human serum. Furthermore, the test
      performance as determined by (1) background spot production, (2) replicate
      variation, (3) frequency of detected antigen-specific spots and (4) response
      detection rate was similar for serum and serum-free conditions. We conclude that
      defined and accessible serum-free freezing media should be recommended for
      freezing cells stored for subsequent ELISPOT analysis.

PMID- 23138873
TI  - Immunomodulatory activity of SGI-110, a 5-aza-2'-deoxycytidine-containing
      demethylating dinucleotide.
AB  - PURPOSE: Pharmacologic DNA hypomethylation holds strong promises in cancer
      immunotherapy due to its immunomodulatory activity on neoplastic cells. Searching
      for more efficient DNA hypomethylating agents to be utilized to design novel
      immunotherapeutic strategies in cancer, we investigated the immunomodulatory
      properties of the new DNA hypomethylating agent SGI-110, that is resistant to in
      vivo inactivation by cytidine deaminase. EXPERIMENTAL DESIGN: Cutaneous melanoma,
      mesothelioma, renal cell carcinoma, and sarcoma cells were treated in vitro with
      SGI-110. RT-PCR, quantitative RT-PCR, quantitative methylation-specific PCR, and
      flow cytometric analyses were performed to investigate changes induced by SGI-110
      in the constitutive immune profile of cancer cells. The recognition by gp100
      specific CTL of gp100-positive melanoma cells, treated or not with SGI-110, was
      tested by LDH release assays. RESULTS: SGI-110 induced/up-regulated the
      expression of investigated cancer/testis antigens (CTA) (i.e., MAGE-A1, MAGE-A2,
      MAGE-A3, MAGE-A4, MAGE-A10, GAGE 1-2, GAGE 1-6, NY-ESO-1, and SSX 1-5) in all
      cancer cell lines studied, both at mRNA and at protein levels. Quantitative
      methylation-specific PCR analyses identified a hypomethylation of MAGE-A1 and NY
      ESO-1 promoters in SGI-110-treated neoplastic cells, demonstrating a direct role
      of pharmacologic DNA demethylation in CTA induction. SGI-110 also up-regulated
      the expression of HLA class I antigens and of ICAM-1, resulting in an improved
      recognition of cancer cells by gp100-specific CTL. CONCLUSIONS: Our findings show
      that SGI-110 is a highly attractive therapeutic agent to comprehensively increase
      immunogenicity and immune recognition of neoplastic cells, and provide the
      scientific rationale for its clinical development to design novel chemo
      immunotherapeutic approaches in cancer patients.

PMID- 23138874
TI  - The effect of protein A cycle number on the performance and lifetime of an anion
      exchange polishing step.
AB  - Most mAb platform purification processes consist of an affinity capture step
      followed by one or two polishing steps. An understanding of the performance
      linkages between the unit operations can lead to robust manufacturing processes.
      In this study, a weak-partitioning anion-exchange chromatography polishing step
      used in a mAb purification process was characterized through high-throughput
      screening (HTS) experiments, small-scale experiments including a cycling study
      performed on qualified scale-down models, and large-scale manufacturing runs.
      When material from a Protein A column that had been cycled <10* was loaded on the
      AEX resin, early breakthrough of impurities and premature loss of capacity was
      observed. As the cycle number on the Protein A resin increased, the capacity of
      the subsequent AEX step increased. Different control strategies were considered
      for preventing impurity breakthrough and improving AEX resin lifetimes. Depth
      filtration of the Protein A peak pool significantly improved the AEX resin
      capacity, robustness, and lifetime. Further, the turbidity of the Protein A pool
      has the potential for use as an in-process control parameter for monitoring the
      performance of the AEX step.

PMID- 23138875
TI  - Quercetin and quercitrin protect against cytokine-induced injuries in RINm5F beta
      cells via the mitochondrial pathway and NF-kappaB signaling.
AB  - Quercetin, existing mostly in its glycoside form quercitrin, is the most widely
      distributed flavonoid in nature. It possesses various potential effects as an
      antioxidant, anti-inflammatory for cell damage of beta-cells, however, studies on
      this topic are limited and controversial. In order to examine the effects of
      quercetin on type I diabetes mellitus, we investigated the role of
      quercetin/quercitrin in cytokine-induced beta-cell injuries in RINm5F rat
      insulinoma cells. Cell viability, glucose-stimulated insulin secretion (GSIS),
      intracellular reactive oxygen species (ROS), nitric oxide (NO) and inflammation
      or apoptosis-associated protein expression were measured with or without
      quercetin/quercitrin treatment. We also compared the differences between the
      aglycone and the glycoside forms of quercetin, with the aim to shed some light on
      their structures and transportation into cells. The results showed that
      quercetin/quercitrin protected against cytokine-induced cell death, improved
      GSIS, and inhibited ROS as well as NO accumulation. These effects were associated
      with reduced expression of inducible nitric oxide synthases (iNOS) and inhibited
      translocation of nuclear factor-kappaB (NF-kappaB). Also, quercetin/quercitrin
      suppressed cytochrome c release from mitochondria and the following alteration of
      downstream proteins, suggesting that mitochondrial apoptosis was attenuated by
      quercetin treatment. In summary, quercetin and quercitrin are potential
      candidates to prevent beta-cell death via the mitochondrial pathway and NF-kappaB
      signaling, and quercetin may be more efficacious than quercitrin as an anti
      diabetic agent.

PMID- 23138876
TI  - Thermal grill-evoked sensations of heat correlate with cold pain threshold and
      are enhanced by menthol and cinnamaldehyde.
AB  - BACKGROUND: Thunberg's thermal grill produces a sensation of strong heat upon
      skin contact with spatially interlaced innocuous warm and cool stimuli. METHODS:
      To examine the classes of peripheral axons that might contribute to this
      illusion, the effects of topical l-menthol, an activator of TRPM8, and
      cinnamaldehyde, a TRPA1 agonist, on the magnitude of thermal sensations were
      examined during grill stimulation in healthy volunteers. RESULTS: Under control
      conditions, cutaneous grill stimulation (interlaced 20/40  degrees C) evoked a
      sensation of heat, and for individual subjects, the magnitude of this heat
      sensation was positively correlated with cold pain threshold (CPT). Menthol
      increased the CPT and enhanced the magnitude of grill-evoked heat. Cinnamaldehyde
      intensified warm sensations, reduced heat pain threshold and also enhanced grill
      evoked heat. CONCLUSIONS: Both TRPM8-expressing and TRPA1-expressing afferent
      axons can affect grill-evoked thermal sensations. The enhancement of grill-evoked
      sensations of temperature with menthol and cinnamaldehyde may provide an
      additional clinically relevant means of testing altered thermal sensitivity,
      which is often affected in neuropathic patient groups.

PMID- 23138877
TI  - Cost analysis of enhancing linkages to HIV care following jail: a cost-effective
      intervention.
AB  - We are not aware of published cost-effectiveness studies addressing community
      transitional programs for HIV-infected jail detainees. To address this gap, data
      from 9 sites of EnhanceLink, a project that enrolled HIV-infected releasees from
      jails across the US, were examined. Figures on the number of clients served, cost
      of linkage services, number of linkages and 6-month sustained linkages to
      community HIV care, and number of clients achieving viral suppression were
      assessed for subjects released in the first quarter of 2010 (n = 543). The cost
      analysis included all costs that participating service agencies incurred. A cost
      effectiveness analysis was conducted to estimate the new HIV cases averted by
      EnhanceLink and the cost per quality-adjusted life year saved by the program. The
      mean cost per linked client was $4,219; the mean cost per 6-month sustained
      linkage was $4,670; and the mean cost per client achieving viral suppression was
      $8,432. Compared to standard care, the cost per additional quality-adjusted life
      year saved was $72,285, suggesting that the EnhanceLink interventions were cost
      effective from the societal perspective.

PMID- 23138878
TI  - A novel colorimetric and fluorescent "off-on" chemosensor for Cu2+ based on a
      rhodamine derivative bearing naphthyridine group.
AB  - A new rhodamine-based derivative bearing a naphthyridine group (compound 1) was
      synthesized as a colorimetric and fluorescent "off-on" chemosensor for Cu(2+) in
      aqueous solutions. The sensing behaviors of 1 toward various metal ions in
      neutral aqueous solutions were investigated by absorption and fluorescence
      spectroscopies. Compound 1 is found to exhibit a significant increase in
      absorbance at 561 nm and an amplified fluorescence at 590 nm toward Cu(2+) in a
      selective, sensitive and rapid manner. The quantification of Cu(2+) by 1 using an
      absorption spectroscopy method was satisfactory in the linear working range 0.9
      10 MUM, with a detection limit of 5.4 * 10(-8) M for Cu(2+) and good tolerance of
      other metal ions. Upon addition of Cu(2+), the spirolactam ring (colorless and
      nonfluorescent) of 1 was opened to ring-opened amide (red color and fluorescent)
      and a 1:1 stoichiochemetry for the 1-Cu(2+) complex was formed with an
      association constant of 1.57 * 10(4) M(-1).

PMID- 23138880
TI  - Impact commentaries. Unusual type of benign X linked muscular dystrophy.

PMID- 23138879
TI  - Responsive culture platform to examine the influence of microenvironmental
      geometry on cell function in 3D.
AB  - We describe the development of a well-based cell culture platform that enables
      experimenters to control the geometry and connectivity of cellular
      microenvironments spatiotemporally. The base material is a hydrogel comprised of
      photolabile and enzyme-labile crosslinks and pendant cell adhesion sequences,
      enabling spatially-specific, in situ patterning with light and cell-dictated
      microenvironment remodeling through enzyme secretion. Arrays of culture wells of
      varying shape and size were patterned into the hydrogel surface using
      photolithography, where well depth was correlated with irradiation dose. The
      geometry of these devices can be subsequently modified through sequential
      patterning, while simultaneously monitoring changes in cell geometry and
      connectivity. Towards establishing the utility of these devices for dynamic
      evaluation of the influence of physical cues on tissue morphogenesis, the effect
      of well shape on lung epithelial cell differentiation (i.e., primary mouse
      alveolar type II cells, ATII cells) was assessed. Shapes inspired by alveoli were
      degraded into hydrogel surfaces. ATII cells were seeded within the well-based
      arrays and encapsulated by the addition of a top hydrogel layer. Cell
      differentiation in response to these geometries was characterized over 7 days of
      culture with immunocytochemistry (surfactant protein C, ATII; T1alpha protein,
      alveolar type I (ATI) differentiated epithelial cells) and confocal image
      analysis. Individual cell clusters were further connected by eroding channels
      between wells during culture via controlled two-photon irradiation. Collectively,
      these studies demonstrate the development and utility of responsive hydrogel
      culture devices to study how a range of microenvironment geometries of evolving
      shape and connectivity might influence or direct cell function.

PMID- 23138881
TI  - The accuracy of methods for urate crystal detection in synovial fluid and the
      effect of sample handling: a systematic review.
AB  - This study aims to compare different methods of monosodium urate crystal (MSU)
      detection in synovial fluid (SF) and the effect of sample storage and handling on
      crystal detection. A systematic literature search was performed in MEDLINE,
      EMBASE, the Cochrane Library and the American College of Rheumatology/European
      League Against Rheumatism conference abstracts of 2010 and 2011. Studies that
      compared a method for detecting MSU crystals in SF with polarised light
      microscopy (PLM) or compared various SF storage and handling factors with the
      detection of MSU crystals as an outcome were included. Twelve studies out of 247
      identified references were included in the review. Seven studies compared
      different methods of MSU crystal detection in SF with PLM. Due to study
      heterogeneity, methodological limitations and risk of bias, no firm conclusions
      could be drawn from the available data. Five studies examining SF storage and
      handling factors were identified. A reduction in MSU crystal concentration was
      observed over time at room temperature that was not seen in refrigerated samples.
      The use of anticoagulation as a storage medium provided no benefit. Dried
      cytospin preparations appeared to be a suitable medium for long-term storage and
      delayed crystal analysis for at least 12 months. The existing data do not provide
      a compelling argument for the replacement of PLM as the current standard. SF
      sample storage and handling have an effect on MSU crystals and may impact on the
      reliability of analysis.

PMID- 23138882
TI  - Midterm outcome of risedronate therapy for patients with Paget's disease of bone
      in the central part of Japan.
AB  - Although Paget's disease of bone (PDB) is common in western countries, it is
      extremely rare in Asian ones including Japan. Recently, oral risedronate (17.5 mg
      once daily) was approved in Japan as a treatment of PDB besides calcitonin and
      etidronate. However, there are few data regarding the efficacy of this agent,
      dose for patients with PDB in Japan, or the durability of its effect. The purpose
      of this study was to evaluate the midterm outcome of oral risedronate (17.5 mg
      once daily) for patients with PDB in Japan. Seventeen patients with PDB were
      treated with risedronate (17.5 mg once daily) for 8 weeks. Efficacy and its
      durability were accessed based on serum total alkaline phosphatase (ALP) and
      symptoms. Risedronate effectively suppressed bone turnover evaluated with serum
      total ALP in all patients. In 8 of 10 patients with bone pain, risedronate
      reduced the pain. On the other hand, tinnitus and hearing loss did not disappear
      but somewhat improved. None of the patients suffered severe complications. Seven
      of 17 patients required readministration of oral bisphosphonate (risedronate,
      six; alendronate, one) due to elevated total ALP at 27 months (mean ranging from
      9 to 39 months) after the initial administration of risedronate. Treatment of
      oral risedronate (17.5 mg once daily) for 8 weeks is safe and effective for
      patients with PDB in Japan. However, the durability of its effect is limited in
      some patients.

PMID- 23138883
TI  - The effect of dry needling in the treatment of myofascial pain syndrome: a
      randomized double-blinded placebo-controlled trial.
AB  - The objective of this study was to test the hypothesis that dry needling is more
      effective than sham dry needling in the treatment of myofascial pain syndrome
      (MPS). This was a prospective, double-blinded, randomized-controlled study
      conducted in an outpatient clinic. Thirty-nine subjects with established
      myofascial trigger points were randomized into two groups: study group (N = 22)
      and placebo group (N = 17). Dry needling was applied using acupuncture needles,
      and sham dry needling was applied in the placebo group. The treatment was
      composed of six sessions which were performed in 4 weeks; the first four sessions
      were performed twice a week (for 2 weeks) and the last two, once a week (for 2
      weeks). The visual analog scale (VAS) and Short Form-36 (SF-36) were used. When
      compared with the initial values, VAS scores of the dry needling group following
      the first and sixth sessions were significantly lower (p = 0.000 and p < 0.000,
      respectively). When VAS scores were compared between the groups, the first
      assessment scores were found to be similar, but the second and third assessment
      scores were found to be significantly lower in the dry needling group (p = 0.034
      and p < 0.001, respectively). When SF-36 scores of the groups were compared, both
      the physical and mental component scores were found to be significantly increased
      in the dry needling group, whereas only those of vitality scores were found to be
      increased significantly in the placebo (sham needling) group. The present study
      shows that the dry needling treatment is effective in relieving the pain and in
      improving the quality of life of patients with MPS.

PMID- 23138884
TI  - Nodular progression of lentigo malignant melanoma during a treatment with
      tocilizumab: cause or coincidence?
AB  - Tocilizumab is an anti-interleukin (IL)-6 receptor monoclonal antibody, used
      since 2010 for the treatment of severe rheumatoid arthritis (RA). It is known to
      induce infection, similarly to other biotherapies which modulate immune response
      and cytokines. Few cases of malignancy, however, have as yet been reported. We
      describe here the case of a patient with severe RA, previously treated with
      prednisolone, methotrexate, leflunomide, etanercept, and rituximab, who, after 8
      months of treatment with tocilizumab, developed rapidly progressive nodular
      melanoma on a preexisting pigmented lesion on her left cheek. Recently, another
      case of nodular melanoma under tocilizumab has been published. The possible
      causative role of tocilizumab and other immunomodulatory agents in the
      development of this malignancy is discussed. Based on the present case,
      dermatologic screening is recommended before initiation of tocilizumab.

PMID- 23138886
TI  - An estimation of Canadian population exposure to cosmic rays from air travel.
AB  - Based on air travel statistics in 1984, it was estimated that less than 4 % of
      the population dose from cosmic ray exposure would result from air travel. In the
      present study, cosmic ray doses were calculated for more than 3,000 flights
      departing from more than 200 Canadian airports using actual flight profiles.
      Based on currently available air travel statistics, the annual per capita
      effective dose from air transportation is estimated to be 32 MUSv for Canadians,
      about 10 % of the average cosmic ray dose received at ground level (310 MUSv per
      year).

PMID- 23138885
TI  - Integrative proteomic and microRNA analysis of primary human coronary artery
      endothelial cells exposed to low-dose gamma radiation.
AB  - High doses of ionising radiation significantly increase the risk of
      cardiovascular disease (CVD), the vascular endothelium representing one of the
      main targets. Whether radiation doses lower than 500 mGy induce cardiovascular
      damage is controversial. The aim of this study was to investigate radiation
      induced expression changes on protein and microRNA (miRNA) level in primary human
      coronary artery endothelial cells after a single 200 mGy radiation dose (Co-60).
      Using a multiplex gel-based proteomics technology (2D-DIGE), we identified 28
      deregulated proteins showing more than +/-1.5-fold expression change in
      comparison with non-exposed cells. A great majority of the proteins showed up
      regulation. Bioinformatics analysis indicated "cellular assembly and
      organisation, cellular function and maintenance and molecular transport" as the
      most significant radiation-responsive network. Caspase-3, a central regulator of
      this network, was confirmed to be up-regulated using immunoblotting. We also
      analysed radiation-induced alterations in the level of six miRNAs known to play a
      role either in CVD or in radiation response. The expression of miR-21 and miR
      146b showed significant radiation-induced deregulation. Using miRNA target
      prediction, three proteins found differentially expressed in this study were
      identified as putative candidates for miR-21 regulation. A negative correlation
      was observed between miR-21 levels and the predicted target proteins, desmoglein
      1, phosphoglucomutase and target of Myb protein. This study shows for the first
      time that a low-dose exposure has a significant impact on miRNA expression that
      is directly related to protein expression alterations. The data presented here
      may facilitate the discovery of low-dose biomarkers of radiation-induced
      cardiovascular damage.

PMID- 23138888
TI  - Synthesis strategies in the search for hierarchical zeolites.
AB  - Great interest has arisen in the past years in the development of hierarchical
      zeolites, having at least two levels of porosities. Hierarchical zeolites show an
      enhanced accessibility, leading to improved catalytic activity in reactions
      suffering from steric and/or diffusional limitations. Moreover, the secondary
      porosity offers an ideal space for the deposition of additional active phases and
      for functionalization with organic moieties. However, the secondary surface
      represents a discontinuity of the crystalline framework, with a low connectivity
      and a high concentration of silanols. Consequently, hierarchical zeolites exhibit
      a less "zeolitic behaviour" than conventional ones in terms of acidity,
      hydrophobic/hydrophilic character, confinement effects, shape-selectivity and
      hydrothermal stability. Nevertheless, this secondary surface is far from being
      amorphous, which provides hierarchical zeolites with a set of novel features. A
      wide variety of innovative strategies have been developed for generating a
      secondary porosity in zeolites. In the present review, the different synthetic
      routes leading to hierarchical zeolites have been classified into five
      categories: removal of framework atoms, surfactant-assisted procedures, hard
      templating, zeolitization of preformed solids and organosilane-based methods.
      Significant advances have been achieved recently in several of these
      alternatives. These include desilication, due to its versatility, dual templating
      with polyquaternary ammonium surfactants and framework reorganization by
      treatment with surfactant-containing basic solutions. In the last two cases, the
      materials so prepared show both mesoscopic ordering and zeolitic lattice planes.
      Likewise, interesting results have been obtained with the incorporation of
      different types of organosilanes into the zeolite crystallization gels, taking
      advantage of their high affinity for silicate and aluminosilicate species.
      Crystallization of organofunctionalized species favours the formation of organic
      inorganic composites that, upon calcination, are transformed into hierarchical
      zeolites. However, in spite of this impressive progress in novel strategies for
      the preparation of hierarchical zeolites, significant challenges are still ahead.
      The overall one is the development of methods that are versatile in terms of
      zeolite structures and compositions, capable of tuning the secondary porosity
      properties, and being scaled up in a cost-effective way. Recent works have
      demonstrated that it is possible to scale-up easily the synthesis of hierarchical
      zeolites by desilication. Economic aspects may become a significant bottleneck
      for the commercial application of hierarchical zeolites since most of the
      synthesis strategies so far developed imply the use of more expensive procedures
      and reagents compared to conventional zeolites. Nevertheless, the use of
      hierarchical zeolites as efficient catalysts for the production of high value
      added compounds could greatly compensate these increased manufacturing costs.

PMID- 23138889
TI  - Design of a wireless electrochemical valve.
AB  - The control of motion of small objects is an emerging research area. Their design
      strongly depends on the strategy chosen to trigger the locomotion, which is
      typically obtained by either physical or chemical fueling. An ongoing challenge
      in this field is the remote control of the motion with space and time resolution.
      In this context, we describe in the present contribution a wireless
      electrochemical valve based on a chemo-mechanical feedback loop. This valve is
      driven by bipolar electrochemistry and works in aqueous solutions by converting
      reversibly an electrical input signal into periodic motion via electrogenerated
      hydrogen bubbles. We report the design of this very first bipolar valve, together
      with an analysis of the mechanism leading to the energy conversion, based on
      controlled production, storage and release of gas bubbles.

PMID- 23138887
TI  - Genetic incorporation of twelve meta-substituted phenylalanine derivatives using
      a single pyrrolysyl-tRNA synthetase mutant.
AB  - When coexpressed with its cognate amber suppressing tRNACUAPyl(CUA), a
      pyrrolysyltRNA synthetase mutant N346A/C348A is able to genetically incorporate
      12 meta-substituted phenylalanine derivatives into proteins site-specifically at
      amber mutation sites in Escherichia coli. These genetically encoded noncanonical
      amino acids resemble phenylalanine in size and contain diverse bioorthogonal
      functional groups such as halide, trifluoromethyl, nitrile, nitro,ketone, alkyne,
      and azide moieties. The genetic installation of these functional groups in
      proteins provides multiple ways to site-selectively label proteins with
      biophysical and biochemical probes for their functional investigations. We
      demonstrate that a genetically incorporated trifluoromethyl group can be used as
      a sensitive 19F NMR probe to study protein folding/unfolding, and that
      genetically incorporated reactive functional groups such as ketone,alkyne, and
      azide moieties can be applied to site-specifically label proteins with
      fluorescent probes. This critical discovery allows the synthesis of proteins with
      diverse bioorthogonal functional groups for a variety of basic studies and
      biotechnology development using a single recombinant expression system.

PMID- 23138890
TI  - A revolutionary design change to improve stapler safety.
AB  - BACKGROUND: Postoperative staple line leaks and bleeding are the most common
      reasons for complications in surgical procedures that involve organ resection,
      such as sleeve gastrectomy. Increasing the safety of these operations requires
      improving the instruments (endostaplers or endocutters) used for stapling and
      sectioning the tissues. METHODS: We present a new prototype stapler for marketing
      in resection surgery, especially designed for the sleeve gastrectomy. RESULTS: We
      suggest that the medical instrument industry creates devices in which the channel
      along which the knife blade runs is located asymmetrically. This would allow more
      staples to be placed on the side of the gastric remnant, thus improving the
      sealing and hemostasis of the suture line and reducing the number of
      complications for patients as a result. CONCLUSIONS: The application of new
      concepts in medical surgical devices can improve the safety of the procedures in
      our patients.

PMID- 23138891
TI  - The ICH S5(R2) guideline for the testing of medicinal agents.
AB  - Relying on previous regulatory guidelines from multiple countries, the ICH S5(R2)
      guideline outlines the preclinical safety studies needed for registration of new
      medicinal products in the member countries (European Union, Japan, and the United
      States). The primary purpose of the guideline is to provide a testing strategy to
      detect and reveal toxicity to the reproductive system including development of
      the embryo. There are basically three study designs outlined by the guidance,
      assessment of fertility in adults, pre- and postnatal development of exposed
      offspring, and morphological evaluation following exposure during major
      organogenesis. This chapter discusses the major points addressed in the guidance
      for each study type, and points to additional references that discuss the
      practical details for conducting such studies.

PMID- 23138892
TI  - Nonclinical reproductive toxicity testing requirements for drugs, pesticides, and
      industrial chemicals in India and China.
AB  - India and China have booming chemical, agrochemical, and pharmaceutical
      industries. Both countries also represent expanding markets for foreign chemical
      and healthcare companies. All such products require reproductive toxicity testing
      before marketing. The ICH testing guidelines for medicinal products are not
      applicable in China and India. Nonetheless, reproductive toxicity studies
      designed and run to ICH principles are generally acceptable for submission. The
      Chinese guidelines take into consideration traditional Chinese medicines, which
      are usually mixtures. Likewise, the specific recommendations of India and China
      for the reproductive toxicity testing of chemicals and pesticides differ from
      those of the OECD and the USEPA. Again, studies performed in accordance with
      internationally recognized principles are usually acceptable for submission in
      both countries. The Chinese guideline for the reproductive toxicity testing of
      agrochemicals is currently under revision; the new version is expected to
      resemble more closely the requirements of the OECD and the USEPA. As a member of
      the OECD, India has conducted Good Laboratory Practice (GLP) inspection,
      accreditation, and monitoring activities since 2004. China has made several
      attempts to join the Council Decisions on Mutual Acceptance of Data in the
      Assessment of Chemicals since 2005. Currently 47 laboratories in China have been
      certified by the national GLP authorities. Several laboratories in China have
      also been recently been certified by OECD member countries as GLP compliant. In
      India, there are currently 23 GLP-Certified laboratories; about six of these are
      also AALAC accredited. The specific study designs specified in the guidelines of
      China and India for reproductive toxicity studies are described in detail in this
      chapter.

PMID- 23138893
TI  - The developmental toxicity testing of biologics.
AB  - The characteristics of biologic drugs, as compared with small molecules, confer
      significant advantages for both the drug developer and the prospective patients.
      The necessity for, and the timing of, developmental toxicity testing in the
      preclinical program must be considered. Choice of an appropriate test system is
      of particular importance, one that shows pharmacodynamic activity comparable to
      man. Where the conventional rodent/non-rodent species show such functional cross
      reactivity, those species can be used in developmental testing, but often the
      only relevant species will be a nonhuman primate, in which case an extended study
      design (the ePPND) should be the default. Such an approach provides appropriate
      toxicity screening while reducing animal usage.

PMID- 23138894
TI  - The OECD guidelines for the testing of chemicals and pesticides.
AB  - In many countries the process of toxicity testing of environmental chemicals is
      ruled by a framework of OECD guidelines. The present paper will give an overview
      over the relevant OECD guidelines and guidance documents and mainly focus on
      methodological issues related to the prenatal toxicity testing guideline.
      Relevant guideline text will be provided, and practical recommendations will be
      given both for critical issues of experimental methodology and data
      interpretation.

PMID- 23138895
TI  - Teratology testing under REACH.
AB  - REACH guidelines may require teratology testing for new and existing chemicals.
      This chapter discusses procedures to assess the need for teratology testing and
      the conduct and interpretation of teratology tests where required.

PMID- 23138896
TI  - The teratology testing of food additives.
AB  - The developmental and reproductive toxicity testing (including teratogenicity) of
      new foods and food additives is performed worldwide according to the guidelines
      given in the FDA Redbook. These studies are not required for substances that are
      generally recognized as safe, according to the FDA inventory. The anticipated
      cumulated human exposure level above which developmental or reproduction studies
      are required depends on the structure-alert category. For food additives of
      concern, both developmental (prenatal) and reproduction (multigeneration) studies
      are required. The developmental studies are performed in two species, usually the
      rat and the rabbit. The reproduction study is generally performed in the rat. The
      two rat studies are preferably combined into a single experimental design, if
      possible. The test methods described in the FDA Redbook are similar to those
      specified by the OECD for the reproductive toxicity testing of chemicals.

PMID- 23138897
TI  - Developmental toxicity testing of vaccines.
AB  - Preventative and therapeutic vaccines are increasingly used during pregnancy and
      present special considerations for developmental toxicity testing. The various
      components of the vaccine formulation (i.e., protein or polysaccharide antigen,
      adjuvants, and excipients) need to be assessed for direct effects on the
      developing conceptus. In addition, possible adverse influences of the induced
      antibodies on fetal and/or postnatal development need to be evaluated. A guidance
      document on the preclinical testing of preventative and therapeutic vaccines for
      developmental toxicity was issued by the FDA in 2006. Preclinical studies are
      designed to assess possible influences of vaccines on pre- and postnatal
      development. The choice of model animal for these experiments is influenced by
      species differences in the timing and extent of the transfer of the induced
      maternal antibodies to the fetus. The cross-placental transport of maternal
      immunoglobulins generally only occurs in late gestation and tends to be greater
      in humans and monkeys than in non-primate species. For many vaccines, the rabbit
      shows a greater rate of prenatal transfer of the induced antibodies than rodents.
      For biotechnology-derived vaccines that are not immunogenic in lower species,
      nonhuman primates may be the only appropriate models. It may be advisable to test
      new adjuvants using the ICH study designs for conventional pharmaceuticals in
      addition to the developmental toxicity study with the final vaccine formulation.

PMID- 23138898
TI  - The teratology testing of cosmetics.
AB  - In Europe, the developmental toxicity testing (including teratogenicity) of new
      cosmetic ingredients is performed according to the Cosmetics Directive
      76/768/EEC: only alternatives leading to full replacement of animal experiments
      should be used. This chapter presents the three scientifically validated animal
      alternative methods for the assessment of embryotoxicity: the embryonic stem cell
      test (EST), the micromass (MM) assay, and the whole embryo culture (WEC) assay.

PMID- 23138899
TI  - Teratology studies in the rat.
AB  - The rat is the rodent species of choice for the regulatory safety testing of
      xenobiotics, such as medicinal products, food additives, and other chemicals.
      Many decades of experience and extensive data have accumulated for both general
      and developmental toxicology investigations in this species. The high fertility
      and large litter size of the rat are advantages for teratogenicity testing. The
      study designs are well defined in the regulatory guidelines and are relatively
      standardized between testing laboratories across the world. Teratology studies
      address maternal- and embryo-toxicity following exposure during the period of
      organogenesis. This chapter describes the design and conduct of a teratology
      study in the rat in compliance with the regulatory guidelines. The procedures for
      the handling and housing of the pregnant animals, the caesarean examinations and
      the sampling of fetuses for morphological examinations are described. The utility
      and design of preliminary studies and the inclusion of satellite animals in the
      main study for toxicokinetic sampling are discussed.

PMID- 23138900
TI  - Teratology studies in the mouse.
AB  - The rat is the routine species of choice as the rodent model for regulatory
      safety testing of xenobiotics such as medicinal products, food additives, and
      other chemicals. However, the rat is not always suitable for pharmacological,
      toxicological, immunogenic, pharmacokinetic, or even practical reasons. Under
      such circumstances, the mouse offers an alternative for finding a suitable rodent
      model acceptable to the regulatory authorities. Since all essential routes of
      administration are possible, the short reproductive cycle and large litter size
      of the mouse make it a species well adapted for use in teratology studies. Given
      that good quality animals, including virgin mated females, can be acquired
      relatively easily and inexpensively, the mouse has been used in reproductive
      toxicity studies for decades and study protocols are well established.

PMID- 23138901
TI  - Combined fertility and embryotoxicity study.
AB  - Under normal circumstances, fertility and embryotoxicity studies are run
      separately according to the ICH S5(R2) guideline for the detection of toxicity to
      reproduction of medicinal products (1). However, the flexible approach of the
      S5(R2) guideline also allows the reproduction stages covered in the fertility and
      embryo-fetal development studies (stages A to D) to be combined into a single
      study design. The administration period covers the pre-mating and gestation
      phases through to closure of the hard palate. The principal advantages of the
      combined study include reductions in the number of animals required and cost.
      Although the rat is the routine species of choice, the mouse may also be used.

PMID- 23138902
TI  - Teratology studies in the rabbit.
AB  - The rabbit is generally the non-rodent species or second species after the rat
      recommended by the regulatory authorities and is part of the package of
      regulatory reproductive studies for the detection of potential embryotoxic and/or
      teratogenic effects of pharmaceuticals, chemicals, food additives, and other
      compounds, including vaccines (see Chapters 1-7).Its availability, practicality
      in housing and in mating as well as its large size makes the rabbit the preferred
      choice as a non-rodent species. The study protocols are essentially similar to
      those established for the rat (Chapter 9), with some particularities. The study
      designs are well defined in guidelines and are relatively standardized between
      testing laboratories across the world.As for the rat, large litter sizes and
      extensive background data in the rabbit are valuable criteria for an optimal
      assessment of in utero development of the embryo or fetus and for the detection
      of potential external or internal fetal malformations.

PMID- 23138903
TI  - Teratology studies in the minipig.
AB  - The minipig is a suitable species for regulatory teratology testing and may be
      regarded as an alternative to the rabbit, dog, and primate. The first successful
      regulatory teratology studies in the minipig were performed in the 1990s. It
      became clear that minipigs have several benefits over the other non-rodents, as
      they are purpose-bred for laboratory use, they are sexually mature at
      approximately 5 months of age, and they produce multiple offspring. The minipig
      has subsequently gained regulatory acceptance in the teratology testing of new
      drugs.

PMID- 23138904
TI  - Embryo fetal development studies in nonhuman primates.
AB  - Embryo fetal development (EFD) studies in nonhuman primates are frequently
      conducted in macaques with Macaca fascicularis (cynomolgus monkey, long-tailed
      macaque, crab-eating macaque) being the most accepted model. EFD studies are also
      feasible in the marmoset. Due to recent guideline changes (ICH M3(R2) and
      S6(R1)), EFD studies are largely confined to conventional pharmaceutical
      compounds rather than biopharmaceuticals. This chapter describes basic study
      designs and provides working protocols for collecting, processing, and staining
      fetuses, including collection of amniotic fluid and umbilical cord blood. The
      chapter also covers the examination and terminology for external, visceral, and
      skeletal examinations of fetuses. The species covered in this chapter are
      cynomolgus monkey (long-tailed macaque) and marmoset monkey.

PMID- 23138905
TI  - The enhanced pre- and postnatal development study for monoclonal antibodies.
AB  - The enhanced pre- and postnatal (ePPND) study design has been developed in
      response to new scientific knowledge and subsequent guideline changes [ICH M3(R2)
      and ICH S6(R1)]. The changes in study design were basically driven by the
      experiences obtained during preclinical development of biopharmaceuticals. The
      standard ePPND concept does not apply to conventional small molecule
      pharmaceuticals. In essence, the ePPND design is a pre- and postnatal development
      (PPND) study in which key elements of an embryo-fetal development study are
      investigated in newborns and infants rather than in the fetus. The cynomolgus
      monkey is the current relevant nonhuman primate model. The ICH S6(R1) guideline
      reached step 5 in June 2011 and provides detailed recommendations on various
      parameters and the conduct of an ePPND study. This chapter provides working
      guidance for monitoring menstrual cycles to generate pregnant animals, ultrasound
      monitoring of pregnancy, morphometric measurements of fetuses and newborns, in
      vivo skeletal examination, various protocols for evaluation of infants (e.g.,
      neurobehavioral assessment, learning and memory test, grip strength, immune
      system evaluation) and a comprehensive list of additional infant evaluation
      parameters for the cynomolgus monkey.

PMID- 23138906
TI  - Skeletal examination by alizarin staining.
AB  - A skeletal examination of fetuses is required in regulatory embryo-fetal
      development studies. This chapter describes a method of skeletal examination
      using alizarin staining. All fetuses are removed from the mother by caesarean
      section before birth. The fetuses are first examined externally. For larger
      species (rabbit and minipig), an internal examination can be performed on the
      fresh soft tissues by microdissection. For smaller species, such as the rat and
      mouse, half of each litter is fixed for internal soft tissue examination. The
      other half is used for skeletal examination. A rapid examination of the fresh
      soft tissues is performed before evisceration and fixation. The staining process
      takes several days. Following staining, all bones are examined from the head to
      the tail, in ventral and dorsal positions.

PMID- 23138907
TI  - Skeletal examination by double staining for ossified bone and cartilaginous
      tissue.
AB  - The assessment of developmental toxicology data is a critical aspect of hazard
      evaluation for pharmaceuticals and environmental chemicals. Skeletal examination
      is an essential part of prenatal developmental toxicity studies of chemicals as
      well as pesticides and comprises evaluation of both cartilaginous and ossified
      skeletal components. Various techniques are published in the literature to
      process and double-stain skeletons of common laboratory animals which are all
      based on staining of the cartilage with Alcian Blue and staining of ossified
      bones with Alizarin Red S along with maceration (clearing) of the surrounding
      soft tissue. The staining of the cartilage allows the examination to assess
      ossified structures and their underlying cartilage in a single step.

PMID- 23138908
TI  - Small animal imaging and examination by micro-CT.
AB  - Micro-computed tomography imaging technology allows for the whole-mount
      investigation of skeletal structures in preclinical specimens at both fetal and
      postnatal time points. The imaging process is nondestructive to the specimen and
      can be performed at various resolutions to derive the region of interest
      information most relevant to individual researchers. In addition to qualitative
      imaging of skeletal samples, accurate and desirable metrics such as bone mineral
      density (BMD), discrete cortical and trabecular bone analysis, and milligrams
      hydroxyapatite per unit volume (mgHA/cc) are also achievable depending upon
      scanner platform. Additional benefits to the method include digitally archivable
      files, in vivo and ex vivo scanning options, and volumetric or slice-thru
      presentation of data in standard histological or oblique orientations. Some
      drawbacks to the method include long scan times at higher spatial resolutions,
      large file sizes, and limitation to imaging of highly dense biological structures
      (i.e., bone), though several groups have attempted to expand the modality to
      include soft tissue imaging in ex vivo specimens.

PMID- 23138909
TI  - Fetal soft tissue examination by serial sectioning.
AB  - This chapter describes the method used for serial sectioning and soft tissue
      examination of the Bouin's fixed fetus (mainly whole rat and or mouse fetuses or
      rabbit fetal heads) for the assessment of developmental and structural
      abnormalities. Fetuses are examined externally, together with the internal
      structures of the head as well as the thoracic and abdominal organs.

PMID- 23138910
TI  - Fetal soft tissue examinations by microdissection.
AB  - This chapter describes methods for the examination of fetal abdominal and
      thoracic soft tissues by microdissection on either fresh (non-rodent) or fixed
      (rodent) specimens in order to detect structural abnormalities. With hundreds of
      fetuses examined for each species (rodent and non-rodent) in regulatory
      reproductive toxicity assessments (ICH,
      http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Multidiscipl
      nary/M3_R2/Step4/M3_R2__Guideline.pdf, 2009; ICH,
      http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Safety/S5_R2
      Step4/S5_R2__Guideline.pdf, 2005), microdissection techniques allow a thorough
      and relatively rapid examination of fetuses for soft tissue abnormalities.

PMID- 23138911
TI  - Soft tissue examination of the fetal rat and rabbit head by magnetic resonance
      imaging.
AB  - The use of magnetic resonance imaging of the fetal rat and rabbit head, as an
      alternative to the traditional methods of fixation and preparation of serial
      sections, is described. Labeled magnetic resonance images of normal head anatomy
      have been provided as a reference for use when evaluating the internal structures
      of the head.

PMID- 23138912
TI  - Historical control data in reproductive and developmental toxicity studies.
AB  - Reproductive and developmental toxicity studies in laboratory animals are
      conducted as part of the process of evaluating the risk of pharmaceuticals and
      chemicals to human reproduction and development. In these studies, comparison of
      data from groups dosed with the test article to a concurrent control group is
      considered the most relevant approach for the interpretation of adverse effects.
      However, differences between the concurrent control and treated groups may arise
      by chance alone, and in some instances may even appear to be dose-related. These
      limitations of the concurrent control group are of particular concern when
      interpreting fetal malformation data because malformations are rare events that
      can be better characterized when incidences in both concurrent control and
      treated groups are compared to a larger set of control values. Historical control
      data can be useful not only to understand the range of normal for a given
      endpoint but also to monitor the biological variability over time due to various
      external factors (e.g., genetic changes in a strain, changes at the breeding
      facility). It can also serve to track the performance of the laboratory and
      identify any changes in the data that may be the result of internal factors at
      the performing laboratory due to modification in animal diet, seasonal changes,
      or even the proficiency of the technicians in handling animals and recording
      fetal and offspring observations. This chapter will provide the reader with
      guidance on building a laboratory historical control database and applying it to
      the scientific interpretation of reproductive and developmental toxicity data.
      Information on sources of external historical control data will be provided and
      some perspective given on the utility of this data. A discussion of the
      presentation of historical control data with descriptive statistics will be
      accompanied by examples of tabulation of the data. Supernumerary rib will be used
      as an example of how historical control data can be used for data interpretation.

PMID- 23138913
TI  - Reporting of teratology studies.
AB  - The regulatory toxicology report is an unusual document that requires a
      particular skill to write. The report must be clear, accurate, concise, and
      focused. A clear and direct writing style is required. The end-users of the
      report will hope to find the information they seek with as little effort as
      possible. Few, or none, will read the entire document. The author should aim to
      appease the user by obliging him to read as little text and turn as few pages as
      possible. This chapter gives tips and guidance on how to present the experimental
      data and write the narrative text in the final study report for a teratology
      study.

PMID- 23138914
TI  - Maternal toxicity.
AB  - Although demonstration of some degree of maternal toxicity is required in
      regulatory developmental toxicology studies, marked maternal toxicity may be a
      confounding factor in data interpretation. Reduction in maternal body weight gain
      is the far most frequently used endpoint of toxicity, but alternative endpoints,
      like organ toxicity or exaggerated pharmacological response, can also be taken
      into consideration. The following conclusions are based on literature data and
      discussions at maternal toxicity workshops attended by representatives from
      regulatory agencies, academia, and industry: (1) Available results do not support
      that maternal toxicity (defined as clinical signs, decreased body weight gain or
      absolute body weight loss of up to 15% in rats or 7% in rabbits) can be used to
      explain the occurrence of major malformations. (2) There is clear evidence that
      substantial reductions in maternal weight gain (or absolute weight loss) are
      linked with other manifestations of developmental toxicity. Among these can be
      mentioned decreased fetal weight, and skeletal anomalies (e.g., wavy ribs) in
      rats and decreased fetal weights, post implantation loss, abortions, and some
      skeletal anomalies in rabbits. (3) There are several examples of
      misinterpretation among companies, where it was incorrectly expected that
      regulatory authorities would not label chemicals/drugs as
      "teratogens/developmental toxicants" because embryo fetal adverse effects were
      only observed at doses also causing signs of maternal toxicity. (4) Similarly,
      even if mechanistic studies indicate that a substance causes developmental
      toxicity via exaggerated pharmacological effects in the mother, such a mechanism
      does not automatically negate the observed fetal adverse effects.From a
      regulatory perspective, an observed developmental toxic finding is considered to
      be of potential human relevance (even if it is mediated via maternal
      pharmacological effects or occur at doses causing signs of maternal toxicity)
      unless the company can provide appropriate mechanistic and/or other convincing
      evidence to the contrary.

PMID- 23138915
TI  - Innovations in testing strategies in reproductive toxicology.
AB  - Toxicological hazard assessment currently finds itself at a crossroads where the
      existing classical test paradigm is challenged by a host of innovative
      approaches. Animal study protocols are being enhanced for additional parameters
      and improved for more efficient effect assessment with reduced animal numbers.
      Whilst existing testing paradigms have generally proven conservative for chemical
      safety assessment, novel alternative in silico and in vitro approaches and assays
      are being introduced that begin to elucidate molecular mechanisms of toxicity.
      Issues such as animal welfare, alternative assay validation, endocrine
      disruption, and the US-NAS report on toxicity testing in the twenty-first century
      have provided directionality to these developments. The reductionistic nature of
      individual alternative assays requires that they be combined in a testing
      strategy in order to provide a complete picture of the toxicological profile of a
      compound. One of the challenges of this innovative approach is the combined
      interpretation of assay results in terms of toxicologically relevant effects.
      Computational toxicology aims at providing that integration. In order to
      progress, we need to follow three steps: (1) Learn from past experience in animal
      studies and human diseases about critical end points and pathways of toxicity.
      (2) Design alternative assays for essential mechanisms of toxicity. (3) Build an
      integrative testing strategy tailored to human hazard assessment using a battery
      of available alternative tests for critical end points that provides optimal in
      silico and in vitro filters to upgrade toxicological hazard assessment to the
      mechanistic level.

PMID- 23138916
TI  - Predictive models and computational toxicology.
AB  - Understanding the potential health risks posed by environmental chemicals is a
      significant challenge elevated by the large number of diverse chemicals with
      generally uncharacterized exposures, mechanisms, and toxicities. The ToxCast
      computational toxicology research program was launched by EPA in 2007 and is part
      of the federal Tox21 consortium to develop a cost-effective approach for
      efficiently prioritizing the toxicity testing of thousands of chemicals and the
      application of this information to assessing human toxicology. ToxCast addresses
      this problem through an integrated workflow using high-throughput screening (HTS)
      of chemical libraries across more than 650 in vitro assays including biochemical
      assays, human cells and cell lines, and alternative models such as mouse
      embryonic stem cells and zebrafish embryo development. The initial phase of
      ToxCast profiled a library of 309 environmental chemicals, mostly pesticidal
      actives having rich in vivo data from guideline studies that include
      chronic/cancer bioassays in mice and rats, multigenerational reproductive studies
      in rats, and prenatal developmental toxicity endpoints in rats and rabbits. The
      first phase of ToxCast was used to build models that aim to determine how well in
      vivo animal effects can be predicted solely from the in vitro data. Phase I is
      now complete and both the in vitro data (ToxCast) and anchoring in vivo database
      (ToxRefDB) have been made available to the public (http://actor.epa.gov/). As
      Phase II of ToxCast is now underway, the purpose of this chapter is to review
      progress to date with ToxCast predictive modeling, using specific examples on
      developmental and reproductive effects in rats and rabbits with lessons learned
      during Phase I.

PMID- 23138917
TI  - The embryonic stem cell test.
AB  - The embryonic stem cell test is an animal-free alternative test method for
      developmental toxicity. Mouse embryonic stem cells are cultured in a hanging drop
      method to form embryoid bodies. These embryoid bodies, when plated on tissue
      culture dishes, differentiate to form contracting myocardial cell foci within 10
      days. Inhibition of cardiomyocyte differentiation by test compounds serves as the
      end point of the assay, as monitored by counting contracting muscle foci under
      the microscope.

PMID- 23138918
TI  - Zebrafish teratogenicity testing.
AB  - As a model for teratogenicity research, zebrafish are gaining popularity and
      creditability. Zebrafish embryos have been proven to be a highly valuable tool in
      genetics and developmental biology research and have advanced our understanding
      of a number of known developmental toxicants. It has yet to be determined
      conclusively how reliably a zebrafish embryo screening assay predicts what will
      happen in mammalian models, but results from initial assessments have been
      encouraging. Here we have presented procedures for the basic care of a zebrafish
      colony to support embryo production, embryo collection and culturing, and
      teratogenicity experiments.

PMID- 23138919
TI  - Frog embryo teratogenesis assay on Xenopus and predictivity compared with in vivo
      mammalian studies.
AB  - Frog embryo teratogenesis assay on Xenopus (FETAX) has been routinely used in our
      laboratory for the last 12 years as a routine developmental toxicity screening
      test for pharmaceutical candidate compounds. To date, out of more than 400
      candidates tested in FETAX, around 60 have also been evaluated in mammalian
      embryotoxicity studies according to standard ICH protocols.Compound teratogenic
      potential in both FETAX and mammalian embryotoxicity studies is determined after
      analysis of the developmental toxicity characterized by embryotoxicity, growth
      delay, and/or potential to induce malformations. Based on this experience, the
      predictivity of FETAX is 81% with a minimal proportion of false positive results.

PMID- 23138920
TI  - The rat whole embryo culture assay using the Dysmorphology Score system.
AB  - The rat whole embryo culture (WEC) system has been used extensively for
      characterizing teratogenic properties of test chemicals. In this chapter, we
      describe the methodology for culturing rat embryos as well as a new morphological
      score system, the Dysmorphology Score (DMS) system for assessing morphology of
      mid gestation (gestational day 11) rat embryos. In contrast to the developmental
      stage focused scoring associated with the Brown and Fabro score system, this new
      score system assesses the respective degree of severity of dysmorphology, which
      delineates normal from abnormal morphology of specific embryonic structures and
      organ systems. This score system generates an approach that allows rapid
      identification and quantification of adverse developmental findings, making it
      conducive for characterization of compounds for teratogenic properties and
      screening activities.

PMID- 23138921
TI  - Toxicogenomic approaches in developmental toxicology testing.
AB  - The emergence of toxicogenomic applications provides new tools to characterize,
      classify, and potentially predict teratogens. However, due to the vast number of
      experimental and statistical procedural steps, toxicogenomic studies are
      challenging. Here, we guide researchers through the basic framework of conducting
      toxicogenomic investigations in the field of developmental toxicology, providing
      examples of biological and technical factors that may influence response and
      interpretation. Furthermore, we review current, diverse applications of
      toxicogenomic-based approaches in teratology testing, including exposure-response
      characterization (dose and duration), chemical classification studies, and cross
      model comparisons study designs. This review is intended to guide scientists
      through the challenging and complex structure of conducting toxicogenomic
      analyses, while considering the many applications of using toxicogenomics in
      study designs and the future of these types of "omics" approaches in
      developmental toxicology.

PMID- 23138922
TI  - Validation of alternative tests for developmental and reproductive toxicology
      testing: an ILSI Health and Environmental Sciences Institute perspective.
AB  - The current political and societal climate is driving the science of toxicology
      towards developing non-animal testing methodologies. Though alternative and in
      vitro tests have always been a mainstay for toxicological testing, technological
      advances in the last decade have allowed toxicologists to move rapidly towards a
      better understanding of the relevance of in vitro endpoints for traditional
      apical endpoints. Non-animal research using new technologies have illuminated
      toxicologists on the mechanisms of protection and adverse health outcomes. In
      this context, the "validation" of alternative and in vitro tests has taken on
      significant importance, particularly in regard to satisfying safety concerns of
      drugs and chemicals in a regulatory setting. The purpose of this chapter is to
      briefly review the impetus for the development of alternative and in vitro tests,
      discuss the projects underway at the ILSI Health and Environmental Sciences
      Institute (HESI) that are oriented towards this topic, and summarize the
      processes for formal validation. It should be noted that though there are
      validated assays and tests, these are under constant evaluation by scientific
      researchers as our understanding of the underlying biological processes continues
      to evolve.

PMID- 23138923
TI  - Regulatory assessment of reproductive toxicology data.
AB  - This chapter outlines a regulator's personal approach to the assessment of
      reproductive toxicology data in the context of the assessment of the overall
      nonclinical data package for pharmaceutical agents. Using as a framework the
      International Conference on Harmonisation Common Technical Document headings,
      guidance is provided on the expectations of regulators for the presentation and
      discussion of the data by the applicant to facilitate the risk assessment
      process. Consideration is given to the use of reproductive toxicology data in the
      assessment process for both clinical trial applications (CTAs) and marketing
      authorization applications (MAAs). Suggestions for some guiding principles in
      drafting of the various product information documents (for example the
      Investigator's Brochure (IB) for CTAs and the Nonclinical Overview and Summary of
      Product Characteristics for MAAs) are included.

PMID- 23138924
TI  - Hazard and risk assessment of teratogenic chemicals under REACH.
AB  - In 2007, a new European chemicals legislation was implemented: Regulation (EC)
      No. 1907/2006, also known as "REACH." It obliges companies to take the main
      responsibility for the valid information on the safe use of the chemicals they
      manufacture and/or place on the European market. So they must, for example,
      register their chemicals at the European Chemicals Agency (ECHA) and submit
      extensive substance-related registration dossiers containing information on the
      substances' intrinsic hazardous properties and documentation of their risk
      assessment. REACH regulates the registration and evaluation process as well as
      the authorization and restriction procedure. In addition, classification,
      labeling, and packaging of chemicals apply in accordance with Regulation (EC) No.
      1272/2008 ("CLP Regulation"). It implements almost completely the provisions of
      the United Nations Globally Harmonised System of Classification and Labelling of
      Chemicals (UN GHS) into European legislation and will fully replace the Dangerous
      Substances Directive (67/548/EEC) and the Dangerous Preparations Directive
      (1999/45/EC) by 2015. According to both the old and the new classification
      system, teratogenic chemicals are classified as developmental toxicants, with
      developmental toxicity falling within the hazard class of reproductive toxicity.
      REACH as well as the CLP Regulation provide several procedures in which
      reproductive toxicants take a special position because their harmful effects are
      considered particularly serious. Teratogenic substances are not explicitly named
      by these legal texts but, as they constitute as developmental toxicants a hazard
      differentiation of reproductive toxicity, they are implicitly always included by
      the provisions.

PMID- 23138925
TI  - Reproductive toxicity risk assessment for pesticides.
AB  - Human health risk assessment for pesticides is based mainly on animal studies
      submitted by the applicant and aims to determine safe exposure levels for
      operators (farmers and agricultural workers) and consumers of all age groups.
      Critical effects, including those resulting from reproductive toxicity, are
      identified during hazard assessment from an evaluation of all studies in the
      toxicity package. Reproductive or developmental effects are considered critical
      if they are more severe or occur at lower doses than other toxicities. Reference
      values for human exposure are then derived from No Adverse Effect Levels for the
      relevant critical effects by applying safety factors. This paper describes
      methods and caveats applicable to the evaluation of prenatal toxicity and two
      generation studies from the view of a regulator, stressing the importance of
      individual litter data and the relationship between different endpoints.

PMID- 23138926
TI  - The thalidomide disaster, lessons from the past.
AB  - It is close to 60 years since thalidomide was created by the German company,
      Chemie-Grunenthal, and launched as "Contergan." This was soon to be followed in
      England by the launch of "Distaval." Of all the drugs developed in the
      intervening years, thalidomide has undoubtedly had the greatest influence on
      shaping the Pharmaceutical Industry as we know it today.Strong marketing pressure
      in an Industry hungry for new medicines brought an inadequately tested drug to
      the market, targeted outsourcing quickly expanded the client base and finally
      market forces prevented timely withdrawal, even when evidence was emerging of
      disastrous side-effects. The full story of thalidomide was told by the Sunday
      Times in "Suffer The Children" (Kingsley et al., Suffer the children: the story
      of thalidomide, the insight team of the Sunday times (UK), 1979).Many
      preventative measures have been taken in the intervening years in light of the
      lessons learned with thalidomide. However, many of the pressures that led to the
      thalidomide disaster exist today with record high management and shareholder
      pressures to achieve success, parallel worldwide marketing, increased numbers of
      targeted outsourcing by small companies forming alliances with "Big Pharma" and,
      according to some commentators, a breakdown in the system of checks and balances
      that have existed in the regulatory authorities in the intervening years.Using
      thalidomide as a point of reference, this chapter looks at drug development and
      testing, regulatory authorities and guidelines, outsourcing and in-licensing,
      pharmacovigilance, and factors that influence withdrawal of a drug from the
      market.

PMID- 23138928
TI  - Negative regulation of NEP expression by hypoxia.
AB  - BACKGROUND: Neutral endopeptidase (NEP) is a transmembrane cell surface peptidase
      present on prostatic epithelial cells that catalytically inactivates small
      peptide substrates. Neutral endopeptidase loss is associated with prostate cancer
      growth, progression, and increased angiogenesis. We examined whether NEP
      expression is regulated by hypoxia, frequently encountered in the tumor
      microenvironment. METHODS: NEP expression was compared in prostate cancer cell
      lines cultured in normoxic and hypoxic conditions. The NEP activity, protein
      levels, and mRNA levels were determined using enzyme assay, Western blotting and
      q-PCR analysis, respectively. Electrophoretic mobility shift assay and chromatin
      immunoprecipitation assay (ChIP) was used to confirm the negative regulation of
      NEP at the transcriptional level by hypoxia responsive elements (HREs). RESULTS:
      The results indicate that NEP expression was inhibited under hypoxic conditions
      in the NEP positive LNCaP, C4-2, and 22RV1 cells and human umbilical vascular
      endothelial (HUVEC) cells. NEP regulation appeared to be predominantly at the
      transcriptional level as NEP mRNA expression significantly reduced with hypoxia,
      concordant with the kinetics of protein levels, and NEP enzyme activity. A search
      of the NEP gene sequence revealed three putative HREs upstream of the NEP
      promoter. Two of the HREs demonstrated a specific reduction of shift in the
      presence of cobalt chloride; specificity of the binding sites was confirmed by
      ChIP. CONCLUSIONS: Our data indicate a novel mechanism where hypoxia negatively
      regulates the tumor suppressor function of NEP in prostate cancer. The negative
      regulation of NEP is mediated by binding of the HIF1-alpha protein binding to the
      HREs present upstream of the NEP promoter.

PMID- 23138927
TI  - MicroRNAs in brain metastases: big things come in small packages.
AB  - Metastatic brain tumors provide a formidable obstacle in the survival of affected
      cancer patients, an obstacle that current treatment is essentially ineffective
      against. Our understanding of the metastatic cascade has demonstrated the role of
      incorrectly regulated protein expression and proved it to be a crucial component
      of this process. Recently, molecular studies have emphasized the role of
      microRNAs, small non-coding RNAs that alter protein expression, in the regulation
      of both normal and abnormal biological processes, including cancer and its
      metastasis to the brain. Furthermore, studies have demonstrated the ability to
      distinguish normal from cancerous cells, primary from secondary brain tumors, and
      correctly categorize metastatic brain tumor tissue of origin based solely on
      microRNA profiles. Interestingly, manipulation of microRNAs has proven effective
      in cancer treatment. With the promise of reduced toxicity, increased efficacy,
      and individually directed therapy, using microRNA in the treatment of metastatic
      brain tumors may prove very useful. In this review, we focus on the multiple
      potential microRNA targets for the treatment of metastatic brain lesions as well
      as current and future directions for its use in gene therapy.

PMID- 23138929
TI  - Robust 2D/3D registration for fast-flexion motion of the knee joint using hybrid
      optimization.
AB  - Previously, we proposed a 2D/3D registration method that uses Powell's algorithm
      to obtain 3D motion of a knee joint by 3D computed-tomography and bi-plane
      fluoroscopic images. The 2D/3D registration is performed consecutively and
      automatically for each frame of the fluoroscopic images. This method starts from
      the optimum parameters of the previous frame for each frame except for the first
      one, and it searches for the next set of optimum parameters using Powell's
      algorithm. However, if the flexion motion of the knee joint is fast, it is likely
      that Powell's algorithm will provide a mismatch because the initial parameters
      are far from the correct ones. In this study, we applied a hybrid optimization
      algorithm (HPS) combining Powell's algorithm with the Nelder-Mead simplex (NM
      simplex) algorithm to overcome this problem. The performance of the HPS was
      compared with the separate performances of Powell's algorithm and the NM-simplex
      algorithm, the Quasi-Newton algorithm and hybrid optimization algorithm with the
      Quasi-Newton and NM-simplex algorithms with five patient data sets in terms of
      the root-mean-square error (RMSE), target registration error (TRE), success rate,
      and processing time. The RMSE, TRE, and the success rate of the HPS were better
      than those of the other optimization algorithms, and the processing time was
      similar to that of Powell's algorithm alone.

PMID- 23138930
TI  - Sol-gel-derived bioactive glass containing SiO2-MgO-CaO-P2O5 as an antibacterial
      scaffold.
AB  - Bioactive glass (BG) composites with a base of SiO2-Na2O-CaO-P2O5 are
      biocompatible biomaterials. The assessment of their abilities for medical
      applications has interested researchers. We produced a BG-containing SiO2-MgO-CaO
      P2O5 by the sol-gel method. To determine the antibacterial effects, we analyzed
      the minimal inhibitory concentration (MIC) and minimal bactericidal concentration
      (MBC) properties of this product on three microorganisms, Staphylococcus aureus,
      Escherichia coli and Pseudomonas aeruginosa, known causative agents for biofilm
      formation on implant surfaces. In addition, we performed the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay to study the
      cytotoxic effects of our composite on animal cells. Our results demonstrated that
      our BG product inhibited the growth of bacteria in a concentration-dependent
      manner without any cytotoxic effects. Therefore, our BG product can be utilized
      as an appropriate implant for treating bone and tooth defects.

PMID- 23138931
TI  - meso-Thiaporphyrinoids revisited: missing of sulfur by small metals.
AB  - Facile synthesis of meso-aryl-substituted 5,15-dithiaporphyrins and 10
      thiacorroles has been achieved by sulfidation of alpha,alpha'-dichlorodipyrrin
      metal complexes with sodium sulfide in DMF. Thiacorrole metal complexes exhibit
      distinct aromaticity due to 18 pi-conjugation including the lone pair on sulfur,
      whereas dithiaporphyrins are nonaromatic judging from (1)H NMR spectra, X-ray
      analysis, and absorption spectra. We have found that Ni(II) and Al(III)
      dithiaporphyrin complexes undergo smooth thermal sulfur extrusion reaction to
      give the corresponding thiacorrole complexes, whereas free base, Zn(II), Pd(II),
      and Pt(II) dithiaporphyrin complexes did not exhibit the similar reactivity. The
      DFT calculations have elucidated a reaction pathway involving an episulfide
      intermediate, which can explain the markedly different reactivity among
      dithiaporphyrin metal complexes.

PMID- 23138932
TI  - Spiritual well-being and quality of life in Iranian women with breast cancer
      undergoing radiation therapy.
AB  - PURPOSE: Psychological distress and morbidity are common consequences of
      diagnosis and treatment of breast cancer and associated with poor quality of life
      (QOL). Spiritual well-being is an important aspect of QOL, but little is known
      about the spiritual well-being and its relationship with QOL in patients of
      different cultures such as Iranian Muslim patients. The aim of this study was to
      investigate the association of QOL and spirituality among patients with breast
      cancer undergoing radiation therapy. METHODS: This was a cross-sectional study
      which was conducted in the Breast Cancer Research Center of St. S. Al-Shohada
      Hospital, Isfahan, Iran. Spiritual well-being was measured using the Functional
      Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-Sp12).
      The European Organisation for Research and Treatment of Cancer Quality of Life
      (EORTC QLQ-C30) and its supplementary breast cancer questionnaire (QLQ-BR23) were
      used to assess the quality of life of patients. Descriptive analysis, Pearson's
      correlation, and multiple regression analysis were performed for statistical
      assessment. RESULTS: In all, 68 patients fulfilled the study's inclusion criteria
      and were interviewed. The mean global QOL was 41.42 (SD = 18.02), and the mean
      spiritual well-being was 28.41 (SD = 6.95). There was a significant positive
      correlation between general QOL and total spiritual well-being scores. Also,
      spiritual well-being, social functioning, pain, and arm symptoms were significant
      predictors of global QOL. DISCUSSION: The results of this study provide evidence
      that breast cancer survivors in Iran experience a poor quality of life across a
      broad spectrum of health domains, particularly social, emotional, and spiritual,
      indicating that psychosocial-spiritual support should be considered in caring for
      patients with breast cancer.

PMID- 23138933
TI  - Human MCS5A1 candidate breast cancer susceptibility gene FBXO10 is induced by
      cellular stress and correlated with lens epithelium-derived growth factor
      (LEDGF).
AB  - Genetic variation and candidate genes associated with breast cancer
      susceptibility have been identified. Identifying molecular interactions between
      associated genetic variation and cellular proteins may help to better understand
      environmental risk. Human MCS5A1 breast cancer susceptibility associated SNP
      rs7042509 is located in F-box protein 10 (FBXO10). An orthologous Rattus
      norvegicus DNA-sequence that contains SNV ss262858675 is located in rat Mcs5a1,
      which is part of a mammary carcinoma susceptibility locus controlling tumor
      development in a non-mammary cell-autonomous manner via an immune cell-mediated
      mechanism. Higher Fbxo10 expression in T cells is associated with Mcs5a increased
      susceptibility alleles. A common DNA-protein complex bound human and rat
      sequences containing MCS5A1/Mcs5a1 rs7042509/ss262858675 in electrophoretic
      mobility shift assays (EMSAs). Lens epithelium-derived growth factor (LEDGF), a
      stress-response protein, was identified as a candidate to bind both human and rat
      sequences using DNA-pulldown and mass spectrometry. LEDGF binding was confirmed
      by LEDGF-antibody EMSA and chromatin immunoprecipitation (ChIP). Ectopic
      expression of LEDGF/p75 increased luciferase activities of co-transfected
      reporters containing both human and rat orthologs. Over-expressed LEDGF/p75
      increased endogenous FBXO10 mRNA levels in Jurkat cells, a human T-cell line,
      implying LEDGF may be involved in increasing FBXO10 transcript levels. Oxidative
      and thermal stress of Jurkat cells increased FBXO10 and LEDGF expression, further
      supporting a hypothesis that LEDGF binds to a regulatory region of FBXO10 and
      increases expression during conditions favoring carcinogenesis. We conclude that
      FBXO10, a candidate breast cancer susceptibility associated gene, is induced by
      cellular stress and LEDGF may play a role in expression of this gene.

PMID- 23138934
TI  - Involvement of peripheral cannabinoid and opioid receptors in beta-caryophyllene
      induced antinociception.
AB  - BACKGROUND: beta-caryophyllene (BCP) is a common constitute of the essential oils
      of numerous spice, food plants and major component in Cannabis. The present study
      investigated the contribution of peripheral cannabinoid (CB) and opioid systems
      in the antinociception produced by intraplantar (i.pl.) injection of BCP. The
      interaction between peripheral BCP and morphine was also examined. METHODS: The
      antinociceptive effect of i.pl. BCP was assayed by the capsaicin tests in mice.
      Antagonists for CB and opioid receptors, and antisera against beta-endorphin were
      injected peripherally prior to i.pl. injection of BCP. Morphine in combination
      with BCP was injected subcutaneously or intrathecally. RESULTS: The i.pl.
      injection of BCP dose-dependently attenuated capsaicin-induced nociceptive
      response. The antinociceptive effect produced by BCP was prevented by
      pretreatment with AM630, a selective CB2 receptor antagonist, but not by AM251, a
      selective CB1 receptor antagonist. Pretreatment with naloxone, an opioid receptor
      antagonist, and beta-funaltrexamine, a selective MU-opioid receptor antagonist,
      reversed the antinociceptive effect of BCP. Pretreatment with naloxone
      methiodide, a peripherally acting antagonist for opioid receptors and antisera
      against beta-endorphin, resulted in a significant antagonizing effect on BCP
      induced antinociception. Morphine-induced antinociception was increased by a low
      dose of BCP. The increased effect of morphine in combination with BCP was
      antagonized significantly by pretreatment with naloxone. CONCLUSIONS: The present
      results demonstrate that antinociception produced by i.pl. BCP is mediated by
      activation of CB2 receptors, which stimulates the local release from
      keratinocytes of the endogenous opioid beta-endorphin. The combined injection of
      morphine and BCP may be an alternative in treating chemogenic pain.

PMID- 23138935
TI  - Anthropometrical differences between suicide and other non-natural death
      circumstances: an autopsy study.
AB  - BACKGROUND: In international epidemiological studies, associations between
      suicides and body height, or body mass index (BMI) were found. Because of the
      recently growing number of suicides in Germany, a closer look on different
      anthropometric measures of suicide victims autopsied at the Institute of Forensic
      Medicine of the Goethe-University in Frankfurt/Main, Germany, was taken. METHOD:
      A retrospective analysis of 1,271 non-natural death cases autopsied between 2006
      and 2010 was performed. A total of 566 other than suicide (control group) and 245
      suicide cases (study group) with a given body height and weight aged between 18
      and 96 years were examined. RESULTS: Body mass indices of the 18-59-year-old male
      and 60-79-year-old female suicide victims were significantly lower. Old-aged
      women who committed suicide exhibited beside a significant lower body mass a
      significantly slender body shape measured as smaller pelvic circumference, waist
      circumference, and waist-to-tallness ratio. Self-poisoning was by far the leading
      suicide method in both genders. The victims of the suicide method hanging were
      the youngest on average, and this method was most common in the male underweight
      and female lightly normal weight BMI categories, whereas old, overweight, and
      obese men killed themselves predominantly with firearms. CONCLUSION: The analysis
      showed that body measures of suicide cases in comparison to other non-natural
      death circumstance cases differ. For criminal procedural reasons, all suicide
      cases should be autopsied. But high autopsy rates are also needed for scientific
      research and to ensure a high level of patient safety.

PMID- 23138936
TI  - Do domestic dogs interpret pointing as a command?
AB  - Domestic dogs comprehend human gestural communication flexibly, particularly the
      pointing gesture. Here, we examine whether dogs interpret pointing informatively,
      that is, as simply providing information, or rather as a command, for example,
      ordering them to move to a particular location. In the first study a human
      pointed toward an empty cup. In one manipulation, the dog either knew or did not
      know that the designated cup was empty (and that the other cup actually contained
      the food). In another manipulation, the human (as authority) either did or did
      not remain in the room after pointing. Dogs ignored the human's gesture if they
      had better information, irrespective of the authority's presence. In the second
      study, we varied the level of authority of the person pointing. Sometimes this
      person was an adult, and sometimes a young child. Dogs followed children's
      pointing just as frequently as they followed adults' pointing (and ignored the
      dishonest pointing of both), suggesting that the level of authority did not
      affect their behavior. Taken together these studies suggest that dogs do not see
      pointing as an imperative command ordering them to a particular location. It is
      still not totally clear, however, if they interpret it as informative or in some
      other way.

PMID- 23138938
TI  - Acoustofluidics 21: ultrasound-enhanced immunoassays and particle sensors.
AB  - In part 21 of the tutorial series "Acoustofluidics--exploiting ultrasonic
      standing wave forces and acoustic streaming in microfluidic systems for cell and
      particle manipulation", we review applications of ultrasonic standing waves used
      for enhancing immunoassays and particle sensors. The paper covers ultrasonic
      enhancement of bead-based immuno-agglutination assays, bead-based immuno
      fluorescence assays, vibrational spectroscopy sensors and cell deposition on a
      sensor surface.

PMID- 23138937
TI  - Shear stress during early embryonic stem cell differentiation promotes
      hematopoietic and endothelial phenotypes.
AB  - Pluripotent embryonic stem cells (ESCs) are a potential source for cell-based
      tissue engineering and regenerative medicine applications, but their translation
      into clinical use will require efficient and robust methods for promoting
      differentiation. Fluid shear stress, which can be readily incorporated into
      scalable bioreactors, may be one solution for promoting endothelial and
      hematopoietic phenotypes from ESCs. Here we applied laminar shear stress to
      differentiating ESCs using a 2D adherent parallel plate configuration to
      systematically investigate the effects of several mechanical parameters.
      Treatment similarly promoted endothelial and hematopoietic differentiation for
      shear stress magnitudes ranging from 1.5 to 15 dyne/cm(2) and for cells seeded on
      collagen-, fibronectin- or laminin-coated surfaces. Extension of the treatment
      duration consistently induced an endothelial response, but application at later
      stages of differentiation was less effective at promoting hematopoietic
      phenotypes. Furthermore, inhibition of the FLK1 protein (a VEGF receptor)
      neutralized the effects of shear stress, implicating the membrane protein as a
      critical mediator of both endothelial and hematopoietic differentiation by
      applied shear. Using a systematic approach, studies such as these help elucidate
      the mechanisms involved in force-mediated stem cell differentiation and inform
      scalable bioprocesses for cellular therapies.

PMID- 23138939
TI  - gamma-tocotrienol enhances the chemosensitivity of human oral cancer cells to
      docetaxel through the downregulation of the expression of NF-kappaB-regulated
      anti-apoptotic gene products.
AB  - Taxanes, including docetaxel, are widely used for the treatment of squamous cell
      carcinoma of the head and neck. However, the gastrointestinal toxicity of
      docetaxel has limited its high-dose clinical use. In this study, we examined the
      synergistic anticancer effects of combined low-dose docetaxel and gamma
      tocotrienol treatment on human oral cancer (B88) cells. We treated B88 cells with
      docetaxel and gamma-tocotrienol at concentrations of 0.5 nM and 50 uM,
      respectively. When cells were treated with either agent alone at a low dose, no
      significant cytotoxic effect was observed. However, the simultaneous treatment of
      cells with both agents almost completely suppressed cell growth. Whereas
      docetaxel stimulated the expression of nuclear factor-kappaB (NF-kappaB) p65
      protein in B88 cells, gamma-tocotrienol slightly inhibited the expression of
      constitutive nuclear p65 protein. Of note, the combined treatment with both
      agents inhibited docetaxel-induced nuclear p65 protein expression.
      Electrophoretic mobility shift assay (EMSA) revealed that the simultaneous
      treatment with these agents suppressed the NF-kappaB DNA binding activity in B88
      cells. In addition, gamma-tocotrienol downregulated the docetaxel-induced
      expression of NF-kappaB-regulated gene products associated with the inhibition of
      apoptosis. Furthermore, the activation of initiator caspases, caspases-8 and -9,
      and the effector caspase, caspase-3, was detected following treatment with both
      agents. Finally, apoptosis was also clearly observed as demonstrated by the
      cleavage of poly(ADP-ribose) polymerase (PARP) and nuclear fragmentation through
      the activation of caspase-3 by combined treatment with docetaxel and gamma
      tocotrienol. These findings suggest that the combination treatment with these
      agents may provide enhanced therapeutic response in oral cancer patients, while
      avoiding the toxicity associated with high-dose beta-tubulin stabilization
      monotherapy.

PMID- 23138941
TI  - Studying recombination in mouse oocytes.
AB  - Meiosis is the specialized cell division in sexually reproducing organisms in
      which haploid gametes are produced. Meiotic prophase I is the defining stage of
      meiosis, when pairing and synapsis occur between homologous chromosomes,
      concurrent with reciprocal recombination (or crossing over) events that arise
      between them. Any disruption of these events during prophase I can lead to
      improper segregation of homologous chromosomes which can cause severe birth
      defects in the resulting progeny, and this occurs with alarming frequency in
      human oocytes. Thus, while the pathways that regulate these events in prophase I
      are highly conserved in both males and females, the stringency with which these
      events are monitored and/or controlled appears to be dramatically lower in
      females. These observations underscore the need to examine and compare meiotic
      mechanisms across the sexes. However, the study of female meiosis is impeded by
      the early start of meiosis during fetal development and the very limited amount
      of ovarian tissue available for meiotic analyses. Here we describe three
      different techniques which are useful for meiotic prophase I analysis in
      mouse/human oocytes, ranging from early prophase I events through until the
      resolution of crossing over at the first and second meiotic divisions.

PMID- 23138940
TI  - Growth kinetics of CD133-positive prostate cancer cells.
AB  - BACKGROUND: In the adult human prostate CD133 expression is thought to mark rare
      prostate epithelial stem cells and malignant tumor stem/initiating cells. Such
      putative stem cell populations are thought to proliferate slowly, but possess
      unlimited proliferative potential. Based on this, we hypothesized that CD133(pos)
      prostate cancer cells proliferate slower than CD133(neg) cells. METHODS: Human
      prostate cancer cell lines were analyzed for CD133 expression and DNA content
      using flow cytometry. Rates of cell division and DNA synthesis were determined
      using CFSE cell tracing and BrdU uptake, respectively. Changes in cell cycle
      distribution and the percentage of CD133(pos) cells were assayed under conditions
      of different cell density and AR-pathway modulation. Lastly, we over-expressed
      lentiviral CD133 to measure whether CD133 regulates the cell cycle. RESULTS: The
      cell cycle distribution differs between CD133(pos) and CD133(neg) cells in all
      three human prostate cancer cell lines studied. CD133(pos) cells have a greater
      proportion of cells in G2 and proliferate faster than CD133(neg) cells. High cell
      density increases the percentage of CD133(pos) cells without changing CD133(pos)
      cell cycle progression. Treatment with the AR agonist R1881, or the anti-androgen
      MDV3100, significantly changed the percentage and proliferation of CD133(pos)
      cells. Finally, ectopic over-expression of CD133 had no effect on cell cycle
      progression. CONCLUSIONS: Contrary to our hypothesis, we demonstrate that
      CD133(pos) cells proliferate faster than CD133(neg) cells. This association of
      CD133 expression with increased cell proliferation is not directly mediated by
      CD133, suggesting that surface CD133 is a downstream target gene of an undefined
      pathway controlling cell proliferation.

PMID- 23138942
TI  - Analysis of recombinants in female mouse meiosis.
AB  - During meiosis, homologous chromosomes (homologs) undergo recombinational
      interactions, resulting in the formation of crossovers (COs) or noncrossovers
      (NCOs). Both COs and NCOs are initiated by the same event: programmed double
      strand DNA breaks (DSBs), which occur preferentially at hotspots throughout the
      genome. COs contribute to the genetic diversity of gametes and are needed to
      promote proper meiotic chromosome segregation. Accordingly, their formation is
      tightly controlled. In the mouse, the sites of preferred CO formation differ
      between male and female chromosomes, both on a regional level and on the level of
      individual hotspots. Sperm typing using (half-sided) allele-specific PCR has
      proven a powerful technique to characterize COs and all detectable NCOs at
      hotspots on male human and mouse chromosomes. In contrast, very little is known
      about the properties of hotspots in female meiosis. This chapter describes an
      adaptation of sperm typing to analyze recombinants in a hotspot, using DNA
      isolated from an ovary cell suspension enriched for oocytes.

PMID- 23138943
TI  - Studying meiosis-specific cohesins in mouse embryonic oocytes.
AB  - Distinct meiotic cohesin complexes play fundamental roles in various meiosis
      specific chromosomal events in spatiotemporally different manners during
      mammalian meiotic prophase. Immunostaining is one of the essential methods to
      study meiotic cohesin dynamics. For the study of cohesins in the meiotic prophase
      of oocytes, ovaries should be taken from the embryos during a very limited period
      before birth. Here we focus on some technical tips concerning the preparation of
      oocyte chromosome spreads for immunostaining. Further, we describe a method for
      chromosome fluorescence in situ hybridization (FISH) against immunostained
      oocytes.

PMID- 23138944
TI  - Immunohistochemical approaches to the study of human fetal ovarian development.
AB  - The development of primordial germ cells into oocytes within primordial follicles
      involves a complex sequence of proliferation, developmental commitment, entry and
      arrest in meiosis, and association with surrounding somatic cells. These
      processes occur over the first few months of development in the human, with
      multiple stages of development present at any one time point.
      Immunohistochemistry has been hugely instructive in identifying the various key
      stages in ovarian development, by allowing simultaneous visualization of
      different stages of germ cell development, and their spatial arrangement. These
      studies allow comparison with other species and have identified key differences
      between human and murine ovarian development as well as giving a basis for
      functional studies. In this chapter we describe the main methodologies used in
      immunohistochemistry, using both chromogen and fluorescence approaches, and both
      single and double antigen detection.

PMID- 23138945
TI  - Protein kinase assays for measuring MPF and MAPK activities in mouse and rat
      oocytes and early embryos.
AB  - Protein phosphorylation plays a pivotal role in cell cycle regulation. MPF (M
      phase Promoting Factor) and MAPK (Mitogen-activated protein kinase) are two major
      kinases driving oocyte maturation and early embryonic divisions. Their activities
      can be measured experimentally with kinase assays that use specific exogenous
      substrates. The activities of MPF and MAPK are measured using histone H1 kinase
      and MBP (Myelin Basic Protein) kinase assays, respectively. Here, we describe
      detailed procedures for measuring these two activities in mouse and rat oocytes
      and in early mouse embryos. The assays we describe can be performed using very
      small amounts of biological material and produce clearly discernible measurements
      of histone H1 and MBP kinase activities.

PMID- 23138946
TI  - Time-lapse epifluorescence imaging of expressed cRNA to cyclin B1 for studying
      meiosis I in mouse oocytes.
AB  - The first meiotic division of mammalian oocytes physiologically occurs in the
      ovary in the hours preceding ovulation. Fortunately, oocytes removed from their
      follicular environment will readily undergo this process in culture. Their large
      size, optical transparency, and efficiency in translating exogenous cRNA make
      mouse oocytes very amenable to study this process in detail using fluorescence
      imaging-based techniques. Here we describe the process of microinjecting cRNA to
      proteins of interest that have been coupled to a fluorescent protein using cyclin
      B1 as an example.

PMID- 23138947
TI  - Using FRET to study RanGTP gradients in live mouse oocytes.
AB  - Oocytes are extremely large cells that have to coordinate accurate chromosome
      segregation, asymmetric cytoplasm partitioning together with their own
      development as fertilizable gametes. For this, they undergo both global (cell
      cycle progression related) and local changes. It is therefore essential to be
      able to monitor local changes as they take place in live maturing oocytes. We
      describe here a method to follow RanGTP gradients using FRET technology in vivo.

PMID- 23138948
TI  - Making cRNA for microinjection and expression of fluorescently tagged proteins
      for live-cell imaging in oocytes.
AB  - Fluorescently tagged proteins have become a crucial weapon in the armory of a
      successful cell biology laboratory. This chapter describes how to produce cRNA
      coding for a fluorescently tagged protein of choice, such that it is suitable for
      microinjection and subsequent expression studies in live oocytes.

PMID- 23138949
TI  - RNAi-based methods for gene silencing in mouse oocytes.
AB  - RNA interference (RNAi) is an evolutionary conserved gene-silencing pathway that
      can be efficiently utilized as a tool to study gene function. RNAi is initiated
      by long double-stranded RNAs (dsRNAs), which are processed into small duplexes
      called small-interfering RNAs (siRNAs). In turn, these duplexes target mRNAs for
      degradation in a sequence-specific manner. Mouse oocytes, unlike most mammalian
      cell types, lack an interferon response to long dsRNA. Moreover, they are a rare
      example of a mammalian cell type with a robust endogenous RNAi pathway. For these
      reasons microinjection of either long dsRNAs or siRNAs results in efficient,
      sequence-specific gene silencing. Here, we describe a protocol for preparation
      and microinjection of long dsRNA into mouse oocytes.

PMID- 23138950
TI  - Micro-injection of Morpholino oligonucleotides for depleting Securin in mouse
      oocytes.
AB  - Gene silencing techniques have brought new insights into mammalian oocyte and
      embryo development. More specifically, the use of Morpholino oligonucleotides
      which sterically inhibit translation from target mRNAs thereby compromising gene
      function, allowed the identification of important oocyte regulators and
      especially factors involved in meiotic cell cycle control. Here we describe the
      method of application of Morpholino oligonucleotides in mouse oocyte research.

PMID- 23138951
TI  - Measuring transport and accumulation of radiolabeled substrates in oocytes and
      embryos.
AB  - Radiolabeled compounds that are substrates for transmembrane transporters can be
      used to study transport and metabolism in mammalian oocytes and preimplantation
      embryos. Because even very small amounts of radioisotopes can be detected, these
      techniques are feasible to use with only a few oocytes or embryos, even down to
      the level of single oocytes or embryos. Here, we describe the methods for
      determining the transport and accumulation of radiolabeled compounds into oocytes
      and preimplantation embryos and the determination of the rate of saturable
      transport via specific transporters in the plasma membrane.

PMID- 23138952
TI  - Immunofluorescence staining of spindles, chromosomes, and kinetochores in human
      oocytes.
AB  - Understanding how human oocytes execute chromosome segregation is of paramount
      importance as errors in this process account for the overwhelming majority of
      human aneuploidies and increase exponentially with advancing female age. The
      spindle is the cellular apparatus responsible for separating chromosomes at
      anaphase. For accurate chromosome segregation, spindle microtubules must
      establish appropriately configured attachments to chromosomes via kinetochores.
      With regard to understanding the mechanistic basis for human aneuploidies
      therefore, it will be important to explore the molecular underpinnings of spindle
      structure and the interaction of its microtubules with chromosomes in human
      oocytes. Here we describe a technique for simultaneously immunolabelling
      chromosomes, spindle microtubules and kinetochores in human oocytes.

PMID- 23138953
TI  - Studying the roles of Aurora-C kinase during meiosis in mouse oocytes.
AB  - We previously isolated Aurora-C (Aurkc/Aie1) in a screen for kinases expressed in
      mouse sperm and eggs. Aurora-C kinase was reported to be a chromosomal passenger
      protein that plays critical roles in chromosome alignment, segregation,
      kinetochore-microtubule attachment, and cytokinesis in female mouse meiosis. This
      chapter describes experimental approaches for examining the subcellular
      localization and function of Aurora-C kinase during female mouse meiosis,
      presenting detailed methods for introducing exogenous Aurora-C wild-type and
      kinase-dead mutant mRNAs into mouse oocytes by cytosolic microinjection, and
      preparing whole-mount meiotic oocytes and chromosome spreads for confocal
      immunofluorescence microscopy.

PMID- 23138954
TI  - Chromosome spreads with centromere staining in mouse oocytes.
AB  - This chapter describes a technique for performing chromosome spreads from mouse
      oocytes. It is based on a previously described protocol (Hodges and Hunt,
      Chromosoma 111: 165-169, 2002), which we have modified. Chromosomes are stained
      with either Propidium Iodide or Hoechst. This spreading technique allows for
      simultaneous immunostaining of proteins associated with chromosomes. It is very
      useful to stain spreads with CREST serum which labels kinetochores, to be able to
      distinguish bivalents (chromosome pairs), dyads or univalents (paired sister
      chromatids), and single sister chromatids without ambiguity.

PMID- 23138955
TI  - Preparation of mammalian oocytes for transmission electron microscopy.
AB  - The visualization of subcellular organelles and structures is a valuable tool for
      understanding cellular changes that occur in oocytes and early embryos as a
      result of genetic alterations, incubation conditions, drug treatments, and many
      other manipulations. Preparing oocytes for transmission electron microscopic
      analysis can be challenging as these cells cannot be visualized without a
      microscope and they are more susceptible to mechanical disruption during
      manipulation. Here we describe methods for immobilizing oocytes on either a solid
      surface or within a matrix and then document our embedding techniques which work
      well for preserving the ultrastructure of the mouse oocyte.

PMID- 23138956
TI  - Measuring Ca2+ oscillations in mammalian eggs.
AB  - At fertilization mammalian eggs are activated by a prolonged series of
      oscillations in the intracellular free Ca(2+) concentration. These oscillations
      can be monitored with any number of Ca(2+)-sensitive fluorescent dyes. The
      oscillations last for several hours at fertilization and so there are some
      considerations with mammalian eggs that make them distinct from somatic cells
      that are commonly used in Ca(2+) imaging experiments. I describe the use of two
      particular dyes that can be loaded into mouse eggs and that give the most
      valuable results. The first one is PE3 which can be loaded by incubation with the
      AM form of the dye which is membrane permeable. The other is rhod dextran which
      requires microinjection. Either one of these dyes offers advantages over the more
      commonly used fura2. I describe the way that the fluorescence from dye-loaded
      eggs is measured with a conventional epifluorescence microscope and a CCD camera.

PMID- 23138957
TI  - Counting chromosomes in intact eggs.
AB  - Chromosomal spreads are an established method to assess ploidy in different cell
      types. However, many traditional chromosome-spreading techniques require
      dissolution of the cell and can only be used to assess hyperploidy because of
      potential chromosome loss inherent in the procedure. Here we describe a method to
      evaluate chromosome numbers in intact eggs so that both hyperploidy and
      hypoploidy can be accurately detected.

PMID- 23138958
TI  - Free-hand bisection of mouse oocytes and embryos.
AB  - Mouse oocytes and zygotes are semitransparent and large cells approximately 80
      MUm in diameter. Bisection is one of the easiest ways for performing
      micromanipulations on such cells. It allows living sister halves or smaller
      fragments to be obtained, which can be cultured and observed for long periods of
      time. Bisection can be used for different kinds of experiments such as analysis
      of nucleo-cytoplasmic interactions, the relationship between different cellular
      structures or between different parts of embryos, eventually for analyzing the
      developmental potential of embryonic fragments. Oocyte or embryo halves can be
      examined by immunostaining, by measuring different cellular functions and by
      Western blot and genetic analysis (e.g., RT-PCR). Here we describe a detailed
      protocol for the free-hand bisection of mouse zona pellucida-free oocytes and
      embryos on an agar layer using a glass needle.

PMID- 23138959
TI  - Microarray-CGH for the assessment of aneuploidy in human polar bodies and
      oocytes.
AB  - The cytogenetic analysis of single cells, such as oocytes and polar bodies, is
      extremely challenging. The main problem is low probability of obtaining a
      metaphase preparation in which all of the chromosomes are sufficiently well
      spread to permit accurate analysis (no overlapping chromosomes, no chromosomes
      lost). As a result, a high proportion of the oocytes subjected to cytogenetic
      analysis are not suitable for traditional chromosome banding studies or for
      molecular cytogenetic methods such as spectral karyotyping (SKY) or multiplex
      fluorescence in situ hybridization (M-FISH). Fortunately, recent innovations in
      whole genome amplification and microarray technologies have provided a means to
      analyze the copy number of every chromosome in single cells with high accuracy.
      Here we describe the use of such methods for the investigation of chromosome and
      chromatid abnormalities in human oocytes and polar bodies.

PMID- 23138960
TI  - Nuclear transfer in the mouse oocyte.
AB  - The nuclear transfer (NT) technique in the mouse has enabled us to generate
      cloned mice and to establish NT embryonic stem (ntES) cells. Direct nuclear
      injection into mouse oocytes with a piezo impact drive unit can aid in the bypass
      of several steps of the original cell fusion procedure. It is important to note
      that only the NT approach can reveal dynamic and global modifications in the
      epigenome without using genetic modification as well as generating live animals
      from single cells. Thus, these techniques could also be applied to the
      preservation of genetic material from any mouse strain instead of preserving
      embryos or gametes. Moreover, with this technique, we can use not only living
      cells but also the nuclei of dead cells from frozen mouse carcasses for NT. This
      chapter describes our most recent protocols of NT into the mouse oocyte for
      cloning mice and for the establishment of ntES cells from cloned embryos.

PMID- 23138962
TI  - Poly(vinylidene fluoride)/nickel nanocomposites from semicrystalline block
      copolymer precursors.
AB  - The fabrication of nanoporous poly(vinylidene fluoride) (PVDF) and PVDF/nickel
      nanocomposites from semicrystalline block copolymer precursors is reported.
      Polystyrene-block-poly(vinylidene fluoride)-block-polystyrene (PS-b-PVDF-b-PS) is
      prepared through functional benzoyl peroxide initiated polymerization of VDF,
      followed by atom transfer radical polymerization (ATRP) of styrene. The
      crystallization of PVDF plays a dominant role in the formation of the block
      copolymer structure, resulting in a spherulitic superstructure with an internal
      crystalline-amorphous lamellar nanostructure. The block copolymer promotes the
      formation of the ferroelectric beta-polymorph of PVDF. Selective etching of the
      amorphous regions with nitric acid leads to nanoporous PVDF, which functions as a
      template for the generation of PVDF/Ni nanocomposites. The lamellar nanostructure
      and the beta-crystalline phase are conserved during the etching procedure and
      electroless nickel deposition.

PMID- 23138961
TI  - Randomized controlled trial of contingency management for stimulant use in
      community mental health patients with serious mental illness.
AB  - OBJECTIVE: The primary objective of this study was to determine whether
      contingency management was associated with increased abstinence from stimulant
      drug use in stimulant-dependent patients with serious mental illness treated in a
      community mental health center. Secondary objectives were to determine whether
      contingency management was associated with reductions in use of other substances,
      psychiatric symptoms, HIV risk behavior, and inpatient service utilization.
      METHOD: A randomized controlled design was used to compare outcomes of 176
      outpatients with serious mental illness and stimulant dependence. Participants
      were randomly assigned to receive 3 months of contingency management for
      stimulant abstinence plus treatment as usual or treatment as usual with
      reinforcement for study participation only. Urine drug tests and self report,
      clinician-report, and service utilization outcomes were assessed during the 3
      month treatment period and the 3-month follow-up period. RESULTS: Although
      participants in the contingency management condition were significantly less
      likely to complete the treatment period than those assigned to the control
      condition (42% compared with 65%), they were 2.4 times (95% CI=1.9-3.0)more
      likely to submit a stimulant-negative urine test during treatment. Compared with
      participants in the control condition,they had significantly lower levels of
      alcohol use, injection drug use, and psychiatric symptoms and were one-fifth as
      likely as those assigned to the control condition to be admitted for psychiatric
      hospitalization during treatment. They also reported significantly fewer days of
      stimulant drug use during the 3-month follow-up. CONCLUSIONS: When added to
      treatment as usual, contingency management is associated with large reductions in
      stimulant,injection drug, and alcohol use.Reductions in psychiatric symptoms and
      hospitalizations are important secondary benefits.

PMID- 23138963
TI  - In vitro osteoblast response to ferritic stainless steel fiber networks for
      magneto-active layers on implants.
AB  - The use of a porous coating on prosthetic components to encourage bone ingrowth
      is an important way of improving uncemented implant fixation. Enhanced fixation
      may be achieved by the use of porous magneto-active layers on the surface of
      prosthetic implants, which would deform elastically on application of a magnetic
      field, generating internal stresses within the in-growing bone. This approach
      requires a ferromagnetic material able to support osteoblast attachment,
      proliferation, differentiation, and mineralization. In this study, the human
      osteoblast responses to ferromagnetic 444 stainless steel networks were
      considered alongside those to nonmagnetic 316L (medical grade) stainless steel
      networks. While both networks had similar porosities, 444 networks were made from
      coarser fibers, resulting in larger inter-fiber spaces. The networks were
      analyzed for cell morphology, distribution, proliferation, and differentiation,
      extracellular matrix production and the formation of mineralized nodules. Cell
      culture was performed in both the presence of osteogenic supplements, to
      encourage cell differentiation, and in their absence. It was found that fiber
      size affected osteoblast morphology, cytoskeleton organization and proliferation
      at the early stages of culture. The larger inter-fiber spaces in the 444 networks
      resulted in better spatial distribution of the extracellular matrix. The addition
      of osteogenic supplements enhanced cell differentiation and reduced cell
      proliferation thereby preventing the differences in proliferation observed in the
      absence of osteogenic supplements. The results demonstrated that 444 networks
      elicited favorable responses from human osteoblasts, and thus show potential for
      use as magnetically active porous coatings for advanced bone implant
      applications.

PMID- 23138965
TI  - Synthesis, structure, and reactivity of a nickel dihydrogen complex.
AB  - Hydrogen activation by nickel: A tBuPCP pincer ligand facilitates formation of
      cationic Ni(II)  dihydrogen and terminal dinitrogen complexes. The compounds have
      been characterized by X-ray crystallography and NMR spectroscopy. Addition of
      base promotes heterolytic cleavage of H(2)  to form the corresponding neutral
      hydride complex.

PMID- 23138964
TI  - Inflammation-based prognostic score is a useful predictor of postoperative
      outcome in patients with extrahepatic cholangiocarcinoma.
AB  - BACKGROUND/PURPOSE: Recent studies have revealed that the Glasgow prognostic
      score (GPS), an inflammation-based prognostic score, is useful for predicting
      outcome in a variety of cancers. This study sought to investigate the
      significance of GPS for prognostication of patients who underwent surgery with
      extrahepatic cholangiocarcinoma. METHODS: We retrospectively analyzed a total of
      62 patients who underwent resection for extrahepatic cholangiocarcinoma. We
      calculated the GPS as follows: patients with both an elevated C-reactive protein
      (>10 mg/L) and hypoalbuminemia (<35 g/L) were allocated a score of 2; patients
      with one or none of these abnormalities were allocated a s ore of 1 or 0,
      respectively. Prognostic significance was analyzed by the log-rank test and a Cox
      proportional hazards model. RESULTS: Overall survival rate was 25.5 % at 5 years
      for all 62 patients. Venous invasion (p = 0.01), pathological primary tumor
      category (p = 0.013), lymph node metastasis category (p < 0.001), TNM stage (p <
      0.001), and GPS (p = 0.008) were significantly associated with survival by
      univariate analysis. A Cox model demonstrated that increased GPS was an
      independent predictive factor with poor prognosis. CONCLUSIONS: The preoperative
      GPS is a useful predictor of postoperative outcome in patients with extrahepatic
      cholangiocarcinoma.

PMID- 23138966
TI  - Return to sport following anterior cruciate ligament reconstruction.
AB  - Rates of return to pre-injury sport following anterior cruciate ligament (ACL)
      reconstruction are less than might be expected from standard outcome measures and
      there appears to be a rapid decline in sporting participation after two to three
      years. There are many factors that influence whether an individual will return to
      sport following this type of surgery. They include not only surgical details and
      rehabilitation, but also social and psychological factors, as well as demographic
      characteristics. Age is of particular importance with older patients being less
      likely to resume their pre-injury sport. It is important that future research
      clearly identify the pre-injury characteristics of the study cohort when
      investigating return to sport, and also that there is consistent and precise
      terminology used to report rates of return to sporting activities. Little is
      known about how to determine when it is safe to return to sport following ACL
      reconstruction or how to predict whether an athlete will be able to successfully
      return to sport. Finally, it needs to be recognised that return to sport
      following ACL reconstruction is associated with a risk of further injury and the
      development of osteoarthritis.

PMID- 23138967
TI  - Shape of growth plate of proximal femur in children and its significance in the
      aetiology of slipped capital femoral epiphysis.
AB  - PURPOSE: The main objective of the study was to present the influence of the
      morphological shape of the proximal femoral growth plate in children as one of
      the risk factors for the incidence of slipped capital femoral epiphysis (SCFE) in
      adolescents. METHODS: This research is based on the X-ray, computed tomography
      (CT) and magnetic resonance imaging (MRI) data obtained for 100 children three to
      13 years old, all treated at the Children's Orthopaedic Clinic and Rehabilitation
      Department and Department of Radiology Medical University of Lublin between 2005
      and 2009. We took into account 83 children with healthy hip joints and 17
      children with SCFE. We also performed morphological analysis of the shape of the
      proximal femoral growth plate together with X-ray, CT and MRI examinations of the
      proximal ends of cadaver femurs for two children aged six and 13. RESULTS: In the
      final findings we present an analysis of the shape of the proximal femoral growth
      plate in children between the third and 13th years of life and consider a
      correlation between the shape of the proximal femoral growth plate and its
      influence on the incidence of SCFE in adolescents. CONCLUSIONS: The change of
      shape of the proximal femoral growth plate from pleated to more spherical is one
      of the risk factors for the incidence of SCFE in children ten years old and
      older.

PMID- 23138968
TI  - The fate of Bohler's angle in conservatively-treated displaced intra-articular
      calcaneal fractures.
AB  - PURPOSE: Although the predictive value of Bohler's angle on outcome remains
      subject of debate, the initial angle at the time of trauma still guides
      treatment. Changes in Bohler's angle during follow-up are frequently reported
      following surgical treatment of displaced intra-articular calcaneal fractures
      (DIACF). The aim of the present study was to determine the changes in Bohler's
      angle as a measure of secondary fracture displacement following conservative
      management of DIACF. METHODS: Thirty-eight patients with a total of 44 displaced
      intra-articular calcaneal fractures treated conservatively with a minimum of two
      lateral radiographs during follow-up were analysed. Bohler's angle at different
      follow-up times was measured by three observers. The change in angle was compared
      with the angle at trauma, and influence of trauma mechanism and common calcaneal
      fracture classifications were determined. RESULTS: The results showed a
      significant decline over time of the Bohler's angle in conservatively-treated
      patients of more than 11 degrees  on average at a mean follow-up of 29.2 weeks.
      This decrease was not related to gender, the initial angle, or the Essex-Lopresti
      or Sanders classification. A statistically significantly higher decrease was
      detected in high energetic trauma compared with low energetic trauma. CONCLUSION:
      The conservative treatment of displaced intra-articular calcaneal fractures is
      still a viable option, yet a significant secondary displacement in time should be
      taken into account, as reflected in a decrease of Bohler's angle of 11 degrees 
      up to one year following trauma.

PMID- 23138969
TI  - Stress fractures in elderly patients.
AB  - PURPOSE: The purpose of this study was to investigate specific risk factors,
      common fracture locations and possible sex-specific differences in elderly
      patients with stress fractures. METHODS: This analysis enrolled 105 patients (83
      women, 22 men) with stress fractures. For the analysis of possible risk factors
      related to increasing age, data from 82 patients (67 women, 15 men) aged 40 years
      and older (mean age of 57.4 +/- 11.0 years) were compared with that from a
      younger control group [23 patients (16 women, seven men), mean age 28.4 +/- 6.7
      years]. Bone mineral density (BMD) was determined using dual-energy X-ray
      absorptiometry bone densitometry (DXA) and blood samples were taken. RESULTS: A
      total of 211 stress fractures were found. Of these, 177 were found in the study
      group, of which 90.4 % were located in the lower limb. Lumbar and femoral BMD was
      significantly lower in elderly patients; however, the BMD of most patients was
      within the osteopenic or normal range. Within the study group, a total of 83.8 %
      had a vitamin D insufficiency (<30 MUg/l); 75.5 % were not engaged in regular
      physical activity more than once a week. Overweight patients within the study
      group had significantly more stress fractures compared to normal weight patients
      (2.6 +/- 1.7 vs. 1.9 +/- 1.1, p<0.05). CONCLUSIONS: A similar contribution of
      risk factors has been found for stress fractures in elderly patients and younger
      controls of the general population. Stress fracture incidence seems to be rather
      multifactorial and not based on osteoporotic changes alone. A balanced calcium
      and vitamin D metabolism seems to be of paramount importance for stress fracture
      prevention in elderly patients.

PMID- 23138971
TI  - In silico analysis of nanomaterials hazard and risk.
AB  - Because a variety of human-related activities, engineer-ed nanoparticles (ENMs)
      may be released to various environmental media and may cross environmental
      boundaries, and thus will be found in most media. Therefore, the potential
      environmental impacts of ENMs must be assessed from a multimedia perspective and
      with an integrated risk management approach that considers rapid developments and
      increasing use of new nanomaterials. Accordingly, this Account presents a
      rational process for the integration of in silico ENM toxicity and fate and
      transport analyses for environmental impact assessment. This approach requires
      knowledge of ENM toxicity and environmental exposure concentrations. Considering
      the large number of current different types of ENMs and that those numbers are
      likely to increase, there is an urgent need to accelerate the evaluation of their
      toxicity and the assessment of their potential distribution in the environment.
      Developments in high throughput screening (HTS) are now enabling the rapid
      generation of large data sets for ENM toxicity assessment. However, these
      analyses require the establishment of reliable toxicity metrics, especially when
      HTS includes data from multiple assays, cell lines, or organisms. Establishing
      toxicity metrics with HTS data requires advanced data processing techniques in
      order to clearly identify significant biological effects associated with exposure
      to ENMs. HTS data can form the basis for developing and validating in silico
      toxicity models (e.g., quantitative structure-activity relationships) and for
      generating data-driven hypotheses to aid in establishing and/or validating
      possible toxicity mechanisms. To correlate the toxicity of ENMs with their
      physicochemical properties, researchers will need to develop quantitative
      structure-activity relationships for nanomaterials (i.e., nano-SARs). However, as
      nano-SARs are applied in regulatory applications, researchers must consider their
      applicability and the acceptance level of false positive relative to false
      negative predictions and the reliability of toxicity data. To establish the
      environmental impact of ENMs identified as toxic, researchers will need to
      estimate the potential level of environmental exposure concentration of ENMs in
      the various media such as air, water, soil, and vegetation. When environmental
      monitoring data are not available, models of ENMs fate and transport (at various
      levels of complexity) serve as alternative approaches for estimating exposure
      concentrations. Risk management decisions regarding the manufacturing, use, and
      environmental regulations of ENMs would clearly benefit from both the assessment
      of potential ENMs exposure concentrations and suitable toxicity metrics. The
      decision process should consider the totality of available information:
      quantitative and qualitative data and the analysis of nanomaterials toxicity, and
      fate and transport behavior in the environment. Effective decision-making to
      address the potential impacts of nanomaterials will require considerations of the
      relevant environmental, ecological, technological, economic, and sociopolitical
      factors affecting the complete lifecycle of nanomaterials, while accounting for
      data and modeling uncertainties. Accordingly, researchers will need to establish
      standardized data management and analysis tools through nanoinformatics as a
      basis for the development of rational decision tools.

PMID- 23138970
TI  - Chronic lung allograft dysfunction after lung transplantation: the moving target.
AB  - Chronic lung allograft dysfunction is a major challenge in long-term management
      of lung transplant recipients. Both alloimmune-dependent factors (rejection) and
      alloimmune-independent factors contribute to the development of chronic lung
      allograft dysfunction. Thus, use of the term "chronic rejection" tends to be
      intentionally avoided among specialists in the field, although "chronic
      rejection" is still an acceptable lay word understood by many patients. Several
      different phenotypes have been identified in chronic lung allograft dysfunction,
      including restrictive allograft syndrome, neutrophilic reversible allograft
      dysfunction, and fibrous bronchiolitis obliterans syndrome. Restrictive allograft
      syndrome is characterized by restrictive physiology and peripheral foci of
      inflammation and fibrosis, which contrasts the obstructive physiology and
      pathological foci in small airways in conventional bronchiolitis obliterans
      syndrome. Among patients with bronchiolitis obliterans syndrome, there is a
      subpopulation that responds relatively well to azithromycin. Because these
      patients show airway neutrophilia, this subtype of chronic lung allograft
      dysfunction was named neutrophilic reversible allograft dysfunction. Conversely,
      patients with bronchiolitis obliterans syndrome unresponsive to azithromycin show
      airway fibrosis with less inflammation (fibrous bronchiolitis obliterans
      syndrome). In general, restrictive allograft syndrome shows poorer survival than
      does bronchiolitis obliterans syndrome, and early-onset bronchiolitis obliterans
      syndrome (within 2 years) shows a worse prognosis than does late-onset
      bronchiolitis obliterans syndrome. Until preventive and therapeutic options are
      refined, chronic lung allograft dysfunction will remain a major life-limiting
      factor. It has significant psychological, physical, social, and economic impacts.
      Early introduction of palliative care is another important strategy to improve
      patients' quality of life.

PMID- 23138972
TI  - Homogeneous palladium-catalyzed asymmetric hydrogenation.
AB  - The transition metal catalyzed asymmetric hydrogenation of unsaturated compounds
      arguably presents one of the most attractive methods for the synthesis of chiral
      compounds. Over the last few decades, Pd has gradually grown up as a new and
      popular metal catalyst in homogeneous asymmetric hydrogenation the same as
      traditional Ru, Rh and Ir catalysts. Much progress has been successfully achieved
      in the asymmetric reduction of imines, enamines, olefins, ketones and
      heteroarenes. It was also found that palladium catalyzed asymmetric hydrogenation
      could be used as a key step in tandem reactions to quickly synthesize chiral
      compounds. This tutorial review intends to offer an overview of recent progress
      in homogeneous palladium catalyzed asymmetric hydrogenation and should serve as
      an inspiration for further advances in this area.

PMID- 23138973
TI  - (Val(8))GLP-1-Glu-PAL: a GLP-1 agonist that improves hippocampal neurogenesis,
      glucose homeostasis, and beta-cell function in high-fat-fed mice.
AB  - This study examined the biological properties of a novel GLP-1 peptide,
      (Val(8))GLP-1-Glu-PAL, engineered with an Ala(8)->Val(8) substitution and
      additional incorporation of a C(16) fatty acid moiety at Lys(26) via a glutamic
      acid linker. GLP-1 underwent 75 % degradation by DPP-IV over 8 h, whereas
      (Val(8))GLP-1 and (Val(8))GLP-1-Glu-PAL remained intact. All GLP-1 peptides
      significantly stimulated insulin secretion at 5.6 mM (1.3- to 4.9-fold, p<0.01 to
      p<0.001) and 16.7 mM glucose (1.5- to 2.3-fold, p<0.001). At higher
      concentrations (Val(8))GLP-1-Glu-PAL was significantly more potent at stimulating
      insulin secretion (1.2- to 1.3-fold, p<0.05). In high-fat-fed mice, all GLP-1
      peptides significantly lowered plasma glucose concentrations (41-66 % decrease,
      p<0.05 to p<0.001), with (Val(8))GLP-1-Glu-PAL eliciting protracted glucose
      lowering actions (32-59 % decrease, p<0.05 to p<0.01) when administered 8 h prior
      to a glucose load. Twice-daily administration of (Val(8))GLP-1-Glu-PAL in high
      fat-fed mice for 21 days had no effect on bodyweight or food intake, but
      significantly lowered non-fasting plasma glucose (43-46 % decrease, p<0.05).
      (Val(8))GLP-1-Glu-PAL markedly decreased glycemic excursion following
      intraperitoneal glucose (32-48 % decrease, p<0.05), enhanced insulin response to
      glucose (2- to 2.3-fold, p<0.05 to p<0.01), and improved insulin sensitivity (25
      38 % decrease in plasma glucose, p<0.05). O(2) consumption, CO(2) production,
      RER, and energy expenditure were not altered by (Val(8))GLP-1-Glu-PAL therapy.
      Treatment with (Val(8))GLP-1-Glu-PAL resulted in a significant increase in BrdU
      positive cells (1.3-fold, p<0.05) in the granule cell layer of the dentate gyrus.
      These data demonstrate that (Val(8))GLP-1-Glu-PAL is a long-acting GLP-1 peptide
      that significantly improves hippocampal neurogenesis, glucose homeostasis, and
      insulin secretion in high-fat-fed mice.

PMID- 23138975
TI  - Socio-demographic and clinical profile of chronic pain with neuropathic
      characteristics in sub-Saharan African elderly.
AB  - Data on characteristics of neuropathic pain (NP) in sub-Saharan Africa are
      scarce, especially in the elderly. We conducted this study to appreciate the
      socio-demographic and clinical profile of chronic pain (CP) with neuropathic
      characteristics in sub-Saharan African elderly with musculoskeletal pain. From
      January to December 2011, we performed a cross-sectional study in all
      Rheumatology outpatients over 60 years at the Center for Gerontology and
      Geriatrics, Dakar, Senegal. In this study, we included patients who experienced
      musculoskeletal pain for 3 months or longer (CP) and with a DN4 score >= 4 (NP).
      A complete clinical examination was performed to make the diagnosis of NP
      'definite' or 'probable', and to identify the aetiologies of NP. During the study
      period, 698 outpatients were examined. There were 394 out of the 549 patients
      over 60 years who reported CP. Among them, 28 patients (7.1%) scored >=4 on the
      DN4 questionnaire. Female patients, low educational attainment, manual
      professions, non-workers and diabetes were associated with NP (p < 0.05). The
      symptoms described by patients with NP, often intricate, were lumboradiculalgia
      (n = 9), cervico-brachial neuralgia (n = 3), polyneuropathy (n = 12) and
      mononeuropathy (n = 6). The presumed aetiologies in patients with NP were:
      chronic spine diseases (n = 14), painful diabetic peripheral neuropathy (n = 8),
      Sjogren's syndrome (n = 1), tarsal tunnel syndrome in rheumatoid arthritis (n =
      1) and bone metastasis (n = 1). No aetiology was identified among three patients.
      Chronic spine diseases associated with radiculopathies and diabetic neuropathy
      are the main causes of NP, well detected by DN4 questionnaire and clinical
      examination in Senegalese sub-Saharan African elderly.

PMID- 23138974
TI  - Japanese Papilio butterflies puddle using Na+ detected by contact chemosensilla
      in the proboscis.
AB  - Many butterflies acquire nutrients from non-nectar sources such as puddles. To
      better understand how male Papilio butterflies identify suitable sites for
      puddling, we used behavioral and electrophysiological methods to examine the
      responses of Japanese Papilio butterflies to Na(+), K(+), Ca(2+), and Mg(2+).
      Based on behavioral analyses, these butterflies preferred a 10-mM Na(+) solution
      to K(+), Ca(2+), and Mg(2+) solutions of the same concentration and among a
      tested range of 1 mM to 1 M NaCl. We also measured the ion concentrations of
      solutions sampled from puddling sites in the field. Na(+) concentrations of the
      samples were up to 6 mM, slightly lower than that preferred by butterflies in the
      behavioral experiments. Butterflies that sipped the 10 mM Na(+) solution from the
      experimental trays did not continue to puddle on the ground. Additionally,
      butterflies puddled at sites where the concentrations of K(+), Ca(2+), and/or
      Mg(2+) were higher than that of Na(+). This suggests that K(+), Ca(2+), and
      Mg(2+) do not interfere with the detection of Na(+) by the Papilio butterfly.
      Using an electrophysiological method, tip recordings, receptor neurons in contact
      chemosensilla inside the proboscis evoked regularly firing impulses to 1, 10, and
      100 mM NaCl solutions but not to CaCl(2) or MgCl(2). The dose-response patterns
      to the NaCl solutions were different among the neurons, which were classified
      into three types. These results showed that Japanese Papilio butterflies puddle
      using Na(+) detected by the contact chemosensilla in the proboscis, which measure
      its concentration.

PMID- 23138976
TI  - Biomimetic injectable HUVEC-adipocytes/collagen/alginate microsphere co-cultures
      for adipose tissue engineering.
AB  - Engineering adipose tissue that has the ability to engraft and establish a
      vascular supply is a laudable goal that has broad clinical relevance,
      particularly for tissue reconstruction. In this article, we developed novel
      microtissues from surface-coated adipocyte/collagen/alginate microspheres and
      human umbilical vein endothelial cells (HUVECs) co-cultures that resembled the
      components and structure of natural adipose tissue. Firstly, collagen/alginate
      hydrogel microspheres embedded with viable adipocytes were obtained to mimic fat
      lobules. Secondly, collagen fibrils were allowed to self-assemble on the surface
      of the microspheres to mimic collagen fibrils surrounding the fat lobules in the
      natural adipose tissue and facilitate HUVEC attachment and co-cultures formation.
      Thirdly, the channels formed by the gap among the microspheres served as the room
      for in vitro prevascularization and in vivo blood vessel development. The
      endothelial cell layer outside the microspheres was a starting point of rapid
      vascular ingrowth. Adipose tissue formation was analyzed for 12 weeks at 4-week
      intervals by subcutaneous injection into the head of node mice. The vasculature
      in the regenerated tissue showed functional anastomosis with host blood vessels.
      Long-term stability of volume and weight of the injection was observed,
      indicating that the vasculature formed within the constructs benefited the
      formation, maturity, and maintenance of adipose tissue. This study provides a
      microsurgical method for adipose regeneration and construction of biomimetic
      model for drug screening studies.

PMID- 23138977
TI  - A case of midbrain infarction causing ipsilateral mydriasis, contralateral
      superior rectus palsy, and bilateral ptosis.

PMID- 23138978
TI  - Kinetic responses of beta-catenin specify the sites of Wnt control.
AB  - Despite more than 30 years of work on the Wnt signaling pathway, the basic
      mechanism of how the extracellular Wnt signal increases the intracellular
      concentration of beta-catenin is still contentious. Circumventing much of the
      detailed biochemistry, we used basic principles of chemical kinetics coupled with
      quantitative measurements to define the reactions on beta-catenin directly
      affected by the Wnt signal. We conclude that the core signal transduction
      mechanism is relatively simple, with only two regulated phosphorylation steps.
      Their partial inhibition gives rise to the full dynamics of the response and
      subsequently maintains a steady state in which the concentration of beta-catenin
      is increased.

PMID- 23138979
TI  - Robust photogeneration of H2 in water using semiconductor nanocrystals and a
      nickel catalyst.
AB  - Homogeneous systems for light-driven reduction of protons to H(2) typically
      suffer from short lifetimes because of decomposition of the light-absorbing
      molecule. We report a robust and highly active system for solar hydrogen
      generation in water that uses CdSe nanocrystals capped with dihydrolipoic acid
      (DHLA) as the light absorber and a soluble Ni(2+)-DHLA catalyst for proton
      reduction with ascorbic acid as an electron donor at pH = 4.5, which gives
      >600,000 turnovers. Under appropriate conditions, the precious-metal-free system
      has undiminished activity for at least 360 hours under illumination at 520
      nanometers and achieves quantum yields in water of over 36%.

PMID- 23138980
TI  - Acute inflammation initiates the regenerative response in the adult zebrafish
      brain.
AB  - The zebrafish regenerates its brain after injury and hence is a useful model
      organism to study the mechanisms enabling regenerative neurogenesis, which is
      poorly manifested in mammals. Yet the signaling mechanisms initiating such a
      regenerative response in fish are unknown. Using cerebroventricular
      microinjection of immunogenic particles and immunosuppression assays, we showed
      that inflammation is required and sufficient for enhancing the proliferation of
      neural progenitors and subsequent neurogenesis by activating injury-induced
      molecular programs that can be observed after traumatic brain injury. We also
      identified cysteinyl leukotriene signaling as an essential component of
      inflammation in the regenerative process of the adult zebrafish brain. Thus, our
      results demonstrate that in zebrafish, in contrast to mammals, inflammation is a
      positive regulator of neuronal regeneration in the central nervous system.

PMID- 23138983
TI  - On-demand patterning of nanostructured pentacene transistors by scanning thermal
      lithography.
AB  - Thermal scanning lithography is used to pattern semiconducting nanoribbon-like
      pentacene structures with ultrahigh spatial resolution onto arbitrary substrates
      in air. The method allows control of the pentacene crystal growth direction and
      domain-size distribution. By combining these quasi-one-dimensional nanoribbon
      like structures with conductive electrodes and a suitable gate dielectric,
      functional p-channel transistors are demonstrated.

PMID- 23138982
TI  - Quantitative MRI and loss of free ambulation in Duchenne muscular dystrophy.
AB  - The purpose of this ethics approved trial was to correlate quantitative MRI with
      functional abilities in both ambulant and non-ambulant Duchenne muscular
      dystrophy (DMD). Twenty patients with genetically confirmed DMD were recruited.
      Physical assessment was performed using the motor function measurement (MFM)
      scale. Axial 3T MRI scans of the thighs were acquired using T1-weighted in- and
      opposed-phase images (TR = 20 ms, TE1 = 2.45 ms, TE2 = 3.68 ms, flip angle = 15
      degrees ) to calculate the relative fat fraction according to the two-point Dixon
      method in the knee extensors, flexors, and adductor muscles. The average MFM was
      65.3 % and correlated negatively to age (r (2) = 0.60). Overall mean fat fraction
      correlated positively to age (r (2) = 0.51-0.64). An average of 5 % increase in
      mean fat fraction per year was calculated. Mean fat fraction of the quadriceps
      showed a high negative correlation (r (2) = 0.93) to the D1 (standing position
      and transfers) component of the MFM. A cutoff for mean fat fraction of 50 %
      predicted loss of ambulation with a sensitivity of 100 % and a specificity of 91
      %. Therefore, quantitative muscle MRI seems to be a promising endpoint for short
      clinical trials evaluating the effect of newer treatments on the time of loss of
      ambulation in DMD.

PMID- 23138981
TI  - Cytoplasmic ATP hydrolysis powers transport of lipopolysaccharide across the
      periplasm in E. coli.
AB  - Millions of molecules of lipopolysaccharide (LPS) must be assembled on the
      Escherichia coli cell surface each time the cell divides. The biogenesis of LPS
      requires seven essential lipopolysaccharide transport (Lpt) proteins to move LPS
      from the inner membrane through the periplasm to the cell surface. However, no
      intermediate transport states have been observed. We developed methods to observe
      intermediate LPS molecules bound to Lpt proteins in the process of being
      transported in vivo. Movement of individual LPS molecules along these binding
      sites required multiple rounds of adenosine triphosphate (ATP) hydrolysis in
      vitro, which suggests that ATP is used to push a continuous stream of LPS through
      a transenvelope bridge in discrete steps against a concentration gradient.

PMID- 23138984
TI  - The prevalence of problem gambling in Denmark in 2005 and 2010: a
      sociodemographic and socioeconomic characterization.
AB  - Gambling is a worldwide phenomenon. For most persons this causes only small or no
      problems, but for some, pathological gambling can be the result of entering the
      gambling environment. The objectives were to estimate the past year and lifetime
      prevalence of problem gambling in the adult Danish population (16 years or older)
      in 2010 and trends since 2005 and, furthermore, to investigate whether problem
      gamblers differed from non-problem gamblers with regard to sociodemographic and
      socioeconomic factors. Data were derived from two national representative Danish
      health surveys. The survey in 2005 was based on region-stratified random sample
      of 10,916 Danish citizens (response rate: 52.1 %) and the survey in 2010 was
      based on a random sample of 23,405 Danish citizens (response rate: 62.7 %).
      Problem gambling was defined using the lie/bet questionnaire. The past year
      prevalence of problem gamblers in Denmark remained stable from 2005 to 2010 (0.9
      and 0.8 %, respectively). The highest past year prevalence of problem gamblers
      was found among young men in both 2005 and 2010. Furthermore, problem gamblers
      were more prevalent among men, disability pensioners, less educated and those not
      married or cohabiting. The present study indicates that a high level of education
      and being employed have a protective effect against problem gambling. More
      research is needed in order to understand what attracts and maintains the
      interest of men in gambling environments as well as why women are not occupied by
      gambling in the same degree as men. 

PMID- 23138985
TI  - Chronic kidney disease in adolescent and adult patients with phenylketonuria.
AB  - OBJECTIVES: A lifelong phenylalanine-restricted diet with supplementation of a
      phenylalanine-free amino acid formula is recommended in patients with
      phenylketonuria (PKU). The effect of a long-term PKU diet on renal function and
      blood pressure has not been investigated yet. DESIGN: We analyzed renal function
      in 67 patients with PKU, aged 15-43 years, by measuring glomerular filtration
      rate (GFR) and effective renal plasma flow by isotope clearance ((51)Cr-EDTA,
      (123)J-Hippuran), estimated GFR, blood retention parameters, urinary protein and
      electrolyte excretion. Renal ultrasound and 24 h ambulatory blood pressure
      monitoring were performed additionally. Patients were divided into three groups
      according to their: 1) current diet (CD), i.e., daily protein intake: ICD <0.8
      g/kg, IICD 0.8-1.04 g/kg, IIICD >1.04 g/kg; 2) life-long diet time (LDT), i.e.,
      cumulative years of life in which daily protein intake exceeded dietary
      recommendations: ILDT <15 years, IILDT 15-19 years, IIILDT >19 years. RESULTS:
      GFR was decreased in 19 % of the patients. With increasing protein intake, GFR
      decreased significantly (ICD 111 ml/min; IICD 105 ml/min; IIICD 99 ml/min. ILDT
      112 ml/min; IILDT 103 ml/min; IIILDT 99 ml/min). Proteinuria was detected in 31
      %, microalbuminuria in 7 %, and hypercalciuria in 23 % of the patients. 23 % of
      the patients had arterial hypertension, and 41 % revealed a nocturnal non-dipping
      status. CONCLUSIONS: In patients with PKU on a lifelong diet we could detect
      impaired renal function in 19 %, proteinuria in 31 %, and arterial hypertension
      in 23 %. Thus, chronic kidney disease may develop in PKU patients, and routine
      renal function tests should be performed during long-term follow-up.

PMID- 23138988
TI  - Fumarylacetoacetate inhibits the initial step of the base excision repair
      pathway: implication for the pathogenesis of tyrosinemia type I.
AB  - Hereditary tyrosinemia type I (HT1) is an autosomal recessive disease caused by a
      deficiency in human fumarylacetoacetate (FAA) hydrolase (FAH), which is the last
      enzyme in the catabolic pathway of tyrosine. Several reports suggest that
      intracellular accumulation of intermediates of tyrosine catabolism, such as FAA
      and succinylacetone (SA) is important for the pathogenesis in liver and kidney of
      HT1 patients. In this work, we examined the effect of FAA and SA on DNA
      glycosylases initiating base excision repair (BER), which is the most important
      pathway for removing mutagenic DNA base lesions. In vitro assays monitoring DNA
      glycosylase activities demonstrated that FAA but not SA inhibited base removal.
      In particular, the Neil1 and Neil2 DNA glycosylases were strongly inhibited,
      whereas inhibition of Nth1 and Ogg1 were less efficient. These DNA glycosylases
      initiate excision of a broad range of mutagenic oxidative base lesions. Further,
      FAA showed a modest inhibitory effect on the activity of the alkylbase DNA
      glycosylase Aag and no significant inhibition of the uracil DNA glycosylase Ung2.
      These data indicate that FAA inhibition of DNA glycosylases removing oxidative
      base lesions in HT1 patients may increase mutagenesis, suggesting an important
      mechanism for development of hepatocarcinoma and somatic mosaicism. 

PMID- 23138989
TI  - Important aspects in the molecular diagnosis of mucopolysaccharidoses.

PMID- 23138986
TI  - Demographics, diagnosis and treatment of 256 patients with tetrahydrobiopterin
      deficiency in mainland China: results of a retrospective, multicentre study.
AB  - BACKGROUND: National coverage of neonatal screening for hyperphenylalaninaemia
      (HPA) in China is still low and tests to differentiate causes of HPA are not
      performed in many centres. This study aimed to describe the demographics,
      geographic distribution, diagnosis, treatment and clinical outcomes of treatment,
      including intellectual development, in patients with tetrahydrobiopterin (BH4)
      deficiency in mainland China. METHODS: This was a retrospective, multicentre,
      chart review in patients with BH4 deficiency across mainland China born 1985
      2010. RESULTS: Two hundred fifty six patients were included; 59.9 % (267/446) of
      parents were from eastern China. Median (interquartile range) age at diagnosis
      decreased from 12.0 (5.5, 102.0) months to 2.0 (1.0, 3.5) months in patients born
      1985-1999 (n = 28) and 2005-2010 (n = 152), respectively. 6-Pyruvoyl
      tetrahydropterin synthase (PTPS) deficiency was the primary cause of BH4
      deficiency (96.0 %); four hotspot mutations accounted for 76.6 % of PTS gene
      mutations; two novel variants in the QDPR gene were identified. Most patients
      (83.6 %) received treatment with BH4, L-dopa, 5-hydroxytryptophan and/or diet
      therapy. Target blood Phe concentration was confirmed at 88.9 % of visits; median
      (Q1, Q3) blood Phe concentration was 106.8 (73.0, 120.0) MUmol/L during therapy
      and 117.0 (67.1, 120.0) MUmol/L at last visit. Median (Q1, Q3) WISC IQ score was
      80.0 (69.0, 90.0) in 33 patients. DQ scores were within normal range (>=85) for
      37/59 (62.7 %) patients. Physical development indicators were within normal
      ranges. Treatment-related adverse events, reported in 20/256 (7.8 %) patients,
      were mild-to-moderate in severity. CONCLUSION: This study provides valuable
      information on the current and historical situation of BH4 deficiency in mainland
      China.

PMID- 23138990
TI  - Bmi1 knockdown inhibits hepatocarcinogenesis.
AB  - Although Bmi1 is well established as one of the most commonly activated
      oncogenes, the precise role of Bmi1 during hepatocarcinogenesis remains unclear.
      In addition, Bmi1 provides a potential therapeutic target for the future
      treatment of hepatocellular carcinoma (HCC). In this study, the expression of
      Bmi1 in HCC tissues was evaluated by immunohistochemistry and western blot
      analysis. We found that Bmi1 was much more highly expressed in HCC tissue
      compared to normal liver tissue. The shRNA-mediated knockdown of Bmi1 was used to
      assess the effects of Bmi1 in hepatocarcinogenesis. Bmi1 downregulation reduced
      cell growth and tumorsphere formation in vitro. A cell cycle analysis using flow
      cytometry clarified that Bmi1 knockdown blocked the cell cycle transition from
      the G0/G1 to the S phase. Additionally, the Bmi1 knockdown led to reduced
      tumorigenicity in vivo. Furthermore, Bmi1 expression enhanced the sensitivity of
      HCC to the therapeutic agent, sorafenib. Taken together, the current results
      demonstrate that Bmi1 functions as a promoter in cell proliferation and
      hepatocarcinogenesis, providing a potential therapeutic target for the future
      treatment of HCC.

PMID- 23138991
TI  - Synthesis and duplex-forming ability of oligonucleotides containing 4'
      carboxythymidine analogs.
AB  - Oligonucleotides containing 4'-carboxy-, 4'-methoxycarbonyl-, 4'-carbamoyl-, and
      4'-methylcarbamoyl-thymidines, and their 2'-methoxy, 2'-amino or 2'-acetamido
      analogs were prepared. Their duplex-forming ability with DNA and RNA complements
      was evaluated by UV melting experiments. Interestingly, 4'-carboxythymidine
      existing in the S-type sugar conformation was found to lead to an increase in the
      stability of the duplex formed with RNA complements compared to natural
      thymidine.

PMID- 23138992
TI  - Effects of hemoperitoneum on wound healing and fibrinolytic activity in colonic
      anastomosis.
AB  - BACKGROUND: We aimed to test whether hemoperitoneum has adverse effects on
      colonic anastomosis healing by increasing fibrinolytic activity. METHODS: After
      colonic intersection and anastomosis, 20 Wistar Albino rats received
      intraabdominal injections of either 25 mg/kg blood (10, Group 1) or physiologic
      saline (10, Group 2). Anastomotic bursting pressures were measured after
      sacrifice on the fifth day. Following histopathological evaluation of the
      anastomotic line, hydroxyproline, tissue plasminogen activator (tPA), plasminogen
      activator inhibitor-1 (PAI-1), and tPA/PAI-1 complex levels were determined in
      the omentum, lung and anastomotic colon. RESULTS: Mean anastomotic bursting
      pressures of Groups 1 and 2 were 224.5 mmHg and 254.4 mmHg (p=0.121), and mean
      hydroxyproline levels were 45.89 and 65.959 mg/g protein, respectively (p=0.257).
      Histopathology was insignificant. There was a significant difference between
      groups in omental tPA levels (0.962 ng/ml and 0.27 ng/ml, p=0.041), but not in
      PAI-1 and tPA/PAI-1. Anastomotic line and lung levels of tPA, PAI-1 and tPA/PAI-1
      complex were not significantly different between groups. The relation between
      anastomotic line tPA level and bursting pressure was highly significant in Group
      2 (r=0.778; p=0.008). CONCLUSION: In this first study on the effect of
      hemoperitoneum on colonic anastomosis, we observed no significant effect on
      anastomotic healing or fibrinolytic activity, except in the omentum. Further
      studies with different blood volumes and assessment times are needed.

PMID- 23138993
TI  - The relationship of trauma severity and mortality with cardiac enzymes and
      cytokines at multiple trauma patients.
AB  - BACKGROUND: In this study, we aimed to determine the effects of trauma severity
      on cardiac involvement through evaluating the trauma severity score together with
      diagnostic tests in multiple trauma patients. A trauma score was determined using
      various trauma severity scales. METHODS: After obtaining the approval of the
      ethics committee of the faculty, this prospective study was performed through
      evaluating 100 multiple trauma patients, aged over 15 years, who applied to our
      Emergency Department (ED). After determining the trauma severity score using
      instruments such as the Injury Severity Score (ISS), Glasgow Coma Scale (GCS),
      and Revised Trauma Score (RTS), the cardiac condition was evaluated using
      biochemical and radiological diagnostic tests. RESULTS: During the study period,
      100 patients were evaluated (78 male, 22 female; mean age: 33.2+/-15.4; range 15
      to 70 years). It was determined that 92 (92%) were blunt trauma cases, and 77
      (77%) of them were due to traffic accidents. The majority of cases showed
      electrocardiogram (ECG) abnormalities (63%) and sinus tachycardia (36%). Abnormal
      echocardiogram (ECHO) findings, mostly accompanied by ventricular defects (n=24),
      were determined in 31 of the cases. Nineteen cases with high trauma severity
      score resulted in death, and 14 of all deaths were secondary to traffic
      accidents. Trauma scores were found to show a significant difference between the
      two groups. CONCLUSION: The ISS trauma scale was determined to be the most
      effective in terms of indicating heart involvement in patients with multiple
      traumas. Close follow-up and cardiac monitoring should be applied to patients
      with high trauma severity scores considering possible cardiac rhythm changes and
      hemodynamic disturbances due to cardiac involvement.

PMID- 23138994
TI  - Burn unit: colonization of burn wounds and local environment.
AB  - BACKGROUND: We present the results of a comparative prospective study of the
      resistance profile of strains isolated from pathological material of patients
      hospitalized in the burn unit of the military hospital in Rabat and from their
      environment over a period of one and a half years (July 2009-February 2011).
      METHODS: The study concerned 125 pathological products from patients (40 men, 20
      women; mean age 38+/-14.8 years; range 2 to 80 years) hospitalized with burns.
      This allowed the isolation of 86 non-redundant bacterial strains during the first
      period and 50 during the second. RESULTS: The dominant species were Acinetobacter
      baumannii (15.6%), followed by Pseudomonas aeruginosa (13.8%) and Staphylococcus
      aureus (11%). During the second period, we noted the abundance of A. baumannii
      (15.5%), followed by P. aeruginosa (11.3%) and Klebsiella pneumoniae (8.5%). Of
      the 104 environmental samples of burn patients, 139 microorganisms were isolated.
      Coagulase-negative staphylococcus was the most abundant strain in the two study
      periods (69.2% and 64.6%). CONCLUSION: All species showed an almost identical
      sensitivity to the various antibiotics tested.

PMID- 23138995
TI  - Cardiac monitoring in patients with electrocution injury.
AB  - BACKGROUND: The necessity of admitting patients exposed to electrocution injuries
      for monitoring and observation in the emergency department (ED) remains
      controversial. METHODS: We evaluated the medical records of 102 patients (86
      male, 16 female; median age 29.5; range 18 to 68 years) admitted to the adult ED
      with electrocution injuries over the past 20 years. RESULTS: Only 9 deaths were
      reported: 3 as a result of contact with low-voltage electricity and 6 after
      contact with high-voltage electricity. With the exception of a case of sepsis,
      all deaths were related to early rhythm abnormalities immediately following the
      incident. The ECG findings of surviving patients in the study group were as
      follows: 70 normal, 8 sinus tachycardia, 3 sinus bradycardia, 4 ST-T wave
      changes, and 1 ventricular extrasystole. ECG recordings of 7 patients could not
      be found. 72 cases had been followed up with repeat ECG recordings. There were no
      observed ECG changes requiring any medical or electrical therapies in the
      surviving patients. CONCLUSION: Cardiac rhythm abnormalities related to
      electrocution injuries are usually observed at the time of the incident. If the
      patient's overall clinical condition is good and they have a normal ECG at the
      time of admission to the ED, the probability of observing any delayed serious
      dysrhythmia is unlikely.

PMID- 23138996
TI  - [A life-saving approach after thoracic trauma: emergency room thoracotomy].
AB  - BACKGROUND: In this article, the outcomes, indications and methods of emergency
      department service resuscitative thoracotomy in cardiac and/or respiratory arrest
      patients after thoracic trauma are discussed. METHODS: Between January 2004 and
      December 2010, nine resuscitative thoracotomies were performed after thoracic
      trauma in the emergency department of our hospital. The records of the patients
      were evaluated retrospectively. RESULTS: A total of nine patients underwent
      resuscitative thoracotomy: five stab wounds, two traffic accidents, one fall from
      height, and one gunshot wound. Anterolateral thoracotomy in supine position was
      performed in all. Three patients had lung parenchymal laceration, three patients
      had cardiac laceration, two patients had intercostal vessel injury, and one
      patient had descending aorta injury. None of the four patients with blunt trauma
      recovered. Three of five patients with penetrating trauma were discharged after
      an average of eight days of follow-up, whereas two of them were lost
      perioperatively. CONCLUSION: Emergency room thoracotomy can be performed in
      thoracic trauma cases who are in shock and have unresponsive hypotension despite
      large volume fluid and blood replacement and no time for transportation to the
      operating room. The results are better in penetrating trauma patients than in
      blunt trauma.

PMID- 23138997
TI  - Is total-subtotal colectomy and primary anastomosis a good treatment alternative
      in malignant obstructive lesions of the left colon?
AB  - BACKGROUND: This study was designed in order to compare the effectiveness of
      subtotal-total colectomy with other surgical methods in the treatment of
      malignant obstructive lesions of the left colon. METHODS: Patients admitting with
      symptoms of colonic obstruction and treated by emergency surgery in Konya
      Education and Research Hospital between 2004 and 2007 were enrolled. Patients
      were divided into three groups according to the surgical procedures (Group I:
      Hartmann procedure; Group II: resection + diverting ileostomy; Group III: total
      subtotal colectomy). Related patient data were evaluated retrospectively.
      RESULTS: The mean age of 62 patients was 64 (38-89) years. There were no
      significant differences between the groups with respect to gender, age, American
      Society of Anesthesiology scores, and tumor stages. There were no significant
      differences between the study groups in terms of operative duration,
      postoperative mortality, and five-year survival; however, the length of hospital
      stay and hospitalization costs were lower in Group III compared to the other
      groups. CONCLUSION: We suggest that subtotal-total colectomy performed by
      experienced surgeons may be a good alternative to the other procedures.

PMID- 23138998
TI  - [The factors affecting the development of phthisis bulbi after penetrating eye
      injuries].
AB  - BACKGROUND: We aimed to investigate the factors affecting the development of
      phthisis bulbi after penetrating eye injuries. METHODS: The medical records of
      132 patients admitted to our clinic between 2000-2006 with the diagnosis of
      penetrating eye injury were collected. The records of the eight patients who
      developed phthisis bulbi were evaluated retrospectively. The aspects of anatomic
      localization, type of trauma, associated events, and development of phthisis
      bulbi were also investigated. RESULTS: The mean age of the eight patients (5
      males, 3 females) was 7.12+/-4.70 years (range: 2-16 years) and the mean follow
      up time was 2.06+/-1.47 years (range: 6 months-5 years). Three of eight patients
      developed post-perforation endophthalmitis. Three patients had zone 2-3 scleral
      perforation and associated retinal detachment and the remaining two patients had
      proliferative vitreoretinopathy according to the trauma; all eight patients
      eventually developed phthisis bulbi. The mean time for the development of
      phthisis bulbi was 5.5+/-2.13 months (range: 3-10 months). CONCLUSION: After
      penetrating eye injuries, visual prognosis and development of phthisis bulbi were
      affected significantly by the factors including anatomic localization, size of
      the injury, associated anterior or posterior segment pathologies, and
      endophthalmitis secondary to the trauma.

PMID- 23138999
TI  - Ocular trauma score in transferred fireworks-related ocular injuries: a case
      series.
AB  - BACKGROUND: Our aim was to review the characteristics of transferred fireworks
      related ocular damage and to evaluate the prognostic value of the ocular trauma
      score (OTS) for these injuries. METHODS: This study included 22 transferred
      patients (19 male, 3 female; mean age 22.6+/-14.9 years) (25 eyes). The data were
      retrospectively reviewed, including the characteristics of the geography, types
      of fireworks, status of injuries, therapeutic procedures, and the best-corrected
      visual acuity (BCVA). All the injured eyes were classified using the OTS at the
      time of the initial examination. RESULTS: Twenty eyes (80%) were in OTS category
      1, three eyes (12%) were in OTS category 2, and two eyes (8%) were in OTS
      category 3. All cases received surgical therapy. Six eyes (24%) were enucleated,
      four (16%) of which achieved an improvement in their final BCVA. There was a
      statistically significant improvement in final BCVA between OTS category 1 and
      the other two OTS categories (p=0.016). CONCLUSION: The aforementioned
      transferred fireworks-related ocular injury cases occurred mainly in young
      adults, men and active participants, all of which incurred serious vision loss
      and blindness. The OTS is quite effective for classifying the status and
      estimating the prognosis of transferred fireworks-related ocular injuries.

PMID- 23139000
TI  - Are we prepared for orthopedic trauma surgery outside normal working hours? A
      retrospective analysis.
AB  - BACKGROUND: This retrospective analysis was done to determine whether there is a
      change in outcomes of trauma patients undergoing intramedullary nailing (IMN) for
      femur and tibia fracture as an emergency versus elective procedure. METHODS: Data
      were collected for all patients admitted to male orthopedic wards between 1
      January 2004 and 30 June 2009 with femur and tibia fractures that required IMN.
      The data collected included surgery undertaken on as emergency or elective
      procedure, duration of surgery, complications encountered, and union status of
      fracture. RESULTS: There were 431 fractures of the tibia, fibula and femur.
      Operating time for femur fracture as an emergency procedure was significantly
      greater than for elective surgery (191+/-79 versus 155+/-65 minutes; p<=0.001,
      confidence interval [CI] -19.54). For tibia fracture, operating times were
      167.1+/-62 versus 69.2+/-35 minutes (p<0.001, CI <-85.4). Complications of
      infection, secondary surgery and of union were more common in emergency
      procedures than elective surgeries. CONCLUSION: This study shows that
      complications are higher in emergency surgery than elective surgery due to the
      increase in the duration of surgery. This is attributed to the non-availability
      of dedicated trained orthopedic nursing staff and theater during emergency
      procedures. We believe that it is time to develop dedicated orthopedic trauma
      theaters in hospitals that treat emergency fracture fixations.

PMID- 23139001
TI  - Management of inhalation injury and respiratory complications in Burns Intensive
      Care Unit.
AB  - BACKGROUND: Inhalation injury has high mortality and carries a significant risk
      of permanent pulmonary dysfunction. Inhalation injury and its consequences impose
      difficulties for the respiratory therapists, nurses and doctors who play a
      central role in its clinical management. In this study, we aimed to report our
      clinical experience and the role of non-invasive mechanic ventilatory (NIMV)
      support in a series of inhalation-injured patients. METHODS: Patients
      hospitalized at Ankara Numune Training and Research Hospital's Burns Intensive
      Care Unit between March 2009 and March 2011 was reviewed, and patients with
      required respiratory support due to inhalation injury were included in the study.
      RESULTS: Among the patients, 37 had inhalation injury, and their mortality was
      13.5%. Of the 37 patients, 16 had mandatory intubation (6 in the first 6 hours
      and 10 in the clinical course); however, others (67.8%) had only NIMV support.
      CONCLUSION: Application of NIMV support with proper modes decreases the need for
      invasive procedures in inhalation-injured patients. Based on our results, we
      propose the application of NIMV support in inhalation-injured burn patients.

PMID- 23139002
TI  - The impact of Ramadan on peptic ulcer perforation.
AB  - BACKGROUND: Medical treatment has played an important role in the reduction of
      peptic ulcer perforation (PUP). The goal of this study was to evaluate the effect
      of fasting on PUP. METHODS: A retrospective analysis of 229 patients who were
      operated due to PUP between 1999-2009 was made. Patients were divided into two
      groups. Group I (n=188) included the patients who were operated in other periods
      of the year, while Group II (n=41) included the patients who were operated during
      Ramadan, the Muslim period of fasting. Patients in Group II were analyzed in
      terms of duration of fasting. RESULTS: The increase in surgeries per group was
      higher in Group II than Group I (p<0.05). Predisposing factors, anti-ulcer drug
      usage and demographic variables were seen to have no role in this difference.
      Duration of fasting may have a minimal effect on the perforation. CONCLUSION: The
      results of this study demonstrate that PUP is detected as relatively higher
      during Ramadan among those who are fasting for more than 12 hours daily. We
      suggest that people with predisposing factors should be informed before making a
      decision to fast.

PMID- 23139003
TI  - Surgical treatment of a case with rapidly growing mass lesion after trauma: on
      the left forearm arteriovenous malformation.
AB  - In this case, we report a vascular malformation with high flow pattern
      complicated with trauma. A postoperative histopathology examination confirmed an
      arterio-venous malformation in specimens of surgical excision material. In our
      opinion, posttraumatic progression of a vascular malformation is an emergency and
      requires an urgent evaluation with surgery at any localization of the body.

PMID- 23139004
TI  - Cerebral infarction caused by traumatic carotid artery dissection.
AB  - Traumatic carotid artery dissection, if not diagnosed and treated early, is a
      serious problem with permanent neurological deficit and a high mortality rate of
      up to 40%. We present a case with delayed diagnosis of traumatic carotid artery
      dissection in a 21-year-old female. While there were no ischemic infarct findings
      on the admission cerebral computerized tomography (CT), such findings were
      observed on two cerebral CTs taken because of the left hemiplegia noticed seven
      days later when the patient regained consciousness. The patient was referred to
      our emergency service, and definitive diagnosis was achieved with arterial
      Doppler ultrasonography, cerebral magnetic resonance imaging (MRI), diffusion
      MRI, and MR angiography. We did not consider invasive treatment since the
      neurological damage was permanent and dissection grade was IV according to
      angiography findings. The case was discharged within a week and physiotherapy was
      advised. Despite the advances in diagnostic methods, diagnosis of traumatic
      carotid artery dissection is still missed or delayed, as in the case presented
      here. Early diagnosis can ameliorate permanent neurological damage or even
      prevent it. However, the vital factors for early diagnosis are the obtained
      anamnesis leading to appropriate radiological examinations, detailed physical
      examination and high clinical suspicion.

PMID- 23139005
TI  - Ileus due to Meckel's diverticulum: case reports.
AB  - Meckel's diverticulum is the most common congenital anomaly of the small
      intestine, with an estimated incidence of approximately 1-3% in the general
      population. Intestinal obstruction is the most common complication in adult
      patients. Since accurate diagnosis before the operation is difficult, decision
      for surgery is delayed, and serious problems may be encountered. Here in, we
      present the diagnosis and management of our patients with intestinal obstruction
      due to Meckel's diverticulum.

PMID- 23139006
TI  - Bilateral asymmetric traumatic hip dislocation with bilateral acetabular
      fracture: case report.
AB  - Bilateral traumatic hip dislocation is a very rare condition. Simultaneous
      anterior and posterior traumatic dislocation of both hips is even more unusual. A
      case report of a bilateral asymmetrical hip joint dislocation with bilateral
      acetabular fracture in a 28-year-old man is presented.

PMID- 23139007
TI  - Perforation of Meckel's diverticulum by a button battery: report of two cases.
AB  - Ingested button battery perforation of Meckel's diverticulum is extremely rare,
      with only two reported cases in the recent literature. Two additional preschool
      children who accidentally swallowed an alkaline button battery and developed a
      perforated Meckel's diverticulum are reported. Surgeons should be aware of this
      rare complication. Careful clinical, radiologic and laboratory monitoring of
      children who ingest a button battery is advisable.

PMID- 23139008
TI  - Subcutaneous emphysema and pneumomediastinum complicating a dental procedure.
AB  - Cervicofacial emphysema and pneumomediastinum are rarely observed complications
      of dental interventions. The complications are associated with the use of a high
      speed air-turbine dental drill. It is a potentially life-threatening condition,
      but the majority of cases are self-limiting and benign. We describe a patient
      with remarkable subcutaneous emphysema, pneumomediastinum, and partial
      pneumothorax after right second mandibular molar extraction. Dentists and
      physicians more often attribute the rapid onset of dyspnea in patients after a
      dental procedure to an allergic reaction to the anesthesia used during the
      procedure. Dentists and physicians should be aware that soft tissue emphysema can
      cause acute swelling of the cervicofacial region after dental procedures, which
      may mimic an allergic reaction.

PMID- 23139009
TI  - Late-onset spinal accessory nerve palsy after traffic accident: case report.
AB  - An injury to the spinal accessory nerve is mostly reported after surgical
      procedures performed in the posterior triangle of the neck. In addition, it may
      be caused by fractures in the jugular foramina, traumas or skull base tumors.
      Clinically, paralysis of the trapezius muscle leads to weakness, downward
      rotation of the scapulae and falling down of the shoulder girdle. A 38- year-old
      male with left shoulder pain, scapular deviation and weakness in the left upper
      extremity, whose symptoms developed over a two-year period following a traffic
      accident, is presented herein. In the electromyography (EMG) study, partial
      spinal accessory nerve palsy was detected. The patient was treated conservatively
      for the nerve palsy since the time elapsed rendered surgical intervention
      inappropriate. We report a case in which spinal accessory nerve palsy developed
      two years after a traffic accident. Accessory nerve injury following a traffic
      accident is very uncommon.

PMID- 23139010
TI  - High yield, reproducible and quasi-automated bilayer formation in a microfluidic
      format.
AB  - A microfluidic platform is reported for various experimentation schemes on cell
      membrane models and membrane proteins using a combination of electrical and
      optical measurements, including confocal microscopy. Bilayer lipid membranes
      (BLMs) are prepared in the device upon spontaneous and instantaneous thinning of
      the lipid solution in a 100-MUm dry-etched aperture in a 12.5-MUm thick Teflon
      foil. Using this quasi-automated approach, a remarkable 100% membrane formation
      yield is reached (including reflushing in 4% of the cases), and BLMs are stable
      for up to 36 h. Furthermore, the potential of this platform is demonstrated for
      (i) the in-depth characterization of BLMs comprising both synthetic and natural
      lipids (1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhPC) and L-alpha
      phosphatidylcholine (L-alpha-PC)/cholesterol, respectively) in terms of seal
      resistance, capacitance, surface area, specific capacitance, and membrane
      hydrophobic thickness; (ii) confocal microscopy imaging of phase separation in
      sphingomyelin/L-alpha-PC/cholesterol ternary membranes; (iii) electrical
      measurements of individual nanopores (alpha-hemolysin, gramicidin); and (iv)
      indirect assessment of the alteration of membrane properties upon exposure to
      chemical stimuli using the natural nanopore gramicidin as a sensor.

PMID- 23139011
TI  - Fall incidence and outcomes of falls in a prospective study of adults with
      rheumatoid arthritis.
AB  - OBJECTIVE: To determine the incidence of falls and to investigate the
      consequences of falls in adults with rheumatoid arthritis (RA). METHODS: A total
      of 559 community-dwelling adults with RA, ages 18-88 years (mean age 62 years,
      69% women), participated in this prospective cohort study. After a detailed
      clinical assessment, patients were followed for 1 year, using monthly falls
      calendars and followup telephone calls. Followup took place in the participant's
      usual place of residence in the Northwest of England. Outcome measures included
      fall occurrence, reason for fall, type and severity of injuries, fractures, fall
      location, lie-times, use of health services, and functional ability. RESULTS: A
      total of 535 participants followed for 1 year had a total of 598 falls. Of these
      participants, 36.4% (95% confidence interval 32%-41%) reported falling during the
      1-year followup period, with an incidence rate of 1,313 per 1,000 person-years at
      risk or 1.11 falls per person. Age and sex were not associated with falls. More
      than one-third of the falls were reportedly caused by hips, knees, or ankle
      joints "giving way." More than half of all the falls resulted in moderate
      injuries, including head injuries (n = 27) and fractures (n = 26). Treatment by
      general practitioners or other health professionals was required for 15.0% of
      falls, and emergency services were required for 8.8% of falls. CONCLUSION: These
      results indicate that adults with RA are at high risk of falls and fall-related
      injuries, fractures, and head injuries. Strategies to prevent falls in adults
      with RA must be prioritized to reduce falls, fall-related injuries, and
      fractures.

PMID- 23139013
TI  - Semantic distance abnormalities in mild cognitive impairment: their nature and
      relationship to function.
AB  - OBJECTIVE: The authors sought to directly examine compromises in the semantic
      system in mild cognitive impairment and their possible relationship to everyday
      functional competencies. METHOD: Study participants were 25 patients who met
      criteria for amnestic mild cognitive impairment, 27 patients with mild or
      moderate Alzheimer's disease, and 70 healthy comparison subjects. The authors
      administered a novel semantic distance task in which participants make decisions
      about word or image stimuli that correspond to real-world entities that differ in
      physical size. The authors also administered a performance-based measure of
      everyday functional competence. RESULTS: Participants in the mild cognitive
      impairment and Alzheimer's groups were consistently less accurate and slower than
      healthy comparison subjects in semantic decisions in which words were used as
      stimuli. When these participants had to make more fine-grained decisions about
      the semantic attribute of size, their performance in accuracy and reaction time
      disproportionately worsened relative to that of comparison subjects. In image
      based conditions in which line drawings were used as stimuli, sensory-perceptual
      information (i.e., the size of the drawings themselves) had undue influence over
      semantic knowledge judgments in the mild cognitive impairment and Alzheimer's
      groups. Performance in the semantic distance task was a strong and significant
      predictor of everyday functional competence in the mild cognitive impairment and
      Alzheimer's groups. CONCLUSIONS: This study synthesized several distinct strands
      in the mild cognitive impairment literature by providing evidence for 1)
      compromises in the semantic system in mild cognitive impairment, not confounded
      by overt retrieval or refractory access; 2) intrusion of perceptual information
      on semantic processing; and 3) a robust relation between semantic corruption and
      difficulties in everyday functioning.

PMID- 23139014
TI  - Profound neurological injury in a patient with atypical hemolytic uremic
      syndrome.

PMID- 23139012
TI  - Intravenous administration of granulocyte colony-stimulating factor for treating
      neuropathic pain associated with compression myelopathy: a phase I and IIa
      clinical trial.
AB  - OBJECTIVE: To confirm the feasibility and safety of granulocyte colony
      stimulating factor (G-CSF) for treating spinal neuropathic pain associated with
      compression myelopathy, we have initiated an open-label single-center prospective
      clinical trial. METHODS: Between January 2009 and February 2011, 17 patients were
      accrued and were divided into two groups. One group included 7 patients who
      complained of pain associated with worsening symptoms of myelopathy (progressing
      myelopathy-related pain group). The other group included 10 patients who
      complained of pain that persisted after surgery for compression myelopathy (post
      operative persistent pain group). All patients underwent intravenous
      administration of G-CSF (10 MUg/kg/day) for 5 consecutive days. Pain severity was
      evaluated using a visual analog scale (VAS) before and after G-CSF
      administration. RESULTS: In 14 of the 17 patients, pain was relieved within
      several days after G-CSF administration. Pain disappeared completely in 3
      patients. In the progressing myelopathy-related pain group, the mean VAS score
      was 71.4/100 before G-CSF administration, and decreased to 35.9/100 at 1 week
      after G-CSF administration (p < 0.05). In the post-operative persistent pain
      group, the mean VAS score was 72.0/100 before G-CSF administration, and decreased
      to 51.7/100 at 1 week after G-CSF administration (p < 0.05). No severe adverse
      events occurred during or after G-CSF administration. CONCLUSIONS: The present
      results provide us with the possibility that G-CSF has a pain-relieving effect
      for neuropathic pain in patients with compression myelopathy.

PMID- 23139015
TI  - New missense homozygous mutation (Q270Ter) in the pyrimidine 5' nucleotidase type
      I-related gene in two Indian families with hereditary non-spherocytic hemolytic
      anemia.

PMID- 23139016
TI  - Multiple binding modes for palmitate to barley lipid transfer protein facilitated
      by the presence of proline 12.
AB  - Molecular dynamics simulations have been used to characterise the binding of the
      fatty acid ligand palmitate in the barley lipid transfer protein 1 (LTP) internal
      cavity. Two different palmitate binding modes (1 and 2), with similar protein
      ligand interaction energies, have been identified using a variety of simulation
      strategies. These strategies include applying experimental protein-ligand atom
      atom distance restraints during the simulation, or protonating the palmitate
      ligand, or using the vacuum GROMOS 54B7 force-field parameter set for the ligand
      during the initial stages of the simulations. In both the binding modes
      identified the palmitate carboxylate head group hydrogen bonds with main chain
      amide groups in helix A, residues 4 to 19, of the protein. In binding mode 1 the
      hydrogen bonds are to Lys 11, Cys 13, and Leu 14 and in binding mode 2 to Thr 15,
      Tyr 16, Val 17, Ser 24 and also to the OH of Thr 15. In both cases palmitate
      binding exploits irregularity of the intrahelical hydrogen-bonding pattern in
      helix A of barley LTP due to the presence of Pro 12. Simulations of two variants
      of barley LTP, namely the single mutant Pro12Val and the double mutant Pro12Val
      Pro70Val, show that Pro 12 is required for persistent palmitate binding in the
      LTP cavity. Overall, the work identifies key MD simulation approaches for
      characterizing the details of protein-ligand interactions in complexes where NMR
      data provide insufficient restraints.

PMID- 23139017
TI  - Case studies for practical food effect assessments across BCS/BDDCS class
      compounds using in silico, in vitro, and preclinical in vivo data.
AB  - Practical food effect predictions and assessments were described using in silico,
      in vitro, and/or in vivo preclinical data to anticipate food effects and
      Biopharmaceutics Classification System (BCS)/Biopharmaceutics Drug Disposition
      Classification System (BDDCS) class across drug development stages depending on
      available data: (1) limited in silico and in vitro data in early discovery; (2)
      preclinical in vivo pharmacokinetic, absorption, and metabolism data at candidate
      selection; and (3) physiologically based absorption modeling using biorelevant
      solubility and precipitation data to quantitatively predict human food effects,
      oral absorption, and pharmacokinetic profiles for early clinical studies. Early
      food effect predictions used calculated or measured physicochemical properties to
      establish a preliminary BCS/BDDCS class. A rat-based preclinical BCS/BDDCS
      classification used rat in vivo fraction absorbed and metabolism data.
      Biorelevant solubility and precipitation kinetic data were generated via animal
      pharmacokinetic studies using advanced compartmental absorption and transit
      (ACAT) models or in vitro methods. Predicted human plasma concentration-time
      profiles and the magnitude of the food effects were compared with observed
      clinical data for assessment of simulation accuracy. Simulations and analyses
      successfully identified potential food effects across BCS/BDDCS classes 1-4
      compounds with an average fold error less than 1.6 in most cases. ACAT
      physiological absorption models accurately predicted positive food effects in
      human for poorly soluble bases after oral dosage forms. Integration of
      solubility, precipitation time, and metabolism data allowed confident
      identification of a compound's BCS/BDDCS class, its likely food effects, along
      with prediction of human exposure profiles under fast and fed conditions.

PMID- 23139018
TI  - A pharmacokinetic simulation tool for inhaled corticosteroids.
AB  - The pharmacokinetic (PK) behavior of inhaled drugs is more complicated than that
      of other forms of administration. In particular, the effects of certain
      physiological (mucociliary clearance and differences in membrane properties in
      central and peripheral (C/P) areas of the lung), formulation (as it relates to
      drug deposition and particle dissolution rate), and patient-related factors (lung
      function; effects on C/P deposition ratio) affect the systemic PKs of inhaled
      drugs. The objectives of this project were (1) to describe a compartmental model
      that adequately describes the fate of inhaled corticosteroids (ICS) after
      administration while incorporating variability between and within subjects and
      (2) based upon the model, to provide a freely available tool for simulation of PK
      trials after ICS administration. This compartment model allows for mucociliary
      removal of undissolved particles from the lung, distinguishes between central and
      peripheral regions of the lung, and models drug entering the systemic circulation
      via the lung and the gastrointestinal tract. The PK simulation tool is provided
      as an extension package to the statistical software R ('ICSpkTS'). It allows
      simulation of PK trials for hypothetical ICS and of four commercially available
      ICS (budesonide, flunisolide, fluticasone propionate, and triamcinolone
      acetonide) in a parallel study design. Simulated PK data and parameters agreed
      well with literature data for all four ICS. The ICSpkTS package is especially
      suitable to explore the effect of changes in model parameters on PK behavior and
      can be easily adjusted for other inhaled drugs.

PMID- 23139019
TI  - The utility of modeling and simulation approaches to evaluate immunogenicity
      effect on the therapeutic protein pharmacokinetics.
AB  - While therapeutic proteins (TP), particularly recombinant human proteins and
      fully human monoclonal antibodies, are designed to have a low immunogenic
      potential in humans, a clinical immune response does sometimes occur and cannot
      be predicted from preclinical studies. Changes in TP pharmacokinetics may be
      perceived as an early indication of antibody formation and serve as a surrogate
      for later changes in efficacy and safety in individual subjects. Given the
      substantial increase in number of biological products, including biosimilars,
      there is an urgent need to quantitatively predict and quantify the immune
      response and any consequential changes in TP pharmacokinetics. The purpose of
      this communication is to review the utility of population-based modeling and
      simulation approaches developed to date for investigating the development of an
      immune response and assessing its impact on TP pharmacokinetics. Two examples of
      empirical modeling approaches for pharmacokinetic assessment are presented. The
      first example presents methods to analyze pharmacokinetic data in the presence of
      anti-drug antibody (ADA) and confirm the effect of immunogenicity on TP
      pharmacokinetics in early phases of drug development. The second example provides
      a framework to analyze pharmacokinetic data in the absence or with very low
      incidence of ADA and confirm with enough power the lack of an immunogenicity
      effect on TP pharmacokinetics in late phases of drug development. Finally, a
      theoretical mechanism-based modeling framework is presented to mathematically
      relate the complex interaction among TP, their targets, and ADA.

PMID- 23139020
TI  - Determination of the dominant arachidonic acid cytochrome p450 monooxygenases in
      rat heart, lung, kidney, and liver: protein expression and metabolite kinetics.
AB  - Cytochrome P450 (P450)-derived arachidonic acid (AA) metabolites serve pivotal
      physiological roles. Therefore, it is important to determine the dominant P450 AA
      monooxygenases in different organs. We investigated the P450 AA monooxygenases
      protein expression as well as regioselectivity, immunoinhibition, and kinetic
      profile of AA epoxygenation and hydroxylation in rat heart, lung, kidney, and
      liver. Thereafter, the predominant P450 epoxygenases and P450 hydroxylases in
      these organs were characterized. Microsomes from heart, lung, kidney, and liver
      were incubated with AA. The protein expression of CYP2B1/2, CYP2C11, CYP2C23,
      CYP2J3, CYP4A1/2/3, and CYP4Fs in the heart, lung, kidney, and liver were
      determined by Western blot analysis. The levels of AA metabolites were determined
      by liquid chromatography-electrospray ionization mass spectroscopy. This was
      followed by determination of regioselectivity, immunoinhibition effect, and the
      kinetic profile of AA metabolism. AA was metabolized to epoxyeicosatrienoic acids
      and 19- and 20-hydroxyeicosatetraenoic acid in the heart, lung, kidney, and liver
      but with varying metabolic activities and regioselectivity. Anti-P450 antibodies
      were found to differentially inhibit AA epoxygenation and hydroxylation in these
      organs. Our data suggest that the predominant epoxygenases are CYP2C11, CYP2B1,
      CYP2C23, and CYP2C11/CYP2C23 for the heart, lung, kidney, and liver,
      respectively. On the other hand, CYP4A1 is the major omega-hydroxylase in the
      heart and kidney; whereas CYP4A2 and/or CYP4F1/4 are probably the major
      hydroxlases in the lung and liver. These results provide important insights into
      the activities of P450 epoxygenases and P450 hydroxylases-mediated AA metabolism
      in different organs and their associated P450 protein levels.

PMID- 23139021
TI  - Guided Internet-delivered cognitive behavioural therapy for chronic pain patients
      who have residual symptoms after rehabilitation treatment: randomized controlled
      trial.
AB  - BACKGROUND: Chronic pain can be treated with cognitive behavioural therapy
      delivered in multidisciplinary settings. However, relapse is likely, and there is
      a need for cost-effective secondary interventions for persons with residual
      problems after rehabilitation. The aim of the present study was to investigate
      the effects of a guided Internet-delivered cognitive behavioural intervention for
      patients who had completed multidisciplinary treatment at a pain management unit.
      METHODS: A total of 72 persons with residual pain problems were included in the
      study and were randomized to either treatment for 8 weeks or to a control group
      who were invited to participate in a moderated online discussion forum. The
      participants had different chronic pain conditions, and a majority were women
      (72%). Twenty-two percent of the participants dropped out of the study before the
      post-treatment assessment. RESULTS: Intent-to-treat analyses demonstrated
      differences on the catastrophizing subscale of the Coping Strategies
      Questionnaire (Cohen's d = 0.70), in favour of the treatment group but a small
      within-group effect. Differences were also found on other measures of pain
      related distress, anxiety and depressive symptoms. A 6-month follow-up exhibited
      maintenance of improvements. CONCLUSIONS: We conclude that Internet-delivered
      treatment can be partly effective for persons with residual problems after
      completed pain rehabilitation.

PMID- 23139022
TI  - Identification of small molecules that interfere with H1N1 influenza A viral
      replication.
AB  - Successful replication of the influenza A virus requires both viral proteins and
      host cellular factors. In this study we used a cellular assay to screen for small
      molecules capable of interfering with any of such necessary viral or cellular
      components. We used an established reporter assay to assess influenza viral
      replication by monitoring the activity of co-expressed luciferase. We screened a
      diverse chemical compound library, resulting in the identification of compound 7,
      which inhibits a novel yet elusive target. Quantitative real-time PCR studies
      confirmed the dose-dependent inhibitory activity of compound 7 in a viral
      replication assay. Furthermore, we showed that compound 7 is effective in
      rescuing high-dose influenza infection in an in vivo mouse model. As oseltamivir
      resistant influenza strains emerge, compound 7 could be further investigated as a
      new and potentially suitable scaffold for the development of anti-influenza
      agents that act on novel targets.

PMID- 23139023
TI  - Statistical analysis of mixed recurrent event data with application to cancer
      survivor study.
AB  - Event history studies occur in many fields including economics, medical studies,
      and social science. In such studies concerning some recurrent events, two types
      of data have been extensively discussed in the literature. One is recurrent event
      data that arise if study subjects are monitored or observed continuously. In this
      case, the observed information provides the times of all occurrences of the
      recurrent events of interest. The other is panel count data, which occur if the
      subjects are monitored or observed only periodically. This can happen if the
      continuous observation is too expensive or not practical, and in this case, only
      the numbers of occurrences of the events between subsequent observation times are
      available. In this paper, we discuss a third type of data, which is a mixture of
      recurrent event and panel count data and for which there exists little
      literature. For regression analysis of such data, we present a marginal mean
      model and propose an estimating equation-based approach for estimation of
      regression parameters. We conduct a simulation study to assess the finite sample
      performance of the proposed methodology, and the results indicate that it works
      well for practical situations. Finally, we apply it to a motivating study on
      childhood cancer survivors.

PMID- 23139024
TI  - Cardioprotection by acetylcholine: a novel mechanism via mitochondrial biogenesis
      and function involving the PGC-1alpha pathway.
AB  - Mitochondrial biogenesis disorders appear to play an essential role in cardiac
      dysfunction. Acetylcholine as a potential pharmacologic agent exerts
      cardioprotective effects. However, its direct action on mitochondria biogenesis
      in acute cardiac damage due to ischemia/reperfusion remains unclear. The present
      study determined the involvement of mitochondrial biogenesis and function in the
      cardiopotection of acetylcholine in H9c2 cells subjected to hypoxia/reoxygenation
      (H/R). Our findings demonstrated that acetylcholine treatment on the beginning of
      reoxygenation improved cell viability in a concentration-dependent way.
      Consequently, acetylcholine inhibited the mitochondrial morphological
      abnormalities and caused a significant increase in mitochondrial density, mass,
      and mitochondrial DNA (mtDNA) copy number. Accordingly, acetylcholine enhanced
      ATP synthesis, membrane potentials, and activities of mitochondrial complexes in
      contrast to H/R alone. Furthermore, acetylcholine stimulated the transcriptional
      activation and protein expression of peroxisome proliferator-activated receptor
      co-activator 1 alpha (PGC-1alpha, the central factor for mitochondrial
      biogenesis) and its downstream targets including nuclear respiration factors and
      mitochondrial transcription factor A. In addition, acetylcholine activated
      phosphorylation of AMP-activated protein kinase (AMPK), which was located
      upstream of PGC-1alpha. Atropine (muscarinic receptor antagonist) abolished the
      favorable effects of acetylcholine on mitochondria. Knockdown of PGC-1alpha or
      AMPK by siRNA blocked acetylcholine-induced stimulating effects on mtDNA copy
      number and against cell injury. In conclusion, we suggested, acetylcholine as a
      mitochondrial nutrient, protected against the deficient mitochondrial biogenesis
      and function induced by H/R injury in a cellular model through muscarinic
      receptor-mediated, AMPK/PGC-1alpha-associated regulatory program, which may be of
      significance in elucidating a novel mechanism underlying acetylcholine-induced
      cardioprotection.

PMID- 23139025
TI  - [New treatment strategies for male lower urinary tract symptoms].
AB  - For patients with lower urinary tract symptoms (LUTS), alpha1-adrenoreceptor
      inhibitors and 5-alpha reductase inhibitors as well as their combination are
      considered the gold standard. In addition, anticholinergic agents are being
      introduced as monotherapy or in combination with alpha1-adrenocepetor inhibitors
      for patients with predominant storage disorders. Phosphodiesterase 5 (PDE5)
      inhibitors are often the best option for patients with LUTS who also suffer from
      erectile dysfunction. Recently, novel treatment options have been presented and
      intraprostatic injection of various agents, such as botulinum toxin A, NX-1207
      and PRX302 has shown promising initial results. In addition, innovative minimally
      invasive treatment options, such as UroLift(r) appear to be efficacious and safe
      in this patient cohort. Particular emphasis should be laid on patients with LUTS
      and concomitant sexual disorders.

PMID- 23139027
TI  - [Unconventional treatment methods in urology].

PMID- 23139026
TI  - [Irreversible electroporation: the new generation of local ablation techniques
      for renal cell carcinoma].
AB  - BACKGROUND: Local ablation techniques are a major focus of current developments
      in oncology. The primary aim is to retain organs and preserve organ functions
      without compromising the oncological outcome. METHOD: Irreversible
      electroporation (IRE) is a novel ablation technique that involves the application
      of high-voltage pulses to induce cell apoptosis without causing thermal damage to
      the target tissue or adjacent structures. AIM: First published in 2005 IRE is
      currently undergoing preclinical and clinical trials in several areas of oncology
      and the initial results have been promising. The IRE technique could be a
      significant development in ablation treatment for renal cell carcinoma (RCC) but
      decisive proof of its effectiveness for local RCC has not yet been provided. This
      study presents the results of preclinical and initial clinical trials which are
      discussed and compared with those of other ablation techniques in order to
      demonstrate the current value of IRE.

PMID- 23139028
TI  - Symptoms of shrinking lung syndrome reveal systemic lupus erythematosus in a 12
      year-old girl.
AB  - While pleuropulmonary involvement in systemic lupus erythematosus (SLE) is a
      common occurrence, shrinking lung syndrome (SLS) is a rare complication of SLE,
      particularly in children. We report on a teenager girl with a primary SLE
      diagnosis, which was based upon clinical, imaging, lung-function and histological
      findings ascertained to be compatible with SLS. Following a pneumonia, the
      patient developed inflammatory residues in the lower lobes, an event that
      probably caused diaphragmatic immobility and subsequently led to SLS. Treatment
      response to steroids, cyclophosphamide and hydroxychloroquine in this case was
      excellent, and efficacy was more profound than previously has been reported in
      the literature with respect to pediatric patients. This case report argues that
      prognosis of SLS in SLE is likely to be favorable when the diagnosis is made
      early and the disease is treated appropriately.

PMID- 23139029
TI  - Promoting volunteerism in global health: lessons from a medical mission in
      northern Mexico.
AB  - The challenges of meeting global health care needs in communities throughout the
      developing world are becoming increasingly complex. Understanding what motivates
      volunteers is important for organizations that seek to harness and develop long
      term volunteers in order to meet the need for global health care services. Here
      we report a case study of a successful volunteer clinic that has provided
      medical, dental and surgical services to under-served residents of northern
      Mexico for more than 20 years. Our objective was to understand what promotes
      sustained volunteerism. Thirty semi-structured interviews were conducted with
      students, residents, nurses, dentists, oral surgeons and community volunteers, in
      addition to four full days of participant observation. We analysed volunteers'
      experiences with a real-life global medical mission and offer recommendations.
      Motivating factors included psychological and emotional rewards, career-related
      benefits, opportunities for interpersonal interaction, the opportunity to serve
      disadvantaged communities and personal relevance of the mission. We demonstrate
      the paramount importance of volunteer-patient interaction, having a dedicated
      facilitator to recruit and pave the way for first-time volunteers and the value
      of using multiple recruitment strategies. Most important, we show that
      organizations must focus on facilitating first-time volunteers' experiences,
      particularly by ensuring that they are given specific roles and responsibilities,
      one of the best predictors of volunteer satisfaction and sustained volunteerism.

PMID- 23139030
TI  - Long-term outcomes of unilateral orbital fat decompression for thyroid eye
      disease.
AB  - BACKGROUND: The aim of this study was to evaluate the long-term outcomes after
      unilateral orbital fat decompression in patients with thyroid eye disease.
      DESIGN: Retrospective, comparative, cross-sectional study PARTICIPANTS: Thirty
      three orbits of 33 patients were included in this study. Of the 33 patients, 13
      underwent fat decompression (group A), and the other 20 had bony decompression
      (group B). METHODS: The medical records of patients who underwent orbital
      decompression to reduce proptosis for thyroid eye disease were retrospectively
      reviewed. The degrees of proptosis were measured by Hertel exophthalmometry
      preoperatively and over a follow-up period of more than 3 years. We evaluated the
      change in proptosis after surgery. MAIN OUTCOME MEASURES: Postoperative change in
      exophthalmos. RESULTS: A recurrence in proptosis from fat decompression was seen
      in ten patients (76.9 %) in group A and in only two patients (10 %) in group B.
      The amount of regression due to surgery after 3 years was 2.3 +/- 1.4 mm and 0.7
      +/- 0.9 mm in groups A and B respectively. The tendency of regression was more
      prominent in group A than in group B. CONCLUSION: The long-term effect of
      unilateral orbital fat decompression for the reduction of proptosis in patients
      with thyroid eye disease may be weak, leading to regression. Care should be taken
      when determining the extent of fat decompression with consideration for this
      tendency.

PMID- 23139031
TI  - Endoscopic ultrasound (EUS)-guided ethanol injection for hepatocellular carcinoma
      difficult to treat with percutaneous local treatment.

PMID- 23139032
TI  - Varicella zoster gastritis in an immunocompetent adult woman.

PMID- 23139033
TI  - Acute necrotizing pancreatitis, gastric ischemia, and portal venous gas
      complicating intragastric balloon placement.

PMID- 23139034
TI  - Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) of the right
      adrenal gland.

PMID- 23139035
TI  - Rectal tonsil associated with Epstein-Barr virus.

PMID- 23139036
TI  - Development of subsquamous cancer after hybrid endoscopic therapy for
      intramucosal Barrett's cancer.

PMID- 23139037
TI  - Development of esophageal adenocarcinoma on buried glands following
      radiofrequency ablation for Barrett's esophagus.

PMID- 23139038
TI  - Late diagnosis of Henoch-Schonlein purpura following detection of jejunal
      ischemia on conventional endoscopy.

PMID- 23139039
TI  - A new large-diameter overtube for endoscopic submucosal dissection in the colon.

PMID- 23139040
TI  - A case of perforation following endoscopic biopsy of advanced gastric cancer.

PMID- 23139041
TI  - Endoscopic submucosal dissection using the endoscopic operation robot.

PMID- 23139043
TI  - Parallel acoustic delay lines for photoacoustic tomography.
AB  - Achieving real-time photoacoustic (PA) tomography typically requires multi
      element ultrasound transducer arrays and their associated multiple data
      acquisition (DAQ) electronics to receive PA waves simultaneously. We report the
      first demonstration of a photoacoustic tomography (PAT) system using optical
      fiber-based parallel acoustic delay lines (PADLs). By employing PADLs to
      introduce specific time delays, the PA signals (on the order of a few micro
      seconds) can be forced to arrive at the ultrasonic transducers at different
      times. As a result, time-delayed PA signals in multiple channels can be
      ultimately received and processed in a serial manner with a single-element
      transducer, followed by single-channel DAQ electronics. Our results show that an
      optically absorbing target in an optically scattering medium can be
      photoacoustically imaged using the newly developed PADL-based PAT system.
      Potentially, this approach could be adopted to significantly reduce the
      complexity and cost of ultrasonic array receiver systems.

PMID- 23139044
TI  - Test-retest assessment of cortical activation induced by repetitive transcranial
      magnetic stimulation with brain atlas-guided optical topography.
AB  - Repetitive transcranial magnetic stimulation (rTMS) is a technology that
      stimulates neurons with rapidly changing magnetic pulses with demonstrated
      therapeutic applications for various neuropsychiatric disorders. Functional near
      infrared spectroscopy (fNIRS) is a suitable tool to assess rTMS-evoked brain
      responses without interference from the magnetic or electric fields generated by
      the TMS coil. We have previously reported a channel-wise study of combined
      rTMS/fNIRS on the motor and prefrontal cortices, showing a robust decrease of
      oxygenated hemoglobin concentration (Delta[HbO2]) at the sites of 1-Hz rTMS and
      the contralateral brain regions. However, the reliability of this putative
      clinical tool is unknown. In this study, we develop a rapid optical topography
      approach to spatially characterize the rTMS-evoked hemodynamic responses on a
      standard brain atlas. A hemispherical approximation of the brain is employed to
      convert the three-dimensional topography on the complex brain surface to a two
      dimensional topography in the spherical coordinate system. The test-retest
      reliability of the combined rTMS/fNIRS is assessed using repeated measurements
      performed two to three days apart. The results demonstrate that the Delta[HbO2]
      amplitudes have moderate-to-high reliability at the group level; and the spatial
      patterns of the topographic images have high reproducibility in size and a
      moderate degree of overlap at the individual level.

PMID- 23139045
TI  - Concerted spatial-frequency and polarization-phase filtering of laser images of
      polycrystalline networks of blood plasma smears.
AB  - The complex technique of concerted polarization-phase and spatial-frequency
      filtering of blood plasma laser images is suggested. The possibility of obtaining
      the coordinate distributions of phases of linearly and circularly birefringent
      protein networks of blood plasma separately is presented. The statistical
      (moments of the first to fourth orders) and scale self-similar (logarithmic
      dependences of power spectra) structure of phase maps of different types of
      birefringence of blood plasma of two groups of patients--healthy people (donors)
      and those suffering from rectal cancer--is investigated. The diagnostically
      sensitive parameters of a pathological change of the birefringence of blood
      plasma polycrystalline networks are determined. The effectiveness of this
      technique for detecting change in birefringence in the smears of other biological
      fluids in diagnosing the appearance of cholelithiasis (bile), operative
      differentiation of the acute and gangrenous appendicitis (exudate), and
      differentiation of inflammatory diseases of joints (synovial fluid) is shown.

PMID- 23139042
TI  - Clinical and laboratory aspects of the diagnosis and management of cutaneous and
      subcutaneous infections caused by rapidly growing mycobacteria.
AB  - Rapidly growing mycobacteria (RGM) are known to cause pulmonary, extra-pulmonary,
      systemic/disseminated, and cutaneous and subcutaneous infections. The erroneous
      detection of RGM that is based solely on microscopy, solid and liquid cultures,
      Bactec systems, and species-specific polymerase chain reaction (PCR) may produce
      misleading results. Thus, inappropriate therapeutic measures may be used in
      dermatologic settings, leading to increased numbers of skin deformity cases or
      recurrent infections. Molecular tools such as the sequence analyses of 16S rRNA,
      rpoB and hsp65 or PCR restriction enzyme analyses, and the alternate gene
      sequencing of the superoxide dismutase (SOD) gene, dnaJ, the 16S-23S rRNA
      internal transcribed spacers (ITS), secA, recA1, dnaK, and the 32-kDa protein
      gene have shown promising results in the detection of RGM species. PCR
      restriction enzyme analyses (PRA) work better than conventional methods at
      identifying species that are closely related. Recently introduced molecular tools
      such as matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF MS), pyrosequencing, DNA chip technology, and Beacon
      probes-combined PCR probes have shown comparable results in the detection of
      various species of RGM. Closely related RGM species (e.g., Mycobacterium
      fortuitum, M. chelonae, and M. abscessus) must be clearly differentiated using
      accurate molecular techniques because their therapeutic responses are species
      specific. Hence, this paper reviews the following aspects of RGM: (i) its
      sources, predisposing factors, clinical manifestations, and concomitant fungal
      infections; (ii) the risks of misdiagnoses in the management of RGM infections in
      dermatological settings; (iii) the diagnoses and outcomes of treatment responses
      in common and uncommon infections in immunocompromised and immunocompetent
      patients; (iv) conventional versus current molecular methods for the detection of
      RGM; (v) the basic principles of a promising MALDI-TOF MS, sampling protocol for
      cutaneous or subcutaneous lesions and its potential for the precise
      differentiation of M. fortuitum, M. chelonae, and M. abscessus; and (vi)
      improvements in RGM infection management as described in the recent 2011 Clinical
      and Laboratory Standards Institute (CLSI) guidelines, including interpretation
      criteria of molecular methods and antimicrobial drug panels and their break
      points [minimum inhibitory concentrations (MICs)], which have been highlighted
      for the initiation of antimicrobial therapy.

PMID- 23139047
TI  - Pulmonary adenofibroma in a middle-aged man: report of a case.
AB  - We report a case of pulmonary adenofibroma, a rare benign soft-tissue tumor
      characterized by a combination of glandular and spindle stromal elements, in a 55
      year-old man. This case is interesting because of the unusual X-ray and computed
      tomography (CT) imaging findings of a well-defined, subpleural soft-tissue nodule
      in the inferior lobe of the left lung, which showed no enhancement after contrast
      scan. The tumor was resected completely via video-assisted thoracoscopy.
      Microscopic and immunohistochemical examinations supported the diagnosis of a
      benign pulmonary adenofibroma. The patient remains well with no evidence of
      recurrence 16 months after surgery. Although the imaging findings were
      nonspecific, adenofibroma may be one of diagnostic inclusions of soft-tissue
      nodules of the lung in middle-aged patients.

PMID- 23139048
TI  - Intersphincteric resection for very low rectal cancer: a systematic review.
AB  - Radical surgical treatment for very low rectal cancer near the anus has generally
      involved abdominoperineal resection. Various sphincter-saving operations have
      been developed for such tumors to optimize the patients' postoperative quality of
      life. Current protocols focus on intersphincteric resection (ISR), which differs
      from conventional hand-sewn coloanal anastomosis (CAA) after low anterior
      resection. However, the efficacy of ISR remains unclear. The surgical, oncologic,
      and functional outcomes after intersphincteric resection (ISR) were reviewed.
      This review of the current literature was conducted by searching the PubMed
      online database. Articles focusing specifically on conventional hand-sewn CAA
      were excluded from this study. The mean mortality rate is <2 %, and the mean
      morbidity rate ranges from 7.7 to 38.3 %. The mean local recurrence rate varies
      widely from 0 to 22.7 %, with a mean follow-up duration of 40-94 months. The mean
      disease-free and overall 5-year survival rates are 69-86 and 79-97 months,
      respectively. Functional outcomes are generally acceptable, but accurate
      evaluation is extremely difficult due to the absence of unified appraisal
      methods. ISR appears surgically, oncologically and functionally acceptable.
      However, more experience and better understanding of the oncology, anal
      physiology, and pelvic anatomy are necessary to achieve successful outcomes
      without complications, and to improve patient survival.

PMID- 23139046
TI  - Structure and function of the SPRY/B30.2 domain proteins involved in innate
      immunity.
AB  - The SPRY domain is a protein interaction module found in 77 murine and ~100 human
      proteins, and is implicated in important biological pathways, including those
      that regulate innate and adaptive immunity. The current definition of the SPRY
      domain is based on a sequence repeat discovered in the splA kinase and ryanodine
      receptors. The greater SPRY family is divided into the B30.2 (which contains a
      PRY extension at the N-terminus) and "SPRY-only" sub-families. In this brief
      review, we examine the current structural and biochemical literature on
      SPRY/B30.2 domain involvement in key immune processes and highlight a PRY-like 60
      amino acid region in the N-terminus of "SPRY-only" proteins. Phylogenetic,
      structural, and functional analyses suggest that this N-terminal region is
      related to the PRY region of B30.2 and should be characterized as part of an
      extended SPRY domain. Greater understanding of the functional importance of the N
      terminal region in "SPRY only" proteins will enhance our ability to interrogate
      SPRY interactions with their respective binding partners.

PMID- 23139049
TI  - Feasibility and potential benefit of preoperative chemotherapy for colorectal
      liver metastasis (CLM): a single-centered retrospective study.
AB  - PURPOSES: The benefit of neo-adjuvant chemotherapy for liver-limited metastatic
      colorectal cancer is still controversial. This study defined the resectability
      regardless of the size and number of liver metastases, and attempted curative
      hepatic resection in all cases. METHODS: Sixty-four patients that tolerated
      chemotherapy were diagnosed with CLM (colorectal liver metastases) without
      extrahepatic metastase from January 2007 to November 2010, and received an
      oxaliplatin-based regimen. This study assessed the resectability after
      chemotherapy, and the patients were divided in two groups; the resected and
      unresected group. Sixteen patients underwent hepatic resection without
      chemotherapy. RESULTS: Thirty-five patients underwent surgical resection
      (resected group) and twenty-nine patients were considered unresectable
      (unresected group). All 35 patients in the resected group safely received
      oxaliplatin-based chemotherapy safely without serious adverse effects. No serious
      postoperative complications were observed. The median overall survival (MST) was
      significantly higher in the resected than in the unresected group (56.93 [95% CI
      38.13-75.73] and 25.07 months [95% CI 17.87-32.26], respectively; P < 0.001). The
      median disease-free survival was 20.2 [95% CI 8.82-31.65] months in the resected
      group. CONCLUSION: Preoperative chemotherapy for CLM is well tolerated and does
      not increase postoperative complications. Curative surgery with preoperative
      chemotherapy has the potential to improve the overall survival in patients with
      CLM.

PMID- 23139050
TI  - Chiral sulfoxides in the enantioselective allylation of aldehydes with
      allyltrichlorosilane: a kinetic study.
AB  - The mechanism of the allylation of aldehydes in the presence of
      allyltrichlorosilane employing the commercially available (R)-methyl p-tolyl
      sulfoxide as a Lewis base has been investigated. The combination of kinetic
      measurements, conductivity analysis and quantum chemical calculations indicates
      that the reaction proceeds through a dissociative pathway in which an octahedral
      cationic complex with two sulfoxides is involved. The lack of turnover is
      ascribed to the formation of neutral sulfurane derivatives.

PMID- 23139051
TI  - Low back pain-related beliefs and likely practice behaviours among final-year
      cross-discipline health students.
AB  - BACKGROUND: Evidence points to clinicians' beliefs and practice behaviours
      related to low back pain (LBP), which are discordant with contemporary evidence.
      While interventions to align beliefs and behaviours with evidence among
      clinicians have demonstrated effectiveness, a more sustainable and cost-effective
      approach to positively developing workforce capacity in this area may be to
      target the emerging workforce. The aim of this study was to investigate beliefs
      and clinical recommendations for LBP, and their alignment to evidence, in
      Australian university allied health and medical students. METHODS: Final-year
      students in chiropractic, medicine, occupational therapy, pharmacy and
      physiotherapy disciplines in three Western Australian universities responded to a
      survey. Demographic data, LBP-related beliefs data [modified Health Care
      Providers Pain and Impact Relationship Scale (HC-PAIRS) and the Back Pain Beliefs
      Questionnaire (BBQ)] and activity, rest and work clinical recommendations for an
      acute LBP clinical vignette were collected. RESULTS: Six hundred two students
      completed the survey (response rate 74.6%). Cross-discipline differences in
      beliefs and clinical recommendations were observed (p > 0.001). Physiotherapy and
      chiropractic students reported significantly more helpful beliefs compared with
      the other disciplines, while pharmacy students reported the least helpful
      beliefs. A greater proportion of chiropractic and physiotherapy students reported
      guideline-consistent recommendations compared with other disciplines. HC-PAIRS
      and BBQ scores were strongly associated with clinical recommendations,
      independent to the discipline of study and prior experience of LBP. CONCLUSIONS:
      Aligning cross-discipline university curricula with current evidence may provide
      an opportunity to facilitate translation of this evidence into practice with a
      focus on a consistent, cross-discipline approach to LBP management.

PMID- 23139052
TI  - Synergistic effect of scavenger receptor A and low-density lipoprotein receptor
      on macrophage foam cell formation under inflammatory stress.
AB  - To provide experimental evidence for the effect of inflammation on cholesterol
      accumulation in macrophages, we investigated the expression of low-density
      lipoprotein receptor (LDL-R) and scavenger receptor A (SR-A) genes and proteins
      in the lipopolysaccharide (LPS)-stimulated macrophage-like RAW264.7 cell line.
      RAW264.7 cells were incubated in serum-free medium in the absence or presence of
      LDL alone, LDL+LPS and LPS alone. Intracellular cholesterol content, tumor
      necrosis factor alpha levels in the supernatants, mRNA and protein expression of
      LDL-R and SR-A in the treated cells were assessed by Oil Red O staining
      cholesterol enzymatic assay, enzyme-linked immunosorbent assay, semi-quantitative
      polymerase chain reaction and western blot analysis, respectively. Our results
      demonstrated that LPS was able to upregulate SR-A mRNA and protein expression,
      override LDL-R suppression induced by a high dose of LDL and increase LDL uptake
      by enhancing receptor expression, leading to foam cell formation in RAW264.7
      cells. These findings suggest that the synergy of the upregulation of SR-A and
      dysregulation of LDL-R under inflammatory stress may contribute to macrophage
      derived foam cell formation.

PMID- 23139053
TI  - High-performance NO2 sensors based on chemically modified graphene.
AB  - Covalently grafting reduced graphene oxide (rGO) sheets with sulfophenyl or
      ethylenediamine groups can produce chemically modified graphene (CMG) for
      fabricating high-performance gas sensors. The NO(2) sensors based on these CMGs
      exhibit sensitivities 4 to 16 times higher than that of a sensor based on rGO.
      They also show excellent selectivity and repeatability without the aid of UV
      light or thermal treatment.

PMID- 23139054
TI  - Gender-specific elimination of continuous-infusional 5-fluorouracil in patients
      with gastrointestinal malignancies: results from a prospective population
      pharmacokinetic study.
AB  - BACKGROUND: This study was initiated to assess the quantitative impact of patient
      anthropometrics and dihydropyrimidine dehydrogenase (DPYD) mutations on the
      pharmacokinetics (PK) of 5-fluorouracil (5FU) and to explore limited sampling
      strategies of 5FU. PATIENTS AND METHODS: We included 32 patients with
      gastrointestinal malignancies, receiving 46-h continuous-infusional 5FU and
      performed PK-sampling at baseline, 15, 30, 45 min, 1 and 2 h after the start of
      infusion and at the end of infusion, for 2 subsequent cycles. Plasma
      concentrations of 5FU, 5-fluorodihydrouracil (5FUH2), uracil (U) and 5,6
      dihydrouracil (UH2) were determined using LC-MS/MS and submitted to population PK
      analysis using nonlinear mixed-effects modeling. Broad genotyping of DPYD was
      performed, and the potential impact of the DPYD genotype on the elimination of
      5FU was assessed. Limited sampling strategies were evaluated for their accuracy
      to predict steady-state concentrations of 5FU (CSS(5FU)), using data simulations
      based on the final PK-model. RESULTS: The area-under-the concentration-time curve
      of 5FU (AUC(5FU)) was found to be <20 mg h/L in 33 occasions (58 %), between 20
      and 30 mg h/L in 17 occasions (30 %) and >30 mg h/L in 7 occasions (12 %). Men
      had a 26 % higher elimination of 5FU and a 18 % higher apparent elimination of
      5FUH2. Accordingly, women had a higher AUC(5FU) compared to men (22 vs. 18 mg
      h/L, p = 0.04). No DPYD risk variants were found, and the DPYD variants detected
      (c.496A>G, c.1601G>A, c.1627A>G) were not significantly associated with the
      elimination of 5FU. Individual baseline UH(2)/U ratio was significantly
      associated with AUC(5FU) (R = -0.49, p < 0.001). Limited sampling strategies with
      time-points <3 h after the start of infusion were not adequate to predict
      CSS(5FU). Female gender was the only predictor of nausea/emesis in the
      multivariate model. CONCLUSIONS: Gender-specific elimination of 5FU is supported
      by the present data and may partly explain the gender-specific association
      between DPYD risk variants and 5FU-specific toxicity.

PMID- 23139055
TI  - Use of antidepressants and the risk of breast cancer: a meta-analysis.
AB  - The goal of this study was to perform a meta-analysis to examine the association
      between the use of antidepressants (AD) and the risk of breast cancer. We
      searched the EMBASE and MEDLINE databases from inception through February 25,
      2012, using search terms related to ADs and breast cancer. Two evaluators
      independently reviewed and selected articles and extracted data based on
      predetermined selection criteria. Pooled effect estimates were obtained by using
      random- and fixed effects meta-analyses. Of the 3,209 titles identified, 18
      articles met the inclusion criteria. The overall risk of breast cancer did not
      increase among AD users [adjusted odds ratio (aOR) 1.02; 95 % CI 0.96-1.08].
      Those who took tricyclic antidepressants (TCAs) or selective serotonin reuptake
      inhibitors (SSRIs) were not at increased risks of breast cancer. In subgroup meta
      analyses, null associations were consistent across the type of AD, funding
      sources, the number of adjusted variables, medication dose, the ascertainment of
      exposure, and methodological quality. In subgroup analyses based on exposure
      duration, a marginal association was observed for the use of SSRIs < 1-2 years
      (aOR 1.10; 95 % CI 1.02-1.19). However, this effect was attenuated over time and
      those using SSRIs for more than 1-2 years had no elevated breast cancer risk.
      These results support the lack of a clinically meaningful association between AD
      use and the development of breast cancer and provide considerable reassurance.
      Given that the data collected to date do not support changing the current
      prescribing patterns for ADs, the important benefits of AD therapy must be
      considered.

PMID- 23139058
TI  - Exercise for health: a randomized, controlled trial evaluating the impact of a
      pragmatic, translational exercise intervention on the quality of life, function
      and treatment-related side effects following breast cancer.
AB  - Exercise for Health was a randomized, controlled trial designed to evaluate two
      modes of delivering (face-to-face [FtF] and over-the-telephone [Tel]) an 8-month
      translational exercise intervention, commencing 6-weeks post-breast cancer
      surgery (PS). Outcomes included quality of life (QoL), function (fitness and
      upper body) and treatment-related side effects (fatigue, lymphoedema, body mass
      index, menopausal symptoms, anxiety, depression and pain). Generalised estimating
      equation modelling determined time (baseline [5 weeks PS], mid-intervention [6
      months PS], post-intervention [12 months PS]), group (FtF, Tel, Usual Care [UC])
      and time-by-group effects. 194 women representative of the breast cancer
      population were randomised to the FtF (n = 67), Tel (n = 67) and UC (n = 60)
      groups. There were significant (p < 0.05) interaction effects on QoL, fitness and
      fatigue with differences being observed between the treatment groups and the UC
      group. Trends observed for the treatment groups were similar. The treatment
      groups reported improved QoL, fitness and fatigue over time and changes observed
      between baseline and post-intervention were clinically relevant. In contrast, the
      UC group experienced no change, or worsening QoL, fitness and fatigue, mid
      intervention. Although improvements in the UC group occurred by 12-months post
      surgery, the change did not meet the clinically relevant threshold. There were no
      differences in other treatment-related side effects between groups. This
      translational intervention trial, delivered either FtF or Tel, supports exercise
      as a form of adjuvant breast cancer therapy that can prevent declines in fitness
      and function during treatment and optimise recovery post-treatment.

PMID- 23139059
TI  - The importance of human cardiac anatomy for translational research.

PMID- 23139060
TI  - Adaptation to climate change of dioecious plants: does gender balance matter?

PMID- 23139057
TI  - Patterns and predictors of breast cancer chemotherapy use in Kaiser Permanente
      Northern California, 2004-2007.
AB  - Chemotherapy regimens for early stage breast cancer have been tested by
      randomized clinical trials, and specified by evidence-based practice guidelines.
      However, little is known about the translation of trial results and guidelines to
      clinical practice. We extracted individual-level data on chemotherapy
      administration from the electronic medical records of Kaiser Permanente Northern
      California (KPNC), a pre-paid integrated healthcare system serving 29 % of the
      local population. We linked data to the California Cancer Registry, incorporating
      socio-demographic and tumor factors, and performed multivariable logistic
      regression analyses on the receipt of specific chemotherapy regimens. We
      identified 6,004 women diagnosed with Stage I-III breast cancer at KPNC during
      2004-2007; 2,669 (44.5 %) received at least one chemotherapy infusion at KPNC
      within 12 months of diagnosis. Factors associated with receiving chemotherapy
      included <50 years of age [odds ratio (OR) 2.27, 95 % confidence interval (CI)
      1.81-2.86], tumor >2 cm (OR 2.14, 95 % CI 1.75-2.61), involved lymph nodes (OR
      11.3, 95 % CI 9.29-13.6), hormone receptor-negative (OR 6.94, 95 % CI 4.89-9.86),
      Her2/neu-positive (OR 2.71, 95 % CI 2.10-3.51), or high grade (OR 3.53, 95 % CI
      2.77-4.49) tumors; comorbidities associated inversely with chemotherapy use
      [heart disease for anthracyclines (OR 0.24, 95 % CI 0.14-0.41), neuropathy for
      taxanes (OR 0.45, 95 % CI 0.22-0.89)]. Relative to high-socioeconomic status
      (SES) non-Hispanic Whites, we observed less anthracycline and taxane use by SES
      non-Hispanic Whites (OR 0.63, 95 % CI 0.49-0.82) and American Indians (OR 0.23,
      95 % CI 0.06-0.93), and more anthracycline use by high-SES Asians/Pacific
      Islanders (OR 1.72, 95 % CI 1.02-2.90). In this equal-access healthcare system,
      chemotherapy use followed practice guidelines, but varied by race and socio
      demographic factors. These findings may inform efforts to optimize quality in
      breast cancer care.

PMID- 23139061
TI  - Hierarchical porous materials: catalytic applications.
AB  - In this review, we discuss the phenomenon of complementary macropore
      incorporation into mesoporous and/or microporous solids in order to enhance their
      catalytic performance in fuels and chemicals synthesis.

PMID- 23139063
TI  - [Intracerebral haemorrhage: no decrease of incidence in sight].

PMID- 23139062
TI  - Surgical resection for non-small cell lung cancer: clinical features and outcomes
      for a consecutive series at an Irish tertiary referral centre.
AB  - BACKGROUND: Few patients diagnosed with lung cancer are still alive 5 years after
      diagnosis. The aim of the current study was to conduct a 10-year review of a
      consecutive series of patients undergoing curative-intent surgical resection at
      the largest tertiary referral centre to identify prognostic factors. METHODS:
      Case records of all patients operated on for lung cancer between 1998 and 2008
      were reviewed. The clinical features and outcomes of all patients with non-small
      cell lung cancer (NSCLC) stage I-IV were recorded. RESULTS: A total of 654
      patients underwent surgical resection with curative intent during the study
      period. Median overall survival for the entire cohort was 37 months. The median
      age at operation was 66 years, with males accounting for 62.7 %. Squamous cell
      type was the most common histological subtype, and lobectomies were performed in
      76.5 % of surgical resections. Pneumonectomy rates decreased significantly in the
      latter half of the study (25 vs. 16.3 %), while sub-anatomical resection more
      than doubled (2 vs. 5 %) (p < 0.005). Clinico-pathological characteristics
      associated with improved survival by univariate analysis include younger age,
      female sex, smaller tumour size, smoking status, lobectomy, lower T and N status
      and less advanced pathological stage. Age, gender, smoking status and tumour
      size, as well as T and N descriptors have emerged as independent prognostic
      factors by multivariate analysis. CONCLUSION: We identified several factors that
      predicted outcome for NSCLC patients undergoing curative-intent surgical
      resection. Survival rates in our series are comparable to those reported from
      other thoracic surgery centres.

PMID- 23139064
TI  - [Cerebral amyloid angiopathy--an update].
AB  - Cerebral amyloid angiopathy (CAA) belongs to the group of amyloidoses and is
      characterised by the deposition and accumulation of beta-amyloid (Abeta) in small
      arterial vessels of the brain. Hereditary forms of CAA exist but sporadic CAA is
      much more frequent. Deposition of Abeta induces degenerative changes of the
      cerebral vascular system (thickening of the vessel wall, constriction of vascular
      lumen, microaneurysms, dissection) that trigger the development of the typical
      clinical presentation of CAA, that is spontaneous intracerebral haemorrhage.
      Apart from haemorrhages, also cerebral ischaemia, transient neurological
      symptoms, leukencephalopathy as well as cognitive decline and dementia can occur
      in association with CAA. The definite diagnosis of CAA is only possible by means
      of pathological examination, even though neuroimaging and clinical findings allow
      the diagnosis of a probable CAA. Currently, no specific causal therapy exists.
      Although CAA is located in the range of neurological diseases psychiatric
      symptoms might occur. In the review, we discuss epidemiological, pathogenetic,
      clinical and diagnostic aspects and possible psychiatric implications of CAA.

PMID- 23139065
TI  - [Can cannabis use increase the risk for schizophrenic psychoses?].
AB  - BACKGROUND: In recent years, cannabis has been increasingly discussed as one of
      the most important environmental risk factors for developing schizophrenic
      psychoses. This is mainly due to the following observations. (i) Cannabis at high
      doses can cause acute transient psychotic symptoms even in healthy individuals.
      (ii) Patients with schizophrenia abuse cannabis more often than age-matched
      healthy controls. OBJECTIVES: It is still controversial whether cannabis use can
      cause schizophrenic psychoses that would not have occurred otherwise. In our
      review, we have critically evaluated the evidence for a causal link between
      cannabis use and schizophrenic psychoses. METHODS: A systematic literature review
      in PubMed, ISI Web of Science and PsycINFO was carried out using the following
      keywords: cannabis, marijuana, THC, hashish, psychosis, schizophrenia.
      CONCLUSIONS: We have concluded that although a causal relationship between
      cannabis use and schizophrenic psychoses cannot be definitely proven, the
      available evidence strongly supports its plausibility. Furthermore, the results
      of the review indicate that cannabis might cause psychosis especially in
      individuals with a predisposition for schizophrenia and in adolescents with an
      early onset of cannabis use.

PMID- 23139067
TI  - [Secondary prevention of ischemic stroke--Part 1].

PMID- 23139066
TI  - [The writer Rudolf Ditzen [Hans Fallada] (1893-1947) as a morphine addict in the
      Stralsund Provincial Sanatorium in 1921].
AB  - The work presented here analyses the in-patient psychiatric treatment, which
      remained unconsidered in the relevant biographies, of Rudolf Ditzen in the
      Stralsund Provincial Sanatorium from 5 January to 14 February 1921 with the
      diagnoses of "morphine addiction" and "degenerative psychopathic constitution".
      For this purpose the medical report on Ditzen, which has come to light again, was
      evaluated, and the treatment classified in its medical-historical context and the
      making of the diagnosis discussed against the background of Ditzen's psychosocial
      development. In the case of a combination of diagnoses typical for the time,
      against the background of Ditzen's difficult psychosocial development, which was
      likewise typical for its time, the result was a not entirely typical treatment
      for addiction under the custodial conditions of institutional psychiatry around
      1920. Ditzen's hospitalisation with a comparatively mild type of symptoms is to
      be viewed against the background of a lack of extramural treatment structures. It
      is not certain whether Ditzen deliberately used the hospital as a space for
      withdrawal and protection.

PMID- 23139068
TI  - Osteocalcin: skeletal and extra-skeletal effects.
AB  - Osteocalcin (OC) is a non-collagenous, vitamin K-dependent protein secreted in
      the late stage of osteoblasts differentiation. The presence of the three residues
      of gamma-carbossiglutamatic acid, specific of the active form of OC protein,
      allows the protein to bind calcium and consequently hydroxyapatite. The
      osteoblastic OC protein is encoded by the bone gamma-carbossiglutamate gene whose
      transcription is principally regulated by the Runx2/Cbfa1 regulatory element and
      stimulated by vitamin D(3) through a steroid-responsive enhancer sequence. Even
      if data obtained in literature are controversial, the dual role of OC in bone can
      be presumed as follows: firstly, OC acts as a regulator of bone mineralization;
      secondly, OC regulates osteoblast and osteoclast activity. Recently the metabolic
      activity of OC, restricted to the un-carboxylated form has been demonstrated in
      osteoblast-specific knockout mice. This effect is mediated by the regulation of
      pancreatic beta-cell proliferation and insulin secretion and adiponectin
      production by adipose tissue and leads to the regulation of glucose metabolism
      and fat mass. Nevertheless, clinical human studies only demonstrated the
      correlation between OC levels and factors related to energy metabolism. Thus
      further investigations in humans are required to demonstrate the role of OC in
      the regulation of human energy metabolism. Moreover, it is presumable that OC
      also acts on blood vessels by inducing angiogenesis and pathological
      mineralization. This review highlights the recent studies concerning skeletal and
      extra-skeletal effects of OC.

PMID- 23139069
TI  - Light-emitting diode photobiomodulation: effect on bone formation in
      orthopedically expanded suture in rats--early bone changes.
AB  - The aim of this experimental study was to evaluate histomorphometrically the
      effects of light-emitting diode (LED) photobiomodulation therapy (LPT) on bone
      formation in response to expansion of the interpremaxillary suture in rats.
      Twenty male, 50- to 60-day-old Wistar rats were divided into two equal groups
      (control and experimental). Both groups were subjected to expansion for 5 days,
      and 50 cN of force was applied to the maxillary incisors with helical spring. An
      OsseoPulse(r) LED device, 618-nm wavelength and 20-mW/cm(2) output power
      irradiation, was applied to the interpremaxillary suture for 10 days. Bone
      formation in the sutural area was histomorphometrically evaluated, including the
      amount of new bone formation (in square micrometers), number of osteoblasts,
      number of osteoclasts, and number of vessels. Mann-Whitney U test was used for
      statistical evaluation at p < 0.025 level. Significant differences were found
      between groups for all investigated histomorphometric parameters. New bone
      formation area (p = 0.024, 1.48-fold), number of osteoblasts (p < 0.001, 1.59
      fold), number of osteoclasts (p = 0.004, 1.43-fold), and number of vessels (p =
      0.007, 1.67-fold) showed higher values in the experimental group than the
      control. Bone histomorphometric measurements revealed that bone architecture in
      the LPT group was improved. The application of LPT can stimulate bone formation
      in the orthopedically expanded interpremaxillary suture during expansion and the
      early phase of the retention periods. 

PMID- 23139070
TI  - Influence of surface treatments and resin cement selection on bonding to
      zirconia.
AB  - This study aimed to evaluate the surface changes caused in zirconia by different
      surface treatments and the influence of the surface treatment and cement
      selection on bonding to zirconia under aging. Sintered zirconia specimens were
      divided into five groups (n = 31) based on the surface treatment, namely,
      control, air abrasion, silica coating, laser and air abrasion + laser. After
      surface treatment, surface roughness and microscope analyses were performed on
      one specimen of each group. Composite cylinders were then bonded to conditioned
      ceramics using RelyX U100 (RXU), Clearfil Esthetic Cement (CEC) and Panavia F
      (PF) (n = 10). After 24 h, the bonded specimens were subjected to thermal cycling
      (6,000 times), and then, a shear bond strength test was conducted. The roughness
      values were analysed using Kruskal-Wallis and Mann-Whitney U tests, and the bond
      strengths were analysed by two-way analysis of variance and Duncan's test. The
      relationship between the roughness and the bond strength was determined by
      Spearman's correlation analysis. Specimens subjected to surface treatments were
      rougher than the control specimen (p < 0.000). However, there were no significant
      differences between the air abrasion and air abrasion + laser groups and the
      silica coating and laser groups. Specimens treated with laser showed lower bond
      strengths irrespective of the resin cement used. CEC and/or PF showed higher bond
      strengths than RXU for each surface treatment group. No significant relationship
      was observed between the roughness and the bond strength. The results of this
      study showed that all the surface treatments, except for laser irradiation, were
      suitable for treating zirconia ceramics. Cement selection was found to be more
      important than surface treatment, and phosphate monomer-containing cements were
      suitable for cementing zirconia.

PMID- 23139071
TI  - Light-activated disinfection using a light-emitting diode lamp in the red
      spectrum: clinical and microbiological short-term findings on periodontitis
      patients in maintenance. A randomized controlled split-mouth clinical trial.
AB  - Eradication or suppression of pathogens is a major goal in periodontal therapy.
      Due to the increase in antibiotic resistance, the need of new disinfection
      therapies is raising. Photodynamic therapy (PDT) has demonstrated anti-infective
      potential. No data are available on the use of light-emitting diode (LED) lights
      as the light source in PDT. The aim of this study was to investigate the
      microbiological and clinical adjunctive outcome of a new photodynamic LED device,
      compared to scaling and root planing in periodontitis patients in maintenance
      [supportive periodontal therapy (SPT)]. In this masked, split-mouth design study,
      30 treated chronic periodontitis subjects (mean age, 46.2 years; 13 males) in SPT
      were included. Two residual interdental sites with probing pocket depth (PPD) >=
      5 mm in two opposite quadrants, with positive bleeding on probing (BOP) and
      comparable periodontal breakdown, were selected. PPD, BOP and subgingival
      microbiological samples for real-time PCR analysis (Carpegen(r) PerioDiagnostics,
      Carpegen GmbH, Munster, Germany) were recorded at baseline and 1 week after
      treatment. Scaling and root planing was performed under local anesthesia.
      Randomly one of the sites was selected to receive adjunctive photodynamic therapy
      by inserting a photosensitizer (toluidine blue O solution) and exposing it to a
      LED light in the red spectrum (Fotosan, CMS Dental, Copenhagen, Denmark),
      according to the manufacturer's instructions. After 1 week, 73 % of the control
      sites and 27 % of the test sites were still BOP+. These differences compared to
      baseline values and in-between groups were statistically significantly different
      (p < 0.001). Mean PPD decreased from 5.47 mm (+/-0.68) to 4.73 mm (+/-0.74, p <
      0.001) in control sites and from 5.63 mm (+/-0.85) to 4.43 mm (+/-1.25, p <
      0.001, test vs control p = 0.01) in the test group. Microbiologically, higher
      reductions of relative proportions of red complex bacteria were observed in test
      sites (68.1 vs. 4.1 %; p = 0.01). This study showed that adjunctive photodynamic
      treatment by LED light may enhance short-term clinical and microbiological
      outcome in periodontitis subjects in SPT.

PMID- 23139072
TI  - Physical properties and cellular responses to calcium phosphate coating produced
      by laser rapid forming on titanium.
AB  - In order to improve the surface bioactivity of titanium implants, CaCO3 and
      CaHPO4.2H2O powder was used to fabricate a calcium phosphate (CaP) coating using
      laser rapid forming (LRF) technology. The surface characterization showed that a
      porous and beta-tricalcium phosphate (beta-TCP) layer with small amount of alpha
      TCP was formed on commercial pure titanium (Ti). The bonding strength between the
      coating and the Ti substrate was above 40.17 MPa measured by the means of pull
      off test. The elastic modulus and the average microhardness of the coating were
      117.61 GPa and 431.2 HV0.1, respectively. Through the static immersion test, it
      was proved that the coating could not only prevent the corrosion of Ti but also
      promote the redeposition of beta-TCP in artificial saliva. Osteoblasts possessed
      good attachment performance and strong proliferation ability on the surface of
      LRF coating (p < 0.05) in our cell experiments. This result demonstrated that the
      LRF coating could improve the surface cytocompatibility of titanium. Using
      scanning electron microscopy observation, it was found that osteoblasts grown on
      LRF coating formed multiple layers in pours. The result of reverse transcription
      PCR analysis demonstrated that the expressions of ITGbeta1 and BMP-2 were
      significantly (p < 0.05) upregulated on the LRF coating in a time-dependent
      manner, compared with uncoated Ti. These findings suggested that the LRF
      technology might be a promising potential treatment for fabricating CaP coatings
      on titanium implants.

PMID- 23139073
TI  - Low-level laser therapy improves crescentic glomerulonephritis in rats.
AB  - Low-level laser therapy (LLLT) can reduce inflammation in a variety of clinical
      conditions, including trauma, postherpetic neuralgia, and rheumatoid arthritis.
      However, the effect of LLLT on internal organs has not been elucidated. The goal
      of the present study was to investigate the anti-inflammatory effect of daily
      external LLLT in an animal model of crescentic glomerulonephritis. Crescentic
      glomerulonephritis was induced in male Wister Kyoto rats by intravenous injection
      of antibody for glomerular basement membrane (GBM). The rats were irradiated with
      a low-reactive level diode laser with an infrared wavelength of 830 nm from the
      shaved skin surface once a day for 14 days (irradiation spot size on the skin
      surface, 2.27 cm(2); power intensity, 880 mW/cm(2); irradiation mode, continuous
      mode; irradiation time, 250 s; energy, 500 J; energy density, 220 J/cm(2)). After
      laser irradiation for 14 days, animals were killed, and the extent of
      inflammation was evaluated. Expression of gene for inflammatory cytokines
      including interleukin (IL)-1beta and tumor necrosis factor alpha (TNF-alpha) was
      assessed by reverse transcription polymerase chain reaction. Crescent formation
      in glomeruli and infiltration of macrophages and lymphocytes were assessed by
      histochemical observation. Injection of anti-GBM antibody induced severe
      glomerulonephritis with crescent formation. Histological observations indicated
      that LLLT suppressed crescent formation and infiltration of ED1+ macrophages and
      CD8+ lymphocytes into the glomeruli. LLLT attenuated the levels of IL-1beta and
      TNF-alpha messenger RNA in the renal cortex. Externally directed LLLT suppresses
      the activity of rat anti-GBM crescentic glomerulonephritis in rats. LLLT has the
      potential to be used for direct treatment of glomerulonephritis. 

PMID- 23139074
TI  - C3'/C4'-Stereochemical Effects of Digitoxigenin alpha-L-/alpha-D-Glycoside in
      Cancer Cytotoxicity.
AB  - Sweet'n low in stereo: A Wharton reaction was employed along with a
      diastereoselective palladium-catalyzed glycosylation and other post-glycosylation
      transformations to synthesize digitoxin analogues. Cytotoxic evaluation against a
      panel of cancer cell lines uncovered the stereochemical and substitutional limits
      of the C3'/C4'-hydroxy functionality in digitoxin monosaccharide.

PMID- 23139075
TI  - IgE-mediated immune responses and airway detection of Aspergillus and Candida in
      adult cystic fibrosis.
AB  - BACKGROUND: The recovery of Aspergillus and Candida from the respiratory
      secretions of patients with cystic fibrosis (CF) is common. Their relationship to
      the development of allergic sensitization and effect on lung function has not
      been established. Improved techniques to detect these organisms are needed to
      increase knowledge of these effects. METHODS: A 2-year prospective observational
      cohort study was performed. Fifty-five adult patients with CF had sputum
      monitored for Aspergillus by culture and real-time polymerase chain reaction and
      Candida by CHROMagar and carbon assimilation profile (API/ID 32C). Skin prick
      tests and ImmunoCAP IgEs to a panel of common and fungal allergens were
      performed. Lung function and pulmonary exacerbation rates were monitored over 2
      years. RESULTS: Sixty-nine percent of patient sputum samples showed chronic
      colonization with Candida and 60% showed colonization with Aspergillus. There was
      no association between the recovery of either organism and the presence of
      specific IgE responses. There was no difference in lung function decline for
      patients with Aspergillus or Candida colonization compared with those without
      (FEV1 percent predicted, P = .41 and P = .90, respectively; FVC % predicted, P =
      .87 and P = .37, respectively). However, there was a significantly greater
      decline in FEV1 and increase in IV antibiotic days for those sensitized to
      Aspergillus (FEV1 decline, P = .03; IV antibiotics days, P = .03). CONCLUSIONS:
      Allergic sensitization is not associated with recovery of Candida or Aspergillus
      from the sputum of patients with CF. Aspergillus but not Candida sensitization is
      associated with greater lung function decline and pulmonary exacerbations.

PMID- 23139076
TI  - Fast drum strokes: novel and convergent features of sonic muscle ultrastructure,
      innervation, and motor neuron organization in the Pyramid Butterflyfish
      (Hemitaurichthys polylepis).
AB  - Sound production that is mediated by intrinsic or extrinsic swim bladder
      musculature has evolved multiple times in teleost fishes. Sonic muscles must
      contract rapidly and synchronously to compress the gas-filled bladder with
      sufficient velocity to produce sound. Muscle modifications that may promote rapid
      contraction include small fiber diameter, elaborate sarcoplasmic reticulum (SR),
      triads at the A-I boundary, and cores of sarcoplasm. The diversity of innervation
      patterns indicate that sonic muscles have independently evolved from different
      trunk muscle precursors. The analysis of sonic motor pathways in distantly
      related fishes is required to determine the relationships between sonic muscle
      evolution and function in acoustic signaling. We examined the ultrastructure of
      sonic and adjacent hypaxial muscle fibers and the distribution of sonic motor
      neurons in the coral reef Pyramid Butterflyfish (Chaetodontidae: Hemitaurichthys
      polylepis) that produces sound by contraction of extrinsic sonic muscles near the
      anterior swim bladder. Relative to adjacent hypaxial fibers, sonic muscle fibers
      were sparsely arranged among the endomysium, smaller in cross-section, had longer
      sarcomeres, a more elaborate SR, wider t-tubules, and more radially arranged
      myofibrils. Both sonic and non-sonic muscle fibers possessed triads at the Z
      line, lacked sarcoplasmic cores, and had mitochondria among the myofibrils and
      concentrated within the peripheral sarcoplasm. Sonic muscles of this derived
      eutelost possess features convergent with other distant vocal taxa (other
      euteleosts and non-euteleosts): small fiber diameter, a well-developed SR, and
      radial myofibrils. In contrast with some sonic fishes, however, Pyramid
      Butterflyfish sonic muscles lack sarcoplasmic cores and A-I triads. Retrograde
      nerve label experiments show that sonic muscle is innervated by central and
      ventrolateral motor neurons associated with spinal nerves 1-3. This restricted
      distribution of sonic motor neurons in the spinal cord differs from many
      euteleosts and likely reflects the embryological origin of sonic muscles from
      hypaxial trunk precursors rather than occipital somites.

PMID- 23139077
TI  - Detection of drug-induced conformational change of a transmembrane protein in
      lipid bilayers using site-directed spin labeling.
AB  - As a target of antiviral drugs, the influenza A M2 protein has been the focus of
      numerous structural studies and has been extensively explored as a model ion
      channel. In this study, we capitalize on the expanding body of high-resolution
      structural data available for the M2 protein to design and interpret site
      directed spin-labeling electron paramagnetic resonance spectroscopy experiments
      on drug-induced conformational changes of the M2 protein embedded in lipid
      bilayers. We obtained data in the presence of adamantane drugs for two different
      M2 constructs (M2TM 22-46 and M2TMC 23-60). M2TM peptides were spin labeled at
      the N-terminal end of the transmembrane domain. M2TMC peptides were spin labeled
      site specifically at cysteine residues substituted for amino acids within the
      transmembrane domain (L36, I39, I42, and L43) and the C-terminal amphipathic
      helix (L46, F47, F48, C50, I51, Y52, R53, F54, F55, and E56). Addition of
      adamantane drugs brought about significant changes in measured electron
      paramagnetic resonance spectroscopy environmental parameters consistent with
      narrowing of the transmembrane channel pore and closer packing of the C-terminal
      amphipathic helices.

PMID- 23139078
TI  - Predictors of functional outcome after emergency carotid artery stenting and
      intra-arterial thrombolysis for treatment of acute stroke associated with
      obstruction of the proximal internal carotid artery and tandem downstream
      occlusion.
AB  - BACKGROUND AND PURPOSE: Patients who develop severe stroke symptoms due to acute
      internal carotid artery occlusion eventually in combination with a thromboembolic
      obstruction of the middle cerebral artery incur a major risk of developing
      extensive MCA infarction with a poor outcome. The purpose of this study was to
      evaluate the outcome for patients with tandem occlusions in the MCA and/or distal
      ICA, retrospectively, who had undergone stent implantation in the proximal
      segment of the ICA in addition to intra-arterial thrombolysis. MATERIALS AND
      METHODS: Thirty-five patients with tandem occlusions of the MCA and/or distal ICA
      and acute occlusion of the proximal ICA underwent stent implantation for the
      proximal ICA occlusion and IAT for the tandem occlusion. Clinical outcome
      measures were assessed on admission and at discharge by using the National
      Institutes of Health Stroke Scale as well as 3 months after treatment by using
      the modified Rankin Scale. RESULTS: The median NIHSS score on admission was 12
      (range, 6-22). All patients had patent flow into the M1 and ICA after carotid
      artery stent placement and IAT. After the procedure, 19 patients (54.3%) were
      TICI grade III; 7 (20.0%), TICI grade IIb; and 9 (25.7%), TICI grade IIa.
      Symptomatic intracerebral hemorrhage occurred in 1 patient (2.9%). The overall
      mortality rate was 11.4% (4/35). At 3-month follow-up, the median NIHSS score was
      4 (range, 1-17). NIHSS score at admission and TICI grade were all found to be
      independently associated with an unfavorable outcome at 3 months. CONCLUSIONS:
      Initial stroke severity, degree of successful revascularization, and the side of
      ischemia were found to independently predict the functional outcome at 3 months
      after treatment.

PMID- 23139079
TI  - Improved conspicuity and delineation of high-grade primary and metastatic brain
      tumors using "restriction spectrum imaging": quantitative comparison with high B
      value DWI and ADC.
AB  - BACKGROUND AND PURPOSE: Restriction spectrum imaging is a sensitive DWI technique
      for probing separable water diffusion compartments in tissues. Here, we evaluate
      RSI-CMs derived from the spherically-restricted water compartment for improved
      tumor conspicuity and delineation from nontumor tissue and reduced sensitivity to
      edema compared with high-b-value DWI and ADC. MATERIALS AND METHODS: RSI was
      performed in 10 presurgical patients: 4 with glioblastoma, 3 with primary CNS
      lymphoma, and 3 with metastatic brain tumors. Multidirectional DWI data were
      collected at b = 500, 1500, and 4000 s/mm(2). Quantification of tumor
      conspicuity, edema conspicuity, and relative sensitivity to edema for RSI-CMs;
      DWI at b = 4000 (DWI-4000); and ADC were compared in manually drawn VOIs.
      Receiver operating characteristic curves were used to evaluate the sensitivity
      and specificity of each method for delineating tumor from normal-appearing WM.
      RESULTS: Significant TC was seen with both RSI-CMs and DWI-4000, but not ADC.
      Significant EC was seen with ADC, but not RSI-CMs or DWI-4000. Significantly
      greater TC was seen with RSI-CMs compared with DWI-4000. Significantly reduced
      RSE was seen with RSI-CMs compared with both DWI-4000 and ADC. Greater
      sensitivity and specificity for delineating tumor from normal-appearing WM were
      seen with RSI-CMs (AUC = 0.91) compared with both DWI-4000 (AUC = 0.77) and ADC
      (AUC = 0.66). CONCLUSIONS: RSI-CMs offer improved conspicuity and delineation of
      high-grade primary and metastatic brain tumors and reduced sensitivity to edema
      compared with high-b-value DWI and ADC.

PMID- 23139080
TI  - MR imaging of hippocampal asymmetry at 3T in a multiethnic, population-based
      sample: results from the Dallas Heart Study.
AB  - BACKGROUND AND PURPOSE: Asymmetry of the hippocampus is regarded as an important
      clinical finding, but limited data on hippocampal asymmetry are available for the
      general population. Here we present hippocampal asymmetry data from the Dallas
      Heart Study determined by automated methods and its relationship to age, sex, and
      ethnicity. MATERIALS AND METHODS: 3D magnetization-prepared rapid acquisition of
      gradient echo MR imaging was performed in 2082 DHS-2 participants. The MR images
      were analyzed by using 2 standard automated brain-segmentation programs, FSL
      FIRST and FreeSurfer. Individuals with imaging errors, self-reported stroke, or
      major structural abnormalities were excluded. Statistical analyses were performed
      to determine the significance of the findings across age, sex, and ethnicity.
      RESULTS: At the 90th percentile, FSL-FIRST demonstrated hippocampal asymmetry of
      9.8% (95% CI, 9.3%-10.5%). The 90th percentile of hippocampal asymmetry, measured
      by the difference in right and left hippocampi volume and the larger hippocampus,
      was 17.9% (95% CI, 17.0%-19.1%). Hippocampal asymmetry increases with age
      (P=.0216), men have greater asymmetry than women as shown by FSL-FIRST (P=.0036),
      but ethnicity is not significantly correlated with asymmetry. To confirm these
      findings, we used FreeSurfer. FreeSurfer showed asymmetry of 4.4% (95% CI, 4.3%
      4.7%) normalized to total volume and 8.5% (95% CI, 8.3%-9.0%) normalized by
      difference/larger hippocampus. FreeSurfer also showed that hippocampal asymmetry
      increases with age (P=.0024) and that men had greater asymmetry than women
      (P=.03). CONCLUSIONS: There is a significant degree of hippocampal asymmetry in
      the population. The data provided will aid in the research, diagnosis, and
      treatment of temporal lobe epilepsy and other neurologic disease.

PMID- 23139082
TI  - Whence genes in pieces: reconstruction of the exon-intron gene structures of the
      last eukaryotic common ancestor and other ancestral eukaryotes.
AB  - In eukaryotes, protein-coding sequences are interrupted by non-coding sequences
      known as introns. During mRNA maturation, introns are excised by the spliceosome
      and the coding regions, exons, are spliced to form the mature coding region. The
      intron densities widely differ between eukaryotic lineages, from 6 to 7 introns
      per kb of coding sequence in vertebrates, some invertebrates and green plants, to
      only a few introns across the entire genome in many unicellular eukaryotes.
      Evolutionary reconstructions using maximum likelihood methods suggest intron-rich
      ancestors for each major group of eukaryotes. For the last common ancestor of
      animals, the highest intron density of all extant and extinct eukaryotes was
      inferred, at 120-130% of the human intron density. Furthermore, an intron density
      within 53-74% of the human values was inferred for the last eukaryotic common
      ancestor. Accordingly, evolution of eukaryotic genes in all lines of descent
      involved primarily intron loss, with substantial gain only at the bases of
      several branches including plants and animals. These conclusions have substantial
      biological implications indicating that the common ancestor of all modern
      eukaryotes was a complex organism with a gene architecture resembling those in
      multicellular organisms. Alternative splicing most likely initially appeared as
      an inevitable result of splicing errors and only later was employed to generate
      structural and functional diversification of proteins.

PMID- 23139081
TI  - Dimensions of religiosity and access to religious social capital: correlates with
      substance use among urban adolescents.
AB  - Although some evidence indicates that religiosity may be protective against
      substance use in the urban youth population, limited research has investigated
      the effects of multiple dimensions of religiosity on substance use in this
      population. In this study, a sample of 301 urban adolescents was used (a) to test
      the effects of three dimensions of religiosity (social religiosity, perceived
      religious support, and private religiosity) as well as proximity to religious
      institutions and (b) to determine their correlates with tobacco, alcohol, and
      marijuana use. It was hypothesized that all three dimensions of religiosity would
      act as protective factors against all types of substance use and that proximity
      to religious institutions from adolescents' routine locations would also serve as
      a protective factor against any type of substance use. Results of logistic
      regression analysis showed that social religiosity and perceived religious
      support were protective against marijuana and tobacco use, respectively. Private
      religiosity was not protective against any type of substance use. Proximity to
      religious institutions was protective against alcohol use. These findings suggest
      the importance of examining multiple dimensions of religiosity when investigating
      substance use in urban youth and offer initial evidence of the importance of
      proximity to religious institutions as a protective factor against substance use.

PMID- 23139083
TI  - Antibacterial strategies from the sea: polymer-bound cl-catechols for prevention
      of biofilm formation.
AB  - Inspired by the amino acid 2-chloro-4,5-dihydroxyphenylalanine (Cl-DOPA), present
      in the composition of the proteinaceous glue of the sandcastle worm Phragmatopoma
      californica, a simple strategy is presented to confer antifouling properties to
      polymer surfaces using (but not releasing) a bioinspired biocide. Cl-Dopamine is
      used to functionalize polymer materials and hydrogel films easily, to prevent
      biofilm formation on them.

PMID- 23139084
TI  - Compared performance of high-sensitivity cameras dedicated to myocardial
      perfusion SPECT: a comprehensive analysis of phantom and human images.
AB  - Differences in the performance of cadmium-zinc-telluride (CZT) cameras or
      collimation systems that have recently been commercialized for myocardial SPECT
      remain unclear. In the present study, the performance of 3 of these systems was
      compared by a comprehensive analysis of phantom and human SPECT images. METHODS:
      We evaluated the Discovery NM 530c and DSPECT CZT cameras, as well as the Symbia
      Anger camera equipped with an astigmatic (IQ x SPECT) or parallel-hole
      (conventional SPECT) collimator. Physical performance was compared on
      reconstructed SPECT images from a phantom and from comparable groups of healthy
      subjects. RESULTS: Classifications were as follows, in order of performance. For
      count sensitivity on cardiac phantom images (counts x s(-1) x MBq(-1)), DSPECT
      had a sensitivity of 850; Discovery NM 530c, 460; IQ x SPECT, 390; and
      conventional SPECT, 130. This classification was similar to that of myocardial
      counts normalized to injected activities from human images (respective mean
      values, in counts x s(-1) x MBq(-1): 11.4 +/- 2.6, 5.6 +/- 1.4, 2.7 +/- 0.7, and
      0.6 +/- 0.1). For central spatial resolution: Discovery NM 530c was 6.7 mm;
      DSPECT, 8.6 mm; IQ x SPECT, 15.0 mm; and conventional SPECT, 15.3 mm, also in
      accordance with the analysis of the sharpness of myocardial contours on human
      images (in cm(-1): 1.02 +/- 0.17, 0.92 +/- 0.11, 0.64 +/- 0.12, and 0.65 +/-
      0.06, respectively). For contrast-to-noise ratio on the phantom: Discovery NM
      530c had a ratio of 4.6; DSPECT, 4.1; IQ x SPECT, 3.9; and conventional SPECT,
      3.5, similar to ratios documented on human images (5.2 +/- 1.0, 4.5 +/- 0.5, 3.9
      +/- 0.6, and 3.4 +/- 0.3, respectively). CONCLUSION: The performance of CZT
      cameras is dramatically higher than that of Anger cameras, even for human SPECT
      images. However, CZT cameras differ in that spatial resolution and contrast-to
      noise ratio are better with the Discovery NM 530c, whereas count sensitivity is
      markedly higher with the DSPECT.

PMID- 23139085
TI  - Incidental diffuse thyroid 18F-FDG uptake related to autoimmune thyroiditis may
      be a favorable prognostic factor in advanced breast cancer.
AB  - Patients with breast cancer have a relatively high prevalence of diffuse thyroid
      uptake of (18)F-FDG related to thyroid autoimmunity. It is postulated that the
      presence of thyroid autoimmunity has prognostic implications for breast cancer.
      The aim of this study was to evaluate the prognostic value of incidental diffuse
      thyroid uptake in breast cancer patients. METHODS: This was a retrospective
      observational cohort study in a tertiary referral hospital. We evaluated a total
      of 564 patients who had undergone surgery for primary breast cancer between
      January 2006 and December 2009. Patients were divided into 2 groups according to
      their diffuse thyroid uptake. The main outcome measure was disease-free survival.
      RESULTS: Of the 564 patients, 108 (19.1%) showed diffuse thyroid uptake. The
      median follow-up period was 36.0 mo (range, 1.0-77.0 mo). Both thyroperoxidase
      and thyroglobulin antibody titers were higher in patients with thyroid uptake
      than in those without (P < 0.001 for both). Of the 108 patients with thyroid
      uptake, 5 had a recurrence of breast cancer during the follow-up, whereas 85
      without uptake had a recurrence (log-rank statics, 12.28; P < 0.001). The
      association between diffuse thyroid uptake and tumor recurrence was not
      significant in multivariate analysis of patients with early-stage breast cancer
      (hazard ratio, 0.26; 95% confidence interval, 0.06-1.10; P = 0.067). However, the
      association between diffuse thyroid uptake and breast cancer recurrence was
      statistically significant in multivariate analysis with adjustment for several
      prognostic variables (hazard ratio, 0.19; 95% confidence interval, 0.57-0.62; P =
      0.006). CONCLUSION: Incidental diffuse thyroid uptake related to autoimmune
      thyroiditis was an independently favorable prognostic factor in advanced breast
      cancer. These findings support evidence that thyroid autoimmunity has a
      beneficial effect on the outcomes of breast cancer patients.

PMID- 23139086
TI  - A unique matched quadruplet of terbium radioisotopes for PET and SPECT and for
      alpha- and beta- radionuclide therapy: an in vivo proof-of-concept study with a
      new receptor-targeted folate derivative.
AB  - Terbium offers 4 clinically interesting radioisotopes with complementary physical
      decay characteristics: (149)Tb, (152)Tb, (155)Tb, and (161)Tb. The identical
      chemical characteristics of these radioisotopes allow the preparation of
      radiopharmaceuticals with identical pharmacokinetics useful for PET ((152)Tb) and
      SPECT diagnosis ((155)Tb) and for alpha- ((149)Tb) and beta(-)-particle ((161)Tb)
      therapy. The goal of this proof-of-concept study was to produce all 4 terbium
      radioisotopes and assess their diagnostic and therapeutic features in vivo when
      labeled with a folate-based targeting agent. METHODS: (161)Tb was produced by
      irradiation of (160)Gd targets with neutrons at Paul Scherrer Institute or
      Institut Laue-Langevin. After neutron capture, the short-lived (161)Gd decays to
      (161)Tb. (149)Tb, (152)Tb, and (155)Tb were produced by proton-induced spallation
      of tantalum targets, followed by an online isotope separation process at
      ISOLDE/CERN. The isotopes were purified by means of cation exchange
      chromatography. For the in vivo studies, we used the DOTA-folate conjugate cm09,
      which binds to folate receptor (FR)-positive KB tumor cells. Therapy experiments
      with (149)Tb-cm09 and (161)Tb-cm09 were performed in KB tumor-bearing nude mice.
      Diagnostic PET/CT ((152)Tb-cm09) and SPECT/CT ((155)Tb-cm09 and (161)Tb-cm09)
      studies were performed in the same tumor mouse model. RESULTS: Carrier-free
      terbium radioisotopes were obtained after purification, with activities ranging
      from approximately 6 MBq (for (149)Tb) to approximately 15 MBq (for (161)Tb). The
      radiolabeling of cm09 was achieved in a greater than 96% radiochemical yield for
      all terbium radioisotopes. Biodistribution studies showed high and specific
      uptake in FR-positive tumor xenografts (23.8% +/- 2.5% at 4 h after injection,
      22.0% +/- 4.4% at 24 h after injection, and 18.4% +/- 1.8% at 48 h after
      injection). Excellent tumor-to-background ratios at 24 h after injection (tumor
      to blood, ~ 15; tumor to liver, ~ 5.9; and tumor to kidney, ~ 0.8) allowed the
      visualization of tumors in mice using PET ((152)Tb-cm09) and SPECT ((155)Tb-cm09
      and (161)Tb-cm09). Compared with no therapy, alpha- ((149)Tb-cm09) and beta(-)
      particle therapy ((161)Tb-cm09) resulted in a marked delay in tumor growth or
      even complete remission (33% for (149)Tb-cm09 and 80% for (161)Tb-cm09) and a
      significantly increased survival. CONCLUSION: For the first time, to our
      knowledge, 4 terbium radionuclides have been tested in parallel with tumor
      bearing mice using an FR targeting agent. Along with excellent tumor
      visualization enabled by (152)Tb PET and (155)Tb SPECT, we demonstrated the
      therapeutic efficacy of the alpha-emitter (149)Tb and beta(-)-emitter (161)Tb.

PMID- 23139087
TI  - PET of glucagonlike peptide receptor upregulation after myocardial ischemia or
      reperfusion injury.
AB  - Glucagonlike peptide (GLP-1) and its receptor (GLP-1R) exhibit cardioprotective
      effects after myocardial ischemia and reperfusion (MI/R) in both animal studies
      and clinical trials. However, the kinetics of GLP-1R expression in the
      infarcted/ischemic myocardium has not yet been explored. The purpose of this
      study was to monitor the presence and time course of regional myocardial GLP-1R
      expression after MI/R with noninvasive PET. METHODS: Male Sprague-Dawley rats
      underwent a 45-min transient left coronary artery occlusion, followed by
      reperfusion. The myocardial infarction was confirmed by electrocardiogram and
      cardiac ultrasound. In vivo PET was performed to determine myocardial uptake of
      (18)F-FBEM-Cys(40)-exendin-4 at different time points after reperfusion. The
      localization of (18)F-FBEM-Cys(40)-exendin-4 accumulation was determined by
      coregistering (18)F-FDG PET and CT images. Ex vivo autoradiography, GLP-1R
      immunohistochemical staining, and Western blot analysis were performed to confirm
      the PET results. RESULTS: Myocardial origin and infarcted/ischemic area
      localization of (18)F-FBEM-Cys(40)-exendin-4 accumulation was confirmed by
      coregistration of small-animal CT and (18)F-FDG images. At 8 h after MI/R, tracer
      uptake in the infarcted/ischemic region was 0.37 +/- 0.05 percentage injected
      dose per gram, significantly higher than that in the control group (P < 0.01).
      The localized tracer uptake decreased, relative to the 8-h time point, but was
      still significantly higher than the control group on days 1 and 3 after MI/R. At
      2 wk after MI/R, the tracer uptake in the affected area showed no significant
      difference, compared with that in the healthy myocardium. Autoradiography showed
      the same trend of (18)F-FBEM-Cys(40)-exendin-4 uptake in the myocardial
      infarcted/ischemic area. The specificity of tracer uptake into ischemic
      myocardium was supported by decreased tracer uptake after the rats were
      pretreated with an excess amount of unlabeled exendin-4. Immunohistochemical
      staining and Western blotting of GLP-1R protein of excised cardiac sections
      confirmed that the change in uptake observed by PET corresponded to a change in
      GLP-1R expression. CONCLUSION: Noninvasive PET using (18)F-FBEM-Cys(40)-exendin-4
      revealed a dynamic pattern of GLP-1R upregulation in the infarcted/ischemic area
      after MI/R. The imaging results will deepen our understanding of the mechanism of
      the cardioprotective effect of GLP-1 and its analogs and potentially provide
      guidance for optimization of the time frame of therapeutic intervention.

PMID- 23139088
TI  - A vaccinia virus encoding the human sodium iodide symporter facilitates long-term
      image monitoring of virotherapy and targeted radiotherapy of pancreatic cancer.
AB  - To assess therapeutic response and potential toxicity of oncolytic virotherapy, a
      noninvasive, deep-tissue imaging modality is needed. This study aimed to assess
      the feasibility, parameters, and determining factors of serial imaging and long
      term monitoring of virotherapy and the therapeutic response of pancreatic cancer
      xenografts treated with a vaccinia virus carrying the human sodium iodide
      symporter GLV-1h153. METHODS: Pancreatic cancer xenografts (PANC-1) in nude mice
      were treated systemically or intratumorally with GLV-1h153 and serially imaged
      using (124)I PET at 1, 2, 3, and 5 wk after viral injection. Signal intensity was
      compared with tumor therapeutic response and optical imaging, and tumors were
      histologically analyzed for morphology and the presence of virus. Autoradiography
      was performed using technetium-pertechnetate and gamma-scintigraphy to assess
      determining factors for radiouptake in tumors. Finally, the enhanced therapeutic
      effect of combination therapy with GLV-1h153 and systemic radioiodine was
      assessed. RESULTS: GLV-1h153 successfully facilitated serial long-term imaging of
      virotherapy, with PET signal intensity correlating to tumor response. GLV-1h153
      colonization of tumors mediated radioiodine uptake at potentially therapeutic
      doses. Successful radiouptake required the presence of virus, adequate blood
      flow, and viable tissue, whereas loss of signal intensity was linked to tumor
      death and necrosis. Finally, combining systemically administered GLV-1h153 and
      (131)I led to enhanced tumor kill when compared with virus or (131)I alone (P <
      0.01). CONCLUSION: GLV-1h153 is a promising oncolytic agent for the treatment,
      long-term imaging, and monitoring of therapeutic response in a xenograft model of
      pancreatic cancer. GLV-1h153 provided insight into tumor biologic activity and
      facilitated enhanced tumor kill when combined with systemic targeted
      radiotherapy. These results warrant further investigation into parameters and
      potential synergistic effects of combination therapy.

PMID- 23139089
TI  - Palivizumab immunoprophylaxis effectiveness in children with cystic fibrosis.
AB  - BACKGROUND: Evidence on the effectiveness of respiratory syncytial virus (RSV)
      immunoprophylaxis with palivizumab in children with cystic fibrosis (CF) is
      lacking. METHODS: We utilized Medicaid Extract files from 27 states from 1999 to
      2006 linked to the National Cystic Fibrosis Registry to establish a cohort of
      children 0-2 years with CF diagnosis. Eligible children entered the cohort after
      CF diagnosis and after RSV season onset, and were followed until season end,
      second birthday, death, or hospitalizations for reasons other then the study
      outcome. Two outcomes were examined: hospitalization for RSV infections (RSV-ha),
      or hospitalization for acute respiratory infections (ARI-ha). Palivizumab
      exposure was defined based on pharmacy or procedure claims as current (claim date
      plus 30 days), former (day 31-60 after a claim), and no exposure (days before the
      first or >60 days after any claim). Both outcomes were examined in a Cox
      regression model, adjusting for RSV risk factors and CF severity via exposure
      propensity score. RESULTS: The matched cohort included 1,974 infants (2,875
      infant seasons), who experienced 32 RSV-ha and 212 ARI-ha (3.9 and 26.2/1,000
      season months, respectively). Compared to periods of no use, the adjusted hazard
      ratio for current use was 0.57 (95% confidence interval [CI]: 0.20-1.60) for RSV
      related hospitalization and 0.85 (95% CI: 0.59-1.21) for ARI-related
      hospitalization. Each month of increasing age reduced the ARI-ha by 5.8%.
      CONCLUSION: RSV hospitalization incidence was low suggesting either little
      contribution of the virus to respiratory infections in patients with CF or lack
      of RSV testing. Unadjusted and adjusted RSV-hospitalization incidence rates
      suggested potentially positive effects of palivizumab, but results were
      inconclusive due to small event rates. Hospitalizations for acute respiratory
      illness with possible RSV contribution showed no association with palivizumab
      use, suggesting limited overall effect of palivizumab. Younger age greatly
      increased infection risk.

PMID- 23139090
TI  - Parthenium dermatitis.
AB  - Allergic contact dermatitis (ACD) to Parthenium hysterophorus is the most common
      cause of plant dermatitis in India. Parthenium dermatitis is caused by dry powder
      of leaves and flowers and hair-like structures (trichomes). Sesquiterpene
      lactones (SQLs) are the most important allergens responsible for ACD to
      parthenium. The different patterns include classical airborne contact dermatitis,
      chronic actinic dermatitis (CAD), exfoliative and widespread dermatitis. There is
      a definite trend towards a change from an airborne pattern to a CAD pattern in
      the natural history of parthenium dermatitis. In CAD, there is a reported
      increased sensitivity to UVB, UVA and even visible light. However, SQLs including
      parthenin, the major allergen in the Parthenium hysterophorus, has neither
      documented photoallergic nor phototoxic properties. Recently, the high
      photoreactivity of alpha-methylene-gamma-butyrolactone ring toward thymidine and
      resulting photoadducts has been proposed as an explanation of the progressive
      evolution of allergic contact dermatitis toward chronic actinic dermatitis.
      However, more data is required to reach a conclusion on the mechanism of
      photosensitivity in parthenium dermatitis. Sunlight, especially UV radiation, may
      have a role in increasing the germination capacity and the amount of allergens in
      the Compositae family, especially in parthenium plants under appropriate
      conditions like summer and spring, which may contribute to high prevalence of
      parthenium dermatitis especially in northern India.

PMID- 23139091
TI  - Determinants of patient satisfaction in an Australian emergency department fast
      track setting.
AB  - OBJECTIVES: To describe the relationship between waiting time and patient
      satisfaction, and to determine predictors of overall care rating in an emergency
      department (ED) fast-track setting. METHODS: A convenience sample of patients
      triaged to a fast-track unit were surveyed. Patient satisfaction was scored using
      a validated survey instrument, as well as a single overall care rating (poor to
      excellent). Median satisfaction scores were compared between each incremental
      hour of waiting time. Bivariate analysis was conducted between those who waited 1
      h or less, and those who waited longer. Ordered logistic regression was used to
      determine predictors of improved overall care rating. RESULTS: 236 patients
      completed surveys (response rate of 74%). Of these, 84% rated their care as
      either very good or excellent. There was a linear decrease in median satisfaction
      scores for each incremental hour of waiting time associated with half the odds of
      higher overall care rating after adjusting for presenting problem type, triage
      category, and treating clinician type (OR 0.53 95% CI 0.37 to 0.75 p<0.001).
      English language (OR 2.43 95% CI 1.33 to 4.42 p=0.004) and initial consultation
      by a nurse practitioner (NP) (OR 1.81 95% CI 1.03 to 3.31 p=0.038) were also
      found to be significant predictors of improved overall care rating. CONCLUSIONS:
      Waiting time was found to be highly predictive of patient satisfaction in an
      emergency fast-track unit with English language and NPs also associated with
      improved overall care rating. Future measures to improve patient satisfaction in
      fast-track units should focus on these factors.

PMID- 23139092
TI  - Audit of advanced airway management in UK Emergency Departments following the
      Fourth National Audit Project of the Royal College of Anaesthetists and Difficult
      Airway Society.

PMID- 23139093
TI  - Comparison of clinical outcomes between intermittent and continuous monitoring of
      central venous oxygen saturation (ScvO2) in patients with severe sepsis and
      septic shock: a pilot study.
AB  - BACKGROUND: The Surviving Sepsis Campaign (SSC) to improve patient outcomes in
      severe sepsis and septic shock contains recommendations for protocolised
      resuscitation including early goal-directed therapy (EGDT) resuscitation. In
      EGDT, central venous oxygen saturation (ScvO2) is measured as the target
      monitoring value. The objective of this study was to determine whether
      intermittent measurement of ScvO2 is as clinically effective as continuous
      monitoring in EGDT implementation. METHODS: This prospective, observational,
      pilot study was performed at an emergency room and general ward in ASAN Medical
      Centre, a 2680-bed teaching hospital. One hundred and six patients with severe
      sepsis or septic shock were enrolled and assigned to an intermittent monitoring
      group (n=53) or continuous monitoring group (n=53). RESULTS: Within 6 h of the
      EGDT, interventions by the treating physicians were assessed, including
      intravenous fluid administration, use of vasopressors and compliance with SSC
      bundles. After 6 h of the EGDT, 41.5% of all goals (primary outcome) were
      achieved in the intermittent group and 35.8% in the continuous group (p=0.550).
      Intensive Care Unit (ICU) mortality, hospital mortality and length of ICU stay
      did not differ between groups. CONCLUSIONS: During EGDT, intermittent ScvO2
      monitoring was not inferior to continuous ScvO2 monitoring when delivered within
      the first 6 h of intervention.

PMID- 23139094
TI  - CT coronary angiography: new risks for low-risk chest pain.
AB  - Widespread conservative management of low-risk chest pain has motivated the
      development of a rapid triage strategy based on CT coronary angiography (CTCA) in
      the Emergency Department (ED). Recently, three prominent trials using this
      technology in the ED setting have presented results in support of its routine
      use. However, these studies fail to show the incremental prognostic value of CTCA
      over clinical and biomarker-based risk-stratification strategies, demonstrate
      additional downstream costs and interventions, and result in multiple harms
      associated with radio-contrast and radiation exposure. Observing the widespread
      overdiagnosis of pulmonary embolism following availability of CT pulmonary
      angiogram as a practice pattern parallel, CTCA use for low-risk chest pain in the
      ED should be advanced only with caution. 

PMID- 23139095
TI  - Copeptin in acute chest pain: identification of acute coronary syndrome and
      obstructive coronary artery disease on coronary CT angiography.
AB  - OBJECTIVE: To determine the diagnostic accuracy of copeptin in patients with
      suspected acute coronary syndrome (ACS) and its correlation with obstructive
      coronary artery disease (CAD) on coronary CT angiography (CTA). METHODS: Copeptin
      was measured at arrival in 65 consecutive patients (56 +/- 10 years, 45 men)
      suspected of ACS and no indication for immediate invasive angiography. All
      patients underwent coronary CTA without disclosure of the results to the treating
      physician, and outcomes were classified as obstructive CAD (>50% stenosis) or no
      obstructive CAD (<= 50%) in one or more vessel. RESULTS: The final diagnosis of
      ACS was established in 10 (15%) patients, 6 myocardial infarctions and 4 unstable
      angina pectoris. Coronary CTA detected obstructive CAD in all patients with ACS
      and in 10 (15%) patients with no ACS. Copeptin concentrations were higher in
      patients with ACS (median 7.42 pmol/l (IQR 3.71-18.72)) vs patients with no ACS
      (3.40 pmol/l (1.13-6.27), p=0.02). Copeptin was not higher in patients with
      obstructive CAD on coronary CTA (4.87 pmol/l (2.90-8.51) vs 3.60 pmol/l (1.21
      6.23), p=0.20) compared with patients with no obstructive CAD. CONCLUSIONS:
      Copeptin seems to be elevated in patients with ACS while there is no strong
      correlation with obstructive coronary disease on CTA.

PMID- 23139096
TI  - Identifying older people at high risk of future falls: development and validation
      of a screening tool for use in emergency departments.
AB  - BACKGROUND: Hospital emergency departments (EDs) treat a high proportion of older
      people, many as a direct consequence of falling. OBJECTIVE: To develop and
      externally validate a fall risk screening tool for use in hospital EDs and to
      compare the tool's predictive ability to existing screening tools. METHODS: This
      prospective cohort study involved two hospital EDs in Sydney, Australia.
      Potential participants were people aged 70+ years who presented to the ED after
      falling or with a history of 2+ falls in the previous year and were subsequently
      discharged. 219 people participated in the tool development study and 178 people
      participated in the external validation study. Study measures included number of
      fallers during the 6-month follow-up period, and physical status, medical
      history, fall history and community service use. RESULTS: 31% and 35% of
      participants fell in the development and external validation samples,
      respectively. The developed two-item screening tool included: 2+ falls in the
      past year (OR 4.18, 95% CI 2.61 to 6.68) and taking 6+ medications (OR 1.89, CI
      1.18 to 3.04). The area under the receiver operating characteristic curve (AUC)
      was 0.70 (0.64-0.76). This represents significantly better predictive ability
      than the measure of 2+ previous falls alone (AUC 0.67, 0.62-0.72, p=0.02) and
      similar predictive ability to the FROP-Com (AUC 0.73, 0.67-0.79, p=0.25) and
      PROFET screens (AUC 0.70, 0.62-0.78, p=0.5). CONCLUSIONS: A simple, two-item
      screening tool demonstrated good external validity and accurately discriminated
      between fallers and non-fallers. This tool could identify high risk individuals
      who may benefit from onward referral or intervention after ED discharge.

PMID- 23139097
TI  - An alternative way ahead.

PMID- 23139098
TI  - Effect of paralytic type on time to post-intubation sedative use in the emergency
      department.
AB  - OBJECTIVE: To determine the difference between rocuronium and succinylcholine
      with regard to post-intubation sedative initiation in the emergency department.
      METHDS: This was a retrospective cohort study conducted in a tertiary care
      emergency department (ED) in the USA. Consecutive adult patients intubated in the
      ED using succinylcholine or rocuronium for paralysis were included. Data
      collected included patient demographics, vital signs, medications used post
      intubation and times of drug administration. Patients were divided into two
      groups based on the type of paralytic used for rapid sequence intubation: (1)
      rocuronium or (2) succinylcholine. All patients received etomidate for induction
      of sedation. Time between intubation and post-intubation sedative use was
      compared between the two groups using an unpaired Student's t test. MAIN RESULTS:
      A total of 200 patients were included in the final analyses (100 patients in each
      group). There were no significant differences between the groups with regard to
      patient demographics, vital signs or other baseline characteristics. After
      intubation, 77.5% (n=155) of patients were initiated on a sedative infusion of
      propofol (n=148) or midazolam (n=7). The remaining patients received sedation as
      bolus doses only. Mean time between intubation and post-intubation sedative use
      was significantly greater in the rocuronium group compared with the
      succinylcholine group (27 min vs 15 min, respectively; p<0.001). CONCLUSIONS:
      Patients intubated with rocuronium had greater delays in post-intubation sedative
      initiation compared with succinylcholine.

PMID- 23139099
TI  - Patients' and ambulance service clinicians' experiences of prehospital care for
      acute myocardial infarction and stroke: a qualitative study.
AB  - BACKGROUND: Patients with suspected acute myocardial infarction (AMI) and stroke
      commonly present first to the ambulance service. Little is known about
      experiences of prehospital care which are important for measuring the quality of
      services for patients with AMI or stroke. AIM: We explored experiences of
      patients, who had accessed the ambulance service for AMI or stroke, and
      clinicians regularly treating patients for these conditions in the prehospital
      setting. METHOD: A qualitative research design was employed to obtain rich and
      detailed data to explore and compare participants' experiences of emergency
      prehospital care for AMI and stroke. RESULTS: We conducted 33 semistructured
      interviews with service users and clinicians and one focus group with five
      clinicians. Four main themes emerged: communication, professionalism, treatment
      of condition and the transition from home to hospital. Patients focused on both
      personal and technical skills. Technical knowledge and relational skills together
      contributed to a perception of professionalism in ambulance personnel. Patients'
      experience was enhanced when physical, emotional and social needs were attended
      to and they emphasised effective communication within the clinician-patient
      relationship to be the key. However, we found a discrepancy between paramedics'
      perceptions of patients' expectations and patients' lack of knowledge of the
      paramedic role. CONCLUSIONS: Factors that contribute to better patient experience
      are not necessarily understood in the same way by patients and clinicians. Our
      findings can contribute to the development of patient experience measures for
      prehospital care.

PMID- 23139100
TI  - Genetic and environmental influences on non-specific neck pain in early
      adolescence: a classical twin study.
AB  - BACKGROUND: Prevalence of neck pain has increased among adolescents. The origins
      of adult chronic neck pain may lie in late childhood, but for early prevention,
      more information is needed about its aetiology. We investigated the relative
      roles of genetic and environmental factors in early adolescent neck pain with a
      classic twin study. METHODS: Frequency of neck pain was assessed with a validated
      pain questionnaire in a population-based sample of nearly 1800 pairs of 11-12
      year-old Finnish twins. Twin pair similarity for neck pain was quantified by
      polychoric correlations, and variance components were estimated with biometric
      structural equation modelling. RESULTS: Prevalence of neck pain reported at least
      once monthly was 38% and at least once weekly 16%, with no significant
      differences between gender and zygosity. A greater polychoric correlation in
      liability to neck pain was found in monozygotic (0.67) than for dizygotic pairs
      (0.38), suggesting strong genetic influences. Model fitting indicated that 68%
      (95% confidence interval 62-74) of the variation in liability to neck pain could
      be attributed to genetic effects, with the remainder attributed to unshared
      environmental effects. No evidence for sex-specific genetic effects or for sex
      differences in the magnitude of genetic effects was found. CONCLUSIONS: Genetic
      and unique environmental factors seem to play the most important roles in
      liability to neck pain in early adolescence. Future research should be directed
      to identifying pathways for genetic influences on neck pain and in exploring
      effectiveness of interventions that target already identified environmental risk
      factors.

PMID- 23139102
TI  - Racial variation in vitamin D cord blood concentration in white and black male
      neonates.
AB  - AIM: The aim of this study is to evaluate racial variation in umbilical cord
      blood concentration of vitamin D and to explore its correlation with markers of
      the insulin-like growth factor axis (IGFs) and sex steroid hormones in white and
      black male neonates. METHODS: In 2004-2005, venous umbilical cord blood samples
      were collected from 75 black and 38 white male neonates, along with maternal and
      birth characteristics from two hospitals in Maryland, United States. 25
      Hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] were
      measured by radioimmunoassay and testosterone, estradiol, and sex hormone-binding
      globulin (SHBG) by immunoassay and IGF-1, IGF-2, and IGF-binding protein-3 by
      ELISA. Crude and multivariable-adjusted geometric mean concentrations were
      computed. RESULTS: Mean 25(OH)D levels were lower in black than in white neonates
      (11.44; 95 % CI 10.10-12.95 ng/mL vs. 18.24; 95 % CI 15.32-21.72 ng/mL; p <
      0.0001). Black neonates were at higher risk of suboptimal vitamin D levels
      [25(OH)D < 20 ng/mL] than whites (84 vs. 63 %). 25(OH)D concentrations varied by
      season in whites but not in blacks and were significantly inversely correlated
      with mother's parity (number of live births) in blacks but not in whites. Mean
      concentration of 1,25(OH)(2)D did not differ by race. 25(OH)D and 1,25(OH)(2)D
      did not correlate with IGFs, sex steroid hormones, and SHBG. CONCLUSIONS:
      Suboptimal vitamin D levels were prevalent especially in blacks and influenced by
      mother's parity and by season. The observed vitamin D differences between black
      and white neonates warrant further evaluation of the etiology of the disparity in
      chronic diseases in adulthood.

PMID- 23139101
TI  - Th2 responses in schistosomiasis.
AB  - Schistosomiasis is caused by infection with parasitic flatworms of the genus
      Schistosoma. It is characterized by the development of strong CD4(+) T cell and B
      cell responses that, during primary infection, fail to eliminate the parasites,
      but in collaboration with cells of the innate immune system allow survival in the
      face of ongoing tissue damage caused by the lodging of parasite eggs in the liver
      and the passage of eggs across the intestinal epithelium. Mounting a tightly
      controlled Th2 response is key to this outcome, and while this type of response
      is a risk factor for the development of fibrosis, it also underpins the
      development of resistance to further infection; as such, understanding how Th2
      responses are induced and regulated in schistosomiasis remains a critical area of
      research.

PMID- 23139104
TI  - The artery of Percheron revisited: a cadaveric anatomical study.
AB  - BACKGROUND: The artery of Percheron (AOP) is a single thalamoperforating arterial
      trunk that provides bilateral supply to the paramedian thalami and the rostral
      midbrain. As this rare anatomical variant artery may be involved in endovascular
      procedures or encountered surgically during basilar terminus aneurysms, the
      present study was warranted. METHOD: Thirty-four adult (20 male and 14 female)
      formalin-fixed cadaveric brains underwent dissection of the 68 posterior cerebral
      arteries. Observations were made of the presence and the variations of the
      thalamoperforating arteries as well as the presence of the AOP. FINDINGS:
      Thalamoperforating arteries arose from the superior or posterior surfaces of the
      P1 segment at a mean of a 1.87 mm (range, 0.39-5.25 mm) distance from the basilar
      apex and entered the brain through the posterior perforated substance. The
      average number was 4.25 (range 1-9), and the mean diameter was 0.73 mm (range
      0.46-1.16 mm). Thalamoperforating arteries were classified into four different
      types according to their origin at the P1 segment: type I (bilateral multiple, n
      = 19), 55.8 %; type II (unilateral multiple, unilateral single, n = 4), 11.7 %;
      type III (bilateral single, n = 7), 20.5 %; type IV [one side with a single
      branch, the other side with no branches (the AOP), n = 4], 11.7 %. In three
      separate specimens with ruptured basilar artery aneurysms, the origin of the
      thalamoperforating arteries was incorporated not only into the posterior aspect
      of the aneurysm neck but also into the fundus. CONCLUSIONS: In about one tenth of
      cases the possibility of the presence of a single arterial trunk that supplies
      the two paramedian thalamic territories should be taken into consideration during
      treatment planning of basilar terminus aneurysms. Furthermore, our data show that
      the thalamoperforating arteries may take off from both the aneurysm neck and the
      fundus.

PMID- 23139103
TI  - Unusual clinico-pathological features in primary Hodgkin's lymphomas of the
      central nervous system.
AB  - Primary Hodgkin's lymphomas of the central nervous system (CNS) as well as
      cerebral involvement as the first manifestation of a systemic Hodgkin's disease
      are very rare. CNS involvement usually occurs in patients with advanced or
      relapsing systemic disease. Because primary CNS Hodgkin's lymphoma may present
      unexpected and sometimes misleading clinical and neuroradiological features, the
      description of unusual cases is important for expanding the awareness of this
      rare disease of the central nervous system. We describe three cases of primary
      Hodgkin's lymphoma of the CNS with peculiar features. None of the three patients
      had a previous clinical history of systemic Hodgkin disease. Case 1 and case 2
      presented an unusual localization in the cerebellar hemisphere and in the
      brainstem, respectively. The third case occurred as a temporal lesion in the
      settings of a Richter transformation of a chronic lymphocytic leukemia.

PMID- 23139106
TI  - [Volumes of care and outcomes].

PMID- 23139105
TI  - [Health and economic crisis in Italy].

PMID- 23139108
TI  - [A laboratory to overcome the babel of the electronic health archives].

PMID- 23139107
TI  - [Environmental disaster in Taranto, southern Italy: the contribution of
      epidemiology].

PMID- 23139109
TI  - [Open access, empowerment and cooperation in Public Health: the keywords of the
      NECOBELAC Project].

PMID- 23139110
TI  - [A cohort study on mortality and morbidity in the area of Taranto, Southern
      Italy].
AB  - INTRODUCTION: the area of Taranto has been investigated in several environmental
      and epidemiological studies due to the presence of many industrial plants and
      shipyards. Results from many studies showed excesses of mortality and cancer
      incidence for the entire city of Taranto, but there are no studies for different
      geographical areas of the city that take into account the important confounding
      effect of socioeconomic position. OBJECTIVE: to assess mortality and
      hospitalization rates of residents in Taranto, Statte and Massafra through a
      cohort study,with a particular focus on residents in the districts closest to the
      industrial complex, taking into account the socioeconomic position. METHODS: a
      cohort of residents during the period 1998-2010 was enrolled. Individual follow
      up for assessment of vital status at 31.01.2010 was performed using municipality
      data. The census-tract socioeconomic position level and the district of residence
      were assigned to each participant, on the basis of the geocoded addresses at the
      beginning of the follow- up. Standardized cause specific mortality/ morbidity
      rates, adjusted for age, were calculated by gender and districts of residence.
      Mortality and morbidity Hazard Ratios (HR, CI95%) were calculated by districts
      and socioeconomic position using Cox models. All models were adjusted for age and
      calendar period, and were done separately for men and women. RESULTS: 321.356
      people were enrolled in the cohort (48.9%males).Mortality/morbidity risks for
      natural cause, cancers, cardiovascular and respiratory diseases were found to be
      higher in low socioeconomic position groups compared to high ones. The analyses
      by districts have shown several excess mortality/morbidity risks for residents in
      Tamburi (Tamburi, Isola, Porta Napoli and LidoAzzurro), Borgo, Paolo VI and the
      municipality of Statte. CONCLUSIONS: The results of this study showed a
      significant relationship between socioeconomic position and health status of
      people resident in Taranto. People living in the districts closest to the
      industrial zone have higher mortality/morbidity levels compared to the rest of
      the area also taking into account the socioeconomic position.

PMID- 23139111
TI  - [Cancer incidence and mortality in the cohort of residents close to the Italian
      nuclear power plants of Borgo Sabotino and Garigliano].
AB  - INTRODUCTION: the potential health impacts due to the decommissioned Nuclear
      power plants (NPP) located in Borgo Sabotino and Garigliano in Central Italy
      (active from the early 1960s to the late 1980s) have raised several concerns.
      Brain, thyroid, breast and lung cancer and leukaemia have been associated with
      exposure to ionizing radiations, but the health effects of nuclear plants on the
      resident populations are controversial. OBJECTIVE: to evaluate whether living
      close to NPPs is associated with an increased risk of cancer incidence and
      mortality. METHODS: we defined a cohort of residents within 7 km from the NPPs
      during the period 1996-2002. Individual follow-up for vital status at 01.01.2007
      was conducted using municipality data. Gender specific Standardized Incidence and
      Mortality Ratios, adjusted for age, were calculated (SIR and SMR) using the
      regional population as reference. Each participant's address was assigned to a
      distance from the NPP on the basis of a GIS. A relative risk (RR, CI95%),
      adjusted for age and socioeconomic status, was calculated in 3 bands of
      increasing radius from the plants: 0-2, 2-4, and 4-7 km (reference group), using
      a Poisson regression model. RESULTS: the cohort was of 39,775 people, 32%of whom
      lived near (0-4 km) the NPP. No differences in mortality was found when comparing
      the cohort with the regional population; among women living within 7 km from the
      NPP, we found thyroid cancer incidence higher than expected (SIR 1.53 CI95% 1.18
      1.95). However, when the analysis was conducted on the basis of the distance from
      the NPP, we found a statistically significant increase in male mortality only for
      causes unrelated to radiation exposure (all causes, stomach cancer, and
      cardiovascular diseases). No mortality excess was observed among women living
      close to the NPPs. No statistically significant distance-related gradient was
      observed for cancer incidence both in men and women. CONCLUSIONS: living close to
      the NPP was not associated with mortality for causes related to radiation
      exposure. However, the results suggest to continue the epidemiological
      surveillance of the population.

PMID- 23139112
TI  - [Prevalence of malnutrition among institutionalized elderly subjects in Trieste,
      Northen Italy)].
AB  - AIM: to evaluate nutritional status in a representative sample of guests of
      residential homes for the elderly using the Mini Nutritional Assessment (MNA,
      Nestle(r)) and compare results with data from literature. DESIGN: cross-sectional
      study of prevalence using cluster sampling in two stages. SETTING AND
      PARTICIPANTS: the investigation focused on a sample of 420 guests of 37
      facilities for the elderly, out of 2,967 residents in 89 facilities in the
      province of Trieste. The target population was characterised by age  65 years,
      with different degrees of self-sufficiency. Data were collected during 2010. MAIN
      OUTCOME MEASURES: nutritional status as defined by the MNA (good, bad, risk of
      malnutrition). RESULTS: the prevalence of malnutrition and risk of malnutrition
      are respectively 14.1% (CI95% 10.2-18.0) and 48.6% (CI95%43.4-53.8).The
      prevalence of malnutrition is higher among people residing in facilities for non
      self-sufficient guests: 21.4%(14.9 to 27.9) versus 9.5%(4.7 to 14.3) among people
      residing in facilities for self-sufficient guests. The intracluster correlation
      coefficients (ICC) and the relative standard error (ES) for the variables "normal
      nutritional status", "risk of malnutrition " and "bad nutrition" are respectively
      0.19 (0.05); 0.02 (0.03); 0.05 (0.04). CONCLUSION: the prevalence of malnutrition
      and risk of malnutrition in residential facilities for the elderly in the
      province of Trieste is in line with the literature. The adoption of systematic
      nutritional screening, under the supervision and the support of the Prevention
      Departments, would allow a timely adoption of preventive and targeted therapeutic
      interventions.

PMID- 23139113
TI  - [Individual and health care factors, and one-year hospital readmission of elderly
      patients in Friuli Venezia Giulia, Northeastern Italy].
AB  - OBJECTIVE: we investigated both individual and health care risk factors for one
      year readmissions of medical patients in the Friuli Venezia Giulia Region,
      Northeastern Italy. DESIGN: we conducted a retrospective cohort study based on
      administrative databases. SETTING AND PARTICIPANTS: the cohort was made of all
      the patients who were admitted for any cause to non surgical wards of any
      regional or extraregional hospital and discharged from 01.01.2008 to 31.12.2009,
      excluding one-day stays, and who were 65 years of age, residing in Friuli Venezia
      Giulia upon admission, and still alive one year after discharge. MAIN OUTCOME
      MEASURES: we measured the frequency of one-year readmission or death and
      identified patient-level risk factors and Health Districts and Hospitals
      performing differently from the average. Multivariable logistic regression was
      used, accounting for data clustering. RESULTS: over 30% of the patients who were
      still alive one year after the index discharge were readmitted to hospital.
      Individual risk factors include age, comorbidity, cause of the index admission.
      Furthermore, being admitted to nursing homes or hospice after discharge is
      associated with increased risk of readmission. We identified an area of the
      region where five Districts performed worse than the average. CONCLUSION: we
      identified groups of the elderly population at high risk of poor outcomes after
      hospital discharge and a source of possible disparity in post-discharge health
      care in the Friuli Venezia Giulia region. These results are the starting point
      for further inquiries and for improvement of the regional systems of health care
      delivery.

PMID- 23139114
TI  - [The use of sensitive data in epidemiology: remarks on the difficulties when
      interpreting the Italian legislation].
AB  - In recent years, the impact of the Italian legislation on the use of personal
      data (Legislative Decree 196/2003 and successive regulations) on epidemiological
      research has highlighted the need for reaching a balance between protecting
      sensitive data and making these data available for public health purposes.
      Complying with this legislation constitutes a number of challenges in the field
      of epidemiology, especially with respect to the use for research of health data
      that have been collected for purposes other than research. Based on the
      difficulties experienced by the National Center of Epidemiology, Surveillance and
      Health Promotion of the Italian National Institute of Health, in the present work
      we aim to promote what we feel is a more rational approach to the concept of "use
      of sensitive data". In particular, we address the importance of these data for
      research, the concept of identifiability as defined in current legislation,
      informed consent, and the lawful use of the data. Given that data networks have
      been replacing static archives, it is more realistic to strive for the protection
      of data confidentiality, as opposed to performing irreversible anonymization of
      data. We also stress the role that research and health institutions should play
      in clearly communicating to law and policy makers the importance of the data
      routinely collected by healthcare facilities in performing epidemiological
      research and surveillance, stressing the invaluable impact of these activities on
      the health of the population. We also emphasize the importance of strengthening
      the concept that public health prevention also begins with epidemiological
      research and surveillance.

PMID- 23139115
TI  - [Estimate of the spatial variability of exposure to airborne pollutants in urban
      areas].
AB  - Several Italian and international studies investigated the short-term effects of
      air pollution in different geographical areas, while knowledge on the association
      between long-term exposure to pollutants and mortality due to natural causes and
      cardio are fully comprehensive at present. The spatial variability of pollutants
      within urban areas was analyzed with different modelling techniques. The aim of
      the present work is an introduction to the Land Use Regression (LUR) model, a
      promising approach to the estimation and representation of intraurban air
      pollution for epidemiological studies. Starting from the experiences available in
      the literature, a methodological framework of the procedure is presented,
      highlighting the advantages and limitations, especially in relation to the
      applicability of these models to exposure assessment of populations living in
      urban areas.

PMID- 23139116
TI  - Treatment update in small-cell lung cancer: from limited to extensive disease.
AB  - OPINION STATEMENT: Small-cell lung cancers are aggressive tumors, often
      discovered with widespread metastases that include brain involvement. For
      patients with limited-stage disease, the standard of care is platinum-doublet
      chemotherapy (often etoposide) with concurrent radiation. Concurrent
      chemoradiotherapy can be difficult when given upfront, sometimes preventing on
      time completion of later chemotherapy cycles. Recent data support giving
      concurrent chemoradiotherapy following 1 or 2 cycles of chemotherapy alone. For
      patients with extensive disease, chemotherapy alone remains the standard of care.
      For patients with limited or extensive disease who achieve clinical benefit from
      primary therapy, consideration of prophylactic cranial radiation should be made.
      Despite aggressive use of these treatments, most patients will have life
      threatening disease return, sometimes very soon after finishing treatment. For
      those patients who are candidates for additional systemic treatment, several
      single-agent options exist, such as topotecan, paclitaxel, or even consideration
      of retreating with the same initial regimen depending on how effective it was.
      All patients with SCLC should be considered for clinical trials, because this
      remains our greatest hope for finding more effective therapies.

PMID- 23139117
TI  - Blood-derived stem cells (BDSCs) plasticity: in vitro hepatic differentiation.
AB  - The limited availability of hepatic tissue suitable for the treatment of liver
      disease and drug research encourages the generation of hepatic-like cells from
      alternative sources as support for the regenerative medicine. Human blood derived
      stem cells (BDSCs) express surface markers and genes characteristic of
      pluripotent stem cells and have the ability to differentiate into different cell
      types, including tissues of endodermal origin (i.e., liver). Therefore they can
      represent a valuable source of hepatocytes for medicine. In this investigation,
      we exploited a fast hepatic differentiation protocol to generate hepatocyte-like
      cells from human BDSCs using only hepatocyte growth factor (HGF) and fibroblast
      growth factor-4 (FGF-4) as growth factors. The resulting cell population
      exhibited hepatic cell-like morphology and it was characterized with a variety of
      biological endpoint analyses. Here, we demonstrate how human BDSCs can be
      reprogrammed in hepatocyte-like cells by morphological, functional analysis,
      reverse transcriptase (RT)-PCR, and Western Blot assay. This study defines a fast
      and easy reprogramming strategy that facilitates the differentiation of human
      BDSCs along a hepatic lineage and provides a framework for a helpful source in
      the stem cells therapy and liver disorders.

PMID- 23139118
TI  - Self-assembly of aniline oligomers.
AB  - A great number of nano/microscaled morphologies have recently been prepared
      during the oxidation of aniline. At the early stage of oxidation, aniline
      oligomers are obtained, often in spectacular morphologies depending on reaction
      conditions. Herein, the flower-like hierarchical architectures assembled from
      aniline oligomers by a template-free method are reported. Their formation process
      is ascribed to the self-assembly of oligoanilines through non-covalent
      interactions, such as hydrogen bonding, hydrophobic forces, and pi-pi stacking.
      The model of directional growth is offered to explain the formation of petal-like
      objects and, subsequently, flowers. In order to investigate the chemical
      structure of the oligomers, a series of characterizations have been carried out,
      such as matrix-assisted laser desorption ionization, time-of-flight mass
      spectrometry, gas chromatography coupled with mass spectrometry analysis, X-ray
      diffraction, and UV/Vis, Fourier-transform infrared, and Raman spectroscopies.
      Based on the results of characterization methods, a formation mechanism for
      aniline oligomers and their self-assembly is proposed.

PMID- 23139119
TI  - Targeting von Willebrand factor as a novel anti-platelet therapy; application of
      ARC1779, an Anti-vWF aptamer, against thrombotic risk.
AB  - Excessive activation of platelets is a causative factor for thrombotic diseases
      such as acute coronary syndrome or stroke, and various anti-platelet drugs were
      developed. Aspirin and clopidogrel have been used as gold standards for anti
      platelet therapies, however, their clinical limitations including bleeding
      problem have increased the demand driving development of novel anti-platelet
      drugs with new targets. Among several activating pathways leading to platelet
      aggregation, the interaction between von Willebrand factor (vWF) and glycoprotein
      Ib, which mainly occurs under high shear stress in arterioles, is recently
      suggested to be a new promising target. The anti-thrombotic efficacy of anti-vWF
      agents, such as ARC1779, has been proved in several preclinical and clinical
      studies. Here, we will discuss the potential benefits of targeting vWF as a novel
      antiplatelet therapy, providing an insight into the role of vWF in increased
      thrombotic risk.

PMID- 23139120
TI  - Roles of phosphoinositides and phosphoinositides kinases in hepatitis C virus RNA
      replication.
AB  - Phosphoinositides (PIs) play an essential role in mediating key signaling
      pathways on biological membranes. Hepatitis C virus (HCV) replicates its RNA
      genome by establishing a viral replication complex (RC) on host cell membranes.
      Recently, an increasing body of literature reported that not only PIs themselves
      but also several PIs-specific kinases are required for efficient replication of
      HCV RNA genome. Especially, PI 4-kinases type III alpha, beta as well as their
      enzymatic products including phosphatidylinositol 4-phosphate (PI(4)P) and
      phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) are consistently identified
      to be host factors essential for HCV replication. In this article, the current
      state of our knowledge of PIs and PIs-specific kinases together with their roles
      in modulating HCV replication is reviewed. The effects of various PIs-specific
      kinases inhibitors on HCV replication are also highlighted, proposing them as
      promising candidate targets to which a new class of anti-HCV therapeutics can be
      envisaged.

PMID- 23139121
TI  - Sulphonamide and sulphonyl-hydrazone cyclic imide derivatives: antinociceptive
      activity, molecular modeling and in silico ADMET screening.
AB  - In this paper, we describe the antinociceptive activity, molecular modeling and
      in silico ADMET screening of a series of sulphonyl-hydrazone and sulphonamide
      imidobenzene derivatives. Among these compounds, the sulphonyl-hydrazones 9 and
      11 showed the most potent analgesic activity (ID(50) = 5.1 and 6.8 MUmol/kg,
      respectively). Interestingly, all derivatives evaluated in this study have a
      better analgesic profile than the control drugs, acetyl salicylic acid and
      acetaminophen. Derivative 9 was the most promising compound; with a level of
      activity that was 24 times higher than the control drugs. Our SAR study showed a
      relationship among the distribution of the frontier orbital HOMO coefficients,
      HOMO-LUMO energy gap of these molecules and their reactivity. The best analgesic
      compounds (including 6, 9, 10, 11 and 12) fulfilled the Lipinski "rule-of-five",
      which is theoretically important for good drug absorption and permeation.

PMID- 23139122
TI  - Synthesis and antitumor activity of novel diaryl ether hydroxamic acids
      derivatives as potential HDAC inhibitors.
AB  - A series of diaryl ether hydroxamic acids were synthesized for the first time and
      evaluated for the HDAC biology and antiproliferative activity. The structures of
      these new hydroxamic acids derivatives were confirmed by IR, (1)H-NMR and mass
      spectrum. Some of these compounds showed micro molar activity in the HDAC
      inhibitory assay and against four cancer cell lines.

PMID- 23139123
TI  - Benzophenone and xanthone derivatives from the inflorescences of Garcinia cowa.
AB  - The purification of the acetone extract from the inflorescences of Garcinia cowa
      led to the isolation of a new benzophenone derivative, cowanone (1), together
      with seven known xanthones, alpha-mangostin (2), beta-mangostin (3), cowanin (4),
      fuscaxanthone A (5), 9-hydroxycalabaxanthone (6), garcinianone A (7) and cowanol
      (8). The structures of the isolated compounds were elucidated by analysis of
      their spectroscopic data including 1D and 2D NMR data. All isolated compounds
      were evaluated for their antibacterial activities against Staphylococcus aureus
      (SA) and methicillin-resistant S. aureus (MRSA).

PMID- 23139124
TI  - Phenylpropanoids and lignanoids from Euonymus acanthocarpus.
AB  - A new phenylpropanoid derivative (1), along with five phenylpropanoids (2-6), two
      monoepoxy lignans (8-9), one bisepoxy lignan (10), two cyclolignans (11-12), six
      neolignans (7, 13-17), two mixed lignan-neolignans (18-19), two lignan glycosides
      (20-21), and four flavonolignans (22-25), were isolated from the stems and twigs
      of Euonymus acanthocarpus. Compounds 2-3, 6-8, 12, and 14-25 were obtained from
      Celastraceae family for the first time, and compounds 5 and 9 were isolated from
      Euonymus genus for the first time. All the compounds were tested for cytotoxicity
      against SK-OV-3 and MCG-803 human tumor cell lines. Compounds 3, 10, 12, and 18
      showed weak cytotoxicity against SK-OV-3 cell line, and compounds 3-4, 10-13, and
      19 showed weak cytotoxicity against MCG-803 cell line.

PMID- 23139125
TI  - Bioactive anthraquinones from endophytic fungus Aspergillus versicolor isolated
      from red sea algae.
AB  - The marine fungus Aspergillus versicolor was isolated from the inner tissue of
      the Red Sea green alga Halimeda opuntia. The fungus was identified by its
      morphology and 18s rDNA. Cultivation of this fungal strain led to a new
      metabolite named isorhodoptilometrin-1-methyl ether (1) along with the known
      compounds emodin (2), 1-methyl emodin (3), evariquinone (4), 7-hydroxyemodin 6,8
      methyl ether (5), siderin (6), arugosin C (7), and variculanol (8). The
      structures were elucidated on the basis of NMR spectroscopic analysis and mass
      spectrometry. The biological properties of ethyl acetate extract and compounds 1
      3 and 6-8 were explored for antimicrobial activity, anti-cancer activity and
      inhibition of Hepatitis C virus (HCV) protease.

PMID- 23139126
TI  - Decumbenone C, a new cytotoxic decaline derivative from the marine fungus
      Aspergillus sulphureus KMM 4640.
AB  - A new decaline derivative, decumbenone C (1) along with four known compounds,
      decumbenones A (2) and B (3), diorcinol (4), and brevianamide F (5) were isolated
      from the marine fungus Aspergillus sulphureus KMM 4640. Decumbenone C shows
      potent cytotoxic activity against SK-MEL-5 human melanoma cells with IC(50)
      values of 0.9 MUM.

PMID- 23139127
TI  - Inhibition of LFA-1/ICAM-1-mediated cell adhesion by stilbene derivatives from
      Rheum undulatum.
AB  - Six stilbenes were isolated from the methanol extract of Rheum undulatum rhizomes
      by bioactivity-guided fractionation. The structures of the compounds were
      determined by spectroscopic analysis ((1)H-, (13)C-NMR and MS), to be
      desoxyrhapontigenin (1), rhapontigenin (2), trans-resveratrol (3), piceatannol
      (4), piceatannol-3'-O-beta-D-glucopyranoside (5) and isorhapontin (6). Compounds
      1-4 inhibited the direct binding between sICAM-1 and LFA-1 of the THP-1 cells in
      a dose-dependent manner with IC(50) values of 50.1, 25.4, 33.4 and 45.9 MUM,
      respectively. On the other hand, the other compounds 5 and 6 with a glucose
      moiety in each molecule did not show any inhibitory activity in the cell adhesion
      assay (IC(50) values of >100.0 MUM). Compounds 2, 3 and 4 also had an inhibitory
      effect on direct binding between sVCAM-1 and VLA-4 of THP-1 cells. This suggests
      that the stilbenes from Rheum undulatum rhizomes are good candidates for
      therapeutic strategies towards inflammation.

PMID- 23139128
TI  - Inhibitory activity of Aralia continentalis roots on protein tyrosine phosphatase
      1B and rat lens aldose reductase.
AB  - As part of our continuous search for compounds from natural sources that can
      treat diabetes and its diabetic complications, in the present work, we
      investigated the protein tyrosine phosphatase 1B (PTP1B) and rat lens aldose
      reductase (RLAR) inhibitory activities of the roots of Aralia continentalis. The
      methanol extract showed a potent inhibitory activity against PTP1B and RLAR.
      Among the tested fractions, the n-hexane fraction exhibited the highest PTP1B
      inhibitory activity, while the EtOAc fraction showed highest RLAR inhibitory
      activity. Bioassayguided fractionation of the active n-hexane and EtOAc soluble
      fractions resulted in the isolation of the diterpenoids; ent-pimara-8(14),15
      diene-19-oic acid (continentalic acid, 1); ent-kaur-16-en-19-oic-acid (kaurenoic
      acid, 2); ent-pimara-8(14),15-diene-19-ol (3); 7-oxo-ent-pimara-8(14),15-diene-19
      oic acid (4); 16a-hydroxy-17-isovaleroyloxy-ent-kauran-19-oic acid (5); 17
      hydroxy-entkaur-15-en-19-oic acid (6); 15a,16a-epoxy-17-hydroxy-ent-kauran-19-oic
      acid (7); 16a,17-dihydroxy-ent-kauran-19-oic acid (8); 8a-hydroxy-ent-pimara-15
      en-19-ol (9); 4-epirulopezol (10) and 4a-hydroxy-19-nor-(-)-pimara-8(14),15-diene
      (11), from the n-hexane fraction, and 4-[formy-5-(methoxymethyl)-1H-pyrrol-1-yl]
      butanoic acid (12); vanillic acid (13); 4-hydroxybenzoic acid (14);
      protocatechuic acid (15); nicotinic acid (16); aralia cerebroside (17); 5-O
      feruloly quinic acid (18) from the EtOAc fraction. Of these, compounds 12~14, 16
      and 18 were isolated from A. continentalis for the first time. Compounds 1~10
      exhibited inhibitory potential against PTP1B, while compounds 12, 17, and 18 were
      found to be active against RLAR. Taken together, these results clearly
      demonstrate that the roots of A. continentalis displayed anti-diabetic and
      antidiabetic properties, which could be further explored to develop therapeutic
      and preventive agents for the treatment of diabetes and related complications.

PMID- 23139129
TI  - Two new hemiterpene glycosides from the leaves of Ilex rotunda. Thunb.
AB  - Chromatographic separation of the 80% MeOH extract of the leaves of Ilex rotunda
      (IR) led to isolation of two new hemiterpene glycosides, tentatively named as
      rotundarpenoside A (1) and rotundarpenoside B (2), along with five known caffeoyl
      derivatives (3-7). The chemical structures of these compounds were elucidated
      using 1D/2D NMR, HR-MS, and the absolute configuration was confirmed by Mosher's
      method. In order to evaluate their anti-oxidative activities, 1,1-diphenyl-2
      picrylhydrazyl (DPPH) radical scavenging activity and xanthine oxidase superoxide
      scavenging activities (NBT) were determined.

PMID- 23139130
TI  - Qualitative and quantitative simultaneous determination of six marker compounds
      in Soshiho-tang by HPLC-DAD-ESI-MS.
AB  - Soshiho-tang, one of the herbal prescriptions, has been used in treatment of
      chronic liver disease. In this study, the efficient high-performance liquid
      chromatography coupled with diode array detection and electrospray ionization
      tandem mass spectrometry (HPLC-DAD-ESI-MS) method was developed and validated for
      simultaneous determination of six marker compounds, namely homogentisic acid,
      baicalin, glycyrrhizin, saikosaponin A, 6-gingerol and ginsenoside Rg3 in Soshiho
      tang. The analysis of six marker compounds was carried out using a C(18) column
      (SHISEIDO S-5 MUm, 4.6 mm I.D. * 250 mm) and gradient elution with water - 0.1%
      trifluoroacetic acid and acetonitrile. The analytical method was validated for
      linearity, precision and accuracy. Calibration curve for six marker compounds
      showed good linear regression (r(2) > 0.9996). The limits of detection (LOD) and
      limits of quantification (LOQ) for analytes were ranged from 0.04 to 0.16 MUg/mL
      and 0.12 to 0.47 MUg/mL, respectively. The relative standard deviations (RSD%) of
      the precision test, intra- and inter-day, were less than 0.32% and 0.10%,
      respectively. All recoveries of the six marker compounds were ranged from 100.05%
      to 102.25% with RSD less than 0.63%. These results have shown that this developed
      method was efficient for the quality evaluation of Soshiho-tang.

PMID- 23139131
TI  - Hypoglycemic effects of Ganoderma lucidum polysaccharides in type 2 diabetic
      mice.
AB  - Our aims were to investigate the hypoglycemic effects and mechanisms of action of
      Ganoderma lucidum polysaccharides (GLPs) administered for 7 days in type 2
      diabetic mice. The mice were randomly divided into four groups (8 mice/group):
      normal control group, diabetic control group, low-dose GLP-treated diabetic group
      (50 mg/kg/d), and high-dose GLP-treated diabetic group (100 mg/kg/d). Diabetes
      was induced by streptozotocin injection and high-fat dietary feeding. At the end
      of the study, fasting serum glucose, insulin, body weight (BW) and epididymal
      white adipose tissue weight were measured. The hepatic mRNA levels of glycogen
      phosphorylase (GP), fructose-1,6-bisphosphatase (FBPase), phosphoenolpyruvate
      carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) genes were determined by
      real-time polymerase chain reaction. Both doses of GLPs significantly decreased
      fasting serum glucose, insulin and epididymal fat/BW ratio compared with the
      diabetic control group (p < 0.05). The hepatic mRNA levels of GP, FBPase, PEPCK
      and G6Pase were significantly lower in both GLP-treated groups compared with the
      diabetic control group. Taken together, GLPs significantly decrease fasting serum
      glucose levels in type 2 diabetic mice in a dose-dependent manner. The decreases
      in fasting serum glucose levels may be associated with decreased mRNA expression
      levels of several key enzymes involved in gluconeogenesis and/or glycogenolysis.

PMID- 23139132
TI  - In vivo prophylactic effects of oleanolic acid isolated from chloroform extract
      of Flaveria trinervia against ethanol induced liver toxicity in rats.
AB  - The prophylactic effects of oleanolic acid (OA) isolated from chloroform extract
      (CE) of Flaveria trinervia against ethanol induced liver toxicity was
      investigated using rats. CE and OA at three different doses were tested by
      administering orally to the ethanol treated animals during the last week of the 7
      weeks study. Silymarin was used as the standard reference. The substantially
      elevated serum enzymatic levels of serum glutamate oxaloacetate transaminase,
      glutamate pyruvate transaminase, alkaline phosphatase and bilirubin in ethanol
      treated animals were restored towards normalcy by treatment of CE and OA. In vivo
      antioxidant and in vitro free radical scavenging activities were also positive
      for all the three concentrations of CE and OA. However, OA at 150 mg/kg showed
      significant activity when compared to the other two doses. Biochemical
      observations in support with histopathological examinations revealed that CE and
      OA possess hepatoprotective action against ethanol induced hepatotoxicity in
      rats.

PMID- 23139133
TI  - Slow-binding inhibition of soybean lipoxygenase-1 by luteolin.
AB  - Luteolin, isolated from the seeds of Perilla frutescens (perilla seeds),
      inhibited the peroxidation of linoleic acid catalyzed by soybean lipoxygenase-1
      (EC 1.13.11.12, Type 1) with an IC(50) of 5.0 M (1.43 MUg/mL) noncompetitively.
      The progress curves for an enzyme reaction indicate that luteolin shows slow
      binding kinetics. Both the initial velocity and steady-state rate in the progress
      curve were decreased with increasing the concentration of luteolin. The kinetic
      parameters, which described the inhibition by luteolin, were evaluated by
      nonlinear regression fits.

PMID- 23139134
TI  - Effect of angiotensin II type I receptor A1166C polymorphism on benazepril action
      in hypertensive patients: a family-based association test study.
AB  - BACKGROUND: Few studies have examined the effect of the angiotensin II type I
      receptor (AT1R) A1166C polymorphism on the antihypertensive effect of the
      angiotensin-converting-enzyme inhibitor benazepril in patients with hypertension,
      and no such studies have performed analysis using the Family-Based Association
      Test (FBAT), The aim of our study was to examine the association between AT1R
      A1166C gene polymorphism and the antihypertensive effect of benazepril using the
      FBAT. METHODS AND RESULTS: A total of 864 patients (aged, 26-62 years) with
      essential hypertension were identified in an epidemiological survey and enrolled
      in this study. Blood pressure (BP) was measured before and after 16 days of
      treatment with benazepril (10 mg/day). The association between the A1166C gene
      polymorphism and the antihypertensive effect of benazepril was assessed by FBAT.
      The frequencies of alleles A and C were 95.1% and 4.9%, respectively. FBAT
      analysis revealed that the C allele was significantly associated with high
      baseline diastolic BP (Z = 2.041, p = 0.041), decreased systolic BP after
      treatment (Z = 2.549, p = 0.011), and decreased diastolic BP after treatment (Z =
      2.320, p = 0.020). CONCLUSION: Our results, determined using the FBAT, are the
      first evidence that the AT1R A1166C polymorphism may increase the
      antihypertensive effect of benazepril in patients with hypertension.

PMID- 23139135
TI  - Quantitative analysis of TRP channel genes in mouse organs.
AB  - The transient receptor potential (TRP) channel superfamily is a set of channel
      genes that mediate numerous physiological functions such as sensing irritants or
      detecting temperature changes. Despite their functions, expressional information
      on TRP channels in various organs is largely elusive. Therefore, we conducted a
      systematic quantitative comparison of each mRNA expression level of 22 mouse TRP
      channels in various organs. As a result, we found that average levels of TRP
      channel transcripts were very low reaching ~3% of the GAPDH transcript level.
      Among 22 TRP channels, TRPC1 and TRPM7 were most abundant in the majority of
      organs. In contrast, TRPV3, TRPV5, TRPV6, TRPC7, TRPM1, and TRPM5 elicited very
      low message profiles throughout the major organs. Consistent with their functions
      as molecular sensors for irritants and temperature changes, TRPV1, TRPM8 and
      TRPA1 showed exclusive expression in sensory ganglia. TRPC3 and TRPM3 were
      abundant in the sensory ganglia and brain. High levels of transcripts of TRPV2,
      TRPC6, TRPM4, and TRPM6 were observed in the lung. In addition, channel
      transcript levels were very low except TRPM7 in the liver. In summary, the
      expression profile of TRP channels in major tissues provides insight to their
      physiological functions and therefore application to new drug development.

PMID- 23139136
TI  - Pharmacokinetic interactions of clopidogrel with quercetin, telmisartan, and
      cyclosporine A in rats and dogs.
AB  - In this study, we investigated pharmacokinetic drug interactions of clopidogrel
      with P-gp inhibitors in rats and dogs. Following the oral administration of
      clopidogrel with or without the P-gp inhibitors, quercetin (250 mg/kg),
      telmisartan (8 mg/kg), and cyclosporine A (10 mg/kg), in rats and dogs, the
      plasma concentration-time profiles of clopidogrel carboxylic acid, a surrogate
      marker for the bioavailability of clopidogrel, were determined. Co-administration
      of the quercetin, telmisartan and cyclosporine A significantly increased the area
      under the curve and peak plasma concentration of clopidogrel carboxylic acid in
      rats. However, in dogs, the plasma concentrations of clopidogrel carboxylic acid
      were not considerably changed by the coadministration of three different kinds of
      P-gp inhibitors. These findings suggest potential interaction of clopidogrel with
      quercetin, telmisartan, and cyclosporine A, although there are differences
      between animal models. Follow-up clinical study is needed to explore the meaning
      of this remarkable species differences in the P-gp-mediated interaction.

PMID- 23139137
TI  - Proteomic analysis of breast cancer tissues to identify biomarker candidates by
      gel-assisted digestion and label-free quantification methods using LC-MS/MS.
AB  - This study presents a proteomic method that differentiates between matched normal
      and breast tumor tissues from ductal carcinoma in situ (DCIS) and invasive
      carcinoma from Korean women, to identify biomarker candidates and to understand
      pathogenesis of breast cancer in protein level. Proteins from tissues obtained by
      biopsy were extracted by RIPA buffer, digested by the gel-assisted method, and
      analyzed by nano-UPLC-MS/MS. From proteomic analysis based on label-free
      quantitation strategy, a non-redundant list of 298 proteins was identified from
      the normal and tumor tissues, and 244 proteins were quantified using IDEAL-Q
      software. Hierarchical clustering analysis showed two patterns classified as two
      groups, invasive carcinoma and DCIS, suggesting a difference between two
      carcinoma at the protein expression level as expected. Differentially expressed
      proteins in tumor tissues compared to the corresponding normal tissues were
      related to three biological pathways: antigen-processing and presentation,
      glycolysis/gluconeogenesis, and complement and coagulation cascades. Among them,
      the up-regulation of calreticulin (CRT) and protein disulfide isomerase A3
      (PDIA3) was confirmed by Western blot analysis. In conclusion, this study showed
      the possibility of identifying biomarker candidates for breast cancer using
      tissues and might help to understand the pathophysiology of this cancer at the
      protein level.

PMID- 23139138
TI  - Pharmacokinetics and tissue distribution of psammaplin A, a novel anticancer
      agent, in mice.
AB  - This study reports the pharmacokinetics and tissue distribution of a novel
      histone deacetylase and DNA methyltransferase inhibitor, psammaplin A (PsA), in
      mice. PsA concentrations were determined by a validated LC-MS/MS assay method
      (LLOQ 2 ng/mL). Following intravenous injection at a dose of 10 mg/kg in mice,
      PsA was rapidly eliminated, with the average half-life (t(1/2, lambdan)) of 9.9
      +/- 1.4 min and the systemic clearance (CL(s)) of 925.1 +/- 570.1 mL/min. The in
      vitro stability of PsA was determined in different tissue homogenates. The
      average degradation t(1/2) of PsA in blood, liver, kidney and lung was found
      relatively short (<= 12.8 min). Concerning the in vivo tissue distribution
      characteristics, PsA was found to be highly distributed to lung tissues, with the
      lung-to-serum partition coefficients (K(p)) ranging from 49.9 to 60.2. In
      contrast, PsA concentrations in other tissues were either comparable with or less
      than serum concentrations. The high and specific lung targeting characteristics
      indicates that PsA has the potential to be developed as a lung cancer treatment
      agent.

PMID- 23139139
TI  - Repair of mandibular defects by bone marrow stromal cells expressing the basic
      fibroblast growth factor transgene combined with multi-pore mineralized Bio-Oss.
AB  - The aim of the present study was to evaluate the effect of combining Bio-Oss with
      bone marrow stromal cells (BMSCs) transfected with the basic fibroblast growth
      factor (bFGF) gene on bone regeneration during mandibular distraction of rabbits.
      BMSCs obtained from rabbits were transfected with bFGF gene-encoding plasmids and
      proliferation rate and the differentiation marker alkaline phosphatase activity
      were measured. Following seeding into Bio-Oss collagen and 9-day culture in
      vitro, the surface morphology of the Bio-Oss was assessed using scanning electron
      microscopy analysis. Three mandibular defects were induced in the lower border of
      the bilateral mandibular ramus in each New Zealand white rabbit (total n=6).
      Three scaffolds, group A (seeded with BMSCs/bFGF), B (seeded with BMSCs/pVAX1)
      and C (cell-free), which had been cultured in vitro under standard cell culture
      conditions for 18 days, were implanted into mandibular defects under sterile
      conditions. Animals were sacrificed by anesthesia overdose 12 weeks following
      surgery and the scaffolds were extracted for bone mineral density and
      histological analyses. Results indicate that bFGF was successfully transfected
      into BMSCs. Proliferation and osteoblast differentiation of BMSCs were stimulated
      by bFGF in vitro. No differences were identified in surface morphology for Bio
      Oss loaded with variable groups of cells. At week 12 following implantation of
      Bio-Oss scaffolds, mineralization of BMSCs in Bio-Oss scaffolds was observed to
      be increased by bFGF. New bone and cartilage formation was revealed in
      hematoxylin and eosin-stained sections in Bio-Oss scaffolds and was most abundant
      in group A (BMSCs transfected with bFGF). In the current study, the bFGF gene was
      transfected into BMSCs and expressed successfully. bFGF promoted proliferation
      and differentiation of BMSCs in vitro and implantation of bFGF-expressing BMSCs
      combined with Bio-Oss enhanced new bone regeneration more effectively than
      traditional methods. 

PMID- 23139140
TI  - Trends in the incidence and outcomes of disseminated intravascular coagulation in
      critically ill patients (2004-2010): a population-based study.
AB  - BACKGROUND: The incidence and outcomes of disseminated intravascular coagulation
      (DIC) are incompletely defined. Therefore, we aimed to evaluate the trends in
      incidence and outcomes of critically ill patients with DIC. METHODS: We conducted
      a population-based, retrospective cohort study evaluating consecutively admitted
      adult (>= 18 years old) critically ill patients with DIC at the Mayo Clinic,
      Minnesota, from 2004 to 2010. DIC was diagnosed according to the International
      Society on Thrombosis and Hemostasis' overt DIC algorithm. Patients given a
      diagnosis of heparin-induced thrombocytopenia, thrombotic thrombocytopenic
      purpura, Child Pugh class C, or any known congenital or acquired coagulation
      disorders were excluded. RESULTS: Of the 8,089 Olmsted County resident ICU
      admissions, a total of 154 patients met the DIC inclusion criteria. The overall
      incidence rate of DIC/100,000 person-years decreased from 26.2 (95% CI, 17.1
      38.4) in 2004 to 18.6 (95% CI, 11.3-28.7) in 2010. The incidence rate of DIC
      increased with age in both men and women and was consistently higher in men, with
      the exception of the age group 18 to 39 years. The incidence rate/100,000 person
      years of DIC in men decreased from 41.6 (95% CI, 25.4-64.2) in 2004 to 21.2 (95%
      CI, 10.6 37.9) in 2010 (P = .01), whereas in women, it did not change
      significantly (P = .79). The case fatality rate did not change significantly
      during the study period. CONCLUSIONS: The incidence of DIC has decreased over the
      past decade, significantly in men, although the mortality rate remains the same.
      This is in agreement with trends in other critical care syndromes and could be
      attributable to improvements in health care delivery.

PMID- 23139141
TI  - A comparison of successful and failed protein interface designs highlights the
      challenges of designing buried hydrogen bonds.
AB  - The accurate design of new protein-protein interactions is a longstanding goal of
      computational protein design. However, most computationally designed interfaces
      fail to form experimentally. This investigation compares five previously
      described successful de novo interface designs with 158 failures. Both sets of
      proteins were designed with the molecular modeling program Rosetta. Designs were
      considered a success if a high-resolution crystal structure of the complex
      closely matched the design model and the equilibrium dissociation constant for
      binding was less than 10 MUM. The successes and failures represent a wide variety
      of interface types and design goals including heterodimers, homodimers, peptide
      protein interactions, one-sided designs (i.e., where only one of the proteins was
      mutated) and two-sided designs. The most striking feature of the successful
      designs is that they have fewer polar atoms at their interfaces than many of the
      failed designs. Designs that attempted to create extensive sets of interface
      spanning hydrogen bonds resulted in no detectable binding. In contrast, polar
      atoms make up more than 40% of the interface area of many natural dimers, and
      native interfaces often contain extensive hydrogen bonding networks. These
      results suggest that Rosetta may not be accurately balancing hydrogen bonding and
      electrostatic energies against desolvation penalties and that design processes
      may not include sufficient sampling to identify side chains in preordered
      conformations that can fully satisfy the hydrogen bonding potential of the
      interface.

PMID- 23139142
TI  - Mapping genetic loci for tolerance to lime-induced iron deficiency chlorosis in
      grapevine rootstocks (Vitis sp.).
AB  - Iron is essential to plants for chlorophyll formation as well as for the
      functioning of various iron-containing enzymes. Iron deficiency chlorosis is a
      wide-spread disorder of plants, in particular, of those growing on calcareous
      soils. Among the different ways to control iron deficiency problems for crops,
      plant material and especially rootstock breeding is a suitable and reliable
      method, especially for fruit trees and grapes. The aim of the experiment was to
      characterize the genetic basis of grapevine chlorosis tolerance under lime stress
      conditions. A segregating population of 138 F1 genotypes issued from an inter
      specific cross between Vitis vinifera Cabernet Sauvignon (tolerant) * V. riparia
      Gloire de Montpellier (sensitive) was developed and phenotyped both as cuttings
      and as rootstock grafted with Cabernet Sauvignon scions in pots containing non
      chlorosing and chlorosing soils. Tolerance was evaluated by chlorosis score, leaf
      chlorophyll content and growth parameters of the shoots and roots. The
      experiments were performed in 2001, 2003 and 2006. The plants analysed in 2006
      were reassessed in 2007. The most significant findings of the trial were: (a) the
      soil properties strongly affect plant development, (b) there are differences in
      tolerance among segregating genotypes when grown as cuttings or as rootstocks on
      calcareous soil, (c) calcareous conditions induced chlorosis and revealed
      quantitative trait loci (QTLs) implicated in polygenic control of tolerance, (d)
      rootstock strongly contributes to lime-induced chlorosis response, and (e) a QTL
      with strong effect (from 10 to 25 % of the chlorotic symptom variance) was
      identified on chromosome 13. This QTL colocalized with a QTL for chlorophyll
      content (R (2) = 22 %) and a major QTL for plant development that explains about
      50 % of both aerial and root system biomass variation. These findings were
      supported by stable results among the different years of experiment. These
      results open new insights into the genetic control of chlorosis tolerance and
      could aid the development of iron chlorosis-tolerant rootstocks.

PMID- 23139143
TI  - Marker-trait associations in Virginia Tech winter barley identified using genome
      wide mapping.
AB  - Genome-wide association studies (GWAS) provide an opportunity to examine the
      genetic architecture of quantitatively inherited traits in breeding populations.
      The objectives of this study were to use GWAS to identify chromosome regions
      governing traits of importance in six-rowed winter barley (Hordeum vulgare L.)
      germplasm and to identify single-nucleotide polymorphisms (SNPs) markers that can
      be implemented in a marker-assisted breeding program. Advanced hulled and hulless
      lines (329 total) were screened using 3,072 SNPs as a part of the US. Barley
      Coordinated Agricultural Project (CAP). Phenotypic data collected over 4 years
      for agronomic and food quality traits and resistance to leaf rust (caused by
      Puccinia hordei G. Otth), powdery mildew [caused by Blumeria graminis (DC.) E.O.
      Speer f. sp. hordei Em. Marchal], net blotch (caused by Pyrenophora teres), and
      spot blotch [caused by Cochliobolus sativus (Ito and Kuribayashi) Drechsler ex
      Dastur] were analyzed with SNP genotypic data in a GWAS to determine marker-trait
      associations. Significant SNPs associated with previously described quantitative
      trait loci (QTL) or genes were identified for heading date on chromosome 3H, test
      weight on 2H, yield on 7H, grain protein on 5H, polyphenol oxidase activity on 2H
      and resistance to leaf rust on 2H and 3H, powdery mildew on 1H, 2H and 4H, net
      blotch on 5H, and spot blotch on 7H. Novel QTL also were identified for
      agronomic, quality, and disease resistance traits. These SNP-trait associations
      provide the opportunity to directly select for QTL contributing to multiple
      traits in breeding programs.

PMID- 23139144
TI  - QTL for spot blotch resistance in bread wheat line Saar co-locate to the
      biotrophic disease resistance loci Lr34 and Lr46.
AB  - Spot blotch caused by Bipolaris sorokiniana is a major disease of wheat in warm
      and humid wheat growing regions of the world including south Asian countries such
      as India, Nepal and Bangladesh. The CIMMYT bread wheat line Saar which carries
      the leaf tip necrosis (LTN)-associated rust resistance genes Lr34 and Lr46 has
      exhibited a low level of spot blotch disease in field trials conducted in Asia
      and South America. One hundred and fourteen recombinant inbred lines (RILs) of
      Avocet (Susceptible) * Saar, were evaluated along with parents in two dates of
      sowing in India for 3 years (2007-2008 to 2009-2010) to identify quantitative
      trait loci (QTL) associated with spot blotch resistance, and to determine the
      potential association of Lr34 and Lr46 with resistance to this disease. Lr34 was
      found to constitute the main locus for spot blotch resistance, and explained as
      much as 55 % of the phenotypic variation in the mean disease data across the six
      environments. Based on the large effect, the spot blotch resistance at this locus
      has been given the gene designation Sb1. Two further, minor QTL were detected in
      the sub-population of RILs not containing Lr34. The first of these was located
      about 40 cM distal to Lr34 on 7DS, and the other corresponded to Lr46 on 1BL. A
      major implication for wheat breeding is that Lr34 and Lr46, which are widely used
      in wheat breeding to improve resistance to rust diseases and powdery mildew, also
      have a beneficial effect on spot blotch.

PMID- 23139146
TI  - Energy harvesting from the obliquely aligned InN nanowire array with a surface
      electron-accumulation layer.

PMID- 23139145
TI  - Transfer RNA modifications: nature's combinatorial chemistry playground.
AB  - Following synthesis, tRNAs are peppered by numerous chemical modifications which
      may differentially affect a tRNA's structure and function. Although modifications
      affecting the business ends of a tRNA are predictably important for cell
      viability, a majority of modifications play more subtle structural roles that can
      affect tRNA stability and folding. The current trend is that modifications act in
      concert and it is in the context of the specific sequence of a given tRNA that
      they impart their differing effects. Recent developments in the modification
      field have highlighted the diversity of modifications in tRNA. From these, the
      combinatorial nature of modifications in explaining previously described
      phenotypes derived from their absence has emerged as a growing theme.

PMID- 23139147
TI  - The BMPR2 missense mutation p.K230N and pulmonary arterial hypertension.
AB  - We present a patient that is the index case of pulmonary arterial hypertension
      (PAH) in a child due to the bone morphogenetic protein type II (BMPR2) missense
      mutation p.K230N, also known as c.690A>T. Missense mutations typically have
      earlier onset and more severe disease in PAH, so pulmonologists should be aware
      of this in the evaluation of PAH in children.

PMID- 23139148
TI  - Ventromedial prefrontal cortex reactivity is altered in generalized anxiety
      disorder during fear generalization.
AB  - BACKGROUND: Fear generalization is thought to contribute to the development and
      maintenance of anxiety symptoms and accordingly has been the focus of recent
      research. Previously, we reported that in healthy individuals (N = 25) neural
      reactivity in the insula, anterior cingulate cortex (ACC), supplementary motor
      area (SMA), and caudate follow a generalization gradient with a peak response to
      a conditioned stimulus (CS) that declines with greater perceptual dissimilarity
      of generalization stimuli (GS) to the CS. In contrast, reactivity in the
      ventromedial prefrontal cortex (vmPFC), a region linked to fear inhibition,
      showed an opposite response pattern. The aim of the current study was to examine
      whether neural responses to fear generalization differ in generalized anxiety
      disorder (GAD). A second aim was to examine connectivity of primary regions
      engaged by the generalization task in the GAD group versus healthy group, using
      psychophysiological interaction analysis. METHODS: Thirty-two women diagnosed
      with GAD were scanned using the same generalization task as our healthy group.
      RESULTS: Individuals with GAD exhibited a less discriminant vmPFC response
      pattern suggestive of deficient recruitment of vmPFC during fear inhibition.
      Across participants, there was enhanced anterior insula (aINS) coupling with the
      posterior insula, ACC, SMA, and amygdala during presentation of the CS,
      consistent with a modulatory role for the aINS in the execution of fear
      responses. CONCLUSIONS: These findings suggest that deficits in fear regulation,
      rather than in the excitatory response itself, are more critical to the
      pathophysiology of GAD in the context of fear generalization.

PMID- 23139150
TI  - Assessment of left and right ventricular parameters in healthy Korean volunteers
      using cardiac magnetic resonance imaging: change in ventricular volume and
      function based on age, gender and body surface area.
AB  - The clinical utility of cardiac magnetic resonance imaging (CMR) is growing and
      is being used predominantly as a means of measuring ventricular function. The
      normal reference range of ventricular function may vary based on age, sex and
      ethnicity. At present, most CMR reference values for healthy individuals have
      been reported from Western countries. The intent of this study was to investigate
      the normal CMR reference range for left ventricular (LV) and right ventricular
      (RV) parameters in healthy Koreans. Healthy volunteers between the ages of 20-70
      years without any history of cardiovascular disease or associated risk factors
      were prospectively recruited to be a part of this study. A total of 124 patients
      were recruited for this study. Steady-state free precession pulse sequences were
      used to obtain the cine images for LV and RV volume analysis. All parameters were
      analyzed based on age and gender, and normalized to body surface area (BSA). LV
      volume, mass and cardiac output were significantly greater in males than in
      females. However, all of these parameters which are associated with BSA and
      gender differences disappeared when corrected for BSA. RV volume was less in
      females even after the data was normalized for BSA. LV and RV volumes normalized
      for BSA gradually decreased with greater age, whereas the ejection fraction
      increased with age, thus maintaining the stroke volume index and cardiac index.
      LV and RV volumes, mass and function values for a healthy population largely
      depend on BSA and should be evaluated after normalization by BSA. LV parameters
      show no difference based on gender, but RV volume is less in the female. Greater
      age is associated with less ventricular volume, suggesting the possibility of
      volume sensitivity in the elderly.

PMID- 23139149
TI  - Evaluation of the aortic and mitral valves with cardiac computed tomography and
      cardiac magnetic resonance imaging.
AB  - Cardiac computed tomography (CT) produces high-quality anatomical images of the
      cardiac valves and associated structures. Cardiac magnetic resonance imaging
      (MRI) provides images of valve morphology, and allows quantitative evaluation of
      valvular dysfunction and determination of the impact of valvular lesions on
      cardiovascular structures. Recent studies have demonstrated that cardiac CT and
      MRI are important adjuncts to echocardiography for the evaluation of aortic and
      mitral valvular heart diseases (VHDs). Radiologists should be aware of the
      technical aspects of cardiac CT and MRI that allow comprehensive assessment of
      aortic and mitral VHDs, as well as the typical imaging features of common and
      important aortic and mitral VHDs on cardiac CT and MRI.

PMID- 23139151
TI  - Ultrastructure of the male chelicerae of Hattena cometis Domrow (Acari: Gamasida:
      Ameroseiidae) functioning as gonopods.
AB  - The ultrastructure and functional adaptations of male chelicerae in Hattena
      cometis Domrow are discussed. In particular, as in many other gamasid mites,
      males of Hattena use the chelicerae, modified as gonopods, to transfer the sperm
      into the female. For such purpose, a slender process extending from the movable
      digit, the spermatodactyl, is mainly involved. The spermatodactyl is provided
      with a sperm transfer duct; in H.cometis, the dorsal surface bent and fused with
      the ventral surface forms this duct so that the spermatodactyl appears as a
      cuticular process, connected somehow with the movable digit, and folded on itself
      to delimit the sperm transfer tube. The organization and ultrastructure of the
      spermatodactyl are discussed and compared with other gamasid mites studied so
      far.

PMID- 23139152
TI  - Special section introduction: thriving in context: findings from the 4-h study of
      positive youth development.
AB  - The positive youth development perspective, a strength-based relational
      developmental systems model that focuses on mutually influential relationships
      between individuals and contexts, has been used to study thriving across the
      second decade of life. However, more attention has been paid empirically to
      identifying the features of the individual (e.g., intentional self regulation,
      hope, or purpose) or to enumerating the role of context-general ecological assets
      than to the nature of individual-context relationships linked to thriving within
      specific contexts. The goal of this special section is to provide initial
      research reports about context-specific instances of the thriving process. The
      research focuses on two contexts where many youth spend a considerable amount,
      and often the majority, of their time-school and out-of-school time sports
      activities.

PMID- 23139153
TI  - miR-197 induces epithelial-mesenchymal transition in pancreatic cancer cells by
      targeting p120 catenin.
AB  - Invasive ductal adenocarcinoma (IDA) of the pancreas manifests poor prognosis due
      to the early invasion and distant metastasis. In contrast, intraductal papillary
      mucinous adenoma or carcinoma (IPMA or IPMC) reveals better clinical outcomes.
      Various molecular mechanisms contribute to these differences but entire picture
      is still unclear. Recent researches emphasized the important role of miRNA in
      biological processes including cancer invasion and metastasis. We previously
      described that miR-126 is down-regulated in IDA compared with IPMA or IPMC, and
      miR-126 regulates the expression of invasion related molecule disintegrin and
      metalloproteinase domain-containing protein 9 (ADAM9). Assessing the difference
      of miRNA expression profiles of IDA, IPMA, and IPMC, we newly identified miR-197
      as an up-regulated miRNA specifically in IDA. Expression of miR-197 in pancreatic
      cancer cells resulted in the induction of epithelial-mesenchymal transition (EMT)
      along with the down-regulation of p120 catenin which is a putative target of miR
      197. Direct interaction between miR-197 and p120 catenin mRNA sequence was
      confirmed by 3'UTR assay, and knockdown of p120 catenin recapitulated EMT
      induction in pancreatic cancer cells. In situ hybridization of miR-197 and
      immunohistochemistry of p120 catenin showed mutually exclusive patterns
      suggesting pivotal role of miR-197 in the regulation of p120 catenin. This miR
      197/p120 catenin axis could be a novel therapeutic target.

PMID- 23139154
TI  - Characterization of atherosclerotic plaque depositions by Raman and FTIR imaging.
AB  - Spectroscopy-based imaging techniques can provide useful biochemical information
      about tissue samples. Here, we employ Raman and Fourier transform infrared (IR)
      imaging to characterize composition and constitution of atherosclerotic plaques
      of rabbits, fed with a high cholesterol diet. The results were compared with
      conventional light microscopy after staining with hematoxylin eosin, and elastica
      van Gieson. The spectral unmixing algorithm vertex component analysis was applied
      for data analysis and image reconstruction. IR microscopy allowed for
      differentiation between lipids and proteins in plaques of full aortic cross
      sections. Raman microscopy further discriminated cholesterol esters, cholesterol
      and triglycerides. FTIR and Raman images were recorded at a resolution near 20
      micrometer per pixel for a large field of view. High resolution Raman images at 1
      micrometer per pixel revealed structural details at selected regions of interest.
      The intima-media and the lipid-protein ratio were determined in five specimens
      for quantitation. These results correlate well with histopathology. The described
      method is a promising tool for easy and fast molecular imaging of
      atherosclerosis.

PMID- 23139155
TI  - [State of health of populations residing in geothermal areas of Tuscany].
AB  - OBJECTIVE: The limited scientific knowledge on relationship between exposure and
      health effects in relation to geothermal activity motivated an epidemiologic
      investigation in Tuscan geothermal area. The study aims to describe the health
      status of populations living in Tuscany municipalities where concessions for
      exploitation of geothermal resources were granted. DESIGN: This is an ecological
      study, so it is not useful to produce evidence to sustain a judgment on the cause
      effect link. The major limits of this type of study are the use of the residence
      at municipal level as a proxy of exposure to both environmental and socioeconomic
      factors and the use of aggregated data of health outcomes that can lead to the
      well-known ecological fallacy. SETTING AND PARTICIPANTS: Sixteen municipalities
      were included in the study area: eight are part of the so-called "traditional"
      geothermal area, defined as Northern Geothermal Area (NGA) and eight located in
      the Amiata Mountain defined as Southern Geothermal Area (SGA). In 2000-2006, the
      average resident population in the overall area was approximately 43,000
      inhabitants. Thirty-one geothermal power plants were active, with a production
      capacity of 811 MW, 5 of them with 88 MW located in the SGA. Statistical analyses
      on the entire geothermal area, NGA and SGA subareas, and the sixteen
      municipalities were performed. MAIN OUTCOME MEASURES: Mortality data were
      obtained from Tuscany Regional Mortality Registry for the 1971-2006 period,
      analysing 60 causes of death, of interest for population health status or
      consistent with "Project SENTIERI" criteria. Hospital discharge records of
      residents in Tuscany Region in 2004-2006, anywhere admitted to hospital, were
      analyzed considering only the main diagnosis, excluding repeated admissions for
      the same cause. The causes taken into account are the same analysed for mortality
      were considered. Age-standardized mortality rates (TSDM) and the temporal trends
      of TSDM for four periods (1971-1979, 1980-1989, 1990-1999, 2000-2006) were
      computed. Age-standardized mortality/hospitalization ratios (SMR/SHR), with and
      without adjustment for the deprivation index based on 2001 census data, were
      calculated: mortality in the years 2000-2006 and hospitalization in 2004-2006.
      The expected number of events were computed using rates of residents in
      neighbouring municipalities (municipalities included in 50 km radius circle
      centred on the study area). Bayesian estimates of mortality/hospitalization
      ratios (BMR/BHR) at municipal level only and relating maps of the Bayesian risk
      estimators were elaborated. Congenital malformations (MC) were analysed using
      data from Tuscan Registry of Birth Defect in 1992-2006 period, relative to
      outcomes of pregnancies in women resident in the municipalities of study area,
      wherever the birth or termination of pregnancy occurred. The ratio between
      observed and expected cases (O/A), with expected defined according to regional
      rate, were calculated and O/A Bayesian estimates (BMR) are showed only at
      municipal level. The low weight and the males/females ratio at birth were
      analysed using data from Tuscany Birth Certificates, covering period 2001-2007,
      excluding births occurred in facilities outside Tuscany Region. For Low birth
      weight (< 2,500 grams), very low birth weight (< 1,500 grams), low birth weight
      in women with normal gestational age or greater than 36 weeks, gestational age
      less than 36 weeks, and the frequency of males, the observed/expected ratio was
      calculated, with the expected number defined according to regional rate. RESULTS:
      ENVIRONMENTAL BACKGROUND: High levels of arsenic in drinking water distribution
      emerges as a critical element, so that several municipalities resorted to
      granting exemptions for the parameters laid down by the Legislative Decree in
      force (D.Lgs 31/01). However, during the final phase of the study, new blast
      systems activated in the SGA decreased the arsenic levels in the water supply,
      reaching values not requiring derogations, which, instead, are still effective in
      some NGA municipalities. Air quality data, from Tuscany Regional Agency for
      Environmental Protection-ARPAT, show that geothermal activities are able to
      affect air quality, especially with hydrogen sulphide in NGA, and hydrogen
      sulphide and mercury in SGA. A significant contribution to the presence of
      mercury in air is due to previous metallurgical sites. Although mercury levels
      are below WHO guideline values, in SGA nearby Siena, values were significantly
      higher than in other geothermal areas, because of power plant PC2 (turned off in
      July 2011) in Piancastagnaio municipality. The hydrogen sulphide concentration
      levels were generally lower than WHO reference values, with occasional excesses
      over guideline value for health protection (150 ug/m3 as average of the 24
      hours). Olfactory pollution was more critic with values exceeding 7-10 ug/m3
      range even in areas without geothermal plants. RESULTS: POPULATION'S HEALTH
      STATUS: This study evaluated health status of resident population in geothermal
      areas analysing geographic and temporal distribution of mortality,
      hospitalization and reproductive health outcomes (congenital malformations, low
      birth weight, sex ratio among newborns). In both geothermal areas mortality rates
      steadily declined from 1971 to 2006, in males and females, in line with the
      regional trends. In 2000-2006 period, in the overall geothermal area a
      significant mortality excess was observed for all causes among males (2,312
      deaths, 2,146 expected), but not among females, using as reference residents in
      neighbouring municipalities. The mortality excess among males was more evident
      for infectious diseases (25 deaths, 10 expected), especially tuberculosis (8
      deaths, 2 expected), for respiratory diseases (218 deaths, 170 expected), in
      particular pneumoconiosis, including deaths from silicosis (51 deaths, 14
      expected), and for nervous system diseases (72 deaths, 56 expected). Among
      females significant mortality excess for liver cirrhosis (35 deaths, 25 expected)
      emerged, while mortality from cardiovascular diseases and ischemic heart diseases
      were significantly lower than expected. In the NGA, mortality among men was lower
      than expected for all cancers (-15%), in particular for lung cancer (- 25%),
      while values significantly in excesses were observed for infectious diseases (11
      observed, 4 expected) and respiratory diseases (90 observed, 73 expected),
      expecially pneumoconiosis (20 observed, 6 expected). Among females, significant
      mortality excesses for ovarian cancer (17 observed, 10 expected) and for
      circulatory disorders of brain (170 observed, 140 expected) resulted. In the SGA,
      mortality was more critical, accounting for majority of the excesses detected in
      overall Geothermal Area. In fact, only infectious diseases and pneumoconiosis
      were detected in excess in both the geothermal areas. In the SGA, excess of
      general mortality among males (1,431 deaths; 1,245 expected) but not among
      females emerged. Even for all cancers, an excess among males (505 deaths, 419
      expected) was observed, in particular for cancer of stomach (53 deaths, 44
      expected, not statistically significant after adjusting for DI), liver (39
      deaths, 23 expected) and lung (124 deaths, 102 expected) cancer. Mortality in SGA
      was also in excess for respiratory diseases only among men (128 deaths, 97
      expected), mostly due to silicosis (31 deaths, 8 expected), although steadily
      decreasing since 1971 as observed at regional level. Also tuberculosis resulted
      in excess in SGA (7 deaths, 1 expected). Among females acute respiratory disease
      mortality was significantly in excess (41 observed, 29 expected). Temporal trend
      showed a decline from the 70s to the 90s, with a rising trend in recent years in
      line with Tuscany region. It should be considered that pneumonia was the
      commonest cause of death of acute respiratory diseases, which allow for lower
      reliability of death certificate, especially among the elderly (> 64 years).
      Among females resident in SGA a mortality excess from digestive system diseases
      was observed (72 observed, 55 expected). The hospitalization in the overall
      Geothermal Area did not show any excess for all causes and all tumours in both
      genders. Statistically significant excesses for hospital admission from stomach
      cancer among males (49 observed, 38 expected) and females (42 observed, 28
      expected), and from lymphohematopoietic tumours among females, particularly from
      lymphatic leukaemia (15 observed, 5 expected), were observed. As mortality
      analysis highlighted, also hospital admissions by geothermal areas and gender
      showed a worst picture in SGA than in NGA. In the latter, a significant excess of
      hospital admissions from all causes among females (1,357 observed, 1,284
      expected) but not among males (1,193 observed, 1,141 expected) and an excess -
      close to statistical significance - from all tumours only among females (297
      observed; 272 expected) were observed. Furthermore, statistically significant
      excesses of hospital admissions from digestive system diseases in both genders
      (M: 392 observed, 350 expected; F: 300 observed, 268 expected), from dementias
      (16 observed, 8 expected) and from lympho hematopoietic cancers among females,
      particularly from lymphatic leukaemia (9 observed, 2 expected), were observed. In
      the SGA, statistically significant excesses of hospital admissions for stomach
      cancer (M: 32 observed, 21 expected, not significant after adjusting by DI; F: 29
      observed, 18 expected), for respiratory diseases (M: 408 observed, 351 expected;
      F: 339 observed, 277 expected) and for renal failure (M: 61 observed, 41
      expected; F: 52 observed, 34 expected) were observed in both genders. (ABSTRACT
      TRUNCATED)

PMID- 23139156
TI  - Channel sialic acids limit hERG channel activity during the ventricular action
      potential.
AB  - Activity of human ether-a-go-go-related gene (hERG) 1 voltage-gated K(+) channels
      is responsible for portions of phase 2 and phase 3 repolarization of the human
      ventricular action potential. Here, we questioned whether and how physiologically
      and pathophysiologically relevant changes in surface N-glycosylation modified
      hERG channel function. Voltage-dependent hERG channel gating and activity were
      evaluated as expressed in a set of Chinese hamster ovary (CHO) cell lines under
      conditions of full glycosylation, no sialylation, no complex N-glycans, and
      following enzymatic deglycosylation of surface N-glycans. For each condition of
      reduced glycosylation, hERG channel steady-state activation and inactivation
      relationships were shifted linearly by significant depolarizing ~9 and ~18 mV,
      respectively. The hERG window current increased significantly by 50-150%, and the
      peak shifted by a depolarizing ~10 mV. There was no significant change in maximum
      hERG current density. Deglycosylated channels were significantly more active (20
      80%) than glycosylated controls during phases 2 and 3 of action potential clamp
      protocols. Simulations of hERG current and ventricular action potentials
      corroborated experimental data and predicted reduced sialylation leads to a 50-70
      ms decrease in action potential duration. The data describe a novel mechanism by
      which hERG channel gating is modulated through physiologically and
      pathophysiologically relevant changes in N-glycosylation; reduced channel
      sialylation increases hERG channel activity during the action potential, thereby
      increasing the rate of action potential repolarization.

PMID- 23139157
TI  - Long non-coding RNAs in stem cell pluripotency.
AB  - Pluripotency refers to the self-renewal of undifferentiated embryonic stem cells
      (ESCs), and is maintained by a tightly regulated gene regulatory network
      involving an intricate interplay between transcription factors and their genomic
      targets, as well as epigenetic processes that influence gene expression. Long non
      coding RNAs (lncRNAs) are newly discovered members of gene regulatory networks
      that govern a variety of cell functions. Defined as RNA transcripts larger than
      200 nucleotides, lncRNAs have little or no protein-coding capacity and have been
      shown to act via various mechanisms, and are important in a variety of biological
      functions. Recent reports have described the discovery of pluripotent lncRNAs
      involved in the maintenance and induction of stem cell pluripotency. Here, we
      discuss how lncRNAs may integrate into the pluripotency network, as well as
      prominent questions in this emerging field.

PMID- 23139158
TI  - Structural basis of fluorescence quenching in caspase activatable-GFP.
AB  - Apoptosis is critical for organismal homeostasis and a wide variety of diseases.
      Caspases are the ultimate executors of the apoptotic programmed cell death
      pathway. As caspases play such a central role in apoptosis, there is significant
      demand for technologies to monitor caspase function. We recently developed a
      caspase activatable-GFP (CA-GFP) reporter. CA-GFP is unique due to its "dark"
      state, where chromophore maturation of the GFP is inhibited by the presence of a
      C-terminal peptide. Here we show that chromophore maturation is prevented because
      CA-GFP does not fold into the robust beta-barrel of GFP until the peptide has
      been cleaved by active caspase. Both CA-GFP and GFP1-10 , a split form of GFP
      lacking the 11th strand, have similar secondary structure, different from mature
      GFP. A similar susceptibility to proteolytic digestion indicates that this shared
      structure is not the robust, fully formed GFP beta-barrel. We have developed a
      model that suggests that as CA-GFP is translated in vivo it follows the same
      folding path as wild-type GFP; however, the presence of the appended peptide does
      not allow CA-GFP to form the barrel of the fully matured GFP. CA-GFP is therefore
      held in a "pro-folding" intermediate state until the peptide is released,
      allowing it to continue folding into the mature barrel geometry. This new
      understanding of the structural basis of the dark state of the CA-GFP reporter
      will enable manipulation of this mechanism in the development of reporter systems
      for any number of cellular processes involving proteases and potentially other
      enzymes.

PMID- 23139159
TI  - Investigating the motion of diblock copolymer assemblies in ionic liquids by in
      situ electron microscopy.
AB  - The movement of individual block copolymer micelles in free-standing films of
      ionic liquids is investigated by transmission electron microscopy with the aim of
      providing an easily accessible high-resolution imaging tool for the in situ
      observation of particle movement in a liquid environment. A proof of concept and
      first studies on the behavior of individual particles in the fluid are
      demonstrated.

PMID- 23139160
TI  - Wriggling motion trajectory illusion.
AB  - In this paper, we report on a novel visual motion illusion. When hundreds of dots
      move in straight trajectories and random directions without colliding, the
      trajectories are perceived as wriggling rather than straight (Experiment 1). We
      examined the nature of this "wriggling motion trajectory illusion" via six
      separate experiments. The illusion was most pronounced when there were a large
      number of dots (Experiment 2). The illusion was independent of both the distance
      covered (Experiment 3) and the observer's eye movements (Experiment 4) as well as
      the dot types (Experiment 5). We also showed that the proximity among the moving
      dots plays a role in the illusion (Experiment 6).

PMID- 23139161
TI  - Human optokinetic nystagmus: a stochastic analysis.
AB  - Optokinetic nystagmus (OKN) is a fundamental gaze-stabilizing response found in
      almost all vertebrates, in which eye movements attempt to compensate for the
      optic flow caused by self-motion. It is an alternating sequence of slow
      compensatory eye movements made in the direction of stimulus motion and fast eye
      movements made predominantly in the opposite direction. The timing and amplitude
      of these slow phases (SPs) and quick phases (QPs) are remarkably variable, and
      the cause of this variability is poorly understood. In this study principal
      components analysis was performed on OKN data to illustrate that the variability
      in correlation matrices across individuals and recording sessions reflected
      changes in the noise in the system while the linear relationships between
      variables remained predominantly the same. Three components were found that could
      explain the variance in OKN data, and only variables from within a single cycle
      contributed highly to any given component. A linear stochastic model of OKN was
      developed based on these results that describes OKN as a triple first order
      Markov process, with three sources of noise affecting SP velocity, the QP
      trigger, and QP amplitude. This model was used to predict the degree of signal
      dependent noise in the system, the duration of the transient state of SP
      velocity, and an apparent undershoot bias to the QP target location.

PMID- 23139162
TI  - Patient self-assessment factors predictive of persistent depressive symptoms 6
      months after enrollment in collaborative care management.
AB  - BACKGROUND: Collaborative care management (CCM) is effective for improving
      depression outcomes. However, a subset of patients will still have symptoms after
      6 months. This study sought to determine whether routinely obtained baseline
      clinical, demographic, and self-assessment variables would predict which patients
      endorse persistent depressive symptoms (PDS) after 6 months. By estimating the
      relative risk associated with the patient variables, we aimed to outline the
      combinations of factors predictive of PDS after CCM enrollment. METHODS: We
      retrospectively reviewed 1,110 adult primary care patients with the diagnosis of
      major depressive disorder enrolled in a CCM program and evaluated those with PDS
      (defined as patient health questionnaire-9score >=10) 6 months after enrollment.
      RESULTS: At baseline, an increased depression severity, worsening symptoms of
      generalized anxiety, an abnormal screening on the mood disorder questionnaire
      (MDQ) and the diagnosis of recurrent episode of depression were independent
      predictors of PDS. A patient with severe, recurrent depression, an abnormal MDQ
      screen, and severe anxiety at baseline had a predicted 42.1% probability of PDS
      at 6 months. In contrast, a patient with a moderate, first episode of depression,
      normal MDQ screen, and no anxiety symptoms had a low probability of PDS at 6.6%.
      CONCLUSIONS: This study identified several patient self-assessment scores and
      clinical diagnosis that markedly predicted the probability of PDS 6 months after
      diagnosis and enrollment into CCM. Knowledge of these high-risk attributes should
      alert the clinician to monitor select patients more closely and consider altering
      therapy appropriately.

PMID- 23139163
TI  - [Health technology assessment report. Use of liquid-based cytology for cervical
      cancer precursors screening].
AB  - OBJECTIVE OF THE PROJECT: Purpose of this Report is to evaluate the impact of the
      introduction of liquid-based cytology (LBC) in cervical cancer screening in terms
      of efficacy, undesired effects, costs and implications for organisation. EFFICACY
      AND UNDESIRED EFFECTS: LBC WITH MANUAL INTERPRETATION: The estimates of cross
      sectional accuracy for high-grade intraepithelial neoplasia (CIN2 or more severe
      and CIN3 or more severe) obtained by a systematic review and meta-analysis
      published in 2008 were used. This review considered only studies in which all
      women underwent colposcopy or randomised controlled trials (RCTs) with complete
      verification of test positives. A systematic search of RCTs published thereafter
      was performed. Three RCTs were identified. One of these studies was conducted in
      6 Italian regions and was of large size (45,174 women randomised); a second one
      was conducted in another Italian region (Abruzzo) and was of smaller size (8,654
      women randomised); a third RCT was conducted in the Netherlands and was of large
      size (89,784 women randomised). No longitudinal study was available. There is
      currently no clear evidence that LBC increases the sensitivity of cytology and
      even less that its introduction increases the efficacy of cervical screening in
      preventing invasive cancers. The Italian randomised study NTCC showed a decrease
      in specificity, which was not observed in the other two RCTs available. In
      addition, the 2008 meta-analysis observed a reduction - even if minimal - in
      specificity just at the ASC-US cytological cut-off, but also a remarkable
      heterogeneity between studies. These results suggest that the effect of LBC on
      specificity is variable and plausibly related to the local style of cytology
      interpretation. There is evidence that LBC reduces the proportion of
      unsatisfactory slides, although the size of this effect varies remarkably. LBC
      WITH COMPUTER-ASSISTED INTERPRETATION: An Australian study, based on double
      testing, showed a statistically significant increase of the sensitivity for CIN2
      or more of LBC with computer-assisted interpretation vs. conventional cytology
      with manual interpretation. However, an English RCT estimated that LBC with
      computer-assisted interpretation has a lower sensitivity than LBC with manual
      interpretation. COST AND ECONOMIC EVALUATION: In the current Italian situation
      the use of liquid-based cytology for primary screening is estimated to increase
      the costs of cytological screening. Liquid-based cytology needs shorter time for
      interpretation than conventional cytology. However, in the Italian situation,
      savings obtained from this time reduction and from the decreased number of
      repeats due to unsatisfactory slides are not currently sufficient to compensate
      the cost increase due to the prices currently applied by producers and to a
      possible greater number of colposcopies caused by LBC. In any case, at current
      prices, cost is estimated to increase even when assuming a referral rate to
      colposcopy with LBC similar or slightly lower than that with conventional
      cytology. For the costs of computer-assisted interpretation of liquid-based
      cytology, readers are referred to the relative HTA report (Epidemiol Prev
      2012;36(5) Suppl 3:e1-43). ORGANISATIONAL AND ETHICAL ASPECTS: Ethical, legal and
      communication problems are judged to remain unchanged when compared to screening
      with conventional cytology. After having used the test for some time,
      interpreters prefer liquid-based to conventional cytology. Reduced time for
      interpretation makes the adoption of LBC a possible approach to deal with
      shortenings of cytology interpreters which is happening in Italy. However,
      alternative solutions, such as computer-assisted interpretation of cytology and
      the use of HPV as primary screening test, should be considered. Liquid-based
      cytology allows performing molecular tests, in particular the HPV test. This
      property allows triaging women with borderline or mild cytology by "reflex"
      molecular or immunocytochemical tests with no need to recall them. LBC sampling
      can be used also if HPV is applied as the primary screening test, allowing
      "reflex" triaging of HPV positive women by cytology with no need to recall them
      nor to take two samples, one for HPV testing and one for conventional cytology.
      This represents a remarkable advantage in terms of organization. However, costs
      are high because only 5-7% of women screened with this approach need
      interpretation of cytology. In addition, HPV testing with the Hybrid Capture
      assay on material preserved in LBC transport media needs a preliminary conversion
      phase, which limits the use of LBC for triaging HPV positive women. It is
      advisable that in the near future industry develops sampling/transport systems
      that allow performing both the HPV test and cytology or other validated triage
      tests without additional manipulations and at sustainable costs.

PMID- 23139164
TI  - Characterization of bio-oil from hydrothermal liquefaction of organic waste by
      NMR spectroscopy and FTICR mass spectrometry.
AB  - Solid wastes of organic origins are potential feedstocks for the production of
      liquid biofuels, which could be suitable alternatives to fossil fuels for the
      transport and heating sectors, as well as for industrial use. By hydrothermal
      liquefaction, the wet biomass is partially transformed into a water-immiscible,
      oil-like organic matter called bio-oil. In this study, an integrated NMR
      spectroscopy/mass spectrometry approach has been developed for the
      characterization of the hydrothermal liquefaction of bio-oil at the molecular
      level. (1)H and (13)C NMR spectroscopy were used for the identification of
      functional groups and gauging the aromatic carbon content in the mixture. GC-MS
      analysis revealed that the volatile fraction was rich in fatty acids, as well as
      in amides and esters. High-resolution Fourier-transform ion cyclotron resonance
      mass spectrometry (FTICR-MS) has been applied in a systematic way to fully
      categorize the bio-oil in terms of different classes of components, according to
      their molecular formulas. Most importantly, for the first time, by using this
      technique, and for the liquefaction bio-oil characterization in particular, FT-MS
      data have been used to develop a methodology for the determination of the
      aromatic versus aliphatic carbon and nitrogen content. It is well known that,
      because they resist hydrogenation and represent sources of polluting species,
      both aromatic molecules and nitrogen-containing species raise concerns for
      subsequent upgrading of bio-oil into a diesel-like fuel.

PMID- 23139165
TI  - Prediction of the dry-milling performance of maize hybrids through hardness
      associated properties.
AB  - BACKGROUND: The hardness of kernels determines the dry-milling processing
      performance of maize hybrids. The identification of the best maize hybrids for
      the dry-milling process requires a limited number of simple, practical and
      reliable tests that are able to predict the potential grit yield. RESULTS: A
      total of 119 samples from different genetic and environmental backgrounds,
      collected over 3 years, were analysed for coarse/fine ratio (C/F), floating test
      (FLT), protein content (PC), kernel sphericity (S), total milling energy (TME)
      and test weight (TW). The total grit yield (TGY) of each sample was obtained
      through a micromilling procedure based on the manual separation of kernel
      endosperm followed by grinding and sieving under standard operational conditions.
      The TGY was used to establish the capability of the tests to predict the dry
      milling aptitude. Single and multiple linear regression analyses were performed
      to establish equations for the prediction of TGY using C/F, FLT, PC, S, TME and
      TW as independent variables. The analyses were performed on three data sets,
      clustered year by year of the sample collection and analysis, and the resulting
      average coefficients of determination (R(2)) were compared by analysis of
      variance. C/F, FLT, TME and, to a lesser extent, TW appeared to be easy-to-use
      independent descriptors of maize dry-milling. An improved model prediction
      ability was observed when different combinations of a few physical and chemical
      properties were used as input variables. However, the models in which three or
      more variables were used did not lead to any significant improvement in TGY
      prediction compared with the smaller models. CONCLUSION: This study contributes
      towards establishing the best predictor of maize kernel aptitude to dry-milling
      processes. Of all considered data sets, a milling evaluation factor (C/F or TME)
      coupled with kernel density (measured by means of the FLT) showed the best
      predictive ability for dry-milled product yields.

PMID- 23139166
TI  - Toll-like receptor 4/nuclear factor-kappaB signaling pathway is involved in ACTG
      toxin H-mediated anti-inflammatory effect.
AB  - ACTG-toxin H (AH) originates from Alternaria sp. In this study, we explored the
      molecular mechanism underlying the anti-inflammatory properties of AH. Treatment
      with AH inhibited lipopolysaccharide (LPS)-induced interleukin-6, IL-1beta,
      inducible nitric oxide synthase, and cyclooxygenase-2 expression and nitric oxide
      production. Furthermore, AH inhibited LPS-induced P38 MAPK and Akt activation in
      RAW264.7 cells. Electrophoretic mobility shift assays (EMSAs) showed that AH
      inhibited LPS-induced nuclear factor-kappaB (NFkappaB) DNA-binding activity.
      Using transfection assay and measurement of an NFkappaB-sensitive promoter
      region, we found that transfection of toll-like receptor 4 (TLR4) increased LPS
      induced NFkappaB transcription activity in 293T cells. AH significantly blocked
      LPS-induced NFkappaB activation in TLR4-transfected cells. Taken together, our
      data indicated that anti-inflammatory properties of AH resulted from the
      inhibition of proinflammatory cytokines and enzyme production via the
      TLR4/NFkappaB signaling pathway.

PMID- 23139167
TI  - Computational biology of RNA interactions.
AB  - The biodiversity of the RNA world has been underestimated for decades. RNA
      molecules are key building blocks, sensors, and regulators of modern cells. The
      biological function of RNA molecules cannot be separated from their ability to
      bind to and interact with a wide space of chemical species, including small
      molecules, nucleic acids, and proteins. Computational chemists, physicists, and
      biologists have developed a rich tool set for modeling and predicting RNA
      interactions. These interactions are to some extent determined by the binding
      conformation of the RNA molecule. RNA binding conformations are approximated with
      often acceptable accuracy by sequence and secondary structure motifs. Secondary
      structure ensembles of a given RNA molecule can be efficiently computed in many
      relevant situations by employing a standard energy model for base pair
      interactions and dynamic programming techniques. The case of bi-molecular RNA-RNA
      interactions can be seen as an extension of this approach. However, unbiased
      transcriptome-wide scans for local RNA-RNA interactions are computationally
      challenging yet become efficient if the binding motif/mode is known and other
      external information can be used to confine the search space. Computational
      methods are less developed for proteins and small molecules, which bind to RNA
      with very high specificity. Binding descriptors of proteins are usually
      determined by in vitro high-throughput assays (e.g., microarrays or sequencing).
      Intriguingly, recent experimental advances, which are mostly based on light
      induced cross-linking of binding partners, render in vivo binding patterns
      accessible yet require new computational methods for careful data interpretation.
      The grand challenge is to model the in vivo situation where a complex interplay
      of RNA binders competes for the same target RNA molecule. Evidently,
      bioinformaticians are just catching up with the impressive pace of these
      developments.

PMID- 23139168
TI  - Justifications for caregiving in white, Asian American, and native Hawaiian
      grandparents raising grandchildren.
AB  - OBJECTIVES: Race has been found to predict justifications for caregiving in
      family caregivers for older adults. However, little is known about this
      relationship in another type of family caregiver, Grandparents Raising
      Grandchildren (GRG). This study examined relationships between race and
      justifications for caregiving in Asian American, Native Hawaiian, and White GRG.
      METHOD: A sample of 259 GRG registered as students' primary caregivers with a
      public school system completed a modified version of the 10-item Cultural
      Justifications for Caregiving (CJCG) scale. RESULTS: CJCG items did not load onto
      a single analytic factor. Two factors, custom and responsibility, emerged. Race
      was predictive of custom, with Native Hawaiian GRG having significantly higher
      scores than White or Asian American GRG. Native Hawaiian GRG also scored higher
      than Asian American, but not White, GRG on responsibility. DISCUSSION:
      Justifications for raising grandchildren appear to differ among groups based on
      racial identification. Findings elucidate cultural justification for caregiving
      in understudied GRG populations and suggest that justifications for caregiving
      are configured differently in GRG and family caregivers for older adults. Future
      studies should examine justifications for caregiving in GRG of other races.

PMID- 23139169
TI  - Crystal structure of Jararacussin-I: the highly negatively charged catalytic
      interface contributes to macromolecular selectivity in snake venom thrombin-like
      enzymes.
AB  - Snake venom serine proteinases (SVSPs) are hemostatically active toxins that
      perturb the maintenance and regulation of both the blood coagulation cascade and
      fibrinolytic feedback system at specific points, and hence, are widely used as
      tools in pharmacological and clinical diagnosis. The crystal structure of a
      thrombin-like enzyme (TLE) from Bothrops jararacussu venom (Jararacussin-I) was
      determined at 2.48 A resolution. This is the first crystal structure of a TLE and
      allows structural comparisons with both the Agkistrodon contortrix contortrix
      Protein C Activator and the Trimeresurus stejnegeri plasminogen activator.
      Despite the highly conserved overall fold, significant differences in the amino
      acid compositions and three-dimensional conformations of the loops surrounding
      the active site significantly alter the molecular topography and charge
      distribution profile of the catalytic interface. In contrast to other SVSPs, the
      catalytic interface of Jararacussin-I is highly negatively charged, which
      contributes to its unique macromolecular selectivity.

PMID- 23139170
TI  - Patterning polymer-fullerene nanocomposite thin films with light.
AB  - The stability and association of polymer-fullerene films upon thermal annealing
      depends strongly on exposure to light, even at ambient conditions. As a result,
      dewetting of nanocomposite films can be prevented and the characteristic
      lengthscales of phase separated morphologies finely tuned. Coupling
      photopatterning with either self-organization process provides a powerful route
      for the directed assembly of fullerene-based nanocomposites into functional
      "circuits".

PMID- 23139171
TI  - Accumulation and endocrine disrupting effects of the flame retardant mixture
      Firemaster(r) 550 in rats: an exploratory assessment.
AB  - Firemaster(r) 550 (FM 550), a fire-retardant mixture used in foam-based products,
      was recently identified as a common contaminant in household dust. The chemical
      structures of its principle components suggest they have endocrine disrupting
      activity, but nothing is known about their physiological effects at
      environmentally relevant exposure levels. The goal of this exploratory study was
      to evaluate accumulation, metabolism and endocrine disrupting effects of FM 550
      in rats exposed to 100 or 1000 ug/day across gestation and lactation. FM 550
      components accumulated in tissues of exposed dams and offspring and induced
      phenotypic hallmarks associated with metabolic syndrome in the offspring. Effects
      included increased serum thyroxine levels and reduced hepatic carboxylesterease
      activity in dams, and advanced female puberty, weight gain, male cardiac
      hypertrophy, and altered exploratory behaviors in offspring. Results of this
      study are the first to implicate FM 550 as an endocrine disruptor and an obesogen
      at environmentally relevant levels.

PMID- 23139172
TI  - The curious case of miRNAs in circulation: potential diagnostic biomarkers?
AB  - The pervasive occurrence of cell-free miRNAs in circulation suggests that these
      species play an emerging role as regulatory molecules in the secretory
      environment. Are these molecules released fortuitously with no clear biological
      intent? Or do they constitute a regulatory architecture that has evolved to
      modulate gene expression using the highways and byways of the circulatory system?
      The study of circulating miRNAs continues to increase our understanding of the
      regulation of genomes. The diversity of acellular miRNAs from a functional
      perspective is discussed, and in particular we explore their utility in a
      clinical setting as blood-based biomarkers for diseases.

PMID- 23139173
TI  - Iron complex with ionic tag-catalyzed olefin reduction under oxidative conditions
      -a different reaction for iron.
AB  - An iron(III) complex with ionic tags was applied to the reduction of alkenes in
      imidazolium-based ionic liquids (ILs) under oxidative conditions. The catalyst is
      very efficient to promote reactions of biomass derivatives. At least ten
      recycling reactions were performed without any loss of catalytic activity. Some
      important mechanistic insights for this new reaction are also provided based
      mostly on electrospray ionization quadrupole-time of flight mass spectrometry
      (ESI-QTOF-MS).

PMID- 23139174
TI  - [Health technology assessment report: Computer-assisted Pap test for cervical
      cancer screening].
AB  - HEALTH PROBLEM: Cervical cancer is a disease which is highly preventable by means
      of Pap test screening for the precancerous lesions, which can be easily treated.
      Furthermore, in the near future, control of the disease will be enhanced by the
      vaccination which prevents the infection of those human papillomavirus types that
      cause the vast majority of cervical cancers. The effectiveness of screening in
      drastically reducing cervical cancer incidence has been clearly demonstrated. The
      epidemiology of cervical cancer in industrialised countries is now determined
      mostly by the Pap test coverage of the female population and by the ability of
      health systems to assure appropriate follow up after an abnormal Pap test.
      TECHNOLOGY DESCRIPTION: Today there are two fully automated systems for computer
      assisted Pap test: the BD FocalPoint and the Hologic Imager. Recently, the
      Hologic Integrated Imager, a semi-automated system, was launched. The two fully
      automated systems are composed of a central scanner, where the machine examines
      the cytologic slide, and of one or more review stations, where the cytologists
      analyze the slides previously centrally scanned. The softwares used by the two
      systems identify the fields of interest so that the cytologists can look only at
      those points, automatically pointed out by the review station. Furthermore, the
      FocalPoint system classifies the slides according to their level of risk of
      containing signs of relevant lesions. Those in the upper classes--about one fifth
      of the slides--are labelled as " further review ", while those in the lower level
      of risk, i.e. slides that have such a low level of risk that they can be
      considered as negative with no human review, are labelled as " no further review
      ". The aim of computer-assisted Pap test is to reduce the time of slide
      examination and to increase productivity. Furthermore, the number of errors due
      to lack of attention may decrease. Both the systems can be applied to liquidbased
      cytology, while only the BD Focal Point can be used on conventional smears.
      BACKGROUND: Cytology screening has some critical points: there is a shortage of
      cytologists/cytotechnicians; the quality strongly depends on the experience and
      ability of the cytologist; there is a subjective component in the cytological
      diagnosis; in highly screened populations, the prevalence of lesions is very low
      and the activity of cytologists is very monotonous. On the other hand, a
      progressive shift to molecular screening using HPV-DNA test as primary screening
      test is very likely in the near future; cytology will be used as triage test,
      dramatically reducing the number of slides to process and increasing the
      prevalence of lesions in those Pap tests. OBJECTIVES: In this Report we assume
      that the diagnostic accuracy of computer-assisted Pap test is equal to the
      accuracy of manual Pap test and, consequently, that screening using computer
      assisted Pap test has the same efficacy in reducing cervical cancer incidence and
      mortality. Under this assumption, the effectiveness/ benefit/utility is the same
      for the two screening modes, i.e. the economic analysis will be a cost
      minimization study. Furthermore, the screening process is identical for the two
      modalities in all the phases except for slide interpretation. The cost
      minimization analysis will be limited to the only phase differing between the two
      modes, i.e. the study will be a differential cost analysis between a labour
      intensive strategy (traditional Pap test) and a technology-intensive strategy
      (the computer-assisted Pap test). Briefly, the objectives of this HTA Report are:
      to determine the break even point of computer-assisted Pap test systems, i.e. the
      volume of slides processed per year at which putting in place a computer-assisted
      Pap test system becomes economically convenient; to quantify the cost per Pap
      test in different scenarios according to screening centre activity volume,
      productivity of cytologist, type of cytology (conventional smear or liquid-based,
      fully automated or semi-automated computer-assisted); to analyse the computer
      assisted Pap test in the Italian context, through a survey of the centres using
      the technology, collecting data useful for the sensitivity analysis of the
      economic evaluation; to evaluate the acceptability of the technology in the
      screening services; to evaluate the organizational and financial impact of the
      computer-assisted Pap test in different scenarios; to illustrate the ideal
      organization to implement computer-assisted Pap test in terms of volume of
      activity, productivity, and human and technological resources. PHASES OF THE
      ASSESSMENT: to produce this Report, the following process was adopted:
      application to the Ministry of health for a grant " Analysis of the impact of
      professional involvement in evidence generation for the HTA process "; within
      this project, the sub-project " Cost effectiveness evaluation of the computer
      assisted Pap test in the Italian screening programmes " was financed;
      constitution of the Working Group, which included the project coordinator, the
      principal investigator, and the health economist; identification of the centres
      using the computer-assisted Pap test and which had published scientific reports
      on the subject; identification of the Consulting Committee (stakeholder), which
      included screening programmes managers, pathologists, economists, health policy
      makers, citizen organizations, and manufacturers. Once the evaluation was
      concluded, a plenary meeting with Working Group and Consulting Committee was
      held. The working group drafted the final version of this Report, which took into
      account the comments received. RESULTS AND CONCLUSIONS: the fully automated
      computer-assisted Pap test has an important financial and organizational impact
      on screening programmes. The assessment of this health technology reached the
      following conclusions: according to the survey results, after some distrust,
      cytologists accepted the use of the machine and appreciated the reduction in
      interpretation time and the reliability in identifying the fields of interest;
      from an economic point of view, the automated computer-assisted Pap test can be
      convenient only with conventional smears if the screening centre has a volume of
      more than 49,000 slides/year and the cytologist productivity increases about
      threefold. It must be highlighted that it is not sufficient to adopt the
      automated Pap test to reach such an increase in productivity; the laboratory must
      be organised or re-organised to optimise the use of the review stations and the
      person time. In the case of liquid-based cytology, the adoption of automated
      computer- assisted Pap test can only increase the costs. In fact, liquid-based
      cytology increases the cost of consumable materials but reduces the
      interpretation time, even in manual screening. Consequently, the reduction of
      human costs is smaller in the case of computer-assisted screening. Liquid-based
      cytology has other implications and advantages not linked to the use of computer
      assisted Pap test that should be taken into account and are beyond the scope of
      this Report; given that the computer-assisted Pap test reduces human costs, it
      may be more advantageous where the cost of cytologists is higher; given the
      relatively small volume of activity of screening centres in Italy, computer
      assisted Pap test may be reasonable for a network using only one central scanner
      and several remote review stations; the use of automated computer-assisted Pap
      test only for quality control in a single centre is not economically sustainable.
      In this case as well, several centres, for example at the regional level, may
      form a consortium to reach a reasonable number of slides to achieve the break
      even point. Regarding the use of a machine rather than human intelligence to
      interpret the slides, some ethical issues were initially raised, but both the
      scientific community and healthcare professionals have accepted this technology.
      The identification of fields of interest by the machine is highly reproducible,
      reducing subjectivity in the diagnostic process. The Hologic system always
      includes a check by the human eye, while the FocalPoint system identifies about
      one fifth of the slides as No Further Review. Several studies, some of which
      conducted in Italy, confirmed the reliability of this classification. There is
      still some resistance to accept the practice of No Further Review. A check of
      previous slides and clinical data can be useful to make the cytologist and the
      clinician more confident. RECOMMENDATIONS: Computer-assisted automated Pap test
      may be introduced only if there is a need to increase the volume of slides
      screened to cover the screening target population and sufficient human resources
      are not available. Switching a programme using conventional slides to automatic
      scanning can only lead to a reduction in costs if the volume of slides per year
      exceeds 49,000 slides/annum and cytologist productivity is optimised to more than
      20,000 slides per year. At a productivity of 15,000 or fewer, the automated
      computer-assisted Pap test cannot be convenient. Switching from manual screening
      with conventional slides to automatic scanning with liquid-based cytology cannot
      generate any economic saving, but the system could increase output with a given
      number of staff. The transition from manual to computer assisted automated
      screening of liquid based cytology will not generate savings and the increase in
      productivity will be lower than that of the switch from manual/conventional to
      automated/conventional. The use of biologists or pathologists as cytologists is
      more costly than the use of cytoscreeners. Given that the automated computer
      assisted Pap test reduces human resource costs, its adoption in a model using
      only biologists and pathologists for screening is more economically advantageous.
      (ABSTRACT TRUNCATED)

PMID- 23139175
TI  - Structural insight into the separate roles of inositol tetraphosphate and
      deacetylase-activating domain in activation of histone deacetylase 3.
AB  - Histone deacetylases (HDACs) repress transcription by deacetylating acetyllysines
      on specific histone tails. HDAC3 is implicated in neurodegenerative diseases,
      certain leukemias, and even in disrupting HIV-1 latency. A recent crystal
      structure of HDAC3 in complex with the deacetylase-activating domain (DAD) of its
      corepressor complex revealed an inositol tetraphosphate (IP4) molecule at the
      protein-protein interface. IP4 was shown to play an important, yet
      mechanistically ambiguous, role in the activity of HDAC3. The goal of this
      article is to explore the conformational ensemble of HDAC3 in its inactive apo
      state and in the presence of each or both of DAD and IP4. Using triplicate, 100
      ns molecular dynamic simulations, we study the apo, ternary, and intermediate DAD
      bound or IP4-bound HDAC3 states. We find that a population-shift effect is
      induced by the presence of each corepressor, and is most notable in the presence
      of both. Our results offer new insights into the change in dynamics necessary for
      the activation of HDAC3 and highlight the roles of IP4 and DAD in this process.

PMID- 23139176
TI  - Human cell responses to ionizing radiation are differentially affected by the
      expressed connexins.
AB  - In multicellular organisms, intercellular communication is essential for
      homeostatic functions and has a major role in tissue responses to stress. Here,
      we describe the effects of expression of different connexins, which form gap
      junction channels with different permeabilities, on the responses of human cells
      to ionizing radiation. Exposure of confluent HeLa cell cultures to (137)Cs gamma
      rays, 3.7 MeV alpha particles, 1000 MeV protons or 1000 MeV/u iron ions resulted
      in distinct effects when the cells expressed gap junction channels composed of
      either connexin26 (Cx26) or connexin32 (Cx32). Irradiated HeLa cells expressing
      Cx26 generally showed decreased clonogenic survival and reduced metabolic
      activity relative to parental cells lacking gap junction communication. In
      contrast, irradiated HeLa cells expressing Cx32 generally showed enhanced
      survival and greater metabolic activity relative to the control cells. The
      effects on clonogenic survival correlated more strongly with effects on metabolic
      activity than with DNA damage as assessed by micronucleus formation. The data
      also showed that the ability of a connexin to affect clonogenic survival
      following ionizing radiation can depend on the specific type of radiation.
      Together, these findings show that specific types of connexin channels are
      targets that may be exploited to enhance radiotherapeutic efficacy and to
      formulate countermeasures to the harmful effects of specific types of ionizing
      radiation.

PMID- 23139177
TI  - From graftable biphotonic chromophores to water-soluble organic nanodots for
      biophotonics: the importance of environmental effects.
AB  - The photophysical and two-photon absorption (TPA) properties of biphotonic
      chromophores with one or two phenol pendant units were studied and compared with
      that of a model biphotonic quadrupolar chromophore. A water-soluble dendritic
      structure was then synthesized by using the pendant moieties as starting points
      for the construction of dendritic branches. We show that the polarity of the
      environment significantly modulates both the fluorescence and the TPA responses
      of the different chromophoric derivatives. This extends to more subtle effects
      that involve phenol pendant moieties that were found to act as discrete solvating
      units and to modify both the photophysics and the TPA response of the
      chromophore. This demonstrates the high sensitivity of the TPA response of
      quadrupolar derivatives to minute alterations in the environment. Moreover, the
      dendritic branches were found to behave as a peculiar cybotactic environment that
      was able to tune the fluorescence and TPA response of the inner chromophore by
      creating a polar environment. This reveals a new direction for exploiting such
      effects by playing on the dendritic architecture (e.g., the nature and shape of
      the building blocks, the geometry and position of the chromophore) to modulate
      the TPA responses.

PMID- 23139179
TI  - Antigen generation and display in therapeutic antibody drug discovery -- a
      neglected but critical player.
AB  - Disease intervention by targeting a critical pathway molecule through a blocking
      antibody or interference by therapeutic proteins is currently en vogue.
      Generation of blocking antibodies or therapeutic proteins inevitably requires the
      production of recombinant proteins or cell-based immunogens. Thus, one could call
      the antigen molecule the neglected player in antibody drug discovery. The variety
      of methods available for making recombinant proteins or recombinant cell lines
      that present the target on the cell surface is extensive. These need to be
      addressed in conjunction with biochemical and biophysical quality criteria and
      the experimental application intended. Fundamentally, successful production and
      isolation of monoclonal antibodies requires optimized antigen preparation and
      presentation to the immune host. This review summarizes the most important
      aspects of antigen generation and display, enabling logical decision making to
      give rise to potent high-affinity antibodies.

PMID- 23139178
TI  - Double-effector nanoparticles: a synergistic approach to apoptotic hyperthermia.
AB  - Highly efficient apoptotic hyperthermia is achieved using a double-effector
      nanoparticle that can generate reactive oxygen species (ROS) and heat. ROS render
      cancer cells more susceptible to subsequent heat treatment, which remarkably
      increases the degree of apoptotic cell death. Xenograft tumors (100 mm(3)) in
      mice are completely eliminated within 8 days after a single mild magnetic
      hyperthermia treatment at 43  degrees C for 30 min.

PMID- 23139180
TI  - "We're Not Twenty Two Anymore." Intimacy in Long-lived Marriages.

PMID- 23139181
TI  - Colloidal WO(3) nanowires as a versatile route to prepare a photoanode for solar
      water splitting.
AB  - This work describes a synthetic method to produce a WO(3) nanowire as well as to
      prepare photoanodes by colloidal nanowire deposition. We also studied the
      influence of a nanowire phase on the photoanode performance for water splitting.
      Among the nanowires synthesized by using nonhydrolytic media, the orthorhombic
      WO(3).H(2) O nanowire produced a photoanode with excellent performance (a
      photocurrent of 1.96 mA cm(-2) at 1.23 V(RHE) ) and good photocurrent stability
      during long-term analysis (chronoamperometry test). The structural and
      photoelectrochemical characterization showed the importance of nanostructural
      features such as exposed (200), (020), and (002) facets and porosity in the WO(3)
      photoanode performance.

PMID- 23139182
TI  - Age-dependent racemization of serine residues in a human chaperone protein.
AB  - Racemization is one of the most abundant modifications in long-lived proteins. It
      has been proposed that the accumulation of such modifications over time could
      lead to changes in tissues and ultimately human age-related diseases. Serine is
      one of the main amino acids involved in racemization; however, the site of D-Ser
      in any aged protein has yet to be reported. In this study, racemization of two
      residues, Ser 59 and Ser 62, has been demonstrated in an unstructured region of
      the small heat shock protein, alphaA-crystallin. alphaA-crystallin is also the
      most abundant structural protein in the human lens. D-Ser increased linearly with
      age in normal lenses, until it accounted for approximately 35% of the Ser at both
      sites by the age of 75 years. In agreement with a possible role in human age
      related disease, levels were significantly higher in cataract lenses. It is
      likely that such prevalent age-related changes contribute to the denaturation of
      alpha-crystallin, and therefore its ability to act as a chaperone. Racemization
      of amino acids, such as serine, in flexible regions of long-lived proteins, could
      be associated with the development of human age-related conditions such as
      cataract.

PMID- 23139184
TI  - [Animal biomonitoring and micropollutants in public health--review].
AB  - The aim of the present review is to provide a picture of the current knowledge on
      animal biomonitoring and on the link between pollution and Public Health. There
      are various reasons leading to this road: the need of early detection of
      industrial pollutants, especially micropollutants that have adverse effects in
      very low concentrations: it is important to disclose the presence of these
      compounds directly or through certain molecular biomarkers in living organisms
      rather than in the natural environment, where they are often below the detection
      threshold; the need to optimize the allocation of resources: some experiences of
      biomonitoring carried out in wild animals may be useful in the identification of
      pollution sources; however, biomonitoring of domestic animals appears to be more
      feasable and effective, because they share with humans the exposure to
      pollutants. Nowadays, professionals of different disciplines such as doctors and
      biologists do not share a common set of terms and definitions in animal
      biomonitoring: this review wants to give a contribution in the consolidation of
      the current knowledge under a common language.

PMID- 23139185
TI  - [Environmental micropollutants in livestock products from Susa Valley, Piedmont].
AB  - OBJECTIVE: to describe the contamination due to dioxins and dioxin-like PCBs of
      cattle dairy and meat products in cattle herds from Susa Valley (Piedmont) since
      the second half of 2004. DESIGN: descriptive study based on a biomonitoring
      campaign on bovine bulk milk and muscle. SETTING AND PARTICIPANTS: the official
      samplings have been carried out between 2004 and 2010: the dataset refers to 99
      mass milk samples and 24 muscle samples from 51 cattle herds based in 23
      municipalities of the valley. MAIN OUTCOME MEASURES: counts and frequencies of
      samples exceeding either the maximum levels or the action levels set by the
      European legislation; moreover relative distributions of congeners (profiles)
      were considered. RESULTS: DL-PCBs showed median concentration values double when
      compared with dioxins values and a couple of congeners (2,3,4,7,8-PeCDF, 118 DL
      PCB) were particularly abundant. More than 60% of both the milk samples and herds
      exceeded the action levels with the involvement of 10 municipalities most of
      which located nearby a local steel smelter. The DL-PCB values in milk were
      associated with the distance of each herd from the steel plant. However, the
      temporal trend highlights a clear decrease of the contamination over the 2004
      2010 period, when the plant was renewed and the production levels where
      negatively impacted by the global economical crisis. CONCLUSION: the findings of
      the monitoring activity allowed the understanding of the origin and the spatio
      temporal evolution of the contamination: this knowledge may be helpful in
      orienting future controls and the risk mitigation strategies.

PMID- 23139186
TI  - [Human biomonitoring and variation of haematic parameters in a population exposed
      to PCB and dioxin near a steel plant in the lower Susa Valley].
AB  - OBJECTIVE: to evaluate the degree of exposure to PCB in a population resident in
      the lower Susa Valley and its effects on general and endocrine homeostasis.
      DESIGN, SETTING, PARTICIPANTS AND MAIN OUTCOME MEASURES: in the lower Susa Valley
      (Piedmont, Italy), there is a steel secondary casting plant (i.e. by fusion of
      scrap iron), active since the '50s. The emissions of PCB and dioxin coming from
      the furnace were found in samples of herb, pulse and ground in a preliminary
      environmental characterisation study. During 2005-2006 we run an epidemiologic
      study of biomonitoring (measuring as outcome common haematochemical parameters,
      hormonal parameters, haematic PCB) on a sample of subjects resident in the
      municipalities with higher levels of PCB and dioxin contamination (exposed
      subjects), that was compared with another sample (unexposed) of subjects residing
      in other areas of the Susa Valley. RESULTS: the final sample consisted of 244
      subjects (119 unexposed and 125 exposed), balanced by gender, age, education and
      representative of the Susa Valley population. The greater part of hormonal and
      toxic parameters showed worse values among exposed than among unexposed,
      including PCB median value (2.30 MUg/l among exposed vs. 1.90 MUg/l among
      unexposed). The difference however was not statistically significant and the
      values were lower than the population reference values (7.2 MUg/l). Haematic PCB
      values were significantly and positively correlated with age and alcohol
      consumption and not significantly with male gender. The distribution of the
      principal haematochemical parameters (hemochrome, total, LDL and HDL cholesterol,
      triglycerides, glucose, creatinine, bilirubin, transaminases, gamma
      glutamiltranspeptidase, proteine electrophoresis) showed also, on the whole,
      worse values among exposed compared to unexposed, even if the difference was not
      statistically significant for single values. CONCLUSIONS: the exposed population
      showed higher values of PCB haematic values and alterations of the hormonal and
      common heamatochemical parameters compared to unexposed population, even if
      within reference limits.

PMID- 23139187
TI  - [Beta-hexachlorocyclohexane contamination in dairy farms of the Sacco River
      Valley, Latium, Italy, 2005. A retrospective cohort study].
AB  - OBJECTIVE: in March 2005, the Italian National Monitoring System on Chemical
      Residuals in Food of Animal Origin detected levels of the pesticide beta
      hexachlorocyclohexane (beta-HCH) that were 20 times higher than the legal limit
      of 0.003 mg/kg in bulk milk from a dairy farm in the Sacco River valley. beta
      HCH, a lindane isomer and possible human carcinogen, was subsequently found in
      milk from several neighboring farms. A study was therefore undertaken to evaluate
      the extent and risk factors for contamination. DESIGN: all dairy cattle farms in
      the valley were enrolled in a retrospective cohort study and their bulk milk
      analyzed for beta-HCH. A questionnaire was administered to farmers to evaluate
      possible exposure factors. SETTING AND PARTICIPANTS: cases: dairy farms with at
      least one result indicating beta-HCH >= 0.002 mg/kg in bulk milk during the
      period april-june 2005; exposure: feeding animals on fodder cultivated in soils
      watered with and/or flooded by river water; participants: IZSLT, RMG Local Health
      Unit, FR Local Health Unit. MAIN OUTCOME MEASURES: attack rate, relative risk,
      attributable proportion among exposed. RESULTS: of 244 farms tested, 34 met the
      case definition (attack rate 14%). The exposure to fodder cultivated in soils
      watered with and/or flooded by river water was observed in 33/34 (97%) case-farms
      and in 23/210 (10.9%) of those with contamination <0.002 mg/kg in bulk milk (RR
      110.8; 95%CI 15.5- 792). Attributable proportion among exposed was more than 99%.
      CONCLUSION: fodder cultivated near a contaminated river was the main risk factor
      for beta-HCH contaminated milk. On the basis of the epidemiologic evidence and
      laboratory testing, watering local fields with river water and production of
      fodder in farms with contaminated soil was banned, and all the animals from
      positive farms were culled.

PMID- 23139189
TI  - Hydrogen transfer in SAM-mediated enzymatic radical reactions.
AB  - S-adenosylmethionine (SAM) plays an essential role in a variety of enzyme
      mediated radical reactions. One-electron reduction of SAM is currently believed
      to generate the C5'-desoxyadenosyl radical, which subsequently abstracts a
      hydrogen atom from the actual substrate in a catalytic or a non-catalytic
      fashion. Using a combination of theoretical and experimental bond dissociation
      energy (BDE) data, the energetics of these radical processes have now been
      quantified. SAM-derived radicals are found to react with their respective
      substrates in an exothermic fashion in enzymes using SAM in a stoichiometric (non
      catalytic) way. In contrast, the catalytic use of SAM appears to be linked to a
      sequence of moderately endothermic and exothermic reaction steps. The use of SAM
      in spore photoproduct lyase (SPL) appears to fit neither of these general
      categories and appears to constitute the first example of a SAM-initiated radical
      reaction propagated independently of the cofactor.

PMID- 23139188
TI  - [Epidemiologic studies on the health status of the population living in the Sacco
      River Valley].
AB  - OBIETTIVO: to analyze the health status of the population living in an area close
      to the Colleferro industrial plant. SETTING AND PARTICIPANTS: the area of the
      Sacco River Valley, Central Italy nearby Rome, has been heavily polluted over the
      years by industrial wastes deriving from the chemical industrial plant in
      Colleferro. In 2006, it was discovered that the herds of livestock were
      contaminated by beta-hexachlorocycloexane (beta-HCH, an industrial waste
      belonging, as well as lindane, to the group of hexachlorocycloexane isomers).
      MAIN OUTCOME MEASURES: the analyses of mortality and morbidity were carried out
      for the 1998-2007 period (calculation of standardized mortality ratios, SMR), and
      for the period 2003-2007 (calculation of standardized hospitalization ratios,
      SHR), respectively. The general population in the Lazio Region has been
      considered as reference. In addition, a biomonitoring study was conducted on a
      sample of the population living in 4 areas of the Sacco River Valley with
      different levels of exposure and the following persistent organic pollutants were
      measured in the blood (alpha, beta and gamma-HCH, HCB p,p'-DDT and p,p'- DDE, 6
      NDL-PCB congeners and 12 DL-PCBs, PCDDs and PCDFs), and heavy metals (Cd, Hg,
      Pb). RESULTS: cancer mortality in men was increased in the area (SMR=1.20),
      especially for specific cancer sites (stomach, larynx, lungs, pleura, myeloma);
      in women an excess of mortality from diabetes was detected (SMR=1.44). The
      analysis of morbidity indicated an excess of hospitalization for various cancers
      (larynx, myeloma) in men, for respiratory illness and asthma in both genders and
      for thyroid disease in women. The biomonitoring study found high mean
      concentration of beta-HCH (mean: 99.05 ng/g fat, SD=121.3), with higher levels in
      the population living along the river (mean=150 ng/g fat; SD=153.5), likely
      occurred through water and local food. CONCLUSION: the area of Colleferro has
      been polluted by multiple sources and the human population has been exposed to
      industrial chemicals, toxic substances in the workplace, and to the cumulative
      accumulation of organic pesticides especially through water and food.

PMID- 23139190
TI  - Synthesis of boron-substituted diaryliodonium salts and selective transformation
      into functionalized aryl boronates.
AB  - Dormant boron awaits its true destiny in diaryliodonium salts synthesized from
      aryl boronate derivatives according to two alternative general methods with
      hypervalent iodine(III) reagents and fluoroalcohol solvents: transformation of an
      aryl C-H bond and boron-iodine(III) exchange (see scheme; FG = functional group).
      The salts could be functionalized by both catalyst-free and metal-catalyzed
      reactions without loss of the boron functionality.

PMID- 23139191
TI  - Student perspectives of imaging anatomy in undergraduate medical education.
AB  - Radiological imaging is gaining relevance in the acquisition of competencies in
      clinical anatomy. The aim of this study was to evaluate the perceptions of
      medical students on teaching/learning of imaging anatomy as an integrated part of
      anatomical education. A questionnaire was designed to evaluate the perceptions of
      second-year students participating in a clinical anatomy course over three
      consecutive academic years. A principal component analysis was used to evaluate
      the dimensionality of the questionnaire. The variables were summarized using
      frequencies, mean, median, 25th percentile, 75th percentile, minimum, and
      maximum. The results demonstrated that students felt the teaching of imaging
      anatomy influenced learning in the clinical anatomy course (mean = 4.5, median =
      5.0) and subsequent clinical courses (mean = 4.4, median = 4.0). Regarding the
      imaging techniques used in the demonstration of anatomical structures, computed
      tomography (median = 5.0) and magnetic resonance imaging (median = 5.0) were
      highly rated. Students suggested the use of additional support material (37.6%)
      and favored a more practical approach. In conclusion, the results of this work
      highlight the value of imaging anatomy in learning human anatomy. Students'
      comments pointed out a need to focus teaching/learning programs toward a more
      practical rather than theoretical approach as well as a need to provide a better
      fit between sectional anatomy and clinical cases using imaging anatomy. In order
      to provide an optimal learning environment to students, it also seems important
      to create improved media material as an additional resource tool.

PMID- 23139192
TI  - Multimodal chromatography: an efficient tool in downstream processing of
      proteins.
AB  - Chromatography has become an indispensable tool for the purification of proteins.
      Since the regulatory demands on protein purity are expected to become stricter,
      the need for generating improved resins for chromatographic separations has
      increased. More advanced scientific investigations of protein structure/function
      relationships, in particular, have also been a driving force for generating more
      sophisticated chromatographic materials for protein separations. As a
      consequence, the development of alternative chromatographic strategies has been
      very rapid during the past decade and several new ligands have been designed and
      explored both in the laboratory and in large-scale industrial settings. This
      review describes some of these efforts using multimodal chromatography, where two
      or more physicochemical properties are used to enhance the specificity of the
      interactions between the protein and the ligand on the chromatographic matrix. In
      addition to experimental studies, computer modeling of ligand-protein binding has
      improved the design of ligands for protein recognition. The use of descriptors as
      well as in silico docking methods have been implemented to design multimodal
      resins in several instances.

PMID- 23139193
TI  - Dissociation kinetics of open-chain and macrocyclic gadolinium(III)
      aminopolycarboxylate complexes related to magnetic resonance imaging: catalytic
      effect of endogenous ligands.
AB  - The kinetics of the metal exchange reactions between open-chain Gd(DTPA)(2-) and
      Gd(DTPA-BMA), macrocyclic Gd(DOTA)(-) and Gd(HP-DO3A) complexes, and Cu(2+)  ions
      were investigated in the presence of endogenous citrate, phosphate, carbonate and
      histidinate ligands in the pH range 6-8 in NaCl (0.15 M) at 25  degrees C. The
      rates of the exchange reactions of Gd(DTPA)(2-) and Gd(DTPA-BMA) are independent
      of the Cu(2+) concentration in the presence of citrate and the reactions occur
      via the dissociation of Gd(3+)  complexes catalyzed by the citrate ions. The
      HCO(3)(-)/CO(3)(2-) and H(2)PO(4)(-) ions also catalyze the dissociation of
      complexes. The rates of the dissociation of Gd(DTPA-BMA), catalyzed by the
      endogenous ligands, are about two orders of magnitude higher than those of the
      Gd(DTPA)(2-). In fact near to physiological conditions the bicarbonate and
      carbonate ions show the largest catalytic effect, that significantly increase the
      dissociation rate of Gd(DTPA-BMA) and make the higher pH values (when the
      carbonate ion concentration is higher) a risk-factor for the dissociation of
      complexes in body fluids. The exchange reactions of Gd(DOTA)(-) and Gd(HP-DO3A)
      with Cu(2+) occur through the proton assisted dissociation of complexes in the pH
      range 3.5-5 and the endogenous ligands do not affect the dissociation rates of
      complexes. More insights into the interaction scheme between Gd(DTPA-BMA) and
      Gd(DTPA)(2-) and endogenous ligands have been obtained by acquiring the (13)C NMR
      spectra of the corresponding diamagnetic Y(III)-complexes, indicating the
      increase of the rates of the intramolecular rearrangements in the presence of
      carbonate and citrate ions. The herein reported results may have implications in
      the understanding of the etiology of nephrogenic systemic fibrosis, a rare
      disease that has been associated to the administration of Gd-containing agents to
      patients with impaired renal function.

PMID- 23139194
TI  - Novel activity-based probes for broad-spectrum profiling of retaining beta
      exoglucosidases in situ and in vivo.
AB  - A high-end label: Cyclophellitol aziridine-type activity-based probes allow for
      ultra-sensitive visualization of mammalian beta-glucosidases (GBA1, GBA2, GBA3,
      and LPH) as well as several non-mammalian beta-glucosidases (see picture). These
      probes offer new ways to study beta-exoglucosidases, and configurational isomers
      of the cyclophellitol aziridine core may give activity-based probes targeting
      other retaining glycosidase families.

PMID- 23139195
TI  - [Abstracts of the XXXVI AIE National Congress. October 29-21, 2012. Bari, Italy].

PMID- 23139196
TI  - Acute pancreatitis reclassified.

PMID- 23139197
TI  - Direct transformation of N,N'-methylene bisacrylamide self-assembled fibers into
      polymer microtubes via RAFT polymerization.
AB  - A novel fabrication method of polymer tubes with simple operation process and
      high yield is presented. N,N'-methylene bisacrylamide (MBA) polymer microtubes
      are fabricated via reversible addition-fragmentation chain transfer (RAFT)
      polymerization using MBA self-assembled fibers as both the template and monomer
      source. The resulting products are characterized by SEM, TEM, FTIR, and element
      analysis. The mechanical properties of the gel-like product and the MBA organogel
      are measured by rheometer. The morphology of the polymer tubes obtained via RAFT
      polymerization is compared with the sample obtained via conventional radical
      polymerization. Based on the current investigations, the fabrication mechanism of
      this method is initially proposed.

PMID- 23139198
TI  - Magnetism-tunable oligoacene dioxide diradicals: promising magnetic oligoacene
      like molecules.
AB  - Graphene oxide has attracted intense research interest recently because the
      graphene oxide synthesis route, as a promising alternative for cost-effective
      mass production of graphene, has been explored. To further study the oxidation
      process and possible mechanism and to explore applicability of the oxidized
      products, we have performed a computational study on three series of oligoacene
      dioxides, focusing on their structures and electronic properties. Taking 1,5
      dioxidized naphthalene as a starting point, three series of oligoacene dioxides
      are considered as follows: 1) middle insertion by 1-2 benzene rings; 2) single
      side expansion using 1-2 benzene rings; 3) double-side expansion using two
      benzene rings. On the basis of density functional theory and complete active
      space self-consistent field (CASSCF) calculations, we reveal that oligoacene
      dioxides in the middle insertion series have a triplet ground state, whereas
      those in the single-side expansion series and the double-side expansion series
      have open-shell broken-symmetry singlet diradical ground states except for their
      common origin naphthalene-1,5-dioxide whose ground state is triplet and which is
      also viewed as the origin of the middle insertion series. Magnetic coupling
      interactions of these oligoacene dioxides are also determined. This work should
      help people toward an atomistic understanding of the electronic structures and
      properties of possible intermediates or products and even the oxidation mechanism
      of graphene sheets, and provides a reasonable strategy of designing novel
      graphene-oxide-based magnetic materials.

PMID- 23139199
TI  - Controlled chain-scission of polybutadiene by the Schwartz hydrozirconation.
AB  - Controlled chain-scission of polybutadiene (PB), polyisoprene, and poly(styrene
      co-butadiene), induced by bis(cyclopentadienyl) zirconium hydrochloride
      (Cp(2)ZrHCl), was revealed at room temperature. The chain-scission reaction of
      linear PB was studied by means of GPC, NMR spectroscopy, and MALDI-TOF-MS. It was
      confirmed that the molecular weights of degraded products were quasi
      quantitatively controlled by Cp(2)ZrHCl loading, irrespective of the starting PB,
      whereas the microstructure of PB chains was crucial to the scission reaction. The
      hydrozirconation of model molecules indicated that the existence of an internal
      double bond in compounds with multiple double bonds was essential for chain
      cleavage. The chain-cleavage mechanism was proposed to involve hydrozirconation
      of internal double bonds in PB chains and beta-alkyl elimination. Furthermore,
      metallocene-catalyzed chain-scission by a chain-transfer reaction was developed.
      It is believed that the reported chain scission offers a promising pathway for
      end-group functionalization by chain cleavage and presents a new application of
      Schwartz's reagent.

PMID- 23139200
TI  - Kit ligand and glial-derived neurotrophic factor as alternative supplements for
      activation and development of ovine preantral follicles in vitro.
AB  - In vitro growth of preantral follicles has the potential to produce considerable
      numbers of competent oocytes for use in medicine, agriculture, and even wildlife
      conservation. The critical regulatory role of growth factors and hormones in the
      development of preantral follicles has been established. This study investigated
      the effect of glial-derived neurotropic factor (GDNF) and kit ligand (KL) on the
      in vitro development of ovine preantral follicles. Results indicated that both
      GDNF and KL significantly improved activation of primordial follicles, similar to
      co-addition of epidermal growth factor (EGF) and basic fibroblast growth factor
      (bFGF), which are commonly used for in vitro follicular development. Importantly,
      GDNF had a more profound effect on follicle health, development, and
      differentiation compared with KL alone. Furthermore, the combination of GDNF and
      KL in the presence of EGF and bFGF had a positive, synergic effect on health,
      development, and differentiation of preantral follicles, as determined by
      histological and hormonal assessments. The results of this study may provide a
      foundation for further studies that will unravel the molecular mechanisms of
      follicular development to further improve the current status of in vitro
      preantral follicle culture.

PMID- 23139201
TI  - Drosophila melanogaster as a model to characterize fungal volatile organic
      compounds.
AB  - Fungi are implicated in poor indoor air quality and may pose a potential risk
      factor for building/mold related illnesses. Fungi emit numerous volatile organic
      compounds (VOCs) as alcohols, esters, ethers, ketones, aldehydes, terpenoids,
      thiols, and their derivatives. The toxicity profile of these VOCs has never been
      explored in a model organism, which could enable the performance of high
      throughput toxicological assays and lead to a better understanding of the
      mechanism of toxicity. We have established a reductionist Drosophila melanogaster
      model to evaluate the toxicity of fungal VOCs. In this report, we assessed the
      toxicity of fungal VOCs emitted from living cultures of species in the genera,
      Trichoderma, Aspergillus, and Penicillium and observed a detrimental effect on
      larval survival. We then used chemical standards of selected fungal VOCs to
      assess their toxicity on larval and adult Drosophila. We compared the survival of
      adult flies exposed to these fungal VOCs with known industrial toxic chemicals
      (formaldehyde [37%], xylene, benzene, and toluene). Among the tested fungal VOC
      standards, the compounds with eight carbons (C8) caused greater truncation of fly
      lifespan than tested non-C8 fungal VOCs and industrial toxins. Our data validate
      the use of Drosophila melanogaster as a model with the potential to elucidate the
      mechanistic attributes of different toxic VOCs emitted by fungi and also to
      explore the potential link between reported human illnesses/symptoms and exposure
      to water damaged and mold contaminated buildings.

PMID- 23139202
TI  - Exciton states and optical properties of carbon nanotubes.
AB  - Exciton states and related optical properties of a single-walled carbon nanotube
      are reviewed, primarily from a theoretical viewpoint. The energies and
      wavefunctions of excitons are discussed using a screened Hartree-Fock
      approximation with an effective-mass or k.p approximation. The close relationship
      between a long-range electron-hole exchange interaction and a depolarization
      effect is clarified. I discuss optical properties including the radiative
      lifetime of excitons, absorption spectra and radiation force. To describe these
      properties in a unified scheme, a self-consistent method is introduced for
      calculating the scattering light and induced current density due to excitons. I
      also briefly review experimental results on the Aharonov-Bohm effect in excitons
      and quasi-dark excitons excited by light polarized perpendicular to the tube
      axis.

PMID- 23139203
TI  - oct4-EGFP reporter gene expression marks the stem cells in embryonic development
      and in adult gonads of transgenic medaka.
AB  - Maintenance of pluripotency in stem cells is tightly regulated among vertebrates.
      One of the key genes in this process is oct4, also referred to as pou5f1 in
      mammals and pou2 in teleosts. Pou5f1 evolved by duplication of pou2 early in the
      tetrapod lineage, but only monotremes and marsupials retained both genes. Either
      pou2 or pou5f1 was lost from the genomes of the other tetrapods that have been
      analyzed to date. Consequently, these two homologous genes are often designated
      oct4 in functional studies. In most vertebrates oct4 is expressed in pluripotent
      cells of the early embryo until the blastula stage, and later persist in germline
      stem cells until adulthood. The isolation and analysis of stem cells from embryo
      or adult individuals is hampered by the need for reliable markers that can
      identify and define the cell populations. Here, we report the faithful expression
      of EGFP under the control of endogenous pou2/oct4 promoters in transgenic medaka
      (Oryzias latipes). In vivo imaging in oct4-EGFP transgenic medaka reveals the
      temporal and spatial expression of pou2 in embryos and adults alike. We describe
      the temporal and spatial patterns of endogenous pou2 and oct4-EGFP expression in
      medaka with respect to germline and adult stem cells, and discuss applications of
      oct4-EGFP transgenic medaka in reproductive and stem cell biology.

PMID- 23139204
TI  - Gene expression profile in chronic mouse liver injury caused by long-term
      exposure to CeCl3.
AB  - Numerous studies have demonstrated lanthanide (Ln) accumulation in the liver, and
      the corresponding damage; however, very little work has been done to evaluate the
      relationship between Ln-induced liver injury and its gene expression profile in
      mice. In this study, liver injury and gene-expressed profiles in male mice
      induced by oral administration of CeCl3 (2 mg/kg) via gavage for 90 consecutive
      days were investigated. The results showed that cerium accumulation, liver
      inflammation, and hepatocyte necrosis were observed. CeCl3 exposure significantly
      decreased the counts of white blood cells, lymphocyte, and platelet, the
      reticulocyte count (Ret) and neutrophilic granulocyte percentages as well as A/G
      ratio, whereas markedly increased the activities of alkaline phosphatase, lactate
      dehydrogenase, and cholinesterase, and the concentrations of triglycerides and
      total cholesterol. Furthermore, microarray results of liver showed that the
      differential expression of 675 known function genes involved in
      immune/inflammation response, apoptosis, metabolic process, cell cycle, cell
      proliferation, cytoskeleton, oxidative stress, signal transduction,
      transcription, translation, and transportation in CeCl3 exposed livers,
      respectively. Specifically, the significant downregulation of Nt5e led to
      inflammation, overexpressed Cyp4a12a and great suppression of Cdkn1a resulted in
      hepatocyte apoptosis, marked elevation of Cel, and Cyp7b1 expression caused the
      metabolic disorders in mouse liver after long-term CeCl3 exposure. Therefore,
      these genes may be in great relation to liver damages induced by exposure to
      CeCl3 .

PMID- 23139205
TI  - Analysis of metabolic syndrome in adult dermatomyositis with a focus on
      cardiovascular disease.
AB  - OBJECTIVE: To evaluate the frequency of metabolic syndrome in dermatomyositis
      (DM) patients and to analyze the possible association of metabolic syndrome with
      traditional cardiovascular disease (CVD) risk factors and DM-related clinical and
      laboratory features. METHODS: The present cross-sectional single-center study
      included 84 DM patients and 105 healthy controls. Metabolic syndrome was
      diagnosed according to the National Cholesterol Education Program Adult Treatment
      Panel III. RESULTS: The median age was similar in both the DM and control groups
      (41.5 and 42.0 years, respectively; P = 0.378), with a comparable predominance of
      women (P = 0.904) and white race (P = 0.623). The DM patients had a higher
      prevalence of metabolic syndrome (41.7% versus 7.0%; P < 0.001), diabetes
      mellitus (17.9% versus 1.0%; P < 0.001), stroke (4.8% versus 0%; P = 0.024), and
      family history of CVD (23.8% versus 8.6%; P = 0.004). However, the frequency of
      sedentarism, hypothyroidism, smoking, and alcohol intake was similar in both
      groups (P > 0.05). Further analysis of the DM patients with (n = 35) and without
      (n = 49) metabolic syndrome revealed that the patients with this complication
      were older (mean +/- SD age 50.0 +/- 14.5 years versus 40.9 +/- 14.6 years; P =
      0.006) and had a similar disease duration (P = 0.925) and higher prevalence of
      systemic arterial hypertension prior to the onset of disease symptoms (54.3%
      versus 10.2%; P < 0.001). In a multivariate analysis, only hypertension diagnosed
      prior to the disease was associated with metabolic syndrome (odds ratio 10.47
      [95% confidence interval 2.62-44.81]). CONCLUSION: Metabolic syndrome is highly
      prevalent in DM, and prior hypertension seems to be a major determinant of its
      development, while disease- and therapy-related factors do not appear to play a
      relevant role.

PMID- 23139206
TI  - Influence of polarizability on metal oxide properties studied by molecular
      dynamics simulations.
AB  - We have studied the dependence of metal oxide properties in molecular dynamics
      (MD) simulations on the polarizability of oxygen ions. We present studies of both
      liquid and crystalline structures of silica (SiO(2)), magnesia (MgO) and alumina
      (Al(2)O(3)). For each of the three oxides, two separately optimized sets of force
      fields were used: (i) long-range Coulomb interactions between oxide and metal
      ions combined with a short-range pair potential; (ii) extension of force field
      (i) by adding polarizability to the oxygen ions. We show that while an effective
      potential of type (i) without polarizable oxygen ions can describe radial
      distributions and lattice constants reasonably well, potentials of type (ii) are
      required to obtain correct values for bond angles and the equation of state. The
      importance of polarizability for metal oxide properties decreases with increasing
      temperature.

PMID- 23139207
TI  - Realizing the clinical potential of cancer nanotechnology by minimizing
      toxicologic and targeted delivery concerns.
AB  - Nanotechnology has the potential to make smart drugs that would be capable of
      targeting cancer but not normal cells and to load combinations of cooperating
      agents into a single nanosized particle to more effectively treat this disease.
      However, to realize the full potential of this technology, the negative aspects
      associated with these nanoparticles need to be overcome. This review discusses
      concerns in the field limiting realization of the full clinical potential of this
      technology, which are toxicity and targeted delivery. Strategies to overcome
      these hurdles are also reviewed, which could lead to attainment of the full
      clinical potential of this exciting technology.

PMID- 23139208
TI  - Oncostatin m modulates the mesenchymal-epithelial transition of lung
      adenocarcinoma cells by a mesenchymal stem cell-mediated paracrine effect.
AB  - Mesenchymal stem cells (MSC) are strongly associated with tumor progression and
      have been used as novel cell-based agents to deliver anticancer drugs to tumors.
      However, controversies about the direct involvement of MSCs in tumor progression
      suggest that MSCs mediate tumor progression in a cancer type-dependent manner. In
      this report, we analyzed the functional interactions between human MSCs and lung
      adenocarcinoma (LAC) cells to determine the therapeutic potential of MSCs in lung
      cancer. We showed that MSCs effectively inhibited the migration, invasion, and
      cell-cycle progression of several LAC cell lines. MSCs also enhanced the
      mesenchymal-epithelial transition (MET) pathway, as evidenced by the reduction of
      several epithelial-mesenchymal transition-related markers in LAC cells cocultured
      with MSCs or in MSC-conditioned medium (MSC-CM). By cytokine array analysis, we
      determined that Oncostatin M (OSM), a differentiation-promoting cytokine, was
      elevated in the MSC-CM derived from primary MSC cultures. Furthermore, OSM
      treatment had the same effects as MSC-CM on LAC, whereas neutralizing antibodies
      to OSM reversed them. Notably, short hairpin RNAs against STAT1, an important
      downstream target of OSM, hindered the OSM-dependent induction of MET. In vivo
      xenograft tumor studies indicated that OSM inhibited tumor formation and
      metastasis of LAC cells, whereas neutralizing OSM in the MSC-CM hampered its
      inhibitory effects. In conclusion, this study showed that OSM is a paracrine
      mediator of MSC-dependent inhibition of tumorigenicity and activation of MET in
      LAC cells. These effects of OSM may serve as a basis for the development of new
      drugs and therapeutic interventions targeting cancer cells.

PMID- 23139209
TI  - FoxM1 and Wnt/beta-catenin signaling in glioma stem cells.
AB  - Cancer stem cells may be responsible for tumor initiation and maintenance. The
      molecular mechanisms that control cancer stem cells are related to alterations in
      various signaling pathways, including the Wnt/beta-catenin signaling pathway. The
      canonical Wnt/beta-catenin signaling pathway is one of the major signaling
      systems in stem and progenitor cells, and aberrant activation of the Wnt/beta
      catenin signaling pathway is common in human cancers. As with beta-catenin, FoxM1
      has been found to play important roles in a number of cancers. In this review, we
      discuss the evidence that FoxM1 affects the expression and function of a variety
      of genes that are critical to the survival, proliferation, invasion,
      angiogenesis, and self-renewal of cancer stem cells. We highlight the pivotal
      roles of the Wnt/beta-catenin and FoxM1 signaling pathways in neural stem and
      progenitor cells and glioma stem cells. We also discuss the evidence for cross
      talk between the beta-catenin and FoxM1 signaling pathways in the regulation of
      the stemness and tumorigenicity of glioma stem cells.

PMID- 23139210
TI  - An integrated genomic screen identifies LDHB as an essential gene for triple
      negative breast cancer.
AB  - Breast cancer has been redefined into three clinically relevant subclasses: (i)
      estrogen/progesterone receptor positive (ER+/PR+), (ii) HER2/ERRB2 positive, and
      (iii) those lacking expression of all three markers (triple negative or basal
      like). While targeted therapies for ER+/PR+ and HER2+ tumors have revolutionized
      patient treatment and increased lifespan, an urgent need exists for identifying
      novel targets for triple-negative breast cancers. Here, we used integrative
      genomic analysis to identify candidate oncogenes in triple-negative breast tumors
      and assess their function through loss of function screening. Using this
      approach, we identify lactate dehydrogenase B (LDHB), a component of glycolytic
      metabolism, as an essential gene in triple-negative breast cancer. Loss of LDHB
      abrogated cell proliferation in vitro and arrested tumor growth in fully formed
      tumors in vivo. We find that LDHB and other related glycolysis genes are
      specifically upregulated in basal-like/triple-negative breast cancers as compared
      with other subtypes, suggesting that these tumors are distinctly glycolytic.
      Consistent with this, triple-negative breast cancer cell lines were more
      dependent on glycolysis for growth than luminal cell lines. Finally, we find that
      patients with breast cancer and high LDHB expression in their tumors had a poor
      clinical outcome. While previous studies have focused on the ubiquitous role of
      LDHA in tumor metabolism and growth, our data reveal that LDHB is upregulated and
      required only in certain cancer genotypes. These findings suggest that targeting
      LDHB or other components of lactate metabolism would be of clinical benefit in
      triple-negative breast cancer.

PMID- 23139211
TI  - SMAD2, SMAD3 and SMAD4 mutations in colorectal cancer.
AB  - Activation of the canonical TGF-beta signaling pathway provides growth inhibitory
      signals in the normal intestinal epithelium. Colorectal cancers (CRCs) frequently
      harbor somatic mutations in the pathway members TGFBR2 and SMAD4, but to what
      extent mutations in SMAD2 or SMAD3 contribute to tumorigenesis is unclear. A
      cohort of 744 primary CRCs and 36 CRC cell lines were sequenced for SMAD4, SMAD2,
      and SMAD3 and analyzed for allelic loss by single-nucleotide polymorphism (SNP)
      microarray analysis. Mutation spectra were compared between the genes, the
      pathogenicity of mutations was assessed, and relationships with clinicopathologic
      features were examined. The prevalence of SMAD4, SMAD2, and SMAD3 mutations in
      sporadic CRCs was 8.6% (64 of 744), 3.4% (25 of 744), and 4.3% (32 of 744),
      respectively. A significant overrepresentation of two genetic hits was detected
      for SMAD4 and SMAD3, consistent with these genes acting as tumor suppressors.
      SMAD4 mutations were associated with mucinous histology. The mutation spectra of
      SMAD2 and SMAD3 were highly similar to that of SMAD4, both in mutation type and
      location within the encoded proteins. In silico analyses suggested the majority
      of the mutations were pathogenic, with most missense changes predicted to reduce
      protein stability or hinder SMAD complex formation. The latter altered interface
      residues or disrupted the phosphorylation-regulated Ser-Ser-X-Ser motifs within
      SMAD2 and SMAD3. Functional analyses of selected mutations showed reductions in
      SMAD3 transcriptional activity and SMAD2-SMAD4 complex formation. Joint biallelic
      hits in SMAD2 and SMAD3 were overrepresented and mutually exclusive to SMAD4
      mutation, underlining the critical roles of these three proteins within the TGF
      beta signaling pathway.

PMID- 23139212
TI  - RANKL expression, function, and therapeutic targeting in multiple myeloma and
      chronic lymphocytic leukemia.
AB  - Bone destruction is a prominent feature of multiple myeloma, but conflicting data
      exist on the expression and pathophysiologic involvement of the bone remodeling
      ligand RANKL in this disease and the potential therapeutic benefits of its
      targeted inhibition. Here, we show that RANKL is expressed by primary multiple
      myeloma and chronic lymphocytic leukemia (CLL) cells, whereas release of soluble
      RANKL was observed exclusively with multiple myeloma cells and was strongly
      influenced by posttranscriptional/posttranslational regulation. Signaling via
      RANKL into multiple myeloma and CLL cells induced release of cytokines involved
      in disease pathophysiology. Both the effects of RANKL on osteoclastogenesis and
      cytokine production by malignant cells could be blocked by disruption of RANK
      RANKL interaction with denosumab. As we aimed to combine neutralization of RANKL
      with induction of antibody-dependent cellular cytotoxicity of natural killer (NK)
      cells against RANKL-expressing malignant cells and as denosumab does not
      stimulate NK reactivity, we generated RANK-Fc fusion proteins with modified Fc
      moieties. The latter displayed similar capacity compared with denosumab to
      neutralize the effects of RANKL on osteoclastogenesis in vitro, but also potently
      stimulated NK cell reactivity against primary RANKL-expressing malignant B cells,
      which was dependent on their engineered affinity to CD16. Our findings introduce
      Fc-optimized RANK-Ig fusion proteins as attractive tools to neutralize the
      detrimental function of RANKL while at the same time potently stimulating NK cell
      antitumor immunity.

PMID- 23139213
TI  - Characterization of rearrangements involving the ALK gene reveals a novel
      truncated form associated with tumor aggressiveness in neuroblastoma.
AB  - Activating mutations of the ALK gene have been identified in sporadic and
      familial cases of neuroblastoma (NB), a cancer of the peripheral nervous system,
      and are thought to be the primary mechanism of oncogenic activation of this
      receptor in this pediatric neoplasm. To address the possibility that ALK
      activation may occur through genomic rearrangements as detected in other cancers,
      we first took advantage of high-resolution array-comparative genomic
      hybridization to search for ALK rearrangements in NB samples. Using complementary
      experiments by capture/paired-end sequencing and FISH experiments, various types
      of rearrangements were fully characterized, including partial gains or
      amplifications, in several NB cell lines and primary tumors. In the CLB-Bar cell
      line, we described a genomic rearrangement associated with an amplification of
      the ALK locus, leading to the expression of a 170 kDa protein lacking part of the
      extracellular domain encoded by exons 4 to 11, named ALK(Delta4-11). Analysis of
      genomic DNA from the tumor at diagnosis and relapse revealed that the ALK gene
      was amplified at diagnosis but that the rearranged ALK allele was observed at the
      relapse stage only, suggesting that it may be implicated in tumor aggressiveness.
      Consistently, oncogenic and tumorigenic properties of the ALK(Delta4-11) variant
      were shown after stable expression in NIH3T3 cells. Moreover, we documented an
      increased constitutive kinase activity of this variant, as well as an impaired
      maturation and retention into intracellular compartments. These results indicate
      that genomic rearrangements constitute an alternative mechanism to ALK point
      mutations resulting in receptor activation.

PMID- 23139214
TI  - Cell surface receptor FPR2 promotes antitumor host defense by limiting M2
      polarization of macrophages.
AB  - FPR2 (Fpr2 in mouse) is a G-protein-coupled receptor interacting with bacterial
      and host-derived chemotactic agonists. Fpr2 supports innate and adaptive immune
      responses as illustrated by the reduction in severity of allergic airway
      inflammation in Fpr2-KO mice, due to impaired trafficking of antigen-presenting
      dendritic cells (DC). The aim of this study is to examine the role of Fpr2 in
      host antitumor responses. We found that Fpr2-KO mice bearing subcutaneously
      implanted Lewis lung carcinoma (LLC) cells exhibited significantly shortened
      survival than normal mice due to more rapidly growing tumors. In contrast, in
      Fpr2-transgenic mice overexpressing Fpr2, subcutaneously implanted LLC tumors
      grew more slowly than those in wild-type (WT) littermates. Investigation of tumor
      tissues revealed an increased number of macrophages associated with tumors grown
      in Fpr2-KO mice. Macrophages derived from Fpr2-KO mice showed a more potent
      chemotactic response to LLC-derived supernatant (LLC Sup), which could be
      neutralized by an anti-CCL2 antibody. The increased chemotaxis of Fpr2-KO mouse
      macrophages in response to LLC Sup was due to their higher level expression of
      CCR4, a chemokine receptor that also recognizes the ligand CCL2. Furthermore,
      macrophages from Fpr2-KO mice acquired an M2 phenotype after stimulation with LLC
      Sup. These results suggest that Fpr2 plays an important role in host defense
      against implanted LLC by sustaining macrophages in an M1 phenotype with more
      potent antitumor activities.

PMID- 23139215
TI  - Probiotics prevent necrotizing enterocolitis by modulating enterocyte genes that
      regulate innate immune-mediated inflammation.
AB  - Necrotizing enterocolitis (NEC), an extensive intestinal inflammatory disease of
      premature infants, is caused, in part, by an excessive inflammatory response to
      initial bacterial colonization due to the immature expression of innate immune
      response genes. In a randomized placebo-controlled clinical trial,
      supplementation of very low birth weight infants with probiotics significantly
      reduced the incidence of NEC. The primary goal of this study was to determine
      whether secreted products of these two clinically effective probiotic strains,
      Bifidobacterium infantis and Lactobacillus acidophilus, prevented NEC by
      accelerating the maturation of intestinal innate immune response genes and
      whether both strains are required for this effect. After exposure to probiotic
      conditioned media (PCM), immature human enterocytes, immature human intestinal
      xenografts, and primary enterocyte cultures of NEC tissue (NEC-IEC) were assayed
      for an IL-8 and IL-6 response to inflammatory stimuli. The latter two models were
      also assayed for innate immune response gene expression. In the immature
      xenograft, PCM exposure significantly attenuated LPS and IL-1beta-induced IL-8
      and IL-6 expression, decreased TLR2 mRNA and TLR4 mRNA, and increased mRNA levels
      of specific negative regulators of inflammation, SIGIRR and Tollip. In NEC-IEC,
      PCM decreased TLR2-dependent IL-8 and IL-6 induction and increased SIGIRR and
      Tollip expression. The attenuated inflammatory response with PCM was reversed
      with Tollip siRNA-mediated knockdown. The anti-inflammatory secreted factor is a
      5- to 10-kDa molecule resistant to DNase, RNase, protease, heat stress, and acid
      exposure. B. infantis-conditioned media showed superior anti-inflammatory
      properties to that of L. acidophilus in immature human enterocytes, suggesting a
      strain specificity to this effect. We conclude that PCM promotes maturation of
      innate immune response gene expression, potentially explaining the protective
      effects of probiotics in clinical NEC.

PMID- 23139216
TI  - Psychoactive bacteria Lactobacillus rhamnosus (JB-1) elicits rapid frequency
      facilitation in vagal afferents.
AB  - Mounting evidence supports the influence of the gut microbiome on the local
      enteric nervous system and its effects on brain chemistry and relevant behavior.
      Vagal afferents are involved in some of these effects. We previously showed that
      ingestion of the probiotic bacterium Lactobacillus rhamnosus (JB-1) caused
      extensive neurochemical changes in the brain and behavior that were abrogated by
      prior vagotomy. Because information can be transmitted to the brain via primary
      afferents encoded as neuronal spike trains, our goal was to record those induced
      by JB-1 in vagal afferents in the mesenteric nerve bundle and thus determine the
      nature of the signals sent to the brain. Male Swiss Webster mice jejunal segments
      were cannulated ex vivo, and serosal and luminal compartments were perfused
      separately. Bacteria were added intraluminally. We found no evidence for
      translocation of labeled bacteria across the epithelium during the experiment. We
      recorded extracellular multi- and single-unit neuronal activity with glass
      suction pipettes. Within minutes of application, JB-1 increased the constitutive
      single- and multiunit firing rate of the mesenteric nerve bundle, but
      Lactobacillus salivarius (a negative control) or media alone were ineffective. JB
      1 significantly augmented multiunit discharge responses to an intraluminal
      distension pressure of 31 hPa. Prior subdiaphragmatic vagotomy abolished all of
      the JB-1-evoked effects. This detailed exploration of the neuronal spike firing
      that encodes behavioral signaling to the brain may be useful to identify
      effective psychoactive bacteria and thereby offer an alternative new perspective
      in the field of psychiatry and comorbid conditions.

PMID- 23139217
TI  - Hepatic overexpression of Abcb11 in mice promotes the conservation of bile acids
      within the enterohepatic circulation.
AB  - The bile salt export pump, encoded by ABCB11, is the predominant canalicular
      transport protein for biliary bile acid secretion. The level of ABCB11 expression
      in humans is widely variable yet the impact of this variability on human disease
      is not well defined. We aim to determine the effect of hepatic Abcb11
      overexpression on the enterohepatic circulation (EHC) in mice. We used a stable
      isotope dilution technique in transgenic mice overexpressing hepatic Abcb11 (TTR
      Abcb11) to determine the pool size, fractional turnover rate (FTR), and synthesis
      rate of the primary bile acid, cholic acid (CA). The gallbladder was cannulated
      to determine bile flow, bile acid composition, and the biliary secretion rates of
      CA, total bile acids, phospholipid, and cholesterol. The combined data allowed
      for estimation of the CA cycling time and the fraction of CA lost per cycle.
      Hepatic and intestinal gene and protein expression were determined by qPCR and
      Western blot. Abcb11 overexpression strongly decreased FTR and synthesis rate of
      CA. Abcb11 overexpression decreased the fraction of CA that was lost per cycle of
      the EHC. Hepatic expression of Cyp7a1 was suppressed by nearly 50% and ileal
      expression of FGF15 was increased more than eightfold in TTR-Abcb11 mice. Despite
      the increased intestinal reabsorption of bile acids, ileal Asbt expression was
      suppressed. Hepatic Abcb11 overexpression in mice increases the conservation of
      bile acids within the enterohepatic circulation. These data provide strong
      evidence for the existence of feed-forward communication between hepatic
      expression of a bile acid transport protein and the intestine.

PMID- 23139218
TI  - Heterogeneous nuclear ribonucleoprotein A2/B1 is a tissue-specific aldosterone
      target gene with prominent induction in the rat distal colon.
AB  - The steroid hormone aldosterone enhances transepithelial Na(+) reabsorption in
      tight epithelia and is crucial to achieve extracellular volume homeostasis and
      control of blood pressure. One of the main transport pathways regulated by
      aldosterone involves the epithelial Na(+) channel (ENaC), which constitutes the
      rate-limiting step of Na(+) reabsorption in parts of the distal nephron and the
      collecting duct, the distal colon, and sweat and salivary glands. Although these
      epithelial tissues share the same receptor for aldosterone (mineralocorticoid
      receptor, MR), and the same transport system (ENaC), it has become clear that the
      molecular mechanisms involved in the modulation of channel activity are tissue
      specific. Recent evidence suggests that aldosterone controls transcription and
      also translation of ENaC subunits in some cell types. A possible pathway for
      translational regulation is binding of regulatory proteins to ENaC subunit mRNAs,
      such as the heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1). In this
      study, we examined whether hnRNP A2/B1 is an aldosterone-target gene in vivo. Our
      data show that physiological levels of aldosterone markedly induce hnRNP A2/B1
      expression in an early and sustained manner in the late distal colon epithelium
      but not in other aldosterone-target tissues. The effect depends on MR but not on
      glucocorticoid receptor activity. We also demonstrate that the genomic region
      upstream of hnRNP A2/B1 contains aldosterone-responsive elements involved in the
      control of gene expression. We hypothesize that hnRNP A2/B1 is involved in the
      tissue-specific regulation of ENaC biosynthesis and may coordinate the response
      of other genes relevant for transepithelial Na(+) reabsorption by aldosterone.

PMID- 23139219
TI  - Capsaicin induces NKCC1 internalization and inhibits chloride secretion in
      colonic epithelial cells independently of TRPV1.
AB  - Colonic chloride secretion is regulated via the neurohormonal and immune systems.
      Exogenous chemicals (e.g., butyrate, propionate) can affect chloride secretion.
      Capsaicin, the pungent ingredient of the chili peppers, exerts various effects on
      gastrointestinal function. Capsaicin is known to activate the transient receptor
      potential vanilloid type 1 (TRPV1), expressed in the mesenteric nervous system.
      Recent studies have also demonstrated its presence in epithelial cells but its
      role remains uncertain. Because capsaicin has been reported to inhibit colonic
      chloride secretion, we tested whether this effect of capsaicin could occur by
      direct action on epithelial cells. In mouse colon and model T84 human colonic
      epithelial cells, we found that capsaicin inhibited forskolin-dependent short
      circuit current (FSK-I(sc)). Using PCR and Western blot, we demonstrated the
      presence of TRPV1 in colonic epithelial cells. In T84 cells, TRPV1 localized at
      the basolateral membrane and in vesicular compartments. In permeabilized
      monolayers, capsaicin activated apical chloride conductance, had no effect on
      basolateral potassium conductance, but induced NKCC1 internalization demonstrated
      by immunocytochemistry and basolateral surface biotinylation. AMG-9810, a potent
      inhibitor of TRPV1, did not prevent the inhibition of the FSK-I(sc) by capsaicin.
      Neither resiniferatoxin nor N-oleoyldopamine, two selective agonists of TRPV1,
      blocked the FSK-I(sc). Conversely capsaicin, resiniferatoxin, and N
      oleoyldopamine raised intracellular calcium ([Ca(2+)](i)) in T84 cells and AMG
      9810 blocked the rise in [Ca(2+)](i) induced by capsaicin and resiniferatoxin
      suggesting the presence of a functional TRPV1 channel. We conclude that capsaicin
      inhibits chloride secretion in part by causing NKCC1 internalization, but by a
      mechanism that appears to be independent of TRPV1.

PMID- 23139220
TI  - Neonatal maternal deprivation sensitizes voltage-gated sodium channel currents in
      colon-specific dorsal root ganglion neurons in rats.
AB  - Irritable bowel syndrome (IBS) is a common gastrointestinal disorder
      characterized by abdominal pain in association with altered bowel movements. The
      underlying mechanisms of visceral hypersensitivity remain elusive. This study was
      designed to examine the role for sodium channels in a rat model of chronic
      visceral hyperalgesia induced by neonatal maternal deprivation (NMD). Abdominal
      withdrawal reflex (AWR) scores were performed on adult male rats. Colon-specific
      dorsal root ganglion (DRG) neurons were labeled with DiI and acutely dissociated
      for measuring excitability and sodium channel current under whole-cell patch
      clamp configurations. The expression of Na(V)1.8 was analyzed by Western blot and
      quantitative real-time PCR. NMD significantly increased AWR scores, which lasted
      for ~6 wk in an association with hyperexcitability of colon DRG neurons. TTX
      resistant but not TTX-sensitive sodium current density was greatly enhanced in
      colon DRG neurons in NMD rats. Compared with controls, activation curves showed a
      leftward shift in NMD rats whereas inactivation curves did not differ
      significantly. NMD markedly accelerated the activation time of peak current
      amplitude without any changes in inactivation time. Furthermore, NMD remarkably
      enhanced expression of Na(V)1.8 at protein levels but not at mRNA levels in colon
      related DRGs. The expression of Na(V)1.9 was not altered after NMD. These data
      suggest that NMD enhances TTX-resistant sodium activity of colon DRG neurons,
      which is most likely mediated by a leftward shift of activation curve and by
      enhanced expression of Na(V)1.8 at protein levels, thus identifying a specific
      molecular mechanism underlying chronic visceral pain and sensitization in
      patients with IBS.

PMID- 23139221
TI  - Ethanol administration exacerbates the abnormalities in hepatic lipid oxidation
      in genetically obese mice.
AB  - Alcohol consumption synergistically increases the risk and severity of liver
      damage in obese patients. To gain insight into cellular or molecular mechanisms
      underlying the development of fatty liver caused by ethanol-obesity synergism, we
      have carried out animal experiments that examine the effects of ethanol
      administration in genetically obese mice. Lean wild-type (WT) and obese (ob/ob)
      mice were subjected to ethanol feeding for 4 wk using a modified Lieber-DeCarli
      diet. After ethanol feeding, the ob/ob mice displayed much more pronounced
      changes in terms of liver steatosis and elevated plasma levels of alanine
      aminotransferase and aspartate aminotransferase, indicators of liver injury,
      compared with control mice. Mechanistic studies showed that ethanol feeding
      augmented the impairment of hepatic sirtuin 1 (SIRT1)-AMP-activated kinase (AMPK)
      signaling in the ob/ob mice. Moreover, the impairment of SIRT1-AMPK signaling was
      closely associated with altered hepatic functional activity of peroxisome
      proliferator-activated receptor gamma coactivator-alpha and lipin-1, two vital
      downstream lipid regulators, which ultimately contributed to aggravated fatty
      liver observed in ethanol-fed ob/ob mice. Taken together, our novel findings
      suggest that ethanol administration to obese mice exacerbates fatty liver via
      impairment of the hepatic lipid metabolism pathways mediated largely by a central
      signaling system, the SIRT1-AMPK axis.

PMID- 23139223
TI  - D-Glucose modulates intestinal Niemann-Pick C1-like 1 (NPC1L1) gene expression
      via transcriptional regulation.
AB  - The expression of intestinal Niemann-Pick C1-like 1 (NPC1L1) cholesterol
      transporter has been shown to be elevated in patients with diseases associated
      with hypercholesterolemia such as diabetes mellitus. High levels of glucose were
      shown to directly increase the expression of NPC1L1 in intestinal epithelial
      cells, but the underlying mechanisms are not fully defined. The present studies
      were, therefore, undertaken to examine the transcriptional regulation of NPC1L1
      expression in human intestinal Caco2 cells in response to glucose. Removal of
      glucose from the culture medium of Caco2 cells for 24 h significantly decreased
      the NPC1L1 mRNA, protein expression, as well as the promoter activity. Glucose
      replenishment significantly increased the promoter activity of NPC1L1 in a dose
      dependent manner compared with control cells. Exposure of Caco2 cells to
      nonmetabolizable form of glucose, 3-O-methyl-d-glucopyranose (OMG) had no effect
      on NPC1L1 promoter activity, indicating that the observed effects are dependent
      on glucose metabolism. Furthermore, glucose-mediated increase in promoter
      activity was abrogated in the presence of okadaic acid, suggesting the
      involvement of protein phosphatases. Glucose effects on several deletion
      constructs of NPC1L1 promoter demonstrated that cis elements mediating the
      effects of glucose are located in the region between -291 and +56 of NPC1L1
      promoter. Consistent with the effects of glucose removal on NPC1L1 expression in
      Caco2 cells, 24-h fasting resulted in a significant decrease in the relative
      expression of NPC1L1 in mouse jejunum. In conclusion, glucose appears to directly
      modulate NPC1L1 expression via transcriptional mechanisms and the involvement of
      phosphatase-dependent pathways.

PMID- 23139222
TI  - Modulation of the gut microbiota with antibiotic treatment suppresses whole body
      urea production in neonatal pigs.
AB  - We examined whether changes in the gut microbiota induced by clinically relevant
      interventions would impact the bioavailability of dietary amino acids in
      neonates. We tested the hypothesis that modulation of the gut microbiota in
      neonatal pigs receiving no treatment (control), intravenously administered
      antibiotics, or probiotics affects whole body nitrogen and amino acid turnover.
      We quantified whole body urea kinetics, threonine fluxes, and threonine disposal
      into protein, oxidation, and tissue protein synthesis with stable isotope
      techniques. Compared with controls, antibiotics reduced the number and diversity
      of bacterial species in the distal small intestine (SI) and colon. Antibiotics
      decreased plasma urea concentrations via decreased urea synthesis. Antibiotics
      elevated threonine plasma concentrations and turnover, as well as whole body
      protein synthesis and proteolysis. Antibiotics decreased protein synthesis rate
      in the proximal SI and liver but did not affect the distal SI, colon, or muscle.
      Probiotics induced a bifidogenic microbiota and decreased plasma urea
      concentrations but did not affect whole body threonine or protein metabolism.
      Probiotics decreased protein synthesis in the proximal SI but not in other
      tissues. In conclusion, modulation of the gut microbiota by antibiotics and
      probiotics reduced hepatic ureagenesis and intestinal protein synthesis, but
      neither altered whole body net threonine balance. These findings suggest that
      changes in amino acid and nitrogen metabolism resulting from antibiotic- or
      probiotic-induced shifts in the microbiota are localized to the gut and liver and
      have limited impact on whole body growth and anabolism in neonatal piglets.

PMID- 23139224
TI  - Activation of cannabinoid receptor 2 reduces inflammation in acute experimental
      pancreatitis via intra-acinar activation of p38 and MK2-dependent mechanisms.
AB  - The endocannabinoid system has been shown to mediate beneficial effects on
      gastrointestinal inflammation via cannabinoid receptors 1 (CB(1)) and 2 (CB(2)).
      These receptors have also been reported to activate the MAP kinases p38 and c-Jun
      NH(2)-terminal kinase (JNK), which are involved in early acinar events leading to
      acute pancreatitis and induction of proinflammatory cytokines. Our aim was to
      examine the role of cannabinoid receptor activation in an experimental model of
      acute pancreatitis and the potential involvement of MAP kinases. Cerulein
      pancreatitis was induced in wild-type, CB(1)-/-, and MK2-/- mice pretreated with
      selective cannabinoid receptor agonists or antagonists. Severity of pancreatitis
      was determined by serum amylase and IL-6 levels, intracellular activation of
      pancreatic trypsinogen, lung myeloperoxidase activity, pancreatic edema, and
      histological examinations. Pancreatic lysates were investigated by Western
      blotting using phospho-specific antibodies against p38 and JNK. Quantitative PCR
      data, Western blotting experiments, and immunohistochemistry clearly show that
      CB(1) and CB(2) are expressed in mouse pancreatic acini. During acute
      pancreatitis, an upregulation especially of CB(2) on apoptotic cells occurred.
      The unselective CB(1)/CB(2) agonist HU210 ameliorated pancreatitis in wild-type
      and CB(1)-/- mice, indicating that this effect is mediated by CB(2). Furthermore,
      blockade of CB(2), not CB(1), with selective antagonists engraved pathology.
      Stimulation with a selective CB(2) agonist attenuated acute pancreatitis and an
      increased activation of p38 was observed in the acini. With use of MK2-/- mice,
      it could be demonstrated that this attenuation is dependent on MK2. Hence, using
      the MK2-/- mouse model we reveal a novel CB(2)-activated and MAP kinase-dependent
      pathway that modulates cytokine expression and reduces pancreatic injury and
      affiliated complications.

PMID- 23139225
TI  - Optimal projection for transcatheter aortic valve implantation determined from
      the reference projection angles.
AB  - INTRODUCTION: An optimal fluoroscopic working view projection (OP) with all three
      aortic sinuses aligned is crucial during trans-catheter aortic valve implantation
      (TAVI). The aim of this study was to identify simple reference projection angles,
      which would act as a starting point for the operator to help determine OP for
      patients undergoing TAVI. METHODS: During the period under consideration, 50
      patients underwent TAVI. Procedural data and outcomes were collected
      prospectively on a dedicated database. Optimal angiographic deployment angles
      were achieved for all patients by starting in an anteroposterior caudal 15
      degrees projection and then adjusting according to the initial image, with
      multiple small volume contrast injections undertaken to determine when all three
      aortic cusps were aligned (OP). RESULTS: OP angles for the 50 cases were plotted
      on a graph. After normality testing confirmed that all angles were normally
      distributed, regression analysis enabled a regression line to be calculated. The
      equation for the regression line was defined as cranial/caudal intercept -16.4 +/
      1.5 (SE of the coefficient), P < 0.0001, slope of regression line LAO/RAO + 0.53
      +/- 0.1 (SE of the coefficient SE), P < 0.0001). CONCLUSIONS: As the regression
      line and its equation represents an acceptable estimate of the true relationship
      between Cranial/Caudal and LAO/RAO, to determine OP while remaining close to the
      regression line we suggest starting in LAO = 8.9, Caudal = -11.4 (which represent
      the mean values of these two variables), and then increasing the caudal angle by
      approximately 0.5 degrees for every increase of 1 degree of the LAO angle or
      decreasing the caudal angle by 0.53 degrees for every decrease of 1 degree in LAO
      until all three aortic sinuses are in line which represents OP.

PMID- 23139226
TI  - Can knee arthroplasty play a role in weight management in knee osteoarthritis?

PMID- 23139227
TI  - Electronic and atomic structure of Ba8Ga16Ge(30-x)Si(x) type I clathrates: Ge and
      Ga XAFS study.
AB  - X-ray absorption fine structure spectroscopy at the Ga and Ge K-edges was used to
      study changes in the Ga and Ge electronic structure and local coordination
      geometry as a function of composition in Ba(8)Ga(16)Ge(30-x)Si(x) type I
      clathrates (x = 0, 7.5, 9.1, 10.7, 13.4 and 30). Based on XANES data, the partial
      density of unoccupied states with p character is modified for both Ga and Ge upon
      Si substitution. Among the specimens which contain both Ge and Si, we found that
      the specimen with the highest measured power factor (i.e., x = 7.5) has the
      lowest density of unoccupied states for both Ga and Ge. Our experimental results
      are qualitatively consistent with computational results based on density
      functional theory, indicating that a series of pertinent electronic states are
      modified by Si p states. This suggests that an increase in the electron density
      near the Fermi level for an optimal Si substitution leads to an increase in the
      Seebeck coefficient and consequently in the power factor, according to the Cutler
      Mott relation. Based on quantitative analysis of EXAFS spectra, we found that Ga
      has more Si neighbors than Ge, indicating that Si resides preferentially next to
      Ga. Both the Ge-Ga/Ge and Ga-Ge/Ga coordination distances remain relatively
      unchanged (~2.51 A) regardless of the degree of Si substitution. Furthermore, the
      Ge-Si and Ga-Si coordination distances remain relatively unchanged at ~2.41 and
      ~2.45 A, respectively, regardless of the degree of Si substitution. For the
      Ba(8)Ga(16)Si(30) specimen, on average, Ga is coordinated with 0.9 Ga and 3.1 Si
      at roughly the same distance of ~2.50 A. The number of Ga-Ga bonds is consistent
      with the fact that Ga is distributed on the framework sites in a way which
      reduces the number of Ga-Ga bonds relative to that based on a random
      distribution. An understanding of the underlying physics of the structure
      property relationship provides for potential additional routes for tuning the
      electronic properties of clathrates for thermoelectric applications.

PMID- 23139228
TI  - Design, synthesis and structure-activity relationship of novel insecticidal
      dichloro-allyloxy-phenol derivatives containing substituted pyrazol-3-ols.
AB  - BACKGROUND: Pyridalyl, consisting of dicholoro-allyoxy-phenol moiety, is a novel
      class of insecticide showing extraordinary activities against various
      lepidopterous and thysanopterous pests on cotton and vegetables. To discover
      further novel insecticides, a series of new dichloro-allyloxy-phenol derivatives
      containing substituted pyrazol-3-ol moieties were designed and synthesised via
      the intermediate derivatisation method. RESULTS: The target compounds were
      characterised by (1) H NMR, IR, MS and elemental analysis. Bioassays indicated
      that some of these compounds exhibited good insecticidal activities against
      diamondback moth (Plutella xylostella) at 6.25 mg L(-1) . The structure-activity
      relationship is discussed. CONCLUSION: The present work demonstrates that
      dichloro-allyloxy-phenol derivatives with substituted phenylpyrazole moieties can
      be used as lead compounds to develop further novel insecticides.

PMID- 23139229
TI  - Increased risk of arthropathies and joint replacement surgery in patients with
      genetic hemochromatosis: a study of 3,531 patients and their 11,794 first-degree
      relatives.
AB  - OBJECTIVE: Genetic hemochromatosis (GH) is an autosomal recessive disease in
      individuals of Northern and Western European descent. Heterozygosity for the
      C282Y mutation is common (6-20%). Arthropathy is one of the few complications of
      GH suggested not to be associated with iron body stores; synovial iron deposition
      remains in iron-depleted patients. Previous studies suggest an elevated
      prevalence of clinical and radiographic signs of arthropathy in patients with GH,
      and 2 smaller studies suggest a possibly elevated risk of joint replacement
      surgery, but more mixed results are shown regarding risks with HFE genotype. We
      therefore assessed the risks of arthropathy and joint replacement surgery in
      patients with GH and in their first-degree relatives (FDRs). METHODS: We
      performed a population-based cohort study of 3,531 patients with GH and of their
      11,794 FDRs (assumed to be heterozygous for the C282Y mutation) using nationwide
      Swedish population-based health and census registers. Hazard ratios (HRs) of
      arthropathies and joint replacement surgeries among patients and their FDRs
      (versus the general population) were assessed using Cox regression. RESULTS:
      Between 1997 and 2005, 406 of 3,531 patients were reported/hospitalized with any
      noninfectious arthropathies, including osteoarthritis, corresponding to an HR of
      2.38 (95% confidence interval [95% CI] 2.14-2.64). Patients were also at
      increased risk of hip replacement (HR 2.77, 95% CI 2.27-3.38) and knee
      replacement (HR 2.14, 95% CI 1.58-2.88) surgery. Among the 11,794 FDRs (patients
      excluded), we found no increased risk of any of the joint morbidities.
      CONCLUSION: Patients with GH, but not their FDRs, are at increased risk of
      arthropathies, including the need for joint replacement surgery.

PMID- 23139230
TI  - The role of temperature in the magnetic irreversibility of type-I Pb
      superconductors.
AB  - Evidence  of how temperature plays a role in the magnetic irreversibility in the
      intermediate state of a cylinder and various disks of pure type-I superconducting
      lead is presented. Isothermal measurements of first magnetization curves and
      hysteresis cycles are analyzed in a reduced representation that defines an
      equilibrium state for flux penetration in all the samples and reveals that flux
      expulsion depends on temperature in the disks but not in the cylinder. The
      magnetic field at which irreversibility sets in along the descending branch of
      the cycle and the remnant magnetization at zero field are found to decrease with
      temperature. The contributions to irreversibility of the geometrical barrier and
      the energy minima associated with stress defects that act as pinning centers on
      normal-superconductor interfaces are discussed in an effort to account for the
      results obtained.

PMID- 23139231
TI  - Electrospun synthetic and natural nanofibers for regenerative medicine and stem
      cells.
AB  - Nanofibers are attractive substrates for tissue regeneration applications because
      they structurally mimic the native extracellular matrix. Electrospinning has been
      recognized as one of the most efficient techniques to fabricate polymer
      nanofibers. Recent research has demonstrated that cellular responses, for example
      attachment, proliferation and differentiation, can be modulated by tuning
      nanofiber properties. In combination with other processing techniques, such as
      particulate leaching or three-dimensional printing, nanofibrous scaffolds
      incorporating macroporous networks could be developed to enhance infiltration of
      cells. Three dimensional nanofiber-based constructs offer an opportunity to
      achieve advanced functional tissue regeneration. This review explores the
      advantageous effects of nanofibers on cell behaviors compared to traditional
      scaffolds.

PMID- 23139232
TI  - Role of sterol 3-ketoreductase sensitivity in susceptibility to the fungicide
      fenhexamid in Botrytis cinerea and other phytopathogenic fungi.
AB  - BACKGROUND: The narrow-spectrum fungicide fenhexamid was introduced into French
      vineyards in 2000 to control grey mould caused by a complex of two cryptic
      species: Botrytis cinerea, the predominant species sensitive to fenhexamid, and
      Botrytis pseudocinerea, naturally resistant. Fenhexamid was suggested to inhibit
      the 3-ketoreductase involved at C-4 demethylation steps during ergosterol
      biosynthesis, as revealed by its effects on the B. cinerea sterol profile.
      Resistance monitoring studies have hitherto identified two B. cinerea fenhexamid
      resistant phenotypes, both resulting from mutations in the erg27 gene encoding 3
      ketoreductase. RESULTS: The role of 3-ketoreductase sensitivity in fungal
      susceptibility to fenhexamid was investigated by studying sterol profiles and
      microsomal 3-ketoreductase in various fungal strains. Fenhexamid does inhibit B.
      cinerea 3-ketoreductase activity. Erg27 mutations causing amino acid
      substitutions in or near the transmembrane domain strongly decrease the affinity
      of fenhexamid for 3-ketoreductase. Fenhexamid has very low affinities for 3
      ketoreductase in inherently resistant species, whether closely related to B.
      cinerea, like B. pseudocinerea, or more distantly related, like Nectria
      haematococca. CONCLUSION: erg27 mutation and erg27 polymorphism may therefore
      contribute to the unfavourable binding of fenhexamid to its target, 3
      ketoreductase, explaining the acquisition of fenhexamid resistance in B. cinerea
      and the narrow spectrum of this fungicide.

PMID- 23139233
TI  - Risk of non-Hodgkin's lymphoma in primary Sjogren's syndrome: a population-based
      study.
AB  - OBJECTIVE: Primary Sjogren's syndrome (SS) is associated with an increased risk
      of non-Hodgkin's lymphoma (NHL), but the reported prevalence and risk vary
      considerably. The objective of this study was to determine the risk of NHL in a
      well-defined population-based primary SS cohort in Norway. METHODS: The authors
      examined all patients fulfilling the American-European Consensus Group criteria
      for primary SS from 2 Norwegian counties and compared the data to the Cancer
      Registry of Norway to identify the primary SS patients who had lymphoma. In
      addition, lymphoma patient files from the same period were reviewed for
      undiagnosed primary SS to ensure the quality of registry data. RESULTS: As of
      July 1, 2009, 443 living subjects with primary SS were identified in an area with
      896,840 inhabitants, which is 18.6% of the total population of Norway. Seven
      cases of NHL (1.6%) were found during a total followup of 3,813 person-years,
      resulting in a standardized incidence ratio of 9.0 (95% confidence interval 7.1
      26.3) for NHL in primary SS patients. CONCLUSION: The risk of NHL in patients
      with primary SS in Norway is increased 9 times compared with the general
      population. This is in accordance with recent studies, and the quality and
      completeness of the registries and strict use of diagnostic criteria support the
      validity of the results.

PMID- 23139234
TI  - Stanley N. Cohen - an interview by Judy Peng.
AB  - Biotechnology Journal talks to Prof. Stanley Cohen after his plenary lecture at
      the International Biotechnology Symposium, Sept 2012, in Daegu, Korea.

PMID- 23139235
TI  - Fe charge state adjustment in ZnO upon ion implantation.
AB  - The influence of the ion implantation process on the charge state of dilute
      (57)Fe impurities implanted as radioactive (57)Mn in ZnO is investigated by
      (57)Fe emission Mossbauer spectroscopy. One sample is additionally implanted with
      stable (23)Na impurities. Both Fe(2+) and Fe(3+) charge states are observed, and
      the Fe(3+)/Fe(2+) ratio is found to increase with the fluence of both
      (57)Mn/(57)Fe and (23)Na ions, demonstrating that the build-up of Fe(3+) is not
      related to the chemical nature of the implanted ions. The results are interpreted
      in terms of radiation damage induced changes of the Fermi level, and illustrate
      that the Fe(3+)/Fe(2+) ratio can be adjusted by ion implantation. The spin
      lattice relaxation time for Fe(3+) in ZnO is found to be independent of the
      implantation fluence, and is evidently an intrinsic property of the system.

PMID- 23139236
TI  - Enhancing microscopy images of minerals through morphological center operator
      based feature extraction.
AB  - To well enhance the mineral image and image details obtained by microscopes, an
      effective mineral image enhancement algorithm through feature extraction using
      the morphological center operator is proposed in this work. First, mineral image
      feature extraction based on the morphological center operator is proposed and
      discussed. Second, the multiscale extension of the mineral image feature
      extraction is given by using the multiscale structuring elements. Third, the
      important mineral image features at multiscales of image are extracted and used
      to construct the final mineral features for mineral image enhancement. Finally,
      the original mineral image is well enhanced through importing the extracted final
      mineral image features into the original mineral image. Experimental results on
      different types of microscopy images of minerals verified the effective
      performance of the proposed algorithm for microscopy mineral image enhancement.

PMID- 23139237
TI  - Sensitivity of the entomopathogenic fungus Beauveria bassiana (Bals.-Criv.)
      Vuill. to selected herbicides.
AB  - BACKGROUND: The in vitro effect of six commonly used herbicides viz.,
      amidosulfuron, dicamba, metribuzin, pyridate, S-metolachlor and tembotrione on
      mycelial growth of entomopathogenic fungus Beauveriabassiana (ATCC 74040) was
      investigated. Mycelial growthrates at 15 and 25 degrees C were evaluated on PDA
      plates containing 100, 75, 50, 25, 12.5, 6.25 and 0% of the recommended
      application rate of each selected herbicide. The tested herbicides were
      classified in 4 scoring categories based on reduction of mycelial growth in
      toxicity tests. RESULTS: All six herbicides had a fungistatic effect of varying
      intensities, dependent on their rate in medium, on B. bassiana. The present study
      showed that B. bassiana is sensitive to all tested herbicides, particularly at
      recommended as well as lower field rates. Metribuzin, S-metolachlor and
      tembotrione had a strong fungistatic effect on mycelial growth even at rates 25
      and 12.5%.Pyridate was slightly harmful, depending on the rate and temperature.
      Dicamba and amidosulfuron had slight effect on mycelial growth. Sporulation and
      conidial germination of B. bassiana were significantly inhibited by all tested
      herbicides. Amidosulfuron and dicamba, both at 100% rate, had the lowest
      inhibitory effect on sporulation, i.e. 24% and 44%, respectively. Other
      herbicides in test showed much higher inhibitory effect on sporulation (69-95%).
      With exception of dicamba with 33% of conidial germination inhibition all other
      herbicides in test inhibited conidial germination for 70-100%. At 200% dosage,
      inhibition rates even increased. CONCLUSION: Of all tested herbicides,
      amidosulfuron and dicamba showed the least adverse effects and are therefore
      probably compatible with B. bassiana in the field.

PMID- 23139238
TI  - In utero azathioprine exposure and increased utilization of special educational
      services in children born to mothers with systemic lupus erythematosus.
AB  - OBJECTIVE: Azathioprine (AZA) is recognized among immunosuppressive medications
      as relatively safe during pregnancy for women with systemic lupus erythematosus
      (SLE) requiring aggressive treatment. This pilot study aimed to determine whether
      SLE therapy during pregnancy was associated with developmental delays in
      offspring. METHODS: This cohort study included SLE patients with at least one
      live birth postdiagnosis. Medical histories were obtained via interviews and
      chart review. Multiple logistic regression was used to examine associations
      between SLE therapy during pregnancy and maternal report of special educational
      (SE) requirements (as proxy for developmental delays) among offspring. Propensity
      scoring (incorporating corticosteroid use, lupus flare, and lupus nephritis) was
      used to account for disease severity. RESULTS: Of 60 eligible offspring from 38
      mothers, 15 required SE services, the most common indication for which was speech
      delay. Seven (54%) of the 13 children with in utero AZA exposure utilized SE
      services versus 8 (17%) of 47 nonexposed children (P < 0.01). After adjustment
      for pregnancy duration, small for gestational age, propensity score, maternal
      education level, and antiphospholipid antibody syndrome, AZA was significantly
      associated with SE utilization occurring from age 2 years onward (odds ratio 6.6,
      95% confidence interval 1.0-43.3), and bordered on significance for utilization
      at any age or age <2 years. CONCLUSION: AZA exposure during SLE pregnancy was
      independently associated with increased SE utilization in offspring, after
      controlling for confounders. Further research is indicated to fully characterize
      developmental outcomes among offspring with in utero AZA exposure. Vigilance and
      early interventions for suspected developmental delays among exposed offspring
      may be warranted.

PMID- 23139239
TI  - Directed modulation of protein kinase C isozyme selectivity with bisubstrate
      based inhibitors.
AB  - Kinases present an attractive target for drug development, since they are
      involved in vital cellular processes and are implicated in a variety of diseases,
      such as cancer and diabetes. However, obtaining selectivity for a specific kinase
      over others is difficult since many current kinase inhibitors exclusively target
      the highly conserved kinase ATP binding domain. Previously, a microarray-based
      strategy to discover so-called bisubstrate-based inhibitors that target the more
      specific peptide binding groove in addition to the ATP binding site was
      described. One attractive feature of this strategy is the opportunity to tune the
      selectivity of these inhibitors by systematically varying components. In an
      extension to this previous work, this study explores the potential of this guided
      selectivity modulation, leading to a series of inhibitors with different
      selectivity profiles against highly homologous protein kinase C (PKC) isozymes.
      Of the inhibitors studied, most exhibited improved potency and selectivity
      compared with their constituent parts. Furthermore, the selectivity was found to
      be tunable either through modification of the pseudosubstrate peptide (peptide
      binding groove) or the ATP-competitive part (ATP binding site). In a number of
      cases, the selectivity of the construct could be predicted from the initial
      peptide substrate profiling experiment. Since this strategy is applicable to all
      kinase sets, it could be used to rapidly develop uniquely selective inhibitors.

PMID- 23139240
TI  - Pulmonary hypertension and other potentially fatal pulmonary complications in
      systemic juvenile idiopathic arthritis.
AB  - OBJECTIVE: Systemic juvenile idiopathic arthritis (JIA) is characterized by
      fevers, rash, and arthritis, for which interleukin-1 (IL-1) and IL-6 inhibitors
      appear to be effective treatments. Pulmonary arterial hypertension (PAH),
      interstitial lung disease (ILD), and alveolar proteinosis (AP) have recently been
      reported with increased frequency in systemic JIA patients. Our aim was to
      characterize and compare systemic JIA patients with these complications to a
      larger cohort of systemic JIA patients. METHODS: Systemic JIA patients who
      developed PAH, ILD, and/or AP were identified through an electronic Listserv and
      their demographic, systemic JIA, and pulmonary disease characteristics as well as
      their medication exposure information were collected. Patients with these
      features were compared to a cohort of systemic JIA patients enrolled in the
      Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry. RESULTS:
      The patients (n = 25) were significantly (P < 0.05) more likely than the CARRA
      registry cohort (n = 389) to be female; have more systemic features; and have
      been exposed to an IL-1 inhibitor, tocilizumab, corticosteroids, intravenous
      immunoglobulin, cyclosporine, and cyclophosphamide. Twenty patients (80%) were
      diagnosed with pulmonary disease after 2004. Twenty patients (80%) had macrophage
      activation syndrome (MAS) during their disease course and 15 patients (60%) had
      MAS at pulmonary diagnosis. Sixteen patients had PAH, 5 had AP, and 7 had ILD.
      Seventeen patients (68%) were taking or recently discontinued (<1 month) a
      biologic agent at pulmonary symptom onset; 12 patients (48%) were taking anti-IL
      1 therapy (primarily anakinra). Seventeen patients (68%) died at a mean of 10.2
      months from the diagnosis of pulmonary complications. CONCLUSION: PAH, AP, and
      ILD are underrecognized complications of systemic JIA that are frequently fatal.
      These complications may be the result of severe uncontrolled systemic disease
      activity and may be influenced by medication exposure.

PMID- 23139241
TI  - Transcriptional and post-transcriptional regulation of cGMP-dependent protein
      kinase (PKG-I): pathophysiological significance.
AB  - The ability of the endothelium to produce nitric oxide, which induces generation
      of cyclic guanosine monophosphate (cGMP) that activates cGMP-dependent protein
      kinase (PKG-I), in vascular smooth muscle cells (VSMCs), is essential for the
      maintenance of vascular homeostasis. Yet, disturbance of this nitric
      oxide/cGMP/PKG-I pathway has been shown to play an important role in many
      cardiovascular diseases. In the last two decades, in vitro and in vivo models of
      vascular injury have shown that PKG-I is suppressed following nitric oxide, cGMP,
      cytokine, and growth factor stimulation. The molecular basis for these changes in
      PKG-I expression is still poorly understood, and they are likely to be mediated
      by a number of processes, including changes in gene transcription, mRNA
      stability, protein synthesis, or protein degradation. Emerging studies have begun
      to define mechanisms responsible for changes in PKG-I expression and have
      identified cis- and trans-acting regulatory elements, with a plausible role being
      attributed to post-translational control of PKG-I protein levels. This review
      will focus mainly on recent advances in understanding of the regulation of PKG-I
      expression in VSMCs, with an emphasis on the physiological and pathological
      significance of PKG-I down-regulation in VSMCs in certain circumstances.

PMID- 23139243
TI  - Expanded CTG repeats trigger miRNA alterations in Drosophila that are conserved
      in myotonic dystrophy type 1 patients.
AB  - Myotonic dystrophy type 1 (DM1) is caused by the expansion of CTG repeats in the
      3' untranslated region of the DMPK gene. Several missplicing events and
      transcriptional alterations have been described in DM1 patients. A large number
      of these defects have been reproduced in animal models expressing CTG repeats
      alone. Recent studies have also reported miRNA dysregulation in DM1 patients. In
      this work, a Drosophila model was used to investigate miRNA transcriptome
      alterations in the muscle, specifically triggered by CTG expansions. Twenty
      miRNAs were differentially expressed in CTG-expressing flies. Of these, 19 were
      down-regulated, whereas 1 was up-regulated. This trend was confirmed for those
      miRNAs conserved between Drosophila and humans (miR-1, miR-7 and miR-10) in
      muscle biopsies from DM1 patients. Consistently, at least seven target
      transcripts of these miRNAs were up-regulated in DM1 skeletal muscles. The
      mechanisms involved in dysregulation of miR-7 included a reduction of its primary
      precursor both in CTG-expressing flies and in DM1 patients. Additionally, a
      regulatory role for Muscleblind (Mbl) was also suggested for miR-1 and miR-7, as
      these miRNAs were down-regulated in flies where Mbl had been silenced. Finally,
      the physiological relevance of miRNA dysregulation was demonstrated for miR-10,
      since over-expression of this miRNA in Drosophila extended the lifespan of CTG
      expressing flies. Taken together, our results contribute to our understanding of
      the origin and the role of miRNA alterations in DM1.

PMID- 23139244
TI  - Assessment of cartilage changes over time in knee osteoarthritis disease
      modifying osteoarthritis drug trials using semiquantitative and quantitative
      methods: pros and cons.
AB  - OBJECTIVE: To evaluate the impact of 2 magnetic resonance imaging (MRI) sequences
      on cartilage defect assessment in knee osteoarthritis (OA) patients and the
      sensitivity to change over time comparing cartilage defect (semiquantitative)
      with cartilage volume loss (quantitative) methods. METHODS: Gradient-echo (GRE)
      and intermediate-weighted fast spin-echo (IW-FSE) sequences were compared. Knee
      OA MRIs were from two 2-year studies (cohort 1, n = 55; cohort 2, n = 143). For
      both cohorts, a GRE sequence was used and patients in cohort 1 underwent an
      additional IW-FSE sequence. Cohort 2 included patients from a previous trial.
      Cartilage defects and cartilage volume were evaluated. RESULTS: The cartilage
      defect assessment provided consistently significantly higher scores in IW-FSE
      than in GRE sequences at baseline and 2 years. However, there was no difference
      in the change at 2 years between the sequences. The standardized response mean
      (SRM) for change did not show a difference between the 2 sequences, but was
      consistently higher (2-2.5-fold) for the quantitative method. The cartilage
      defect score change between the 2 treatment groups revealed a trend toward
      significance only in the medial tibial plateau, whereas the change in cartilage
      volume loss demonstrated a significant difference in the global knee, global
      femur, lateral femur, and lateral compartment. The SRMs for the treatment groups
      combined were markedly higher for cartilage volume loss than for the defect
      scoring by 4.3- to 6.0-fold. CONCLUSION: The direct comparison between GRE and IW
      FSE sequences did not suggest superior sensitivity to cartilage defect change
      over time of one sequence over the other. Interestingly, the quantitative
      cartilage volume assessment was more sensitive than the semiquantitative scoring
      in the detection of treatment effect on OA cartilage changes.

PMID- 23139242
TI  - iPS cell modeling of Best disease: insights into the pathophysiology of an
      inherited macular degeneration.
AB  - Best disease (BD) is an inherited degenerative disease of the human macula that
      results in progressive and irreversible central vision loss. It is caused by
      mutations in the retinal pigment epithelium (RPE) gene BESTROPHIN1 (BEST1),
      which, through mechanism(s) that remain unclear, lead to the accumulation of
      subretinal fluid and autofluorescent waste products from shed photoreceptor outer
      segments (POSs). We employed human iPS cell (hiPSC) technology to generate RPE
      from BD patients and unaffected siblings in order to examine the cellular and
      molecular processes underlying this disease. Consistent with the clinical
      phenotype of BD, RPE from mutant hiPSCs displayed disrupted fluid flux and
      increased accrual of autofluorescent material after long-term POS feeding when
      compared with hiPSC-RPE from unaffected siblings. On a molecular level, RHODOPSIN
      degradation after POS feeding was delayed in BD hiPSC-RPE relative to unaffected
      sibling hiPSC-RPE, directly implicating impaired POS handling in the
      pathophysiology of the disease. In addition, stimulated calcium responses
      differed between BD and normal sibling hiPSC-RPE, as did oxidative stress levels
      after chronic POS feeding. Subcellular localization, fractionation and co
      immunoprecipitation experiments in hiPSC-RPE and human prenatal RPE further
      linked BEST1 to the regulation and release of endoplasmic reticulum calcium
      stores. Since calcium signaling and oxidative stress are critical regulators of
      fluid flow and protein degradation, these findings likely contribute to the
      clinical picture of BD. In a larger context, this report demonstrates the
      potential to use patient-specific hiPSCs to model and study maculopathies, an
      important class of blinding disorders in humans.

PMID- 23139245
TI  - LC-MS-MS determination and pharmacokinetic study of the novel anti-tumor
      candidate drug TEOA in rats.
AB  - 2alpha, 3alpha, 24-Trihydroxyurs-12-en-28-oic acid (TEOA) is a prominent ursane
      type triterpenoid isolated from the root of Actinidia deliciosa, which has
      numerous pharmacological activities. To date, there is no report on the
      pharmacokinetic characterization of TEOA in biological samples. A specific,
      sensitive and robust liquid chromatography-tandem mass spectrometry (LC-MS-MS)
      method is reported for the fast assay of TEOA in rat plasma. Plasma sample
      preparation was based on liquid-liquid extraction with ethyl acetate. The
      extracted samples were determined using LC-MS-MS coupled with an atmospheric
      pressure chemical ionization source in multiple-reaction monitoring scan mode.
      Chromatographic separation was achieved on a C18 Capcell PAK UG120 column (100 *
      4.6 mm, i.d., 5 um) using an isocratic elution mode with a total running time of
      2.8 min. The selected ion pairs m/z 471.3 -> 203.1 for the analyte and m/z 309.2 
      > 163.1 for internal standard were monitored in positive ionization mode for MS
      MS detection. This method has been fully validated and the results showed good
      linearity, precision, accuracy and recovery. A stability test was conducted under
      various sample preparation, analysis and storage conditions. The method was
      successfully applied for the pharmacokinetic study of TEOA in rat plasma after
      oral administration of 100 mg/kg TEOA.

PMID- 23139246
TI  - Scaling of weight for height in relation to risk of cancer at different sites in
      a cohort of Canadian women.
AB  - Many studies have examined the associations of body mass index (weight
      (kg)/height (m)(2)) with risk of various cancers. However, optimal scaling of
      weight for height may depend on the population studied. The authors used data
      from a large cohort study of women (Canadian National Breast Cancer Screening
      Study, 1980-2000; n = 89,835) to examine how the scaling of weight for height
      (W/H(x)) influenced the association with risk of 19 different cancers. Cox
      proportional hazards models were used to estimate the hazard ratio for each
      cancer site with W/H(x), with x increasing from 0 to 3.0 by increments of 0.1.
      The correlation between weight and W/H(x) decreased monotonically with increasing
      x, whereas W/H(x) was minimally correlated with height when x = 1.4. W/H(x)
      showed significant positive associations with postmenopausal breast cancer,
      endometrial cancer, kidney cancer, and lung cancer in never smokers. W/H(x) was
      inversely associated with lung cancer in ever smokers. The value of x for which
      W/H(x) produced the largest statistically significant hazard ratio ranged from
      0.8 (endometrial cancer) to 1.7 (postmenopausal breast cancer). For lung cancer
      in ever smokers, the inverse association was statistically significant for all
      values of x. These findings suggest that the scaling of weight for height may
      vary depending on the cancer site and that optimal scaling may be considerably
      different from W/H(2) or, alternatively, that a range of scaling should be
      considered when examining the association of body weight with risk of disease.

PMID- 23139247
TI  - Revealing the complexity of health determinants in resource-poor settings.
AB  - An epidemiologic systems analysis of diarrhea in children in Pakistan is
      presented. Application of additive Bayesian network modeling to 2005-2006 data
      from the Pakistan Social and Living Standards Measurement Survey reveals the
      complexity of child diarrhea as a disease system. The key distinction between
      standard analytical approaches, such as multivariable regression, and Bayesian
      network analyses is that the latter attempt to not only identify statistically
      associated variables but also, additionally and empirically, separate these into
      those directly and indirectly dependent upon the outcome variable. Such
      discrimination is vastly more ambitious but has the potential to reveal far more
      about key features of complex disease systems. Additive Bayesian network analyses
      across 41 variables from the Pakistan Social and Living Standards Measurement
      Survey identified 182 direct dependencies but with only 3 variables: 1) access to
      a dry pit latrine (protective; odds ratio = 0.67); 2) access to an atypical water
      source (protective; odds ratio = 0.49); and 3) no formal garbage collection
      (unprotective; odds ratio = 1.32), supported as directly dependent with the
      presence of diarrhea. All but 2 of the remaining variables were also, in turn,
      directly or indirectly dependent upon these 3 key variables. These results are
      contrasted with the use of a standard approach (multivariable regression).

PMID- 23139248
TI  - Adult asthma and risk of coronary heart disease, cerebrovascular disease, and
      heart failure: a prospective study of 2 matched cohorts.
AB  - Asthma has been associated with increased cardiovascular disease (CVD) risk. The
      authors ascertained the association of asthma with CVD and the roles that sex,
      concurrent allergy, and asthma medications may play in this association. They
      assembled a cohort of 203,595 Northern California adults with asthma and a
      parallel asthma-free referent cohort (matched 1:1 on age, sex, and
      race/ethnicity); both cohorts were followed for incident nonfatal or fatal CVD
      and all-cause mortality from January 1, 1996, through December 31, 2008. Each
      cohort was 66% female and 47% white. After adjustment for age, sex,
      race/ethnicity, cardiac risk factors, and comorbid allergy, asthma was associated
      with a 1.40-fold (95% confidence interval (CI): 1.35, 1.45) increased hazard of
      coronary heart disease, a 1.20-fold (95% CI: 1.15, 1.25) hazard of
      cerebrovascular disease, a 2.14-fold (95% CI: 2.06, 2.22) hazard of heart
      failure, and a 3.28-fold (95% CI: 3.15, 3.41) hazard of all-cause mortality.
      Stronger associations were noted among women. Comorbid allergy predicted CVD but
      did not synergistically increase the CVD risk associated with asthma. Only asthma
      patients using asthma medications (particularly those on oral corticosteroids
      alone or in combination) were at enhanced risk of CVD. In conclusion, asthma was
      prospectively associated with increased risk of major CVD. Modifying effects were
      noted for sex and asthma medication use but not for comorbid allergy.

PMID- 23139249
TI  - Association between use of specialty dietary supplements and C-reactive protein
      concentrations.
AB  - Laboratory evidence suggests that certain specialty dietary supplements have
      antiinflammatory properties, though evidence in humans remains limited. Data on a
      nationally representative sample of 9,947 adults from the 1999-2004 cycles of the
      National Health and Nutrition Examination Survey were used to assess the
      associations between specialty supplement use and inflammation, as measured by
      serum high-sensitivity C-reactive protein (hs-CRP) concentration. Using survey
      weighted multivariate linear regression, significant reductions in hs-CRP
      concentrations were associated with regular use of glucosamine (17%, 95%
      confidence interval (CI): 7, 26), chondroitin (22%, 95% CI: 8, 33), and fish oil
      (16%, 95% CI: 0.3, 29). No associations were observed between hs-CRP
      concentration and regular use of supplements containing methylsulfonylmethane,
      garlic, ginkgo biloba, saw palmetto, or pycnogenol. These results suggest that
      glucosamine and chondroitin supplements are associated with reduced inflammation
      in humans and provide further evidence to support an inverse association between
      use of fish oil supplements and inflammation. It is important to further
      investigate the potential antiinflammatory role of these supplements, as there is
      a need to identify safe and effective ways to reduce inflammation and the burden
      of inflammation-related diseases such as cancer and cardiovascular disease.

PMID- 23139250
TI  - Prospective study of serum 25-hydroxyvitamin D concentration and mortality in a
      Chinese population.
AB  - Prospective epidemiologic data on the association between vitamin D and mortality
      are limited, particularly in Asian populations. Among subjects in Linxian, China,
      the authors aimed to test whether baseline serum 25-hydroxyvitamin D (25(OH)D)
      concentrations in a prospective cohort were associated with all-cause mortality
      and cause-specific mortality rates over 24 years of follow-up (1986-2010). Serum
      25(OH)D concentrations were measured in 1,101 subjects using an immunoassay.
      Hazard ratios and 95% confidence intervals were calculated using Cox regression
      models that were adjusted for age, sex, tobacco smoking, alcohol drinking, and
      hypertension. The 25th, 50th, and 75th percentile concentrations of 25(OH)D were
      19.6, 31.9, and 48.4 nmol/L, respectively. During follow-up, 793 subjects died,
      including 279 who died of cerebrovascular accident, 217 who died of cancer, and
      200 cardiovascular disease deaths. All-cause mortality was not associated with
      25(OH)D concentrations using continuous models (for every 15 nmol/L, hazard ratio
      = 1.01, 95% confidence interval: 0.97, 1.05) or quartile models (fourth vs. first
      quartiles, hazard ratio = 1.06, 95% confidence interval: 0.87, 1.30; P for trend
      = 0.731). The authors also found no association with the cause-specific mortality
      outcomes. Results were similar for men and women. This study showed that
      prediagnostic serum 25(OH)D concentrations were not associated with all-cause or
      cause-specific mortality rates in this Chinese population who had low levels of
      vitamin D.

PMID- 23139251
TI  - Research on health-care quality improvement in low- and middle-income countries:
      is it a worthy investment?

PMID- 23139253
TI  - Clavicular bone tunnel malposition leads to early failures in coracoclavicular
      ligament reconstructions.
AB  - BACKGROUND: Modern techniques for the treatment of acromioclavicular (AC) joint
      dislocations have largely centered on free tendon graft reconstructions. Recent
      biomechanical studies have demonstrated that an anatomic reconstruction with 2
      clavicular bone tunnels more closely matches the properties of native
      coracoclavicular (CC) ligaments than more traditional techniques. No study has
      analyzed tunnel position in regard to risk of early failure. PURPOSE: To evaluate
      the effect of clavicular tunnel position in CC ligament reconstruction as a risk
      of early failure. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A
      retrospective review was performed of a consecutive series of CC ligament
      reconstructions performed with 2 clavicular bone tunnels and a free tendon graft.
      The population was largely a young, active-duty military group of patients.
      Radiographs were analyzed for the maintenance of reduction and location of
      clavicular bone tunnels using a picture archiving and communication system. The
      distance from the lateral border of the clavicle to the center of each bone
      tunnel was divided by the total clavicular length to establish a ratio. Medical
      records were reviewed for operative details and functional outcome. Failure was
      defined as loss of intraoperative reduction. RESULTS: The overall failure rate
      was 28.6% (8/28) at an average of 7.4 weeks postoperatively. Comparison of bone
      tunnel position showed that medialized bone tunnels were a significant predictor
      for early loss of reduction for the conoid (a ratio of 0.292 vs 0.248; P = .012)
      and trapezoid bone tunnels (a ratio of 0.171 vs 0.128; P = .004); this correlated
      to an average of 7 to 9 mm more medial in the reconstructions that failed.
      Reconstructions performed with a conoid ratio of >=0.30 were significantly more
      likely to fail (5/5, 100%) than were those performed lateral to a ratio of 0.30
      (3/23, 13.0%) (P < .01). There were no failures when the conoid ratio was <0.25
      (0/10, 0%). Conoid tunnel placement was also statistically significant for
      predicting return to duty in our active-duty population. CONCLUSION: Medial
      tunnel placement is a significant factor in risk for early failures when
      performing anatomic CC ligament reconstructions. Preoperative templating is
      recommended to evaluate optimal placement of the clavicular bone tunnels.
      Placement of the conoid tunnel at 25% of the clavicular length from the lateral
      border of the clavicle is associated with a lower rate of lost reduction and a
      higher rate of return to military duty.

PMID- 23139252
TI  - Sexual risk behavior among youth with perinatal HIV infection in the United
      States: predictors and implications for intervention development.
AB  - BACKGROUND: Factors associated with initiation of sexual activity among
      perinatally human immunodeficiency virus (HIV)-infected (PHIV(+)) youth, and the
      attendant potential for sexual transmission of antiretroviral (ARV) drug
      resistant HIV, remain poorly understood. METHODS: We conducted cross-sectional
      and longitudinal analyses of PHIV(+) youth aged 10-18 years (mean, 13.5 years)
      enrolled in the US-based Pediatric HIV/AIDS Cohort Study between 2007 and 2009.
      Audio computer-assisted self-interviews (ACASI) were used to collect sexual
      behavior information. RESULTS: Twenty-eight percent (95% confidence interval
      [CI], 23%-33%) (92/330) of PHIV(+) youth reported sexual intercourse (SI) (median
      initiation age, 14 years). Sixty-two percent (57/92) of sexually active youth
      reported unprotected SI. Among youth who did not report history of SI at
      baseline, ARV nonadherence was associated with sexual initiation during follow-up
      (adjusted hazard ratio, 2.87; 95% CI, 1.32-6.25). Youth living with a relative
      other than their biological mother had higher odds of engaging in unprotected SI
      than those living with a nonrelative. Thirty-three percent of youth disclosed
      their HIV status to their first sexual partner. Thirty-nine of 92 (42%) sexually
      active youth had HIV RNA >=5000 copies/mL after sexual initiation. Viral drug
      resistance testing, available for 37 of these 39 youth, identified resistance to
      nucleoside reverse transcriptase inhibitors in 62%, nonnucleoside reverse
      transcriptase inhibitors in 57%, protease inhibitors in 38%, and all 3 ARV
      classes in 22%. CONCLUSIONS: As PHIV(+) youth become sexually active, many engage
      in behaviors that place their partners at risk for HIV infection, including
      infection with drug-resistant virus. Effective interventions to facilitate youth
      adherence, safe sex practices, and disclosure are urgently needed.

PMID- 23139254
TI  - Integration of genetics into a systems model of electrocardiographic traits using
      HumanCVD BeadChip.
AB  - BACKGROUND: Electrocardiographic traits are important, substantially heritable
      determinants of risk of arrhythmias and sudden cardiac death. METHODS AND
      RESULTS: In this study, 3 population-based cohorts (n=10,526) genotyped with the
      Illumina HumanCVD Beadchip and 4 quantitative electrocardiographic traits (PR
      interval, QRS axis, QRS duration, and QTc interval) were evaluated for single
      nucleotide polymorphism associations. Six gene regions contained single
      nucleotide polymorphisms associated with these traits at P<10(-6), including
      SCN5A (PR interval and QRS duration), CAV1-CAV2 locus (PR interval), CDKN1A (QRS
      duration), NOS1AP, KCNH2, and KCNQ1 (QTc interval). Expression quantitative trait
      loci analyses of top associated single-nucleotide polymorphisms were undertaken
      in human heart and aortic tissues. NOS1AP, SCN5A, IGFBP3, CYP2C9, and CAV1 showed
      evidence of differential allelic expression. We modeled the effects of ion
      channel activity on electrocardiographic parameters, estimating the change in
      gene expression that would account for our observed associations, thus relating
      epidemiological observations and expression quantitative trait loci data to a
      systems model of the ECG. CONCLUSIONS: These association results replicate and
      refine the mapping of previous genome-wide association study findings for
      electrocardiographic traits, while the expression analysis and modeling
      approaches offer supporting evidence for a functional role of some of these loci
      in cardiac excitation/conduction.

PMID- 23139256
TI  - Aberrations in the epidermal growth factor receptor gene in 958 patients with
      diverse advanced tumors: implications for therapy.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) mutations are associated with
      the response to EGFR inhibitors in patients with non-small-cell lung cancer
      (NSCLC). We sought to investigate EGFR aberrations in patients with diverse
      advanced cancers. PATIENTS AND METHODS: Patients referred to the phase I clinic
      were evaluated for the presence of EGFR mutations and response to therapy.
      RESULTS: EGFR aberrations were detected in 34 of 958 patients (3.5%). Though EGFR
      mutations were most frequent in NSCLC (21 of 131, 16%), they were also present in
      a variety of other solid tumors (13 of 827 patients, 1.6%) including
      adrenocortical (1/10 patients), skin (1/24), breast (1/55), carcinoid (1/8),
      cholangiocarcinoma (1/20), head and neck (1/61), ovarian (1/84), parathyroid
      (1/1), salivary gland (1/20), renal (1/17), sarcoma (2/38), and thymic carcinomas
      (1/7). Of the 13 EGFR aberration-positive non-NSCLC patients (median number of
      prior systemic therapies = 3), 6 had treatment with an EGFR inhibitor. Two
      patients (diagnosis = parathyroid tumor and basal cell carcinoma) achieved stable
      disease (SD), lasting 6 and 7 months, respectively. CONCLUSION: We found EGFR
      aberrations in 1.6% of a large group of patients with diverse tumors other than
      NSCLC, and treatment with an EGFR inhibitor could be associated with prolonged
      SD.

PMID- 23139257
TI  - Risk factors for non-cancer health events in patients with head and neck squamous
      cell carcinoma.
AB  - BACKGROUND: Cancer progression and non-cancer-related morbidities can affect the
      quality of life and survival of patients with head and neck squamous cell
      carcinomas (HNSCC). The aim of this study was to investigate the risk factors for
      the development of non-cancer health events (NCHEs) in HNSCC. PATIENTS AND
      METHODS: The study involved 465 previously-untreated patients with HNSCC
      diagnosed between 2005 and 2009 at the Asan Medical Center. Non-cancer-associated
      morbidity was defined as readmission after treatment of HNSCC due to non-cancer
      related causes. NCHEs were defined as the occurrence of non-cancer-associated
      morbidity or mortality. The incidence and risk factors for NCHEs were analyzed.
      RESULTS: During the median follow-up of 47.6 months, non-cancer morbidity and
      mortality occurred in 83 (17.8%) and 25 patients (5.4%), respectively. Thirteen
      patients (52%) died from non-cancer-related causes with no previous admission for
      non-cancer causes. Multivariate analysis showed that the incidence of NCHEs was
      significantly associated with a Charlson comorbidity index >=1 and stage III/IV
      disease (P < 0.001). CONCLUSIONS: Patients with comorbidities and advanced
      diseases may be at higher risk of NCHEs. Because NCHEs are sometimes life
      threatening, every effort should be made to avoid unexpected non-cancer
      associated mortality in the HNSCC patients.

PMID- 23139258
TI  - The good, the bad and the ugly: a tale of miR-101, miR-21 and miR-155 in
      pancreatic intraductal papillary mucinous neoplasms.
AB  - BACKGROUND: This multicenter study evaluated three candidate microRNAs (miRNAs)
      (miR-21, miR-155 and miR-101) as potential biomarkers in intraductal papillary
      mucinous neoplasms (IPMNs) of the pancreas. PATIENTS AND METHODS: miRNA
      expression was quantified by quantitative RT-PCR in 86 laser-microdissected
      specimens, including 65 invasive IPMNs, 16 non-invasive IPMNs and 5 normal
      pancreatic ductal tissues. Univariate and multivariate analyses compared miRNAs
      and clinical parameters with overall (OS) and disease-free survival (DFS).
      RESULTS: miR-21 and miR-155 were up-regulated in invasive IPMNs compared with non
      invasive IPMNs, as well as in non-invasive IPMNs compared with normal tissues.
      Conversely, miR-101 levels were significantly higher in non-invasive IPMNs and
      normal tissues compared with invasive IPMNs. High levels of miR-21 were
      associated with worse OS [hazard ratio (HR) = 2.47, 95% confidence interval (CI)
      = 1.37-5.65, P = 0.0047]. Patients with high-miR-21 expression also had a shorter
      median DFS (10.9 versus 29.9 months, P = 0.01). Multivariate analysis confirmed
      miR-21 as independently prognostic for mortality and disease progression (death
      risk: HR = 3.3, 95% CI = 1.5-7.0, P = 0.02; progression risk: HR = 2.3, 95% CI =
      1.2-4.8, P = 0.02), as well as positive lymph-node status (death risk: HR = 2.6,
      95% CI = 1.1-6.3, P = 0.03; progression risk: HR = 2.2, 95% CI = 1.0-4.8, P =
      0.04). CONCLUSIONS: miR-21, miR-155 and miR-101 showed significant differences in
      invasive versus non-invasive IPMNs. miR-21 emerged as an independent prognostic
      biomarker in invasive IPMNs and should be validated in prospective studies.

PMID- 23139259
TI  - Neoadjuvant chemoradiotherapy with or without panitumumab in patients with wild
      type KRAS, locally advanced rectal cancer (LARC): a randomized, multicenter,
      phase II trial SAKK 41/07.
AB  - BACKGROUND: We conducted a randomized, phase II, multicenter study to evaluate
      the anti-epidermal growth factor receptor (EGFR) mAb panitumumab (P) in
      combination with chemoradiotherapy (CRT) with standard-dose capecitabine as
      neoadjuvant treatment for wild-type KRAS locally advanced rectal cancer (LARC).
      PATIENTS AND METHODS: Patients with wild-type KRAS, T3-4 and/or N+ LARC were
      randomly assigned to receive CRT with or without P (6 mg/kg). The primary end
      point was pathological near-complete or complete tumor response (pNC/CR), defined
      as grade 3 (pNCR) or 4 (pCR) histological regression by Dworak classification
      (DC). RESULTS: Forty of 68 patients were randomly assigned to P + CRT and 28 to
      CRT. pNC/CR was achieved in 21 patients (53%) treated with P + CRT [95%
      confidence interval (CI) 36%-69%] versus 9 patients (32%) treated with CRT alone
      (95% CI: 16%-52%). pCR was achieved in 4 (10%) and 5 (18%) patients, and pNCR in
      17 (43%) and 4 (14%) patients. In immunohistochemical analysis, most DC 3 cells
      were not apoptotic. The most common grade >=3 toxic effects in the P + CRT/CRT
      arm were diarrhea (10%/6%) and anastomotic leakage (15%/4%). CONCLUSIONS: The
      addition of panitumumab to neoadjuvant CRT in patients with KRAS wild-type LARC
      resulted in a high pNC/CR rate, mostly grade 3 DC. The results of both treatment
      arms exceeded prespecified thresholds. The addition of panitumumab increased
      toxicity.

PMID- 23139255
TI  - Novel loci associated with PR interval in a genome-wide association study of 10
      African American cohorts.
AB  - BACKGROUND: The PR interval, as measured by the resting, standard 12-lead ECG,
      reflects the duration of atrial/atrioventricular nodal depolarization.
      Substantial evidence exists for a genetic contribution to PR, including genome
      wide association studies that have identified common genetic variants at 9 loci
      influencing PR in populations of European and Asian descent. However, few studies
      have examined loci associated with PR in African Americans. METHODS AND RESULTS:
      We present results from the largest genome-wide association study to date of PR
      in 13 415 adults of African descent from 10 cohorts. We tested for association
      between PR (ms) and ~2.8 million genotyped and imputed single-nucleotide
      polymorphisms. Imputation was performed using HapMap 2 YRI and CEU panels. Study
      specific results, adjusted for global ancestry and clinical correlates of PR,
      were meta-analyzed using the inverse variance method. Variation in genome-wide
      test statistic distributions was noted within studies (lambda range: 0.9-1.1),
      although not after genomic control correction was applied to the overall meta
      analysis (lambda: 1.008). In addition to generalizing previously reported
      associations with MEIS1, SCN5A, ARHGAP24, CAV1, and TBX5 to African American
      populations at the genome-wide significance level (P<5.0 * 10(-8)), we also
      identified a novel locus: ITGA9, located in a region previously implicated in
      SCN5A expression. The 3p21 region harboring SCN5A also contained 2 additional
      independent secondary signals influencing PR (P<5.0 * 10(-8)). CONCLUSIONS: This
      study demonstrates the ability to map novel loci in African Americans as well as
      the generalizability of loci associated with PR across populations of African,
      European, and Asian descent.

PMID- 23139260
TI  - Final height in survivors of childhood cancer compared with Height Standard
      Deviation Scores at diagnosis.
AB  - BACKGROUND: Our study aimed to evaluate final height in a cohort of Dutch
      childhood cancer survivors (CCS) and assess possible determinants of final
      height, including height at diagnosis. PATIENTS AND METHODS: We calculated
      standard deviation scores (SDS) for height at initial cancer diagnosis and height
      in adulthood in a cohort of 573 CCS. Multivariable regression analyses were
      carried out to estimate the influence of different determinants on height SDS at
      follow-up. RESULTS: Overall, survivors had a normal height SDS at cancer
      diagnosis. However, at follow-up in adulthood, 8.9% had a height <=-2 SDS. Height
      SDS at diagnosis was an important determinant for adult height SDS. Children
      treated with (higher doses of) radiotherapy showed significantly reduced final
      height SDS. Survivors treated with total body irradiation (TBI) and craniospinal
      radiation had the greatest loss in height (-1.56 and -1.37 SDS, respectively).
      Younger age at diagnosis contributed negatively to final height. CONCLUSION:
      Height at diagnosis was an important determinant for height SDS at follow-up.
      Survivors treated with TBI, cranial and craniospinal irradiation should be
      monitored periodically for adequate linear growth, to enable treatment on time if
      necessary. For correct interpretation of treatment-related late effects studies
      in CCS, pre-treatment data should always be included.

PMID- 23139261
TI  - The role of radioactive iodine-125 seed localization in breast-conserving therapy
      following neoadjuvant chemotherapy.
AB  - BACKGROUND: Neoadjuvant chemotherapy (NAC) is increasingly used in the framework
      of breast-conserving therapy (BCT). Localization of the initial tumor is
      essential to guide surgical resection after NAC. This study describes the results
      obtained with I-125 seed localization in BCT including NAC. PATIENTS AND METHODS:
      Between January 2009 and December 2010, 85 patients treated with NAC and BCT
      after I-125 seed localization were included. Radiological and pathological
      response and resection margins were retrospectively evaluated. RESULTS: BCT was
      carried out in 85 patients without secondary local excisions. Nineteen patients
      with unifocal tumors and seven patients with multifocal tumors showed a complete
      pathological response (P = 0.18). Tumor-free resection margins were obtained in
      78 patients (50 patients with unifocal and 28 patients with multifocal tumors, P
      = 0.27). Focally involved margins were found in four patients (two patients with
      a unifocal and two patients with a multifocal tumor, P = 0.27). A subsequent
      mastectomy was carried out in three patients (two patients with multifocal
      tumors, P = 0.29). CONCLUSIONS: BCT after NAC can be carried out successfully
      after initial localization with I-125 seeds in both unifocal and multifocal
      breast tumors with complete resection rates of >90%.

PMID- 23139262
TI  - A randomized clinical trial of adjuvant chemotherapy with doxorubicin,
      ifosfamide, and cisplatin followed by radiotherapy versus radiotherapy alone in
      patients with localized uterine sarcomas (SARCGYN study). A study of the French
      Sarcoma Group.
AB  - BACKGROUND: There is no proven benefit of adjuvant treatment of uterine sarcoma
      (US). SARCGYN phase III study compared adjuvant polychemotherapy followed by
      pelvic radiotherapy (RT) (arm A) versus RT alone (arm B) conducted to detect an
      increase >= 20% of 3-year PFS. METHODS: Patients with FIGO stage <= III US,
      physiological age <= 65 years; chemotherapy: four cycles of doxorubicin 50
      mg/m&sup2; d1, ifosfamide 3 g/m&sup2;/day d1-2, cisplatin 75 mg/m&sup2; d3, (API)
      + G-CSF q 3 weeks. Study was stopped because of lack of recruitment. RESULTS:
      Eighty-one patients were included: 39 in arm A and 42 in arm B; 52 stage I, 16
      stage II, 13 stage III; 53 leiomyosarcomas, 9 undifferenciated sarcomas, 19
      carcinosarcomas. Gr 3-4 toxicity during API (/37 patients): thrombopenia (76%),
      febrile neutropenia (22%) with two toxic deaths; renal gr 3 (1 patient). After a
      median follow-up of 4.3 years, 41/81 patients recurred, 15 in arm A, 26 in arm B.
      The 3 years DFS is 55% in arm A, 41% in arm B (P = 0.048). The 3-year overall
      survival (OS) is 81% in arm A and 69% in arm B (P = 0.41). CONCLUSION: API
      adjuvant CT statistically increases the 3 year-DFS of patients with US.

PMID- 23139263
TI  - Functional proteomics characterization of residual breast cancer after
      neoadjuvant systemic chemotherapy.
AB  - BACKGROUND: The purpose of this study was to determine the functional proteomic
      characteristics of residual breast cancer and hormone receptor (HR)-positive
      breast cancer after neoadjuvant systemic chemotherapy, and their relationship
      with patient outcomes. METHODS: Reverse phase protein arrays of 76 proteins were
      carried out. A boosting approach in conjunction with a Cox proportional hazard
      model defined relapse predictors. A risk score (RS) was calculated with the sum
      of the coefficients from the final model. Survival outcomes and associations of
      the RS with relapse were estimated. An independent test set was used to validate
      the results. RESULTS: Test (n = 99) and validation sets (n = 79) were comparable.
      CoxBoost revealed a three-biomarker (CHK1pS345, Caveolin1, and RAB25) and a two
      biomarker (CD31 and Cyclin E1) model that correlated with recurrence-free
      survival (RFS) in all residual breast cancers and in HR-positive disease,
      respectively. Unsupervised clustering split patients into high- and low risk of
      relapse groups with different 3-year RFS (P <= 0.001 both). RS was a substantial
      predictor of RFS (P = 0.0008 and 0.0083) after adjustment for other substantial
      characteristics. Similar results were found in validation sets. CONCLUSIONS: We
      found models that independently predicted RFS in all residual breast cancer and
      in residual HR-positive disease that may represent potential targets of therapy
      in this resistant disease.

PMID- 23139264
TI  - Her2/neu testing in gastric cancer: evaluating the risk of sampling errors.
AB  - BACKGROUND: We evaluated the risk of sampling errors in specimens of biopsy size,
      which may be caused by heterogeneous overexpression of Her2/neu in gastric cancer
      (GC). PATIENTS AND METHODS: The study cohort comprised 454 gastrectomy patients
      with adenocarcinoma of the stomach or esophago-gastric junction. Tissue micro
      arrays (TMAs) served as 'biopsy procedure' and were generated from formalin-fixed
      and paraffin-embedded tissue: five tissue cylinders were collected randomly from
      each tumor, rendering 2230 core cylinders. These were compared with 454 whole
      tissue sections obtained from the same paraffin blocks. Her2/neu expression and
      gene amplification were analyzed by immunohistochemistry and in situ
      hybridization. The Her2/neu status was determined according to GC scoring system
      by two independent observers. RESULTS: In whole tissue sections, 37 (8.1%;
      observer 1) and 38 (8.4%; observer 2) of the GCs, and in the corresponding TMAs,
      28 (6.3%; observer 1) and 28 (6.3%; observer 2) of the GCs were classified as
      Her2/neu-positive (kappa value 98.5% and 96.2%; P < 0001). Comparison of whole
      tissue sections with corresponding TMAs showed a false-negative rate of 24% and a
      false-positive rate of 3% for TMAs. CONCLUSION: Assessment of the Her2/neu status
      in tissue biopsies carries a significant risk of sampling errors, thereby
      rendering patients unsuitable for treatment with trastuzumab.

PMID- 23139265
TI  - Efficacy and safety of adalimumab for the treatment of peripheral arthritis in
      spondyloarthritis patients without ankylosing spondylitis or psoriatic arthritis.
AB  - OBJECTIVES: To evaluate the efficacy and safety of adalimumab in patients with
      peripheral spondyloarthritis (SpA) not fulfilling the criteria for ankylosing
      spondylitis (AS) or psoriatic arthritis (PsA). METHODS: 40 patients with active
      peripheral SpA fulfilling the European Spondyloarthropathy Study Group or Amor
      criteria but not the criteria for AS or PsA were included in a randomised, double
      blind, placebo-controlled clinical trial. Patients were treated 1 : 1 with
      adalimumab or placebo for 12 weeks, followed by an open label extension up to
      week 24. Safety and efficacy measurements were performed every 6 weeks, with the
      patient's global assessment of disease activity at week 12 as the primary
      endpoint. RESULTS: At week 12, the patient's and physician's global assessment of
      disease activity, swollen joint count, Bath Ankylosing Spondylitis Disease
      Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS)
      and erythrocyte sedimentation rate improved significantly in the adalimumab group
      compared with the baseline values and compared with placebo. A similar
      improvement was seen upon adalimumab treatment from weeks 12 to 24 in the
      patients originally randomised to placebo, whereas the clinical response was
      maintained or even augmented at week 24 in the patients who received adalimumab
      from the start. ASDAS inactive disease and BASDAI50 responses were met in 42% of
      the adalimumab group versus 0%-5% in the placebo group at week 12 (p=0.001 and
      p=0.008, respectively), and were further increased at week 24. The number of
      adverse events was not different between the adalimumab and placebo groups.
      CONCLUSIONS: Adalimumab appears to be effective and well tolerated in SpA
      patients with peripheral arthritis, also in those patients not fulfilling the AS
      or PsA criteria.

PMID- 23139266
TI  - ASAS modification of the Berlin algorithm for diagnosing axial spondyloarthritis:
      results from the SPondyloArthritis Caught Early (SPACE)-cohort and from the
      Assessment of SpondyloArthritis international Society (ASAS)-cohort.
AB  - OBJECTIVE: To compare the original Berlin algorithm for diagnosing axial
      Spondyloarthritis (axSpA) with two modifications in the SPondyloArthritis Caught
      Early (SPACE)-cohort and the Assessment of SpondyloArthritis international
      Society (ASAS) axSpA criteria validation (ASAS)-cohort. METHODS: Patients in the
      SPACE-cohort (back pain >=3 months, <=2 years, onset <45 years) and the ASAS
      cohort (undiagnosed chronic back pain) were diagnosed according to three
      algorithms: original (inflammatory back pain (IBP) mandatory), modification 1
      (IBP defined by >=3/5 IBP-features instead of >=4/5) and modification 2 (IBP
      deleted as obligatory entry criterion, added as SpA-feature). Diagnosis by
      rheumatologist, ASAS axSpA criteria and likelihood ratio product were used as
      external standards to test the performance of the algorithms. RESULTS: SPACE
      cohort: Compared to the diagnosis by rheumatologist (either axSpA or no-axSpA),
      the original algorithm agreed in 120 patients (76.4%). Agreement decreased using
      modification 1 (119 patients; 75.8%), increased using modification 2 (125
      patients; 79.6%). Sensitivity increased from 66.2% (original) to 72.3%
      (modification 1) and 78.5% (modification 2). Specificity decreased more using
      modification 1 (83.7% to 78.3%) than when using modification 2 (83.7% to 79.6%).
      ASAS-cohort: Compared to the diagnosis by rheumatologist (either axSpA or no
      axSpA), the original algorithm agreed in 484 patients (70.7%). Agreement
      increased using modification 1 (520 patients; 75.9%) and modification 2 (548
      patients; 80.0%). Sensitivity increased from 65.3% (original) to 77.9%
      (modification 1) and 79.6% (modification 2). Specificity decreased more using
      modification 1 (79.2% to 72.2%) than when using modification 2 (79.2% to 75.6%).
      CONCLUSIONS: ASAS accepted a modified algorithm for diagnosing axSpA in which IBP
      is excluded as obligatory entry criterion and added as SpA-feature.

PMID- 23139267
TI  - Microscopic gut inflammation in axial spondyloarthritis: a multiparametric
      predictive model.
AB  - OBJECTIVE: To assess the rates and explore predictors of microscopic gut
      inflammation in a cohort of patients with axial and peripheral spondyloarthritis
      (SpA). METHODS: Ileocolonoscopy was performed in 65 patients with axial and
      peripheral SpA from the Gent Inflammatory Arthritis and spoNdylitis cohorT.
      Histopathological analysis and scoring were performed by an experienced
      pathologist. RESULTS: Overall, 46.2% of the patients with SpA showed microscopic
      gut inflammation. In axial SpA, the following parameters were independently
      associated with gut involvement: male sex (OR=8.9, p=0.035); high disease
      activity measured by the Bath Ankylosing Spondylitis Disease Activity Index
      (OR=2.05, p=0.032); restricted spinal mobility measured by the Bath Ankylosing
      Spondylitis Metrology Index (OR=1.94, p=0.009); and younger age (OR=0.85,
      p=0.013). No clear association was found for human leucocyte antigen-B27 status,
      presence of peripheral arthritis, enthesitis, uveitis, psoriasis, intake of non
      steroidal anti-inflammatory drugs and family history of SpA. The prevalence of
      gut inflammation in non-radiographic axial SpA and ankylosing spondylitis was
      comparable. CONCLUSIONS: The prevalence of microscopic gut inflammation in SpA
      remains unaltered over time. Younger age (shorter symptom duration), progressive
      disease, male sex and higher disease activity are independently associated with
      microscopic gut inflammation in axial SpA.

PMID- 23139268
TI  - Temporal synchrony deficits in amblyopia.
AB  - PURPOSE: Amblyopia is a developmental abnormality of visual cortex characterized
      by spatial processing deficits. Recently, it has been suggested that temporal
      processing also is affected. We investigated temporal sensitivity by measuring
      temporal synchrony sensitivity. METHODS: In Experiment 1, we used a contrast
      detection task to compare the detection of a flickering 3 Hz Gaussian blob to
      that of synchrony discrimination for a 180 degrees  phase shift. In Experiment 2,
      we measured synchrony thresholds directly by assessing the minimum degree of
      asynchrony that allowed subjects to discriminate which of 4 high-contrast
      Gaussian blobs was flickering asynchronously in time (synchrony thresholds).
      Three temporal frequencies (1, 2, and 3 Hz) and two element separations (1.25
      degrees  and 5 degrees ) were compared. RESULTS: In Experiment 1, we found that
      the amblyopes (mean age 19.90 +/- 8.59 years, range 11-48 years) exhibited a
      synchrony deficit only for the 1.25 degrees element separation in the amblyopic
      eye. In Experiment 2, we also found that the sensitivity for nonstrabismic (pure
      anismetropia) amblyopes (mean age 15.70 +/- 4.00 years, range 12-23 years) was
      reduced for all three temporal frequencies, whereas for strabismic (strabismus
      and anisometropia) amblyopes (mean age 24.10 +/- 10.03 years, range 11-48 years)
      it was reduced at 3 Hz only, possibly suggesting a different extent of impairment
      in temporal synchrony for different types of amblyopia. CONCLUSIONS: Our results
      suggest that amblyopes have a foveal low-level temporal processing deficit that
      could explain the previously reported deficit for figure-ground discrimination.

PMID- 23139269
TI  - Changes in mRNA expression of class 3 semaphorins and their receptors in the
      adult rat retino-collicular system after unilateral optic nerve injury.
AB  - PURPOSE: Increasing interest in the role of Class 3 Semaphorins (Sema3s) in
      plasticity and repair in the injured mammalian central nervous system prompted us
      to characterize changes in Sema3 expression after optic nerve (ON) injury.
      METHODS: We used unilateral ON transection (ONT) and ON crush (ONC) models in
      conjunction with quantitative polymerase chain reaction (qPCR), and in situ
      hybridization (ISH) to characterize postinjury changes in the expression of the
      Sema3s and their receptors in the rat retina, optic nerve, and superior
      colliculus (SC). RESULTS: We observed no changes in mRNA expression in axotomized
      retinas at 1 or 14 days after ONT, but there was a transient increase for Sema3b,
      Sema3f, L1cam, and Plxna3 at 3 days postinjury. There was no change in transcript
      expression in the deafferented contralateral SC 1 day following ONT, but there
      was a transient increase in Plxna2 at 3 days, and a decrease in Sema3e, L1cam,
      and Plxna4a mRNA levels by 14 days. There were also several changes in transcript
      expression in the unlesioned contralateral retina and ipsilateral SC that
      differed from those seen in axotomized retina and contralateral SC. At the injury
      site after ONC, there was a reduction in Sema3b and Sema3f mRNA at 6 hours,
      returning to control levels by 1 day, and a transient increase in SEMA3A
      immunoreactivity at 6 hours. CONCLUSIONS: These new data on Class 3 Semaphorins
      and their receptors provide more information about the complex reactive events
      that occur bilaterally in the retino-collicular system following unilateral adult
      ON injury.

PMID- 23139270
TI  - The choroid is thicker in angle closure than in open angle and control eyes.
AB  - PURPOSE: To study factors associated with choroidal thickness (CT) and to compare
      CT in angle closure (AC), open angle (OA), and normal eyes. METHODS: Forty
      controls, 106 OA, and 79 AC subjects underwent measurements of posterior CT by
      spectral domain-optical coherence tomography, and of intraocular pressure (IOP),
      blood pressure, axial length (AL), and central corneal thickness (CCT). RESULTS:
      CT was significantly greater in AC than in OA and normal eyes (HSD test, P <=
      0.05), but there was no significant difference between OA and normal CT; mean CT
      was 234, 235, and 318 MUm in the normal, OA, and AC groups, respectively. With
      multivariable analysis among all participants, thinner CT was associated with
      older age, longer AL, higher IOP, and thicker CCT (all P <= 0.03, R(2) = 0.45).
      Adjusting for other relevant variables, the AC group had a significantly greater
      CT than either the normal or the OA group (P = 0.003 and 0.03, respectively). In
      multivariable analysis including only OA and AC patients, neither cup-to-disc
      ratio nor visual field mean deviation were significantly associated with CT.
      Multivariable analysis for CT among normal eyes found longer AL to be associated
      with thinner CT (P = 0.04). CONCLUSIONS: AC eyes had significantly thicker CT
      than OA and normal eyes, even after adjusting for the shorter AL in AC eyes,
      supporting hypotheses that choroidal expansion contributes to the development of
      AC disease. Age, AL, CCT, and IOP were also significantly associated with CT,
      while severity of glaucoma damage was not.

PMID- 23139271
TI  - Effect of connective tissue growth factor on protein kinase expression and
      activity in human corneal fibroblasts.
AB  - PURPOSE: To investigate signal transduction pathways for connective tissue growth
      factor (CTGF) in human corneal fibroblasts (HCF). METHODS: Expression of 75
      kinases in cultures of serum-starved (HCF) were investigated using protein kinase
      screens, and changes in levels of phosphorylation of 31 different phosphoproteins
      were determined at 0, 5, and 15 minutes after treatment with CTGF. Levels of
      phosphorylation of three signal transducing phosphoproteins (extracellular
      regulated kinase 1 [ERK1], extracellular regulated kinase 2 [ERK2] [MAPKs], and
      signal transducer and activator of transcription 3 [STAT3]) were measured at nine
      time points after exposure to CTGF using Western immunoblots. Inhibition of Ras,
      MEK1/2 (MAPKK), and ERK1/2, on CTGF-stimulated fibroblast proliferation and
      collagen gel contraction was assessed using selective inhibitors
      farnesylthiosalicylic acid, PD-98059, and SB203580, respectively. RESULTS: Thirty
      two of the 75 kinases (43%) evaluated by the kinase screen were detected in
      extracts of quiescent HCF, suggesting these kinases are available to respond
      acutely to CTGF exposure. Addition of CTGF increased levels of phosphorylation of
      five phosphoproteins (ERK1 and 2, MEK1/2 [MAPKK], STAT3, and SAPK/JNK), and
      decreased levels of phosphorylation of 14 phosphoproteins (including protein
      kinases B and C) after 5 and 15 minutes. Further analysis of ERK1 and 2 and STAT3
      phosphorylation showed rapid increases within 1 minute of CTGF exposure that
      peaked between 5 and 10 minutes then returned to pretreatment levels by 30
      minutes. Treatment of HCF with selective inhibitors of Ras, MEK 1/2, and ERK1/2
      individually blocked both CTGF induced cell proliferation, and collagen gel
      contraction. CONCLUSIONS: Results from protein kinase screens and selective
      kinase inhibitors demonstrate Ras/MEK/ERK/STAT3 pathway is required for CTGF
      signaling in HCF.

PMID- 23139272
TI  - Age-related susceptibility to apoptosis in human retinal pigment epithelial cells
      is triggered by disruption of p53-Mdm2 association.
AB  - PURPOSE: Relatively little is known about the contribution of p53/Mdm2 pathway in
      apoptosis of retinal pigment epithelial (RPE) cells or its possible link to
      dysfunction of aging RPE or to related blinding disorders such as age-related
      macular degeneration (AMD). METHODS: Age-associated changes in p53 activation
      were evaluated in primary RPE cultures from human donor eyes of various ages.
      Apoptosis was evaluated by activation of caspases and DNA fragmentation. Gene
      specific small interfering RNA was used to knock down expression of p53. RESULTS:
      We observed that the basal rate of p53-dependent apoptosis increased in an age
      dependent manner in human RPE. The age-dependent increase in apoptosis was linked
      to alterations in several aspects of the p53 pathway. p53 phosphorylation Ser15
      was increased through the stimulation of ATM-Ser1981. p53 acetylation Lys379 was
      increased through the inhibition of SIRT1/2. These two posttranslational
      modifications of p53 blocked the sequestration of p53 by Mdm2, thus resulting in
      an increase in free p53 and of p53 stimulation of apoptosis through increased
      expression of PUMA (p53 upregulated modulator of apoptosis) and activation of
      caspase-3. Aged RPE also had reduced expression of antiapoptotic Bcl-2, which
      contributed to the increase in apoptosis. Of particular interest in these studies
      was that pharmacologic treatments to block p53 phosphorylation, acetylation, or
      expression were able to protect RPE cells from apoptosis. CONCLUSIONS: Our
      studies suggest that aging in the RPE leads to alterations of specific
      checkpoints in the apoptotic pathway, which may represent important molecular
      targets for the treatment of RPE-related aging disorders such as AMD.

PMID- 23139273
TI  - Analysis of continuous 24-hour intraocular pressure patterns in glaucoma.
AB  - PURPOSE: To present a method to analyze circadian intraocular pressure (IOP)
      patterns in glaucoma patients and suspects undergoing repeated continuous 24-hour
      IOP monitoring. METHODS: Forty patients with established (n = 19) or suspected
      glaucoma (n = 21) underwent ambulatory 24-hour IOP monitoring on two sessions 1
      week apart using a contact lens sensor (CLS). The CLS provides its output in
      arbitrary units (a.u.). A modified cosinor rhythmometry method was adapted to the
      CLS output to analyze 24-hour IOP patterns and their reproducibility.
      Nonparametric tests were used to study differences between sessions 1 and 2 (S1
      and S2). Patients pursued their routine daily activities and their sleep was
      uncontrolled. CLS data were used to assess sleep times. RESULTS: Complete 24-hour
      data from both sessions were available for 35 patients. Mean (SD) age of the
      patients was 55.8 +/- 15.5 years. The correlation of the cosinor fitting and
      measured CLS values was r = 0.38 (Spearman r; P < 0.001) for S1, r = 0.50 (P <
      0.001) for S2, whereas the correlation between S1 and S2 cosinor fittings was r =
      0.76 (P < 0.001). Repeated nocturnal acrophase was seen in 62.9% of patients;
      17.1% of patients had no repeatable acrophase. The average amplitude of the 24
      hour curve was 143.6 +/- 108.1 a.u. (S1) and 130.8 +/- 68.2 a.u. (S2) (P =
      0.936). CONCLUSIONS: Adapting the cosinor method to CLS data is a useful way for
      modeling the rhythmic nature of 24-hour IOP patterns and evaluating their
      reproducibility. Repeatable nocturnal acrophase was seen in 62.9% of patients.
      (ClinicalTrials.gov number, NCT01319617.).

PMID- 23139274
TI  - The effect of cone opsin mutations on retinal structure and the integrity of the
      photoreceptor mosaic.
AB  - PURPOSE: To evaluate retinal structure and photoreceptor mosaic integrity in
      subjects with OPN1LW and OPN1MW mutations. METHODS: Eleven subjects were
      recruited, eight of whom have been previously described. Cone and rod density was
      measured using images of the photoreceptor mosaic obtained from an adaptive
      optics scanning light ophthalmoscope (AOSLO). Total retinal thickness, inner
      retinal thickness, and outer nuclear layer plus Henle fiber layer (ONL+HFL)
      thickness were measured using cross-sectional spectral-domain optical coherence
      tomography (SD-OCT) images. Molecular genetic analyses were performed to
      characterize the OPN1LW/OPN1MW gene array. RESULTS: While disruptions in retinal
      lamination and cone mosaic structure were observed in all subjects, genotype
      specific differences were also observed. For example, subjects with "L/M
      interchange" mutations resulting from intermixing of ancestral OPN1LW and OPN1MW
      genes had significant residual cone structure in the parafovea (~25% of normal),
      despite widespread retinal disruption that included a large foveal lesion and
      thinning of the parafoveal inner retina. These subjects also reported a later
      onset, progressive loss of visual function. In contrast, subjects with the C203R
      missense mutation presented with congenital blue cone monochromacy, with retinal
      lamination defects being restricted to the ONL+HFL and the degree of residual
      cone structure (8% of normal) being consistent with that expected for the S-cone
      submosaic. CONCLUSIONS: The photoreceptor phenotype associated with OPN1LW and
      OPN1MW mutations is highly variable. These findings have implications for the
      potential restoration of visual function in subjects with opsin mutations. Our
      study highlights the importance of high-resolution phenotyping to characterize
      cellular structure in inherited retinal disease; such information will be
      critical for selecting patients most likely to respond to therapeutic
      intervention and for establishing a baseline for evaluating treatment efficacy.

PMID- 23139275
TI  - In vitro effects of bevacizumab treatment on newborn rat retinal cell
      proliferation, death, and differentiation.
AB  - PURPOSE: Vascular endothelial growth factor (VEGF) is an important signal protein
      in vertebrate nervous development, promoting neurogenesis, neuronal patterning,
      and glial cell growth. Bevacizumab, an anti-VEGF agent, has been extensively used
      for controlling pathological retinal neovascularization in adult and newborn
      patients, although its effect on the developing retina remains largely unknown.
      The purpose of this study was to investigate the effect of bevacizumab on cell
      death, proliferation, and differentiation in newborn rat retina. METHODS: Retinal
      explants of sixty 2-day-old Lister hooded rats were obtained after eye
      enucleation and maintained in culture media with or without bevacizumab for 2
      days. Immunohistochemical staining was assessed against proliferating cell
      nuclear antigen (PCNA, to detect cell proliferation); caspase-3 and beclin-1 (to
      investigate cell death); and vimentin and glial fibrillary acidic protein (GFAP,
      markers of glial cells). Gene expressions were quantified by real-time reverse
      transcription polymerase chain reaction. Results from treatment and control
      groups were compared. RESULTS: No significant difference in the staining
      intensity (on immunohistochemistry) of PCNA, caspase-3, beclin-1, and GFAP, or in
      the levels of PCNA, caspase-3, beclin-1, and vimentin mRNA was observed between
      the groups. However, a significant increase in vimentin levels and a significant
      decrease in GFAP mRNA expression were observed in bevacizumab-treated retinal
      explants compared with controls. CONCLUSIONS: Bevacizumab did not affect cell
      death or proliferation in early developing rat retina but appeared to interfere
      with glial cell maturation by increasing vimentin levels and downregulating GFAP
      gene expression. Thus, we suggest anti-VEGF agents be used with caution in
      developing retinal tissue.

PMID- 23139276
TI  - Inhibition of choroidal and corneal pathologic neovascularization by Plgf1-de
      gene transfer.
AB  - PURPOSE: Ocular neovascularization (NV), the primary cause of blindness,
      typically is treated via inhibition of VEGF-A activity. However, besides VEGF-A,
      other proteins of the same family, including VEGF-B and placental growth factor
      (PlGF, all together VEGFs), have a crucial role in the angiogenesis process. PlGF
      and VEGF, which form heterodimers if co-expressed, both are required for
      pathologic angiogenesis. We generated a PlGF1 variant, named PlGF1-DE, which is
      unable to bind and activate VEGFR-1, but retains the ability to form heterodimer.
      PlGF1-DE acts as dominant negative of VEGF-A and PlGF1wt through
      heterodimerization mechanism. The purpose of our study was to explore the
      therapeutic potential of Plgf1-de gene in choroid and cornea NV context. METHODS:
      In the model of laser-induced choroidal neovascularization (CNV), Plgf1-de gene,
      and as control Plgf1wt, LacZ, or gfp genes, were delivered using adeno-associated
      virus (AAV) vector by subretinal injection 14 days before the injury. After 7
      days CNV volume was assessed. Corneal NV was induced by scrape or suture
      procedures. Expression vectors for PlGF1wt or PlGF1-DE, and as control the empty
      vector pCDNA3, were injected in the mouse cornea after the vascularization
      insults. NV was evaluated with CD31 and LYVE-1 immunostaining. RESULTS: The
      expression of Plgf1-de induced significant inhibition of choroidal and corneal NV
      by reducing VEGF-A homodimer production. Conversely, the delivery of Plgf1wt,
      despite induced similar reduction of VEGF-A production, did not affect NV.
      CONCLUSIONS: Plgf1-de gene is a new therapeutic tool for the inhibition of VEGFs
      driven ocular NV.

PMID- 23139277
TI  - Topical administration of peroxiredoxin-6 on the cornea suppresses inflammation
      and neovascularization induced by ultraviolet radiation.
AB  - PURPOSE: To investigate the effect of topical administration of peroxiredoxin-6
      (PRDX6) on ultraviolet-induced corneal injury. METHODS: Corneal transparency and
      neovascularization were observed with a slit-lamp microscope and hematoxylin and
      eosin staining. The oxidative damage was determined with a commercial
      malondialdehyde (MDA) kit. The expressions of PRDX6, polymorphonuclear neutrophil
      (PMN), vascular endothelial growth factor (VEGF), and pigment epithelium-derived
      factor (PEDF) were determined by immunohistochemistry and Western blot. The
      expressions of genes related with antioxidant defense systems and cell apoptosis
      were detected by RT-PCR. RESULTS: The irradiated corneas appeared opaque and had
      high levels of MDA. Peripheral neovascularization and neutrophils appeared in the
      control and buffer-treated groups (with no treatment or PRDX6 diluent,
      respectively), whereas they were significantly suppressed in the PRDX6-treated
      group. The MDA content of the corneas in the PRDX6-treated group was
      significantly lower than that of the control and buffer-treated groups (P <
      0.05). In the PRDX6-treated group the immunoreactivity of VEGF was lower, and
      that of PEDF was higher, than that in the control and buffer-treated groups. In
      addition, there were expression correlations between PRDX6 and PMN, VEGF, PEDF.
      The expressions of genes related with antioxidant defense systems and cell
      apoptosis were significant different between buffer- and PRDX6-treated groups (P
      < 0.05). CONCLUSIONS: The topically administered PRDX6 maintained the homeostasis
      of corneal cells, reduced inflammation, and suppressed neovascularization and
      apoptosis under ultraviolet irradiation.

PMID- 23139279
TI  - Elucidation of the pathogenic mechanism of rhegmatogenous retinal detachment with
      proliferative vitreoretinopathy by proteomic analysis.
AB  - PURPOSE: To understand the molecular mechanisms of rhegmatogenous retinal
      detachment (RRD) with proliferative vitreoretinopathy (PVR), the vitreous
      proteome in RRD patients with severe PVR (grade C or D) was investigated.
      METHODS: The analysis of the vitreous proteome in RRD patients with PVR (n = 24)
      and donor samples (n = 8) was analyzed by one-dimensional (1D) SDS-PAGE and
      reverse-phase liquid chromatography tandem mass spectrometry (RP-LC-MS/MS). The
      data were analyzed using GeneGO MetaCore software. The research followed the
      tenets of the Declaration of Helsinki for the use of human subjects. RESULTS: In
      total, 516 and 364 proteins were identified in the vitreous of RRD patients with
      PVR and donor samples, including 48 overlapping proteins. In the PVR vitreous
      samples, the levels of extracellular (EC) proteins were increased and the levels
      of cytoskeleton proteins were decreased. In the pathologic process of PVR,
      inflammation was identified as an important GeneGo network. Furthermore, the
      complement and coagulation cascade was the essential pathway. Among the
      interaction network, the key node proteins in this network were p53 and
      transcription factor E2F1, respectively. CONCLUSIONS: 1D-SDS-PAGE coupled with RP
      LC-MS/MS is a valuable resource to aid in the characterization of the proteome of
      RRD patients with PVR. Inflammation is the important pathologic process of PVR,
      while complement and coagulation cascade was the crucial pathway. p53 and E2F1
      may be the new targets for successful treatment of RRD with PVR.

PMID- 23139278
TI  - Proteolytic processing of connective tissue growth factor in normal ocular
      tissues and during corneal wound healing.
AB  - PURPOSE: Connective tissue growth factor (CTGF) is a fibrogenic cytokine that is
      up-regulated by TGF-beta and mediates most key fibrotic actions of TGF-beta,
      including stimulation of synthesis of extracellular matrix and differentiation of
      fibroblasts into myofibroblasts. This study addresses the role of proteolytic
      processing of CTGF in human corneal fibroblasts (HCF) stimulated with TGF-beta,
      normal ocular tissues and wounded corneas. METHODS: Proteolytic processing of
      CTGF in HCF cultures, normal animal eyes, and excimer laser wounded rat corneas
      were examined by Western blot. The identity of a 21-kDa band was determined by
      tandem mass spectrometry, and possible alternative splice variants of CTGF were
      assessed by 5' Rapid Amplification of cDNA Ends (RACE). RESULTS: HCF stimulated
      by TGF-beta contained full length 38-kDa CTGF and fragments of 25, 21, 18, and 13
      kDa, while conditioned medium contained full length 38- and a 21-kDa fragment of
      CTGF that contained the middle "hinge" region of CTGF. Fragmentation of
      recombinant CTGF incubated in HCF extracts was blocked by the aspartate protease
      inhibitor, pepstatin. Normal mouse, rat, and rabbit whole eyes and rabbit ocular
      tissues contained abundant amounts of C-terminal 25- and 21-kDa fragments and
      trace amounts of 38-kDa CTGF, although no alternative transcripts were detected.
      All forms of CTGF (38, 25, and 21 kDa) were detected during healing of excimer
      ablated rat corneas, peaking on day 11. CONCLUSIONS: Proteolytic processing of 38
      kDa CTGF occurs during corneal wound healing, which may have important
      implications in regulation of corneal scar formation.

PMID- 23139280
TI  - Klf4 regulates the expression of Slurp1, which functions as an immunomodulatory
      peptide in the mouse cornea.
AB  - PURPOSE: The secreted Ly6/uPAR-related protein-1 (Slurp1), associated with the
      hyperkeratotic disorder mal de Meleda, is abundantly expressed in corneas. Here,
      we examine its corneal expression and functions. METHODS: Gene expression was
      quantified by quantitative PCR (qPCR), immunoblots, and immunofluorescent
      staining. Effect of Kruppel-like factor 4 (Klf4) on Slurp1 promoter was evaluated
      by chromatin immunoprecipitation (ChIP) and transient transfections. Adenoviral
      vectors were used to express Slurp1 in corneas. Leukocytic infiltration in
      bacterial lipopolysaccharide (LPS)-, herpes simplex virus type 1 (HSV-1)-, or
      adenovirus (serotype 5)-treated mouse corneas was characterized by flow
      cytometry. RESULTS: Corneal expression of Slurp1 increased sharply upon mouse
      eyelid opening, concurrent with the elevated expression of Klf4. Slurp1 was
      significantly decreased in Klf4 conditional null (Klf4CN) corneas that displayed
      elevated expression of cytokines and cytokine receptors, as well as neutrophil
      influx consistent with a proinflammatory environment. In additional models of
      corneal inflammation, Slurp1 expression was abrogated within 24 hours of LPS
      injection or HSV-1 or adenoviral infection, accompanied by a predominantly
      neutrophilic infiltrate. Neutrophilic infiltration was enhanced in HSV-1-infected
      Klf4CN corneas lacking Slurp1. SLURP1 promoter activity was stimulated by KLF4,
      suppressed by IL-4, IL-13, and TNFalpha, and unperturbed by IFN-gamma. Slurp1
      downregulation and neutrophil influx were comparable in HSV-1-infected wild-type
      (WT) and Ifng-/- mouse corneas. Mouse corneas infected with Slurp1-expressing
      adenoviral vectors displayed reduced signs of inflammation and restricted
      neutrophilic infiltration compared with those infected with control vectors.
      CONCLUSIONS: Klf4 regulates the expression of Slurp1, a key immunomodulatory
      peptide that is abundantly expressed in healthy corneas and is downregulated in
      proinflammatory conditions.

PMID- 23139281
TI  - The role of axial resolution of optical coherence tomography on the measurement
      of corneal and epithelial thicknesses.
AB  - PURPOSE: Our purpose was to investigate the role of the axial resolution of
      optical coherence tomography (OCT) on the measurement of corneal and epithelial
      thickness by evaluating the repeatability and agreement among different OCT
      devices with different axial resolutions. METHODS: twenty right eyes of 20
      healthy subjects (AGE: 22.3 +/- 1.3 years) and 18 eyes of 18 patients (age: 25.7
      +/- 6.8 years) after laser in situ keratomileusis (LASIK) refractive surgery were
      tested. Each subject was imaged using four OCT devices: ultra-high resolution OCT
      (UHR-OCT), ultra-long scan depth OCT (UL-OCT), commercial RTVue, and Visante. The
      OCT images obtained from UHR-OCT, UL-OCT, and RTVue were processed with a custom
      automated algorithm for measuring the central corneal thickness (CCT) and central
      epithelial thickness (ET). CCT measurements from pachymetry maps that were
      generated by RTVue and Visante were also obtained. RESULTS: For both groups, the
      CCT and ET measured by UHR-OCT and UL-OCT were highly correlated with RTVue when
      the automated image processing algorithm was used. The CCT measurements from the
      RTVue and Visante pachymetry were thicker than those measurements obtained from
      the automatic algorithm. The coefficient of repeatability was less than 4.9 MUm
      in the healthy subjects and 7.9 MUm in the LASIK patients, and the associated
      intraclass correlation coefficient (ICC) was greater than 0.992 in both groups
      for the CCT measurements. For the ET measurements using UHR-OCT, UL-OCT and
      RTVue, the coefficient of repeatability was less than 2.2 MUm in the healthy
      subjects and 4.8 MUm in the LASIK patients with an ICC that was greater than
      0.84. CONCLUSIONS: The axial resolution of OCT may play a role in determining the
      precision with which the CCT and the ET can be measured, although it may not
      affect the measurement of results.

PMID- 23139283
TI  - MicroRNAs control vascular endothelial growth factor signaling.

PMID- 23139282
TI  - Temporal development of retinal arteriolar endothelial dysfunction in porcine
      type 1 diabetes.
AB  - PURPOSE: Although hyperglycemia is implicated in retinal vascular dysfunction
      associated with the development of diabetic retinopathy, the temporal influence
      of hyperglycemia on retinal arteriolar reactivity remains unclear. Development of
      a large animal model of diabetes relevant to the human retina for evaluation of
      vascular function is also lacking. Herein, we examined nitric oxide (NO)-mediated
      dilation and endothelin-1 (ET-1)-induced constriction in retinal arterioles at
      various time periods in a porcine model of type 1 diabetes. METHODS: Retinal
      arterioles were isolated from streptozocin-induced diabetic pigs (2, 6, and 12
      weeks of hyperglycemia, 427 +/- 23 mg/dL) and age-matched control pigs (73 +/- 4
      mg/dL), and then cannulated and pressurized for vasoreactivity study using
      videomicroscopic techniques. RESULTS: Retinal arterioles isolated from control
      and diabetic pigs developed comparable levels of myogenic tone. The endothelium
      dependent NO-mediated vasodilations to bradykinin and stepwise increases in
      luminal flow were significantly reduced within 2 weeks of hyperglycemia. The
      inhibitory effect was comparable following 6 and 12 weeks of hyperglycemia.
      However, the endothelium-independent vasodilation to sodium nitroprusside was
      unaffected. Constriction of retinal arterioles to ET-1 was unaltered at all time
      periods of hyperglycemia. CONCLUSIONS: Our findings provide the first direct
      evidence for selective impairment of endothelium-dependent NO-mediated dilation
      of retinal arterioles within 2 weeks of hyperglycemia in a pig model of diabetes.
      By contrast, the ability of arteriolar smooth muscle to dilate to NO donor or
      contract to ET-1 was unaffected throughout the study period. This endothelial
      vasodilator dysfunction during early diabetes may contribute to development of
      retinopathy with chronic hyperglycemia.

PMID- 23139284
TI  - Restraint stress restrains cholesterol in the intestine.

PMID- 23139285
TI  - MicroRNAs micromanage themselves.
AB  - Since their discovery not long ago, microRNAs (miRNAs) have been extensively
      studied in hundreds of laboratories around the world. Initially thought of as
      merely cytoplasmic repressors of mRNA expression, it has since become more
      apparent that they also play regulatory roles in the nucleus. A recent study
      published in Nature introduces novel concepts in both miRNA regulation and
      function by showing that the let-7 miRNA regulates its own expression.

PMID- 23139286
TI  - Cardiorenal syndrome: the emerging role of protein-bound uremic toxins.
AB  - Cardiorenal syndrome is a condition in which a complex interrelationship between
      cardiac dysfunction and renal dysfunction exists. Despite advances in treatment
      of both cardiovascular and kidney disease, cardiorenal syndrome remains a major
      global health problem. Characteristic of the pathophysiology of cardiorenal
      syndrome is bidirectional cross-talk; mediators/substances activated by the
      disease state of 1 organ can play a role in worsening dysfunction of the other by
      exerting their biologically harmful effects, leading to the progression of the
      syndrome. Accumulation of uremic toxins is a hallmark of renal excretory
      dysfunction. Removal of some toxins by conventional dialysis is particularly
      problematic because of their high protein binding. In this review, we demonstrate
      that protein-bound uremic toxins may play an important role in progression of
      cardiovascular disease in the setting of chronic kidney disease. The highly
      protein-bound uremic toxin indoxyl sulfate has emerged as a potent toxin
      adversely affecting both the kidney and heart. Direct cardiac effects of this
      toxin have been recently demonstrated both in vitro and in vivo. Specifically,
      potent fibrogenic and prohypertrophic effects, as well as oxidative stress
      inducing effects, appear to play a central role in both renal and cardiac
      pathology. Many of these adverse effects can be suppressed by use of a gut
      adsorbent, AST-120. Potential mechanisms underlying indoxyl sulfate-induced
      cardiorenal fibrosis are discussed. Future research and clinical implications
      conclude this review.

PMID- 23139287
TI  - Genetic Cre-loxP assessment of epicardial cell fate using Wt1-driven Cre alleles.
AB  - RATIONALE: Wt1-Cre-based tools are important reagents for studying epicardial
      cell fate and gene function. OBJECTIVE: To better describe the properties of Wt1
      Cre-based tools to enhance their use in Cre-loxP-based experiments. METHODS AND
      RESULTS: In contrast to recently reported results, we show that constitutive
      Wt1(GFPCre) in combination with certain Cre-activated reporters can be used to
      trace (pro) epicardial cell fate. Wt1(CreERT2) can be efficiently induced by
      tamoxifen administration. We show substantial labeling of coronary endothelial
      cells when induction is performed at late but not early stages of heart
      development. CONCLUSIONS: Wt1-based Cre alleles are useful tools for genetic
      lineage tracing of epicardial cells and mesothelium of other organs. Using these
      tools with proper understanding of their properties and limitations enables
      genetic labeling of epicardial cells and their derivatives.

PMID- 23139290
TI  - Identification of a novel insertion sequence element associated with carbapenem
      resistance and the development of fluoroquinolone resistance in Acinetobacter
      radioresistens.

PMID- 23139291
TI  - Upregulating reverse cholesterol transport with cholesteryl ester transfer
      protein inhibition requires combination with the LDL-lowering drug berberine in
      dyslipidemic hamsters.
AB  - OBJECTIVE: This study aimed to investigate whether cholesteryl ester transfer
      protein inhibition promotes in vivo reverse cholesterol transport in dyslipidemic
      hamsters. METHODS AND RESULTS: In vivo reverse cholesterol transport was measured
      after an intravenous injection of (3)H-cholesteryl-oleate-labeled/oxidized low
      density lipoprotein particles ((3)H-oxLDL), which are rapidly cleared from plasma
      by liver-resident macrophages for further (3)H-tracer egress in plasma, high
      density lipoprotein (HDL), liver, and feces. A first set of hamsters made
      dyslipidemic with a high-fat and high-fructose diet was treated with vehicle or
      torcetrapib 30 mg/kg (TOR) over 2 weeks. Compared with vehicle, TOR increased
      apolipoprotein E-rich HDL levels and significantly increased (3)H-tracer
      appearance in HDL by 30% over 72 hours after (3)H-oxLDL injection. However, TOR
      did not change (3)H-tracer recovery in liver and feces, suggesting that uptake
      and excretion of cholesterol deriving from apolipoprotein E-rich HDL is not
      stimulated. As apoE is a potent ligand for the LDL receptor, we next evaluated
      the effects of TOR in combination with the LDL-lowering drug berberine, which
      upregulates LDL receptor expression in dyslipidemic hamsters. Compared with TOR
      alone, treatment with TOR+berberine 150 mg/kg resulted in lower apolipoprotein E
      rich HDL levels. After (3)H-oxLDL injection, TOR+berberine significantly
      increased (3)H-tracer appearance in fecal cholesterol by 109%. CONCLUSIONS: Our
      data suggest that cholesteryl ester transfer protein inhibition alone does not
      stimulate reverse cholesterol transport in dyslipidemic hamsters and that
      additional effects mediated by the LDL-lowering drug berberine are required to
      upregulate this process.

PMID- 23139292
TI  - Skin autofluorescence as a measure of advanced glycation end products deposition
      is elevated in peripheral artery disease.
AB  - OBJECTIVE: Evidence for an important role of advanced glycation end products
      (AGEs) in the development of atherosclerosis and cardiovascular disease beyond
      diabetes mellitus and renal disease is growing. Skin autofluorescence (SAF) is a
      validated noninvasive measure of tissue AGEs. We hypothesized that SAF is
      elevated in peripheral artery disease (PAD). METHODS AND RESULTS: A case-control
      study was performed in 492 patients with PAD and 164 controls, matched for age
      (mean 66 +/- 10 years) and presence of diabetes mellitus. Cardiovascular risk
      factors and comorbidity (coronary artery disease, cerebrovascular disease,
      abdominal aortic aneurysm) were assessed. SAF was measured with the AGE Reader.
      SAF was higher in patients compared with controls: geometric mean 2.77 (95%
      confidence interval [CI], 2.71-2.83) versus 2.44 (95% CI, 2.35-2.53) arbitrary
      units, P=0.4*10(-8). In logistic regression, the adjusted odds ratio for the
      presence of PAD was 2.47 (95% CI, 1.66-3.69) per 1 unit increase of SAF. PAD
      patients with cardiovascular comorbidity had a higher SAF compared with those
      without: geometric mean 2.93 (95% CI, 2.85-3.02) versus 2.63 (95% CI, 2.55-2.71)
      arbitrary units, P=0.4*10(-6), also after correction for confounders. Regression
      analysis showed that age, smoking, diabetes mellitus, chronic kidney disease, and
      a history of cerebrovascular disease or abdominal aortic aneurysm were
      independently associated with SAF in the patients with PAD. CONCLUSIONS:
      Accumulation of tissue AGEs is increased in patients with PAD, independent of
      cardiovascular risk factors and comorbidity, although these conditions are
      associated with a further increase. These findings underscore the importance of
      AGEs in PAD, irrespective of the presence of diabetes mellitus and renal
      insufficiency.

PMID- 23139293
TI  - ACAT inhibition reduces the progression of preexisting, advanced atherosclerotic
      mouse lesions without plaque or systemic toxicity.
AB  - OBJECTIVE: Acyl-CoA:cholesterol acyltransferase (ACAT) converts cholesterol to
      cholesteryl esters in plaque foam cells. Complete deficiency of macrophage ACAT
      has been shown to increase atherosclerosis in hypercholesterolemic mice because
      of cytotoxicity from free cholesterol accumulation, whereas we previously showed
      that partial ACAT inhibition by Fujirebio compound F1394 decreased early
      atherosclerosis development. In this report, we tested F1394 effects on
      preestablished, advanced lesions of apolipoprotein-E-deficient mice. METHODS AND
      RESULTS: Apolipoprotein-E-deficient mice on Western diet for 14 weeks developed
      advanced plaques, and were either euthanized (Baseline), or continued on Western
      diet with or without F1394 and euthanized after 14 more weeks. F1394 was not
      associated with systemic toxicity. Compared with the baseline group, lesion size
      progressed in both groups; however, F1394 significantly retarded plaque
      progression and reduced plaque macrophage, free and esterified cholesterol, and
      tissue factor contents compared with the untreated group. Apoptosis of plaque
      cells was not increased, consistent with the decrease in lesional free
      cholesterol. There was no increase in plaque necrosis and unimpaired
      efferocytosis (phagocytic clearance of apoptotic cells). The effects of F1394
      were independent of changes in plasma cholesterol levels. CONCLUSIONS: Partial
      ACAT inhibition by F1394 lowered plaque cholesterol content and had other
      antiatherogenic effects in advanced lesions in apolipoprotein-E-deficient mice
      without overt systemic or plaque toxicity, suggesting the continued potential of
      ACAT inhibition for the clinical treatment of atherosclerosis, in spite of recent
      trial data.

PMID- 23139294
TI  - Sildenafil potentiates bone morphogenetic protein signaling in pulmonary arterial
      smooth muscle cells and in experimental pulmonary hypertension.
AB  - OBJECTIVE: Mutations in the bone morphogenetic protein type II receptor (BMPR-II)
      are responsible for the majority of cases of heritable pulmonary arterial
      hypertension (PAH), and BMPR-II deficiency contributes to idiopathic and
      experimental forms of PAH. Sildenafil, a potent type-5 nucleotide-dependent
      phosphodiesterase inhibitor, is an established treatment for PAH, but whether
      sildenafil affects bone morphogenetic protein (BMP) signaling in the pulmonary
      circulation remains unknown. METHODS AND RESULTS: Studies were undertaken in
      human pulmonary arterial smooth muscle cells (PASMCs) and in vivo in the
      monocrotaline rat model of PAH. In PASMCs, sildenafil enhanced BMP4-induced
      phosphorylation of Smad1/5, Smad nuclear localization, and Inhibitor of DNA
      binding protein 1 gene and protein expression. This effect was mimicked by 8
      bromo-cyclic GMP. Pharmacological inhibition or small interfering RNA knockdown
      of cyclic GMP-dependent protein kinase I inhibited the effect of sildenafil on
      BMP signaling. In functional studies, we observed that sildenafil potentiated the
      antiproliferative effects of BMP4 on PASMC proliferation. Furthermore, sildenafil
      restored the antiproliferative response to BMP4 in PASMCs harboring mutations in
      BMPR-II. In the monocrotaline rat model of PAH, which is characterized by BMPR-II
      deficiency, sildenafil prevented the development of pulmonary hypertension and
      vascular remodeling, and partly restored Smad1/5 phosphorylation and Inhibitor of
      DNA binding protein 1 gene expression in vivo in monocrotaline exposed rat lungs.
      CONCLUSIONS: Sildenafil enhances canonical BMP signaling via cyclic GMP and
      cyclic GMP-dependent protein kinase I in vitro and in vivo, and partly restores
      deficient BMP signaling in BMPR-II mutant PASMCs. Our findings demonstrate a
      novel mechanism of action of sildenafil in the treatment of PAH and suggest that
      targeting BMP signaling may be beneficial in this disease.

PMID- 23139295
TI  - Adiponectin and long-term mortality in coronary artery disease participants and
      controls.
AB  - OBJECTIVE: Despite cardioprotective properties, studies investigating adiponectin
      as a cardiovascular disease marker led to conflicting results. We investigated in
      participants with stable coronary artery disease (CAD) and controls whether serum
      adiponectin was associated with long-term mortality, considering varying degrees
      of CAD severity. METHODS AND RESULTS: A case-control design with prospective
      median follow-up of 8.1 years was used. Survival rates among 715 CAD men (aged 45
      74 years) in increasing quartiles of serum adiponectin values were 87.5%, 85.6%,
      76.4%, and 67.6%, respectively (P<0.001). Survival rates in 782 controls with
      adiponectin <9.1 ug/mL and >=9.1 ug/mL (third quartile) were 95.3% and 91.0%,
      respectively (P=0.035). Adiponectin concentration above the highest quartile was
      associated with an increased risk of total and cardiovascular disease mortality
      in CAD patients (P=0.001 and P=0.001) and controls (P=0.02 and P=0.004). The
      associations among high adiponectin, total mortality, and cardiovascular disease
      mortality remained significant after multivariate adjustments for metabolic,
      cardiac, and CAD severity variables. No significant interaction was found among
      CAD patients, controls, and the relationship of adiponectin with mortality.
      CONCLUSIONS: High serum adiponectin is a predictor of mortality, particularly
      from cardiovascular disease. This prognostic value remains significant whatever
      the severity of the CAD and the metabolic status and is not different among
      people with and without CAD.

PMID- 23139297
TI  - Chronic ischemic mitral regurgitation: insights into Pandora's box.

PMID- 23139298
TI  - Speak up for science funding.

PMID- 23139303
TI  - U.S. hurricane. Scientists assess damage from Sandy's deadly punch.

PMID- 23139296
TI  - Comprehensive annular and subvalvular repair of chronic ischemic mitral
      regurgitation improves long-term results with the least ventricular remodeling.
AB  - BACKGROUND: Undersized ring annuloplasty for ischemic mitral regurgitation (MR)
      is associated with variable results and >30% MR recurrence. We tested whether
      subvalvular repair by severing second-order mitral chordae can improve
      annuloplasty by reducing papillary muscle tethering. METHODS AND RESULTS:
      Posterolateral myocardial infarction known to produce chronic remodeling and MR
      was created in 28 sheep. At 3 months, sheep were randomized to sham surgery
      versus isolated undersized annuloplasty versus isolated bileaflet chordal cutting
      versus the combined therapy (n=7 each). At baseline, chronic myocardial
      infarction (3 months), and euthanasia (6.6 months), we measured left ventricular
      (LV) volumes and ejection fraction, wall motion score index, MR regurgitation
      fraction and vena contracta, mitral annulus area, and posterior leaflet
      restriction angle (posterior leaflet to mitral annulus area) by 2-dimensional and
      3-dimensional echocardiography. All groups were comparable at baseline and
      chronic myocardial infarction, with mild to moderate MR (MR vena contracta, 4.6+/
      0.1 mm; MR regurgitation fraction, 24.2+/-2.9%) and mitral annulus dilatation
      (P<0.01). At euthanasia, MR progressed to moderate to severe in controls but
      decreased to trace with ring plus chordal cutting versus trace to mild with
      chordal cutting alone versus mild to moderate with ring alone (MR vena contracta,
      5.9+/-1.1 mm in controls, 0.5+/-0.08 with both, 1.0+/-0.3 with chordal cutting
      alone, 2.0+/-0.4 with ring alone; P<0.01). In addition, LV end-systolic volume
      increased by 108% in controls versus 28% with ring plus chordal cutting, less
      than with each intervention alone (P<0.01). In multivariate analysis, LV end
      systolic volume and mitral annulus area most strongly predicted MR (r(2)=0.82,
      P<0.01). CONCLUSIONS: Comprehensive annular and subvalvular repair improves long
      term reduction of both chronic ischemic MR and LV remodeling without decreasing
      global or segmental LV function at follow-up.

PMID- 23139304
TI  - Archaeology. Did pulses of climate change drive the rise and fall of the Maya?

PMID- 23139305
TI  - Bioengineering. Lung-on-a-chip breathes new life into drug discovery.

PMID- 23139306
TI  - Malaria. As drug pilot wraps up, a lively debate about its future.

PMID- 23139307
TI  - Planetary science. Question of martian methane is still up in the air.

PMID- 23139309
TI  - Meteorology. One Sandy forecast a bigger winner than others.

PMID- 23139308
TI  - Meteorology. Weather forecasts slowly clearing up.

PMID- 23139310
TI  - Science in Europe. Poor but smart.

PMID- 23139311
TI  - Limits to religious conservation efforts.

PMID- 23139312
TI  - Credit due to Peter Higgs.

PMID- 23139313
TI  - Evolution's misleading language.

PMID- 23139314
TI  - Comment on "Glacial survival of boreal trees in northern Scandinavia".
AB  - Parducci et al. (Reports, 2 March 2012, p. 1083) fail to present convincing
      evidence for glacial survival of Pinus and Picea in northern Scandinavia. Their
      methodology does not exclude contamination. Additionally, they should consider
      the lack of suitable habitats, the apparent extinction of both taxa after
      deglacial warming, and alternative hypotheses for the distribution of the Picea
      genetic marker haplotype A.

PMID- 23139317
TI  - Patent law. Law and science collide over human gene patents.

PMID- 23139318
TI  - Immunology. A decorated virus cannot hide.

PMID- 23139319
TI  - Evolution. Constraints on sexual selection.

PMID- 23139320
TI  - Epidemiology. Emerging disease or diagnosis?

PMID- 23139321
TI  - Chemistry. Driving the formation of molecular knots.

PMID- 23139322
TI  - Chemistry. A single-molecule engine.

PMID- 23139323
TI  - Climate change. Constraining cloud feedbacks.

PMID- 23139324
TI  - Molecular biology. Epigenetic islands in a genetic ocean.

PMID- 23139325
TI  - Hepcidin and the iron-infection axis.
AB  - Iron lies at the center of a battle for nutritional resource between higher
      organisms and their microbial pathogens. The iron status of the human host
      affects the pathogenicity of numerous infections including malaria, HIV-1, and
      tuberculosis. Hepcidin, an antimicrobial-like peptide hormone, has emerged as the
      master regulator of iron metabolism. Hepcidin controls the absorption of dietary
      iron and the distribution of iron among cell types in the body, and its synthesis
      is regulated by both iron and innate immunity. We describe how hepcidin
      integrates signals from diverse physiological inputs, forming a key molecular
      bridge between iron trafficking and response to infection.

PMID- 23139326
TI  - An interacting binary system powers precessing outflows of an evolved star.
AB  - Stars are generally spherical, yet their gaseous envelopes often appear
      nonspherical when ejected near the end of their lives. This quirk is most notable
      during the planetary nebula phase, when these envelopes become ionized.
      Interactions among stars in a binary system are suspected to cause the asymmetry.
      In particular, a precessing accretion disk around a companion is believed to
      launch point-symmetric jets, as seen in the prototype Fleming 1. Our finding of a
      post-common-envelope binary nucleus in Fleming 1 confirms that this scenario is
      highly favorable. Similar binary interactions are therefore likely to explain
      these kinds of outflows in a large variety of systems.

PMID- 23139327
TI  - Polarity-switching top coats enable orientation of sub-10-nm block copolymer
      domains.
AB  - Block copolymers (BCPs) must necessarily have high interaction parameters (chi),
      a fundamental measure of block incompatibility, to self-assemble into sub-10
      nanometer features. Unfortunately, a high chi often results from blocks that have
      disparate interfacial energies, which makes the formation of useful thin-film
      domain orientations challenging. To mitigate interfacial forces, polymers
      composed of maleic anhydride and two other components have been designed as top
      coats that can be spin-coated from basic aqueous solution in the ring-opened,
      acid salt form. When baked, the anhydride reforms and switches polarity to create
      a neutral layer enabling BCP feature alignment not possible by thermal annealing
      alone. Top coats were applied to the lamella-forming block copolymers
      poly(styrene-block-trimethylsilylstyrene-block-styrene) and
      poly(trimethylsilylstyrene-block-lactide), which were thermally annealed to
      produce perpendicular features with linewidths of 15 and 9 nanometers,
      respectively.

PMID- 23139328
TI  - Driving a macroscopic oscillator with the stochastic motion of a hydrogen
      molecule.
AB  - Energy harvesting from noise is a paradigm proposed by the theory of stochastic
      resonances. We demonstrate that the random switching of a hydrogen (H(2))
      molecule can drive the oscillation of a macroscopic mechanical resonator. The
      H(2) motion was activated by tunneling electrons and caused fluctuations of the
      forces sensed by the tip of a noncontact atomic force microscope. The stochastic
      molecular noise and the periodic oscillation of the tip were coupled in a
      concerted dynamic that drives the system into self-oscillation. This phenomenon
      could be a way for enhancing the transfer of energy from incoherent sources into
      coherent dynamics of a molecular engine.

PMID- 23139329
TI  - Discovery of an organic trefoil knot.
AB  - Molecular knots remain difficult to produce using the current synthetic methods
      of chemistry because of their topological complexity. We report here the near
      quantitative self-assembly of a trefoil knot from a naphthalenediimide-based
      aqueous disulfide dynamic combinatorial library. The formation of the knot
      appears to be driven by the hydrophobic effect and leads to a structure in which
      the aromatic components are buried while the hydrophilic carboxylate groups
      remain exposed to the solvent. Moreover, the building block chirality constrains
      the topological conformation of the knot and results in its stereoselective
      synthesis. This work demonstrates that the hydrophobic effect provides a powerful
      strategy to direct the synthesis of entwined architectures.

PMID- 23139330
TI  - Development and disintegration of Maya political systems in response to climate
      change.
AB  - The role of climate change in the development and demise of Classic Maya
      civilization (300 to 1000 C.E.) remains controversial because of the absence of
      well-dated climate and archaeological sequences. We present a precisely dated
      subannual climate record for the past 2000 years from Yok Balum Cave, Belize.
      From comparison of this record with historical events compiled from well-dated
      stone monuments, we propose that anomalously high rainfall favored unprecedented
      population expansion and the proliferation of political centers between 440 and
      660 C.E. This was followed by a drying trend between 660 and 1000 C.E. that
      triggered the balkanization of polities, increased warfare, and the asynchronous
      disintegration of polities, followed by population collapse in the context of an
      extended drought between 1020 and 1100 C.E.

PMID- 23139331
TI  - A less cloudy future: the role of subtropical subsidence in climate sensitivity.
AB  - An observable constraint on climate sensitivity, based on variations in mid
      tropospheric relative humidity (RH) and their impact on clouds, is proposed. We
      show that the tropics and subtropics are linked by teleconnections that induce
      seasonal RH variations that relate strongly to albedo (via clouds), and that this
      covariability is mimicked in a warming climate. A present-day analog for future
      trends is thus identified whereby the intensity of subtropical dry zones in
      models associated with the boreal monsoon is strongly linked to projected cloud
      trends, reflected solar radiation, and model sensitivity. Many models,
      particularly those with low climate sensitivity, fail to adequately resolve these
      teleconnections and hence are identifiably biased. Improving model fidelity in
      matching observed variations provides a viable path forward for better predicting
      future climate.

PMID- 23139332
TI  - Bateman in nature: predation on offspring reduces the potential for sexual
      selection.
AB  - Sexual selection is driven by competition for mates, and the advantage of a
      competitor is determined by the number of offspring it produces. Early
      experiments by Angus Bateman characterized this interaction, and the quantitative
      relationship between a male's number of mates and number of offspring is known as
      the Bateman slope. Sexual dimorphism, one of the most obvious results of sexual
      selection, largely requires a positive Bateman relationship, and the slope
      provides an estimate of the potential for sexual selection. However, natural
      selection from the environment can also influence male success, as can random
      effects, and some have argued for inclusion of the latter in calculations of mate
      success. Data from pronghorn (Antilocapra americana) reveal the presence of a
      positive Bateman slope in each year of a 10-year study. We found no evidence that
      random effects skewed male mating success; however, substantial yearly variation
      in the Bateman slope due to predation on fawns was evident. These results support
      the validity of the Bateman relationship, yet they also demonstrate that
      environmental or extrinsic influences can limit the potential for sexual
      selection.

PMID- 23139333
TI  - Corals chemically cue mutualistic fishes to remove competing seaweeds.
AB  - Corals in the genus Acropora generate much of the structural complexity upon
      which coral reefs depend, but they are susceptible to damage from toxic seaweeds.
      Acropora nasuta minimizes this damage by chemically cuing symbiotic goby fishes
      (Gobiodon histrio or Paragobiodon echinocephalus) to remove the toxic seaweed
      Chlorodesmis fastigiata. Within minutes of seaweed contact, or contact from only
      seaweed chemical extract, the coral releases an odor that recruits gobies to trim
      the seaweed and dramatically reduce coral damage that would otherwise occur. In
      turn, chemically defended gobies become more toxic after consumption of this
      noxious alga. Mutualistic gobies and corals appear to represent a marine parallel
      to terrestrial ant-plants, in that the host provides shelter and food in return
      for protection from natural enemies.

PMID- 23139334
TI  - A core metabolic enzyme mediates resistance to phosphine gas.
AB  - Phosphine is a small redox-active gas that is used to protect global grain
      reserves, which are threatened by the emergence of phosphine resistance in pest
      insects. We find that polymorphisms responsible for genetic resistance cluster
      around the redox-active catalytic disulfide or the dimerization interface of
      dihydrolipoamide dehydrogenase (DLD) in insects (Rhyzopertha dominica and
      Tribolium castaneum) and nematodes (Caenorhabditis elegans). DLD is a core
      metabolic enzyme representing a new class of resistance factor for a redox-active
      metabolic toxin. It participates in four key steps of core metabolism, and
      metabolite profiles indicate that phosphine exposure in mutant and wild-type
      animals affects these steps differently. Mutation of DLD in C. elegans increases
      arsenite sensitivity. This specific vulnerability may be exploited to control
      phosphine-resistant insects and safeguard food security.

PMID- 23139335
TI  - Optical control of protein activity by fluorescent protein domains.
AB  - Fluorescent proteins (FPs) are widely used as optical sensors, whereas other
      light-absorbing domains have been used for optical control of protein
      localization or activity. Here, we describe light-dependent dissociation and
      association in a mutant of the photochromic FP Dronpa, and we used it to control
      protein activities with light. We created a fluorescent light-inducible protein
      design in which Dronpa domains are fused to both termini of an enzyme domain. In
      the dark, the Dronpa domains associate and cage the protein, but light induces
      Dronpa dissociation and activates the protein. This method enabled optical
      control over guanine nucleotide exchange factor and protease domains without
      extensive screening. Our findings extend the applications of FPs from exclusively
      sensing functions to also encompass optogenetic control.

PMID- 23139336
TI  - Mitochondrial network size scaling in budding yeast.
AB  - Mitochondria must grow with the growing cell to ensure proper cellular physiology
      and inheritance upon division. We measured the physical size of mitochondrial
      networks in budding yeast and found that mitochondrial network size increased
      with increasing cell size and that this scaling relation occurred primarily in
      the bud. The mitochondria-to-cell size ratio continually decreased in aging
      mothers over successive generations. However, regardless of the mother's age or
      mitochondrial content, all buds attained the same average ratio. Thus, yeast
      populations achieve a stable scaling relation between mitochondrial content and
      cell size despite asymmetry in inheritance.

PMID- 23139337
TI  - The associations between smoking and occupational categories: the Korea National
      Health and Nutrition Examination Survey from 2008 to 2010.
AB  - The implementation of smoke-free policies for workplaces and their impacts have
      been far from satisfactory. We investigated smoking prevalence in various
      occupations using data (n = 9283) from the Korea National Health and Nutrition
      Examination Survey collected from 2008 to 2010. Young adults who were working in
      the occupation categories of "service and sales," "skilled agricultural, fishery,
      and forest workers," and "crafts and machine operation" for men and "service and
      sales" for women showed 1.8 to 7.1 and 3.7 times higher (P < .05) smoking
      prevalence compared with the reference (managers and professionals),
      respectively, and the highest prevalence among the 7 occupational categories that
      were studied. Drinking and stress level were positively associated with being
      current smokers. We provide quantitative evidence supporting clinicians and
      policy makers wishing to establish smoking-cessation programs in workplaces for
      young adults in South Korea, and evidence supporting the improvement of
      prevention by the concomitant reduction of risk factors. 

PMID- 23139338
TI  - The international migration of health care professionals.
AB  - OBJECTIVES: The international migration of health care professionals has been
      recognized as a public health concern. A series of 'push' and 'pull' factors have
      been identified as driving forces for migration of doctors. The USA, UK, Canada
      and Australia are the main beneficiaries of medical migration, which has adverse
      consequences for health care systems in developing countries. Recently, a Global
      Code of Practice on the International Recruitment of Health Personnel was adopted
      by the World Health Assembly. In this paper, a summary of the most important
      recommendations of the Code is presented. In addition, the case of overseas
      trained psychiatrists in Australia is illustrated. These specialists complain of
      discriminatory practices due to the lack of recognition of their professional
      credentials. Research evidence from different countries confirms that
      international medical graduates face discriminatory obstacles to exercise their
      rights and practise their professions in developed countries. CONCLUSIONS: An
      international strategy is required to promote sustainable health care systems
      worldwide. Additional academic and scientific partnerships must be established
      between developed and developing nations in order to minimize discrepancies.
      There is an urgent need to review policies related to the recognition of medical
      credentials in host countries, including Australia. There are clear implications
      for psychiatry and psychiatrists.

PMID- 23139339
TI  - Osteopathic manipulative treatment: much more than simply a "hands-on"
      phenomenon.

PMID- 23139340
TI  - Oral histories: get them live!

PMID- 23139341
TI  - Management of primary knee osteoarthritis and indications for total knee
      arthroplasty for general practitioners.
AB  - Osteoarthritis (OA) of the knee, one of the most common causes of disability,
      continues to increase in prevalence as the older adult and obese populations
      grow. Often, the general practitioner is the first to evaluate a patient with a
      painful knee that has arthritis. Evidence-based evaluation and treatment
      guidelines recommend the use of nonoperative treatments before surgical treatment
      options such as total knee arthroplasty (TKA) are considered. Understanding
      available nonoperative treatment options is critical for physicians who first
      encounter patients with OA of the knee. The authors provide an overview of
      nonoperative treatment options for patients with OA, including weight loss,
      aerobic exercise, osteopathic manipulative treatment, nonsteroidal anti
      inflammatory drugs, and corticosteroid injections. The authors also discuss
      operative treatment options to be considered before TKA and review indications
      for TKA when other treatment options have been exhausted.

PMID- 23139342
TI  - Bibliometric measures and National Institutes of Health funding at colleges of
      osteopathic medicine, 2006-2010.
AB  - CONTEXT: During the past 20 years, colleges of osteopathic medicine (COMs) have
      made several advances in research that have substantially improved the
      osteopathic medical profession and the health of the US population. Furthering
      the understanding of research at COMs, particularly the factors influencing the
      attainment of extramural funds, is highly warranted and coincides with the
      missions of most COMs and national osteopathic organizations. OBJECTIVES: To
      describe bibliometric measures (numbers of peer-reviewed publications [ie,
      published articles] and citations of these publications, impact indices) at COMs
      from 2006 through 2010 and to examine statistical associations between these
      measures and the amount of National Institutes of Health (NIH) research funds
      awarded to COMs in 2006 and 2010. METHODS: A customized, systematic search of the
      Web of Science database was used to obtain bibliometric measures for 28 COMs. For
      the analyses, the bibliometric measures were summed or averaged over a 5-year
      period (2006 through 2010). The NIH database was used to obtain the amount of NIH
      funds for research grants and contracts received by the 28 COMs. Bivariate and
      multivariate statistical procedures were used to explore relationships between
      bibliometric measures and NIH funding amounts. RESULTS: The COMs with 2010 NIH
      funding, compared with COMs without NIH funding, had greater numbers of
      publications and citations and higher yearly average impact indices. Funding from
      the NIH in 2006 and 2010 was positively and significantly correlated with the
      numbers of publications, citations, and citations per publication and impact
      indices. The regression analysis indicated that 63.2% and 38.5% of the total
      variance in 2010 NIH funding explained by the model (adjusted R(2)=0.74) was
      accounted for by 2006 NIH funding and the combined bibliometric (ie, publications
      plus citations), respectively. CONCLUSION: Greater scholarly output leads to the
      procurement of more NIH funds for research at COMs.

PMID- 23139343
TI  - Self-reported physical health, mental health, and comorbid diseases among women
      with irritable bowel syndrome, fibromyalgia, or both compared with healthy
      control respondents.
AB  - CONTEXT: Physicians often encounter patients with functional pain disorders such
      as irritable bowel syndrome (IBS), fibromyalgia (FM), and their co-occurrence.
      Although these diseases are diagnosed exclusively by patients' report of
      symptoms, there are few comparative studies about patients' perceptions of these
      diseases. OBJECTIVE: To compare perceptions of these conditions among 4 groups-3
      clinical groups of older women with IBS, FM, or both disorders (IBS plus FM) and
      1 similarly aged control group of women with no IBS or FM-using their responses
      to survey questions about stressful life events, general physical and mental
      health, and general medical, pain, and psychiatric comorbidities. METHOD: Using
      data from the Biopsychosocial Religion and Health Study survey, responses from
      women were compared regarding a number of variables. To compare stress-related
      and physical-mental health profiles across the 4 groups, 1-way analyses of
      variance and chi(2) tests (with Tukey-Kramer and Tukey post hoc tests,
      respectively) were used, with alpha set to .05. RESULTS: The present study
      comprised 3811 women. Participants in the control group, the IBS group, the FM
      group, and the IBS plus FM group numbered 3213 (84.3%), 366 (9.6%), 161 (4.2%),
      and 71 (1.9%), respectively, with a mean (standard deviation) age of 62.4 (13.6),
      64.9 (13.7), 63.2 (10.8), and 61.1 (10.9) years, respectively. In general,
      participants in the control group reported fewer lifetime traumatic and major
      life stressors, better physical and mental health, and fewer comorbidities than
      respondents in the 3 clinical groups, and these differences were both
      statistically significant and substantial. Respondents with IBS reported fewer
      traumatic and major life stressors and better health (ratings and comorbidity
      data) than respondents with FM or respondents with IBS plus FM. Overall,
      respondents with both diseases reported the worst stressors and physical-mental
      health profiles and reported more diagnosed medical, pain, and psychiatric
      comorbidities. CONCLUSION: The results revealed statistically significant,
      relatively large differences in perceptions of quality of life measures and
      health profiles among the respondents in the control group and the 3 clinical
      groups.

PMID- 23139344
TI  - Still relevant: the profession's characteristics of yesterday and today.

PMID- 23139345
TI  - A novel approach to the diagnosis of stress-induced cardiomyopathy.
AB  - Stress-induced cardiomyopathy is becoming a more commonly recognized diagnosis,
      accounting for 2% to 3% of patients presenting with signs and symptoms of acute
      anterior myocardial infarction. We present the case of a 68-year-old man with
      dyspnea 9 days after an unrelated operation. After hospital admission, he
      complained of chest pain, and an electrocardiogram demonstrated ST-segment
      elevation in the anterolateral and inferior leads, ST-segment depression in lead
      aVR, and an absence of ST-segment changes in lead V(1). Cardiac biomarker levels
      were elevated. Transthoracic echocardiography demonstrated a left ventricular
      ejection fraction of 30% to 40%, basilar hyperactivity, apical dyskinesia, and
      distal inferior and anterior akinesia. Cardiac catheterization did not reveal any
      culprit obstructive lesion. He received a diagnosis of stress-induced
      cardiomyopathy and was treated according to established recommendations for
      systolic heart failure. His cardiac biomarkers returned to normal, and a repeated
      transthoracic echocardiogram 3 days later revealed nearly complete resolution of
      myocardial wall-motion abnormalities.

PMID- 23139346
TI  - Erythema migrans in early disseminated lyme disease.

PMID- 23139347
TI  - Practicing medicine is about more than standing on your own 2 feet.

PMID- 23139348
TI  - The peri-islet basement membrane, a barrier to infiltrating leukocytes in type 1
      diabetes in mouse and human.
AB  - We provide the first comprehensive analysis of the extracellular matrix (ECM)
      composition of peri-islet capsules, composed of the peri-islet basement membrane
      (BM) and subjacent interstitial matrix (IM), in development of type 1 diabetes in
      NOD mice and in human type 1 diabetes. Our data demonstrate global loss of peri
      islet BM and IM components only at sites of leukocyte infiltration into the
      islet. Stereological analyses reveal a correlation between incidence of insulitis
      and the number of islets showing loss of peri-islet BM versus islets with intact
      BMs, suggesting that leukocyte penetration of the peri-islet BM is a critical
      step. Protease- and protease inhibitor-specific microarray analyses (CLIP-CHIP)
      of laser-dissected leukocyte infiltrated and noninfiltrated pancreatic islets and
      confirmatory quantitative real time PCR and protein analyses identified cathepsin
      S, W, and C activity at sites of leukocyte penetration of the peri-islet BM in
      association with a macrophage subpopulation in NOD mice and human type 1 diabetic
      samples and, hence, potentially a novel therapeutic target specifically acting at
      the islet penetration stage. Interestingly, the peri-islet BM and underlying IM
      are reconstituted once inflammation subsides, indicating that the peri-islet BM
      producing cells are not lost due to the inflammation, which has important
      ramifications to islet transplantation studies.

PMID- 23139349
TI  - White matter microstructural integrity in youth with type 1 diabetes.
AB  - Decreased white and gray matter volumes have been reported in youth with type 1
      diabetes mellitus (T1DM), but the effects of hyperglycemia on white matter
      integrity have not been quantitatively assessed during brain development. We
      performed diffusion tensor imaging, using two complimentary approaches--region-of
      interest and voxelwise tract-based spatial statistics--to quantify white matter
      integrity in a large retrospective study of T1DM youth and control participants.
      Exposure to chronic hyperglycemia, severe hyperglycemic episodes, and severe
      hypoglycemia, as defined in the Diabetes Control and Complications Trial (DCCT),
      were estimated through medical records review, HbA(1c) levels, and interview of
      parents and youth. We found lower fractional anisotropy in the superior parietal
      lobule and reduced mean diffusivity in the thalamus in the T1DM group. A history
      of three or more severe hyperglycemic episodes was associated with reduced
      anisotropy and increased diffusivity in the superior parietal lobule and
      increased diffusivity in the hippocampus. These results add microstructural
      integrity of white matter to the range of structural brain alterations seen in
      T1DM youth and suggest vulnerability of the superior parietal lobule,
      hippocampus, and thalamus to glycemic extremes during brain development.
      Longitudinal analyses will be necessary to determine how these alterations change
      with age or additional glycemic exposure.

PMID- 23139350
TI  - Inhibition of carnitine palmitoyltransferase-1 activity alleviates insulin
      resistance in diet-induced obese mice.
AB  - Impaired skeletal muscle fatty acid oxidation has been suggested to contribute to
      insulin resistance and glucose intolerance. However, increasing muscle fatty acid
      oxidation may cause a reciprocal decrease in glucose oxidation, which might
      impair insulin sensitivity and glucose tolerance. We therefore investigated what
      effect inhibition of mitochondrial fatty acid uptake has on whole-body glucose
      tolerance and insulin sensitivity in obese insulin-resistant mice. C57BL/6 mice
      were fed a high-fat diet (60% calories from fat) for 12 weeks to develop insulin
      resistance. Subsequent treatment of mice for 4 weeks with the carnitine
      palmitoyltransferase-1 inhibitor, oxfenicine (150 mg/kg i.p. daily), resulted in
      improved whole-body glucose tolerance and insulin sensitivity. Exercise capacity
      was increased in oxfenicine-treated mice, which was accompanied by an increased
      respiratory exchange ratio. In the gastrocnemius muscle, oxfenicine increased
      pyruvate dehydrogenase activity, membrane GLUT4 content, and insulin-stimulated
      Akt phosphorylation. Intramyocellular levels of lipid intermediates, including
      ceramide, long-chain acyl CoA, and diacylglycerol, were also decreased. Our
      results demonstrate that inhibition of mitochondrial fatty acid uptake improves
      insulin sensitivity in diet-induced obese mice. This is associated with increased
      carbohydrate utilization and improved insulin signaling in the skeletal muscle,
      suggestive of an operating Randle Cycle in muscle.

PMID- 23139351
TI  - The neuropathic diabetic foot ulcer microbiome is associated with clinical
      factors.
AB  - Nonhealing diabetic foot ulcers (DFUs) are a common and costly complication of
      diabetes. Microbial burden, or "bioburden," is believed to underlie delayed
      healing, although little is known of those clinical factors that may influence
      microbial load, diversity, and/or pathogenicity. We profiled the microbiomes of
      neuropathic nonischemic DFUs without clinical evidence of infection in 52
      individuals using high-throughput sequencing of the bacterial 16S ribosomal RNA
      gene. Comparatively, wound cultures, the standard diagnostic in the clinic,
      vastly underrepresent microbial load, microbial diversity, and the presence of
      potential pathogens. DFU microbiomes were heterogeneous, even in our tightly
      restricted study population, but partitioned into three clusters distinguished
      primarily by dominant bacteria and diversity. Ulcer depth was associated with
      ulcer cluster, positively correlated with abundance of anaerobic bacteria, and
      negatively correlated with abundance of Staphylococcus. Ulcer duration was
      positively correlated with bacterial diversity, species richness, and relative
      abundance of Proteobacteria, but was negatively correlated with relative
      abundance of Staphylococcus. Finally, poor glycemic control was associated with
      ulcer cluster, with poorest median glycemic control concentrating to
      Staphylococcus-rich and Streptococcus-rich ulcer clusters. Analyses of microbial
      community membership and structure may provide the most useful metrics in
      prospective studies to delineate problematic bioburden from benign colonization
      that can then be used to drive clinical treatment.

PMID- 23139352
TI  - Ceramides contained in LDL are elevated in type 2 diabetes and promote
      inflammation and skeletal muscle insulin resistance.
AB  - Dysregulated lipid metabolism and inflammation are linked to the development of
      insulin resistance in obesity, and the intracellular accumulation of the
      sphingolipid ceramide has been implicated in these processes. Here, we explored
      the role of circulating ceramide on the pathogenesis of insulin resistance.
      Ceramide transported in LDL is elevated in the plasma of obese patients with type
      2 diabetes and correlated with insulin resistance but not with the degree of
      obesity. Treating cultured myotubes with LDL containing ceramide promoted
      ceramide accrual in cells and was accompanied by reduced insulin-stimulated
      glucose uptake, Akt phosphorylation, and GLUT4 translocation compared with LDL
      deficient in ceramide. LDL-ceramide induced a proinflammatory response in
      cultured macrophages via toll-like receptor-dependent and -independent
      mechanisms. Finally, infusing LDL-ceramide into lean mice reduced insulin
      stimulated glucose uptake, and this was due to impaired insulin action
      specifically in skeletal muscle. These newly identified roles of LDL-ceramide
      suggest that strategies aimed at reducing hepatic ceramide production or reducing
      ceramide packaging into lipoproteins may improve skeletal muscle insulin action.

PMID- 23139353
TI  - Neuronal androgen receptor regulates insulin sensitivity via suppression of
      hypothalamic NF-kappaB-mediated PTP1B expression.
AB  - Clinical investigations highlight the increased incidence of metabolic syndrome
      in prostate cancer (PCa) patients receiving androgen deprivation therapy (ADT).
      Studies using global androgen receptor (AR) knockout mice demonstrate that AR
      deficiency results in the development of insulin resistance in males. However,
      mechanisms by which AR in individual organs coordinately regulates insulin
      sensitivity remain unexplored. Here we tested the hypothesis that functional AR
      in the brain contributes to whole-body insulin sensitivity regulation and to the
      metabolic abnormalities developed in AR-deficient male mice. The mouse model
      selectively lacking AR in the central nervous system and AR-expressing GT1-7
      neuronal cells were established and used to delineate molecular mechanisms in
      insulin signaling modulated by AR. Neuronal AR deficiency leads to reduced
      insulin sensitivity in middle-aged mice. Neuronal AR regulates hypothalamic
      insulin signaling by repressing nuclear factor-kappaB (NF-kappaB)-mediated
      induction of protein-tyrosine phosphatase 1B (PTP1B). Hypothalamic insulin
      resistance leads to hepatic insulin resistance, lipid accumulation, and visceral
      obesity. The functional deficiency of AR in the hypothalamus leads to male mice
      being more susceptible to the effects of high-fat diet consumption on PTP1B
      expression and NF-kappaB activation. These findings suggest that in men with PCa
      undergoing ADT, reduction of AR function in the brain may contribute to insulin
      resistance and visceral obesity. Pharmacotherapies targeting neuronal AR and NF
      kappaB may be developed to combat the metabolic syndrome in men receiving ADT and
      in elderly men with age-associated hypogonadism.

PMID- 23139354
TI  - Identification of cross-species shared transcriptional networks of diabetic
      nephropathy in human and mouse glomeruli.
AB  - Murine models are valuable instruments in defining the pathogenesis of diabetic
      nephropathy (DN), but they only partially recapitulate disease manifestations of
      human DN, limiting their utility. To define the molecular similarities and
      differences between human and murine DN, we performed a cross-species comparison
      of glomerular transcriptional networks. Glomerular gene expression was profiled
      in patients with early type 2 DN and in three mouse models (streptozotocin DBA/2,
      C57BLKS db/db, and eNOS-deficient C57BLKS db/db mice). Species-specific
      transcriptional networks were generated and compared with a novel network
      matching algorithm. Three shared human-mouse cross-species glomerular
      transcriptional networks containing 143 (Human-DBA STZ), 97 (Human-BKS db/db),
      and 162 (Human-BKS eNOS(-/-) db/db) gene nodes were generated. Shared nodes
      across all networks reflected established pathogenic mechanisms of diabetes
      complications, such as elements of Janus kinase (JAK)/signal transducer and
      activator of transcription (STAT) and vascular endothelial growth factor receptor
      (VEGFR) signaling pathways. In addition, novel pathways not previously associated
      with DN and cross-species gene nodes and pathways unique to each of the human
      mouse networks were discovered. The human-mouse shared glomerular transcriptional
      networks will assist DN researchers in selecting mouse models most relevant to
      the human disease process of interest. Moreover, they will allow identification
      of new pathways shared between mice and humans.

PMID- 23139355
TI  - Metabolite profiling reveals normal metabolic control in carriers of mutations in
      the glucokinase gene (MODY2).
AB  - Mutations in the gene encoding glucokinase (GCK) cause a mild hereditary form of
      diabetes termed maturity-onset diabetes of the young (MODY)2 or GCK-MODY. The
      disease does not progress over time, and diabetes complications rarely develop.
      It has therefore been suggested that GCK-MODY represents a metabolically
      compensated condition, but experimental support for this notion is lacking. Here,
      we profiled metabolites in serum from patients with MODY1 (HNF4A), MODY2 (GCK),
      MODY3 (HNF1A), and type 2 diabetes and from healthy individuals to characterize
      metabolic perturbations caused by specific mutations. Analysis of four GCK-MODY
      patients revealed a metabolite pattern similar to that of healthy individuals,
      while other forms of diabetes differed markedly in their metabolite profiles.
      Furthermore, despite elevated glucose concentrations, carriers of GCK mutations
      showed lower levels of free fatty acids and triglycerides than healthy control
      subjects. The metabolite profiling was confirmed by enzymatic assays and
      replicated in a cohort of 11 GCK-MODY patients. Elevated levels of fatty acids
      are known to associate with beta-cell dysfunction, insulin resistance, and
      increased incidence of late complications. Our results show that GCK-MODY
      represents a metabolically normal condition, which may contribute to the lack of
      late complications and the nonprogressive nature of the disease.

PMID- 23139356
TI  - Intrahypothalamic estradiol regulates glucose metabolism via the sympathetic
      nervous system in female rats.
AB  - Long-term reduced hypothalamic estrogen signaling leads to increased food intake
      and decreased locomotor activity and energy expenditure, and ultimately results
      in obesity and insulin resistance. In the current study, we aimed to determine
      the acute obesity-independent effects of hypothalamic estrogen signaling on
      glucose metabolism. We studied endogenous glucose production (EGP) and insulin
      sensitivity during selective modulation of systemic or intrahypothalamic
      estradiol (E2) signaling in rats 1 week after ovariectomy (OVX). OVX caused a 17%
      decrease in plasma glucose, which was completely restored by systemic E2.
      Likewise, the administration of E2 by microdialysis, either in the hypothalamic
      paraventricular nucleus (PVN) or in the ventromedial nucleus (VMH), restored
      plasma glucose. The infusion of an E2 antagonist via reverse microdialysis into
      the PVN or VMH attenuated the effect of systemic E2 on plasma glucose.
      Furthermore, E2 administration in the VMH, but not in the PVN, increased EGP and
      induced hepatic insulin resistance. E2 administration in both the PVN and the VMH
      resulted in peripheral insulin resistance. Finally, sympathetic, but not
      parasympathetic, hepatic denervation blunted the effect of E2 in the VMH on both
      EGP and hepatic insulin sensitivity. In conclusion, intrahypothalamic estrogen
      regulates peripheral and hepatic insulin sensitivity via sympathetic signaling to
      the liver.

PMID- 23139357
TI  - Insights into the molecular mechanism for type 2 diabetes susceptibility at the
      KCNQ1 locus from temporal changes in imprinting status in human islets.
AB  - The molecular basis of type 2 diabetes predisposition at most established
      susceptibility loci remains poorly understood. KCNQ1 maps within the 11p15.5
      imprinted domain, a region with an established role in congenital growth
      phenotypes. Variants intronic to KCNQ1 influence diabetes susceptibility when
      maternally inherited. By use of quantitative PCR and pyrosequencing of human
      adult islet and fetal pancreas samples, we investigated the imprinting status of
      regional transcripts and aimed to determine whether type 2 diabetes risk alleles
      influence regional DNA methylation and gene expression. The results demonstrate
      that gene expression patterns differ by developmental stage. CDKN1C showed
      monoallelic expression in both adult and fetal tissue, whereas PHLDA2, SLC22A18,
      and SLC22A18AS were biallelically expressed in both tissues. Temporal changes in
      imprinting were observed for KCNQ1 and KCNQ1OT1, with monoallelic expression in
      fetal tissues and biallelic expression in adult samples. Genotype at the type 2
      diabetes risk variant rs2237895 influenced methylation levels of regulatory
      sequence in fetal pancreas but without demonstrable effects on gene expression.
      We demonstrate that CDKN1C, KCNQ1, and KCNQ1OT1 are most likely to mediate
      diabetes susceptibility at the KCNQ1 locus and identify temporal differences in
      imprinting status and methylation effects, suggesting that diabetes risk effects
      may be mediated in early development.

PMID- 23139358
TI  - Rosuvastatin changes cytokine expressions in ischemic territory and preserves
      heart function after acute myocardial infarction in rats.
AB  - AIM: To investigate the mechanism of rosuvastatin in preserving cardiac function
      after acute myocardial infarction (AMI) in a rat model. METHODS: Sprague-Dawley
      rats were randomized to receive either rosuvastatin (5 mg/kg every day) or
      placebo (0.5% CMC-Na), respectively, by daily gavage from 7 days before AMI.
      Acute myocardial infarction (AMI) model was induced by left anterior descending
      coronary artery ligation through a lateral thoracotomy in rats. The expressions
      of stromal-cell-derived factor 1 (SDF-1), chemokine motif CXC receptor 4 (CXCR
      4), vascular endothelial growth factor (VEGF), and intercellular adhesion
      molecule 1 (ICAM-1) in peri-infarction region and nonischemic region at different
      time points were determined by the Western blot analysis. Immunohistochemistry
      analysis was performed on the 28th day after AMI to investigate the accumulation
      of CD90+, CD133+, and c-kit+ progenitor cells in the peri-infarction region.
      Masson staining and echocardiograph were performed to evaluate the left
      ventricular remodeling and postinfarction cardiac function 4 weeks after AMI.
      RESULTS: Western blot analysis showed that rosuvastatin could change the cytokine
      expressions in the peri-infarction region by upregulating the SDF-1 expression
      and downregulating the expressions of CXCR-4, ICAM-1, and VEGF in 4 to 14 days
      after AMI. Immunohistochemistry analysis showed that rosuvastatin treatment was
      associated with increased accumulation of CD90+, CD133+, and c-kit+ progenitor
      cells in the peri-infarction region. Masson staining and echocardiograph
      confirmed that rosuvastatin could attenuate left ventricular remodeling and
      improve postinfarction systolic function. CONCLUSION: The data suggest that
      rosuvastatin can protect the heart from ischemic injury and preserve the cardiac
      function in rats in vivo. The changing expressions of SDF-1, CXCR-4, ICAM-1, and
      VEGF, and the accumulation of progenitor cells were involved in this process.

PMID- 23139359
TI  - Intensive-dose atorvastatin regimen halts progression of atherosclerotic plaques
      in new-onset unstable angina with borderline vulnerable plaque lesions.
AB  - To compare the therapeutic effects of intensive versus moderate dosage of
      atorvastatin regimens in new-onset unstable angina with borderline lesions, 100
      patients were randomized to receive either 80 mg/d or 20 mg/d atorvastatin for 9
      months. Clinical symptoms, lipid profiles, and coronary stenosis (evaluated by
      coronary angiography and intravascular ultrasound) were compared to their
      corresponding baselines within each group and between the 2 groups after 9 months
      of treatment. The results showed that (1) when compared to their corresponding
      baselines, both groups exhibited improvement in clinical symptoms, a significant
      decrease in total cholesterol, triglyceride, low-density lipoprotein cholesterol
      (LDL-C), and high-sensitivity C-reactive protein (hs-CRP; P < .01) and a
      significant increase in high-density lipoprotein cholesterol (HDL-C); (2) the
      improvement in clinical symptoms and the decrease in LDL-C and hs-CRP were
      significantly greater (P < .01) in the intensive-dose group than in the moderate
      dose group; (3) the mean plaque volume did not progress in the intensive-dose
      group but increased significantly (P < .05) in the moderate-dose group. We
      conclude that compared to the moderate dose, the intensive-dose regimen
      significantly improves clinical symptoms, lowers LDL-C and hs-CRP, and halts the
      progression of borderline atherosclerotic plaques in patients with new-onset
      unstable angina.

PMID- 23139360
TI  - The relationship between the prescription of psychotropic drugs and suicide rates
      in older people in England and Wales.
AB  - BACKGROUND: Several studies have reported an inverse correlation between general
      population and elderly suicide rates and antidepressant prescribing rates.
      Correlations between general population and elderly suicide rates and prescribing
      rates of other psychotropic drugs have also been reported. All studies of elderly
      suicide rates have used data over a decade old. METHODS: The relationship between
      elderly suicide rates and prescription rates of psychotropic drugs by the broad
      British National Formulary (BNF) categories, for individual psychotropic drug
      groups within the BNF categories (e.g. SSRIs), and for individual psychotropic
      drugs was examined over a 12-year period (1995-2006) using Spearman's rank
      correlation. All data were ascertained from the archives of the National
      Statistics Office. RESULTS: There was an absence of significant correlations
      between elderly suicides rates and rates of prescriptions of psychotropic drugs
      in the broad BNF categories, individual psychotropic drug groups and individual
      psychotropic drugs. DISCUSSION: The findings may be due to methodological flaws.
      However, if they are genuine, then the following approaches require consideration
      to further reduce suicide rates: (1) development of strategies to ensure
      continued prescription of psychotropic drugs at the current level; (2)
      development of strategies to improve non-pharmacological measures, including
      improved mental health services provision for older people, improved assessment
      of suicide risk, increased availability of psychosocial interventions and
      restricting the availability of methods of suicide; and (3) development of
      strategies to implement improvement in distal risk (e.g. societal socio-economic
      status) and protective (e.g. societal educational attainment) factors for suicide
      at a societal level.

PMID- 23139362
TI  - Automated image analysis of skeletal muscle fiber cross-sectional area.
AB  - Morphological characteristics of muscle fibers, such as fiber size, are critical
      factors that determine the health and function of the muscle. However, at this
      time, quantification of muscle fiber cross-sectional area is still a manual or,
      at best, a semiautomated process. This process is labor intensive, time
      consuming, and prone to errors, leading to high interobserver variability. We
      have developed and validated an automatic image segmentation algorithm and
      compared it directly with commercially available semiautomatic software currently
      considered state of the art. The proposed automatic segmentation algorithm was
      evaluated against a semiautomatic method with manual annotation using 35 randomly
      selected cross-sectional muscle histochemical images. The proposed algorithm
      begins with ridge detection to enhance the muscle fiber boundaries, followed by
      robust seed detection based on concave area identification to find initial seeds
      for muscle fibers. The final muscle fiber boundaries are automatically delineated
      using a gradient vector flow deformable model. Our automatic approach is accurate
      and represents a significant advancement in efficiency; quantification of fiber
      area in muscle cross sections was reduced from 25-40 min/image to 15 s/image,
      while accommodating common quantification obstacles including morphological
      variation (e.g., heterogeneity in fiber size and fibrosis) and technical
      artifacts (e.g., processing defects and poor staining quality). Automatic
      quantification of muscle fiber cross-sectional area using the proposed method is
      a powerful tool that will increase sensitivity, objectivity, and efficiency in
      measuring muscle adaptation.

PMID- 23139361
TI  - The impact of arousal state, sex, and sleep apnea on the magnitude of progressive
      augmentation and ventilatory long-term facilitation.
AB  - We examined the impact of arousal state, sex, and obstructive sleep apnea (OSA)
      on the magnitude of progressive augmentation of the hypoxic ventilatory response
      and ventilatory long-term facilitation (vLTF). We also examined whether exposure
      to intermittent hypoxia during sleep has an impact on the apnea-hypopnea index
      (AHI) in individuals with OSA. Ten men and seven women with OSA, along with ten
      healthy men and ten healthy women, were exposed to twelve 2-min episodes of
      hypoxia (end-tidal PO(2): 50 Torr) in the presence of sustained hypercapnia (end
      tidal PCO(2): 3 Torr above baseline), followed by a 30-min recovery period during
      wakefulness and sleep. The OSA participants completed an additional sham study
      during sleep. The AHI during the first hour of sleep following the intermittent
      hypoxia and sham protocols were compared. Progressive augmentation was only
      evident during wakefulness and was enhanced in the OSA participants. vLTF was
      evident during wakefulness and sleep. When standardized to baseline, vLTF was
      greater during wakefulness and was enhanced in the OSA group (men: wakefulness
      1.39 +/- 0.08 vs. sleep 1.14 +/- 0.03; women: wakefulness 1.35 +/- 0.03 vs. sleep
      1.16 +/- 0.05 fraction of baseline; P <= 0.001) compared with control (men:
      wakefulness 1.19 +/- 0.03 vs. sleep 1.09 +/- 0.03; women: wakefulness 1.26 +/-
      0.05 vs. sleep 1.08 +/- 0.04 fraction of baseline; P <= 0.001). The AHI following
      exposure to intermittent hypoxia was increased (intermittent hypoxia 72.8 +/- 7.3
      vs. sham 56.5 +/- 7.0 events/h; P <= 0.01). Sex-related differences were not
      observed for the primary measures. We conclude that progressive augmentation is
      not evident, and the magnitude of vLTF is diminished during sleep compared with
      wakefulness in men and women. However, when present, the phenomena are enhanced
      in individuals with OSA. The AHI data indicate that, under the prevailing
      experimental conditions, vLTF did not serve to mitigate apnea severity.

PMID- 23139363
TI  - Water drinking-related muscle contraction induces the pressor response via
      mechanoreceptors in conscious rats.
AB  - Water drinking is known to induce the pressor response. The efferent pathway in
      this response involves sympathoexcitation, because the pressor response was
      completely abolished by ganglionic blockade or an alpha(1)-adrenergic antagonist.
      However, the afferent pathway in this response has not been identified. In the
      present study, we hypothesized that water itself stimulates the upper digestive
      tract to induce the pressor response, and/or drinking-related muscle contraction
      induces the pressor response via mechanoreceptors. To examine this hypothesis, we
      evaluated the pressor response induced by spontaneous or passive water drinking
      in conscious rats. Since the baroreflex modulates and obscures the pressor
      response, the experiments were conducted using rats with sinoaortic denervation.
      The pressor response was not suppressed by 1) transient oral surface anesthesia
      using lidocaine, 2) bilateral denervation of the glossopharyngeal nerve and
      sensory branch of the superior laryngeal nerve, or 3) denervation of the tunica
      adventitia in the esophagus. However, the pressor response was significantly
      suppressed (by -52%) by intravenous gadolinium chloride administration.
      Electrical stimulation of the hypoglossal nerve induced the pressor response,
      which was significantly suppressed (by -57%) by intravenous gadolinium chloride
      administration and completely abolished by severing the distal end of this nerve.
      These results indicate that afferent signals from mechanoreceptors in drinking
      related muscles are involved in the water drinking-induced pressor response.

PMID- 23139364
TI  - Diallyl trisulfide and diallyl disulfide ameliorate cardiac dysfunction by
      suppressing apoptotic and enhancing survival pathways in experimental diabetic
      rats.
AB  - Cardiovascular disease is one of the major causes of mortality in diabetic
      patients. Mounting studies have shown that garlic exhibits, possibly through its
      antioxidant potential, diverse biological activities. In this study, we
      investigated the alleviating effects of garlic oil (GO) and its two major
      components, diallyl disulfide (DADS) and diallyl trisulfide (DATS), on diabetic
      cardiomyopathy in rats. Physiological cardiac parameters were obtained using
      echocardiography. Apoptotic cells were evaluated using TUNEL and DAPI staining.
      Protein expression levels were determined using Western blotting analysis. Our
      findings indicated that in diabetic rat hearts significantly decreased fractional
      shortening percentage, increased levels of nitrotyrosine, an elevated number of
      TUNEL-positive cells, enhanced levels of caspase 3 expression, and decreased PI3K
      Akt signaling pathway activities were observed. Furthermore, all of these
      alterations were reversed following both GO and DATS (or DADS) administrations
      through increasing PI3K-Akt signaling pathway activities and inhibiting both the
      death receptor-dependent and the mitochondria-dependent apoptotic pathways. In
      conclusion, this study shows that DATS and DADS, with the efficacy order DATS >
      DADS, have the therapeutic potential for ameliorating diabetic cardiomyopathy.
      Furthermore, the therapeutic effects of GO on diabetic cardiomyopathy should be
      mainly from DATS and DADS.

PMID- 23139365
TI  - Cardiac baroreflex function and dynamic cerebral autoregulation in elderly
      Masters athletes.
AB  - Cerebral blood flow (CBF) is stably maintained through the combined effects of
      blood pressure (BP) regulation and cerebral autoregulation. Previous studies
      suggest that aerobic exercise training improves cardiac baroreflex function and
      beneficially affects BP regulation, but may negatively affect cerebral
      autoregulation. The purpose of this study was to reveal the impact of lifelong
      exercise on cardiac baroreflex function and dynamic cerebral autoregulation (CA)
      in older adults. Eleven Masters athletes (MA) (8 men, 3 women; mean age 73 +/- 6
      yr; aerobic training >15 yr) and 12 healthy sedentary elderly (SE) (7 men, 5
      women; mean age 71 +/- 6 yr) participated in this study. BP, CBF velocity (CBFV),
      and heart rate were measured during resting conditions and repeated sit-stand
      maneuvers to enhance BP variability. Baroreflex gain was assessed using transfer
      function analysis of spontaneous changes in systolic BP and R-R interval in the
      low frequency range (0.05-0.15 Hz). Dynamic CA was assessed during sit-stand
      induced changes in mean BP and CBFV at 0.05 Hz (10 s sit, 10 s stand). Cardiac
      baroreflex gain was more than doubled in MA compared with SE (MA, 7.69 +/- 7.95;
      SE, 3.18 +/- 1.29 ms/mmHg; P = 0.018). However, dynamic CA was similar in the two
      groups (normalized gain: MA, 1.50 +/- 0.56; SE, 1.56 +/- 0.42% CBFV/mmHg; P =
      0.792). These findings suggest that lifelong exercise improves cardiac baroreflex
      function, but does not alter dynamic CA. Thus, beneficial effects of exercise
      training on BP regulation can be achieved in older adults without compromising
      dynamic regulation of CBF.

PMID- 23139366
TI  - Vasculoprotective effect of U50,488H in rats exposed to chronic hypoxia: role of
      Akt-stimulated NO production.
AB  - Impairment of pulmonary endothelium function in the pulmonary artery is a direct
      result of chronic hypoxia. This study is to investigate the vasculoprotective
      effects of U50,488H (a selective kappa-opioid receptor agonist) and its
      underlying mechanism in hypoxia-induced pulmonary artery endothelial functional
      injury. Chronic hypoxia was simulated by exposing the rats to 10% oxygen for 2
      wk. After hypoxia, right ventricular pressure (RVP) and right ventricular
      hypertrophy index (RVHI) were measured. The pulmonary vascular dysfunction,
      effect of nitric oxide synthase inhibitor (l-NAME) on the relaxation of U50,488H,
      and level of nitric oxide (NO) were determined. In vitro, the signaling pathway
      involved in the anti-apoptotic effect of U50,488H was investigated. Cultured
      endothelial cells were subjected to simulated hypoxia, and cell apoptosis was
      determined by TUNEL staining. U50,488H (1.25 mg/kg) significantly reduced RVP and
      RVHI in hypoxia. U50,488H markedly improved both pulmonary endothelial function
      (maximal vasorelaxation in response to ACh: 74.9 +/- 1.8%, n = 6, P <0.01 vs.
      hypoxia for 2 wk group) and increased total NO production (1.65 fold). U50,488H
      relaxed the pulmonary artery rings of the hypoxic rats. This effect was partly
      abolished by l-NAME. In cells, U50,488H both increased NO production and reduced
      hypoxia-induced apoptosis. Moreover, pretreatment with nor-binaltorphimine (nor
      BNI, a selective kappa-opioid receptor antagonist), PI3K inhibitor, Akt inhibitor
      or l-NAME almost abolished anti-apoptotic effect exerted by U50,488H. U50,488H
      resulted in increases in Akt and eNOS phosphorylation. These results demonstrate
      that pretreatment with U50,488H attenuates hypoxia-induced pulmonary vascular
      endothelial dysfunction in an Akt-dependent and NO-mediated fashion.

PMID- 23139367
TI  - Modulation of the axon-reflex response to local heat by reactive oxygen species
      in subjects with chronic fatigue syndrome.
AB  - Local cutaneous heating causes vasodilation as an initial first peak, a nadir,
      and increase to plateau. Reactive oxygen species (ROS) modulate the heat plateau
      in healthy controls. The initial peak, due to C-fiber nociceptor-mediated axon
      reflexes, is blunted with local anesthetics and may serve as a surrogate for the
      cutaneous response to peripheral heat. Chronic fatigue syndrome (CFS) subjects
      report increased perception of pain. To determine the role of ROS in this
      neurally mediated response, we evaluated changes in cutaneous blood flow from
      local heat in nine CFS subjects (16-22 yr) compared with eight healthy controls
      (18-26 yr). We heated skin to 42 degrees C and measured local blood flow as a
      percentage of maximum cutaneous vascular conductance (%CVC(max)). Although CFS
      subjects had significantly lower baseline flow [8.75 +/- 0.56 vs. 12.27 +/- 1.07
      (%CVC(max), CFS vs. control)], there were no differences between groups to local
      heat. We then remeasured this with apocynin to inhibit NADPH oxidase, allopurinol
      to inhibit xanthine oxidase, tempol to inhibit superoxide, and ebselen to reduce
      H(2)O(2). Apocynin significantly increased baseline blood flow (before heat,
      14.91 +/- 2.21 vs. 8.75 +/- 1.66) and the first heat peak (69.33 +/- 3.36 vs.
      59.75 +/- 2.75). Allopurinol and ebselen only enhanced the first heat peaks
      (71.55 +/- 2.48 vs. 61.72 +/- 2.01 and 76.55 +/- 5.21 vs. 58.56 +/- 3.66,
      respectively). Tempol had no effect on local heating. None of these agents
      changed the response to local heat in control subjects. Thus the response to heat
      may be altered by local levels of ROS, particularly H(2)O(2) in CFS subjects, and
      may be related to their hyperesthesia/hyperalgesia.

PMID- 23139368
TI  - The magnitude of heat stress-induced reductions in cerebral perfusion does not
      predict heat stress-induced reductions in tolerance to a simulated hemorrhage.
AB  - The mechanisms responsible for heat stress-induced reductions in tolerance to a
      simulated hemorrhage are unclear. Although a high degree of variability exists in
      the level of reduction in tolerance amongst individuals, syncope will always
      occur when cerebral perfusion is inadequate. This study tested the hypothesis
      that the magnitude of reduction in cerebral perfusion during heat stress is
      related to the reduction in tolerance to a lower body negative pressure (LBNP)
      challenge. On different days (one during normothermia and the other after a 1.5
      degrees C rise in internal temperature), 20 individuals were exposed to a LBNP
      challenge to presyncope. Tolerance was quantified as a cumulative stress index,
      and the difference in cumulative stress index between thermal conditions was used
      to categorize individuals most (large difference) and least (small difference)
      affected by the heat stress. Cerebral perfusion, as indexed by middle cerebral
      artery blood velocity, was reduced during heat stress compared with normothermia
      (P < 0.001); however, the magnitude of reduction did not differ between groups (P
      = 0.51). In the initial stage of LBNP during heat stress (LBNP 20 mmHg), middle
      cerebral artery blood velocity and end-tidal PCO(2) were lower; whereas, heart
      rate was higher in the large difference group compared with small difference
      group (P < 0.05 for all). These data indicate that variability in heat stress
      induced reductions in tolerance to a simulated hemorrhage is not related to
      reductions in cerebral perfusion in this thermal condition. However, responses
      affecting cerebral perfusion during LBNP may explain the interindividual
      variability in tolerance to a simulated hemorrhage when heat stressed.

PMID- 23139369
TI  - I am 80 going on 18: exercise and the fountain of youth.

PMID- 23139370
TI  - ABC transporter genes and risk of type 2 diabetes: a study of 40,000 individuals
      from the general population.
AB  - OBJECTIVE: Alterations of pancreatic beta-cell cholesterol content may contribute
      to beta-cell dysfunction. Two important determinants of intracellular cholesterol
      content are the ATP-binding cassette (ABC) transporters A1 (ABCA1) and -G1
      (ABCG1). Whether genetic variation in ABCA1 and ABCG1 predicts risk of type 2
      diabetes in the general population is unknown. RESEARCH DESIGN AND METHODS: We
      tested whether genetic variation in the promoter and coding regions of ABCA1 and
      ABCG1 predicted risk of type 2 diabetes in the general population. Twenty-seven
      variants, identified by previous resequencing of both genes, were genotyped in
      the Copenhagen City Heart Study (CCHS) (n = 10,185). Two loss-of-function
      mutations (ABCA1 N1800H and ABCG1 g.-376C>T) (n = 322) and a common variant
      (ABCG1 g.-530A>G) were further genotyped in the Copenhagen General Population
      Study (CGPS) (n = 30,415). RESULTS: Only one of the variants examined, ABCG1 g.
      530A>G, predicted a decreased risk of type 2 diabetes in the CCHS (P for trend =
      0.05). Furthermore, when validated in the CGPS or in the CCHS and CGPS combined
      (n = 40,600), neither the two loss-of-function mutations (ABCA1 N1800H, ABCG1 g.
      376C>T) nor ABCG1 g.-530A>G were associated with type 2 diabetes (P values >0.57
      and >0.30, respectively). CONCLUSIONS: Genetic variations in ABCA1 and ABCG1 were
      not associated with increased risk of type 2 diabetes in the general population.
      These data were obtained in general population samples harboring the largest
      number of heterozygotes for loss-of-function mutations in ABCA1 and ABCG1.

PMID- 23139371
TI  - Right ventricular involvement in diabetic cardiomyopathy.
AB  - OBJECTIVE: To compare magnetic resonance imaging-derived right ventricular (RV)
      dimensions and function between men with type 2 diabetes and healthy subjects,
      and to relate these parameters to left ventricular (LV) dimensions and function.
      RESEARCH DESIGN AND METHODS: RV and LV volumes and functions were assessed in 78
      men with uncomplicated type 2 diabetes and 28 healthy men within the same range
      of age using magnetic resonance imaging. Steady-state free precession sequences
      were used to assess ventricular dimensions. Flow velocity mapping across the
      pulmonary valve and tricuspid valve was used to assess RV outflow and diastolic
      filling patterns, respectively. Univariate general linear models were used for
      statistical analyses. RESULTS: RV end-diastolic volume was significantly
      decreased in patients compared with healthy subjects after adjustment for BMI and
      pulse pressure (177 +/- 28 mL vs. 197 +/- 47 mL, P < 0.01). RV systolic function
      was impaired: peak ejection rate across the pulmonary valve was decreased (433 +/
      54 mL/s vs. 463 +/- 71 mL/s, P < 0.01) and pulmonary flow acceleration time was
      longer (124 +/- 17 ms vs. 115 +/- 25 ms, P < 0.05). Indexes of RV diastolic
      function were impaired: peak filling rate and peak deceleration gradient of the
      early filling phase were 315 +/- 63 mL/s vs. 356 +/- 90 mL/s (P < 0.01) and 2.3
      +/- 0.8 mL/s(2) * 10(-3) vs. 2.8 +/- 0.8 mL/s(2) * 10(-3) (P < 0.01),
      respectively. All RV parameters were strongly associated with its corresponding
      LV parameter (P < 0.001). CONCLUSIONS: Diabetic cardiomyopathy affects the right
      ventricle, as demonstrated by RV remodeling and impaired systolic and diastolic
      functions in men with type 2 diabetes, in a similar manner as changes in LV
      dimensions and functions. These observations suggest that RV impairment might be
      a component of the diabetic cardiomyopathy phenotype.

PMID- 23139372
TI  - Altered brain microstructure assessed by diffusion tensor imaging in patients
      with diabetes and gastrointestinal symptoms.
AB  - OBJECTIVE: In patients with long-standing diabetes mellitus (DM), there is
      increasing evidence for abnormal processing of gastrointestinal sensations in the
      central nervous system. Using magnetic resonance diffusion tensor imaging, we
      characterized brain microstructure in areas involved in visceral sensory
      processing and correlated these findings to clinical parameters. RESEARCH DESIGN
      AND METHODS: Twenty-six patients with DM and gastrointestinal symptoms and 23
      healthy control subjects were studied in a 3T scanner. The apparent diffusion
      coefficient (i.e., diffusivity of water) and fractional anisotropy (FA) (i.e.,
      organization of fibers) were assessed in the "sensory matrix" (cingulate cortex,
      insula, prefrontal and secondary sensory cortex, amygdala, and corona radiata)
      and in corpus callosum. RESULTS: Patients had decreased FA values compared with
      control subjects in 1) all areas (P = 0.025); 2) anterior (P < 0.001), mid- (P =
      0.001), and posterior (P < 0.001) cingulate cortex; 3) prefrontal cortex gray
      matter (P < 0.001); 4) corona radiata (P < 0.001); 5) secondary sensory cortex (P
      = 0.008); and 6) anterior white matter (P = 0.045), anterior gray matter (P =
      0.002), and posterior gray matter (P = 0.002) insula. No difference was found in
      corpus callosum (P > 0.05). The microstructural changes in some areas correlated
      with clinical parameters such as bloating (anterior insula), mental well-being
      (anterior insula, prefrontal cortex, and mid-cingulated and corona radiata),
      autonomic function based on electrocardiographic results (posterior insula and
      anterior cingulate), and presence of gastroparesis (anterior insula).
      CONCLUSIONS: The findings of this explorative study indicate that microstructural
      changes of brain areas involved in visceral sensory processing are associated
      with autonomic dysfunction and therefore may be involved in the pathogenesis of
      gastrointestinal symptoms in DM patients.

PMID- 23139373
TI  - The fate of taspoglutide, a weekly GLP-1 receptor agonist, versus twice-daily
      exenatide for type 2 diabetes: the T-emerge 2 trial.
AB  - OBJECTIVE: Taspoglutide is a long-acting glucagon-like peptide 1 receptor agonist
      developed for treatment of type 2 diabetes. The efficacy and safety of once
      weekly taspoglutide was compared with twice-daily exenatide. RESEARCH DESIGN AND
      METHODS: Overweight adults with inadequately controlled type 2 diabetes on
      metformin +/- a thiazolidinedione were randomized to subcutaneous taspoglutide 10
      mg weekly (n = 399), taspoglutide 20 mg weekly (n = 398), or exenatide 10 ug
      twice daily (n = 392) in an open-label, multicenter trial. The primary end point
      was change in HbA(1c) after 24 weeks. RESULTS: Mean baseline HbA(1c) was 8.1%.
      Both doses of taspoglutide reduced HbA(1c) significantly more than exenatide
      (taspoglutide 10 mg: -1.24% [SE 0.09], difference -0.26, 95% CI -0.37 to -0.15, P
      < 0.0001; taspoglutide 20 mg: -1.31% [0.08], difference -0.33, -0.44 to -0.22, P
      < 0.0001; exenatide: -0.98% [0.08]). Both taspoglutide doses reduced fasting
      plasma glucose significantly more than exenatide. Taspoglutide reduced body
      weight (taspoglutide 10 mg, -1.6 kg; taspoglutide 20 mg, -2.3 kg) as did
      exenatide (-2.3 kg), which was greater than with taspoglutide 10 mg (P < 0.05).
      HbA(1c) and weight effects were maintained after 52 weeks. More adverse events
      with taspoglutide 10 and 20 mg than exenatide developed over time (nausea in 53,
      59, and 35% and vomiting in 33, 37, and 16%, respectively). Allergic and
      injection-site reactions were more common with taspoglutide. Discontinuations
      were greater with taspoglutide. Antitaspoglutide antibodies were detected in 49%
      of patients. CONCLUSIONS: Once-weekly taspoglutide demonstrated greater glycemic
      control than twice-daily exenatide with comparable weight loss, but with
      unacceptable levels of nausea/vomiting, injection-site reactions, and systemic
      allergic reactions.

PMID- 23139374
TI  - Structured type 1 diabetes education delivered within routine care: impact on
      glycemic control and diabetes-specific quality of life.
AB  - OBJECTIVE: To determine whether improvements in glycemic control and diabetes
      specific quality of life (QoL) scores reported in research studies for the type 1
      diabetes structured education program Dose Adjustment For Normal Eating (DAFNE)
      are also found when the intervention is delivered within routine U.K. health
      care. RESEARCH DESIGN AND METHODS: Before and after evaluation of DAFNE to assess
      impact on glycemic control and QoL among 262 adults with type 1 diabetes.
      RESULTS: There were significant improvements in HbA(1c) from baseline to 6 and 12
      months (from 9.1 to 8.6 and 8.8%, respectively) in a subgroup with suboptimal
      control. QoL was significantly improved by 3 months and maintained at both follow
      up points. CONCLUSIONS: Longer-term improved glycemic control and QoL is
      achievable among adults with type 1 diabetes through delivery of structured
      education in routine care, albeit with smaller effect sizes than reported in
      trials.

PMID- 23139375
TI  - Association between BMI measured within a year after diagnosis of type 2 diabetes
      and mortality.
AB  - OBJECTIVE: To describe the association of BMI with mortality in patients
      diagnosed with type 2 diabetes. RESEARCH DESIGN AND METHODS: Using records of
      106,640 patients in Scotland, we investigated the association between BMI
      recorded around the diagnosis of type 2 diabetes mellitus (T2DM) and mortality
      using Cox proportional hazards regression adjusted for age and smoking status,
      with BMI 25 to <30 kg/m(2) as a referent group. Deaths within 2 years of BMI
      determination were excluded. Mean follow-up to death or the end of 2007 was 4.7
      years. RESULTS: A total of 9,631 deaths occurred between 2001 and 2007. Compared
      with the reference group, mortality risk was higher in patients with BMI 20 to
      <25 kg/m(2) (hazard ratio 1.22 [95% CI 1.13-1.32] in men, 1.32 [1.22-1.44] in
      women) and patients with BMI >=35 kg/m(2) (for example, 1.70 [1.24-2.34] in men
      and 1.81 [1.46-2.24] in women for BMI 45 to <50 kg/m(2)). Vascular mortality was
      higher for each 5-kg/m(2) increase in BMI >30 kg/m(2) by 24% (15-35%) in men and
      23% (14-32%) in women, but was lower below this threshold. The results were
      similar after further adjustment for HbA1c, year of diagnosis, lipids, blood
      pressure, and socioeconomic status. CONCLUSIONS: Patients categorized as normal
      weight or obese with T2DM within a year of diagnosis of T2DM exhibit variably
      higher mortality outcomes compared with the overweight group, confirming a U
      shaped association of BMI with mortality. Whether weight loss interventions
      reduce mortality in all T2DM patients requires study.

PMID- 23139376
TI  - ADHD: Auditory and Visual Stimuli in Automatic and Controlled Processes.
AB  - OBJECTIVE: Deficits in ADHD executive function (EF) task have been widely
      documented in a number of different studies. The aim of this work is to analyze
      the characteristics of auditory vigilance in ADHD and control subjects in two
      conditions: with and without interference. METHOD: in the first study the
      Merrill's (1992) procedure on automaticity with the dual-task interference
      paradigm was used; in the second study the auditory test with automatic procedure
      was used. RESULTS: The results of the study confirm that people with ADHD show
      deficits in auditory vigilance tests and become less careful when interference is
      introduced. CONCLUSION: Results were discussed in terms of a deficit in
      automaticity process.

PMID- 23139377
TI  - Effects on resilience of caregivers of persons with autism spectrum disorder: the
      role of positive cognitions.
AB  - BACKGROUND: Approximately 2.8 million people in the United States are diagnosed
      with autism spectrum disorder (ASD). Family caregivers manage many aspects of
      their care, which is demanding, overwhelming, and can affect their mental health.
      OBJECTIVE: This study examined the effects of caregiver burden (risk factor) and
      positive cognitions (protective factors) on resourcefulness (resilience
      indicator) in 95 caregivers of persons with ASD. DESIGN: Descriptive,
      correlational, and cross-sectional. RESULTS: Positive cognitions explained 32% of
      the variance in resourcefulness, F(1, 93) = 44.49, p < .001, and as positive
      cognitions increased, caregivers' resourcefulness increased. A substantial drop
      in the beta weight of caregiver burden from B = -.36 to -.04 when positive
      cognitions was entered the equation suggested that positive cognitions mediated
      the effect of caregiver burden on resourcefulness. CONCLUSION: The results
      support resilience theory and suggest a need for developing interventions to
      strengthen positive thinking among caregivers of persons with ASD.

PMID- 23139378
TI  - Analysis of the repaglinide concentration increase produced by gemfibrozil and
      itraconazole based on the inhibition of the hepatic uptake transporter and
      metabolic enzymes.
AB  - The plasma concentration of repaglinide is reported to increase greatly when
      given after repeated oral administration of itraconazole and gemfibrozil. The
      present study analyzed this interaction based on a physiologically based
      pharmacokinetic (PBPK) model incorporating inhibition of the hepatic uptake
      transporter and metabolic enzymes involved in repaglinide disposition. Firstly,
      the plasma concentration profiles of inhibitors (itraconazole, gemfibrozil, and
      gemfibrozil glucuronide) were reproduced by a PBPK model to obtain their
      pharmacokinetic parameters. The plasma concentration profiles of repaglinide were
      then analyzed by a PBPK model, together with those of the inhibitors, assuming a
      competitive inhibition of CYP3A4 by itraconazole, mechanism-based inhibition of
      CYP2C8 by gemfibrozil glucuronide, and inhibition of organic anion transporting
      polypeptide (OATP) 1B1 by gemfibrozil and its glucuronide. The plasma
      concentration profiles of repaglinide were well reproduced by the PBPK model
      based on the above assumptions, and the optimized values for the inhibition
      constants (0.0676 nM for itraconazole against CYP3A4; 14.2 MUM for gemfibrozil
      against OATP1B1; and 5.48 MUM for gemfibrozil glucuronide against OATP1B1) and
      the fraction of repaglinide metabolized by CYP2C8 (0.801) were consistent with
      the reported values. The validity of the obtained parameters was further
      confirmed by sensitivity analyses and by reproducing the repaglinide
      concentration increase produced by concomitant gemfibrozil administration at
      various timings/doses. The present findings suggested that the reported
      concentration increase of repaglinide, suggestive of synergistic effects of the
      coadministered inhibitors, can be quantitatively explained by the simultaneous
      inhibition of the multiple clearance pathways of repaglinide.

PMID- 23139379
TI  - Species differences in biliary clearance and possible relevance of hepatic uptake
      and efflux transporters involvement.
AB  - From a search of the available literature, a database of 22 drugs of all charge
      types and several different therapeutic classes was compiled to compare rat and
      human biliary clearance data. Dog biliary excretion data were also found for nine
      of the drugs. For 19 of the 22 drugs (86%), rat unbound biliary clearance values,
      when normalized for body weight, exceeded those for humans by factors ranging
      from 9 to over 2500-fold, whereas human/dog differences were much less dramatic.
      It was possible to define hepatic uptake and efflux transporter involvement for
      many of the drugs. On the basis of the findings, it is postulated that regardless
      of the biliary efflux transporters implicated, when drugs do not require active
      hepatic uptake to access the liver there may be fairly insignificant differences
      in rat, dog, and human biliary clearance. Conversely, when the organic anion
      transporting polypeptide drug transporters are involved, one may expect at least
      a 10-fold discrepancy in rat to human biliary clearance normalized for body
      weight and corrected for plasma protein binding.

PMID- 23139380
TI  - Matricellular proteins and matrix metalloproteinases mark the inflammatory and
      fibrotic response in human cardiac allograft rejection.
AB  - AIMS: The cardiac extracellular matrix is highly involved in regulating
      inflammation, remodelling, and function of the heart. Whether matrix alterations
      relate to the degree of inflammation, fibrosis, and overall rejection in the
      human transplanted heart remained, until now, unknown. METHODS AND RESULTS:
      Expression of matricellular proteins, proteoglycans, and metalloproteinases
      (MMPs) and their inhibitors (TIMPs) were investigated in serial endomyocardial
      biopsies (n = 102), in a cohort of 39 patients within the first year after
      cardiac transplantation. Out of 15 matrix-related proteins, intragraft transcript
      and protein levels of syndecan-1 and MMP-9 showed a strong association with the
      degree of cardiac allograft rejection (CAR), the expression of pro-inflammatory
      cytokines tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and transforming
      growth factor (TGF)-beta, and with infiltrating CD3+ T-cells and CD68+ monocytes.
      In addition, SPARC, CTGF, TSP-2, MMP-14, TIMP-1, Testican-1, TSP-1, Syndecan-1,
      MMP-2, -9, and -14, as well as IL-6 and TGF-beta transcript levels and
      inflammatory infiltrates all strongly relate to collagen expression in the
      transplanted heart. More importantly, receiver operating characteristic curve
      analysis demonstrated that syndecan-1 and MMP-9 transcript levels had the highest
      area under the curve (0.969 and 0.981, respectively), thereby identifying both as
      a potential decision-making tool to discriminate rejecting from non-rejecting
      hearts. CONCLUSION: Out of 15 matrix-related proteins, we identified synd-1 and
      MMP-9 intragraft transcript levels of as strong predictors of human CAR. In
      addition, a multitude of non-structural matrix-related proteins closely associate
      with collagen expression in the transplanted heart. Therefore, we are convinced
      that these findings deserve further investigation and are likely to be of
      clinical value to prevent human CAR.

PMID- 23139381
TI  - Identification of autophosphorylation inhibitors of the inositol-requiring enzyme
      1 alpha (IRE1alpha) by high-throughput screening using a DELFIA assay.
AB  - Inositol-requiring enzyme 1 alpha (IRE1alpha) is a transmembrane sensor protein
      with both kinase and ribonuclease activity, which plays a crucial role in the
      unfolded protein response (UPR). Protein misfolding in the endoplasmic reticulum
      (ER) lumen triggers dimerization and subsequent trans-autophosphorylation of
      IRE1alpha. This leads to the activation of its endoribonuclease (RNase) domain
      and splicing of the mRNA of the transcriptional activator XBP1, ultimately
      generating an active XBP1 (XBP1s) implicated in multiple myeloma survival.
      Previously, we have identified human IRE1alpha as a target for the development of
      kinase inhibitors that could modulate the UPR in human cells, which has
      particular relevance for multiple myeloma and other secretory malignancies. Here
      we describe the development and validation of a 384-well high-throughput
      screening assay using DELFIA technology that is specific for IRE1alpha
      autophosphorylation. Using this format, a focused library of 2312 potential
      kinase inhibitors was screened, and several novel IRE1alpha kinase inhibitor
      scaffolds were identified that could potentially be developed toward new
      therapies to treat multiple myeloma.

PMID- 23139382
TI  - Parallel screening of low molecular weight fragment libraries: do differences in
      methodology affect hit identification?
AB  - Fragment screening is becoming widely accepted as a technique to identify hit
      compounds for the development of novel lead compounds. In neighboring
      laboratories, we have recently, and independently, performed a fragment screening
      campaign on the HIV-1 integrase core domain (IN) using similar commercially
      purchased fragment libraries. The two campaigns used different screening methods
      for the preliminary identification of fragment hits; one used saturation transfer
      difference nuclear magnetic resonance spectroscopy (STD-NMR), and the other used
      surface plasmon resonance (SPR) spectroscopy. Both initial screens were followed
      by X-ray crystallography. Using the STD-NMR/X-ray approach, 15 IN/fragment
      complexes were identified, whereas the SPR/X-ray approach found 6 complexes. In
      this article, we compare the approaches that were taken by each group and the
      results obtained, and we look at what factors could potentially influence the
      final results. We find that despite using different approaches with little
      overlap of initial hits, both approaches identified binding sites on IN that
      provided a basis for fragment-based lead discovery and further lead development.
      Comparison of hits identified in the two studies highlights a key role for both
      the conditions under which fragment binding is measured and the criteria selected
      to classify hits.

PMID- 23139383
TI  - Vesicular signalling and immune modulation as hedonic fingerprints: proteomic
      profiling in the chronic mild stress depression model.
AB  - Extensive preclinical research has focused at unravelling the underlying
      molecular mechanisms leading to depression and recovery. In this study, we
      investigated the quantitative changes in protein abundance in the ventral
      hippocampal granular cell layer. We compared different phenotypes from the
      chronic mild stress (CMS) model of depression using chronic administration with
      two selective serotonin reuptake inhibitors (SSRIs), escitalopram and sertraline.
      We isolated granular cells using Laser-Capture Microdissection (LCM) and we
      identified their regulated proteins using two-dimensional (2D) differential gel
      electrophoresis (DIGE) and tandem mass spectrometry (MS/MS). The majority of the
      proteins we identified were enzymes involved in different metabolic activities.
      Additional proteins were functionally classified as vesicular proteins and immune
      system proteins. Rab GDP dissociation inhibitor alpha (GDIA) and syntaxin-binding
      protein 1 (STXB1) were potential markers for stress reactivity. Dynamin 1 (DYN1),
      glutathione S-transferase omega-1 (GSTO1) and peroxiredoxin (PRDX6) were
      associated with treatment response. In addition, an imbalance between different
      post-translationally modified versions of DYN1 and GSTO1 potentially accounted
      for SSRI treatment refraction. In the present study, we searched for new markers
      of stress reactivity and treatment response as well as any underlying molecular
      mechanisms correlating to the development of anhedonia and antidepressant therapy
      refraction. Our results pointed towards an essential role of post-translational
      modifications in both vesicular and immune protein systems.

PMID- 23139384
TI  - Responses to environmental smoking in never-smoking children: can symptoms of
      nicotine addiction develop in response to environmental tobacco smoke exposure?
AB  - A recent line of studies has brought attention to the question whether repeated
      exposure to environmental tobacco smoke (ETS) is capable of producing psycho
      physiological effects in non-smokers and whether symptoms of nicotine dependence
      can develop in the absence of active smoking. Children seem to be particularly
      vulnerable to the effects of ETS. We examined the occurrence of psycho
      behavioural symptoms, designed to assess nicotine addiction and nicotine
      withdrawal, in a sample of 778 never-smoking children aged 9-12 years using cross
      sectional survey data collected in 15 Dutch primary schools. In the present
      study, 6% of never-smoking children reported symptoms of craving, 8% reported cue
      triggered wanting to smoke, and 20% reported subjective symptoms in response to
      ETS exposure. In never-smoking children, a higher number of smokers in the
      child's social environment was associated with more symptoms of cue-triggered
      wanting to smoke and more subjective symptoms in response to ETS. Never-smoking
      children and children who had initiated smoking were equally likely to report
      subjective symptoms in response to ETS exposure. In conclusion, environmental
      smoking is associated with self-reported psycho-behavioural symptoms in never
      smoking children. Future research needs to investigate whether symptoms in
      children exposed to ETS are physiologically based or whether they reflect other
      characteristics which predispose youth for smoking initiation in the future.

PMID- 23139385
TI  - MicroRNA-101, mitogen-activated protein kinases and mitogen-activated protein
      kinases phosphatase-1 in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is the prototype of human autoimmune disease
      in which various inflammatory cytokines such as tumor necrosis factor-alpha (TNF
      alpha), interleukin (IL)-1, IL-6 and interferon (IFN) play crucial pathogenic
      roles. The production of these cytokines is responsible for the mitogen-activated
      protein kinases (MAPKs), which can also generate mitogen-activated protein
      kinases phosphatases (MKPs). MKP-1, a prototypical member of the MKP family that
      can influence outcomes of autoimmune diseases and reduce the inflammatory
      cytokines by dephosphorylation of p38 and JNK MAPK, plays a critical role in the
      expression of inflammatory mediators at transcriptional and post-transcriptional
      levels. MicroRNA-101 (miR) is a small non-coding RNA that regulates the MAPK
      response by targeting MKP-1 mRNA 3'-UTR, and affects the secretion of the
      downstream inflammatory cytokines. However, the interaction among the above three
      in the pathogenesis of SLE has not previously been reported. This review
      discusses the current understanding of the role of the MAPK/MKP/miR-101 axis in
      regulating immune responses and the pathogenesis of SLE to provide new ideas for
      clinical treatment of SLE.

PMID- 23139386
TI  - Increased iron accumulation occurs in the earliest stages of demyelinating
      disease: an ultra-high field susceptibility mapping study in Clinically Isolated
      Syndrome.
AB  - OBJECTIVE: To determine, using ultra-high field magnetic resonance imaging (MRI),
      whether changes in iron content occur in the earliest phases of demyelinating
      disease, by quantifying the magnetic susceptibility of deep grey matter
      structures in patients with Clinically Isolated Syndrome (CIS) that is suggestive
      of multiple sclerosis (MS), as compared with age-matched healthy subjects.
      METHODS: We compared 19 CIS patients to 20 age-matched, healthy controls.
      Scanning of the study subjects was performed on a 7T Philips Achieva system,
      using a 3-dimensional, T2*-weighted gradient echo acquisition. Phase data were
      first high-pass filtered, using a dipole fitting method, and then inverted to
      produce magnetic susceptibility maps. Region of interest (ROI) analysis was used
      to estimate magnetic susceptibility values for deep grey matter structures
      (caudate nucleus, putamen, globus pallidus, the thalamus and its pulvinar).
      RESULTS: Significantly increased relative susceptibilities were found in the CIS
      group, compared with controls, for the caudate nucleus (p = < 0.01), putamen (p <
      0.01), globus pallidus (p < 0.01) and pulvinar (p < 0.05). We found no
      significant nor consistent trends in the relationship between susceptibility and
      age for either the study controls or CIS patients, in any ROI (r(2) < 0.5; p >
      0.05). In CIS patients, the time elapsed since the clinical event and the
      Expanded Disability Status Scale (EDSS) scores were not correlated with iron
      levels in any ROI (r(2) < 0.5; p > 0.05); however, a moderate correlation (r(2) =
      0.3; p < 0.01) was found between the T1 lesion load and the mean susceptibility
      of the caudate nucleus. CONCLUSION: CIS patients showed an increased iron
      accumulation, as measured using susceptibility mapping of the deep grey matter,
      suggesting that iron changes did occur at the earlier stages of CIS disease.

PMID- 23139387
TI  - Alpha actinin is specifically recognized by Multiple Sclerosis autoantibodies
      isolated using an N-glucosylated peptide epitope.
AB  - Sophisticated approaches have recently led to the identification of novel
      autoantigens associated with Multiple Sclerosis (MuS), e.g. neurofascin,
      contactin, CNPase, and other T-cell receptor membrane anchored proteins. These
      putative antigens, although differing from the conventional myelin derivatives,
      are conceptually based on an animal model of experimental autoimmune
      encephalomyelitis. In this report we describe the identification of putative
      antigens based on their recognition by autoantibodies isolated from MuS patient
      serum. In a previous work from this laboratory we have shown that a peptide
      probe, named CSF114(Glc), specifically identifies serum autoantibodies in a
      subset of MuS patients, representing ~30% of the patient population. The
      autoantibodies, purified from MuS patients' sera (six), through CSF114(Glc)
      affinity chromatography, detected three immunoreactive protein bands present in
      the rat brain. Proteomic analysis of the immunoreactive bands, involving MALDI
      and MS/MS techniques, revealed the presence of four proteins distinguishable by
      their mass: alpha fodrin, alpha actinin 1, creatine kinase, and CNPase. The
      immunoreactive profile of these rat brain proteins was compared with that of
      commercially available standard proteins by challenging against either
      CSF114(Glc) purified MuS autoantibodies, or monoclonal antibodies. Further
      discrimination among the rat brain proteins was provided by the following
      procedure: whereas monoclonal antibodies recognized all rat brain proteins,
      isolated MuS specific antibodies recognize only alpha actinin 1 as a putative
      antigen. In fact, alpha actinin 1 displayed a robust immunoreactive response
      against all MuS patients' sera examined, whereas the other three bands were not
      consistently detectable. Thus, alpha actinin 1, a cytoskeleton protein implicated
      in inflammatory/degenerative autoimmune diseases (lupus nephritis and autoimmune
      hepatitis) might be regarded as a novel MuS autoantigen, perhaps a prototypic
      biomarker for the inflammatory/degenerative process typical of the disease.

PMID- 23139388
TI  - Assessing the effectiveness of intuitive eating for weight loss - pilot study.
AB  - The obesity epidemic is widely recognized as a major public health issue
      resulting in chronic diseases. Calorie restriction (CR) is frequently used for
      most weight loss programs. The intuitive eating (IE) approach uses an
      individual's response to internal cues of hunger, satiety, and appetite and
      replaces CR. The study was a randomized controlled trial with two groups that
      assessed the anthropometric measurements of obese adults using CR and IE to
      achieve weight loss. The participants were sedentary obese individuals with no
      history of chronic diseases. They engaged in physical activity three times per
      week for 30 minutes and recorded their daily food intake in a food diary.
      Instructions were given for the CR and IE at the start and midpoint of the study.
      The duration of the study was 6 weeks. Weight and waist circumference were
      measured and body mass index calculated. total weight loss was significantly
      (p=0.03) lower in the CR group than in the IE group. The CR group lost weight
      consistently throughout the study, whereas weight loss in the IE group was
      significantly less at the endpoint than at the midpoint. Calorie restriction is a
      superior approach to weight management than IE.

PMID- 23139390
TI  - Biodefense and dual-use research: the optimisation problem and the value of
      security.

PMID- 23139389
TI  - A culturally specific dietary plan to manage weight gain among African American
      breast cancer survivors: a feasibility study.
AB  - Breast cancer survival rates are lower in African Americans (AAs) than in
      Caucasians, owing in part to a higher prevalence of obesity in the former, which
      increases the risk of recurrence and mortality. The Women's Intervention
      Nutrition Study (WINS) found that Caucasian women who followed a low-fat eating
      plan experienced a lower rate of cancer recurrence than women who maintained
      their usual diets. The purpose of this study was to test the feasibility of a
      WINS plan tailored to the cultural needs of AA breast cancer survivors. This
      feasibility pilot study was conducted at a university National Cancer Institute
      designated comprehensive cancer center outpatient clinic with AA breast cancer
      survivors. The culturally specific WINS (WINS-c) plan included eight individual
      counseling sessions, five educational group meetings, and follow-up telephone
      calls over a 1-year period. Outcome measures included dietary fat, triglyceride,
      insulin and glucose levels, and fruit and vegetable intake. Participants (n = 8)
      had a mean age of 61.1 years (standard error of the mean (SEM) 3.1 years) and a
      mean BMI of 32 kg/m(2) (SEM 4.25 kg/m)(2). Baseline daily fat consumption
      decreased from 64.6 g (range 36.8-119.6g) to 44.0 g (21.6-73.4g) at 52 weeks (p =
      0.07). Mean daily consumption of fruits and vegetables increased by 36% and 15%,
      respectively. Mean triglyceride levels decreased at 12 months (p < 0.05).
      Sustained hyperinsulinemia was noted in most participants, including those
      without diabetes. Mean calcium and vitamin D consumption decreased over the 1
      year study period. In AA breast cancer survivors, the WINS-c program resulted in
      a trend toward reduced fat consumption and may represent a sustainable approach
      in this population for improvement of diet quality after breast cancer.

PMID- 23139391
TI  - Including patients in resuscitation decisions in Switzerland: from doing more to
      doing better.
AB  - BACKGROUND: Decisions regarding Cardio-Pulmonary Resuscitation (CPR) and Do Not
      Attempt Resuscitation (DNAR) orders remain demanding, as does including patients
      in the process. OBJECTIVES: To explore physicians' justification for CPR/DNAR
      orders and decisions regarding patient inclusion, as well as their reports of how
      they initiated discussions with patients. METHODS: We administered a face-to-face
      survey to residents in charge of 206 patients including DNAR and CPR orders, with
      or without patient inclusion. RESULTS: Justifications were provided for 59% of
      DNAR orders and included severe comorbidity, patients and families' resuscitation
      preferences, patients' age, or poor prognosis or quality of life. Reasons to
      include patients in CPR/DNAR decisions were provided in 96% and 84% of cases, and
      were based on respect for autonomy, clinical assessment of the situation as not
      too severe, and the view that such inclusion was required. Reasons for not
      including patients were offered in 84% of cases for CPR and in 70% for DNAR. They
      included absent decision-making capacity, a clinical situation viewed as good
      (CPR) or offering little hope of recovery (DNAR), barriers to communication, or
      concern that discussions could be emotionally difficult or superfluous. Decisions
      made earlier in the patient's management were infrequently viewed as requiring
      revision. Residents reported a variety of introductions to discussions with
      patients. CONCLUSIONS: These results provide better understanding of reasons for
      CPR/DNAR decisions, reasons for patient inclusion or lack thereof, and ways in
      which such inclusion is initiated. They also point to potential side-effects of
      implementing CPR/DNAR recommendations without in-depth and practical training.
      This should be part of a regular audit and follow-up process for such
      recommendations.

PMID- 23139392
TI  - Documented consent process for implantable cardioverter-defibrillators and
      implications for end-of-life care in older adults.
AB  - Implantable cardioverter defibrillators (ICDs) reduce mortality in selected
      patients at risk for life-threatening heart arrhythmias, and their use is
      increasingly common. However, these devices also confer risk for delivery of
      unexpected painful shocks during the dying process, thus reducing the quality of
      palliative care at the end of life. This scenario can be avoided by ICD
      deactivation in appropriate circumstances but patients will remain unaware of
      this option if not informed about it. It is not known how often end-of-life
      implications are discussed with patients prior to ICD implantation, when focus is
      primarily on the short-term potential complications of the device placement
      procedure itself. We conducted a retrospective chart review to determine how
      often end-of-life implications were discussed with patients as part of the
      informed consent process. We evaluated consent forms and related other chart
      documentation for 91 patients (ranging from age 60 to 89 years) undergoing first
      time ICD placement at a mid-western academic medical center from 2006-2008. Only
      one chart documented any discussion of end-of-life implications, in a case where
      the issue was raised by a patient who noted that quality of life was their main
      focus. Consent was provided by a health care surrogate in only four of the 91
      cases. In conclusion, patients giving consent for ICD implantation may be
      uninformed about the device's potential future impact on end-of-life care, the
      dying process, and the option for device deactivation. Truly informed consent
      requires that both short- and long-term potential implications be reviewed with
      patients.

PMID- 23139394
TI  - Good grief: bereavement literature for young adults and A Monster Calls.
AB  - Recent years have seen a proliferation of critically acclaimed novels for young
      adults dealing with bereavement. This is part of a 'bereavement turn'--a
      contemporary cultural movement to examine publicly our attitudes to death and
      grieving. This paper examines the narrative strategies in Patrick Ness's award
      winning novel A Monster Calls to look at the ways in which the psychic burden of
      the impending loss of a parent through cancer is managed. The book draws on
      conventions of children's literature to create a sense of familiarity that helps
      to balance the emotional stress of the story. The Kubler-Ross stages of grief
      serve as a heuristic that helps the story deliver catharsis in spite of its
      inevitably traumatic subject matter. A Monster Calls is an important addition to
      the canon of fictional pathography.

PMID- 23139393
TI  - Embryo deaths in reproduction and embryo research: a reply to Murphy's double
      effect argument.
AB  - The majority of embryos created in natural reproduction die spontaneously within
      a few weeks of conception. Some have argued that, therefore, if one believes the
      embryo is a person (in the normative sense) one should find 'natural'
      reproduction morally problematic. An extension of this argument holds that, if
      one accepts embryo deaths in natural reproduction, consistency requires that one
      also accepts embryo deaths that occur in (i) assisted reproduction via in vitro
      fertilisation (IVF) and (ii) embryo research. In a recent paper in this journal,
      Timothy Murphy criticises both the initial argument and its extension. Murphy
      argues that double-effect reasoning can justify embryo deaths both in natural
      reproduction and IVF, but not in embryo research. Thus, according to Murphy, one
      can, without being inconsistent, (1) believe the embryo is a person and accept
      natural reproduction and IVF, and (2) accept natural reproduction and IVF, while
      rejecting embryo research on the ground that it involves embryo deaths. I show
      that Murphy's argument is problematic because double effect cannot justify embryo
      deaths in standard IVF practices. The problem is that the proportionality
      criterion of double effect is not met by such practices. Thus, Murphy's argument
      fails to support (1) and (2). An implication of his argument failing to support
      (2) is that it does not defeat the position I have defended in the past-that if
      one accepts standard IVF practices one should also accept embryo research,
      including research with embryos created solely for that purpose. 

PMID- 23139395
TI  - Antimicrobial susceptibility pattern of beta-haemolytic group A, C and G
      streptococci isolated from North India.
AB  - The objective of this study was to determine the antibiotic resistance amongst
      beta-haemolytic streptococci (BHS) from North India. A total of 155 BHS isolates,
      comprising group A streptococci (GAS) (102), group C streptococci (GCS) (25) and
      group G streptococci (GGS) (28), collected from patients with pharyngitis,
      rheumatic fever, skin disease and invasive disease were analysed for their
      antimicrobial susceptibility to 20 antibiotics using the Kirby-Bauer disc
      diffusion method. The MICs of penicillin, tetracycline, clarithromycin,
      azithromycin and erythromycin were also determined using the HiComb test,
      following the Clinical and Laboratory Standards Institute guidelines. The results
      showed that 37.4% of BHS isolates were susceptible to all antibiotics and 19.4%
      were highly resistant to tetracycline; however, only 2.6-5.2% were resistant to
      macrolides. The tetracycline resistance (P<0.05) of BHS was found to be
      statistically significant. GAS isolates from different sources of infection also
      showed statistically significant antibiotic resistance to azithromycin (P=0.029).
      Multi-drug resistance was found irrespective of streptococcal emm types. No
      association between GAS emm types and drug resistance was seen. MIC determination
      showed all isolates to be susceptible to the five antibiotics tested, except for
      two GAS and one GGS isolates that were resistant to clarithromycin, and one GAS
      skin isolate that was resistant to tetracycline. This study suggests that the
      variation in antibiotic resistance amongst BHS isolates from North India is
      independent of the isolation source and emm type distribution, hence emphasizing
      the need for a longitudinal surveillance in different regions of India.

PMID- 23139396
TI  - Rapid identification of Gram-positive pathogens and their resistance genes from
      positive blood culture broth using a multiplex tandem RT-PCR assay.
AB  - The early initiation of targeted antibiotic therapy in patients with bacteraemia
      and septic shock impacts favourably on outcomes. Rapid methods are therefore
      increasingly employed for bacterial identification directly from positive blood
      culture bottles, but with variable success. We evaluated the performance of the
      Gram Positive 12 multiplex tandem PCR (MT-PCR) assay (AusDiagnostics; catalogue
      no. 6202, version 07) containing targets for the identification of staphylococci
      including Staphylococcus aureus, streptococci including Streptococcus pneumoniae,
      enterococci including Enterococcus faecalis and Enterococcus faecium and their
      common antibiotic resistance genes (mecA, vanA, vanB). A total of 673 aerobic and
      anaerobic blood culture broths demonstrating Gram-positive cocci on microscopy
      were analysed in parallel with traditional phenotypic methods. Amplification of
      the internal control was inhibited in 79/673 (11.7 %) samples; however, MT-PCR
      identification was in concordance with phenotypic identification to the genus
      level in 96.6 % (537/556) of the remaining monomicrobial specimens and to the
      species level, where applicable, in 100 % (172/172) of samples. MT-PCR
      identification for 94.7 % (36/38) of polymicrobial samples matched traditional
      phenotypic identification. Meticillin and vancomycin susceptibility results
      determined by MT-PCR in blood culture broths demonstrated complete agreement with
      those determined by phenotypic methods in all 143 Staphylococcus aureus isolates
      and eight E. faecium isolates, respectively. Gram-positive pathogens and their
      key antibiotic resistance markers were reliably identified with the MT-PCR assay
      within 3 h of a positive blood culture result.

PMID- 23139398
TI  - The importance of myeloperoxidase enzyme activity in the pathogenesis of Crimean
      Congo haemorrhagic fever.
AB  - Crimean-Congo haemorrhagic fever (CCHF) is a disease with a severe course
      including acute viral haemorrhagic fever, ecchymosis, thrombocytopenia, hepatic
      function disorder and high mortality. Myeloperoxidase (MPO) is an enzyme located
      in neutrophil granulocytes and plays an important role in the destruction of
      phagocytosed micro-organisms. The aim of this study was to analyse MPO enzyme
      activity in CCHF cases compared with a control group. A total of 47 randomly
      selected CCHF patients admitted to the Department of Infectious Diseases of
      Cumhuriyet University Hospital in Sivas, Turkey, were studied, and as a control
      group, 41 age- and sex-matched individuals without any systemic disease were
      included in this study. MPO enzyme activity was measured in plasma and leukocytes
      for both groups by the ELISA method. MPO plasma and MPO leukocyte values were
      calculated as 57.62 +/- 8.85 and 44.84 +/- 9.71 in CCHF patients, and 0.79 +/-
      0.29 and 0.49 +/- 0.11 in the controls, respectively. MPO enzyme activity was
      statistically significantly higher in patients with CCHF when compared to the
      control group. In conclusion, MPO enzyme activity is directly related to the
      activation of phagocytic leukocytes, and increases in both the plasma and
      leukocytes in CCHF patients. The increase of the MPO enzyme activity in
      leukocytes due to viral load leads to the destruction of the leukocyte. It is
      thought that MPO enzyme activity in plasma was higher in CCHF patients due to the
      destruction of leukocytes. MPO enzyme activity may be important in terms of the
      prognosis in patients with CCHF; however, more extensive studies are required on
      this subject.

PMID- 23139397
TI  - Performance of culture media for the isolation and identification of
      Staphylococcus aureus from bovine mastitis.
AB  - Rapid isolation and identification of pathogens is a major goal of diagnostic
      microbiology. In order to isolate and identify Staphylococcus aureus, a number of
      authors have used a variety of selective and/or differential culture media.
      However, to date, there are no reports comparing the efficacy of selective and
      differential culture media for S. aureus isolation from bovine mastitis cases
      using the 16S rRNA (rrs) gene sequence as a gold standard test. In the present
      study, we evaluated the efficacy of four selective and/or differential culture
      media for the isolation of S. aureus from milk samples collected from cows
      suffering from bovine mastitis. Four hundred and forty isolates were obtained
      using salt-mannitol agar (SMA, Bioxon), Staphylococcus-110 agar (S110, Bioxon),
      CHROMAgar Staph aureus (CSA, BD-BBL) and sheep's blood agar (SBA, BD-BBL). All
      bacterial isolates were identified by their typical colony morphology in the
      respective media, by secondary tests (for coagulase and beta-haemolysis) and by
      partial 16S rRNA (rrs) gene sequencing as a gold standard test. Sensitivity,
      positive predictive and negative predictive values were higher for SMA (86.96,
      52.63 and 95.95%, respectively) compared with S110 (70.00, 23.73 and 90.91%,
      respectively), CSA (69.23, 28.13 and 95.74%, respectively) and SBA (68.75, 37.93
      and 89.58%, respectively) while specificity values were similar for all media.
      Data indicated that the use of culture media for S. aureus isolation combined
      with determination of coagulase activity and haemolysis as secondary tests
      improved accuracy of the identification and was in accordance with rrs gene
      sequence-analysis compared with the use of the culture media alone.

PMID- 23139399
TI  - A supplemented soft agar chemotaxis assay demonstrates the Helicobacter pylori
      chemotactic response to zinc and nickel.
AB  - Directed motility, or chemotaxis, is required for Helicobacter pylori to
      establish infection in the stomach, although the full repertoire of this
      bacterium's chemotactic responses is not yet known. Here we report that H. pylori
      responds to zinc as an attractant and nickel as a repellent. To reach this
      conclusion, we employed both a temporal chemotaxis assay based on bacterial
      reversals and a supplemented soft agar spatial assay. We refined the temporal
      assay using a previously described chemorepellent, acid, and found that H. pylori
      requires rich media with serum to maintain optimal swimming motility.
      Surprisingly, we found that some strains respond to acid as an attractant, and
      that the TlpC chemoreceptor correlated with whether acid was sensed as an
      attractant or repellent. Using this same assay, we detected weak repellent
      responses to nickel and copper, and a varied response to zinc. We thus developed
      an alternative spatial chemotactic assay called the supplemented soft agar assay,
      which utilizes soft agar medium supplemented with the test compound. With
      Escherichia coli, the attractant serine slowed overall bacterial migration, while
      the repellent nickel increased the speed of overall migration. In H. pylori we
      detected slowed migration with doubled tryptone media, as well as zinc,
      consistent with an attractant response. In contrast, nickel increased migration,
      consistent with repulsion.

PMID- 23139400
TI  - Dual role of CcpC protein in regulation of aconitase gene expression in Listeria
      monocytogenes and Bacillus subtilis.
AB  - The role of the CcpC regulatory protein as a repressor of the genes encoding the
      tricarboxylic acid branch enzymes of the Krebs cycle (citrate synthase, citZ;
      aconitase, citB; and isocitrate dehydrogenase, citC) has been established for
      both Bacillus subtilis and Listeria monocytogenes. In addition, hyperexpression
      of citB-lacZ reporter constructs in an aconitase null mutant strain has been
      reported for B. subtilis. We show here that such hyperexpression of citB occurs
      in L. monocytogenes as well as in B. subtilis and that in both species the
      hyperexpression is unexpectedly dependent on CcpC. We propose a revision of the
      existing CcpC-citB regulatory scheme and suggest a mechanism of regulation in
      which CcpC represses citB expression at low citrate levels and activates citB
      expression when citrate levels are high.

PMID- 23139401
TI  - Helicobacter hepaticus NikR controls urease and hydrogenase activities via the
      NikABDE and HH0418 putative nickel import proteins.
AB  - Helicobacter hepaticus open reading frame HH0352 was identified as a nickel
      responsive regulator NikR. The gene was disrupted by insertion of an erythromycin
      resistance cassette. The H. hepaticus nikR mutant had five- to sixfold higher
      urease activity and at least twofold greater hydrogenase activity than the wild
      type strain. However, the urease apo-protein levels were similar in both the wild
      type and the mutant, suggesting the increase in urease activity in the mutant was
      due to enhanced Ni-maturation of the urease. Compared with the wild-type strain,
      the nikR strain had increased cytoplasmic nickel levels. Transcription of nikABDE
      (putative inner membrane Ni transport system) and hh0418 (putative outer membrane
      Ni transporter) was nickel- and NikR-repressed. Electrophoretic mobility shift
      assays (EMSAs) revealed that purified HhNikR could bind to the nikABDE promoter
      (P(nikA)), but not to the urease or the hydrogenase promoter; NikR-P(nikA)
      binding was enhanced in the presence of nickel. Also, qRT-PCR and EMSAs indicated
      that neither nikR nor the exbB-exbD-tonB were under the control of the NikR
      regulator, in contrast with their Helicobacter pylori homologues. Taken together,
      our results suggest that HhNikR modulates urease and hydrogenase activities by
      repressing the nickel transport/nickel internalization systems in H. hepaticus,
      without direct regulation of the Ni-enzyme genes (the latter is the case for H.
      pylori). Finally, the nikR strain had a two- to threefold lower growth yield than
      the parent, suggesting that the regulatory protein might play additional roles in
      the mouse liver pathogen.

PMID- 23139403
TI  - Fifteen years of research on nephrin: what we still need to know.

PMID- 23139402
TI  - Maternal smoking as a model for environmental epigenetic changes affecting
      birthweight and fetal programming.
AB  - Although the association between maternal smoking and low birthweight infants has
      been well established, the mechanisms behind reduced fetal growth are still being
      elucidated. While many infants are exposed to tobacco smoke in utero, not all are
      born growth restricted or small for gestational age. Many hypotheses have emerged
      to explain the differential response to in utero maternal tobacco smoke exposure
      (MTSE). Studies have shown that both maternal and fetal genotypes may contribute
      to the discrepant outcomes. However, the contribution of epigenetic changes
      cannot be ignored. In this review we address two important questions regarding
      the effect of MTSE on the fetal epigenome. First, does exposure to maternal
      tobacco smoke in utero alter the fetal epigenome? Secondly, could these
      alterations be associated with the reduced fetal growth observed with MTSE?

PMID- 23139404
TI  - Out of control: accelerated aging in uremia.
AB  - Next to a high morbidity, patients with end-stage renal failure (ESRD) suffer
      from a complex spectrum of clinical manifestations. Both the phenotype of
      patients with ESRD as well as the pathophysiology of uremia show interesting
      parallels with the general aging process. Phenotypically, patients with ESRD have
      an increased susceptibility for both cardiovascular as well as infectious disease
      and show a reduction in functional capacity as well as muscular mass
      (sarcopenia), translating into a high prevalence of frailty also in younger
      patients. Pathophysiologically, the immune dysfunction, telomere attrition and
      the presence of low-grade inflammation in uremic patients also show parallels
      with the aging process. System models of aging, such as the homeodynamic model
      and reliability theory of Gavrilov may also have relevance for ESRD. The
      reduction in the redundancy of compensatory mechanisms and the multisystem
      impairment in ESRD explain the rapid loss of homeodynamic/homeostatic balance and
      the increased susceptibility to external stressors in these patients. System
      theories may also explain the relative lack of success of interventions focusing
      on single aspects of renal disease. The concept of accelerated aging, which also
      shares similarities with other organ diseases, may be of relevance both for a
      better understanding of the uremic process, as well as for the design of
      multidimensional interventions in ESRD patients, including an important role for
      early rehabilitation. Research into processes akin to both aging and uremia may
      result in novel therapeutic approaches.

PMID- 23139405
TI  - There's nothing that succeeds like failure: discerning the woods from the trees
      in smoking cessation debates.

PMID- 23139406
TI  - Research priorities for Article 14--demand reduction measures concerning tobacco
      dependence and cessation.
AB  - INTRODUCTION: Tobacco dependence treatment (TDT) interventions are often seen as
      expensive with little impact on the prevalence of tobacco use. However,
      activities that promote the cessation of tobacco use and support abstinence have
      an important role in any comprehensive tobacco control program and as such are
      recognized within Article 14 (A14) of the Framework Convention on Tobacco
      Control. OBJECTIVES: To review current evidence for TDT and recommend research
      priorities that will contribute to more people being helped to stop tobacco use.
      METHODS: We used the recommendations within the A14 guidelines to guide a review
      of current evidence and best practice for promotion of tobacco cessation and TDT,
      identify gaps, and propose research priorities. RESULTS: We identified nine areas
      for future research (a) understanding current tobacco use and the effect of
      policy on behavior, (b) promoting cessation of tobacco use, (c) implementation of
      TDT guidelines, (d) increasing training capacity, (e) enhancing population-based
      TDT interventions, (f) treatment for different types of tobacco use, (g) supply
      of low-cost pharmaceutical devices/ products, (h) investigation use of
      nonpharmaceutical devices/ products, and (i) refinement of current TDTs. Specific
      research topics are suggested within each of these areas and recognize the
      differences needed between high- and low-/middle-income countries. CONCLUSIONS:
      Research should be prioritized toward examining interventions that (a) promote
      cessation of tobacco use, (b) assist health care workers provide better help to
      smokers (e.g., through implementation of guidelines and training), (c) enhance
      population-based TDT interventions, and (d) assist people to cease the use of
      other tobacco products.

PMID- 23139407
TI  - Ca intercalated bilayer graphene as a thinnest limit of superconducting C6Ca.
AB  - Success in isolating a 2D graphene sheet from bulky graphite has triggered
      intensive studies of its physical properties as well as its application in
      devices. Graphite intercalation compounds (GICs) have provided a platform of
      exotic quantum phenomena such as superconductivity, but it is unclear whether
      such intercalation is feasible in the thinnest 2D limit (i.e., bilayer graphene).
      Here we report a unique experimental realization of 2D GIC, by fabricating
      calcium-intercalated bilayer graphene C(6)CaC(6) on silicon carbide. We have
      investigated the structure and electronic states by scanning tunneling microscopy
      and angle-resolved photoemission spectroscopy. We observed a free-electron-like
      interlayer band at the Brillouin-zone center, which is thought to be responsible
      for the superconductivity in 3D GICs, in addition to a large pi* Fermi surface at
      the zone boundary. The present success in fabricating Ca-intercalated bilayer
      graphene would open a promising route to search for other 2D superconductors as
      well as to explore its application in devices.

PMID- 23139408
TI  - Redefining functional MYCN gene signatures in neuroblastoma.

PMID- 23139409
TI  - MAPK phosphatase-1 is required for regulatory natural autoantibody-mediated
      inhibition of TLR responses.
AB  - Naturally arising IgM antibodies, which recognize neo-determinants on apoptotic
      cell (AC) membranes, are present from birth and can be further induced by AC
      challenge. Such naturally arising IgM antibodies can suppress proinflammatory
      responses to purified agonists for Toll-like receptors (TLRs), as well as block
      the induction of IgG immune complex-induced in vitro and in vivo pathogenic
      responses. To investigate the responsible mechanisms, we studied the regulatory
      effects of IgM anti-AC antibody on responses in bone marrow-derived dendritic
      cells mediated by a range of different TLRs and found that addition of IgM anti
      AC inhibited the activation of the primary MAPKs: ERK1/2, JNK, and particularly
      p38. This was dependent on the recruitment of either C1q or mannose-binding
      lectin, which are both early complement factors that tag ACs for innate immune
      recognition. Strikingly, MAPK inhibition of responses to TLR agonists, and to
      lupus IgG autoantibody-chromatin immune complexes, was found to correlate with,
      and had an absolute requirement for, the induction and nuclear localization of
      MAPK phosphatase-1, a factor known to mediate glucocorticoid suppression of
      immune responses. Further experiments showed that natural IgM antibodies in serum
      exhibited the same inhibitory properties. These studies elucidate a novel
      homeostatic pathway by which natural antibodies, which are products of the
      adaptive immune system, can directly blunt inflammatory responses by recruitment
      and coordination of a primitive regulatory pathway of the innate immune system.

PMID- 23139410
TI  - Unique motifs and hydrophobic interactions shape the binding of modified DNA
      ligands to protein targets.
AB  - Selection of aptamers from nucleic acid libraries by in vitro evolution
      represents a powerful method of identifying high-affinity ligands for a broad
      range of molecular targets. Nevertheless, a sizeable fraction of proteins remain
      difficult targets due to inherently limited chemical diversity of nucleic acids.
      We have exploited synthetic nucleotide modifications that confer protein-like
      diversity on a nucleic acid scaffold, resulting in a new generation of binding
      reagents called SOMAmers (Slow Off-rate Modified Aptamers). Here we report a
      unique crystal structure of a SOMAmer bound to its target, platelet-derived
      growth factor B (PDGF-BB). The SOMAmer folds into a compact structure and
      exhibits a hydrophobic binding surface that mimics the interface between PDGF-BB
      and its receptor, contrasting sharply with mainly polar interactions seen in
      traditional protein-binding aptamers. The modified nucleotides circumvent the
      intrinsic diversity constraints of natural nucleic acids, thereby greatly
      expanding the structural vocabulary of nucleic acid ligands and considerably
      broadening the range of accessible protein targets.

PMID- 23139411
TI  - Influence of social networking websites on medical school and residency selection
      process.
AB  - BACKGROUND: Social networking (SN) has become ubiquitous in modern culture. The
      potential consequences of revealing personal information through SN websites are
      not fully understood. OBJECTIVE: To assess familiarity with, usage of, and
      attitudes towards, SN websites by admissions offices at US medical schools and
      residency programmes. METHODS: A 26-question survey was distributed in autumn
      2009 to 130 US medical school admissions officers and 4926 residency programme
      directors accredited by the Accreditation Council for Graduate Medical Education.
      RESULTS: A total of 600 surveys were completed, with 46 (8%) respondents who self
      identified as reviewing only medical school applications, 511 (85%) who reported
      reviewing residency programme applications and 43 (7%) who reported reviewing
      both. 90/600 (15%) medical schools or programmes maintain profiles on SN websites
      and 381/600 (64%) respondents reported being somewhat or very familiar with
      searching individual profiles on SN websites. While a minority of medical schools
      and residency programmes routinely use SN websites in the selection process
      (53/600; 9%), more than half of respondents felt that unprofessional information
      on applicants' SN websites could compromise their admission into medical school
      or residency (315/600; 53%). CONCLUSIONS: SN websites will affect selection of
      medical students and residents. Formal guidelines for professional behaviour on
      SN websites might help applicants avoid unforeseen bias in the selection process.

PMID- 23139412
TI  - A universally conserved ATPase regulates the oxidative stress response in
      Escherichia coli.
AB  - YchF is an evolutionarily conserved ATPase of unknown function. In humans, the
      YchF homologue hOla1 appears to influence cell proliferation and was found to be
      up-regulated in many tumors. A possible involvement in regulating the oxidative
      stress response was also suggested, but details on the underlying mechanism are
      lacking. For gaining insight into YchF function, we used Escherichia coli as a
      model organism and found that YchF overexpression resulted in H(2)O(2)
      hypersensitivity. This was not caused by transcriptional or translational down
      regulation of H(2)O(2)-scavenging enzymes. Instead, we observed YchF-dependent
      inhibition of catalase activity and a direct interaction with the major E. coli
      catalase KatG. KatG inhibition was dependent on the ATPase activity of YchF and
      was regulated by post-translational modifications, most likely including an
      H(2)O(2)-dependent dephosphorylation. We furthermore showed that YchF expression
      is repressed by the transcription factor OxyR and further post-translationally
      modified in response to H(2)O(2). In summary, our data show that YchF functions
      as a novel negative regulator of the oxidative stress response in E. coli.
      Considering the available data on hOla1, YchF/Ola1 most likely execute similar
      functions in bacteria and humans, and their up-regulation inhibits the ability of
      the cells to scavenge damaging reactive oxygen species.

PMID- 23139413
TI  - Long range effect of mutations on specific conformational changes in the
      extracellular loop 2 of angiotensin II type 1 receptor.
AB  - The topology of the second extracellular loop (ECL2) and its interaction with
      ligands is unique in each G protein-coupled receptor. When the orthosteric ligand
      pocket located in the transmembrane (TM) domain is occupied, ligand-specific
      conformational changes occur in the ECL2. In more than 90% of G protein-coupled
      receptors, ECL2 is tethered to the third TM helix via a disulfide bond.
      Therefore, understanding the extent to which the TM domain and ECL2 conformations
      are coupled is useful. To investigate this, we examined conformational changes in
      ECL2 of the angiotensin II type 1 receptor (AT1R) by introducing mutations in
      distant sites that alter the activation state equilibrium of the AT1R.
      Differential accessibility of reporter cysteines introduced at four conformation
      sensitive sites in ECL2 of these mutants was measured. Binding of the agonist
      angiotensin II (AngII) and inverse agonist losartan in wild-type AT1R changed the
      accessibility of reporter cysteines, and the pattern was consistent with ligand
      specific "lid" conformations of ECL2. Without agonist stimulation, the ECL2 in
      the gain of function mutant N111G assumed a lid conformation similar to AngII
      bound wild-type AT1R. In the presence of inverse agonists, the conformation of
      ECL2 in the N111G mutant was similar to the inactive state of wild-type AT1R. In
      contrast, AngII did not induce a lid conformation in ECL2 in the loss of function
      D281A mutant, which is consistent with the reduced AngII binding affinity in this
      mutant. However, a lid conformation was induced by [Sar(1),Gln(2),Ile(8)] AngII,
      a specific analog that binds to the D281A mutant with better affinity than AngII.
      These results provide evidence for the emerging paradigm of domain coupling
      facilitated by long range interactions at distant sites on the same receptor.

PMID- 23139415
TI  - Identification of a tetrahydroquinoline analog as a pharmacological inhibitor of
      the cAMP-binding protein Epac.
AB  - The cAMP-binding protein Epac is a therapeutic target for the treatment of
      various diseases such as cardiac hypertrophy and tumor invasion. This points out
      the importance to develop Epac inhibitors to better understand the involvement of
      these cAMP sensors in physiology and pathophysiology. Here, we have developed a
      functional fluorescence-based high-throughput assay with a Z' value around 0.7
      for screening Epac-specific antagonists. We identified an Epac1 inhibitor
      compound named CE3F4 that blocked Epac1 guanine nucleotide exchange activity
      toward its effector Rap1 both in cell-free systems and in intact cells. CE3F4 is
      a tetrahydroquinoline analog that fails to influence protein kinase A holoenzyme
      activity. CE3F4 inhibited neither the interaction of Rap1 with Epac1 nor directly
      the GDP exchange on Rap1. The kinetics of inhibition by CE3F4 indicated that this
      compound did not compete for binding of agonists to Epac1 and suggested an
      uncompetitive inhibition mechanism with respect to Epac1 agonists. A structure
      activity study showed that the formyl group on position 1 and the bromine atom on
      position 5 of the tetrahydroquinoline skeleton were important for CE3F4 to exert
      its inhibitory activity. Finally, CE3F4 inhibited Rap1 activation in living
      cultured cells, following Epac activation by either 8-(4-chlorophenylthio)-2'-O
      methyl-cAMP, an Epac-selective agonist, or isoprenaline, a non-selective beta
      adrenergic receptor agonist. Our study shows that CE3F4 and related compounds may
      serve as a basis for the development of new therapeutic drugs.

PMID- 23139414
TI  - The specificity protein factor Sp1 mediates transcriptional regulation of P2X7
      receptors in the nervous system.
AB  - P2X7 receptors are involved not only in physiological functions but also in
      pathological brain processes. Although an increasing number of findings indicate
      that altered receptor expression has a causative role in neurodegenerative
      diseases and cancer, little is known about how expression of P2rx7 gene is
      controlled. Here we reported the first molecular and functional evidence that
      Specificity protein 1 (Sp1) transcription factor plays a pivotal role in the
      transcriptional regulation of P2X7 receptor. We delimited a minimal region in the
      murine P2rx7 promoter containing four SP1 sites, two of them being highly
      conserved in mammals. The functionality of these SP1 sites was confirmed by site
      directed mutagenesis and Sp1 overexpression/down-regulation in neuroblastoma
      cells. Inhibition of Sp1-mediated transcriptional activation by mithramycin A
      reduced endogenous P2X7 receptor levels in primary cultures of cortical neurons
      and astrocytes. Using P2rx7-EGFP transgenic mice that express enhanced green
      fluorescent protein under the control of P2rx7 promoter, we found a high
      correlation between reporter expression and Sp1 levels in the brain,
      demonstrating that Sp1 is a key element in the transcriptional regulation of P2X7
      receptor in the nervous system. Finally, we found that Sp1 mediates P2X7 receptor
      up-regulation in neuroblastoma cells cultured in the absence of serum, a
      condition that enhances chromatin accessibility and facilitates the exposure of
      SP1 binding sites.

PMID- 23139416
TI  - Genetic analysis of the Hox hydrogenase in the cyanobacterium Synechocystis sp.
      PCC 6803 reveals subunit roles in association, assembly, maturation, and
      function.
AB  - Hydrogenases are metalloenzymes that catalyze 2H(+) + 2e(-) <-> H(2). A
      multisubunit, bidirectional [NiFe]-hydrogenase has been identified and
      characterized in a number of bacteria, including cyanobacteria, where it is
      hypothesized to function as an electron valve, balancing reductant in the cell.
      In cyanobacteria, this Hox hydrogenase consists of five proteins in two
      functional moieties: a hydrogenase moiety (HoxYH) with homology to heterodimeric
      [NiFe]-hydrogenases and a diaphorase moiety (HoxEFU) with homology to NuoEFG of
      respiratory Complex I, linking NAD(P)H <-> NAD(P)(+) as a source/sink for
      electrons. Here, we present an extensive study of Hox hydrogenase in the
      cyanobacterium Synechocystis sp. PCC 6803. We identify the presence of HoxEFUYH,
      HoxFUYH, HoxEFU, HoxFU, and HoxYH subcomplexes as well as association of the
      immature, unprocessed large subunit (HoxH) with other Hox subunits and
      unidentified factors, providing a basis for understanding Hox maturation and
      assembly. The analysis of mutants containing individual and combined hox gene
      deletions in a common parental strain reveals apparent alterations in subunit
      abundance and highlights an essential role for HoxF and HoxU in
      complex/subcomplex association. In addition, analysis of individual and combined
      hox mutant phenotypes in a single strain background provides a clear view of the
      function of each subunit in hydrogenase activity and presents evidence that its
      physiological function is more complicated than previously reported, with no
      outward defects apparent in growth or photosynthesis under various growth
      conditions.

PMID- 23139417
TI  - The phosphocholine-binding pocket on C-reactive protein is necessary for initial
      protection of mice against pneumococcal infection.
AB  - Human C-reactive protein (CRP) protects mice from lethal Streptococcus pneumoniae
      infection when injected into mice within the range of 6 h before to 2 h after the
      administration of pneumococci. Because CRP binds to phosphocholine-containing
      substances and subsequently activates the complement system, it has been proposed
      that the antipneumococcal function of CRP requires the binding of CRP to
      phosphocholine moieties present in pneumococcal cell wall C-polysaccharide. To
      test this proposal experimentally, in this study, we utilized a new CRP mutant
      incapable of binding to phosphocholine. Based on the structure of CRP
      phosphocholine complexes, which showed that Phe(66), Thr(76), and Glu(81) formed
      the phosphocholine-binding pocket, we constructed a CRP mutant F66A/T76Y/E81A in
      which the pocket was blocked by substituting Tyr for Thr(76). When compared with
      wild-type CRP, mutant CRP bound more avidly to phosphoethanolamine and could be
      purified by affinity chromatography using phosphoethanolamine-conjugated
      Sepharose. Mutant CRP did not bind to phosphocholine, C-polysaccharide, or
      pneumococci. Mutant CRP was free in the mouse serum, and its rate of clearance in
      vivo was not faster than that of wild-type CRP. When either 25 MUg or 150 MUg of
      CRP was administered into mice, unlike wild-type CRP, mutant CRP did not protect
      mice from lethal pneumococcal infection. Mice injected with mutant CRP had higher
      mortality rates than mice that received wild-type CRP. Decreased survival was due
      to the increased bacteremia in mice treated with mutant CRP. We conclude that the
      phosphocholine-binding pocket on CRP is necessary for CRP-mediated initial
      protection of mice against lethal pneumococcal infection.

PMID- 23139418
TI  - The stability of the small nucleolar ribonucleoprotein (snoRNP) assembly protein
      Pih1 in Saccharomyces cerevisiae is modulated by its C terminus.
AB  - Pih1 is an unstable protein and a subunit of the R2TP complex that, in yeast
      Saccharomyces cerevisiae, also contains the helicases Rvb1, Rvb2, and the Hsp90
      cofactor Tah1. Pih1 and the R2TP complex are required for the box C/D small
      nucleolar ribonucleoprotein (snoRNP) assembly and ribosomal RNA processing.
      Purified Pih1 tends to aggregate in vitro. Molecular chaperone Hsp90 and its
      cochaperone Tah1 are required for the stability of Pih1 in vivo. We had shown
      earlier that the C terminus of Pih1 destabilizes the protein and that the C
      terminus of Tah1 binds to the Pih1 C terminus to form a stable complex. Here, we
      analyzed the secondary structure of the Pih1 C terminus and identified two
      intrinsically disordered regions and five hydrophobic clusters. Site-directed
      mutagenesis indicated that one predicted intrinsically disordered region IDR2 is
      involved in Tah1 binding, and that the C terminus of Pih1 contains multiple
      destabilization or degron elements. Additionally, the Pih1 N-terminal domain,
      Pih1(1-230), was found to be able to complement the physiological role of full
      length Pih1 at 37  degrees C. Pih1(1-230) as well as a shorter Pih1 N-terminal
      fragment Pih1(1-195) is able to bind Rvb1/Rvb2 heterocomplex. However, the
      sequence between the two disordered regions in Pih1 significantly enhances the
      Pih1 N-terminal domain binding to Rvb1/Rvb2. Based on these data, a model of
      protein-protein interactions within the R2TP complex is proposed.

PMID- 23139419
TI  - Identification of STAT2 serine 287 as a novel regulatory phosphorylation site in
      type I interferon-induced cellular responses.
AB  - STAT2 is a positive modulator of the transcriptional response to type I
      interferons (IFNs). STAT2 acquires transcriptional function by becoming tyrosine
      phosphorylated and imported to the nucleus following type I IFN receptor
      activation. Although most STAT proteins become dually phosphorylated on specific
      tyrosine and serine residues to acquire full transcriptional activity, no serine
      phosphorylation site in STAT2 has been reported. To find novel phosphorylation
      sites, mass spectrometry of immunoprecipitated STAT2 was used to identify several
      phosphorylated residues. Of these, substitution of serine 287 with alanine
      (S287A) generated a gain-of-function mutant that enhanced the biological effects
      of IFN-alpha. S287A-STAT2 increased cell growth inhibition, prolonged protection
      against vesicular stomatitis virus infection and enhanced transcriptional
      responses following exposure of cells to IFN-alpha. In contrast, a phosphomimetic
      STAT2 mutant (S287D) produced a loss-of-function protein that weakly activated
      IFN-induced ISGs. Our mechanistic studies suggest that S287A-STAT2 likely
      mediates its gain-of-function effects by prolonging STAT2/STAT1 dimer activation
      and retaining it in transcriptionally active complexes with chromatin.
      Altogether, we have uncovered that in response to type I IFN, STAT2 is serine
      phosphorylated in the coiled-coil domain that when phosphorylated can negatively
      regulate the biological activities of type I IFNs.

PMID- 23139420
TI  - Integrated redox sensor and effector functions for tetrahydrobiopterin- and
      glutathionylation-dependent endothelial nitric-oxide synthase uncoupling.
AB  - Endothelial nitric-oxide synthase (eNOS) is a critical regulator of vascular
      homeostasis by generation of NO that is dependent on the cofactor
      tetrahydrobiopterin (BH4). When BH4 availability is limiting, eNOS becomes
      "uncoupled," resulting in superoxide production in place of NO. Recent evidence
      suggests that eNOS uncoupling can also be induced by S-glutathionylation,
      although the functional relationships between BH4 and S-glutathionylation remain
      unknown. To address a possible role for BH4 in S-glutathionylation-induced eNOS
      uncoupling, we expressed either WT or mutant eNOS rendered resistant to S
      glutathionylation in cells with Tet-regulated expression of human GTP
      cyclohydrolase I to regulate intracellular BH4 availability. We reveal that S
      glutathionylation of eNOS, by exposure to either 1,3-bis(2-chloroethyl)-1
      nitrosourea (BCNU) or glutathione reductase-specific siRNA, results in diminished
      NO production and elevated eNOS-derived superoxide production, along with a
      concomitant reduction in BH4 levels and BH4:7,8-dihydrobiopterin ratio. In eNOS
      uncoupling induced by BH4 deficiency, BCNU exposure further exacerbates
      superoxide production, BH4 oxidation, and eNOS activity. Following mutation of
      C908S, BCNU-induced eNOS uncoupling and BH4 oxidation are abolished, whereas
      uncoupling induced by BH4 deficiency was preserved. Furthermore, BH4 deficiency
      alone is alone sufficient to reduce intracellular GSH:GSSG ratio and cause eNOS S
      glutathionylation. These data provide the first evidence that BH4 deficiency- and
      S-glutathionylation-induced mechanisms of eNOS uncoupling, although
      mechanistically distinct, are functionally related. We propose that uncoupling of
      eNOS by S-glutathionylation- or by BH4-dependent mechanisms exemplifies eNOS as
      an integrated redox "hub" linking upstream redox-sensitive effects of BH4 and
      glutathione with redox-dependent targets and pathways that lie downstream of
      eNOS.

PMID- 23139421
TI  - Exploring the unique N-glycome of the opportunistic human pathogen Acanthamoeba.
AB  - Glycans play key roles in host-pathogen interactions; thus, knowing the N
      glycomic repertoire of a pathogen can be helpful in deciphering its methods of
      establishing and sustaining a disease. Therefore, we sought to elucidate the
      glycomic potential of the facultative amoebal parasite Acanthamoeba. This is the
      first study of its asparagine-linked glycans, for which we applied biochemical
      tools and various approaches of mass spectrometry. An initial glycomic screen of
      eight strains from five genotypes of this human pathogen suggested, in addition
      to the common eukaryotic oligomannose structures, the presence of pentose and
      deoxyhexose residues on their N-glycans. A more detailed analysis was performed
      on the N-glycans of a genotype T11 strain (4RE); fractionation by HPLC and tandem
      mass spectrometric analyses indicated the presence of a novel mannosylfucosyl
      modification of the reducing terminal core as well as phosphorylation of mannose
      residues, methylation of hexose and various forms of pentosylation. The largest N
      glycan in the 4RE strain contained two N-acetylhexosamine, thirteen hexose, one
      fucose, one methyl, and two pentose residues; however, in this and most other
      strains analyzed, glycans with compositions of Hex(8-9)HexNAc(2)Pnt(0-1) tended
      to dominate in terms of abundance. Although no correlation between pathogenicity
      and N-glycan structure can be proposed, highly unusual structures in this
      facultative parasite can be found which are potential virulence factors or
      therapeutic targets.

PMID- 23139422
TI  - The plasma membrane sialidase NEU3 regulates the malignancy of renal carcinoma
      cells by controlling beta1 integrin internalization and recycling.
AB  - The human plasma membrane sialidase NEU3 is a key enzyme in the catabolism of
      membrane gangliosides, is crucial in the regulation of cell surface processes,
      and has been demonstrated to be significantly up-regulated in renal cell
      carcinomas (RCCs). In this report, we show that NEU3 regulates beta1 integrin
      trafficking in RCC cells by controlling beta1 integrin recycling to the plasma
      membrane and controlling activation of the epidermal growth factor receptor
      (EGFR) and focal adhesion kinase (FAK)/protein kinase B (AKT) signaling. NEU3
      silencing in RCC cells increased the membrane ganglioside content, in particular
      the GD1a content, and changed the expression of key regulators of the integrin
      recycling pathway. In addition, NEU3 silencing up-regulated the Ras-related
      protein RAB25, which directs internalized integrins to lysosomes, and down
      regulated the chloride intracellular channel protein 3 (CLIC3), which induces the
      recycling of internalized integrins to the plasma membrane. In this manner, NEU3
      silencing enhanced the caveolar endocytosis of beta1 integrin, blocked its
      recycling and reduced its levels at the plasma membrane, and, consequently,
      inhibited EGFR and FAK/AKT. These events had the following effects on the
      behavior of RCC cells: they (a) decreased drug resistance mediated by the block
      of autophagy and the induction of apoptosis; (b) decreased metastatic potential
      mediated by down-regulation of the metalloproteinases MMP1 and MMP7; and (c)
      decreased adhesion to collagen and fibronectin. Therefore, our data identify NEU3
      as a key regulator of the beta1 integrin-recycling pathway and FAK/AKT signaling
      and demonstrate its crucial role in RCC malignancy.

PMID- 23139423
TI  - Biosynthesis of the fungal cell wall polysaccharide galactomannan requires
      intraluminal GDP-mannose.
AB  - Fungal cell walls frequently contain a polymer of mannose and galactose called
      galactomannan. In the pathogenic filamentous fungus Aspergillus fumigatus, this
      polysaccharide is made of a linear mannan backbone with side chains of
      galactofuran and is anchored to the plasma membrane via a
      glycosylphosphatidylinositol or is covalently linked to the cell wall. To date,
      the biosynthesis and significance of this polysaccharide are unknown. The present
      data demonstrate that deletion of the Golgi UDP-galactofuranose transporter GlfB
      or the GDP-mannose transporter GmtA leads to the absence of galactofuran or
      galactomannan, respectively. This indicates that the biosynthesis of
      galactomannan probably occurs in the lumen of the Golgi apparatus and thus
      contrasts with the biosynthesis of other fungal cell wall polysaccharides studied
      to date that takes place at the plasma membrane. Transglycosylation of
      galactomannan from the membrane to the cell wall is hypothesized because both the
      cell wall-bound and membrane-bound polysaccharide forms are affected in the
      generated mutants. Considering the severe growth defect of the A. fumigatus GmtA
      deficient mutant, proving this paradigm might provide new targets for antifungal
      therapy.

PMID- 23139424
TI  - Accuracy of physical therapists' early predictions of upper-limb function in
      hospital stroke units: the EPOS Study.
AB  - BACKGROUND: Early prediction of outcome after stroke is becoming increasingly
      important, as most patients are discharged from hospital stroke units within
      several days after stroke. OBJECTIVES: The primary purposes of this study were:
      (1) to determine the accuracy of physical therapists' predictions at hospital
      stroke units regarding upper-limb (UL) function, (2) to develop a computational
      prediction model (CPM), and (3) to compare the accuracy of physical therapists'
      and the CPM's predictions. Secondary objectives were to explore the impact of
      timing on the accuracy of the physical therapists' and CPM's predictions and to
      investigate the direction of the difference between predicted and observed
      outcomes. Finally, this study investigated whether the accuracy of physical
      therapists' predictions was affected by their experience in stroke
      rehabilitation. DESIGN: A prospective cohort study was conducted. METHODS:
      Physical therapists made predictions at 2 time points-within 72 hours after
      stroke onset (T(72h)) and at discharge from the hospital stroke unit (Tdischarge)
      about UL function after 6 months in 3 categories, derived from the action
      research arm test. At the same time, clinical variables were measured to derive a
      CPM. The accuracy of the physical therapists' and CPM's predictions was evaluated
      by calculating Spearman rank correlation coefficients (r(s)) between predicted
      and observed outcomes. RESULTS: One hundred thirty-one patients and 20 physical
      therapists participated in the study. For the T(72h) assessment, the rs value
      between predicted and observed outcomes was .63 for the physical therapists'
      predictions and .75 for the CPM's predictions. For the Tdischarge assessment, the
      rs value for the physical therapists' predictions improved to .75, and the rs
      value for the CPM's predictions improved slightly to .76. LIMITATIONS: Physical
      therapists administered a test battery every 3 days, which may have enhanced the
      accuracy of prediction. CONCLUSIONS: The accuracy of the physical therapists'
      predictions at T(72h) was lower than that of the CPM's predictions. At
      Tdischarge, the physical therapists' and CPM's predictions are about equally
      accurate.

PMID- 23139425
TI  - Reliability and responsiveness of the gross motor function measure-88 in children
      with cerebral palsy.
AB  - BACKGROUND: The Gross Motor Function Measure (GMFM-88) is commonly used in the
      evaluation of gross motor function in children with cerebral palsy (CP). The
      relative reliability of GMFM-88 has been assessed in children with CP. However,
      little information is available regarding the absolute reliability or
      responsiveness of GMFM-88. OBJECTIVE: The purpose of this study was to determine
      the absolute and relative reliability and the responsiveness of the GMFM-88 in
      evaluating gross motor function in children with CP. DESIGN: A clinical
      measurement design was used. METHODS: Ten raters scored the GMFM-88 in 84
      children (mean age=3.7 years, SD=1.9, range=10 months to 9 years 9 months) from
      video records across all Gross Motor Function Classification System (GMFCS)
      levels to establish interrater reliability. Two raters participated to assess
      intrarater reliability. Responsiveness was determined from 3 additional
      assessments after the baseline assessment. The interrater and intrarater
      intraclass correlation coefficients (ICCs) with 95% confidence intervals,
      standard error of measurement (SEM), smallest real difference (SRD), effect size
      (ES), and standardized response mean (SRM) were calculated. RESULTS: The relative
      reliability of the GMFM was excellent (ICCs=.952-1.000). The SEM and SRD for
      total score of the GMFM were acceptable (1.60 and 3.14, respectively).
      Additionally, the ES and SRM of the dimension goal scores increased gradually in
      the 3 follow-up assessments (GMFCS levels I and II: ES=0.5, 0.6, and 0.8 and
      SRM=1.3, 1.8, and 2.0; GMFCS levels III-V: ES=0.4, 0.7, and 0.9 and SRM=1.5, 1.7,
      and 2.0). LIMITATIONS: Children over 10 years of age with CP were not included in
      this study, so the results should not be generalized to all children with CP.
      CONCLUSIONS: Both the reliability and the responsiveness of the GMFM-88 are
      reasonable for measuring gross motor function in children with CP.

PMID- 23139426
TI  - What characterizes people who have an unclear classification using a treatment
      based classification algorithm for low back pain? A cross-sectional study.
AB  - BACKGROUND: A treatment-based classification algorithm for low back pain (LBP)
      was created to help clinicians select treatments to which people are most likely
      to respond. To allow the algorithm to classify all people with LBP, additional
      criteria can help therapists make decisions for people who do not clearly fit
      into a subgroup (ie, unclear classifications). Recent studies indicated that
      classifications are unclear for approximately 34% of people with LBP. OBJECTIVE:
      To guide improvements in the algorithm, it is imperative to determine whether
      people with unclear classifications are different from those with clear
      classifications. DESIGN: This study was a secondary analysis of data from 3
      previous studies investigating the algorithm. METHODS: Baseline data from 529
      people who had LBP were used (3 discrete cohorts). The primary outcome was type
      of classification, that is, clear or unclear. Univariate logistic regression was
      used to determine which participant variables were related to having an unclear
      classification. RESULTS: People with unclear classifications had greater odds of
      being older (odds ratio [OR]=1.01, 95% confidence interval [CI]=1.003-1.033),
      having a longer duration of LBP (OR=1.001, 95% CI=1.000-1.001), having had a
      previous episode(s) of LBP (OR=1.61, 95% CI=1.04-2.49), having fewer fear
      avoidance beliefs related to both work (OR=0.98, 95% CI=0.96-0.99) and physical
      activity (OR=0.98, 95% CI=0.96-0.996), and having less LBP-related disability
      (OR=0.98, 95% CI=0.96-0.99) than people with clear classifications. LIMITATIONS:
      Studies from which participant data were drawn had different inclusion criteria
      and clinical settings. CONCLUSIONS: People with unclear classifications appeared
      to be less affected by LBP (less disability and fewer fear avoidance beliefs),
      despite typically having a longer duration of LBP. Future studies should
      investigate whether modifying the algorithm to exclude such people or provide
      them with different interventions improves outcomes.

PMID- 23139428
TI  - The therapeutic alliance between clinicians and patients predicts outcome in
      chronic low back pain.
AB  - BACKGROUND: The impact of the relationship (therapeutic alliance) between
      patients and physical therapists on treatment outcome in the rehabilitation of
      patients with chronic low back pain (LBP) has not been previously investigated.
      OBJECTIVE: The purpose of this study was to investigate whether the therapeutic
      alliance between physical therapists and patients with chronic LBP predicts
      clinical outcomes. DESIGN: This was a retrospective observational study nested
      within a randomized controlled trial. METHODS: One hundred eighty-two patients
      with chronic LBP who volunteered for a randomized controlled trial that compared
      the efficacy of exercises and spinal manipulative therapy rated their alliance
      with physical therapists by completing the Working Alliance Inventory at the
      second treatment session. The primary outcomes of function, global perceived
      effect of treatment, pain, and disability were assessed before and after 8 weeks
      of treatment. Linear regression models were used to investigate whether the
      alliance was a predictor of outcome or moderated the effect of treatment.
      RESULTS: The therapeutic alliance was consistently a predictor of outcome for all
      the measures of treatment outcome. The therapeutic alliance moderated the effect
      of treatment on global perceived effect for 2 of 3 treatment contrasts (general
      exercise versus motor control exercise, spinal manipulative therapy versus motor
      control exercise). There was no treatment effect modification when outcome was
      measured with function, pain, and disability measures. LIMITATIONS: Therapeutic
      alliance was measured at the second treatment session, which might have biased
      the interaction during initial stages of treatment. Data analysis was restricted
      to primary outcomes at 8 weeks. CONCLUSIONS: Positive therapeutic alliance
      ratings between physical therapists and patients are associated with improvements
      of outcomes in LBP. Future research should investigate the factors explaining
      this relationship and the impact of training interventions aimed at optimizing
      the alliance.

PMID- 23139427
TI  - Effect of externally cued training on dynamic stability control during the sit-to
      stand task in people with Parkinson disease.
AB  - BACKGROUND: Previous studies have shown that people with Parkinson disease (PD)
      have difficulty performing the sit-to-stand task because of mobility and
      stability-related impairments. Despite its importance, literature on the
      quantification of dynamic stability control in people with PD during this task is
      limited. OBJECTIVE: The study objective was to examine differences in dynamic
      stability control between people with PD and people who were healthy and the
      extent to which externally cued training could improve such control during the
      sit-to-stand task in people with PD. DESIGN: This was a quasi-experimental
      controlled trial. METHODS: The performance of 21 people with PD was compared with
      that of 12 older adults who dwelled in the community. People with PD were
      randomly assigned to 2 groups: a group that did not receive training and a group
      that received audiovisually cued training (3 times per week for 4 weeks) for
      speeding up performance on the sit-to-stand task. Outcome measures recorded at
      baseline and after 4 weeks included center-of-mass position, center-of-mass
      velocity, and stability against either backward or forward balance loss (backward
      or forward stability) at seat-off and movement termination. RESULTS: Compared
      with people who were healthy, people with PD had greater backward stability
      resulting from a more anterior center-of-mass position at seat-off. This feature,
      combined with decreased forward stability at movement termination, increased
      their risk of forward balance loss at movement termination. After training,
      people with PD achieved greater backward stability through increased forward
      center-of-mass velocity at seat-off and reduced the likelihood of forward balance
      loss at movement termination through a posterior shift in the center-of-mass
      position. LIMITATIONS: The study applied stability limits derived from adults who
      were healthy to people with PD, and the suggested impact on the risk of balance
      loss and falling is based on these theoretical stability limits. CONCLUSIONS: For
      people with PD, postural stability against backward balance loss at task
      initiation was increased at the expense of possible forward balance loss at task
      termination. Task-specific training with preparatory audiovisual cues resulted in
      improved overall dynamic stability against both forward and backward balance
      loss.

PMID- 23139429
TI  - Inhibition of meningitis-associated neutrophil apoptosis by TNF-alpha depends on
      functional PI3-kinase in monocytes.
AB  - In bacterial meningitis, neutrophils cope with bacterial infection but also lead
      to tissue damage. The balance of beneficial and harmful effects may depend on the
      lifespan of the neutrophils in the CNS. Here, we show that CSF of patients with
      meningococcal meningitis contains a neutrophil apoptosis-inhibiting capacity that
      correlates with TNF-alpha content. In vitro experiments show that Neisseria
      meningitidis as well as LPS derived from these bacteria regulated neutrophil
      apoptosis mainly by stimulating TNF-alpha production in monocytes. Whereas LPS
      induced PI3K-dependent survival signals in monocytes are critical for neutrophil
      survival, PI3K signaling in granulocytes did not contribute to the increased
      lifespan of neutrophils. We conclude that LPS-driven PI3K signaling in monocytes
      regulates neutrophil apoptosis and thereby, may be crucial in the initiation of
      secondary brain damage in bacterial meningitis.

PMID- 23139430
TI  - Fenretinide inhibited de novo ceramide synthesis and proinflammatory cytokines
      induced by Aggregatibacter actinomycetemcomitans.
AB  - Ceramides play an essential role in modulating immune signaling pathways and
      proinflammatory cytokine production in response to infectious pathogens, stress
      stimuli, or chemotherapeutic drugs. In this study, we demonstrated that
      Aggregatibacter actinomycetemcomitans, the pathogen for aggressive periodontitis,
      induced de novo synthesis of ceramide in Raw 264.7 cells. In addition, we
      identified that fenretinide, a synthetic retinoid, suppressed the de novo
      synthesis of ceramide induced by A. actinomycetemcomitans. Moreover, fenretinide
      attenuated interleukin (IL)-1beta, IL-6, and cyclooxygenase-2 mRNA expression
      induced by A. actinomycetemcomitans. Fenretinide also decreased IL-1beta, IL-6,
      and prostaglandin E2 proinflammatory cytokine levels in Raw 264.7 cells induced
      by A. actinomycetemcomitans. However, fenretinide had no significant effects on
      tumor necrosis factor alpha mRNA or protein levels. Furthermore, we showed that
      fenretinide inhibited the janus kinase-signal transducer and activator of
      transcription, phosphatidylinositol 3-kinase-Akt, protein kinase C, and nuclear
      factor-kappaB signaling pathways, whereas fenretinide up-regulated the mitogen
      activated protein kinase signaling pathways after bacterial stimulation. This
      study emphasizes the de novo ceramide synthesis pathway in response to bacterial
      stimulation and demonstrates the anti-inflammatory role of fenretinide in the
      bacteria-induced immune response.

PMID- 23139432
TI  - Synthesis and Biological Evaluation of Novel 3'-Difluorovinyl Taxoids.
AB  - A series of 3'-difluorovinyl taxoids with C10 modifications, as well as those
      with C2 and C10 modifications, were strategically designed to block the
      metabolism by cytochrome P-450 3A4 enzyme and synthesized. These novel
      difluorovinyl taxoids were evaluated for their cytotoxicity against drug
      sensitive human breast (MCF7), multidrug-resistant (MDR) human ovarian (NCI/ADR),
      human colon (HT-29) and human pancreatic (PANC-1) cancer cell lines. 3'
      Difluorovinyl taxoids exhibit several to 16 times better activity against MCF7,
      HT-29 and PANC-1 cell lines and up to three orders of magnitude higher potency
      against NCI/ADR cell line as compared to paclitaxel. Structure-activity
      relationship study shows the critical importance of the C2 modifications on the
      activity against MDR cancer cell line, while the C10 modifications have a rather
      minor effect on the potency with some exceptions. The effect of the C2
      modifications on potency against MCF7 cell line increases in the following order:
      H < F < Cl <N(3). Among the twenty five 3'-difluorovinyl taxoids evaluated, eight
      taxoids exhibited less than 100 pM IC(50) values against MCF7 cell line.
      Difluorovinyl taxoids induced GTP-independent tubulin polymerization much faster
      than paclitaxel. Then, the resulting microtubules were stable to Ca(2+)-induced
      depolymerization, indicating strong stabilization of microtubules. Molecular
      modeling study indicated that a difluorovinyl taxoid binds to beta-tubulin in a
      manner that is consistent with the REDOR-Taxol structure. The difluorovinyl group
      appears to mimic the isobutenyl group to some extent, but with very different
      electronic property, which may account for the unique activities of difluorovinyl
      taxoids.

PMID- 23139434
TI  - Tandem chain extension-Mannich reaction: an approach to beta-proline derivatives.
AB  - A zinc carbenoid-initiated chain extension reaction provides access to an
      organometallic intermediate, which can be used to capture activated imines.
      Deprotection of the nitrogen and reduction provides access to racemic derivatives
      of beta-proline. The relative stereochemistry of the beta-proline can be
      controlled through use of different activating groups on the imine nitrogen.

PMID- 23139435
TI  - Acid and base catalyzed Davis-Beirut reaction: experimental and theoretical
      mechanistic studies and synthesis of novel 3-amino-2H-indazoles.
AB  - The Davis-Beirut reaction, which provides an efficient synthesis of 2H-indazoles
      and, subsequently, indazolones, is shown to proceed rapidly from o
      nitrosobenzaldehyde and primary amines under both acid or base catalysis.
      Experimental and theoretical evidence in support of a reaction mechanism is
      provided in which o-nitrosobenzylidine imine is a pivotal intermediate in this
      N,N-bond forming heterocyclization reaction. The Davis-Beirut reaction is also
      shown to effectively synthesize a number of novel 3-amino-2H-indazole
      derivatives.

PMID- 23139433
TI  - Prospective Memory in a Language-Trained Chimpanzee (Pan troglodytes).
AB  - Prospective memory involves the encoding, retention, and implementation of an
      intended future action. Although humans show many forms of prospective memory,
      less is known about the future oriented processes of nonhuman animals, or their
      ability to use prospective memory. In this experiment, a chimpanzee named Panzee,
      who had learned to associate geometric forms called lexigrams with real-world
      referents, was given a prospective memory test. Panzee selected between two foods
      the one she wanted to receive more immediately. That food was scattered in an
      outdoor yard where she could forage for it. Also outdoors were lexigram tokens,
      one of which represented the food item that remained indoors throughout a 30
      minute period, and that could be obtained if Panzee brought in the token that
      matched that food item. After foraging for the selected food item, Panzee
      consistently remembered to retrieve and return the correct token when food was
      available indoors, whereas on control trials involving no indoor food she rarely
      returned a token. This indicated that Panzee encoded information relevant to the
      future action of token retrieval after extended delays for one type of food, even
      when a more immediately preferred food was available.

PMID- 23139436
TI  - The Caregiver as Gatekeeper for Accessing Health Care for Children in Foster
      Care: A Qualitative Study of Kinship and Unrelated Caregivers.
AB  - The objective of this qualitative study was to examine issues that unrelated and
      kinship foster caregivers in Los Angeles, CA, have in seeking help and accessing
      and using health care for children in foster care. There were four themes
      identified for all caregivers: (1) "Doing Our Best" (caregivers advocated
      persistently and creatively for health care); (2) "Support from Others Helped"
      (caregivers relied on caseworkers, organizations, and their social network); (3)
      "Child has Complicated, Serious, Chronic Health Problems" (caregivers had
      difficulty securing specialty services and with Medicaid insurance to meet health
      care needs); and (4) "Caregiver Competence in Meeting Health Needs" (caregivers
      noted their ability to attend health appointments and understand instructions).
      An additional theme of "Differences between Unrelated and Kinship Foster
      Caregivers" highlighted more difficulties among kinship caregivers in finding and
      using primary health care services and more financial stress, whereas unrelated
      caregivers were less satisfied with child welfare caseworker help. Despite wide
      ranging stressors and serious frustrations with the child welfare and health care
      systems, caregivers emerged as powerful drivers of health care for foster
      children. National adoption of a medical home model would ameliorate some of the
      access barriers identified by foster caregivers in this study.

PMID- 23139437
TI  - Temperament and Common Disruptive Behavior Problems in Preschool.
AB  - The study evaluated trait associations with common Disruptive Behavior Disorders
      (DBD), Oppositional Defiant Disorder (ODD) and Attention-Deficit/Hyperactivity
      Disorder (ADHD), during an understudied developmental period: Preschool.
      Participants were 109 children ages 3 to 6 and their families. DBD symptoms were
      available via parent and teacher/caregiver report on the Disruptive Behavior
      Rating Scale. Traits were measured using observational coding paradigms, and
      parent and examiner report on the Child Behavior Questionnaire and the California
      Q-Sort. The DBD groups exhibited significantly higher negative affect, higher
      surgency, and lower effortful control. Negative affect was associated with most
      DBD symptom domains; surgency and reactive control were associated with
      hyperactivity-impulsivity; and effortful control was associated with ADHD and
      inattention. Interactive effects between effortful control and negative affect
      and curvilinear associations of reactive control with DBD symptoms were evident.
      Temperament trait associations with DBD during preschool are similar to those
      seen during middle childhood. Extreme levels of temperament traits are associated
      with DBD as early as preschool.

PMID- 23139438
TI  - Examining the Pathways between Gratitude and Self-Rated Physical Health across
      Adulthood.
AB  - The current study examined whether dispositional gratitude predicts physical
      health among adults, and if so, whether this relationship occurs because grateful
      individuals lead healthier lives, either psychologically or physically.
      Specifically, we examined whether psychological health, healthy activities, and
      willingness to seek help for health concerns mediated the link between gratitude
      and self-reported physical health, as well as if these mediational pathways are
      moderated by age, in a broad sample of Swiss adults (N = 962, M(age) = 52 years,
      age range: 19 to 84). Dispositional gratitude correlated positively with self
      reported physical health, and this link was mediated by psychological health,
      healthy activities, and willingness to seek help for health concerns. However,
      the indirect effects for psychological health and healthy activities were
      stronger for older than younger adults. In other words, the mechanisms explaining
      why gratitude predicts health appear to differ across adulthood.

PMID- 23139440
TI  - One-step Melt Synthesis of Water Soluble, Photoluminescent, Surface-Oxidized
      Silicon Nanoparticles for Cellular Imaging Applications.
AB  - We have developed a versatile, one-step melt synthesis of water-soluble, highly
      emissive silicon nanoparticles using bi-functional, low-melting solids (such as
      glutaric acid) as reaction media. Characterization through transmission electron
      microscopy, selected area electron diffraction, X-ray photoelectron spectroscopy,
      and Raman spectroscopy shows that the one-step melt synthesis produces nanoscale
      Si cores surrounded by a silicon oxide shell. Analysis of the nanoparticle
      surface using FT-IR, zeta potential, and gel electrophoresis indicates that the
      bi-functional ligand used in the one-step synthesis is grafted onto the
      nanoparticle, which allows for tuning of the particle surface charge, solubility,
      and functionality. Photoluminescence spectra of the as-prepared glutaric acid
      synthesized silicon nanoparticles show an intense blue-green emission with a
      short (ns) lifetime suitable for biological imaging. These nanoparticles are
      found to be stable in biological media and have been used to examine cellular
      uptake and distribution in live N2a cells.

PMID- 23139439
TI  - Reliability of Children's Testimony in the Era of Developmental Reversals.
AB  - A hoary assumption of the law is that children are more prone to false-memory
      reports than adults, and hence, their testimony is less reliable than adults'.
      Since the 1980s, that assumption has been buttressed by numerous studies that
      detected declines in false memory between early childhood and young adulthood
      under controlled conditions. Fuzzy-trace theory predicted reversals of this
      standard developmental pattern in circumstances that are directly relevant to
      testimony because they involve using the gist of experience to remember events.
      That prediction has been investigated during the past decade, and a large number
      of experiments have been published in which false memories have indeed been found
      to increase between early childhood and young adulthood. Further, experimentation
      has tied age increases in false memory to improvements in children's memory for
      semantic gist. According to current scientific evidence, the principle that
      children's testimony is necessarily more infected with false memories than
      adults' and that, other things being equal, juries should regard adult's
      testimony as necessarily more faithful to actual events is untenable.

PMID- 23139441
TI  - Mechanical and In Vitro Biocompatibility of Brushite Cement Modified by
      Polyethylene Glycol.
AB  - Brushite (dicalcium phosphate dihydrate, DCPD) cement, owing to its high
      solubility in physiological condition and ability to guide new bone formation, is
      widely used to treat bone defects. In the present study, we have evaluated the
      effects of poly ethylene glycol (PEG) addition on the setting time, compressive
      strength and in vitro biocompatibility of brushite cement. The brushite cements
      were prepared by mixing beta-tricalcium phosphate [beta-TCP, Ca(3)(PO(4))(2)] and
      monocalcium phosphate monohydrate [MCPM, Ca(H(2)PO(4))(2). H(2)O]. PEG was
      introduced at 2.0 and 5.0 wt% with the liquid. Introduction of PEG resulted in
      marginal increase in both initial and final setting time; however, significantly
      affected the compressive strength. Effects of PEG incorporation on in vitro
      biocompatibility of brushite cements were studied by using human fetal osteoblast
      cells (hFOB) cells. Field emission scanning electron microscope (FESEM) images
      and immunohistochemical analysis indicated that pure and PEG incorporated
      brushite cement facilitates cell adhesion, proliferation and differentiation.
      Fewer cells expressed vinculin protein with increased PEG content in the cement.
      Cell proliferation was found to decrease with increased PEG concentration while
      the cell differentiation increased with PEG content. Our results provide a better
      understanding of in vitro biocompatibility of PEG added brushite cements that can
      be used to customize the cement compositions based on application need.

PMID- 23139442
TI  - Comparison of electrical conductivities of various brain phantom gels: Developing
      a 'Brain Gel Model'
AB  - The use of conducting gels to mimic brain and other tissues is of increasing
      interest in the development of new medical devices. Currently, there are few such
      models that can be utilized at physiologic temperatures. In this work, the
      conductivities of agar, agarose and gelatin gels were manipulated by varying NaCl
      concentration from 0-1 mg/ml. The AC conductivity was measured at room and
      physiological temperatures (37 degrees C) in the 100-500 Hz frequency range.
      Conductivity (sigma) was nearly independent of frequency but increased linearly
      with NaCl concentration and was higher at physiological temperatures in these
      gels. A formula for predicting conductivity as a function of NaCl concentration
      was derived for each gel type. The overall goal is to develop a 'brain gel
      model', for studying low frequency electrical properties of the brain and other
      tissues at physiological temperatures.

PMID- 23139443
TI  - Putting patients at the centre of eye care.

PMID- 23139444
TI  - Understanding what patients think about eye care - and our services.

PMID- 23139445
TI  - Improving our patients' experience: ideas for change.

PMID- 23139446
TI  - How to encourage patients to come for the eye services they need.

PMID- 23139447
TI  - Experiences in rural Kenya: Addressing lack of knowledge.

PMID- 23139449
TI  - Welcoming patients into our eye service.

PMID- 23139448
TI  - Experiences in a capital city: How we market our services.

PMID- 23139450
TI  - Improving patient flow through an eye clinic.

PMID- 23139451
TI  - Helping patients find their way to better diabetic retinopathy care.

PMID- 23139452
TI  - Community Eye Health Journal - promoting improvement in eye health for over 20
      years.

PMID- 23139453
TI  - Taping an eyelid closed.

PMID- 23139454
TI  - Checking and replacing fuses.

PMID- 23139455
TI  - Eliminating trichiasis: the next steps forward.

PMID- 23139456
TI  - Test your knowledge and understanding.

PMID- 23139457
TI  - An Investigation of Siloxane Cross-linked Hydroxyapatite-Gelatin/Copolymer
      Composites for Potential Orthopedic Applications().
AB  - Causes of bone deficiency are numerous, but biomimetic alloplastic grafts provide
      an alternative to repair tissue naturally. Previously, a hydroxyapatite-gelatin
      modified siloxane (HAp-Gemosil) composite was prepared by cross-linking (N, N'
      bis[(3-trimethoxysilyl)propyl]ethylene diamine (enTMOS) around the HAp-Gel
      nanocomposite particles, to mimic the natural composition and properties of bone.
      However, the tensile strength remained too low for many orthopedic applications.
      It was hypothesized that incorporating a polymer chain into the composite could
      help improve long range interaction. Furthermore, designing this polymer to
      interact with the enTMOS siloxane cross-linked matrix would provide improved
      adhesion between the polymer and the ceramic composite, and improve mechanical
      properties. To this end, copolymers of L-Lactide (LLA), and a novel alkyne
      derivatized trimethylene carbonate, propargyl carbonate (PC), were synthesized.
      Incorporation of PC during copolymerization affects properties of copolymers such
      as molecular weight, T(g), and % PC incorporation. More importantly, PC monomers
      bear a synthetic handle, allowing copolymers to undergo post-polymerization
      functionalization with graft monomers to specifically tailor the properties of
      the final composite. For our investigation, P(LLA-co-PC) copolymers were
      functionalized by an azido-silane (AS) via copper catalyzed azide-alkyne
      cycloaddition (CuAAC) through terminal alkyne on PC monomers. The new
      functionalized polymer, P(LLA-co-PC)(AS) was blended with HAp-Gemosil, with the
      azido-silane linking the copolymer to the silsesquioxane matrix within the final
      composite.These HAp-Gemosil/P(LLA-co-PC)(AS) composites were subjected to
      mechanical and biological testing, and the results were compared with those from
      the HAp-Gemosil composites. This study revealed that incorporating a cross
      linkable polymer served to increase the flexural strength of the composite by
      50%, while maintaining the biocompatibility of HAp-Gemosil ceramics.

PMID- 23139458
TI  - Mood Regulation in Real-Time: Age Differences in the Role of Looking.
AB  - Mechanisms have been proposed to underlie differences between younger and older
      adults in real-time mood regulation, but these mechanisms have not yet been shown
      to predict mood outcomes. One such mechanism is age-related positivity effects in
      attention and memory. In this paper, I take one form of this possible mechanism 
      positive looking patterns - and consider whether 1) older adults prefer positive
      looking, and 2) positive looking helps older adults regulate their mood in real
      time. Evidence is more consistent for the former than the latter. A similar
      exercise is needed for other possible forms (positive memory) and other possible
      mechanisms that may explain age differences in real-time mood regulation.

PMID- 23139459
TI  - Comparison of implant survival with implants placed in acceptable and compromised
      bone: a literature review.
AB  - BACKGROUND: Survival rates for conventional dental implant systems are relatively
      high in normal healthy bone. However, there are subgroups of patients that are at
      an increased risk of implant failure. In particular, patients with compromised
      quantity or quality of bone present a significant challenge to the dental
      implantologist. OBJECTIVE: To perform a review of the literature in an attempt to
      quantify the relative risk of implant failure in compromised bone compared to
      good or acceptable bone and to identify whether certain anatomical regions are at
      greater risk. SEARCH STRATEGY: We conducted a systematic electronic database
      search of Medline, Cinhahl and the Cochrane Library through March 2006
      identifying articles meeting the eligibility criteria. RESULTS: We calculated an
      increased risk of implant failure in compromised bone compared to healthy bone in
      both the maxilla and the mandible using conventional dental implant systems.
      Relative risks ranged from 2 to 12 with the highest risk of failure in the
      maxilla. Conventional systems are often used in combination or after bone
      augmentation procedures or more innovative methods for stimulating bone growth in
      patients with compromised bone. These approaches do have their limitations
      including high costs, the accumulation of the surgical risks, and delayed time to
      loading. DISCUSSION: Quantifying the risk of implant failure in patients with
      compromised bone should assist the implantologist in treatment decision making
      and patient counseling. Alternative methods for treating patients with
      compromised bone include zygomatic and lateral implants, neither of which
      typically require bone augmentation procedures. More studies are needed to
      evaluate their safety and efficacy.

PMID- 23139460
TI  - Three dimensional CT reconstruction: a comparison between 2D, 3D CT and original
      anatomical structures.
AB  - Conventional two dimensional computed tomography has provided significant
      advancement in clinical diagnosis with information on cross-sectional anatomy of
      various parts of the body. However, three dimensional representations are not
      directly available. This is now made possible by recent development of CAD
      software and CT equipments and technique such as multiplanar reformation capable
      of providing 3D reconstruction using 2D CT data. This article evaluates the
      accuracy of measurements and dimensions in 3D CT reconstruction.

PMID- 23139461
TI  - A comparative evaluation of rhytidectomy versus retromandibular approach for Open
      Reduction and Internal Fixation (ORIF) of mandibular condylar fractures.
AB  - OBJECTIVE: This clinical study was carried out on thirty patients who underwent
      open reduction and internal fixation for condylar fractures via
      rhytidectomy/retromandibular approach were evaluated. METHODS: Group I
      (rhytidectomy approach) were compared and evaluated clinically and radiologically
      with Group II (retromandibular approach) for the following parameters like
      surgical access, duration of surgery, anatomic reduction assessment with relevant
      radiographs, occlusal discrepancies, need for post operative IMF, facial nerve
      morbidity, other post operative complications and scarring. RESULTS: There was a
      statistically significant difference between the two groups in the duration of
      surgery which was found to be significantly lesser for group II than group I.
      Access was better in group I. Scar was well camouflaged in patients of Group I
      when compared to group II. CONCLUSION: The rhytidectomy (Face-lift) incision
      which we have used in our study has all the advantages of the retromandibular
      approach with an added advantage of a less conspicuous scar and a wider exposure
      of the fracture site. The only disadvantage is the added time required for the
      closure which is not a concern as the aesthetic outcome of this technique is
      superior to the other approaches.

PMID- 23139462
TI  - Fibula free flap splitting for mandible reconstruction: A technical note.
AB  - Conformation of the fibula flap to passively adapt to the remaining mandible may
      be indeed challenging. A review of the 'axial splitting' technique for fibula
      free flaps is presented with a novel method of osteosynthesis. Adequate
      mandibular angle shape is achieved by performing this type of osteotomy with a
      minimal use of titanium hardware for flap insetting.

PMID- 23139463
TI  - Removable Partial Prosthesis (RPP) with acrylic resin flange for the mandibular
      guidance therapy.
AB  - OBJECTIVES: Patients undergoing hemimandibulectomy suffer from mandibular
      deviation. The purpose of this article is to describe a new therapeutic
      possibility for the prosthetic management of these patients using only one device
      both for physiotherapy and eating. METHODS: A 56-year-old man's pre-existing
      mandibular removable partial prosthesis was modified to use as a partial
      prosthesis as a device to correct mandibular deviation. In fact, two precision
      attachments patrix were inserted into buccal surface of partial prosthesis base
      and corresponding matrix were inserted into a transparent acrylic resin guide
      flange. RESULTS: In this way the patient can use only one prosthesis both for
      physiotherapy and eating simply inserting and removing the guide flange. The
      transparent resin employ is important for the day by day use. CONCLUSION: This
      technique permits to use only one device both for mechanical correction of
      mandibular deviation and masticatory function while literature shows that two
      different devices are usually used in patients with mandibular deviation to
      satisfy both these functions.

PMID- 23139464
TI  - Alveolar bone grafts distal to the lower second molar.
AB  - INTRODUCTION: This paper presents case and technique reports on the use of Bio
      Oss(r) and Bio-Gide(r) implantable material for the establishment of a mineral
      and protein scaffold for reconstruction of the distal alveolus of the lower
      distal second molar (lower dM2). METHODS: Such 'alveolar bone grafts' were
      undertaken immediately following the removal of deep horizontal or mesio-angular
      impacted wisdom teeth, and which had the following associations. 1) Partial
      eruption of the third molar, 2) Preoperative radiographic (OPG) evidence of loss
      of bone height (>=3mm) below the distal Cemento-Enamel Junction (CEJ) of the
      lower dM2, and 3) Patient aged >=26 years of age. Following a presentation of
      radiographs (in three patients) taken preoperatively and postoperatively (at ~6
      months), a brief description of the technique is offered as well as a brief
      literature review on the subject. CONCLUSION: The author suggests that for older
      patients (>=26 years) were there is the presence of partially exposed deep mesio
      angular or horizontal impacted wisdom teeth, and which are associated with the
      radiographic appearance of bone loss to the distal surface of the lower second
      molar tooth, then alveolar bone grafting utilising Bio-Oss(r) and Bio-Gide(r) is
      an effective and stable treatment option to prevent development of periodontal
      pocketing in the area. The author advises for more guided and systematised study
      in this area.

PMID- 23139465
TI  - Mandibular cystic defect: A composite approach with rhBMP-2 and rib graft.
AB  - OBJECTIVE: To report treatment of severe mandibular defect caused by Aneurysmal
      Bone Cyst (ABC) in a 6-year-old child, with off-label use of Recombinant Bone
      Morphogenetic Protein-2 (rhBMP-2) STUDY DESIGN: Clinical Study. METHOD: After
      corrective segmental mandibulectomy, mandible was stabilized by precontoured
      titanium reconstruction plates spanning the entire defect. After confirming final
      diagnosis and a wait and watch approach, rhBMP-2 was inserted into mandibular
      defect along with conventional split rib graft. RESULT: New bone formation was
      identified at 3 months and was evident at radiographic examinations upto 5
      months. CONCLUSION: Reconstruction of a large mandibular defect was facilitated
      by use of an osteoinductive factor (rhBMP-2) as a graft additive. CLINICAL
      RELEVANCE: One-step salvage and reconstruction could be facilitated by use of an
      osteoinductive factor, as a graft additive, may be an alternative strategy for
      repair of large mandibular defects.

PMID- 23139466
TI  - Patient responses to vacuum formed splints compared to heat cured acrylic
      splints: pilot study.
AB  - OBJECTIVE: Vacuum formed and heat cured acrylic splints have been used in the
      diagnosis and treatment of temporomandibular disorders. The aim of this study was
      to evaluate patient's preference to either the vacuum formed or the heat cured
      acrylic splint. MATERIAL AND METHODS: Twenty patients planned to receive splints
      were chosen from the dental school. Both types of occlusal splints were
      fabricated for each of them. Each patient used the splints alternatively on a
      nightly basis for 3 weeks. After 3 weeks, each patient completed a questionnaire
      regarding the comfort, fit, retention, occlusal contact, taste, gingival and lip
      irritation, smoothness and smelling. Statistical analysis was conducted by the
      MacNemar's Chisquare test. RESULTS: There was no statistical difference in
      patient's responses to the different splint materials except for the comfort of
      wearing through the night. CONCLUSION: The vacuum formed and heat cured acrylic
      splint may be equally worn in patient preference for treatment of
      temporomandibular disorders.

PMID- 23139467
TI  - Oral injuries in children attending a hospital in Saudi Arabia.
AB  - AIMS: To determine the occurrence, causes, types and severity of oral trauma and
      the time elapsed until seeking dental care in children seen in a hospital in
      Jeddah, Saudi Arabia. MATERIALS AND METHODS: Data included all cases of oro
      facial trauma for children aged 17 years and younger who presented at the
      emergency and dental departments of the hospital during a 12-month period.
      RESULTS: A number of 112 patients with traumatic oral injuries visited the
      hospital during this period. 79 were males and 33 were females. The highest
      frequency of injury was seen in 9-11 year old children. The most common cause of
      trauma was due to falls (68%). Most of the dental injuries occurred in the street
      (57%). The most common types of injury were luxation injuries and complicated
      crown fractures. Maxillary teeth were more affected than mandibular teeth.
      Maxillary central incisors were found to be the most affected teeth. 51 patients
      had soft tissue injuries and 13 patients had facial bone fractures. The largest
      number of injuries presented on the same day for treatment (70%) or 1 day after
      (36%). CONCLUSION: From the data this study population showed trends and comman
      cases of paediatric traumatic oral injuries senn in a major hospital in saudi
      Arabia.The study helpred us in improving awarness regarding the oral injuries and
      importance of minimizing its complication through educational programs.

PMID- 23139468
TI  - Liquid nitrogen cryotherapy in the management of oral lesions: a retrospective
      clinical study.
AB  - BACKGROUND #ENTITYSTARTX00026; OBJECTIVES: The purpose of this study was to
      evaluate effectiveness and convenience of cryosurgical procedure, to assess the
      events during postoperative healing and to find out the incidence of recurrence
      MATERIALS AND METHODS: This study was conducted in the Department of Oral and
      Maxillofacial Surgery, KLESVK Institute of Dental Sciences, Belgaum. The 40
      patients selected for the study were divided into 2 groups of 20 patients each
      irrespective of age and sex. Group I 20 patients with Pre-Malignant Lesions Group
      II 20 patients with Oral Mucous Cyst RESULTS: It was observed that all the 20
      patients of mucocele were cured without any complication and recurrence, but in
      20 patients of leukoplakia 5 patients had recurrence which was directly
      attributed to their persisting habits. CONCLUSION: We state that this modality of
      treatment is promising with good results and has certain advantage over other
      modalities of treatment.

PMID- 23139469
TI  - Pulmonary function of adult Nigerians placed on intermaxillary fixation.
AB  - OBJECTIVE: The use of intermaxillary fixation to treat jaw fractures is a
      procedure still widely carried out in third world countries either because of the
      unavailability of miniplates to treat jaw fractures or due to their expensive
      nature. The purpose of this study was to determine the effects of intermaxillary
      fixation on ventilatory functions of adult Nigerians so as to establish baseline
      data for future comparisons in Africans. METHODS: One hundred and forty-eight
      subjects comprising 120 (81%) males and 28 (19%) females were studied. Their age
      ranged from 18 to 60 years with a mean age of 24 years. The patients' pulmonary
      function tests were done using a vitalograph spirometer to measure FEV(1) and FVC
      immediately postoperatively, 7 days postoperatively, immediately after removal of
      IMF, and on the 7th day of IMF removal. The mean values of the FEV(1) and FVC at
      7 days postoperatively were significantly higher than the values obtained
      immediate postoperatively (p<0.001). The FEV(1) and FVC values obtained immediate
      postoperatively and 7 days postoperatively were significantly lower than the
      values obtained immediately after removal of the wires (p<0.001). RESULTS: The
      results also show that there was a further increase of the mean values of FEV(1)
      and FVC on the 7th day of wires removal. CONCLUSION: It was observed that there
      was a reduction of pulmonary function values due to airway obstruction following
      IMF. The reduction was 5.7% to 8.9% in males, and 5.0% to 6.9% in females
      compared to the normal values established for adult Nigerians. In addition, the
      average of the mean FVC values immediately postoperatively and 7 days
      postoperatively were 87.9% and 90.9% for males and 91.7% to 93.6% for females
      respectively of their normal values obtained from the FVC values on the 7th day
      of wire removal.

PMID- 23139470
TI  - Decompression and cystectomy of the odontogenic keratocysts of the mandible: a
      clinical study.
AB  - OBJECTIVES: Owing to the aggressive nature of OKC's if one could stop or even
      reverse the growth of the cyst with a simple procedure like decompression,
      regardless of the histologic type, it would be an alternative to radical and
      disfiguring surgery. METHODS: Eight patients who were diagnosed with Odontogenic
      keratocyst of the mandible were chosen and the first stage of treatment being,
      insertion of the decompression stent into the most prominent or dependent part of
      the cystic cavity. Then based on assessment of regular second monthly OPG
      radiograph the second stage ie. Enucleation of the cyst and treatment of the
      cystic cavity with Carnoy's solution was carried out, when the size of the cystic
      cavity had decreased. RESULTS: The radiographs of all the patients were analyzed
      at a two month interval and compared with the pre operative radiograph. The
      percentage of change in radiodensity of the lesion ranged from 35.15% to 66.16%
      with a mean decrease of 53.85%. This also indicated that the quantum of bone
      regeneration which occurred simultaneously and as observed during the cystectomy
      procedure was commendable. CONCLUSION: Reduction of surgical morbidity while
      preserving anatomy and function, is the greatest advantage of decompression,
      however one should not forget the emphasis on the value of long term studies
      needed to be carried out with regular follow-up, to keep a check on those
      patients treated with decompression.

PMID- 23139471
TI  - Management of choanal atresia in cases of craniofacial malformation.
AB  - OBJECTIVE: To report the method and results of endonasal endoscopic approach in
      congenital choanal atresia in cases of craniofacial malformation. PATIENTS: The
      pathology of unilateral and bilateral choanal atresia and the treatment results
      in seven children treated between 1999 and 2006 are presented. 5 infants
      suffering from bilateral atresia also had severe malformations (Charge syndrome
      [2 patients], trisomy 18, microcephalus, central cranioschisis, cleft lip and
      anophthalmia 9). The surgical intervention was carried out immediately after
      birth. 2 patients with unilateral atresia were treated in their second and sixth
      year of life respectively. CT scan was the diagnostic procedure of choice.
      Intraoperative endoscopy showed both membraneous and osseous atresia. SURGICAL
      PROCEDURE: Trocars of different sizes were used to open the atresia plate, while
      the osseous parts were removed with diamond drills. Silicone tubes were inserted
      transnasally and remained in place for several months to improve the
      infants'ability to breath and drink. RESULTS: In all cases of bilateral atresia
      the tubes either had to be changed repeatedly or replaced with larger tubes due
      to dislocation and head growth. The septum was perforated in one case. No further
      stenoses were detected following the removal of the tubes (after 3-6 months).
      CONCLUSION: The transnasal access is particularly suited to newborns and infants
      because it induces a minor surgical trauma and carries a low risk of bleeding if
      endoscopes are used. The results show that the risk of restenoses can be
      minimised with sufficient fixating and in-patient care.

PMID- 23139472
TI  - The combined analgesic effect of gabapentin and transdermal fentanyl patch on
      acute and chronic pain after maxillary cancer surgeries.
AB  - Purpose of this study was to evaluate the combined analgesic effect of gabapentin
      and transdermal fentanyl patch, on acute and chronic pain after surgery for
      maxillary cancer. STUDY DESIGN: The Study was double blind and prospective. 100
      subjects belonging to ASA grade I and II, 30-50 years age group, scheduled for
      maxillary cancer surgery were randomized into two groups; treatment group (GT):
      to receive gabapentin, transdermal fentanyl patch or control group (c): two
      placebos. For acute postoperative pain (Visual Analogue Score) and analgesic
      requirements were assessed 2, 4, 8 hours and 7 days after surgery. Subjects were
      also assessed for chronic pain 2, 4, 6 months later. RESULTS: Subjects in
      treatment group required lesser dose of analgesic, as compared to control group,
      in the post operative period. Visual Analogue Scores were also significantly
      lower in the treatment group throughout the post operative period. Occurrence of
      side effects was non significant between both groups. 2, 4 and 6 months after
      surgery, 40, 35 and 28 subjects respectively, out of total 45 subjects of the
      control group, reported chronic pain. In comparison, 25, 10 and 4 subjects out of
      42 subjects in the treatment group reported chronic pain 2, 4, 6 months
      respectively after surgery. 15, 10 and 6 out of 45 of the control group required
      analgesics, whereas 2, 0 and 0 out of 42 in the treatment group, required
      analgesics respectively 2, 4 and 6 months after surgery CONCLUSION: Acute and
      chronic pain after maxillary cancer surgery is significantly reduced by
      multimodal analgesia.

PMID- 23139473
TI  - Head and neck teratomas.
AB  - Teratomas are complex lesions composed of diverse tissues from all 3 germinal
      cell layers and may exhibit variable levels of maturity. Head and neck teratomas
      are most commonly cervical with the oropharynx (epignathus) being the second
      commonest location. In this article, clinical presentation, behaviour and
      associated significance of head and neck teratomas have been highlightened.
      Because of their obscure origin, bizarre microscopic appearance, unpredictable
      behaviour and often dramatic clinical presentation, a dental surgeon or a dental
      specialist should be aware of their clinical presentation and pathology.

PMID- 23139474
TI  - Use of hypertonic saline in the management of parotid fistulae and sialocele: a
      report of 2 cases.
AB  - Parotid fistula is a well known complication of parotidectomy or penetrating
      injury of the parotid gland. Fistulae may be internal or external, but simple
      internal fistulae are of no surgical interest. In cases of external fistulae, the
      principles of management aim at the return of normal parotid function in both
      acute and chronic parotid injury, but sometimes the alternative is to depress
      parotid secretions to allow natural healing process to seal the injury.The paper
      highlights the indications, techniques, advantages and disadvantages of using
      osmotic sclerosant for the management of parotid fistulae. We used warm
      hypertonic saline injections within the glandular substance to cause rapid
      fibrosis of the gland in 2 patients of chronic parotid fistulae.This technique is
      a simple and effective method of dealing with salivary leak. Its ease of
      performance, effectiveness; minimal surgical risk and minor cost are the
      advantages over other available options.

PMID- 23139475
TI  - The repositioning Nance appliance: a fixed functional appliance and case report.
AB  - Functional appliances are primarily orthopaedic tools used to influence the
      facial skeleton in a growing child. These appliances may be fixed or removable. A
      fixed functional appliance referred to as the Repositioning Nance Appliance (RNA)
      was developed and a case report is presented. The RNA is a fixed functional
      appliance consisting of bands on the upper first molars joined together with a
      0.036-inch stainless steel wire that is bent around the anterior contour of the
      palate. Just lingual to the upper incisors the wire is complemented with an
      acrylic Nance button, which is modified with a downward and backward incline
      projection. The labial aspect of this projection is smooth and when the lower
      incisors come into contact with it, they are directed into an edge-to-edge
      relation with the upper incisors, brought about by forward positioning of the
      mandible. This has the net effect of relocating the mandible into a Class I
      relation. A 14-year-old boy in his late mixed dentition stage of dental
      development presented with mild crowding, a horizontal growth pattern and a
      skeletal Class II jaw relation caused by an underdevelopment of the mandible.
      Treatment was initiated using the RNA and continued for a period of 18 months.
      This was followed by full fixed appliances for another 12 months and resulted in
      Class I skeletal and dental relations, a reduced overjet and an improved facial
      profile. The RNA, if applied correctly is a simple fixed functional appliance
      that can be used with confidence, comfort and economy to both the patient and
      orthodontic practitioner.

PMID- 23139476
TI  - Early orthodontic management of Crouzon Syndrome: a case report.
AB  - Crouzon Syndrome is an autosomal dominant disorder with complete penetrance and
      variable expressivity. Described by a French neurosurgeon in 1912, it is a rare
      genetic disorder. Crouzon syndrome is caused by mutation in the fibroblast growth
      factor receptor 2 (FGFR2) gene. The disease is characterized by premature
      synostosis of coronal and sagittal sutures which begins in the first year of
      life. Once the sutures become closed, growth potential to those sutures is
      restricted. However, multiple sutural synostoses frequently extend to premature
      fusion of skull base causing midfacial hypoplasia, shallow orbit, maxillary
      hypoplasia and occasional upper airway obstruction.The case of a 7-year-old South
      African black boy with Crouzon Syndrome is presented. He presented with
      characteristic triad of cranial deformity, maxillary hypoplasia and exophthalmos.
      The clinical, cephalometric features and initial orthodontic management of this
      patient are discussed as part of multidisciplinary management.

PMID- 23139477
TI  - Prosthetic rehabilitation of necrotic maxilla sequelae of faulty denture: report
      of a rare case.
AB  - Faulty complete denture can lead to deleterious effects on residual ridges. These
      deleterious effects are further severed if patient is systematically compromised
      as in Diabetes mellitus. Decreased resistance to infection, vascular changes, and
      altered tissue response seen in uncontrolled Diabetes when coupled with faulty
      denture prosthesis can even lead to gangrenous necrosis.Prosthodontic management
      of edentulous patient with maxillary defect is a challenging task because there
      is reduced denture bearing surface compromising adhesion, cohesion and peripheral
      seal thus affecting retention adversely; reduced support area for denture; air
      leakage due to poor stability; retentive deficiencies and movement of prosthesis
      during function. Prosthetic rehabilitation for these patients can be accomplished
      with minor modifications in procedures like incremental shaping technique for
      taking impression, modifications in jaw relation, tooth arrangement, and
      fabrication of hollow bulb obturator along with atraumatic and meticulous care
      during all the procedures.This clinical report describes a case of gangrenous
      necrosis of premaxilla caused due to a faulty previous prosthesis; and its
      prosthodontic management.

PMID- 23139478
TI  - Branchial cleft cyst versus dermoid cyst of digastric triangle: report of two
      cases.
AB  - Lateral neck soft tissue masses manifests with variable etiologies, clinical
      signs and symptoms. Although these lesions are congenital in nature,
      manifestations of these may not occur until adulthood. Also some of these lesions
      may undergo malignant transformations.We present two cases with lateral neck
      swellings which were excised successfully under general anaesthesia and later
      confirmed histopathologically as dermoid and branchial cleft cysts.Formulation of
      an appropriate diagnosis is necessary and requires a clinician to bear a host of
      skills to systematically arrive at a correct treatment plan. Use of advanced
      imaging techniques such as ultrasonography and magnetic resonance imaging along
      with proper knowledge of anatomy, pathology and application of basic surgical
      principles goes a long way in successful and uneventful management of such
      lesions, as these may overlap many important neurovascular structures or may in
      turn be wrapped by them.

PMID- 23139479
TI  - Oral cysticercosis: a case report.
AB  - Cysticercosis is a common disease in developing countries. Oral lesions produced
      by this parasitic infestation are rare [1-7]. Diagnosis is usually made on
      microscopic examination. Following is a case report of a 19-year-old female
      patient from central India who reported to our centre with a swelling in the left
      cheek, which was diagnosed as cysticercosis on Fine Needle Aspiration Cytology
      (FNAC).

PMID- 23139480
TI  - Two atypical case reports of foreign bodies in the maxillary sinus and nasal
      septum.
AB  - We present cases with foreign bodies in maxillary sinus and nasal septum which
      was due to peculiar habit of the patient of inserting sticks in between teeth.
      There was oroantrualfistula and nasal abcess observed. The ectopic foreign bodies
      were removed surgically.

PMID- 23139481
TI  - Acute airway distress secondary to iatrogenic injury during Tracheostomy.
AB  - Laceration and perforation of the membranous trachea are uncommon. We present a
      case of bilateral Pneumothorax, which developed subsequent to iatrogenic injury
      during tracheostomy.

PMID- 23139482
TI  - A rare case of simultaneous surgery of an odontogenic space infection and
      delivery by caesarean section in a pregnant patient.

PMID- 23139483
TI  - Fiberoptic assessment of laryngeal mask airway placement: a comparison of blind
      insertion and insertion with the use of a laryngoscope.
AB  - BACKGROUND AND OBJECTIVES: This study aims to compare the frequency of ideal
      anatomic placement of the Laryngeal Mask Airway (LMA) using the traditional blind
      insertion approach with one where placement was facilitated by the use of a
      laryngoscope. Laryngeal Mask Airway is a supraglottic device in providing general
      anaesthesia. METHODS: A prospective comparison of 60 patients divided into 2
      groups (30 with the blind technique and 30 with the direct technique) were
      evaluated with 2 airway assessment methods, Wilson and Mallampati. We also
      considered whether there was a relationship between these criteria and the
      successful placement into an ideal position. Other variables were considered,
      including hemodynamics. Five placement visual ordinals were used to grade the LMA
      position. RESULTS: There was no statistically significant difference between
      group 1 and group 2 (P=0.279) in terms of Campbell category. There was no
      statistically significant relation between Wilson airway score or Mallampati
      class and Campbell category (p=0.633 and 0.239 respectively). There was no
      statistically significant difference in systolic and diastolic BP at 1, 2 and 5
      min post insertion between the two groups, but there was a statistically
      significant difference in 1 and 2 minute post insertion pulse rate (P=0.004).
      CONCLUSION: Blind insertion technique is easier and simpler method for insertion
      of LMA and has a reasonable success during insertion, so it is recommended to be
      used.

PMID- 23139484
TI  - Comparison of various approaches for exposure of infraorbital rim fractures of
      zygoma.
AB  - OBJECTIVE: The aim of this study was to randomly compare four
      incisionssubciliary, subtarsal, infraorbital and transconjunctival with lateral
      canthotomy for treatment of orbital rim or floor fractures. METHODS: 40 patients
      with zygomatic complex fractures either isolated or in association with pan
      facial fractures, were selected for the study. They were divided into four groups
      of 10 patients each, Group I-Transconjunctival with lateral canthotomy, Group II
      Subciliary [single eyelid incision], Group III-Subtarsal incision, and Group IV
      Infraorbital incision. The following parameters were compared a) The average time
      from incision to fracture exposure b) The amount of exposure of the site provided
      c) The aesthetic appearance of the 'scar' d) Complications e) Factor of 'time' -
      its effect on scar and complications. RESULTS: The study revealed that all four
      incisions provided adequate exposure of fracture site and transconjunctival (22
      minutes) required the maximum time for exposure. The complications included
      ectropion in group I and prolonged edema in group IV. Group II and III patients
      had relatively lesser number of complications. Group IV patients had visible scar
      as compared to no scar in group I patients. CONCLUSION: We conclude by saying
      that transconjunctival approach provides an excellent aesthetic result when done
      meticulously. However the subciliary and the subtarsal incisions provide a more
      rapid, direct approach to the orbital floor and infraorbital rim with minimal
      morbidity and an aesthetically acceptable scar. The infraorbital incision is the
      least acceptable aesthetically.

PMID- 23139485
TI  - Classification of the maxillary sinus according to area of the medial antral
      wall: a comparison of two ethnic groups.
AB  - OBJECTIVES: This study is an anatomical study designed to benefit surgeons
      working in the region of the maxillary sinus. This paper investigates ethnic and
      gender variations in the shape of the maxillary sinus in dried crania from the
      Raymond Dart collection of human skeletons. The paper claims that an estimate of
      the area of the medial antral wall of the maxillary sinus is one of the best
      ethnic/gender group predictors. METHODOLOGY: Helical, multislice computed
      tomography was performed using 1mm coronal slices length, depth, width and volume
      measurements for each sinus were taken. Classification by shape and estimated
      area of medial wall was attempted. RESULTS: Shape classification was found to be
      unsuccessful whilst medial wall classification into ethnic/gender groupings gave
      encouraging results. CONCLUSION: The area of the medial wall is related to
      ethnic/gender groups.

PMID- 23139486
TI  - Prevalence of periodontal pathogens in coronary atherosclerotic plaque of
      patients undergoing coronary artery bypass graft surgery.
AB  - BACKGROUND: Chronic bacterial infections have been associated with an increased
      risk for atherosclerosis and coronary artery disease. The ability of oral
      pathogens to colonize in coronary atheromatous plaque is well known. The aim of
      our study was to detect the presence of four common periodontal pathogens in
      coronary plaques. We detected the presence of 16S rRNA of Treponema denticola,
      Eikenella Corrodens, Porphyromonas gingivalis and Campylobacter rectus in
      subgingival and atherosclerotic plaques of CABG surgery by using Polymerase Chain
      Reaction. METHODS: 51 patients in the age group of 40 to 80 years with chronic
      periodontitis were recruited for the study. These patients were suffering from
      Coronary Artery Disease (CAD) and underwent Coronary Artery Bypass Grafting
      (CABG). DNA was extracted from the subgingival plaque and coronary atheromatous
      plaque samples. Universal Primer for the general detection of bacterial DNA and
      the primers for T.denticola, E. Corrodens, C.rectus and P.gingivalis were used to
      amplify part of 16SrRNA gene by Polymerase Chain Reaction. RESULTS: T.denticola,
      E.corrodens, C.rectus and P.gingivalis were detected in 49.01 %, 27.45 %, 21.51%
      and 45.10% of atherosclerotic plaque samples. In both subgingival and coronary
      plaque samples, T. denticola was detected in 39.21% of the cases, E.corrodens in
      19.60%, C.rectus in 11.76% and P.gingivalis in 39.22% of the cases respectively.
      CONCLUSION: Our study revealed the presence of significant bacterial DNA of oral
      pathogens in coronary plaques. This suggests possible relationship between
      periodontal infection and atherosclerosis and can help devise preventive
      treatment strategies.

PMID- 23139487
TI  - Morphological cell typing of osteoid clones derived from human bone marrow.
AB  - OBJECTIVE: Bone Marrow Stem Cells (BMSC) are a 'reservoir' for bone regeneration.
      BMSC can be studied in vitro by cloning cells which are improperly named
      colonyforming units of fibroblasts (CFU-f). Thus we decided to study CFU-f
      organization and morphology to have (A) a parameter by which to compare normal
      and pathologic conditions and (B) to potentially select the most osteogenic
      clones. METHODS: Two hundred and forty bone samples were collected from 109
      patients and primary cultures performed. RESULTS: After two weeks 9 cell types
      and 6 well organized types of colonies were detectable. Some have alkaline
      phosphatase (AP) activity. CONCLUSION: These data could be relevant to estimate
      the potential regeneration of bone.

PMID- 23139488
TI  - Osteoporosis and oral bone resorption: a review.
AB  - This paper is a summary of the published studies on the possible association
      between osteoporosis and alveolar bone loss. Osteoporosis and low bone mass are
      considered as a major public health problem. The mandible like other bones of the
      body has a series of anatomical landmarks that can serve as radiographic
      indicators. Using these indicators it is possible to evaluate changes in bone
      with respect to its quantity or quality by different methods of taking images.
      Higher bone resorption was detected in women with a higher number of pregnancies.
      Also, the higher educated the patient, the less bone resorption. Women with a
      background of backaches had more bone resorption to those who did not have this
      backache background. Finally, it was recognized that it would be possible to
      clear the quality dimension of the process of mandibular bone resorption. If we
      can identify the osteoporotic process using a basic panoramic radiography
      measurement technique, then it is possible to intercept the progress of the
      disease through early warning and treatment. From the results of this study, it
      can be concluded the thickness of the mandibular angular cortex can be used as an
      index for bone resorption. A healthy lifestyle has multiple benefits for the
      mouth and throughout the body. Dental professionals can play a role in preventing
      osteoporosis by reinforcing this message.

PMID- 23139490
TI  - Interposition of lateral pterygoid in temporomandibular joint ankylosis.
AB  - Conventionally temporalis myofascial flap is popular for interposition in TMJ
      ankylosis. Medial pterygoid and masseter also has been used in the past for
      interposition. We introduce here lateral pterygoid for interposition in cases of
      mild ankylosis where condylar bony architecture is not distorted.

PMID- 23139489
TI  - Keratocystic odontogenic tumor: a review.
AB  - The odontogenic keratocyst is a very well known odontogenic cyst. There are many
      types of cysts of the jaws, but what makes the odontogenic keratocyst unusual are
      its characteristic histopathological and clinical features, including potentially
      aggressive behaviour, high recurrence rate, and an association with the nevoid
      basal cell carcinoma syndrome. The characteristic histologic feature i.e. the
      presence of parakeratin, is unique amongst all the different inflammatory and
      developmental cysts that occur in the jaws. Many treatment modalities have been
      advocated for its treatment, but none in particular has been regarded as the best
      treatment option. The 2005 WHO classification now uses the term 'keratocystic
      odontogenic tumor'. We present a review of treatment modalities of the KCOT.

PMID- 23139491
TI  - Pedicled BFP for closure of oro-antral fistula revisited.
AB  - The Buccal Fat Pad (BFP) has been increasingly employed in the reconstruction of
      intra-oral defects since the procedure was first described by Egyedi. Although
      the use of BFP for closure of oro-antral communications has been reported in
      literature, it is either not a common practice or is under reported in India.
      This article describes predictive results with 2 cases of chronic oro-antral
      fistula using pedicled BFP.

PMID- 23139492
TI  - Options in orbital floor reconstruction in blowout fractures: a review of ten
      cases.
AB  - OBJECTIVE: The purpose of this case series was to assess the aesthetic and
      functional outcome of orbital floor reconstruction performed with calvarial bone
      graft, titanium mesh or prolene mesh. METHODS: Ten cases of orbital blowout
      fractures treated at our centre from October 2006 to July 2008 were considered
      for this study. Clinical examination, patient satisfaction and radiographic
      investigations were used to assess repaired fractures. RESULTS: Prolene mesh was
      used in four cases, titanium mesh was used in four cases and calvarial graft used
      in two cases. Nine patients had significant improvement in their esthetic
      appearance. Symmetry was restored in all cases. All ten cases had a noticeable
      improvement in the function. Of total ten cases six had diplopia, three recovered
      completely during the six months after the surgery. Three cases showed
      improvement later. All ten cases with enopthalmos recovered completely. Of the
      nine patients with infraorbital numbness, all recovered completely during the six
      months following surgery. One patient where the reconstruction was done with
      calvarial bone graft showed mild discrepancy in the ocular level. CONCLUSION: For
      small, linear defects measuring less than 2cm with enopthalmos and restricted
      ocular movements, prolene mesh (four cases) was used. For larger defects and
      impure blowout fractures involving the infraorbital rim, calvarial graft (two
      cases) or titanium mesh (four cases) was used. The outcome of surgery with all
      three materials was satisfactory. No postoperative complications were seen except
      for mild hypoglobus in a case reconstructed with calvarial graft. All three
      materials, calvarial graft, titanium mesh, prolene mesh, have the potential to be
      useful reconstructive materials in orbital floor blowout fractures.

PMID- 23139493
TI  - Autogenous mandibular symphysis graft for orbital floor reconstruction: a
      preliminary study.
AB  - OBJECTIVE: The present study aimed to evaluate and analyze postoperative results
      of Autogenous Mandibular Symphysis graft material for orbital floor
      reconstruction. MATERIAL AND METHODS: A retrospective study was conducted on 11
      patients, having an isolated blow out fracture (n=4) or orbital floor defects
      associated with other fractures (n=7). These fractures were reconstructed with
      Mandibular symphysis bone grafts. The Grafts were used where the defects were
      more than 1.5 centimeter [1]in diameter. Follow up as long as 1.5 year was kept.
      Patients were evaluated at recall visits by checking various extraoccular
      movements. Evidence of any complications like diplopia or enopthalmos, or
      rejection of graft or any symptoms of infection, or of paresthesia was recorded.
      RESULTS: During a 1.5 year period of follow up, most of the patients had no
      postoperative complaints. There was good restoration of the orbital floor, with
      no clinical evidence of enopthalmos or diplopia. Extraoccular movements were
      intact in all patients. Only one patient presented with the symptoms of infection
      at a follow up period of 9 months. The infection subsided after removal of
      titanium plates, used for the stabilization of graft. CONCLUSION: Autogenous
      Mandibular Symphysis graft is a good alternative with minimal morbidity for
      orbital floor reconstruction. The contour as well as the size of the graft
      available from symphysis region best suits for orbital floor reconstruction.

PMID- 23139494
TI  - A comparison between 2.0-mm standard and 2.0-mm locking miniplates in the
      management of mandibular fractures.
AB  - PURPOSE: The purpose of this clinical study was to compare effectiveness of 2.0
      mm locking miniplates and screws with 2.0-mm standard miniplates and screws in
      treating mandible fractures. PATIENTS AND METHODS: A randomized prospective study
      comprising of 40 samples, where 20 patients (group 1) were treated with locking
      plates and 20 patients (group 2) were treated with standard miniplates. All the
      cases were evaluated for the type of fracture, need for the Intermaxillary
      Fixation (IMF) and its duration, duration of surgery, anatomic reduction,
      paresthesia / neurosensory changes, occlusal discrepancies, infection at the
      fracture site and any need for the removal of the plates and screws. RESULTS: In
      our study Road Traffic Accidents (RTA) accounted for the majority of patients 30
      (70%). RTA was more prevalent (52.5%) in 21-30 age group, with assault being more
      common (67%) in 25-35 years. There was a significant difference between group 1
      and 2 in postoperative occlusal discrepancy and need for IMF (p=0.008). There was
      no significant difference in complication rates between group 1 and group 2
      patients. CONCLUSION: Locking plate/screw system proved to be more rigid than
      conventional plate/ screw system, thereby reducing the need and duration of IMF.
      However there was no significant difference in complication rates.

PMID- 23139495
TI  - Pediatric injuries in maxillofacial trauma: a 5 year study.
AB  - Fractures of the facial skeleton in children are less frequent. This clinical
      retrospective study of 5 year was conducted on 95 patients aged less than 16
      years who sustained maxillofacial injuries during the period 2003 to 2008. Age,
      sex, etiology incidence and type of fracture were studied. The ratio of boys to
      girls was 1.9:1. The 7-12 year age group was commonly involved and the highest
      incidence was at age of ten years. Falls were the most common cause of injury
      accounting for 41%, followed by road traffic accidents (30%). Sports related
      injuries, assault and child abuse were also the causes of injury in children.
      Dentoalveolar injuries were found to be highest incidence with 42.1% followed by
      mandibular fractures. The soft tissue injuries were associated the pediatric
      maxillofacial trauma were found to be 34.7% of all cases.

PMID- 23139496
TI  - Predictive variables for difficult intubations in oral and maxillofacial surgery.
AB  - SUMMARY: Many factors affect the difficulty of endotracheal intubation some of
      which are related to the condition of the patients. A few assessment tools have
      been developed to predict intubation difficulty but none is all inclusive thereby
      being inadequate for comprehensive and accurate evaluation. We assessed the
      usefulness of four categories of predictive variables namely; the LEMON score,
      Demographic indices, Tumour site and Intraoral Position of tumour (IOP), in
      predicting intubation difficulty among a group of patients with orofacial
      tumours. By statistical analysis, a significant correlation between predictions
      by LEMON score and actual intubation difficulty was observed while neck mobility
      (P=0.28) and Mallampati scores (P=0.49) were the most important criteria in the
      scoring system. Significant association was also observed with demographic
      indices and difficulty whereby the Optimal Interincisal Distance (OID) had the
      greatest impact (P=0.048). There was no difference in the difficulty posed by the
      different sites and intraoral positions of tumours in this study. We therefore
      suggest the adoption of the LEMON score and consideration of the demographic
      indices when assessing patients with orofacial tumours for intubation difficulty.
      Three important variables should be given greater value, these are, neck
      mobility, Mallampatti score and optimal interincisal distance.

PMID- 23139497
TI  - A study on coronal incision for treating zygomatic complex fractures.
AB  - OBJECTIVE: To study the value of coronal incisions for treating zygomatic complex
      fractures and evaluate the advantages, indications and complications associated
      with it. METHOD: In this prospective study, 12 patients were randomly selected
      regardless of age, sex requiring open reduction and internal fixation of
      communited zygomatic complex fractures with or without other associated fractures
      of the midface. Patients were all treated by coronal approach for open reduction
      and internal fixation of fracture of the zygomatic complex. Other local incisions
      were used if required. RESULTS: In all cases postoperative complications were
      relatively minor except in one case were the temporal branch of facial nerve
      weakness persisted at 3 months. Whereas 5 cases reported with slight weakness of
      the temporal branch of the facial nerve which resolved at the end of 3 months.
      The time taken for exposure of the fracture site via the coronal incision had a
      mean of 28.7 minutes. There were no cases of flap infection and just 1 case of
      stitch abscess reported. The same case later reported with a hypertrophic scar
      formation of greater than 0.5cm at 3months. In all other cases scar formation was
      negligible and well hidden within the hairline. There were no reported cases of
      paraesthesia at the operated site or hollowing of the temporal fossa. CONCLUSION:
      The coronal incision provides excellent access to the zygomatic arch and
      zygomatic complex, aiding in good anatomical reduction and also has the added
      advantage of the scar hidden in the hairline. It also has disadvantages like long
      operating time, risk of facial nerve injury, scarring in patients with male
      pattern baldness, paraesthesia of operated site etc. Therefore the incision
      should be judiciously used and not overused and indications strictly applied.

PMID- 23139498
TI  - Salivary gland neoplasms: an analysis of 74 cases.
AB  - Between 2006 and 2009, 74 cases of salivary gland neoplasms were analyzed
      retrospectively, of which 44 (60%) were benign and 30 (40%) malignant. 61 %
      percent of neoplasms were in the parotid gland, 22% in the minor salivary glands
      including sublingual salivary glands, and 17% in the submandibular glands. The
      most common benign neoplasm was pleomorphic adenoma (64%), and the most common
      malignant neoplasm were adenoid cystic carcinoma (17%) and mucoepidermoid
      carcinoma (23%). We analyze the incidence and distribution of all types of
      salivary gland neoplasms in our series, and provide data for comparison with
      other epidemiological studies from different geographical sites and races.
      Demographic data from these studies help us to a better understanding of the
      biological and clinical characteristics of the disease. Further epidemiological
      surveys should be encouraged for better understanding of the disease and to
      provide early and better treatment of salivary gland neoplasms.

PMID- 23139499
TI  - A comparitive study of diclofenac transdermal patch against oral diclofenac for
      pain control following removal of mandibular impacted third molars.
AB  - OBJECTIVE: The objectives of this study was to evaluate subjectively the
      analgesic efficacy of Oral Diclofenac Sodium against Diclofenac Sodium
      Transdermal patch in the management of postoperative pain following surgical
      removal of impacted mandibular third molars. MATERIALS AND METHODS: Twenty
      healthy subjects belonging to both the sexes in the age group of 18-40 years with
      bilateral mesioangular impactions of mandibular third molar teeth underwent
      surgical removal under local anaesthesia by administering an inferior alveolar
      nerve block on two different occasions with a minimum interval of 1 week in
      between the procedures. The postoperative pain was recorded on visual analog
      scale, a verbal rating scale, a pain relief scale and a pain intensity scale.
      Readings were taken at 2 hours, 4 hours, 8 hours, 12 hours and 24 hours
      postoperatively, taking the time at which the surgery was completed as a
      reference. On the second and third days, the repeat medication was administered
      at that reference time and recordings taken at the same intervals for a total of
      3 days. Patients received the study medication i.e. Diclofenac Sodium 100mg once
      a day for 3 days after performing surgery on one side and the same patients were
      given Diclofenac Sodium Transdermal Patch 100mg once a day for 3 days after
      performing surgery on the contralateral side. RESULTS AND OBSERVATIONS: Both the
      statistical analysis and clinical observation showed that on the first
      postoperative day diclofenac sodium administered orally has slightly more
      significant efficacy when compared to the drug administered transdermally.
      However, on the second and third postoperative days there was no statistical or
      clinical difference in the pain control by either route of administration.
      CONCLUSIONS: The study concludes that transdermal diclofenac sodium can be used
      as an alternative form of pain control following removal of impacted mandibular
      third molars, however considering that the analgesic potency might be lesser in
      the immediate postoperative period, it might be prudent to use oral diclofenac
      sodium for immediate postoperative pain relief, following which transdermal route
      can be used for pain control.

PMID- 23139500
TI  - Complex facial trauma with combined surgical and orthodontic rehabilitation.
AB  - Severe panfacial trauma require broad reconstructive procedures. As in the case
      presented, a primary reconstruction with ideal aesthetic outcome cannot be
      reached in every case. If not, these cases often require further reconstructive
      procedures. What this can be and how long this could take, this article intends
      to show. This case report presents the history of a today 30 year old male
      patient with a severe central midfacial comminuted fracture with preexisting
      Angle class II and comprehensive reconstruction.

PMID- 23139501
TI  - A chronicle of Tessier no. 0 and 1 facial cleft and its surgical management.
AB  - Description and successful management of a patient with Tessier no. 0 and 1
      facial cleft is being presented. This bizarre coexistence of two of the rare
      facial clefts in a single patient deserves a place in the cleft database.
      Appropriate evaluation was done to rule out the presence of median cleft face
      syndrome. Lip cleft was repaired by straight line technique with staggering at
      the vermilion border. Nasal cleft was reconstructed by replacing the missing
      lower lateral cartilage with conchal cartilage via endonasal approach.
      Satisfactory outcome was achieved for this singular deformity by conforming to
      the basic tenets of plastic surgery.

PMID- 23139502
TI  - Temporary pupillary dilatation and ptosis: complications of PSA nerve block: a
      case report and review of literature.
AB  - Lidocaine, an amide local anesthetic is administered regularly for the minor oral
      and dental surgical procedures. In this article, ophthalmic complications arising
      from Posterior superior nerve block are discussed and a case report which had
      dilatation of pupil and ptosis of eye lids is presented. A review of literature
      is done regarding the ophthalmic complications. The precautions one needs to take
      during the administration of Local Anesthesia (LA) especially Posterior Superior
      Alveolar nerve block and management guidelines are highlighted.

PMID- 23139503
TI  - Gorlin's syndrome - Report of a case and management of cystic lesions.
AB  - Gorlin's syndrome associated with multiple cystic lesions is a rare and uncommon
      condition. It is characterized by cutaneous basal cell carcinomas, multiple
      keratocysts in the jaw bones and skeletal anomalies. A case is presented with
      multiple odontogenic keratocyst and dentigerous cysts occurring in all quadrants
      of oral cavity with features suggestive of Gorlin's Syndrome. The clinical
      presentation and the management of these multiple cystic lesions and a two year
      follow up study is presented.

PMID- 23139504
TI  - Ramsay-Hunt syndrome complicating osteonecrosis of edentulous maxilla and
      mandible: report of a rare case.
AB  - Review of literature revealed atleast 30 cases of post herpes zoster
      osteonecrosis of maxilla or mandible. To our knowledge this is a first reported
      case of Ramsay-Hunt syndrome with post herpetic neuralgia and post herpes zoster
      osteonecrosis of edentulous maxilla and mandible. We have briefly reviewed the
      pathophysiology and management of post herpes zoster osteonecrosis and post
      herpetic neuralgia.

PMID- 23139505
TI  - Medpor in maxillofacial deformities: report of three cases.
AB  - OBJECTIVE: This paper deals with the usefulness and versatility of the porous
      high-density polyethylene implants for correction of various facial deformities
      as an augmentation and an onlay graft material with its advantages. MATERIALS AND
      METHODS: Prefabricated porous high-density polyethylene implants were used in
      three patients (post-trauma facial deformity, Goldenhar syndrome, nasal deformity
      in cleft patient) for secondary reconstruction of orbital floor, depressed nose
      and supra-orbital ridge, augmentation of hypoplastic mandible and depressed nasal
      dorsum under general anaesthesia. RESULTS: Good esthetic results were achieved in
      all the three patients treated with porous high-density polyethylene implants
      with no complications. CONCLUSION: Porous high-density polyethylene alloplastic
      implant is an excellent biomaterial for reconstruction of various facial
      deformities with many advantages over autogenous and other alloplastic materials.

PMID- 23139506
TI  - Malignant fibrous histiocytoma: a case report.
AB  - Malignant Fibrous Histiocytoma (MFH) is a controversial soft tissue malignancy
      whose pathogenesis continues to be redefined. It remains the most often used term
      for soft tissue sarcomas of late adult life. It has also been described to
      originate from the bone and rarely found in the mandible. Primary involvement of
      the mandible with MFH is an unusual presentation. A case of malignant fibrous
      histiocytoma, which posed a diagnostic difficulty, is presented here.

PMID- 23139507
TI  - Single layer closure of palatal fistula using anteriorly based dorsal tongue
      flap.
AB  - Palatal fistulas are the common complications seen after cleft palate repair.
      Small fistula may be asymptomatic, the large ones produce various symptoms
      including regurgitation of fluids into nasal cavity and interference with normal
      speech. Although small fistulas can be successfully treated with local flaps such
      as palatal or buccal mucosal flaps, large fistulas pose difficulty. Because of
      rich blood supply, tongue is a suitable and convenient source of large flap. The
      anterior based dorsal tongue flap is a safe and effective method for closure of
      relatively large recurrent palatal fistula with out any functional impairment of
      donor site. This article describes one such case treated by single layer closure
      using anteriorly based tongue flap with excellent outcome.

PMID- 23139508
TI  - Osseotite implants inserted into fresh frozen bone grafts.
AB  - BACKGROUND: In the last decade, several investigators have reported that double
      etched implants have achieved excellent results. However, no report regarding
      double etched implants inserted into fresh frozen bone is available. AIMS: We
      planned to perform a retrospective study on double etched implants inserted into
      fresh frozen bone grafts. SETTING AND DESIGN: 28 patients (17 females and 11
      males with a median age of 52 years) were operated on and 114 double etched
      implants inserted. Implant diameter and length ranged from 3.25 to 5.0 mm and
      from 10.0 to 15 mm, respectively. Implants were inserted to replace 14 incisors,
      5 cuspids, 47 premolars and 48 molars. RESULTS: Since only 4 out of 114 implants
      were lost (i.e. Survival Rate SVR = 96.5%) and no statistical differences were
      detected among the studied variables. The type of prosthetic restoration (i.e.
      fixed prostheses) correlated with a statistically significant lower delta Implant
      Abutment Junction (i.e. reduced crestal bone loss) and thus a better clinical
      outcome. CONCLUSION: Double etched implants inserted into fresh frozen bone had a
      high survival and success rate similar to those reported in previous studies of
      two-stage procedures in non-grafted bone, although a higher marginal bone loss
      has to be expected when removable prosthetic restorations are used.

PMID- 23139509
TI  - Histological significance of p53 gene expression in squamous cell carcinoma of
      the buccal mucosa.
AB  - INTRODUCTION: Oral Squamous Cell Carcinoma (SCC) results from genetic mutations
      which activate the oncogenes and inactivate the tumor suppressor gene namely
      TP53. Despite the use of multimodality treatments the prognosis of oral SCC has
      not changed significantly. PURPOSE: To evaluate 1) if there is any correlation
      between the two prognostic indicators i.e. p53 over expression and histological
      grade of the tumor 2) if any of the parameters of histological grading correlate
      significantly with p53 over expression. This information would help in
      understanding the exact role of TP53 gene mutation in cellular progression of
      oral SCC. METHOD: Study was conducted on 90 resected specimens of Stage IV SCC of
      buccal mucosa. Slides from these specimens were evaluated for histological
      grading by Anneroth's method and p53 over expression by Immunohistochemistry.
      RESULTS: Statistically significant co-relation was seen between the total
      histological grade and p53 over expression. Also 4 individual histological
      parameters which indicated high cellular turnover were also significantly
      associated with p53 over expression. CONCLUSION: TP53 mutation histologically
      signifies an early event in cellular progression of oral SCC.

PMID- 23139510
TI  - Use of recombinant human Bone Morphogenetic Protein (rhBMP-2) in reconstruction
      of maxillary alveolar clefts.
AB  - BACKGROUND: Use of rhBMP2 has been demonstrated to be an ideal bone
      reconstructive material for alveolar clefts. There is a lack of such studies from
      Indian cleft patients. AIM: To compare rhBMP2 alveolar cleft repair and iliac
      crest graft treated cases. MATERIALS AND METHOD: Retrospective analysis of rhBMP2
      alveolar cleft repair and iliac crest graft treated cases. PREDICTOR VARIABLES:
      Gender, type of surgery and type of cleft OUTCOME VARIABLES: Total surgery time,
      blood loss at surgical and harvest site, length of scar, number of days on
      antibiotics, serratiopeptidase and NSAIDS; sutured days, number of days to regain
      masticatory functions, pain VAS on 5th postoperative day and at harvest site on a
      scale of 10; duration of edema, number of working days lost, time until child
      could walk 'normally'; mean efficiency of bone deposition. STATISTICS:
      Descriptive, paired 't' test, one way ANOVA  RESULTS: Difference between rhBMP2
      and iliac crest graft treated cases in terms of antibiotic use, serratopeptidase,
      NSAIDS, pain at surgical site, edema, number of working lost for attendees and
      number of days to walk unaided were statistically significant. The mean length of
      surgery for unilateral cases was 87.60 minutes whereas it was 108.75 minutes for
      bilateral cases (p=0.003). The mean efficiency of bone deposition as revealed
      loss in radiolucency for rhBMP2 treated cases was 91.74% whereas iliac crest
      graft cases showed a 87.96% (p=0.006). DISCUSSION: It is evident that one has to
      reject null hypothesis in favor of the alternate hypothesis. The rhBMP2 is better
      than the conventional gold standard of iliac crest graft for restoration of
      maxillary alveolar clefts in terms of considered surgical, post surgical and
      radiographic planimetry parameters. CONCLUSION: Sparing children from the
      procedure of iliac crest harvesting is by itself a compelling reason to favor
      rhBMP2 use. It avoids the unnecessary surgery, loss of blood and postoperative
      morbidity of iliac crest harvesting.

PMID- 23139511
TI  - Maxillary arch width in unoperated adult of the unilateral cleft lip and alveolus
      patients.
AB  - BACKGROUND: The transversal measurement on the dento-alveolar fragments of the
      maxilla, in the unoperated adult patients with unilateral cleft lip and alveolus
      are rare and have not been well documented and archived in the scientific
      journals. The effect of the congenital malformation is obvious in the Unilateral
      Cleft Lip and Alveolus (UCLA) patients and is well documented. OBJECTIVES: The
      aim of this study is to investigate whether there are any influences of the final
      transversal development of the maxilla based on the location and extent of the
      defect in patients with UCLA. METHODS: 168 adult unoperated UCLA patients (study
      group) and 24 non cleft patients (control group) participated in this study.
      Plaster of Paris (POP) casts were made of the maxillary dentition and mesurement
      were taken using coordinate measuring machine (CCM) (Zeiss Numere, Carl Zeiss,
      Stuttgart, Germany). RESULT: The mean values of maxillary transverse measurement
      of first premolar through the second molar of the UCLA and control group patients
      showed no statistically significant difference. The inter-canine distance was
      significantly smaller in the UCLA patients than non-cleft patients CONCLUSIONS:
      The maxillary inter-canine distance in untreated UCLA patients were significantly
      different from that of non cleft patients. There is narrow and constricted
      maxillary growth in UCLA patients causing maxillary morphological changes and
      cosmetic facial changes.

PMID- 23139512
TI  - A comparative study between 0.5% centbucridine HCl and 2% lignocaine HCl with
      adrenaline (1:2,00,000).
AB  - Even today the ability to provide the patient with clinically adequate pain
      control with minimum systemic side effects is one of the major concerns all over
      the world. Lignocaine, the most commonly used local anesthetic agent in oral
      surgery due to its rapid onset & reasonably good potency, does not have adequate
      duration of action, unless used with Adrenaline, a drug known for its
      cardiovascular effects. Centbucridine, a non-ester, non-amide group local
      anesthetic agent developed in India at C D R I Lucknow, has advantage of inherent
      vasoconstrictor property. This study was planned to compare 0.5% Centbucridine
      and 2% Lignocaine with Adrenaline, in exodontia patients. The results were
      recorded for their efficacy and C V S action and statistically analyzed.
      Centbucridine was found to be an ideal local anesthetic agent with no effects on
      cardiovascular parameters and exhibiting a sufficient degree of local anesthetic
      activity suitable for use in routine minor surgery cases. This will be
      advantageous where Adrenaline is absolutely contraindicated due to systemic
      problems.

PMID- 23139513
TI  - Assessment of shoulder function after functional neck dissection and selective
      neck dissection (Levels I, II, III) in patients with carcinoma of tongue: a
      comparative study.
AB  - BACKGROUND AND OBJECTIVES: To compare shoulder function with respect to pain and
      disability in patients who have undergone nerve sparing neck dissection i.e.
      selective neck dissection (levels I, II, III) and functional neck dissection as a
      part of their treatment modality for carcinoma tongue on a follow up of minimum
      six months. MATERIAL AND METHODS: A total of 100 patients were selected for this
      study. 50 patients who had undergone selective neck dissection (levels I, II,
      III) and 50 who underwent functional neck dissection as a part of their treatment
      modality for squamous cell carcinoma of the tongue from January 2005 to January
      2007 were asked to participate in this study. A standardized questionnaire was
      used to assess pain and disability. Pain and disability scores were then compared
      between the two nerve sparing dissections. RESULTS: 100% of the patients in
      Selective Neck Dissection (SND) (levels I, II, III) group and in Functional Neck
      Dissection (FND) groups complained of pain. Though there is pain present in both
      the treatment groups, no significant difference in the pain values was found
      between FND and SND (levels I, II, III) in any of the pain parameters. Disability
      was present in both the treatment groups. However patients who have undergone FND
      had significantly higher severity of disability when compared to SND (levels I,
      II, III) especially during activities which involve shoulder abduction like
      dressing, doing heavy household work, hair wash and washing clothes/dishes (5.18,
      5.22, 5.5, 4.88 in FND and 2.26, 4.08, 4.58, 2.2 in SND (levels I, II, III)
      respectively. Disability perceived during other activities like doing heavy
      household and facial care was 2.08 and 1.84 in both the treatment groups
      respectively. INTERPRETATION AND CONCLUSION: Degree of shoulder morbidity is much
      higher in patients who have undergone FND as compared to SND (levels I, II, III)
      as a treatment modality for carcinoma tongue, even though both the treatment
      options are nerve preserving.

PMID- 23139514
TI  - Hypercalcemia in patients of oral squamous cell carcinoma.
AB  - PURPOSE: This study was performed to measure the total and ionic serum calcium
      levels and incidence of hypercalcemia in patients with Oral Squamous Cell
      Carcinoma (OSCC) and its clinical significance and relevance. MATERIALS AND
      METHODS: A randomly selected sample of seventy patients of histologically
      confirmed Oral Squamous Cell Carcinoma (OSCC) at any of the standard clinical
      stages were included. Fasting blood samples were obtained for measuring serum
      calcium levels. The elevated values of serum calcium levels were correlated with
      clinical features of hypercalcemia to draw inference. RESULTS: Total serum
      calcium was found to be elevated in 12 patients (17.4%) and serum ionic calcium
      was elevated in 3 patients (4.29%). CONCLUSION: The data suggests that
      hypercalcemia occurred in advanced stages of oral squamous cell carcinoma and its
      management may be relevant in providing terminal care and prolonging the life
      span of the patients.

PMID- 23139515
TI  - Mandibular third molar and inferior alveolar canal.
AB  - PURPOSE: The purpose of this study was to determine the incidence of Inferior
      Alveolar Nerve (IAN) damage after surgical removal of lower third molars, to
      identify the cause and to construct a predictive model to assess the risk of IAN
      injury. MATERIALS AND METHODS: Patients were selected from the out patient
      department after proper clinical and radiological evaluation of mandibular third
      molars. 50 mandibular third molars of 50 different patients were removed under
      local anaesthesia. Standardized data collection including the patient's name,
      age, gender, proximity of inferior alveolar nerve were recorded. RESULTS: A total
      6% of the operated sides demonstrated impairment of labial sensation and vast
      majority of these disturbances subsided completely within six weeks. CONCLUSION:
      For IAN we found Patient's age, the development of roots, the degree of impaction
      and the radiographic position of the nerve canal to be significantly correlated
      to sensory deficit.

PMID- 23139516
TI  - Mandibular third molars as a risk factor for angle fractures: a retrospective
      study.
AB  - INTRODUCTION: Anecdotal reports suggest that the presence of mandibular third
      molars predispose the mandible to angle fractures. The purpose of this study was
      to evaluate the presence of mandibular third molars as a risk factor for angle
      fractures in patients with fractured mandibles. MATERIALS AND METHOD: A
      retrospective study was designed comprising of patients admitted for treatment of
      mandibular fractures between January 2006 and January 2009. Data sources were the
      patients' medical records and radiographs. The predictor variables were the
      presence and position of third molar. Third molar position was grouped into 9
      categories based on the Winter's and Pell & Gregory classification. The outcome
      variable was the presence of an angle fracture. Other study variables included
      age, sex, race and mechanism of injury, associated fractures and fracture
      location. RESULTS: Of the 136 patients with mandibular third molars, 49 cases had
      angle fractures. Of the 18 patients without mandibular third molars, 03 had angle
      fractures. CONCLUSION: The results of this study demonstrate that patients with
      fractured mandibles and mandibular third molars are nearly 2.2 times more likely
      to have an angle fracture than patients without mandibular third molars.

PMID- 23139517
TI  - A retrospective analysis of 189 patients of maxillofacial injuries presenting to
      a tertiary care hospital in Punjab, India.
AB  - INTRODUCTION: Maxillofacial injuries form a major aspect of trauma management in
      trauma centers. Prompt diagnosis and management is needed to provide better
      quality of life and cosmetic results as compared to delayed interventions.
      MATERIAL AND METHODS: We present a retrospective study of 189 patients of
      complex, operable maxillofacial injury with an analysis of patients'; age and
      gender, mode of injury, vehicle details and associated injuries along with the
      maxillofacial injuries admitted in a tertiary care hospital in Northern India
      over one year. RESULTS: Maximum patients were in the age group of 21-30, a decade
      early as compared to other figures, with fractures of zygoma being predominant
      associated with head injury as the commonest comorbid condition. Motorized two
      wheelers were the leading cause with more than 75% patients driving at the time
      of injury. Majority of the injuries were not singular and in concordance with the
      literature men were the most affected. DISCUSSION: Motor vehicle accident is the
      most common cause for maxillofacial injury worldwide. Being a referral hospital
      the number of patients were low but the complexity was high with a reverse trend
      towards the type of injuries seen and the ones found in community hospitals. The
      stand alone factor of this study with respect to the other publications is the
      presentation of the associated symptom complex with the specified fracture and
      the type, number and rotation of fracture segments with each facial bone
      fracture; the location of the patient at the time of impact in the vehicle, type
      of vehicle and the associated injuries.

PMID- 23139518
TI  - Indications for removal of impacted mandibular third molars: a single
      institutional experience in Libya.
AB  - AIMS: To investigate the various indications for the removal of impacted lower
      third molars in a dental school in Libya. METHODS: The records of all patients
      who underwent a surgical removal of a lower third molar over a 3 year period were
      reviewed retrospectively. The indications for removal were classified into 10
      groups. Radiographs were also studied to determine angular position as well as
      pathologies associated with such teeth. Age, gender and chief complaint of all
      patients were recorded. RESULTS: The results were based on the data of 439
      patients who had their third molars removed (Male-183; Female-256). 61% of
      patients were in the age groups 15-24. Recurrent pericoronitis was found to be
      the most common indication recorded (54%), followed by pulpitis/caries of the
      3rd/2nd molar (31%). Orthodontic reasons (2%) and cysts/tumours (5%) were among
      the other indications recorded. Pain and tenderness was recorded as the most
      common symptom. The relative absence of prophylactic removal as an indication
      could be attributed to socioeconomic and logistic reasons. CONCLUSION: Awareness
      of the indications for removal of impacted lower third molars will help in
      management of such patients. A fear of dentistry appears to be responsible for
      patients reporting to the dental surgeon only when symptoms occur. Patients
      generally do not agree to prophylactic removal of lower third molars. Removal of
      only symptomatic lower third molars seems to be the logical choice in view of
      financial and manpower constraints in developing nations.

PMID- 23139519
TI  - Surgical treatment of maxillary transverse deficiency: retrospective study of 14
      patients.
AB  - INTRODUCTION: The diversity of the proposed techniques in the treatment of
      maxillary transverse deficiency in adults reflects the conflicting opinions about
      the primary area of resistance to maxillary expansion in the craniofacial
      skeleton. In order to evaluate the efficiency of the surgical expansion in which
      no osteotomies of the pterygomaxillary junction were made, we have carried out a
      retrospective study with 14 patients with maxillary transverse deficiency, who
      were treated from 2003 to 2006. MATERIAL AND METHODS: In the study, models were
      made prior to and after surgery, and the intercanine and intermolar distances and
      the improvement of the interocclusal relationships were analyzed. Breathing
      function and the complications that occurred during and after the surgeries were
      also analyzed. RESULTS: All expansions were carried out according to pre-surgical
      planning so that expansion completely corrected the crossbite, resulting in the
      desired final occlusion for all patients. Intraoperative complications were
      limited to one Hyrax appliance deformation. Two patients had minor postoperative
      complications that included wound dehiscence and pain. Improvements in nasal
      breathing were observed in all patients that complained of breathing problems
      prior to the surgery. CONCLUSION: The satisfactory results obtained turns the
      surgical protocol described in this study recommended for the treatment of
      maxillary transverse deficiency in adults. Importantly, we found that
      pterygomaxillary osteotomy is not essential for maxillary expansion. The
      morbidity of the procedure was low with fairly minor complications, and
      surgically assisted rapid maxillary expansion was shown to improve nasal
      breathing.

PMID- 23139520
TI  - Use of a modified epidural catheter for analgesia after iliac crest bone
      procurement.
AB  - BACKGROUND AND OBJECTIVES: Autogenous bone grafting is the gold standard
      procedure for various maxillofacial defects which needs surgical correction and
      anterior iliac crest is the most common site of harvest. Immediate postoperative
      pain at the harvested site is a major morbidity associated with it. The aim of
      the study was to assess the immediate postoperative pain control at the iliac
      crest graft harvested site by placing an epidural catheter in the incision wound
      and continuously infiltrating bupivacaine 0.25% at regular intervals. MATERIALS
      AND METHODS: Twenty patients requiring autogenous bone grafting for large
      maxillofacial defects were chosen for the study. They were divided randomly into
      two groups of ten each. Group 1 patients were placed with epidural catheter in
      the incision wound at iliac crest harvested site and group 2 patients did not
      receive epidural catheter. Continuous infiltration of long acting amide local
      anesthetic (Bupivacaine) was given to group 1 patients on the postoperative day.
      Both group 1 & group 2 patients received parenteral analgesic Diclofenac sodium
      75mg intramuscularly. Pain at the iliac crest and maxillofacial area was assessed
      by VAS scale. Also the time of ambulation of the patient was noted. These
      variables were compared statistically. RESULTS: The observed findings were
      statistically analyzed. Group 1 patients showed significant pain relief at the
      graft harvested site as compared to group 2 patients. Also the patients in group
      1 were ambulated early as compared to group 2 patients. INTERPRETATION AND
      CONCLUSION: It was concluded that by placing epidural catheter at the incision
      wound and continuously infiltrating with bupivacaine 0.25% at iliac crest
      harvested site at regular intervals effectively controls the immediate acute pain
      postoperatively and the patient can be ambulated and brought back to normal
      routine early.

PMID- 23139521
TI  - Changes in quality of life after surgical removal of impacted mandibular third
      molar teeth.
AB  - BACKGROUND: The decision to get impacted teeth removed is not straightforward
      because of the concerns about its possible outcome. Assessment of quality of life
      is now regarded as an essential component for assessing outcomes of dental health
      care. The purpose of this paper is to assess the effect of impacted third molar
      teeth surgery on a number of health related outcomes. PATIENTS AND METHODS: A
      total of 72 patients undergoing surgical removal of their unilateral impacted
      mandibular third molar teeth were recruited to participate in this study.
      Patients were asked to complete two questionnaires, 14-item Oral Health Impact
      Profile (OHIP-14) and the 16-item UK Oral Health related Quality of Life measure
      questionnaire (OHQOLUK-16) daily for one week following surgery. RESULTS: There
      was significant decrease in the mean OHQOLUK-16 score and OHIP-14 scores for the
      first five postoperative days. There were no significant differences in changes
      in the mean OHIP-14 scores or OHQOLUK-16 scores on postoperative day 6 and 7.
      CONCLUSION: There was a significant deterioration in oral health related quality
      of life in the immediate postoperative period, which slowly returned to
      preoperative level by day 6. This information may be useful in creating realistic
      expectation for patients who are considering third molar surgery.

PMID- 23139522
TI  - Use of collagen in extraoral wounds.
AB  - The basic fundamental elements that collagen bring into the wound activity are
      its hemostatic effect, its interaction with platelets and interaction with
      fibronection, increase in fluid exudates, increase in cellular components
      (macrophages) and support for fibroblastic proliferation into wound activity. In
      this way collagen plays a significant parts in almost every function of the body.
      Previously broad use of collagen was stifled because of cost, recent advances
      made it possible to develop cost effective collagen. In this study twenty
      patients of maxillofacial wounds were treated with the use of collagen. The
      results were satisfactory without any significant complication.

PMID- 23139523
TI  - Efficacy of two point rigid internal fixation in the management of zygomatic
      complex fracture.
AB  - PURPOSE: To evaluate the efficacy of two point rigid internal fixation in the
      immobilization of zygomatic complex fractures. PATIENTS AND METHODS: 30 patients
      with zygomatic complex fractures were managed by open reduction and internal
      fixation using titanium mini bone plate screws at the frontozygomatic and
      zygomatic buttress region. This prospective study was carried out at the
      Department of Oral & Maxillofacial Surgery, Armed Forces Medical College (AFMC),
      Pune, India between 1st August 2005 to 1st August 2007. Isolated unilateral
      zygomatic complex fractures of less than six weeks duration were included in the
      study. RESULT: Clinically and radiologically satisfactory results were achieved
      in all 30 patients using two point rigid internal fixation at the frontozygomatic
      and zygomatic buttress region of zygomatic complex fracture. CONCLUSIONS: Stable
      fixation and immobilization of isolated zygomatic complex can be achieved with
      two point fixation using titanium mini bone plate and screws at the
      frontozygomatic and zygomatic buttress region of zygomatic complex fracture.
      Postoperative complications like scarring, ectropion and neurological deficit can
      be avoided by not using infraorbital rim as the third point of fixation.

PMID- 23139524
TI  - Evaluation of glutathione in oral squamous cell carcinoma.
AB  - PURPOSE: To estimate the RBC level of glutathione among oral squamous cell
      carcinoma cases and normal healthy individual. The study compares the pre and
      postoperative blood levels of glutathione in patients with oral squamous cell
      carcinoma. MATERIALS AND METHOD: In the present study a total of 45, age matched
      subjects were recruited. The 45 subjects were split into 15 subjects in control,
      30 clinically and histopathologically diagnosed cases of oral squamous cell
      carcinoma who had not received any prior treatment. RESULTS: A statistically
      significant difference of mean value of glutathione levels in RBC of the control
      group was found to be higher than that of oral squamous cell carcinoma patient
      group. A noticeable rise in glutathione concentration in RBC of oral squamous
      cell carcinoma towards normal was seen postoperatively, however these variations
      were not statistically significant. CONCLUSION: Pre and postoperatively a marked
      variation in levels of glutathione was observed. In addition, it was noticed that
      the levels tended to shift closer to control/normal values postoperatively. The
      value of glutathione as a prognostic marker could be ratified if the study was
      carried out on a larger scale over a sustained period of time.

PMID- 23139525
TI  - Free fibula flap in the reconstruction of mandible: a report of six cases.
AB  - The defects secondary to surgical ablation of the mandible have far reaching
      consequences. Speech, respiration, mastication, deglutition and cosmesis are
      severely affected. Restoring these functions is a challenging task. Till the late
      eighties, myocutaneous flaps were the rule for mandibular reconstruction and free
      bone was used to restore bony continuity.In spite of the result being predictable
      the outcome left much to be desired. There was also a fairly regular crop of
      complications. Acceptable dental rehabilitation was almost non-existent. With the
      introduction of free flaps as a consequence of the development of the operating
      microscope, the field of reconstruction was revolutionized.The fibular free flap
      is especially suited for mandibular reconstruction. It provides adequate bone to
      re-establish bony continuity and also allows for the placement of osseointegrated
      implants.Here we present six of our cases, which underwent mandibular
      reconstruction with free fibula flaps and the current thoughts in literature on
      the reconstruction of the mandible with this technique.

PMID- 23139526
TI  - 45,X/46,XY mosaicism and Oculo-Auriculo-Vertebral Spectrum following an IVF
      pregnancy: a report and a discussion of their interrelationships.
AB  - The aetiology of Oculo-Auriculo-Vertebral Spectrum (OAVS) is unkown. We report a
      case following a prenatal diagnosis of 45,X/46,XY mosaicism in a pregnancy
      achieved by In-Vitro Fertilization (IVF) and describe evidence for the
      interrelationships of these phenomena and multiple births. This report extends
      the phenotypes associated with prenatally diagnosed 45,X/46,XY mosaicism and
      supports the association of OAVS and IVF.

PMID- 23139527
TI  - Schwannomas of the head and neck: a case series.
AB  - Schwannomas are relatively slow growing benign tumors of the nerve sheath with a
      well developed capsule. They can reach a considerable size. Typically, symptoms
      of schwannomas are based on the affected nerve. We present four cases of this
      tumor that occurred in the head and neck. The differential diagnosis of small
      painless nodules in head and neck must include schwannomas as it is likely that
      nerve sheath neoplasms are more common than previously reported. However, due to
      benign nature and low recurrence prognosis is excellent.

PMID- 23139528
TI  - Malignant melanoma of lingual gingiva with ipsilateral submandibular lymph node
      metastasis: a case report.
AB  - Malignant melanoma is a neoplasm of epidermal melanocytes. It is one of the most
      biologically unpredictable and deadly of all human neoplasms. However, malignant
      melanoma in the oral cavity is a rare malignancy, accounting for 0.2% to 8% of
      all melanomas. It has a grave prognosis, with a 5 year survival of 10-20%. We
      present a case of malignant melanoma of lingual gingiva of left mandibular molars
      with ipsilateral submandibular lymph node metastasis. We performed peripheral
      osteotomy of primary lesion followed by modified radical neck dissection by
      sparing internal jugular vein and patient had received postoperative
      radiotherapy.

PMID- 23139529
TI  - Chondroblastic osteosarcoma of maxilla: a case report and review of literature.
AB  - Craniofacial osteosarcoma is a relatively rare entity comprising about 6.5-7% of
      all osteosarcomas, whereas it is reported to be one of the most common
      malignancies of long bones. We present a case of chondroblastic variant of
      osteosarcoma (COS) of the maxilla in an 18 year-old-girl. She was treated with a
      subtotal maxillectomy and later referred for adjuvant chemotherapy. The relevant
      review of literature with regard to clinical, radiographic findings,
      histopathological similarities to Chondrosarcoma (CS), role of
      Immunohistochemistry (IHC) and management modalities of Osteosarcoma of jaw bones
      (OSJ) in comparison with Osteosarcoma of the long bones (OSL) are being presented
      in this report.

PMID- 23139530
TI  - Granular cell - Peripheral ameloblastoma: a rare variant.
AB  - Ameloblastoma is an epithelial odontogenic tumour of the jaw and exhibits diverse
      microscopic patterns which occurs either singly or in combination with other
      patterns. Peripheral ameloblastoma is a rare odontogenic soft tissue tumor,
      derived from epithelial and/or mesenchymal elements being part of the tooth
      forming apparatus. The lesions responsible for approximately 1% to 5% of all
      cases of ameloblastoma affecting alveolar mucosa and gingiva occurring mainly, in
      the middle age. This article describes a case of peripheral ameloblastoma
      affecting a 35-year-old female. The lesion was located in the right buccal space.
      The occurrence and pathogenesis of peripheral ameloblastomas in general, are
      reviewed. The tumour was excised and no recurrence has been observed after twenty
      four months of surgery.

PMID- 23139531
TI  - Angioleiomyoma of cheek: report of two cases.
AB  - Leiomyomas are benign tumors derived from smooth muscle that most commonly arise
      in the uterus, followed by the gastrointestinal tract and subcutaneous tissues.
      Deep presentations are typically asymptomatic unless they achieve substantial
      size, whereas subcutaneous presentations may be associated with considerable
      local tenderness and pain, in addition to alteration of the overlying skin color.
      The highest incidence occurs between 40 and 49 years of age in the orofacial
      region, the angiomyoma is the predominant subtype, representing nearly 75% of all
      reported cases [1]. Oral leiomyomas are considered uncommon neoplasms, accounting
      for about 0.065% [2]. Despite the rather characteristic histopathologic features
      of the leiomyoma, a definitive diagnosis often depends on the confirmation of
      smooth muscle origin by immunohistochemical studies. We report two cases of
      angioleiomyoma of cheek with their clinical presentation histopathological
      features and surgical techniques employed. No recurrence has been seen as of yet
      in both of our cases.

PMID- 23139532
TI  - Efficacy of platelet rich plasma in bone regeneration after surgical removal of
      impacted bilateral mandibular third molars: pilot study.
AB  - PURPOSE: This study was done to assess the efficacy of platelet rich plasma (PRP)
      in bone regeneration. MATERIALS AND METHODS: 20 patients having bilateral
      mandibular third molar impaction with similar angulations were included in the
      present study. The extraction socket was packed with PRP on one side and the
      other side was sutured without PRP. The bone density of both extraction sockets
      were evaluated radiographically using gray level histogram and compared
      periodically. Postoperative pain and edema were also assessed. RESULTS: The
      result of the study shows rapid bone regeneration in the extraction socket
      treated with PRP when compared with the socket without PRP. Also there was less
      postoperative discomfort on the PRP treated side. CONCLUSION: Within the limits
      of the present study it can be concluded that usage of PRP expedites bone
      regeneration, and reduces postoperative complications.

PMID- 23139533
TI  - Potential for osseous regeneration of platelet rich plasma: a comparitive study
      in mandibular third molar sockets.
AB  - PURPOSE: To evaluate the efficacy of autologous platelet-rich plasma in soft
      tissue healing & bone regeneration in mandibular third molar extraction socket.
      METHODS: The study was conducted in 10 patients visiting the outpatient
      Department of Oral & Maxillofacial Surgery, requiring extraction of bilateral
      mandibular third molars. Following extraction, autologous Platelet Rich Plasma
      (PRP) was placed in one extraction socket, the other socket was studied as the
      control site with no PRP. The patients were assessed for postoperative pain, soft
      tissue healing, bone blending and trabecular formation. Radiological assessment
      of the extraction site was done for a period of 4 months to evaluate the change
      in bone density. RESULTS: Pain was less in the study site compared to control
      site, soft tissue healing was better in study site. Evaluation for bone blending
      and trabecular bone formation started earlier in PRP site compared to control,
      non PRP site. The evaluation of bone density by radiological assessment showed
      the grey level values calculated after 4 months at the PRP site were
      comparatively higher than the average baseline value of bone density at
      extraction site in control site. CONCLUSION: The study showed that autologous PRP
      is biocompatible and has significantly improved soft tissue healing, bone
      regeneration and increase in bone density in extraction sockets. However a more
      elaborate study with a larger number of clinical cases is essential to be more
      conclusive regarding its efficacy.

PMID- 23139534
TI  - Multiple spurting test in microsurgical reconstruction of the lower extremities.
AB  - Appropriate recipient artery is essential for the success of free flap
      reconstruction, however the selection could be difficult in a traumatized lower
      extremity. To detect unnoticed damage of the recipient artery, vascular integrity
      should be verified. For that purpose, we propose a simple and effective
      evaluation method, called Multiple Spurting Test (MST) this test esteems the
      dynamic status of the recipient arteries by measuring the length of arterial
      spurting. All the microsurgeons usually do something like MST: but it is not a
      standardized test yet.This study analyzed if this test could be a practical
      method in searching a safe recipient artery during microsurgical reconstruction
      of lower extremity. MST was employed in 163 flaps, all for lower extremity
      reconstruction. Fifteen flaps were re-explored in this series. Six of them had
      arterial problems, three in Anterior Tibial Artery (ATA), two in Posterior Tibial
      Artery (PTA) and one in Sural Artery (SA). The overall series' re-exploration
      rate, due to different complications, was 7% when ATA has been the recipient
      vessel, 7.6% with PTA and 30.7% with SA. Both ATA and PTA found equally reliable
      after examination with MST. We do believe that MST can effectively decrease the
      incidence of arterial complications and flap failure. Using this method, it is
      easier to choose a safe recipient artery for revascularization.

PMID- 23139535
TI  - A retrospective study of ranula in two centres in Malaysia.
AB  - INTRODUCTION: Ranula is a mucous extravasation cyst which occurs as a result of
      trauma or obstruction of the sublingual or minor salivary gland or the duct
      itself. PATIENTS AND RESULTS: 14 patients were seen at Universiti Kebangsaan
      Malaysia Medical Centre, Kuala Lumpur and Hospital Tunku Ampuan Afzan, Kuantan,
      Malaysia between 2000 to 2006. There were six cases of intra-oral ranula and
      eight plunging ranula. Twelve patients underwent surgical intervention while two
      refused surgery. Four patients (33.3%) from those who had surgical intervention
      returned with recurrence; two (16.7%) had marsupialization and the other two
      (16.7%) had excision of the pseudocyst intraorally. CONCLUSION: Excision and
      marsupialization remain as the treatment of choice in our centres.

PMID- 23139536
TI  - Time lapse from the occurrence of trauma to the definitive management of
      mandibular fractures: a retrospective study.
AB  - The surgical management of maxillofacial trauma has come a long way in the last
      four millennia and without doubt will go further. The principles are not new but
      the interpretation constantly changes. A retrospective review of 52 inpatient
      records of mandibular fracture patients was done for the period 1 January 2003 to
      30 June 2005.

PMID- 23139537
TI  - Endosseous alveolar distractor (LEADTM) in the management of residual alveolar
      ridge resorption.
AB  - BACKGROUND: Lack of sufficient alveolar bone height or width is one of the most
      frequent problems in the dental rehabilitation of the edentulous patient.
      METHODS: A prospective study to evaluate the efficacy of an endosseous alveolar
      distractor (LEADTM) in managing residual alveolar ridge resorption was carried
      out. The complications related to the surgical procedure and the quantitative
      changes in the regenerate over a 6 month period following distraction were
      studied in 13 cases with alveolar ridge atrophy. RESULT: Desired ridge
      augmentation was achieved in 11 cases. In 2 cases the distraction failed. Some
      unusual complications were encountered. CONCLUSION: The LEADTM alveolar
      distractor produces consistent augmentation of the alveolar bone but is
      confronted with stability issues.

PMID- 23139538
TI  - In vitro evaluation of microbiological flora of orofacial infections.
AB  - OBJECTIVE: To assess the most common micro-organisms causing odontogenic
      infections and their antimicrobial susceptibility. METHODS: The study was
      conducted in 80 patients with orofacial infection. The pus sample was collected,
      cultured (aerobically and anaerobically) and stained for morphological study of
      the isolates. Antibiotic sensitivity test for the isolates were performed.
      RESULTS: A total of 109 micro-organisms were isolated, no pathogenic organism
      were isolated in 3 cases. Out of 109 micro-organism isolated, 107 bacteria and 2
      fungi were identified. Pure aerobes were identified in 28(35%) of cases, pure
      anaerobes in 18(22.5%), mixed aerobes and anaerobes in 10(12.5%), mixed aerobes
      in 15(18.75%) and mixed anaerobes were isolated in 6(7.5%) cases. Among the
      entire pure gram positive isolates, ofloxacin was the most sensitive drug 83.33%
      followed by ciprofloxacin 76.2% and sparfloxacin 76.2%. The most resistant drugs
      were amoxicillin (92.85%) and ampicillin (92.85%). Cefotaxime was found sensitive
      in 75% of pure gram negative isolates. CONCLUSION: Ofloxacin was the most
      sensitive drug followed by ciprofloxacin and sparfloxacin for pure gram positive
      isolates. The most resistant drugs were amoxicillin and ampicillin. The gram
      negative colonies were sensitive to Cefotaxime.

PMID- 23139539
TI  - 3D finite element analysis to detect stress distribution: spiral family implants.
AB  - AIM: Spiral family implants are a root-form fixtures with increasing thickness of
      tread. This characteristic gives a self-tapping and self-condensing bone
      properties to implants. To study spiral family implant inserted in different bone
      quality and connected with abutments of different angulations a Finite Element
      Analysis (FEA) was performed. Once drawn the systems that were object of the
      study by CAD (Computer Aided Design), the FEA discretized solids composing the
      system in many infinitesimal little elementary solids defined finite elements.
      This lead to a mesh formation where the single finite elements were connected
      among them by nodes. For the 3 units bone-implant-abutments several thousand of
      tetrahedral elements having 10 parabolic nodes were employed. MATERIALS AND
      METHODS: The biomechanical behaviour of 4.2 mm * 13 mm dental implants,
      connecting screw, straight and 15 degrees  and 25 degrees  angulated abutment
      subjected to static loads, in contact with high and poor bone quality was
      evaluated by FEA. A double system was analyzed: a) FY strength acting along Y
      axis and having 200 N intensity; b) FY and FZ couple of strengths applied along Y
      and Z directions and having respectively 200N and 140N intensity. The materials
      were considered as homogeneous, linear and isotropic. Then the FEA simulation was
      performed hypothesizing a linearity between loads and deformations. RESULTS: The
      lowest stress value was found in the system composed by implants and straight
      abutments loaded with a vertical strength, while the highest stress value were
      found in implants and 15 degrees  angulated abutment loaded with a angulated
      strength. In addition, the lower is the bone quality (i.e. D4) the higher is the
      distribution of the stress within the bone. CONCLUSION: Spiral family implants
      can be used successfully in low bone quality but a straight force is recommended.

PMID- 23139540
TI  - Teeth position, eruption and temporomandibular joint ankylosis.
AB  - BACKGROUND: Abnormality of tooth formation and position is often encountered in
      mandibular growth with TMJ ankylosis resulting from mandibular condylar
      fractures. Literature is scarce is in this phenomenon and remains largely
      anecdotal AIM AND OBJECTIVES: To study the relationship of teeth formation and
      position, to the age at which trauma occurred resulting in a mandibular
      unilateral condylar ankylosis. MATERIAL AND METHODS: Retrospective qualitative
      analysis of orthopantomograms from archives of cases diagnosed with mandibular
      unilateral condylar ankylosis. PREDICTOR VARIABLE: Position of mandibular 2nd
      premolar, 1st, 2nd, 3rd molar, age at which trauma occurred OUTCOME VARIABLES:
      Degree of impaction or normally erupted RESULT: In the ipsilateral side of
      trauma, 66.67% of 2nd premolars, 44.4% of 1st molar, 88.89% of 2nd molar and
      44.4% of 3rd molars were abnormal, while in the contralateral normal side and
      22.2% of 3rd molar exhibited abnormality. DISCUSSION: In mandible, post condylar
      fracture growth brings about deficiency in the length of corpus. The deficiency
      of length brings teeth abnormality - in terms of its growth and eruption. The
      abnormality in the position of teeth is related to the age at which trauma
      occurred. CONCLUSION: Evidence of tooth formation and eruption being affected in
      mandibular growth after mandibular condylar fractures and this phenomenon appears
      to be age related.

PMID- 23139541
TI  - Evaluation of metal release and local tissue response to indigenous stainless
      steel miniplates used in facial fractures.
AB  - The issue of metal release from stainless steel bone plates has gained
      considerable momentum advocating the removal of stainless steel miniplates after
      healing of fracture. So far no study has been published in the literature
      regarding metal release with the indigenously manufactured stainless steel
      miniplates.Objective Aim of the study was to find any pathological changes at
      cellular and ultracellular levels and metal particles in the soft tissue
      surrounding the stainless steel miniplates.Method Retrieval of indigenous
      stainless steel implants, used in treatment of jaw fractures, samples of
      surrounding soft tissue were histopathologically assessed for tissue response as
      well as metal release, using light microscope and Transmitted Electron Microscope
      (TEM).Result Light microscopic examination revealed chronic inflammation in
      symptomatic cases, but TEM did not show any significant pathological alteration
      and metal deposits even in cases with clinically observed pigmentation. Short
      term (upto 1 year) retention of stainless steel mini plates will not cause any
      significant local complications.

PMID- 23139543
TI  - Accuracy of intraoperative frozensection in assessing margins in oral cancer
      resection.
AB  - OBJECTIVES: To study the accuracy of intraoperative frozen section diagnosis in
      assessing margins in oral cancer resection and to evaluate the role of frozen
      section diagnosis as a guide in resection of oral cancer lesions. PATIENTS AND
      METHODS: The fresh tissue samples from the margins of lesions of patient with
      preoperative diagnosis of oral squamous cell carcinoma were used. The frozen
      sections are prepared immediately and examined by oral pathologist for the study.
      The results of these sections were compared with the results of histologic
      findings obtained by routine paraffin embedded Haemotoxylin and eosin method.
      RESULTS: The total of 184 margins, from 47 patients were examined. 178 margins
      showed concordance with the permanent section of the same tissue sample (seven
      false negative and one false positive), an accuracy rate of 96.74%. CONCLUSION:
      Frozen section is a helpful tool in intraoperative decision making in indicated
      situation. The results are highly specific but only moderately sensitive. The
      surgeon and the pathologist must understand the limitations of frozen sections.

PMID- 23139544
TI  - Healing assessment of osseous defects of periapical lesions with use of freeze
      dried bone allograft.
AB  - OBJECTIVES: The aim of this study was to save endodontically failed teeth with
      periapical pathosis by surgery. Elimination of the periapical pathology and to
      evaluate the clinical and radiological efficiency of freeze dried bone allograft
      in bony defects. MATERIALS AND METHODS: Ten patients were included in this study
      with established periapical pathology with the need for periapical surgery after
      failed endodontic therapy. Surgery was decided after the cessation of acute
      symptoms. Patients on regular medications for known medical complications were
      excluded from the study. A full thickness flap or modified Leubke-ochsecnbein was
      raised depending upon the size and location of the lesion. Thorough periapical
      curettage was performed to remove the pathological tissue surrounding the apices
      and the root of the tooth. The graft material was mixed with patient's venous
      blood drawn earlier from a peripheral vein to make it more cohesive. The graft
      material mixed with blood was then carefully packed with light pressure into the
      defect. The flap was replaced. All the patients received broad spectrum
      antibiotics one day before and five days after surgery. The cases were followed
      up with clinical and radiological examination and were recalled at intervals of 1
      month, 3 months and 5 months postoperatively to assess the condition of the
      periapical area. RESULTS: In all the ten cases at the end of 1st month
      postoperatively a well defined border separating the host bone from the graft
      material indicating simultaneous resorption of the graft. This resorption
      continued at 3 months follow up indicating continued graft resorption and also
      increasing radioopacity, haziness indicating bone regeneration. Eight of the ten
      patients could be evaluated at the end of fifth month and radiographs showed
      increase in radioopacity and reduction in size of periapical radiolucency as well
      as normal trabecular pattern of the bone. CONCLUSION: The results demonstrate
      successful use of FDBA in the treatment of osseous defects of periapical lesions
      associated with failed endodontically treated teeth.

PMID- 23139545
TI  - Keloidoscope: in search for the ideal treatment of keloids.
AB  - Although keloids were recognised in the Smith Papyrus of ancient times, the
      precise definition, cause and management have remained elusive. Several forms of
      treatment have been used with varying success.Objectives This study assesses and
      compares the value of intralesional steroid (Triamcinolone acetonide 40mg/ml),
      cryotherapy and cryotherapy with intralesional steroid in the treatment of
      keloids.Methodology 33 patients were studied, 11 each in the three arms and the
      volume of the keloids was recorded using wax patterns of alginate impressions of
      the keloids to note the change in size postoperatively.Results The best average
      percentage response was observed is patients who received both Cryotherapy (CRY)
      and Intralesional Steroid (ILS) (69.02%) followed by patients who received only
      intralesional steroid (43.98%). Among the patients who received only cryotherapy,
      the average percentage response was only 39.24%. 72.73% patients who received
      intralesional steroid with cryotherapy showed more than 50% improvement (good
      response) while only 9.09% patients who received intralesional steroid alone and
      cryotherapy alone showed similar improvement.Conclusion In patients with keloids
      good response can be obtained with CRY with ILS as compared to ILS alone and CRY
      alone.

PMID- 23139542
TI  - Craniofacial surgery, from past pioneers to future promise.
AB  - OBJECTIVES: As a surgical subspecialty devoted to restoration of normal facial
      and calvarial anatomy, craniofacial surgeons must navigate the balance between
      pathologic states of bone excess and bone deficit. While current techniques
      employed take root in lessons learned from the success and failure of early
      pioneers, craniofacial surgery continues to evolve, and novel modalities will
      undoubtedly arise integrating past and present experiences with future promise to
      effectively treat craniofacial disorders. METHODS: This review provides an
      overview of current approaches in craniofacial surgery for treating states of
      bone excess and deficit, recent advances in our understanding of the molecular
      and cellular processes underlying craniosynostosis, a pathological state of bone
      excess, and current research efforts in cellular-based therapies for bone
      regeneration. RESULTS: The surgical treatment of bone excess and deficit has
      evolved to improve both the functional and morphological outcomes of affected
      patients. Recent progress in elucidating the molecular and cellular mechanisms
      governing bone formation will be instrumental for developing improved therapies
      for the treatment of pathological states of bone excess and deficit. CONCLUSIONS:
      While significant advances have been achieved in craniofacial surgery, improved
      strategies for addressing states of bone excess and bone deficit in the
      craniofacial region are needed. Investigations on the biomolecular events
      involved in craniosynostosis and cellular-based bone tissue engineering may soon
      be added to the armamentarium of surgeons treating craniofacial dysmorphologies.

PMID- 23139546
TI  - An effective intra-operative method to control bleeding from vessels medial to
      the temporomandibular joint.
AB  - The control of hemorrhage from the medial aspect of the TMJ can be troublesome
      and time-cosuming during ankylosis surgery. There could be a number of vessels
      which could lead to this inadvertent though sometimes unavoidable complication.
      We have found that simple compression against bone can be useful in controlling
      hemorrhage from this difficult to approach site. This short paper describes the
      technique which we follow in our unit for such situations.

PMID- 23139547
TI  - Temporomandibular joint interpositional gap arthroplasty under intravenous (I.V)
      conscious sedation.
AB  - Ankylosis may be defined as the fusion of joint surfaces. Temporomandibular joint
      (TMJ) ankylosis is a condition that may cause chewing, digestion, speech,
      esthetic and psychological disorders. It is a devastating disorder resulting in
      inability to open the mouth. As a result of this, General anaesthesia, is very
      difficult to administer because laryngeal inlet is not directly visualized. Even
      the blind nasal intubation is difficult because of small mandible and tongue fall
      following relaxation. There are various techniques to overcome these challenges.
      At times these techniques fail and tracheostomy has to be done. All the risks
      associated with difficult intubation, and general anaesthesia can be avoided if
      the surgery is done under conscious sedation. Conscious sedation, a simple but
      safe and effective method of anaesthesia is described here, which allows
      successful temporomandibular joint interpositional gap arthroplasty.

PMID- 23139548
TI  - The use of maxillomandibular fixation screws with essig wiring in the treatment
      of symphyseal fracture of deep bite patients.
AB  - Today, the use of the arch bars in the treatment of mandibular fractures is
      common [1]. But it has complications such as damaged teeth, periodontal tissue
      [2], risk of blood transmitted disease [3] and premature contact with maxillary
      incisor teeth in anterior deep bite occlusion. Many techniques are used for
      resolving these problems.In this paper, we describe the technique of using
      Maxillo-Mandibular Fixation Screws (MMFS) with essig wiring of anterior
      mandibular teeth in the management of symphyseal fracture of deep bite patients.

PMID- 23139549
TI  - Unusual causes of trismus: a report of two cases.
AB  - Chronic inability to achieve normal mouth opening can be a symptom of several
      diseases. Mostly the causes of inability to open mouth are articular and
      sometimes the cause may be extra-articular. In the two cases which are being
      reported in this article the causes of limited mouth opening are extra-articular
      and that too from rare pathologies, of which one case is of OKC of the coronoid
      process and the other case is of myositis ossificans of the buccinator and medial
      pterygoid muscle. Both the cases had adequate mouth opening both intraoperatively
      and at long term follow up.

PMID- 23139550
TI  - Massive osteolysis of hemimandible: a case report.
AB  - Massive osteolysis or Gorham's stout disease or phantom bone is a rare disorder
      which normally appears in adulthood with no specific predilection for any sex.
      Work to find out exact etiology of disorder has been done. But actual cause has
      not yet been found. Any of the bone could be involved in this disease. A
      clinical, radiographic and histological evaluation of massive osteolysis of
      mandible is presented and discussed.

PMID- 23139551
TI  - Condyloma acuminatum associated with odontogenic myxoma: a case report.
AB  - Condylomata acuminatum is a sexually transmitted infectious disease caused by
      human papiloma virus on the skin. The transmission is mainly by close contact
      with infected person and autoinoculation. In oral cavity the condition manifests
      as soft pink nodules which proliferate and coalesce rapidly to form diffuse
      papillomatous clusters of varying size. Odontogenic myxoma is a rare tumor of
      jaws which occurs in the tooth-bearing areas of the mandible and maxilla. It is
      an uncommon, benign, but locally aggressive neoplasm. This case report highlights
      a 17-year-old girl with two lesions in oral cavity with soft tissue growth on the
      palate which has been diagnosed as Condyloma Acuminatum, treated by surgical
      excision and a large swelling on the right side of the mandible in the same
      patient diagnosed as odontogenic myxoma where marginal resection was performed.

PMID- 23139552
TI  - Dermoid cyst of the floor of the mouth with abundant hair: a case report.
AB  - Dermoid cysts are developmental cysts and considered to develop from enslavement
      of epithelial debris in the midline during closure of the mandibular and hyoid
      brachial arches. These cysts are painless, slow growing and most commonly occur
      in young adults with no gender predilection. They are uncommon in the head and
      neck region. Oral dermoid cysts are found usually in the submental or sublingual
      triangle in variable relation to mylohyoid, geniohyoid, and genioglossus muscle.
      The cyst is lined by epidermis like epithelium and contains dermal adnexal
      structures in the cyst wall. We report a case of dermoid cyst arising in the
      sublingual region of a young adult male with abundance of hair which is rare
      finding.

PMID- 23139553
TI  - Lefort-2 osteotomy for the treatment of nasomaxillary hypoplasia: a case report.
AB  - Nasomaxillary hypoplasia clinically presents as a class lll deformity with
      hypoplasia or retrusion of the nasal bones and maxilla, which manifests as
      deficient projection of the nose.Lefort 2 osteotomy though introduced in 1950s,
      did not get its due attention till Henderson and Jackson published their landmark
      article, for the correction of Nasomaxillary hypoplasia in 1973. Accomplished
      surgeons can achieve a lot more in this rarely performed surgery when used in
      appropriate cases.

PMID- 23139554
TI  - Lipomas of oral cavity: case reports with review of literature.
AB  - Lipomas represent about 1 to 5% of all neoplasms of the oral cavity. Although
      relatively common, few large series of intraoral lipomas and its variants are
      seen in the literature. Therefore, the author presents the four cases of intra
      oral lipoma with one case of histological variant of lipoma, the fibrolipoma. All
      lesions were removed surgically with the intra-oral approach and none showed
      recurrence.

PMID- 23139556
TI  - Setting standards: A personal, national and international imperative.

PMID- 23139555
TI  - Oral myiasis: a rare entity.
AB  - Myiasis is the invasion of tissues and organs of human beings or other
      vertebrates by fly larvae. This phenomenon is well documented in the skin,
      especially among animals and people in tropical and subtropical areas.When
      tissues of the oral cavity are invaded by the parasitic larvae of flies, this
      condition is called oral myiasis. Oral myiasis is a rare condition that can be
      caused by several species of dipteran fly larvae and may be secondary to serious
      medical conditions. We hereby report a rare case of oral myiasis involving the
      palate in a 58-year-old diabetic patient and discuss the management of the same.

PMID- 23139557
TI  - Editorial.

PMID- 23139558
TI  - A comparative study between transbuccal and extra-oral approaches in treatment of
      mandibular fractures.
AB  - BACKGROUND AND OBJECTIVES: Mandibular angle fractures continue to be a common
      type of facial injury. The objectives in treatment are to effect rapid healing by
      anatomic reduction and fixation and to restore function and appearance with
      minimal disability and complications. Traditionally, when open techniques are
      utilised, the extra-oral approach is performed through a skin incision concealed
      in the submandibular crease. However, patients develop unsightly scars and there
      is a risk of injury to the marginal mandibular nerve. In comparison, the trans
      oral approach, performed through an oral mucosal incision, results in minimal
      external scarring or injury to the marginal mandibular nerve and allows direct
      visualisation and confirmation of the desired occlusion during the placement of
      the miniplates. The basic aim of the study was to provide a treatment for the
      mandibular fractures which results in minimal scarring and fulfills all the
      functional needs of the patient. STUDY DESIGN: Patients coming to KLES PK
      Hospital and MRC with mandibular angle fractures requiring open reduction and
      internal fixation admitted under OMFS were taken for the study. The sample size
      of the study was 15. In one group, the patients were treated by extra-oral
      approach and the other group by transbuccal approach. In patients treated by
      transbuccal approach, special armamentarium consisting of trocar, cannula, and
      cheek retractor were used; and in both the groups, semirigid fixation was done
      using two miniplates with around a distance of 1cm. RESULTS: Total of 15 patients
      were treated, 10 with transbuccal approach and 5 with submandibular approach. It
      has been found that both techniques fulfill the functional requirements of the
      patients. Patients treated with submandibular approach developed obvious
      unsightly scars, whereas transbuccal approach results in minimal scarring.
      CONCLUSION: The results associated with clinical observations suggest that
      transbuccal approach is a superior and less time consuming approach than
      extraoral approach, but it requires special instruments, lots of skill by the
      operating surgeon in using the armamentarium, and a skilled assistant.

PMID- 23139559
TI  - Evaluation of different treatment modalities for closure of oro-antral
      communications and formulation of a rational approach.
AB  - Oro-antral communication is a common occurrence following removal of maxillary
      premolars and molars because of anatomic proximity of root apices of these teeth
      and maxillary antrum. Various methods have been described in literature for
      closure of these communications which vary from simple local methods like buccal
      advancement flap to complex distal flaps and grafts. Out of these plethora of the
      treatment modalities available for the treatment of oro antral fistula, the most
      simple and commonly used ones are either the buccal flap or the buccal pad of
      fat. In our study we compared the results, advantages and disadvantages of using
      buccal advancement technique and buccal fat pad individually and also in
      combination. With this paper, we aim to shed light on the efficacy of buccal pad
      of fat and the buccal flap, either alone or together, for the closure of OAF of
      various regions. We also aim to provide a systematic and rational approach for
      repair of oro-antral communications.

PMID- 23139561
TI  - Bilateral inferiorly based nasolabial flaps for the management of advanced oral
      submucous fibrosis.
AB  - OBJECTIVES: To study the usefulness of bilateral inferiorly based nasolabial flap
      in the management of advanced oral submucous fibrosis in patients with
      interincisal opening (IIO) 15mm. To measure the Interincisal Opening (IIO),
      preoperatively, intra-operatively and at regular intervals during the follow-up
      period. To assess the vascularity and viability of the flap on the 1st, 7th and
      21st postoperative days. METHODS: 6 medically fit patients with a chief complaint
      of restricted mouth opening and interincisal opening less than 15 mm were chosen
      for the study. All the cases were diagnosed as advanced oral submucous fibrosis
      based on longstanding positive history of habits (chewing tobacco, betel nut
      etc.), clinical examination and histopathological examination. Intra-oral
      incisions were taken on the buccal mucosa for release of bands. All third molars
      were extracted. Bilateral intra-oral coronoidectomy was done if IIO less than 35
      mm was achieved intraoperatively. Bilateral nasolabial flaps were raised in the
      supramuscular plane and transferred intra-orally through a transbuccal tunnel.
      Periodic evaluation of the interincisal opening and pin prick test of the flap
      (to assess vascularity) was carried out. RESULTS: There was no incidence of
      infection in the transferred flap and the recipient site in all cases.
      Complications due to vascularity (blue flap or white flap) were not encountered.
      In our series of nasolabial flaps, flap loss either complete or partial was not
      encountered. Other complications like flap necrosis, damage to parotid duct,
      ectropion were not observed. After release of fibrotic bands a mean forced
      intraoperative mouth opening of 41.7 mm was achieved. On the first postoperative
      day a mean unforced mouth opening of 21.7 mm was achieved. Mean mouth opening of
      39.6 mm was achieved at 6 months, with a mean increase of 26.8 mm. Two of our
      cases required coronoidectomy since the intraoperative mouth opening achieved was
      less than 35mm. CONCLUSION: The nasolabial flap is a versatile flap, which can be
      successfully used in the reconstruction of defects created after the release of
      fibrotic bands. This flap is a good solution for the functional problems but the
      inevitable scar created becomes a drawback and may require a revision. All the
      cases treated for oral submucous fibrosis using bilateral nasolabial flaps showed
      adequate mouth opening at 6 months postoperatively, recommending its use.

PMID- 23139560
TI  - Surgical excision of intra-oral dermoid cyst under local anaesthesia: a review of
      nine cases.
AB  - OBJECTIVE: The purpose of this article is to highlight the effectiveness of local
      anaesthesia in the surgical excision of intral-oral dermoid cyst in the absence
      of available modern and efficient general anaesthetic options as experienced in
      our environment. PATIENTS AND METHODS: A retrospective review of nine patients
      with intra-oral dermoid cysts seen at the oral and maxillofacial surgery units of
      three specialist hospitals in eastern Nigeria was carried out between 1996 and
      2007. We used simple clinical findings and the aspiration technique for our
      provisional diagnosis and treated our patients by using local anaesthesia, which
      contains 2% lignocaine hydrochloride in 1: 80,000 adrenaline. RESULTS: Out of the
      nine cases seen, the male-to-female ratio was 2:1, representing six male and
      three female. The age range was 13-22 years, with a mean age of 19 years. The use
      of local anaesthesia was uneventful and despite the limited options of treatment
      and the absence of advanced imaging techniques we achieved total success and good
      results in all nine patients. CONCLUSION: The anaesthetic difficulties and
      uncertainties associated with the management of intral-oral dermoid cysts
      especially in an environment that lack modern general anaesthetic options can be
      avoided by the use of local anaesthesia. This may, therefore, be an effective
      alternative to difficult and sometime expensive general anaesthetic methods used
      in developed countries and could be emulated by oral and maxillofacial surgeons
      in poorer countries.

PMID- 23139562
TI  - Intrusion of anterior teeth to improve smile esthetics.
AB  - A gummy smile is probably one of the most common causes of an unaesthetic smile.
      Causes include overeruption of maxillary anterior teeth and maxillary vertical
      excess. Intrusion of maxillary anterior teeth with Orthodontics and Le forte I
      superior repositioning may form a part of the solution. Of late the use of micro
      implants have improved the smile esthetics of borderline surgical cases by
      allowing the Orthodontist to intrude teeth more than what was possible with
      conventional Orthodontics.

PMID- 23139563
TI  - Classifying odontogenic keratocysts as benign cystic neoplasms: a molecular
      insight into its aggressiveness.
AB  - OBJECTIVE: The present study was conducted with the aim to evaluate the
      expression of p53 in Odontogenic Keratocyst (OKC) and Ameloblastoma to correlate
      with the aggressiveness of these lesions. MATERIAL AND METHODS:
      Immunohistochemical (IHC) staining was performed using anti-p53 antibody in
      eighteen cases each of OKC and ameloblastoma. RESULTS: p53 positivity was seen in
      all the cases of OKCs and ameloblastomas. p53 positive cells were seen
      predominantly in the suprabasal cell layer of OKC and in the peripheral pre
      ameloblast like cells in ameloblastoma. Total p53 count was significantly higher
      in ameloblastoma as compared to OKC. But the intensely stained p53 cell count
      showed no statistically significant difference between the two lesions.
      CONCLUSION: The high p53 expression in OKC when compared with ameloblastoma,
      acknowledges OKC as an aggressive lesion and hence a more aggressive treatment
      modality is recommended.

PMID- 23139564
TI  - A retrospective study of 256 patients with space infection.
AB  - AIM: The purpose of this study was to retrospectively evaluate a series of
      patients with space infection. PATIENTS AND METHODS: In this study 256 patients
      with space infection over a period of two years were treated with intravenous
      antibiotic and prompt incision and drainage followed by culture and sensitivity
      tests in some cases. Data collection included demographic, anatomic treatment and
      complication information. RESULTS: The sample consisted of 256 patients with a
      mean age of 28 years. 7 patients were immunocompromised and 20 female patients
      were pregnant out of 84 female patients who were included in the study. Caries
      followed by implant failure were identified to be the most frequent cause for
      space infection. Trismus and dysphagia were present in over 70% of the cases. The
      vestibular masticator, perimandibular (submandibular, submental and/or
      sublingual) and parapharyngeal, submaxillary spaces were involved. Abscess was
      found in 76% of the cases. All the patients were drained under local anesthesia
      or conscious sedation except one patient who was drained under GA. Three deaths
      occurred. CONCLUSION: This study indicated that prompt incision and drainage
      along with intravenous antibiotic under local anesthesia or conscious sedation
      was the mainstay of treatment of severe space infection. Patients were relieved
      of their signs and symptoms by third day, however trismus may persist for 5-7
      days.

PMID- 23139565
TI  - Bifid mandibular condyle: a study of the clinical features, patterns and
      morphological variations using CT scans.
AB  - Bifid Mandibular Condyle (BMC) are usually diagnosed on routine radiographic
      examination, is described in the literature as a rare entity. It is reported that
      BMC has no predilection by sex or ethnic background or the age. The
      etiopathogenesis of BMC still remains controversial and proper description of the
      condition is not defined owing to fewer reported cases. Dental professionals
      should have some knowledge of this anatomic abnormality, as well as its
      implications for function and appropriate treatment modalities, so that they can
      be alert to this potential diagnosis. This paper reports the largest series of
      BMC, using CT scans with history of trauma and presents some of the
      characteristic clinical features.

PMID- 23139566
TI  - Cervical lymph node metastasis in oral squamous carcinoma preoperative assessment
      and histopathology after neck dissection.
AB  - BACKGROUND: The presence or absence of nodal metastasis has a great impact on the
      prognosis and survival of patients with head and neck cancer. The risk of occult
      metastasis is related to the method by which the lymph nodes are evaluated. It is
      possible to reduce the risk of undiagnosed metastasis with accurate imaging
      techniques and thus probably reduce the number of elective neck treatments. AIMS
      AND OBJECTIVES: To assess the accuracy of clinical palpation, CT Scan, Ultrasound
      and Ultrasound guided FNAC in prediction of lymph node metastasis in oral
      squamous cell carcinoma so that a suitable surgical neck dissection can be
      carried out. METHODS: Ten patients with oral squamous cell carcinoma who
      underwent 10 neck dissections (4 RND, 6 SOND) were included. All the patients
      underwent examination of neck pre operatively by palpation, Computed Tomography
      with contrast, Ultrasound and Ultrasound guided FNAC for no detection. The
      findings were correlated with the results of histopathologic examination of the
      neck specimen. The results were obtained after statistical analysis. RESULTS: Six
      neck dissection specimens showed metastatic lymph node involvement in
      postoperative histopathology. Lymph node involvement was identified
      preoperatively by palpation in 7 necks, CT in 3 necks, US in 9 necks and USFNAC
      was positive in 4 cases. The palpation showed 83% sensitivity, 50% specificity.
      CT showed sensitivity of 50%, specificity of 100%, US showed sensitivity of 100%,
      specificity of 25% and US-FNAC showed sensitivity of 67%, specificity of 100%.
      CONCLUSION: The palpation, CT Scan and US are equally accurate but the USFNAC is
      the most accurate technique in assessing metastasis in lymph nodes in patients
      with oral squamous cell carcinoma.

PMID- 23139568
TI  - Necrotizing cervical fasciitis: a case report and review of literature.
AB  - Necrotizing cervical fasciitis is a rare, fulminating infection causing extensive
      necrosis of the subcutaneous tissue and fascial planes with resultant skin
      gangrene. To reduce the morbitity and mortality from this condition, it requires
      early recognition and aggressive surgical debridment with appropriate antibiotic
      therapy. The origin is generally odontogenic and presents more often in
      immunocompromised patients. This article presents a case with typical clinical
      features and appropriate management of this condition. An review of literature
      was carried out for microbiology, pathogenesis, clinical features, diagnosis,
      management and prognosis of this condition.

PMID- 23139567
TI  - Mandibular invasion of squamous cell carcinoma: factors determining surgical
      resection of mandible using computerized tomography and histopathologic study.
AB  - AIM: Carcinoma of the mandibular region can be considered as an important,
      distinct entity associated with special problems relating to diagnosis,
      evaluation of extension, planning of treatment, surgical techniques, treatment
      result and prognosis. The study was aimed to assess the accuracy of computerized
      tomography in demonstrating mandibular invasion, to assess the role of anatomic
      structures like cancellous spaces, the inferior alveolar nerve and periodontal
      spaces in spread of carcinomas in the mandible and to determine the spread of
      tumour within the mandible and the resection procedure to be carried. MATERIALS
      AND METHODS: 11 mandibular specimens which were resected for squamous cell
      carcinoma were examined clinically, radiographically and histopathologically.
      Computerized tomography 120 KV, 40 to 130ma, obtaining slices starting from the
      center of lesion to the clearance, of the bone involvement distally and proximal
      to the lesion with excellent soft tissue or cortical bone interface with bone
      enhancement mode was used as a principle investigating tool to assess the tumour
      penetration in the mandible which was confirmed by histopathologic sections.
      RESULTS: A conditional probability test was conducted according to Bayes'
      theorem, and the results showed sensitivity 60% and specificity 77.8%, a false
      negative rate 40% and false positive rate 22.2%. A positive predictive value 69%
      and negative predicative value 70%. CONCLUSION: In our study the factors to be
      taken into consideration in deciding the type of resection are the pattern of
      tumour infiltration, irradiated or non irradiated mandibles, presence or absence
      of dentition, the inferior alveolar nerve involvement and the periodontal space
      involvement. The computerized tomography has a significant role in detecting the
      involvement of tumour in the mandible with enhanced settings.

PMID- 23139569
TI  - Correction of midface deficiency using intra-oral distraction device.
AB  - A wide variety of disease processes produce alteration of midfacial skeletal
      growth, resulting in moderate-to-severe midface deficiency presenting as
      retrusion associated with Angle's class III malocclusion. Most cases of midface
      deficiency are seen in patients of cleft lip/palate. The surgical procedure to
      correct the clefts, undertaken over a long period of time from infancy to the
      teens tends to take its toll on the soft tissues over the midface. The scarring
      that is a feature in these conditions results in hampering of normal growth of
      the midface causing the deformity. Conventional procedures to correct the
      deformity by surgical advancement have been less than satisfactory in terms of
      success. This is where the concept of multidimensional growth using distraction
      proved useful. Today distraction has proved to be a versatile tool in the
      correction of midface deficiencies due to its various advantages. Six patients of
      cleft lip/palate were taken up for advancement of the hypoplastic midface using
      intra-oral distractors with successful and stable results.

PMID- 23139570
TI  - Cleft lip: our experience in repair.
AB  - The ideally repaired cleft lip should provide a symmetrical cupid's bow, philtrum
      and a minimal scar. The lip length, pout and symmetry of the alar base should be
      maintained to achieve the best result. The most popular method for cleft lip
      repair is rotation advancement technique introduced by Millard which improves the
      relationship of alar base of cleft side, produces harmonious symmetry of the
      nostril, the surgical scar is masked in the philtral crest and nostril floor. In
      addition, it uses and preserves the lip anatomy, returns lip tissue into its
      normal position, minimizes amount of tissue discard and reconstructs orbicularis
      oris muscle. METHODOLOGY: We have assessed the incidence of cleft lip
      deformities, discussed the feasibility of repair by Millard, its modifications
      and evaluated the results of cleft lip repairs at our center. The study included
      158 patients of cleft lip and palate, of which 60 cleft lip patients underwent
      surgical repair. RESULT: The outcome of our surgical result was good and
      suggested quantitative changes with progressive diminution of asymmetry of the
      cleft and non cleft sides.

PMID- 23139571
TI  - Submental intubation: our experience.
AB  - INTRODUCTION: Airway management for patients who suffered midfacial fractures is
      complicated. In maxillofacial injuries, a choice has often to be made between
      different ways of intubation when surgical access to both the nasal and oral
      cavities is necessary. Submental intubation technique is an alternative to
      nasoendotracheal intubation and tracheostomy in the management of patients with
      severe midfacial fractures. This procedure is simple to do and has a low
      morbidity. MATERIAL: Submental intubation-paramedian technique has been used in
      15 cases from May 2005-April 2007 in Hosmat Hospital, Bangalore. All patients had
      fractures disturbing the dental occlusion plus either an associated fracture of
      the skull base or a displaced nasal fracture. RESULTS: Average duration of
      procedure was 7 minutes. Average duration of tube in vitro after surgery was 20
      hours. There were 2 postoperative complications of tube obstruction which were
      successfully managed. CONCLUSION: Submental intubation demands certain technical
      skills but it is simple, rapid and may avoid tracheostomy in selected patients.

PMID- 23139572
TI  - Malignant peripheral nerve cell tumour.
AB  - Malignant Peripheral Nerve Sheath Tumour (MPNST) also termed as spindle cell
      malignancy of the peripheral nerve schwann cell or neurogenic sarcoma represents
      10% of all soft tissue sarcomas. The tumour is usually found in lower extremities
      and only 10% to 20% of all lesions occur in head and neck region thus making it a
      rare entity. Central involvement, particularly in the jaw bones is quite unusual.
      Neurofibroma is one of the common nerve sheath tumours occurring in the soft
      tissues and generally appears in neurofibromatosis I (NF-I or von
      recklinghausen's disease). MPNST are uncommon sarcomas that almost always arise
      in the soft tissues. Here we report a case of intraosseous peripheral nerve
      sheath tumour occurring in the mandible and discuss the surgical management with
      adjuvant and neoadjuvant treatment plan.

PMID- 23139573
TI  - Glandular odontogenic cyst involving the posterior part of maxillary sinus, a
      rare entity.
AB  - The Glandular Odontogenic Cyst (GOC) was first coined by Gardner et al. [2], in
      1988 as an odontogenic origin, is a rare developmental lesion considered a
      distinct entity because of its uncommon clinical and histopathological
      characteristics. This lesion can involve either jaws, but the anterior region of
      the mandible is the most affected area. It strikes distinct age groups, with an
      average patient age of 50 years. Radiographically, GOC does not display specific
      or pathognomonic features. It may present as a multilocular or unilocular
      radiolucencies. The cyst has an aggressive nature and high tendency of
      recurrence, so long-term follow-up should be carried out. The treatment is
      controversial, varying from conservative methods to block excision. It is
      believed that the low prevalence of GOC in the literature is because of not only
      its rarity, but principally to the fact that its main characteristics are also
      found in other pathological entities, thereby generating controversial diagnoses.
      The aim of this paper is to present a rare case of Glandular Odontogenic Cyst
      (GOC), which is uncommon in the posterior maxilla, that mimicks the lateral
      odontogenic cyst/botroid odontogenic cyst/Central Muco-epidermoid carcinoma.
      Owing to its tendency to recur, the lesion needs careful and meticulous planning
      for its surgical removal.

PMID- 23139574
TI  - Pleomorphic adenoma of the soft palate.
AB  - Pleomorphic adenoma is the commonest benign salivary gland tumour, accounting for
      almost three fourths of all such tumours. Pleomorphic adenoma most commonly
      occurs in the parotid gland; however it is also encountered in the submandibular,
      sublingual and minor salivary glands.Almost half of all salivary gland tumours
      are malignant, pleomorphic adenoma is the commonest benign lesion.A case of
      pleomorphic adenoma arising denovo in the minor salivary glands is discussed.

PMID- 23139575
TI  - An unusual approach to retrieve right mandibular canine tooth, displaced into
      submandibular space following fracture mandible, using c-arm.
AB  - The purpose of this article is to present an unusual approach to retrieve a
      displaced tooth. In our patient the right mandibular canine was displaced into
      the right submandibular space during trauma. The displaced tooth was localized
      intraoperatively by the use of C-Arm radiography and retrieved surgically.

PMID- 23139576
TI  - Differential diagnosis of stafne idiopathic bone cyst with Digital Volume
      Tomography (DVT).
AB  - OBJECTIVES: The distinction between a pseudocyst and an intervention demanding
      cyst or process cannot always be found by 2D radiology. The differential
      diagnosis of a pseudocyst may become more difficult when adjacent processes are
      present. CASE: A symptom free 67-years-old man presented with a periapical
      radiolucency around the mandibular left second molar as well as at the impacted
      3rd molar. A comparison with an older panoramic x-ray showed no expansion during
      a 27 months period. The new panoramic x-ray and addtional Digital Volume
      Tomography (DVT) showed asymptomatic separate dental cyst at the impacted wisdom
      tooth and the missing lingual cortical border in the apical region of the 2nd
      lower molar. This finding along with clinical vitality of the 1st and 2nd left
      molars led to the conclusion that the presented pathology was a Stafne Idiopathic
      Bone Cyst (SIBC) which needed no surgical intervention. DISCUSSION: The
      additional use of DVT 3D examination may help in diagnosis of SIBC prior to
      surgical interventions thus avoiding unwanted surgical intervention.

PMID- 23139577
TI  - Nevoid-basal cell carcinoma syndrome: a case report and overview on diagnosis and
      management.
AB  - Nevoid Basal Cell Carcinoma Syndrome (NBCCS) is a rare condition characterized by
      varied clinical manifestations like multiple Basal Cell Carcinomas (BCC),
      multiple Keratocystic Odontogenic Tumours (KCOT), palmar and/or plantar pits and
      ectopic calcification of the falx cerebri, which are considered as the major
      criteria for diagnosis. The occurrence of jaw manifestations makes it an
      important diagnostic problem for oral and maxillofacial surgeons and often
      clinicians encounter this aspect which finally leads to the diagnosis of this
      syndrome. This paper reports a case of NBCCS and provides an overview on the
      diagnosis and management of this enigmatic entity.

PMID- 23139578
TI  - Juvenile trabecular ossifying fibroma of the mandible.
AB  - Juvenile Ossifying Fibroma (JOF) is a rare fibro-osseus neoplasm in young
      children. This lesion is locally aggressive and spreads quickly. It is usually
      asymptomatic, achieving a large size. Owing to its aggressive behavior and high
      recurrence rate, early detection and complete surgical excision are essential.
      This report details the diagnosis and treatment of a 3-year-old girl presenting
      with a mandibular swelling that was subsequently determined to be juvenile
      ossifying fibroma.

PMID- 23139579
TI  - Management of juvenile ossifying fibroma in the maxilla and mandible.
AB  - We present three cases with juvenile ossifying fibroma. Two occurring in the
      maxilla, and one in the mandible. All three cases presented with a major swelling
      in the face. After clinical and radiological evaluation the lesions were
      surgically excised and sent for histopathological evaluation. Two histological
      types of juvenile ossifying fibroma were found, the psammatous type in two cases
      and the trabecular pattern in one case. Although juvenile ossifying fibroma is an
      uncommon clinical entity, its aggressive local behaviour and high recurrence rate
      mean that it is important to make an early diagnosis. It is also important to
      apply the appropriate treatment and to follow-up the patient closely over the
      long term. This report describes the diagnosis and treatment of juvenile
      ossifying fibroma in the maxilla and the mandible. It also emphasizes the
      importance of considering the less aggressive options as a first line of
      treatment before choosing the aggressive approach when dealing with children.

PMID- 23139580
TI  - Juvenile ossifying fibroma of maxilla.
AB  - Juvenile ossifying fibroma is a benign, but potentially aggressive, fibroosseous
      tumour of the craniofacial bones. The authors describe a case of a juvenile
      ossifying fibroma of maxilla presenting in a 14-year-old girl and review the
      histology, clinical behavior, and management of this uncommon but disfiguring
      lesion.

PMID- 23139581
TI  - Atypical case of periapical adenomatoid odontogenic tumour.
AB  - The Adenomatoid Odontogenic Tumour (AOT) is a progressively growing asymptomatic
      benign non-invasive lesion. A rare subvariant of the extrafollicular type of AOT
      may mimic periapical disease radiographically. We report a 45-year-old male with
      a periapical radiolucent lesion affecting maxillary central incisor tooth.
      Initially suspicious of periapical pathology, although clinical findings seemed
      to indicate a nonendodontic cause. The lesion was surgically explored and
      histopathological examination revealed the presence of AOT. This particular
      subvariant is very rare indeed, as available literature only 8 cases have been
      reported.

PMID- 23139582
TI  - A radiolucent lesion crossing the midline in maxilla: a rare presentation of
      odontogenic keratocyst in young patient.
AB  - Odontogenic Keratocyst (OKC) is a developmental non-inflammatory odontogenic cyst
      which is proposed to be arising from cell rests of dental lamina. Among the jaw
      cysts OKCs account for third most common following radicular and dentigerous
      cyst. Most of the studies have stated that posterior part of the mandible is the
      most common site, but there are inconsistencies regarding the prominent location
      of OKCs in the maxilla. Very few studies and cases are reported with OKCs
      crossing maxillary midline. If do occur they are in older individuals. According
      to WHO reclassification, this cyst is considered as Keratocystic Odontogenic
      Tumour (KCOT) because of its neoplastic nature. This article describes a rare
      site of occurrence of this lesion especially in young patient.

PMID- 23139583
TI  - Unusual maxillofacial injury.

PMID- 23139584
TI  - Abducent nerve palsy following an inferior alveolar nerve block.

PMID- 23139585
TI  - Two rare causes of frey syndrome.

PMID- 23139586
TI  - Simultaneous resection and reconstruction of the nose using frontal flap.

PMID- 23139587
TI  - Molecular interaction analysis of cigarette smoke carcinogens NNK and NNAL with
      enzymes involved in DNA repair pathways: An in silico approach.
AB  - DNA damage occurs almost all the times in cells, but is repaired also
      continuously. Occurrence of all these mutations and their accumulation in one
      cell which finally becomes tumorigenic/carcinogenic appears possible if the DNA
      repair mechanism is hampered. We hypothesize that alterations in DNA repair
      pathways, either all or at least at one i.e. genetic, translational or
      posttranslational level, becomes quite imperative for the initiation and
      progression of Cancer. Therefore, we investigated the interaction capability of
      some carcinogens with the enzymes involved in the DNA repair mechanisms.
      Cigarette smoke's derivatives like NNK and NNAL are well established carcinogens.
      Hence, we analyzed 72 enzymes involved in the DNA repair Mechanisms for their
      interactions with ligands (NNK and NNAL). The binding efficiencies with enzymes
      ranging from +36.96 to -7.47 Kcal/Mol. Crystal Structure of Human Carbonmonoxy
      Haemoglobin at 1.25 A Resolution, PDB ID-1IRD as a +Ve control, showed binding
      energy -6.31 to -6.68 Kcal/Mol. and Human heat shock factor-binding protein 1,
      PDB ID- 3CI9 as a -Ve control, showed - 3.91 to +2.09 Kcal/Mol. Binding was
      characterized for the enzymes sharing equivalent or better interaction as
      compared to +Ve control. Study indicated the loss of functions of these enzymes,
      which probably could be a reason for fettering of DNA repair pathways resulting
      in damage accumulation and finally cancer formation.

PMID- 23139588
TI  - Distribution and characterization of simple sequence repeats in Gossypium
      raimondii genome.
AB  - Simple sequence repeats (SSRs) can be derived from the complete genome sequence.
      These markers are important for gene mapping as well as marker-assisted selection
      (MAS). To develop SSRs for cotton gene mapping, we selected the complete genome
      sequence of Gossypium raimondii, which consisted of 4447 non-redundant scaffolds.
      Out of 775.2 Mb sequence examined, a total of 136,345 microsatellites were
      identified with a density of 5.69 kb per SSR in the G. raimondii genome leading
      to development of 112,177 primer pairs. The distributions of SSRs in the genome
      were non-random. Among the different motifs ranging from 1 to 6 bp, penta
      nucleotide repeats were most abundant (30.5%), followed by tetra-nucleotide
      repeats (18.2%) and di-nucleotide repeats (16.9%). Among all identified 457 motif
      types, the most frequently occurring repeat motifs were poly-AT/TA, which
      accounted for 79.8% of the total di-nt SSRs, followed by AAAT/TTTA with 51.5% of
      the total tetra-nucleotede. Further, 18,834 microsatellites were detected from
      the protein-coding genes, and the frequency of gene containing SSRs was 46.0% in
      40,976 genes of G. raimondii. These genome-based SSRs developed in the present
      study will lay the groundwork for developing large numbers of SSR markers for
      genetic mapping, gene discovery, genetic diversity analysis, and MAS breeding in
      cotton.

PMID- 23139589
TI  - Homology Modeling and Functional Characterization of PR-1a Protein of Hordeum
      vulgare subsp. Vulgare.
AB  - Pathogenesis-related protein 1a of Hordeum vulgare subsp. Vulgare (HvPR-1a) is
      induced by various pathogens and stress related factors. It plays important roles
      in plant defense system. Since the discovery of HvPR-1a a great deal of research
      has been focused on its isolation and characterization. However, three
      dimensional structure of HvPR-1a is still unknown. 3D structure can be used for
      determining protein function, and identifying novel protein folds and potential
      targets for regulation. The protein model was developed using MODELLER 9v10.
      Physicochemical characterization and functional annotation of the model carried
      out with Expasy's ProtParam server and three different conserved domain finding
      programs including InterProScan, Proteins Families Database (Pfam), and NCBI
      Conserved Domains Database (NCBI-CDD). Applying validation programs revealed that
      the model has good quality and the RMSD value is 0.7. The predicted model
      submitted in Protein Model Database, PMDB for public use. This model will be used
      in wide range of studies for functional analysis and improvement activity of the
      protein.

PMID- 23139590
TI  - Insights from the docking analysis of biologically active compounds from plant
      Litsea Genus as potential COX-2 inhibitors.
AB  - Litsea spp of Laural family are traditionally used as herbal medicine for
      treating inflammation including gastroenterologia, oedema and rheumatic
      arthritis. Therefore, it is of interest to investigate and understand the
      molecular principles for such actions. Here, we have illustrated the binding of
      thirteen Litsea derived biologically active compounds against the inflammation
      associated target COX (cyclo-oxygenase) -2 enzymes. We compared the binding
      information of these compounds with a selected number of already known COX-2
      inhibitors. The comparison reflected that some of these compounds such as
      linderol, catechin, 6'-hydroxy-2',3',4' - trimethoxy-chalcone and litseaone have
      better or equivalent binding features compared to already known inhibitory
      compounds namely celecoxib, acetylsalicylic acid, rofecoxib. Therefore, all these
      small compounds reported from plant Litsea spp were found to possess potential
      medicinal values with anti-inflammatory properties.

PMID- 23139591
TI  - PCR-based molecular characterization, phylogenetic analysis and secondary
      structure of the 28S rDNA of Thaparocleidus wallagonius (Monogenea:
      Dactylogyridae) - the most primitive species of this genus from India.
AB  - Species of the monogenean genus Thaparocleidus are specific to freshwater
      siluriform fish. The infection caused by these gill parasites are a major health
      problem to fish. But, to focus the control strategies of these parasites, first
      it is important to establish an accurate discrimination by molecular methods. In
      the present study, phylogenetic and structural analysis of 28S region of
      ribosomal DNA of T. wallagonius species collected from fish Wallago attu from
      Meerut (U.P.), India, was carried out. In the first step, we amplified, sequenced
      28S region of ribosomal DNA of T. wallagonius to establish the phylogenetic
      relationship with other species of this genus. T. wallagonius found on gill
      filaments of fish W. attu, is the most primitive parasite of this genus from
      India, was unequivocally discriminate from other species of the same genus in
      this study. A secondary-structure model of the large subunit rDNA was also
      predicted using a combined comparative and thermodynamic approach. Molecular
      morphometric and phylogenetic relationship of T. wallagonius are discussed in
      detailed that based on molecular analysis using bioinformatic tools.

PMID- 23139592
TI  - Arginine and Lysine interactions with pi residues in metalloproteins.
AB  - Metalloproteins have many different functions in cells such as enzymes; signal
      transduction, transport and storage proteins. About one third of all proteins
      require metals to carry out their functions. In the present study we have
      analyzed the roles played by Arg and Lys (cationic side chains) interactions with
      pi (Phe, Tyr or Trp) residues and their role in the structural stability of
      metalloproteins. These interactions might play an important role in the global
      conformational stability in metalloproteins. In spite of its lower natural
      occurrence (1.76%) the number of Trp residues involved in energetically
      significant interactions is higher in metalloproteins.

PMID- 23139593
TI  - Molecular modeling and prediction of binding mode and relative binding affinity
      of Art-Qui-OH with P. falciparum Histo-Aspartic Protease (HAP).
AB  - The relative binding affinity in terms of DeltaDeltaG (bind-cald) value of the
      antimalarial compound artemisinin-quinine hybrid is primarily derived and is
      discussed in this article with reference to the DeltaG (bind-cald) values of two
      known inhibitors Pepstatin-A and KNI-10006 complexed with HAP enzyme. The DeltaG
      (bind-cald) value for KNI-10006 and Pepstatin-A is -14.10 kcal/mol and -13.09
      kcal/mol respectively. The MM-GB/SA scoring results in the relative binding
      energy (DeltaDeltaG (bind-cald)) of the hybrid molecule with respect to Pepstatin
      A as 2.43 kcal/mol and 3.44 kcal/mol against KNI-10006. The overall binding mode
      of Art-Qui-OH resembles that of Pepstatin-A binding in HAP active site. We
      suggest here that the DeltaDeltaG (bind-cald) value & proposed binding mode of
      the Art-Qui-OH for HAP enzyme should be considered for further structure-based
      drug design effort.

PMID- 23139594
TI  - Molecular docking and virtual screening for novel protein tyrosine phosphatase 1B
      (PTP1B) inhibitors.
AB  - Protein tyrosine phosphatase 1B (PTP1B) functions as major negative regulator of
      insulin and leptin signaling pathways. In view of this, PTP1B is an significant
      target for drug development against cancer, diabetes and obesity. The aim of the
      current study is to identify PTP1B inhibitors by means of virtual screening with
      docking. 523,366 molecules from ZINC database have been screened and based on
      DOCK grid scores and hydrogen bonding interactions five new potential inhibitors
      were identified. ZINC12502589, ZINC13213457, ZINC25721858, ZINC31392733 and
      ZINC04096400 were identified as potential lead molecules for inhibition of PTP1B.
      The identified molecules were subjected to Lipinski's rule of five parameters and
      found that they did not violate any rule. More specific analysis of
      pharmacological parameters may be scrutinized through a complete ADME/Tox
      evaluation. Pharma algorithm was used to Calculate ADME-Tox profiles for such
      molecules. In general, all the molecules presented advantages and as well as
      disadvantages when compared to each other. No marked difference in health effects
      and toxicity profiles were observed among these molecules.

PMID- 23139595
TI  - CIBMAN: Database exploring Citrus biodiversity of Manipur.
AB  - The rich wealth of Citrus genetic resources makes India to enjoy a remarkable
      position in the "Citrus belt of the world". We have developed CIBMAN, a unique
      database on Citrus biodiversity of Manipur which comprises 33 accessions
      collected through extensive survey for more than three years. CIBMAN provides
      integrated access to Citrus species through sophisticated web interface which has
      following capabilities a) morphological details, b) socio-economic details, c)
      taxonomic details and d) geographical distribution. Morphological variability
      among Citrus accessions is due to variance in their genome which contributes to
      diverse agronomical traits and diverse bioactive compounds of high value. This
      diverse gene pool can be potential source for genetic improvement of existing
      cultivars and rootstocks. Systematic collection, characterization and
      conservation of the underutilized or lesser exploited varieties is required for
      incorporating in breeding program and conserve the germplasm from ever going on
      genetic erosion. This database will be useful for scientific validations and
      updating of traditional wisdom in bioprospecting aspects especially
      industrialization of Citrus found in the state. Further, the features will be
      suited for detailed investigation on potential medicinal and edible Citrus that
      make CIBMAN a powerful tool for sustainable management. AVAILABILITY:
      http://ibsd.gov.in/cibman.

PMID- 23139596
TI  - MicroRNA Targets - How to predict?
AB  - A number of web tools are available for the prediction and identification of
      target microRNAs (miRNAs). The choice, availability, validity and selection of an
      optimal yet appropriate tool are a challenge for the design of high throughput
      assays with promising miRNA targets. The current trends and challenges for target
      microRNAs (miRNAs) prediction, identification and selection is described in this
      review.

PMID- 23139597
TI  - Reversible inactivation of dihydrolipoamide dehydrogenase by Angeli's salt.
AB  - Dihydrolipoamide dehydrogenase (DLDH) is a key component of 3 mitochondrial alpha
      keto acid dehydrogenase complexes including pyruvate dehydrogenase complex, alpha
      ketoglutarate dehydrogenase complex, and branched chain amino acid dehydrogenase
      complex. It is a pyridine-dependent disulfide oxidoreductase that is very
      sensitive to oxidative modifications by reactive nitrogen species (RNS) and
      reactive oxygen species (ROS). The objective of this study was to investigate the
      mechanisms of DLDH modification by RNS derived from Angeli's salt. Studies were
      conducted using isolated rat brain mitochondria that were incubated with varying
      concentrations of Angeli's salt followed by spectrophotometric enzyme assays,
      blue native gel analysis, and 2-dimensional gel-based proteomic approaches.
      Results show that DLDH could be inactivated by Angeli's salt in a concentration
      dependent manner and the inactivation was a targeting rather than a random
      process as peroxynitrite did not show any detectable inhibitory effect on the
      enzyme's activity under the same experimental conditions. Since Angeli's salt can
      readily decompose at physiological pH to yield nitroxyl anion (HNO) and nitric
      oxide, further studies were conducted to determine the actual RNS that was
      responsible for DLDH inactivation. Results indicate that it was HNO that exerted
      the effect of Angeli's salt on DLDH. Finally, two-dimensional Western blot
      analysis indicates that DLDH inactivation by Angeli's salt was accompanied by
      formation of protein s-nitrosothiols, suggesting that s-nitrosylation is likely
      the cause of loss in enzyme's activity. Taken together, the present study
      provides insights into mechanisms of DLDH inactivation induced by HNO derived
      from Angeli's salt.

PMID- 23139598
TI  - Steroid-sparing strategies in the management of ulcerative colitis: efficacy of
      leukocytapheresis.
AB  - Active ulcerative colitis (UC) is frequently associated with infiltration of a
      large number of leukocytes into the bowel mucosa. Leukocytapheresis is a novel
      nonpharmacologic approach for active UC, in which leukocytes are mechanically
      removed from the circulatory system. Current data indicate that leukocytapheresis
      is efficacious in improving response and remission rates with excellent
      tolerability and safety in patients with UC. Corticosteroid therapy remains a
      mainstay in the treatment of active UC; however, long-term, high doses of
      corticosteroids usually produce predictable and potentially serious side effects.
      If leukocytapheresis can spare patients from exposure to corticosteroids, the
      risk of steroid-induced adverse events should be minimized. This may be of great
      benefit to patients because severe side effects of steroids seriously impair
      health-related quality of life. In this article, we reviewed current evidence on
      whether leukocytapheresis can avoid or reduce the use of corticosteroids in the
      management of patients with UC. Several studies have shown that leukocytapheresis
      was effective for steroid-naive patients with active UC. Furthermore, both short
      term and long-term studies have demonstrated the steroid-sparing effects of
      leukocytapheresis therapy in patients with UC. Although the evidence level is not
      striking, the available data suggest that leukocytapheresis can avoid or reduce
      the use of corticosteroids in the management of UC. Large, well-designed clinical
      trials are necessary to more accurately evaluate the steroid-sparing effects of
      leukocytapheresis in the management of UC.

PMID- 23139599
TI  - Omega-3 fatty acids for the treatment of non-alcoholic fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) has been recognized as a major health
      burden. It is the most important cause of chronic liver disease and a major
      independent cardiovascular risk factor. Lacking a definite treatment for NAFLD, a
      specific diet and an increase in physical activity represent the most commonly
      used therapeutic approaches. In this review, major literature data about the use
      of omega-3 polyunsaturated fatty acids (n-3 PUFAs) as a potential treatment of
      NAFLD have been described. n-3 PUFAs, besides having a beneficial impact on most
      of the cardio-metabolic risk factors (hypertension, hyperlipidemia, endothelial
      dysfunction and atherosclerosis) by regulating gene transcription factors [i.e.,
      peroxisome proliferator-activated receptor (PPAR) alpha, PPARgamma, sterol
      regulatory element-binding protein-1, carbohydrate responsive element-binding
      protein], impacts both lipid metabolism and on insulin sensitivity. In addition
      to an enhancement of hepatic beta oxidation and a decrease of the endogenous
      lipid production, n-3 PUFAs are able to determine a significant reduction of the
      expression of pro-inflammatory molecules (tumor necrosis factor-alpha and
      interleukin-6) and of oxygen reactive species. Further strengthening the results
      of the in vitro studies, both animal models and human intervention trials, showed
      a beneficial effect of n-3 PUFAs on the severity of NAFLD as expressed by
      laboratory parameters and imaging measurements. Despite available results
      provided encouraging data about the efficacy of n-3 PUFAs as a treatment of NAFLD
      in humans, well-designed randomized controlled trials of adequate size and
      duration, with histological endpoints, are needed to assess the long-term safety
      and efficacy of PUFA, as well as other therapies, for the treatment of NAFLD and
      non-alcoholic steatohepatitis patients. It is worthwhile to consider that n-3
      PUFAs cannot be synthesized by the human body and must be derived from exogenous
      sources (fish oil, flaxseeds, olive oil) which are typical foods of the
      Mediterranean diet, known for its beneficial effects in preventing obesity,
      diabetes and, in turn, cardiovascular events. According to these data, it is
      important to consider that most of the beneficial effects of n-3 PUFAs can also
      be obtained by an equilibrate nutrition program.

PMID- 23139600
TI  - Changes of the cytokine profile in inflammatory bowel diseases.
AB  - Cytokines are indispensable signals of the mucosa-associated immune system for
      maintaining normal gut homeostasis. An imbalance of their profile in favour of
      inflammation initiation may lead to disease states, such as that is observed in
      inflammatory bowel diseases (IBD). Although Crohn's disease (CD) is often
      described as a prototype of T-helper 1-type diseases, and ulcerative colitis (UC)
      is traditionally viewed as a T-helper 2-mediated condition, the classic paradigm,
      which categorises cytokines into pro- and anti-inflammatory groups, has recently
      been changed. The inflammation regulatory pathways may not be mutually exclusive
      as individual cytokines can have diverse and even opposing functions in various
      clinical and immunological settings. None the less there are many common
      immunological responses in IBD that are mediated by cytokines. Although they
      regulate and influence the development, course and recurrence of the inflammatory
      process, the concrete pathogenic role of these small signaling molecules is
      sometimes not unambiguous in the subtypes of the disease. Our aim is to review
      the current information about pro- and anti-inflammatory effects of traditionally
      studied and recently discovered cytokines in the pathogenesis of UC and CD. The
      better understanding of their production and functional activity may lead to the
      development of new therapeutic modalities.

PMID- 23139602
TI  - Effectiveness of impedance monitoring during radiofrequency ablation for
      predicting popping.
AB  - AIM: To retrospectively evaluate the effectiveness of impedance monitoring for
      predicting popping during radiofrequency ablation (RFA) using internally cooled
      electrodes. METHODS: We reviewed 140 patients (94 males, 46 females; age range
      73.0 +/- 11.1 year) who underwent RFA between February 2006 and November 2008
      with a modified protocol using a limited power delivery rather than a
      conventional one to avoid popping. All the patients provided their written
      informed consent, and the study was approved by the institutional review board.
      Intraprocedural impedances were measured for the study subjects, and the tumors
      were classified into three types according to the characteristics of their
      impedance curves: increasing, flat, or decreasing. The tumors were further sorted
      into seven subtypes (A-G) depending on the curvature of the impedance curve's
      increase or decrease. Relative popping rates were determined for the three types
      and seven subtypes. A chi-square test was performed to estimate statistical
      significance. RESULTS: A total of 148 nodules treated by RFA were analyzed. The
      study samples included 132 nodules of hepatocellular carcinoma, 14 nodules of
      metastatic liver cancer, and two nodules of intrahepatic cholangiocarcinoma. The
      numbers of nodules with each impedance curve type were as follows: 37 increasing
      type nodules, 43 flat-type nodules, and 68 decreasing-type nodules. Popping
      occurrence rates were 24.3%, 46.5% and 64.7%, respectively. Flat-type nodules
      exhibited a significantly higher rate of popping compared to increasing-type
      nodules (P = 0.039). Decreasing-type nodules exhibited a significantly higher
      rate of popping compared to increasing-type nodules (P < 0.0001). Notably,
      nodules that showed a sharp decrease in impedance in the latter ablation period
      (subtype E) exhibited a significantly higher rate of popping compared to other
      subtypes. CONCLUSION: Intraprocedural impedance monitoring can be a useful tool
      to predict the occurrence of popping during liver tumor RFA performed with
      internally cooled electrodes.

PMID- 23139601
TI  - Crohn's and colitis in children and adolescents.
AB  - Crohn's disease and ulcerative colitis can be grouped as the inflammatory bowel
      diseases (IBD). These conditions have become increasingly common in recent years,
      including in children and young people. Although much is known about aspects of
      the pathogenesis of these diseases, the precise aetiology is not yet understood,
      and there remains no cure. Recent data has illustrated the importance of a number
      of genes-several of these are important in the onset of IBD in early life,
      including in infancy. Pain, diarrhoea and weight loss are typical symptoms of
      paediatric Crohn's disease whereas bloody diarrhoea is more typical of colitis in
      children. However, atypical symptoms may occur in both conditions: these include
      isolated impairment of linear growth or presentation with extra-intestinal
      manifestations such as erythema nodosum. Growth and nutrition are commonly
      compromised at diagnosis in both Crohn's disease and colitis. Consideration of
      possible IBD and completion of appropriate investigations are essential to ensure
      prompt diagnosis, thereby avoiding the consequences of diagnostic delay. Patterns
      of disease including location and progression of IBD in childhood differ
      substantially from adult-onset disease. Various treatment options are available
      for children and adolescents with IBD. Exclusive enteral nutrition plays a
      central role in the induction of remission of active Crohn's disease. Medical and
      surgical therapies need to considered within the context of a growing and
      developing child. The overall management of these chronic conditions in children
      should include multi-disciplinary expertise, with focus upon maintaining control
      of gut inflammation, optimising nutrition, growth and quality of life, whilst
      preventing disease or treatment-related complications.

PMID- 23139603
TI  - Several factors including ITPA polymorphism influence ribavirin-induced anemia in
      chronic hepatitis C.
AB  - AIM: To construct formulae for predicting the likelihood of ribavirin-induced
      anemia in pegylated interferon alpha plus ribavirin for chronic hepatitis C.
      METHODS: Five hundred and sixty-one Japanese patients with hepatitis C virus
      genotype 1b who had received combination treatment were enrolled and assigned
      randomly to the derivation and confirmatory groups. Single nucleotide
      polymorphisms at or nearby ITPA were genotyped by real-time detection polymerase
      chain reaction. Factors influencing significant anemia (hemoglobin concentration
      < 10.0 g/dL at week 4 of treatment) and significant hemoglobin decline (declining
      concentrations > 3.0 g/dL at week 4) were analyzed using multiple regression
      analyses. Prediction formulae were constructed by significantly independent
      factors. RESULTS: Multivariate analysis for the derivation group identified four
      independent factors associated with significant hemoglobin decline: hemoglobin
      decline at week 2 [P = 3.29 * 10(-17), odds ratio (OR) = 7.54 (g/dL)], estimated
      glomerular filtration rate [P = 2.16 * 10(-4), OR = 0.962 (mL/min/1.73 m(2))],
      rs1127354 (P = 5.75 * 10(-4), OR = 10.94) and baseline hemoglobin [P = 7.86 * 10(
      4), OR = 1.50 (g/dL)]. Using the model constructed by these factors, positive and
      negative predictive values and predictive accuracy were 79.8%, 88.8% and 86.2%,
      respectively. For the confirmatory group, they were 83.3%, 91.0% and 88.3%. These
      factors were closely correlated with significant anemia. However, the model could
      not be constructed, because no patients with rs1127354 minor genotype CA/AA had
      significant anemia. CONCLUSION: Reliable formulae for predicting the likelihood
      of ribavirin-induced anemia were constructed. Such modeling may be useful in
      developing individual tailoring and optimization of ribavirin dosage.

PMID- 23139604
TI  - Characteristics of deslanoside-induced modulation on jejunal contractility.
AB  - AIM: To characterize the dual effects of deslanoside on the contractility of
      jejunal smooth muscle. METHODS: Eight pairs of different low and high contractile
      states of isolated jejunal smooth muscle fragment (JSMF) were established.
      Contractile amplitude of JSMF in different low and high contractile states was
      selected to determine the effects of deslanoside, and Western blotting analysis
      was performed to measure the effects of deslanoside on myosin phosphorylation of
      jejunal smooth muscle. RESULTS: Stimulatory effects on the contractility of JSMF
      were induced (45.3% +/- 4.0% vs 87.0% +/- 7.8%, P < 0.01) by deslanoside in 8 low
      contractile states, and inhibitory effects were induced (180.6% +/- 17.8% vs
      109.9% +/- 10.8%, P < 0.01) on the contractility of JSMF in 8 high contractile
      states. The effect of deslanoside on the phosphorylation of myosin light chain of
      JSMF in low (78.1% +/- 4.1% vs 96.0% +/- 8.1%, P < 0.01) and high contractile
      state (139.2% +/- 8.5% vs 105.5 +/- 7.34, P < 0.01) was also bidirectional.
      Bidirectional regulation (BR) was abolished in the presence of tetrodotoxin.
      Deslanoside did not affect jejunal contractility pretreated with the Ca(2+)
      channel blocker verapamil or in a Ca(2+)-free assay condition. The stimulatory
      effect of deslanoside on JSMF in a low contractile state (low Ca(2+) induced) was
      abolished by atropine. The inhibitory effect of deslanoside on jejunal
      contractility in a high contractile state (high Ca(2+) induced) was blocked by
      phentolamine, propranolol and L-NG-nitro-arginine, respectively. CONCLUSION:
      Deslanoside-induced BR is Ca(2+) dependent and is related to cholinergic and
      adrenergic systems when JSMF is in low or high contractile states.

PMID- 23139606
TI  - Comparative effectiveness of i-SCANTM and high-definition white light
      characterizing small colonic polyps.
AB  - AIM: To evaluate accuracy of in vivo diagnosis of adenomatous vs non-adenomatous
      polyps using i-SCAN digital chromoendoscopy compared with high-definition white
      light. METHODS: This is a single-center comparative effectiveness pilot study.
      Polyps (n = 103) from 75 average-risk adult outpatients undergoing screening or
      surveillance colonoscopy between December 1, 2010 and April 1, 2011 were
      evaluated by two participating endoscopists in an academic outpatient endoscopy
      center. Polyps were evaluated both with high-definition white light and with i
      SCAN to make an in vivo prediction of adenomatous vs non-adenomatous pathology.
      We determined diagnostic characteristics of i-SCAN and high-definition white
      light, including sensitivity, specificity, and accuracy, with regards to
      identifying adenomatous vs non-adenomatous polyps. Histopathologic diagnosis was
      the gold standard comparison. RESULTS: One hundred and three small polyps,
      detected from forty-three patients, were included in the analysis. The average
      size of the polyps evaluated in the analysis was 3.7 mm (SD 1.3 mm, range 2 mm to
      8 mm). Formal histopathology revealed that 54/103 (52.4%) were adenomas, 26/103
      (25.2%) were hyperplastic, and 23/103 (22.3%) were other diagnoses include
      "lymphoid aggregates", "non-specific colitis," and "no pathologic diagnosis."
      Overall, the combined accuracy of endoscopists for predicting adenomas was
      identical between i-SCAN (71.8%, 95%CI: 62.1%-80.3%) and high-definition white
      light (71.8%, 95%CI: 62.1%-80.3%). However, the accuracy of each endoscopist
      differed substantially, where endoscopist A demonstrated 63.0% overall accuracy
      (95%CI: 50.9%-74.0%) as compared with endoscopist B demonstrating 93.3% overall
      accuracy (95%CI: 77.9%-99.2%), irrespective of imaging modality. Neither
      endoscopist demonstrated a significant learning effect with i-SCAN during the
      study. Though endoscopist A increased accuracy using i-SCAN from 59% (95%CI:
      42.1%-74.4%) in the first half to 67.6% (95%CI: 49.5%-82.6%) in the second half,
      and endoscopist B decreased accuracy using i-SCAN from 100% (95%CI: 80.5%-100.0%)
      in the first half to 84.6% (95%CI: 54.6%-98.1%) in the second half, neither of
      these differences were statistically significant. CONCLUSION: i-SCAN and high
      definition white light had similar efficacy predicting polyp histology.
      Endoscopist training likely plays a critical role in diagnostic test
      characteristics and deserves further study.

PMID- 23139605
TI  - Expression characteristics and diagnostic value of annexin A2 in hepatocellular
      carcinoma.
AB  - AIM: To investigate the characteristics and diagnostic value of annexin A2
      (ANXA2) expression in cancerous tissues and sera of patients with hepatitis B
      virus (HBV)-related hepatocellular carcinoma (HCC). METHODS: Levels of liver
      ANXA2 gene transcription or protein expression were analyzed in HCC-, their self
      controlled precancerous-, and distant cancerous- tissues from 30 HCC. Serum
      levels of ANXA2 expression in 115 patients with HCC, 25 with metastatic liver
      cancer, 35 with chronic hepatitis, 28 with acute hepatitis, 38 with cirrhosis,
      and 30 healthy controls were determined. Clinicopathological characteristics of
      circulating ANXA2 expression were analyzed, and its diagnostic efficiency and
      clinical values in HCC were evaluated. RESULTS: ANXA2 expression was localized in
      both cell membrane and cytoplasm in HCC tissue, mainly in the cytoplasm of
      matched adjacent cancerous tissue, and there was almost no positive staining in
      matched distant cancerous tissue. Abnormal expression of liver ANXA2 was present
      in HCC tissues compared with self-controlled adjacent- and distant-cancerous
      tissues at protein or mRNA level. Circulating ANXA2 in HCC patients was
      significantly higher than that of other liver diseases (P < 0.01) except
      metastatic liver cancer. If the diagnostic cutoff value of ANXA2 level was more
      than 18 ng/mL, the incidence of serum ANXA2 was 86.96% in the HCC group, 80% in
      the metastatic liver cancer group, 31.58% in the liver cirrhosis group, none in
      the chronic hepatitis or acute hepatitis or normal control group, respectively.
      Serum ANXA2 expression in HCC patients was correlated with HBV infection (27.38
      +/- 5.67 ng/mL vs 18.58 +/- 7.83 ng/mL, P < 0.01), extrahepatic metastasis (26.11
      +/- 5.43 ng/mL vs 22.79 +/- 5.64 ng/mL, P < 0.01), and portal vein thrombus
      (26.03 +/- 5.99 ng/mL vs 23.06 +/- 5.03 ng/mL, P < 0.01), and was significantly
      higher (P < 0.01) in the moderately- (26.19 +/- 5.34 ng/mL) or the poorly-
      differentiated group (27.05 +/- 5.13 ng/mL) than in the well differentiated group
      (20.43 +/- 4.97 ng/mL), and in the tumor node metastasis stages III-IV (P < 0.01)
      than in stages I-II. ANXA2 was not correlated with patient sex, age, size or
      alpha-fetoprotein (AFP) level. Area under the receiver operating characteristic
      curve for the whole range of sensitivities and specificities was 0.796 for ANXA2
      and 0.782 for AFP. Combining detection of serum ANXA2 and AFP substantially
      improved the diagnostic efficiency (96.52%) and the negative predictive value
      (96.61%) for HCC. CONCLUSION: The characteristics and distribution of ANXA2
      expression has good diagnostic potential for HCC diagnosis.

PMID- 23139607
TI  - Human thrombin for the treatment of gastric and ectopic varices.
AB  - AIM: To evaluate the efficacy of human thrombin in the treatment of bleeding
      gastric and ectopic varices. METHODS: Retrospective observational study in a
      Tertiary Referral Centre. Between January 1999-October 2005, we identified 37
      patients who were endoscopically treated with human thrombin injection therapy
      for bleeding gastric and ectopic varices. Patient details including age, gender
      and aetiology of liver disease/segmental portal hypertension were documented. The
      thrombin was obtained from the Scottish National Blood Transfusion Service and
      prepared to give a solution of 250 IU/mL which was injected via a standard
      injection needle. All patient case notes were reviewed and the total dose of
      thrombin given along with the number of endoscopy sessions was recorded. Initial
      haemostasis rates, rebleeding rates and mortality were catalogued along with the
      incidence of any immediate complications which could be attributable to the
      thrombin therapy. The duration of follow up was also listed. The study was
      conducted according to the United Kingdom research ethics guidelines. RESULTS:
      Thirty-seven patients were included. 33 patients (89%) had thrombin (250 U/mL)
      for gastric varices, 2 (5.4%) for duodenal varices, 1 for rectal varices and 1
      for gastric and rectal varices. (1) Gastric varices, an average of 15.2 mL of
      thrombin was used per patient. Re-bleeding occurred in 4 patients (10.8%),
      managed in 2 by a transjugular intrahepatic portosystemic shunt (TIPSS) (one
      unsuccessfully who died) and in other 2 by a distal splenorenal shunt; (2)
      Duodenal varices (or type 2 isolated gastric varices), an average of 12.5 mL was
      used per patient over 2-3 endoscopy sessions. Re-bleeding occurred in one
      patient, which was treated by TIPSS; and (3) Rectal varices, an average of 18.3
      mL was used per patient over 3 endoscopy sessions. No re-bleeding occurred in
      this group. CONCLUSION: Human thrombin is a safe, easy to use and effective
      therapeutic option to control haemorrhage from gastric and ectopic varices.

PMID- 23139608
TI  - High-fibre diet and Lactobacillus paracasei B21060 in symptomatic uncomplicated
      diverticular disease.
AB  - AIM: To investigate in symptomatic uncomplicated diverticular disease the
      efficacy of symbiotics associated with a high-fibre diet on abdominal symptoms.
      METHODS: This study was a multicentre, 6-mo randomized, controlled, parallel
      group intervention with a preceding 4-wk washout period. Consecutive outpatients
      with symptomatic uncomplicated diverticular disease, aged 40-80 years, evaluated
      in 4 Gastroenterology Units, were enrolled. Symptomatic uncomplicated
      diverticular disease patients were randomized to two treatment arms A or B.
      Treatment A (n = 24 patients) received 1 symbiotic sachet Flortec((c))
      (Lactobacillus paracasei B21060) once daily plus high-fibre diet for 6 mo.
      Treatment B (n = 21 patients) received high-fibre diet alone for 6 mo. The
      primary endpoint was regression of abdominal symptoms and change of symptom
      severity after 3 and 6 mo of treatment. RESULTS: In group A, the proportion of
      patients with abdominal pain < 24 h decreased from 100% at baseline to 35% and
      25% after 3 and 6 mo, respectively (P < 0.001). In group B the proportion of
      patients with this symptom decreased from 90.5% at baseline to 61.9% and 38.1%
      after 3 and 6 mo, respectively (P = 0.001). Symptom improvement became
      statistically significant at 3 and 6 mo in group A and B, respectively.The
      proportion of patients with abdominal pain >24 h decreased from 60% to 20% then
      5% after 3 and 6 mo, respectively in group A (P < 0.001) and from 33.3% to 9.5%
      at both 3 and 6 mo in group B (P = 0.03). In group A the proportion of patients
      with abdominal bloating significantly decreased from 95% to 60% after 3 mo, and
      remained stable (65%) at 6-mo follow-up (P = 0.005) while in group B, no
      significant changes in abdominal bloating was observed (P = 0.11). After 6 mo of
      treatment, the mean visual analogic scale (VAS) values of both short-lasting
      abdominal pain (VAS, mean +/- SD, group A: 4.6 +/- 2.1 vs 2.2 +/- 0.8, P = 0.02;
      group B: 4.6 +/- 2.9 vs 2.0 +/- 1.9, P = 0.03) and abdominal bloating (VAS, mean
      +/- SD, group A: 5.3 +/- 2.2 vs 3.0 +/- 1.7, P = 0.005; group B: 5.3 +/- 3.2 vs
      2.3 +/- 1.9, P = 0.006) decreased in both groups, whilst the VAS values of
      prolonged abdominal pain decreased in the Flortec((c)) group, but remained
      unchanged in the high-fibre diet group (VAS, mean +/- SD, group A: 6.5 +/- 1.5 vs
      4.5 +/- 2.1, P = 0.052; group B: 4.5 +/- 3.8 vs 5.5 +/- 3.5). CONCLUSION: A high
      fibre diet is effective in relieving abdominal symptoms in symptomatic
      uncomplicated diverticular disease. This treatment may be implemented by
      combining the high-fibre diet with Flortec((c)).

PMID- 23139609
TI  - Effects of the viability of Lactobacillus rhamnosus GG on rotavirus infection in
      neonatal rats.
AB  - AIM: To study the effects of live and dead Lactobacillus rhamnosus GG (GG) on
      rotavirus infection in a neonatal rat model. METHODS: At the age of 2 d, suckling
      Lewis rat pups were supplemented with either live or dead GG and the treatment
      was continued daily throughout the experiment. At the age of 5 and 6 d the pups
      received oral rotavirus (RV) SA-11 strain. The pups were sacrificed at the age of
      7 or 8 d by decapitation. The gastrointestinal tract was removed and macroscopic
      observations were done. The consistency of feces in the colon was classified
      using a four-tier system. RV was detected from the plasma, small intestine, colon
      and feces by real-time quantitative polymerase chain reaction (PCR). RESULTS: In
      this neonatal rat model, RV induced a mild-to-moderate diarrhea in all except one
      pup of the RV-inoculated rats. RV moderately reduced body weight development from
      day 6 onwards. On day 7, after 2 d of RV infection, live and dead GG groups
      gained significantly more weight than the RV group without probiotics [36% (P =
      0.001) and 28% (P = 0.031), respectively]. In addition, when compared with the RV
      control group, both live and dead GG reduced the weight ratio of colon/animal
      body weight to the same level as in the healthy control group, with reductions of
      22% (P = 0.002) and 28% (P < 0.001), respectively. Diarrhea increased moderately
      in both GG groups. However, the diarrhea incidence and severity in the GG groups
      were not statistically significantly different as compared with the RV control
      group. Moreover, observed diarrhea did not provoke weight loss or death. The RV
      control group had the largest amount of RV PCR-positive samples among the RV
      infected groups, and the live GG group had the smallest amount. Rats receiving
      live GG had significantly less RV in the colon (P = 0.027) when compared with the
      RV control group. Live GG was also more effective over dead GG in reducing the
      quantity of RV from plasma (P = 0.047). CONCLUSION: Both live and dead GG have
      beneficial effects in RV infection. GG may increase RV clearance from the body
      and reduce colon swelling.

PMID- 23139610
TI  - Methane production and small intestinal bacterial overgrowth in children living
      in a slum.
AB  - AIM: To analyze small intestinal bacterial overgrowth in school-aged children and
      the relationship between hydrogen and methane production in breath tests.
      METHODS: This transversal study included 85 children residing in a slum and 43
      children from a private school, all aged between 6 and 10 years, in Osasco,
      Brazil. For characterization of the groups, data regarding the socioeconomic
      status and basic housing sanitary conditions were collected. Anthropometric data
      was obtained in children from both groups. All children completed the hydrogen
      (H(2)) and methane (CH(4)) breath test in order to assess small intestinal
      bacterial overgrowth (SIBO). SIBO was diagnosed when there was an increase in
      H(2) >= 20 ppm or CH(4) >= 10 ppm with regard to the fasting value until 60 min
      after lactulose ingestion. RESULTS: Children from the slum group had worse living
      conditions and lower nutritional indices than children from the private school.
      SIBO was found in 30.9% (26/84) of the children from the slum group and in 2.4%
      (1/41) from the private school group (P = 0.0007). Greater hydrogen production in
      the small intestine was observed in children from the slum group when compared to
      children from the private school (P = 0.007). A higher concentration of hydrogen
      in the small intestine (P < 0.001) and in the colon (P < 0.001) was observed
      among the children from the slum group with SIBO when compared to children from
      the slum group without SIBO. Methane production was observed in 63.1% (53/84) of
      the children from the slum group and in 19.5% (8/41) of the children from the
      private school group (P < 0.0001). Methane production was observed in 38/58
      (65.5%) of the children without SIBO and in 15/26 (57.7%) of the children with
      SIBO from the slum. Colonic production of hydrogen was lower in methane-producing
      children (P = 0.017). CONCLUSION: Children who live in inadequate environmental
      conditions are at risk of bacterial overgrowth and methane production. Hydrogen
      is a substrate for methane production in the colon.

PMID- 23139611
TI  - Efficacy of endoluminal gastroplication in Japanese patients with proton pump
      inhibitor-resistant, non-erosive esophagitis.
AB  - AIM: To evaluate the efficacy, safety, and long-term outcomes of endoluminal
      gastroplication (ELGP) in patients with proton pump inhibitor (PPI)-resistant,
      non-erosive reflux disease (NERD). METHODS: The subjects were NERD patients,
      diagnosed by upper endoscopy before PPI use, who had symptoms such as heartburn
      or reflux sensations two or more times a week even after 8 wk of full-dose PPI
      treatment. Prior to ELGP, while continuing full-dose PPI medication, patients'
      symptoms and quality of life (QOL) were assessed using the questionnaire for the
      diagnosis of reflux disease, the frequency scale for symptoms of gastro
      esophageal reflux disease (FSSG), gastrointestinal symptoms rating scale, a 36
      item short-form. In addition, 24-h esophageal pH monitoring or 24-h
      intraesophageal pH/impedance (MII-pH) monitoring was performed. The Bard
      EndoCinch(TM) was used for ELGP, and 2 or 3 plications were made. After ELGP, all
      acid reducers were temporarily discontinued, and medication was resumed depending
      on the development and severity of symptoms. Three mo after ELGP, symptoms, QOL,
      pH or MII-pH monitoring, number of plications, and PPI medication were evaluated.
      Further, symptoms, number of plications, and PPI medication were evaluated 12 mo
      after ELGP to investigate long-term effects. RESULTS: The mean FSSG score
      decreased significantly from before ELGP to 3 and 12 mo after ELGP (19.1 +/- 10.5
      to 10.3 +/- 7.4 and 9.3 +/- 9.9, P < 0.05, respectively). The total number of
      plications decreased gradually at 3 and 12 mo after ELGP (2.4 +/- 0.8 to 1.2 +/-
      0.8 and 0.8 +/- 1.0, P < 0.05, respectively). The FSSG scores in cases with no
      remaining plications and in cases with one or more remaining plications were 4.4
      and 2.7, respectively, after 3 mo, and 2.0 and 2.8, respectively, after 12 mo,
      showing no correlation to plication loss. On pH monitoring, there was no
      difference in the percent time pH < 4 from before ELGP to 3 mo after. Impedance
      monitoring revealed no changes in the number of reflux episodes or the symptom
      index for reflux events from before ELGP to 3 mo after, but the symptom
      sensitivity index decreased significantly 3 mo after ELGP (16.1 +/- 12.9 to 3.9
      +/- 8.3, P < 0.01). At 3 mo after ELGP, 6 patients (31.6%) had reduced their PPI
      medication by 50% or more, and 11 patients (57.9%) were able to discontinue PPI
      medication altogether. After 12 mo, 3 patients (16.7%) were able to reduce the
      amount of PPI medication by 50% or more, and 12 patients (66.7%) were able to
      discontinue PPI medication altogether. A high percentage of cases with remaining
      plications had discontinued PPIs medication after 3 mo, but there was no
      difference after 12 mo. No serious complications were observed in this study.
      CONCLUSION: ELGP was safe, resulted in significant improvement in subjective
      symptoms, and allowed less medication to be used over the long term in patients
      with PPI-refractory NERD.

PMID- 23139612
TI  - Electrogastrography associated with symptomatic changes after prokinetic drug
      treatment for functional dyspepsia.
AB  - AIM: To evaluate the effect of prokinetic drugs on electrogastrography (EGG)
      parameters according to symptomatic changes in patients with functional dyspepsia
      (FD). METHODS: Seventy-four patients with FD were prospectively enrolled in this
      study between December 2006 and December 2010. We surveyed the patients using a
      questionnaire on dyspeptic symptoms before and after an 8-wk course of prokinetic
      drug treatment. We also measured cutaneous pre-prandial and post-prandial EGG
      recordings including percentage of gastric waves (normogastria, bradygastria,
      tachygastria), dominant frequency (DF), dominant power (DP), dominant frequency
      instability coefficient (DFIC), dominant power instability coefficient (DPIC),
      and the ratio of post-prandial to fasting in DP before and after the 8-wk course
      of prokinetic drug treatment. RESULTS: Fifty-two patients (70%) achieved
      symptomatic improvement after prokinetic drug treatment. Patients who had normal
      gastric slow waves showed symptom improvement group after treatment. Post
      prandial DF showed a downward trend in the symptom improvement group, especially
      in the itopride group. Post-prandial DP was increased regardless of symptom
      improvement, especially in the itopride group and mosapride group. Post-prandial
      DFIC and DPIC in the symptom improvement group were significantly increased after
      the treatment. The EGG power ratio was increased after treatment in the symptom
      improvement group (0.50 +/- 0.70 vs 0.93 +/- 1.77, P = 0.002), especially in the
      itopride and levosulpiride groups. CONCLUSION: Prokinetics could improve the
      symptoms of FD by regulating gastric myoelectrical activity, and EGG could be a
      useful tool in evaluating the effects of various prokinetics.

PMID- 23139613
TI  - Comparative study of rendezvous techniques in post-liver transplant biliary
      stricture.
AB  - AIM: To investigate the usefulness of a new rendezvous technique for placing
      stents using the Kumpe (KMP) catheter in angulated or twisted biliary strictures.
      METHODS: The rendezvous technique was performed in patients with a biliary
      stricture after living donor liver transplantation (LDLT) who required the
      exchange of percutaneous transhepatic biliary drainage catheters for inside
      stents. The rendezvous technique was performed using a guidewire in 19 patients
      (guidewire group) and using a KMP catheter in another 19 (KMP catheter group). We
      compared the two groups retrospectively. RESULTS: The baseline characteristics
      did not differ between the groups. The success rate for placing inside stents was
      100% in both groups. A KMP catheter was easier to manipulate than a guidewire.
      The mean procedure time in the KMP catheter group (1012 s, range: 301-2006 s) was
      shorter than that in the guidewire group (2037 s, range: 251-6758 s, P = 0.022).
      The cumulative probabilities corresponding to the procedure time of the two
      groups were significantly different (P = 0.008). The factors related to procedure
      time were the rendezvous technique method, the number of inside stents, the
      operator, and balloon dilation of the stricture (P < 0.05). In a multivariate
      analysis, the rendezvous technique method was the only significant factor related
      to procedure time (P = 0.010). The procedural complications observed included one
      case of mild acute pancreatitis and one case of acute cholangitis in the
      guidewire group, and two cases of mild acute pancreatitis in the KMP catheter
      group. CONCLUSION: The rendezvous technique involving use of the KMP catheter was
      a fast and safe method for placing inside stents in patients with LDLT biliary
      stricture that represents a viable alternative to the guidewire rendezvous
      technique.

PMID- 23139614
TI  - Correlation between mitochondrial TRAP-1 expression and lymph node metastasis in
      colorectal cancer.
AB  - AIM: To evaluate the effect of mitochondrial tumor necrosis factor receptor
      associated protein-1 (TRAP-1) on the lymph node metastasis (LNM) in Chinese
      colorectal cancer (CRC) patients, and develop potential LNM-associated biomarkers
      for CRC using quantitative real-time polymerase chain reaction (RT-PCR) analysis.
      METHODS: Differences in mitochondrial TRAP-1 gene expression between primary CRC
      with LNM (LNM CRC) and without LNM (non-LNM CRC) were assessed in 96 Chinese
      colorectal carcinoma samples using quantitative RT-PCR analysis, Western
      blotting, and confirmed with immunohistochemical assay. The relationship between
      clinicopathological parameters and potential diagnostic biomarkers was also
      examined. RESULTS: TRAP-1 was significantly upregulated in LNM CRC compared with
      non-LNM CRC, which was confirmed by RT-PCR, Western blotting and
      immunohistochemical assay. The expression of TRAP-1 in two different metastatic
      potential human colorectal cancer cell lines, LoVo and HT29, was analyzed with
      Western blotting. The expression level of TRAP-1 was dramatically higher in LoVo
      than in HT29. Overexpression of TRAP-1 was significantly associated with LNM
      (90.2% in LNM group vs 22% in non-LNM group, P < 0.001), the advanced tumor node
      metastasis stage (89.1% in LNM group vs 26.9% in non-LNM group, P < 0.001), the
      increased 5-year recurrence rate (82.7% in LNM group vs 22.6% in non-LNM group, P
      < 0.001) and the decreased 5-year overall survival rate (48.4% in LNM vs 83.2% in
      non-LNM group, P < 0.001). Univariate and multivariate analyses indicated that
      TRAP-1 expression was an independent prognostic factor for recurrence and
      survival of CRC patients (Hazard ratio of 2.445 in recurrence, P = 0.017; 2.867
      in survival, P = 0.028). CONCLUSION: Mitochondria TRAP-1 affects the lymph node
      metastasis in CRC, and may be a potential biomarker for LNM and a prognostic
      factor in CRC. Over-expression of TRAP-1 is a predictive factor for the poor
      outcome of colorectal cancer patients.

PMID- 23139615
TI  - Drug-induced liver injury in hospitalized patients with notably elevated alanine
      aminotransferase.
AB  - AIM: To identify the proportion, causes and the nature of drug-induced liver
      injury (DILI) in patients with notably elevated alanine aminotransferase (ALT).
      METHODS: All the inpatients with ALT levels above 10 times upper limit of normal
      range (ULN) were retrospectively identified from a computerized clinical
      laboratory database at our hospital covering a 12-mo period. Relevant clinical
      information was obtained from medical records. Alternative causes of ALT
      elevations were examined for each patient, including biliary abnormality, viral
      hepatitis, hemodynamic injury, malignancy, DILI or undetermined and other causes.
      All suspected DILI cases were causality assessed using the Council for
      International Organizations of Medical Sciences scale, and only the cases
      classified as highly probable, probable, or possible were diagnosed as DILI.
      Comments related to the diagnosis of DILI in the medical record and in the
      discharge letter for each case were also examined to evaluate DILI detection by
      the treating doctors. RESULTS: A total of 129 cases with ALT > 10 ULN were
      identified. Hemodynamic injury (n = 46, 35.7%), DILI (n = 25, 19.4%) and
      malignancy (n = 21, 16.3%) were the top three causes of liver injury. Peak ALT
      values were lower in DILI patients than in patients with hemodynamic injury (14.5
      +/- 5.6 ULN vs 32.5 +/- 30.7 ULN, P = 0.001). Among DILI patients, one (4%) case
      was classified as definite, 19 (76%) cases were classified as probable and 5
      (20%) as possible according to the CIOMS scale. A hepatocellular pattern was
      observed in 23 (92%) cases and mixed in 2 (8%). The extent of severity of liver
      injury was mild in 21 (84%) patients and moderate in 4 (16%). Before discharge,
      10 (40%) patients were recovered and the other 15 (60%) were improved. The
      improved patients tended to have a higher peak ALT (808 +/- 348 U/L vs 623 +/-
      118 U/L, P = 0.016) and shorter treatment duration before discharge (8 +/- 6 d vs
      28 +/- 12 d, P = 0.008) compared with the recovered patients. Twenty-two drugs
      and 6 herbs were found associated with DILI. Antibacterials were the most common
      agents causing DILI in 8 (32%) cases, followed by glucocorticoids in 6 (24%)
      cases. Twenty-four (96%) cases received treatment of DILI with at least one
      adjunctive drug. Agents for treatment of DILI included anti-inflammatory drugs
      (e.g., glycyrrhizinate), antioxidants (e.g., glutathione, ademetionine 1,4
      butanedisulfonate and tiopronin), polyene phosphatidyl choline and herbal
      extracts (e.g., protoporphyrin disodium and silymarin). Diagnosis of DILI was not
      mentioned in the discharge letter in 60% of the cases. Relative to prevalent
      cases and cases from wards of internal medicine, incident cases and cases from
      surgical wards had a higher risk of missed diagnosis in discharge letter [odds
      ratio (OR) 32.7, 95%CI (2.8-374.1), and OR 58.5, 95%CI (4.6-746.6),
      respectively]. CONCLUSION: DILI is mostly caused by use of antibacterials and
      glucocorticoids, and constitutes about one fifth of hospitalized patients with
      ALT > 10 ULN. DILI is underdiagnosed frequently.

PMID- 23139616
TI  - Dedifferentiated liposarcoma of the rectum: a case report.
AB  - Liposarcoma is one of the most common soft tissue sarcomas found in adults, and
      it usually occurs in the retroperitoneum and the extremities. Here, we describe a
      case of dedifferentiated liposarcoma originating from a well-differentiated
      liposarcoma of the mesorectum that presented as a protruding mass in the rectal
      lumen. Hartmann's operation with total mesorectal excision was performed and the
      tumor was removed radically. No management guidelines are currently available for
      liposarcoma of the rectum. We propose that complete surgical resection be
      required for the treatment of rectal liposarcoma and that a long-term detailed
      follow up is necessary.

PMID- 23139617
TI  - Synchronous double cancers of the common bile duct.
AB  - We report an extremely rare case of synchronous double cancers of the common bile
      duct without pancreaticobiliary maljunction. Only two similar cases have been
      reported in the English literature. Endoscopic re-trograde
      cholangiopancreatography showed a tuberous filling defect in the middle and
      superior parts of the common bile duct, and mild stenosis in the inferior duct.
      Computed tomography (CT) showed a well enhanced mass in the middle and superior
      parts of the common bile duct. A single cancer of the middle and superior bile
      duct was suspected and extra-hepatic bile duct resection was performed. CT eleven
      months after surgery revealed enhanced inferior bile duct wall and a slightly
      enhanced tumor within it. Retrospective review of the CT images taken before
      first surgery showed enhanced inferior bile duct wall without intrabiliary tumor
      only on the delayed phase. The inferior bile duct tumor was suspected to have
      originally co-existed with the middle and superior bile duct tumor.
      Pancreaticoduodenectomy was performed subsequently. Histopathological examination
      revealed that the middle and superior bile duct tumor was a moderately
      differentiated tubular adenocarcinoma while the inferior bile duct tumor was a
      papillary adenocarcinoma. The two tumors were separated and had different
      histological findings and growth patterns, further suggesting that they were two
      primary cancers.

PMID- 23139618
TI  - Mucosal necrosis of the small intestine in myopathy, encephalopathy, lactic
      acidosis, and stroke-like episodes syndrome.
AB  - This report presents a case of massive mucosal necrosis of the small intestine in
      a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and
      stroke-like episodes (MELAS), which particularly affects the brain, nervous
      system and muscles. A 45-year-old Japanese female, with an established diagnosis
      of MELAS, presented with vomiting. Computed tomography showed portomesenteric
      venous gas and pneumatosis intestinalis. She underwent a resection of the small
      intestine. A microscopic study showed necrosis of the mucosa and vacuolar
      degeneration of smooth muscle cells in the arterial wall. Immunohistochemistry
      showed anti-mitochondrial antibody to be highly expressed in the crypts adjacent
      the necrotic mucosa. The microscopic and immunohistochemical findings suggested
      the presence of a large number of abnormal mitochondria in MELAS to be closely
      linked to mucosal necrosis of the small intestine.

PMID- 23139619
TI  - Newly developed autoimmune cholangitis without relapse of autoimmune pancreatitis
      after discontinuing prednisolone.
AB  - A 57-year-old man presented with a 2-wk history of painless jaundice and weight
      loss. He had a large ill-defined enhancing mass-like lesion in the uncinate
      process of the pancreas with stricture of the distal common bile duct. Aspiration
      cytology of the pancreatic mass demonstrated inflammatory cells without evidence
      of malignancy. Total serum immunoglobulin G level was slightly elevated, but IgG4
      level was normal. After the 2-wk 40 mg prednisolone trial, the patient's symptoms
      and bilirubin level improved significantly. A follow-up computed tomography (CT)
      scan showed a dramatic resolution of the pancreatic lesion. A low dose steroid
      was continued. After six months he self-discontinued prednisolone for 3 wk, and
      was presented with jaundice again. A CT scan showed newly developed intrahepatic
      biliary dilatation and marked concentric wall thickening of the common hepatic
      duct and the proximal common bile duct without pancreatic aggravation. The
      patient's IgG4 level was elevated to 2.51 g/L. Prednisolone was started again,
      after which his serum bilirubin level became normal and the thickening of the
      bile duct was resolved. This case suggests that autoimmune pancreatitis can
      progress to other organs that are not involved at the initial diagnosis, even
      with sustained pancreatic remission.

PMID- 23139622
TI  - Upper oesophageal images and Z-line detection with 2 different small-bowel
      capsule systems.
AB  - Transmission of oesophageal images may vary between different small-bowel capsule
      endoscopy models. A retrospective review of 100 examinations performed with 2
      different Small-bowel capsule endoscopy (SBCE) systems (PillCam((r)) and
      MiroCam((r))) was performed. The oral cavity/aero-digestive tract (i.e., tongue,
      uvula and/or epiglottis) was captured/identified in almost all (99%) of
      PillCam((r)) videos but in none of MiroCam((r)) cases, P < 0.0001. Furthermore,
      oesophageal images (i.e., from the upper oesophageal sphincter to the Z-line were
      captured in 99% of PillCam((r)) videos (mean +/- SD, 60.5 +/- 334.1 frames,
      range: 0-3329 frames) and in 66% of MiroCam((r)) cases (mean +/- SD, 11.1 +/-
      46.5 frames, range: 0-382 frames), P < 0.0001. The Z-line was identified in 42%
      of PillCam((r)) videos and 17% of MiroCam((r)), P = 0.0002. This information
      might be useful when performing SBCE in patients with high risks for aspiration.

PMID- 23139620
TI  - Medical treatment for a fish bone-induced ileal micro-perforation: a case report.
AB  - Ingested fish bone induced intestinal perforations are seldom diagnosed
      preoperatively due to incomplete patient history taking and difficulties in image
      evidence identification. Most literature suggests early surgical intervention to
      prevent sepsis and complications resulting from fish bone migrations. We report
      the case of a 44-year-old man suffered from acute abdomen induced by a fish bone
      micro-perforation. The diagnosis was supported by computed tomography (CT)
      imaging of fish bone lodged in distal ileum and a history of fish ingestion
      recalled by the patient. Medical treatment was elected to manage the patient's
      condition instead of surgical intervention. The treatment resulted in a complete
      resolution of abdominal pain on hospital day number 4 without complication.
      Factors affecting clinical treatment decisions include the nature of micro
      perforation, the patient's good overall health condition, and the early diagnosis
      before sepsis signs develop. Micro-perforation means the puncture of intestine
      wall without CT evidence of free air, purulent peritoneum or abscess. We
      subsequently reviewed the literature to support our decision to pursue medical
      instead of surgical intervention.

PMID- 23139621
TI  - Focal peliosis hepatis in a colon cancer patient resembling metastatic liver
      tumor.
AB  - Peliosis hepatis (PH) is a rare benign condition characterized by the presence of
      multiple, randomly distributed, blood filled cystic areas of variable size within
      the liver parenchyma. PH is difficult to recognize and may be mistaken for
      neoplasm, metastases or multiple abscesses. A 75-year-old female with a previous
      history of colon cancer was admitted when a liver mass in the right liver lobe
      was found 11 mo after surgery during the follow-up period. Computed tomography
      and magnetic resonance imaging scan of the abdomen were performed. The initial
      possible diagnosis was metastatic hepatocellular carcinoma. The patient underwent
      excision of the hepatic segment where the nodule was located. The pathological
      diagnosis of the surgical specimen was PH. PH should be considered in the
      differential diagnosis of new liver lesions in patients whose clinical settings
      do not clearly favor metastasization. Clinicians and radiologists must recognize
      these lesions to minimize the probability of misdiagnosis and inappropriate
      treatment.

PMID- 23139623
TI  - Young men's use of aggressive tactics to avoid condom use: A test of a
      theoretical model.
AB  - Although research has demonstrated that men's aggression against women and
      inconsistent condom use are related phenomena, it is little is known as to what
      factors increase risk for aggression to avoid condom use. The present article
      tests a theory-based model of condom avoidance through sexual aggression. Adult
      male participants (N=289) were recruited nationally through online
      advertisements. Aggressive tactics to avoid condom use was measured using an
      adapted version of the revised Sexual Experiences Survey (Abbey et al., 2005) and
      assessed a variety of aggressive behaviors spanning coercion to physical force.
      100 participants (35.3%) reported at least one instance of coercion or aggression
      to avoid using a condom. Structural equation modeling indicated that, attitudes
      towards women, inconsistent condom use, and number of sexual partners were
      significant predictors of aggressive tactics to avoid condom use. A better
      understanding of the attitudinal and behavioral pathways through which men avoid
      condom use through aggressive and coercive means will ultimately result in
      improved education and prevention efforts for at-risk men and women.

PMID- 23139624
TI  - Bioequivalence study of two formulations of bisoprolol fumarate film-coated
      tablets in healthy subjects.
AB  - BACKGROUND: The present study was conducted to compare the bioavailability of two
      bisoprolol fumarate 5 mg film-coated tablet formulations (test and reference
      formulations). PATIENTS AND METHODS: This study was a randomized, single-blind,
      two-period, two-sequence crossover study that included 18 healthy adult male and
      female subjects under fasting condition. The pharmacokinetic parameters were
      determined based on the concentrations of bisoprolol (CAS 66722-44-9), using
      ultraperformance liquid chromatography with a tandem mass spectrometer detector.
      In each of the two study periods (separated by a washout of 1 week) a single dose
      of test or reference product was administered. The pharmacokinetic parameters
      assessed were area under the plasma concentration-time curve from time zero to 48
      hours (AUC(t)), AUC from time zero to infinity (AUC(inf)), the peak plasma
      concentration of the drug (C(max)), time needed to achieve C(max) (t(max)), and
      the elimination half-life (t(1/2)). RESULTS: The geometric mean ratios (90%
      confidence intervals) of the test drug/reference drug for bisoprolol were 101.61%
      (96.14%-107.38%) for AUC(t), 101.31% (95.66%-107.29%) for AUC(inf), and 100.28%
      (93.90%-107.09%) for C(max). The differences between the test and reference drug
      products for bisoprolol t(max) and t(1/2) values were not statistically
      significant (P > 0.05). There was no adverse event encountered during this
      bioequivalence test. The 90% confidence intervals of the test/reference AUC ratio
      and C(max) ratio of bisoprolol were within the acceptance range for
      bioequivalence. CONCLUSION: It was concluded that the two bisoprolol film-coated
      tablet formulations (the test and reference products) were bioequivalent in terms
      of the rate and extent of absorption.

PMID- 23139625
TI  - Penehyclidine hydrochloride: a potential drug for treating COPD by attenuating
      Toll-like receptors.
AB  - BACKGROUND: The aim of this review was to evaluate and summarize the available
      scientific information on penehyclidine hydrochloride (PHC) for the treatment of
      chronic obstructive pulmonary disease (COPD) as a result of its ability to
      attenuate Toll-like receptors. Penehyclidine hydrochloride is an anticholinergic
      drug manufactured in China, with both antimuscarinic and antinicotinic activity.
      PHC is used widely in the clinic as a reversal agent in cases of organic
      phosphorus poisoning and soman poisoning, but also may also have an important
      role as a bronchodilator in the treatment of obstructive airway disease,
      including asthma and, in particular, COPD. METHODS: Our bibliographic sources
      included the CAPLUS, MEDLINE, REGISTRY, CASREACT, CHEMLIST, CHEMCATS, and CNKI
      databases, updated to September 2012. In order to assess the data in detail, we
      used the search terms "penehyclidine hydrochloride," "COPD," "muscarinic
      receptor," and "toll-like receptors." Papers were restricted to those published
      in the English and Chinese languages, and to "paper" and "review" as the document
      type. Patents were also reviewed. RESULTS: Our survey mainly yielded the results
      of research on PHC and the mechanisms of COPD. COPD is a preventable and
      treatable disease with some significant extrapulmonary manifestations that may
      contribute to its severity in some patients. Recently, it has been shown that
      muscarinic receptors may interact with Toll-like receptors. Basic and clinical
      studies of the relationship between the mechanism of action and the effects of
      PHC in the respiratory tract have been studied by a number of laboratories and
      institutions. The main advantages of PHC are that it has few M(2) receptor
      associated cardiovascular side effects and attenuates Toll-like receptors.
      CONCLUSION: PHC may be a promising candidate agent in the treatment of COPD in
      the future because of its ability to attenuate Toll-like receptors. This review
      should be of help to those intending to research this topic further.

PMID- 23139627
TI  - Effect of triiodothyronine (T(3)) augmentation of acute milnacipran
      administration on monoamine levels: an in vivo microdialysis study in rats.
AB  - BACKGROUND: Up to 30% of depressed patients are partially or totally resistant to
      antidepressant therapy. The administration of triiodothyronine (T(3)) to
      antidepressant nonresponders can be an effective augmentation strategy, although
      the mechanism is not fully understood. METHODS: In vivo microdialysis was used to
      examine the effect of T(3) augmentation of the antidepressant, milnacipran. Basal
      extracellular serotonin, norepinephrine, and dopamine levels were measured before
      and after acute milnacipran administration in the medial prefrontal cortex and
      amygdala of rats which had received subchronic (7 days) T(3) treatment or control
      saline. RESULTS: Subchronic administration of T(3) at 0.1 mg/kg significantly
      increased basal extracellular levels of serotonin in the medial prefrontal
      cortex, but not in the amygdala. In contrast, subchronic administration of T(3)
      at 0.2 mg/kg did not alter basal extracellular serotonin levels in the medial
      prefrontal cortex. Basal extracellular levels of norepinephrine and dopamine were
      not modified by either dose of T(3) in either region. Acute administration of
      milnacipran, a serotonin-norepinephrine reuptake inhibitor, to control animals
      resulted in a significant increase of extracellular levels of serotonin,
      norepinephrine, and dopamine. When administered to animals treated subchronically
      with T(3) at 0.1 mg/kg, milnacipran produced an additional increase in
      extracellular serotonin levels but not in levels of norepinephrine or dopamine in
      the medial prefrontal cortex of rats. CONCLUSION: These results suggest that the
      mechanism of the augmentation effect of milnacipran by T(3) administration occurs
      via enhancement of serotonergic neurotransmission, but not through noradrenergic
      or dopaminergic neurotransmission.

PMID- 23139626
TI  - Gemcitabine-loaded liposomes: rationale, potentialities and future perspectives.
AB  - This review describes the strategies used in recent years to improve the
      biopharmaceutical properties of gemcitabine, a nucleoside analog deoxycytidine
      antimetabolite characterized by activity against many kinds of tumors, by means
      of liposomal devices. The main limitation of using this active compound is the
      rapid inactivation of deoxycytidine deaminase following administration in vivo.
      Consequently, different strategies based on its encapsulation/complexation in
      innovative vesicular colloidal carriers have been investigated, with interesting
      results in terms of increased pharmacological activity, plasma half-life, and
      tumor localization, in addition to decreased side effects. This review focuses on
      the specific approaches used, based on the encapsulation of gemcitabine in
      liposomes, with particular attention to the results obtained during the last 5
      years. These approaches represent a valid starting point in the attempt to obtain
      a novel, commercializable drug formulation as already achieved for liposomal
      doxorubicin (Doxil((r)), Caelyx((r))).

PMID- 23139628
TI  - Can headache impair intellectual abilities in children? An observational study.
AB  - BACKGROUND: The purpose of this study was to assess the cognitive functioning of
      children affected by headache, pinpointing the differences in intelligence style
      between subjects affected by migraine without aura and subjects with tension-type
      headache. METHODS: The study population consisted of 147 children (mean age 10.82
      +/- 2.17 years) with headache, recruited from the Headache Center for
      Developmental Age, Child and Adolescent Neuropsychiatry Clinic, Second University
      of Naples. Cognitive profiling was performed using Weschler Intelligence Scale
      for Children Third Edition throughout the sample. According to the International
      Classification of Headache Disorders II criteria for pediatric age, subjects were
      divided into a migraine without aura group (n = 75; 43 boys, 32 girls) and a
      tension-type headache group (n = 72; 49 boys, 23 girls). The results were
      compared with the findings obtained from a sample of 137 healthy control subjects
      recruited from schools in the Campania region, matched for age and gender.
      RESULTS: No difference in full intelligence quotient was found between the
      groups, but the children with tension-type headache had a lower verbal
      intelligence quotient and a higher performance intelligence quotient than the
      healthy controls and children with migraine. Factor analysis data showed that the
      children with migraine seemed to have lower perceptual organization than the
      children affected by tension-type headache. CONCLUSION: To our knowledge, studies
      on cognitive functioning in children affected by headache in the interictal phase
      are scarce, and our results suggest a new perspective in understanding of the
      neuropsychological aspects of young patients affected by headaches.

PMID- 23139629
TI  - Multiple sodium channel variants in the mosquito Culex quinquefasciatus.
AB  - Voltage-gated sodium channels are the target sites of both DDT and pyrethroid
      insecticides. The importance of alternative splicing as a key mechanism governing
      the structural and functional diversity of sodium channels and the resulting
      development of insecticide and acaricide resistance is widely recognized, as
      shown by the extensive research on characterizing alternative splicing and
      variants of sodium channels in medically and agriculturally important insect
      species. Here we present the first comparative study of multiple variants of the
      sodium channel transcripts in the mosquito Culex quinquefasciatus. The variants
      were classified into two categories, CxNa-L and CxNa-S based on their
      distinguishing sequence sizes of ~6.5 kb and ~4.0 kb, respectively, and generated
      via major extensive alternative splicing with minor small deletions/ insertions
      in susceptible S-Lab, low resistant HAmCq(G0), and highly resistant
      HAmCq(G8)Culex strains. Four alternative Cx-Na-L splice variants were identified,
      including three full length variants with three optional exons (2, 5, and 21i)
      and one with in-frame-stop codons. Large, multi-exon-alternative splices were
      identified in the CxNa-S category. All CxNa-S splicing variants in the S-Lab and
      HAmCq(G0) strains contained in-frame stop codons, suggesting that any resulting
      proteins would be truncated. The ~1000 to ~3000-fold lower expression of these
      splice variants with stop codons compared with the CxNa-L splicing variants may
      support the lower importance of these variants in S-Lab and HAmCq(G0).
      Interestingly, two alternative splicing variants of CxNa-S in HAmCq(G8) included
      entire ORFs but lacked exons 5 to18 and these two variants had much higher
      expression levels in HAmCq(G8) than in S-Lab and HAmCq(G0). These results provide
      a functional basis for further characterizing how alternative splicing of a
      voltage-gated sodium channel contributes to diversity in neuronal signaling in
      mosquitoes in response to pyrethroids, and possibly indicates the role of these
      variants in the development of pyrethroid resistance.

PMID- 23139630
TI  - Collagen XXIV (Col24alpha1) promotes osteoblastic differentiation and
      mineralization through TGF-beta/Smads signaling pathway.
AB  - Collagen XXIV (Col24alpha1) is a recently discovered fibrillar collagen. It is
      known that mouse Col24alpha1 is predominantly expressed in the forming skeleton
      of the mouse embryo, as well as in the trabecular bone and periosteum of the
      newborn mouse. However, the role and mechanism of Col24alpha1 in osteoblast
      differentiation and mineralization remains unclear. By analyzing the expression
      pattern of Col24alpha1, we confirmed that it is primarily expressed in bone
      tissues, and this expression gradually increased concomitant with the progression
      of osteoblast differentiation. Through the use of a lentivirus vector-mediated
      interference system, silencing Col24alpha1 expression in MC3T3-E1 murine
      preosteoblastic cells resulted in significant inhibition of alkaline phosphatase
      (ALP) activity, cell mineralization, and the expression of osteoblast marker
      genes such as runt-related transcription factor 2 (Runx2), osteocalcin (OCN),
      ALP, and type I collagen (Col I). Subsequent overexpression not only rescued the
      deficiency in osteoblast differentiation from Col24alpha1 silenced cells, but
      also enhanced osteoblastic differentiation in control cells. We further revealed
      that Col24alpha1 interacts with integrin beta3, and silencing Col24alpha1 up
      regulated the expression of Smad7 during osteoblast differentiation while at the
      same time inhibiting the phosphorylation of the Smad2/3 complex. These results
      suggest that Col24alpha1 imparts some of its regulatory control on osteoblast
      differentiation and mineralization at least partially through interaction with
      integrin beta3 and the transforming growth factor beta (TGF-beta) /Smads
      signaling pathway.

PMID- 23139631
TI  - Characterization of a chitin synthase encoding gene and effect of diflubenzuron
      in soybean aphid, Aphis glycines.
AB  - Chitin synthases are critical enzymes for synthesis of chitin and thus for
      subsequent growth and development in insects. We identified the cDNA of chitin
      synthase gene (CHS) in Aphis glycines, the soybean aphid, which is a serious pest
      of soybean. The full-length cDNA of CHS in A. glycines (AyCHS) was 5802 bp long
      with an open reading frame of 4704 bp that encoded for a 1567 amino acid residues
      protein. The predicted AyCHS protein had a molecular mass of 180.05 kDa and its
      amino acid sequence contained all the signature motifs (EDR, QRRRW and TWGTR) of
      chitin synthases. The quantitative real-time PCR (qPCR) analysis revealed that
      AyCHS was expressed in all major tissues (gut, fat body and integument); however,
      it had the highest expression in integument (~3.5 fold compared to gut).
      Interestingly, the expression of AyCHS in developing embryos was nearly 7 fold
      higher compared to adult integument, which probably is a reflection of embryonic
      molts in hemimetabolus insects. Expression analysis in different developmental
      stages of A. glycines revealed a consistent AyCHS expression in all stages.
      Further, through leaf dip bioassay, we tested the effect of diflubenzuron (DFB,
      Dimilin (r)), a chitin-synthesis inhibitor, on A. glycines' survival, fecundity
      and body weight. When fed with soybean leaves previously dipped in 50 ppm DFB
      solution, A. glycines nymphs suffered significantly higher mortality compared to
      control. A. glycines nymphs feeding on diflubenzuron treated leaves showed a
      slightly enhanced expression (1.67 fold) of AyCHS compared to nymphs on untreated
      leaves. We discussed the potential applications of the current study to develop
      novel management strategies using chitin-synthesis inhibitors and using RNAi by
      knocking down AyCHS expression.

PMID- 23139632
TI  - Stem cell transplantation increases antioxidant effects in diabetic mice.
AB  - Intra bone marrow-bone marrow transplantation (IBM- BMT) + thymus transplantation
      (TT) has been shown to reduce the incidence of graft versus host disease (GVHD)
      and restore donor-derived T cell function. In addition, an increase in insulin
      sensitivity occurred in db/db mice after IBM-BMT+TT treatment. Heme oxygenase
      (HO)-1 is a stress inducible enzyme which exert antioxidant, antiapoptotic, and
      immune-modulating properties. We examined whether IBM-BMT+TT could modulate the
      expression of HO-1 in the kidneys of db/db mice. Six-week-old db/db mice with
      blood glucose levels higher than 250 mg/dl were treated with IBM-BMT+TT. Six
      weeks later, the db/db mice showed decreased body weight, blood glucose levels
      and insulin, and increased plasma adiponectin levels. The upregulation of HO-1
      was associated with significantly (p<0.05) increased levels of peNOS and pAKT,
      but decreased levels of iNOS in the kidneys of db/db mice. Plasma creatinine
      levels also decreased (p<0.05), and the expression of type IV collagen was
      improved. Thus IBM-BMT+TT unregulated the expression of HO-1, peNOS and pAKT,
      while decreasing iNOS levels in the kidney of db/db mice. This was associated
      with an improvement in renal function.

PMID- 23139633
TI  - Protective effect of grape seed proanthocyanidins against liver ischemic
      reperfusion injury: particularly in diet-induced obese mice.
AB  - BACKGROUND: Hepatic ischemia and reperfusion injury (IRI) is a major complication
      in liver surgery, and hepatic steatosis is a primary factor aggravating cellular
      injury during IRI. Both pro-inflammatory cytokines and reactive oxygen species
      (ROS) are key mediators of hepatic IRI. Ischemic preconditioning (IpreC), remote
      ischemia preconditioning (RIPC) and ischemic postconditioning (IpostC) have
      offered protections on hepatic IRI, but all these methods have their own
      shortcomings. Grape seed proanthocyanidins (GSP) has a broad spectrum of
      pharmacological properties against oxidative stress. Thus, GSP has potential
      protective effects against hepatic IRI. METHODS: C57BL/6 mice suffering 30mins
      hepatic ischemia process were sacrificed after 1h reperfusion to build murine
      warm hepatic IRI model. The mice were injected GSP intraperitoneally 10, 20,
      40mg/kg/day for 3 weeks as pharmacological preconditioning. Obese mice fed with
      high-fat diet for 24 weeks before used. Three pathways related to IRI, including
      ROS elimination, pro-inflammatory cytokines release and hypoxia responses were
      examined. RESULTS: Our data show that GSP could significantly reduce hepatic IRI
      by protecting hepatocyte function and increasing the activity of ROS scavengers,
      as well as decreasing cytokines levels. At the same time, GSP also enhance the
      hypoxia tolerance response. Combined GSP and postconditioning can provided
      synergistic protection. In the obese mice suffering hepatic IRI group, GSP was
      more effective than postconditioning on protecting liver against IRI, and the
      combined strategy was obviously superior to the solo treatment. CONCLUSION: GSP
      could protect liver against IRI: particularly in high-fat diet induced obese
      mice. GSP used as pharmacological preconditioning and combined with other
      protocols have huge potential to be used in clinical.

PMID- 23139634
TI  - Identification of metastamirs as metastasis-associated microRNAs in clear cell
      renal cell carcinomas.
AB  - MicroRNAs (miRNAs) play a pivotal role in cancerogenesis and cancer progression,
      but their specific role in the metastasis of clear cell renal cell carcinomas
      (ccRCC) is still limited. Based on microRNA microarray analyses from normal and
      cancerous samples of ccRCC specimens and from bone metastases of ccRCC patients,
      we identified a set of 57 differentially expressed microRNAs between these three
      sample groups of ccRCC. A selected panel of 33 miRNAs was subsequently validated
      by RT-qPCR on total 57 samples. Then, 30 of the 33 examined miRNAs were confirmed
      to be deregulated. A stepwise down-regulation of miRNA expression from normal,
      over primary tumor to metastatic tissue samples, was found to be typical. A total
      of 23 miRNAs (miR-10b/-19a/-19b/-20a/-29a/-29b/-29c/-100/-101/-126/-127/-130/
      141/-143/-145/-148a/-192/-194/-200c/-210/-215/-370/-514) were down-regulated in
      metastatic tissue samples compared with normal tissue. This down-regulated
      expression in metastatic tissue in comparison with primary tumor tissue was also
      present in 21 miRNAs. In cell culture experiments with 5-aza-2'-deoxycytidine and
      trichostatin A, epigenetic modifications were shown as one reason of this down
      regulation. The altered miRNA profiles, comprising newly identified metastasis
      associated miRNAs, termed metastamir and the predicted miRNA-target interactions
      together with the significant correlations of miRNAs that were either lost or
      newly appeared in the studied sample groups, afford a solid basis for further
      functional analyses of individual miRNAs in RCC metastatic progression.

PMID- 23139635
TI  - Rhein protects against obesity and related metabolic disorders through liver X
      receptor-mediated uncoupling protein 1 upregulation in brown adipose tissue.
AB  - Liver X receptors (LXRs) play important roles in regulating cholesterol
      homeostasis, and lipid and energy metabolism. Therefore, LXR ligands could be
      used for the management of metabolic disorders. We evaluated rhein, a natural
      compound from Rheum palmatum L., as an antagonist for LXRs and investigated its
      anti-obesity mechanism in high-fat diet-fed mice. Surface plasmon resonance
      assays were performed to examine the direct binding of rhein to LXRs. LXR target
      gene expression was assessed in 3T3-L1 adipocytes and HepG2 hepatic cells in
      vitro. C57BL/6J mice fed a high-fat diet were orally administered with rhein for
      4 weeks, and then the expression levels of LXR-related genes were analyzed. Rhein
      bound directly to LXRs. The expression levels of LXR target genes were suppressed
      by rhein in 3T3-L1 and HepG2 cells. In white adipose tissue, muscle and liver,
      rhein reprogrammed the expression of LXR target genes related to adipogenesis and
      cholesterol metabolism. Rhein activated uncoupling protein 1 (UCP1) expression in
      brown adipose tissue (BAT) in wild-type mice, but did not affect UCP1 expression
      in LXR knockout mice. In HIB-1B brown adipocytes, rhein activated the UCP1 gene
      by antagonizing the repressive effect of LXR on UCP1 expression. This study
      suggests that rhein may protect against obesity and related metabolic disorders
      through LXR antagonism and regulation of UCP1 expression in BAT.

PMID- 23139637
TI  - TRAF family member-associated NF-kappaB activator (TANK) induced by RANKL
      negatively regulates osteoclasts survival and function.
AB  - Osteoclasts are the principle bone-resorbing cells. Precise control of balanced
      osteoclast activity is indispensable for bone homeostasis. Osteoclast activation
      mediated by RANK-TRAF6 axis has been clearly identified. However, a negative
      regulation-machinery in osteoclast remains unclear. TRAF family member-associated
      NF-kappaB activator (TANK) is induced by about 10 folds during
      osteoclastogenesis, according to a genome-wide analysis of gene expression before
      and after osteoclast maturation, and confirmed by western blot and quantitative
      RT-PCR. Bone marrow macrophages (BMMs) transduced with lentivirus carrying tank
      shRNA were induced to form osteoclast in the presence of RANKL and M-CSF. Tank
      expression was downregulated by 90% by Tank-shRNA, which is confirmed by western
      blot. Compared with wild-type (WT) cells, osteoclastogenesis of Tank-silenced
      BMMs was increased, according to tartrate-resistant acid phosphatase (TRAP) stain
      on day 5 and day 7. Number of bone resorption pits by Tank-silenced osteoclasts
      was increased by 176% compared with WT cells, as shown by wheat germ agglutinin
      (WGA) stain and scanning electronic microscope (SEM) analysis. Survival rate of
      Tank-silenced mature osteoclast is also increased. However, acid production of
      Tank-knockdown cells was not changed compared with control cells. IkappaBalpha
      phosphorylation is increased in tank-silenced cells, indicating that TANK may
      negatively regulate NF-kappaB activity in osteoclast. In conclusion, Tank, whose
      expression is increased during osteoclastogenesis, inhibits osteoclast formation,
      activity and survival, by regulating NF-kappaB activity and c-FLIP expression.
      Tank enrolls itself in a negative feedback loop in bone resorption. These results
      may provide means for therapeutic intervention in diseases of excessive bone
      resorption.

PMID- 23139638
TI  - The Role of Masculine Norms and Informal Support on Mental Health in Incarcerated
      Men.
AB  - Mental health problems, in general, and major depression in particular, are
      prevalent among incarcerated men. It is estimated that 23% of state inmates
      report experiencing symptoms of major depression. Despite the high rates of
      depressive symptoms, there is little understanding about the psychosocial factors
      that are associated with depressive and anxiety symptoms of incarcerated men. One
      factor relevant to the mental health of incarcerated men is their adherence to
      traditional masculine norms. We investigated the role of masculine norms and
      informal support on depressive and anxiety symptoms among 123 incarcerated men.
      The results revealed that adherence to the masculine norm of emotional control
      were negatively associated with depressive symptoms while heterosexual
      presentation and informal support were related to both depressive and anxiety
      symptoms. High levels of reported informal support moderated the effects of
      heterosexual presentation on depressive and anxiety symptoms. Public health and
      clinical implications are discussed.

PMID- 23139636
TI  - Regulation of the SRC family kinases by Csk.
AB  - The non-receptor tyrosine kinase Csk serves as an indispensable negative
      regulator of the Src family tyrosine kinases (SFKs) by specifically
      phosphorylating the negative regulatory site of SFKs, thereby suppressing their
      oncogenic potential. Csk is primarily regulated through its SH2 domain, which is
      required for membrane translocation of Csk via binding to scaffold proteins such
      as Cbp/PAG1. The binding of scaffolds to the SH2 domain can also upregulate Csk
      kinase activity. These regulatory features have been elucidated by analyses of
      Csk structure at the atomic levels. Although Csk itself may not be mutated in
      human cancers, perturbation of the regulatory system consisting of Csk, Cbp/PAG1,
      or other scaffolds, and certain tyrosine phosphatases may explain the
      upregulation of SFKs frequently observed in human cancers. This review focuses on
      the molecular bases for the function, structure, and regulation of Csk as a
      unique regulatory tyrosine kinase for SFKs.

PMID- 23139639
TI  - CBOL protist working group: barcoding eukaryotic richness beyond the animal,
      plant, and fungal kingdoms.

PMID- 23139641
TI  - Natural selection molds genomic insulator elements.

PMID- 23139640
TI  - Adaptive evolution and the birth of CTCF binding sites in the Drosophila genome.
AB  - Changes in the physical interaction between cis-regulatory DNA sequences and
      proteins drive the evolution of gene expression. However, it has proven difficult
      to accurately quantify evolutionary rates of such binding change or to estimate
      the relative effects of selection and drift in shaping the binding evolution.
      Here we examine the genome-wide binding of CTCF in four species of Drosophila
      separated by between ~2.5 and 25 million years. CTCF is a highly conserved
      protein known to be associated with insulator sequences in the genomes of human
      and Drosophila. Although the binding preference for CTCF is highly conserved, we
      find that CTCF binding itself is highly evolutionarily dynamic and has adaptively
      evolved. Between species, binding divergence increased linearly with evolutionary
      distance, and CTCF binding profiles are diverging rapidly at the rate of 2.22%
      per million years (Myr). At least 89 new CTCF binding sites have originated in
      the Drosophila melanogaster genome since the most recent common ancestor with
      Drosophila simulans. Comparing these data to genome sequence data from 37
      different strains of Drosophila melanogaster, we detected signatures of selection
      in both newly gained and evolutionarily conserved binding sites. Newly evolved
      CTCF binding sites show a significantly stronger signature for positive selection
      than older sites. Comparative gene expression profiling revealed that expression
      divergence of genes adjacent to CTCF binding site is significantly associated
      with the gain and loss of CTCF binding. Further, the birth of new genes is
      associated with the birth of new CTCF binding sites. Our data indicate that
      binding of Drosophila CTCF protein has evolved under natural selection, and CTCF
      binding evolution has shaped both the evolution of gene expression and genome
      evolution during the birth of new genes.

PMID- 23139642
TI  - Leisure time physical activity of moderate to vigorous intensity and mortality: a
      large pooled cohort analysis.
AB  - BACKGROUND: Leisure time physical activity reduces the risk of premature
      mortality, but the years of life expectancy gained at different levels remains
      unclear. Our objective was to determine the years of life gained after age 40
      associated with various levels of physical activity, both overall and according
      to body mass index (BMI) groups, in a large pooled analysis. METHODS AND
      FINDINGS: We examined the association of leisure time physical activity with
      mortality during follow-up in pooled data from six prospective cohort studies in
      the National Cancer Institute Cohort Consortium, comprising 654,827 individuals,
      21-90 y of age. Physical activity was categorized by metabolic equivalent hours
      per week (MET-h/wk). Life expectancies and years of life gained/lost were
      calculated using direct adjusted survival curves (for participants 40+ years of
      age), with 95% confidence intervals (CIs) derived by bootstrap. The study
      includes a median 10 y of follow-up and 82,465 deaths. A physical activity level
      of 0.1-3.74 MET-h/wk, equivalent to brisk walking for up to 75 min/wk, was
      associated with a gain of 1.8 (95% CI: 1.6-2.0) y in life expectancy relative to
      no leisure time activity (0 MET-h/wk). Higher levels of physical activity were
      associated with greater gains in life expectancy, with a gain of 4.5 (95% CI: 4.3
      4.7) y at the highest level (22.5+ MET-h/wk, equivalent to brisk walking for 450+
      min/wk). Substantial gains were also observed in each BMI group. In joint
      analyses, being active (7.5+ MET-h/wk) and normal weight (BMI 18.5-24.9) was
      associated with a gain of 7.2 (95% CI: 6.5-7.9) y of life compared to being
      inactive (0 MET-h/wk) and obese (BMI 35.0+). A limitation was that physical
      activity and BMI were ascertained by self report. CONCLUSIONS: More leisure time
      physical activity was associated with longer life expectancy across a range of
      activity levels and BMI groups. Please see later in the article for the Editors'
      Summary.

PMID- 23139643
TI  - The Brazil SimSmoke policy simulation model: the effect of strong tobacco control
      policies on smoking prevalence and smoking-attributable deaths in a middle income
      nation.
AB  - BACKGROUND: Brazil has reduced its smoking rate by about 50% in the last 20 y.
      During that time period, strong tobacco control policies were implemented. This
      paper estimates the effect of these stricter policies on smoking prevalence and
      associated premature mortality, and the effect that additional policies may have.
      METHODS AND FINDINGS: The model was developed using the SimSmoke tobacco control
      policy model. Using policy, population, and smoking data for Brazil, the model
      assesses the effect on premature deaths of cigarette taxes, smoke-free air laws,
      mass media campaigns, marketing restrictions, packaging requirements, cessation
      treatment programs, and youth access restrictions. We estimate the effect of past
      policies relative to a counterfactual of policies kept to 1989 levels, and the
      effect of stricter future policies. Male and female smoking prevalence in Brazil
      have fallen by about half since 1989, which represents a 46% (lower and upper
      bounds: 28%-66%) relative reduction compared to the 2010 prevalence under the
      counterfactual scenario of policies held to 1989 levels. Almost half of that 46%
      reduction is explained by price increases, 14% by smoke-free air laws, 14% by
      marketing restrictions, 8% by health warnings, 6% by mass media campaigns, and
      10% by cessation treatment programs. As a result of the past policies, a total of
      almost 420,000 (260,000-715,000) deaths had been averted by 2010, increasing to
      almost 7 million (4.5 million-10.3 million) deaths projected by 2050. Comparing
      future implementation of a set of stricter policies to a scenario with 2010
      policies held constant, smoking prevalence by 2050 could be reduced by another
      39% (29%-54%), and 1.3 million (0.9 million-2.0 million) out of 9 million future
      premature deaths could be averted. CONCLUSIONS: Brazil provides one of the
      outstanding public health success stories in reducing deaths due to smoking, and
      serves as a model for other low and middle income nations. However, a set of
      stricter policies could further reduce smoking and save many additional lives.
      Please see later in the article for the Editors' Summary.

PMID- 23139644
TI  - Chinese-style decentralization and health system reform.

PMID- 23139645
TI  - Exploring residue component contributions to dynamical network models of
      allostery.
AB  - Allosteric regulation in biological systems is of considerable interest given the
      vast number of proteins that exhibit such behavior. Network models obtained from
      molecular dynamics simulations have been shown to be powerful tools for the
      analysis of allostery. In this work, different coarse-grain residue
      representations (nodes) are used together with a dynamical network model to
      investigate models of allosteric regulation. This model assumes that allosteric
      signals are dependent on positional correlations of protein substituents, as
      determined through molecular dynamics simulations, and uses correlated motion to
      generate a signaling weight between two given nodes. We examine four types of
      network models using different node representations in Cartesian coordinates: the
      (i) residue alpha-carbons, (ii) sidechain center of mass, (iii) backbone center
      of mass, and the entire (iv) residue center of mass. All correlations are
      filtered by a dynamic contact map that defines the allowable interactions between
      nodes based on physical proximity. We apply the four models to imidazole glycerol
      phosphate synthase (IGPS), which provides a well-studied experimental framework
      in which allosteric communication is known to persist across disparate protein
      domains (e.g. a protein dimer interface). IGPS is modeled as a network of nodes
      and weighted edges. Optimal allosteric pathways are traced using the Floyd
      Warshall algorithm for weighted networks, and community analysis (a form of
      hierarchical clustering) is performed using the Girvan-Newman algorithm. Our
      results show that dynamical information encoded in the residue center of mass
      must be included in order to detect residues that are experimentally known to
      play a role in allosteric communication for IGPS. More broadly, this new method
      may be useful for predicting pathways of allosteric communication for any
      biomolecular system in atomic detail.

PMID- 23139646
TI  - Making Sense of Extreme Longevity: Explorations Into the Spiritual Lives of
      Centenarians.
AB  - As the population grows older and more individuals live into advanced age the
      oldest-old segment will continue to increase in size. This qualitative study
      analyzes data gathered using in-depth interviewing and explores the spiritual
      saliency for sixteen centenarians. Results illustrate the importance spirituality
      has for older adults over the lifecourse, particularly those in advanced age. Our
      findings indicate that spirituality is key factor of support, an important
      resource in late life, and maintains continuity over the lifecourse for the
      centenarians. Additionally, spirituality serves as critical component in the
      everyday lives of the participants and provide a framework for helping older
      adults make sense of having lived a very long life. The findings reported here
      support the need for researchers and practitioners to consider the importance of
      spirituality in late life, particularly for those in their last decades.

PMID- 23139647
TI  - Implantable Microprobe with Arrayed Microsensors for Combined Amperometric
      Monitoring of the Neurotransmitters, Glutamate and Dopamine.
AB  - An implantable, micromachined microprobe with a microsensor array for combined
      monitoring of the neurotransmitters, glutamate (Glut) and dopamine (DA), by
      constant potential amperometry has been created and characterized. Microprobe
      studies in vitro revealed Glut and DA microsensor sensitivities of 126+/-5
      nA.MUM(-1).cm(-2) and 3250+/-50 nA.MUM(-1).cm(-2), respectively, with
      corresponding detection limits of 2.1+/-0.2 MUM and 62+/-8 nM, both at comparable
      ~1 sec response times. No diffusional interaction of H(2)O(2) among arrayed
      microelectrodes was observed. Also, no responses from the electroactive
      interferents, ascorbic acid (AA), uric acid (UA), DOPA (a DA catabolite) or DOPAC
      (a DA precursor), over their respective physiological concentration ranges, were
      detected. The dual sensing microbe attributes of size, detection limit,
      sensitivity, response time and selectivity make it attractive for combined
      sensing of Glut and DA in vivo.

PMID- 23139648
TI  - Serum UPLC-MS/MS metabolic profiling in an experimental model for acute-liver
      injury reveals potential biomarkers for hepatotoxicity.
AB  - A key interest in clinical diagnosis and pharmaceutical industry is to have a
      repertoire of noninvasive biomarkers to-individually or in combination-be able to
      infer or predict the degree of liver injury caused by pathological conditions or
      drugs. Metabolomics-a comprehensive study of global metabolites-has become a
      highly sensitive and powerful tool for biomarker discovery thanks to recent
      technological advances. An ultra-performance liquid chromatography/time-of-flight
      tandem mass spectrometry (UPLC/TOF MS/MS)-based metabolomics approach was
      employed to investigate sera from galactosamine-treated rats to find potential
      biomarkers for acute liver injury. Hepatic damage was quantified by determining
      serum transaminase activity and in situ liver histological lesions. Principal
      component analysis in combination with coefficient of correlation analysis was
      used for biomarker selection and identification. According to the data, serum
      levels of several metabolites including glucose, amino acids, and membrane lipids
      were significantly modified, some of them showing a high correlation with the
      degree of liver damage determined by histological examination of the livers. In
      conclusion, this study supports that UPLC-MS/MS based serum metabolomics in
      experimental animal models could be a powerful approach to search for biomarkers
      for drug- or disease-induced liver injury.

PMID- 23139650
TI  - Lymphoepithelial cyst of the pancreas.
AB  - Cystic lesions of the pancreas can be divided into true cysts, pseudocysts, and
      cystic neoplasms. Lymphoepithelial cysts (LECs) are a type of true cyst that can
      mimic pseudocysts and cystic neoplasms. LECs are rare lesions; fewer than 90
      cases have been reported in the English language literature. The case of a 60
      year-old man with an LEC of the pancreas is reported. He was admitted with upper
      abdominal discomfort. Computed tomography showed a 64 * 39 mm cystic mass in the
      retroperitoneum behind the duodenum and inferior caval vein. Magnetic resonance
      imaging revealed a right-sided mass on T1-weighted imaging, with a clear boundary
      between the mass and its surroundings, except for the pancreas. The mass had an
      inhomogeneous intensity on T2-weighted imaging. Within the mass, small floating
      nodules with low intensity were seen. Endoscopic ultrasound showed many high
      echoic nodules and smaller grains scattered everywhere in the mass. Fine needle
      aspiration and cytologic examination were performed. Characteristic chylaceous
      fluid was obtained in which anucleate squamous cells were found. There were also
      a few atypical large cells with irregularly shaped marked nucleoli and
      degenerative cytoplasm. Cytologic diagnosis was suspicious for malignancy. The
      lesion was diagnosed as a retroperitoneal cyst, probably of pancreatic origin.
      Since a neoplastic lesion could not be ruled out, surgery was performed. The
      lesion was palpable on the dorsal side of the second portion of the duodenum. The
      mass was completely resected. Macroscopically, the lesion was a multilocular cyst
      with a thin septal wall. The cyst was filled with cottage cheese-like substance.
      Microscopically, the cyst wall was composed of stratified squamous epithelium and
      dense subepithelial lymphatic tissue with developed lymph follicles. The
      epithelial cells had no atypia. The histopathologic diagnosis was LEC of the
      pancreas. The patient's postoperative course was good.

PMID- 23139649
TI  - Changes in dietary habits after migration and consequences for health: a focus on
      South Asians in Europe.
AB  - BACKGROUND: Immigrants from low-income countries comprise an increasing
      proportion of the population in Europe. Higher prevalence of obesity and
      nutrition related diseases, such as type 2 diabetes (T2D) and cardiovascular
      disease (CVD) is found in some immigrant groups, especially in South Asians. AIM:
      To review dietary changes after migration and discuss the implication for health
      and prevention among immigrants from low-income countries to Europe, with a
      special focus on South Asians. METHOD: Systematic searches in PubMed were
      performed to identify relevant high quality review articles and primary research
      papers. The searches were limited to major immigrant groups in Europe, including
      those from South Asia (India, Pakistan, Bangladesh, Sri Lanka). Articles in
      English from 1990 and onwards from Europe were included. For health implications,
      recent review articles and studies of particular relevance to dietary changes
      among South Asian migrants in Europe were chosen. RESULTS: Most studies report on
      dietary changes and health consequences in South Asians. The picture of dietary
      change is complex, depending on a variety of factors related to country of
      origin, urban/rural residence, socio-economic and cultural factors and situation
      in host country. However, the main dietary trend after migration is a substantial
      increase in energy and fat intake, a reduction in carbohydrates and a switch from
      whole grains and pulses to more refined sources of carbohydrates, resulting in a
      low intake of fiber. The data also indicate an increase in intake of meat and
      dairy foods. Some groups have also reduced their vegetable intake. The findings
      suggest that these dietary changes may all have contributed to higher risk of
      obesity, T2D and CVD.  IMPLICATIONS FOR PREVENTION: A first priority in
      prevention should be adoption of a low-energy density - high fiber diet, rich in
      whole grains and grain products, as well as fruits, vegetables and pulses.
      Furthermore, avoidance of energy dense and hyperprocessed foods is an important
      preventive measure.

PMID- 23139651
TI  - Successful surgical control of peritoneal dissemination of hepatocellular
      carcinoma.
AB  - Treatment for the peritoneal dissemination of hepatocellular carcinoma (HCC) has
      not yet been established. We report a patient with HCC associated with
      disseminated intra-abdominal tumor. A 74-year-old man was admitted to our
      hospital. Computed tomography showed a 3 * 3 cm mass in the left hepatic lobe and
      a giant mass between the stomach and spleen. At laparotomy, the tumor was seen in
      the medial segment and evaginated to the diaphragm. There was a tumor between the
      stomach and spleen, confirmed as a 5 * 5 cm tumor evaginated from the left
      diaphragm, and a 7 * 7 cm tumor adhesive to the spleen. These two tumors were not
      continuous and were separated. Furthermore, we confirmed a 10 * 10 cm tumor in
      the pelvic cavity. We performed partial hepatectomy, resection of the tumor
      evaginated from the diaphragm, resection of the tumor of the spleen and tail of
      pancreas, and resection of the tumor in the pelvic cavity. Histopathologically,
      all resected tumors were confirmed to be well-differentiated HCC. HCC rarely
      disseminates intraperitoneally. It is considered that the peritoneal
      dissemination of HCC occurred from poorly differentiated or undifferentiated
      type. Then this report is a rare case. Although surgical treatment of peritoneal
      dissemination of HCC is not curative, surgery may improve survival and provide
      good quality of life in selected cases.

PMID- 23139652
TI  - Severe recurrent achalasia cardia responding to treatment of severe autoimmune
      acquired haemophilia.
AB  - Acquired haemophilia A and severe acquired achalasia are both very rare
      conditions with unknown aetiology. Haemophilia A is a haemorrhagic disease
      induced by deficiency or malfunction of coagulation factor VIII. Congenital
      haemophilia is an inherited disease transmitted by the mother through X-linked
      inheritance and primarily affects males. However, acquired haemophilia A is a
      serious, sudden-onset, autoimmune disease that affects either sex. In addition,
      achalasia is a disease of the oesophagus caused by abnormal function of the
      nerves and muscles. It causes swallowing difficulties due to the inability of the
      lower oesophageal sphincter to relax during swallowing, leading to dysphagia,
      regurgitation and chest pain. In this report, we describe the case of a patient
      with severe, newly diagnosed, acquired haemophilia A with long-standing,
      recurrent achalasia; the achalasia had recurred 3 times despite complete and
      proper surgical fixation. Acquired haemophilia A is treated with
      immunosuppressive therapy. High-dose steroid therapy was administered for 7
      months, during which the patient responded well; moreover, the achalasia did not
      recur for more than 2 years. The response of the achalasia to immunosuppressive
      therapy suggests that achalasia may be an autoimmune disorder and that there may
      be an association between both diseases. The findings of the present case suggest
      that achalasia may favourably respond to steroid therapy as a first-line
      treatment prior to surgery.

PMID- 23139653
TI  - Laparoscopic splenectomy for traumatic splenic injury after screening
      colonoscopy.
AB  - Colonoscopy is a widespread diagnostic and therapeutic procedure. The most common
      complications include bleeding and perforation. Splenic rupture following
      colonoscopy is rarely encountered and is most likely secondary to traction on the
      splenocolic ligament. Exploratory laparotomy and splenectomy is the most commonly
      employed therapeutic intervention for this injury reported in the literature. We
      present the case of a patient with this potentially fatal complication who was
      treated successfully at our institution. To our knowledge it is the first report
      in the literature of laparoscopic splenectomy as a successful minimally invasive
      treatment of splenic rupture following colonoscopy. The patient was a 62-year-old
      female who underwent screening colonoscopy with polypectomies at the cecum,
      descending colon and rectum. Immediately following the procedure she developed
      abdominal pain and had a syncopal episode. Clinical, laboratory and imaging
      findings were suggestive of hemoperitoneum and a ruptured spleen. A diagnostic
      laparoscopy was emergently performed and revealed a grade IV splenic laceration
      and hemoperitoneum. Laparoscopic splenectomy was completed safely and
      effectively. The patient's postoperative recovery was uneventful. We conclude
      that splenic rupture after colonoscopy is a rare but dangerous complication. A
      high index of suspicion is required to recognize it early. Awareness of this
      potential complication can lead to optimal patient outcome. Laparoscopic
      splenectomy may be a feasible treatment option.

PMID- 23139654
TI  - Multiple ectopic hepatocellular carcinomas arising in the abdominal cavity.
AB  - Ectopic hepatocellular carcinoma (HCC) is a very rare clinical entity that is
      defined as HCC arising from extrahepatic liver tissue. This report presents a
      case of ectopic multiple HCC arising in the abdominal cavity. A 42-year-old
      otherwise healthy male presented with liver dysfunction at a general health
      checkup. Both HCV antibody and hepatitis B surface antigen were negative.
      Laboratory examination showed elevations in serum alpha-fetoprotein and PIVKA-II.
      Ultrasonography and computed tomography revealed multiple nodular lesions in the
      abdominal cavity with ascites without a possible primary tumor. Exploratory
      laparoscopy was performed, which revealed bloody ascites and multiple brown
      nodular tumors measuring approximately 10 mm in size that were disseminated on
      the perineum and mesentery. A postoperative PET-CT scan was performed but it did
      not reveal any evidence of a tumor in the liver. The tumors resected from the
      peritoneum were diagnosed as HCC. The present case of HCC was thought to have
      possibly developed from ectopic liver on the peritoneum or mesentery.

PMID- 23139655
TI  - Surgical procedure for sporadic colorectal cancer in patients with mild
      ulcerative colitis.
AB  - Restorative proctocolectomy is recognized as the standard procedure for colitic
      cancer in patients with ulcerative colitis (UC). However, whether this represents
      the optimal procedure for UC patients with sporadic cancer remains questionable,
      as functional quality of life differs substantially between patients with
      proctocolectomy and partial resection. This study considered possible problems
      associated with sporadic cancer in UC. Case 1 is a 55-year-old man with a 3-year
      history of UC who was treated with endoscopic resection for sporadic
      adenocarcinoma in the rectum. Low anterior resection was subsequently performed
      due to deep invasion. The final diagnosis was pT3. Differentiating between
      histopathological diagnoses of sporadic and colitic cancer was difficult. Case 2
      is a 71-year-old woman with a 6-year history of UC who was diagnosed with type 1
      sporadic sigmoid colon cancer. Dementia and umbilical hernia were present as
      complications. Total colectomy was performed in consideration of the coexisting
      complications. Although partial resection for sporadic cancer could be favorable
      in mild colitis, further immunosuppressive treatments have the potential to
      elevate the risk of recurrence for advanced cancer. Restorative proctocolectomy
      may be safer to avoid further recurrent colitis and cancer except in elderly
      patients or those with other complications.

PMID- 23139656
TI  - Tricuspid valve regurgitation as a presenting symptom of metastasized carcinoid
      tumor.
AB  - A 66-year-old woman was diagnosed with hepatic metastasized carcinoid tumor of
      the ileocecal junction resulting in elevated plasma chromogranin A levels and
      urinary 5-hydroxyindoleacetic acid (5-HIAA) levels. Further examination showed
      right-sided heart failure with severe tricuspid valve regurgitation. Carcinoid
      tumors produce serotonin which leads to flushing, secretory diarrhea,
      bronchospasm and hypotension, known as carcinoid syndrome. Serotonin is
      metabolized to 5-HIAA, which is inactive, in the liver and the lungs. However,
      hepatic metastases may result in direct exposure of the heart to serotonin, which
      induces plaque-like deformities on the tricuspid valve, and in turn induces valve
      regurgitation. This condition is known as carcinoid heart disease. Tricuspid
      valve regurgitation may induce risk of massive blood loss in case of liver
      surgery through high-volume backflow in the hepatic veins. This report shows the
      clinical relevance of carcinoid heart disease in the perioperative setting.

PMID- 23139657
TI  - Wireless Capsule Endoscopy Detects Meckel's Diverticulum in a Child with
      Unexplained Intestinal Blood Loss.
AB  - Meckel's diverticulum (MD) is the most common congenital anomaly of the
      gastrointestinal (GI) tract, affecting about 2% of the population. Most cases of
      Meckel's diverticula are asymptomatic. The diagnosis of symptomatic MD is often
      difficult to make. We report the case of an 8-year-old boy who presented with GI
      bleeding due to MD. The diagnostic difficulties after an initial negative
      endoscopic evaluation and the diagnostic value of the various endoscopic
      procedures are discussed. The patient had suffered from bright red stools for 20
      h before hospital admission. GI scintigraphy with (99m)Tc-Na-pertechnetate was
      negative for heterotopic gastric tissue in the small bowel area. Colonoscopy
      performed in order to exclude Crohn's disease was also negative. He was placed on
      ranitidine at a dose of 6 mg/kg body weight twice daily. The patient remained
      asymptomatic over a period of 6 months before he was readmitted due to
      macroscopic rectal bleeding. Upper endoscopy and colonoscopy used to investigate
      the source of bleeding showed normal macroscopic findings. Radiolabeling of blood
      constituents with (99m)Tc on delayed imaging showed radionucleotide concentration
      in the ascending and transverse colon suggestive of a lesion in the ileocecal
      area. Further investigation with the use of wireless capsule endoscopy revealed a
      MD. Wireless capsule endoscopy may thus be indicated for patients with GI blood
      loss when other diagnostic methods, such as upper and lower endoscopy and
      colonoscopy, have failed to identify the source of bleeding.

PMID- 23139658
TI  - Autologous fat transfer in a patient with lupus erythematosus profundus.
AB  - Lupus erythematosus profundus, a form of chronic cutaneous lupus erythematosus,
      is a rare inflammatory disease involving in the lower dermis and subcutaneous
      tissues. It primarily affects the head, proximal upper arms, trunk, thighs, and
      presents as firm nodules, 1 to 3 cm in diameter. The overlying skin often becomes
      attached to the subcutaneous nodules and is drawn inward to produce deep,
      saucerized depressions. We present a rare case of lupus erythematosus profundus
      treated with autologous fat transfer.

PMID- 23139659
TI  - Bullous Pemphigoid Accompanied by Aplastic Anemia: The Induction of IL-17
      Producing Cells in the Affected Areas of the Skin.
AB  - Th17 cells, characterized by IL-17 production, play a critical role in the
      pathogenesis of autoimmune diseases, including autoimmune bullous disorders and
      aplastic anemia (AA). In this report, we describe a 58-year-old Japanese man with
      bullous pemphigoid (BP) accompanied by AA. Interestingly, immunohistochemical
      staining revealed the existence of IL-17-producing cells in the skin biopsy
      specimens from BP. Our findings might suggest relationships between IL-17 and the
      pathogenesis of these autoimmune diseases, and, to our knowledge, this is the
      first English report of BP accompanied by AA.

PMID- 23139660
TI  - Profiles of tumor-infiltrating lymphocytes in a case of trichilemmal carcinoma
      with spontaneous regression.
AB  - We describe the case of a 69-year-old Japanese patient with spontaneous
      regression of trichilemmal carcinoma. We investigated the immunohistochemical
      profiles of tumor-infiltrating lymphocytes, focusing on cytotoxic granules,
      granulysin-bearing cells and immunosuppressive cells, such as regulatory T cells
      and tumor-associated macrophages. Our present study describes some of the
      possible mechanisms of the self-regression of cutaneous malignant tumors and
      potential therapies for trichilemmal carcinoma by modifying the tumor
      microenvironment.

PMID- 23139661
TI  - Image-Guided Radiation Therapy for Muscle-Invasive Carcinoma of the Urinary
      Bladder with Cone Beam CT Scan: Use of Individualized Internal Target Volumes for
      a Single Patient.
AB  - INTRODUCTION: While planning radiation therapy (RT) for a carcinoma of the
      urinary bladder (CaUB), the intra-fractional variation of the urinary bladder
      (UB) volume due to filling-up needs to be accounted for. This internal target
      volume (ITV) is obtained by adding internal margins (IM) to the contoured
      bladder. This study was planned to propose a method of acquiring individualized
      ITVs for each patient and to verify their reproducibility. METHODS: One patient
      with CaUB underwent simulation with the proposed 'bladder protocol'. After
      immobilization, a planning CT scan on empty bladder was done. He was then given
      300 ml of water to drink and the time (T) was noted. Planning CT scans were
      performed after 20 min (T+20), 30 min (T+30) and 40 min (T+40). The CT scan at
      T+20 was co-registered with the T+30 and T+40 scans. The bladder volumes at 20,
      30 and 40 min were then contoured as CTV20, CTV30 and CTV40 to obtain an
      individualized ITV for our patient. For daily treatment, he was instructed to
      drink water as above, and the time was noted; treatment was started after 20 min.
      Daily pre- and post-treatment cone beam CT (CBCT) scans were done. The bladder
      visualized on the pre-treatment CBCT scan was compared with CTV20 and on the post
      treatment CBCT scan with CTV30. RESULTS: In total, there were 65 CBCT scans (36
      pre- and 29 post-treatment). Individualized ITVs were found to be reproducible in
      93.85% of all instances and fell outside in 4 instances. CONCLUSIONS: The
      proposed bladder protocol can yield a reproducible estimation of the ITV during
      treatment; this can obviate the need for taking standard IMs.

PMID- 23139662
TI  - Hepatic artery chemoembolization for hepatocellular carcinoma recurrence confined
      to the transplanted liver.
AB  - BACKGROUND: Careful hepatocellular carcinoma (HCC) case selection permits
      orthotopic liver transplantation with the expectation of around 70% plus 5-year
      survival. However, many patients have tumor recurrences and there is little
      literature guidance in the management of these patients. AIMS: A retrospective
      examination of patients transplanted with HCC who subsequently developed liver
      recurrence. METHODS: A case cohort series of patients was prospectively followed
      who had liver-only multifocal tumor recurrence of HCC after liver transplant and
      were then treated with chemoembolization. RESULTS: All 6 patients had recurrent
      HCC. 2 had no response, 1 had stable disease, 2 had partial response (PR) and 1
      had complete disappearance (CR) of disease. Their survival (in months) was: 13
      (no response), 18 (no response), 12 (stable disease), 19 (PR), 30 (PR) and 50
      (CR). There were no liver toxicities. CONCLUSIONS: Chemoembolization for tumor
      recurrence in the transplanted liver is as safe as or safer than in the pre
      transplant liver, due to the absence of cirrhosis. In this series, there were 3
      of 6 responses with some long survivors.

PMID- 23139663
TI  - Cecal fibromatosis (desmoid tumor) mimicking periappendicular abscess: a case
      report.
AB  - A 32-year-old man presented to our department with abdominal pain and fever. In
      an earlier hospitalization he was diagnosed with periappendicular abscess and
      treated with antibiotics. Due to fever and 'non-resolution' of the abscess and
      due to its deep location in the lower abdomen, which excluded percutaneous
      drainage, we elected to operate the patient. A large mass in the cecum
      accompanied with an abscess resulted in a right hemicolectomy. The pathological
      examination revealed a desmoid tumor of the cecum. The patient's recovery was
      uneventful.

PMID- 23139664
TI  - Hepatitis B Virus Reactivation during Treatment with Multi-Tyrosine Kinase
      Inhibitor for Hepatocellular Carcinoma.
AB  - Hepatitis B virus (HBV) reactivation is well documented in individuals with
      cancer who receive certain cytotoxic or immunosuppressive therapies including
      rituximab treatment. As a general rule, the risk is greatest upon withdrawal of
      chemotherapy. The risk ranges from approximately 20 to 50% among HBsAg-positive
      carriers. A 67-year-old man was diagnosed with inoperable multiple hepatocellular
      carcinoma accompanied by an increase in alpha-fetoprotein and protein induced by
      vitamin K absence or antagonist II level. Eighteen weeks after starting on the
      oral multi-tyrosine kinase inhibitor TSU-68, laboratory investigations showed a
      substantial increase in serum transaminase levels (AST: 302 IU/l; ALT: 324 IU/l)
      and an elevation of the HBV-DNA level (6.9 log copies/ml). The diagnosis was that
      the cause of the acute hepatitis was HBV reactivation and we immediately
      administered entecavir. Two months after the initiation of daily entecavir
      treatment, laboratory findings showed that the serum levels of transaminases and
      ALP had improved (AST: 18 IU/l; ALT: 10 IU/l; ALP: 197 U/l). When the HBV markers
      were examined 4 months later, they were altered: HBeAg was negative and HBeAb was
      positive. Entecavir treatment was discontinued after 6 months. Although
      reactivation with rituximab has been reported, reactivation with a tyrosine
      kinase inhibitor is extremely unusual in a patient who is HBsAg negative but anti
      HBc positive. This is the first report describing HBV reactivation with an
      increasing HBV-DNA level in a HBsAg-negative/HBcAb-positive/HBsAb-positive
      patient who was treated with TSU-68 for hepatocellular carcinoma.

PMID- 23139665
TI  - Superficial Hyperthermia plus External Beam Radiation in the Palliation of
      Locally Progressive Chemoradiation-Resistant Breast Cancer.
AB  - Local chest wall progression of chemotherapy/radiation-resistant breast cancer
      can result in substantial morbidity. In this retrospective review of 39 patients
      in this difficult clinical setting treated at Cancer Treatment Centers of America
      (Eastern Regional Medical Center), approximately one-half of the population
      experienced meaningful short-term palliation and improvement in quality of life
      when managed with local superficial hyperthermia plus external beam radiation.

PMID- 23139666
TI  - Acute disseminated intravascular coagulation in neuroendocrine carcinoma.
AB  - Malignancy is a common cause of disseminated intravascular coagulation and
      usually presents as a chronic disorder in solid organ tumours. We present a rare
      case of recurrent acute disseminated intravascular coagulation in neuroendocrine
      carcinoma after manipulation, firstly, by core biopsy and, later, by cytotoxic
      therapy causing a release of procoagulants and cytokines from lysed tumour cells.
      This is reminiscent of tumour lysis syndrome where massive quantities of
      intracellular electrolytes and nucleic acid are released, causing acute metabolic
      imbalance and renal failure. This case highlights the potential complication of
      acute disseminated intravascular coagulation after trauma to malignant cells.

PMID- 23139667
TI  - Upfront Bevacizumab and Temozolomide or Fotemustine before Radiotherapy for
      Patients with Glioblastoma and Severe Neurological Impairment at Diagnosis.
AB  - Unresectable glioblastomas with severe neurological impairment at diagnosis have
      a poor prognosis. The conventional approach using a temozolomide-based
      chemoradiotherapy has limited efficiency on patients in the RTOG RPA V-VI
      classes. The activity of the antiangiogenic monoclonal antibody bevacizumab is
      well defined in recurrent glioblastoma, despite the fact that its impact on
      survival is not yet established. We wondered if neoadjuvant bevacizumab, used as
      upfront treatment in combination with a cytotoxic agent, was tolerable and active
      on neurological signs in patients with severe alteration of the neurological
      status due to the tumor being located in functional areas. Eight patients
      received intravenous bevacizumab, 10 mg/kg every 2 weeks, and either oral
      temozolomide (150-200 mg/m(2)/day for 5 days every 4 weeks) or intravenous
      fotemustine (80 mg/m(2) every 2 weeks). After an average of 5 cycles of
      bevacizumab, a clinical improvement of neurological functions was recorded in 8/8
      patients who could then receive radiotherapy at a conventional dose (60 Gy in 30
      fractions) with continuation of bevacizumab and the cytotoxic agent. Four out of
      the 8 patients benefited from a durable stabilization and experienced an
      unusually long survival in such a bad situation at diagnosis. In conclusion,
      neoadjuvant bevacizumab with chemotherapy appears to be feasible and efficient in
      a category of patients from the RTOG RPA V-VI classes, by allowing the completion
      of full-dose radiotherapy. A clinical trial is planned to confirm these
      retrospective observations.

PMID- 23139668
TI  - Primary small cell carcinoma of the tonsil: a case report and review of the
      literature.
AB  - Small cell cancer (SCC) of the tonsil is a rare and aggressive cancer. There are
      only 10 cases of tonsillar SCC reported in the English literature. We present a
      case of tonsillar SCC successfully treated with induction chemotherapy using
      carboplatin and etoposide followed by concurrent chemoradiation therapy with
      cisplatin as radiosensitizer. The patient remained free of recurrence after 3
      years of follow-up. We also provide a succinct review of all tonsillar SCC cases
      reported in the English literature and their outcomes.

PMID- 23139669
TI  - Circulating tumor cells as a potential biomarker in selecting patients for
      pulmonary metastasectomy from colorectal cancer: report of a case.
AB  - Pulmonary metastasectomy is indicated for selected patients with metastatic
      colorectal cancer. A 43-year-old woman presented with solitary pulmonary
      metastasis from descending colon cancer and pulmonary metastasectomy was
      performed because of absence of any other active metastasis as well as normal
      serum carcinoembryonic antigen value. However, she died due to early development
      of nodal and bone metastases within 6 months after thoracotomy. The presence of
      circulating tumor cells (CTCs) in the peripheral blood (6 CTCs/7.5 ml) was the
      only factor to predict such a poor prognosis, suggesting that the CTC test is
      useful in selecting patients for pulmonary metastasectomy.

PMID- 23139670
TI  - CBDCA + Pemetrexed + Bevacizumab and Its Maintenance Chemotherapy in a Case of
      Solitary Breast Metastasis from a Lung Adenocarcinoma Resistant to Gefitinib.
AB  - Based on the AVAPERL trial (36th ESMO 2011), CBDCA + pemetrexed + bevacizumab and
      its maintenance chemotherapy with pemetrexed + bevacizumab is a new promising
      regimen for the treatment of advanced non-small-cell lung adenocarcinoma. Herein,
      we report the rare case of a patient with solitary breast metastasis from a lung
      adenocarcinoma, which was effectively treated using CBDCA + pemetrexed +
      bevacizumab and its maintenance chemotherapy. A 57-year-old female was admitted
      to the hospital due to pleural effusion and cardiac tamponade caused by a lung
      adenocarcinoma possessing a mutation of the epidermal growth factor receptor
      (EGFR) gene (deletion of exon 19). The patient was treated by first-line
      chemotherapy (gefitinib 250 mg/body/day) which resulted in complete response.
      After 12 months, carcinoembryonic antigen was gradually increasing and she
      complained of a right breast mass. With a core-needle biopsy, the breast tumor
      was pathologically diagnosed as recurrence and solitary metastasis of a lung
      adenocarcinoma. Further study of the second mutation of EGFR revealed a T790M
      mutation. The patient was treated by second-line chemotherapy [CBDCA + pemetrexed
      + bevacizumab (AUC 6 + 500 mg/m(2) + 15 mg/kg)] and its maintenance chemotherapy
      (pemetrexed + bevacizumab). The cases of patients with breast metastasis from
      other organs are very rare. Immunohistopathological analysis is very useful to
      diagnose whether the malignancy is primary or not. In the case of a breast tumor
      with present or previous malignancy, a metastatic breast tumor should be
      considered. Furthermore, the biopsy of the breast metastasis also revealed the
      second mutation of resistance to gefitinib, T790M. Of note, according to our
      case, CBDCA + pemetrexed + bevacizumab and its maintenance chemotherapy is
      feasible and well tolerated for breast metastasis from a lung adenocarcinoma
      which is resistant to gefitinib and possesses the T790M mutation in the EGFR
      gene.

PMID- 23139672
TI  - Primary pure squamous cell carcinoma of the breast might be sensitive to
      Cisplatin-based chemotherapy.
AB  - Pure squamous cell carcinoma of the breast (PSCCB) is a rare condition. Surgery
      is usually the initial treatment. In some cases, complete excision of the tumor
      may be enough, while in other cases a mastectomy is required. In the literature,
      studies reported that PSCCB is an extremely aggressive disease associated with
      frequent locoregional and distant relapses and resultant death. Better therapy is
      therefore needed to improve patients' outcome. A literature review revealed that
      several patients with locoregional and distant metastasis were successfully
      treated using cisplatin-based regimens. I encountered a case of a patient with
      PSCCB who received neoadjuvant therapy using cytoxan, epirubicin, and
      fluorouracil without any response. Therefore, she underwent a mastectomy with
      lymph node dissection. Local recurrence occurred 3 weeks after surgery. She was
      started on taxotere and cisplatin. Four months after therapy, the recurrent
      tumors completely regressed. At this point, there is only circumstantial evidence
      that cisplatin-based regimens could be a promising option for the treatment of
      PSCCB. Clinical trials including large series of PSCCB are needed to increase our
      knowledge.

PMID- 23139671
TI  - WallFlexTM Duodenal Stent Placement in a Gastric Cancer Patient with Malignant
      Stenosis of a Roux-en-Y Gastrojejunostomy following Distal Gastrectomy.
AB  - A 69-year-old Japanese woman with a history of distal gastrectomy with a Roux-en
      Y reconstruction for advanced gastric cancer was admitted to our hospital
      complaining of severe dysphagia. On admission, the patient was only able to take
      liquids, and a firm, fist-sized tumor was palpable in her left upper abdomen. An
      endoscopic examination disclosed stenosis of the jejunal limb of the
      gastrojejunostomy. Abdominal computed tomography revealed that a recurrent tumor,
      5.0 cm in diameter, was compressing the jejunal limb of the gastrojejunostomy. A
      knitted nitinol self-expandable metallic stent (WallFlexTM duodenal stent) was
      placed endoscopically at the stenotic jejunum from the gastrojejunostomy. The
      time required for stenting and total endoscopic manipulation was 12 and 35
      minutes, respectively. No stent-related complications were observed. The patient
      could resume oral ingestion 1 day after endoscopic stenting and was discharged on
      the fifth day after treatment. She survived for 201 days after stenting. She
      continued oral ingestion for 194 days and stayed at home for 165 days. The
      WallFlex duodenal stent allows safe endoscopic stenting, even in cases of
      malignant stenosis of a gastrojejunostomy following distal gastrectomy. This
      stenting device will extend the indications for endoscopic palliation of gastric
      cancer patients with gastric outlet stenosis.

PMID- 23139673
TI  - Alterations of the cerebral white matter in a middle-aged patient with turner
      syndrome: an MRI study.
AB  - A 52-year-old woman with intellectual disability was admitted to the hospital due
      to pneumonia. MRI of her brain showed diffuse hyperintensities on T(2)-weighted
      and fluid attenuated inversion recovery images in the bilateral cerebral white
      matter. Laboratory examination revealed sustained high levels of serum KL-6.
      Karyotyping revealed partial monosomy of the X chromosome. This is the first case
      showing diffuse white matter lesions in the brain, and sustained high levels of
      serum KL-6 in Turner syndrome.

PMID- 23139674
TI  - Choroidal metastasis of adenocarcinoma of the lung presenting as pigmented
      choroidal tumor.
AB  - Our case represents a unique occurrence of pigmented choroidal tumor that
      clinically appeared as choroidal melanoma and was treated accordingly. At the
      same time, while evaluating the patient for systemic metastases of uveal
      melanoma, she was diagnosed as having lung carcinoma. Events that led to the
      enucleation of the eye enabled a histological diagnosis: pulmonary
      adenocarcinoma. In our case, it happened that a very rare pigmented choroidal
      metastatic tumor was the presenting sign of a pulmonary adenocarcinoma.

PMID- 23139675
TI  - Surgical management and scheimpflug analysis of an atypical lens coloboma.
AB  - A lens coloboma is not a true coloboma; it is just a zonular absence that causes
      a defect in the lens equator and hence a more spherical lens. It can be isolated
      or in association with iris, choroid or retinal colobomas. Typically the defect
      is present at the site of the embryonic fissure, but it can be present elsewhere.
      This congenital defect can cause amblyopia, especially when it is associated with
      cataract. We describe a case of a 39-year-old male with an atypical coloboma that
      was managed successfully with phacoemulsification, capsular tension ring and
      intraocular lens implantation. Scheimpflug image analysis and full
      ophthalmological assessment were performed. Scheimpflug images demonstrated a
      notching of the lens equator and an absence of zonulae. During the surgical
      procedure an ophthalmic viscosurgical device was used to tamponade the vitreous,
      and after continuous curvilinear capsulorhexis the capsular tension ring was
      inserted to allow the surgeon to perform a safe phacoemulsification.

PMID- 23139676
TI  - Central retinal artery occlusion and third cranial nerve palsy following nasal
      septoplasty.
AB  - BACKGROUND: Postoperative vision loss following routine nasal surgery is an
      extremely rare and devastating complication. We report a case of unilateral
      blindness due to central retinal artery occlusion associated with third cranial
      nerve following septoplasty. CASE REPORT: We report a patient who developed an
      unusual central retinal artery occlusion with unilateral blindness following
      nasal surgery under general anesthesia. A 45-year-old man underwent a nasal
      septal surgery for severe epistaxis. Soon after recovery, the patient noticed
      loss of vision in his right eye and was unable to lift his upper eyelid. Upon
      ophthalmic examinations, we determined that he had right-sided third cranial
      nerve palsy with central retinal artery obstruction and ptosis of right upper
      eyelid, restriction of ocular movements, and no perception of light in the right
      eye. Postoperative computerized tomography scan revealed multiple fractures of
      the left medial orbital wall, including one near the optic canal. Ptosis and
      ocular defects were recovered partially, but visual loss persisted until the last
      follow-up. CONCLUSION: This paper highlights one case of complete unilateral
      blindness from direct central retinal artery occlusion associated with third
      cranial nerve palsy following an apparently uneventful septorhinoplasty.
      Ophthalmologists and otolaryngologists should therefore be aware of the possible
      occurrence of such complications.

PMID- 23139677
TI  - Bilateral Multifocal Chorioretinitis and Optic Neuritis due to Epstein-Barr
      Virus: A Case Report.
AB  - Epstein-Barr virus (EBV) is a DNA virus that mainly causes infectious
      mononucleosis. Ocular manifestations are rare and typically mild. Only a few
      cases of EBV involving the retina or the optic nerve have been reported. Herein,
      we report the case of a 67-year-old man with bilateral chorioretinitis and optic
      neuritis due to EBV. The patient had no previous ocular history and presented
      with decreased vision in both eyes. His past medical history included EBV
      encephalopathy, which was confirmed serologically, a few months before.
      Ophthalmological examination revealed bilateral chorioretinitis and optic
      neuritis, confirmed by fluorescein angiography as well as electrophysiological
      tests (visual evoked potentials and electroretinogram). It is very important to
      include EBV in the differential diagnosis of chorioretinal atrophic lesions.
      Clinicians should be aware of ocular manifestations of EBV, in order to suggest
      ophthalmological examination and start treatment promptly before irreversible
      damage to the optic nerve or retina occurs.

PMID- 23139678
TI  - Branch retinal artery occlusion caused by toxoplasmosis in an adolescent.
AB  - PURPOSE: Branch retinal artery occlusion (BRAO), while not uncommon in elderly
      patient populations, is rare in children and adolescents. We report a case of a
      BRAO secondary to toxoplasmosis in this demographic. CASE: A previously healthy
      17-year-old male developed a unilateral BRAO in conjunction with inflammation and
      increased intraocular pressure. Family history was positive for cerebrovascular
      accidents in multiple family members at relatively young ages. The patient had a
      hypercoagulable workup as well as a cardiovascular workup which were both normal.
      A rheumatologic workup was unremarkable. By 3 weeks, a patch of retinitis was
      more easily distinguished from the BRAO and the diagnosis of ocular toxoplasmosis
      was made. Treatment was started with prednisone and azithromycin with subsequent
      improvement in vision. Toxoplasma antibody levels were elevated for IgG and
      negative for IgM, IgA, and IgE. The etiology of the BRAO was attributed to ocular
      toxoplasmosis. CONCLUSIONS: Vascular occlusions are rare in toxoplasmosis. This
      is the third case report of a BRAO in a patient in the pediatric population. The
      diagnosis of ocular toxoplasmosis should be considered in young patients with
      retinal artery occlusions associated with inflammation.

PMID- 23139679
TI  - Repeated treatment for macular edema in vein occlusion by intravitreal implant of
      dexamethasone.
AB  - BACKGROUND: Macular edema (ME) treatment has benefited from the recent
      intravitreal pharmacotherapy development of an intravitreal implant of
      dexamethasone (Ozurdex((r)), Allergan, Irvine, Calif., USA). However, its
      efficiency has never been illustrated beyond 3 injections. CASE PRESENTATION: We
      report the case of a 75-year-old woman with inferior branch vein occlusion, who,
      after laser photocoagulation treatment and recurrence after intravitreal
      injection of triamcinolone, benefited from 4 injections of Ozurdex. Her macular
      thickness and visual acuity (VA) progression were assessed for 17 months.
      CONCLUSIONS: This case report highlights the quick efficiency of Ozurdex on VA
      and ME with good reproducibility and tolerance, and without tachyphylaxis
      phenomenon. This is the first illustrated description of 4 consecutive injections
      for ME induced secondary to retinal vein occlusion.

PMID- 23139680
TI  - Spontaneous large serous retinal pigment epithelial tear.
AB  - PURPOSE: To report cases of spontaneous retinal pigment epithelial (RPE) tear
      complicating serous pigment epithelial detachment (PED). METHODS: The records of
      3 Asian patients with spontaneous giant RPE tear were reviewed retrospectively by
      including clinical presentation, angiography, optical coherence tomography,
      fundus autofluorescence imaging, and visual outcome. RESULTS: Three patients (4
      eyes) were included in this study, with a mean age of 48.3 (42-56) years, and a
      mean follow-up period of 7.75 (4-18) months. Fundus examination in all patients
      showed giant RPE tear associated with bullous PED. Two cases had a history of
      prior corticosteroid use, and 1 had no history of medication use. All 3 patients
      developed spontaneous resolution of subretinal fluid with no treatment. However,
      in patients who used corticosteroids, initial progression of the tear and
      subretinal fluid were observed despite ceasing medication. On subsequent follow
      up, an incomplete RPE regeneration was demonstrated by fundus autofluorescence
      imaging, and choroidal neovascularization developed in 1 patient. CONCLUSION:
      Large PED with RPE tear is a rare manifestation. When the fovea is spared, visual
      prognosis is favorable. No specific treatment is required, but careful choroidal
      neovascularization monitoring should be performed.

PMID- 23139681
TI  - Taste and temperature in swallowing transit time after stroke.
AB  - BACKGROUND: Oropharyngeal dysphagia is common in individuals after stroke. Taste
      and temperature are used in dysphagia rehabilitation. The influence of stimuli,
      such as taste and temperature, on swallowing biomechanics has been investigated
      in both healthy individuals and in individuals with neurological disease.
      However, some questions still remain unanswered, such as how the sequence of
      offered stimuli influences the pharyngeal response. The goal of the present study
      was to determine the influence of the sequence of stimuli, sour taste and cold
      temperature, on pharyngeal transit time during deglutition in individuals after
      stroke. METHODS: The study included 60 individuals with unilateral ischemic
      stroke, 29 males and 31 females, aged 41-88 years (mean age: 66.2 years) examined
      0-50 days after ictus (median: 6 days), with mild to moderate oropharyngeal
      dysphagia. Exclusion criteria were hemorrhagic stroke patients, patients with
      decreased level of consciousness, and clinically unstable patients, as confirmed
      by medical evaluation. The individuals were divided into two groups of 30
      individuals each. Group 1 received a nonrandomized sequence of stimuli (i.e.
      natural, cold, sour, and sour-cold) and group 2 received a randomized sequence of
      stimuli. A videofluoroscopic swallowing study was performed to analyze the
      pharyngeal transit time. Four different stimuli (natural, cold, sour, and sour
      cold) were offered. The images were digitalized and specific software was used to
      measure the pharyngeal transit time. Since the values did not present regular
      distribution and uniform variances, nonparametric tests were performed. RESULTS:
      Individuals in group 1 presented a significantly shorter pharyngeal transit time
      with the sour-cold stimulus than with the other stimuli. Individuals in group 2
      did not show a significant difference in pharyngeal transit time between stimuli.
      CONCLUSIONS: The results showed that the sequence of offered stimuli influences
      the pharyngeal transit time in a different way in individuals after stroke and
      suggest that, when the sour-cold stimulus is offered in a randomized sequence, it
      can influence the response to the other stimuli in stroke patients. Hence, the
      sour-cold stimulus could be used as a therapeutic aid in dysphagic stroke
      patients.

PMID- 23139682
TI  - Cerebral hemodynamic changes induced by a lumbar puncture in good-grade
      subarachnoid hemorrhage.
AB  - BACKGROUND: Patients with good-grade subarachnoid hemorrhage (SAH) are those
      without initial neurological deficit. However, they can die or present severe
      deficit due to secondary insult leading to brain ischemia. After SAH, in a known
      context of energy crisis, vasospasm, hydrocephalus and intracranial hypertension
      contribute to unfavorable outcome. Lumbar puncture (LP) is sometimes performed in
      an attempt to reduce intracranial pressure (ICP) and release headaches. We
      hypothesize that in good-grade SAH patients, a 20-ml LP releases headaches,
      reduces ICP and improves cerebral blood flow (CBF) as measured with O(15) PET
      scan. METHODS: Six good-grade (WFNS grade 1or 2) SAH patients (mean age 48 years,
      2 women, 4 men) were prospectively included. All aneurysms (4 anterior
      communicating artery and 2 right middle cerebral artery) were coiled at day 1.
      Patients were managed according to our local protocol. LP was performed for
      severe headache (VAS >7) despite maximal painkiller treatment. Patients were
      included when the LP was clinically needed. The 20-ml LP was done in the PET scan
      (mean delay between SAH and LP: 3.5 days). LP allows hydrostatic measurement of
      ICP. Arterial blood pressure (ABP) was noninvasively gauged with
      photoplethysmography. Every signal was monitored and analyzed off-line. Regional
      CBF (rCBF) was measured semiquantitatively with O(15) PET before and after LP.
      Then we calculated the difference between baseline and post-LP condition for each
      area: positive value means augmentation of rCBF after the LP, negative value
      means reduction of rCBF. Individual descriptive analysis of CBF was first
      performed for each patient; then a statistical group analysis was done with SPM
      for all voxels using t statistics converted to Z scores (p < 0.01, Z score >3.2).
      RESULTS: A 20-ml LP yielded a reduction in pain (-4), a drop in ICP (24.3 +/-
      12.5 to 6.9 +/- 4.7 mm Hg), but no change in ABP. Descriptive and statistical
      image analysis showed a heterogeneous and biphasic change in cerebral
      hemodynamics: rCBF was not kept constant and either augmented or decreased after
      the drop in ICP. Hence, cerebrovascular reactivity was spatially heterogeneous
      within the brain. rCBF seems to augment in the brain region roughly close to the
      bleed and to be reduced in the rest of the brain, with a rough plane of symmetry.
      CONCLUSIONS: In good-grade SAH, LP releases headaches and lowers ICP. LP and the
      drop in ICP have a heterogeneous and biphasic effect on rCBF, suggesting that
      cerebrovascular reactivity is not spatially homogeneous within the brain.

PMID- 23139683
TI  - Characteristics of intracranial aneurysms in the else kroner-fresenius registry
      of autosomal dominant polycystic kidney disease.
AB  - BACKGROUND: Patients who harbor intracranial aneurysms (IAs) run a risk for
      aneurysm rupture and subsequent subarachnoid hemorrhage which frequently results
      in permanent deficits or death. Prophylactic treatment of unruptured aneurysms is
      possible and recommended depending on the size and location of the aneurysm as
      well as patient age and condition. IAs are major manifestations of autosomal
      dominant polycystic kidney disease (ADPKD). Current guidelines do not suggest
      surveillance of IAs in ADPKD except in the setting of family history if IA was
      known in any relative with ADPKD. Management of IAs in ADPKD is problematic
      because limited data exist from large studies. METHODS: We established the Else
      Kroner-Fresenius Registry for ADPKD in Germany. Clinical data were assessed for
      age at diagnosis of IAs, stage of renal insufficiency, and number, location and
      size of IAs as well as family history of cerebral events. Patients with
      symptomatic or asymptomatic IAs were included. All patients with ADPKD-related
      IAs were offered mutation scanning of the susceptibility genes for ADPKD, the
      PKD1 and PKD2 genes. RESULTS: Of 463 eligible ADPKD patients from the population
      base of Germany, 32 (7%) were found to have IAs, diagnosed at the age of 2-71
      years, 19 females and 13 males. Twenty (63%) of these 32 patients were
      symptomatic, whereas IAs were detected in an asymptomatic stage in 12 patients.
      IAs were multifocal in 12 and unifocal in 20 patients. In 26 patients (81%), IAs
      were diagnosed before end-stage renal failure. Twenty-five out of 27 unrelated
      index cases (93%) had no IAs or cerebral events documented in their relatives
      with ADPKD. In 16 unrelated index patients and 3 relatives, we detected germline
      mutations. The mutations were randomly distributed across the PKD1 gene in 14 and
      the PKD2 gene in 2 index cases. Questionnaires answered for 320/441 ADPKD
      patients without IAs revealed that only 45/320 (14%) had MR angiography.
      CONCLUSION: In ADPKD, rupture of IAs occurs frequently before the start of
      dialysis, is only infrequently associated with a family history of IAs or
      subarachnoid hemorrhage, and is associated with mutations either of the PKD1 or
      the PKD2 gene of any type. Screening for IAs is widely insufficiently performed,
      should not be restricted to families with a history of cerebral events and should
      be started before end-stage renal failure.

PMID- 23139684
TI  - Insular ischemic stroke: clinical presentation and outcome.
AB  - BACKGROUND: The insula is a small but complex structure located in the depth of
      the sylvian fissure, covered by the frontal, parietal and temporal operculum.
      Ischemic strokes limited to the insula are rare and have not been well studied.
      Our objective is to better define the clinical presentation and outcome of
      insular ischemic strokes (IIS). METHODS: We reviewed the institutional
      prospective, consecutive stroke database from two centers to identify patients
      with IIS seen between 2008 and 2010. We also searched the Medline database using
      the keywords insula(r), infarction and stroke to identify previously published
      IIS cases confirmed by MRI. Minimal extension to an adjacent operculum or
      subinsular area was accepted. Clinicoradiological correlation was performed by
      distinguishing IIS involving the anterior (AIC) or posterior insular cortex
      (PIC). We collected clinical, demographic and radiological data. The outcome was
      determined using the modified Rankin Scale (mRS). RESULTS: We identified 7
      patients from our institutions and 16 previously published cases of IIS. Infarcts
      were limited to the AIC (n = 4) or the PIC (n = 12) or affected both (n = 7). The
      five most frequent symptoms were somatosensory deficits (n = 10), aphasia (n =
      10), dysarthria (n = 10), a vestibular-like syndrome (n = 8) and motor deficits
      (n = 6). A significant correlation was found between involvement of the PIC and
      somatosensory manifestations (p = 0.04). No other statistically significant
      associations were found. IIS presentation resembled a partial anterior
      circulation infarct (n = 9), a lacunar infarct (n = 2) or a posterior circulation
      infarct (n = 2). However, most cases presented findings that did not fit with
      these classical patterns (n = 10). At the 6 month follow up, mRS was 0 in 8/23
      (35%) patients, 1-2 in 7/23 (30%) and unknown in 8/23 (35%). CONCLUSIONS: IIS
      presentation is variable. Due to the confluence of functions in a restricted
      region, it results in multimodal deficits. It should be suspected when vestibular
      like or motor but especially somatosensory, speech or language disturbances are
      combined in the same patient. The outcome of IIS is often favorable. Larger
      prospective studies are needed to better define the clinical presentation and
      outcome of IIS.

PMID- 23139685
TI  - Alzheimer's disease with vascular component: a distinct clinical entity?
AB  - BACKGROUND: Longitudinal reports on the clinical features of patients with
      Alzheimer's disease (AD) and concomitant cerebrovascular disease are scarce.
      METHODS: We elaborated a working definition of AD with vascular component (ADVC),
      and this definition was retrospectively investigated in a cohort of patients with
      cognitive deterioration who were prescribed a cholinesterase inhibitor during
      usual practice. RESULTS: A total of 137 patients with probable AD and 66 patients
      with ADVC were studied during a mean follow-up period of 2.8 years. Univariate
      analyses demonstrated worse functional evolution and anticipation of psychotic
      symptoms and agitation in the ADVC group. CONCLUSIONS: The present results are
      consistent with an additive model of predominantly frontal-subcortical vascular
      damage in AD.

PMID- 23139686
TI  - The complex picture test in dementia.
AB  - The newly developed Complex Picture Test (CPT) examines main cognitive domains,
      especially perceptual and visual-spatial abilities. The potential usefulness of
      the CPT in the assessment of dementia was evaluated. Patients with different
      forms of dementia [14 vascular dementia (VaD), 30 Alzheimer's disease (AD), 6
      Parkinson's disease dementia (PDD)], 12 subjects with mild cognitive impairment
      (MCI), and 30 matched controls were examined by the CPT, Mini-Mental State
      Examination (MMSE), the WAIS-R Digit Span subtest, and the Clock Drawing Test
      (CDT). The CPT consists of 10 complex pictures, each presenting characteristics
      paradoxically in opposition to each other. The subjects scored points for naming
      the object and noticing the paradox. One point was added for commenting on the
      paradox without prompting (3 points each picture/maximum of 30). CPT scores were
      significantly higher in the control group (mean +/- SD, 29.46 +/- 1.43) than in
      the AD, VaD, MCI, and PDD groups (13.1 +/- 2.3, 16.9 +/- 3.5, 23.2 +/- 1.4, and
      23.6 +/- 3.4, respectively; p < 0.05). Significant positive correlations between
      MMSE, Digit Span, CDT, and CPT scores were observed (rho 0.76, 0.35, and 0.56,
      respectively). These data show perception of complex pictures being compromised
      in dementia. The correlation between CPT scores and MMSE scores suggests that
      tests may be used as a brief screening tool for dementia.

PMID- 23139687
TI  - Compliance and Caregiver Satisfaction in Alzheimer's Disease: Results from the
      AXEPT Study.
AB  - BACKGROUND/AIMS: According to experimental data, a transdermal application is
      preferred by caregivers of Alzheimer's disease (AD) patients compared with oral
      medications. The AXEPT study compared compliance to treatment among community
      dwelling patients with mild-to-moderate AD treated with transdermal application
      compared to oral medications and caregiver satisfaction in a real clinical
      setting. METHODS: Data from 45 memory clinics in Italy were collected between
      September 8, 2010 and January 31, 2011. Compliance to treatment and caregiver
      satisfaction were measured using the Caregiver Medication Interview. RESULTS: A
      total of 855 AD patients and their caregivers participated in the study. Nearly
      80% of caregivers of patients on patch were not concerned about adherence to
      treatment compared with 64% of caregivers of patients on oral drugs. Among
      caregivers of patients on patch, 94% did not report any difficulties in
      remembering to administer treatment compared with 73% of caregivers of patients
      on oral medications. The highest level of compliance and satisfaction was
      reported by caregivers of patients on transdermal application. CONCLUSION:
      Caregivers of patients treated with a transdermal application appeared to be more
      satisfied and reported a higher level of compliance than caregivers of patients
      receiving anti-AD oral medications.

PMID- 23139688
TI  - The Lay Public's Understanding and Perception of Dementia in a Developed Asian
      Nation.
AB  - BACKGROUND: Early detection of dementia aims to improve treatment outcomes.
      However, poor perception and understanding of dementia are significant barriers.
      We aim to investigate the public's perception of dementia and identify variables
      associated with the different profiles of public perception. METHODS: A custom
      designed questionnaire was used to assess laypersons' knowledge and perception of
      dementia during a health fair at a public hospital in Singapore, a developed
      Asian nation. Out of a sample of 370 subjects, 32 declined to participate
      (response rate = 91.4%). Latent class analysis (LCA) was used to identify
      meaningful subgroups of subjects from significant associations with multiple
      indicators of dementia awareness. Multinomial logistic regression was performed
      exploring variables associated with each of the subgroups derived from LCA.
      RESULTS: The majority of the study participants were female (66.9%), 65 years or
      older (71.1%), and ethnic Chinese (88.1%). LCA classified the study participants
      into 3 subgroups: Class 1 (good knowledge, good attitude), Class 2 (good
      knowledge, poor attitude), and Class 3 (poor knowledge, poor attitude), in
      proportions of 14.28, 63.83, and 21.88%, respectively. Compared to other classes,
      participants with good knowledge and good attitude towards dementia (Class 1)
      were more likely to know someone with dementia and understand the effects of the
      disease, be married, live in private housing, receive higher monthly income, and
      not profess belief in Buddhism, Taoism, or Hinduism. CONCLUSION: Our results show
      that the public in Singapore may not be ready for screening initiatives and early
      dementia diagnosis. Education efforts should be targeted at lower socioeconomic
      groups, singles, and those of certain oriental religions.

PMID- 23139689
TI  - Risk factors for renal failure in patients with lupus nephritis: data from the
      spanish registry of glomerulonephritis.
AB  - BACKGROUND: Lupus nephritis (LN) is a severe complication of systemic lupus
      erythematosus. Data from national registries based on renal biopsies are scarce.
      The aim of our study was to analyze the demographic characteristics,
      clinicopathological correlations, and risk factors associated with renal failure
      in patients with LN at the time of renal biopsy. METHODS: We performed a cross
      sectional observational study based on data from the Spanish Registry of
      Glomerulonephritis for the years 1994-2009. The outcome measure was the presence
      of renal failure (eGFR <60 ml/min/1.73 m(2)). We also recorded age, gender,
      proteinuria levels, hypertension, and histological class. RESULTS: We collected
      17,525 native renal biopsies, of which 1,648 biopsies showed LN lesions. In
      total, 609 patients (37%) showed renal failure at the time of renal biopsy. The
      univariate analysis showed that these patients were older, had higher levels of
      proteinuria, and a higher prevalence of hypertension than the group with eGFR
      >=60 ml/min/ 1.73 m(2). The histological class of LN was recorded for 566
      patients, and multivariate logistic regression analysis showed that the
      independent risk factors for renal failure at the time of renal biopsy were age
      (OR 1.03; 95% CI 1.01-1.04), male gender (OR 1.94; 95% CI 1.12-3.10),
      hypertension (OR 3.18; 95% CI 2.16-4.67), proteinuria (OR 1.15; 95% CI 1.08
      1.24), and histological classes III and IV (OR 1.82; 95% CI 1.16-2.87).
      CONCLUSIONS: Data from the Spanish Registry of Glomerulonephritis provide
      valuable information about risk factors for renal failure in patients with LN at
      the time of renal biopsy.

PMID- 23139690
TI  - Visual memory of meaningless shapes in children and adolescents with autism
      spectrum disorders.
AB  - OBJECTIVE: Visual memory is an important cognitive ability, which has been
      studied in individuals with Autism Spectrum Disorders (ASDs). In such studies
      meaningful shapes were used more frequently. Since meaningless shapes provide a
      better assessment of short term visual memory, in this study we used them to
      evaluate visual memory in children and adolescents with ASDs compared to the
      normal group. METHODS: Four visual memory tests of Cambridge Neuropsychological
      Test Automated Battery (CANTAB) including Paired Associates Learning (PAL),
      Pattern Recognition Memory (PRM), Spatial Recognition Memory (SRM) and Delayed
      Matching to Sample (DMS) were administered to 15 children and adolescents with
      ASDs (high functioning autism and Asperger syndrome) and to 15 normal
      participants aged 8 to 17,with IQ of above 70. RESULTS: Individuals with ASDs
      performed worse than the normal group on visual memory tasks. After eliminating
      IQ as a covariate, no significant difference was observed between the two groups
      in terms of visual memory performance. CONCLUSION: It seems that deficits on
      visual memory tasks in youths with ASDs could be related to their general
      intellectual abilities.

PMID- 23139691
TI  - Birth order and sibling gender ratio of a clinical sample of children and
      adolescents diagnosed with attention deficit hyperactivity disorder.
AB  - OBJECTIVE: It is not clear whether sibling's gender ratio is associated with
      attention deficit hyperactivity disorder (ADHD). This study examines whether
      inattentiveness severity and hyperactivity/impulsivity severity are associated
      with birth order of children with ADHD. METHOD: Participants are a clinical
      sample of 173 children and adolescents with ADHD and 43 ones without ADHD.
      Diagnoses were made using Diagnostic and Statistical Manual of Mental Disorders
      forth edition-Text Revision (DSM-IV-TR), diagnostic criteria according to face-to
      face interview with the children and their parents. ADHD DSM-IV checklist was
      used to measure inattentiveness and hyperactivity/impulsivity scores. RESULTS:
      The association of birth order and diagnosis of ADHD was not statistically
      significant after adjusting for covariate factors. The gender ratio of siblings
      is not associated with ADHD. CONCLUSION: Birth order and siblings gender ratio
      are independent of ADHD diagnosis. The results of this study support the fact
      that genetic factors rather than environmental factor of birth order is
      associated with ADHD. Moreover, contrary to autism, the current results do not
      suggest the androgen theory for ADHD.

PMID- 23139692
TI  - Dietary intake, growth and development of children with ADHD in a randomized
      clinical trial of Ritalin and Melatonin co-administration: Through circadian
      cycle modification or appetite enhancement?
AB  - OBJECTIVE: It is postulated that ritalin may adversely affect sleep, appetite,
      weight and growth of some children with ADHD. Therefore, we aimed to evaluate
      melatonin supplementation effects on dietary intake, growth and development of
      children with ADHD treated with ritalin through circadian cycle modification and
      appetite mechanisms. METHOD: After obtaining consent from parents, 50 children
      aged 7-12 with combined form of AD/HD were randomly divided into two groups based
      on gender blocks: one received melatonin (3 or 6 mg based on weight) combined
      with ritalin (1mg/kg) and the other took placebo combined with ritalin (1mg/kg)
      in a double blind randomized clinical trial. Three-day food record, and standard
      weight and height of children were evaluated prior to the treatment and 8 weeks
      after the treatment. Children's appetite and sleep were evaluated in weeks 0, 2,
      4 and 8. Hypotheses were then analyzed using SPSS17. RESULTS: Paired sample t
      test showed significant changes in sleep latency (23.15+/-15.25 vs. 17.96+/
      11.66; p=0.047) and total sleep disturbance score (48.84+/-13.42 vs. 41.30+/
      9.67; p=0.000) before and after melatonin administration, respectively. However,
      appetite and food intake did not change significantly during the study. Sleep
      duration and appetite were significantly correlated in melatonin group (Pearson
      r=0.971, p=0.029). Mean height (138.28+/-16.24 vs. 141.35+/-16.78; P=0.000) and
      weight (36.73+/-17.82 vs. 38.97+/-17.93; P=0.005) were significantly increased in
      melatonin treated children before and after the trial. CONCLUSION: Administration
      of melatonin along with ritalin improves height and weight growth of children.
      These effects may be attributed to circadian cycle modification, increasing sleep
      duration and the consequent more growth hormone release during sleep.

PMID- 23139693
TI  - Marital Satisfaction amongst Parents of Children with Attention Deficit
      Hyperactivity Disorder and Normal Children.
AB  - OBJECTIVE: The aim of this study was to compare marital satisfaction between
      parents of children with attention deficit hyper activity disorder (ADHD) and
      parents of normal children. METHOD: In this study we have selected 400 parents
      (200 parents of children with ADHD and 200 parents of normal children), whose
      children age range was 6-18 years. Data were collected using Enrich marital
      satisfaction Questionnaire, Kiddie Schedule for Affective Disorders and
      Schizophrenia Present and Lifetime Version (K-SADS-PL) and Conner's Questionnaire
      (parent and self-report forms). For data analysis, SPSS software17, bivariate
      Chi(2)- test, and independent t- test were used. RESULTS: The mean of marital
      satisfaction in parents of normal children was higher than parents of ADHD
      children. In the bivariate Chi(2)- test, the p value was less than 0.05, and the
      obtained t was more than the table-t (1.96), so it can be assumed that there is a
      significant difference between parents of normal children and those with ADHD
      children in their marital satisfaction. The level of marital satisfaction
      (strongly agree level) was 2.8% lower among parents of ADHD children compared to
      parents of normal children. CONCLUSION: Findings indicate that parents with ADHD
      children have lower level of marital satisfaction than parents with normal
      children.

PMID- 23139694
TI  - Social competence and behavior problems in preschool children.
AB  - OBJECTIVE: This study examines development of social competence, and behavior
      problems in kindergarten children during a specific period of childhood. METHOD:
      A sample of 499 kindergarten children (244 girls and 255 boys) with the age range
      of 2 years up to 5 years and 6 months was selected using the random stratified
      sampling method. To collect data, California Preschool Social Competence Scale
      and Social Skills Rating System were completed by kindergarten teachers. RESULTS:
      The trend analysis shows that both the linear and quadratic trends for verbal
      facility were statistically significant. Similarly, both the linear and cubic
      trends were significant for considerateness, and the linear trend tendency was
      significant for subscales of extraversion, response to unfamiliar and task
      orientation. Pearson's correlation coefficient yielded a low-to-moderate and
      negative correlation patterns between social component and problem behaviors.
      CONCLUSION: The study findings indicate a significant linear trend between the
      progression in social competence and increasing age, consequently leading to a
      decrease in social problems for children whose age was from 2 years up to 5 years
      and 6 months.

PMID- 23139695
TI  - Persian translation of perception of psychiatry survey questionnaire and
      evaluation of its psychometric properties.
AB  - OBJECTIVE: Test the psychometric properties of the Persian version of the
      Perception of Psychiatry Survey questionnaire, which is being used in a large
      multi-site international study, of which we were part. This instrument was
      designed to measure the attitudes of medical educators to psychiatry. METHOD: We
      used World Health Organization guideline as the methodological model for Persian
      translation. The Persian version of Perception of Psychiatry Survey questionnaire
      was administered to a convenience sample of 100 medical teachers at Tehran
      University of Medical Sciences and Azad University. The content validity,
      internal consistency, and test-retest reliability of the instrument were
      assessed. RESULTS: No item changed completely during the process of translation
      and cultural adaptation. The content validity of translation and back translation
      was 0.74 and 0.86 according to Feliss Kappa Statistic. The Cronbach's alpha
      coefficient was 0.76 for the Persian version and for its subdivisions ranged from
      0.59 to 0.81. The inter class correlation (ICC) coefficient for test-retest
      reliability of the whole instrument was 0.89. CONCLUSION: The Persian version of
      Perception of Psychiatry Survey questionnaire could be considered as a good cross
      cultural equivalent for original English version. The instrument is a reliable
      instrument in terms of internal consistency and test-retest reliability.

PMID- 23139696
TI  - The Relationship between Obsessions and Compulsions and Negative and Positive
      Symptoms in Schizophrenia.
AB  - OBJECTIVE: The aim of the present study is to investigate the relationship
      between obsessive-compulsive symptoms (OCSs) and negative and positive symptoms
      in schizophrenia. METHODS: Subjects of the study comprised of 31 schizophrenia
      with obsessive-compulsive symptoms (19 men and 12 women) selected by convenience
      sampling method from Iran psychiatric Hospital. The diagnoses were established on
      the basis of DSM-IV-TR. The required data were obtained using Positive and
      Negative Syndrome Scale (PANSS) and Yale-Brown Obsessive-Compulsive scale (Y
      BOC). RESULTS: The results of multiple regression analysis indicated that
      obsessive symptoms inversely predict negative symptoms. In other words, as the
      obsessive symptoms increase, the negative symptoms of schizophrenia decrease.
      Nevertheless, no significant relationship was found between OCSs and positive
      symptoms. CONCLUSION: This study reveals that OCSs exert a protective effect on
      schizophrenia and do not necessarily cause poorer prognosis.

PMID- 23139697
TI  - Olanzapine as a cause of urinary incontinence: a case report.
AB  - Olanzapine, an atypical antipsychotic, is one of the most commonly used
      antipsychotics. Though olanzapine is commonly associated with endocrine side
      effects, it is generally well tolerated by most patients and is rarely associated
      with urinary incontinence. This report highlights the case of a 23 -year old male
      patient with schizophrenia who developed severe urinary incontinence following
      the use of olanzapine. No medications were given to relieve the incontinence
      contrary to some other studies where ephedrine was used. Olanzapine was changed
      to trifluoperazine, and the patient's condition improved within two days. Urinary
      incontinence, though uncommon, is an embarrassing side effect of olanzapine which
      could negatively affect drug compliance. As such, clinicians should enquire about
      it in order to improve the patient's health.

PMID- 23139698
TI  - Effects of Membrane Rheology on Leuko-polymersome Adhesion to Inflammatory
      Ligands.
AB  - A strategy for treating inflammatory disease is to create micro-particles with
      the adhesive properties of leukocytes. The underlying rheology of deformable
      adhesive microspheres would be an important factor in the adhesive performance of
      such particles. In this work the effect of particle deformability on the selectin
      mediated rolling of polymer vesicles (polymersomes) is evaluated. The rheology of
      the polymersome membrane was modulated by cross-linking unsaturated side-chains
      within the hydrophobic core of the membrane. Increased membrane rigidity resulted
      in decreased rates of particle recruitment rather than decreased average rolling
      velocities. Reflective interference contrast microscopy of rolling vesicles
      confirmed that neither flaccid nor rigid vesicles sustained close contacts with
      the substrate during rolling adhesion. A variable-shear rate parallel-plate flow
      chamber was employed to evaluate individual vesicles rolling on substrates under
      different flow conditions. Analysis of the trajectories of single flaccid
      vesicles revealed several distinct populations of rolling vesicles; however, some
      of these populations disappear when the vesicle membranes are made rigid. This
      work shows that membrane mechanics affects the capture, but not the rolling
      dynamics, of adherent leuko-polymersomes.

PMID- 23139699
TI  - Self-assembly of 2D membranes from mixtures of hard rods and depleting
      polymers().
AB  - We combine simulations and experiments to elucidate the molecular forces leading
      to the assembly of two dimensional membrane-like structures composed of a one rod
      length thick monolayer of aligned rods from an immiscible suspension of hard rods
      and depleting polymers. Computer simulations predict that monolayer membranes are
      thermodynamically stable above a critical rod aspect ratio and below a critical
      depletion interaction length scale. Outside of these conditions alternative
      structures such as stacked smectic columns or nematic droplets are
      thermodynamically stable. These predictions are confirmed by subsequent
      experiments using a model system of virus rod-like molecules and non-adsorbing
      polymer. Our work demonstrates that collective molecular protrusion fluctuations
      alone are sufficient to stabilize membranes composed of homogenous rods with
      simple excluded volume interactions.

PMID- 23139700
TI  - Microfluidic systems for single DNA dynamics.
AB  - Recent advances in microfluidics have enabled the molecular-level study of
      polymer dynamics using single DNA chains. Single polymer studies based on
      fluorescence microscopy allow for the direct observation of non-equilibrium
      polymer conformations and dynamical phenomena such as diffusion, relaxation, and
      molecular stretching pathways in flow. Microfluidic devices have enabled the
      precise control of model flow fields to study the non-equilibrium dynamics of
      soft materials, with device geometries including curved channels, cross-slots,
      and microfabricated obstacles and structures. This review explores recent
      microfluidic systems that have advanced the study of single polymer dynamics,
      while identifying new directions in the field that will further elucidate the
      relationship between polymer microstructure and bulk rheological properties.

PMID- 23139701
TI  - Effects of an Early Family Intervention on Children's Memory: The Mediating
      Effects of Cortisol Levels.
AB  - Developmental psychologists have long been concerned with the ways that early
      adversity influences children's long-term outcomes. In the current study,
      activity of the HPA axis of medically at-risk (e.g., preterm) infants was
      measured as a result of maternal participation in a novel cognitively-based home
      visitation program (versus a Healthy Start home visitation program). Maternal
      participation in the cognitive intervention predicted lower basal cortisol levels
      among infants - with reduced levels of maternal avoidance/withdrawal serving as a
      mediator of this relation. Lower cortisol levels in infancy, in turn, predicted
      higher verbal short-term memory at age 3. Short-term memory represents a
      cognitive ability that has importance for children's later educational outcomes.
      Findings provide experimental evidence concerning the pathway by which an early
      intervention may produce hormonal changes that can, in turn, influence children's
      learning outcomes.

PMID- 23139702
TI  - Rituximab combination therapy in relapsing multiple sclerosis.
AB  - In multiple sclerosis (MS), the presence of B cells, plasma cells and excess
      immunoglobulins in central nervous system lesions and in the cerebrospinal fluid
      implicate the humoral immune system in disease pathogenesis. However, until the
      advent of specific B-cell-depleting therapies, the critical role of B cells and
      their products in MS was unproven. Rituximab, a monoclonal antibody that depletes
      B cells by targeting the CD20 molecule, has been shown to effectively reduce
      disease activity in patients with relapsing MS as a single agent. Our
      investigator-initiated phase II study is the only published clinical trial in
      which rituximab was used as an add-on therapy in patients with relapsing MS who
      had an inadequate response to standard injectable disease-modifying therapies
      (DMTs). The primary endpoint, magnetic resonance imaging (MRI) gadolinium
      enhanced (GdE) lesion number before versus after rituximab, showed significant
      benefit of rituximab (74% of post-treatment MRI scans being free of GdE lesions
      compared with 26% free of GdE lesions at baseline; p < 0.0001). No differences
      were noted comparing patients on different DMTs. Several secondary clinical
      endpoints, safety and laboratory measurements (including B- and T-cell numbers in
      the blood and cerebrospinal fluid (CSF), serum and CSF chemokine levels,
      antibodies to myelin proteins) were assessed. Surprisingly, the decline in B-cell
      number was accompanied by a significant reduction in the number of T cells in
      both the peripheral blood and CSF. Rituximab therapy was associated with a
      significant decline of two lymphoid chemokines, CXCL13 and CCL19. No significant
      changes were observed in serum antibody levels against myelin proteins [myelin
      basic protein (MBP) and myelin/oligodendrocyte glycoprotein (MOG)] after
      treatment. These results suggest that B cells play a role in MS independent from
      antibody production and possibly related to their role in antigen presentation to
      T cells or to their chemokine/cytokine production.

PMID- 23139703
TI  - Psychotic illness in patients with epilepsy.
AB  - Apart from the rather rare ictal psychotic events, such as non-convulsive status
      epilepticus, modern epileptic psychoses have been categorized into three main
      types; chronic and acute interictal psychoses (IIPs) and postictal psychosis
      (PIP). Together, they comprise 95% of psychoses in patients with epilepsy (PWE).
      Four major questions, that is, "Is psychosis in PWE a direct consequence of
      epilepsy or schizophrenia induced by epilepsy?", "Is psychosis in PWE homogeneous
      or heterogeneous?", "Does psychosis in PWE have symptomatological differences
      from schizophrenia and related disorders?", "Is psychosis in PWE uniquely
      associated with temporal lobe epilepsy (TLE)?" are tried to be answered in this
      review with relevant case presentations. In the final section, we propose a
      tentative classification of psychotic illness in PWE, with special attention to
      those who have undergone epilepsy surgery. Psychotic disorders in PWE are often
      overlooked, mistreated, and consequently lingering on needlessly. While early
      diagnosis is unanimously supported as a first step to avoid this delay, necessity
      of switching from antiepileptic drugs with supposedly adverse psychotopic
      effects. to others is more controversial. To elucidate the riddle of alternative
      psychosis, we need badly further reliable data.

PMID- 23139705
TI  - Assessment scales in dementia.
AB  - Dementia involves progressive and often remorseless decline in cognition,
      function, behaviour and care needs. Assessment in dementia relies on collateral
      as well as patient-derived information. Many assessment scales have been
      developed over decades for use in dementia research and care. These scales are
      used to reduce uncertainty in decision making, for example in screening for
      cognitive impairment, making diagnoses of dementia and monitoring change. Ideal
      scales used in dementia should demonstrate face validity and concurrent validity
      against gold standard assessments, should be reliable, practical, and should rely
      on objective rather than subjective information. Assessment scales in the domains
      of cognition, function, behaviour, quality of life, depression in dementia, carer
      burden and overall dementia severity are reviewed in this article. The practical
      use of these scales in clinical practice and in research is discussed.

PMID- 23139704
TI  - Neurochemical biomarkers in Alzheimer's disease and related disorders.
AB  - Neurochemical biomarkers for diagnosing dementias are currently under intensive
      investigation and the field is rapidly expanding. The main protagonists and the
      best defined among them are cerebrospinal fluid levels of Abeta42, tau and its
      phosphorylated forms (p-tau). In addition, novel cerebrospinal fluid biomarkers
      are emerging and their multiparametric assessment seems most promising for
      increasing the accuracy in neurochemical dementia diagnostics. The combined
      assessment of Abeta42 and p-tau has recently shown value for diagnosing prodromal
      states of Alzheimer's dementia, that is, mild cognitive impairment. Disease
      specific biomarkers for other degenerative dementias are still missing, but some
      progress has recently been made. As lumbar puncture is an additional burden for
      the patient, blood-based neurochemical biomarkers are definitely warranted and
      promising new discoveries have been made in this direction. These diagnostic
      developments have implicit therapeutic consequences and give rise to new
      requirements for future neurochemical dementia diagnostics.

PMID- 23139706
TI  - An update on the management of chronic inflammatory demyelinating polyneuropathy.
AB  - Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune mediated
      disorder of the peripheral nervous system with clinical features that include
      weakness, sensory loss, imbalance, pain and impaired ambulation which may lead to
      substantial disability. This review highlights current treatment strategies for
      CIDP, how best to utilize proven therapies such as intravenous immunoglobulin,
      oral prednisone, pulse dexamethasone, and plasma exchange, and when and how to
      use alternative immunosuppressive agents when first-line therapies are
      ineffective or poorly tolerated.

PMID- 23139708
TI  - Transarterial chemoembolization with/without cryotherapy is associated with
      improved clinical outcomes of sorafenib for the treatment of advanced
      hepatocellular carcinoma.
AB  - Sorafenib may prolong survival in patients with advanced hepatocellular carcinoma
      (HCC), but with limited efficacy. The present study aimed to prospectively
      investigate the efficacy and analyze the prognostic factors for survival in
      sorafenib-treated patients with advanced HCC. The baseline characteristics and
      clinical outcomes of 110 patients with advanced hepatitis B virus-related HCC
      treated with sorafenib with/without local therapy (transarterial
      chemoembolization with/without cryoablation) at a single liver cancer center were
      recorded. Predictors of progression-free survival (PFS) and overall survival (OS)
      were determined by multivariate analysis. A total of 14 (12.7%) patients achieved
      complete response (CR), 16 (14.5%) achieved partial response (PR) and 40 (36.4%)
      achieved stable disease (SD) lasting longer than 8 weeks. The median OS and PFS
      for the whole cohort were 10.5 [95% confidence interval (CI), 8.7-12.3] and 5.0
      months (95% CI, 3.7-6.3), respectively. Sorafenib in combination with local
      therapy was an independent predictor for longer PFS, whereas Eastern Cooperative
      Group (ECOG) performance status (PS) and Child-Pugh class were associated with
      reduced PFS. Local therapy was associated with longer OS while ECOG PS and alpha
      fetoprotein were associated with reduced OS. In a subset of patients with
      radiological progressive disease, a significant difference was found in OS
      between patients who continued taking sorafenib and those who discontinued
      therapy (11 vs. 7.5 months, P<0.001). In conclusion, sorafenib in combination
      with local therapy (transarterial chemoembolization with/without cryoablation)
      was independently associated with longer OS and PFS in advanced HCC patients.
      Poor ECOG PS was associated with shorter OS and PFS and is thus a marker of poor
      outcomes in sorafenib-treated HCC patients.

PMID- 23139709
TI  - Clinical utility of 18-fluorodeoxyglucose positron emission tomography/computed
      tomography in malignant pleural mesothelioma.
AB  - Malignant pleural mesothelioma (MPM) is an aggressive malignant tumor of
      mesothelial origin associated with asbestos exposure. MPM has a limited response
      to conventional chemotherapy and radiotherapy, thus early diagnosis of MPM is
      extremely critical. CT scans have limited accuracy in the differentiation between
      benign and malignant pleural disease. Several studies have reported that 18
      fluorodeoxyglucose (FDG) positron emission tomography (PET) plays an important
      role in the assessment of thoracic malignancy such as lung cancer. Here, we
      investigated the clinical utility of PET in patients with MPM. The maximum SUV
      (SUVmax) of 18F-FDG was measured in 47 MPM patients and 29 non-MPM patients
      including those with pleural thickening. We demonstrated that patients with MPM
      had significantly higher SUVmax levels than a population with non-malignant
      pleural disease. The Kaplan-Meier method revealed significant differences in
      overall survival between groups with SUVmax levels lower and higher than the
      assumed cut-off. Our data suggest that SUVmax levels are useful as an aid for
      diagnosis and prognosis of MPM.

PMID- 23139710
TI  - Vascular regeneration by pinpoint delivery of growth factors using a
      microcatheter reservoir system in a rabbit hind-limb ischemia model.
AB  - The purpose of this study was to compare the results of delivering low doses of
      growth factor iteratively (20 MUg x5) via a reservoir system with results
      obtained following a single administration of 100 MUg of growth factor. The
      delivery systems using gelatin microspheres (GMS) facilitate the controlled
      release of drugs. The controlled release of growth factors at specific sites is
      essential for vascular regeneration. An ischemic hind-limb model was established
      in nine rabbits. A reservoir system was implanted in each rabbit. GMS impregnated
      with basic fibroblast growth factor (bFGF) through an indwelling 2-Fr catheter
      was infused in the reservoir system. The rabbits were divided into three equal
      groups: group 1 received 20 MUg iteratively (x5) via the reservoir, a single dose
      of 100 MUg growth factor was administered to group 2 and group 3 was the saline
      control. The therapeutic effects were evaluated by measuring the thigh
      temperature, blood pressure and blood flow. An immunohistological analysis was
      also performed for CD31. No significant difference was observed between preand
      post-treatment (4 weeks following bFGF infusion) in the thigh temperature, blood
      pressure and blood flow results from each group. Pathological analysis revealed
      that the number of regenerated vessels was significantly higher in the group
      treated iteratively with low-dose bFGF.

PMID- 23139711
TI  - Dynamic tracing of immune cells in an orthotopic gastric carcinoma mouse model
      using near-infrared fluorescence live imaging.
AB  - Adoptive cellular immunotherapy (ACI) has been demonstrated to be a promising
      cancer therapeutic, however, the distribution of immune cells injected into a
      tumor-bearing body is unclear. In this study, we investigated the tumor-targeting
      capacity of cytokine-induced killer (CIK) cells and cytotoxic T lymphocytes
      (CTLs) in a human gastric carcinoma orthotopic mouse model using a near-infrared
      fluorescence imaging system. CIK cells and tumor-specific CTLs were prepared with
      the near-infrared fluorescent dye DiR. As expected, no significant change in the
      proliferation rate or antitumor activity of CIK cells and CTLs was noted after
      labeling with DiR. Furthermore, a gastric carcinoma orthotopic model was
      established using a fibrinogen-thrombin method in nude mice followed by
      intraperitoneal infusion of the labeled immune cells into nude mice with
      established gastric carcinoma. Dynamic tracing of the immune cells was performed
      using a fluorescence-based live imaging system. Concentrated fluorescence signals
      were observed for a minimum of two weeks at the tumor site in mice infused with
      either CIK cells or CTLs with a peak signal at 48 h. Notably, CTLs were more
      persistent at the tumor site and exhibited a more intense antitumor activity than
      CIK cells following infusion. These results provided visual evidence of the tumor
      targeting capacity of immune cells in live animals.

PMID- 23139712
TI  - Combinations of laminin 5 with PTEN, p-EGFR and p-Akt define a group of distinct
      molecular subsets indicative of poor prognosis in patients with non-small cell
      lung cancer.
AB  - Laminin 5 (Ln5) is an extracellular matrix protein that plays an important role
      in cell migration and tumor invasion. This study explored the expression of Ln5
      and the role of its relationships with PTEN, phospho-EGFR (p-EGFR) and phospho
      Akt (p-Akt) in the prognosis of patients with non-small cell lung cancer (NSCLC).
      The protein expression of Ln5, PTEN, p-EGFR and p-Akt was assessed by
      immunohistochemical analysis, and their relationships to prognosis were analyzed.
      Protein expression of Ln5, p-EGFR and p-Akt was detected in 61.2 (60/98), 60.2
      (59/98) and 45.3% (43/95) of patients with NSCLC, respectively. Loss of PTEN
      expression was found in 67.7% of tumors (65/96). Ln5 expression was related to
      patient gender, histology and p-Akt expression (chi(2)=3.901, 4.549 and 6.985,
      respectively; P=0.048, 0.033 and 0.008, respectively). Patients with positive Ln5
      expression had marginally poorer survival than Ln5-negative patients (median
      survival time 56.4 months vs. not reached; chi(2)=3.346; P=0.067). Overall
      survival was significantly different in patients with positive Ln5 expression
      combined with loss of PTEN, positive p-EGFR expression or positive p-Akt
      expression. Cox regression analysis showed that stage, co-expression of Ln5 and p
      Akt, and PTEN were the three most independent prognostic factors for patients
      with NSCLC (chi(2)=27.906; P<0.0005). The results highlight the complex
      relationships between extracellular matrix proteins and key signaling pathway
      molecules in tumorigenesis. Changes in the expression of Ln5 plus PTEN, p-EGFR or
      p-Akt define a distinct subset of lung cancers. Patients with such cancers have
      poorer survival and require early treatment that impacts survival.

PMID- 23139713
TI  - Neovascularization evaluated by CD105 correlates well with prognostic factors in
      breast cancers.
AB  - Angiogenesis is critical for the growth, invasion and metastasis of cancers.
      Extensive neovascularization and tumor thrombus also correlate with a poor
      prognosis in breast cancer (BC). Although anti-angiogenic agents have been the
      therapies of choice for BC, in particular for triple-negative BCs, predictive
      markers for anti-angiogenic agents are lacking. Microvascular density (MVD) is
      commonly used to assess the neovascularization in tumors. Compared with pan
      endothelial markers such as CD31, CD34 and von Willebrand factor (vWF), CD105 has
      a higher specificity for MVD in tumor tissues. In this study, we aimed to
      determine the prognostic value of CD105 in BCs. Paraffin-embedded tissue blocks
      from 201 BC patients were formed into tissue microarrays. Evaluation of MVD
      revealed that a median of 11 microvessels determined by CD105 staining correlated
      significantly with the pathological characteristics of BCs and also with the
      survival of patients. The expression of CD105 correlated inversely with hormone
      receptor (HR) expression but positively with Her-2 expression. Univariate
      analysis indicated that CD105 is a superior predictor of disease-free survival
      (DFS) in stage I and II diseases; multivariate analysis indicated that only
      hormone receptors (HRs) are suitable for predicting overall survival (OS) in
      stage III disease. These findings reveal for the first time that MVD measured by
      CD105 staining correlates positively with Her-2 expression but negatively with HR
      expression. The significance of MVD on OS is more apparent in early stage BCs.
      CD105 has the potential to be used as a predictive marker for anti-angiogenic
      agents; the targeting of CD105 may also be a potential anticancer strategy.

PMID- 23139714
TI  - Role of elevated liver transaminase levels in the diagnosis of liver injury after
      blunt abdominal trauma.
AB  - The liver is the second most commonly injured organ following blunt abdominal
      trauma. The stable patient with minimal physical findings with a history of blunt
      abdominal trauma presents a challenge for diagnosis of liver injury. This study
      was conducted to determine the usefulness of hepatic transaminases in predicting
      the presence of liver injury and its severity following blunt abdominal trauma.
      In this retrospective study, we included all patients who had sustained blunt
      abdominal injury and were treated at our institution between January 2008 and
      December 2010. The grading of the liver injury was verified using CT scans or
      surgical findings. One hundred and eighty-two patients with blunt abdominal
      trauma underwent the required blood tests and were included in the study. Using
      receiver operating characteristic (ROC) curve assessment, optimum alanine
      aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase
      (LDH) and gamma-glutamyl transpeptidase (GGT) thresholds were determined to be
      >57 U/l, 113 U/l, 595 U/l and 50 U/l. ALT >57 U/l (OR, 66.1; P<0.001) and AST
      >113 U/l (OR, 30.6; P<0.001) were strongly associated with the presence of liver
      injuries. This association was also observed in patients with elevated LDH >595
      U/l (OR, 3.8; P<0.001) and GGT >50 U/l (OR, 3.0; P<0.05). None of the laboratory
      tests were related to the severity of the liver injuries. In patients with blunt
      abdominal trauma, abnormal hepatic transaminase levels are associated with liver
      injuries. Patients with ALT >57 U/l and AST >113 U/l are strongly associated with
      liver injury and require further imaging studies and close management.

PMID- 23139715
TI  - K(ATP) channels mediate the antihypertrophic effects afforded by kappa-opioid
      receptor stimulation in neonatal rat ventricular myocytes.
AB  - Recent evidence suggests that kappa-opioid receptor (OR) agonists and K(ATP)
      channel activation exert antihypertrophic effects on cardiac myocytes. We studied
      the role of K(ATP) channels in the antihypertrophic effects of ORs in primary
      cultures of neonatal rat ventricular myocytes exposed for 48 h to the alpha(1)
      adrenoceptor agonist phenylephrine and the relative contributions of
      mitochondrial K(ATP) (mitoK(ATP)) and sarcolemmal K(ATP) (sarcK(ATP)).
      Furthermore, we elucidated the pathway between ORs and K(ATP) channels and their
      impact on intracellular Ca(2+) ([Ca(2+)](i)) transients. Hypertrophy of
      cardiomyocytes was characterized by increases in i) total protein content; ii)
      cell size and iii) [(3)H]leucine incorporation. Phenylephrine (10 MUM) increased
      the three parameters. Trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)
      cyclohexyl]-benzeneacetamid methanesulfonate salt (U50,488H), a selective kappa
      opioid receptor agonist, prevented phenylephrine-induced hypertrophy and
      [Ca(2+)](i) transients. The effect of U50,488H was abolished by nor
      binaltorphimine, a selective kappa-OR antagonist, indicating that the effect was
      kappa-OR-mediated. The protein kinase C inhibitor chelerythrine and the K(ATP)
      channel inhibitors glibenclamide (50 MUM), a nonselective K(ATP) antagonist, and
      5-hydroxydecanoic acid (100 MUM), a mitochondrial selective K(ATP) antagonist,
      reversed the antihypertrophic effect of U50,488H, and there was no significant
      difference between the two K(ATP) channel blockers. Moreover, we also determined
      the expression of the Kir6.2 subunits of the K(ATP) channel, which increased in
      response to U50,488H in the presence of phenylephrine, but was suppressed by
      chelerythrine, glibenclamide and 5-hydroxydecanoic acid. U50,488H also attenuated
      the elevation of [Ca(2+)](i). This study suggests that K(ATP), and particularly
      the mitochondrial K(ATP,) mediates the antihypertrophic effects of kappa-opioid
      receptor stimulation via the PKC signaling pathway.

PMID- 23139716
TI  - Synergistic effects of Endostar combined with beta-elemene on malignant ascites
      in a mouse model.
AB  - To explore an effective combination therapy for malignant ascites, the
      therapeutic value of the combination of Endostar, a modified recombinant human
      endostatin, and beta-elemene, an active component of a traditional Chinese herb,
      in an H22 mouse malignant ascites model was investigated. The optimal dose
      combination of Endostar and beta-elemene was determined by evaluating the
      inhibition of ascites volume and increase in the survival rate of the mice. Other
      therapeutic effects and the underlying mechanisms were investigated under the
      optimal dose combination (8 mg/kg Endostar plus 100 mg/kg beta-elemene). The mice
      were randomly divided into four treatment groups and received intraperitoneal
      injection once a day for eight days: control (0.9% normal saline), Endostar (8
      mg/kg), beta-elemene (100 mg/kg) or optimal dose combination (8 mg/kg Endostar
      plus 100 mg/kg beta-elemene), respectively. The results of this study revealed
      that the combination therapy had significant synergistic effects on the
      inhibition of ascites formation and a deceased number of tumor cells and protein
      levels in ascites compared with the results of treatment with a single agent. A
      decreased peritoneal microvascular permeability and reduction in VEGF, MMP-2 and
      hypoxia inducible factor 1alpha (HIF1alpha) was noted in the combination group,
      when compared with single agent treatment. These studies found that in the
      ascitic tumor cells, the protein levels of VEGF and MMP-2, as well as levels of
      VEGF mRNA, were significantly inhibited by the combination therapy. The
      potentiating effects of the combination of Endostar with beta-elemene suggest
      that this novel therapy may yield an effective therapy for the treatment of
      malignant ascites.

PMID- 23139717
TI  - Changes in intracellular redox status influence multidrug resistance in gastric
      adenocarcinoma cells.
AB  - Multidrug resistance (MDR) to chemotherapeutic agents is a major obstacle for the
      treatment of various types of cancers. The exact mechanism of MDR has not yet
      been fully clarified, although it has been frequently associated with the
      variation of intracellular redox status. The levels of intracellular glutathione
      (GSH) are considered to play a vital role in the regulation of the intracellular
      redox status. In our study, we investigated the effects of buthionine sulfoximine
      (BSO), an inhibitor of GSH biosynthesis, and NAC, a cysteine source for GSH
      synthesis, on sensitive gastric adenocarcinoma cells (SGC7901) and cisplatin
      resistant SGC7901/DDP cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay. The two cell lines were pretreated with
      various non-toxic concentrations of BSO for 24 h and combined with fluorouracil
      (5-FU) or mitomycin (MMC) in the presence or absence of NAC before culturing
      further. After various treatments, the IC(50) values of MMC and 5-FU were
      calculated and intracellular GSH levels were measured using the glutathione
      reductase/5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) recycling assay without
      anticancer drug stimulation under the same microenvironments. The study
      demonstrated that BSO increased the sensitivity of the cells to chemotherapeutics
      while NAC exhibited the reverse effect, particularly in drug-resistant cells. It
      is, therefore, possible that changes in intracellular GSH levels affect the
      chemosensitivity of the resistant cells to a greater extent than that of their
      parent cells. This study indicates that variation in the intracellular redox
      status may be closely correlated with MDR and may provide a valuable basic
      strategy for anticancer therapy.

PMID- 23139718
TI  - Hedyotis diffusa Willd extract inhibits HT-29 cell proliferation via cell cycle
      arrest.
AB  - Hedyotis diffusa Willd (HDW) has long been used as an important component in
      several Chinese medicine formulae to clinically treat various types of cancer,
      including colorectal cancer (CRC). Previously, we reported that HDW inhibits CRC
      growth via the induction of cancer cell apoptosis and the inhibition of tumor
      angiogenesis. In the present study, to further elucidate the mechanism of HDW
      mediated antitumor activity, we investigated the effect of HDW ethanol extract
      (EEHDW) on the proliferation of HT-29 human colon carcinoma cells. We found that
      EEHDW reduced HT-29 cell viability and survival in a dose- and time-dependent
      manner. We also observed that EEHDW treatment blocked the cell cycle, preventing
      G1 to S progression, and reduced mRNA expression of pro-proliferative PCNA,
      Cyclin D1 and CDK4, but increased that of anti-proliferative p21. Our findings
      suggest that Hedyotis diffusa Willd may be an effective treatment for CRC via the
      suppression of cancer cell proliferation.

PMID- 23139719
TI  - Prognostic significance of membrane-associated mucins 1 and 4 in gastric
      adenocarcinoma.
AB  - Aberrant expression of mucins is likely associated with cancer biology as
      alterations in the expression and/or glycosylation patterns of various mucins
      have been noted. Expression of the mucin family in gastric cancers has been
      reported in numerous studies, but the results are conflicting. Therefore, we
      investigated the potential use of mucin (MUC)1 and 4 as prognostic markers in
      gastric cancer according to histological subtype. Three-hundred and sixty-five
      gastric adenocarcinoma patients who underwent surgical resection were selected
      for this study. Among the 365 gastric cancer samples tested here, 34% consisted
      of early gastric cancer and 66% were advanced. In terms of location, 68.7% of the
      cohort had intestinal-type cancer and 30.7% had diffuse-type. We constructed
      tissue microarrays with formalin-fixed paraffin-embedded blocks of gastric cancer
      and these micro-arrays were evaluated for phenotypic expression of MUC1/4 using
      monoclonal antibodies. Two-hundred and ninety-two patients (92.7%) were positive
      for MUC1 and 216 (60.5%) were positive for MUC4. MUC1 expression was not
      correlated with any other clinicopathological variables such as age, gender,
      depth of invasion, lymph node metastasis, Lauren classification or recurrence.
      However, loss of MUC4 expression was significantly correlated with recurrence
      (p=0.033). MUC4 expression was also significantly correlated with better disease
      free survival (p=0.049) and particularly in the intestinal-type (p=0.018). Our
      present findings demonstrated that loss of MUC4 expression can be used as a
      prognostic marker in gastric cancer. Loss of MUC4 expression is a prognostic
      indicator of increased recurrence and poor disease-free survival in patients with
      gastric cancer.

PMID- 23139720
TI  - Comparison of docetaxel/cisplatin dosages of 75/60 and 60/60 mg/m(2) for the
      treatment of non-small cell lung cancer.
AB  - A combination of docetaxel (D) and cisplatin (P) is one of the standard regimens
      for the initial treatment of advanced non-small cell lung cancer (NSCLC). Yet,
      the toxicity of D administered at 75 mg/m(2) in three weekly doses to patients is
      a concern. The aim of this study was to assess the efficacy of a lower
      combination dose, 60 mg/m(2) of D and 60 mg/m(2) of cisplatin (P), as a treatment
      for NSCLC. In this randomized, phase III trial, we compared the response rates
      (RRs) and toxicity profiles of two combination regimens, D/P 75/60 vs. 60/60
      mg/m(2), to patients with stage IIIB or IV NSCLC. A total of 132 patients were
      randomized to the 75/60 (n=65) or 60/60 (n=67) dosage group. Non-inferiority of
      60/60 group compared to the 75/60 group was confirmed by the RR (38.5% for the
      75/60 group and 40.3% for the 60/60 group, 95% confidence interval -14.8 to 18.5,
      meeting the predefined non-inferiority criterion). The dose reduction rate and
      incidence of grade 3-4 neutropenia were significantly higher in the 75/60 group.
      The incidence of neutropenia was significantly higher in those with the non
      expressing genotype (GG) compared to the AG or AA genotypes of CYP3A5. We
      determined that DP 60/60 was not inferior to DP 75/60 in RR, and that the reduced
      combination dosage provides a better safety profile for patients.

PMID- 23139721
TI  - Challenges in the modification of the M1 stage of the TNM staging system for
      nasopharyngeal carcinoma: A study of 1027 cases and review of the literature.
AB  - A series of modifications have been introduced to the TNM staging system over
      time for nasopharyngeal carcinoma (NPC), mainly focused on the T (primary tumor)
      and N (local node) components of the system. The M1 stage is a 'catch all'
      classification, covering a group of patients whose outlook ranges from
      potentially curable to incurable. Since the current M1 stage does not allow
      clinicians to stratify patients according to prognosis or guide therapeutic
      decision-making and allow comparison of results of radical and non-radical
      treatments, we aimed to subdivide the M1 stage according to a retrospective study
      of 1027 metastatic NPC patients and to review the relevant literature. Between
      1995 and 2007, 1027 inpatients with distant metastasis from NPC were
      retrospectively analyzed. Various possible subdivisions of the M1 stage were
      considered, looking at different metastatic sites, the number of metastatic
      organs and the number of metastases. Survival rates were calculated using the
      Kaplan-Meier method and compared using the log-rank test. The most frequently
      involved metastatic sites were the bone, lung and liver. The incidence rates of
      solitary metastatic lesions and pulmonary metastasis were 16.2 and 41.3%. Despite
      the poor survival of these patients with a median survival of 30.8 months,
      patients in the metachronous metastatic group with metastases to the lung and/or
      solitary lesions, were defined as M1a, and were significantly associated with
      favorable median survival of 41.5 and 49.1 months in the univariate and
      multivariate analysis, respectively. Patients in the metachronous metastatic
      group with metastasis to the lung and/or solitary lesions (M1a) have a more
      favorable prognosis compared with those patients with multiple metastases located
      in other anatomic sites (M1b). These data, in one of the largest reported
      metastatic NPC cohorts, are the first to show the prognostic impact of metastatic
      status in NPC. As a powerful predictor, the potential clinical value of a
      modified M1 of the TNM system for NPC will facilitate patient counseling and
      individualize management.

PMID- 23139722
TI  - Tanshinone IIA inhibits the dihydrotestosterone-induced secretion of lipids and
      activation of sterol regulatory element binding protein-1 in HaCaT cells.
AB  - To study the effects and mechanisms of Tanshinone IIA (Tan IIA) on the
      dihydrotestosterone (DHT)-induced expression of sterol regulatory element binding
      protein-1 (SREBP-1), the synthesis and secretion of lipids in HaCaT cells were
      examined. HaCaT cells were treated with DHT and Tan IIA at different
      concentrations. Real-time PCR was used to detect the expression of SREBP-1c,
      fatty acid synthase (FAS), acyl-CoA synthetase (ACS), stearoyl-CoA desaturase
      (SCD) and HMG-CoA reductase (HMGCR) mRNA in HaCaT cells. Western blotting was
      used to analyze the protein expression of SREBP-1 and phosphorylation of Akt.
      Flow cytometry and Nile red staining were used to detect the synthesis and
      secretion of lipids in HaCaT cells. We observed that Tan IIA inhibited the DHT
      induced expression of SREBP-1 and p-AKT in HaCaT cells, which produced an effect
      similar to that of LY294002. Tan IIA significantly inhibited the transcription of
      lipid synthesis-related genes and decreased lipid secretion in HaCaT cells. In
      conclusion, Tan IIA downregulates the expression of lipid synthesis-related genes
      and decreases lipid secretion in HaCaT cells, which is correlated with the
      inhibitory effect on the DHT-induced mRNA and protein expression of SREBP-1 in
      HaCaT cells.

PMID- 23139723
TI  - Effects of rotenone on inducible nitric oxide synthase and cyclooxygenase-2 mRNA
      levels detected by real-time PCR in a rat bladder ischemia/reperfusion model.
AB  - We aimed to determine whether rotenone treatment prevents induced
      ischemia/reperfusion (I/R) damage in rat bladders by detecting inducible nitric
      oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) levels by real-time PCR (RT
      PCR). A total of 18 Sprague-Dawley albino rats were used in this experiment. The
      experimental groups each consisted of 6 rats and were treated as follows: group
      I, control; group II, I/R; group III, rotenone + I/R. In the control group, the
      rat bladders were removed by lower abdominal incision without any procedure. In
      the I/R group, 1 h prior to the ischemia 1 cc physiological serum was
      administered and the abdominal aortas were clamped for 1 h to achieve bladder
      ischemia. Following the ischemia, reperfusion was induced for 1 h and the
      bladders were removed. In the rotenone + I/R group, the rats were treated with 25
      mg/kg rotenone intraperitoneally. The iNOS and COX-2 mRNA levels in each group
      were detected using RT-PCR. In the I/R group, the COX-2 levels in the bladder
      tissue were higher compared with the control group (P<0.05). The COX-2 levels in
      the rotenone-treated group were statistically lower compared with the I/R group
      (P<0.01). Vascularization and edema were markedly increased in the I/R group.
      Following rotenone treatment these were abrogated inversely to inflammation.
      Although iNOS levels were slightly higher in the I/R group compared with the
      control group, iNOS levels did not decrease and no significant difference was
      observed between the groups with regard to rotenone treatment (P>0.05). We
      suggest that rotenone may be used clinically to treat I/R damage due to its
      diminishing effect on COX-2 levels.

PMID- 23139724
TI  - A Novel SNPs Detection Method Based on Gold Magnetic Nanoparticles Array and
      Single Base Extension.
AB  - To fulfill the increasing need for large-scale genetic research, a high
      throughput and automated SNPs genotyping method based on gold magnetic
      nanoparticles (GMNPs) array and dual-color single base extension has been
      designed. After amplification of DNA templates, biotinylated extension primers
      were captured by streptavidin coated gold magnetic nanoparticle (SA-GMNPs). Next
      a solid-phase, dual-color single base extension (SBE) reaction with the specific
      biotinylated primer was performed directly on the surface of the GMNPs. Finally,
      a "bead array" was fabricated by spotting GMNPs with fluorophore on a clean glass
      slide, and the genotype of each sample was discriminated by scanning the "bead
      array". MTHFR gene C677T polymorphism of 320 individual samples were interrogated
      using this method, the signal/noise ratio for homozygous samples were over 12.33,
      while the signal/noise ratio for heterozygous samples was near 1. Compared with
      other dual-color hybridization based genotyping methods, the method described
      here gives a higher signal/noise ratio and SNP loci can be identified with a high
      level of confidence. This assay has the advantage of eliminating the need for
      background subtraction and direct analysis of the fluorescence values of the
      GMNPs to determine their genotypes without the necessary procedures for
      purification and complex reduction of PCR products. The application of this
      strategy to large-scale SNP studies simplifies the process, and reduces the labor
      required to produce highly sensitive results while improving the potential for
      automation.

PMID- 23139725
TI  - Plasmonic nanobubbles rapidly detect and destroy drug-resistant tumors.
AB  - The resistance of residual cancer cells after oncological resection to adjuvant
      chemoradiotherapies results in both high recurrence rates and high non-specific
      tissue toxicity, thus preventing the successful treatment of such cancers as head
      and neck squamous cell carcinoma (HNSCC). The patients' survival rate and quality
      of life therefore depend upon the efficacy, selectivity and low non-specific
      toxicity of the adjuvant treatment. We report a novel, theranostic in vivo
      technology that unites both the acoustic diagnostics and guided intracellular
      delivery of anti-tumor drug (liposome-encapsulated doxorubicin, Doxil) in one
      rapid process, namely a pulsed laser-activated plasmonic nanobubble (PNB). HNSCC
      bearing mice were treated with gold nanoparticle conjugates, Doxil, and single
      near-infrared laser pulses of low energy. Tumor-specific clusters of gold
      nanoparticles (solid gold spheres) converted the optical pulses into localized
      PNBs. The acoustic signals of the PNB detected the tumor with high specificity
      and sensitivity. The mechanical impact of the PNB, co-localized with Doxil
      liposomes, selectively ejected the drug into the cytoplasm of cancer cells.
      Cancer cell-specific generation of PNBs and their intracellular co-localization
      with Doxil improved the in vivo therapeutic efficacy from 5-7% for administration
      of only Doxil or PNBs alone to 90% thus demonstrating the synergistic therapeutic
      effect of the PNB-based intracellular drug release. This mechanism also reduced
      the non-specific toxicity of Doxil below a detectable level and the treatment
      time to less than one minute. Thus PNBs combine highly sensitive diagnosis,
      overcome drug resistance and minimize non-specific toxicity in a single rapid
      theranostic procedure for intra-operative treatment.

PMID- 23139726
TI  - Optical imaging of tumors with copper-labeled rhodamine derivatives by targeting
      mitochondria.
AB  - In this study, we evaluated Cu(L1) in two xenografted tumor-bearing (U87MG and
      MDA-MB-435) animal models to prove the concept that Cu(II)-labeled rhodamine
      derivatives, Cu(L) (L = L1 - L4) are useful as selective fluorescent probes for
      tumor imaging. We found that both multidrug resistance (MDR) negative U87MG
      gliomas and MDR-positive MDA-MB-435 breast tumors could be visualized. Because of
      tissue attenuation, accurate quantification of tumor uptake was difficult by
      optical methods. Therefore, (64)Cu(L) (L = L1 - L4) were evaluated to compare
      their biodistribution properties. It was found that all four (64)Cu radiotracers
      had a high glioma uptake ((64)Cu(L1): 5.71+/- 1.43 %ID/g; (64)Cu(L2): 5.98 +/-
      2.75 %ID/g; (64)Cu(L3): 4.28 +/- 1.45 %ID/g; and (64)Cu(L4): 6.25 +/- 3.42 %ID/g)
      with (64)Cu(L1) showing the highest tumor/background ratios. In athymic nude mice
      bearing MDA-MB-435 breast cancer xenografts, (64)Cu(L4) showed almost identical
      normal organ uptake to that in the glioma-bearing animals, but its breast tumor
      uptake (1.26 +/- 0.10% ID/g) was significantly lower (p < 0.001) than that in the
      glioma (6.25 +/- 3.42% ID/g) because of MDR Pgps (P-glycoproteins) and MRPs
      (multidrug resistance-associated proteins) overexpressed in the xenografted MDA
      MB-435 breast tumors. Results from cellular staining assays showed that both
      Cu(L2) and Cu(L4) were able to localize in mitochondria of U87MG cells, and their
      tumor selectivity was caused by the elevated negative mitochondrial potential in
      U87MG glioma cells as compared to that in human fibroblast cells. On the basis of
      these results, it was concluded that Cu(L) (L = L1 - L4) are useful as selective
      fluorescent probes for cellular staining assays and optical tumor imaging while
      (64)Cu(L) (L = L1 - L4) have the potential as PET radiotracers for tumor imaging.
      This study represents a good example of dual modality imaging (PET and optical)
      using two agents, (64)Cu(L) and Cu(L), with identical chemical composition.
      Future research will focus on developing new fluorescent probes with longer
      wavelength and reduced liver uptake.

PMID- 23139727
TI  - Evaluation of an [(18)F]AlF-NOTA Analog of Exendin-4 for Imaging of GLP-1
      Receptor in Insulinoma.
AB  - INTRODUCTION: The GLP-1 receptor plays an important role in glucose homeostasis
      and thus is a very important target for diabetes therapy. The receptor is also
      overexpressed in insulinoma, a tumor of pancreatic beta-cells. We previously
      evaluated two fluorine-18-labeled analogs of exendin-4 prepared by conjugation
      with [(18)F]FBEM (N-[2-(4-[(18)F]fluorobenzamide)ethyl]maleimide). Both compounds
      demonstrated good tumor uptake, but the synthesis of the radiotracers was time
      consuming. To overcome this challenge, we developed a NOTA analog and performed
      radiolabeling using aluminum [(18)F]fluoride complexation. METHODS: Cys(40)
      exendin-4 was conjugated with NOTA mono N-ethylmaleimide. [(18)F]AlF conjugation
      was conducted and the radiolabeled product purified by preparative HPLC. Dynamic
      and static PET imaging scans were conducted on nude mice with established INS-1
      xenografts. Uptake of tumor and other major organs in static images was
      quantitated (%ID/g) and comparison with blocking studies was made. PET
      quantification was also compared with ex vivo biodistribution results. RESULTS:
      The radiosynthesis provided [(18)F]AlF-NOTA-MAL-cys(40)-exendin-4 in 23.6 +/- 2.4
      % radiochemical yield (uncorrected, n = 3) after HPLC; the process required about
      55 min. The specific activity at time of injection ranged from 19.6 to 31.4 GBq
      (0.53-0.85 Ci)/umol. Tumor uptake had reached its maximum (16.09 +/- 1.18% ID/g,
      n = 4) by 5 min and remained nearly constant for the duration of the study.
      Kidney uptake continued to increase throughout the entire one hour time course.
      Pre-injection of exendin-4 caused a marked reduction in tissue uptake with the
      major exception of liver and kidneys, in which uptake was not affected. HPLC
      analysis of the radioactive components in extracts of the tumor and plasma showed
      primarily parent compound at 60 min post-injection, whereas extracts of kidney
      and urine contained exclusively one polar radioactive component. CONCLUSION: The
      radiotracer is prepared in a simple one-step procedure and obtained in high
      specific activity after HPLC purification. [(18)F]AlF-NOTA-MAL-exendin-4 shows
      high tumor uptake and highly selective GLP-1 tissue uptake (INS-1 tumor, lung,
      pancreas), but still suffers from high kidney uptake.

PMID- 23139728
TI  - Exploring theranostic potentials of radioiodinated hypericin in rodent necrosis
      models.
AB  - OBJECTIVES: The present animal experiments were conducted to evaluate
      radioiodinated Hypericin (Hyp) for its regional distribution as well as
      theranostic potentials. MATERIALS AND METHODS: Rat models of reperfused liver
      infarction (RLI) and hepatic rhabdomyosarcoma (R1) were surgically induced. R1
      models received Combretastatin A4 phosphate (CA4P) intravenously at 10 mg/kg 24 h
      prior to radioiodinated Hyp. Three groups of 6 rats each containing 3 RLI and 3
      R1 models received iv injections of (123)I-Hyp at 37, 74, and 185 MBq/kg
      respectively and followed by 0.1 ml of 1% Evans blue solution were sacrificed at
      4, 24 and 48 hour post injection immediately after in vivo examination of MRI and
      planar gamma scintigraphy. Besides, two groups of 6 R1 models that received
      either 300 MBq/kg of (131)I-Hyp or vehicle intravenously were examined using MRI
      to compare tumor growth for 12 days. Autoradiography, gamma counting, and
      histopathology were performed for postmortem verifications and quantification.
      RESULTS: Necrosis as seen in vivo on contrast-enhanced MRI corresponded well with
      the hot spots on planar scintigraphy. Autoradiography and gamma counting revealed
      intense accumulation of (123)I-Hyp in necrotic liver (3.94 +/- 1.60, 5.38 +/-
      1.04, and 6.03 +/- 2.09 %ID/g +/- SD) and necrotic tumor (4.27 +/- 0.76, 5.57 +/-
      0.76, and 5.68 +/- 1.33 %ID/g +/- SD) relative to normal liver (1.76 +/- 0.54,
      0.41 +/- 0.18, and 0.16 +/- 0.07 %ID/g +/- SD), with a high necrosis-to-liver
      ratio of 2.3, 14.0, and 37.0 at 4, 24 and 48 h respectively. Tumor volumes in R1
      models that received (131)I-Hyp and vehicle changed from 0.45 +/- 0.09, and 0.47
      +/- 0.12 cm(3) (p > 0.05) on day 0 to1.32 +/- 0.76 and 3.63 +/- 0.72 cm(3 )(p <
      0.001) on day 12, with the corresponding necrosis ratios from 73 +/- 12 %, and 76
      +/- 17 % to 47 +/- 18% and 17 +/- 13 % (p < 0.01), and with the tumor DT of 7.3
      +/- 1.0 and 4.2 +/- 0.7 days, respectively. CONCLUSIONS: Radioiodinated Hyp as a
      necrosis avid tracer appears promising for non-invasive imaging diagnosis of
      necrosis-related pathologies. Its prominent targetability to necrosis allows
      targeted radiotherapy for malignancies on top of a prior necrosis-inducing
      treatment.

PMID- 23139729
TI  - Light-activated content release from liposomes.
AB  - Successful integration of diagnostic and therapeutic actions at the level of
      individual cells requires new materials that combine biological compatibility
      with functional versatility. This review focuses on the development of liposome
      based functional materials, where payload release is activated by light. Methods
      of sensitizing liposomes to light have progressed from the use of organic
      molecular moieties to the use of metallic plasmon resonant structures. This
      development has facilitated application of near infrared light for activation,
      which is preferred for its deep penetration and low phototoxicity in biological
      tissues. Presented mechanisms of light-activated liposomal content release enable
      precise in vitro manipulation of minute amounts of reagents, but their use in
      clinical diagnostic and therapeutic applications will require demonstration of
      safety and efficacy.

PMID- 23139730
TI  - Cardiogenic Regulation of Stem-Cell Electrical Properties in a Laser-Patterned
      Biochip.
AB  - Normal cardiomyocytes are highly dependent on the functional expression of ion
      channels to form action potentials and electrical coupling with other cells. To
      fully determine the scientific and therapeutic potential of stem cells for
      cardiovascular-disease treatment, it is necessary to assess comprehensively the
      regulation of stem-cell electrical properties during stem cell-cardiomyocyte
      interaction. It has been reported in the literature that contact with native
      cardiomyocytes induced and regulated stem-cell cardiogenic differentiation.
      However, in conventional cell-culture models, the importance of cell-cell contact
      for stem-cell functional coupling with cardiomyocytes has not been elucidated due
      to insufficient control of the cell-contact mode of individual cells. Using
      microfabrication and laser-guided cell micropatterning techniques, we created two
      biochips with contact-promotive and -preventive microenvironments to
      systematically study the effect of contact on cardiogenic regulation of stem-cell
      electrical properties. In contact-promotive biochips, connexin 43 expression was
      upregulated and relocated to the junction area between one stem cell and one
      cardiomyocyte. Only stem cells in contact with cardiomyocytes were induced by
      adjacent cardiomyocytes to acquire electrophysiological properties for action
      potential formation similar to that of a cardiomyocyte.

PMID- 23139731
TI  - Insights into Gene Expression and Packaging from Computer Simulations.
AB  - Within the nucleus of each cell lies DNA - an unfathomably long, twisted, and
      intricately coiled molecule - segments of which make up the genes that provide
      the instructions that a cell needs to operate. As we near the 60(th) anniversary
      of the discovery of the DNA double helix, crucial questions remain about how the
      physical arrangement of the DNA in cells affects how genes work. For example, how
      a cell stores the genetic information inside the nucleus is complicated by the
      necessity of maintaining accessibility to DNA for genetic processing. In order to
      gain insight into the roles played by various proteins in reading and compacting
      the genome, we have developed new methodologies to simulate the dynamic, three
      dimensional structures of long, fluctuating, protein-decorated strands of DNA.
      Our a priori approach to the problem allows us to determine the effects of
      individual proteins and their chemical modifications on overall DNA structure and
      function. Here we present our recent treatment of the communication between
      regulatory proteins attached to precisely constructed stretches of chromatin. Our
      simulations account for the enhancement in communication detected experimentally
      on chromatin compared to protein-free DNA of the same chain length as well as the
      critical roles played by the cationic 'tails' of the histone proteins in this
      signaling. The states of chromatin captured in the simulations offer new insights
      into the ways that the DNA, histones, and regulatory proteins contribute to long
      range communication along the genome.

PMID- 23139732
TI  - Dispersive Transport of Angiographic Contrast During Antegrade Arterial
      Injection.
AB  - PURPOSE: Angiography is commonly used during endovascular procedures to navigate
      catheters into a target artery and for evaluation of the arterial luminal
      geometry. X-ray attenuating contrast material is injected into the arteries and
      transported into pathologies such as aneurysms or arteriovenous malformations.
      Images of the transported contrast are used to guide therapeutic decisions.
      Experience and intuition of the interventionalist are often serving as guide for
      the injection force, and hence, the speed and volume of the bolus. Forceful
      injections of small boluses can evoke local turbulence and dispersive mixing in
      the zone immediately distal to the catheter tip. Turbulence by its nature acts as
      a strong agitating mechanism such that the bolus of contrast quickly mixes with
      the flowing blood to occupy the entire lumen so the artery can be visualized. The
      aims of the present study are (a) to determine the distance from catheter tip
      beyond which contrast can consider to be fully mixed with the blood during
      antegrade injection and (b) to determine the thickness of the boundary layer in
      which contrast concentration is poor, which can contribute to underestimation of
      vascular diameter using this method.  METHODS: We performed in silico experiments
      to describe blood and angiographic contrast transport in a straight artery model.
      The conditions investigated are derived from clinical contrast injection rates
      typically found in cerebral angiography.  RESULTS: A recirculation flow exists in
      the mixing zone distal to the catheter tip issuing the contrast and convective
      mixing rather than diffusion is dominating the rapid mixing process. In the
      vicinity of the arterial wall in the mass transfer boundary layer, however,
      transport is dominated by molecular diffusion. For lower molecule diffusion
      coefficient, the mass transfer boundary layer contains a lower concentration of
      contrast than for a higher molecular diffusion coefficient.  CONCLUSIONS: These
      findings imply that contrast visibility near the arterial wall is poor such that
      arterial dimensions derived from angiograms may be underestimated and
      consequently sizing of potential implants inaccurate. Outside the mass transfer
      boundary layer contrast can be considered as fully mixed with the carrying flow
      in about 10 arterial diameters distal to the injection port.

PMID- 23139733
TI  - Early Prevention of Severe Neurodevelopmental Behavior Disorders: An Integration.
AB  - There is a very substantial literature over the past 50 years on the advantages
      of early detection and intervention on the cognitive, communicative, and social
      emotional development of infants and toddlers at risk for developmental delay due
      to premature birth or social disadvantage. Most of these studies excluded
      children with severe delays or other predisposing conditions, such as genetic or
      brain disorders. Many studies of children with biological or socio-developmental
      risk suggest that behavior disorders appear as early as three years and persist
      into adulthood if not effectively treated. By contrast, little is known about the
      infants and toddlers with established risk for severe delays, who make up a
      significant proportion of the population with dual diagnoses later in life.In the
      past decade, there has been a growing interest in early detection and
      intervention with children aged birth to three years, e.g. the P.L.99-457, Part C
      Birth-Three population, who may have disabilities and severe behavior problems,
      e.g. aggression, self-injury, and repetitive stereotyped behaviors. The available
      research is scattered in the behavior analytic literature, in the child
      development literature, as well as in the child mental health and psychiatry
      literature, the developmental disability literature, the animal modeling
      literature, and the genetics literature. The goal of this introductory overview
      is to integrate these literatures, by cross-referencing members of these various
      groups who have worked in this field, in order to provide the reader with an
      integrated picture of what is known and of future directions that need more
      research.

PMID- 23139734
TI  - Estimation of distribution overlap of urn models.
AB  - A classical problem in statistics is estimating the expected coverage of a
      sample, which has had applications in gene expression, microbial ecology,
      optimization, and even numismatics. Here we consider a related extension of this
      problem to random samples of two discrete distributions. Specifically, we
      estimate what we call the dissimilarity probability of a sample, i.e., the
      probability of a draw from one distribution not being observed in [Formula: see
      text] draws from another distribution. We show our estimator of dissimilarity to
      be a [Formula: see text]-statistic and a uniformly minimum variance unbiased
      estimator of dissimilarity over the largest appropriate range of [Formula: see
      text]. Furthermore, despite the non-Markovian nature of our estimator when
      applied sequentially over [Formula: see text], we show it converges uniformly in
      probability to the dissimilarity parameter, and we present criteria when it is
      approximately normally distributed and admits a consistent jackknife estimator of
      its variance. As proof of concept, we analyze V35 16S rRNA data to discern
      between various microbial environments. Other potential applications concern any
      situation where dissimilarity of two discrete distributions may be of interest.
      For instance, in SELEX experiments, each urn could represent a random RNA pool
      and each draw a possible solution to a particular binding site problem over that
      pool. The dissimilarity of these pools is then related to the probability of
      finding binding site solutions in one pool that are absent in the other.

PMID- 23139735
TI  - Enhancement in motor learning through genetic manipulation of the Lynx1 gene.
AB  - The cholinergic system is a neuromodulatory neurotransmitter system involved in a
      variety of brain processes, including learning and memory, attention, and motor
      processes, among others. The influence of nicotinic acetylcholine receptors of
      the cholinergic system are moderated by lynx proteins, which are GPI-anchored
      membrane proteins forming tight associations with nicotinic receptors. Previous
      studies indicate lynx1 inhibits nicotinic receptor function and limits neuronal
      plasticity. We sought to investigate the mechanism of action of lynx1 on
      nicotinic receptor function, through the generation of lynx mouse models,
      expressing a soluble version of lynx and comparing results to the full length
      overexpression. Using rotarod as a test for motor learning, we found that
      expressing a secreted variant of lynx leads to motor learning enhancements
      whereas overexpression of full-length lynx had no effect. Further, adult lynx1KO
      mice demonstrated comparable motor learning enhancements as the soluble
      transgenic lines, whereas previously, aged lynx1KO mice showed performance
      augmentation only with nicotine treatment. From this we conclude the motor
      learning is more sensitive to loss of lynx function, and that the GPI anchor
      plays a role in the normal function of the lynx protein. In addition, our data
      suggests that the lynx gene plays a modulatory role in the brain during aging,
      and that a soluble version of lynx has potential as a tool for adjusting
      cholinergic-dependent plasticity and learning mechanisms in the brain.

PMID- 23139736
TI  - The importance of group-wise registration in tract based spatial statistics study
      of neurodegeneration: a simulation study in Alzheimer's disease.
AB  - Tract-based spatial statistics (TBSS) is a popular method for the analysis of
      diffusion tensor imaging data. TBSS focuses on differences in white matter voxels
      with high fractional anisotropy (FA), representing the major fibre tracts,
      through registering all subjects to a common reference and the creation of a FA
      skeleton. This work considers the effect of choice of reference in the TBSS
      pipeline, which can be a standard template, an individual subject from the study,
      a study-specific template or a group-wise average. While TBSS attempts to
      overcome registration error by searching the neighbourhood perpendicular to the
      FA skeleton for the voxel with maximum FA, this projection step may not
      compensate for large registration errors that might occur in the presence of
      pathology such as atrophy in neurodegenerative diseases. This makes registration
      performance and choice of reference an important issue. Substantial work in the
      field of computational anatomy has shown the use of group-wise averages to reduce
      biases while avoiding the arbitrary selection of a single individual. Here, we
      demonstrate the impact of the choice of reference on: (a) specificity (b)
      sensitivity in a simulation study and (c) a real-world comparison of Alzheimer's
      disease patients to controls. In (a) and (b), simulated deformations and
      decreases in FA were applied to control subjects to simulate changes of shape and
      WM integrity similar to what would be seen in AD patients, in order to provide a
      "ground truth" for evaluating the various methods of TBSS reference. Using a
      group-wise average atlas as the reference outperformed other references in the
      TBSS pipeline in all evaluations.

PMID- 23139737
TI  - Secreted aspartic protease cleavage of Candida albicans Msb2 activates Cek1 MAPK
      signaling affecting biofilm formation and oropharyngeal candidiasis.
AB  - Perception of external stimuli and generation of an appropriate response are
      crucial for host colonization by pathogens. In pathogenic fungi, mitogen
      activated protein kinase (MAPK) pathways regulate dimorphism, biofilm/mat
      formation, and virulence. Signaling mucins, characterized by a heavily
      glycosylated extracellular domain, a transmembrane domain, and a small
      cytoplasmic domain, are known to regulate various signaling pathways. In Candida
      albicans, the mucin Msb2 regulates the Cek1 MAPK pathway. We show here that Msb2
      is localized to the yeast cell wall and is further enriched on hyphal surfaces. A
      msb2Delta/Delta strain formed normal hyphae but had biofilm defects. Cek1 (but
      not Mkc1) phosphorylation was absent in the msb2Delta/Delta mutant. The
      extracellular domain of Msb2 was shed in cells exposed to elevated temperature
      and carbon source limitation, concomitant with germination and Cek1
      phosphorylation. Msb2 shedding occurred differentially in cells grown
      planktonically or on solid surfaces in the presence of cell wall and osmotic
      stressors. We further show that Msb2 shedding and Cek1 phosphorylation were
      inhibited by addition of Pepstatin A (PA), a selective inhibitor of aspartic
      proteases (Saps). Analysis of combinations of Sap protease mutants identified a
      sap8Delta/Delta mutant with reduced MAPK signaling along with defects in biofilm
      formation, thereby suggesting that Sap8 potentially serves as a major regulator
      of Msb2 processing. We further show that loss of either Msb2 (msb2Delta/Delta) or
      Sap8 (sap8Delta/Delta) resulted in higher C. albicans surface beta-glucan
      exposure and msb2Delta/Delta showed attenuated virulence in a murine model of
      oral candidiasis. Thus, Sap-mediated proteolytic cleavage of Msb2 is required for
      activation of the Cek1 MAPK pathway in response to environmental cues including
      those that induce germination. Inhibition of Msb2 processing at the level of Saps
      may provide a means of attenuating MAPK signaling and reducing C. albicans
      virulence.

PMID- 23139738
TI  - Genome-wide scan for bats and dolphin to detect their genetic basis for new
      locomotive styles.
AB  - For most mammals, running is their major locomotive style, however, cetaceans and
      bats are two mammalian groups that have independently developed new locomotive
      styles (swimming and flying) from their terrestrial ancestors. In this study, we
      used a genome-wide comparative analysis in an attempt to identify the selective
      imprint of the development of new locomotive styles by cetaceans and bats to
      adapt to their new ecological niches. We found that an elevated proportion of
      mitochondrion-associated genes show evidence of adaptive evolution in cetaceans
      and on the common ancestral lineage leading to bats, compared to other
      terrestrial mammals. This result is consistent with the fact that during the
      independent developments of swimming and flying in these two groups, the changes
      of energy metabolism ratios would be among the most important factors to overcome
      elevated energy demands. Furthermore, genes that show evidence of sequence
      convergence or parallel evolution in these two lineages were overrepresented in
      the categories of energy metabolism, muscle contraction, heart, and glucose
      metabolism, genes that perform functions which are essential for locomotion. In
      conclusion, our analyses showed that on the dolphin and bat lineages, genes
      associated with locomotion not only both show a greater propensity to adaptively
      evolve, but also show evidence of sequence convergence, which likely reflects a
      response to a common requirement during their development of these two drastic
      locomotive styles.

PMID- 23139739
TI  - N-chlorotaurine, a long-lived oxidant produced by human leukocytes, inactivates
      Shiga toxin of enterohemorrhagic Escherichia coli.
AB  - N-chlorotaurine (NCT), the main representative of long-lived oxidants produced by
      granulocytes and monocytes, is known to exert broad-spectrum microbicidal
      activity. Here we show that NCT directly inactivates Shiga toxin 2 (Stx2), used
      as a model toxin secreted by enterohemorrhagic Escherichia coli (EHEC). Bacterial
      growth and Stx2 production were both inhibited by 2 mM NCT. The cytotoxic effect
      of Stx2 on Vero cells was removed by >=5.5 mM NCT. Confocal microscopy and FACS
      analyses showed that the binding of Stx2 to human kidney glomerular endothelial
      cells was inhibited, and no NCT-treated Stx2 entered the cytosol. Mass
      spectrometry displayed oxidation of thio groups and aromatic amino acids of Stx2
      by NCT. Therefore, long-lived oxidants may act as powerful tools of innate
      immunity against soluble virulence factors of pathogens. Moreover, inactivation
      of virulence factors may contribute to therapeutic success of NCT and novel
      analogs, which are in development as topical antiinfectives.

PMID- 23139740
TI  - Estimation and discrimination of stochastic biochemical circuits from time-lapse
      microscopy data.
AB  - The ability of systems and synthetic biologists to observe the dynamics of
      cellular behavior is hampered by the limitations of the sensors, such as
      fluorescent proteins, available for use in time-lapse microscopy. In this paper,
      we propose a generalized solution to the problem of estimating the state of a
      stochastic chemical reaction network from limited sensor information generated by
      microscopy. We mathematically derive an observer structure for cells growing
      under time-lapse microscopy and incorporates the effects of cell division in
      order to estimate the dynamically-changing state of each cell in the colony.
      Furthermore, the observer can be used to discrimate between models by treating
      model indices as states whose values do not change with time. We derive necessary
      and sufficient conditions that specify when stochastic chemical reaction network
      models, interpreted as continuous-time Markov chains, can be distinguished from
      each other under both continual and periodic observation. We validate the
      performance of the observer on the Thattai-van Oudenaarden model of transcription
      and translation. The observer structure is most effective when the system model
      is well-parameterized, suggesting potential applications in synthetic biology
      where standardized biological parts are available. However, further research is
      necessary to develop computationally tractable approximations to the exact
      generalized solution presented here.

PMID- 23139741
TI  - Updating the salivary gland transcriptome of Phlebotomus papatasi (Tunisian
      strain): the search for sand fly-secreted immunogenic proteins for humans.
AB  - INTRODUCTION: Sand fly saliva plays an important role in both blood feeding and
      outcome of Leishmania infection. A cellular immune response against a Phlebotomus
      papatasi salivary protein was shown to protect rodents against Leishmania major
      infection. In humans, P. papatasi salivary proteins induce a systemic cellular
      immune response as well as a specific antisaliva humoral immune response, making
      these salivary proteins attractive targets as markers of exposure for this
      Leishmania vector. Surprisingly, the repertoire of salivary proteins reported for
      P. papatasi-a model sand fly for Leishmania-vector-host molecular interactions-is
      very limited compared with other sand fly species. We hypothesize that a more
      comprehensive study of the transcripts present in the salivary glands of P.
      papatasi will provide better knowledge of the repertoire of proteins of this
      important vector and will aid in selection of potential immunogenic proteins for
      humans and of those proteins that are highly conserved between different sand fly
      strains. METHODS AND FINDINGS: A cDNA library from P. papatasi (Tunisian strain)
      salivary glands was constructed, and randomly selected transcripts were sequenced
      and analyzed. The most abundant transcripts encoding secreted proteins were
      identified and compared with previously reported sequences. Importantly, we
      identified salivary proteins not described before in this sand fly species.
      CONCLUSIONS: Comparative analysis between the salivary proteins of P. papatasi
      from Tunisia and Israel strains shows a high level of identity, suggesting these
      proteins as potential common targets for markers of vector exposure or inducers
      of cellular immune responses in humans for different geographic areas.

PMID- 23139742
TI  - Functional analyses of endometriosis-related polymorphisms in the estrogen
      synthesis and metabolism-related genes.
AB  - Endometriosis is determined by genetic factors, and the prevalence of genetic
      polymorphisms varies greatly depending on the ethnic group studied. The objective
      of this study was to investigate the relationship between single nucleotide
      polymorphisms (SNPs) of 9 genes involved in estrogen biosynthesis and metabolism
      and the risks of endometriosis. Three hundred patients with endometriosis and 337
      non-endometriotic controls were recruited. Thirty four non-synonymous SNPs, which
      change amino acid residues, were analyzed using matrix-assisted laser desorption
      ionization time-of-flight mass spectrometry (MALDI-TOF MS). The functions of SNP
      resulted amino acid changes were analyzed using multiple web-accessible databases
      and phosphorylation predicting algorithms. Among the 34 NCBI-listed SNPs, 22 did
      not exhibit polymorphism in this study of more than 600 Taiwanese Chinese women.
      However, homozygous and heterozygous mutants of 4 SNPs - rs6165 (genotype GG+GA,
      307(Ala/Ala)+307(Ala/Thr)) of FSHR, rs 6166 (genotype GG+GA,
      680(Ser/Asn)+680(Ser/Ser)) of FSHR, rs2066479 (genotype AA+AG,
      289(Ser/Ser)+289(Ser/Gly)) of HSD17B3 and rs700519 (genotype TT+TC,
      264(Cys/Cys)+264(Cys/Arg)) of CYP19, alone or in combination, were significantly
      associated with decreased risks of endometriosis. Bioinformatics results
      identified 307(Thr) of FSHR to be a site for O-linked glycosylation, 680(Ser) of
      FSHR a phosphorylated site by protein kinase B, and 289(Ser) of HSD17B3 a
      phosphorylated site by protein kinase B or ribosomal protein S6 kinase 1. Results
      of this study suggest that non-synonymous polymorphisms of FSHR, HSD17B3 and
      CYP19 genes may modulate the risk of endometriosis in Taiwanese Chinese women.
      Identification of the endometrosis-preferential non-synonymous SNPs and the
      conformational changes in those proteins may pave the way for the development of
      more disease-specific drugs.

PMID- 23139743
TI  - Approaches to brain stress testing: BOLD magnetic resonance imaging with computer
      controlled delivery of carbon dioxide.
AB  - BACKGROUND: An impaired vascular response in the brain regionally may indicate
      reduced vascular reserve and vulnerability to ischemic injury. Changing the
      carbon dioxide (CO(2)) tension in arterial blood is commonly used as a cerebral
      vasoactive stimulus to assess the cerebral vascular response, changing cerebral
      blood flow (CBF) by up to 5-11 percent/mmHg in normal adults. Here we describe
      two approaches to generating the CO(2) challenge using a computer-controlled gas
      blender to administer: i) a square wave change in CO(2) and, ii) a ramp stimulus,
      consisting of a continuously graded change in CO(2) over a range. Responses were
      assessed regionally by blood oxygen level dependent (BOLD) magnetic resonance
      imaging (MRI). METHODOLOGY/PRINCIPAL FINDINGS: We studied 8 patients with known
      cerebrovascular disease (carotid stenosis or occlusion) and 2 healthy subjects.
      The square wave stimulus was used to study the dynamics of the vascular response,
      while the ramp stimulus assessed the steady-state response to CO(2).
      Cerebrovascular reactivity (CVR) maps were registered by color coding and
      overlaid on the anatomical scans generated with 3 Tesla MRI to assess the
      corresponding BOLD signal change/mmHg change in CO(2), voxel-by-voxel. Using a
      fractal temporal approach, detrended fluctuation analysis (DFA) maps of the
      processed raw BOLD signal per voxel over the same CO(2) range were generated.
      Regions of BOLD signal decrease with increased CO(2) (coded blue) were seen in
      all of these high-risk patients, indicating regions of impaired CVR. All patients
      also demonstrated regions of altered signal structure on DFA maps (Hurst
      exponents less than 0.5; coded blue) indicative of anti-persistent noise. While
      'blue' CVR maps remained essentially stable over the time of analysis, 'blue' DFA
      maps improved. CONCLUSIONS/SIGNIFICANCE: This combined dual stimulus and dual
      analysis approach may be complementary in identifying vulnerable brain regions
      and thus constitute a regional as well as global brain stress test.

PMID- 23139744
TI  - Basketball teams as strategic networks.
AB  - We asked how team dynamics can be captured in relation to function by considering
      games in the first round of the NBA 2010 play-offs as networks. Defining players
      as nodes and ball movements as links, we analyzed the network properties of
      degree centrality, clustering, entropy and flow centrality across teams and
      positions, to characterize the game from a network perspective and to determine
      whether we can assess differences in team offensive strategy by their network
      properties. The compiled network structure across teams reflected a fundamental
      attribute of basketball strategy. They primarily showed a centralized ball
      distribution pattern with the point guard in a leadership role. However,
      individual play-off teams showed variation in their relative involvement of other
      players/positions in ball distribution, reflected quantitatively by differences
      in clustering and degree centrality. We also characterized two potential
      alternate offensive strategies by associated variation in network structure: (1)
      whether teams consistently moved the ball towards their shooting specialists,
      measured as "uphill/downhill" flux, and (2) whether they distributed the ball in
      a way that reduced predictability, measured as team entropy. These network
      metrics quantified different aspects of team strategy, with no single metric
      wholly predictive of success. However, in the context of the 2010 play-offs, the
      values of clustering (connectedness across players) and network entropy
      (unpredictability of ball movement) had the most consistent association with team
      advancement. Our analyses demonstrate the utility of network approaches in
      quantifying team strategy and show that testable hypotheses can be evaluated
      using this approach. These analyses also highlight the richness of basketball
      networks as a dataset for exploring the relationships between network structure
      and dynamics with team organization and effectiveness.

PMID- 23139745
TI  - Large-scale screen for modifiers of ataxin-3-derived polyglutamine-induced
      toxicity in Drosophila.
AB  - Polyglutamine (polyQ) diseases represent a neuropathologically heterogeneous
      group of disorders. The common theme of these disorders is an elongated polyQ
      tract in otherwise unrelated proteins. So far, only symptomatic treatment can be
      applied to patients suffering from polyQ diseases. Despite extensive research,
      the molecular mechanisms underlying polyQ-induced toxicity are largely unknown.
      To gain insight into polyQ pathology, we performed a large-scale RNAi screen in
      Drosophila to identify modifiers of toxicity induced by expression of truncated
      Ataxin-3 containing a disease-causing polyQ expansion. We identified various
      unknown modifiers of polyQ toxicity. Large-scale analysis indicated a
      dissociation of polyQ aggregation and toxicity.

PMID- 23139746
TI  - The human homolog of Escherichia coli endonuclease V is a nucleolar protein with
      affinity for branched DNA structures.
AB  - Loss of amino groups from adenines in DNA results in the formation of
      hypoxanthine (Hx) bases with miscoding properties. The primary enzyme in
      Escherichia coli for DNA repair initiation at deaminated adenine is endonuclease
      V (endoV), encoded by the nfi gene, which cleaves the second phosphodiester bond
      3' of an Hx lesion. Endonuclease V orthologs are widespread in nature and belong
      to a family of highly conserved proteins. Whereas prokaryotic endoV enzymes are
      well characterized, the function of the eukaryotic homologs remains obscure. Here
      we describe the human endoV ortholog and show with bioinformatics and
      experimental analysis that a large number of transcript variants exist for the
      human endonuclease V gene (ENDOV), many of which are unlikely to be translated
      into functional protein. Full-length ENDOV is encoded by 8 evolutionary conserved
      exons covering the core region of the enzyme, in addition to one or more 3'-exons
      encoding an unstructured and poorly conserved C-terminus. In contrast to the E.
      coli enzyme, we find recombinant ENDOV neither to incise nor bind Hx-containing
      DNA. While both enzymes have strong affinity for several branched DNA substrates,
      cleavage is observed only with E. coli endoV. We find that ENDOV is localized in
      the cytoplasm and nucleoli of human cells. As nucleoli harbor the rRNA genes,
      this may suggest a role for the protein in rRNA gene transactions such as DNA
      replication or RNA transcription.

PMID- 23139747
TI  - Allele-level haplotype frequencies and pairwise linkage disequilibrium for 14 KIR
      loci in 506 European-American individuals.
AB  - The immune responses of natural killer cells are regulated, in part, by killer
      cell immunoglobulin-like receptors (KIR). The 16 closely-related genes in the KIR
      gene system have been diversified by gene duplication and unequal crossing over,
      thereby generating haplotypes with variation in gene copy number. Allelic
      variation also contributes to diversity within the complex. In this study, we
      estimated allele-level haplotype frequencies and pairwise linkage disequilibrium
      statistics for 14 KIR loci. The typing utilized multiple methodologies by four
      laboratories to provide at least 2x coverage for each allele. The computational
      methods generated maximum-likelihood estimates of allele-level haplotypes. Our
      results indicate the most extensive allele diversity was observed for the KIR
      framework genes and for the genes localized to the telomeric region of the KIR A
      haplotype. Particular alleles of the stimulatory loci appear to be nearly fixed
      on specific, common haplotypes while many of the less frequent alleles of the
      inhibitory loci appeared on multiple haplotypes, some with common haplotype
      structures. Haplotype structures cA01 and/or tA01 predominate in this cohort, as
      has been observed in most populations worldwide. Linkage disequilibrium is high
      within the centromeric and telomeric haplotype regions but not between them and
      is particularly strong between centromeric gene pairs KIR2DL5~KIR2DS3S5 and
      KIR2DS3S5~KIR2DL1, and telomeric KIR3DL1~KIR2DS4. Although 93% of the individuals
      have unique pairs of full-length allelic haplotypes, large genomic blocks sharing
      specific sets of alleles are seen in the most frequent haplotypes. These high
      resolution, high-quality haplotypes extend our basic knowledge of the KIR gene
      system and may be used to support clinical studies beyond single gene analysis.

PMID- 23139748
TI  - Hypoxia-induced modulation of apoptosis and BCL-2 family proteins in different
      cancer cell types.
AB  - Hypoxia plays an important role in the resistance of tumour cells to
      chemotherapy. However, the exact mechanisms underlying this process are not well
      understood. Moreover, according to the cell lines, hypoxia differently influences
      cell death. The study of the effects of hypoxia on the apoptosis induced by 5
      chemotherapeutic drugs in 7 cancer cell types showed that hypoxia generally
      inhibited the drug-induced apoptosis. In most cases, the effect of hypoxia was
      the same for all the drugs in one cell type. The expression profile of 93 genes
      involved in apoptosis as well as the protein level of BCL-2 family proteins were
      then investigated. In HepG2 cells that are strongly protected against cell death
      by hypoxia, hypoxia decreased the abundance of nearly all the pro-apoptotic BCL-2
      family proteins while none of them are decreased in A549 cells that are not
      protected against cell death by hypoxia. In HepG2 cells, hypoxia decreased NOXA
      and BAD abundance and modified the electrophoretic mobility of BIM(EL). BIM and
      NOXA are important mediators of etoposide-induced cell death in HepG2 cells and
      the hypoxia-induced modification of these proteins abundance or post
      translational modifications partly account for chemoresistance. Finally, the
      modulation of the abundance and/or of the post-translational modifications of
      most proteins of the BCL-2 family by hypoxia involves p53-dependent and 
      independent pathways and is cell type-dependent. A better understanding of these
      cell-to-cell variations is crucial in order to overcome hypoxia-induced
      resistance and to ameliorate cancer therapy.

PMID- 23139749
TI  - Submovement composition of head movement.
AB  - Limb movement is smooth and corrections of movement trajectory and amplitude are
      barely noticeable midflight. This suggests that skeletomuscular motor commands
      are smooth in transition, such that the rate of change of acceleration (or jerk)
      is minimized. Here we applied the methodology of minimum-jerk submovement
      decomposition to a member of the skeletomuscular family, the head movement. We
      examined the submovement composition of three types of horizontal head movements
      generated by nonhuman primates: head-alone tracking, head-gaze pursuit, and eye
      head combined gaze shifts. The first two types of head movements tracked a moving
      target, whereas the last type oriented the head with rapid gaze shifts toward a
      target fixed in space. During head tracking, the head movement was composed of a
      series of episodes, each consisting of a distinct, bell-shaped velocity profile
      (submovement) that rarely overlapped with each other. There was no specific
      magnitude order in the peak velocities of these submovements. In contrast, during
      eye-head combined gaze shifts, the head movement was often comprised of
      overlapping submovements, in which the peak velocity of the primary submovement
      was always higher than that of the subsequent submovement, consistent with the
      two-component strategy observed in goal-directed limb movements. These results
      extend the previous submovement composition studies from limb to head movements,
      suggesting that submovement composition provides a biologically plausible
      approach to characterizing the head motor recruitment that can vary depending on
      task demand.

PMID- 23139751
TI  - Exome sequencing of only seven Qataris identifies potentially deleterious
      variants in the Qatari population.
AB  - The Qatari population, located at the Arabian migration crossroads of African and
      Eurasia, is comprised of Bedouin, Persian and African genetic subgroups. By deep
      exome sequencing of only 7 Qataris, including individuals in each subgroup, we
      identified 2,750 nonsynonymous SNPs predicted to be deleterious, many of which
      are linked to human health, or are in genes linked to human health. Many of these
      SNPs were at significantly elevated deleterious allele frequency in Qataris
      compared to other populations worldwide. Despite the small sample size, SNP
      allele frequency was highly correlated with a larger Qatari sample. Together, the
      data demonstrate that exome sequencing of only a small number of individuals can
      reveal genetic variations with potential health consequences in understudied
      populations.

PMID- 23139750
TI  - Impaired Pten expression in human malignant peripheral nerve sheath tumours.
AB  - Malignant peripheral nerve sheath tumours (MPNST) are aggressive sarcomas that
      develop in about 10% of patients with the genetic disease neurofibromatosis type
      1 (NF1). Molecular alterations contributing to MPNST formation have only
      partially been resolved. Here we examined the role of Pten, a key regulator of
      the Pi3k/Akt/mTOR pathway, in human MPNST and benign neurofibromas.
      Immunohistochemistry showed that Pten expression was significantly lower in MPNST
      (n=16) than in neurofibromas (n=16) and normal nervous tissue. To elucidate
      potential mechanisms for Pten down-regulation or Akt/mTOR activation in MPNST we
      performed further experiments. Mutation analysis revealed absence of somatic
      mutations in PTEN (n=31) and PIK3CA (n=38). However, we found frequent PTEN
      promotor methylation in primary MPNST (11/26) and MPNST cell lines (7/8) but not
      in benign nerve sheath tumours. PTEN methylation was significantly associated
      with early metastasis. Moreover, we detected an inverse correlation of Pten
      regulating miR-21 and Pten protein levels in MPNST cell lines. The examination of
      NF1-/- and NF1+/+Schwann cells and fibroblasts showed that Pten expression is not
      regulated by NF1. To determine the significance of Pten status for treatment with
      the mTOR inhibitor rapamycin we treated 5 MPNST cell lines with rapamycin. All
      cell lines were sensitive to rapamycin without a significant correlation to Pten
      levels. When rapamycin was combined with simvastatin a synergistic anti
      proliferative effect was achieved. Taken together we show frequent loss/reduction
      of Pten expression in MPNST and provide evidence for the involvement of multiple
      Pten regulating mechanisms.

PMID- 23139752
TI  - Variations in mortality in children admitted with pneumonia to Kenyan hospitals.
AB  - BACKGROUND: The existing case fatality estimates of inpatient childhood pneumonia
      in developing countries are largely from periods preceding routine use of
      conjugate vaccines for infant immunization and such primary studies rarely
      explore hospital variations in mortality. We analysed case fatality rates of
      children admitted to nine Kenyan hospitals with pneumonia during the era of
      routine infant immunization with Hib conjugate vaccine to determine if
      significant variations exist between hospitals. METHODS: Pneumonia admissions and
      outcomes in paediatric wards are described using data collected over two time
      periods: a one-year period (2007-2008) in nine hospitals, and data from a 9.25
      year period (1999-March 2008) in one of the participating hospitals. Hospital
      case fatality rates for inpatient pneumonia during 2007 to 2008 were modeled
      using a fixed effect binomial regression model with a logit link. Using an
      interrupted time series design, data from one hospital were analysed for trends
      in pneumonia mortality during the period between 1997 and March 2008. RESULTS:
      Overall, 195 (5.9%) children admitted to all 9 hospitals with pneumonia from
      March 2007 to March 2008 died in hospital. After adjusting for child's sex,
      comorbidity, and hospital effect, mortality was significantly associated with
      child's age (p<0.001) and pneumonia severity (p<0.001). There was evidence of
      significant variations in mortality between hospitals (LR chi(2) =52.19;
      p<0.001). Pneumonia mortality remained stable in the periods before (trend -0.03,
      95% CI -0.1 to 0.02) and after Hib introduction (trend 0.04, 95% CI -0.04 to
      0.11). CONCLUSIONS: There are important variations in hospital-pneumonia case
      fatality in Kenya and these variations are not attributed to temporal changes.
      Such variations in mortality are not addressed by existing epidemiological models
      and need to be considered in allocating resources to improve child health.

PMID- 23139753
TI  - Human epididymis protein-4 (HE-4): a novel cross-class protease inhibitor.
AB  - Epididymal proteins represent the factors necessary for maturation of sperm and
      play a crucial role in sperm maturation. HE-4, an epididymal protein, is a member
      of whey acidic protein four-disulfide core (WFDC) family with no known function.
      A WFDC protein has a conserved WFDC domain of 50 amino acids with eight conserved
      cystine residue. HE-4 is a 124 amino acid long polypeptide with two WFDC domains.
      Here, we show that HE-4 is secreted in the human seminal fluid as a disulfide
      bonded homo-trimer and is a cross-class protease inhibitor inhibits some of the
      serine, aspartyl and cysteine proteases tested using hemoglobin as a substrate.
      Using SPR we have also observed that HE-4 shows a significant binding with all
      these proteases. Disulfide linkages are essential for this activity. Moreover, HE
      4 is N-glycosylated and highly stable on a wide range of pH and temperature.
      Taken together this suggests that HE-4 is a cross-class protease inhibitor which
      might confer protection against microbial virulence factors of proteolytic
      nature.

PMID- 23139754
TI  - Mannose-binding lectin regulates host resistance and pathology during
      experimental infection with Trypanosoma cruzi.
AB  - Mannose-binding lectin (MBL) is a humoral pattern-recognition molecule important
      for host defense. Although recent genetic studies suggest an involvement of
      MBL/MASP2-associated pathways in Chagas' disease, it is currently unknown whether
      MBL plays a role in host resistance to the intracellular protozoan Trypanosoma
      cruzi, the causative agent of Chagas' disease. In this study we employed MBL(-/-)
      mice to assess the role of MBL in resistance to experimental infection with T.
      cruzi. T. cruzi infection enhanced tissue expression of MBL both at the mRNA and
      protein level. Similarly, symptomatic acute Chagas' disease patients displayed
      increased serum concentrations of MBL compared to patients with indeterminate,
      asymptomatic forms of the disease. Furthermore, increased parasite loads in the
      blood and/or tissue were observed in MBL(-/-) mice compared to WT controls. This
      was associated with reduced systemic levels of IL-12/23p40 in MBL(-/-) mice.
      Importantly, MBL(-/-) mice infected with a cardiotropic strain of T. cruzi
      displayed increased myocarditis and cardiac fibrosis compared to WT controls. The
      latter was accompanied by elevated hydroxyproline content and mRNA levels of
      collagen-1 and -6 in the heart. These observations point to a previously
      unappreciated role for MBL in regulating host resistance and cardiac inflammation
      during infection with a major human pathogen.

PMID- 23139755
TI  - G-cimp status prediction of glioblastoma samples using mRNA expression data.
AB  - Glioblastoma Multiforme (GBM) is a tumor with high mortality and no known cure.
      The dramatic molecular and clinical heterogeneity seen in this tumor has led to
      attempts to define genetically similar subgroups of GBM with the hope of
      developing tumor specific therapies targeted to the unique biology within each of
      these subgroups. Recently, a subset of relatively favorable prognosis GBMs has
      been identified. These glioma CpG island methylator phenotype, or G-CIMP tumors,
      have distinct genomic copy number aberrations, DNA methylation patterns, and
      (mRNA) expression profiles compared to other GBMs. While the standard method for
      identifying G-CIMP tumors is based on genome-wide DNA methylation data, such data
      is often not available compared to the more widely available gene expression
      data. In this study, we have developed and evaluated a method to predict the G
      CIMP status of GBM samples based solely on gene expression data.

PMID- 23139756
TI  - Folliculin, the product of the Birt-Hogg-Dube tumor suppressor gene, interacts
      with the adherens junction protein p0071 to regulate cell-cell adhesion.
AB  - Birt-Hogg-Dube (BHD) is a tumor suppressor gene syndrome associated with
      fibrofolliculomas, cystic lung disease, and chromophobe renal cell carcinoma. In
      seeking to elucidate the pathogenesis of BHD, we discovered a physical
      interaction between folliculin (FLCN), the protein product of the BHD gene, and
      p0071, an armadillo repeat containing protein that localizes to the cytoplasm and
      to adherens junctions. Adherens junctions are one of the three cell-cell
      junctions that are essential to the establishment and maintenance of the cellular
      architecture of all epithelial tissues. Surprisingly, we found that
      downregulation of FLCN leads to increased cell-cell adhesion in functional cell
      based assays and disruption of cell polarity in a three-dimensional lumen-forming
      assay, both of which are phenocopied by downregulation of p0071. These data
      indicate that the FLCN-p0071 protein complex is a negative regulator of cell-cell
      adhesion. We also found that FLCN positively regulates RhoA activity and Rho
      associated kinase activity, consistent with the only known function of p0071.
      Finally, to examine the role of Flcn loss on cell-cell adhesion in vivo, we
      utilized keratin-14 cre-recombinase (K14-cre) to inactivate Flcn in the mouse
      epidermis. The K14-Cre-Bhd(flox/flox) mice have striking delays in eyelid
      opening, wavy fur, hair loss, and epidermal hyperplasia with increased levels of
      mammalian target of rapamycin complex 1 (mTORC1) activity. These data support a
      model in which dysregulation of the FLCN-p0071 interaction leads to alterations
      in cell adhesion, cell polarity, and RhoA signaling, with broad implications for
      the role of cell-cell adhesion molecules in the pathogenesis of human disease,
      including emphysema and renal cell carcinoma.

PMID- 23139757
TI  - Solution structure of a phytocystatin from Ananas comosus and its molecular
      interaction with papain.
AB  - The structure of a recombinant pineapple cystatin (AcCYS) was determined by NMR
      with the RMSD of backbone and heavy atoms of twenty lowest energy structures of
      0.56 and 1.11 A, respectively. It reveals an unstructured N-terminal extension
      and a compact inhibitory domain comprising a four-stranded antiparallel beta
      sheet wrapped around a central alpha-helix. The three structural motifs (G(45),
      Q(89)XVXG, and W(120)) putatively responsible for the interaction with papain
      like proteases are located in one side of AcCYS. Significant chemical shift
      perturbations in two loop regions, residues 45 to 48 (GIYD) and residues 89 to 91
      (QVV), of AcCYS strongly suggest their involvement in the binding to papain,
      consistent with studies on other members of the cystatin family. However, the
      highly conserved W120 appears not to be involved in the binding with papain as no
      chemical shift perturbation was observed. Chemical shift index analysis further
      indicates that the length of the alpha-helix is shortened upon association with
      papain. Collectively, our data suggest that AcCYS undergoes local secondary
      structural rearrangements when papain is brought into close contact. A molecular
      model of AcCYS/papain complex is proposed to illustrate the interaction between
      AcCYS and papain, indicating a complete blockade of the catalytic triad by AcCYS.

PMID- 23139758
TI  - Secondary sympatry caused by range expansion informs on the dynamics of
      microendemism in a biodiversity hotspot.
AB  - Islands are bounded areas where high endemism is explained either by allopatric
      speciation through the fragmentation of the limited amount of space available, or
      by sympatric speciation and accumulation of daughter species. Most empirical
      evidence point out the dominant action of allopatric speciation. We evaluate this
      general view by looking at a case study where sympatric speciation is suspected.
      We analyse the mode, tempo and geography of speciation in Agnotecous, a cricket
      genus endemic to New Caledonia showing a generalized pattern of sympatry between
      species making sympatric speciation plausible. We obtained five mitochondrial and
      five nuclear markers (6.8 kb) from 37 taxa corresponding to 17 of the 21 known
      extant species of Agnotecous, and including several localities per species, and
      we conducted phylogenetic and dating analyses. Our results suggest that the
      diversification of Agnotecous occurred mostly through allopatric speciation in
      the last 10 Myr. Highly microendemic species are the most recent ones (<2 Myr)
      and current sympatry is due to secondary range expansion after allopatric
      speciation. Species distribution should then be viewed as a highly dynamic
      process and extreme microendemism only as a temporary situation. We discuss these
      results considering the influence of climatic changes combined with intricate
      soil diversity and mountain topography. A complex interplay between these factors
      could have permitted repeated speciation events and range expansion.

PMID- 23139759
TI  - Maternal serum heme-oxygenase-1 (HO-1) concentrations in early pregnancy and
      subsequent risk of gestational diabetes mellitus.
AB  - BACKGROUND: Heme oxygenase-1 (HO-1) concentrations have been recently reported to
      be elevated in impaired glucose tolerance and type 2 diabetes mellitus (T2DM).
      However, no study has examined the association between HO-1 concentrations and
      gestational diabetes mellitus (GDM). METHODS: In a case-control study, nested
      within a prospective cohort of pregnant women (186 GDM cases and 191 women who
      remained eu-glycemic through pregnancy), we assessed the association of maternal
      serum HO-1 concentrations, measured in samples collected at 16 weeks gestation,
      on average, with subsequent risk of GDM. Maternal serum HO-1 concentrations were
      determined using ELISA. We fitted multivariate logistic regression models to
      derive estimates of odds ratios (ORs) and 95% confidence intervals (CIs).
      RESULTS: Median serum HO-1 concentrations in early pregnancy were lower in women
      who subsequently developed GDM compared with those who did not (1.60 vs. 1.80
      ng/mL, p-value=0.002). After adjusting for maternal age, race, family history of
      T2DM and pre-pregnancy body mass index, women with HO-1 >= 3.05 ng/mL (highest
      decile) experienced a 74% reduction of GDM risk (95% CI; 0.09-0.77) compared with
      women whose concentrations were<1.23 ng/mL (lowest quartile). CONCLUSION: Serum
      HO-1 concentrations were inversely associated with subsequent GDM risk. These
      findings underscore the role of oxidative stress in the pathogenesis of GDM.
      Additional studies are warranted to confirm the clinical utility of serum HO-1 in
      diagnosis of GDM, particularly in the early pregnancy.

PMID- 23139760
TI  - Knockout of insulin-like growth factor-1 receptor impairs distal lung
      morphogenesis.
AB  - BACKGROUND: Insulin-like growth factors (IGF-I and -II) are pleiotropic
      regulators of somatic growth and development in vertebrate species. Endocrine and
      paracrine effects of both hormones are mediated by a common IGF type 1 receptor
      (IGF-1R). Lethal respiratory failure in neonatal IGF-1R knockout mice suggested a
      particular role for this receptor in pulmonary development, and we therefore
      investigated the consequences of IGF-1R inactivation in lung tissue. METHODS AND
      FINDINGS: We first generated compound heterozygous mutant mice harboring a
      hypomorphic (Igf1r(neo)) and a null (Igf1r(-)) allele. These IGF-1R(neo/-) mice
      express only 22% of normal IGF-1R levels and are viable. In adult IGF-1R(neo/-)
      mice, we assessed lung morphology and respiratory physiology and found normal
      histomorphometric characteristics and normal breathing response to hypercapnia.
      We then generated homozygous IGF-1R knockout mutants (IGF-1R(-/-)) and analyzed
      their lung development during late gestation using histomorphometric and
      immunohistochemical methods. IGF-1R(-/-) embryos displayed severe lung hypoplasia
      and markedly underdeveloped diaphragms, leading to lethal neonatal respiratory
      distress. Importantly, IGF-1R(-/-) lungs from late gestation embryos were four
      times smaller than control lungs and showed markedly thickened intersaccular
      mesenchyme, indicating strongly delayed lung maturation. Cell proliferation and
      apoptosis were significantly increased in IGF-1R(-/-) lung tissue as compared
      with IGF-1R(+/+) controls. Immunohistochemistry using pro-SP-C, NKX2-1, CD31 and
      vWF as markers revealed a delay in cell differentiation and arrest in the
      canalicular stage of prenatal respiratory organ development in IGF-1R(-/-) mutant
      mice. CONCLUSIONS/SIGNIFICANCE: We found that low levels of IGF-1R were
      sufficient to ensure normal lung development in mice. In contrast, complete
      absence of IGF-1R significantly delayed end-gestational lung maturation. Results
      indicate that IGF-1R plays essential roles in cell proliferation and timing of
      cell differentiation during fetal lung development.

PMID- 23139761
TI  - Protein fragments: functional and structural roles of their coevolution networks.
AB  - Small protein fragments, and not just residues, can be used as basic building
      blocks to reconstruct networks of coevolved amino acids in proteins. Fragments
      often enter in physical contact one with the other and play a major biological
      role in the protein. The nature of these interactions might be multiple and spans
      beyond binding specificity, allosteric regulation and folding constraints.
      Indeed, coevolving fragments are indicators of important information explaining
      folding intermediates, peptide assembly, key mutations with known roles in
      genetic diseases, distinguished subfamily-dependent motifs and differentiated
      evolutionary pressures on protein regions. Coevolution analysis detects networks
      of fragments interaction and highlights a high order organization of fragments
      demonstrating the importance of studying at a deeper level this structure. We
      demonstrate that it can be applied to protein families that are highly conserved
      or represented by few sequences, enlarging in this manner, the class of proteins
      where coevolution analysis can be performed and making large-scale coevolution
      studies a feasible goal.

PMID- 23139762
TI  - Crowding effects in vehicular traffic.
AB  - While the impact of crowding on the diffusive transport of molecules within a
      cell is widely studied in biology, it has thus far been neglected in traffic
      systems where bulk behavior is the main concern. Here, we study the effects of
      crowding due to car density and driving fluctuations on the transport of
      vehicles. Using a microscopic model for traffic, we found that crowding can push
      car movement from a superballistic down to a subdiffusive state. The transition
      is also associated with a change in the shape of the probability distribution of
      positions from a negatively-skewed normal to an exponential distribution.
      Moreover, crowding broadens the distribution of cars' trap times and cluster
      sizes. At steady state, the subdiffusive state persists only when there is a
      large variability in car speeds. We further relate our work to prior findings
      from random walk models of transport in cellular systems.

PMID- 23139763
TI  - Muscle, skin and core temperature after -110 degrees c cold air and 8 degrees c
      water treatment.
AB  - The aim of this investigation was to elucidate the reductions in muscle, skin and
      core temperature following exposure to -110 degrees C whole body cryotherapy
      (WBC), and compare these to 8 degrees C cold water immersion (CWI). Twenty active
      male subjects were randomly assigned to a 4-min exposure of WBC or CWI. A minimum
      of 7 days later subjects were exposed to the other treatment. Muscle temperature
      in the right vastus lateralis (n=10); thigh skin (average, maximum and minimum)
      and rectal temperature (n=10) were recorded before and 60 min after treatment.
      The greatest reduction (P<0.05) in muscle (mean +/- SD; 1 cm: WBC, 1.6 +/- 1.2
      degrees C; CWI, 2.0 +/- 1.0 degrees C; 2 cm: WBC, 1.2 +/- 0.7 degrees C; CWI, 1.7
      +/- 0.9 degrees C; 3 cm: WBC, 1.6 +/- 0.6 degrees C; CWI, 1.7 +/- 0.5 degrees C)
      and rectal temperature (WBC, 0.3 +/- 0.2 degrees C; CWI, 0.4 +/- 0.2 degrees C)
      were observed 60 min after treatment. The largest reductions in average (WBC,
      12.1 +/- 1.0 degrees C; CWI, 8.4 +/- 0.7 degrees C), minimum (WBC, 13.2 +/- 1.4
      degrees C; CWI, 8.7 +/- 0.7 degrees C) and maximum (WBC, 8.8 +/- 2.0 degrees C;
      CWI, 7.2 +/- 1.9 degrees C) skin temperature occurred immediately after both CWI
      and WBC (P<0.05). Skin temperature was significantly lower (P<0.05) immediately
      after WBC compared to CWI. The present study demonstrates that a single WBC
      exposure decreases muscle and core temperature to a similar level of those
      experienced after CWI. Although both treatments significantly reduced skin
      temperature, WBC elicited a greater decrease compared to CWI. These data may
      provide information to clinicians and researchers attempting to optimise WBC and
      CWI protocols in a clinical or sporting setting.

PMID- 23139765
TI  - Top-down feedback in an HMAX-like cortical model of object perception based on
      hierarchical Bayesian networks and belief propagation.
AB  - Hierarchical generative models, such as Bayesian networks, and belief propagation
      have been shown to provide a theoretical framework that can account for
      perceptual processes, including feedforward recognition and feedback modulation.
      The framework explains both psychophysical and physiological experimental data
      and maps well onto the hierarchical distributed cortical anatomy. However, the
      complexity required to model cortical processes makes inference, even using
      approximate methods, very computationally expensive. Thus, existing object
      perception models based on this approach are typically limited to tree-structured
      networks with no loops, use small toy examples or fail to account for certain
      perceptual aspects such as invariance to transformations or feedback
      reconstruction. In this study we develop a Bayesian network with an architecture
      similar to that of HMAX, a biologically-inspired hierarchical model of object
      recognition, and use loopy belief propagation to approximate the model operations
      (selectivity and invariance). Crucially, the resulting Bayesian network extends
      the functionality of HMAX by including top-down recursive feedback. Thus, the
      proposed model not only achieves successful feedforward recognition invariant to
      noise, occlusions, and changes in position and size, but is also able to
      reproduce modulatory effects such as illusory contour completion and attention.
      Our novel and rigorous methodology covers key aspects such as learning using a
      layerwise greedy algorithm, combining feedback information from multiple parents
      and reducing the number of operations required. Overall, this work extends an
      established model of object recognition to include high-level feedback
      modulation, based on state-of-the-art probabilistic approaches. The methodology
      employed, consistent with evidence from the visual cortex, can be potentially
      generalized to build models of hierarchical perceptual organization that include
      top-down and bottom-up interactions, for example, in other sensory modalities.

PMID- 23139764
TI  - Spatiotemporal and functional characterisation of the Plasmodium falciparum cGMP
      dependent protein kinase.
AB  - Signalling by 3'-5'-cyclic guanosine monophosphate (cGMP) exists in virtually all
      eukaryotes. In the apicomplexan parasite Plasmodium, the cGMP-dependent protein
      kinase (PKG) has previously been reported to play a critical role in four key
      stages of the life cycle. The Plasmodium falciparum isoform (PfPKG) is essential
      for the initiation of gametogenesis and for blood stage schizont rupture and work
      on the orthologue from the rodent malaria parasite P. berghei (PbPKG) has shown
      additional roles in ookinete differentiation and motility as well as liver stage
      schizont development. In the present study, PfPKG expression and subcellular
      location in asexual blood stages was investigated using transgenic epitope-tagged
      PfPKG-expressing P. falciparum parasites. In Western blotting experiments and
      immunofluorescence analysis (IFA), maximal PfPKG expression was detected at the
      late schizont stage. While IFA suggested a cytosolic location, a degree of
      overlap with markers of the endoplasmic reticulum (ER) was found and subcellular
      fractionation showed some association with the peripheral membrane fraction. This
      broad localisation is consistent with the notion that PfPKG, as with the
      mammalian orthologue, has numerous cellular substrates. This idea is further
      supported by the global protein phosphorylation pattern of schizonts which was
      substantially changed following PfPKG inhibition, suggesting a complex role for
      PfPKG during schizogony.

PMID- 23139766
TI  - CNS SIRT3 expression is altered by reactive oxygen species and in Alzheimer's
      disease.
AB  - Progressive mitochondrial dysfunction contributes to neuronal degeneration in age
      mediated disease. An essential regulator of mitochondrial function is the
      deacetylase, sirtuin 3 (SIRT3). Here we investigate a role for CNS Sirt3 in
      mitochondrial responses to reactive oxygen species (ROS)- and Alzheimer's disease
      (AD)-mediated stress. Pharmacological augmentation of mitochondrial ROS increases
      Sirt3 expression in primary hippocampal culture with SIRT3 over-expression being
      neuroprotective. Furthermore, Sirt3 expression mirrors spatiotemporal deposition
      of beta-amyloid in an AD mouse model and is also upregulated in AD patient
      temporal neocortex. Thus, our data suggest a role for SIRT3 in mechanisms sensing
      and tackling ROS- and AD-mediated mitochondrial stress.

PMID- 23139767
TI  - Homocysteine induces apoptosis of rat hippocampal neurons by inhibiting 14-3
      3epsilon expression and activating calcineurin.
AB  - A high level of plasma homocysteine (Hcy) increases the risk for
      neurodegenerative diseases. One such disorder is Alzheimer's disease, which
      involves marked neuronal apoptosis of unknown etiology. This study shows that Hcy
      inhibits expression of 14-3-3epsilon and activates calcineurin in rat hippocampal
      neurons in a dose-dependent manner. Calcineurin-mediated Bad dephosphorylation,
      which is blocked by calcineurin inhibition and Ca(2+) chelation, causes
      mitochondrial translocation of Bad and apoptosis; this step in the apoptotic
      pathway is synergistically blocked by calcineurin inhibition and overexpression
      of 14-3-3epsilon. These findings demonstrated that calcineurin activation and
      downregulation of 14-3-3epsilon may be one of the mechanisms of Hcy-induced
      apoptosis of hippocampal neurons.

PMID- 23139768
TI  - Evaluation of a multicore-optimized implementation for tomographic
      reconstruction.
AB  - Tomography allows elucidation of the three-dimensional structure of an object
      from a set of projection images. In life sciences, electron microscope tomography
      is providing invaluable information about the cell structure at a resolution of a
      few nanometres. Here, large images are required to combine wide fields of view
      with high resolution requirements. The computational complexity of the algorithms
      along with the large image size then turns tomographic reconstruction into a
      computationally demanding problem. Traditionally, high-performance computing
      techniques have been applied to cope with such demands on supercomputers,
      distributed systems and computer clusters. In the last few years, the trend has
      turned towards graphics processing units (GPUs). Here we present a detailed
      description and a thorough evaluation of an alternative approach that relies on
      exploitation of the power available in modern multicore computers. The
      combination of single-core code optimization, vector processing, multithreading
      and efficient disk I/O operations succeeds in providing fast tomographic
      reconstructions on standard computers. The approach turns out to be competitive
      with the fastest GPU-based solutions thus far.

PMID- 23139769
TI  - CYP2E1 RsaI/PstI polymorphism and gastric cancer susceptibility: meta-analyses
      based on 24 case-control studies.
AB  - BACKGROUND: Previous reports implicate CYP2E1 RsaI/PstI polymorphism as a
      possible risk factor for several cancers. Published studies on the relationship
      of CYP2E1 RsaI/PstI polymorphisms with the susceptibility to gastric cancer are
      controversial. This study aimed to determine this relationship accurately.
      METHODS: Meta-analyses that assessed the association of CYP2E1 RsaI/PstI
      variations with gastric cancer were conducted. Subgroup analyses on ethnicity,
      smoking status, alcohol consumption, and source of controls were also performed.
      Eligible studies up to Mar 2012 were identified. RESULTS: After rigorous
      searching and screening, 24 case-control studies comprising 3022 cases and 4635
      controls were selected for analysis. The overall data failed to indicate the
      significant associations of CYP2E1 RsaI/PstI polymorphisms with the gastric
      cancer risk [c2 vs. c1: odds ratio (OR) =1.06; 95% confidence interval (CI) =0.88
      1.28; c2c2 vs. c1c1: OR=1.23; 95% CI=0.78-1.92; c2c2+c1c2 vs. c1c1: OR=0.93; 95%
      CI=0.79-1.10]. Similar results were observed in the subgroup analyses on
      ethnicity, drinking status, and source of controls. However, in the subgroup
      analysis on smoking status, a borderline increase in cancer risk was found among
      long-term smokers (c2c2+c1c2 vs. c1c1: OR=1.39; 95% CI=1.00-1.92). CONCLUSION:
      CYP2E1 RsaI/PstI polymorphisms may modify the susceptibility to gastric cancer
      among individuals who have a smoking history. Large and well-designed studies are
      needed to confirm this conclusion.

PMID- 23139771
TI  - Pioglitazone improves in vitro viability and function of endothelial progenitor
      cells from individuals with impaired glucose tolerance.
AB  - BACKGROUND: Evidence suggests that the PPARgamma-agonist insulin sensitizer
      pioglitazone, may provide potential beneficial cardiovascular (CV) effects beyond
      its anti-hyperglycaemic function. A reduced endothelial progenitor cell (EPC)
      number is associated with impaired glucose tolerance (IGT) or diabetes,
      conditions characterised by increased CV risk. AIM: To evaluate whether
      pioglitazone can provide benefit in vitro in EPCs obtained from IGT subjects.
      MATERIALS AND METHODS: Early and late-outgrowth EPCs were obtained from
      peripheral blood mononuclear cells of 14 IGT subjects. The in vitro effect of
      pioglitazone (10 uM) with/without PPARgamma-antagonist GW9662 (1 uM) was assessed
      on EPC viability, apoptosis, ability to form tubular-like structures and pro
      inflammatory molecule expression. RESULTS: Pioglitazone increased early and late
      outgrowth EPC viability, with negligible effects on apoptosis. The capacity of
      EPCs to form tubular-like structures was improved by pioglitazone in early (mean
      increase 28%; p=0.005) and late-outgrowth (mean increase 30%; p=0.037) EPCs.
      Pioglitazone reduced ICAM-1 and VCAM-1 adhesion molecule expression in both early
      (p=0.001 and p=0.012 respectively) and late-outgrowth (p=0.047 and p=0.048,
      respectively) EPCs. Similarly, pioglitazone reduced TNFalpha gene and protein
      expression in both early (p=0.034;p=0.022) and late-outgrowth (p=0.026;p=0.017)
      EPCs compared to control. These effects were prevented by incubation with the
      PPARgamma-antagonist GW9662. CONCLUSION: Pioglitazone exerts beneficial effects
      in vitro on EPCs isolated from IGT subjects, supporting the potential implication
      of pioglitazone as a CV protective agents.

PMID- 23139772
TI  - Remote ischemic preconditioning (RIPC) modifies plasma proteome in humans.
AB  - Remote Ischemic Preconditioning (RIPC) induced by brief episodes of ischemia of
      the limb protects against multi-organ damage by ischemia-reperfusion (IR).
      Although it has been demonstrated that RIPC affects gene expression, the
      proteomic response to RIPC has not been determined. This study aimed to examine
      RIPC induced changes in the plasma proteome. Five healthy adult volunteers had 4
      cycles of 5 min ischemia alternating with 5 min reperfusion of the forearm. Blood
      samples were taken from the ipsilateral arm prior to first ischaemia, immediately
      after each episode of ischemia as well as, at 15 min and 24 h after the last
      episode of ischemia. Plasma samples from five individuals were analysed using two
      complementary techniques. Individual samples were analysed using 2Dimensional
      Difference in gel electrophoresis (2D DIGE) and mass spectrometry (MS). Pooled
      samples for each of the time-points underwent trypsin digestion and peptides
      generated were analysed in triplicate using Liquid Chromatography and MS (LC-MS).
      Six proteins changed in response to RIPC using 2D DIGE analysis, while 48
      proteins were found to be differentially regulated using LC-MS. The proteins of
      interest were involved in acute phase response signalling, and physiological
      molecular and cellular functions. The RIPC stimulus modifies the plasma protein
      content in blood taken from the ischemic arm in a cumulative fashion and evokes a
      proteomic response in peripheral blood.

PMID- 23139770
TI  - Regulation of MMP-9 by a WIN-binding site in the monocyte-macrophage system
      independent from cannabinoid receptors.
AB  - The cannabinoid system is known to be involved in the regulation of inflammatory
      processes. Therefore, drugs targeting cannabinoid receptors are considered as
      candidates for anti-inflammatory and tissue protective therapy. We demonstrated
      that the prototypical cannabinoid agonist R(+)WIN55,212-2 (WIN) reduced the
      secretion of matrix metalloproteinase-9 (MMP-9) in a murine model of cigarette
      smoke induced lung inflammation. In experiments using primary cells and cell
      lines of the monocyte-macrophage-system we found that binding of the cannabinoid
      receptor agonist WIN to a stereo-selective, specific binding site in cells of the
      monocyte-macrophage-system induced a significant down-regulation of MMP-9
      secretion and disturbance of intracellular processing, which subsequently down
      regulated MMP-9 mRNA expression via a ERK1/2-phosphorylation-dependent pathway.
      Surprisingly, the anti-inflammatory effect was independent from classical
      cannabinoid receptors. Our experiments supposed an involvement of TRPV1, but
      other yet unidentified sites are also possible. We conclude that cannabinoid
      induced control of MMP-9 in the monocyte-macrophage system via a cannabinoid
      receptor independent pathway represents a general option for tissue protection
      during inflammation, such as during lung inflammation and other diseases
      associated with inflammatory tissue damage.

PMID- 23139773
TI  - The association of RAS association domain family Protein1A (RASSF1A) methylation
      states and bladder cancer risk: a systematic review and meta-analysis.
AB  - RAS association domain family protein 1a (RASSF1A) is a putative tumor suppressor
      gene located on 3p21, has been regarded playing important roles in the regulation
      of different types of human tumors. Previous reports demonstrated that the
      frequency of RASSF1A methylation was significantly higher in patients group
      compared with controls, but the relationship between RASSF1A promoter methylation
      and pathological features or the tumor grade of bladder cancer remains
      controversial. Therefore, A meta-analysis of published studies investigating the
      effects of RASSF1A methylation status in bladder cancer occurrence and
      association with both pTNM (p, pathologic stage; T, tumor size; N, node status;
      M, metastatic status) and tumor grade in bladder cancer was performed in the
      study. A total of 10 eligible studies involving 543 cases and 217 controls were
      included in the pooled analyses. Under the fixed-effects model, the OR of RASSF1A
      methylation in bladder cancer patients, compared to non-cancer controls, was 8.
      40 with 95%CI=4. 96-14. 23. The pooled OR with the random-effects model of pTNM
      and tumor grade in RASSF1A methylated patients, compared to unmethylated
      patients, was 0. 75 (95%CI=0. 28-1. 99) and 0. 39 (95%CI=0. 14-1. 09). This study
      showed that RASSF1A methylation appears to be an independent prognostic factor
      for bladder cancer. The present findings also require confirmation through
      adequately designed prospective studies.

PMID- 23139774
TI  - Methamphetamine reduces human influenza A virus replication.
AB  - Methamphetamine (meth) is a highly addictive psychostimulant that is among the
      most widely abused illicit drugs, with an estimated over 35 million users in the
      world. Several lines of evidence suggest that chronic meth abuse is a major
      factor for increased risk of infections with human immunodeficiency virus and
      possibly other pathogens, due to its immunosuppressive property. Influenza A
      virus infections frequently cause epidemics and pandemics of respiratory diseases
      among human populations. However, little is known about whether meth has the
      ability to enhance influenza A virus replication, thus increasing severity of
      influenza illness in meth abusers. Herein, we investigated the effects of meth on
      influenza A virus replication in human lung epithelial A549 cells. The cells were
      exposed to meth and infected with human influenza A/WSN/33 (H1N1) virus. The
      viral progenies were titrated by plaque assays, and the expression of viral
      proteins and cellular proteins involved in interferon responses was examined by
      Western blotting and immunofluorescence staining. We report the first evidence
      that meth significantly reduces, rather than increases, virus propagation and the
      susceptibility to influenza infection in the human lung epithelial cell line,
      consistent with a decrease in viral protein synthesis. These effects were
      apparently not caused by meth's effects on enhancing virus-induced interferon
      responses in the host cells, reducing viral biological activities, or reducing
      cell viability. Our results suggest that meth might not be a great risk factor
      for influenza A virus infection among meth abusers. Although the underlying
      mechanism responsible for the action of meth on attenuating virus replication
      requires further investigation, these findings prompt the study to examine
      whether other structurally similar compounds could be used as anti-influenza
      agents.

PMID- 23139775
TI  - Heterogeneity of the Stearoyl-CoA desaturase-1 (SCD1) gene and metabolic risk
      factors in the EPIC-Potsdam study.
AB  - BACKGROUND: Stearoyl-CoA desaturase-1 (SCD1) is an enzyme involved in lipid
      metabolism. In mice and humans its activity has been associated with traits of
      the metabolic syndrome, but also with the prevention of saturated fatty acids
      accumulation and subsequent inflammation, whereas for liver fat content
      inconsistent results have been reported. Thus, variants of the gene encoding SCD1
      (SCD1) could potentially modify metabolic risk factors, but few human studies
      have addressed this question. METHODS: In a sample of 2157 middle-aged men and
      women randomly drawn from the Potsdam cohort of the European Prospective
      Investigation into Cancer and Nutrition, we investigated the impact of 7 SCD1
      tagging-single nucleotide polymorphisms (rs1502593, rs522951, rs11190480, rs3071,
      rs3793767, rs10883463 and rs508384) and 5 inferred haplotypes with frequency >5%
      describing 90.9% of the genotype combinations in our population, on
      triglycerides, body mass index (BMI), waist circumference (WC), glycated
      haemoglobin (HbA1c), high-sensitivity C-reactive protein (hs-CRP), gamma
      glutamyltransferase (GGT), alanine aminotransferase (ALT) and fetuin-A. RESULTS:
      No significant associations between any of the SNPs or haplotypes and BMI, WC,
      fetuin-A and hs-CRP were observed. Associations of rs10883463 with triglycerides,
      GGT and HbA1c as well as of rs11190480 with ALT activity, were weak and became
      non-significant after multiple-testing correction. Also associations of the
      haplotype harbouring the minor allele of rs1502593 with HbA1c levels, the
      haplotype harbouring the minor alleles of rs11190480 and rs508384 with activity
      of ALT, and the haplotype harbouring the minor alleles of rs522951, rs10883463
      and rs508384 with triglyceride and HbA1C levels and GGT activities did not
      withstand multiple-testing correction. CONCLUSION: These findings suggest that
      there are no associations between common variants of SCD1 or its inferred
      haplotypes and the investigated metabolic risk factors. However, given the
      results from animal models, heterogeneity of human SCD1 warrants further
      investigation, in particular with regard to rare variants.

PMID- 23139776
TI  - Influenza virus A/Beijing/501/2009(H1N1) NS1 interacts with beta-tubulin and
      induces disruption of the microtubule network and apoptosis on A549 cells.
AB  - NS1 of influenza A virus is a key multifunctional protein that plays various
      roles in regulating viral replication mechanisms, host innate/adaptive immune
      responses, and cellular signalling pathways. These functions rely on its ability
      to participate in a multitude of protein-protein and protein-RNA interactions. To
      gain further insight into the role of NS1, a tandem affinity purification (TAP)
      method was utilized to find unknown interaction partner of NS1. The protein
      complexes of NS1 and its interacting partner were purified from A549 cell using
      TAP-tagged NS1 as bait, and co-purified cellular factors were identified by mass
      spectrometry (MS). We identified cellular beta-tubulin as a novel interaction
      partner of NS1. The RNA-binding domain of NS1 interacts with beta-tubulin through
      its RNA-binding domain, as judged by a glutathione S-transferase (GST) pull-down
      assay with the GST-fused functional domains of NS1. Immunofluorescence analysis
      further revealed that NS1 with beta-tubulin co-localized in the nucleus. In
      addition, the disruption of the microtubule network and apoptosis were also
      observed on NS1-transfected A549 cells. Our findings suggest that influenza A
      virus may utilize its NS1 protein to interact with cellular beta-tubulin to
      further disrupt normal cell division and induce apoptosis. Future work will
      illustrate whether this interaction is uniquely specific to the 2009 pandemic
      H1N1 virus.

PMID- 23139777
TI  - Reproducibility and relative validity of a food frequency questionnaire developed
      for adults in Taizhou, China.
AB  - OBJECTIVE: To evaluate the reproducibility and validity of a food frequency
      questionnaire (FFQ) developed to investigate the relationship between dietary
      factors and diseases in the adult Chinese population in East China. METHODS: A
      total of 78 males and 129 females aged 30-75 years completed four inconsecutive
      24-hour dietary recalls (24-HRs, served as a reference method) and two FFQs (FFQ1
      and FFQ2) over a nine-month interval. The reproducibility of the FFQ was
      estimated with correlation coefficients, cross-classification, and weighted kappa
      statistic. The validity was assessed by comparing the data obtained from FFQ and
      24-HRs. RESULTS: The median nutrient intakes assessed with FFQs were higher than
      the average of four 24-HRs. For the food groups, Spearman, Pearson, and
      intraclass correlation coefficients between FFQ1 and FFQ2 ranged from 0.23 to
      0.61, 0.27 to 0.64, and 0.26 to 0.65, respectively. For total energy and nutrient
      intakes, the corresponding coefficients ranged from 0.25 to 0.61, 0.28 to 0.64,
      and 0.28 to 0.62, respectively. The correlations between FFQ1 and FFQ2 for most
      nutrients decreased after adjustment with total energy intake. More than 70% of
      the subjects were classified into the same and adjacent categories by both FFQs.
      For food groups, the crude, energy-adjusted, and de-attenuated Spearman
      correlation coefficients between FFQ2 and the 24-HRs ranged from 0.17 to 0.59,
      0.10 to 0.57, and 0.11 to 0.64, respectively. For total energy and nutrient
      intakes, the corresponding coefficients ranged from 0.20 to 0.58, 0.08 to 0.54,
      and 0.09 to 0.56, respectively. More than 67% of the subjects were classified
      into the same and adjacent categories by both instruments. Both weighted kappa
      statistic and Bland-Altman Plots showed reasonably acceptable agreement between
      the FFQ2 and 24-HRs. CONCLUSION: The FFQ developed for adults in the Taizhou area
      is reasonably reliable and valid for assessment of most food and nutrient
      intakes.

PMID- 23139778
TI  - Comparison on virulence and immunogenicity of two recombinant vaccinia vaccines,
      Tian Tan and Guang9 strains, expressing the HIV-1 envelope gene.
AB  - BACKGROUND: The vaccinia virus Guang9 strain (VG9), derived from the vaccinia
      virus Tian Tan strain (VTT) has been found to be less virulent than VTT.
      METHODOLOGY/PRINCIPAL FINDINGS: To investigate whether VG9 could be a potential
      replicating virus vector, the TK genes in VG9 and VTT were replaced with the HIV
      1 envelope gene via homologous recombination, resulting in the recombinant
      viruses, VG9-E and VTT-E. The biology, virulence, humoral and cellular
      immunological responses of VG9-E and VTT-E were evaluated. Our results indicated
      no obvious difference in range of host cells and diffusion between two
      recombinant viruses. Neurovirulence for VG9-E in weanling and suckling mice, and
      skin virulence in rabbits, were lower than that of VTT-E. The humoral immune
      responses, including binding antibody and neutralizing antibody responses,
      induced by VG9-E were not significantly different from those for VTT-E whilst IFN
      gamma response which represented cellular immune response induced by VG9-E was
      significantly higher than that did by VTT-E. CONCLUSIONS/SIGNIFICANCE: Our
      results indicated that VG9-E was less virulent, yet induced higher cellular
      immune response than VTT-E. Therefore, it could be an ideal replicating vaccinia
      vector for HIV vaccine research and development.

PMID- 23139779
TI  - A 2nd generation linkage map of Heterobasidion annosum s.l. based on in silico
      anchoring of AFLP markers.
AB  - In this study, we present a 2(nd) generation genetic linkage map of a cross
      between the North American species Heterobasidion irregulare and H. occidentale,
      based on the alignment of the previously published 1(st) generation map to the
      parental genomes. We anchored 216 of the original 308 AFLP markers to their
      respective restriction sites using an in silico-approach. The map resolution was
      improved by adding 146 sequence-tagged microsatellite markers and 39 sequenced
      gene markers. The new markers confirmed the positions of the anchored AFLP
      markers, fused the original 39 linkage groups together into 17, and fully
      expanded 12 of these to single groups covering entire chromosomes. Map coverage
      of the genome increased from 55.3% to 92.8%, with 96.3% of 430 markers
      collinearly aligned with the genome sequence. The anchored map also improved the
      H. irregulare assembly considerably. It identified several errors in scaffold
      arrangements and assisted in reducing the total number of major scaffolds from 18
      to 15. This denser, more comprehensive map allowed sequence-based mapping of
      three intersterility loci and one mating type locus. This demonstrates the
      possibility to utilize an in silico procedure to convert anonymous markers into
      sequence-tagged ones, as well as the power of a sequence-anchored linkage map and
      its usefulness in the assembly of a whole genome sequence.

PMID- 23139780
TI  - Hyperglycemia-induced abnormalities in rat and human corneas: the potential of
      second harmonic generation microscopy.
AB  - BACKGROUND: Second Harmonic Generation (SHG) microscopy recently appeared as an
      efficient optical imaging technique to probe unstained collagen-rich tissues like
      cornea. Moreover, corneal remodeling occurs in many diseases and precise
      characterization requires overcoming the limitations of conventional techniques.
      In this work, we focus on diabetes, which affects hundreds of million people
      worldwide and most often leads to diabetic retinopathy, with no early diagnostic
      tool. This study then aims to establish the potential of SHG microscopy for in
      situ detection and characterization of hyperglycemia-induced abnormalities in the
      Descemet's membrane, in the posterior cornea. METHODOLOGY/PRINCIPAL FINDINGS: We
      studied corneas from age-matched control and Goto-Kakizaki rats, a spontaneous
      model of type 2 diabetes, and corneas from human donors with type 2 diabetes and
      without any diabetes. SHG imaging was compared to confocal microscopy, to
      histology characterization using conventional staining and transmitted light
      microscopy and to transmission electron microscopy. SHG imaging revealed collagen
      deposits in the Descemet's membrane of unstained corneas in a unique way compared
      to these gold standard techniques in ophthalmology. It provided background-free
      images of the three-dimensional interwoven distribution of the collagen deposits,
      with improved contrast compared to confocal microscopy. It also provided
      structural capability in intact corneas because of its high specificity to
      fibrillar collagen, with substantially larger field of view than transmission
      electron microscopy. Moreover, in vivo SHG imaging was demonstrated in Goto
      Kakizaki rats. CONCLUSIONS/SIGNIFICANCE: Our study shows unambiguously the high
      potential of SHG microscopy for three-dimensional characterization of structural
      abnormalities in unstained corneas. Furthermore, our demonstration of in vivo SHG
      imaging opens the way to long-term dynamical studies. This method should be
      easily generalized to other structural remodeling of the cornea and SHG
      microscopy should prove to be invaluable for in vivo corneal pathological
      studies.

PMID- 23139781
TI  - Proliferating cell nuclear antigen (PCNA) interactions in solution studied by
      NMR.
AB  - PCNA is an essential factor for DNA replication and repair. It forms a ring
      shaped structure of 86 kDa by the symmetric association of three identical
      protomers. The ring encircles the DNA and acts as a docking platform for other
      proteins, most of them containing the PCNA Interaction Protein sequence (PIP
      box). We have used NMR to characterize the interactions of PCNA with several
      other proteins and fragments in solution. The binding of the PIP-box peptide of
      the cell cycle inhibitor p21 to PCNA is consistent with the crystal structure of
      the complex. A shorter p21 peptide binds with reduced affinity but retains most
      of the molecular recognition determinants. However the binding of the
      corresponding peptide of the tumor suppressor ING1 is extremely weak, indicating
      that slight deviations from the consensus PIP-box sequence dramatically reduce
      the affinity for PCNA, in contrast with a proposed less stringent PIP-box
      sequence requirement. We could not detect any binding between PCNA and the MCL-1
      or the CDK2 protein, reported to interact with PCNA in biochemical assays. This
      suggests that they do not bind directly to PCNA, or they do but very weakly, with
      additional unidentified factors stabilizing the interactions in the cell.
      Backbone dynamics measurements show three PCNA regions with high relative
      flexibility, including the interdomain connector loop (IDCL) and the C-terminus,
      both of them involved in the interaction with the PIP-box. Our work provides the
      basis for high resolution studies of direct ligand binding to PCNA in solution.

PMID- 23139782
TI  - Effect of mistuning on the detection of a tone masked by a harmonic tone complex.
AB  - The human auditory system is sensitive in detecting "mistuned" components in a
      harmonic complex, which do not match the frequency pattern defined by the
      fundamental frequency of the complex. Depending on the frequency configuration,
      the mistuned component may be perceptually segregated from the complex and may be
      heard as a separate tone. In the context of a masking experiment, mistuning a
      single component decreases its masked threshold. In this study we propose to
      quantify the ability to detect a single component for fixed amounts of mistuning
      by adaptively varying its level. This method produces masking release by
      mistuning that can be compared to other masking release effects. Detection
      thresholds were obtained for various frequency configurations where the target
      component was resolved or unresolved in the auditory system. The results from 6
      normal-hearing listeners show a significant decrease of masked thresholds between
      harmonic and mistuned conditions in all configurations and provide evidence for
      the employment of different detection strategies for resolved and unresolved
      components. The data suggest that across-frequency processing is involved in the
      release from masking. The results emphasize the ability of this method to assess
      integrative aspects of pitch and harmonicity perception.

PMID- 23139783
TI  - Extreme levels of noise constitute a key neuromuscular deficit in the elderly.
AB  - Fluctuations during isometric force production tasks occur due to the inability
      of musculature to generate purely constant submaximal forces and are considered
      to be an estimation of neuromuscular noise. The human sensori-motor system
      regulates complex interactions between multiple afferent and efferent systems,
      which results in variability during functional task performance. Since muscles
      are the only active component of the motor system, it therefore seems reasonable
      that neuromuscular noise plays a key role in governing variability during both
      standing and walking. Seventy elderly women (including 34 fallers) performed
      multiple repetitions of isometric force production, quiet standing and walking
      tasks. No relationship between neuromuscular noise and functional task
      performance was observed in either the faller or the non-faller cohorts. When
      classified into groups with either nominal (group NOM, 25(th) -75(th) percentile)
      or extreme (either too high or too low, group EXT) levels of neuromuscular noise,
      group NOM demonstrated a clear association (r(2)>0.23, p<0.05) between
      neuromuscular noise and variability during task performance. On the other hand,
      group EXT demonstrated no such relationship, but also tended to walk slower, and
      had lower stride lengths, as well as lower isometric strength. These results
      suggest that neuromuscular noise is related to the quality of both static and
      dynamic functional task performance, but also that extreme levels of
      neuromuscular noise constitute a key neuromuscular deficit in the elderly.

PMID- 23139784
TI  - Can genetic estimators provide robust estimates of the effective number of
      breeders in small populations?
AB  - The effective population size (N(e)) is proportional to the loss of genetic
      diversity and the rate of inbreeding, and its accurate estimation is crucial for
      the monitoring of small populations. Here, we integrate temporal studies of the
      gecko Oedura reticulata, to compare genetic and demographic estimators of N(e).
      Because geckos have overlapping generations, our goal was to demographically
      estimate N(bI), the inbreeding effective number of breeders and to calculate the
      N(bI)/N(a) ratio (N(a) =number of adults) for four populations. Demographically
      estimated N(bI) ranged from 1 to 65 individuals. The mean reduction in the
      effective number of breeders relative to census size (N(bI)/N(a)) was 0.1 to 1.1.
      We identified the variance in reproductive success as the most important variable
      contributing to reduction of this ratio. We used four methods to estimate the
      genetic based inbreeding effective number of breeders N(bI(gen)) and the variance
      effective populations size N(eV(gen)) estimates from the genotype data. Two of
      these methods - a temporal moment-based (MBT) and a likelihood-based approach
      (TM3) require at least two samples in time, while the other two were single
      sample estimators - the linkage disequilibrium method with bias correction LDNe
      and the program ONeSAMP. The genetic based estimates were fairly similar across
      methods and also similar to the demographic estimates excluding those estimates,
      in which upper confidence interval boundaries were uninformative. For example,
      LDNe and ONeSAMP estimates ranged from 14-55 and 24-48 individuals, respectively.
      However, temporal methods suffered from a large variation in confidence intervals
      and concerns about the prior information. We conclude that the single-sample
      estimators are an acceptable short-cut to estimate N(bI) for species such as
      geckos and will be of great importance for the monitoring of species in
      fragmented landscapes.

PMID- 23139785
TI  - Maternal size and age shape offspring size in a live-bearing fish, Xiphophorus
      birchmanni.
AB  - Many studies of offspring size focus on differences in maternal investment that
      arise from ecological factors such as predation or competition. Classic theory
      predicts that these ecological factors will select for an optimal offspring size,
      and therefore that variation in a given environment will be minimized. Yet recent
      evidence suggests maternal traits such as size or age could also drive meaningful
      variation in offspring size. The generality of this pattern is unclear, as some
      studies suggest that it may represent non-adaptive variation or be an artifact of
      temporal or spatial differences in maternal environments. To clarify this
      pattern, we asked how maternal size, age and condition are related to each other
      in several populations of the swordtail Xiphophorus birchmanni. We then
      determined how these traits are related to offspring size, and whether they could
      resolve unexplained intra-population variation in this trait. We found that
      female size, age, and condition are correlated within populations; at some of
      these sites, older, larger females produce larger offspring than do younger
      females. The pattern was robust to differences among most, but not all, sites.
      Our results document a pattern that is consistent with recent theory predicting
      adaptive age- and size-dependence in maternal investment. Further work is needed
      to rule out non-adaptive explanations for this variation. Our results suggest
      that female size and age could play an under-appreciated role in population
      growth and evolution.

PMID- 23139786
TI  - Neuromelanins of human brain have soluble and insoluble components with dolichols
      attached to the melanic structure.
AB  - Neuromelanins (NMs) are neuronal pigments of melanic-lipidic type which
      accumulate during aging. They are involved in protective and degenerative
      mechanisms depending on the cellular context, however their structures are still
      poorly understood. NMs from nine human brain areas were analyzed in detail.
      Elemental analysis led to identification of three types of NM, while infrared
      spectroscopy showed that NMs from neurons of substantia nigra and locus
      coeruleus, which selectively degenerate in Parkinson's disease, have similar
      structure but different from NMs from brain regions not targeted by the disease.
      Synthetic melanins containing Fe and bovine serum albumin were prepared to model
      the natural product and help clarifying the structure of NMs. Extensive nuclear
      magnetic resonance spectroscopy studies showed the presence of dolichols both in
      the soluble and insoluble parts of NM. Diffusion measurements demonstrated that
      the dimethyl sulfoxide soluble components consist of oligomeric precursors with
      MWs in the range 1.4-52 kDa, while the insoluble part contains polymers of larger
      size but with a similar composition. These data suggest that the selective
      vulnerability of neurons of substantia nigra and locus coeruleus in Parkinson's
      disease might depend on the structure of the pigment. Moreover, they allow to
      propose a pathway for NM biosynthesis in human brain.

PMID- 23139788
TI  - The mammalian adult neurogenesis gene ontology (MANGO) provides a structural
      framework for published information on genes regulating adult hippocampal
      neurogenesis.
AB  - BACKGROUND: Adult hippocampal neurogenesis is not a single phenotype, but
      consists of a number of sub-processes, each of which is under complex genetic
      control. Interpretation of gene expression studies using existing resources often
      does not lead to results that address the interrelatedness of these processes.
      Formal structure, such as provided by ontologies, is essential in any field for
      comprehensive interpretation of existing knowledge but, until now, such a
      structure has been lacking for adult neurogenesis. METHODOLOGY/PRINCIPAL
      FINDINGS: We have created a resource with three components 1. A structured
      ontology describing the key stages in the development of adult hippocampal neural
      stem cells into functional granule cell neurons. 2. A comprehensive survey of the
      literature to annotate the results of all published reports on gene function in
      adult hippocampal neurogenesis (257 manuscripts covering 228 genes) to the
      appropriate terms in our ontology. 3. An easy-to-use searchable interface to the
      resulting database made freely available online. The manuscript presents an
      overview of the database highlighting global trends such as the current bias
      towards research on early proliferative stages, and an example gene set
      enrichment analysis. A limitation of the resource is the current scope of the
      literature which, however, is growing by around 100 publications per year. With
      the ontology and database in place, new findings can be rapidly annotated and
      regular updates of the database will be made publicly available.
      CONCLUSIONS/SIGNIFICANCE: The resource we present allows relevant interpretation
      of gene expression screens in terms of defined stages of postnatal neuronal
      development. Annotation of genes by hand from the adult neurogenesis literature
      ensures the data are directly applicable to the system under study. We believe
      this approach could also serve as an example to other fields in a 'bottom-up'
      community effort complementing the already successful 'top-down' approach of the
      Gene Ontology.

PMID- 23139787
TI  - Inhibition of hyaluronan synthesis reduces versican and fibronectin levels in
      trabecular meshwork cells.
AB  - Hyaluronan (HA) is a major component of the extracellular matrix (ECM) and is
      synthesized by three HA synthases (HAS). Similarities between the HAS2 knockout
      mouse and the hdf mutant mouse, which has a mutation in the versican gene,
      suggest that HA and versican expression may be linked. In this study, the
      relationship between HA synthesis and levels of versican, fibronectin and several
      other ECM components in trabecular meshwork cells from the anterior segment of
      the eye was investigated. HA synthesis was inhibited using 4-methylumbelliferone
      (4MU), or reduced by RNAi silencing of each individual HAS gene. Quantitative RT
      PCR and immunoblotting demonstrated a reduction in mRNA and protein levels of
      versican and fibronectin. Hyaluronidase treatment also reduced versican and
      fibronectin levels. These effects could not be reversed by addition of excess
      glucose or glucosamine or exogenous HA to the culture medium. CD44, tenascin C
      and fibrillin-1 mRNA levels were reduced by 4MU treatment, but SPARC and CSPG6
      mRNA levels were unaffected. Immunostaining of trabecular meshwork tissue after
      exposure to 4MU showed an altered localization pattern of HA-binding protein,
      versican and fibronectin. Reduction of versican by RNAi silencing did not affect
      HA concentration as assessed by ELISA. Together, these data imply that HA
      concentration affects synthesis of certain ECM components. Since precise
      regulation of the trabecular meshwork ECM composition and organization is
      required to maintain the aqueous humor outflow resistance and intraocular
      pressure homeostasis in the eye, coordinated coupling of HA levels and several of
      its ECM binding partners should facilitate this process.

PMID- 23139789
TI  - A heat-shock protein axis regulates VEGFR2 proteolysis, blood vessel development
      and repair.
AB  - Vascular endothelial growth factor A (VEGF-A) binds to the VEGFR2 receptor
      tyrosine kinase, regulating endothelial function, vascular physiology and
      angiogenesis. However, the mechanism underlying VEGFR2 turnover and degradation
      in this response is unclear. Here, we tested a role for heat-shock proteins in
      regulating the presentation of VEGFR2 to a degradative pathway. Pharmacological
      inhibition of HSP90 stimulated VEGFR2 degradation in primary endothelial cells
      and blocked VEGF-A-stimulated intracellular signaling via VEGFR2. HSP90
      inhibition stimulated the formation of a VEGFR2-HSP70 complex. Clathrin-mediated
      VEGFR2 endocytosis is required for this HSP-linked degradative pathway for
      targeting VEGFR2 to the endosome-lysosome system. HSP90 perturbation selectively
      inhibited VEGF-A-stimulated human endothelial cell migration in vitro. A mouse
      femoral artery model showed that HSP90 inhibition also blocked blood vessel
      repair in vivo consistent with decreased endothelial regeneration. Depletion of
      either HSP70 or HSP90 caused defects in blood vessel formation in a transgenic
      zebrafish model. We conclude that perturbation of the HSP70-HSP90 heat-shock
      protein axis stimulates degradation of endothelial VEGFR2 and modulates VEGF-A
      stimulated intracellular signaling, endothelial cell migration, blood vessel
      development and repair.

PMID- 23139790
TI  - Xanthurenic acid binds to neuronal G-protein-coupled receptors that secondarily
      activate cationic channels in the cell line NCB-20.
AB  - Xanthurenic acid (XA) is a metabolite of the tryptophan oxidation pathway through
      kynurenine and 3-hydroxykynurenine. XA was until now considered as a
      detoxification compound and dead-end product reducing accumulation of reactive
      radical species. Apart from a specific role for XA in the signaling cascade
      resulting in gamete maturation in mosquitoes, nothing was known about its
      functions in other species including mammals. Based upon XA distribution,
      transport, accumulation and release in the rat brain, we have recently suggested
      that XA may potentially be involved in neurotransmission/neuromodulation,
      assuming that neurons presumably express specific XA receptors. Recently, it has
      been shown that XA could act as a positive allosteric ligand for class II
      metabotropic glutamate receptors. This finding reinforces the proposed signaling
      role of XA in brain. Our present results provide several lines of evidence in
      favor of the existence of specific receptors for XA in the brain. First, binding
      experiments combined with autoradiography and time-course analysis led to the
      characterization of XA binding sites in the rat brain. Second, specific kinetic
      and pharmacological properties exhibited by these binding sites are in favor of G
      protein-coupled receptors (GPCR). Finally, in patch-clamp and calcium imaging
      experiments using NCB-20 cells that do not express glutamate-induced calcium
      signals, XA elicited specific responses involving activation of cationic channels
      and increases in intracellular Ca(2+) concentration. Altogether, these results
      suggest that XA, acting through a GPCR-induced cationic channel modulatory
      mechanism, may exert excitatory functions in various brain neuronal pathways.

PMID- 23139791
TI  - Gene expression in the spinal cord in female lewis rats with experimental
      autoimmune encephalomyelitis induced with myelin basic protein.
AB  - BACKGROUND: Experimental autoimmune encephalomyelitis (EAE), the best available
      model of multiple sclerosis, can be induced in different animal strains using
      immunization with central nervous system antigens. EAE is associated with
      inflammation and demyelination of the nervous system. Micro-array can be used to
      investigate gene expression and biological pathways that are altered during
      disease. There are few studies of the changes in gene expression in EAE, and
      these have mostly been done in a chronic mouse EAE model. EAE induced in the
      Lewis with myelin basic protein (MBP-EAE) is well characterised, making it an
      ideal candidate for the analysis of gene expression in this disease model.
      METHODOLOGY/PRINCIPAL FINDINGS: MBP-EAE was induced in female Lewis rats by
      inoculation with MBP and adjuvants. Total RNA was extracted from the spinal cords
      and used for micro-array analysis using AffimetrixGeneChip Rat Exon 1.0 ST
      Arrays. Gene expression in the spinal cords was compared between healthy female
      rats and female rats with MBP-EAE. Gene expression in the spinal cord of rats
      with MBP-EAE differed from that in the spinal cord of normal rats, and there was
      regulation of pathways involved with immune function and nervous system function.
      For selected genes the change in expression was confirmed with real-time PCR.
      CONCLUSIONS/SIGNIFICANCE: EAE leads to modulation of gene expression in the
      spinal cord. We have identified the genes that are most significantly regulated
      in MBP-EAE in the Lewis rat and produced a profile of gene expression in the
      spinal cord at the peak of disease.

PMID- 23139792
TI  - A new cell-selective three-dimensional microincubator based on silicon photonic
      crystals.
AB  - In this work, we show that vertical, high aspect-ratio (HAR) photonic crystals
      (PhCs), consisting of periodic arrays of 5 um wide gaps with depth of 50 um
      separated by 3 um thick silicon walls, fabricated by electrochemical
      micromachining, can be used as three-dimensional microincubators, allowing cell
      lines to be selectively grown into the gaps. Silicon micromachined dice
      incorporating regions with different surface profiles, namely flat silicon and
      deeply etched PhC, were used as microincubators for culturing adherent cell lines
      with different morphology and adhesion properties. We extensively investigated
      and compared the proliferative behavior on HAR PhCs of eight human cell models,
      with different origins, such as the epithelial (SW613-B3; HeLa; SW480; HCT116;
      HT29) and the mesenchymal (MRC-5V1; CF; HT1080). We also verified the
      contribution of cell sedimentation into the silicon gaps. Fluorescence microscopy
      analysis highlights that only cell lines that exhibit, in the tested culture
      condition, the behavior typical of the mesenchymal phenotype are able to
      penetrate into the gaps of the PhC, extending their body deeply in the narrow
      gaps between adjacent silicon walls, and to grow adherent to the vertical
      surfaces of silicon. Results reported in this work, confirmed in various
      experiments, strongly support our statement that such three-dimensional
      microstructures have selection capabilities with regard to the cell lines that
      can actively populate the narrow gaps. Cells with a mesenchymal phenotype could
      be exploited in the next future as bioreceptors, in combination with HAR PhC
      optical transducers, e.g., for label-free optical detection of cellular
      activities involving changes in cell adhesion and/or morphology (e.g., apoptosis)
      in a three-dimensional microenvironment.

PMID- 23139793
TI  - Detection of bacterial 16S rRNA and identification of four clinically important
      bacteria by real-time PCR.
AB  - Within the paradigm of clinical infectious disease research, Acinetobacter
      baumannii, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa
      represent the four most clinically relevant, and hence most extensively studied
      bacteria. Current culture-based methods for identifying these organisms are slow
      and cumbersome, and there is increasing need for more rapid and accurate
      molecular detection methods. Using bioinformatic tools, 962,279 bacterial 16S
      rRNA gene sequences were aligned, and regions of homology were selected to
      generate a set of real-time PCR primers that target 93.6% of all bacterial 16S
      rRNA sequences published to date. A set of four species-specific real-time PCR
      primer pairs were also designed, capable of detecting less than 100 genome copies
      of A. baumannii, E. coli, K. pneumoniae, and P. aeruginosa. All primers were
      tested for specificity in vitro against 50 species of Gram-positive and -negative
      bacteria. Additionally, the species-specific primers were tested against a panel
      of 200 clinical isolates of each species, randomly selected from a large
      repository of clinical isolates from diverse areas and sources. A comparison of
      culture and real-time PCR demonstrated 100% concordance. The primers were
      incorporated into a rapid assay capable of positive identification from plate or
      broth cultures in less than 90 minutes. Furthermore, our data demonstrate that
      current targets, such as the uidA gene in E.coli, are not suitable as species
      specific genes due to sequence variation. The assay described herein is rapid,
      cost-effective and accurate, and can be easily incorporated into any research
      laboratory capable of real-time PCR.

PMID- 23139794
TI  - Molecular storage of ozone in a clathrate hydrate: an attempt at preserving ozone
      at high concentrations.
AB  - This paper reports an experimental study of the formation of a mixed O(3)+ O(2)+
      CO(2) hydrate and its frozen storage under atmospheric pressure, which aimed to
      establish a hydrate-based technology for preserving ozone (O(3)), a chemically
      unstable substance, for various industrial, medical and consumer uses. By
      improving the experimental technique that we recently devised for forming an
      O(3)+ O(2)+ CO(2) hydrate, we succeeded in significantly increasing the fraction
      of ozone contained in the hydrate. For a hydrate formed at a system pressure of
      3.0 MPa, the mass fraction of ozone was initially about 0.9%; and even after a 20
      day storage at -25 degrees C and atmospheric pressure, it was still about 0.6%.
      These results support the prospect of establishing an economical, safe, and easy
      to-handle ozone-preservation technology of practical use.

PMID- 23139795
TI  - Subterranean sympatry: an investigation into diet using stable isotope analysis.
AB  - In the Western Cape three species of mole-rat occur in sympatry, however, little
      is known about differences in their dietary preferences. Dietary composition of
      the three species; the common mole-rat (Cryptomys hottentotus hottentotus), the
      Cape mole-rat (Georychus capensis) and the Cape dune mole-rat (Bathyergus
      suillus) were examined using stable isotope analysis. Blood, fur and claw samples
      were collected from 70 mole-rats, in addition to several potential food items, to
      assess food selection of the three species under natural conditions. Overall
      there was a significant difference in the isotopic composition (delta(13)C and
      delta(15)N) between all three species and significant differences in their diet
      composition. There were also significant differences between tissues in all three
      species suggesting temporal variation in diet. The small size and colonial
      lifestyle of C. h. hottentotus allows it to feed almost 100% on bulbs, while the
      solitary and larger species G. capensis and B. suillus fed to a greater extent on
      other resources such as grasses and clover. B. suillus, the largest of the
      species, had the most generalized diet. However, overall all species relied most
      heavily upon geophytes and consumed the same species suggesting competition for
      resources could exist. We also showed a high level of individual variation in
      diet choices. This was most pronounced in B. suillus and G. capensis and less so
      in C. h. hottentotus. We demonstrate that stable isotope analysis can
      successfully be applied to examine dietary patterns in subterranean mammals and
      provide insights into foraging patterns and dietary variation at both the inter
      and intra population level.

PMID- 23139796
TI  - MitoQ blunts mitochondrial and renal damage during cold preservation of porcine
      kidneys.
AB  - Cold preservation has greatly facilitated the use of cadaveric kidneys for
      transplantation but damage occurs during the preservation episode. It is well
      established that oxidant production increases during cold renal preservation and
      mitochondria are a key target for injury. Our laboratory has demonstrated that
      cold storage of renal cells and rat kidneys leads to increased mitochondrial
      superoxide levels and mitochondrial electron transport chain damage, and that
      addition of Mitoquinone (MitoQ) to the preservation solutions blunted this
      injury. In order to better translate animal studies, the inclusion of large
      animal models is necessary to develop safe preclinical protocols. Therefore, we
      tested the hypothesis that addition of MitoQ to cold storage solution preserves
      mitochondrial function by decreasing oxidative stress, leading to less renal
      tubular damage during cold preservation of porcine kidneys employing a standard
      criteria donor model. Results showed that cold storage significantly induced
      oxidative stress (nitrotyrosine), renal tubular damage, and cell death. Using
      High Resolution Respirometry and fresh porcine kidney biopsies to assess
      mitochondrial function we showed that MitoQ significantly improved complex II/III
      respiration of the electron transport chain following 24 hours of cold storage.
      In addition, MitoQ blunted oxidative stress, renal tubular damage, and cell death
      after 48 hours. These results suggested that MitoQ decreased oxidative stress,
      tubular damage and cell death by improving mitochondrial function during cold
      storage. Therefore this compound should be considered as an integral part of
      organ preservation solution prior to transplantation.

PMID- 23139797
TI  - HLA-DRB1 alleles are associated with the susceptibility to sporadic Parkinson's
      disease in Chinese Han population.
AB  - Immune disorders may play an important role in the pathogenesis of Parkinson's
      disease (PD). Recently, polymorphisms in the HLA-DR region have been found to be
      associated with sporadic PD in European ancestry populations. However,
      polymorphisms in the HLA complex are highly variable with ethnic and geographic
      origin. To explore the relationships between polymorphisms of the HLA-DR region
      and sporadic PD in Chinese Han population, we genotyped 567 sporadic PD patients
      and 746 healthy controls in two independent series for the HLA-DRB1 locus with
      Polymerase chain reaction-sequence based typing(PCR-SBT). The chi(2) test was
      used to evaluate the distribution of allele frequencies between the patients and
      healthy controls. The impact of HLA-DRB1 alleles on PD risk was estimated by
      unconditional logistic regression. We found a significant higher frequency of HLA
      DRB1*0301 in sporadic PD patients than in healthy controls and a positive
      association, which was independent of onset age, between HLA-DRB1*0301 and PD
      risk. Conversely, a lower frequency of HLA-DRB1*0406 was found in sporadic PD
      patients than in healthy controls, with a negative association between HLA
      DRB1*0406 and PD risk. Furthermore, a meta-analysis involving 195205 individuals
      was conducted to summarize the frequencies of these two alleles in populations
      from various ethnic regions, we found a higher frequency of HLA-DRB1*0301, but a
      lower frequency of HLA-DRB1*0406 in European ancestry populations than that in
      Asians, this was consistent with the higher prevalence of sporadic PD in European
      ancestry populations. Based on these results, we speculate that HLA-DRB1 alleles
      are associated with the susceptibility to sporadic PD in Chinese Han population,
      among them HLA-DRB1*0301 is a risk allele while the effect of HLA-DRB1*0406
      deserves debate.

PMID- 23139798
TI  - Sub-inhibitory cefsulodin sensitization of E. coli to beta-lactams is mediated by
      PBP1b inhibition.
AB  - The combination of antibiotics is one of the strategies to combat drug-resistant
      bacteria, though only a handful of such combinations are in use, such as the beta
      lactam combinations. In the present study, the efficacy of a specific sub
      inhibitory concentration of cefsulodin with other beta-lactams was evaluated
      against a range of Gram-negative clinical isolates. This approach increased the
      sensitivity of the isolates, regardless of the beta-lactamase production. The
      preferred target and mechanism of action of cefsulodin were identified in
      laboratory strains of Escherichia coli, by examining the effects of deleting the
      penicillin-binding protein (PBP) 1a and 1b encoding genes individually. Deletion
      of PBP1b was involved in sensitizing the bacteria to beta-lactam agents,
      irrespective of its O-antigen status. Moreover, the use of a sub-inhibitory
      concentration of cefsulodin in combination with a beta-lactam exerted an effect
      similar to that one obtained for PBP1b gene deletion. We conclude that the
      identified beta-lactam/cefsulodin combination works by inhibiting PBP1b (at least
      partially) despite the involvement of beta-lactamases, and therefore could be
      extended to a broad range of Gram-negative pathogens.

PMID- 23139799
TI  - Impact of Xpert MTB/RIF testing on tuberculosis management and outcomes in
      hospitalized patients in Uganda.
AB  - RATIONALE: The clinical impact of Xpert MTB/RIF for tuberculosis (TB) diagnosis
      in high HIV-prevalence settings is unknown. OBJECTIVE: To determine the
      diagnostic accuracy and impact of Xpert MTB/RIF among high-risk TB suspects.
      METHODS: WE PROSPECTIVELY ENROLLED CONSECUTIVE, HOSPITALIZED, UGANDAN TB SUSPECTS
      IN TWO PHASES: baseline phase in which Xpert MTB/RIF results were not reported to
      clinicians and an implementation phase in which results were reported. We
      determined the diagnostic accuracy of Xpert MTB/RIF in reference to culture
      (solid and liquid) and compared patient outcomes by study phase. RESULTS: 477
      patients were included (baseline phase 287, implementation phase 190). Xpert
      MTB/RIF had high sensitivity (187/237, 79%, 95% CI: 73-84%) and specificity
      (190/199, 96%, 95% CI: 92-98%) for culture-positive TB overall, but sensitivity
      was lower (34/81, 42%, 95% CI: 31-54%) among smear-negative TB cases. Xpert
      MTB/RIF reduced median days-to-TB detection for all TB cases (1 [IQR 0-26] vs. 0
      [IQR 0-1], p<0.001), and for smear-negative TB (35 [IQR 22-55] vs. 22 [IQR 0-33],
      p=0.001). However, median days-to-TB treatment was similar for all TB cases (1
      [IQR 0-5] vs. 0 [IQR 0-2], p=0.06) and for smear-negative TB (7 [IQR 3-53] vs. 6
      [IQR 1-61], p=0.78). Two-month mortality was also similar between study phases
      among 252 TB cases (17% vs. 14%, difference +3%, 95% CI: -21% to +27%, p=0.80),
      and among 87 smear-negative TB cases (28% vs. 22%, difference +6%, 95% CI: -34 to
      +46%, p=0.77). CONCLUSIONS: Xpert MTB/RIF facilitated more accurate and earlier
      TB diagnosis, leading to a higher proportion of TB suspects with a confirmed TB
      diagnosis prior to hospital discharge in a high HIV/low MDR TB prevalence
      setting. However, our study did not detect a decrease in two-month mortality
      following implementation of Xpert MTB/RIF possibly because of insufficient
      powering, differences in empiric TB treatment rates, and disease severity between
      study phases.

PMID- 23139800
TI  - FABP4 dynamics in obesity: discrepancies in adipose tissue and liver expression
      regarding circulating plasma levels.
AB  - BACKGROUND: FABP4 is predominantly expressed in adipose tissue, and its
      circulating levels are linked with obesity and a poor atherogenic profile.
      OBJECTIVE: In patients with a wide BMI range, we analyze FABP4 expression in
      adipose and hepatic tissues in the settings of obesity and insulin resistance.
      Associations between FABP4 expression in adipose tissue and the FABP4 plasma
      level as well as the main adipogenic and lipolytic genes expressed in adipose
      tissue were also analyzed. METHODS: The expression of several lipogenic,
      lipolytic, PPAR family and FABP family genes was analyzed by real time PCR. FABP4
      protein expression in total adipose tissues and its fractions were determined by
      western blot. RESULTS: In obesity FABP4 expression was down-regulated (at both
      mRNA and protein levels), with its levels mainly predicted by ATGL and inversely
      by the HOMA-IR index. The BMI appeared as the only determinant of the FABP4
      variation in both adipose tissue depots. FABP4 plasma levels showed a significant
      progressive increase according to BMI but no association was detected between
      FABP4 circulating levels and SAT or VAT FABP4 gene expression. The gene
      expression of FABP1, FABP4 and FABP5 in hepatic tissue was significantly higher
      in tissue from the obese IR patients compared to the non-IR group. CONCLUSION:
      The inverse pattern in FABP4 expression between adipose and hepatic tissue
      observed in morbid obese patients, regarding the IR context, suggests that both
      tissues may act in a balanced manner. These differences may help us to understand
      the discrepancies between circulating plasma levels and adipose tissue expression
      in obesity.

PMID- 23139801
TI  - Prediction of altered 3'- UTR miRNA-binding sites from RNA-Seq data: the swine
      leukocyte antigen complex (SLA) as a model region.
AB  - THE SLA (swine leukocyte antigen, MHC: SLA) genes are the most important
      determinants of immune, infectious disease and vaccine response in pigs; several
      genetic associations with immunity and swine production traits have been
      reported. However, most of the current knowledge on SLA is limited to gene coding
      regions. MicroRNAs (miRNAs) are small molecules that post-transcriptionally
      regulate the expression of a large number of protein-coding genes in metazoans,
      and are suggested to play important roles in fine-tuning immune mechanisms and
      disease responses. Polymorphisms in either miRNAs or their gene targets may have
      a significant impact on gene expression by abolishing, weakening or creating
      miRNA target sites, possibly leading to phenotypic variation. We explored the
      impact of variants in the 3'-UTR miRNA target sites of genes within the whole SLA
      region. The combined predictions by TargetScan, PACMIT and TargetSpy, based on
      different biological parameters, empowered the identification of miRNA target
      sites and the discovery of polymorphic miRNA target sites (poly-miRTSs).
      Predictions for three SLA genes characterized by a different range of sequence
      variation provided proof of principle for the analysis of poly-miRTSs from a
      total of 144 M RNA-Seq reads collected from different porcine tissues. Twenty
      four novel SNPs were predicted to affect miRNA-binding sites in 19 genes of the
      SLA region. Seven of these genes (SLA-1, SLA-6, SLA-DQA, SLA-DQB1, SLA-DOA, SLA
      DOB and TAP1) are linked to antigen processing and presentation functions, which
      is reminiscent of associations with disease traits reported for altered miRNA
      binding to MHC genes in humans. An inverse correlation in expression levels was
      demonstrated between miRNAs and co-expressed SLA targets by exploiting a
      published dataset (RNA-Seq and small RNA-Seq) of three porcine tissues. Our
      results support the resource value of RNA-Seq collections to identify SNPs that
      may lead to altered miRNA regulation patterns.

PMID- 23139802
TI  - Incidence and epidemiology of hospitalized influenza cases in rural Thailand
      during the influenza A (H1N1)pdm09 pandemic, 2009-2010.
AB  - BACKGROUND: Data on the burden of the 2009 influenza pandemic in Asia are
      limited. Influenza A(H1N1)pdm09 was first reported in Thailand in May 2009. We
      assessed incidence and epidemiology of influenza-associated hospitalizations
      during 2009-2010. METHODS: We conducted active, population-based surveillance for
      hospitalized cases of acute lower respiratory infection (ALRI) in all 20
      hospitals in two rural provinces. ALRI patients were sampled 1?2 for
      participation in an etiology study in which nasopharyngeal swabs were collected
      for influenza virus testing by PCR. RESULTS: Of 7,207 patients tested, 902
      (12.5%) were influenza-positive, including 190 (7.8%) of 2,436 children aged <5
      years; 86% were influenza A virus (46% A(H1N1)pdm09, 30% H3N2, 6.5% H1N1, 3.5%
      not subtyped) and 13% were influenza B virus. Cases of influenza A(H1N1)pdm09
      first peaked in August 2009 when 17% of tested patients were positive. Subsequent
      peaks during 2009 and 2010 represented a mix of influenza A(H1N1)pdm09, H3N2, and
      influenza B viruses. The estimated annual incidence of hospitalized influenza
      cases was 136 per 100,000, highest in ages <5 years (477 per 100,000) and >75
      years (407 per 100,000). The incidence of influenza A(H1N1)pdm09 was 62 per
      100,000 (214 per 100,000 in children <5 years). Eleven influenza-infected
      patients required mechanical ventilation, and four patients died, all adults with
      influenza A(H1N1)pdm09 (1) or H3N2 (3). CONCLUSIONS: Influenza-associated
      hospitalization rates in Thailand during 2009-10 were substantial and exceeded
      rates described in western countries. Influenza A(H1N1)pdm09 predominated, but
      H3N2 also caused notable morbidity. Expanded influenza vaccination coverage could
      have considerable public health impact, especially in young children.

PMID- 23139803
TI  - c-Jun amino-terminal kinase-1 mediates glucose-responsive upregulation of the RNA
      editing enzyme ADAR2 in pancreatic beta-cells.
AB  - A-to-I RNA editing catalyzed by the two main members of the adenosine deaminase
      acting on RNA (ADAR) family, ADAR1 and ADAR2, represents a RNA-based recoding
      mechanism implicated in a variety of cellular processes. Previously we have
      demonstrated that the expression of ADAR2 in pancreatic islet beta-cells is
      responsive to the metabolic cues and ADAR2 deficiency affects regulated cellular
      exocytosis. To investigate the molecular mechanism by which ADAR2 is
      metabolically regulated, we found that in cultured beta-cells and primary islets,
      the stress-activated protein kinase JNK1 mediates the upregulation of ADAR2 in
      response to changes of the nutritional state. In parallel with glucose induction
      of ADAR2 expression, JNK phosphorylation was concurrently increased in insulin
      secreting INS-1 beta-cells. Pharmacological inhibition of JNKs or siRNA knockdown
      of the expression of JNK1 prominently suppressed glucose-augmented ADAR2
      expression, resulting in decreased efficiency of ADAR2 auto-editing.
      Consistently, the mRNA expression of Adar2 was selectively reduced in the islets
      from JNK1 null mice in comparison with that of wild-type littermates or JNK2 null
      mice, and ablation of JNK1 diminished high-fat diet-induced Adar2 expression in
      the islets from JNK1 null mice. Furthermore, promoter analysis of the mouse Adar2
      gene identified a glucose-responsive region and revealed the transcription factor
      c-Jun as a driver of Adar2 transcription. Taken together, these results
      demonstrate that JNK1 serves as a crucial component in mediating glucose
      responsive upregulation of ADAR2 expression in pancreatic beta-cells. Thus, the
      JNK1 pathway may be functionally linked to the nutrient-sensing actions of ADAR2
      mediated RNA editing in professional secretory cells.

PMID- 23139804
TI  - Cellulase linkers are optimized based on domain type and function: insights from
      sequence analysis, biophysical measurements, and molecular simulation.
AB  - Cellulase enzymes deconstruct cellulose to glucose, and are often comprised of
      glycosylated linkers connecting glycoside hydrolases (GHs) to carbohydrate
      binding modules (CBMs). Although linker modifications can alter cellulase
      activity, the functional role of linkers beyond domain connectivity remains
      unknown. Here we investigate cellulase linkers connecting GH Family 6 or 7
      catalytic domains to Family 1 or 2 CBMs, from both bacterial and eukaryotic
      cellulases to identify conserved characteristics potentially related to function.
      Sequence analysis suggests that the linker lengths between structured domains are
      optimized based on the GH domain and CBM type, such that linker length may be
      important for activity. Longer linkers are observed in eukaryotic GH Family 6
      cellulases compared to GH Family 7 cellulases. Bacterial GH Family 6 cellulases
      are found with structured domains in either N to C terminal order, and similar
      linker lengths suggest there is no effect of domain order on length. O
      glycosylation is uniformly distributed across linkers, suggesting that glycans
      are required along entire linker lengths for proteolysis protection and, as
      suggested by simulation, for extension. Sequence comparisons show that proline
      content for bacterial linkers is more than double that observed in eukaryotic
      linkers, but with fewer putative O-glycan sites, suggesting alternative methods
      for extension. Conversely, near linker termini where linkers connect to
      structured domains, O-glycosylation sites are observed less frequently, whereas
      glycines are more prevalent, suggesting the need for flexibility to achieve
      proper domain orientations. Putative N-glycosylation sites are quite rare in
      cellulase linkers, while an N-P motif, which strongly disfavors the attachment of
      N-glycans, is commonly observed. These results suggest that linkers exhibit
      features that are likely tailored for optimal function, despite possessing low
      sequence identity. This study suggests that cellulase linkers may exhibit
      function in enzyme action, and highlights the need for additional studies to
      elucidate cellulase linker functions.

PMID- 23139805
TI  - Library preparation and multiplex capture for massive parallel sequencing
      applications made efficient and easy.
AB  - During the recent years, rapid development of sequencing technologies and a
      competitive market has enabled researchers to perform massive sequencing projects
      at a reasonable cost. As the price for the actual sequencing reactions drops,
      enabling more samples to be sequenced, the relative price for preparing libraries
      gets larger and the practical laboratory work becomes complex and tedious. We
      present a cost-effective strategy for simplified library preparation compatible
      with both whole genome- and targeted sequencing experiments. An optimized enzyme
      composition and reaction buffer reduces the number of required clean-up steps and
      allows for usage of bulk enzymes which makes the whole process cheap, efficient
      and simple. We also present a two-tagging strategy, which allows for multiplex
      sequencing of targeted regions. To prove our concept, we have prepared libraries
      for low-pass sequencing from 100 ng DNA, performed 2-, 4- and 8-plex exome
      capture and a 96-plex capture of a 500 kb region. In all samples we see a high
      concordance (>99.4%) of SNP calls when comparing to commercially available SNP
      chip platforms.

PMID- 23139806
TI  - Individual differences in the discrimination of novel speech sounds: effects of
      sex, temporal processing, musical and cognitive abilities.
AB  - This study examined whether rapid temporal auditory processing, verbal working
      memory capacity, non-verbal intelligence, executive functioning, musical ability
      and prior foreign language experience predicted how well native English speakers
      (N=120) discriminated Norwegian tonal and vowel contrasts as well as a non-speech
      analogue of the tonal contrast and a native vowel contrast presented over noise.
      Results confirmed a male advantage for temporal and tonal processing, and also
      revealed that temporal processing was associated with both non-verbal
      intelligence and speech processing. In contrast, effects of musical ability on
      non-native speech-sound processing and of inhibitory control on vowel
      discrimination were not mediated by temporal processing. These results suggest
      that individual differences in non-native speech-sound processing are to some
      extent determined by temporal auditory processing ability, in which males perform
      better, but are also determined by a host of other abilities that are deployed
      flexibly depending on the characteristics of the target sounds.

PMID- 23139807
TI  - Putative monofunctional type I polyketide synthase units: a dinoflagellate
      specific feature?
AB  - Marine dinoflagellates (alveolata) are microalgae of which some cause harmful
      algal blooms and produce a broad variety of most likely polyketide synthesis
      derived phycotoxins. Recently, novel polyketide synthesase (PKS) transcripts have
      been described from the Florida red tide dinoflagellate Karenia brevis
      (gymnodiniales) which are evolutionarily related to Type I PKS but were
      apparently expressed as monofunctional proteins, a feature typical of Type II
      PKS. Here, we investigated expression units of PKS I-like sequences in
      Alexandrium ostenfeldii (gonyaulacales) and Heterocapsa triquetra (peridiniales)
      at the transcript and protein level. The five full length transcripts we obtained
      were all characterized by polyadenylation, a 3' UTR and the dinoflagellate
      specific spliced leader sequence at the 5'end. Each of the five transcripts
      encoded a single ketoacylsynthase (KS) domain showing high similarity to K.
      brevis KS sequences. The monofunctional structure was also confirmed using
      dinoflagellate specific KS antibodies in Western Blots. In a maximum likelihood
      phylogenetic analysis of KS domains from diverse PKSs, dinoflagellate KSs formed
      a clade placed well within the protist Type I PKS clade between apicomplexa,
      haptophytes and chlorophytes. These findings indicate that the atypical PKS I
      structure, i.e., expression as putative monofunctional units, might be a
      dinoflagellate specific feature. In addition, the sequenced transcripts harbored
      a previously unknown, apparently dinoflagellate specific conserved N-terminal
      domain. We discuss the implications of this novel region with regard to the
      putative monofunctional organization of Type I PKS in dinoflagellates.

PMID- 23139808
TI  - Motion noise changes directional interaction between transparently moving stimuli
      from repulsion to attraction.
AB  - To interpret visual scenes, visual systems need to segment or integrate multiple
      moving features into distinct objects or surfaces. Previous studies have found
      that the perceived direction separation between two transparently moving random
      dot stimuli is wider than the actual direction separation. This perceptual
      "direction repulsion" is useful for segmenting overlapping motion vectors. Here
      we investigate the effects of motion noise on the directional interaction between
      overlapping moving stimuli. Human subjects viewed two overlapping random-dot
      patches moving in different directions and judged the direction separation
      between the two motion vectors. We found that the perceived direction separation
      progressively changed from wide to narrow as the level of motion noise in the
      stimuli was increased, showing a switch from direction repulsion to attraction
      (i.e. smaller than the veridical direction separation). We also found that
      direction attraction occurred at a wider range of direction separations than
      direction repulsion. The normalized effects of both direction repulsion and
      attraction were the strongest near the direction separation of ~25 degrees  and
      declined as the direction separation further increased. These results support the
      idea that motion noise prompts motion integration to overcome stimulus ambiguity.
      Our findings provide new constraints on neural models of motion transparency and
      segmentation.

PMID- 23139809
TI  - Evidence for vocal learning and limited dispersal as dual mechanisms for dialect
      maintenance in a parrot.
AB  - Studies of avian vocal dialects commonly find evidence of geographic and acoustic
      stability in the face of substantial gene flow between dialects. The vocal
      imitation and reduced dispersal hypotheses are alternatives to explain this
      mismatch between vocal and genetic variation. We experimentally simulated
      dispersal in the yellow-naped amazon (Amazona auropalliata) by moving individuals
      within and across dialect boundaries in Costa Rica. One juvenile translocated
      across dialect boundaries altered its contact call to imitate the acoustic form
      of the local call six weeks post-release. In contrast, four adults translocated
      across dialect boundaries returned to their original capture site within 120
      days, while five cross-dialect translocated adults who remained at the release
      site did not alter their contact calls. Translocated individuals were observed to
      show some segregation from resident flocks. The observation of vocal imitation by
      the juvenile bird supports the vocal imitation, whereas the behavior of adults is
      more consistent with the reduced dispersal hypotheses. Taken together, our
      results suggest that both post-dispersal learning by juveniles and high
      philopatry in adults could explain the stability of vocal dialects in the face of
      immigration and gene flow.

PMID- 23139810
TI  - Towards optimising the production of and expression from polycistronic vectors in
      embryonic stem cells.
AB  - Polycistronic vectors linked by self-processing 2A peptides have been
      successfully used in cellular reprogramming. The expression of these vectors has
      yet to be well documented in embryonic stem cells. In the present study, we
      generated expression cassettes containing combinatorial arrangements of 3
      pancreatic transcriptions factors (Pdx1, Nkx2.2 and Ngn3) together with an eGFP
      reporter, all linked by self-processing 2A peptides. The study tested the utility
      of constructing complex expression cassettes by ligating multiple components,
      each flanked by unique restriction sites. This approach allowed flexible and
      efficient design and construction of a combinatorial array of polycistronic
      constructs, which were expressed after transient transfection into embryonic stem
      cells. The inclusion of EGFP provided for a convenient proxy measure of
      expression and showed that expression was similar regardless of EGFP's position
      within a 2A polycistronic construct. Expression of terminal EGFP was 51% and 24%
      more efficient when linked by T2A compared to F2A or E2A peptides, respectively.
      The highest level of expression was achieved when all genes in a construct were
      linked exclusively by T2A peptides. This effect of T2A was independent of the
      type of promoter used, as a similar increase in terminal EGFP expression was
      observed when the polycistronic constructs were under the control of a CAG
      promoter compared to the CMV promoter, even though the GAG promoter was more
      efficient in this model than the CMV promoter. The study provides guidance on
      design strategies and methods for the efficient generation and expression of 2A
      polycistronic constructs in embryonic stem cells.

PMID- 23139811
TI  - Arbuscular mycorrhizal colonization alters subcellular distribution and chemical
      forms of cadmium in Medicago sativa L. and resists cadmium toxicity.
AB  - Some plants can tolerate and even detoxify soils contaminated with heavy metals.
      This detoxification ability may depend on what chemical forms of metals are taken
      up by plants and how the plants distribute the toxins in their tissues. This, in
      turn, may have an important impact on phytoremediation. We investigated the
      impact of arbuscular mycorrhizal (AM) fungus, Glomus intraradices, on the
      subcellular distribution and chemical forms of cadmium (Cd) in alfalfa (Medicago
      sativa L.) that were grown in Cd-added soils. The fungus significantly colonized
      alfalfa roots by day 25 after planting. Colonization of alfalfa by G.
      intraradices in soils contaminated with Cd ranged from 17% to 69% after 25-60
      days and then decreased to 43%. The biomass of plant shoots with AM fungi showed
      significant 1.7-fold increases compared to no AM fungi addition under the
      treatment of 20 mg kg(-1) Cd. Concentrations of Cd in the shoots of alfalfa under
      0.5, 5, and 20 mgkg(-1) Cd without AM fungal inoculation are 1.87, 2.92, and 2.38
      times higher, respectively, than those of fungi-inoculated plants. Fungal
      inoculation increased Cd (37.2-80.5%) in the cell walls of roots and shoots and
      decreased in membranes after 80 days of incubation compared to untreated plants.
      The proportion of the inactive forms of Cd in roots was higher in fungi-treated
      plants than in controls. Furthermore, although fungi-treated plants had less
      overall Cd in subcellular fragments in shoots, they had more inactive Cd in
      shoots than did control plants. These results provide a basis for further
      research on plant-microbe symbioses in soils contaminated with heavy metals,
      which may potentially help us develop management regimes for phytoremediation.

PMID- 23139812
TI  - Adaptation of the black yeast Wangiella dermatitidis to ionizing radiation:
      molecular and cellular mechanisms.
AB  - Observations of enhanced growth of melanized fungi under low-dose ionizing
      radiation in the laboratory and in the damaged Chernobyl nuclear reactor suggest
      they have adapted the ability to survive or even benefit from exposure to
      ionizing radiation. However, the cellular and molecular mechanism of fungal
      responses to such radiation remains poorly understood. Using the black yeast
      Wangiella dermatitidis as a model, we confirmed that ionizing radiation enhanced
      cell growth by increasing cell division and cell size. Using RNA-seq technology,
      we compared the transcriptomic profiles of the wild type and the melanin
      deficient wdpks1 mutant under irradiation and non-irradiation conditions. It was
      found that more than 3000 genes were differentially expressed when these two
      strains were constantly exposed to a low dose of ionizing radiation and that half
      were regulated at least two fold in either direction. Functional analysis
      indicated that many genes for amino acid and carbohydrate metabolism and cell
      cycle progression were down-regulated and that a number of antioxidant genes and
      genes affecting membrane fluidity were up-regulated in both irradiated strains.
      However, the expression of ribosomal biogenesis genes was significantly up
      regulated in the irradiated wild-type strain but not in the irradiated wdpks1
      mutant, implying that melanin might help to contribute radiation energy for
      protein translation. Furthermore, we demonstrated that long-term exposure to low
      doses of radiation significantly increased survivability of both the wild-type
      and the wdpks1 mutant, which was correlated with reduced levels of reactive
      oxygen species (ROS), increased production of carotenoid and induced expression
      of genes encoding translesion DNA synthesis. Our results represent the first
      functional genomic study of how melanized fungal cells respond to low dose
      ionizing radiation and provide clues for the identification of biological
      processes, molecular pathways and individual genes regulated by radiation.

PMID- 23139813
TI  - Expression at the imprinted dlk1-gtl2 locus is regulated by proneural genes in
      the developing telencephalon.
AB  - Imprinting is an epigenetic mechanism that restrains the expression of about 100
      genes to one allele depending on its parental origin. Several imprinted genes are
      implicated in neurodevelopmental brain disorders, such as autism, Angelman, and
      Prader-Willi syndromes. However, how expression of these imprinted genes is
      regulated during neural development is poorly understood. Here, using single and
      double KO animals for the transcription factors Neurogenin2 (Ngn2) and Achaete
      scute homolog 1 (Ascl1), we found that the expression of a specific subset of
      imprinted genes is controlled by these proneural genes. Using in situ
      hybridization and quantitative PCR, we determined that five imprinted transcripts
      situated at the Dlk1-Gtl2 locus (Dlk1, Gtl2, Mirg, Rian, Rtl1) are upregulated in
      the dorsal telencephalon of Ngn2 KO mice. This suggests that Ngn2 influences the
      expression of the entire Dlk1-Gtl2 locus, independently of the parental origin of
      the transcripts. Interestingly 14 other imprinted genes situated at other
      imprinted loci were not affected by the loss of Ngn2. Finally, using Ngn2/Ascl1
      double KO mice, we show that the upregulation of genes at the Dlk1-Gtl2 locus in
      Ngn2 KO animals requires a functional copy of Ascl1. Our data suggest a complex
      interplay between proneural genes in the developing forebrain that control the
      level of expression at the imprinted Dlk1-Gtl2 locus (but not of other imprinted
      genes). This raises the possibility that the transcripts of this selective locus
      participate in the biological effects of proneural genes in the developing
      telencephalon.

PMID- 23139814
TI  - In a model of Batten disease, palmitoyl protein thioesterase-1 deficiency is
      associated with brown adipose tissue and thermoregulation abnormalities.
AB  - Infantile neuronal ceroid lipofuscinosis (INCL) is a fatal neurodegenerative
      disorder caused by a deficiency of palmitoyl-protein thioesterase-1 (PPT1). We
      have previously shown that children with INCL have increased risk of hypothermia
      during anesthesia and that PPT1-deficiency in mice is associated with disruption
      of adaptive energy metabolism, downregulation of peroxisome proliferator
      activated receptor gamma coactivator 1alpha (PGC-1alpha), and mitochondrial
      dysfunction. Here we hypothesized that Ppt1-knockout mice, a well-studied model
      of INCL that shows many of the neurologic manifestations of the disease, would
      recapitulate the thermoregulation impairment observed in children with INCL. We
      also hypothesized that when exposed to cold, Ppt1-knockout mice would be unable
      to maintain body temperature as in mice thermogenesis requires upregulation of
      Pgc-1alpha and uncoupling protein 1 (Ucp-1) in brown adipose tissue. We found
      that the Ppt1-KO mice had lower basal body temperature as they aged and developed
      hypothermia during cold exposure. Surprisingly, this inability to maintain body
      temperature during cold exposure in Ppt1-KO mice was associated with an adequate
      upregulation of Pgc-1alpha and Ucp-1 but with lower levels of sympathetic
      neurotransmitters in brown adipose tissue. In addition, during baseline
      conditions, brown adipose tissue of Ppt1-KO mice had less vacuolization (lipid
      droplets) compared to wild-type animals. After cold stress, wild-type animals had
      significant decreases whereas Ppt1-KO had insignificant changes in lipid droplets
      compared with baseline measurements, thus suggesting that Ppt1-KO had less
      lipolysis in response to cold stress. These results uncover a previously unknown
      phenotype associated with PPT1 deficiency, that of altered thermoregulation,
      which is associated with impaired lipolysis and neurotransmitter release to brown
      adipose tissue during cold exposure. These findings suggest that INCL should be
      added to the list of neurodegenerative diseases that are linked to alterations in
      peripheral metabolic processes. In addition, extrapolating these findings
      clinically, impaired thermoregulation and hypothermia are potential risks in
      patients with INCL.

PMID- 23139815
TI  - Sequence of closely related plasmids encoding bla(NDM-1) in two unrelated
      Klebsiella pneumoniae isolates in Singapore.
AB  - BACKGROUND: Spread of the bla(NDM-1) gene that encodes the New Delhi metallo-beta
      lactamase (NDM-1) in Enterobacteriaceae is a major global health problem.
      Plasmids carrying bla(NDM-1) from two different multi-drug resistant Klebsiella
      pneumonia isolates collected in Singapore were completely sequenced and compared
      to known plasmids carrying bla(NDM-1). METHODOLOGY/PRINCIPAL FINDINGS: The two
      plasmids, pTR3 and pTR4, were transferred to Escherichia coli recipient strain
      J53 and completely sequenced by a shotgun approach using 3-kb paired-end
      libraries on 454. Although the K. pneumoniae strains were unrelated by molecular
      typing using PFGE and MLST, complete sequencing revealed that pTR3 and pTR4 are
      identical. The plasmid sequence is similar to the E. coli NDM-1-encoding plasmid
      p271A, which was isolated in Australia from a patient returning from Bangladesh.
      The immediate regions of the bla(NDM-1) gene in pTR3/4 are identical to that of
      p271A, but the backbone of our plasmid is much more similar to another IncN2
      plasmid reported recently, pJIE137, which contained an additional 5.2-kb CUP
      (conserved upstream repeat) regulon region in comparison to p271A. A 257-bp
      element bounded by imperfect 39-bp inverted repeats (IR) and an incomplete
      version of this element flanking the 3.6-kb NDM-1-encoding region were identified
      in these plasmids and are likely to be the vestiges of an unknown IS.
      CONCLUSIONS: Although the hosts are not epidemiologically linked, we found that
      the plasmids bearing the bla(NDM-1) gene are identical. Comparative analyses of
      the conserved NDM-1-encoding region among different plasmids from K. pneumoniae
      and E. coli suggested that the transposable elements and the two unknown IR
      associated elements flanking the NDM-1-encoding region might have aided the
      spreading of this worrisome resistance determinant.

PMID- 23139816
TI  - Immunologic response to tumor ablation with irreversible electroporation.
AB  - BACKGROUND: Irreversible electroporation (IRE) is a promising technique for the
      focal treatment of pathologic tissues, which involves placing minimally invasive
      electrodes within the targeted region. However, the knowledge about the
      therapeutic efficacy and immune reactions in response to IRE remains in its
      infancy. METHODS: In this work, to detect whether tumor ablation with IRE could
      trigger the immunologic response, we developed an osteosarcoma rat model and
      applied IRE directly to ablate the tumor. In the experiment, 118 SD rats were
      randomized into 4 groups: the control, sham operation, surgical resection, and
      IRE groups. Another 28 rats without tumor cell implantation served as the normal
      non-tumor-bearing group. We analyzed the changes in T lymphocyte subsets, sIL-2R
      and IL-10 levels in the peripheral blood one day before operation, as well as at
      1, 3, 7,14 and 21 days after the operation. Moreover, splenocytes were assayed
      for IFN-gamma and IL-4 production using intracellular cytokine staining one day
      before the operation, as well as at 7 and 21 days after operation. RESULTS: We
      found that direct IRE completely ablated the tumor cells. A significant increase
      in peripheral lymphocytes, especially CD3(+) and CD4(+) cells, as well as an
      increased ratio of CD4(+)/CD8(+) were detectable 7 days after operation in both
      the IRE and surgical resection groups. Compared with the surgical resection
      group, the IRE group exhibited a stronger cellular immune response. The sIL-2R
      level of the peripheral blood in the IRE group decreased with time and was
      significantly different from that in the surgical resection group. Moreover,
      ablation with IRE significantly increased the percentage of IFN-gamma-positive
      splenocytes. CONCLUSION: These findings indicated that IRE could not only locally
      destroy the tumor but also change the status of cellular immunity in osteosarcoma
      bearing rats. This provides experimental evidence for the clinical application of
      IRE in osteosarcoma treatment.

PMID- 23139817
TI  - Polycomb group proteins bind an engrailed PRE in both the "ON" and "OFF"
      transcriptional states of engrailed.
AB  - Polycomb group (PcG) and trithorax Group (trxG) proteins maintain the "OFF" and
      "ON" transcriptional states of HOX genes and other targets by modulation of
      chromatin structure. In Drosophila, PcG proteins are bound to DNA fragments
      called Polycomb group response elements (PREs). The prevalent model holds that
      PcG proteins bind PREs only in cells where the target gene is "OFF". Another
      model posits that transcription through PREs disrupts associated PcG complexes,
      contributing to the establishment of the "ON" transcriptional state. We tested
      these two models at the PcG target gene engrailed. engrailed exists in a gene
      complex with invected, which together have 4 well-characterized PREs. Our data
      show that these PREs are not transcribed in embryos or larvae. We also examined
      whether PcG proteins are bound to an engrailed PRE in cells where engrailed is
      transcribed. By FLAG-tagging PcG proteins and expressing them specifically where
      engrailed is "ON" or "OFF", we determined that components of three major PcG
      protein complexes are present at an engrailed PRE in both the "ON" and "OFF"
      transcriptional states in larval tissues. These results show that PcG binding per
      se does not determine the transcriptional state of engrailed.

PMID- 23139818
TI  - Cell adhesion signaling regulates RANK expression in osteoclast precursors.
AB  - Cells with monocyte/macrophage lineage expressing receptor activator of NF-kappaB
      (RANK) differentiate into osteoclasts following stimulation with the RANK ligand
      (RANKL). Cell adhesion signaling is also required for osteoclast differentiation
      from precursors. However, details of the mechanism by which cell adhesion signals
      induce osteoclast differentiation have not been fully elucidated. To investigate
      the participation of cell adhesion signaling in osteoclast differentiation, mouse
      bone marrow-derived macrophages (BMMs) were used as osteoclast precursors, and
      cultured on either plastic cell culture dishes (adherent condition) or the top
      surface of semisolid methylcellulose gel loaded in culture tubes (non-adherent
      condition). BMMs cultured under the adherent condition differentiated into
      osteoclasts in response to RANKL stimulation. However, under the non-adherent
      condition, the efficiency of osteoclast differentiation was markedly reduced even
      in the presence of RANKL. These BMMs retained macrophage characteristics
      including phagocytic function and gene expression profile. Lipopolysaccharide
      (LPS) and tumor necrosis factor -alphaTNF-alpha activated the NF-kappaB-mediated
      signaling pathways under both the adherent and non-adherent conditions, while
      RANKL activated the pathways only under the adherent condition. BMMs highly
      expressed RANK mRNA and protein under the adherent condition as compared to the
      non-adherent condition. Also, BMMs transferred from the adherent to non-adherent
      condition showed downregulated RANK expression within 24 hours. In contrast,
      transferring those from the non-adherent to adherent condition significantly
      increased the level of RANK expression. Moreover, interruption of cell adhesion
      signaling by echistatin, an RGD-containing disintegrin, decreased RANK expression
      in BMMs, while forced expression of either RANK or TNFR-associated factor 6
      (TRAF6) in BMMs induced their differentiation into osteoclasts even under the non
      adherent condition. These results suggest that cell adhesion signaling regulates
      RANK expression in osteoclast precursors.

PMID- 23139819
TI  - Doubly Optimized Calibrated Support Vector Machine (DOC-SVM): an algorithm for
      joint optimization of discrimination and calibration.
AB  - Historically, probabilistic models for decision support have focused on
      discrimination, e.g., minimizing the ranking error of predicted outcomes.
      Unfortunately, these models ignore another important aspect, calibration, which
      indicates the magnitude of correctness of model predictions. Using discrimination
      and calibration simultaneously can be helpful for many clinical decisions. We
      investigated tradeoffs between these goals, and developed a unified maximum
      margin method to handle them jointly. Our approach called, Doubly Optimized
      Calibrated Support Vector Machine (DOC-SVM), concurrently optimizes two loss
      functions: the ridge regression loss and the hinge loss. Experiments using three
      breast cancer gene-expression datasets (i.e., GSE2034, GSE2990, and Chanrion's
      datasets) showed that our model generated more calibrated outputs when compared
      to other state-of-the-art models like Support Vector Machine (p=0.03, p=0.13, and
      p<0.001) and Logistic Regression (p=0.006, p=0.008, and p<0.001). DOC-SVM also
      demonstrated better discrimination (i.e., higher AUCs) when compared to Support
      Vector Machine (p=0.38, p=0.29, and p=0.047) and Logistic Regression (p=0.38,
      p=0.04, and p<0.0001). DOC-SVM produced a model that was better calibrated
      without sacrificing discrimination, and hence may be helpful in clinical decision
      making.

PMID- 23139821
TI  - Cardioprotective effect of paeonol and danshensu combination on isoproterenol
      induced myocardial injury in rats.
AB  - BACKGROUND: Traditional Chinese medicinal herbs Cortex Moutan and Radix Salviae
      Milthiorrhizaeare are prescribed together for their putative cardioprotective
      effects in clinical practice. However, the rationale of the combined use remains
      unclear. The present study was designed to investigate the cardioprotective
      effects of paeonol and danshensu (representative active ingredient of Cortex
      Moutan and Radix Salviae Milthiorrhizae, respectively) on isoproterenol-induced
      myocardial infarction in rats and its underlying mechanisms. METHODOLOGY: Paeonol
      (80 mg kg(-1)) and danshensu (160 mg kg(-1)) were administered orally to Sprague
      Dawley rats in individual or in combination for 21 days. At the end of this
      period, rats were administered isoproterenol (85 mg kg(-1)) subcutaneously to
      induce myocardial injury. After induction, rats were anaesthetized with
      pentobarbital sodium (35 mg kg(-1)) to record electrocardiogram, then sacrificed
      and biochemical assays of the heart tissues were performed. PRINCIPAL FINDINGS:
      Induction of rats with isoproterenol resulted in a marked (P<0.001) elevation in
      ST-segment, infarct size, level of serum marker enzymes (CK-MB, LDH, AST and
      ALT), cTnI, TBARS, protein expression of Bax and Caspase-3 and a significant
      decrease in the activities of endogenous antioxidants (SOD, CAT, GPx, GR, and
      GST) and protein expression of Bcl-2. Pretreatment with paeonol and danshensu
      combination showed a significant (P<0.001) decrease in ST-segment elevation,
      infarct size, cTnI, TBARS, protein expression of Bax and Caspase-3 and a
      significant increase in the activities of endogenous antioxidants and protein
      expression of Bcl-2 and Nrf2 when compared with individual treated groups.
      CONCLUSIONS/SIGNIFICANCE: This study demonstrates the cardioprotective effect of
      paeonol and danshensu combination on isoproterenol-induced myocardial infarction
      in rats. The mechanism might be associated with the enhancement of antioxidant
      defense system through activating of Nrf2 signaling and anti-apoptosis through
      regulating Bax, Bcl-2 and Caspase-3. It could provide experimental evidence to
      support the rationality of combinatorial use of traditional Chinese medicine in
      clinical practice.

PMID- 23139820
TI  - Dendritic cell-directed vaccination with a lentivector encoding PSCA for prostate
      cancer in mice.
AB  - Many studies have demonstrated that prostate stem cell antigen (PSCA) is an
      attractive target for immunotherapy based on its overexpression in prostate tumor
      tissue, especially in some metastatic tissues. In this study, we evaluated
      dendritic cell (DC)-directed lentiviral vector (DCLV) encoding murine PSCA (DCLV
      PSCA) as a novel tumor vaccine for prostate cancer in mouse models. We showed
      that DCLV-PSCA could preferentially deliver the PSCA antigen gene to DC-SIGN
      expressing 293T cells and bone marrow-derived DCs (BMDCs). Direct immunization
      with the DCLV-PSCA in male C57BL/6 mice elicited robust PSCA-responsive CD8(+)
      and CD4(+) T cells in vivo. In a transgenic adenocarcinoma mouse prostate cell
      line (TRAMP-C1) synergetic tumor model, we further demonstrated that DCLV-PSCA
      vaccinated mice could be protected from lethal tumor challenge in a prophylactic
      model, whereas slower tumor growth was observed in a therapeutic model. This DCLV
      PSCA vaccine also showed efficacy in inhibiting tumor metastases using a PSCA
      expressing B16-F10 model. Taken together, these data suggest that DCLV is a
      potent vaccine carrier for PSCA in delivering anti-prostate cancer immunity.

PMID- 23139822
TI  - Increased expression of phosphatidylcholine (16:0/18:1) and (16:0/18:2) in
      thyroid papillary cancer.
AB  - A good prognosis can be expected for most, but not all, cases of thyroid
      papillary cancer. Numerous molecular studies have demonstrated beneficial
      treatment and prognostic factors in various molecular markers. Whereas most
      previous reports have focused on genomics and proteomics, few have focused on
      lipidomics. With the advent of mass spectrometry (MS), it has become possible to
      identify many types of molecules, and this analytical tool has become critical in
      the field of omics. Recently, imaging mass spectrometry (IMS) was developed.
      After a simple pretreatment process, IMS can be used to examine tissue sections
      on glass slides with location information.Here, we conducted an IMS analysis of
      seven cases of thyroid papillary cancer by comparison of cancerous with normal
      tissues, focusing on the distribution of phospholipids. We identified that
      phosphatidylcholine (16:0/18:1) and (16:0/18:2) and sphingomyelin (d18:0/16:1)
      are significantly higher in thyroid papillary cancer than in normal thyroid
      tissue as determined by tandem mass (MS/MS) analysis. These distributional
      differences may be associated with the biological behavior of thyroid papillary
      cancer.

PMID- 23139823
TI  - Impact of individual-level social capital on quality of life among AIDS patients
      in China.
AB  - BACKGROUND: With growing recognition of the social determinants of health, social
      capital is an increasingly important construct in international health. However,
      the application of social capital discourse in response to HIV infection remains
      preliminary. The aim of this study was to assess the impact of social capital on
      quality of life (QoL) among adult patients with acquired immune deficiency
      syndrome (AIDS). METHODS: A convenient sample of 283 patients receiving
      antiretroviral treatment (ART) was investigated in Anhui province, China. QoL
      data were collected using the Medical Outcomes Study HIV Survey (MOS-HIV)
      questionnaire. Social capital was measured using a self-developed questionnaire.
      Logistic regression models were used to explore associations between social
      capital and QoL. RESULTS: The study sample had a mean physical health summary
      (PHS) score of 50.13 +/- 9.90 and a mean mental health summary (MHS) score of
      41.64 +/- 11.68. Cronbach's alpha coefficients of the five multi-item scales of
      social capital ranged from 0.44 to 0.79. When other variables were controlled
      for, lower individual levels of reciprocity and trust were associated with a
      greater likelihood of having a poor PHS score (odds ratio [OR] =2.02) or PHS
      score (OR=6.90). Additionally, the factors of social support and social networks
      and ties were associated positively with MHS score (OR=2.30, OR=4.17,
      respectively). CONCLUSIONS: This is the first report to explore the effects of
      social capital on QoL of AIDS patients in China. The results indicate that social
      capital is a promising avenue for developing strategies to improve the QoL of
      AIDS patients in China, suggesting that the contribution of social capital should
      be fully exploited, especially with enhancement of QoL through social
      participation. Social capital development policy may be worthy of consideration.

PMID- 23139824
TI  - Completion of treatment for latent tuberculosis infection with monthly drug
      dispensation directly through the tuberculosis clinic.
AB  - SETTING: An Australian metropolitan TB clinic where treatment for latent
      tuberculosis infection (LTBI) comprises six months of isoniazid, self
      administered but dispensed monthly by the clinic. OBJECTIVE: To determine the
      proportion of patients who complete treatment for LTBI and to identify factors
      associated with non-completion. METHODS: Clinical files of all patients receiving
      treatment for LTBI between 01/2000 and 12/2010 were reviewed. The study
      population comprised all patients who were commenced on isoniazid as treatment
      for LTBI. Odds ratios (OR) for completing treatment were estimated by logistic
      regression. RESULTS: Of 216 patients who commenced isoniazid treatment for LTBI,
      163 (75%) completed six months treatment [corrected]. Fifty-three percent of the
      53 patients who did not complete treatment dropped out after three months
      treatment. The mean (SD) age of the patients was 27 (16) years and 123 (57%) were
      female. The majority of patients (59%) were born overseas and 69% received
      treatment for LTBI because they were contacts of patients with TB. Patients' sex,
      age, country of birth, time since immigration for overseas born people, health
      care worker status, TST conversion status, chest x-ray findings, language,
      employment status and the indication for which treatment of LTBI was prescribed
      were not significantly related to treatment completion. CONCLUSION: In a setting
      where isoniazid is dispensed monthly by the TB clinic, a relatively high
      proportion of patients who commence treatment for LTBI complete the six month
      scheduled course of treatment. The study did not identify any patient
      characteristics that predicted treatment completion. Interventions to improve
      completion rates should extend over the whole duration of treatment.

PMID- 23139825
TI  - Distinct cellular and subcellular distributions of G protein-coupled receptor
      kinase and arrestin isoforms in the striatum.
AB  - G protein-coupled receptor kinases (GRKs) and arrestins mediate desensitization
      of G protein-coupled receptors (GPCR). Arrestins also mediate G protein
      independent signaling via GPCRs. Since GRK and arrestins demonstrate no strict
      receptor specificity, their functions in the brain may depend on their cellular
      complement, expression level, and subcellular targeting. However, cellular
      expression and subcellular distribution of GRKs and arrestins in the brain is
      largely unknown. We show that GRK isoforms GRK2 and GRK5 are similarly expressed
      in direct and indirect pathway neurons in the rat striatum. Arrestin-2 and
      arrestin-3 are also expressed in neurons of both pathways. Cholinergic
      interneurons are enriched in GRK2, arrestin-3, and GRK5. Parvalbumin-positive
      interneurons express more of GRK2 and less of arrestin-2 than medium spiny
      neurons. The GRK5 subcellular distribution in the human striatal neurons is
      altered by its phosphorylation: unphosphorylated enzyme preferentially localizes
      to synaptic membranes, whereas phosphorylated GRK5 is found in plasma membrane
      and cytosolic fractions. Both GRK isoforms are abundant in the nucleus of human
      striatal neurons, whereas the proportion of both arrestins in the nucleus was
      equally low. However, overall higher expression of arrestin-2 yields high enough
      concentration in the nucleus to mediate nuclear functions. These data suggest
      cell type- and subcellular compartment-dependent differences in GRK/arrestin
      mediated desensitization and signaling.

PMID- 23139826
TI  - Random phenotypic variation of yeast (Saccharomyces cerevisiae) single-gene
      knockouts fits a double pareto-lognormal distribution.
AB  - BACKGROUND: Distributed robustness is thought to influence the buffering of
      random phenotypic variation through the scale-free topology of gene regulatory,
      metabolic, and protein-protein interaction networks. If this hypothesis is true,
      then the phenotypic response to the perturbation of particular nodes in such a
      network should be proportional to the number of links those nodes make with
      neighboring nodes. This suggests a probability distribution approximating an
      inverse power-law of random phenotypic variation. Zero phenotypic variation,
      however, is impossible, because random molecular and cellular processes are
      essential to normal development. Consequently, a more realistic distribution
      should have a y-intercept close to zero in the lower tail, a mode greater than
      zero, and a long (fat) upper tail. The double Pareto-lognormal (DPLN)
      distribution is an ideal candidate distribution. It consists of a mixture of a
      lognormal body and upper and lower power-law tails. OBJECTIVE AND METHODS: If our
      assumptions are true, the DPLN distribution should provide a better fit to random
      phenotypic variation in a large series of single-gene knockout lines than other
      skewed or symmetrical distributions. We fit a large published data set of single
      gene knockout lines in Saccharomyces cerevisiae to seven different probability
      distributions: DPLN, right Pareto-lognormal (RPLN), left Pareto-lognormal (LPLN),
      normal, lognormal, exponential, and Pareto. The best model was judged by the
      Akaike Information Criterion (AIC). RESULTS: Phenotypic variation among gene
      knockouts in S. cerevisiae fits a double Pareto-lognormal (DPLN) distribution
      better than any of the alternative distributions, including the right Pareto
      lognormal and lognormal distributions. CONCLUSIONS AND SIGNIFICANCE: A DPLN
      distribution is consistent with the hypothesis that developmental stability is
      mediated, in part, by distributed robustness, the resilience of gene regulatory,
      metabolic, and protein-protein interaction networks. Alternatively,
      multiplicative cell growth, and the mixing of lognormal distributions having
      different variances, may generate a DPLN distribution.

PMID- 23139827
TI  - Angiotensin-(1-7) in paraventricular nucleus modulates sympathetic activity and
      cardiac sympathetic afferent reflex in renovascular hypertensive rats.
AB  - BACKGROUND: Excessive sympathetic activity contributes to the pathogenesis and
      progression of hypertension. Enhanced cardiac sympathetic afferent reflex (CSAR)
      is involved in sympathetic activation. This study was designed to determine the
      roles of angiotensin (Ang)-(1-7) in paraventricular nucleus (PVN) in modulating
      sympathetic activity and CSAR and its signal pathway in renovascular
      hypertension. METHODOLOGY/PRINCIPAL FINDINGS: Renovascular hypertension was
      induced with two-kidney, one-clip method. Renal sympathetic nerve activity (RSNA)
      and mean arterial pressure (MAP) were recorded in sinoaortic-denervated and
      cervical-vagotomized rats with anesthesia. CSAR was evaluated with the RSNA and
      MAP responses to epicardial application of capsaicin. PVN microinjection of Ang
      (1-7) and cAMP analogue db-cAMP caused greater increases in RSNA and MAP, and
      enhancement in CSAR in hypertensive rats than in sham-operated rats, while Mas
      receptor antagonist A-779 produced opposite effects. There was no significant
      difference in the angiotensin-converting enzyme 2 (ACE2) activity and Ang-(1-7)
      level in the PVN between sham-operated rats and hypertensive rats, but the Mas
      receptor protein expression in the PVN was increased in hypertensive rats. The
      effects of Ang-(1-7) were abolished by A-779, adenylyl cyclase inhibitor SQ22536
      or protein kinase A (PKA) inhibitor Rp-cAMP. SQ22536 or Rp-cAMP reduced RSNA and
      MAP in hypertensive rats, and attenuated the CSAR in both sham-operated and
      hypertensive rats. CONCLUSIONS: Ang-(1-7) in the PVN increases RSNA and MAP and
      enhances the CSAR, which is mediated by Mas receptors. Endogenous Ang-(1-7) and
      Mas receptors contribute to the enhanced sympathetic outflow and CSAR in
      renovascular hypertension. A cAMP-PKA pathway is involved in the effects of Ang
      (1-7) in the PVN.

PMID- 23139828
TI  - Prion seeding activities of mouse scrapie strains with divergent PrPSc protease
      sensitivities and amyloid plaque content using RT-QuIC and eQuIC.
AB  - Different transmissible spongiform encephalopathy (TSE)-associated forms of prion
      protein (e.g. PrP(Sc)) can vary markedly in ultrastructure and biochemical
      characteristics, but each is propagated in the host. PrP(Sc) propagation involves
      conversion from its normal isoform, PrP(C), by a seeded or templated
      polymerization mechanism. Such a mechanism is also the basis of the RT-QuIC and
      eQuIC prion assays which use recombinant PrP (rPrP(Sen)) as a substrate. These
      ultrasensitive detection assays have been developed for TSE prions of several
      host species and sample tissues, but not for murine models which are central to
      TSE pathogenesis research. Here we have adapted RT-QuIC and eQuIC to various
      murine prions and evaluated how seeding activity depends on
      glycophosphatidylinositol (GPI) anchoring and the abundance of amyloid plaques
      and protease-resistant PrP(Sc) (PrP(Res)). Scrapie brain dilutions up to 10(-8)
      and 10(-13) were detected by RT-QuIC and eQuIC, respectively. Comparisons of
      scrapie-affected wild-type mice and transgenic mice expressing GPI anchorless PrP
      showed that, although similar concentrations of seeding activity accumulated in
      brain, the heavily amyloid-laden anchorless mouse tissue seeded more rapid
      reactions. Next we compared seeding activities in the brains of mice with similar
      infectivity titers, but widely divergent PrP(Res) levels. For this purpose we
      compared the 263K and 139A scrapie strains in transgenic mice expressing P101L
      PrP(C). Although the brains of 263K-affected mice had little immunoblot
      detectable PrP(Res), RT-QuIC indicated that seeding activity was comparable to
      that associated with a high-PrP(Res) strain, 139A. Thus, in this comparison, RT
      QuIC seeding activity correlated more closely with infectivity than with PrP(Res)
      levels. We also found that eQuIC, which incorporates a PrP(Sc)
      immunoprecipitation step, detected seeding activity in plasma from wild-type and
      anchorless PrP transgenic mice inoculated with 22L, 79A and/or RML scrapie
      strains. Overall, we conclude that these new mouse-adapted prion seeding assays
      detect diverse types of PrP(Sc).

PMID- 23139829
TI  - Reduction of type IV collagen by upregulated miR-29 in normal elderly mouse and
      klotho-deficient, senescence-model mouse.
AB  - MicroRNA (miRNA), a small non-coding RNA that functions as a mediator in gene
      silencing, plays important roles in gene regulation in various vital functions
      and activities. Here we show that the miR-29 members are upregulated in klotho
      deficient [klotho(-/-)] mice, a senescence-model animal, and also in normal
      elderly ICR mice relative to wild-type littermates and young ICR mice. In
      addition, levels of type IV collagen, a major component of basement membranes and
      a putative target of miR-29, were lower in klotho(-/-) and elderly ICR mice than
      in wild-type littermates and young ICR mice. RNA degradation mediated by miR-29
      may participate in the suppression of type IV collagen, both in vivo and in
      vitro. Taken together, our current findings suggest that the miR-29 upregulated
      in aging may be involved in the downregulation of type IV collagen, leading to a
      possible weakening of the basal membrane in senescent tissues, and miR-29 may be
      a useful molecular marker of senescence.

PMID- 23139830
TI  - Mice genetically depleted of brain serotonin display social impairments,
      communication deficits and repetitive behaviors: possible relevance to autism.
AB  - Autism is a complex neurodevelopmental disorder characterized by impaired
      reciprocal social interaction, communication deficits and repetitive behaviors. A
      very large number of genes have been linked to autism, many of which encode
      proteins involved in the development and function of synaptic circuitry. However,
      the manner in which these mutated genes might participate, either individually or
      together, to cause autism is not understood. One factor known to exert extremely
      broad influence on brain development and network formation, and which has been
      linked to autism, is the neurotransmitter serotonin. Unfortunately, very little
      is known about how alterations in serotonin neuronal function might contribute to
      autism. To test the hypothesis that serotonin dysfunction can contribute to the
      core symptoms of autism, we analyzed mice lacking brain serotonin (via a null
      mutation in the gene for tryptophan hydroxylase 2 (TPH2)) for behaviors that are
      relevant to this disorder. Mice lacking brain serotonin (TPH2-/-) showed
      substantial deficits in numerous validated tests of social interaction and
      communication. These mice also display highly repetitive and compulsive
      behaviors. Newborn TPH2-/- mutant mice show delays in the expression of key
      developmental milestones and their diminished preference for maternal scents over
      the scent of an unrelated female is a forerunner of more severe socialization
      deficits that emerge in weanlings and persist into adulthood. Taken together,
      these results indicate that a hypo-serotonin condition can lead to behavioral
      traits that are highly characteristic of autism. Our findings should stimulate
      new studies that focus on determining how brain hyposerotonemia during critical
      neurodevelopmental periods can alter the maturation of synaptic circuits known to
      be mis-wired in autism and how prevention of such deficits might prevent this
      disorder.

PMID- 23139831
TI  - Decreased coherent motion discrimination in autism spectrum disorder: the role of
      attentional zoom-out deficit.
AB  - Autism spectrum disorder (ASD) has been associated with decreased coherent dot
      motion (CDM) performance, a task that measures magnocellular sensitivity as well
      as fronto-parietal attentional integration processing. In order to clarify the
      role of spatial attention in CDM tasks, we measured the perception of coherently
      moving dots displayed in the central or peripheral visual field in ASD and
      typically developing children. A dorsal-stream deficit in children with ASD
      should predict a generally poorer performance in both conditions. In our study,
      however, we show that in children with ASD, CDM perception was selectively
      impaired in the central condition. In addition, in the ASD group, CDM efficiency
      was correlated to the ability to zoom out the attentional focus. Importantly,
      autism symptoms severity was related to both the CDM and attentional zooming-out
      impairment. These findings suggest that a dysfunction in the attentional network
      might help to explain decreased CDM discrimination as well as the "core" social
      cognition deficits of ASD.

PMID- 23139832
TI  - Consequences of exchanging carbohydrates for proteins in the cholesterol
      metabolism of mice fed a high-fat diet.
AB  - Consumption of low-carbohydrate, high-protein, high-fat diets lead to rapid
      weight loss but the cardioprotective effects of these diets have been questioned.
      We examined the impact of high-protein and high-fat diets on cholesterol
      metabolism by comparing the plasma cholesterol and the expression of cholesterol
      biosynthesis genes in the liver of mice fed a high-fat (HF) diet that has a high
      (H) or a low (L) protein-to-carbohydrate (P/C) ratio. H-P/C-HF feeding, compared
      with L-P/C-HF feeding, decreased plasma total cholesterol and increased HDL
      cholesterol concentrations at 4-wk. Interestingly, the expression of genes
      involved in hepatic steroid biosynthesis responded to an increased dietary P/C
      ratio by first down-regulation (2-d) followed by later up-regulation at 4-wk, and
      the temporal gene expression patterns were connected to the putative activity of
      SREBF1 and 2. In contrast, Cyp7a1, the gene responsible for the conversion of
      cholesterol to bile acids, was consistently up-regulated in the H-P/C-HF liver
      regardless of feeding duration. Over expression of Cyp7a1 after 2-d and 4-wk H
      P/C-HF feeding was connected to two unique sets of transcription regulators. At
      both time points, up-regulation of the Cyp7a1 gene could be explained by enhanced
      activations and reduced suppressions of multiple transcription regulators. In
      conclusion, we demonstrated that the hypocholesterolemic effect of H-P/C-HF
      feeding coincided with orchestrated changes of gene expressions in lipid
      metabolic pathways in the liver of mice. Based on these results, we hypothesize
      that the cholesterol lowering effect of high-protein feeding is associated with
      enhanced bile acid production but clinical validation is warranted. (246 words).

PMID- 23139833
TI  - L-carnitine is an endogenous HDAC inhibitor selectively inhibiting cancer cell
      growth in vivo and in vitro.
AB  - L-carnitine (LC) is generally believed to transport long-chain acyl groups from
      fatty acids into the mitochondrial matrix for ATP generation via the citric acid
      cycle. Based on Warburg's theory that most cancer cells mainly depend on
      glycolysis for ATP generation, we hypothesize that, LC treatment would lead to
      disturbance of cellular metabolism and cytotoxicity in cancer cells. In this
      study, Human hepatoma HepG2, SMMC-7721 cell lines, primary cultured thymocytes
      and mice bearing HepG2 tumor were used. ATP content was detected by HPLC assay.
      Cell cycle, cell death and cell viability were assayed by flow cytometry and MTS
      respectively. Gene, mRNA expression and protein level were detected by gene
      microarray, Real-time PCR and Western blot respectively. HDAC activities and
      histone acetylation were detected both in test tube and in cultured cells. A
      molecular docking study was carried out with CDOCKER protocol of Discovery Studio
      2.0 to predict the molecular interaction between L-carnitine and HDAC. Here we
      found that (1) LC treatment selectively inhibited cancer cell growth in vivo and
      in vitro; (2) LC treatment selectively induces the expression of p21(cip1) gene,
      mRNA and protein in cancer cells but not p27(kip1); (4) LC increases histone
      acetylation and induces accumulation of acetylated histones both in normal
      thymocytes and cancer cells; (5) LC directly inhibits HDAC I/II activities via
      binding to the active sites of HDAC and induces histone acetylation and lysine
      acetylation accumulation in vitro; (6) LC treatment induces accumulation of
      acetylated histones in chromatin associated with the p21(cip1) gene but not
      p27(kip1) detected by ChIP assay. These data support that LC, besides
      transporting acyl group, works as an endogenous HDAC inhibitor in the cell, which
      would be of physiological and pathological importance.

PMID- 23139834
TI  - Phosphorylation controls the localization and activation of the lumenal carbonic
      anhydrase in Chlamydomonas reinhardtii.
AB  - BACKGROUND: Cah3 is the only carbonic anhydrase (CA) isoform located in the
      thylakoid lumen of Chlamydomonas reinhardtii. Previous studies demonstrated its
      association with the donor side of the photosystem II (PSII) where it is required
      for the optimal function of the water oxidizing complex. However this enzyme has
      also been frequently proposed to perform a critical function in inorganic carbon
      acquisition and CO(2) fixation and all mutants lacking Cah3 exhibit very poor
      growth after transfer to low CO(2) conditions. RESULTS/CONCLUSIONS: In the
      present work we demonstrate that after transfer to low CO(2), Cah3 is
      phosphorylated and that phosphorylation is correlated to changes in its
      localization and its increase in activity. When C. reinhardtii wild-type cells
      were acclimated to limiting CO(2) conditions, the Cah3 activity increased about 5
      6 fold. Under these conditions, there were no detectable changes in the level of
      the Cah3 polypeptide. The increase in activity was specifically inhibited in the
      presence of Staurosporine, a protein kinase inhibitor, suggesting that the Cah3
      protein was post-translationally regulated via phosphorylation.
      Immunoprecipitation and in vitro dephosphorylation experiments confirm this
      hypothesis. In vivo phosphorylation analysis of thylakoid polypeptides indicates
      that there was a 3-fold increase in the phosphorylation signal of the Cah3
      polypeptide within the first two hours after transfer to low CO(2) conditions.
      The increase in the phosphorylation signal was correlated with changes in the
      intracellular localization of the Cah3 protein. Under high CO(2) conditions, the
      Cah3 protein was only associated with the donor side of PSII in the stroma
      thylakoids. In contrast, in cells grown at limiting CO(2) the protein was partly
      concentrated in the thylakoids crossing the pyrenoid, which did not contain PSII
      and were surrounded by Rubisco molecules. SIGNIFICANCE: This is the first report
      of a CA being post-translationally regulated and describing phosphorylation
      events in the thylakoid lumen.

PMID- 23139835
TI  - Identification of pOENI-1 and related plasmids in Oenococcus oeni strains
      performing the malolactic fermentation in wine.
AB  - Plasmids in lactic acid bacteria occasionally confer adaptive advantages
      improving the growth and behaviour of their host cells. They are often associated
      to starter cultures used in the food industry and could be a signature of their
      superiority. Oenococcus oeni is the main lactic acid bacteria species encountered
      in wine. It performs the malolactic fermentation that occurs in most wines after
      alcoholic fermentation and contributes to their quality and stability. Industrial
      O. oeni starters may be used to better control malolactic fermentation. Starters
      are selected empirically by virtue of their fermentation kinetics and capacity to
      survive in wine. This study was initiated with the aim to determine whether O.
      oeni contains plasmids of technological interest. Screening of 11 starters and 33
      laboratory strains revealed two closely related plasmids, named pOENI-1 (18.3-kb)
      and pOENI-1v2 (21.9-kb). Sequence analyses indicate that they use the theta mode
      of replication, carry genes of maintenance and replication and two genes possibly
      involved in wine adaptation encoding a predicted sulphite exporter (tauE) and a
      NADH:flavin oxidoreductase of the old yellow enzyme family (oye). Interestingly,
      pOENI-1 and pOENI-1v2 were detected only in four strains, but this included three
      industrial starters. PCR screenings also revealed that tauE is present in six of
      the 11 starters, being probably inserted in the chromosome of some strains.
      Microvinification assays performed using strains with and without plasmids did
      not disclose significant differences of survival in wine or fermentation
      kinetics. However, analyses of 95 wines at different phases of winemaking showed
      that strains carrying the plasmids or the genes tauE and oye were predominant
      during spontaneous malolactic fermentation. Taken together, the results revealed
      a family of related plasmids associated with industrial starters and indigenous
      strains performing spontaneous malolactic fermentation that possibly contribute
      to the technological performance of strains in wine.

PMID- 23139836
TI  - Dynamic epidemiological models for dengue transmission: a systematic review of
      structural approaches.
AB  - Dengue is a vector-borne disease recognized as the major arbovirose with four
      immunologically distant dengue serotypes coexisting in many endemic areas.
      Several mathematical models have been developed to understand the transmission
      dynamics of dengue, including the role of cross-reactive antibodies for the four
      different dengue serotypes. We aimed to review deterministic models of dengue
      transmission, in order to summarize the evolution of insights for, and provided
      by, such models, and to identify important characteristics for future model
      development. We identified relevant publications using PubMed and ISI Web of
      Knowledge, focusing on mathematical deterministic models of dengue transmission.
      Model assumptions were systematically extracted from each reviewed model
      structure, and were linked with their underlying epidemiological concepts. After
      defining common terms in vector-borne disease modelling, we generally categorised
      fourty-two published models of interest into single serotype and multiserotype
      models. The multi-serotype models assumed either vector-host or direct host-to
      host transmission (ignoring the vector component). For each approach, we
      discussed the underlying structural and parameter assumptions, threshold
      behaviour and the projected impact of interventions. In view of the expected
      availability of dengue vaccines, modelling approaches will increasingly focus on
      the effectiveness and cost-effectiveness of vaccination options. For this
      purpose, the level of representation of the vector and host populations seems
      pivotal. Since vector-host transmission models would be required for projections
      of combined vaccination and vector control interventions, we advocate their use
      as most relevant to advice health policy in the future. The limited understanding
      of the factors which influence dengue transmission as well as limited data
      availability remain important concerns when applying dengue models to real-world
      decision problems.

PMID- 23139837
TI  - Morphology, classification, and distribution of the projection neurons in the
      dorsal lateral geniculate nucleus of the rat.
AB  - The morphology of confirmed projection neurons in the dorsal lateral geniculate
      nucleus (dLGN) of the rat was examined by filling these cells retrogradely with
      biotinylated dextran amine (BDA) injected into the visual cortex. BDA-labeled
      projection neurons varied widely in the shape and size of their cell somas, with
      mean cross-sectional areas ranging from 60-340 um(2). Labeled projection neurons
      supported 7-55 dendrites that spanned up to 300 um in length and formed dendritic
      arbors with cross-sectional areas of up to 7.0 * 10(4) um(2). Primary dendrites
      emerged from cell somas in three broad patterns. In some dLGN projection neurons,
      primary dendrites arise from the cell soma at two poles spaced approximately 180
      degrees  apart. In other projection neurons, dendrites emerge principally from
      one side of the cell soma, while in a third group of projection neurons primary
      dendrites emerge from the entire perimeter of the cell soma. Based on these three
      distinct patterns in the distribution of primary dendrites from cell somas, we
      have grouped dLGN projection neurons into three classes: bipolar cells, basket
      cells and radial cells, respectively. The appendages seen on dendrites also can
      be grouped into three classes according to differences in their structure. Short
      "tufted" appendages arise mainly from the distal branches of dendrites; "spine
      like" appendages, fine stalks with ovoid heads, typically are seen along the
      middle segments of dendrites; and "grape-like" appendages, short stalks that
      terminate in a cluster of ovoid bulbs, appear most often along the proximal
      segments of secondary dendrites of neurons with medium or large cell somas. While
      morphologically diverse dLGN projection neurons are intermingled uniformly
      throughout the nucleus, the caudal pole of the dLGN contains more small
      projection neurons of all classes than the rostral pole.

PMID- 23139838
TI  - Dynamic mechanisms of cell rigidity sensing: insights from a computational model
      of actomyosin networks.
AB  - Cells modulate themselves in response to the surrounding environment like
      substrate elasticity, exhibiting structural reorganization driven by the
      contractility of cytoskeleton. The cytoskeleton is the scaffolding structure of
      eukaryotic cells, playing a central role in many mechanical and biological
      functions. It is composed of a network of actins, actin cross-linking proteins
      (ACPs), and molecular motors. The motors generate contractile forces by sliding
      couples of actin filaments in a polar fashion, and the contractile response of
      the cytoskeleton network is known to be modulated also by external stimuli, such
      as substrate stiffness. This implies an important role of actomyosin
      contractility in the cell mechano-sensing. However, how cells sense matrix
      stiffness via the contractility remains an open question. Here, we present a 3-D
      Brownian dynamics computational model of a cross-linked actin network including
      the dynamics of molecular motors and ACPs. The mechano-sensing properties of this
      active network are investigated by evaluating contraction and stress in response
      to different substrate stiffness. Results demonstrate two mechanisms that act to
      limit internal stress: (i) In stiff substrates, motors walk until they exert
      their maximum force, leading to a plateau stress that is independent of substrate
      stiffness, whereas (ii) in soft substrates, motors walk until they become blocked
      by other motors or ACPs, leading to submaximal stress levels. Therefore, this
      study provides new insights into the role of molecular motors in the contraction
      and rigidity sensing of cells.

PMID- 23139839
TI  - Virucidal nanofiber textiles based on photosensitized production of singlet
      oxygen.
AB  - Novel biomaterials based on hydrophilic polycaprolactone and polyurethane
      (Tecophilic(r)) nanofibers with an encapsulated 5,10,5,20-tetraphenylporphyrin
      photosensitizer were prepared by electrospinning. The doped nanofiber textiles
      efficiently photo-generate O(2)((1)Delta(g)), which oxidize external chemical and
      biological substrates/targets. Strong photo-virucidal effects toward non
      enveloped polyomaviruses and enveloped baculoviruses were observed on the surface
      of these textiles. The photo-virucidal effect was confirmed by a decrease in
      virus infectivity. In contrast, no virucidal effect was detected in the absence
      of light and/or the encapsulated photosensitizer.

PMID- 23139840
TI  - Functional characterization of calcineurin homologs PsCNA1/PsCNB1 in Puccinia
      striiformis f. sp. tritici using a host-induced RNAi system.
AB  - Calcineurin plays a key role in morphogenesis, pathogenesis and drug resistance
      in most fungi. However, the function of calcineurin genes in Puccinia striiformis
      f. sp. tritici (Pst) is unclear. We identified and characterized the calcineurin
      genes PsCNA1 and PsCNB1 in Pst. Phylogenetic analyses indicate that PsCNA1 and
      PsCNB1 form a calcium/calmodulin regulated protein phosphatase belonging to the
      calcineurin heterodimers composed of subunits A and B. Quantitative RT-PCR
      analyses revealed that both PsCNA1 and PsCNB1 expression reached their maximum in
      the stage of haustorium formation, which is one day after inoculation. Using
      barely stripe mosaic virus (BSMV) as a transient expression vector in wheat, the
      expression of PsCNA1 and PsCNB1 in Pst was suppressed, leading to slower
      extension of fungal hyphae and reduced production of urediospores. The immune
      suppressive drugs cyclosporin A and FK506 markedly reduced the germination rates
      of urediospores, and when germination did occur, more than two germtubes were
      produced. These results suggest that the calcineurin signaling pathway
      participates in stripe rust morphogenetic differentiation, especially the
      formation of haustoria during the early stage of infection and during the
      production of urediospores. Therefore PsCNA1 and PsCNB1 can be considered
      important pathogenicity genes involved in the wheat-Pst interaction.

PMID- 23139841
TI  - Neutral lipid metabolism influences phospholipid synthesis and deacylation in
      Saccharomyces cerevisiae.
AB  - Establishment and maintenance of equilibrium in the fatty acid (FA) composition
      of phospholipids (PL) requires both regulation of the substrate available for PL
      synthesis (the acyl-CoA pool) and extensive PL turnover and acyl editing. In the
      present study, we utilize acyl-CoA synthetase (ACS) deficient cells, unable to
      recycle FA derived from lipid deacylation, to evaluate the role of several
      enzymatic activities in FA trafficking and PL homeostasis in Saccharomyces
      cerevisiae. The data presented show that phospholipases B are not contributing to
      constitutive PL deacylation and are therefore unlikely to be involved in PL
      remodeling. In contrast, the enzymes of neutral lipid (NL) synthesis and
      mobilization are central mediators of FA trafficking. The phospholipid:DAG
      acyltransferase (PDAT) Lro1p has a substantial effect on FA release and on PL
      equilibrium, emerging as an important mediator in PL remodeling. The acyl-CoA
      dependent biosynthetic activities of NL metabolism are also involved in PL
      homeostasis through active modulation of the substrate available for PL
      synthesis. In addition TAG mobilization makes an important contribution,
      especially in cells from stationary phase, to FA availability. Beyond its well
      established role in the formation of a storage pool, NL metabolism could play a
      crucial role as a mechanism to uncouple the pools of PL and acyl-CoAs from each
      other and thereby to allow independent regulation of each one.

PMID- 23139842
TI  - Treatment with a nitric oxide-donating NSAID alleviates functional muscle
      ischemia in the mouse model of Duchenne muscular dystrophy.
AB  - In patients with Duchenne muscular dystrophy (DMD) and the standard mdx mouse
      model of DMD, dystrophin deficiency causes loss of neuronal nitric oxide synthase
      (nNOSMU) from the sarcolemma, producing functional ischemia when the muscles are
      exercised. We asked if functional muscle ischemia would be eliminated and normal
      blood flow regulation restored by treatment with an exogenous nitric oxide (NO)
      donating drug. Beginning at 8 weeks of age, mdx mice were fed a standard diet
      supplemented with 1% soybean oil alone or in combination with a low (15 mg/kg) or
      high (45 mg/kg) dose of HCT 1026, a NO-donating nonsteroidal anti-inflammatory
      agent which has previously been shown to slow disease progression in the mdx
      model. After 1 month of treatment, vasoconstrictor responses to intra-arterial
      norepinephrine (NE) were compared in resting and contracting hindlimbs. In
      untreated mdx mice, the usual effect of muscle contraction to attenuate NE
      mediated vasoconstriction was impaired, resulting in functional ischemia: NE
      evoked similar decreases in femoral blood flow velocity and femoral vascular
      conductance (FVC) in the contracting compared to resting hindlimbs (DeltaFVC
      contraction/DeltaFVC rest=0.88 +/- 0.03). NE-induced functional ischemia was
      unaffected by low dose HCT 1026 (DeltaFVC ratio=0.92 +/- 0.04; P>0.05 vs
      untreated), but was alleviated by the high dose of the drug (DeltaFVC ratio=0.22
      +/- 0.03; P<0.05 vs untreated or low dose). The beneficial effect of high dose
      HCT 1026 was maintained with treatment up to 3 months. The effect of the NO
      donating drug HCT 1026 to normalize blood flow regulation in contracting mdx
      mouse hindlimb muscles suggests a putative novel treatment for DMD. Further
      translational research is warranted.

PMID- 23139843
TI  - Otx but not Mitf transcription factors are required for zebrafish retinal pigment
      epithelium development.
AB  - Otx and Mitf transcription factors have been implicated in the development of the
      retinal pigmented epithelium (RPE), but the relationship between these factors
      and their specific roles in the development of the RPE have not been fully
      defined. The role of the three Otx transcription factors (Otx1a, Otx1b, and Otx2)
      and two Mitf transcription factors (Mitfa and Mitfb) in the development of the
      zebrafish RPE was explored in these experiments. The loss of Otx activity through
      morpholino knockdown produced variable eye defects, ranging from delayed RPE
      pigmentation to severe coloboma, depending on the combination of Otx factors that
      were targeted. Expression analysis through in situ hybridization demonstrates
      that otx transcription factors are necessary for the proper expression of mitfa
      and mitfb while Mitf transcription factors are not required for the expression of
      otx genes. Surprisingly, the loss of Mitf activity in mitfa, mitfb, or double
      mitf mutant zebrafish had no effect on RPE pigmentation or development. Moreover,
      histological analysis revealed that retinal lamination is unaffected in mitf
      mutants, as well as in otx morphants, even in regions lacking RPE. Otx and Mitf
      combined loss of function experiments suggest that mitfa and mitfb may still
      influence zebrafish RPE development. This is further supported by the ability of
      mitfa to induce pigmentation in the zebrafish retina when misexpressed. These
      findings suggest that one or more Otx targets in addition to mitfa and mitfb,
      possibly another mitf family member, are necessary for development of the RPE in
      zebrafish.

PMID- 23139844
TI  - Sigma-1 receptor agonists directly inhibit Nav1.2/1.4 channels.
AB  - (+)-SKF 10047 (N-allyl-normetazocine) is a prototypic and specific sigma-1
      receptor agonist that has been used extensively to study the function of sigma-1
      receptors. (+)-SKF 10047 inhibits K(+), Na(+) and Ca2+ channels via sigma-1
      receptor activation. We found that (+)-SKF 10047 inhibited Na(V)1.2 and Na(V)1.4
      channels independently of sigma-1 receptor activation. (+)-SKF 10047 equally
      inhibited Na(V)1.2/1.4 channel currents in HEK293T cells with abundant sigma-1
      receptor expression and in COS-7 cells, which barely express sigma-1 receptors.
      The sigma-1 receptor antagonists BD 1063,BD 1047 and NE-100 did not block the
      inhibitory effects of (+)-SKF-10047. Blocking of the PKA, PKC and G-protein
      pathways did not affect (+)-SKF 10047 inhibition of Na(V)1.2 channel currents.
      The sigma-1 receptor agonists Dextromethorphan (DM) and 1,3-di-o-tolyl-guanidine
      (DTG) also inhibited Na(V)1.2 currents through a sigma-1 receptor-independent
      pathway. The (+)-SKF 10047 inhibition of Na(V)1.2 currents was use- and frequency
      dependent. Point mutations demonstrated the importance of Phe(1764) and Tyr(1771)
      in the IV-segment 6 domain of the Na(V)1.2 channel and Phe(1579) in the Na(V)1.4
      channel for (+)-SKF 10047 inhibition. In conclusion, our results suggest that
      sigma-1 receptor agonists directly inhibit Na(V)1.2/1.4 channels and that these
      interactions should be given special attention for future sigma-1 receptor
      function studies.

PMID- 23139846
TI  - Number Combinations Remediation for Students with Mathematics Difficulty.

PMID- 23139845
TI  - Simultaneous RNA-seq analysis of a mixed transcriptome of rice and blast fungus
      interaction.
AB  - A filamentous fungus, Magnaporthe oryzae, is a causal agent of rice blast
      disease, which is one of the most serious diseases affecting cultivated rice,
      Oryza sativa. However, the molecular mechanisms underlying both rice defense and
      fungal attack are not yet fully understood. Extensive past studies have
      characterized many infection-responsive genes in the pathogen and host plant,
      separately. To understand the plant-pathogen interaction comprehensively, it is
      valuable to monitor the gene expression profiles of both interacting organisms
      simultaneously in the same infected plant tissue. Although the host-pathogen
      interaction during the initial infection stage is important for the establishment
      of infection, the detection of fungal gene expression in infected leaves at the
      stage has been difficult because very few numbers of fungal cells are present.
      Using the emerging RNA-Seq technique, which has a wide dynamic range for
      expression analyses, we analyzed the mixed transcriptome of rice and blast fungus
      in infected leaves at 24 hours post-inoculation, which is the point when the
      primary infection hyphae penetrate leaf epidermal cells. We demonstrated that our
      method detected the gene expression of both the host plant and pathogen
      simultaneously in the same infected leaf blades in natural infection conditions
      without any artificial treatments. The upregulation of 240 fungal transcripts
      encoding putative secreted proteins was observed, suggesting that these
      candidates of fungal effector genes may play important roles in initial infection
      processes. The upregulation of transcripts encoding glycosyl hydrolases,
      cutinases and LysM domain-containing proteins were observed in the blast fungus,
      whereas pathogenesis-related and phytoalexin biosynthetic genes were upregulated
      in rice. Furthermore, more drastic changes in expression were observed in the
      incompatible interactions compared with the compatible ones in both rice and
      blast fungus at this stage. Our mixed transcriptome analysis is useful for the
      simultaneous elucidation of the tactics of host plant defense and pathogen
      attack.

PMID- 23139847
TI  - Discrepancies in Adolescents' and their Mothers' Perceptions of the Family and
      Adolescent Externalizing Problems.
AB  - The goal of this study was to examine whether adolescent-mother discrepancies in
      perceptions of the family predict later adolescent externalizing problems and/or
      whether adolescent externalizing problems predict later adolescent-mother
      discrepancies in perceptions of the family. In the spring of 2007 (Time 1) and
      2008 (Time 2), surveys were administered to 125 15-18 year-old adolescent and
      their mothers. SEM results indicated that greater discrepancies in adolescent
      mother perceptions of the family predicted higher levels of adolescent
      externalizing symptomatology (as reported by both adolescents and their mothers).
      In contrast, higher levels of externalizing symptomatology did not predict later
      discrepancies in adolescent-mother perceptions of the family. These findings
      suggest that research on adolescent adjustment should not solely rely on
      perceptions of the adolescent. In addition, the results highlight the importance
      of taking both directions of effect into consideration when examining the family
      and adolescent adjustment.

PMID- 23139848
TI  - Clinical features of recurrent stroke after intracerebral hemorrhage.
AB  - There have been many reports about the prognosis and risk factors of stroke
      recurrence following brain infarction (BI). However, little is known about the
      stroke recurrence after primary intracerebral hemorrhage (PICH). Therefore, we
      explored the recurrent stroke patients after initial PICH retrospectively, to
      reveal the critical factors of stroke recurrence. Acute BI (n=4013) and acute
      PICH patients (n=1067) admitted to the hospital between April 2000 and March 2009
      were consecutively screened. PICH patients with a history of ICH and BI patients
      with a history of ICH were then classified into the ICH-ICH group (n=64, age
      70.8+/-9.5 years) and ICH-BI group (n=52, age 72.8+/-9.7years), respectively. ICH
      lesions were categorized into ganglionic and lober types according to the brain
      magnetic resonance imaging. Subtypes of BI were classified into cardioembolism,
      large-artery atherosclerosis, small-artery occlusion and others. There was no
      difference in incidence of risk factors between ICH-ICH and ICH-BI groups.
      Distribution of initial PICH lesions was significantly abundant in the lobar type
      in the ICH-ICH group (P<0.01) and in ganglionic type in the ICH-BI group
      (P<0.02). Age of onset was significantly older in recurrent lobar ICH compared
      with recurrent ganglionic ICH (P<0.01: 73.6+/-10.0 and 59.1+/-9.0 years,
      respectively). In conclusion, ganglionic ICH patients may have a chance of
      recurrent stroke in both brain infarction and ganglionic ICH, suggesting the
      participation of atherosclerosis in intracranial arteries. Lobar ICH patients
      were older and prone to recurrent lobar ICH, suggesting the participation of
      cerebral amyloid angiopathy as a risk of stroke recurrence.

PMID- 23139849
TI  - Airborne pollutants and lacunar stroke: a case cross-over analysis on stroke unit
      admissions.
AB  - Particulate air pollution is known to be associated with cardiovascular disease.
      The relation of particulate air pollution with cerebrovascular disease (CVD) has
      not been extensively studied, particularly in relation to different subtypes of
      stroke. A time-series study was conducted to evaluate the association between
      daily air pollution and acute stroke unit hospitalizations in Mantua, Italy. We
      analyzed 781 CVD consecutive patients living in Mantua county admitted between
      2006-08. Data on stroke types, demographic variables, risk factors were available
      from the Lombardia Stroke Registry. Daily mean value of particulate matter with a
      diameter <10 um (PM(10)), carbon monoxide, nitric oxide, nitrogen dioxide,
      sulphur dioxide, benzene and ozone were used in the analysis. The association
      between CVD, ischemic strokes subtypes and pollutants was investigated with a
      case-crossover design, using conditional logistic regression analysis, adjusting
      for temperature, humidity, barometric pressure and holidays. Among the 781
      subjects admitted 75.7% had ischemic stroke, 11.7% haemorrhagic stroke 12.6%
      transient ischemic attack. In men admission for stroke was associated with PM(10)
      [odds ratio (OR) 1.01, 95%; confidence interval (CI) 1.00-1.02; P<0.05].
      According to the clinical classification, lacunar anterior circulation syndrome
      stroke type was related to PM(10) level registered on the day of admission for
      both genders (OR: 1.01, 95%; CI: 1.00-1.02; P<0.05) while for total anterior
      circulation syndrome stroke only in men (OR: 1.04, 95%; CI 1.01-1.07; P<0.05).In
      conclusion, our study confirms that air pollution peaks may contribute to
      increase the risk of hospitalization for stroke and particulate matter seems to
      be a significant risk factor, especially for lacunar stroke.

PMID- 23139850
TI  - Recurrent syncope in a hypertensive subject with vascular cognitive impairment
      and permanent pacemaker.
AB  - Syncope following permanent pacemaker (PM) implantation is a nightmare for
      electrophysiologists. We describe a case of daily recurrent syncope in an 84-year
      old man having a dual-chamber pacemaker implanted for complete atrio-ventricular
      block occurred 4 years before the admission to our department. He had a history
      of arterial hypertension, parossistic atrial fibrillation, chronic obstructive
      pulmonary disease, stage-III chronic renal failure, mild vascular cognitive
      impairment and glaucoma. The initial work-up including electrocardiogram (ECG),
      repeated PM interrogations, Holter electrocardiogram, blood pressure measurement
      in orthostatic position, complete blood count, serum glycaemia, electrolytes and
      thyroid function tests showed normal findings. Syncope occurred in lying position
      and during 90 degrees  left clockwise neck rotation and was associated to pallor,
      sweating, tonic-clonic seizures and transient self-limited loss of consciousness
      lasting a few seconds. Electroencephalogram was normal. During continuous ECG
      monitoring, the right rotation of the head determined a ventricular asystolic
      pause lasting 9 seconds associated with loss of consciousness. Restoration of
      sinus rhythm was observed after bringing back the head in axis. The PM
      interrogation, performed during pacing failure, recorded low impedance of bipolar
      ventricular lead, suggesting a damage in lead insulation. It is likely that lead
      movements during clockwise neck rotation produced an intermittent short circuit
      that prevented sufficient energy delivery to the myocardium with a consequence of
      sudden loss of capture.

PMID- 23139852
TI  - Functional influence of botulinum neurotoxin type A treatment (Xeomin(r)) of
      multifocal upper and lower limb spasticity on chronic hemiparetic gait.
AB  - This report describes the modification of hemiplegic shoulder pain and walking
      velocity through injections of Xeomin(r), a new botulinum neurotoxin type A
      formulation, in a 67-year-old woman with chronic residual left hemiparesis and
      hemiparetic gait attributable to stroke. Clinical evaluation included upper and
      lower limb spasticity, upper and lower limb pain, trunk control, upper and lower
      limb motricity index, visual gait analysis, and gait velocity. Assessments were
      performed before, 1 week after, and 1 month after treatment. Improvement was
      observed in all clinical parameters assessed. Amelioration of spasticity of the
      upper and lower limbs and shoulder pain was observed after 1 month. Trunk
      postural attitude and paraxial muscle recruitment recovered. No adverse events
      were observed and the patient shows significant improvement of functional
      impairment derived from chronic spasticity after treatment with Xeomin(r). We
      also provide a simple and useful protocol for clinical evaluation of the
      treatment.

PMID- 23139851
TI  - Vascular incontinence: incontinence in the elderly due to ischemic white matter
      changes.
AB  - This review article introduces the new concept of vascular incontinence, a
      disorder of bladder control resulting from cerebral white matter disease (WMD).
      The concept is based on the original observation in 1999 of a correlation between
      the severity of leukoareosis or WMD, urinary symptoms, gait disorder and
      cognitive impairment. Over the last 20 years, the realization that WMD is not a
      benign incidental finding in the elderly has become generally accepted and
      several studies have pointed to an association between geriatric syndromes and
      this type of pathology. The main brunt of WMD is in the frontal regions, a region
      recognized to be crucial for bladder control. Other disorders should be excluded,
      both neurological and urological, such as normal-pressure hydrocephalus,
      progressive supranuclear palsy, etc., and prostatic hyperplasia, physical stress
      incontinence, nocturnal polyuria, etc. Treatment involves management of small
      vessel disease risk factors and anticholinergic drugs that do not easily
      penetrate the blood brain barrier to improve bladder control.

PMID- 23139853
TI  - Outcome after systemic thrombolysis is predicted by age and stroke severity: an
      open label experience with recombinant tissue plasminogen activator and
      tirofiban.
AB  - Stroke patients can recover upon intravenous thrombolysis but remain impaired in
      lacking recanalization. We sought to investigate the clinical effect of systemic
      thrombolysis with an intravenous bolus of 20 mg recombinant tissue plasminogen
      activator (rtPA) and an infusion of body-weight adjusted tirofiban for 48 hours
      in acute stroke. This prospective, open label study, included 192 patients (68+/
      13 years, 50% males) treated between 1 January 2005 and 31 December 2007. The
      neurological deficit was assessed with the National Institutes of Health stroke
      scale (NIHSS). Follow-up was performed using a telephone interview of modified
      Rankin Scale (mRS) and Barthel index. The site of cerebral artery occlusion was
      determined by computed tomography or magnetic resonance angiography. Data were
      analyzed by descriptive statistics and multiple regression analyses. Eighty-one
      percent of the patients had an infarct in the middle cerebral artery (MCA)
      territory and were severely affected with a median NIHSS of 10. During treatment
      on the Stroke Unit the patients improved (P<0.0001) except for patients who
      deceased due to malignant infarction (n=10) or cerebral haemorrhage (n=6); 18
      percent deceased within 100 days which was predicted by older age (76 + 10 years,
      P<0.05) and more severe affection on admission (P<0.0001). Also, these patients
      more frequently had atrial fibrillation (P<0.03) than the surviving patients. The
      surviving patients had more frequently distal MCA occlusions and improved further
      (P<0.0001). At follow-up 48% of the patients had a mRS of 0 and 1. Similarly to
      intravenous thrombolysis with body-weight adjusted rtPA, poor prognosis was
      predicted by higher age, more severe neurological deficit at stroke admission,
      and a proximal MCA occlusion. Half of the surviving patients improved to no or
      minimal impairment.

PMID- 23139855
TI  - Permuting Diels-Alder and Robinson Annulation Stereopatterns.
AB  - Controlled isomerization of the double bond of certain Diels-Alder reactions
      provides substrates that, upon oxidation, give rise to products whose gross
      structure corresponds to that of a Robinson annulation. In these cases, the
      stereochemistry of the Robinson annulation product reflects the fact that the
      initial combination occurred in a Diels-Alder mode. Using these principles, we
      have synthesized carissone and cosmosoic acid. In the latter case, our total
      synthesis raised serious questions as to the accuracy of the assigned structure
      of the natural product.

PMID- 23139854
TI  - A Programmable Transducer Self-Assembled from DNA.
AB  - A transducer consists of an input/output alphabet, a finite set of states, and a
      transition function. From an input symbol applied to a given state, the
      transition function determines the next state, and an output symbol. Using DNA,
      we have constructed a transducer that divides a number by 3. The input consists
      of a series of individually addressable 2-state DNA nanomechanical devices that
      control the orientations of a group of flat 6-helix DNA motifs; these motifs have
      edge domains tailed in sticky ends corresponding to the numbers 0 and 1. Three
      domain DNA molecules (TX tiles) act as computational tiles that correspond to the
      transitions that the transducer can undergo. The output domain of these TX tiles
      contains sticky ends that also correspond to 0 or 1. Two different DNA tiles can
      chelate these output domains: A 5 nm gold nanoparticle is attached to the
      chelating tile that binds to 0-domains and a 10 nm gold nanoparticle is attached
      to the chelating tile that binds to 1-domains. The answer to the division is
      represented by the series of gold nanoparticles, which can be interpreted as a
      binary number. The answers of the computation are read out by examination of the
      transducer complexes under a transmission electron microscope. The start or end
      points of the output sequence can be indicated by the presence of a 15 nm gold
      nanoparticle. This work demonstrates two previously unreported features
      integrated in a single framework: [1] a system that combines DNA algorithmic self
      assembly with DNA nanomechanical devices that control that input, and [2] the
      arrangement of non-DNA species, here metallic nanoparticles, through DNA
      algorithmic self-assembly. The nanomechanical devices are controlled by single
      stranded DNA strands, allowing multiple input sequences to be applied to the rest
      of the system, thus guiding the algorithmic self-assembly to a variety of
      outputs.

PMID- 23139856
TI  - Developing an international network for Alzheimer research: The Dominantly
      Inherited Alzheimer Network.
AB  - The Dominantly Inherited Alzheimer Network (DIAN) is a collaborative effort of
      international Alzheimer disease (AD) centers that are conducting a multifaceted
      prospective biomarker study in individuals at-risk for autosomal dominant AD
      (ADAD). DIAN collects comprehensive information and tissue in accordance with
      standard protocols from asymptomatic and symptomatic ADAD mutation carriers and
      their non-carrier family members to determine the pathochronology of clinical,
      cognitive, neuroimaging, and fluid biomarkers of AD. This article describes the
      structure, implementation, and underlying principles of DIAN, as well as the
      demographic features of the initial DIAN cohort.

PMID- 23139857
TI  - Characterisation of the organophosphate hydrolase catalytic activity of SsoPox.
AB  - SsoPox is a lactonase endowed with promiscuous phosphotriesterase activity
      isolated from Sulfolobus solfataricus that belongs to the Phosphotriesterase-Like
      Lactonase family. Because of its intrinsic thermal stability, SsoPox is seen as
      an appealing candidate as a bioscavenger for organophosphorus compounds. A
      comprehensive kinetic characterisation of SsoPox has been performed with various
      phosphotriesters (insecticides) and phosphodiesters (nerve agent analogues) as
      substrates. We show that SsoPox is active for a broad range of OPs and remains
      active under denaturing conditions. In addition, its OP hydrolase activity is
      highly stimulated by anionic detergent at ambient temperature and exhibits
      catalytic efficiencies as high as k(cat)/K(M) of 10(5) M(-1)s(-1) against a nerve
      agent analogue. The structure of SsoPox bound to the phosphotriester
      fensulfothion reveals an unexpected and non-productive binding mode. This feature
      suggests that SsoPox's active site is sub-optimal for phosphotriester binding,
      which depends not only upon shape but also on localised charge of the ligand.

PMID- 23139858
TI  - Loss of the respiratory enzyme citrate synthase directly links the Warburg effect
      to tumor malignancy.
AB  - To investigate whether altered energy metabolism induces the Warburg effect and
      results in tumor malignancy, the respiratory enzyme citrate synthase (CS) was
      examined, silenced, and the effects analyzed. In human cervical carcinoma cells,
      RNAi-mediated CS knockdown induced morphological changes characteristic of the
      epithelial-mesenchymal transition (EMT). This switch accelerated cancer cell
      metastasis and proliferation in in vitro assays and in vivo tumor xenograft
      models. Notably, CS knockdown cells exhibited severe defects in respiratory
      activity and marked decreases in ATP production, but great increases in
      glycolytic metabolism. This malignant progression was due to activation of EMT
      related regulators; altered energy metabolism resulted from deregulation of the
      p53/TIGAR and SCO2 pathways. This phenotypic change was completely reversed by
      p53 reactivation via treatment with proteasome inhibitor MG132 or co-knockdown of
      E3 ligase HDM2 and partially suppressed by ATP treatment. This study directly
      links the Warburg effect to tumor malignancy via induction of the EMT phenotype.

PMID- 23139859
TI  - Formylpeptide receptors are critical for rapid neutrophil mobilization in host
      defense against Listeria monocytogenes.
AB  - Listeria monocytogenes (Listeria) causes opportunistic infection in
      immunocompromised hosts with high mortality. Resistance to Listeria depends on
      immune responses and recruitment of neutrophils of the immune system into
      infected sites is an early and critical step. Mouse neutrophils express two G
      protein-coupled formylpeptide receptor subtypes Fpr1 and Fpr2 that recognize
      bacterial and host-derived chemotactic molecules including Listeria peptides for
      cell migration and activation. Here we report deficiency in Fprs exacerbated the
      severity of the infection and increased the mortality of infected mice. The
      mechanism involved impaired early neutrophil recruitment to the liver with Fpr1
      and Fpr2 being sole receptors for neutrophils to sense Listeria chemoattractant
      signals and for production of bactericidal superoxide. Thus, Fprs are essential
      sentinels to guide the first wave of neutrophil infiltration in the liver of
      Listeria-infected mice for effective elimination of the invading pathogen.

PMID- 23139860
TI  - Inexpensive method for producing macroporous silicon particulates (MPSPs) with
      pyrolyzed polyacrylonitrile for lithium ion batteries.
AB  - One of the most exciting areas in lithium ion batteries is engineering structured
      silicon anodes. These new materials promise to lead the next generation of
      batteries with significantly higher reversible charge capacity than current
      technologies. One drawback of these materials is that their production involves
      costly processing steps, limiting their application in commercial lithium ion
      batteries. In this report we present an inexpensive method for synthesizing
      macroporous silicon particulates (MPSPs). After being mixed with
      polyacrylonitrile (PAN) and pyrolyzed, MPSPs can alloy with lithium, resulting in
      capacities of 1000 mAhg(-1) for over 600+ cycles. These sponge-like MPSPs with
      pyrolyzed PAN (PPAN) can accommodate the large volume expansion associated with
      silicon lithiation. This performance combined with low cost processing yields a
      competitive anode material that will have an immediate and direct application in
      lithium ion batteries.

PMID- 23139862
TI  - There is more than a power law in Zipf.
AB  - The largest cities, the most frequently used words, the income of the richest
      countries, and the most wealthy billionaires, can be all described in terms of
      Zipf's Law, a rank-size rule capturing the relation between the frequency of a
      set of objects or events and their size. It is assumed to be one of many
      manifestations of an underlying power law like Pareto's or Benford's, but
      contrary to popular belief, from a distribution of, say, city sizes and a simple
      random sampling, one does not obtain Zipf's law for the largest cities. This
      pathology is reflected in the fact that Zipf's Law has a functional form
      depending on the number of events N. This requires a fundamental property of the
      sample distribution which we call 'coherence' and it corresponds to a 'screening'
      between various elements of the set. We show how it should be accounted for when
      fitting Zipf's Law.

PMID- 23139861
TI  - ROCK/Cdc42-mediated microglial motility and gliapse formation lead to
      phagocytosis of degenerating dopaminergic neurons in vivo.
AB  - The role of microglial motility in the context of adult neurodegeneration is
      poorly understood. In the present work, we investigated the microanatomical
      details of microglia-neuron interactions in an experimental mouse model of
      Parkinson's disease following the intraperitoneal injection of MPTP. The specific
      intoxication of dopaminergic neurons induces the cellular polarization of
      microglia, leading to the formation of body-to-body neuron-glia contacts, called
      gliapses, which precede neuron elimination. Inhibiting ROCK/Cdc42-mediated
      microglial motility in vivo blocks the activating features of microglia, such as
      increased cell size and number of filopodia and diminishes their
      phagocyting/secreting domains, as the reduction of the Golgi apparatus and the
      number of microglia-neuron contacts has shown. High-resolution confocal images
      and three-dimensional rendering demonstrate that microglia engulf entire neurons
      at one-to-one ratio, and the microglial cell body participates in the formation
      of the phagocytic cup, engulfing and eliminating neurons in areas of dopaminergic
      degeneration in adult mammals.

PMID- 23139863
TI  - Modular networks of word correlations on Twitter.
AB  - Complex networks are important tools for analyzing the information flow in many
      aspects of nature and human society. Using data from the microblogging service
      Twitter, we study networks of correlations in the occurrence of words from three
      different categories, international brands, nouns and US major cities. We create
      networks where the strength of links is determined by a similarity measure based
      on the rate of co-occurrences of words. In comparison with the null model, where
      words are assumed to be uncorrelated, the heavy-tailed distribution of pair
      correlations is shown to be a consequence of groups of words representing similar
      entities.

PMID- 23139864
TI  - In science "there is no bad publicity": papers criticized in comments have high
      scientific impact.
AB  - Comments are special types of publications whose aim is to correct or criticize
      previously published papers. For this reason, comments are believed to make
      commented papers less worthy or trusty to the eyes of the scientific community,
      and thus predestined to have low scientific impact. Here, we show that such
      belief is not supported by empirical evidence. We consider thirteen major
      publication outlets in science, and perform systematic comparisons between the
      citations accumulated by commented and non commented articles. We find that (i)
      commented papers are, on average, much more cited than non commented papers, and
      (ii) commented papers are more likely to be among the most cited papers of a
      journal. Since comments are published soon after criticized papers, comments
      should be viewed as early indicators of the future impact of criticized papers.

PMID- 23139865
TI  - A real-time dynamic holographic material using a fast photochromic molecule.
AB  - We have developed a real-time, dynamic holographic material that exhibits rapid
      colouration upon irradiation with UV light and successive fast thermal bleaching
      within tens of milliseconds at room temperature. Photochromic polymer films were
      prepared by a simple solution-casting method from the benzene solution of the
      mixture of the photochromic molecule, poly(ethyl acrylate), and poly(phenoxyethyl
      acrylate). The real-time control of holographic images using the photochromic
      polymer film yields a speed equivalent to the time resolution of the human eye.
      This new type of dynamic holographic material based on fast photochromism opens
      up an exciting new area of research in the future development of a large dynamic
      3D display.

PMID- 23139866
TI  - Targeted transcript profiling by sequencing.
AB  - In this work we present a targeted gene expression strategy employing
      trinucleotide threading (TnT) amplification and massive parallel sequencing. We
      have previously shown that TnT combined with array readout accurately monitors
      expression levels. However, with this detection strategy spurious products go
      undetected. Accordingly, we adapted the TnT protocol to massive parallel
      sequencing to acquire an unbiased view of the entire TnT-generated product
      population. In this manner we investigated the identity of undesired products,
      their extent at different oligonucleotide:RNA ratios and their effect on the
      expression levels. We demonstrate that TnT gene expression profiling with massive
      sequencing readout renders reliable expression data from as low as 3.5 ng of
      total RNA. Moreover, using 350 ng of total RNA results in only 0.7% to 1.1%
      undesired products. When lowering the amount of input material, the undesired
      product fraction increases but this does not influence the expression profiles.

PMID- 23139867
TI  - RRM2B suppresses activation of the oxidative stress pathway and is up-regulated
      by p53 during senescence.
AB  - RRM2B is the DNA damage-inducible small subunit of ribonucleotide reductase, the
      rate-limiting enzyme in de novo deoxyribonucleoside triphosphate synthesis.
      Although RRM2B is implicated in DNA repair and the maintenance of mitochondrial
      DNA content, the regulation and function of RRM2B in senescence have not been
      previously established. Here, we show that RRM2B is highly induced in a p53
      dependent manner during senescence in primary human fibroblast IMR90 cells and is
      expressed at higher levels in senescent precancerous human prostatic
      intraepithelial neoplasm lesions compared to adjacent normal prostate glands.
      Paradoxically, silencing RRM2B expression leads to an increase in the level of
      reactive oxygen species, mitochondrial membrane depolarization, and premature
      senescence in a p38MAPK- and p53-dependent manner in young fibroblasts.
      Consistently, induction of senescence is accelerated in Rrm2b deficient mouse
      embryo fibroblasts. Our data demonstrate that RRM2B is induced by stress signals
      prior to the onset of senescence and prevents premature oxidative stress-induced
      senescence.

PMID- 23139868
TI  - A chemical genomic study identifying diversity in cell migration signaling in
      cancer cells.
AB  - The aim of this study was to analyze the diversity and consistency of regulatory
      signaling in cancer cell migration, using a chemical genomic approach. The
      effects of 34 small molecular compounds were assessed quantitatively by wound
      healing assay in ten types of migrating cells. Hierarchical clustering was
      performed on the subsequent migration inhibition profile of the compounds and
      cancer cell types. The result was that hierarchical clustering accurately
      classified the compounds according to their targets. Furthermore, the cancer
      cells tested in this study were classified into three clusters, and the compounds
      were grouped into four clusters. An inhibitor of JNK suppressed all types of cell
      migration; however, inhibitors of ROCK, GSK-3 and p38MAPK only inhibited the
      migration of a subset of cell lines. Thus, our analytical system could easily
      distinguish between the common and cell type-specific signals responsible for
      cell migration.

PMID- 23139869
TI  - A functioning artificial secretory cell.
AB  - We present an amperometric study of content release from individual vesicles in
      an artificial secretory cell designed with the minimal components required to
      carry out exocytosis. Here, the membranes of the cell and vesicles are
      substituted for protein-free giant and large unilamellar vesicles respectively.
      In replacement of the SNARE-complex, the cell model was equipped with an analog
      composed of complimentary DNA constructs. The DNA constructs hybridize in a
      zipper-like fashion to bring about docking of the artificial secretory vesicles
      and following the addition of Ca(2+ )artificial exocytosis was completed.
      Exocytotic events recorded from the artificial cell closely approximate
      exocytosis in live cells. The results together with simulations of vesicular
      release demonstrate that the molecular flux in this model is attenuated and we
      suggest that this is the result of restricted diffusion through a semi-stable
      fusion pore or a partitioning of the signalling molecule out of the fused vesicle
      membrane.

PMID- 23139870
TI  - Genetic diversity is positively associated with fine-scale momentary abundance of
      an invasive ant.
AB  - Many introduced species become invasive despite genetic bottlenecks that should,
      in theory, decrease the chances of invasion success. By contrast, population
      genetic bottlenecks have been hypothesized to increase the invasion success of
      unicolonial ants by increasing the genetic similarity between descendent
      populations, thus promoting co-operation. We investigated these alternate
      hypotheses in the unicolonial yellow crazy ant, Anoplolepis gracilipes, which has
      invaded Arnhem Land in Australia's Northern Territory. We used momentary
      abundance as a surrogate measure of invasion success, and investigated the
      relationship between A. gracilipes genetic diversity and its abundance, and the
      effect of its abundance on species diversity and community structure. We also
      investigated whether selected habitat characteristics contributed to differences
      in A. gracilipes abundance, for which we found no evidence. Our results revealed
      a significant positive association between A. gracilipes genetic diversity and
      abundance. Invaded communities were less diverse and differed in structure from
      uninvaded communities, and these effects were stronger as A. gracilipes abundance
      increased. These results contradict the hypothesis that genetic bottlenecks may
      promote unicoloniality. However, our A. gracilipes study population has diverged
      since its introduction, which may have obscured evidence of the bottleneck that
      would likely have occurred on arrival. The relative importance of genetic
      diversity to invasion success may be context dependent, and the role of genetic
      diversity may be more obvious in the absence of highly favorable novel ecological
      conditions.

PMID- 23139871
TI  - Sequence polymorphisms in wild, weedy, and cultivated rice suggest seed
      shattering locus sh4 played a minor role in Asian rice domestication.
AB  - The predominant view regarding Asian rice domestication is that the initial
      origin of nonshattering involved a single gene of large effect, specifically, the
      sh4 locus via the evolutionary replacement of a dominant allele for shattering
      with a recessive allele for reduced shattering. Data have accumulated to
      challenge this hypothesis. Specifically, a few studies have reported occasional
      seed-shattering plants from populations of the wild progenitor of cultivated rice
      (Oryza rufipogon complex) being homozygous for the putative "nonshattering" sh4
      alleles. We tested the sh4 hypothesis for the domestication of cultivated rice by
      obtaining genotypes and phenotypes for a diverse set of samples of wild, weedy,
      and cultivated rice accessions. The cultivars were fixed for the putative
      "nonshattering" allele and nonshattering phenotype, but wild rice accessions are
      highly polymorphic for the putative "nonshattering" allele (frequency ~26%) with
      shattering phenotype. All weedy rice accessions are the "nonshattering" genotype
      at the sh4 locus but with shattering phenotype. These data challenge the widely
      accepted hypothesis that a single nucleotide mutation ("G"/"T") of the sh4 locus
      is the major driving force for rice domestication. Instead, we hypothesize that
      unidentified shattering loci are responsible for the initial domestication of
      cultivated rice through reduced seed shattering.

PMID- 23139872
TI  - Population structure of the butternut canker fungus, Ophiognomonia clavigignenti
      juglandacearum, in North American forests.
AB  - The occurrence of multiple introduction events, or sudden emergence from a host
      jump, of forest pathogens may be an important factor in successful establishment
      in a novel environment or on a new host; however, few studies have focused on the
      introduction and emergence of fungal pathogens in forest ecosystems. While
      Ophiognomonia clavigignenti-juglandacearum (Oc-j), the butternut canker fungus,
      has caused range-wide mortality of butternut trees in North America since its
      first observation in 1967, the history of its emergence and spread across the
      United States and Canada remains unresolved. Using 17 single nucleotide
      polymorphic loci, we investigated the genetic population structure of 101
      isolates of Oc-j from across North America. Clustering analysis revealed that the
      Oc-j population in North America is made up of three differentiated genetic
      clusters of isolates, and these genetic clusters were found to have a strong
      clonal structure. These results, in combination with the geographic distribution
      of the populations, suggest that Oc-j was introduced or has emerged in North
      America on more than one occasion, and these clonal lineages have since
      proliferated across much of the range of butternut. No evidence of genetic
      recombination was observed in the linkage analysis, and conservation of the
      distinct genetic clusters in regions where isolates from two or more genetic
      clusters are present, would indicate a very minimal or non-existent role of
      sexual recombination in populations of Oc-j in North America.

PMID- 23139873
TI  - Canid hybridization: contemporary evolution in human-modified landscapes.
AB  - Contemporary evolution through human-induced hybridization occurs throughout the
      taxonomic range. Formerly allopatric species appear especially susceptible to
      hybridization. Consequently, hybridization is expected to be more common in
      regions with recent sympatry owing to human activity than in areas of historical
      range overlap. Coyotes (Canis latrans) and gray wolves (C. lupus) are
      historically sympatric in western North America. Following European settlement
      gray wolf range contracted, whereas coyote range expanded to include eastern
      North America. Furthermore, wolves with New World (NW) mitochondrial DNA (mtDNA)
      haplotypes now extend from Manitoba to Quebec in Canada and hybridize with gray
      wolves and coyotes. Using mtDNA and 12 microsatellite markers, we evaluated
      levels of wolf-coyote hybridization in regions where coyotes were present (the
      Canadian Prairies, n = 109 samples) and absent historically (Quebec, n = 154).
      Wolves with NW mtDNA extended from central Saskatchewan (51 degrees N, 69 degrees
      W) to northeastern Quebec (54 degrees N, 108 degrees W). On the Prairies, 6.3% of
      coyotes and 9.2% of wolves had genetic profiles suggesting wolf-coyote
      hybridization. In contrast, 12.6% of coyotes and 37.4% of wolves in Quebec had
      profiles indicating hybrid origin. Wolves with NW and Old World (C. lupus) mtDNA
      appear to form integrated populations in both regions. Our results suggest that
      hybridization is more frequent in historically allopatric populations. Range
      shifts, now expected across taxa following climate change and other human
      influence on the environment, might therefore promote contemporary evolution by
      hybridization.

PMID- 23139874
TI  - Diversifying and correlational selection on behavior toward conspecific and
      heterospecific competitors in brook stickleback (Culaea inconstans).
AB  - Behaviors toward heterospecifics and conspecifics may be correlated because of
      shared mechanisms of expression in both social contexts (nonadaptive covariation)
      or because correlational selection favors adaptive covariation. We evaluated
      these hypotheses by comparing behavior toward conspecifics and heterospecifics in
      brook stickleback (Culaea inconstans) from three populations sympatric with and
      three allopatric from a competitor, the ninespine stickleback (Pungitius
      pungitius). Behavioral traits were classified into three multivariate components:
      overt aggression, sociability, and activity. The correlation of behavior between
      social contexts for both overt aggression and activity varied among populations
      in a way unrelated to sympatry with ninespine stickleback, while mean aggression
      was reduced in sympatry. Correlations in allopatric populations suggest that
      overt aggression and activity may genetically covary between social contexts for
      nonadaptive reasons. Sociability was rarely correlated in allopatry but was
      consistently correlated in sympatry despite reduced mean sociability, suggesting
      that correlational selection may favor a sociability syndrome in brook
      stickleback when they coexist with ninespine stickleback. Thus, interspecific
      competition may impose diversifying selection on behavior among populations,
      although the causes of correlated behavior toward conspecifics and
      heterospecifics and whether it can evolve in one social context independent of
      the other may depend on the type of behavior.

PMID- 23139875
TI  - Age-specific oxidative status and the expression of pre- and postcopulatory
      sexually selected traits in male red junglefowl, Gallus gallus.
AB  - Oxidative stress is emerging as a key factor underpinning life history and the
      expression of sexually selected traits. Resolving the role of oxidative stress in
      life history and sexual selection requires a pluralistic approach, which
      investigates how age affects the relationship between oxidative status (i.e.,
      antioxidants and oxidative damage) and the multiple traits contributing to
      variation in reproductive success. Here, we investigate the relationship between
      oxidative status and the expression of multiple sexually selected traits in two
      age classes of male red junglefowl, Gallus gallus, a species which displays
      marked male reproductive senescence. We found that, irrespective of male age,
      both male social status and comb size were strongly associated with plasma
      oxidative status, and there was a nonsignificant tendency for sperm motility to
      be associated with seminal oxidative status. Importantly, however, patterns of
      plasma and seminal antioxidant levels differed markedly in young and old males.
      While seminal antioxidants increased with plasma antioxidants in young males, the
      level of seminal antioxidants remained low and was independent of plasma levels
      in old males. In addition, old males also accumulated more oxidative damage in
      their sperm DNA. These results suggest that antioxidant allocation across
      different reproductive traits and somatic maintenance might change drastically as
      males age, leading to age-specific patterns of antioxidant investment.

PMID- 23139876
TI  - Specialization in habitat use by coral reef damselfishes and their susceptibility
      to habitat loss.
AB  - While it is generally assumed that specialist species are more vulnerable to
      disturbance compared with generalist counterparts, this has rarely been tested in
      coastal marine ecosystems, which are increasingly subject to a wide range of
      natural and anthropogenic disturbances. Habitat specialists are expected to be
      more vulnerable to habitat loss because habitat availability exerts a greater
      limitation on population size, but it is also possible that specialist species
      may escape effects of disturbance if they use habitats that are generally
      resilient to disturbance. This study quantified specificity in use of different
      coral species by six coral-dwelling damselfishes (Chromis viridis, C.
      atripectoralis, Dascyllus aruanus, D. reticulatus, Pomacentrus moluccensis, and
      P. amboinensis) and related habitat specialization to proportional declines in
      their abundance following habitat degradation caused by outbreaks of the coral
      eating starfish, Acanthaster planci. The coral species preferred by most coral
      dwelling damselfishes (e.g., Pocillopora damicornis) were frequently consumed by
      coral eating crown-of-thorns starfish, such that highly specialized damselfishes
      were disproportionately affected by coral depletion, despite using a narrower
      range of different coral species. Vulnerability of damselfishes to this
      disturbance was strongly correlated with both their reliance on corals and their
      degree of habitat specialization. Ongoing disturbances to coral reef ecosystems
      are expected, therefore, to lead to fundamental shifts in the community structure
      of fish communities where generalists are favored over highly specialist species.

PMID- 23139877
TI  - Cascading trait-mediated interactions induced by ant pheromones.
AB  - Trait-mediated indirect interactions (TMII) can be as important as density
      mediated indirect interactions. Here, we provide evidence for a novel trait
      mediated cascade (where one TMII affects another TMII) and demonstrate that the
      mechanism consists of a predator eavesdropping on chemical signaling. Ants
      protect scale insects from predation by adult coccinellid beetles - the first
      TMII. However, parasitic phorid flies reduce ant foraging activity by 50% - the
      second TMII, providing a window of opportunity for female beetles to oviposit in
      high-quality microsites. Beetle larvae are protected from ant predation and
      benefit from living in patches with high scale densities. We demonstrate that
      female beetles can detect pheromones released by the ant when attacked by
      phorids, and that only females, and especially gravid females, are attracted to
      the ant pheromone. As ants reduce their movement when under attack by phorids, we
      conclude that phorids facilitate beetle oviposition, thus producing the TMII
      cascade.

PMID- 23139878
TI  - Contemporary ocean warming and freshwater conditions are related to later sea age
      at maturity in Atlantic salmon spawning in Norwegian rivers.
AB  - Atlantic salmon populations are reported to be declining throughout its range,
      raising major management concerns. Variation in adult fish abundance may be due
      to variation in survival, growth, and timing of life history decisions. Given the
      complex life history, utilizing highly divergent habitats, the reasons for
      declines may be multiple and difficult to disentangle. Using recreational angling
      data of two sea age groups, one-sea-winter (1SW) and two-sea-winter (2SW) fish
      originated from the same smolt year class, we show that sea age at maturity of
      the returns has increased in 59 Norwegian rivers over the cohorts 1991-2005. By
      means of linear mixed-effects models we found that the proportion of 1SW fish
      spawning in Norway has decreased concomitant with the increasing sea surface
      temperature experienced by the fish in autumn during their first year at sea.
      Furthermore, the decrease in the proportion of 1SW fish was influenced by
      freshwater conditions as measured by water discharge during summer months 1 year
      ahead of seaward migration. These results suggest that part of the variability in
      age at maturity can be explained by the large-scale changes occurring in the
      north-eastern Atlantic pelagic food web affecting postsmolt growth, and by
      differences in river conditions influencing presmolt growth rate and later
      upstream migration.

PMID- 23139879
TI  - Reduced predation risk for melanistic pygmy grasshoppers in post-fire
      environments.
AB  - The existence of melanistic (black) color forms in many species represents
      interesting model systems that have played important roles for our understanding
      of selective processes, evolution of adaptations, and the maintenance of
      variation. A recent study reported on rapid evolutionary shifts in frequencies of
      the melanistic forms in replicated populations of Tetrix subulata pygmy
      grasshoppers; the incidence of the melanistic form was higher in recently burned
      areas with backgrounds blackened by fire than in nonburned areas, and it declined
      over time in postfire environments. Here, we tested the hypothesis that the
      frequency shifts of the black color variant were driven, at least in part, by
      changes in the selective regime imposed by visual predators. To study
      detectability of the melanistic form, we presented human "predators" with images
      of black grasshoppers and samples of the natural habitat on computer screens. We
      demonstrate that the protective value of black coloration differs between burnt
      and nonburnt environments and gradually increases in habitats that have been more
      blackened by fire. These findings support the notion that a black color pattern
      provides improved protection from visually oriented predators against blackened
      backgrounds and implicate camouflage and predation as important drivers of fire
      melanism in pygmy grasshoppers.

PMID- 23139880
TI  - Homoploid hybrid origin of Yucca gloriosa: intersectional hybrid speciation in
      Yucca (Agavoideae, Asparagaceae).
AB  - There is a growing appreciation for the importance of hybrid speciation in
      angiosperm evolution. Here, we show that Yucca gloriosa (Asparagaceae:
      Agavoideae) is the product of intersectional hybridization between Y. aloifolia
      and Y. filamentosa. These species, all named by Carl Linnaeus, exist in sympatry
      along the southeastern Atlantic coast of the United States. Yucca gloriosa was
      found to share a chloroplast haplotype with Y. aloifolia in all populations
      sampled. In contrast, nuclear gene-based microsatellite markers in Y. gloriosa
      are shared with both parents. The hybrid origin of Y. gloriosa is supported by
      multilocus analyses of the nuclear microsatellite markers including principal
      coordinates analysis (PCO), maximum-likelihood hybrid index scoring (HINDEX), and
      Bayesian cluster analysis (STRUCTURE). The putative parental species share only
      one allele at a single locus, suggesting there is little to no introgressive gene
      flow occurring between these species and Y. gloriosa. At the same time,
      diagnostic markers are segregating in Y. gloriosa populations. Lack of variation
      in the chloroplast of Y. aloifolia, the putative maternal parent, makes it
      difficult to rule out multiple hybrid origins of Y. gloriosa, but allelic
      variation at nuclear loci can be explained by a single hybrid origin of Y.
      gloriosa. Overall, these data provide strong support for the homoploid hybrid
      origin of Y. gloriosa.

PMID- 23139881
TI  - Hitchhiking with forests: population genetics of the epiphytic lichen Lobaria
      pulmonaria in primeval and managed forests in southeastern Europe.
AB  - Availability of suitable trees is a primary determinant of range contractions and
      expansions of epiphytic species. However, switches between carrier tree species
      may blur co-phylogeographic patterns. We identified glacial refugia in
      southeastern Europe for the tree-colonizing lichen Lobaria pulmonaria, studied
      the importance of primeval forest reserves for the conservation of genetically
      diverse populations and analyzed differences in spatial genetic structure between
      primeval and managed forests with fungus-specific microsatellite markers.
      Populations belonged to either of two genepools or were admixed. Gene diversity
      was higher in primeval than in managed forests. At small distances up to 170 m,
      genotype diversity was lower in managed compared with primeval forests. We found
      significant associations between groups of tree species and two L. pulmonaria
      genepools, which may indicate "hitchhiking" of L. pulmonaria on forest
      communities during postglacial migration. Genepool B of L. pulmonaria was
      associated with European Beech (Fagus sylvatica) and we can hypothesize that
      genepool B survived the last glaciation associated within the refuge of European
      Beech on the Coastal and Central Dinarides. The allelic richness of genepool A
      was highest in the Alps, which is the evidence for a northern refuge of L.
      pulmonaria. Vicariant altitudinal distributions of the two genepools suggest
      intraspecific ecological differentiation.

PMID- 23139882
TI  - Temperature alters reproductive life history patterns in Batrachochytrium
      dendrobatidis, a lethal pathogen associated with the global loss of amphibians.
AB  - Understanding how pathogens respond to changing environmental conditions is a
      central challenge in disease ecology. The environmentally sensitive fungal
      pathogen Batrachochytrium dendrobatidis (Bd), which causes the amphibian disease
      chytridiomycosis, has spread globally causing amphibian extirpations in a wide
      variety of climatic regions. To gain an in-depth understanding of Bd's responses
      to temperature, we used an integrative approach, combining empirical laboratory
      experiments with mathematical modeling. First, we selected a single Bd isolate
      and serially propagated two lineages of the isolate for multiple generations in
      two stable thermal conditions: 4 degrees C (cold-adapted lineage) and 23 degrees
      C (warm-adapted lineage). We quantified the production of infectious zoospores
      (fecundity), the timing of zoospore release, and zoospore activity in reciprocal
      temperature transplant experiments in which both Bd lineages were grown in either
      high or low temperature conditions. We then developed population growth models
      for the Bd lineages under each set of temperature conditions. We found that Bd
      had lower population growth rates, but longer periods of zoospore activity in the
      low temperature treatment (4 degrees C) compared to the high temperature
      treatment (23 degrees C). This effect was more pronounced in Bd lineages that
      were propagated in the low temperature treatment (4 degrees C), suggesting a
      shift in Bd's response to low temperature conditions. Our results provide novel
      insights into the mechanisms by which Bd can thrive in a wide variety of
      temperature conditions, potentially altering the dynamics of chytridiomycosis and
      thus, the propensity for Bd to cause amphibian population collapse. We also
      suggest that the adaptive responses of Bd to thermal conditions warrant further
      investigation, especially in the face of global climate change.

PMID- 23139883
TI  - Fragmentation reduces regional-scale spatial genetic structure in a wind
      pollinated tree because genetic barriers are removed.
AB  - Gene flow strongly influences the regional genetic structuring of plant
      populations. Seed and pollen dispersal patterns can respond differently to the
      increased isolation resulting from habitat fragmentation, with unpredictable
      consequences for gene flow and population structuring. In a recently fragmented
      landscape we compared the pre- and post-fragmentation genetic structure of
      populations of a tree species where pollen and seed dispersal respond
      differentially to forest fragmentation generated by flooding. Castanopsis
      sclerophylla is wind-pollinated, with seeds that are dispersed by gravity and
      rodents. Using microsatellites, we found no significant difference in genetic
      diversity between pre- and post-fragmentation cohorts. Significant genetic
      structure was observed in pre-fragmentation cohorts, due to an unknown genetic
      barrier that had isolated one small population. Among post-fragmentation cohorts
      this genetic barrier had disappeared and genetic structure was significantly
      weakened. The strengths of genetic structuring were at a similar level in both
      cohorts, suggesting that overall gene flow of C. sclerophylla has been unchanged
      by fragmentation at the regional scale. Fragmentation has blocked seed dispersal
      among habitats, but this appears to have been compensated for by enhanced pollen
      dispersal, as indicated by the disappearance of a genetic barrier, probably as a
      result of increased wind speeds and easier pollen movement over water. Extensive
      pollen flow can counteract some negative effects of fragmentation and assist the
      long-term persistence of small remnant populations.

PMID- 23139884
TI  - Inbreeding and outbreeding depression in Stylidium hispidum: implications for
      mixing seed sources for ecological restoration.
AB  - The benefits of composite rather than local seed provenances for ecological
      restoration have recently been argued, largely on the basis of maximizing
      evolutionary potential. However, these arguments have downplayed the potentially
      negative consequences of outbreeding depression once mixed provenances
      interbreed. In this study, we compared intraspecific F1 hybrid performance and
      molecular marker differentiation among four populations of Stylidium hispidum, a
      species endemic to Southwestern Australia. Multivariate ordination of 134 AFLP
      markers analyzed genetic structure and detected two clusters of paired sites that
      diverged significantly for marker variation along a latitudinal boundary. To test
      for outbreeding depression and to determine the consequences of molecular
      population divergence for hybrid fitness, we conducted controlled pollinations
      and studied germination and survival for three cross categories (within
      population crosses, short- and long-distance F1 hybrids) for paired sites
      distributed within and between the two genetically differentiated regions. We
      found evidence of outbreeding depression in long-distance hybrids (111-124 km),
      and inbreeding depression among progeny of within-population crosses, relative to
      short-distance (3-10 km) hybrids, suggesting an intermediate optimal outcrossing
      distance in this species. These results are discussed in light of the
      evolutionary consequences of mixing seed sources for biodiversity restoration.

PMID- 23139885
TI  - Out of Florida: mtDNA reveals patterns of migration and Pleistocene range
      expansion of the Green Anole lizard (Anolis carolinensis).
AB  - Anolis carolinensis is an emerging model species and the sole member of its genus
      native to the United States. Considerable morphological and physiological
      variation has been described in the species, and the recent sequencing of its
      genome makes it an attractive system for studies of genome variation. To inform
      future studies of molecular and phenotypic variation within A. carolinensis, a
      rigorous account of intraspecific population structure and relatedness is needed.
      Here, we present the most extensive phylogeographic study of this species to
      date. Phylogenetic analyses of mitochondrial DNA sequence data support the
      previous hypothesis of a western Cuban origin of the species. We found five well
      supported, geographically distinct mitochondrial haplotype clades throughout the
      southeastern United States. Most Florida populations fall into one of three
      divergent clades, whereas the vast majority of populations outside Florida belong
      to a single, shallowly diverged clade. Genetic boundaries do not correspond to
      major rivers, but may reflect effects of Pleistocene glaciation events and the
      Appalachian Mountains on migration and expansion of the species. Phylogeographic
      signal should be examined using nuclear loci to complement these findings.

PMID- 23139886
TI  - Choice of hydrogen uptake (Hup) status in legume-rhizobia symbioses.
AB  - The H(2) is an obligate by-product of N-fixation. Recycling of H(2) through
      uptake hydrogenase (Hup) inside the root nodules of leguminous plants is often
      considered an advantage for plants. However, many of the rhizobium-legume
      symbioses found in nature, especially those used in agriculture are shown to be
      Hup(-), with the plants releasing H(2) produced by nitrogenase activity from root
      nodules into the surrounding rhizosphere. Recent studies have suggested that,
      H(2) induces plant-growth-promoting rhizobacteria, which may explain the
      widespread of Hup(-) symbioses in spite of the low energy efficiency of such
      associations. Wild legumes grown in Nova Scotia, Canada, were surveyed to
      determine if any plant-growth characteristics could give an indication of Hup
      choice in leguminous plants. Out of the plants sampled, two legumes, Securigera
      varia and Vicia cracca, showed Hup(+) associations. Securigera varia exhibited
      robust root structure as compared with the other plants surveyed. Data from the
      literature and the results from this study suggested that plants with established
      root systems are more likely to form the energy-efficient Hup(+) symbiotic
      relationships with rhizobia. Conversely, Hup(-) associations could be beneficial
      to leguminous plants due to H(2)-oxidizing plant-growth-promoting rhizobacteria
      that allow plants to compete successfully, early in the growing season. However,
      some nodules from V. cracca tested Hup(+), while others were Hup(-). This was
      similar to that observed in Glycine max and Pisum sativum, giving reason to
      believe that Hup choice might be affected by various internal and environmental
      factors.

PMID- 23139887
TI  - Geographic mosaic of symbiont selectivity in a genus of epiphytic cyanolichens.
AB  - In symbiotic systems, patterns of symbiont diversity and selectivity are crucial
      for the understanding of fundamental ecological processes such as dispersal and
      establishment. The lichen genus Nephroma (Peltigerales, Ascomycota) has a nearly
      cosmopolitan distribution and is thus an attractive model for the study of
      symbiotic interactions over a wide range of spatial scales. In this study, we
      analyze the genetic diversity of Nephroma mycobionts and their associated Nostoc
      photobionts within a global framework. The study is based on Internal Transcribed
      Spacer (ITS) sequences of fungal symbionts and tRNA(L) (eu) (UAA) intron
      sequences of cyanobacterial symbionts. The full data set includes 271 Nephroma
      and 358 Nostoc sequences, with over 150 sequence pairs known to originate from
      the same lichen thalli. Our results show that all bipartite Nephroma species
      associate with one group of Nostoc different from Nostoc typically found in
      tripartite Nephroma species. This conserved association appears to have been
      inherited from the common ancestor of all extant species. While specific
      associations between some symbiont genotypes can be observed over vast distances,
      both symbionts tend to show genetic differentiation over wide geographic scales.
      Most bipartite Nephroma species share their Nostoc symbionts with one or more
      other fungal taxa, and no fungal species associates solely with a single Nostoc
      genotype, supporting the concept of functional lichen guilds. Symbiont
      selectivity patterns within these lichens are best described as a geographic
      mosaic, with higher selectivity locally than globally. This may reflect specific
      habitat preferences of particular symbiont combinations, but also the influence
      of founder effects.

PMID- 23139888
TI  - Variation in resistance to multiple pathogen species: anther smuts of Silene
      uniflora.
AB  - The occurrence of multiple pathogen species on a shared host species is
      unexpected when they exploit the same micro-niche within the host individual. One
      explanation for such observations is the presence of pathogen-specific
      resistances segregating within the host population into sites that are
      differentially occupied by the competing pathogens. This study used experimental
      inoculations to test whether specific resistances may contribute to the
      maintenance of two species of anther-smut fungi, Microbotryum silenes-inflatae
      and Microbotryum lagerheimii, in natural populations of Silene uniflora in
      England and Wales. Overall, resistance to the two pathogens was strongly
      positively correlated among host populations and to a lesser degree among host
      families within populations. A few instances of specific resistance were also
      observed and confirmed by replicated inoculations. The results suggest that
      selection for resistance to one pathogen may protect the host from the emergence
      via host shifts of related pathogen species, and conversely that co-occurrence of
      two species of pathogens may be dependent on the presence of host genotypes
      susceptible to both.

PMID- 23139889
TI  - Unique haplotypes in ant-attended aphids and widespread haplotypes in non
      attended aphids.
AB  - Aphid species within the genus Tuberculatus Mordvilko (Hemiptera: Aphididae)
      exhibit a variety of interactions with ants, ranging from close associations to
      non-attendance. A previous study indicated that despite wing possession, ant
      attended Tuberculatus species exhibited low dispersal rates compared with non
      attended species. This study examined if presence or absence of mutualistic
      interactions and habitat continuity of host plants affected intraspecific genetic
      diversity and genetic differentiation in mitochondrial DNA cytochrome oxidase I
      (COI) sequences. Sympatric ant-attended Tuberculatus quercicola (Matsumura)
      (Hemiptera: Aphididae) and non-attended Tuberculatus paiki Hille Ris Lambers
      (Hemiptera: Aphididae) were collected from the daimyo oak Quercus dentata
      Thunberg (Fagales: Fagaceae) in Japan and examined for haplotype variability.
      Seventeen haplotypes were identified in 568 T. quercicola individuals
      representing 23 populations and seven haplotypes in 425 T. paiki representing 19
      populations. Haplotype diversity, which indicates the mean number of differences
      between all pairs of haplotypes in the sample, and nucleotide diversity were
      higher in T. quercicola than T. paiki. Analysis of molecular variance (AMOVA)
      showed higher genetic differentiation among populations within groups of T.
      quercicola (39.8%) than T. paiki (22.6%). The effects of attendant ant species on
      genetic differentiation in T. quercicola were not distinguishable from geographic
      factors. Despite low dispersal rates, host plant habitat continuity might
      facilitate widespread dispersal of a T. quercicola haplotype in Hokkaido. These
      results suggested that following T. quercicola colonization, gene flow among
      populations was limited, resulting in genetic drift within populations. However,
      frequent T. paiki dispersal is clearly evident by low genetic differentiation
      among populations within groups, resulting in lower haplotype diversity.

PMID- 23139890
TI  - Y-chromosome evidence supports widespread signatures of three-species Canis
      hybridization in eastern North America.
AB  - There has been considerable discussion on the origin of the red wolf and eastern
      wolf and their evolution independent of the gray wolf. We analyzed mitochondrial
      DNA (mtDNA) and a Y-chromosome intron sequence in combination with Y-chromosome
      microsatellites from wolves and coyotes within the range of extensive wolf-coyote
      hybridization, that is, eastern North America. The detection of divergent Y
      chromosome haplotypes in the historic range of the eastern wolf is concordant
      with earlier mtDNA findings, and the absence of these haplotypes in western
      coyotes supports the existence of the North American evolved eastern wolf (Canis
      lycaon). Having haplotypes observed exclusively in eastern North America as a
      result of insufficient sampling in the historic range of the coyote or that these
      lineages subsequently went extinct in western geographies is unlikely given that
      eastern-specific mtDNA and Y-chromosome haplotypes represent lineages divergent
      from those observed in extant western coyotes. By combining Y-chromosome and
      mtDNA distributional patterns, we identified hybrid genomes of eastern wolf,
      coyote, gray wolf, and potentially dog origin in Canis populations of central and
      eastern North America. The natural contemporary eastern Canis populations
      represent an important example of widespread introgression resulting in hybrid
      genomes across the original C. lycaon range that appears to be facilitated by the
      eastern wolf acting as a conduit for hybridization. Applying conventional
      taxonomic nomenclature and species-based conservation initiatives, particularly
      in human-modified landscapes, may be counterproductive to the effective
      management of these hybrids and fails to consider their evolutionary potential.

PMID- 23139891
TI  - Weak patriline effects are present in the cuticular hydrocarbon profiles of
      isolated Formica exsecta ants but they disappear in the colony environment.
AB  - Chemical recognition cues are used to discriminate among species, con-specifics,
      and potentially between patrilines in social insect colonies. There is an ongoing
      debate about the possible persistence of patriline cues despite evidence for the
      mixing of colony odors via a "gestalt" mechanism in social insects, because
      patriline recognition could lead to nepotism. We analyzed the variation in
      recognition cues (cuticular hydrocarbons) with different mating frequencies or
      queen numbers in 688 Formica exsecta ants from 76 colonies. We found no increase
      in the profile variance as genetic diversity increased, indicating that patriline
      effects were absent or possibly obscured by a gestalt mechanism. We then
      demonstrated that an isolated individual's profile changed considerably relative
      to their colony profile, before stabilizing after 5 days. We used these isolated
      individuals to eliminate the masking effects of the gestalt mechanism, and we
      detected a weak but statistically significant patriline effect in isolated adult
      workers and also in newly emerged callow workers. Thus, our evidence suggests
      that genetic variation in the cuticular hydrocarbon profile of F. exsecta ants (n
      alkanes and alkenes) resulted in differences among patrilines, but they were
      obscured in the colony environment, thereby avoiding costly nepotistic behaviors.

PMID- 23139892
TI  - Interactive effects between diet and genotypes of host and pathogen define the
      severity of infection.
AB  - Host resistance and parasite virulence are influenced by multiple interacting
      factors in complex natural communities. Yet, these interactive effects are seldom
      studied concurrently, resulting in poor understanding of host-pathogen
      environment dynamics. Here, we investigated how the level of opportunist pathogen
      virulence, strength of host immunity and the host condition manipulated via diet
      affect the survival of wood tiger moth Parasemia plantaginis (Arctidae). Larvae
      from "low cuticular melanin" and "high cuticular melanin" (considered as low and
      high pathogen resistance, respectively) selection lines were infected with
      moderately and highly virulent bacteria strains of Serratia marcescens, while
      simultaneously manipulating host diet (with or without antibacterial compounds).
      We measured host survival and food preference before and after infection to test
      whether the larvae "self-medicate" by choosing an anti-infection diet (Plantago
      major, i.e., plantain leaf) over lettuce (Lactuca sativa). "High melanin" larvae
      were more resistant than "low melanin" larvae to the less virulent strain that
      had slower growth and colonization rate compared with the more virulent strain.
      Cuticular melanin did not enhance survival when the larvae were infected with the
      highly virulent strain. Anti-infection diet enhanced survival of the "high
      melanin" but not the "low melanin" hosts. Survival was dependent on family origin
      even within the melanin selection lines. Despite the intrinsic preference for
      lettuce, no evidence of self-medication was found. These results demonstrate that
      the relative benefit of host cuticular melanin depends on both diet and pathogen
      virulence: plantain diet only boosted the immunity of already resistant "high
      melanin" hosts, and cuticular melanin increased host survival only when infected
      with moderately virulent pathogen. Moreover, there was considerable variation in
      host survival between families within both melanin lines suggesting genetic basis
      for resistance. These results indicate that although melanin is an important
      predictor of insect immunity, its effect on disease outcomes greatly depends on
      other interacting factors.

PMID- 23139893
TI  - Effective/census population size ratio estimation: a compendium and appraisal.
AB  - With an ecological-evolutionary perspective increasingly applied toward the
      conservation and management of endangered or exploited species, the genetic
      estimation of effective population size (N(e)) has proliferated. Based on a
      comprehensive analysis of empirical literature from the past two decades, we
      asked: (i) how often do studies link N(e) to the adult census population size
      (N)? (ii) To what extent is N(e) correctly linked to N? (iii) How readily is
      uncertainty accounted for in both N(e) and N when quantifying N(e)/N ratios? and
      (iv) how frequently and to what degree might errors in the estimation of N(e) or
      N affect inferences of N(e)/N ratios? We found that only 20% of available N(e)
      estimates (508 of 2617; 233 studies) explicitly attempted to link N(e) and N; of
      these, only 31% (160 of 508) correctly linked N(e) and N. Moreover, only 7% (41
      of 508) of N(e)/N ratios (correctly linked or not) reported confidence intervals
      for both N(e) and N; for those cases where confidence intervals were reported for
      N(e) only, 31% of N(e)/N ratios overlapped with 1, of which more than half also
      reached below N(e)/N = 0.01. Uncertainty in N(e)/N ratios thus sometimes spanned
      at least two orders of magnitude. We conclude that the estimation of N(e)/N
      ratios in natural populations could be significantly improved, discuss several
      options for doing so, and briefly outline some future research directions.

PMID- 23139896
TI  - Next generation sequence analysis and computational genomics using graphical
      pipeline workflows.
AB  - Whole-genome and exome sequencing have already proven to be essential and
      powerful methods to identify genes responsible for simple Mendelian inherited
      disorders. These methods can be applied to complex disorders as well, and have
      been adopted as one of the current mainstream approaches in population genetics.
      These achievements have been made possible by next generation sequencing (NGS)
      technologies, which require substantial bioinformatics resources to analyze the
      dense and complex sequence data. The huge analytical burden of data from genome
      sequencing might be seen as a bottleneck slowing the publication of NGS papers at
      this time, especially in psychiatric genetics. We review the existing methods for
      processing NGS data, to place into context the rationale for the design of a
      computational resource. We describe our method, the Graphical Pipeline for
      Computational Genomics (GPCG), to perform the computational steps required to
      analyze NGS data. The GPCG implements flexible workflows for basic sequence
      alignment, sequence data quality control, single nucleotide polymorphism
      analysis, copy number variant identification, annotation, and visualization of
      results. These workflows cover all the analytical steps required for NGS data,
      from processing the raw reads to variant calling and annotation. The current
      version of the pipeline is freely available at http://pipeline.loni.ucla.edu.
      These applications of NGS analysis may gain clinical utility in the near future
      (e.g., identifying miRNA signatures in diseases) when the bioinformatics approach
      is made feasible. Taken together, the annotation tools and strategies that have
      been developed to retrieve information and test hypotheses about the functional
      role of variants present in the human genome will help to pinpoint the genetic
      risk factors for psychiatric disorders. 

PMID- 23139897
TI  - Gene-Diet Interactions in Complex Disease: Current Findings and Relevance for
      Public Health.
AB  - Rates of obesity and related complex diseases such as type 2 diabetes and
      cardiovascular disease have climbed sharply over the past decades, in parallel
      with shift from principally more active lifestyle and nutritionally dense
      tradition diet to sedentary lifestyle and more energy-dense, Western-pattern
      diet. In the past few years, advances in genotyping technology and in particular
      a number of large-scale genome-wide association studies have made great strides
      in unraveling the genetic basis of complex diseases; and the growing inventory of
      genetic variation is facilitating efforts to investigate gene-diet interactions.
      Understanding gene-diet interaction has the potential to promote diet
      modifications on the basis of genetic makeup. Several recent large-scale studies
      found reproducible evidence showing consumption of sugar sweetened beverages or
      dietary patterns might modulate genetic predisposition to obesity or
      cardiovascular disease. Analyses in randomized trials also showed that genetic
      markers for obesity, diabetes, or cardiovascular disease might modify the
      metabolic response to weight-loss diets. However, little of the knowledge about
      gene-diet interaction has been applied in public health practice; and opinion on
      how genetic testing services are offered and interpreted is still divided. This
      review will summarize recent findings regarding obesogenic diet, genetic
      susceptibility, and gene-diet interactions for obesity and related complex
      disorders and will discuss the potential impact of these findings on public
      health practice.

PMID- 23139898
TI  - Gene expression profiles associated with depression in patients with chronic
      hepatitis C (CH-C).
AB  - The standard treatment for CH-C, pegylated interferon-alpha and ribavirin (PEG
      IFN + RBV), is associated with depression. Recent studies have proposed a new
      role for cytokines in the pathogenesis of depression. We aimed to assess
      differential gene expression related to depression in CH-C patients treated with
      PEG-IFN + RBV. We included 67 CH-C patients being treated with PEG-IFN+RBV. Of
      the entire study cohort, 22% had pre-existing depression, while another 37%
      developed new depression in course of the treatment. Pretreatment blood samples
      were collected into PAXgeneTM RNA tubes, the RNAs extracted from peripheral blood
      mononuclear cells (PBMCs) were used for one step RT-PCR to profile 160 mRNAs.
      Differentially expressed genes were separated into up- and down-regulated genes
      according to presence or absence of depression at baseline (pre-existing
      depression) or following the initiation of treatment (treatment-related
      depression). The mRNA expression profile associated with any depression and with
      treatment-related depression included four and six genes, respectively. Our data
      demonstrate a significant down-regulation of TGF-beta1 and the shift of Th1-Th2
      cytokine balance in the depression associated with IFN-based treatment of HCV
      infection. We propose that TGF-beta1 plays an important role in the imbalance of
      Th1/Th2 in patients with CH-C and depression. With further validation, TGF-beta1
      and other components of Th1/Th2 regulation pathway may provide a future marker
      for CH-C patients predisposed to depression.

PMID- 23139899
TI  - The effects of acute responsive high frequency stimulation of the subiculum on
      the intra-hippocampal kainic acid seizure model in rats.
AB  - The effects of acute responsive high frequency stimulation (HFS) to the subiculum
      on seizures and interictal spikes were investigated in a semi-acute kainic acid
      (KA) induced seizure model in rats. Wistar rats (n = 15) were implanted with an
      electrode-cannula complex in the CA3 area, stimulation and recording electrodes
      in the subiculum and another recording electrode at the contralateral motor
      cortex. Two weeks later rats were injected repeatedly with KA (0.05 MUg/0.1 MUL)
      for 3 days with an interval of 48 h. HFS (125 Hz, 100 MUsec) was delivered to the
      subiculum at a predetermined intensity range (100-500 MUA) in the HFS group (n =
      7) when seizures were visually detected, while no stimulation was delivered in
      the sham control group (n = 8). Various severities of seizures were obtained
      (Stage I-V) and all rats of both groups reached Stage V (Racine's scale) on Day
      1. The HFS group had less focal seizures and a longer inter-focal seizure
      interval on Day 1. Interictal spike rate was also lower in the HFS group and
      decreased with injection days. Significant day effects were found for the
      latency, number of focal seizures, and duration of focal seizures and generalized
      seizures while differences between groups were no longer present. Responsive HFS
      did not disrupt ongoing seizures. However, focal seizures and interictal spikes
      were suppressed by HFS. Such anticonvulsant effects of acute subicular
      stimulation indicate that the subiculum is involved in seizure generation. The
      reduction of seizure sensitivity over the injection day reflects an intrinsic
      anticonvulsant mechanism.

PMID- 23139900
TI  - Characterization of recovered walking patterns and motor control after contusive
      spinal cord injury in rats.
AB  - Currently, complete recovery is unattainable for most individuals with spinal
      cord injury (SCI). Instead, recovery is typically accompanied by persistent
      sensory and motor deficits. Restoration of preinjury function will likely depend
      on improving plasticity and integration of these impaired systems. Eccentric
      muscle actions require precise integration of sensorimotor signals and are
      predominant during the yield (E2) phase of locomotion. Motor neuron activation
      and control during eccentric contractions is impaired across a number of central
      nervous system (CNS) disorders, but remains unexamined after SCI. Therefore, we
      characterized locomotor recovery after contusive SCI using hindlimb (HL)
      kinematics and electromyographic (EMG) recordings with specific consideration of
      eccentric phases of treadmill (TM) walking. Deficits in E2 and a caudal shift of
      locomotor subphases persisted throughout the 3-week recovery period. EMG records
      showed notable deficits in the semitendinosus (ST) during yield. Unlike other HL
      muscles, recruitment of ST changed with recovery. At 7 days, the typical dual
      burst pattern of ST was lost and the second burst (ST2) was indistinct. By 21
      days, the dual-burst pattern returned, but latencies remained impaired. We show
      that ST2 burst duration is highly predictive of open field Basso, Beattie,
      Bresnahan (BBB) scores. Moreover, we found that simple changes in locomotor
      specificity which enhance eccentric actions result in new motor patterns after
      SCI. Our findings identify a caudal shift in stepping kinematics, irregularities
      in E2, and aberrant ST2 bursting as markers of incomplete recovery. These
      residual impairments may provide opportunities for targeted rehabilitation.

PMID- 23139901
TI  - The association between cingulate cortex glutamate concentration and delay
      discounting is mediated by resting state functional connectivity.
AB  - Humans vary in their ability to delay gratification and impulsive decision making
      is a common feature in various psychiatric disorders. The level of delay
      discounting is a relatively stable psychological trait, and therefore neural
      processes implicated in delay discounting are likely to be based on the overall
      functional organization of the brain (under task-free conditions) in which state
      dependent shifts from baseline levels occur. The current study investigated
      whether delay discounting can be predicted by intrinsic properties of brain
      functioning. Fourteen healthy male subjects performed a delay discounting task.
      In addition, resting state functional magnetic resonance imaging (fMRI) and
      magnetic resonance spectroscopy (1H MRS) were used to investigate the
      relationship between individual differences in delay discounting and molecular
      and regional measures of resting state (baseline) activity of dorsal anterior
      cingulate cortex (dACC). Results showed that delay discounting was associated
      with both dACC glutamate concentrations and resting state functional connectivity
      of the dACC with a midbrain region including ventral tegmental area and
      substantia nigra. In addition, a neural pathway was established, showing that the
      effect of glutamate concentrations in the dACC on delay discounting is mediated
      by functional connectivity of the dACC with the midbrain. The current findings
      are important to acknowledge because spontaneous intrinsic brain processes have
      been proposed to be a potential promising biomarker of disease and impulsive
      decision making is associated with several psychiatric disorders.

PMID- 23139902
TI  - Deletion of galectin-3 exacerbates microglial activation and accelerates disease
      progression and demise in a SOD1(G93A) mouse model of amyotrophic lateral
      sclerosis.
AB  - Galectins are pleiotropic carbohydrate-binding lectins involved in inflammation,
      growth/differentiation, and tissue remodeling. The functional role of galectins
      in amyotrophic lateral sclerosis (ALS) is unknown. Expression studies revealed
      increases in galectin-1 mRNA and protein in spinal cords from SOD1(G93A) mice,
      and in galectin-3 and -9 mRNAs and proteins in spinal cords of both SOD1(G93A)
      mice and sporadic ALS patients. As the increase in galectin-3 appeared in early
      presymptomatic stages and increased progressively through to end stage of disease
      in the mouse, it was selected for additional study, where it was found to be
      mainly expressed by microglia. Galectin-3 antagonists are not selective and do
      not readily cross the blood-brain barrier; therefore, we generated SOD1(G93A)/Gal
      3(-/-) transgenic mice to evaluate galectin-3 deletion in a widely used mouse
      model of ALS. Disease progression, neurological symptoms, survival, and
      inflammation were assessed to determine the effect of galectin-3 deletion on the
      SOD1(G93A) disease phenotype. Galectin-3 deletion did not change disease onset,
      but resulted in more rapid progression through functionally defined disease
      stages, more severely impaired neurological symptoms at all stages of disease,
      and expiration, on average, 25 days earlier than SOD1(G93A)/Gal-3(+/+) cohorts.
      In addition, microglial staining, as well as TNF-alpha, and oxidative injury were
      increased in SOD1(G93A)/Gal-3(-/-) mice compared with SOD1(G93A)/Gal-3(+/+)
      cohorts. These data support an important functional role for microglial galectin
      3 in neuroinflammation during chronic neurodegenerative disease. We suggest that
      elevations in galectin-3 by microglia as disease progresses may represent a
      protective, anti-inflammatory innate immune response to chronic motor neuron
      degeneration.

PMID- 23139903
TI  - Sensitivity, specificity, and predictive power of the "Brief Risk-resilience
      Index for SCreening," a brief pan-diagnostic web screen for emotional health.
AB  - Few standardized tools are available for time-efficient screening of emotional
      health status across diagnostic categories, especially in primary care. We
      evaluated the 45-question Brief Risk-resilience Index for SCreening (BRISC) and
      the 15-question mini-BRISC in identifying poor emotional health and coping
      capacity across a range of diagnostic groups - compared with a detailed clinical
      assessment - in a large sample of adult outpatients. Participants 18-60 years of
      age (n = 1079) recruited from 12 medical research and clinical sites completed
      the computerized assessments. Three index scores were derived from the full BRISC
      and the mini-BRISC: one for risk (negativity-positivity bias) and two for coping
      (resilience and social capacity). Summed answers were converted to standardized z
      scores. BRISC scores were compared with detailed health assessment and diagnostic
      interview (for current psychiatric, psychological, and neurological conditions)
      by clinicians at each site according to diagnostic criteria. Clinicians were
      blinded to BRISC scores. Clinical assessment stratified participants as having
      "clinical" (n = 435) or "healthy" (n = 644) diagnostic status. Receiver operating
      characteristic analyses showed that a z-score threshold of -1.57 on the full
      BRISC index of emotional health provided an optimal classification of "clinical"
      versus "healthy" status (sensitivity: 81.2%, specificity: 92.7%, positive
      predictive power: 80.2%, and negative predictive power: 93.1%). Comparable
      findings were revealed for the mini-BRISC. Negativity-positivity bias index
      scores contributed the most to prediction. The negativity-positivity index of
      emotional health was most sensitive to classifying major depressive disorder
      (100%), posttraumatic stress disorder (95.8%), and panic disorder (88.7%). The
      BRISC and mini-BRISC both offer a brief, clinically useful screen to identify
      individuals at risk of disorders characterized by poor emotion regulation, from
      those with good emotional health and coping.

PMID- 23139904
TI  - Maximum carotid artery wall thickness and risk factors in a young primary
      prevention population.
AB  - Maximum carotid artery wall thickness was utilized in a primary prevention
      population and compared with baseline risk factors. Carotid wall thickness was
      measured between the blood-intima and media-adventitia interfaces by B-mode
      ultrasonography using software calipers at points of protrusion. Long-axis
      measures were confirmed by short-axis assessment. The maximum carotid wall
      thickness for each subject was divided by age in years to yield an annual
      accretion rate (called carotid intima-media thickness accretion rate [CIMTAR]).
      The entire study population was then divided by median CIMTAR to investigate the
      association with baseline variables used in standard risk assessments with the
      bifurcated groups. Traditional risk factors such as age, diabetes, smoking,
      hyperlipidemia, and obesity were not associated with greater than median CIMTAR.
      Only male gender (P = 0.02) and systolic blood pressure (P = 0.002) in baseline
      variables were associated with an elevated CIMTAR for the entire population.
      Among those not taking lipid-lowering therapy at baseline, only systolic blood
      pressure remained significant (P = 0.0002). Correlations between low-density
      lipoprotein (LDL) cholesterol level and maximum carotid wall thickness/CIMTAR
      were weak for the entire population (r = -0.17/r = -0.12, respectively). Measure
      of maximum carotid wall thickness may select patients earlier for treatment than
      traditional risk factors. The addition of CIMTAR to risk algorithms may permit a
      single-point assignation of subsequent vascular risk that is more efficacious
      than traditional risk factors.

PMID- 23139905
TI  - Role of C-terminal negative charges and tyrosine residues in fibril formation of
      alpha-synuclein.
AB  - alpha-Synuclein (140 amino acids), one of the causative proteins of Parkinson's
      disease, forms amyloid fibrils in brain neuronal cells. In order to further
      explore the contributions of the C-terminal region of alpha-synuclein in fibril
      formation and also to understand the overall mechanism of fibril formation, we
      reduced the number of negatively charged residues in the C-terminal region using
      mutagenesis. Mutants with negative charges deleted displayed accelerated fibril
      formation compared with wild-type alpha-synuclein, demonstrating that negative
      charges located in the C-terminal region of alpha-synuclein modulate fibril
      formation. Additionally, when tyrosine residues located at position 125, 133, and
      136 in the C-terminal region were changed to alanine residue(s), we found that
      all mutants containing the Tyr136Ala mutation showed delays in fibril formation
      compared with wild type. Mutation of Tyr136 to various amino acids revealed that
      aromatic residues located at this position act favorably toward fibril formation.
      In mutants where charge neutralization and tyrosine substitution were combined,
      we found that these two factors influence fibril formation in complex fashion.
      These findings highlight the importance of negative charges and aromatic side
      chains in the C-terminal region of alpha-synuclein in fibril formation.

PMID- 23139906
TI  - Altered integration of speech and gesture in children with autism spectrum
      disorders.
AB  - The presence of gesture during speech has been shown to impact perception,
      comprehension, learning, and memory in normal adults and typically developing
      children. In neurotypical individuals, the impact of viewing co-speech gestures
      representing an object and/or action (i.e., iconic gesture) or speech rhythm
      (i.e., beat gesture) has also been observed at the neural level. Yet, despite
      growing evidence of delayed gesture development in children with autism spectrum
      disorders (ASD), few studies have examined how the brain processes multimodal
      communicative cues occurring during everyday communication in individuals with
      ASD. Here, we used a previously validated functional magnetic resonance imaging
      (fMRI) paradigm to examine the neural processing of co-speech beat gesture in
      children with ASD and matched controls. Consistent with prior observations in
      adults, typically developing children showed increased responses in right
      superior temporal gyrus and sulcus while listening to speech accompanied by beat
      gesture. Children with ASD, however, exhibited no significant modulatory effects
      in secondary auditory cortices for the presence of co-speech beat gesture.
      Rather, relative to their typically developing counterparts, children with ASD
      showed significantly greater activity in visual cortex while listening to speech
      accompanied by beat gesture. Importantly, the severity of their socio
      communicative impairments correlated with activity in this region, such that the
      more impaired children demonstrated the greatest activity in visual areas while
      viewing co-speech beat gesture. These findings suggest that although the
      typically developing brain recognizes beat gesture as communicative and
      successfully integrates it with co-occurring speech, information from multiple
      sensory modalities is not effectively integrated during social communication in
      the autistic brain.

PMID- 23139907
TI  - Mild cognitive impairment: effect of education on the verbal and nonverbal tasks
      performance decline.
AB  - We sought to longitudinally evaluate the potential association of educational
      level with performance on verbal and nonverbal tasks in individuals with mild
      cognitive impairment (MCI). We evaluated patients with MCI, age >50 years, no
      medication intake, absent vascular risk factors, and no lesions on brain magnetic
      resonance imaging (MRI). Each patient underwent a clinical assessment packet and
      a series of neuropsychological tests of the language and constructional praxis
      subtests of Cambridge Cognitive Examination (CAMGOG) and the Boston naming test
      (BNT), at baseline, 6 months, and 12 months. Educational levels were defined
      taking into account the total years of education, the school level, and diplomas.
      MCI patients with low education level showed a stepwise reduction in scores of
      naming objects (NO; P = 0.009), definition (DF; P = 0.012), language (LT; P =
      0.021), constructional praxis (CD; P = 0.022), confrontation naming skills (BXB;
      P = 0.033), phonemic help (BFB; P = 0.041), and BNT (P = 0.002). Analysis of
      covariance, controlling for baseline scores, showed that education was associated
      with NO score (P = 0.002), DF score (P = 0.005), LT (P = 0.008), CD score (P =
      0.008), BXB score (44.36 +/- 1.84, P = 0.0001), BFB (P = 0.022), and BNT (P =
      0.004). Our findings indicate that education appeared to affect verbal and
      nonverbal task performance in MCI patients. Despite the fact that higher educated
      patients are more acquainted with the tasks, slower deterioration in consecutive
      follow-up examinations could be explained by the cognitive reserve theory. The
      potential association of this protective effect with delayed onset of symptoms
      deserves further investigation.

PMID- 23139908
TI  - The expression of nicotinic receptor alpha7 during cochlear development.
AB  - Nicotinic acetylcholine receptor alpha7 expression was examined in the developing
      and adult auditory system using mice that were modified through homologous
      recombination to coexpress either GFP (alpha7GFP) or Cre (alpha7Cre),
      respectively. The expression of alpha7GFP is first detected at embryonic (E) day
      E13.5 in cells of the spiral prominence. By E14.5, sensory regions including the
      putative outer hair cells and Deiters' cells express alpha7GFP as do solitary
      efferent fibers. This pattern diminishes after E16.5 in a basal to apex
      progression, as Hensen's cells and cells of the spiral ligament acquire alpha7GFP
      expression. At birth and thereafter alpha7GFP also identifies a subset of spiral
      ganglion cells whose processes terminate on inner hair cells. Efferent fibers
      identified by peripherin or calcitonin gene-related protein do not coexpress
      alpha7GFP. In addition to cochlear structures, there is strong expression of
      alpha7GFP by cells of the central auditory pathways including the ventral
      posterior cochlear nucleus, lateral lemniscus, central inferior colliculus, and
      the medial geniculate nucleus. Our findings suggest that alpha7 expression by
      both neuronal and non-neuronal cells has the potential to impact multiple
      auditory functions through mechanisms that are not traditionally attributed to
      this receptor.

PMID- 23139909
TI  - Alteration of synergistic muscle activity following neuromuscular electrical
      stimulation of one muscle.
AB  - The aim of the study was to determine muscle activation of the m. triceps surae
      during maximal voluntary contractions (MVCs) following neuromuscular electrical
      stimulation (NMES) of the m. gastrocnemius lateralis (GL). The participants (n =
      10) performed three MVC during pretest, posttest, and recovery, respectively.
      Subsequent to the pretest, the GL was stimulated by NMES. During MVC, force and
      surface electromyography (EMG) of the GL, m. gastrocnemius medialis (GM), and m.
      soleus (SOL) were measured. NMES of GL induced no significant decline (3%) in
      force. EMG activity of the GL decreased significantly to 81% (P < 0.05), whereas
      EMG activity of the synergistic SOL increased to 112% (P < 0.01). The GM (103%, P
      = 1.00) remained unaltered. Decreased EMG activity in the GL was most likely
      caused by failure of the electrical propagation at its muscle fiber membrane. The
      decline of EMG activity in GL was compensated by increased EMG activity of SOL
      during MVC. It is suggested that these compensatory effects are caused by central
      contributions induced by NMES.

PMID- 23139910
TI  - Functional deficits of the attentional networks in autism.
AB  - Attentional dysfunction is among the most consistent observations of autism
      spectrum disorders (ASD). However, the neural nature of this deficit in ASD is
      still unclear. In this study, we aimed to identify the neurobehavioral correlates
      of attentional dysfunction in ASD. We used the Attention Network Test-Revised and
      functional magnetic resonance imaging to examine alerting, orienting, and
      executive control functions, as well as the neural substrates underlying these
      attentional functions in unmedicated, high-functioning adults with ASD (n = 12)
      and matched healthy controls (HC, n = 12). Compared with HC, individuals with ASD
      showed increased error rates in alerting and executive control, accompanied by
      lower activity in the mid-frontal gyrus and the caudate nucleus for alerting, and
      by the absence of significant functional activation in the anterior cingulate
      cortex (ACC) for executive control. In addition, greater behavioral deficiency in
      executive control in ASD was correlated with less functional activation of the
      ACC. These findings of behavioral and neural abnormalities in alerting and
      executive control of attention in ASD may suggest core attentional deficits,
      which require further investigation.

PMID- 23139911
TI  - Prescription stimulants in individuals with and without attention deficit
      hyperactivity disorder: misuse, cognitive impact, and adverse effects.
AB  - Prescription stimulants are often used to treat attention deficit hyperactivity
      disorder (ADHD). Drugs like methylphenidate (Ritalin, Concerta),
      dextroamphetamine (Dexedrine), and dextroamphetamine-amphetamine (Adderall) help
      people with ADHD feel more focused. However, misuse of stimulants by ADHD and
      nonaffected individuals has dramatically increased over recent years based on
      students' misconceptions or simple lack of knowledge of associated risks. In this
      review, we discuss recent advances in the use and increasing misuse of
      prescription stimulants among high school and college students and athletes.
      Given the widespread belief that stimulants enhance performance, there are in
      fact only a few studies reporting the cognitive enhancing effects of stimulants
      in ADHD and nonaffected individuals. Student athletes should be apprised of the
      very serious consequences that can emerge when stimulants are used to improve
      sports performance. Moreover, misuse of stimulants is associated with dangers
      including psychosis, myocardial infarction, cardiomyopathy, and even sudden
      death. As ADHD medications are prescribed for long-term treatment, there is a
      need for long-term safety studies and education on the health risks associated
      with misuse is imperative.

PMID- 23139912
TI  - Behavioral testing in rodent models of orofacial neuropathic and inflammatory
      pain.
AB  - Orofacial pain conditions are often very debilitating to the patient and
      difficult to treat. While clinical interest is high, the proportion of studies
      performed in the orofacial region in laboratory animals is relatively low,
      compared with other body regions. This is partly due to difficulties in testing
      freely moving animals and therefore lack of reliable testing methods. Here we
      present a comprehensive review of the currently used rodent models of
      inflammatory and neuropathic pain adapted to the orofacial areas, taking into
      account the difficulties and drawbacks of the existing approaches. We examine the
      available testing methods and procedures used for assessing the behavioral
      responses in the face in both mice and rats and provide a summary of some
      pharmacological agents used in these paradigms to date. The use of these agents
      in animal models is also compared with outcomes observed in the clinic.

PMID- 23139913
TI  - Stratification substantially reduces behavioral variability in the hypoxic
      ischemic stroke model.
AB  - Stroke is the most common cause of long-term disability, and there are no known
      drug therapies to improve recovery after stroke. To understand how successful
      recovery occurs, dissect candidate molecular pathways, and test new therapies,
      there is a need for multiple distinct mouse stroke models, in which the
      parameters of recovery after stroke are well defined. Hypoxic-ischemic stroke is
      a well-established stroke model, but behavioral recovery in this model is not
      well described. We therefore examined a panel of behavioral tests to see whether
      they could be used to quantify functional recovery after hypoxic-ischemic stroke.
      We found that in C57BL/6J mice this stroke model produces high mortality
      (approximately one-third) and variable stroke sizes, but is fast and easy to
      perform on a large number of mice. Horizontal ladder test performance on day 1
      after stroke was highly and reproducibly correlated with stroke size (P < 0.0001,
      R(2) = 0.7652), and allowed for functional stratification of mice into a group
      with >18% foot faults and 2.1-fold larger strokes. This group exhibited
      significant functional deficits for as long as 3 weeks on the horizontal ladder
      test and through the last day of testing on automated gait analysis (33 days),
      rotarod (30 days), and elevated body swing test (EBST) (36 days). No deficits
      were observed in an automated activity chamber. We conclude that stratification
      by horizontal ladder test performance on day 1 identifies a subset of mice in
      which functional recovery from hypoxic-ischemic stroke can be studied.

PMID- 23139915
TI  - Second hand smoke and cardiovascular disease in Low and Middle Income Countries:
      a case for action.
AB  - Second hand tobacco smoke (SHS) is an environmental toxin and an established
      cause of cardiovascular disease in nonsmokers. Smoke free laws reduce SHS and its
      downstream cardiovascular disease, but until recently evidence to support smoke
      free law implementation in low and middle income country settings was limited. In
      14 low and middle income nations surveyed by the Global Adult Tobacco Survey
      active smoking prevalence in adults (>=15 years old) was universally higher in
      males (range 21.6-60.2%) compared with females (0.5-24.4%), and the highest
      burden of SHS exposure was in women (strong positive association between
      male/female active smoking ratio and female SHS exposure prevalence). A
      systematic review was conducted of MEDLINE-indexed studies of self-reported SHS
      exposure and cardiovascular harms in low or middle income nations. Eight papers
      reported the association of SHS with ischemic heart disease and four reported the
      association of SHS with stroke. For all the studies, and almost all sources of
      SHS surveyed, a strong positive association between SHS and ischemic heart
      disease (main relative odds ratio range 1.17-2.36) and SHS and stroke (odds ratio
      or hazard ratio 1.41-1.49). Prevalence of SHS exposure is high in low and middle
      income nations, especially among women. Epidemiologic evidence supports the
      conclusion that SHS harms are the same across low, middle and high income
      nations. Governments have an obligation to protect citizens from SHS exposure,
      enforcing smoke-free legislation and providing public education about SHS harms.

PMID- 23139916
TI  - OBSTRUCTIVE LUNG DISEASE AND EXPOSURE TO BURNING BIOMASS FUEL IN THE INDOOR
      ENVIRONMENT.
AB  - It is estimated that up to half of the world's population burns biomass fuel
      (wood, crop residues, animal dung and coal) for indoor uses such as cooking,
      lighting and heating. As a result, a large proportion of women and children are
      exposed to high levels of household air pollution (HAP). The short and long term
      effects of these exposures on the respiratory health of this population are not
      clearly understood. On May 9-11, 2011 NIH held an international workshop on the
      "Health Burden of Indoor Air Pollution on Women and Children," in Arlington, VA.
      To gather information on the knowledge base on this topic and identify research
      gaps, ahead of the meeting we conducted a literature search using PubMed to
      identify publications that related to HAP, asthma, and chronic obstructive
      pulmonary disease (COPD). Abstracts were all analyzed and we report on those
      considered by the respiratory sub study group at the meeting to be most relevant
      to the field. Many of the studies published are symptom-based studies (as opposed
      to objective measures of lung function or clinical examination etc.) and
      measurement of HAP was not done. Many found some association between indoor
      exposures to biomass smoke as assessed by stove type (e.g., open fire vs. liquid
      propane gas) and respiratory symptoms such as wheeze and cough. Among the studies
      that examined objective measures (e.g. spirometry) as a health outcome, the data
      supporting an association between biomass smoke exposure and COPD in adult women
      are fairly robust, but the findings for asthma are mixed. If an association was
      observed between the exposures and lung function, most data seemed to demonstrate
      mild to moderate reductions in lung function, the pathophysiological mechanisms
      of which need to be investigated. In the end, the group identified a series of
      scientific gaps and opportunities for research that need to be addressed to
      better understand the respiratory effects of exposure to indoor burning of the
      different forms of biomass fuels.

PMID- 23139917
TI  - [Psychometric properties of the Barratt Impulsiveness Scale in a sample of the
      city of Buenos Aires].
AB  - The Barratt Impulsiveness Scale was designed to assess the impulsivity construct
      in three dimensions: attentional, motor and unplanned. The scale has been applied
      to patients with different diagnoses in which the impulsivity symptoms are
      characteristic. In Argentina there aren't studies that evaluate the psychometrics
      properties of the scale in clinical population. The objective of the research was
      to evaluate the psychometrics properties in a sample of the city of Buenos Aires.
      150 adult subjects were selected: 67 didn't have relevant psychiatric diagnoses,
      56 met criteria for bipolar disorder and 27 had Attention Deficit Disorder. The
      internal consistency, the construct validity, discriminative validity and the
      factorial structure were assessed. The Cronbach alpha was 0.84 for the total
      scale. Also the instrument has demonstrated acceptable indicators of construct
      and discriminative validity. Significant differences were found when the results
      of the present study and the original factorial structure were compared. The
      results support the usefulness of the scale in the psychiatric, scientific and
      clinical context to evaluate the impulsivity construct. The total score of the
      scale obtained the strongest indicators of reliability and validity.

PMID- 23139918
TI  - [Depressive symptoms in primary caregivers of patients diagnosed with paranoid
      schizophrenia attending at a psychiatric office of a general hospital in Lima,
      Peru].
AB  - OBJECTIVE: To determine the prevalence of depressive symptoms in caregivers of
      patients attending at a psychiatric office of a general hospital with diagnosis
      of paranoid schizophrenia and to estimate the correlation between the severity of
      schizophrenia and depressive symptoms in the primary caregiver. METHODS: The Zung
      Depression Scale (ZDS) and the Depressive Psychopathology Scale (DPS) were
      administered to caregivers and the severity of schizophrenia was assessed using
      the scale of Clinical Global Impression (CGI). RESULTS: We evaluated 61 patient
      caregiver pairs. Between the patients; 63.9% were male and 88.5% were single. Of
      the caregivers; 77.05% were women, 47.5% married, and 42.6% were the mothers of
      the patients. The prevalence of probable clinic depression was 3.3% and 14.8%
      according to the DPS (= 25.5) and the ZDS (= 56.25). It was find correlation
      between the caregiver score in the ZDS and the CGI of the patient (rho = 0.317, p
      = 0.0013). The female caregivers had higher scores in ZDS than male caregivers
      (49.65 +/- 8.9 vs. 42.59 +/- 7.15, p = 0.009). CONCLUSIONS: Patients were mostly
      male and single; most caregivers were married, women and mothers of patients.
      Depressive symptoms (according ZDS) in caregivers were higher in female and were
      correlated with the severity of the patient's illness.

PMID- 23139919
TI  - [Pharmacoepidemiological study of the use of psychotropics in hospitalized
      patients].
AB  - OBJECTIVE: To assess consumption and the exposition of patients admitted to the
      Universitary Hospital of the Interamerican Open University (UAI), between October
      and December of 2007-2009. METHODS: Descriptive observational study. The
      information was obtained of the Pharmacia Sector. We analyze the dispensations
      (Units); the exposition was evaluated using the defined daily dose per 100
      beds/day. We analyzed how many of the psychotropics used were considerated
      essentials drugs for the WHO. We assessed the adverse drug reactions registered.
      RESULTS: The psychopharmacological drugs represented the 43%, 41%, and the 44%
      (period 2007-2009) of the drugs used for the Central Nervous System. The
      benzodiazepines represented more of the 50% of the psychopharmacological drugs
      used. The exposure was respectively of 57%, 66%, and 40% (for all the patients
      admitted to the hospital on period 2007-2009). The essential medicines used
      fluctuate between 41% and 48%. From 32 adverse reactions connected with the
      Central Nervous System, 20 (62.5%) were attributed to psychotropics. CONCLUSIONS:
      1. We established the quantity of the psychotropics dispensations, as well as the
      level of the exposure. 2. The psychotropic utilization of the essentials
      medicines list of the WHO was above 40%.

PMID- 23139920
TI  - [Day Hospital: history and conceptualization].
AB  - The appearance of Day Hospitals operated as a model to inspire the different ways
      of partial time psychiatric care (night hospitals, weekend hospitals, long hour
      activities in hospitalization services or general hospitals, etc.) and came to
      complement or replace complete hospitalization in classic psychiatric hospitals.
      This article presents the history and origins of Day Hospitals and their initial
      propagation in different countries, and especially in Argentina. Social and
      political conditions that set their emergence as a therapeutic resource in
      psychiatry, their models of functioning and variants of application according to
      the diagnoses of patients admitted, age groups, etc., the theories put into play
      to report their effects, several studies and technical results, and ideological
      views related to mental disorders and their treatment in the society are also
      being studied.

PMID- 23139921
TI  - [A recovery oriented research approach to a Day Hospital program].
AB  - We are at a turning point for psychiatric practice brought on by the
      consolidation of the recovery paradigm. Both mental health interventions and
      research will have to adapt in order to promote recovery. Interventions will tend
      to focus in the community, and day hospital programs will have to be more
      versatile and also community oriented. The appropriate research approach for
      recovery oriented interventions has to combine quantitative and qualitative
      methods, in order to complementarily inform any given subject. Current hierarchy
      proposed by the evidence based medicine model will have to comply with recovery
      oriented practices, including and adequately appraising qualitative approaches
      and mixed methods. The results of a mixed methods approach to a day hospital
      program is presented, which includes assessment of: clinical state,
      functionality, quality of life, family burden, types of interventions, users and
      carers perspectives.

PMID- 23139922
TI  - [When you see the light of day at the hospital].
AB  - Day Hospital delivers complex treatments to patients with psychiatric illness
      such as psychosis and severe neurosis. Interdisciplinary work is necessarily
      required by this device. Our Day Hospital is organized in three sections:
      community area, clinical area and education and research. Our practice isn't
      exempt of hindrances, which relate not only to the clinical specifics we deal
      with, but also with the social, cultural and legal contexts it develops in. Since
      the approval of the Mental Health National Law (no. 26657) we believe the Day
      Hospital, our old resource, is given the opportunity to keep fulfilling a space
      as a proposal both fresh and institutional. The mentioned law states that Day
      Hospitals are to be promoted as a means for social, labor and community inclusion
      of patients. We have no doubt on the legal advance this represents but, on daily
      practice, issues will persist until a strong change decision is shown,
      implemented as public health policies aligned with the law.

PMID- 23139923
TI  - [Challenges and present situation in private practice in psychiatric Day Hospital
      and other intermediate devices].
AB  - The daily clinical practice in Psychiatric Day Hospitals has experimented several
      changes in the last recent years. These changes are the result of numerous
      situations: new laws, extensions and reductions in therapeutic covering from pre
      paid medical services, social security, new follow up programs for outpatients,
      more access to disability certificates, better possibilities to provide free-cost
      medications to chronic ill patients. However, on the other hand, the
      popularization of clinic works, statistics, and -over all- training of
      professionals is still scarcely frequent, so that its inclusion could be
      considered as part of the many therapeutic alternatives for severe ill patients.

PMID- 23139924
TI  - [The Day Hospital: being oriented by the symptom].
AB  - The contribution of psychoanalysis to the clinic psychosis is studied in the
      context of a Day Hospital located in a Health Mental Service of a General
      Hospital of Buenos Aires City. The specificity of this practice is covered from
      the psychoanalytic conception of the symptom. Three cases are presented that
      allows realizing the different uses of the device.

PMID- 23139925
TI  - [Claudins as prognostic factors of breast cancer].
AB  - Different expression of claudins and E-cadherin has been described in the
      pathogenesis and progression of breast cancer. Changes in the expression of these
      junctional molecules have also been described as being of prominent importance in
      other cancers as well. Thus, we aimed at exploring the potential prognostic
      relevance of these cell junctional molecules in breast carcinoma cases.
      Expression of claudin-1, -3, -4, -5, -7, -8, -10, -15, -18 and E-cadherin at mRNA
      level was evaluated in correlation with survival in publicly available datasets
      containing expression measurements of 1809 breast cancer patients. Breast cancer
      tissues of 636 patients were evaluated with tissue microarray technique and
      immunohistochemical method for claudin-1, -2, -3, -4, -5, -7 and E-cadherin
      protein expression. In 96 cases lymph node metastases were also subjects of the
      study. Claudin expression bears prognostic information in itself. Based on
      bioinformatic data analysis, the meta-gene of claudin-3, -4, -7 and E-cadherin
      has proved the most powerful in predicting survival. An immunohistochemical
      protein profile consisting of claudin-2, -4 and E-cadherin was able to predict
      outcome in the most effective manner in the training set. Combining the
      overlapping members of the distinct methods resulted in the CC index (consisting
      of claudin-4 and E-cadherin, a.k.a. CURIO), which was able to accurately predict
      relapse-free survival in the validation cohort (p=0.029) in a more efficient way
      than its components. Cox regression analysis including clinicopathological
      variables and the average CC score showed that in univariate analysis most of
      them were prognostic but most of them lost independent prognostic value in
      multivariate analysis except for the CC index, the subtypes defined by
      immunoprofiling and vascular invasion. On the other hand, the CC index was able
      to further refine prognosis splitting good vs. poor prognosis patients into two
      clusters in these subgroups. Evaluation of lymph node metastases has shown that
      decreased expression of claudin-1 and elevated expression of claudin-4 can
      predict worse prognosis in breast cancers spreading to the regional lymph nodes.
      The defined claudin-cadherin index provides additional prognostic information
      besides the routinely utilized diagnostic approaches and factors. The level of
      expression of certain claudins can be of prognostic significance in regional
      lymph node metastases.

PMID- 23139926
TI  - A simple method for the determination of enantiomeric composition of propranolol
      enantiomers.
AB  - A simple method of room temperature phosphorescence is proposed for the
      determination of propranolol enantiomeric composition based on beta-cyclodextrin
      as the chiral host and bromocyclohexane as the heavy atom. Enantiomeric complexes
      are formed upon binding of the propranolol enantiomer to beta-cyclodextrin, and
      the sign of the resultant phosphorescence signals allows for the identity of the
      propranolol enantiomers configuration to be determined successfully.

PMID- 23139927
TI  - Fine-tuning the specificity of boronate affinity monoliths toward glycoproteins
      through pH manipulation.
AB  - Boronate affinity functionalized materials have recently drawn increasing
      attention due to their capability to selectively isolate and enrich glycoproteins
      and glycopeptides. As cheaper and more stable competitors to lectins, boronic
      acids are generally believed to yield a relatively wider spectrum specificity to
      glycoproteins. For better understanding and effective utilization of boronate
      affinity, it is necessary to establish if boronic acids exhibit lectin-like
      narrow specificity towards individual or a sub-class of glycoproteins. Here we
      report a pH manipulation strategy for fine-tuning the specificity of boronate
      affinity monoliths towards two sub-classes of glycoproteins, sialylated and
      nonsialylated glycoproteins. When the binding pH > the pK(a) of the boronic acid
      by one pH unit or more, the boronate affinity monolith preferentially binds to
      glycoproteins containing neutral sugars and excludes sialic acid containing
      glycoproteins due to electrostatic repulsion. When the binding pH < the pK(a) by
      one pH unit or more, the boronate affinity monolith binds to sialylated
      glycoproteins due to the exceptional binding affinity of the boronic acid towards
      sialic acid residues. The alternative specificity towards sialic acid and neutral
      sugar was first verified using an off-line combination of boronate affinity
      extraction with nano-ESI-Orbitrap MS/MS detection. The alternative specificity
      towards sialylated and nonsialylated glycoproteins was then demonstrated by means
      of off-line combination of boronate affinity extraction with MALDI-TOF MS.
      Finally, the developed approach was applied to the alternative extraction of
      intact sialylated and nonsialylated glycoproteins spiked in human serum.

PMID- 23139928
TI  - Fast and continuous-flow separation of DNA-complexes and topological DNA variants
      in microfluidic chip format.
AB  - The efficient detection, separation and purification of topological and (protein
      )complexed DNA variants is mandatory for many state-of-the-art molecular medicine
      technologies, like medical diagnostics, gene- and cancer-therapy as well as
      plasmid vaccination. Here, we present the proof-of-concept of a novel micro
      nanofluidic device for a fast and efficient, continuous-flow, and virtually label
      free detection/purification protocol that goes beyond the standard methods of
      electrophoretic mobility shift assays, capillary electrophoresis and affinity
      chromatography. Based on dielectrophoretic trapping, analyte mixtures of small
      linear DNA-fragments (2.868 kbp and 6.0 kbp), topological DNA variants like
      plasmids (6.766 kbp) and minicircle-DNA (2.257 kbp), or cytostatic- and protein
      DNA complexes were separated in the vicinity of a channel-spanning bowed ridge
      (creating a nanoslit). One analyte is continuously deflected due to
      dielectrophoretic trapping at the ridge whereas other species pass the nanoslit
      unhindered, resulting in two molecule specific pathways with baseline separated
      resolution. This offers one-step real-time separation of low analyte volumes on a
      one-minute timescale at low-costs. The underlying dielectrophoretic mechanism was
      quantified by determining the electrical polarizabilities of the molecules.
      Additionally, we compared the continuous-flow detection of DNA-complexes with
      well-established electrophoretic mobility shift assays. Future analytical and
      preparative applications, such as for plasmid pharmaceuticals as well as
      continuous sample harvesting in parallel microchip format, are discussed.

PMID- 23139930
TI  - Methylation-blocked enzymatic recycling amplification for highly sensitive
      fluorescence sensing of DNA methyltransferase activity.
AB  - Herein, using DNA adenine methylation (Dam) methyltransferase (MTase) as a model
      analyte, a novel fluorescence sensing strategy was developed for facile, rapid
      and highly sensitive detection of the activity and inhibition of the target based
      on methylation-blocked enzymatic recycling amplification. In this sensing system,
      nicking endonuclease Nt.AlwI with the methylation-sensitive property was selected
      to achieve signal amplification. In addition, a DNA heteroduplex probe is
      specially designed to contain the recognition sequences for both Dam MTase and
      Nt.AlwI. In the absence of Dam MTase, Nt.AlwI cleaves the DNA heteroduplex at
      only the top strand. At the reaction temperature, the cleaved heteroduplex is
      unstable and readily separates. The released bottom strand can hybridize with the
      molecular beacons (MB) and subsequently trigger Nt.AlwI-mediated recycling
      cleavage of MBs, providing a dramatically amplified fluorescence signal. However,
      when the heteroduplex is methylated by Dam MTase, the cleaving operation is
      blocked, resulting in an inconspicuous fluorescence enhancement. Unlike existing
      signal amplified assays which use at least two enzymes, only one is involved in
      this amplified strategy. Under optimized conditions, the sensing system reveals a
      detection limit of 0.05 U mL(-1) in a short assay time (65 min), which is much
      superior to all presently reported methods except for two electrochemical
      biosensors (0.04 U mL(-1)). Furthermore, the application of the assay in human
      serum and screening of Dam MTase inhibition were demonstrated with satisfactory
      results. Overall, the proposed sensing system shows great potential for further
      application in biological research, early clinical diagnosis and designed drug
      therapy.

PMID- 23139929
TI  - Portable ceria nanoparticle-based assay for rapid detection of food antioxidants
      (NanoCerac).
AB  - With increased awareness of nutrition and the advocacy for healthier food
      choices, there exists a great demand for a simple, easy-to-use test that can
      reliably measure the antioxidant capacity of dietary products. We report
      development and characterization of a portable nanoparticle based-assay, similar
      to a small sensor patch, for rapid and sensitive detection of food antioxidants.
      The assay is based on the use of immobilized ceria nanoparticles, which change
      color after interaction with antioxidants by means of redox and surface chemistry
      reactions. Monitoring corresponding optical changes enables sensitive detection
      of antioxidants in which the nanoceria provides an optical 'signature' of
      antioxidant power, while the antioxidants act as reducing agents. The sensor has
      been tested for the detection of common antioxidant compounds including ascorbic
      acid, gallic acid, vanillic acid, quercetin, caffeic acid, and epigallocatechin
      gallate and its function has been successfully applied for the assessment of
      antioxidant activity in real samples (teas and medicinal mushrooms). The
      colorimetric response was concentration dependent, with detection limits ranging
      from 20 to 400 MUM depending on the antioxidant involved. Steady-state color
      intensity was achieved within seconds upon addition of antioxidants. The results
      are presented in terms of Gallic Acid Equivalents (GAE). The sensor performed
      favorably when compared with commonly used antioxidant detection methods. This
      assay is particularly appealing for remote sensing applications, where
      specialized equipment is not available, and also for high throughput analysis of
      a large number of samples. Potential applications for antioxidant detection in
      remote locations are envisioned.

PMID- 23139932
TI  - Photo- and electrochromic properties of covalently connected symmetrical and
      unsymmetrical spiropyran-polyoxometalate dyads.
AB  - Polyoxometalates covalently linked to one or two spiropyran entities have been
      isolated. These organic-inorganic hybrids exhibit multi-electrochromic and
      photochromic properties.

PMID- 23139931
TI  - 3,5-Diformyl-borondipyrromethene for selective detection of cyanide anion.
AB  - Cyanide is one of the most toxic inorganic anions, it is very harmful to human
      health but extremely useful in industrial activities. Herein, we used our
      recently reported boradiazaindacene (BODIPY) dye, 3,5-diformyl
      borondipyrromethene (BODIPY 1) as an exclusive chemodosimetric and colorimetric
      sensor for CN(-) ion. Cyanide ion attacks the carbonyl groups of 1 via a
      nucleophilic addition reaction and converts to cyanohydrin which is reflected in
      the clear colour change as well as by the absorption, emission and
      electrochemical properties. Thus BODIPY 1 can be used as a colorimetric and
      chemodosimetric sensor for CN(-) ion. Furthermore, to show that the position of
      the formyl group on BODIPY plays an important role in the ability of BODIPY dye
      to act as a chemodosimetric sensor for CN(-) ion, we synthesized another formyl
      group containing BODIPY dye, 3, in which the formyl group is present at the para
      position of the meso-phenyl group. (1)H NMR studies confirmed the formation of
      the cyanohydrin form of BODIPY dye 3 on addition of CN(-) ion but dye 3 cannot be
      used as a chemodosimetric sensor for CN(-) ion, as verified by absorption and
      fluorescence studies. The detection of cyanide with BODIPY dye 1 for biological
      application was also performed in MDA-MB-231 cells.

PMID- 23139933
TI  - Overcoming the solvation shell during the crystallisation of diatrizoic acid from
      dimethylsulfoxide.
AB  - We present three crystal structures of diatrizoic acid (DTA) DMSO solvates
      illustrating progressive desolvation of the DTA molecule and concomitant
      increasing degree of DTA self-association. Using these structures, plausible
      pathways for overcoming the solvation shell of DTA during its crystallisation
      from solution are discussed.

PMID- 23139934
TI  - A biocatalytic hydrogenation of carboxylic acids.
AB  - The hyperthermophile Pyrococcus furiosus catalyses the hydrogenation of a broad
      range of carboxylic acids selectively to the corresponding primary alcohols.
      Other functional groups such as isolated C=C-double bonds are not touched. The
      chemoselectivity of the carboxylate reduction may be directed towards aldehydes
      by simple medium engineering.

PMID- 23139935
TI  - A multimodal, beta-amyloid-targeted contrast agent.
AB  - A multimodal, beta-amyloid-targeted contrast agent was synthesized and studied in
      vitro. The agent has a higher relaxivity than a clinically approved contrast
      agent and interacts with beta-amyloid aggregates producing changes in relaxation
      rate and fluorescence emission.

PMID- 23139936
TI  - Activation of molecular oxygen by a metal-organic framework with open 2,2'
      bipyridine for selective oxidation of saturated hydrocarbons.
AB  - A metal-organic framework with open 2,2'-bipyridine sites can efficiently
      activate molecular oxygen for selective oxidation of a variety of saturated
      hydrocarbons with unprecedented activities and selectivities.

PMID- 23139937
TI  - Oculomotor and gait disturbance during pregnancy.

PMID- 23139938
TI  - Brainstem syndrome in a man with diabetes receiving haemodialysis.

PMID- 23139939
TI  - Biomedical research: Texas potential.

PMID- 23139940
TI  - Ignition switch.

PMID- 23139941
TI  - Science aid.

PMID- 23139942
TI  - John Maddox prize.

PMID- 23139943
TI  - Mood, menopause and hysterectomy.

PMID- 23139944
TI  - [Q & A. Acute cholecystitis in a 13-year-old boy?].

PMID- 23139945
TI  - Veterans' Group Life Insurance (VGLI) no-health period extension. Final rule.
AB  - The Department of Veterans Affairs (VA) is issuing this final rule that amends
      the regulations governing eligibility for Veterans' Group Life Insurance (VGLI)
      to extend to 240 days the current 120-day "no-health" period during which
      veterans can apply for VGLI without proving that they are in good health for
      insurance purposes. The purpose of this rule is to increase the opportunities for
      disabled veterans to enroll in VGLI, some of whom would not qualify for VGLI
      coverage under existing provisions. This document adopts as a final rule, without
      change, the proposed rule published in the Federal Register on June 25, 2012.

PMID- 23139946
TI  - Medicaid program; payments for services furnished by certain primary care
      physicians and charges for vaccine administration under the Vaccines for Children
      program. Final rule.
AB  - This final rule implements Medicaid payment for primary care services furnished
      by certain physicians in calendar years (CYs) 2013 and 2014 at rates not less
      than the Medicare rates in effect in those CYs or, if greater, the payment rates
      that would be applicable in those CYs using the CY 2009 Medicare physician fee
      schedule conversion factor. This minimum payment level applies to specified
      primary care services furnished by a physician with a specialty designation of
      family medicine, general internal medicine, or pediatric medicine, and also
      applies to services rendered by these provider types paid by Medicaid managed
      care plans contracted by states to provide the primary care services. It also
      provides for 100 percent federal financial participation (FFP) for any increase
      in payment above the amounts that would be due for these services under the
      provisions of the approved Medicaid state plan, as of July 1, 2009. In other
      words, there will not be any additional cost to states for payments above the
      amount required by the 2009 rate methodology. In this final rule, we specify
      which services and types of physicians qualify for the minimum payment level in
      CYs 2013 and 2014, and the method for calculating the payment amount and any
      increase for which increased federal funding is due. In addition, this final rule
      will update the interim regional maximum fees that providers may charge for the
      administration of pediatric vaccines to federally vaccine-eligible children under
      the Pediatric Immunization Distribution Program, more commonly known as the
      Vaccines for Children (VFC) program.

PMID- 23139947
TI  - Medicare program; Home Health Prospective Payment System rate update for calendar
      year 2013, hospice quality reporting requirements, and survey and enforcement
      requirements for home health agencies. Final rule.
AB  - This final rule updates the Home Health Prospective Payment System (HH PPS)
      rates, including the national standardized 60-day episode rates, the national per
      visit rates, the low-utilization payment amount (LUPA), the non-routine medical
      supplies (NRS) conversion factor, and outlier payments under the Medicare
      prospective payment system for home health agencies effective January 1, 2013.
      This rule also establishes requirements for the Home Health and Hospice quality
      reporting programs. This final rule will also establish requirements for
      unannounced, standard and extended surveys of home health agencies (HHAs) and
      sets forth alternative sanctions that could be imposed instead of, or in addition
      to, termination of the HHA's participation in the Medicare program, which could
      remain in effect up to a maximum of 6 months, until an HHA achieves compliance
      with the HHA Conditions of Participation (CoPs) or until the HHA's provider
      agreement is terminated.

PMID- 23139948
TI  - Medicare program; end-stage renal disease prospective payment system, quality
      incentive program, and bad debt reductions for all Medicare providers. Final
      rule.
AB  - This final rule updates and makes revisions to the end-stage renal disease (ESRD)
      prospective payment system (PPS) for calendar year (CY) 2013. This rule also sets
      forth requirements for the ESRD quality incentive program (QIP), including for
      payment year (PY) 2015 and beyond. In addition, this rule implements changes to
      bad debt reimbursement for all Medicare providers, suppliers, and other entities
      eligible to receive Medicare payment for bad debt and removes the cap on bad debt
      reimbursement to ESRD facilities. (See the Table of Contents for a listing of the
      specific issues addressed in this final rule.)

PMID- 23139949
TI  - Retraction: The latent structure of the Peritraumatic Dissociative Experiences
      Questionnaire.

PMID- 23139950
TI  - Outbreak news. Ebola, Democratic Republic of the Congo.

PMID- 23139951
TI  - Review of the 2012 winter influenza season, southern hemisphere.

PMID- 23139952
TI  - Global routine vaccination coverage,2011.

PMID- 23139953
TI  - Outbreak news. Marburg haemorrhagic fever, Uganda.

PMID- 23139954
TI  - Outbreak news. Rift Valley fever, Mauritania.

PMID- 23139955
TI  - Progress towards poliomyelitis eradication, Nigeria, January 2011- September
      2012.

PMID- 23139956
TI  - Monthly report on dracunculiasis cases, January-September 2012.

PMID- 23139957
TI  - Perceptions of AIDS risk and condom use among out-of-school adolescents in Moshi
      rural district, northern Tanzania.
AB  - OBJECTIVE: To determine the magnitude of perceived AIDS risk among out-of-school
      adolescents in Moshi rural district of Kilimanjaro region, northern Tanzania.
      METHODS: A cross-sectional study involving face-to-face interviews with out-of
      school adolescents in eleven rural villages in Moshi district, northern Tanzania.
      RESULTS: We found that of the 668 adolescents (10-19 years of age) surveyed,
      45.4% were sexually active and significantly more men than women reported being
      sexually active (55.85 versus 23.0%, OR = 0.24, 95% CI = 0.16 to 0.34).
      Adolescents who had travelled to Moshi town or out of Tanzania were significantly
      more likely to be sexually active compared with those who have never travelled.
      Despite perception of AIDS risk, a large majority (70.5%) of sexually active
      adolescents reported having multiple sexual partners. Adolescents who perceived
      being at AIDS risk were less likely to report having multiple sexual partners and
      were more likely to report having used a condom at the last sexual intercourse.
      CONCLUSION: These findings indicate that adolescents in this rural population are
      still practising high risk sexual behaviours suggesting the need for youth
      targeted intervention programmes in rural Tanzania.

PMID- 23139958
TI  - Occurrence of extended spectrum beta (b)-lactamases in multi-drug resistant
      Escherichia coli isolated from a clinical setting in Jimma University Specialized
      Hospital, Jimma, southwest Ethiopia.
AB  - INTRODUCTION: Resistance to antibiotics has grave consequences leading to
      treatment failure and increased health care costs. This public health risk has
      become a global problem with some countries like Ethiopia seriously affected.
      Members of the family enterobacteriaceae, including E. coli, are among the most
      important human pathogens accounting for the majority of bacterial strains
      isolated from clinical patient samples. Moreover, there is insufficient data
      regarding Extended-spectrum Beta-lactamase (ESBL) prevalence among Escherichia
      coli strains from Ethiopia. Thus, the objective was to determine the production
      of ESBL among clinical isolates and assess the in vitro susceptibility of the E.
      coli to the routinely used selected antibiotics. METHODS: We collected a total of
      359 clinical specimens (56 urine, 116 sputum, 72 stool and 15 wound swabs) from
      in- and outpatients at Jimma University Specialised Hospital, Jimma zone,
      southwest Ethiopia. RESULTS: E. coli was isolated from 67 (18.66%) clinical
      specimens, of which 24 (36%) isolates were ESBL producers. The resistance pattern
      to the tested antibiotics was: penicillin (97%), amoxacillin and ampicillin
      (86.6% each), tetracycline (73.1%), amoxacillin-clavulanate (70.1%), co
      trimoxazole (56.7%), chloramphenicol (35.8%), ciprofloxacine (20.9%),
      norfloxacine (16.4%), cefotaxime (9%), ceftazidime (6%), gentamicin (3%). All the
      isolates tested showed resistance to two or more drugs, and were considered to be
      multi-drug resistant. CONCLUSION: A higher rate (46%) of ESBL production and
      multi-drug resistance was seen among isolates from inpatients as compared to
      outpatients (33%) at the hospital.

PMID- 23139959
TI  - The typology of female sex workers in Dar-es-Salaam: implications to HIV and AIDS
      interventions targeting female sex workers in Tanzania.
AB  - OBJECTIVE: To establish the categories of female sex workers in Dar es Salaam.
      METHODS: We conducted in depth-interviews with 32 female sex workers (FSWs) in
      five geographic areas of Dar-es-Salaam known to be the primary residential and
      working places, three local government leaders in three of the five areas known
      to have brothels and two NGO representatives working with this population.
      RESULTS: There are about 14 categories of FSWs with fluid perceived 'boundaries',
      which could change given factors like the availability of clients, active
      prostitution control mechanisms, the weather, the female sex worker's need for
      money and the type of sexual services demanded. CONCLUSIONS: different categories
      provided by the study participants are only useful in the Dar-es-Salaam context
      but generalization to other places in Tanzania might not be quite possible.
      However, using these classifications provides an understanding of how they
      construct their real world with regard to sex work, experiences, (health) needs
      and shared characteristics that are important when planning for all aspects of
      research designs and the implementation of interventions targeting them. The
      Ministry of Health and Social Welfare (MoHSW), through the National AIDS Control
      Program (NACP), stakeholders and development partners should conduct more
      research in this area to generate more information that would facilitate lobbying
      and advocating for repealing colonial-rooted anti-prostitution laws and replacing
      them with policies aiming at assisting them.

PMID- 23139960
TI  - Hypertension control and other cardiovascular risk factors among diabetic
      patients at Muhimbili National Hospital, Tanzania.
AB  - BACKGROUND: Hypertension among diabetics is a well recognized cardiovascular risk
      factor. This study aimed at determining the prevalence of hypertension, its
      control and the prevalence of other cardiovascular risk factors among diabetic
      patients. METHODS: We consecutively enrolled 150 adult diabetics. Their age, sex
      weight, height, blood pressure, fasting capillary blood glucose, lipid and renal
      profiles, hypertension and diabetes therapy were ascertained. RESULTS:
      Hypertension prevalence was 54.7%. Treatment and control rates of hypertension
      were 81.7% and 34% respectively. Hypertensive patients were older, more
      overweight/obese, had a longer duration of diabetes and elevated serum
      creatinine. The prevalence of Dyslipidemia, overweight and obesity were 88%,
      48.7% and 18.7% respectively. Poor diabetes control was observed in 76.7% of
      patients. Cigarette smoking was uncommon. CONCLUSION: Hypertension,
      hyperglycemia, dyslipidemia and obesity are prevalent among our diabetic
      patients. Both hypertension and glycemia were poorly controlled. Addressing
      individuals' global cardiovascular risk profiles is vital in diabetics.

PMID- 23139961
TI  - Exploration of knowledge, attitudes and behaviours of street children on the
      prevention of HIV and AIDS in the Huye district, Rwanda.
AB  - HIV and AIDS is a pandemic that continues to ravage humanity worldwide,
      especially among the youth. Street children are victims of society and are up to
      10-25 times more affected by HIV and AIDS than their counterparts who live with
      their families. OBJECTIVES: The purpose of the study was to explore the
      knowledge, attitudes and behaviors of street children with regard to the
      prevention of HIV and AIDS. METHODS: A cross sectional study with a quantitative
      approach was carried out in two street children centres in the Huye district,
      which is situated in the Southern Province of Rwanda. Non probability convenience
      sampling was used and 83 participants between the ages of 10 and 18 years old
      were invited to participate. These comprised of 43 females (51.8%) and 40 males
      (48.2%), A questionnaire, which was translated into Kinyarwanda, was used to
      collect data from the participants. RESULTS: The findings indicated that the
      knowledge level of the participants was moderate at 71.7%. However, they still
      had misconceptions regarding HIV and AIDS as 16.9% of the participants said that
      there is a vaccine for HIV and AIDS and that it is curable. While 78.3% of the
      participants knew that HIV could be transmitted by body fluids, only 45.8% and
      49.4% knew that it could be transmitted by oral sex and anal sex respectively.
      The current study revealed that 36.1% of the participants were currently sexually
      active and 53.7% had not used a condom during their last sexual intercourse. A
      total of 21.7% of the participants had been given money; drugs or place to sleep
      in exchange for sex and 20.7% declared that they had unwillingly been forced to
      have sex. CONCLUSIONS: It is evident that although street children have a
      moderate knowledge level about HIV and AIDS, they still have certain
      misconceptions and are exposed to HIV and AIDS due to their risky behaviours. The
      health professionals should implement a programme of HIV and AIDS prevention
      among street children so that the street children life may be saved.

PMID- 23139962
TI  - Utilisation of delivery services in Zaria, northern Nigeria: factors affecting
      choice of place of delivery.
AB  - AIM: To determine the effect of companionship during labour and delivery, and the
      preferred delivery position, on the choice of place of delivery among women in
      Zaria, with a view to providing more acceptable services. METHODS: 315 consenting
      women attending the antenatal clinic at primary health facility in Zaria were
      interviewed. RESULTS: 62.24% of the women had their last delivery at home.
      Reasons for not wanting to deliver in health facility included the fact that it
      was too expensive (48.19%), concern that a companion would not be allowed to stay
      with them during labour and delivery (12.05%), unfriendly healthcare providers
      (10.84%), and concern about not being allowed to deliver in their preferred
      position (4.82%). CONCLUSION: Women in Zaria value social support and freedom to
      decide the position to adopt during labour and delivery. Healthcare providers and
      policy makers need to be sensitive to such needs that affect uptake of services.

PMID- 23139963
TI  - Substandard and counterfeit antimicrobials: recent trends and implications to key
      public health interventions in developing countries.
AB  - OBJECTIVE: The objective of this review is to produce evidence on the prevalence
      and trends in the availability of substandard and counterfeit antimicrobials in
      the global market and its consequences on key public health interventions in
      developing countries METHODS: Review of various literatures collected through the
      internet and other sources. Literature search using PubMed and Medline databases
      and Google search engine was conducted to identify related publications on the
      subject. Relevant published and unpublished literature was also consulted as
      additional source of information. RESULTS: During the past few decades, the trade
      of substandard and counterfeit medicines has increased substantially. Past
      experiences indicate that almost any kind of medicine can be counterfeited. In
      developing countries, primary targets are those antimicrobials that are commonly
      used in the treatment of life-threatening conditions including malaria,
      tuberculosis and HIV/AIDS. The findings in this review support the strong
      contention that substandard and counterfeit antimicrobials are available in the
      developing world in very high proportions. This is becoming one of the major
      causes of treatment failures leading to excessive mortality and morbidity.
      Moreover, it is implicated for contributing to the development of drug resistant
      organisms in many infectious diseases of public health significance such as
      malaria, tuberculosis and HIV/AIDS. CONCLUSION: If trends in the prevalence of
      counterfeit/substandard drugs continue at the current scale, there is a huge
      threat to interventions underway on major killer diseases in the developing
      world. So, public health interventions in developing countries should include
      quality control of antimicrobials as an integral part of program implementation.
      The national drug regulatory authorities in those countries should also be
      strengthened to enhance their capacity in enforcing regulations pertaining the
      registration, production, distribution and use of antimicrobial drugs.

PMID- 23139964
TI  - Strengthening paediatric emergency medicine in Pakistan is our need to reach
      millennium development goal 4.

PMID- 23139965
TI  - The prognostic value of the P53 protein and the Ki67 marker in breast cancer
      patients.
AB  - OBJECTIVE: To investigate and compare the prognostic value of P53 and Ki67
      markers in patients with breast cancer in Sabzevar, north east of Iran. METHODS:
      A descriptive analytical study was conducted on 80 patients with breast cancer
      who were admitted to the hospitals in Sabzevar in 2006 and they were followed up
      to 2010. The expression of ki67 and stability of p53 genes were determined by
      immunohistochemistry. To assess the disease prognosis, patients were followed up
      to 48 months. Data were analyzed using SPSS software version 11.5. Chi-square,
      Fisher's exact test, Kaplan-Miere and Log Rank tests were used for statistical
      purposes. RESULTS: Eighty cancerous tissue samples were examined. The Ki67 marker
      was present in 37 (46.3%) cases and the P53 protein stability in 39 (48.8%) cases
      were observed. There was a significant relationship between ki67 gene expression
      and tumour stage (p = 0.001) or tumour type (P = 0.02). There was also a
      significant relationship between the survival rate and the tumor stage (P =
      0.008). The Ki67 marker had significant relationship with the survival rate (P =
      0.031), but over expression of P53 protein did not show such significance (P =
      0.385). CONCLUSION: The results showed that the Ki67 marker was more important
      than P53 protein in prognosis of the breast cancer patients.

PMID- 23139966
TI  - Low-dose thalidomide in patients with metastatic renal cell carcinoma.
AB  - OBJECTIVE: To evaluate the role of thalidomide in patients with metastic renal
      cell carcinoma and the efficacy, toxicity and response rates to thalidomide.
      METHODS: The phase-II clinical trial study was conducted at the Sindh Institute
      of Urology and Transplantation (SIUT), Karachi between November 2008, and April
      2009, comprising 80 patients with metastic renal cell carcinoma who had either
      progressed on or were not suitable for immunotherapy/biologic therapy. After
      institutional approval and informed consent, the patients received thalidomide
      400mg daily. Thalidomide was continued until the time of disease progression or
      documented severe toxicity. Primary endpoints were the safety, response,
      progression free survival (PFS) and overall survival (OS). SPSS version 16.0 was
      used for statistical analysis. RESULTS: The median follow-up was 18 months (15
      20); median age was 51.11 years (range 23-73). Three were 59 (73.8%) males. The
      bone (n=83; 47.5%), lungs (n=26; 32.5%) and lymph nodes (n=8; 10%) were frequent
      sites of distant metastases. Of the patients, 32 (40%) had previous different
      systemic treatments. Grade 3 and 4 toxicities were; fatigue (n=34; 42.5%),
      sensory neuropathy (n=8; 10%), deep venous thrombosis (n=7; 8.8%) and
      gastrointestinal upset (n=6; 7.5%). Response rates were available for 75
      patients: partial 48 (60%); stable disease 12 (15%); progression 15 (18.8%);
      while 5 (6.2%) were not evaluated. Median progression free survival and overall
      survival rates were 7 months and 19 months respectively. CONCLUSION: Low-dose
      thalidomide resulted in manageable toxicity, better response rates, progression
      free survival and overall survival in the study population. Further large
      randomised trials are warranted.

PMID- 23139967
TI  - CT guided percutaneous renal biopsy versus ultrasound guided for obtaining
      adequate tissue.
AB  - OBJECTIVE: To study the diagnostic yield of specimen obtained by percutaneous
      renal biopsy (PRB) under CT guidance and Ultrasound (US) guidance. METHODS: This
      study was conducted at the department of Nephrology at Liaquat National Hospital
      and Dr. Ziauddin Hospital, Karachi. Renal biopsy specimens obtained between
      January 2007 and September 2009 were studied for number of glomeruli obtained. In
      addition data was collected of how many patients had to undergo renal biopsy
      again because of nonavailability of renal cortex (the area of the kidney that
      contains glomeruli necessary for diagnosing renal disease) by both methods.
      RESULTS: We analyzed 205 renal biopsy specimens. Fifty were obtained via CT and
      155 under US guidance. All 50 specimens obtained by CT guidance had renal cortex,
      compared to 147/155 (94.8%) specimen obtained by US guidance. Mean number of
      glomeruli in US guided specimens was 10.28 +/- 6.85, compared to CT guided
      specimen which was 23.34 +/- 13.42. Definitive diagnosis was made in 100% of CT
      guided biopsy compared to 94.8% (p<0.001) in US guided specimens. None of the
      patients undergoing CT guided biopsy required re-biopsy. CONCLUSION: PRB of
      native kidney under CT guidance is a more effective tool compared to ultrasound
      guidance in obtaining renal cortex that prevents patients from undergoing biopsy
      twice and provides sufficient number of glomeruli for definitive diagnosis of
      renal diseases especially when focal disease is suspected.

PMID- 23139968
TI  - Differences in various measurements on panoramic radiograph among erupted and
      impacted lower third molar groups.
AB  - OBJECTIVE: To determine the differences in various linear and angular
      measurements between erupted and impacted lower third molar group on conventional
      panoramic radiographs. METHODS: The quasi-experimental study based on non
      probability convenience sampling and done at the National Institute of Oral
      Diseases, Karachi, comprised 140 patients having full dentition with bilaterally
      present mandibular third molars varying between ages of 18-30 years. After
      clinical examination, 280 lower third molars were divided into two groups; Group
      A had erupted, while Group B comprised impacted mandibular third molars. All
      radiographs were traced and measured for five variables to compare the two
      groups. For statistical purpose, SPSS version 10, and t test were used. RESULTS:
      Retromolar space measured from Xi (centre of ramus) was 31.60 +/- 3.33 mm in
      Group A and 27.02 +/- 4.17mm in Group B. Retromolar space measured from anterior
      edge of ramus (AER) was 16.30 +/- 2.51 mm in Group A and 11.21 +/- 3.69 in Group
      B. Mesiodistal width was 13.39 +/- 1.44mm in Group A and 13.80 +/- 1.58 in Group
      B. Retromolar space/width ratio was 1.22 +/- 0.20 for Group A and 0.82 +/- 0.34
      for Group B. Mean angulations in Group A was 5.98 +/- 5.9 degrees whereas 34.56
      +/- 27.89 degrees in Group B. CONCLUSION: The probability of eruption of the
      lower third molar increases if retromolar space measured from anterior edge of
      ramus (AER-7) and centre of rumus point (Xi-7) is 13mm and 25mm respectively,
      provided the space/width ratio is greater than 1 and angulation is also vertical.
      Mesiodistal width of the tooth has no significant role in impactions.

PMID- 23139969
TI  - Cryopreservation of embryos by vitrification at a private sector reproductive
      medicine facility in Karachi.
AB  - OBJECTIVE: To assess the survival of freezing cleaved human embryos through
      vitrification. METHODS: The prospective study was conducted at the Karachi-based
      Sindh Institute of Reproductive Medicine between June 2008 and June 2009. The
      cryopreservation of embryos being a new technology in Pakistan, only 19 couples,
      picked through convenience sampling, comprised the study population. The couples
      were treated for infertility by in virto fertilisation (IVF) or intracytoplasmic
      sperm injection (ICSI); 125 surplus embryos were vitrified. Subsequently, 15
      embryos were thawed, and transferred in a controlled cycle. SPSS version 11 was
      used for statistical analysis. RESULT: After the surplus embryos were vitrified
      and subsequently thawed and transferred, the survival of the embryos was assessed
      by the number of blastomeres that were intact. The overall embryo survival rate
      was (14/15) 93.33%. CONCLUSION: Vitrification is a simple procedure that requires
      less time and is likely to become safer and more cost-effective with time.
      Survival rate after thawing and preserving is high, but comparative success rates
      in terms of pregnancy and taking-home-baby rates are yet to be established in
      Pakistan.

PMID- 23139970
TI  - Tubed vs tubeless PCNL in children.
AB  - OBJECTIVE: To compare post-operative outcomes between tubeless and conventional
      large-bore nephrostomy tube drainage following percutaneous nephrolithotomy in
      children. METHODS: The study comprised 54 patients under 14 years of age who were
      undergoing percutaneous nephrolithotomy at 60 renal units and met the inclusion
      criteria. They were randomised to placement of a 16F nephrostomy tube (Group A,
      30 renal units) or tubeless drainage (Group B, 30 renal units) at the end of the
      procedure. Patient age, number and position of stones, operating time, change in
      haemoglobin, post-operative analgesia requirement, length of hospital stay and
      post-operative complications were compared between the two groups, using SPSS
      version 17 and t test. RESULTS: Group A had 28 patients, while Group B had 26.
      The mean age in Group A was 7.2 +/- 3.2 years, and in Group B it was 6.3 +/- 3.6
      years (age range 3-13 years and 1-13 years respectively). The mean size of stone
      was 28.6 +/- 16.7mm and 20.4 +/- 9.3mm; mean change in Hb was 0.78 +/- 0.69mg/dl
      and 0.63 +/- 0.54mg/dl; and the mean operating time was 54 +/- 20.7 minutes
      versus 66.9 +/- 22.9 minutes in the two groups respectively. There was
      significantly less requirement for post-operative pethidine in Group B versus
      Group A (p=0.01). The postoperative clearance and complications were comparable
      between the two groups, while the duration of hospital stay was significantly
      shorter in Group B compared to Group A (p=0.007). CONCLUSION: Tubeless
      percutaneous nephrolithotomy in children is safe and effective. Post-operative
      analgesia requirement is less and hospital stay is shortened compared to the
      conventional nephrostomy placement after percutaneous nephrolithotomy.

PMID- 23139971
TI  - Frequency of tracheobronchial foreign bodies and their management in urban
      population of Sindh.
AB  - OBJECTIVE: To assess the common foreign bodies in urban areas of Sindh, and the
      presentation, problems and complications during their removal through rigid
      bronchoscopy. METHODS: The descriptive study was conducted at the Ear, Nose and
      Throat Department and the Department of Head and Neck Surgery of Liaquat
      University Hospital, Hyderabad, and Abbasi Shaheed Hospital, Karachi, from April
      2009 to October 2010. Fifty patients with strong suspicion of foreign body
      inhalation in whom rigid bronchoscopy was done were included in the study. A
      definitive diagnostic protocol was applied and rigid bronchoscopy was done to
      search and remove the foreign bodies. The data was fed into SPSS version 15 for
      descriptive analysis. RESULTS: In our study,28(56%) cases were male and 22(44%)
      were female. The age range was 1-7 years. Most of the victims (n=21; 42%) were
      over 3 years of age. Commonest symptom of presentation was dyspnoea (n=34; 68%)
      and the commonest sign of presentation was decreased unilateral air entry (n=25;
      50%). Most of the foreign bodies were impacted in the right main bronchus (n=26;
      52%). The most retrieved foreign body was betel nut (n=23; 46%). The commonest
      complication of bronchoscopy was airway oedema which occurred in 13 (26%)
      patients. The successful removal of exogenous foreign body was achieved in 41
      (82%), and the mortality rate was 3 (6%). CONCLUSION: Delay in the diagnosis of
      foreign body inhalation translates into a higher risk of complications.
      Therefore, early bronchoscopy should be done on suspicion. Early recognition at
      both parental and clinical levels should be promoted through public awareness.

PMID- 23139972
TI  - Medically certified sickness absence among health care workers.
AB  - OBJECTIVES: To compare the days and spells of sickness absence among males versus
      females and Saudi nationals versus expatriate employees of King Khalid University
      Hospital, Riyadh, and to identify the cause of sickness absence. METHODS: The
      cross-sectional, descriptive study comprised 3117 King Khalid University Hospital
      employees. Records of physician-certified sickness absence from January 1 to June
      30, 2009, were obtained from the employee health clinic's register. Absence rate,
      frequency, duration and severity were assessed and compared between genders and
      nationalities, and causes were noted. SPSS version 16 and student's t test were
      used for statistical analyses and comparison. RESULT: A total of 377 (12.1 %)
      employees had 416 spells of sickness absence with 639 sick-off days (mean: 1.54
      +/- 0.85). The probability of sickness absence was higher among Saudi (OR=1.33)
      and female (OR=1.39) employees. The association of sickness absence was not found
      among the absentees with either gender (p= 0.335) or nationality (p = 0.086).
      Almost all spells of sick-off days were of short duration. Longer spells were
      mainly due to chicken pox which was found to be more among the expatriates. Heavy
      absenteeism was found only among the Saudis. The most common causes of sickness
      absence were acute upper respiratory infection, diseases of musculoskeletal
      system and the digestive system. CONCLUSION: The rate, frequency and duration of
      absence due to sickness in the study were higher among Saudi and female
      employees. The rate of absence, with passage of time, has increased significantly
      among Saudi nationals.

PMID- 23139973
TI  - Psychosocial impact of cancer on adult patients.
AB  - OBJECTIVES: To explore the effects of cancer on psychosocial aspects of Pakistani
      patients and their families, assessing the need for interventions to improve
      their quality of life. METHODS: A prospective, Cross-sectional study was
      performed on 200 patients visiting the oncology outpatient facility of AKUH from
      December 2010 to May 2011 through an interview. Responses were recorded on pre
      designed questionnaires including FACT-G QOL (Functional Assessment of Cancer
      Therapy-General Quality Of Life) component. RESULTS: Out of the 200 patients 52
      (26%) were males and 148 (74%) were females. Mean age was 51.8 +/- 14.2 years.
      Breast cancer accounted for the commonest cancer in females 116 (58%) and lung in
      males 30 (15%), 100 (50%) patients were currently undergoing chemotherapy. In all
      148 (74%) patients were well aware of their diagnosis and were able to cope
      better and 142 (71%) were well supported by families (majority being financially
      stable). Major financial impact was found in 42 (21%) cases. Religious/spiritual
      help was sought by 138 (69%) patients predominantly females- 113 (76%) and 22
      (11%) patients consulted a psychiatrist; 20 (94%) subjects of this group felt
      this intervention was helpful. Responses regarding effect on the patient's sexual
      life were poor and 126 (63%) denied answering the question. CONCLUSION: In our
      study one third of cancer patients were found to be depressed mainly affecting
      those who were receiving multimodality treatment or facing financial issues.
      Religious help was the main coping strategy for them.

PMID- 23139974
TI  - Non fatal injuries among infants: a pilot study.
AB  - OBJECTIVE: To determine the incidence, nature and the extent of infant injuries
      in two suburban and rural communities of Pakistan. METHODS: The cross-sectional
      study was conducted on a cohort of 310 infants in suburban and rural communities
      of Pakistan in September 2007. The information was collected from primary care
      givers based on any injury that had occurred to their infants during the
      preceding 3 months that required treatment at home or in a hospital. RESULT: The
      incidence of non-fatal injury for infants up to 1-year-old was found to be 19
      injuries per 100 person (child) years of exposure (95% CI 9.90 - 27.21). In
      suburban area, the rate was 26 injuries/100 person (child) years (95 % CI 15.37 -
      35.71), while in rural area, it was 13 injuries/100 person (child) years of
      exposure (95 % CI 4.79-18.39). Altogether, 13 episodes of injury were reported
      among infants in both the communities. The male to female infant ratio for injury
      was 1:2.2. Suburban area had more than double injuries compared to the rural
      area. CONCLUSION: The magnitude of infant injuries was quite significant,
      especially among suburban and female children. There is a dire need to develop
      community-based interventions creating awareness on the matter.

PMID- 23139975
TI  - Faculty and patient evaluations of radiology residents' communication and
      interpersonal skills.
AB  - OBJECTIVE: To assess communication and interpersonal skills (CIS) of radiology
      residents through faculty and standardised patients (SP). METHODS: In this day
      long objective structured clinical examination (OSCE) in January 2009, 42
      radiology residents took part at six stations in Karachi, each with a
      standardised patient and a faculty evaluator. Each encounter lasted 15 minutes
      followed by independent assessments of the residents by both the evaluators.
      RESULTS: Based on rating-scale evaluations, all cases had satisfactory internal
      consistency (Cronbach's alpha 0.6 to 0.9). The alpha values were comparatively
      diminutive against the checklist scores. Correlation among faculty was 0.6
      (p<0.001) with the use of both the checklist and the rating scale. Among
      standardised patient, intra-class correlation was 0.6 (p<0.001) for checklists
      and 0.7 (p=0.001) for rating scales. Moderate to strong correlations (r=0.6 to
      0.9) existed between checklist and rating scores by the same type of evaluator.
      Correlations among the faculty and standardised patient using the same assessment
      tool were unimpressive. CONCLUSION: Both checklists and rating scales can serve
      as satisfactory assessment tools for communication and interpersonal skills using
      objective structured and clinical examination with the assistance of faculty and
      standardised patients.

PMID- 23139976
TI  - Role of small group interactive sessions in two different curriculums based
      medical colleges.
AB  - OBJECTIVE: To study students' perceptions of the usefulness of small group
      interactive sessions in medical colleges using conventional or problem based
      learning (PBL) teaching. METHODS: A cross sectional descriptive study was carried
      out from January 2010 to December 2010. Student's perception of the usefulness of
      small group interactive sessions (SGIS) was evaluated through a questionnaire
      filled by 100 first year MBBS students, each from two medical colleges using
      different teaching strategies. The colleges were labeled Group I, PBL Based
      Medical College (PBL-MC) and Group II; Conventional Medical College (CMC).
      Incomplete questionnaires (13 from Group 1 and 8 from Group 2 were excluded).
      Data were entered and compared using SPSS version 15. Differences were considered
      significant at p values<0.05 after application of chi square test. RESULTS:
      Responses of 179 students of Group I and II, revealed importance of small group
      interactive sessions in the understanding of content and facilitation in active
      learning. Significant difference in perception was found with respect to better
      interaction, confidence, clinical application and preparation for university
      examinations in CMC students. CONCLUSION: The importance of SGIS in learning of
      medical students cannot be overlooked in conventional teaching however in PBL-MC
      a combination of educational strategies can be employed for better learning of
      students.

PMID- 23139977
TI  - Percutaneous trans-jugular technique for continuous perioperative monitoring of
      intra-cardiac and pulmonary artery pressures during cardiac surgery for
      congenital heart disease.
AB  - OBJECTIVE: To observe the safety of trans-jugular pressure-monitoring catheter
      insertion at a tertiary care teaching hospital in Rawalpindi, Pakistan. METHODS:
      The observational study was carried out at the Armed Forces Institute of
      Cardiology/National Institute of Heart Diseases, Rawalpindi, from January 1, 2004
      to March 31, 2010. All patients electively scheduled to undergo cardiac surgery
      for congenital heart disease who had percutaneous trans-jugular pressure
      monitoring catheters inserted peri-operatively were included in the study.
      Dedicated Medtronic 3 Fr pressure monitoring catheters were passed through
      internal jugular vein using the modified Seldinger. The patients were followed up
      during the hospital stay for complications related to catheter insertion/removal.
      Data was analysed using SPSS version 15. RESULTS: Of the 572 patients in the
      study, the catheters were ultimately positioned with the tips in the pulmonary
      artery in 447 (78.14%)patients, right ventricle 54 (9.44%) patients, left atrium
      in 52 (9.09%), and in both pulmonary artery and left atrium in 19 (3.32%)
      patients. Duration of pressure monitoring from all the chambers was 53 +/- 19
      hours post-operatively. Transient and self-limiting atrial or ventricular ectopic
      beats were noticed in 163 (27.58%) patients during insertion. Catheter was found
      to be non-functional in 12 (2.03%) patients. Only one (0.16%) patient experienced
      recurrent tachyarrhythmia which required the withdrawal of catheter. CONCLUSION:
      Insertion of trans-jugular pressure monitoring catheters during cardiac surgery
      for congenital heart disease is a safe and reliable technique.

PMID- 23139978
TI  - Safety and effectiveness of biphasic insulin aspart 30 (Biasp 30) in people with
      type 2 diabetes mellitus in the pakistani population: results from the A1chieve
      study.
AB  - OBJECTIVE: To explore the safety and effectiveness of treatment with the insulin
      analogue, biphasic insulin aspart 30 (BIAsp 30), in people with type 2 diabetes
      mellitus (T2DM) in a subgroup of a Pakistani population from the A1chieve study.
      METHODS: A1chieve was a 24-week, international, prospective, multicentre, open
      label, observational, non-interventional study designed to evaluate the safety
      and clinical effectiveness of 66,726 people with T2DM who were initiated with
      basal insulin detemir, fast actinginsulin aspart, and BIAsp 30 (30% soluble
      insulin aspart, 70% protamine-crystallized insulin aspart). The study was
      conducted in 28 countries across Asia, Africa, Latin America, and Europe. Here,
      we report data from a subgroup of 762 people with T2DM from the Pakistani cohort
      (insulin naive and insulin users) who were treated withpremix insulin (BIAsp 30)
      +/- oral antidiabetic drugs (OADs). RESULTS: The decrease in HbAlc at week 24 was
      statistically significant in the entire cohort, the insulin naive, and insulin
      users (1.7 +/- 1.1%, 1.8 +/- 1.3% and 1.7 +/- 0.9%, respectively, p<0.001 for
      all).There was a statistically significant decrease in the mean fasting plasma
      glucose (FPG) and postprandial plasma glucose (PPG) from baseline toweek 24 in
      the entire cohort, in the insulin naive and in the insulin users with BIAsp 30
      treatment (p<0.001 for all).No major hypoglycaemic events were reported during
      the entire study period. There was a statistically significant decrease in the
      systolic blood pressure (SBP) in all groups (p<0.001). The improvement in the
      quality of life score (QoL)was statistically significant in all groups (p<0.001
      for all). CONCLUSION: BIAsp 30 treatment appeared to be well tolerated and
      effective as indicated byimproved glycaemiccontrol and QoL in people with T2DM in
      the Pakistani population after 24 weeks.

PMID- 23139979
TI  - Delivering endocrinology and reproduction in an integrated modular curriculum.
AB  - OBJECTIVE: To ascertain the perceptions of students and faculty of Shifa College
      of Medicine, Islamabad regarding the delivery of Endocrinology and Reproduction
      module as a component of the newly introduced Integrated Modular Curriculum.
      METHODS: A descriptive study, using mixed qualitative and quantitative method,
      starting from June 6 to August 15 2008. A period of 10 weeks was spent on the
      study including 8 weeks of planning, 2 weeks of delivery and assessment and a 2
      weeks period of post hoc analysis and data collection. A multidisciplinary team
      of faculty developed themes, clinical cases, objectives and table of
      specification of the Endocrinology and Reproduction Module for Fourth Year MBBS
      Class. Continuous assessment was done by theme-based assignments and student
      presentations. Summative assessment was done by Multiple Choice and Short Answer
      Questions. Likert scale-based student feedback questionnaire was administered
      while the students were also encouraged to comment on the module for improvement.
      Feedback was obtained from the faculty in a similar manner. RESULTS: Out of a
      class of 86 students, 47 (55%) agreed to a balance between basic and clinical
      concepts addressed in the module, 21 (24%) agreed that emphasis on clinical
      concepts was appropriate, 37 (43%) agreed that learning strategies were well
      integrated, 50 (58%) were of the opinion that the assigned learning material was
      consistent with the session objectives, while 39 (45%) agreed that case-based
      instruction was useful, and 40 (47%) students were of the opinion that large
      group discussion was useful. Faculty feedback was positive towards integrated
      learning. CONCLUSIONS: Integrated Endocrinology and Reproduction module received
      mixed response from students. This led us to modify and tailor the curriculum to
      better cater for the needs of students. Feedback from students and faculty is
      essential for improvement in the quality of educational interventions.

PMID- 23139980
TI  - Sexually transmitted infection care in pakistan: the providers perspective.
AB  - OBJECTIVE: To explore the healthcare providers' perspectives in the management of
      sexually transmitted infections. METHODS: The mixed-method qualitative study done
      in 2008 involved 51 general practitioners and specialists who are known among
      peers for managing sexually transmitted infections. Interviews were conducted
      using semi-structured instruments and recruitment was kept open within each
      provider type until specific themes were saturated. Providers were interviewed
      from 5 cities in Pakistan. RESULTS: Each type of provider was usually found
      dealing with a specific population sub-group. Nearly all providers were
      practising personal empiricism, rarely following any standardised guidelines.
      Testing for asymptomatic infections such as human immunodeficiency virus,
      syphilis or anal infections was rare as was counselling or partner management.
      CONCLUSION: Encounters with patients suffering from sexually transmitted
      infections seem to be missed opportunities to control community based
      transmission of such infections. Implementation research is needed to better
      understand how to induce healthcare providers to better manage these infections,
      test for asymptomatic infections and advise partner management.

PMID- 23139981
TI  - Acute appendicitis in the elderly; Pakistan Ordnance Factories Hospital, Wah
      Cantt. experience.
AB  - OBJECTIVE: To review the clinical experience in diagnosis, management and outcome
      of elderly patients presenting with acute appendicitis at the Pakistan Ordnance
      Factories Hospital, Wah Cantt. METHODS: All patients of age 60 years and above
      presenting with abdominal pain were prospectively reviewed. Patients who were
      diagnosed as acute appendicitis were included in this case series which was
      conducted at Pakistan Ordnance Factories Hospital, Wah Cantt, from December 2006
      to May 2008. Detailed history and clinical examination, co-morbid conditions,
      clinical manifestations and post-operative outcome were recorded. The diagnosis
      was made on the basis of history and clinical examination. The diagnosis was also
      confirmed on histopathology. All the details were recorded on a questionnaire.
      Approval from our own ethical committee was taken. SPSS 16 was used for
      statistical analysis. RESULTS: A total of 75 patients presented with acute
      abdominal pain. Of them 42 were admitted with tenderness in right iliac fossa and
      lower abdomen. Finally, 36 (48%) were diagnosed as acute appendicitis and were
      included in the study. There were 20(56%) men and 16(44%) women with age range of
      60 to 78 years and a mean age of 65.5 +/- 4.2 years. Associated illness occurred
      in 25(70%) patients. Symptoms included abdominal pain in 32(90%), nausea in
      17(48%), and emesis in 9(25%) patients. Signs included right lower quadrant
      tenderness in 26(74%) patients, leukocytosis in 17(47.2%), and fever (>99'F) in
      11(30.5%). Laparoscopy was used as an important diagnostic as well as therapeutic
      modality. Of the patients, 9 (25%) had gangrenous appendix, while 12 (33.3%) had
      perforated appendix. A total of 12 (33.4%) patients developed complications.
      Hospital stay was considerably increased in patients with a delayed diagnosis (5
      7 days), perforations (5-9 days) and postoperative complications (5-15 days). One
      patient, a known case of ischaemic heart disease, died of cardiopulmonary arrest.
      CONCLUSION: Acute appendicitis needs to be considered in the differential
      diagnosis of all patients with abdominal pain. A high index of suspicion is
      necessary to guard against mis-diagnosis, especially in the elderly. Delays in
      presentation and diagnosis are associated with higher rates of perforation and,
      hence, higher morbidity. Repeated clinical examination, a high index of suspicion
      and urgent investigations are necessary for a correct and rapid diagnosis.

PMID- 23139982
TI  - Reverse flow posterior interosseous flap: experience with 53 flaps at Nishtar
      Hospital, Multan.
AB  - OBJECTIVE: To assess the efficacy of reverse flow posterior interosseous artery
      flap for the coverage of large variety of hand/wrist defects. METHODS: The
      prospective study was conducted a the Department of Plastic Surgery and the Burns
      Unit of Nishtar Hospital, Multan, Pakistan, from June 2008 to June 2010. The
      study comprised 53 reverse flow posterior interosseous artery flaps in 50
      patients for the coverage of hand/wrist defects both in emergency and elective
      settings. Data was analysed using SPSS 10. RESULTS: The hand/wrist defects in the
      study population were caused by different etiologies. All the flaps survived in
      all the patients. Marginal loss over the distal edge of the flap was noted in one
      patient. Mild oedema developed in all patients, but it subsided except in one
      case. None of our cases showed any evidence of venous congestion. Regarding the
      donor site morbidity, only one case had partial STSG loss. Mean hospital stay
      post-flap coverage in the patients ranged from 7 to 21 days. CONCLUSION: Reverse
      flow posterior interosseous artery flap in experienced hands is safe, versatile
      and reliable for the coverage of hand/wrist defects.

PMID- 23139983
TI  - Epidemiological ins and outs of helicobacter pylori: a review.
AB  - Helicobacter pylori infection is now recognised as a worldwide problem. It is the
      most common cause of chronic gastritis, and is strongly linked to peptic ulcer
      disease and gastric cancer. A comprehensive understanding of epidemiological ins
      and outs of H. pylori infection is very important in solving the patho
      physiological enigma and might help in leading towards better management and
      prognosis of infection. This article presents a review of the literature on the
      epidemiology of H. pylori infection from 2006 to 2011. The authors used Medical
      Subject Heading (MeSH) terms 'Helicobacter' with 'epidemiology,' 'transmission'
      or 'risk factor' to search PubMed database. All relevant studies identified were
      included. Despite extensive medical advancement, many questions on Helicobacter
      pylori epidemiology still remain unanswered. Further studies are, therefore,
      required to gain a better understanding of the transmission pathway of this
      notorious pathogen.

PMID- 23139984
TI  - A segmental neurofibromatosis case with eruptive seborrheic keratoses.
AB  - Segmental neurofibromatosis (SNF) is a rare variant of neurofibromatosis (NF)
      type 1 characterized by a restricted distribution of cafe-au-lait macules, and/or
      neurofibromas, and rarely freckling to a single dermatomal segment. Patients with
      NF type 1 have an associated increased risk for benign or malignant tumours. The
      prevalence of typical NF type 1 complications including malignancies in SNF is
      much lower than the generalized form. Seborrheic keratosis is one of the more
      common benign epidermal tumour which can be a paraneoplastic syndrome when it
      arises with an eruptive appearance. To our knowledge in the literature no case of
      SNF associated with eruptive seborrheic keratoses has been defined. We report the
      case of a man, aged 51, who had SNF and abruptly developed eruptive seborrheic
      keratoses.

PMID- 23139985
TI  - Cystic adrenal lymphangioma--report of two cases and review of the literature.
AB  - Cystic adrenal lymphangiomas are very rare, benign vascular lesions. They are
      usually found during a work up for abdominal pain or incidentally during imaging
      studies for an unrelated cause. We report two cases of cystic adrenal
      lymphangiomas. They presented with flank discomfort, hypertension and flushing.
      Their laboratory findings were in normal limits. Radiologic imagings showed
      adrenal cystic neoplasm and the patients underwent adrenelectomy. Histopathologic
      examination and immunohistochemical findings were consistent with lymphangioma.
      Cystic lymphangiomas may imitate other adrenal neoplasms and must be kept in mind
      in the clinical and radiologic differential diagnosis of cystic adrenal lesions.

PMID- 23139986
TI  - Gallbladder volvulus.
AB  - Gallbladder volvulus or torsion; is an uncommon cause of acute abdomen and occurs
      by rotation of the gallbladder on its mesentery. The entity commonly misdiagnosed
      as cholecystitis before laparatomy, although it has some critical findings that
      alert physician for correct diagnosis. A 47 years old male patient admitted to
      our emergency department with right upper quadrant pain, and then progressed
      through abdominal rigidity indicating acute abdomen, was subjected to laparatomy.
      At surgery; gangrenous and rotated gallbladder was observed and cholecystectomy
      was performed. Early diagnosis and prompt surgical treatment is mandatory to
      lower the complications of this entity. Clinical signs and radiographic studies
      should guide physicians for proper diagnosis of gallbladder torsion.

PMID- 23139987
TI  - Tuberculous hypertrophic pachymeningitis presenting as visual blurring and
      headaches.
AB  - Hypertrophic cranial pachymeningitis is a rare chronic fibrosing inflammatory
      disease characterised by localized or diffuse thickening of duramater,
      leptomeninges, and tentorium. The etiology is diverse and includes infectious,
      granulomatous and inflammatory disorders, collagen vascular disorders, carcinoma,
      lymphoma, meningioma en plaque, sarcoidosis, haemodialysis,
      mucopolysaccharidosis, intrathecal drug administration, and meningeal
      carcinomatosis diseases. Intracranial hypotension is also an important image
      mimicker. Most often patients present with complaint of headache, vomiting,
      cranial nerve palsy, ataxia, raised intracranial pressure and focal neurological
      deficit. Other signs and symptoms are inconstant and variable. The imaging
      features of hypertrophic cranial pachymeningitis include dural thickening, dural
      mass, sinus thrombosis, venous congestion with white matter changes. Extensive
      preoperative imaging studies usually are essential by Computerised Tomography
      (CT) or Magnetic Resonance Imaging (MRI). The radiological findings may be
      characteristic of hypertrophic cranial pachymeningitis, may not divulge the
      underlying etiology. Meningeal biopsy is essential for diagnosing the cause. We
      reviewed a case of a tuberculous hypertrophic cranial pachymeningitis.

PMID- 23139988
TI  - A rare congenital cardiovascular abnormality presenting as respiratory distress
      in an infant.
AB  - Anomalous origin of left coronary artery from pulmonary artery (ALCAPA) is a rare
      congenital cardiovascular anomaly which presents in early infancy with congestive
      cardiac failure, sometimes precipitated by inter current respiratory tract
      infections. We report a case of an eight week old baby boy, with a short history
      of cough, difficulty in breathing, marked tachycardia and signs of respiratory
      distress. He was managed for bronchiolitis but eight hours later had major
      desaturation during feeding which needed intubation and mechanical ventilation.
      He improved over the next few hours and self extubated but after 12 hours needed
      reintubation and ventilation following a similar event of desaturation as
      observed previously. The chest x ray revealed cardiomegaly and diuretics were
      added in the on going management and he was gradually weaned off from the
      ventilator. The echocardiography examination revealed ALCAPA, resulting in
      myocardial ischaemia. Surgical revascularization was performed and baby was
      discharged after ten days on regular anti failure medication in a stable
      condition.

PMID- 23139989
TI  - Endoscopic repair of cerebrospinal fluid rhinorrhoea in a developing country.
AB  - The objectives of the study was to determine the causes and outcome of endoscopic
      repair of cerebrospinal fluid (CSF) leak in a developing country. A total of five
      patients were recruited in the study. The age of patients ranged from 8 to 65
      years. Four patients were male and one was female. In two cases of iatrogenic
      injury, the first was in the sphenoid sinus. The second was following functional
      endoscopic sinus surgery (FESS). Fascia lata was used to repair all cases.
      Beriplast was used as sealing agent in four cases and clotted blood was used in
      remaining case. Despite the small number, CSF rhinor rhoea was resolved in all
      cases. The patients were followed up for 2.5 to 6.5 years. Endoscopic repair is a
      viable option even in developing countries. It is cost effective and has a very
      low morbidity rate with no mortality at all.

PMID- 23139990
TI  - Obsessive-compulsive disorder (OCD): is this disorder under-recognized?

PMID- 23139991
TI  - What is better antiplatelet agent to prevent recurrent stroke?

PMID- 23139992
TI  - How to submit to a scientific journal and get published.

PMID- 23139993
TI  - Occupational injuries in welders--perspective from Faisalabad.

PMID- 23139994
TI  - Is the good cholesterol that good at preventing cardiac events?

PMID- 23139995
TI  - Measures used by medical students to reduce test anxiety.
AB  - OBJECTIVE: To determine test anxiety in medical students and to assess the
      measures used by them to reduce it. METHODS: The cross-sectional study was
      conducted in August 2009 at the Dow University of Health Sciences, Karachi, and
      involved 388 medical students who were voluntary participants. The 10-item
      Westside Test Anxiety Scale, was used to measure anxiety and the pre-designed
      questionnaire asked the students about the frequent measures used by them to
      overcome anxiety during exams and their past Grade Point Average. All data was
      coded and analysed using SPSS version 16 with a prior set alpha level of 0.05.
      RESULTS: Of the 450 students who were initially considered for the study, 388
      fulfilled the inclusion criteria. Among them, 101 (25.3%) were male students with
      a mean anxiety level of 2.55 +/- 1.27, and 287 (71.8%) were females with a mean
      anxiety level of 3.07 +/- 1.43 (p<0.05). Prayers and self-motivation (28.3%),
      sleep and relaxation (11%), television and music (10%), calling friends (8.5%)
      and revision (6.7%) were the frequent measures used by the medical students to
      overcome exam anxiety. Students in their fourth and final years of studies showed
      a higher level of anxiety compared to those in the 2nd and 3rd years. CONCLUSION:
      The study indicated high levels of exam anxiety among the medical students,
      showing that there is a need for anxiety-reduction programmes in medical
      colleges.

PMID- 23139996
TI  - Validation of the Urdu version of the Epworth Sleepiness Scale.
AB  - OBJECTIVE: To translate and validate the Epworth Sleepiness Scale (ESS) for use
      in Urdu-speaking population. METHODS: The original Epworth Sleepiness Scale was
      translated into the Urdu version (ESS-Ur) in three phases - translation and back
      translation; committee-based translation; and testing in bilingual individuals.
      The final was subsequently tested on 89 healthy bilingual subjects between
      February and April, 2010, to assess the validity of the translation compared to
      the original version. The subjects were students and employees of Dow University
      of Health Sciences, Karachi. RESULTS: Both English and Urdu versions of the
      Epworth Sleepiness Scale were administered to 59 (67%) women and 30 (33%) men.
      The mean composite Epworth score was 7.53 in English language and 7.7 in the Urdu
      version (p=0.76). The translated version was found to be highly correlated with
      the original scale (rho=0.938; p<.01). CONCLUSIONS: The study validated the
      scale's Urdu version as an effective tool for measuring daytime sleepiness in
      Urdu-speaking population. Future studies assessing the validity of such patients
      with sleep disorders need to be undertaken.

PMID- 23139997
TI  - Massive splenomegaly in acute erythroid leukaemia (FAB Class-M6): an unusual
      presentation.
AB  - AML-M6 has a peak incidence in the seventh decade with slight male preponderance,
      and can also present at a younger age. The usual features are anaemia,
      thrombocytopenia, malaise, fatigue, easy bruising, epistaxis and petechiae.
      Splenomegaly may occur in 20-40 % of the cases but massive splenomegaly is rare
      presentation and have been only reported once in humans and once in animals. A 22
      year Asian female, presented with fatigue, pallor, mild jaundice, exertional
      dyspnoea, epigastric pain, tender right hypochondrium and massive splenomegaly.
      Investigations revealed anaemia and thrombocytopenia, tear drop cells, basophilic
      stippling, piokilocytosis and anisochromia; increased uric acid and LDH.
      Abdominal ultrasound showed enlarged liver (22cm) and spleen (20cm). Bone marrow
      aspiration revealed 51% erythroid and 24% non-erythroid precursors, depressed
      leukopoeisis and megakarypoeisis. Erythroblasts were PAS and CD71 positive and
      also reacted to Antihaemoglobin-Antibody. This report highlights characteristic
      features and diagnostic criteria of erythroleukaemia, differential diagnosis of
      massive splenomegaly and their rare association.

PMID- 23139998
TI  - Developmental milestones: do the parents know enough?

PMID- 23139999
TI  - Rising trend of tattooing among young adults--a concern.

PMID- 23140000
TI  - HSE inspector advises on 'common mistakes'.
AB  - A recent IHEEM seminar on water hygiene and safety, 'The Invisible Threat', saw
      John Newbold, an HM specialist inspector at the Health and Safety Executive (HSE)
      with experience investigating Legionella cases and outbreaks, provide useful
      insight into how healthcare estates engineers and other 'responsible' personnel
      could ensure compliance with the law by properly 'managing and controlling'
      Legionella risk. He provided a first-hand view of what he dubbed 'some of the
      common mistakes' made by those responsible for managing water system safety, and
      gave useful advice and guidance on how to avoid them, and thus minimise the risk
      of falling foul of the HSE and other regulators. HEJ editor, Jonathan Baillie,
      reports.

PMID- 23140001
TI  - Legionnaires' disease--risk management.
AB  - Steve Mount, an independent Legionella management consultant and trainer with
      over 25 years' previous experience in microbiology and UKAS-accredited Legionella
      analysis, underlines the rising number of nosocomial cases of Legionnaires'
      disease in recent years, and explains the key risk assessment, management, and
      monitoring steps that must be taken by those responsible for hospital water
      systems to comply with legislation governing the 'control and management' of
      Legionella risk.

PMID- 23140002
TI  - Smaller, leaner estate--making it happen.
AB  - Conor Ellis, sector head, Health UK, at built asset consultancy, EC Harris,
      discusses how NHS Trusts in England can adopt an estates strategy that not only
      sees available space optimally matched with future clinical need, but equally, to
      secure maximum 'value' from their existing estate, sees under-utilised, ageing,
      or simply no longer serviceable buildings, sold, or developed for 'alternative
      use'. Where such a review has not been undertaken for at least three years,
      hesuggests conducting a 'six-facet' survey to establish the 'condition and
      suitability'of assets, 'as an effective tool for managing estate in an informed
      manner'.

PMID- 23140003
TI  - Getting window specification right.
AB  - Susan Duffy, a director of commercial glazing specialist, Fendor, draws on the
      company's many years' experience in supplying window solutions for applications
      ranging from schools to high secure mental healthcare facilities to provide
      useful guidance on specifying the optimal glazing solution, with a particular
      focus on what specifiers in the mental healthcare sector should be seeking in
      terms of design, glass type, strength, robustness, damage resistance, and anti
      ligature features. All too often, she cautions, a lack of sufficient technical
      guidance for estates teams faced with a myriad of responsibilities can see the
      'wrong' type of window selected, with potentially fatal consequencies.

PMID- 23140004
TI  - Maximising the value of existing buildings.
AB  - Graham McCorkindale, who heads the Health and Wellbeing strand at multi
      disciplinary architecture, town planning, interior design, and landscape
      architecture practice, Keppie Design, examines how architects can best support
      the NHS at a time of major change by refocusing design skills hitherto focused on
      creating new healthcare facilities on the need to work within the existing estate
      -'maximising utilisation and getting best value from any available spend'.

PMID- 23140005
TI  - Combining the best of the old and new.
AB  - Bristan claims to be the UK's largest supplier of bathroom and kitchen taps, and
      the second largest of mixer showers. With the launch, early in July 2011, as part
      of a major re-branding exercise, of 'a tailored collection' of taps, showers, and
      accessories, for commercial and public sector applications that brought together
      its own products with those from Sirrus by Gummers, the company is now targeting
      healthcare more seriously than ever before. Head of commercial specification,
      Richard Braid, told HEJ editor, Jonathan Baillie, that there are a number of
      exciting innovations already developed for healthcare specifiers, and several
      others 'in the pipeline'.

PMID- 23140006
TI  - Natural inspiration for valley hospital.
AB  - It is not often, according to HLM Architects, that that a hospital project is
      used as a catalyst for an area's social regeneration. As the practice itself puts
      it: 'Regeneration tends to rely on creating a sense of pride and local identity,
      qualities with which hospitals are rarely associated'. However creating a design
      that engendered a real sense of community ownership, and that local people could
      be really proud of, was precisely the challenge that faced the architects on the
      Ysbyty Cwm Cynon hospital project in South Wales, as HEJ reports.

PMID- 23140007
TI  - Copper shows its mettle worldwide.
AB  - While MRSA rates in England continue to fall, NHS Trusts are looking for smarter
      ways to achieve further reductions in infection rates, or to support their 'zero
      tolerance approaches', and, according to the Copper Development Association
      (CDA), the not-for-profit, membership-based organisation which supports and
      promotes 'the correct and efficient use of copper and its alloys', deployment of
      antimicrobial copper touch surfaces is being adopted in many hospitals and other
      healthcare facilities worldwide as 'an additional and cost-effective infection
      control measure'. CDA Director Angela Vessey highlights the benefits, and
      examines some of the growing number of healthcare installations of 'antimicrobial
      copper' worldwide.

PMID- 23140008
TI  - How to keep on top of roofing issues.
AB  - Paul Franklin, who heads up the Technical team at Bedford-based specialist
      testing and defect analysis company, RAM Consultancy, explains how healthcare
      building owners and occupiers such as NHS Trusts, and their estates and
      facilities teams, can best manage, maintain, and, when necessary, refurbish,
      their building envelope and roofs, in the process gaining some perhaps unexpected
      benefits.

PMID- 23140009
TI  - Projects with an eye to the future.
AB  - In recent years, London's Imperial College Healthcare NHS Trust has undertaken a
      number of ward refurbishments aimed at meeting the future requirements of the
      hospital head on. In the most recent projects, at St Mary's Hospital in
      Paddington, and at the Western Eye Hospital in the Marylebone Road, the Trust
      harnessed the construction expertise and experience of main contractor Longcross,
      selecting the company for its 'proven track record in delivering schemes in live
      working environments on time, on budget, and to a high standard, while causing
      minimal disruption'. HEJ reports.

PMID- 23140010
TI  - Emergency lighting gets 'smarter'.
AB  - Alan Daniels, business development director of emergency lighting specialist, P4,
      describes the latest trends in, and requirements for, emergency lighting, a vital
      part of the building services footprint in hospitals and other healthcare
      premises. He also explains how those responsible for the safe operation of
      emergency lighting system can ensure they comply with their obligations under the
      law.

PMID- 23140011
TI  - Move signals the 'start of new era'.
AB  - Thirty-one years after its establishment in a small office in Wigan, independent
      life safety equipment manufacturer, C-TEC, has moved into a new 75,000 ft2
      factory, 'the size of three football pitches', marking the start of what founder
      and MD, Andrew Foster, dubs 'the next phase in our exciting development'. The
      past year has also seen the firm busy on the new product front, with the launch
      of a 'revolutionary' new range of touchscreen-controlled analogue addressable
      fire alarms panels which the company claims will put it 'way ahead of the
      competition', and, in response to demand from nursing and care home operator
      customers, the introduction of a range of components designed to facilitate
      dementia care as an extension to its well-established Quantec addressable call
      system. HEJ editor, Jonathan Baillie, reports.

PMID- 23140012
TI  - Drainage: 'prevention is better than cure'.
AB  - Excellent standards of cleanliness are more important for healthcare facilities
      than in virtually every other type of building, and well-managed drainage systems
      play a crucial part in this. business and commercial, utilities, public sector,
      and facilities management clients. Nick Reilly, director at UKDN Waterflow,
      discusses best practice in this area for healthcare estates managers.

PMID- 23140013
TI  - Rapid expansion to cut waiting times.
AB  - Robert Snook, director and general manager of Portakabin Hire, offers some
      practical advice to, as he puts it, 'help healthcare providers rapidly expand
      hospital facilities to reduce patient waiting times with no compromise on the
      quality of the accommodation'. He argues that hired modular buildings can offer a
      considerably faster solution than traditionally built structures where additional
      capacity is needed urgently to meet added demand, or, for instance, during major
      refurbishment or upgrading of existing facilities.

PMID- 23140014
TI  - Conceived to have a community feel.
AB  - Last month over 100 service users moved into a new purpose-designed and built
      modern mental healthcare centre, The Redwoods Centre, near the 'old' Shelton
      Hospital on the outskirts of Shrewsbury, a new 46 million sterling pounds
      facility for adults with acute mental healthcare needs and organic (brain
      impairment) mental health conditions. It has been designed and built under
      ProCure21 by BAM Construction. HEJ editor, Jonathan Baillie, visited the new
      facility, plans for which were first mooted in 1956, to discover from project
      director, Andrew Hughes, why it was so badly needed, and discuss its design and
      construction with BAM Construction's construction manager, Dave Ellis. An
      architectural standpoint is provided by project associate at Nightingale
      Associates, Anthony Keats.

PMID- 23140015
TI  - Iranian children inform renovation project.
AB  - Dr Sanaz Litkouhi, assistant professor and director of the Architecture and Urban
      Planning Department at the Payame Noor University, in Tehran, the author of a
      number of previous articles for HEJ on optimal design of healthcare facilities
      for children and adolescents (HEJ - November 2007, March 2008, and May 2010),
      describes how service users' views were carefully gauged and taken into
      consideration in a project involving renovation of part of the Shahid Bahrami
      Children's Hospital in Tehran.

PMID- 23140016
TI  - Regulation of telomerase activity in ovarian granulosa cells.
AB  - Follicular development is characterized by intensive proliferation and
      differentiation of granulosa cells. It was reported that during follicular growth
      granulosa cells arise from the population of stem cells. One of the main
      evidences for stem characteristics of the cell is the ability to express
      telomerase--an enzyme complex responsible for integrity and stability of
      chromosome ends (telomeres). It was demonstrated that telomerase activity in
      granulosa cells is linked to their proliferation and differentiation status and
      is under the control of growth factors and steroid hormones. In this review
      current knowledge on the existence and regulation of telomerase activity in
      granulosa cells has been presented.

PMID- 23140017
TI  - Effect of methanolic and water extract of Leucobryum bowringii Mitt. on growth,
      migration and invasion of MCF 7 human breast cancer cells in vitro.
AB  - Inhibitory effects of methanol and water extract of L. bowringii. on the
      adhesion, migration, invasion and matrix metalloproteinase (MMP) activities of
      MCF 7 human breast cancer cell line are reported. Cells were cultured with 10,
      25, 50 microg/mL methanolic or water extract of L. bowringii. Culture medium
      containing 0.1% DMSO was used as a solvent control. Ultra structural analysis by
      electron microscopy revealed typical features of apoptosis. A remarkable dose
      response parallelism was observed between methanolic extract with growth,
      migration and invasion of breast cancer cells. Fractionation of methanolic
      extract by RP-HPLC revealed a pool of phenolic acids. Hoechst 33342 staining
      assay reveals massive chromatin condensation and subsequent cleavage of
      structural components of nucleus. The results indicate that methanol extracts
      inhibit the growth of human breast cancer cells partially through the inhibition
      of metallo proteinases MMP-2 and MMP-9 activities. Methanolic extract has more
      anti-metastatic effects in cell based assay than water extract. Clinical
      application of L. bowringii extract as a bioactive chemopreventive compound may
      be helpful in limiting breast carcinoma invasion and metastasis.

PMID- 23140018
TI  - Polysaccharide enriched immunomodulatory fractions from Tinospora cordifolia
      (Willd) miers ax hook. f. & Thoms.
AB  - Tinospora cordifolia is used in Ayurveda as "Rasayanas" to improve the immune
      system and the body resistance against infections. Polysaccharides are the main
      constituents which are considered to be responsible for immune enhancement. In
      this study, immunomodulatory activity of three polysaccharide enriched fractions
      was evaluated using the polymorphonuclear leukocyte function test. Sugar
      composition was determined by GC-MS analysis of the derivatised fractions. The
      active polysaccharide fractions mainly constitute glucose, fructose and arabinose
      as monomer units.

PMID- 23140019
TI  - In vitro expression studies of non structural 1 protein of Canine Parvo virus 2
      by polyclonal antiserum raised against CPV2-NS1 protein expressed in Escherichia
      coli as an antigen.
AB  - The canine Parvovirus 2, non-structural 1 (NS1) is a novel candidate tumor
      suppressor gene. To confirm the expression of the NS1 in HeLa cells after
      transfection there was a need to raise antiserum against CPV2- NS1. Therefore,
      this study was carried out to express and purify the recombinant NS1 (rNS1), and
      characterize the polyclonal serum. CPV2-NS1, complete coding sequence (CDS) was
      amplified, cloned in pET32a+ and expressed in BL21 (DE3) (pLysS). SDS-PAGE
      analysis revealed that the expression of the recombinant protein was maximum when
      induced with 1.5 mM IPTG. The 6 x His tagged fusion protein was purified on Ni
      NTA resin under denaturing conditions and confirmed by western blot using CPV2
      specific antiserum. The rabbits were immunized with the purified rNS1 to raise
      anti-NS1 polyclonal antiserum. The polyclonal serum was tested for specificity
      and used for confirming the expression of NS1 in HeLa transfected with
      pcDNA.cpv2.ns1 by indirect fluorescent antibody test (IFAT), flow cytometry and
      western blot. The polyclonal antiserum against NS1 could be very useful to
      establish functional in vitro assays to explore role of NS1 in cancer
      therapeutics.

PMID- 23140020
TI  - Antidepressant and anxiolytic-like effects of 4n, a novel 5-HT3 receptor
      antagonist using behaviour based rodent models.
AB  - The present study was designed to investigate the putative antidepressant and
      anxiolytic-like effects of N-n-Butylquinoxalin-2-carboxamide (4n), a novel 5-HT3
      receptor antagonist, with an optimal log P (2.01) and pA2 value (7.3) greater
      than ondansetron (6.9) using rodent behavioural models of depression and anxiety.
      Acute treatment of 4n (1-4 mg/kg, ip) in mice produced antidepressant-like effect
      in forced swim test (FST) without affecting the baseline locomotion in
      actophotometer test in mice. 4n (2-4 mg/kg, ip) treatment also potentiated the 5
      hydroxytryptophan (5-HTP) induced head twitch response in mice. Further, 4n (1-4
      mg/kg, ip) treatment antagonized reserpine induced hypothermia in rats. Chronic
      treatment (14 days) with 4n (1-4 mg/kg) and paroxetine (10 mg/kg) significantly
      attenuated the behavioural anomalies induced by bilateral olfactory bulbectomy in
      rats in modified open field paradigm. An anxiogenic-like behaviour was induced by
      light alone as the stimulus using light-dark aversion test. 4n (2-4 mg/kg, ip)
      treatment significantly increased no. of transitions between dark and lit area
      and the time spent in the lit area. In conclusion, these preliminary
      investigations confirm that 4n exhibited antidepressant and anxiolytic-like
      effects in rodent models of depression and anxiety.

PMID- 23140021
TI  - Role of C-fibers during acute and chronic stress on formalin-induced paw edema in
      rats.
AB  - Stimulation of peripheral nociceptors leads to releasing of some mediators such
      as substance P (SP) and Calcitonin gene-related peptide (CGRP) and contributes to
      the edema formation by vasodilatation induction. On the other hand
      glucocorticoids have anti-inflammatory action, and they are elevated in the
      plasma during stress. This communication reports C-fibers inflammatory role and
      the effects of chronic and acute stress and/or dexamethasone (as stress mimicry)
      on paw edema induced by formalin at presence/deficit C-fibers rats. Acute stress
      and dexamethasone and chronic dexamethasone have shown an anti-inflammatory
      effect in C-normal groups, but chronic stress had no effect on inflammation. C
      fibers reduction (C-lesion) had anti-inflammatory effects. In deficit C-fibers
      rats, acute and chronic stress had not stronger anti-inflammatory effect, but
      acute dexamethasone reduced the anti-inflammatory effect of C-fibers reduction
      while in the same condition, chronic dexamethasone induced stronger anti
      inflammatory effect. The results show C-fiber nerve produce and release the
      peripheral inflammatory mediators, "C-fibers reduction" decreased the paw
      inflammation. Counter adaptation in C-lesion animals may reduce the modulatory
      effects of dexamethasone on the remaining C-fibers. Acute dexamethasone
      diminished the "C-fibers reduction" anti-inflammatory effect, but at chronic
      treatment, the modulatory effects of dexamethasone aggregated and it augmented
      the C-fibers reduction antiinflammatory effect.

PMID- 23140022
TI  - Protective effects of subchronic caffeine administration on cisplatin induced
      urogenital toxicity in male mice.
AB  - In Cisplatin treated group, the degeneration intensity of the kidneys the
      diameter of seminiferous tubules as well as the apoptotic index in testes and
      kidney were increased. In Caffeine+Cisplatin treated groups, the total body
      weight, the weight of testes and kidneys and also the histopathological data did
      not show significant differences. The motility of sperm in cisplatin group
      reduced but in Caffeine+Cisplatin groups this parameter was increased. These data
      suggest that caffeine recovers toxicity induced by cisplatin in both kidneys and
      testes of mice.

PMID- 23140023
TI  - Thirteen-week oral toxicity study of carotenoid pigment from Rhodotorula glutinis
      DFR-PDY in rats.
AB  - Carotenoids from some of the coloured yeasts like Rhodotorula, Phaffia rhodozyma
      have attracted commercial interest as a natural pigment for foods. Red yeast
      isolated from contaminated Potato dextrose agar plate (PDA), designated as
      Rhodotorula glutinis DFR-PDY has been found to produce carotenoids. In the
      present study toxicological evaluation of carotenoid pigment has been reported.
      Experiment was conducted on 3 groups of albino rats. One group with vehicle
      control (palm oil) and 2 groups with two different doses of red yeast pigment
      (lower and higher dose) were fed to rats (both male and female) by gavages for 13
      weeks. Gain in body weight of rats and food consumption were monitored at regular
      intervals. Hematological studies revealed that there is no much difference in
      erythrocytes, packed cell volume, Mean corpuscular volume (MCV), Mean corpuscular
      haemoglobin concentration (MCHC), platelets and differential counts. Total
      leucocyte count (TLC) is less in case of higher dose group than the lower and
      control groups. Whereas, hemoglobin is more in case of higher dose than the lower
      dose group and least in control group. Even clinico-chemical parameters and urine
      analysis of vehicle control group and pigment fed rats revealed that there were
      no major differences between them as well as between two different genders of
      rats and also interaction between different doses and the genders. Histopathology
      of these experimental animals revealed that there are no major histological
      changes found between the groups. It may be concluded that the whole pigment
      extract from R. glutinis DFR-PDY may be used safely in food preparations as food
      colourant with an added benefit of antioxidant activity.

PMID- 23140024
TI  - Functional ureogenesis and changes of amino acid metabolism in amphihaline shad
      hilsa (Tenualosa ilisha, Hamilton-Buchanan) while inhabiting in estuary and
      freshwater habitats.
AB  - The possible occurrence of a functional ornithine-urea cycle (OUC) and changes of
      activity of key amino acid metabolism-related enzymes were studied in the
      amphihaline shad hilsa (Tenualosa ilisha) that were collected from estuarine
      water of Kakdwip and from freshwater river basin of Bhrahmaputra during the
      breeding season. Very high concentration of urea was detected in different
      tissues and plasma of shad hilsa collected from estuarine water compared to the
      one collected from freshwater river basin. This observation clearly suggests that
      the shad hilsa has the potential of synthesizing and retaining urea inside the
      body for the purpose of osmoregulation while living in hypertonic saline
      environment of estuary. This was accompanied by the presence of high activity of
      all the five OUC enzymes in hepatic and in certain non-hepatic tissues such as
      the kidney and muscle of shad hilsa in support of its potential ureogenic
      capacity while inhabiting in estuarine water. The activities of different key
      amino acid metabolism-related enzymes such as glutamine synthetase, glutamate
      dehydrogenase, alanine aminotransaminase and aspartate aminotransaminase were
      also found to be significantly higher in shad hilsa of estuarine water compared
      to the one collected from freshwater habitat. Thus the adjustment to amino acid
      metabolism in shad hilsa in different environmental salinities appears to play
      significant roles for osmotic balance and also for proper energy supply in
      addition to the presence of a functional OUC while migrating between marine and
      freshwater habitats throughout their life cycle.

PMID- 23140025
TI  - Eclosion behaviour of three species of Drosophila under different light regimes.
AB  - The daily patterning of animal behaviour is presumed to be due to changes in
      responsiveness to external stimuli, as a function of varying internal states
      which may be oscillating with a 24 h period. The endogenous circadian system
      functions to organize behaviour and physiology to adapt to and anticipate
      environmental changes in light, temperature, food and mate availability. Light is
      most important zeitgeber that influence circadian physiology of several insects.
      The present study is an attempt to understand the eclosion behaviour of
      Drosophila melanogaster (Oregon-K strain), Drosophila gangotrii and Drosophila
      jambulina under light/dark (LD), continuous light (LL), continuous dark (DD)
      conditions for 30 generations. The stocks were maintained at 20 +/- 1 degrees C
      with 75% RH. Eclosion behaviour was analyzed at 4 h intervals until complete
      emergence of flies. Result reveals that in all the species peak of eclosion was
      found at dawn and on subjective day. Intraspecies comparison shows that there was
      no significant difference in eclosion at different time point and generations
      under different light regimes. However, interspecies comparison shows significant
      difference for hours. The data from experiments showed altered rhythm in the form
      of phase advance and phase delay in eclosion at different light regimes
      suggesting the role of photoperiod in the physiology of organisms.

PMID- 23140026
TI  - Dysmenorrhea in Siriraj medical students; prevalence, quality of life, and
      knowledge of management.
AB  - OBJECTIVE: To determine the prevalence of dysmenorrhea, effect on daily activity,
      academic activities, quality of life, and knowledge of management in Siriraj
      medical students. MATERIAL AND METHOD: A cross-sectional descriptive study at the
      Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand that
      included 552 female medical students who were asked to complete two
      questionnaires. The first questionnaire (32 items) included demographic data,
      menstrual pattern, severity of dysmenorrhea, pain score, impact of dysmenorrhea
      on daily and academic activities, the method and knowledge of medications to
      treat dysmenorrhea. The second questionnaire was Short Form (SF)-36
      questionnaires used to evaluate the health-related quality of life. RESULTS: The
      prevalence of dysmenorrhea was 77.7%. The prevalence of mild, moderate, and
      severe dysmenorrhea was 35.3%, 39.3%, and 3.1% respectively. Age of menarche,
      duration of menses, and the family history of dysmenorrhea were significantly
      different between two groups. Students who had moderate to severe dysmenorrhea
      reported the negative impact on daily and academic activities. The scores of SF
      36 in moderate and severe group was significantly lower than the mild group (p <
      0.001). In the moderate to severe dysmenorrhea group, 82.9% and 66.7% of
      participants used mefenamic acid and paracetamol for pain relief respectively.
      CONCLUSION: Dysmenorrhea in medical students has high prevalence and it has
      negative effects on daily activities, academic activities, and quality of life.
      Most of the subjects know that mefenamic acid and/or paracetamol can relief
      dysmenorrhea. Dysmenorrhea is a significant public health problem.

PMID- 23140027
TI  - Normogram of fetal middle cerebral artery peak systolic velocity at 20-37 weeks
      of gestation at Srinagarind Hospital.
AB  - OBJECTIVE: To establish normal references of fetal middle cerebral artery peak
      systolic velocity (MCA PSV) at 20 to 37 weeks of gestation at Srinagarind
      Hospital. MATERIAL AND METHOD: A descriptive cross-sectional study was performed
      Normal fetuses at 20 to 37 weeks of gestation were studied by gray scale
      ultrasonography initially and then Doppler of MCA PSV. RESULTS: At least 18
      pregnant women of each gestational age with an uncomplicated singleton were
      enrolled The MCA PSV was increased as gestational age advanced from 24.34 cm/sec
      (SD 3.91) at 20 weeks to 59.04 cm/sec (SD 10.80) at 37 weeks. CONCLUSION: A
      normogram of fetal MCA PSV at 20 to 37 weeks of gestation at Srinagarind hospital
      was generated.

PMID- 23140028
TI  - Obstetric care and health system responsiveness for hospital-based delivery in
      Lao People's Democratic Republic.
AB  - OBJECTIVE: To assess obstetric care and health system responsiveness for hospital
      based delivery care in Lao PDR, and associated factors. MATERIAL AND METHOD: A
      cross-sectional study was conducted in two provincial hospitals in Lao PDR
      between June and October 2010. All delivered women were interviewed for their
      perception of health system responsiveness and their medical records were
      reviewed for the obstetric care they received. RESULTS: Five hundred eighty one
      women participated in this study. The mean scores of obstetric care and health
      system responsiveness were 19.5 +/- 2.5 and 31.6 +/- 1.5, respectively. The mean
      score of overall performance was 51.0 +/- 2.8. Of the two hospitals, designated
      as Hospital A and Hospital B, the health responsiveness was rated lower in women
      undergoing cesarean section and delivering in Hospital B. Male doctor or
      obstetrician or delivery in Hospital B was significantly associated with higher
      obstetric care and overall performance. CONCLUSION: Different health system
      responsiveness for the delivery care between the two hospitals was found.
      Strategies to improve obstetric care need to be discussed and studied.

PMID- 23140029
TI  - Prevalence of endometriosis among patients with adenomyosis and/or myoma uteri
      scheduled for a hysterectomy.
AB  - OBJECTIVE: To estimate the prevalence of endometriosis among patients between 40
      and 50-years-old that required a hysterectomy with an indication of adenomyosis
      and/or myoma uteri. MATERIAL AND METHOD: This cross-sectional study was conducted
      in a university hospital. Two hundred twenty consecutive premenopausal women,
      aged 40 to 50-years-old, with symptomatic adenomyosis and/or myoma uteri, and
      scheduled for a total abdominal hysterectomy were enrolled. During laparotomy, a
      systematic inspection of the pelvis was carried out to identify endometriosis.
      RESULTS: The presence of endometriosis was observed in 63 (28.6%) of 220
      patients. The prevalence of endometriosis was 19 in 47 (40.4%) patients with
      adenomyosis, 30 in 132 (22.7%) patients with leiomyomas, and 14 in 41 (34.1%)
      patients with adenomyosis and leiomyomas. The rate of coexistence of
      endometriosis in the women with adenomyosis was statistically significantly
      higher than in the patients with leiomyomas (p-value = 0.032). Younger age,
      moderate-severe pain, and short menstrual interval were shown to be independent
      risk factors for endometriosis among these patients. CONCLUSION: The prevalence
      of endometriosis in the women with adenomyosis was higher than in those with
      leiomyomas.

PMID- 23140030
TI  - Prognostic factors and survival of borderline ovarian tumors in Rajavithi
      Hospital between 1979-2006 A.D.
AB  - OBJECTIVE: Evaluate 5-year progression-free survival, 5-year disease-specific
      survival, and prognostic factors for recurrence and survival in patients with
      borderline ovarian tumors in Rajavithi Hospital. MATERIAL AND METHOD: A
      retrospective study of the patients with borderline ovarian tumors who were
      treated at Rajavithi Hospital before 2006 was performed Patients 'clinical
      characteristics, detail of treatment and all variables that seemed to influence
      survival or recurrence of disease and patients' life status were obtained from
      gynecologic oncologic files, medical record documents, and National Population
      Statistic Office Database RESULTS: Two hundred ten patients were enrolled in the
      present study. Nearly 90% (187 patients, 89%) had stage I disease. Another seven
      (3.3%) were in stage II, 15 (7.2%) in stage III, and one (0.5%) in stage IV. The
      most common histology was mucinous (157 patients, 74.8%), followed by serous (49
      patients, 23.3%) and mixed serous and mucinous (4 patients, 1.9%). The mean age
      of the patients was 41 years (range, 14 to 82 years). The mean size of tumor was
      17 cm (range, 5 to 40 cm). The majority of primary treatment was by surgery only
      at approximately 87.6% (184 patients) and the remaining 12.4% (26 patients) was
      surgery plus adjuvant chemotherapy. Bilateral ovarian involvement was found in 13
      patients (6.2%). Twenty-three percent of patients with peritoneal implants had
      bilateral ovarian involvement whereas the rate in the group without peritoneal
      implants was 5.7%. The 5-year progression-free survival (PFS) and 5-year disease
      specific interval (DSS) were 92.32% and 95.72% respectively. Nine patients (4.3%)
      had recurrence of disease and 11 (5.2%) died of disease. Salvage therapy mainly
      was surgery and three patients (33%) were cured without evidence of disease.
      Univariate analysis showed two significant prognostic factors for PFS. Those were
      stage of disease and optimal debulking. The four significant prognostic factors
      for DSS were stage of disease, optimal debulking, rupture of tumor and presence
      of ascites. Conservative surgery, incomplete staging, lymphadenectomy,
      periovarian adhesion, or positive peritoneal cytology did not seem to influence
      PFS and DSS. Independent prognostic factor for PFS and DSS could not be
      conclusively drawn by multivariate analysis because of far too few death and
      recurrence events in the present study. CONCLUSION: The borderline ovarian tumors
      had an excellent prognosis. Conservative surgery should be carried out in women
      at reproductive age with early stage of disease who have fertility desire.

PMID- 23140031
TI  - Rectal balloon training as an adjunctive method for pelvic floor muscle training
      in conservative management of stress urinary incontinence: a pilot study.
AB  - BACKGROUND: Pelvic floor muscle training (PFMT) is currently considered as the
      first line conservative management for women with stress urinary incontinence
      (SUI). However, it is difficult for some women to self-identify the contraction
      of the pelvic floor muscle after they were trained by verbal instruction. Various
      techniques including rectal balloon probe have been developed to improve PFMT.
      OBJECTIVE: To compare vaginal squeezing pressure, one-hour pad test, leakage
      episodes, rating scores about severity of SUI, and patient satisfaction between
      traditional PFMT and rectal balloon training (RBT). MATERIAL AND METHOD: Twenty
      eight patients with SUI were randomized into two groups, PFMT, and RBT groups.
      The PFMT group was verbally instructed to perform exercise as the traditional
      technique. In the RBT group, a Foley catheter filled with tap water to create
      balloon was inserted into the rectum in combination with the same exercise as in
      the PFMT group. The vaginal squeezing pressure before and after 6-week exercise
      program was measured by biofeedback machine model MYO420. RESULTS: One patient in
      each group was lost to follow-up. This left 13 patients in each group. Both
      groups had statistically significant gained in vaginal squeezing pressure after
      exercise. The different pressure between pre and post exercise were 9.9 mmHg and
      9.2 mmHg in PFMT and RBT group respectively (p = 0.84). Significant improvement
      of leakage episodes and self-rating scores assessed the severity of SUI after
      exercise was reported in both groups, although there was no significant
      difference between both groups. The number of patients wearing protection after
      exercise was lowered in both groups, which were 75% in PFMT group and 80% in RBT
      group. However satisfaction was greater after completing exercise in both groups.
      CONCLUSION: PFMT is an effective conservative treatment of SUI. PFMT combined
      with rectal balloon training did not provide greater strength of the pelvic floor
      muscle than isometric contraction.

PMID- 23140032
TI  - Appropriate body mass index and waist circumference cutoffs for middle and older
      age group in Thailand: data of 19,621 participants from Thai epidemiologic stroke
      (TES) study.
AB  - OBJECTIVE: To determine the appropriate body mass index (BMI) and waist
      circumference (WC) cutoff point for identification of at least one cardiovascular
      risk factor (hypertension, dyslipidemia, and type 2 diabetes) in Thailand, and to
      compare the discrimination ability of BMI with that of WC for discrimination of
      at least one cardiovascular risk factor. MATERIAL AND METHOD: Baseline health
      survey data of participants of Thai Epidemiologic Stroke (TES) Study, who were
      free from stroke, enrolled from five geographic regions around the country, were
      studied as cross-sectional analysis. Receiver operating characteristics curve
      (ROC) analysis was performed to determine the appropriate cutoff points of BMI
      and WC in identifying those with presence of at least one cardiovascular risk
      factors. The BMI or WC value with the shortest distance on the ROC curve was
      considered to be appropriate cutoffs. Comparing the ability of BMI in
      discrimination of at least one cardiovascular risk factor with that of WC was
      performed by comparing ROC area under curve (AUC). RESULTS: Among 19,621 (6,608
      men and 13,013 women) participants with age range of 45 to 80 years, the average
      age was 59.8 years for men and 58.5 years for women. The appropriate cutoff point
      of BMI was 23 kg/m2 in men and 24 kg/m2 in women. The cutoffs of WC were 80 cm
      and 78 cm in men and women, respectively. In both gender, waist circumference
      (WC) (AUC in men = 0.684; 95% CI, 0.672-0.695, AUC in women = 0.673; 95% CI,
      0.665-0.681) was significantly (p < 0.001) better than BMI (AUC in men = 0.667;
      95% CI, 0.656-0.679, AUC in women = 0.636; 95% CI, 0.628-0.644) in discrimination
      of at least one cardiovascular risk factor. CONCLUSION: In Thai adults aged 45 to
      80 years, the cutoff points of BMI should be 23 kg/m2 in men and 24 kg/m2 in
      women. For WC, 80 cm and 78 cm should be considered to be appropriate cutoffs for
      men and women, respectively. Waist circumference (WC) as a simple obesity index
      should be advocated for public health screening.

PMID- 23140033
TI  - Incidence and risk factors of perioperative stroke in Siriraj Hospital.
AB  - BACKGROUND: Data concerning perioperative stroke incidence and risk factors are
      lacking in Thailand. OBJECTIVE: To study incidence and risk factors of
      perioperative stroke in Siriraj Hospital, Bangkok, Thailand. MATERIAL AND METHOD:
      The authors conducted a nested case-control study between July 2007 and June
      2010. Consecutive perioperative stroke cases were compared with age-matched
      controls that had undergone surgery without having a stroke at a 1:4 ratio.
      Patients' characteristics, co-morbidities, clinical manifestation, stroke
      subtypes, duration, and types of surgery were collected. Multiple logistic
      regression analysis was performed to identify factors associated with a stroke
      during perioperative period. RESULTS: Sixty-six patients with perioperative
      stroke from 99,283 that underwent surgery were included. This resulted in an
      incidence of 66.5/100,000. Men comprised 65.2%. Mean age of stroke patients was
      66.6-years-old. Age-match controls included 264 consecutive patients who
      underwent surgery without having a stroke. A multivariate analysis showed that
      male sex (adjusted OR 3.1, p = 0.003), surgical types: open heart surgery
      (adjusted OR 54.3, p < 0.0001), vascular surgery (adjusted OR 20.6, p < 0.0001)
      and endovascular procedure (adjusted OR 15.4, p < 0.0001), emergency surgery
      (adjusted OR 8.3, p < 0.0001), the presence of diabetes mellitus (adjusted OR
      2.6, p = 0.018), chronic kidney disease (adjusted OR 2.6, p = 0.027), and
      coronary artery disease (adjusted OR 0.4, p = 0.039) were associated with
      perioperative stroke. CONCLUSION: Incidence of perioperative stroke was higher
      than a previous report. Male, type of surgery, emergency operation, diabetes
      mellitus, and chronic kidney disease were risk factors of perioperative stroke.

PMID- 23140034
TI  - Outcomes after temporal lobectomy for temporal lobe epilepsy with hippocampal
      sclerosis.
AB  - OBJECTIVE: Outcome predictors from the pure cohorts of patients with temporal
      lobe epilepsy (TLE) with hippocampal sclerosis (HS) are limited The aim of the
      present study was to assess seizure outcomes and predictive factors in groups of
      well-defined patients with TLE-HS. MATERIAL AND METHOD: One hundred forty eight
      patients with drug resistant TLE who had magnetic resonance imaging (MRI) that
      demonstrated unilateral HS underwent temporal lobectomy between 2004 and 2008 by
      a single neurosurgeon. All patients had completed at least two years of follow
      up. Seizure outcome was categorized into seizure-free and not seizure-free.
      RESULTS: Ninety-five patients (64.2%) were seizure-free after surgery at two
      years of follow-up. At four years follow-up, 47 patients (77.1%) were seizure
      free for at least two years. There was no operative mortality or significant
      morbidity. No clinical variables are predictive of surgical outcomes at two and
      four years offollow-up. CONCLUSION: Temporal lobectomy for drug-resistant TLE
      with HS is safe and effective. The authors did not identify predictive factors of
      surgical outcomes in TLE-HS.

PMID- 23140035
TI  - Validation of EuroSCORE for coronary artery bypass grafting at Siriraj Hospital.
AB  - OBJECTIVE: To access the performance of the EuroSCORE when applied to CABG
      patients at Siriraj hospital. MATERIAL AND METHOD: One thousand five hundred
      forty nine patients diagnosed with coronary artery disease (CAD) who underwent
      isolated CABG between January 2007 and December 2009 was prospectively studied.
      RESULTS: The patients included 1,102 men and 447 women and had a mean age of 67
      years old. The mean additive score in expired and survived groups were 9.65 +/-
      5.14 and 3.87 +/- 3.06. In logistic, score were 25.43 +/- 26.31 and 4.88 +/- 7.88
      respectively (p < 0.001). The best cut-off value of EuroSCORE for prediction of a
      death rate was 6 for additive score and 10 for logistic score. Area under the
      curve was 0.831 for the additive score and 0.823 for the logistic score. The
      observed overall mortality rate was 2.0% while the predict mortality was 5.27%.
      The difference between observed and predicted deaths was significant with
      additive score and logistic score (p < 0.001). CONCLUSION: Our results suggest
      that EuroSCORE is not valid for CABG in Thai patient due to over prediction.

PMID- 23140036
TI  - A one-year prospective follow-up study of a DIR/Floortime parent training
      intervention for pre-school children with autistic spectrum disorders.
AB  - OBJECTIVE: Determine the results of 1-year Developmental, Individual-Difference,
      Relationship-Based (DIR)/Floortime parent training in developmental stimulation
      of children with autistic spectrum disorder (ASD). MATERIAL AND METHOD: Thirty
      four, two to six years old children with ASD participated. Parents were
      encouraged to deliver 1:1 interaction according to their child's developmental
      level, as they were modeled and coached. Pre-post videotapes were rated by
      blinded assessors. RESULTS: Thirty-one families completed the present study. The
      data showed that adding home-base DIR/Floortime intervention at the average 14.2
      hours/week for one year could help 47% of the children to make good improvement
      (1.5 Functional Development Level, FDLs or more), with 23% making fair
      progression (1 FDL), and the last 29% making poor progression (0.5 FDL or less).
      There were significant increases in children's total Functional Emotional
      Assessment Scale (FEAS), and Functional Emotional Developmental Questionnaire
      (FEDQ) scores and there was significant decrease in the Childhood Autism Rating
      Scale (CARS) scores (p < or = 0.001). It showed that fidelity of the parents,
      severity of the children, and baseline developmental status might affect the
      outcome. CONCLUSION: Adding home-base DIR/Floortime intervention at the average
      14 hours/week for one year helped 47% of children with autism to make good
      improvement in their development, and decreased autism's severity significantly.

PMID- 23140037
TI  - Accuracy of three methods used for Thai children's body weight estimation.
AB  - BACKGROUND: Accurate children's weight estimation is necessary and important for
      emergency pediatric care, particularly for drug dosages, electrical therapy, or
      equipment sizes. Children's weight is difficult to measure in critically ill
      patients. Several methods were developed to estimate children's accurate weight.
      Most methods were developed from western countries. The methods used currently
      might not work with Thai children. OBJECTIVE: To determine the accuracy of the
      Broselow tape, family member estimation and the 50th percentile of national
      weight for height correlation graph for Thai children's weight estimation.
      MATERIAL AND METHOD: The authors carried out a prospective study. Children from
      neonate to 12 years old who presented to the emergency department and general
      outpatient pediatric clinic were included. The patients were studied in both
      overall and subgroup analysis (less than 10 kg, 10 to 25 kg, 25 to 40 kg, and
      over 40 kg). The primary outcome was the accuracy within 10% error of the
      measured weight and the mean difference of the weight. RESULTS: Five hundred
      ninety five patients were included in the present study. There were 333 (55.97%)
      boys and 262 (44.03%) girls. Family member estimation was the most accurate
      method with the accuracy within 10% error 85.21% and had the lowest mean
      difference (-0.262 kg). Family members could estimate weight accurately for all
      weight subgroups. The Broselow tape was the second most accurate method with the
      accuracy within 10% error 56.13% and the low mean difference (-0.485 kg). The
      accuracy within 10% error of the 50th percentile of national weight for height
      correlation graph was 51.43% and the mean difference was -0.648 kg. Every method
      had the best estimation in the weight subgroup 10 to 25 kg except the Broselow
      tape. CONCLUSION: Family member estimation was the most accurate method in the
      present study. The family member could estimate the children's weight within 10%
      error of the measured weight about 85% of cases. In case where family member
      estimation was not available, the Broselow tape was the next accurate alternative
      method.

PMID- 23140038
TI  - Clinical outcomes of cervical node metastasis from an unknown primary in
      Songklanagarind Hospital.
AB  - OBJECTIVE: To study the clinical outcomes of cervical lymph node metastases from
      an unknown primary site. MATERIAL AND METHOD: A retrospective review of 139
      patients diagnosed with cervical neck node metastases from an unknown primary
      site in Songklanagarind Hospital between 2000 and 2010 was included. The data of
      patient and tumor characteristics, diagnostic procedures, and treatment outcomes
      were recorded. The disease-free and overall survival rates were calculated
      RESULTS: Age ranged from 33 to 95 years with male predominance in 121 patients
      (87%). The majority of histological finding was squamous cell carcinoma and
      poorly differentiated grading was predominant. The 3- and 5-year disease
      free/overall survival rates were 55.5/33.9% and 48.6/27.8%, respectively. The
      survival rate was lower significantly in level IV, N3 stage, extracapsular
      spread, and distant metastasis. The surgery followed by radiation seemed to
      improve the overall survival of 32.6% at five years. By the average follow-up
      time of 29.8 months, the emerging primary tumor was found in 12 patients (8.6%).
      CONCLUSION: The important prognostic factors are nodal status, metastasis, and
      extracapsular extension. Panendoscopy is recommended for routine diagnostic work
      up, as well as the treatment with surgery followed by radiation is useful for
      improving the survival outcome.

PMID- 23140039
TI  - The validity of peak nasal inspiratory flow as a screening tool for nasal
      obstruction.
AB  - BACKGROUND: The peak nasal inspiratory flow (PNIF) is used as an outcome measure
      in post-treatment clinical and research evaluation. It is simple and cost
      effective. The validity of the use as a screening tool has never been assessed
      OBJECTIVE: To assess its validity and to define the cut-off point of determining
      the nasal obstruction MATERIAL AND METHOD: The nasal patency of 141 ambulatory
      subjects with or without sino-nasal diseases was measured by the PNIF and active
      anterior rhinomanometry. Inclusion criteria was all subjects aged 18 to 75-years
      old, sinonasal diseases/ symptoms(nasal congestion, nasal discharge, nasal polyp,
      deviated nasal septum, nasal tumor inferior turbinate hypertrophy, sinusitis, and
      allergic rhinitis), instant sensation of nasal obstruction, and nasal endoscopy
      finding were recorded. All subjects signed written consent. Compared with the
      active anterior rhinomanometry as the gold standard, the sensitivity,
      specificity, likelihood ratio, positive predictive value, and negative predictive
      value of the PNIF was analyzed. The cut-off point of nasal obstruction was
      defined from the Receiver Operating Characteristic curve analysis. The agreement
      between the PNIF and the stuffiness and between the PNIF and the presence of sino
      nasal diseases were assessed by using Kappa. RESULTS: With the cut-off point of
      90 L/min, the sensitivity of the peak nasal inspiratory flow was 0.87 (0.753
      0.989). The specificity was 0.52 (0.429-0.617). The negative predictive value was
      0.93 (0.872-0.997). The positive predictive value was 0.34 (0.237-0.446). The
      likelihood ratio was 1.81 (1.438-2.318). The mean of the PNIF in normal subjects
      was 97.11 +/- 31.15. The agreement between the PNIF and the instant sensation of
      nasal blockage was 0.14 (-0.024-0.321) and the agreement between the PNIF and the
      sino-nasal diseases was 0.09 (-0.083-0.265). CONCLUSION: The PNIF regarding the
      cut-off point of 90 L/min, revealed good sensitivity and high negative predictive
      value but it had low specificity and low positive predictive value. The nasal
      peak flow did not agree well with the subjects' symptoms of blockage and sino
      nasal diseases.

PMID- 23140040
TI  - Vascular access stenosis and central vein obstruction interventions: five years
      of experience in Ramathibodi Hospital.
AB  - OBJECTIVE: To evaluate initial post-treatment and six months outcome of patients
      sent to the intervention radiology unit with vascular access malfunctions.
      MATERIAL AND METHOD: A retrospective study of venoplasty, venoplasty with
      stenting, and venoplasty with thrombolysis for vascular access failure patients,
      included 53 patients with 67 interventional radiology procedures at the
      intervention radiology unit of Ramathibodi Hospital between January 2004 and June
      2009. RESULTS: Sixty-seven intervention procedures were performed in 53 patients.
      Two patients had severe stenosis of AVF anastomosis with a resulting in failure
      to perform venoplasty. There were 34 lesions of central venous obstruction. The
      lesions were usually short and 79% shorter than 4.0 cm. In the group of central
      venous obstruction that performed venoplasty alone, the degree of stenosis was
      58.7 +/- 18.6% (mean +/- SD) with 69.2% technical success and 84.6% clinical
      successes. However the technical success was increased to 71.4% and clinical
      success was increased to 100% in the stent placement group. At the six-month
      follow-up, there was no significant clinical re-obstruction. Fair to good
      outcomes of interventional procedures of vascular access and peripheral venous
      stenosis were achieved. Within the group of 14 lesions of patients who underwent
      AVBG, the degree of stenosis was 64.4 +/- 14.4% with 57.1% technical success and
      100% clinical successes. In the other group of 19 lesions that underwent native
      AVF the degree of stenosis was 61 +/- 9.4% with 52.6% technical success and 89%
      clinical successes. Two patients had re-stenosis and thrombosis in AVBG six
      months after treatment procedure. CONCLUSION: Percutaneous interventional
      radiology procedure continues to play a beneficial role in treatment, and remains
      the first treatment of choice in vascular access malfunction and corollary
      complications of central venous obstruction. The technical success rate of
      treatments is determined by morphologic features of each lesion, with the
      identification of these features helping in proper planning and the use of
      appropriate instruments.

PMID- 23140041
TI  - Substance abuse among migrant workers of Thai-Laos border, Thailand.
AB  - OBJECTIVE: Study the impact of substance abuse among migrant workers along the
      Thai-Laos border region in Nakhon Phanom Province. MATERIAL AND METHOD: The
      target population included migrant workers aged 15 years and over and were
      selected using the snowball technique. Data were collected from 300 migrant
      workers and in-depth interviews and focus group discussion were carried out. Data
      analysis used content analysis, descriptive statistics, and multivariate logistic
      regression. RESULTS: Fifty-five point seven percent of migrant workers used
      stimulants namely tobacco, energy drinks, coffee, and methamphetamine. Males were
      at greater risk for substance abuse than females (AOR 16.03; 95% CI 8.43-30.45)
      and those who received news and information from community radios and news
      broadcasting towers were at more risk than other media (AOR 5.38; 95% CI 2.88
      10.05). The impact of substance abuse were found to be chronic cough, moodiness,
      lack of interest in food, headache, wakefulness, sleeplessness, tremor heart
      palpitation, and accidents. CONCLUSION: Health promotion strategy must be
      implemented to minimize the harm. Motivating behavioral modification while
      keeping in mind the lifestyle, work, and environment of these people could help.

PMID- 23140042
TI  - Evaluation of the analytical performance of the nova StatSensor creatinine meter
      for blood testing.
AB  - BACKGROUND AND OBJECTIVE: For reliability of laboratory results, all methods,
      instruments, and reagents should be evaluated The Nova StatSensor creatinine
      meter is a hand-held device for determination of creatinine concentration in the
      whole blood Therefore, the device has to be validated or verified before
      performing. MATERIAL AND METHOD: Observational analysis method with cross
      sectional design was used in this evaluation. The commercial reagents and coded
      samples were prepared for linearity, precision, accuracy, and interference
      studies. RESULTS: The linear measurement range of 1.3 to 9.5 mg/dL was verified
      with the recovery results between 91.6 to 105.0%. Total imprecision demonstrated
      by coefficient of variation (CV) was 6.4 to 8.9 CV%. Linear regression was y =
      0.946x + 0.103, r = 0.992, r2 = 0.984. The bias was calculated from our data
      using regression equation. Our results demonstrated the accuracy was acceptable.
      Glucose level of 200 mg/dL and 400 mg/dL created the high difference between
      baseline creatinine (1.2 mg/dL and 2.8 mg/dL) and creatinine measured in the
      presence of interference was 25.0%, 16.7%, 14.3%, and 19.7% respectively.
      CONCLUSION: Our results demonstrated that the device provides reliable creatinine
      measurement and could be used in point-of-care testing. Use of this device in
      diabetic patients with high glucose level of > or = 200 mg/dL is not recommended

PMID- 23140043
TI  - Quality of life in Thai intractable epileptic patients with and without surgery.
AB  - OBJECTIVE: Assess the quality of life (QoL) of epileptic patients who have and
      have not undertaken epilepsy surgery, in Thailand. MATERIAL AND METHOD:
      Refractory epileptic patients enrolled in the Epilepsy unit, King Chulalongkorn
      Memorial Hospital between 2007 and 2008. They were categorized by their history
      of epilepsy surgery into two groups. Sixty patients who had undergone epilepsy
      surgery for at least one year and another 60 patients who had no previous history
      of surgery, were recruited 60 cases each group from the registered list.
      Demographic data, illness history, psychosocial information, depressive state
      (Hamilton depressive rating scale, Thai-version), and quality of life (WHOQOL
      BREF-26 Thai-version) were comparatively analyzed The association between QOL and
      other factors was determined by t-test or one way ANOVA. Stepwise multiple
      regression also was performed to identify the predictive factor(s) for QoL.
      RESULTS: The outcome indicated that patients who had received surgery had
      significantly higher QoL scores than those without surgery in overall and
      specific domains including physical, psychological, social participating, and
      environmental domains. The mean QoL score in surgery group was also allocated in
      the level of good QoL, compared to Thai general population. There were six
      factors found that associated with QOL by univariate analysis. They were
      undertaken surgery, older age, seizure freedom, duration of illness, good
      relationship with family, and mild/absence of depression. However the
      multivariate analysis shows that only surgery was predicative to improve QoL.
      CONCLUSION: QoL of Thai intractable epileptic patients with surgery was much
      better than those without surgery in four main areas, which are physical,
      psychological, social, and environmental domains.

PMID- 23140044
TI  - [Effect of mild moxibustion on macrophage number and collagen expression of raw
      surface tissue in chronic refractory skin ulcer rats].
AB  - OBJECTIVE: To observe the effect of mild moxibustion on the number of macrophages
      and contents of collagen I and III in the raw surface tissue in chronic skin
      ulcer rats so as to study its mechanism underlying promoting scar formation.
      METHODS: Eighty male SD rats were randomly divided into normal (n = 8), model (n
      = 24), TDP (n = 24) and moxibustion (n = 24) groups. Chronic refractory skin
      ulcer was established by making an open wound at the back and local intramuscular
      injection of hydrocortisone sodium succinate. For rats of the TDP and moxibustion
      groups, TDP irradiation or mild moxibustion was applied to the raw surface,
      bilateral "Shenshu" (BL 23) and "Zusanli" (ST 36) for 15 min, once daily for 7,
      10 and 14 days, respectively. The number of macrophages in the raw surface tissue
      was counted under light microscope after H. E. staining and col- lagen I and III
      expressions of the raw surface tissue were detected by immunohistochemistry.
      RESULTS: In comparison with the normal group, the numbers of macrophages in the
      raw surface tissue were increased significantly in the model group on day 7, 10
      and 14 (P < 0.05); while compared with the model group, the numbers of
      macrophages were increased further obviously in the moxibustion group on day 7
      and 10 and in the TDP group on day 10 after the treatment (P < 0.05). Compared
      with the model group, the numbers of macrophages in both TDP and moxibustion
      groups were down-regulated obviously (P < 0. 05). In regard to collagen I and III
      expression of the raw surface tissue, compared with the normal group, the
      collagen I protein expression level was down-regulated markedly in the model
      group on the 7th day (P < 0.01); whereas in comparison with the model group, the
      expression levels of collagen I and III were increased considerably in the TDP
      and moxibustion groups on day 7 and 14 after the treatment (P < 0.05, P < 0.01).
      The ratios of collagen I/III expression were remarkably higher in the model group
      than in the normal group on day 7 and 14 (P < 0.05), and significantly lower in
      the TDP group on day 7 and 14 and in the moxibustion group on day 14 than in the
      model group (P < 0.05, P < 0.01). The effects of moxibustion were obviously
      superior to those of TDP in up-regulating macrophage number on day 10, up
      regulating collagen I and III expressions on day 14, and down-regulating
      macrophage number on day 14 after the treatment (P < 0.05, P < 0.01). No
      significant differences were found between the TDP and moxibustion groups in up
      regulating macrophage number, and collagen I and III protein expressions, and in
      down-regulating the ratios of collagen I/III expression on day 7 after the
      treatment (P > 0.05). CONCLUSION: Mild moxibustion can regulate the number of
      macrophages and strengthen the expression of collagen proteins in the raw surface
      tissue in the chronic skin ulcer rats, which may contribute to its effect in
      promoting wound healing and reducing scar formation.

PMID- 23140045
TI  - [Effect of electroacupuncture on spleen lymphocyte apoptosis-related gene
      expression in aging rats with yang deficiency].
AB  - OBJECTIVE: To observe effects of electroacupuncture (EA) of "Guanyuan" (GV 4)
      "Housanli" (ST 36)-"Baihui" (GV 20,"Shuanggu Yitong" acupoint prescription) on
      the expression of splenic lymphocyte apoptosis-related genes Fas, Bax, and Bcl-2
      in aging rats with yang defiency. METHODS: Thirty Sprague-Dawley aged female rats
      were randomly and e-ic qually divided into normal control, yang deficiency model
      (model) and EA groups. The yang deficiency model was established by subcutaneous
      injection of D-galactose (125 mg/kg) and hydrocortisone(1.5 mg/100 g). EA (2 Hz,
      1 mA) was applied to "Guanyuan"(GV 4), "Housanli" (ST 36) and "Baihui" (GV 20)
      for 15 min, once daily, 6 times per week for 4 weeks. The expression of pro
      apoptotic genes Fas, Bax and anti-apoptosis gene Bcl-2 in the spleen tissues were
      detected by real-time quantitative RT-PCR. RESULTS: In comparison with the normal
      control group, splenic Fas mRNA and Bax mRNA expression levels were upregulated
      significantly, and Bcl-2 mRNA expression level was down-regulated considerably in
      the model group (P < 0. 01). After EA intervention, splenic Fas mRNA and Bax mRNA
      expression levels were down-regulated markedly, while Bcl-2 mRNA expression up
      regulated remarkably in the EA group (P < 0.05, P < 0.01). CONCLUSION: EA of
      acupoint prescription ["Guanyuan" (GV 4), "Housanli" (ST 36) and "Baihui" (GV
      20)] can down-regulate spleen Fas mRNA and Bax mRNA expression, and up-regulate
      Bcl-2 mRNA expression in aging rats with yang deficiency, which may contribute to
      its effect in improving yang deficiency in clinic.

PMID- 23140046
TI  - [Effects of electroacupuncture and manual acupuncture interventions on contents
      of serum inflammatory cytokines in rats with chronic adjuvant arthritis].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) or manual acupuncture
      of unilateral or bilateral "Zusanli" (ST 36) on the contents of serum
      inflammatory factors interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha
      (TNF-alpha), and anti-inflammatory factors interleukin 2 (IL-2), interleukin 4
      (IL-4) and interleukin 10 (IL-10), so as to reveal their mechanism underlying
      improvement of chronic arthritis. METHODS: Sixty SD rats were randomly divided
      into normal control, model, electroacupuncture (EA)-left (L) Zusanli (ST 36), EA
      bilateral (Bi)-ST 36,and manual acupuncture (MA)-L-ST 36 groups (12 rats/group).
      Arthritis model was established by subcutaneous injection of complete Freund's
      adjuvant (0.1 mL)into the hindpaw. EA (2 Hz/100 Hz, 1-3 mA, pulse duration: 0.6
      ms/0.2 ms) or manual needle stimulation was applied to the left or bilateral
      "Zusanli" (ST 36) for 30 min, twice every week for 4 weeks. Enzyme linked
      immunosorbent assay (ELISA) was used to detect the contents of serum IL-1beta,
      TNF-alpha, IL-2, IL-4 and IL-10, respectively. RESULTS: Compared with the normal
      control group, the contents of serum inflammatory factors IL-1beta and TNF-alpha,
      anti-inflammatory factors IL-4 and IL-10 were increased significantly in the
      model group (P < 0.001). In comparison with the model group, serum IL-1beta, TNF
      alpha, IL-4 and IL-10 contents were down-regulated considerably in the EA-L-ST
      36, EA-Bi-ST 36 and MA-L-ST 36 groups (P < 0.001, P < 0.005). Serum IL-2 content
      had no apparent changes after modeling in comparison with the normal group (P >
      0.05). While serum IL-2 contents were markedly higher in the EA-L-ST 36, EA-Bi-ST
      36 and MA-L-ST 36 groups than in the model group (P < 0.05). No significant
      differences were found among the EA-L-ST 36, EA-Bi-ST 36 and MA-L-ST 36 groups in
      serum IL-1beta, TNF-alpha, IL-2, IL-4 and IL-10 contents (P > 0.05). CONCLUSION:
      EA or manual acupuncture stimulation of single or bilateral ST 36 can effectively
      down-regulate serum inflammatory factors IL-1beta and TNF-alpha levels, and
      upregulate anti-inflammatory factor IL-2 level in chronic arthritis rats, which
      may contribute to their effects in relieving chronic arthritis.

PMID- 23140047
TI  - [Effects of heat and cool-producing needling manipulations on rectal temperature
      and serum endotoxin content in endotoxin-induced heat syndrome rabbits].
AB  - OBJECTIVE: To observe the effect of traditional manipulations of "Shaoshanhuo"
      (heat-producing needling) and "Toutianliang"(cool-producing needling) on body
      temperature and serum endotoxin level in heat syndrome rabbits. METHODS: Twenty
      four Japanese rabbits were randomly divided into control, model, Shaoshanhuo and
      Toutianliang groups. Heat-syndrome model was established by subcutaneous
      injection of bacterium coli endotoxin solution (40 microg/mL, 2 mL/kg). Heat
      producing and cool-producing needling was applied to bilateral "Quchi" (LI 11)
      for 5 min, respectively. Rectal temperature was detected by using a thermometer,
      and serum endotoxin content assayed by using Limulus Ameboyte Lysate kit
      (luminescence measuring). RESULTS: In comparison with the control group, both
      rectal temperature and serum endotoxin levels were increased significantly in the
      model group (P < 0.01). While compared to the model group, the rectal temperature
      and serum endotoxin levels were down-regulated considerably in both Shaoshanhuo
      and Toutianliang groups (P < 0.05, P < 0.01). The effect of the Toutianliang
      group was obviously superior to that of the Shaoshanhuo group in reducing serum
      endotoxin content (P < 0.01). CONCLUSION: Both heat-producing needling and cool
      producing needling can lower rectal temperature and serum endotoxin levels in
      heat-syndrome rabbits, and the effect of cool-producing needling is relatively
      better in reducing endotoxin content.

PMID- 23140048
TI  - [Effect of electroacupuncture at different frequencies on serum estradiol and
      progesterone levels in late-stage pregnancy rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) at different
      frequencies on serum estradiol (E2), progesterone (P), thromboxance B2 (TXB2), 6
      Keton-prostaglandin F 1 alpha (6-keto-PGF1alpha) contents in late pregnancy rats
      so as to study its mechanisms underlying labor promotion. METHODS: A total of 66
      late-stage pregnant Wistar rats were randomly divided into 6 groups: normal
      control, late-pregnancy model (model), 2 Hz-EA, 20 Hz-EA, 50 Hz-EA and 100 Hz-EA
      groups, with 11 rats in each group. On the 19th day after pregnancy, EA (2 Hz, 20
      Hz, 50 Hz, 100 Hz, 0.1 mA) was applied to bilateral "Hegu" (LI 4) for 20 min
      first and to bilateral "Sanyinjiao" (SP 6) for 5 min afterwards. Serum E2, P,
      TXB2 and 6-keto-PGF1alpha contents were assayed by radioimmunoassay, and the
      ratios of E2/P and TXB2/6-keto-PGF1alpha were calculated. RESULTS: Compared to
      the normal control group, serum E2 contents in 2 Hz-EA, 20 Hz-EA, 50 Hz-EA and
      100 Hz-EA groups were increased significantly (P < 0.001, P < 0.01, P < 0.05).
      Compared to the model group, serum E2 levels in the 2 Hz-EA and 20 Hz-EA groups
      were up-regulated further significantly (P < 0.05). Comparison among the four EA
      groups showed that serum P level in the 100 Hz-EA group was significantly higher
      than those in the 20 Hz-EA and 50 Hz-EA groups (P < 0.05). Compared to the normal
      control group, the contents of serum TXB2 and the ratios of E2/P in both 2 Hz-EA
      and 50 Hz-EA groups were significantly higher (P < 0.05, P < 0.001, P< 0.01).
      CONCLUSION: Both 2 Hz and 20 Hz EA can effectively increase serum E2 content, and
      2 Hz and 50 Hz EA can raise serum TXB2 and E2/P levels in late pregnancy rats,
      which may contribute to their effects in strengthening the uterine contractility
      to promote labor by regulating hormone secretion.

PMID- 23140049
TI  - [Effect of electroacupuncture on expression of proliferating cell nuclear antigen
      and glial fibrillary acidic protein in subventricular zone of Parkinson's disease
      rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) on the expression of
      proliferating cell nuclear antigen (PCNA) and glial fibrillary acidic protein
      (GFAP) in the subventricular zone (SVZ) of Parkinson's disease (PD) rats, so as
      to explore its mechanisms underlying improvement of PD. METHODS: Eighteen SD rats
      were randomized into normal control, model and EA groups (6 rats/group). PD model
      was duplicated by microinjection of 6-hydroxydopamine (2.5 microg/microL, 6
      microL) containing 0.02% antiscorbic acid into the right medial forebrain bundle
      region (P: -4. 0, L: 0.8, H: 8.0). On the 7th day after modeling, EA (100 Hz) was
      applied to bilateral "Hegu" (LI 4) and "Taichong" (LR 3) for 30 min, once a day
      for 21 days. The expression levels of tyrosine hydroxylase (TH), GFAP and PCNA in
      the right SVZ tissue were detected by immunohistochemistry. RESULTS: TH
      expression was strong in the normal control group, but no TH expression was found
      in the model and EA groups. In comparison with the normal control group, the
      expression levels of PCNA and GFAP proteins and the number of PCNA-IR-positive
      cells in the right SVZ were decreased significantly in the model group (P <
      0.01); while compared with the model group, the expression levels of PCNA and
      GFAP proteins and the number of PCNA-IR-positive cells in the right SVZ were up
      regulated considerably in the EA group (P < 0.01, P < 0.05). CONCLUSION: EA can
      up-regulate the expression of PCNA and GFAP proteins in the SVZ in PD rats
      without changes of TH expression, which may contribute to its effect in improving
      clinical symptoms of PD.

PMID- 23140050
TI  - [Effects of electroacupuncture of "Weizhong" (BL 40), "Sanyinjiao" (SP 6) and
      "Yinlingquan" (SP 9) on intravesical pressure and bladder adenosine triphosphate
      content in rabbits with acute urinary retention].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Weizhong" (BL
      40), "Sanyinjiao" (SP 6) and "Yinlingquan" (SP 9) on changes of intravesical
      pressure and contents of adenosine triphosphate (ATP) in the urinary bladder
      tissue in rabbits with acute urine retention, so as to explore the relatively
      specificity of acupoints for urinary bladder problems. METHODS: Forty-eight male
      adult rabbits were randomly divided into normal control, model, Weizhong (BL 40,
      EA-BL 40), San-yinjiao (SP 6, EA-SP 6), Yinlingquan (SP9, EA-SP9) and non
      acupoint (EA-NA) groups. Acute urinary retention model was established by filling
      the rabbits' bladder with normal saline at a volume of 2 times above their normal
      capacity for 2 hours. EA (2 Hz/15 Hz, 0.6 mA) was applied to bilateral "Weizhong"
      (BL 40), "Sanyinjiao" (SP 6) and "Yinlingquan" (SP 9) for 20 min, respectively.
      Intravesical pressure was detected by using a pressure transducer and an
      amplifier. Bladder ATP content was detected by using enzyme linked immunosorbent
      assay (ELISA). RESULTS: In comparison with pre-modeling, the intravesical
      pressure levels were decreased significantly after modeling in the model, EA-BL
      40, EA-SP 6, EA-SP 9 and EA-NA groups (P < 0.05). Compared with pre-EA,
      intravesical pressure values were increased remarkably in the EA-BL 40, EA-SP 6,
      EA-SP 9 and EA-NA groups (P < 0.05). The percentages of the increased vesical
      pressure after EA were considerably higher in the EA-BL 40, EA-SP 6, EA-SP 9 and
      EA-NA groups than in the model group (P < 0.05). Compared with the normal group,
      bladder ATP content in the model group was reduced significantly (P < 0.05);
      while in comparison with the model group, ATP contents in the EA-BL 40, EA-SP 6
      and EA-SP 9 groups were up-regulated apparently (P < 0.05). The bladder ATP level
      of the EA-BL 40 group was significantly higher than those of EA-SP 6 and EA-SP 9
      groups (P < 0.05). No significant differences were found between the model and EA
      NA groups, and between the EA-SP6 and EA-SP9 groups in bladder ATP contents (P >
      0.05), and among the EA-BL 40, EA-SP 6 and EA-SP 9 groups in the percentages of
      the increased intravesical pressure (P > 0.05). CONCLUSION: EA of BL 40, SP 6 and
      SP 9 can significantly raise intravesical pressure and bladder ATP content in
      urine retention rabbits, which may contribute to its effect in improving urinary
      retention.

PMID- 23140051
TI  - [Effect of electroacupuncture on ultrastructural changes of facial nerve in
      rabbits with facial nerve injury].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) on ultrastructure of
      facial nerve and Schwann cells in facial nerve injury rabbits so as to explore
      its mechanism underlying improving facial palsy. METHODS: A total of 60 Japanese
      white rabbits were randomly assigned to normal control (normal, n = 6), sham
      operation (sham, n = 18), model (n = 18) and EA (n = 18) groups. The facial nerve
      injury model was established by clamping the right facial nerve for 5 min by
      using a pair of forceps. EA (1.5 V, 3 Hz/60 Hz) was applied to "Yifeng" (TE 17)
      "Hegu" (LI 4), and "Dicang" (ST4)-"Jiache" (ST6) on the affected side for 30 min,
      respectively, once daily for 3 weeks. Morphologic changes of the myelin sheath
      and Schwann cells of the facial nerve were observed by using electron microscope
      after 1, 2 and 3 weeks' treatment. RESULTS: Compared with the normal control
      group, the number of the myelin sheaths and the thickness values of the facial
      nerve after treatment of 1, 2 and 3 weeks in the model group were decreased
      significantly (P < 0.01, P < 0.05). While in comparison with the model group, the
      thickness value of the facial nerve 2 weeks after modeling in EA group was
      increased considerably (P < 0.01). In the model group, there were many vacuoles
      in the cytoplasm of Schwann cells instead of organells in the facial nerve. In
      the sham group, the demyelination was milder than that of the model group, and
      majority of myelin sheaths showed integral structure after 2 and 3 weeks, being
      similar to the normal group. Compared with the model group, the extent of
      demyelination was less distinct, with relatively more abundant organells in the
      facial nerve of the EA group, especially after 1 week of treatment. Among the
      three time points in the EA group, demyelination was milder in the 1st week not
      in the other time points. In contrast, along with the continuous EA treatment,
      the situation became worse after 3 weeks of treatment in the EA group.
      CONCLUSION: In the acute stage of facial nerve injury, EA intervention can play a
      positive effect on the repair of the nerve and Schwann cells. However, continuous
      3- weeks' EA intervention may worsen the facial nerve injury.

PMID- 23140052
TI  - [Effect of acupuncture at different acupoints on expression of hypothalamic GABA
      and GABA(A) receptor proteins in insomnia rats].
AB  - OBJECTIVE: To observe the effect of acupuncture of "Shenmai" (BL 62) and
      "Zhaohai" (KI 6), "Shenmen" (HT 7), etc. on the expression of hypothalamic gamma
      aminobutyric acid (GABA) and GABA(A) receptor (GABA(A)R) proteins in experimental
      insomnia rats so as to explore its mechanism underlying improving sleeping.
      METHODS: Seventy Wistar rats were randomly divided into normal control, model,
      "Sanyinjiao" (SP6), "Neiguan" (PC 6), "Zusanli" (ST 36), "Shenmen" (HT7), and
      "Shenmai" (BL 62)-Zhaohai (KI 6, BL 62-KI 6) groups, with 10 rats in each group.
      Insomnia model was established by intraperitoneal injection of
      chlorophenylalanine solution (PCPA, 1 mL/100 g). An acupuncture needle was
      inserted into each of the bilateral HT 7, PC 6, SP 6, ST 36 and BL 62-KI 6
      respectively and manipulated for about 1 min, once daily for 7 days. Hypothamic
      GABA and GABA(A)R protein expressions were detected by immunohistochemistry. The
      animals' physical ability was evaluated by using pole-climbing test in a water
      tank. RESULTS: In comparison with the normal control group, the numbers of
      hypothalamic GABA immunoreaction (IR)- and GABA(A)R IR-positive neurons and the
      pole-climbing time were reduced significantly in the model group (P < 0.05).
      While in comparison with the model group, the numbers of hypothalamic GABA IR
      positive neurons and those of hypothalamic GABA(A)R IR-positive neurons in the HT
      7, PC 6, SP 6, ST 36 and BL 62-KI 6 groups, as well as the pole-climbing duration
      in the SP 6, ST 36 and BL 62-KI 6 groups were increased considerably (P < 0.05, P
      < 0.01). The effects of HT 7 and BL 62-KI 6 groups were significantly superior to
      those of PC 6, ST 36 and SP 6 groups in up-regulating GABA and GABA(A)R
      expression, and the effect of BL 62-KI 6 group was remarkably better than those
      of HT 7, PC 6, SP 6 and ST 36 groups in lengthening the pole-climbing time (P <
      0.05). CONCLUSION: Acupuncture can effectively suppress insomnia induced down
      regulation of hypothalamic GABA and GABA(A)R in rats and lengthen pole-climbing
      time, which may contribute to its effect in relieving insomnia.

PMID- 23140053
TI  - [Influence of electroacupuncture on spinal TNF-alpha and IL-6 contents in spinal
      cord ischemia-reperfusion injury rabbits].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Zusanli" (ST 36)
      "Quchi" (LI 11) on behavior changes and spinal inflammatory reactions in spinal
      ischemia-reperfusion injury (SI/RI) rabbits, so as to assess its protective
      effect on SI/RI. METHODS: Thirty New Zealand rabbits were randomly divided into
      sham-operation (sham), SI/RI model (model) and EA groups. SI/RI model was
      established by occlusion of the abdominal aorta for 45 min. EA (2 Hz, 1 mA) was
      applied to bilateral "Zusanli" (ST 36)-"Quchi" (LI 11) for 30 min after modeling,
      4 times (0 h, 12 h, 24 h and 36 h after modeling) altogether. The animals' motor
      function score of the hindlimb was assessed according to Tarlov's method. The
      contents of tumor necrosis factor-alpha (TNF-alpha) and Interleukin-6 (IL-6) of
      the lumbar spinal cord tissue were assayed by ELISA 48 h after modeling. RESULTS:
      Compared with the sham group, the animals' motor scores at 24 h and 48 h after
      modeling were decreased, and spinal TNF-alpha and IL-6 contents were increased
      significantly (all P < 0.05) in the model group. In comparison with the model
      group, the animals' motor scores at both 24 h and 48 h were up-regulated
      considerably in the EA group (P < 0.05), suggesting an improvement of the
      neuronal function after EA intervention. The spinal TNF-alpha and IL-6 contents
      were obviously lower in the EA group than in the model group (P < 0.05).
      CONCLUSION: Electroacupuncture has a protective effect on the spinal cord
      ischemia- reperfusion injury of rabbits probably by reducing the local
      inflammatory reactions.

PMID- 23140054
TI  - [Effect of electroacupuncture on cerebral PKC isozyme expression levels in
      cerebral ischemia-reperfusion rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Dingzhongxian"
      (MS 5) and "Dingpangxian" (MS 8) on the expression of cerebral protein kinase C
      (PKC) isozymes in local cerebral ischemia reperfusion injury (CI/RI) rats so as
      to explore its underlying mechanism in protecting ischemic brain tissue. METHODS:
      Seventy-two Wistar rats were randomized into normal control (n = 8), CI/RI model
      (model, n = 32), and EA (n = 32) groups. The later two groups were further
      divided into 4, 12, 24 and 72 h subgroups, respectively, with 8 rats in each.
      CI/RI model was established by occlusion of the middle cerebral artery under
      anesthesia and reperfusion for 4, 12, 24 and 72 h, respectively. EA (1 mA, 2
      Hz/15 Hz) was applied to "Dingzhongxian" (MS5) and "Dingpangxian" (MS8) for 10
      min every time, and once again every 12 h after modeling. The expression of
      PKCgamma and PKCdelta in the ischemic cortex tissue was detected using
      immunohistochemistry. TdT-mediated dUTP Nick-End Labeling was used to detect
      neuronal apoptosis of the local ischemic cerebral cortex. RESULTS: In comparison
      with the normal group, the expression levels of cerebral PKCgamma and PKCdelta
      proteins as well as the number of the apoptotic neurons at time-points of 4, 12,
      24 and 72 h after modeling were increased apparently in the model group (P <
      0.01); while compared with the model group, cerebral PKCgamma and PKCdelta
      protein expressions and the apoptotic neuronal number were decreased considerably
      in the EA group (P < 0.01, P < 0.05). No significant differences were found among
      the 4 time-points in the expression levels of PKCgamma and PKCdelta and apoptotic
      neuronal number in the model group and EA group (P > 0.05). CONCLUSION: EA
      intervention can effectively down-regulate expressions of cerebral PKCgamma,
      PKCdelta proteins and apoptotic neuronal number in cerebral ischemia rats, which
      may contribute to its effect in protecting the ischemic cerebral tissue.

PMID- 23140055
TI  - [Clinical observation on therapeutic effects of mild moxibustion in superficial
      gastritis patients with spleen-stomach deficiency-cold pattern].
AB  - OBJECTIVE: To observe the curative effect of different duration of mild
      moxibustion in superficial gastritis patients with deficiency cold pattern of
      spleen and stomach. METHODS: A total of 84 superficial gastritis patients were
      randomly divided into moxibustion-20 min group, moxibustion-40 min group and
      medication (Ranitidine) group, with 28 cases in each group. Mild moxibustion was
      applied to bilateral Zusanli (ST 36) and Zhongwan (CV 12, odd days), Pishu (BL
      20) and Weishu (BL 21, even-numbered days) for 20 min and 40 min respectively,
      once daily for 20 days. The symptom integrative score of superficial gastritis
      patients and the therapeutic effects were assessed according to "The Scoring
      Table for Symptoms and Signs of Gastrointestinal Disorders of Chinese Medicine",
      etc. RESULTS: Following 20 days' treatment, of the three 28 gastrititis patients
      in the medication, moxibustion-20 min and moxibustion-40 min groups, 0, 1, and 0
      cases were cured, 5, 7 and 12 experienced marked improvement in their symptoms,
      15, 16 and 12 had an improvement, and 8, 4 and 4 were invalid, with the effective
      rates being 71.4%, 85.7% and 85.7%, respectively. After one month's follow up, of
      the three 28 cases in the medication, moxibustion-20 min and moxibustion-40 min
      groups, 0, 4 and 0 cases were cured, 4, 8, and 13 experienced marked improvement,
      15, 16 and 13 had an improvement, 9, 0 and 2 were ineffective, with the effective
      rates being 67.9%, 100% and 92.9%, respectively. Self-comparison of each group
      showed that the integrative scores of symptoms were all decreased significantly
      after the treatment and one-month's follow up in the three groups (P < 0.01). The
      effective rates of both moxibustion-20 min and -40 min were significantly higher
      than that of the medication group after one month's follow up (P < 0.01, P <
      0.05). The therapeutic effect of moxibustion-20 min group was significantly
      superior to that of the medication group in lowering the integrative score of
      symptoms after one month's follow up (P < 0.01). No significant differences were
      found among the three groups in the therapeutic effects and in reducing
      integrative scores of symptoms after 20 days' treatment (P > 0.05). CONCLUSION:
      Mild moxibustion is significantly superior to medication in long-term therapeutic
      effects in the treatment of superficial gastritis patients with spleen-stomach
      deficiency-cold pattern.

PMID- 23140056
TI  - [An instant pain-relief effect of balance acupuncture for relieving sore throat
      in acute pharyngitis patients].
AB  - OBJECTIVE: To observe the instant effect of "Balance Acupuncture" in relieving
      sore throat in patients with acute pharyngitis. METHODS: A total of 74 acute
      pharyngitis patients with sore throat were randomly assigned to treatment group
      (Balance Acupuncture, n = 36) and placebo acupuncture group (sham acupoint, n =
      38). Patients of the Balance Acupuncture group were treated by acupuncture
      stimulation of bilateral "Yantong" (sore throat) point (the mid-point of the
      second metacarpal bone on the radial side) and those of the sham acupoint group
      were treated by acupuncture stimulation of the sham point (the site 1 cm lateral
      to the mid-point between the ulnar endpoint of the cubic transverse striation and
      that of the wrist-palm transverse striation). After insertion, the acupuncture
      needle was manipulated repeatedly till "Deqi" for patients of the treatment group
      but not manipulated for patients of the placebo acupuncture group, then removed
      immediately. The VAS (Visual Analogue Scores) were assessed 1 min after the
      treatment in addition to safety index records. RESULTS: Before the treatment, the
      VAS values of the treatment group and sham acupoint group were (5.25 +/- 1.51)
      points and (4.83 +/- 1.59) points, respectively, which had no significant
      differences between the two groups (P > 0.05). One minute after the treatment,
      VAS values of the treatment and sham acupoint groups were (2.11 +/- 1.88) points
      and (3.39 +/- 1.94) points, respectively, both decreasing significantly (P <
      0.01). The effect of the former group was significantly superior to that of the
      sham acupoint group (P < 0.05). CONCLUSION: Both Balance Acupuncture and sham
      acupoint acupuncture treatments can relieve sore throat in acute pharyngitis
      patients, and the therapeutic effect of Balance Acupuncture treatment is
      obviously better.

PMID- 23140057
TI  - [Analysis on research projects for acupuncture and moxibustion supported by NSFC
      during the 11th 5-year-plan].
AB  - In the present paper, the authors introduce the approved and finished research
      projects for acupuncture and moxibustion therapies supported by the National
      Natural Science Foundation of China (NSFC) during the 11th 5-year-plan. A total
      of 194 research projects were subsidized by NSFC from 2006 to 2010. These
      projects include 6 aspects: meridian-collaterals, acupoint theory, acupuncture
      analgesia, mechanisms underlying improvement of different clinical problems,
      clinical trials, and moxibustion therapy. The research on acupoints has been
      becoming a new hotspot in recent years. Majority of the research projects focus
      on the mechanism of acu-moxibustion underlying improvement of different clinical
      problems, while fewer projects on clinical trials. During the 11th 5-year-plan,
      119 projects were completed; most of them involved meridian-collateral theory,
      acupoint theory, mechanism of acu-moxibustion underlying improvement of clinical
      problems and acupuncture manipulations. Following analysis of the finished
      research projects, we find that 1) many neurobiological methods and techniques
      are commonly used in the research on meridian-collateral theory; 2) the research
      on acupoint theory is changing from observing the local morphological structure
      to identifying characteristics of the regional activated receptors, particularly
      under the circumstances of visceral pathological conditions and efficacies of
      acupoints; 3) researches on the underlying mechanism of acu-moxibusiton for
      improving clinical disorders mainly focused on its cerebral protective effects
      against cerebral ischemia, in addition, researches about other diseases on
      clinical conditions have been also carried out, but the related mechanisms are
      far from understanding; 4) In many research projects, various new methods and
      techniques, such as fMRI, position emission tomography, genomics, proteomics,
      molecular biology, nerve stem cell, etc. were widely used; 5) Randomized
      controlled multi-center clinical trials are definitely insufficient. Only two
      clinical projects were finished during the 11th 5-year-plan. Moreover, it should
      be noted that in the subject of acu-moxibustion, independent innovation
      researches are fewer; the foundation of competitive ability is relatively weaker;
      the supporting conditions for finishing the research projects are poorer in some
      institutes or districts; and the interrelations among the theoretical,
      experimental and clinical researches are not intimately close, leading to
      relative lag in the subject development.

PMID- 23140058
TI  - [Development of studies on bioeffects of ultrasound-acupuncture therapy and its
      underlying mechanism].
AB  - The so-called ultrasound acupuncture is a therapeutic approach for clinical
      problems and health care by applying the ultrasound energy to the acupoints of
      the human body directly or indirectly. It has been applied in clinic for about 30
      years since 1980s. In the present paper, the authors review the development of
      both experimental and clinical researches in the past 30 years. Its clinical
      application includes allergic rhinitis, local pain, mastitis, angina pectoris of
      coronary heart disease, stroke, etc. Regarding the researches on the underlying
      mechanism of ultrasound and ultrasound acupuncture, the authors make a summary
      from 1) bioeffects (thermal and nonthermal effects) of ultrasound intervention;
      2) cell lysis and nonlysis effects of ultrasound intervention; and 3) effects of
      ultrasound acupuncture on the degranulation of mast cells. Based on the idea that
      "inflammatory reaction caused by mast cell degranulation is one of the initial
      factors of acupuncture for inducing therapeutic effects", bioeffects including
      cellular changes, especially mast cell degranulation caused by ultrasound
      stimulation, are thought to be the main possible mechanisms underlying the
      favorable efficacy of ultrasound acupuncture intervention. However, the
      ultrasound metrology and the specific superiority of ultrasound acupuncture
      remain unknown up to now.

PMID- 23140059
TI  - [A review of recent researches on correlation between ATP and acupuncture
      efficacies].
AB  - It has been documented that adenosine triphosphate (ATP) is a multifunctional
      nucleoside triphosphate used in cells, including chemical energy transportation,
      extra- and intracellular signaling, cell structure maintaining, DNA and RNA
      synthesis, etc. In the present paper, the authors reviewed studies on the
      involvement of ATP in different efficacies of acupuncture intervention from the
      following four aspects. 1) ATP release in the stimulated acupoint area is one of
      the key factors for producing acupuncture analgesia; 2) Acupuncture induced
      suppression of ATP activity in the central nervous system results in pain relief;
      3) ATP application on the human body surface may strengthen the sensation
      propagation along the meridian; 4) Favorable regulation of acupuncture
      intervention on the abnormal functional activities of some viscera often
      accompanies with an increase of ATP content and ATPase activity in the related
      internal organs. It has been proposed that ATP, Ca2+ and reactive oxygen species
      (ROS) are closely related each other in the life activities of the organism.
      Hence, a reasonable regulation on ATP levels in the related organs of the body
      may be a new approach for raising clinical therapeutic effects of acupuncture
      therapy.

PMID- 23140060
TI  - Service provision in disaster preparation, response, and recovery for individuals
      with predisaster mental illness.
AB  - Individuals with preexisting mental disorders are at increased risk for negative
      outcomes following a disaster and are one type of vulnerable subpopulation that
      requires special consideration in disaster preparedness, response, and recovery.
      We describe evidence of the increased risk for individuals with predisaster
      mental illness as well as tools for field triage, the critical role of
      partnerships in preparedness and response, and integration of mental health as a
      priority in emergency management systems. Considering individuals with
      predisaster mental disorders at each phase of a disaster may ameliorate some
      negative postdisaster outcomes, such as suicide.

PMID- 23140062
TI  - Occupational and public health considerations for work-hour limitations policy
      regarding public health workers during response to natural and human-caused
      disasters.
AB  - This article examines the occupational health considerations that might impact
      the health and wellbeing of public health workers during responses to natural
      (eg, floods and hurricanes) and human-caused (eg, terrorism, war, and shootings)
      disasters. There are a number of articles in the medical literature that argue
      the impact of how working long hours by house staff physicians, nurses, and first
      responders may pose health and safety concerns regarding the patients being
      treated. The question examined here is how working long hours may pose health
      and/or safety concerns for the public health workers themselves, as well as to
      those in the communities they serve. The health problems related to sleep
      deprivation are reviewed. Current policies and legislations regarding work-hour
      limitations are examined. Policy implications are discussed.

PMID- 23140061
TI  - High-fidelity multiactor emergency preparedness training for patient care
      providers.
AB  - BACKGROUND: Providing comprehensive emergency preparedness training (EPT) for
      patient care providers is important to the future success of emergency
      preparedness operations in the United States. Disasters are rare, complex events
      involving many patients and environmental factors that are difficult to reproduce
      in a training environment. Few EPT programs possess both competency-driven goals
      and metrics to measure life-saving performance during a multiactor simulated
      disaster. METHODS: The development of an EPT curriculum for patient care
      providers-provided first to medical students, then to a group of experienced
      disaster medical providers-that recreates a simulated clinical disaster using a
      combination of up to 15 live actors and six high-fidelity human simulators is
      described. Specifically, the authors detail the Center for Health Professional
      Training and Emergency Response's (CHPTER's) 1-day clinical EPT course including
      its organization, core competency development, medical student self-evaluation,
      and course assessment. RESULTS: Two 1-day courses hosted by CHPTER were conducted
      in a university simulation center. Students who completed the course improved
      their overall knowledge and comfort level with EPT skills. CONCLUSIONS: The
      authors believe this is the first published description of a curriculum method
      that combines high-fidelity, multiactor scenarios to measure the life-saving
      performance of patient care providers utilizing a clinical disaster scenario with
      > 10 patients at once. A larger scale study, or preferably a multicenter trial,
      is needed to further study the impact of this curriculum and its potential to
      protect provider and patient lives.

PMID- 23140063
TI  - Impact of coping styles on post-traumatic stress disorder and depressive symptoms
      among pregnant women exposed to Hurricane Katrina.
AB  - OBJECTIVE: Experiencing natural disasters such as hurricanes is associated with
      post-traumatic stress disorder (PTSD) and depression. We examined the role played
      by perceived stress and coping styles in explaining and modifying this
      association among pregnant women exposed to Hurricane Katrina. DESIGN: The study
      comprised 192 women (133 from New Orleans and 59 from Baton Rouge) who were
      pregnant during Hurricane Katrina or became pregnant immediately after the
      hurricane. Women were interviewed regarding their hurricane experience, perceived
      stress, and mental health outcomes. Coping styles was assessed using the Brief
      COPE, PTSD symptoms using the Post-Traumatic Checklist, and depressive symptoms
      using the Edinburgh Depression Scale. Multivariable regression models were run to
      determine the effects of coping styles on mental health and the interactions
      among coping styles, hurricane experience, and perceived stress on mental health.
      RESULTS: Apart from the positive reframing and humor coping styles, all coping
      styles correlated positively with PTSD or depression (p < 0.05). The instrumental
      support, denial, venting, and behavioral disengagement coping styles were
      significantly associated with worsened PTSD symptoms among those who reported
      higher perceived stress (p < 0.05). Use of a humor coping style seemed to reduce
      the effect of perceived stress on depressive symptoms (p = 0.02 for interaction)
      while use of instrumental support (p = 0.04) and behavioral disengagement (p <
      0.01) were both associated with more symptoms of depression among those who
      perceived more stress. There were no strong interactions between coping style and
      hurricane experience. CONCLUSION: Coping styles are potential moderators of the
      effects of stress on mental health of pregnant women.

PMID- 23140064
TI  - Ethical implications of diversity in disaster research.
AB  - Enhancing the effectiveness, efficiency, and fairness of interventions is an
      increasing source of concern in the field of disaster response. As a result, the
      expansion of the disaster relief evidence base has been identified as a pressing
      need. There has been a corresponding increase in discussions of ethical standards
      and procedures for disaster research. In general, these discussions have focused
      on elucidating how traditional research ethics concerns can be operationalized in
      disaster settings. Less attention has been given to the exploration of the
      ethical implications of heterogeneity within the field of disaster research.
      Hence, while current efforts to discuss the ethics of disaster research in low
      resource settings are very encouraging, it is clear that further initiatives will
      be crucial to promote the ethical conduct of disaster research. In this article,
      we explore how the ethical review of disaster research conducted in low-resource
      settings should account for this diversity. More specifically, we consider how
      the nature of the project (what?), sociopolitical and physical environment of
      research sites (where?), temporal proximity to the disaster event (when?),
      objectives motivating the research (why?), and identity of the stakeholders
      involved in the research process (who?) all relate to the ethics of disaster
      research.

PMID- 23140065
TI  - A quick primer for setting up and maintaining surgical intensive care in an
      austere environment: practical tips from volunteers in a mass disaster.
AB  - The provision of critical care in any environment is resource intensive. However,
      the provision of critical care in an austere environment/mass disaster zone is
      particularly challenging. While providers are well trained for care in a modern
      intensive care unit, they may be under-prepared for resource-poor environments
      where there are limited or unfamiliar equipment and fewer support personnel.
      Based primarily on our experiences at a field hospital in Haiti, we created a
      short guide to critical care in a mass disaster in an austere environment. This
      guide will be useful to the team of physicians, nurses, respiratory care,
      logistics, and other support personnel who volunteer in future critical care
      relief efforts in limited resource settings.

PMID- 23140066
TI  - Evaluating the efficacy of the AAP "pediatrics in disaster" course: the Chinese
      experience.
AB  - OBJECTIVE: "Pediatrics in Disasters" (PEDS) is a course designed by the American
      Academy of Pediatrics to provide disaster preparedness and response training to
      pediatricians worldwide. China has managed to sustain the course and adapt its
      content for local needs. China has also experienced several natural disasters
      since the course's inception, providing an opportunity to evaluate the impact of
      courses that took place in Beijing and Sichuan, in 2008-2010. METHODS: We used
      pretesting/post-testing, participant surveys, and in-depth interviews to evaluate
      whether the course imparted cognitive knowledge, was perceived as useful, and
      fostered participation in relief efforts and disaster preparedness planning.
      RESULTS: In Beijing and Sichuan, post-test scores were 16 percent higher than
      pretest scores. On immediate postcourse surveys, 86 percent of Beijing and
      Sichuan respondents rated the course as very good or excellent. On 6-month
      surveys, participants identified emotional impact of disasters, planning/triage,
      and nutrition as the three most useful course modules. Twelve of 75 (16 percent)
      of Beijing respondents reported direct involvement in disaster response
      activities following the course; eight of 12 were first-time responders.
      Participant interviews revealed a need for more training in providing nutritional
      and psychological support to disaster victims and to train a more diverse group
      of individuals in disaster response. CONCLUSIONS: PEDS imparts cognitive
      knowledge and is highly valued by course participants. Emotional impact of
      disasters, planning/triage, and nutrition modules were perceived as the most
      relevant modules. Future versions of the course should include additional
      emphasis on emotional care for disaster victims and should be extended to a
      broader audience.

PMID- 23140067
TI  - Variations in hypertension-related outcomes among Blacks, Whites and Hispanics in
      two large urban areas and in the United States.
AB  - OBJECTIVE: This study compared the hypertension prevalence, awareness, treatment
      and control in Chicago, Illinois and Detroit, Michigan to that of the general
      United States population (aged > or = 25 years) for the period 2001-2003. We
      examined whether and how much 1) urban populations have less favorable
      hypertension-related outcomes and 2) the rates of racial/ethnic minorities lag
      behind those of Whites in order to determine if the national data understate the
      magnitude of hypertension-related outcomes and racial/ethnic disparities in two
      large cities in the Midwestern region of the United States and perhaps others.
      METHODS: Unstandardized and standardized hypertension-related outcome rates were
      estimated. RESULTS: The hypertension-related outcomes among Chicago and Detroit
      residents lag behind the United States by 8%-14% and 10%-18% points,
      respectively. Additionally, this study highlights the complexity of the
      racial/ethnic differences in hypertension-related outcomes, where within each
      population, Blacks were more likely to have hypertension and to be aware of their
      hypertension status than Whites, and no less likely to be treated. Conversely,
      Hispanics were less likely to have hypertension and also less likely to be aware
      of their status when they do have hypertension when compared to Whites.
      CONCLUSION: At a time when efficacious treatment for hypertension has been
      available for more than 50 years, continued racial/ethnic differences in the
      prevalence, awareness, treatment and control of hypertension is among public
      health's greatest challenges. To achieve the proposed national hypertension
      related goals, future policies must consider the social context of hypertension
      within central cities of urban areas.

PMID- 23140068
TI  - NT-proBNP and potential vascular calcification in Black and Caucasian African
      men: the SAfrEIC study.
AB  - OBJECTIVE: The N-terminal prohormone B-type natriuretic peptide (NT-proBNP) is a
      reliable marker of cardiac strain. In hypertensive heart disease, NT-proBNP
      levels increase and may lose its protective function. Simultaneously, the
      vasculature is also subject to hemodynamic stress, resulting in vascular matrix
      remodeling and stiffening which contribute to further cardiac alterations.
      Alkaline phosphatase (ALP) is a marker of osteoblast activity and is involved in
      vascular calcification. We explored the link between NT-proBNP and ALP in Black
      and Caucasian African men. DESIGN AND MAIN OUTCOME MEASURES: This study included
      128 Black (mean age, 41.1 years) and 118 Caucasian (mean age, 36.4 years) men.
      Conventional measurements were acquired along with serum NT-proBNP and ALP.
      RESULTS: NT-proBNP correlated positively with ALP (r=0.29; p<0.001) in Black
      Africans, but inversely in Caucasians (r=-0.20; p=0.024). After minimal
      adjustment (age, body mass index, systolic blood pressure and arterial
      compliance), the positive significant correlation of NT-proBNP with ALP remained
      in Black men (r=0.225; p=0.014), whereas significance was lost in Caucasian men.
      Multiple regression analyses confirmed the independent association of NT-proBNP
      with ALP in Black men (R2=0.37; beta=0.248; p=0.005), as well as in younger Black
      men (R2=0.26; beta=0.375; p<0.001; n=96), with no significance in Caucasians.
      CONCLUSIONS: NT-proBNP is independently and positively associated with ALP in
      Black African men. This was however not evident in Caucasian men. These results
      suggest that African men are susceptible to potential early vascular
      calcification and may develop increased cardiac afterload prematurely.

PMID- 23140069
TI  - A comparison of metabolic syndrome (MetS) risk factors in Filipino women and
      Filipino American women: a pilot study.
AB  - OBJECTIVE: Cardiovascular disease (CVD) is a significant cause of morbidity and
      mortality in women of Filipino ethnicity. The objective of our work was to
      determine if metabolic syndrome (MetS), a modifiable CVD risk factor, differs in
      women as a function of country of residency and to determine if, CVD prevention
      strategies need to differ for these groups of Filipino women. DESIGN: Data were
      collected in community-based health screenings for this cross-sectional study.
      PARTICIPANTS: PARTICIPANTS were recruited at places of worship in southeast
      United States (n=60) and Central Visayas, Philippines (n=56). MAIN OUTCOME
      MEASURES: Prevalence of MetS and its component factors as defined by the
      International Diabetes Federation criteria. RESULTS: The prevalence of MetS in
      Filipino women (FW) and Filipino American women (FAW) groups was similar (52% vs
      55%, P=.08) although the prevalence of elevated waist circumference was greater
      for FAW (78% vs 59%, P=.03). Conversely, the percentage of FW women with risk
      associated high-density lipoprotein (HDL) levels was higher than the FAW group
      (84% vs 42%, P<.001). Other MetS component factors (blood pressure, glucose and
      triglycerides) did not significantly differ between groups. CONCLUSION: Similar
      high rates of MetS were observed in Filipino women regardless of the country of
      residency although the FAW tended to have higher rates of central obesity while
      the FW tended to have higher rates of risk-associated HDL levels. Further
      research should examine the cause of these differences in order to develop better
      cardiovascular screening and intervention strategies.

PMID- 23140070
TI  - Self-reported sleep impairment and the metabolic syndrome among African
      Americans.
AB  - OBJECTIVES: African Americans (AA) experience a high mortality from
      cardiovascular disease (CVD), even without an increase in the prevalence of the
      metabolic syndrome (MetS). The potential role of sleep impairment in this
      phenomenon has not been studied. The current study examined the relationship
      between self-reported sleep and MetS components among AAs. Sleep variables
      included total sleep quality and specific symptoms: loud snoring, difficulty
      breathing, and sleep duration. DESIGN: Anthropometric (BMI, BP, waist
      circumference, body fat percent) and biologic (fasting glucose, triglycerides,
      total cholesterol, and HDL) measures were obtained from 248 community-recruited
      AA (63% female; mean age 44 years). The Pittsburgh Sleep Quality Index (PSQI), a
      19-item scale with a total sleep quality score and 7 subscales, was used to
      assess self-reported sleep quality. Analyses were controlled for age and sex.
      RESULTS: PSQI total sleep quality predicted neither presence of MetS (Beta=.04,
      P=.29) nor individual CVD variables. However, symptomatic snoring corresponded
      with MetS (Beta=.38, SE=.12, P<.001; OR: 2.57), as well as with fasting glucose,
      BMI, body fat percentage, and waist circumference. CONCLUSIONS: Among AA, overall
      sleep quality as self-reported may not contribute to MetS, but symptomatic
      snoring appears to be important. Further work in this area should focus on sleep
      at the symptomatic level, and include racial and sex variables, as well as
      physiologic and etiologic mechanisms.

PMID- 23140071
TI  - Love your heart: a pilot community-based intervention to improve the
      cardiovascular health of African American women.
AB  - Cardiovascular disease remains the leading cause of death for women, and racial
      and ethnic minority groups disproportionately suffer from cardiovascular risk
      factors. We developed an intensive, culturally-tailored 12-week nutrition and
      physical activity program, Love Your Heart, to reduce cardiovascular risk factors
      for African American women in the Boston area from January to April 2011. The
      pilot study partnered an academic institution with two community-based
      organizations, the Boston Black Women's Health Institute (BBWHI) and Body by
      Brandy Wellness Center (BBBWC). The study sample consisted of 34 women with a
      mean age of 48 years (SD +/- 3), with high rates of hypertension (79%), obesity
      (79%), and elevated waist circumference (94%). Over 12 weeks of follow-up, there
      were substantial reductions in hypertension and elevated waist circumference. We
      found that a culturally tailored weight management program reduced weight and
      cardiovascular risk factors for African American women in an urban community.
      While small, our study suggests that targeted community-based interventions
      focusing on personal and group wellness have the power to reduce health
      disparities and improve cardiovascular health for African American women.

PMID- 23140072
TI  - Exploring the association between reported discrimination and hypertension among
      African Americans: a systematic review.
AB  - BACKGROUND: The experience of racial discrimination among African Americans may
      contribute to an increased risk of developing hypertension and having poor
      hypertension control once diagnosed. Although it is a commonly held belief that
      experiences of discrimination may exert lasting effects on health behavior and
      physiology, the existing evidence is mixed. OBJECTIVE: The objective of this
      review was to identify evidence linking the experience of discrimination with
      hypertension among African Americans and to provide an updated synthesis of the
      literature. DESIGN: Articles for the review were identified through an electronic
      search of PubMed, OVID, and other pertinent journals. The review was augmented
      with a manual search of references. We assessed the quality of included articles
      using modified Downs and Black criteria. RESULTS: In total, 15 articles were
      selected for the review, 12 cross-sectional studies and 3 cohort studies. The
      preponderance of evidence (9 of 15 articles) indicated that discrimination was
      associated with an increased risk of developing hypertension, difficulty
      obtaining control of existing hypertension, and/or elevated blood pressure among
      those without a diagnosis of hypertension. CONCLUSIONS: This systematic review
      supports the association of racial discrimination with an increased risk of
      developing hypertension; however, the picture is not uniform. Methodological
      challenges, such as floor or ceiling effects of reported discrimination and low
      sample size, may have prevented researchers from detecting important
      associations. A better understanding of the emerging but complex relationship
      between discrimination and hypertension among African Americans is needed, as we
      seek to resolve existing cardiovascular health disparities.

PMID- 23140073
TI  - Review: Heart failure with preserved ejection fraction in African Americans.
AB  - Heart failure (HF) affects 5,700 000 people in the United States, with heart
      failure with preserved ejection fraction (HFPEF) being responsible for between
      30%-50% of acute admissions. Epidemiological studies and HF registries have found
      HFPEF patients to be older, hypertensive and to have a history of atrial
      fibrillation. These findings, however, may not be fully applicable to African
      Americans, as they have been poorly studied making up only a minority of the test
      subjects. This review article is intended to discuss the pathophysiology and
      epidemiology of HFPEF within African Americans, highlight the differences
      compared to Caucasian populations and review current treatment guidelines.
      Studies looking at African Americans in particular have shown them to be younger,
      female and have worse diastolic dysfunction compared to Caucasian populations.
      African Americans also have been shown to have a worse mortality outcome
      especially in patients without coronary artery disease. The treatment of HFPEF is
      primarily symptomatic with no survival benefit seen in randomized controlled
      trials. Mechanisms postulated for the worse prognosis in African Americans with
      HFPEF include: greater incidence of hypertension and diastolic dysfunction,
      undefined race-driven genetic predispositions or relative resistance to
      medications that treat HF in general. The biological predispositions may also be
      compounded by inequality of healthcare access; something still felt to exist
      today. Prospective studies and randomized controlled trials need to be conducted
      with particular emphasis on African American populations to fully elucidate this
      disease and to formulate race specific treatment outcomes for the future.

PMID- 23140074
TI  - Rapid growth from 12 to 23 months of life predicts obesity in a population of
      Pacific Island children.
AB  - BACKGROUND: Rapid growth (RG) in early childhood has been associated with
      increased risk of obesity. The specific intervals when risk is highest have not
      been well examined and may help identify modifiable risk factors. OBJECTIVE: To
      determine the correlation between RG in consecutive time intervals during the
      first 2 years of life with obesity at 4-5 years. METHODS: This was a
      retrospective study of children attending the largest community health center in
      Hawaii. Children, aged 4-5 years, with a pre-kindergarten (PreK) well-child
      physical examination were included; data were abstracted from medical charts.
      ANALYSES: Children were classified as overweight (BMI for age/sex 85-94%) or
      obese (BMI for age/sex > or = 95%). Moderate and severe rapid growth was defined
      as an increase in weight-for-height z-score of .67-1.0 SD and > or = 1.0,
      respectively. Relationship between RG and PreK obesity was assessed using
      logistic regression analyses. RESULTS: 389 children were included: 66% Hawaiian,
      21.6% Samoan and 12.3% Filipino. At the PreK 19.6% were obese, and 20.9% were
      overweight. Severe RG from 12 to 23 months was strongly associated with PreK
      obesity (OR 4.36, 95% CI 1.85-10.27). Of children with severe RG from 12-23
      months, 48% were obese at PreK compared with 16.7% of children with moderate RG
      and 19.3% of children without RG. CONCLUSION: Rapid growth between 12 and 23
      months, a key period of nutritional transition in toddlers, was strongly
      associated with obesity at 4 to 5 years of age in this high-risk population of
      Pacific Island minority subgroups.

PMID- 23140075
TI  - Leukocyte count and cardiometabolic risk among healthy participants with parental
      type 2 diabetes: the Pathobiology of Prediabetes in a Biracial Cohort study.
AB  - OBJECTIVE: White blood cell (WBC) count has been associated with cardiometabolic
      risk, but the data for African Americans are conflicting. We determined whether
      WBC count predicts subclinical inflammation and cardiometabolic risk in African
      Americans, despite their known lower WBC count, compared to Caucasians. RESEARCH
      DESIGN AND METHODS: The study cohort consisted of 334 normoglycemic subjects (153
      Caucasian, 181 African American) with parental type 2 diabetes (T2DM), mean (+/-
      SD) age 43.90 +/- 10.25 y and BMI 30.1 +/- 6.84 kg/m2. Each subject underwent
      clinical examination and a standard oral glucose tolerance test (OGTT) to
      document glycemic status. Blood specimens were obtained for determination of WBC
      counts, lipid profile and C-reactive protein (CRP) levels. Metabolic syndrome
      components were identified, using the NCEP cut-offs for waist circumference,
      blood pressure, HDL cholesterol and triglyceride levels. RESULTS: Leukocyte
      counts were lower by approximately 400/cm3 (P=.04) in African Americans than
      Caucasians, and were significantly correlated with waist circumference, HDL
      cholesterol, triglycerides and 2-h OGTT plasma glucose (P=.024-.0009), but not
      blood pressure in both races. Leukocyte counts significantly predicted the
      presence of three or more components of the metabolic syndrome similarly in
      African Americans (P=.0076) and Caucasians (P=.0078), as did CRP levels.
      Leukocyte counts correlated significantly with CRP levels in African Americans
      (r=.30, P<.0001) and Caucasians (r=.29, P=.0003). CONCLUSIONS: Our data indicate
      that WBC count, despite being lower in African Americans than Caucasians,
      predicts low-grade inflammation and cardiometabolic risk with similar magnitude
      in normoglycemic African Americans and Caucasians with parental T2DM.

PMID- 23140076
TI  - Racial/ethnic variation in prevalence estimates for United States prediabetes
      under alternative 2010 American Diabetes Association criteria: 1988-2008.
AB  - OBJECTIVE: To compare the racial/ethnic variation in United States prediabetes
      prevalence estimates for alternative prediabetes definitions currently approved
      by the American Diabetes Association (ADA) across 20 years and in detailed
      multivariate comparisons. DESIGN: Using nationally representative National Health
      and Nutrition Examination Survey (NHANES) data from 1988-2008, we compared trends
      in the prevalence of impaired fasting glucose (IFG) and impaired glycated
      hemoglobin (IGH) for non-Hispanic Black, non-Hispanic White, and Mexican
      American/other Hispanic adults. Using NHANES 2005-2008, we compared prevalence by
      race/ethnicity in more detail for the three current ADA prediabetes definitions-
      IFG, IGH, and impaired glucose tolerance (IGT)--controlling for associated
      factors (education, income, weight, age, sex). RESULTS: Prediabetes prevalence
      during the last 20 years was consistently significantly lower among non-Hispanic
      Blacks compared to non-Hispanic Whites when measured by IFG, but was
      significantly higher among non-Hispanic Blacks when measured by IGH. In adjusted
      models, non-Hispanic Blacks were significantly more likely than non-Hispanic
      Whites to have IGH (OR: 2.22; 95% CI: 1.33-3.70) and less likely to have IFG (OR:
      0.46; 0.30-0.73) or IGT (OR: 0.35; 0.24-0.50), but Mexican American/other
      Hispanic rates did not differ significantly from non-Hispanic White rates.
      However, rates of prediabetes, when defined by any of three individual diagnostic
      criteria, were not statistically significantly different across groups (36.8% for
      non-Hispanic Whites, 36.0% AA, 37.3% Mexican American/other Hispanics).
      CONCLUSIONS: National prediabetes prevalence estimates vary dramatically across
      racial/ethnic groups according to diagnostic method, though over 35% in all three
      racial/ethnic groups met at least one ADA diagnostic criteria for prediabetes.

PMID- 23140077
TI  - Prevalence of diabetes mellitus and diabetic retinopathy in Filipino vs Caucasian
      Americans: a retrospective cross-sectional epidemiologic study of two convenience
      samples.
AB  - OBJECTIVES: To compare the prevalence of diabetic retinopathy in Filipino and
      Caucasian Americans in two clinic populations. DESIGN: Retrospective cross
      sectional epidemiologic study of two convenience samples. PARTICIPANTS AND
      SETTING: Five hundred twelve Filipino and 600 Caucasian patients aged 40 years or
      older examined by two community-based comprehensive ophthalmology clinics during
      a one-year period. RESULTS: The prevalence of self-reported type 2 diabetes
      mellitus among Filipino (F) and Caucasian Americans (C) was 40.6% and 24.8%,
      respectively (P<.001). In the subpopulation with type 2 diabetes mellitus (n=375:
      208 Filipino; 149 Caucasian), there was a statistically insignificant higher
      prevalence of diabetic retinopathy among Filipino diabetics compared to
      Caucasians (F vs C: all forms of diabetic retinopathy, 24.5% vs 16.8%, P=.08; non
      proliferative retinopathy, 17.3% vs 12.8%, P=.24; proliferative retinopathy, 7.2%
      vs. 4.0%, P=.21). In multivariate analyses of the diabetic subpopulation,
      Filipino ethnicity was not a significant predictor of diabetic retinopathy.
      CONCLUSIONS: Filipino Americans may have a higher prevalence of type 2 diabetes
      mellitus and diabetic retinopathy than Caucasian Americans. Among those with type
      2 diabetes, however, Filipino Americans were not found to be more likely to show
      manifestations of diabetic retinopathy than Caucasian Americans.

PMID- 23140078
TI  - Cultural basis for diabetes-related beliefs among low- and high-education African
      American, American Indian, and white older adults.
AB  - OBJECTIVES: Racial and ethnic disparities in diabetes and subsequent
      complications are often attributed to culture; however, previous diabetes
      disparities research is restricted to in-depth ethnic-specific samples or to
      comparative study designs with limited belief assessment. The goal of our study
      was to improve understanding of the cultural basis for variation in diabetes
      beliefs. DESIGN: Cross-sectional. SETTING: Rural North Carolina. PARTICIPANTS:
      Older adults (aged 60+) with diabetes, equally divided by ethnicity (White,
      African American, American Indian) and sex (N=593). INTERVENTIONS: Guided by
      Explanatory Models of Illness and Cultural Consensus research traditions, trained
      interviewers collected data using 38 items in four diabetes belief domains:
      causes, symptoms, consequences, and medical management. Items were obtained from
      the Common Sense Model of Diabetes Inventory (CSMDI). MAIN OUTCOME: Beliefs about
      diabetes. Response options for each diabetes belief item were "agree," "disagree"
      and "don't know." Collected data were analyzed using Anthropac (version 4.98) and
      Latent Gold (version 4.5) programs. RESULTS: There is substantial similarity in
      diabetes beliefs among African Americans, American Indians and Whites. Diabetes
      beliefs were most similar in the symptoms and consequences domains compared to
      beliefs pertaining to causes and medical management. Although some discrete
      beliefs differed by ethnicity, systematic differences by ethnicity were observed
      for specific educational groups. CONCLUSIONS: Socioeconomic conditions influence
      diabetes beliefs rather than ethnicity per se.

PMID- 23140079
TI  - Profile of diabetes mellitus among immigrants from Guyana: epidemiology and
      implications for community action.
AB  - OBJECTIVE: Prompted by anecdotal evidence of a higher rate of type 2 diabetes, we
      set out to investigate the prevalence of diabetes, its risk factors, and co
      morbidities among immigrant Guyanese patients being treated in a family medicine
      health center in Schenectady, New York. METHODS: Patients were ascertained from a
      registration database of all patients aged > or = 30 years who were treated from
      2004 to 2006. We then conducted a detailed retrospective chart review of all
      Guyanese, Caucasian, African American, and Hispanic patients with diabetes and
      randomly selected non-diabetic controls. RESULTS: Of 222 Guyanese patients, 67
      (30.2%) had a diagnosis of diabetes, compared with 47/219 (21.5%) of Hispanics,
      132/777 (17.0%) of African Americans, and 442/2834 (15.6%) of Caucasians
      (P<.0001). Compared with the other racial and ethnic groups, the Guyanese
      diabetic patients were significantly leaner and more likely to be male.
      CONCLUSION: We found a very high prevalence of type 2 diabetes among the Guyanese
      patient population studied and found unique characteristics when compared with
      other ethnic and racial groups. These findings have alerted local clinicians to
      intensify diabetes screening among Guyanese patients. Furthermore, in response to
      these findings, a broad coalition including public health, clinical, and
      community groups has been established with the goal of developing culturally
      appropriate strategies to prevent and control diabetes among Guyanese residents.

PMID- 23140080
TI  - Perception of generic prescription drugs and utilization of generic drug discount
      programs.
AB  - OBJECTIVE: Our study aimed to assess patient's perceptions of generic drugs and
      utilization of generic drug discount programs. DESIGN, SETTING AND PARTICIPANTS:
      A survey was administered to adult participants at community health centers and
      community-based organizations in Houston, Texas, USA (n=525). MAIN OUTCOME
      MEASURES: Multivariate logistic regression was used to quantify the strength of
      association between generic drug perception and utilization of generic drug
      discount programs. RESULTS: Respondents who agreed that "Generic prescription
      drugs are as effective as brand name prescription drugs," were 3 times as likely
      to utilize generic drug discount programs (AOR: 3.0, 95% CI: 1.8-4.8, P<.001).
      Compared to non-Hispanic Whites, African Americans (OR: 10.2; 95% CI: 1.4-76.4)
      and Hispanics (OR: 10.3; 95% CI: 1.3-79.4) were 10 times as likely to agree that
      generic drugs have more side effects than brand name drugs. CONCLUSION:
      Race/ethnicity had no impact in utilization of generic drug discount programs,
      despite racial disparities in perception toward generic drugs' side effects and
      generic drugs being inferior to brand name drugs.

PMID- 23140081
TI  - Health insurance coverage among diabetic adults from three major ethnic groups in
      the United States.
AB  - OBJECTIVE: The lack of adequate health insurance may result in a downward spiral
      of the diabetic condition, imposing an increased financial strain on family and
      the society as a whole. The objective of our study was to assess the insurance
      type and coverage among diabetic adults from three major ethnic groups. DESIGN
      AND SETTING: We used data of two cross-sectional national surveys to estimate
      insurance coverage among diabetic adults aged 20-64 years, 1988-1994 and 2003
      2008. RESULTS: The prevalence of doctor-diagnosed diabetes has increased by 120%,
      178% and 135% respectively among non-Hispanic Whites (NHWs), non-Hispanic Blacks
      (NHBs), and Mexicans & other Hispanics (M&OHs) from 1988-94 to 2003-08. However,
      during the same period, the percentages of diabetic adults covered by health
      insurance declined for all three groups. In the 2003-08 period, 15%, 19% and 40%
      of NHWs, NHBs and M&OHs, respectively, had no insurance. Diabetic NHBs and NHWs
      had an equal likelihood to be covered by government-sponsored programs. However,
      70% of NHWs, in contrast to 37% of NHBs, were covered by private programs
      exclusively. Diabetic M&OHs remained at the lowest likelihood to be covered by
      government-sponsored programs. The diabetic citizen's probability of being
      insured was more than tripled compared with the non-citizens (OR=3.40, 95%=1.42
      8.14). CONCLUSION: Increasing percentages of diabetics had no insurance. Diabetic
      Whites were more likely to be covered by private programs than diabetic Blacks.
      Hispanics were the group falling through the cracks between private programs due
      to low income and government programs because of immigration status.

PMID- 23140082
TI  - Perceived reactions to race and health status in the Massachusetts Behavioral
      Risk Factor Surveillance System Survey.
AB  - OBJECTIVES: Evaluate the relationship between race, perceptions of personally
      mediated racism and health outcomes in the Massachusetts Behavioral Risk Factor
      Surveillance System (BRFSS). METHODS: Regression analysis of 8,266 respondents to
      the Reactions to Race module in 2006 and 2008. Questions assessing personally
      mediated racism were combined to measure perceptions of reactions to race.
      OUTCOME MEASURES: Adjusted odds ratios and 95% CI of perceived personally
      mediated racism, self-reported overall health, life satisfaction, health risks
      (smoking status, obesity, binge and heavy drinking), and preventive services
      (colonoscopy, flu vaccine). RESULTS: Black non-Hispanic respondents are 10.4
      times (95% CI: 6.3-17.3; P<.001) and Hispanics 5.8 times (95% CI: 3.6-9.4;
      P<.001) more likely to report being treated worse than other races compared to
      White non-Hispanic respondents. Respondents of all races reporting being treated
      worse than other races are 3.2 times (95% CI: 1.9-5.4; P<.001) more likely to
      have fair/poor health and 4.1 times (95% CI: 2.1-7.9; P<.001) more likely to
      report life dissatisfaction than those treated the same or better than other
      races. There is no statistically significant association between perceived
      personally mediated racism and health risks or preventive services tested.
      CONCLUSIONS: Perceptions of personally mediated racism are significantly
      associated with fair/poor overall health and life dissatisfaction, but none of
      the health risks or preventive services tested.

PMID- 23140083
TI  - Discrimination, acculturation and other predictors of depression among pregnant
      Hispanic women.
AB  - OBJECTIVE: The purpose of our study was to examine the effects of socioeconomic
      status, acculturative stress, discrimination, and marginalization as predictors
      of depression in pregnant Hispanic women. DESIGN: A prospective observational
      design was used. SETTING: Central and Gulf coast areas of Texas in obstetrical
      offices. PARTICIPANTS: A convenience sample of 515 pregnant, low income, low
      medical risk, and self-identified Hispanic women who were between 22-24 weeks
      gestation was used to collect data. MEASURES: The predictor variables were
      socioeconomic status, discrimination, acculturative stress, and marginalization.
      The outcome variable was depression. RESULTS: Education, frequency of
      discrimination, age, and Anglo marginality were significant predictors of
      depressive symptoms in a linear regression model, F (6, 458) = 8.36, P<.0001.
      Greater frequency of discrimination was the strongest positive predictor of
      increased depressive symptoms. CONCLUSIONS: It is important that health care
      providers further understand the impact that age and experiences of
      discrimination throughout the life course have on depressive symptoms during
      pregnancy.

PMID- 23140084
TI  - Transdisciplinary approaches to understanding and eliminating ethnic health
      disparities: are we on the right track?
AB  - The public health community's struggle to combat domestic health disparities has
      occurred in a context of increasing implementation of transdisciplinary research
      approaches. While conceptually appealing, the focus on the multilevel framing of
      the causes of ethnic health disparities by large-scale transdisciplinary
      initiatives has, to date, resulted in few tangible products. Moreover,
      intervention and community engagement outcomes have received less attention than
      more process-oriented research outcomes, namely assessing levels of
      transdisciplinarity achieved during the research process. We argue that a renewed
      focus on the ultimate products of transdisciplinary approaches, namely effective
      multilevel interventions, specific health outcome improvements, and greater
      community involvement, will aid this promising research paradigm in carrying out
      its philosophical commitment to ending population health disparities.

PMID- 23140085
TI  - Virtual fragment screening: discovery of histamine H3 receptor ligands using
      ligand-based and protein-based molecular fingerprints.
AB  - Virtual fragment screening (VFS) is a promising new method that uses computer
      models to identify small, fragment-like biologically active molecules as useful
      starting points for fragment-based drug discovery (FBDD). Training sets of true
      active and inactive fragment-like molecules to construct and validate target
      customized VFS methods are however lacking. We have for the first time explored
      the possibilities and challenges of VFS using molecular fingerprints derived from
      a unique set of fragment affinity data for the histamine H(3) receptor (H(3)R), a
      pharmaceutically relevant G protein-coupled receptor (GPCR). Optimized FLAP
      (Fingerprints of Ligands and Proteins) models containing essential molecular
      interaction fields that discriminate known H(3)R binders from inactive molecules
      were successfully used for the identification of new H(3)R ligands. Prospective
      virtual screening of 156,090 molecules yielded a high hit rate of 62% (18 of the
      29 tested) experimentally confirmed novel fragment-like H(3)R ligands that offer
      new potential starting points for the design of H(3)R targeting drugs. The first
      construction and application of customized FLAP models for the discovery of
      fragment-like biologically active molecules demonstrates that VFS is an efficient
      way to explore protein-fragment interaction space in silico.

PMID- 23140086
TI  - Epigenetic regulation of nestin expression during neurogenic differentiation of
      adipose tissue stem cells.
AB  - Adipose-tissue-derived stem cells (ASCs) have received considerable attention due
      to their easy access, expansion potential, and differentiation capacity. ASCs are
      believed to have the potential to differentiate into neurons. However, the
      mechanisms by which this may occur remain largely unknown. Here, we show that
      culturing ASCs under active proliferation conditions greatly improves their
      propensity to differentiate toward osteogenic, adipogenic, and neurogenic
      lineages. Neurogenic-induced ASCs express early neurogenic genes as well as
      markers of mature neurons, including voltage-gated ion channels. Nestin, highly
      expressed in neural progenitors, is upregulated by mitogenic stimulation of ASCs,
      and as in neural progenitors, then repressed during neurogenic differentiation.
      Nestin gene (NES) expression under these conditions appears to be regulated by
      epigenetic mechanisms. The neural-specific, but not muscle-specific, enhancer
      regions of NES are DNA demethylated by mitogenic stimulation, and remethylated
      upon neurogenic differentiation. We observe dynamic changes in histone H3K4,
      H3K9, and H3K27 methylation on the NES locus before and during neurogenic
      differentiation that are consistent with epigenetic processes involved in the
      regulation of NES expression. We suggest that ASCs are epigenetically
      prepatterned to differentiate toward a neural lineage and that this prepatterning
      is enhanced by demethylation of critical NES enhancer elements upon mitogenic
      stimulation preceding neurogenic differentiation. Our findings provide molecular
      evidence that the differentiation repertoire of ASCs may extend beyond mesodermal
      lineages.

PMID- 23140087
TI  - Balance control contributors - the relationships between leg strength and balance
      control ability in seniors.
AB  - The paper presents a study on leg strength as a balance control ability
      contributor. 9 seniors with the average age of 69.8 years participated in the
      experimental study. A psychomotor efficiency timer and a standard stabilograph
      were used in the study. The timer consisted of a computer, a controller and an
      arm and leg strength measurement station. The subjects performed stepping up
      movements with the left and right leg in response to two audio-visual signals.
      The strength of legs was measured indirectly by the time of straightening the
      first leg put on the step-box. The balance control ability was tested on the
      basis of the length of the line of center pressure oscillations in the standing
      position on a force platform. The relationships between the tested factors were
      examined on the basis of Pearson's correlation. We have found a strong
      correlation between the balance control ability and the left (0.77) and the right
      (0.83) leg relative strength and correlation between the strength of the left and
      the right leg (0.95). Our study has shown that relative leg strength may be
      treated as a contributor to postural balance control ability.

PMID- 23140088
TI  - Exploring the energy landscape of the charge transport levels in organic
      semiconductors at the molecular scale.
AB  - The extraordinary semiconducting properties of conjugated organic materials
      continue to attract attention across disciplines including materials science,
      engineering, chemistry, and physics, particularly with application to organic
      electronics. Such materials are used as active components in light-emitting
      diodes, field-effect transistors, or photovoltaic cells, as a substitute for
      (mostly Si-based) inorganic semiconducting materials. Many strategies developed
      for inorganic semiconductor device building (doping, p-n junctions, etc.) have
      been attempted, often successfully, with organics, even though the key electronic
      and photophysical properties of organic thin films are fundamentally different
      from those of their bulk inorganic counterparts.  In particular, organic
      materials consist of individual units (molecules or conjugated segments) that are
      coupled by weak intermolecular forces. The flexibility of organic synthesis has
      allowed the development of more efficient opto-electronic devices including
      impressive improvements in quantum yields for charge generation in organic solar
      cells and in light emission in electroluminescent displays. Nonetheless, a number
      of fundamental questions regarding the working principles of these devices remain
      that preclude their full optimization.  For example, the role of intermolecular
      interactions in driving the geometric and electronic structures of solid-state
      conjugated materials, though ubiquitous in organic electronic devices, has long
      been overlooked, especially when it comes to these interfaces with other
      (in)organic materials or metals. Because they are soft and in most cases
      disordered, conjugated organic materials support localized electrons or holes
      associated with local geometric distortions, also known as polarons, as primary
      charge carriers. The spatial localization of excess charges in organics together
      with low dielectric constant (epsilon) entails very large electrostatic effects.
      It is therefore not obvious how these strongly interacting electron-hole pairs
      can potentially escape from their Coulomb well, a process that is at the heart of
      photoconversion or molecular doping. Yet they do, with near-quantitative yield in
      some cases. Limited screening by the low dielectric medium in organic materials
      leads to subtle static and dynamic electronic polarization effects that strongly
      impact the energy landscape for charges, which offers a rationale for this
      apparent inconsistency.  In this Account, we use different theoretical approaches
      to predict the energy landscape of charge carriers at the molecular level and
      review a few case studies highlighting the role of electrostatic interactions in
      conjugated organic molecules. We describe the pros and cons of different
      theoretical approaches that provide access to the energy landscape defining the
      motion of charge carriers. We illustrate the applications of these approaches
      through selected examples involving OFETs, OLEDs, and solar cells. The three
      selected examples collectively show that energetic disorder governs device
      performances and highlights the relevance of theoretical tools to probe energy
      landscapes in molecular assemblies.

PMID- 23140089
TI  - Laboratory diagnosis of swine flu: a review.
AB  - Human swine influenza A [H1N1], also referred to as "swine flu," is highly
      transmissible. The emergence of new strains will continue to pose challenges to
      public health and the scientific communities will have to prepare to detect them
      for appropriate treatment. Most sophisticated methods include immunofluorescence
      staining and antigen subtyping based on hemagglutination inhibition (HI). Another
      standard method is RT-PCR targeting hemagglutinin and neuraminidase genes. The
      recent availability of rapid, reliable, and easy-to-perform tests for detecting
      influenza virus infections has introduced rapid viral diagnosis. This review thus
      summarizes the current information on the present diagnostic methods for
      influenza virus H1N1.

PMID- 23140090
TI  - Evaluation of a single preoperative dose of etoricoxib for postoperative pain
      relief in therapeutic knee arthroscopy: a randomized trial.
AB  - BACKGROUND AND PURPOSE Analgesics can have undesirable effects. We assessed
      whether a single preoperative dose of 120 mg etoricoxib reduces the need for
      additional opioids after therapeutic arthroscopic knee surgery. METHODS A double
      blind, placebo-controlled study was performed at a single center. 66 patients
      scheduled to undergo elective therapeutic knee arthroscopy were included. They
      were randomly selected to be given either 120 mg of etoricoxib (n = 33) or
      placebo (n = 33) 1 hour before induction of general anesthesia. A patient
      controlled analgesia device was used postoperatively. We recorded total
      postoperative morphine consumption over 24 h, degree of pain as assessed with a
      visual analog scale, degree of satisfaction, and occurrence of adverse effects.
      RESULTS Mean total morphine consumption during the first 24 h was 24 (9-60) mg in
      the placebo group and 9 (0-34) mg in the etoricoxib group. In the etoricoxib
      group, pain intensity levels at rest were reduced and patient satisfaction with
      the analgesia provided was higher during the first postoperative day. There was
      no difference in the incidence of typical adverse effects of opioids in the 2
      groups. INTERPRETATION: Etoricoxib is a suitable premedication to use before
      therapeutic arthroscopic knee surgery, as it reduced patients' morphine
      requirements.

PMID- 23140091
TI  - Early migration of tibial components is associated with late revision: a
      systematic review and meta-analysis of 21,000 knee arthroplasties.
AB  - PURPOSE: We performed two parallel systematic reviews and meta-analyses to
      determine the association between early migration of tibial components and late
      aseptic revision. METHODS: One review comprised early migration data from
      radiostereometric analysis (RSA) studies, while the other focused on revision
      rates for aseptic loosening from long-term survival studies. Thresholds for
      acceptable and unacceptable migration were determined according to that of
      several national joint registries: < 5% revision at 10 years. RESULTS: Following
      an elaborate literature search, 50 studies (involving 847 total knee prostheses
      (TKPs)) were included in the RSA review and 56 studies (20,599 TKPs) were
      included in the survival review. The results showed that for every mm increase in
      migration there was an 8% increase in revision rate, which remained after
      correction for age, sex, diagnosis, hospital type, continent, and study quality.
      Consequently, migration up to 0.5 mm was considered acceptable during the first
      postoperative year, while migration of 1.6 mm or more was unacceptable. TKPs with
      migration of between 0.5 and 1.6 mm were considered to be at risk of having
      revision rates higher than 5% at 10 years. INTERPRETATION: There was a clinically
      relevant association between early migration of TKPs and late revision for
      loosening. The proposed migration thresholds can be implemented in a phased,
      evidence-based introduction of new types of knee prostheses, since they allow
      early detection of high-risk TKPs while exposing only a small number of patients.

PMID- 23140092
TI  - Metal-on-metal joint bearings and hematopoetic malignancy.
AB  - This is a review of the hip arthroplasty era. We concentrate on new metal
      bearings, surface replacements, and the lessons not learned, and we highlight
      recent reports on malignancies and joint implants. A low incidence of blood
      malignancies has been found in bone marrow taken at prosthetic surgery. The
      incidence is increased after replacement with knee implants that release very low
      systemic levels of metal ions. A carcinogenic effect of the high levels of metal
      ions released by large metal-on-metal implants cannot be excluded. Ongoing
      Swedish implant registry studies going back to 1975 can serve as a basis for
      evaluation of this risk.

PMID- 23140093
TI  - Patient-related risk factors for fracture-healing complications in the United
      Kingdom General Practice Research Database.
AB  - BACKGROUND AND PURPOSE: A variety of risk factors have been hypothesized to
      contribute to the development of fracture-healing complications; however,
      population-based estimates of the strength of these risk factors are limited. In
      this case-control study, we evaluated patient-related risk factors for fracture
      healing complications. METHODS: Using the United Kingdom General Practice
      Research Database, we identified patients with a fracture-healing complication
      (delayed union, nonunion, or malunion) between 1988 and 2008. 4 controls (i.e.
      patients with normal healing) were matched to each case on general practice,
      fracture site, fracture date, and length of history in the database. We used
      conditional logistic regression to estimate odds ratios (ORs) of various risk
      factors, including demographics, comorbidities, and medication use. RESULTS:
      Diabetes and use of non-steroidal anti-inflammatory drugs (NSAIDs) within 12
      months before the initial fracture were associated with a higher odds of a
      fracture-healing complication (type-I diabetes: adjusted OR = 2.3, 95% CI: 1.3
      3.8; type-II diabetes: adjusted OR = 2.3, CI: 1.4-3.7; NSAIDs: adjusted OR = 2.6,
      CI: 2.1-3.2). Patients who had a motor vehicle accident recorded within 1 month
      before their initial fracture were also at increased odds of a fracture-healing
      complication (adjusted OR = 2.6, CI: 1.2-5.4). INTERPRETATION: Diabetes, NSAID
      use, and a recent motor vehicle accident were most consistently associated with
      an increased risk of a fracture-healing complication, regardless of fracture site
      or specific fracture-healing complication. This analysis suggests that certain
      patient-related characteristics influence the development of fracture-healing
      complications in general, even though specific healing complications may differ
      by their mechanism.

PMID- 23140094
TI  - Breast self-examination and breast cancer awareness in women in developing
      countries: a survey of women in Buea, Cameroon.
AB  - BACKGROUND: Breast cancer is one of the leading causes of cancer morbidity and
      mortality worldwide. In Cameroon, breast cancer causes as many as 10.7 deaths per
      100,000 women making it the second cause of cancer mortality. Better documenting
      women's knowledge and practices on breast cancer and breast self-exam (BSE) would
      be useful in the design of interventions aimed at preventing breast cancer. This
      study sought to 1. describe Cameroonian women's knowledge of breast self
      examination (BSE); 2. assess their impression on the practice of BSE and 3.
      describe their perceptions on the causes, risk factors and prevention of breast
      cancer. METHODS: A cross-sectional survey was conducted in a volunteer sample of
      120 consenting women in Buea, Cameroon. Data were collected using a structured
      questionnaire self-administered by study participants. RESULTS: The sample was
      fairly educated with close to three quarters (70.83%) having completed high
      school. Nearly three quarters (74.17%) of participants had previously heard about
      BSE, however as many as 40% had never done a BSE. Although 95% of participants
      believed that breast cancer could be prevented, only 36.67% recognized breast
      examination as a prevention method. A substantial 13.33% thought that breast
      cancer could be prevented with a vaccine while 45% thought that dieting or
      exercising would prevent breast cancer. Similarly, 70% of participants thought
      that breast cancer could be treated, with 35.83% thinking that it could be
      treated medically while 34.17% thought it could be treated traditionally or
      spiritually. CONCLUSIONS: The practice of BSE while perceived as being important
      is not frequent in these women in Buea, Cameroon. Health education campaigns are
      imperative to elucidate the public on the causes, risk factors and prevention of
      breast cancer. Further studies need to explore what interventions could be best
      used to improve the uptake and practice of BSE.

PMID- 23140095
TI  - Prognostic value of melanoma-associated antigen A9 in renal cell carcinoma.
AB  - OBJECTIVE: The aim of this study was to evaluate the prognostic relevance of
      melanoma-associated antigen (MAGE) A9 in renal cell carcinoma (RCC). MATERIAL AND
      METHODS: Immunohistochemical staining for MAGE A9 was evaluated in a tissue
      microarray containing 587 RCC tumour tissue samples. Nuclear MAGE A9 expression
      was reviewed using a semiquantitative score. Follow-up has been surveyed since
      1990 in a prospectively conducted tumour database. The effect of MAGE A9
      expression on cancer-specific survival (CSS) was assessed by univariate and
      multivariate Cox regression analyses. Subgroup analyses were performed for non
      metastatic and metastatic disease. RESULTS: Median age in all patients was 63.2
      years, 354 patients were male and 233 female, and 108 patients had metastatic
      disease. Median follow-up was 5.6 years for all patients and 9.0 years for
      patients still alive (range 0-19.9 years). High nuclear MAGE A9 expression was
      present in 326 tumour specimens (55.5%). In multivariate analyses high nuclear
      MAGE A9 expression was associated with poor CSS (p = 0.0027). Furthermore, tumour
      stage, lymph-node and distant metastasis, Fuhrman grade G3/4, Karnofsky index <
      80% and male gender were associated with poor CSS. In subgroup analyses, results
      were concordant for patients with non-metastatic disease. In patients with
      metastatic disease, only Karnofsky index > 80% was a significant predictor for
      CSS; MAGE A9 expression could not be shown to be associated with CSS (p = 0.161).
      CONCLUSIONS: High nuclear MAGE A9 expression is independently associated with
      poor CSS in patients with non-metastatic RCC. The assessment of MAGE A9
      expression can provide additional prognostic information and should be used in
      decision-making regarding adjuvant therapy in patients with non-metastatic
      disease.

PMID- 23140096
TI  - Leaf endophyte load influences fungal garden development in leaf-cutting ants.
AB  - BACKGROUND: Previous work has shown that leaf-cutting ants prefer to cut leaf
      material with relatively low fungal endophyte content. This preference suggests
      that fungal endophytes exact a cost on the ants or on the development of their
      colonies. We hypothesized that endophytes may play a role in their host plants'
      defense against leaf-cutting ants. To measure the long-term cost to the ant
      colony of fungal endophytes in their forage material, we conducted a 20-week
      laboratory experiment to measure fungal garden development for colonies that
      foraged on leaves with low or high endophyte content. RESULTS: Colony mass and
      the fungal garden dry mass did not differ significantly between the low and high
      endophyte feeding treatments. There was, however, a marginally significant trend
      toward greater mass of fungal garden per ant worker in the low relative to the
      high endophyte treatment. This trend was driven by differences in the fungal
      garden mass per worker from the earliest samples, when leaf-cutting ants had been
      foraging on low or high endophyte leaf material for only 2 weeks. At two weeks of
      foraging, the mean fungal garden mass per worker was 77% greater for colonies
      foraging on leaves with low relative to high endophyte loads. CONCLUSIONS: Our
      data suggest that the cost of endophyte presence in ant forage material may be
      greatest to fungal colony development in its earliest stages, when there are few
      workers available to forage and to clean leaf material. This coincides with a
      period of high mortality for incipient colonies in the field. We discuss how the
      endophyte-leaf-cutter ant interaction may parallel constitutive defenses in
      plants, whereby endophytes reduce the rate of colony development when its risk of
      mortality is greatest.

PMID- 23140097
TI  - Transcriptomic and phylogenetic analysis of Culex pipiens quinquefasciatus for
      three detoxification gene families.
AB  - BACKGROUND: The genomes of three major mosquito vectors of human diseases,
      Anopheles gambiae, Aedes aegypti, and Culex pipiens quinquefasciatus, have been
      previously sequenced. C. p. quinquefasciatus has the largest number of predicted
      protein-coding genes, which partially results from the expansion of three
      detoxification gene families: cytochrome P450 monooxygenases (P450), glutathione
      S-transferases (GST), and carboxyl/cholinesterases (CCE). However, unlike An.
      gambiae and Ae. aegypti, which have large amounts of gene expression data, C. p.
      quinquefasciatus has limited transcriptomic resources. Knowledge of complete gene
      expression information is very important for the exploration of the functions of
      genes involved in specific biological processes. In the present study, the three
      detoxification gene families of C. p. quinquefasciatus were analyzed for
      phylogenetic classification and compared with those of three other dipteran
      insects. Gene expression during various developmental stages and the differential
      expression responsible for parathion resistance were profiled using the digital
      gene expression (DGE) technique. RESULTS: A total of 302 detoxification genes
      were found in C. p. quinquefasciatus, including 71 CCE, 196 P450, and 35
      cytosolic GST genes. Compared with three other dipteran species, gene expansion
      in Culex mainly occurred in the CCE and P450 families, where the genes of alpha
      esterases, juvenile hormone esterases, and CYP325 of the CYP4 subfamily showed
      the most pronounced expansion on the genome. For the five DGE libraries, 3.5-3.8
      million raw tags were generated and mapped to 13314 reference genes. Among 302
      detoxification genes, 225 (75%) were detected for expression in at least one DGE
      library. One fourth of the CCE and P450 genes were detected uniquely in one
      stage, indicating potential developmentally regulated expression. A total of 1511
      genes showed different expression levels between a parathion-resistant and a
      susceptible strain. Fifteen detoxification genes, including 2 CCEs, 6 GSTs, and 7
      P450s, were expressed at higher levels in the resistant strain. CONCLUSIONS: The
      results of the present study provide new insights into the functions and
      evolution of three detoxification gene families in mosquitoes and comprehensive
      transcriptomic resources for C. p. quinquefasciatus, which will facilitate the
      elucidation of molecular mechanisms underlying the different biological
      characteristics of the three major mosquito vectors.

PMID- 23140098
TI  - Plasmin and the thrombin-thrombomodulin complex both contribute to thrombin
      activatable fibrinolysis inhibitor activation in whole blood model thrombi.

PMID- 23140099
TI  - Sensitive cylindrical SERS substrate array for rapid microanalysis of
      nucleobases.
AB  - In this work, a cylindrical-substrate array for surface-enhanced Raman scattering
      (SERS) measurements was developed to enable analysis of nucleobases in a few
      microliters of liquid. To eliminate uncertainties associated with SERS detection
      of aqueous samples, a new type of cylindrical SERS substrate was designed to
      confine the aqueous sample at the tip of the SERS probe. Poly(methyl
      methacrylate) (PMMA) optical fibers in a series of different diameters were used
      as the basic substrate. A solution of poly(vinylidene fluoride)/dimethylformamide
      (PVDF/DMF) was used to coat the tip of each fiber to increase the surface
      roughness and facilitate adsorption of silver nanoparticles (AgNPs) for enhancing
      Raman signals. A chemical reduction method was used to form AgNPs in and on the
      PVDF coating layer. The reagents and reaction conditions were systematically
      examined with the aim of estimating the optimum parameters. Unlike the spreading
      of aqueous sample on most SERS substrates, particularly flat ones, the new SERS
      substrates showed enough hydrophobicity to restrict aqueous sample to the tip
      area, thus enabling quantitative analysis. The required volume of sample could be
      as low as 1 MUL with no need for a drying step in the procedure. By aligning the
      cylindrical SERS substrates into a solid holder, an array of cylindrical
      substrates was produced for mass analysis of aqueous samples. This new substrate
      improves both reproducibility and sensitivity for detection in aqueous samples.
      The enhancement factor approaches 7 orders in magnitude with a relative standard
      error close to 8%. Using the optimized conditions, nucleobases of adenine,
      cytosine, thymine, and uracil could be detected with limits approaching a few
      hundreds nanomolar in only a few microliters of solution.

PMID- 23140100
TI  - Social, psychological and economic challenges faced by transgender individuals
      and their significant others: gaining insight through personal narratives.
AB  - Using narrative analysis, this study uses survey data to explore the social,
      psychological and economic challenges faced by transgender individuals and their
      significant others. With over 300 participants, this study not only validates the
      findings of previous yet smaller scale studies surrounding the transgender
      experience, it adds greater context to our current understanding, specifically
      because of its inclusion of significant others. Findings include participants'
      reports of social stigma coupled with psychological pain and economic hardship.
      The authors discuss the intersectionality of these three variables and the
      possible implications for understanding the transgender experience and that of
      their partners.

PMID- 23140101
TI  - The wicked problem of China's disappearing coral reefs.
AB  - We examined the development of coral reef science and the policies, institutions,
      and governance frameworks for management of coral reefs in China in order to
      highlight the wicked problem of preserving reefs while simultaneously promoting
      human development and nation building. China and other sovereign states in the
      region are experiencing unprecedented economic expansion, rapid population
      growth, mass migration, widespread coastal development, and loss of habitat. We
      analyzed a large, fragmented literature on the condition of coral reefs in China
      and the disputed territories of the South China Sea. We found that coral
      abundance has declined by at least 80% over the past 30 years on coastal fringing
      reefs along the Chinese mainland and adjoining Hainan Island. On offshore atolls
      and archipelagos claimed by 6 countries in the South China Sea, coral cover has
      declined from an average of >60% to around 20% within the past 10-15 years.
      Climate change has affected these reefs far less than coastal development,
      pollution, overfishing, and destructive fishing practices. Ironically, these
      widespread declines in the condition of reefs are unfolding as China's research
      and reef-management capacity are rapidly expanding. Before the loss of corals
      becomes irreversible, governance of China's coastal reefs could be improved by
      increasing public awareness of declining ecosystem services, by providing
      financial support for training of reef scientists and managers, by improving
      monitoring of coral reef dynamics and condition to better inform policy
      development, and by enforcing existing regulations that could protect coral
      reefs. In the South China Sea, changes in policy and legal frameworks, refinement
      of governance structures, and cooperation among neighboring countries are
      urgently needed to develop cooperative management of contested offshore reefs.

PMID- 23140102
TI  - Micro and nanosystems for delivering local anesthetics.
AB  - INTRODUCTION: One of the most common strategies for pain control during and after
      surgical procedures is the use of local anesthetics. Prolonged analgesia can be
      safely achieved with drug delivery systems suitably chosen for each local
      anesthetic agent. AREAS COVERED: This review considers drug delivery formulations
      of local anesthetics designed to prolong the anesthetic effect and decrease
      toxicity. The topics comprise the main drug delivery carrier systems (liposomes,
      biopolymers, and cyclodextrins) for infiltrative administration of local
      anesthetics. A chronological review of the literature is presented, including
      details of formulations as well as the advantages and pitfalls of each carrier
      system. The review also highlights pharmacokinetic data on such formulations, and
      gives an overview of the clinical studies published so far concerning pain
      control in medicine and dentistry. EXPERT OPINION: The design of novel drug
      delivery systems for local anesthetics must focus on how to achieve higher
      uploads of the anesthetic into the carrier, and how to sustain its release. This
      comprehensive review should be useful to provide the reader with the current
      state-of-art regarding drug delivery formulations for local anesthetics and their
      possible clinical applications.

PMID- 23140103
TI  - Synthesis of crystalline and amorphous, particle-agglomerated 3-D nanostructures
      of Al and Si oxides by femtosecond laser and the prediction of these particle
      sizes.
AB  - We report a single step technique of synthesizing particle-agglomerated,
      amorphous 3-D nanostructures of Al and Si oxides on powder-fused aluminosilicate
      ceramic plates and a simple novel method of wafer-foil ablation to fabricate
      crystalline nanostructures of Al and Si oxides at ambient conditions. We also
      propose a particle size prediction mechanism to regulate the size of vapor
      condensed agglomerated nanoparticles in these structures. Size characterization
      studies performed on the agglomerated nanoparticles of fabricated 3-D structures
      showed that the size distributions vary with the fluence-to-threshold ratio. The
      variation in laser parameters leads to varying plume temperature, pressure,
      amount of supersaturation, nucleation rate, and the growth rate of particles in
      the plume. The novel wafer-foil ablation technique could promote the
      possibilities of fabricating oxide nanostructures with varying Al/Si ratio, and
      the crystallinity of these structures enhances possible applications. The
      fabricated nanostructures of Al and Si oxides could have great potentials to be
      used in the fabrication of low power-consuming complementary metal-oxide
      semiconductor circuits and in Mn catalysts to enhance the efficiency of oxidation
      on ethylbenzene to acetophenone in the super-critical carbon dioxide.

PMID- 23140104
TI  - Strength and thickness of the layer of materials used for ceramic veneers
      bonding.
AB  - The use of adhesive bonding systems and composites in prosthetic dentistry
      brought improved and more aesthetic prosthetic restorations. The adhesive bonding
      of porcelain veneers is based on the micromechanical and chemical bond between
      tooth surface, cement layer and ceramic material. The aim of the study was to
      measure the thickness of the material layer formed during cementing of a ceramic
      restoration, and - in the second part of the study - to test tension of these
      cements. The materials investigated comprised dual-curing materials: Variolink
      II, KoNroot Cem, KoNroot Cem Viscous and Panavia F 2.0, as well as a light-curing
      composite: Variolink Veneer. The thickness was measured with the use of ZIP Lite
      250 optical gauging apparatus. SEM microscope - Hitachi Tabletop Microscope TM
      100 - was used to analyse the characteristics of an adhesive bond and filler
      particle size of particular materials. Tension tests of the cements under study
      were carried out on the MTS Q Test 10 static electrodynamic apparatus. The tests
      showed that KoNroot Cem exhibited the best mechanical properties of bonding to
      enamel and dentin among the materials tested. Variolink II base light-curing
      cement formed the thinnest layer. All the materials tested formed the layer not
      exceeding 1/3 of ceramic restoration thickness.

PMID- 23140105
TI  - Validity, reliability, and responsiveness of a self-reported foot and ankle score
      (SEFAS).

PMID- 23140106
TI  - Is mortality after hip fracture associated with surgical delay or admission
      during weekends and public holidays? A retrospective study of 38,020 patients.
AB  - BACKGROUND AND PURPOSE: Hip fractures are associated with high mortality, but the
      cause of this is still not entirely clear. We investigated the effect of surgical
      delay, weekends, holidays, and time of day admission on mortality in hip fracture
      patients. PATIENTS AND METHODS: Using data from the Danish National Indicator
      Project, we identified 38,020 patients admitted from 2003 to 2010. Logistic
      regression analysis was used to study the association between sex, age, weekend
      or holiday admission, night-time admission, time to surgery, and ASA score on the
      one hand and mortality on the other. RESULTS: The risk of death in hospital
      increased with surgical delay (odds ratio (OR) = 1.3 per 24 h of delay), ASA
      score (OR (per point added) = 2.3), sex (OR for men 2.2), and age (OR (per 5
      years) = 1.4). The mortality rate for patients admitted during weekends or public
      holidays, or at night, was similar to that found for those admitted during
      working days. INTERPRETATION: Minimizing surgical delay is the most important
      factor in reducing mortality in hip fracture patients.

PMID- 23140107
TI  - More accurate component alignment in navigated total knee arthroplasty has no
      clinical benefit at 5-year follow-up.
AB  - BACKGROUND AND PURPOSE: Computer navigation in total knee arthroplasty is
      somewhat controversial. We have previously shown that femoral component
      positioning is more accurate with computed navigation than with conventional
      implantation techniques, but the clinical impact of this is unknown. We now
      report the 5-year outcome of our previously reported 2-year outcome study.
      METHODS: 78 of initially 84 patients (80 of 86 knees) were clinically and
      radiographically reassessed 5 (5.1-5.9) years after conventional, image-based,
      and image-free total knee arthroplasty. The methodology was identical to that
      used preoperatively and at 2 years, including the Knee Society score (KSS) and
      the functional score (FS), and AP and true lateral standard radiographs. RESULTS:
      Although a more accurate femoral component positioning in the navigated groups
      was obtained, clinical outcome, number of reoperations, KSS, FS, and range of
      motion were similar between the groups. INTERPRETATION: The increased costs and
      time for navigated techniques did not translate into better functional and
      subjective medium-term outcome compared to conventional techniques.

PMID- 23140108
TI  - Screening for osteoporosis reduced new fracture incidence by almost half: a 6
      year follow-up of 592 fracture patients from an osteoporosis screening program.
AB  - BACKGROUND AND PURPOSE: Fractures can be prevented if osteoporosis is identified
      and treated. In 2002, we initiated a screening program at our orthopedics
      department, in which patients between 50 and 75 years of age with a wrist,
      shoulder, vertebral, or hip fracture are assessed by DEXA of the hip and spine
      and encouraged to see their doctor for decision on treatment regarding
      osteoporosis. The patients receive written documents containing information, DEXA
      results, and a letter to their doctor with suggestions regarding blood tests and
      treatment. In this 6-year follow-up study, we compared the fracture recurrence in
      2 groups: patients screened for osteoporosis after fracture as described, and a
      historical control group with fracture patients who presented at our department 1
      year before we started the screening intervention. METHODS: A questionnaire was
      sent to the 2 groups of fracture patients, those from before the time that we
      started the screening in 2002 and those who participated in the initial screening
      study in 2003. The questionnaire included questions on whether they had sustained
      further fractures, whether they had seen a doctor, and whether treatment had been
      initiated. RESULTS: 239 of the 306 unscreened patients (68%) and 219 of the 286
      screened patients (77%) answered the questionnaire. In the unscreened group, 69
      new fractures had occurred, in contrast to 39 in the screened group. The fracture
      risk was 42% lower in the screened group. Answers regarding treatment were
      incomplete in the unscreened group. INTERPRETATION: Screening of fracture
      patients for osteoporosis reduced fracture recurrence, which indicates that the
      screening procedure has resulted in treatment that prevents fractures.

PMID- 23140109
TI  - Periprosthetic Vancouver type B1 and C fractures treated by locking-plate
      osteosynthesis: fracture union and reoperations in 60 consecutive fractures.
AB  - BACKGROUND AND PURPOSE: Historically, the treatment of periprosthetic femoral
      fractures (PFFs) has been associated with a high frequency of complications and
      reoperations. The preferred treatment is internal fixation, a revision of the
      femoral stem, or a combination of both. An improved understanding of plate use
      during internal fixation, and the introduction of locking-plate osteosynthesis
      may lead to improved outcome. We evaluated the outcome of Vancouver type B1 and C
      PFFs treated by locking-plate osteosynthesis, by assessing rates of fracture
      union and reoperations and by analyzing failure cases. PATIENTS AND METHODS: From
      2002 through 2011, 58 consecutive patients (60 fractures) with low-energy PFF
      around or below a stable femoral stem, i.e. Vancouver type B1 and C fractures,
      underwent osteosynthesis with a locking plate. All patients had a total hip
      replacement (THR). They were followed up clinically and radiographically, with 6
      weeks between visits, until fracture union or until death. Fracture union was
      evaluated 6 months postoperatively. RESULTS: At a median follow-up time of 23 (0
      121) months after PFF, 8 patients (8 fractures) had been reoperated due either to
      infection (n = 4), failure of fixation (n = 3), or loosening of the femoral stem
      (n = 1). All the patients who had been followed up for at least 6 months-and who
      did not undergo reoperation or die-went on to fracture union (n = 43).
      INTERPRETATION: Locking-plate osteosynthesis of periprosthetic Vancouver type B1
      and C fractures gives good results regarding fracture union. It appears that
      spanning of the prosthesis to avoid stress-rising areas is important for
      successful treatment. Infection is the major cause of failure.

PMID- 23140110
TI  - Development of the Knee Injury and Osteoarthritis Outcome Score for children
      (KOOS-Child): comprehensibility and content validity.
AB  - BACKGROUND AND PURPOSE: The Knee Injury and Osteoarthritis Outcome Score (KOOS)
      is distinguished from other knee-specific measures by the inclusion of separate
      scales for evaluation of activities of daily living, sports and recreation
      function, and knee-related quality of life, with presentation of separate
      subscale scores as a profile. However, its applicability in children has not been
      established. In this study, we examined how well the KOOS could be understood in
      a cohort of children with knee injury, with a view to preparing a pediatric
      version (KOOS-Child). MATERIAL AND METHODS: A trained researcher conducted
      cognitive interviews with 34 Swedish children who had symptomatic knee injuries
      (either primary or repeated). They were 10-16 years of age, and were selected to
      allow for equal group representation of age and sex. All the interviews were
      recorded. 4 researchers analyzed the data and modified the original KOOS
      questionnaire. RESULTS: Many children (n =14) had difficulty in tracking items
      based on the time frame and an equivalent number of children had trouble in
      understanding several terms. Mapping errors resulted from misinterpretation of
      items and from design issues related to the item such as double-barreled format.
      Most children understood how to use the 5-point Likert response scale. Many
      children found the instructions confusing from both a lexical and a formatting
      point of view. Overall, most children found that several items were irrelevant.
      INTERPRETATION: The original KOOS is not well understood by children.
      Modifications related to comprehension, mapping of responses, and jargon in the
      KOOS were made based on qualitative feedback from the children.

PMID- 23140111
TI  - Low-level laser therapy in pediatric Bell's palsy: case report in a three-year
      old child.
AB  - OBJECTIVES: The objective of this study was to apply low-level laser therapy
      (LLLT) to accelerate the recovery process of a child patient with Bell's palsy
      (BP). DESIGN: This was a prospective study. SUBJECT: The subject was a three-year
      old boy with a sudden onset of facial asymmetry due to an unknown cause.
      MATERIALS AND METHODS: The low-level laser source used was a gallium aluminum
      arsenide semiconductor diode laser device (660 nm and 780 nm). No steroids or
      other medications were given to the child. The laser beam with a 0.04-cm(2) spot
      area, and an aperture with approximately 1-mm diameter, was applied in a
      continuous emission mode in direct contact with the facial area. The duration of
      a laser session was between 15 and 30 minutes, depending on the chosen points and
      the area being treated. Light was applied 10 seconds per point on a maximum
      number of 80 points, when the entire affected (right) side of the face was
      irradiated, based on the small laser beam spot size. According to the acupuncture
      literature, this treatment could also be carried out using 10-20 Chinese
      acupuncture points, located unilaterally on the face. In this case study, more
      points were used because the entire affected side of the face (a large area) was
      irradiated instead of using acupuncture points. OUTCOME MEASURES: The House
      Brackmann grading system was used to monitor the evolution of facial nerve motor
      function. Photographs were taken after every session, always using the same
      camera and the same magnitude. The three-year-old boy recovered completely from
      BP after 11 sessions of LLLT. There were 4 sessions a week for the first 2 weeks,
      and the total treatment time was 3 weeks. RESULTS: The result of this study was
      the improvement of facial movement and facial symmetry, with complete
      reestablishment to normality. CONCLUSIONS: LLLT may be an alternative to speed up
      facial normality in pediatric BP.

PMID- 23140112
TI  - Cardiovascular reactivity to and recovery from stressful tasks following a
      mindfulness analog in college students with a family history of hypertension.
AB  - OBJECTIVES: Ninety-seven (97) undergraduates with a family history of
      hypertension participated in a study that evaluated the effects of a brief
      mindfulness-induction on cardiovascular reactivity and recovery to two stressors.
      MATERIALS AND METHODS: Participants were randomized to either a mindfulness
      induction or control condition and were then exposed to the cold pressor task
      (CPT) followed by the mirror-tracing task (MT). Blood pressure and heart rate
      were measured at baseline and postinduction, as well as during and immediately
      following each stressor. RESULTS: There were no group differences in reactivity
      to either stressor. Participants in the mindfulness-analog condition experienced
      significantly greater latency to systolic blood pressure recovery following the
      CPT and a tendency toward greater latency to diastolic blood pressure recovery,
      although these findings were not replicated with the MT task. CONCLUSIONS: These
      results are contrary to what was hypothesized and to the anecdotal evidence
      available regarding effects of comprehensive mindfulness interventions on
      reactivity. The findings are discussed with respect to purported mechanisms of
      mindfulness and learning theory.

PMID- 23140113
TI  - Blinding in clinical trials: a practical approach.
AB  - Blinding is important in the conduct of clinical trials, yet it generally
      receives less attention and effort than other trial components (e.g.,
      randomization, compliance) that are rigorously treated in the design and/or
      analysis stages. Furthermore, although the word "blind" commonly appears in the
      titles of publications, its use is not always well justified. We are human
      beings, and our behavior or decisions can change depending on whether our eyes
      are open or closed. That is why virtually everyone in the clinical trial
      community, including subjects, investigators, treating practitioners, and outcome
      assessors, would agree that some form of blinding is needed to reach a fair and
      objective conclusion uninfluenced by knowledge of intervention assignment.
      Despite our best efforts, however, blinding may not always be successful. There
      is a considerable body of literature about blinding and the need to assess
      whether it has been properly implemented and maintained. By discussing how the
      trialist and the team may handle blinding-related issues in different stages of a
      clinical trial, this brief article intends to offer reasonable suggestions that
      could improve current practice, helping researchers deal confidently with
      blinding-related issues and research in a manner that meets rigorous standards,
      but is practical and flexible.

PMID- 23140114
TI  - Chaoyi Fanhuan Qigong and fibromyalgia: methodological issues and two case
      reports.
AB  - BACKGROUND: Qigong, which has many forms, was recently described as "meditative
      movement," and represents a self-care technique that can contribute to improved
      health. There are challenges involved in research into qigong, including defining
      the amount of instruction required for threshold effects, and whether there is a
      relationship between amount of practice and outcomes. Recent clinical trials
      examining Chaoyi Fanhuan Qigong (CFQ) for fibromyalgia have used a standardized
      regimen of practice over an 8-week period. CASE REPORT: Between a pilot trial and
      a subsequent larger controlled trial, 2 individuals with fibromyalgia of over 20
      years' duration undertook levels 1-4 CFQ training involving movements and
      meditation at a community-based event and then practiced regularly over a 1-year
      period. They subsequently both undertook further training, and consolidated their
      health gains. Both observed major reductions in pain, improvements in sleep,
      mood, emotions, food and other allergies, and consider their condition
      essentially resolved. They have ceased taking several medications and have
      resumed their lives. RESULTS: The information provided by these individuals could
      not be derived from a clinical trial, as it is unlikely people would commit to
      this amount of practice. CONCLUSIONS: The case study approach provides data with
      respect to extent of practice, perseverance and long-term outcomes, and provides
      valuable insight into the potential of this self-care practice.

PMID- 23140115
TI  - Effect of inhaled essential oils on mental exhaustion and moderate burnout: a
      small pilot study.
AB  - OBJECTIVES: The objective of this pilot study was to determine the effectiveness
      of a mixture of essential oils (peppermint, basil, and helichrysum) on mental
      exhaustion, or moderate burnout (ME/MB) using a personal inhaler. DESIGN: This
      was a randomized, controlled, double-blind pilot study. Data were collected 3
      times a day for 3 weeks (Monday-Friday). The first week was baseline for both
      groups, the second week was intervention (aromatherapy or placebo), and the third
      week was washout. SETTINGS/LOCATION: Participants used a personal inhaler at home
      or at work. SUBJECTS: The subjects comprised a convenience sample of 13 women and
      1 man who each had self-assessed ME/MB. INTERVENTIONS: Participants were
      randomized to receive a personal inhaler containing either a mixture of essential
      oils or rose water (as used in Indian cooking). OUTCOME MEASURES: The outcome
      measures were a 0-10 scale with 10=worst feeling of burnout, 0=no feeling of
      burnout. There was a qualitative questionnaire rating aroma and a questionnaire
      listing perceived stressors. RESULTS: While both groups had a reduction in
      perception of ME/MB, the aromatherapy group had a much greater reduction.
      CONCLUSIONS: The results suggest that inhaling essential oils may reduce the
      perceived level of mental fatigue/burnout. Further research is warranted.

PMID- 23140116
TI  - Gender, pride and medical circumcision in contemporary Japan.
AB  - The outcome of interviews with 26 Japanese men is analysed to identify their
      views concerning male circumcision and their implications in terms of embodiment,
      gender and sexuality. Data were collected as part of a larger ethnographic
      investigation of circumcision, masculinity, sexual behaviour and health matters
      for Japanese men. Participants in the investigation offered their views in
      relation to male circumcision by deploying arguments that commodify male
      genitalia and stress masculinity and sexual prowess. Male circumcision was
      thought of as a medical technology oriented towards boosting the gender identity
      of adolescent and/or 'incomplete' men. Male circumcision may also be also
      promoted as a medical strategy to help heterosexual couples conceive. References
      to circumcision as a procedure for disease prevention were almost completely
      absent.

PMID- 23140117
TI  - Special issue in memory of Dr. Stephen F. Lowry.

PMID- 23140118
TI  - In memoriam: Stephen F. Lowry, MD, MBA.

PMID- 23140120
TI  - Toward prediction of immune mechanisms and design of immunotherapies in melanoma.
AB  - Malignant melanoma, the most lethal skin cancer, is considered as a
      representative model for cross talk between immune responses and malignancy.
      Efforts to elucidate the nature of these interactions have translated into
      immunotherapeutic strategies. Adjuvant therapeutics such as IL-2 and IFNalpha2b
      have reached clinical application, and emerging therapies targeting key
      immunomodulatory molecules such as CTLA-4 have renewed excitement in the field,
      highlighting the potential of manipulating immune responses in the clinical
      setting, but also the merits for further elucidating complex underlying
      immunological pathways. Screening technologies have yielded new insights leading
      to identification of biomarkers for disease prognosis and applied clinical
      immunotherapies. The promise of systems biology is to integrate diverse
      biomedical characterizations into detailed models of underlying mechanisms and
      therapies through suitable computational and mathematical formalisms. In this
      review, we discuss recent developments in dissecting the complex and diverse
      immune responses associated with melanoma through both computational and
      experimental means. We show the significance of devising new, improved approaches
      that can better serve as models of immune interactions and therapies. We propose
      that efforts in this direction may realize the potential of personalized medicine
      and facilitate development of the next generation of efficacious tools to treat
      patients.

PMID- 23140119
TI  - Molecular mechanisms of chronic intermittent hypoxia and hypertension.
AB  - Obstructive sleep apnea (OSA) is characterized by episodes of repeated airway
      obstruction resulting in cessation (apnea) or reduction (hypopnea) in airflow
      during sleep. These events lead to intermittent hypoxia and hypercapnia, sleep
      fragmentation, and changes in intrathoracic pressure, and are associated with a
      marked surge in sympathetic activity and an abrupt increase in blood pressure.
      Blood pressure remains elevated during wakefulness despite the absence of
      obstructive events resulting in a high prevalence of hypertension in patients
      with OSA. There is substantial evidence that suggests that chronic intermittent
      hypoxia (CIH) leads to sustained sympathoexcitation during the day and changes in
      vasculature resulting in hypertension in patients with OSA. Mechanisms of
      sympathoexcitation include augmentation of peripheral chemoreflex sensitivity and
      a direct effect on central sites of sympathetic regulation. Interestingly, the
      vascular changes that occur with CIH have been ascribed to the same molecules
      that have been implicated in the augmented sympathetic tone in CIH. This review
      will discuss the hypothesized molecular mechanisms involved in the development of
      hypertension with CIH, will build a conceptual model for the development of
      hypertension following CIH, and will propose a systems biology approach in
      further elucidating the relationship between CIH and the development of
      hypertension.

PMID- 23140123
TI  - Addressing the translational dilemma: dynamic knowledge representation of
      inflammation using agent-based modeling.
AB  - Given the panoply of system-level diseases that result from disordered
      inflammation, such as sepsis, atherosclerosis, cancer, and autoimmune disorders,
      understanding and characterizing the inflammatory response is a key target of
      biomedical research. Untangling the complex behavioral configurations associated
      with a process as ubiquitous as inflammation represents a prototype of the
      translational dilemma: the ability to translate mechanistic knowledge into
      effective therapeutics. A critical failure point in the current research
      environment is a throughput bottleneck at the level of evaluating hypotheses of
      mechanistic causality; these hypotheses represent the key step toward the
      application of knowledge for therapy development and design. Addressing the
      translational dilemma will require utilizing the ever-increasing power of
      computers and computational modeling to increase the efficiency of the scientific
      method in the identification and evaluation of hypotheses of mechanistic
      causality. More specifically, development needs to focus on facilitating the
      ability of non-computer trained biomedical researchers to utilize and instantiate
      their knowledge in dynamic computational models. This is termed "dynamic
      knowledge representation." Agent-based modeling is an object-oriented, discrete
      event, rule-based simulation method that is well suited for biomedical dynamic
      knowledge representation. Agent-based modeling has been used in the study of
      inflammation at multiple scales. The ability of agent-based modeling to encompass
      multiple scales of biological process as well as spatial considerations, coupled
      with an intuitive modeling paradigm, suggest that this modeling framework is well
      suited for addressing the translational dilemma. This review describes agent
      based modeling, gives examples of its applications in the study of inflammation,
      and introduces a proposed general expansion of the use of modeling and simulation
      to augment the generation and evaluation of knowledge by the biomedical research
      community at large.

PMID- 23140121
TI  - Pharmacokinetic/pharmacodynamic modeling in inflammation.
AB  - Inflammation is an array of immune responses to infection and injury. It results
      from a complex immune cascade and is the basis of many chronic diseases such as
      arthritis, diabetes, and cancer. Numerous mathematical models have been developed
      to describe the disease progression and effects of anti-inflammatory drugs. This
      review illustrates the state of the art in modeling the effects of diverse drugs
      for treating inflammation, describes relevant biomarkers amenable to modeling,
      and summarizes major advantages and limitations of the published pharmacokinetic/
      pharmacodynamic (PK/PD) models. Simple direct inhibitory models are often used to
      describe in vitro effects of anti-inflammatory drugs. Indirect response models
      are more mechanism based and have been widely applied to the turnover of symptoms
      and biomarkers. These, along with target-mediated and transduction models, have
      been successfully applied to capture the PK/PD of many anti-inflammatory drugs
      and describe disease progression of inflammation. Biologics have offered
      opportunities to address specific mechanisms of action, and evolve small systems
      models to quantitatively capture the underlying physiological processes. More
      advanced mechanistic models should allow evaluation of the roles of some key
      mediators in disease progression, assess drug interactions, and better translate
      drug properties from in vitro and animal data to patients.

PMID- 23140122
TI  - Modeling physiologic variability in human endotoxemia.
AB  - The control and management of inflammation is a key aspect of clinical care for
      critical illnesses such as sepsis. In an ideal reaction to injury, the
      inflammatory response provokes a strong enough response to heal the injury and
      then restores homeostasis. When inflammation becomes dysregulated, a persistent
      inflammatory state can lead to significant deleterious effects and clinical
      challenges. Thus, gaining a better biological understanding of the mechanisms
      driving the inflammatory response is of the utmost importance. In this review, we
      discuss our work with the late Stephen F. Lowry to investigate systemic
      inflammation through systems biology of human endotoxemia. We present our efforts
      in modeling the human endotoxemia response with a particular focus on physiologic
      variability. Through modeling, with a focus ultimately on translational
      applications, we obtain more fundamental understanding of relevant physiological
      processes. And by taking advantage of the information embedded in biological
      rhythms, ranging in time scale from high-frequency autonomic oscillations
      reflected in heart rate variability to circadian rhythms in inflammatory
      mediators, we gain insight into the underlying physiology.

PMID- 23140125
TI  - Sepsis through the eyes of an engineer -- why treatments have succeeded and
      failed.
AB  - The sepsis syndrome is an old phenomenon. A destructive response to a system
      disturbance, it manifests as widespread inflammation. Over the past two
      centuries, biomedical research has identified triggers and described components
      of the pathways that underlie the sepsis syndrome. Attempts at translating these
      findings into preventive and therapeutic interventions have met with varying
      levels of success. In this chapter, we examine the history of sepsis science
      through an engineering lens. Patterned attempts to intervene in the natural
      history of the sepsis syndrome will be discussed in parallel with similar,
      hypothetical adjustments made to a model system from the engineering canon. This
      juxtaposition will facilitate our review of the history of sepsis science. Using
      the logic of systems engineering and network science, we propose a way forward.

PMID- 23140126
TI  - Use of prone position magnetic resonance imaging for detecting the terminal filum
      in patients with occult tethered cord syndrome.
AB  - OBJECT: The pathophysiology of occult tethered cord syndrome (OTCS) with no
      anatomical evidence of a caudally shifted conus and a normal terminal filum is
      hard to understand. Therefore, the diagnosis of OTCS is often difficult. The
      authors hypothesized that the posterior displacement of the terminal filum may
      become prominent in patients with OCTS who are in a prone position if filum
      inelasticity exists, and they investigated prone-position MRI findings. METHODS:
      Fourteen patients with OTCS and 12 control individuals were examined using T2
      weighted axial MRI with the patients in a prone position on a flat table. On each
      axial view, the distance between the posterior and anterior ends of the
      subarachnoid space (A), the distance between the posterior end of the
      subarachnoid space and the terminal filum (B), the distance between the posterior
      end of the subarachnoid space and the dorsal-most nerve among the cauda equina
      (C), and the distance between the posterior end of the subarachnoid space and the
      ventral-most nerve (D) were measured. The location ratios of the terminal filum,
      the dorsal-most nerve, and the ventral-most nerve were calculated by the ratio of
      A to B (defined as TF = B/A), A to C (defined as DN = C/A), and A to D (defined
      as VN = D/A), respectively. Patients underwent sectioning of the terminal filum
      with the aid of a surgical microscope. The low-back pain Japanese Orthopaedic
      Association score was obtained before surgery and at the final follow-up visit.
      RESULTS: On prone-position axial MRI, the terminal filum was separated from the
      cauda equina and was shifted caudally to posterior in the subarachnoid space in
      all patients with OTCS. The locations of the caudal cauda equina shifted to
      ventral in the subarachnoid space. The TF values in the OTCS group were
      significantly lower than those in the control group at the L3-4 (p = 0.023), L-4
      (p = 0.030), L4-5 (p = 0.002), and L-5 (p < 0.001) levels. In contrast, the DN
      values in the OTCS group were significantly higher than those of the control
      group at the L-2 (p = 0.003), L2-3 (p = 0.002), L-3 (p < 0.001), L3-4 (p <
      0.001), L-4 (p = 0.007), L4-5 (p = 0.003), and S-1 (p = 0.014) levels, and the VN
      values in the OTCS group were also significantly higher than those of the control
      group at the L2-3 (p = 0.022), L-3 (p = 0.027), L3-4 (p = 0.002), L-4 (p =
      0.011), L4-5 (p = 0.019), and L5-S1 (p = 0.040) levels. Sections were collected
      during surgery for histological evaluation, and a decreased elasticity within the
      terminal filum was suggested. Improvements in the Japanese Orthopaedic
      Association score were observed at the final follow-up in all patients.
      CONCLUSIONS: The authors' new method of using the prone position for MRI shows
      that the terminal filum is located significantly posterior and the cauda equina
      is located anterior in patients with OTCS, suggesting a difference in elasticity
      between the terminal filum and cauda equina.

PMID- 23140124
TI  - Sepsis: from pattern to mechanism and back.
AB  - Sepsis is a clinical entity in which complex inflammatory and physiological
      processes are mobilized, not only across a range of cellular and molecular
      interactions, but also in clinically relevant physiological signals accessible at
      the bedside. There is a need for a mechanistic understanding that links the
      clinical phenomenon of physiologic variability with the underlying patterns of
      the biology of inflammation, and we assert that this can be facilitated through
      the use of dynamic mathematical and computational modeling. An iterative approach
      of laboratory experimentation and mathematical/computational modeling has the
      potential to integrate cellular biology, physiology, control theory, and systems
      engineering across biological scales, yielding insights into the control
      structures that govern mechanisms by which phenomena, detected as biological
      patterns, are produced. This approach can represent hypotheses in the formal
      language of mathematics and computation, and link behaviors that cross scales and
      domains, thereby offering the opportunity to better explain, diagnose, and
      intervene in the care of the septic patient.

PMID- 23140127
TI  - Posterior dynamic stabilization in the treatment of degenerative lumbar stenosis:
      validity of its rationale.
AB  - OBJECT: The authors undertook this study to investigate the validity of the
      rationale for posterior dynamic stabilization using the Device for Intervertebral
      Assisted Motion (DIAM) in the treatment of degenerative lumbar stenosis. METHODS:
      A cohort of 31 patients who underwent single-level decompression and DIAM
      placement for degenerative lumbar stenosis were followed up for at least 2 years
      and data pertaining to their cases were analyzed prospectively. Of these
      patients, 7 had retrolisthesis. Preoperative and postoperative plain lumbar
      radiographs obtained in all patients and CT images obtained in 14 patients were
      analyzed. Posterior disc heights; range of motion (ROM) of proximal, distal, and
      implant segments; lordotic angles of implant segments; percentage of
      retrolisthesis; and cross-sectional area and heights of intervertebral foramina
      on CT sagittal images were analyzed. Clinical outcomes were evaluated using
      visual analog scale scores and Oswestry Disability Index scores. RESULTS: The
      mean values for posterior disc height before surgery, at 1 week after surgery,
      and at the final follow-up visits were 6.4 +/- 2.0 mm, 9.7 +/- 2.8 mm, and 6.8 +/
      2.5 mm, respectively. The mean lordotic angles at the implant levels before
      surgery, at 1 week after surgery, and at the final follow-up visits were 7.1
      degrees  +/- 3.3 degrees , 4.1 degrees  +/- 2.7 degrees , and 7.0 degrees  +/-
      3.7 degrees , respectively. No statistically significant difference was found
      between the preoperative values and values from final follow-up visits for
      posterior disc height and lordotic angles at implant levels (p = 0.17 and p =
      0.10, respectively). There was no statistically significant difference between
      the preoperative and final follow-up visit values for intervertebral foramen
      cross-sectional area and heights on CT images. The ROMs of proximal and distal
      segments also showed no significant decrease (p = 0.98 and p = 0.92,
      respectively). However, the ROMs of implant segments decreased significantly (p =
      0.02). The average 31.4-month improvement for all clinical outcome measures was
      significant (p < 0.001). CONCLUSIONS: Based on radiological findings, the DIAM
      failed to show validity in terms of the rationale of indirect decompression, but
      it did restrict motion at the instrumented level without significant change in
      adjacent-segment ROM. The clinical condition of the patients, however, was
      improved, and improvement was maintained despite progressive loss of posterior
      disc height after surgery.

PMID- 23140128
TI  - Prospective study of disc repair with allogeneic chondrocytes presented at the
      2012 Joint Spine Section Meeting.
AB  - OBJECT: The purpose of the study was to evaluate the safety and initial efficacy
      of NuQu allogeneic juvenile chondrocytes delivered percutaneously for the
      treatment of lumbar spondylosis with mechanical low-back pain (LBP). NuQu is a
      cell-based biological therapy for disc repair. The authors report the results at
      12 months of the NuQu Phase I investigational new drug (IND) single-arm,
      prospective feasibility study for the treatment of LBP for single-level
      degenerative disc disease (Pfirrman Grades III-IV) at L3-S1. METHODS: Fifteen
      patients (6 women and 9 men) were enrolled at 2 sites. Institutional review board
      approval was obtained, and all patients signed a study-specific informed consent.
      All patients have completed a minimum of 1 year of follow-up. Patients were
      evaluated pretreatment and at 1, 3, 6, and 12 months posttreatment. Evaluations
      included routine neurological examinations, serum liver and renal function
      studies, MRI, the Oswestry Disability Index (ODI), the Numerical Rating Scale
      (NRS), and the 36-Item Short Form Health Survey (SF-36). RESULTS: Fifteen
      patients were treated with a single percutaneous delivery of NuQu juvenile
      chondrocytes. The mean patient age was 40 years (19-47 years). Each treatment
      consisted of 1-2 ml (mean injection 1.3 ml) of juvenile chondrocytes
      (approximately 10(7) chondrocyte cells/ml) with fibrin carrier. The mean peak
      pressure during treatment was 87.6 psi. The treatment time ranged from 5 to 33
      seconds. The mean ODI (baseline 53.3, 12-month 20.3; p < 0.0001), NRS (baseline
      5.7, 12-month 3.1; p = 0.0025), and SF-36 physical component summary (baseline
      35.3, 12-month 46.9; p = 0.0002) scores all improved significantly from baseline.
      At the 6-month follow-up, 13 patients underwent MRI (one patient underwent CT
      imaging and another refused imaging). Ten (77%) of these 13 patients exhibited
      improvements on MRI. Three of these patients showed improvement in disc contour
      or height. High-intensity zones (HIZs), consistent with posterior anular tears,
      were present at baseline in 9 patients. Of these, the HIZ was either absent or
      improved in 8 patients (89%) by 6 months. The HIZ was improved in the ninth
      patient at 3 months, with no further MRI follow-up. Of the 10 patients who
      exhibited radiological improvement at 6 months, findings continued to improve or
      were sustained in 8 patients at the 12-month follow-up. No patient experienced
      neurological deterioration. There were no disc infections, and there were no
      serious or unexpected adverse events. Three patients (20%) underwent total disc
      replacement by the 12-month follow-up due to persistent, but not worse than
      baseline, LBP. CONCLUSIONS: This is a 12-month report of the clinical and
      radiographic results from a US IND study of cell-based therapy (juvenile
      chondrocytes) in the treatment of lumbar spondylosis with mechanical LBP. The
      results of this prospective cohort are promising and warrant further
      investigation with a prospective, randomized, double-blinded, placebo-controlled
      study design. Clinical trial registration no.: BB-IND 13985.

PMID- 23140129
TI  - Prospective randomized study of cervical arthroplasty and anterior cervical
      discectomy and fusion with long-term follow-up: results in 74 patients from a
      single site.
AB  - OBJECT: The purpose of this study was to evaluate the long-term results of
      cervical total disc replacement (TDR) and anterior cervical discectomy and fusion
      (ACDF) in the treatment of single-level cervical radiculopathy. METHODS: The
      results of 2 separate prospective, randomized, US FDA Investigational Device
      Exemption pivotal trials (Bryan Disc and Kineflex|C) from a single
      investigational site were combined to evaluate outcomes at long-term follow-up.
      The primary clinical outcome measures included the Neck Disability Index (NDI),
      visual analog scale (VAS), and neurological examination. Patients were randomized
      to receive cervical TDR in 2 separate prospective, randomized studies using the
      Bryan Disc or Kineflex|C cervical artificial disc compared with ACDF using
      structural allograft and an anterior plate. Patients were evaluated
      preoperatively; at 6 weeks; at 3, 6, and 12 months; and then yearly for a minimum
      of 48 months. Plain radiographs were obtained at each study visit. RESULTS: A
      total of 74 patients were enrolled and randomly assigned to either the cervical
      TDR (n = 41) or ACDF (n = 33) group. A total of 63 patients (86%) completed a
      minimum of 4 years follow-up. Average follow-up was 6 years (72 months) with a
      range from 48 to 108 months. In both the cervical TDR and ACDF groups, mean NDI
      scores improved significantly by 6 weeks after surgery and remained significantly
      improved throughout the minimum 48-month follow-up (p < 0.001). Similarly, the
      median VAS pain scores improved significantly by 6 weeks and remained
      significantly improved throughout the minimum 48-month follow-up (p < 0.001).
      There were no significant differences between groups in mean NDI or median VAS
      scores. The range of motion (ROM) in the cervical TDR group remained
      significantly greater than the preoperative mean, whereas the ROM in the ACDF
      group was significantly reduced from the preoperative mean. There was
      significantly greater ROM in the cervical TDR group compared with the ACDF group.
      There were 3 reoperations (7.3%) at index or adjacent levels in the cervical TDR
      group; all were cervical laminoforaminotomies. There were 2 adjacent-level
      reoperations in the cervical TDR group (4.9%). There was 1 reoperation (3.0%) in
      the ACDF group at an index or adjacent level (a second ACDF at the adjacent
      level). There was no statistically significant difference in overall reoperation
      rate or adjacent-level reoperation rate between groups. CONCLUSIONS: Both
      cervical TDR and ACDF groups showed excellent clinical outcomes that were
      maintained over long-term follow-up. Both groups showed low index-level and
      adjacent-level reoperation rates. Both cervical TDR and ACDF appear to be viable
      options for the treatment of single-level cervical radiculopathy.

PMID- 23140130
TI  - Minimally invasive treatment of multilevel spinal epidural abscess.
AB  - The use of minimally invasive tubular retractor microsurgery for treatment of
      multilevel spinal epidural abscess is described. This technique was used in 3
      cases, and excellent results were achieved. The authors conclude that multilevel
      spinal epidural abscesses can be safely and effectively managed using
      microsurgery via a minimally invasive tubular retractor system.

PMID- 23140131
TI  - Iliac crest osteotomy to enhance exposure of the L4-5 interspace in minimally
      invasive lateral transpsoas interbody fusion: a cadaveric feasibility study.
AB  - OBJECT: Minimally invasive lateral transpsoas interbody fusion (LTIF) has emerged
      as a popular surgical technique in a remarkably short period of time. The
      authors' experience with this procedure and anecdotal evidence in the literature
      suggest that the iliac crest may occasionally prevent access to the L4-5
      interspace during minimally invasive LTIF. The authors propose that removal of a
      minimal amount of ilium would allow for successful exposure of the L4-5
      interspace in those cases with a "high-riding" iliac crest. Therefore, the
      objective of this study was to evaluate the feasibility of iliac osteotomy to
      enhance exposure of the L4-5 interspace for minimally invasive LTIF. METHODS:
      Twenty L4-5 minimally invasive LTIF procedures were performed on 10 cadavers. The
      L4-5 minimally invasive LTIFs were successfully completed in 13 of 20 attempts.
      In the remaining 7 cases, the iliac crest prevented perfect orthogonal access to
      the L4-5 interspace. An iliac osteotomy was performed until the tubular
      retractors could be perfectly aligned with the L4-5 interspace and minimally
      invasive LTIF accomplished. Anteroposterior fluoroscopic images were obtained
      before and after the osteotomies. The angle between the working instrument and
      the superior L-5 endplate was measured, as were craniocaudal displacement and the
      resected iliac area. RESULTS: Iliac osteotomy enabled completion of L4-5
      minimally invasive LTIF in the 7 remaining cases. Iliac resection was minimal; an
      average of 4.92 cm(2) of iliac surface was resected (range 2.08-8.27 cm(2)) to
      enable L4-5 access. Adequate working angles were maintained (average 3.3 degrees 
      change after resection) while significant caudal displacement of the tubular
      system was achieved (average 15.7 mm, range 5.2-27.6 mm). CONCLUSIONS: A
      significant portion of patients may have a high-riding iliac crest and that may
      have had an impact on minimally invasive LTIF in this series; L4-5 cases are rare
      in relation to midlumbar spine cases in most minimally invasive LTIF patient
      series. Significant caudal displacement of the tubular system was achieved with
      minimal iliac osteotomy, ensuring access to the L4-5 interspace in all specimens
      while maintaining the minimally invasive philosophy behind minimally invasive
      LTIF.

PMID- 23140132
TI  - The effects of green tea consumption and resistance training on body composition
      and resting metabolic rate in overweight or obese women.
AB  - Green tea has been shown to have thermogenic and antiobesity properties.
      Therefore, it is important to investigate its effect on weight loss in humans,
      especially in women. We investigated the effects of green tea consumption
      combined with resistance training on the body composition and the resting
      metabolic rate (RMR) in women who were overweight or obese (grade I). After 4
      weeks on an adaptive diet, 36 women were divided into four groups (group 1 green
      tea; group 2 placebo; group 3 green tea plus resistance training; group 4 placebo
      plus resistance training). The study was double-blinded and placebo-controlled.
      The RMR and body composition were ascertained for each volunteer, blood tests
      were performed, and subjects in groups 3 and 4 were tested for their one
      repetition maximum. Each subject followed the protocol and continued the diet for
      eight additional weeks, and periodic evaluations were administered. The mean RMR
      of group 1 decreased significantly and was accompanied by weight loss,
      maintenance of lean body mass, and decreases in both waist circumference and body
      mass index. Group 2 showed no variations in anthropometric or blood variables and
      significantly decreased their mean RMR. Group 3 showed significant increases in
      RMR, lean body mass, and muscle strength, and significant decreases in body fat,
      triglycerides, and waist circumference as compared to group 4. Green tea combined
      with resistance training its potential is increased with decreasing body fat,
      waist circumference, and triacylglyceride levels and by increasing lean body mass
      and muscle strength.

PMID- 23140134
TI  - Early versus conventional switching of antidepressant: a post-hoc analysis of
      clinical trial data for major depressive disorder with moderate to severe pain
      symptoms.
AB  - A number of different antidepressants, each with unique pharmacological profiles,
      are used for treatment of major depressive disorder (MDD); however, these drugs
      have been found in placebo-controlled, large practical clinical trials to have
      limited efficacy for achieving full recovery in MDD patients. In particular, when
      depressed patients have pain symptoms, their chance of remission is significantly
      decreased. Pain also often leads to residual symptoms and incomplete functional
      recovery. Hence, while pain should be a principal target symptom in patients with
      MDD, there continues to be unmet need for pain treatment in depressed patients.
      Therefore, more diverse options for treatment approaches can be expected to
      enhance outcomes in clinical treatment of depressed patients with comorbid pain.
      In this context, Dr. Romera and colleagues have investigated an early
      antidepressant-switching strategy in patients with initial treatment failure.
      They found that early switching to a different antidepressant in MDD patients
      with moderate-to-severe symptoms of physical pain seems to lead to better pain
      and functional outcomes. This article discusses clinical significance, practical
      issues, potential limitations, and future research implications based on the
      findings from Dr. Romera and colleagues' study.

PMID- 23140133
TI  - Rfa2 is specifically dephosphorylated by Pph3 in Candida albicans.
AB  - Rfa2 is a ssDNA (single-stranded DNA)-binding protein that plays an important
      role in DNA replication, recombination and repair. Rfa2 is regulated by
      phosphorylation, which alters its protein-protein interaction and protein-DNA
      interaction. In the present study, we found that the Pph3-Psy2 phosphatase
      complex is responsible for Rfa2 dephosphorylation both during normal G1-phase and
      under DNA replication stress in Candida albicans. Phosphorylated Rfa2 extracted
      from pph3Delta or psy2Delta G1 cells exhibited diminished binding affinity to
      dsDNA (double-stranded DNA) but not to ssDNA. We also discovered that Cdc28 (cell
      division cycle 28) and Mec1 are responsible for Rfa2 phosphorylation in G1-phase
      and under DNA replication stress respectively. Moreover, MS revealed that the
      domain of Rfa2 that was phosphorylated in G1-phase differed from that
      phosphorylated under the stress conditions. The results of the present study
      imply that differential phosphorylation plays a crucial role in RPA (replication
      protein A) regulation.

PMID- 23140135
TI  - Dual-signal amplification strategy for ultrasensitive photoelectrochemical
      immunosensing of alpha-fetoprotein.
AB  - An ultrasensitive photoelectrochemical immunoassay of cancer biomarker alpha
      fetoprotein (AFP) is proposed that uses titanium dioxide (TiO(2)) coupled with
      AFP-CdTe-GOx bioconjugate, which featured AFP antigen and glucose oxidase (GOx)
      labels linked to CdTe quantum dots (QDs) for signal amplification. The
      synthesized CdTe QDs yielded a homogeneous and narrow size distribution, which
      allowed the binding of AFP and GOx on CdTe QDs. Greatly enhanced sensitivity for
      AFP came from a dual signal amplification strategy. First, an effective matching
      of energy levels between the conduction bands of CdTe QDs and TiO(2) allowed for
      fast electron injection from excited CdTe QDs to TiO(2) upon irradiation, which
      reduced the recombination process of electron-hole pairs and prompted
      photoelectrochemical performance. Second, GOx enzyme could catalyze glucose to
      produce H(2)O(2), which acted as a sacrificial electron donor to scavenge the
      photogenerated holes in the valence band of CdTe QDs, further causing an enhanced
      photocurrent. Thus, on the basis of the dual signal amplification strategy, the
      competitive immunosensor based on the specific binding of anti-AFP antibodies to
      AFP and AFP-CdTe-GOx bioconjugates was achieved. This proposed biosensor for AFP
      possessed largely increased linear detection range from 0.5 pg/mL to 10 MUg/mL
      with a detection limit of 0.13 pg/mL. The proposed amplification strategy shows
      high sensitivity, stability, and reproducibility and can become a promising
      platform for other protein detection.

PMID- 23140137
TI  - Photoelectron spectroscopy and computational modeling of thymidine homodimer
      anions.
AB  - The intact thymidine homodimer anion (dT(2)(-)) was generated in the gas phase
      using an infrared desorption/photoemission source and recorded by a pulsed
      photoelectron spectrometer. The photoelectron spectrum (PES) revealed a broad
      signal with the maximum at electron binding energy ~2.0 eV and the threshold
      value at 1.1 eV. The relative energies and vertical detachment energies of the
      possible anion structures were calculated at the B3LYP/6-31++G(d,p) level. Here
      we report that the most stable anion radical homodimer geometries observed in the
      PES are the anionic nucleoside coordinated by the O8 atom of thymine to the
      deoxyribose of the second neutral nucleoside. Unlike previous experimental
      computational studies on anionic complexes involving nucleobases with proton
      donors, the electron-induced proton-transferred structures are not responsible
      for the shape of the PES of dT(2)(-).

PMID- 23140136
TI  - Comparative analysis of four oxidized guanine lesions from reactions of DNA with
      peroxynitrite, singlet oxygen, and gamma-radiation.
AB  - Oxidative damage to DNA has many origins, including irradiation, inflammation,
      and oxidative stress, but the chemistries are not the same. The most oxidizable
      base in DNA is 2-deoxyguanosine (dG), and the primary oxidation products are 8
      oxodG and 2-amino-imidazolone. The latter rapidly converts to 2,2-diamino
      oxazolone (Ox), and 8-oxodG is further oxidized to spiroiminodihydantoin (Sp) and
      guanidinohydantoin (Gh). In this study, we have examined the dose-response
      relationship for the formation of the above four products arising in calf thymus
      DNA exposed to gamma irradiation, photoactivated rose bengal, and two sources of
      peroxynitrite. In order to carry out these experiments, we developed a
      chromatographic system and synthesized isotopomeric internal standards to enable
      accurate and precise analysis based upon selected reaction monitoring mass
      spectrometry. 8-OxodG was the most abundant products in all cases, but its
      accumulation was highly dependent on the nature of the oxidizing agent and the
      subsequent conversion to Sp and Gh. Among the other oxidation products, Ox was
      the most abundant, and Sp was formed in significantly greater yield than Gh.

PMID- 23140138
TI  - Tetrathiafulvalene hetero radical cation dimerization in a redox-active
      [2]catenane.
AB  - The electronic properties of tetrathiafulvalene (TTF) can be tuned by attaching
      electron-donating or electron-withdrawing substituents. An electron-rich
      macrocyclic polyether containing two TTF units of different constitutions, namely
      4,4'-bis(hydroxymethyl)tetrathiafulvalene (OTTFO) and 4,4'
      bisthiotetrathiafulvalene (STTFS), has been synthesized. On two-electron
      oxidation, a hetero radical dimer is formed between OTTFO(*+) and STTFS(*+). The
      redox behavior of the macrocyclic polyether has been investigated by
      electrochemical techniques and UV-vis and electron paramagnetic resonance (EPR)
      spectroscopies. The [2]catenane in which the macrocyclic polyether is
      mechanically interlocked with the cyclobis(paraquat-p-phenylene) (CBPQT(4+)) ring
      has also been prepared using template-directed protocols. In the case of the
      [2]catenane, the formation of the TTF hetero radical dimer is prevented
      sterically by the CBPQT(4+) ring. After a one-electron oxidation, a 70:30 ratio
      of OTTFO(*+) to STTFS(*+) is present at equilibrium, and, as a result, two
      translational isomers of the [2]catenane associated with these electronically
      different isomeric states transpire. EPR titration spectroscopy and simulations
      reveal that the radical states of the two constitutionally different TTF units in
      the [2]catenane still experience long-range electronic intramolecular coupling
      interactions, despite the presence of the CBPQT(4+) ring, when one or both of
      them are oxidized to the radical cationic state. These findings in the case of
      both the free macrocyclic polyether and the [2]catenane have led to a deeper
      fundamental understanding of the mechanism of radical cation dimer formation
      between constitutionally different TTF units.

PMID- 23140139
TI  - Scanning electron microscope appearances of fretting in the fixed orthodontic
      appliances.
AB  - Fretting is one of the types of a tribologic wear. It is a process that occurs at
      a nominally immovable junction of elements. In dentistry, such elements can be
      brackets and archwires of fixed orthodontic appliances. They meet all the
      criteria for fretting to occur, i.e., they are nominally immovable, are subjected
      to initial loadings and they work in aggressive environment. Chrome-nickel
      stainless steel Elite Opti-Mim brackets (Trachem) working in vivo in oral cavity
      environment in combination with NiTi and stainless steel archwires were
      investigated. Scanning electron micrographs of bracket's working surfaces showed
      the presence of fretting damaged areas. This research also confirmed that there
      were almost all the types of fretting wear on the elements of the orthodontic
      appliances under examination.

PMID- 23140140
TI  - Effects of shutter transients in molecular beam epitaxy.
AB  - : We have studied the effects of shutter transients (STs) in molecular beam
      epitaxy (MBE). Two series of samples were grown by MBE and evaluated by X-ray
      diffraction (XRD) and X-ray reflectivity (XRR) measurements. The effects of STs
      were evaluated by growth rate (GR) analysis using a combination of growth time
      (GT) and thickness evaluated by XRD and XRR measurements. We revealed two
      opposite effects of STs: (1) overshoot of GR and (2) increase in GR with GT and
      subsequent saturation. Each effect was consistent with the previous studies;
      however, the previous studies showed no relationships between these two effects.
      By considering closing time of the shutter, the two opposite effects were well
      understood.

PMID- 23140141
TI  - Evaluation of urinary catheters coated with sustained-release varnish of
      chlorhexidine in mitigating biofilm formation on urinary catheters in dogs.
AB  - BACKGROUND: Biofilm formation occurs commonly on urinary catheters. OBJECTIVES:
      To assess the efficacy of urinary catheters coated with sustained-release varnish
      of chlorhexidine in decreasing catheter-associated biofilm formation in dogs.
      ANIMALS: Thirty client-owned dogs. METHODS: Prospective study. Thirteen dogs were
      catheterized with urinary catheters coated with sustained-release varnish of
      chlorhexidine (study group), and 13 dogs were catheterized with an untreated
      urinary catheter (control group). Presence and intensity of biofilm formation on
      the urinary catheters were assessed and compared between the groups by evaluating
      colony-forming units (CFU) of biofilm bacteria, and semiquantitatively, using
      confocal laser scanning microscopy and electron microscopy. RESULTS: None of the
      dogs experienced adverse effects associated with the presence of the urinary
      catheters. Median CFU count of biofilm bacteria at all portions of the urinary
      catheter was significantly (P < .001) lower in the study compared with the
      control group. The degree of biofilm formation on the urinary catheters, as
      evaluated by confocal laser scanning microscopy and electron microscopy, was
      significantly lower in the study compared with the control group. Electron
      microscopy examination identified crystals on some of the urinary catheters. The
      proportion of catheters on which crystals were observed was significantly lower
      on the distal part of the urinary catheter in the study group compared with the
      control group (16.7% versus 66.7%, respectively; P = .04). CONCLUSIONS AND
      CLINICAL IMPORTANCE: Chlorhexidine sustained-release varnish-coated urinary
      catheters effectively decrease urinary catheter-associated biofilm formation in
      dogs.

PMID- 23140143
TI  - Integrating palliative care within acute stroke services: developing a programme
      theory of patient and family needs, preferences and staff perspectives.
AB  - BACKGROUND: Palliative care should be integrated early into the care
      trajectories of people with life threatening illness such as stroke. However
      published guidance focuses primarily on the end of life, and there is a gap in
      the evidence about how the palliative care needs of acute stroke patients and
      families should be addressed. Synthesising data across a programme of related
      studies, this paper presents an explanatory framework for the integration of
      palliative and acute stroke care. METHODS: Data from a survey (n=191) of patient
      reported palliative care needs and interviews (n=53) exploring experiences with
      patients and family members were explored in group interviews with 29 staff from
      3 United Kingdom stroke services. A realist approach to theory building was used,
      constructed around the mechanisms that characterise integration, their impacts,
      and mediating, contextual influences. RESULTS: The framework includes two
      cognitive mechanisms (the legitimacy of palliative care and individual capacity),
      and behavioural mechanisms (engaging with family; the timing of intervention;
      working with complexity; and the recognition of dying) through which staff
      integrate palliative and stroke care. A range of clinical (whether patients are
      being 'actively treated', and prognostic uncertainty) and service (leadership,
      specialty status and neurological focus) factors appear to influence how
      palliative care needs are attended to. CONCLUSIONS: Our framework is the first,
      empirical explanation of the integration of palliative and acute stroke care. The
      specification in the framework of factors that mediate integration can inform
      service development to improve the outcomes and experiences of patients and
      families.

PMID- 23140142
TI  - Developmental prosopagnosia in childhood.
AB  - Developmental prosopagnosia (DP) is defined by severe face recognition problems
      resulting from a failure to develop the necessary visual mechanisms for
      processing faces. While there is a growing literature on DP in adults, little has
      been done to study this disorder in children. The profound impact of abnormal
      face perception on social functioning and the general lack of awareness of
      childhood DP can result in severe social and psychological consequences for
      children. This review discusses possible aetiologies of DP and summarizes the few
      cases of childhood DP that have been reported. It also outlines key objectives
      for the growth of this emerging research area and special considerations for
      studying DP in children. With clear goals and concerted efforts, the study of DP
      in childhood will be an exciting avenue for enhancing our understanding of normal
      and abnormal face perception for all age groups.

PMID- 23140145
TI  - Quantitative verification of the keyhole concept: a comparison of area of
      exposure in the parasellar region via supraorbital keyhole, frontotemporal
      pterional, and supraorbital approaches.
AB  - OBJECT: This study was designed to determine if the "keyhole concept," proposed
      by Perneczky's group, can be verified quantitatively. METHODS: Fourteen (3
      bilateral and 8 unilateral) sides of embalmed latex-injected cadaveric heads were
      dissected via 3 sequential craniotomy approaches: supraorbital keyhole,
      frontotemporal pterional, and supraorbital. Three-dimensional cartesian
      coordinates were recorded using a stereotactic localizer. The orthocenter of the
      ipsilateral anterior clinoid process, the posterior clinoid process, and the
      contralateral anterior clinoid process are expressed as a center point (the
      apex). Seven vectors project from the apex to their corresponding target points
      in a radiating manner on the parasellar skull base. Each 2 neighboring vectors
      border what could be considered a triangle, and the total area of the 7 triangles
      sharing the same apex was geometrically expressed as the area of exposure in the
      parasellar region. RESULTS: Values are expressed as the mean +/- SD (mm(2)). The
      total area of exposure was as follows: supraorbital keyhole 1733.1 +/- 336.0,
      pterional 1699.3 +/- 361.9, and supraorbital 1691.4 +/- 342.4. The area of
      exposure on the contralateral side was as follows: supraorbital keyhole 602.2 +/-
      194.7, pterional 595.2 +/- 228.0, and supraorbital 553.3 +/- 227.2. The
      supraorbital keyhole skull flap was 2.0 cm(2), and the skull flap size ratio was
      1:5:6.5 (supraorbital keyhole/pterional/supraorbital). CONCLUSIONS: The area of
      exposure of the parasellar region through the smaller supraorbital keyhole
      approach is as adequate as the larger pterional and supraorbital approaches. The
      keyhole concept can be verified quantitatively as follows: 1) a wide area of
      exposure on the skull base can be obtained through a small keyhole skull opening,
      and 2) the side opposite the opening can also be visualized.

PMID- 23140146
TI  - Hemorrhagic colloid cyst with intraventricular extension.
AB  - Colloid cysts of the third ventricle presenting with acute obstructive
      hydrocephalus due to intracystic and intraventricular hemorrhage are extremely
      rare. The authors report a case of a 43-year-old man with a hemorrhagic colloid
      cyst that was treated using endoscopic surgery. A small colloid cyst of the third
      ventricle was initially diagnosed in the patient, and he was treated
      conservatively at that time. On admission to the authors' institution he
      presented with sudden headache onset without neurological deficits. Computed
      tomography and MRI demonstrated a round hemorrhagic mass lesion in the third
      ventricle with bilateral intraventricular hemorrhage. Endoscopic resection was
      performed using a flexible videoscope. Only partial removal of the cyst was
      performed because of a tough cyst wall with highly viscous, hemorrhagic cystic
      contents. Histological examination revealed a typical colloid cyst wall and
      hemorrhage mixed within a mucinous substance. Postoperative serial neuroimaging
      demonstrated a gradual reduction in the residual cyst size and normalization in
      the lateral ventricle size.

PMID- 23140144
TI  - Targeted drug delivery for cancer therapy: the other side of antibodies.
AB  - Therapeutic monoclonal antibody (TMA) based therapies for cancer have advanced
      significantly over the past two decades both in their molecular sophistication
      and clinical efficacy. Initial development efforts focused mainly on humanizing
      the antibody protein to overcome problems of immunogenicity and on expanding of
      the target antigen repertoire. In parallel to naked TMAs, antibody-drug
      conjugates (ADCs) have been developed for targeted delivery of potent anti-cancer
      drugs with the aim of bypassing the morbidity common to conventional
      chemotherapy. This paper first presents a review of TMAs and ADCs approved for
      clinical use by the FDA and those in development, focusing on hematological
      malignancies. Despite advances in these areas, both TMAs and ADCs still carry
      limitations and we highlight the more important ones including cancer cell
      specificity, conjugation chemistry, tumor penetration, product heterogeneity and
      manufacturing issues. In view of the recognized importance of targeted drug
      delivery strategies for cancer therapy, we discuss the advantages of alternative
      drug carriers and where these should be applied, focusing on peptide-drug
      conjugates (PDCs), particularly those discovered through combinatorial peptide
      libraries. By defining the advantages and disadvantages of naked TMAs, ADCs and
      PDCs it should be possible to develop a more rational approach to the application
      of targeted drug delivery strategies in different situations and ultimately, to a
      broader basket of more effective therapies for cancer patients.

PMID- 23140147
TI  - PlGF and sVEGFR-1 in chronic subdural hematoma: implications for hematoma
      development.
AB  - OBJECT: A considerable body of evidence indicates that inflammation and
      angiogenesis play a significant role in the development and progression of
      chronic subdural hematoma (CSDH). While various experimental and clinical studies
      have implicated placental growth factor (PlGF) in the processes that underpin
      pathological angiogenesis, no study has thus far investigated its expression in
      CSDH. The actions of PlGF and its related proangiogenic vascular endothelial
      growth factor (VEGF) are antagonized by a high-affinity soluble receptor, namely
      soluble VEGF receptor-1 (sVEGFR-1), and thus the ratio between sVEGFR-1 and
      angiogenic factors provides an index of angiogenic capacity. METHODS: In the
      present study, using an automated electrochemiluminescence assay, levels of PlGF
      and sVEGFR-1 were quantified in serum and hematoma fluid obtained in 16 patients
      with CSDH. RESULTS: Levels of PlGF and sVEGFR-1 were significantly higher in
      hematoma fluid than in serum (p < 0.0001). In serum, levels of sVEGFR-1 were
      higher than those of PlGF (p < 0.0001), whereas in hematoma fluid this difference
      was not apparent. Furthermore, the ratio of sVEGFR-1 to PlGF was significantly
      lower in hematoma fluid than in serum (p < 0.0001). CONCLUSIONS: Given previous
      evidence indicating a role for PlGF in promoting angiogenesis, inflammatory cell
      chemotaxis, and stimulation, as well as its ability to amplify VEGF-driven
      signaling under conditions favoring pathological angiogenesis, enhanced
      expression of PlGF in hematoma fluid suggests the involvement of this factor in
      the mechanisms of inflammation and angiogenesis in CSDH. Furthermore, a reduced
      ratio of sVEGFR-1 to PlGF in hematoma fluid is consistent with the proangiogenic
      capacity of CSDH. Future studies are warranted to clarify the precise role of
      PlGF and sVEGFR-1 in CSDH.

PMID- 23140148
TI  - Vestibular schwannomas.

PMID- 23140149
TI  - Prevalence and natural history of arachnoid cysts in adults.
AB  - OBJECT: Arachnoid cysts are a frequent finding on intracranial imaging. The
      prevalence and natural history of these cysts in adults are not well defined.
      METHODS: We retrospectively reviewed the electronic medical records of a
      consecutive series of adults who underwent brain MRI over a 12-year interval to
      identify those with arachnoid cysts. The MRI studies were reviewed to confirm the
      diagnosis. For those patients with arachnoid cysts, we evaluated presenting
      symptoms, cyst size, and cyst location. Patients with more than 6 months'
      clinical and imaging follow-up were included in a natural history analysis.
      RESULTS: A total of 48,417 patients underwent brain MRI over the study period.
      Arachnoid cysts were identified in 661 patients (1.4%). Men had a higher
      prevalence than women (p < 0.0001). Multiple arachnoid cysts occurred in 30
      patients. The most common locations were middle fossa (34%), retrocerebellar
      (33%), and convexity (14%). Middle fossa cysts were predominantly left-sided
      (70%, p < 0.001). Thirty-five patients were considered symptomatic and 24
      underwent surgical treatment. Sellar and suprasellar cysts were more likely to be
      considered symptomatic (p < 0.0001). Middle fossa cysts were less likely to be
      considered symptomatic (p = 0.01. The criteria for natural history analysis were
      met in 203 patients with a total of 213 cysts. After a mean follow-up of 3.8 +/-
      2.8 years (for this subgroup), 5 cysts (2.3%) increased in size and 2 cysts
      decreased in size (0.9%). Only 2 patients developed new or worsening symptoms
      over the follow-up period. CONCLUSIONS: Arachnoid cysts are a common incidental
      finding on intracranial imaging in all age groups. Although arachnoid cysts are
      symptomatic in a small number of patients, they are associated with a benign
      natural history for those presenting without symptoms.

PMID- 23140150
TI  - Involvement of the right inferior longitudinal fascicle in visual hemiagnosia: a
      brain stimulation mapping study.
AB  - Neural foundations underlying visual agnosia are poorly understood. The authors
      present the case of a patient who underwent awake surgery for a right basal
      temporooccipital low-grade glioma in which direct electrostimulation was used
      both at the cortical and subcortical level. Brain mapping over the inferior
      longitudinal fascicle generated contralateral visual hemiagnosia. These original
      findings are in agreement with recent tractography data that have confirmed the
      existence of an occipitotemporal pathway connecting occipital visual input to
      higher-level processing in temporal lobe structures. This is the first report of
      a true transient visual hemiagnosia elicited through electrostimulation,
      supporting the crucial role of inferior longitudinal fascicle in visual
      recognition.

PMID- 23140151
TI  - Technical nuances of temporal muscle dissection and reconstruction for the
      pterional keyhole craniotomy.
AB  - The supraorbital keyhole approach offers a limited access for aneurysms located
      at the middle cerebral artery (MCA) bifurcation with long M(1) segments or
      proximal M(2) aneurysms. Alternative minimally invasive routes centered on the
      pterion have been developed to address these aneurysms. Appropriate dissection
      and reconstruction of the temporal muscle are important for optimal exposure and
      best cosmetic results with the pterional keyhole craniotomy. The authors describe
      the technical nuances of temporal muscle dissection and reconstruction adapted to
      the pterional keyhole craniotomy.   After incising the scalp in a curvilinear
      fashion behind the hairline, an interfascial dissection is performed, allowing
      anterior reflection of the superficial temporal fat pat and superficial temporal
      fascia. The temporal muscle is incised 7-10 mm below its insertion at the
      superior temporal line. The deep temporal fascia and temporal muscle are incised
      vertically, completing a T-shaped incision. Subperiosteal dissection of both
      muscle flaps preserves the deep temporal arteries and nerves. A craniotomy
      measuring 2.5-3 cm in diameter, based anteriorly at the pterion, is made over the
      sylvian fissure. Dissection of the sylvian fissure and of MCA aneurysms can
      proceed without the use of retractors. The bone flap and associated hardware is
      entirely covered by the temporal muscle, which is reconstructed in 2 layers: the
      temporal muscle/deep temporal fascia and the superficial temporal fascia.   This
      dissection technique prevents damage to branches of the facial nerve and
      minimizes temporal muscle damage. Dividing the temporal muscle vertically and
      reflecting both parts anteriorly and posteriorly prevents suboptimal illumination
      and visualization under the microscope. Covering the bone flap and related
      hardware with a multilayer anatomical reconstruction optimizes cosmetic results.

PMID- 23140152
TI  - Long-term safety and efficacy of stereotactic radiosurgery for vestibular
      schwannomas: evaluation of 440 patients more than 10 years after treatment with
      Gamma Knife surgery.
AB  - Object Little is known about long-term outcomes, including tumor control and
      adverse radiation effects, in patients harboring vestibular schwannomas (VSs)
      treated with stereotactic radiosurgery > 10 years previously. The aim of this
      study was to confirm whether Gamma Knife surgery (GKS) for VSs continues to be
      safe and effective > 10 years after treatment. Methods A total of 440 patients
      with VS (including neurofibromatosis Type 2) treated with GKS between May 1991
      and December 2000 were evaluable. Of these, 347 patients (79%) underwent GKS as
      an initial treatment and 93 (21%) had undergone prior resection. Three hundred
      fifty-eight patients (81%) had a solid tumor and 82 (19%) had a cystic tumor. The
      median tumor volume was 2.8 cm(3) and the median marginal dose was 12.8 Gy.
      Results The median follow-up period was 12.5 years. The actuarial 5- and >= 10
      year progression-free survival was 93% and 92%, respectively. No patient
      developed treatment failure > 10 years after treatment. According to multivariate
      analysis, significant factors related to worse progression-free survival included
      brainstem compression with a deviation of the fourth ventricle (p < 0.0001),
      marginal dose <= 13 Gy (p = 0.01), prior treatment (p = 0.02), and female sex (p
      = 0.02). Of 287 patients treated at a recent optimum dose of <= 13 Gy, 3 (1%)
      developed facial palsy, including 2 with transient palsy and 1 with persistent
      palsy after a second GKS, and 3 (1%) developed facial numbness, including 2 with
      transient and 1 with persistent facial numbness. The actuarial 10-year facial
      nerve preservation rate was 97% in the high marginal dose group (> 13 Gy) and
      100% in the low marginal dose group (<= 13 Gy). Ten patients (2.3%) developed
      delayed cyst formation. One patient alone developed malignant transformation,
      indicating an incidence of 0.3%. Conclusions In this study GKS was a safe and
      effective treatment for the majority of patients followed > 10 years after
      treatment. Special attention should be paid to cyst formation and malignant
      transformation as late adverse radiation effects, although they appeared to be
      rare. However, it is necessary to collect further long-term follow-up data before
      making conclusions about the long-term safety and efficacy of GKS, especially for
      young patients with VSs.

PMID- 23140153
TI  - Use of supramaximal stimulation to predict facial nerve outcomes following
      vestibular schwannoma microsurgery: results from a decade of experience.
AB  - OBJECT: The goal of vestibular schwannoma surgery is tumor removal and
      preservation of neural function. Intraoperative facial nerve (FN) monitoring has
      emerged as the standard of care, but its role in predicting long-term facial
      function remains a matter of debate. The present report seeks to describe and
      critically assess the value of applying current at supramaximal levels in an
      effort to identify patients destined for permanent facial paralysis. METHODS:
      Over more than a decade, the protocol for stimulating and assessing the FN during
      vestibular schwannoma surgery at the authors' institution has consisted of
      applying pulsed constant-current stimulation at supramaximal levels proximally
      and distally following tumor resection to generate an amplitude ratio, which
      subtracted from 100% yields the degree to which the functional integrity of the
      FN "dropped off" intraoperatively. These data were prospectively collected and
      additional variables that might impact postoperative FN function were
      retrospectively reviewed from the medical record. Only patients with anatomically
      intact FNs and > 12 months of follow-up data were analyzed. RESULTS: There were
      267 patients available for review. The average posterior fossa tumor diameter was
      24 mm and the rate of long-term good (House-Brackmann Grade I-II) FN function was
      84%. Univariate logistic regression analysis revealed that prior treatment,
      neurofibromatosis Type 2 status, tumor size, cerebellopontine angle extension,
      subjectively thinned FN at the time of operation, minimal stimulation threshold,
      percent dropoff by supramaximal stimulation (SMS), and postoperative FN function
      all correlated statistically (p < 0.05) with long-term FN function. When
      evaluating patients with significant FN weakness at the time of hospital
      discharge, only the percent dropoff by SMS remained a significant predictor of
      long-term FN function. However, the positive predictive value of SMS for long
      term weakness is low, at 46%. CONCLUSIONS: In a large cohort of patients, the
      authors found that interrogating intraoperative FN function with SMS is safe and
      technically simple. It is useful for predicting which patients will ultimately
      have good facial function, but is very limited in identifying patients destined
      for long-term facial weakness. This test may prove helpful in the future in
      tailoring less than gross-total tumor removal to limit postoperative facial
      weakness.

PMID- 23140155
TI  - Radiation-induced imaging changes following Gamma Knife surgery for cerebral
      arteriovenous malformations.
AB  - OBJECT: The objective of this study was to evaluate the incidence, severity,
      clinical manifestations, and risk factors of radiation-induced imaging changes
      (RIICs) following Gamma Knife surgery (GKS) for cerebral arteriovenous
      malformations (AVMs). METHODS: A total of 1426 GKS procedures performed for AVMs
      with imaging follow-up available were analyzed. Radiation-induced imaging changes
      were defined as newly developed increased T2 signal surrounding the treated AVM
      nidi. A grading system was developed to categorize the severity of RIICs. Grade I
      RIICs were mild imaging changes imposing no mass effect on the surrounding brain.
      Grade II RIICs were moderate changes causing effacement of the sulci or
      compression of the ventricles. Grade III RIICs were severe changes causing
      midline shift of the brain. Univariate and multivariate logistic regression
      analyses were applied to test factors potentially affecting the occurrence,
      severity, and associated symptoms of RIICs. RESULTS: A total of 482 nidi (33.8%)
      developed RIICs following GKS, with 281 classified as Grade I, 164 as Grade II,
      and 37 as Grade III. The median duration from GKS to the development of RIICs was
      13 months (range 2-124 months). The imaging changes disappeared completely within
      2-128 months (median 22 months) following the development of RIICs. The RIICs
      were symptomatic in 122 patients, yielding an overall incidence of symptomatic
      RIICs of 8.6%. Twenty-six patients (1.8%) with RIICs had permanent deficits. A
      negative history of prior surgery, no prior hemorrhage, large nidus, and a single
      draining vein were associated with a higher risk of RIICs. CONCLUSIONS: Radiation
      induced imaging changes are the most common adverse effects following GKS.
      Fortunately, few of the RIICs are symptomatic and most of the symptoms are
      reversible. Patients with a relatively healthy brain and nidi that are large, or
      with a single draining vein, are more likely to develop RIICs.

PMID- 23140156
TI  - Timing of cranioplasty after decompressive craniectomy for ischemic or
      hemorrhagic stroke.
AB  - OBJECT: The optimal timing of cranioplasty after decompressive craniectomy for
      stroke is not known. Case series suggest that early cranioplasty is associated
      with higher rates of infection while delaying cranioplasty may be associated with
      higher rates of bone resorption. The authors examined whether the timing of
      cranioplasty after decompressive craniectomy for stroke affects postoperative
      complication rates. METHODS: A retrospective cohort study was undertaken to
      evaluate complication rates in patients undergoing cranioplasty at early (within
      10 weeks of craniectomy) or late (>= 10 weeks) stages. Multivariate logistic
      regression analysis was used to determine characteristics that would predict
      complications in patients undergoing cranioplasty after decompressive craniectomy
      for stroke. RESULTS: While the overall complication rate was higher in the early
      cranioplasty cohort (22% vs 16% in the late cranioplasty cohort), the difference
      was not statistically significant (p = 0.5541). Patients in the early
      cranioplasty cohort had lower rates of postoperative hematoma but higher rates of
      infection. Presence of a CSF shunt was the only significant predictor of
      complications (OR 8.96, 95% CI 1.84-43.6). CONCLUSIONS: Complications rates for
      early cranioplasty (within 10 weeks of craniectomy) are similar to those
      encountered when cranioplasty is delayed, although the cohort size in this study
      was too small to state equivalence. Patients with a ventriculoperitoneal shunt
      are at higher risk for complications after cranioplasty.

PMID- 23140154
TI  - Neuroprotective effect of preoperatively induced mild hypothermia as determined
      by biomarkers and histopathological estimation in a rat subdural hematoma
      decompression model.
AB  - OBJECT: In patients who have sustained a traumatic brain injury (TBI),
      hypothermia therapy has not shown efficacy in multicenter clinical trials. Armed
      with the post hoc data from the latest clinical trial (National Acute Brain
      Injury Study: Hypothermia II), the authors hypothesized that hypothermia may be
      beneficial in an acute subdural hematoma (SDH) rat model by blunting the effects
      of ischemia/reperfusion injury. The major aim of this study was to test the
      efficacy of temperature management in reducing brain damage after acute SDH.
      METHODS: The rats were induced with acute SDH and placed into 1 of 4 groups: 1)
      normothermia group (37 degrees C); 2) early hypothermia group, head and body
      temperature reduced to 33 degrees C 30 minutes prior to craniotomy; 3) late
      hypothermia group, temperature lowered to 33 degrees C 30 minutes after
      decompression; and 4) sham group, no acute SDH (only craniotomy with
      normothermia). To assess for neuronal and glial cell damage, the authors analyzed
      microdialysate concentrations of GFAP and ubiquitin carboxyl-terminal hydrolase
      L1 (UCH-L1) by using a 100-kD probe. Fluoro-Jade B-positive neurons and injury
      volume with 2,3,5-triphenyltetrazolium chloride staining were also measured.
      RESULTS: In the early phase of reperfusion (30 minutes, 2.5 hours after
      decompression), extracellular UCH-L1 in the early hypothermia group was
      significantly lower than in the normothermia group (early, 4.9 +/- 1.0 ng/dl;
      late, 35.2 +/- 12.1 ng/dl; normothermia, 50.20 +/- 28.3 ng/dl; sham, 3.1 +/- 1.3
      ng/dl; early vs normothermia, p < 0.01; sham vs normothermia, p < 0.01, analyzed
      using ANOVA followed by a post hoc Bonferroni test). In the late phase of
      reperfusion (> 2.5 hours after decompression), extracellular GFAP in the early
      hypothermia group was also lower than in the normothermia and late hypothermia
      groups (early, 5.5 +/- 2.9 ng/dl; late, 7.4 +/- 3.4 ng/dl; normothermia, 15.3 +/-
      8.4 ng/dl; sham, 3.3 +/- 1.0 ng/dl; normothermia vs sham; p < 0.01). The number
      of Fluoro-Jade B-positive cells in the early hypothermia group was significantly
      smaller than that in the normothermia group (normothermia vs early: 774,588 +/-
      162,173 vs 180,903 +/- 42,212, p < 0.05). Also, the injury area and volume were
      smaller in the early hypothermia group in which hypothermia was induced before
      craniotomy and cerebral reperfusion (early, 115.2 +/- 15.4 mm(3); late, 344.7 +/-
      29.1 mm(3); normothermia, 311.2 +/- 79.2 mm(3); p < 0.05). CONCLUSIONS: The data
      suggest that early, preoperatively induced hypothermia could mediate the
      reduction of neuronal and glial damage in the reperfusion phase of
      ischemia/reperfusion brain injury.

PMID- 23140157
TI  - Combined proximal nerve graft and distal nerve transfer for a posterior cord
      brachial plexus injury.
AB  - The treatment of patients with prolonged denervation from a posterior cord
      brachial plexus injury is challenging and no management guidelines exist to
      follow. The authors describe the case of a 26-year-old man who presented to our
      clinic for treatment 11 months after suffering a high-energy injury to the
      posterior cord of the brachial plexus. A combined 9-cm proximal cable nerve graft
      procedure and a pronator branch to the posterior interosseous nerve transfer were
      performed. Satisfactory deltoid, triceps, wrist, and finger extensor recovery was
      noted 3 years after surgery. Patients with prolonged denervation from posterior
      cord injuries can be successfully treated with a combination of a proximal nerve
      graft and a distal nerve transfer.

PMID- 23140158
TI  - Traditional male circumcision for reducing the risk of HIV infection:
      perspectives of young people in South Africa.
AB  - Increasing evidence suggests that medical male circumcision is associated with a
      reduced risk of HIV infection for men in sub-Saharan Africa. The aim of this
      study was to understand the importance of male circumcision as a risk-reducing
      strategy by exploring perceptions of young men and women. The study draws on
      focus-group discussions conducted with both men and women in South Africa. The
      findings suggest that there is widespread support for traditional male
      circumcision. Traditional circumcision is viewed as a key part of the initiation
      process. However, a number of concerns were raised about the traditional
      initiation process, which may lead to risky sexual behaviours, including early
      sexual debut and multiple sexual partners. In addition, the risky sexual
      behaviour of men puts women at risk of HIV infection.

PMID- 23140159
TI  - Novel insights into Mycobacterium antigen Ag85 biology and implications in
      countermeasures for M. tuberculosis.
AB  - Tuberculosis remains one of the most prevalent and deadly infectious diseases,
      largely due to the emergence of multidrug-resistant and extensive drug-resistant
      Mycobacterium tuberculosis, especially the coinfection with HIV. Mycobacterium
      Ag85 complex (Ag85A, B, and C), with a carboxylesterase consensus sequence and
      conserved surface catalysis residues, involves in cell wall biosynthesis and the
      trigger of the host immune response. The physiological function, structures,
      distributions, and molecular mechanisms of regulations as well as their
      implications in novel vaccines and diagnostics against tuberculosis are
      summarized. Special focus is the regulation underlying the Ag85 expression. This
      will facilitate in-depth understanding of the role of Ag85 and developing better
      novel measures against M. tuberculosis infection.

PMID- 23140160
TI  - MicroRNAs in human lymphoblastoid cell lines.
AB  - Human lymphoblastoid cell lines (LCLs) are generated by EBV-mediated B-cell
      transformation to provide unlimited genomic resources for human genetics and
      immunological studies. The LCL is a good in vitro cell model for assessing
      population differences in the basal expression of genes and miRNAs as well as in
      cellular responses to various stimulators. Recently, the utility of LCLs was
      extended to pharmacogenomic studies to discover genetic factors underlying
      individual variations in response to chemicals and environmental stresses.
      Although LCLs represent generally lymphoid tissue-specific biological
      characteristics, genomic signatures of LCLs can distinguish patients with brain
      related diseases and nonlymphoid tumors from normal controls. MicroRNA is known
      to be an epigenetic transcriptional regulator, and its expression is induced in
      abnormal conditions such as perturbagen-stimulated, virus-infected, or cancer
      cells. The epigenetic regulation of gene expression mediated by microRNA and DNA
      methylation is important for understanding the pathogenesis of cancers and
      complex diseases as well as discovering for therapeutic targets. For integrative
      genomic analyses, LCLs can be utilized to generate cellular phenotypes and
      various genomic data (e.g., SNP, CNV, transcriptome, methylome, etc.), which can
      be linked to clinical information of donors. Here, we discuss miRNA-mediated gene
      expression in LCLs and its application to disease genomics and global
      transcriptional regulatory machinery studies.

PMID- 23140161
TI  - Recombinant laccase: II. Medical biosensor.
AB  - Langmuir-Blodgett (LB) technology was used to build a high-sensitivity enzyme
      based biosensor for medical purposes. Recombinant fungal laccase from
      Rigidoporous lignosus, as previously described, was used to catalyze a widely
      used antidepressant in a micromolar range, namely, clomipramine. The topological
      properties of the laccase thin film were characterized via LB pi-A isotherm and
      AFM (mean roughness 8.22 nm, compressibility coefficient 37.5 m/N). The
      sensitivity of the biosensor was investigated via UV spectroscopy, and linearity
      was found in the absorbance peak shift at 400 nm at drug concentration varying up
      to 20 uM. The enzyme kinetics was subsequently investigated with potentiometric
      and amperometric measurements, and we found electronic transfer of at least 1
      electron, k(s) 0.57 s(-1), diffusion coefficient 3 * 10(-6) cm(2)/s, K(cat)
      6825.92 min(-1), K(M) 4.1 uM, K(cat)/K(M) 2.8 * 10(7) mol(-1) s(-1), sensitivity
      of 440 nA/uM, maximum velocity 1706.48 nA/s, and response time less than 5 s. The
      amperometric and potentiometric measurements were repeated after a month,
      confirming the stability of the biosensor.

PMID- 23140163
TI  - Langmuir-Blodgett nanotemplate and radiation resistance in protein crystals:
      state of the art.
AB  - A state-of-the-art review of the role of the Langmuir-Blodgett nanotemplate on
      protein crystal structures is here presented. Crystals grown by nanostructured
      template appear more radiation resistant than the classical ones, even in the
      presence of a third-generation highly focused beam at the European Synchrotron
      Radiation Facility. The electron density maps and the changes in parameters such
      as total diffractive power, B-factor, and pairwise R-factor have been discussed.
      Protein crystals, grown by the Langmuir-Blodgett nanotemplate-based method,
      proved to be more radiation resistant compared to crystals grown by the classical
      hanging drop method in terms of both global and specific damage.

PMID- 23140162
TI  - Nmp4/CIZ closes the parathyroid hormone anabolic window.
AB  - Chronic degenerative diseases are increasing with the aging U.S. population. One
      consequence of this phenomenon is the need for long-term osteoporosis therapies.
      Parathyroid hormone (PTH), the only FDA-approved treatment that adds bone to the
      aged skeleton, loses its potency within two years of initial treatment but the
      mechanism regulating its limited "anabolic window" is unknown. We have discovered
      that disabling the nucleocytoplasmic shuttling transcription factor nuclear
      matrix protein 4/cas interacting zinc finger protein (Nmp4/CIZ) in mice extends
      the PTH bone-forming capacity. Nmp4 was discovered during our search for nuclear
      matrix transcription factors that couple this hormone's impact on osteoblast
      cytoskeletal and nuclear organization with its anabolic capacity. CIZ was
      independently discovered as a protein that associates with the focal adhesion
      associated mechanosensor p130Cas. The Nmp4/CIZ-knockout (KO) skeletal phenotype
      exhibits a modestly enhanced bone mineral density but manifests an exaggerated
      response to both PTH and to BMP2 and is resistant to disuse-induced bone loss.
      The cellular basis of the global Nmp4/CIZ-KO skeletal phenotype remains to be
      elucidated but may involve an expansion of the bone marrow osteoprogenitor
      population along with modestly enhanced osteoblast and osteoclast activities
      supporting anabolic bone turnover. As a shuttling Cys(2)His(2) zinc finger
      protein, Nmp4/CIZ acts as a repressive transcription factor perhaps associated
      with epigenetic remodeling complexes, but the functional significance of its
      interaction with p130Cas is not known. Despite numerous remaining questions,
      Nmp4/CIZ provides insights into how the anabolic window is regulated, and itself
      may provide an adjuvant therapy target for the treatment of osteoporosis by
      extending PTH anabolic efficacy.

PMID- 23140164
TI  - Tuberculosis and sexual inequality: the role of sex hormones in immunity.
AB  - The role of sex hormones is profound and diverse. The gender and age differences
      in TB incidences suggest a role of hormones. These data, together with their
      relevance to the epidemiology of tuberculosis, are gathered and analyzed in this
      review. The underlying network of hormones functionalities in TB is also
      proposed.

PMID- 23140165
TI  - Edible vaccine: a new platform for the development of malaria vaccine.
AB  - The plasmodium vivax is the most prevalent malaria parasite. The world
      essentially needs a malaria vaccine to alleviate the human suffering associated
      with the parasitic disease that kills more than one million people annually. The
      use of plants for the expression of the proteins of disease-causing vehicle in
      transgenic plants has been increasingly used in the development of experimental
      vaccines, largely oriented to the improvement of edible vaccines. Currently,
      through modern biotechnology, there has been a revival in obtaining a new edible
      vaccine against the malaria parasite from plant sources. Through genetic
      alteration, it is now recognized that plants are potentially a new source of
      recombinant proteins including vaccines, antibodies, blood substitutes, and other
      therapeutic entities. Plant-derived antibodies and other proteins are mostly
      valuable since they are free of mammalian viral vectors and human pathogens.
      Although significant progress has been achieved in the research for edible
      vaccine in Plasmodium falciparum, limited progress has been made in the
      Plasmodium vivax component that might be eligible for edible vaccine development.
      We describe the overall strategy recommended by plants, which include high
      biomass production and low cost of cultivation, relatively fast "gene to protein"
      time, low capital and operating costs, outstanding scalability, eukaryotic
      posttranslational modifications, and a relatively high protein yield.

PMID- 23140167
TI  - Roles of peptidoglycan recognition protein (PGRP) in immunity and implications
      for novel anti-infective measures.
AB  - Peptidoglycan recognition protein (PGRP) is an important host innate immunity arm
      capable of peptidoglycan and allied bacteria recognition. PGRP belongs to host
      pattern recognition receptors (PRRs) responsible for pathogen associated
      molecular patterns recognition, such as lipopolysaccharide, lipoteichoic acid,
      PGN, and mannose. As an essential host PRR, PGRP is well conserved from insects
      to mammals. The distribution, structure, function, regulation of gene expression,
      and evolution of PGRP from insects and mammals were summarized to furnish
      insights into this important molecule family.

PMID- 23140166
TI  - Tumor suppressor maspin as a rheostat in HDAC regulation to achieve the fine
      tuning of epithelial homeostasis.
AB  - Maspin, a class II tumor suppressor, is often downregulated during tumor
      progression and its depletion from the nucleus is associated with poor prognosis.
      Recently, we reported that reintroduction of maspin is sufficient for
      redifferentiation of prostate cancer cells to epithelial phenotype, a reversal of
      epithelial-to-mesenchymal transition. We have linked this effect of maspin with
      its ability to directly inhibit HDAC1, thereby influencing the acetylation state
      of transcription factors and other proteins. Maspin overexpression leads to
      changes in the expression level of a large number of proteins and these changes
      are often microenvironment specific. In this review, we summarize the epigenetic
      effects of maspin and provide comprehensive bioinformatic analysis of microarray
      derived gene expression changes caused by maspin in different microenvironments.
      The analysis was performed on multiple levels, including identification of
      statistically enriched gene ontology groups, detection of overreprepresented
      transcription factors binding sites in promoters of differentially expressed
      genes, followed by searching for key nodes of regulatory networks controlling
      these transcription factors. The results are consistent with our hypothesis that
      maspin serves as an endogenous regulator of HDAC activity and suggest that the
      effect of maspin is primarily mediated by TGFbeta, beta-catenin/E-cadherin
      pathways, and network key nodes such as Abl kinase, p62, IL1, and caspases 6 and
      8.

PMID- 23140168
TI  - The rise of the Himalaya enforced the diversification of SE Asian ferns by
      altering the monsoon regimes.
AB  - BACKGROUND: The rise of high mountain chains is widely seen as one of the factors
      driving rapid diversification of land plants and the formation of biodiversity
      hotspots. Supporting evidence was reported for the impact of the rapid rise of
      the Andean mountains but this hypothesis has so far been less explored for the
      impact of the "roof of the world". The formation of the Himalaya, and especially
      the rise of the Qinghai-Tibetan Plateau in the recent 20 million years, altered
      the monsoon regimes that dominate the current climates of South East Asia. Here,
      we infer the hypothesis that the rise of Himalaya had a strong impact on the
      plant diversity in the biodiversity hotspot of the Southwest Chinese Mountains.
      RESULTS: Our analyses of the diversification pattern of the derived fern genus
      Lepisorus recovered evidence for changes in plant diversity that correlated with
      the strengthening of South East Asian monsoon. Southwest China or Southwest China
      and Japan was recovered as the putative area of origin of Lepisorus and enhancing
      monsoon regime were found to shape the early diversification of the genus as well
      as subsequent radiations during the late Miocene and Pliocene. CONCLUSIONS: We
      report new evidence for a coincidence of plant diversification and changes of the
      climate caused by the uplift of the Himalaya. These results are discussed in the
      context of the impact of incomplete taxon sampling, uncertainty of divergence
      time estimates, and limitations of current methods used to assess diversification
      rates.

PMID- 23140169
TI  - Potential benefits of cyproheptadine in HIV-positive patients under treatment
      with antiretroviral drugs including efavirenz.
AB  - INTRODUCTION: More than 50% of HIV-positive patients experience neuropsychiatric
      adverse reactions following efavirenz therapy. Discontinuation of efavirenz due
      to its neuropsychiatric side effects has been reported in 2 - 13% of patients.
      Dizziness, headache, nightmares, abnormal dreams, mild cognitive difficulty,
      sleep disturbance (somnolence and insomnia), impaired concentration, depression,
      hallucination, delusion, paranoia, anxiety, agitation, aggressive behavior,
      mania, emotional labiality, catatonia, melancholia, psychosis, and fatigue are
      the most reported efavirenz adverse reactions. AREAS COVERED: In this review,
      potential benefits of cyproheptadine in prevention and management of
      HIV/antiretroviral-associated neuropsychiatric complications are evaluated. The
      available evidence was collected by searching Scopus, PubMed, Medline, Cochrane
      central register of controlled trials, and Cochrane database systematic reviews.
      EXPERT OPINION: Cyproheptadine is a cheap and safe drug that does not have
      significant interactions with antiretroviral drugs. Cyproheptadine's common side
      effects including increasing appetite and weight gain can be useful in HIV
      positive individuals with their decreased appetite and weight loss. There is
      limited evidence regarding the effectiveness of cyproheptadine in
      neuropsychiatric disorders. It is essential to evaluate cyproheptadine efficacy
      in the prevention and management of neuropsychiatric complications of
      HIV/antiretroviral infection in well-designed studies in the future.

PMID- 23140170
TI  - Chemometrics.

PMID- 23140172
TI  - P2Y12 protects platelets from apoptosis via PI3k-dependent Bak/Bax inactivation.
AB  - BACKGROUND: Platelet ADP receptor P2Y(12) is well studied and recognized as a key
      player in platelet activation, hemostasis and thrombosis. However, the role of
      P2Y(12) in platelet apoptosis remains unknown. OBJECTIVES: To evaluate the role
      of the P2Y(12) receptor in platelet apoptosis. METHODS: We used flow cytometry
      and Western blotting to assess apoptotic events in platelets treated with ABT-737
      or ABT-263, and stored at 37 degrees C, combined with P2Y(12) receptor
      antagonists or P2Y(12) -deficient mice. RESULTS:  P2Y(12) activation attenuated
      apoptosis induced by ABT-737 in human and mouse platelets in vitro, evidenced by
      reduced phosphatidylserine (PS) exposure, diminished depolarization of
      mitochondrial inner transmembrane potential (DeltaPsim) and decreased caspase-3
      activation. Through increasing the phosphorylation level of Akt and Bad, and
      changing the interaction between different Bcl-2 family proteins, P2Y(12)
      activation inactivated Bak/Bax. This antiapoptotic effect could be abolished by
      P2Y(12) antagonism or PI3K inhibition. We also observed the antiapoptotic effect
      of P2Y(12) activation in platelets stored at 37 degrees C. P2Y(12) activation
      improved the impaired activation responses of apoptotic platelets stressed by ABT
      737. In platelets from mice dosed with ABT-263 in vivo, clopidogrel or deficiency
      of P2Y(12) receptor enhanced apoptosis along with increased Bak/Bax activation.
      CONCLUSIONS: This study demonstrates that P2Y(12) activation protects platelets
      from apoptosis via PI3k-dependent Bak/Bax inactivation, which may be
      physiologically important to counter the proapoptotic challenge. Our findings
      that P2Y(12) blockade exaggerates platelet apoptosis induced by ABT-263
      (Navitoclax) also imply a novel drug interaction of ABT-263 and P2Y(12)
      antagonists.

PMID- 23140171
TI  - Targeting of conserved gag-epitopes in early HIV infection is associated with
      lower plasma viral load and slower CD4(+) T cell depletion.
AB  - We aimed to investigate whether the character of the immunodominant HIV-Gag
      peptide (variable or conserved) targeted by CD8(+) T cells in early HIV infection
      would influence the quality and quantity of T cell responses, and whether this
      would affect the rate of disease progression. Treatment-naive HIV-infected study
      subjects within the OPTIONS cohort at the University of California, San
      Francisco, were monitored from an estimated 44 days postinfection for up to 6
      years. CD8(+) T cells responses targeting HLA-matched HIV-Gag-epitopes were
      identified and characterized by multicolor flow cytometry. The autologous HIV gag
      sequences were obtained. We demonstrate that patients targeting a conserved HIV
      Gag-epitope in early infection maintained their epitope-specific CD8(+) T cell
      response throughout the study period. Patients targeting a variable epitope
      showed decreased immune responses over time, although there was no limitation of
      the functional profile, and they were likely to target additional variable
      epitopes. Maintained immune responses to conserved epitopes were associated with
      no or limited sequence evolution within the targeted epitope. Patients with
      immune responses targeting conserved epitopes had a significantly lower median
      viral load over time compared to patients with responses targeting a variable
      epitope (0.63 log(10) difference). Furthermore, the rate of CD4(+) T cell decline
      was slower for subjects targeting a conserved epitope (0.85% per month) compared
      to subjects targeting a variable epitope (1.85% per month). Previous studies have
      shown that targeting of antigens based on specific HLA types is associated with a
      better disease course. In this study we show that categorizing epitopes based on
      their variability is associated with clinical outcome.

PMID- 23140173
TI  - Functionalizing Ti-surfaces through the EPD of hydroxyapatite/nanoY2O3.
AB  - Ceramic materials for skeletal repair and reconstruction are expanding to a
      number of different applications. Present research is addressing new compositions
      and performances to promote osseo-integration through metal coatings.
      Nanotechnology plays a key role in this research because nanostructures can be
      introduced into implants to functionalize them and/or to enhance their
      properties, such as the thermal or mechanical response. In this work, the
      insertion of Y(2)O(3) nanoparticles into a hydroxyapatite (HA) coating of Ti
      using colloidal processing technology was developed. The suspensions of HA and
      Y(2)O(3) nanoparticles were formulated with a focus on zeta potential, particle
      size distribution, and viscosity for the codeposition of both phases by
      electrophoresis. The microstructure of the nanocomposite coating was optimized by
      adjusting the main parameters of the electrophoretic deposition process. A
      threshold value of the applied electric field for the composite shaping was
      identified. The results demonstrate that the Y(2)O(3) nanoparticles are
      homogeneously distributed in the coating and decrease in concentration as the
      distance from the substrate increases. As a consequence of the presence of the
      Y(2)O(3), delays in the HA thermal decomposition and the improvement of metal
      ceramic joining were observed.

PMID- 23140174
TI  - CDK2 regulates HIV-1 transcription by phosphorylation of CDK9 on serine 90.
AB  - BACKGROUND: HIV-1 transcription is activated by the viral Tat protein that
      recruits host positive transcription elongation factor-b (P-TEFb) containing
      CDK9/cyclin T1 to the HIV-1 promoter. P-TEFb in the cells exists as a lower
      molecular weight CDK9/cyclin T1 dimer and a high molecular weight complex of 7SK
      RNA, CDK9/cyclin T1, HEXIM1 dimer and several additional proteins. Our previous
      studies implicated CDK2 in HIV-1 transcription regulation. We also found that
      inhibition of CDK2 by iron chelators leads to the inhibition of CDK9 activity,
      suggesting a functional link between CDK2 and CDK9. Here, we investigate whether
      CDK2 phosphorylates CDK9 and regulates its activity. RESULTS: The siRNA-mediated
      knockdown of CDK2 inhibited CDK9 kinase activity and reduced CDK9
      phosphorylation. Stable shRNA-mediated CDK2 knockdown inhibited HIV-1
      transcription, but also increased the overall level of 7SK RNA. CDK9 contains a
      motif (90SPYNR94) that is consensus CDK2 phosphorylation site. CDK9 was
      phosphorylated on Ser90 by CDK2 in vitro. In cultured cells, CDK9 phosphorylation
      was reduced when Ser90 was mutated to an Ala. Phosphorylation of CDK9 on Ser90
      was also detected with phospho-specific antibodies and it was reduced after the
      knockdown of CDK2. CDK9 expression decreased in the large complex for the CDK9
      S90A mutant and was correlated with a reduced activity and an inhibition of HIV-1
      transcription. In contrast, the CDK9-S90D mutant showed a slight decrease in CDK9
      expression in both the large and small complexes but induced Tat-dependent HIV-1
      transcription. Molecular modeling showed that Ser 90 of CDK9 is located on a
      flexible loop exposed to solvent, suggesting its availability for
      phosphorylation. CONCLUSION: Our data indicate that CDK2 phosphorylates CDK9 on
      Ser 90 and thereby contributes to HIV-1 transcription. The phosphorylation of
      Ser90 by CDK2 represents a novel mechanism of HIV-1 regulated transcription and
      provides a new strategy for activation of latent HIV-1 provirus.

PMID- 23140175
TI  - The influence of hallucination proneness and social threat on time perception.
AB  - INTRODUCTION: Individuals with schizophrenia frequently report disturbances in
      time perception, but the precise nature of such deficits and their relation to
      specific symptoms of the disorder is unclear. We sought to determine the
      relationship between hallucination proneness and time perception in healthy
      individuals, and whether this relationship is moderated by hypervigilance to
      threat-related stimuli. METHODS: 206 participants completed the Revised Launay
      Slade Hallucination Scale (LSHS-R) and a time reproduction task in which, on each
      trial, participants viewed a face (happy, angry, neutral, or fearful) for between
      1 and 5 s and then reproduced the time period with a spacebar press. RESULTS:
      High LSHS-R scores were associated with longer time estimates, but only during
      exposure to angry faces. A factor analysis of LSHS-R scores identified a factor
      comprising items related to reality monitoring, and this factor was most
      associated with the longer time estimates. CONCLUSIONS: During exposure to
      potential threat in the environment, duration estimates increase with
      hallucination proneness. The experience of feeling exposed to threat for longer
      may serve to maintain a state of hypervigilance which has been shown previously
      to be associated with positive symptoms of schizophrenia.

PMID- 23140176
TI  - Milk thistle and its derivative compounds: a review of opportunities for
      treatment of liver disease.
AB  - Milk thistle extracts have been used as a "liver tonic" for centuries. In recent
      years, silibinin, the active ingredient in milk thistle extracts, has been
      studied both in vitro and in vivo to evaluate the beneficial effects in hepatic
      disease. Silibinin increases antioxidant concentrations and improves outcomes in
      hepatic diseases resulting from oxidant injury. Silibinin treatment has been
      associated with protection against hepatic toxins, and also has resulted in
      decreased hepatic inflammation and fibrosis. Limited information currently is
      available regarding silibinin use in veterinary medicine. Future study is
      justified to evaluate dose, kinetics, and treatment effects in domestic animals.

PMID- 23140178
TI  - A biomechanical model for a new incremental technique for tooth restoration.
AB  - The objective of this study is to introduce a modified incremental technique that
      leads to improved marginal adaptation and to develop a mathematical model that
      explains the results obtained. The technique proposed is a two-step incremental
      technique that reduces volume of a resin that is polymerized at each step and
      eliminates the central point in resin, so that the stresses are additionally
      reduced. In the first step, the resin is placed in the cylindrical cavity with a
      conical dental instrument embedded in the middle of restoration. After
      polymerization, the conical dental instrument is removed and the conical hole is
      filled with the second layer of composite and polymerized. This technique is a
      variant of a method where singular stress point is eliminated. We modified the
      previous technique by introducing a conical dental instrument into the centre of
      the cavity. The procedure proposed was compared with the bulk and horizontal
      layer incremental technique. This study confirmed that the incremental type
      placement technique used here has better marginal adaptation than bulk technique
      and horizontal two-layer incremental technique although it has larger C-factor in
      the first step than the two-layer incremental technique. Thus, the elimination of
      the central point of restoration leads to better marginal adaptation. Conical
      shape of the cavity that is filled in the second step makes this technique easy
      to apply in clinical conditions. A mathematical model describing stresses in the
      restoration shows stress reduction as a consequence of applying the procedure
      proposed.

PMID- 23140177
TI  - Novel antiviral activity of baicalein against dengue virus.
AB  - BACKGROUND: Dengue is a serious arboviral disease currently with no effective
      antiviral therapy or approved vaccine available. Therefore, finding the effective
      compound against dengue virus (DENV) replication is very important. Among the
      natural compounds, bioflavonoids derived mainly from plants are of interest
      because of their biological and medicinal benefits. METHODS: In the present
      study, antiviral activity of a bioflavonoid, baicalein, was evaluated against
      different stages of dengue virus type 2 (DENV-2) replication in Vero cells using
      focus forming unit reduction assay and quantitative RT-PCR. RESULTS: Baicalein
      inhibited DENV-2 replication in Vero cells with IC50= 6.46 MUg/mL and SI= 17.8
      when added after adsorption to the cells. The IC50 against DENV-2 was 5.39 MUg/mL
      and SI= 21.3 when cells were treated 5 hours before virus infection and
      continuously up to 4 days post infection. Baicalein exhibited direct virucidal
      effect against DENV-2 with IC 50= 1.55 MUg/mL and showed anti-adsorption effect
      with IC50 = 7.14 MUg/mL. CONCLUSIONS: Findings presented here suggest that
      baicalein exerts potent antiviral activity against DENV. Baicalein possesses
      direct virucidal activity against DENV besides its effects against dengue virus
      adsorption and intracellular replication of DENV-2. Baicalein, hence, should be
      considered for in vivo evaluation in the development of an effective antiviral
      compound against DENV.

PMID- 23140179
TI  - Compensatory nature of Chargaff's second parity rule.
AB  - The second parity rule of Chargaff (A~T and G~C within one strand) holds all over
      the living world with minor exceptions. It is maintained with higher accuracy for
      long sequences. The question addressed in the article is how different sequence
      types, with different biases from the parity, contribute to the general effect.
      It appears that the sequence segments with biases of opposite sign are
      intermingled, so that with sufficient sequence lengths the parity is established.
      The parity rule seems to be a cumulative result of a number of independent
      processes in the genome evolution, with the parity as their intrinsic property.
      Symmetrical appearance of simple repeats and of Alu sequences in the human DNA
      strands, and other contributions to the Chargaff parity II rule are discussed. 

PMID- 23140180
TI  - Rapid purification of ribosomal particles assembled on histone H4 mRNA: a new
      method based on mRNA-DNA chimaeras.
AB  - Detailed knowledge of the structure of the ribosomal particles during their
      assembly on mRNA is a prerequisite for understanding the intricate translation
      initiation process. In vitro preparation of eukaryotic translation initiation
      complexes is limited by the rather tricky assembly from individually purified
      ribosomal subunits, initiation factors and initiator tRNA. In order to directly
      isolate functional complexes from living cells, methods based on affinity tags
      have been developed which, however, often suffer from non-specific binding of
      proteins and/or RNAs. In the present study we present a novel method designed for
      the purification of high-quality ribosome/mRNA particles assembled in RRL (rabbit
      reticulocyte lysate). Chimaerical mRNA-DNA molecules, consisting of the full
      length mRNA ligated to a biotinylated desoxy-oligonucleotide, are immobilized on
      streptavidin-coated beads and incubated with RRL to form initiation complexes.
      After a washing step, the complexes are eluted by specific DNase I digestion of
      the DNA moiety of the chimaera, releasing initiation complexes in native
      conditions. Using this simple and robust purification setup, 80S particles
      properly programmed with full-length histone H4 mRNA were isolated with the
      expected ribosome/mRNA molar ratio of close to 1. We show that by using this
      novel approach purified ribosomal particles can be obtained that are suitable for
      biochemical and structural studies, in particular single-particle cryo-EM (cryo
      electron microscopy). This purification method thus is a versatile tool for the
      isolation of fully functional RNA-binding proteins and macromolecular RNPs.

PMID- 23140182
TI  - Challenging homophobia and heterosexism through storytelling and critical
      dialogue among Hong Kong Chinese immigrant parents in Toronto.
AB  - Homophobia and heterosexism are ubiquitous in Canadian society. They contribute
      to significant health and mental health disparities for lesbian, gay and bisexual
      youth and their families. Anti-homophobia efforts tend to focus on students and
      teachers at school. While these efforts are important, they do not reach parents,
      who play an important role in shaping young people's attitudes towards gender and
      sexuality. To eliminate bullying and victimisation associated with homophobia at
      school and in the community, concerted efforts are urgently needed to mobilise
      parents to become champions against homophobia and heterosexism. In this paper,
      we report on our use of storytelling and critical dialogue to engage a group of
      Hong Kong Chinese immigrant parents in Toronto to interrogate their values and
      assumptions about homosexuality. In particular, we illustrate how we use
      storytelling to create a liminal space whereby the narrators and listeners
      collaborate to create counter-discourses that challenge social domination and
      exclusion. We then discuss the implications of using a critical dialogical
      approach to integrate anti-homophobia efforts in community parenting programmes.

PMID- 23140181
TI  - Inhibition of the ecto-beta subunit of F1F0-ATPase inhibits proliferation and
      induces apoptosis in acute myeloid leukemia cell lines.
AB  - BACKGROUND: Leukemia, a heterogeneous clonal disorder of hematopoietic progenitor
      cells, presents a world-wide health problem, especially in childhood. F1F0
      ATPase, an inner mitochondrial enzyme, is expressed on the plasma membrane of
      tumor cells, and its inhibition induces both anti-angiogenic and anti-tumorigenic
      activity. METHODS: Monoclonal Antibody (McAb) against ATPase was produced by
      polyethylene glycol-mediated fusions and screened by ELISA. Proliferation, cell
      cycle and apoptosis of cells were analyzed when the surface ATPase of cells was
      blockaded with McAb. RESULTS: We detected cell-membrane expression of the F1F0
      ATPase beta subunit on 0.1% to 56% of the 11 cell lines derived from leukemia,
      including acute myeloid leukemia (AML). We produced a monoclonal antibody,
      McAb7E10, which recognizes both the native and recombinant ATPase beta subunit,
      with a dissociation constant (KD) of 3.26E-10. We demonstrate that McAb7E10 binds
      to ATPase at the cell surface, where it is able to inhibit ATP synthesis.
      McAb7E10 significantly inhibited proliferation of AML cell lines in vitro: the
      relative inhibitory rates of 50 MUg/mL McAb7E10 treated MV4-11and HL-60 cells
      were 69.6% and 81.9% respectively. Cell cycle analysis indicated that McAb7E10
      significantly induced apoptosis in MV4-11 and HL-60 cells: the relative rates of
      apoptosis in 5, 10 and 50ug/mL McAb7E10 treated MV4-11 cells was 3.6 +/- 0.83%,
      8.4 +/- 1.69% and 17.3 +/- 2.56% compared to 1.5% +/- 0.85% in mouse IgG treated
      cells (p < 0.01). The relative rate of apoptosis in 5, 10 and 50ug/mL McAb7E10
      treated HL-60 cells was 5.5 +/- 2.37%, 11.3 +/- 3.62% and 19.9 +/- 3.31% compared
      to 1.56% +/- 0.97% in mouse IgG treated cells (p < 0.01). Annexin V staining
      demonstrated that the relative apoptotic rates in 50 MUg/mL McAb7E10 treated MV4
      11 and HL-60 cells were 50.5% +/- 7.04% and 32.9% +/- 4.52%, respectively,
      significantly higher than IgG control antibody treated cells were 21.9% +/- 3.11%
      and 15.3% +/- 3.95%, p < 0.01. CONCLUSIONS: These findings indicate that ectopic
      expression of ATPase beta subunit may be a tumor-associated antigen in
      hematological malignancies. The F1F0 ATPase beta subunit provides a potential
      target for immunotherapy in AML and hematological malignancies.

PMID- 23140183
TI  - Errors in palliative care: kinds, causes, and consequences: a pilot survey of
      experiences and attitudes of palliative care professionals.
AB  - BACKGROUND: Medical errors have recently been recognized as a relevant concern in
      public health, and increasing research efforts have been made to find ways of
      improving patient safety. In palliative care, however, studies on errors are
      scant. OBJECTIVE: Our aim was to gather pilot data concerning experiences and
      attitudes of palliative care professionals on this topic. METHODS: We developed a
      questionnaire, which consists of questions on relevance, estimated frequency,
      kinds and severity of errors, their causes and consequences, and the way
      palliative care professionals handle them. The questionnaire was sent to all
      specialist palliative care institutions in the region of Bavaria, Germany (n=168;
      inhabitants 12.5 million) reaching a response rate of 42% (n=70). RESULTS: Errors
      in palliative care were regarded as a highly relevant problem (median 8 on a 10
      point numeric rating scale). Most respondents experienced a moderate frequency of
      errors (1-10 per 100 patients). Errors in communication were estimated to be more
      common than those in symptom control. The causes most often mentioned were
      deficits in communication or organization. Moral and psychological problems for
      the person committing the error were seen as more frequent than consequences for
      the patient. Ninety percent of respondents declared that they disclose errors to
      the harmed patient. For 78% of the professionals, the issue was not a part of
      their professional training. CONCLUSION: Professionals acknowledge errors-in
      particular errors in communication-to be a common and relevant problem in
      palliative care, one that has, however, been neglected in training and research.

PMID- 23140184
TI  - Impact of hospital case volume on quality of end-of-life care in terminal cancer
      patients.
AB  - BACKGROUND: Quality of end-of-life (EOL) care is gaining increasing attention.
      However, the relationship between hospital case volume and performance of
      benchmark quality indicators is not well characterized. The aim of this study was
      to determine whether hospital case volume affects EOL care for terminal cancer
      patients. METHODS: We conducted a retrospective cross-sectional study using
      claims data of patients who died of cancer at acute-care hospitals in Kyoto
      prefecture, Japan, between March 2009 and May 2010. Hospitals were grouped into
      tertiles based on the number of terminal cancer cases. We used multilevel
      logistic regression models to examine the association of the following quality
      indicators with the tertiles: opioid use during the last 2 months of life
      (indicating good quality of care), provision of intensive care unit (ICU) service
      or life-sustaining treatments during the last month of life (poor quality), and
      chemotherapy during the last month of life (poor quality). RESULTS: The final
      sample for analysis consisted of 3294 decedents from 88 hospitals. Significant
      associations between hospital case volume and quality of EOL care were identified
      after adjusting for patient and hospital characteristics. Small- and medium
      volume hospitals were found to be less likely to administer opioids, and medium
      volume hospitals were more likely to provide ICU service or life-sustaining
      treatments when compared with large-volume hospitals. No significant association
      between chemotherapy use and case volume was observed. CONCLUSIONS: The results
      showed that the case volume of terminally ill cancer patients was associated with
      several aspects of quality of EOL care.

PMID- 23140185
TI  - Atorvastatin calcium plus amlodipine for the treatment of hypertension.
AB  - INTRODUCTION: Hypertension (HTN) and dyslipemia (DYL) are two of the major
      modifiable cardiovascular (CV) risk factors, determinants in the development of
      cerebrovascular and coronary heart disease (CHD). Many patients have both risk
      factors which increase their total CV risk compared with patients with only one
      risk factor. Treatment guideline recommendations are poorly implemented in real
      practice, in part due to numerous and complicated drug regimes which hamper
      patient's adherence. AREAS COVERED: In this article the authors describe the
      first combined fixed-dose pill of an antihypertensive and a lipid-lowering agent,
      the single-pill combination of amlodipine besylate and atorvastatin calcium
      (SPAA). They summarize the pharmacokinetic and pharmacodynamic properties of both
      compounds and the main randomized clinical studies, as well as real-world
      observational studies, made with the new combined formulation. EXPERT OPINION:
      The use of the single-pill amlodipine and atorvastatin is an adequate option for
      the clinician to treat hypertensive patients with DYL or high CV risk burden,
      with proven efficacy, tolerability, cost-effectiveness, and the advantage of
      improving patient treatment compliance.

PMID- 23140187
TI  - Thiacalixarene covalently functionalized multiwalled carbon nanotubes as
      chemically modified electrode material for detection of ultratrace Pb2+ ions.
AB  - This paper presents the preparation of novel thiacalixarene (TCA) covalently
      functionalized multiwalled carbon nanotubes (MWCNTs) and an enhanced differential
      pulse anodic stripping voltammetric procedure for the determination of trace
      amounts of Pb(2+) ions, which relies on the selective accumulation of the metals
      at a TCA-MWCNT-modified glassy carbon electrode. Through a combination of
      thiacalixerene's excellent selective recognition and the outstanding electronic
      properties of MWCNTs, this electrode material shows excellent selectivity and
      high sensitivity for electrochemical detection of Pb(2+) ions. The stripping
      response is highly linear (R = 0.999) over a Pb(2+) concentration range of 2 *
      10(-10) to 1 * 10(-8) mol/L, and the limit of detection is 4 * 10(-11) mol/L.
      Furthermore, the determination of Pb(2+) (10(-7) mol/L) in the presence of an
      equal amount of interfering Sn(2+) ions yielded well-separated signals. To
      understand the molecular interaction mechanism between the TCA molecules and
      metal ions (Pb(2+) and Sn(2+)), theoretical computations were performed. The
      results demonstrate that the Pb(2+)/Sn(2+) ions could stably adsorb onto the TCA
      molecules, and there is significant electron delocalization between Pb(2+)/Sn(2+)
      and sulfur atoms in the TCA molecule.

PMID- 23140188
TI  - Plasminogen receptors and their role in the pathogenesis of inflammatory,
      autoimmune and malignant disease.
AB  - Plasminogen is the proenzyme of plasmin, the key protease of the fibrinolytic
      system, but its role is not limited to fibrinolysis regulation. Plasminogen binds
      not only to fibrin, but also to different receptors on cell surfaces, including
      the heterotetrameric complex Annexin A2-S100A10, enolase-1, histone H2B and the
      plasminogen receptor Plg-R(KT) . These receptors localize plasmin generation to
      the cell surface and provide a broad spectrum of reactions including proteolytic
      activity, cell migration and recruitment as well as signaling pathway activation.
      These plasminogen-binding proteins are involved in both physiologic and
      pathologic processes such as inflammation, thrombosis and cancer. Thus,
      plasminogen is at the center of a complex tightly controlled and regulated system
      where plasminogen-binding proteins have a crucial role, suggesting new
      therapeutic and diagnostic strategies. This review will discuss currently
      available information on plasminogen receptors, particularly their mechanisms of
      action and their roles in inflammatory, autoimmune and malignant disease.

PMID- 23140186
TI  - Functional characterization of a tomato COBRA-like gene functioning in fruit
      development and ripening.
AB  - BACKGROUND: Extensive studies have demonstrated that the COBRA gene is critical
      for biosynthesis of cell wall constituents comprising structural tissues of
      roots, stalks, leaves and other vegetative organs, however, its role in fruit
      development and ripening remains largely unknown. RESULTS: We identified a tomato
      gene (SlCOBRA-like) homologous to Arabidopsis COBRA, and determined its role in
      fleshy fruit biology. The SlCOBRA-like gene is highly expressed in vegetative
      organs and in early fruit development, but its expression in fruit declines
      dramatically during ripening stages, implying a primary role in early fruit
      development. Fruit-specific suppression of SlCOBRA-like resulted in impaired cell
      wall integrity and up-regulation of genes encoding proteins involved in cell wall
      degradation during early fruit development. In contrast, fruit-specific
      overexpression of SlCOBRA-like resulted in increased wall thickness of fruit
      epidermal cells, more collenchymatous cells beneath the epidermis, elevated
      levels of cellulose and reduced pectin solubilization in the pericarp cells of
      red ripe fruits. Moreover, transgenic tomato fruits overexpressing SlCOBRA-like
      exhibited desirable early development phenotypes including enhanced firmness and
      a prolonged shelf life. CONCLUSIONS: Our results suggest that SlCOBRA-like plays
      an important role in fruit cell wall architecture and provides a potential
      genetic tool for extending the shelf life of tomato and potentially additional
      fruits.

PMID- 23140189
TI  - Ligand-based pharmacophore detection, screening of potential gliptins and docking
      studies to get effective antidiabetic agents.
AB  - Three-dimensional pharmacophore hypothesis was established based on a set of
      known DPP-IV inhibitor using PharmaGist software program understanding the
      essential structural features for DPP-IV inhibitor. The various marketed or under
      developmental status, potential gliptins have been opted to build a pharmacophore
      model, e.g. Sitagliptin (MK- 0431), Saxagliptin, Melogliptin, Linagliptin (BI
      1356), Dutogliptin, Carmegliptin, Alogliptin and Vildagliptin (LAF237).
      PharmaGist web based program is employed for pharmacophore development. Four
      points pharmacophore with the hydrogen bond acceptor (A), hydrophobic group (H),
      Spatial Features and aromatic rings (R) have been considered to develop
      pharmacophoric features by PharmaGist program. The best pharmacophore model
      bearing the Score 16.971, has been opted to screen on ZincPharmer database to
      derive the novel potential anti-diabetic ligands. The best pharmacophore bear
      various Pharmacophore features, including General Features 3, Spatial Features 1,
      Aromatic 1 and Acceptors 2. The PharmaGist employed algorithm to identify the
      best pharmacophores by computing multiple flexible alignments between the input
      ligands. The multiple alignments are generated by combining alignments pair-wise
      between one of the gliptin input ligands, which acts as pivot and the other
      gliptin as ligand. The resulting multiple alignments reveal spatial arrangements
      of consensus features shared by different subsets of input ligands. The best
      pharmacophore model has been derived using both pair-wise and multiple alignment
      methods, which have been weighted in Pharmacophore Generation process. The
      highest-scoring pharmacophore model has been selected as potential pharmacophore
      model. In conclusion, 3D structure search has been performed on the "ZincPharmer
      Database" to identify potential compounds that have been matched with the
      proposed pharmacophoric features. The 3D ZincPharmer Database has been matched
      with various thousands of Ligands hits. Those matches were screened through the
      RMSD and max hits per molecule. The physicochemical properties of various
      "ZincPharmer Database" screened ligands have been calculated by PaDELDescriptor
      software. The all "ZincPharmer Database" screened ligands have been filtered
      based on the Lipinski's rule-of-five criteria (i.e. Molecular Weight < 500, H
      bond acceptor <= 10, H-bond donor <= 5, Log P <= 5) and were subjected to
      molecular docking studies to get the potential antidiabetic ligands. We have
      found various substituted as potential antidiabetic ligands, which can be used
      for further development of antidiabetic agents. In the present research work, we
      have covered rational of DPP-IV inhibitor based on Ligand-Based Pharmacophore
      detection, which is validated via the Docking interaction studies as well as
      Maximal Common Substructure (MCS).

PMID- 23140190
TI  - One-pot, three-component synthesis of spirooxindoles catalyzed by ZnO nano-rods
      in solvent-free conditions.
AB  - Recyclable ZnO nano-rods catalyst as a most efficient and straightforward
      protocol for one-pot, three-component synthesis of spirooxindole derivatives at
      room temperature under solvent-free conditions in both reaction media and work-up
      procedure is described. This method is of great value because of its
      environmentally benign character, easy handling, high yields, convenient
      operation (grinding), room temperature, low cost and green.

PMID- 23140191
TI  - Microwave-assisted multicomponent reactions of alkyl bromides: synthesis of
      thiophene derivatives.
AB  - A series of thiophene derivatives were synthesized via one-pot multicomponent
      reactions of alkyl bromides, aroyl or alkanoyl isothiocyanates, 1,3-dicarbonyl
      compounds and secondary amines under microwave irradiation at 80 degrees C.
      Particularly valuable features of this method include high yields of products,
      broad substrate scope, short reaction time and straightforward procedure.

PMID- 23140192
TI  - Expeditious solvent-free synthesis of chromene derivatives via three-component
      reactions of N-nucleophiles.
AB  - Multicomponent reactions involving 4-hydroxycumarine, activated acetylenic
      compounds and N-nucleophiles under solvent-free conditions were investigated. The
      reactions could also be extended to quinoline or CH-acides. Substituted chromen
      could be obtained from this routine, which may have potential applications in
      drugs fields.

PMID- 23140193
TI  - Photoresponsive capture and release of lectins in multilamellar complexes.
AB  - The development of triggered release systems for delivery of peptides and
      proteins is critical to the success of biological drug therapies. In this paper
      we describe a dynamic supramolecular system able to capture and release proteins
      in response to light. The ternary system self-assembles in a dilute aqueous
      solution of three components: vesicles of amphiphilic cyclodextrin host,
      noncovalent cross-linkers with an azobenzene and a carbohydrate moiety, and
      lectins. The cross-linkers form inclusion complexes with the host vesicles,
      provided the azobenzene is in the trans state. The formation of a ternary complex
      with lectins requires a high density of cross-linkers on the surface of vesicles.
      The key innovation in this system is a photoinduced switch from a multivalent,
      high-affinity state that captures protein to a monovalent, low-affinity state
      that releases protein. By using isothermal titration calorimetry, dynamic light
      scattering, UV/vis spectroscopy, and cryogenic transmission electron microscopy,
      we demonstrate that photoinduced capture and release of lectins in dense
      multilamellar complexes is highly efficient, highly selective, and fully
      reversible.

PMID- 23140194
TI  - Electron transfer mechanism in organometallic molecules studied by subpicosecond
      extended X-ray absorption fine structure spectroscopy.
AB  - The mechanism responsible for the redox reaction of [Co(III)(en)3]Ac3 to Co(II)
      complex has been determined to be intramolecular electron transfer. It was
      measured in real time by means of subpicosecond extended X-ray absorption fine
      structure spectra, EXAFS, and optical experiments and supported by density
      functional theory calculations. The proposed mechanism is based on histograms of
      bond length changes of the transient structures measured as a function of time,
      with subpicosecond time and sub-Angstrom resolution and femtosecond transient
      spectra and kinetics after excitation with a 267 nm femtosecond pulse. Even
      though four Fe and Co complexes were excited in the charge transfer band and the
      photoinduced redox reaction proceeds with similar high redox quantum yield, the
      dominant electron operating mechanism differs: intramolecular for amine metal
      complexes and intermolecular for oxalate metal complexes. The ligand orientation
      degree of freedom and counterion effect are proposed to provide tentative
      explanation for the electron transfer mechanism.

PMID- 23140195
TI  - Emergency medical dispatch codes association with emergency department outcomes.
AB  - BACKGROUND: Emergency medical dispatch systems are used to help categorize and
      prioritize emergency medical services (EMS) resources for requests for
      assistance. OBJECTIVE: We examined whether a subset of Medical Priority Dispatch
      System (MPDS) codes could predict patient outcomes (emergency department [ED]
      discharge versus hospital admission/ED death). METHODS: This retrospective
      observational cohort study analyzed requests for EMS through a single public
      safety answering point (PSAP) serving a mixed urban, suburban, and rural
      community over one year. Probabilistic matching was used to link subjects.
      Descriptive statistics, 95% confidence intervals (CIs), and logistic regression
      were calculated for the 107 codes and code groupings (9E vs. 9E1, 9E2, etc.) that
      were used 50 or more times during the study period. RESULTS: Ninety percent of
      PSAP records were matched to EMS records and 84% of EMS records were matched to
      ED data, resulting in 26,846 subjects with complete records. The average age of
      the cohort was 46.2 years (standard deviation [SD] 24.8); 54% were female. Of the
      transported patients, 70% were discharged from the ED, with nine dispatch codes
      demonstrating a 90% or greater predictive power. Three code groupings had more
      than 60% predictive power for admission/death. Subjects aged 65 years and older
      were found to be at increased risk for admission/death in 33 dispatch codes (odds
      ratio [OR] 2.0 [95% confidence interval 1.3-3.0] to 19.6 [5.3-72.6]).
      CONCLUSIONS: A small subset (8% of codes; 7% by call volume) of MPDS codes were
      associated with greater than 90% predictive ability for ED discharge. Older
      adults are at increased risk for admission/death in a separate subset of MPDS
      codes, suggesting that age criteria may be useful to identify higher-acuity
      patients within the MPDS code. These findings could assist in
      prehospital/hospital resource management; however, future studies are needed to
      validate these findings for other EMS systems and to investigate possible
      strategies for improvements of emergency response systems.

PMID- 23140196
TI  - Context-specific, evidence-based planning for scale-up of family planning
      services to increase progress to MDG 5: health systems research.
AB  - BACKGROUND: Unmet need for family planning is responsible for 7.4 million
      disability-adjusted life years and 30% of the maternity-related disease burden.
      An estimated 35% of births are unintended and some 200 million couples state a
      desire to delay pregnancy or cease fertility but are not using contraception.
      Unmet need is higher among the poorest, lesser educated, rural residents and
      women under 19 years. The barriers to, and successful strategies for, satisfying
      all demand for modern contraceptives are heavily influenced by context.
      Successfully overcoming this to increase the uptake of family planning is
      estimated to reduce the risk of maternal death by up to 58% as well as contribute
      to poverty reduction, women's empowerment and educational, social and economic
      participation, national development and environmental protection. METHODS: To
      strengthen health systems for delivery of context-specific, equity-focused
      reproductive, maternal, newborn and child health services (RMNCH), the Investment
      Case study was applied in the Asia-Pacific region. Staff of local and central
      government and non-government organisations analysed data indicative of health
      service delivery through a supply-demand oriented framework to identify
      constraints to RMNCH scale-up. Planners developed contextualised strategies and
      the projected coverage increases were modelled for estimates of marginal impact
      on maternal mortality and costs over a five year period. RESULTS: In Indonesia,
      Philippines and Nepal the constraints behind incomplete coverage of family
      planning services included: weaknesses in commodities logistic management;
      geographical inaccessibility; limitations in health worker skills and numbers;
      legislation; and religious and cultural ideologies. Planned activities included:
      streamlining supply systems; establishment of Community Health Teams for
      integrated RMNCH services; local recruitment of staff and refresher training;
      task-shifting; and follow-up cards. Modelling showed varying marginal impact and
      costs for each setting with potential for significant reductions in the maternal
      mortality rate; up to 28% (25.1-30.7) over five years, costing up to a marginal
      USD 1.34 (1.32-1.35) per capita in the first year. CONCLUSION: Local health
      planners are in a prime position to devise feasible context-specific activities
      to overcome constraints and increase met need for family planning to accelerate
      progress towards MDG 5.

PMID- 23140197
TI  - Influence of hardening and surface modification of endourological wires on
      corrosion resistance.
AB  - Guide wires with suitable functional characteristics are of crucial importance
      for proper urological treatment. This study presents an analysis of the effect of
      work hardening taking place in the process of wire cold drawing and the effect of
      surface modification by means of electrochemical polishing and chemical
      passivation on the resistance of wires made of X10CrNi18-8 steel used in urology.
      Corrosion resistance was evaluated on the grounds of the registered anodic
      polarisation curves by means of potentiodynamic method. The tests were made in
      solution simulating human urine. Anodic polarisation curves were presented for
      selected wire diameters. Mechanical properties were tested in a static uniaxial
      tensile test. The course of flow curve as well as mathematical form of flow
      stress function were determined. Curves presenting the relation of polarisation
      resistance as a function of strain applied in the drawing process are given. The
      tests carried out show that surface modification by means of electrochemical
      polishing and then chemical passivation of wires used in endourological treatment
      is fundamental.

PMID- 23140198
TI  - A blinded study of bone marrow examinations in patients with primary immune
      thrombocytopenia.
AB  - OBJECTIVE: The role of bone marrow examinations in patients with primary immune
      thrombocytopenia (ITP) is uncertain. The objectives of this study were to
      determine the inter-rater reliability of bone marrow examinations and to identify
      distinguishing morphological features of ITP bone marrows under controlled
      conditions. METHODS: Histological slides of bone marrow biopsy specimens and
      aspirates from 32 adult patients with severe primary ITP who had failed a median
      of two treatments, and 51 non-thrombocytopenic controls were retrieved from
      hospital archives. Slides were arranged in random order in a slide box and coded.
      Blinded to the diagnosis and platelet counts, three independent
      hematopathologists were asked to identify the ITP bone marrows and to evaluate
      megakaryocyte number, morphology, and distribution. RESULTS: Overall chance
      corrected agreement on ITP classification among the three raters was poor [kappa
      (kappa) = 0.30; 95% confidence interval 0.22-0.38]. Raters were generally unable
      to correctly identify the ITP bone marrows from controls. Increased number of
      megakaryocytes, while an uncommon finding, was more frequent among ITP patients
      compared with controls (6/32, 18.8%; vs. 2/51, 3.9%; P = 0.05), and abnormal
      megakaryocyte morphology often led individual raters to reach a diagnosis of ITP.
      Overall sensitivity and specificity of bone marrow examinations were 24% and 90%,
      respectively. CONCLUSIONS: This study confirms methodologically that bone marrow
      examinations are unreliable and frequently non-diagnostic in ITP. Thus, they are
      not useful for patients with typical disease. Rare subsets of patients with
      severe ITP demonstrated unique features such as increased number of
      megakaryocytes.

PMID- 23140199
TI  - Arthroscopic resection of multiple ossifying tumors in the infrapatellar fat pad.
AB  - A 49 year-old male visited a nearby clinic five years back with a complaint of
      pain in the right knee during exercise. Plain radiographs revealed absence of any
      anomalies. He began to feel a lumpy mass in his right knee two years back. The
      pain worsened, on imaging, an anomaly was identified in the infrapatellar fat pad
      of his right knee, and he was subsequently referred to our department where he
      was hospitalized. On examination, a mass extending on either side of the patellar
      tendon was identified along with rigid tenderness in that area. The knee's range
      of motion was 0degrees-130degrees, and knee flexion was accompanied by pain. The
      results of blood tests were normal. A plain radiograph of the knee revealed
      multiple ossifying tumors at a site consistent with the infrapatellar fat pad. T1
      weighted MRI exhibited low-signal intensity, while T2-weighted MRI exhibited a
      mosaic-shaped tumor. We performed arthroscopic surgery to excise the tumor. The
      patient resumed work shortly after surgery and did not experience any pain during
      the two year postoperative observation period. The joint's range of motion
      improved to the extent that it was comparable with that of the left knee. No
      recurrence was observed on radiographic examination. In past studies, resection
      of similar tumors has been performed with an arthrotomy; however, we performed
      arthroscopic resection on our patient, who demonstrated a quick improvement in
      symptoms and range of motion after surgery. We believe that arthroscopic surgery
      is a feasible option to consider while treating such cases.

PMID- 23140201
TI  - Moving forward by looking back: reflecting on a decade of CDC's work in sexual
      violence prevention, 2000-2010.
AB  - In 2011, the Division of Violence Prevention (DVP) within CDC's Injury Center
      engaged an external panel of experts to review and evaluate its research and
      programmatic portfolio for sexual violence (SV) prevention from 2000 to 2010.
      This article summarizes findings from the review by highlighting DVP's key
      activities and accomplishments during this period and identifying remaining gaps
      in the field and future directions for SV prevention. DVP's SV prevention work in
      the 2000s included (1) raising the profile of SV as a public health problem, (2)
      shifting the field toward a focus on the primary prevention of SV perpetration,
      and (3) applying the public health model to SV research and programmatic
      activities. The panel recommended that DVP continue to draw attention to the
      importance of sexual violence prevention as a public health issue, build on prior
      investments in the Rape Prevention and Education Program, support high-quality
      surveillance and research activities, and enhance communication to improve the
      link between research and practice. Current DVP projects and priorities provide a
      foundation to actively address these recommendations. In addition, DVP continues
      to provide leadership and guidance to the research and practice fields, with the
      goal of achieving significant reductions in SV perpetration and allowing
      individuals to live to their full potential.

PMID- 23140202
TI  - Facilitating the career and leadership development of women: a potent new
      research tool.

PMID- 23140205
TI  - Lamotrigine  (Lamictal IR) for the treatment of bipolar disorder.
AB  - INTRODUCTION: Over the past decade the use of lamotrigine in bipolar disorder has
      increased. However, the evidence base suggests a more limited role for
      lamotrigine as part of an overall treatment regimen in bipolar disorder. AREAS
      COVERED: We reviewed publications of randomized clinical trials of lamotrigine,
      emphasizing studies in bipolar disorder. The low burden of adverse effects with
      lamotrigine has been confirmed in these studies. Its lack of benefit in acute
      mania is established. Despite modest benefits for a subset of depressive episodes
      in bipolar disorder, it was not superior to placebo in well-designed studies. As
      monotherapy, in randomized, blinded trials in rapid cycling bipolar disorder it
      was not superior to placebo. Its role in maintenance treatment is relatively well
      established as one component of combination therapy, with evidence for benefits
      when combined with lithium or valproate. Combination regimens including
      lamotrigine appear to be superior to monotherapy. Monotherapy utilization of
      lamotrigine for maintenance treatment is not supported by these studies. EXPERT
      OPINION: Lamotrigine has benefits in bipolar disorder management principally as a
      component of combination treatment which includes a mood stabilizer. The utility
      of lamotrigine in acute bipolar depression and major depressive disorder is
      modest.

PMID- 23140203
TI  - Osteoporosis healthcare disparities in postmenopausal women.
AB  - BACKGROUND: Previous studies in referral populations have shown that fewer
      African American women complete dual-energy x-ray absorptiometry (DXA) screening
      and are prescribed medications for osteoporosis. This study examines if these
      disparities exist in primary care practices. METHODS: Of 4748 eligible women >=60
      years of age in primary care practices, we randomly selected 500 African American
      and 500 Caucasian women. We compared the DXA screening referral rate and results,
      follow-up rate, and medication prescribing for low bone mineral density (BMD)
      between African American and Caucasian women and analyzed provider demographics.
      We used logistic regression analysis to control confounding variables, such as
      age and BMI. RESULTS: Among the initial 1000 women, only 29.8% African American
      Women were referred to DXA compared to 38.4% Caucasian women (p<0.05), and 20.8%
      African American vs. 27.0% Caucasian (p<0.05) women completed the test. Among
      women with a diagnosis of osteoporosis, African Americans were less likely to
      receive medication (79.6% vs. 89.2%, p<0.05), without a difference in follow-up
      visit pattern between races. Female providers were more likely to refer women for
      DXA (27.7%) than male providers (21.7%) (p=0.035), and this gender difference in
      referral was more pronounced for African American patients. CONCLUSIONS: Not
      enough eligible women are being screened and treated for osteoporosis in primary
      care. Even fewer African American women receive DXA screenings and are treated
      for osteoporosis. Controlling for age and BMI attenuated but did not eliminate
      the difference. Female providers were more likely than male providers to refer
      women for DXA.

PMID- 23140206
TI  - Antioxidant and phytochemical properties of Carpobrotus edulis (L.) bolus leaf
      used for the management of common infections in HIV/AIDS patients in Eastern Cape
      Province.
AB  - BACKGROUND: Carpobrotus edulis (Mesembryanthemaceae), also known as igcukuma in
      Xhosa language is a medicinal plant used by the traditional healers to treat
      common infections in HIV/AIDS patients. Based on this information, we researched
      on the plant phytoconstituents, as well as its inhibitory effect using aqueous
      and three different organic solvent extracts in order to justify its therapeutic
      usage. METHODS: Antioxidant activity of the extracts were investigated
      spectrophotometrically against 1,1- diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino
      bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) diammonium salt, hydrogen
      peroxide (H2O2), nitric oxide (NO), and ferric reducing power, Total phenols,
      flavonoids, flavonols, proanthocyanidins, tannins, alkaloids and saponins were
      also determined using the standard methods. RESULTS: Quantitative phytochemical
      analysis of the four solvent extracts revealed a high percentage of phenolics
      (55.7 +/- 0.404%) in the acetone extract, with appreciable amount of
      proanthocyanidins (86.9 +/- 0.005%) and alkaloids (4.5 +/- 0.057%) in the aqueous
      extract, while tannin (48.9 +/- 0.28%) and saponin (4.5 +/- 0.262%) were major
      constituents of the ethanol extract. Flavonoids (0.12 +/- 0.05%) and flavonols
      (0.12 +/- 0.05%) were found at higher level in the hexane extract in comparison
      with the other extracts. The leaf extracts demonstrated strong hydrogen peroxide
      scavenging activity, with the exception of water and ethanol extracts. IC50
      values of the aqueous and ethanolic extract against DPPH, ABTS, and NO were 0.018
      and 0.016; 0.020 and 0.022; 0.05 and 0.023 mg/ml, respectively. The reducing
      power of the extract was found to be concentration dependent. CONCLUSION: The
      inhibitory effect of the extracts on free radicals may justify the traditional
      use of this plant in the management of common diseases in HIV/AIDs patients in
      Eastern Cape Province. Overall, both aqueous and ethanol were found to be the
      best solvents for antioxidant activity in C. edulis leaves.

PMID- 23140207
TI  - A novel method for purification of polymerizable tubulin with a high content of
      the acetylated isotype.
AB  - Tubulin can be acetylated/deacetylated on Lys40 of the alpha-subunit. Studies of
      the post-translational acetylation/deacetylation of tubulin using biochemical
      techniques require tubulin preparations that are enriched in AcTubulin
      (acetylated tubulin) and (for comparison) preparations lacking AcTubulin.
      Assembly-disassembly cycling of microtubules gives tubulin preparations that
      contain little or no AcTubulin. In the present study we demonstrated that this
      result is owing to the presence of high deacetylating activity in the extracts.
      This deacetylating activity in rat brain homogenates was inhibited by TSA
      (Trichostatin A) and tubacin, but not by nicotinamide, indicating that HDAC6
      (histone deacetylase 6) is involved. TSA showed no effect on microtubule
      polymerization or depolymerization. We utilized these properties of TSA to
      prevent deacetylation during the assembly-disassembly procedure. The effective
      inhibitory concentration of TSA was 3 MUM in the homogenate and 1 MUM in the
      subsequent cycling steps. By comparison with immunopurified AcTubulin, we
      estimated that ~64% of the tubulin molecules in the three cycled preparations
      were acetylated. The protein profiles of these tubulin preparations, as assessed
      by SDS/PAGE and Coomassie Blue staining, were identical to that of a preparation
      completely lacking AcTubulin obtained by assembly-disassembly cycles in the
      absence of TSA. The tyrosination state and in vitro assembly-disassembly kinetics
      were the same regardless of the degree of acetylation.

PMID- 23140208
TI  - Ultrasensitive sample quantitation via selected reaction monitoring using
      CITP/CZE-ESI-triple quadrupole MS.
AB  - We demonstrate the direct coupling of transient capillary
      isotachophoresis/capillary zone electrophoresis (CITP/CZE) with a high
      sensitivity triple quadrupole mass spectrometer operating in selected reaction
      monitoring (SRM) mode for sample quantitation. The capability of CITP/CZE for in
      situ sample enrichment and separation has been shown to significantly improve the
      analytical figures of merit. A linear dynamic range spanning 4 orders of
      magnitude was observed. An average signal-to-noise ratio (S/N) of 49.6 was
      observed for 50 amol of targeted peptide in the presence of a complex and much
      more abundant bovine serum albumin (BSA) digest. Correlation of variation (CV) of
      <10% for peak area was measured from triplicate sample analyses at 50 pM peptide
      concentration, showing good reproducibility of this online CITP/CZE-SRM mass
      spectrometry (MS) platform, and with limit of quantitation (LOQ) demonstrated to
      be well below 50 pM.

PMID- 23140209
TI  - An siRNA designing tool with a unique functional off-target filtering approach.
AB  - Investigations have revealed that silencing unwanted transcripts or off-targeting
      can induce false positive phenotype during RNA interference (RNAi)-based gene
      function study. But still the standard computational approaches towards small
      interfering RNA (siRNA) off-target minimization fall short in terms of addressing
      this false positive phenotype issue. Some of these off-targets may interfere with
      the biochemical pathway being investigated. It may also inadvertently target
      cell's metabolic pathways with unquantifiable consequences on the processes of
      user's interest. Here, we report the development of a siRNA selection tool that,
      for the first time, implements a functional off-target filtering that aims to
      minimize false positive phenotypes arising from inadvertent targets that are
      functionally similar or related to the direct target gene, along with a multi
      parametric classifier (support vector machine) for optimized selection of potent
      siRNAs. The functional off-target filtering minimizes the number of off-target
      genes which are functionally related to the direct target gene, i.e. involved in
      a common biological process and may have similar phenotype. A text-mining
      algorithm is used to find related biological processes associated with the direct
      target and each off-target transcript by comparison of the biological processes
      associated with these genes. It also gives the user a choice to select one or
      more off-targets that may be potentially more harmful, from a predicted off
      target gene list to be filtered out. Testing with huge set of biologically
      validated siRNAs from three different sources showed consistent good performance
      of our tool in terms of effective siRNA selection. It outperformed four potent
      siRNA selection algorithms of present day in terms of specificity in the
      selection of highly efficient siRNAs when compared on a common test set. A genome
      wide testing with potent siRNAs used in high-content screening confirmed
      validation of 2767 designed siRNAs in terms of phenotypic output. This tool
      presently supports siRNA designs for human genes and is freely available at
      http://gyanxet-beta.com . 

PMID- 23140210
TI  - Adherence to recommendations by infectious disease consultants and its influence
      on outcomes of intravenous antibiotic-treated hospitalized patients.
AB  - BACKGROUND: Consultation to infectious diseases specialists (ID), although not
      always performed by treating physicians, is part of hospital's daily practice.
      This study analyses adherence by treating physicians to written ID
      recommendations (inserted in clinical records) and its effect on outcome in
      hospitalized antibiotic-treated patients in a tertiary hospital in Spain.
      METHODS: A prospective, randomized, one-year study was performed. Patients
      receiving intravenous antimicrobial therapy prescribed by treating physicians for
      3 days were identified and randomised to intervention (insertion of written ID
      recommendations in clinical records) or non-intervention. Appropriateness of
      empirical treatments (by treating physicians) was classified as adequate,
      inadequate or unnecessary. In the intervention group, adherence to
      recommendations was classified as complete, partial or non-adherence. RESULTS: A
      total of 1173 patients were included, 602 in the non-intervention and 571 in the
      intervention group [199 (34.9%) showing complete adherence, 141 (24.7%) partial
      adherence and 231 (40.5%) non-adherence to recommendations]. In the multivariate
      analysis for adherence (R2 Cox=0.065, p=0.009), non-adherence was associated with
      prolonged antibiotic prophylaxis (p=0.004; OR=0.37, 95%CI=0.19-0.72). In the
      multivariate analysis for clinical failure (R2 Cox=0.126, p<0.001), Charlson
      index (p<0.001; OR=1.19, 95%CI=1.10-1.28), malnutrition (p=0.006; OR=2.00,
      95%CI=1.22-3.26), nosocomial infection (p<0.001; OR=4.12, 95%CI=2.27-7.48) and
      length of hospitalization (p<0.001; OR=1.01, 95%CI=1.01-1.02) were positively
      associated with failure, while complete adherence (p=0.001; OR=0.35, 95%CI=0.19
      0.64) and adequate initial treatment (p=0.010; OR=0.39, 95%CI=0.19-0.80) were
      negatively associated. CONCLUSIONS: Adherence to ID recommendations by treating
      physicians was associated with favorable outcome, in turn associated with
      shortened length of hospitalization. This may have important health-economic
      benefits and stimulates further investigation. TRIAL REGISTRATION: Current
      Controlled Trials ISRCTN83234896. http://www.controlled
      trials.com/isrctn/sample_documentation.asp.

PMID- 23140211
TI  - Dangerous liaisons: how the immune system deals with factor VIII.
AB  - Only a fraction of patients with hemophilia A develop a neutralizing antibody
      (inhibitor) response to therapeutic infusions of factor VIII. Our present
      understanding of the underlying causes of the immunogenicity of this protein is
      limited. In the past few years, insights into the uptake and processing of FVIII
      by antigen-presenting cells (APCs) have expanded significantly. Although the
      mechanism of endocytosis remains unclear, current data indicate that FVIII enters
      APCs via its C1 domain. Its subsequent processing within endolysosomes allows for
      presentation of a heterogeneous collection of FVIII-derived peptides on major
      histocompatibility complex (MHC) class II, and this peptide-MHC class II complex
      may then be recognized by cognate effector CD4(+) T cells, leading to anti-FVIII
      antibody production. Here we aim to summarize recent knowledge gained about FVIII
      processing and presentation by APCs, as well as the diversity of the FVIII
      specific T-cell repertoire in mice and humans. Moreover, we discuss possible
      factors that can drive FVIII immunogenicity. We believe that increasing
      understanding of the immune recognition of FVIII and the cellular mechanisms of
      anti-FVIII antibody production will lead to novel therapeutic approaches to
      prevent inhibitor formation in patients with hemophilia A.

PMID- 23140212
TI  - In vitro experiment for verification of the tandem shunt valve system: a novel
      method for treating hydrocephalus by flexibly controlling cerebrospinal fluid
      flow and intracranial pressure.
AB  - OBJECT: The CSF shunt valve is a medical device whose main function is to
      regulate intracranial pressure and drain excess CSF. The authors have developed a
      new therapeutic method for treating hydrocephalus, namely the tandem shunt valve
      system, which has the potential of flexibly controlling the CSF flow rate and
      intracranial pressure in patients. METHODS: The properties of the tandem system
      were verified by performing in vitro experiments. An in vitro system with a
      manometer was built to measure pressure and flow rates of water in open systems
      using the Codman Hakim Programmable Valve and the Strata adjustable pressure
      programmable valve. A single valve and 2 single shunt valves connected in series
      (the tandem shunt valve system) were connected to the manometer to check the
      final pressure. RESULTS: Conventional single shunt valve systems require valve
      pressures to be set higher to slow down the CSF flow rate, which inevitably
      results in a higher final pressure. On the other hand, the tandem shunt valve
      system uses the combination of 2 valves to slow the CSF flow rate without
      increasing the final pressure. CONCLUSIONS: The authors succeeded in
      experimentally demonstrating in vitro results of tandem systems and their
      effectiveness by applying a model to show that the valve with the higher pressure
      setting determined the final pressure of the entire system and the flow rate
      became slower than single shunt valve systems.

PMID- 23140213
TI  - Long-term change in ventricular size following endoscopic third ventriculostomy
      for hydrocephalus due to tectal plate gliomas.
AB  - OBJECT: Endoscopic third ventriculostomy (ETV) is an alternative to shunt
      placement in children with hydrocephalus due to tectal plate gliomas (TPGs).
      However, controversy remains regarding the amount of ventricular size reduction
      that should be expected after ETV. This study investigates ventricular size
      change after ETV for TPGs. METHODS: Twenty-two children were identified from a 15
      year retrospective database of neuroendoscopic procedures performed at the
      authors' institution, Children's Hospital of Alabama, in patients with a minimum
      of 1 year of follow-up. Clinical outcomes, including the need for further CSF
      diversion and symptom resolution, were recorded. The frontal and occipital horn
      ratio (FOR) was measured on pre- and postoperative, 1-year, and last follow-up
      imaging studies. RESULTS: In 17 (77%) of 22 children no additional procedure for
      CSF diversion was required. Of those in whom CSF diversion failed, 4 underwent
      successful repeat ETV and 1 required shunt replacement. Therefore, in 21 (96%) of
      22 patients, CSF diversion was accomplished with ETV. Preoperative and
      postoperative imaging was available for 18 (82%) of 22 patients. The FOR
      decreased in 89% of children who underwent ETV. The FOR progressively decreased
      1.7%, 11.2%, and 12.7% on the initial postoperative, 1-year, and last follow-up
      images, respectively. The mean radiological follow-up duration for 18 patients
      was 5.4 years. When ETV failed, the FOR increased at the time of failure in all
      patients. Failure occurred 1.6 years after initial ETV on average. The mean
      clinical follow-up period for all 22 patients was 5.3 years. In all cases
      clinical improvement was demonstrated at the last follow-up. CONCLUSIONS:
      Endoscopic third ventriculostomy successfully treated hydrocephalus in the
      extended follow-up period of patients with TPGs. The most significant reduction
      in ventricular size was observed at the the 1-year followup, with only modest
      reduction thereafter.

PMID- 23140214
TI  - Ventral spinal cerebrospinal fluid leak as the cause of persistent post-dural
      puncture headache in children.
AB  - Headache occurs after dural puncture in about 1%-25% of children who undergo the
      procedure-a rate similar to that seen in adults. Persistence of post-dural
      puncture headache in spite of bed rest, increased fluid intake, and epidural
      blood patch treatment, however, is rare. The authors reviewed the medical records
      and imaging studies of all patients 19 years of age or younger who they evaluated
      between 2001 and 2010 for intracranial hypotension, and they identified 8
      children who had persistent post-dural puncture headache despite maximal medical
      treatment and placement of epidural blood patches. A CSF leak could be
      demonstrated radiologically and treated surgically in 3 of these patients, and
      the authors report these 3 cases.   The patients were 2 girls (ages 14 and 16
      years) who had undergone lumbar puncture for evaluation of headache and fever and
      1 boy (age 13 years) who had undergone placement of a lumboperitoneal shunt using
      a Tuohy needle for treatment of pseudotumor cerebri. The boy also had undergone a
      laminectomy and exploration of the posterior dural sac, but no CSF leak could be
      identified. All 3 patients presented with new-onset orthostatic headaches, and in
      all 3 cases MRI demonstrated a large ventral lumbar or thoracolumbar CSF
      collection. Conventional myelography or digital subtraction myelography revealed
      a ventral dural defect at L2-3 requiring surgical repair. Through a posterior
      transdural approach, the dural defect was repaired using 6-0 Prolene sutures and
      a dural substitute. Postoperative recovery was uneventful, with complete
      resolution of orthostatic headache and of the ventral cerebrospinal fluid leak on
      MRI.   The authors conclude that persistent postdural puncture headache requiring
      surgical repair is rare in children. They note that the CSF leak may be located
      ventrally and may require conventional or digital subtraction myelography for
      exact localization and that transdural repair is safe and effective in
      eliminating the headaches.

PMID- 23140215
TI  - Study of fetal and postnatal morphological development of the brain sulci.
AB  - OBJECT: The surface of the developing fetal brain undergoes significant
      morphological changes during fetal growth. The purpose of this study was to
      evaluate the morphological development of the brain sulci from the fetal to the
      early postnatal period. METHODS: Two hundred fourteen brain hemispheres from 107
      human brain specimens were examined to evaluate the timing of sulcal formation,
      from its appearance to its complete development. These brains were obtained from
      cadavers ranging in age from 12 weeks of gestation to 8 months of postnatal life.
      RESULTS: The order of appearance of the cerebral sulci, and the number and
      percentages of specimens found in this study were as follows: longitudinal
      cerebral fissure at 12 weeks (10/10, 100%); callosal sulcus at 12 weeks (10/10,
      100%); hippocampal sulcus at 15 weeks (7/10, 70%); lateral sulcus at 17 weeks
      (20/22, 90.9%); circular insular sulcus at 17 weeks (18/22, 81.8%); olfactory
      sulcus at 17 weeks (18/22, 81.8%); calcarine sulcus at 17 weeks (14/22, 63.6%);
      parietooccipital sulcus at 17 weeks (11/22, 50%); cingulate sulcus at 19 weeks
      (16/20, 80%); central sulcus at 21 weeks (22/38, 57.9%); orbital sulcus at 22
      weeks (9/16, 56.2%); lunate sulcus at 24 +/- 2 weeks (12/16, 75%); collateral
      sulcus at 24 +/- 2 weeks (8/16, 50%); superior frontal sulcus at 25 +/- 2 weeks
      (5/6, 83.3%); rhinal sulcus at 25 +/- 2 weeks (3/6, 50%); precentral sulcus at 26
      +/- 3 weeks (2/4, 50%); postcentral sulcus at 26 +/- 3 weeks (2/4, 50%); superior
      temporal sulcus at 26 +/- 3 weeks (2/4, 50%); central insular sulcus at 29 +/- 2
      weeks (4/4, 100%); intraparietal sulcus at 29 +/- 2 weeks (2/4, 50%);
      paraolfactory sulcus at 29 +/- 2 weeks (2/4, 50%); inferior frontal sulcus at 30
      +/- 3 weeks (2/4, 50%); transverse occipital sulcus at 30 +/- 3 weeks (2/4, 50%);
      occipitotemporal sulcus at 30 +/- 3 weeks (2/4, 50%); marginal branch of the
      cingulate sulcus at 30 +/- 3 weeks (2/4, 50%); paracentral sulcus at 30 +/- 3
      weeks (2/4, 50%); subparietal sulcus at 30 +/- 3 weeks (2/4, 50%); inferior
      temporal sulcus at 31 +/- 3 weeks (3/6, 50%); transverse temporal sulcus at 33 +/
      3 weeks (6/8, 75%); and secondary sulcus at 38 +/- 3 weeks (2/4, 50%).
      CONCLUSIONS: The brain is subjected to considerable morphological changes
      throughout gestation. During fetal brain development the cortex begins to fold
      in, thereby increasing the cortical surface. All primary sulci are formed during
      fetal life. The appearance of each sulcus follows a characteristic timing
      pattern, which may be used as one of the reliable guides pertinent to gestational
      age and normal fetal development.

PMID- 23140216
TI  - Solitary fibrous tumor of the scalp in a child.
AB  - Solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms that arise most
      commonly in the pleura but have been increasingly reported in extrapleural sites.
      The authors report the case of an SFT of the scalp that manifested as an
      enlarging scalp mass in a 2-year-old boy. The mass was surgically excised.
      Histological examination showed it to be composed of fusiform cells of variable
      cellularity with a central hyalinization zone. Immunohistochemical staining was
      positive for CD34 and negative for smooth muscle actin, S100 protein, desmin, and
      h-caldesmon. On 1-year follow-up, there was no recurrence of the mass. This case
      presented some diagnostic difficulty because of the wide range of possible
      diagnoses for a pediatric scalp mass; however, the distinct immunohistochemical
      profile helped to eliminate other more frequent fibrous tumors of the scalp.  
      The behavior of scalp SFTs is usually benign, but their course can be
      unpredictable, and recognition of these lesions is essential.

PMID- 23140217
TI  - Coexistence of dermal sinus tract, dermoid cyst, and encephalocele in a patient
      presenting with nasal cellulitis.
AB  - Dermoid cysts, encephaloceles, and dermal sinus tracts represent abnormalities
      that develop during the process of embryogenesis. The elucidation of the precise
      timing of formation for these malformations has remained elusive at the molecular
      level of study. Yet, clinical experience has demonstrated that these
      malformations do not all occur in the same patient, suggesting a shared pathway
      that goes awry at distinct points for different patients, resulting in 1 of the 3
      malformations. Herein the authors describe a case in which all 3 malformations
      were present in a single patient. This is the first description in the English
      literature of a sincipital encephalocele occurring with a dermoid cyst and a
      dermal sinus tract.

PMID- 23140218
TI  - Temperature-dependent dynamical transitions of different classes of amino acid
      residue in a globular protein.
AB  - The temperature dependences of the nanosecond dynamics of different chemical
      classes of amino acid residue have been analyzed by combining elastic incoherent
      neutron scattering experiments with molecular dynamics simulations on cytochrome
      P450cam. At T = 100-160 K, anharmonic motion in hydrophobic and aromatic residues
      is activated, whereas hydrophilic residue motions are suppressed because of
      hydrogen-bonding interactions. In contrast, at T = 180-220 K, water-activated
      jumps of hydrophilic side chains, which are strongly coupled to the relaxation
      rates of the hydrogen bonds they form with hydration water, become apparent.
      Thus, with increasing temperature, first the hydrophobic core awakens, followed
      by the hydrophilic surface.

PMID- 23140219
TI  - Effect of immobilized amines on the sorption properties of solid materials:
      impregnation versus grafting.
AB  - The underlying mechanism of the adsorption process in functionalized materials is
      not yet fully understood. This incomplete understanding limits the possibility of
      designing optimal adsorbent materials for different applications. Hence, the
      availability of complementary methods to advance this field is of great interest.
      We present here results concerning the adsorption of CO(2) in amine
      functionalized silica materials by Monte Carlo simulations, providing new
      insights into the capture process. Two different mechanisms of functionalization
      are compared: impregnation (a physical mixture of the amine and the support) and
      grafting (a chemical bond is formed between the amine and the support). We
      evaluate in this work a model of MCM-41 for N(2) and CO(2) adsorption with
      varying degrees of density of the functionalized chains. The results indicate
      that the mobility of the impregnated chains allows the creation of a network of
      microcavities, which enhance the low-pressure adsorption capabilities of these
      materials. Molecular simulations allow us to study in detail the conformational
      changes in the functionalized chains during the adsorption process. Materials
      functionalized densely by grafting undergo a change in the preferential
      orientation of the chains, which allows the adsorption of additional molecules
      close to the surface of the support. The adsorption of gas molecules close to the
      pore surface is usually the most energetically favorable configuration; however,
      for densely grafted materials the adsorption close to the surface occurs only at
      pressures large enough to provide energy to displace the functionalized chains.

PMID- 23140220
TI  - Evaluation of nanoparticle tracking analysis for total virus particle
      determination.
AB  - The NanoSight LM10 with Nanoparticle tracking analysis (NTA) software was
      evaluated for the quantification of latex particles, adenovirus 5, and influenza
      virus. The inter-day variability was determined by measuring the same sample over
      several consecutive days and the method's accuracy was demonstrated by using
      known concentrations of the subject particles. NTA analysis was also used to
      quantify chromatographic fractions of adenovirus and influenza virus after
      purification on a CIM monolithic column. NTA results were compared and evaluated
      against hemagglutination (HA) and end point dilution assay, determining total and
      infection virus particle number, respectively. The results demonstrated that
      nanoparticle tracking analysis is a method for fast estimation of virus
      concentration in different samples. In addition, it can provide a better insight
      into the sample status, regarding the level of virus aggregation.

PMID- 23140221
TI  - Spectroscopic techniques in the study of human tissues and their components. Part
      I: IR spectroscopy.
AB  - Among the currently used methods of monitoring human tissues and their components
      many types of research are distinguished. These include spectroscopic techniques.
      The advantage of these techniques is the small amount of sample required, the
      rapid process of recording the spectra, and most importantly in the case of
      biological samples - preparation of tissues is not required. In this work,
      vibrational spectroscopy: ATR-FTIR and Raman spectroscopy will be used. Studies
      are carried out on tissues: tendons, blood vessels, skin, red blood cells and
      biological components: amino acids, proteins, DNA, plasma, and deposits.

PMID- 23140222
TI  - Survey of preferred guideline attributes: what helps to make guidelines more
      useful for emergency health practitioners?
AB  - BACKGROUND: Enhancing CPG acceptance and implementation can play a major role in
      the development and establishment of emergency medicine as a specialty in many
      parts of the world. A Guideline International Network special interest group
      established to support collaboration to improve uptake of clinical practice
      guidelines (CPGs) across the emergency care sector conducted an international
      survey to identify attributes of guideline likely to enhance their use. METHODS:
      A Web-based survey was undertaken to determine how CPGs were accessed, the
      preferred formats and attributes of guidelines, and familiarity with GRADE. The
      criteria used to identify preferred attributes of guidelines were adapted from
      the AGREE II Tool. RESULTS: Two hundred six responses were received from 31
      countries, 74/206 (36%) from the US, 28/206 (16%) from Canada, 17/206 (8%) from
      Australia and 15/206 (7%) from the UK. The majority of responses were from
      physicians (176/206, 85%) with 15/206 (7%) of responses from nurses and 9/206
      (4%) from pre-hospital emergency services personnel. The preferred format for
      guidelines was clinical protocols that incorporated recommendations into
      workflow, and the most preferred attribute of guidelines was the clear
      identification of key recommendations. The results also identified that within
      the group that responded to the question related to GRADE, 66% were unfamiliar
      with this system for summarizing evidence in relationship to recommendations.
      CONCLUSIONS: The findings provide the basis for further research to explore the
      most appropriate formats for guidelines or guidelines resources tailored to the
      needs of the emergency care providers.

PMID- 23140223
TI  - Probing ultrafast photochemistry of retinal proteins in the near-IR:
      bacteriorhodopsin and anabaena sensory rhodopsin vs retinal protonated Schiff
      base in solution.
AB  - Photochemistry of bacteriorhodopsin (bR), anabaena sensory rhodopsin (ASR), and
      all-trans retinal protonated Schiff base (RPSB) in ethanol is followed with
      femtosecond pump-hyperspectral near-IR (NIR) probe spectroscopy. This is the
      first systematic probing of retinal protein photochemistry in this spectral
      range. Stimulated emission of the proteins is demonstrated to extend deep into
      the NIR, and to decay on the same characteristic time scales previously
      determined by visible probing. No signs of a transient NIR absorption band above
      lambdapr > 1.3 MUm, which was recently reported and is verified here for the RPSB
      in solution, is observed in either protein. This discrepancy demonstrates that
      the protein surroundings change photochemical traits of the chromophore
      significantly, inducing changes either in the energies or couplings of
      photochemically relevant electronic excited states. In addition, low-frequency
      and heavily damped spectral modulations are observed in the NIR signals of all
      three systems up to 1.4 MUm. By background subtraction and Fourier analysis they
      are shown to resemble wave packet signatures in the visible, stemming from
      multiple vibrational modes and by analogy are assigned to torsional wave packets
      in the excited state of the retinal chromophore. Differences in the vibrational
      frequencies between the three samples and the said discrepancy in transient
      spectra are discussed in terms of opsin effects on the RPSB electronic structure.

PMID- 23140224
TI  - Hydrogen-supplemented drinking water, just soda or an elixir of life?

PMID- 23140226
TI  - Regulatory T cells in chronic lymphocytic leukemia: some progress and a bit of
      "tolerance" in understanding disease progression.

PMID- 23140227
TI  - Regenerative potential of decellularized porcine nucleus pulposus hydrogel
      scaffolds: stem cell differentiation, matrix remodeling, and biocompatibility
      studies.
AB  - Nucleus pulposus (NP) tissue regeneration has been proposed as an early stage
      interventional therapy to combat intervertebral disc degeneration. We have
      previously reported on the development and characterization of a novel biomimetic
      acellular porcine NP (APNP) hydrogel. Herein, we aimed to evaluate this material
      for use as a suitable scaffold for NP tissue regeneration. Human-adipose-derived
      stem cells (hADSCs) were cultured for 14 days on APNP hydrogels in chemically
      defined differentiation media and were analyzed for an NP-cell-like mRNA
      expression profile, evidence of hydrogel remodeling including hydrogel
      contraction measurements, extracellular matrix production, and compressive
      dynamic mechanical properties. The innate capacity of the hydrogel itself to
      induce stem cell differentiation was also examined via culture in media lacking
      soluble differentiation factors. Additionally, the in vivo biocompatibility of
      non-crosslinked and ethyldimethylaminopropyl carbodiimide/N-hydroxysuccinimide
      and pentagalloyl glucose crosslinked hydrogels was evaluated in a rat subdermal
      model. Results indicated that hADSCs expressed putative NP-cell-positive gene
      transcript markers when cultured on APNP hydrogels. Additionally,
      glycosaminoglycan and collagen content of hADSC-seeded hydrogels was
      significantly greater than nonseeded controls and cell-seeded hydrogels exhibited
      evidence of contraction and tissue inhibitors of metalloproteinase-1 production.
      The dynamic mechanical properties of the hADSC-seeded hydrogels increased with
      time in culture in comparison to noncell-seeded controls and approached values
      reported for native NP tissue. Immunohistochemical analysis of explants
      illustrated the presence of mononuclear cells, including macrophages and
      fibroblasts, as well as blood vessel infiltration and collagen deposition within
      the implant interstices after 4 weeks of implantation. Taken together, these
      results suggest that APNP hydrogels, in concert with autologous ADSCs, may serve
      as a suitable scaffold for NP tissue regeneration.

PMID- 23140228
TI  - Subcutaneous IFN-beta1a to treat relapsing-remitting multiple sclerosis.
AB  - Multiple sclerosis (MS) is the main nontraumatic cause of handicap in young
      adults. Immunomodulators and treatments limiting lymphocyte migration have been
      proven efficient to treat relapsing-remitting MS. Subcutaneous IFN-beta1a improve
      relapse rate and MRI parameters in a series of double-blind, placebo-controlled
      trials in relapsing-remitting MS patients. Similar results, and with a greater
      extent, were obtained when treating patients with a first demyelinating event
      suggestive of MS. Except for the rare liver toxicity, the drug is well tolerated
      and has no severe adverse reaction. When compared with intramuscular IFN-beta1a,
      both relapse rate and MRI parameters were modulated in favor of the subcutaneous
      administration. Although the effect of subcutaneous IFN-beta1a on disability
      progression is limited, the good tolerance profile together with the efficiency
      of the drug explain why this treatment, as well as the other interferons and
      glatiramer acetate, is a first-line therapy for relapsing-remitting MS.

PMID- 23140229
TI  - The role of synthetic biology for in situ resource utilization (ISRU).
AB  - A persistent presence in space can either be supported from Earth or generate the
      required resources for human survival from material already present in space, so
      called "in situ material." Likely, many of these resources such as water or
      oxygen can best be liberated from in situ material by conventional physical and
      chemical processes. However, there is one critical resource required for human
      life that can only be produced in quantity by biological processes: high-protein
      food. Here, recent data concerning the materials available on the Moon and common
      asteroid types is reviewed with regard to the necessary materials to support the
      production of food from material in situ to those environments. These materials
      and their suitability as feedstock for the biological production of food are
      reviewed in a broad and general way such that terminology that is often a barrier
      to understanding such material by interdisciplinary readers is avoided. The waste
      products available as in situ materials for feasibility studies on the
      International Space Station are also briefly discussed. The conclusion is that
      food production in space environments from in situ material proven to exist there
      is quite feasible.

PMID- 23140230
TI  - Improving primary care in British Columbia, Canada: evaluation of a peer-to-peer
      continuing education program for family physicians.
AB  - BACKGROUND: An innovative program, the Practice Support Program (PSP), for full
      service family physicians and their medical office assistants in primary care
      practices was recently introduced in British Columbia, Canada. The PSP was
      jointly approved by both government and physician groups, and is a dynamic,
      interactive, educational and supportive program that offers peer-to-peer training
      to physicians and their office staff. Topic areas range from clinical
      tools/skills to office management relevant to General Practitioner (GP) practices
      and "doable in real GP time". PSP learning modules consist of three half-day
      learning sessions interspersed with 6-8 week action periods. At the end of the
      third learning session, all participants were asked to complete a pen-and-paper
      survey that asked them to rate (a) their satisfaction with the learning module
      components, including the content and (b) the perceived impact the learning has
      had on their practices and patients. METHODS: A total of 887 GPs (response rates
      ranging from 26.0% to 60.2% across three years) and 405 MOAs (response rates from
      21.3% to 49.8%) provided responses on a pen-and-paper survey administered at the
      last learning session of the learning module. The survey asked respondents to
      rate (a) their satisfaction with the learning module components, including the
      content and (b) the perceived impact the learning has had on their practices and
      patients. The psychometric properties (Chronbach's alphas) of the satisfaction
      and impact scales ranged from .82 to .94. RESULTS: Evaluation findings from the
      first three years of the PSP indicated consistently high satisfaction ratings and
      perceived impact on GP practices and patients, regardless of physician
      characteristics (gender, age group) or work-related variables (e.g., time worked
      in family practice). The Advanced Access Learning Module, which offers tools to
      improve office efficiencies, decreased wait times for urgent, regular and third
      next available appointments by an average of 1.2, 3.3, and by 3.4 days across all
      physicians. For the Chronic Disease Management module, over 87% of all GP
      respondents developed a CDM patient registry and reported being able to take
      better care of their patients. After attending the Adult Mental Health module:
      94.1% of GPs agreed that they felt more comfortable helping patients who required
      mental health care; over 82% agreed that their skills and their confidence in
      diagnosing and treating mental health conditions had improved; and 41.0% agreed
      that their frequency of prescribing medications, if appropriate, had decreased.
      Additionally for the Adult Mental Health module, a 3-6 month follow-up survey of
      the GPs indicated that the implemented changes were sustained over time.
      CONCLUSION: GP and medical office assistant participant ratings show that the PSP
      learning modules were consistently successful in providing GPs and their staff
      with new learning that was relevant and could be implemented and used in "real-GP
      time".

PMID- 23140231
TI  - Neurodevelopmental consequences of maternal distress: what do we really know?
AB  - A simple internet search of 'maternal stress and pregnancy' turns up hundreds of
      hits explaining that an adverse intrauterine environment can affect fetal
      development and potentially lead to various learning, behavioral, and mood
      disorders in childhood, as well as complex diseases such as obesity and
      cardiovascular conditions later in life. Indeed, a growing body of literature now
      links several intrauterine challenges, including maternal obesity and stress,
      with adverse developmental outcomes in the child. Over the past 5 years, nearly
      5000 publications have explored the consequences of maternal distress on young
      offspring, a marked increase from the 475 published studies over a comparable
      period 20 years ago. Yet, despite this explosion of research and widespread
      warnings to pregnant mothers, we still lack a basic understanding of the
      pathophysiology linking adverse maternal health to the onset of disease in the
      child, especially regarding how prenatal and perinatal challenges might affect
      brain development. Recent studies have begun to explore the cellular basis of the
      abnormal brain cytoarchitecture associated with fetal exposure to intrauterine
      challenges. Here, our goal is to review the scientific evidence that maternal
      distress interferes with key neurodevelopmental steps, as an entry point toward
      mapping the pathophysiology of pre- and perinatal stress on the unborn child's
      brain.

PMID- 23140232
TI  - Direct detection of acidity, alkalinity, and pH with membrane electrodes.
AB  - An electrochemical sensing protocol based on supported liquid ion-selective
      membranes for the direct detection of total alkalinity of a sample that contains
      a weak base such as Tris (pK(a) = 8.2) is presented here for the first time.
      Alkalinity is determined by imposing a defined flux of hydrogen ions from the
      membrane to the sample with an applied current. The transition time at which the
      base species at the membrane-sample interface depletes owing to diffusion
      limitation is related to sample alkalinity in this chronopotentiometric detection
      mode. The same membrane is shown to detect pH (by zero current potentiometry) and
      acidity and alkalinity (by chronopotentiometry at different current polarity).
      This principle may become a welcome tool for the in situ determination of these
      characteristics in complex samples such as natural waters.

PMID- 23140233
TI  - Towards functional repertoire of the earliest proteins.
AB  - The conserved protein sequence motifs present in all prokaryotic proteomes,
      "omnipresent motifs," presumably, correspond to the earliest proteins of the Last
      Universal Cellular Ancestor, from which all the proteomes have descended. Fifteen
      proteomes, each representing one of the total 15 diverse phyla of 131 Eubacteria
      and Archea, from which the omnipresent elements have been originally derived, are
      exhaustively screened. All those proteins which harbor the omnipresent motifs are
      identified. Six "omnipresent" protein types are revealed which are located in all
      15 proteomes: ABC cassettes, FtsH proteases, translation initiation factors,
      translation elongation factors, isoleucyl-tRNA synthases, and RNA polymerases
      beta'. In addition to the omnipresent motifs, these proteins also contain other
      highly conserved motifs, standing for additional modules of the proteins.
      Remarkably, the identified tentative earliest proteins are responsible for only
      three basic functions: supply of monomers (ABC transporters and proteases),
      protein synthesis (initiation and elongation factors, aminoacyl-tRNA synthases),
      and RNA synthesis (polymerases). No enzymes involved in metabolic activities are
      present in the list of the earliest proteins derived by this approach. Some of
      the omnipresent sequence motifs are found, indeed, in the metabolic enzymes (e.g.
      NTP binding motifs), but these enzymes do not make a sequence matching collection
      of 15 sequences, i.e. they are not omnipresent. Future analysis of less conserved
      sequence motifs may reveal at what degree of conservation (stage of evolution)
      the metabolic enzymes could have entered the scene. 

PMID- 23140234
TI  - Pharmacodynamics of piroxicam from novel solid lipid microparticles formulated
      with homolipids from Bos indicus.
AB  - The dissolution of piroxicam is a limiting step in its bioavailability on account
      of its hydrophobicity. The objective of this research was to formulate novel
      solid lipid microparticles (SLMs) based on homolipids (admixtures of tallow fat
      (TF) and Softisan((r)) 142 (SFT) templated with Phospholipon((r)) 90G (P90G), a
      heterolipid for the delivery of piroxicam. Lipid matrices consisting of TF and
      SFT in ratios of 1:1, 1:2 and 2:1 were templated with the heterolipid, P90G and
      characterized by differential scanning calorimetry (DSC). The SLMs produced by
      hot homogenization technique using the matrices were characterized in terms of
      thermal properties, particle size, morphology, drug encapsulation efficiency,
      stability studies and in vitro diffusion studies. In vivo pharmacodynamic study
      was performed using egg albumin- induced pedal edema in rats. The results showed
      that addition of Softisan((r)) 142 improved the drug holding capacity of the
      micellar solution of 2:1 mixture of TF and SFT. The in vitro diffusion of
      piroxicam from this SLM showed maximum release of 87.53 % and followed non
      Fickian diffusion kinetic mechanism. At dose equivalence of 10 mg,
      piroxicamloaded SLMs showed superior in vivo anti-inflammatory properties at 3 h
      than Feldene((r)) and the pure drug sample. This study has shown that surface
      modified SLMs could confer favourable properties with respect to drug release and
      antiinflammatory activity on SLMs for the delivery of piroxicam, thus encouraging
      further development of the formulations. 

PMID- 23140235
TI  - Structural and magnetic properties of small 4d transition metal clusters: role of
      spin-orbit coupling.
AB  - The spin and orbital magnetic moments, as well as the magnetic anisotropy energy
      (MAE), of small 4d transition metal (TM) clusters are systematically studied by
      using the spin-orbit coupling (SOC) implementation of the density-functional
      theory (DFT). The effects of spin-orbit interactions on geometrical structures
      and spin moments are too weak to alternate relative stabilities of different low
      lying isomers. Remarkable orbital contributions to cluster magnetic moments are
      identified in Ru, Rh, and Pd clusters, in contrast to immediate quenching of the
      atomic orbital moment at the dimer size in other elemental clusters. More
      interestingly, there is always collinearity between total spin and orbital
      moments (antiferromagnetic or ferromagnetic coupling depends on the constituent
      atoms whose 4d subshell is less or more than half-filled). The clusters preserve
      the validity of Hund's rules for the sign of orbital moment. The calculations on
      MAEs reveal the complicated changes of the easy axes in different structures. The
      perturbation theory and the first-principles calculations are compared to
      emphasize how MAEs evolve with cluster size. Finally, large orbital moments
      combined with strong spin-orbit coupling are proposed to account for large MAEs
      in Ru, Rh, and Pd clusters.

PMID- 23140236
TI  - Severe stroke: patient profile and predictors of favorable outcome.
AB  - BACKGROUND: Severe stroke carries high rates of mortality and morbidity. The aims
      of this study were to determine the characteristics of patients who initially
      presented with severe ischemic stroke, and to identify acute and subacute
      predictors of favorable clinical outcome in these patients. METHODS: An
      observational cohort study, Acute Stroke Registry and Analysis of Lausanne
      (ASTRAL), was analyzed, and all patients presenting with severe stroke - defined
      as a National Institute of Health Stroke Scale score of >= 20 on admission - were
      compared with all other patients. In a multivariate analysis, associations with
      demographic, clinical, pathophysiologic, metabolic and neuroimaging factors were
      determined. Furthermore, we analyzed predictors of favorable outcome (modified
      Rankin scale score of <= 3 at 3 months) in the subgroup of severe stroke
      patients. RESULTS:   Of 1915 consecutive patients, 243 (12.7%) presented with
      severe stroke. This was significantly associated with cardio-embolic stroke
      mechanism (odds ratio [OR] 1.74, 95% confidence interval [CI] 1.19-2.54), unknown
      stroke onset (OR 2.35, 95% CI 1.14-4.83), more neuroimaging signs of early
      ischemia (mostly computed tomography; OR 2.65, 95% CI 1.79-3.92), arterial
      occlusions on acute imaging (OR 27.01, 95% CI 11.5-62.9), fewer chronic
      radiologic infarcts (OR 0.43, 95% CI 0.26-0.72), lower hemoglobin concentration
      (OR 0.97, 95% CI 0.96-0.99), and higher white cell count (OR 1.05, 95% CI 1.00
      1.11). In the 68 (28%) patients with favorable outcomes despite presenting with
      severe stroke, this was predicted by lower age (OR 0.94, 95% CI 0.92-0.97),
      preceding cerebrovascular events (OR 3.00, 95% CI 1.01-8.97), hypolipemic
      pretreatment (OR 3.82, 95% CI 1.34-10.90), lower acute temperature (OR 0.43, 95%
      CI 0.23-0.78), lower subacute glucose concentration (OR 0.74, 95% CI 0.56-0.97),
      and spontaneous or treatment-induced recanalization (OR 4.51, 95% CI 1.96-10.41).
      CONCLUSIONS: Severe stroke presentation is predicted by multiple clinical,
      radiologic and metabolic variables, several of which are modifiable. Predictors
      in the 28% of patients with favorable outcome despite presenting with severe
      stroke include hypolipemic pretreatment, lower acute temperature, lower glucose
      levels at 24 h, and arterial recanalization.

PMID- 23140237
TI  - Introduction into PPPM as a new paradigm of public health service: an integrative
      view.
AB  - In the present state of healthcare, usual medical care is generally given to the
      already diseased person, while the key link-personal health monitoring underlain
      by predictive, preventive, and personalised medicine (PPPM) techniques that are
      being intensively elaborated worldwide-is simply missing. It is this link, based
      on the recognition of subclinical conditions, prediction, and further preventive
      measures, that is capable of regulating morbidity and diminishing the rates of
      disability among able-bodied population, thus significantly cutting the
      traditionally high costs of treating the already diseased people. To achieve the
      above-mentioned goal-the elaboration of the PPPM concept and its practical
      implementation-it is necessary to create a fundamentally new strategy based upon
      the subclinical recognition of the signs-bioindicators of cryptic abnormalities
      long before the disease clinically manifests itself. The implementation of PPPM
      programme requires an adjusted technology for the proper interpretation of
      diagnostic data, which would allow for the current 'physician-patient' model to
      be gradually replaced by a novel model, 'medical advisor-healthy men-at-risk'.
      This is the reason for an additional need in organising combinatorial scientific,
      clinical, training and educational projects in the area of PPPM to elicit the
      content of this new branch of medicine.

PMID- 23140238
TI  - Light-driven electron transfer between a photosensitizer and a proton-reducing
      catalyst co-adsorbed to NiO.
AB  - While intermolecular hole-hopping along the surface of semiconductors is known,
      there are no previous examples of electron-hopping between molecules on a
      surface. Herein, we present the first evidence of electron transfer from the
      photoreduced sensitizer Coumarin-343 (C343) to complex 1, both bound on the
      surface of NiO. In solution, 1 has been shown to be a mononuclear Fe-based proton
      reducing catalyst. The reduction of 1 is reversible and occurs within 50 ns after
      excitation of C343. Interfacial recombination between the reduced 1((-)) and NiO
      hole occurs on a 100 MUs time scale by non-exponential kinetics. The observed
      process is the first essential step in the photosensitized generation of H(2)
      from a molecular catalyst in the absence of a sacrificial donor reagent.

PMID- 23140239
TI  - Peripheral adrenoceptors: the impetus behind glucose dysregulation and insulin
      resistance.
AB  - It is now accepted that several pharmacological drug treatments trigger clinical
      manifestations of glucose dysregulation, such as hyperglycaemia, glucose
      intolerance and insulin resistance, in part through poorly understood mechanisms.
      Persistent sympathoadrenal activation is linked to glucose dysregulation and
      insulin resistance, both of which significantly increase the risk of emergent
      endocrinological disorders, including metabolic syndrome and type 2 diabetes
      mellitus. Through the use of targeted mutagenesis and pharmacological methods,
      preclinical and clinical research has confirmed physiological glucoregulatory
      roles for several peripheral alpha- and beta-adrenoceptor subtypes. Adrenoceptor
      isoforms in the pancreas (alpha(2A)  and beta(2) ), skeletal muscle (alpha(1A) 
      and beta(2) ), liver (alpha(1A & B)  and beta(2) ) and adipose tissue (alpha(1A) 
      and beta(1 & 3) ) are convincing aetiological targets that account for both
      immediate and long-lasting alterations in blood glucose homeostasis. Because
      significant overlap exists between the therapeutic applications of numerous
      classes of drugs and their associated adverse side-effects, a better
      understanding of peripheral adrenoceptor-mediated glucose metabolism is thus
      warranted. Therefore, at the same time as providing a brief review of glucose
      homeostasis in the periphery, the present review addresses both functional and
      pathophysiological roles of the mammalian alpha(1) , alpha(2) , and beta
      adrenoceptor isoforms in whole-body glucose turnover. We highlight evidence
      relating to the clinical use of common adrenergic drugs and their impacts on
      glucose metabolism.

PMID- 23140240
TI  - Hepatic and intestinal drug transporters: prediction of pharmacokinetic effects
      caused by drug-drug interactions and genetic polymorphisms.
AB  - Recent studies of membrane transporters have revealed their importance in
      determining the pharmacokinetics of transporter substrates. When drug-drug
      interactions (DDIs) or genetic polymorphisms (i.e., pharmacogenetics) affect the
      activities of transporters, the pharmacokinetics of transporter substrate drugs
      is altered; this alteration influences the substrate drugs' subsequent
      pharmacological or toxicological effects. In predicting these effects
      quantitatively from in vitro experimental results, we must first determine the
      contribution of each transporter to the overall elimination process. Furthermore,
      the accurate estimation of effective inhibitor concentrations at the site of
      interaction (e.g., intestinal lumen, extracellular and intracellular space of
      hepatocytes) is challenging. In predicting pharmacogenetic effects, the
      extrapolation from in vitro observations to in vivo outcomes (e.g., changes in
      intrinsic activities and/or expression levels) is still evolving. In this review,
      we describe the current status of, and difficulties inherent in, the accurate
      prediction of the altered pharmacokinetics caused by transporter-mediated DDIs
      and pharmacogenetics.

PMID- 23140241
TI  - Systems pharmacology to predict drug toxicity: integration across levels of
      biological organization.
AB  - To achieve sensitive and specific mechanism-based prediction of drug toxicity,
      the tools of systems pharmacology will be integrated using structured ontological
      approaches, analytics, mathematics, and statistics. Success of this effort is
      based on the assumption that a systems network that consists of drug-induced
      perturbations of physiological functions can be characterized. This network spans
      the hierarchy of biological organization, from gene to mRNA to protein to
      intracellular organelle to cell to organ to organism. It is populated with data
      from each of these levels of biological organization. These data, from disparate
      sources, include the published literature, drug development archives of all
      approved drugs and drug candidates that did not complete development, and various
      toxicity databases and adverse event reporting systems. The network contains
      interrelated genomics, transcriptomics, and metabolomics data, as well as organ
      and physiological functional data that are derived from the universe of
      information that describes and analyzes drug toxicity. Here we describe advances
      in bioinformatics, computer sciences, next-generation sequencing, and systems
      biology that create the opportunity for integrated systems pharmacology-based
      prediction of drug safety.

PMID- 23140242
TI  - Renal transporters in drug development.
AB  - The kidney plays a vital role in the body's defense against potentially toxic
      xenobiotics and metabolic waste products through elimination pathways. In
      particular, secretory transporters in the proximal tubule are major determinants
      of the disposition of xenobiotics, including many prescription drugs. In the past
      decade, considerable progress has been made in understanding the impact of renal
      transporters on the disposition of many clinically used drugs. In addition, renal
      transporters have been implicated as sites for numerous clinically important drug
      drug interactions. This review begins with a description of renal drug handling
      and presents relevant equations for the calculation of renal clearance, including
      filtration and secretory clearance. In addition, data on the localization,
      expression, substrates, and inhibitors of renal drug transporters are tabulated.
      The recent US Food and Drug Administration drug-drug interaction draft guidance
      as it pertains to the study of renal drug transporters is presented. Renal drug
      elimination in special populations and transporter splicing variants are also
      described.

PMID- 23140244
TI  - Omics and drug response.
AB  - A new generation of technologies commonly named omics permits assessment of the
      entirety of the components of biological systems and produces an explosion of
      data and a major shift in our concepts of disease. These technologies will likely
      shape the future of health care. One aspect of these advances is that the data
      generated document the uniqueness of each human being in regard to disease risk
      and treatment response. These developments have reemphasized the concept of
      personalized medicine. Here we review the impact of omics technologies on one key
      aspect of personalized medicine: the individual drug response. We describe how
      knowledge of different omics may affect treatment decisions, namely drug choice
      and drug dose, and how it can be used to improve clinical outcomes.

PMID- 23140243
TI  - Structure-function of the G protein-coupled receptor superfamily.
AB  - During the past few years, crystallography of G protein-coupled receptors (GPCRs)
      has experienced exponential growth, resulting in the determination of the
      structures of 16 distinct receptors-9 of them in 2012 alone. Including closely
      related subtype homology models, this coverage amounts to approximately 12% of
      the human GPCR superfamily. The adrenergic, rhodopsin, and adenosine receptor
      systems are also described by agonist-bound active-state structures, including a
      structure of the receptor-G protein complex for the beta(2)-adrenergic receptor.
      Biochemical and biophysical techniques, such as nuclear magnetic resonance and
      hydrogen-deuterium exchange coupled with mass spectrometry, are providing
      complementary insights into ligand-dependent dynamic equilibrium between
      different functional states. Additional details revealed by high-resolution
      structures illustrate the receptors as allosteric machines that are controlled
      not only by ligands but also by ions, lipids, cholesterol, and water. This wealth
      of data is helping redefine our knowledge of how GPCRs recognize such a diverse
      array of ligands and how they transmit signals 30 angstroms across the cell
      membrane; it also is shedding light on a structural basis of GPCR allosteric
      modulation and biased signaling.

PMID- 23140245
TI  - Direct-acting antiviral agents for hepatitis C virus infection.
AB  - Two selective inhibitors of the hepatitis C virus (HCV) protease nearly double
      the cure rates for this infection when combined with peginterferon alfa and
      ribavirin. These drugs, boceprevir and telaprevir, received regulatory approval
      in 2011 and are the first direct-acting antiviral agents (DAAs) that selectively
      target HCV. During 2012, at least 30 additional DAAs were in various stages of
      clinical development. HCV protease inhibitors, polymerase inhibitors, and NS5A
      inhibitors (among others) can achieve high cure rates when combined with
      peginterferon alfa and ribavirin and demonstrate promise when used in combination
      with one another. Current research is attempting to improve the pharmacokinetics
      and tolerability of these agents, define the best regimens, and determine
      treatment strategies that produce the best outcomes. Several DAAs will reach the
      market simultaneously, and resources will be needed to guide the use of these
      drugs. We review the clinical pharmacology, trial results, and remaining
      challenges of DAAs for the treatment of HCV.

PMID- 23140246
TI  - Excited-state dynamics of water-soluble polythiophene derivatives: temperature
      and side-chain length effects.
AB  - We report synthesis and detailed spectroscopic study of three water-soluble
      polythiophene derivatives with distinct homologous oligo(ethylene oxide) side
      chain lengths and lower critical solution temperatures (LCSTs). The linear
      absorption spectra exhibit reversible shifts and broadening with the variation of
      their aqueous solution temperature, whereas the corresponding steady-state
      fluorescence emission spectra were found to show negligible shifts and only minor
      changes in their line shape. Measurements of picosecond time-resolved
      fluorescence at chosen emission wavelengths reveal a strong dependence of the
      isotropic decays on both side-chain length and aqueous solution temperature. With
      lengthening of the side chain, the isotropic decays become not only remarkably
      slow but also increasingly complex. Except for the polymer with the shortest side
      chain, significant acceleration of the isotropic decays was found when the
      solution temperature was raised to the corresponding LCSTs and beyond, which
      further causes formation of large aggregates as evident by the physical
      appearance change from clear solutions to turbid suspensions. Direct evidence for
      a temperature-induced change of polymer chain conformation was obtained through
      measurements of time-resolved fluorescence anisotropies, which are characterized
      by a substantial increase of the initial values from ~0.2 to 0.4 and the
      appearance of a pronounced fast decay component with an estimated lifetime of 36
      ps. The high initial anisotropy of ~0.4 observed for the two polymers with longer
      side-chains above their LCSTs suggests that the polymer chains are highly ordered
      in the aggregates. The observed effects of side-chain length and solution
      temperature are discussed by considering the conformational relaxation of the
      polymer backbones and occurrence of interchain energy transfer.

PMID- 23140247
TI  - Serological and molecular investigation into the role of wild birds in the
      epidemiology of West Nile virus in Greece.
AB  - BACKGROUND: A West Nile virus (WNV) disease outbreak occurred in 2010 in northern
      Greece with a total of 262 laboratory-confirmed human cases and 35 deaths. A
      serological and molecular surveillance was conducted on samples of hunter
      harvested wild birds prior to and during the outbreak. FINDINGS: Serum and tissue
      samples from 295 resident and migratory wild birds, hunter-harvested during the
      2009-2010 and 2010-2011 hunting seasons at the epicenter of the outbreak in
      northern Greece, were tested for the presence of WNV-specific antibodies by
      immunofluorescence assay and virus neutralization test. WNV neutralizing
      antibodies were detected in 53 avian samples. Fourteen positive sera were
      obtained from birds hunter-harvested up to 8 months prior to the human outbreak.
      Specific genetic determinants of virulence (His249Pro NS3 mutation, E
      glycosylation motif) were recognized in a WNV lineage 2 strain isolated from a
      hunter-harvested Eurasian magpie and a nucleotide mismatch was revealed between
      this strain and a mosquito WNV strain isolated one month earlier in the same
      area. CONCLUSIONS: This is the first report regarding exposure of wild birds to
      WNV prior to the 2010 outbreak, in Greece. Results provide evidence of the
      implication of wild birds in a local enzootic cycle that could allow maintenance
      and amplification of the virus before and during the outbreak. Findings of past
      exposure of migratory birds to WNV upon their arrival in Greece during autumn
      migration, suggest avian species with similar migration traits as candidates for
      the introduction of WNV into Greece. The possibility that an endemic circulation
      of WNV could have caused the outbreak, after an amplification cycle due to
      favorable conditions cannot be excluded.

PMID- 23140248
TI  - Characteristics of Staphylococcus aureus small colony variant and its parent
      strain isolated from chronic mastitis at a dairy farm in Beijing, China.
AB  - Staphylococcus aureus is a major pathogen associated to bovine mastitis and has
      the ability to form a slow-growing population termed the small colony variants
      (SCVs). From 20 samples of 5 chronic S. aureus cases, 1 SCV isolate (SCV102) was
      recovered simultaneously with 1 of 8 S. aureus isolates. SCV102 showed auxotrophy
      for thymidine and had a slow growth rate. Intracellular persistence in human
      mammary epithelial cells (HBL100cell line) monolayer revealed that SCV102 isolate
      had minimal cytopathological effects compared with its parent strains. SCV102
      isolate and its parent strain S. aureus 101 indicate similar resistant pattern to
      four antibiotics. On the contrary, the minimal inhibitory concentrations values
      for chloramphenicol and sulfadimethoxine were much higher in SCV102 than that of
      S. aureus 101. To the best of our knowledge this is the first time the isolation
      of S. aureus SCV102 from a persistent bovine mastitis has been reported in
      Beijing (China). This study suggests that SCV102 isolate may be an important
      contributor to persistent bovine mastitis.

PMID- 23140249
TI  - A pilot randomised control trial of the effectiveness of a biofeedback mouse in
      reducing self-reported pain among office workers.
AB  - A pilot study examined the effectiveness of a biofeedback mouse in reducing upper
      extremity pain and discomfort in office workers; in addition, relative mouse use
      (RMU), satisfaction and the feasibility of running a randomised controlled trial
      (RCT) in a workplace setting were evaluated. The mouse would gently vibrate if
      the hand was idle for more than 12 s. The feedback reminded users to rest the arm
      in neutral, supported postures. Analysis showed a statistically significant
      reduction in shoulder pain and discomfort for the intervention group at T2 (38.7%
      lower than controls). Statistically significant differences in RMU time between
      groups were seen post intervention (-7% at T1 and +15% at T2 for the intervention
      group). Fifty-five percent of the intervention group was willing to continue
      using the mouse. It appears feasible to perform an RCT for this type of
      intervention in a workplace setting. Further study including more participants is
      suggested. PRACTITIONER SUMMARY: The study findings support the feasibility of
      conducting randomised control trials in office settings to evaluate ergonomics
      interventions. The intervention resulted in reduced pain and discomfort in the
      shoulder. The intervention could be a relevant tool in the reduction of upper
      extremity musculoskeletal disorder. Further research will better explain the
      study's preliminary findings.

PMID- 23140250
TI  - An innovative OSCE clinical log station: a quantitative study of its influence on
      Log use by medical students.
AB  - BACKGROUND: A Clinical Log was introduced as part of a medical student learning
      portfolio, aiming to develop a habit of critical reflection while learning was
      taking place, and provide feedback to students and the institution on learning
      progress. It was designed as a longitudinal self-directed structured record of
      student learning events, with reflection on these for personal and professional
      development, and actions planned or taken for learning.As incentive was needed to
      encourage student engagement, an innovative Clinical Log station was introduced
      in the OSCE, an assessment format with established acceptance at the School. This
      study questions: How does an OSCE Clinical Log station influence Log use by
      students? METHODS: The Log station was introduced into the formative, and
      subsequent summative, OSCEs with careful attention to student and assessor
      training, marking rubrics and the standard setting procedure. The scoring process
      sought evidence of educational use of the log, and an ability to present and
      reflect on key learning issues in a concise and coherent manner. RESULTS:
      Analysis of the first cohort's Log use over the four-year course (quantified as
      number of patient visits entered by all students) revealed limited initial use.
      Usage was stimulated after introduction of the Log station early in third year,
      with some improvement during the subsequent year-long integrated community-based
      clerkship. Student reflection, quantified by the mean number of characters in the
      'reflection' fields per entry, peaked just prior to the final OSCE (mid-Year 4).
      Following this, very few students continued to enter and reflect on clinical
      experience using the Log. CONCLUSION: While the current study suggested that we
      can't assume students will self-reflect unless such an activity is included in an
      assessment, ongoing work has focused on building learner and faculty confidence
      in the value of self-reflection as part of being a competent physician.

PMID- 23140251
TI  - Combined effects of interfacial permittivity variations and finite ionic sizes on
      streaming potentials in nanochannels.
AB  - In this work, we investigate the effects of local permittivity variations,
      induced by a preferential orientation and exclusion of water dipoles close to
      channel walls, and the effects of finite-sized ions on the induced streaming
      potential in nanochannels. We make a detailed analysis of the underlying
      physicochemical interactions by considering combinations of cases where ions are
      considered to be point sized/finite sized and permittivity variation effects to
      be present/absent. By accounting for the dielectric friction (which in turn is a
      function of the local permittivity) in addition to the classical Stokes friction,
      we show that for high interfacial potentials and narrow confinements, the induced
      streaming potential field for the cases in which the polarization effects are
      considered for finite-sized ions is remarkably higher than for the cases in which
      the polarization effects are neglected. Thus, by coupling the nonlinear effects
      of finite-sized ions and water dipole polarization along with the dielectric
      friction, we open a new paradigm of streaming potential predictions for narrow
      fluidic confinements, bearing far-ranging scientific and technological
      consequences in nanoscale science and technology.

PMID- 23140252
TI  - Three-dimensional human gait pattern - reference data for normal men.
AB  - The aim of this research was to establish a kinematic pattern of adult gait for
      motion analysis system BTS Smart-E used in the research conducted in the
      Laboratory of Biomechanical Analysis, University School of Physical Education,
      Wroclaw. This research presents the results of gait patterns for a group of 17
      adult males for three speed levels: high (1), preferred (2), and low (3).
      Subject's sex, age and speed of gait are to be considered in the kinematic normal
      gait pattern. No statistically significant differences were observed between the
      right and the left limb. However, differences between the high, preferred and low
      gait speed were noticeable. An increase in gait speed was related to the change
      in the angular range of motion in the hip, knee and ankle joints sagittal plane.
      The range of motion in joints mostly increased with the subjects' speed. No
      significant differences between the range of motion and speed were observed in
      the ankle joint.

PMID- 23140253
TI  - Incomplete nonsense-mediated decay facilitates detection of a multi-exonic
      deletion mutation in SGCE.
AB  - Mutations in SGCE represent the major cause of the myoclonus-dystonia syndrome
      (DYT11), an autosomal dominant disorder of reduced penetrance. Virtually all
      affected individuals have myoclonus, which is concentrated in the upper
      extremities, neck and trunk. Over half of patients have dystonia, usually
      affecting the neck or arms. SGCE is maternally imprinted. Of the more than 70
      SGCE mutations reported in the literature, 18 are large deletions disrupting at
      least one exon. Therefore, testing for exonic deletions should be considered in
      individuals with a classic phenotype in whom Sanger sequencing is unrevealing.
      However, standard methodologies for detection of exonic deletion mutations are
      expensive, labor intensive and can produce false negatives. Herein, we report the
      use of cDNA derived from leukocyte RNA to identify a deletion mutation (exons 4
      and 5) of SGCE in a family with DYT11. Residual RNA from incomplete nonsense
      mediated decay permitted reverse transcription to cDNA. Breakpoints of the 8939
      bp heterozygous deletion were then defined with long-range polymerase chain
      reaction and Sanger sequencing. Use of cDNA generated by reverse transcription of
      leukocyte RNA can reduce the costs associated with diagnostic genetic testing and
      can facilitate detection of deletion mutations. 

PMID- 23140255
TI  - A review of cost-effectiveness of palivizumab for respiratory syncytial virus.
AB  - Palivizumab prophylaxis has been demonstrated to reduce the number of
      hospitalizations attributable to respiratory syncytial virus in high-risk
      infants. However, as palivizumab acquisition costs are high, quantifying cost
      effectiveness is important. The primary aim of this review was to examine the
      cost-effectiveness of palivizumab across numerous indications in high-risk
      infants and to report on factors that may impact outcomes. A systematic
      literature search was conducted to identify pharmacoeconomic analyzes of
      palivizumab compared to no prophylaxis for respiratory syncytial virus in infants
      and young children. A total of 28 articles met inclusion criteria and were
      subsequently assigned quality scores according to the Quality of Health Economic
      Studies criteria. Results varied according to perspective, input parameters,
      outcome measures, populations and base-case and sensitivity analyses. Overall,
      cost-effectiveness results were inconsistent. Some studies reported favorable
      outcomes, while others did not, or were inconclusive. Factors to consider in the
      interpretation of such economic evaluations are discussed.

PMID- 23140254
TI  - Impact of gender on response to highly active antiretroviral therapy in HIV-1
      infected patients: a nationwide population-based cohort study.
AB  - BACKGROUND: Impact of gender on time to initiation, response to and risk of
      modification of highly active antiretroviral therapy (HAART) in HIV-1 infected
      individuals is still controversial. METHODS: From a nationwide cohort of Danish
      HIV infected individuals we identified all heterosexually infected women (N=587)
      and heterosexually infected men (N=583) with no record of Hepatitis C infection
      diagnosed with HIV after 1 January 1997. Among these subjects, 473 women (81%)
      and 435 men (75%) initiated HAART from 1 January 1997 to 31 December 2009. We
      used Cox regression to calculate hazard ratio (HR) for time to initiation of
      HAART, Poisson regression to assess incidence rate ratios (IRR) of risk of
      treatment modification the first year, logistic regression to estimate
      differences in the proportion with an undetectable viral load, and linear
      regression to detect differences in CD4 count at year 1, 3 and 6 after start of
      HAART. RESULTS: At initiation of HAART, women were younger, predominantly of
      Black ethnicity and had a higher CD4 count (adjusted p=0.026) and lower viral
      load (adjusted p=0.0003). When repeating the analysis excluding pregnant women no
      difference was seen in CD4 counts (adjusted p=0.21). We observed no delay in time
      to initiation of HAART in women compared to men (HR 0.91, 95% CI 0.79-1.06).
      There were no gender differences in risk of treatment modification of the
      original HAART regimen during the first year of therapy for either toxicity (IRR
      0.97 95% CI 0.66-1.44) or other/unknown reasons (IRR 1.18 95% CI 0.76-1.82).
      Finally, CD4 counts and the risk of having a detectable viral load at 1, 3 and 6
      years did not differ between genders. CONCLUSIONS: In a setting with free access
      to healthcare and HAART, gender does neither affect time from eligibility to
      HAART, modification of therapy nor virological and immunological response to
      HAART. Differences observed between genders are mainly attributable to initiation
      of HAART in pregnant women.

PMID- 23140256
TI  - A novel and efficient ligand-based virtual screening approach using the HWZ
      scoring function and an enhanced shape-density model.
AB  - In this work, we extend our previous ligand shape-based virtual screening
      approach by using the scoring function Hamza-Wei-Zhan (HWZ) score and an enhanced
      molecular shape-density model for the ligands. The performance of the method has
      been tested against the 40 targets in the Database of Useful Decoys and compared
      with the performance of our previous HWZ score method. The virtual screening
      results using the novel ligand shape-based approach demonstrated a favorable
      improvement (area under the receiver operator characteristics curve AUC = .89 +/-
      .02) and effectiveness (hit rate HR(1%) = 53.0% +/- 6.3 and HR(10%) = 71.1% +/-
      4.9). The comparison of the overall performance of our ligand shape-based method
      with the highest ligand shape-based virtual screening approach using the data
      fusion of multi queries showed that our strategy takes into account deeper the
      chemical information of the set of active ligands. Furthermore, the results
      indicated that our method are suitable for virtual screening and yields superior
      prediction accuracy than the other study derived from the data fusion using five
      queries. Therefore, our novel ligand shape-based screening method constitutes a
      robust and efficient approach to the 3D similarity screening of small compounds
      and open the door to a whole new approach to drug design by implementing the
      method in the structure-based virtual screening. 

PMID- 23140257
TI  - Sex hormone-binding globulin as a marker for the thrombotic risk of hormonal
      contraceptives: a rebuttal.

PMID- 23140258
TI  - Update on drug interactions with phosphodiesterase-5 inhibitors prescribed as
      first-line therapy for patients with erectile dysfunction or pulmonary
      hypertension.
AB  - Phosphodiesterase-5 inhibitors (PDE5i, sildenafil, vardenafil, tadalafil and
      avanafil) are a first-line medical therapy for erectile dysfunction (ED). In all
      likelihood, PDE5i usage will increase because sildenafil (Viagra(r) and
      Revatio(r)) and tadalafil (Cialis(r) and Adcirca(r)) have recently been
      recommended as first-line therapy for patients with pulmonary hypertension (PH).
      PDE5i exhibit higher plasma concentrations when co-administered with cytochrome P
      (CYP) 3A inhibitors, which influences their side-effect profile. The higher PDE5i
      plasma concentrations, caused by CYP3A inhibitors, influence the severity and
      timing of PDE5i drug interactions and require dose adjustment. PDE5i are safe
      when used with most antihypertensive agents, but co-administration with nitrates
      or alpha-blockers can cause severe hypotension and syncope. Dose adjustment is
      also necessary when PDE5i are co-administered with CYP3A inducers. The
      combination of oral tadalafil and bosentan (endothelin receptor antagonist)
      reduces tadalafil levels and requires dose adjustment. Current literature reports
      a number of interactions between PDE5i and other agents and further studies are
      needed to expand our knowledge base of these interactions. This review discusses
      relevant PDE5i drug interactions, including those with CYP 450 inhibitors and
      inducers which are frequently used during the treatment of ED and PH.

PMID- 23140259
TI  - Intact skin and not stripped skin is crucial for the safety and efficacy of
      peanut epicutaneous immunotherapy (EPIT) in mice.
AB  - BACKGROUND: Epicutaneous immunotherapy (EPIT) on intact skin with an
      epicutaneous delivery system has already been used in preclinical and clinical
      studies. In epicutaneous vaccination and immunotherapy, the stripping of skin
      before application of the allergen is suggested to facilitate the passage of
      allergen through immune cells. OBJECTIVES: The aim of this study was to compare
      the immunological response induced by EPIT performed on intact and stripped skin
      in a mouse model of peanut allergy. METHODS: After oral sensitization with peanut
      and cholera toxin, BALB/c mice were epicutaneously treated using an epicutaneous
      delivery system (Viaskin(r) (DBV Technologies, Paris) applied either on intact
      skin or on stripped skin. Following EPIT, mice received an exclusive oral peanut
      regimen, aimed at triggering esophageal and jejunal lesions. We assessed
      eosinophil infiltration by histology, mRNA expression in the esophagus, antibody
      levels and peripheral T-cell response. RESULTS: EPIT on intact skin significantly
      reduced Th2 immunological response (IgE response and splenocyte secretion of Th2
      cytokines) as well as esophageal eosinophilia (2.7 +/- 0.9, compared to Sham 19.9
      +/- 1.5, p < 0.01), mRNA expression of Th2 cytokines in tissue and intestinal
      villus sub-atrophia (2.9 +/- 0.2 vs Sham, 2.1 +/- 0.2, p < 0.05). By contrast,
      EPIT on stripped skin reinforced Th2 systemic immunological response as well as
      eosinophil infiltration (26.8 +/- 15.1), mRNA expression of Th2 cytokines and
      duodenal villus/crypt-ratio (2.4 +/- 0.3). CONCLUSIONS: Epicutaneous allergen
      specific immunotherapy needs the integrity of superficial layers of the stratum
      corneum to warranty safety of treatment and to induce a tolerogenic profile of
      the immune response.

PMID- 23140260
TI  - An overview of preparation and evaluation sustained-release injectable
      microspheres.
AB  - Recently, sustained-release injectable microspheres as a novel parenteral
      administration system have been interested on for many years, due to the
      excellent advantages when compared to traditional dosage forms: less
      administration frequency, lower adverse side effects and no need for a surgical
      procedure. Therefore, major progresses in the development of another successful
      marketed sustained-release injectable formation have been made, but most
      investigations are merely limited in laboratory levels; in addition, few reports
      focus on giving some positive guidance to launch these novel microspheres into
      market. This review addressed some commonly used polymers, preparation methods
      and sterilization processes relating to biodegradable microspheres. Moreover, the
      processes for measuring the sustained-release behaviour of this novel system are
      summarized in this report, including the methods to determine the in vitro and in
      vivo release behaviours and the strategies to analyse the in vitro and in vivo
      correlations.

PMID- 23140261
TI  - Metformin reduces vascular endothelial dysfunction caused by an acute glucose
      load in patients with hypertension.
AB  - BACKGROUND: To investigate the effects of a single dose of metformin (MF) on
      endothelium-dependent vasodilatation and serum antioxidant and free fatty acid
      levels in patients with primary hypertension (PH) after an acute glucose load.
      MATERIALS AND METHODS: Patients with untreated PH were randomized to a no
      metformin group (PH, n = 34) and a metformin group (PH+ MF, n = 28) who received
      a single dose of 500 mg metformin before testing. Healthy volunteers (n = 31)
      served as a control group. Brachial artery endothelium-dependent flow-mediated
      vasodilatation (FMD) was determined at 0, 1, 2 and 3 h after glucose load. Levels
      of serum superoxide dismutase (SOD), total antioxidant capacity (T-AOC), anti
      superoxide anion free radical (AntiO2) and free fatty acids (FFA) were measured.
      RESULTS: The FMD in the PH group decreased significantly 1 h after glucose load
      (PH: 10.9 +/- 2.9% vs 13.67 +/- 3.42% before glucose load). Metformin inhibited
      the effects of glucose load on FMD. At 1 h after acute glucose load, the
      concentrations of SOD, T-AOC and AntiO2 in the PH group decreased significantly
      compared with their fasting levels, and metformin inhibited the acute glucose
      load-induced decline in SOD and T-AOC levels. CONCLUSIONS: Metformin can prevent
      transient endothelial dysfunction caused by acute glucose load in patients with
      PH.

PMID- 23140262
TI  - Influence of time of rest on the power decrease during exercising on the inclined
      plane.
AB  - The aim of this paper is to investigate the influence of the time of rest on the
      change of maximal and average power as a function of time during training on an
      inclined plane. The values of power, developed during 7 series of 10 bounces with
      a 0.5 and 1 minute break, were analyzed. The research was conducted on 10 female
      students from the second year of master studies with a major of physical
      education. Taking into account the results obtained, which were compared to data
      from other sources, it is possible to conclude that the value of maximal power
      for the whole group examined during the training with a 0.5 minute break
      decreased by 22%, and for the training with a 1 minute break by 12%. One can
      assume that the training with a 0.5 minute break was more tiring, and for that
      reason students were not able to regenerate fully so as to bounce in the
      subsequent series. That is why one should say that the second method of training
      is more efficient for the evaluation of the maximal power of the contestant.

PMID- 23140263
TI  - Revealing the hot bands in the regions of the N-H and C-H stretch fundamentals of
      pyrrole.
AB  - Photoacoustic Raman spectra of gaseous pyrrole in the 3504-3535 and 3068-3152 cm(
      1) energetic windows were measured, to obtain new information about the hot bands
      in the vicinity of the N-H(nu1) and C-H(nu2) stretch fundamentals, respectively.
      The observed vibrational patterns are characterized by sharp Q-branches, where
      the strong bands reflect the fundamentals and the weaker ones, as established
      from their temperature dependence, are hot bands. From the simulation of the
      observed spectra, the band origins and nondiagonal anharmonicities were
      determined. Comparison of the latter values to the anharmonicities, x(ij) (i = 1,
      2 and j = 16, 15, 14, 12, 11) obtained from anharmonic calculations at the
      B3LYP/6-311++G(d,p), B3LYP/cc-pVQZ and MP2/cc-pVTZ levels, aided the tentative
      assignment of the hot bands. The retrieved parameters add new data to the
      extensive set of already known vibrational constants of pyrrole.

PMID- 23140264
TI  - Association of age at menarche with metabolic syndrome and its components in
      rural Bangladeshi women.
AB  - BACKGROUND: Early age at menarche is associated with increased risk of metabolic
      syndrome in both China and the West. However, little is known about the impact of
      age at menarche and metabolic syndrome in South Asian women, including those from
      low-income country, where age at menarche is also falling. The aim of the present
      study was to investigate whether age at menarche is inversely associated with
      metabolic syndrome in Bangladeshi women, who are mostly poor and have limited
      access to and or poor health care facilities. METHODS: This community-based cross
      sectional study was performed using 1423 women aged between 15-75 years from
      rural Bangladesh in 2009 and 2010. Metabolic syndrome was defined according to
      standard NCEP-ATP III criteria. Logistic regression was used to estimate the
      association between age at menarche and metabolic syndrome, with adjustment of
      potential confounding variables, including age, education, marital status,
      tobacco users, use of contraceptives and number of pregnancies. RESULTS: Early
      onset of menarche (<12 years) as compared to late onset (>13 years) was found to
      be associated with a higher prevalence of metabolic syndrome (odds ratio=1.55; 95
      % confidence interval =1.05-2.30). Age at onset of menarche was also inversely
      associated with prevalence of high triglycerides (P for trend <0.01) and low high
      density lipoprotein cholesterol (P for trend = 0.01), but positively associated
      with prevalence of high fasting blood glucose (P for trend =0.02). However, no
      significant association was found between age at menarche, high blood pressure
      and elevated waist circumference. CONCLUSION: Early onset of menarche might
      promote or trigger development of metabolic syndrome. Thus, knowledge of the
      history of age at onset of menarche may be critical in identifying women at risk
      of developing metabolic syndrome and those likely to benefit the most from early
      interventions.

PMID- 23140266
TI  - Regenerative medicine, stem cells, and low-level laser therapy: future
      directives.

PMID- 23140265
TI  - Laser heating of gold nanospheres functionalized with octreotide: in vitro effect
      on HeLa cell viability.
AB  - OBJECTIVE: The aim of this study was to assess the effect of laser heating a well
      characterized gold nanoparticle (AuNP)-octreotide system on HeLa cell viability,
      to evaluate its potential as a suitable agent for plasmonic photothermal therapy.
      BACKGROUND DATA: Octreotide is a synthetic peptide derivative of somatostatin
      with an effect on the survival of HeLa cells. Peptides bound to AuNPs are
      biocompatible and stable multimeric systems with target-specific molecular
      recognition. METHODS: Octreotide was conjugated to AuNPs (~20 nm) by spontaneous
      reaction with the thiol groups. The nanoconjugate was characterized by
      transmission electron microscopy (TEM), Fourier transform infrared spectroscopy
      (FT-IR), ultraviolet visible spectroscopy (UV-Vis), X-ray photoelectron
      spectroscopy (XPS), and Raman spectroscopy. Irradiation experiments were
      conducted using an Nd:YAG laser pulsed for 5 ns at 532 nm with a repetition rate
      of 10 Hz for up to 6 min while delivering an average irradiance of 0.65 W/cm(2).
      HeLa cells were incubated at 37 degrees C (1) with AuNP-citrate, (2) with AuNP
      octreotide, or (3) without nanoparticles. RESULTS: After laser irradiation, the
      presence of AuNP caused a significant increase in the temperature of the medium
      (48 degrees C vs. 38.3 degrees C of that without AuNP). The AuNP-octreotide
      system resulted in a significant decrease in cell viability of up to 6 % compared
      with the AuNP-citrate system (15.8+/-2.1%). Two possible mechanisms could be at
      play: (1) octreotide alone exerts an effect on survival HeLa cells, or (2) the
      release of heat (~727 degrees C per nanoparticle) in the membranes or cytoplasm
      of the cells caused by the interaction between AuNP-octreotide and somatostatin
      receptors reduced viability. CONCLUSIONS: The AuNP-octreotide system exhibited
      properties suitable for plasmonic photothermal therapy in the treatment of
      cervical cancer.

PMID- 23140267
TI  - Stability of platinum nanoparticles supported on SiO2/Si(111): a high-pressure X
      ray photoelectron spectroscopy study.
AB  - The stability of Pt nanoparticles (NPs) supported on ultrathin SiO(2) films on
      Si(111) was investigated in situ under H(2) and O(2) (0.5 Torr) by high-pressure
      X-ray photoelectron spectroscopy (HP-XPS) and ex situ by atomic force microscopy
      (AFM). No indication of sintering was observed up to 600  degrees C in both
      reducing and oxidizing environments for size-selected Pt NPs synthesized by
      inverse micelle encapsulation. However, HP-XPS revealed a competing effect of
      volatile PtO(x) desorption from the Pt NPs (~2 and ~4 nm NP sizes) at
      temperatures above 450  degrees C in the presence of 0.5 Torr of O(2). Under
      oxidizing conditions, the entire NPs were oxidized, although with no indication
      of a PtO(2) phase, with XPS binding energies better matching PtO. The stability
      of catalytic NPs in hydrogenation and oxidation reactions is of great importance
      due to the strong structure sensitivity observed in a number of catalytic
      processes of industrial relevance. An optimum must be found between the
      maximization of the surface active sites and metal loading (i.e., minimization of
      the NP size), combined with the maximization of their stability, which, as it
      will be shown here, is strongly dependent on the reaction environment.

PMID- 23140268
TI  - Understanding growth kinetics of nanorods in microemulsion: a combined
      fluorescence correlation spectroscopy, dynamic light scattering, and electron
      microscopy study.
AB  - Even though nanostructures of various shapes and sizes can be controlled by
      microemulsions, there is substantial difficulty in understanding their growth
      mechanism. The evolution of nanostructures from the time of mixing of reactants
      to their final stage is a heterogeneous process involving a variety of
      intermediates. To obtain a deeper insight into these kinetic steps, we studied
      the slow growth kinetics (extending over eight days) of iron oxalate nanorods
      inside the polar core of water-in-oil microemulsion droplets made of
      cetyltrimethylammonium bromide/1-butanol/isooctane. Fluorescence correlation
      spectroscopy (FCS), dynamic light scattering (DLS), and transmission electron
      microscopy (TEM) have been employed to monitor the nanostructure growth at (near)
      the single-droplet level and in an ensemble. Analyzing FCS data with suitable
      kinetic model we obtain transient dimer lifetime (28 MUs) and the droplet fusion
      rates (and fusion tendency) on each day as the reaction proceeds. The droplet
      fusion rate is found to directly control the nanorod growth in microemulsion
      solution and attains its maximum value (3.55 * 10(4) s(-1)) on day 6, when long
      nanorods are found in TEM data, implying that more and more reactants are fed
      into the growing system at this stage. Combining FCS, DLS, and TEM results, we
      find three distinct periods in the entire growth process: a long nucleation
      dominant nanoparticle growth period which forms nanoparticles of critical
      (average) size of ~53 nm, followed by a short period where isotropic
      nanoparticles switch to anisotropic growth to form nanorods, and finally
      elongation of nanorods and growth (and shrinking) of nanoparticles.

PMID- 23140269
TI  - The inflammatory biomarker YKL-40 at admission is a strong predictor of overall
      mortality.
AB  - OBJECTIVES: YKL-40 is an inflammatory biomarker associated with disease activity
      and mortality in patients with diseases characterized by inflammation and tissue
      remodelling. The aim of this study was to describe the prognostic value of YKL-40
      in an unselected patient population. DESIGN: In consecutive patients admitted to
      hospital during a 1-year period, blood was collected and information regarding
      final diagnosis and mortality was collected. Median follow-up time was 11.5
      years. SETTING: District hospital, Copenhagen, Denmark. PATIENTS: A total of 1407
      patients >40 years of age were admitted acutely. MAIN OUTCOME MEASURE: All-cause
      mortality. RESULTS: Median YKL-40 was increased in patients (157 MUg L(-1) ,
      range 13-7704 MUg L(-1) ) compared to healthy controls (40 MUg L(-1) , range 29
      58 MUg L(-1) ; P < 0.001). Patients with YKL-40 in the highest quartile had a
      hazard ratio (HR) of 7.1 [95% confidence interval (CI) 4.2-12.0] for all-cause
      mortality in the first year and 3.4 (95% CI 2.8-4.2) in the total study period,
      compared to those in the lowest quartile (HR = 1). The HR for death for all
      patients with YKL-40 above the normal age-corrected 95th percentile was 2.1 (95%
      CI 1.6-2.7) after 1 year and 1.5 (95% CI 1.3-1.7) during the total study period,
      compared to patients with YKL-40 below the age-corrected 95th percentile. The
      results of multivariable analysis showed that YKL-40 was an independent biomarker
      of mortality; this was most significant in the first year. YKL-40 was a marker of
      prognosis in all disease categories. The HR for death was increased in patients
      with YKL-40 above the normal age-corrected 95th percentile in healthy subjects
      independent of type of disease (all P < 0.001). CONCLUSION: The level of YKL-40
      at admission is a strong predictor of overall mortality, independent of diagnosis
      and could be useful as a biomarker in the acute evaluation of all patients.

PMID- 23140270
TI  - The Computer-based Health Evaluation Software (CHES): a software for electronic
      patient-reported outcome monitoring.
AB  - BACKGROUND: Patient-reported Outcomes (PROs) capturing e.g., quality of life,
      fatigue, depression, medication side-effects or disease symptoms, have become
      important outcome parameters in medical research and daily clinical practice.
      Electronic PRO data capture (ePRO) with software packages to administer
      questionnaires, storing data, and presenting results has facilitated PRO
      assessment in hospital settings. Compared to conventional paper-pencil versions
      of PRO instruments, ePRO is more economical with regard to staff resources and
      time, and allows immediate presentation of results to the medical staff.The
      objective of our project was to develop software (CHES - Computer-based Health
      Evaluation System) for ePRO in hospital settings and at home with a special focus
      on the presentation of individual patient's results. METHODS: Following the
      Extreme Programming development approach architecture was not fixed up-front, but
      was done in close, continuous collaboration with software end users (medical
      staff, researchers and patients) to meet their specific demands. Developed
      features include sophisticated, longitudinal charts linking patients' PRO data to
      clinical characteristics and to PRO scores from reference populations, a web
      interface for questionnaire administration, and a tool for convenient creating
      and editing of questionnaires. RESULTS: By 2012 CHES has been implemented at
      various institutions in Austria, Germany, Switzerland, and the UK and about 5000
      patients participated in ePRO (with around 15000 assessments in total). Data
      entry is done by the patients themselves via tablet PCs with a study nurse or an
      intern approaching patients and supervising questionnaire completion. DISCUSSION:
      During the last decade several software packages for ePRO have emerged for
      different purposes. Whereas commercial products are available primarily for ePRO
      in clinical trials, academic projects have focused on data collection and
      presentation in daily clinical practice and on extending cancer registries with
      PRO data. CHES includes several features facilitating the use of PRO data for
      individualized medical decision making. With its web-interface it allows ePRO
      also when patients are home. Thus, it provides complete monitoring of
      patients'physical and psychosocial symptom burden.

PMID- 23140271
TI  - Intermolecular interactions between the neurotensin and the third extracellular
      loop of human neurotensin 1 receptor.
AB  - Neurotensin (NT) is a tridecapeptide hormone in the periphery and
      neurotransmitter in the brain that principally activates three receptor subtypes,
      named NTS1, NTS2, and NTS3. Since little is known about its structure in the
      presence of its principal receptor NTS1, we determined it using the key domain of
      the receptor, i.e. the third extracellular loop. We conclude the following: (i)
      for the receptor fragment, NT binding modifies its central part, underlying the
      great flexibility and adaptability of this region; (ii) for bound NT, the
      extended conformation of its C-terminus is confirmed for the first time in
      experimental conditions and in the presence of a part of the receptor; and (iii)
      despite some substitutions, the human receptor residues that are involved in the
      interaction with NT could be similar to those of the rat receptor which play an
      important role in NT binding. 

PMID- 23140272
TI  - Frank-ter Haar syndrome associated with sagittal craniosynostosis and raised
      intracranial pressure.
AB  - BACKGROUND: Frank-ter Haar syndrome is a rare disorder associated with skeletal,
      cardiac, ocular and craniofacial features including hypertelorism and
      brachycephaly. The most common underlying genetic defect in Frank-ter Haar
      syndrome appears to be a mutation in the SH3PXD2B gene on chromosome 5q35.1.
      Craniosynostosis, or premature fusion of the calvarial sutures, has not
      previously been described in Frank-ter Haar syndrome. CASE PRESENTATION: We
      present a family of three affected siblings born to consanguineous parents with
      clinical features in keeping with a diagnosis of Frank-ter Haar syndrome. All
      three siblings have a novel mutation caused by the deletion of exon 13 of the
      SH3PXD2B gene. Two of the three siblings also have non-scaphocephalic sagittal
      synostosis associated with raised intracranial pressure. CONCLUSION: The clinical
      features of craniosynostosis and raised intracranial pressure in this family with
      a confirmed diagnosis of Frank-ter Haar syndrome expand the clinical spectrum of
      the disease. The abnormal cranial proportions in a mouse model of the disease
      suggests that the association is not coincidental. The possibility of
      craniosynostosis should be considered in individuals with a suspected diagnosis
      of Frank-ter Haar syndrome.

PMID- 23140273
TI  - Attention deficit hyperactivity disorder, tic disorder, and allergy: is there a
      link? A nationwide population-based study.
AB  - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) and tic disorder
      usually co-occur in the same individuals, but the underlying mechanisms remain
      unclear. Previous evidence has shown that a frequent coexistence of allergic
      diseases was noted in patients with ADHD or tic disorder. We attempted to
      investigate the possible link among ADHD, tic disorder, and various allergic
      diseases. METHODS: Utilizing the Taiwan National Health Insurance Research
      Database from 1996 to 2010, 5,811 patients with ADHD alone, 1,816 patients with
      tic disorder alone, and 349 patients with dual diagnoses of ADHD and tic disorder
      were identified and compared with age-/gender-matched controls (1:4) in an
      investigation of the association among ADHD, tic disorder, and allergic diseases.
      RESULTS: Patients with dual diagnoses of ADHD and tic disorder had a
      significantly higher prevalence of allergic diseases and psychiatric
      comorbidities, including allergic rhinitis (43% vs. 28.4% vs. 33.6% vs. 19.7%, p
      < 0.001), asthma (27.5% vs. 17.2% vs. 18.2% vs. 11.9%, p < 0.001), atopic
      dermatitis (10.6% vs. 8.4% vs. 7.0 vs. 5.9%, p < 0.001), allergic conjunctivitis
      (55.6% vs. 34.7% vs. 43.5% vs. 26.3%, p < 0.001), obsessive compulsive disorder
      (4.0% vs. 1.3% vs. 2.0% vs. 0.1%, p < 0.001), and anxiety disorder (22.1% vs.
      18.0% vs. 6.0% vs. 0.5%, p < 0.001) than the ADHD alone group, the tic alone
      group, and the control group. Furthermore, ADHD patients with more allergic
      diseases (>= 3 comorbidities: OR: 3.73, 95% CI: 2.65~5.25; 2 comorbidities: OR:
      2.52, 95% CI: 1.82~3.47; 1 comorbidity: OR: 1.87, 95% CI: 1.41~2.49) exhibited an
      increased risk of tic disorder compared with ADHD patients without allergic
      disease. CONCLUSION:   A significant association among ADHD, tic disorder, and
      allergic diseases was noted in our study. The results may inspire further studies
      to clarify the underlying mechanisms and help us understand more about the
      complex etiology of ADHD, tic disorder, and their co-occurrence.

PMID- 23140274
TI  - Cost-effectiveness of rituximab in follicular lymphoma.
AB  - In advanced follicular lymphoma, rituximab is currently used with chemotherapy as
      induction therapy, and as maintenance monotherapy following induction in
      previously untreated patients and treatment-experienced relapsed/refractory
      patients. Herein, the authors characterize the clinical effectiveness, safety and
      cost-effectiveness of rituximab in follicular lymphoma, based on the literature
      review. Rituximab has a favorable safety profile and has been shown to improve
      progression-free survival, with some evidence of improvements to overall
      survival, particularly for relapsed/refractory patients. Rituximab has
      consistently been found to have a favorable economic profile, with cost per
      quality-adjusted life year falling within standard thresholds for cost
      effectiveness. Challenges in cost-effectiveness analysis include the fact that
      life expectancy for patients with follicular lymphoma exceeds the period of
      available follow-up data and that treatment pathways are more complex than the
      model structures frequently used in oncology models. As data accrue and more
      complex models are developed, the cost-effectiveness of rituximab can be more
      accurately assessed.

PMID- 23140276
TI  - Discomfort caused by low-frequency lateral oscillation, roll oscillation and roll
      compensated lateral oscillation.
AB  - Roll compensation during cornering (aligning the feet-to-head axis of the body
      with the resultant force) reduces lateral acceleration, but how any improvement
      in comfort depends on the frequency of the acceleration has not previously been
      investigated. Seated subjects judged the discomfort caused by lateral
      oscillation, roll oscillation and fully roll-compensated lateral oscillation at
      each of seven frequencies (0.25-1.0 Hz). Irrespective of whether it was caused by
      pure lateral acceleration or gravitational acceleration due to pure roll,
      acceleration in the plane of the seat caused similar discomfort at frequencies
      less than 0.4 Hz. From 0.4 to 1.0 Hz, with the same lateral acceleration in the
      plane of the seat, there was greater discomfort from roll oscillation than from
      lateral acceleration. With fully roll-compensated lateral oscillation, discomfort
      was less than with either the lateral component or the roll component of the
      motion from 0.2 to 0.5 Hz, but discomfort increased with increasing frequency and
      caused similar discomfort to pure roll oscillation at 1.0 Hz. PRACTITIONER
      SUMMARY: Tilting can reduce passenger exposure to vehicle lateral acceleration
      when cornering, but how comfort depends on the frequency of motion was unknown.
      This study shows 'tilt-compensation' only improves comfort at frequencies less
      than 0.5 Hz. The findings affect tilting vehicles and the prediction of
      discomfort caused by low-frequency motions.

PMID- 23140275
TI  - Synaptotagmin-like protein 4 and Rab8 interact and increase dense granule release
      in platelets.
AB  - BACKGROUND: Platelets are highly specialized cells that regulate hemostasis and
      thrombosis in the vasculature. Upon activation, platelets release various
      granules that impact on platelets, the coagulation system, other blood cells and
      the vessel wall; however, the mechanisms controlling granule release are only
      partially known. We have shown previously that synaptotagmin-like protein (Slp)1
      decreases dense granule release in platelets. OBJECTIVES: To determine the role
      of other Slps and their binding partners on platelet dense granule release.
      METHODS: RT-PCR and immunoblotting were used to identify Slps in human platelets.
      Interaction between Slp4 and Rab8 was investigated with pull-down assays,
      coimmunoprecipitation, and confocal microscopy. Secretion assays on permeabilized
      platelets were performed to investigate the effects of Slp4 and Rab8 on dense
      granule release. RESULTS:  Slp4 mRNA and protein are expressed in human
      platelets. Slp4 interacts with Rab8 in transfected cells and at endogenous
      protein levels in platelets. We mapped the Rab interaction site to the Slp
      homology domain of Slp4, and showed preferential binding of Slp4 to the GTP-bound
      form of Rab8. Live microscopy showed colocalization of green fluorescent protein
      Slp4 and mCherry-Rab8 at the plasma membrane of transfected cells. Endogenous
      platelet Slp4 and Rab8 colocalized in the center of activated platelets, where
      granule secretion takes place. Secretion assays revealed that Slp4 and Rab8
      enhance dense granule release and that the Slp4 effect is dependent on Rab8
      binding. CONCLUSIONS:  Slp4 and Rab8 are expressed and interact in human
      platelets, and might be involved in dense granule release.

PMID- 23140277
TI  - Specificity of the double-stranded RNA-binding domain from the RNA-activated
      protein kinase PKR for double-stranded RNA: insights from thermodynamics and
      small-angle X-ray scattering.
AB  - The interferon-inducible, double-stranded (ds) RNA-activated protein kinase (PKR)
      contains a dsRNA-binding domain (dsRBD) and plays key roles in viral pathogenesis
      and innate immunity. Activation of PKR is typically mediated by long dsRNA, and
      regulation of PKR is disfavored by most RNA imperfections, including bulges and
      internal loops. Herein, we combine isothermal titration calorimetry (ITC),
      electrophoretic mobility shift assays, and small-angle X-ray scattering (SAXS) to
      dissect the thermodynamic basis for the specificity of the dsRBD termed "p20" for
      various RNAs and to detect any RNA conformational changes induced upon protein
      binding. We monitor binding of p20 to chimeric duplexes containing terminal RNA
      DNA hybrid segments and a central dsRNA segment, which was either unbulged
      ("perfect") or bulged. The ITC data reveal strong binding of p20 to the perfect
      duplex (K(d) ~ 30 nM) and weaker binding to the bulged duplex (K(d) ~ 2-5 MUM).
      SAXS reconstructions and p(r) distance distribution functions further uncover
      that p20 induces no significant conformational change in perfect dsRNA but
      largely straightens bulged dsRNA. Together, these observations support the
      dsRBD's ability to tightly bind to only A-form RNA and suggest that in a
      noninfected cell, PKR may be buffered via weak interactions with various bulged
      and looped RNAs, which it may straighten. This work suggests that PKR-regulating
      RNAs with complex secondary and tertiary structures likely mimic dsRNA and/or
      engage portions of PKR outside of the dsRBD.

PMID- 23140278
TI  - Permeability reduction produced by grain reorganization and accumulation of
      exsolved CO2 during geologic carbon sequestration: a new CO2 trapping mechanism.
AB  - Carbon sequestration experiments were conducted on uncemented sediment and
      lithified rock from the Eau Claire Formation, which consisted primarily of K
      feldspar and quartz. Cores were heated to accentuate reactivity between fluid and
      mineral grains and to force CO(2) exsolution. Measured permeability of one
      sediment core ultimately reduced by 4 orders of magnitude as it was incrementally
      heated from 21 to 150  degrees C. Water-rock interaction produced some
      alteration, yielding sub-MUm clay precipitation on K-feldspar grains in the
      core's upstream end. Experimental results also revealed abundant newly formed
      pore space in regions of the core, and in some cases pores that were several
      times larger than the average grain size of the sediment. These large pores
      likely formed from elevated localized pressure caused by rapid CO(2) exsolution
      within the core and/or an accumulating CO(2) phase capable of pushing out
      surrounding sediment. CO(2) filled the pores and blocked flow pathways.
      Comparison with a similar experiment using a solid arkose core indicates that
      CO(2) accumulation and grain reorganization mainly contributed to permeability
      reduction during the heated sediment core experiment. This suggests that CO(2)
      injection into sediments may store more CO(2) and cause additional permeability
      reduction than is possible in lithified rock due to grain reorganization.

PMID- 23140279
TI  - Designed polyelectrolyte shell on magnetite nanocore for dilution-resistant
      biocompatible magnetic fluids.
AB  - Magnetite nanoparticles (MNPs) coated with poly(acrylic acid-co-maleic acid)
      polyelectrolyte (PAM) have been prepared with the aim of improving colloidal
      stability of core-shell nanoparticles for biomedical applications and enhancing
      the durability of the coating shells. FTIR-ATR measurements reveal two types of
      interaction of PAM with MNPs: hydrogen bonding and inner-sphere metal-carboxylate
      complex formation. The mechanism of the latter is ligand exchange between
      uncharged -OH groups of the surface and -COO(-) anionic moieties of the
      polyelectrolyte as revealed by adsorption and electrokinetic experiments. The
      aqueous dispersion of PAM@MNP particles (magnetic fluids - MFs) tolerates
      physiological salt concentration at composition corresponding to the plateau of
      the high-affinity adsorption isotherm. The plateau is reached at small amount of
      added PAM and at low concentration of nonadsorbed PAM, making PAM highly
      efficient for coating MNPs. The adsorbed PAM layer is not desorbed during
      dilution. The performance of the PAM shell is superior to that of poly(acrylic
      acid)  (PAA), often used in biocompatible MFs. This is explained by the different
      adsorption mechanisms; metal-carboxylate cannot form in the case of PAA.
      Molecular-level understanding of the protective shell formation on MNPs presented
      here improves fundamentally the colloidal techniques used in core-shell
      nanoparticle production for nanotechnology applications.

PMID- 23140280
TI  - Animal models of carcinogenesis in inflamed colorectum: potential use in
      chemoprevention study.
AB  - Inflammation is a risk factor for cancer development in several tissues. In the
      colorectum, inflammatory bowel disease (ulcerative colitis and Crohn's disease)
      is a longstanding inflammatory disease with increased risk for colorectal cancer
      (CRC). Several molecular events involving in chronic inflammatory process
      contribute to multi-stage carcinogenesis of CRC in the inflamed colon. They
      include alterations in production of reactive oxygen and nitrogen species,
      upregulation of pro-inflammatory cytokines and inflammatory enzymes, and
      intestinal immune system. In this short review, experimental animal models of
      inflammation-associated CRC are described. Also, some preclinical data on
      chemoprevention of inflammation-associated CRC by astaxanthin and a specific
      inhibitor of nitric oxide synthase using these inflammation-related CRC models is
      briefly introduced.

PMID- 23140281
TI  - Single dose oral pharmacokinetic profile of alpha-mangostin in mice.
AB  - The mangosteen fruit (Garcinia mangostana) is a rich source of dietary xanthones
      with the most prominent being alpha-mangostin. Dietary xanthones have been
      reported to have a variety of health promoting properties. Until now, in vivo
      studies on the pharmacokinetic profile of alpha-mangostin are limited. For this
      study we employed an LC/MS/MS assay to determine the pharmacokinetic properties
      of alpha-mangostin suspension in cottonseed oil in C57BL/6 Mice. Mice were
      administered 100 mg/kg of alpha-mangostin by oral gavage and the plasma levels
      were analyzed over a 24 hour period. We observed the degree of exposure (i.e.
      area under the curve) of alpha-mangostin to be 5,736 nmol/L/hr and the maximum
      plasma concentration was 1,382 nmol/L. Furthermore, we provide evidence that
      alpha-mangostin undergoes glucuronidation into monoglucuronide and diglucuronide
      metabolites. Our study demonstrated that alpha-mangostin when administered in
      cotton seed oil to mice at a dose equivalent to 615 mg in a 90kg human adult
      achieves an approximate maximum plasma concentration of 1,300 nmol/L and is
      detectable for up to 24 hours. Further research is needed to understand the
      relationship between the pharmacokinetic properties of alpha-mangostin following
      oral administration and reported health benefits.

PMID- 23140282
TI  - Indole compounds against breast cancer: recent developments.
AB  - Breast cancer is still the leading cause of cancer deaths among women worldwide
      and new therapies and drugs are continuously being conceived and explored to
      better control or even cure this disease. Among the most efficacious low
      molecular drugs for the treatment of breast cancer are indole derivatives such as
      3,3'-diindolylmethane (DIM), the structurally complex antimitotic vinca
      alkaloids, and the synthetic receptor tyrosine kinase inhibitor sunitinib. This
      review is to give an insight into the latest developments in the field of indole
      based drugs against breast cancers with a focus on those derived from natural
      products and on their targets and modes of action. Pertinent literature is
      covered from 2007 up to 2012.

PMID- 23140283
TI  - Anticarcinogenic actions of tributyrin, a butyric acid prodrug.
AB  - Bioactive food compounds (BFCs) exhibit potential anticarcinogenic effects that
      deserve to be explored. Butyric acid (BA) is considered a promising BFC and has
      been used in clinical trials; however, its short half-life considerably restricts
      its therapeutic application. Tributyrin (TB), a BA prodrug present in milk fat
      and honey, has more favorable pharmacokinetic properties than BA, and its oral
      administration is also better tolerated. In vitro and in vivo studies have shown
      that TB acts on multiple anticancer cellular and molecular targets without
      affecting non-cancerous cells. Among the TB mechanisms of action, the induction
      of apoptosis and cell differentiation and the modulation of epigenetic mechanisms
      are notable. Due to its anticarcinogenic potential, strategies as lipid
      emulsions, nanoparticles, or structured lipids containing TB are currently being
      developed to improve its organoleptic characteristics and bioavailability. In
      addition, TB has minimal toxicity, making it an excellent candidate for
      combination therapy with other agents for the control of cancer. Despite the lack
      of data available in the literature, TB is a promising molecule for anticancer
      strategies. Therefore, additional preclinical and clinical studies should be
      performed using TB to elucidate its molecular targets and anticarcinogenic
      potential.

PMID- 23140284
TI  - Ent-11alpha-hydroxy-15-oxo-kaur-16-en-19-oic-acid induces apoptosis of human
      malignant cancer cells.
AB  - Ent-11alpha-hydroxy-15-oxo-kaur-16-en-19-oic-acid (5F) is a chemical compound
      isolated from Pteris semipinnata L (PsL), a Chinese traditional herb. 5F has been
      known to exert antitumor activity in several kinds of human malignant cancer
      cells by leading cancer cell to apoptosis. 5F translocated Bax into the
      mitochondria, down-regulated Bcl-2, activated caspase-9 and caspase-3, released
      cytochrome c into the cytosol and translocated AIF from the mitochondria to the
      nucleus. The presentation of a wild-type p53 in the cancer cells facilitated
      cancer cells sensitive to the 5F treatment. 5F induces apoptosis of cancer cells
      by inhibiting NF-kappaB activation/induction, which leading to the decrease of
      Bcl-2 but the increase of Bax and Bak. MAPK kinases and Akt are also involved in
      process of 5F inducing cancer cell apoptosis. In lung cancer, 5F activated ERK1/2
      and the inhibition of ERK1/2 suppressed 5F-mediated changes in apoptotic
      molecules. 5F activated Akt and suggested that Akt activation was anti-apoptotic
      rather than pro-apoptotic. However, in anaplastic thyroid carcinoma, JNK
      activation was related to cell death induced by 5F. ERK and p38 were also
      activated but as survival signals in response to 5F treatment to counteract the
      induction of cell death. Collectively, 5F is effective against several malignant
      cancers both in vivo and in vitro with minimal side effects. It induces apoptosis
      through the mitochondrialmediated pathway, in which regulation of Bcl-2 family
      proteins expression, the activation of MAPK and inactivation of NF-kappaB are
      critical. The good ability of 5F to inhibit cancer cells makes it in line with
      the successful development of other anti-tumor agents.

PMID- 23140285
TI  - A prooxidant mechanism for the anticancer and chemopreventive properties of plant
      polyphenols.
AB  - Plant-derived polyphenols, a prominent class of phytochemicals, are considered
      important components of human diet. A number of them are known to possess
      chemopreventive and therapeutic properties against various diseases including
      cancer. Several studies using cancer cell lines and animal models of
      carcinogenesis have shown that a wide range of polyphenols possess anticancer and
      apoptosis-inducing properties. Notably, an important aspect of the
      chemopreventive action of polyphenols is their differential activity in
      selectively targeting cancer cells while sparing normal cells. However, the
      mechanism through which polyphenols modulate their cancer cell selective
      anticancer effects has not been clearly delineated. In this regard,
      identification of a definitive anticancer mechanism of polyphenols would
      contribute to establish them as potent lead compounds for the synthesis of novel
      anticancer drugs. Although polyphenols are generally recognized as antioxidants,
      they also act as prooxidants inducing DNA degradation in the presence of metal
      ions such as copper. Based on our own observations and those of others, a
      mechanism for the anticancer properties of polyphenols that involves mobilization
      of chromatin-bound copper and consequent prooxidant action leading to cell death,
      was proposed. Since it is known that tissue and cellular copper levels are
      significantly elevated in a number of malignancies, cancer cells would be more
      subject to redox cycling between copper ions and polyphenols to generate reactive
      oxygen species (ROS) responsible for DNA breakage. This review discusses such a
      copper-dependent prooxidant mechanism of action of polyphenols that accounts for
      their observed chemopreventive properties, as also for their preferential
      cytotoxicity towards cancer cells.

PMID- 23140287
TI  - Ascorbic acid in cancer chemoprevention: translational perspectives and efficacy.
AB  - Chemoprevention, which is referred to as the use of nontoxic natural or synthetic
      chemicals to intervene in multistage carcinogenesis has since decades attracted a
      considerable interest in plant-derived chemical constituents often termed as
      "phytochemicals" or sometimes as "Nutraceuticals" in case they are derived from
      dietary sources. A comprehensive search of the literature show that such an
      interest in natural product pharmacology has surged in the last 25 years and
      particularly risen at exponential rates since the last one decade. Phytochemicals
      such as curcumin (from spice turmeric), resveratrol (from red wine) and genistein
      (from soy) share the major efforts as indicated by overwhelming publications,
      despite skepticism concerning their bioavailability. Ascorbic acid (AA), the
      popular anti-oxidant in fruits and vegetables, has even a longer historical
      perspective than these dietary agents as for more than 35 years; there had been
      lingering questions about the efficacy of AA in cancer therapy. The footprints of
      AA from "scurvy" to "cancer" though complex seems to carry potential provided the
      puzzle could be set right. The use of AA in cancer treatment has been debated
      extensively as evident from the literature but surprisingly the complementing
      early phase bench work on the mechanistic studies for anticancer action was
      rather retarded. Proposed mechanisms of action for AA in the prevention and
      treatment of cancer includes antioxidant as well as pro-oxidant properties,
      stimulation of the immune system, altering carcinogen metabolism, enhancement of
      collagen synthesis necessary for tumor encapsulation and interference with cancer
      cell signaling. The observation that the intravenous administration of AA
      enhances its bioavailability to the extent of deriving pharmacological benefits
      against cancer has in recent years partially supported the clinical plausibility
      (efficacy) of AA towards realizing its translational advantage. Here, we provide
      an overview of AA with regard to its potential in the management of cancer
      disease.

PMID- 23140286
TI  - Genistein inhibits cell growth and induces apoptosis through up-regulation of miR
      34a in pancreatic cancer cells.
AB  - Pancreatic cancer (PC) is the fourth most common cause of cancer-related deaths
      in the United States, suggesting that designing novel therapeutic strategy is
      required to improve the survival outcome of patients diagnosed with PC. Recently,
      microRNAs (miRNA) have been found to be involved in the regulation of multiple
      aspects of tumor development and progression including PC. In this study, we
      investigate whether miR-34a plays a critical role in the control of cell growth
      and apoptosis in PC cells. We found that Re-expression (forced expression) of miR
      34a inhibits cell growth and induces apoptosis, with concomitant down-regulation
      of Notch-1 signaling pathway, one of the target of miR-34a. Moreover, treatment
      of PC cells with a natural compound genistein led to the up-regulation of miR
      34a, resulting in the down-regulation of Notch-1, which was correlated with
      inhibition of cell growth, and induction of apoptosis. Our findings suggest that
      genistein could function as a non-toxic activator of a miRNA that can suppress
      the proliferation of PC cells.

PMID- 23140288
TI  - Baicalein--an intriguing therapeutic phytochemical in pancreatic cancer.
AB  - Despite advances in therapy for many of the most common cancers, advances which
      have led to corresponding improvements in survival rates, progress on the
      pancreatic cancer front have been slow and mortality rates remain startlingly
      high. New therapeutic strategies are needed. Phytochemicals are naturally
      occurring, plant-based substances that have garnered much interest in the
      research world for their anti-cancer properties, both as therapeutics and as
      components of the diet for chemoprevention. One particularly ubiquitous group of
      phytochemicals is the polyphenolic flavonoids. Baicalein, one such flavonoid,
      which has been widely studied in several malignancies, shows potent activity
      against pancreatic adenocarcinoma in both in vitro and in vivo studies. The
      mechanisms by which baicalein accomplishes this have recently been elucidated,
      and is through an induction of apoptosis in pancreatic cancer cells that are
      fiercely resistant to cell death. Compounds such as baicalein, offer promise in
      dietary chemoprevention, as chemotherapeutic adjuvants, or as targeted therapy.

PMID- 23140289
TI  - From body art to anticancer activities: perspectives on medicinal properties of
      henna.
AB  - Nature has been a rich source of therapeutic agents for thousands of years and an
      impressive number of modern drugs have been isolated from natural sources based
      on the uses of these plants in traditional medicine. Henna is one such plant
      commonly known as Persian Henna or Lawsonia inermis, a bushy, flowering tree,
      commonly found in Australia, Asia and along the Mediterranean coasts of Africa.
      Paste made from the leaves of Henna plant has been used since the Bronze Age to
      dye skin, hairs and fingernails especially at the times of festivals. In recent
      times henna paste has been used for body art paintings and designs in western
      countries. Despite such widespread use in dyeing and body art painting, Henna
      extracts and constituents possess numerous biological activities including
      antioxidant, anti-inflammatory, antibacterial and anticancer activities. The
      active coloring and biologically active principle of Henna is found to be Lawsone
      (2- hydroxy-1, 4-naphthoquinone) which can serve as a starting building block for
      synthesizing large number of therapeutically useful compounds including
      Atovaquone, Lapachol and Dichloroallyl lawsone which have been shown to possess
      potent anticancer activities. Some other analogs of Lawsone have been found to
      exhibit other beneficial biological properties such as antioxidant, anti
      inflammatory, antitubercular and antimalarial. The ability of Lawsone to undergo
      the redox cycling and chelation of trace metal ions has been thought to be
      partially responsible for some of its biological activities. Despite such diverse
      biological properties and potent anticancer activities the compound has remained
      largely unexplored and hence in the present review we have summarized the
      chemistry and biological activities of Lawsone along with its analogs and metal
      complexes.

PMID- 23140290
TI  - Chemopreventive and chemotherapeutic potential of curcumin in breast cancer.
AB  - Breast cancer remains the leading cause of cancer death among females worldwide.
      It signifies a shift from the previous decade during which the most common cause
      of cancer death was cervical cancer. Current treatment modalities, including
      surgery, radiotherapy, and adjuvant chemotherapy or hormone therapy, have not
      been successful enough to impart significant improvement in the morbidity or
      mortality of breast cancer. This cancer is highly resistant to chemotherapy as no
      effective treatment exists for advanced disease conditions. Moreover, there is a
      dearth of ideal protein biomarkers of breast cancer in plasma or serum that can
      be used with desired sensitivity and specificity. Along with the existing
      therapeutic modalities of breast cancer the focus of researchers and clinicians
      have shifted towards the exploration of the preventive and therapeutic uses of
      natural products, including dietary phytoconstituents. Curcumin, the principal
      active component of Indian curry spice turmeric, has been found to exert
      preventive and therapeutic effects in various cancers. This is, in part, due to
      its ability to influence a diverse range of molecular targets and signaling
      pathways. The ability of curcumin to enhance the efficacy of existing
      chemotherapeutic agents is an added advantage. The current review critically
      analyzes various aspects of curcumin-related research conducted for molecular
      understanding of its efficacy in in vitro and in vivo models of breast cancer.
      The article also highlights recent developments with synthetic analogs of
      curcumin and nanocurcumin which are in the horizon of next generation targeted
      therapy with curcumin in breast cancer.

PMID- 23140291
TI  - Apigenin Modulates Insulin-like Growth Factor Axis: Implications for Prevention
      and Therapy of Prostate Cancer.
AB  - Aberrant changes to the insulin-like growth factor (IGF) axis promote prostate
      cancer development and progression, adaptation for growth and survival in a
      castrate environment, and invasive metastasis. Natural and/or synthetic compounds
      that target the IGF axis to prevent or reverse theses abnormalities may be
      extremely useful in the chemoprevention and/or chemotherapy of prostate cancer.
      Apigenin, a naturally-occurring flavone found in many fruits and vegetables, is
      one such compound that can correctively modulate the IGF axis to induce growth
      arrest and apoptosis in many pre-clinical in vitro and in vivo models of prostate
      cancer. Because of its known mechanism of action, low toxicity, and effectiveness
      at physiologically relevant levels in animal models of prostate cancer, apigenin
      is an excellent candidate for a pilot study to determine the effect of apigenin
      supplementation on prostate cancer development and progression in humans.

PMID- 23140292
TI  - Mitosis-targeting natural products for cancer prevention and therapy.
AB  - Mitosis is a complex process resulting in division of a cell into two daughter
      cells, and its failure often results in the death of the daughter cells (via
      apoptotic, necrotic, or proliferative/senescent death). Many chemicals that
      inhibit the mitotic process (anti-mitotic drugs) have proven effective for
      killing cancer cells in vitro and in clinical settings. Among the most studied
      anti-mitotic drugs are plant-origin natural products including taxanes (e.g.
      paclitaxel, docetaxel) and vinca alkaloids (e.g. vincristine, vinblastine), whose
      validated target is the spindle microtubules. With the success of these agents,
      efforts have been made to develop other spindle poisons as well as to improve
      efficacy of existing spindle poisons with structural modifications. Novel drugs
      and natural products that inhibit other proteins involved in mitosis
      (nonmicrotubule targets) have been sought in hopes of expanding available cancer
      directed therapies. Recently, significant advances have been made in the
      understanding of mitotic mechanisms in tumor cells as well as in normal
      epithelial cells. These advances help us to identify and develop potential
      natural agents for the prevention and treatment of cancer. This review will focus
      on natural products that target mitotic process and/or proteins involved in
      mitotic progression.

PMID- 23140294
TI  - Cancer chemoprevention with green tea catechins: from bench to bed.
AB  - Many epidemiological studies and a large number of experimental studies using a
      variety of animal models have observed that consumption or administration of
      green tea appears to exert cancer chemopreventive activity. Based on the results
      of numerous laboratory cell culture investigations, several mechanisms have been
      hypothesized to underlie the anti-cancer activity of green tea catechins,
      especially that of (-)-epigallocatechin-3-gallate (EGCG), the most abundant and
      active constituent in green tea. These mechanisms include promotion of anti
      oxidant activity, inhibition of NF-kappaB and AP-1, regulation of the cell cycle,
      inhibition of receptor tyrosine kinase pathways, control of epigenetic
      modifications, and modulation of the immune system. Several recent interventional
      studies examining the anti-carcinogenic properties of green tea catechins in
      humans have yielded promising results that suggest the possibility of their
      application to human clinical trials. This review article analyzes the results of
      these studies to explicate the effects of consumption or administration of green
      tea and its constituents on malignancies observed to date and discuss future
      directions in this research field.

PMID- 23140293
TI  - Apoptosis and autophagy induction as mechanism of cancer prevention by naturally
      occurring dietary agents.
AB  - Nontoxic naturally occurring compounds, especially those from dietary sources,
      are receiving increasing consideration for prevention and treatment of diseases
      including cancer. There is a growing need for innovative anticancer therapies and
      therefore search for natural compounds with novel biological activities or
      antineoplastic potential is currently an important area in drug discovery.
      Support for this interest also comes from increasing concern over the efficacy
      and safety of many conventional therapies, especially those that run over a long
      course of time. Laboratory studies in different in vitro and in vivo systems have
      shown that many natural compounds possess the capacity to regulate response to
      oxidative stress and DNA damage, suppress angiogenesis, inhibit cell
      proliferation and induce autophagy and apoptosis. This review discusses the
      induction of apoptosis and autophagy as a mechanism of cancer prevention by some
      of the most studied naturally occurring dietary compounds.

PMID- 23140296
TI  - DIMming ovarian cancer growth.
AB  - Ovarian cancer is the leading gynecologic malignancy with more than 22,000 new
      cases and 15,000 deaths estimated each year. It is usually detected in late
      stages with poor prognosis due to lack of sufficiently accurate screening tests.
      Epidemiological studies continue to support the notion that consumption of
      cruciferous vegetables reduces the risk of ovarian cancer. In the present review
      article, we describe the anti-cancer effects of 3, 3'-diindolylmethane (DIM), a
      compound present in cruciferous vegetables, against ovarian cancer. DIM targets
      multiple aspects of cancer such as cellcycle regulation and survival, including
      EGFR-JAK2-STAT3 signaling, checkpoint activation, caspase activation, endoplasmic
      reticulum stress, autophagy and anoikis. This broad spectrum of anti-cancer
      activities in conjunction with low systemic toxicity accentuates the
      translational value of DIM in cancer therapy. Together, our pre-clinical studies
      demonstrate that DIM has activity against ovarian cancer and hence should be
      further investigated in clinical setting to exploit its therapeutic potential.

PMID- 23140297
TI  - Bioavailability challenges associated with development of saponins as therapeutic
      and chemopreventive agents.
AB  - Saponins, a major class of natural phytochemicals, hold great promises for being
      developed into chemopreventive and chemotherapeutic drugs. However, one of the
      major factors limiting their pharmacological effects in vivo is poor
      bioavailability. This paper reviews the factors that determine the absorption and
      bioavailability of saponins including their physicochemical properties, and their
      absorption and disposition in the gastrointestinal tract. A critical review of
      the current research papers suggests that poor permeability and microflora
      hydrolysis of saponins are the primary factors that limit their
      bioavailabilities. Future investigations should be directed towards further
      optimization of the bioavailability of saponins to enhance their chemopreventive
      and chemotherapeutic effects in vivo.

PMID- 23140295
TI  - Targeting CSC-related miRNAs for cancer therapy by natural agents.
AB  - The theory of cancer stem cells (CSCs) has provided evidence on fundamental
      clinical implications because of the involvement of CSCs in cell migration,
      invasion, metastasis, and treatment resistance, which leads to the poor clinical
      outcome of cancer patients. Therefore, targeting CSCs will provide a novel
      therapeutic strategy for the treatment and/or prevention of tumors. However, the
      regulation of CSCs and its signaling pathways during tumorigenesis are not well
      understood. MicroRNAs (miRNAs) have been proved to act as key regulators of the
      post-transcriptional regulation of genes, which involve in a wide array of
      biological processes including tumorigenesis. The altered expressions of miRNAs
      are associated with poor clinical outcome of patients diagnosed with a variety of
      tumors. Therefore, emerging evidence strongly suggest that miRMAs play critical
      roles in tumor development and progression. Emerging evidence also suggest that
      miRNAs participate in the regulation of tumor cell growth, migration, invasion,
      angiogenesis, drug resistance, and metastasis. Moreover, miRNAs such as let-7,
      miR-21, miR-22, miR-34, miR-101, miR-146a, and miR-200 have been found to be
      associated with CSC phenotype and function mediated through targeting oncogenic
      signaling pathways. In this article, we will discuss the role of miRNAs in the
      regulation of CSC phenotype and function during tumor development and
      progression. We will also discuss the potential role of naturally occurring
      agents (nutraceuticals) as potent anti-tumor agents that are believed to function
      by targeting CSC-related miRNAs.

PMID- 23140298
TI  - Medicinal properties of the Jamaican pepper plant Pimenta dioica and Allspice.
AB  - The Caribbean tropical tree, Pimenta dioica has been used for a variety of human
      endeavors, such as in perfumery industry, food spice, as a natural pesticide, and
      in folk medicine. Discovered in Jamaica during the voyages of Christopher
      Columbus, the dried unripe berries of P. dioica also known as Allspice can be
      found in all continents with unique names in over 50 languages. Systematic
      investigation of aromatic constituents of Pimenta leaves and its unripe berries,
      Allspice, have resulted in discovery of many and novel aromatic compounds, mostly
      glycosides and polyphenols that show antibacterial, hypotensive, anti-neuralgic
      and analgesic properties. Recent studies have shown two of the known compounds
      isolated from Allspice, Eugenol and Gallic acid have selective antiproliferative
      and anti-tumor properties on human cancer cells and their animal models. New
      characterization of novel compounds such as Ericifolin from the aqueous extract
      of Allspice berries show potent anti-prostate cancer and anti-breast cancer
      properties that can be verified in vitro as well as in vivo. Considering its
      purity, mostly available as "organically grown" berries, availability at low
      cost, wide acceptance in culinary delights of many cultures world-wide, Allspice
      may have an additional space in most households, in their medicine cabinets.

PMID- 23140299
TI  - Androgen receptor in human health: a potential therapeutic target.
AB  - Androgen is a key for the activation of Androgen Receptor (AR) in most of the
      disease conditions, however androgen-independent activation of AR is also found
      in aggressive type human malignancies. An intense search for the inhibitors of AR
      is underway to cure AR-dependent diseases. In addition to targeting various
      components of AR signaling pathway, compounds which directly target AR are under
      preclinical and clinical investigation. Various In vitro and preclinical animal
      studies suggest that different natural compounds have potential to act against
      AR. Some natural compounds have been found to be pharmacologically effective
      against AR irrespective of varying routs of administration viz; oral, intra
      peritoneal and intravenous. This mini-review summarizes the studies conducted
      with different natural agents in determining their pharmacological utility
      against AR signaling.

PMID- 23140300
TI  - The therapeutic value of natural agents to treat miRNA targeted breast cancer in
      African-American and Caucasian-American women.
AB  - Breast cancer is the most common cancer in women in the United States, with
      African-American (AA) women showing significantly higher rates than Caucasian
      American (CA) women do. The reason for this racial disparity remains unknown, and
      factors that might be responsible for the differences in incidence and mortality
      have not been identified. One possible factor could be microRNAs (miRs), which
      are small noncoding regulatory RNAs involved intimately in cancer, and the
      expression of certain miRs may be decreased or increased in the breast tumors of
      AA and CA women. Therefore, modulation of miRs using natural agents could lead to
      the development of a novel therapeutic strategy to treat aggressive forms of
      breast cancer in women of different racial backgrounds. The function of natural
      agents in the regulation of miRs has not been investigated extensively. In this
      review, we will discuss the potential role of naturally occurring agents as
      potent antitumor agents thought to function by targeting miRs as contributing
      factors to the disparity in breast cancer between AA and CA women.

PMID- 23140301
TI  - Editorial: translational implications of natural agents.

PMID- 23140303
TI  - Generalizability theory for the perplexed: a practical introduction and guide:
      AMEE Guide No. 68.
AB  - BACKGROUND: Generalizability theory (G theory) is a statistical method to analyze
      the results of psychometric tests, such as tests of performance like the
      Objective Structured Clinical Examination, written or computer-based knowledge
      tests, rating scales, or self-assessment and personality tests. It is a
      generalization of classical reliability theory, which examines the relative
      contribution of the primary variable of interest, the performance of subjects,
      compared to error variance. In G theory, various sources of error contributing to
      the inaccuracy of measurement are explored. G theory is a valuable tool in
      judging the methodological quality of an assessment method and improving its
      precision. AIM: Starting from basic statistical principles, we gradually develop
      and explain the method. We introduce tools to perform generalizability analysis,
      and illustrate the use of generalizability analysis with a series of common,
      practical examples in educational practice. CONCLUSION: We realize that
      statistics and mathematics can be either boring or fearsome to many physicians
      and educators, yet we believe that some foundations are necessary for a better
      understanding of generalizability analysis. Consequently, we have tried, wherever
      possible, to keep the use of equations to a minimum and to use a conversational
      and slightly "off-serious" style.

PMID- 23140304
TI  - Quality evaluation reports: Can a faculty development program make a difference?
AB  - BACKGROUND: The quality of medical student and resident clinical evaluation
      reports submitted by rotation supervisors is a concern. The effectiveness of
      faculty development (FD) interventions in changing report quality is uncertain.
      AIMS: This study assessed whether faculty could be trained to complete higher
      quality reports. METHOD: A 3-h interactive program designed to improve evaluation
      report quality, previously developed and tested locally, was offered at three
      different Canadian medical schools. To assess for a change in report quality,
      three reports completed by each supervisor prior to the workshop and all reports
      completed for 6 months following the workshop were evaluated by three blinded,
      independent raters using the Completed Clinical Evaluation Report Rating (CCERR):
      a validated scale that assesses report quality. RESULTS: A total of 22
      supervisors from multiple specialties participated. The mean CCERR score for
      reports completed after the workshop was significantly higher (21.74 +/- 4.91
      versus 18.90 +/- 5.00, p = 0.02). CONCLUSIONS: This study demonstrates that this
      FD workshop had a positive impact upon the quality of the participants'
      evaluation reports suggesting that faculty have the potential to be trained with
      regards to trainee assessment. This adds to the literature which suggests that FD
      is an important component in improving assessment quality.

PMID- 23140305
TI  - Values add value: an online tool enhances postgraduate evidence-based practice
      learning.
AB  - BACKGROUND: To better prepare practitioners for the complex world of clinical
      decision-making, teaching evidence-based practice needs to move beyond its focus
      on skills and knowledge to give students an experience and understanding of
      applying evidence in practice. AIM: To explore whether incorporating an online
      values-based tool enhanced learning in a post graduate epidemiology course.
      METHODS: Having completed a critical appraisal of an epidemiological study,
      students were asked to then respond to a case scenario, using the analytical
      frameworks of the Values-Exchange, a software tool that highlights ethical
      domains in decision-making. The student experience of the Values-Exchange was
      evaluated using focus groups. Sessions were audiotaped and transcribed. In total,
      613 responses were analysed by two independent coders to identify emergent
      themes. RESULTS: Three main themes emerged: (1) the Values-Exchange exposed
      students to new concepts and ideas relating to healthcare decision-making; (2)
      the diversity of other student values broadened their perspectives and (3) the
      experience brought reality to what it means to apply evidence in practice.
      CONCLUSION: Adding an online values-based tool to clinical epidemiology teaching
      was highly valued by students and enabled new understandings of empirical
      evidence and its application in practice.

PMID- 23140302
TI  - Tight junctions at the blood brain barrier: physiological architecture and
      disease-associated dysregulation.
AB  - The Blood-brain barrier (BBB), present at the level of the endothelium of
      cerebral blood vessels, selectively restricts the blood-to-brain paracellular
      diffusion of compounds; it is mandatory for cerebral homeostasis and proper
      neuronal function. The barrier properties of these specialized endothelial cells
      notably depend on tight junctions (TJs) between adjacent cells: TJs are dynamic
      structures consisting of a number of transmembrane and membrane-associated
      cytoplasmic proteins, which are assembled in a multimolecular complex and acting
      as a platform for intracellular signaling. Although the structural composition of
      these complexes has been well described in the recent years, our knowledge about
      their functional regulation still remains fragmentary. Importantly, pericytes,
      embedded in the vascular basement membrane, and perivascular microglial cells,
      astrocytes and neurons contribute to the regulation of endothelial TJs and BBB
      function, altogether constituting the so-called neurovascular unit.The present
      review summarizes our current understanding of the structure and functional
      regulation of endothelial TJs at the BBB. Accumulating evidence points to a
      correlation between BBB dysfunction, alteration of TJ complexes and progression
      of a variety of CNS diseases, such as stroke, multiple sclerosis and brain
      tumors, as well as neurodegenerative diseases like Parkinson's and Alzheimer's
      diseases. Understanding how TJ integrity is controlled may thus help improve drug
      delivery across the BBB and the design of therapeutic strategies for neurological
      disorders.

PMID- 23140306
TI  - Students' perception of a modified form of PBL using concept mapping.
AB  - BACKGROUND: Problem-based learning (PBL) and concept mapping have been shown to
      promote active and meaningful learning. AIM: To design a method of PBL that
      includes concept mapping and examine students' perceptions of this form of PBL.
      METHODS: We designed a 5-phase method of PBL which produced three clearly
      identifiable mapping phases that reflected the learning activities during the
      tutorial: (1) the initial understanding of the clinical problem, (2) students'
      prior knowledge of the problem, (3) the final understanding of the problem
      following self-directed study. The process of developing the second and third
      phases of the map involved the students answering questions that they generated
      on two occasions to give the entire process a 5-phase approach. Each student was
      exposed to both methods of PBL: a conventional 7-step method (Maastricht type)
      and the modified PBL (5-phase) method. We used a questionnaire to evaluate the
      students' perceptions of the two methods in four learning domains. RESULT: The
      students' ratings for the 5-phase method were significantly higher than for the 7
      step method (paired t-test) on all items on the questionnaire. CONCLUSION: The
      students perceived the 5-phase method as promoting their passion for learning,
      and developing their cognitive, metacognitive and interpersonal skills.

PMID- 23140308
TI  - The dependence between clinical condition and value of the maximum force in the
      quadriceps femoris muscle during MVC test in patients with knee osteoarthritis.
AB  - The aim of this study was to check whether there was a correlation between the
      value of the maximum developed torque of the quadriceps femoris muscle and
      subjective evaluation of a patient's pain which is measured by the VAS. Also
      evaluated were changes in the muscle torque value and KSS scale over time. For
      examining patient's condition use was made of a KSS scale (knee score: pain,
      range of motion, stability of joint and limb axis) before the surgery and in
      weeks 6 and 12, as well as 6 months after surgery. It was found to be constantly
      improving in comparison with the condition before the surgery. This is confirmed
      by a significant statistical value difference of KSS scale. The surgery
      substantially increases the quality of live and function recurrence.

PMID- 23140307
TI  - Lysyl oxidase may play a critical role in hypoxia-induced NSCLC cells invasion
      and migration.
AB  - Lysyl oxidase (LOX), a copper-dependent amine oxidase known to function both
      intracellularly and extracellularly, is implicated in promoting tumor progression
      and hypoxic metastasis in certain malignancies. Nonsmall cell lung cancer (NSCLC)
      is a highly aggressive cancer with poor prognosis worldwide. However, the role
      and molecular mechanism by which LOX involving in hypoxic NSCLC invasion and
      migration are poorly understood. This study explores the effect of LOX on
      invasion and migration of NSCLC cells under hypoxic conditions. Small interfering
      RNA (siRNA) targeting LOX was used to silence LOX expression of hypoxic NSCLC
      cells, SPCA1 and A549. Cellular invasive and migratory potentials were determined
      by matrigel invasion and migration assays. Expression of LOX, Src, Src activation
      (Tyr418 phosphorylation of Src), and Snail were evaluated by real-time PCR and
      western blot, respectively. The results showed that LOX mRNA and protein
      expression were upregulated under hypoxic conditions in NSCLC cells. Knockdown of
      LOX led to inhibition of hypoxia-induced invasion and migration. Phosphorylated
      Src (Tyr418) and Snail proteins were decreased along with LOX downregulation. Our
      data provide molecular evidences that LOX is mechanistically linked to increased
      invasion and migration of hypoxic NSCLC cells, and may serve as an antimetastasis
      target of human NSCLC.

PMID- 23140309
TI  - Relationships between DFT/RRKM branching ratios of the complementary fragment
      ions [C5H5O]+ and [M - C5H5O]+ and relative abundances in the EI mass spectrum of
      N-(2-furylmethyl)aniline.
AB  - The energy-dependent branching ratios of the complementary fragment ions
      [C(5)H(5)O](+) and [HC(6)H(4)NH](+) ([M - C(5)H(5)O](+)), originating from the N
      (2-furylmethyl)aniline molecular ion, [HC(6)H(4)NH-C(5)H(5)O](+*), were obtained
      from Rice-Ramsperger-Kassel-Marcus (RRKM) rate calculations based on density
      functional theory (DFT) energy profiles. The UB3LYP/6-311G+(3df,2p)//UB3LYP/6
      31G(d) level of theory was used to model the competitive reaction mechanisms by
      which the molecular ion can be fragmented. Initially, eight pairs of products
      were taken into account, corresponding to the combination of two isomeric
      structures for each fragment ion and the concomitant radicals, which can be
      formed by direct dissociations or through some isomerization-fragmentation
      pathways. A great deal of the obtained pathways was discarded by looking over the
      kinetic barrier heights and the individual RRKM rate coefficients calculated for
      all the steps. This way, the potential energy profiles were simplified to only
      three reaction channels, two pathways to [C(5)H(5)O](+) and one to [M -
      C(5)H(5)O](+). The pre-equilibrium and steady-state approximations were then
      applied to different regions of the remaining potential energy profiles, allowing
      the branching ratios of the complementary fragment ions to be easily calculated
      and discriminated among the three rival processes. According to these results,
      the major fragment ion in the ion source is [C(5)H(5)O](+), which is produced as
      a mixture of two structures, the furfuryl and pyrylium cations, one formed by a
      direct C-N bond cleavage and the other through an isomerization-fragmentation
      channel. In turn, the direct fragmentation is the only mechanism to produce [M -
      C(5)H(5)O](+). To confront these results with the available experimental
      information, the model was broadened out to the 4-substituted analogues [4-R
      C(6)H(4)NH-C(5)H(5)O](+*) in which R = F, Br, Cl, CH(3), and OCH(3), finding
      excellent correlations of the calculated branching ratios and the relative
      abundances in the electron ionization mass spectra.

PMID- 23140310
TI  - Contamination of nanoparticles by endotoxin: evaluation of different test
      methods.
AB  - BACKGROUND: Nanomaterials can be contaminated with endotoxin
      (lipopolysaccharides, LPS) during production or handling. In this study, we
      searched for a convenient in vitro method to evaluate endotoxin contamination in
      nanoparticle samples. We assessed the reliability of the commonly used limulus
      amebocyte lysate (LAL) assay and an alternative method based on toll-like
      receptor (TLR) 4 reporter cells when applied with particles (TiO(2), Ag, CaCO(3)
      and SiO(2)), or after extraction of the endotoxin as described in the ISO norm
      29701. RESULTS: Our results indicate that the gel clot LAL assay is easily
      disturbed in the presence of nanoparticles; and that the endotoxin extraction
      protocol is not suitable at high particle concentrations. The chromogenic-based
      LAL endotoxin detection systems (chromogenic LAL assay and Endosafe-PTS), and the
      TLR4 reporter cells were not significantly perturbed. CONCLUSION: We demonstrated
      that nanoparticles can interfere with endotoxin detection systems indicating that
      a convenient test method must be chosen before assessing endotoxin contamination
      in nanoparticle samples.

PMID- 23140311
TI  - Searching for gene expression differences in primary fibroblasts between patients
      with one and two neoplasms in childhood.
AB  - Genetic factors are important for developing primary and subsequent malignancies
      in children. This study investigated the role of genetic factors involved in DNA
      repair. Designed as a feasibility study, it addressed the possibility of
      obtaining samples for genetic analyses from former patients through the German
      Childhood Cancer Registry. Testing feasibility was as important as the biological
      question itself. We analyzed the expression of DNA-repair genes in untreated
      primary fibroblasts of 20 individuals with a second neoplasm compared to 20
      matched single neoplasm cases using customized cDNA microarrays (1344 gene
      sequences, about 800 genes). Matching was by first neoplasm, age, and year of
      first diagnosis. Forty-six percent of the 52 contacted second neoplasm cases and
      18% of the 132 single neoplasm patients participated in the study. The DNA-repair
      gene results show small differences in the basal gene expression of FTH1 and
      CDKN1A. To our knowledge, this is the first study using gene expression arrays in
      untreated primary fibroblasts regarding second neoplasms after a childhood
      neoplasm. We were able to recruit childhood cancer patients for genetic analyses
      long after diagnosis. The biological importance of the differences in the DNA
      repair gene expression has to be elucidated yet.

PMID- 23140312
TI  - Healthcare provider attitudes towards the problem list in an electronic health
      record: a mixed-methods qualitative study.
AB  - BACKGROUND: The problem list is a key part of the electronic health record (EHR)
      that allows practitioners to see a patient's diagnoses and health issues. Yet, as
      the content of the problem list largely represents the subjective decisions of
      those who edit it, patients' problem lists are often unreliable when shared
      across practitioners. The lack of standards for how the problem list is compiled
      in the EHR limits its effectiveness in improving patient care, particularly as a
      resource for clinical decision support and population management tools. The
      purpose of this study is to discover practitioner opinions towards the problem
      list and the logic behind their decisions during clinical situations. MATERIALS
      AND METHODS: An observational cross-sectional study was conducted at two major
      Boston teaching hospitals. Practitioners' opinions about the problem list were
      collected through both in-person interviews and an online questionnaire.
      Questions were framed using vignettes of clinical scenarios asking practitioners
      about their preferred actions towards the problem list. RESULTS: These data
      confirmed prior research that practitioners differ in their opinions over
      managing the problem list, but in most responses to a questionnaire, there was a
      common approach among the relative majority of respondents. Further, basic
      demographic characteristics of providers (age, medical experience, etc.) did not
      appear to strongly affect attitudes towards the problem list. CONCLUSION: The
      results supported the premise that policies and EHR tools are needed to bring
      about a common approach. Further, the findings helped identify what issues might
      benefit the most from a defined policy and the level of restriction a problem
      list policy should place on the addition of different types of information.

PMID- 23140313
TI  - Case clusters of leproid granulomas in foxhounds in New Zealand and Australia.
AB  - BACKGROUND: Canine leproid granuloma (CLG) characteristically presents as single
      to multiple circumscribed dermal to subcutaneous nodules in haired skin. An
      unidentified mycobacterium is considered be the aetiological agent of this
      entity. ANIMALS: Several cases of canine leproid granulomas occurred in dogs in
      New Zealand during 2010 and 2011. Cases appeared in clusters, affecting multiple
      closely related foxhounds domiciled in the same kennels. All affected hounds
      recovered after topical and/or systemic antimicrobial therapy. Two similar
      outbreaks that occurred in foxhounds near Melbourne, Australia are also reported.
      METHODS: Cases were investigated using cytological, histological, microbiological
      and several molecular techniques. An environmental epidemiological study was also
      performed. RESULTS: A diagnosis of CLG was established in 11 dogs. Molecular
      identification of the causative agent confirmed that it was a mycobacterial
      species with 100% sequence homology within the amplified regions of the 16S rRNA
      gene and internal transcribed spacer (ITS1) with that found in association with
      similar infections from the USA, Brazil and Australia. CONCLUSION AND CLINICAL
      IMPORTANCE: This report details the first occurrence of multiple cases of CLG
      occurring in in-contact dogs and the first proven case of CLG in dogs in New
      Zealand.

PMID- 23140314
TI  - Ciclosporin therapy is associated with minimal changes in calcium metabolism in
      dogs with atopic dermatitis.
AB  - BACKGROUND: Ciclosporin is widely used in the management of canine atopic
      dermatitis. In humans, ciclosporin therapy has been linked to disturbances in
      calcium metabolism and resultant skeletal disorders. OBJECTIVES: The objective of
      this study was to assess calcium homeostasis in dogs before and after a 6 week
      course of once daily oral ciclosporin at the licensed dose (5 mg/kg). ANIMALS:
      Sixteen client-owned dogs with spontaneous atopic dermatitis. METHODS: Serum
      concentrations of calcium, phosphate, creatinine, 25-hydroxyvitamin D, 1,25
      dihyroxyvitamin D and plasma concentrations of ionized calcium and parathyroid
      hormone (PTH) were measured, together with the urinary fractional excretion of
      calcium and phosphate. The extent of skin lesions was scored using the Canine
      Atopic Dermatitis Extent and Severity Index (CADESI)-03 and the degree of
      pruritus by the Edinburgh Pruritus Scale prior to and at the end of the study.
      RESULTS: The CADESI-03 and the Edinburgh Pruritus Scale scores decreased
      satisfactorily in all dogs by the end of the study. Plasma PTH concentrations
      were significantly increased (P = 0.02) following ciclosporin treatment, whereas
      all other biochemical parameters were not significantly different from their
      starting values. The increase in PTH was mild in most cases and the proportion of
      dogs that had a PTH concentration above the reference range was not significantly
      different following treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: This study
      indicates that ciclosporin has minimal impact on calcium metabolism in dogs with
      atopic dermatitis when used at the licensed and clinically effective dosage for 6
      weeks.

PMID- 23140315
TI  - Dermatophagoides farinae house dust mite allergen challenges reduce stratum
      corneum ceramides in an experimental dog model of acute atopic dermatitis.
AB  - BACKGROUND: Ceramides are essential stratum corneum (SC) lipids and they play a
      pivotal role in maintaining effective cutaneous barrier function. OBJECTIVES: The
      present study aimed at determining the effect of a Dermatophagoides farinae house
      dust mite (Df-HDM) allergen challenge on SC ceramides of atopic dogs
      experimentally sensitized to these allergens. ANIMALS: Six Df-HDM-sensitized
      atopic Maltese-beagle dogs were used. METHODS: Prechallenge SC was obtained by
      cyanoacrylate stripping. One week later, the dogs were challenged topically with
      Df-HDM allergens, which resulted in mild to moderate inflammation 24 h later. Two
      weeks after challenge, SC of lesional and nonlesional skin was obtained. Finally,
      SC was collected from challenge sites 2 months after lesion resolution. The
      different SC lipids were quantified blindly by thin-layer chromatography.
      RESULTS: Significantly lower amounts of ceramides [AH], [AP], [AS], [NP], [EOP],
      [NS] and [EOS] were observed in lesional SC compared with prechallenge samples,
      while no significant effect was found on the amount of other lipids, including
      cholesterol and free fatty acids. The ceramide profile of nonlesional skin
      generally showed the same postchallenge reduction pattern. Ceramide amounts
      returned to normal within 2 months after lesion remission. CONCLUSION AND
      CLINICAL IMPORTANCE: These findings suggest that the allergic reactions caused by
      Df-HDM allergens lead to a selective reduction of SC ceramides, not only at sites
      of inflammation but also at sites away from those of allergen application. There
      is normalization of ceramide amounts after inflammation subsides. These
      observations suggest that the deficiency of ceramides observed in canine atopic
      skin occurs, at least in part, secondary to inflammation.

PMID- 23140316
TI  - Characterization of the inflammatory infiltrate and cytokine expression in the
      skin of horses with recurrent urticaria.
AB  - BACKGROUND: Recurrent urticaria (RU) is a common skin disease of horses, but
      little is known about its pathogenesis. HYPOTHESIS/OBJECTIVE: The aim of this
      study was to characterize the inflammatory cell infiltrate and cytokine
      expression pattern in the skin of horses with RU. ANIMALS:   Biopsies of lesional
      and nonlesional skin of horses with RU (n = 8) and of skin from healthy control
      horses (n = 8) were evaluated. METHODS: The inflammatory cell infiltrate was
      analysed by routine histology. Immunohistochemistry was used to identify T cells
      (CD3), B  ells (CD79), macrophages (MAC387) and mast cells (tryptase). Expression
      of T-helper 2 cytokines (interleukins IL-4, IL-5 and IL-13), a T-helper 1
      cytokine (interferon-gamma), IL-4 receptor alpha and thymic stromal lymphopoietin
      was assessed by quantitative RT-PCR. Results -  In subepidermal lesional skin of
      RU-affected horses, increased numbers of eosinophils (P <= 0.01), CD79-positive
      (P <= 0.01), MAC387-positive (P <= 0.01) and tryptase-positive cells (P <= 0.05)
      were found compared with healthy horses. Subepidermal lesional skin of RU
      affected horses contained more eosinophils (P <= 0.05) and tryptase-positive
      cells (P <= 0.05) compared with nonlesional skin. There was no significant
      difference in infiltrating cells between nonlesional skin and skin of healthy
      horses. Expression of IL-4 (P <= 0.01), IL-13 (P <= 0.05), thymic stromal
      lymphopoietin (P <= 0.05) and IL-4 receptor alpha (P <= 0.05) was increased in
      lesional skin of RU-affected horses compared with control horses. Expression of
      IL-4 was higher (P <= 0.05) in lesional compared with nonlesional RU skin.
      CONCLUSIONS AND CLINICAL IMPORTANCE: Analysis of cytokine expression and
      inflammatory infiltrate suggests that T-helper 2 cytokines, eosinophils, mast
      cells and presumptive macrophages play a role in the pathogenesis of equine RU.

PMID- 23140317
TI  - Phylogenetic relationships in three species of canine Demodex mite based on
      partial sequences of mitochondrial 16S rDNA.
AB  - BACKGROUND: The historical classification of Demodex mites has been based on
      their hosts and morphological features. Genome sequencing has proved to be a very
      effective taxonomic tool in phylogenetic studies and has been applied in the
      classification of Demodex. Mitochondrial 16S rDNA has been demonstrated to be an
      especially useful marker to establish phylogenetic relationships.
      HYPOTHESIS/OBJECTIVES: To amplify and sequence a segment of the mitochondrial 16S
      rDNA from Demodex canis and Demodex injai, as well as from the short-bodied mite
      called, unofficially, D. cornei and to determine their genetic proximity.
      METHODS: Demodex mites were examined microscopically and classified as Demodex
      folliculorum (one sample), D. canis (four samples), D. injai (two samples) or the
      short-bodied species D. cornei (three samples). DNA was extracted, and a 338 bp
      fragment of the 16S rDNA was amplified and sequenced. RESULTS: The sequences of
      the four D. canis mites were identical and shared 99.6 and 97.3% identity with
      two D. canis sequences available at GenBank. The sequences of the D. cornei
      isolates were identical and showed 97.8, 98.2 and 99.6% identity with the D.
      canis isolates. The sequences of the two D. injai isolates were also identical
      and showed 76.6% identity with the D. canis sequence. CONCLUSION: Demodex canis
      and D. injai are two different species, with a genetic distance of 23.3%. It
      would seem that the short-bodied Demodex mite D. cornei is a morphological
      variant of D. canis.

PMID- 23140318
TI  - Development and validation of the Canine Atopic Dermatitis Lesion Index, a scale
      for the rapid scoring of lesion severity in canine atopic dermatitis.
AB  - BACKGROUND: The third iteration of the Canine Atopic Dermatitis Extent and
      Severity Index (CADESI-03) is the only tool rigorously validated for canine
      atopic dermatitis (CAD) lesion scoring. The CADESI-03 requires 248 evaluations,
      limiting its widespread use. HYPOTHESIS/OBJECTIVES: The goal of the study was to
      develop and validate a practical method of grading CAD lesions that requires
      scoring only the frequently affected body regions. ANIMALS: Fifty-seven privately
      owned atopic dogs were used in the study. METHODS: The Canine Atopic Dermatitis
      Lesion Index (CADLI) was evaluated in an open, multicentre reliability study.
      Validity was assessed with expert opinion (content validity) and comparison of
      CADLI with existing disease severity measures (construct and criterion validity).
      Reliability was evaluated by analysing repeated observations of each dog.
      Convenience was assessed in terms of the time required to complete the scale.
      RESULTS: The CADLI scores correlated with overall assessment scores (r = 0.60, P
      < 0.001, linear mixed model) and pruritus severity scores (r = 0.53, P < 0.001,
      linear mixed model), establishing construct validity. The CADLI was strongly
      correlated with CADESI-03 (r = 0.84, P < 0.001, linear mixed model), establishing
      criterion validity. The CADLI values obtained by two observers correlated very
      strongly (r = 0.91, P < 0.001), as did the repeat values for the same observer (r
      = 0.98, P < 0.001). The mean time to complete the CADLI was less than that
      required for CADESI-03 (1.9 and 12.6 min, respectively), a highly significant
      difference (P < 0.001). CONCLUSION AND CLINICAL IMPORTANCE: The CADLI was found
      to be an effective measure of CAD lesion severity, strongly correlating with
      CADESI-03. The convenience of CADLI makes it suitable for use in both clinical
      research and practice.

PMID- 23140319
TI  - A case of apparent canine erysipeloid associated with Erysipelothrix
      rhusiopathiae bacteraemia.
AB  - BACKGROUND: Erysipelothrix rhusiopathiae is a Gram-positive facultative anaerobe
      found worldwide and is most commonly associated with skin disease in swine, while
      anecdotal reports of cases in dogs have been associated with endocarditis.
      HYPOTHESIS/OBJECTIVES: Clinicians should consider systemic infectious diseases as
      a potential cause of erythematous skin lesions. ANIMALS: A 5-year-old female
      spayed Labrador retriever presented with lethargy, anorexia and erythematous skin
      lesions while receiving immunosuppressive therapy for immune-mediated haemolytic
      anaemia. Four days prior to presentation, the dog had chewed on a raw turkey
      carcase. METHODS: Complete blood count, serum chemistry profile, urinalysis and
      blood cultures. RESULTS: Blood cultures yielded a pure growth of E. rhusiopathiae
      serotype 1b. Amoxicillin 22 mg/kg orally twice daily for 2 weeks and
      discontinuation of azathioprine resulted in remission of fever and skin lesions.
      CONCLUSIONS AND CLINICAL IMPORTANCE: This report is the first documentation, to
      the best of the authors' knowledge, of Erysipelothrix infection, a known
      zoonosis, in an immunosuppressed dog, highlighting the need for infectious
      disease monitoring in patients receiving such therapy. This information may also
      help educate veterinarians to include Erysipelothrix infection as a differential
      diagnosis in dogs with fever and skin lesions, as well as the role of blood
      cultures in diagnosing this disease.

PMID- 23140320
TI  - Interaction of Piscidin-1 with zwitterionic versus anionic membranes: a
      comparative molecular dynamics study.
AB  - Plasma membrane of each micro-organism has a unique set of lipid composition as a
      consequence of the environmental adaptation or a response to exposure to
      antimicrobial peptides (AMPs) as antibiotic agents. Understanding the
      relationship between lipid composition and action of antimicrobial peptides or
      considering how different lipid bilayers respond to AMPs may help us design more
      effective peptide drugs in the future. In this contribution, we intend to
      elucidate how two currently used membrane models, namely palmitoyl-oleoyl
      phosphtidylglycerol (POPG) and 1-palmitoyl-oleoyl-glycero-phosphocholine (POPC),
      respond to antimicrobial peptide Piscidin-1 (Pis-1).The computed density profile
      of the peptide as it moves from the bulk solvent toward the membrane core
      suggests that Pis-1 penetrates into the POPG bilayer less than the POPC membrane.
      Furthermore, we showed that the two model membranes used in this study have
      different behavior in the presence of Pis-1. Hence, we suggest that membrane
      composition could be an important factor in determining lytic ability of peptide
      drugs to kill a unique bacterial species.

PMID- 23140322
TI  - New editorial crew.

PMID- 23140321
TI  - A human MYBPC3 mutation appearing about 10 centuries ago results in a
      hypertrophic cardiomyopathy with delayed onset, moderate evolution but with a
      risk of sudden death.
AB  - BACKGROUND: Hypertrophic Cardiomyopathy (HCM) is a genetically heterogeneous
      disease. One specific mutation in the MYBPC3 gene is highly prevalent in center
      east of France giving an opportunity to define the clinical profile of this
      specific mutation. METHODS: HCM probands were screened for mutation in the MYH7,
      MYBPC3, TNNT2 and TNNI3 genes. Carriers of the MYBPC3 IVS20-2A>G mutation were
      genotyped with 8 microsatellites flanking this gene. The age of this MYBPC3
      mutation was inferred with the software ESTIAGE. The age at first symptom,
      diagnosis, first complication, first severe complication and the rate of sudden
      death were compared between carriers of the IVS20-2 mutation (group A) and
      carriers of all other mutations (group B) using time to event curves and log rank
      test. RESULTS: Out of 107 HCM probands, 45 had a single heterozygous mutation in
      one of the 4 tested sarcomeric genes including 9 patients with the MYBPC3 IVS20
      2A>G mutation. The IVS20-2 mutation in these 9 patients and their 25 mutation
      carrier relatives was embedded in a common haplotype defined after genotyping 4
      polymorphic markers on each side of the MYBPC3 gene. This result supports the
      hypothesis of a common ancestor. Furthermore, we evaluated that the mutation
      occurred about 47 generations ago, approximately at the 10th century.We then
      compared the clinical profile of the IVS20-2 mutation carriers (group A) and the
      carriers of all other mutations (group B). Age at onset of symptoms was similar
      in the 34 group A cases and the 73 group B cases but group A cases were diagnosed
      on average 15 years later (log rank test p = 0.022). Age of first complication
      and first severe complication was delayed in group A vs group B cases but the
      prevalence of sudden death and age at death was similar in both groups.
      CONCLUSION: A founder mutation arising at about the 10th century in the MYBPC3
      gene accounts for 8.4% of all HCM in center east France and results in a
      cardiomyopathy starting late and evolving slowly but with an apparent risk of
      sudden death similar to other sarcomeric mutations.

PMID- 23140323
TI  - An inverse approach for the mechanical characterisation of vascular tissues via a
      generalised rule of mixtures.
AB  - Mechanical factors such as stresses and strains play a major role in the growth
      and remodelling of soft biological tissues. The main constituents of tissue
      undergo different processes reacting to mechanical stimulus. Thereby, the
      characterisation of growth and remodelling requires an accurate estimation of the
      stresses and strains of their main components. Many soft tissues can be
      considered as composite materials and can be analysed using an appropriate rule
      of mixtures. Particularly, arterial tissue can be modelled as an isotropic soft
      matrix reinforced with preferentially oriented collagen fibres. An inverse
      approach to obtain the mechanical characterisation of each main component is
      proposed in this work. The procedure is based on a rule of mixtures raised in a
      finite deformation framework and generalised to include kinematics and
      compatibility equations for serial-parallel behaviour. This methodology allows
      obtaining the stress-strain relationship of the components fitting experimental
      data.

PMID- 23140326
TI  - Physiological responses of Police Officers during job simulations wearing
      chemical, biological, radiological and nuclear personal protective equipment.
AB  - The aim of this study was to quantify the physiological responses of Police
      Officers wearing chemical, biological, radiological and nuclear personal
      protective equipment (CBRN PPE) during firearms house entry (FE) unarmed house
      entry (UE) and crowd control (CC) simulations. Participants volunteered from the
      UK Police Force [FE (n = 6, age 33 +/- 4 years, body mass 85.3 +/- 7.9 kg,
      (.)VO2max 53 +/- 5 ml . kg-1 . min-1), UE and CC (n = 11, age 34 +/- 5 years,
      body mass 88.5 +/- 13.8 kg, (.)VO2max 51 +/- 5 ml . kg-1 . min-1)]. Heart rate
      reserve (HRR) during FE was greater than UE (74 +/- 7 vs. 62 +/- 6%HRR, p = 0.01)
      but lower in CC (39 +/- 7%HRR, p < 0.01). Peak core body temperature was greater
      during FE (39.2 +/- 0.3 degrees C) than UE (38.9 +/- 0.4 degrees C, p < 0.01) and
      CC (37.5 +/- 0.3 degrees C, p < 0.01), with similar trends in skin temperature.
      There were no differences in the volume of water consumed (1.13 +/- 0.44 l, p =
      0.51) or change in body mass (-1.68 +/- 0.65 kg, p = 0.74) between simulations.
      The increase in body temperature was a primary physiological limitation to
      performance. Cooling strategies and revised operating procedures may improve
      Police Officers' physical performance while wearing CBRN PPE. PRACTITIONER
      SUMMARY: In recent years, the likelihood of Police Officers having to respond to
      a chemical, biological, nuclear or radiological (CBRN) incident wearing personal
      protective equipment (PPE) has increased. Such apparel is likely to increase
      physiological strain and impair job performance; understanding these limitations
      may help improve Officer safety and operational effectiveness.

PMID- 23140327
TI  - Enzymatic and chemical interesterification of rice bran oil, sheaolein, and palm
      stearin and comparative study of their physicochemical properties.
AB  - Total of 3 different mixtures of rice bran oil (RBO), sheaolein (SO), and palm
      stearin (PS) (RBO : SO : PS, 40 : 35 : 25; 15 : 40 : 45; 10 : 35 : 55) were
      modified by enzymatic interesterification (EIE) using TLIM as a bio-catalyst.
      After interesterification, a physicochemical properties of selected ratio (10 :
      35 : 55; RBO : SO : PS) was compared with chemical interesterification (CIE). CIE
      sample showed higher SFC than EIE in each measured temperature. DAG content was
      lower in CIE than EIE sample. Besides, each EIE or CIE products were compared
      with blends, where higher SFC, longer induction time was observed in the blends.
      Oxidative stability was measured based on Rancimat and peroxide value (PV) where
      EIE sample showed longer induction time and lower PV compared to CIE sample.
      Further, EIE sample was selected for oxidation studies and kept at 60  degrees C
      for 22 d after the addition of antioxidants (EGCG, rosemary) where induction time
      was significantly increased compared to control. EGCG containing sample showed
      longer induction time and lower PV compared to rosemary containing sample.

PMID- 23140328
TI  - Copper phosphonatoethanesulfonates: temperature dependent in situ energy
      dispersive X-ray diffraction study and influence of the pH on the crystal
      structures.
AB  - The system Cu(2+)/H2O3P-C2H4-SO3H/NaOH was investigated using in situ energy
      dispersive X-ray diffraction (EDXRD) to study the formation and temperature
      induced phase transformation of previously described copper phosphonosulfonates.
      Thus, the formation of [Cu2(O3P-C2H4-SO3)(OH)(H2O)].3H2O (4) at 90  degrees C is
      shown to proceed via a previously unknown intermediate [Cu2(O3P-C2H4
      SO3)(OH)(H2O)].4H2O (6), which could be structurally characterized from high
      resolution powder diffraction data. Increase of the reaction temperature to 150 
      degrees C led to a rapid phase transformation to [Cu2(O3P-C2H4-SO3)(OH)(H2O)].H2O
      (1), which was also studied by in situ EDXRD. The comparison of the structures of
      1, 4, and 6 allowed us to establish a possible reaction mechanism. In addition to
      the in situ crystallization studies, microwave assisted heating for the synthesis
      of the copper phosphonosulfonates was employed, which allowed the growth of
      larger crystals of [NaCu(O3P-C2H4-SO3)(H2O)2] (5) suitable for single crystal X
      ray diffraction. Through the combination of force field calculations and Rietveld
      refinement we were able to determine the crystal structure of [Cu1.5(O3P-C2H4
      SO3)] 2H2O (3) and thus structurally characterize all compounds known up to now
      in this well investigated system. With the additional structural data we are now
      able to describe the influence of the pH on the structure formation. 

PMID- 23140329
TI  - Differential effects of the hydrophobic surfactant proteins on the formation of
      inverse bicontinuous cubic phases.
AB  - Prior studies have shown that the biological mixture of the two hydrophobic
      surfactant proteins, SP-B and SP-C, produces faster adsorption of the surfactant
      lipids to an air/water interface, and that they induce 1-palmitoyl-2-oleoyl
      phosphatidylethanolamine (POPE) to form inverse bicontinuous cubic phases.
      Previous studies have shown that SP-B has a much greater effect than SP-C on
      adsorption. If the two proteins induce faster adsorption and formation of the
      bicontinuous structures by similar mechanisms, then they should also have
      different abilities to form the cubic phases. To test this hypothesis, we
      measured small-angle X-ray scattering on the individual proteins combined with
      POPE. SP-B replicated the dose-related ability of the combined proteins to induce
      the cubic phases at temperatures more than 25  degrees C below the point at which
      POPE alone forms the curved inverse-hexagonal phase. With SP-C, diffraction from
      cubic structures was either absent or present at very low intensities only with
      larger amounts of protein. The correlation between the structural effects of
      inducing curved structures and the functional effects on the rate of adsorption
      fits with the model in which SP-B promotes adsorption by facilitating formation
      of an inversely curved, rate-limiting structure.

PMID- 23140330
TI  - Association of a missense mutation in the luteinizing hormone/choriogonadotropin
      receptor gene (LHCGR) with superovulation traits in Chinese Holstein heifers.
AB  - BACKGROUND: Upon binding luteinizing hormone in the ovary, the luteinizing
      hormone/choriogonadotropin receptor (LHCGR) is necessary for follicular
      maturation and ovulation, as well as luteal function. We detected mutations in
      the LHCGR gene and evaluated their association with superovulation. METHODS:
      Using polymerase chain reaction-single strand conformation polymorphism (PCR
      SSCP) and DNA sequencing, we examined polymorphisms in LHCGR and the genotypes
      associated with superovulation traits in 127 Chinese Holstein heifers. RESULTS: A
      G/T polymorphism (ss52050737) in exon 11 was significantly associated with the
      total number of ova and the number of transferable embryos. CONCLUSIONS: LHCGR
      may be a new predictor for superovulation in Chinese Holstein heifers.

PMID- 23140331
TI  - A systems pharmacokinetic and pharmacodynamic approach to identify opportunities
      and pitfalls in energy stress-mediated chemoprevention: the use of metformin and
      other biguanides.
AB  - Metformin, a widely used anti-hyperglycemic drug in the biguanide class, is
      currently under investigation for the prevention of cancer. Surprisingly however,
      considering the time and cost of clinical chemoprevention trials and the current
      scrutiny of cancer chemoprevention, limited attention has been given to
      integrating available data, identifying the subpopulations most likely to
      benefit, or to quantitatively understanding the potential pitfalls of biguanide
      chemoprevention. Herein, a physiologically-based pharmacokinetic (PBPK) and
      pharmacodynamic framework is proposed for integrating information on
      physicochemical, cell-based, animal, and human studies of various biguanides to
      identify gaps in knowledge and to build a systems model that may facilitate the
      planning of randomized cancer chemoprevention trials of metformin.

PMID- 23140333
TI  - Protein nanopore-based, single-molecule exploration of copper binding to an
      antimicrobial-derived, histidine-containing chimera peptide.
AB  - Metal ions binding exert a crucial influence upon the aggregation properties and
      stability of peptides, and the propensity of folding in various substates.
      Herein, we demonstrate the use of the alpha-HL protein as a powerful nanoscopic
      tool to probe Cu(2+)-triggered physicochemical changes of a 20 aminoacids long,
      antimicrobial-derived chimera peptide with a His residue as metal-binding site,
      and simultaneously dissect the kinetics of the free- and Cu(2+)-bound peptide
      interaction to the alpha-HL pore. Combining single-molecule electrophysiology on
      reconstituted lipid membranes and fluorescence spectroscopy, we show that the
      association rate constant between the alpha-HL pore and a Cu(2+)-free peptide is
      higher than that of a Cu(2+)-complexed peptide. We posit that mainly due to
      conformational changes induced by the bound Cu(2+) on the peptide, the resulting
      complex encounters a higher energy barrier toward its association with the
      protein pore, stemming most likely from an extra entropy cost needed to fit the
      Cu(2+)-complexed peptide within the alpha-HL lumen region. The lower dissociation
      rate constant of the Cu(2+)-complexed peptide from alpha-HL pore, as compared to
      that of Cu(2+)-free peptide, supports the existence of a deeper free energy well
      for the protein interaction with a Cu(2+)-complexed peptide, which may be
      indicative of specific Cu(2+)-mediated contributions to the binding of the Cu(2+)
      complexed peptide within the pore lumen.

PMID- 23140334
TI  - Application of muscle model to the musculoskeletal modeling.
AB  - The purpose of this paper is to investigate new fusiform muscle models. Each of
      these models treats a muscle as a system composed of parts characterized by
      different mechanical properties. These models explain the influence of
      differences in the stiffness of lateral parts and the degree of muscle model
      discretization. Each muscle model is described by a system of differential
      equations and a single integro-differential equation. Responses of fifty-four
      muscle model forms are examined using a complex exertion composed of three types:
      eccentric-concentric exertion, isokinetic-isometric exertion and step exertion.

PMID- 23140332
TI  - Principles underlying the use of multiple informants' reports.
AB  - Researchers use multiple informants' reports to assess and examine behavior.
      However, informants' reports commonly disagree. Informants' reports often
      disagree in their perceived levels of a behavior ("low" versus "elevated" mood),
      and examining multiple reports in a single study often results in inconsistent
      findings. Although researchers often espouse taking a multi-informant assessment
      approach, they frequently address informant discrepancies using techniques that
      treat discrepancies as measurement error. Yet, recent work indicates that
      researchers in a variety of fields often may be unable to justify treating
      informant discrepancies as measurement error. In this review, the authors advance
      a framework (Operations Triad Model) outlining general principles for using and
      interpreting informants' reports. Using the framework, researchers can test
      whether or not they can extract meaningful information about behavior from
      discrepancies among multiple informants' reports. The authors provide supportive
      evidence for this framework and discuss its implications for hypothesis testing,
      study design, and quantitative review.

PMID- 23140335
TI  - Vibration analysis of the sulky accessory for a commercial walk-behind lawn mower
      to determine operator comfort and health.
AB  - A sulky is a single-wheeled platform attachment on which the operator of a
      commercial walk-behind lawn mower rides while standing. The effects of sulky
      vibration on operator comfort and health have not been investigated. In this
      study, tri-axial accelerometers measured sulky vibration during mower use by two
      commercial mowers on varied terrain and 12 volunteer mowers over a controlled
      course. The accelerometer data were processed according to methods established in
      ISO 2631. Results indicate the mean frequency-weighted root mean square (RMS)
      acceleration sums fall into the 'very uncomfortable' range for vibration of
      standing persons (1.9 +/- 0.48 m s-2). Additionally, vibration dose values
      indicated that the mean vibration dosages exceeded the daily exposure limit
      values established in Directive 2002 /44/EC (z-axis A(8) value of 1.30 +/- 34 m s
      2; VDV(exp) value of 28.1 +/- 6.25 m s-1.75). This information suggests that
      modifications including vibration damping should be added to the sulky to reduce
      rider discomfort and health risks. PRACTITIONER SUMMARY: This study investigated
      the effects of vibration during use of a commercial lawn mowing sulky. Findings
      from accelerometer data suggest that the vibration experienced by sulky operators
      is significant enough to cause discomfort and health risks which may lead to
      personnel turnover or long-term effects for the operator.

PMID- 23140336
TI  - Primary cerebral radiotherapy-induced rhabdomyosarcoma: treatment with
      intraoperative carmustine implants.
AB  - INTRODUCTION: Primary cerebral rhabdomyosarcomas (cRMS) are extremely rare, with
      only 41 cases reported in the literature. Survival of patients with localized
      cRMS is 70% after 5 years but not in the case of intracranial neoplasms, where
      survival rarely exceeds 10 months. CASE REPORT: A 10-year-old female patient with
      a history of acute lymphoblastic leukemia (ALL) and holocranial radiotherapy (RT)
      6 years ago, referred after partial surgical resection of a left parietal lesion,
      diagnosed as an embryonal tumor with mixed neuronal-glial differentiation (WHO
      grade IV). A second operation was performed for complete resection and placement
      of intracavitary chemotherapy (carmustine). The pathology revealed a high-grade
      undifferentiated neoplasm positive for myogenin and desmin that was compatible
      with cRMS. In the immunohistochemistry study, the neoplasm was positive for
      vimentin, myogenin, and desmin, as is characteristic of cRMS, and negative for
      synaptophysin and enolase, ruling out primitive neuroectodermal embriogenic tumor
      (PNET). Given a diagnosis of cRMS, a combined thoracoabdominal PET-CT scan was
      performed without finding other primary lesions and a bone marrow study was also
      performed without observing abnormalities. Consequently, the diagnosis was
      established as primary cRMS. DISCUSSION: Among the long-term sequelae of
      radiotherapy, neurocognitive disorders, brain disorders such as leukomalacia,
      vascular diseases, or secondary tumors, ranging from benign lesions such as
      meningiomas to more aggressive lesions such as ependymomas, which are high-grade
      gliomas, are described. In the brain MRI, our patient showed a radiotherapy
      induced periventricular leukomalacia and a malignant lesion: a cRMS. The use of
      carmustine in this disease may facilitate local control.

PMID- 23140337
TI  - Elucidating electronic transitions from sigma orbitals of liquid n- and branched
      alkanes by far-ultraviolet spectroscopy and quantum chemical calculations.
AB  - Attenuated total reflection far-ultraviolet (ATR-FUV) spectra containing Rydberg
      states of n-alkanes (C(m)H(2m+2); m varies in the range 5-9) and branched alkanes
      observed in the liquid phase were investigated by quantum chemical calculations
      with the aim of elucidating electronic transitions from sigma orbitals of liquid
      n- and branched alkanes. New assignments are proposed based on the time-dependent
      density functional theory (TD-DFT) and symmetry-adapted cluster configuration
      interaction (SAC-CI) calculations, and the differences in these spectra are
      analyzed in detail. The FUV spectra of n-alkanes show a broad asymmetric feature
      near 8.3 eV. The strong band at ~8.3 eV shows a red shift with a significant
      increase in intensity as the carbon chain length increases, which is attributed
      to the overlapping transitions from the third (or fourth) highest occupied
      molecular orbitals HOMO-2 (or HOMO-3) and HOMO-1 to Rydberg 3p(y) by the TD-DFT
      and SAC-CI calculations. This band was previously assigned to the overlap of two
      peaks arising from the transition from the HOMO to 3p and from the HOMO-1 to 3s
      based on their term values. Although the most intense transition, T1, is from
      HOMO-2 for m = 5 and 6 and HOMO-3 for m varying in the range of 7-9, the shape of
      Kohn-Sham molecular orbital for T1 is similar among the all-alkanes investigated.
      The theoretical result also has demonstrated that the red shift originates in
      both stabilization of the Rydberg 3p(y) and destabilization of the occupied
      orbitals. The intensity of the shoulder at 7.7 eV drastically increases in the
      spectra of the branched alkanes, especially for those with quaternary carbon
      atoms such as 2,2-dimethyl butane. This increase in intensity is caused by a
      reduction in symmetry in the branched alkanes, which leads the forbidden
      transitions to Rydberg 3s to allowed transitions. In this way, the present study
      has provided new insight into the existence of their Rydberg transitions and the
      shape of the relevant MOs of the transitions.

PMID- 23140338
TI  - Individual differences in the efficacy of a short theory of mind intervention for
      children with autism spectrum disorder: a randomized controlled trial.
AB  - BACKGROUND: Having a 'theory of mind', or having the ability to attribute mental
      states to oneself or others, is considered one of the most central domains of
      impairment among children with an autism spectrum disorder (ASD). Many
      interventions focus on improving theory of mind skills in children with ASD.
      Nonetheless, the empirical evidence for the effect of these interventions is
      limited. The main goal of this study is to examine the effectiveness of a short
      theory of mind intervention for children with ASD. A second objective is to
      determine which subgroups within the autism spectrum profit most from the
      intervention. METHODS: This study is a randomized controlled trial. One hundred
      children with ASD, aged 7 to 12 years will be randomly assigned to an
      intervention or a waiting list control group. Outcome measures include the
      completion of theory of mind and emotion understanding tasks, and parent and
      teacher questionnaires on children's social skills. Follow-up data for the
      intervention group will be collected 6 months after the interventions.
      DISCUSSION: This study evaluates the efficacy of a theory of mind intervention
      for children with ASD. Hypotheses, strengths, and limitations of the study are
      discussed. TRIAL REGISTRATION: Netherlands Trial Register NTR2327.

PMID- 23140339
TI  - Impact of roasting on the chemical composition and oxidative stability of perilla
      oil.
AB  - The impact of roasting was observed with regard to certain changes in the
      chemical components and oxidative stability of oil expelled from the roasted
      perilla seeds. The roasting times were established differently at each roasting
      temperature of 180, 200, and 220  degrees C. Trans fatty acids in perilla oil
      were detected, and the level detected increased as the roasting time increased.
      Moreover, the roasting of perilla seed led to an increase of 4 tocopherols, alpha
      , beta-, gamma-, and delta-tocopherol, as well as phosphorus in the oil. The
      oxidative stability of the oils obtained after roasting increased during 60 d of
      storage at 60  degrees C. The rate of decrease of tocopherol in the oil from
      unroasted perilla seed was faster than that of the tocopherol in the oils from
      roasted perilla seeds during storage.

PMID- 23140340
TI  - Formation of P-C bond through reductive coupling between bridging phosphido and
      benzoquinolinate groups. Isolation of complexes of the Pt(II)/Pt(IV)/Pt(II)
      sequence.
AB  - The rational synthesis of dinuclear asymmetric phosphanido derivatives of
      palladium and platinum(II), [NBu(4)][(R(F))(2)M(MU-PPh(2))(2)M'(kappa(2),N,C
      C(13)H(8)N)] (R(F) = C(6)F(5); M = M' = Pt, 1; M = Pt, M' = Pd, 2; M = Pd, M' =
      Pt, 3; M = M' = Pd, 4), is described. Addition of I(2) to 1-4 gives complexes
      [(R(F))(2)M(II)(MU-PPh(2))(MU-I)Pd(II){PPh(2)(C(13)H(8)N)}] (M = M' = Pt, 6; M =
      Pt, M' = Pd, 7; M = M' = Pd, 8; M = Pd, M' = Pt 10) which contain the
      aminophosphane PPh(2)(C(13)H(8)N) ligand formed through a Ph(2)P/C^N reductive
      coupling on the mixed valence M(II)-M'(IV) [NBu(4)][(R(F))(2)M(II)(MU
      PPh(2))(2)M'(IV)(kappa(2),N,C- C(13)H(8)N)I(2)] complexes, which were identified
      for M(II) = Pd, M'(IV) = Pt (9), and isolated for M(II) = Pt, M'(IV) = Pt (5).
      Complex 5 showed an unusual dynamic behavior consisting in the exchange of two
      phenyl groups bonded to different P atoms, as well as a "through space" spin-spin
      coupling between ortho-F atoms of the pentafluorophenyl rings.

PMID- 23140341
TI  - Using administrative health data to describe colorectal and lung cancer care in
      New South Wales, Australia: a validation study.
AB  - BACKGROUND: Monitoring treatment patterns is crucial to improving cancer patient
      care. Our aim was to determine the accuracy of linked routinely collected
      administrative health data for monitoring colorectal and lung cancer care in New
      South Wales (NSW), Australia. METHODS: Colorectal and lung cancer cases diagnosed
      in NSW between 2000 and 2002 were identified from the NSW Central Cancer Registry
      (CCR) and linked to their hospital discharge records in the NSW Admitted Patient
      Data Collection (APDC). These records were then linked to data from two relevant
      population-based patterns of care surveys. The main outcome measures were the
      sensitivity and specificity of data from the CCR and APDC for disease staging,
      investigative procedures, curative surgery, chemotherapy, radiotherapy, and
      selected comorbidities. RESULTS: Data for 2917 colorectal and 1580 lung cancer
      cases were analysed. Unknown disease stage was more common for lung cancer in the
      administrative data (18%) than in the survey (2%). Colonoscopies were captured
      reasonably accurately in the administrative data compared with the surveys (82%
      and 79% respectively; 91% sensitivity, 53% specificity) but all other colorectal
      or lung cancer diagnostic procedures were under-enumerated. Ninety-one percent of
      colorectal cancer cases had potentially curative surgery recorded in the
      administrative data compared to 95% in the survey (96% sensitivity, 92%
      specificity), with similar accuracy for lung cancer (16% and 17%; 92%
      sensitivity, 99% specificity). Chemotherapy (~40% sensitivity) and radiotherapy
      (sensitivity<=30%) were vastly under-enumerated in the administrative data. The
      only comorbidity that was recorded reasonably accurately in the administrative
      data was diabetes. CONCLUSIONS: Linked routinely collected administrative health
      data provided reasonably accurate information on potentially curative surgical
      treatment, colonoscopies and comorbidities such as diabetes. Other diagnostic
      procedures, comorbidities, chemotherapy and radiotherapy were not well enumerated
      in the administrative data. Other sources of data will be required to
      comprehensively monitor the primary management of cancer patients.

PMID- 23140342
TI  - Fatty acid transporters involved in the palmitate and oleate induced insulin
      resistance in primary rat hepatocytes.
AB  - AIMS: To determine the presence and possible involvement of FAT/CD36, FABPpm and
      FATP-2, transporters in (i) fatty acids movement across plasma membrane and (ii)
      an induction of insulin resistance by palmitic (PA) and oleic (OA) fatty acids in
      primary hepatocytes. METHODS: Primary hepatocytes were treated with either PA and
      OA or combination of activators (AICAR, Insulin) or inhibitors (SSO, phloretin)
      of FA transport. Expression of FA and glucose transporters as well as insulin
      signalling proteins was determined using Western blot analyses. Palmitate and
      glucose transport was measured using radioactive isotopes. Intracellular lipid
      content [ceramide, diacylglycerols (DG) and triacylglycerols] and FA composition
      were estimated by GLC. RESULTS: In primary hepatocytes, adding phloretin
      diminished insulin, and AICAR stimulated palmitate transport. Both PA and OA
      fatty acids induced the protein expression of FAT/CD36 and FATP-2 with
      concomitant: (i) reduction in GLUT-2 protein content, (ii) inhibition of insulin
      stimulated glucose uptake, (iii) reduction in insulin-stimulated activation of
      AKT and GSK, (iv) accumulation of either DG (PA and OA) or ceramide (only PA).
      CONCLUSIONS: FA transport into hepatocytes is, at least in part, protein-mediated
      process, and both PA and OA induce the protein expression of FAT/CD36 and FATP-2.
      Both saturated (PA) and unsaturated (OA) fatty acids induce insulin resistance in
      primary hepatocytes, associated with the accumulation of DG and/or ceramide.

PMID- 23140343
TI  - A systematic review of the relationship between severe maternal morbidity and
      post-traumatic stress disorder.
AB  - BACKGROUND: The incidence of severe maternal morbidity is increasing in high
      income countries as a consequence, in part, of increased obstetric intervention
      and increasingly complex medical needs of women who become pregnant. Access to
      emergency obstetric care means that for the majority of women in these countries,
      an experience of severe maternal morbidity is unlikely to result in loss of life.
      However, little is known about the subsequent impact on postnatal psychological
      health resulting in an evidence gap to support provision of appropriate care for
      these women. There has recently been increasing recognition that childbirth can
      be a cause of post-traumatic stress disorder (PTSD). The combination of
      experiencing a life-threatening complication and its management may culminate in
      psychological trauma. This systematic review examined the association between
      women's experience of severe maternal morbidity during labour, at the time of
      giving birth or within the first week following birth, and PTSD and its symptoms.
      METHODS: Relevant literature was identified through multiple databases, including
      MEDLINE, PsycINFO, EMBASE, CINAHL, British Nursing Index, Web of Science,
      Cochrane library and the British Library, using predetermined search strategies.
      The search terms included "post-traumatic stress disorder", "PTSD", "stress
      disorders, post-traumatic", "maternal morbidity", "pregnancy complications"
      "puerperal disorders", "obstetric labo(u)r complication", "postpartum
      h(a)emorrhage", "eclampsia". Studies identified were categorised according to pre
      defined inclusion and exclusion criteria. The quality of included studies was
      assessed using the relevant CASP appraisal tools. RESULTS: Eleven primary studies
      met review criteria. Evidence of a relationship between severe maternal morbidity
      and PTSD/PTSD symptoms was inconsistent and findings varied between studies.
      Nevertheless, there is some evidence that severe pre-eclampsia is a risk factor
      for PTSD and its symptoms, an association possibly mediated by other factors such
      as fetal/neonatal condition. CONCLUSIONS: Despite the absence of robust evidence
      regarding the relationship between severe maternal morbidity and PTSD/PTSD
      symptoms, it is crucially important that clinicians and policy makers are aware
      of a potential higher risk of PTSD among women who experience severe morbidity.
      Further studies are now needed to confirm this risk as well as to understand
      underlying mechanisms in order to minimise the longer term psychiatric impact of
      severe maternal morbidity.

PMID- 23140344
TI  - Electrophysiology in China: a special supplement. Introduction.

PMID- 23140345
TI  - Another step forward: Journal of Cardiovascular Electrophysiology special issue
      for electrophysiology research from China.

PMID- 23140346
TI  - Atrial electrical and structural remodeling: implications for racial differences
      in atrial fibrillation.
AB  - Racial Disparity in AF Electrophysiology. Racial differences in prevalence and
      incidence rates of atrial fibrillation (AF) are known to exist even after
      accounting for ascertainment bias, as well as differences in the prevalence of
      known risk factors. Thus, a different susceptibility to traditional risk factors
      in different ethnic groups that lead to AF clearly exists. Initiation and
      maintenance of AF are dependent on triggers, autonomic influence and atrial
      substrate, and progression to persistent AF occurs by electromechanical
      remodeling. Genetic differences among the racial group contribute to such
      differences. This article reviews the electrophysiologic mechanisms for AF,
      evidence for racial differences in susceptibility to AF, and suggests possible
      electromechanical reasons for the susceptibility.

PMID- 23140347
TI  - Preventive effectiveness of implantable cardioverter defibrillator in reducing
      sudden cardiac death in the Chinese population: a multicenter trial of ICD
      therapy versus non-ICD therapy.
AB  - Preventive Effectiveness of Implantable Cardioverter. INTRODUCTION: This
      prospective and multicenter trial of the implantable cardioverter-defibrillator
      (ICD) aimed to evaluate the mortality rate (including sudden cardiac death [SCD])
      and the efficacy of ICD in Chinese patients with high risk of sudden death.
      METHODS AND RESULTS: This trial was conducted in 31 centers in China. We enrolled
      497 patients who fulfilled Class I indication for ICD (2002 ACC/AHA/NASPE
      guideline). All patients were followed-up at 3, 6, and 12 months. Clinical
      characteristics and echocardiographic parameters were collected at baseline and
      follow-up; Kaplan-Meier survival analysis was performed. Among 497 enrolled
      patients with Class I indication of ICD therapy, 112 (22.5%) agreed to and
      received ICD implantation (ICD group). The remaining 385 patients who were not
      available for ICD therapy were designated as the non-ICD group. During a mean
      follow-up of 11 +/- 3 months, there were a total of 38 deaths, 2 in the ICD group
      with a mortality of 1.8% and 36 in the non-ICD group, with a mortality of 9.4%
      and 26 due to SCD. The overall survival rate was 93% at 3 months of follow-up,
      91% at 6 months, and 89% at 12 months, with an incidence of SCD of 5%, 7%, and 8%
      at 3, 6, and 12 months, respectively. CONCLUSIONS: In patients with Class I
      indication of ICD implantation, the total mortality and incidence of SCD were
      high. ICD therapy can effectively reduce the mortality in such patients.

PMID- 23140349
TI  - Pressure-tuning infrared and Raman microscopy study of the DNA bases: adenine,
      guanine, cytosine, and thymine.
AB  - Diamond-anvil cell, pressure-tuning infrared (IR), and Raman microspectroscopic
      measurements have been undertaken to examine the effects of high pressures up to
      about 45 kbar on the vibrational spectra of the four DNA bases, adenine,
      cytosine, guanine, and thymine. Small structural changes were evident for all the
      four bases, viz., for adenine and cytosine at 28-31 kbar; for guanine at 16-19
      kbar; and for thymine at 25-26 kbar. These changes are most likely associated
      with alterations in the intermolecular hydrogen-bonding interactions. The
      pressure dependences of the main peaks observed in the IR spectra of the two
      phases of guanine lie in the -0.07-0.66 (low-pressure phase) and 0.06-0.91 (high
      pressure phase) cm-1/kbar ranges. Also, in the Raman spectra of this nucleoside
      base, the dnu/dP values range from -0.07-0.31 (low-pressure phase) to 0.08-0.50
      (high-pressure phase) cm-1/kbar. Similar ranges of dnu/dP values were obtained
      for the other three nucleoside bases.

PMID- 23140348
TI  - Management by the intensivist of gastrointestinal bleeding in adults and
      children.
AB  - Intensivists are regularly confronted with the question of gastrointestinal
      bleeding. To date, the latest international recommendations regarding prevention
      and treatment for gastrointestinal bleeding lack a specific approach to the
      critically ill patients. We present recommendations for management by the
      intensivist of gastrointestinal bleeding in adults and children, developed with
      the GRADE system by an experts group of the French-Language Society of Intensive
      Care (Societe de Reanimation de Langue Francaise (SRLF), with the participation
      of the French Language Group of Paediatric Intensive Care and Emergencies
      (GFRUP), the French Society of Emergency Medicine (SFMU), the French Society of
      Gastroenterology (SNFGE), and the French Society of Digestive Endoscopy (SFED).
      The recommendations cover five fields of application: management of
      gastrointestinal bleeding before endoscopic diagnosis, treatment of upper
      gastrointestinal bleeding unrelated to portal hypertension, treatment of upper
      gastrointestinal bleeding related to portal hypertension, management of presumed
      lower gastrointestinal bleeding, and prevention of upper gastrointestinal
      bleeding in intensive care.

PMID- 23140350
TI  - PanelComposer: a web-based panel construction tool for multivariate analysis of
      disease biomarker candidates.
AB  - Measuring and evaluating diagnostic efficiency is important in biomarker
      discovery and validation. The receiver operating characteristic (ROC) curve is a
      graphical plot for assessing the performance of a classifier or predictor that
      can be used to test the sensitivity and specificity of diagnostic biomarkers. In
      this study, we describe PanelComposer, a Web-based software tool that uses
      statistical results from proteomic expression data and validates biomarker
      candidates based on ROC curves and the area under the ROC curve (AUC) values
      using a logistic regression model and provides an ordered list that includes ROC
      graphs and AUC values for proteins (individually or in combination). This tool
      allows users to easily compare and assess the effectiveness and diagnostic
      efficiency of single or multiprotein biomarker candidates. PanelComposer is
      available publicly at  http://panelcomposer.proteomix.org/  and is compatible
      with major Web browsers.

PMID- 23140351
TI  - Marine natural products and related compounds as anticancer agents: an overview
      of their clinical status.
AB  - Marine ecosystems constitute a huge reservoir of biologically active secondary
      metabolites. Consequently during the last past few decades, several marine
      derived molecules have been approved for anticancer treatment or are under
      clinical trials. This review reports the present state of the art of the sixteen
      molecules approved or currently on the clinical pipeline for anticancer
      chemotherapy. The molecules are classified according to their current status in
      the phase (approved / phase IV / phase III / phase II / phase I) and data are
      updated to April 2012.

PMID- 23140352
TI  - The effects of beta-glucans on cancer metastasis.
AB  - Beta-glucans (beta-glucans), naturally occurring polysaccharides, are present as
      constituents of the cell wall of cereal grains, mushrooms, algae, or microbes
      including bacteria, fungi, and yeast. Since Pillemer et al. first prepared and
      investigated zymosan in the 1940s and others followed with the investigation of
      beta-glucans in the 1960s and 1970s, researchers have well established the
      significant role of beta-glucans on the immune system relative to cancer
      treatment, infection immunity, and restoration of damaged bone marrow. However,
      information on their biological role in anti-metastatic activity remains limited.
      As an immunomodulating agent, beta-glucan acts through the activation of innate
      immune cells such as macrophages, dendritic cells, granulocytes, and natural
      killer cells. This activation triggers the responses of adaptive immune cells
      such as CD4(+) or CD8(+) T cells and B cells, resulting in the inhibition of
      tumor growth and metastasis. Reports have shown that beta-glucans exert multiple
      effects on cancer cells and cancer prevention. However the mechanisms of their
      actions appear complex due to differences in source, chemical structure,
      insufficiently defined preparation, and molecular weight, hence the inconsistent
      and often contradictory results obtained. This review is focused on the potential
      of beta-glucans as anti-metastatic agents and the known mechanisms underlying
      their biological effects.

PMID- 23140353
TI  - beta-Glucans and their applications in cancer therapy: focus on human studies.
AB  - beta-glucans belong to a group of polysaccharides located in the cell wall of
      bacteria, fungi including mushrooms, as well as cereals such as barley and oats.
      All beta-glucans are glucose polymers linked together by a (beta 1-3) linear beta
      glycosidic chain core and they differ by their length and branching structures.
      They are considered biological response modifiers with immunomodulatory and
      health beneficial effects including anticancer properties. Few studies using
      purified beta- glucans were performed, but their anticancer potential was
      demonstrated mainly through studies using extracts from mushrooms, yeast or other
      sources which contain beta-glucan as a key component. Their anticancer effects
      were demonstrated mainly in in vitro and in vivo experimental systems but fewer
      studies from human populations are available. beta-glucans have been used as
      adjuvant therapy in clinical trials, mainly in the Far East, with a positive
      effect on patients'survival and quality of life. The mechanism of action is
      suggested to be through its stimulation of the immune system. This review focuses
      on human studies; clinical trials and epidemiological data assessing the efficacy
      and safety of mushroom-derived beta- glucans in cancer treatment and prevention.
      The potential direct effects of beta-glucans on cancer cells are also described.

PMID- 23140354
TI  - Synthetic oligosacharides--clinical application in cancer therapy.
AB  - It is well established that glucans enhance the efficacy of anti-cancer and anti
      infection immunotherapy, both in clinical and experimental conditions. However,
      the considerable variations among batches of natural glucan in molecular weight,
      branching frequency, as well as linkage to chitins and mannoproteins, make the
      clinical applications of natural glucan questionable. The future might be in the
      use of small synthetic oligosaccharides prepared on the basis of natural glucans.
      Some of these non natural oligosaccharides showed biological activities such as
      stimulation of phagocytosis, modulation of gene expression and anti-cancer
      activity, which were superior to natural glucans. The recent studies strongly
      suggest the possibility of small chemical changes in the structure of these
      oligoglucans oriented towards their improved biological activities. This review
      highlights recent achievements in the immunological effects of synthetic, glucan
      based oligosaccharides.

PMID- 23140355
TI  - Erlotinib and gefitinib for elderly patients with advanced non-small-cell lung
      cancer.
AB  - Erlotinib and gefitinib are tyrosine kinase inhibitors (TKI) associated with the
      EGFR, which is involved in cell proliferation, growth, migration, invasion and
      survival, and has been found to be overexpressed in non-small-cell lung cancer.
      Erlotinib was the first target agent approved for the treatment of NSCLC in
      second- and third line, in patients unselected for EGFR mutations; gefitinib was
      the first EGFR tyrosine kinase inhibitor approved for the treatment of NSCLC in
      all lines of setting in patients harbouring EGFR mutations. In elderly patients,
      with a poor prognosis, and different co-morbidities, erlotinib and gefitinib
      could be considered as valid therapeutic options. This paper reviews the role of
      both drugs, in the management of elderly patients affected by advanced NSCLC
      based on an update analysis of randomised and non-randomised clinical trials. 

PMID- 23140356
TI  - Extracting structural information from the polarization dependence of one- and
      two-dimensional sum frequency generation spectra.
AB  - We present ways in which pulse sequences and polarizations can be used to extract
      structural information from one- and two-dimensional vibrational sum frequency
      generation (2D SFG) spectra. We derive analytic expressions for the polarization
      dependence of systems containing coupled vibrational modes, and we present
      simulated spectra to identify the features of different molecular geometries. We
      discuss several useful polarization combinations for suppressing strong diagonal
      peaks and emphasizing weaker cross-peaks. We investigate unique capabilities of
      2D SFG spectra for obtaining structural information about SFG-inactive modes and
      for identifying coupled achiral chromophores. This work builds on techniques that
      have been developed for extracting structural information from 2D IR spectra.
      This paper discusses how to utilize these concepts in 2D SFG experiments to probe
      multioscillator systems at interfaces. The sample code for calculating
      polarization dependence of 1D and 2D SFG spectra is provided in the Supporting
      Information . 

PMID- 23140357
TI  - Investigation of strategies for the introduction and transportation of
      replacement gilts on southern Ontario sow farms.
AB  - BACKGROUND: Porcine reproductive and respiratory syndrome (PRRS) is of major
      concern to the swine industry; infection with the virus can lead to production
      losses, morbidity, and mortality within swine operations. Biosecurity practices
      related to the management of replacement animals are important for the prevention
      and control of the PRRS virus, as well as other diseases. The objectives of this
      study were: (i) to describe individual biosecurity practices related to the
      introduction and transportation of replacement gilts on southern Ontario sow
      farms, and (ii) to understand patterns in the implementation of these practices.
      The second objective was accomplished using multiple correspondence analysis
      (MCA), which allows visualization of the relationships between individual
      practices and provides information about which practices frequently occur
      together, and which practices rarely occur together. These patterns constitute
      strategies for the implementation of biosecurity practices related to the
      introduction and transportation of replacement gilts. Data were collected using
      version 2 of the Production Animal Disease Risk Assessment Program's survey for
      the breeding herd. Two subsets of variables were retained for analysis; one
      subset pertained to how replacements were managed upon arrival to the farm, and
      the other pertained to the transportation of genetic animals. RESULTS: For both
      subsets of variables, the results of the MCA procedure were similar; in both
      solutions the 1st dimension separated herds that were closed with respect to
      replacement animals from herds that were open, and the 2nd dimension described
      how open herds managed replacements. The most interesting finding of this study
      was that, in some cases where a risky practice was being implemented, it was
      closely associated with other biosecurity practices that may mitigate that risk.
      CONCLUSIONS: The findings from this approach suggest that one cannot always
      examine biosecurity on a variable-by-variable basis. Even if a practice that is
      generally considered high-risk is being implemented, it may be balanced by other
      practices that mitigate that risk. Thus, the overall biosecurity strategy on a
      farm must be considered instead of only examining the implementation of
      individual practices.

PMID- 23140358
TI  - Synthesis and biological evaluation (in vitro and in vivo) of cyclic arginine
      glycine-aspartate (RGD) peptidomimetic-paclitaxel conjugates targeting integrin
      alphaVbeta3.
AB  - A small library of integrin ligand-paclitaxel conjugates 10-13 was synthesized
      with the aim of using the tumor-homing cyclo[DKP-RGD] peptidomimetics for site
      directed delivery of the cytotoxic drug. All the paclitaxel-RGD constructs 10-13
      inhibited biotinylated vitronectin binding to the purified alphaVbeta3 integrin
      receptor at low nanomolar concentration and showed in vitro cytotoxic activity
      against a panel of human tumor cell lines similar to that of paclitaxel. Among
      the cell lines, the cisplatin-resistant IGROV-1/Pt1 cells expressed high levels
      of integrin alphaVbeta3, making them attractive to be tested in in vivo models.
      cyclo[DKP-f3-RGD]-PTX 11 displayed sufficient stability in physiological solution
      and in both human and murine plasma to be a good candidate for in vivo testing.
      In tumor-targeting experiments against the IGROV-1/Pt1 human ovarian carcinoma
      xenotransplanted in nude mice, compound 11 exhibited a superior activity compared
      with paclitaxel, despite the lower (about half) molar dosage used.

PMID- 23140359
TI  - Breathing training characterization by thermal imaging: a case study.
AB  - Specific respiratory muscle training improves athletes' performance particularly
      at high intensities. This work aims to study the usability of infrared
      thermography to evaluate two types of breathing, thoracic and diaphragmatic, on
      the cartographies of the cutaneous temperature of the trunk. IR thermography is a
      non-invasive technique that visually represents the whole process during and
      after training. A well trained subject in both respirations performed the
      exercise with SpiroTiger(r) for 5 minutes, followed by 5 minutes of recovery. Ten
      Regions of Interest on the subject skin were selected following anatomical and
      functional correspondence with the muscles involved in breathing. In order to
      check functional behaviour of respiratory muscles, we calculated the correlation
      among thermal data of all the ROI. Global temperature of body trunk showed a
      general decrease of few degrees during both kinds of the training but thermal
      imaging documented also thermal spots of increasing temperature in pectoral areas
      due to the superficial vasocirculation in thoracic breathing. The results
      indicate that thermal imaging can be used for quantitative evaluation of the
      cutaneous temperature in various trunk zones characterized by thoracic and
      diaphragmatic breathing. This work can be considered a preliminary study to the
      development of future statistical study.

PMID- 23140360
TI  - Fibrillar self-organization of a line-active partially fluorinated thiol within
      binary self-assembled monolayers.
AB  - Self-assembled monolayers (SAMs) were prepared from a novel two-tailed partially
      fluorinated thiol (F8C11/C16), possessing one hydrocarbon chain and one chain
      with an extended fluorinated segment, and from mixtures of F8C11/C16 and
      hexadecanethiol (C16) on gold, with the expectation that the internal chemical
      dissimilarity and wedge-like shape of F8C11/C16 would lead to unique self
      organizational motifs. The SAMs were systematically characterized using
      ellipsometry, atomic force microscopy (AFM), X-ray photoelectron spectroscopy
      (XPS), contact angle goniometry, and polarization modulation infrared reflection
      absorption spectroscopy (PM-IRRAS). Based on this characterization, the one
      component F8C11/C16 SAMs exhibited relatively poor molecular organization
      compared to traditional alkanethiols, forming low coverage monolayers with
      significant molecular disorder. However, the series of mixed SAMs formed from
      F8C11 and F8C11/C16 were anomalously well ordered as indicated by film thickness,
      surface coverage, and the frequencies of characteristic vibrational modes. AFM
      images of these mixed SAMs exhibited nanoscale fibrillar structures in a birds
      nest morphology, suggesting that in the presence of a C16 matrix, the F8C11/C16
      component organized into the two-dimensional analogue of discrete bilayers.
      Control experiments involving mixed SAMs comprised of F8C11/C16 and a single
      tailed partially fluorinated thiol (F8C11) or C16 and F8C11 exhibited no
      appreciable indication of interesting self-organization beyond an evenly
      dispersed mixing of the thiolates or phase separation, respectively.

PMID- 23140361
TI  - Look-ahead fixations in curve driving.
AB  - Two functionally distinct types of fixation, guiding fixations and look-ahead
      fixations, have been identified in naturalistic tasks based on their temporal
      relationship to the task execution. In car driving, steering through a curve is
      guided by fixations toward a region located 1-2 s in the future, but drivers also
      make fixations further along the road. We recorded drivers' eye movements while
      they drove an instrumented vehicle on curved rural roads and developed a method
      to quantify lead time and distance of look-ahead fixations. We also investigated
      the effect of cognitive load on look-ahead fixations. The look-ahead fixations
      appear to have a pattern which is connected to the sequential structure of a
      curve. This suggests that they have a role both in advance planning of the
      driving line and in the anticipation of oncoming vehicles. Cognitive load led to
      a shorter look-ahead lead time and distance. PRACTITIONER SUMMARY: We developed a
      method to quantify lead time and distance of look-ahead fixations in curve
      driving from on-road eye movement data. The results are relevant for driver
      modelling and development of anticipation training programmes for novice drivers.

PMID- 23140362
TI  - Occurrence of biogenic amines in Miso, Japanese traditional fermented soybean
      paste.
AB  - The objective of this study was to analyze overall contents of biogenic amines in
      Miso and thereby evaluate the safety of the food. Through HPLC analysis of 22
      different Miso products, it was found that most samples had low biogenic amine
      contents. However, some samples contained both histamine and tyramine close to
      hazardous levels of the amines, which indicate that the amounts of biogenic
      amines in Miso are not completely within the safe level for human health.
      Meanwhile, the biogenic amine contents showed no clear relationship with
      physicochemical parameters, whereas they revealed a good relationship with the
      ratio of soybean to other grains used in raw material. Thus, it turned out that
      biogenic amine contents in Miso are primarily affected by the ratio of raw
      ingredients, especially soybeans. The aerobic plate counts of Miso samples ranged
      from 3 to 8 Log CFU/g, and all the strains isolated from Miso samples were found
      to produce biogenic amines. Most strains were identified to be Bacillus subtilis,
      often regarded as the predominant contaminant bacteria in Miso, and highly
      capable of producing tyramine and spermine. Taken together, therefore, this study
      suggests that variability of biogenic amine contents in Miso are primarily
      attributed to the ratio of raw ingredients in the food that affects the relative
      contribution level of bacterial contaminants to the contents.

PMID- 23140363
TI  - Photoinduced reactions between Pb3O4 and organic dyes in aqueous solution under
      visible light.
AB  - Pb(3)O(4) could react with organic dyes in aqueous solution under visible light
      irradiation, in which Pb(3)O(4) was transformed into Pb(3)(CO(3))(2)(OH)(2) along
      with oxidation of the organic dyes. Cu(2+) has considerable effect on the
      reaction. In the presence of Cu(2+), MO (20 ppm) and RhB (10(-5) mol L(-1)) were
      completely degraded under visible light within 6 and 20 min, respectively, while
      both Pb(3)O(4) and Cu(2+) keep almost stable during photodegradation. The
      mechanisms of the reactions with and without Cu(2+) ions were studied. The
      photochemical system of Pb(3)O(4) cooperating with Cu(2+) ions is probably used
      for the treatment of organic pollutants in water under visible light.

PMID- 23140364
TI  - In vitro monitoring of the dynamic elasticity changes during radiofrequency
      ablation with acoustic radiation force impulse imaging.

PMID- 23140365
TI  - MALVAC 2012 scientific forum: accelerating development of second-generation
      malaria vaccines.
AB  - The World Health Organization (WHO) convened a malaria vaccines committee
      (MALVAC) scientific forum from 20 to 21 February 2012 in Geneva, Switzerland, to
      review the global malaria vaccine portfolio, to gain consensus on approaches to
      accelerate second-generation malaria vaccine development, and to discuss the need
      to update the vision and strategic goal of the Malaria Vaccine Technology
      Roadmap. This article summarizes the forum, which included reviews of leading
      Plasmodium falciparum vaccine candidates for pre-erythrocytic vaccines, blood
      stage vaccines, and transmission-blocking vaccines. Other major topics included
      vaccine candidates against Plasmodium vivax, clinical trial site capacity
      development in Africa, trial design considerations for a second-generation
      malaria vaccine, adjuvant selection, and regulatory oversight functions including
      vaccine licensure.

PMID- 23140367
TI  - Mammalian phospholipase C.
AB  - Phospholipase C (PLC) converts phosphatidylinositol 4,5-bisphosphate (PIP(2)) to
      inositol 1,4,5-trisphosphate (IP(3)) and diacylglycerol (DAG). DAG and IP(3) each
      control diverse cellular processes and are also substrates for synthesis of other
      important signaling molecules. PLC is thus central to many important interlocking
      regulatory networks. Mammals express six families of PLCs, each with both unique
      and overlapping controls over expression and subcellular distribution. Each PLC
      also responds acutely to its own spectrum of activators that includes
      heterotrimeric G protein subunits, protein tyrosine kinases, small G proteins,
      Ca(2+), and phospholipids. Mammalian PLCs are autoinhibited by a region in the
      catalytic TIM barrel domain that is the target of much of their acute regulation.
      In combination, the PLCs act as a signaling nexus that integrates numerous
      signaling inputs, critically governs PIP(2) levels, and regulates production of
      important second messengers to determine cell behavior over the millisecond to
      hour timescale.

PMID- 23140366
TI  - Aging, cellular senescence, and cancer.
AB  - For most species, aging promotes a host of degenerative pathologies that are
      characterized by debilitating losses of tissue or cellular function. However,
      especially among vertebrates, aging also promotes hyperplastic pathologies, the
      most deadly of which is cancer. In contrast to the loss of function that
      characterizes degenerating cells and tissues, malignant (cancerous) cells must
      acquire new (albeit aberrant) functions that allow them to develop into a lethal
      tumor. This review discusses the idea that, despite seemingly opposite
      characteristics, the degenerative and hyperplastic pathologies of aging are at
      least partly linked by a common biological phenomenon: a cellular stress response
      known as cellular senescence. The senescence response is widely recognized as a
      potent tumor suppressive mechanism. However, recent evidence strengthens the idea
      that it also drives both degenerative and hyperplastic pathologies, most likely
      by promoting chronic inflammation. Thus, the senescence response may be the
      result of antagonistically pleiotropic gene action.

PMID- 23140369
TI  - Medicinal and aromatic plants legislation in the European Union, Italy and
      several of its regions.
AB  - This study analysed particular regulations on the cultivation and collection of
      medicinal and aromatic plants (MAPs) in the European Union, Italy and several of
      its regions. Piedmont and Valle d'Aosta (Northwest), Tuscany (Central) and Sicily
      (South). The analysis should emphasise to private and/or public institutions the
      information to further develop and improve MAP cultivation, both in the
      considered context and beyond it.

PMID- 23140368
TI  - Claudins and the kidney.
AB  - Claudins are tight junction membrane proteins that regulate paracellular
      permeability of renal epithelia to small ions, solutes, and water. Claudins
      interact within the cell membrane and between neighboring cells to form tight
      junction strands and constitute both the paracellular barrier and the pore. The
      first extracellular domain of claudins is thought to be the pore-lining domain
      and contains the determinants of charge selectivity. Multiple claudins are
      expressed in different nephron segments; such differential expression likely
      determines the permeability properties of each segment. Recent evidence has
      identified claudin-2 as constituting the cation-reabsorptive pathway in the
      proximal tubule; claudin-14, -16, and -19 as forming a complex that regulates
      calcium transport in the thick ascending limb of the loop of Henle; and claudin
      4, -7, and -8 as determinants of collecting duct chloride permeability. Mutations
      in claudin-16 and -19 cause familial hypercalciuric hypomagnesemia with
      nephrocalcinosis. The roles of other claudins in kidney diseases remain to be
      fully elucidated.

PMID- 23140370
TI  - The effects of police duty belt and seat design changes on lumbar spine posture,
      driver contact pressure and discomfort.
AB  - Police officers spend large amounts of time performing duties within a police
      cruiser and report a high prevalence of musculoskeletal problems. This study
      evaluated the effects of driver seat and duty belt design on posture, pressure
      and discomfort. Ten male and 10 female university students attended two sessions
      involving simulated driving in a standard police seat (CV) and an active lumbar
      support (ALS) seat. Participants wore a full duty belt (FDB) or reduced duty belt
      (RDB) in each seat. Lumbar postures, driver-seat and driver-duty belt pressures
      and perceived discomfort were measured. Gender * Seat interactions were found for
      pelvic (p = 0.0001) and lumbar postures (p = 0.003). Females had more lumbar
      flexion than males and were more extended in the ALS seat (-9.8 +/- 11.3 degrees
      ) than CV seat (-19.8 +/- 9.6 degrees ). The FDB had greater seat pressure than
      the RDB (p < 0.0001), which corresponded to increased pelvis discomfort. This
      study supports the use of an ALS seat and RDB to reduce injury risk associated
      with prolonged sitting in police officers. PRACTITIONER SUMMARY: Police officers
      report a high prevalence of musculoskeletal problems to the lower back,
      associated with prolonged driving and further investigation is needed to reduce
      injury risk. This simulated driving study investigated seat and duty belt
      configuration on biomechanical measures and discomfort. Seat design had the
      greatest impact, regardless of gender and males benefited more from a reduced
      belt configuration.

PMID- 23140371
TI  - A musculoperiosteal flap cochlear implant device fixation technique: our
      experience in one hundred and seventy nine patients.

PMID- 23140372
TI  - Quantitative hormone therapy follow-up in an ER+/ERalphaKD mouse tumor model
      using FDG and [11C]-methionine PET imaging.
AB  - BACKGROUND: The estrogen receptor alpha (ERalpha) is known to play an important
      role in the modulation of tumor response to hormone therapy. In this work, the
      effect of different hormone therapies on tumors having different ERalpha
      expression levels was followed up in vivo in a mouse model by PET imaging using 2
      deoxy-2-[18F]fluoro-d-glucose (FDG) and [11C]-methionine ([11C]-MET). A new model
      of MC7-L1 ERalpha-knockdown (ERalphaKD) tumor cell lines was designed as a
      negative estrogen receptor control to follow up the effects of changes in ERalpha
      expression on the early metabolic tumor response to different hormone therapies.
      METHODS: MC7-L1 (ER+) and MC7-L1 ERalpha-knockdown cell lines were implanted
      subcutaneously in Balb/c mice and allowed to grow up to 4 mm in diameter. Animals
      were separated into 4 groups (n = 4 or 5) and treated with a pure antiestrogen
      (fulvestrant), an aromatase inhibitor (letrozole), a selective estrogen receptor
      modulator (tamoxifen), or not treated (control). Tumor metabolic activity was
      assessed by PET imaging with FDG and [11C]-MET at days 0 (before treatment), 7,
      and 14 after the treatment. Tumor uptake of each radiotracer in %ID/g was
      measured for each tumor at each time point and compared to tumor growth.
      Quantitative PCR (qPCR) was performed to verify the expression of breast cancer
      related genes (ERalpha, ErbB2, progesterone receptor (PR), and BRCA1) in each
      tumor cell lines. RESULTS: While both ER+ and ERalphaKD tumors had similar uptake
      of both radiotracers without treatment, higher uptake values were generally seen
      in ERalphaKD tumors after 7 and 14 days of treatment, indicating that ERalphaKD
      tumors behave in a similar fashion as hormone-unresponsive tumors. Furthermore,
      the ERalpha-specific downregulation induced a slight PR expression decrease and
      overexpression of BRCA1 and ErbB2. CONCLUSION: The results indicate that the
      proposed ER+/ERalphaKD tumor-bearing mouse model is suitable to test pure
      antiestrogen and aromatase inhibitor therapies in vivo in a preclinical setting
      and could help to elucidate the impact of ERalpha levels on tumor response to
      hormone therapy.

PMID- 23140373
TI  - Two years after cancer diagnosis, what is the relationship between health-related
      quality of life, coping strategies and spirituality?
AB  - This study aimed to analyze the relationship between spirituality, coping
      strategies and health-related quality of life (HRQL) among a large representative
      sample of patients two years after cancer diagnosis. Using a cross-sectional
      design, medical and self-reported data were collected by physicians and a patient
      telephone interview, respectively. Among 4270 participants, 54.6% reported that
      spirituality was not a source of comfort at all during the disease, 23.4% stated
      that it was a source of moderate comfort and 22.5% a source of great comfort.
      After adjustment for age, gender, educational level and living in a couple, a
      multivariate analysis showed that a lower mental HRQL score was independently
      associated with finding moderate comfort in spirituality when compared with
      finding no comfort at all. After multiple adjustment, a lower score of physical
      HRQL and a higher score of fighting spirit were independently associated with
      having found great comfort in spirituality when compared with those who found no
      comfort at all. This study aimed to understand the dynamics of religious beliefs
      among cancer patients over the disease duration and to understand how these
      beliefs could be considered and utilized by patients as a source of comfort and
      support. The results highlight not only the role spirituality may play in disease
      management and the extent to which it may be a valuable source of comfort during
      the follow-up of cancer patients, but also its role in the evaluation of the
      different dimensions of HRQL. 

PMID- 23140374
TI  - An automated template-based adaptive threshold approach for measuring ventricular
      volume enlargement in mouse brain MR microscopy.
AB  - Mouse models for human diseases play an important role in developing therapeutic
      measures and understanding disease development and mechanisms. Ventricular
      enlargement is an objective and sensitive biomarker of neuropathological change
      associated with mild cognitive impairment (MCI) and Alzheimer's disease (AD).
      Thus, imaging based volumetric measures of mouse brain ventricle can be used as a
      biomarker for detecting and monitoring pathology. However, till now most mouse
      ventricular segmentation is still based on manual tracing, and current region of
      interests (ROIs) labelling approaches on mouse brain don't work well on small
      brain structure like ventricle. In this paper, an automated template-based method
      was developed to evaluate for the identification of a ventricular ROIs in mouse
      brain imaging studies. Monte Carlo simulation was applied to evaluate the
      efficiency of this approach in detecting computer-simulated ventricle in
      laboratory mice. The method demonstrated a satisfactory performance with
      consistent high correlations between the detected and simulated volume changes.
      This approach can be used to investigate the ventricular volume changing in
      transgenic mice and other putative animal models of AD.

PMID- 23140375
TI  - Direct observation of the spatial distribution of charges on a polypropylene
      fiber via Electrostatic Force Microscopy.
AB  - The spatial distribution of electrical charges along the longitudinal axes of a
      polypropylene electret fiber was determined using Electrostatic Force Microscopy
      (EFM). EFM mapping on highly curved surfaces, such as those of polymeric fibers,
      is a challenging endeavour and most work reported in the scientific literature
      has been limited to single line-scan analysis or flat specimens. Charged
      polymeric fibers, electrets, are extensively used in high performance filtration
      applications and methods to determine the amount and magnitude of the charges on
      these fibers remain elusive. Electrical charge maps of individual fibers were
      obtained by biasing the tip to -10 V and maintaining a constant tip-sample
      distance of 100 nm. Spatially dependant EFM phase and magnitude gradients were
      determined and the developed technique may provide a unique understanding into
      the heterogeneous charge distribution on electrets fibers. Direct mapping of the
      charge distribution in electrets fibers can offer new insights in the development
      of antistatic additives, new means to facilitate electrostatic self-assembly of
      nano-moieties on the surface of fibrous materials and a quantitative metrics
      capable of determining discharge dynamics and predicting the shelf-life of
      filtration media.

PMID- 23140376
TI  - Bilateral prediction and intersection calculation autofocus method for automated
      microscopy.
AB  - In this paper, a bilateral prediction and intersection calculation autofocus
      method for automated microscopy, which obtains the in-focus position by
      calculating the intersection of the predicted left and right focus measure curves
      located respectively in the left and right sides of the peak position of the
      focus measure curve, is proposed and performed. According to the autofocus
      method, the area including the peak position of the focus measure curve and its
      left and right neighbourhoods should be determined firstly, and the left and
      right neighbourhoods are considered as the left and right sampling areas. The
      left and right focus measure curves are predicted by appropriate predicting
      models according to the two sample sequences, which comprise the focus values by
      evaluating the sampled images in the left sampling area and right sampling area,
      respectively and their corresponding sampling positions. The intersection of the
      predicted left and right focus measure curves is calculated and can be considered
      as the in-focus position. The autofocus can be realized by moving the focus plane
      of the microscope to the intersection of the predicted left and right focus
      measure curves. The proposed bilateral prediction and intersection calculation
      autofocus method is experimentally verified in an automated light microscopy for
      implementing microassembly and micromanipulation. The theoretical analyses have
      shown that the proposed bilateral prediction and intersection calculation
      autofocus method can not only effectively avoid the principle error caused by
      assuming the symmetrical focus measure curve in the autofocus methods based on
      curve fitting, but also eliminate the possible waver search near the peak
      position in the modified fast climbing servo method. The experimental results
      have shown that the proposed bilateral prediction and intersection calculation
      autofocus method possesses the merits as follows: (1) the focusing accuracy is
      high and slightly affected by the sampling step size and (2) the focusing speed
      is higher than those of the 7-point hill-climbing search method and the quadratic
      curve fitting method with a determinate focusing accuracy.

PMID- 23140377
TI  - Utilizing confocal microscopy to measure refractive index of articular cartilage.
AB  - This study proposes a method for measuring the refractive index of articular
      cartilage within a thin and small specimen slice. The cartilage specimen, with a
      thickness of about 50 MUm, was put next to a thin film of immersion oil of
      similar thickness. Both the articular cartilage and immersion oil were scanned
      along the depth direction using a confocal microscope. The refractive index
      mismatch between the cartilage and the immersion oil induced a slight axial
      deformation in the confocal images of the cartilage specimen that was accurately
      measured by a subpixel edge-detection-based technique. A theoretical model was
      built to quantify the focal shift of confocal microscopy caused by the refractive
      index mismatch. With the quantitative deformations of cartilage images and the
      quantified function of focal shift, the refractive index of articular cartilage
      was accurately interpolated. At 561 nm, 0.1 MPa and 20  degrees C, the overall
      refractive index of the six cartilage plugs was 1.3975 +/- 0.0156. The overall
      coefficient of variation of all cartilage specimens was 0.68%, which indicated
      the high repeatability of our method. The verification experiments using
      distilled water showed a minimal relative error of 0.02%.

PMID- 23140378
TI  - Three-dimensional reconstructions from optical sections of thick mouse inner ears
      using confocal microscopy.
AB  - Three-dimensional (3D) reconstructions of the vertebrate inner ear have provided
      novel insights into the development of this complex organ. 3D reconstructions
      enable superior analysis of phenotypic differences between wild type and mutant
      ears but can result in laborious work when reconstructed from physically
      sectioned material. Although nondestructive optical sectioning light sheet
      microscopy may ultimately prove the ideal solution, these technologies are not
      yet commercially available, or in many instances are not monetarily feasible.
      Here we introduce a simple technique to image a fluorescently labelled ear at
      different stages throughout development at high resolution enabling 3D
      reconstruction of any component of the inner ear using confocal microscopy. We
      provide a step-by-step manual from tissue preparation to imaging to 3D
      reconstruction and analysis including a rationale and troubleshooting guide at
      each step for researchers with different equipment, protocols, and access to
      resources to successfully incorporate the principles of this method and customize
      them to their laboratory settings.

PMID- 23140380
TI  - O(6)-methylguanine-DNA methyltransferase in equine sarcoids: molecular and
      epigenetic analysis.
AB  - BACKGROUND: Bovine papillomaviruses (BPVs) types 1 and 2 are the only known
      papillomaviruses able to jump the species. In fact, BPVs 1/2 induce neoplasia in
      their natural bovine host but infection is also associated to neoplastic skin
      lesions in equids termed sarcoids. The equine sarcoid is considered to be the
      most common equine cutaneous tumour worldwide for which no effective therapy is
      available. Very little is known about the molecular mechanisms underlying
      tumourigenesis, although genes contributing to sarcoid development have been
      identified. Several studies associate the development of cancer to the loss of
      function of a number of oncosuppressor genes. In this study the putative role of
      O6-methylguanine-DNA methyltrasferase (MGMT) was investigated for sarcoids. The
      expression of the oncosuppressor protein was assessed in normal and sarcoid cells
      and tissues. In addition, the DNA methylation profile was analysed to assess the
      role of epigenetic mechanism in regulation of MGMT expression. RESULTS: A group
      of 15 equine sarcoids and two primary sarcoid cell lines (fibroblasts) were
      analyzed for the expression of MGMT protein by immunohistochemistry,
      immunofluorescence and Western blotting techniques. The sarcoid cell line EqSO4b
      and the tumour samples showed a reduction or absence of MGMT expression. To
      investigate the causes of deregulated MGMT expression, ten samples were analyzed
      for the DNA methylation profile of the CpG island associated to the MGMT
      promoter. The analysis of 73 CpGs encompassing the region of interest showed in 1
      out of 10 (10%) sarcoids a pronouncedly altered methylation profile when compared
      to the control epidermal sample. Similarily the EqSO4b cell line showed an
      altered MGMT methylation pattern in comparison to normal fibroblasts. CONCLUSION:
      As previously demonstrated for the oncosuppressor gene FHIT, analysis of MGMT
      expression in sarcoid tissues and a sarcoid-derived fibroblast cell line further
      suggests that oncosuppressor silencing may be also involved in BPV-induced equine
      tumours. Abnormal DNA methylation seems to be one of the possible molecular
      mechanisms involved in the alteration of MGMT expression. Further studies are
      required to address other basic molecular mechanisms involved in reduced MGMT
      expression. This study underlines the possible role of DNA methylation in
      oncosuppressor inactivation in equine sarcoids.

PMID- 23140381
TI  - Numerical modelling and verification of Polish ventricular assist device.
AB  - The developed multiscale model of blood chamber of POLVAD (Polish ventricular
      assist device) was introduced. The tension test for polymer and digital image
      correlation (DIC) were performed for verification of the strains and
      displacements obtained in the numerical model of POLVAD_EXT. The numerical
      simulations were carried out in conditions given in the experiment to compare the
      results obtained on external surfaces of blood chamber of the POLVAD_EXT. The
      examined polymer applied in the POLVADs is sensitive to changes of temperature
      and this observation is considered in all prepared numerical models. The
      comparison of experimental and numerical results shows acceptable coincidence.
      There are some heterogeneous distributions of strains in experiment with respect
      to analysis of computed parameters. The comparison of two versions of blood
      chambers (POLVAD and POLVAD_EXT) in numerical analysis shows that POLVAD_EXT
      construction is better with respect to analysis of strain and stress. The maximum
      values of computed parameters are located in the regions between connectors on
      the internal surfaces of blood chambers of POLVAD.

PMID- 23140382
TI  - Structural insights into the South African HIV-1 subtype C protease: impact of
      hinge region dynamics and flap flexibility in drug resistance.
AB  - The HIV protease plays a major role in the life cycle of the virus and has long
      been a target in antiviral therapy. Resistance of HIV protease to protease
      inhibitors (PIs) is problematic for the effective treatment of HIV infection. The
      South African HIV-1 subtype C protease (C-SA PR), which contains eight
      polymorphisms relative to the consensus HIV-1 subtype B protease, was expressed
      in Escherichia coli, purified, and crystallized. The crystal structure of the C
      SA PR was resolved at 2.7 A, which is the first crystal structure of a HIV-1
      subtype C protease that predominates in Africa. Structural analyses of the C-SA
      PR in comparison to HIV-1 subtype B proteases indicated that polymorphisms at
      position 36 of the homodimeric HIV-1 protease may impact on the stability of the
      hinge region of the protease, and hence the dynamics of the flap region.
      Molecular dynamics simulations showed that the flap region of the C-SA PR
      displays a wider range of movements over time as compared to the subtype B
      proteases. Reduced stability in the hinge region resulting from the absent E35
      R57 salt bridge in the C-SA PR, most likely contributes to the increased
      flexibility of the flaps which may be associated with reduced susceptibility to
      PIs.

PMID- 23140383
TI  - Synthesis and biological characterization of 3-substituted 1H-indoles as ligands
      of GluN2B-containing N-methyl-D-aspartate receptors. Part 2.
AB  - In the course of the identification of new indole derivatives targeting GluN2B
      subunit-containing N-methyl-D-aspartate (NMDA) receptor, the (N-1H-indol-6
      methanesulfonamide-3-yl)-2-(4-benzylpiperidin-1-yl)ethanone (10b) was identified
      as a potent ligand for this NMDA receptor subunit. It displays very high binding
      affinity (IC50 of 8.9 nmol) for displacement of [3H]ifenprodil, thus showing
      improved potency with respect to the previously reported analogues as confirmed
      by functional assay. This finding was consistent with the docking pose of
      compound 10b within the binding pocket localized in the GluN1-GluN2B subunit
      interface of NMDA receptor tetraheteromeric complex.

PMID- 23140384
TI  - Amino termini of many yeast proteins map to downstream start codons.
AB  - Comprehensive knowledge of proteome complexity is crucial to understanding cell
      function. Amino termini of yeast proteins were identified through peptide mass
      spectrometry on glutaraldehyde-treated cell lysates as well as a parallel
      assessment of publicly deposited spectra. An unexpectedly large fraction of
      detected amino-terminal peptides (35%) mapped to translation initiation at AUG
      codons downstream of the annotated start codon. Many of the implicated genes have
      suboptimal sequence contexts for translation initiation near their annotated AUG,
      and their ribosome profiles show elevated tag densities consistent with
      translation initiation at downstream AUGs as well as their annotated AUGs. These
      data suggest that a significant fraction of the yeast proteome derives from
      initiation at downstream AUGs, increasing significantly the repertoire of encoded
      proteins and their potential functions and cellular localizations.

PMID- 23140385
TI  - Alteration of cholinergic system in keratinocytes cells produces acantholysis: a
      possible use of cholinergic drugs in pemphigus vulgaris.
AB  - Human epidermis shows a non-neuronal cholinergic system including keratinocyte
      (kc) acetylcholine (Ach) axis which is composed by enzymes and two families of
      Ach receptors (muscarinic and nicotinic receptors). The activity of these two
      receptors can regulate the interkeratinocytes and kcs-extracellular matrix
      adhesion modifying the regulation of intercellular adhesion molecules like
      cadherins and integrins. Some authors demonstrate that acantholysis in pemphigus
      depends not only on anti desmogleins antibodies (abs) (mostly IgG) but even on
      other abs directed against kc membrane antigens (e.g. anti Ach receptors Abs). In
      the early phase of pemphigus pathogenesis, anti Ach receptors Abs block Ach
      signaling essential for cell shape and intercellular adhesion and increase the
      phosphorylation of adhesion molecules. Combined with the action of abs
      antidesmogleins, anti Ach receptors Abs cause the acantholytic phenomenon. In
      vitro experiments show that high doses of Ach in acantholytic kcs can rapidly
      reverse this pathologic event. In vivo experiments using neonatal mice model of
      Pemphigus have demonstrated that cholinergic agonists reduce these lesions.
      Therapy with pyridostigmine bromide and Nicotinamide per os or pilocarpine used
      topically, drugs that present cholinomimetic effects, has lead to encouraging
      results in patients affected by Pemphigus disease. Cholinergic agents could have
      a strategic role in the therapy of pemphigus since they could be responsible for
      the early stage of acantholytic diseases.

PMID- 23140386
TI  - An algorithm to measure beat-to-beat cycle lengths for assessment of atrial
      electrogram rate and regularity during atrial fibrillation.
AB  - INTRODUCTION: Experimental models have demonstrated that atrial fibrillation (AF)
      may be due to one or more rapid drivers (source) producing AF. These drivers may
      be characterized by rapid and regular cycle lengths (CLs), producing fibrillatory
      conduction to the rest of the atria. The ability to reliably identify such
      drivers would be invaluable. The purpose of this study was to develop and
      validate a CL variability detection (CLVD) analysis capable of accurately
      determining beat-to-beat CLs of atrial electrograms (AEGs) during AF, and then to
      compare this analysis with dominant frequency (DF) analysis. METHODS AND RESULTS:
      We analyzed 6 episodes of AF in 6 dogs (sterile pericarditis model) due either to
      a single, stable left atrial reentrant circuit, or unstable reentrant circuits
      causing fibrillatory conduction to the rest of the atria. During AF, AEGs were
      recorded simultaneously from 400 to 420 electrodes on both atria. CLs from over
      20,000 AEGs were manually measured, and compared to CLs detected using both the
      CLVD and DF analyses. There was significant correlation between (1) CLs measured
      manually and the CLVD analysis (mean CL: correlation coefficient [CC]= 0.96,
      standard deviation [SD]: CC = 0.89); and (2) mean CL measured manually and the DF
      analysis (CC = 0.84). However, there was poor correlation between SD of CLs
      measured manually and the organization index (OI) by DF analysis (CC =-0.59).
      CONCLUSION: The CLVD analysis was validated as being accurate for detecting both
      rate and degree of regularity of AEGs during AF, and more accurate than DF
      analysis.

PMID- 23140387
TI  - Driving droplet by scale effect on microstructured hydrophobic surfaces.
AB  - A new type of water droplet transportation mechanism on a microstructured
      hydrophobic surface is proposed and investigated experimentally and
      theoretically: a water droplet could be driven by scale effect under disturbance
      and vibration, which is different from the traditional contact angle-gradient
      based method. A scale-gradient microstructured hydrophobic surface is fabricated
      in which the area fraction is kept constant, but the scales of the micropillars
      are monotonically changed. When additional water or horizontal vibration is
      applied, the original water droplet could move unidirectionally in the direction
      from the small scale to the large scale. A new model with line tension energy
      developed very recently could be used to explain these phenomena. When compared
      with the traditional contact angle-gradient smooth surface, it is also found that
      dynamic contact angle decreases with increasing the scale of the micropillars
      along the moving direction under disturbance. These new findings will deepen our
      understanding of the relationship between topology and dynamic wetting
      properties, and could be very helpful in designing liquid droplet transportation
      devices in microfluidic systems.

PMID- 23140388
TI  - A new lignan with anti-HBV activity from the roots of Bombax ceiba.
AB  - A new lignan bombasinol A (1), together with three known compounds was obtained
      from the ethanol (95%) extract of roots of Bombax ceiba L. through its being
      subjected to silica gel and Sephadex LH-20 chromatography. Their structures were
      elucidated as 4-(4-(3,5-dimethoxyphenyl)hexahydrofuro[3,4-c]furan-1-yl)-2-methoxy
      phenol (1), 5,6-dihydroxymatairesinol (2), (+)-pinoresinol (3) and matairesinol
      (4) on the basis of spectroscopic methods, including 1-D and 2-D NMR (HSQC and
      HMBC) experiments and by comparison of the data with those previously reported
      literatures. All these compounds were the first reported from Bombacaceae. The
      anti-Hepatitis B Virus (HBV) activity of all compounds isolated from B. ceiba in
      the research was evaluated. From the results of the HBV assay, these tested
      compounds showed inhibitory activity against HepG2 2.2.15 cell lines. Compounds 1
      4 showed relative differences in their abilities to inhibit HBsAg secretion, with
      IC50 values of 118.3, 123.7, 118.9 and 218.2 mM, respectively.

PMID- 23140389
TI  - Synthesis, characterization, MCD spectroscopy, and TD-DFT calculations of copper
      metalated nonperipherally substituted octaoctyl derivatives of
      tetrabenzotriazaporphyrin, cis- and trans-tetrabenzodiazaporphyrin,
      tetrabenzomonoazaporphyrin, and tetrabenzoporphyrin.
AB  - Synthesis of the title compounds has been achieved through refinement of a
      recently reported synthetic protocol whereby varying equivalents of MeMgBr are
      reacted with 1,4-dioctylphthalonitrile to produce mixtures favoring specific
      hybrid structures. The initially formed magnesium-metalated compounds are
      obtained as pure materials and include, for the first time, both isomers (cis and
      trans) of tetrabenzodiazaporphyrin. The compounds were demetalated to the metal
      free analogues, which were then converted into the copper-metalated derivatives.
      The X-ray structure of the copper tetrabenzotriazaporphyrin derivative is
      reported. The metal-free and copper-metalated macrocycles exhibit columnar
      mesophase behavior, and it is found that the mesophase stability is unexpectedly
      reduced in the diazaporphyrin derivatives compared to the rest of the series. The
      results of time-dependent density functional theory calculations for the copper
      complexes are compared to the observed optical properties. Michl's perimeter
      model was used as a conceptual framework for analyzing the magnetic circular
      dichroism spectral data, which predicted and accounted for trends in the observed
      experimental spectra.

PMID- 23140390
TI  - Tandem affinity purification in transgenic mouse embryonic stem cells identifies
      DDOST as a novel PPP1CC2 interacting protein.
AB  - Members of the PP1 family of protein phosphatases achieve functional diversity
      through numerous and varied protein-protein interactions. In mammals, there are
      four PP1 isoforms, the ubiquitously expressed PPP1CA, PPP1CB, and PPP1CC1, and
      the testis specific splice isoform PPP1CC2. When the mouse Ppp1cc gene is
      deleted, the only phenotypic consequence is a failure of spermatogenesis in
      homozygous males. To elucidate the function of the Ppp1cc gene, we sought to
      identify novel protein-protein interactions. To this end, we have created SBP
      3XFLAG-PPP1CC1 and SBP-3XFLAG-PPP1CC2 knock-in mouse embryonic stem cell lines
      using a gene-trap-based system. Tandem affinity purification using our knock-in
      cell lines identified 11 significant protein-protein interactions, including nine
      known PP1 interacting proteins and two additional proteins (ATP5C1 and DDOST).
      Reciprocal in vitro sedimentation assays confirmed the interaction between
      PPP1CC2 and DDOST that may have physiological implications in spermatogenesis.
      Immunolocalization studies revealed that DDOST localized to the nuclear envelope
      in dissociated spermatogenic cells and persists throughout spermatogenesis. The
      knock-in system described in this paper can be applied in creating tandem
      affinity-tagged knock-in embryonic stem cell lines with any gene for which a
      compatible gene-trap line is available.

PMID- 23140391
TI  - Participatory ergonomics: co-developing interventions to reduce the risk of
      musculoskeletal symptoms in business drivers.
AB  - The participatory process within four case study organisations with a target
      population of high mileage business drivers is described. The aim was to work
      with drivers and their managers to co-develop intervention activities to raise
      awareness of musculoskeletal health in drivers, including use of the car as a
      mobile office and manual handling from the car. Train-the-trainer sessions were
      delivered in each organisation, along with the co-production of training
      materials. The effectiveness of these activities were evaluated using three
      sources of data: post-intervention questionnaires, interviews with organisation
      'champions' and observations from the research team's diaries. The approach
      raised management awareness of the risks to drivers and was successful in
      affecting change, and as such, participatory research should consider the early
      stages of a project as part of any intervention activities. The research team
      also reflect on conducting applied longitudinal research in the field.
      PRACTITIONER SUMMARY: Raising awareness of the risks of musculoskeletal disorders
      in drivers who work from their vehicle is important. This paper reflects on
      research in the field and provides guidance on the participatory process and
      evaluating intervention activities. The participatory process was successful in
      affecting change at management level.

PMID- 23140392
TI  - The effect of body warming on respiratory system stress recovery in the rat.
AB  - The mechanical characteristics of respiratory system tissues include visco
      elastic behaviour. In particular, after mechanical unloading, i.e., a reduction
      in respiratory system volume, the lower stress achieved slowly increases,
      approaching higher constant value, due to visco-elastic stress recovery. We
      performed experiments in which constant deflation flow arrest was applied in rats
      to study the successive pressure-time course, which defines the visco-elastic
      stress recovery. To investigate the possible effects of temperature changes,
      measurements were performed at two body temperatures, 36.6 +/- 0.3 and 39.0 +/-
      0.1  degrees C. We found that stress recovery is reduced by increasing body
      temperature. Pressure-time curves after deflation arrest were fitted by specific
      mathematical model, and a good agreement was found. Model parameters exhibited
      significant changes with body temperature variations, suggesting that
      temperaturedependent micro-structural rearrangement phenomena in the tissues of
      alveolar wall were involved in the stress recovery decrement with body
      temperature increase. Thus, visco-elastic phenomena in respiratory system tissues
      of mammals exhibit temperature dependence. The stress recovery changes with body
      temperature suggest that expiration is expected to be easier in condition of
      physiological body temperature than in the case of increased temperature.

PMID- 23140393
TI  - The impact of medical education on psychological health of students: a cohort
      study.
AB  - Many studies have shown that the prevalence of psychological distress among
      medical students during medical training is higher than that in general
      population. A few studies have shown that the prevalence of psychological
      distress among medical students before the onset of medical training was similar
      to general population. This study aimed to investigate psychological health of
      medical students before and during medical training. A one-year prospective study
      was done on successful applicants who undergo the first year of medical training
      for 2010/2011 academic session. The stress, anxiety and depression were measured
      by the DASS-21 at five intervals; during interview (Time 0), two months (Time 1),
      four months (Time 2), six months (Time 3) and final examination (Time 4) of the
      first year medical training. The prevalence of unfavourable stress, anxiety and
      depression before the onset of medical training was 4.1%, 55.6% and 1.8%,
      respectively. The prevalence of unfavourable stress during medical training
      ranged between 11.8% and 19.9%. The prevalence of anxiety during medical training
      ranged between 41.1% and 56.7%. The prevalence of depression during medical
      training ranged between 12% and 30%. Mean scores of stress and depression before
      (Time 0) and during medical training (Time 1-4) were significantly different (p <
      0.001). The prevalence and level of unfavourable stress and depression during
      medical training were significantly higher than before the onset medical
      training. This study supports views that medical training is not an optimal
      environment to psychological health of medical students. 

PMID- 23140394
TI  - Molecular assessment of atpase6 mutations associated with artemisinin resistance
      among unexposed and exposed Plasmodium falciparum clinical isolates to
      artemisinin-based combination therapy.
AB  - BACKGROUND: Artemisinin-based combination therapy (ACT) is the mainstay of global
      efforts for treatment of Plasmodium falciparum malaria, but decline in its
      efficacy is the most important obstacle towards malaria control and elimination.
      Therefore, the present molecular analysis provides information on putative
      mutations associated with artemisinin resistance in P. falciparum clinical
      population unexposed and exposed to artesunate 4 years after adoption of ACT as
      the first-line anti-malarial therapy in Iran. METHODS: In this study, blood
      samples (n = 226) were collected from uncomplicated P. falciparum-infected
      patients from different health centers of Chabahar district in Sistan and
      Baluchistan province in the south-eastern part of Iran, during 2003 to 2010. All
      collected isolates were analysed for putative candidate mutations (TTA) L263E
      (GAA), (GAA) E431K (AAA), (GCA) A623E (GAA) and (AGT) S769N (AAT) of pfatpase6
      gene using nested PCR/RFLP, followed by sequencing. Furthermore, the gene copy
      number was assessed by real-time quantitative PCR (RT-qPCR) in the presence of
      SYBR green. RESULTS: Neither the pfatpase6 L263E nor the A623E mutation was
      detected among all examined isolates. The E431K mutation was found in 23% of the
      analysed samples unexposed to ACT; however, it was detected in 17.8% (34/191) of
      P. falciparum isolates exposed to artesunate after 2007. High frequency of this
      single nucleotide polymorphisms (SNP) (overall 18.6%) among both examined groups
      (X2 test, P>0.05) indicated that this SNP should be considered as an unrelated
      mutation to artemisinin resistance. In contrast, S769N mutation was not detected
      in unexposed isolates; however, it was found in 2.6% (5/191), four years after
      introduction of ACT in this malaria setting. Also, detected SNPs were not
      significantly frequent in both unexposed and exposed examined isolates (X2 test,
      P> 0.05). Investigation in the copy number of pfatpase6 gene revealed a similar
      number of copy (n = 1) as in an isolate sensitive to artemisinin. CONCLUSION:
      Taken together, the results suggest, in particular, that pfatpase6 S769N gene
      needs more consideration for its possible association with artesunate resistance
      among P. falciparum isolates.

PMID- 23140396
TI  - Comprehensive profiles of human milk oligosaccharides yield highly sensitive and
      specific markers for determining secretor status in lactating mothers.
AB  - Human milk oligosaccharides (HMOs), as an abundant and bioactive component of
      breast milk, work in many ways to promote the health of breast fed infants. The
      expression of HMOs has been shown to vary in accordance with Lewis blood type and
      secretor status, as women of different blood types differ in the expression of
      alpha1,2 fucosyltransferase (FUT2) and alpha1,3/4 fucosyltransferase (FUT3). In
      this study, HMOs were extracted from the milk of 60 women from The Gambia, Africa
      with various Lewis and secretor blood types. The HMOs were profiled using high
      resolution HPLC-Chip/TOF mass spectrometry. Notably, the amounts of fucosylation
      varied significantly between Le(a+b-) nonsecretors, Le(a-b+) and Le(a-b-)
      secretors, and Le(a-b-) nonsecretors. With higher frequency of expression of the
      recessive Lewis negative and nonsecretor phenotypes in West African populations,
      the HMO profiles of several milks from women of these phenotypes were examined,
      demonstrating decreased amounts of total oligosaccharide abundance and lower
      relative amounts of fucosylation. Also in this study, four specific fucosylated
      structures (2'FL, LNFP I, LDFT, and LNDFH I) were determined to be specific and
      sensitive glycan markers for rapidly determining secretor status without the need
      for serological testing.

PMID- 23140395
TI  - Calpain system protein expression in carcinomas of the pancreas, bile duct and
      ampulla.
AB  - BACKGROUND: Pancreatic cancer, including cancer of the ampulla of Vater and bile
      duct, is very aggressive and has a poor five year survival rate; improved methods
      of patient stratification are required. METHODS: We assessed the expression of
      calpain-1, calpain-2 and calpastatin in two patient cohorts using
      immunohistochemistry on tissue microarrays. The first cohort was composed of 68
      pancreatic adenocarcinomas and the second cohort was composed of 120 cancers of
      the bile duct and ampulla. RESULTS: In bile duct and ampullary carcinomas an
      association was observed between cytoplasmic calpastatin expression and patient
      age (P = 0.036), and between nuclear calpastatin expression and increased tumour
      stage (P = 0.026) and the presence of vascular invasion (P = 0.043). In
      pancreatic cancer, high calpain-2 expression was significantly associated with
      improved overall survival (P = 0.036), which remained significant in multivariate
      Cox-regression analysis (hazard ratio = 0.342; 95% confidence interva l = 0.157
      0.741; P = 0.007). In cancers of the bile duct and ampulla, low cytoplasmic
      expression of calpastatin was significantly associated with poor overall survival
      (P = 0.012), which remained significant in multivariate Cox-regression analysis
      (hazard ratio = 0.595; 95% confidence interval = 0.365-0.968; P = 0.037).
      CONCLUSION: The results suggest that calpain-2 and calpastatin expression is
      important in pancreatic cancers, influencing disease progression. The findings of
      this study warrant a larger follow-up study.

PMID- 23140399
TI  - A Raman scattering study of the interactions of DNA with its water of hydration.
AB  - Raman spectroscopy is used to probe the nature of the hydrogen bonds which hold
      the water of hydration to DNA. The ~ 3450 cm(-1) molecular O-H stretching mode
      shows that the first six water molecules per base pair of the primary hydration
      shell are very strongly bound to the DNA. The observed shift in the peak position
      of this mode permits a determination of the length of the hydrogen bonds for
      these water molecules. These hydrogen bonds appear to be about 0.3 A shorter than
      the hydrogen bonds in bulk water. The linewidth of this mode shows no significant
      changes above water contents of about 15 water molecules per base pair. This
      technique of using a vibrational spectroscopy to obtain structural information
      about the hydration shells of DNA could be used to study the hydration shells of
      other biomolecules. 

PMID- 23140397
TI  - Patient-recorded outcomes and quality of life in evidence-based medicine
      databases on most common ear, throat and nose procedures: a systematic review.
AB  - BACKGROUND: The Cochrane database of systematic reviews is an evidence-based
      medicine (EBM) database that provides the highest quality evidence of the effect
      of various treatments. Quality of life (QoL) is an important aspect when
      treatment effect is considered. OBJECTIVE: To assess how often patient-reported
      outcome measures (PROM), and specifically the quality of life aspect, were
      evaluated in the randomised controlled trial projects (RCTs) included in the
      Cochrane database of systematic reviews of the most common ear, throat and nose
      operations. Also, to explore the same in ongoing trials registered in
      ClinicalTrials.gov. METHODS: Structured literature search. SEARCH STRATEGY AND
      EVALUATION METHOD: The Cochrane database of systematic reviews that evaluated the
      effects of ventilation tube insertion, adenoidectomy, tonsillectomy and
      endoscopic sinus surgery was assessed. The RCTs on which the reviews' conclusions
      were based were explored, and the outcome variables were recorded. A similar
      search was carried out in the ClinicalTrials.gov trial register. RESULTS: In the
      Cochrane database, we identified seven systematic reviews with 30 RCT projects.
      Fourteen (49%) collected some sort of PROM and of those, three (10%) used a
      validated QoL instrument. After the year 2000, the respective figures were 12 of
      15 (80%) and 3 of 15 (20%). In ClinicalTrials.gov, we found 500 ongoing studies
      on the most common ENT operations, nine being RCTs relevant to this review. Five
      (55%) and three (30%) of the ongoing RCTs in ClinicalTrial.gov assess PROM and
      QoL topics in ENT surgery, respectively. CONCLUSIONS: Since the introduction of
      QoL instruments in the 1990s, their use has gradually increased, but validated
      QoL instruments have been used in only one of 10 RCTs included in EBM databases.
      Ongoing RCTs consider QoL only slightly more often.

PMID- 23140400
TI  - Narrow irregular QRS tachycardia with AV dissociation: what is the mechanism?
AB  - A 39-year-old woman with no structural heart disease and frequent episodes of
      sudden onset palpitations was referred for the electrophysiological study. During
      the study, a slightly irregular narrow QRS tachycardia with AV dissociation was
      repeatedly induced and spontaneously terminated. Apparently, irregular cycles and
      termination of the tachycardia were related to the dissociated sinus rhythm:
      atrial depolarizations timed when the AV junction was refractory were able to
      reset the tachycardia, while early atrial depolarizations caused its termination.
      This observation was enough to diagnose the tachycardia mechanism in our case.

PMID- 23140401
TI  - Serum progranulin levels are elevated in patients with systemic lupus
      erythematosus, reflecting disease activity.
AB  - INTRODUCTION: Progranulin (PGRN) is the precursor of granulin (GRN), a soluble
      cofactor for toll-like receptor 9 (TLR9) signaling evoked by oligonucleotide
      (CpG)-DNA. Because TLR9 signaling plays an important role in systemic lupus
      erythematosus (SLE), we investigated whether PGRN is involved in the pathogenesis
      of SLE. METHODS: We measured concentrations of serum PGRN and interleukin-6 (IL
      6) with enzyme-linked immunosorbent assay (ELISA) in patients with SLE (n = 68)
      and in healthy controls (n = 60). We assessed the correlation between the serum
      PGRN levels and established disease-activity indexes. The sera from the patients
      with high PGRN titers (>80 ng/ml) at the initial evaluation were reevaluated
      after the disease was ameliorated by treatment. We also measured the IL-6
      concentration secreted by peripheral blood mononuclear cells (PBMCs) incubated
      with (a) oligonucleotide (CpG-B) in the presence or absence of recombinant human
      PGRN (rhPGRN); and (b) lupus sera in the presence or absence of a neutralizing
      anti-PGRN antibody. RESULTS: Serum PGRN levels were significantly higher in SLE
      patients than healthy controls. Their levels were significantly associated with
      activity of clinical symptoms. They also significantly correlated with values of
      clinical parameters, including the SLE Disease Activity Index and anti-double
      stranded DNA antibody titers, and inversely with CH50, C3, and C4 levels.
      Moreover, serum PGRN levels significantly decreased after successful treatment of
      SLE. The rhPGRN significantly upregulated the production of IL-6 by PBMCs
      stimulated with CpG-B. Patients' sera stimulated production of IL-6 from PBMCs,
      which was significantly impaired by neutralization of PGRN. The serum PGRN levels
      significantly correlated with the serum IL-6 levels. CONCLUSIONS: Serum PGRN
      could be a useful biomarker for disease activity of SLE. PGRN may be involved in
      the pathogenesis of SLE partly by enhancing the TLR9 signaling.

PMID- 23140402
TI  - First experiences in treatment of low-grade glioma grade I and II with proton
      therapy.
AB  - BACKGROUND: To retrospectively assess feasibility and toxicity of proton therapy
      in patients with low-grade glioma (WHO  degrees I/II). PATIENTS AND METHODS:
      Proton beam therapy only administered in 19 patients (median age 29 years; 9
      female, 10 male) for low-grade glioma between 2010 and 2011 was reviewed. In 6
      cases proton therapy was performed due to tumor progression after biopsy, in 8
      cases each due to tumor progression after (partial-) resection, and in 5 cases
      due to tumor progression after chemotherapy. Median total dose applied was 54 GyE
      (range, 48,6-54 GyE) in single fractions of median 1.8 GyE. Median clinical
      target volume was 99 cc (range, 6-463 cc) and treated using median 2 beams
      (range, 1-2). RESULTS: Proton therapy was finished as planned in all cases. At
      end of proton therapy, 13 patients showed focal alopecia, 6 patients reported
      mild fatigue, one patient with temporal tumor localization concentration deficits
      and speech errors and one more patient deficits in short-term memory. Four
      patients did not report any side effects. During follow-up, one patient presented
      with pseudo-progression showing worsening of general condition and brain edema 1
      2 months after last irradiation and restitution after 6 months. In the present MR
      imaging (median follow-up 5 months; range 0-22 months) 12 patients had stable
      disease, 2 (1) patients partial (complete) remission, one more patient pseudo
      progression (differential diagnosis: tumor progression) 4 weeks after irradiation
      without having had further follow-up imaging so far, and one patient tumor
      progression approximately 9 months after irradiation. CONCLUSION: Regarding early
      side effects, mild alopecia was the predominant finding. The rate of alopecia
      seems to be due to large treatment volumes as well as the anatomical locations of
      the target volumes and might be avoided by using multiple beams and the gantry in
      the future. Further evaluations including neuropsychological testing are in
      preparation.

PMID- 23140403
TI  - Antioxidant and cytotoxic activities of Sideritis perezlarae (Borja) Rosello,
      Stubing and Peris.
AB  - Sideritis perezlarae is a plant widely used in folk medicine in the South of
      Andalusia (Cadiz, Spain). In this work, a phytochemical analysis has led to the
      isolation and identification of the flavonoid 7-O- beta -glucosyl-luteolin from a
      methanol extract. The total phenol content estimated by Folin-Ciocalteau assay
      and expressed as gallic acid equivalent per gram of dried fraction, was 102.54 +/
      2.10 mg phenols per gram dry residue. The flavonoid content, investigated by
      AlCl3 reagent, was 23.49 +/- 0.90 mg flavonoids gram dry residue. The methanol
      extract has been evaluated for antioxidant (DPPH and TEAC assays) and cytotoxic
      (SRB assay) properties. In the DPPH radical scavenging assay, the IC50 was 360 ug
      mL(-1). In the total antioxidant activity, calculated by the Trolox equivalent
      antioxidant activity (TEAC, mg g(-1) of dried fraction), the extract showed a
      high antioxidant capacity (TEAC value of 0.59 +/- 0.02 mg g(-1)). The cytotoxic
      activity of the extract against a human adenocarcinoma cell line HT-29 presented
      an IC50 = 69.47 +/- 4.64 ug mL(-1).

PMID- 23140404
TI  - Water redispersible dried nanofibrillated cellulose by adding sodium chloride.
AB  - The present study reports for the first time a method to obtain water
      redispersible dried NFC using freeze-drying. No chemical surface modification was
      required to get this kind of product. Salt addition (sodium chloride: NaCl)
      strategy has been selected to block and then to regenerate hydrogen bonds during
      the drying and the redispersion steps, respectively. Several samples were
      produced at different pH (i.e., 4, 6, 8, and 10). All the redispersed NFC were
      characterized by different techniques (e.g., FE-SEM, XRD, EPMA-EDX) to check the
      effect of salt on NFC aggregation. The interactions between NFC and NaCl at
      different pH conditions have been discussed and the rheology of the redispersed
      NFC suspension has been performed. All the results prove a perfect water
      redispersion at pH 8 and exactly similar suspension is obtained after water
      dispersion of dried NFC following our procedure. These results are very promising
      for increasing application of NFC.

PMID- 23140405
TI  - A smile biases the recognition of eye expressions: configural projection from a
      salient mouth.
AB  - A smile is visually highly salient and grabs attention automatically. We
      investigated how extrafoveally seen smiles influence the viewers' perception of
      non-happy eyes in a face. A smiling mouth appeared in composite faces with
      incongruent non-happy (fearful, neutral, etc.) eyes, thus producing blended
      expressions, or it appeared in intact faces with genuine expressions. Attention
      to the eye region was spatially cued while foveal vision of the mouth was blocked
      by gaze-contingent masking. Participants judged whether the eyes were happy or
      not. Results indicated that the smile biased the evaluation of the eye
      expression: The same non-happy eyes were more likely to be judged as happy and
      categorized more slowly as not happy in a face with a smiling mouth than in a
      face with a non-smiling mouth or with no mouth. This bias occurred when the mouth
      and the eyes appeared simultaneously and aligned, but also to some extent when
      they were misaligned and when the mouth appeared after the eyes. We conclude that
      the highly salient smile projects to other facial regions, thus influencing the
      perception of the eye expression. Projection serves spatial and temporal
      integration of face parts and changes.

PMID- 23140406
TI  - A new method for a quantitative determination of piroxicam in pharmaceutical
      formulations using FT-IR spectrometry.
AB  - A Fourier transform infrared (FT-IR) spectrometric method was developed for the
      rapid, and direct measurement of piroxicam (Pir) in pharmaceutical drugs. Pir is
      a well known and very effective antiinflammatory drug. Pir can be determined by
      various methods and now we are adding a new one that uses a Fourier transform
      infrared spectrophotometric technique. Conventional spectra were compared for
      best determination of active substance in pharmaceutical formulations. The Beer
      Lambert law and two chemometric approaches, partial least squares (PLS) and
      principal component regression (PCR+) methods, were tried in data processing.

PMID- 23140407
TI  - The explanatory power of Schema Theory: theoretical foundations and future
      applications in Ergonomics.
AB  - Schema Theory is intuitively appealing although it has not always received
      positive press; critics of the approach argue that the concept is too ambiguous
      and vague and there are inherent difficulties associated with measuring schemata.
      As such, the term schema can be met with scepticism and wariness. The purpose of
      this paper is to address the criticisms that have been levelled at Schema Theory
      by demonstrating how Schema Theory has been utilised in Ergonomics research,
      particularly in the key areas of situation awareness, naturalistic decision
      making and error. The future of Schema Theory is also discussed in light of its
      potential roles as a unifying theory in Ergonomics and in contributing to our
      understanding of distributed cognition. We conclude that Schema Theory has made a
      positive contribution to Ergonomics and with continued refinement of methods to
      infer and represent schemata it is likely that this trend will continue.
      PRACTITIONER SUMMARY: This paper reviews the contribution that Schema Theory has
      made to Ergonomics research. The criticisms of the theory are addressed using
      examples from the areas of situation awareness, decision making and error.

PMID- 23140409
TI  - A conversation with Dr. Edward Alan Glasper.

PMID- 23140410
TI  - Sudden cardiac arrest in schools: the role of the school nurse in AED program
      implementation.
AB  - A school nurse has many obstacles to overcome when providing emergency care for
      an age group ranging from four to adulthood. The 21st century school nurse faces
      the challenges of providing care to medically fragile children at multiple sites,
      with high student-nurse ratios. The implementation of an Automated External
      Defibrillation (AED) program can assist the school nurse and staff in providing
      necessary life-saving services for Sudden Cardiac Arrest (SCA) victims of all
      ages. The purpose of this article is to describe AED program implementation in a
      school setting, including the need, essential elements, benefits, and potential
      concerns related to this vital component of the American Heart Association five
      link chain of survival.

PMID- 23140411
TI  - The bully at school: an interdisciplinary approach.
AB  - Recent legislation enacted across the United States mandates schools to intervene
      and improve the reporting system of school bullying. Although the laws are an
      extension of safe school mandates, restoring justice in schools has taken a top
      priority. The lack of intensity of current anti-bullying programs and educators
      underestimating the gravity of bullying and its long-term effects on victims is
      problematic. In addition, little emphasis is being placed on understanding the
      research base of children who bully others. A review of the criminology and
      psychiatric research provides insight into the behavior of the bully. Studies
      demonstrate that bullying in school is a "gateway" behavior toward future
      criminal behavior; bullying will persist if professionals do not buy into the
      gravity of chronic child aggressors. Remediation directed at young children is
      essential, concurrent with the provision of teacher training programs focused on
      understanding the common behavioral disorders of childhood. A look at the
      existing research provides direction toward meeting the significant needs of
      children who bully others and perpetuate violence in schools and into adulthood.

PMID- 23140412
TI  - Taking care of my baby: mexican-american mothers in the neonatal intensive care
      unit.
AB  - OBJECTIVES: The admission of an infant to the neonatal intensive care unit (NICU)
      can produce significant stress for mothers and may contribute to a difficult
      transition following discharge. Past research has primarily focused on Caucasian
      women. Mexican-Americans are the fastest growing ethnic population in the U.S.
      with the highest fertility rate; therefore, the purpose of this grounded theory
      study was to gain a better understanding of the NICU experience for Mexican
      American mothers. METHODS: Fifteen women were recruited and data were collected
      through semi-structured interviews. RESULTS: A theoretical model, taking care of
      my baby, was developed. The mothers' experiences began with the unexpected event
      of having an infant admitted to the NICU and played out in a context that
      fluctuated between being supportive (making meaningful connections) or inhibitive
      (struggling to mother). The women developed strategies to help them take care of
      their babies during the NICU stay: balancing responsibilities, leaving part of me
      with my baby, and watching over. The process concluded in one of two ways:
      bringing my baby home or losing my baby. CONCLUSION: These findings offer insight
      for neonatal nurses who provide care for Mexican-American NICU mothers and may
      help inform their practice. Further research is needed with this growing
      population to ensure supportive nursing care and influence positive outcomes.

PMID- 23140413
TI  - Effects of an internet intervention on mothers' psychological, parenting, and
      health care utilization outcomes.
AB  - AIMS AND OBJECTIVES: The purpose of this pilot study was to test the effects of
      an Internet-based intervention, the New Mothers Network, on single, low-income,
      adolescent, African American mothers' psychological, parenting, and health care
      utilization outcomes. BACKGROUND: The study was based on social support theory.
      METHODS: For mothers in the Intervention Group, MSNTVTM was installed in
      subjects' homes and connected to the Internet. Data were collected at 1 week, 6
      weeks, 3 months, and 6 months following the infant's birth. RESULTS: For infant
      health services utilization, 70.6% of those in the Control Group took their
      infant to the emergency room at least once during the study compared to 35.7% of
      mothers in the Intervention Group. The New Mothers Network allowed mothers to
      share their experiences and acquire information from nurses about caring for
      themselves and their infants. CONCLUSION: The New Mothers Network Web site is
      well poised for nursing driven social support intervention via the Internet, even
      though access devices are evolving over time.

PMID- 23140414
TI  - Maladaptive behaviors of children with autism: parent support, stress, and
      coping.
AB  - BACKGROUND: The estimated prevalence of Autism Spectrum Disorder (ASD) is one in
      88. Autism Spectrum Disorders are nearly five times more common among boys than
      girls. Children with autism may develop a variety of socially unacceptable
      maladaptive behaviors beyond the defining symptoms of the spectrum disorder.
      AIMS: It is necessary to conduct research to examine maladaptive behaviors of
      children with autism, family supports, parental stress, and parental coping.
      METHODS: Data used were collected during an earlier descriptive, correlational,
      cross-sectional study. Using the Double ABCX Model of family behavior as the
      framework, this study evaluated parents' views of the adaptive behaviors of their
      children diagnosed with autism using the networks of support for their family,
      parental stress, and parental coping patterns. RESULTS: Results indicate an
      association between increased Internalizing maladaptive behaviors and increased
      parental stress (r = .547, p = .000). CONCLUSIONS: The findings of this study
      suggest that parents of children with autism report that their children have
      clinically significant maladaptive behaviors. Healthcare providers could use
      results from this study to provide appropriate intervention for maladaptive
      behaviors to support children with autism and their families.

PMID- 23140416
TI  - Effects of structure dissymmetry on aggregation behaviors of quaternary ammonium
      Gemini surfactants in a protic ionic liquid EAN.
AB  - The aggregation behaviors of a series of dissymmetric cationic Gemini
      surfactants, [C(m)H(2m+1)(CH(3))(2)N(CH(2))(2)N(CH(3))(2)C(n)H(2n+1)]Br(2),
      designated as m-2-n (with a fixed m + n = 24, m = 16, 14, 12) have been
      investigated in a protic ionic liquid, ethylammonium nitrate (EAN). Surface
      tension, polarized optical microscopy (POM), small-angle X-ray scattering (SAXS),
      and rheological measurements are adopted to investigate the micellization and
      lyotropic liquid crystal (LLC) formation. The obtained results indicate that the
      structure dissymmetry plays an important role in aggregation process of m-2-n.
      With increasing degree of dissymmetry, the critical micellization concentration,
      the maximum reduction of solvent surface tension, and the minimum area occupied
      per surfactant molecule at the air/EAN interface all become smaller. The
      thermostability of formed LLCs is therefore improved because of the more compact
      molecules. These characteristics can be explained by the enhancement of
      solvophobic effect due to the increased structure dissymmetry of Gemini
      surfactants.

PMID- 23140417
TI  - Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women.
AB  - BACKGROUND: Vitamin K2 contributes to bone and cardiovascular health. Therefore,
      two vitamin K2 homologues, menaquinone-4 (MK-4) and menaquinone-7 (MK-7), have
      been used as nutrients by the food industry and as nutritional supplements to
      support bone and cardiovascular health. However, little is known about the
      bioavailability of nutritional MK-4. To investigate MK-4 and MK-7
      bioavailability, nutritional doses were administered to healthy Japanese women.
      FINDINGS: Single dose administration of MK-4 (420 MUg; 945 nmol) or MK-7 (420
      MUg; 647 nmol) was given in the morning together with standardized breakfast. MK
      7 was well absorbed and reached maximal serum level at 6 h after intake and was
      detected up to 48 h after intake. MK-4 was not detectable in the serum of all
      subjects at any time point. Consecutive administration of MK-4 (60 MUg; 135 nmol)
      or MK-7 (60 MUg; 92 nmol) for 7 days demonstrated that MK-4 supplementation did
      not increase serum MK-4 levels. However, consecutive administration of MK-7
      increased serum MK-7 levels significantly in all subjects. CONCLUSIONS: We
      conclude that MK-4 present in food does not contribute to the vitamin K status as
      measured by serum vitamin K levels. MK-7, however significantly increases serum
      MK-7 levels and therefore may be of particular importance for extrahepatic
      tissues.

PMID- 23140418
TI  - The influence of a complete lower denture destabilization on the pressure of the
      mucous membrane foundation.
AB  - The results of previous studies on the pressures beneath the mucous membrane
      supported dentures are contrary to the prevailing pain sensations and discomfort
      reported in practice. In this work, a FEM analysis of large displacements was
      used for calculation of the contact stresses beneath a lower denture that
      accompany destabilization under the realistic oblique mastication forces and
      stabilization of a non-working flange at the balancing contacts. The pressure on
      the surface of a mucous membrane beneath a denture that was loaded in a stable
      manner with a vertical occlusal force of 100 N was lower than the pain threshold.
      It was even more surprising as the extremely unfavorable lower denture foundation
      conditions were selected for this analysis. The lateral mastication forces
      destabilized the denture by means of tilting it and reducing its supporting area.
      Significant pressures calculated for the destabilization are consistent with the
      clinically observed decrease or a complete lack of chewing efficiency in the
      cases of unfavorable foundation conditions. A fundamental importance of the
      balancing contacts for the chewing efficiency was confirmed quantitatively. A
      remarkable development which has been achieved in the modeling of the denture
      functioning conditions is crucial for further biomechanical investigations of the
      mucous membrane-supported dentures, as well as for the implant-retained dentures.

PMID- 23140419
TI  - Testing of human papillomavirus in lung cancer and non-tumor lung tissue.
AB  - BACKGROUND: Risk factors for lung cancer, such as cigarette smoking,
      environmental pollution, asbestos, and genetic determinants, are well-known,
      whereas involvement of the human papillomavirus (HPV) is still unclear. METHODS:
      We examined a series of 100 lung cancer patients from Italy and the UK for the
      presence of HPV DNA in both lung tumor specimens and adjacent non-tumoral
      specimens from the same patients. Thirty-five of the most clinically relevant HPV
      types were assayed using PCR amplification of the highly conserved L1 region of
      the viral genome followed by hybridization with specific probes. RESULTS: No HPV
      was detected in tumor specimens nor in normal lung tissue of any patient.
      CONCLUSIONS: These data indicate that, in this Western series, HPV is not
      associated with the risk of lung cancer. Our findings will help refine estimates
      of lung cancer risk in patients affected by a common viral infection involved in
      other types of human cancer.

PMID- 23140420
TI  - Cell-free DNA and outcome in sepsis.
AB  - Severe sepsis can be a catastrophic condition that is often associated with poor
      outcomes. The early diagnosis and management of the condition are vital in order
      to improve the chances of survival. However, owing to the syndromal nature of its
      definition and the lack of a biomarker able to accurately confirm the condition,
      the diagnosis of sepsis is challenging. Even more challenging is the prediction
      of how these patients will respond to the therapy and whether they will survive
      the intensive care and the hospital admission. 

PMID- 23140421
TI  - Adult and paediatric tonsillectomy: a two cycle audit of Scottish Intercollegiate
      Guidelines Network 117 in a total of one hundred and sixty nine patients.

PMID- 23140422
TI  - Comparison of GPU- and CPU-implementations of mean-firing rate neural networks on
      parallel hardware.
AB  - Modern parallel hardware such as multi-core processors (CPUs) and graphics
      processing units (GPUs) have a high computational power which can be greatly
      beneficial to the simulation of large-scale neural networks. Over the past years,
      a number of efforts have focused on developing parallel algorithms and simulators
      best suited for the simulation of spiking neural models. In this article, we aim
      at investigating the advantages and drawbacks of the CPU and GPU parallelization
      of mean-firing rate neurons, widely used in systems-level computational
      neuroscience. By comparing OpenMP, CUDA and OpenCL implementations towards a
      serial CPU implementation, we show that GPUs are better suited than CPUs for the
      simulation of very large networks, but that smaller networks would benefit more
      from an OpenMP implementation. As this performance strongly depends on data
      organization, we analyze the impact of various factors such as data structure,
      memory alignment and floating precision. We then discuss the suitability of the
      different hardware depending on the networks' size and connectivity, as random or
      sparse connectivities in mean-firing rate networks tend to break parallel
      performance on GPUs due to the violation of coalescence.

PMID- 23140423
TI  - Self-assembled protein arrays from an Ornithodoros moubata salivary gland
      expression library.
AB  - Protein interactions play a critical role in the regulation of many biological
      events and their study in a high-throughput format has become a key area of
      proteomic research. Nucleid Acid Programmable Protein Arrays (NAPPA) technology
      allows the construction of protein arrays from cDNA expression libraries in high
      throughput cell-free systems to study protein interaction and functions. Tick
      saliva contains antihemostatic, anti-inflammatory, and immunosuppressive proteins
      that counteract the host hemostatic, immune, and inflammatory responses allowing
      the ingestion of host blood and facilitating its infection by the tick-borne
      pathogens. Identification of such proteins and their functions could help in the
      selection of antigenic targets for the development of antitick and transmission
      blocking vaccines. With that aim, we have prepared a cDNA expression library from
      the salivary glands of Ornithodoros moubata and subsequently produced a self
      assembled protein microarray using 480 randomly selected clones from that
      library. The reproducibility of the array, its representativeness of the tick
      salivary protein repertoire, and the functionality of the in situ expressed
      proteins have been checked, demonstrating that it is a suitable tool for the
      identification and functional characterization of soft tick salivary molecules
      that interact with host proteins. Several clones in the array were shown to bind
      to human recombinant P-selectin. One of them was a likely secreted tick
      phospholipase A2, which may represent a potential new ligand for P-selectin. As
      these salivary molecules are likely involved in blood meal acquisition through
      the modulation of the host immune and hemostatic responses, this new high
      throughput tool could open new avenues for development of new therapeutic agents
      and control strategies against ticks and tick-borne pathogens.

PMID- 23140424
TI  - New secondary metabolites from bioactive extracts of the fungus Armillaria
      tabescens.
AB  - Ethyl acetate extracts of Armillaria tabescens (strain JNB-OZ344) showed
      significant fungistatic and bacteristatic activities against several major human
      pathogens including Candida albicans, Cryptococcus neoformans, Escherichia coli
      and Mycobacterium intracellulare. Chemical analysis of these extracts led to the
      isolation and identification of four new compounds, emestrin-F (1), emestrin-G
      (2), 6-O-(4-O-methyl-beta-D-glucopyranosyl)-8-hydroxy-2,7-dimethyl-4H-benzopyran
      4-one (3) and cephalosporolide-J (4), along with five other previously known
      compounds, emestrin (5), cephalosporolide-E (6), decarestrictine-C2 (7),
      ergosterol and brassicasterol. Structural elucidation of all compounds was
      carried out by NMR and MS analyses. Antimicrobial assays revealed that compounds
      1 and 5 were responsible for the observed growth inhibitory activities of the
      fungal extracts against the human pathogens tested.

PMID- 23140426
TI  - Of mad cows and bolted horses: the economics of blood safety.

PMID- 23140425
TI  - A validation of carbon fiber imaging couch top modeling in two radiation therapy
      treatment planning systems: Philips Pinnacle3 and BrainLAB iPlan RT Dose.
AB  - BACKGROUND: Carbon fiber (CF) is now the material of choice for radiation therapy
      couch tops. Initial designs included side metal bars for rigidity; however, with
      the advent of IGRT, involving on board imaging, new thicker CF couch tops without
      metal bars have been developed. The new design allows for excellent imaging at
      the expense of potentially unacceptable dose attenuation and perturbation.
      OBJECTIVES: We set out to model the BrainLAB imaging couch top (ICT) in Philips
      Pinnacle(3) treatment planning system (TPS), to validate the already modeled ICT
      in BrainLAB iPlan RT Dose treatment planning system and to compute the magnitude
      of the loss in skin sparing. RESULTS: Using CF density of 0.55 g/cm(3) and foam
      density of 0.03 g/cm(3), we demonstrated an excellent agreement between measured
      dose and Pinnacle(3) TPS computed dose using 6 MV beam. The agreement was within
      1% for all gantry angle measured except for 120 degrees , which was 1.8%. The
      measured and iPlan RT Dose TPS computed dose agreed to within 1% for all gantry
      angles and field sizes measured except for 100 degrees  where the agreement was
      1.4% for 10 cm * 10 cm field size. Predicted attenuation through the couch by
      iPlan RT Dose TPS (3.4% - 9.5%) and Pinnacle(3) TPS (2% - 6.6%) were within the
      same magnitude and similar to previously reported in the literature. Pinnacle(3)
      TPS estimated an 8% to 20% increase in skin dose with increase in field size.
      With the introduction of the CF couch top, it estimated an increase in skin dose
      by approximately 46 - 90%. The clinical impact of omitting the couch in treatment
      planning will be dependent on the beam arrangement, the percentage of the beams
      intersecting the couch and their angles of incidence. CONCLUSION: We have
      successfully modeled the ICT in Pinnacle(3) TPS and validated the modeled ICT in
      iPlan RT Dose. It is recommended that the ICT be included in treatment planning
      for all treatments that involve posteriors beams. There is a significant increase
      in skin dose that is dependent on the percentage of the beam passing through the
      couch and the angle of incidence.

PMID- 23140427
TI  - Encouraging high-quality research publications from the developing world.

PMID- 23140428
TI  - Retrograde patient blood flow and rouleaux preventing red blood cell transfusion.

PMID- 23140430
TI  - Obstetric and trauma database review at a single institution finds the optimal
      maternal age restriction for the transfusion of O- blood to women involved in
      trauma to be 45 years.

PMID- 23140431
TI  - In reply to: "Is the SCID mouse model applicable to human acute lung injury?".

PMID- 23140434
TI  - Successful use of citrate anticoagulant with heparin bolus for excessive clotting
      during extracorporeal photopheresis.

PMID- 23140435
TI  - Spectroscopic and computational studies of a small-molecule functional mimic of
      iron superoxide dismutase, iron 2,6-diacetylpyridinebis(semioxamazide).
AB  - Iron 2,6-diacetylpyridinebis(semioxamazide) (Fe(dapsox)) is a heptacoordinate
      pentagonal bipyramidal, functional mimic of iron-dependent superoxide dismutase
      that has been well-characterized on the basis of kinetics and mechanistic
      studies; however, prior to our studies, its electronic structure had yet to be
      examined. This paper details our initial characterization of Fe(dapsox) in both
      its reduced and oxidized states, by electronic absorption (Abs) and low
      temperature magnetic circular dichroism spectroscopies. Density functional theory
      (DFT) geometry optimizations have yielded models in good agreement with the
      published crystal structures. Time-dependent DFT and INDO/S-CI calculations
      performed on these models successfully reproduce the experimental Abs spectra and
      identify intense, low-energy transitions in the reduced complex
      (Fe(II)(H(2)dapsox)) as metal-to-ligand charge transfer transitions, suggesting
      the presence of pi-backbonding in this complex. This backbonding, along, with the
      proton uptake accompanying metal ion reduction, provides a compelling mechanism
      by which the metal-centered redox potential is correctly tuned for catalytic
      superoxide disproportionation.

PMID- 23140437
TI  - Bridging the dimensions of research on cardiac ryanodine receptor mutations.

PMID- 23140436
TI  - A possible strategy against head and neck cancer: in silico investigation of
      three-in-one inhibitors.
AB  - Overexpression of epidermal growth factor receptor (EGFR), Her2, and
      uroporphyrinogen decarboxylase (UROD) occurs in a variety of malignant tumor
      tissues. UROD has potential to modulate tumor response of radiotherapy for head
      and neck cancer, and EGFR and Her2 are common drug targets for the treatment of
      head and neck cancer. This study attempts to find a possible lead compound
      backbone from TCM Database@Taiwan ( http://tcm.cmu.edu.tw/ ) for EGFR, Her2, and
      UROD proteins against head and neck cancer using computational techniques.
      Possible traditional Chinese medicine (TCM) lead compounds had potential binding
      affinities with EGFR, Her2, and UROD proteins. The candidates formed stable
      interactions with residues Arg803, Thr854 in EGFR, residues Thr862, Asp863 in
      Her2 protein, and residues Arg37, Arg41 in UROD protein, which are key residues
      in the binding or catalytic domain of EGFR, Her2, and UROD proteins. Thus, the
      TCM candidates indicated a possible molecule backbone for evolving potential
      inhibitors for three drug target proteins against head and neck cancer.

PMID- 23140438
TI  - Evaluation of two working methods for screed floor layers on musculoskeletal
      complaints, work demands and workload.
AB  - Screed floors are bound by sand-cement (SF) or by anhydrite (AF). Sand-cement
      floors are levelled manually and anhydrite floors are self-levelling and
      therefore differences in work demands and prevalences of musculoskeletal
      complaints might occur. The objective was to assess among SF layers and AF layers
      (1) the prevalence of musculoskeletal complaints and (2) the physical work
      demands, energetic workload, perceived workload and discomfort. A questionnaire
      survey and an observational field study were performed. Compared with AF layers
      (n = 35), SF layers (n = 203) had higher, however, not statistically significant
      different, prevalences of neck (20% vs. 7%), shoulder (27% vs. 13%), low back
      (39% vs. 26%) and ankles/feet (9% vs. 0%) complaints. Sand-cement-bound screed
      floor layers (n = 18) bent and kneeled significantly longer (Delta77 min and
      Delta94 min; respectively), whereas AF layers (n = 18) stood significantly longer
      (Delta60 min). The work demands of SF layers exceeded exposure criteria for low
      back and knee complaints and therefore new working measures should be developed
      and implemented. PRACTITIONER SUMMARY: In comparison with anhydrite-bound screed
      floor layers, sand-cement-bound screed floor layers exceeded exposure criteria
      for work-related low back and knee complaints. New working methods and measures
      for sand-cement-bound screed floor layers should be developed and implemented to
      reduce the risk for work-related musculoskeletal complaints.

PMID- 23140439
TI  - Social media is shifting power from advertisers to consumers.

PMID- 23140442
TI  - In vivo biodistribution of amino-functionalized ceria nanoparticles in rats using
      positron emission tomography.
AB  - A variety of nanoparticles have been proposed for several biomedical
      applications. To gauge the therapeutic potential of these nanoparticles, in vivo
      biodistribution is essential and mandatory. In the present study, ceria
      nanoparticles (5 nm average particle size) were labeled with (18)F to study their
      in vivo biodistribution in rats by positron emission tomography (PET). The (18)F
      isotope was anchored by reaction of N-succinimidyl 4-[(18)F]fluorobenzoate ((18)F
      SFB) with a modified nanoparticle surface obtained by silylation with 3
      aminopropylsilyl. Radiolabeled ceria nanoparticles accumulated mainly in lungs,
      spleen, and liver. Metabolic products of the radiolabeled nanoparticulate
      material were excreted into the urinary tract. 

PMID- 23140443
TI  - Instance memorization and category influence: challenging the evidence for
      multiple systems in category learning.
AB  - A class of dual-system theories of categorization assumes a categorization system
      based on actively formed prototypes in addition to a separate instance memory
      system. It has been suggested that, because they have used poorly differentiated
      category structures (such as the influential "5-4" structure), studies supporting
      the alternative exemplar theory reveal little about the properties of the
      categorization system. Dual-system theories assume that the instance memory
      system only influences categorization behaviour via similarity to single isolated
      instances, without generalization across instances. However, we present the
      results of two experiments employing the 5-4 structure to argue against this.
      Experiment 1 contrasted learning in the standard 5-4 structure with learning in
      an even more poorly differentiated 5-4 structure. In Experiment 2, participants
      memorized the 5-4 structure based on a five minute simultaneous presentation of
      all nine category instances. Both experiments revealed category influences as
      reflected by differences in instance learnability and generalization, at variance
      with the dual-system prediction. These results have implications for the
      exemplars versus prototypes debate and the nature of human categorization
      mechanisms.

PMID- 23140444
TI  - Cancer and non-cancer health effects from food contaminant exposures for children
      and adults in California: a risk assessment.
AB  - BACKGROUND: In the absence of current cumulative dietary exposure assessments,
      this analysis was conducted to estimate exposure to multiple dietary contaminants
      for children, who are more vulnerable to toxic exposure than adults. METHODS: We
      estimated exposure to multiple food contaminants based on dietary data from
      preschool-age children (2-4 years, n=207), school-age children (5-7 years,
      n=157), parents of young children (n=446), and older adults (n=149). We compared
      exposure estimates for eleven toxic compounds (acrylamide, arsenic, lead,
      mercury, chlorpyrifos, permethrin, endosulfan, dieldrin, chlordane, DDE, and
      dioxin) based on self-reported food frequency data by age group. To determine if
      cancer and non-cancer benchmark levels were exceeded, chemical levels in food
      were derived from publicly available databases including the Total Diet Study.
      RESULTS: Cancer benchmark levels were exceeded by all children (100%) for
      arsenic, dieldrin, DDE, and dioxins. Non-cancer benchmarks were exceeded by >95%
      of preschool-age children for acrylamide and by 10% of preschool-age children for
      mercury. Preschool-age children had significantly higher estimated intakes of 6
      of 11 compounds compared to school-age children (p<0.0001 to p=0.02). Based on
      self-reported dietary data, the greatest exposure to pesticides from foods
      included in this analysis were tomatoes, peaches, apples, peppers, grapes,
      lettuce, broccoli, strawberries, spinach, dairy, pears, green beans, and celery.
      CONCLUSIONS: Dietary strategies to reduce exposure to toxic compounds for which
      cancer and non-cancer benchmarks are exceeded by children vary by compound. These
      strategies include consuming organically produced dairy and selected fruits and
      vegetables to reduce pesticide intake, consuming less animal foods (meat, dairy,
      and fish) to reduce intake of persistent organic pollutants and metals, and
      consuming lower quantities of chips, cereal, crackers, and other processed
      carbohydrate foods to reduce acrylamide intake.

PMID- 23140445
TI  - Special issue on "Neural Network Simulation".

PMID- 23140446
TI  - Physical properties and antimicrobial efficacy of thyme oil nanoemulsions:
      influence of ripening inhibitors.
AB  - Thyme oil-in-water nanoemulsions (pH 3.5) were prepared as potential
      antimicrobial delivery systems. The nanoemulsions were highly unstable to droplet
      growth and phase separation, which was attributed to Ostwald ripening due to the
      relatively high water solubility of thyme oil. Ostwald ripening could be
      inhibited by mixing thyme oil with a water-insoluble ripening inhibitor (>=60 wt
      % corn oil or >=50 wt % MCT in the lipid phase) before homogenization, yielding
      nanoemulsions with good physical stability. Physically stable thyme oil
      nanoemulsions were examined for their antimicrobial activities against an acid
      resistant spoilage yeast, Zygosaccharomyces bailii (ZB). Oil phase composition
      (ripening inhibitor type and concentration) had an appreciable influence on the
      antimicrobial activity of the thyme oil nanoemulsions. In general, increasing the
      ripening inhibitor levels in the lipid phase reduced the antimicrobial efficacy
      of nanoemulsions. For example, for nanoemulsions containing 60 wt % corn oil in
      the lipid phase, the minimum inhibitory concentration (MIC) of thyme oil to
      inhibit ZB growth was 375 MUg/mL, while for nanoemulsions containing 90 wt % corn
      oil in the lipid phase, even 6000 MUg/mL thyme oil could not inhibit ZB growth.
      This effect is also dependent on ripening inhibitor types: at the same
      concentration in the lipid phase, MCT decreased the antimicrobial efficacy of
      thyme oil more than corn oil. For instance, when the level of ripening inhibitor
      in the lipid phase was 70 wt %, the MICs of thyme oil for nanoemulsions
      containing corn oil and MCT were 750 and 3000 MUg/mL, respectively. The results
      of this study have important implications for the design and utilization of
      nanoemulsions as antimicrobial delivery systems in the food and other industries.

PMID- 23140448
TI  - Rapid detection of recurrent intraventricular hemorrhage by ultrasound in a
      multiple trauma patient who had undergone craniectomy.
AB  - Ultrasound may be a useful tool to evaluate intracranial abnormalities in
      critically ill patients undergoing decompressive craniectomy. We present a
      multiple trauma patient who had undergone craniectomy and in whom recurrent
      intraventricular hemorrhage and patterns of cerebral blood flow were rapidly
      detected by ultrasound. 

PMID- 23140447
TI  - The effect of lipoprotein-associated phospholipase A2 deficiency on pulmonary
      allergic responses in Aspergillus fumigatus sensitized mice.
AB  - BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2)/platelet-activating
      factor acetylhydrolase (PAF-AH) has been implicated in the pathogenesis of
      cardiovascular disease. A therapeutic targeting of this enzyme was challenged by
      the concern that increased circulating platelet activating factor (PAF) may
      predispose to or increase the severity of the allergic airway response. The aim
      of this study was to investigate whether Lp-PLA2 gene deficiency increases the
      risk of PAF and IgE-mediated inflammatory responses in vitro and in vivo using
      mouse models. METHODS: Lp-PLA2-/- mice were generated and back crossed to the
      C57BL/6 background. PAF-AH activity was measured using a hydrolysis assay in
      serum and bronchoalveolar lavage (BAL) samples obtained from mice. Aspergillus
      fumigatus (Af)-specific serum was prepared for passive allergic sensitization of
      mice in vivo and mast cells in vitro. beta- hexosaminidase release was studied in
      bone marrow derived mast cells sensitized with Af-specific serum or DNP-IgE and
      challenged with Af or DNP, respectively. Mice were treated with
      lipopolysaccharide (LPS) and PAF intratracheally and studied 24 hours later. Mice
      were sensitized either passively or actively against Af and were studied 48 hours
      after a single intranasal Af challenge. Airway responsiveness to methacholine,
      inflammatory cell influx in the lung tissue and BAL, immunoglobulin (ELISA) and
      cytokine (Luminex) profiles were compared between the wild type (WT) and Lp-PLA2
      /- mice. RESULTS: PAF-AH activity was reduced but not completely abolished in Lp
      PLA2-/- serum or by in vitro treatment of serum samples with a high saturating
      concentration of the selective Lp-PLA2 inhibitor, SB-435495. PAF inhalation
      significantly enhanced airway inflammation of LPS treated WT and Lp-PLA2-/- mice
      to a similar extent. Sensitized WT and Lp-PLA2-/- bone-marrow derived mast cells
      released beta-hexosaminidase following stimulation by allergen or IgE
      crosslinking to equivalent levels. Wild type and Lp-PLA2-/- mice responded to
      passive or active allergic sensitization by significant IgE production, airway
      inflammation and hyperresponsiveness after Af challenge. BAL cell influx was not
      different between these strains while IL-4, IL-5, IL-6 and eotaxin release was
      attenuated in Lp-PLA2-/- mice. There were no differences in the amount of total
      IgE levels in the Af sensitized WT and Lp-PLA2-/- mice. CONCLUSIONS: We conclude
      that Lp-PLA2 deficiency in C57BL/6 mice did not result in a heightened airway
      inflammation or hyperresponsiveness after PAF/LPS treatment or passive or active
      allergic sensitization and challenge.

PMID- 23140449
TI  - The effectiveness of rigid pericardial endoscopy for minimally invasive minor
      surgeries: cell transplantation, epicardial pacemaker lead implantation, and
      epicardial ablation.
AB  - BACKGROUND: The efficacy and safety of rigid pericardial endoscopy as the
      promising minimally invasive approach to the pericardial space was evaluated.
      Techniques for cell transplantation, epicardial pacemaker lead implantation, and
      epicardial ablation were developed. METHODS: Two swine and 5 canines were studied
      to evaluate the safety and efficacy of rigid pericardial endoscopy. After a
      double pericardiocentesis, a transurethral rigid endoscope was inserted into the
      pericardial space. The technique to obtain a clear visual field was examined, and
      acute complications such as hemodynamic changes and the effects on intra
      pericardial pressure were evaluated. Using custom-made needles, pacemaker leads,
      and forceps, the applications for cell transplantation, epicardial pacemaker lead
      implantation, and epicardial ablation were also evaluated. RESULTS: The use of
      air, the detention of a stiff guide wire in the pericardial space, and the
      stretching of the pericardium with the rigid endoscope were all useful to obtain
      a clear visual field. A side-lying position also aided observation of the
      posterior side of the heart. As a cell transplantation methodology, we developed
      an ultrasonography-guided needle, which allows for the safe visualization of
      transplantation without major complications. Pacemaker leads were safely and
      properly implanted, which provides a better outcome for cardiac resynchronizing
      therapy. Furthermore, the success of clear visualization of the pulmonary veins
      enabled us to perform epicardial ablation. CONCLUSIONS: Rigid pericardial
      endoscopy holds promise as a safe method for minimally invasive cell
      transplantation, epicardial pacemaker lead implantation, and epicardial ablation
      by allowing clear visualization of the pericardial space.

PMID- 23140450
TI  - Identifying the CHO secretome using mucin-type O-linked glycosylation and click
      chemistry.
AB  - Chinese hamster ovary cells (CHO) are the most common cell line used in the
      production of therapeutic proteins. Understanding the complex pattern of secreted
      host cell proteins (HCP) that are released by CHO cells will facilitate the
      development of new recombinant protein production processes. In this study, we
      have adapted the N-azido-galactosamine (GalNAz) metabolic labeling method to
      enable the mass spectrometry identification and quantification of secreted
      proteins in cell culture media. CHO DG44 and CHO-S cells were cultured in media
      containing GalNAz, which was metabolically incorporated into mucin-type O-linked
      glycans of secreted proteins. These proteins were effectively enriched using
      click-chemistry from the cell culture media, allowing for the analysis of
      secreted proteins across multiple days of cell growth. When compared to the
      standard method for secretome analysis, the GalNAz method not only increased the
      total number of proteins identified but dramatically improved the quality of data
      by decreasing the number of background proteins (cytosolic or nuclear) to
      essentially zero.

PMID- 23140451
TI  - Endocytosis, intracellular traffic and fate of cell penetrating peptide based
      conjugates and nanoparticles.
AB  - The insides of cells can be viewed as a treasure trove of targets for therapeutic
      intervention of diseases or as deposits for contrasting agents. Increasingly the
      molecules that need to be delivered to the inside of cells for these purposes are
      macromolecular and membrane impermeable. Cell penetrating peptides (CPPs) have
      proven abilities to deliver a range of macromolecular cargo into cells thus
      raising their profile as potential delivery vectors for wide-ranging
      applications. There is evidence to suggest that CPPs first enter cells through
      endocytosis and that cytosolic delivery is mediated across endolysosomal
      membranes. Their capacity to do this, over direct plasma membrane translocation,
      is likely to depend on the nature and size of the cargo. Cells use a range of
      endocytic routes to facilitate entry from well characterised pathways regulated
      by clathrin to more recently discovered and less characterised pathways regulated
      by clathrin independent mechanisms. These are likely to determine the
      intracellular fate of cell delivery vectors including those based on cell
      penetrating peptides. Thus gaining accurate knowledge of their endocytic uptake
      and traffic is an important characterisation criteria for progress in this field.
      This review describes the different endocytic pathways that have been identified
      in mammalian cells and specific reports that have studied the uptake mechanisms
      and endocytic traffic of cell penetrating peptides and their associated cargo.
      These cargoes range from short peptides to an increasing library of nanoparticles
      such as quantum dots, liposomes and polymeric dendrimers. The studies highlight
      the effectiveness of cell penetrating peptides for delivering these entities into
      a diverse array of cell types using different endocytic pathways. This is shown
      using microscopy based colocalisation analysis with the few specific endocytic
      probes available, and chemical inhibitors of endocytosis that suffer from lack of
      specificity. Overall, more specific probes, inhibitors and novel technologies are
      required for accurate characterisation of cellular dynamics of cell penetrating
      peptide conjugates thus allowing them to reach their full potential as vectors
      for therapeutics and other payloads.

PMID- 23140452
TI  - Everything you always wanted to know about CADY-mediated siRNA delivery* (* but
      afraid to ask).
AB  - Although siRNA consist in very promising therapeutics, their clinical development
      is limited by several biological barriers including low cellular permeability,
      poor stability and lack of tissue specificity. Therefore the Achilles' heel for
      siRNA-based therapy is directly related to the lack of efficient system to
      promote their delivery. During the last two decades, cell-penetrating peptides
      (CPPs) have been widely developed to enhance the cellular delivery of
      therapeutics. In this context we have elaborated a new strategy based on self
      assembling peptide-based nanoparticles. The CADY peptide is a 20-residue
      secondary amphipathic peptide which is able to spontaneously self associate with
      siRNA with a strong affinity, by combining both electrostatic and hydrophobic
      interactions, to form stable nanoparticles. Investigations of both physico
      chemical properties and cellular siRNA delivery revealed that the CADY/siRNA
      complexes were able to enter a wide variety of cell lines by a mechanism
      independent of any endocytotic pathway. In addition a deeper understanding of the
      self assembly of CADY molecules around siRNA leads to a "raspberry"-like
      nanoparticle architecture which provides new perspectives for the CADY/siRNA
      formulations. Finally the robustness of the biological response infers that
      peptide-based nanoparticle technology holds a strong promise for therapeutic
      applications. The present review deals with most of the biophysical
      characteristics as well as the cellular mechanism and cellular applications of
      CADY/siRNA nanoparticles.

PMID- 23140453
TI  - Cell-penetrating peptides as nucleic acid delivery systems: from biophysics to
      biological applications.
AB  - The increasing knowledge on the genetic basis of disease has allowed the
      development of promising gene-targeted therapies that can be applied to numerous
      diseases. Such genetic-based approaches involve the use of nucleic acids as
      therapeutic agents, either for the insertion or repair and regulation of specific
      genes. However, the clinical application of these large and charged molecules
      remains highly dependent on the development of delivery systems capable of
      mediating efficient cellular uptake. Since the first observations, two decades
      ago, that some protein-derived domains can translocate across biological
      membranes, a wide group of peptides called cell-penetrating peptides (CPPs) have
      been considered one of the most promising tools to improve non-invasive cellular
      delivery of therapeutic molecules. The mechanistic basis of CPP and CPP conjugate
      cellular uptake remains controversial. However, biophysical studies on the
      interactions of CPPs with membrane models have contributed to unravel the
      mechanisms underlying CPP membrane translocation as well as to propose
      relationships between those mechanisms and CPP efficiency in mediating cargo
      delivery. In this review, representative examples of CPPs were gathered from the
      most recent literature in order to emphasize the contributions of chemists,
      biophysicists and cell biologists towards the rational design of increasingly
      more efficient delivery systems. In this context, the present review aims at
      giving an overview of some of the most significant CPP families and their
      biological applications as nucleic acid delivery systems.

PMID- 23140454
TI  - Cell penetrating peptide delivery of splice directing oligonucleotides as a
      treatment for Duchenne muscular dystrophy.
AB  - Duchenne muscular dystrophy is a severe, X-linked muscle wasting disorder caused
      by the absence of an integral structural protein called dystrophin. This is
      caused by mutations or deletions in the dystrophin gene which disrupt the reading
      frame, thereby halting the production of a functional protein. A number of
      potential therapies have been investigated for the treatment of this disease
      including utrophin upregulation, 'stop-codon read through' aminoglycosides and
      adeno-associated virus gene replacement as well as stem cell therapy. However,
      the most promising treatment to date is the use of antisense oligonucleotides
      which cause exon skipping by binding to a specific mRNA sequence, skipping the
      desired exon, thereby restoring the reading frame and producing a truncated yet
      functional protein. The results from recent 2'OMePS and morpholino clinical
      trials have renewed hope for Duchenne patients; however in vivo studies in a
      mouse model, mdx, have revealed low systemic distribution and poor delivery of
      oligonucleotides to affected tissues such as the brain and heart. However a
      variety of cell penetrating peptides directly conjugated to antisense
      oligonucleotides have been shown to enhance delivery in Duchenne model systems
      with improved systemic distribution and greater efficacy compared to 'naked'
      antisense oligonucleotides. These cell penetrating peptides, combined with an
      optimised dose and dosing regimen, as well as thorough toxicity profile have the
      potential to be developed into a promising treatment which may be progressed to
      clinical trial.

PMID- 23140455
TI  - Intracellular fate of peptide-mediated delivered cargoes.
AB  - Cell-penetrating peptides (CPPs) are promising tools for intracellular delivery.
      However, no consensus regarding their internalization mechanism has been reached
      within the scientific community. Although endocytosis seems to be the preferred
      internalization mechanism for most CPP-cargo complexes, examples of direct
      translocation have also been identified. In this review we go through the several
      ways of studying CPP-mediated cargo delivery in cells and the possible factors
      affecting the internalization pathways followed by these complexes. In addition,
      we analyze the CPP-mediated delivery of two relevant cargoes, namely quantum dots
      and nucleic acids, focusing on the internalization mechanism that they follow.

PMID- 23140456
TI  - In vivo delivery of morpholino oligos by cell-penetrating peptides.
AB  - Morpholino oligos (Morpholinos) are widely used tools for knocking down gene
      expression and are currently in a clinical trial for treatment of Duchene
      muscular dystrophy. A Morpholino analog has been in a clinical trial as a
      potential anti-bioterrorism agent for inhibiting replication of deadly Marburg
      viral infection. The cellular uptake of Morpholinos can been greatly increased by
      conjugation with cell-penetrating peptides (CPP). The use of the CPP-Morpholino
      conjugates (PPMOs) in vivo has been broadly demonstrated in viral, bacterial,
      genetic and other diseases. The following aspects of PPMOs will be discussed in
      this paper including chemistry, stability, antisense specificity, mechanism of
      cellular uptake, in vivo efficacy, tissue distribution, pharmacokinetics,
      toxicity and the human clinical trials. PPMOs are powerful research tools for
      studying gene function in animals and their properties are being improved as
      potential human therapeutic agents.

PMID- 23140457
TI  - CPP-conjugated anti-apoptotic peptides as therapeutic tools of ischemia
      reperfusion injuries.
AB  - Acute myocardial infarction (AMI) is a frequent and disabling disease, which is
      the first cause of cardiovascular mortality worldwide. Infarct size is a major
      determinant of myocardial functional recovery and mortality after AMI. Limitation
      of infarct size thus appears as an appropriate strategy to prevent post-ischemic
      heart failure and improve survival. Reperfusion is the only treatment recommended
      to reduce infarct size but despite obvious benefits, it may also have deleterious
      effects called ischemia-reperfusion (IR) injury including myocyte cell death.
      Proteins involved in the apoptosis cascade generally interact over large surfaces
      lacking well-defined pockets. Therefore, inhibitory peptides are optimal
      biomolecules to target these large protein surfaces, they are often more
      selective to their target than conventional small organic molecules, and they can
      be tailored for optimal affinity or desired metabolic property. Since peptides do
      not cross freely biological membranes, they are generally administered in
      association with cell penetrating peptides (CPPs) and with homing peptides (HPs)
      for selective organs or tissues targeting. As a first approach in vivo, we made
      use of the already known BH4 peptidic inhibitor of the mitochondrial apoptotic
      pathway, which showed cardioprotective properties in a murine model of AMI after
      a single bolus of intravenous administration. More importantly, similar peptidic
      strategies and tools are likely to be adaptable to many other situations in which
      cells have to be protected from apoptosis such as stroke or organ
      transplantation.

PMID- 23140458
TI  - Homeoproteins and homeoprotein-derived peptides: going in and out.
AB  - Since the initial evidence that antennapedia homeobox can cross cell membranes
      and internalize into cells, numerous peptides with similar translocation
      properties have been described. These peptides are referred to as cell
      penetrating peptides (CPPs) or protein-transduction domains (PTDs). Reviews on
      reported CPP sequences have been recently published, together with reviews on
      their mechanisms of internalization. In this review, we will focus on natural
      homeoproteins and homeoprotein-derived peptides and describe results that have
      been obtained among different laboratories to unravel the different pathways by
      which these molecules reach the cell cytosol and nucleus or transfer from one
      cell to another. Using homeoproteins as a paradigm, we will also summarize recent
      evidences of the physiological functions of endogenous protein translocation.

PMID- 23140459
TI  - Arginine-rich peptides: methods of translocation through biological membranes.
AB  - Intracellular delivery using cell-penetrating peptides (CPPs) has received
      considerable attention as a promising method for introducing exogenous molecules
      into cells. The mechanisms that enable efficient internalization of CPPs together
      with cargo molecules are also of interest. In this review, we describe our
      current views of membrane translocation of CPPs, especially those rich in
      arginine, as these peptides represent one of the most frequently employed classes
      of CPPs.

PMID- 23140460
TI  - PTD/CPP peptide-mediated delivery of siRNAs.
AB  - siRNA-induced RNA Interference (RNAi) responses have great potential to treat
      human disease; however, siRNAs are highly charged macromolecules with no ability
      to enter cells and require a delivery agent. Peptide Transduction Domains (PTDs),
      also called Cell Penetrating Peptides (CPPs), are delivery peptides with the
      potential to deliver macromolecular peptides, proteins and siRNAs into cells.
      Here we discuss the multitude of ways that PTDs/CPPs have been utilized to
      deliver siRNAs from direct conjugates to complex nanoparticles. PTD/CPP-mediated
      siRNA delivery has come a long way and has great potential to address the siRNA
      delivery problem.

PMID- 23140461
TI  - Editorial: Cell penetrating peptides as delivery vectors for biomolecules.

PMID- 23140462
TI  - Tris(carbene)borate ligands featuring imidazole-2-ylidene, benzimidazol-2
      ylidene, and 1,3,4-triazol-2-ylidene donors. Evaluation of donor properties in
      four-coordinate {NiNO}10 complexes.
AB  - The synthesis and characterization of new tris(carbene)borate ligand precursors
      containing substituted benzimidazol-2-ylidene and 1,3,4-triazol-2-ylidene donor
      groups, as well as a new tris(imidazol-2-ylidene)borate ligand precursor are
      reported. The relative donor strengths of the tris(carbene)borate ligands have
      been evaluated by the position of nu(NO) in four-coordinate {NiNO}(10) complexes,
      and follow the order: imidazol-2-ylidene > benzimidazol-2-ylidene > 1,3,4-triazol
      2-ylidene. There is a large variation in nu(NO), suggesting these ligands to have
      a wide range of donor strengths while maintaining a consistent ligand topology.
      All ligands are stronger donors than Tp* and Cp*.

PMID- 23140463
TI  - False positives on both dexamethasone testing and urinary free cortisol in women
      on oral contraception: dose-response effects.

PMID- 23140464
TI  - Long-term neurocognitive effects of methylphenidate in patients with attention
      deficit hyperactivity disorder, even at drug-free status.
AB  - BACKGROUND: Methylphenidate (MPH), a psycho-stimulant, is the most widely
      administered drug for the pharmacological management of patients with attention
      deficit hyperactivity disorder (ADHD). This study attempts to determine whether
      sustainable improvements occur in neurocognitive function among ADHD patients
      following 12-month treatment with MPH, at drug-free status. Whether age groups,
      gender or ADHD subtypes differ in neurocognitive performance during MPH treatment
      is also examined. METHODS: Study participants consisted of 103 ADHD patients
      (mean age: 9.1 +/- 1.9 years old) who were drug naive or drug free for at least 6
      months. The patients were prescribed oral short-acting MPH at each dose range of
      0.3-1.0 mg/kg daily. During 12 months of the study, the patients underwent the
      test of variables of attention (TOVA) at the baseline, month 6 and month12.
      Patients were instructed to not intake MPH for one week before the second and the
      third TOVA. RESULTS: Seventy five patients completed the study. Results of this
      study indicated that although commission errors and response sensitivity (d')
      significantly improved during MPH treatment for 12 months, omission errors,
      response time, response time variability and ADHD score did not. While younger
      ADHD patients (<9 y/o) performed better in response time, response time
      variability, d' and ADHD score than older ones (>=9 y/o), the latter more
      significantly improved in response time than the former during 12 months of
      treatment. Additionally, boys improved more than girls in omission error and d'.
      Moreover, although ADHD subtypes significantly differed in ADHD score during the
      treatment, MPH treatment and ADHD subtypes did not interact with each other for
      all TOVA indices. CONCLUSIONS: ADHD patients significantly improved in
      impulsivity and perceptual sensitivity, determined as TOVA, during MPH treatment
      for 12 months. Age and gender, yet not ADHD subtypes, appear to influence the MPH
      treatment effects in some indices of TOVA. A future study containing a comparison
      group is suggested to confirm whether the neurocognitive improvements are
      attributed to long-term effects of MPH or natural maturation of patients.

PMID- 23140465
TI  - Reported heterosexual intercourse and related behaviours among primary school
      pupils in Kinondoni district, Dar es Salaam, Tanzania.
AB  - A cross-sectional questionnaire survey was conducted among 2820 pupils in 22
      randomly selected primary schools in Kinondoni district, Tanzania. The objective
      was to identify the proportion of pupils who reported ever having had sexual
      intercourse, as well as sociodemographic and psychosocial factors and other
      sexual-related behaviours associated with heterosexual intercourse among pupils.
      About 13% (376) of participating pupils reported having had heterosexual
      intercourse. The proportion of pupils who reported doing so varied significantly
      by age, sex, school grade and parents' education. Regarding psychosocial factors,
      pupils who agreed that having sexual intercourse implies love for a partner and
      that sexual intercourse creates peer approval were significantly more likely to
      report having had heterosexual intercourse. Pupils who reported having a girl/boy
      friend, kissed a boy/girl, engaged in light petting, engaged in heavy petting or
      practised oral sex and anal sex were more likely to report ever having
      heterosexual intercourse. The implications for programme and intervention
      development are discussed.

PMID- 23140467
TI  - Modelling the hare and the tortoise: predicting the range of in-vehicle task
      times using critical path analysis.
AB  - Analytic models can enable predictions about important aspects of the usability
      of in-vehicle information systems (IVIS) to be made at an early stage of the
      product development process. Task times provide a quantitative measure of user
      performance and are therefore important in the evaluation of IVIS usability. In
      this study, critical path analysis (CPA) was used to model IVIS task times in a
      stationary vehicle, and the technique was extended to produce predictions for
      slowperson and fastperson performance, as well as average user (middleperson)
      performance. The CPA-predicted task times were compared to task times recorded in
      an empirical simulator study of IVIS interaction, and the predicted times were,
      on average, within acceptable precision limits. This work forms the foundation
      for extension of the CPA model to predict IVIS task times in a moving vehicle, to
      reflect the demands of the dual-task driving scenario. PRACTITIONER SUMMARY: The
      CPA method was extended for the prediction of slowperson and fastperson IVIS task
      times. Comparison of the model predictions with empirical data demonstrated
      acceptable precision. The CPA model can be used in early IVIS evaluation;
      however, there is a need to extend it to represent the dual-task driving
      scenario.

PMID- 23140468
TI  - Does size matter? Thoughts about insulin pen needles.

PMID- 23140466
TI  - Regression of schwannomas induced by adeno-associated virus-mediated delivery of
      caspase-1.
AB  - Schwannomas are tumors formed by proliferation of dedifferentiated Schwann cells.
      Patients with neurofibromatosis 2 (NF2) and schwannomatosis develop multiple
      schwannomas in peripheral and cranial nerves. Although benign, these tumors can
      cause extreme pain and compromise sensory/motor functions, including hearing and
      vision. At present, surgical resection is the main treatment modality, but it can
      be problematic because of tumor inaccessibility and risk of nerve damage. We have
      explored gene therapy for schwannomas, using a model in which immortalized human
      NF2 schwannoma cells expressing a fluorescent protein and luciferase are
      implanted in the sciatic nerve of nude mice. Direct injection of an adeno
      associated virus (AAV) serotype 1 vector encoding caspase-1 (ICE) under the
      Schwann-cell specific promoter, P0, leads to regression of these tumors with
      essentially no vector-mediated neuropathology, and no changes in sensory or motor
      function. In a related NF2 xenograft model designed to cause measurable pain
      behavior, the same gene therapy leads to tumor regression and concordant
      resolution of tumor-associated pain. This AAV1-P0-ICE vector holds promise for
      clinical treatment of schwannomas by direct intratumoral injection to achieve
      reduction in tumor size and normalization of neuronal function.

PMID- 23140469
TI  - Ventricular fibrillation induced by spontaneous hypothermia in a patient with
      early repolarization syndrome.
AB  - INTRODUCTION: The early repolarization (ER) pattern on ECG was originally
      described in the context of hypothermia. CASE SUMMARY: We present the case of a
      34-year-old male with cardiac arrest in the context of spontaneous hypothalamic
      mediated thermal dysregulation after intracranial hemorrhage. Ventricular
      fibrillation with a marked ER pattern recurred with therapeutic hypothermia.
      Spontaneous hypothermia due to hypothalamic dysregulation was observed to enhance
      the amplitude of the ER pattern and was contemporaneous with recurrent
      ventricular fibrillation during follow-up. CONCLUSIONS: Hypothermia is an
      important trigger of VF in the setting of early repolarization syndrome, and
      warrants assessment as an environmental trigger of spontaneous events.

PMID- 23140470
TI  - Alteration in lipoprotein-associated phospholipase A2 levels during acute
      coronary syndrome and its relationship to standard biomarkers.
AB  - BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) probably plays an
      important role in the development of acute coronary syndrome (ACS); elevated
      levels of Lp-PLA2 are associated with a poorer prognosis in patients with
      ischemic heart disease. Alterations of Lp-PLA2 levels during ACS and its
      relationship to standard biomarkers are, however, unclear. FINDINGS: Fifty-one
      consecutive ACS patients were enrolled in the study. All were managed with early
      invasive strategy and according to the current guidelines for pharmacotherapy;
      intensive statin therapy was started in all patients at admission. Serum levels
      of Lp-PLA2, LDL-cholesterol (LDL), troponin l (Tnl), and C-reactive protein (CRP)
      were assessed at admission (D0), on the first morning (D1), and on the second
      morning of hospitalization (D2). Mean serum levels of Lp-PLA2 (ng/mL) decreased
      from 264.6+/-19.1 at D0, to 193.2+/-14.4 at D1 (P < 0.001 vs. D0) and 189.8+/
      22.6 at D2 (P = 0.002 vs. D0; P = not significant vs. D1). Alterations in Lp-PLA2
      levels significantly correlated with changes in LDL (r = 0.43; P = 0.008). On the
      other hand, no relationship between Lp-PLA2 and Tnl or CRP was found.
      CONCLUSIONS: Initially, serum levels of Lp-PLA2 were significantly elevated in
      ACS patients, but decreased within the first 24 hours after admission and
      subsequently remained stable. Lp-PLA2 levels correlated with LDL levels but not
      with Tnl or CRP levels. Our results demonstrated dynamic alterations in Lp-PLA2
      levels during the early stages of ACS and, therefore, indirectly support the
      hypothesis of an active role for Lp-PLA2 in the pathogenesis of ACS.

PMID- 23140474
TI  - Probiotics do not significantly reduce nosocomial pneumonia.

PMID- 23140471
TI  - Effective inter-residue contact definitions for accurate protein fold
      recognition.
AB  - BACKGROUND: Effective encoding of residue contact information is crucial for
      protein structure prediction since it has a unique role to capture long-range
      residue interactions compared to other commonly used scoring terms. The residue
      contact information can be incorporated in structure prediction in several
      different ways: It can be incorporated as statistical potentials or it can be
      also used as constraints in ab initio structure prediction. To seek the most
      effective definition of residue contacts for template-based protein structure
      prediction, we evaluated 45 different contact definitions, varying bases of
      contacts and distance cutoffs, in terms of their ability to identify proteins of
      the same fold. RESULTS: We found that overall the residue contact pattern can
      distinguish protein folds best when contacts are defined for residue pairs whose
      Cbeta atoms are at 7.0 A or closer to each other. Lower fold recognition accuracy
      was observed when inaccurate threading alignments were used to identify common
      residue contacts between protein pairs. In the case of threading, alignment
      accuracy strongly influences the fraction of common contacts identified among
      proteins of the same fold, which eventually affects the fold recognition
      accuracy. The largest deterioration of the fold recognition was observed for beta
      class proteins when the threading methods were used because the average alignment
      accuracy was worst for this fold class. When results of fold recognition were
      examined for individual proteins, we found that the effective contact definition
      depends on the fold of the proteins. A larger distance cutoff is often
      advantageous for capturing spatial arrangement of the secondary structures which
      are not physically in contact. For capturing contacts between neighboring beta
      strands, considering the distance between Calpha atoms is better than the Cbeta
      based distance because the side-chain of interacting residues on beta strands
      sometimes point to opposite directions. CONCLUSION: Residue contacts defined by
      Cbeta-Cbeta distance of 7.0 A work best overall among tested to identify proteins
      of the same fold. We also found that effective contact definitions differ from
      fold to fold, suggesting that using different residue contact definition specific
      for each template will lead to improvement of the performance of threading.

PMID- 23140473
TI  - Mechanical factors play an important role in pectus excavatum with thoracic
      scoliosis.
AB  - BACKGROUND: This study investigated the incidence, imaging characteristics and
      mechanical factors in scoliotic patients with pectus excavatum. METHODS: A total
      of 142 scoliostic patients with pectus excavatum were evaluated prior to
      operation. The evaluation included a complete physical exam, phenotype and
      severity of the pectus excavatum, incidence and severity of scoliosis, and
      analysis of radiological images, including calculation of the Haller index.
      RESULTS: Twenty five out of 142 patients (17.61%) with pectus excavatum had
      scoliosis with a Cobb angle >10 degrees, and in 80.00% of the cases the spinal
      column was bent to the right. Seventeen patients had bent-to-the-right spines
      that involved the 6th to 10 th thoracic vertebrae. We found that 23 out of 25
      patients with a Cobb angle more than 10 degrees  were teenagers and adults. The
      incidence of scoliosis was only 6.06% in the children under 11 years whereas it
      was 21.79% in the teenage group. CONCLUSIONS: Mechanical forces appear to play a
      role in the coexistence of pectus excavatum and scoliosis. There is a
      relationship between age, severity (Haller index), asymmetry and scoliosis. The
      heart and mediastinum play a role in providing an outward force to the left of
      the sternum which may be an important reason for the coexistence of pectus
      excavatum and scoliosis, but the correlation needs further proof.

PMID- 23140475
TI  - Sequence defined disulfide-linked shuttle for strongly enhanced intracellular
      protein delivery.
AB  - Intracellular protein transduction technology is opening the door for a promising
      alternative to gene therapy. Techniques have to address all critical steps, like
      efficient cell uptake, endolysosomal escape, low toxicity, while maintaining full
      functional activity of the delivered protein. Here, we present the use of a
      chemically precise, structure defined three-arm cationic oligomer carrier
      molecule for protein delivery. This carrier of exact and low molecular weight
      combines good cellular uptake with efficient endosomal escape and low toxicity.
      The protein cargo is covalently attached by a bioreversible disulfide linkage.
      Murine 3T3 fibroblasts could be transduced very efficiently with cargo nlsEGFP,
      which was tagged with a nuclear localization signal. We could show subcellular
      delivery of the nlsEGFP to the nucleus, confirming cytosolic delivery and
      expected subsequent subcellular trafficking. Transfection efficiency was
      concentration-dependent in a directly linear mode and 20-fold higher in
      comparison with HIV-TAT-nlsEGFP containing a functional TAT transduction domain.
      Furthermore, beta-galactosidase as a model enzyme cargo, modified with the
      carrier oligomer, was transduced into neuroblastoma cells in enzymatically active
      form. 

PMID- 23140476
TI  - Improving information recognition and performance of recycling chimneys.
AB  - The aim of this study was to assess and improve how recyclers (individuals
      carrying out the task of recycling) make use of visual cues to carryout recycling
      tasks in relation to 'recycling chimneys' (repositories for recycled waste). An
      initial task analysis was conducted through an activity sampling study and an eye
      tracking experiment using a mobile eye tracker to capture fixations of recyclers
      during recycling tasks. Following data collection using the eye tracker, a set of
      recommendations for improving information representation were then identified
      using the widely researched skills, rules, knowledge framework, and for a
      comparative study to assess the performance of improved interfaces for recycling
      chimneys based on Ecological Interface Design principles. PRACTITIONER SUMMARY:
      Information representation on recycling chimneys determines how we recycle waste.
      This study describes an eco-ergonomics-based approach to improve the design of
      interfaces for recycling chimneys. The results are valuable for improving the
      performance of waste collection processes in terms of minimising contamination
      and increasing the quantity of recyclables.

PMID- 23140477
TI  - Application of Tb(4)O(7) nanoparticles for lasalocid and salicylate determination
      in food analysis.
AB  - The usefulness of Tb(4)O(7) nanoparticles (NPs) as analytical reagents using
      sensitized luminescence as a detection system is described for the first time,
      and the results obtained are compared with those obtained using Tb(III) ions. Two
      drugs used in veterinary practice, namely, lasalocid (LAS) and salicylate (SAL),
      have been chosen as model analytes to carry out this study. The experimental
      conditions for these systems have been optimized, and their analytical features
      were obtained. The detection limits obtained for LAS and SAL using Tb(4)O(7) NPs
      were 1.0 and 4.0 ng mL(-1), respectively, which were comparable to those obtained
      using Tb(III) ions: 1.8 and 1.0 ng mL(-1), respectively. However, precision data,
      with relative standard deviation values in the range 2.3-3.8% using the NPs and
      3.5-6.5% using Tb(III) ions, were slightly better for LAS with Tb(4)O(7) NPs. The
      practical analytical usefulness of Tb(4)O(7) NPs as luminescent reagents has been
      shown by performing the determination of LAS in tap water, feed premix, and egg
      samples, obtaining recoveries in the range of 80.0-105.0%.

PMID- 23140479
TI  - Perceptual strength is different from sensorimotor strength: evidence from the
      centre-periphery asymmetry in masked priming.
AB  - Near-threshold prime stimuli can facilitate or hinder responses to target
      stimuli, creating either a positive compatibility effect (PCE) or a negative
      compatibility effect (NCE). An asymmetry has been reported between primes
      presented in near periphery, which produced a PCE, and foveal primes, which
      produced an NCE under comparable conditions. This asymmetry has been attributed
      to the difference in retinal sensitivity, but it remains unclear whether this
      means that equating discrimination performance for primes in fovea and periphery,
      in order to account for differences in perceptual sensitivity, would make the
      priming effects the same. Wider work indicates that perceptual ability can
      dissociate from visuomotor effects, predicting that equating perceptual ability
      for fovea and periphery would not equate priming. We tested these opposite
      possibilities by matching discrimination performance for masked Gabor patches in
      fovea and near periphery (6 degrees ) and using these as primes in a masked
      priming paradigm expected to elicit NCEs. We found the asymmetry remained: NCE
      for fovea and PCE for periphery. We replicated this with both blocked and
      randomized procedures to check for attentional effects. We conclude that equating
      perceptual strength (discriminability) of stimuli does not equate their
      sensorimotor impact due to differences in the relative importance of different
      visual pathways and differing temporal dynamics in perceptual and sensorimotor
      processes.

PMID- 23140478
TI  - Warifteine, a bisbenzylisoquinoline alkaloid, induces relaxation by activating
      potassium channels in vascular myocytes.
AB  - The present study used functional and electrophysiological approaches to
      investigate the mechanisms by which warifteine, a bisbenzylisoquinoline alkaloid
      isolated from Cissampelos sympodialis Eichl., causes vasorelaxation of the rat
      thoracic aorta. Warifteine (1 pmol/L-10 MUmol/L) induced concentration-dependent
      relaxation (pD(2) = 9.40 +/- 0.06; n = 5) of endothelium-intact aortic rings
      precontracted with noradrenaline (10-100 MUmol/L). The relaxation effects were
      not attenuated by removal of the endothelium. Warifteine also induced the
      relaxation of prostaglandin F(2alpha) (1-10 mmol/L)-precontracted rings (pD(2) =
      9.2 +/- 0.2; n = 8). In contrast, the relaxant activity of warifteine was nearly
      abolished in high K(+) (80 mmol/L)-precontracted aortic rings. In preparations
      incubated with 20 mmol/L KCl or with the K(+) channel blockers tetraethylammonium
      (1, 3 and 5 mmol/L), iberiotoxin (20 nmol/L), 4-aminopyridine (1 mmol/L) or
      glibenclamide (10 MUmol/L), the vasorelaxant activity of warifteine was markedly
      reduced. However, BaCl(2) (1 mmol/L) had no effect on the relaxant effects of
      warifteine. In vascular myocytes, warifteine (100 nmol/L) significantly increased
      whole-cell K(+) currents (at 70 mV). Under nominally Ca(2+) -free conditions,
      warifteine did not reduce extracellular Ca(2+) -induced contractions in rings
      precontracted with high K(+) or noradrenaline (100 MUmol/L). Together, the
      results of the present study indicate that warifteine induces potent
      concentration-dependent relaxation in the rat aorta via an endothelium
      independent mechanism that involves the activation of K(+) channels.

PMID- 23140480
TI  - The Relaxation Exercise and Social Support Trial (RESST): a community-based
      randomized controlled trial to alleviate medically unexplained vaginal discharge
      symptoms.
AB  - BACKGROUND: Symptoms such as medically unexplained vaginal discharge (MUVD) are
      common and bothersome, leading to potentially unnecessary use of resources.
      METHODS: A community-based individually randomized controlled trial to assess the
      effectiveness of a relatively simple, culturally appropriate multi-component
      intervention on reducing reported MUVD, among women suffering from low-moderate
      levels of common mental distress. The setting was a socio-economically deprived,
      informal settlement in the southern suburbs of Beirut, Lebanon. The intervention
      comprised up to 12 group sessions implemented over a six-week period, each
      divided into a psychosocial and a relaxation exercise component. The primary
      outcome was self-reported MUVD, which was defined as a complaint of vaginal
      discharge upon ruling out reproductive tract infections (RTIs), through lab
      analysis. Anxiety and/or depression symptoms were the secondary outcomes for this
      trial. These were assessed using an Arabic validated version of the Hopkins
      Symptoms Checklist-25 (HSCL-25). Assessments were done at baseline and six months
      using face-to face interviews, pelvic examinations and laboratory tests. Women
      were randomized into either intervention or control group. Blinding on the
      intervention status was not possible for both logistic and ethical reasons,
      especially as knowledge of involvement in the intervention was integral to its
      delivery. Intent to treat analysis was used. RESULTS: Of 75 women randomized to
      the intervention, 48% reported MUVD at 6 months compared with 63% of 73 in the
      control group (difference of -15%, 95% confidence interval (CI) -31%, 0%,
      p=0.067). Adjustments for baseline imbalances and any factors relating to consent
      had no appreciable effect on these results. The risk of MUVD was reduced in
      absolute terms by 2.4% for each intervention session attended (95% CI -4.9%,
      0.0%, p=0.049). While there was also marginal evidence of a beneficial effect on
      anxiety, there was no evidence of mediation of the effect on MUVD through
      measures of common mental disorders. CONCLUSION: This study confirms that MUVD is
      an important public health problem. While the benefits of this intervention may
      appear modest, the intervention offers an opportunity for women to enhance their
      problem-solving skills as well as use physical relaxation techniques that can
      help them deal with stressful in their lives. Further research is needed in a
      variety of contexts, for different populations and preferably involving larger
      randomized trials of such an intervention. TRIAL REGISTRATION: * Title of trial:
      The Relaxation Exercise and Social Support Trial ISRCTN assigned: ISRCTN98441241
      Date of assignation: 10/09/2010 Link: http://www.controlled
      trials.com/ISRCTN98441241* Also registered at the Wellcome Trust
      register:http://www.controlled-trials.com/mrct/trial/469943/98441241.

PMID- 23140482
TI  - Stereoselective total synthesis of FD-891.
AB  - FD-891, a structurally unique 16-membered macrolide having anticancer activity,
      was synthesized according to a strategy employing asymmetric allylation, Prins
      cyclization, cross-metathesis reaction, Yamaguchi lactonization, and Julia
      Kocienski olefination.

PMID- 23140481
TI  - Histone deacetylase inhibition activates transgene expression from integration
      defective lentiviral vectors in dividing and non-dividing cells.
AB  - Integration-defective lentiviral vectors (IDLVs) are being increasingly deployed
      in both basic and preclinical gene transfer settings. Often, however, the IDLV
      transgene expression profile is muted when compared to that of their integration
      proficient counterparts. We hypothesized that the episomal nature of IDLVs turns
      them into preferential targets for epigenetic silencing involving chromatin
      remodeling histone deacetylation. Therefore, vectors carrying an array of cis
      acting elements and transcriptional unit components were assembled with the aid
      of packaging constructs encoding either the wild-type or the class I mutant D116N
      integrase moieties. The transduction levels and transgene-product yields provided
      by each vector class were assessed in the presence and absence of the histone
      deacetylase (HDAC) inhibitors sodium butyrate and trichostatin A. To investigate
      the role of the target cell replication status, we performed experiments in
      growth-arrested human mesenchymal stem cells and in post-mitotic syncytial
      myotubes. We found that IDLVs are acutely affected by HDACs regardless of their
      genetic makeup or target cell replication rate. Interestingly, the magnitude of
      IDLV transgene expression rescue due to HDAC inhibition varied in a vector
      backbone- and cell type-dependent manner. Finally, investigation of histone
      modifications by chromatin immunoprecipitation followed by quantitative PCR (ChIP
      qPCR) revealed a paucity of euchromatin marks distributed along IDLV genomes when
      compared to those measured on isogenic integration-competent vector templates.
      These findings support the view that IDLVs constitute preferential targets for
      epigenetic silencing involving histone deacetylation, which contributes to
      dampening their full transcriptional potential. Our data provide leads on how to
      most optimally titrate and deploy these promising episomal gene delivery
      vehicles.

PMID- 23140483
TI  - Evaluation of metric, topological, and temporal ordering memory tasks after
      lateral fluid percussion injury.
AB  - Impairments in learning and memory occur in as many as 50% of patients following
      traumatic brain injury (TBI). Similar impairments occur in rodent models of TBI,
      and the development of new memory testing procedures provides an opportunity to
      examine how TBI affects memory processing in specific neural memory systems.
      Specifically, metric, topological, and temporal ordering tasks are object-based
      tests for memory of spatial orientation and temporal sequencing working memory
      developed for use in rodents. Previous studies demonstrated that specific lesions
      of the dentate gyrus/CA3 of the hippocampus and the parietal cortex resulted in
      deficits in the metric and topological spatial orientation tasks, respectively.
      Lesions of the CA1 impaired a rat's ability to recall the temporal order of
      odors. The purpose of the following study was to determine whether moderate
      lateral fluid percussion TBI would generate deficits in these working memory
      tasks, and whether observed deficits were associated with cell loss in the CA2/3
      and/or CA1 of the hippocampus. Two weeks following a moderate lateral fluid
      percussion TBI, adult rats demonstrated significant deficits in both the metric
      and temporal ordering tasks (p<0.05) but not in the topological task.
      Stereological analysis identified a significant reduction in neurons in the CA2/3
      (p<0.05) but not the CA1 of the hippocampus. These data demonstrate the utility
      of three object-based tasks to expand our understanding of how different neural
      memory systems are affected by TBI.

PMID- 23140484
TI  - Sexual health of Latino migrant day labourers under conditions of structural
      vulnerability.
AB  - The purpose of this paper is to explore the context of the sexual health of
      Latino migrant day labourers in the USA, challenges to sexual health and ways of
      coping, with attention to conditions of structural vulnerability permeating the
      lives of this unique Latino population. Given the limited information about this
      topic and population, ethnographic research employing in-depth semi-structured
      interviews with 51 labourers, recruited through purposive sampling in the San
      Francisco Bay Area, was utilised. The sexual health aspirations of the men are
      deeply embedded in the core value and practice of Latino familismo or, in this
      case, the central goal of securing a family headed by men as providers and
      present husbands/fathers. However, such goals are frequently thwarted by the
      poverty engendering work and prolonged separations from home that characterise
      predominantly undocumented day labour in the USA. Resulting goal frustration,
      combined with pent up sexual urges, often lead to sexual risk in spite of efforts
      to cope with challenges to sexual health. Unless community-, state- and national
      level interventions are developed to mitigate the pronounced structural
      vulnerability of migrant day labourers, individual level interventions to promote
      sexual health, and decrease risk and distress, are likely to have diminishing
      returns.

PMID- 23140485
TI  - Long-term results of transcatheter atrial fibrillation ablation in patients with
      impaired left ventricular systolic function.
AB  - INTRODUCTION: Long-term outcome of AF ablation in patients with impaired LVEF is
      unknown. The aim of this study is to evaluate sinus rhythm (SR) maintenance,
      clinical status, and echocardiographic parameters over a long-term period
      following atrial fibrillation (AF) transcatheter ablation in patients with left
      ventricular ejection fraction (LVEF) <50%. METHODS AND RESULTS: A total of 196
      patients (87.2% males, age 60.5 +/- 10.2 years) with LVEF <50% underwent
      radiofrequency transcatheter ablation for paroxysmal (22.4%) or persistent
      (77.6%) AF. Patients were followed up for 46.2 (16.4-63.5) months regarding AF
      recurrences, functional class, and echocardiographic parameters. All patients
      underwent pulmonary vein isolation, while 167 (85.2%) required additional atrial
      lesions. Eleven (5.6%) patients suffered procedural complications. During follow
      up, 58 (29.6%) patients required repeated ablations. At the follow-up end, 15
      (7.7%) patients died, while 74 (37.8%) documented at least one episode of AF,
      atrial flutter, or atrial ectopic tachycardia. Eighty-three (47.2%) patients
      maintained antiarrhythmic drugs. During follow-up, NYHA class improved by at
      least one class more frequently among patients maintaining SR compared to those
      experiencing relapses (70.6% vs 47.9%, P = 0.003). LVEF showed a broader relative
      increase in patients maintaining SR (32.7% vs 21.4%; P = 0.047) and mitral
      regurgitation grading significantly decreased (P <0.001) only within these
      patients. At multivariable analysis SR maintenance emerged as an independent
      predictor (odds ratio 4.26, 95% CI 1.69-10.74, P = 0.002) of long-term clinical
      improvement (reduction in NYHA class >= 1 and relative increase in LVEF >= 10%).
      CONCLUSIONS: Although not substantially worse than in patients with preserved
      LVEF, AF ablation in patients with impaired LVEF is affected by high long-term
      recurrence rate. Among these patients SR maintenance is associated with greater
      clinical improvement.

PMID- 23140486
TI  - The tree alignment problem.
AB  - BACKGROUND: The inference of homologies among DNA sequences, that is, positions
      in multiple genomes that share a common evolutionary origin, is a crucial, yet
      difficult task facing biologists. Its computational counterpart is known as the
      multiple sequence alignment problem. There are various criteria and methods
      available to perform multiple sequence alignments, and among these, the
      minimization of the overall cost of the alignment on a phylogenetic tree is known
      in combinatorial optimization as the Tree Alignment Problem. This problem
      typically occurs as a subproblem of the Generalized Tree Alignment Problem, which
      looks for the tree with the lowest alignment cost among all possible trees. This
      is equivalent to the Maximum Parsimony problem when the input sequences are not
      aligned, that is, when phylogeny and alignments are simultaneously inferred.
      RESULTS: For large data sets, a popular heuristic is Direct Optimization (DO). DO
      provides a good tradeoff between speed, scalability, and competitive scores, and
      is implemented in the computer program POY. All other (competitive) algorithms
      have greater time complexities compared to DO. Here, we introduce and present
      experiments a new algorithm Affine-DO to accommodate the indel (alignment gap)
      models commonly used in phylogenetic analysis of molecular sequence data. Affine
      DO has the same time complexity as DO, but is correctly suited for the affine gap
      edit distance. We demonstrate its performance with more than 330,000 experimental
      tests. These experiments show that the solutions of Affine-DO are close to the
      lower bound inferred from a linear programming solution. Moreover, iterating over
      a solution produced using Affine-DO shows little improvement. CONCLUSIONS: Our
      results show that Affine-DO is likely producing near-optimal solutions, with
      approximations within 10% for sequences with small divergence, and within 30% for
      random sequences, for which Affine-DO produced the worst solutions. The Affine-DO
      algorithm has the necessary scalability and optimality to be a significant
      improvement in the real-world phylogenetic analysis of sequence data.

PMID- 23140488
TI  - Oncolytic reovirus type 3 (Dearing) as a novel therapy in head and neck cancer.
AB  - INTRODUCTION: Locally advanced head and neck cancer carries a poor prognosis,
      even with standard combination (surgery, radiotherapy, chemotherapy) treatment
      regimens. There is a pressing need for novel therapies with activity against this
      tumour type. Oncolytic reovirus type 3 (Dearing) is preferentially cytotoxic in
      tumour cells with an activated Ras signalling pathway and represents a promising
      novel therapy with relevance in head and neck cancer. AREAS COVERED: In this
      review, we discuss the pre-clinical and clinical data that have underpinned the
      translational development of oncolytic reovirus thus far. In particular, we
      describe the iterative nature of the research programme through initial studies
      testing single-agent reovirus therapy and on to subsequent work in which reovirus
      has been combined with either radiotherapy or cytotoxic chemotherapy. We will
      trace the process by which oncolytic reovirus has reached Phase III evaluation in
      combination with carboplatin/paclitaxel in patients with platin-refractory,
      relapsed/metastatic head and neck cancer. EXPERT OPINION: Reovirus is a self
      amplifying, cancer-selective agent that offers huge potential advantages over
      standard chemotherapy, targeted small molecules or monoclonal antibodies.
      However, it is most likely that reovirus will show efficacy and be approved in
      combination with standard modalities (cytotoxic chemotherapy or radiotherapy) or
      other targeted agents, especially those that modulate signal transduction
      pathways. The next 5 years are critical for the development of oncolytic reovirus
      as an anti-cancer therapy and hinge on the ongoing Phase III trial in head and
      neck cancer and other Phase II programmes.

PMID- 23140490
TI  - A question of our marketing or our preconceptions: commentary on the paper 'a
      strategy for human factors/ergonomics: developing the discipline and profession'.
AB  - The present paper is a commentary on the recently published IEA strategy for
      human factors/ergonomics (Dul, J., et al. (2012), A strategy for human
      factors/ergonomics: developing the discipline and profession. Ergonomics, 55(4),
      377-395). Two main issues that demand attention are: (i) the way others
      understand our profession and discipline, and (ii) the way we understand our
      profession and added value to industry. First, it is advocated that the
      discussion on the future of human factors/ergonomics (HFE) should be focused more
      on the quality of the delivered value of HFE and less on its visibility and
      marketing. Second, the three fundamental characteristics of HFE, as proposed in
      the report, are discussed and the consequences of this proposal are further
      developed. Arguments are put forward on the endemic epistemological vagueness
      within the discipline and on the optimistic definition of its aim. Finally, a
      proposal is made at the epistemological level, which challenges some established
      convictions of the discipline. It is advocated that such an epistemological
      evolution may be necessary if HFE is to make progress towards contributing to
      system performance. PRACTITIONER SUMMARY: The paper is a commentary on the IEA
      strategy for human factors/ergonomics. Issues discussed are, the way others
      understand our profession and the way we understand our profession and added
      value to industry. Some of the established convictions of the discipline are
      challenged and proposals are made to overcome these.

PMID- 23140489
TI  - Gene expression profiling of macrophages: implications for an immunosuppressive
      effect of dissolucytotic gold ions.
AB  - BACKGROUND: Gold salts has previously been used in the treatment of rheumatoid
      arthritis but have been replaced by biologicals such as TNF-alpha inhibitors. The
      mechanisms behind the anti-inflammatory effect of metallic gold ions are still
      unknown, however, recent data showed that charged gold atoms are released from
      pure metallic gold implants by macrophages via a dissolucytosis membrane, and
      that gold ions are taken up by local macrophages, mast cells and to some extent
      fibroblasts. These findings open the question of possible immunomodulatory
      effects of metallic gold and motivate efforts on a deeper understanding of the
      effect of metallic gold on key inflammatory cells as macrophages. METHODS: Human
      macrophage cells (cell line THP-1) were grown on gold foils and intracellular
      uptake was analysed by autometallography. The impact of phagocytised gold ions on
      viability of THP-1 cells was investigated by trypan blue staining and TUNEL
      assay. The global gene expression profile of THP-1 cells after incorporation of
      gold ions was studied using microarray analysis comprising approximately 20,000
      genes. The gene expression data was confirmed by measurement of secreted
      proteins. RESULTS: Autometallography showed intracellular uptake of gold ions
      into THP-1 cells. No significant effect on viability of THP-1 cells was
      demonstrated. Our data revealed a unique gene expression signature of
      dissolucytotic THP-1 cells that had taken up gold ions. A large number of
      regulated genes were functionally related to immunomodulation. Gold ion uptake
      induced downregulation of genes involved in rheumatoid arthritis such as
      hepatocyte growth factor, tenascin-C, inhibitor of DNA binding 1 and 3 and matrix
      metalloproteinase 13. CONCLUSION: The data obtained in this study offer new
      insights into the mode of action of gold ions and suggest for the investigation
      of effects on other key cells and a possible future role of metallic gold as
      implants in rheumatoid arthritis or other inflammatory conditions.

PMID- 23140491
TI  - Response to the commentary 'A question of our marketing or our preconceptions'.

PMID- 23140498
TI  - Probiotics: an obedient ally or an insidious enemy?

PMID- 23140497
TI  - Mechanisms underpinning effective peer support: a qualitative analysis of
      interactions between expert peers and patients newly-diagnosed with bipolar
      disorder.
AB  - BACKGROUND: The increasing burden on mental health services has led to the
      growing use of peer support in psychological interventions. Four theoretical
      mechanisms have been proposed to underpin effective peer support: advice grounded
      in experiential knowledge, social support, social comparison and the helper
      therapy principle. However, there has been a lack of studies examining whether
      these mechanisms are also evident in clinical populations in which interpersonal
      dysfunction is common, such as bipolar disorder. METHOD: This qualitative study,
      conducted alongside a randomized controlled trial, examined whether the four
      mechanisms proposed to underpin effective peer support were expressed in the
      email exchange between 44 individuals newly-diagnosed with bipolar disorder and
      their Informed Supporters (n = 4), over the course of a supported online
      psychoeducation program for bipolar disorder. A total of 104 text segments were
      extracted and coded. The data were complemented by face-to-face interviews with
      three of the four Informed Supporters who participated in the study. RESULTS:
      Qualitative analyses of the email interchange and interview transcripts revealed
      rich examples of all four mechanisms. The data illustrated how the involvement of
      Informed Supporters resulted in numerous benefits for the newly-diagnosed
      individuals, including the provision of practical strategies for illness
      management as well as emotional support throughout the intervention. The Informed
      Supporters encouraged the development of positive relationships with mental
      health services, and acted as role models for treatment adherence. The Informed
      Supporters themselves reported gaining a number of benefits from helping,
      including a greater sense of connectedness with the mental health system, as well
      as a broader knowledge of illness management strategies. CONCLUSIONS: Examples of
      the mechanisms underpinning effective peer support were found in the sample of
      emails from individuals with newly-diagnosed bipolar disorder and their Informed
      Supporters. Experiential knowledge, social support, social comparison and helper
      therapy were apparent, even within a clinical population for whom relationship
      difficulties are common. Trial registration number ACTRN12608000411347.

PMID- 23140499
TI  - Diversity of phenolic profiles in the fruit skin of Prunus domestica plums and
      related species.
AB  - The fruits of the European plum  Prunus domestica  exhibit a great diversity in
      appearance including skin colors. This study attempts to elucidate the
      phenylpropanoid and flavonoid profiles of 28 plum varieties belonging to P.
      domestica and related species as well as hybrids. A total of 49 phenolic
      compounds extracted from the fruit skin were quantitatively evaluated in an HPLC
      DAD-based metabolomic study. The total phenolic contents of the cultivars varied
      among 0.4-29.9 mg/g fresh weight. The predominant anthocyanins were glycosides of
      cyanidin and peonidin, and rutin was the principal flavonol, whereas
      neochlorogenic acid and n-chlorogenic acid were the main hydroxycinnamic acids.
      Aside from these major phenolic classes, a group of tentatively identified
      flavones and several acylated flavonoids were also found. Principal component
      analysis revealed that anthocyanins and hydroxycinnamic acids contributed most to
      variety separation. The heterogeneity between the different varieties was also
      assessed using hierarchical cluster analysis of sample phenolics profile. A
      simple separation of species could not be found confirming the close relationship
      among them.

PMID- 23140500
TI  - Gaze transfer in remote cooperation: is it always helpful to see what your
      partner is attending to?
AB  - Establishing common ground in remote cooperation is challenging because nonverbal
      means of ambiguity resolution are limited. In such settings, information about a
      partner's gaze can support cooperative performance, but it is not yet clear
      whether and to what extent the abundance of information reflected in gaze comes
      at a cost. Specifically, in tasks that mainly rely on spatial referencing, gaze
      transfer might be distracting and leave the partner uncertain about the meaning
      of the gaze cursor. To examine this question, we let pairs of participants
      perform a joint puzzle task. One partner knew the solution and instructed the
      other partner's actions by (1) gaze, (2) speech, (3) gaze and speech, or (4)
      mouse and speech. Based on these instructions, the acting partner moved the
      pieces under conditions of high or low autonomy. Performance was better when
      using either gaze or mouse transfer compared to speech alone. However, in
      contrast to the mouse, gaze transfer induced uncertainty, evidenced in delayed
      responses to the cursor. Also, participants tried to resolve ambiguities by
      engaging in more verbal effort, formulating more explicit object descriptions and
      fewer deictic references. Thus, gaze transfer seems to increase uncertainty and
      ambiguity, thereby complicating grounding in this spatial referencing task. The
      results highlight the importance of closely examining task characteristics when
      considering gaze transfer as a means of support. 

PMID- 23140501
TI  - Enhanced proliferation and osteogenic differentiation of human umbilical cord
      blood stem cells by L-ascorbic acid, in vitro.
AB  - The multilineage potentiality of cord blood stem cells has been experimentally
      proven in a number of cell based therapies. Umbilical cord blood (UCB) derived
      mesenchymal stem cells (MSCs), on prolonged exposure with Lascorbic acid have
      been successfully differentiated in to osteoblasts (bone forming cells) without
      altering the phenotype of the cells. In this case study, the role of L-ascorbic
      acid on collagen biosynthesis and mineral deposition in MSCs has been assessed,
      which are ultimately matured in to an insoluble extra cellular matrix (ECM),
      giving mechanical strength to the bone cells. Moreover, up to specific
      concentration of L-ascorbic acid (250MUM), proliferation as well as
      differentiation potential of the cells remains unaltered. Further increase in
      concentrations of L-ascorbic acid (500 MUM) reduced the cell proliferation and
      subsequently leads to morphological changes in the cultures. This may be due to
      an immature antioxidant defense system, which can be overcome by treating the
      cell cultures with antioxidants. Our final results conclude that Lascorbic acid
      has positive effect on the ostogenic differentiation of cord blood stem cells,
      and the concentration of ascorbic acid is vital in cell proliferation and
      differentiation.

PMID- 23140502
TI  - Human amniotic fluid stem cells as an attractive tool for clinical applications.
AB  - Recent studies support cell based therapies for several diseases. Human fetal
      stem cells have received much attention for developing new therapeutic
      strategies. Recently, our group and others have successfully isolated and
      expanded karyotypically normal stem cells from an alternative fetal source, the
      human second trimester amniotic fluid (AF) and performed a systematic phenotypic
      and molecular analysis. The main characteristics of amniotic fluid stem cells
      (hAFSCs) are their fetal origin, the high number of isolated cells, their wide
      differentiation properties and their rapid expansion in vitro. These
      characteristics render hAFSCs as a very attractive tool for clinical applications
      based on cell therapy. The use of hAFSC transplantation has been studied in a
      variety of disease animal models related to bone regeneration, myocardial
      infarction, acute kidney injury, acute hepatic failure, skin injury, ischemic
      hind limb or cancer. The major aim of this review is to summarize the advent of
      hAFSCs capabilities into novel therapeutic modalities and discuss their potential
      use in future pre-clinical and clinical studies.

PMID- 23140503
TI  - Functional interaction between charged nanoparticles and cardiac tissue: a new
      paradigm for cardiac arrhythmia?
AB  - AIM: To investigate the effect of surface charge of therapeutic nanoparticles on
      sarcolemmal ionic homeostasis and the initiation of arrhythmias. MATERIALS &
      METHODS: Cultured neonatal rat myocytes were exposed to 50 nm-charged polystyrene
      latex nanoparticles and examined using a combination of hopping probe scanning
      ion conductance microscopy, optical recording of action potential characteristics
      and patch clamp. RESULTS: Positively charged, amine-modified polystyrene latex
      nanoparticles showed cytotoxic effects and induced large-scale damage to
      cardiomyocyte membranes leading to calcium alternans and cell death. By contrast,
      negatively charged, carboxyl-modified polystyrene latex nanoparticles (NegNPs)
      were not overtly cytotoxic but triggered formation of 50-250-nm nanopores in the
      membrane. Cells exposed to NegNPs revealed pro-arrhythmic events, such as delayed
      afterdepolarizations, reduction in conduction velocity and pathological increment
      of action potential duration together with an increase in ionic current
      throughout the membrane, carried by the nanopores. CONCLUSION: The utilization of
      charged nanoparticles is a novel concept for targeting cardiac excitability.
      However, this unique nanoscopic investigation reveals an altered
      electrophysiological substrate, which sensitized the heart cells towards
      arrhythmias.

PMID- 23140505
TI  - Diastereoselective and enantioselective desymmetrization of alpha-substituted
      cyclohexadienones via intramolecular Stetter reaction.
AB  - Highly diastereoselective and enantioselective desymmetrization of alpha
      substituted cyclohexadienones via NHC-catalyzed intramolecular Stetter reaction
      was realized. Amino-indanol derived triazolium salt bearing a C(6)F(5) group was
      found to be the optimal catalyst precursor in the intramolecular Stetter reaction
      furnishing tricyclic products bearing multi-stereocenters in up to 96% yield and
      >99% ee.

PMID- 23140504
TI  - RabGDI controls axonal midline crossing by regulating Robo1 surface expression.
AB  - BACKGROUND: Axons navigate to their future synaptic targets with the help of
      choice points, intermediate targets that express axon guidance cues. Once they
      reach a choice point, axons need to switch their response from attraction to
      repulsion in order to move on with the next stage of their journey. The
      mechanisms underlying the change in axonal responsiveness are poorly understood.
      Commissural axons become sensitive to the repulsive activity of Slits when they
      cross the ventral midline of the CNS. Responsiveness to Slits depends on surface
      expression of Robo receptors. In Drosophila, Commissureless (Comm) plays a
      crucial regulatory role in midline crossing by keeping Robo levels low on
      precommissural axons. Interestingly, to date no vertebrate homolog of comm has
      been identified. Robo3/Rig1 has been shown to control Slit sensitivity before the
      midline, but without affecting Robo1 surface expression. RESULTS: We had
      identified RabGDI, a gene linked to human mental retardation and an essential
      component of the vesicle fusion machinery, in a screen for differentially
      expressed floor-plate genes. Downregulation of RabGDI by in ovo RNAi caused
      commissural axons to stall in the floor plate, phenocopying the effect observed
      after downregulation of Robo1. Conversely, premature expression of RabGDI
      prevented commissural axons from entering the floor plate. Furthermore, RabGDI
      triggered Robo1 surface expression in cultured commissural neurons. Taken
      together, our results identify RabGDI as a component of the switching mechanism
      that is required for commissural axons to change their response from attraction
      to repulsion at the intermediate target. CONCLUSION: RabGDI takes over the
      functional role of fly Comm by regulating the surface expression of Robo1 on
      commissural axons in vertebrates. This in turn allows commissural axons to switch
      from attraction to repulsion at the midline of the spinal cord.

PMID- 23140506
TI  - A mark that is no mark? Queer women and violence in HIV discourse.
AB  - Lesbian, bisexual and queer women are invisible and ignored in HIV discourse, as
      epidemiological classifications result in their institutionalised exclusion from
      risk categories. Simultaneously, these women live with HIV, often in situations
      of societal exclusion and under threat of violence. In this paper, we consider
      the connections between discourse and violence to examine how both are reproduced
      through, applied to and dependent upon people. The ways lesbian, bisexual and
      queer women do (or do not) appear in HIV discourse tells us much about how people
      and categories operate in the global pandemic. The fault-lines of lesbian,
      bisexual and queer women's constrained visibility in HIV discourse can be seen in
      situations where they are exposed to HIV transmission through homophobic sexual
      assault. In dominant HIV discursive practices, such homophobic assault leaves
      Judith Butler's 'mark that is no mark', recording neither its violence nor its
      'non-heterosexuality'. Structural violence theory offers a means to understand
      direct and indirect violence as it pertains to HIV and lesbian, bisexual and
      queer women. We call for forms of modified structural violence theory that better
      attend to the ways in which discourse connects with material realities. Our
      theoretical and epidemiological lens must be broadened to examine how anti
      lesbian, bisexual and queer-women bias affects transnational understandings of
      human worth.

PMID- 23140507
TI  - Dextromethorphan attenuates LPS-induced adhesion molecule expression in human
      endothelial cells.
AB  - OBJECTIVE: This study examines the effect of Dextromethorphan (d-3-methoxy-17
      methylmorphinan; DXM), a commonly used cough-suppressing drug, on the expression
      of VCAM-1 and ICAM-1 in human umbilical vein endothelial cells (HUVECs)
      stimulated with lipopolysaccharide (LPS). METHODS: The effect of DXM on
      expression of cell adhesion molecules induced by LPS was evaluated by monocyte
      bindings in vitro and ex vivo and transmigration assays. The signaling pathways
      involved in the inflammation inhibitory effect of DXM were analyzed by Western
      blot and immunofluorescent stain. RESULTS: Pretreatment of HUVECs with DXM
      inhibited LPS-induced adhesion of THP-1 cells in vitro and ex vivo, and reduced
      transendothelial migration of these cells. Furthermore, treatment of HUVECs with
      DXM can significantly decrease LPS-induced expression of ICAM-1 and VCAM-1. DXM
      abrogated LPS-induced phosphorylation of ERK and Akt. The translocation of early
      growth response gene-1 (Egr-1), a downstream transcription factor involved in the
      mitogen-activated kinase (MEK)-ERK signaling pathway, was suppressed by DXM
      treatment. Furthermore, DXM inhibited LPS-induced IkappaBalpha degradation and
      nuclear translocation of p65. CONCLUSIONS: Dextromethorphan inhibits the adhesive
      capacity of HUVECs by reducing the LPS-induced ICAM-1 and VCAM-1 expression via
      the suppression of the ERK, Akt, and NF-kappaB signaling pathways. Thus, DXM is a
      potential anti-inflammatory therapeutic that may modulate atherogenesis.

PMID- 23140508
TI  - Disrupted adenovirus-based vaccines against small addictive molecules circumvent
      anti-adenovirus immunity.
AB  - Adenovirus (Ad) vaccine vectors have been used for many applications due to the
      capacity of the Ad capsid proteins to evoke potent immune responses, but these
      vectors are often ineffective in the context of pre-existing anti-Ad immunity.
      Leveraging the knowledge that E1(-)E3(-) Ad gene transfer vectors are potent
      immunogens, we have developed a vaccine platform against small molecules by
      covalently coupling analogs of small molecules to the capsid proteins of
      disrupted Ad (dAd5). We hypothesized that the dAd5 platform would maintain
      immunopotency even in the context of anti-Ad neutralizing antibodies. To test
      this hypothesis, we coupled cocaine and nicotine analogs, GNE and AM1, to dAd5
      capsid proteins to generate dAd5GNE and dAd5AM1, respectively. Mice were pre
      immunized with Ad5Null, resulting in high titer anti-Ad5 neutralizing antibodies
      comparable to those observed in the human population. The dAd5GNE and dAd5AM1
      vaccines elicited high anti-cocaine and anti-nicotine antibody titers,
      respectively, in both naive and Ad5-immune mice, and both functioned to prevent
      cocaine or nicotine from reaching the brain of anti-Ad immune mice. Thus,
      disrupted Ad5 evokes potent humoral immunity that is effective in the context of
      pre-existing neutralizing anti-Ad immunity, overcoming a major limitation for
      current Ad-based vaccines.

PMID- 23140510
TI  - Network approaches to drug discovery.
AB  - INTRODUCTION: Advances in genomics technologies are providing a very large amount
      of data on genome-wide gene expression profiles, protein molecules and their
      interactions with other macromolecules and metabolites. Molecular interaction
      networks provide a useful way to capture this complex data and comprehend it.
      Networks are beginning to be used in drug discovery, in many steps of the modern
      discovery pipeline, with large-scale molecular networks being particularly useful
      for the understanding of the molecular basis of the disease. AREAS COVERED: The
      authors discuss network approaches used for drug target discovery and lead
      identification in the drug discovery pipeline. By reconstructing networks of
      targets, drugs and drug candidates as well as gene expression profiles under
      normal and disease conditions, the paper illustrates how it is possible to find
      relationships between different diseases, find biomarkers, explore drug
      repurposing and study emergence of drug resistance. Furthermore, the authors also
      look at networks which address particular important aspects such as off-target
      effects, combination-targets, mechanism of drug action and drug safety. EXPERT
      OPINION: The network approach represents another paradigm shift in drug discovery
      science. A network approach provides a fresh perspective of understanding
      important proteins in the context of their cellular environments, providing a
      rational basis for deriving useful strategies in drug design. Besides drug target
      identification and inferring mechanism of action, networks enable us to address
      new ideas that could prove to be extremely useful for new drug discovery, such as
      drug repositioning, drug synergy, polypharmacology and personalized medicine.

PMID- 23140509
TI  - Intra-genomic GC heterogeneity in sauropsids: evolutionary insights from cDNA
      mapping and GC(3) profiling in snake.
AB  - BACKGROUND: Extant sauropsids (reptiles and birds) are divided into two major
      lineages, the lineage of Testudines (turtles) and Archosauria (crocodilians and
      birds) and the lineage of Lepidosauria (tuatara, lizards, worm lizards and
      snakes). Karyotypes of these sauropsidan groups generally consist of
      macrochromosomes and microchromosomes. In chicken, microchromosomes exhibit a
      higher GC-content than macrochromosomes. To examine the pattern of intra-genomic
      GC heterogeneity in lepidosaurian genomes, we constructed a cytogenetic map of
      the Japanese four-striped rat snake (Elaphe quadrivirgata) with 183 cDNA clones
      by fluorescence in situ hybridization, and examined the correlation between the
      GC-content of exonic third codon positions (GC3) of the genes and the size of
      chromosomes on which the genes were localized. RESULTS: Although GC3 distribution
      of snake genes was relatively homogeneous compared with those of the other
      amniotes, microchromosomal genes showed significantly higher GC3 than
      macrochromosomal genes as in chicken. Our snake cytogenetic map also identified
      several conserved segments between the snake macrochromosomes and the chicken
      microchromosomes. Cross-species comparisons revealed that GC3 of most snake
      orthologs in such macrochromosomal segments were GC-poor (GC3 < 50%) whereas
      those of chicken orthologs in microchromosomes were relatively GC-rich (GC3 >=
      50%). CONCLUSION: Our results suggest that the chromosome size-dependent GC
      heterogeneity had already occurred before the lepidosaur-archosaur split, 275
      million years ago. This character was probably present in the common ancestor of
      lepidosaurs and but lost in the lineage leading to Anolis during the
      diversification of lepidosaurs. We also identified several genes whose GC-content
      might have been influenced by the size of the chromosomes on which they were
      harbored over the course of sauropsid evolution.

PMID- 23140512
TI  - Neuroendocrine carcinoma of the thyroid causing adrenocorticotrophic hormone
      dependent Cushing's syndrome.
AB  - BACKGROUND: Cushing's syndrome (CS) due to ectopic adrenocorticotrophic hormone
      (ACTH) and/or ectopic corticotropic releasing hormone (CRH) secretion accounts
      for <10% of all CS. Neuroendocrine carcinomas rarely cause CS. These carcinomas
      have been found to secrete either ACTH or rarely CRH. Herein we report a case of
      neuroendocrine carcinoma originating from the thyroid as the source of ACTH
      dependent CS. SUMMARY: A 30-year-old woman with features of CS presented with
      severe respiratory distress. Six months before that, she was diagnosed with
      primary hypothyroidism and started on levothyroxine (LT4) therapy. Biochemical
      evaluation was done, and nonsuppressed serum cortisol levels following
      dexamethasone with high ACTH confirmed a diagnosis of ACTH-dependent CS. Magnetic
      resonance imaging of the brain showed a bulky pituitary gland. Adrenal imaging
      showed bilateral adrenal hyperplasia. A computerized tomography scan showed a
      large anterior mediastinal mass arising from the neck and extending behind the
      transverse aortic arch. She underwent emergency thoracotomy due to rapidly
      progressive superior mediastinal syndrome and left vocal cord palsy. At surgery,
      the mass was seen originating from the thyroid and the thymus was compressed
      posteriorly. Near total thyroidectomy and thymectomy with removal of pericardial
      seedlings were done. Histopathology revealed sheets, cords, and nests of round or
      oval tumor cells with hyperchromatic nuclei and scant cytoplasm with local
      invasion and lymphovascular embolization suggestive of a neuroendocrine carcinoma
      arising from thyroid, staining positive for cytokeratin, synaptophysin, and
      chromogranin-A, and negative for calcitonin and carcinoembryonic antigen.
      CONCLUSIONS: Here we report a case of a neuroendocrine tumor of the thyroid
      causing ACTH-dependent CS. The tumor was negative for calcitonin staining,
      indicating that this was not a medullary carcinoma of the thyroid. Neuroendocrine
      carcinomas originating from the thyroid gland are very rare. A thyroid tumor of
      neuroendocrine origin causing ACTH-dependent CS has not been reported previously.

PMID- 23140511
TI  - Malignant mesothelioma of the tunica vaginalis testis: a malignancy associated
      with recurrent epididymitis?
AB  - A 53-year-old Taiwanese male had several episodes of left epididymitis with
      hydrocele refractory to antibiotic treatment. Partial epididymectomy plus
      preventive vasectomy were planned, and, incidentally, an ill-defined nodule was
      found lying on the tunica vaginalis near the epididymal head. The pathological
      diagnosis was malignant mesothelioma of the tunica vaginalis testis. Radical
      orchiectomy with wide excision of the hemi-scrotal wall was performed. So far,
      there is no evidence of recurrence after more than 3 years of follow-up.
      Malignant tumor should be considered in the case of recurrent epididymitis
      refractory to empirically effective antibiotic treatment. Although the nature of
      this tumor is highly fatal, the malignancy can possibly be cured by early and
      aggressive surgical treatment.

PMID- 23140513
TI  - Dynamic modelling of costs and health consequences of school closure during an
      influenza pandemic.
AB  - BACKGROUND: The purpose of this article is to evaluate the cost-effectiveness of
      school closure during a potential influenza pandemic and to examine the trade-off
      between costs and health benefits for school closure involving different target
      groups and different closure durations. METHODS: We developed two models: a
      dynamic disease model capturing the spread of influenza and an economic model
      capturing the costs and benefits of school closure. Decisions were based on
      quality-adjusted life years gained using incremental cost-effectiveness ratios.
      The disease model is an age-structured SEIR compartmental model based on the
      population of Oslo. We studied the costs and benefits of school closure by
      varying the age targets (kindergarten, primary school, secondary school) and
      closure durations (1-10 weeks), given pandemics with basic reproductive number of
      1.5, 2.0 or 2.5. RESULTS: The cost-effectiveness of school closure varies
      depending on the target group, duration and whether indirect costs are
      considered. Using a case fatality rate (CFR) of 0.1-0.2% and with current cost
      effectiveness threshold for Norway, closing secondary school is the only cost
      effective strategy, when indirect costs are included. The most cost-effective
      strategies would be closing secondary schools for 8 weeks if R0=1.5, 6 weeks if
      R0=2.0, and 4 weeks if R0= 2.5. For severe pandemics with case fatality rates of
      1-2%, similar to the Spanish flu, or when indirect costs are disregarded, the
      optimal strategy is closing kindergarten, primary and secondary school for
      extended periods of time. For a pandemic with 2009 H1N1 characteristics (mild
      severity and low transmissibility), closing schools would not be cost-effective,
      regardless of the age target of school children. CONCLUSIONS: School closure has
      moderate impact on the epidemic's scope, but the resulting disruption to society
      imposes a potentially great cost in terms of lost productivity from parents' work
      absenteeism.

PMID- 23140514
TI  - Volatile composition of oyster leaf (Mertensia maritima (L.) Gray).
AB  - Oyster leaf (Mertensia maritima), also called vegetarian oyster, has a surprising
      oyster-like aroma. Its volatile composition was investigated here for the first
      time. In total, 109 compounds were identified by gas chromatography-mass
      spectrometry (GC-MS) and quantified by GC-FID. The use of GC-olfactometry on both
      polar and nonpolar columns allowed the detection of the molecules having an
      oyster-like, marine odor. Four compounds were identified and confirmed by
      synthesis: (Z)-3-nonenal, (Z)-1,5-octadien-3-ol, (Z,Z)-3,6-nonadienal, and (Z)
      1,5-octadien-3-one. After evaluation of freshly prepared reference samples, these
      compounds were confirmed to be reminiscent of the oyster-like marine notes
      perceived in the tasting of cut leaves.

PMID- 23140516
TI  - Sequence diversity of the intergenic spacer region of the rRNA gene of
      Cryptococcus albidus isolated from the skin of patients with atopic dermatitis
      and healthy individuals.
AB  - The yeast species Cryptococcus albidus var. albidus was found to more often
      colonize the skin surface of patients with atopic dermatitis (77.0%, 47/61) than
      that of  healthy subjects (37.5%, 15/40). The intergenic spacer 1 region of the
      rRNA gene of this species consists of four sequence types: I, II, III and IV.
      Types I and II were predominant among healthy subjects and atopic dermatitis
      patients, respectively.

PMID- 23140515
TI  - A droplet-based, optofluidic device for high-throughput, quantitative
      bioanalysis.
AB  - Analysis of chemical or biomolecular contents in a tiny amount of specimen
      presents a significant challenge in many biochemical studies and diagnostic
      applications. In this work, we present a single-layer, optofluidic device for
      real-time, high-throughput, quantitative analysis of droplet contents. Our device
      integrates an optical fiber-based, on-chip detection unit with a droplet-based
      microfluidic unit. It can quantitatively analyze the contents of individual
      droplets in real-time. It also achieves a detection throughput of 2000 droplets
      per second, a detection limit of 20 nM, and an excellent reproducibility in its
      detection results. In a proof-of-concept study, we demonstrate that our device
      can be used to perform detection of DNA and its mutations by monitoring the
      fluorescent signal changes of the target DNA/molecular beacon complex in single
      droplets. Our approach can be immediately extended to a real-time, high
      throughput detection of other biomolecules (such as proteins and viruses) in
      droplets. With its advantages in throughput, functionality, cost, size, and
      reliability, the droplet-based optofluidic device presented here can be a
      valuable tool for many medical diagnostic applications.

PMID- 23140517
TI  - Instant dentin hypersensitivity relief of a single topical application of an in
      office desensitizing paste containing 8% arginine and calcium carbonate: a split
      mouth, randomized-controlled study.
AB  - OBJECTIVE: The aim of this study was to evaluate the clinical efficacy of an in
      office desensitizing paste containing 8% arginine and calcium carbonate relative
      to calcium carbonate alone in the reduction of dentin hypersensitivity in a
      randomized, double-blind, split-mouth clinical trial. MATERIALS AND METHODS:
      Sixty teeth (30 subjects) with an air blast hypersensitivity score of 2 or 3
      (Schiff Cold Air Sensitivity Scale) were randomly assigned to one of two
      treatment groups: (1) test paste containing 8% arginine and calcium carbonate
      (elmex sensitive professional desensitizing paste) and (2) control paste: paris
      white (calcium carbonate). Tactile and air blast dentin hypersensitivity
      examinations were performed at baseline, immediately after paste application and
      4 and 12 weeks later. RESULTS: A statistically significant difference in air
      blast (p = 0.001) and tactile (p = 0.047) hypersensitivity reduction over time
      was observed between the two therapy modes. After 12-weeks, statistically
      significant differences were indicated between the test and control group with
      respect to baseline-adjusted mean tactile (41.94%; p = 0.038) and air blast
      hypersensitivity scores (46.5%; p = 0.017). CONCLUSIONS: The tested in-office
      desensitizing paste containing 8.0% arginine and calcium carbonate provides
      significantly greater hypersensitivity relief compared to calcium carbonate
      alone.

PMID- 23140518
TI  - Chemical debridement of contaminated titanium surfaces: an in vitro study.
AB  - OBJECTIVE: To compare the efficacy of different chemical solutions when used for
      chemical debridement of biofilm contaminated titanium surfaces in an in-vitro
      experimental study. MATERIALS AND METHODS: Commercially pure titanium discs with
      a diameter of 6.2 mm and height of 2 mm, mirror-polished with a measured surface
      amplitude value SA = 0.037 MUm +/- 0.009 were used as test-surfaces. A biofilm
      was simulated with multi-layers of Staphylococcus epidermidis ATCC359844 covering
      the entire titanium surface. The chemical agents tested were: 3% H2O2, 0.2%
      Chlorhexidine, 24% EDTA-gel, 3% H2O2 mixed with 1.6 g/L TiO2 and sterile saline
      solution. The decontamination effect was evaluated by optical density analysis
      using spectrophotometry and with scanning electron microscopy (SEM) images of the
      remaining biofilm. RESULTS: The suspensions of 3% H2O2 and 1.6 g/L TiO2 or 3%
      H2O2 alone were the most effective in removing S. epidermidis biofilms (p <
      0.05), whereas 0.2% chlorhexidine or 24% EDTA gel had no significant effects. SEM
      images of the remaining biofilms supported the quantitative results indicating
      the higher efficacy of 3% H2O2 and 1.6 g/L TiO2 or 3% H2O2 alone. It also
      revealed that EDTA, despite a non-significant effect on reducing the amount of
      established biofilms, was able to alter the biofilm architecture, as demonstrated
      by increased interspaced regions. CONCLUSIONS: In this in vitro study the
      decontamination potential of a suspension of 3% H2O2 and 1.6 g/L TiO2 or 3% H2O2
      alone were encouraging. Whether such procedures would have a similar effect in
      vivo remains to be determined.

PMID- 23140519
TI  - Expectations and satisfaction with care for periodontal specialist patients.
AB  - OBJECTIVE: The aim of this study was to investigate expectations on and
      satisfaction with treatment among patients referred for comprehensive treatment
      to specialist clinics in periodontology and to explore factors associated with
      satisfaction in regression analysis. MATERIALS AND METHODS: Patients referred for
      comprehensive periodontal treatment were sampled for the study. The study was
      based on a questionnaire in a before-and-after design. The first questionnaire
      was sent to the patients before their first appointment at the specialist clinic.
      The second questionnaire was sent after ~ 6 months. Three questions were used to
      measure expectations and four questions to measure satisfaction. The first
      questionnaire was sent to 273 patients with a response rate of 31% and the second
      questionnaire was sent to 85 patients with a response rate of 73%. In non
      response analysis, no difference between respondents and non-respondents were
      detected as to age and gender. RESULTS: Many of the patients viewed it as
      important or very important to have healthy teeth (98%) and improved well-being
      (93%) after periodontal treatment. More than 50% of the patients were satisfied
      with the relation to the caregiver. When measuring the satisfaction in general,
      42% indicated the highest score on the summarized Dental Visit Satisfaction
      Scale. Having confidence (p <= 0.001) and a good relation (p = 0.001) to the
      caregiver indicated higher satisfaction. CONCLUSION: Having a good relation to
      the caregiver and having confidence in the caregiver seems to indicate satisfied
      patients receiving periodontal treatment at periodontal clinics.

PMID- 23140520
TI  - Metabonomic analysis of water extracts from Chinese and American ginsengs by 1H
      nuclear magnetic resonance: identification of chemical profile for quality
      control.
AB  - BACKGROUND: With the gaining popularity of commercially prepared decoctions of
      herbal medicines on the market, an objective and efficient way to reveal the
      authenticity of such products is urgently needed. Previous attempts to use
      chromatographic or spectroscopic methods to identify ginseng samples made use of
      components derived from methanol extracts of the herb. It was not established
      that these herbs can be distinguished solely from consumable components, which
      are responsible for the clinical efficacy of the herb.In this study,
      metabonomics, or metabolic profiling, based on the application of 1H-Nuclear
      Magnetic Resonance (NMR), is applied to distinguish the water extracts of three
      closely related ginseng species: P. ginseng (from two different cultivated
      regions in China), P. notoginseng and P. quinquefolius. METHODS: A water
      extraction protocol that mimics how ginseng decoctions are made for consumption
      was used to prepare triplicate samples from each herb for analysis. High
      resolution 1H NMR spectroscopy was used to acquire metabolic profiles of the four
      ginseng samples. The spectral data were subjected to multivariate and univariate
      analysis to identify metabolites that were able to distinguish different types of
      ginseng. RESULTS: H NMR metabolic profiling was performed to distinguish the
      water extracts of P. ginseng cultivated in Hebei and Jilin of China, both of
      which were distinguished from extracts of P. notoginseng and P. quinquefolius, by
      unsupervised principle component analysis based on the entire 1H NMR spectral
      fingerprint Statistically significant differences were found for several
      discriminating features traced to common metabolites and the ginsenosides Rg1 and
      Rd, in the 1H NMR spectra. CONCLUSION: This study demonstrated that 1H NMR
      metabonomics can simultaneously distinguish different ginseng species and
      multiple samples of the same species that were cultivated in different regions.
      This technique is applicable to the authentication and quality control of ginseng
      products.

PMID- 23140521
TI  - Vascular tone and Ca(2+) signaling in murine cremaster muscle arterioles in vivo.
AB  - OBJECTIVES: We sought to determine some of the molecular requirements for basal
      state "tone" of skeletal muscle arterioles in vivo, and whether asynchronous
      Ca(2+) waves are involved or not. METHODS: Cremaster muscles of anesthetized
      exMLCK and smGCaMP2 biosensor mice were exteriorized, and the fluorescent
      arterioles were visualized with wide-field, confocal or multiphoton microscopy to
      observe Ca(2+) signaling and arteriolar diameter. RESULTS: Basal state tone of
      the arterioles was ~50%. Local block of Ang-II receptors (AT1 ) or alpha1 
      adrenoceptors (alpha1 -AR) had no effect on diameter, nor did complete block of
      sympathetic nerve activity (SNA). Inhibition of phospholipase C caused dilation
      nearly to the Ca(2+) -free (passive) diameter, as did exposure to nifedipine or 2
      APB. Arterioles were also dilated when treated with SKF96365. High-resolution
      imaging of exMLCK fluorescence (ratio) or GCaMP2 fluorescence in smooth muscle
      cells failed to reveal Ca(2+) waves (although Ca(2+) waves/transients were
      readily detected by both biosensors in small arteries, ex vivo). CONCLUSIONS:
      Arterioles of cremaster muscle have vascular tone of ~ 50%, which is not due to
      alpha1 -AR, AT1 R, or SNA. PLC activity, L-type Ca(2+) channels, 2-APB- and
      SKF96365-sensitive channels are required. Propagating Ca(2+) waves are not
      present. A key role for PLC and InsP3 R in vascular tone in vivo, other than
      producing Ca(2+) waves, is suggested.

PMID- 23140522
TI  - Validity of diagnostic pure-tone audiometry without a sound-treated environment
      in older adults.
AB  - OBJECTIVE: To investigate the validity of diagnostic pure-tone audiometry in a
      natural environment using a computer-operated audiometer with insert earphones
      covered by circumaural earcups incorporating real-time monitoring of
      environmental noise. DESIGN: A within-subject repeated measures design was
      employed to compare air (250 to 8000 Hz) and bone (250 to 4000 Hz) conduction
      pure-tone thresholds, measured in retirement facilities, with thresholds measured
      in a sound-treated booth. STUDY SAMPLE: One hundred and forty-seven adults
      (average age 76 +/- 5.7 years) were evaluated. Pure-tone averages were >= 25 dB
      in 59%, mildly (> 40 dB) elevated in 23%, and moderately (> 55 dB) elevated in 6%
      of ears. RESULTS: Air-conduction thresholds (n = 2259) corresponded within 0 to 5
      dB in 95% of all comparisons between the two test environments. Bone-conduction
      thresholds (n = 1669) corresponded within 0 to 5 dB in 86% of comparisons.
      Average threshold differences (- 0.6 to 1.1) and standard deviations (3.3 to 5.9)
      were within typical test-retest reliability limits. Thresholds recorded showed no
      statistically significant differences (paired samples t-test:p > 0.01) except at
      8000 Hz in the left ear. CONCLUSION: Valid diagnostic pure-tone audiometry can be
      performed in a natural environment with recently developed technology, offering
      the possibility of access to diagnostic audiometry in communities where sound
      treated booths are unavailable.

PMID- 23140523
TI  - Rediscovering the core of public health.
AB  - The success of public health has been its ability to understand contemporary
      health problems, to communicate the needs successfully, to identify solutions,
      and to implement them through programs and policies. In the past 50 years, those
      successes can be attributed largely to control of infectious disease, improved
      maternal and child health, delivery of other personal health care services, and
      changes in behaviors, particularly smoking. Yet health is primarily a product of
      our social, cultural, and physical environments. To continue to improve the
      nation's health and reduce disparities, public health needs to return to its
      historical roots and engage with other sectors to create healthier communities.
      To do so requires expanding public health skills in areas such as quantitative
      policy analysis, communication, and community engagement.

PMID- 23140526
TI  - Construction of multisubstituted tetrahydropyrans by a domino oxa-Michael/Tsuji
      Trost reaction.
AB  - Biologically significant tetrahydropyrans (THP) were synthesized by a Tandem oxa
      Michael/Tsuji-Trost reaction. Different Michael acceptors were investigated, and
      optimal results in terms of diastereoselectivities and yields were obtained with
      nitro olefins. The influence of the reaction parameters, substrate patterns, and
      type of metal counterions on the yield and stereochemical outcome of this process
      is discussed, and an explanation for the observed stereoselectivities is
      proposed.

PMID- 23140525
TI  - The unique architecture and function of cellulose-interacting proteins in
      oomycetes revealed by genomic and structural analyses.
AB  - BACKGROUND: Oomycetes are fungal-like microorganisms evolutionary distinct from
      true fungi, belonging to the Stramenopile lineage and comprising major plant
      pathogens. Both oomycetes and fungi express proteins able to interact with
      cellulose, a major component of plant and oomycete cell walls, through the
      presence of carbohydrate-binding module belonging to the family 1 (CBM1). Fungal
      CBM1-containing proteins were implicated in cellulose degradation whereas in
      oomycetes, the Cellulose Binding Elicitor Lectin (CBEL), a well-characterized
      CBM1-protein from Phytophthora parasitica, was implicated in cell wall integrity,
      adhesion to cellulosic substrates and induction of plant immunity. RESULTS: To
      extend our knowledge on CBM1-containing proteins in oomycetes, we have conducted
      a comprehensive analysis on 60 fungi and 7 oomycetes genomes leading to the
      identification of 518 CBM1-containing proteins. In plant-interacting
      microorganisms, the larger number of CBM1-protein coding genes is expressed by
      necrotroph and hemibiotrophic pathogens, whereas a strong reduction of these
      genes is observed in symbionts and biotrophs. In fungi, more than 70% of CBM1
      containing proteins correspond to enzymatic proteins in which CBM1 is associated
      with a catalytic unit involved in cellulose degradation. In oomycetes more than
      90% of proteins are similar to CBEL in which CBM1 is associated with a non
      catalytic PAN/Apple domain, known to interact with specific carbohydrates or
      proteins. Distinct Stramenopile genomes like diatoms and brown algae are devoid
      of CBM1 coding genes. A CBM1-PAN/Apple association 3D structural modeling was
      built allowing the identification of amino acid residues interacting with
      cellulose and suggesting the putative interaction of the PAN/Apple domain with
      another type of glucan. By Surface Plasmon Resonance experiments, we showed that
      CBEL binds to glycoproteins through galactose or N-acetyl-galactosamine motifs.
      CONCLUSIONS: This study provides insight into the evolution and biological roles
      of CBM1-containing proteins from oomycetes. We show that while CBM1s from fungi
      and oomycetes are similar, they team up with different protein domains, either in
      proteins implicated in the degradation of plant cell wall components in the case
      of fungi or in proteins involved in adhesion to polysaccharidic substrates in the
      case of oomycetes. This work highlighted the unique role and evolution of CBM1
      proteins in oomycete among the Stramenopile lineage.

PMID- 23140527
TI  - Use of oral direct factor Xa inhibiting anticoagulants in elective hip and knee
      arthroplasty: a meta-analysis of efficacy and safety profiles compared with those
      of low-molecular-weight heparins.
AB  - Assessing the efficacy and safety profiles of new oral direct Factor Xa (FXa)
      inhibiting anticoagulants compared with low-molecular-weight heparins (LMWHs) in
      elective total hip and knee arthroplasty (THA and TKA). The literature review
      only searched for randomised-controlled trials (RCTs) published before September
      2011. Five eligible THA RCTs with a total of 12,184 patients and 5 eligible TKA
      RCTs with a total of 13,169 patients were identified. Mantel- Haenszel random
      effects model was used to create meta-analyses of pooled data for each surgical
      group. The primary efficacy outcome was the risk of venous thromboembolism (VTE)
      and all-cause mortality, and the primary safety outcome was the risk of major
      bleeding. The THA and TKA primary efficacy outcome meta-analyses calculated
      relative risks (RR) of 0.55 (95% confidence interval 0.32 to 0.94) and 0.68 (95%
      confidence interval 0.53 to 0.87), respectively in favor of the oral direct FXa
      inhibitors. The primary safety outcome meta-analyses for the THA and TKA surgical
      groups revealed an RR of 1.27 (95% confidence interval 0.56 to 2.86) and 0.94
      (95% confidence interval 0.44 to 1.98), which shows no significant difference
      between oral FXa inhibitors and LMWHs. This review demonstrated that oral direct
      FXa inhibitors have a superior efficacy to LMWHs when used as thromboprophylaxis
      in both THA and TKA. The safety profile of these new oral anticoagulants was not
      significantly different to that of LMWHs.

PMID- 23140528
TI  - Robotic thyroidectomy versus endoscopic thyroidectomy: a meta-analysis.
AB  - BACKGROUND: To conduct a meta-analysis to determine the relative merits of
      robotic thyroidectomy (RT) and endoscopic thyroidectomy (ET). METHODS: A
      literature search was performed to identify comparative studies reporting peri
      operative outcomes for RT and ET. Pooled odds ratios (ORs) and weighted mean
      differences (WMDs) with 95% confidence interval (95% CI) were calculated using
      either a fixed-effects or a random-effects model. RESULTS: Six studies matched
      the selection criteria, which reported on 2048 subjects, of whom 978 underwent RT
      and 1070 underwent ET. Comparing the outcomes of RT with ET, this meta-analysis
      indicated that RT was associated with more complications (WMD = 1.51, 95% CI 1.18
      to 1.94) and greater amount of drainage fluid (WMD = 17.10, 95% CI 5.69 to
      28.51). Meanwhile, operating time (WMD = 1.50, 95% CI -39.59 to 42.58),
      conversion (WMD = 0.63, 95% CI 0.07 to 6.17), post-operative hospital stay (WMD =
      -0.05; 95% CI -0.18 to 0.08), and the number of lymph nodes harvested (WMD =
      0.62, 95% CI -0.29 to 1.53) were similar for both procedures. CONCLUSION: The
      results of this meta-analysis indicated that RT is associated with an increased
      risk of complications and a greater amount of drainage fluid. Therefore, RT does
      not appear to have any advantage over ET. Further studies are required to confirm
      these results.

PMID- 23140530
TI  - Fiber-optic chemical sensors and biosensors (2008-2012).

PMID- 23140529
TI  - Starting to smoke: a qualitative study of the experiences of Australian
      indigenous youth.
AB  - BACKGROUND: Adult smoking has its roots in adolescence. If individuals do not
      initiate smoking during this period it is unlikely they ever will. In high income
      countries, smoking rates among Indigenous youth are disproportionately high.
      However, despite a wealth of literature in other populations, there is less
      evidence on the determinants of smoking initiation among Indigenous youth. The
      aim of this study was to explore the determinants of smoking among Australian
      Indigenous young people with a particular emphasis on the social and cultural
      processes that underlie tobacco use patterns among this group. METHODS: This
      project was undertaken in northern Australia. We undertook group interviews with
      65 participants and individual in-depth interviews with 11 youth aged 13-20 years
      led by trained youth 'peer researchers.' We also used visual methods (photo
      elicitation) with individual interviewees to investigate the social context in
      which young people do or do not smoke. Included in the sample were a smaller
      number of non-Indigenous youth to explore any significant differences between
      ethnic groups in determinants of early smoking experiences. The theory of triadic
      influence, an ecological model of health behaviour, was used as an organising
      theory for analysis. RESULTS: Family and peer influences play a central role in
      smoking uptake among Indigenous youth. Social influences to smoke are similar
      between Indigenous and non-Indigenous youth but are more pervasive (especially in
      the family domain) among Indigenous youth. While Indigenous youth report high
      levels of exposure to smoking role models and smoking socialisation practices
      among their family and social networks, this study provides some indication of a
      progressive denormalisation of smoking among some Indigenous youth. CONCLUSIONS:
      Future initiatives aimed at preventing smoking uptake in this population need to
      focus on changing social normative beliefs around smoking, both at a population
      level and within young peoples' immediate social environment. Such interventions
      could be effectively delivered in both the school and family environments.
      Specifically, health practitioners in contact with Indigenous families should be
      promoting smoke free homes and other anti-smoking socialisation behaviours.

PMID- 23140531
TI  - Thermal injury affecting the small bowel without evidence of bladder perforation
      following transurethral resection of bladder tumour.
AB  - Thermal bowel injury following transurethral bladder tumour resection is a rare
      but potentially lethal complication. This article reports a case of isolated
      bowel perforation without concomitant bladder perforation. Although rare,
      clinicians should be aware of this complication, so that the diagnosis can be
      made promptly.

PMID- 23140532
TI  - Floral markers of cornflower (Centaurea cyanus) honey and its peroxide
      antibacterial activity for an alternative treatment of digital dermatitis.
AB  - Cornflower (Centaurea cyanus) honey can be characterized by a greenish yellow
      color and an intense flavor with a bitter aftertaste. Because cornflower honey
      contains only a limited amount of pollen for the verification of its floral
      origin, one objective was the characterization of its polyphenol and
      norisoprenoid contents to assign floral markers. Here, lumichrome (18.8-43.5
      mg/kg), 7-carboxylumichrome, (Z/E)-3-oxo-retro-alpha-ionol, and 3-oxo-alpha-ionol
      appeared to be quite suitable for distinguishing cornflower honey from other
      unifloral honeys. Additionally, due to its comparably high hydrogen peroxide
      content (0.5-0.9 mM/h) and the associated antibacterial activity, cornflower
      honey was used as an alternative treatment of digital dermatitis on an organic
      dairy farm. Cows affected by this hoof disease often show severe lameness and a
      subsequent decline in milk yield and loss of body condition. The cows' hooves
      treated with cornflower honey showed significantly faster healing than the
      control group without any treatment.

PMID- 23140533
TI  - Injectable hydrogel therapies and their delivery strategies for treating
      myocardial infarction.
AB  - INTRODUCTION: Heart failure following myocardial infarction (MI) impacts millions
      of people each year in the US. The field of tissue engineering has developed
      several potential therapies for treating MI including injectable acellular
      hydrogels. These injectable biomaterials can either be synthetic or naturally
      derived, and have the potential to be delivered minimally invasively. AREAS
      COVERED: This review covers the different methods of delivery and presents the
      initial work on the use of injectable biomaterial scaffolds alone to improve
      cardiac function post-MI. Several naturally derived materials including alginate,
      collagen, chitosan, decellularized tissues, fibrin, hyaluronic acid, keratin, and
      Matrigel, as well as a few synthetic materials have shown promise on their own
      without the addition of therapeutics such as cells or growth factors. These
      biomaterials can be potentially delivered via endocardial, epicardial, or
      intracoronary injections and some can even utilize current catheter technology,
      indicating a potential for avoiding invasive surgical procedures. Once injected
      into the wall of the heart, these hydrogels create a scaffold that provides
      biochemical and structural cues, and the ability for cellular infiltration and
      remodeling of the local environment. EXPERT OPINION: Injectable biomaterials have
      several crucial challenges that should be over come to design optimal therapies
      for MI and heart failure, including optimizing material properties, methods of
      injection and understanding the mechanisms of action. But, studies in both small
      and large animals have shown significant improvement in important parameters
      including wall thickness, vascularization of the ischemic region, left
      ventricular volumes, and cardiac function. Thus, the application of injectable
      biomaterials shows promise for developing into new therapies to treat MI,
      potentially improving millions of lives.

PMID- 23140534
TI  - Choline and betaine intake is inversely associated with breast cancer risk: a two
      stage case-control study in China.
AB  - Few epidemiological studies have evaluated the association of choline and betaine
      intake with breast cancer risk and the results remain inconsistent. This study
      aimed to assess the relationship between dietary intake of choline and betaine
      and the risk of breast cancer among Chinese women. A two-stage case-control study
      was conducted, with 807 cases and 807 age- (5-year interval) and residence
      (rural/urban)-matched controls. A validated food frequency questionnaire was used
      to assess dietary intake by face-to-face interview. An unconditional logistic
      regression model was used to calculate multivariate-adjusted odds ratios (OR) and
      95% confidence intervals (CI). A significant inverse association was found
      between dietary choline and betaine consumption and breast cancer risk. The
      adjusted OR for the highest quartile of intake compared with the lowest were 0.40
      (95% CI = 0.28-0.57, P(trend) < 0.001) for total choline intake, 0.58 (95% CI =
      0.42-0.80, P(trend) < 0.001) for betaine intake and 0.38 (0.27-0.53, P(trend) <
      0.001) for choline plus betaine intake, respectively. Intakes of individual
      choline compouds, choline from glycerophosphocholine, phosphocholine,
      phosphatidylcholine, sphingomyelin and free choline were also negatively
      associated with breast cancer risk. The inverse association between choline
      intake and breast cancer risk was primarily confined to participants with low
      folate level (<242 g/day), with an OR (95% CI) of 0.46 (0.23-0.91) comparing the
      fourth quartile with the first quartile of choline intake (P(trend) = 0.005). The
      present study suggests that consumption of choline and betaine is inversely
      associated with the risk of breast cancer. The association of choline intake with
      breast cancer risk is probably modified by folate intake.

PMID- 23140535
TI  - Lethal effects of water quality on threatened California salamanders but not on
      co-occurring hybrid salamanders.
AB  - Biological invasions and habitat alteration are often detrimental to native
      species, but their interactions are difficult to predict. Interbreeding between
      native and introduced species generates novel genotypes and phenotypes, and human
      land use alters habitat structure and chemistry. Both invasions and habitat
      alteration create new biological challenges and opportunities. In the intensively
      farmed Salinas Valley, California (U.S.A.), threatened California tiger
      salamanders (Ambystoma californiense) have been replaced by hybrids between
      California tiger salamander and introduced barred tiger salamanders (Ambystoma
      tigrinum mavortium). We conducted an enclosure experiment to examine the effects
      habitat modification and relative frequency of hybrid and native California tiger
      salamanders have on recruitment of salamanders and their prey, Pacific chorus
      frogs (Pseudacris regilla). We tested whether recruitment differed among genetic
      classes of tiger salamanders (hybrid or native) and pond hydroperiod (seasonal or
      perennial). Roughly 6 weeks into the experiment, 70% (of 378 total) of salamander
      larvae died in 4 out of 6 ponds. Native salamanders survived (n = 12) in these
      ponds only if they had metamorphosed prior to the die-offs. During die-offs, all
      larvae of native salamanders died, whereas 56% of hybrid larvae died. We
      necropsied native and hybrid salamanders, tested water quality, and queried the
      California Department of Pesticide Regulation database to investigate possible
      causes of the die-offs. Salamander die-offs, changes in the abundance of other
      community members (invertebrates, algae, and cyanobacteria), shifts in salamander
      sex ratio, and patterns of pesticide application in adjacent fields suggest that
      pesticide use may have contributed to die-offs. That all survivors were hybrids
      suggests that environmental stress may promote rapid displacement of native
      genotypes.

PMID- 23140536
TI  - Assessing the effectiveness of rapamycin on angiomyolipoma in tuberous sclerosis:
      a two years trial.
AB  - BACKGROUND: Tuberous sclerosis (TS) is a rare autosomal dominant systemic disease
      with an estimated prevalence of 1/6000. Renal angiomyolipoma (AML) is a benign
      tumour with high morbidity frequently present in TS. The aim of the study was to
      test the effect of rapamycin in reducing the volume of AML in TS. METHODS: Twenty
      four-month prospective open-label, single arm, unicentre Phases II andIII study.
      The primary endpoint was to evaluate the effect of treatment on the reduction of
      at least 50% AML volume from baseline at 24 months. The secondary endpoints were:
      average tumour reduction, surgical complications, skin lesions and drug
      safety.The study population comprised 17 patients, aged >10 years who were
      diagnosed with TS and had >=1 renal AML >2 cm of diameter and had a serum
      creatinine < 2mg/dl and urine protein/creatinine ratio < 22.6 mg/mmol. The trial
      was conducted at Fundacio Puigvert. Rapamycin was given to achieve stable plasma
      levels between 4 and 8 ng/ml. AML volume was estimated using orthogonal
      measurements by MRI at baseline, 6, 12 and 24 months. RESULTS: Ten out of 17
      patients were success responders for the main outcome -58.8%, 95%CI: 32.9% to
      81.6%-. After 6 months of therapy, the mean volume decrease was 55.18% (5.01
      standard error (SE); p<0.001) and 66.38% (4.41 SE; p<0.001) at year 1. There was
      no significant decrease between year 1 and 2. According to RECIST criteria, all
      patients achieved a partial response at year 1 and all but two had already
      achieved this partial response after 6 months.The main analysis was performed
      according to the intention-to-treat principle analysis. Tumour volume was
      analyzed over time by means of mixed models for repeated measurement analysis. We
      used the baseline tumour volume as a covariate for the absolute change and
      percentage change from baseline data. The analysis was performed using SAS
      version 9.2 software, and the level of significance was established at 0.05 (two
      sided). CONCLUSIONS: This study show that mTOR inhibitors are a relatively safe,
      efficacious and less aggressive alternative than currently available options in
      the management of AML in TS. TRIAL REGISTRATION: EudraCT number: 2007-005978-30,
      ClinicalTrials.gov number: NCT0121712.

PMID- 23140537
TI  - Factors that influence fatigue status in Canadian university swimmers.
AB  - The overall purpose of this two-part study was to examine factors that influenced
      fatigue status in university level swimmers. Participants were 25 swimmers (14
      male, 11 female) from one university swim team. A mixed methods approach was
      used. Quantitative data were collected using an orthostatic heart rate test and
      self-report questionnaire at multiple time points throughout a competitive
      season. Qualitative data were collected via focus groups conducted at the end of
      the season. Analysis of the quantitative data indicated high levels of
      accumulated physiological and psychological fatigue that improved with increased
      recovery. Specifically, heart rate indices, form, feeling, and energy level
      improved during taper periods and worsened during and immediately after intensive
      training blocks. Analysis of the qualitative data revealed that one factor
      (flexible structure of training programme) had a positive influence on athletes'
      fatigue while two factors (teammate expectations and balancing school, work, and
      sleep) had a negative influence on athletes' fatigue.

PMID- 23140538
TI  - Osteosarcoma of the jaws: a review of literature and a case report on synchronous
      multicentric osteosarcomas.
AB  - BACKGROUND: In the head and neck region, osteosarcoma is the most common primary
      malignant bone tumor, representing 23% of total head and neck malignancies.
      Osteosarcomas of the jaws are nevertheless rare lesions, representing only 2 to
      10% of all osteosarcomas. This report reviews a single-center histopathology
      experience with craniofacial osteosarcomas, and reports the management of
      unusually large synchronous mandibular and maxillary osteosarcomas in a patient.
      PATIENTS AND METHODS: A search of the hospital pathology database for specimens
      with a histological diagnosis of osteosarcomas submitted between July 1992 and
      May 2011 was made. A chart review of a patient with large synchronous maxillary
      and mandibular osteosarcomas was performed, and is reported. CASE PRESENTATION: A
      21-year-old African man with large maxillary and mandibular tumors under
      palliative care presented with increasing difficulties with eating, speech, and
      breathing. Surgical debulking was performed, with histology confirming
      synchronous osteosarcomas of the mandible and maxilla. The patient is well after
      one year, with no evidence of recurrence, having undergone no further treatment.
      CONCLUSION: Osteosarcomas of the jaw remain enigmatic, and a number of
      difficulties related to their diagnosis and treatment are yet to be resolved.
      True synchronous multicentric osteosarcomas of the jaws are extremely rare but,
      like other osteosarcomas of the jaws, have a favorable outcome, and palliative
      resection of such lesions, though challenging, can therefore lead to an
      enormously improved quality of life and self-image, and may even offer the
      opportunity for cure.

PMID- 23140540
TI  - A novel analytical method, Birth Date Selection Mapping, detects response of the
      Angus (Bos taurus) genome to selection on complex traits.
AB  - BACKGROUND: Several methods have recently been developed to identify regions of
      the genome that have been exposed to strong selection. However, recent
      theoretical and empirical work suggests that polygenic models are required to
      identify the genomic regions that are more moderately responding to ongoing
      selection on complex traits. We examine the effects of multi-trait selection on
      the genome of a population of US registered Angus beef cattle born over a 50-year
      period representing approximately 10 generations of selection. We present results
      from the application of a quantitative genetic model, called Birth Date Selection
      Mapping, to identify signatures of recent ongoing selection. RESULTS: We show
      that US Angus cattle have been systematically selected to alter their mean
      additive genetic merit for most of the 16 production traits routinely recorded by
      breeders. Using Birth Date Selection Mapping, we estimate the time-dependency of
      allele frequency for 44,817 SNP loci using genomic best linear unbiased
      prediction, generalized least squares, and BayesCpi analyses. Finally, we
      reconstruct the primary phenotypes that have historically been exposed to
      selection from a genome-wide analysis of the 16 production traits and gene
      ontology enrichment analysis. CONCLUSIONS: We demonstrate that Birth Date
      Selection Mapping utilizing mixed models corrects for time-dependent pedigree
      sampling effects that lead to spurious SNP associations and reveals genomic
      signatures of ongoing selection on complex traits. Because multiple traits have
      historically been selected in concert and most quantitative trait loci have small
      effects, selection has incrementally altered allele frequencies throughout the
      genome. Two quantitative trait loci of large effect were not the most strongly
      selected of the loci due to their antagonistic pleiotropic effects on strongly
      selected phenotypes. Birth Date Selection Mapping may readily be extended to
      temporally-stratified human or model organism populations.

PMID- 23140541
TI  - Motility-based cell sorting by planar cell chromatography.
AB  - We report here a new methodology for sorting mammalian cells based on their
      intrinsic motility on planar substrates, independent of chemoattractants and
      external fields. This biological analogue of thin layer chromatography consists
      of arrays of asymmetric adhesive islands on tissue culture dishes that rectify
      the random movement of cells and direct their migration in a specific direction.
      We demonstrated the use of planar cell chromatography in the separation of
      mixtures of 3T3 fibroblasts that express constitutively active Rac1 or RhoA and
      mixtures of 3T3 fibroblasts and SH-SY5Y neuroblastoma cells.

PMID- 23140542
TI  - Years in Cologne.
AB  - This review describes the building and scientific activity of the Immunology
      Department at the Institute for Genetics in Cologne, cofounded by Max Delbruck in
      post-World War II Germany. The protagonist, a child of Russian emigrants, became
      interested in antibodies as a postdoc at the Pasteur Institute in Paris and a
      proponent of the antigen-bridge model of T-B cell collaboration during his early
      time in Cologne. He was challenged by the gap between cellular immunology and
      molecular genetics and profited from the advances of the latter as well as
      postwar economic growth in Germany. The Immunology Department became a place, and
      little universe in itself, where young scientists from all over the world came
      together to study cellular and molecular mechanisms of antibody formation. This
      included work on normal and malignant B cells in the human, particularly the
      origin of Hodgkin lymphoma, but the main focus was on B cell development and
      homeostasis, the germinal center reaction, and immunological memory, developing
      recombinase-assisted and conditional gene targeting in mice as a main technical
      tool.

PMID- 23140543
TI  - Breastfeeding practices in urban and rural Vietnam.
AB  - BACKGROUND: The aim of this study was to describe and compare breastfeeding
      practices in rural and urban areas of Vietnam and to study associations with
      possibly influencing person and household factors. This type of study has not
      been conducted in Vietnam before. METHODS: Totally 2,690 children, born from 1st
      March 2008 to 30th June 2010 in one rural and one urban Health and Demographic
      Surveillance Site, were followed from birth to the age of 12 months. Information
      about demography, economy and education for persons and households was obtained
      from household surveys. Standard statistical methods including survival and
      regression analyses were used. RESULTS: Initiation of breastfeeding during the
      first hour of life was more frequent in the urban area compared to the rural
      (boys 40% vs. 35%, girls 49% vs. 40%). High birth weight and living in households
      with large number of assets significantly increased the probability for early
      initiation of breastfeeding. Exclusive breastfeeding at three months of age was
      more commonly reported in the rural than in the urban area (boys 58% vs. 46%,
      girls 65% vs. 53%). The duration of exclusive breastfeeding as well as of any
      breastfeeding was longer in the rural area than in the urban area (medians for
      boys 97 days vs. 81 days, for girls 102 days vs. 91 days). The percentages of
      children with exclusive breastfeeding lasting at least 6 months, as recommended
      by WHO, were low in both areas. The duration of exclusive breastfeeding was
      significantly shorter for mothers with three or more antenatal care visits or
      Caesarean section in both areas. High education level of mothers was associated
      with longer duration of exclusive breastfeeding in the rural area. No significant
      associations were found between duration of exclusive breastfeeding and mother's
      age, household economy indicators or household size. CONCLUSION: Intervention
      programs with the aim to promote breastfeeding are needed. Mothers should
      particularly be informed about the importance of starting breastfeeding early and
      to prolong exclusive breastfeeding. In order to reach the WHO recommendation of
      six months exclusive breastfeeding, we propose an extended maternity leave
      legislation to at least six months.

PMID- 23140544
TI  - The clinical effectiveness and cost-effectiveness of primary stroke prevention in
      children with sickle cell disease: a systematic review and economic evaluation.
AB  - BACKGROUND: Sickle cell disease (SCD) is a recessive genetic blood disorder,
      caused by a mutation in the beta-globin gene. For children with SCD, the risk of
      stroke is estimated to be up to 250 times higher than in the general childhood
      population. Transcranial Doppler (TCD) ultrasonography is a non-invasive
      technique which measures local blood velocity in the proximal portions of large
      intracranial arteries. Screening with TCD ultrasonography identifies individuals
      with high cerebral blood velocity; these children are at the highest risk of
      stroke. A number of primary stroke prevention strategies are currently used in
      clinical practice in the UK including blood transfusion, treatment with
      hydroxycarbamide and bone marrow transplantation (BMT). No reviews have yet
      assessed the clinical effectiveness and cost effectiveness of primary stroke
      prevention strategies in children with SCD identified to be at high risk of
      stroke using TCD ultrasonography. OBJECTIVE: To assess the clinical effectiveness
      and cost-effectiveness of primary stroke prevention treatments for children with
      SCD who are identified (using TCD ultrasonography) to be at high risk of stroke.
      DATA SOURCES: Electronic databases were searched from inception up to May 2011,
      including the Cochrane Database of Systematic Reviews (CDSR), the Cochrane
      Central Register of Controlled Trials (CENTRAL), the Database of Abstracts of
      Reviews of Effects (DARE), EMBASE, the Health Technology Assessment (HTA)
      database, ISI Web of Science Proceedings, ISI Web of Science Citation Index, the
      NHS Economic Evaluation Database (NHS EED) and MEDLINE. REVIEW METHODS: The
      assessment was conducted according to accepted procedures for conducting and
      reporting systematic reviews and economic evaluations. A de novo Markov model was
      developed to determine the cost-effectiveness of TCD ultrasonography and blood
      transfusion, where clinically appropriate, in patients with SCD. RESULTS: Two
      randomised controlled trials met the inclusion criteria involving a study
      population of 209 participants. One compared blood transfusion with standard care
      for children who are identified as being at high risk of stroke using TCD
      ultrasonography. In this trial, one patient in the transfusion group had a stroke
      (1/63) compared with 11 children in the standard care group (11/67). The other
      trial assessed the impact of halting chronic transfusion in patients with SCD.
      Sixteen patients in the transfusion-halted group had an event (16/41) (two
      patients experienced stroke and 14 reverted to abnormal TCD velocity); there were
      no events in the continued-transfusion group (0/38). No meta-analyses of these
      trials were undertaken. No relevant economic evaluations were identified for
      inclusion in the review. The de novo modelling suggests that blood transfusions
      plus TCD scans (compared with just TCD scans) for patients with SCD at high risk
      of stroke, aged >= 2 years, may be good value for money. The intervention has an
      incremental cost-effectiveness ratio of L24,075 per quality-adjusted life-year
      gained, and helps avoid 68 strokes over the lifetime of a population of 1000
      patients. The intervention costs an additional L13,751 per patient and generates
      0.6 extra years of life in full health per patient. The data available for the
      economic analysis are limited. Sensitivity analyses and validation against
      existing data and expert opinion provide some reassurance that the conclusion of
      the model is reliable but further research is required to validate these
      findings. LIMITATIONS: The main limitations relate to the availability of
      published clinical data; no completed randomised controlled trials were
      identified which evaluated the efficacy of either BMT or hydroxycarbamide for
      primary stroke prevention. Both the clinical and cost data available for use in
      the economic analysis are limited. Sensitivity analyses and validation against
      existing data and expert opinion provide some reassurance that the conclusions of
      the model are reliable, but further research is required to validate these
      findings. CONCLUSIONS: The use of TCD ultrasonography to identify children at
      high risk of stroke, and treating these children with prophylactic blood
      transfusions, appears to be both clinically effective and cost-effective compared
      with TCD ultrasonography only. However, given the limitations in the data
      available, further research is required to verify this conclusion. Several
      research recommendations can be proposed from this review. Clinically, more
      research is needed to assess the effects and optimal duration of long-term blood
      transfusion and the potential role of hydroxycarbamide in primary stroke
      prevention. From an economics perspective, further research is required to
      generate more robust data on which to base estimates of cost-effectiveness or
      against which model outputs can be calibrated. More data are required to explain
      how utility weights vary with age, transfusions and strokes. Research is also
      needed around the cost of paediatric stroke in the UK. STUDY REGISTRATION:
      PROSPERO CRD42011001496. FUNDING: The National Institute for Health Research
      Health Technology Assessment programme.

PMID- 23140545
TI  - Metal-organic frameworks as potential drug delivery systems.
AB  - INTRODUCTION: Metal-organic frameworks (MOFs) are a unique class of hybrid porous
      solids based on metals and organic linkers. Compared to traditional porous
      materials, they possess predominance of large surface areas, tunable pore size
      and shape, adjustable composition and functionalized pore surface, which enable
      them unique advantages and promises for applications in adsorption and release of
      therapeutic agents. AREAS COVERED: This review addresses MOFs as a new avenue for
      drug delivery and exhibits their ability to efficiently deliver various kinds of
      therapeutic agents. It also details the requirements that MOFs need to satisfy
      for biomedical application, such as toxicological compatibility, stability,
      particle size, and surface modification. In addition, several approaches used to
      enhance encapsulation efficiency are summarized and parameters influencing
      delivery efficiency are also discussed. EXPERT OPINION: Benefiting from the
      unique advantages of MOFs materials, efficient delivery of various kinds of drugs
      has been achieved in some MOF materials. However, it is only the outset of MOFs
      in drug delivery system, and numerous work need to be done before clinical
      applications, for example, studying their in vivo toxicity, exploring degradation
      mechanisms so as to establish real stability of MOFs in body's liquid, providing
      appropriated surface modification avenue for MOFs, and researching in vivo
      efficiency and pharmacokinetics of drug-loaded MOFs.

PMID- 23140547
TI  - Effect of ranolazine in preventing postoperative atrial fibrillation in patients
      undergoing coronary revascularization surgery.
AB  - BACKGROUND/OBJECTIVE: Ranolazine is a new anti-ischemic agent approved for
      chronic angina with additional electrophysiologic properties. The purpose of the
      present trial was to investigate its effect in preventing postoperative atrial
      fibrillation (POAF) after on-pump coronary artery bypass graft (CABG) surgery.
      METHODS: In the current prospective, randomized, (1 active: 2 control), single
      blind (outcome assessors), single-centre clinical trial we recruited consecutive
      eligible patients scheduled for elective on-pump CABG. Participants were assigned
      to receive either oral ranolazine 375 mg twice daily for 3 days prior to surgery
      and until discharge, or to receive usual care. Patients were monitored for the
      development of POAF. RESULTS: We enrolled 102 patients. Significantly lower
      incidence of POAF was noted in the ranolazine group compared with the control
      group (3 out of 34 patients, 8.8%, vs 21 out of 68 patients, 30.8%; p< 0.001).
      Mean values of left atrial diameter and left ventricular ejection fraction
      between the control and the ranolazine group were not significantly different.
      CONCLUSION: Our findings suggest a protective role of oral ranolazine when
      administered in a moderate dose preoperatively in patients undergoing on-pump
      CABG surgery. Future studies based on a wider sample of patients will eventually
      support our conclusions.

PMID- 23140546
TI  - The impact of smoking on cardiovascular outcomes and comorbidities in statin
      treated patients with coronary artery disease: a post hoc analysis of the GREACE
      study.
AB  - BACKGROUND: Smoking adversely affects cardiovascular disease (CVD) morbidity and
      mortality; however the effect of long-term statin treatment in high risk smokers
      is not entirely clear. The primary endpoint of this post hoc analysis of the
      GREek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) study (n=1,600
      patients with established coronary heart disease, mean follow-up 3-years) was the
      incidence of major CVD events, a composite of death, myocardial infarction,
      revascularization, unstable angina, heart failure, and stroke in statin-treated
      patients (n=880) who continued to smoke (n=129) compared with ex-smokers (n=309)
      and never smokers (n=442) as well as on patients not treated with a statin
      (n=720) of all smoking categories. Secondary endpoints were the effect of smoking
      on chronic kidney disease (CKD) and on non-alcoholic fatty liver disease (NAFLD),
      two major and common independent CVD risk factors. RESULTS: Among statin treated
      patients the hazard ratio (HR) for current smokers compared with never smokers
      was 1.86 [95% confidence interval-(CI) 1.19-2.10); similar was the HR for current
      smokers compared with ex-smokers. Absolute (16.3%) and relative (45.6%) CVD risk
      reduction was great in current smokers on statins compared with those not on a
      statin; however they still had the highest absolute CVD event incidence (19.4%).
      Low high density lipoprotein cholesterol and higher triglycerides may account, at
      least in part, for this. The highest risk of CVD events in any of the 6 groups
      was in the smokers not on a statin (35.7%). CKD and NAFLD were not negatively
      affected by smoking and they do not appear to be implicated in the adverse effect
      of smoking on CVD event rate in patients on a statin. CONCLUSIONS: Statins reduce
      CVD morbidity and mortality in current smokers with CVD, but these remain high in
      terms of absolute incidence compared with ex- and never smokers. CKD and NAFLD
      are not affected by smoking and do not seem to contribute to this high CVD event
      incidence. These make smoking cessation imperative in high risk patients even if
      they are on statins.

PMID- 23140548
TI  - Production of natural fragrance aromatic acids by coexpression of trans-anethole
      oxygenase and p-anisaldehyde dehydrogenase genes of Pseudomonas putida JYR-1 in
      Escherichia coli.
AB  - A gene encoding p-anisaldehyde dehydrogenase (PAADH), which catalyzes the
      oxidation of p-anisaldehyde to p-anisic acid, was identified to be clustered with
      the trans-anethole oxygenase (tao) gene in  Pseudomonas putida  JYR-1.
      Heterologously expressed PAADH in  Escherichia coli  catalyzed the oxidation of
      vanillin, veratraldehyde, and piperonal to the corresponding aromatic acids
      vanillic acid, veratric acid, and piperonylic acid, respectively. Coexpression of
      trans-anethole oxygenase (TAO) and PAADH in  E. coli  also resulted in the
      successful transformation of trans-anethole, isoeugenol, O-methyl isoeugenol, and
      isosafrole to p-anisic acid, vanillic acid, veratric acid, and piperonylic acid,
      respectively, which are compounds found in plants as secondary metabolites.
      Because of the relaxed substrate specificity and high transformation rates by
      coexpressed TAO and PAADH in  E. coli , the engineered strain has potential to be
      applied in the fragrance industry.

PMID- 23140550
TI  - The effects of rest intervals on jumping performance: a meta-analysis on post
      activation potentiation studies.
AB  - The purpose of this meta-analytic review was to examine the extent and quality of
      research on the post-activation potentiation acute effect of rest interval
      manipulation on jumping performance. This manuscript adopted the recommendations
      from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      Statement. Criteria eligibility included crossover, randomised, non-randomised
      and counterbalanced studies that observed the voluntary muscle action-induced
      post-activation potentiation on jumping performance. Fourteen studies selected by
      two independent raters were included in the analysis. The rest intervals involved
      ranges including 0-3, 4-7, 8-12 and >=16 min. The results demonstrated medium
      effect sizes for rest intervals 0-3 and 8-12 min (-0.25, confidence interval
      (CI): -0.51 to 0.01 for 0-3 min; 0.24, CI: -0.02 to 0.49 for 8-12 min) and a
      small effect for other ranges (0.15, CI: -0.08 to 0.38 for 4-7 min; 0.07, CI: 
      0.21 to 0.24 for >=16 min). There was no evidence of heterogeneity for sub-groups
      (I2 = 0%; P < 0.001) and no indication of publication bias (Egger's test, P =
      0.179). While a rest interval of 0-3 min induced a detrimental effect on jump
      performance, the range including 8-12 min had a beneficial impact on jump height.
      Findings suggest that the rest interval manipulation seems to affect post
      activation potentiation magnitude and jump height.

PMID- 23140549
TI  - Engineering secondary cell wall deposition in plants.
AB  - Lignocellulosic biomass was used for thousands of years as animal feed and is now
      considered a great sugar source for biofuels production. It is composed mostly of
      secondary cell walls built with polysaccharide polymers that are embedded in
      lignin to reinforce the cell wall structure and maintain its integrity. Lignin is
      the primary material responsible for biomass recalcitrance to enzymatic
      hydrolysis. During plant development, deep reductions of lignin cause growth
      defects and often correlate with the loss of vessel integrity that adversely
      affects water and nutrient transport in plants. The work presented here describes
      a new approach to decrease lignin content while preventing vessel collapse and
      introduces a new strategy to boost transcription factor expression in native
      tissues. We used synthetic biology tools in Arabidopsis to rewire the secondary
      cell network by changing promoter-coding sequence associations. The result was a
      reduction in lignin and an increase in polysaccharide depositions in fibre cells.
      The promoter of a key lignin gene, C4H, was replaced by the vessel-specific
      promoter of transcription factor VND6. This rewired lignin biosynthesis
      specifically for vessel formation while disconnecting C4H expression from the
      fibre regulatory network. Secondly, the promoter of the IRX8 gene, secondary cell
      wall glycosyltransferase, was used to express a new copy of the fibre
      transcription factor NST1, and as the IRX8 promoter is induced by NST1, this also
      created an artificial positive feedback loop (APFL). The combination of
      strategies-lignin rewiring with APFL insertion-enhances polysaccharide deposition
      in stems without over-lignifying them, resulting in higher sugar yields after
      enzymatic hydrolysis.

PMID- 23140551
TI  - Youth's narratives about family members smoking: parenting the parent- it's not
      fair!
AB  - BACKGROUND: Successful cancer prevention policies and programming for youth must
      be based on a solid understanding of youth's conceptualization of cancer and
      cancer prevention. Accordingly, a qualitative study examining youth's
      perspectives of cancer and its prevention was undertaken. Not surprisingly,
      smoking (i.e., tobacco cigarette smoking) was one of the dominant lines of
      discourse in the youth's narratives. This paper reports findings of how youth
      conceptualize smoking with attention to their perspectives on parental and family
      related smoking issues and experiences. METHODS: Seventy-five Canadian youth
      ranging in age from 11-19 years participated in the study. Six of the 75 youth
      had a history of smoking and 29 had parents with a history of smoking. Youth were
      involved in traditional ethnographic methods of interviewing and photovoice. Data
      analysis involved multiple levels of analysis congruent with ethnography.
      RESULTS: Youth's perspectives of parents and other family members' cigarette
      smoking around them was salient as represented by the theme: It's not fair. Youth
      struggled to make sense of why parents would smoke around their children and
      perceived their smoking as an unjust act. The theme was supported by four
      subthemes: 1) parenting the parent about the dangers of smoking; 2) the good/bad
      parent; 3) distancing family relationships; and 4) the prisoner. Instead of being
      talked to about smoking it was more common for youth to share stories of talking
      to their parents about the dangers of smoking. Parents who did not smoke were
      seen by youth as the good parent, as opposed to the bad parent who smoked.
      Smoking was an agent that altered relationships with parents and other family
      members. Youth who lived in homes where they were exposed to cigarette smoke felt
      like a trapped prisoner. CONCLUSIONS: Further research is needed to investigate
      youth's perceptions about parental cigarette smoking as well as possible linkages
      between youth exposed to second hand smoke in their home environment and
      emotional and lifestyle-related health difficulties. Results emphasize the
      relational impact of smoking when developing anti-tobacco and cancer prevention
      campaigns. Recognizing the potential toll that second-hand smoke can have on
      youth's emotional well-being, health care professionals are encouraged to give
      youth positive messages in coping with their parents' smoking behaviour.

PMID- 23140553
TI  - Sexual and dating violence among adolescents and young adults in Chile: a review
      of findings from a survey of university students.
AB  - This paper synthesises and discusses results from the 2005 Survey of Student Well
      Being, a closed-ended questionnaire administered to students attending general
      education courses at a major public university in Santiago (n = 484 women, 466
      men). The survey included questions on sexual violence (SV) and dating violence
      (DV), public health problems that have received little attention in Chile and
      other Latin-American countries. This paper highlights key findings from a series
      of papers based on these data, noting lessons learned in the Chilean context that
      may be useful for other Latin-American countries. Important gaps in the
      international literature on SV and DV are also discussed. A central finding is
      the high prevalence of SV and DV in this sample of university students,
      warranting further public health attention to these problems. Potentially, the
      findings will contribute to changes in awareness, policy and practice along
      similar lines to efforts that transformed the US landscape regarding SV and DV on
      college campuses in the 1980s.

PMID- 23140555
TI  - Graduate student's guide to necessary skills for nonacademic conservation
      careers.
AB  - Graduate education programs in conservation science generally focus on
      disciplinary training and discipline-specific research skills. However,
      nonacademic conservation professionals often require an additional suite of
      skills. This discrepancy between academic training and professional needs can
      make it difficult for graduate students to identify the skills and experiences
      that will best prepare them for the conservation job market. We analyzed job
      advertisements for conservation-science positions and interviewed conservation
      professionals with experience hiring early-career conservation scientists to
      determine what skills employers of conservation professionals seek; whether the
      relative importance of skills varies by job sector (government, nonprofit, and
      private); and how graduate students interested in careers in conservation science
      might signal competency in key skills to potential employers. In job
      advertisements, disciplinary, interpersonal, and project-management skills were
      in the top 5 skills mentioned across all job sectors. Employers' needs for
      additional skills, like program leadership, conflict resolution and negotiation,
      and technical and information technology skills, varied across sectors. Our
      interview results demonstrated that some skills are best signaled to employers
      via experiences obtained outside thesis or dissertation work. Our findings
      suggest that graduate students who wish to be competitive in the conservation job
      market can benefit by gaining skills identified as important to the job sector in
      which they hope to work and should not necessarily expect to be competent in
      these skills simply by completing their chosen degree path.

PMID- 23140556
TI  - Stereospecific synthesis of m-Hydroxymexiletine enantiomers.
AB  - m-Hydroxymexiletine (MHM) is a metabolite of mexiletine, a well known class IB
      anti-arrhythmic drug, which presents almost twice the activity of the parent
      compound on cardiac voltage-gated sodium channels. Given the different activity
      of mexiletine enantiomers on sodium currents (being the R-isomer the eutomer), it
      is conceivable that (R)- and(S)-MHM could differ in pharmacodynamic and
      pharmacokinetic properties, too. Herein we report the efficient synthesis of MHM
      enantiomers that could represent useful tools for further investigations on
      stereospecific requirements of the voltage-gated sodium channel binding site. MHM
      enantiomers and all the homochiral intermediates were fully characterized. The ee
      values for (R)- and (S)-MHM were >99%, as assessed by capillary electrophoresis
      using beta-cyclodextrin sulfated sodium salt as a chiral selector.

PMID- 23140557
TI  - Antiepileptic drugs (AEDs) polypharmacy could lead to buried pharmacokinetic
      interactions due to CYP450.
AB  - CYP450 enzymes are basics for the metabolism of several medications such as
      numerous AEDs. As AEDs polypharmacy could lead to hidden pharmacokinetic
      interactions due to CYP450, there fore, the aim of this study was to determine a
      proper guide line for AEDs prescription in Iranian epileptic population. A cross
      sectional study of fifty-four patients' (n=23 females; n= 31 males with a mean
      age of 27 years) located in the Epilepsy Ward of Kashani Hospital of Isfahan
      University of Medical Sciences was carried out during the year 2011. Variables
      including sex, age, age of seizureonset, type and number of AEDs were recorded in
      d-Base. Results showed that the number of prescriptions based on AEDs
      polypharmacy was 77.8%. The most important drugs in prescriptions were
      carbamazepine (n=41) that is a potent inducer of CYP450 and valproic acid (n=31)
      that is a potent inhibitor of CYP450 simultaneously. Administration of AEDs was
      based on: three (n=17), four (n=7), five (n=4) or six (n=3) AEDs simultaneously.
      To avoid side effects, in prescribing AEDs that act as CYP450 inhibitors or
      inducers concomitantly, their spectrum of interactions should be predicted.

PMID- 23140554
TI  - Micro total analysis systems: fundamental advances and applications in the
      laboratory, clinic, and field.

PMID- 23140558
TI  - Metabolism of nicotine and 4-(methylnitrosamino)-l-(3-pyridyl)-lbutanone (NNK) in
      menthol and non-menthol cigarette smokers.
AB  - PURPOSE: Menthol in cigarettes has been suggested to inhibit metabolism of
      nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). The objective
      of this study was to investigate the glucuronide metabolite ratios (MR) for
      nicotine (NICGLUC/NIC), cotinine (COTGLUC/COT), trans 3'-hydroxy cotinine
      (3OHCOTGLUC/3OHCOT). 4-methylnitrosamino-1-(3-pyridyl)-1-butanol (NNAL -
      NNALGLUC/NNAL); and the ratio of trans 3'-hydroxy cotinine tocotinine
      (3OHCOT/COT) between adult menthol and non-menthol smokers (AS). METHODS: The
      data was collected from the Total Exposure Study (TES), a stratified, multi
      center, cross-sectional study that included 3,585 AS and 1,077 non-smokers. Daily
      urinary excretion of nicotine and five metabolites, NNAL and NNAL glucuronides,
      and serum cotinine were measured in the AS. The analysis included 1044 menthol
      (448 African-Americans, AA) and 2297 non-menthol (161 AA) AS. RESULTS: Smoking
      mentholated cigarettes did not decrease any of the MR. Race was the most
      important significant main effect for all the MRs. AAs exhibited statistically
      significantly lower NICGLUC/NIC, COTGLUC/COT, NNALGLUC/NNAL and 3OHCOT/COT, but
      higher 3OHCOTGLUC/3OHCOT compared to Whites. Age, liver function, alcoholic
      beverages, etc., were some of the other significant effects for some MRs. Menthol
      was not a statistically significant effect,e.g. the adjusted mean NNALGLUC/NNAL
      between menthol and non-menthol AS was 2.93 vs. 2.80 (p>0.05, AA) and3.38 vs.
      3.35 (p>0.05, Whites). The models only explained 2.6-12.6% of the MR variability.
      Number of cigarettes was the most important factor affecting serum cotinine
      levels. CONCLUSIONS: Menthol does not inhibit the metabolism of nicotine or NNK.
      The daily exposure of related constituents is primarily influenced by number of
      cigarettes smoked per day.

PMID- 23140560
TI  - Expression of nuclear and membrane progesterone receptors in the canine oviduct
      during the periovulatory period.
AB  - Important reproductive events take place in the canine oviduct in the presence of
      increasing concentrations of progesterone (P4). To investigate the potential
      effects of P4 on the canine oviduct, the expression of nuclear (PR) and membrane
      (PGRMC1 and 2, mPRalpha, beta and gamma) P4 receptors was studied by quantitative
      RT-PCR and immunohistochemistry. Oviducts were collected from Beagle bitches
      after the onset of pro-oestrus and before the LH peak (Pre-LH), after the LH peak
      and before ovulation (Pre-ov) and on Days 1, 4 and 7 post-ovulation (n=6
      bitches/stage). PR mRNA concentrations decreased from Pre-LH to Day 7 in the
      ampulla and isthmus, whereas both PGRMC1 and 2 mRNA levels increased over the
      same period. The main change in mPR expression was an increase in mPRbeta and
      gamma mRNAs at Day 7 in the isthmus. Furthermore, PR proteins were expressed in
      the nuclei of luminal epithelial, stromal and muscular cells, whereas the
      expression of PGRMCs and mPRs was primarily cytoplasmic and localised in the
      luminal epithelium. The immunostaining for PR decreased at Day 4 in the stroma
      and muscle, whereas it remained strong in the epithelium from Pre-LH to Day 7.
      PGRMC1 staining was strong at Days 4 and 7 whereas PGRMC2 was highly expressed
      from Pre-ov to Day 7. The most intense immunostaining signals for all three mPRs
      were observed at Day 7. Our results strongly support the hypothesis that P4 is an
      important regulator of oviductal functions in the bitch through complementary
      classical and non-classical P4 pathways. 

PMID- 23140559
TI  - Abundance of female-biased and paucity of male-biased somatically expressed genes
      on the mouse X-chromosome.
AB  - BACKGROUND: Empirical evaluations of sexually dimorphic expression of genes on
      the mammalian X-chromosome are needed to understand the evolutionary forces and
      the gene-regulatory mechanisms controlling this chromosome. We performed a large
      scale sex-bias expression analysis of genes on the X-chromosome in six different
      somatic tissues from mouse. RESULTS: Our results show that the mouse X-chromosome
      is enriched with female-biased genes and depleted of male-biased genes. This
      suggests that feminisation as well as de-masculinisation of the X-chromosome has
      occurred in terms of gene expression in non-reproductive tissues. Several
      mechanisms may be responsible for the control of female-biased expression on
      chromosome X, and escape from X-inactivation is a main candidate. We confirmed
      escape in case of Tmem29 using RNA-FISH analysis. In addition, we identified
      novel female-biased non-coding transcripts located in the same female-biased
      cluster as the well-known coding X-inactivation escapee Kdm5c, likely transcribed
      from the transition-region between active and silenced domains. We also found
      that previously known escapees only partially explained the overrepresentation of
      female-biased X-genes, particularly for tissue-specific female-biased genes.
      Therefore, the gene set we have identified contains tissue-specific escapees
      and/or genes controlled by other sexually skewed regulatory mechanisms. Analysis
      of gene age showed that evolutionarily old X-genes (>100 myr, preceding the
      radiation of placental mammals) are more frequently female-biased than younger
      genes. CONCLUSION: Altogether, our results have implications for understanding
      both gene regulation and gene evolution of mammalian X-chromosomes, and suggest
      that the final result in terms of the X-gene composition (masculinisation versus
      feminisation) is a compromise between different evolutionary forces acting on
      reproductive and somatic tissues.

PMID- 23140561
TI  - Designing messages to promote healthy foods.

PMID- 23140562
TI  - Who said it was easy?

PMID- 23140563
TI  - The development and preliminary validation of the behavior, environment, and
      changeability survey (BECS).
AB  - OBJECTIVE: To develop and test the validity of the Behavior, Environment, and
      Changeability Survey (BECS) for identifying the importance and changeability of
      nutrition, exercise, and stress management behavior and related aspects of the
      environment. DESIGN: A cross-sectional, online survey of the BECS and selected
      validated instruments. SETTING: Ten state universities. PARTICIPANTS: A
      convenience sample of college students (n = 1,283), ages 18-24 years. ANALYSIS:
      Principal component analysis was used to confirm a 6-component structure of the
      BECS in 2 independent samples for the purpose of cross-validation. Internal
      consistency was measured and construct and criterion-related analyses were
      conducted to test the reliability and validity of the BECS subscales. RESULTS:
      Six components representing 34 BECS items were revealed from the original 69
      items and explained 64% of the total variance. Six scales were retained, and
      internal consistency of each ranged from alpha = .82 to .93. BECS Nutrition
      Behavior and Nutrition Changeability scale scores were highest for participants
      in action/maintenance Stages of Change for fruit and vegetable intake.
      CONCLUSIONS AND IMPLICATIONS: There is strong support for the use of the BECS
      when planning health programs to gain insight into behavior that young adults are
      willing to improve, specifically related to nutrition, exercise, and sleep.

PMID- 23140564
TI  - Assessing reliability and validity of the GroPromo audit tool for evaluation of
      grocery store marketing and promotional environments.
AB  - OBJECTIVE: To evaluate reliability and validity of a new tool for assessing the
      placement and promotional environment in grocery stores. METHODS: Trained
      observers used the GroPromo instrument in 40 stores to code the placement of 7
      products in 9 locations within a store, along with other promotional
      characteristics. To test construct validity, customers' receipts were coded for
      percentage of food purchases in each of the categories. RESULTS: Of the 22
      categories tested, 21 demonstrated moderate to high interrater reliability
      (intraclass correlation >= 0.61). When more unhealthy items were placed in
      prominent locations, a higher percentage of money was spent on less-healthy
      items, and a lower percentage of food dollars were spent on fruits and
      vegetables. The prominence of locations was more important than the number of
      locations. CONCLUSIONS AND IMPLICATIONS: The GroPromo tool can be used to assess
      promotional practices in stores. Data may help advocates campaign for more
      healthy food items in key promotional locations.

PMID- 23140565
TI  - Undergrad and overweight: an online behavioral weight management program for
      college students.
AB  - OBJECTIVE: Explore the feasibility of an online behavioral weight management
      program for college students. METHODS: The program focused on behavioral
      strategies to modify eating and exercise behaviors of students interested in
      losing weight and/or developing a healthy lifestyle. Specific tools included
      weekly chat meetings with a facilitator, calorie and fat gram recommendations,
      daily food logs, and exercise guidance. RESULTS: Three hundred thirty-six
      students participated from 2 northeastern universities. Overweight/obese students
      wanting to lose weight had a mean body mass index of 30.6 kg/m(2) at baseline and
      lost an average of 5.1 +/- 6.0 lbs. Those of healthy weight wanting to lose
      weight had a mean body mass index of 22.0 kg/m(2) at baseline and lost an average
      of 1.8 +/- 3.2 lbs. Twenty-three percent of students lost > 5% of their baseline
      weight. CONCLUSIONS AND IMPLICATIONS: Use of an online behavioral weight
      management program may be a feasible way to help college students develop healthy
      eating and exercise behaviors.

PMID- 23140566
TI  - Heart disease nutrition education program increases familiarity with heart
      healthy lifestyle recommendations.

PMID- 23140567
TI  - Low-pressure pulsed focused ultrasound with microbubbles promotes an anticancer
      immunological response.
AB  - BACKGROUND: High-intensity focused-ultrasound (HIFU) has been successfully
      employed for thermal ablation of tumors in clinical settings. Continuous- or
      pulsed-mode HIFU may also induce a host antitumor immune response, mainly through
      expansion of antigen-presenting cells in response to increased cellular debris
      and through increased macrophage activation/infiltration. Here we demonstrated
      that another form of focused ultrasound delivery, using low-pressure, pulsed-mode
      exposure in the presence of microbubbles (MBs), may also trigger an antitumor
      immunological response and inhibit tumor growth. METHODS: A total of 280 tumor
      bearing animals were subjected to sonographically-guided FUS. Implanted tumors
      were exposed to low-pressure FUS (0.6 to 1.4 MPa) with MBs to increase the
      permeability of tumor microvasculature. RESULTS: Tumor progression was suppressed
      by both 0.6 and 1.4-MPa MB-enhanced FUS exposures. We observed a transient
      increase in infiltration of non-T regulatory (non-Treg) tumor infiltrating
      lymphocytes (TILs) and continual infiltration of CD8+ cytotoxic T-lymphocytes
      (CTL). The ratio of CD8+/Treg increased significantly and tumor growth was
      inhibited. CONCLUSIONS: Our findings suggest that low-pressure FUS exposure with
      MBs may constitute a useful tool for triggering an anticancer immune response,
      for potential cancer immunotherapy.

PMID- 23140568
TI  - VANTED v2: a framework for systems biology applications.
AB  - BACKGROUND: Experimental datasets are becoming larger and increasingly complex,
      spanning different data domains, thereby expanding the requirements for
      respective tool support for their analysis. Networks provide a basis for the
      integration, analysis and visualization of multi-omics experimental datasets.
      RESULTS: Here we present VANTED (version 2), a framework for systems biology
      applications, which comprises a comprehensive set of seven main tasks. These
      range from network reconstruction, data visualization, integration of various
      data types, network simulation to data exploration combined with a manifold
      support of systems biology standards for visualization and data exchange. The
      offered set of functionalities is instantiated by combining several tasks in
      order to enable users to view and explore a comprehensive dataset from different
      perspectives. We describe the system as well as an exemplary workflow.
      CONCLUSIONS: VANTED is a stand-alone framework which supports scientists during
      the data analysis and interpretation phase. It is available as a Java open source
      tool from http://www.vanted.org.

PMID- 23140569
TI  - Inflammation, allergy and asthma, complex immune origin diseases: mechanisms and
      therapeutic agents.
AB  - Inflammation, allergy and asthma are the manifestation of multitude reactions of
      biological, cellular and immunological events. The various associated biological,
      cellular, and molecular events with inflammation, allergy and asthma participate
      to induce increased vascular permeability, vasodilatation, cellular migration,
      increased mucus secretion, broncho-constriction, structural changes of airway
      architecture, decline in pulmonary functions, release of intracellular mediators,
      increased formation of reactive oxygen species, cartilage degradation and loss of
      function. The participation of variety of effector cells viz. leukocytes,
      neutrophils, eosinophils, basophils, monocytes, macrophages, mast cells,
      dendritic cells, T-cells, B-cells, NK-cells, lead to cascade of events trigger of
      intracellular mediators (cytokines, chemokines etc.) activating diverse
      biological effects and immune responses. Eicosanoids are major precursors in
      cyclooxygenase and lipooxygenase pathways and play an important role in
      inflammation, allergy and asthma. Such biological and cellular events are further
      enhanced by stress related effects. The wide varieties of synthetic and natural
      compounds have been showed to act on different molecular targets (receptor,
      enzymes, mediators, and cells) involved in inflammation, allergy and asthma and
      to alter produce specific/definite therapeutic activity. The present review
      describes pathogenesis and etiological aspects of inflammation, allergy and
      asthma with few relevant patents which would be immensely useful for researchers
      in the field of immunology and molecular pharmacology to explore new
      avenues/strategies for development of new generation of therapeutically active
      agents for treatment of inflammation and allergic disorders.

PMID- 23140570
TI  - Enhanced bioactivity of internally functionalized cationic dendrimers with PEG
      cores.
AB  - Hybrid dendritic-linear block copolymers based on a 4-arm poly(ethylene glycol)
      (PEG) core were synthesized using an accelerated AB2/CD2 dendritic growth
      approach through orthogonal amine/epoxy and thiol-yne chemistries. The biological
      activity of these 4-arm and the corresponding 2-arm hybrid dendrimers revealed an
      enhanced, dendritic effect with an exponential increase in cell internalization
      concomitant with increasing amine end groups and low cytotoxicity. Furthermore,
      the ability of these hybrid dendrimers to induce endosomal escape combined with
      their facile and efficient synthesis makes them attractive platforms for gene
      transfection. The 4-arm-based dendrimer showed significantly improved DNA binding
      and gene transfection capabilities in comparison with the 2-arm derivative. These
      results combined with the MD simulation indicate a significant effect of both the
      topology of the PEG core and the multivalency of these hybrid macromolecules on
      their DNA binding and delivery capablities.

PMID- 23140571
TI  - Diet enriched with korean pine nut oil improves mitochondrial oxidative
      metabolism in skeletal muscle and brown adipose tissue in diet-induced obesity.
AB  - In this study, we investigated effects of pine nut oil (PNO) on high-fat-diet
      (HFD)-induced obesity and metabolic dysfunction in skeletal muscle and brown
      adipose tissue (BAT). Male C57BL/6 mice were fed a HFD with 15% energy from lard
      and 30% energy from either soybean oil (SBO-HFD) or PNO (PNO-HFD) for 12 weeks.
      The PNO-HFD resulted in less weight gain and intramuscular lipid accumulation
      than the SBO-HFD and was accompanied by upregulation of transcripts and proteins
      related to oxidative metabolism and phosphorylation of AMP-activated protein
      kinase (AMPK), as well as molecules selectively expressed in type I and type IIa
      muscle fibers. In addition, uncoupling protein-1 was upregulated in BAT. These
      beneficial metabolic effects were partly associated with the dual ligand activity
      of pinolenic acid, which is abundant in PNO, for peroxisome proliferator
      activated receptors alpha and delta. Our findings suggest that PNO may have
      potential as a dietary supplement for counteracting obesity and metabolic
      dysregulation.

PMID- 23140572
TI  - Aberrant F8 gene intron 1 inversion with concomitant duplication and deletion in
      a severe hemophilia A patient from Southern Italy.

PMID- 23140573
TI  - Treating mental health in remote communities: what do remote health practitioners
      need?

PMID- 23140574
TI  - Comparative mapping in intraspecific populations uncovers a high degree of
      macrosynteny between A- and B-genome diploid species of peanut.
AB  - BACKGROUND: Cultivated peanut or groundnut (Arachis hypogaea L.) is an important
      oilseed crop with an allotetraploid genome (AABB, 2n = 4x = 40). Both the low
      level of genetic variation within the cultivated gene pool and its polyploid
      nature limit the utilization of molecular markers to explore genome structure and
      facilitate genetic improvement. Nevertheless, a wealth of genetic diversity
      exists in diploid Arachis species (2n = 2x = 20), which represent a valuable gene
      pool for cultivated peanut improvement. Interspecific populations have been used
      widely for genetic mapping in diploid species of Arachis. However, an
      intraspecific mapping strategy was essential to detect chromosomal rearrangements
      among species that could be obscured by mapping in interspecific populations. To
      develop intraspecific reference linkage maps and gain insights into karyotypic
      evolution within the genus, we comparatively mapped the A- and B-genome diploid
      species using intraspecific F2 populations. Exploring genome organization among
      diploid peanut species by comparative mapping will enhance our understanding of
      the cultivated tetraploid peanut genome. Moreover, new sources of molecular
      markers that are highly transferable between species and developed from expressed
      genes will be required to construct saturated genetic maps for peanut. RESULTS: A
      total of 2,138 EST-SSR (expressed sequence tag-simple sequence repeat) markers
      were developed by mining a tetraploid peanut EST assembly including 101,132
      unigenes (37,916 contigs and 63,216 singletons) derived from 70,771 long-read
      (Sanger) and 270,957 short-read (454) sequences. A set of 97 SSR markers were
      also developed by mining 9,517 genomic survey sequences of Arachis. An SSR-based
      intraspecific linkage map was constructed using an F2 population derived from a
      cross between K 9484 (PI 298639) and GKBSPSc 30081 (PI 468327) in the B-genome
      species A. batizocoi. A high degree of macrosynteny was observed when comparing
      the homoeologous linkage groups between A (A. duranensis) and B (A. batizocoi)
      genomes. Comparison of the A- and B-genome genetic linkage maps also showed a
      total of five inversions and one major reciprocal translocation between two pairs
      of chromosomes under our current mapping resolution. CONCLUSIONS: Our findings
      will contribute to understanding tetraploid peanut genome origin and evolution
      and eventually promote its genetic improvement. The newly developed EST-SSR
      markers will enrich current molecular marker resources in peanut.

PMID- 23140575
TI  - Attomole sensitivity of staphylococcal enterotoxin B detection using an aptamer
      modified surface-enhanced Raman scattering probe.
AB  - In this report, we present a new homogeneous detection method for staphylococcal
      enterotoxin B (SEB) utilizing core-shell-structured iron-gold magnetic
      nanoparticles and a gold nanorod surface-enhanced Raman scattering (SERS) probe
      in solution. Peptide ligand (aptamer) functionalized magnetic gold nanorod
      particles were used as scavengers for target SEB. After the SEB molecules were
      separated from the matrix, the sandwich assay procedure was tested by gold
      nanorod particles that act as SERS probes. The binding constant between SEB and
      peptide-nanoparticle complex was determined as 8.0 * 10(7) M(-1). The correlation
      between the SEB concentration and SERS signal was found to be linear within the
      range of 2.5 fM to 3.2 nM. The limit of detection for the homogeneous assay was
      determined as 224 aM (ca. 2697 SEB molecules/20 MUL sample volume). Also, gold
      coated surfaces were used as capture substrates and performances of the two
      methods were compared. Furthermore, the developed method was evaluated for
      investigating the SEB specificity on bovine serum albumin (BSA) and avidin and
      detecting SEB in artificially contaminated milk, blood, and urine.

PMID- 23140576
TI  - Early-stage non-small cell lung cancer in elderly patients: should stereotactic
      radiation therapy be the standard of care?

PMID- 23140577
TI  - QSAR and docking studies of HCV NS3 serine protease inhibitors.
AB  - Hepatitis C virus (HCV) is a Hepacivirus that causes chronic liver disease,
      leading to hepatocellular carcinoma, cirrhosis, and chronic hepatitis in about 3%
      of the world population. In this study, novel HCV NS3 serine protease inhibitors
      based on 93 boceprevir analogs were studied by QSAR analyses using thermodynamic,
      structural and topological descriptors, including E-state descriptors. Novel
      compounds were proposed using the QSAR models. Both models were highly
      predictive, with calibration, leave-one-out validation and external validation R2
      of 0.66, 0.65 and 0.52, respectively. The most promising structures were docked
      into the HCV NS3 serine protease active site demonstrating, then, the high
      affinity of some new structures. 

PMID- 23140578
TI  - Antitumor activity of novel benzensulfonamide derivatives in view of their
      physiochemical properties searched by principal component analysis.
AB  - Relationship between activity and structure of the selected 4-chloro-2-mercapto-5
      methylbenzensulfonamide derivatives with their potential anticancer activity was
      studied. Lipophilicity was determined using two distinct chromatographic methods.
      Moreover, geometry of studied compounds was optimized with the help of HyperChem
      software to obtain some molecular descriptors. Reversed-phase and micellar liquid
      chromatography lipophilicity parameters together with theoretically calculated
      parameters were used to study the relationship between structure and activity.
      Principal component analysis performed firstly on activity data and secondly on
      molecular parameters revealed similar results, which allowed us to divide studied
      set of compounds into three distinct clusters differing in both structure and
      activity. Moreover, stepwise regression analysis led to statistically significant
      equation describing potential anticancer activity of studied derivatives based on
      nuclear energy and log P (partition coefficient) of compounds.

PMID- 23140579
TI  - Cinnamic acid derivatives induce cell cycle arrest in carcinoma cell lines.
AB  - Cinnamic acid derivatives can be found in plant material, and they possess a
      remarkable variety of biological effects. In the present study, we have
      investigated the cytotoxic effects of representative cinnamic acid esters and
      amides. The cytotoxicity was determined by MTT test on human cervix
      adenocarcinoma (HeLa), myelogenous leukemia (K562), malignant melanoma (Fem-x),
      and estrogen-receptor-positive breast cancer (MCF-7) cells, versus peripheral
      blood mononuclear cells (PBMCs) without or with the addition of the plant lectin
      phytohemaglutinin (PHA). The compounds tested showed significant cytotoxicity
      (IC50s between 42 and 166 uM) and furthermore selectivity of these cytotoxic
      effects on the malignant cell lines versus the PBMCs was also seen, especially
      when electron-withdrawing groups, such as a cyano group (compound 5), were
      present on the aromatic rings of the alcohol or amine parts of the cinnamic acid
      derivatives. The additional study on cell cycle phase distribution indicated that
      novel cinnamic acid derivatives inhibit cell growth by induction of cell death.
      Thus, cinnamic acids derivatives represent important lead compounds for further
      development of antineoplastic agents.

PMID- 23140580
TI  - Instilling a research culture in an applied clinical setting.
AB  - This article offers a framework and practical advice to nurture development of a
      research culture within a clinical setting. Information is presented on research
      education, infrastructure, and helping clinicians develop a scientific mindset.
      Economical ways to facilitate a scientist-practitioner approach to clinical
      practice are described, as well as metrics to gauge the success of these efforts.

PMID- 23140581
TI  - From recording discrete actions to studying continuous goal-directed behaviours
      in team sports.
AB  - This paper highlights the importance of examining interpersonal interactions in
      performance analysis of team sports, predicated on the relationship between
      perception and action, compared to the traditional cataloguing of actions by
      individual performers. We discuss how ecological dynamics may provide a potential
      unifying theoretical and empirical framework to achieve this re-emphasis in
      research. With reference to data from illustrative studies on performance
      analysis and sport expertise, we critically evaluate some of the main assumptions
      and methodological approaches with regard to understanding how information
      influences action and decision-making during team sports performance. Current
      data demonstrate how the understanding of performance behaviours in team sports
      by sport scientists and practitioners may be enhanced with a re-emphasis in
      research on the dynamics of emergent ongoing interactions. Ecological dynamics
      provides formal and theoretically grounded descriptions of player-environment
      interactions with respect to key performance goals and the unfolding information
      of competitive performance. Developing these formal descriptions and explanations
      of sport performance may provide a significant contribution to the field of
      performance analysis, supporting design and intervention in both research and
      practice.

PMID- 23140582
TI  - Effects of various physical stress factors on mitochondrial function and reactive
      oxygen species in rat spermatozoa.
AB  - The aim of the present study was to evaluate the effects of various physical
      interventions on the function of epididymal rat spermatozoa and determine whether
      there are correlations among these functional parameters. Epididymal rat
      spermatozoa were subjected to various mechanical (pipetting, centrifugation and
      Percoll gradient separation) and anisotonic conditions, and sperm motility,
      plasma membrane integrity (PMI), mitochondrial membrane potential (MMP) and
      intracellular reactive oxygen species (ROS) were evaluated. Repeated pipetting
      caused a loss in motility, PMI and MMP (P<0.05). Minimal centrifugation force
      (200 g) had no effect on motility, PMI and MMP, whereas an increase in the
      centrifugation force to 400 g or 600 g decreased sperm function (P<0.005).
      Percoll gradient separation increased total motility, PMI and MMP (P<0.05).
      However, the spermatozoa that were subjected to mechanical interventions showed
      high susceptibility to a ROS stimulant (P<0.005). Anisotonic conditions decreased
      motility, PMI and MMP, and hypotonic conditions in particular increased basal ROS
      (P<0.05). In correlation tests, there were strong positive correlations among
      total motility, PMI and MMP, whereas ROS showed no or negatively weak
      correlations with the other parameters. In conclusion, the physical interventions
      may act as important variables, affecting functional parameters of epididymal rat
      spermatozoa. Therefore, careful consideration and proper protocols for handling
      of rat spermatozoa and osmotic conditions are required to achieve reliable
      results and minimise damage.

PMID- 23140583
TI  - Regulation of calcium influx and signaling pathway in cancer cells via TRPV6
      Numb1 interaction.
AB  - Ca(2+) is a critical factor in the regulation of signal transduction and Ca(2+)
      homeostasis is altered in different human diseases. The level of Ca(2+) in cells
      is highly regulated through a diverse class of regulators. Among them is the
      transient receptor potential vanilloid 6 (TRPV6), which is a Ca(2+) selective
      channel that absorbs Ca(2+) in the small intestine. TRPV6 is overexpressed in
      some cancers and exhibits oncogenic potential, but its exact mechanism is still
      poorly understood. The Numb protein is a cell fate determinant that functions in
      endocytosis and as a tumor suppressor via the stabilization of p53. Numb protein
      consisted of four isoforms. Here, we showed a novel function of Numb1, which
      negatively regulates TRPV6 activity. The expression of Numb1 decreased cytosolic
      Ca(2+) concentrations in TRPV6-transfected HEK293 cells. When all the isoforms of
      Numb were depleted using siRNA in a TRPV6 stable cell line, the levels of
      cytosolic Ca(2+) increased. We observed an interaction between Numb1 and TRPV6
      using co-immunoprecipitation. We confirmed this interaction using Fluorescence
      Resolution Energy Transfer (FRET). We identified the TRPV6 and Numb1 binding site
      using TRPV6 C-terminal truncation mutants and Numb1 deletion mutants. The binding
      site in TRPV6 was an aspartic acid at amino acid residue 716, and that binding
      site in Numb1 was arginine at amino acid residue 434. A Numb1 mutant, lacking
      TRPV6 binding activity, failed to inhibit TRPV6 activity. Every isoform of Numb
      knockdown, using an siRNA-based approach in MCF-7 breast cancer cells, not only
      showed enhanced TRPV6 expression but also both the cytosolic Ca(2+) concentration
      and cell proliferation were increased. The down-regulated expression of TRPV6
      using siRNA increased Numb protein expression; however, the cytosolic influx of
      Ca(2+) and proliferation of the cell were decreased. To examine downstream
      signaling during Ca(2+) influx, we performed Western blotting analysis on TRPV6
      upregulated cancer cells (MCF-7, PC-3). Taken together, these results
      demonstrated that Numb1 interacts with TRPV6 through charged residues and
      inhibits its activity via the regulation of protein expression. Moreover, we
      provided evidence for a Ca(2+)-regulated cancer cell signaling pathway and that
      the Ca(2+) channel is a target of cancer cells.

PMID- 23140584
TI  - Vitreoretinal surgery for bilateral macular holes after laser-assisted in situ
      keratomileusis for the correction of myopia: a case report.
AB  - INTRODUCTION: Laser-assisted in situ keratomileusis surgery may induce
      postoperative changes in the vitreomacular interface due to the mechanical
      stretch of the vitreous produced by the suction ring and the shock waves
      generated by the excimer laser and, subsequently, may provoke macular hole
      formation. CASE PRESENTATION: A 53-year-old Spanish woman who had undergone a
      laser-assisted in situ keratomileusis for the correction of myopia in her right
      and left eye (10 years ago) was referred to our department with a complaint of
      decreased visual acuity in both eyes. A fundoscopy and optical coherence
      tomography examination revealed a bilateral full-thickness macular hole. A 23
      gauge sutureless pars plana vitrectomy was performed in both eyes, and 1 month
      after surgery her visual acuity improved and the hole closed. CONCLUSION: The
      development of a bilateral full-thickness macular hole after laser-assisted in
      situ keratomileusis has been reported once. This case study enhances our
      understanding of the vitreoretinal pathology induced by laser-assisted in situ
      keratomileusis, showing the importance of a rigorous follow-up, because
      complications may occur even a decade later. In this case study we must also
      consider the contribution of the underlying myopia to the development of the
      bilateral macular holes.

PMID- 23140586
TI  - Potential of primary kidney cells for somatic cell nuclear transfer mediated
      transgenesis in pig.
AB  - BACKGROUND: Somatic cell nuclear transfer (SCNT) is currently the most efficient
      and precise method to generate genetically tailored pig models for biomedical
      research. However, the efficiency of this approach is crucially dependent on the
      source of nuclear donor cells. In this study, we evaluate the potential of
      primary porcine kidney cells (PKCs) as cell source for SCNT, including their
      proliferation capacity, transfection efficiency, and capacity to support full
      term development of SCNT embryos after additive gene transfer or homologous
      recombination. RESULTS: PKCs could be maintained in culture with stable karyotype
      for up to 71 passages, whereas porcine fetal fibroblasts (PFFs) and porcine ear
      fibroblasts (PEFs) could be hardly passaged more than 20 times. Compared with
      PFFs and PEFs, PKCs exhibited a higher proliferation rate and resulted in a 2
      fold higher blastocyst rate after SCNT and in vitro cultivation. Among the four
      transfection methods tested with a GFP expression plasmid, best results were
      obtained with the NucleofectorTM technology, resulting in transfection
      efficiencies of 70% to 89% with high fluorescence intensity, low cytotoxicity,
      good cell proliferation, and almost no morphological signs of cell stress. Usage
      of genetically modified PKCs in SCNT resulted in approximately 150 piglets
      carrying at least one of 18 different transgenes. Several of those pigs
      originated from PKCs that underwent homologous recombination and antibiotic
      selection before SCNT. CONCLUSION: The high proliferation capacity of PKCs
      facilitates the introduction of precise and complex genetic modifications in
      vitro. PKCs are thus a valuable cell source for the generation of porcine
      biomedical models by SCNT.

PMID- 23140587
TI  - Layer-dependent morphologies of silver on n-layer graphene.
AB  - The distributions of sizes of silver nanoparticles that were deposited on
      monolayer, bilayer, and trilayer graphene films were observed. Deposition was
      carried out by thermal evaporation and the graphene films, placed on SiO2/Si
      substrates, were obtained by the mechanical splitting of graphite. Before the
      deposition, optical microscopy and Raman spectroscopy were utilized to identify
      the number of the graphene layers. After the deposition, scanning electron
      microscopy was used to observe the morphologies of the particles. Systematic
      analysis revealed that the average sizes of the nanoparticles increased with the
      number of graphene layers. The density of nanoparticles decreased as the number
      of graphene layers increased, revealing a large variation in the surface
      diffusion strength of nanoparticles on the different substrates. The mechanisms
      of formation of these layer-dependent morphologies of silver on n-layer graphene
      are related to the surface free energy and surface diffusion of the n-layer
      graphene. The effect of the substrate such as SiO2/Si was investigated by
      fabricating suspended graphene, and the size and density were similar to those of
      supported graphene. Based on a comparison of the results, the different
      morphologies of the silver nanoparticles on different graphene layers were
      theorized to be caused only by the variation of the diffusion barriers with the
      number of layers of graphene.

PMID- 23140588
TI  - Baroreflex function is reduced in Alzheimer's disease: a candidate biomarker?
AB  - The baroreflex (BR) reflects autonomic blood pressure control. Alzheimer's
      disease (AD) affects the autonomic system. Detailed properties of BR in AD are
      unknown. We hypothesized that BR is reduced in AD, and is influenced by autonomic
      effects of cholinesterase inhibitors (ChEI). BR was determined in 18 AD patients,
      11 patients with mild cognitive impairment (MCI) and 19 healthy control subjects.
      In AD, BR was measured again after ChEI treatment. Receiver operating
      characteristic analysis was used to define a BR cutoff value, which was then
      tested in an independent validation sample of 16 AD, 18 MCI, and 18 control
      subjects. BR was lower in AD compared with MCI (p < 0.05) and in MCI compared
      with healthy control subjects (p < 0.01). Receiver operating characteristic
      analysis between AD and healthy control subjects yielded a sensitivity of 89% and
      a specificity of 94%. ChEI treatment increased BR with 66% (p < 0.01). BR was
      reduced in AD and increased after treatment with ChEI. BR might be a good
      biomarker to further explore the link between cardiovascular disease and AD.

PMID- 23140589
TI  - Cellular interactions with photo-cross-linked and pH-sensitive polymersomes:
      biocompatibility and uptake studies.
AB  - Polymeric nanoparticles, specifically polymersomes, are at the leading edge of
      the rapidly developing field of nanotechnology. However, their use for biological
      applications is primarily limited by the biocompatibility of the components.
      Hence, optimization of polymersome synthesis protocols should carefully consider
      aspects of cellular toxicity. In this work, we investigate the viability of HDF
      and HeLa cells treated with photo-cross-linked and pH-sensitive polymersomes. We
      demonstrate how aspects of polymersome preparation conditions such as cross
      linking density and UV irradiation time may affect their cytotoxic properties.
      Additionally, we also study the cellular uptake of our polymersomes into the cell
      types mentioned.

PMID- 23140590
TI  - The appropriate allocation of CEUS in the diagnostic algorithm of liver lesions:
      a debated issue.

PMID- 23140591
TI  - Foreword to guidelines and good clinical practice recommendations for Contrast
      Enhanced Ultrasound (CEUS) in the liver - update 2012.

PMID- 23140592
TI  - Noise-based tube current reduction method with iterative reconstruction for
      reduction of radiation exposure in coronary CT angiography.
AB  - PURPOSE: To investigate the potential of noise-based tube current reduction
      method with iterative reconstruction to reduce radiation exposure while achieving
      consistent image quality in coronary CT angiography (CCTA). MATERIALS AND
      METHODS: 294 patients underwent CCTA on a 64-detector row CT equipped with
      iterative reconstruction. 102 patients with fixed tube current were assigned to
      Group 1, which was used to establish noise-based tube current modulation
      formulas, where tube current was modulated by the noise of test bolus image. 192
      patients with noise-based tube current were randomly assigned to Group 2 and
      Group 3. Filtered back projection was applied for Group 2 and iterative
      reconstruction for Group 3. Qualitative image quality was assessed with a 5 point
      score. Image noise, signal intensity, volume CT dose index, and dose-length
      product were measured. RESULTS: The noise-based tube current modulation formulas
      were established through regression analysis using image noise measurements in
      Group 1. Image noise was precisely maintained at the target value of 35.00 HU
      with small interquartile ranges for Group 2 (34.17-35.08 HU) and Group 3 (34.34
      35.03 HU), while it was from 28.41 to 36.49 HU for Group 1. All images in the
      three groups were acceptable for diagnosis. A relative 14% and 41% reduction in
      effective dose for Group 2 and Group 3 were observed compared with Group 1.
      CONCLUSION: Adequate image quality could be maintained at a desired and
      consistent noise level with overall 14% dose reduction using noise-based tube
      current reduction method. The use of iterative reconstruction further achieved
      approximately 40% reduction in effective dose.

PMID- 23140593
TI  - Main challenges facing the pharmaceutical sector in Buchanan County, Virginia: a
      pilot study.
AB  - INTRODUCTION: Little is known about the challenges facing the pharmaceutical
      sector in rural counties in the USA. The aim of this pilot study is to determine
      the main challenges facing the pharmaceutical sector and suggestions for
      improving the sector in Buchanan County, a poor and marginalized county in
      Central Appalachia, Virginia. METHODS: This cross-sectional study used the drop
      by survey based on the first step of the modified Delphi Interview Technique. A
      convenience sample of healthcare professionals in Buchanan County were asked to
      complete a self-administered survey instrument between May and August 2011.
      RESULTS: A total of 16 healthcare professionals including six pharmacists
      completed the survey. The respondents had worked for an average of 13.4 (SD=10.7)
      years in the County (range: 1-33 years). The main challenges facing the
      pharmaceutical sector were drug abuse (n=11), doctor shopping by patients (n=9),
      early refills (n=7) and drug shortage (n=6). Respondents suggested increased
      patient education by pharmacists (n=6) and better coordination and communication
      between pharmacy and doctor (n=6) to improve the pharmaceutical sector in the
      County. CONCLUSIONS: Drug abuse, doctor shopping, early refills and drug shortage
      are the main challenges facing the pharmaceutical sector in Buchanan County.
      Concerted efforts are required to solve these problems. More research is required
      to confirm these findings.

PMID- 23140594
TI  - Human umbilical cord stem cells ameliorate experimental autoimmune
      encephalomyelitis by regulating immunoinflammation and remyelination.
AB  - Multiple sclerosis (MS) is an irreversible and demyelinating disease of the
      central nervous system, in part influenced by chronic inflammation. There is no
      proven effective therapy to stop the pathological progression of MS, although
      suppressing the immune system to control the inflammatory response may improve
      the clinical performance acutely. Here, we found that mesenchymal stem cells from
      human umbilical cord (hUC-MSCs) could restore behavioral functions and attenuate
      the histopathological deficits of experimental autoimmune encephalomyelitis mice
      over the long term (i.e., 50 days) by suppression of perivascular immune cell
      infiltrations and reduction in both demyelination and axonal injury in the spinal
      cord. These findings suggest that transplantation of hUC-MSCs may be a potential
      therapy for MS.

PMID- 23140595
TI  - Fixation of osteoporotic fractures in the upper limb with a locking compression
      plate.
AB  - Locking Compression Plate (LCP) has the advantageous feature that screws can be
      locked in the plate leaving an angular stable construct. There is no need to have
      contact between the plate and the bone to achieve stability resulting from
      friction of the plate-bone-construct. Therefore the plate does not need to be
      contoured exactly to the bone and the healing bone's periosteal blood supply is
      not affected. The LCP is used as a bridging plate to gain relative stability in
      multi-fragmentary, diaphyseal or metaphyseal fractures. Depending on the
      fracture, the combination hole can also allow the LCP to achieve absolute
      stability similar to conventional fixation techniques. Osteoporotic fractures
      have significant impact on morbidity and mortality. Proximal humeral and distal
      radius fractures are typical examples. These osteoporotic and often comminuted
      fractures are ideal settings/indications for LCP utilization in the upper
      extremity. However, the data quality is due to mostly small study populations not
      so powerful. Unquestionably there has been a clear and fashionable trend to
      choose operative treatment for these fractures, because the angular stability
      allows stable fixation and early functional mobilization.

PMID- 23140596
TI  - Conservative treatment of acetabular both column fractures: does the concept of
      secondary congruence work?
AB  - Complete separation of all bony fragments around the acetabulum in both column
      fractures can lead to extra-anatomical orientation of these fragments around the
      femoral head with the potential of a "secondary congruence". No long-term data
      are known in the literature. We could follow 35 patients were a both column
      fracture was treated non-operatively due to different reasons. Demographics,
      fracture type, additional fracture lesions (comminution, marginal impaction), the
      clinical and radiological result and joint failure (severe arthrosis, FHN, esc.
      THR) were analyzed. The mean age was 38 years, 27 patients were male, eight
      female. All but four were multiply injured with a mean ISS of 22 points. 16
      patients had additional pelvic ring injuries The majority of patients showed a C1
      fracture of the acetabulum (anterior column multifragmentary, posterior column
      simple). 31 patients healed in secondary congruence (88%). Primary displacement
      was half (11,4 mm, 3-27 mm) compared to patients without secondary congruence (20
      mm, 17-22 mm). 80% of the patients had none or only slight pain and 77% had an
      excellent or good functional result (Merle d'Aubigne Score). The rate of joint
      failure due to non-union, femoral head necrosis, posttraumatic degenerative
      changes or pain was relatively low with 17% after a mean of 5 years following
      trauma. In selected patients, conservative treatment of both column fractures can
      lead to acceptable long-term results with a high rate of secondary congruence.

PMID- 23140597
TI  - [Comparison of patellar pain after total knee arthroplasty with conventional
      versus individual femoral rotational alignment].
AB  - PURPOSE OF THE STUDY: The aim of the study was to find out whether the frequency
      and intensity of patellar pain can be affected by individual rotational alignment
      of the femoral component in total knee arthroplasty, as compared with the
      standard 3 degrees of external femoral rotation in conventional procedures.
      MATERIAL AND METHODS: In randomly selected patients treated for knee
      osteoarthritis by total joint replacement between January 2007 and January 2011,
      the occurrence of patellar pain was assessed. The evaluated knees were allocated
      to two groups. Group 1 included 350 knee joints with conventional femoral
      rotational alignment, i.e., 3 degrees of external rotation. Group 2 comprised 380
      knee joints with an individual rotational alignment of the femoral component
      based on the condylar twist angle. Post-operative anterior knee pain was assessed
      on the following scale: 1, no pain; 2, occasional mild pain; 3, moderate pain; 4,
      severe pain. RESULTS: In group 1, 312 knee joints were free from pain, 15
      occasionally experienced mild pain, 15 had moderate and eight had severe pain. A
      total of 23 revision operations were performed for patellar pain at the anterior
      knee and pain around the patella refractory to non-steroidal anti-rheumatic and
      rehabilitation therapy. In group 2, there were 331 pain-free knees, 48 with
      occasional mild pain, one with moderate pain and no knee with severe pain. No
      revision surgery was required. One patient with moderate patellar pain underwent
      surgery for spinal canal stenosis; after that knee pain was only mild. The groups
      were compared, as to pain assessment results, using the test of equality of
      relative frequencies, i.e., score categories 1+2 versus 3+4 of 350 (group 1)
      equalled 23 (6.57%) were compared with 1 (0.26%) of 380 (group 2); the difference
      was significant (p < 0.001). Using the same test for comparison of the frequency
      of repeat operations, i.e., 23 (0.57%) of 350 (group 1) versus 0 (0%) of 380
      (group 2), also gave a significant result (p = 0.001). DISCUSSION: Mild and
      occasional pain was recorded in both groups, suggesting that femoral component
      malrotation is not the only cause of patellar pain following total knee
      arthroplasty. A markedly lower incidence of moderate and severe pain and no need
      for revision surgery found in group 2 provides evidence that the use of
      individual rotational alignment of the femoral component is fully justified.
      CONCLUSIONS: An individual rotational alignment of the femoral component can
      significantly reduce the incidence of moderate to severe patellar pain or even
      need for revision surgery.

PMID- 23140598
TI  - [Comparison of two surgical methods for treatment of idiopathic thoracic
      scoliosis - anterior versus posterior approaches].
AB  - PURPOSE OF THE STUDY: The aim of this retrospective randomised study is a
      comparison of two surgical approaches (anterior versus posterior) for the
      treatment of idiopathic thoracic scoliosis by corrective spondylodesis with
      segmental instrumentation in adolescents aged 13 to 20 years. MATERIAL AND
      METHODS: The study included patients with right-sided idiopathic thoracic
      scoliosis (Cobb's angle, 40 degrees -70 degrees ; Lenke type I). The group of
      patients treated from the posterior approach by fusion and segmental
      instrumentation, involving the use of a hybrid, tworod system or screws only,
      comprised 31 girls with an average age of 14.5 years (group 1). In this group
      three instrumentation systems were used. The patients treated from the anterior
      approach, which included thoracotomy for disc excision, fusion and segmental
      instrumentation with a one- or two-rod system, consisted of 25 girls and six boys
      with an average age of 15.3 years (group 2). In this group four instrumentation
      systems were employed. In all patients radiographs were evaluated before surgery,
      immediately after the procedure and then every 12 months. The evaluation also
      included the operative time, blood loss, length of hospital stay, hospital costs
      and complications. The random selection was based on casting lots. Some patients
      indicated for the anterior approach withdrew after receiving detailed information
      on this procedure and therefore patients operated on from the anterior approach
      before the study had begun were enrolled. The statistical comparison of the
      results of anterior and posterior procedures was made using the two-sample t-test
      or Wilcoxon's test. The Shapiro-Wilk test was used for normality testing and
      Fisher's F-test for the equality of variances. The paired t-test or non
      parametric paired Wilcoxon's test was employed for testing two variables within
      each group. The level of significance was set at 0.05. RESULTS In group 1,
      anteroposterior radiographs showed, on the average, 54.3 degrees  before surgery,
      18.7 degrees  immediately after it and 19.1 degrees  at one year after surgery.
      The sagittal profile before surgery was T5 +30.0 degrees  T12 -57.7 degrees  S1;
      the surgery resulted in reducing thoracic kyphosis by 9.5 degrees  and lumbar
      lordosis by 14.2 degrees . The average operative time was 245.8 min, intra
      operative blood loss was 1095.2 ml and drained blood loss was 636.9 ml. The
      average hospital stay lasted 10.2 days. In group 2, anteroposterior radiographs
      had the average values of 53.7 degrees  pre-operatively, 23.6 degrees  post
      operatively and 25.9 degrees  at one year after surgery. The pre-operative
      sagittal profile was T5 +21.5 degrees  T12 -54.2 degrees  S1 and, post
      operatively, thoracic kyphosis increased by 7.0 degrees  and lumbar lordosis
      decreased by 2.2 degrees . The average operative time was 226.8 min, intra
      operative and drained blood losses were 1095.2 ml and 636.9 ml, respectively, and
      length of hospital stay was 15.5 days.. In group 2, the operative time and intra
      operative blood loss were lower and post-operative drained blood loss (due to
      longer duration of chest drainage) was higher than in group 1. All findings were
      statistically significant. Significant differences between the groups were also
      found in the costs of implants and hospital stay because, for the posterior
      approach, they were higher by a total of 68 466 CZK and 52 250 CZK, respectively.
      DISCUSSION: In the frontal plane, thoracic kyphosis corrections through either
      surgical approach are comparable; in the sagittal plane, surgery from the
      posterior approach results in reducing thoracic kyphosis and that from the
      anterior approach produces a mild increase in it. CONCLUSIONS: In terms of
      surgical treatment selection, the anterior approach is more economical and
      requires spinal fixation and instrumentation to a lesser extent. However,
      prolonged chest wound drainage results in a longer hospital stay. The majority of
      idiopathic scoliosis cases are indicated for a posterior approach. In scoliosis
      with marked hypo-kyphosis or lordosis, an anterior approach can be considered
      because it produces an increase in thoracic kyphosis.

PMID- 23140599
TI  - [Evolution of the technique of arthroscopic reinsertion of the rotator cuff. Our
      experience from the years 1998 to 2008].
AB  - PURPOSE OF THE STUDY: A rotator cuff tear is a relatively frequent cause of pain
      and restricted motion of the shoulder. Some orthopaedists believe that any
      attempt at rotator cuff reconstruction will fail. The aim of this paper is to
      present our experience with arthroscopic reconstruction of rotator cuff tears.
      MATERIAL AND METHODS: Between January 1998 and December 2008, 319 patients with
      an early diagnosis of rotator cuff rupture were treated. The group included 67
      women and 252 men, with an average age of 37 years (range, 24 to 71 years) at the
      time of surgery. The patients indicated for arthroscopic reconstruction had to
      show free motion of the shoulder, had a full thickness tear up to 3 cm in size in
      the sagittal plane and a Patte stage 2 tear in the frontal plane at the maximum.
      The outcome of surgery was evaluated at one year of follow-up and included the
      patient's self-assessment, modified UCLA score and incidence of complications.
      The probability of failure was calculated as an odds ratio of an implant failure
      to failure of the other implants and the probability of repeat surgery in a given
      implant was calculated as a relative risk in relation to the other implants.
      RESULTS: The average operative time was 52 minutes (range, 25 to 85); the average
      UCLA score increased from 10 to 31 points (p<0.00001). An excellent or a good
      result was achieved in 80% of the patients. Rotator cuff reconstruction failed in
      32 patients (11%), of whom 22 (7.6%) underwent revision surgery. The failure was
      due to migration of rotator cuff anchors or thread failure in 14 patients (14/32;
      44%). The GII anchors showed the highest risk of failure, with the odds ratio of
      5.55 (95 % CI, 2.22 to 13.84) for mechanical failure of the method and a relative
      risk of revision surgery of 7.62 (95% CI, 2.86 to 20.27). For comparison, the RC
      anchors had the odds ratio for mechanical failure equal to 0.55 (95 % CI, 0.25 to
      1.24) and the relative risk of repeat surgery equal to 0.41 (95% CI, 0.12 to
      1.43). In addition, 18 complications were recorded. The frequency of deep wound
      infection was 0.7% (2/319). Six patients (2.1%) required repeat surgery for
      symptomatic bursitis and adhesive capsulitis. DISCUSSION: A recent meta-analysis
      has found no significant difference between the results of surgical rotator cuff
      reconstruction and its conservative treatment. We do not support this view but
      present here evidence that, when certain conditions are fulfilled, arthroscopic
      reconstruction can produce a very good clinical outcome. CONCLUSIONS: The
      arthroscopic reconstruction of a rotator cuff tears results in a marked relief of
      pain and improved joint function. An ideal candidate for this treatment should
      show passive free motion at the shoulder joint, no clinical signs of bursitis,
      and mobilisable tendon stumps of the torn rotator cuff. In addition, these
      patients should be highly motivated for post-operative rehabilitation. A suture
      device was most effective in rotator cuff repair. For good fixation into the bone
      it is recommended to use special implants that have a minimal risk of
      dislodgement or anchor thread failure.

PMID- 23140600
TI  - [Surgery for sciatic nerve injuries].
AB  - PURPOSE OF THE STUDY: Injury to the sciatic nerve is a rare event. Apart from war
      time surgery, it usually presents as a closed lesion caused by traction. The aim
      of the study was to evaluate a group of patients treated for sciatic nerve
      injury, with an analysis of the cause for and the outcome of surgery. MATERIAL
      AND METHODS: In this prospective study, the results in ten patients treated
      surgically were evaluated. Five patients underwent exoneurolysis, two were
      treated by end-to-end suture of the nerve and three by suture and sural nerve
      grafting. One patient was lost to follow-up and nine were followed up for
      minimally 24 months after surgery. RESULTS: In the patients treated by
      exoneurolysis, sciatic nerve function recovered in the peroneal division in 60%,
      and in the tibial portion in 100% of them. The result depended mainly on the
      inter val between injury and surgery. Of four patients with direct suture of the
      nerve or with sural nerve grafting, function of the tibial portion recovered in
      three (75%) and that of the peroneal portion in one (25%). CONCLUSIONS: Although
      the course of the sciatic ner ve is ver y long, its surgical treatment is fully
      justified because it shows good results even in buttock-level and thigh-level
      nerve injuries.

PMID- 23140601
TI  - [Intercondylar eminence fracture in children. Results of long-term follow-up].
AB  - PURPOSE OF THE STUDY: An intercondylar eminence fracture is injury more common in
      children and adolescents than in adults. Also if it is considered a benign
      lesion, a displaced medial spine fracture can result in cruciate ligament laxity.
      We report the evaluation of long-term results of conservative and arthroscopic
      stabilisation in children and adolescents with different types of intercondylar
      eminence fracture. MATERIAL AND METHODS: Flirty-eight patients with intercondylar
      eminence fractures, 31 boys and 17 girls, were included in our retrospective
      study. Of them, 33 were at the end of skeletal growth. According to the Meyers
      and McKeever classification, 11 fractures were type I, 20 were type II and 17
      were type III. The first step in the treatment was an attempt at conservative
      reduction. If it failed, arthroscopic reduction with crossed K-wire fixation was
      used. At clinical follow-up, the patients were examined for pain, range of
      motion, level of activity, and the laxity tests were done. RESULTS: Conservative
      treatment was used in all type I cases (100 %), in eight type II cases (40%) and
      three type III cases (18%). The remaining patients were treated by arthroscopic
      reduction with crossed K- wires (type I, 0%; type II, 60%; type III, 82%). Six
      patients (12.5%) had symptoms of persistent anterior instability and five of them
      (10.4%) were indicated for anterior ligament reconstruction at the end of
      skeletal growth. We did not see serious complications. DISCUSSION: Most of the
      authors recommend that type I and type II fractures should be treated
      conservatively; type III is better treated by arthroscopic reduction. Some of
      type II and type III fractures are indicated for minimally invasive surgical
      treatment at once. At the present time at our department, type II and some type
      III fractures are indicated first for conservative reduction and, when this
      fails, arthroscopic reduction with K-wire fixation is used. CONCLUSIONS: The aim
      of our report was to report the results of our study and present our relatively
      conservative way of treatment as the method of choice for treating intercondylar
      eminence fractures in children and adolescents.

PMID- 23140602
TI  - [Subtalar dislocation of the foot].
AB  - PURPOSE OF THE STUDY: Based on a retrospective analysis, the authors present
      their experience with treatment of subtalar dislocation of the foot. MATERIAL AND
      METHODS: Between 1999 and 2011 six patients, all of them men, with the average
      age of 31 years were treated for subtalar fractures. Five patients were diagnosed
      with medial dislocation and one with lateral dislocation. In one patient with
      medial subtalar dislocation it was an open injury. The clinical and radiographic
      results of the patients followed up for 1 to 12 years (average, 7.8 years) were
      retrospectively evaluated. RESULTS: The achieved average score, based on the
      AOFAS ankle and hindfoot scale, was 91.3 points (+/- 9.77; minimum, 73; maximum,
      100). Excellent results were recorded in four patients, good in one and
      satisfactory in the patient with lateral dislocation. Radiographic signs of
      subtalar joint osteoarthritis were found in one patient. No neurological or
      circulation dis - orders, skin necrosis, signs of reflex sympathetic dystrophy,
      aseptic bone necrosis of the talus, infection or joint instability were recorded.
      DISCUSSION: A subtalar dislocation of the foot involves simultaneous dislocation
      of the talocalcaneal and talonavicular joints. It is a rare injury accounting for
      about 1 to 2% of all traumatic dislocations. It may occur as medial, lateral,
      anterior or posterior subtalar dislocation. The results of treatment depend on
      several factors, such as the type of dislocation (medial and open dislocations
      are at higher risk), associated injuries, or damage to deep skin layers, and also
      on an exact diagnosis, early and accurate reduction and sufficiently long foot
      immobilisation.

PMID- 23140604
TI  - [Gun-shot injuries to the abdomen involving the pancreas].
AB  - PURPOSE OF THE STUDY: The aim of the study is to present our experience with the
      diagnosis and therapy of penetrating abdominal injury involving the pancreas
      caused by a gun shot. MATERIAL AND METHODS: The group included patients with gun
      shot abdominal injuries involving the pancreas who were treated at the Department
      of Surgery and the Department of Emergency Medicine at the University Hospital
      Hradec Kralove. The extent of pancreatic injury was assessed using the American
      Association for the Surgery of Trauma (AAST) classification. The factors
      evaluated included the timing of surgery, operative strategy, operative time,
      blood loss, post-operative complications with pancreatic fistulas in particular,
      and the length of hospital stay. Pancreatic fistula was assessed according to the
      ISGPF (International Study Group for Pancreatic Fistula). RESULTS During the
      period of study lasting 10 years, three patients with gun-shot abdominal injuries
      involving the pancreas were treated. DISCUSSION: Pancreatic trauma due to a gun
      shot is a rare injury, but has also been reported in the Czech Republic. In any
      penetrating injury to the abdomen due to a gun shot, surgical exploration is
      always indicated and pancreatic trauma is usually found during the surgery. The
      first step in the procedure is to check all potential sources of bleeding because
      uncontrolled bleeding is the most frequent cause of intra-operative death. In a
      seriously injured patient, the technique of damage control surgery must be
      employed. After the major sources of bleeding have been checked, a thorough
      exploration of all abdominal organs should be performed to ascertain whether the
      main pancreatic duct has not been injured and, if so, in which part of the
      pancreas and to what extent. The correct classification of pancreatic injury
      according to the AAST is necessary to indicate appropriate therapy. Exploration
      for injury to other organs that often accompanies pancreatic trauma is a
      necessity. CONCLUSIONS: Penetrating pancreatic trauma is almost always associated
      with injury to the adjacent organs. All patients with gun-shot injuries to the
      abdomen are indicated for surgical exploration, thus the pancreatic injury is
      often found at the surgical exploration. After bleeding has been controlled, for
      treatment of the injured pancreas, simple drainage, or suture of the pancreatic
      capsule, or pancreatic resection or a patch with an excluded jejunal loop can be
      used. Partial duodenopancreatectomy is the last option because this procedure is
      associated with high morbidity and mortality.

PMID- 23140603
TI  - [Vascular system injuries].
AB  - PURPOSE OF THE STUDY: The aim of this retrospective study is to present our
      experience with the management of injuries to the vascular system at the Trauma
      Centre, University Hospital in Plzen. We show the most frequent mechanisms of
      injury, diagnostic pitfalls, therapeutic options and evaluate both the short-term
      and long-term results of surgical treatment and interventional radiology
      procedures. MATERIAL AND METHODS: We evaluated a group of patients with a serious
      vascular injury who were treated at the Traima Centre during the five-year period
      from January 2006 to December 2010. The group included 82 patients, 59 men and 23
      women, with the average age of 34.5 years. We assessed the success rate of
      vascular reconstruction, primary and secondary graft patency and mortality and
      morbidity rates. Recovery of function in the injured extremities and return of
      the patient to normal daily activities were considered the most important
      parameters. In 28 patients (34%) vascular injury was due to polytrauma, in nine
      (11%) it was part of a combined injury, and 45 patients (55 %) sustained
      monotrauma. Most of the patients (68; 83%) were managed surgically. The most
      frequent procedures included direct suture of a lesion, resection and replacement
      of an injured artery or bypass grafting. In 13 patients we used interventional
      radiology procedures (in most cases it was for thoracic endovascular aortic
      repair). In one patient we were able to use a conservative treatment. RESULTS:
      The 30-day mortality rate was 8.5%, i.e., seven patients died of polytrauma. The
      morbidity rate was 35% (29 patients). The most frequent complications included
      respiratory failure in polytrauma (13%), transient leg/arm swelling (6%) and
      wound infection (4%). Primary and secondary graft patencies were 100% and 95.5%,
      respectively. Vascular reconstruction failed in three patients and, in two of
      them, we had to carry out limb amputation. CONCLUSIONS: From the viewpoint of
      vascular surgery, even very serious injuries of upper and lower extremities can
      be managed, if possible associated injuries of the skeletal and nerve structures
      allow for it. The key to success is good co-operation of the orthopaedic trauma
      surgeon, vascular surgeon and neurosurgeon.

PMID- 23140605
TI  - [Odontoid fracture combined with lateral atlanto-axial dislocation. Report of two
      cases].
AB  - The authors describe their experience with treatment of two neurologically intact
      male patients, aged 70 and 74 years, presenting with combined lateral atlanto
      axial dislocation and odontoid type II fracture. The mechanism of these two
      craniovertebral junction injuries had been lateroflexion of the neck. The initial
      attempt at closed reduction using axial traction failed. The authors succeeded
      with a closed reduction maneuver under general anaesthesia in the first patient
      in whom long-term stability was achieved by transarticular C2-C1 fixation,
      together with interlaminar fusion. In the second patient, closed reduction was
      unsuccessful due to intra-articular soft tissue interposition. Release and
      reduction were achieved by instrumentation of C1 lateral masses and
      transpedicular anchorage of screws into the C2. The subsequent Harms C1-C2
      stabilisation proved to be effective both in achieving long-term stability and
      segmental fusion of lateral masses. Aspects of biomechanics as well as a review
      of pertinent literature are presented.

PMID- 23140606
TI  - Reconstruction of posterior auricular ear surface defects: "Ear Keystone graft".

PMID- 23140607
TI  - Plantar reconstruction with free thoracodorsal artery perforator flaps.
AB  - PURPOSE: The plantar region presents unique challenges for reconstructive
      surgeons. Reconstruction using a thoracodorsal artery perforator (TDAP) flap
      yields favourable results in various fields of microsurgical reconstruction, but
      reports on the reconstruction of plantar defects are sparse. Here, the authors
      present their experience in the reconstruction of various defects in the plantar
      region using free TDAP flaps. METHODS: From January 2005 to July 2011, 40 free
      TDAP flaps were transferred for reconstructive purposes to restore skin and soft
      tissue defects in the plantar region. Hospital and outpatient records were
      reviewed independently for all patients. A patient questionnaire including five
      questions was administered to subjectively evaluate reconstructive results.
      RESULTS: A total of 24 male and 16 female patients were enrolled in this study.
      The mean age was 47.8 years and ranged from 7 to 77 years. The most common cause
      of defect was oncology related (n=21), followed by trauma-related (n=11),
      diabetes-related (n=6) and other causes. The average flap size was 63.7 cm2 and
      ranged from 25 to 212 cm2. All flaps survived except for one, resulting in a
      below-knee amputation. The mean follow-up period was 20.4 months. Four patients
      underwent secondary revisional procedures, including simple defatting in two
      patients and excision of redundant skin due to flap instability in two patients.
      The satisfaction surveys were completed by 34 (85%) patients. Patients reported
      high levels of satisfaction in terms of pain, limitation of daily activities,
      donor site satisfaction and overall satisfaction. Most patients were satisfied
      and reported that they would recommend the procedure to others. CONCLUSION: An
      appropriately thinned free TDAP flap with thick skin provided favourable outcomes
      with high patient satisfaction and is a valuable option for the restoration of
      skin and soft-tissue defects in the plantar region.

PMID- 23140608
TI  - Walkabout on the long branches of plant evolution.
AB  - The closest living relatives of land plants, the Charophytes, and early diverging
      land plant lineages, the bryophytes, reside in a phylogenetic grade. Recent
      analyses have resolved relationships and demonstrated that some components of the
      land plant developmental genetic toolkit have their origin in algal ancestors.
      Phylogenetic grades of taxa imply long independent evolutionary histories, with
      extant species diversity potentially relictual and highly derived
      morphologically, making reconstruction of ancestral states problematic.
      Incorporating data on the genetic bases of character states may be
      phylogenetically informative in elucidating ancestral states in cases where
      morphology is highly divergent.

PMID- 23140609
TI  - A 28 nt long synthetic 5'UTR (synJ) as an enhancer of transgene expression in
      dicotyledonous plants.
AB  - BACKGROUND: A high level of transgene expression is required, in several
      applications of transgenic technology. While use of strong promoters has been the
      main focus in such instances, 5'UTRs have also been shown to enhance transgene
      expression. Here, we present a 28 nt long synthetic 5'UTR (synJ), which enhances
      gene expression in tobacco and cotton. RESULTS: The influence of synJ on
      transgene expression was studied in callus cultures of cotton and different
      tissues of transgenic tobacco plants. The study was based on comparing the
      expression of reporter gene gus and gfp, with and without synJ as its 5'UTR.
      Mutations in synJ were also analyzed to identify the region important for
      enhancement. synJ, enhances gene expression by 10 to 50 fold in tobacco and
      cotton depending upon the tissue studied. This finding is based on the
      experiments comparing the expression of gus gene, encoding the synJ as 5'UTR
      under the control of 35S promoter with expression cassettes based on vectors like
      pBI121 or pRT100. Further, the enhancement was in most cases equivalent to that
      observed with the viral leader sequences known to enhance translation like Omega
      and AMV. In case of transformed cotton callus as well as in the roots of tobacco
      transgenic plants, the up-regulation mediated by synJ was much higher than that
      observed in the presence of both Omega as well as AMV. The enhancement mediated
      by synJ was found to be at the post-transcriptional level. The study also
      demonstrates the importance of a 5'UTR in realizing the full potential of the
      promoter strength. synJ has been utilized to design four cloning vectors: pGEN01,
      pBGEN02, pBGEN02-hpt and pBGEN02-ALSdm each of which can be used for cloning the
      desired transgene and achieving high level of expression in the resulting
      transgenic plants. CONCLUSIONS: synJ, a synthetic 5'UTR, can enhance transgene
      expression under a strong promoter like 35S as well as under a weak promoter like
      nos in dicotyledonous plants. synJ can be incorporated as the 5'UTR of
      transgenes, especially in cases where high levels of expression is required. A
      set of vectors has also been designed to facilitate this process.

PMID- 23140611
TI  - Spinal neurofibromatosis in children.

PMID- 23140610
TI  - Exposure to traffic emissions: associations with biomarkers of antioxidant status
      and oxidative damage.
AB  - BACKGROUND: Oxidative stress has been implicated as a possible mechanism for
      adverse health effects associated with traffic emissions. We examined the
      association of an estimate of traffic emissions with blood biomarkers of
      antioxidant capacity (glutathione, glutathione peroxidase, trolox-equivalent
      antioxidant capacity) and oxidative damage (thiobarbituric acid-reactive
      substances (TBARS)) among 1810 healthy women, randomly selected from Erie and
      Niagara Counties in Western New York. METHODS: A geographic traffic emission and
      meteorological dispersion model was used to estimate annual polycyclic aromatic
      hydrocarbon (PAH) exposure from traffic emissions for each woman based on her
      residence at the time of study. Associations of traffic-related PAH exposure with
      measures of oxidative stress and antioxidant capacity were examined in multiple
      regression analyses with adjustment for potential confounders. RESULTS: Higher
      traffic-related PAH exposure was associated with decreased glutathione and
      increased glutathione peroxidase. Stronger associations between traffic-related
      PAH exposure and levels of glutathione and glutathione peroxidase were suggested
      among nonsmoking women without secondhand smoke exposure, especially among
      premenopausal nonsmoking women. Associations were also stronger for measurements
      made in warmer months. CONCLUSIONS: These findings suggest that PAHs or other
      components of traffic emissions may impact anti-oxidative capacity among healthy
      women, particularly premenopausal non-smokers without secondhand smoke exposure.

PMID- 23140613
TI  - Nitric oxide synthase in skeletal muscle fibers of patients with type 2 diabetes.
AB  - There is increasing interest in the role of nitric oxide (NO) in common metabolic
      disorders such as type 2 diabetes (T2D) however, fiber-type specific changes in
      NO synthase (NOS) expression in skeletal muscle of T2D patients remain to be
      elucidated. Here we investigated fiber-type related NOS expression in the Vastus
      lateralis muscle of T2D patients compared with healthy individuals with normal
      glucose tolerance (NGT). Cytophotometrical assay did not reveal any quantitative
      differences between NOS expression in muscles from NGT and T2D subjects. Positive
      NOS immunoreactivity in the V. lateralis of T2D patients was found to be
      associated with fast-oxidative glycolytic (FOG) muscle phenotype. This indicates
      that NOS expression in T2D patients correlates both with skeletal muscle fiber
      type distribution and the activity of oxidative and glycolytic enzymes.

PMID- 23140612
TI  - Pilot randomized trial of hydrocortisone in ventilator-dependent extremely
      preterm infants: effects on regional brain volumes.
AB  - OBJECTIVE: To test the hypothesis that high-risk ventilator-dependent extremely
      low birth weight (birth weight <=1000 g) infants treated with 7 days of
      hydrocortisone will have larger total brain tissue volumes than placebo treated
      infants. STUDY DESIGN: A predetermined sample size of 64 extremely low birth
      weight infants, between 10-21 days old and ventilator-dependent with a
      respiratory index score >=2, were randomized to systemic hydrocortisone (17 mg/kg
      cumulative dose) or saline placebo. Primary outcome was total brain tissue
      volume. Volumetric magnetic resonance imaging was performed at 38 weeks
      postmenstrual age; brain tissue regions were segmented and quantified
      automatically with a high degree of accuracy and 9 structures were segmented
      manually. All analyses of regional brain volumes were adjusted by postmenstrual
      age at magnetic resonance imaging scan. RESULTS: The study groups were similar at
      baseline and 8 infants died in each arm. Unadjusted total brain tissue volume
      (mean +/- SD) in the hydrocortisone (N = 23) and placebo treated infants (N = 21)
      was 272 +/- 40.3 cm(3) and 277.8 +/- 59.1 cm(3), respectively (adjusted mean
      difference: 6.35 cm(3) (95% CI: (-20.8, 32.5); P = .64). Three of the 31
      hydrocortisone treated infants and 5 of the 33 placebo treated infants survived
      without severe bronchopulmonary dysplasia (relative risk 0.62, 95% CI: 0.13,
      2.66; P = .49). No significant differences were noted in prespecified secondary
      outcomes of regional structural volumes or days on respiratory support. No
      adverse effects of hydrocortisone were observed. CONCLUSIONS: Low dose
      hydrocortisone in high-risk ventilator-dependent infants after a week of age had
      no discernible effect on regional brain volumes or pulmonary outcomes prior to
      neonatal intensive care unit discharge.

PMID- 23140614
TI  - Vitamin D deficiency amongst minority ethnic groups in the UK: a cross sectional
      study.
AB  - BACKGROUND: Vitamin D deficiency is common amongst minority groups in Britain but
      its magnitude amongst South Asian (SA) and Black African-Caribbean (AC) groups is
      not well defined. The steroidal, endocrine nature of vitamin D provides it with a
      putative link with cardiovascular disease (CVD), and we hypothesised that
      aberrant levels of this hormone would reflect a heightened risk of CVD in these
      ethnic groups. METHODS: SA (n=1105, 57% male) and AC (n=748, 51% male) were
      recruited as part of a community heart failure study from 20 primary care
      practices, Birmingham, UK. Vitamin D2/D3 levels were measured to determine rates
      of total vitamin D status, which were age/sex adjusted. RESULTS: The majority of
      SAs had severe vitamin D deficiency (42.2%, 95% CI: 39.2-45.1), which was more
      frequent than in AC (12.5%, 10.2-14.9, p<0.001. Vitamin status in SA and AC was
      unrelated to the presence of osteoporosis, and on multivariate analysis of SA,
      vitamin D levels were independently associated with age (beta=0.18, p<0.001),
      haemoglobin (beta=0.12, p=0.002), and negatively with alkaline phosphatase (a
      marker of bone mineralisation, beta=-0.11, p=0.022). Amongst AC, vitamin D was
      independently associated with having ever smoked (beta=-0.13, p=0.006) and
      systolic blood pressure (beta=0.10, p=0.038). CONCLUSIONS: Vitamin D deficiency
      is a frequent biochemical observation amongst minority groups in Britain but the
      clinical significance is unclear, and ethnically specific. A proportionate
      susceptibility to bone disease is not apparent in either minority group.

PMID- 23140615
TI  - Aptamer-capped multifunctional mesoporous strontium hydroxyapatite nanovehicle
      for cancer-cell-responsive drug delivery and imaging.
AB  - A novel cancer-cells-triggered controlled-release gadolinium-doped luminescent
      and mesoporous strontium hydroxyapatite nanorods (designated as Gd:SrHap
      nanorods) system using cell-type-specific aptamers as caps has been constructed.
      Aptamers behave as a dual-functional molecule that acts as not only a lid but
      also a targeted molecular that can be used in an effective way for
      therapeutically special cancer cells. After incubated with cancer cells, for
      example, MCF-7 cells, the doxorubicin-loaded and aptamer-capped Gd:SrHap nanorods
      (designated as Gd:SrHap-Dox-aptamer) can be internalized into MCF-7 cells,
      resulting in the pore opening and drug releasing. Furthermore, the high
      biocompatibility and biodegradability Gd:SrHap nanorods with blue
      autofluorescence and paramagnetism could serve as a good contrast agent of
      targeting fluorescence and magnetic resonance imaging. We envision that this
      Gd:SrHap system could play a significant role in developing new generations of
      site-selective, controlled-release delivery and interactive sensory nanodevices.

PMID- 23140616
TI  - Expression of short peptide by an improved isocaudamer tandem repeat strategy.
AB  - An improved isocaudamer tandem repeat strategy for the production of short
      functional peptide was demonstrated in the study. The coding sequence of short
      peptide was codon optimized, and two isocaudamers were induced into the end of
      coding sequence. By re-cutting with isocaudamers and re-ligating, the coding
      sequence of short peptide in the expression vector was increased in a multiple
      manner (21, 22, 23, 24, 25 .......). In the present study, an 8 amino-acidresidue
      peptide of porcine reproductive and respiratory syndrome virus (PRRSV) was
      effectively expressed in 8 copies and 16 copies by this approach, then the
      proteins in 8 copies and 16 copies were used to generate antibody against this
      epitope in rabbits. The results showed that PRRSVs were well recognized by the
      antibody in indirect immunofluorescence assay. The technology using isocaudamer
      to insert multiple tandem repeats in the vector provides an important approach
      for the studies of small molecule peptides.

PMID- 23140617
TI  - [Delivery in women with previous cesarean section or other uterine surgery:
      guidelines for clinical practice - introduction].

PMID- 23140618
TI  - [Management of post-abortum infections].
AB  - In countries where induced abortions are legal and medically supervised, the
      frequency of post-abortion infections is low and maternal death is infrequent.
      Nevertheless, short and long term consequences of post-abortion infections must
      be addressed. Sexually transmitted pathogens are frequently in cause here. Risk
      factors include in particular young age (less than 24 years), low socioeconomic
      level, late pregnancy, nulliparity, and history of previous untreated pelvic
      inflammatory disease. Diagnosis is based on clinical criteria and an inflammatory
      syndrome occurring within 2 to 3 weeks after spontaneous or induced abortion. A
      pelvic ultrasound is recommended in order to ensure the uterus vacuity and to
      look for a possible pelvic abscess, and bacteriological samples must be
      performed. Management consists in a regimen combining two antibiotics
      intravenously, with the possible addition of intravenous heparin in case of
      pelvic thrombophlebitis. Antibiotics can be discontinued 48 h of a clinical
      improvement and further treatment by oral route brings no benefit. Intrauterine
      retention associated with post-abortion endometritis must be addressed either by
      medical or surgical method.

PMID- 23140619
TI  - [Delivery in women with previous cesarean section or other uterine surgery:
      guidelines for clinical practice - text of the guidelines (short text)].

PMID- 23140620
TI  - [Diagnosis of pelvic inflammatory disease. Which clinical and paraclinical
      criteria? Role of imaging and laparoscopy?].
AB  - Diagnosis of pelvic inflammatory disease is difficult. We focus on a systematic
      literature review to study diagnostic values of history-taking, clinical
      examination, laboratory tests and imagery. After this literature review, we build
      a diagnostic model for pelvic inflammatory disease. This diagnostic model is
      built on two major criteria: presence of adnexal tenderness or cervical motion
      tenderness. Additional minor criteria, increasing the likelihood of the diagnosis
      of pelvic inflammatory disease were added based on their specificity and their
      positive likelihood ratio. These minor criteria are supported by history-taking,
      clinical examination, laboratory tests and also on relevant ultrasonographic
      criteria.

PMID- 23140621
TI  - [Microbiologic basis of diagnosis and treatment of pelvic inflammatory disease].
AB  - Pelvic inflammatory disease (PID) is caused by a large spectrum of micro
      organisms. However, the microbiological cause is unknown in approximately half of
      cases according to varying series. In the context of sexually transmitted disease
      (STD), the most frequently identified microorganisms causing PID are Neisseria
      gonorrhoeae, Chlamydia trachomatis and Mycoplasma genitalium. In such cases,
      bacterial vaginosis and Trichomonas vaginalis are frequently associated. In case
      of complicated PID or when PID is the consequence of delivery, abortion, intra
      uterine procedure, bacteria that come from vaginal carriage may be encountered:
      Enterobacteriacae, Staphylococcus spp., Streptococcus spp., anaerobes. Mycopslama
      hominis as well as Ureaplasma urealyticum may also be found in this context. The
      microbiological diagnosis may be performed on samples of vaginal liquid,
      endocervix or, when available, surgical specimens. The microbiological diagnostic
      procedures that are used to identify these microrgansims are reviewed. Vaginal
      sampling may help to identify N. gonorrhoeae, C. trachomatis and M. genitalium
      using nucleic acid amplification tests (NAAT), and is also of interest because of
      the epidemiological association of PID to bacterial vaginosis and trichomoniasis.
      Samples from the endocervix, and if available, from endometrial biopsy surgical
      procedures, should be processed to detect N. gonorrhoeae, C. trachomatis and M.
      genitalium using NAAT, and to search for the presence of Neisseria gonorrhoeae
      (antibiogram should be performed), facultative anaerobes, anaerobes and
      capnophilic bacteria. The antibiotic treatment should at least cover N.
      gonorrhoeae, C. trachomatis and M. genitalium, and for most of the authors,
      anaerobes. In case, microbiological studies demonstrate the role of other
      bacteria (e.g., Enterobacteriacae), theses should be treated according to the
      results of antibiogram.

PMID- 23140622
TI  - Synthesis, photophysical and photochemical properties of photoacid generators
      based on N-hydroxyanthracene-1,9-dicarboxyimide and their application toward
      modification of silicon surfaces.
AB  - We have introduced a series of nonionic photoacid generators (PAGs) for
      carboxylic and sulfonic acids based on N-hydroxyanthracene-1,9-dicarboxyimide
      (HADI). The newly synthesized PAGs exhibited positive solvachromatic emission
      (lambda(max)(hexane) 461 nm, lambda(max)(ethanol) 505 nm) as a function of
      solvent polarity. Irradiation of PAGs in acetonitrile (ACN) using UV light above
      410 nm resulted in the cleavage of weak N-O bonds, leading to the generation of
      carboxylic and sulfonic acids in good quantum and chemical yields. Mechanism for
      the homolytic N-O bond cleavage for acid generation was supported by time
      dependent density functional theory (TD-DFT) calculations. More importantly,
      using the PAG monomer N-(p-vinylbenzenesulfonyloxy)anthracene-1,9-dicarboxyimide
      (VBSADI), we have synthesized N-(p-vinylbenzenesulfonyloxy)anthracene-1,9
      dicarboxyimide-methyl methacrylate (VBSADI-MMA) and N-(p
      vinylbenzenesulfonyloxy)anthracene-1,9-dicarboxyimide-ethyl acrylate (VBSADI-EA)
      copolymer through atom transfer radical polymerization (ATRP). Finally, we have
      also developed photoresponsive organosilicon surfaces using the aforementioned
      polymers.

PMID- 23140625
TI  - Control of cell polarity and asymmetric division in C. elegans.
AB  - During development of Caenorhabditis elegans, most somatic cells divide
      asymmetrically to produce daughter cells with distinct fates. A Wnt signaling
      pathway called Wnt/beta-catenin asymmetry pathway controls both polarity of
      mother cells and distinct fates of daughter cells. Unlike the PCP pathway that
      regulates cell polarity in other organisms, this Wnt pathway in C. elegans
      requires beta-catenin. However, similar to the PCP pathway, signaling components
      including Dishevelled proteins are asymmetrically localized to the cell cortex. I
      will review current knowledge about the mechanism of this regulation and how the
      orientation of cell polarity is controlled by Wnt proteins.

PMID- 23140623
TI  - The frizzled/stan pathway and planar cell polarity in the Drosophila wing.
AB  - Drosophila has been the key model system for studies on planar cell polarity
      (PCP). The rich morphology of the insect exoskeleton contains many structures
      that display PCP. Among these are the trichomes (cuticular hairs) that cover much
      of the exoskeleton, sensory bristles, and ommatidia. Many genes have been
      identified that must function for the development of normal PCP. Among these are
      the genes that comprise the frizzled/starry night (fz/stan) and dachsous/fat
      pathways. The mechanisms that underlie the function of the fz/stan pathway are
      best understood. All of the protein products of these genes accumulate
      asymmetrically in wing cells and there is good evidence that this involves local
      intercellular signaling between protein complexes on the distal edge of one cell
      and the juxtaposed proximal edge of its neighbor. It is thought that a feedback
      system, directed transport, and stabilizing protein-protein interactions mediate
      the formation of distal and proximal protein complexes. These complexes appear to
      recruit downstream proteins that function to spatially restrict the activation of
      the cytoskeleton in wing cells. This leads to the formation of the array of
      distally pointing hairs found on wings.

PMID- 23140624
TI  - Asymmetric protein localization in planar cell polarity: mechanisms, puzzles, and
      challenges.
AB  - The polarization of epithelial cells along an axis orthogonal to their apical
      basal axis is increasingly recognized for roles in a variety of developmental
      events and physiological functions. While now studied in many model organisms,
      mechanistic understanding is rooted in intensive investigations of planar cell
      polarity (PCP) in Drosophila. Consensus has emerged that two molecular modules,
      referred to here as the global and core modules, operate upstream of effector
      proteins to produce morphological PCP. Proteins of the core module develop
      subcellular asymmetry, accumulating in two groups on opposite sides of cells,
      consistent with proposed functions in producing cell polarity and in
      communicating that polarity between neighboring cells. Less clear are the
      molecular and cell biological mechanisms underlying core module function in the
      generation and communication of subcellular asymmetry and the relationship
      between the global and the core modules. In this review, we discuss these two
      unresolved questions, highlighting important studies and potentially enlightening
      avenues for further investigation. It is likely that results from Drosophila will
      continue to inform our views of the growing list of examples of PCP in vertebrate
      systems.

PMID- 23140626
TI  - Planar cell polarity in coordinated and directed movements.
AB  - Planar cell polarity is a fundamental concept to understanding the coordination
      of cell movements in the plane of a tissue. Since the planar cell polarity
      pathway was discovered in mesenchymal tissues involving cell interaction during
      vertebrate gastrulation, there is an emerging evidence that a variety of
      mesenchymal and epithelial cells utilize this genetic pathway to mediate the
      coordination of cells in directed movements. In this review, we focus on how the
      planar cell polarity pathway is mediated by migrating cells to communicate with
      one another in different developmental processes.

PMID- 23140627
TI  - Planar cell polarity in the inner ear.
AB  - The inner ears of vertebrates represent one of the most striking examples of
      planar cell polarity (PCP). Populations of directionally sensitive mechanosensory
      hair cells develop actin-based stereociliary bundles that are uniformly oriented.
      Analysis of perturbations in bundle polarity in mice with mutations in Vangl2
      formed the basis for the initial demonstration of conservation of the PCP
      signaling pathway in vertebrates. Subsequent studies have demonstrated roles for
      other "core" PCP genes, such as Frizzled, Disheveled, and Celsr, and for
      identifying novel PCP molecules such as Scribble and Ptk7. In addition, the
      demonstration of hearing deficits in humans with mutations in cilia genes
      combined with analysis of PCP defects in mice with ciliary deletion has
      implicated the cilia as an important modulator of hair cell polarization.
      Finally, the presence of shortened cochleae in many PCP mouse mutants has
      revealed an additional role for the PCP pathway in the development of the
      auditory system.

PMID- 23140628
TI  - Does planar cell polarity signaling steer growth cones?
AB  - Recent studies established the role of planar cell polarity signaling in axon
      guidance. Signaling mechanisms controlling the direction of axon growth are
      poorly understood. The possibility that conserved and robust cell polarity
      signaling pathways may be reused as a key mechanism to convey asymmetric
      signaling in growth cones will provide insights to solving this long-standing
      mystery. Insights gained from growth cones can also shed light on general
      principles of cell polarity signaling. This review also discusses the possibility
      that this cell polarity signaling-based mechanism may be a general mechanism for
      mediating directional control by many, if not all, axon guidance molecules.

PMID- 23140629
TI  - Celsr1-3 cadherins in PCP and brain development.
AB  - Cadherin EGF LAG seven-pass G-type receptors 1, 2, and 3 (Celsr1-3) form a family
      of three atypical cadherins with multiple functions in epithelia and in the
      nervous system. During the past decade, evidence has accumulated for important
      and distinct roles of Celsr1-3 in planar cell polarity (PCP) and brain
      development and maintenance. Although the role of Celsr in PCP is conserved from
      flies to mammals, other functions may be more distantly related, with Celsr
      working only with one or a subset of the classical PCP partners. Here, we review
      the literature on Celsr in PCP and neural development, point to several remaining
      questions, and consider future challenges and possible research trends.

PMID- 23140631
TI  - Dishevelled: in vivo roles of a multifunctional gene family during development.
AB  - Dishevelled proteins are highly conserved throughout evolution and participate in
      canonical and noncanonical Wnt pathways. In particular, Dvls participate in the
      planar cell polarity (PCP) pathway that is important for a variety of
      developmental processes. There are three Dvl genes in mammals. These three genes
      are highly conserved and broadly expressed throughout development and in the
      adult. Studies of mice with disruption of a single Dvl gene have revealed
      phenotypes that range from defective social behavior to developmental defects
      that include abnormal heart, skeletal, and cochlear morphogenesis, suggesting
      that each of the Dvl genes had unique functions. However, analysis of double or
      triple Dvl knock-outs revealed novel phenotypes or more severe phenotypes
      displayed by single knock-outs suggesting overlapping or redundant functions of
      these Dvl genes. Most if not all of the phenotypes displayed by the Dvl mutants
      appear to be the result of PCP pathway functions, not of the canonical Wnt
      pathway. This suggests that the PCP pathway is sensitive to reduction of Dvls,
      but only one Dvl allele of six may be required for Wnt pathway.

PMID- 23140632
TI  - An expanding role of Vangl proteins in embryonic development.
AB  - The mammalian Vangl1 and Vangl2 genes were discovered a decade ago through their
      association with neural tube defects, in particular the presence of Vangl2
      mutations in independent alleles of the mouse mutant Loop-tail (Lp), a mouse
      model of the severe neural tube defect craniorachischisis. Vangl1 and Vangl2
      variants have also been detected in familial and sporadic cases of spina bifida.
      Vangl proteins are highly conserved in evolution with relatives in flies, and
      distant invertebrates and vertebrates. In these organisms, they play a central
      role in planar cell polarity (PCP) and convergent extension (CE) movements. Over
      the past decade, these functional characteristics have also been established for
      mammalian Vangl genes. The careful analysis of mouse Vangl genes mutants has
      showed that these genes and the associated PCP pathway and CE movements are
      involved in many unexpected developmental processes, from morphogenesis of
      different tissues, left-right asymmetry, asymmetric cell division, and
      organization of many epithelial structures, as well as positioning and function
      of cellular appendages. Genetic studies in double mutants and biochemical studies
      of interacting proteins have started to elucidate the molecular pathways in which
      Vangl proteins participate and that regulate these complex events.

PMID- 23140630
TI  - The kidney and planar cell polarity.
AB  - Planar cell polarity (PCP) or tissue polarity describes a coordinated polarity at
      the plane of the tissue where most or all cells within a tissue are polarized in
      one direction. It is perpendicular to the apical-basal polarity of the cell. PCP
      is manifested readily in the Drosophila wing and cuticle bristles, Drosophila eye
      ommatidia, and mammalian hair and inner ear hair bundles, and less evidently, in
      cellular processes such as in the coordinated, directional cell movements, and
      oriented cell divisions that are important for tissue morphogenesis. Several
      distinct molecular and cellular processes have been implicated in the regulation
      of PCP. Here, we review potential roles for PCP during mouse kidney development
      and maintenance, including ureteric bud branching morphogenesis, renal medulla
      elongation, tubule diameter establishment/maintenance, glomerulogenesis, and
      response to injury. The potential mechanisms underlying these processes,
      including oriented cell division and coordinated cell migration/cell
      intercalation, are discussed. In addition, we discuss some unaddressed research
      topics related to PCP in the kidney that we hope will spur further discussion and
      investigation.

PMID- 23140633
TI  - Wnt regulation of planar cell polarity (PCP).
AB  - Planar cell polarity (PCP), a process controlling coordinated, uniformly
      polarized cellular behaviors in a field of cells, has been identified to be
      critically required for many fundamental developmental processes. However, a
      global directional cue that establishes PCP in a three-dimensional tissue or
      organ with respect to the body axes remains elusive. In vertebrate, while Wnt
      secreted signaling molecules have been implicated in regulating PCP in a beta
      catenin-independent manner, whether they function permissively or act as a global
      cue to convey directional information is not clearly defined. In addition, the
      underlying molecular mechanism by which Wnt signal is transduced to core PCP
      proteins is largely unknown. In this chapter, I review the roles of Wnt signaling
      in regulating PCP during vertebrate development and update our knowledge of its
      regulatory mechanism.

PMID- 23140634
TI  - Planar cell polarity during development. Preface.

PMID- 23140635
TI  - Diagnostic imaging of pulmonary embolism using endobronchial ultrasound.
AB  - Endobronchial ultrasound (EBUS) is a new technique that can be used for the
      diagnostic imaging of central pulmonary thromboembolism (PE). In eight cases at
      our clinic, EBUS was used because of mediastinal lymphadenopathies or
      paramediastinal nodular lesions and at the same time images were obtained of a PE
      by means of EBUS. The PE was diagnosed before the EBUS with computed tomography
      (CT) of the lungs in all cases (5 women and 3 men). The repletion defects of all
      the cases compatible with a PE were clarified with CT-angiography. EBUS may be an
      alternative method for the diagnosis of PE, as it can indicate the presence of a
      thrombus in the central pulmonary arteries in hemodynamically-stable cases.

PMID- 23140636
TI  - The missing link: Mul1 signals mitophagy and muscle wasting.
AB  - FoxO3 regulates the transcription of autophagy-related genes that induce
      mitophagy in muscle wasting. In this issue of Cell Metabolism, Lokireddy et al.
      (2012) now show that the mitochondrial ubiquitin protein ligase 1 (Mul1)
      polyubiquitinates the mitochondrial fusion protein Mfn2 and is necessary for
      FoxO3- and lysosomal-dependent mitophagy in muscle atrophy.

PMID- 23140637
TI  - Treating diabetes by blocking a vascular growth factor.
AB  - Ectopic lipid deposition in muscle and liver is associated with the pathogenesis
      of type II diabetes. Hagberg et al. (2012) report that targeting the vascular
      endothelial growth factor (VEGF)-B restores insulin sensitivity and glucose
      tolerance by inhibiting endothelial-to-tissue lipid transport, opening promising
      avenues for diabetes therapy.

PMID- 23140638
TI  - Mining genes in type 2 diabetic islets and finding gold.
AB  - Pancreatic beta cell failure is central in the pathogenesis of type 2 diabetes
      (T2D), but the mechanisms involved remain unclear. Mahdi and colleagues (2012)
      couple global evaluation of gene expression with coexpression network analysis of
      human islets from T2D patients to identify SFRP4 as an early mediator of beta
      cell dysfunction in T2D.

PMID- 23140639
TI  - RIPping off GABA release in hypothalamic circuits causes obesity.
AB  - Hypothalamic RIP-expressing neurons regulate energy balance, but the precise
      neural pathways and neurotransmitters mediating this effect remain undetermined.
      Kong et al. (2012) now demonstrate that RIP neurons regulate energy expenditure
      and BAT thermogenesis predominantly via a GABAergic arcuate-paraventricular
      hindbrain pathway.

PMID- 23140640
TI  - Gut microbiota composition and activity in relation to host metabolic phenotype
      and disease risk.
AB  - The symbiotic gut microbiota modulate health and disease of the host through a
      series of transgenomic metabolic and immune regulatory axes. We explore
      connections between microbiome composition and function related to individual
      metabolic phenotypes and consider these interactions as possible targets for
      developing new personalized therapies and clinical management strategies.

PMID- 23140641
TI  - The ubiquitin ligase Mul1 induces mitophagy in skeletal muscle in response to
      muscle-wasting stimuli.
AB  - Recent research reveals that dysfunction and subsequent loss of mitochondria
      (mitophagy) is a potent inducer of skeletal muscle wasting. However, the
      molecular mechanisms that govern the deregulation of mitochondrial function
      during muscle wasting are unclear. In this report, we show that different muscle
      wasting stimuli upregulated mitochondrial E3 ubiquitin protein ligase 1 (Mul1),
      through a mechanism involving FoxO1/3 transcription factors. Overexpression of
      Mul1 in skeletal muscles and myoblast cultures was sufficient for the induction
      of mitophagy. Consistently, Mul1 suppression not only protected against mitophagy
      but also partially rescued the muscle wasting observed in response to muscle
      wasting stimuli. In addition, upregulation of Mul1, while increasing
      mitochondrial fission, resulted in ubiquitination and degradation of the
      mitochondrial fusion protein Mfn2. Collectively, these data explain the molecular
      basis for the loss of mitochondrial number during muscle wasting.

PMID- 23140642
TI  - Secreted frizzled-related protein 4 reduces insulin secretion and is
      overexpressed in type 2 diabetes.
AB  - A plethora of candidate genes have been identified for complex polygenic
      disorders, but the underlying disease mechanisms remain largely unknown. We
      explored the pathophysiology of type 2 diabetes (T2D) by analyzing global gene
      expression in human pancreatic islets. A group of coexpressed genes (module),
      enriched for interleukin-1-related genes, was associated with T2D and reduced
      insulin secretion. One of the module genes that was highly overexpressed in
      islets from T2D patients is SFRP4, which encodes secreted frizzled-related
      protein 4. SFRP4 expression correlated with inflammatory markers, and its release
      from islets was stimulated by interleukin-1beta. Elevated systemic SFRP4 caused
      reduced glucose tolerance through decreased islet expression of Ca(2+) channels
      and suppressed insulin exocytosis. SFRP4 thus provides a link between islet
      inflammation and impaired insulin secretion. Moreover, the protein was increased
      in serum from T2D patients several years before the diagnosis, suggesting that
      SFRP4 could be a potential biomarker for islet dysfunction in T2D.

PMID- 23140643
TI  - Metabolomics identifies an inflammatory cascade involved in dioxin- and diet
      induced steatohepatitis.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is among the most potent
      environmentally toxic compounds. Serum metabolomics identified azelaic acid
      monoesters as significantly increased metabolites after TCDD treatment, due to
      downregulation of hepatic carboxylesterase 3 (CES3, also known as triglyceride
      hydrolase) expression in an arylhydrocarbon receptor (AhR)-dependent manner in
      mice. The decreased CES3 expression was accomplished by TCDD-stimulated TGFbeta
      SMAD3 and IL6-STAT3 signaling, but not by direct AhR signaling. Methionine- and
      choline-deficient (MCD) diet-treated mice also showed enhanced serum azelaic acid
      monoester levels after attenuation of hepatic CES3 expression, while db/db mice
      did not, thus suggesting an association with steatohepatitis. Forced expression
      of CES3 reversed serum azelaic acid monoester/azelaic acid ratios and hepatic
      TGFbeta mRNA levels in TCDD- and MCD diet-treated mice and ameliorated
      steatohepatitis induced by MCD diet. These results support the view that azelaic
      acid monoesters are possible indicators of TCDD exposure and steatohepatitis and
      suggest a link between CES3, TGFbeta, and steatohepatitis.

PMID- 23140644
TI  - Below thermoneutrality, changes in activity do not drive changes in total daily
      energy expenditure between groups of mice.
AB  - In this study we investigated the relationship between activity and energy
      expenditure (EE) in mice. By determining the relationship between activity and EE
      over a 24 hr period in an individual mouse, activity was calculated to account
      for 26.6% +/- 1.1% of total EE at 30 degrees C. However, when comparing across
      multiple mice, only 9.53% +/- 1.1% of EE from activity appeared to be independent
      of other components involved in the thermogenic response, suggesting other
      metabolic processes may mask the contribution of activity to EE. In line with
      this concept, below thermoneutrality mice still expended a substantial amount of
      energy on activity; however, at 24 degrees C, 20 degrees C, or 5 degrees C, no
      independent effect of EE from activity on total daily EE could be detected.
      Overall these results suggest that when studying mice at temperatures below
      thermoneutrality, activity is unlikely to explain differences in EE between
      groups of animals.

PMID- 23140645
TI  - A quantitative map of the liver mitochondrial phosphoproteome reveals
      posttranslational control of ketogenesis.
AB  - Mitochondria are dynamic organelles that play a central role in a diverse array
      of metabolic processes. Elucidating mitochondrial adaptations to changing
      metabolic demands and the pathogenic alterations that underlie metabolic
      disorders represent principal challenges in cell biology. Here, we performed
      multiplexed quantitative mass spectrometry-based proteomics to chart the
      remodeling of the mouse liver mitochondrial proteome and phosphoproteome during
      both acute and chronic physiological transformations in more than 50 mice. Our
      analyses reveal that reversible phosphorylation is widespread in mitochondria,
      and is a key mechanism for regulating ketogenesis during the onset of obesity and
      type 2 diabetes. Specifically, we have demonstrated that phosphorylation of a
      conserved serine on Hmgcs2 (S456) significantly enhances its catalytic activity
      in response to increased ketogenic demand. Collectively, our work describes the
      plasticity of this organelle at high resolution and provides a framework for
      investigating the roles of proteome restructuring and reversible phosphorylation
      in mitochondrial adaptation.

PMID- 23140646
TI  - Marital status, childhood maltreatment, and family dysfunction: a controlled
      study of pathological gambling.
AB  - BACKGROUND: Pathological gambling is a prevalent public health problem associated
      with depression, substance misuse, crime, and suicide. Despite these challenges,
      little attention has been directed to examining its negative consequences on
      families and marriages, including divorce rates, childhood maltreatment, and
      family dysfunction. METHOD: From February 2005 to June 2010, subjects with DSM-IV
      defined pathological gambling and community controls were assessed for marital
      and family variables and indices of childhood maltreatment. The Family Assessment
      Device (FAD) was used to evaluate family functioning. RESULTS: Ninety-five
      subjects with DSM-IV pathological gambling and 91 control subjects without
      pathological gambling were recruited and assessed. They were similar in age,
      gender, and employment status. Persons with pathological gambling were more
      likely than controls to have >= 1 divorce (odds ratio [OR] = 2.56; 95% CI, 1.35
      4.87; P = .004), to live alone (OR = 4.49; 95% CI, 1.97-10.25; P < .001), and to
      report any type of childhood maltreatment (OR = 4.02; 95% CI, 2.12-7.64; P <
      .001). They did not differ on number of siblings or ordinal position among
      siblings. Pathological gambling subjects reported significantly worse family
      functioning than control subjects as assessed by all 7 FAD subscales. On the FAD
      general functioning subscale, 55% of pathological gambling families and 33% of
      control families were rated "unhealthy" (OR = 2.17; 95% CI, 1.14-4.12; P = .018).
      Severity of gambling was positively correlated with divorce, childhood
      maltreatment, and the FAD roles subscale. CONCLUSIONS: People with pathological
      gambling are more likely than controls to have been divorced, to live alone, and
      to report having experienced childhood maltreatment than controls. They also
      report greater family dysfunction.

PMID- 23140647
TI  - Correlation between different levels of placebo response rate and clinical trial
      outcome in major depressive disorder: a meta-analysis.
AB  - OBJECTIVE: To investigate the relationship between specific levels of placebo
      response rates and the drug response rate and the relative risk of response to
      drug versus placebo in clinical trials of antidepressant monotherapy and
      adjunctive polypharmacy for MDD. DATA SOURCES: MEDLINE/PubMed databases were
      searched for studies published in the English language between January 1980 and
      March 2011 by using the search terms depression, placebo, augmentation, adjunct,
      adjunctive, and each of the antidepressant agents identified. The search was
      supplemented by manual bibliographic review and examination of relevant review
      articles. STUDY SELECTION: The analysis included randomized, double-blind,
      placebo-controlled trials of antidepressants used as monotherapy for MDD, 4 weeks
      or longer, and of augmentation/combination treatments for antidepressant partial
      responders/nonresponders with MDD, 1 week or longer. 169 antidepressant
      monotherapy studies and 35 adjunctive polypharmacy studies were found eligible
      for inclusion in our analysis. DATA EXTRACTION: Data extracted included number of
      patients enrolled, patient characteristics, drug dosages and scheme (fixed vs
      flexible dosing), duration of the trial, and response rates. RESULTS: In
      antidepressant monotherapy studies, a higher placebo response rate correlated
      with a lower risk ratio of responding to antidepressant versus placebo (P < .001)
      and correlated with higher antidepressant response rates (P < .001); the number
      needed to treat (NNT) for response was approximately 4, 6, and 9 in trials with
      placebo response rates < 30%, >= 30% and < 40%, and >= 40%, respectively. In
      adjunctive trials, a higher placebo response rate correlated with a lower risk
      ratio of responding to the adjunctive drug versus placebo (P < .001) and
      correlated with a trend toward statistical significance with higher response
      rates to the adjunctive drug (P = .050); the NNT was approximately 6, 7, 11, and
      17 in trials with placebo response rates < 20%, >= 20% and < 30%, >= 30% and <
      40%, and >= 40%, respectively. CONCLUSIONS: These results suggest that the
      relative efficacy of the active drug compared to placebo in clinical trials for
      MDD is highly heterogeneous across studies with different placebo response rates,
      with a worse performance in showing a superiority of the drug versus placebo for
      studies with placebo response rates >= 30% and >= 40%, respectively, for
      monotherapy and adjunctive trials. It is important to maintain placebo response
      rates below this critical threshold, since this is one of the most challenging
      obstacles for new treatment development in MDD.

PMID- 23140648
TI  - Beyond white blood cell monitoring: screening in the initial phase of clozapine
      therapy.
AB  - OBJECTIVE: Clozapine is the preferred option for treatment-resistant
      schizophrenia. However, since 1975, clozapine has been known to cause
      agranulocytosis. In the clozapine screening guidelines, white blood cell count is
      mandatory. In the past 20 years, after its reintroduction, 3 other serious side
      effects, namely, diabetic ketoacidosis, gastrointestinal hypomotility, and
      myocarditis have been documented but have so far failed to be incorporated in the
      screening guidelines. The objective of this review is to determine whether an
      update of the screening guidelines for serious side effects with clozapine is
      evidence based. DATA SOURCES: The English-language literature, available via
      MEDLINE or PubMed, on the incidence of 4 clozapine-related side effects, using
      clozapine, agranulocytosis, diabetic ketoacidosis, and gastrointestinal
      hypomotility as keywords, that have been published over the period 1976-2010, was
      collected. STUDY SELECTION: 16 studies that provided incidence rates or data from
      which these rates could be calculated were included. DATA EXTRACTION: We compared
      1-year incidence rates, mortality rates in the whole study population and in the
      affected cases. When rates reflected longer periods of observation, the given
      rate was recalculated to obtain a 1-year incidence rate. RESULTS: The incidence
      of clozapine-induced agranulocytosis varies between 3.80/00-8.00/00. The
      mortality rate is 0.10/00-0.30/00, and the case-fatality rate is 2.20/00-4.20/00.
      In diabetic ketoacidosis, the incidence was calculated at 1.20/00-3.10/00, and
      the case-fatality rate was 20%-31%. In gastrointestinal hypomotility, the
      incidence was 40/00-80/00, and the case-fatality rate was 15%-27.5%. The
      discrepancy in incidence rates between Australia (70/00-340/00) and the rest of
      the world (0.070/00-0.60/00) impairs a general approach of this side effect.
      CONCLUSIONS: In 2 of the 3 studied side effects, diabetic ketoacidosis and
      gastrointestinal hypomotility, reduction of mortality to the level of
      agranulocytosis is both necessary and feasible. In order to obtain this outcome,
      the screening guidelines need to be modified; early detection of treatment
      emergent hyperglycemia, that might-via diabetes mellitus-develop into diabetic
      ketoacidosis, requires obligatory monthly measurement of fasting plasma glucose.
      To prevent gastrohypomotility, and complications therefrom, the clinician should
      be required to choose between either weekly monitoring or standard coprescription
      of laxatives for prevention. The reported incidence of myocarditis (high in
      Australia, low in the rest of the world) is too divergent to allow for an overall
      recommendation outside Australia.

PMID- 23140649
TI  - Monitoring clozapine adverse effects calls for the integration of protocol and
      good clinical practice.

PMID- 23140650
TI  - There's more to placebo-related improvement than the placebo effect alone.

PMID- 23140651
TI  - More on mood disorders in youth.

PMID- 23140652
TI  - Further evidence for robust familiality of pediatric bipolar I disorder: results
      from a very large controlled family study of pediatric bipolar I disorder and a
      meta-analysis.
AB  - OBJECTIVE: To determine the risk for bipolar I disorder in first-degree relatives
      of children with DSM-IV bipolar I disorder via meta-analysis and expanded
      controlled study. DATA SOURCES AND EXTRACTION: For the meta-analysis, PubMed was
      searched for scientific articles published in the world literature in English
      through 2011. The keywords searched were bipolar disorder, first-degree
      relatives, family study, and control. All online abstracts were reviewed, and
      relevant full manuscripts were collected and reviewed. Citations were also
      examined for other potentially relevant articles. The analysis included only
      controlled family studies that examined rates of bipolar I disorder in all first
      degree relatives (parents and siblings) of pediatric bipolar I probands and that
      had age- and sex-matched controls. Family history studies were excluded, as were
      studies that were not in English, did not report bipolar I rates for all first
      degree relatives, or reported only bipolar spectrum rates. Also excluded were
      family studies that included only adult probands. A meta-analysis was conducted
      of the 5 controlled family studies of pediatric bipolar I probands that met the
      search criteria using the random-effects model of DerSimonian and Laird. METHOD:
      For the family study, our previous sample of DSM-IV bipolar I probands was
      greatly expanded using structured diagnostic interviews. The new study included
      239 children aged 6-17 years who satisfied full DSM-IV diagnostic criteria for
      bipolar I disorder (n = 726 first-degree relatives), 162 attention
      deficit/hyperactivity disorder (ADHD) probands (without bipolar I disorder; n =
      511 first-degree relatives), and 136 healthy control probands (without ADHD or
      bipolar I disorder; n = 411 first-degree relatives). The Kaplan-Meier cumulative
      failure function was used to calculate survival curves and cumulative lifetime
      risk in relatives. Cox proportional hazard models were used to calculate the risk
      of bipolar I disorder in relatives. RESULTS: The pooled odds ratio for bipolar I
      disorder in relatives was estimated to be 6.96 (95% confidence interval [CI], 4.8
      10.1). First-degree relatives of bipolar I probands were also significantly more
      likely than first-degree relatives of both ADHD probands (hazard ratio [HR] =
      3.02; 95% CI, 1.85-4.93; P < .001) and control probands (HR = 2.83; 95% CI, 1.65
      4.84; P < .001) to have bipolar I disorder. CONCLUSIONS: Our results document an
      increased familial risk for bipolar I disorder in relatives of pediatric probands
      with DSM-IV bipolar I disorder.

PMID- 23140653
TI  - Examining the proposed disruptive mood dysregulation disorder diagnosis in
      children in the Longitudinal Assessment of Manic Symptoms study.
AB  - OBJECTIVE: To examine the proposed disruptive mood dysregulation disorder (DMDD)
      diagnosis in a child psychiatric outpatient population. Evaluation of DMDD
      included 4 domains: clinical phenomenology, delimitation from other diagnoses,
      longitudinal stability, and association with parental psychiatric disorders.
      METHOD: Data were obtained from 706 children aged 6-12 years who participated in
      the Longitudinal Assessment of Manic Symptoms (LAMS) study (sample was accrued
      from November 2005 to November 2008). DSM-IV criteria were used, and assessments,
      which included diagnostic, symptomatic, and functional measures, were performed
      at intake and at 12 and 24 months of follow-up. For the current post hoc
      analyses, a retrospective diagnosis of DMDD was constructed using items from the
      K-SADS-PL-W, a version of the Schedule for Affective Disorders and Schizophrenia
      for School-Age Children, which resulted in criteria closely matching the proposed
      DSM-5 criteria for DMDD. RESULTS: At intake, 26% of participants met the
      operational DMDD criteria. DMDD+ vs DMDD- participants had higher rates of
      oppositional defiant disorder (relative risk [RR] = 3.9, P < .0001) and conduct
      disorder (RR = 4.5, P < .0001). On multivariate analysis, DMDD+ participants had
      higher rates of and more severe symptoms of oppositional defiant disorder (rate
      and symptom severity P values < .0001) and conduct disorder (rate, P < .0001;
      symptom severity, P = .01), but did not differ in the rates of mood, anxiety, or
      attention-deficit/hyperactivity disorders or in severity of inattentive,
      hyperactive, manic, depressive, or anxiety symptoms. Most of the participants
      with oppositional defiant disorder (58%) or conduct disorder (61%) met DMDD
      criteria, but those who were DMDD+ vs DMDD- did not differ in diagnostic
      comorbidity, symptom severity, or functional impairment. Over 2-year follow-up,
      40% of the LAMS sample met DMDD criteria at least once, but 52% of these
      participants met criteria at only 1 assessment. DMDD was not associated with new
      onset of mood or anxiety disorders or with parental psychiatric history.
      CONCLUSIONS: In this clinical sample, DMDD could not be delimited from
      oppositional defiant disorder and conduct disorder, had limited diagnostic
      stability, and was not associated with current, future-onset, or parental history
      of mood or anxiety disorders. These findings raise concerns about the diagnostic
      utility of DMDD in clinical populations.

PMID- 23140655
TI  - Cost and cost-effectiveness in a randomized trial of long-acting risperidone for
      schizophrenia.

PMID- 23140654
TI  - Psychological outcomes and predictors of initial weight loss outcomes among
      severely obese adolescents receiving laparoscopic adjustable gastric banding.
AB  - OBJECTIVE: Elevated rates of psychopathology are noted among severely obese youth
      presenting for weight loss surgery. The role of mental health providers in this
      population is not well defined, and the selection of candidates is often the
      result of clinical judgment alone. The purpose of this study was to
      comprehensively evaluate psychiatric symptoms among a large sample of adolescents
      receiving laparoscopic adjustable gastric banding (LAGB) by (1) examining changes
      in depressive symptoms and quality of life in the year following surgery; (2)
      evaluating the interaction between patterns of change in depression, quality of
      life, and weight postsurgery; and (3) identifying presurgical psychological
      predictors of initial weight change. METHOD: Participants were 101 severely obese
      adolescents aged 14 to 18 years receiving LAGB at the Center for Adolescent
      Bariatric Surgery at the Morgan Stanley Children's Hospital of New York
      Presbyterian/Columbia University Medical Center between August 2006 and December
      2009. Measures of height, weight, depressive symptoms, and quality of life were
      obtained in the first year following surgery. Changes in the Beck Depression
      Inventory (BDI), Pediatric Quality of Life Inventory (PedsQL), and body mass
      index were analyzed using latent growth curve modeling. RESULTS: Short-term
      changes in psychiatric symptoms and weight were analyzed using latent growth
      curve modeling. Significant changes in total BDI (betaslope = -0.885, SE = 0.279,
      P < .01; betaquadratic = 0.054, SE = 0.021, P < .001) and PedsQL (betaslope = 
      0.885, SE = 0.279, P < .001) scores were observed following LAGB, and comparable
      postoperative changes between psychosocial variables and body mass index were
      also noted (BDI: covariance [COV] = 0.21, SE = 0.06, P < .001; PedsQL: COV = 
      0.41, SE = 0.10, P < .01). Two variables (family conflict/loss of control eating)
      were found to be significant predictors of weight change over the year following
      surgery (P < .05). CONCLUSIONS: Adolescents experienced notable improvements in
      initial depressive symptoms and quality of life after LAGB, and measures of
      preoperative binge eating and family conflict affected postsurgery body mass
      index among youth. TRIAL REGISTRATION: ClinicalTrials.gov identifier:
      NCT01045499.

PMID- 23140657
TI  - Predictors of suicide in patient charts among patients with depression in the
      Veterans Health Administration health system: importance of prescription drug and
      alcohol abuse.
AB  - OBJECTIVE: To identify factors recorded in electronic medical chart progress
      notes associated with suicide among patients who had received treatment for
      depression. METHOD: The retrospective study sample consisted of 324 randomly
      selected US Veterans Health Administration (VHA) patients treated for depression
      who died by suicide from April 1, 1999, to September 30, 2004, stratified by
      geographic region, gender, and year of depression cohort entry and 312 control
      patients with depression who were alive on the date of suicide death (index date)
      and were from the same stratum as the matched suicide patient. In addition to
      constructing variables from administrative data, variables were abstracted from
      electronic medical chart notes in the year prior to the index date in 5
      categories: clinical symptoms and diagnoses, substance use, life stressors,
      behavioral/ideation measures (eg, suicide attempts), and treatments received.
      Logistic regression was used to assess the associations. RESULTS: Even after we
      adjusted for administratively available data, suicidal behaviors and substance
      related variables were the strongest independent predictors of suicide.
      Prescription drug misuse had an odds ratio (OR) of 6.8 (95% CI, 2.5-18.5);
      history of suicide attempts, 6.6 (95% CI, 1.7-26.4); and alcohol
      abuse/dependence, 3.3 (95% CI, 1.9-5.7). Difficulty with access to health care
      was a predictor of suicide (OR = 2.9; 95% CI, 1.3-6.3). Receipt of VHA substance
      abuse treatment was protective (OR = 0.4; 95% CI, 0.1-0.9). CONCLUSIONS:
      Prescription drug and alcohol misuse assessments should be prioritized in suicide
      assessments among depressed patients. Additionally, behavioral measures noted in
      electronic chart records may be useful in health system monitoring and
      surveillance and can potentially be accessed using word search or natural
      language processing approaches.

PMID- 23140658
TI  - Polymorphisms and haplotypes in the YWHAE gene increase susceptibility to bipolar
      disorder in Chinese Han population.
AB  - BACKGROUND: Schizophrenia and bipolar disorder are 2 major psychiatric illnesses
      sharing some specific genetic risk factors. Increasing evidence suggests the 2
      illnesses might be more closely related than previously considered. OBJECTIVE: To
      test this hypothesis, we investigated the allele and genotype frequencies of 11
      single nucleotide polymorphisms (SNPs) and the haplotypes in these SNPs of the
      YWHAE gene. METHOD: 1,982 patients were interviewed by 2 independent, experienced
      psychiatrists. Bipolar disorder diagnoses were made in strict accordance with
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)
      criteria using the Structured Clinical Interview for DSM-IV Axis I Disorders. In
      2011, we conducted this genetic association analysis between 11 SNPs in YWHAE and
      bipolar disorder, involving a male group and a female group. RESULTS: In the
      analysis of allele and genotype frequencies, the SNP rs1873827 increased
      susceptibility to bipolar disorder in the male group. The haplotype analysis of
      CAC in rs3752826, rs2131431, and rs1873827 in the male group (chi2 = 25.744, P =
      3.97E-07, OR = 0.478 [95% CI, 0.358-0.639]) and of ACT and CAC in rs3752826,
      rs2131431, and rs1873827 in the female group (for ACT, chi2 = 30.365, P = 3.67E
      08, OR = 0.040 [95% CI, 0.007-0.218]; for CAC, chi2 = 16.874, P = 4.04E-05, OR =
      0.597 [95% CI, 0.466-0.765]) showed they are protective factors for bipolar
      disorder. However, the haplotype analysis of CAT in the male group (chi2 =
      19.874, P = 8.39E-06, OR = 2.314 [95% CI, 1.587-3.374]) and of AAC and CAT in the
      female group (for AAC, chi2 = 38.561, P = 5.47E-10, OR = 7.104 [95% CI, 3.471
      14.540]; for CAT, chi2 = 25.497, P = 4.52E-07, OR = 2.076 [95% CI, 1.556-2.770])
      showed they are risk factors for bipolar disorder. CONCLUSIONS: Considering the
      size of our sample, the results suggest that YWHAE does play a major role in
      bipolar disorder in the Han Chinese population.

PMID- 23140659
TI  - Depression epidemiology and its treatment evolution.
AB  - Approximately 1 in 5 US adults have at least one episode of major depression in
      their lifetime. Of those who do, the majority will relapse over the long term and
      many will have psychosocial disabilities and reduced functioning. Over the past
      century, a range of medications have been developed to treat depression, although
      some effective medications have been superseded by newer treatments with an
      improved safety and tolerability profile. A reconsideration of some older
      medications is warranted until agents with truly novel mechanisms of action and
      good safety and tolerability profiles are available.

PMID- 23140660
TI  - When pressure is positive: a literature review of the prehospital use of
      continuous positive airway pressure.
AB  - BACKGROUND: Heart failure poses a significant burden of disease, resulting in
      2,658 Australian deaths in 2008, and listed as an associated cause of death in a
      further 14,466 cases. Common in the hospital setting, continuous positive airway
      pressure (CPAP) therapy is a non-invasive ventilation technique used to prevent
      airway collapse and manage acute pulmonary edema (APO). In the hospital setting,
      CPAP has been known to decrease the need for endotracheal intubation in patients
      with APO. Therefore the objective of this literature review was to identify the
      effectiveness of CPAP therapy in the prehospital environment. METHODS: A review
      of selected electronic medical databases (Cochrane, Medline, EMBASE, and CINAHL)
      was conducted from their commencement date through the end of May 2012. Inclusion
      criterion was any study type reporting the use of CPAP therapy in the prehospital
      environment, specifically in the treatment of heart failure and acute pulmonary
      edema. References of relevant articles were also reviewed. RESULTS: The
      literature search located 1,253 articles, 12 of which met the inclusion criteria.
      The majority of studies found that the use of CPAP therapy in the prehospital
      environment is associated with reduced short-term mortality as well as reduced
      rates of endotracheal intubation. Continuous positive airway pressure therapy was
      also shown to improve patient vital signs during prehospital transport and reduce
      myocardial damage. DISCUSSION: The studies conducted of prehospital use of CPAP
      to manage APO have all demonstrated improvement in patient outcomes in the short
      term. CONCLUSION: Available evidence suggests that the use of CPAP therapy in the
      prehospital environment may be beneficial to patients with acute pulmonary edema
      as it can potentially decrease the need for endotracheal intubation, improve
      vital signs during transport to hospital, and improve short-term mortality.

PMID- 23140661
TI  - Effects of zinc supplementation on antioxidant status and lipid peroxidation in
      hemodialysis patients.
AB  - OBJECTIVES: This study was designed to determine the effects of zinc
      supplementation on oxidative stress in hemodialysis (HD) patients through
      evaluating total antioxidant capacity (TAC), whole blood glutathione peroxidase
      (GSH) level, superoxide dismutase (SOD) activity, and malondialdehyde (MDA)
      level. DESIGN AND SETTING: Double-blinded randomized controlled trialfrom October
      2006 to December 2007 at Tabriz Imam Khomeini Hospital. SUBJECTS: Sixty-five HD
      patients were randomly enrolled into 2 groups. INTERVENTION: Patients received
      placebo in group A and zinc (100 mg/day) in group B for 2 months. After a washout
      period for 2 months, the groups were crossed over and the study was continued for
      an additional 2 months. MAIN OUTCOME MEASURES: Serum zinc concentration was
      measured using atomic absorption spectrophotometry. TAC, GSH level, and SOD
      activity were determined by commercial enzyme-linked immunosorbent assay kits.
      MDA level was measured using a thiobarbituric acid method. RESULTS: The levels of
      serum zinc, TAC, GSH (P < .001 for all), and SOD activity (P < .001 for group A
      and P = .003 for group B) significantly increased after zinc supplementation
      whereas the serum level of MDA decreased after the same period (P = .003 for
      group A and P < .001 for group B). CONCLUSIONS: Zinc supplementation for 2 months
      improved the serum levels of zinc, antioxidant status, and lipid peroxidation in
      HD patients.

PMID- 23140662
TI  - Crystal ball: fluorescence in situ hybridization in the age of super-resolution
      microscopy.
AB  - Super-resolution microscopy encompasses a suite of cutting edge microscopy
      methods able to surpass the resolution limits of light microscopy. The recent
      commercial availability of super-resolution microscopy is advancing many fields
      of biology. In this crystal ball forward look, we briefly examine the
      perspectives of combining super-resolution microscopy and fluorescence in situ
      hybridization (FISH). We strongly believe, based on first evidence presented
      here, that using super-resolution microscopy in environmental microbiology has
      the potential to reshape the way we analyze the results obtained with FISH, by
      improving both the localization and quantification of target molecules.

PMID- 23140663
TI  - Dopamine D2 receptor antagonism suppresses tau aggregation and neurotoxicity.
AB  - BACKGROUND: Tauopathies, including Alzheimer's disease and frontotemporal
      dementia, are diseases characterized by the formation of pathological tau protein
      aggregates in the brain and progressive neurodegeneration. Presently no effective
      disease-modifying treatments exist for tauopathies. METHODS: To identify drugs
      targeting tau neurotoxicity, we have used a Caenorhabditis elegans model of
      tauopathy to screen a drug library containing 1120 compounds approved for human
      use for the ability to suppress tau-induced behavioral effects. RESULTS: One
      compound, the typical antipsychotic azaperone, improved the motility of tau
      transgenic worms, reduced levels of insoluble tau, and was protective against
      neurodegeneration. We found that azaperone reduces insoluble tau in a human cell
      culture model of tau aggregation and that other antipsychotic drugs
      (flupenthixol, perphenazine, and zotepine) also ameliorate the effects of tau
      expression in both models. CONCLUSIONS: Reduction of dopamine signaling through
      the dopamine D2 receptor with the use of gene knockouts in Caenorhabditis elegans
      or RNA interference knockdown in human cell culture has similar protective
      effects against tau toxicity. These results suggest dopamine D2 receptor
      antagonism holds promise as a potential neuroprotective strategy for targeting
      tau aggregation and neurotoxicity.

PMID- 23140664
TI  - Early-life insults impair parvalbumin interneurons via oxidative stress: reversal
      by N-acetylcysteine.
AB  - BACKGROUND: A hallmark of the pathophysiology of schizophrenia is a dysfunction
      of parvalbumin-expressing fast-spiking interneurons, which are essential for the
      coordination of neuronal synchrony during sensory and cognitive processing.
      Oxidative stress as observed in schizophrenia affects parvalbumin interneurons.
      However, it is unknown whether the deleterious effect of oxidative stress is
      particularly prevalent during specific developmental time windows. METHODS: We
      used mice with impaired synthesis of glutathione (Gclm knockout [KO] mice) to
      investigate the effect of redox dysregulation and additional insults applied at
      various periods of postnatal development on maturation and long-term integrity of
      parvalbumin interneurons in the anterior cingulate cortex. RESULTS: A redox
      dysregulation, as in Gclm KO mice, renders parvalbumin interneurons but not
      calbindin or calretinin interneurons vulnerable and prone to exhibit oxidative
      stress. A glutathione deficit delays maturation of parvalbumin interneurons,
      including their perineuronal net. Moreover, an additional oxidative challenge in
      preweaning or pubertal but not in young adult Gclm KO mice reduces the number of
      parvalbumin-immunoreactive interneurons. This effect persists into adulthood and
      can be prevented with the antioxidant N-acetylcysteine. CONCLUSIONS: In Gclm KO
      mice, early-life insults inducing oxidative stress are detrimental to immature
      parvalbumin interneurons and have long-term consequences. In analogy, individuals
      carrying genetic risks to redox dysregulation would be potentially vulnerable to
      early-life environmental insults, during the maturation of parvalbumin
      interneurons. Our data support the need to develop novel therapeutic approaches
      based on antioxidant and redox regulator compounds such as N-acetylcysteine,
      which could be used preventively in young at-risk subjects.

PMID- 23140666
TI  - Psychometric testing of an Arabic version of the Illness Perception Questionnaire
      for heart disease.
AB  - OBJECTIVES: Illness perceptions about heart disease may influence related health
      behaviors. The purpose of this study was to test the psychometric properties of
      an Arabic version of the Illness Perception Questionnaire (IPQ) for heart
      disease. METHODS: Secondary analysis of interview data collected from 401
      visitors of hospital patients in Lebanon was conducted, using an Arabic version
      of the IPQ. Statistical analysis included Cronbach's alpha coefficient,
      correlational and factor analyses. RESULTS: Content validity was supported, with
      a content validity index of 1. The timeline, control and consequences items
      loaded on four factors, explaining 41.6% of the variance. Two factors, internal
      and external, explained 14.54% and 28.36% of the variance in the causes scale.
      The overall Cronbach alpha was .80. CONCLUSIONS: The factor structure did not
      concur with prior findings on the IPQ; no distinct control factor was obtained.
      The type of sample and cultural considerations may explain these findings.
      Replication of this study in Lebanese cardiac patients and further psychometric
      testing in healthy adults are recommended.

PMID- 23140667
TI  - T-wave window adjustment for the determination of microvolt T-wave alternans for
      all patients?

PMID- 23140668
TI  - Use of surface plasmon resonance to investigate lateral wall deposition kinetics
      and properties of polydopamine films.
AB  - Dopamine (DA) is a particularly important neurotransmitter. Polydopamine (pDA)
      films have been demonstrated to be important materials for the immobilization of
      biomolecules onto almost any type of solid substrate. In this study, a surface
      plasmon resonance (SPR)-based sensor system with the sensor chip surface parallel
      to the direction of gravity was used to investigate the lateral wall deposition
      kinetics and properties of pDA films. The deposition kinetics of pDA Films are
      limited by the oxidation process. The pDA film could not be removed from the
      sensor chip completely by a strongly alkaline solution, indicating that the pDA
      film was heterogeneous in the direction of deposition. The pDA film formed near
      the interior of the solution was less stable than the film formed near the gold
      solution interface. Adsorption of proteins on pDA film was studied compared with
      that on bare gold and dextran sensor chip. The reduction of Au(111) cations by
      the pDA film, forming a layer of gold particles, was monitored using SPR.

PMID- 23140665
TI  - Unique signaling profiles of positive allosteric modulators of metabotropic
      glutamate receptor subtype 5 determine differences in in vivo activity.
AB  - BACKGROUND: Metabotropic glutamate receptor subtype 5 (mGlu5) activators have
      emerged as a novel approach to the treatment of schizophrenia. Positive
      allosteric modulators (PAMs) of mGlu5 have generated tremendous excitement and
      fueled major drug discovery efforts. Although mGlu5 PAMs have robust efficacy in
      preclinical models of schizophrenia, preliminary reports suggest that these
      compounds may induce seizure activity. Prototypical mGlu5 PAMs do not activate
      mGlu5 directly but selectively potentiate activation of mGlu5 by glutamate. This
      mechanism may be critical to maintaining normal activity-dependence of mGlu5
      activation and achieving optimal in vivo effects. METHODS: Using specially
      engineered mGlu5 cell lines incorporating point mutations within the allosteric
      and orthosteric binding sites, as well as brain slice electrophysiology and in
      vivo electroencephalography and behavioral pharmacology, we found that some mGlu5
      PAMs have intrinsic allosteric agonist activity in the absence of glutamate.
      RESULTS: Both in vitro mutagenesis and in vivo pharmacology studies demonstrate
      that VU0422465 is an agonist PAM that induces epileptiform activity and
      behavioral convulsions in rodents. In contrast, VU0361747, an mGlu5 PAMs
      optimized to eliminate allosteric agonist activity, has robust in vivo efficacy
      and does not induce adverse effects at doses that yield high brain
      concentrations. CONCLUSIONS: Loss of the absolute dependence of mGlu5 PAMs on
      glutamate release for their activity can lead to severe adverse effects. The
      finding that closely related mGlu5 PAMs can differ in their intrinsic agonist
      activity provides critical new insights that is essential for advancing these
      molecules through clinical development for treatment of schizophrenia.

PMID- 23140669
TI  - [Pulmonary silicoproteinosis. A case of prolonged survival].
AB  - Alveolar silicoproteinosis is a very rare form of silicosis that can develop
      after a latency period of between a few months and 5 years after the first
      exposure to silica, and courses invariably, with rapid deterioration of lung
      function, without an effective response to treatment. Because of its rarity and
      its unique outcome, the case is presented of a 55 year old woman, diagnosed with
      alveolar silicoproteinosis in our hospital, who improved by removing the
      occupational exposure to silica dust and remains stable with no radiological or
      lung function worsening four years after diagnosis of the disease. To our
      knowledge, this is the first case of alveolar silicoproteinosis that had a good
      outcome.

PMID- 23140670
TI  - [Bioprosthesis dysfunction as a presentation form of Coxiella burnettii
      endocarditis].

PMID- 23140672
TI  - DISC1 (disrupted-in-schizophrenia 1) is associated with cortical grey matter
      volumes in the human brain: a voxel-based morphometry (VBM) study.
AB  - DISC1 (Disrupted-In-Schizophrenia 1), one of the top candidate genes for
      schizophrenia, has been associated with a range of major mental illnesses over
      the last two decades. DISC1 is crucially involved in neurodevelopmental processes
      of the human brain. Several haplotypes and single nucleotide polymorphisms of
      DISC1 have been associated with changes of grey matter volumes in brain regions
      known to be altered in schizophrenia and other psychiatric disorders. The aim of
      the present study was to investigate the effects of two single nucleotide
      polymorphisms (SNPs) of DISC1 on grey matter volumes in human subjects using
      voxel-based morphometry (VBM). 114/113 participating subjects (psychiatric
      patients and healthy controls) were genotyped with respect to two at-risk SNPs of
      DISC1, rs6675281 and rs821616. All participants underwent structural magnetic
      resonance imaging (MRI). MRI data was statistically analyzed using voxel-based
      morphometry. We found significant alterations of grey matter volumes in
      prefrontal and temporal brain regions in association with rs6675281 and rs821616.
      These effects of DISC1 polymorphisms on brain morphology provide further support
      for an involvement of DISC1 in the neurobiology of major psychiatric disorders
      such as schizophrenia.

PMID- 23140671
TI  - Brain-derived neurotrophic factor (BDNF) Val66Met and adulthood chronic stress
      interact to affect depressive symptoms.
AB  - BACKGROUND: BDNF Val66Met by chronic stress interaction has been studied using
      childhood stress as a moderator, but has not been widely studied using chronic
      stress in adulthood. METHODS: Two independent samples were used: Duke-CG (238
      Caucasians) and MESA (5524 Caucasians, African Americans and Hispanics). Chronic
      stress in Duke-CG was operationalized as having primary caregiving responsibility
      for a spouse or relative with diagnosed Alzheimer's disease or other major
      dementia; chronic stress in MESA was defined using chronic burden score
      constructed from self-reported problems of health (self and someone close), job,
      finance and relationships. CES-D scale was the measure of depression in both
      samples. The BDNF Val66Met by adulthood chronic stress interaction predicting CES
      D was examined using linear regression, adjusted for covariates. RESULTS: The
      main effect of BDNF Val66Met genotype on CES-D scores was non-significant (ps >
      0.607) but the adulthood chronic stress indicator was significant (ps < 0.001) in
      both samples. The BDNF Val66Met genotype by adulthood chronic stress interaction
      was also significant (ps < 0.039) in both samples. The impact of chronic stress
      in adulthood on CES-D scores was significantly larger in Val/Val genotype
      individuals than Met carriers. CONCLUSION: We found in two independent samples
      that depression levels increased significantly more as a function of adulthood
      chronic stress Val/Val genotype carriers than Met carriers. Individuals with the
      Val/Val genotype and chronic stress exposure could be targeted for interventions
      designed to reduce risk of depression if this finding is confirmed in future
      studies.

PMID- 23140673
TI  - Haptoglobin: the hemoglobin detoxifier in plasma.
AB  - Hemoglobin (Hb) is one of the most studied proteins. However, oxidative toxicity
      associated with free Hb in circulation and its contribution to inflammation and
      complications of transfusion have only recently become active areas of research.
      New insights into the protective mechanisms of haptoglobin (Hp), a plasma
      protein, and a timely resolution of the crystal structure of the Hb-Hp complex
      made it possible to definitively link the functional and structural interplay
      between the two proteins. Here, we summarize current knowledge of the
      interactions between Hb and Hp under oxidative stress conditions, and how Hb's
      own damaging radicals are harnessed by complex formation. Potential therapeutic
      benefits of using Hp for inactivation and clearance of free Hb under a number of
      clinical settings are considered.

PMID- 23140674
TI  - May stroke cause a Complex Sleep Apnea-CompSA?

PMID- 23140675
TI  - Processing of an ultrafine-grained titanium by high-pressure torsion: an
      evaluation of the wear properties with and without a TiN coating.
AB  - A commercial purity (CP) Grade 2 Ti was processed by high-pressure torsion (HPT)
      using an imposed pressure of 3.0GPa at room temperature. The HPT processing
      reduced the grain size from ~8.6 MUm in the as-received state to ultra-fine
      grains (UFG) of ~130 nm after HPT. Tensile testing showed the HPT-processed Ti
      exhibited a good combination of high ultimate tensile strength (~940 MPa) and a
      reasonable elongation to failure (~23%). Physical vapour deposition was used to
      deposit TiN coatings, with a thickness of 2.5 MUm, on Ti samples both with and
      without HPT processing. Scratch tests showed the TiN coating on UFG Ti had a
      critical failure load of ~22.5 N whereas the load was only ~12.7 N for the coarse
      grained Ti. The difference is explained using a simple composite hardness model.
      Wear tests demonstrated an improved wear resistance of TiN coating when using UFG
      Ti as the substrate. The results suggest that CP Ti processed by HPT and
      subsequently coated with TiN provides a potentially important material for use in
      bio-implants.

PMID- 23140676
TI  - Antioxidant enzyme activities and antioxidant capacity in longissimus muscle from
      bulls fed diets rich in polyunsaturated fatty acids.
AB  - The effect of a treatment diet composed of grass silage and concentrate including
      rapeseed (with/without feeding restriction) was compared with a control diet of
      maize silage/grass silage (70:30) and concentrate including soybean, on the
      antioxidant enzyme activities of fresh longissimus muscle from German Simmental
      bulls. Additionally, the effect of diet on antioxidant capacity (AOC) of
      hydrophilic and lipophilic antioxidants was evaluated in fresh and stored beef
      muscle using the FRAP-ferric reducing ability and TEAC - Trolox-equivalent
      antioxidant capacity assays at different reaction times. Catalase and superoxide
      dismutase activities were significantly higher in the treatment diet groups, and
      glutathione peroxidase activity was not different. AOC was not affected by the
      diet. However, storage affected the values of FRAP and TEAC assays, and the
      results were time-depending. 30min were found like a minimum reaction time for
      both assays. Generally, AOC values of the hydrophilic antioxidants were
      significantly higher than lipophilic values.

PMID- 23140677
TI  - A potential probiotic culture ST2 produces siderophore 2,3-dihydroxybenzoylserine
      under intestinal conditions.
AB  - The aim of this study was to characterise siderophores of a culture bearing
      better probiotic qualities of human origin. In this direction, bacterial strain
      ST2 was isolated from faecal sample of 6-month-old healthy infant, which showed
      close similarity with Escherichia coli based on 16S r-RNA gene sequence analysis
      and biochemical characteristics. It was tested for siderophore production under
      in vitro iron limiting intestinal conditions. The siderophore produced was
      catecholate type of 2,3-dihydroxybenzoylserine on the basis of FTIR, NMR and mass
      spectra analysis. The strain obeyed probiotic properties as per WHO and FAO
      guidelines. It showed excellent tolerance in partially simulated gastro
      intestinal tract conditions, non-haemolytic nature, susceptibility to many
      antibiotics tested and antimicrobial activity against enteric pathogens like
      Salmonella typhimurium, Streptococcus pyogenes, and Staphylococcus aureus. Hence,
      this culture could be a possible probiotic candidate in iron nutrition, but only
      after conducting proper animal and human trials.

PMID- 23140678
TI  - Chemical composition and biological activity of Citrus jambhiri Lush.
AB  - The fresh peel of Citrus jambhiri was extracted with aqueous methanol and the
      residue was fractionated using light petroleum, chloroform and ethyl acetate. The
      constituents of the extracts were separated by column chromatography employing
      solvents of different polarity. The chemical structure of the isolated compounds
      was then identified by MS and NMR. Column chromatography of the petroleum
      fraction resulted in the isolation of nobiletin, 5-O-demethylnobiletin,
      tangeretin, 5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone, 3,5,6,7,8,3',4'
      heptamethoxyflavone, and a mixture of beta-sitosterol and stigmasterol. The
      chloroform fraction afforded 6-demethoxynobiletin, 5,4'-dihydroxy-6,7,8,3'
      tetramethoxyflavone, limonin and nomilin. The flavonoid glycosides naringin,
      hesperidin and neohesperidin were isolated from the ethyl acetate fraction. The
      chemical structure of the isolated compounds was established by MS and NMR (APT,
      COSY, HSQC, HMBC, and NOESY). LC-ESI-MS analysis of the ethyl acetate fraction
      afforded eight flavonoid glycosides, while the dichloromethane fraction of the
      defatted seeds contained seven limonoid aglycones. The chloroform fraction
      exerted the strongest DPPH(*) free radical scavenging activity in comparison to
      other fractions. The petroleum fraction showed a significant inhibition of
      lipoxygenase indicating an anti-inflammatory action (IC(50) 29+/-1MUg/mL). Some
      of the isolated polymethoxyflavones exhibited strong cytotoxicity against COS7,
      HeLa and Caco-2 cell lines.

PMID- 23140679
TI  - Antiproliferative, proapoptotic and morphogenic effects of the flavonoid rutin on
      human glioblastoma cells.
AB  - In this study, we investigated the effects of the flavonoid rutin (3,3',4',5,7
      pentahydroxyflavone-3-rutinoside) on glioma cells, using the highly proliferative
      human cell line GL-15 as a model. We observed that rutin (50-100MUM) reduced
      proliferation and viability of GL-15 cells, leading to decreased levels of ERK1/2
      phosphorylation (P-ERK1/2) and accumulation of cells in the G2 phase of the cell
      cycle. On the other hand, 87.4% of GL-15 cells exposed to 100MUM rutin entered
      apoptosis, as revealed by flow cytometry after AnnexinV/PI staining. Nuclear
      condensation and DNA fragmentation were also observed, further confirming that
      apoptosis had occurred. Moreover, the remaining cells that were treated with
      50MUM rutin presented a morphological pattern of astroglial differentiation in
      culture, characterised by a condensed cell body and thin processes with
      overexpression of GFAP. Because of its capacity to induce differentiation and
      apoptosis in cultured human glioblastoma cells, rutin could be considered as a
      potential candidate for malignant gliomas treatment.

PMID- 23140680
TI  - Characterisation of a new antihypertensive angiotensin I-converting enzyme
      inhibitory peptide from Pleurotus cornucopiae.
AB  - This study describes the characterisation of a new angiotensin I-converting
      enzyme (ACE) inhibitory peptide from the fruiting body of Pleurotus cornucopiae
      which could be used as a functional food or nutraceutical compounds. After
      purification of the ACE inhibitor in an ultrafiltration, Sephadex G-25 column
      chromatography, successively C(18) and SCX solid-phase extraction and reverse
      phase HPLC, two types of the purified ACE inhibitors with IC(50) values of 0.46
      and 1.14mg/ml were obtained. The two purified ACE inhibitors were analysed,
      showing two types of oligopeptides. The amino acid sequences of the two purified
      oligopeptides were found to be RLPSEFDLSAFLRA and RLSGQTIEVTSEYLFRH. The
      molecular mass of the purified ACE inhibitors was estimated to be 1622.85 and
      2037.26Da, respectively. Water extracts of P. cornucopiae fruiting body showed a
      clear antihypertensive effect on spontaneously hypertensive rats at a dosage of
      600mg/kg.

PMID- 23140681
TI  - In vitro scavenging capacity of annatto seed extracts against reactive oxygen and
      nitrogen species.
AB  - Bixa orellana L. (annatto), from Bixaceae family, is a native plant of tropical
      America, which accumulates several carotenoids (including bixin and norbixin),
      terpenoids, tocotrienols and flavonoids with potential antioxidant activity. In
      the present study, the in vitro scavenging capacity of annatto seed extracts
      against reactive oxygen species (ROS) and reactive nitrogen species (RNS) was
      evaluated and compared to the bixin standard. Annatto extracts were obtained
      using solvents with different polarities and their phenolic compounds and bixin
      levels were determined by high performance liquid chromatography coupled to diode
      array detector. All annatto extracts were able to scavenge all the reactive
      species tested at the low MUg/mL range, with the exception of superoxide radical.
      The ethanol:ethyl acetate and ethyl acetate extracts of annatto seeds, which
      presented the highest levels of hypolaetin and bixin, respectively, were the
      extracts with the highest antioxidant capacity, although bixin standard presented
      the lowest IC(50) values.

PMID- 23140682
TI  - Influence of the phenophase on the phenolic profile and antioxidant properties of
      Dalmatian sage.
AB  - This study aimed to research the influence of phenophase on the phenolic profile
      (phenolic acids, flavonoids and stilbenes) and related antioxidant properties of
      sage, one of the most characteristic plants of Dalmatian karst. The total phenol
      and flavonoid contents in sage leaves were determined spectrophotometrically,
      while the principal phenolics were determined using HPLC-RP-DAD. Antioxidant
      properties of this well known medicinal plant were determined as free radical
      scavenging activity (DPPH), ferric reducing/antioxidant power (FRAP) and by
      Briggs-Rauscher oscillating reaction (BR). The results strongly indicate that
      Dalmatian sage leaves are rich source of valuable phenolics, mainly phenolic
      acids, with extremely good antioxidant properties. The presence of resveratrol or
      its derivatives was confirmed in all extracts. The best results for total phenols
      and flavonoids, as well as the best antioxidant properties were obtained for May
      sage, while the highest amounts of catechin monomers and compounds from group of
      stilbenes were found in February extract.

PMID- 23140683
TI  - Antioxidant and immunobiological activity of water-soluble polysaccharide
      fractions purified from Acanthopanax senticosu.
AB  - A water-soluble polysaccharide obtained from Acanthopanax senticosus leaves
      (ASL), was fractionated by DEAE-Sepharose fast-flow column chromatography, and
      purified by Sephadex G-75 gel-permeation column chromatography. The
      characteristics of ASP-2-1 were determined by chemical analysis, high-performance
      capillary electrophoresis (HPCE), high-performance gel-permeation chromatography
      (HPGPC). The results show that ASP-2-1 contained 89.47% carbohydrate, 7.45%
      uronic acid, 2.16% protein and seven kinds of monosaccharides including rhamnose,
      xylose, glucose, mannose, arabinose, galactose and glucuronic acid in a molar
      ratio of 7.45:18.63:25.15:0.93:8.35:2.79:5.69, with an average molecular weight
      of about 14,573Da. Furthermore, the immunobiological and antioxidant activities,
      in vitro, of ASP-2-1 were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide) assay and ferric-reducing antioxidant power assay
      (FRAP), 2,2-diphenyl-1-picrylhydrazyl (DPPH()), superoxide radical (()O(2)(-))
      and hydroxyl radical (()OH) free radical-scavenging assay, respectively. The
      results showed that ASP-2-1 exhibited significantly higher immunomodulatory
      activities against the lymphocyte proliferation in vitro, pronounced reductive
      power (FRAP value: 785.1MUM at 0.2mg/ml), strong hydroxyl radical (89.56% at
      1mg/ml) scavenging activity, moderate superoxide radicals (65.32% at 1mg/ml) and
      DPPH radicals (68.9% at 1mg/ml) scavenging activities. ASP-2-1 should be explored
      as a novel and potential natural antioxidant and immunostimulating agent for use
      in functional foods or medicine.

PMID- 23140684
TI  - Amino acid uptake by wild and commercial yeasts in single fermentations and co
      fermentations.
AB  - Musts require nitrogen-containing compounds in order to ensure yeast development.
      This study examined the nitrogen-nutrient requirements of two commercial yeasts
      and three wild strains isolated from inoculated fermentations. The results showed
      that wild strains generally consumed lower amounts of amino acids than commercial
      yeasts. Most amino acids were assimilated during the exponential growth phase;
      only a few - including asparagine and histidine - were metabolized until the end
      of fermentation. The study also sought to determine whether industrial drying
      affected yeast nitrogen requirements.

PMID- 23140685
TI  - Influence of ultra-high pressure homogenisation on antioxidant capacity,
      polyphenol and vitamin content of clear apple juice.
AB  - Ultra-high pressure homogenisation (UHPH) is a recently developed technology and
      is still under study to evaluate its effect on different aspects of its
      application to food products. The aim of this research work was to evaluate the
      effect of UHPH treatments on quality characteristics of apple juice such as
      antioxidant capacity, polyphenol composition, vitamin C and provitamin A
      contents, in comparison with raw (R) and pasteurised (PA) apple juice. Several
      UHPH treatments that include combinations of pressure (100, 200 and 300MPa) and
      inlet temperatures (4 and 20 degrees C) were assayed. Apple juice was pasteurised
      at 90 degrees C for 4min. Antioxidant capacity was analysed using the oxygen
      radical antioxidant capacity (ORAC), 2,2-diphenyl-1-picrylhydrazyl (DPPH), trolox
      equivalent antioxidant capacity (TEAC), ferric reducing antioxidant power (FRAP)
      assay while total phenolic content was determined by the Folin-Ciocalteau assay.
      According to the FRAP and DPPH assays, UHPH processing did not change apple juice
      antioxidant capacity. However, significant differences were detected between
      samples analysed by TEAC and ORAC assays. In spite of these differences, high
      correlation values were found between the four antioxidant capacity assays, and
      also with total polyphenol content. The analysis and quantification of individual
      phenols by HPLC/DAD analytical technique reflects that UHPH-treatment prevented
      degradation of these compounds. Vitamin C concentrations did not change in UHPH
      treated samples, retaining the same value as in raw juice. However, significant
      losses were observed for provitamin A content, but lower than in PA samples. UHPH
      treatments at 300MPa can be an alternative to thermal treatment in order to
      preserve apple juice quality.

PMID- 23140686
TI  - In vitro retardation of glucose diffusion with gum extracted from malva nut seeds
      produced in Thailand.
AB  - Mucilage of malva nut fruit has been used as traditional medicine in Thailand.
      Our laboratory has succeeded in extracting malva nut gum (MNG) from malva nut
      seeds by using alkaline-extraction method. The extract had higher gelling
      properties compared to water-extracted MNG. This research was aimed to
      investigate the effect of MNG on the retardation of glucose diffusion in in vitro
      dialysis processes. The results showed that alkaline-extracted MNG significantly
      (p<0.05) reduced glucose content in dialysate compared to control containing no
      dietary fibre. MNG at 1% (w/w) concentration was more effective than that of 0.5%
      (w/w) concentration. The mixture of MNG and guar gum significantly (p<0.05)
      reduced glucose in dialysate by 50-82% compared to that of control. In starch
      digestion process, the mixture of MNG and guar gum showed greater reduction of
      glucose (3-7 folds) in dialysate at 15-30min.

PMID- 23140687
TI  - Effect of gamma-ray irradiation on the fatty acid profile of irradiated beef
      meat.
AB  - The effect of gamma-ray irradiation on the fatty acid profile of beef meat was
      examined at doses of 2.5, 5.0, 7.5, 10.0 and 15.0kGy by means of (1)H NMR
      spectroscopy. NMR results revealed a clear trend toward an increase in the amount
      of saturated fatty acids and a decrease in the amount of polyunsaturated fatty
      acids in the triacylglycerol composition of the irradiated samples compared to
      the unirradiated sample with increasing the irradiation dose. The observed
      changes in the fatty acid profile were confirmed by gas chromatography analysis
      of the samples irradiated at doses of 7.5, 10.0 and 15.0kGy.

PMID- 23140688
TI  - Actual ratios of triacylglycerol positional isomers consisting of saturated and
      highly unsaturated fatty acids in fishes and marine mammals.
AB  - The distribution of fatty acid species at the (sn-1, 3) position or the (sn-2)
      position of triacylglycerol (TAG) in natural fats and oils has already been
      analysed by many researchers and several interesting results have been reported.
      However, most of these reports only focused on the distribution of fatty acids at
      the or positions in TAG, and did not take account of the combination of fatty
      acids in the TAG, i.e., the TAG positional isomers. In this study, the actual
      ratios of TAG positional isomer pairs, consisting of palmitic acid and highly
      unsaturated fatty acid (HUFA) such as DHA or EPA, in fish and marine mammals were
      investigated using a high-performance liquid chromatography/atmospheric pressure
      chemical ionisation-mass spectrometry (HPLC/APCI-MS) system equipped with tandem
      jointed non-endcapped polymeric ODS columns. The results show that for
      combinations of DHA or EPA with two palmitic acids in the TAG of marine mammals,
      binding was almost all at the alpha position. In contrast, binding of DHA or EPA
      was mainly at the beta position in fish. The preferred DHA and EPA positions in
      TAG were the same in the same marine mammal or fish. The binding position
      tendency of HUFA in TAG positional isomers consisting of two HUFAs and one
      palmitic acid was the same as that for combinations of one HUFA and two palmitic
      acids. These results were interpreted as showing that the preferred fatty acid
      species of sn-glycerol-3-phosphate acyltransferase and 1-acyl-sn-glycerol-3
      phosphate acyltransferase in marine mammals are different to those in fish and
      other animals, or that diacylglycerol acyltransferase in marine mammals favours
      1,2-dipalmitoyl-sn-glycerol formed from 1,2-dipalmitoyl-sn-glycerol-3
      phosphatidate if HUFA is the reaction substrate.

PMID- 23140689
TI  - Interactions between yeast autolysates and volatile compounds in wine and model
      solution.
AB  - The addition of a commercial yeast autolysate to a model solution of five typical
      wine aroma compounds (ethyl octanoate, linalool, 2-phenylethanol, beta-ionone and
      octanoic acid) was investigated considering different variables, such as
      temperature, pH and the presence of highly concentrated natural volatile
      substances in wine (e.g. 3-methyl-1-butanol). The interactions of such compounds
      with both yeast walls and released colloids were studied using gas
      chromatography, with liquid-liquid extraction and solid-phase microextraction.
      The results were compared with those obtained by adding the commercial product to
      a white table wine, spiked with the five standard compounds. The data confirmed
      that yeast walls mainly bind less polar molecules: their loss in synthetic medium
      seemed to increase at higher pH values. Temperature and pH affected differently
      the interactions between yeast colloids and volatile compounds in wine and model
      solution: in complex solutions (as the addition of 3-methyl-1-butanol
      demonstrated) the interaction mechanisms could be influenced by competitive or
      other matrix-related effects, which can reduce the binding of single compounds,
      or even enhance their volatility.

PMID- 23140690
TI  - Effect of ripening on protein content and enzymatic activity of Crimson Seedless
      table grape.
AB  - The evolution of  degrees Brix, protein content, polyphenoloxidase activity and
      peroxidase activity during the ripening of Crimson Seedless table grape was
      studied in three consecutive years (2006, 2007 and 2008). The total protein
      content was determined according to Bradford's dye binding method, and
      polyphenoloxidase (PPO) and peroxidase (POD) were extracted using Triton X-114
      and characterised using spectrophotometric methods. The year had a statistically
      significant effect on all the studied parameters and there was an interannual
      correlation in the evolution of protein, PPO, POD and  degrees Brix. All the
      studied parameters were statistically correlated, except POD activity with
      protein content. Weather conditions during the ripening period had a greater
      effect on protein content than PPO and POD activity.

PMID- 23140691
TI  - Proteolytic action of Lactobacillus delbrueckii subsp. bulgaricus CRL 656 reduces
      antigenic response to bovine beta-lactoglobulin.
AB  - The whey protein beta-lactoglobulin (BLG) is highly allergenic. Lactic acid
      bacteria can degrade milk proteins. The capacity of Lactobacillus delbrueckii
      subsp. bulgaricus CRL 656 to hydrolyse the major BLG epitopes (V41-K60; Y102
      R124; L149-I162) and decrease their recognition by IgE of allergic patients was
      evaluated. The intensity of BLG degradation was analysed by Tricine SDS-PAGE and
      RP-HPLC. Peptides released were identified by LC-MS/MS and the hydrolysates were
      tested for their capacity to inhibit IgE binding by ELISA test. L. delbrueckii
      subsp. bulgaricus CRL 656 degraded BLG (35%, 8h). The sequence analysis of the
      released peptides indicated that this strain degraded three main BLG epitopes.
      BLG-positive sera (3-5year old children) were used for testing IgE binding
      inhibition of BLG hydrolysates from the Lactobacillus strain. The hydrolysates
      were less immuno-reactive (32%) than the heated BLG. L. delbrueckii subsp.
      bulgaricus CRL 656 could be used for developing hypoallergenic dairy products.

PMID- 23140692
TI  - Phenolic composition and free radical scavenging activity of different apple
      varieties in relation to the cultivar, tissue type and storage.
AB  - The aim of this research was to evaluate the influence of genotype, tissue type
      and cold storage on the bioactive compounds content and on the antiradical
      activity (AA) of different apple cultivars (Golden cl. B, Fuji cl. Kiku8,
      Braeburn cl. Hillwell). The content of analysed phyto-compounds depended on the
      clone, on the part of fruit, and to a minor extent, on the storage. For EC(50)
      data, the cultivar represented the main source of variation and the interaction
      with the type of tissue, was significant. The AA of apples, measured by means of
      the DPPH test, was highly correlated to the flavan-3-ols content, which
      represents a good predictor of the apple antiradical power. The new Braeburn's
      clone, the Hillwell, had the worst AA related to a minor phyto-chemical content.
      Also, its phenolic content was dramatically reduced after cold storage (flesh: 
      50%; peels: -20%; p<0.05). Obtained results underlined the key role of the
      genotype on the content of the nutraceutical power of apples, which is important
      to improve their quality and consumption benefits, suggesting to the breeders to
      pay more attention to the potential healthy compounds in the development of new
      hybrids.

PMID- 23140693
TI  - Effect of sterilisation on dietary fibre and physicochemical properties of onion
      by-products.
AB  - Food industries are forced to develop productions without secondary residues.
      Therefore, there is a considerable emphasis on the recovery, recycling and
      upgrading of wastes. The possibility has been suggested for the conversion of
      onion waste into food ingredients, but with a stabilisation treatment being
      necessary. The objective of this work was to study the effect of sterilisation on
      fibre fractions, fibre composition and physicochemical properties of onion by
      products to evaluate the use of sterilised onion by-products as a source of
      fibre. Sterilisation produced insoluble dietary fibre decreases and soluble
      dietary fibre increases, improving the soluble:insoluble ratio. Uronic acids of
      insoluble dietary fibre were partly solubilised and losses of cellulose and
      Klason lignin were observed. Physicochemical properties slightly changed with
      sterilisation. Sterilised by-products showed less oil holding capacity, cation
      exchange capacity and swelling capacity than control ones, although their
      physicochemical properties were generally higher than those of cellulose.
      Therefore, sterilisation would be considered a good method to stabilise onion by
      products to use as a potential dietary fibre ingredient.

PMID- 23140694
TI  - Indigenous proteases in the skin of unicorn leatherjacket (Alutherus monoceros)
      and their influence on characteristic and functional properties of gelatin.
AB  - Indigenous proteases in the skin of unicorn leatherjacket (Alutherus monoceros)
      were characterised using autolytic study. Maximised autolysis was found at pH 7
      and 50 degrees C. Autolysis was markedly inhibited by 0.04mM soybean trypsin
      inhibitor (SBTI), suggesting that heat activated serine protease was predominant
      in the skin. The impact of indigenous proteases on the properties of gelatin
      extracted from unicorn leatherjacket skin was investigated. Gelatin was extracted
      from unicorn leatherjacket skin using distilled water at 50 degrees C for 12h in
      the presence and absence of 0.04mM SBTI. In the presence of SBTI, the degradation
      was markedly inhibited, but a lower gelatin extraction yield was obtained
      (P<0.05). Extracted gelatins contained alpha(1) and alpha(2) chains as the
      predominant components with some degradation peptides. FTIR spectra indicated a
      greater loss of molecular order of the triple helix and a higher degradation was
      found in gelatin extracted in the absence of 0.04mM SBTI. The net charge of
      gelatin samples extracted with and without 0.04mM SBTI became zero at pHs of 8.45
      and 7.31, respectively, as determined by zeta-potential titration. Higher gel
      strength (320.68+/-3.02g) was obtained in gelatin extracted with SBTI, compared
      with that of gelatin extracted without SBTI (288.63+/-1.44g). High emulsifying
      activity index but lower emulsifying stability index was observed in the former.
      Therefore, heat-activated serine protease was involved in the degradation of
      gelatin molecules, thereby affecting the yield, proteinaceous components and
      properties of gelatin from unicorn leatherjacket skin.

PMID- 23140695
TI  - Impact of cover crops in vineyard on the aroma compounds of Vitis vinifera L. cv
      Cabernet Sauvignon wine.
AB  - This study compared the influence of different cover crops with clean tillage on
      wine aroma compounds of 5-year-old Cabernet Sauvignon vines. White clover,
      alfalfa, and tall fescue were used in the vineyard and compared with clean
      tillage. Aroma compounds of wine were analysed by solid-phase microextraction gas
      chromatography-mass spectrometry (SPME-GC/MS). Forty-seven volatile compounds
      were identified and quantified. Wines made from grapes grown with various cover
      crops had higher levels of aroma compounds. Ethyl acetate, isoamyl acetate, ethyl
      octanoate, ethyl hexanoate, phenylethyl acetate, isoamyl alcohol, linalool,
      citronellol, beta-damascenone, alpha-ionone, and 5-amyl-dihydro-2(3H)-furan were
      the impact odorants of sample wines. Wines from cover crop also had higher
      contents of these impact odorants than the control. For different cover crops,
      alfalfa sward yielded the highest levels, followed by the tall fescue treatment.
      According to the data analysis of aroma compounds and sensory assess, permanent
      cover crop may have the potential to improve wine quality.

PMID- 23140696
TI  - The role of polyphenol oxidase and peroxidase in the browning of water caltrop
      pericarp during heat treatment.
AB  - The mechanism of browning involving enzymatic browning was investigated in the
      pericarp of water caltrop, an Asian vegetable popular for its taste and medicinal
      properties. Polyphenol oxidase (PPO) and peroxidase (POD) activities were
      determined in pericarp at various times and temperatures. Water caltrop consisted
      of 44.22% moisture content, 37.23% crude fibre, and 2.63% crude protein. PPO and
      POD activities dropped from 62 and 38units/g sample, respectively, as water
      temperature was increased from 30 to 80 degrees C. Optimum pH and temperature for
      PPO activity was at pH 5.0, 25-45 degrees C, and POD activity peaked at 60
      degrees C. High PPO and POD activities at 40-50 degrees C resulted in degradation
      of phenolic compounds, which led to increased aggregation of browning pigments
      and discolouration (lower L-values) of the pericarp. Enzymatic browning was
      determined as the major factor in the browning discolouration of heat-treated
      water caltrop pericarp.

PMID- 23140697
TI  - Techniques for improving or replacing ageing on lees of oak aged red wines: The
      effects on polysaccharides and the phenolic composition.
AB  - Alternative techniques to the ageing on lees are being looked for in order to
      guarantee the improvements provided by this technique but eliminating its
      disadvantages. The aim of this work was to study the effect of ageing on lees and
      other alternative techniques (addition of beta-glucanase enzymes to the lees; use
      of different yeast commercial preparations with or without beta-glucanase
      enzymes; use of non-toasted oak chips; and ageing on lees together with micro
      oxygenation) on the phenolic compounds, colour, proteins, polysaccharides and
      sensorial characteristics of red wines during vinification and ageing in oak
      barrels for 6months on two consecutive vintages. Only the use of lees together
      with micro-oxygenation seemed to have a positive effect on the colour stability,
      due to the formation of new pigments that allows the intensity and blue notes of
      wines to be maintained during the barrel ageing process. All the techniques
      studied released total and neutral polysaccharides, although the type and content
      of these compounds depended on the technique used, and the yeast derivative
      added. No clear effect was observed with the use of beta-glucanase enzymes. The
      sensory analysis showed that some of the wines treated were better valued than
      the control wines. The results obtained indicated that is difficult to select the
      technique that allows us to obtain the best quality wine.

PMID- 23140698
TI  - Effect of non-starch polysaccharides on the in vitro digestibility and
      rheological properties of rice starch gel.
AB  - The starch digestibility and rheological properties of gels were evaluated in the
      presence of three non-starch polysaccharides (agar, xanthan gum and konjac
      glucomannan) with rice starch. Each polysaccharide was added to 30% (w/w) rice
      starch suspension at defined concentrations and starch gels were prepared. The
      extent of starch gel digestibility was determined by an in vitro method and
      rheological properties by a dynamic oscillatory test and a compression test. The
      added polysaccharides suppressed starch hydrolysis in the gels compared with the
      control, and a concentration dependency of this suppressive effect was observed.
      Adding agar and xanthan gum increased the storage shear modulus (G') of starch
      gels, while adding konjac glucomannan decreased G' values. The results indicate
      that the suppressive effect of non-starch polysaccharides on starch digestibility
      appears to be not only due to the rigidity of the gel, but also the interaction
      between starch and non-starch polysaccharides.

PMID- 23140699
TI  - Evaluation of different Saccharomyces cerevisiae strains on the profile of
      volatile compounds and polyphenols in cherry wines.
AB  - Tart cherries of 'Early Richmond', widely grown in Shandong (China), were
      fermented with six different Saccharomyces cerevisiae strains (BM4*4, RA17,
      RC212, D254, D21 and GRE) to elucidate their influence on the production of
      volatiles and polyphenols. Acetic acid and 3-methylbutanol were found in the
      highest concentrations among all identified volatiles with all six yeast strains,
      followed by 2-methylpropanol and ethyl lactate. RA17 and GRE cherry wines were
      characterised by a higher amount of esters and acids. D254 wine contained a
      higher concentration of alcohols. With respect to polyphenols, five phenolic
      acids and four anthocyanins were identified among all tested samples, with
      chlorogenic and neochlorogenic acids, cyanidin 3-glucosylrutinoside and cyanidin
      3-rutinoside being the major compounds. When using principal component analysis
      to classify the cherry wines according to the volatiles and polyphenols, they
      were divided into three groups: (1) RA17 and GRE, (2) RC212 and D254 and (3)
      BM4*4 and D21.

PMID- 23140700
TI  - Antioxidant capacity, total phenolics, glucosinolates and colour parameters of
      rapeseed cultivars.
AB  - The antioxidant capacity of twenty nine rapeseed varieties was determined by
      using ferric reducing antioxidant power (FRAP) and 2,2'-diphenyl-1-picrylhydrazyl
      (DPPH) methods. Mean FRAP (3190-6326MUmol Trolox/100g) and DPPH (3194-6346MUmol
      Trolox/100g) values for methanolic extracts of rapeseed cultivars did not differ
      significantly. Moreover, the total content of phenolics (756-1324mg sinapic
      acid/100g), glucosinolates (4.2-87.5MUmol/g, respectively), erucic acid (0.0
      56.1%) and colour parameters of the studied rapeseed cultivars were analysed.
      Antioxidant capacity determined by FRAP and DPPH methods correlated significantly
      with total phenolic content (TPC) in rapeseed cultivars (r=0.9332, 0.9339,
      p<0.001). Also, significant, inverse correlations were found between antioxidant
      capacity, total phenolics and luminosity (L(*)) or red colour intensity (a(*)) of
      rapeseed cultivars. Principal component analysis (PCA) allowed the rapeseed
      varieties to be differentiated based on their antioxidant capacities, total
      amounts of phenolics, glucosinolates, erucic acid and colour parameters.

PMID- 23140702
TI  - Encapsulation of ethylene gas into alpha-cyclodextrin and characterisation of the
      inclusion complexes.
AB  - Molecular encapsulation of various apolar compounds with alpha-cyclodextrin
      (alpha-CD) is becoming a widely applied technique to produce food, pharmaceutical
      and agricultural materials. Encapsulated ethylene in the form of inclusion
      complexes (ICs) with cyclodextrin, which is in powder form, could be used in
      fruit ripening and other aspect of plant growth regulation. In this research,
      ethylene was complexed with an alpha-CD under 0.2-1.5MPa for 12-120h. Ethylene
      concentration in the inclusion complexes (ICs) varied from 0.98 to 1.03mol
      ethylene/mole CD. Pressure and time did not increase ethylene concentrations in
      the complexes, but did yield significantly higher amounts of the crystal complex.
      The physico-chemical properties of the ethylene-alpha-CD complexes at various
      concentration of ethylene were characterised using X-ray diffractometry (XRD),
      nuclear magnetic resonance spectroscopy (CP-MAS (13)C NMR), differential scanning
      calorimetry (DSC), thermogravimetry analysis (TGA), scanning electron microscopy
      (SEM) and Fourier transform infrared spectroscopy (FTIR). Complex formation was
      confirmed by sharp peaks in the XRD diffractograms, crystal images by SEM, double
      bond of ethylene gas and chemical shifts at C(4), C(3) and C(5) in NMR spectra,
      intensity changes of C-H bending and CC stretching in the FTIR spectra, and water
      loss and physico-chemical property modifications in the DSC and TGA scans.

PMID- 23140701
TI  - Evaluation of the antioxidant activity of five endemic Ligustrum species leaves
      from Taiwan flora in vitro.
AB  - Leaves from the plant species belonging to the genus Ligustrum are widely used as
      tea or herbal medicine in Europe, China, and Japan. The antioxidant properties of
      five Ligustrum species from Taiwan were compared using in vitro antioxidant
      methods such as DPPH radical scavenging, TEAC, and FRAP assays. Cell-based
      antioxidant methods were used, including Fe(2+)/ascorbate-induced lipid
      peroxidation on brain homogenate and AAPH-induced erythrocyte haemolysis. The
      amounts of major phenolic compounds from the Ligustrum species, including
      phenylpropanoids, flavonoids, and iridoids, were determined by spectrophotometric
      methods. The results showed that all Ligustrum species exhibited antioxidant,
      radical-scavenging, anti-haemolytic, and lipid peroxidation-inhibiting activities
      at different magnitudes of potency. A significant correlation was found between
      antioxidant activity and the amount of antioxidant components, in particular,
      total phenolics and phenylpropanoids. Among all Ligustrum species from Taiwan,
      Ligustrum morrisonense is presented as potential source of natural antioxidants.

PMID- 23140703
TI  - Phenylethanoid glycosides as major antioxidants in Lippia multiflora herbal
      infusion and their stability during steam pasteurisation of plant material.
AB  - Lippia multiflora, a perennial, aromatic shrub commonly known as bush tea has
      recently been identified as an African plant with high commercial potential due
      to its medicinal properties. The plant material was subjected to steam
      pasteurisation to improve its microbial quality. The major compounds of L.
      multiflora herbal infusion, i.e. the phenylethanoid glycosides (PhGs),
      verbascoside, isoverbascoside, nuomioside A and isonuomioside A, and the flavone,
      luteolin-7-O-glucuronide were quantified by HPLC. Verbascoside was the most
      abundant PhG. The PhGs are of interest due to their pharmacological properties.
      Liquid chromatography tandem-mass spectrometry (LC-MS(2)) was used to tentatively
      identify the compounds. The on-line DPPH() (2,2'-diphenyl-1-picrylhydrazyl
      radical) scavenging assay (reaction time=0.45s) applied to the infusion in
      "quantitative" mode, showed the relative order of activity: isonuomioside
      A>isoverbascoside>verbascoside>nuomioside A. In the microplate assay (reaction
      time=2h), isoverbascoside and verbascoside had similar activity. Both compounds
      were less active in the latter assay than the well-known flavan-3-ol antioxidant,
      (-)-epigallocatechin gallate, but more active than caffeic acid and an ester,
      rosmarinic acid. Steam pasteurisation of L. multiflora leaves at maximum exposure
      (150s at ca 99 degrees C) for improved microbial quality did not decrease the
      soluble solids content, phenolic content and antioxidant activities of the
      infusion compared to the untreated control (p<0.05). The PhG content of the water
      soluble solids was as high as 15%, underscoring the potential of L. multiflora
      extract as functional ingredient.

PMID- 23140704
TI  - Stability and anti-glycation properties of intermediate moisture apple products
      fortified with green tea.
AB  - Intermediate moisture products made from blanched apple flesh and green tea
      extract (about 6mg of monomeric flavan 3-ols added per g of dry apple) or
      blanched apple flesh (control) were produced, and their quality attributes were
      investigated over storage for two months at water activity (a(w)) levels of 0.55
      and 0.75, at 30 degrees C. Products were evaluated for colour (L(*), a(*), and
      b(*) Hunter's parameters), phytochemical contents (flavan 3-ols, chlorogenic
      acid, dihydrochalcones, ascorbic acid and total polyphenols), ferric reducing
      antioxidant potential, 2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazyl radical
      scavenging activity and ability to inhibit formation of fructose-induced advanced
      glycation end-products. During storage of the fortified and unfortified
      intermediate moisture apples, water availability was sufficient to support
      various chemical reactions involving phytochemicals, which degraded at different
      rates: ascorbic acid>flavan 3-ols>dihydrochalcones and chlorogenic acid. Colour
      variations occurred at slightly slower rates after green tea addition. In the
      intermediate moisture apple, antioxidant and anti-glycoxidative properties
      decreased at similar rates (half-life was about 80d at a(w) of 0.75, 30 degrees
      C). In the green tea-fortified intermediate moisture apple, the antioxidant
      activity decreased at a slow rate (half-life was 165d at a(w) of 0.75, 30 degrees
      C) and the anti-glycoxidative properties did not change, indicating that flavan 3
      ol degradation involved the formation of derivatives that retained the properties
      of their parent compounds. Since these properties are linked to oxidative- and
      advanced glycation end-product-related diseases, these results suggest that green
      tea fortification of intermediate moisture apple products could be a valuable
      means of product innovation, to address consumers' nutritional needs.

PMID- 23140705
TI  - Effects of pressure on the glucose-ammonium sulphite caramel solutions.
AB  - Effects of pressure on glucose-ammonium sulphite solutions were investigated. The
      reactant (i.e. glucose), intermediate products content, and browning intensity of
      advanced stages were tested using an UV-Vis spectrophotometer and a high
      performance liquid chromatograph to gain a better understanding of the influence
      of pressure on the glucose-ammonium model Maillard reaction system. This study
      indicates that pressure could promote the first step of the reaction, i.e.
      condensation reaction between SO(3)(2-)/ammonium and glucose, but inhibit the
      increase of A(294), A(420) and 5-hydroxymethyl-2-furaldehyde content. The
      mechanism of inhibiting the glucose-ammonium model Maillard reaction might be
      that pressure increases dissociative SO(3)(2-) content in solutions and inhibits
      the degradation of the Amadori rearrangement product.

PMID- 23140706
TI  - The influence of organic and conventional crop management, variety and year on
      the yield and flavonoid level in common buckwheat groats.
AB  - Common buckwheat (Fagopyrum esculentum Moench) is a pseudocereal that is
      cultivated for its achenes that possess a high level of flavonoids. Some
      scientific studies have found that the growing conditions can significantly
      affect the flavonoid content in conventional and organic food products. Hence,
      the present study compared conventionally and organically produced common
      buckwheat with respect to the content of selected flavonoids, thousand achenes
      weight and achene yield. Three buckwheat varieties were grown with organic and
      conventional crop management under the same environmental conditions. The
      thousand achenes weight and achene yield were not significantly influenced by way
      of crop management. The level of rutin, epicatechin, catechin, and epicatechin
      gallate in buckwheat groats (hulled achenes) were quantified with high pressure
      liquid chromatography. Only rutin and epicatechin gallate reached significantly
      higher level in organic groats. However, the differences were influenced by
      environmental conditions in the given year and variety.

PMID- 23140707
TI  - Antioxidant constituents from the stems and fruits of Momordica charantia.
AB  - A new cucurbitane-type triterpene glycoside taiwacin A (1), a new 23,24,25,26,27
      pentanorcucurbitane, taiwacin B (2) and a known cucurbitane-type triterpene
      glycoside (3), and a known steroid glycoside (4), were isolated from the stems
      and fruits of Momordica charantia, respectively. The structure of new compound
      was elucidated by spectroscopic methods. These four compounds, 1, 2, 3 and 4
      revealed ABTS radical cation scavenging activity with an IC(50) values of 119.1+/
      4.3, 204.5+/-1.2, 159.7+/-11.0 and 98.1+/-2.4MUM, respectively. Compounds 1 and 3
      displayed an inhibitory effect on xanthine oxidase (XO) activity with IC(50)
      values of 24.1+/-3.4 and 158.3+/-35.6MUM, respectively. Compounds 2-4
      significantly displayed O(2)(-) scavenging activity with an IC(50) values of
      12.5+/-2.2, 16.5+/-0.1 and 27.3+/-1.4MUM, respectively and the relative oxygen
      radical absorbance capacity (ORAC) values of 2 and 3, using ORAC-pyrogallol red
      (PGR) assay, were determined to be 0.88+/-0.02 and 0.55+/-0.09, respectively.
      These findings showed that 1-4 may be used as antioxidants.

PMID- 23140708
TI  - Main nutrients, phenolics, antioxidant activity, DNA damage protective effect and
      microstructure of Sphallerocarpus gracilis root at different harvest time.
AB  - Sphallerocarpus gracilis roots harvested at two different times (T1: 12-10-2009
      and T2: 15-04-2010) were analysed for their main nutrients, phenolics,
      antioxidant activity, DNA damage protective effect and microstructure. Results
      revealed that higher amounts of starch were detected in T1 S. gracilis root,
      whereas higher levels of reducing sugar, protein, amino acids and phenolic
      compounds were determined in T2 S. gracilis root. The antioxidant activity was
      assessed by DPPH, FRAP and TEAC assay and T2 S. gracilis root was found to
      possess higher antioxidant activity. Also, results of the correlation analysis
      indicated that caffeic, p-coumaric and gallic acids contributed substantially to
      the antioxidant property and there was significant correlation between DPPH
      radicals scavenging capacity and FRAP and TEAC. The highest and lowest DNA damage
      protective effects were found of free phenolic extracts from T2 and T1 S.
      gracilis roots, respectively. The microstructure of S. gracilis root varied
      greatly with the harvest time.

PMID- 23140710
TI  - Trace metal concentrations in Mediterranean blue mussel and surface sediments and
      evaluation of the mussels quality and possible risks of high human consumption.
AB  - The concentrations of trace metals (Fe, Zn, Mn, Ni, Cu, Co and Cr) were
      determined for the first time in Mediterranean blue mussels (Mytilus
      galloprovincialis) and surface sediments. The mussel and sediment samples were
      collected from five sites on the Montenegrin coastal area (southeastern Adriatic
      Sea) in the fall of 2005 and 2006. The collected samples were digested with a
      microwave digestion system. The maximum Fe, Zn, Mn, Ni, Cu, Co and Cr mean
      concentrations in the mussel samples were 603.0, 345.0, 85.0, 18.9, 17.2, 9.1 and
      4.2mg/kg of sample dry weight, respectively. The maximum Fe, Mn, Cr, Ni, Zn, Cu
      and Co concentrations in the sediment samples were 40867, 943.0, 382.0, 336.0,
      67.2, 24.8 and 16.9mg/kg of sample dry weight, respectively. A correlation
      between the metal levels found in the mussel soft tissues with those found in
      sediments, for both 2005 and 2006, could be established, except for the levels of
      Zn observed.

PMID- 23140709
TI  - Effect of pectinase treatment on extraction of antioxidant phenols from pomace,
      for the production of puree-enriched cloudy apple juices.
AB  - Effects of pomace maceration on yield, turbidity, cloud stability, composition of
      phenolics, antioxidant activity and colour properties were studied, to evaluate
      the potential applicability of enzyme preparations in puree-enriched cloudy apple
      juice production. The yield of mixed juice and puree from pomace obtained in the
      enzymatic processing of apple ranged from 92.3% to 95.3%, significantly higher
      than the yield from the control without enzymatic pomace treatment (81.8%).
      Higher turbidity was obtained upon pomace treatment with Pectinex XXL and
      Pectinex Ultra SPL enzymes. The total content of phenolic compounds in apple
      pomace was higher than in raw juices (1520mg/kg and 441mg/L, respectively). The
      total polyphenol yields were higher in juices treated with Pectinex AFP L-4,
      Pectinex Yield Mash and Pectinex XXL, as compared to the control treatment.
      During 6months of storage, a significant change was observed in the content of
      polyphenols, especially in procyanidin fractions.

PMID- 23140711
TI  - Acidic ribosomal protein 60S: A new tomato allergen.
AB  - Three tomato allergens (Lyc e 1, Lyc e 2 and Lyc e 3) have been characterised
      until now. Previous studies have demonstrated the existence of other proteins
      with capacity to bind IgE. The objective of this study was to identify new tomato
      allergens by molecular biology techniques. A tomato peel cDNA library was
      screened using a specific pool of sera from sensitised individuals. A clone was
      obtained and its sequence compared to other described allergens. This clone
      contained 34 aminoacids from the C-terminal region of an acidic ribosomal protein
      60S. This protein showed more than 85% of homology with fungal allergens and
      93.8% of homology with the almond allergen Pru du 5. The clone also contains 169
      base pairs without homology with other known genes and could correspond to non
      coding sequences. The IgE detection with a pool of sera was positive which
      confirms that is a new tomato allergen.

PMID- 23140712
TI  - Quality attributes of starfruit (Averrhoa carambola L.) juice treated with
      ultraviolet radiation.
AB  - Starfruit juice were exposed to ultraviolet (UV-C) light for 0, 30 and 60min at
      room temperature (25+/-1 degrees C). On exposure, the titratable acidity
      significantly decreased, while the decrease in  degrees Brix and pH were not
      significant. With regard to colorimetric parameters, L(*) value increased
      significantly with a subsequent decrease in a(*) and b(*) values corresponding to
      UV treatment time. Except for the ascorbic acid, other antioxidants measured (%
      DPPH inhibition, total phenols, flavonols, flavonoids and antioxidant capacity)
      showed enhancement on expsoure to UV (significant at 60min). Microbial studies
      showed reduction in APC, yeasts and mould counts by 2-log cycle on UV treatments.
      These results supports the application of UV as a measure of non-thermal and
      physical food preservation technique for starfruit juice that can be explored
      commercially to benefit both the producers and consumers.

PMID- 23140713
TI  - RETRACTED: VIS/NIR hyper-spectroscopy technique for the measurement of moisture
      and fat contents of breaded-fried chicken nuggets.
AB  - This article has been retracted: please see Elsevier Policy on Article Withdrawal
      (http://www.elsevier.com/locate/withdrawalpolicy). This article has been
      retracted at the request of the Editor-in-Chief. The authors have plagiarized
      significant parts of a thesis published online in 2005: Quality Evaluation of
      Frying Oil and Chicken Nuggets Using Visible/Nearinfrared Hyper-spectral Analysis
      by Samira Kazemi Sangdehi (http://webpages.mcgill.ca/staff/deptshare/FAES/066
      Bioresource/Theses/theses/339SamiraKazemi2005/339SamiraKazemi2005.pdf). One of
      the conditions of submission of a paper for publication is that authors declare
      explicitly that their work is original and has not appeared in a publication
      elsewhere. Re-use of any data should be appropriately cited. As such this article
      represents a severe abuse of the scientific publishing system. The scientific
      community takes a very strong view on this matter and apologies are offered to
      readers of the journal that this was not detected during the submission process.

PMID- 23140714
TI  - Determination of catechins in green tea infusions by reduced flow micellar
      electrokinetic chromatography.
AB  - A sulfated-beta-cyclodextrin (s-beta-CD) modified reduced flow micellar
      electrokinetic chromatography (RF-MEKC) method was developed and validated for
      the determination of catechins in green tea. The optimal electrolyte consisted of
      0.2% triethylamine, 50mmol/L SDS and 0.8% s-beta-CD (pH=2.9), allowing baseline
      separation of five catechins in 4min. The samples and standards were injected at
      0.6psi for 5s under constant voltage of -30kV. Sample preparation simply involved
      extraction of 2g of tea with 200mL water at 95 degrees C under constant stirring
      for 5min. The method demonstrated excellent performance, with limits of detection
      (LOD) and quantification (LOQ) of 0.02-0.1 and 0.1-0.5MUg/mL, respectively, and
      recovery percentages of 94-101%. The method was applied to six samples of
      Brazilian green tea infusions. Epigallocatechin gallate (23.4-112.4MUg/mL) was
      the major component, followed by epigallocatechin (18.4-78.9MUg/mL), epicatechin
      gallate (5.6-29.6MUg/mL), epicatechin (4.6-14.5MUg/mL) and catechin (3.2
      8.2MUg/mL).

PMID- 23140715
TI  - Equations for spectrophotometric determination of relative concentrations of
      myoglobin derivatives in aqueous tuna meat extracts.
AB  - The percentage of metmyoglobin (%metMb) in aqueous meat extracts of bigeye and
      bluefin tuna and beef samples were estimated using previously reported equations
      derived from the absorption spectra of horse Mb. The results demonstrate that in
      an aqueous extract, the difference in %metMb estimated by the different equations
      was negligible for beef samples. Conversely, in an aqueous tuna extract,
      different %metMb values were obtained with the different equations. The
      discrepancy in the tuna sample results might be due to differences in absorption
      spectra for horse and tuna Mb. Therefore, a new set of equations derived from the
      absorption spectra of bigeye tuna Mb, reported by Matsuura and Hashimoto (1955),
      was established. The accuracy of the proposed equations was compared with the
      cyanmetmyoglobin (cyanmetMb) method. The results show that the total Mb
      concentrations estimated by our proposed equations were in good agreement with
      the results obtained by the conventional cyanmetMb method (R(2)=0.984).
      Therefore, the new set of proposed equations is valid for the spectrophotometric
      determination of the relative proportions of Mb derivatives and total Mb
      concentration in aqueous tuna meat extracts.

PMID- 23140716
TI  - Analysis of volatile compounds of Antrodia camphorata in submerged culture using
      headspace solid-phase microextraction.
AB  - In this work a headspace solid-phase microextraction (HS-SPME) coupled with gas
      chromatography-mass spectrometry (GC-MS) and GC-olfactometry (GC-O) was developed
      to evaluate the profile of the volatile compounds that contribute to the aroma of
      Antrodia camphorata in submerged culture. For this purpose, the HS-SPME sampling
      method for the volatile compounds of A. camphorata in submerged culture was
      optimised by a D-optimal design. A HS extraction of the culture broth of A.
      camphorata followed by incubation on a carboxen/polydimethylsiloxane (CAR/PDMS)
      fibre during 31.8min at 54.6 degrees C gave the most effective and accurate
      extraction of the volatile compounds. By the optimised method, a total of 49
      volatile compounds were identified in culture broth of A. camphorata, while a
      total of 55 volatile compounds were identified in the mycelia. A series of C(8)
      aliphatic compounds (mushroom-like odour), several lactones (fruity odour) and l
      linalool (citrus-like odour) were the most potent key odourant in both the
      mycelia and culture broth. This combined technique is fast, simple, sensitive,
      inexpensive and useful to monitor volatile compounds associated to A. camphorata.

PMID- 23140717
TI  - Influence of baking time and matrix effects on the detection of milk allergens in
      cookie model food system by ELISA.
AB  - Milk allergens are common allergens occurring in foods, therefore raising concern
      in allergic consumers. Enzyme-linked immunosorbent assay (ELISA) is, to date, the
      method of choice for the detection of food allergens by the food industry
      although, the performance of ELISA might be compromised when severe food
      processing techniques are applied to allergen-containing foods. In this paper we
      investigated the influence of baking time on the detection of milk allergens by
      using commercial ELISA kits. Baked cookies were chosen as a model food system and
      experiments were set up to study the impact of spiking a matrix food either
      before, or after the baking process. Results revealed clear analytical
      differences between both spiking methods, which stress the importance of choosing
      appropriate spiking methodologies for method validation purposes. Finally, since
      the narrow dynamic range of quantification of ELISA implies that dilution of
      samples is required, the impact of sample dilution on the quantitative results
      was investigated. All parameters investigated were shown to impact milk allergen
      detection by means of ELISA.

PMID- 23140718
TI  - Determination of calcium-binding constants of caseins, phosphoserine, citrate and
      pyrophosphate: A modelling approach using free calcium measurement.
AB  - Dairy products contain large amount of calcium which is bound to caseins and
      different chelating agents like citrate and polyphosphates. The present study
      aimed to determine the calcium-binding capacities of phosphoserine (SerP),
      caseinophosphopeptide (CPP), beta-casein, caseinate, citrate and pyrophosphate in
      the same conditions of temperature, pH and ionic strength. The free calcium
      (Ca(2+)) was measured using a calcium ion-selective electrode and plotted as a
      function of total calcium concentration. The association constants and the number
      of calcium-binding sites were determined by fitting the experimental data to a
      theoretical model. The phosphate groups of caseins were the main binding sites
      with evidence for participation of carboxylate groups. The intrinsic association
      constants determined by the best fit of the data were in the order: pyrophosphate
      (557*10(3)M(-1))>citrate (20*10(3)M(-1))>beta-casein (5*10(3)M(-1))>caseinate,
      CPP and SerP (~10(3)M(-1)). These findings may be of interest for the development
      of calcium-enriched products to overcome calcium deficiency in specific
      populations.

PMID- 23140719
TI  - Cloud point extraction coupled with ultrasonic-assisted back-extraction for the
      determination of organophosphorus pesticides in concentrated fruit juice by gas
      chromatography with flame photometric detection.
AB  - A new method for the determination of nine organophosphorus pesticides (OPPs):
      Dichlorvos, methamidophos, acephate, diazinon, dimethoate, chlorpyrifos,
      parathion-methyl, malathion and parathion-ethyl in concentrated fruit juice was
      developed using the cloud point extraction coupled with ultrasonic-assisted back
      extraction prior to gas chromatography with flame photometric detection (GC-FPD)
      analysis. The parameters and variables that affect the extraction were
      investigated. Under optimum conditions: a solution containing 6% (W/V)
      polyethylene glycol 6000 (PEG 6000) and 20% (W/V) Na(2)SO(4) for the extraction
      of the OPPs. The coacervation phase obtained was back extracted with ethyl
      acetate. The upper ethyl acetate solution was centrifugated simply for further
      cleanup for the sake of automatic injection. A preconcentration factor of 50 was
      obtained for these nine pesticides. Using this method, the limits of detection
      (LOD) and limits of quantification (LOQ) were in the range of 0.5-3.0 and 1.5
      9.0MUgkg(-1) in concentrated fruit juice, respectively; the relative standard
      deviations (RSD) were <9%.

PMID- 23140720
TI  - Volatile compounds of leaves and fruits of Mangifera indica var. coquinho
      (Anacardiaceae) obtained using solid phase microextraction and hydrodistillation.
AB  - Volatile compounds present on fruits and leaves of Mangifera indica var. coquinho
      were investigated by headspace solid phase microextraction (HS-SPME) and
      hydrodistillation (HD). Conventional techniques, such as hydrodistillation, may
      impart chemical changes to the original oil composition being also time
      consuming. On the other hand, HS-SPME provides solvent-less extractions, shorter
      extraction times and may supply complementary information about the composition
      of the compounds. The HS-SPME technique was previously evaluated by the
      comparative study among the fibres: commercial PDMS, NiTi-ZrO(2) and NiTi-ZrO(2)
      PDMS. The fibre NiTi-ZrO(2)-PDMS showed better sensitivity and precision and was
      used on the extraction of components. The influence of several parameters like
      the time and temperature of extraction and desorption time were examined to
      obtain better efficiency. Fruits and leaves were analysed in mature and immature
      stages. The profiles corresponding to the volatile compounds detected by both
      techniques are discussed.

PMID- 23140721
TI  - Sensitive electrochemical determination of luteolin in peanut hulls using multi
      walled carbon nanotubes modified electrode.
AB  - A simple and highly sensitive electrochemical method was developed for the
      determination of trace-level luteolin, based on the multi-walled carbon nanotubes
      (MWNTs) modified glassy carbon electrode (GCE). The electrochemical behaviours of
      luteolin indicate that MWNTs modified glassy carbon electrode (MWNTs/GCE) can
      greatly enhance the electrocatalytic activity towards the redox of luteolin. It
      leads to a considerable improvement of the redox peak current for luteolin and
      allows the development of a highly sensitive voltammetric sensor for the
      determination of luteolin. A series of experimental parameters including the pH
      of supporting electrolyte, accumulation potential and time were optimised. The
      results showed that the oxidative peak currents increased linearly with the
      concentration of luteolin in the range of 2.0*10(-10) to 3.0*10(-9)M, with a
      detection limit of 6.0*10(-11)M (S/N=3). The analytical performance of this
      sensor has been evaluated for detection of luteolin in peanut hulls as a real
      sample.

PMID- 23140722
TI  - Electrooxidation of flavonoids at platinum electrode studied by cyclic
      voltammetry.
AB  - Flavonoids are natural vegetable dyes synthesized from phenylalanine. They are
      responsible for colour of blooming plant portions. Moreover, they are very
      important for human health due to their activity as free radical acceptors.
      Cyclic and differential pulse voltammetry was used in the determination of
      kinetic parameters of flavonoids electrooxidation. Electrochemical measurements
      of the oxidation of organic compounds can be helpful in understanding how these
      compounds are metabolised by living organisms. Flavonoids electrochemical
      oxidation is an irreversible reaction at a platinum electrode. In the case of
      morin hydrate, rutin, dihydroxyflavone, trihydroxyflavone, hesperidin, quercetin,
      the first step of the electrooxidation includes an exchange of two electrons
      during the oxidation of hydroxyl groups in the ring B. Hydroxyl groups in the
      rings A and C are probably oxidised in subsequent steps. The heterogeneous rate
      constants (k(bh)) determined for the flavonoids electrooxidation are as follows:
      morin - 3.59*10(-4), rutin - 4.42*10(-4), dihydroxyflavone - 4.54*10(-4),
      trihydroxyflavone - 4.19*10(-4), hesperidin - 4.50*10(-4) and quercetin -
      4.63*10(-4)cms(-1). Their anodic transition coefficient ranged from 0.63 to 0.48
      (n=2). Xanthone and flavone were oxidised easiest and quickest among other
      substrates at the platinum electrode with the heterogeneous rate constants
      (k(bh)) of 7.08*10(-4) and 6.46*10(-4)cms(-1), respectively.

PMID- 23140723
TI  - Application of molecular modelling and spectroscopic approaches for investigating
      binding of vanillin to human serum albumin.
AB  - In the present study, the interaction of vanillin and human serum albumin (HSA)
      has been characterised by molecular modelling, fluorescence, Fourier transform
      infrared (FT-IR) and circular dichroism (CD) spectroscopic methods. The results
      of molecular modelling suggested that vanillin was located within the binding
      pocket of subdomain IIA of HSA mainly by hydrophobic forces. The quenching of HSA
      fluorescence takes place with a binding constant (K) of 8.8, 7.7, 5.7,
      4.2*10(4)M(-1) at four different temperatures (288, 298, 308, 318K),
      respectively. Meanwhile, the number of binding site (n~1) was also obtained from
      fluorescence titration data. The enthalpy change DeltaH(0) and the entropy change
      DeltaS(0) were calculated to be -20kJmol(-1) and 5.8Jmol(-1)K(-1) according to
      the Van't Hoff equation. Furthermore, the alterations of protein secondary
      structure in the presence of vanillin were explored by FT-IR and CD spectra.

PMID- 23140724
TI  - Determination of water-soluble vitamins using a colorimetric microbial viability
      assay based on the reduction of water-soluble tetrazolium salts.
AB  - A method for the determination of water-soluble vitamins using a colorimetric
      microbial viability assay based on the reduction of the tetrazolium salt {2-(2
      methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium,
      monosodium salt (WST-8)} via 2-methyl-1,4-napthoquinone (NQ) was developed.
      Measurement conditions were optimized for the microbiological determination of
      water-soluble vitamins, such as vitamin B(6), biotin, folic acid, niacin, and
      pantothenic acid, using microorganisms that have a water-soluble vitamin
      requirement. A linear relationship between absorbance and water-soluble vitamin
      concentration was obtained. The proposed method was applied to determine the
      concentration of vitamin B(6) in various foodstuffs. There was good agreement
      between vitamin B(6) concentrations determined after 24h using the WST-8
      colorimetric method and those obtained after 48h using a conventional method. The
      results suggest that the WST-8 colorimetric assay is a useful method for the
      rapid determination of water-soluble vitamins in a 96-well microtiter plate.

PMID- 23140725
TI  - Iron or zinc dialyzability obtained from a modified in vitro digestion procedure
      compare well with iron or zinc absorption from meals.
AB  - The dialyzability method has been considered a convenient option for screening a
      large number of samples for iron bioavailability. A new setup that allows the
      rapid and efficient application of the dialyzability method has been recently
      proposed. To evaluate the new setup for its applicability in predicting iron and
      zinc bioavailability, dialyzable iron or zinc were compared with iron or zinc
      absorption. A series of solutions and meals that have been employed in published
      studies on iron or zinc absorption were prepared as described in the literature
      and digested in vitro using the new setup. Dialyzability was measured and
      correlated with published data on absorption. Iron or zinc dialyzability measured
      with the proposed setup correlated well with iron or zinc absorption. These
      results suggest that the new setup can be employed in the future applications for
      the prediction of iron or zinc bioavailability.

PMID- 23140726
TI  - A rapid liquid chromatography method for determination of glufosinate residue in
      maize after derivatisation.
AB  - A rapid liquid chromatographic method for glufosinate analysis in maize samples
      after derivatisation has been developed. The labelled glufosinate was separated
      on a Kromasil C(18) column (250mm*4.6mm, 5MUm) and UV detection was applied at
      360nm. The optimisation of derivatisation conditions and the influence of
      different ion-pair reagents on the separation were discussed. The method
      linearity correlation coefficient was 0.9998 in concentrations ranging from 0.1
      to 20mgL(-1). The level of quantification was set to 0.02mgkg(-1), and reached
      pesticide EU-MRLs for glufosinate in the maize samples. The proposed method was
      applied to the quantitative determination of glufosinate in samples with
      recoveries of 98.0-100.5% and RSDs of 2.13-4.13%.

PMID- 23140727
TI  - Identification of isomers of resveratrol dimer and their analogues from wine
      grapes by HPLC/MS(n) and HPLC/DAD-UV.
AB  - A facile method based on HPLC/(-)ESI-MS(n) is established for the analysis of
      seven isomers of resveratrol dimers and three of their analogues in Xinjiang wine
      grapes. The structures of these compounds are positively or tentatively
      determined. Among them, three are tentatively identified as new compounds. MS(n)
      experiments on the [M-H](-) ions provide abundant structural information,
      especially regarding the relative abundance of the key product ions, m/z 333 and
      369 (385 in compound 3), which can be utilised to distinguish whether or not the
      compound identified contains the scaffold of the isomer of a resveratrol dimer.
      The relative abundance of key product ions remains unchanged as collision energy
      varies from 0.60 to 0.95V. All the trans-, and cis-isomers could be identified by
      HPLC/DAD-UV spectra. The UV spectra of compounds 2 and 9 tentatively show cis and
      trans- configurations, respectively.

PMID- 23140728
TI  - Visible micro-Raman spectroscopy for determining glucose content in beverage
      industry.
AB  - The potential of Raman spectroscopy with excitation in the visible as a tool for
      quantitative determination of single components in food industry products was
      investigated by focusing the attention on glucose content in commercial sport
      drinks. At this aim, micro-Raman spectra in the 600-1600cm(-1) wavenumber shift
      region of four sport drinks were recorded, showing well defined and separated
      vibrational fingerprints of the various contained sugars (glucose, fructose and
      sucrose). By profiting of the spectral separation of some peculiar peaks, glucose
      content was quantified by using a multivariate statistical analysis based on the
      interval Partial Least Square (iPLS) approach. The iPLS model needed for data
      analysis procedure was built by using glucose aqueous solutions at known sugar
      concentrations as calibration data. This model was then applied to sport drink
      spectra and gave predicted glucose concentrations in good agreement with the
      values obtained by using a biochemical assay. These results represent a
      significant step towards the development of a fast and simple method for the on
      line glucose quantification in products of food and beverage industry.

PMID- 23140729
TI  - Mid infrared and fluorescence spectroscopies coupled with factorial discriminant
      analysis technique to identify sheep milk from different feeding systems.
AB  - Mid infrared spectroscopy (MIR) combined with multivariate data analysis was used
      to discriminate between ewes milk samples according to their feeding systems
      (controls, ewes fed scotch bean and ewes fed soybean). The MIR spectra were
      scanned throughout the first 11weeks of the lactation stage. When factorial
      discriminant analysis (FDA) with leave one-out cross-validation was applied,
      separately, to the three spectral regions in the MIR (i.e. 3000-2800, 1700-1500
      and 1500-900cm(-1)), the classification rate was not satisfactory. Therefore, the
      first principal component (PCs) scores (corresponding to 3, 10 and 10 for,
      respectively, the 3000-2800, 1700-1500 and 1500-900cm(-1)) of the principal
      component analysis (PCA) extracted from each of the data sets were pooled
      (concatenated) into a single matrix and analysed by FDA. Correct classification
      amounting to 71.7% was obtained. Finally, the same procedure was applied to the
      MIR and fluorescence data sets and 98% of milk samples were found to be correctly
      classified. Milk samples belonging to control and soybean groups were 100%
      correctly classified. Regarding milk samples originating from the scotch bean
      group, only 2 out of 33 samples were misclassified. It was concluded that
      concatenation of the data sets collected from the two spectroscopic techniques is
      an efficient tool for authenticating milk samples according to their feeding
      systems, regardless of the lactation stage.

PMID- 23140730
TI  - Real time monitoring of alcoholic fermentation with low-cost amperometric
      biosensors.
AB  - Screen-printed glucose, ethanol and fructose biosensors, coupled with portable
      instrumentation, and their application to monitor micro-alcoholic fermentations
      (micro-ALFs) in red wine is described. For the fabrication of glucose and ethanol
      biosensors, graphite screen-printed sensors modified with Prussian Blue were
      coupled with oxidase enzymes while for the fructose biosensor, a bare screen
      printed sensor was coated with fructose dehydrogenase and phenazine
      methansulphate was used as electrochemical mediator. The working range,
      reproducibility of probe fabrication and biosensor stability were all evaluated.
      After a recovery study, performed analysing fortified must-wine samples, the
      biosensors were employed to monitor micro-ALFs induced by the inoculation of two
      different strains of Saccharomyces cerevisiae. During the red micro-ALFs, samples
      of must-wine were collected and analysed by use of both biosensors and
      spectrophotometric kits. The data obtained demonstrated that a biosensor-based
      system could represent a useful tool to assist winemakers during wine production.

PMID- 23140731
TI  - Discrimination of cinnamon bark and cinnamon twig samples sourced from various
      countries using HPLC-based fingerprint analysis.
AB  - A simple and efficient HPLC method was developed to evaluate the quality of
      traditional herbal medicines made from cinnamon bark (CB) and cinnamon twig (CT).
      Seven major bioactive ingredients in 56 samples (24 CB and 32 CT) collected from
      China, Vietnam, and Indonesia were separated and quantified. The method was
      validated following the International Conference on Harmonisation (ICH)
      guidelines. A fingerprint analysis method to discriminate between CB and CT using
      major component content levels was developed. The discrimination process included
      the use of similarity indices and partial least-squares discriminant analysis
      (PLS-DA). Classification accuracy by the PLS-DA method was about 98%. The pattern
      analysis method was specific and could be readily used for the comprehensive
      evaluation of cinnamon samples. Therefore, an HPLC fingerprint in combination
      with pattern analysis provides a very flexible and reliable method for quality
      assessment of herbal drugs.

PMID- 23140732
TI  - Validation of a quantitative assay for the total content of lipophilic and
      hydrophilic antioxidants in foods.
AB  - One of the main methods used to assess total antioxidant content in foods is the
      Ferric Reducing Ability of Plasma (FRAP) assay. The FRAP assay has previously not
      been extensively validated. In the present study, 39 pure compounds, such as
      different polyphenols, ascorbic acid, tocopherols, tocotrienols and carotenoids
      dissolved in water/methanol, water/2-propanol and 2-propanol, were tested. Our
      results demonstrate that the FRAP assay can quantitate satisfactorily most
      hydrophilic and lipophilic compounds with antioxidant properties. The reaction
      was followed for 60min. The most extensive reaction occurred within the first
      4min for most compounds and foods. The lipophilic tocopherols and tocotrienols
      were easily quantitated and reached endpoint within 4min while carotenoids were
      somewhat more demanding due to low solubility and slower reaction kinetics. We
      conclude that the FRAP assay, with 4min reaction time, is suitable for high
      throughput screening of total antioxidant content of edible items.

PMID- 23140733
TI  - Micelle mediated extraction and simultaneous spectrophotometric determination of
      vanadium(V) and molybdenum(VI) in plant foodstuff samples.
AB  - A micelle-mediated extraction method for preconcentration of trace quantities of
      V(V) and Mo(VI) as a prior step to their simultaneous spectrophotometric
      determination has been developed. Bromopyrogallol red, cetyltrimethylammonium
      bromide (CTAB) (cationic surfactant) and KI were used as chelating, extraction
      and co-extraction agents, respectively. Mean centering (MC) of ratio spectra has
      been used for the simultaneous analysis of these metal ions. The optimal reaction
      and extraction conditions were optimised and the analytical characteristics of
      the method (e.g., limit of detection, linear range, maximum preconcentration and
      improvement factor) were obtained. Linearity was obeyed in the range 3.0
      50.0ngmL(-1) for V(V) and Mo(VI). The detection limit of the method was 0.5 and
      1.0ngmL(-1) for V(V) and Mo(VI), respectively. The method was applied to the
      simultaneous determination of V(V) and Mo(VI) in several plant foodstuff samples
      successfully.

PMID- 23140734
TI  - Alcohol oxidase- and formaldehyde dehydrogenase-based enzymatic methods for
      formaldehyde assay in fish food products.
AB  - For Gadoid fishes, formaldehyde can be generated in tissues in huge amounts
      during endogenous enzymatic degradation of natural osmoprotectant trimethylamine
      N-oxide. This paper describes two enzymatic methods for assay of formaldehyde in
      fish food products using alcohol oxidase (AOX) and formaldehyde dehydrogenase
      (FdDH) isolated from the thermotolerant methylotrophic yeast Hansenula
      polymorpha. AOX-based method exploits an ability of the enzyme to oxidise a
      hydrated form of formaldehyde to formic acid and hydrogen peroxide monitored in
      peroxidase-catalysed colorimetric reaction. In FdDH-based method, a monitored
      coloured formazane is formed from nitrotetrazolium salt during reduction by NADH,
      produced in formaldehyde-dependent reaction. It was demonstrated an applicability
      of both methods for assay of formaldehyde in fish products. The optimal protocols
      for analysis procedures have been elaborated and analytical parameters of both
      enzymatic methods have been established. The both methods were demonstrated that
      some fish products (hake and cod) contain high formaldehyde concentrations (up to
      100mg/kg wet weight).

PMID- 23140735
TI  - Multi-element determination of Cu, Fe, Ni and Zn content in vegetable oils
      samples by high-resolution continuum source atomic absorption spectrometry and
      microemulsion sample preparation.
AB  - The aim of this work was to evaluate the microemulsification as sample
      preparation procedure for determination of Cu, Fe, Ni and Zn in vegetable oils
      samples by High-Resolution Continuum Source Flame Atomic Absorption Spectrometry
      (HR-CS FAAS). Microemulsions were prepared by mixing samples with propan-1-ol and
      aqueous acid solution, which allowed the use of inorganic aqueous standards for
      the calibration. To a sample mass of 0.5g, 100MUL of hydrochloric acid and propan
      1-ol were added and the resulting mixture diluted to a final volume of 10mL. The
      sample was manually shaken resulting in a visually homogeneous system. The main
      lines were selected for all studied metals and the detection limits (3sigma,
      n=10) were 0.12, 0.62, 0.58 and 0.12mgkg(-1) for Cu, Fe, Ni and Zn, respectively.
      The relative standard deviation (RSD) ranged from 5% to 11 % in samples spiked
      with 0.25 and 1.5MUgmL(-1) of each metal, respectively. Recoveries varied from
      89% to 102%. The proposed method was applied to the determination of Cu, Fe, Ni
      and Zn in soybean, olive and sunflower oils.

PMID- 23140736
TI  - Monitoring multi-class pesticide residues in fresh grape by hollow fibre sorptive
      extraction combined with gas chromatography-mass spectrometry.
AB  - A fast and sensitive multi-residue analysis method is reported for simultaneous
      determination of 25 pesticides of chemical classes which are spiked into fresh
      grape. The sample pretreatment method involves extraction and clean-up in one
      step with SiO(2) hollow fibre from 1.0mL fresh grape slurry to minimise the
      matrix effects, and determination by gas chromatography-mass spectrometry with
      selective ion monitoring mode. The validation of the optimised method in terms of
      linearity, precision, recovery and repeatability showed that the proposed
      procedure is sensitive (the limits of detection were in the range of 0.0009
      0.0084MUgmL(-1) for 25 pesticides), precise and repeatable (average recoveries
      were between 61% and 108% with relative standard deviations from 4.0% to 12.4 %).
      The proposed method was also applied to the analysis of these groups of
      pesticides in fresh grape sample purchased from the local markets of Lanzhou
      (China), while no residues of the selected pesticides were detected in the
      sample.

PMID- 23140737
TI  - A new colorimetric method to quantify beta-1,3-1,6-glucans in comparison with
      total beta-1,3-glucans in edible mushrooms.
AB  - Mushroom beta-glucans are known for their activity as biological response
      modifiers and anticarcinogenic agents. beta-1,3-1,6 Branched glucans with a
      triple helix tertiary structure are recognised as the most potent ones. In the
      present work, a colorimetric method for beta-1,3-1,6-glucan quantification based
      on the dye Congo red is introduced. This method is specific for beta-glucans with
      a triple helix. The beta-1,3-1,6-glucan content of mycelia and fruiting bodies
      from various mushrooms was determined and compared with the total beta-1,3-glucan
      content, measured by a fluorimetric method. The results show equal amounts of
      beta-1,3-1,6- and total beta-1,3-glucans in the analysed species but obvious
      differences between mycelia and fruiting bodies. On the average, 3% of mycelia
      and 8% of fruiting body dry mass consist of beta-1,3-1,6-glucans. The average
      percentage of beta-1,3-1,6-glucans in the total beta-1,3-glucan content differs
      between mycelia (46%) and fruiting bodies (87%).

PMID- 23140738
TI  - A rapid quantitative determination of phenolic acids in Brassica oleracea by
      capillary zone electrophoresis.
AB  - A simple and rapid capillary zone electrophoresis method to quantitatively
      determine the phenolic acid contents in brassica vegetables is described.
      Phenolic compounds were extracted from broccoli, broccolini, Brussels sprouts,
      cabbage and cauliflower and the main hydroxycinnamic acids (sinapic, ferulic, p
      coumaric and caffeic acids) were isolated by solid phase extraction with C18
      cartridges. Using an optimised method, the four analytes were separated in less
      than 7min in a 50MUm*60cm capillary with a 15mM borate buffer (pH=9.13) and a
      separation voltage of 30kV at 30 degrees C. A linear relationship was observed
      for the method (r=0.9997-0.9999) with detection limits ranging from 1.1 to
      2.3mg/kg of vegetables for the analytes. This method demonstrated good
      reproducibility with coefficients of variation of less than 5% for peak area and
      less than 1% for migration time (n=7). The method was successfully applied to
      quantitatively determine the phenolic acid contents in a range of brassica
      vegetables and the results were in good agreement when compared to those from
      high performance liquid chromatography analysis.

PMID- 23140739
TI  - A very simple, fast, and non-destructive approach to predict the time at which
      edible oils submitted to high temperature reach the established limits of safety.
AB  - Relationships between the time at which edible oils reach 25% in weight of polar
      compounds and their original composition, expressed as molar percentage of their
      acyl groups, were tested; the aim was to analyze the influence of oil composition
      on its performance at high temperature. Likewise, relationships between the
      composition of the oils and their original percentage in polar compounds were
      explored. It has been shown for the first time that a very close relationship
      between the percentage in weight of polar compounds of the original oils, and the
      time at which they reach 25% of polar compounds exits. This relationship permits
      the prediction, in a very simple, fast and non-destructive way, of the
      performance of edible oils at frying temperature from their original percentage
      in polar compounds, in other words from their original dielectric constant. This
      approach is very useful for food safety, with important technological and
      economic repercussions.

PMID- 23140740
TI  - Identification and quantification of phenolic compounds from pomegranate (Punica
      granatum L.) peel, mesocarp, aril and differently produced juices by HPLC-DAD
      ESI/MS(n).
AB  - Phenolic compounds were extracted from pomegranate (Punica granatum L.) peel,
      mesocarp and arils. Extracts and juices were characterised by HPLC-DAD-ESI/MS(n).
      In total, 48 compounds were detected, among which 9 anthocyanins, 2 gallotannins,
      22 ellagitannins, 2 gallagyl esters, 4 hydroxybenzoic acids, 7 hydroxycinnamic
      acids and 1 dihydroflavonol were identified based on their UV spectra and
      fragmentation patterns in collision-induced dissociation experiments. To the best
      of our knowledge, cyanidin-pentoside-hexoside, valoneic acid bilactone,
      brevifolin carboxylic acid, vanillic acid 4-glucoside and dihydrokaempferol
      hexoside are reported for the first time in pomegranate fruits. Furthermore,
      punicalagin and pedunculagin I were isolated by preparative HPLC and used for
      quantification purposes. The ellagitannins were found to be the predominant
      phenolics in all samples investigated, among them punicalagin ranging from 11 to
      20g per kilogram dry matter of mesocarp and peel as well as 4-565mg/L in the
      juices. The isolated compounds, extracts and juices were also assessed by the
      TEAC, FRAP and Folin-Ciocalteu assays revealing high correlation (R(2)=0.9995) of
      the TEAC and FRAP values, but also with total phenolic contents as determined by
      the Folin-Ciocalteu assay and by HPLC. Selection of raw materials, i.e. co
      extraction of arils and peel, and pressure, respectively, markedly affected the
      profiles and contents of phenolics in the pomegranate juices, underlining the
      necessity to optimise these parameters for obtaining products with well-defined
      functional properties.

PMID- 23140741
TI  - One-year monitoring of aflatoxins and ochratoxin A in tiger-nuts and their
      beverages.
AB  - A sensitive and selective liquid chromatography-triple quadrupole-tandem mass
      spectrometry (LC-ESI-MS-MS) method was developed for the routine analysis of
      aflatoxins (AFB(1), AFB(2), AFG(1) and AFG(2)) and ochratoxin A (OTA) in tiger
      nuts and tiger-nut beverage (horchata). A matrix solid phase dispersion was
      adapted to eliminate lipidic interferences. The solid support was C(18), while
      the elution solvent was acetonitrile. Mean recoveries obtained at two
      fortification levels were 72-83% and 71-81% for horchata and tiger nut
      respectively with relative standard deviations (RSDs) <13% and 15% respectively.
      The LC-MS-MS method allowed quantification and identification at low levels in
      two matrices. The method was applied for the routine analysis of tiger-nuts and
      horchata samples collected from different supermarkets of Valencia (Spain) during
      one year (March 2009-March 2010). A total of 238 samples were analysed and 32
      samples were found positives for OTA, AFB(1), AFB(2) and AFG(2).

PMID- 23140742
TI  - Exploiting second-order advantage using PARAFAC2 for fast HPLC-DAD quantification
      of mixture of aflatoxins in pistachio nuts.
AB  - A new methodology using second-order calibration based on PARAllel FACtor
      analysis 2 (PARAFAC2) is developed for fast quantification of aflatoxins B(1),
      B(2), G(1) and G(2) in pistachio samples by liquid chromatography with diode
      array detection (LC-DAD). Solvent and solid phase extractions were used for
      sample preparation steps. In this work, a gradient elution programme was
      optimised to make co-elutions between analytes and also to shorten the analysis
      time. Prediction was made on synthetic and real validation samples with a mixture
      calibration design. Special circumstances such as overlapping of analytes, the
      lack of spectral selectivity and also the lack of trilinearity, have been
      compensated with "mathematic separation" through PARAFAC2 modelling. The results
      showed an acceptable performance of PARAFAC2 for resolution and quantification of
      all analytes in a single array exploiting the second-order advantage. With the
      proposed method, the chromatographic run time and also the time for data analysis
      were reduced significantly.

PMID- 23140743
TI  - Development of a real-time PCR method for the simultaneous detection of soya and
      lupin mitochondrial DNA as markers for the presence of allergens in processed
      food.
AB  - Lupin and soya are members of the Leguminosae family which are recognised as some
      of the richest source of vegetable proteins. Lupin- and soya-containing products
      are available on the EU market and could cause severe adverse reactions in
      allergic individuals, even if consumed at low concentrations. In this context the
      development of methods for reliable detection of these allergens in food products
      is a useful tool for the surveillance of established legislation on food
      labelling within the EU. This work described the development of a duplex real
      time PCR method allowing the simultaneous detection of traces of lupin and soya
      in processed food based on a specific TaqMan(r) probe designed on a mitochondrial
      tRNA-MET gene. A set of primers and probes was designed for the amplification of
      a 168 and 175bp fragment of lupin and soya mitochondrial DNA, respectively. The
      performance of the method was established using lupin and soya flours and cookies
      baked from lupin- and soya-containing dough (different concentrations and baking
      times). The PCR platform yielded consistent and repeatable results. The
      specificity of the system was tested with DNA from 28 plant species. The
      sensitivity of the method was suitable to detect allergenic ingredients in the
      low mg per kg range. Both lupin and soya at a level of 2.5mg per kg food matrix
      could be detected in cookies baked at 180 degrees C for 10min. The method was
      successfully applied to bakery (e.g. bread) and vegetarian (e.g. non-meat
      sausages) food products that contain or may contain soya and/or lupin as
      ingredient or contaminant (according to the declaration on the product label).

PMID- 23140744
TI  - Determination of melamine by flow injection analysis based on chemiluminescence
      system.
AB  - In this paper, based upon the phenomenon that melamine can obviously enhance the
      CL signal of the luminol-H(2)O(2) system in basic medium, a simple, rapid and
      sensitive flow injection chemiluminescence (FI-CL) method for the determination
      of melamine has been developed. Under the optimum conditions, the linear range
      for the determination of melamine was 0.2-80MUgmL(-1) with a detection limit of
      0.12MUgmL(-1) calculated as proposed by IUPAC and a relative standard deviation
      of 3.26% for 11 solutions of 10MUgmL(-1) melamine on the same day. The proposed
      method was satisfactorily applied to determine melamine in milk-based products
      and satisfactory results were obtained without interferences from the sample
      matrix. Moreover, one assay produce takes only 25s and the minimum sampling rate
      is about 120 samplesh(-1), which indicated that the FI-CL method was suitable for
      high throughput and real-time melamine analysis.

PMID- 23140745
TI  - Analysis of nisin A, nisin Z and their degradation products by LCMS/MS.
AB  - The peptides nisin A and nisin Z belong to type-A lantibiotics applied as
      preservatives in cheese production. The present study optimised and validated a
      liquid chromatography-tandem mass spectrometry (LCMS/MS) method for the analysis
      of nisin A in cheese. Since nisin A was not detectable in nisin-containing
      commercial cheese samples, an additional LCMS/MS method for the quantification of
      nisin Z was developed and validated. Quantification was performed by external
      calibration and standard addition. The latter method provided a non-significantly
      higher recovery rate for the tested cheese matrix. During the production of
      processed cheese, nisin A and nisin Z undergo significant degradation. Six
      degradation products of nisin A or nisin Z, respectively, were detected and
      assigned to nisin A/Z+H(2)O, nisin A/Z(1-32), and nisin A/Z(1-32)+H(2)O. In two
      out of eight commercial processed cheese samples, 1.6, resp. 1.7mg nisin Z/kg
      cheese was measured, whereas nisin A was not detectable in any of the samples.

PMID- 23140746
TI  - Multiresidue method for determination of 88 pesticides in berry fruits using
      solid-phase extraction and gas chromatography-mass spectrometry: Determination of
      88 pesticides in berries using SPE and GC-MS.
AB  - A method using solid phase extraction (SPE) cleanup followed by gas
      chromatography-mass spectrometry (GC-MS) has been established for quantitative
      determination of 88 pesticide residues in berry fruits including raspberry,
      strawberry, blueberry and grape. Based on an appraisal of the characteristics of
      GC-MS, validation experiments were conducted for 88 pesticides. In the method,
      solid-phase extraction was carried out using Envi-Carb cartridge coupled with
      NH(2)-LC cartridge with acetonitrile-toluene (3:1, v/v) as the eluted solvent. In
      the linear range of each pesticide, the correlation coefficient was R(2)?0.99. At
      the low, medium and high three fortification levels of 0.05-0.5mgkg(-1),
      recoveries fell within 63-137%. The relative standard deviation was between 1%
      and 19% for all 88 pesticides. Low limits of detection (0.006-0.05mgkg(-1)) and
      quantification (0.02-0.15mgkg(-1)) were readily achieved with this method for all
      tested pesticides.

PMID- 23140747
TI  - Integrating satellite images and spectroscopy to measuring green and black tea
      quality.
AB  - This study quantifies the effects of green leaf and black tea parameters that
      influence tea quality in Northeast India. It was motivated by a decline in tea
      quality that is of concern to tea growers. The rationale of the study is to
      identify the different parameters that have a significant influence on liquor
      brightness and other variables measuring tea quality. Here, we investigate
      several methods for estimating tea quality based on tea quality data, near
      infrared spectroscopy and remotely sensed data (NDVI). Attention focused on two
      high yielding clones (TV1 and S3A3). NDVI was obtained from ASTER images.
      Statistical analysis shows that liquor brightness is affected by the levels of
      caffeine content, theaflavins and catechins. Relationships exist between quality
      parameters and remote sensing in particular for the S3A3 clone. NDVI has a
      positive relation with caffeine, theogallin, EC, and ECG. NIR is negatively
      related to caffeine, theogallin, and catechins. We conclude that NDVI and Near
      Infrared (NIR) spectroscopy have a large potential to be used for monitoring tea
      quality in the future.

PMID- 23140748
TI  - Microwave-assisted extraction and determination of cyanuric acid residue in
      infant formula samples by liquid chromatography-tandem mass spectrometry.
AB  - In the present work, microwave-assisted extraction method in combining with
      liquid chromatography-tandem mass spectrometry (LC-MS/MS) was proposed for the
      determination of cyanuric acid (CYA) in infant formula samples. The separation
      was performed on a MERCK ZIC HILIC column (150*2.1mm i.d., 5MUm) with gradient
      elution of 20mM ammonium acetate solution - acetonitrile. The method could
      respond linearly with cyanuric acid at concentrations from 1.0 to 50ngmL(-1) with
      a quantification limit of 0.25mgkg(-1). The intra- and inter-day precision was
      less than 4% and the recovery of the assay was in the range of 86.7-93.1%. In the
      analysis of practical spiked infant formula samples, the new method yielded
      satisfactory results. Due to its simplicity and accuracy the straightforward
      method is particularly suitable for routine cyanuric acid detection.

PMID- 23140749
TI  - Simultaneous determination of flavanones, hydroxycinnamic acids and alkaloids in
      citrus fruits by HPLC-DAD-ESI/MS.
AB  - A simple and accurate method has been developed to simultaneously separate and
      determine 10 bioactive compounds in citrus fruits by high-performance liquid
      chromatography coupled with diode array detection and electrospray ionisation
      mass spectrometry (HPLC-DAD-ESI/MS). This HPLC assay was performed on a reversed
      phase C18 column with acetonitrile and 0.1% (v/v) aqueous formic acid as mobile
      phase. DAD has been performed at 273, 283 and 324nm for quantification of the
      alkaloids, flavanones and hydroxycinnamic acids. MS was also employed to identify
      the each analyte. Ten analytes (naringin, hesperidin, neohesperidin, ferulic
      acid, p-coumaric acid, chlorogenic acid, caffeic acid, octopamine, synephrine and
      tyramine) demonstrated good linearity (r?0.9990) in a relatively wide
      concentration range. The method revealed high average recovery (range, 92.1
      97.9%) and good precision with interday and intraday variations with less than
      4.71%. The limits of detection (LODs) ranged from 0.02 to 0.11MUg/ml, while the
      limits of quantification (LOQs) were defined in the range of 0.08-0.39MUg/ml. The
      proposed method has been successfully applied to analyse three types of bioactive
      constituents in eight citrus hybrids pulps and eight citrus hybrids peels, which
      has been successfully cultivated in China.

PMID- 23140750
TI  - A headspace solid-phase microextraction gas-chromatographic mass-spectrometric
      method (HS-SPME-GC/MS) to quantify hexanal in butter during storage as marker of
      lipid oxidation.
AB  - A method using headspace solid-phase microextraction (HS-SPME) combined with gas
      chromatography-mass spectrometry (GC/MS) was developed and validated for the
      extraction and quantification of hexanal content in butter (at ngg(-1) level)
      during storage at 4 degrees C. The variability of hexanal content among seasons
      of production and the influence of high extraction temperature on ex-novo
      formation of hexanal were also evaluated. The HS-SPME conditions were optimised
      and analytical parameters of the method (linearity, accuracy, and precision)
      demonstrate its usefulness. The reproducibility and accuracy of the quantitative
      analysis was assured by the use of D(12)-hexanal as internal standard. For the
      applications, the headspace was extracted using CAR/PDMS fiber for 180min at 4
      degrees C. Hexanal contents in samples during all storage period (shelf-life) and
      from butters produced in different seasons were analysed. Butter samples at the
      end of shelf-life and samples produced in August showed highest values of
      hexanal, confirming that the temperature both in storage and distribution phases
      represents a critical factor to maintain the quality of butter.

PMID- 23140751
TI  - Determination of Gibberellin A3 residue in fruit samples by liquid chromatography
      tandem mass spectrometry.
AB  - A fast, simple, low cost, and high throughput method has been developed for the
      determination of Gibberellin A3 residue in fruit samples (apple, orange, peach,
      pear and grape). Analysis is performed by LC-MS/MS operated in the multiple
      reaction monitoring (MRM) mode, acquiring two specific precursor-product ion
      transitions per target compound. The method has been validated showing good
      linearity and selectivity. Limits of quantification (LOQs) were 10MUgkg(-1) for
      apple, orange, peach, pear and grape samples. The average recoveries, measured at
      three concentration levels (10, 20 and 200MUgkg(-1)) were in the range 77.8-96.2%
      for the compound tested with relative standard deviations below 13.7%. The
      proposed method is rapid, simple and could be utilised for the routine analysis
      of Gibberellin A3 in fruit samples.

PMID- 23140752
TI  - Optimizing cervical cancer prevention strategies in the United States.

PMID- 23140753
TI  - Editorial: randomized clinical trials in inflammatory bowel disease.

PMID- 23140754
TI  - Enantioselective synthesis of optically active 3,3-diarylpropanoates by conjugate
      hydrosilylation with chiral Rh-bis(oxazolinyl)phenyl catalysts.
AB  - Conjugate hydrosilylation of 3,3-diarylacrylate derivatives catalyzed by chiral
      rhodium-bis(oxazolinyl)phenyl complexes (1 mol %) at 60  degrees C for 2 h was
      investigated to prepare optically active 3,3-diarylpropanoate derivatives in high
      yields up to 99% yield and high enantioselectivities up to 99%.

PMID- 23140755
TI  - Clinical significance of a single isolation of pathogenic nontuberculous
      mycobacteria from sputum specimens.
AB  - A single sputum culture positive for nontuberculous mycobacteria (NTM) could be
      an early sign of NTM lung disease. We found that 14% of patients with a single
      sputum culture positive for pathogenic NTM were diagnosed with NTM lung disease
      during the median follow-up period of 16 months.

PMID- 23140756
TI  - Comparison of respiratory mechanics in adult patients undergoing minimally
      invasive repair of the pectus excavatum and removal of a pectus bar.
AB  - OBJECTIVE: The objective of this study was to compare the respiratory mechanics
      and gas exchange in adult patients undergoing minimally invasive repair of the
      pectus excavatum (MIRPE group) and removal of a pectus bar (bar removal group).
      DESIGN: A prospective observational study. SETTING: A tertiary university
      hospital. PARTICIPANTS: Thirty-two patients scheduled for elective MIRPE or
      removal of a pectus bar. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      Spirometry was used to measure the peak inspiratory airway pressure (PIP), static
      compliance, and respiratory resistance. The measurements were recorded at 1
      minute after beginning mechanical ventilation (T0), 15 minutes after beginning
      sevoflurane inhalation (T1), and after the insertion (or removal) of a pectus bar
      through the chest wall (T2). Pulmonary gas exchange was assessed by calculating
      the alveolar arterial oxygen tension difference (AaDO2) before surgical incision
      and after insertion (or removal) of the pectus bar. In the MIRPE group, static
      compliance was decreased significantly (p < 0.001), and PIP was increased
      significantly (p < 0.001) after insertion of the pectus bar (T2) compared with
      baseline. In contrast, the bar removal group showed the opposite results. There
      were significant differences in static compliance and PIP at T2 between the
      groups (p = 0.002 and 0.026, respectively). AaDO2 was increased significantly in
      the MIRPE group compared with the bar removal group (p = 0.012). CONCLUSIONS:
      Insertion of the pectus bar through the chest wall results in significant changes
      in respiratory mechanics and gas exchange. Therefore, close attention to
      pulmonary function is required during and after these surgical procedures.

PMID- 23140757
TI  - [Utility of capsule endoscopy with flexible spectral imaging color enhancement in
      the diagnosis of small bowel lesions].
AB  - INTRODUCTION: Capsule endoscopy (CE) is the technique of choice to detect small
      bowel lesions. Flexible spectral imaging color enhancement (FICE) software has
      recently been incorporated into the new RAPID 6.0 workstation, which allows three
      distinct patterns to be visualized in the mucosal structure according to
      different wavelengths. The aim of this study was to evaluate whether CE-FICE is
      more effective in detecting lesions than standard visualization. PATIENTS AND
      METHODS: Fifty lesions were detected by CE in 41 consecutive patients in 2010.
      These patients were administered PillCamTM SB2 in our center and were classified
      into three groups: 1) vascular lesions and angiodysplasias (18 lesions), 2)
      erosions and ulcers (18 lesions) and 3) polyps and tumors (14 lesions).
      Subsequently, these lesions were independently analyzed with the available FICE
      patterns by three endoscopists, who assigned them a score according to the
      changes in the visualization of each FICE mode: +2, strong improvement; +1,
      slight improvement; 0, no relevant changes; -1, slight worsening; -2, clear
      worsening. When the sum of the scores of the three observers was 3 or more,
      visualization was considered to have improved; a score of 2 to -2 indicated no
      change; and a score of from -3 to -6 indicated poorer visualization. RESULTS: The
      FICE 1 mode improved visualization of angiodysplastic and vascular lesions in
      16/18 patients (88.9%) and that of erosions/ulcers in 14/18 patients (77.8%). The
      FICE 2 mode improved these lesions in 88.9% and 55.5%, respectively. The FICE 3
      mode only improved visualization of these lesions in 5/18 (27.7%) and 1/18
      patients (5.5%), respectively. Likewise, the distinct FICE modes improved
      visualization of polyps/tumors in 2/14 (14.2%), 3/13 (21.4%) and 4/14 (28.5%) for
      FICE 1, 2 and 3, respectively. CONCLUSIONS: The application of CE-FICE modes 1
      and 2 could improve the characterization of angiodysplastic/vascular lesions and
      erosions or ulcers in small bowel lesions. However, FICE 3 seems to provide no
      significant advantages. None of the CE-FICE modes seems to improve the
      characterization of polyps and tumors.

PMID- 23140758
TI  - A review investigating the effect of allopurinol on the progression of kidney
      disease in hyperuricemic patients with chronic kidney disease.
AB  - This communication provides a brief report on the studies evaluating the use of
      allopurinol for delay of kidney disease progression and a discussion of the
      current limitations and future research needed. To date, only 5 studies have
      reported a delay in the progression of kidney disease with allopurinol use; a
      sixth study is currently underway. Allopurinol does seem to delay the progression
      of kidney disease as measured by using serum creatinine and glomerular filtration
      rates in hyperuricemic patients with chronic kidney disease. However, randomized,
      double-blind, placebo-controlled trials enrolling more patients and controlling
      for confounding variables are needed to confirm these findings.

PMID- 23140760
TI  - Taking the starch out of hereditary colorectal cancer.

PMID- 23140759
TI  - Health-related quality of life in children with sickle cell disease using the
      child health questionnaire.
AB  - INTRODUCTION: This study sought to determine if changes in parent-reported health
      related quality of life (HRQOL) in children with sickle cell disease (SCD-SS)
      occurred after participation in a nutritional supplementation study and to
      compare HRQOL responses with normative scores from non-White children. METHOD:
      Parents of children with SCD-SS between the ages of 5 and 13 years completed the
      Child Health Questionnaire (CHQ-PF50) at baseline and at 12 months. RESULTS: For
      the 47 children (8.6 +/- 2.4 yrs, 43% female), baseline Child Health
      Questionnaire scale scores were significantly lower than normative scale scores
      for parental emotional impact, general health, and overall physical health, but
      they were higher for mental health. After the nutritional supplementation study,
      overall physical health and parental emotional impact improved to normative
      levels. Furthermore, physical role functioning significantly improved.
      DISCUSSION: Participation in a nutritional study had a positive impact on parent
      reported HRQOL physical scores in children with SCD-SS. More research is
      necessary to develop care providers' awareness and adequate HRQOL interventions
      for this population.

PMID- 23140763
TI  - Evidence-based medicine?!... What for?

PMID- 23140764
TI  - KMUP-1 inhibits hypertension-induced left ventricular hypertrophy through
      regulation of nitric oxide synthases, ERK1/2, and calcineurin.
AB  - Hypertension can induce left ventricular hypertrophy (LVH), and the nitric oxide
      (NO) pathway plays an important role in the pathogenesis of cardiac hypertrophy.
      This study aimed to examine whether KMUP-1, a novel xanthine-based derivative,
      could inhibit LVH in spontaneously hypertensive rats (SHRs) and to investigate
      potential mechanisms underlying its antihypertrophic effects. Two groups of
      animals with chronic or subacute LVH were treated. In the chronic LVH group, KMUP
      1 (10 or 30 mg/kg/d orally) was administered for 28 days to both normotensive
      rats and SHRs. In the subacute LVH group, KMUP-1 (0.5 mg/kg/d intraperitoneally)
      or sildenafil (0.7 mg/kg/d intraperitoneally) was administered for 10 days with
      or without co-treatment with the nitric oxide synthase (NOS) inhibitor N-omega
      nitro-l-arginine (L-NNA; 20 mg/L orally). After treatment, the effects of KMUP-1
      or sildenafil on hypertension, cardiac hypertrophy, survival, expression of the
      NO/soluble guanylate cyclase (sGC)/protein kinase G (NO/sGC/PKG) pathway in the
      aorta andleft ventricle, and calcineurin A/extracellular signal-regulated kinase
      1/2 (ERK1/2) signaling in the left ventricle were examined. In the chronic LVH
      group, the SHRs developed hypertension with LVH over the 28 days. KMUP-1
      attenuated the hypertension and LVH, increased survival rate, enhanced
      endothelial NOS/cyclic guanosine monophosphate/PKG (eNOS/cGMP/PKG) and decreased
      inducible NOS (iNOS) expression in the aorta and left ventricle of the SHRs. In
      the subacute LVH group, both KMUP-1 and sildenafil administered for 10 days
      attenuated the LVH in SHRs, with enhanced eNOS/cGMP/PKG and suppressed
      iNOS/calcineurin A/ERK1/2 expression in the left ventricle. In addition, both
      KMUP-1 and sildenafil attenuated L-NNA-induced LVH. KMUP-1 inhibition of
      hypertension-induced LVH with associated upregulation of eNOS, downregulation of
      iNOS in both the aorta and left ventricle, and attenuation of calcineurin A and
      ERK1/2 signaling in the left ventricle.

PMID- 23140766
TI  - Loading effects of anterior cervical spine fusion on adjacent segments.
AB  - Adjacent segment degeneration typically follows anterior cervical spine fusion.
      However, the primary cause of adjacent segment degeneration remains unknown.
      Therefore, in order to identify the loading effects that cause adjacent segment
      degeneration, this study examined the loading effects to superior segments
      adjacent to fused bone following anterior cervical spine fusion. The C3-C6
      cervical spine segments of 12 sheep were examined. Specimens were divided into
      the following groups: intact spine (group 1); and C5-C6 segments that were fused
      via cage-instrumented plate fixation (group 2). Specimens were cycled between 20
      degrees  flexion and 15 degrees  extension with a displacement control of 1
      degrees /second. The tested parameters included the range of motion (ROM) of each
      segment, torque and strain on both the body and inferior articular process at the
      superior segments (C3-C4) adjacent to the fused bone, and the position of the
      neutral axis of stress at under 20 degrees  flexion and 15 degrees  extension.
      Under flexion and Group 2, torque, ROM, and strain on both the bodies and facets
      of superior segments adjacent to the fused bone were higher than those of Group
      1. Under extension and Group 2, ROM for the fused segment was less than that of
      Group 1; torque, ROM, and stress on both the bodies and facets of superior
      segments adjacent to the fused bone were higher than those of Group 1. These
      analytical results indicate that the muscles and ligaments require greater force
      to achieve cervical motion than the intact spine following anterior cervical
      spine fusion. In addition, ROM and stress on the bodies and facets of the joint
      segments adjacent to the fused bone were significantly increased. Under flexion,
      the neutral axis of the stress on the adjacent segment moved backward, and the
      stress on the bodies of the segments adjacent to the fused bone increased. These
      comparative results indicate that increased stress on the adjacent segments is
      caused by stress-shielding effects. Furthermore, increased stress and ROM of the
      adjacent segments after long-term bone fusion may accelerate degeneration in
      adjacent segment.

PMID- 23140761
TI  - Long-term effect of resistant starch on cancer risk in carriers of hereditary
      colorectal cancer: an analysis from the CAPP2 randomised controlled trial.
AB  - BACKGROUND: Observational studies report that higher intake of dietary fibre (a
      heterogeneous mix including non-starch polysaccharides and resistant starches) is
      associated with reduced risk of colorectal cancer, but no randomised trials with
      prevention of colorectal cancer as a primary endpoint have been done. We assessed
      the effect of resistant starch on the incidence of colorectal cancer. METHODS: In
      the CAPP2 study, individuals with Lynch syndrome were randomly assigned in a two
      by-two factorial design to receive 600 mg aspirin or aspirin placebo or 30 g
      resistant starch or starch placebo, for up to 4 years. Randomisation was done
      with a block size of 16. Post-intervention, patients entered into double-blind
      follow-up; participants and investigators were masked to treatment allocation.
      The primary endpoint for this analysis was development of colorectal cancer in
      participants randomly assigned to resistant starch or resistant-starch placebo
      with both intention-to-treat and per-protocol analyses. This study is registered,
      ISRCTN 59521990. FINDINGS: 463 patients were randomly assigned to receive
      resistant starch and 455 to receive resistant-starch placebo. At a median follow
      up 52.7 months (IQR 28.9-78.4), 53 participants developed 61 primary colorectal
      cancers (27 of 463 participants randomly assigned to resistant starch, 26 of 455
      participants assigned to resistant-starch placebo). Intention-to-treat analysis
      of time to first colorectal cancer showed a hazard ratio (HR) of 1.40 (95% CI
      0.78-2.56; p=0.26) and Poisson regression accounting for multiple primary events
      gave an incidence rate ratio (IRR) of 1.15 (95% CI 0.66-2.00; p=0.61). For those
      completing 2 years of intervention, per-protocol analysis yielded a HR of 1.09
      (0.55-2.19, p=0.80) and an IRR of 0.98 (0.51-1.88, p=0.95). No information on
      adverse events was gathered during post-intervention follow-up. INTERPRETATION:
      Resistant starch had no detectable effect on cancer development in carriers of
      hereditary colorectal cancer. Dietary supplementation with resistant starch does
      not emulate the apparently protective effect of diets rich in dietary fibre
      against colorectal cancer. FUNDING: European Union, Cancer Research UK, Bayer
      Corporation, National Starch and Chemical Co, UK Medical Research Council,
      Newcastle Hospitals Trustees, Cancer Council of Victoria Australia, THRIPP South
      Africa, The Finnish Cancer Foundation, SIAK Switzerland, and Bayer Pharma.

PMID- 23140765
TI  - Differential regulation of nuclear factor-kappa B subunits on epidermal
      keratinocytes by ultraviolet B and tacrolimus.
AB  - Modulation of nuclear factor-kappa B (NF-kappaB) expression has important
      clinical implications including anti-inflammation. Recently, we have shown that
      direct regulation of NF-kappaB/p65 subunit may account for tacrolimus ointment's
      remarkable clinical efficacy on treating inflammatory dermatoses. However, NF
      kappaB is a dimeric transcription factor formed by hetero- or homodimeration of
      the five Rel family proteins. The complete operational scheme of different NF
      kappaB subunits remains obscure. It has been shown that homodimers consist of NF
      kappaB/p50 may serve an inhibitory role in suppressing inflammation while dimers
      consisting of NF-kappaB/p65 activate inflammatory pathway. Our current study
      aimed to explore the effects of ultraviolet B (UVB) on epidermal keratinocytes in
      terms of specific NF-kappaB subunits NF-kappaB/p50 and NF-kappaB/p65.
      Additionally, the effects of tacrolimus on differential regulation of NF-kappaB
      subunits of UVB irradiated keratinocytes were also investigated. Our result
      showed that UVB sequentially regulated the activities of different subunits of NF
      kappaB: the activity of NF-kappaB/p50 was downregulated in the early stage (6
      hours), followed by upregulation of NF-kappaB/p65 in the later stage (12 hours).
      The results from immunofluorescence, immunocytochemical, and immunohistochemical
      analyses indicated that the nuclear expression of NF-kappaB/p50 could be seen
      constitutively while the nuclear expression of NF-kappaB/p65 could only be seen
      after UVB irradiation. Furthermore, treatment with tacrolimus didn't affect the
      nuclear activation and translocation of NF-kappaB/p50, while the UVB induced NF
      kappaB/p65 nuclear expression was suppressed by tacrolimus. In summary, we have
      shown that UVB irradiation sequentially regulated different NF-kappaB subunits.
      The clinical efficacy of tacrolimus may be attributed to its specific regulatory
      effect on NF-kappaB/p65 but not NF-kappaB/p50 of the NF-kappaB pathway.

PMID- 23140767
TI  - Salmonella/rotavirus coinfection in hospitalized children.
AB  - This study's aim was to analyze the characteristics and severity of acute
      gastroenteritis related to infection with rotavirus (group R), nontyphoid
      Salmonella (NTS; group S), and infection with both rotavirus and Salmonella
      (group B) in children in southern Taiwan in order to improve diagnosis and
      expedite appropriate management. The medical records of children admitted between
      October 2002 to September 2008 for acute gastroenteritis related to rotavirus,
      NTS, or coinfection were collected and analyzed.Among 2040 reviewed medical
      records, 40 patients were infected with both pathogens, while 501 cases were
      infected with rotavirus alone and 189 were infected with NTS alone. There were no
      significant differences between the three groups in terms of age at admission or
      sex. The age distribution of the reviewed cases revealed that children between
      the ages of 12-24 months comprised the largest proportion of cases in each group.
      Higher concentrations of fecal leukocytes and fecal pus cells and longer
      hospitalizations were observed in group B in comparison with groups S and R (p <
      0.05). Clinical severity was significantly higher in groups B and S than group R
      (p < 0.05). A proportional association was found between the monthly case number
      of rotavirus infections and the mean monthly temperature difference in southern
      Taiwan (r = 0.9248; p < 0.0001). In summary, concomitant rotavirus infection with
      NTS infection did not affect the clinical manifestations of the reviewed
      patients. Rotavirus infection was less severe in most clinical manifestations,
      but vomiting was more severe in rotavirus-infected patients. Positive fecal
      leukocytes and positive fecal pus cells were more frequent during coinfection.
      There was a strong positive relationship between the incidence of rotavirus
      gastroenteritis and the mean monthly temperature difference.

PMID- 23140768
TI  - Neonatal intensive care unit-specific screening criteria for retinopathy of
      prematurity.
AB  - This study investigated the incidence of retinopathy of prematurity (ROP) and its
      risk factors in a tertiary referral hospital in Taiwan to evaluate the
      applicability of the ROP screening guidelines published by the American Academy
      of Pediatrics, American Academy of Ophthalmology, and American Association for
      Pediatric Ophthalmology and Strabismus in 2006 (2006 guidelines). A pediatric
      ophthalmologist applied the 2006 guidelines to screen for ROP and to treat with
      laser photocoagulation in each case. We retrieved all records of premature
      infants referred for ROP screening at the hospital during 2004 to 2008.
      Univariate logistic regression analysis was applied firstly to identify factors
      correlating with stage 3 ROP or with laser treatment, and then those significant
      (p < 0.05) risk factors were analyzed by multivariate logistic regression. In the
      138 male and 118 female premature infants in this study, mean gestation age was
      30.8 +/- 2.8 weeks, and mean birth weight was 1464.7 +/- 434.2 g. The percentage
      of infants with ROP in at least one eye was 38.7%. Thirty two (12.5%) had ROP
      stage 3 or higher in at least one eye. Multivariate logistic regression analysis
      showed that the best predictors of type 1 pre-threshold ROP (requiring laser
      treatment) were young gestational age, low birth weight and male gender. As
      medical care of extremely premature infants improves, timely identification and
      treatment of conditions such as ROP are essential. Although the incidence of ROP
      in this institute was comparable to that in developing countries and higher than
      that in developed countries, the 2006 guidelines originally developed for a
      United States population were still applicable. However, the 2006 guidelines
      should be modified for a Taiwan population by considering gender.

PMID- 23140769
TI  - Symptomatological and cognitive correlates of vascular comorbidity in older
      elderly (at least 75 years old) men with major depressive disorder.
AB  - Depression is a common geriatric psychiatric disorder increasing with age among
      elderly people (>= 75 years old), especially those with medical comorbidities.
      They have higher suicide rates than younger men, but these are paid less
      attention. Elderly men (n=141) who were newly admitted residents of the Veterans'
      Home in Tainan, Taiwan from 2004 to 2006 were recruited and screened for major
      depression. Specialist physicians obtained past histories of medical illnesses
      through chart reviews, interview, and health examinations. Fifty-nine of the 141
      elderly people had major depression and participated in this study. Thirty-nine
      men in the group with vascular comorbidities (VC), and 20 in the group without
      (NVC) vascular comorbidities were compared. The VC group had more time
      orientation impairment, greater psychomotor retardation, and diminished
      concentration/decision-making than did the NVC group. Psychomotor retardation and
      other cognitive function impairments (e.g., concentration and decision-making)
      are characteristic manifestations among patients with major depression and
      vascular comorbidity compared with those without vascular comorbidity.

PMID- 23140770
TI  - Bladder management of patients with spinal cord injuries sustained in the 2008
      Wenchuan earthquake.
AB  - This study's aim is provide an overview of the patients who suffered spinal cord
      injury (SCI) after the magnitude 8.0 Wenchuan earthquake, including each
      patient's demographic and epidemiological characteristics, bladder management
      status, and quality of life (QOL). We also assessed the relationships between
      bladder management methods, symptomatic urinary tract infection (SUTI), and QOL.
      Two years after the 2008 Wenchuan earthquake, a cross-sectional face-to-face
      survey was conducted on 180 patients with SCI. A self-administered questionnaire
      and the WHOQOL-BREF assessment were used to assess injury-related information,
      bladder management methods, and SUTI. Statistical analysis was performed using
      the Chi-square test and analysis of variance. A p value <0.05 was considered
      statistically significant. This study found that a male-to-female ratio of
      approximately 1.2:1, including 98 (54.4%) male patients and 82 (45.6%) female
      patients. Thoracic-level injuries were seen in 82 patients (45.56%), 60 (33.33%)
      patients had lumbar-level injuries, 18 (8.33%) patients had thoracolumbar-level
      injuries, and a small number of patients had cervical- or sacral-level injuries.
      Sixty-two patients (34.44%) demonstrated normal voiding, 65 (36.11%) required
      manually assisted voiding, 29 (16.11%) required catheterization, and 24 (13.33%)
      used aurine-collecting apparatus. The prevalence of SUTI was 43.89%. Patients who
      emptied their bladder via manually assisted voiding, catheterization, or with the
      use of a urine-collecting apparatus demonstrated higher rates of SUTI compared
      with patients who voided normally (p < 0.05); the patients who required
      catheterization had higher rates of SUTI compared with patients who required
      manually assisted voiding (p < 0.05). When manually assisted voiding and
      catheterization were compared with the use a urine-collecting apparatus, no
      statistically significant differences were observed in terms of the risk of
      developing SUTI. The patients in this study demonstrated low scores on the WHOQOL
      BREF physical domain (11.61 +/- 3.80), psychological domain (10.11 +/- 3.63),
      social domain (11.46 +/- 2.84), and environmental domain (11.86 +/- 2.51). The
      patients who reported normal voiding also demonstrated the best QOL in terms of
      physical, psychological, and social component scores (p < 0.05). In conclusion,
      the percentage of women in this study is higher than that reported in other
      studies on traumatic causes of SCI. Patients who suffered SCI following the
      Wenchuan earthquake demonstrate poor bladder management status and are unable to
      take advantage of urodynamic testing that is used to monitor the functional state
      of the bladder. This study's findings indicate that bladder management methods
      influence the rate of SUTI and the QOL of patients with SCI. Caring for SCI
      patients following a disaster requires comprehensive long-term planning. Bladder
      management of patients with SCI is essential for improving the QOL of these
      patients.

PMID- 23140771
TI  - Modified basket plate for inferior patellar pole avulsion fractures: a report of
      three cases.
AB  - In patients who have sustained an avulsion fracture of the inferior patellar
      pole, the extensor mechanism is disrupted and should be repaired. The normal
      height of the patella can be maintained by preserving the patellar pole, but
      fractures of the inferior pole of the patella are not easy to reduce and fix
      firmly. In contrast with partial patellectomy, which requires postoperative
      immobilization, internal fixation with a basket plate allows for immediate
      mobilization and early weight-bearing. Owing to the unavailability of the basket
      plate in Taiwan, we have modified the plate with the titanium mesh as a possible
      alternative. We present three cases of this modified basket plate, which took
      place between 2008 and 2010. This technique avoided long-term immobilization of
      the knee with good clinical results.

PMID- 23140772
TI  - CEA-producing urothelial cell carcinoma with metastasis presenting as a rectal
      adenocarcinoma.
AB  - This is a case study of a 61-year-old male who presented with difficult
      defecation for 1 month. A circumferential submucosal rectal tumor was noted on a
      digital rectal examination and colonoscopy. Laboratory examination revealed high
      serum levels of carcinoembryonic antigen (CEA; 43.75 ng/mL) and carbohydrate
      antigen 19-9 (CA19-9; 11,790 U/mL). In addition, tumor biopsies revealed a poorly
      differentiated adenocarcinoma of the rectum with intact mucosa. The patient had
      history of advanced stage-T2 urothelial cell carcinoma of bladder, which had been
      downstaged to T0 by neoadjuvant chemotherapy followed by radical cystectomy 1
      year prior. After investigating the initial bladder tumor specimens, a small
      portion of the tumor with high CEA expression comparable to the submucosal rectal
      tumor was found. The size of the tumor was reduced and the levels of the tumor
      markers decreased after administering FOLFIRI chemotherapy targeted at the
      adenocarcinoma. Although neoadjuvant chemotherapy may have a selective pressure
      to eliminate most urothelial cell carcinoma, physicians should be aware that it
      can lead to rectal metastasis via CEA-producing components.

PMID- 23140773
TI  - Acute human immunodeficiency virus infection presenting as mononucleosis-like
      illness, acute hepatitis, and aseptic meningoencephalitis.

PMID- 23140774
TI  - Vascular modification by electropermeabilization.

PMID- 23140775
TI  - Job description: nurse, 2010.

PMID- 23140776
TI  - Moral distress and nurse-physician relationships.

PMID- 23140777
TI  - Physicians and advanced practice registered nurses: the supervisor-employer
      relationship.

PMID- 23140779
TI  - AMA Code of Medical Ethics Opinion on Nurses.

PMID- 23140778
TI  - Zero-tolerance for hospital romance?

PMID- 23140780
TI  - Perceptions of Teamwork in the OR: Roles and Expectations.

PMID- 23140781
TI  - To cath or not to cath?

PMID- 23140782
TI  - Safety in collaboration: upholding standards of care.

PMID- 23140783
TI  - The primary care shortage, nurse practitioners, and the patient-centered medical
      home.

PMID- 23140784
TI  - Gender diversity and nurse-physician relationships.

PMID- 23140785
TI  - The Medical Team Model, the Feminization of Medicine, and the Nurse's Role.

PMID- 23140787
TI  - About the contributors.

PMID- 23140786
TI  - State-mandated collaboration for nurse practitioners.

PMID- 23140788
TI  - Tissue-engineered tubular graft for urinary diversion after radical cystectomy in
      rabbits.
AB  - BACKGROUND: Clinically, using ileal conduit for urinary diversion often caused
      many serious complications. Tissue engineering technology may offer an
      alternative method for urinary diversion after radical cystectomy. In this study,
      we aimed to make a tissue-engineered tubular graft (TETG) using bladder
      epithelial cells and bladder acellular matrix (BAM) for urinary diversion in
      rabbits. METHODS: Bladder epithelial cells of rabbit were cultivated and expanded
      in vitro, which were then seeded on BAM and cultured for 7 d. Then, cell-seeded
      grafts of 4 cm length and 0.8 cm diameter were used to make TETGs and transferred
      into the omentum for 2 wk before urinary diversion. In the experimental group,
      bladders of the rabbits were removed. The proximal ends of TETGs were anastomosed
      with ureters, and the distal ends were anastomosed with the abdominal stomas. In
      the control group, TETGs were constructed using unseeded BAM. Newly formed tissue
      structures were functionally and microscopically evaluated using urography and
      immunohistochemistry at 1, 2, 4, and 8 wk after operation, respectively.
      Histologic examination with hematoxylin and eosin staining was conducted to
      assess tissue regeneration. Immunohistochemistry was performed with AE1/AE3,
      uroplakin IIIa, and zonula occludens 1 (ZO-1) antibodies. RESULTS: All animals
      were alive in the experimental group. Hematoxylin and eosin staining showed
      epithelial coverage in TETG. Immunohistochemistry showed positive stain with
      AE1/AE3, uroplakin IIIa, and ZO-1, which indicated mature and functional
      epithelial cells on the lumen of TETG. Intravenous urography showed that there
      were no obstructions in TETGs. In the control group, four rabbits were dead
      within 2 wk, and scar formation, atresia, and severe hydronephrosis were found.
      CONCLUSIONS: It was feasible that TETG constructed using bladder epithelial cells
      and BAM for urinary diversion after radical cystectomy in rabbits.

PMID- 23140790
TI  - Beyond herniation: which patients are salvageable?

PMID- 23140791
TI  - Prehospital Emergency Nursing students' experiences of learning during
      prehospital clinical placements.
AB  - Clinical placements play an important role in learning a new profession, but
      students report about poor placement experiences. Standards have been laid down
      for improvements within clinical training in Prehospital Emergency Nursing
      programmes in Sweden, but no studies have been carried out in this field in a
      Swedish context. The purpose of this study was thus to describe the experiences
      of Prehospital Emergency Nursing (PEN) students of their clinical placement and
      the effect on their learning process. Data were collected in 28 individual
      interviews and analyzed in accordance with Flanagan's Critical Incident
      Technique. Three main areas emerged: the professional clinical supervisor, the
      clinical placement setting and the learning strategy. All these areas played a
      significant role in the PEN students' learning progress and development into a
      new professional role. The choice of clinical supervisor (CS) and clinical
      placement is important if PEN students' learning is to be an effective and
      positive experience. The prehospital environment is unique and can have positive
      and negative effects on student learning depending on the support and structure
      given during their clinical placement. A learning strategy based on reflective
      dialogue, CS continuity and a learning structure based on the prehospital
      environment is presented. 

PMID- 23140789
TI  - Stabilizing endothelium of donor hearts with fusogenic liposomes reduces
      myocardial injury and dysfunction.
AB  - BACKGROUND: Myocardial injury after heart transplantation is a consequence of
      pathophysiologic events initiated by local ischemia/reperfusion injury that is
      further aggravated by the inflammatory response due to blood exposure to the
      pump's artificial surfaces during cardiopulmonary bypass. The purpose of the
      present study was to determine the effectiveness of fusogenic lipid vesicles
      (FLVs) in enhancing the cardioprotective effect of St. Thomas organ preservation
      solution (ST). We hypothesized that donor hearts preserved with ST+FLVs will
      stabilize the endothelium during reperfusion, which, in turn, will reduce both
      endothelial barrier dysfunction and myocardial damage. METHODS: To examine the
      effect of ST+FLVs therapy in vitro, C3b deposition and adhesion molecule
      expression studies were performed on human umbilical vein endothelial cells
      challenged with plastic contact-activated plasma. To assess the therapy in vivo,
      a cervical heterotopic working heart transplantation model in rats was used.
      Donor hearts were preserved for 1 h at 27 degrees C (15 min) and 4 degrees C (45
      min) and, after transplantation, were followed up for 2 h. Left ventricular
      function and the blood cardiac troponin I levels were quantified. RESULTS: Human
      umbilical vein endothelial cells treated with ST+FLVs had reduced C3b deposition
      and expression of adhesion molecules compared with ST alone (P < 0.05). Donor
      hearts receiving ST+FLVs therapy had reduced left ventricular dysfunction and
      cardiac troponin I compared with ST alone. CONCLUSIONS: We concluded that FLVs
      enhanced the cardioprotective effect of ST and reduced postischemic left
      ventricular dysfunction and myocardial damage. The mechanism of protection
      appears to be associated with the stabilization of endothelial cell membranes
      owing to incorporation of FLV-derived lipids.

PMID- 23140792
TI  - Sesamoid complex disruption as a cause of hallux valgus: report of three cases.
AB  - Hallux valgus is perhaps the most common forefoot deformity, usually related to
      genetic factors, gender and footwear habits. The current cases represent an
      unusual etiology of the syndrome due to sesamoid ligamentary damage and inter
      sesamoid ligament rupture. One of the cases was treated surgically by excision of
      the non-united lateral sesamoid and reconstruction of the intermetatarsal
      ligament. Another one was treated by a Wilson-like osteotomy. The third one was
      conservatively treated by casting. In these cases the hallux valgus angle
      declined following treatment.

PMID- 23140794
TI  - [Objective impact factor. Together we can, go for it].

PMID- 23140795
TI  - [The reality of cares to the family of the critical patient in Spain: action must
      be taken now].

PMID- 23140793
TI  - Novel valosin containing protein mutation in a Swiss family with hereditary
      inclusion body myopathy and dementia.
AB  - Inclusion body myopathy associated with Paget's disease of the bone and
      frontotemporal dementia is a rare but highly penetrant autosomal dominant
      progressive disorder linked to mutations in valosin containing protein (VCP).
      Here, we characterize a novel mutation in the linker 1 domain of VCP leading to
      inclusion body myopathy and/or frontotemporal dementia in 3 generations of a
      Swiss family. A detailed history of several years of clinical follow-up and
      electrophysiological, radiological and pathological findings are presented. Five
      out of 6 individuals suffered from progressive myopathy and 2 out of 6 from
      frontotemporal dementia, respectively. A radiologically suspected Paget's disease
      of the bone could not been confirmed at autopsy. This case study illustrates that
      only a subset of individuals shows the full triad of the disease complex and that
      clinicopathological findings are - when interpreted apart from familial history -
      hard to distinguish from sporadic inclusion body myositis.

PMID- 23140796
TI  - Internal Carotid Artery Strains During High-Speed, Low-Amplitude Spinal
      Manipulations of the Neck.
AB  - OBJECTIVE: The primary objective of this study was to quantify the strains
      applied to the internal carotid artery (ICA) during neck spinal manipulative
      treatments and range of motion (ROM)/diagnostic testing of the head and neck.
      METHODS: Strains of the ICA (n = 12) were measured in 6 fresh, unembalmed
      cadaveric specimens using sonomicrometry. Peak and average strains of the ICA
      obtained during cervical spinal manipulations given by experienced doctors of
      chiropractic were compared with the corresponding strains obtained during ROM and
      diagnostic testing of the head and neck. RESULTS: Peak and average strains of the
      ICA for cervical spinal manipulative treatments were significantly smaller (P <
      .001) than the corresponding strains obtained for the ROM and diagnostic testing.
      All strains during ROM and treatment testing were dramatically smaller than the
      initial failure strains of the ICA. CONCLUSIONS: This study showed that maximal
      ICA strains imparted by cervical spinal manipulative treatments were well within
      the normal ROM. Chiropractic manipulation of the neck did not cause strains to
      the ICA in excess of those experienced during normal everyday movements.
      Therefore, cervical spinal manipulative therapy as performed by the trained
      clinicians in this study, did not appear to place undue strain on the ICA and
      thus does not seem to be a factor in ICA injuries.

PMID- 23140797
TI  - The No-Prop algorithm: a new learning algorithm for multilayer neural networks.
AB  - A new learning algorithm for multilayer neural networks that we have named No
      Propagation (No-Prop) is hereby introduced. With this algorithm, the weights of
      the hidden-layer neurons are set and fixed with random values. Only the weights
      of the output-layer neurons are trained, using steepest descent to minimize mean
      square error, with the LMS algorithm of Widrow and Hoff. The purpose of
      introducing nonlinearity with the hidden layers is examined from the point of
      view of Least Mean Square Error Capacity (LMS Capacity), which is defined as the
      maximum number of distinct patterns that can be trained into the network with
      zero error. This is shown to be equal to the number of weights of each of the
      output-layer neurons. The No-Prop algorithm and the Back-Prop algorithm are
      compared. Our experience with No-Prop is limited, but from the several examples
      presented here, it seems that the performance regarding training and
      generalization of both algorithms is essentially the same when the number of
      training patterns is less than or equal to LMS Capacity. When the number of
      training patterns exceeds Capacity, Back-Prop is generally the better performer.
      But equivalent performance can be obtained with No-Prop by increasing the network
      Capacity by increasing the number of neurons in the hidden layer that drives the
      output layer. The No-Prop algorithm is much simpler and easier to implement than
      Back-Prop. Also, it converges much faster. It is too early to definitively say
      where to use one or the other of these algorithms. This is still a work in
      progress.

PMID- 23140798
TI  - Retrieval of iatrogenic intravascular foreign bodies.
AB  - Malposition, embolization, fracture, and migration of endovascular devices are
      unfortunate consequences of endovascular intervention and will be encountered at
      some point by nearly every practitioner. The existing literature on foreign body
      retrieval consists of large single-institution series and case reports. We
      provide an overview of this recent literature, clarifying what devices are being
      lost, what symptoms occur as a result, and how retrieval is being performed. We
      have identified all case series and case reports since the year 2000, summarized
      the results, and made some general observations and recommendations that may be
      useful to the practitioner faced with the prospect of retrieving a fractured
      medical device, malpositioned coil, or migrated inferior vena cava filter.

PMID- 23140799
TI  - Effect of endovascular and open abdominal aortic aneurysm repair on thrombin
      generation and fibrinolysis.
AB  - BACKGROUND: Abdominal aortic aneurysm (AAA) is associated with a prothrombotic
      diathesis that may increase the risk of cardiovascular events. This diathesis is
      exacerbated in the short term by open aneurysm repair (OAR) and endovascular
      aneurysm repair (EVAR). However, the effect of EVAR and OAR on coagulation and
      fibrinolysis in the medium and long term is poorly understood. The purpose of
      this study was to investigate the medium-term effects of EVAR and OAR on thrombin
      generation, neutralization, and fibrinolysis. METHODS: Prothrombin fragment
      (PF)1+2, thrombin antithrombin (TAT) complex, plasminogen activator inhibitor
      (PAI) activity, and tissue-plasminogen activator (t-PA) antigen were measured in
      eight age-matched controls (AMCs), 29 patients with AAA immediately before
      (preoperatively) and 12 months after EVAR (post-EVAR), and in 11 patients at a
      mean of 16 months after OAR (post-OAR). RESULTS: Preoperatively, PF1+2 levels
      were significantly higher in patients with AAAs than in AMC. PF1+2 levels post
      EVAR and post-OAR were significantly lower than preoperative values and similar
      to AMC. There was no significant difference in TAT, PAI, or t-PA between AMC, AAA
      preoperatively, and post-EVAR. Post-OAR, PAI activity was significantly higher
      than in preoperative patients. CONCLUSIONS: AAA is associated with increased
      thrombin generation without upregulation of fibrinolysis. The prothrombotic,
      hypofibrinolytic diathesis observed in patients with AAA returns toward normal in
      the medium term after EVAR and OAR, although there is a trend toward decreased
      fibrinolysis post-OAR.

PMID- 23140800
TI  - A survey of student nurses' and midwives' experiences of learning to use
      electronic health record systems in practice.
AB  - AIM: The study aimed to investigate student nurses' and midwives' experiences of
      learning to use electronic health records (EHR) in practice. BACKGROUND: Good
      record keeping and documentation are integral to nursing and midwifery practice.
      As EHRs become more widespread, student nurses and midwives need opportunities to
      access and learn how to use them in practice. METHOD: A survey of nursing and
      midwifery students was conducted using questionnaires (n = 215) and three focus
      groups: one with midwifery students (n = 6); one with mental health nursing
      students (n = 5) and one with adult nursing students (n = 6). The University
      research ethics committee approved the study. The questionnaire data were
      analysed using SPSS v19. The focus group data were analysed thematically
      following transcription. RESULTS: The results presented relate to two themes: 1)
      Preparation for using EHRs and skills development; 2) Access to EHRs and
      involvement. Students had variable experiences in relation to opportunities to
      access and use EHRs, training on EHR systems used in practice and guidance from
      mentors. Some mentors had concerns about students' legitimacy to access EHRs and
      verification of students' EHR entries was a challenging issue in some areas.
      CONCLUSION: To promote opportunities for students to develop competence in using
      EHRs in practice, training on EHR systems in use, and clear processes for
      authorised access, are needed. Following the survey, the University and practice
      partners collaboratively established formalised EHR training for students with
      clear governance procedures for access and use.

PMID- 23140801
TI  - Learning through authentic assessment: an evaluation of a new development in the
      undergraduate midwifery curriculum.
AB  - Assessment is a powerful influence on learning, and can form an important
      strategy amongst a variety of teaching and learning approaches. Authentic
      assessment activities are designed to mimic the complexity of 'real world'
      situations that students may encounter in professional life, and require the
      application of a combination of skills related to knowledge, skills and attitude.
      We undertook a small-scale evaluation using a qualitative descriptive design to
      explore the feasibility and usefulness of an authentic assessment item that
      focused on a common clinical scenario in midwifery practice, female
      catheterisation. Seven third year Bachelor of Midwifery students and three
      teaching staff volunteered to participate in the project. During the process the
      students videoed the scenario for peer assessment, developed marking criteria,
      completed an online survey and participated in a focus group. The findings
      demonstrated that the students' confidence, knowledge and skills improved as a
      result of participating in the assessment item and they rated it positively for
      use in the Bachelor of Midwifery curriculum as a means of increasing real world
      assessment activities. It is anticipated that this learning strategy will be
      further refined and integrated in various ways into other clinical midwifery
      subjects in the midwifery curriculum. 

PMID- 23140802
TI  - Valproic acid improved in vitro development of pig cloning embryos but did not
      improve survival of cloned pigs to adulthood.
AB  - The objective was to examine the effects of valproic acid (VPA), a histone
      deacetylase inhibitor, on in vitro and in vivo development of Wuzhishan miniature
      pig somatic cell nuclear transfer (SCNT) embryos. Experiment 1 compared in vitro
      developmental competence of nuclear transfer embryos treated with various
      concentrations of VPA for 24 h. Embryos treated with 2 mM VPA for 24 h had a
      greater rate of blastocyst formation compared with control or embryos treated
      with 4 or 8 mM VPA (21.5% vs. 10.5%, 12.6%, and 17.2%, P < 0.05). Experiment 2
      examined the in vitro developmental competence of nuclear transfer embryos
      treated with 2 mM VPA for various intervals after chemical activation. Embryos
      treated for 24 h had higher rates of blastocyst formation than the control or
      those treated for 4 or 48 h (20.7% vs. 9.2%, 12.1%, and 9.1%, P < 0.05). In
      Experiment 3, an average of 207 (range, 192-216) nuclear transfer embryos from
      the VPA-treated group were transferred to surrogate mothers, resulting in three
      pregnancies. Two of the surrogates delivered a total of 11 live piglets. However,
      for unknown reasons, nine of 11 piglets in the VPA-treated group died within 1 to
      5 d after birth. Untreated control embryos (average, 205; range, 179-225)
      transferred to four surrogate mothers resulted in three pregnancies, two of which
      delivered a total of 12 live offspring, although four of 12 piglets in the VPA
      untreated group died (cause unknown) within 1 to 3 d, whereas eight of the 12
      piglets in the VPA-untreated group survived more than 3 or 4 mo. The average
      birth weight of the two litters from the VPA-treated group tended (P < 0.05) to
      be lower than that from the control groups (551.6 g vs. 675.2 g). In conclusion,
      VPA treatment increased the blastocyst formation rate of SCNT porcine embryos;
      both VPA-treated and the untreated clones developed to term, but offspring from
      VPA-treated embryos had a lower survival to adulthood than those from control
      embryos (18.2% vs. 67.0%; P < 0.05).

PMID- 23140803
TI  - Characterization of folliculogenesis and the occurrence of apoptosis in the
      development of the bovine fetal ovary.
AB  - The aim of this research was to perform in situ quantification, morphometry
      evaluation, and apoptosis analysis of ovarian follicular wall cells in
      mechanically isolated follicles obtained from ovaries of bovine fetuses (Bos
      taurus indicus) between 3 and 9 months of age. Apoptosis was evaluated using the
      terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. The
      number of isolated follicles increased from 3 months onward (102.5 +/- 141.1,
      mean +/- SEM), peaked at 6 months (12855.0 +/- 9030.1), and then decreased by 7
      months (3208.7 +/- 3249.5), consistent with atresia occurring at these stages.
      Follicular density was greatest at 4 months, consistent with a sudden boost in
      follicular activity independent of a corresponding increase in ovarian size.
      Antral follicles were first observed at 5 months. As fetal age increased, there
      was a tendency for the percentage of primordial and primary follicles to
      decrease, and the percentage of secondary follicles to increase. However, the
      high variability (P < 0.05) for all follicle populations up to 5 months of age
      precluded further interpretation of these results. Oocyte diameter increased from
      the primordial (23.6 +/- 4.4 MUm) to the secondary follicular stages (38.0 +/-
      14.9 MUm). Apoptosis was observed in ovaries from all fetal ages analyzed. We
      concluded that preantral follicles could be isolated from bovine fetuses by 3
      months of age, with apoptosis affecting ovarian follicular dynamics throughout
      fetal life.

PMID- 23140804
TI  - Help seeking for drug and alcohol problems among adults age 50 and older: a
      comparison of the NLAES and NESARC surveys.
AB  - BACKGROUND: Due to population aging and generational changes in alcohol and drug
      use, substance use disorders and treatment need are projected to increase among
      adults over 50. We analyzed data from two national surveys conducted 10 years
      apart [(NLAES (1991-1992) and NESARC (2001-2002)] to explore changes in help
      seeking for alcohol and drug problems among adults over age 50. METHODS: Data
      were pooled on help seeking for substance related problems, sociodemographic and
      clinical variables, and services type (i.e., formal and informal). Differences
      between the surveys were assessed, and help seeking among those under age 50 was
      compared to younger individuals; changes in the sociodemographic and clinical
      correlates of help seeking among those over age 50 were examined. RESULTS: Among
      those 50 and older, rates of lifetime help seeking for any substance problem were
      higher in NESARC than NLAES, and percentages of those considering but not getting
      help were also higher in NESARC. Among those 50+, rates of past-year help seeking
      for drug use were higher in NESARC, but among those with lifetime substance use
      disorders, help seeking rates for alcohol and any substance were lower in the
      NESARC. Older help seekers in the NESARC were less likely to be White, more
      likely to be low income, and more likely to be current or former drug users than
      NLAES help seekers. CONCLUSIONS: This study documents increased rates of help
      seeking for substance related problems among those 50 and older and identifies
      cohort differences in profile of past-year help seekers.

PMID- 23140805
TI  - Multidimensional family therapy lowers the rate of cannabis dependence in
      adolescents: a randomised controlled trial in Western European outpatient
      settings.
AB  - BACKGROUND: Noticing a lack of evidence-based programmes for treating adolescents
      heavily using cannabis in Europe, government representatives from Belgium,
      France, Germany, The Netherlands, and Switzerland decided to have U.S.-developed
      multidimensional family therapy (MDFT) tested in their countries in a trans
      national trial, called the International Need for Cannabis Treatment (INCANT)
      study. METHODS: INCANT was a 2 (treatment condition)*5 (time) repeated measures
      intent-to-treat randomised effectiveness trial comparing MDFT to Individual
      Psychotherapy (IP). Data were gathered at baseline and 3, 6, 9 and 12 months
      thereafter. Study participants were recruited at outpatient secondary level
      addiction, youth, and forensic care clinics in Brussels, Berlin, Paris, The
      Hague, and Geneva. Participants were adolescents from 13 through 18 years of age
      with a recent cannabis use disorder. 85% were boys; 40% were of foreign descent.
      One-third had been arrested for a criminal offence in the past 3 months. Three
      primary outcomes were assessed: (1) treatment retention, (2) prevalence of
      cannabis use disorder and (3) 90-day frequency of cannabis consumption. RESULTS:
      Positive outcomes were found in both the MDFT and IP conditions. MDFT
      outperformed IP on the measures of treatment retention (p<0.001) and prevalence
      of cannabis dependence (p=0.015). MDFT reduced the number of cannabis consumption
      days more than IP in a subgroup of adolescents reporting more frequent cannabis
      use (p=0.002). CONCLUSIONS: Cannabis use disorder was responsive to treatment.
      MDFT exceeded IP in decreasing the prevalence of cannabis dependence. MDFT is
      applicable in Western European outpatient settings, and may show moderately
      greater benefits than IP in youth with more severe substance use.

PMID- 23140806
TI  - Lack of information about multiple sclerosis in children can impact parents'
      sense of competency and satisfaction within the couple.
AB  - The psychosocial consequences for parents of children with MS have not been
      studied. OBJECTIVES: to assess aspects of coping with family crisis and
      individual states of distress in couples with a child with MS compared to couples
      of healthy children. METHODS: fifteen couples with a child with MS and 29 couples
      with healthy children were assessed using self-administered scales on anxiety,
      depression, coping, marital and family aspects, quality of life and MS knowledge.
      RESULTS: parents of children with MS were less satisfied with their parenting
      role and had a lower sense of parenting competence than control parents. While
      their depression scores were higher than control parents, they scored within the
      normal range. Mothers of children with MS were more worried than fathers and were
      more likely to use diverse coping strategies. Less knowledge of MS was correlated
      with less satisfaction with the couple relationship and with the quality of
      communication. There was a correlation between limited knowledge about the
      child's illness and the overall sense of competence as a parent. CONCLUSIONS:
      lack of information about MS can impact family functioning, anxiety and parents'
      sense of competency. Parents require support in becoming more knowledgeable about
      MS in order to feel competent and satisfied in their role and to cope
      successfully.

PMID- 23140807
TI  - The dynamics of finger tremor in multiple sclerosis is affected by whole body
      position.
AB  - Multiple sclerosis (MS) is a disease that results in widespread damage to the
      nervous system. One consequence of this disease is the emergence of enhanced
      tremor. This study was designed to (1) compare the tremor responses of persons
      with MS to that of healthy adults and to (2) examine the impact of whole body
      position (i.e., seated/standing) on tremor. Bilateral postural tremor was
      recorded using accelerometers attached to each index finger. Results revealed
      some similarity of tremor between groups in regard to the principal features
      (e.g., presence of peaks in similar frequency ranges). However, significant
      differences were observed with tremor for the MS persons being of greater
      amplitude, more regular (lower ApEn) and more strongly coupled across limbs
      compared to the elderly. The effects of body position were consistent across all
      subjects, with tremor increasing significantly from sitting-to-standing. However,
      the tremor increase for the MS group was greater than the elderly. Overall, the
      tremor for MS group was negatively affected by both this disease process and the
      nature of the task being performed. This latter result indicates that tremor does
      not simply reflect the feed-forward output of the neuromotor system but that it
      is influenced by the task constraints.

PMID- 23140809
TI  - Responsible progress in surgical innovation: a balancing act.

PMID- 23140808
TI  - Prevalence of metabolic syndrome and prediction of diabetes using IDF versus
      ATPIII criteria in a Middle East population.
AB  - This study investigates the prevalence and predictive value of metabolic syndrome
      in Abu Dhabi, using data from the population-based, programme, 'Weqaya'. The
      Weqaya screen included family history of cardiovascular disease (CVD), CVD risk
      factors, random blood glucose (RBG) and HbA1c. Those not previously diabetic but
      at high risk of diabetes (RBG >=11.1 mmol/l or HbA1c >=6.1%) and randomly
      selected normal subjects were followed-up with fasting glucose, oral glucose
      tolerance test (OGTT), HbA1c and fasting triglycerides. In 760 subjects, 325
      (42.8%) were male with a mean age of 41.9 years (SD 13.8). Using World Health
      Organisation (WHO) criteria, 149 (20.2%) were newly diagnosed diabetics. Using
      International Diabetes Foundation (IDF) and Adult Treatment Panel III (ATPIII)
      criteria, metabolic syndrome was present in 29.0% vs. 31.5% of non-diabetics,
      63.4% vs. 64.2% with impaired glucose handling and 78.6% vs. 79.8% with new-onset
      diabetes using OGTT (P<.001). IDF criteria better predicted pre-diabetes and
      diabetes (OR 3.4 P<.001; OR 6.4 P<.001, respectively); ATPIII criteria better
      predicted high CVD risk scores (OR 13.6 P<.001). Whilst IDF and APTIII
      definitions provide similar prevalence rates, they differentially predict
      prediabetes, diabetes and CVD. This ongoing study will enable the longitudinal
      investigation of the development of diabetes and cardiovascular events in this
      population.

PMID- 23140810
TI  - New devices and truly informed consent.

PMID- 23140811
TI  - Prophylactic bariatric surgery.

PMID- 23140812
TI  - Technical skill and informed consent.

PMID- 23140813
TI  - A patient-centered, ethical approach to medical device innovation.

PMID- 23140814
TI  - AMA Code of Medical Ethics ' Opinions on Patenting Procedures and Devices.

PMID- 23140815
TI  - Risks and benefits of innovative off-label surgery.

PMID- 23140816
TI  - Development and use of dynamic spine stabilization devices.

PMID- 23140817
TI  - Liability of industry representatives in the or.

PMID- 23140818
TI  - Encouraging teamwork to decrease surgical complications.

PMID- 23140819
TI  - Deep brain stimulation: calculating the true costs of surgical innovation.

PMID- 23140820
TI  - The Evolving Relationship between Surgery and Medicine.

PMID- 23140821
TI  - Total joint registries: a foundation for evidence-based arthroplasty.

PMID- 23140822
TI  - About the contributors.

PMID- 23140823
TI  - Safety of multikinase inhibitors in metastatic renal cell carcinoma and indirect
      treatment comparisons.

PMID- 23140824
TI  - Sorafenib as third- or fourth-line treatment of advanced gastrointestinal stromal
      tumour and pretreatment including both imatinib and sunitinib, and nilotinib: A
      retrospective analysis.
AB  - BACKGROUND: Tyrosine kinase inhibitors (TKI) improve the outcome of patients with
      advanced gastrointestinal stromal tumour (GIST), but treatment failure is
      frequent, and prognosis then bleak. Smaller trials in this setting suggested
      activity for sorafenib, a multikinase inhibitor of receptor tyrosine kinases and
      RAF serine/threonine kinases. PATIENTS AND METHODS: We retrospectively evaluated
      the efficacy of sorafenib, starting dose 400mg twice daily, in a large community
      based cohort of 124 patients treated in 12 European and one United States (U.S.)
      cancer centre. All but one patient had a WHO performance score 0-2. All had
      failed both imatinib and sunitinib, 68 patients nilotinib and 26 had failed
      investigational therapy, too. RESULTS: Twelve (10%) patients responded to
      sorafenib and 70 (57%) patients achieved disease stabilisation. Sorafenib was
      moderately tolerated, and toxicity reported in 56% of the patients. Rash, hand
      foot-syndrome and diarrhea occurred frequently. Sorafenib dosage was reduced in a
      third of patients, but this did not have an impact on progression-free survival
      (PFS) (p=0.15). Median PFS was 6.4 months (95% confidence interval [CI], 4.6-8.0
      months) and median overall survival (OS) 13.5 months (95% CI, 10.0-21.0 months).
      Patients with a good performance status and those who responded to sorafenib had
      a significant better PFS. CONCLUSION: We conclude that sorafenib is active in
      GIST resistant to imatinib, sunitinib and nilotinib. These results warrant
      further investigation of sorafenib or similar molecules in GIST.

PMID- 23140826
TI  - Derivation and out-of-sample validation of a modeling system to predict length of
      surgery.
AB  - BACKGROUND: We performed a retrospective study to compare the precision of a
      regression model (RM) system with the precision of the standard method of
      surgical length prediction using historical means (HM). METHODS: Data were
      collected on patients who underwent carotid endarterectomy and lower-extremity
      bypass. Multiple linear regression was used to model the operative time length
      (OTL). The precision of the RM versus HM in predicting case length then was
      compared in a validation dataset. RESULTS: With respect to carotid
      endarterectomy, surgeon, surgical experience, and cardiac surgical risk were
      significant predictors of OTL. For lower-extremity bypass, surgeon, use of
      prosthetic conduit, and performance of a sequential bypass or hybrid procedure
      were significant predictors of OTL. The precision of out-of-sample prediction was
      greater for the RM system compared with HM for both procedures. CONCLUSIONS: A
      regression methodology to predict case length appears promising in decreasing
      uncertainty about surgical case length.

PMID- 23140827
TI  - Effects of extracellular pressure and alcohol on the microglial response to
      inflammatory stimulation.
AB  - BACKGROUND: Traumatic brain injury induces a neuroinflammatory response
      frequently associated with increased intracranial pressure. The aim of this study
      was to investigate the effects of alcohol and increased extracellular pressure on
      murine BV-2 microglial proliferation and cytokine responses to lipopolysaccharide
      (LPS) stimulation. METHODS: BV-2 cells were cultured under 0 or 30 mm Hg
      increased extracellular pressure without or with ethanol (100 mmol/L) or LPS (10
      ng/mL) for 24 hours. Cell proliferation was assessed using MTS assay and
      secretion of the proinflammatory cytokines tumor necrosis factor (TNF)-alpha,
      interleukin (IL)-6, and monocyte chemotactic protein (MCP)-1 by enzyme-linked
      immunosorbent assay. RESULTS: Increased pressure and LPS stimulation each
      promoted proliferation. Ethanol pretreatment blocked these effects. Basal TNF
      alpha and IL-6 secretion was at the limits of delectability. Basal MCP-1
      production was stimulated by pressure, which was blocked by ethanol. Even this
      low LPS dose stimulated microglial secretion of TNF-alpha, IL-6, and MCP-1.
      Pressure inhibited LPS-stimulated production of these proinflammatory cytokines,
      while ethanol pretreatment blocked LPS-stimulated cytokine production. The
      combination of pressure and ethanol further reduced TNF-alpha, IL-6, and MCP-1
      secretion by LPS-stimulated microglial cells. CONCLUSION: Alcohol's anti
      inflammatory effects may contribute to the reduced mortality from traumatic brain
      injury that some have described in acutely intoxicated patients, while pressure
      down-regulation of inflammatory cytokine release could create a negative feedback
      that ameliorates inflammation in traumatic brain injury.

PMID- 23140828
TI  - Analyzer-based phase-contrast x-ray imaging of carotid plaque microstructure.
AB  - BACKGROUND: Plaque vulnerability depends, in part, on composition. Imaging
      techniques are needed that can aid the prediction of plaque stability. High
      contrast images of soft-tissue structure have been obtained with x-ray phase
      contrast (PC) imaging. This research investigates multiple image radiography
      (MIR), an x-ray PC imaging technique, for evaluation of human carotid artery
      plaques. METHODS: Carotid plaques were imaged with ultrasound and subsequently
      excised and formalin fixed. MIR imaging was performed. By using synchrotron
      radiation, conventional radiographs were acquired for comparison. Image texture
      measures were computed for soft-tissue regions of the plaques. RESULTS:
      Ultrasound evaluation identified plaques as homogeneous without calcifications.
      MIR images revealed complex heterogeneous structure with multiple
      microcalcifications consistent with histology, and possessed more image texture
      in specific regions than conventional radiographs (P < .05). MIR refraction
      images allowed imaging of the geometric structure of tissue interfaces within the
      plaques, while scatter images contained more texture in soft-tissue regions than
      absorption or refraction images. CONCLUSIONS: X-ray PC imaging better depicts
      plaque soft-tissue heterogeneity than ultrasound or conventional radiographs. MIR
      imaging technique should be investigated further as a viable imaging technique to
      identify high-risk plaques.

PMID- 23140829
TI  - Long-term results and quality of life in patients treated with hemorrhoidectomy
      using two different techniques: Ligasure versus transanal hemorrhoidal
      dearterialization.
AB  - BACKGROUND: Hemorrhoids are the most frequent anal pathology. We evaluated the
      results of 2 techniques at 1 year after surgery. METHODS: The clinical charts and
      data of patients who underwent hemorrhoidectomy between January 2008 and June
      2010 were considered and analyzed. Patients underwent surgery with 2 techniques:
      transanal hemorrhoidal dearterialization (THD) hemorrhoidectomy or LigaSure
      vessel sealing system (Valleylab, Boulder, CO). Patients were chosen randomly to
      receive one technique or the other. The primary objectives were quality of life,
      quality of defecation, and regression of symptoms. RESULTS: Forty-six patients
      treated with THD and 68 patients treated with Ligasure were enrolled in the
      study. No significant differences were observed in the rate of postoperative
      surgical complications or readmissions. Short- and medium-term (1-6 mo) results
      showed that THD patients had a higher rate of pain resolution compared with
      Ligasure patients (P < .05). Functionally, all patients treated with Ligasure
      showed more postoperative constipation despite administration of laxatives than
      patients treated with THD. CONCLUSIONS: THD is an effective technique and is
      associated with the best short-term clinical and surgical outcomes if compared
      with Ligasure.

PMID- 23140830
TI  - Survival after pancreatectomy for pancreatic adenocarcinoma is not impacted by
      performance status.
AB  - BACKGROUND: Patients with the best performance status have the best prognosis
      after resection for pancreatic adenocarcinoma. This study was undertaken to
      determine the impact of performance status on survival after pancreatectomy for
      adenocarcinoma. METHODS: Patients with a Karnofsky Performance Score (KPS) status
      (KPS) >=60 after pancreatectomy for adenocarcinoma were evaluated, and the impact
      of the KPS at 6 weeks after pancreatectomy on survival was determined using
      survival curve analysis. RESULTS: Recurrence was experienced by 84% of patients
      and negatively impacted patient survival. The median overall survival was 12
      months, and the 2-year overall survival was 35%. The KPS after pancreatectomy did
      not impact survival when using survival curve analysis (P = .5740). CONCLUSIONS:
      Performance status for patients with a KPS >=60 after pancreatectomy does not
      impact survival. Patients with pancreatic adenocarcinoma without adjuvant therapy
      have poor overall survival, and KPS after pancreatectomy for adenocarcinoma
      should not be used to withhold therapy for these patients.

PMID- 23140831
TI  - Patients' perceptions of laparoendoscopic single-site surgery: the cosmetic
      effect.
AB  - BACKGROUND: Laparoendoscopic single-site (LESS) surgery can be performed without
      apparent scarring, while maintaining the salutary benefits of conventional
      laparoscopic surgery. The purpose of this study was to compare patients'
      preoperative and postoperative perceptions of LESS surgery. METHODS: Before and
      after undergoing LESS surgery, 120 patients were given questionnaires; their
      responses were assimilated and analyzed. RESULTS: Of 120 patients, 62% were
      female (age, 52 +/- 16.6 y), and 54% had prior abdominal surgery. Preoperatively,
      women and older patients reported heightened appearance dissatisfaction.
      Preoperatively, most patients would not accept more risk, pain, surgery/recovery
      times, and/or costs than associated with standard laparoscopy. Postoperatively,
      patients reported increased satisfaction in their overall and abdominal region
      appearance. Satisfaction was noted by 92%; satisfaction was related significantly
      to scar appearance and cosmesis. CONCLUSIONS: Preoperatively, patients were most
      concerned with safety; postoperatively, patients' concerns shifted to cosmetic
      outcome. LESS surgery provides an opportunity for improved patient satisfaction.

PMID- 23140832
TI  - Inferior pedicle breast reduction: a retrospective review of technical
      modifications influencing patient safety, operative efficiency, and postoperative
      outcomes.
AB  - BACKGROUND: The inferior pedicle technique remains the most popular approach to
      breast reduction in the United States. Modifications to this procedure have
      enhanced versatility, patient safety, and outcome satisfaction in patients with
      all degrees of macromastia. METHODS: A 6-year retrospective review of 241
      patients who underwent bilateral inferior pedicle breast reduction was conducted
      at our institution. Modifications analyzed included methylene blue tattooing to
      provide preoperative landmarks, preoperative hydrodissection to reduce
      intraoperative blood loss, incorporation of inframammary darting to reduce
      tension at the "T-junction," preservation of superomedial volume for enhanced
      medial fullness, and dermatome blade-guided tissue resection. RESULTS:
      Inframammary darting reduced the incidence of wound dehiscence. Preoperative
      hydrodissection reduced intraoperative blood loss by a factor of 2. Dermatome
      blade use reduced operative times at no increased incidence of postoperative
      seromas or hematomas. CONCLUSIONS: Outcomes resulting from these modifications
      appear to be at least comparable to, and perhaps better than, those previously
      reported.

PMID- 23140833
TI  - Designer nucleic acids to probe and program the cell.
AB  - Recent advances in nucleic acid sequencing, structural, and computational
      technologies have resulted in dramatic progress in our understanding of nucleic
      acid structure and function in the cell. This knowledge, together with the
      predictable base-pairing of nucleic acids and powerful synthesis and expression
      capabilities now offers the unique ability to program nucleic acids to form
      precise 3D architectures with diverse applications in synthetic and cell biology.
      The unique modularity of structural motifs that include aptamers, DNAzymes, and
      ribozymes, together with their well-defined construction rules, enables the
      synthesis of functional higher-order nucleic acid complexes from these
      subcomponents. As we illustrate here, these highly programmable, smart complexes
      are increasingly enabling researchers to probe and program the cell in a
      sophisticated manner that moves well beyond the use of nucleic acids for
      conventional genetic manipulation alone.

PMID- 23140834
TI  - Oxidation matters: the ubiquitin proteasome system connects innate immune
      mechanisms with MHC class I antigen presentation.
AB  - During innate immune responses the delicate balance of protein synthesis, quality
      control and degradation is severely challenged by production of radicals and/or
      the massive synthesis of pathogen proteins. The regulated degradation of
      ubiquitin-tagged proteins by the ubiquitin proteasome system (UPS) represents one
      major pathway for the maintenance of cellular proteostasis and regulatory
      processes under these conditions. In addition, MHC class I antigen presentation
      is strictly dependent on an appropriate peptide supply by the UPS to efficiently
      prime CD8(+) T cells and to initiate an adaptive immune response. We here discuss
      recent efforts in defining the link between innate immune mechanisms like
      cytokine and ROS production, the induction of an efficient adaptive immune
      response and the specific involvement of the UPS therein. Cytokines and/or
      infections induce translation and the production of free radicals, which in turn
      confer oxidative damage to nascent as well as folded proteins. In parallel, the
      same signaling cascades are able to accelerate the protein turnover by the
      concomitantly induced ubiquitin conjugation and degradation of such damaged
      polypeptides by immunoproteasomes. The ability of immunoproteasomes to
      efficiently degrade such oxidant-damaged ubiquitylated proteins protects cells
      from accumulating toxic ubiquitin-rich aggregates. At the same time, this innate
      immune mechanism facilitates a sufficient peptide supply for MHC class I antigen
      presentation and connects it to initiation of adaptive immunity.

PMID- 23140835
TI  - A novel post-transcriptional role for ubiquitin in the differential regulation of
      MHC class I allotypes.
AB  - By providing ligands for Cytotoxic T-Lymphocytes (CTL) as well as Natural Killer
      (NK) cells, the HLA-A/B/C MHC class I molecules (MHC-I) play a central role in
      both innate and adaptive immunity. In addition to CTL-mediated recognition of MHC
      peptide complexes, cell surface expression of MHC-I is closely monitored by NK
      cells, whose killer-cell immunoglobulin-like receptors encode activatory and
      inhibitory receptors with specificity for MHC-I. How the cell surface expression
      of MHC-I is tightly controlled is not well understood. In a functional siRNA
      ubiquitome screen to identify E3 ligases involved in MHC-I regulation we recently
      found that MEX-3C, a novel RNA-binding ubiquitin E3 ligase, is responsible for
      the post-transcriptional, HLA-A allotype-specific regulation of MHC-I. MEX-3C
      expression is increased upon NK cell activation and modulates the threshold of
      killing by these cells. We find that MEX-3C binds the 3'-untranslated region of
      HLA-A2 mRNA, inducing its RING-dependent degradation. The RING domain of MEX-3C
      is not required for HLA-A2 cell surface downregulation, but regulates the
      degradation of HLA-A2 mRNA. We have therefore uncovered a novel post
      transcriptional pathway for regulation of HLA-A allotypes and provide a direct
      link between ubiquitination and mRNA decay.

PMID- 23140836
TI  - [Internet as an information source for health in primary care patients and its
      influence on the physician-patient relationship].
AB  - OBJECTIVE: To describe the use of the Internet by primary care patients to seek
      health related information, understand how they are influenced by this
      information, and evaluate its impact on the doctor-patient relationship. DESIGN:
      Cross sectional study, through self-administered survey. SETTING: One urban
      health center in Madrid. PARTICIPANTS: A total of 323 questionnaires were
      collected from patients between 14 and 75 years old who attended a physician's
      office for any reason, excluding illiterate patients and those with neurological
      or psychiatric problems preventing them from completing the survey. MEASUREMENTS:
      Internet usage, ability of the internet to clarify doubts regarding health
      issues, patient lifestyle changes, socio-demographic variables, and physician's
      receptivity to the use of internet by patients. RESULTS: 61% (CI95%: 56%-67%) of
      patients used the Internet as a source of health information: Internet queries
      were able to address health doubts in 92.4% of users, 53.5% reported that the
      Internet changed their thinking about their health in at least one instance, 30%
      made behavioral changes (of which 60.1% discussed these changes with their
      physician), 44.3% had more questions at the physician's office, and 80.8% believe
      that the doctor would be willing to talk about the information found on the
      internet. CONCLUSIONS: Using the Internet to find information about health is
      very common, with positive influence on physician-patient relationship. This may
      be useful for achieving behavioral changes in patients and can be used as a tool
      in medical practice.

PMID- 23140837
TI  - [Comparative analysis of serological tests performed in immigrants in the Lleida
      health area].
AB  - OBJECTIVE: Evaluate the process of screening and detection of HIV, HBV, HCV and
      syphilis in the province of Lleida by determining the proportions of positive
      results in the different groups during one year. DESIGN: Descriptive, multicentre
      study of all the serological tests performed in immigrants and natives attended
      in 2007. SETTING: Province of Lleida (Spain). PARTICIPANTS: 255,410 users. MAIN
      MEASUREMENTS: Age, sex, country of origin and period of residence in Spain, and
      the results for HIV, hepatitis B, hepatitis C and syphilis. We calculated the
      proportions in which a serological test had been requested, and examined the
      association between the rates of positive tests and the geographical area of
      origin, and calculated age-adjusted rates taking the age distribution of the
      native population as the reference. RESULTS: Risk of HBV was 4.6 times higher in
      immigrants than in natives (11.7 times in sub-Saharan Africans). The rate of
      positive syphilis tests was three times higher in the immigrant group. For HIV
      the PR was 2.3 (sub-Saharan Africans 7.4). For hepatitis C the risk was lower in
      immigrants than in natives (PR=0.4). CONCLUSIONS: Immigrants have a higher
      probability of testing positive in screening in hepatitis B, syphilis and HIV.
      The rates differ significantly according to the origin of the immigrant.

PMID- 23140838
TI  - [Elastofibroma dorsi: a series of 4 cases diagnosed in primary care].

PMID- 23140825
TI  - Beyond gel electrophoresis: microfluidic separations, fluorescence burst
      analysis, and DNA stretching.

PMID- 23140839
TI  - [The importance of evaluating health care interventions].

PMID- 23140840
TI  - High and increasing prevalence of inflammatory bowel disease in Finland with a
      clear North-South difference.
AB  - BACKGROUND AND AIM: Inflammatory bowel disease (IBD) prevalence has increased and
      a North-South gradient has been reported. We estimated the nationwide prevalence
      of IBD, ulcerative colitis (UC) and Crohn's disease (CD) in 1993, and prevalence
      of IBD in 2008, and assessed the geographical distribution of IBD in Finland. In
      addition, we investigated the vitamin D levels in a study population from a
      large, nationally representative health examination survey, the Health 2000
      Survey. METHODS: The register study for prevalences included all patients who had
      special reimbursement of medications for IBD in the years 1993 (n=10,958) and
      2008 (31,703). The study for D-vitamin measurement consisted of 6134 persons who
      had participated in the Health 2000 Survey. RESULTS: The nationwide point
      prevalence of IBD in 1993 was 216 per 100,000 inhabitants, and 595 in 2008. In
      1993, the prevalence of UC (177) was fourfold higher than the prevalence of CD
      (38). The prevalence of IBD and UC in Finland increased from South to North. For
      CD, no geographical variation could be demonstrated. In the Health 2000 survey,
      vitamin D levels were lower in Northern than in Southern Finland. CONCLUSIONS:
      Finland belongs to high prevalence area of IBD and this prevalence has increased
      nearly threefold during the past 15 years. A clear North-South gradient has been
      shown for IBD and UC, but not for CD. Slightly lower vitamin D levels in Northern
      Finland may be associated with the observed higher prevalence of IBD there.

PMID- 23140842
TI  - A comparison between customized clear and removable orthodontic appliances
      manufactured using RP and CNC techniques.
AB  - OBJECTIVES: Aim of the research is to compare the orthodontic appliances
      fabricated by using rapid prototyping (RP) systems, in particular 3D printers,
      with those manufactured by using computer numerical control (CNC) milling
      machines. 3D printing is today a well-accepted technology to fabricate
      orthodontic aligners by using the thermoforming process, instead the potential of
      CNC systems in dentistry have not yet been sufficiently explored. MATERIALS AND
      METHODS: One patient, with mal-positioned maxillary central and lateral incisors,
      was initially selected. In the computer aided virtual planning was defined that,
      for the treatment, the patient needed to wear a series of 7 removable orthodontic
      appliances (ROA) over a duration of 21 weeks, with one appliance for every 3
      weeks. A non-contact reverse engineering (RE) structured-light 3D scanner was
      used to create the 3D STL model of the impression of the patient's mouth.
      Numerical FEM simulations were performed varying the position of applied forces
      (discrete and continuous forces) on the same model, simulating, in this way, 3
      models with slice thickness of 0.2 mm, 0.1 mm (RP staircase effect) and without
      slicing (ideal case). To define the areas of application of forces, two
      configuration "i" and "i-1" of the treatment were overlapped. 6 patients to which
      for three steps (3rd, 4th and 5th step) were made to wear aligners fabricated
      starting from physical models by 3D printing (3DP-ROA) and afterwards, for the
      next steps (6th, 7th and 8th step), aligners fabricated starting from physical
      models by CNC milling machine (CNC-ROA), were selected. RESULTS: For the 6
      patients wearing the CNC-ROA, it was observed a best fitting of the aligner to
      the teeth and a more rapid teeth movement than the 3DP-ROA (2 weeks compared to 3
      weeks for every appliance). FEM simulations showed a more uniform stress
      distribution for CNC-ROA than 3DP-ROA. CONCLUSIONS: In this research, 6 different
      case studies and CAD-FEM simulations showed that, to fabricate an efficient clear
      and removable orthodontic aligner, it is necessary to consider a compromise of
      several factors. A lower staircase effect (lower layer thickness) and a higher
      physical prototype accuracy allow a better control of tooth movement.

PMID- 23140841
TI  - Autoantibodies against exocrine pancreas in Crohn's disease are directed against
      two antigens: the glycoproteins CUZD1 and GP2.
AB  - BACKGROUND: Autoantibodies against exocrine pancreas (PAb) have been reported to
      be pathognomonic markers of Crohn's disease (CD). Recently, the glycoprotein GP2
      has been proposed as the exclusive target for PAb but two equally prevalent
      binding patterns can be observed in the indirect immunofluorescence test (IIFT)
      using cryosections of human pancreas: a reticulogranular and a droplet pattern.
      AIM: To identify autoantigens corresponding to the staining patterns. METHODS:
      Different lectins were screened for their ability to immobilize PAb-reactive
      glycoproteins from cell free human pancreas. The glycoproteins were then purified
      via UEA-I affinity chromatography and identified by mass spectrometry. The two
      candidate autoantigens were separately expressed in HEK293 cells, and the
      recombinant cells applied as substrates in IIFT to analyze sera from 96 patients
      with CD, 89 controls and hybridoma supernatants during the generation of murine
      monoclonal antibodies. RESULTS: The UEA-I eluate was able to neutralize PAb
      reactivity of both patterns in IIFT. It contained two major constituents which
      were identified as the glycoproteins CUZD1 and GP2. With the recombinant cells,
      35.4% of the CD patients exhibited positive reactions (CUZD1 alone 19.8%, GP2
      alone 9.4%, and both antigens 6.2%). The reaction with the CUZD1 expressing cells
      was strictly correlated to the reticulogranular pattern, whereas the antibodies
      causing the droplet pattern stained the GP2 expressing cells. Antigen-capture
      ELISA using the newly generated monoclonal antibodies against CUZD1 and GP2
      verified this relationship. CONCLUSIONS: The concordant reactivities of the
      different platforms can be regarded as a proof for the authenticity of the two
      identified autoantigens.

PMID- 23140843
TI  - Short-term effects of transcatheter aortic valve implantation on left atrial
      mechanics and left ventricular diastolic function.
AB  - BACKGROUND: Aortic stenosis (AS) leads to remodeling of the left heart. Strain
      measurements enable the assessment of left atrial (LA) mechanics. The goal of
      this study was to evaluate the short-term effects of transcatheter aortic valve
      implantation (TAVI) on LA myocardial deformation as well as left ventricular (LV)
      diastolic function. METHODS: Thirty-two patients with severe AS were
      prospectively enrolled and examined before and 8.2 +/- 3.3 days after TAVI.
      Speckle-tracking echocardiography of the basal septal and lateral segments of the
      left atrium was performed to determine peak positive strain (R(LA)), strain
      during early diastole (E(LA)), and, if feasible, strain during atrial contraction
      (A(LA)). Assessment of LV diastolic function included standard indices, the
      atrial fraction, and LA volumes. RESULTS: Compared with baseline, the mean atrial
      reservoir (R(LA)) (24.0 +/- 11.2% vs 32.2 +/- 14.0%, P < .001) and conduit
      function (R(LA) - E(LA)) (13.9 +/- 5.5% vs 20.8 +/- 8.1%, P < .001) improved
      significantly after TAVI. There was a significant reduction in deceleration time
      (242 +/- 56 vs 195 +/- 65 msec, P < .001) and an improvement of pulsed-wave
      tissue Doppler-derived E' (5.5 +/- 1.8 vs 7.3 +/- 2.3 cm/sec, P = .01). Regarding
      LA volumes, only the minimal LA volume index changed significantly. In contrast,
      there was no improvement in atrial contraction, that is, contractile function
      (E(LA) - A(LA)) and atrial fraction. Moreover, the E/E' ratio remained unchanged.
      CONCLUSIONS: 8.2 +/- 3.3 days after TAVI, only the reservoir and conduit function
      of the left atrium improved, whereas LA contraction and LA volumes, except for
      the systolic volume index, remained unchanged. This was accompanied by
      improvement of early LV diastolic function, indicating acute recovery of LV
      relaxation and LA function.

PMID- 23140844
TI  - Myocardial deformation in the fetal single ventricle.
AB  - BACKGROUND: In postnatal life, patients with single ventricle (SV) with
      morphologic right ventricles have a worse prognosis than those with morphologic
      left ventricles. The aim of this study was to test the hypotheses that (1) the SV
      in fetuses with SV has decreased longitudinal strain compared with fetuses with
      normal cardiac anatomy, and (2) fetuses with SV right ventricular (RV) morphology
      have decreased strain compared with those with SV left ventricular (LV)
      morphology. METHODS: Fetal echocardiograms with SV RV and SV LV morphology were
      retrospectively compiled. Postprocessing analysis of the dominant ventricle was
      done using syngo Velocity Vector Imaging version 2.0. Peak global longitudinal
      strain (GLS) and global longitudinal strain rate (GL SR) were generated. Both the
      right and left ventricles were analyzed in fetuses with normal cardiac anatomy
      for comparison. RESULTS: Fifty-four fetuses with SV (18 with LV morphology and 36
      with RV morphology) were included in the study and compared with 54 controls
      matched for gestational age. Global longitudinal strain and GL SR were compared
      between fetuses with SV and normal fetuses and among SV subsets. When all four
      categories were compared (normal left ventricle, normal right ventricle, SV left
      ventricle, and SV right ventricle), there was no difference in GLS (P = .49) or
      in GL SR (P = .32) between any of the categories. CONCLUSIONS: Comparable GLS and
      GL SR values between fetal SV of LV or RV morphology, as well as normal fetal
      left and right ventricles, reflect in utero preservation of systolic function of
      the SV heart.

PMID- 23140845
TI  - A review and critique of the statistical methods used to generate reference
      values in pediatric echocardiography.
AB  - Several articles have proposed echocardiographic reference values in normal
      pediatric subjects, but adequate validation is often lacking and has not been
      reviewed. The aim of this study was to review published reference values in
      pediatric two-dimensional and M-mode echocardiography with a specific focus on
      the adequacy of the statistical and mathematical methods used to normalize
      echocardiographic measurements. All articles proposing reference values for
      transthoracic pediatric echocardiography were reviewed. The types of
      measurements, the methods of normalization, the regression models used, and the
      methods used to detect potential bias in proposed reference values were
      abstracted. The detection of residual associations, residual heteroscedasticity,
      and departures from the normal distribution theory predictions were specifically
      analyzed. Fifty-two studies met the inclusion criteria. Most authors (87%) used
      parametric normalization to account for body size, but their approaches were very
      heterogeneous. Linear regression and indexing were the most common models.
      Heteroscedasticity was often present but was mentioned in only 27% of studies.
      The absence of residual heteroscedasticity and residual associations between the
      normalized measurements and the independent variables were mentioned in only 9%
      and 22% of the studies, respectively. Only 14% of studies documented that the
      distribution of the residual values was appropriate for Z score calculation or
      that the proportion of subjects falling outside the reference range was
      appropriate. Statistical suitability of the proposed reference ranges was often
      incompletely documented. This review underlines the great need for better
      standardization in echocardiographic measurement normalization.

PMID- 23140846
TI  - Assessment of left atrial deformation and synchrony by three-dimensional speckle
      tracking echocardiography: comparative studies in healthy subjects and patients
      with atrial fibrillation.
AB  - BACKGROUND: The aim of this study was to examine whether left atrial (LA) strain
      and synchrony can be assessed using three-dimensional (3D) speckle-tracking
      echocardiography (STE) and how 3D STE parameters are modified by atrial
      fibrillation (AF). METHODS: LA peak ventricular systolic longitudinal strain
      (LSs), circumferential strain (CSs), and area strain (ASs) and LA peak pre-atrial
      contraction longitudinal strain, circumferential strain (CSa), and area strain
      were determined using 3D STE, and SDs of times to peaks of regional LA strain
      were calculated as indices of LA dyssynchrony. Three-dimensional speckle-tracking
      was able to measure LA strain in 75 of the 77 healthy subjects and in all 47
      patients with AF (31 with paroxysmal AF [PAF] and 16 with permanent AF). RESULTS:
      The mean time for analysis with 3D STE was 18% shorter than with two-dimensional
      (2D) STE (P < .05). On 3D STE, values of interobserver and intraobserver
      variability of LA strain were <10% and <12%, respectively. LSs, CSs, ASs, and 2D
      STE LSs were reduced in patients with PAF compared with controls, and further
      reductions of these parameters were observed in patients with permanent AF. SDs
      of LSs, CSs, and ASs were similarly larger in patients with PAF and in those with
      permanent AF compared with controls. Patients with PAF showed smaller LA peak pre
      atrial contraction longitudinal strain, CSa, and LA peak pre-atrial contraction
      area strain and larger SDs of CSa and LA peak pre-atrial contraction area strain
      compared with controls. In multivariate analysis, 2D STE LSs (P = .044), LSs (P =
      .040), ASs (P = .007), and CSa (P = .020) were independent predictors of PAF.
      CONCLUSIONS: Three-dimensional speckle-tracking enables the measurement of both
      LA strain and synchrony with excellent reproducibility. Three-dimensional LA
      strain appears to be beneficial compared with 2D LA strain for identifying
      patients with PAF.

PMID- 23140847
TI  - A novel mechanism by which MitraClip implantation may favorably alter the natural
      history of left ventricular remodeling in patients with mitral regurgitation:
      proposed role of the ventricular-valvular loop.

PMID- 23140848
TI  - Transthoracic Doppler echocardiography for detection of stenoses in the left
      coronary artery by use of poststenotic coronary flow profiles: a comparison with
      quantitative coronary angiography and coronary flow reserve.
AB  - BACKGROUND: The aim of this study was to determine whether poststenotic diastolic
      to-systolic velocity ratio (DSVR) assessed by transthoracic Doppler
      echocardiography could accurately identify significant stenoses in the left
      coronary artery. METHODS: A total of 108 patients scheduled for coronary
      angiography because of chest pain or acute coronary syndromes were studied.
      RESULTS: The success rates of peak DSVR (pDSVR) measurements in the distal to mid
      left anterior descending coronary artery and marginal branches of the left
      circumflex coronary artery were 85% and 32%, respectively. With peak coronary
      flow velocity reserve as a reference, pDSVR was significantly higher in arteries
      with normal coronary flow reserve (peak coronary flow velocity reserve >= 2.0)
      compared with arteries with reduced coronary flow reserve (peak coronary flow
      velocity reserve < 2.0) (1.86 +/- 0.32 vs 1.53 +/- 0.31, P < .0001). In
      comparison with quantitative coronary angiography, pDSVR was significantly higher
      in lesions with diameter stenosis < 50% compared with those with diameter
      stenosis of 50% to 75% (1.92 +/- 0.32 vs 1.53 +/- 0.18, P < .0001) or diameter
      stenosis of 76% to 100% (1.43 +/- 0.13, P < .0001). Receiver operating
      characteristic curves showed pDSVR < 1.68 to be the optimal cutoff value for
      identifying both functionally significant stenoses and diameter stenoses >= 50%,
      with sensitivity of 86% and 90%, specificity of 74% and 84%, positive predictive
      value of 51% and 71%, and negative predictive value of 94% and 95%, respectively.
      CONCLUSIONS: Transthoracic pDSVR measurements in the distal to mid left anterior
      descending coronary artery and marginal branches of the left circumflex coronary
      artery had high accuracy for excluding functionally significant stenoses in the
      left coronary artery, as well as for identifying angiographic significant
      stenoses.

PMID- 23140849
TI  - Echocardiography in pulmonary arterial hypertension: from diagnosis to prognosis.
AB  - Pulmonary arterial hypertension is most often diagnosed in its advanced stages
      because of the nonspecific nature of early symptoms and signs. Although clinical
      assessment is essential when evaluating patients with suspected pulmonary
      arterial hypertension, echocardiography is a key screening tool in the diagnostic
      algorithm. It provides an estimate of pulmonary artery pressure, either at rest
      or during exercise, and is useful in ruling out secondary causes of pulmonary
      hypertension. In addition, echocardiography is valuable in assessing prognosis
      and treatment options, monitoring the efficacy of specific therapeutic
      interventions, and detecting the preclinical stages of disease.

PMID- 23140850
TI  - [Evaluation of the written informed consent form in clinical trials].
AB  - PURPOSE: To assess the quality of the written informed consent form (WICF) in
      clinical trials. MATERIAL AND METHODS: Retrospective observational study was
      performed on 50 WICF of clinical trials started between 2010 and 2011. The
      quality of the content of the WICF was assessed using the "Guideline for Good
      Clinical Practice" contained in the CPMP/ICH/135/95 of the European Medicines
      Agency. Legibility indexes were applied to the WICF. RESULTS: The WICF was
      correct in all aspects in 10% of the clinical trial; five sections were correct
      in all WICF: "trial involves research", "trials goals", "participation is
      voluntary and the subject may withdraw at any time without penalty", "study
      personnel with access to medical records" and "documents that identify the
      patient are confidential". Aspects less present were "the subject's
      responsibilities" and "available alternatives". All WICF required clarification
      by the Ethics Committee (EC), with a mean of 4.24 (SD=1.87) changes per WICF. The
      WICF showed good results in the indices of readability. Almost all (98%) of WICF
      were considered with an acceptable readability. CONCLUSIONS: Compliance with
      different aspects that must appear in the WICF is high. Aspects to improve are
      the subject's responsibilities and available alternatives to the clinical trial.
      The complexity of reading the WICF is suitable for the average population. The
      review of the WICF by the EC guarantees the access to comprehensive and
      appropriate information.

PMID- 23140851
TI  - Population declines and heavy metal exposure of Swinhoe's Storm Petrels
      (Oceanodroma monorhis) breeding on the southwest coast of Korea.
AB  - We investigated the population dynamics of globally near-threatened Swinhoe's
      Storm Petrels on Kugul and Chilbal islets where >90% of the world breeding
      population have resided for >25 years. We also determined the levels of six heavy
      metals in the seabird species as a possible factor affecting reproduction. Of the
      892 and 307 marked burrows since 1986, the breeding density of Swinhoe's Storm
      Petrels has changed significantly, based on a 55% decline at Kugul islet, and a
      39% decline at Chilbal islet, suggesting that this species has suffered an
      extensive population decline. Of the individuals studied, five Swinhoe's Storm
      Petrels and two Streaked Shearwaters had >8.0 MUg/g Pb in tissues, which is a
      potentially lethal level in avian species. Given that substantial changes in
      their breeding populations may occur in a limited breeding colony, ecological
      threats including environmental pollutants warrant attention for global
      conservation of these birds.

PMID- 23140852
TI  - Functional composition of Chaetodon butterflyfishes at a peripheral and extreme
      coral reef location, the Persian Gulf.
AB  - The functional composition of reef fish assemblages is highly conserved across
      large biogeographic areas, but it is unknown whether assembly rules hold at
      biogeographical and environmental extremes for coral reefs. This study examined
      the functional composition of butterflyfishes in the Persian Gulf, Musandam
      Peninsula, and Gulf of Oman. Only five species of butterflyfishes were recorded
      during this study, and mostly just in the Gulf of Oman. Unlike most locations in
      the Indo-Pacific where butterflyfish assemblages are dominated by obligate
      corallivores, the only obligate corallivore recorded, Chaetodon melapterus, was
      rare or absent at all locations. The most common and widespread species was
      Chaetodon nigropunctatus, which is shown to be a facultative corallivore. The
      diversity of butterflyfishes in the Persian Gulf is likely to have been
      constrained by its' biogeographical history and isolation, but functional
      composition appears to be further affected by limited abundance of prey corals
      and harsh environmental conditions. 

PMID- 23140853
TI  - Molecular characterization of Mycobacterium tuberculosis isolates from North
      Indian patients with extrapulmonary tuberculosis.
AB  - Genotypic studies are important to understand the molecular epidemiology and
      transmission routes of Mycobacterium tuberculosis. In the first and largest study
      from India, spoligotyping and 24 loci mycobacterial interspersed repetitive units
      (MIRU) were performed to find genetic profiles of 125 M. tuberculosis strains
      isolated from patients with extrapulmonary tuberculosis (EPTB) and their drug
      susceptibility test was performed using BACTEC-MGIT 960. Spoligotyping results
      were compared with the world Spoligotyping Database of Institute Pasteur de
      Guadeloupe (SpolDB4). The spoligotyping results showed that 110 (88%) displayed
      known patterns while 15 (12%) isolates had no matching database. Predominant
      spoligotypes belonged to CAS family (57.27%). The largest clade comprised of 38
      isolates belonging to the CAS1_DEL lineage. Though there was no significant
      association between specific mycobacterial lineage and extrapulmonary site, a
      significantly high (p < 0.001) number of Beijing type isolates (28.6%) were
      isolated from bone and joint samples as compared to cerebrospinal fluid (5%).
      There was a significant association between Beijing family isolates and multi
      drug-resistance, while all MANU genotypes were pan-drug sensitive. The CAS family
      lineage was most prevalent genotype in the EPTB cases in our population.

PMID- 23140854
TI  - Antibody response to Mycobacterium tuberculosis p27-PPE36 antigen in sera of
      pulmonary tuberculosis patients.
AB  - We have expressed, characterized and studied the immune response of mice against
      the Mycobacterium tuberculosis PPE36 protein. This protein encoded by the gene
      Rv2108 is a 27-kDa cell-wall associated protein. Here, we compare the antibody
      isotypes distribution of p27-PPE36 in sera of pulmonary tuberculosis patients and
      in sera from healthy control subjects by enzyme-linked immunosorbent assay
      (ELISA). We detected in the sera of affected individuals a significant increase
      of IgA antibody response, a no significant augmentation of IgM response, a
      complete lack of IgG2, 3, and 4 responses and a weak IgG1 response in a few
      subjects.

PMID- 23140855
TI  - [Depression in general practitioner].
AB  - Identification of Major Depressive Disorder (MDD) can be easily done by asking
      systematically the following questions. During the last month: "Did you lose
      interest and pleasure for the things that you usually like and enjoy?" "Have you
      lost energy, or do you feel abnormally tired or depressed?" Physical symptoms of
      MDD are more frequent for patients supported by general practitioner. Patients
      suffering from a general medical affection are more likely to present a risk of
      MDD. Treatment of MDD for patients suffering from a general medical affection
      must be identical to that of patients not suffering from a medical affection.
      Objective of the antidepressant treatment is the complete remission and not only
      the response. Evaluating precisely the symptoms of depression in pretherapetical
      phase allows to facilitate distinction of side effects of a treatment versus
      residual symptoms of depression. Treatment must be taken during a sufficient
      period: 6 to 9 months for a first Major depressive episode up to entire life for
      the most serious cases of recurrent MDD. Making the patient aware of the main
      side effects of the treatment that he will face rapidly (digestion troubles
      essentially) is a simple way to reduce the risks of early abandon of the
      treatment.

PMID- 23140856
TI  - [Suspicion of meningitis: evaluation of the management in the emergency unit].
AB  - INTRODUCTION: Bacterial meningitis is a diagnosis and therapeutic emergency. It
      is associated with high morbidity and mortality. The objective was to evaluate
      the management of suspicion of meningitis in an emergency unit, following the
      update of recommendations. METHODS: A retrospective observational study was
      conducted between 1st January and 30th June 2009 in the emergency unit of
      Grenoble University Hospital. Inclusion criteria were: patient aged 15 years and
      3 months or older with suspicion of meningitis (fever in the last 24 hours with
      the presence of at least one meningeal or neurological clinical sign), for whom a
      lombar puncture was realized in the 48 hours following the admission. Two
      infectious disease specialists independently evaluated the management of these
      patients in the emergency unit. RESULTS: Sixty-eight patients were included.
      Median time of the lombar puncture was 5.5 hours after admission [25-75
      percentiles, 3.7-8,9]. Median time for antibiotic administration was 6 hours
      after admission [25-75 percentiles, 3.3-8.75]. Lactate prescription was stable
      during the study period (P=0.58) whereas procalcitonin prescription increased
      significantly (P=0.02). The realization of a brain scanner before the lumbar
      puncture was associated with a significant delay in the realization of the lumbar
      puncture (P<0.001), and was not associated with a delay in the prescription and
      administration of antimicrobial treatment. According to the infectious disease
      specialists, an antimicrobial treatment was recommended for 37 patients (54.4%);
      and 35 of them (94.6%) received an antibiotic in the emergency department. Dosage
      of ceftriaxone complied with recommendations in 17.8% of cases. A brain scanner
      was recommended for 33 patients and realized for 25 among them (75.8%). Ten
      patients (28.6%) had a brain scanner whereas it was not recommended. CONCLUSION:
      Time management was in accordance with those found in previous studies, although
      higher than those recommended. Consequently it should be reduced. All
      professionals should be concerned. Staff training and writing of protocols are
      necessary (especially for the treatment and the brain scanner indications).

PMID- 23140857
TI  - [Behavioral addictions].
AB  - Each addictive disorder has specific characteristics. It is essential to consider
      them in order to improve the treatment. However, the combination of behavioral
      addictions and substance use disorders is valid, as showed by the next version of
      the DSM. During the treatment, it is important to evaluate cross, but also
      longitudinal, considering the current problematic behavior, but also the
      problematic behaviors that occurred in the past and that may occur in the future.
      There is indeed a significant risk of switching addiction. The relapse prevention
      must consider this risk and be inclusive.

PMID- 23140859
TI  - Global health ethics at home and abroad.

PMID- 23140860
TI  - With so much need, where do I serve?

PMID- 23140858
TI  - The social network of carbon monoxide in medicine.
AB  - Networking between cells is critical for proper functioning of the cellular
      milieu and is mediated by cascades of highly regulated and overlapping signaling
      molecules. The enzyme heme oxygenase-1 (HO-1) generates three separate signaling
      molecules through the catalysis of heme - carbon monoxide (CO), biliverdin, and
      iron - each of which acts via distinct molecular targets to influence cell
      function, both proximally and distally. This review focuses on state-of-the art
      developments and insights into the impact of HO-1 and CO on the innate immune
      response, the effects of which are responsible for an ensemble of functions that
      help regulate complex immunological responses to bacterial sepsis and
      ischemia/reperfusion injury. HO-1 exemplifies an evolutionarily conserved system
      necessary for the cellular milieu to adapt appropriately, function properly, and
      ensure survival of the organism.

PMID- 23140862
TI  - Caring for patients in low-resource settings.

PMID- 23140861
TI  - Mutually beneficial global health electives.

PMID- 23140863
TI  - Applying themes from research ethics to international education partnerships.

PMID- 23140864
TI  - Sustainable International Partnership Building for Academic Medical Centers:
      Experiences with the Botswana-UPenn Partnership.

PMID- 23140865
TI  - The university of washington pediatric residency program experience in global
      health and community health and advocacy.

PMID- 23140866
TI  - AMA Code of Medical Ethics ' Opinion International Research.

PMID- 23140867
TI  - The Physician-Researcher's Dilemma.

PMID- 23140868
TI  - Global health ethics and professionalism education at medical schools.

PMID- 23140869
TI  - The WHO Clinical Staging System for HIV/AIDS.

PMID- 23140871
TI  - Is international trade impacting health? Challenges for this decade.

PMID- 23140870
TI  - Liability considerations for physician volunteers in the u.s.

PMID- 23140872
TI  - Health Electives in Africa and the Duty to Care in the Age of HIV/AIDS.

PMID- 23140873
TI  - Stigmatization complicates infectious disease management.

PMID- 23140874
TI  - Training for a global state of mind.

PMID- 23140875
TI  - About the contributors.

PMID- 23140876
TI  - Hierarchically multifunctional K-OMS-2/TiO2/Fe3O4 heterojunctions for the
      photocatalytic oxidation of humic acid under solar light irradiation.
AB  - A multifunctional heterojunctioned K-OMS-2/TiO(2)/Fe(3)O(4) (KTF) nanocomposite
      was successfully synthesized using a combination of hydrothermal and co
      precipitation techniques. The resultant sample was characterized by XRD, FESEM,
      TEM, N(2) adsorption, XPS and VSM. Its photocatalytic activity was demonstrated
      in the photocatalytic degradation of humic acid (HA). Morphology characterization
      showed the hierarchical structure of the synthesized material, and XRD results
      revealed that both the rutile and anatase TiO(2) structures are present in the
      sample. The average pore diameters and BET surface area of the synthesized KTF
      heterojunctions were 40 nm and 134.42 m(2)/g, respectively. XPS spectra confirmed
      the presence of Fe(3)O(4) and TiO(2) in the synthesized material, and the
      valences of Mn were kept at +3 and +4 after the grafting of Fe(3)O(4) and TiO(2).
      The synthesized material showed good magnetic response and photocatalytic
      activity under simulated solar light irradiation, and 85.7% of HA was decomposed
      after 120 min in the presence of KTF nanocomposites. The reusability study
      suggested that the magnetic recovered material was stable enough for multiple
      recycling usages, verifying its potential application in water purification.

PMID- 23140877
TI  - Study on the source of polycyclic aromatic hydrocarbons (PAHs) during coal
      pyrolysis by PY-GC-MS.
AB  - Hazardous organic pollutants such as polycyclic aromatic hydrocarbons (PAHs)
      generated during the course of coal pyrolysis are highly mutagenic and
      carcinogenic. The relation between the amount of PAHs from the raw coal and that
      generated from coal pyrolysis were studied. Firstly, three Chinese coals from
      Huolinhe, Ximeng and Fenxi were respectively extracted by dichloromethane, and
      then, online pyrolysis analysis of the raw coals, their extraction residues and
      extracts were carried out respectively by PY (Pyro-probe CDS 5250)-GC-MS. The
      experimental results showed that the PAHs generated from the Huolinhe, Ximeng and
      Fenxi coals in the course of their pyrolysis was 523, 327 and 1707 MUg/g,
      respectively, which were much higher than the free PAHs extracted from their
      corresponding raw coals. The PAHs in the raw coals were dominated by 4,5-ring
      PAHs, while those generated from the coal pyrolysis were dominated by lower-ring
      (2,3-rings) PAHs. A lot of important information about the generation of PAHs
      from residue pyrolysis was also included in the paper which indicated that the
      PAHs were mainly from complex chemical reactions of the coal pyrolysis, and PAHs
      were more likely to be generated from the residue pyrolysis due to the increased
      pores that appeared on the coal surface during the course of extraction
      operation.

PMID- 23140878
TI  - Childcare and overweight or obesity over 10 years of follow-up.
AB  - OBJECTIVE: To investigate the predictive association between preschool childcare
      arrangements and overweight/obesity in childhood. STUDY DESIGN: Children were
      enrolled in a prospective birth cohort in Quebec, Canada (n = 1649). Information
      about childcare obtained via questionnaires to the mothers at ages 1.5, 2.5, 3.5,
      and 4 years was used to compute a main childcare arrangement exposure variable
      (center-based/family-based/care by a relative/nanny). Body mass index was derived
      from measured weights and heights at ages 4, 6, 7, 8, and 10 years and children
      were classified as overweight/obese versus normal weight. Generalized estimating
      equations were used to model the effect of main childcare arrangement (center
      based/family-based/relative/nanny) (vs parental care) on overweight/obesity
      adjusting for several potential confounding factors. RESULTS: Compared with
      parental care, children who attended a center-based childcare (OR: 1.65, 95% CI:
      1.13-2.41) or were cared for by a relative (OR: 1.50; 95% CI: 0.95-2.38, although
      with greater uncertainty) had higher odds of being overweight/obese in childhood
      (4-10 years). Analyses of number of hours additionally suggested that each
      increment of 5 hours spent in either center-based or relative childcare increased
      the odds of overweight/obesity in the first decade of life by 9%. Associations
      were not explained by a wide range of confounding factors, including
      socioeconomic position, breastfeeding, maternal employment, and maternal body
      mass index. CONCLUSION: Overweight/obesity was more frequently observed in
      children who received non-parental care in center-based settings or care by a
      relative other than the parent. "Obesogeonic" features of these childcare
      arrangements should be investigated in future studies.

PMID- 23140879
TI  - The role of radiation therapy in pediatric mucoepidermoid carcinomas of the
      salivary glands.
AB  - OBJECTIVE: To investigate the role of radiation therapy in rare salivary gland
      pediatric mucoepidermoid carcinoma (MEC). STUDY DESIGN: A French multicenter
      retrospective study (level of evidence 4) of children/adolescents treated for MEC
      between 1980 and 2010 was conducted. RESULTS: Median age of the 38 patients was
      14 years. Parotid subsite, low-grade, and early primary stage tumors were
      encountered in 81%, 82%, and 68% of cases, respectively. All except 1 patient
      were treated by tumoral surgical excision, and 53% by neck dissection (80% of
      high grades). Postoperative radiation therapy and chemotherapy were performed in
      29% and 11% of cases. With a median 62-month follow-up, overall survival and
      local control rates were 95% and 84%, respectively. There was 1 nodal relapse.
      Lower grade and early stage tumors had better survival. Postoperative radiation
      therapy and chemotherapy were associated with similar local rates. Patients with
      or without prior cancer had similar outcomes. CONCLUSIONS: Pediatric salivary
      gland MEC carries a good prognosis. Low-intermediate grade, early-stage tumors
      should be treated with surgery alone. Neck dissection should be performed in high
      grade tumors. Radiation therapy should be proposed for high grade and/or advanced
      primary stage MEC. For high-grade tumors without massive neck involvement,
      irradiation volumes may be limited to the primary area, given the risk of long
      term side effects of radiation therapy in children. Pediatric MEC as second
      cancers retain a similar prognosis. Long-term follow-up is needed to assess late
      side effects and second cancers.

PMID- 23140880
TI  - The hypertriglyceridemic waist, waist-to-height ratio, and cardiometabolic risk.
AB  - OBJECTIVE: To investigate whether the hypertriglyceridemic waist (HW) phenotype
      and waist-to-height ratio (WHTR) are associated with cardiometabolic disorders in
      children and adolescents. STUDY DESIGN: This was a cross-sectional design study.
      Anthropometry, biochemical variables, and cardiorespiratory fitness were assessed
      in 234 participants (122 girls) aged 10-19 years from Bedfordshire, United
      Kingdom. The HW phenotype was defined as a waist circumference >=90(th)
      percentile for age and sex, and triglyceride concentrations >=1.24 mmol/L, and a
      high WHTR defined as >0.5. ANCOVA and logistic regression were used in the
      analysis. RESULT: In participants with the HW phenotype, the odds of having high
      cardiorespiratory fitness (mL/kg/min) were lower (0.045; 95% CI 0.01, 0.42), and
      the odds of having low high-density lipoprotein cholesterol (4.41; 1.50, 12.91),
      impaired fasting glucose (3.37; 1.06, 10.72), and >=1 (4.78; 1.32, 17.29) and >=2
      risk factors (7.16; 2.38, 21.54) were higher than those without the phenotype.
      Those with a high WHTR had higher odds of having low high-density lipoprotein
      cholesterol (2.57; 1.11, 5.95), high diastolic blood pressure (3.21; 1.25, 8.25),
      and >=2 risk factors (5.57; 2.05, 15.17) than those with normal WHTR. CONCLUSION:
      The HW phenotype may be a better simple marker than WHTR for identifying children
      and adolescents at risk for cardiometabolic disorders.

PMID- 23140881
TI  - Use of antibiotics during pregnancy increases the risk of asthma in early
      childhood.
AB  - OBJECTIVES: To investigate the hypothesis that mother's use of antibiotics in
      pregnancy could influence asthma and eczema in early life. STUDY DESIGN: Subjects
      were included from the Copenhagen Prospective Study on Asthma in Childhood cohort
      of children born of mothers with asthma (N = 411). Severe asthma exacerbations
      and eczema were diagnosed by research unit physicians. Replication was sought in
      children from the Danish National Birth Cohort (N = 30 675). Asthma outcomes were
      hospitalization and use of inhaled corticosteroids. Eczema was defined by an
      algorithm developed from cases of clinically verified eczema. All children were
      followed to age 5 years in a cohort study design. RESULTS: The Copenhagen
      Prospective Study on Asthma in Childhood data showed increased risk of asthma
      exacerbation (hazard ratio 1.98 [95% CI 1.08-3.63]) if mothers had used
      antibiotics during third trimester. The Danish National Birth Cohort confirmed
      increased risk of asthma hospitalization (hazard ratio 1.17 [1.00-1.36]), and
      inhaled corticosteroids (1.18 [1.10-1.27]) in the children if mothers used
      antibiotics any time during pregnancy. In the subgroup of mothers using
      antibiotics for nonrespiratory infection, the children also had increased risk of
      asthma. CONCLUSION: We found increased risk of asthma associated with maternal
      antibiotic use in a clinical study of a birth cohort with increased risk of
      asthma and replicated this finding in an unselected national birth cohort, and in
      a subgroup using antibiotics for nonrespiratory infections. This supports a role
      for bacterial ecology in pre- or perinatal life for the development of asthma.

PMID- 23140882
TI  - Hypoplastic anemia in cartilage-hair hypoplasia-balancing between iron overload
      and chelation.
AB  - OBJECTIVE: To evaluate the severity of iron overload and the success of iron
      chelation therapy in patients with cartilage-hair hypoplasia (CHH) and
      hypoplastic anemia, with particular focus on adverse effects of iron chelators.
      STUDY DESIGN: Four of the 23 presently surviving Finnish patients with CHH under
      18 years of age are dependent on regular red blood cell transfusions. Their
      hospital records were reviewed for history of anemia and chelation therapy.
      Cumulative iron load from transfusions was calculated. Efficacy of the chelation
      therapy was evaluated biochemically and by liver iron content assessments.
      RESULTS: At the introduction of iron chelation, the patients had received on
      average 99 (37-151) transfusions; the mean cumulative iron overload was 4640 (800
      8200) mg, the annual iron accumulation rate 0.35 (0.25-0.41) mg/kg/d, and the
      mean plasma ferritin was 2896 (1217-6240) MUg/L. Liver iron content, determined
      by biopsy in 3 patients, was on average 20.0 (6.6-30.0) mg/g liver dry weight.
      All patients, except 1 with Hirschsprung disease, tolerated deferoxamine,
      deferiprone, and deferasirox therapy well, showing only mild adverse effects
      typical for the agents. Plasma ferritin levels and liver magnetic resonance
      imaging T2* of iron overload showed successful chelation. CONCLUSION: Iron
      chelation is well tolerated in patients with CHH, with possible exception of
      patients with Hirschsprung disease. Successful chelation will prepare for
      hematopoietic stem cell transplantation in patients with CHH with persistent
      transfusion dependency.

PMID- 23140883
TI  - Cerebral oxygenation, extraction, and autoregulation in very preterm infants who
      develop peri-intraventricular hemorrhage.
AB  - OBJECTIVE: To test the hypothesis that near-infrared spectroscopy (NIRS)
      determined patterns of regional cerebral oxygen saturation (rScO2), cerebral
      fractional tissue oxygen extraction (cFTOE), and autoregulatory ability can
      identify neonates at risk for developing peri-intraventricular hemorrhage (PIVH).
      STUDY DESIGN: This case-control study is a subanalysis of 30 neonates who
      developed PIVH >12 hours after admission as part of a lager prospective
      observational cohort study comprising 650 preterm neonates born at <=32 weeks'
      gestational age. PIVH was diagnosed by cranial ultrasound, performed at least
      once daily. Mean arterial blood pressure (MABP), NIRS-determined rScO2, cFTOE,
      and MABP-rScO2 correlation were monitored from birth to 72 hours of age. RESULTS:
      Infants with PIVH received more inotropic drugs before being diagnosed with PIVH.
      Significantly more infants with severe PIVH needed treatment for patent ductus
      arteriosus. The MABP-rScO2 correlation was >0.5 significantly more often before
      mild/moderate PIVH and after severe PIVH compared with controls. rScO2 was higher
      and cFTOE lower in infants before severe PIVH. CONCLUSION: NIRS-monitored rScO2
      and cFTOE suggest cerebral hyperperfusion in infants with severe PIVH. Moreover,
      MABP-rScO2 correlation indicates more blood pressure-passive brain perfusion in
      infants with PIVH. Continuous assessment of patterns of cerebral oxygenation and
      arterial blood pressure may identify those preterm infants at risk for severe
      PIVH and prompt consideration of preventive measures.

PMID- 23140884
TI  - Respiratory function in healthy late preterm infants delivered at 33-36 weeks of
      gestation.
AB  - OBJECTIVE: To compare pulmonary function testing including respiratory compliance
      (Crs) and time to peak tidal expiratory flow to expiratory time (TPTEF:TE) at
      term corrected age in healthy infants born at 33-36 weeks of gestation versus
      healthy infants delivered at term. STUDY DESIGN: We performed a prospective
      cohort study of late preterm infants born at 33-36 weeks without clinical
      respiratory disease (<12 hours of >0.21 fraction of inspired oxygen) and studied
      at term corrected age. The comparison group was term infants matched for race and
      sex to the preterm infants and studied within 72 hours of delivery. Crs was
      measured with the single breath occlusion technique. A minimum of 50 flow-volume
      loops were collected to estimate TPTEF:TE. RESULTS: Late preterm infants (n = 31;
      mean gestational age 34.1 weeks, birth weight 2150 g) and 31 term infants were
      studied at term corrected age. The late preterm infants had decreased Crs (1.14
      vs 1.32 mL/cm H(2)O/kg; P < .02) and decreased TPTEF:TE (0.308 vs 0.423; P < .01)
      when compared with the term infants. Late preterm infants also had an increased
      respiratory resistance (0.064 vs 0.043 cm H(2)O/mL/s; P < .01). CONCLUSIONS:
      Healthy late preterm infants (33-36 weeks of gestation) studied at term corrected
      age have altered pulmonary function when compared with healthy term infants.

PMID- 23140885
TI  - Synthesis and structure-activity relationships of tri-substituted thiazoles as
      RAGE antagonists for the treatment of Alzheimer's disease.
AB  - A series of thiazole derivatives were designed, and prepared to develop RAGE
      antagonist for the treatment of Alzheimer's disease (AD). SAR studies were
      performed to optimize inhibitory activity on Abeta-RAGE binding. SAR studies
      showed that introducing an amino group at part A was essential for inhibitory
      activity on Abeta-RAGE binding. Compounds selected from Abeta-RAGE binding
      screening displayed inhibitory activity on Abeta transport across BBB. They also
      showed inhibitory activity against Abeta-induced NF-kappaB activation. These
      results indicated that our derivatives had a potential as therapeutic agent for
      the treatment of AD.

PMID- 23140886
TI  - Synthesis and biological evaluation of 99mTc(CO)3(His-CB) as a tumor imaging
      agent.
AB  - The chlorambucil l-histidine conjugate was synthesized and radiolabeled with
      [(99m)Tc(CO)(3)](+) core to form the (99m)Tc(CO)(3)(His-CB) complex. The
      radiochemical purity of the complex was over 90%. It had good hydrophilicity and
      was stable at room temperature. The high initial tumor uptake with certain
      retention, fast clearance from background, good tumor/non-tumor ratios and
      satisfactory scintigraphic images highlighted the potential of (99m)Tc(CO)(3)(His
      CB) as a tumor imaging agent.

PMID- 23140887
TI  - Development of a dual functional luminescent sensor for zinc ion based on a
      peptidic architecture.
AB  - A synthetic peptide bearing a lanthanide complex, TbOTZ exhibits a decrease of
      chromophore fluorescence and a concomitant luminescence enhancement due to
      sensitized Tb(3+) upon Zn(2+) binding. Thus, TbOTZ can be a valuable tool for
      ratiometric sensing of Zn(2+) as well as for time-resolved fluorescence detection
      with a single molecule.

PMID- 23140888
TI  - Fake virus particles generated by fluorescence microscopy.
AB  - Many laboratories are actively studying the abundance and roles of viruses in
      natural ecosystems. In these studies, the presence and number of viral particles
      is usually determined using fluorescent dyes. However, DNA associated with
      membrane-derived vesicles (MVs), gene transfer agents (GTAs), or cell debris can
      produce fluorescent dots that can be confused with viral particles. We suspect
      that fluorescence counting can lead to overestimation of virus numbers and even
      suggest the presence of viruses when there are none. Future studies in
      environmental virology should acknowledge this point and consider how to bypass
      this problem. Besides trying to improve discrimination between virions and MVs,
      we suggest adopting less holistic approaches, focusing on the detection of known
      virus groups and the isolation of new viruses from a broader range of hosts.

PMID- 23140889
TI  - Ubiquitin-like proteins and their roles in archaea.
AB  - This review highlights the finding that ubiquitin-like (Ubl) proteins of archaea
      (termed SAMPs) function not only as sulfur carriers but also as protein
      modifiers. UbaA (an E1 ubiquitin-activating enzyme homolog of archaea) is
      required for the SAMPs to be covalently attached to proteins. The SAMPs and UbaA
      are also needed to form sulfur-containing biomolecules (e.g., thiolated tRNA and
      molybdenum cofactor). These findings provide a new perspective on how Ubl
      proteins can serve as both sulfur carriers and protein modifiers in the absence
      of canonical E2 ubiquitin conjugating or E3 ubiquitin ligase enzyme homologs.

PMID- 23140890
TI  - Pyocyanin effects on respiratory epithelium: relevance in Pseudomonas aeruginosa
      airway infections.
AB  - Pseudomonas aeruginosa (PA) uses several virulence factors to establish chronic
      respiratory infections in bronchiectasis, chronic obstructive pulmonary disease,
      and cystic fibrosis (CF) patients. One of its toxins, pyocyanin (PYO), is a redox
      active pigment that is required for full virulence in animal models and has been
      detected in patients' airway secretions. PYO promotes virulence by interfering
      with several cellular functions in host cells including electron transport,
      cellular respiration, energy metabolism, gene expression, and innate immune
      mechanisms. This review summarizes recent advances in PYO biology with special
      attention to current views on its role in human airway infections and on its
      interactions with the first line of our airway defense, the respiratory
      epithelium.

PMID- 23140893
TI  - Urban family cluster of spotted fever rickettsiosis linked to Rhipicephalus
      sanguineus infected with Rickettsia conorii subsp. caspia and Rickettsia
      massiliae.
AB  - Here, we report an epidemiological and entomological investigation of a cluster
      of cases of spotted fever group (SFG) rickettsiosis occurring in southern France.
      A family of 3 (husband, wife, and their son) presented with symptoms compatible
      with SFG rickettsiosis. For 2 patients, serum samples presented increased levels
      of IgM and IgG for SFG Rickettsia. The patients' home was investigated, and
      Rhipicephalus sanguineus ticks were collected from the floor from behind the
      furniture. Of 22 ticks collected, 20 tested positive for Rickettsia. As Rh.
      sanguineus serves as a vector for both Rickettsia conorii and Ri. massiliae in
      southern France, all Rh. sanguineus isolates were tested by real-time PCR and
      conventional PCR to detect the 2 species. Nine ticks tested positive for Ri.
      conorii subsp. caspia (marking the first documentation of this subspecies in
      France), 7 tested positive for Ri. massiliae, and 4 tested positive for both
      rickettsiae. This study is the first report of coinfection of Rh. sanguineus
      ticks with Ri. conorii and Ri. massiliae in southern France.

PMID- 23140892
TI  - Genetic characterization of Candidatus Rickettsia vini, a new rickettsia
      amplified in ticks from La Rioja, Spain.
AB  - A total of 222 ticks removed from birds in La Rioja (Spain) were screened for
      spotted fever group rickettsia species using ompA PCR assays. Rickettsia
      monacensis (n=1) and R. sibirica (n=1) were detected. Apart from that, 27 out of
      29 Ixodes spp. DNA extracts that tested positive for ompA did not match with any
      validated spotted fever group rickettsia. Multilocus sequence typing for 16S
      rRNA, gltA, ompB, sca4, and 17-kDa antigen genes was performed, and R.
      heilongjiangensis was found to be the nearest validly published spotted fever
      group rickettsia. Based on genetic criteria agreed by experts, this genotype can
      be classified as a new Candidatus Rickettsia sp. and was named Candidatus
      Rickettsia vini.

PMID- 23140891
TI  - A voxel-based morphometry (VBM) analysis of regional grey and white matter volume
      abnormalities within the speech production network of children who stutter.
AB  - It is well documented that neuroanatomical differences exist between adults who
      stutter and their fluently speaking peers. Specifically, adults who stutter have
      been found to have more grey matter volume (GMV) in speech relevant regions
      including inferior frontal gyrus, insula and superior temporal gyrus (Beal et
      al., 2007; Song et al., 2007). Despite stuttering having its onset in childhood
      only one study has investigated the neuroanatomical differences between children
      who do and do not stutter. Chang et al. (2008) reported children who stutter had
      less GMV in the bilateral inferior frontal gyri and middle temporal gyrus
      relative to fluently speaking children. Thus it appears that children who stutter
      present with unique neuroanatomical abnormalities as compared to those of adults
      who stutter. In order to better understand the neuroanatomical correlates of
      stuttering earlier in its development, near the time of onset, we used voxel
      based morphometry to examine volumetric differences between 11 children who
      stutter and 11 fluent children. Children who stutter had less GMV in the
      bilateral inferior frontal gyri and left putamen but more GMV in right Rolandic
      operculum and superior temporal gyrus relative to fluent children. Children who
      stutter also had less white matter volume bilaterally in the forceps minor of the
      corpus callosum. We discuss our findings of widespread anatomic abnormalities
      throughout the cortical network for speech motor control within the context of
      the speech motor skill limitations identified in people who stutter (Namasivayam
      and van Lieshout, 2008; Smits-Bandstra et al., 2006). 

PMID- 23140895
TI  - Prevalence of antibodies against Rickettsia conorii, Babesia canis, Ehrlichia
      canis, and Anaplasma phagocytophilum antigens in dogs from the Stretto di Messina
      area (Italy).
AB  - The aims of this study were to determine the seroprevalence for Rickettsia
      conorii, Ehrlichia canis, Anaplasma phagocytophilum, and Babesia canis in outdoor
      kennelled dogs (n=249) from the Stretto di Messina (Italy) and to compare
      seroprevalence in 2 public shelters and 4 privately-owned kennels where different
      tick-preventive measures were implemented in order to focus on the specific
      sanitary risk posed by public shelters in southern Italy for tick-borne
      pathogens. R. conorii (72%) and B. canis (70%) were the most prevalent infections
      when compared to E. canis (46%) and A. phagocytophilum (38%). Seroprevalence for
      R. conorii, E. canis, and A. phagocytophilum was significantly higher in public
      shelters than in private kennels. However, B. canis seropositivity was similar in
      both types of kennels. In addition, in private kennels where a regular ectocide
      treatment was carried out by means of spot-on devices, dogs did not present E.
      canis and A. phagocytophilum antibodies. One hundred fifty-one dogs out of 249
      (61%) were seropositive to more than one pathogen with R. conorii and B. canis
      the most common ones. Coinfections were more frequently found in public-shelter
      dogs. This study demonstrated high seroprevalences against R. conorii, B. canis,
      E. canis, and A. phagocytophilum in kennelled dogs from both coastal sites of the
      Stretto di Messina and the importance of regular tick-bite prevention by means of
      individual spot-on devices.

PMID- 23140894
TI  - Tick cell culture isolation and growth of Rickettsia raoultii from Dutch
      Dermacentor reticulatus ticks.
AB  - Tick cell lines play an important role in research on ticks and tick-borne
      pathogenic and symbiotic microorganisms. In an attempt to derive continuous
      Dermacentor reticulatus cell lines, embryo-derived primary cell cultures were set
      up from eggs laid by field ticks originally collected as unfed adults in The
      Netherlands and maintained for up to 16 months. After several months, it became
      evident that cells in the primary cultures were infected with a Rickettsia-like
      intracellular organism. Supernatant medium containing some D. reticulatus cells
      was inoculated into cultures of 2 Rhipicephalus (Boophilus) microplus cell lines,
      BME/CTVM2 and BME/CTVM23, where abundant growth of the bacteria occurred
      intracellularly on transfer to both cell lines. Bacterial growth was monitored by
      light (live, inverted microscope, Giemsa-stained cytocentrifuge smears) and
      transmission electron microscopy revealing heavy infection with typical
      intracytoplasmic Rickettsia-like bacteria, not present in uninfected cultures.
      DNA was extracted from bacteria-infected and uninfected control cultures, and
      primers specific for Rickettsia 16S rRNA, ompB, and sca4 genes were used to
      generate PCR products that were subsequently sequenced. D. reticulatus primary
      cultures and both infected tick cell lines were positive for all 3 Rickettsia
      genes. Sequencing of PCR products revealed 99-100% identity with published
      Rickettsia raoultii sequences. The R. raoultii also grew abundantly in the D.
      nitens cell line ANE58, poorly in the D. albipictus cell line DALBE3, and not at
      all in the D. andersoni cell line DAE15. In conclusion, primary tick cell
      cultures and cell lines are useful systems for isolation and propagation of
      fastidious tick-borne microorganisms. In vitro isolation of R. raoultii from
      Dutch D. reticulatus confirms previous PCR-based detection in field ticks, and
      presence of the bacteria in the tick eggs used to initiate the primary cultures
      confirms that transovarial transmission of this Rickettsia occurs.

PMID- 23140896
TI  - First detection of Ehrlichia canis in Rhipicephalus bursa ticks in Sardinia,
      Italy.
AB  - Canine monocytic ehrlichiosis is a common and widespread disease. This disease is
      present in Sardinia year-round because the temperate weather on the island
      permits the survival of many types of tick vectors. A total of 35 ticks was
      collected from goats in south-eastern Sardinia, Italy, and tested for Ehrlichia
      DNA using polymerase chain reaction and DNA sequencing. This study provides the
      first evidence of the presence of Ehrlichia canis in Rhipicephalus bursa ticks.
      The data presented here increase our knowledge of tick-borne diseases in Sardinia
      and provide a useful contribution toward understanding their epidemiology. The
      role of R. bursa in the life cycle and transmission of E. canis needs however
      further investigation.

PMID- 23140897
TI  - Rickettsia slovaca from Dermacentor marginatus ticks in Sardinia, Italy.
AB  - Nineteen ticks belonging to the species Dermacentor marginatus, Rhipicephalus
      bursa, and Haemaphysalis sulcata were collected from wild animals (wild boar,
      deer, and mouflon) in south-western Sardinia, Italy. Five D. marginatus ticks
      from wild boar were PCR-positive when analyzed using gltA-specific and ompA
      specific primers, leading to the identification and first isolation in cell
      culture of Rickettsia slovaca, the causative agent of tick-borne lymphadenopathy
      (TIBOLA), on the island of Sardinia. This study confirms the detection of a new
      tick-borne rickettsia that can be added to the others already known to be present
      in Sardinia (Rickettsia aeschlimannii, R. massiliae, and Candidatus Rickettsia
      barbariae). These data increase our knowledge of tick-borne rickettsioses in
      Sardinia and, more generally, in the Mediterranean basin.

PMID- 23140898
TI  - Candidatus Rickettsia hoogstraalii in Ethiopian Argas persicus ticks.
AB  - Ethiopian soft ticks Argas persicus, hard ticks including both Amblyomma
      variegatum and Rhipicephalus (Boophilus) spp., and fleas were collected from
      livestock, traditional human dwellings, and cracks and crevices of trees. They
      were assessed in pools for the presence of Rickettsia using PCR-based methods.
      The extracted tick DNA was subjected to molecular screening for Rickettsia, which
      revealed 50.5% of the pooled samples to be positive for Rickettsia spp. These
      were then subjected to multi-gene analysis using both outer surface proteins and
      housekeeping genes with proven discriminatory potential. Sequencing of the
      citrate synthase and outer membrane genes clearly led to the identification of
      three distinct rickettsial species, Candidatus Rickettsia hoogstraalii in Argas
      persicus ticks; R. africae in hard tick pools, and R. felis in fleas.
      Furthermore, we demonstrated the presence of the plasmid-borne small heat-shock
      protein gene hsp2 in DNA from A. persicus ticks suggesting that Candidatus R.
      hoogstraalii carried by these ticks possess a plasmid. Unlike chromosomal gene
      sequences, the hsp2 gene failed to cluster with Candidatus R. hoogstraalii,
      instead falling into an isolated separate clade, suggesting a different origin
      for the plasmid.

PMID- 23140899
TI  - Controlled release of HNO from chemical donors for biological applications.
AB  - Nitroxyl (HNO) is a small molecule with various pharmacological effects,
      including cardioprotective action. It is thought to serve as a modulator of
      various biochemical pathways. But, it is difficult to apply HNO directly for
      biological experiments or therapeutic treatment because it is highly reactive,
      readily dimerizing or reacting with biological targets under ambient conditions.
      Therefore, HNO donor molecules that release HNO under physiological conditions,
      especially those that allow precisely controllable release, would be useful to
      study the activities of HNO at the cellular level. This short review focuses on
      recently developed photocontrollable HNO-releasing compounds, which are expected
      to be suitable for achieving site-specific and temporally controlled HNO release
      in biomedical investigations. An illustrative application for the study of HNO
      mediated upregulation of calcitonin gene-related peptide (CGRP) in A549 cells is
      described.

PMID- 23140900
TI  - A singular value decomposition approach for kinetic analysis of reactions of HNO
      with myoglobin.
AB  - The reactions of several horse heart myoglobin species with nitrosyl hydride,
      HNO, derived from Angeli's salt (AS) and Piloty's acid (PA) have been followed by
      UV-visible, (1)H NMR and EPR spectroscopies. Spectral analysis of myoglobin
      derived speciation during the reactions was obtained by using singular value
      decomposition methods combined with a global analysis to obtain the rate
      constants of complex sequential reactions. The analysis also provided spectra for
      the derived absorbers, which allowed self-consistent calibration to the spectra
      of known myoglobin species. Using this method, the determined rate for trapping
      of HNO by metmyoglobin, which produces NO-myoglobin, is found to be 2.7 * 10(5)M(
      1)s(-1) at pH7.0 and 1.1 * 10(5)M(-1)s(-1) at pH9.4. The reaction of
      deoxymyoglobin with HNO generates the adduct HNO-myoglobin directly, but is
      followed by a secondary reaction of that product with HNO yielding NO-myoglobin;
      the determined bimolecular rate constants for these reactions are 3.7 * 10(5)M(
      1)s(-1) and 1.67 * 10(4)M(-1)s(-1) respectively, and are independent of pH. The
      derived spectrum for HNO-myoglobin is characterized by a Soret absorbance maximum
      at 423 nm with an extinction coefficient of 1.66 * 10(5)M(-1)cm(-1). The rate
      constant for unimolecular loss of HNO from HNO-myoglobin was determined by
      competitive trapping with CO at 8.9 * 10(-5)s(-1), which gives the thermodynamic
      binding affinity of HNO to deoxymyoglobin as 4.2 * 10(9)M(-1). These results
      suggest that the formation of HNO-ferrous heme protein adducts represents an
      important consideration in the biological action of HNO-releasing drugs.

PMID- 23140901
TI  - [Beliefs, attitudes and influence of the media in Spanish health care workers
      during the A (H1N1) 2009 flu pandemic].
AB  - INTRODUCTION: The aim of this article is to report, from their own perspective,
      the attitudes and believes towards vaccination, with special emphasis on the
      influence of sources of information to make the decision to get vaccinated, of
      health care workers (HCWs), considered as a specific risk group for immunization
      strategy against A (H1N1) influenza. METHODS: Cross-sectional observational study
      focused on active health workers in the province of Alicante. Made by face to
      face questionnaires to a stratified random sample based on occupational
      categories in hospitals and health care centres. RESULTS: The sources of
      information differ between subgroups; physicians used journals and/or
      conferences, nurses obtained information through the Ministry of Health and other
      nurses, and the remaining workers opted for television and/or the family
      physician. Of the three studied groups, physicians felt minor concern about the
      influenza A (H1N1) pandemic (59.4%), had the most confidence in the vaccine
      (42.3%), were the ones who recommended the vaccine the most (44.4%), who best
      followed the recommendations to avoid infection (93%), and were the most
      vaccinated (18.3%). Around three-quarters (75.5%) of the HCWs assessed the
      provided information as fair, poor or very poor. All HCWs admitted that a social
      alarm was created. DISCUSSION: The success of future immunization campaigns
      against influenza in HCWs could increase if information activities were designed
      to focus on each subgroup of HCWs, by adapting the strategy and improving the
      quality of information.

PMID- 23140902
TI  - Are marine environmental pollutants influencing global patterns of human disease?
AB  - Thousands of toxic chemicals, many of which pollute marine ecosystems,
      potentially cause diseases, but building a consensus view of the significance of
      human body burdens of environmental chemicals is proving difficult. Causative
      mechanisms are often lacking. Older members of the population, of which there are
      increasing numbers worldwide, accumulate higher body burdens than the young, and
      may be especially at risk. It also remains unclear when crucially sensitive
      periods for chemical exposures occur across the life course. Very early exposures
      may lead to diseases much later on. The current lack of robust science upon which
      to base high quality expert advice is hampering effective policymaking that leads
      to further reductions in marine pollution, greater protection of marine life and
      lowering of risks to human health.

PMID- 23140903
TI  - Evidence-based medicine in India.

PMID- 23140904
TI  - Unaffected control of distractor interference in schizophrenia: a meta-analysis
      of incompatibility slowing in flanker tasks.
AB  - In schizophrenia research executive functions have been frequently reported to be
      impaired on a global level, largely ignoring the fact that the term executive
      functions refers to a collection of cognitive functions, which may be affected
      independently of each other. In the present meta-analysis we were able to show
      that an aspect of interference control, the ability to resist to distracting
      information, is not substantially affected in schizophrenia. Summarizing the
      results of 21 studies using a flanker task, we did not find an increased
      incompatibility slowing (relative to a compatible flanker condition). The mean
      effect size, integrating the data of 1029 schizophrenia and 848 controls, was
      with M(g) = 0.037 (95% confidence interval: -0.05 to 0.13) small and the test
      power was with 1-beta = 0.991 sufficiently high to exclude even small population
      effects. A similar result was obtained when analyzing the incompatibility slowing
      relative to a neutral flanker condition (8 studies, M(g) = -0.032, 95% confidence
      interval: -0.16 to 0.09). In not being substantially affected in schizophrenia,
      the ability to resist distractor interference could serve as "scaffold function",
      which used by cognitive remediation programs, would allow to build up general
      functions, such as vigilance and attention, before the affected executive
      abilities would be addressed.

PMID- 23140905
TI  - Improved femoral component rotation in TKA using patient-specific
      instrumentation.
AB  - BACKGROUND: Patient-specific instrumentation (PSI) was introduced in an attempt
      to reduce positional outliers of components in total knee arthroplasty (TKA). It
      was hypothesized that PSI could help with the positioning of femoral components
      in optimal rotational alignment. METHODS: A magnetic resonance imaging (MRI)
      analysis of 94 patients following TKA was conducted. Of these, 46 operations were
      performed using PSI and 48 using conventional instrumentation. The rotation of
      the femoral components was determined in the MRI and deviations>3 degrees  were
      considered outliers. Data were analyzed for positional outliers, observer
      reliability, and a variance comparison between implant groups. RESULTS: There was
      excellent inter- and intraobserver reliability with low standard deviations for
      the determination of femoral component rotation. There were significantly more
      outliers in the conventional (22.9%) group than in the PSI group (2.2%, p=0.003).
      CONCLUSION: In this setup, PSI was effective in significantly reducing outliers
      of optimal rotational femoral component alignment during TKA.

PMID- 23140906
TI  - Component rotational alignment in unexplained painful primary total knee
      arthroplasty.
AB  - BACKGROUND: Rotational malalignment of the components in total knee arthroplasty
      (TKA) can be a factor in poor outcomes but has yet to be defined. This study
      compares the rotational alignment of components in a cohort of 56 patients with
      unexplained pain following total knee arthroplasty with a matched control cohort
      of 56 patients with cemented Nex Gen Legacy posterior stabilised (LPS) flex fixed
      bearing TKA between March 2006 and May 2010. The aim of the study was to define
      an acceptable limit of rotation in total knee replacement. METHODS: Rotational
      alignment was calculated using the Berger protocol with post operative
      computerised tomography scanning. The alignment parameters measured were tibial
      and femoral component rotations and the combined component rotations and the
      component rotational mismatch. RESULTS: The two cohorts were demographically
      matched. Excessive internal rotation of the components was defined using the
      tenth percentile of rotations in the control cohort. Values of excessive internal
      rotation were 5.8 degrees  of the tibial component, 3.9 degrees  of the femoral
      component, 8.7 degrees  of combined rotation and 5.6 degrees  of the component
      mismatch. No significant difference was identified in excessive external rotation
      in any of the parameters. A significant difference in the mean rotations between
      the two cohorts was identified with internal rotation of the components in the
      painful cohort and external rotation on the control cohort. CONCLUSIONS: We
      identified internal rotation malalignment of the tibial (p=0.0003) and femoral
      (p=0.014) components individually as well as the combined component rotation
      (p=0.0003) and component rotation mismatch (p=0.0001) to be a factor in pain
      following TKA. External rotation of any of the component parameters was not
      identified to be a factor in painful TKA. This study adds to the understanding of
      rotational alignment in TKA and suggests limits of internal rotation alignment
      associated with painful Nex Gen Legacy posterior stabilised (LPS) flex fixed
      bearing TKA. LEVEL OF EVIDENCE: Level III.

PMID- 23140907
TI  - Utilization and costs of glucose lowering therapies following health technology
      assessment for the new reimbursement scheme in Sweden.
AB  - OBJECTIVES: A new reimbursement scheme (RS) for glucose lowering therapies (GLT)
      was implemented in Sweden on March 1, 2010. Products on the market were retained,
      restricted, excluded or excluded for new courses in the new RS. The aim of this
      study was to compare utilization and costs of GLT for type 2 diabetes Mellitus
      (T2DM) before and after the implementation of the changed RS. METHODS: This was a
      quasi-experimental study using data on dispensed GLT and costs from a database on
      dispensed individual based prescriptions in Sweden. Segmented regression analyses
      were used to assess utilization and costs. RESULTS: Following the changed
      reimbursement status, there was an accelerated increasing trend in number of
      patients treated with restricted (P=0.0007) or retained (P=0.0021) insulins, as
      well as in costs for insulin based GLT (P=0.0014). No impact was detected in the
      total number of patients treated with oral GLT, but a slightly negative trend in
      total costs for oral GLT was detected following the intervention (P=0.0177).
      CONCLUSIONS: The new reimbursement scheme had a minor impact on utilization and
      costs of oral GLT. Despite restricted reimbursement for patients with T2DM, the
      utilization of insulin based GLT and related costs increased faster following the
      intervention.

PMID- 23140908
TI  - Predictors of severe pain in a cohort of 5271 individuals with self-reported
      neuropathic pain.
AB  - The influence of pain descriptors and mechanical hypersensitivity on pain
      severity in neuropathic pain has not been well researched and is poorly
      understood. The aim of this study was to determine the relationship between pain
      severity and other factors describing chronic neuropathic pain in a large cohort
      of patients with self-reported neuropathic pain potentially recruited as subjects
      for a Phase IIa study. A questionnaire specific to the study parameters covering
      demographics and pain characteristics was sent to potential participants.
      Overall, 9185 questionnaires were returned from potential subjects who self
      reported neuropathic pain. Adjusted odds ratios with 95% confidence intervals
      were used as a measure of association. These were estimated by unconditional
      logistic regression. Pain descriptors in the questionnaire were: burning,
      shooting, shocking, and aching. The presence of self-reported allodynia and
      hyperalgesia was strongly indicative of both moderate and severe pain, with a
      significant interaction of both factors in moderate and severe pain. Having 3 or
      4 pain descriptors was also strongly indicative of both moderate and severe pain.
      Female gender, age, and history of serious mental disorders were found to be
      weaker indicators of both moderate and severe pain. Given the large and varied
      population with many neuropathic pain diagnoses in the study, the findings are
      not likely to be merely chance, but are likely to reflect important relationships
      between pain severity and other factors in those who suffer from chronic
      neuropathic pain.

PMID- 23140909
TI  - Quantitative cerebral blood flow mapping and functional connectivity of
      postherpetic neuralgia pain: a perfusion fMRI study.
AB  - This article investigates the effects of postherpetic neuralgia (PHN) on resting
      state brain activity utilizing arterial spin labeling (ASL) techniques. Features
      of static and dynamic cerebral blood flow (CBF) were analyzed to reflect the
      specific brain response to PHN pain. Eleven consecutive patients suffering from
      PHN and 11 age- and gender-matched control subjects underwent perfusion
      functional magnetic resonance imaging brain scanning during the resting state.
      Group comparison was conducted to detect the regions with significant changes of
      CBF in PHN patients. Then we chose those regions that were highly correlated with
      the self-reported pain intensity as "seeds" to calculate the functional
      connectivity of both groups. Absolute CBF values of these regions were also
      compared across PHN patients and control subjects. Significant increases in CBF
      of the patient group were observed in left striatum, right thalamus, left primary
      somatosensory cortex (S1), left insula, left amygdala, left primary somatomotor
      cortex, and left inferior parietal lobule. Significant decreases in CBF were
      mainly located in the frontal cortex. Regional CBF in the left caudate, left
      insula, left S1, and right thalamus was highly correlated with the pain
      intensity, and further comparison showed that the regional CBF in these regions
      is significantly higher in PHN groups. Functional connectivity results
      demonstrated that the reward circuitry involved in striatum, prefrontal cortex,
      amygdala, and parahippocampal gyrus and the circuitry among striatum, thalamus,
      and insula were highly correlated with each element in PHN patients. In addition,
      noninvasive brain perfusion imaging at rest may provide novel insights into the
      central mechanisms underlying PHN pain.

PMID- 23140910
TI  - Impact of differences in glucose tolerance on the prevalence of a negative
      insulinogenic index.
AB  - OBJECTIVE: To determine the prevalence of a negative insulinogenic index (change
      in plasma insulin/change in plasma glucose from 0 to 30 min) from an oral glucose
      tolerance test according to glucose tolerance category. MATERIALS AND METHODS:
      Data from the San Antonio Heart Study (n=2494), Japanese American Community
      Diabetes Study (JACDS; n=594) and Genetics of NIDDM Study (n=1519) were examined.
      Glucose tolerance was defined by ADA criteria. RESULTS: In the combined cohort,
      the prevalence of a negative insulinogenic index was significantly higher in
      diabetes 20/616 (3.2%) compared to normal glucose tolerance 43/2667 (1.6%)
      (p<0.05). Longitudinally, in the JACDS cohort, the prevalence did not change from
      baseline (3/594; 0.5%) to 5 (4/505; 0.7%) and 10 years (8/426; 1.9%) (p=0.9) and
      no subject had a repeat negative insulinogenic index. CONCLUSIONS: A negative
      insulinogenic index occurs at a low prevalence across glucose tolerance
      categories although more often in diabetes, but without recurrence over time.

PMID- 23140911
TI  - Antioxidant, anti-diabetic and renal protective properties of Stevia rebaudiana.
AB  - BACKGROUND: Stevia rebaudiana Bertoni has been used for the treatment of diabetes
      in, for example, Brazil, although a positive effect on antidiabetic and its
      complications has not been unequivocally demonstrated. This herb also has
      numerous therapeutic properties which have been proven safe and effective over
      hundreds of years. Streptozotocin is a potential source of oxidative stress that
      induces genotoxicity. OBJECTIVE: We studied the effects of stevia leaves and its
      extracted polyphenols and fiber on streptozotocin induced diabetic rats. We
      hypothesize that supplementation of polyphenols extract from stevia to the diet
      causes a reduction in diabetes and its complications. DESIGN/METHODS: Eighty
      Wistar rats were randomly divided into 8 groups; a standard control diet was
      supplemented with either stevia whole leaves powder (4.0%) or polyphenols or
      fiber extracted from stevia separately and fed for one month. Streptozotocin (60
      mg/kg body weight, i.p) was injected to the diabetic groups on the 31st day.
      Several indices were analyzed to assess the modulation of the streptozotocin
      induced oxidative stress, toxicity and blood glucose levels by stevia. RESULTS:
      The results showed a reduction of blood glucose, ALT and AST, and increment of
      insulin level in the stevia whole leaves powder and extracted polyphenols fed
      rats compared to control diabetic group. Its feeding also reduced the MDA
      concentration in liver and improved its antioxidant status through antioxidant
      enzymes. Glucose tolerance and insulin sensitivity were improved by their
      feeding. Streptozotocin was also found to induce kidney damage as evidenced by
      decreased glomerular filtration rate; this change was however alleviated in the
      stevia leaves and extracted polyphenol fed groups. CONCLUSION: The results
      suggested that stevia leaves do have a significant role in alleviating liver and
      kidney damage in the STZ-diabetic rats besides its hypoglycemic effect. It might
      be adequate to conclude that stevia leaves could protect rats against
      streptozotocin induced diabetes, reduce the risk of oxidative stress and
      ameliorate liver and kidney damage.

PMID- 23140913
TI  - Assessment of nasal obstruction: correlation between subjective and objective
      techniques.
AB  - BACKGROUND: Nasal sensation of airflow describes the perception of the passage of
      air through the nose. Nasal obstruction can be assessed using subjective
      techniques (symptom scores and visual analogue scales [VAS]) and objective
      techniques (anterior rhinomanometry [RMN], acoustic rhinometry [AR], and peak
      nasal inspiratory flow [PNIF]). Few studies have evaluated the correlation
      between these techniques. OBJECTIVE: The primary objective of our study was to
      determine the degree of correlation between subjective and objective techniques
      to assess nasal obstruction. MATERIALS AND METHODS: Nasal obstruction was
      assessed using a symptom score, VAS, RMN, AR (minimal cross-sectional area [MCSA]
      and volume), and PNIF in 184 volunteer physicians. Spearman's rho was recorded.
      Correlations were considered weak if r <= 0.4, moderate if 0.4 < r < 0.8, and
      strong if r > 0.8. RESULTS: Mean (SD) age was 37.1 (6.9) years (range, 25-56
      years); 61% were women. We found a strong correlation (r > 0.8; p = 0.001)
      between the different parameters of RMN and a moderate correlation between
      symptom score and VAS (r = 0.686; p = 0.001) and between MCSA and RMN
      (resistance) (r = 0.496; p = 0.001) and PNIF (r = 0.459; p = 0.001). The
      correlations were weak or non-significant for the remaining comparisons.
      CONCLUSION: Nasal obstruction can be assessed using subjective and objective
      approaches. The correlations between objective techniques were moderate to
      strong. In addition, between subjective techniques we reported a moderate
      correlation. Finally, the correlations between the subjective and objective
      techniques were weak and absent. These findings suggest that each of the
      techniques assesses different aspects of nasal obstruction, thus making them
      complementary.

PMID- 23140914
TI  - Simulation of cumulative damage associated with long term cyclic loading using a
      multi-level strain accommodating loading protocol.
AB  - OBJECTIVE: To assess step by step the associated cumulative damage introduced in
      zirconia veneered restorations after long term cyclic loading using a new multi
      level strain accommodating loading protocol. METHODS: 40 zirconia veneered crowns
      received thermal and cyclic loading (3.5 million cycles at maximum load of 25 kg
      representing 70% of the critical load of the veneer ceramic). The used loading
      protocol allowed for reproduction of the combined damping action of the
      periodontal ligament, food substance, jaw deformation, and free movement of the
      mandibular joint. Speed of load application and release was obtained from the
      chewing cycle of adult patients. Principles of fractographic analysis were used
      to study the behavior and origin of critical crack and associated structural
      damage. RESULTS: The multi-level strain damping effect prevented generation of
      cone cracks and contact damage under the loading indenter commonly associated
      with fracture strength tests. 29 specimens (73%) survived 3.5 million cycles
      without fracture, 9 specimens (22%) demonstrated cohesive fracture of the veneer
      ceramic and limited axial fracture of the framework was observed in two specimens
      (5%). Of all fractured specimens, 2 restorations (5%) failed after 500,000 cycles
      while the rest survived at least 3 million cycles before fracture was observed.
      Fractographic analysis revealed initial wear and abrasion below the loading area,
      subsurface micro-cracking of the glass matrix followed by slow crack growth that
      traveled in a stepping pattern till deflection at zirconia veneer interface.
      SIGNIFICANCE: Cyclic loading using multi-level strain accommodating model can
      reproduce clinical failure. With exception to manufacturing errors, zirconia
      veneered restoration survived a simulated 7-year service time without fracture.

PMID- 23140915
TI  - Correlating in vitro scratch test with in vivo contact free occlusal area wear of
      contemporary dental composites.
AB  - OBJECTIVES: The aims of this study are to determine the extent to which the
      ranking order for clinical Contact-Free-Occlusal-Area (CFOA) wear performance of
      composites correlates with the ranking based on in vitro scratch hardness, and to
      analyze the extent to which the microstructure influences the overall trend.
      MATERIALS AND METHODS: The patient data and CFOA wear measurements of 16 Tetric
      C, 17 Tetric-EC, 16 Gradia-DP, 18 Filtek Supreme, 19 Z100 restorations in 31
      subjects (8 males, 23 females) of two randomized clinical trials were fitted in a
      mixed-effect model. The in vivo performance of the restoratives was summarized by
      ranking the estimated material-related coefficients in the model. Scratch tests
      on two specimens per composite were run at a constant speed of 0.05 mm/s under
      indenter with normal loads of 15, 25, and 35 mN. Scratch width, depth and
      hardness calculated by imaging the scratch tracks were summarized in a model, the
      material-related coefficients were ranked and correlated with that of in vivo
      ranking order. RESULTS: The best in vivo model included as significant factors
      (p<0.0001) the variables material, time/month, cavity type, and jaw type. The
      CFOA wear ranking order - Filtek Supreme, Z100>Tetric-C, Tetric-EC>Gradia-DP
      correlated closely (R(2)=0.991) with the order of scratch hardness - Z100>Filtek
      Supreme>Tetric-C, Tetric-EC>Gradia-DP. SIGNIFICANCE: Scratch tests could roughly
      categorize a new material as to whether it will probably exhibit a high or low in
      vitro scratch resistance and/or clinical CFOA wear rate.

PMID- 23140917
TI  - [1st National Conference 'Unity and Value of Italian Surgery' ... with the lights
      off].

PMID- 23140916
TI  - Novel calcium phosphate nanocomposite with caries-inhibition in a human in situ
      model.
AB  - OBJECTIVES: Secondary caries at the restoration margins remains the main reason
      for failure. Although calcium phosphate (CaP) composites are promising for caries
      inhibition, there has been no report of CaP composite to inhibit caries in situ.
      The objectives of this study were to investigate the caries-inhibition effect of
      nanocomposite containing nanoparticles of amorphous calcium phosphate (NACP) in a
      human in situ model for the first time, and to determine colony-forming units
      (CFU) and Ca and P ion concentrations of biofilms on the composite restorations.
      METHODS: NACP with a mean particle size of 116 nm were synthesized via a spray
      drying technique. Two composites were fabricated: NACP nanocomposite, and control
      composite filled with glass particles. Twenty-five volunteers wore palatal
      devices containing bovine enamel slabs with cavities restored with NACP or
      control composite. After 14 days, the adherent biofilms were collected for
      analyses. Transverse microradiography determined the enamel mineral profiles at
      the margins, and the enamel mineral loss DeltaZ was measured. RESULTS: NACP
      nanocomposite released Ca and P ions and the release significantly increased at
      cariogenic low pH (p<0.05). Biofilms on NACP nanocomposite contained higher Ca
      (p=0.007) and P ions (p=0.005) than those of control (n=25). There was no
      significant difference in biofilm CFU between the two composites (p>0.1).
      Microradiographs showed typical subsurface lesions in enamel next to control
      composite, but much less lesion around NACP nanocomposite. Enamel mineral loss
      DeltaZ (mean+/-sd; n=25) around NACP nanocomposite was 13.8+/-9.3 MUm, much less
      than 33.5+/-19.0 MUm of the control (p=0.001). SIGNIFICANCE: Novel NACP
      nanocomposite substantially reduced caries formation in a human in situ model for
      the first time. Enamel mineral loss at the margins around NACP nanocomposite was
      less than half of the mineral loss around control composite. Therefore, the Ca
      and P ion-releasing NACP nanocomposite is promising for caries-inhibiting
      restorations.

PMID- 23140918
TI  - Multiple endocrine neoplasia, the old and the new: a mini review.
AB  - Multiple endocrine neoplasia syndromes have since been classified as types 1 and
      2, each with specific phenotypic patterns. MEN1 is usually associated with
      pituitary, parathyroid and paraneoplastic neuroendocrine tumours. The hallmark of
      MEN2 is a very high lifetime risk of developing medullary thyroid carcinoma (MTC)
      more than 95% in untreated patients. Three clinical subtypesdMEN2A, MEN2B, and
      familial MTC (FMTC) have been defined based on the risk of pheochromocytoma,
      hyperparathyroidism, and the presence or absence of characteristic physical
      features). MEN2 occurs as a result of germline activating missense mutations of
      the RET (REarranged during Transfection) proto-oncogene. MEN2-associated
      mutations are almost always located in exons 10, 11, or 13 through 16. Strong
      genotype-phenotype correlations exist with respect to clinical subtype, age at
      onset, and aggressiveness of MTC in MEN2. These are used to determine the age at
      which prophylactic thyroidectomy should occur and whether screening for
      pheochromocytoma or hyperparathyroidism is necessary. Specific RET mutations can
      also impact management in patients presenting with apparently sporadic MTC.
      Therefore, genetic testing should be performed before surgical intervention in
      all patients diagnosed with MTC. Recently, Pellegata et al. have reported that
      germline mutations in CDKN1B can predispose to the development of multiple
      endocrine tumours in both rats and humans and this new MEN syndrome is named MENX
      and MEN4, respectively. CDKN1B. A recent report showed that in sporadic MTC,
      CDKN1B V109G polymorphism correlates with a more favorable disease progression
      than the wild-type allele and might be considered a new promising prognostic
      marker. New insights on MEN syndrome pathogenesis and related inherited endocrine
      disorders are of particular interest for an adequate surgical and therapeutic
      approach.

PMID- 23140919
TI  - Role of pre and post-operative oral calcium and vitamin D supplements in
      prevention of hypocalcemia after total thyroidectomy.
AB  - AIM: to evaluate the role of pre and post-operative oral calcium and vitamin D
      supplements in prevention of hypocalcemia after total thyroidectomy. PATIENTS AND
      METHODS: 50 consecutive patients, undergoing total thyroidectomy, were enrolled.
      Oral calcium and vitamin D were administered in the pre and post-operative time.
      The data concerning symptomatic and laboratoristic hypocalcemia were collected.
      RESULTS: Incidence of symptomatic hypocalcemia was very low (6%); incidence of
      laboratoristic hypocalcemia was 10%. No permanent hypocalcemia developed.
      CONCLUSIONS: Implementing oral calcium and vitamin D both before and after total
      thyroidectomy can reduce the incidence of hypocalcemia related to surgery.

PMID- 23140920
TI  - Long-term outcomes following "presumed" total parathyroidectomy for secondary
      hyperparathyroidism of chronic kidney disease.
AB  - AIM: The most efficacious surgical treatment for renal hyperparathyroidism is
      still subject of research. Considering its low incidence rate of long-term
      relapse, "presumed" total parathyroidectomy without autotrasplantation (TP) may
      be indicated for secondary hyperparathyroidism (2HPT) in patients with chronic
      kidney disease (CKD), not eligible for kidney transplantation. The aim of this
      study was to analyse the TP long-term results in 2HPT haemodialysis (HD)
      patients. METHOD: Between January 2004 and October 2009, 25 2HPT HD patients, not
      eligible for kidney transplantation, underwent TP of at least four parathyroid
      glands. Clinical status and intact parathyroid hormone (iPTH) serum levels were
      assessed intraoperatively and during a 36-month follow-up. RESULTS: TP improved
      the typical clinical symptoms and a significant reduction of iPTH serum levels
      was achieved in each patient. Aparathyroidism was never observed; in case of
      severe postoperative hypocalcemia, hypocalcemic seizures were never reported and
      the long-term recurrence rate was 8%. Only one patient received a kidney
      transplantation. Postoperative cardiovascular events (hypertension, peripheral
      artery disease, arrhythmia, coronary or cerebrovascular disease) were observed in
      32% of cases and mortality rate was 16%. CONCLUSIONS: Considering its low long
      term relapse rate and the absence of postoperative aparathyroidism, TP may still
      be considered the treatment of choice in patients with aggressive forms of 2HPT
      or of advanced dialytic vintage, with no access to renal transplantation. In case
      of postoperative hypoparathyroidism, hypocalcaemia can be effectively managed by
      medical treatment.

PMID- 23140921
TI  - Arterial entrapment syndrome in the cubital fossa: a rare cause of acute stress
      related arterial thrombosis in a patient with brachial artery duplication.
AB  - Arterial entrapment syndrome (AES) at elbow level is very rare and to our
      knowledge no case of AES by lacertus fibrosus in the cubital fossa in presence of
      brachial artery duplication has been described to date. We describe a rare case
      of acute arterial thrombosis of one of two brachial arteries highlighted in the
      cubital fossa which developed after strenuous right elbow flexor muscle activity
      and hyper-extensions presumably related to AES by lacertus fibrosus at elbow
      level. A 43-year-old right-handed woman, experienced paleness, coldness and
      numbness of the right hand, after 8 consecutive hours of gardening. As she
      worked, her ipsilateral flexor elbow muscles remained in prolonged and
      inappropriate tension. Clinical examination evidenced the absence of radial
      artery pulse in the wrist and mild hypothermia in the second and third finger.
      During surgical exploration two anastomosed brachial arteries were detected in
      the cubital fossa under the lacertus fibrosus. The lateral superficial brachial
      artery was occluded. Intraoperative arteriography evidenced brachial artery
      duplication at the third superior of the arm and normal vascular pattern at the
      forearm level. In cases of unexplained atypical intermittent upper extremity
      claudication or acute ischemic symptoms an AES should always be ruled out,
      particularly when symptoms are exacerbated by strenuous upper extremity activity
      or when upper limb muscular hypertrophy is evident. In these cases a thorough
      dynamic clinical and instrumental examination is mandatory to confirm a diagnosis
      of AES and to avoid possible future ischemic complications.

PMID- 23140912
TI  - Confirming glycemic status in the Diabetes Prevention Program: implications for
      diagnosing diabetes in high risk adults.
AB  - AIMS: To examine the ability of fasting plasma glucose (FPG) and/or 2-h glucose
      to confirm diabetes and to determine the proportion of participants with HbA1c
      >=6.5%. METHODS: Diabetes confirmation rates were calculated after a single
      elevated FPG and/or 2-h glucose on an oral glucose tolerance test (OGTT) using a
      confirmatory OGTT performed within 6 weeks. RESULTS: 772 (24%) participants had
      elevated FPG or 2-h glucose on an OGTT that triggered a confirmation visit. There
      were 101 triggers on FPG alone, 574 on 2-h glucose alone, and 97 on both. Only
      47% of participants who triggered had confirmed diabetes. While the confirmation
      rate for FPG was higher than that for 2-h glucose, the larger number of 2-h
      glucose triggers resulted in 87% of confirmed cases triggering on 2-h glucose.
      Confirmation rates increased to 75% among persons with FPG >=126 mg/dl and HbA1c
      >=6.5%. CONCLUSIONS: Only half of the persons with elevated FPG and IGT were
      subsequently confirmed to have diabetes. At current diagnostic levels, more
      persons trigger on 2-h glucose than on FPG, but fewer of these persons have their
      diagnoses confirmed. In individuals with FPG >=126 mg/dl and HbA1c >=6.5%, the
      confirmation rate was increased.

PMID- 23140922
TI  - Diagnostic utility of thyroglobulin measurement in the fine needle aspirates from
      cervical lymph nodes: a case report.
AB  - Fine needle aspiration cytology (FNAC) is the more accurate diagnostic method for
      cervical lymph node (CLN) metastasis from differentiated thyroid cancers (DTC).
      However, FNAC diagnosis of cystic CLN is, in most cases, uninformative due to
      inadequate cellularity. Recently, thyroglobulin (Tg) detection in FNAC needle
      washout fluid has been shown to improve the diagnostic accuracy of FNAC, and its
      routine association with cytology is recommended. We here describe the case of a
      20 yr old girl complaining of the recent appearance of palpable non-painful
      laterocervical nodes in the neck. Ultrasound examination revealed the presence of
      3 cystic CLNs and 2 mixed thyroid nodules, with the larger one showing irregular
      margins. On the latter, and on 2 larger CLNs, FNAC was performed, and both Tg
      protein and mRNA were determined in the needle washout. The cytological analysis
      was not diagnostic for the two CLNs, while that of the thyroid nodule reported
      the presence of colloid and groups of thyrocytes with normal morphology. Both
      CLNs showed, however, high levels of Tg protein and were positive for Tg mRNA,
      suggestive of metastatic DTC. Based on these findings, the FNAC analysis was
      performed on the second smaller thyroid nodule suggesting (Tir4) the presence of
      PTC. The patient was then subjected to total thyroidectomy with lymph nodes
      resection of the central and homolateral compartments. The histological diagnosis
      confirmed the presence of a PTC in the small nodule and metastatic lymph nodes.
      In conclusion, this case confirms that the cytological diagnosis of cystic lymph
      nodes is challenging, and that the measurement of Tg protein and/or mRNA in the
      needle washout may overcome this limitation.

PMID- 23140923
TI  - The bovine pericardial patch in breast reconstruction: a case report.
AB  - In the last years there has been a growing demand of plastic surgery for soft
      tissue reconstruction. In response to this, many biological and synthetic devices
      have been produced, aiming to allow wide and complex body reshapings. Acellular
      dermal matrices are one of these devices, and are made of human or animal tissues
      made acellular after their sampling. They are used for cervical, breast and
      abdominal wall reconstruction. Tutopatch(r), generally used for face
      reconstruction or neurosurgery, is made of acellular bovine pericardium, and its
      high amount of collagen allows a fast tissue healing and a scaffold for the
      surrounding tissue regeneration. In our case report Tutopatch(r) has been used in
      immediate breast reconstruction after mastectomy. This device has been used to
      close laterally the subpectoral pocket, allowing a bigger volume prosthesis to be
      placed We have not experienced particular postoperatory complications, and after
      12 months of follow up we have found a valid functional and aesthetic result. We
      consider Tutopatch(r) as a valid alternative to other acellular dermal matrices
      specifically designed for breast reconstruction.

PMID- 23140924
TI  - Surgical strategy for the treatment of sporadic medullary thyroid carcinoma: our
      experience.
AB  - BACKGROUND: Medullary thyroid carcinoma (MTC) is a rare disease which accounts
      for approximately 5-9% of all thyroid cancers and originates from the calcitonin
      screening parafollicular C cells. MTC can be divided into two subgroups: sporadic
      (75%) or inherited (25%). The majority of patients with invasive MTC have
      metastasis to regional lymph nodes at the time of diagnosis, as evidenced by the
      frequent finding of persistently elevated calcitonin levels after thyroidectomy
      and the high rates of recurrence in the cervical lymph nodes reported in
      retrospective studies. OBJECTIVES: The purpose of the study is to review our
      single institution's experience with MTC since 1998 and to evaluate surgical
      strategy, patterns of lymph node metastases and calcitonin response to
      compartment-oriented lymphadenectomy in patients with primary or recurrent
      sporadic medullary thyroid carcinoma. METHODS: A retrospective review of 26
      patients treated for MTC at the "Antonio Cardarelli" Hospital referral center, in
      Naples, between 1998 and 2012. There were 18 female and 8 male patients, median
      age at presentation was 55 years, and median follow-up for survivors was 5 years.
      Total thyroidectomy was performed in all 26 patients; central compartment (CC)
      node dissection (level VI) in 12 (46%) patients; central plus lateral compartment
      (LC) node dissection (levels II, III, and IV) in 7 (27%) patients. 4 patients
      (15%) underwent reoperation for loco-regional recurrent/persistent MTC. Results.
      After a median post-surgical follow-up of 5 years (range 1-10 years), 63 % of
      patients were living disease-free, 15% were living with disease and/or
      persistently elevated calcitonin levels after surgery, 11% were deceased due to
      MTC and 11 % were lost to follow-up. CONCLUSIONS: We agree with most authors
      advocating for a total thyroidectomy and prophylactic central neck dissection in
      the setting of clinically detected MTC. Lateral neck dissection may be best
      reserved for patients with positive preoperative imaging. Nevertheless MTC has a
      high rate of lymph node metastases that are sub optimally detected preoperatively
      in the central compartment by neck ultrasound or intra-operatively by the
      surgeon, and reoperation is associated with a higher rate of surgical
      complications. In our limited experience, patients with thyroid confined nodular
      pathology, without nodal disease and unknown preoperative diagnosis of MTC,
      underwent only total thyroidectomy with a good prognosis.

PMID- 23140925
TI  - Laparoscopic approach in abdominal emergencies: a 5-year experience at a single
      center.
AB  - BACKGROUND: Laparoscopy is ever more common in both elective and emergency
      surgery. In fact, in abdominal emergencies it enables the resolution of
      preoperative diagnostic doubts as well as treatment of the underlying disease. We
      present a retrospective study of the results of a 5-year experience at a single
      center. PATIENTS AND METHODS: Between September 2006 and August 2011, 961
      patients were treated via laparoscopy, including 486 emergency cases (15
      gastroduodenal perforation; 165 acute cholecystitis; 255 acute appendicitis; 15
      pelvic inflammatory disease and non-specific abdominal pain [NSAP]; 36 small
      bowel obstruction). All procedures were conducted by a team trained in
      laparoscopic surgery. RESULTS: The conversion rate was 22/486 patients (4.53%). A
      definitive laparoscopic diagnosis was possible in over 96% of cases, and
      definitive treatment via laparoscopy was possible in most of these. CONCLUSIONS:
      Our own experience confirms the literature evidence that laparoscopy is a valid
      option in the surgical treatment of abdominal emergencies. In any case, it must
      be performed by a dedicated and highly experienced team. Correct patient
      selection is also important, to enable the most suitable approach for each given
      situation.

PMID- 23140926
TI  - Laparoscopic versus open total mesorectal excision for stage I-III mid and low
      rectal cancer: a retrospective 5 years analysis.
AB  - INTRODUCTION: Total mesorectal excision (TME) is the cornerstone of a correct
      surgical therapy for extraperitoneal rectal cancer. Aim of the study is to
      evaluate our 5 years experience confronting retrospectively laparoscopic (lap)
      TME in respect to its laparotomic (open) counterpart. PATIENTS AND METHODS: 30
      patients were treated laparoscopically for stage I-III extraperitoneal rectal
      cancer and retrospectively compared to a homogeneous group, stratified for sex,
      age, comorbidities and stage of disease. RESULTS: 30 days mortality was zero for
      both groups, while morbidity was 20% for the lap group and 36.6% for the open
      group. Mean lymph nodes harvested was 24 +/- 12 for the lap group, 26 +/- 14 for
      the open group (p > 0.05). Five years overall and disease free survival was
      respectively 82.2% and 81.4% in the lap group, 79.9% and 79.6% in the open group,
      without statistical significance (p>0.05). Discussion. Minimally invasive TME
      resulted a safe, effective and oncologically adequate procedure when
      retrospectively compared to its laparotomic counterpart, with 5 years overall
      survival and disease free survival reaching no statistical significance compared
      to the open approach, but with all the advantages of the laparoscopy such as less
      pain and blood loss, faster recovery, less morbidity and better cosmetics.
      CONCLUSIONS: Our study has retrospectively demonstrated that laparoscopic TME is
      feasible and oncologically effective, even if it remains a complex minimally
      invasive procedure, requiring adequate skill. More prospective, randomized
      studies are necessary to define such a procedure as the new gold standard in
      treatment of stage I-III extraperitoneal rectal cancer.

PMID- 23140927
TI  - Synchronous primary malignant tumors of the breast, caecum and sigma. Case
      report.
AB  - We present the case of a patient with a double adenocarcinoma of the right colon
      and sigma associated with a bilateral infiltrating ductal breast carcinoma. Sigma
      and caecum bowel cancers were diagnosed at colonoscopy, with computerized
      tomography staging, while breast cancer was found with screening mammography.
      Following right hemicolectomy , sigmoidectomy and bilateral mastectomy the
      histology confirmed the presence of colonic adenocarcinoma and infiltrating and
      in situ lobular cancer. This case report reviews the treatment of synchronous
      neoplasia.

PMID- 23140928
TI  - Colorectal retained foreign bodies per anum introduced. Three years retrospective
      study at Emergency Surgery Unit.
AB  - Colorectal foreign bodies per annum introduced are not exceptional. They can be
      classified as high-lying or low-lying, depending on their location relative to
      the recto-sigmoid junction. High-lying rectal foreign bodies sometimes require
      surgery; low-lying ones are often palpable by digital examination and can removed
      at bedside. No reliable data exist regarding the frequency of inserted rectal
      foreign bodies and the literature is largely anecdotal. We review our experience
      on patients almost all males and heterosexual with retained colorectal foreign
      bodies and their outcome in Surgical Emergency Unit of a Southern Italy
      University hospital.

PMID- 23140929
TI  - Pancreatic pseudocyst: case report and short literature review.
AB  - We report a case of pancreatic pseudocyst secondary to acute necrotizing
      pancreatitis treated with open cystogastrostomy. Following a literature review,
      we stress the enormous benefits offered by modern diagnostic techniques, and
      especially imaging techniques, for the diagnosis and monitoring of this disease.
      Treatment should be delayed for at least six weeks, following which the drainage
      by open surgery offers the best results and lowest morbidity and mortality,
      followed by laparoscopy and endoscopy, indicated in particular cases and in
      patients where open surgery is contraindicated.

PMID- 23140930
TI  - Colonic lipomas. Three surgical techniques for three different clinical cases.
AB  - Colonic lipomas larger than 2 cm in diameter are likely to be symptomatic. In
      some cases a complication is the first clinical sign. Massive lower intestinal
      bleeding or obstruction, acute bleeding, prolapse or perforation or, rarely,
      acute intussusception with intestinal obstruction require urgent surgery.
      Diagnosis is often made following colonoscopy, which can also have a therapeutic
      role. Imaging procedures such as CT has a secondary role. Patients with small
      asymptomatic colonic lipomas need regular follow up. For larger (diameter > 2 cm)
      and/or symptomatic lipomas, resection should be considered, although the choice
      between endoscopic or surgical resection remains controversial. We believe that
      even lipomas > 2 cm can safely be removed by endoscopic resection. If surgery is
      indicated, we consider laparoscopy to be the ideal approach in all patients for
      whom minimally invasive surgery is not contraindicated.

PMID- 23140931
TI  - Ocular traumatology in children. A retrospective study.
AB  - OBIECTIVE: This study assesses the descriptive epidemiology of children with eye
      injuries presenting to the Emergency Department of a non exclusive Paediatric
      University Hospital - First Division of Ophthalmology of "Sapienza" University of
      Rome - over a period of 12 years. STUDY DESIGN: A retrospective long term study
      of 12 years. PARTICIPANTS: All paediatric patients (up to 14 years of age)
      presenting with ocular injuries and hospitalized. METHODS: It was analyzed the
      incidence of the ocular trauma among males and females. The situation in which
      the trauma occurred, type of trauma (contusive or perforating), the presence of
      endo-bulbar foreign bodies, visual acuity outcome. RESULTS: There were 203
      patients who presented to the Emergency Department in the period examined.
      Contusive traumas were 130 (90 males, 40 females). The perforating trauma were 73
      (63 males, 10 females). The presence of an endo-bulbar foreign body was
      registered in 10 patients. A detailed analysis of the causes of the trauma is
      therefore provided. We evidence that males were almost exclusively involved in
      sport traumas (60 males versus 2 females), and in second instance accidental
      trauma is almost equally divided between two genders. CONCLUSIONS: Our
      retrospective study presents the paediatric cases of a non exclusive Paediatric
      University Hospital where 3% of ocular traumas requiring hospitalization were in
      children. Therefore our data could be useful in order to bring about the
      necessary preventive measures to minimize paediatric eye injuries.

PMID- 23140932
TI  - How new imaging techniques can aid in defining the cardiovascular profile of the
      high-risk patient.
AB  - Cardiovascular prevention has been developed in the last eight years producing an
      ever increasing amount of data requiring frequent updating. Studies using
      angiography to determine change in coronary obstruction have indicated
      progression, stabilization, or regression of coronary lesions associated with
      changes in plasma lipids and lipoproteins. Moreover, the guidelines on arterial
      hypertension published in 2007 listed the risk factors affecting prognosis but
      even by 2009 an update modified not only the list of risks, but even the
      philosophy behind the thought process which introduced as essential element in
      the prognosis of hypertension the ascertained existence of a damaged organ. Thus,
      the documentation of atherosclerotic vascular disease (plaques) and the
      quantification of its extension in the arterial tree became a determinant in the
      definition of cardiovascular risk. Magnetic Resonance (MRI) and coronary computed
      tomography (coro CT) applied to the heart and large vessels are the most
      promising methods.

PMID- 23140933
TI  - Tissue engineering: technological advances to improve its applications in
      reconstructive surgery.
AB  - BACKGROUND: Tremendous advances in biomaterials science and nanotechnologies,
      together with thorough research on stem cells, have recently promoted an
      intriguing development of regenerative medicine/tissue engineering. The
      nanotechnology represents a wide interdisciplinary field that implies the
      manipulation of different materials at nanometer level to achieve the creation of
      constructs that mimic the nanoscale-based architecture of native tissues. AIM:
      The purpose of this article is to highlight the significant new knowledges
      regarding this matter. EMERGING ACQUISITIONS: To widen the range of scaffold
      materials resort has been carried out to either recombinant DNA technology
      generated materials, such as a collagen-like protein, or the incorporation of
      bioactive molecules, such as RDG (arginine-glycine-aspartic acid), into synthetic
      products. Both the bottom-up and the top-down fabrication approaches may be
      properly used to respectively obtain sopramolecular architectures or, instead,
      micro-/nanostructures to incorporate them within a preexisting complex scaffold
      construct. Computer-aided design/manufacturing (CAD/CAM) scaffold technique
      allows to achieve patient-tailored organs. Stem cells, because of their peculiar
      properties - ability to proliferate, self-renew and specific cell-lineage
      differentiate under appropriate conditions - represent an attractive source for
      intriguing tissue engineering/regenerative medicine applications. FUTURE RESEARCH
      ACTIVITIES: New developments in the realization of different organs tissue
      engineering will depend on further progress of both the science of nanoscale
      based materials and the knowledge of stem cell biology. Moreover the in vivo
      tissue engineering appears to be the logical step of the current research.

PMID- 23140934
TI  - The lipid- and lipoprotein- [LDL-Lp(a)] apheresis techniques. Updating.
AB  - Therapeutic plasmapheresis allows the extracorporeal removal of plasmatic
      lipoproteins (Lipid-apheresis) (LA). It can be non selective (non specific), semi
      - selective or selective low density lipoprotein-lipoprotein(a) (specific [LDL-
      Lp(a)] apheresis) (Lipoprotein apheresis, LDLa). The LDL removal rate is a
      perfect parameter to assess the system efficiency. Plasma-Exchange (PEX) cannot
      be considered either specific nor, selective. In PEX the whole blood is separated
      into plasma and its corpuscular components usually through centrifugation or
      rather filtration. The corpuscular components mixed with albumin solution plus
      saline (NaCl 0.9%) solution at 20%-25%, are then reinfused to the patient, to
      substitute the plasma formerly removed. PEX eliminates atherogenic lipoproteins,
      but also other essential plasma proteins, such as albumin, immunoglobulins, and
      hemocoagulatory mediators. Cascade filtration (CF) is a method based on plasma
      separation and removal of plasma proteins through double filtration. During the
      CF two hollow-fiber filters with pores of different diameter are used to
      eliminate the plasma components of different weight and molecular diameter. A CF
      system uses a first polypropylene filter with 0.55 um diameter pores and a second
      one of diacetate of cellulose with 0.02 um pores. The first filter separates the
      whole blood, and the plasma is then perfused through a second filter which allows
      the recovery of molecules with a diameter lower than 0.02 um, and the removal of
      molecules larger in diameter as apoB100-containing lipoproteins. Since both
      albumin and immunoglobulins are not removed, or to a negligible extent, plasma
      expanders, substitution fluids, and in particular albumin, as occurs in PEX are
      not needed. CF however, is characterized by lower selectivity since removes also
      high density lipoprotein (HDL) particles which have an antiatherogenic activity.
      In the 80's, a variation of Lipid-apheresis has been developed which allows the
      LDL-cholesterol (LDLC) (-61%) and Lp(a) (-60%) removal from plasma through
      processing 3 liters of filtered plasma by means of lipid-specific
      thermofiltration, LDL immunoadsorption, heparin-induced LDL precipitation, LDL
      adsorption through dextran sulphate. More recently (90's) the DALI(r), and the
      Liposorber D(r) hemoperfusion systems, effective for apoB100- containing
      lipoproteins removal have been developed. All the above mentioned systems are
      established LDL-apheresis techniques referable to the generic definition of LDLa.
      However, this last definition cannot describe in an appropriate manner the
      removal of another highly atherogenic lipoprotein particle: the Lp(a). Thus it
      would be better to refer the above mentioned techniques to the wider scientific
      and technical concept of lipoprotein apheresis.

PMID- 23140935
TI  - Recurrent varicose veins of the legs. Analysis of a social problem.
AB  - The present study was aimed at assessing the experience of a single referral
      center with recurrent varicose veins of the legs (RVL) over the period 1993-2008.
      Among a total of 846 procedures for Leg Varices (LV), 74 procedures were for RVL
      (8.7%). The causes of recurrence were classified as classic: insufficient
      crossectomy (13); incompetent perforating veins (13); reticular phlebectasia
      (22); small saphenous vein insufficiency (9); accessory saphenous veins (4); and
      particular: post-hemodynamic treatment (5); incomplete stripping (1); Sapheno
      Femoral Junction (SFJ) vascularization (5); post-thermal ablation (2). For the
      "classic" RVL the treatment consisted essentially of completing the previous
      treatment, both if the problem was linked to an insufficient earlier treatment
      and if it was due to a later onset. The most common cause in our series was
      reticular phlebectasia; when the simple sclerosing injections are not sufficient,
      this was treated by phlebectomy according to Mueller. The "particular" cases
      classified as 1, 2 and 4 were also treated by completing the traditional
      stripping procedure (+ crossectomy if this had not been done previously),
      considered to be the gold standard. In the presence of a SFJ neo-vascularization,
      with or without cavernoma, approximately 5 cm of femoral vein were explored, the
      afferent vessels ligated and, if cavernoma was present, it was removed. Although
      inguinal neo-angiogenesis is a possible mechanism, some doubt can be raised as to
      its importance as a primary factor in causing recurrent varicose veins, rather
      than their being due to a preexisting vein left in situ because it was ignored,
      regarded as insignificant, or poorly evident. In conclusion, we stress that LV is
      a progressive disease, so the treatment is unlikely to be confined to a single
      procedure. It is important to plan adequate monitoring during follow-up, and to
      be ready to reoperate when new problems present that, if left, could lead the
      patient to doubt the validity and efficacy of the original treatment.

PMID- 23140936
TI  - Concordance between whole-cell matrix-assisted laser-desorption/ionization time
      of-flight mass spectrometry and multilocus sequence analysis approaches in
      species discrimination within the genus Pseudomonas.
AB  - Multilocus sequence analysis (MLSA) is one of the most accepted methods for the
      phylogenetic assignation of Pseudomonas strains to their corresponding species.
      Furthermore, updated databases are essential for correct bacterial identification
      and the number of Pseudomonas species is increasing continuously. Currently, 127
      species are validly described in Euzeby's List of Species with Standing in
      Nomenclature, and 29 novel species have been described since the publication of
      the last comprehensive MLSA phylogenetic study based on the sequences of the 16S
      rDNA, gyrB, rpoB and rpoD genes. Therefore, an update of the sequence database is
      presented, together with the analysis of the phylogeny of the genus Pseudomonas.
      Whole-cell matrix-assisted laser-desorption/ionization time-of-flight (WC-MALDI
      TOF) mass spectrometry (MS) analysis has been applied very recently to the
      identification of bacteria and is considered to be a fast and reliable method. A
      total of 133 type strains of the recognized species and subspecies in the genus
      Pseudomonas, together with other representative strains, were analyzed using this
      new technique, and the congruence between the WC-MALDI-TOF MS and MLSA techniques
      was assessed for the discrimination and correct species identification of the
      strains. The utility of both methods in the identification of environmental and
      clinical strains is discussed.

PMID- 23140937
TI  - Phalloplasty and urethroplasty in a boy with penile agenesis.
AB  - OBJECTIVE: New concepts in ambiguous genitalia have questioned the strategy of
      female gender reassignment in cases of penile agenesis. Hence, we present a video
      of the construction of a phallus according to the De Castro technique as an
      alternative approach for this devastating condition. METHODS: A 12-year-old boy
      with congenital penile agenesis and posterior urethra emerging in the distal
      rectum was selected. An ASTRA approach was used and a phallus was constructed
      with a skin flap from the abdominal wall, tubularized to produce a phallic
      appearance. A buccal mucosa graft was tubularized to create the new urethra.
      RESULTS: Immediate outcome was excellent. Partial dehiscence of the dorsal
      urethral sutures occurred and the patient started voiding through a scrotal
      urethrostomy at 9 months postoperatively. Phalloplasty provided an adequate male
      appearance with a good cosmetic aspect. CONCLUSION: The technique is a feasible
      alternative. A procedure in 2 stages by first creating the neourethra at a later
      date might be an interesting option to try to avoid the urethral complications
      observed. Long-term follow-up is however necessary to confirm the initial
      results.

PMID- 23140938
TI  - Minimally invasive surgical approach to excision of symptomatic ectopic inverted
      Y ureteral duplications.
AB  - Inverted-Y ureteral duplications are a rare duplication anomaly with few cases
      reported in the literature. We report a novel minimally invasive approach to
      managing inverted-Y duplications in two females who presented with continuous
      urinary incontinence and were found to have an ectopic insertion of the
      duplicated ureter. The ectopic segment was excised laparoscopically without
      complication in the outpatient setting with resultant cure of the continuous
      incontinence. This represents the first report of a laparoscopic approach to this
      rare anomaly.

PMID- 23140939
TI  - Studies on the isolation of Photobacterium damselae subsp. piscicida from
      diseased golden pompano (Trachinotus ovatus Linnaeus) and antibacterial agents
      sensitivity.
AB  - An epizootic occurred among cultured golden pompano (Trachinotus ovatus); it
      involved mass mortality on fish farms in Linshui in Hainan province, China, in
      2008. Diseased fish exhibited no obvious clinical signs, but pathological studies
      showed that nodules were scattered over the spleen and kidney. To investigate the
      nature of the pathogen, we studied the surviving fish, and a Gram-negative
      bacterium (designated strain TOS1) was isolated from the spleens of golden
      pompano. Pathogenicity assays revealed that TOS1 was virulent for golden pompano
      when they were challenged by intraperitoneal injection, and the lethal dose
      (LD(50)) was 1.1 * 10(6)colony forming units (CFU)g(-1). 16S rDNA gene sequence
      of TOS1 demonstrated high similarity (99%) to that of Photobacterium damselae
      subsp. piscicida. Phylogenetic analysis also showed a clear association of strain
      TOS1 with P. damselae subsp. piscicida, and this agreed with the results of
      morphological, physiological and biochemical identification. The results also
      showed that TOS1 was sensitive to norfloxacin, gentamicin,
      sulfamethoxazole/trimethoprim, neomycin, streptomycin and tetracycline, and was
      very sensitive to Psidium guajava and Atractylodes lancea (minimum bactericidal
      concentration, MBC=10(-6)g/mL). This paper describes a systematic study of P.
      damselae subsp. piscicida isolated from diseased golden pompano in China,
      including its sensitivity to different antibiotics and Chinese herbal extracts,
      which will contribute to the diagnosis and prevention of the associated disease.

PMID- 23140940
TI  - Molecular characterization of a Korean bovine parainfluenza virus type 3 isolate.
AB  - Bovine parainfluenza virus type 3 (BPIV-3) was isolated from Korean native cattle
      that presented clinical signs of mild pneumonia. The complete genome of a
      representative isolate (12Q061) was sequenced. The newly identified strain, which
      was found to be distinct from the previously reported genotypes A (BPIV-3a) and B
      (BPIV-3b) and closely related to the Chinese strain SD0835, was tentatively
      classified as genotype C (BPIV-3c). Our results suggest a relationship between
      BPIV-3 genetic variation and the geographic location of its isolation.
      Identification of these new BPIV-3 genotypes may facilitate the development of
      improved diagnostic methods and vaccines. This is to our knowledge the first
      report of the identification and molecular characterization of BPIV-3 in Korea.

PMID- 23140941
TI  - Genotyping of Staphylococcus aureus isolates from diseased poultry.
AB  - To gain insight into the genomic diversity of Staphylococcus aureus associated
      with diseases in domestic poultry, 131 isolates from clinically ill turkeys
      (n=80) and chickens (n = 51) were collected and genotyped using microarray
      hybridisations. MRSA isolates were subjected to spa and dru typing and their
      antimicrobial resistance geno- and phenotypes were determined. Most (68 out of
      80) turkey isolates belonged to the clonal complex (CC) 398. Seventeen of the 80
      isolates (21.2%) were MRSA. The most common MRSA type among turkeys was CC398
      MRSA-V (n = 8), but CC5-MRSA-III (n = 4), CC9-MRSA-IV (n = 2), CC398-MRSA-IV (n =
      2) and a single CC398-MRSA with an unidentified/truncated SCCmec element were
      also found. Among the chicken isolates, CC5 predominated (44 out of 51). Five of
      the chicken isolates were MRSA (9.8%), all belonging to CC398-MRSA-V. These data
      show that the current dissemination of livestock-associated MRSA also engulfs
      chickens and turkeys, and that MRSA surveillance among these species is
      warranted.

PMID- 23140942
TI  - UK investments in global infectious disease research 1997-2010: a case study.
AB  - BACKGROUND: Infectious diseases account for 15 million deaths per year worldwide,
      and disproportionately affect young people, elderly people, and the poorest
      sections of society. We aimed to describe the investments awarded to UK
      institutions for infectious disease research. METHODS: We systematically searched
      databases and websites for information on research studies from funding
      institutions and created a comprehensive database of infectious disease research
      projects for the period 1997-2010. We categorised studies and funding by disease,
      cross-cutting theme, and by a research and development value chain describing the
      type of science. Regression analyses were reported with Spearman's rank
      correlation coefficient to establish the relation between research investment,
      mortality, and disease burden as measured by disability-adjusted life years
      (DALYs). FINDINGS: We identified 6170 funded studies, with a total research
      investment of UKL2.6 billion. Studies with a clear global health component
      represented 35.6% of all funding (L927 million). By disease, HIV received L461
      million (17.7%), malaria L346 million (13.3%), tuberculosis L149 million (5.7%),
      influenza L80 million (3.1%), and hepatitis C L60 million (2.3%). We compared
      funding with disease burden (DALYs and mortality) to show low levels of
      investment relative to burden for gastrointestinal infections (L254 million,
      9.7%), some neglected tropical diseases (L184 million, 7.1%), and antimicrobial
      resistance (L96 million, 3.7%). Virology was the highest funded category (L1
      billion, 38.4%). Leading funding sources were the Wellcome Trust (L688 million,
      26.4%) and the Medical Research Council (L673 million, 25.8%). INTERPRETATION:
      Research funding has to be aligned with prevailing and projected global
      infectious disease burden. Funding agencies and industry need to openly document
      their research investments to redress any inequities in resource allocation.
      FUNDING: None.

PMID- 23140943
TI  - Mapping the terrain of investment in global infectious diseases.

PMID- 23140945
TI  - Childhood chronic inflammatory demyelinating polyradiculoneuropathy: combined
      analysis of a large cohort and eleven published series.
AB  - The clinical presentation, disease course, response to treatment, and long-term
      outcome of thirty childhood chronic inflammatory demyelinating
      polyradiculoneuropathy (CIDP) patients are presented representing the largest
      cohort reported to date. Most children (60%) presented with chronic (>8-weeks)
      symptom-onset while a smaller proportion showed sub-acute (4-8 weeks) or acute
      (''GBS-like''; <4 weeks) onset of disease. No gender predilection was observed.
      The majority of patients had a relapsing (70%) versus a monophasic (30%) temporal
      profile. Most received initial IVIG monotherapy; 80% showing a good response.
      Long-term follow-up (mean=3.8 years) was available for 23 patients; 45% were off
      all immunomodulatory medications, demonstrating no detectable (55%) or minimal
      (43%) clinical deficits. Our data were compared with 11 previously published
      childhood CIDP series providing a comprehensive review of 143 childhood CIDP
      cases. The combined initial or first-line treatment response across all studies
      was favourable for IVIG (79% patients) and corticosteroids (84% patients).
      Response to first-line plasma exchange was poor (only 14% patients improved)
      although it may offer some transient or partial benefit as an adjuvant or
      temporary therapy for selected patients. The combined long-term outcome of our
      cohort and the literature reveals a favourable prognosis for most patients. The
      combined modified Rankin scale decreased from 3.7 (at presentation) to 0.7 (at
      last follow-up). This review provides important data pertaining to clinical
      course, treatment response and long-term outcome of this relatively uncommon
      paediatric autoimmune disease.

PMID- 23140946
TI  - Older age as a poor prognostic sign in patients with pyogenic liver abscess.
AB  - BACKGROUND: Previous studies have focused on the role of age as a prognostic
      factor in pyogenic liver abscess (PLA) and results have been controversial. The
      aim of this study was to compare the clinical characteristics of PLA in elderly
      (age >=65 years) and non-elderly patients in order to identify any differences so
      that an early diagnosis can be made and appropriate therapeutic measures can be
      instituted promptly. METHODS: We performed a retrospective analysis of patients
      with PLA. The demographic and clinical features, laboratory and imaging findings,
      management, and clinical outcomes of elderly and non-elderly patients were
      studied. RESULTS: Between January 2000 and December 2010 inclusive, 319 patients
      had PLA; 168 (52.7%) were aged >=65 years. Elderly patients were more likely to
      have acute onset of symptoms (4.2 vs. 5.3 days, p < 0.04), co-morbidities, and
      respiratory symptoms (25.6% vs. 14.6%, p < 0.01). They also had lower serum
      bilirubin (28.1 vs. 37.1 MUmol/l, p < 0.04), alanine aminotransferase (71.6 vs.
      94.3 U/l, p < 0.02), and glycosylated hemoglobin (8.1% vs. 10%, p < 0.01), and
      more often had septal lobulation (64.3% vs. 54.3%, p < 0.04) and pneumobilia
      (10.1% vs. 4.0%, p < 0.02). Moreover, they required a longer duration of oral
      antibiotics (2.63 vs. 2.05 weeks, p < 0.01) and had a higher incidence of acute
      coronary syndrome during the illness (7.7% vs. 2.0%, p < 0.01). Gram-negative
      organisms were the dominant isolates in both groups, but the elderly had a lower
      incidence of Gram-positive infections (5.4% vs. 13.2%, p < 0.01). Lastly, old age
      was associated with local recurrence of PLA (odds ratio (OR) 3.1, 95% confidence
      interval (CI) 1.0-9.7, p < 0.04) and mortality (OR 3.17, 95% CI 1.25-8.04, p =
      0.015). CONCLUSIONS: Elderly patients tend to have a more atypical presentation
      in PLA, for which clinicians should be on high alert. We found older age to be
      associated with a higher recurrence of PLA and a higher mortality rate.

PMID- 23140944
TI  - Rev1 recruits ung to switch regions and enhances du glycosylation for
      immunoglobulin class switch DNA recombination.
AB  - By diversifying the biological effector functions of antibodies, class switch DNA
      recombination (CSR) plays a critical role in the maturation of the immune
      response. It is initiated by activation-induced cytidine deaminase (AID)-mediated
      deoxycytosine deamination, yielding deoxyuridine (dU), and dU glycosylation by
      uracil DNA glycosylase (Ung) in antibody switch (S) region DNA. Here we showed
      that the translesion DNA synthesis polymerase Rev1 directly interacted with Ung
      and targeted in an AID-dependent and Ung-independent fashion the S regions
      undergoing CSR. Rev1(-/-)Ung(+/+) B cells reduced Ung recruitment to S regions,
      DNA-dU glycosylation, and CSR. Together with an S region spectrum of mutations
      similar to that of Rev1(+/+)Ung(-/-) B cells, this suggests that Rev1 operates in
      the same pathway as Ung, as emphasized by further decreased CSR in Rev1(-/-)Msh2(
      /-) B cells. Rescue of CSR in Rev1(-/-) B cells by a catalytically inactive Rev1
      mutant shows that the important role of Rev1 in CSR is mediated by Rev1's
      scaffolding function, not its enzymatic function.

PMID- 23140947
TI  - The efficacy of cefmetazole against pyelonephritis caused by extended-spectrum
      beta-lactamase-producing Enterobacteriaceae.
AB  - OBJECTIVES: Urinary tract infections (UTIs) caused by extended-spectrum beta
      lactamase (ESBL)-producing Enterobacteriaceae are on the increase. Although
      cefmetazole is stable in vitro against the hydrolyzing activity of ESBLs, no
      clinical study has ever evaluated its role in infections caused by these
      organisms. We therefore evaluated the efficacy of cefmetazole compared to
      carbapenems against pyelonephritis caused by ESBL-producing Enterobacteriaceae.
      METHODS: A retrospective chart review was conducted at a tertiary care hospital
      from August 2008 to July 2010. Chart reviews were done for patients with ESBL
      producing organisms in urine identified in the microbiology database. Patients
      who were treated with cefmetazole were compared to those treated with
      carbapenems. The clinical and bacteriological cure rates at 4 weeks after
      completion of therapy were evaluated. RESULTS: Two hundred and fifty-six urine
      cultures growing ESBL-producing organisms were identified during the study
      period. Ten patients treated with cefmetazole and 12 patients treated with
      carbapenems were evaluated. There was no difference in clinical (9/10 vs. 12/12,
      p = 0.46) or bacteriological cure rate (5/7 vs. 6/7, p = 1.00) at 4 weeks after
      the completion of therapy. There was no difference in the incidence of adverse
      effects (2/10 vs. 2/12, p = 1.00). CONCLUSIONS: Cefmetazole may be a useful
      option for the treatment of UTIs caused by ESBL-producing organisms. Prospective
      and larger sized studies are needed to confirm our findings.

PMID- 23140948
TI  - Universal nucleic acid sequence-based amplification for simultaneous
      amplification of messengerRNAs and microRNAs.
AB  - A universal NASBA assay is presented for simultaneous amplification of multiple
      microRNA (miRNA) and messengerRNA (mRNA) sequences. First, miRNA and mRNA
      sequences are reverse transcribed using tailed reverse transcription primer pairs
      containing a gene-specific and an non-specific region. For reverse transcription
      of small miRNA molecules a non-specific region is incorporated into a structured
      stem-loop reverse transcription primer. Second, a universal NASBA primer pair
      that recognizes the tagged cDNA molecules enables a simultaneous, transcription
      based amplification reaction (NASBA) of all different cDNA molecules in one
      reaction. The NASBA products (RNA copies) are detected by gene-specific DNA
      probes immobilized on a biochip. By using the multiplex reverse transcription
      combined with the universal NASBA amplification up to 14 different mRNA and miRNA
      sequences can be specifically amplified and detected in parallel. In comparison
      with standard multiplex NASBA assays this approach strongly enhances the
      multiplex capacity of NASBA-based amplification reactions. Furthermore
      simultaneous assaying of different RNA classes can be achieved that might be
      beneficial for studying miRNA-based regulation of gene expression or for RNA
      based tumor diagnostics.

PMID- 23140949
TI  - Adaptive approach for variable noise suppression on laser-induced breakdown
      spectroscopy responses using stationary wavelet transform.
AB  - Spectral signals are often corrupted by noise during their acquisition and
      transmission. Signal processing refers to a variety of operations that can be
      carried out on measurements in order to enhance the quality of information. In
      this sense, signal denoising is used to reduce noise distortions while keeping
      alterations of the important signal features to a minimum. The minimization of
      noise is a highly critical task since, in many cases, there is no prior knowledge
      of the signal or of the noise. In the context of denoising, wavelet
      transformation has become a valuable tool. The present paper proposes a noise
      reduction technique for suppressing noise in laser-induced breakdown spectroscopy
      (LIBS) signals using wavelet transform. An extension of the Donoho's scheme,
      which uses a redundant form of wavelet transformation and an adaptive threshold
      estimation method, is suggested. Capabilities and results achieved on denoising
      processes of artificial signals and actual spectroscopic data, both corrupted by
      noise with changing intensities, are presented. In order to better consolidate
      the gains so far achieved by the proposed strategy, a comparison with alternative
      approaches, as well as with traditional techniques, is also made.

PMID- 23140950
TI  - Optimization of headspace experimental factors to determine chlorophenols in
      water by means of headspace solid-phase microextraction and gas chromatography
      coupled with mass spectrometry and parallel factor analysis.
AB  - In this work an analytical procedure based on headspace solid-phase
      microextraction and gas chromatography coupled with mass spectrometry (HS-SPME
      GC/MS) is proposed to determine chlorophenols with prior derivatization step to
      improve analyte volatility and therefore the decision limit (CCalpha). After
      optimization, the analytical procedure was applied to analyze river water
      samples. The following analytes are studied: 2,4-dichlorophenol (2,4-DCP), 2,4,6
      trichlorophenol (2,4,6-TrCP), 2,3,4,6-tetrachlorophenol (2,4,6-TeCP) and
      pentachlorophenol (PCP). A D-optimal design is used to study the parameters
      affecting the HS-SPME process and the derivatization step. Four experimental
      factors at two levels and one factor at three levels were considered: (i)
      equilibrium/extraction temperature, (ii) extraction time, (iii) sample volume,
      (iv) agitation time and (v) equilibrium time. In addition two interactions
      between four of them were considered. The D-optimal design enables the reduction
      of the number of experiments from 48 to 18 while maintaining enough precision in
      the estimation of the effects. As every analysis took 1h, the design is blocked
      in 2 days. The second-order property of the PARAFAC (parallel factor analysis)
      decomposition avoids the need of fitting a new calibration model each time that
      the experimental conditions change. In consequence, the standardized loadings in
      the sample mode estimated by a PARAFAC decomposition are the response used in the
      design because they are proportional to the amount of analyte extracted. It has
      been found that block effect is significant and that 60 degrees C equilibrium
      temperature together with 25min extraction time are necessary to achieve the best
      extraction for the chlorophenols analyzed. The other factors and interactions
      were not significant. After that, a calibration based in a PARAFAC2 decomposition
      provided the following values of CCalpha: 120, 208, 86, 39ngL(-1) for 2,4-DCP,
      2,4,6-TrCP, 2,3,4,5-TeCP and PCP respectively for a probability of false positive
      set at 5%. Also, the accuracy (trueness and precision) of the procedure is
      assessed. Finally, river water samples have been analyzed with the proposed
      method showing the absence of the chlorophenols studied.

PMID- 23140951
TI  - Combining local wavelength information and ensemble learning to enhance the
      specificity of class modeling techniques: Identification of food geographical
      origins and adulteration.
AB  - Class modeling techniques are required to tackle various one-class problems.
      Because the training of class models is based on the target class and the origins
      of future test objects usually cannot be exactly predefined, the criteria for
      feature selection of class models are not very straightforward. Although feature
      reduction can be expected to improve class models performance, more features
      retained can provide a sufficient description of the sought-for class. This paper
      suggests a strategy to balance class description and model specificity by
      ensemble learning of sub-models based on separate local wavelength intervals. The
      acceptance or rejection of a future object can be explicitly determined by
      examining its acceptance frequency by sub-models. Considering the lack of
      information about sub-model independence, we propose to use a data-driven method
      to control the sensitivity of the ensemble model by cross validation. In this
      way, all the wavelength intervals are used for class description and the local
      wavelength intervals are highlighted to enhance the ability to detect out-of
      class objects. The proposed strategy was performed on one-class partial least
      squares (OCPLS) and soft independent modeling of class analogy (SIMCA). By
      analysis of two infrared spectral data sets, one for geographical origin
      identification of white tea and the other for discrimination of adulterations in
      pure sesame oil, the proposed ensemble class modeling method was demonstrated to
      have similar sensitivity and better specificity compared with total-spectrum
      SIMCA and OCPLS models. The results indicate local spectral information can be
      extracted to enhance class model specificity.

PMID- 23140952
TI  - On the construction of experimental designs for a given task by jointly
      optimizing several quality criteria: Pareto-optimal experimental designs.
AB  - Experimental designs for a given task should be selected on the base of the
      problem being solved and of some criteria that measure their quality. There are
      several such criteria because there are several aspects to be taken into account
      when making a choice. The most used criteria are probably the so-called
      alphabetical optimality criteria (for example, the A-, E-, and D-criteria related
      to the joint estimation of the coefficients, or the I- and G-criteria related to
      the prediction variance). Selecting a proper design to solve a problem implies
      finding a balance among these several criteria that measure the performance of
      the design in different aspects. Technically this is a problem of multi-criteria
      optimization, which can be tackled from different views. The approach presented
      here addresses the problem in its real vector nature, so that ad hoc experimental
      designs are generated with an algorithm based on evolutionary algorithms to find
      the Pareto-optimal front. There is not theoretical limit to the number of
      criteria that can be studied and, contrary to other approaches, no just one
      experimental design is computed but a set of experimental designs all of them
      with the property of being Pareto-optimal in the criteria needed by the user.
      Besides, the use of an evolutionary algorithm makes it possible to search in both
      continuous and discrete domains and avoid the need of having a set of candidate
      points, usual in exchange algorithms.

PMID- 23140953
TI  - Determination of chemical oxygen demand of nitrogenous organic compounds in
      wastewater using synergetic photoelectrocatalytic oxidation effect at TiO2
      nanostructured electrode.
AB  - Chemical oxygen demand (COD) is one of the most important parameters in water
      quality assessment and monitoring. The natural degradation of nitrogenous organic
      compounds (NOCs) in water requires significant amounts of oxygen. In the
      determination of standard COD however, NOCs are persistent compounds that cannot
      be completely oxidized even in the most oxidative chemical environments, i.e. the
      reaction media that contain high concentrations of dichromate in strong acid at
      high temperature. Consequently, the measured COD values of wastewater samples
      containing NOCs are commonly lower than theoretical COD values and do not reflect
      the actual oxygen demand of the water body. This problem is partially alleviated
      when the photoelectrochemical method for COD determination (PeCOD) based on
      nanostructured TiO(2) photoanode is utilized. To completely overcome this
      problem, a synergetic photoelectrochemical oxidation effect in thin layer cells
      is used to achieve complete oxidation of NOCs. This is done by the simple
      addition of a hydroxyl organic compound (i.e. glucose) into the test sample
      before the PeCOD measurement. Preliminary experimental results demonstrate that
      the synergetic PeCOD method provides an effective and reliable means to measure
      COD values of NOC-containing pollutants without the need for toxic or expensive
      reagents.

PMID- 23140954
TI  - Determination of ammonium in aqueous samples using new headspace dynamic in
      syringe liquid-phase microextraction with in situ derivitazation coupled with
      liquid chromatography-fluorescence detection.
AB  - A new simultaneous derivatization and extraction method for the preconcentration
      of ammonia using new one-step headspace dynamic in-syringe liquid-phase
      microextraction with in situ derivatization was developed for the trace
      determination of ammonium in aqueous samples by liquid chromatography with
      fluorescence detection (LC-FLD). The acceptor phase (as derivatization reagent)
      containing o-phthaldehyde and sodium sulfite was held within a syringe barrel and
      immersed in the headspace of sample container. The gaseous ammonia from the
      alkalized aqueous sample formed a stable isoindole derivative with the acceptor
      phase inside the syringe barrel through the reciprocated movements of plunger.
      After derivatization-cum-extraction, the acceptor phase was directly injected
      into LC-FLD for analysis. Parameters affecting the ammonia evolution and the
      extraction/derivatization efficiency such as sample matrix, pH, temperature,
      sampling time, and the composition of derivatization reagent, reaction
      temperature, and frequency of reciprocated plunger, were studied thoroughly.
      Results indicated that the maximum extraction efficiency was obtained by using
      100MUL derivatization reagent in a 1-mL gastight syringe under 8 reciprocated
      movements of plunger per min to extract ammonia evolved from a 20mL alkalized
      aqueous solution at 70 degrees C (preheated 4min) with 380rpm stirring for 8min.
      The detection was linear in the concentration range of 0.625-10MUM with the
      correlation coefficient of 0.9967 and detection limit of 0.33MUM (5.6ng mL(-1))
      based on SN(-1)=3. The method was applied successfully to determine ammonium in
      real water samples without any prior cleanup of the samples, and has been proved
      to be a simple, sensitive, efficient and cost-effective procedure for trace
      ammonium determination in aqueous samples.

PMID- 23140955
TI  - pH-controlled dispersive liquid-liquid microextraction for the analysis of
      ionisable compounds in complex matrices: Case study of ochratoxin A in cereals.
AB  - A new sample preparation procedure, termed pH-controlled dispersive liquid-liquid
      microextraction (pH-DLLME), has been developed for the analysis of ionisable
      compounds in highly complex matrices. This DLLME mode, intended to improve the
      selectivity and to expand the application range of DLLME, is based on two
      successive DLLMEs conducted at opposite pH values. pH-DLLME was applied to
      determination of ochratoxin A (OTA) in cereals. The hydrophobic matrix
      interferences in the raw methanol extract (disperser, 1mL) were removed by a
      first DLLME (I DLLME) performed at pH 8 to reduce the solubility of OTA in the
      extractant (CCl(4), 400MUL). The pH of the aqueous phase was then adjusted to 2,
      and the analyte was extracted and concentrated by a second DLLME (extractant,
      150MUL C(2)H(4)Br(2)). The main factors influencing the efficiency of pH-DLLME
      including type and volume of I DLLME extractant, as well as the parameters
      affecting the OTA extraction by II DLLME, were studied in detail. Under optimum
      conditions, the method has detection and quantification limits of 0.019 and
      0.062MUg kg(-1), respectively, with OTA recoveries in the range of 81.2-90.1%
      (n=3). The accuracy of the analytical procedure, evaluated with a reference
      material (cereal naturally contaminated with OTA), is acceptable (accuracy of
      85.6%+/-1.7, n=5). The applicability of pH-DLLME to the selective extraction of
      other ionisable compounds, such as acidic and basic pharmaceutical products was
      also demonstrated. The additional advantages of pH-DLLME are a higher selectivity
      and the extension of this microextraction technique to highly complex matrices.

PMID- 23140956
TI  - Online trapping and enrichment ultra performance liquid chromatography-tandem
      mass spectrometry method for sensitive measurement of "arginine-asymmetric
      dimethylarginine cycle" biomarkers in human exhaled breath condensate.
AB  - BACKGROUND: Exhaled breath condensate (EBC) is a biofluid collected non
      invasively that, enabling the measurement of several biomarkers, has proven
      useful in the study of airway inflammatory diseases, including asthma, COPD and
      cystic fibrosis. To the best of our knowledge, there is no previous report of any
      analytical method to detect ADMA in EBC. OBJECTIVES: Aim of this work was to
      develop an online sample trapping and enrichment system, coupled with an UPLC
      MS/MS method, for simultaneous quantification of seven metabolites related to
      "Arginine-ADMA cycle", using the isotopic dilution. METHODS: Butylated EBC
      samples were trapped in an online cartridge, washed before and after each
      injection with cleanup solution to remove matrix components and switched inline
      into the high pressure analytical column. Multiple reaction monitoring in
      positive mode was used for analyte quantification by tandem mass spectrometry.
      RESULTS: Validation studies were performed in EBC to examine accuracy, precision
      and robustness of the method. For each compound, the calibration curves showed a
      coefficient of correlation (r(2)) greater than 0.992. Accuracy (%Bias) was <3%
      except for NMMA and H-Arg (<20%), intra- and inter-assay precision (expressed as
      CV%) were within +/-20% and recovery ranged from 97.1 to 102.8% for all analytes.
      Inter-day variability analysis on 20 EBC of adult subjects did not demonstrate
      any significant variation of quantitative data for each metabolite. ADMA and SDMA
      mean concentrations (MUmolL(-1)), measured in EBC samples of asthmatic
      adolescents are significantly increased (p<0.0001) than in normal controls
      (0.0040+/-0.0021 vs. 0.0012+/-0.0005 and 0.0020+/-0.0015 vs. 0.0002+/-0.0001,
      respectively), as well the ADMA/Tyr (0.34+/-0.09 vs. 0.12+/-0.02, p<0.0001) and
      the SDMA/Tyr ratio (0.10+/-0.04 vs. 0.015+/-0.004, p<0.0001). CONCLUSIONS: The
      proposed method features simple specimen preparation, maintenance of an excellent
      peak shape of all metabolites and reduced matrix effects as well mass
      spectrometer noise. Moreover, the possibility to perform different cycles of
      enrichment, using large injection volumes, compensated for the low concentration
      of analytes contained in EBC, leading to a good analytical sensitivity.
      Preliminary data obtained from asthmatic and healthy adolescents, demonstrated
      that the analytical method applied to EBC seems suitable not only for research
      purposes, but also for clinical routinely analysis.

PMID- 23140957
TI  - Development of a new multi-residue laser diode thermal desorption atmospheric
      pressure chemical ionization tandem mass spectrometry method for the detection
      and quantification of pesticides and pharmaceuticals in wastewater samples.
AB  - A new solid phase extraction (SPE) method coupled to a high throughput sample
      analysis technique was developed for the simultaneous determination of nine
      selected emerging contaminants in wastewater (atrazine, desethylatrazine, 17beta
      estradiol, ethynylestradiol, norethindrone, caffeine, carbamazepine, diclofenac
      and sulfamethoxazole). We specifically included pharmaceutical compounds from
      multiple therapeutic classes, as well as pesticides. Sample pre-concentration and
      clean-up was performed using a mixed-mode SPE cartridge (Strata ABW) having both
      cation and anion exchange properties, followed by analysis by laser diode thermal
      desorption atmospheric pressure chemical ionization coupled to tandem mass
      spectrometry (LDTD-APCI-MS/MS). The LDTD interface is a new high-throughput
      sample introduction method, which reduces total analysis time to less than 15s
      per sample as compared to minutes with traditional liquid-chromatography coupled
      to tandem mass spectrometry (LC-MS/MS). Several SPE parameters were evaluated in
      order to optimize recovery efficiencies when extracting analytes from wastewater,
      such as the nature of the stationary phase, the loading flow rate, the extraction
      pH, the volume and composition of the washing solution and the initial sample
      volume. The method was successfully applied to real wastewater samples from the
      primary sedimentation tank of a municipal wastewater treatment plant. Recoveries
      of target compounds from wastewater ranged from 78% to 106%, the limit of
      detection ranged from 30 to 122ng L(-1) while the limit of quantification ranged
      from 90 to 370ng L(-1). Calibration curves in the wastewater matrix showed good
      linearity (R(2)>=0.991) for all target analytes and the intraday and interday
      coefficient of variation was below 15%, reflecting a good precision.

PMID- 23140958
TI  - A potentiometric chiral sensor for L-Phenylalanine based on crosslinked
      polymethylacrylic acid-polycarbazole hybrid molecularly imprinted polymer.
AB  - A novel chiral molecularly imprinted polymer (MIP) sensor for L-Phenylalanine has
      been developed, which is constructed by electrochemically driven cross-linking a
      pendant polymer precursor, poly[2-(N-carbazolyl)ethyl methacrylate-co-meth
      acrylic acid]s (PCEMMAs). In this MIP sensing material, the recognition sites,
      the insulating polymethylacrylic acid (PMAA), were covalently bonded to the
      conducting polycarbazole which could be used as signal transfer interface between
      recognition layer and electrode. The mole ratio of copolymerizing monomers, 2-(N
      carbazolyl) ethyl methacrylate:methylacrylic acid (CE:MAA), and the scanning
      cycles of electropolymerization were adjusted during the preparation of MIP
      sensing material. The optimized conditions, CE:MAA=3:2 and 20 scanning cycles,
      were obtained. And then the properties of MIP films were characterized by atomic
      force microscope (AFM), X-ray photoelectron spectroscopy (XPS) and water contact
      angle. Open circuit potential-time technique was used to estimate the
      enantioselectivity of the MIP sensor. The results indicate that the promising
      sensor preferentially responses L-Phenylalanine (L-Phe) over D-Phenylalanine (D
      Phe) with a selectivity coefficient K(D)(L)=5.75*10(-4) and the limit of
      detection (LOD) is 1.37MUM, which reveals its good enantioselectivity and
      sensitivity.

PMID- 23140959
TI  - Electrochemiluminescent disposable cholesterol biosensor based on avidin-biotin
      assembling with the electroformed luminescent conducting polymer poly(luminol
      biotinylated pyrrole).
AB  - An electrochemiluminescent cholesterol disposable biosensor has been prepared by
      the formation of assembled layers on gold screen-printed cells. The detection
      layer is based on the electro-formation of new luminol copolymers with different
      synthesized biotinylated pyrroles prepared by click-chemistry, offering a new
      transduction layer with new electroluminescent properties on biosensors. The
      electrochemiluminescence (ECL) luminol copolymers are electroformed by cyclic
      voltammetry (five cycles) at pH 7.0 uses a10(-3)M biotinylated pyrrole-luminol
      ratio of 1:10 in PBS buffer. With respect to the recognition layer, cholesterol
      oxidase was biotinylated by incubation with biotin vinyl sulfone, and immobilized
      on the copolymer by avidin-biotin interaction. The analytical signal of the
      biosensor is the ECL enzymatic initial rate working in chronoamperometric mode at
      0.5V excitation potential with 10s between pulses at pH 9.5. The disposable
      device offers a cholesterol linear range from 1.5*10(-5)M to 8.0*10(-4)M with a
      limit of detection of 1.47*10(-5)M and accuracy of 7.9% for 9.0*10(-5)M and 14.1%
      for 2.0*10(-4)M, (n=5). Satisfactory results were obtained for cholesterol
      determination in serum samples compared to a reference procedure.

PMID- 23140960
TI  - Foreword to the virus research special issue on "retroviral RNA, protein co
      factors and chaperones".

PMID- 23140961
TI  - Updated guidelines for device-based therapy of cardiac rhythm abnormalities.

PMID- 23140962
TI  - Use of transcatheter heart valves for a valve-in-valve implantation in patients
      with degenerated aortic bioprosthesis: technical considerations and results.
AB  - OBJECTIVE: Transcatheter aortic valve implantation has been used to treat high
      risk patients with bioprosthetic valve degeneration (valve-in-valve). We report
      our experience with transcatheter aortic valve implantation in the treatment of
      degenerated biologic aortic valve prostheses and discuss factors that can
      influence the outcome. METHODS: From February 2009 to October 2011, 278 patients
      underwent transcatheter aortic valve implantation, of whom 23 underwent a valve
      in-valve procedure with the Edwards Sapien valve to treat a failing bioprostheses
      in the aortic position. Eight of these valves were stentless bioprostheses.
      Thirteen patients had valve failure resulting predominantly from stenosis, and
      the remaining resulting from regurgitation. RESULTS: Mean age was 76.9 +/- 14.4
      years. The mean logistic EuroSCORE was 31.8% +/- 20.3% and the Society of
      Thoracic Surgeons score was 7.6% +/- 5.4%. All patients were New York Heart
      Association class III or IV. The majority of the operations (21/23) were
      performed via the transapical route. Procedural success was 100%, although 1
      patient with a degenerated homograft needed immediate placement of a second valve
      because of low placement of the first. The reduction in the mean gradient was
      31.2 +/- 17.06 mm Hg to 9.13 +/- 4.9 mm Hg. In those patients with predominant
      aortic regurgitation (9/23), reduction in aortic regurgitation was achieved in
      all. The median length of stay was 11.7 days (range, 3-44 days). In-hospital
      and/or 30-day mortality was 0%. CONCLUSIONS: Valve-in-valve is a safe and
      feasible alternative to treat high-risk patients with failing aortic
      bioprostheses. The early results are excellent, with improvement seen in
      hemodynamics.

PMID- 23140964
TI  - A prospective, randomized comparison of 3 contemporary bioprosthetic aortic
      valves: should hemodynamic performance influence device selection?
AB  - OBJECTIVE: Latest generation biologic aortic valve prostheses were designed to
      improve hemodynamic performance. We sought to determine whether there are
      clinically important early differences among these devices. METHODS: Three
      hundred adults with severe aortic valve stenosis undergoing aortic valve
      replacement were randomized to receive the Edwards Magna, Sorin Mitroflow, or St.
      Jude Epic bioprostheses (n = 100, n = 101, n = 99, respectively). Early
      hemodynamic performance was studied by echocardiography. RESULTS: Mean patient
      age was 76 +/- 8 years and there were 203 men (68%). There were no significant
      differences in baseline characteristics among implant groups. Early mortality was
      1.7%, and there were no differences in early adverse events. Postoperative
      echocardiography showed small but statistically significant differences overall
      between the Magna, Mitroflow, and Epic valves in mean gradient (14.2 mm Hg, 16.3
      mm Hg, 16.5 mm Hg, respectively; P = .011), aortic valve area (2.05 cm(2), 1.88
      cm(2), 1.86 cm(2), respectively; P = .012), and indexed aortic valve area (1.05
      cm(2)/m(2), 0.97 cm(2)/m(2), 0.95 cm(2)/m(2), respectively; P = .012). Prosthetic
      performance was similar among all with a small (<=21 mm) aortic annulus. Patients
      who received the Magna device with a 23-mm annulus had slightly greater indexed
      aortic valve area; those with >23 mm had a slightly lower transprosthetic
      gradient. Analogous trends were found when data were stratified by either
      commercial implant size or echocardiography-determined aortic annulus size.
      Severe patient-prosthesis mismatch was infrequent overall and was similarly low
      among devices (P value not significant). CONCLUSIONS: This prospective,
      randomized comparison reveals that there are small but consistent early
      postoperative hemodynamic differences among current third-generation porcine and
      pericardial aortic valve prostheses. The 3 valves studied performed equally well
      in patients with a small (<=21 mm) aortic annulus. The Magna valve had a slightly
      lower mean gradient in those with larger annular size (>23 mm). Longitudinal
      follow-up of these randomized cohorts is essential to determine late clinical
      implications of these early postoperative findings.

PMID- 23140967
TI  - What is the culprit in coronary anomalies?

PMID- 23140968
TI  - Awake thoracic surgery for secondary spontaneous pneumothorax: another
      advancement.

PMID- 23140969
TI  - Hemostatic management in complex aortic surgery: a role for multiple electrode
      aggregometry and modified rotational thromboelastometry.

PMID- 23140970
TI  - Perventricular closure of postinfarct septal rupture revisited.

PMID- 23140971
TI  - Can we implant valved mitral prosthesis within all kinds of mitral rings through
      a transapical approach?

PMID- 23140972
TI  - Early surgical treatment for infective endocarditis: Does it come at the expense
      of worse neurologic outcomes?

PMID- 23140973
TI  - Is the cause of death in hypertrophic cardiomyopathy low pressure gradient in
      left ventricular outflow?

PMID- 23140974
TI  - Rescue coronary artery bypass grafting in isolated life-threatening right
      ventricular failure after aortic valve replacement.

PMID- 23140975
TI  - Neurocognitive outcomes in older adults after transcatheter aortic valve
      replacement.

PMID- 23140977
TI  - Prevalence, incidence, and classification of chronic fatigue syndrome in Olmsted
      County, Minnesota, as estimated using the Rochester Epidemiology Project.
AB  - OBJECTIVE: To estimate the prevalence and incidence of chronic fatigue syndrome
      in Olmsted County, Minnesota, using the 1994 case definition and describe
      exclusionary and comorbid conditions observed in patients who presented for
      evaluation of long-standing fatigue. PATIENTS AND METHODS: We conducted a
      retrospective medical record review of potential cases of chronic fatigue
      syndrome identified from January 1, 1998, through December 31, 2002, using the
      Rochester Epidemiology Project, a population-based database. Patients were
      classified as having chronic fatigue syndrome if the medical record review
      documented fatigue of 6 months' duration, at least 4 of 8 chronic fatigue
      syndrome-defining symptoms, and symptoms that interfered with daily work or
      activities. Patients not meeting all of the criteria were classified as having
      insufficient/idiopathic fatigue. RESULTS: We identified 686 potential patients
      with chronic fatigue, 2 of whom declined consent for medical record review. Of
      the remaining 684 patients, 151 (22%) met criteria for chronic fatigue syndrome
      or insufficient/idiopathic fatigue. The overall prevalence and incidence of
      chronic fatigue syndrome and insufficient/idiopathic fatigue were 71.34 per
      100,000 persons and 13.16 per 100,000 person-years vs 73.70 per 100,000 persons
      and 13.58 per 100,000 person-years, respectively. The potential cases included
      482 patients (70%) who had an exclusionary condition, and almost half the
      patients who met either criterion had at least one nonexclusionary comorbid
      condition. CONCLUSION: The incidence and prevalence of chronic fatigue syndrome
      and insufficient/idiopathic fatigue are relatively low in Olmsted County. Careful
      clinical evaluation to identify whether fatigue could be attributed to
      exclusionary or comorbid conditions rather than chronic fatigue syndrome itself
      will ensure appropriate assessment for patients without chronic fatigue syndrome.

PMID- 23140978
TI  - Synthesis of TAT peptide-tagged PEGylated chitosan nanoparticles for siRNA
      delivery targeting neurodegenerative diseases.
AB  - Delivery of therapeutic molecules to the brain for the treatment of
      Neurodegenerative diseases (ND) is a challenging task. This manuscript introduces
      a novel scheme of synthesizing peptide-tagged polyethylene glycol (PEG)ylated
      chitosan polymer to develop nanoparticles for siRNA delivery for use in ND.
      Specifically, this manuscript proposes a facile chemoselective conjugation of
      monomethoxy PEG, at the C2 hydroxyl group of chitosan polymer, with conjugation
      of PEG to a cell-penetrating peptide, Trans-Activator of Transcription. The
      synthesized Chitosan-PEG-TAT polymer was used to form the nanoparticles of
      approximately 5 nm, complexing siRNA to be delivered in neuronal cells (Neuro
      2a), with no/minimal toxicity. The various intermediates and the final product
      formed during the synthesis were characterized using (1)H Nuclear Magnetic
      Resonance and Fourier Transform Infrared Spectroscopy spectra. The morphological
      details of the nanoparticles were studied using Transmission Electron Microscopy.
      The nanoparticles were tested to deliver a functional siRNA against the Ataxin-1
      gene in an in-vitro established model of a ND Spinocerebellar ataxia (SCA1) over
      expressing ataxin protein. The results indicate successful suppression of the
      SCA1 protein following 48 h of transfection. Result of this study has potential
      in ND like SCA, Parkinson's, Alzheimer's and others.

PMID- 23140976
TI  - 2012 ACCF/AHA/HRS focused update of the 2008 guidelines for device-based therapy
      of cardiac rhythm abnormalities: a report of the American College of Cardiology
      Foundation/American Heart Association Task Force on Practice Guidelines.

PMID- 23140979
TI  - [Real per capita health spending by age and sex in Spain (1998-2008): changes and
      effects on public healthcare expenditure projections].
AB  - OBJECTIVES: To analyze changes in real per capita spending by age and sex from
      1998 to 2008 in Spain, and to assess their effects on public healthcare
      expenditure projections. METHODS: Age- and sex-related expenditure profiles in
      constant terms were estimated for the Spanish population for 3 distinct years
      (1998, 2003 and 2008) by using data from hospital records and several National
      Health Surveys. These profiles were used to compare actual healthcare expenditure
      for 2003 and 2008 with the projections obtained by considering 1998 as the base
      year and by applying the methodology used by the Working Group on Aging of the
      European Union. RESULTS: The average annual growth rate of real per capita
      spending per person from 1998 to 2008 was 2.79%, which was higher than the GDP
      per capita growth rate (1.90%), basically due to its high rate of increase in the
      second half of the decade. From 1998 to 2008, per capita healthcare expenditure
      increased in most age groups, particularly in the groups aged 45-49 years, 60-64
      years and 75 years and older. Projections of per capita expenditure in constant
      terms covered the real value observed for 2003, but were below the real value for
      2008. CONCLUSIONS: Changes in the quantity and quality of healthcare services
      consumed by each person are an important factor in changes in healthcare
      expenditure and must be included in spending projections.

PMID- 23140980
TI  - [Effective interventions to reduce absenteeism among hospital nurses].
AB  - OBJECTIVES: To select and summarize the interventions that have proved effective
      in reducing absenteeism among hospital nurses. METHODS: A scoping review was
      conducted through a literature search using Medline, Web of Science, Cinahl,
      Embase, Lilacs, Cuiden and Cochrane Library Plus databases. Of a total of 361
      articles extracted, 15 were finally selected for this review. RESULTS: The
      implementation of multifaceted support or physical training programs can produce
      positive results in terms of reducing absenteeism among hospital nurses.
      Cognitive-behavioral type interventions require studies with larger samples to
      provide conclusive results. Establishing more flexible working shifts may also
      reduce absenteeism rates, although again studies with larger samples are needed.
      Programs aimed at managing change developed by nurses themselves, participatory
      management of professional relations, the support provided by supervisors who are
      opposed to hierarchical leadership styles, and wage supplements that reward the
      lack of absence can also reduce these types of indicators. CONCLUSIONS:
      Absenteeism can be considered as a final result and a consequence of the level of
      job satisfaction. The effectiveness of interventions to reduce absenteeism among
      hospital nurses will no doubt largely depend on the ability of these
      interventions to increase the job satisfaction of these workers.

PMID- 23140981
TI  - [European innovation partnership on active and healthy aging: moving from policy
      to action].
AB  - Demographic change and aging are a common challenge in Europe. The rising number
      of elderly people will need support at home, and will consume more healthcare
      services, putting further pressure on the welfare system. Collaborative,
      integrated and people-centered care provision, whether in hospitals, homes or in
      the community, is a way forward to sustainable and efficient care systems.
      Innovative treatments to address chronic diseases and the functional decline of
      older people will enable them to live longer in better health and with a better
      quality of life. To fully unleash the potential of aging in the European Union,
      the European Commission -within its Innovation Union policy- launched the first
      European Innovation Partnership on Active and Healthy Ageing (EIP AHA). Promoting
      engagement and partnerships among all stakeholders in the healthcare chain is
      essential. This article describes the theoretical foundations, the development
      and expectations of the initiative, and its first actions. 

PMID- 23140982
TI  - [Incidence and prevalence of diabetes in an adult population of Madrid (Spain): a
      study using computerized medical records in primary care].

PMID- 23140983
TI  - Tetramethylpyrazine accelerates the function recovery of traumatic spinal cord in
      rat model by attenuating inflammation.
AB  - In the present study, we explored the effects of tetramethylpyrazine (TMP), an
      alkaloid extracted from the Chinese herbal medicine Ligusticum wallichii Franchat
      (chuanxiong), on a rat model of contusion spinal cord injury (SCI). The contusion
      SCI model was induced in rats by a modified Allen's weight-drop method with a
      severity of 5 g * 50 mm impacting on the T10 segment. In the TMP treatment group,
      rats were injected intraperitoneally (i.p.) with TMP (200mg/kg), every 24h for 5
      days, starting half an hour after contusion SCI. The control group was treated
      with saline. Compared with the control group, the TMP group significantly
      ameliorated the recovery of hindlimb function of rats. TMP treatment
      significantly reduced the expression of macrophage migration inhibitory factor,
      nuclear factor kappaappa B, pro-inflammatory cytokine interleukin-18 and
      neutrophil infiltration. On the other hand, TMP enhanced the expression of
      inhibitor kappaappa B and anti-inflammation cytokine interleukin-10. In
      conclusion, our results demonstrate that TMP inhibits the development of
      inflammation and tissue injury associated with spinal cord contusion in rats
      which may improve the rats' hindlimb function.

PMID- 23140984
TI  - Acoustic impairment is a distinguishable clinical feature of Asidan/SCA36.
AB  - OBJECTIVE: To investigate acoustic function of Asidan/spinocerebellar ataxia type
      36 (SCA36) in which sensorineural hearing loss may be found as one of
      extracerebellar symptom that can be a distinguishable feature from other
      degenerative ataxias. METHODS: Acoustic function in the groups of normal control
      (n=31), Asidan/SCA36 (n=13), cortical cerebellar atrophy (CCA, n=28), multiple
      system atrophy of cerebellar predominance (MSA-C, n=48), SCA31 (n=4), and other
      forms of SCAs (n=14) was evaluated by pure tone average (PTA) calculated by the
      results of audiogram and brainstem auditory evoked potentials (BAEPs). RESULTS:
      PTA was significantly decreased in Asidan/SCA36 in comparison to normal control
      and other ataxic groups, but not significant within other ataxic groups and
      normal control. In comparison to other groups, Asidan/SCA36 showed a constant
      depression at 7 different frequencies in audiogram, especially at 4000 and 8000
      Hz. BAEPs in 2 Asidan/SCA36 cases suggested possible involvement in the inner ear
      or the peripheral part of the auditory system. PTA in Asidan/SCA36 cases
      significantly correlated with their severity of ataxia. CONCLUSIONS: In addition
      to signs for motor neuron involvement, acoustic impairment in Asidan/SCA36 is
      another characteristic clinical feature that is distinguishable from other forms
      of SCAs.

PMID- 23140985
TI  - Lavage treatment of painful jaw movements at disc displacement without reduction.
      A randomized controlled trial in a short-term perspective.
AB  - This study compared the short-term efficacy of two treatments (local anesthetics
      (A) and local anesthetics and lavage (AL)) in patients with permanently displaced
      discs and temporomandibular disorder (TMD) pain. 45 patients participated in the
      single-blind randomized controlled trial. All patients had received: a Research
      Diagnostic Criteria/TMD diagnosis of disc displacement without reduction; and
      magnetic resonance imaging confirmation of non-reducing disc displacement.
      Participants were randomized to treatment with A or AL and were assessed at
      baseline and at 1 and 3 month follow-ups. The primary outcome measure defining
      success was reduction in pain intensity of at least 30% during jaw movement. At
      the 3 month follow-up, the success rate was 76% for A and 55% for AL. Both groups
      reported similar pain relief with no significant difference between the groups.
      Similar trends were observed for outcome measures in the physical functioning,
      emotional functioning, and global improvement domains with no significant
      difference between the groups. Use of lavage to supplement extra-articular local
      anesthetic treatment of painful jaw movements at non-reducing discs does not
      appear to improve TMD pain and mouth opening capacity in the short term.

PMID- 23140986
TI  - Novel coumarin derivatives bearing N-benzyl pyridinium moiety: potent and dual
      binding site acetylcholinesterase inhibitors.
AB  - A novel series of coumarin derivatives linked to benzyl pyridinium group were
      synthesized and biologically evaluated as inhibitors of both acetylcholinesterase
      (AChE) and butyrylcholinesterase (BuChE). The enzyme inhibitory activity of
      synthesized compounds was measured using colorimetric Ellman's method. It was
      revealed that compounds 3e, 3h, 3l, 3r and 3s have shown higher activity compared
      with donepezil hydrochloride as standard drug. Most of the compounds in these
      series had nanomolar range IC(50) in which compound 3r (IC(50) = 0.11 nM) was the
      most active compound against acetylcholinesterase enzyme.

PMID- 23140987
TI  - Anti-infective and herbicidal activity of N-substituted 2-aminobenzothiazoles.
AB  - In this study, a series of N-substituted 2-aminobenzothiazoles was prepared
      according to a recently developed method. Twelve compounds were tested for their
      activity related to the inhibition of photosynthetic electron transport (PET) in
      spinach (Spinacia oleracea L.) chloroplasts. Primary in vitro screening of the
      discussed compounds was also performed against fungal, bacterial and
      mycobacterial species. The biological activities of some compounds were
      comparable or higher than the standards phenoxymethylpenicillin or pyrazinamide.
      The most effective compounds demonstrated insignificant toxicity against the
      human monocytic leukemia THP-1 cell line. For all compounds, the structure
      activity relationships are discussed.

PMID- 23140988
TI  - Placental concentrations of heavy metals in a mother-child cohort.
AB  - Heavy metals are environmental contaminants with properties known to be toxic for
      wildlife and humans. Despite strong concerns about their harmful effects, little
      information is available on intrauterine exposure in humans. The aim of this
      study was to evaluate prenatal exposure to As, Cd, Cr, Hg, Mn, and Pb and its
      association with maternal factors in a population-based mother-child cohort in
      Southern Spain. Between 2000 and 2002, 700 pregnant women were recruited and 137
      placentas from the cohort were randomly selected and analyzed for the selected
      metals by atomic absorption. Maternal sociodemographic and lifestyle factors were
      obtained by questionnaire after delivery. Bivariate analysis and multivariate
      linear regression were performed. Cd and Mn concentrations were detected in all
      placentas, while Cr, Pb, and Hg were found in 98.5%, 35.0%, and 30.7% of samples,
      respectively. The highest concentrations were observed for Pb (mean: 94.80 ng/g
      wet weight of placenta), followed by Mn (63.80 ng/g), Cr (63.70 ng/g), Cd (3.45
      ng/g), and Hg (0.024 ng/g). Arsenic was not detected in any sample. Gestational
      age and smoking during pregnancy were associated with placental Cd
      concentrations, while no factor appeared to influence concentrations of Cr, Hg,
      Mn, or Pb. In comparison to results of European studies, these concentrations are
      in a low-intermediate position. Studies are required to investigate the factors
      contributing to early exposure to heavy metals and to determine how placental
      transfer of these toxic compounds may affect children's health.

PMID- 23140989
TI  - The many faces of pleiotropy.
AB  - Pleiotropy is the well-established phenomenon of a single gene affecting multiple
      traits. It has long played a central role in theoretical, experimental, and
      clinical research in genetics, development, molecular biology, evolution, and
      medicine. In recent years, genomic techniques have brought data to bear on
      fundamental questions about the nature and extent of pleiotropy. However, these
      efforts are plagued by conceptual difficulties derived from disparate meanings
      and interpretations of pleiotropy. Here, we describe distinct uses of the
      pleiotropy concept and explain the pitfalls associated with applying empirical
      data to them. We conclude that, for any question about the nature or extent of
      pleiotropy, the appropriate answer is always 'What do you mean?'.

PMID- 23140990
TI  - Biodiversity and functional genomics in the human microbiome.
AB  - Over the course of our lives, humans are colonized by a tremendous diversity of
      commensal microbes, which comprise the human microbiome. The collective genetic
      potential (metagenome) of the human microbiome is orders of magnitude more than
      the human genome, and it profoundly affects human health and disease in ways we
      are only beginning to understand. Advances in computing and high-throughput
      sequencing have enabled population-level surveys such as MetaHIT and the recently
      released Human Microbiome Project, detailed investigations of the microbiome in
      human disease, and mechanistic studies employing gnotobiotic model organisms. The
      resulting knowledge of human microbiome composition, function, and range of
      variation across multiple body sites has begun to assemble a rich picture of
      commensal host-microbe and microbe-microbe interactions as well as their roles in
      human health and disease and their potential as diagnostic and therapeutic tools.

PMID- 23140991
TI  - Treatment of canine leishmaniosis with aminosidine at an optimized dosage
      regimen: a pilot open clinical trial.
AB  - Leishmaniosis due to Leishmania infantum (Syn: L. chagasi) is one of the most
      common diseases of dogs in Mediterranean countries and also has zoonotic
      potential. The aim of this study was to evaluate the efficacy of an optimized
      dosage regimen of aminosidine for the treatment of canine leishmaniosis (CanL) in
      terms of clinical remission, restoration of clinicopathological abnormalities,
      evolution of antibody titer, lymph node and bone marrow parasitic density and of
      PCR-based parasitological cure. Twelve non-uremic dogs without proteinuria,
      presenting clinical signs of CanL were included in the study. The diagnosis was
      confirmed by serology, microscopy and PCR of lymph node and bone marrow samples.
      Aminosidine was administered subcutaneously at the dose of 15 mg/kg body weight,
      once daily, for 21 consecutive days. A partial remission of the clinical signs,
      amelioration of clinicopathological abnormalities such as anemia, lymphopenia,
      hyperproteinemia, hyperglobulinemia, and reduced albumin/globulin ratio and
      reduced lymph node and bone marrow parasitic density were witnessed, although
      parasitological cure was not achieved. Since data are not supportive enough for
      the use of aminosidine as an alternative treatment, a large-scale controlled
      clinical trial using this optimized dosage regimen of aminosidine is warranted to
      compare efficacy against currently used drugs.

PMID- 23140992
TI  - Large diameter metal on metal articulations. Comparison of total hip arthroplasty
      and hip resurfacing arthroplasty.
AB  - The use of large diameter metal bearing total hip arthroplasty (THA) and hip
      resurfacing arthroplasty (HRA) increased in popularity in the last decade. More
      recent literature has highlighted the effect of head size in patient outcomes.
      Data was obtained from the Australian Orthopaedic Association National Joint
      Replacement Registry (AOA-NJRR) to evaluate the Birmingham (MoM) bearing surface
      when used with THA and HRA. There is no difference in the overall rate of
      revision between the THA and HRA but head size has a significant effect on
      revision rate. The data show that small diameter metal bearings in HRA (below
      50mm) have a higher rate of revision than large diameter metal bearings in HRA
      (equal to and above 50mm) (P<.001). Conversely the large diameter metal bearings
      in THA have a higher rate of revision than the small diameter metal bearings in
      THA (P=.027). The revision rate for large diameter HRA compared to small diameter
      THA is not significantly different P=.670. We recommend caution when choosing
      either a large diameter (>=50mm) metal on metal THA or small diameter (<50mm)
      HRA.

PMID- 23140993
TI  - The laterality of ovulation: how far does it matter?
AB  - The laterality of ovulation, or the side at which ovulation occurs, was the
      subject of much research in the past century, but it was discussed merely as an
      interesting physiologic issue in all primates. In the last few years, the
      increasing development of infertility treatment has drawn the attention of
      researchers to the clinical aspects of this phenomenon. In the review, we discuss
      the nature of ovulation side and how far it can influence pregnancy outcome in
      infertile women treated with different modalities.

PMID- 23140994
TI  - Vagus nerve stimulation: urgent need for the critical reappraisal of clinical
      effectiveness.

PMID- 23140995
TI  - GABRG2 rs211037 polymorphism and epilepsy: a systematic review and meta-analysis.
AB  - PURPOSE: The gamma-aminobutyric acid A receptor, gamma 2 (GABRG2) gene encodes
      the GABRgamma2 protein, which has been implicated in susceptibility to epilepsy.
      Several studies have examined a possible link between the exonic GABRG2 rs211037
      locus and susceptibility to febrile seizure (FS) and idiopathic generalized
      epilepsy (IGE), however results have been inconclusive. We therefore performed a
      systematic review and meta-analysis to examine whether this polymorphism is
      associated with FS or IGE. METHODS: Eight studies comprising 1871 epilepsy
      patients and 1387 controls, which evaluated association of the GABRG2 rs211037
      polymorphism with susceptibility to epilepsy, were included in this meta
      analysis. Meta-analysis was carried out separately for FS and IGE. RESULTS: Meta
      analysis showed a significant association between this polymorphism and
      susceptibility to FS in a codominant (TT vs. CC, OR 0.47, 95% CI 0.30-0.73,
      p=0.0008 and TT vs. CT, OR 0.59, 95% CI 0.42-0.83, p=0.003) and dominant (OR
      0.54, 95% CI 0.39-0.75, p=0.0002) genetic models, influenced by two studies with
      small sample size. Neither allele nor genotype association was observed with IGE.
      CONCLUSION: This study showed significant association of GABRG2 rs211037 with
      susceptibility to FS, caused by two studies with small sample sizes, however the
      possibility of false positive results due to the effect of significant studies
      for FS cannot be excluded. Future studies with larger sample sizes of these
      patients are suggested to verify the results.

PMID- 23140996
TI  - Cell fractionation on pH-responsive chitosan surface.
AB  - The purpose of this study is to demonstrate pH-responsive chitosan is able to be
      used for cell fractionation under precise adjustment of medium pH. Cells were
      first seeded to attach on chitosan surface at medium pH 7.20 for 24 h. After
      raising medium pH to 7.65 for 1 h, cells with elongated morphology possessed
      rapider detachment rate and cells with round shape detached at a lesser rate.
      Therefore, successful cell separation has been achieved by choosing appropriate
      cell combination with different detachment rates without additional antibody or
      enzyme treatment and extensive washing steps. Furthermore, the method also could
      be applied to specific manipulation of viable cell populations from tissue
      specimen. Most importantly and interestingly, the efficiency of cell
      fractionation of our system could be theoretically predicted according to the
      individual cell detachment rate on pH-responsive chitosan surface, without
      considering the presence of heterotypic cells.

PMID- 23140997
TI  - Effects of aspect ratios of stem cells on lineage commitments with and without
      induction media.
AB  - The present study is aimed to examine the shape effect on lineage commitment of
      stem cells in growth medium free of external chemical induction factors. Aspect
      ratios (ARs) of cells were controlled by micropatterns with cell-adhesive
      microislands of AR 1, 2 and 8 on the potent nonfouling background of
      poly(ethylene glycol) hydrogels, and the single stem cells were well shaped for
      19 days. Mesenchymal stem cells (MSCs) derived from rat bone marrow were cultured
      in osteogenic medium, adipogenic medium, mixed coinduction medium, and also
      growth medium; alkaline phosphatase (ALP) and oil droplets were employed as
      indicators of osteoblasts and adipocytes, respectively. Those indicators were
      well observed in all of three induction media as early as day 7, and also in
      growth medium at a longer culture time till day 13. While a significant monotonic
      decrease of adipogenesis was observed with the increase of AR, a non-monotonic
      change of osteogenesis was found with optimal AR about 2. The relative gene
      expressions further verified the above findings. As a result, cell shape itself
      is an inherent cue to regulate stem cell differentiation, let alone with or
      without external chemical induction factors. Such a shape effect disappeared upon
      addition of a microfilament inhibitor cytochalasin D or a Rho-associated protein
      kinase (ROCK) inhibitor Y-27632. So, formation of cytoskeleton is necessary for
      the shape effect, and the ROCK-pathway-related cell tension is responsible for
      the shape effect on the lineage commitment of stem cells even in growth medium.

PMID- 23140998
TI  - The effect of growth factor environment on fibroblast morphological response to
      substrate stiffness.
AB  - According to conventional understanding regarding dependence of cell behavior on
      substrate stiffness, tissue cells typically remain round on soft substrates but
      spread on stiff substrates. The current studies were carried out to learn if the
      growth factor environment influenced the foregoing relationship. Using standard
      methods, we prepared planar (2D) polyacrylamide (PA) gels ranging from 0.5 to 40
      kPa and covalently cross-linked with fibronectin and collagen at concentrations
      ranging from 2.5 to 50 MUg/ml. We carried out experiments with fibroblasts
      varying in their ability to form actin stress fibers and focal adhesions. In
      fetal bovine serum (FBS) containing medium--the growth factor environment in
      which most studies on cell spreading and substrate stiffness have been carried
      out--cell spreading increased with increasing substrate stiffness and adhesion
      ligand density. However, in platelet-derived growth factor (PDGF) containing
      medium, cell spreading was relatively independent of substrate stiffness and
      adhesion ligand density except little cell attachment occurred in the complete
      absence of cross-linked adhesion ligands. If cell contraction was blocked with
      blebbistatin, then cell spreading in FBS-containing medium became independent of
      substrate stiffness. The findings suggest that under growth factor conditions
      that stimulate global cell contraction (FBS), cell spreading cannot occur unless
      adhesion ligand density and substrate stiffness result in cell-substrate
      interactions strong enough to resist and overcome the inward tractional force.
      Under growth factor conditions that stimulate global cell protrusion (PDGF), such
      resistance is not required.

PMID- 23140999
TI  - Biomineralization inspired surface engineering of nanocarriers for pH-responsive,
      targeted drug delivery.
AB  - Recent insight into the molecular mechanisms of natural biomineralization has
      enabled biomimetic synthesis of functional organic-inorganic hybrid materials
      under mild reaction conditions. Here, we describe a novel method to construct
      organic-inorganic hybrid on mesoporous silica nanoparticles by utilizing
      electrostatically absorbed hyaluronic acid (HA) as a reaction site for deposition
      of calcium phosphate (CaP) minerals. The addition of another layer of HA on the
      CaP surfaces not only stabilizes the nanocomposites but also confers target
      ability toward CD44 overexpressed cancer cells. The nanomaterials enable
      controlled release of loaded anticancer drugs in acidic subcellular environments
      after receptor mediated endocytosis. More importantly, our study demonstrated
      that the cancer targeting nanomaterials dramatically enhanced cellular uptake and
      cytotoxicity toward breast carcinoma cells. These results thus open new
      opportunities for biomineralization guided nanostructure assemblies with great
      potential for biomedical applications.

PMID- 23141000
TI  - Maternal pre-pregnancy underweight and fetal growth in relation to institute of
      medicine recommendations for gestational weight gain.
AB  - PURPOSE: Maternal nutritional status is one of the most important factors of
      fetal growth and development. Consequently, the currently increasing prevalence
      of underweight women worldwide has come in the focus of interest of perinatal
      medicine. The aim of the study was to assess the effect of low pre-pregnancy body
      mass index (BMI) on fetal growth. MATERIALS AND METHODS: Data on 4678 pregnant
      women and their neonates were retrospectively analyzed. Pre-pregnancy BMI of
      study women was categorized according to the WHO standards. Fetal growth was
      assessed by birth weight and birth length, birth weight for gestational age, and
      ponderal index. RESULTS: Study group included 351 (7.6%) women with
      pregestational BMI<18.5kg/m(2), while all women with pregestational BMI 18.5
      25kg/m(2) (n=3688; 78.8%) served as a control group. The mean birth weight and
      birth length of neonates born to underweight mothers were by 167g and 0.8cm lower
      in comparison with the neonates born to mothers of normal nutritional status,
      respectively (P<0.001 both). The prevalence of small for gestational age (SGA)
      births was twofold that found in the control group of mothers of normal
      nutritional status (9.7% vs. 4.9%; P<0.001). The inappropriately low gestational
      weight gain additionally increased the rate of SGA infants in the group of
      mothers with low pre-pregnancy BMI (21.4% vs. 10.4%; P=0.02). Pre-pregnancy BMI
      category did not influence neonatal growth symmetry. CONCLUSION: Low maternal
      pregestational BMI is associated with fetal growth assessment. Improvement of the
      maternal nutritional status before pregnancy can increase the likelihood of
      perinatal outcome.

PMID- 23141001
TI  - Shopping behaviors of low-income families during a 1-month period of time.
AB  - OBJECTIVE: To explore food shopping behaviors among low-income families over the
      course of the month. DESIGN: Two researchers conducted 13 90-minute focus groups.
      SETTING: Two community organizations serving low-income populations and a
      university campus. PARTICIPANTS: Low-income adults (n = 72) who were the primary
      household food shoppers and who had at least 1 child less than 18 years old.
      VARIABLES MEASURED: Shopping behavior changes during 1 month. ANALYSIS: Focus
      groups were recorded, transcribed, and coded independently by 2 researchers.
      Descriptive statistics were used to evaluate sociodemographic variables such as
      age, sex, race/ethnicity, and participation in food assistance programs. RESULTS:
      Economics played a key role in participants' food shopping behaviors and
      influenced food availability throughout the month. To overcome economic barriers,
      participants used food and emergency assistance programs and engaged in menu
      planning, price matching, storing food, using credit cards, and receiving
      financial assistance from family members and/or neighbors. CONCLUSIONS AND
      IMPLICATIONS: Low-income families made strategic decisions to maintain a food
      supply throughout the month. These results suggest limited economics throughout
      the month may hinder families' ability to consume a varied, nutrient-rich diet,
      which may have an impact on future health status.

PMID- 23141002
TI  - Combined laparoscopic-assisted nephrectomy, augmentation ureterocystoplasty and
      Mitrofanoff appendicovesicostomy.
AB  - Conventional and robotic-assisted laparoscopy is being used for more and more
      complex urological procedures in children. There have recently been reports of
      laparoscopic or laparoscopic-assisted appendicovesicostomies in children. We
      report a case of combined laparoscopic-assisted nephrectomy, augmentation
      ureterocystoplasty and Mitrofanoff appendicovesicostomy in a 5-year-old boy with
      valve bladder syndrome.

PMID- 23141003
TI  - [Doubt about catheter-based renal sympathetic denervation for resistant
      hypertension].

PMID- 23141004
TI  - [From anti-hypertension treatment to management of blood pressure].

PMID- 23141005
TI  - [From "antihypertensive treatment" to "antihypertensive management"].

PMID- 23141006
TI  - [Biomarkers of endothelial dysfunction and risk of early organ damage: a
      comparison between patients with primary aldosteronism and essential
      hypertension].
AB  - OBJECTIVE: To compare plasma concentrations of biomarkers of endothelial
      dysfunction between patients with primary aldosteronism (PA) and essential
      hypertension (EH), and to determine whether elevated levels of these biomarkers
      could predict development of early organ damage. METHODS: Thirty-six PA patients
      and 39 EH patients matched for age, sex, blood pressure and duration of
      hypertension were included in this study. Plasma levels of biomarkers reflecting
      endothelial dysfunction (von Willebrand factor, vWF; soluble intercellular
      adhesion molecule 1, sICAM-1; and oxidized low density lipoprotein, ox-LDL) were
      detected and compared between PA and EH patients. Left ventricular mass index
      (LVMI) determined by echocardiography, 24-hour urinary protein quantitative
      determination and urinary albumin excretion rate (UAER) were analyzed to evaluate
      early organ damage. Left ventricular hypertrophy was defined as LVMI > 125 g/m(2)
      in men and > 120 g/m(2) in women, and UAER between 20 ug/min and 200 ug/min was
      defined as microalbuminuria. RESULTS: vWF [(122.3 +/- 53.8)% vs. (113.1 +/-
      68.3)%], sICAM-1 [(401.0 +/- 74.1) ug/L vs. (300.9 +/- 87.0) ug/L], ox-LDL [(13.6
      +/- 10.0) U/L vs. (8.1 +/- 5.9) U/L], LVMI [(124.7 +/- 33.6) g/m(2) vs. (109.1 +/
      25.7) g/m(2)], 24-hour urinary protein quantitation [24 h UPQ, (0.17 +/- 0.10) g
      vs. (0.09 +/- 0.04) g] and UAER [(25.9 +/- 7.7) ug/min vs. (9.7 +/- 5.9) ug/min]
      were significantly higher in PA group than in EH group (all P < 0.05). Elevated
      plasma vWF, sICAM-1 levels and plasma aldosterone concentration independently
      predicted microalbuminuria. Whereas, elevated plasma vWF and ox-LDL levels,
      plasma aldosterone concentration and systolic blood pressure independently
      predicted left ventricular hypertrophy. CONCLUSION: Patients with PA have severer
      endothelial dysfunction reflected by multiple biomarkers and earlier organ damage
      than patients with EH, and plasma aldosterone concentration and multiple
      endothelial dysfunction biomarkers could independently predict early organ
      damage.

PMID- 23141007
TI  - [History of pregnancy induced hypertension is linked with increased risk of
      cardio-cerebral vascular events].
AB  - OBJECTIVE: To compare the incidence of cardio-cerebral vascular events between
      pregnancy induced hypertension (PIH) women and non-PIH(NPIH) women. METHODS:
      Ambispective cohort study method was used and 4630 pregnant women giving birth
      during October 1976 to December 2008 in our hospital and participated the healthy
      examination between July 2006 and October 2007 at Kailuan medical group were
      included and divided into PIH group (n = 694) and NPIH group (n = 3936) by the
      history of PIH. Incidence of cardio-cerebral vascular events (myocardial
      infarction, cerebral infarction and cerebral hemorrhage) was obtained during
      follow-up. Multivariable Cox proportional hazards regression models was used to
      assess the relative risk of cardio-cerebral vascular events. RESULTS: (1) The
      follow-up time was 2 to 34 (15.32 +/- 7.94) years. (2) The childbearing age,
      systolic blood pressure and diastolic blood pressure before delivery were
      significantly higher while gestational weeks and weight of newborn were
      significantly less in PIH group than in NPIH group (all P < 0.01). Levels of
      systolic blood pressure, diastolic blood pressure, waist circumference, body mass
      index, triglyceride, total cholesterol and fasting blood glucose during healthy
      examination between July 2006 and October 2007 were significantly higher in PIH
      group than in NPIH group (P < 0.05 or P < 0.01). (3) There were 71 cardio
      cerebral vascular events during the follow-up. In PIH group, the incidence rate
      of cardio-cerebral vascular events, myocardial infarction and cerebral infarction
      was 20.64%, 11.08% and 8.67%, respectively, while the corresponding incidence
      rate was 7.82%, 4.02% and 2.67% in NPIH group (all P < 0.01). After adjustment
      for other traditional cardiovascular risk factors, the risk of total cardio
      cerebral vascular events, myocardial infarction and cerebral infarction in PIH
      group was 2.99 fold (95%CI: 1.80 - 4.95), 3.91 fold (95%CI: 1.71 - 8.91) and 3.96
      fold (95%CI: 1.95 - 8.05) higher than in NPIH group. CONCLUSION: PIH is an
      independent risk factor for cardio-cerebral vascular events.

PMID- 23141008
TI  - [Clinical characteristics of 161 Chinese patients with idiopathic pulmonary
      arterial hypertension].
AB  - OBJECTIVE: To investigate the clinical characteristics of patients with
      idiopathic pulmonary arterial hypertension (IPAH) in China. METHODS: A total of
      161 patients diagnosed as IPAH in Shanghai Pulmonary Hospital from June 2008 to
      June 2010 were retrospective analyzed. RESULTS: The mean diagnostic age was (33
      +/- 15) years old and 70.2% patients were female. The median duration from
      symptoms onset to diagnostic right heart catheterization was 12 months. Incidence
      of NYHA class III to IV was 56.5% at diagnosis and the mean six minutes walk
      distance was limited to (398 +/- 108) meters. Incidence of mild obstructive,
      restrictive and diffusing impairment in pulmonary function test was 7.8%, 42.2%
      and 82.2% patients with IPAH, respectively. Right heart catheterization
      demonstrated severe elevated mean pulmonary arterial pressure [(63 +/- 17) mm Hg
      (1 mm Hg = 0.133 kPa)] and pulmonary vascular resistance index [(25 +/- 12) Wood
      U/m(2)] in this patient cohort. The response rate of acute pulmonary
      vasoreactivity testing was 8.7% in this cohort. Compared with non-responders,
      responders to acute pulmonary vasoreactivity testing were younger and with less
      severe pulmonary hypertension. Among non-responders, 89% patients were treated by
      one specific anti-pulmonary arterial hypertension drug and 27% patients received
      combined anti-pulmonary arterial hypertension medications. CONCLUSIONS: Young
      female was predominantly involved in patients with IPAH in China. The diagnosis
      of IPAH is often made at advanced disease stage and majority patients with IPAH
      received specific anti-pulmonary arterial hypertension therapies in this patient
      cohort.

PMID- 23141009
TI  - [Clinical analysis of 150 patients with idiopathic pulmonary arterial
      hypertension].
AB  - OBJECTIVE: To explore the demographic characteristics and clinical features of
      patients with idiopathic pulmonary arterial hypertension (IPAH) in China.
      METHODS: Between March 2007 and September 2010, IPAH diagnosis was confirmed by
      right heart catheterization in 150 adult patients from 31 clinical centers in
      China. Clinical and hemodynamic data were analyzed and patients were divided into
      WHO functional class I/II and WHO functional class III/IV group. RESULTS: The
      mean age of 150 patients were 36 +/- 13 years with female patient/male patient
      ratio of 2:1, and mean BMI was (21.3 +/- 3.5) kg/m(2). Fatigue (n = 123, 82.0%)
      and dyspnea (n = 112, 74.7%) are the most common symptoms. Accentuated pulmonic
      second sound (P(2)) was detected in 92.0% (n = 138) of patients during physical
      examination, which was also the most common sign. About 49.0% (n = 73) patients
      were WHO functional class I/II patients and 46.0% (n = 68) patients were WHO
      functional class III/IV patients. Six minutes walking distance (6MWD) and Borg
      dyspnea score was (337 +/- 101) m and 2.0 (2.0, 4.0), respectively. Right
      ventricular hypertrophy was suggested by ECG in 93.1% (n = 140) patients. Right
      atrial pressure was (10 +/- 6) mm Hg, mean pulmonary artery pressure was (61 +/-
      16) mm Hg, cardiac index was (2.3 +/- 0.8) L*min(-1)*m(-2) and pulmonary vascular
      resistance (1484 +/- 699) dyn*s(-1)*cm(-5) in this cohort. 6 MWD (305 m +/- 89 m
      vs. 377 m +/- 88 m) was significantly shorter while Borg dyspnea score [3.0 (3.0,
      5.0) vs. 2.0 (2.0, 3.0)] was significantly higher in WHO functional class III/IV
      patients than in WHO functional class I/II patients. Similarly hemodynamic
      parameters were also worse in WHO functional class III/IV patients than in WHO
      functional class I/II patients (all P < 0.05). CONCLUSION: Idiopathic pulmonary
      arterial hypertension patients in this cohort affect mostly young adults,
      dominated by female gender and lower body mass index. Fatigue and dyspnea are the
      most common symptoms and accentuated pulmonic second sound (P(2)) is the most
      common sign. IPAH patients are often displaying severe functional and hemodynamic
      disturbance at first visit to hospitals. Dyspnea and hemodynamic impairment are
      related to 6MWD and WHO functional class.

PMID- 23141010
TI  - [Clinical application of VerifyNow-P2Y12 assay in evaluation of platelet
      inhibition efficacy of clopidogrel].
AB  - OBJECTIVE: To evaluate the platelet inhibition efficacy in patients under regular
      maintenance dose of clopidogrel by VerifyNow-P2Y12 assay and explore the clinical
      characteristics of clopidogrel non-responders and related predicting factors.
      METHODS: A total of 99 patients underwent percutaneous coronary intervention
      procedure and receiving clopidogrel in regular maintenance dose for at least 1
      week were enrolled. Platelet reactivity, including baseline, P2Y12 reaction unit
      (PRU), and platelet inhibition rate were measured with VeifyNow-P2Y12 assay. The
      dosage of anti-platelet drugs, combination with any other drugs, clinical
      characters in baseline of all enrolled patients were analyzed. PRU <= 240 was
      used as cut-off to identify clopidogrel responder and clopidogrel non-responder.
      In the non-responder group, patients were further separated into 3 sub-groups
      (types) according to the baseline and platelet inhibition rate: type I with high
      baseline, high inhibition rate, representing false non-responder; type II with
      low inhibition rate, representing true non-responder and type III mixed type.
      RESULTS: In this study, 48 of 99 patients were found to be clopidogrel non
      responder (48.5%). The ratio of type I, type II and type III in the non-responder
      group was 9.1% (n = 9), 27.3% (n = 27), and 12.1% (n = 12), respectively.
      Baseline platelet value in female patients was significantly higher than in males
      (P < 0.01), number of females with high PRU also is higher than males (P < 0.01),
      female gender was a predict factor for type I non-responder (OR = 6.5, 95%CI
      2.295 - 18.407, P < 0.01). BMI > 24 kg/m(2) was a risk factor for clopidogrel non
      responder (P < 0.05), and may be regarded as a predict factor for type II non
      responder (OR = 3.207, 95%CI 1.375 - 7.485, P < 0.01). Age, hypertension,
      diabetics, smoking, hyperlipidemia, CRP and pantoprazole use do not show
      significant correlation with baseline and platelet inhibition rate. CONCLUSIONS:
      Clopidogrel responses could be reliably detected by VerifyNow-P2Y12 assay. Female
      gender and high body weight are independent risk factors for clopidogrel non
      responses.

PMID- 23141011
TI  - [Association between left ventricular twist/untwist and diastolic dysfunction of
      high cardiovascular risk population in the community].
AB  - OBJECTIVE: To assess the association between left ventricular (LV) twist and
      untwist with the severity of diastolic dysfunction of high cardiovascular risk
      population in the community. METHODS: This cross-sectional survey was performed
      in high cardiovascular risk people with normal left ventricular (LV) ejection
      fraction in an urban community of Beijing (n = 620). Normal LV diastolic function
      was defined in 305 subjects, mild diastolic dysfunction in 266 subjects and
      moderate/severe diastolic dysfunction in 49 subjects. Peak LV twist, peak twist
      velocity, peak untwist velocity and untwist rate were measured in apical and
      basal short-axis images using speckle tracking echocardiography. RESULTS: Peak LV
      twist was similar among subjects with normal diastolic function, mild diastolic
      dysfunction and moderate/severe diastolic dysfunction. Peak twist velocity
      [(129.3 +/- 45.3) degrees /s vs. (118.0 +/- 36.2) degrees /s] and untwist
      velocity [(-132.9 +/- 50.4)  degrees /s vs. (-121.2 +/- 41.4) degrees /s] were
      significantly higher in mild diastolic dysfunction group than in normal diastolic
      function group (all P < 0.01) and similar between normal diastolic function and
      moderate/severe diastolic dysfunction group (P > 0.05). Untwist rate of
      moderate/severe diastolic dysfunction decreased significantly than that of normal
      diastolic function [(41.9 +/- 32.9) degrees /s vs. (57.7 +/- 36.2)  degrees /s, P
      < 0.01] and mild diastolic dysfunction group [(41.9 +/- 32.9) degrees /s vs.
      (60.9 +/- 39.9)  degrees /s, P < 0.01]. CONCLUSIONS: Twist and untwist parameters
      are increased/preserved in population with normal systolic function and mild
      diastolic dysfunction and "normalized" or reduced in those with advanced
      diastolic dysfunction. The maintaining (if not increasing) of LV twist in early
      diastolic dysfunction might serve as a compensatory mechanism in case of reduced
      myocardial relaxation in these subjects.

PMID- 23141012
TI  - [Evaluation of the association between left coronary artery stenosis degree and
      myocardial perfusion by 64 multi-slice].
AB  - OBJECTIVE: To evaluate the association between left coronary artery stenosis
      degree and myocardial perfusion by 64 multi-slice CT. METHODS: A total of 223
      patients underwent 64 multi-slice CT coronary artery images (CTA) were included
      and divided into normal group (91 cases), mild stenosis group (72 cases),
      moderate stenosis group (36 cases) and severe stenosis group (24 cases).
      Myocardial density was measured at apical, septal and lateral segments.
      Myocardial density in infarcted segments was compared to non-infarct segments in
      11 patients with old myocardial infarction (all from severe stenosis group).
      RESULTS: Myocardial density was significantly lower at apical segments [(55.8 +/-
      21.4) HU vs. (75.3 +/- 7.5) HU], at septal segment [(87.8 +/- 3.3) HU vs. (98.2
      +/- 5.2) HU] and at lateral segment [(86.8 +/- 7.9) HU vs. (95.6 +/- 11.6) HU] in
      severe stenosis group than in normal group (all P < 0.05). Myocardial density of
      patients with old myocardial infarction was significantly reduced in non-infarct
      segment [(70.9 +/- 8.3) HU vs.(98.7 +/- 7.3) HU, P < 0.01] and increased in
      infarct segment [(42.5 +/- 15.7) HU vs. (17.8 +/- 4.1) HU, P < 0.01] post
      contrast enhancement. CONCLUSION: CTA could be used to evaluate the severity of
      the left coronary artery stenosis based on myocardial density measurement.
      Myocardial delayed enhancement derived from CTA could be used to identify infarct
      segments.

PMID- 23141013
TI  - [Efficacy comparison between total aortic arch reconstruction with open placement
      of triple-branched stent graft and total aortic replacement combined with stented
      elephant trunk implantation for patients with Stanford A aortic dissection].
AB  - OBJECTIVE: To compare the clinical efficacy between total aortic arch
      reconstruction with open triple-branched stent graft placement and total aortic
      replacement combined with stented elephant trunk implantation for patients with
      Stanford A aortic dissection. METHODS: Patients with Stanford A aortic dissection
      treated with surgical treatment from January 2006 to May 2011 were included in
      this study. The patients were divided into two groups. Group I (n = 20) patients
      were treated by total arch replacement with stented elephant trunk procedure.
      Group II (n = 8) patients received open triple-branched stent graft placement.
      Echocardiography and aortic CT angiography were performed before and at 1 month
      after operation. RESULTS: Age, gender and disease severity were similar between
      the 2 groups (all P > 0.05). Operation was successful in all 28 patients.
      Cardiopulmonary bypass time, aortic cross clamp time, circulation arrest time and
      duration of ventilator assisted breathing were significantly longer;
      postoperative drainage volume and blood transfusion volume were significantly
      larger and hospitalization cost was significantly higher in group I patients
      compared those in group II patients (all P < 0.05). One month after operation,
      the maximum internal diameter of aorta was smaller than pre-operation in both
      group I [(30.2 +/- 3.1) mm vs. (42.5 +/- 6.5) mm, P < 0.05] and group II [(31.5
      +/- 2.5) mm vs. (44.1 +/- 7.3) mm, P < 0.05]. CONCLUSIONS: Short-term procedural
      success rate was similar between the two groups. The total aortic arch
      reconstruction with open triple-branched stent graft placement procedure is
      simpler, shortens the operation time, reduces the blood transfusion volume and is
      more cost-effective compared to the classical aortic arch operation.

PMID- 23141014
TI  - [Efficacy of hybrid balloon valvuloplasty via sternotomy for treating low-body
      weight infants with severe congenital valvular aortic stenosis].
AB  - OBJECTIVE: To observe the efficacy of hybrid balloon valvuloplasty for the
      treatment of low-body weight infants with severe congenital valvular aortic
      stenosis (AS). METHODS: Five infants with severe congenital valvular aortic
      stenosis underwent the hybrid balloon aortic valvuloplasty through median
      sternotomy in the hybrid operating room. The mean age was (40.2 +/- 7.0) days,
      weight was (4.48 +/- 0.75) kg. The patients were followed up by echocardiography
      for 9 - 13 months post procedure. RESULTS: Operation was successful in all 5
      patients and they were discharged from hospital uneventfully. The gradient
      pressure decreased significantly from (98.8 +/- 9.0) mm Hg (1 mm Hg = 0.133 kPa)
      to (13.8 +/- 3.3) mm Hg (P < 0.05) post operation. There was no moderate or
      severe aortic insufficiency. All patients were alive, the gradient pressures was
      (18.8 +/- 2.5) mm Hg and there was no moderate or severe aortic insufficiency
      during follow-up [9 - 13 (11.0 +/- 1.4) months]. CONCLUSION: The hybrid balloon
      aortic valvuloplasty is an effective option for the low-body weight infants with
      severe congenital valvular aortic stenosis.

PMID- 23141015
TI  - [Nuclear factor kappaB and IKB expression and calcium deposition of
      atherosclerotic plaques in apolipoprotein E and low density lipoprotein receptor
      knockout mice].
AB  - OBJECTIVE: To observe the histopathological features, nuclear factor-kappaB
      (NFkappaB) and IKB expressions as well as calcium deposition of atherosclerosis
      plaques (AS) in apolipoprotein E (ApoE) and low density lipoprotein receptor
      (LDLR) knockout mice (ApoE(-/-), LDLR(-/-)fed high-fat diet. METHODS: Eight
      C57BL/6J mice fed with normal diet were used as control, 32 ApoE(-/-) mice and
      LDLR(-/-) mice were divided into normal diet and high-fat diet groups (n = 8
      each). After 4 months, aorta was collected for morphologic (HE, Oil Red O, Von
      Kossa) and immunohistochemistry (nuclear factor-kappaB, IKB, macrophage surface
      molecule-3, alpha-smooth action protein) analysis. RESULTS: Degree of AS in ApoE(
      /-) and LDLR(-/-) mice fed with high-fat diet were significantly severer than
      those fed with normal diet and AS was more significant in ApoE(-/-) mice than in
      LDLR(-/-) mice. NFkappaB and IKB expressions in high-fat diet group were
      significantly higher than the normal diet group (P < 0.05). Double-labeling of
      NFkappaB revealed dominant expression in smooth muscle cells. Calcium deposition
      was significantly more in ApoE(-/-) mice fed with high-fat diet than mice fed
      with normal diet (P < 0.05) and was similar in LDLR(-/-) mice fed with high and
      normal diet (P > 0.05). CONCLUSION: High-fat diet contributes to the formation of
      AS plagues in ApoE(-/-) and LDLR(-/-) mice joined by upregulated NFkappaB and IKB
      expressions and calcium deposition.

PMID- 23141016
TI  - [Establishment of human cardiac C protein induced experimental autoimmune
      myocarditis model in rat].
AB  - OBJECTIVE: To construct the recombinant plasmid of human cardiac C protein (CCP)
      peptide with immunogenicity and to express, purification and renature fusion
      protein. The fusion protein was injected to Lewis rats to establish experimental
      autoimmune myocarditis (EAM) model. METHODS: Total RNA was extracted from human
      heart and used as the template for reverse transcriptase-directed cDNA synthesis.
      The cDNA was then amplified by polymerase chain reaction (PCR) using
      oligonucleotide primers specific for CCP peptide with immunogenicity.
      Subsequently, the purified CCP peptide gene was cloned into PEASY-T1 vector and
      the ligated product was identified by PCR and DNA sequence analysis. Then the CCP
      target gene of positive clone was inserted into the pQE30, a prokaryotic
      expression vector, and the inserting plasmid was transformed into Escherichia
      coli. host M15. The positive clone extracted from the bacterium liquid was sieved
      by insertional inactivation sieve method and identified by PCR of bacterium
      liquid, CCP immunological peptide was purified and renatured in semipermeable
      membrane. EAM model in Lewis rats was induced by injection of mixture of 100 ug
      CCP fusion protein immunological peptide and 2.5 g/L completed Freund adjuvant
      from two double foot pad and subsequent abdominal injection of 0.5 ug pertussis
      toxin. Two, four, six, and eight weeks after immunization, hemodynamic evaluation
      was made and hearts underwent histological examination. RESULTS: The DNA sequence
      analysis for cloning vector extraction revealed that the CCP target gene was
      cloned into pQE30 exactly. The DNA of 1000 bp length was obtained by PCR
      examination of bacterium liquid with transformation of express recombinants which
      were consistent with the expected size. Purified fusion protein in vertical slab
      gel electrophoresis showed 35 000 as expected. The recombinant CCP fusion protein
      existed in inclusion bodies of E. coli and amounted to 80% - 90% of the total
      protein. Hemodynamic and histological evaluations showed typical acute
      inflammatory responses at 2 weeks, subacute inflammatory and fibrosis changes at
      4 weeks after injection, and signs of chronic dilated cardiomyopathy at 6 weeks
      post injection. CONCLUSION: Combination of gene clone technique and histidine tag
      protein purification technique can be used to synthesize human cardiac C protein
      to induce EAM model in Lewis rat.

PMID- 23141017
TI  - [Effects of valsartan on aortic angiotensin converting enzyme 2 expression after
      aortic balloon injury in rats].
AB  - OBJECTIVE: To investigate the process and mechanism of neointimal formation, the
      level of angiotensin II and angiotensin (1-7), the expression of angiotensin
      converting enzyme 2(ACE2), angiotensin II type 1 receptor (AT(1)R), extracellular
      signal regulated kinase (ERK) and the effects of valsartan on them after aortic
      balloon injury in rats. METHODS: Aortic endothelial denudation of rats was
      induced by 2F balloon catheter. Thirty-six rats were randomly allocated into
      three groups: Group 1 (n = 12): controls; Group 2 (n = 12): aortic balloon
      injury; Group 3 (n = 12): valsartan (20 mg*kg(-1)*d(-1)) given from 1 day before
      injury to 14 and 28 days after aortic injury. The expression of ACE2 and AT1, the
      level of P-ERK, AngII, Ang(1-7) and intimal thickening were investigated by RT
      PCR technique, immunohistochemistry, Western blot, radioimmunological method,
      enzyme linked immunosorbent assay (ELISA) and HE stain, respectively. RESULTS:
      (1) The proliferation of vascular smooth muscle cells (VSMC) and the intimal
      thickening were evidenced at day 14 and 28 after aortic balloon injury. (2) The
      mRNA and protein expressions of ACE2 decreased significantly, but AT(1)R mRNA and
      protein expression increased significantly at day 14 and 28 after balloon injury.
      (3) The level of AngII and p-ERK increased and Ang(1-7) reduced after balloon
      injury. (4) Valsartan not only attenuated the proliferation of VSMC and the
      intimal thickening but also upregulated the expression of ACE2 and the level of
      Ang(1-7) and downregulated the expression of AT(1)R and the level of AngII, p-ERK
      in this model. CONCLUSION: Intimal thickening after balloon injury is linked with
      reduced expression of ACE2.Valsartan can inhibit the intimal thickening possibly
      by upregulating ACE2 and Ang(1-7) and downregulating AT(1) in this model.

PMID- 23141018
TI  - [Assessment of the right ventricular function in healthy volunteers with one beat
      full-volume real-time three-dimensional echocardiography].
AB  - OBJECTIVE: To determine the normal value of right ventricle using one beat full
      volume real-time three-dimensional echocardiography (RT-3DE) and assess the
      feasibility of this technique. METHODS: One beat full volume images were acquired
      at the apical 4 chamber view in 129 healthy volunteers. The right and left
      ventricular volumes were examined with the eSie LVA and RVA. The subjects were
      divided into 2 gender groups (male and female) and 3 age groups (20 - 39 years
      old, 40 - 59 years old, 60 years old and above). RESULTS: Adequate data were
      obtained in 129 subjects. The RV-EDV was (92.4 +/- 21.3) ml, RV-ESV (34.6 +/-
      9.2) ml, RV-SV (57.8 +/- 13.9) ml, RV-EF (62.5 +/- 5.0) ml. EDV, ESV, and EF were
      significant different while SV was similar between RV and LV (all P < 0.05). RV
      EDV (r = 0.517, P = 0.001), RV-ESV (r = 0.588, P = 0.001) and RV-SV(r = 0.409, P
      = 0.001) were correlated well with BSA. RV-EDV, RV-ESV and RV-SV were
      significantly higher in males than in females (all P < 0.001). RV-EDV, RV-SV and
      RV-EF decreased with aging (P < 0.05). CONCLUSIONS: Right ventricle function can
      be measured noninvasively by RT-3DE with high feasibility. This novel method
      contributes to the detailed study of right heart function in various
      cardiovascular diseases.

PMID- 23141019
TI  - [Variant angina pectoris induced by left and right coronary artery spasm
      simultaneously or in turn].

PMID- 23141020
TI  - [A case of variant angina with wandering ST segment elevation from inferior leads
      to anterior leads].

PMID- 23141021
TI  - [One patient with hemochromatosis characterized by heart failure and ascites].

PMID- 23141022
TI  - [Autophagy and myocardial ischemia reperfusion injury].

PMID- 23141023
TI  - [Recent advances of studies on microRNA in platelet].

PMID- 23141024
TI  - Can the Gail model increase the predictive value of a positive mammogram in a
      European population screening setting? Results from a Spanish cohort.
AB  - AIMS OF THE STUDY: The Gail Model (GM) is the most well-known model to assess the
      individual risk of breast cancer (BC). Although its discriminatory accuracy is
      low in the clinical context, its usefulness in the screening setting is not well
      known. The aim of this study is to assess the utility of the GM in a European
      screening program. METHODS: Retrospective cohort study of 2200 reassessed women
      with information on the GM available in a BC screening program in Barcelona,
      Spain. The 5 year-risk of BC applying the GM right after the screening mammogram
      was compared first with the actual woman's risk of BC in the same screening round
      and second with the BC risk during the next 5 years. RESULTS: The curves of BC
      Gail risk overlapped for women with and without BC, both in the same screening
      episode as well as 5 years afterward. Overall sensitivity and specificity in the
      same screening episode were 22.3 and 86.5%, respectively, and 46.2 and 72.1% 5
      years afterward. ROC curves were barely over the diagonal and the concordance
      statistics were 0.59 and 0.61, respectively. CONCLUSION: The GM has very low
      accuracy among women with a positive mammogram result, predicting BC both in the
      concomitant episode and 5 years later. Our results do not encourage the use of
      the GM in the screening context to aid the referral decision or the type of
      procedures after a positive mammogram or to identify women at high risk among
      those with a false-positive outcome.

PMID- 23141025
TI  - Swapping or dropping? Electrophysiological measures of difficulty during multiple
      object tracking.
AB  - In the multiple object tracking task, participants are asked to keep targets
      separate from identical distractors as all items move randomly. It is well known
      that simple manipulations such as object speed and number of distractors
      dramatically alter the number of targets that are successfully tracked, but very
      little is known about what causes this variation in performance. One possibility
      is that participants tend to lose track of objects (dropping) more frequently
      under these conditions. Another is that the tendency to confuse a target with a
      distractor increases (swapping). These two mechanisms have very different
      implications for the attentional architecture underlying tracking. However,
      behavioral data alone cannot differentiate between these possibilities. In the
      current study, we used an electrophysiological marker of the number of items
      being actively tracked to assess which type of errors tended to occur during
      speed and distractor load manipulations. Our neural measures suggest that
      increased distractor load led to an increased likelihood of confusing targets
      with distractors while increased speed led to an increased chance of a target
      item being dropped. Behavioral experiments designed to test this novel prediction
      support this assertion.

PMID- 23141026
TI  - Gender differences among older drivers in a comprehensive driving evaluation.
AB  - Research studies typically consider older drivers as a homogenous group and do
      not report on the influence of gender on driving performance. Prior studies
      report that females are over-represented in crashes compared to males, caused by
      errors of yielding, gap acceptance, and speed regulation, all of which are
      assessed in a comprehensive driving evaluation (CDE). In a sample of 294
      community dwelling older drivers, we examined and compared specific and total
      driving errors of both genders, and determined predictors of gender-specific
      driving errors and pass/fail outcomes who completed a CDE assessed by a certified
      driving rehabilitation specialist. No differences in specific or total number of
      driving errors on the CDE were found between older males (Mean age 73.4+/-6.0)
      and older females (Mean age 73.8+/-5.7). Education, days of driving, Useful Field
      of ViewTM (UFOV), Rapid Paced Walk Test (RPW) and the Mini-Mental State Exam
      (MMSE) were all independent predictors of failing a road test for both genders
      (p<0.05). However, older females were 22% less likely than older males to fail an
      on-road test. Within group comparisons showed that older males and females >75
      years were 3.2 and 3.5 times more likely to fail the on-road test compared to
      younger males and females (aged between 63 and 75), respectively. Our findings
      suggest that focusing on older old (75+) and old-old (85+) age groups may be more
      efficient for future investigations of driving performance. 

PMID- 23141028
TI  - Clinical features of suicide attempts in adults with autism spectrum disorders.
AB  - OBJECTIVE: The objective of this study was to investigate the frequency and
      clinical features of suicide attempts in adults with autism spectrum disorders
      (ASDs). METHODS: We enrolled 587 consecutive patients aged 18 or over who
      attempted suicide and were hospitalized for inpatient treatment. Psychiatric
      diagnoses, suicide attempt frequency and clinical features were compared between
      ASD and non-ASD patients. RESULTS: Forty-three (7.3%) of the 587 subjects who
      attempted suicide had ASDs. The incidence of patients with mood disorders was
      significantly lower (Fisher's Exact Test, P=.043) and that of those with an
      adjustment disorder was significantly higher (Fisher's Exact Test, P<.001) in the
      ASD group than in the non-ASD group. The average length of stay at both the
      hospital and intensive care unit in the ASD group was longer than that in the non
      ASD group (z=-2.031, P=.042; z=-2.322, P=.020, respectively). CONCLUSIONS: ASDs
      should always be a consideration when dealing with suicide attempts in adults at
      the emergency room.

PMID- 23141027
TI  - Depression treatment preferences of older white and Mexican origin men.
AB  - OBJECTIVE: Among older white and Mexican origin male primary care patients, we
      examined preferences for features of depression care programs that would
      encourage depressed older men to enter and remain in treatment. METHOD: Sixty
      three (45 white, 18 Mexican origin) older men were recruited in six primary care
      clinics. All had clinical depression in the past year and/or were receiving
      depression treatment. Participants completed a conjoint analysis preference
      survey regarding depression treatments, providers and treatment enhancements.
      RESULTS: The data suggest that white men preferred medication over counseling
      [odds ratio (OR): 1.64 95% confidence interval (CI): 1.12-2.41], while Mexican
      origin men preferred counseling (OR: medication over counseling: 0.28, 95% CI:
      0.12-0.66). Both white and Mexican origin men preferred treatment that included
      family involvement (vs. none) (white: OR: 1.60, 95% CI 1.12-2.30; Mexican origin:
      OR: 3.31 95% CI 1.44-7.62) and treatment for insomnia (vs. treatment for alcohol
      use) (white: OR: 1.72, 95% CI 1.01-2.91; Mexican origin: OR: 3.93 95% CI 1.35
      11.42). White men also preferred treatment by telephone (OR: 1.80, 95% CI 1.12
      2.87). CONCLUSIONS: Findings could inform development of patient-centered
      depression treatment programs for older men and suggest strategies, such as
      attention to sleep problems, which providers may employ to tailor treatment to
      preferences of older men.

PMID- 23141029
TI  - Gender-specific predictors of risky alcohol use among general hospital
      inpatients.
AB  - OBJECTIVE: To investigate sociodemographic-, living situation- and substance
      related variables as predictors of current risky alcohol use for both female and
      male general hospital inpatients. METHOD: The sample of 6050 female and 8282 male
      general hospital inpatients was recruited in 2002-2004. Using the Alcohol Use
      Disorder Identification Test-Consumption, they were assigned to four drinking
      groups: abstinent, moderate use, slightly increased use and notably increased
      use. Gender-specific predictors of group affiliation were determined using
      multivariate multinomial logistic regressions. RESULTS: In both genders, younger
      age, rural living environment, the occurrence of lifetime alcohol use disorders
      (AUDs) and current tobacco smoking were positively associated with risky alcohol
      use. Higher education was positively associated with slightly and notably
      increased use for women. Living alone, being divorced/ widowed and being
      unemployed (relative risk ratios=1.4-1.7) were positively associated with notably
      increased use for men. In both genders, older age, less education and the
      occurrence of lifetime AUDs were positively associated with abstinence.
      CONCLUSIONS: Higher educated women are likely to report risky alcohol use.
      Marriage may have a protective effect on level of alcohol use for men only. In
      addition to the implementation of routine alcohol screening, the examined data
      may provide cost-effective information that could be used to tailor
      interventions.

PMID- 23141030
TI  - Impact of antimicrobial therapy on prognosis of patients requiring valve surgery
      during active infective endocarditis.
AB  - OBJECTIVES: We examined the characteristics and outcomes of patients requiring
      valve surgery during active infective endocarditis (IE), focusing on the impact
      of antimicrobial therapy. METHODS: In this retrospective study, medical charts of
      all consecutive patients admitted to our cardiovascular surgery department from
      January 1998 to December 2010, with a diagnosis of IE requiring surgical
      management, were reviewed. Adult patients were enrolled in the study if they had
      definite or possible active IE and if the antimicrobial treatment was evaluable.
      RESULTS: After initial screening of medical records, we selected 173 surgically
      treated patients (135 men; mean age, 55.8 years). Native valves were involved in
      150 (87%) patients. IE mainly involved the aortic valve (n = 113) and then mitral
      (n = 83), tricuspid (n = 13), and pulmonary (n = 3) valves. The most common
      causative pathogens were streptococci (n = 70), staphylococci (n = 60), and
      enterococci (n = 29). Operative mortality was 15%. Multivariate logistic
      regression analysis demonstrated that adequacy of the overall antimicrobial
      treatment (adjusted odds ratio, 0.292; 95% confidence interval, 0.117-0.726; P =
      .008) and temperature greater than 38 degrees C at the time of diagnosis
      (adjusted odds ratio, 0.288; 95% confidence interval, 0.115-0.724; P = .008) were
      independently associated with a lower risk of mortality. Conversely, age greater
      than 60 years (adjusted odds ratio, 4.42; 95% confidence interval, 1.57-12.4; P =
      .005) was associated with a greater risk of operative mortality. CONCLUSIONS:
      Surgery for active IE is still associated with a high mortality rate, but its
      prognosis is significantly improved by adequate antimicrobial therapy.

PMID- 23141031
TI  - Clinical validation of coronary artery flow through an intracoronary shunt during
      off-pump coronary artery bypass grafting.
AB  - OBJECTIVES: Intracoronary shunts have been developed for a bloodless field and
      preserved forward flow preventing ischemia during off-pump coronary artery bypass
      (OPCAB) surgery. However, reports directly measuring the forward flow through the
      shunt in clinical settings are lacking. METHODS: Using a 7.5-MHz Doppler probe,
      we investigated the coronary flow through a 1.5-mm shunt inserted into the left
      anterior descending artery (LAD) for anastomosis with the internal thoracic
      artery during OPCAB in 30 consecutive patients. The following Doppler flow
      parameters were obtained before and after shunting: peak velocity, mean velocity,
      time-velocity integral, and flow. RESULTS: No patients developed significant
      electrocardiographic changes and the peak value of postoperative myocardial band
      of creatine kinase was 17 +/- 16 IU/L. All Doppler flow parameters of the LAD
      decreased significantly after shunting; peal velocity: 71.3 +/- 34.6 cm/second to
      54.5 +/- 25.3 cm/second (-24% +/- 27%), mean velocity: 33.3 +/- 18.3 cm/second to
      26.3 +/- 14.0 cm/second (-21% +/- 23%), and time-velocity integral: 28.7 +/- 12.1
      cm to 19.0 +/- 7.1 cm (-28% +/- 14%), and flow: 38.7 +/- 16.8 mL/minute to 25.0
      +/- 9.5 mL/minute (-31% +/- 13%) (P < .01). CONCLUSIONS: The LAD flow is
      preserved at least 50% through a 1.5-mm intracoronary shunt, although the flow
      pattern was attenuated, during OPCAB anastomosis. The Doppler evaluation of the
      coronary artery flow before and after shunting is useful to justify the
      protective use of the shunt on myocardial perfusion during OPCAB.

PMID- 23141032
TI  - The impact of temperature and pump flow rate during selective cerebral perfusion
      on regional blood flow in piglets.
AB  - OBJECTIVE: Ideal temperature and flow rate for selective cerebral perfusion (SCP)
      are not known. We examined regional organ perfusion in a piglet SCP model.
      METHODS: Three groups underwent SCP at 30 mL/kg/min at different temperatures (15
      degrees C, 25 degrees C, and 32 degrees C) and 4 groups remained at 25 degrees C
      for SCP at different flow rates (10, 30, 50 and 75 mL/kg/min). Fluorescent
      microspheres were injected at 5 minutes of normothermic cardiopulmonary bypass
      (CPB), immediately before SCP, SCP 45 minutes, SCP 90 minutes, and 2 hours after
      CPB. Brain and lower body organs were collected to examine regional blood flow
      (RBF, mL/min/g). RESULTS: At 2 hours after CPB, RBF of the 32 degrees C group was
      higher than that of the 15 degrees C group (P < .05) at the caudate nucleus and
      hippocampus; RBF of the 32 degrees C group was higher than that of the 25 degrees
      C and 15 degrees C groups (P < .05) at the neocortex. No significant difference
      in RBF was observed among any of the 25 degrees C groups at different flow rates.
      Also, there was no significant difference between the RBF to the left and right
      sides of brain in either the temperature or flow rate groups. RBF did
      significantly increase with temperature in the liver and quadriceps during SCP (P
      < .05). At the kidney, RBF at SCP 90 minutes was significantly higher than that
      at SCP 45 minutes when all temperature groups were combined (P < .05).
      CONCLUSIONS: SCP at 32 degrees C provides higher brain RBF 2 hours after CPB.
      Increasing SCP flow rate does not increase RBF significantly at 25 degrees C.
      Higher temperature during SCP results in improved RBF to the liver and
      quadriceps.

PMID- 23141033
TI  - Aortic root thrombosis after transhiatal esophagectomy: a case report.

PMID- 23141034
TI  - Pulmonary resections performed at hospitals with thoracic surgery residency
      programs have superior outcomes.
AB  - OBJECTIVE: Pulmonary resections are performed at thoracic residency (TR), general
      surgery residency (GSR), no surgery residency, and no residency hospitals. We
      hypothesize that morbidity and mortality for these procedures are different
      between hospitals and that operations performed at TR teaching hospitals have
      superior results. METHODS: Records of adults who underwent pneumonectomy, lobar,
      segmentectomy, and nonanatomic wedge resections (N = 498,099) were evaluated in
      an all-payer inpatient database between 2003 and 2009. Hospital teaching status
      was determined by linkage to Association of American Medical College's Graduate
      Medical Education Tracking System. Multiple hierarchical regression models
      examined the in-hospital mortality, occurrence of any complication, and failure
      to rescue. RESULTS: The mean annual pulmonary resection volume among hospitals
      was TR (16%), GSR (17%), no surgery residency (28%), and no residency (39%).
      Unadjusted mortality for all procedures was lowest at TR hospitals (P < .001).
      Likewise, any complication was least likely to occur at TR hospitals (P < .001).
      After case-mix adjustment, the risk of any complication after segmentectomy or
      nonanatomic wedge resection was lower at TR hospitals than in GSR hospitals (P <
      .001). Among pneumonectomy recipients, TR hospitals reduced the adjusted odds
      ratio of failure to rescue by more than 25% compared with no surgery residency (P
      < .001). Likewise, in patients who underwent pneumonectomy, TR centers were
      associated with reducing the odds ratio of death by more than 30% compared with
      GSR hospitals (P < .001). CONCLUSIONS: In comparison with other hospitals,
      including GSR hospitals, TR hospitals have lower morbidity and mortality. These
      results support using hospitals with a TR as an independent prognostic indicator
      of outcomes in pulmonary resections.

PMID- 23141035
TI  - Historical perspectives of The American Association for Thoracic Surgery: Henry
      T. Bahnson (1920-2003).

PMID- 23141038
TI  - Factors affecting the social problem-solving ability of baccalaureate nursing
      students.
AB  - The hospital environment is characterized by time pressure, uncertain
      information, conflicting goals, high stakes, stress, and dynamic conditions.
      These demands mean there is a need for nurses with social problem-solving skills.
      This study set out to (1) investigate the social problem-solving ability of
      Chinese baccalaureate nursing students in Macao and (2) identify the association
      between communication skill, clinical interaction, interpersonal dysfunction, and
      social problem-solving ability. All nursing students were recruited in one public
      institute through the census method. The research design was exploratory, cross
      sectional, and quantitative. The study used the Chinese version of the Social
      Problem Solving Inventory short form (C-SPSI-R), Communication Ability Scale
      (CAS), Clinical Interactive Scale (CIS), and Interpersonal Dysfunction Checklist
      (IDC). Macao nursing students were more likely to use the two constructive or
      adaptive dimensions rather than the three dysfunctional dimensions of the C-SPSI
      R to solve their problems. Multiple linear regression analysis revealed that
      communication ability (beta=.305, p<.0001), clinical interaction (beta=.129,
      p=.047), and interpersonal dysfunction (beta=-.402, p<.0001) were associated with
      social problem-solving after controlling for covariates. Macao has had no problem
      solving training in its educational curriculum; an effective problem-solving
      training should be implemented as part of the curriculum. With so many changes in
      healthcare today, nurses must be good social problem-solvers in order to deliver
      holistic care. 

PMID- 23141040
TI  - Editorial comment.

PMID- 23141041
TI  - Commentary: Robotic radical prostatectomy is an effective approach for treating
      localized prostate cancer--is it technique or technician?

PMID- 23141042
TI  - Not getting lost in the gene-environment interaction exploration.

PMID- 23141043
TI  - 30Years of NPY research.

PMID- 23141044
TI  - [Genetics of the tobacco smoking].

PMID- 23141045
TI  - [Empyema by Actinomyces meyeri].

PMID- 23141046
TI  - [Troponins, a SOS signal in the failing heart].

PMID- 23141047
TI  - [Prognosis of death in end of life care: an elusive fact or a flawed paradigm?].

PMID- 23141048
TI  - Smoking and hand surgery.

PMID- 23141049
TI  - Final results of an EORTC-GU cancers group randomized study of maintenance
      bacillus Calmette-Guerin in intermediate- and high-risk Ta, T1 papillary
      carcinoma of the urinary bladder: one-third dose versus full dose and 1 year
      versus 3 years of maintenance.
AB  - BACKGROUND: The optimal dose and duration of intravesical bacillus Calmette
      Guerin (BCG) in the treatment of non-muscle-invasive bladder cancer (NMIBC) are
      controversial. OBJECTIVE: To determine if a one-third dose (1/3D) is not inferior
      to the full dose (FD), if 1 yr of maintenance is not inferior to 3 yr of
      maintenance, and if 1/3D and 1 yr of maintenance are associated with less
      toxicity. DESIGN, SETTING, AND PARTICIPANTS: After transurethral resection,
      intermediate- and high-risk NMIBC patients were randomized to one of four BCG
      groups: 1/3D-1 yr, 1/3D-3 yr, FD-1 yr, and FD-3 yr. OUTCOME MEASUREMENTS AND
      STATISTICAL ANALYSIS: The trial was designed as a noninferiority study with the
      null hypothesis of a 10% decrease in the disease-free rate at 5 yr. Times to
      events were estimated using cumulative incidence functions and compared using the
      Cox proportional hazards regression model. RESULTS AND LIMITATIONS: In an
      intention-to-treat analysis of 1355 patients with a median follow-up of 7.1 yr,
      there were no significant differences in toxicity between 1/3D and FD. The null
      hypotheses of inferiority of the disease-free interval for both 1/3D and 1 yr
      could not be rejected. We found that 1/3D-1 yr is suboptimal compared with FD-3
      yr (hazard ratio [HR]: 0.75; 95% confidence interval [CI], 0.59-0.94; p=0.01).
      Intermediate-risk patients treated with FD do not benefit from an additional 2 yr
      of BCG. In high-risk patients, 3 yr is associated with a reduction in recurrence
      (HR: 1.61; 95% CI, 1.13-2.30; p=0.009) but only when given at FD. There were no
      differences in progression or survival. CONCLUSIONS: There were no differences in
      toxicity between 1/3D and FD. Intermediate-risk patients should be treated with
      FD-1 yr. In high-risk patients, FD-3 yr reduces recurrences as compared with FD-1
      yr but not progressions or deaths. The benefit of the two additional years of
      maintenance should be weighed against its added costs and inconvenience. TRIAL
      REGISTRATION: This study was registered at ClinicalTrials.gov, number
      NCT00002990; http://clinicaltrials.gov/ct2/show/record/NCT00002990.

PMID- 23141051
TI  - Re: Jean J.M.C.H. de la Rosette, Dedan Opondo, Francisco P.J. Daels, et al., on
      behalf of the CROES PCNL Study Group. Categorisation of complications and
      validation of the clavien score for percutaneous nephrolithotomy. Eur Urol
      2012;62:246-55.

PMID- 23141052
TI  - Identification of thymus and activation-regulated chemokine (TARC/CCL17) as a
      potential marker for early indication of disease and prediction of disease
      activity in drug-induced hypersensitivity syndrome (DIHS)/drug rash with
      eosinophilia and systemic symptoms (DRESS).
AB  - BACKGROUND: Drug-induced hypersensitivity syndrome (DIHS)/drug rash with
      eosinophilia and systemic symptoms (DRESS) is a serious acute drug reaction with
      fever, cutaneous eruption, lymphadenopathy, and several visceral dysfunctions.
      Eosinophilia is a common hematological abnormality in DIHS/DRESS suggesting that
      the Th2-type immune response is involved. Thymus and activation-regulated
      chemokine (TARC/CCL17) is a family of CC chemokines known to play an important
      role in Th2-mediated immune-inflammatory processes. OBJECTIVE: We investigated
      the pathogenic role of TARC in patients with DIHS. METHODS: Sera were obtained
      from 8 patients with DIHS, 7 patients with Stevens-Johnson syndrome/Toxic
      epidermal necrolysis (SJS/TEN), and 14 patients with drug-induced maculopapular
      exanthema (MPE). Serum TARC levels were measured by ELISA. TARC levels were then
      compared with clinical symptoms and various hematological parameters. In
      addition, a biopsy was taken from the lesional skin of patients with DIHS and
      stained with anti-TARC Ab and anti-CD11c Ab. RESULTS: Serum TARC levels in
      patients with DIHS were significantly higher than those in patients with SJS/TEN
      and MPE during the acute phase. Serum TARC levels in DIHS patients correlated
      with skin eruptions, serum sIL-2R levels, eosinophil counts, and serum IL-5
      levels. Immunohistochemical staining revealed that TARC was mainly expressed on
      CD11c+ dermal dendritic cells in patients with DIHS. CONCLUSION: Serum TARC
      levels may be associated with the initial presentation of DIHS as well as disease
      activity during the course. Thus, they could be useful as an indicator for early
      diagnosis and assessment of disease activity in DIHS. CD11c+ dendritic cells may
      be the main source of TARC in patients with DIHS.

PMID- 23141053
TI  - The cumulative probability of liveborn multiples after in vitro fertilization: a
      cohort study of more than 10,000 women.
AB  - OBJECTIVE: To estimate the cumulative probability of liveborn multiples after IVF
      to improve patient counseling regarding this significant morbidity. DESIGN:
      Retrospective cohort study. SETTING: Large academic-affiliated infertility
      practice. PATIENT(S): A total of 10,169 women were followed from their first
      fresh, nondonor IVF cycle through up to six fresh and frozen IVF cycles from 2000
      2010. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Delivery of a liveborn
      infant(s). RESULT(S): After three IVF cycles the cumulative live birth rate
      (CLBR) was 53.2%. The singleton, twin, and triplet CLBRs were 38.0%, 14.5%, and
      0.7%. After six IVF cycles the CLBR was 73.8%, with 52.8%, 19.8%, 1.3% for
      singletons, twins, and triplets. Of the 5,433 live births, 71.4% were singletons,
      27.1% were twins, and 1.5% were triplets. Women more than 39 years had the lowest
      incidence of liveborn multiples with CLBRs of 5.2% after three cycles and 9.5%
      after six cycles. The twin CLBR doubled from cycles 1 through 3 with the rate of
      increase slowing from cycles 3 through 6. Although very low in absolute terms,
      the triplet CLBR also doubled from cycles 1 through 3 and doubled again from
      cycles 3 through 6. Of the 1,970 pregnancies that began as multifetal on
      ultrasound, 77.4% resulted in liveborn multiples. CONCLUSION(S): Providers should
      be aware of the cumulative probability of liveborn multiples to effectively
      counsel patients on this important issue. With nearly three-quarters of all women
      having live birth after up to six IVF cycles, it is encouraging to report a low
      incidence of liveborn multiples.

PMID- 23141054
TI  - Novel orexigenic pathway prostaglandin D2-NPY system--involvement in orally
      active orexigenic delta opioid peptide.
AB  - Prostaglandin (PG) D(2), the most abundant PG in the central nervous system
      (CNS), is a bioactive lipid having various central actions including sleep
      induction, hypothermia and modulation of the pain response. We found that
      centrally administered PGD(2) stimulates food intake via the DP(1) among the two
      receptor subtypes for PGD(2) in mice. Hypothalamic mRNA expression of lipocalin
      type PGD synthase (L-PGDS), which catalyzes production of PGD(2) from arachidonic
      acid via PGH(2) in the CNS, was increased after fasting. Central administration
      of antagonist and antisense ODN for the DP(1) receptor remarkably decreased food
      intake, body weight and fat mass. The orexigenic activity of PGD(2) was also
      blocked by an antagonist of Y(1) receptor for NPY, the most potent orexigenic
      peptide in the hypothalamus. Thus, the central PGD(2)-NPY system may play a
      critical role in food intake regulation under normal physiological conditions. We
      also found that orally active orexigenic peptide derived from food protein
      activates the PGD(2)-NPY system, downstream of delta opioid receptor. We revealed
      that the delta agonist peptide, rubiscolin-6-induced orexigenic activity was
      mediated by L-PGDS in the leptomeninges but not parenchyma using conditional
      knockout mice. In this review, we discuss the PGD(2)-NPY system itself, and
      orexigenic signals to activate it.

PMID- 23141055
TI  - Prenylated C6-C3 compounds from the roots of Illicium henryi.
AB  - Eleven prenylated C(6)-C(3) compounds, illihenryifunones A, B (1, 2),
      illihenryifunol A (3), illihenryipyranol A (4), illihenryiones A-G (5-11), and
      three known prenylated C(6)-C(3) compounds (12-14), were isolated from the roots
      of Illicium henryi. Structures of 1-11 were elucidated by spectroscopic methods
      including NMR, HRESIMS, and CD. The absolute configuration of the 11,12-diol
      moiety in 5 was determined by observing its induced circular dichroism after
      addition of Mo(2)(OAc)(4) in DMSO. The absolute configuration of C-11 in 4 was
      determined as S based on the Rh(2)(OCOCF(3))(4)-induced CD data; the absolute
      configuration of 3 was determined as R by comparison of its experimental and
      calculated electronic circular dichroism (ECD). The antioxidant activities of
      compounds 1-14 were also evaluated. Compound 4 exhibited strong antioxidant
      activity with an IC(50) value of 2.97+/-1.30 MUM, whereas compounds 3 and 8
      showed antioxidant activities with IC(50) values of 44.36+/-0.30 and 48.00+/-2.01
      MUM, respectively.

PMID- 23141056
TI  - Triacontyl p-coumarate: an inhibitor of snake venom metalloproteinases.
AB  - Snake venom metalloproteinases (SVMPs) participate in a number of important
      biological, physiological and pathophysiological processes and are primarily
      responsible for the local tissue damage characteristic of viperid snake
      envenomations. The use of medicinal plant extracts as antidotes against animal
      venoms is an old practice, especially against snake envenomations. Such plants
      are sources of many pharmacologically active compounds and have been shown to
      antagonize the effects of some venoms and toxins. The present study explores the
      activity of triacontyl p-coumarate (PCT), an active compound isolated from root
      bark of Bombacopsis glabra vegetal extract (Bg), against harmful effects of
      Bothropoides pauloensis snake venom and isolated toxins (SVMPs or phospholipase
      A(2)). Before inhibition assays, Bg or PCT was incubated with venom or toxins at
      ratios of 1:1 and 1:5 (w/w; venom or isolated toxins/PCT) for 30 min at 37
      degrees C. Treatment conditions were also assayed to simulate snakebite with PCT
      inoculated at either the same venom or toxin site. PCT neutralized
      fibrinogenolytic activity and plasmatic fibrinogen depletion induced by B.
      pauloensis venom or isolated toxin. PCT also efficiently inhibited the
      hemorrhagic (3MDH - minimum hemorrhagic dose injected i.d into mice) and myotoxic
      activities induced by Jararhagin, a metalloproteinase from B. jararaca at 1:5
      ratio (toxin: inhibitor, w/w) when it was previously incubated with PCT and
      injected into mice or when PCT was administered after toxin injection. Docking
      simulations using data on a metalloproteinase (Neuwiedase) structure suggest that
      the binding between the protein and the inhibitor occurs mainly in the active
      site region causing blockade of the enzymatic reaction by displacement of
      catalytic water. Steric hindrance may also play a role in the mechanism since the
      PCT hydrophobic tail was found to interact with the loop associated with
      substrate anchorage. Thus, PCT may provide a alternative to complement ophidian
      envenomation treatments.

PMID- 23141057
TI  - Flip-flopping to the membrane.
AB  - Excitatory synapses that use the neurotransmitter glutamate are highly dynamic,
      constantly changing their character in an activity-dependent manner. In this
      issue of Neuron, Penn et al. (2012) describe a novel mechanism that changes the
      fidelity of glutamate signaling to maintain homeostatic synaptic plasticity.

PMID- 23141058
TI  - Charting a course toward an understanding of schizophrenia.
AB  - Clinical studies suggest a correlation between sleep disturbances and cognitive
      dysfunction in patients with schizophrenia, though the neurobiological basis of
      this association is unclear. In this issue of Neuron, a new study by Phillips et
      al. (2012) describes deficits in the neural oscillations underlying sleep in a
      neurodevelopmental model of the disorder.

PMID- 23141059
TI  - The BOLD plot thickens: sign- and layer-dependent hemodynamic changes with
      activation.
AB  - In this issue of Neuron, Goense et al. (2012) report on high-resolution, layer
      specific measurements of BOLD, cerebral blood volume, and cerebral blood flow in
      regions of positive and negative BOLD associated with a simple visual stimulus.
      The findings strongly suggest that the hemodynamic mechanisms behind negative
      signal changes are quite different from those behind positive signal changes.

PMID- 23141061
TI  - Musical training as a framework for brain plasticity: behavior, function, and
      structure.
AB  - Musical training has emerged as a useful framework for the investigation of
      training-related plasticity in the human brain. Learning to play an instrument is
      a highly complex task that involves the interaction of several modalities and
      higher-order cognitive functions and that results in behavioral, structural, and
      functional changes on time scales ranging from days to years. While early work
      focused on comparison of musical experts and novices, more recently an increasing
      number of controlled training studies provide clear experimental evidence for
      training effects. Here, we review research investigating brain plasticity induced
      by musical training, highlight common patterns and possible underlying mechanisms
      of such plasticity, and integrate these studies with findings and models for
      mechanisms of plasticity in other domains.

PMID- 23141060
TI  - The mysterious motivational functions of mesolimbic dopamine.
AB  - Nucleus accumbens dopamine is known to play a role in motivational processes, and
      dysfunctions of mesolimbic dopamine may contribute to motivational symptoms of
      depression and other disorders, as well as features of substance abuse. Although
      it has become traditional to label dopamine neurons as "reward" neurons, this is
      an overgeneralization, and it is important to distinguish between aspects of
      motivation that are differentially affected by dopaminergic manipulations. For
      example, accumbens dopamine does not mediate primary food motivation or appetite,
      but is involved in appetitive and aversive motivational processes including
      behavioral activation, exertion of effort, approach behavior, sustained task
      engagement, Pavlovian processes, and instrumental learning. In this review, we
      discuss the complex roles of dopamine in behavioral functions related to
      motivation.

PMID- 23141063
TI  - Kinetics of synaptic vesicle refilling with neurotransmitter glutamate.
AB  - After releasing neurotransmitter, synaptic vesicles are retrieved by endocytosis
      and recycled via fast and slow pathways to be reused for synaptic transmission.
      To maintain the synaptic efficacy, vesicles must be refilled with
      neurotransmitter during recycling. However, the refilling speed estimated in
      isolated or reconstructed vesicles is, thus far, too slow to fill up vesicles
      within the period of recycling. Here, we re-examined the vesicle refilling rate
      directly at central glutamatergic synapses in slices, using simultaneous
      presynaptic and postsynaptic whole-cell recording combined with caged glutamate
      photolysis. After washing out vesicular glutamate, refilling of vesicles with
      uncaged glutamate caused a recovery of EPSCs with a time constant of 15 s that
      varied depending upon temperature, age, and cytosolic Cl(-) concentrations. This
      time constant is faster than that of the slow recycling pathway (~30 s) after
      clathrin-mediated endocytosis but is much too slow to fill up vesicles
      replenished through fast recycling pathways (<1 s).

PMID- 23141062
TI  - Activity-mediated AMPA receptor remodeling, driven by alternative splicing in the
      ligand-binding domain.
AB  - The AMPA-type glutamate receptor (AMPAR) subunit composition shapes synaptic
      transmission and varies throughout development and in response to different input
      patterns. Here, we show that chronic activity deprivation gives rise to synaptic
      AMPAR responses with enhanced fidelity. Extrasynaptic AMPARs exhibited changes in
      kinetics and pharmacology associated with splicing of the alternative flip/flop
      exons. AMPAR mRNA indeed exhibited reprogramming of the flip/flop exons for GluA1
      and GluA2 subunits in response to activity, selectively in the CA1 subfield.
      However, the functional changes did not directly correlate with the mRNA
      expression profiles but result from altered assembly of GluA1/GluA2 subunit
      splice variants, uncovering an additional regulatory role for flip/flop splicing
      in excitatory signaling. Our results suggest that activity-dependent AMPAR
      remodeling underlies changes in short-term synaptic plasticity and provides a
      mechanism for neuronal homeostasis.

PMID- 23141064
TI  - Visual stimulation reverses the directional preference of direction-selective
      retinal ganglion cells.
AB  - Direction selectivity in the retina is mediated by direction-selective ganglion
      cells. These cells are part of a circuit in which they are asymmetrically wired
      to inhibitory neurons. Thus, they respond strongly to an image moving in the
      preferred direction and weakly to an image moving in the opposite (null)
      direction. Here, we demonstrate that adaptation with short visual stimulation of
      a direction-selective ganglion cell using drifting gratings can reverse this
      cell's directional preference by 180 degrees . This reversal is robust, long
      lasting, and independent of the animal's age. Our findings indicate that, even
      within circuits that are hardwired, the computation of direction can be altered
      by dynamic circuit mechanisms that are guided by visual stimulation.

PMID- 23141065
TI  - Decoupling of sleep-dependent cortical and hippocampal interactions in a
      neurodevelopmental model of schizophrenia.
AB  - Rhythmic neural network activity patterns are defining features of sleep, but
      interdependencies between limbic and cortical oscillations at different
      frequencies and their functional roles have not been fully resolved. This is
      particularly important given evidence linking abnormal sleep architecture and
      memory consolidation in psychiatric diseases. Using EEG, local field potential
      (LFP), and unit recordings in rats, we show that anteroposterior propagation of
      neocortical slow-waves coordinates timing of hippocampal ripples and prefrontal
      cortical spindles during NREM sleep. This coordination is selectively disrupted
      in a rat neurodevelopmental model of schizophrenia: fragmented NREM sleep and
      impaired slow-wave propagation in the model culminate in deficient ripple-spindle
      coordination and disrupted spike timing, potentially as a consequence of
      interneuronal abnormalities reflected by reduced parvalbumin expression. These
      data further define the interrelationships among slow-wave, spindle, and ripple
      events, indicating that sleep disturbances may be associated with state-dependent
      decoupling of hippocampal and cortical circuits in psychiatric diseases.

PMID- 23141067
TI  - Presynaptically released Cbln1 induces dynamic axonal structural changes by
      interacting with GluD2 during cerebellar synapse formation.
AB  - Differentiation of pre- and postsynaptic sites is coordinated by reciprocal
      interaction across synaptic clefts. At parallel fiber (PF)-Purkinje cell (PC)
      synapses, dendritic spines are autonomously formed without PF influence. However,
      little is known about how presynaptic structural changes are induced and how they
      lead to differentiation of mature synapses. Here, we show that Cbln1 released
      from PFs induces dynamic structural changes in PFs by a mechanism that depends on
      postsynaptic glutamate receptor delta2 (GluD2) and presynaptic neurexin (Nrx).
      Time-lapse imaging in organotypic culture and ultrastructural analyses in vivo
      revealed that Nrx-Cbln1-GluD2 signaling induces PF protrusions that often formed
      circular structures and encapsulated PC spines. Such structural changes in PFs
      were associated with the accumulation of synaptic vesicles and GluD2, leading to
      formation of mature synapses. Thus, PF protrusions triggered by Nrx-Cbln1-GluD2
      signaling may promote bidirectional maturation of PF-PC synapses by a positive
      feedback mechanism.

PMID- 23141066
TI  - Regulation of DLK-1 kinase activity by calcium-mediated dissociation from an
      inhibitory isoform.
AB  - MAPKKK dual leucine zipper-bearing kinases (DLKs) are regulators of synaptic
      development and axon regeneration. The mechanisms underlying their activation are
      not fully understood. Here, we show that C. elegans DLK-1 is activated by a
      Ca(2+)-dependent switch from inactive heteromeric to active homomeric protein
      complexes. We identify a DLK-1 isoform, DLK-1S, that shares identical kinase and
      leucine zipper domains with the previously described long isoform DLK-1L but acts
      to inhibit DLK-1 function by binding to DLK-1L. The switch between homo- or
      heteromeric DLK-1 complexes is influenced by Ca(2+) concentration. A conserved
      hexapeptide in the DLK-1L C terminus is essential for DLK-1 activity and is
      required for Ca(2+) regulation. The mammalian DLK-1 homolog MAP3K13 contains an
      identical C-terminal hexapeptide and can functionally complement dlk-1 mutants,
      suggesting that the DLK activation mechanism is conserved. The DLK activation
      mechanism is ideally suited for rapid and spatially controlled signal
      transduction in response to axonal injury and synaptic activity.

PMID- 23141068
TI  - Zinc potentiates GluK3 glutamate receptor function by stabilizing the ligand
      binding domain dimer interface.
AB  - Kainate receptors (KARs) play a key role in the regulation of synaptic networks.
      Here, we show that zinc, a cation released at a subset of glutamatergic synapses,
      potentiates glutamate currents mediated by homomeric and heteromeric KARs
      containing GluK3 at 10-100 MUM concentrations, whereas it inhibits other KAR
      subtypes. Potentiation of GluK3 currents is mainly due to reduced
      desensitization, as shown by kinetic analysis and desensitization mutants.
      Crystallographic and mutation analyses revealed that a specific zinc binding site
      is formed at the base of the ligand binding domain (LBD) dimer interface by a
      GluK3-specific aspartate (Asp759), together with two conserved residues, His762
      and Asp730, the latter located on the partner subunit. In addition, we propose
      that tetrameric GluK2/GluK3 receptors are likely assembled as pairs of
      heterodimeric LBDs. Therefore, zinc binding stabilizes the labile GluK3 dimer
      interface, slows desensitization, and potentiates currents, providing a mechanism
      for KAR potentiation at glutamatergic synapses.

PMID- 23141069
TI  - A preferentially segregated recycling vesicle pool of limited size supports
      neurotransmission in native central synapses.
AB  - At small central synapses, efficient turnover of vesicles is crucial for stimulus
      driven transmission, but how the structure of this recycling pool relates to its
      functional role remains unclear. Here we characterize the organizational
      principles of functional vesicles at native hippocampal synapses with nanoscale
      resolution using fluorescent dye labeling and electron microscopy. We show that
      the recycling pool broadly scales with the magnitude of the total vesicle pool,
      but its average size is small (~45 vesicles), highly variable, and regulated by
      CDK5/calcineurin activity. Spatial analysis demonstrates that recycling vesicles
      are preferentially arranged near the active zone and this segregation is
      abolished by actin stabilization, slowing the rate of activity-driven exocytosis.
      Our approach reveals a similarly biased recycling pool distribution at synapses
      in visual cortex activated by sensory stimulation in vivo. We suggest that in
      small native central synapses, efficient release of a limited pool of vesicles
      relies on their favored spatial positioning within the terminal.

PMID- 23141070
TI  - Correlated variability in laminar cortical circuits.
AB  - Despite the fact that strong trial-to-trial correlated variability in responses
      has been reported in many cortical areas, recent evidence suggests that neuronal
      correlations are much lower than previously thought. Here, we used multicontact
      laminar probes to revisit the issue of correlated variability in primary visual
      (V1) cortical circuits. We found that correlations between neurons depend
      strongly on local network context--whereas neurons in the input (granular) layers
      showed virtually no correlated variability, neurons in the output layers
      (supragranular and infragranular) exhibited strong correlations. The laminar
      dependence of noise correlations is consistent with recurrent models in which
      neurons in the granular layer receive intracortical inputs from nearby cells,
      whereas supragranular and infragranular layer neurons receive inputs over larger
      distances. Contrary to expectation that the output cortical layers encode
      stimulus information most accurately, we found that the input network offers
      superior discrimination performance compared to the output networks.

PMID- 23141071
TI  - Sensitivity to complex statistical regularities in rat auditory cortex.
AB  - Neurons in auditory cortex are sensitive to the probability of stimuli: responses
      to rare stimuli tend to be stronger than responses to common ones. Here, intra-
      and extracellular recordings from the auditory cortex of halothane-anesthetized
      rats revealed the existence of a finer sensitivity to the structure of sound
      sequences. Using oddball sequences in which the order of stimulus presentations
      is periodic, we found that tones in periodic sequences evoked smaller responses
      than the same tones in random sequences. Significant reduction in the responses
      to the common tones in periodic relative to random sequences occurred even when
      these tones consisted of 95% of the stimuli in the sequence. The reduction in
      responses paralleled the complexity of the sound sequences and could not be
      explained by short-term effects of clusters of deviants on succeeding standards.
      We conclude that neurons in auditory cortex are sensitive to the detailed
      structure of sound sequences over timescales of minutes.

PMID- 23141072
TI  - Neural mechanisms of speed-accuracy tradeoff.
AB  - Intelligent agents balance speed of responding with accuracy of deciding.
      Stochastic accumulator models commonly explain this speed-accuracy tradeoff by
      strategic adjustment of response threshold. Several laboratories identify
      specific neurons in prefrontal and parietal cortex with this accumulation
      process, yet no neurophysiological correlates of speed-accuracy tradeoff have
      been described. We trained macaque monkeys to trade speed for accuracy on cue
      during visual search and recorded the activity of neurons in the frontal eye
      field. Unpredicted by any model, we discovered that speed-accuracy tradeoff is
      accomplished through several distinct adjustments. Visually responsive neurons
      modulated baseline firing rate, sensory gain, and the duration of perceptual
      processing. Movement neurons triggered responses with activity modulated in a
      direction opposite of model predictions. Thus, current stochastic accumulator
      models provide an incomplete description of the neural processes accomplishing
      speed-accuracy tradeoffs. The diversity of neural mechanisms was reconciled with
      the accumulator framework through an integrated accumulator model constrained by
      requirements of the motor system.

PMID- 23141074
TI  - Reading with sounds: sensory substitution selectively activates the visual word
      form area in the blind.
AB  - Using a visual-to-auditory sensory-substitution algorithm, congenitally fully
      blind adults were taught to read and recognize complex images using "soundscapes"
      -sounds topographically representing images. fMRI was used to examine key
      questions regarding the visual word form area (VWFA): its selectivity for letters
      over other visual categories without visual experience, its feature tolerance for
      reading in a novel sensory modality, and its plasticity for scripts learned in
      adulthood. The blind activated the VWFA specifically and selectively during the
      processing of letter soundscapes relative to both textures and visually complex
      object categories and relative to mental imagery and semantic-content controls.
      Further, VWFA recruitment for reading soundscapes emerged after 2 hr of training
      in a blind adult on a novel script. Therefore, the VWFA shows category
      selectivity regardless of input sensory modality, visual experience, and long
      term familiarity or expertise with the script. The VWFA may perform a flexible
      task-specific rather than sensory-specific computation, possibly linking letter
      shapes to phonology.

PMID- 23141073
TI  - High-resolution fMRI reveals laminar differences in neurovascular coupling
      between positive and negative BOLD responses.
AB  - The six cortical layers have distinct anatomical and physiological properties,
      like different energy use and different feedforward and feedback connectivity. It
      is not known if and how layer-specific neural processes are reflected in the fMRI
      signal. To address this question we used high-resolution fMRI to measure BOLD,
      CBV, and CBF responses to stimuli that elicit positive and negative BOLD signals
      in macaque primary visual cortex. We found that regions with positive BOLD
      responses had parallel increases in CBV and CBF, whereas areas with negative BOLD
      responses showed a decrease in CBF but an increase in CBV. For positive BOLD
      responses, CBF and CBV increased in the center of the cortex, but for negative
      BOLD responses, CBF decreased superficially while CBV increased in the center.
      Our findings suggest different mechanisms for neurovascular coupling for BOLD
      increases and decreases, as well as laminar differences in neurovascular
      coupling.

PMID- 23141076
TI  - Quantifying accurate calorie estimation using the "think aloud" method.
AB  - OBJECTIVE: Clients often have limited time in a nutrition education setting. An
      improved understanding of the strategies used to accurately estimate calories may
      help to identify areas of focused instruction to improve nutrition knowledge.
      METHODS: A "Think Aloud" exercise was recorded during the estimation of calories
      in a standard dinner meal (415 kcal) in 15 nutrition-trained and 15 untrained
      subjects. Accuracy of participant estimation was assessed, and estimation
      strategies were compared in accurate vs inaccurate estimators. RESULTS: Accurate
      participants were more likely to demonstrate an ability to convert between common
      portion size measurements and serving sizes, possess some knowledge of energy
      density, and properly implement basic math skills. CONCLUSIONS AND IMPLICATIONS:
      The "Think Aloud" methodology was informative in assessing the cognitive
      processes behind a nutrition exercise, and further use is warranted. Focused
      instruction in portion size conversion, energy density, and the use of math
      skills may enhance calorie estimation accuracy.

PMID- 23141075
TI  - The emergence and representation of knowledge about social and nonsocial
      hierarchies.
AB  - Primates are remarkably adept at ranking each other within social hierarchies, a
      capacity that is critical to successful group living. Surprisingly little,
      however, is understood about the neurobiology underlying this quintessential
      aspect of primate cognition. In our experiment, participants first acquired
      knowledge about a social and a nonsocial hierarchy and then used this information
      to guide investment decisions. We found that neural activity in the amygdala
      tracked the development of knowledge about a social, but not a nonsocial,
      hierarchy. Further, structural variations in amygdala gray matter volume
      accounted for interindividual differences in social transitivity performance.
      Finally, the amygdala expressed a neural signal selectively coding for social
      rank, whose robustness predicted the influence of rank on participants'
      investment decisions. In contrast, we observed that the linear structure of both
      social and nonsocial hierarchies was represented at a neural level in the
      hippocampus. Our study implicates the amygdala in the emergence and
      representation of knowledge about social hierarchies and distinguishes the domain
      general contribution of the hippocampus.

PMID- 23141077
TI  - Prevalence of corneal astigmatism before cataract surgery in Chinese patients.
AB  - PURPOSE: To assess the demographics and distribution of corneal astigmatism
      before cataract surgery in Chinese patients. SETTING: State Key Laboratory of
      Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou,
      China. DESIGN: Clinic-based cross-sectional study. METHODS: From July 2009 to May
      2011, preoperative bilateral partial coherence interferometry (IOLMaster) was
      performed in consecutive patients having cataract surgery. Patient demographics
      and keratometric data were recorded. RESULTS: The mean age of the 2849 patients
      (4831 eyes) was 70.56 years +/- 9.55 (SD); there was a predominance of women
      patients (64.0%). The mean axial length was 23.58 +/- 1.13 mm. The mean corneal
      astigmatism in this cohort was 1.01 D (range 0.05 to 6.59 D). Corneal astigmatism
      was between 0.25 D and 1.25 D in 67.7% of eyes, 1.25 D or higher in 27.5% eyes,
      and less than 0.25 D in 4.8% of eyes. Astigmatism was with the rule in 25.1% of
      eyes, against the rule (ATR) in 58.2% of eyes, and oblique in 16.7% of eyes. The
      mean steep keratometry measurement was 44.76 +/- 1.56 D. Against-the-rule
      astigmatism increased significantly with older age. CONCLUSIONS: Corneal
      astigmatism largely fell between 0.25 D and 1.25 D in these predominantly elderly
      female Chinese patients, and ATR astigmatism increased with age. FINANCIAL
      DISCLOSURE: No author has a financial or proprietary interest in any material or
      method mentioned.

PMID- 23141078
TI  - Quality of corneal lamellar cuts quantified using atomic force microscopy.
AB  - PURPOSE: To quantify the cut quality of lamellar dissections made with the
      femtosecond laser using atomic force microscopy (AFM). SETTING: Bascom Palmer Eye
      Institute, University of Miami Miller School of Medicine, Miami, Florida, USA.
      DESIGN: Experimental study. METHODS: Experiments were performed on 3 pairs of
      human cadaver eyes. The cornea was thinned to physiologic levels by placing the
      globe, cornea side down, in 25% dextran for 24 hours. The eyes were reinflated to
      normal pressures by injecting a balanced salt solution into the vitreous cavity.
      The eyes were placed in a holder, the epithelium was removed, and the eyes were
      cut with a Visumax femtosecond laser. The energy level was 180 nJ for the right
      eye and 340 nJ for the left eye of each pair. The cut depths were 200 MUm, 300
      MUm, and 400 MUm, with the cut depth maintained for both eyes of each pair. A
      12.0 mm trephination was then performed. The anterior portion of the lamellar
      surface was placed in a balanced salt solution and imaged with AFM. As a control,
      the posterior surface was placed in 2% formalin and imaged with environmental
      scanning electron microscopy (SEM). Four quantitative parameters (root-mean
      square deviation, average deviation, skewness, kurtosis) were calculated from the
      AFM images. RESULTS: From AFM, the 300 MUm low-energy cuts were the smoothest.
      Similar results were seen qualitatively in the environmental SEM images.
      CONCLUSION: Atomic force microscopy provided quantitative information on the
      quality of lamellar dissections made using a femtosecond laser, which is useful
      in optimizing patient outcomes in refractive and lamellar keratoplasty surgeries.

PMID- 23141079
TI  - Menopause, hormone treatment and urinary incontinence at midlife.
AB  - Whether there is any association between urinary incontinence and menopause is
      the subject of debate, partly due to the fact it is difficult to tell the
      difference between the effects of menopause and those of ageing. For some time it
      was hoped that hormonal treatment for menopause would be beneficial for urinary
      incontinence because there are hormonal receptors in the urinary tract. The goal
      of this survey of current knowledge on the subject is to explore thoroughly the
      relationship between menopause and urinary incontinence. Our study is based on a
      review of the literature dealing with the epidemiology of urinary incontinence in
      women aged between 45 and 60, and the effects of hormonal treatment with respect
      to the symptoms of involuntary loss of urine. Analysis of the epidemiological
      data drawn from large cohorts shows that on the one hand, the menopause has
      little if any impact on the risk of urinary incontinence, and on the other hand
      that the effects of oestrogen medication on urinary incontinence vary according
      to how it is administered and the type of incontinence. The effect of oral
      hormone treatments for menopause is rather negative with respect to stress
      incontinence. Vaginal treatment appears to be beneficial for overactive bladder
      symptoms.

PMID- 23141080
TI  - Older black adult osteoarthritis pain communication.
AB  - A quantitative descriptive secondary data analysis design was used to describe
      older black adult communication of osteoarthritis pain and the communication
      strategies used to convey the pain information. Pain content from 74 older black
      adults with persistent osteoarthritis pain was analyzed using criteria from the
      American Pain Society arthritis pain management guidelines that included type of
      pain (nociceptive/neuropathic), quality of pain, source, location, intensity,
      duration/time course, pain affect, effect on personal lifestyle, functional
      status, current pain treatments, use of recommended glucosamine sulfate,
      effectiveness of prescribed treatments, prescription analgesic side effects,
      weight management to ideal body weight, exercise regimen or physical therapy
      and/or occupational therapy, and indications for surgery. Communication
      strategies were analyzed with criteria derived from Communication Accommodation
      Theory that included being clear, using medical syntax, using ethnic specific
      syntax, being explicit, and staying on topic when discussing pain. The majority
      of communicated pain content included pain location, intensity, and timing.
      Regarding communication strategies, most of the older black adults used specific
      descriptions of pain and remained on topic. Fewer used explicit descriptions of
      pain that produced a vivid mental image, and few used medical terminology. Use of
      medical syntax and more explicit descriptions might improve communication about
      pain between health care practitioners and patients. Practitioners might assist
      older black adults with persistent osteoarthritis pain to communicate important
      clinical pain information by helping them to use relevant medical terminology and
      more explicit pain descriptions when discussing pain management. 

PMID- 23141081
TI  - [Stem cell therapy for the treatment of coronary heart disease: safety
      evaluation].

PMID- 23141082
TI  - [Beneficial effects of liver X receptor agonist on adipose-derived mesenchymal
      stem cells transplantation in mice with myocardial infarction].
AB  - OBJECTIVE: To investigate the effects of liver X receptor (LXR) agonist on
      adipose-derived mesenchymal stem cells (AD-MSCs) implantation into infarcted
      hearts of mice. METHOD: AD-MSC(Fluc+) which stably expressed firefly luciferase
      (Fluc) were isolated from beta-actin-Fluc transgenic mice and characterized by
      flow cytometry. Male FVB mice were randomly allocated into the following four
      groups (n = 10 each): (1) sham group; (2) MI + PBS group; (3) MI + AD-MSC(Fluc+)
      group; (4) MI + AD-MSC(Fluc+) + LXR agonist (T0901317) group. AD-MSC(Fluc+) or
      PBS were injected intramyocardial into peri-infarcted region of mice heart after
      permanent left anterior descending (LAD) artery ligation. Bioluminescence imaging
      (BLI) was performed for quantification of injected cells retention and survival.
      Cardiac function was evaluated by echocardiography. RESULTS: The AD-MSC(Fluc+)
      were positive for CD44 and CD90 by flow cytometry. BLI evidenced the firefly
      luciferase expression of AD-MSC(Fluc+) which was positively correlated with cell
      numbers (r(2) = 0.98). The results of BLI in vivo revealed that LXR agonist could
      improve the survival of AD-MSC(Fluc+) at day 7, 14 and 21 after transplantation
      compared with AD-MSC(Fluc+) alone group. Cardiac function was further improved in
      combination therapy group compared with AD-MSC(Fluc+) alone group (P < 0.05).
      CONCLUSIONS: LXR agonist T0901317 can improve the retention and survival of
      intramyocardial injected AD-MSC(Fluc+) post-MI, and the combination therapy of
      T0901317 and AD-MSC(Fluc+) has a synergetic effect on improving cardiac function
      in this model.

PMID- 23141083
TI  - [The changes of cardioelectrical activity of rat with myocardial infarction
      receiving sarcoplasmic reticulum Ca(2+)-ATPase gene modified bone marrow stem
      cell transplantation by microelectrode array technology].
AB  - OBJECTIVE: Therapy effects and cardiac electrical activity comparison of bone
      marrow stem cells (BMSCs) transplantation and sarcoplasmic reticulum Ca(2+)
      ATPase (SERCA2a) gene modified BMSCs transplantation after acute myocardial
      infarction (AMI) in rats. METHODS: Rats with AMI were divided into 4 groups (n =
      30) randomly: normal group (n = 6), saline group (control group, n = 8), BMSCs
      transplantation group (BMSCs group, n = 8) and SERCA2a gene modified BMSCs
      transplantation group (BMSCs + rAd.SERCA2a group, n = 8). After 14 days, cardiac
      function was evaluated by echocardiography and heart electrical activity was
      evaluated by electrocardiogram and microelectrode array (MEA) technology.
      RESULTS: (1) The transduction ratio of rAd.SERCA2a to BMSCs were 80% to 90%. (2)
      Left ventricular ejection fraction on 14 days after therapy was significantly
      higher in BMSCs group and BMSCs + rAd.SERCA2a group than in control group (all P
      < 0.05). (3) QT duration was significantly shorter [(80.30 +/- 6.53) ms vs.
      (105.31 +/- 21.89) ms, P < 0.05] and ventricular premature beats less frequent in
      BMSCs + rAd. SERCA2a group than in the control group. (4) MEA results suggested
      that isolated heart beat was significantly slowed down and frequent ventricular
      arrhythmias and atrioventricular block were recorded in control group. The
      maximum field potential and field potential duration on infarcted myocardium area
      in BMSCs group and BMSCs + rAd.SERCA2a group were significantly longer than those
      in control group[the maximum field potential: (0.51 +/- 0.15), (0.55 +/- 0.16),
      (0.23 +/- 0.10) mV; field potential duration: (104.5 +/- 25.43), (107.67 +/-
      24.01), (63.00 +/- 20.34) ms; all P < 0.05]. (5) The conduction time was the
      shortest and the cardiac electrical conduction consistency in myocardial
      infarction tissue was significantly improved in BMSCs + rAd.SERCA2a group.
      CONCLUSIONS: BMSCs and SERCA2a gene modified BMSCs transplantation could
      significantly improve cardiac function and BMSCs + rAd.SERCA2a could also
      effectively improve electrical conduction of infarcted myocardium and attenuate
      the incidence of arrhythmia after myocardial infarction in rats.

PMID- 23141084
TI  - [Effect of gene modified mesenchymal stem cells overexpression human receptor
      activity modified protein 1 on inflammation and cardiac repair in a rabbit model
      of myocardial infarction].
AB  - OBJECTIVE: To investigate the effect of mesenchymal stem cells (MSCs)
      overexpressing human receptor activity modified protein 1 (hRAMP1) by adenovirus
      vector on infarction related inflammation and cardiac repair in a rabbit model of
      myocardial infarction (MI). METHODS: Thirty rabbits underwent coronary artery
      ligation for 60 minutes followed by 24 hours reperfusion and divided into
      MSC(hRAMP1) group (intravenously injection of MSCs transfected with adenovirus
      vector encoding hRAMP1 gene enhanced green fluorescent protein, EGFP, n = 10),
      MSC(null) group (MSCs transfected with adenovirus vector encoding only EGFP
      without hRAMP1 gene, n = 10) and control group (equally volume of phosphate
      buffered saline, PBS, n = 10). The plasma level of tumor necrosis factor-alpha
      (TNF-alpha) and interleukin-10 (IL-10) were quantified by ELISA assay at before
      and 1, 3, 7, 28 days after induction of MI. The expression of nuclear factor
      kappaB (NF-kappaB) and hRAMP1 in infracted myocardium were measured by Western
      blot at 1, 3, 7, 28 day following MI. The area of MI and collagen deposition and
      fibrosis were evaluated by TTC staining and Masson staining, respectively.
      RESULTS: Area of MI and collagen content were significantly reduced in
      MSC(hRAMP1) group compared those in MSC(null) and control group [(10.1 +/- 2.9)%
      vs. (30.6 +/- 2.7)% and (22.5 +/- 3.2)%, P < 0.05]. Myocardial expression of NF
      kappaB and plasma TNF-alpha[7 days after transplantation: (97.2 +/- 6.7) pg/ml
      vs. (207.6 +/- 12.7) pg/ml and (153.2 +/- 9.9) pg/ml, P < 0.05] were also lower
      while plasma level of IL-10 [7 days after transplantation: (238.5 +/- 17.5) pg/ml
      vs. (177.3 +/- 19.8) pg/ml and (244.6 +/- 27.3) pg/ml, P < 0.05] was
      significantly higher in MSC(hRAMP1) group than in MSC(null) and control group.
      CONCLUSION: MSCs overexpression hRAMP1 could further reduce area of MI possibly
      through inhibiting the myocardial expression of NF-kappaB and reducing the plasma
      TNF-alpha level and raising plasma IL-10 level.

PMID- 23141085
TI  - [Association between fractional flow reserve and quantitative coronary
      angiography parameters in intermediate coronary artery stenosis].
AB  - OBJECTIVE: To explore the relationship between quantitative coronary angiography
      (QCA) parameters and fractional flow reserve (FFR) for identifying ideal
      angiographic parameters predictive of myocardial ischemia. METHODS: The study
      included 121 lesions with QCA and FFR data from 106 patients [mean age: (63 +/-
      10) years]. The lesions were grouped into FFR > 0.75 group and FFR <= 0.75 group.
      Assessed parameters by QCA included percentage diameter stenosis, minimum luminal
      diameter (MLD), percentage area stenosis, minimum luminal area (MLA), reference
      vessel diameter (RVD) and lesion length (LL). Correlation analysis was used to
      identify the relationship between QCA parameters and FFR value, and receiver
      operating characteristic (ROC) curve was used to determine parameters predictive
      of FFR <= 0.75. RESULTS: LL was significantly higher [(14.8 +/- 7.9) mm vs. (10.7
      +/- 5.4) mm, P = 0.024] while MLD [(1.47 +/- 0.31) mm vs. (1.82 +/- 0.51) mm, P =
      0.028], RVD [(2.30 +/- 0.50) mm vs. (2.81 +/- 0.64) mm, P = 0.036], and MLA
      [(2.30 +/- 1.50) mm(2) vs. (3.60 +/- 2.30) mm(2), P = 0.038] were significantly
      lower in FFR <= 0.75 group than in FFR > 0.75 group. LL (r = -0.209, P = 0.040)
      was negatively correlated with FFR, and MLD (r = 0.414, P = 0.040), RVD (r =
      0.303, P = 0.000) and MLA (r = 0.315, P = 0.002) were positively correlated with
      FFR. ROC analysis showed that MLD >= 1.6 mm was the best cut-off value to predict
      FFR > 0.75 with sensitivity 63%, specificity 82%, and positive predictive value
      96%. CONCLUSIONS: QCA derived anatomic parameters of intermediate coronary
      lesions correlate to FFR value in some extent. MLD >= 1.6 mm is the best cut-off
      value to predict FFR > 0.75 in patients with intermediate coronary lesions.

PMID- 23141086
TI  - [Evaluation of very early neointimal coverage post drug-eluting stent
      implantation using optical coherence tomography].
AB  - OBJECTIVE: To investigate the neointimal coverage at the very early phase after
      drug-eluting stent (DES) implantation using optical coherence tomography (OCT).
      METHODS: OCT examination was performed immediately after stent deployment and
      about one week post stenting in 12 patients with coronary artery disease to
      detect neointimal coverage and stent thrombus. Sirolimus eluting stent
      implantation was also performed in 5 healthy Chinese minipigs, OCT and
      histopathology examination were made one week later in these minipigs. RESULTS:
      (1) Twenty-nine DES were implanted in 12 patients. There was no major
      cardiovascular event post stenting. The mean time of follow-up was (7.7 +/- 2.6)
      d, the mean percentage of stent coverage was (21.8 +/- 17.7)%, and neointimal
      hyperplasia thickness was (42.9 +/- 32.2) um and the percentage of malapposition
      struts was (1.5 +/- 3.0)%, respectively. Mural stent thrombus was found in 2 of
      the 12 patients (the percentage is 16.7%). (2) In the minipigs model, OCT
      evidenced that (43.2 +/- 11.5)% struts were covered by neointima with a mean
      neointimal hyperplasia thickness of (24.0 +/- 8.5) um at one week. Histopathology
      examination illustrated that the neointima was mainly consisted of proteoglycan,
      inflammation cells, fibrin and organized thrombus at the very early phase after
      DES implantation, while endothelial cells were barely found on the neointima.
      CONCLUSIONS: Neointimal coverage is found as early as one week after DES
      implantation by OCT. The covered struts rate is very low and the main components
      of neointima are proteoglycan, inflammation cells, fibrin and organized thrombus.
      Re-endothelialization is rather poor at the very early phase post DES
      implantation.

PMID- 23141087
TI  - [Association between plasma adiponectin and small, dense low density lipoprotein
      in patients with coronary artery disease].
AB  - OBJECTIVE: To observe the association between adiponectin and small dense low
      density lipoprotein (sLDL-c) in coronary artery disease (CAD) patients.
      Furthermore, we sought to determine the association between single nucleotide
      polymorphisms (SNP) rs1501299 (+276G/T), rs266729 (-11365C/G) and the incidence
      of CAD. METHODS: Consecutive subjects with chest discomfort were examined by
      coronary angiography and divided into non-CAD [n = 250, 147 male, mean age (60.26
      +/- 7.52) years] and CAD [n = 267, 153 male, mean age (60.79 +/- 9.63) years]
      groups. Blood samples were collected from all participants following an overnight
      fasting for at least 12 hours. Plasma adiponectin levels were measured by
      competitive enzyme-linked immunosorbent assay (ELISA). The serum levels of sLDL-C
      and oxidized low-density lipoprotein (ox-LDL) were determined by ELISA. Genotypes
      in rs1501299 and rs266729 of the adiponectin were determined by polymerase chain
      reaction (PCR). RESULTS: 1. The adiponectin levels were significantly lower
      [(306.17 +/- 74.52) mg/L vs. (321.78 +/- 86.28) mg/L], whereas sLDL-C and ox-LDL
      levels were significantly higher [(276.30 +/- 45.55) ng/L vs. (249.00 +/- 32.02)
      ng/L and (545.06 +/- 115.46) ug/L vs. (497.74 +/- 106.09) ug/L, P < 0.05] in CAD
      group than non-CAD group. 2. Adiponectin level was negatively associated with
      sLDL-C, whereas sLDL-C positively correlated with ox-LDL in all subjects. 3.
      Genotype distribution and allele frequencies of rs1501299 and rs266729 were
      similar between CAD and non-CAD subjects and not related to the serum levels of
      adiponectin, sLDL-C and ox-LDL. CONCLUSIONS: Reduced adiponectin and increased
      sLDL-C were independent risk factors for coronary artery disease. Genetic
      polymorphisms in rs1501299 and rs266729 were not linked with coronary artery
      disease.

PMID- 23141088
TI  - [Causes of non-response to cardiac resynchronization therapy in heart failure
      patients with permanent atrial fibrillation].
AB  - OBJECTIVE: To evaluate the long-term effects and analyze causes of non-response
      to cardiac resynchronization therapy (CRT) in heart failure (HF) patients with
      permanent atrial fibrillation (AF). METHODS: Thirty-three patients with HF and AF
      [29 men, mean age (61 +/- 10) years, NYHA class III or IV, left ventricular
      ejection fraction (LVEF) <= 35%, QRS >= 120 ms in 31 cases] underwent bi
      ventricular pacing (n = 26) or bi-ventricular pacing and atrioventricular node
      ablation (AVN-ablation, n = 7) were included in this study. Non-response was
      defined: the increase of left ventricular ejection fraction (LVEF) was less than
      15%. Patients were followed-up for 4 years. RESULTS: Six patients died during
      follow up. Non-responder to CRT was observed in 6 out of 27 survived patients
      (22.22%). Six out of 7 patients underwent AVN-ablation were in responder group
      and 1 in non-responder group. Comparing with responder group, the baseline LVEF
      was significantly higher (37% vs. 32%, P = 0.003), and the history of HF was
      significantly longer (6.3 years vs. 4.1 years, P = 0.039), pulmonary artery
      pressure was significantly higher (53 vs. 32 mm Hg, P = 0.027), bi-ventricular
      pacing percentage (BIVP%) was significantly lower (75.86% vs. 91.73%, P = 0.007)
      in non-responder group. CONCLUSIONS: Higher LVEF, longer HF history, higher
      pulmonary artery pressure and lower BIVP% are factors linked with non-responses
      to CRT in this patient cohort. CRT plus AVN-ablation is associated with high
      response rate to CRT in this patient cohort.

PMID- 23141089
TI  - [Comparison on clinical features between dilated cardiomyopathy patients with or
      without pulmonary hypertension].
AB  - OBJECTIVE: The clinical data of dilated cardiomyopathy (DCM) patients with or
      without pulmonary hypertension (PH) diagnosed by echocardiography were compared.
      METHODS: During January 2007 to December 2009, 61 cases of DCM with PH and 51
      cases of DCM without PH were admitted in our department. The demographic and
      clinical data, heart function, echocardiography and serum total bilirubin and
      creatinine levels of all patients were analyzed. RESULTS: Sex, age, vital signs,
      combined diseases and arrhythmias as well as the serum creatinine level [(103.5
      +/- 49.7) umol/L vs. (90.3 +/- 37.3) umol/L, P > 0.05] were similar between the
      two groups, while the incidence of NYHA III and IV (95% vs. 65%), the left
      ventricle end-systolic dimension[(71.0 +/- 9.6) mm vs. (65.5 +/- 7.2) mm],
      dimension of the left atrium [(52.8 +/- 8.93) mm vs. (43.9 +/- 6.3) mm], right
      ventricular outflow tract [(29.1 +/- 5.3) mm vs. (22.1 +/- 3.3) mm] incidence of
      pericardial effusion (29/61 vs. 7/51) and the serum total bilirubin level [(45.3
      +/- 31.8) umol/L vs. (19.5 +/- 9.08) umol/L] were significantly higher while
      ejective fraction was significantly lower in DCM with PH than those in DCM
      without PH (0.28 +/- 0.10 vs. 0.36 +/- 0.10, all P < 0.05). CONCLUSION: DCM
      patients with PH is linked with worse clinical features than DCM patients without
      PH.

PMID- 23141090
TI  - [Clinical experience of supplying sodium chloride for the treatment of patients
      with severe heart failure].
AB  - OBJECTIVE: To observe the effect and safety of supplying sodium chloride in the
      treatment of patients with severe heart failure. METHODS: Consecutive 51
      hospitalized patients with severe heart failure and cardiac edema were included
      in this study. Normal diet (6 g NaCl/d) was supplied to all patients. On the
      basis of controlling fluid intake and treating related etiological factors as
      well as standard medications including furosemide for severe heart failure,
      patients with mild hyponatremia (serum sodium level 130 - 134 mmol/L) ate
      additional salted vegetables, patients with moderate hyponatremia (serum sodium
      level 125 - 129 mmol/L) and severe hyponatremia (serum sodium level < 125 mmol/L)
      ate additional salted vegetables and were received additionally intravenous
      3%NaCl hypertonic saline infusion (10 ml/h) until reaching normal serum sodium
      level. RESULTS: On admission, 37.25% (19/51) patients had hyponatremia. During
      the first two weeks hospitalization period, 88.24% (45/51) patients were treated
      with intravenous diuretics and total incidence of hyponatremia was 64.71%
      (33/51), mild hyponatremia was 50.98% (26/51), middle and severe hyponatremia was
      13.73% (7/51); among them, hyponatremia lasted less than 3 d in 57.58% (19/33)
      patients and >= 3 d in 42.42% (14/33) patients. Heart failure exacerbation and
      hypernatremia were not observed in patients receiving additional sodium chloride
      therapy. Hospitalization time was similar among patients with different blood
      natrium levels [average (16 +/- 12) d]. Fifty out of 51 (98%) patients discharged
      from the hospital with improved heart failure symptoms and signs. CONCLUSION:
      Supplying additional sodium chloride could rapid correct hyponatremia in heart
      failure patients with or without intravenous diuretics therapy which might
      contribute to a favorable prognosis in hospitalized heart failure patients.

PMID- 23141091
TI  - [Changes of open probability of large conductance Ca(2+)-activated K(+) channels
      in diabetic coronary smooth muscle cells of rats].
AB  - OBJECTIVE: To investigate the changes of open probability (Po) of large
      conductance Ca(2+)-activated K(+) channel (BK channel) in diabetic coronary
      smooth muscle cells and elucidate the underlying cellular electrophysiology
      mechanisms of coronary dysfunction. METHODS: Rat coronary smooth muscle cells
      were isolated from control group and diabetic group. BK single channel currents
      were recorded by patch clamp technique in inside-out configuration. Open
      probabilities were calculated and compared between two groups. After exposure to
      DHS-1, a specific BK channel activator, Po at 0.2 and 1 umol/L free Ca(2+) were
      compared between control and diabetic groups. RESULTS: In the presence of 0.2
      umol/L free Ca(2+), the Po at baseline was significantly lower in diabetic rats
      than in control rats (0.0032 +/- 0.0012 vs. 0.095 +/- 0.036, P < 0.05).
      Cytoplasmic application of DSH-1 significantly increased the Po to 0.335 +/-
      0.096 (P < 0.05 vs. baseline) in control rats, whereas DSH-1 had no effect in
      diabetic rats (Po = 0.022 +/- 0.018, P > 0.05 vs. baseline). In the presence of 1
      umol/L free Ca(2+), the Po at baseline was also significantly lower in diabetic
      rats than in control rats (0.210 +/- 0.055 vs. 0.458 +/- 0.077, P < 0.05).
      Cytoplasmic application of DHS-1 further robustly enhanced Po to 0.823 +/- 0.019
      (P < 0.05 vs. baseline) in control rats and to 0.446 +/- 0.098 in diabetic rats
      (P < 0.05 vs. baseline of diabetic rats; P < 0.05 vs. control rats with DHS-1).
      CONCLUSION: The decrease of Po of BK single channel in coronary smooth muscle
      cells may be a potential cause for coronary dysfunction in diabetic rats.

PMID- 23141092
TI  - [The effect of CD137-CD137 ligand interaction on the expression of nuclear factor
      of activated T cells c1 in apolipoprotein E-deficient mice atherosclerotic plaque
      model].
AB  - OBJECTIVE: To investigate the effects of CD137-CD137L interaction on the nuclear
      factor of activated T cells c1 (NFATc1) in apolipoprotein E knockout (ApoE(-/-))
      mice. METHODS: Atherosclerotic plaque model was produced by rapid perivascular
      carotid collar placement in ApoE(-/-) mice. In vivo, the expression of NFATc1 in
      mice plaque and lymphocytes was detected by immunohistochemical and flow
      cytometry, respectively. In vitro, the NFATc1 mRNA and protein expressions in
      cultured lymphocytes of ApoE(-/-) mice were measured by RT-PCR and flow
      cytometry, respectively. RESULTS: In vivo, after stimulating CD137-CD137L signal
      pathway, the expression of NFATc1 was significantly upregulated in the
      atherosclerotic plaques and lymphocytes. In vitro, the mRNA and protein
      expressions of NFATc1 in cultured leukocytes of ApoE(-/-) mice were also
      significantly increased, the maximal effect appeared post 20 ug/ml anti-CD137 mAb
      stimulation and reached maximum at 24 h at any concentrations. Anti-CD137L mAb
      significantly downregulated the mRNA and protein expressions of NFATc1 in
      lymphocytes of ApoE(-/-) mice, maximal effect appeared at 20 ug/ml anti-CD137L
      mAb and reached minimum at 24 h. CONCLUSION: CD137-CD137L interactions can
      modulate the expression of NFATc1 in this ApoE(-/-) mice atherosclerotic plaque
      model.

PMID- 23141093
TI  - [Activating protein kinase C enhances ventricular action potential duration
      restitution and increase arrhythmia susceptibility in Langendorff-perfused rabbit
      hearts].
AB  - OBJECTIVE: To determine effects of activating protein kinase C (PKC) on
      ventricular action potential duration restitution (APDR) and Burst stimulus
      induced arrhythmia in Langendorff-perfused rabbit hearts. METHODS: Male rabbits
      were equally divided into three groups randomly: control group (Tyrode's solution
      perfusion), PKC agonist phorbol-12-myristate-13-acetate (PMA, 100 nmol/L) group
      and PKC inhibitor bisindolylmaleimide (BIM, 500 nmol/L) group. Thirty minutes
      after perfusion, the monophasic action potential (MAP) and effective refractory
      period (ERP) were determined in right basal ventricle (RB), right apex (RA), left
      basal ventricle (LB) and left apex (LA) of all the animals, and APDR curve was
      drawn. Burst stimulus method was used to induce ventricular arrhythmia in
      perfused rabbit hearts; Real-time PCR was used to detect the mRNA expression of
      PKC in four different areas of ventricle. RESULTS: Compared with the control
      group, the ERP, 90% of monophasic action potential duration (MAPD(90)) and
      ERP/MAPD(90) were significantly shortened (all P < 0.01), the max slopes (S(max))
      of APDR curve were significantly steeper (RB: 1.22 +/- 0.23 vs. 0.65 +/- 0.19;
      RA: 2.99 +/- 0.29 vs. 1.02 +/- 0.18; LB: 1.84 +/- 0.21 vs. 0.85 +/- 0.12; LA:
      4.02 +/- 0.32 vs.1.12 +/- 0.23, all P < 0.01) and the incidences of ventricular
      arrhythmia were significantly increased in the PMA group. All parameters were
      similar between the BIM group and the control group (all P > 0.05). CONCLUSION:
      Activating PKC could enhance the max slopes of APDR curve at various ventricular
      areas and subsequently increase arrhythmia susceptibility in Langendorff-perfused
      rabbit hearts.

PMID- 23141094
TI  - [Prevalence, detection, management, and control of hypertension in the population
      of Mongolian and Han nationalities with age >= 55 years in a pastoral area of
      Inner Mongolia Autonomous Region].
AB  - OBJECTIVE: To know about the status of hypertension among Mongolian and Han aged
      older than 55 years living in pastoral area of the Inner Mongolia Autonomous
      Region. METHODS: Stratified sampling method was adopted and 9146 people aged 55
      years or older were selected, blood pressure measurement and related information
      were collected, prevalence, awareness, treatment and control rates of
      hypertension were analyzed. RESULTS: The hypertension crude prevalence rate of
      Mongolian and Han subjects was 54.10% (standardized prevalence rate was 53.93%),
      in which, the Mongolian and Han subjects crude hypertension prevalence rate was
      52.96% and 54.73% respectively (standardized prevalence rate was 53.44% and
      55.08% respectively), and there was no statistically significant (P = 0.104).
      Among the male gender, awareness rate, treatment rate and control rate of
      hypertension was 61.03%, 46.73% and 11.87% respectively. Among the female gender,
      awareness rate, treatment rate and control rate of hypertension was 67.58%,
      56.55% and 14.03% respectively. Among Mongolian and Han subjects, difference of
      hypertension prevalence of different age groups was statistically significant (P
      values were 0.032 and 0.000), Among Mongolian subjects, difference of
      hypertension awareness of different age groups was statistically significant (P =
      0.000). Among Han subjects, difference of hypertension awareness rates, treatment
      rates, and control rates of different age groups were statistically significant
      (P values were 0.000, 0.047 and 0.043). CONCLUSION: Hypertension prevalence rate
      among Han and Mongolian people older than 55 years living in pastoral area of
      Inner Mongolia Autonomous Region is high while the awareness, treatment and
      control rates of hypertension are rather low.

PMID- 23141095
TI  - [Abdominal aortic aneurysm in a patient with overlap syndrome: a case report].

PMID- 23141096
TI  - [A case report of misdiagnosis of acute myocardial infarction complicated with
      aortic dissection].

PMID- 23141097
TI  - [Stenting treatment for anomalous origin of the right coronary artery from the
      left coronary sinus: two cases report].

PMID- 23141098
TI  - [Role of calcineurin/NFATc1 signaling pathway in cardiovascular development].

PMID- 23141099
TI  - [Polymorphism of genes encoding homocysteine metabolism-related enzymes and risk
      for cardio-cerebrovascular disease].

PMID- 23141100
TI  - Estrogens and inflammatory autoimmune diseases.

PMID- 23141101
TI  - Cross-sectional associations between macronutrient intake and chronic kidney
      disease in a population at high cardiovascular risk.
AB  - BACKGROUND & AIMS: The aim was to examine the associations between macronutrient
      intake and the prevalence of chronic kidney disease (CKD) or microalbuminuria
      (MiA) in individuals at high cardiovascular risk. METHODS: Cross-sectional
      analyses conducted in 2123 nondiabetic individuals from the PREDIMED study.
      Dietary data were collected using a food-frequency questionnaire. Analysis of
      covariance was used to assess associations between quartiles of nutrient intake
      and estimated glomerular filtration rate (eGFR) or urinary albumin-to-creatinine
      ratio (ACR). The odds ratio (OR) for the presence of CKD or MiA according to
      quartiles of nutrient intake was assessed by logistic regression models. RESULTS:
      Individuals in the highest quartile of n-6 polyunsaturated fatty acid (PUFA)
      intake showed lower average eGFR. Individuals in the top quartile of fiber intake
      had a decreased risk of CKD [OR: 0.68; 95% CI: 0.48-0.95]. Conversely, subjects
      in the highest quartile of n-6 PUFA intake showed an increased risk of CKD [OR:
      1.44; 95% CI: 1.03-2.01]. No significant associations were found between the
      intake of other macronutrients and eGFR, urinary ACR or risk of CKD or MiA.
      CONCLUSIONS: A high fiber intake was associated with a decreased risk of CKD,
      while a high n-6 PUFA intake was inversely associated with eGFR and directly
      associated with an increased risk of CKD.

PMID- 23141102
TI  - The use of eschar swabs for the diagnosis of African tick-bite fever.
AB  - African tick-bite fever (ATBF) caused by Rickettsia africae is a frequent cause
      of fever in returned travelers. Here, we used eschar swabs and/or eschar crust
      samples for the molecular diagnosis of ATBF in returned travelers. In 4 of 5
      patients returning from South Africa, including 3 with negative serology, R.
      africae was identified by molecular tools targeting 2 different genes. The
      findings of this study highlight the usefulness of eschar swabs and/or eschar
      crust samples for the diagnosis of R. africae infection.

PMID- 23141103
TI  - Presence of an emerging subclone of Francisella tularensis holarctica in Ixodes
      ricinus ticks from south-western Germany.
AB  - The zoonotic disease tularaemia is caused by the bacterial pathogen Francisella
      tularensis. Although the causative agent is known for 100 years, knowledge of its
      enzootic cycles is still rudimentary. Apart from tabanids and mosquitoes, hard
      ticks have been described as important vectors and potential reservoirs for F.
      tularensis. Available data on the incidence of human tularaemia indicate an
      increase in cases in the federal state of Baden-Wuerttemberg. To determine
      whether ticks are involved in the reported increase in F. tularensis infections
      in humans and wildlife in this south-western part of Germany, 916 Ixodes ricinus
      and 211 adult Dermacentor marginatus and D. reticulatus ticks were collected in
      two different locations. Screening for the presence of F. tularensis was
      performed by real-time PCR of the 16S rRNA gene. Of the 95 pools of I. ricinus
      ticks (representing 916 individual ticks), 8 tick pools (8.4%) were positive in
      this PCR. 30-bp deletion PCR confirmed that the F. tularensis subspecies
      holarctica was present. FtM24 VNTR analysis revealed that they belong to the
      emerging Franco-Iberian subclone group of F. tularensis holarctica. Of the 211
      ticks of the genus Dermacentor, 35 randomly chosen DNAs were subjected to 16S
      rRNA gene screening PCR; 20 of these (57%) gave positive signals. For cluster
      analysis, the lpnA gene region of all Francisella-positive I. ricinus pools and 6
      Dermacentor ticks with a positive reaction in the screening PCR was amplified and
      sequenced. In the resulting neighbour-joining tree, all Francisella-positive I.
      ricinus samples clustered with sequences of F. tularensis, whilst all Dermacentor
      tick samples clustered with FLE (Francisella-like endosymbiont) sequences. This
      study shows that I. ricinus ticks may serve as vectors and/or reservoirs of F.
      tularensis in Germany and supports the hypothesis that the state of Baden
      Wuerttemberg represents an emerging endemic focus of tularaemia.

PMID- 23141104
TI  - Rickettsiae of spotted fever group, Borrelia valaisiana, and Coxiella burnetii in
      ticks on passerine birds and mammals from the Camargue in the south of France.
AB  - Ticks are obligate hematophagous arthropods that have a limited mobility, but can
      be transported over large geographical distances by wild and domestic mammals and
      birds. In this study, we analyze the presence of emerging zoonotic bacteria in
      ticks collected from passerine birds and mammals present in the Camargue, in the
      south of France, which is a major rallying point for birds migrating from Eurasia
      and Africa. The presence of Coxiella burnetii, Rickettsia, Borrelia, and
      Bartonella was examined by real-time PCR on DNA samples extracted from 118 ticks.
      Rickettsia massiliae was detected in ticks from Passer domesticus, Ri.
      aeschlimannii in ticks from Acrocephalus scirpaceus and Luscinia megarhynchos,
      and Borrelia valaisiana in one tick from Turdus merula. In addition, Ri.
      massiliae, Ri. slovaca, Candidatus Ri. barbariae, and C. burnetii were detected
      in ticks from dogs, horses, cats, and humans. No Bartonella DNA was detected in
      these samples. The migratory birds may play a role in the transmission of
      infectious diseases and contribute to the geographic distribution of Ri.
      aeschlimannii, Bo. valaisiana, and C. burnetii. The role of birds in spreading
      Rh. sanguineus ticks infected with Ri. massiliae needs to be clarified by
      complementary studies. This is the first detection of Candidatus Ri. barbariae in
      Rh. sanguineus from the south of France.

PMID- 23141105
TI  - Immunization with adenoviral-vectored tick salivary gland proteins (SALPs) in a
      murine model of Lyme borreliosis.
AB  - Prior exposure of vertebrate hosts to tick salivary proteins can induce specific
      immunity to tick infestation, as well as affording protection against tick
      transmitted Borrelia burgdorferi infection in the mammalian host. Vaccination
      using an adenovirus expression system to deliver 4 tick salivary proteins (Ad
      Salps) derived from Ixodes scapularis, Salp15, Salp25A, Salp25D, and Isac, was
      explored. Results indicate that vaccination with tick salivary proteins in an
      adenoviral vector can be used to modulate a Th1 response in the host and
      partially control spirochete load in immunized mice after infected tick
      challenge.

PMID- 23141106
TI  - Ehrlichia canis in Rhipicephalus sanguineus ticks in the Ivory Coast.
AB  - Canine monocytic ehrlichiosis caused by Ehrlichia canis is distributed globally,
      but its prevalence in Africa is poorly known. In the study reported herein, 27%
      of Rhipicephalus sanguineus ticks collected from watchdogs in Abidjan, Ivory
      Coast, were positive for E. canis using quantitative real-time PCR. A new
      molecular strategy is proposed that can be used not only for epidemiological
      study, but also for the diagnosis of canine monocytic ehrlichiosis. Our findings
      show for the first time the presence of E. canis using molecular tools in the
      Ivory Coast, providing direct evidence for the presence of this pathogen.

PMID- 23141107
TI  - Detection of Rickettsia helvetica in Ixodes ricinus ticks collected from Pyrenean
      chamois in France.
AB  - Seventy-one Ixodes ricinus ticks collected from Pyrenean chamois (Rupicapra
      pyrenaica) in the French Pyrenees were tested by real-time polymerase chain
      reaction to detect the presence of Rickettsia and Bartonella. Four ticks (6%)
      were positive for R. helvetica. The chamois carries infected ticks, and this
      enables the dissemination throughout the environment with this bacterium, a
      potential human pathogen.

PMID- 23141109
TI  - Gut microbiota and kin recognition.
AB  - The animal gut contains a large reservoir of symbionts. Whilst these microbes
      have obvious physiological functions in, for example, digestion and immune
      defence, they can also affect their host's behavior. Increasing evidence suggests
      that gut microbiota alters the scent of an individual, thereby affecting mate
      choice and kin recognition.

PMID- 23141108
TI  - miR-786 regulation of a fatty-acid elongase contributes to rhythmic calcium-wave
      initiation in C. elegans.
AB  - BACKGROUND: Rhythmic behaviors are ubiquitous phenomena in animals. In C.
      elegans, defecation is an ultradian rhythmic behavior: every ~50 s a calcium wave
      initiating in the posterior intestinal cells triggers the defecation motor
      program that comprises three sequential muscle contractions. Oscillatory calcium
      signaling is central to the periodicity of defecation. The posteriormost
      intestinal cells function as the pacemaker for this rhythmic behavior, although
      it is unclear how the supremacy of these cells for calcium-wave initiation is
      controlled. RESULTS: We describe how the loss of the mir-240/786 microRNA
      cluster, which results in arrhythmic defecation, causes ectopic intestinal
      calcium-wave initiation. mir-240/786 expression in the intestine is restricted to
      the posterior cells that function as the defecation pacemaker. Genetic data
      indicate that mir-240/786 functions upstream of the inositol 1,4,5-trisphosphate
      (IP(3)) receptor. Through rescue analysis, it was determined that miR-786
      functions to regulate defecation. Furthermore, we identified elo-2, a fatty-acid
      elongase with a known role in defecation cycling, as a direct target for miR-786.
      We propose that the regulation of palmitate levels through repression of elo-2
      activity is the likely mechanistic link to defecation. CONCLUSIONS: Together,
      these data indicate that miR-786 confers pacemaker status on posterior intestinal
      cells for the control of calcium-wave initiation through the regulation of elo-2
      and, subsequently, palmitate levels. We propose that a difference in fatty-acid
      composition in the posterior intestinal cells may alter the activities of
      membrane proteins, such as IP(3)-receptor or TRPM channels, that control
      pacemaker activity in the C. elegans intestine.

PMID- 23141110
TI  - Evolutionary divergence in acoustic signals: causes and consequences.
AB  - Acoustic signals mediate mate choice, resource defense, and species recognition
      in a broad range of taxa. It has been proposed, therefore, that divergence in
      acoustic signals plays a key role in speciation. Nonetheless, the processes
      driving divergence of acoustic traits and their consequences in terms of
      speciation are poorly understood. A review of empirical and comparative studies
      reveals strong support for a role of sexual selection in acoustic divergence, but
      the possible concomitant influences of ecological context are rarely examined. We
      summarize a conceptual framework for testing the relative significance of both
      adaptive and neutral mechanisms leading to acoustic divergence, predictions for
      cases where these processes lead to speciation, and how their relative importance
      plays out over evolutionary time.

PMID- 23141111
TI  - Prevention and surveillance of public health risks during extended mass
      gatherings in rural areas: the experience of the Tamworth Country Music Festival,
      Australia.
AB  - OBJECTIVE: To describe and evaluate the public health response to the Tamworth
      Country Music Festival, an annual extended mass gathering in rural New South
      Wales, Australia; and to propose a framework for responding to similar rural mass
      gatherings. STUDY DESIGN: Process evaluation by direct observation, archival
      analysis and focus group discussion. METHODS: The various components of the
      public health response to the 2011 Tamworth Country Music Festival were actively
      recorded. An archival review of documentation from 2007 to 2010 was performed to
      provide context. A focus group was also conducted to discuss the evolution of the
      public health response and the consequences of public health involvement.
      RESULTS: Public health risks increased with increasing duration of the rural mass
      gathering. Major events held within the rural mass gathering further strained
      resources. The prevention, preparedness, response and recovery principles
      provided a useful framework for public health actions. Particular risks included
      inadequately trained food preparation volunteers functioning in poorly equipped
      temporary facilities, heat-related ailments and arboviral disease. CONCLUSION:
      Extended mass gatherings in rural areas pose particular public health challenges;
      surge capacity is limited and local infrastructure may be overwhelmed in the
      event of an acute incident or outbreak. There is value in proactive public health
      surveillance and monitoring. Annual mass gatherings provide opportunities for
      continual systems improvement. Early multi-agency planning can identify key risks
      and identify opportunities for partnership. Special consideration is required for
      major events within mass gatherings.

PMID- 23141112
TI  - Keeping a weather eye on things.

PMID- 23141113
TI  - Biological evaluation of novel substituted chloroquinolines targeting
      mycobacterial ATP synthase.
AB  - The ATP synthase of Mycobacterium tuberculosis is a validated drug target against
      which a diarylquinoline drug is under clinical trials. The enzyme is crucial for
      the viability both of actively replicating and non-replicating/dormant M.
      tuberculosis. Enzyme levels drop drastically as the bacilli enter dormancy and
      hence an inhibitor would make the dormant bacilli even more vulnerable. In this
      study, a set of 18 novel substituted chloroquinolines were screened against
      Mycobacterium smegmatis ATP synthase; 6 compounds with the lowest 50% inhibitory
      concentration (IC(50)) values (0.36-1.83 MUM) were selected for further in vitro
      studies. All six compounds inhibited the growth of M. tuberculosis H37Rv in
      vitro, with minimum inhibitory concentrations (MICs) of 3.12 MUg/mL (two
      compounds) or 6.25 MUg/mL (four compounds). All of them were bactericidal to non
      replicating M. tuberculosis H37Rv in hypoxic culture; three compounds caused a >2
      log(10) reduction in CFU counts in 4 days at concentrations of 16* or 32* their
      MICs, compared with a 0.2 log(10) reduction by isoniazid and a >4 log(10)
      reduction by rifampicin at 100* their MICs. The compounds also contributed to a
      greater reduction in total cellular ATP of the bacilli compared with isoniazid
      and rifampicin during an exposure time of 18 h. The compounds at 100 MUM caused
      only 5-35% inhibition of mouse liver mitochondrial ATP synthase, leading to
      selectivity indices ranging from >55-fold to >278-fold. In vitro cytotoxicity to
      the Vero cell line measured as the 50% cytotoxic concentration (CC(50)) of the
      compounds ranged between 55 MUg/mL and >300 MUg/mL.

PMID- 23141114
TI  - Activity of LL-37, CRAMP and antimicrobial peptide-derived compounds E2, E6 and
      CP26 against Mycobacterium tuberculosis.
AB  - Tuberculosis (TB) is a major worldwide health problem in part due to the lack of
      development of new treatments and the emergence of new strains such as multidrug
      resistant (MDR) and extensively drug-resistant strains that are threatening and
      impairing the control of this disease. In this study, the efficacy of natural and
      synthetic cationic antimicrobial (host defence) peptides that have been shown
      often to possess broad-spectrum antimicrobial activity was tested. The natural
      antimicrobial peptides human LL-37 and mouse CRAMP as well as synthetic peptides
      E2, E6 and CP26 were tested for their activity against Mycobacterium tuberculosis
      both in in vitro and in vivo models. The peptides had moderate antimicrobial
      activities, with minimum inhibitory concentrations ranging from 2 MUg/mL to 10
      MUg/mL. In a virulent model of M. tuberculosis lung infection, intratracheal
      therapeutic application of these peptides three times a week at doses of ca.
      1mg/kg led to significant 3-10-fold reductions in lung bacilli after 28-30 days
      of treatment. The treatments worked both against the drug-sensitive H37Rv strain
      and a MDR strain. These results indicate that antimicrobial peptides might
      constitute a novel therapy against TB.

PMID- 23141115
TI  - The effects of the catechol-O-methyltransferase val158met polymorphism on white
      matter connectivity in patients with panic disorder.
AB  - BACKGROUND: The catechol-O-methyltransferase (COMT) gene val158met polymorphism
      (rs4680) has been found to be associated with various psychiatric phenotypes
      including panic disorder. Considering the probable genetic influence of COMT on
      the pathogenesis of panic disorder and white matter connectivity, the present
      study investigated white matter connectivity using diffusion tensor imaging in
      relation to the COMT genotype in panic disorder. METHODS: Twenty-six patients
      with panic disorder and twenty-six age- and gender-matched healthy controls
      participated in this study. Brain magnetic resonance scans and genotype analysis
      for COMT rs4680 were conducted. Panic Disorder Severity Scale, Albany Panic and
      Phobia Questionnaire, and Anxiety Sensitivity Inventory-Revised were assessed.
      Tract-based spatial statistics (TBSS) were used for image analysis. RESULTS:
      There was no significant difference in white matter analysis between panic
      disorder and healthy controls. However, TBSS analysis showed increased fractional
      anisotropy (FA) in posterior thalamic radiation, posterior and superior corona
      radiata, superior longitudinal fasciculus, and sagittal stratum, all located in
      the right hemisphere in COMT AA/AG genotype group compared to GG genotype in
      panic disorder. Voxelwise correlational analysis revealed the symptom severity
      scores are correlated with the FA in white matter tracts that previously showed
      significant group differences between AA/AG and GG genotypes in COMT AA/AG
      genotype group, while no significant correlation was found in GG genotype group.
      LIMITATIONS: The sample size in each group was small, hence, further studies with
      larger numbers of patients are needed to confirm our findings. CONCLUSIONS: These
      data suggested that COMT rs4680 could affect the white matter connectivity in
      panic disorder.

PMID- 23141116
TI  - Association of angiotensin-converting enzyme inhibitor therapy initiation with a
      reduction in hemoglobin levels in patients without renal failure.
AB  - OBJECTIVE: To investigate whether treatment initiated with an angiotensin
      converting enzyme inhibitor (ACE-I) or an angiotensin II receptor blocker (ARB)
      for patients with ischemic heart disease, hypertension, or diabetes causes a
      reduction in hemoglobin (Hb) levels. PATIENTS AND METHODS: This was a
      retrospective cohort analysis using the computerized database of a large health
      maintenance organization. Included were all adults with a first purchase of an
      ACE-I, an ARB, or a calcium channel blocker (CCB) between January 1, 2004, and
      December 31, 2009, defined as the index date. Measures of Hb levels before and 1
      year after the index date were reviewed, and the change was calculated. All the
      analyses were stratified by pharmaceutical class. The main exposure variables
      were the proportion of days covered (PDC) by these drugs and the mean enalapril
      dosage (for enalapril users only). RESULTS: Levels of Hb before and after
      treatment were available for 14,754 patients taking ACE-Is, 751 taking ARBs, and
      3087 taking CCBs. A high PDC was significantly associated with greater yearly
      reductions in Hb levels compared with a low PDC for CCB use, but was more
      pronounced for ACE-I and ARB use. A high PDC was also associated with a higher
      odds of developing anemia in ACE-I users (odds ratio [OR], 1.59; P<.001) and ARB
      users (OR, 2.21; P=.05). In nonanemic enalapril users, every 10-mg increment in
      daily dose was associated with an OR of 1.45 for the development of anemia
      (P<.001). The association remained after excluding nonadherent patients.
      CONCLUSION: Levels of Hb are reduced during the first year of use of ACE-Is and
      to a lesser extent with use of ARBs. This association is dose dependent and is
      not explained by patient adherence.

PMID- 23141117
TI  - Using social media to improve continuing medical education: a survey of course
      participants.
AB  - OBJECTIVE: To determine continuing medical education (CME) course participants'
      use of social media (SM) and their attitudes about the value of SM for enhancing
      CME education and to examine associations between participants' characteristics
      and attitudes toward SM. PARTICIPANTS AND METHODS: We conducted a cross-sectional
      survey and validation study of 539 participants at a Mayo Clinic Internal
      Medicine CME course in November 2011. The Social Media Use and Perception
      Instrument (SMUPI) consisted of 10 items (5-point Likert scales) and categorical
      response options. The main outcome measures were psychometric characteristics of
      the SMUPI scale, course participants' use of SM, and their attitudes regarding
      the importance of SM for enhancing CME. RESULTS: Of 539 CME course participants,
      327 (61%) responded to the SMUPI survey. Most respondents (291 [89%]) reported
      using SM, with the most common types being YouTube (189 of the 327 participants
      [58%]) and Facebook (163 of 327 [50%]). Factor analysis revealed a 2-dimensional
      assessment of course participants' attitudes. Internal consistency reliability
      (Cronbach alpha) was excellent for factor 1 (0.94), factor 2 (0.89), and overall
      (0.94). The CME course participants' favorable attitudes toward SM were
      associated with younger age (20-29 years, mean score 3.13; 30-39 years, 3.40; 40
      49 years, 3.39; 50-59 years, 3.18; 60-69 years, 2.93; and >=70 years, 2.92;
      P=.02), using SM frequently (never, mean score 2.49; less than once monthly,
      2.75; once monthly, 3.21; weekly, 3.31; and daily, 3.81; P<.0001), and
      professional degree (PhD, mean score 3.00; MD, 3.05; DO, 3.35; PA, 3.42; and NP,
      3.50; P=.01). CONCLUSION: We describe the first validated measure of CME course
      participants' use of and attitudes toward SM. Our results suggest that CME course
      directors should guide SM strategies toward more youthful, technology-savvy CME
      participants and that SM will become increasingly worthwhile in CME as younger
      learners continue to enter the profession.

PMID- 23141118
TI  - Abdominal circumference measurement by ultrasound does not enhance estimating the
      association of visceral fat with cardiovascular risk.
AB  - OBJECTIVES: To evaluate the association between visceral fat and cardiovascular
      risk factors and to compare the ultrasonographic measurements of abdominal
      visceral fat with abdominal circumference (AC). METHODS: This observational cross
      sectional study categorized pubertal and postpubertal adolescents into a control
      group (n = 49) and an obese group (n = 46). Weight, height, AC, blood pressure,
      biochemical tests (lipid profile, triacylglycerols, fasting glucose for
      insulinemia, and serum uric acid), and ultrasound to measure visceral fat were
      assessed. RESULTS: We found significant differences in the vascular risk
      variables between the groups, except for total cholesterol and fasting blood
      glucose level. We also observed that 31 subjects in the control group presented
      abnormalities in cardiovascular risk factors. The correlations between abdominal
      visceral fat (measured by ultrasound or the AC) and cardiovascular risk factors
      were significant. In the entire sample, AC presented better sensitivity and
      specificity than the ultrasound-measured abdominal visceral fat for identifying
      the presence of a cluster of at least three cardiovascular risk factors (areas
      under the receiver operating characteristics curve 0.87 and 0.73, respectively).
      CONCLUSION: Ultrasonographic measurements of visceral fat were correlated with
      cardiovascular risk factors, but this association was also demonstrable with AC
      measurements. Our results suggest that the measurement of visceral fat by
      ultrasound is unnecessary for the diagnosis of cardiovascular risk in well
      nourished or obese adolescents.

PMID- 23141119
TI  - Successful treatment of parenteral nutrition-associated liver disease in an adult
      by use of a fish oil-based lipid source.
AB  - Liver disease occurs in 15% to 40% of adults on long-term parenteral nutrition,
      with steatosis being more common than cholestasis in the adult population. This
      problem has been well reported in the pediatric population, but we describe the
      case of a man who became profoundly jaundiced after being on parenteral nutrition
      for 3 y and responded rapidly to a change in lipid source from soybean and olive
      oil-based emulsion (ClinOleic) to a fish oil-based lipid emulsion (Omegaven).

PMID- 23141120
TI  - Effectiveness of immunonutrient-enriched diets in the decrease of infections and
      mortality in the critically ill.
AB  - OBJECTIVE: Pharmaconutrients have been shown in clinical and laboratory studies
      to modulate human and animal immune responses and thus to have potential benefits
      for the critically ill. However, reviews and meta-analyses continue to reflect
      controversy in the published research and a lack of agreement regarding these
      benefits. The objective of this study was to contribute to the resolution of such
      controversy by evaluating the effectiveness of immunonutrient-enriched diets in
      decreasing complications and mortality in patients with different critical
      illnesses. METHODS: The present study is a meta-analysis of randomized clinical
      trials that evaluated the use of immunomodulating nutrients in critically ill
      adults. The PubMed and CINAHL datasets were searched. RESULTS: Two hundred
      sixteen articles were initially found, but only 39 met the established inclusion
      criteria. In the general population, mortality did not show a statistically
      significant relative risk (RR) decrease (0.92, confidence interval [CI] 0.80
      1.05); infection complications were decreased, with a general RR of 0.57 (CI 0.44
      0.74) and an RR of 0.56 (CI 0.46-0.68) in surgical patients; and the sepsis
      incidence was decreased (RR 0.48, CI 0.27-0.83). CONCLUSIONS: The administration
      of immunomodulating nutrient-enriched diets did not change the mortality of
      critically ill or surgical patients, but infection complications in critically
      ill patients, in particular the surgical population, were decreased. Explanatory
      clinical trials using isolated immunomodulating nutrients in different
      populations of critically ill patients followed by pragmatic trials based on
      clinical trial results should be considered in future research.

PMID- 23141121
TI  - [Response from K. Morcel to the article from A. El Khamlichi et al.: Typical form
      of Mayer-Rokitansky-Kuster-Hauser syndrome and ectopic kidney. A rare
      association. Gynecol Obstet Fertil 2011;39:e40-e43].

PMID- 23141122
TI  - Glucose targets in older adults with diabetes: an evolving landscape.

PMID- 23141123
TI  - Body mass index as a predictor of all-cause mortality in nursing home residents
      during a 5-year follow-up.
AB  - BACKGROUND: Body mass index (BMI) is considered a short-term mortality predictor,
      but a consensus has not been reached on its role and that of other nutritional
      parameters in predicting long-term mortality in nursing home residents.
      OBJECTIVES: To correlate BMI, Mini Nutritional Assessment scores, and serum
      albumin levels with the 5-year mortality rate in institutionalized elderly
      subjects. METHODS: A total of 181 nursing home residents aged >= 70 years were
      included in a 5-year longitudinal study. Data were collected on all participants'
      nutritional, health, cognitive, and functional status by means of a comprehensive
      geriatric assessment. Data on the participants' vital status were obtained 5
      years after beginning the study, and a survival analysis was conducted using
      Kaplan-Meier curves and multivariate Cox proportional hazards models. RESULTS:
      The 5-year mortality rate was 63%. The deceased subjects (n = 115) had a lower
      BMI (24.7 +/- 4.6 vs 26.6 +/- 5.0 kg/m(2); P = .03) and Mini Nutritional
      Assessment score (18.6 +/- 3.7 vs 20.1 +/- 3.6; P = .02) than those still alive.
      Serum albumin levels did not differ between the two groups. Among the three
      indicators of nutritional status considered in this study, only BMI >= 30 kg/m(2)
      was significantly associated with a lower mortality risk at 5 years (hazard ratio
      = 0.432; 95% CI 0.20-0.70; P = .04), the risk for death being greater the lower
      the BMI class (log-rank test: P < .001). CONCLUSIONS: Our findings suggest that
      BMI is the best of the three parameters considered as a nutritional predictor of
      nursing home residents' mortality in the longer term, and indicate that a lower
      mortality risk coincides with a higher BMI.

PMID- 23141124
TI  - Words of wisdom. Re: Radical prostatectomy versus observation for localized
      prostate cancer.

PMID- 23141125
TI  - Words of wisdom. Re: Radical prostatectomy versus observation for localized
      prostate cancer.

PMID- 23141126
TI  - Words of wisdom. Re: Use of laptop computers connected to Internet through Wi-Fi
      decreases human sperm motility and increases sperm DNA fragmentation.

PMID- 23141127
TI  - Words of wisdom. Re: Human semen quality in the new millennium: a prospective
      cross-sectional population-based study of 4867 men.

PMID- 23141128
TI  - Words of wisdom. Re: Effects of the reduced form of coenzyme Q10 (ubiquinol) on
      semen parameters in men with idiopathic infertility: a double-blind, placebo
      controlled, randomized study.

PMID- 23141129
TI  - Words of wisdom. Re: Complex artificial urinary sphincter revision and
      reimplantation cases--how do they fare compared to virgin cases?

PMID- 23141130
TI  - [Delivery in women with previous cesarean section or other uterine surgery:
      guidelines for clinical practice - method and organization].

PMID- 23141131
TI  - [Information and facilities recommendations concerning trial of labour in the
      context of scarred womb].
AB  - OBJECTIVES: To precise key elements concerning facilities and patient information
      prior to trial of labour in the context of scarred womb. METHOD: Bibliographic
      search restricted to French and English languages using Medline database and
      recommendations of medical societies. RESULTS: Only expert's opinions are
      available. Patient information should present both trial of labour and elective
      cesarean section. Counselling should be influenced by individual risk of failed
      vaginal birth and uterine rupture. Mode of delivery should be planned the latest
      at 8 months of gestation. Patient should be aware of obstetrical and anesthetic
      facilities. Trial of labour should be presented as the first option for patients
      with no additional risk factors. Immediate presence of obstetrician and
      anesthesiologist is not required except in the context of increased risk for
      failed trial of labour or uterine rupture. Elective cesarean section on maternal
      request is acceptable after extensive counselling and delay of reflexion.
      CONCLUSION: Individual patient information should be initiated early and mode of
      delivery should be planned at 8 months of gestation. Resources and facilities
      recommendations aim to facilitate prompt cesarean section.

PMID- 23141132
TI  - [Management of post-partum infections].
AB  - Post-partum endometritis are frequent and account for the fifth cause of maternal
      death. This disease is preventable and effective treatments are available.
      Streptococcus agalactiae is the primary pathogen implicated. The clinical
      diagnosis is usually easy and involves pelvic pain, fever and abnormal lochia.
      Whenever antibiotic treatment provides no clinical improvement, or in case of
      doubt on the vacuity of the uterus, an ultrasound exam must be performed.
      Likewise, a CT scan or a MRI will be performed in case of persistent fever in
      search of a pelvic abscess requiring a drainage, or of a pelvic thrombophlebitis.
      Thromboplebitis requires heparin for the duration of antibiotic therapy, or oral
      anticoagulants for at least 3 months in case of pulmonary embolism or extension
      to the vena cava. The recommended antibiotic regimen combines clindamycin with
      gentamicin (once daily) intravenously. In case of contraindication or
      breastfeeding, other regimens may be prescribed. Adequate duration of treatment
      has not been evaluated and a switch to oral antibiotics after clinical
      improvement brings no benefit. Antibioprophylaxy (mostly cephalosporins) is
      recommended in cases of cesarean section (at skin incision), while it is debated
      in case of assisted delivery or of 3rd and 4th degree perineal tears.

PMID- 23141133
TI  - [Benefits and harms to the newborn of maternal attempt at trial of labor after
      prior caesarean versus elective repeat caesarean delivery].
AB  - OBJECTIVE: To evaluate neonatal outcome after elective repeat cesarean delivery
      (ERCD) versus trial of labor (TOL) after previous cesarean delivery. METHODS:
      This systematic evidence review is based on Pubmed search, Cochrane library and
      experts recommendations. RESULTS: The risks of fetal, perinatal and neonatal
      mortality are low after previous cesarean delivery but significantly higher for
      TOL as compared with ERCD. The risk of bag-and-mask ventilation and intubation
      for meconium-stained amniotic fluid are higher for TOL as compared with ERCD.
      Infants born after ERCD are more likely presented transient tachypnea. The risk
      of hypoxic encephalopathy/asphyxia is low after previous cesarean delivery but
      significantly higher for TOL as compared with ERCD. The risk of neonatal sepsis
      after previous cesarean delivery is significantly higher for TOL as compared with
      ERCD. There is no significant difference between TOL or ERCD regarding NICU
      admission. The strength of evidence is low to conclude about the impact of route
      of delivery upon birth trauma and Apgar score. CONCLUSIONS: The risk of the main
      neonatal complications is low whatever the route of delivery after previous
      caesarean delivery. However, the risk of perinatal mortality, bag-and-mask
      ventilation, perinatal asphyxia, is higher after TOL compared with ERCD. The risk
      of transient tachypnea is higher after ERCD compared with TOL.

PMID- 23141134
TI  - Towards a description of particulate fouling: from single particle deposition to
      clogging.
AB  - Particulate fouling generally arises from the continuous deposition of colloidal
      particles on initially clean surfaces, a process which can even lead to a
      complete blockage of the fluid cross-section. In the present paper, the initial
      stages of the fouling process (which include single-particle deposition and
      reentrainment) are first addressed and current modelling state-of-the-art for
      particle-turbulence and particle-wall interactions is presented. Then, attention
      is specifically focused on the later stages (which include multilayer formation,
      clogging and blockage). A detailed review of experimental works brings out the
      essential mechanisms occurring during these later stages: as for the initial
      stages, it is found that clogging results from the competition between particle
      fluid, particle-surface and particle-particle interactions. Numerical models that
      have been proposed to reproduce the later stages of fouling are then assessed and
      a new Lagrangian stochastic approach to clogging in industrial cases is detailed.
      These models further confirm that, depending on hydrodynamical conditions (the
      flow velocity), fluid characteristics (such as the ionic strength) as well as
      particle and substrate properties (such as zeta potentials), particle deposition
      can lead to the formation of either a single monolayer or multilayers. The
      present paper outlines also future numerical developments and experimental works
      that are needed to complete our understanding of the later stages of the fouling
      process.

PMID- 23141135
TI  - Substitute care entry: the relationship between race or ethnicity and levels of
      county organization.
AB  - OBJECTIVE: Past studies demonstrate a relationship between race and the
      likelihood of children entering state custody subsequent to a maltreatment
      investigation. Research also shows that community structural characteristics such
      as poverty and residential mobility are correlated with entry rates. The combined
      effect, however, of race and community characteristics on substitute care entry
      is unclear. We analyzed 3 years of Illinois child welfare administrative and
      county-level structural data to assess the combined effect of child
      characteristics and level of community organization on substitute care entry.
      METHODS: Based on county indicators of crime, socioeconomic status, residential
      mobility, and child care burden, a latent profile analysis classified Illinois
      counties into three levels of social organization (high, moderate, and low). To
      test the relationship between community and child level predictors of substitute
      care entry, a dichotomous variable representing substitute care entry was
      regressed onto county level and individual covariates (child age, race or
      ethnicity, gender, and allegation). To test the combined relationship of
      community and individual level characteristics, interactions between county level
      of organization and race were explored. RESULTS: Like previous studies, results
      showed that individual factors of race, age, and allegation were associated with
      the decision to place children in substitute care. Also consistent with past
      research, they revealed a general trend in which decreasing levels of social
      organization were associated with relatively higher odds of entry to care. The
      magnitude of this effect at each level of social organization, however, varied by
      race, with African American children in disorganized communities experiencing the
      greatest risk of removal. CONCLUSIONS: These findings suggest that efforts to
      understand the decision to place a child in substitute care may need to be
      community specific. In particular the level of community organization may
      influence the response of the system to maltreatment investigations. In
      communities with different characteristics and across racial groups, child
      welfare systems may need to examine decision making processes regarding
      children's removal from parental care.

PMID- 23141136
TI  - Does breast tumor heterogeneity necessitate further immunohistochemical staining
      on surgical specimens?
AB  - BACKGROUND: Prognostic and predictive tumor markers in breast cancer are most
      commonly performed on core needle biopsies (CNB) of the primary tumor. Because
      treatment recommendations are influenced by these markers, it is imperative to
      verify strong concordance between tumor markers on CNB specimens and the
      corresponding surgical specimens (SS). STUDY DESIGN: A prospective study was
      performed on 165 women (205 samples) with breast cancer diagnosed from January
      2009 to July 2011. Tumor type, grade, estrogen receptor (ER), progesterone
      receptor (PR), human epidermal growth factor 2 (HER2), and Ki67 expression by
      immunohistochemical (IHC) testing were retrospectively analyzed in the CNB and
      SS. Contingency tables and agreement modeling were performed. RESULTS: There was
      substantial agreement between the CNB and SS for PR% and HER2; moderate agreement
      for tumor type, grade, and ER%; and fair agreement for Ki67%. In 8% of patients
      (n = 13), tumor heterogeneity was seen. In heterogeneous tumors the overall
      concordance between the CNB and SS was worse, especially for HER2. Six of these
      patients had areas of tumor that were positive for HER2, which were not detected
      in their CNBs. Nine patients had multiple distinct molecular subtypes within
      their tumor(s). CONCLUSIONS: The heterogeneous distribution of antigens in breast
      cancer tumors raises concern that the CNB may not adequately represent the true
      biologic profile in all patients. There is strong concordance for tumor type, ER,
      and PR between CNB and SS (although a quantitative decline was noted from CNB to
      SS); however, HER2 activity does not appear to be adequately detected on CNB in
      patients with heterogeneous tumors. These data suggest that IHC testing on the
      CNB alone may not be adequate to tailor targeted therapy in all patients.

PMID- 23141137
TI  - Primary prevention of pediatric abusive head trauma: a cost audit and cost
      utility analysis.
AB  - OBJECTIVES: To obtain comprehensive, reliable data on the direct cost of
      pediatric abusive head trauma in New Zealand, and to use this data to evaluate
      the possible cost-benefit of a national primary prevention program. METHODS: A 5
      year cohort of infants with abusive head trauma admitted to hospital in Auckland,
      New Zealand was reviewed. We determined the direct costs of hospital care (from
      hospital and Ministry of Health financial records), community rehabilitation
      (from the Accident Compensation Corporation), special education (from the
      Ministry of Education), investigation and child protection (from the Police and
      Child Protective Services), criminal trials (from the Police, prosecution and
      defence), punishment of offenders (from the Department of Corrections) and life
      time care for moderate or severe disability (from the Accident Compensation
      Corporation). Analysis of the possible cost-utility of a national primary
      prevention program was undertaken, using the costs established in our cohort,
      recent New Zealand national data on the incidence of pediatric abusive head
      trauma, international data on quality of life after head trauma, and published
      international literature on prevention programs. RESULTS: There were 52 cases of
      abusive head trauma in the sample. Hospital costs totaled $NZ2,433,340, child
      protection $NZ1,560,123, police investigation $NZ1,842,237, criminal trials
      $NZ3,214,020, punishment of offenders $NZ4,411,852 and community rehabilitation
      $NZ2,895,848. Projected education costs for disabled survivors were $NZ2,452,148,
      and the cost of projected lifetime care was $NZ33,624,297. Total costs were
      $NZ52,433,864, averaging $NZ1,008,344 per child. Cost-utility analysis resulted
      in a strongly positive economic argument for primary prevention, with expected
      case scenarios showing lowered net costs with improved health outcomes.
      CONCLUSIONS: Pediatric abusive head trauma is very expensive, and on a
      conservative estimate the costs of acute hospitalization represent no more than
      4% of lifetime direct costs. If shaken baby prevention programs are effective,
      there is likely to be a strong economic argument for their implementation. This
      study also provides robust data for future cost-benefit analysis in the field of
      abusive head trauma prevention.

PMID- 23141138
TI  - New vision for contraceptive research and development.

PMID- 23141139
TI  - An editorial dedication to bicoastal mentorship.

PMID- 23141140
TI  - Gender, relationship type and contraceptive use at first intercourse.
AB  - BACKGROUND: Most of the sexually transmitted infection prevention programs fail
      to attend to the relationship type of individuals at first sexual intercourse and
      how it influences contraceptive behavior. STUDY DESIGN: A national sample of
      adolescents (3084 females and 2745 for males) was analyzed to determine the
      associations between relationship types (committed, going steady and casual), use
      of contraception and methods of contraception at first intercourse using logistic
      and multinomial logistic regressions. RESULTS: Two thirds of females and over
      three quarters of males used a condom at first intercourse while reported use of
      dual methods was 12.7% and 14.0%, respectively, for females and males at first
      intercourse. Bivariate and multivariate analyses confirmed that relationship type
      was associated with contraceptive use at first intercourse. Males in casual
      relationships had low odds (0.586) of using any method of contraception at first
      intercourse. Among contraceptive users, females in committed relationships had
      high odds (5.016) of using hormonal methods at first intercourse while males in
      casual relationships had low odds (0.379) of using dual methods at first
      intercourse. CONCLUSION: The results suggest that adolescents are at sexual
      health risk when first sexual relationship types are taken into account. Sexual
      health programs must focus on enhancing communication skills among adolescents so
      that regardless of relationship type, correct contraceptive behavior is
      practiced.

PMID- 23141141
TI  - Observer-based Hinfinity control of a class of mixed delay systems with random
      data losses and stochastic nonlinearities.
AB  - This paper investigates the observer-based Hinfinity control problem for a class
      of discrete-time mixed delay systems with random communication packet losses and
      stochastic nonlinearities. The mixed delays comprise both discrete time-varying
      and distributed delays, the random data losses are described by a Bernoulli
      distributed white sequence that obeys a conditional probability distribution, and
      the stochastic nonlinearities in the form of statistical means cover several well
      studied nonlinear functions. In the presence of mixed delays, random packet
      losses and stochastic nonlinearities, sufficient conditions for the existence of
      an observer-based feedback controller are derived, such that the closed-loop
      control system is asymptotically mean-square stable and preserves a guaranteed
      Hinfinity performance.

PMID- 23141142
TI  - Tumour necrosis factor alpha down-regulates the expression of peroxisome
      proliferator activated receptor alpha (PPARalpha) in human hepatocarcinoma HepG2
      cells by activation of NF-kappaB pathway.
AB  - Peroxisome proliferator activated receptor-alpha (PPARalpha) plays a major role
      in the regulation of lipid and glucose homeostasis, and inflammatory responses.
      The objectives of the study were to systematically investigate the effects of TNF
      alpha and its regulatory pathway on PPARalpha expression in HepG2 cells using
      Real-Time RT-PCR and western blot analysis. Here, TNF-alpha suppressed PPARalpha
      mRNA expression in a dose- and time-dependent manner at the level of gene
      transcription. Pre-treatment of cells with 10MUM of Wedelolactone for 2h was
      sufficient to restore PPARalpha expression to basal levels and also affected the
      expression of PPARalpha-regulated genes. This study also demonstrated that TNF
      alpha represses PPARalpha expression by augmenting the activity of canonical NF
      kappaB signalling pathway. This was shown by the abrogation of TNF-alpha-mediated
      PPARalpha down-regulation, after both p65 and p50 were knocked down via siRNA.
      The IKK contributes to IkappaBalpha degradation and mediates inducible
      phosphorylation of p105 at Ser933. Surprisingly, phosphorylation of p65 at Ser468
      and Ser536 were severely abrogated with Wedelolactone inhibition, suggesting that
      Ser468 and Ser536, but not Ser276, may mediate the TNF-alpha inhibitory action on
      PPARalpha gene expression. These results suggest that TNF-alpha might, at least
      in part, suppress PPARalpha expression through activation of IKK/p50/p105/p65
      pathway. Furthermore, phosphorylation of p65 at Ser468 and Ser536 may play a
      crucial role in the mechanism that limits PPARalpha production in the human HepG2
      cells.

PMID- 23141143
TI  - Interleukin-10 activates Toll-like receptor 4 and requires MyD88 for
      cardiomyocyte survival.
AB  - Toll-like receptors (TLRs) are important in a variety of inflammatory diseases
      including acute cardiac disorders. TLR4 innate signaling regulates the synthesis
      of anti-inflammatory cytokine, interleukin-10 (IL-10) upon TLR4 agonists' re
      stimulation. Anti-apoptotic action of IL-10 in cardiac dysfunction is generally
      accepted but its protective mechanism through TLR4 is not yet understood. We
      studied the effect of IL-10 in the activation of TLR4 downstream signals leading
      to cardiomyocytes survival. IL-10 caused a significant increase in the expression
      of CD14, MyD88 and TLR4. TLR4 activation led to the translocation of the
      interferon regulatory factor 3 (IRF3) into the nucleus. Phosphorylation of IRF3
      enhanced mRNA synthesis for IL-1beta but not TNF-alpha and was elevated even
      after removal of IL-10 stimulation. Furthermore, degradation of inhibitory kappa
      B (IkappaB) kinase (Ikk) suggested that IkappaBbeta was the main activating
      kinase for IRF3-regulated NF-kappaB activation and phosphorylation of p65.
      Phosphorylated NF-kappaB p65 was translocated into the nucleus. Concomitantly, an
      increase in Bcl-xL activity inhibited Bax and the proteolytic activity of caspase
      3 as well as a decrease in PARP cleavage. An inhibition of MyD88, modulated the
      above listed responses to IL-10 as there was a decrease in TLR4 and IRF3 and an
      increase in TNF-alpha mRNA. This was associated with a decrease in NF-kappaB p65,
      Bcl-xL mRNA and protein levels as well as there was an activation of Bax and PARP
      cleavage independent of caspase 3 activation. These data in cardiomyocytes
      suggest that IL-10 induced anti-apoptotic signaling involves upregulation of TLR4
      through MyD88 activation.

PMID- 23141145
TI  - Seizure-free after surgery in a patient with non-lesional startle epilepsy: a
      case report.
AB  - We present the case of a patient with startle epilepsy provoked by auditory,
      somatosensory and visual stimuli during video-electrocorticography (ECoG)
      recording. Ictal ECoG of all types of seizures triggered by the three kinds of
      stimuli showed that seizure onset originated from the left supplementary
      sensorimotor area (SSMA). The patient has been seizure-free after the cortex
      around the left SSMA only had been resected. Therefore, we speculate that left
      SSMA is the epileptogenic zone of startle epilepsy in this patient and perhaps
      the primary cortex to modulate the startle reflex in healthy persons.

PMID- 23141146
TI  - Guest editorial: health protection and communicable disease control in Hong Kong,
      China.

PMID- 23141144
TI  - Long-term safety and efficacy of clobazam for Lennox-Gastaut syndrome: interim
      results of an open-label extension study.
AB  - In an ongoing open-label extension (OV-1004), patients with Lennox-Gastaut
      syndrome who had completed 1 of 2 randomized controlled trials (OV-1002 [Phase
      II] or OV-1012 [Phase III]) are receiving clobazam at dosages <=2.0 mg/kg/day
      (<=80 mg/day). Of 306 eligible patients from OV-1002 or OV-1012, 267 entered the
      open-label extension. As of the interim date, July 1, 2010, 213 patients (79.8%)
      had remained in the trial, and 189 had received clobazam for >=12 months, 128 for
      >=18 months, and 94 for >=24 months. Median percentage decreases in average
      weekly rates of drop seizures were 71.1% and 91.6% at Months 3 and 24. Mean modal
      and mean maximum daily dosages were 0.94 mg/kg and 1.22 mg/kg for those who had
      received clobazam for >=1 year. The 4 most common adverse events were upper
      respiratory tract infection (18.4%), fall (14.2%), pneumonia (13.9%), and
      somnolence (12.7%). Clobazam's adverse event profile was consistent with its
      profile in controlled trials.

PMID- 23141147
TI  - Smoking behaviour, former quit attempts and intention to quit in urban
      adolescents and young adults: a five-year longitudinal study.
AB  - OBJECTIVES: To examine smoking behaviour, former quit attempts and intention to
      quit among Swiss adolescents and young adults over five year's time. STUDY
      DESIGN: five-year longitudinal study (2003, 2005 and 2008) based on a random
      urban community sample (N = 1345 complete cases). METHODS: Data were collected by
      computer-assisted telephone interviews with adolescents (16-17) and young adults
      (18-24). Main outcome measures included self-reported smoking behaviour, former
      quit attempts, smoking cessation methods and current intentions to quit smoking.
      RESULTS: Adolescents were more often non-smokers and less often daily smokers
      when compared to young adults at baseline (chi(2)(4) = 28.68, P < .001). Their
      smoking behaviour increased significantly from baseline to follow-up (T =
      1445.50, r = .20, P < .001) in contrast to the stable smoking behaviour in young
      adults (chi(2)(2) = .12, n.s.). In longitudinal analyses young adults were also
      more stable in their smoking status at the later measurement points. In
      comparison adolescents changed their smoking status more often being non-smokers
      at baseline and smokers later on. Independently of the age group, the majority of
      smokers already had previously attempted to quit (65%) or intended to give up
      smoking at some point (72%). However only 17% were motivated to make the quit
      attempt within the next 6 months. Self-quitting was the preferred method, and 25%
      of the self-quitters had been successful. CONCLUSION: This study illustrates that
      different developments in smoking behaviour exist in adolescents and young
      adults. Our study reveals that a majority of smokers are willing to quit but
      often fail. Furthermore, the data indicates that for adolescents the focus should
      lie on primary prevention.

PMID- 23141148
TI  - Exploring predictors influencing intended and actual acceptability of the A/H1N1
      pandemic vaccine: a cohort study of university students in Hong Kong.
AB  - OBJECTIVES: To investigate the factors associated with the uptake of influenza
      A/H1N1 vaccination by university students, and to examine the relationship
      between intention and actual vaccination. STUDY DESIGN: Prospective cohort study.
      METHODS: A baseline survey was conducted among students at the Chinese University
      of Hong Kong in 2009 to collect data on demographics, pandemic risk perceptions
      and self-reported intention to be vaccinated in the future. A follow-up survey
      was conducted in 2011 using an online survey platform collecting information on
      actual vaccine uptake behaviour, and vaccine attitudes, knowledge and
      perceptions. RESULTS: Self-reported intention to be vaccinated in 2009 was
      significantly associated with actual vaccine acceptance. Vaccine perceptions
      (attitudes and knowledge) were found to be a better predictor of vaccine
      acceptance than disease risk perceptions. Being a medical or science student and
      receiving health advice about vaccination from a doctor or school-endorsed
      advertisement were also found to be predictors of vaccine acceptance.
      CONCLUSIONS: University students in Hong Kong were wary of the A/H1N1 vaccination
      campaign, as revealed by their low uptake rate and doubts about the vaccine.
      Knowledge of the pandemic and vaccine was high in this population, but feelings
      of susceptibility were low. The results indicate a need to provide tailored
      messages emphasizing the importance of vaccination and the efficacy of the
      vaccine in the future.

PMID- 23141149
TI  - Prevalence of Staphylococcus aureus colonization and antibiotic susceptibility: a
      survey among biomedical students.

PMID- 23141150
TI  - Lenalidomide plus melphalan without prednisone for previously untreated older
      patients with multiple myeloma: a phase II trial.
AB  - BACKGROUND: We conducted a phase II trial that evaluated the tolerability and
      efficacy of combining lenalidomide with melphalan in previously untreated
      patients with multiple myeloma who were not candidates for autologous stem cell
      transplantation. METHODS: After a run-in phase of 6 patients, we planned to
      conduct a randomized phase II selection-design trial that assessed 2 dose levels
      of lenalidomide, given days 1 to 21, combined with melphalan, given days 1 to 4,
      and every 28 days. Planned doses of melphalan were 9 mg/m(2)/d and respective
      doses of lenalidomide were 10 and 20 mg/d (M9L10 and M9L20). Coprimary endpoints
      were the frequency of dose-limiting Planned doses of melphalan were 9 mg/m(2)/d
      and respective doses of lenalidomide were 10 and 20 mg/d (M9L10 and M9L20).
      toxicities (DLT) and complete response (CR). RESULTS: Four patients received
      M9L10; all experienced DLTs, which resulted in closure of this cohort. When using
      the same schedule, we then sequentially tested M6L10 (melphalan 6 mg/m(2) on days
      1 to 4 and lenalidomide 10 mg/d on days 1 to 21 every 28 days) (6 patients),
      M4L15 (melphalan 4 mg/m(2) on days 1 to 4 and lenalidomide 15 mg/d on days 1 to
      21 every 28 days) (6 patients), and M5L10 (melphalan 5 mg/m(2) days 1 to 4 and
      lenalidomide 10 mg/d days 1 to 21 every 28 days) (34 patients). In each cohort,
      the DLT endpoint was reached because of severe and prolonged hematologic
      toxicity. At the final dose level, M5L10, 20 of 27 patients experienced DLTs
      within their first 3 cycles; among 10 patients who received at least 6 cycles,
      none achieved a CR. CONCLUSIONS: Combining lenalidomide plus melphalan without
      prednisone is associated with substantial hematologic toxicity that precludes
      cyclical administration of adequate drug doses.

PMID- 23141151
TI  - An evaluation of preferred lip positions according to different age groups.
AB  - The purpose of this study was to compare preferred facial profiles rated by
      different age groups. An average profile of each gender was constructed from
      subjects with normal occlusions. Each average profile was located in the centre,
      and then the lips were protruded or retruded in six 1mm increments in each
      direction. 70 lay people were divided into 3 groups: young adult (20-39 years);
      middle-aged (40-54 years); and senior (55-70 years). They were asked to rank
      their 3 most preferred profiles for each gender. The distribution of the most
      pleasing profile was compared according to age groups by the Kruskal-Wallis test
      and according to the rater's gender by the Mann-Whitney U-test. There was a
      significant difference between the three age groups regarding the preferred male
      and female profiles (P<0.001). Both the middle-aged and the senior groups tended
      to select a slightly more retruded lip/flat profile than the young adult group.
      There was no gender dimorphism in the selection of the preferred profile. The
      young adult group preferred the straight profile while the middle-aged and senior
      groups favoured the slightly retruded profile. This may provide useful
      information for treatment planning in orthodontics and orthognathic surgery.

PMID- 23141152
TI  - Effect of modafinil on impulsivity and relapse in alcohol dependent patients: a
      randomized, placebo-controlled trial.
AB  - Poor impulse control plays an important role in the development, course and
      relapse of substance use disorders. Therefore, improving impulse control may
      represent a promising approach in the treatment of alcohol dependence. This study
      aimed to test the effect of modafinil on impulse control and alcohol use in
      alcohol dependent patients (ADP) in a randomized, double-blind, placebo
      controlled trial. Eighty-three abstinent ADP were randomized to 10 weeks
      modafinil (300 mg/d) or placebo. Alcohol use was quantified using the timeline
      follow-back method and was assessed until 6 months after treatment
      discontinuation. Impulsivity was assessed using self-report questionnaires
      (Barratt Impulsiveness Scale; State Impulsivity questionnaire) and neurocognitive
      tasks (Stop Signal Task; Delay Discounting Task) administered before, during and
      after treatment. Modafinil significantly improved self-report measures of state
      impulsivity, but had no effect on percentage of abstinent days or percentage of
      heavy drinking days, nor on the behavioral measures of impulsivity. However,
      subgroup analysis revealed that modafinil prolonged the time to relapse (p=.022)
      and tended to increase the percentage of abstinent days (p=.066) in ADP with poor
      response inhibition at baseline, whereas modafinil increased the percentage of
      heavy drinking days (p=.003) and reduced the percentage of abstinent days
      (p=.002) in patients with better baseline response inhibition. Overall results do
      not favor the use of modafinil in order to reduce relapse or relapse severity in
      ADP, and caution is required in prescribing modafinil to a non-selected sample of
      ADP. Further research on the effect of modafinil in ADP with poor baseline
      response inhibition is warranted.

PMID- 23141154
TI  - [The present status of surgical treatment for female stress urinary
      incontinence].

PMID- 23141153
TI  - Decreased default network connectivity is associated with early life stress in
      medication-free healthy adults.
AB  - Early life stress (ELS) is a significant risk factor for psychopathology,
      although there are few functional imaging studies investigating its effects.
      Previous literature suggests that ELS is associated with changes in structure and
      function in the medial prefrontal cortex (MPFC), which forms the main anterior
      node of the default network (DN). This study investigated the impact of ELS
      history on resting state DN connectivity, using seed-based correlation analyses
      (SCA) involving the posterior cingulate cortex (PCC). Data were analyzed from 22
      adult subjects without psychiatric or medical illness (13 with and 9 without
      ELS); none were taking psychotropic medication. Relative to controls, the ELS
      group had significant decreases in DN connectivity, observed between the PCC seed
      and the MPFC and inferior temporal cortex. Further analyses revealed a trend
      level increase in connectivity between the amygdala and MPFC associated with ELS
      history. In conclusion, this study found that subjects with ELS, in the absence
      of psychiatric illness and medication exposure, demonstrated decreased DN
      connectivity, and trend-level increases in connectivity between the amygdala and
      MPFC. These findings suggest that altered resting state connectivity is a
      correlate of stress exposure, rather than a product of medication or psychiatric
      morbidity.

PMID- 23141155
TI  - [Synopsis of the fourth national seminar on gynecological pelvisology].

PMID- 23141156
TI  - [Clinical study on silicone pessary in the treatment of pelvic organ prolapse].
AB  - OBJECTIVE: To evaluate the therapeutic effect and influence factors of silicone
      pessary in treatment of pelvic organ prolapse (POP). METHODS: From October 2005
      to October 2010, 132 with symptomatic POP managed by pessary were enrolled in
      this retrospective study. Validated prolapse quality of life questionnaire
      (pelvic floor distress inventory short form 20, PFDI-20), pelvic floor impact
      questionnaire short form 7 (PFIQ-7) and the patients' satisfaction degree were
      used to evaluate the therapeutic effect. Clinical characteristic of the patients
      with successful using for more than 6 months (successful fitting group), giving
      up within 6 months (giving up group), unsuccessful fitting (unsuccessful fitting
      group) were compared. Factors influencing satisfaction degree and causing
      discontinuation were investigated. RESULTS: One hundred and six among 132
      (106/132, 80.3%) patients were in successful fitting group, 26 (26/132, 19.7%)
      patients were in the unsuccessful fitting group. In the successful fitting group,
      86.8% (92/106) patients were followed up, the median follow-up time was 12.5
      months. And 78.3% (72/92) patients continued to use pessary with the wearing time
      ranged 3 - 69 months; 21.7% (20/92) patients discontinued with the wearing time
      ranged 1 - 38 month, 14 patients (14/20) gave up in the initial 6 months. The
      median scores of PFDI-20 and PFIQ-7 questionnaires before pessary use were 50.0
      and 47.6, which decreased to 8.9 and 0.0 after pessary use (P < 0.05). And 87.1%
      (61/70) patients were satisfied. There was no significantly difference among 3
      groups on clinical characteristics, such as age, body mass index (BMI), pelvic
      surgery and so on (P > 0.05). The main factor influencing satisfaction degree and
      causing discontinuation was difficulties in placing and removing. CONCLUSIONS:
      Silicone pessary is effective for patients with POP. It could relieve discomfort
      symptoms and improve quality of life. The main factor influencing pessary use is
      difficulties in placing and removing. Thus, More suggestions are needed for
      patients in the initial 6 months.

PMID- 23141157
TI  - [Study on ischiospinous ligament fixation in treatment of stage III pelvic organ
      prolapse].
AB  - OBJECTIVE: To evaluate the safety and efficacy of ischiospinous ligament fixation
      in treatment of stage III pelvic organ prolapse (POP). METHODS: Between March
      2007 and December 2009, 65 patients with stage III POP who underwent
      ischiospinous ligament fixation in Peking Union Medical College Hospital were
      enrolled in this study. Among 21 cases complicated with stress urinary
      incontinence (SUI) underwent transobturator tension-free vaginal tape (TVT-O)
      concomitantly. Clinical parameter associated with perioperation, objective and
      subjective successful rate and complication were recorded. RESULTS: The mean
      operating time was (71 +/- 22) min and the mean blood loss was (93 +/- 40) ml. No
      intraoperative blood transfusion and viscera injury cases were observed. All
      patients were able to recover spontaneous micturition. Two cases experienced
      pelvic hematoma with diameter of 7 cm, after conservative treatment, they all
      recovered later. The objective success rate was 100% at 6 weeks follow-up by POP
      Q scoring. And 46.2% (30/65) were followed up at range of 1 - 3 years, recurrence
      rate were 10% (3/30), and however, no operation were needed. At median of 20
      months, all patients were followed up by telephone, the subjective successful
      rate was 95.4% (62/65). At 6 weeks after operation, 6.2% (4/65) patients suffered
      from lower back pain and right thigh pain, visual analogue scale of pain was at
      range of 3 to 5, which relieved gradually after treatment and disappeared totally
      within 2 years. The rate of suture exposure was 10% (3/30), the new urinary
      incontinence 4.6% (3/65), and the new dyspareunia 12.5% (3/24). CONCLUSIONS:
      Ischiospinous ligament fixation is a safe and efficacious management.

PMID- 23141158
TI  - [Survey of long term female pelvic floor function and sexual life status after
      total hysterectomy].
AB  - OBJECTIVE: To evaluate status of female pelvic floor function and sexual life
      after total hysterectomy. METHODS: From March 2001 to January 2004, 92 patients
      with undergoing hysterectomy due to benign gynecological diseases were enrolled
      in this study. They were followed up at outpatient department, including pelvic
      examination, filling in female sexual quality questionnaire, pelvic floor
      distress inventory short form 20 (PFDI-20), pelvic floor distress impact
      questionnaire short form 7 (PFIQ-7) and quality of sexual life of chinese women
      questionnaire. RESULTS: At 6 years after total hysterectomy, it was observed that
      7 cases (7/92, 7.6%) were pelvic organ prolapse and 62 cases (62/92, 67.4%) were
      urinary incontinence. A median score of PFDI-20 were 4.67. A median score of PFIQ
      7 were 0. Symptoms of pelvic floor dysfunction concentrated in lower urinary
      tract (58 cases with cough leak, 32 cases with spot urine leakage, 31 cases with
      frequent micturition, 24 cases with urgent urination)and bowel symptoms (26 cases
      with constipation, 24 cases with defecation urgency, 21 cases without fully
      drained stool). In the 68 patients filling in female sexual quality
      questionnaire, an average score were (127 +/- 20) points. Female sexual quality
      questionnaire score, sexual satisfaction, sexual communication and adjustment,
      sexual response and sexual body image were positively correlated with the
      patients' income (r = 0.432, P = 0.007; r = 0.356, P = 0.028; r = 0.475, P =
      0.003; r = 0.421, P = 0.009; r = 0.324, P = 0.047). CONCLUSIONS: Hysterectomy may
      have long-term effect on female pelvic floor function and sexual life. Quality of
      sexual life in those patients was positively correlated with income.

PMID- 23141159
TI  - [Transvaginal Prosima mesh and high uterosacral ligament suspension in the
      treatment of severe pelvic organ prolapsey].
AB  - OBJECTIVE: To study the efficacy of performing transvaginal Prosima mesh with
      high uterosacral ligament suspension (HUS) in treatment of severe pelvic organ
      prolapse (POP). METHODS: From July 2010 to February 2011, 70 patients with severe
      POP underwent transvaginal prosima mesh with HUS in First Affiliated Hospital,
      General Hospital of People's Liberation Army. Clinical parameters of
      perioperation were collected. After 1 month and 2 - 3 months, perineal two
      dimensional ultrasound examination was performed to measure mesh length in
      midsagittal plane. Validated prolapse quality of life questionnaires, pelvic
      floor distress inventsry short form 20 (PFDI-20) and pelvic floor impact
      questionnaire short form 7 (PFIQ-7) were used to evaluate the therapeutic effect.
      The mean results of pre-operative PFIQ-7 and PFDI-20 was 54 and 51, respectively.
      RESULTS: Median operation time was (195 +/- 47) min and median blood loss was
      (160 +/- 64) ml. All the patients were followed for a mean time of 13 months (2 -
      19 months). Seven cases were found with mesh exposure with less than 1 cm(2). The
      objective cure rate was 100%. The mean score of post-operative PFIQ-7 and PFDI-20
      were both 19, which were significantly lower than those of pre-operation (P <
      0.05). Anterior Prosima mesh was 3.5 cm at 1 month by ultrasound examination, and
      the second result of ultrasound scans was 2.8 cm at 2 - 3 month, which were both
      shortened 2.5 cm and 3.2 cm when compared with that of original size.
      CONCLUSIONS: Transvaginal Prosima mesh placement with HUS is a safe and efficient
      surgery with less complication. Although mesh became shorter after 2 - 3 month,
      it did not affect surgery efficacy.

PMID- 23141160
TI  - [Study on modified Prolift for pelvic floor reconstruction in the prevention of
      stress urinary incontinence].
AB  - OBJECTIVE: To evaluate the safety and efficacy of modified Prolift pelvic floor
      reconstruction with improving the placement of Prolift-A in treatment of severe
      pelvic floor dysfunction and stress urinary incontinence (SUI). METHODS: From
      July 2008 to September 2010, 170 cases with severe pelvic organ prolapse (POP)
      treated by modified Prolift pelvic floor reconstruction surgery in Fuzhou General
      Hospital were enrolled in this study. The Prolift-A was laid tension-free under
      the mid-urethra with the position of Prolift-A displaced from the neck of bladder
      to the mid-urethra. No concomitant tension-free urethra suspender via vagina was
      performed. Primary outcomes were assessed with POP quantitation (POP-Q) system to
      evaluate the postoperative anatomical replacement stage. Secondary outcome
      measure were: urogenital distress inventory 6 (UDI-6), the incontinence impact
      questionnaire 7 (IIQ-7) and the pelvic floor incontinence questionnaire 7 (PFIQ
      7) to evaluate the impact on life quality at the follow-up of 1, 6, 12 months.
      RESULTS: At 6 and 12 months after surgery, 168 cases and 163 cases were followed
      up. The anatomical cure rates were 98.8% (166/168) at 6 months and 97.5%
      (159/163) at 12 months, respectively. One case with bladder injury and 1 case
      with rectum injury were observed. Five cases with recurrence were observed,
      including 2 cases with anterior vagina prolapse, 2 cases with uterine prolapse
      and 1 case with posterior vagina prolapse. Meanwhile, 3 cases with hematoma and 7
      cases with mesh erosion were observed. Quality of life of all patients were
      improved significantly by UDI-6, IIQ-7 and PFIQ-7 scoring system evaluation.
      Among 79 POP patients with SUI, the cure rate of SUI was 93.7% (74/79). Of 5
      cases with symptomatic SUI, 2 cases were needed surgical intervention. Twenty
      three cases were found with minimal SUI symptoms and subjective satisfaction
      without objective influence on quality of life. Seven patients presented dysuria
      after surgery, 5 cases recovered urination with 10 days, 1 case recovered with 1
      months, and 1 case with 6 months by bladder drainage. Eleven cases with
      discomfort urination and 3 cases with slow urination were found. CONCLUSIONS: The
      modified Prolift pelvic reconstructive surgery was safe and efficacy intervention
      in treatment of POP and prevention of SUI.

PMID- 23141161
TI  - [Relationship of S100B protein expression and the pathogenesis of early-onset and
      late-onset preeclampsia].
AB  - OBJECTIVE: To investigate the relationship of S100B protein expression and the
      pathogenesis of early-onset and late-onset preeclampsia. METHODS: Sixty patients
      with preeclampsia who received caesarean section at Qingdao Municipal Hospital
      from October 2010 to September 2011 were enrolled in this study. Thirty cases
      were early-onset preeclampsia (referred as early-onset preeclampsia group, < 34
      weeks), and the other 30 cases were late-onset preeclampsia (referred as late
      onset preeclampsia group, >= 34 weeks). Thirty women who received caesarean
      section because of pelvic structural deformities, breech presentation, macrosomia
      and social factors were included as the control group. The expression of S100B
      mRNA in the placenta was detected by reverse transcription (RT)-PCR. The
      expression of S100B protein in the placenta was detected by immunohistochemistry.
      RESULTS: (1) S100B mRNA was expressed in the trophoblasts of preeclampsia and
      control groups. The expression of S100B mRNA in early-onset preeclampsia group
      (0.73 +/- 0.11) was significantly higher than the control group (0.58 +/- 0.08)
      and late-onset preeclampsia group (0.64 +/- 0.10, P < 0.05). There was no
      significant difference between late-onset preeclampsia group and the control
      group (P > 0.05). (2) S100B protein was expressed in the plasma membrane and
      cytoplasm of the trophoblasts, correlated positively with the brownish yellow and
      brown particles inside the cells. It was expressed in all the three groups.
      Immunohistochemistry revealed that the expression of S100B protein in the
      placenta of early-onset preeclampsia group was 100% (30/30), significantly higher
      than those of late-onset preeclampsia group and the control group, in which the
      positive rate were 70% (21/30) and 63% (19/30) respectively (P < 0.05). There was
      no difference between late-onset preeclampsia group and the control group (P >
      0.05). CONCLUSION: Early-onset and late-onset preeclampsia may have different
      etiology and pathogenesis. S100B may be a factor in the pathogenesis of early
      onset preeclampsia.

PMID- 23141162
TI  - [Distribution and normal reference range of fetal nuchal translucency thickness
      in Kunming pregnant women in the first trimester].
AB  - OBJECTIVE: To establish the normal reference range of fetal nuchal translucency
      (NT) thickness in Kunming Chinese pregnant women in the first trimester. METHODS:
      The study samples comprised of 1790 Kunming pregnant women who attended antenatal
      visit in the first trimester in the First Affiliated Hospital of Kunming Medical
      University. The general information including maternal date of birth, past
      pregnant history and other related conditions were recorded. The crown rump
      length (CRL) and NT thickness at 11 - 13(+6) gestational weeks were measured
      according to guidelines from Fetal Medicine Foundation (FMF). RESULTS: The total
      1790 of normal fetuses was recruited for final analysis. The mean and median
      values of CRL were (59.6 +/- 9.2) mm and 58.3 mm, respectively. The mean and
      median values of NT thickness were (1.7 +/- 0.5) mm and 1.7 mm, respectively.
      While the CRL were at between 45.0 - 54.9 mm, 55.0 - 64.9 mm, 65.0 - 74.9 mm and
      75.0 - 84.0 mm, the corresponding values of NT thickness were 1.0 mm, 1.3 mm, 1.5
      mm, 1.5 mm at the 5(th) percentile and 2.0 mm, 2.5 mm, 2.7 mm, 2.9 mm at the
      95(th) percentile, respectively, and the corresponding medial values of NT
      thickness were 1.4 mm, 1.7 mm, 2.0 mm, 2.0 mm, respectively. The NT thickness had
      no relationship with maternal age (P > 0.05). The mean value of NT thickness was
      (1.8 +/- 1.1) mm in male fetuses. The mean value of NT thickness was (1.7 +/-
      0.6) mm in female fetuses. The NT thickness in male fetuses was significantly
      thicker than that of females (P = 0.001). CONCLUSION: The present study
      established a reference range of normal fetal NT thickness corresponding with CRL
      in early pregnancy with reliable FMF quality control.

PMID- 23141163
TI  - [Clinical study on 48 cases with complete 17alpha-hydroxylase deficiency].
AB  - OBJECTIVE: To investigate efficient diagnosis and treatment of 17alpha
      hydroxylase (17OHD) deficiency by summarizing clinical characteristics of those
      patients. METHODS: From January 1983 to January 2010, 48 cases with 17OHD in
      Peking Union Medical College Hospital were studied retrospectively. RESULTS:
      Among 48 patients with 17OHD, karyotype analysis showed, 12 cases with 46, XX and
      36 cases with 46, XY. The 46, XX karyotype and 46, XY karyotype with complete
      17OHD had typical clinical presentation of amenorrhea[12/12, 100% (36/36)], no
      typical spontaneous puberty [12/12, 13.9% (5/36)], Hypertension [11/12, 100%
      (36/36)], hypokalemia [K(+): (2.6 +/- 0.7), (2.8 +/- 0.7) mmol/L],
      hypergonadotropin [follicle-stimulatinghormone (FSH): (51 +/- 35), (79 +/- 46)
      U/L, luteinizing hormone (LH): (27 +/- 14), (49 +/- 37) U/L], impaired production
      of sex hormones [testosterone (T): 0.003, 0.005 nmol/L; estradiol (E(2)): 26.86,
      10.64 pmol/L], hyper-progesterone[ (P): (32 +/- 15), (29 +/- 23) nmol/L],
      impaired production of 17alpha-hydroxyprogesterone (17alpha-OHP)[(2.5 +/- 1.1),
      (2.4 +/- 1.7) nmol/L], ACTH hypersecreation (91.8, 114.0 pmol/L). ACTH
      stimulating test did not elevated in 17alpha-OHP and cortisol. CONCLUSION: When
      patients with elevated basal serum levels of progesterone higher than that of
      ovulation period in addition to clinical symptoms, examination about 17OHD should
      be warranted.

PMID- 23141164
TI  - [Relationship of polymorphisms of AhR -1661G/A with GSTP1 -313A/G and
      susceptibility to endometriosis].
AB  - OBJECTIVE: To investigate the association of polymorphisms of arylhydrocarbon
      receptor (AhR)-1661G/A with glutathione S-transferase pi (GSTP1) -313A/G and the
      susceptibility to endometriosis in southern Han Chinese. METHODS: Total of 432
      endometriosis patients undergoing laparoscopic or laparotomy surgery matched with
      493 patients with fallopian tube ligation, tubal recanalization, laparoscopic
      hydrotubation, benign ovarian tumor and teratoma surgeries without endometriosis
      as control group were enrolled in this study. The single nucleotide polymorphism
      (SNP) of AhR -1661G/A and GSTP1 -313A/G were detected by using a fluorescent
      quantitative PCR-based high resolution melting (HRM). RESULTS: The numbers of
      combined genotypes AhR -1661G/A and GSTP1 -313A/G were 120 patients with AG + AA,
      64 patients with AG + AG, 8 patients with AG + GG, 109 patients with GG + AA, 84
      patients with GG + AG, 4 patients with GG + GG, 31 patients with AA + AA, 10
      patients with AA + AG, 1 patient with AA + GG at endometriosis group and 131
      patients with AG + AA, 68 patients with AG + AG, 6 patients with AG + GG, 157
      patients with GG + AA, 66 patients with GG + AG, 4 patients with GG + GG, 35
      patients with AA + AA, 20 patients with AA + AG, 3 patients with AA + GG at
      endometriosis group. There was no statistically different frequencies of
      genotypes between endometriosis group and control group (chi(2) = 12.558, P =
      0.128). Compared with genotype GG + AA, the risk of endometriosis with genotype
      GG + AG was increased 1.833 time (95%CI: 1.233 - 2.274). CONCLUSION: The combined
      genotype GG + AG [from AhR -1661G/A (GG) and GSTP1 -313A/G (AG)] might be related
      with susceptibility to endometriosis.

PMID- 23141165
TI  - [Study of the invasiveness and tumour formation of Bcrp1(+) HeLa cervical cancer
      cells].
AB  - OBJECTIVE: To make sure whether or not Bcrp1 is the marker of cervical cancer
      stem cells or not by studying the invasive ability and formation of tumors of
      Bcrp1(+) phenotype HeLa cells. METHODS: The tumor cell migration and invasion
      assay were used by boyden chamber to identify the invasive ability of Bcrp1(+)
      phenotype HeLa cells. The formation of tumors in vivo experiments were completed,
      in which the two groups of cells with different concentrations were inoculated in
      non obese diabetes-severe combined immunodeficiency disease (NOD/SCID) mice
      (1*10(4), 1*10(5), 1*10(6)/ml), and the differences of time, rate and volume in
      the formation of tumors between two groups were observed. RESULTS: (1) In the
      invasion assay, the amount of cells that invaded through the artificial basement
      membrane in Bcrp1(+) group were 99 +/- 14, which was significantly greater than
      those in Bcrp1(-) group (57 +/- 13, P < 0.05);the length of the Bcrp1(+) group
      was (366 +/- 52) um, which was significantly greater than the Bcrp1(-) group (301
      +/- 54) um (P < 0.05). (2) Following transplantation of 1*10(4) cells, only the
      Bcrp1(+) cells formed tumors in NOD/SCID mice. When 1*10(5) or 1*10(6) cells were
      transplanted, the tumor incidence and the tumor mass were greater in the Bcrp1(+)
      groups than those in the Bcrp1(-) groups (P < 0.05). CONCLUSION: Bcrp1(+) HeLa
      cell have the greater capacity of invasive and the tumorigenicity, which may
      contain cancer stem cells.

PMID- 23141166
TI  - Glatiramer acetate biases dendritic cells towards an anti-inflammatory phenotype
      by modulating OPN, IL-17, and RORgammat responses and by increasing IL-10
      production in experimental allergic encephalomyelitis.
AB  - Paralleling our previous mechanistic studies of glatiramer acetate (GA; Copaxone)
      activity, we show that GA curbs the expression of Toll-like receptor (TLR) 9 and
      the universal adapter protein Myd88 in mice with EAE, the animal model for
      multiple sclerosis. Concurrent with enhanced dendritic cell (DC) production of IL
      10, GA interferes with OPN, IL-17, and ROR gamma expression in DCs of mice with
      EAE, and suppresses brain expression of the EAE-induced chemokines, MIP1alpha and
      beta, IP-10 and RANTES. Thus GA not only biases dendritic cells towards an anti
      inflammatory phenotype, but also suppresses the expression of factors that affect
      the blood-brain barrier penetration during neuroinflammation.

PMID- 23141167
TI  - [Retrobulbar optic neuropathy secondary to an undifferentiated carcinoma of the
      sphenoid sinus].
AB  - Undifferentiated carcinoma of the paranasal sinuses is a rare malignant tumor,
      characterized by rapid growth, local/regional invasion, metastatic potential and
      poor prognosis despite aggressive treatment. Clinically, this tumor may manifest
      as episodes of epistaxis, headache or ophthalmic signs, particularly oculomotor
      nerve palsies, optic atrophy or even proptosis in the case of orbital extension.
      We report the case of a patient admitted with a left retrobulbar optic
      neuropathy, which led to a diagnosis of undifferentiated carcinoma of the
      sphenoid sinus.

PMID- 23141168
TI  - HPLC-UV-ESI-MS analysis of phenolic compounds and antioxidant properties of
      Hypericum undulatum shoot cultures and wild-growing plants.
AB  - LC-UV and LC-MS analysis were used to study the phenolic composition of water
      extracts of Hypericum undulatum (HU) shoot cultures and wild-growing (WG) plants.
      Total phenolic content (TPC), determined using the Folin-Ciocalteu assay, and the
      antioxidant activity measured by two complementary methods were also performed
      for each sample. Mass spectrometry revealed several phenolics acids with quinic
      acid moieties, flavonols, mostly quercetin, luteolin and apigenin glycosides,
      flavan-3-ols (catechin and epicatechin) and the xanthonoid mangiferin.
      Differences in phenolic composition profile and TPC were found between the
      samples. The major phenolic in HU culture-growing (CG) samples is chlorogenic
      acid, followed by epicatechin, quercitrin and isoquercitrin. The WG plants
      presents hyperoside as the main phenolic, followed by isoquercitrin, chlorogenic
      acid and quercetin. The TPC and antioxidant activity were higher in samples from
      WG plants.

PMID- 23141169
TI  - Interleukin-1beta, tumour necrosis factor-alpha and lipopolysaccharide induce C
      type natriuretic peptide from canine aortic endothelial cells.
AB  - The N-terminal portion of pro C-type natriuretic peptide (NT-pCNP) has shown
      promise as a biomarker for sepsis in humans and dogs, however the mechanism of NT
      pCNP production in dogs is unknown. Canine aortic endothelial cells were
      stimulated with lipopolysaccharide, lipoteichoic acid, peptidoglycan, TNF-alpha,
      IL-1beta, IL-6, IL-10, IL-21, CXCL-8, IFN-gamma, VEGF-A or control (PBS), and NT
      pCNP production was measured. Lipopolysaccharide, TNF-alpha, and IL-1beta
      significantly stimulated NT-pCNP production in a dose and time dependent manner;
      IL-1beta resulted in the greatest NT-pCNP concentrations. The other stimulants
      did not result in significant NT-pCNP production. The addition of serum to the
      cell culture model did not alter lipopolysaccharide, lipoteichoic acid or
      peptidoglycan induced NT-pCNP production. These data indicate that
      lipopolysaccharide, TNF-alpha and IL-1beta regulate CNP production from canine
      vascular endothelium and of the stimulants tested, IL-1beta is the predominant
      inducing factor. These data provide some initial insight into the mechanisms of
      CNP regulation in dogs.

PMID- 23141170
TI  - Verification of natural infection of peridomestic rodents by PCV2 on commercial
      swine farms.
AB  - The porcine circovirus-2 (PCV2) is the main agent responsible for porcine
      circovirus associated diseases (PCVAD). Few studies have been done regarding PCV2
      infection in other species. The purpose of this study was to investigate the
      occurrence of PCV2 infection in the peridomestic rodent species Mus musculus and
      Rattus rattus on commercial pig farms in Brazil. Immunohistochemistry assay
      demonstrated PCV2 in the spleen, lung and kidney. Viral DNA was detected in
      tissues by nested PCR assay. Partial sequences of PCV2 genomes detected in the
      rodents had strong identity with gene sequences of PCV2 isolates from pigs. These
      results show that the studied peridomestic rodent species can be naturally
      infected by PCV2. However, further studies are needed to confirm PCV2
      transmission from rodents to pigs.

PMID- 23141171
TI  - The influence of enclosure design on diurnal activity and stereotypic behaviour
      in captive Malayan Sun bears (Helarctos malayanus).
AB  - The effect of enclosure design on diurnal activity and stereotypic behaviour was
      assessed in 17 adult Malayan Sun bears (Helarctos malayanus), kept either in
      barren indoor enclosures or relatively enriched outdoor enclosures. Locomotion
      was the most frequent activity observed in the indoor bears, followed by resting.
      In contrast, conspecifics housed outdoors spent most of the time resting. Eleven
      forms of stereotypic behaviours were recorded in the bears, with pacing being the
      most common. The frequency and repertoire of stereotypies were significantly
      higher in the indoor bears irrespective of enclosure size. Novel forms of
      locomotor (forward-reverse pacing) and oral (allo-sucking) stereotypies were
      recorded. Oral stereotypies were predominant in the bears housed indoors, while
      patrolling was confined to the outdoor bears. Enclosure complexity significantly
      influences activity budget and occurrence of stereotypic behaviours, highlighting
      the importance of appropriate enclosure design and enrichment for the welfare of
      captive bears.

PMID- 23141172
TI  - [Key problems of chemotherapy for gynecological malignancies].

PMID- 23141173
TI  - [Synopsis of the third national seminar on chemotherapy for gynecological
      malignancies].

PMID- 23141174
TI  - [Value of CA(125) in the prediction of optimal interval debulking surgery and its
      prognosis in patients with epithelial ovarian cancer].
AB  - OBJECTIVE: To investigate the changes of CA(125) between primary cytoreductive
      surgery and interval debulking surgery for prediction the rate of optimal
      interval cytoreductive surgery and prediction the recurrence and the prognosis in
      patients with epithelial ovarian cancer. METHODS: A total of 39 cases with
      suboptimal primary cytoreductive surgery admitted from Jan. 1996 to Jan. 2009
      were retrospectively analyzed. The median age of patients was 56 years (range: 41
      - 68 years). Based on the changes in CA(125) level between primary cytoreductive
      surgery and interval debulking surgery, all cases were divided into four groups,
      group A (CA(125) reduced to normal after primary cytoreductive surgery, n = 6),
      group B (CA(125) reduced to normal after 1-2 cycles of chemotherapy, n = 11),
      group C (CA(125) reduced to normal after 3-4 cycles of chemotherapy, n = 14), and
      group D (CA(125) did not reduced to normal after the chemotherapy, n = 8), and
      all received platinum-based chemotherapy. The response to chemotherapy evaluated
      by pathological examination versus CA(125) level, and recurrence and prognoses
      were also analyzed. RESULTS: (1) The rate of optimal interval cytoreductive
      surgery in group A, B, C and D were 6/6, 8/11, 9/14 and 2/8 respectively, in
      which there were statistically different between group A or B and group D (P <
      0.05). (2) The clinical benefit rates evaluated by the pathological examination
      in group A, B, C and D were 4/6, 4/11, 5/14 and 0, respectively and there were
      statistically different between group A and group D (P = 0.030). (3) There was
      significant difference in the recurrence rate between group A and group D (3/6
      vs. 8/8, P = 0.024), while there were not significant differences between group B
      or C and group D (all P > 0.05). The rate of drug-resistant recurrence in group
      A, B, C and D were 1/6, 3/11, 5/14 and 7/8, respectively, in which there were
      significant differences between group A, B or C and group D (all P < 0.05). (4)
      The median progression-free survival (PFS) for patients in group A, B, C and D
      were 32, 10, 18 and 3 months, respectively, in which there were significant
      differences in the PFS between group A, B or C and group D (P = 0.012, P = 0.003,
      P = 0.032). The median overall survival (OS) were 44, 45, 44 and 16 months,
      respectively. There were significant differences in the OS between group A, B or
      C and group D (P = 0.022, P = 0.004, P = 0.000). CONCLUSION: The change of
      CA(125) between primary cytoreductive surgery and interval debulking surgery may
      be predict the recurrence type and the prognosis in patients with epithelial
      ovarian cancer.

PMID- 23141175
TI  - [Therapeutic evaluation of cisplatin, etoposide, and bleomycin chemotherapy
      regimen in high-risk gestational trophoblastic neoplasia].
AB  - OBJECTIVE: To evaluate the effectiveness and safety of combination chemotherapy
      with bleomycin, etoposide and cisplatin (BEP) regimen on the patients with high
      risk gestational trophoblastic neoplasia (GTN). METHODS: Forty-two patients with
      high-risk GTN admitted in Sichuan Cancer Hospital between Jan.1997 and Oct. 2011
      were analyzed retrospectively. The International Federation of Gynecology and
      Obstetrics (FIGO) prognostic score of all patients was more than 7. The mean age
      of patients was 30.2 years (range 20 - 49 years). All patients were treated with
      more than two cycles BEP regimen and followed up to the patients' death or at the
      end of Feb.2012. The clinical response, toxicity and the occurrence of secondary
      tumors were investigated. RESULTS: Forty-two high-risk GTN patients received the
      total of 251 courses of the BEP regimen, the average number of courses for each
      patient was 6.0 courses. Thirty-seven patients achieved complete remission and 5
      patients showed drug-resistant. The total complete remission rate of BEP regimen
      was 88% (37/42). Among the complete remission patients, the total courses of BEP
      regimen of cases getting normal serum beta-hCG level was 129 courses (average 3.5
      courses), and the total courses of cases achieving complete remission was 227
      courses (average 6.1 courses). Among the 37 complete remission patients, 31 cases
      were treated with BEP regimen chemotherapy alone, 4 patients with BEP regimen
      chemotherapy combined with surgical treatment (1 case had no cancer after
      surgery) and 2 cases with BEP regimen chemotherapy combined with radiation
      therapy. Therefore, the complete remission rate of BEP regimen chemotherapy alone
      was 74% (31/42). There were 5 patients who showed drug-resistance after 24
      courses of BEP regimen chemotherapy (average 4.8 courses), then received
      etoposide, methotrexate and dactinomycin (EMA)/cyclophosphamide and vincristine
      sulfate (CO) regimen chemotherapy after drug-resistance, 2 cases combined with
      radiation therapy, 1 case combined with surgical treatment. Ultimately, 4 cases
      achieved complete remission, 1 case died of cancer. The major toxicities of BEP
      regimen were included bone marrow suppression, digestive tract side effect and
      alopecic, followed by mild peripheral neuritis and abnormal liver function, rare
      cases of mild pulmonary toxicity. There were no severe anaphylaxis and obvious
      impairment of cardiac, liver, pulmonary and kidney function, except 1 patient (49
      years old) had grade IV bone marrow suppression and pulmonary fibrosis worsened
      after chemotherapy. The bone marrow suppression was mainly I-III degree
      neutropenia, and Incidence rate was 66.5% (167/251). All the survival patients
      without secondary tumor. CONCLUSION: For young high-risk GTN patients, BEP
      regimen chemotherapy may be safe and effective.

PMID- 23141176
TI  - [Effects of pre-chemotherapy hemoglobin and platelet levels in patients with
      stage Ib2-IIb cervical cancer treated with neoadjuvant chemotherapy followed by
      radical hysterectomy].
AB  - OBJECTIVE: To investigate the role of pre-chemotherapy hemoglobin and platelet
      levels in the effect of chemotherapy and prognostic outcome in patients with
      International Federation of Gynecology and Obstetrics (FIGO) stage Ib2-IIb
      cervical cancer treated with neoadjuvant chemotherapy followed by radical
      hysterectomy. METHODS: From January 1999 to December 2010, 111 patients with FIGO
      stage Ib2-IIb who underwent chemosurgical treatment at the department of
      obstetrics and gynecology in Peking Union Medical College Hospital were reviewed.
      The median age of patients was 42 years (range: 21 - 68 years). The median level
      of prechemotherapy hemoglobin and platelet levels was 127 g/L and 266 * 10(9)/L,
      respectively. Chemotherapy response was evaluated according to the WHO criteria,
      including complete response (CR), partial response (PR), stable disease (SD) and
      progressive disease (PD). Patients who achieved CR or PR were defined as
      responder. Rates of clinical response were compared with the clinical
      pathological variables using chi-square test. Multiple logistic regression was
      carried out to evaluate the relationship among the probability of achieving an
      optimal clinical response and the variables. The log-rank test was used to
      compare the homogeneity of progression-free survival and overall survival
      functions across strata defined by categories of prognostic variables. The Cox
      proportional hazard model was used to assess the significance of potential
      prognostic factors for progression-free survival and overall survival. RESULTS:
      All patients received one to three cycles of chemotherapy. After the neoadjuvant
      chemotherapy, 9 patients achieved CR, 77 patients PR, 23 patients SD, 2 patients
      PD. The overall response rate was 77.5% (86/111). By univariate analysis, the
      clinical response rate was associated with tumor grade (P = 0.026), deep cervical
      stromal invasion (P = 0.029) and positive lymph nodes (P = 0.048). By multiple
      logistic regression, deep cervical stromal invasion (P = 0.015) and positive
      lymph nodes (P = 0.031) were independent predictors of optimal clinical response.
      By log-rank test, 5-year overall survival rate and 5-year progression-free
      survival rate were associated with lymph nodes metastases status and
      lymphovascular invasion (P = 0.000), but not with hemoglobin and platelet levels
      (P > 0.05). By Cox regression model, lymph nodes metastases status and lymph
      vascular space involvement (P < 0.01) were independently prognostic factors of 5
      year overall survival rate and 5-year progression-free survival rate. CONCLUSION:
      Pretreatment hemoglobin and platelet levels were neither predictors of clinical
      response to chemotherapy nor prognostic factors.

PMID- 23141177
TI  - [Effect of evidence-based medicine on the decision of chemotherapy for epithelial
      ovarian cancer].

PMID- 23141178
TI  - [Fetoscopic guided laser occlusion for twin-to-twin transfusion syndrome in 33
      cases].
AB  - OBJECTIVE: To evaluate the clinical effect of fetoscopic laser occlusion of
      chorioangiopagous vessels (FLOC) for monochorionic diamniotic twins (MCDA)
      pregnancies complicated with twin-to-twin transfusion syndrome(TTTS). METHODS:
      The clinical data of 33 consecutive cases of TTTS from Mainland China, who had
      FLOC in the Department of Obstetrics and Gynaecology of Prince of Wales Hospital
      (The Chinese University of Hong Kong) from November 2003 to December 2010, were
      reviewed and analyzed for peri-operative complications, perinatal outcomes and
      fetal survival rate. Clinical stage of TTTS was according to the Quintero staging
      system. RESULTS: (1) Pregnancy characteristics: the mean maternal age was 30; the
      median gestational age at FLOC was 23(+4) weeks; according to the Quintero
      staging system, 3 cases were Quintero staging I, 14 cases were Quintero staging
      II, 7 cases were Quintero staging III and 9 cases were Quintero staging IV. For
      the 3 stage I cases, FLOC was performed for severe maternal symptoms of
      polyhyramnios or severe fetal cardiac dysfunction. (2) COMPLICATIONS:
      intraoperative complications occurred in 5 patients including four uterine
      bleedings at the puncture site, one placental vascular anastomosis bleeding.
      Postoperative complications occurred in 6 patients including 2 abortions and 1
      intrauterine death within one week after operation, 2 abortions and 1 amniotic
      band syndrome occurred from two to four weeks after operation. (3) Perinatal
      outcome and fetal survival rate: the median interval of 33 patients between FLOC
      and delivery was 9(+4) weeks; the median gestational age at delivery was 31(+6)
      weeks; the gestation at delivery was less than 24 weeks in 6% (2/33), 24 to 28
      weeks in 21% (7/33), 28 to 32 weeks in 18% (6/33), 32 to 37 weeks in 55% (18/33).
      The mean birth weight of the donor was 1600 g (350 - 2520 g); the mean birth
      weight of the recipiert was 1930 g (400 - 3040 g). The overall survival rate, the
      double infant survival rate, the single survival rate and survival rate for at
      least one twin was 59% (39/66), 52% (17/33), 15% (5/33) and 67% (22/33),
      respectively. The overall survival rate dropped from 61% (17/28) in Quintero
      staging II to 9/18 in Quintero staging IV. CONCLUSIONS: FLOC for MCDA complicated
      with TTTS is associated with an overall survival of about 60%. Major
      complications are rare. The outcome is not only related to Quintero staging but
      also the close monitoring and timely termination of pregnancy.

PMID- 23141179
TI  - [Clinical efficacy and perinatal outcome of nifedipine for severe preeclampsia:
      meta-analysis].
AB  - OBJECTIVE: To assess the efficacy, side effects and perinatal outcome of
      nifedipine compared with other antihypertensives for treating severe preeclampsia
      in pregnant women. METHODS: Randomized controlled trials (RCTs) that comparing
      nifedipine with other antihypertensives for severe preeclampsia were searched in
      PubMed, EMBase, Cochrane library, CNKI and VIP database etc(till January 2012).
      The quality of the included RCTs was evaluated, and Meta-analysis was performed
      with Rev Man 5.1 software. RESULTS: Nine trials were included, involving 386
      women in the nifedipine group, and 378 women in other antihypertensives group.
      Compared with other antihypertensives, nifidepine was associated with greater
      effective control of blood pressure (OR = 2.65, 95%CI: 1.65 - 4.25, P < 0.01).
      There was no clear difference in the time needed to control blood pressure (WMD =
      -3.64, 95%CI: -10.90 - 3.61, P = 0.32). Nifedipine could prolong gestation better
      than other antihypertensives (WMD = 5.14, 95%CI: 3.29 - 6.99, P < 0.01). There
      were no clear differences in maternal side effects headache (P = 0.28),
      palpitation (P = 0.06), and nausea vomiting (P = 0.28). No noticeable difference
      was found between the two groups in the Apgar score at five minutes (WMD = -0.21,
      95%CI: -0.32 - 0.91, P = 0.72), neonatal respiratory distress syndrome (OR =
      1.24, 95%CI: 0.57 - 2.67, P = 0.59), or perinatal deaths (OR = 0.49, 95%CI: 0.22 
      1.11, P = 0.09). CONCLUSION: Nifedipine is associated with greater effective
      control of blood pressure and prolongation of gestation, with no additional
      neonatal respiratory distress syndrome or perinatal deaths, compared with other
      antihypertensives for women with severe preeclampsia.

PMID- 23141180
TI  - [Clinical study on cervical intraepithelial neoplasia with high-risk HPV
      infection among pregnant women].
AB  - OBJECTIVE: To investigate the relationship between cervical intraepithelial
      neoplasia (CIN) and high-risk (HR) HPV infection among late pregnant women.
      METHODS: From Aug. 2007 to Feb. 2010, 168 women at 13 to 32 gestational weeks
      undergoing prenatal examination in Beijing Obstetrics and Gynecology Hospital
      went through three stage cervical disease screening, including 21 women with
      cervicitis and 147 women with CIN (42 women with CIN III, 37 women with CIN II
      and 68 women with CIN I). Hybrid capture assay version II (HC-II) test was used
      to measure HR-HPV DNA load, and the logarithmic transtormation (log(10)) was
      performed. All 168 women were followed up to postpartum 3 - 6 months. HR-HPV
      infections rates of cervicitis and different CIN, the rate of HR-HPV infection
      turned naturally negative at postpartum of 3 to 6 months, and HR-HPV load at
      pregnancy and 3 - 6 months postpartum were observed. RESULTS: (1) HR-HPV
      infection rate: CIN III, II, I and cervicitis pregnant women's HR-HPV positive
      infection rates were 98% (41/42), 86% (32/37), 76% (52/68) and 62% (13/21)
      respectively, which reached statistical difference (P = 0.002). (2) HR-HPV
      naturally negative: the rate of pregnant women with different levels of CIN who
      turned HR-HPV naturally negative within 3 - 6 months of postpartum were CIN III
      5% (2/41), CINII 47% (15/32), CINI52% (27/52) and cervicitis 10/13, which also
      reached statistical difference among those four groups (P = 0.000). (3) HR-HPV
      load: pregnant women with different grade of CIN and cervicitis HR-HPV DNA load
      were CIN III 2.02 ng/L(1.53, 2.67 ng/L), CINII 1.94 ng/L (0.75, 2.75 ng/L),
      CINI2.04 ng/L (0.08, 2.95 ng/L) and cervicitis 1.98 ng/L (-0.07, 2.47 ng/L).
      There was no significantly different HPV load in women with cervicitis and
      different CIN (P = 0.719). At 3 - 6 months postpartum, HR-HPV load was CIN III
      1.55 ng/L (0.90, 2.10 ng/L), which was significantly higher than the amount of
      CINII 0.09 ng/L (-0.69, 1.74 ng/L), CINI0.48 ng/L (-0.56, 2.2 ng/L) and
      cervicitis -0.46 ng/L (-0.78, 1.40 ng/L, P = 0.036). CONCLUSIONS: With the
      increasing of CIN grade, the rate of HR-HPV infection in pregnant women was
      increased, however, the rate of HR-HPV turning negative naturally at 3 - 6 months
      postpartum decreased. With different CIN grade during pregnancy, HR-HPV DNA load
      did not change significantly, but HR-HPV DNA load increased at 3 - 6 months of
      postpartum. HR-HPV DNA loads with the same grade of CIN and cervicitis during
      pregnancy higher than that of postpartum among pregnant women.

PMID- 23141181
TI  - [Efficacy of conservative laparoscopic surgery combined with goserelin in
      treatment of 206 patients with severe ovarian endometriosis at short-term and
      long-term follow-up].
AB  - OBJECTIVE: To evaluate the short-term and long-term efficacy of conservative
      laparoscopic surgery combine with goserelin in treatment of severe ovarian
      endometriosis. METHODS: From January 2004 to December 2008, 206 patients with
      severe ovarian endometriosis underwent laparoscopy surgery in Nanjing Drum Tower
      Hospital, Affiliated Nanjing University Medical School were enrolled in this
      retrospective study. According to the revised classification American Fertility
      Society (r-AFS), 123 (123/206, 59.7%) cases were at stage III and 83 (83/206,
      40.3%) patients were at stage IV. Among 138 cases presented pelvic pain. All the
      patients underwent laparoscopic cystectomy, of which 117 patients with
      childbearing preserving underwent hysteroscopy and hydrotubation examination,
      including 7 cases with bilateral salpingectomy, 2 cases with bilateral tubal
      obstruction and 108 cases with normal reproduction. After surgery, all cases were
      administered by goserelin treatment at dose of 3.6 mg per 28 days for 3 to 6
      months. At 1 to 5 years following up, pelvic pain, pregnancy and recurrence were
      observed, those factors associated with pregnancy rate and endometriosis
      recurrence were analyzed. RESULTS: (1) Pelvic pain: complete remission rate of
      pelvic pain was 76.1% (105/138) at 1 to 5 years after surgery. (2) Pregnancy:
      total pregnancy rate was 70.4% (76/108), spontaneous pregnancy rate was 68.8%
      (66/96) and pregnant rate of in vitro fertilization and embryo transfer (IVF-ET)
      was 10/12. Pregnancy rate at 1 year was 57.3% (55/96) and accounting for 83.3%
      (55/66) in all pregnant women. Live birth rates of spontaneous pregnant and IVF
      ET were 86.4% (57/66) and 9/10, respectively. (3) Recurrence: the total
      recurrence rate was 8.3% (17/206) at 1 to 5 years. The recurrence rates and the
      cumulative recurrence rates were 3.9% (8/206) and 3.9% (8/206) at the first year
      after operation, 2.0% (3/149) and 6.7% (10/149) at the second year, 1.0% (1/99)
      and 8.0% (8/99) at the third year, 10.9% (5/46) and 17.4% (8/46) at the fourth
      year, 0 and 2/18 at the fifth year, respectively. CONCLUSION: It was suggested
      that conservative laparoscopic surgery combined with goserelin in treatment of
      stage III or IV ovarian endometriosis could reduce the recurrence risk of severe
      ovarian endometriosis and improve the pregnant rate of endometriosis-associated
      infertility.

PMID- 23141182
TI  - [Impact of vaginal mesh exposure on quality of life in patients undergoing
      transvaginal reconstructive pelvic surgery with polypropylene mesh].
AB  - OBJECTIVE: To study the impact of vaginal mesh exposure on quality of life in
      patients undergoing transvaginal reconstructive pelvic surgery (RPS) with
      polypropylene mesh. METHODS: From May 2004 to March 2011, 114 patients with
      severe pelvic organ prolapse (POP) undergoing transvaginal RPS with polypropylene
      mesh were enrolled in this study, which were divided into exposure and non
      exposure group according to appearing vaginal mesh exposure at 2 months, 6 months
      and 1 year after operation. At the same time, pelvic floor distress inventory
      short form 20 (PFDI-20) and pelvic floor impact questionnaire short form 7 (PFIQ
      7) were completed in those patients. RESULTS: At 2 months after operation, 96
      patients were followed up, including 19 patients in exposure group and 77
      patients in non-exposure group, and the rate of exposure was 19.8% (19/96); At 6
      months after operation, 85 patients were followed up, including 13 patients in
      exposure group and 72 patients in non-exposure group, and the rate of exposure
      was 15.3% (13/85); At 1 year after operation, 77 patients were followed up,
      including 6 patients in exposure group and 71 patients in non-exposure group, and
      the rate of exposure was 7.8% (6/77). Mean score of PFDI-20 and PFIQ-7 in
      exposure group before operation was 39.6 and 57.1, which was statistically
      improved to 8.3 and 9.5 at 2 months after operation, 8.3 and 9.5 at 6 months
      after operation, 2.1 and 0 in 1 year after operation (P < 0.01). Mean score of
      PFDI-20 and PFIQ-7 of non-exposure group before operation was 54.2 and 66.7,
      which was improved to 8.3 and 4.8 at 2 months after operation, 0 at 6 months and
      1 year after operation, but there was no significant difference in mean score of
      PFDI-20 and PFIQ-7 between the two groups (P > 0.05). CONCLUSION: Vaginal mesh
      exposure was common after transvaginal RPS with polypropylene mesh, however, most
      of them were moderate, and there was no significant impact on patients' qualifies
      of life.

PMID- 23141183
TI  - [Ovarian torsion after controlled ovarian hyperstimulation: 5 cases report and
      clinical analysis].
AB  - OBJECTIVE: To evaluate the characteristics and treatment of ovary torsion after
      controlled ovarian hyperstimulation. METHODS: Between Jan.2008 and Dec.2011, 5
      cases with ovary torsion who underwent ovarian hyperstimulation were
      retrospectively studied. RESULTS: Five cases presented intermittent lower
      abdominal from 1 to 38 days after oocyte retrieval. Enlargement of ovary and
      decreased or absent venous and/or arterial flow were demonstrated by Doppler
      sonography. Two torsions at left side, two torsions at right side, and one on
      bilateral side were observed. Three cases give up embryo transplantation, 2 cases
      were pregnant after surgical treatment. One case with partial torsion was
      successfully treated with simple conservative treatment. Two cases with complete
      torsion were performed adnexectomy by laparotomy. One case with complete torsion
      with early pregnancy was managed by laparoscopic adnexectomy. One case with
      chemical pregnancy was managed by laparoscopic detorsion for left side and
      excision for right side. Postoperative pathology of ovary tissue all confirmed
      haemorrhage and necrosis. CONCLUSIONS: Ovary torsion might occur after controlled
      ovarian hyperstimulation. The early management on ovary torsion will be benefit
      for preserving ovarian function.

PMID- 23141184
TI  - [Cyr61 expression influences cancer cell proliferation and apoptosis via PI3K
      pathway in human ovarian carcinoma cells].
AB  - OBJECTIVE: To investigate the relationship between cysteine-rich protein 61
      (Cyr61) and phosphatidylinositol 3-kinase (PI3K) signal pathway on cell
      proliferation and apoptotic in human ovarian carcinoma cells. METHODS:
      Recombinant human Cyr61 (rhCyr61) was pretreated with ovarian carcinoma cells.
      The expression of Cyr61 protein was detected by confocal spectral microscopy.
      Then treated the ovarian carcinoma cells with PI3K transduction inhibitors
      (LY294002) for 24 hours. Cell apoptosis was detected by flow cytometry (FCM).
      Cell viability was determined by methyl thiazolyl tetrazolium (MTT) method. The
      mRNA expressions of Cyr61, the protein levels of protein kinase B (PKB), phospho
      PKB and Cyr61 were assayed by real time-PCR and western blot analysis,
      respectively. RESULTS: The Cyr61 and phospho-PKB protein expression in two
      ovarian carcinoma cells (OV2008 and OVCAR-3) were increased in rhCyr61 pretreated
      group. The decreasing of cell apoptosis [(1.4 +/- 0.9)%, (2.1 +/- 1.0)%] and
      increasing of cell proliferation [(124.0 +/- 1.8)%, (133.0 +/- 2.2)%] was
      detected in the same time, compared with negative control group, there were
      significant difference (P < 0.05). After exposed to LY294002 for 24 hours, the
      apoptosis rate of OV2008 and OVCAR-3 in pretreated with rhCyr61 group exposed to
      LY294002 were (21.1 +/- 1.6)% and (26.4 +/- 1.5)%, respectively. Cells viability
      [(59.0 +/- 2.3)%, (51.0 +/- 2.0)%] was also significantly decreased in OV2008 and
      OVCAR-3 pretreated with rhCyr61 cells. Meanwhile, the mRNA expressions of Cyr61
      (3.2 +/- 0.8, 6.2 +/- 1.1) and the protein levels of phospho-PKB and Cyr61 were
      greatly decreased. Compared with negative control group, there were significant
      difference in OV2008 and OVCAR-3 cells (all P < 0.01). CONCLUSIONS: The
      activation of PI3K intracellular signaling pathways may lead to up-regulation of
      Cyr61 expression. Block PI3K signal pathway could significantly inhibit the
      expression of Cyr61, and may promote the apoptotic effects and inhibit the cell
      growth of ovarian carcinoma cells.

PMID- 23141185
TI  - Activation of acetylcholine receptors and microglia in hypoxic-ischemic brain
      damage in newborn rats.
AB  - OBJECTIVE: We previously showed that acetylcholine receptor (AChR) agonist
      reduced hypoxic-ischemic brain damage in the newborn rats. To further
      investigated the interaction between hypoxia and chorinergic anti-inflammatory
      pathway, we examined the effect of AChR antagonist on brain damage and to see the
      relation between microglial activation and protective effect of AChR agonist.
      STUDY DESIGN: Seven-day-old Wistar rats were divided into 2 groups, one receiving
      AChR antagonists to see if they have deleterious effects on hypoxic-ischemic
      brain damage, and the other receiving AChR agonist, carbachol, to investigate the
      emergence of microglia in the hippocampus. Rats were subjected to left carotid
      artery ligation followed by 8% hypoxia. Brains were analyzed histologically and
      immunohistochemically. RESULTS: Antagonists of AChRs significantly enhanced brain
      damage in 1-h hypoxia-ischemia. In particular, the nicotinic AChR antagonist
      showed a marked enhancement of brain damage compared to the saline controls
      (p<0.01). The hippocampal CA1 was most vulnerable to any AChR antagonists, while
      the cortex was least vulnerable and only responsive to a higher dose of non
      selective nAChR antagonist. Carbachol showed significantly less accumulation of
      microglia in the hippocampus than the saline controls (p<0.01) in hypoxia
      ischemia. CONCLUSION: An AchR-responsive pathway in the brain plays an important
      role in modifying perinatal brain damage, in which microglial accumulation may be
      involved.

PMID- 23141186
TI  - Bilateral stenosis of carotid siphon in Hutchinson-Gilford progeria syndrome.
AB  - Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature aging disease,
      caused by a de novo mutation of lamin-A gene, LMNA G608G. Accumulation of
      abnormal lamin-A (progerin) compromises nuclear membrane integrity and results in
      the accelerated senescence. Affected patients show a typical feature of birdlike
      face, alopecia, sclerotic skin, loss of subcutaneous fat, and short stature with
      advancing years. Neonatal scleroderma is the first presentation, although early
      diagnosis is challenging. The leading cause of death is cardio-/cerebro-vascular
      accidents associated with atherosclerosis. However, not all findings may
      recapitulate the aging process. We herein report a 9-year-old Japanese male with
      HGPS who developed cerebral infarction. The genetic study of peripheral blood
      derived DNA determined a heterozygous c.1824C>T mutation, p.G608G. Telomere
      length of lymphocytes was normal. Bilateral stenosis of carotid siphons was
      prominent, while systemic arteriosclerosis was unremarkable assessed by the ankle
      brachial index, carotid ultrasound imaging and funduscopic study. HGPS patients
      have marked loss and functional defects in vascular smooth muscle cells, leading
      to the vulnerability to circulatory stress. Symmetrical stenosis of siphons might
      occur as a distinctive cerebral vasculopathy of HGPS, rather than simple vascular
      senescence. Peripheral blood study on LMNA G608G and telomere length could screen
      progerias in infancy for early therapeutic intervention. 

PMID- 23141187
TI  - Depressive and anxiety symptoms as risk factors for temporomandibular joint pain:
      a prospective cohort study in the general population.
AB  - Previous studies have associated depression and temporomandibular joint disorders
      (TMDs). The temporality, however, remains to be clarified. Most patient studies
      have selected subjects from treatment facilities, whereas in epidemiological
      studies a clinical examination has not been performed. In this study the 5-year
      follow-up data of the population-based Study of Health in Pomerania (SHIP) were
      analyzed. To estimate the effect of symptoms of depression and those of anxiety
      on the risk of TMD pain, the Composite International Diagnostic-Screener (CID-S)
      and a clinical functional examination with palpation of the temporomandibular
      joint and the masticatory muscles were used. After exclusion of subjects having
      joint pain at baseline, a sample of 3,006 Caucasian participants with a mean age
      of 49 years resulted. Of those, 122 participants had signs of TMD joint pain upon
      palpation. Subjects with symptoms of depression had an increased risk of TMD
      joint pain upon palpation (rate ratio: 2.1; 95% confidence interval: 1.5-3.0; P <
      .001). Anxiety symptoms were associated with joint and with muscle pain. The
      diagnosis, prevention, and therapy of TMD pain should also consider symptoms of
      depression and those of anxiety, and appropriate therapies if necessary.
      PERSPECTIVE: Depressive and anxiety symptoms should be considered as risk factors
      for TMD pain. Depressive symptoms are specific for joint pain whereas anxiety
      symptoms are specific for muscle pain, findings that deserve detailed
      examination. These findings may support decision-making in treating TMD.

PMID- 23141189
TI  - Inactivation of Escherichia coli by sonoelectrocatalytic disinfection using TiO2
      as electrode.
AB  - This is the first study to demonstrate sonoelectrocatalytic disinfection using
      titanium dioxide (TiO(2)) as an anode for effective inactivation of Escherichia
      coli. In brief, a non-woven TiO(2) fabric used as an anode and a platinum cathode
      were immersed in an E. coli suspension in which a positive potential was applied
      to TiO(2) concomitant with ultrasound (US) irradiation. Two control experiments
      were performed using E. coli suspensions to exhibit the effects of the
      sonoelectrocatalytic disinfection. One was disinfection by applying a positive
      potential to a TiO(2) electrode, but without US irradiation (electrochemical
      disinfection). The other was disinfection without applying a potential, but with
      US irradiation in the presence of TiO(2) (sonocatalytic disinfection). The cell
      inactivation rate in sonoelectrocatalytic disinfection was synergistically much
      more enhanced than the combined inactivation rates in electrochemical
      disinfection and sonocatalytic disinfection. This synergistically enhanced
      inactivation rate of E. coli cells was attributable to effective reaction of the
      sonocatalytically generated OH radicals with E. coli cells at the surface of the
      TiO(2) anode, which resulted from the electroadsorption of E. coli cells toward
      the TiO(2) anode.

PMID- 23141188
TI  - A meta-analytic review of the hypoalgesic effects of exercise.
AB  - The purpose of this article was to examine the effects of acute exercise on pain
      perception in healthy adults and adults with chronic pain using meta-analytic
      techniques. Specifically, studies using a repeated measures design to examine the
      effect of acute isometric, aerobic, or dynamic resistance exercise on pain
      threshold and pain intensity measures were included in this meta-analysis. The
      results suggest that all 3 types of exercise reduce perception of experimentally
      induced pain in healthy participants, with effects ranging from small to large
      depending on pain induction method and exercise protocol. In healthy
      participants, the mean effect size for aerobic exercise was moderate (d(thr) =
      .41, d(int) = .59), while the mean effect sizes for isometric exercise (d(thr) =
      1.02, d(int) = .72) and dynamic resistance exercise (d(thr) = .83, d(int) = .75)
      were large. In chronic pain populations, the magnitude and direction of the
      effect sizes were highly variable for aerobic and isometric exercise and appeared
      to depend on the chronic pain condition being studied as well as the intensity of
      the exercise. While trends could be identified, the optimal dose of exercise that
      is needed to produce hypoalgesia could not be systematically determined with the
      amount of data available. PERSPECTIVE: This article presents a quantitative
      review of the exercise-induced hypoalgesia literature. This review raises several
      important questions that need to be addressed while also demonstrating that acute
      exercise has a hypoalgesic effect on experimentally induced pain in healthy
      adults, and both a hypoalgesic and hyperalgesic effect in adults with chronic
      pain.

PMID- 23141190
TI  - Characterization of acoustic cavitation in water and molten aluminum alloy.
AB  - High-intensive ultrasonic vibrations have been recognized as an attractive tool
      for refining the grain structure of metals in casting technology. However, the
      practical application of ultrasonics in this area remains rather limited. One of
      the reasons is a lack of data needed to optimize the ultrasonic treatment
      conditions, particularly those concerning characteristics of cavitation zone in
      molten aluminum. The main aim of the present study was to investigate the
      intensity and spectral characteristics of cavitation noise generated during
      radiation of ultrasonic waves into water and molten aluminum alloys, and to
      establish a measure for evaluating the cavitation intensity. The measurements
      were performed by using a high temperature cavitometer capable of measuring the
      level of cavitation noise within five frequency bands from 0.01 to 10MHz. The
      effect of cavitation treatment was verified by applying high-intense ultrasonic
      vibrations to a DC caster to refine the primary silicon grains of a model Al-17Si
      alloy. It was found that the level of high frequency noise components is the most
      adequate parameter for evaluating the cavitation intensity. Based on this
      finding, it was concluded that implosions of cavitation bubbles play a decisive
      role in refinement of the alloy structure.

PMID- 23141191
TI  - Comparative study of ultrasound-assisted and conventional stirred dead-end
      microfiltration of grape pomace extracts.
AB  - Ultrasound (US) was used to facilitate dead-end microfiltration (MF) of grape
      pomace (GP) extracts. The effects of ultrasonic power, sonication cycle time and
      ultrasonic probe height on filtration behaviour were investigated. Ultrasonic
      irradiation had a strong impact on the MF processes, especially with high output
      power and continuous mode. A comparative study of US-assisted and stirred MF was
      performed. The energy consumption and liquid flux enhancement of the two
      filtration systems were compared. Under the same dissipation power, the flux
      enhancement is much higher for the US-assisted MF. A correlation equation for
      predicting permeate flux was derived from resistance-in-series model. The flux
      predictions were confirmed with the experimental results. Finally, the
      characteristics of permeate after US-assisted and stirred filtration were
      evaluated.

PMID- 23141192
TI  - The future of research: "leading with care".

PMID- 23141193
TI  - Patient-centered care/student-centered learning.

PMID- 23141194
TI  - Palliative care and end of life: the caregiver.
AB  - Informal caregivers are a key component of end-of-life/palliative care and are
      increasingly recognized as recipients of care. Numerous factors affect the care
      they give and they have significant care needs themselves. The purpose of this
      survey was to identify key research questions, priorities, and next steps for
      research on caregivers and palliative care. A literature search of publications
      between 2006 and 2011 was conducted, yielding 109 studies that were evaluated on
      type, quality, topic, and other factors. An interdisciplinary group of healthcare
      professionals examined results and recommended research priorities. Existing
      research is primarily descriptive in nature, with few interventions to guide
      practice. Future research priorities include factors influencing caregivers and
      roles, information and support needs, caregiver health, end-of-life issues,
      healthcare disparities, and delivery and costs of care. Conclusions include that
      expanding the science will contribute to improving caregiver performance and
      health.

PMID- 23141195
TI  - Communication and advanced care planning in palliative and end-of-life care.
AB  - Communication about and planning for the end of life has evolved with medical and
      technological changes. This article presents a focused literature review of
      Advance Directives (ADs), Advanced Care Planning (ACP), and communication in
      palliative and end-of-life care. Two focused Medline searches were conducted to
      locate articles that addressed ACP in the U.S. Content analysis was utilized to
      summarize and categorize the literature into five domains: (1) ADs, (2) ACP and
      communication, (3) Barriers to ACP, (4) Differential domains of ACP, and (5)
      Interventions to enhance the process. Policies and protocols for ACP and
      communication have been developed to facilitate the process in different patient
      populations and locations of care. Effective ACP is an essential component of
      person-centered end-of-life and palliative care.

PMID- 23141196
TI  - Psychosocial, cultural, and spiritual health disparities in end-of-life and
      palliative care: where we are and where we need to go.
AB  - Although health disparities are well documented, the extent to which they affect
      end-of-life care is unknown. Limited research funding leads to sparse and often
      contradictory palliative care literature, with few studies on causal mechanisms.
      This article explores the psychosocial, cultural, and spiritual health
      disparities existing in palliative and end-of-life care with the goal of
      identifying future research needs. This article reports efforts to determine
      knowledge gaps related to health disparities in psychosocial, cultural, and
      spiritual aspects of end-of-life care in which the authors draw upon recent
      literature from multiple databases. Although few data are available, studies show
      that minorities make little use of hospice, often because of lack of knowledge
      about hospice or palliative care, family-centered cultures, and preferences for
      more aggressive end-of-life care than hospice allows. The authors conclude that
      future research should include a search for theoretical and causal mechanisms;
      prospective longitudinal investigations; diverse patients, conditions, contexts,
      and settings; methodological diversity and rigor; and interdisciplinary,
      culturally sensitive interventions.

PMID- 23141197
TI  - The era of "e": the use of new technologies in advance care planning.
AB  - In this article, the authors review developments in technology that can help
      patients, their loved ones, and healthcare providers engage in more effective
      advance care planning (ACP). The article begins with a brief description of ACP
      and its purpose and then discusses various electronically available resources for
      ACP in the U.S. Finally the authors provide a critical assessment of the
      achievements, challenges, and future prospects for electronic advance care
      planning, or "e-planning."

PMID- 23141198
TI  - Palliative and end-of-life care research: embracing new opportunities.
AB  - The past two decades have witnessed dramatic advances in palliative and end-of
      life care research with increased understanding of the burden of life-limiting
      diseases on patients, families, clinicians, and our healthcare system; and
      researchers have documented palliative care interventions that improve patient
      and family outcomes and reduce the costs of care (Detering, Hancock, Reade, &
      Silvester, 2010). These advances have led to a new era of palliative and end-of
      life care research and practice with widespread recognition of its
      accomplishments and successes. Consequently, we now have an important opportunity
      to reassess our recent successes and challenges and to identify the goals and
      benchmarks that will ensure ongoing robust advances in this now-recognized and
      critical scientific area. High-quality palliative and end-of-life care will be
      best informed by methodologically strong research efforts that generate a body of
      evidence with the capacity to support and direct care and effect changes in
      practice. It is in this context that the National Institute of Nursing Research
      conceptualized and led a Summit titled The Science of Compassion: Future
      Directions in End-of-Life and Palliative Care Research in August, 2011. In this
      summary article, we present brief overviews of the six articles chosen for this
      Special Issue of Nursing Outlook, examine their key conclusions, articulate gaps
      and needs, and discuss next steps in palliative and end-of-life care research
      through the lens of these six topics.

PMID- 23141199
TI  - Functional outcome after non-surgical management of orbital fractures--the bias
      of decision-making according to size of defect: critical review of 48 patients.
AB  - The treatment of mild and moderate fractures of the orbital wall is
      controversial. Apart from clinical signs, the size of the defect is often used to
      aid the decision about treatment. We hypothesised that variables would be present
      that had an impact on the position and motility of the globe but were independent
      of the size of the defect, and prevented a balanced judgement of the outcome of
      conservative treatment. Between January 2000 and December 2007, 48 of 127
      patients were included in this retrospective study to analyse the functional
      outcome of orbital fractures managed without operation. Selection was dependent
      on the availability of complete clinical records, post-traumatic computed
      tomographic (CT) scans (axial and coronal sections) and ophthalmic examination.
      All 48 defects were analysed and allocated to categories of a semiquantitative
      classification. The area of fracture of each defect was calculated with an
      integral calculus or geometrical formula and correlated with the associated
      category. Category A included all orbital walls as a single unit (A1) and
      combined fracture patterns (A2 and higher). Category B described isolated
      fractures of the medial wall. There was a significant correlation between classes
      A1 and A2 (p<0.01) and absolute area of the fracture (0.98 (0.4)cm(2) and 2.42
      (0.8)cm(2)). Diplopia was most often seen in fractures in category B1 (the
      anterior third of the medial wall) and the post-traumatic position of the globe
      significantly correlated with the area of the fracture (p=0.04). The degree of
      diplopia was less severe in fractures of the posterior portion of the orbit
      (zones 2 and 3) compared with fractures of the anterior orbit, even if the defect
      was larger. The conservative management of category A1-3 and B1-3 fractures up to
      2.42 (3.15)cm(2) showed no functional impairment, provided that enophthalmos was
      less than 2mm and there was no entrapment of periorbital tissue or extraocular
      muscles. We found good correlation between enopthalmos and the size of the
      fracture, but not for diplopia or motility of the eye. We conclude that
      conservative management of an orbital fracture in which the defect is less than
      3cm(2) has a low risk of permanent functional damage if enophthalmos is less than
      2mm and entrapment of soft tissue or muscles is excluded. 

PMID- 23141200
TI  - Essential role for the mammalian ATG8 isoform LC3C in xenophagy.
AB  - In this issue, Randow and coworkers (von Muhlinen et al., 2012) report that LC3C
      plays an essential role in Salmonella clearance by interacting with the
      autophagic receptor NDP52, with consequent recruitment of all other ATG8 proteins
      to assist in the buildup of the autophagic membrane.

PMID- 23141201
TI  - Order from chaos in the nucleus.
AB  - Although it might appear that chromatin is randomly packed within the nucleus,
      recent data (Hou et al., 2012, in this issue of Molecular Cell) show that it is
      organized into defined and functionally important domains marked by preferred
      intradomain physical contacts, and with boundaries associated with insulator
      protein occupancy.

PMID- 23141202
TI  - Hazardous impact of organic arsenical compounds in chicken feed on different
      tissues of broiler chicken and manure.
AB  - The purpose of this study was to evaluate the translocation of arsenic (As) from
      feed to different tissues of broiler chicken (leg, breast, liver and heart) and
      excretory product (manure). The feed, broiler chicken and manure samples were
      collected from five selected poultry farms. The As concentrations in all samples
      were determined by electrothermal atomic absorption spectrometry, after microwave
      assisted acid digestion in closed vessels. The concentrations of As in different
      chicken feeds were found in the range of 21.3-43.7 MUg g-1. The contents of As in
      different tissues of broiler chicken, liver, muscles and heart were found in the
      range of 3.07-7.17, 2.15-5.28 and 2.11-6.36 MUg g-1, respectively, while manure
      samples contains 22.8-50.3 MUg g-1. The obtained data shows the high correlation
      coefficient between As contents in feed, excretory product or manure and tissues
      of broiler chicken in the range of r=0.41-0.83. The high level of As in excretory
      product may add toxicant to environment, on their disposal.

PMID- 23141203
TI  - Effect of administration of platelet-rich plasma in early phases of distraction
      osteogenesis: an experimental study in an ovine femur model.
AB  - BACKGROUND: It has been suggested that platelet-rich plasma (PRP) might enhance
      bone formation. The aim of this study was to quantify the effect of PRP
      administered in the early phases of distraction osteogenesis in an ovine femur
      model. METHODS: Twenty sheep aged 4 months underwent osteotomy of the femoral
      diaphysis followed by distraction osteogenesis. The sheep were divided into two
      groups of 10. One group received three injections of PRP on days 0, 10, and 20 of
      the procedure (PRP group) and the other received no additional treatment (control
      group). The results were evaluated by computed tomography (CT) and histology on
      completion of distraction osteogenesis (day 40). CT evaluation included
      measurement of the callus and bone density. Femur size was also measured
      proximally and distally. Histological evaluation was used to quantify
      osteoblasts, osteoclasts, vascular lumens, and trabecular maturity by zones and
      to calculate trabecular bone, fibrous tissue, and cartilage ratios. RESULTS:
      Radiological and histological evaluation of the regenerate bone showed no
      significant differences between the PRP group and the control group for any of
      the variables analysed. The only significant difference detected was a wider
      femur (increased diaphyseal thickness) at the proximal and distal levels in the
      PRP group. CONCLUSION: We found no radiological or histological evidence that the
      administration of PRP in the early phases of distraction osteogenesis enhances
      bone formation.

PMID- 23141204
TI  - Still no reliable consensus in management of blow-out fracture.
AB  - BACKGROUND: Management of blow-out fractures (BOF) is addressed by different
      specialties. The general agreement is that patients with the potential for late
      enophthalmus development require early surgical intervention. In this study we
      wanted to: (i) evaluate the differences in opinions between the specialties that
      manage BOF and also whether there was a difference between surgeons from
      different countries, (ii) evaluate if surgeons handle these cases based upon
      their own individual criteria,(1) (iii) evaluate the correlation between the
      management of patients with orbital floor fractures and any late sequelae
      detected upon eye examination. MATERIALS AND METHODS: Eleven patients with BOF
      were selected from the records of the Department of ENT and Head & Neck Surgery,
      Karolinska University Hospital between 2003 and 2008. The cases were presented
      with a case history and CT scans to 46 surgeons from different countries and
      specialties and they were asked to give their opinions regarding the need for
      surgery, timing of surgery and the risk for late enophthalmus. We considered a
      group of surgeons to be in agreement if there was >= 75% agreement on whether or
      not to operate, when to operate and on the risk for late enophthalmus. RESULT:
      The surgeons agreed on the choice of management for the patients (whether or not
      to operate) in only 5 of the 11 cases. Similarly, in only 5 of the 11 cases did
      the surgeons agree upon the risk for late enophthalmus. There was a greater
      difference between specialities than between physicians from the participating
      countries. CONCLUSION: There are considerable differences in opinions regarding
      the management of BOF due to a lack of a reliable consensus. The management of
      BOF appears to be based on both individual and local traditions. Guidelines based
      on a randomized prospective study in BOF are required.

PMID- 23141205
TI  - Switching Polo-like kinase-1 on and off in time and space.
AB  - Polo-like kinase (Plk)1 executes several essential functions to promote cell
      division. These functions range from centrosome maturation in late G2 phase to
      the regulation of cytokinesis, which necessitates precise separation of Plk1
      dependent substrate phosphorylation over time. Multiple levels of control are in
      place to ensure that Plk1-dependent phosphorylation of its various substrates is
      properly coordinated in time and space. Here, we review the current knowledge on
      the mechanisms that enforce the temporal and spatial control of Plk1 activity,
      and how this results in coordinated phosphorylation of its many different
      substrates. We also review a number of newly discovered functions of Plk1 that
      provide more insights into the spatiotemporal control of Plk1-dependent substrate
      phosphorylation.

PMID- 23141206
TI  - [Venous catheter-related infections].
AB  - Central venous catheter-related infections can lead to a substantial increase in
      morbidity and mortality in patients. Nowadays, with the increase in multi
      resistant bacteria, the recent appearance of new antibiotics, and the development
      of new treatment guidelines, means that this has to be constantly reviewed. The
      objective of this review is to briefly define the epidemiological and pathogenic
      concepts and to look in detail at the preventive and therapeutic measures of this
      type of infection. Practical aspects are presented of different clinical
      situations such as, antibiotic-lock of the central venous catheter, and the
      withdrawal or maintenance of the catheter.

PMID- 23141207
TI  - Care dependency independently predicts two-year survival in outpatients with
      advanced chronic organ failure.
AB  - OBJECTIVE: Previous studies suggest that care dependency may predict survival in
      hospitalized patients, but the prognostic value of care dependency in clinically
      stable outpatients with advanced chronic organ failure remains unknown. The
      objective of this study was to assess whether and to what extent care dependency
      predicts 2-year survival in patients with advanced chronic organ failure. DESIGN:
      Longitudinal observational study. SETTING: Patients were recruited at the
      outpatient clinic of one academic and six general hospitals in The Netherlands.
      PARTICIPANTS: A total of 265 clinically stable outpatients with advanced chronic
      obstructive pulmonary disease (n = 105), chronic heart failure (n = 80), and
      chronic renal failure (n = 80) were included at baseline. MEASUREMENTS: Care
      dependency was assessed using the Care Dependency Scale (CDS), a 15-item self
      administered questionnaire. In addition, patients performed a Timed Up and Go
      test to assess mobility. Finally, demographics, clinical characteristics, and 2
      year survival were recorded. RESULTS: At baseline, 116 patients (43.8%) reported
      a CDS score <= 68 points and were considered as care dependent. In total, 66
      patients (24.9%) died within 2 years. The Cox regression model showed that a
      higher CDS score (lower level of care dependency) was associated with a lower
      probability of dying within 2 years (hazard ratio, 0.95; 95% CI: 0.90-0.97),
      whereas older age was associated with a greater probability of dying within 2
      years (hazard ratio, 1.06; 95% CI, 1.03-1.09). CONCLUSION: The level of care
      dependency independently predicts 2-year survival among clinically stable
      outpatients with advanced chronic organ failure. Therefore, regular assessment of
      the level of care dependency should be included in clinical care for patients
      with advanced chronic organ failure.

PMID- 23141208
TI  - Re-emergence of posttraumatic stress disorder nightmares with nursing home
      admission: treatment with prazosin.
AB  - Seniors with a history of emotional trauma decades earlier can experience a
      recurrence of posttraumatic stress disorder symptoms when transitioning to a
      nursing home. We present the case of an 86-year-old male Holocaust survivor
      admitted to a nursing home for physical therapy and rehabilitation 6 weeks after
      the death of his wife; the patient was expressing a persistent death wish.
      Despite the multiple risk factors for depression, his distress was specifically
      related to the reemergence of nightly posttraumatic nightmares. Over the course
      of 1 week of treatment with 1 mg prazosin at bedtime, his nightmares and his
      death wish completely resolved. He achieved his rehabilitation goals and was
      discharged to a community setting. This report highlights the importance of
      considering posttraumatic stress disorder in nursing home residents with a
      history of emotional trauma, and understanding how to address these symptoms
      pharmacologically and nonpharmacologically.

PMID- 23141209
TI  - The psychophysics of transition to long term care.
AB  - More than a decade after the publication of To Err Is Human, cognitive error
      remains a mystery to physicians. Competent and conscientious physicians rarely
      recall making a single cognitive error, yet this must be central to the
      explanation for inappropriate physician nonadherence to evidence-based
      guidelines. Published information regarding cognitive error in the medical
      literature is scarce and widely scattered. We do know that cognitive error is
      induced by complexity, duress, and uncertainty, conditions that regularly
      confront long term care physicians when they assume care of a new patient at the
      skilled nursing facility. Negative attitudes and low expectations of care are
      common among new patients and families. This is compounded when care is assumed
      by an unfamiliar physician. The initial disquiet and negative misconceptions of
      patients and families regularly make the transition one of the most error-prone
      events in medical practice. On the brighter side, the transition provides an
      excellent opportunity to study cognitive error. Cognitive errors at transition
      typically begin with a decision to avoid mention of necessary changes to flawed
      treatment plans already in effect. This is done as a temporary measure to avoid
      further stressing the patient and family. But what appears to be an ideal
      compromise is a risky option and should be avoided. Evading the issue introduces
      long-term risk to the patient. In addition, although it is seldom acknowledged,
      evading change often has a negative impact on local standards of care. Five
      cognitive principles are presented as root causes of cognitive error. Six
      contextual factors are identified that are endemic to nursing home practice,
      making the physician even more error prone. Because mistrust is central to
      dysfunctional decision making at the transition, strategies are presented to
      expedite gaining trust. This article makes the case for adding training in the
      cognitive psychology of medical decision making to core requirements for
      certification in medical direction.

PMID- 23141210
TI  - What factors contribute to successful appeals of nursing homes' deficiencies in
      the informal dispute resolution process?
AB  - OBJECTIVES: To determine what factors contribute to successful appeals of nursing
      home deficiencies in the Informal Dispute Resolution (IDR) process. DESIGN: We
      merged Centers for Medicare and Medicaid Services' data about IDRs with Online
      Survey, Certification, and Reporting data about nursing home characteristics. We
      performed multivariate statistical analyses to predict successful appeals as a
      function of characteristics of the deficiency being appealed, the survey that
      triggered the deficiency, characteristics of the nursing home, and the state.
      SETTING: All nursing homes nationally in the period 2005-2008. MEASUREMENTS:
      Successful appeals were defined as those in which the deficiency was removed or
      its severity or scope reduced. Independent variables included the Centers for
      Medicare and Medicaid Services' measures of severity and scope of deficiency,
      abuse and neglect, substandard care, total number of deficiencies in the survey,
      whether the IDR was triggered by a survey or complaint, facility ownership and
      reputation, and state stringency of regulation. RESULTS: Twenty-six percent of
      submitted IDRs were successful in 2005-2008. Success was more likely for less
      severe deficiencies, when deficiencies were triggered by a survey rather than a
      complaint, and when fewer deficiencies were included in the appeal. Facility
      ownership and state stringency of regulation were not significantly associated
      with the IDR success. DISCUSSION: Overall, 2.6% of deficiencies issued were
      overturned through the IDR process. Further study is required to determine the
      appropriateness of these overturned cases and the opportunities they offer to
      improve the survey process.

PMID- 23141211
TI  - Prevalence and spread of multidrug resistant Escherichia coli isolates among
      nursing home residents in the southern part of The Netherlands.
AB  - OBJECTIVES: Empiric antibiotic treatment should be based on recent surveillance
      data. Therefore, we conducted a surveillance of (multidrug) resistance of
      Escherichia coli and antibiotic use among Dutch nursing home (NH) residents.
      Pulsed-field gel electrophoresis and multilocus sequence typing were used to
      describe the spread of multidrug-resistant strains. DESIGN: Observational study.
      SETTING: Five NHs in the southern part of The Netherlands. PARTICIPANTS: A total
      of 337 NH residents from both somatic and psychogeriatric wards. MEASUREMENTS:
      The prevalence and spread of antibiotic resistance and multidrug resistant E.
      coli isolates collected from urine samples and antibiotic use among the NH
      residents were investigated. RESULTS: A total of 208 E. coli isolates were
      collected from 308 urine samples. Resistance to amoxicillin-clavulanic acid was
      23% and resistance to ciprofloxacin was 16%. Resistance to trimethoprim
      sulfamethoxazole was 19%, whereas nitrofurantoin resistance was less than 1%.
      Multidrug resistance was observed in 28 of the 208 isolates (13%). Several
      isolates showed a similar pulsed-field gel electrophoresis pulsotype and
      multilocus sequence typing type. Sequence type (ST) 131 was the most prevalent
      (48%) and was demonstrated in all NHs and with four different pulsotypes.
      Consumption of antibiotics for systemic use was 64.4 defined daily dose
      (DDD)/1000 residents/day. Amoxicillin-clavulanic acid was most frequently
      prescribed (20.92 DDD/1000 residents/day), followed by the quinolones (14.8
      DDD/1000 residents/day). CONCLUSION: We observed a high prevalence of antibiotic
      resistance and antibiotic use. In particular, the use of and resistance to
      fluoroquinolones is concerning. Because of the high prevalence of resistance,
      many agents are no longer suitable for empiric treatment. E. coli ST131, which
      has also been demonstrated in this study, poses a potential risk to this
      vulnerable population. We have clearly demonstrated that the resistance among NH
      residents is different from elderly living at home and hospitalized patients, and
      with the emergence of resistant strains, such as ST131, NHs are a potential
      reservoir for multidrug resistant bacteria.

PMID- 23141212
TI  - Can a semi-automated surface matching and principal axis-based algorithm
      accurately quantify femoral shaft fracture alignment in six degrees of freedom?
AB  - Accurate alignment of femoral shaft fractures treated with intramedullary nailing
      remains a challenge for orthopaedic surgeons. The aim of this study is to develop
      and validate a cone-beam CT-based, semi-automated algorithm to quantify the
      malalignment in six degrees of freedom (6DOF) using a surface matching and
      principal axes-based approach. Complex comminuted diaphyseal fractures were
      created in nine cadaveric femora and cone-beam CT images were acquired (27 cases
      total). Scans were cropped and segmented using intensity-based thresholding,
      producing superior, inferior and comminution volumes. Cylinders were fit to
      estimate the long axes of the superior and inferior fragments. The angle and
      distance between the two cylindrical axes were calculated to determine
      flexion/extension and varus/valgus angulation and medial/lateral and
      anterior/posterior translations, respectively. Both surfaces were unwrapped about
      the cylindrical axes. Three methods of matching the unwrapped surface for
      determination of periaxial rotation were compared based on minimizing the
      distance between features. The calculated corrections were compared to the input
      malalignment conditions. All 6DOF were calculated to within current clinical
      tolerances for all but two cases. This algorithm yielded accurate quantification
      of malalignment of femoral shaft fractures for fracture gaps up to 60 mm, based
      on a single CBCT image of the fractured limb.

PMID- 23141213
TI  - Erythropoietin induces insulin-like growth factor-1 from three-dimensional
      culture of human dermal papilla cells.

PMID- 23141215
TI  - HER-2 expression in canine morphologically normal, hyperplastic and neoplastic
      mammary tissues and its correlation with the clinical outcome.
AB  - The proto-oncogene HER-2/neu (c-erbB-2) encodes a transmembrane receptor protein
      with tyrosine-kinase activity. Previous studies have shown that HER-2 protein
      over-expression is present in canine mammary tumours, however, possible
      prognostic and predictive analogies between protein over-expression patterns in
      canine and human species are still controversial. Thirty-five canine mammary
      carcinomas, 11 mammary adenomas, and normal, hyperplastic or dysplastic tissues
      taken at the marginal area of the tumours were evaluated by immunohistochemistry
      (IHC) for HER-2 expression, using the Hercept Test(r) system scoring guidelines.
      HER-2 over-expression was detected in 3/11 adenomas and 10/35 carcinomas. Normal,
      hyperplastic and dysplastic mammary tissues were also found to be positive. The
      correlations between HER-2 expression and tumour histological grading, mitotic
      index, the presence of lymphatic invasion, and overall survival (OS) were
      evaluated. In carcinomas, HER-2 positive status only correlated with the mitotic
      index. A positive correlation was also found between HER-2 positive status and
      the presence of HER-2 over-expression in normal, hyperplastic or/and dysplastic
      mammary tissues surrounding the tumours. The percentage of HER-2 over-expressing
      tumours was similar to the percentage previously observed in canine benign and
      malignant mammary tumours. However an investigation regarding morphologically
      normal and hyperplastic or dysplastic tissues surrounding neoplastic lesions also
      showed HER-2 over-expression. In contrast with human mammary tumours, this study
      confirmed that in canine species, HER-2 over-expression does not identify a
      subgroup of tumours with a poor prognosis. In fact, we found HER-2 over
      expression in morphologically non-neoplastic mammary tissues, surrounding
      hyperplastic and neoplastic lesions.

PMID- 23141214
TI  - The assessment of data mining for the prediction of therapeutic outcome in 3719
      Egyptian patients with chronic hepatitis C.
AB  - INTRODUCTION: Decision-tree analysis; a core component of data mining analysis
      can build predictive models for the therapeutic outcome to antiviral therapy in
      chronic hepatitis C virus (HCV) patients. AIM: To develop a prediction model for
      the end virological response (ETR) to pegylated interferon PEG-IFN plus ribavirin
      (RBV) therapy in chronic HCV patients using routine clinical, laboratory, and
      histopathological data. PATIENTS AND METHODS: Retrospective initial data (19
      attributes) from 3719 Egyptian patients with chronic HCV presumably genotype-4
      was assigned to model building using the J48 decision tree-inducing algorithm
      (Weka implementation of C4.5). All patients received PEG-IFN plus RBV at Cairo
      Fatemia Hospital, Cairo, Egypt in the context of the national treatment program.
      Factors predictive of ETR were explored and patients were classified into seven
      subgroups according to the different rates of ETR. The universality of the
      decision-tree model was subjected to a 10-fold cross-internal validation in
      addition to external validation using an independent dataset collected of 200
      chronic HCV patients. RESULTS: At week 48, overall ETR was 54% according to
      intention to treat protocol. The decision-tree model included AFP level (<8.08
      ng/ml) which was associated with high probability of ETR (73%) followed by stages
      of fibrosis and Hb levels according to the patients' gender followed by the age
      of patients. CONCLUSION: In a decision-tree model for the prediction for
      antiviral therapy in chronic HCV patients, AFP level was the initial split
      variable at a cutoff of 8.08 ng/ml. This model could represent a potential tool
      to identify patients' likelihood of response among difficult-to-treat presumably
      genotype-4 chronic HCV patients and could support clinical decisions regarding
      the proper selection of patients for therapy without imposing any additional
      costs.

PMID- 23141216
TI  - Re: VEGF pathway genetic variants as biomarkers of treatment outcome with
      bevacizumab: an analysis of data from the AViTA and AVOREN randomised trials.

PMID- 23141217
TI  - Re: Primary renal cell carcinoma: relationship between 18F-FDG uptake and
      response to neoadjuvant sorafenib.

PMID- 23141218
TI  - Re: A Phase 2 trial of sunitinib in patients with advanced non-clear cell renal
      cell carcinoma.

PMID- 23141219
TI  - Re: Two phase 2 trials of the novel Akt inhibitor perifosine in patients with
      advanced renal cell carcinoma after progression on vascular endothelial growth
      factor-targeted therapy.

PMID- 23141220
TI  - Re: Safety and activity of anti-PD-L1 antibody in patients with advanced cancer.

PMID- 23141221
TI  - Re: Antitumor activity and safety of tivozanib (AV-951) in a phase II randomized
      discontinuation trial in patients with renal cell carcinoma.

PMID- 23141222
TI  - Re: Neoadjuvant and adjuvant chemotherapy for locally advanced bladder carcinoma:
      development of novel bladder preservation approach, osaka medical college
      regimen.

PMID- 23141224
TI  - Re: Radical prostatectomy versus observation for localized prostate cancer.

PMID- 23141225
TI  - Re: Projecting prostate cancer mortality in the PCPT and REDUCE chemoprevention
      trials.

PMID- 23141226
TI  - Re: A population-based assessment of germline HOXB13 G84E mutation and prostate
      cancer risk.

PMID- 23141228
TI  - Re: Technical refinement and learning curve for attenuating neuropraxia during
      robotic-assisted radical prostatectomy to improve sexual function.

PMID- 23141229
TI  - Re: Understanding variation in primary prostate cancer treatment within the
      Veterans Health Administration.

PMID- 23141230
TI  - Re: Intensity-modulated radiation therapy, proton therapy, or conformal radiation
      therapy and morbidity and disease control in localized prostate cancer.

PMID- 23141231
TI  - Re: Incidence of second malignancies after external beam radiotherapy for
      clinical stage I testicular seminoma.

PMID- 23141232
TI  - Re: Chronic prostatitis does not influence urinary PCA3 score.

PMID- 23141233
TI  - Wound healing and infection in surgery: the pathophysiological impact of smoking,
      smoking cessation, and nicotine replacement therapy: a systematic review.

PMID- 23141234
TI  - Re: Past history of skin infection and the risk of surgical site infection after
      elective surgery.

PMID- 23141235
TI  - Re: A new diagnostic algorithm for antibody-mediated microcirculation
      inflammation in kidney transplants.

PMID- 23141236
TI  - Re: The effects of ambient temperature, humidity and season of year on urine
      composition in patients with nephrolithiasis.

PMID- 23141237
TI  - Re: Prevalence of kidney stones in the United States.

PMID- 23141239
TI  - Re: Comparison of renal function and metabolic abnormalities of cystine stone
      patients and calcium oxalate stone patients in China.

PMID- 23141238
TI  - Re: The impact of dietary calcium and oxalate ratios on stone risk.

PMID- 23141240
TI  - Re: Surgery for primary hyperparathyroidism: are the consensus guidelines being
      followed?

PMID- 23141242
TI  - Re: Risk factors for perinephric hematoma formation after shock wave lithotripsy:
      a matched case-control analysis.

PMID- 23141244
TI  - Re: Diagnostic yield of CT urography in the evaluation of young adults with
      hematuria.

PMID- 23141245
TI  - Re: CT-based determination of maximum ureteral stone area: a predictor of
      spontaneous passage.

PMID- 23141246
TI  - Re: Reconstruction of distal urethral strictures confined to the glans with
      circular buccal mucosa graft.

PMID- 23141247
TI  - Re: Unsuccessful outcomes after posterior urethroplasty: definition, diagnosis,
      and treatment.

PMID- 23141248
TI  - Re: The clinical spectrum of the presenting signs and symptoms of anterior
      urethral stricture: detailed analysis of a single institutional cohort.

PMID- 23141249
TI  - Re: Urethroplasty after radiation therapy for prostate cancer.

PMID- 23141250
TI  - Re: Kidney volume changes in patients with autosomal dominant polycystic kidney
      disease after renal transplantation.

PMID- 23141251
TI  - Re: Guidelines for providing privileges and credentials to physicians for
      transvaginal placement of surgical mesh for pelvic organ prolapse.

PMID- 23141252
TI  - Re: The efficacy and safety of PSD503 (phenylephrine 20%, w/w) for topical
      application in women with stress urinary incontinence. a phase II, Multicentre,
      double-blind, placebo controlled, 2-way cross over study.

PMID- 23141253
TI  - Re: Urethral injection therapy for urinary incontinence in women.

PMID- 23141254
TI  - Re: The clinical relevance of cell-based therapy for the treatment of stress
      urinary incontinence.

PMID- 23141255
TI  - Re: Can maximum urethral closure pressure (MUCP) be used to predict outcome of
      surgical treatment of stress urinary incontinence?

PMID- 23141256
TI  - Re: High prevalence of pelvic floor muscle dysfunction in hospitalized elderly
      women with urinary incontinence.

PMID- 23141257
TI  - Re: Brain activity underlying impaired continence control in older women with
      overactive bladder.

PMID- 23141258
TI  - Re: Lower urinary tract symptoms and urinary incontinence in a geriatric cohort:
      a population-based analysis.

PMID- 23141259
TI  - Re: Long-term clinical outcomes of the tension-free vaginal tape procedure for
      the treatment of stress urinary incontinence in elderly women over 65.

PMID- 23141260
TI  - Re: Spectrum of urodynamic abnormalities and renal function changes in adult men
      with non-neurogenic urinary retention.

PMID- 23141261
TI  - Re: The efficacy of in-and-out catheterization as a way of trial without
      catheterization strategy for treatment of acute urinary retention induced by
      benign prostate hyperplasia: variables predicting success outcome.

PMID- 23141262
TI  - Re: Combination of channel-TURP and ILC versus standard TURP or ILC for elderly
      with benign prostatic hyperplasia: a randomized prospective trial.

PMID- 23141263
TI  - Re: Trends and attitudes in surgical management of benign prostatic hyperplasia.

PMID- 23141264
TI  - Re: Impact of frequency of intercourse on erectile dysfunction: a cross-sectional
      study in Wuhan, China.

PMID- 23141265
TI  - Re: Sexual function in pre- and post-menopausal women with obstructive sleep
      apnea syndrome.

PMID- 23141267
TI  - Re: A National study of adverse effects and global quality of life among
      candidates for curative treatment for prostate cancer.

PMID- 23141268
TI  - Re: Prostate cancer diagnosis is associated with an increased risk of erectile
      dysfunction after prostate biopsy.

PMID- 23141269
TI  - Re: Laparoendoscopic single-site surgery versus conventional laparoscopic
      varicocele ligation in men with palpable varicocele: a randomized, clinical
      study.

PMID- 23141270
TI  - Re: Low-dose lisinopril in normotensive men with idiopathic oligospermia and
      infertility: a 5-year randomized, controlled, crossover pilot study.

PMID- 23141271
TI  - Re: The effects of male age on sperm analysis by motile sperm organelle
      morphology examination (MSOME).

PMID- 23141272
TI  - Re: Molecular cytogenetic and genetic aspects of globozoospermia: a review.

PMID- 23141273
TI  - Re: Mild induced testicular and epididymal hyperthermia alters sperm chromatin
      integrity in men.

PMID- 23141274
TI  - Re: the Incidence and effect of bacteriospermia and elevated seminal leukocytes
      on semen parameters.

PMID- 23141275
TI  - Re: Management of lower urinary tract dysfunction: a stepwise approach.

PMID- 23141276
TI  - Re: Augmentation cystoplasty in children without preoperative mechanical bowel
      preparation.

PMID- 23141278
TI  - Re: Mini-vesicostomy in the management of PUV after valve ablation.

PMID- 23141277
TI  - Re: Effectiveness of biofeedback for dysfunctional elimination syndrome in
      pediatrics: a systematic review.

PMID- 23141279
TI  - Re: A unifying model for mTORC1-mediated regulation of mRNA translation.

PMID- 23141280
TI  - Re: VHL-Regulated miR-204 suppresses tumor growth through inhibition of LC3B
      mediated autophagy in renal clear cell carcinoma.

PMID- 23141281
TI  - Re: Orthotopic grafting of cryopreserved prepubertal testicular tissue: in search
      of a simple yet effective cryopreservation protocol.

PMID- 23141282
TI  - Re: Increased bladder activity is associated with elevated oxidative stress
      markers and proinflammatory cytokines in a rat model of atherosclerosis-induced
      chronic bladder ischemia.

PMID- 23141283
TI  - [A comparison of the effectiveness of five types of hemostatic surgeries for
      intractable postpartum haemorrhage and the factors of failed hemostasis].
AB  - OBJECTIVE: To study the different clinical effects of using 5 kinds of hemostatic
      surgeries to manage the intractable postpartum hemorrhage and analyse the risk
      factors of failed hemostasis. METHODS: From Jan. 2007 to Jul. 2011, 96 patients
      with intractable postpartum hemorrhage were studied retrospectively and grouped
      by the first step surgical treatment. The hemostatic surgeries included uterine
      tamponade (tamponade group), pelvic blood vessels ligation (ligation group),
      pelvical arterial embolization (embolization group), uterine compression sutures
      (sutures group) and uterine compression sutures combining tamponade (combined
      group). The intraoperative and postoperation datum were compared among groups, so
      dose the treatment outcomes. Multivariate analysis were used for failed
      hemostasis. RESULTS: (1) The blood loss of 96 patients ranged from 1200 to 9100
      ml, and 71 patients had a succeed hemoatasis after employing these surgeries and
      25 failed. (2) The blood loss before hemostasis surgeries in tamponade group and
      embolization group was statistically greater than in sutures group (P < 0.05).
      Blood loss during the hemostasis surgeries in ligation group was statistically
      greater than in embolization and sutures groups (P < 0.05). The operating time of
      embolization group was statistically shorter than ligation group, sutures group
      and the combined group (P < 0.05). (3) Fine of 96 patients had uterine atony and
      43 had a successful hemostasis with the success rate about 78%. Forty-six had
      placenta previa and 39 success with success rate 85%. Thirty-three had placenta
      accrete and 13 of which succeed in hemostasis with success rate about 39%. In
      patients with uterine atony and placenta previa, the difference of hemostasis
      rate in groups had no statistically significant (P > 0.05). In patients with
      placenta accrete, the hemostasis rate in embolization group was higher than in
      others groups (P < 0.01). (4) The multivariate analysis found that scar uterus,
      placenta accrete and coagulation defects were the risk factors of failed
      hemotasis. The OR value respectively was 2.9 (95%CI: 1.1 - 7.6), 17.9 (95%CI: 5.6
      - 56.3) and 16.2 (95%CI: 3.2 - 83.5). Embolization had some extent of protective
      effection (OR = 0.9, 95%CI: 0.8 - 0.9). CONCLUSIONS: (1) Five kinds of hemostatic
      surgeries were all effective. Though the success rate among groups did show
      statistical difference, pelvical arterial embolization has the comparative
      advantage of shorter operating time, less operating blood loss and higher success
      rate in placenta accrete. (2) Since scar uterus, placenta accrete and coagulation
      defects were the risk factors of failed hemostasis, sufficient preparation should
      be made for patients with these risk factors and the hemostatic surgeries should
      be choosed individually.

PMID- 23141284
TI  - [Investigation into the clinical suitability of Institute of Medicine 2009
      guidelines regarding weight gain during pregnancy for women with full term
      singleton fetus in China].
AB  - OBJECTIVE: To study whether the current Institute of Medicine (IOM) pregnancy
      weight gain recommendations vary by pre-pregnancy body mass index (BMI) was
      suitable to Chinese people. METHODS: A study was conducted on 4736 term singleton
      live birth gravidas, who were diagnosed normal glucose metabolism and delivered
      in Peking University First Hospital in 2005 and 2009, by reviewing the medical
      records. Based on the pre-pregnant BMI, the selected cases were divided into 3
      groups: low body mass group (BMI < 18.5 kg/m(2), n = 465), normal body mass group
      (BMI 18.5 - 24.9 kg/m(2), n = 3549), over body mass group (BMI >= 25 kg/m(2), n =
      722). All the cases were divided into 3 subgroups based on pregnancy weight gain
      as below, within, and above the IOM recommendations in each pre-pregnant BMI
      group. Totally 4736 newborns were divided by birth weight into 3 groups: normal
      birth weight group (weight 2500 - 4000 g, n = 4339), macrosomia group (weight >=
      4000 g, n = 359) and low birth weight group (weight < 2500 g, n = 38). The
      difference of age, gestational age, pre-pregnant weight, pre-pregnant BMI and
      history of delivery of cases between 2005 and 2009 were analyzed. The difference
      of pregnancy outcome of women whose gestational weight gain was below, within,
      and above the IOM recommendations was analyzed. RESULTS: (1) Compared to mothers
      with pregnancy weight gain within IOM recommendations in low body mass group,
      risk of low birth weight in offspring was elevated tendency with pregnancy weight
      gain below IOM recommendations (OR = 3.71, 95%CI: 0.97 - 14.12, P = 0.055). (2)
      In normal body mass group, compared to women with pregnancy weight gain within
      IOM recommendations, risk of macrosomia in offspring was elevated with pregnancy
      weight gain above IOM recommendations (OR = 2.14, 95%CI: 1.62 - 2.83, P < 0.01).
      (3) In over body mass group, compared to women with pregnancy weight gain within
      IOM recommendations, risk of macrosomia in offspring was elevated (OR = 3.25,
      95%CI: 1.65 - 6.39, P = 0.001) and risk of hypertensive disorders complicating
      pregnancy was high (OR = 1.79, 95%CI: 1.04 - 3.09, P = 0.037) in women with
      pregnancy weight gain above IOM recommendations. CONCLUSION: The current IOM
      pregnancy weight gain recommendations vary by pre-pregnancy BMI may be suitable
      to Chinese people.

PMID- 23141285
TI  - [Pregnancy outcomes of eight pregnant women with congenital adrenal hyperplasia
      due to 21-hydroxylase deficiency].
AB  - OBJECTIVE: To investigate the clinical features and pregnant outcomes of the
      pregnant women with congenital adrenal hyperplasia (CAH) 21-hydroxylase
      deficiency (21-OHD). METHODS: The clinical features, therapies, pregnant outcomes
      of the pregnant women with 21-OHD were retrospectively reviewed in Peking Union
      Medical College Hospital, from January 2005 to April 2011. RESULTS: There were 8
      pregnant women with 21-OHD including 5 simple virilizing patients and 3
      nonclassical 21-OHD women. Eight patients were accepted progestational and
      prenatal continual lower glucocorticoid treatment. During the gestational period,
      the dosage of glucocorticoid was adjusted in one pregnancy. The serum level of 17
      alpha hydroxyprogesterone (17-OHP) were elevated after pregnancy [(70 +/- 38)
      versus (24 +/- 23) nmol/L, P < 0.05]. The fertility and offspring rate of 8
      patients was 8/12, the fertility and offspring rate of patients who started
      treatment at preadolescence was significantly increased (4/5 versus 4/7). Four
      patients were accepted genital reconstructive surgery (clitorectomy,
      clitoroplasty, vulvoplasty) before pregnancy. The incidence of GDM was 1/8. All
      patients selected caesarean at from 37(+6) gestation weeks to 39(+6) gestation
      weeks. The average newborn birth weight was (3210 +/- 447) g, and height was (48
      +/- 2) cm of 8 neonates, none of them was CAH. CONCLUSIONS: Medical and surgical
      therapy provides satisfactory fertility and pregnancy outcomes for women with 21
      OHD. It is safe to pregnant women with 21-OHD and their fetus in continual lower
      glucocorticoid treatment. The dosage of glucocorticoid should be carefully
      adjusted during the pregnancy individually according to serum level of 17-OHP.

PMID- 23141286
TI  - [Study on the incidence and influences on ectopic pregnancy from embryo transfer
      of fresh cycles and frozen-thawed cycles].
AB  - OBJECTIVE: To investigate ectopic pregnancy from embryo transfer (ET)of in-vitro
      fertilization (IVF) cycle and intracytoplasmic sperm injection (ICSI) cycle and
      frozen-thawed (FET) cycle. METHODS: From Jan.2005 to Dec. 2010, a total of 9037
      IVF-ET or ICSI-ET cycles and 4034 FET cycles were performed in our reproductive
      medicine center, Affiliated First Hospital of Zhengzhou University. The incidence
      of ectopic pregnancy rate was studied in fresh cycles IVF-ET (5998) and ICSI-ET
      (3039) cycles, and natural FET (2198) and hormone replacement (E-P) FET (1836)
      cycles. RESULTS: Of 4034 FET cycles, 1090 clinical pregnancies and 26 ectopic
      pregnancies were observed, the incidence of ectopic pregnancy was 2.38%
      (26/1090). Of 9037 fresh cycles, 3602 cycles were clinical pregnancy, and 133
      cycles were ectopic pregnancy, and the incidence of ectopic pregnancy was 3.69%
      (133/3602). The ectopic pregnancy rate in FET cycles was lower than in fresh
      cycles significantly (P < 0.05). Of 3039 fresh ICSI-ET cycles, the incidence of
      ectopic pregnancy was 2.62% (34/1298) in 1298 clinical pregnancies. Of 5998 IVF
      ET cycles, 2304 clinical pregnancies were observed, the incidence of ectopic
      pregnancy was 4.30% (99/2304). Ectopic pregnancy rate in the fresh ICSI-ET cycles
      was lower than that of IVF-ET group significantly (P < 0.01). The ectopic
      pregnancy rate in the natural FET cycles was 1.46% (8/547), which was
      significantly lower than 3.31% (18/543) in E-P group (P < 0.05). CONCLUSIONS: The
      incidence of ectopic pregnancy of FET cycles was significantly lower than that of
      fresh embryo transfer cycles. The application of exogenous sex hormones in
      assisted reproductive cycles might increase occurrence of ectopic pregnancy.

PMID- 23141287
TI  - [Therapeutic effect of metformin for clomiphene-resistant infertility patients
      with polycystic ovary syndrome: a systematic analysis].
AB  - OBJECTIVE: To evaluate the efficacy of metformin (MTF) in treatment of clomiphene
      (CC)-resistant patients with polycystic ovary syndrome (PCOS). METHODS: The
      published articles of randomized controlled trial (RCT) of comparison of MTF
      combined with CC and CC alone in treatment of CC-resistant PCOS were searched in
      PubMed, EMBASE, OVID, EBSCO databases and Cochrane Library, and these studies
      were screened under inclusion and exclusion criteria. The quality of included
      studies and extract data of comparison of ovulation rates and pregnancy rates
      were evaluated. And the Meta-analysis using statistic software RevMan 5.0 was
      completed. RESULT: Total of 333 patients in total 8 trials were included. Meta
      analysis showed that MTF plus CC led to a significantly higher clinical ovulation
      rate (OR = 7.31, 95%CI: 2.57 - 20.76, P < 0.05) and pregnancy rate (OR = 7.93,
      95%CI: 2.45 - 25.63, P < 0.05) than that of CC alone. CONCLUSION: MTF can
      increase ovulation and pregnancy rates of CC-resistant PCOS women.

PMID- 23141288
TI  - [Prospective study on total pelvic reconstruction surgery with Prosima in the
      treatment of pelvic organ prolapse stage III].
AB  - OBJECTIVE: To evaluate the safety and efficacy of total pelvic reconstruction
      surgery with Prosima in treatment of pelvic organ prolapse (POP) stage III.
      METHODS: From July 2010 to December 2011, 31 patients with POP stage III
      undergoing total pelvic reconstruction surgery with Prosima were enrolled in this
      prospective study. Among two cases complicated with stress urinary incontinence
      underwent transobturator tension-free vaginal tape concomitantly with total
      pelvic reconstruction surgery with Prosima. Clinical parameters during peri
      operation were recorded and compared. Pelvic organ prolapse quantitative
      examination (POP-Q) and anatomic improvement in these patients after surgery were
      analyzed. Comparisons of pelvic floor impact questionnaire-short form 7 (PFIQ-7)
      and pelvic organ prolapse-urinary incontinence sexual questionnaire-short form 12
      (PISQ-12) in these patients before and after surgery were used to evaluate
      quality of life and quality of sexual life. RESULTS: The mean operating time was
      (55 +/- 13) minutes, mean blood loss was (66 +/- 25) ml. No severe intraoperative
      complications were observed. All patients were able to recover spontaneous
      micturation within 5 days. Two cases experienced pelvic hematoma with diameters
      less than 7 cm, and resolved later. Another case was urinary tract infection. At
      the median follow-up 6 months (1 - 15 months), the rate of anatomic success
      defined as the leading vaginal edge above the hymen was 94% (29/31). There were
      significant improvements in Aa, Ba, Ap, Bp, and C (P < 0.01) by POP-Q. Two
      patients showed recurrent prolapse at 3 months and 1 year after surgery, without
      the need of further operation. The median score of post-operative PFIQ-7 was 0
      point at 6 months and 0 point at 12 months after operation, respectively, which
      were significantly lower than that of 50 points pre-operation (P < 0.01). And
      there was no significant difference in the average score of PISQ-12 before and
      after surgery [(30 +/- 6) points versus (31 +/- 4) points] (P > 0.05). The rate
      of mesh exposure was 16% (5/31), all the 5 cases occurred within 6 months and was
      cut in clinic. There was no case of de novo urinary incontinence and de novo
      dyspareunia. CONCLUSIONS: Pelvic reconstruction surgery with Prosima is safe and
      efficacy in treatment of POP stage III. It could improve quality of life
      remarkably without influence on sexual quality of life.

PMID- 23141289
TI  - [Analysis of mesh related complications after trans-vaginal mesh-augmented pelvic
      floor reconstruction surgery].
AB  - OBJECTIVE: To evaluate the complications after trans-vaginal mesh-augmented
      pelvic floor reconstruction in treatment of pelvic organ prolapse (POP). METHODS:
      From February 2007 to October 2009, vaginal mesh procedures were performed on 91
      women with POP stage III-IV in Peking University Third Hospital. The operative
      complications were studied. RESULTS: Ninety patients underwent successful surgery
      among 91 patients. Follow-up rate was 94% (85/90) at a median follow-up of 28.4
      (15 - 44) months. One patient underwent intraoperative organ injuries, and 10
      patients had postoperation mesh-related complications. The rate of mesh-related
      complications was 2% (2/85), 2% (2/85), 4% (3/85), 4% (3/85) on 6, 6 - 12, 12 -
      24 and more than 24 months following up, respectively. Seven patients underwent
      conservative treatment and the symptoms were improved. Three patients underwent
      the second surgery, and the symptoms were cured or relieved. CONCLUSION: The
      incidence of mesh-related complications was low, and interventions were effective
      in vaginal mesh procedure.

PMID- 23141290
TI  - [Serum changes of adiponectin, insulin resistance and their correlation in
      endometrial cancer patients].
AB  - OBJECTIVE: To explore changes of serum adiponectin and insulin resistance in
      patients with endometrial cancer and to evaluate the clinical significance and
      correlation. METHODS: The serum levels of adiponectin and fasting insulin were
      determined by ELISA, electro-chemilluminometry and radioimmunoassay in 35
      patients with endometrial cancer [all patients divided into two groups, A1 group
      belonged to without postmenopausal when first visiting (n = 20), A2 group
      belonged to postmenopausal when first visiting (n = 15)] and 30 cases of health
      control. The result of homeostasis model assessment-insulin resistance (HOMA-IR)
      index was calculated. RESULTS: The levels of adiponectin in A1 group was lower
      than that of health control group [(6.7 +/- 1.1) versus (10.0 +/- 1.4) ng/L, P <
      0.05], and HOMA-IR was higher than that of health control group (3.5 +/- 1.8
      versus 1.1 +/- 0.7, P < 0.05). While there were not significant difference
      between A2 group and health control group (P > 0.05). Adiponectin and insulin
      resistance was negatively correlated (r = -0.389, P < 0.05). CONCLUSION:
      Adiponectin reducing and insulin resistance in reproductive age patients may be
      the independent factors to promote endometrial cancers.

PMID- 23141291
TI  - [Study on ovary development in vitrification of embryos born mice and expression
      of growth differentiation factor 9].
AB  - OBJECTIVE: To study ovarian development in vitrification of embryos born mice and
      expression of growth differentiation factor 9 (GDF-9) in its. METHODS: The
      vitrification recovery embryos (vitrified-embryo group) and fresh embryos (fresh
      embryo group) were transplanted into pseudopregnant mice, respectively. The
      female offspring mice in two groups were sacrificed on the 3(rd), 7(th), 14(th),
      21(st), 28(th) and 60(th) day after birth, the ovarian tissues were taken, 6 mice
      in each time point of each group. The ovarian development was observed by HE
      staining, the expression of GDF-9 mRNA and protein at each time point of two
      groups were detected by reverse transcription (RT)-PCR and western blot. RESULTS:
      HE staining showed that no abnormal ovarian development was observed in
      offsprings at two groups. On the 3(rd), 7(th), 14(th), 21(st), 28(th) and 60(th)
      day after birth, the expression of GDF-9 mRNA in vitrified-embryo group were 0.14
      +/- 0.07, 0.42 +/- 0.16, 1.00 +/- 0.24, 1.59 +/- 0.28, 2.05 +/- 0.32 and 2.23 +/-
      0.21, respectively, which in fresh-embryo group were 0.13 +/- 0.06, 0.45 +/-
      0.18, 1.00 +/- 0.21, 1.56 +/- 0.26, 2.01 +/- 0.37 and 2.26 +/- 0.23,
      respectively, there was no statistical difference between two groups (P > 0.05);
      the expression of GDF-9 protein in vitrified-embryo group were 0.040 +/- 0.030,
      0.120 +/- 0.060, 0.170 +/- 0.030, 0.250 +/- 0.040, 0.320 +/- 0.060 and 0.330 +/-
      0.010, respectively, which in fresh-embryo group were 0.030 +/- 0.020, 0.110 +/-
      0.040, 0.150 +/- 0.010, 0.210 +/- 0.020, 0.360 +/- 0.070 and 0.350 +/- 0.030,
      respectively, there was no statistical difference between two groups (P > 0.05).
      CONCLUSION: The ovarian morphology in vitrification of embryos born mice and
      expression of GDF-9 in ovary has no any obvious change.

PMID- 23141292
TI  - Defective presynaptic choline transport underlies hereditary motor neuropathy.
AB  - The neuromuscular junction (NMJ) is a specialized synapse with a complex
      molecular architecture that provides for reliable transmission between the nerve
      terminal and muscle fiber. Using linkage analysis and whole-exome sequencing of
      DNA samples from subjects with distal hereditary motor neuropathy type VII, we
      identified a mutation in SLC5A7, which encodes the presynaptic choline
      transporter (CHT), a critical determinant of synaptic acetylcholine synthesis and
      release at the NMJ. This dominantly segregating SLC5A7 mutation truncates the
      encoded product just beyond the final transmembrane domain, eliminating cytosolic
      C-terminus sequences known to regulate surface transporter trafficking. Choline
      transport assays in both transfected cells and monocytes from affected
      individuals revealed significant reductions in hemicholinium-3-sensitive choline
      uptake, a finding consistent with a dominant-negative mode of action. The
      discovery of CHT dysfunction underlying motor neuropathy identifies a biological
      basis for this group of conditions and widens the spectrum of disorders that
      derive from impaired NMJ transmission. Our findings compel consideration of
      mutations in SLC5A7 or its functional partners in relation to unexplained motor
      neuronopathies.

PMID- 23141293
TI  - DHTKD1 mutations cause 2-aminoadipic and 2-oxoadipic aciduria.
AB  - Abnormalities in metabolite profiles are valuable indicators of underlying
      pathologic conditions at the molecular level. However, their interpretation
      relies on detailed knowledge of the pathways, enzymes, and genes involved.
      Identification and characterization of their physiological function are therefore
      crucial for our understanding of human disease: they can provide guidance for
      therapeutic intervention and help us to identify suitable biomarkers for
      monitoring associated disorders. We studied two individuals with 2-aminoadipic
      and 2-oxoadipic aciduria, a metabolic condition that is still unresolved at the
      molecular level. This disorder has been associated with varying neurological
      symptoms. Exome sequencing of a single affected individual revealed compound
      heterozygosity for an initiating methionine mutation (c.1A>G) and a missense
      mutation (c.2185G>A [p.Gly729Arg]) in DHTKD1. This gene codes for dehydrogenase
      E1 and transketolase domain-containing protein 1, which is part of a 2
      oxoglutarate-dehydrogenase-complex-like protein. Sequence analysis of a second
      individual identified the same missense mutation together with a nonsense
      mutation (c.1228C>T [p.Arg410(*)]) in DHTKD1. Increased levels of 2-oxoadipate in
      individual-derived fibroblasts normalized upon lentiviral expression of the wild
      type DHTKD1 mRNA. Moreover, investigation of L-lysine metabolism showed an
      accumulation of deuterium-labeled 2-oxoadipate only in noncomplemented cells,
      demonstrating that DHTKD1 codes for the enzyme mediating the last unresolved step
      in the L-lysine-degradation pathway. All together, our results establish
      mutations in DHTKD1 as a cause of human 2-aminoadipic and 2-oxoadipic aciduria
      via impaired turnover of decarboxylation 2-oxoadipate to glutaryl-CoA.

PMID- 23141294
TI  - A nonsense mutation in DHTKD1 causes Charcot-Marie-Tooth disease type 2 in a
      large Chinese pedigree.
AB  - Charcot-Marie-Tooth (CMT) disease represents a clinically and genetically
      heterogeneous group of inherited neuropathies. Here, we report a five-generation
      family of eight affected individuals with CMT disease type 2, CMT2. Genome-wide
      linkage analysis showed that the disease phenotype is closely linked to
      chromosomal region 10p13-14, which spans 5.41 Mb between D10S585 and D10S1477.
      DNA-sequencing analysis revealed a nonsense mutation, c.1455T>G (p.Tyr485(*)), in
      exon 8 of dehydrogenase E1 and transketolase domain-containing 1 (DHTKD1) in all
      eight affected individuals, but not in other unaffected individuals in this
      family or in 250 unrelated normal persons. DHTKD1 mRNA expression levels in
      peripheral blood of affected persons were observed to be half of those in
      unaffected individuals. In vitro studies have shown that, compared to wild-type
      mRNA and DHTKD1, mutant mRNA and truncated DHTKD1 are significantly decreased by
      rapid mRNA decay in transfected cells. Inhibition of nonsense-mediated mRNA decay
      by UPF1 silencing effectively rescued the decreased levels of mutant mRNA and
      protein. More importantly, DHTKD1 silencing was found to lead to impaired energy
      production, evidenced by decreased ATP, total NAD(+) and NADH, and NADH levels.
      In conclusion, our data demonstrate that the heterozygous nonsense mutation in
      DHTKD1 is one of CMT2-causative genetic alterations, implicating an important
      role for DHTKD1 in mitochondrial energy production and neurological development.

PMID- 23141295
TI  - Tacrolimus as a part of immunosuppressive treatment in kidney transplantation
      patients: sex differences.
AB  - BACKGROUND: Metabolism interaction between corticosteroids and tacrolimus (Tac)
      exists and can be an important factor in providing rational pharmacotherapy in
      kidney transplantation patients. Both Tac and corticosteroids can induce adverse
      metabolic effects, such as hyperglycemia, post-transplantation diabetes mellitus,
      and dyslipidemia. OBJECTIVE: The main goal of this study was to detect
      corticosteroid dose influence on Tac level within the first 6 months of
      immunosuppressive therapy. The secondary goal of this research was to investigate
      sex differences on Tac-corticosteroid interaction. We also monitored biochemical
      parameter changes, which are related to immunosuppressive treatment. METHODS:
      This retrospective pharmacokinetic study included 30 Serbian patients after
      kidney transplantation. Patients received a quaternary immunosuppressive regimen
      including Tac, mycophenolate, mofetil, basiliximab, and corticosteroids. To
      compare dose-normalized level and dose of Tac in different days after
      transplantation, we performed the Friedman test and Wilcoxon matched-pairs signed
      rank sum test. Mann-Whitney test was performed to compare differences in dose of
      Tac, level of Tac, and dose-normalized level of Tac between male and female
      patient groups. We used the Friedman test to compare biological and clinical
      data. RESULTS: Obtained results show statistical significance between dose of Tac
      on day 180 post transplantation and dose on days 7, 14, 21, and 60 post
      transplantation. There was a statistical difference in dose-normalized level of
      Tac between days 7 and 21 post transplantation (P < 0.01), days 7 and 60 (P <
      0.01), and between days 7 and 180 (P < 0.05). There is a statistical significance
      between male and female levels of Tac on day 21 after transplantation (P < 0.01).
      Significance also exists on day 60 after transplantation between male and female
      dose-normalized levels (P < 0.05). There is also a statistical difference in
      glucose, cholesterol, triglyceride, serum creatinine, and urea level and activity
      of alanine aminotransferase and alkaline phosphatase before and after operation.
      CONCLUSION: Our study shows that dose of corticosteroid affects Tac level in
      kidney transplantation patients. Tac dose and level changes showed that
      corticosteroid-Tac interaction has more influence on male than female patients.
      According to biochemical monitoring, the immunosuppressive therapy used at
      present is quite well tolerated.

PMID- 23141296
TI  - Gender differences in questions asked in an online preoperative patient education
      program.
AB  - BACKGROUND: Although osteoarthritis more commonly affects women than men, women
      are 3 times less likely to undergo hip or knee replacement surgery compared with
      men. Disparity in the appropriate utilization of surgery between men and women is
      a complex subject that must take into account the willingness of a patient to
      proceed with the operation. Adequately addressing patient concerns before surgery
      may influence such willingness. OBJECTIVE: We examined if a gender difference can
      be identified in the frequency and types of questions submitted by patients
      scheduled for total hip or total knee arthroplasty. METHODS: Patients completed
      an online interactive preoperative educational program and a database was created
      containing deidentified information on surgical procedure, sex, year of birth,
      and any questions that were submitted. Data were also available regarding the
      total number of patients issued the program, the number of patients who started
      the program, and the number of patients who completed the program. The results
      were analyzed by Wilcoxon rank sum test. P values <=0.05 were considered
      statistically significant. RESULTS: Among the 2770 women and 1708 men included in
      the study, 935 (34%) and 462 (27%) asked at least 1 question, respectively.
      Compared with men, women asked a significantly greater number of questions
      overall (P < 0.001). Women also asked a significantly greater number of questions
      in the categories Your Condition (P = 0.031), Your Procedure (P < 0.001), and
      Risks and Benefits (P < 0.001). CONCLUSIONS: Gender differences in concerns and
      physicians' ability to adequately address these concerns may contribute to
      disparity in use of hip and knee replacement surgery between men and women.
      Effective preoperative counseling for women may require additional resources to
      address their higher level of questions.

PMID- 23141297
TI  - Feline polymorphonuclear neutrophils produce pro-inflammatory cytokines following
      exposure to Microsporum canis.
AB  - The mechanisms involved in the establishment of the specific immune response
      against dermatophytes remain unknown. Polymorphonuclear neutrophils (PMNs) are
      recruited early during the infection process and participate in the elimination
      of dermatophytes. They could therefore be involved in the induction of the immune
      response during dermatophytoses by producing specific cytokines. The aim of this
      work was to assess the in vitro cytokine production by feline PMNs exposed to
      living arthroconidia from the dermatophyte species Microsporum canis or
      stimulated with either a secreted or a structural component of M. canis, the
      latter consisting of heat-killed arthroconidia. The levels of specific cytokines
      produced by PMNs were determined by capture ELISA and/or quantitative RT-PCR.
      Results showed that PMNs secrete TNFalpha, IL-1beta and IL-8 following exposure
      to M. canis living arthroconidia and stimulation with both a secreted component
      and heat-killed arthroconidia. The level of IL-8 mRNA was also increased in PMNs
      stimulated with M. canis living arthroconidia. In conclusion, infective M. canis
      arthroconidia induce the production of pro-inflammatory cytokines by feline PMNs
      that can be activated either by secreted or structural fungal components. Our
      results suggest that these granulocytes are involved in the initiation of the
      immune response against M. canis.

PMID- 23141298
TI  - Vaccination against seasonal flu in Switzerland: The indecision of pregnant women
      encouraged by healthcare professionals.
AB  - BACKGROUND: The recommendation for seasonal flu immunization from the second
      trimester of pregnancy, adopted in summer 2010 in Switzerland, is situated within
      a social context characterized by reluctance toward some vaccinations, a
      relatively low vaccination coverage against flu in the general population, and
      still heated debates fuelled by vaccination campaigns organized around the
      A(H1N1)pdm09 flu pandemic in winter 2009 to 2010. This study examines Swiss
      pregnant women's representations of the risks associated with seasonal flu and
      its vaccination. METHODS: Semi-structured interviews were conducted with 29
      women, while in the maternity unit in March 2011, 3 to 5 days after giving birth.
      The interviews addressed the risks associated with flu, modes of protection,
      motivations for, and obstacles to vaccination. RESULTS: The interviewees did not
      show major preoccupations regarding seasonal flu and they tended to distance
      themselves from the at-risk status. They did not directly challenge seasonal flu
      immunization; however, they were reluctant to do it. Their attitudes were
      supported by their personal experience and the experience of their social
      networks. Healthcare professionals, particularly medical doctors, gave very
      little direction, or even did not raise the issue with them. CONCLUSIONS: Between
      the rather moderate positions of those who are against vaccination and those who
      support it, an intermediate grey zone, characterized by hesitation, was observed.
      Furthermore, the indecision of pregnant women is reinforced by doubts among the
      persons they are close to and also among the professionals they met during their
      pregnancy.

PMID- 23141299
TI  - EMS triage and transport of intoxicated individuals to a detoxification facility
      instead of an emergency department.
AB  - STUDY OBJECTIVE: We evaluate the effectiveness and safety of emergency medical
      services (EMS) provider use of a checklist to triage alcohol-inebriated patients
      directly to a detoxification facility, rather than an emergency department (ED).
      METHODS: A retrospective cohort study was conducted of all patients evaluated
      during a 2-year period, from 2003 to 2005, by EMS providers who used a
      detoxification evaluation checklist to aid in triage decisionmaking. Patients who
      did not meet detoxification evaluation checklist criteria were transported to an
      ED. Twelve-hour follow-up was solicited for patients taken to the detoxification
      center. Hospital records of inebriated patients transported to an ED were
      reviewed to assess ultimate need for ED care. RESULTS: Seven hundred eighteen
      patient encounters were reviewed. One hundred thirty-eight of these patients
      (19.2%) were transported to the detoxification facility, whereas 580 (80.8%) were
      transported to an ED; 339 patients transported to an ED were ultimately deemed to
      have required ED care. The criteria that most commonly excluded transport to the
      detoxification center were an inability to ambulate with minimal assistance
      (N=334) and an unwillingness to cooperate with the physical examination (N=195).
      Low-acuity adverse events were observed in 4 subjects (0.6%) initially
      transported to the detoxification center who then required subsequent transport
      to an ED. No high-acuity clinical complications were identified at any time. The
      use of the detoxification evaluation checklist resulted in high sensitivity (99%;
      95% confidence interval 97% to 100%) and low specificity (42%; 95% confidence
      interval 37% to 48%) in predicting need for ED care. CONCLUSION: Our analysis
      suggests that field triage criteria can be used effectively to safely divert
      inebriated patients to a detoxification facility rather than an ED, with minimal
      adverse events. Use of the detoxification evaluation checklist resulted in
      substantial ED overtriage, and further refinement of the detoxification
      evaluation checklist criteria is needed to reduce it.

PMID- 23141300
TI  - Multislice computed tomography for the study of complications of gastric
      fundoplication.
AB  - The traditional approach to the imaging evaluation of patients after gastric
      fundoplication is an upper gastrointestinal series obtained by fluoroscopy. In
      this article, we describe a new technique using multislice computed tomography
      that we think can be useful to evaluate patients with suspected complications or
      late failure after gastric fundoplication.

PMID- 23141301
TI  - On the trail of empty MHC class-I.
AB  - Since being proposed nearly 25 years ago that MHC-I molecules free of peptide
      ligand possess a conformation that is distinct from that of the mature loaded
      form, considerable research has been conducted in order to isolate and
      characterise such a species. While some progress has been made in our
      understanding, many questions still surround the nature and loading of empty MHC
      I. However, the necessary tools to address these questions may finally be at
      hand.

PMID- 23141303
TI  - A fast and sensitive immunoassay of avian influenza virus based on label-free
      quantum dot probe and lateral flow test strip.
AB  - A novel fluorescence immunoassay method for fast and ultrasensitive detection of
      avian influenza virus (AIV) was developed. The immunoassay method which
      integrated lateral flow test strip technique with fluorescence immunoassay used
      the label-free and high luminescent quantum dots (QDs) as signal output. By the
      sandwich immunoreaction performed on lateral flow test strip, the gold
      nanoparticle (NP) labels were captured in the test zone and further dissolved to
      release a large number of gold ions as a signal transduction bridge that was
      detected by the QDs-based fluorescence quenching method. Under the optimal
      conditions, the relative fluorescence intensity of QDs was linear over the range
      of 0.27-12 ng mL(-1) AIV, and the limit of detection was estimated to be 0.09 ng
      mL(-1) which was 100-fold greater than enzyme-linked immunosorbent assay (ELISA).
      The sensitive and specific response was also coupled with high reproducibility in
      the proposed method. A series of six parallel measurements produced reproducible
      fluorescent signals with a relative standard deviation of 4.7%. The proposed
      method can be used to directly detect clinical sample without any pretreatment,
      and showed high efficiency (90.0%), sensitivity (100.0%) and specificity (88.2%)
      compared with virus isolation (gold method). The new method shows great promise
      for rapid, sensitive, and quantitative detection of AIV in-field or point-of-care
      diagnosis.

PMID- 23141305
TI  - Accurate approach for determining fresh-water carbonate (H2CO3(*)) alkalinity,
      using a single H3PO4 titration point.
AB  - A new, simple and accurate method is introduced for determining H(2)CO(3)(*)
      alkalinity in fresh waters dominated by the carbonate weak-acid system. The
      method relies on a single H(3)PO(4) dosage and two pH readings (acidic pH value
      target: pH~4.0). The computation algorithm is based on the concept that the
      overall alkalinity mass of a solution does not change upon the addition of a non
      proton-accepting species. The accuracy of the new method was assessed batch-wise
      with both synthetic and actual tap waters and the results were compared to those
      obtained from two widely used alkalinity analysis methods (titration to pH~4.5
      and the Gran titration method). The experimental results, which were deliberately
      obtained with simple laboratory equipment (glass buret, general-purpose pH
      electrode, magnetic stirrer) proved the method to be as accurate as the
      conventional methods at a wide range of alkalinity values (20-400 mg L(-1) as
      CaCO(3)). Analysis of the relative error attained in the proposed method as a
      function of the target (acidic) pH showed that at the range 4.0<pH<4.5 the error
      was minimal. A suggested experimental setup for continuous alkalinity measurement
      is also described.

PMID- 23141302
TI  - Neutrophil rolling at high shear: flattening, catch bond behavior, tethers and
      slings.
AB  - Neutrophil recruitment to sites of inflammation involves neutrophil rolling along
      the inflamed endothelium in the presence of shear stress imposed by blood flow.
      Neutrophil rolling in post-capillary venules in vivo is primarily mediated by P
      selectin on the endothelium binding to P-selectin glycoprotein ligand-1 (PSGL-1)
      constitutively expressed on neutrophils. Blood flow exerts a hydrodynamic drag on
      the rolling neutrophil which is partially or fully balanced by the adhesive
      forces generated in the P-selectin-PSGL-1 bonds. Rolling is the result of rapid
      formation and dissociation of P-selectin-PSGL-1 bonds at the center and rear of
      the rolling cell, respectively. Neutrophils roll stably on P-selectin in post
      capillary venules in vivo and flow chambers in vitro at wall shear stresses
      greater than 6 dyn cm(-2). However, the mechanisms that enable neutrophils to
      roll at such high shear stress are not completely understood. In vitro and in
      vivo studies have led to the discovery of four potential mechanisms, viz. cell
      flattening, catch bond behavior, membrane tethers, and slings. Rolling
      neutrophils undergo flattening at high shear stress, which not only increases the
      size of the cell footprint but also reduces the hydrodynamic drag experienced by
      the rolling cell. P-selectin-PSGL-1 bonds behave as catch bonds at small
      detachment forces and thus become stronger with increasing force. Neutrophils
      rolling at high shear stress form membrane tethers which can be longer than the
      cell diameter and promote the survival of P-selectin-PSGL-1 bonds. Finally,
      neutrophils rolling at high shear stress form 'slings', which act as cell
      autonomous adhesive substrates and support step-wise peeling. Tethers and slings
      act together and contribute to the forces balancing the hydrodynamic drag. How
      the synergy between the four mechanisms leads to stable rolling at high shear
      stress is an area that needs further investigation.

PMID- 23141304
TI  - Enzymatic analysis of alpha-ketoglutaramate--a biomarker for hyperammonemia.
AB  - Two enzymatic assays were developed for the analysis of alpha-ketoglutaramate
      (KGM)-an important biomarker of hepatic encephalopathy and other hyperammonemic
      diseases. In both procedures, KGM is first converted to alpha-ketoglutarate (KTG)
      via a reaction catalyzed by omega-amidase (AMD). In the first procedure, KTG
      generated in the AMD reaction initiates a biocatalytic cascade in which the
      concerted action of alanine transaminase and lactate dehydrogenase results in the
      oxidation of NADH. In the second procedure, KTG generated from KGM is reductively
      aminated, with the concomitant oxidation of NADH, in a reaction catalyzed by L
      glutamic dehydrogenase. In both assays, the decrease in optical absorbance
      (lambda=340 nm) corresponding to NADH oxidation is used to quantify
      concentrations of KGM. The two analytical procedures were applied to 50% (v/v)
      human serum diluted with aqueous solutions containing the assay components and
      spiked with concentrations of KGM estimated to be present in normal human plasma
      and in plasma from hyperammonemic patients. Since KTG is the product of AMD
      catalyzed hydrolysis of KGM, in a separate study, this compound was used as a
      surrogate for KGM. Statistical analyses of samples mimicking the concentration of
      KGM assumed to be present in normal and pathological concentration ranges were
      performed. Both enzymatic assays for KGM were confirmed to discriminate between
      the predicted normal and pathophysiological concentrations of the analyte. The
      present study is the first step toward the development of a clinically useful
      probe for KGM analysis in biological fluids.

PMID- 23141306
TI  - Determination of lead in medicinal plants by high-resolution continuum source
      graphite furnace atomic absorption spectrometry using direct solid sampling.
AB  - A procedure is proposed for Pb determination in medicinal plants by high
      resolution continuum source graphite furnace atomic absorption spectrometry (HR
      CS GF AAS) using direct solid sampling. Among Pd(NO(3))(2), Pd/Mg(NO(3))(2),
      NH(4)H(2)PO(4) and the W-coated platform tested as chemical modifiers,
      Pd(NO(3))(2) presented the best performance. Calibration plots (10-1000 pg Pb)
      with regression coefficients better than 0.999 were typically obtained. Accuracy
      was checked for Pb determination in five plant certified reference materials.
      Results were in agreement with reference values at a 95% confidence level (paired
      t-test). Medicinal plant samples were analyzed by the proposed procedure and line
      source GF AAS using slurry sampling as a comparative technique. The RSD was 10%
      (n=3) for a sample containing 0.88 MUg g(-1) Pb. The limit of quantification (dry
      mass) was 0.024 MUg g(-1). The contents of Pb in medicinal plant samples varied
      in the 0.30-1.94 MUg g(-1) range.

PMID- 23141307
TI  - Signal-to-noise ratio enhancement of the compact light-emitting diode-induced
      fluorescence detector.
AB  - To enhance the SNR (signal-to-noise ratio) of the compact light-emitting diode
      induced fluorescence detector (LED-FD) ([14]), key parameters including LED and
      its coupling style, pinhole diameter, calibration, and refractive index matching
      fluid (RIMF) were optimized. A 20 mA LED with light intensity of 8400 mcd was
      used as new light source. To optimize pinhole diameter, a theoretical analysis
      based on a three-dimensional (3D) view of the detection area was proposed and
      validated experimentally. A calibration principle from the 3D perspective was
      proposed. The detection flow cell and the collection fiber were adjusted to be
      coplanar. RIMF (glycerol) was applied to enhance SNR. The performance of the
      improved LED-FD was evaluated by flow injection analysis (FIA). The limit of
      detection (LOD) was determined as 0.15 nM sodium fluorescein (SNR=3). Compared
      with our previous work, a five-fold enhancement on the SNR was obtained. The LOD
      was about five times higher than that of commercial Agilent G1321A FLD which
      employed a xenon pulse lamp.

PMID- 23141308
TI  - A novel surface-enhanced Raman scattering sensor to detect prohibited colorants
      in food by graphene/silver nanocomposite.
AB  - A novel surface-enhanced Raman scattering (SERS) sensor made up of a graphene and
      silver nanocomposite was developed for detecting prohibited colorants in food.
      This SERS platform exhibited an excellent enrichment effect between the colorant
      molecules and the graphene and an ability to enhance the Raman spectra of the
      silver nanoparticles. Detection of different concentrations of each prohibited
      colorant was carried out by SERS measurements on this novel substrate. In
      addition, from the SERS spectra of a mixture of four kinds of prohibited
      colorants, it was possible to easily distinguish each colorant by its
      characteristic peaks. A control experiment was also performed to compare the SERS
      spectra obtained using the graphene/silver nanocomposite substrate with spectra
      obtained using Ag alone as a substrate. The results showed that the SERS
      nanocomposite was better for detecting prohibited colorants. The proposed method
      has advantages in terms of providing a simple and rapid method for the sensitive
      analysis of prohibited additive colorants in food.

PMID- 23141309
TI  - Determination of some organic contaminants in water samples by solid-phase
      extraction and liquid chromatography-tandem mass spectrometry.
AB  - Independent methods for determination of organic contaminants such as
      pharmaceuticals and pesticides in drinking water samples, using SPE as the
      extraction technique and LC-MS/MS in the MRM mode with electrospray ionization,
      were developed and validated. Different SPE sorbents were evaluated, including
      lab-made fluorinated and phenyl and commercial Oasis HLB and C18, with the
      commercial phases being more suitable for the target compounds. Recoveries in the
      range of 70-120% were obtained for all target compounds, with the exception for
      paracetamol (acetaminophen), and precision values (inter-day and intra-day),
      expressed in terms of relative standard deviations (RSD), lower than 20% were
      obtained for all target compounds. Quantification limits were in the range of
      0.006-0.208 MUg L(-1) and the methods developed were successfully applied for the
      analysis of drinking water samples, detecting some pharmaceuticals and
      pesticides, but at concentration levels lower than the MRL.

PMID- 23141310
TI  - Analytical performance of a lab-made concomitant metal analyzer to generate
      volatile species of Ag, Au, Cd, Cu, Ni, Sn and Zn using 8-hydroxyquinoline as a
      reaction media.
AB  - This study evaluated the main parameters affecting Ag, Au, Cd, Cu, Ni, Sn and Zn
      vapor generation using a lab-made concomitant metal analyzer (CMA) as a reaction
      chamber and gas-liquid separator. The modifier used in the reaction media was 8
      hydroxyquinoline, and Inductively-Coupled Plasma Optical Emission Spectrometry
      was used as detection technique. The performance of the lab-made concomitant
      analyzer was compared with the performance of a continuous flow gas-liquid
      separator and of a cyclonic spray chamber. Standards were prepared in acid media
      and included 1 mg L(-1) of Co as a catalyzer. The optimum concentrations of the
      reagents in the standards were: 450 mg L(-1) of 8-hydroxyquinoline and 0.4 M
      nitric acid. The optimum concentration of sodium borohydride to generate the
      vapors was 2.25% (w/v) (prepared in 0.4% (w/v) NaOH). The volatile species were
      swept from the CMA to the torch by an argon flow of 0.6 mL min(-1). The use of
      the CMA led to an improvement of the detection limits for some elements compared
      to conventional nebulization: 1.1 MUg L(-1) for Ag, 7.0 MUg L(-1) for Au and 4.3
      MUg L(-1) for Sn. The limit of detection for Cu was 1.4 MUg L(-1) and for Ni 22.5
      MUg L(-1). The direct mixing of the reagents on the spray chamber was not
      effective for Cd and Zn; a deviation of the linearity was observed for these
      elements.

PMID- 23141311
TI  - A metabonomic approach to the effect evaluation of treatment in patients infected
      with influenza A (H1N1).
AB  - The pandemic influenza A virus (H1N1) was transmitted to the human population
      since 2009, resulting in some consequences of viral pneumonia, respiratory
      failure, multiple organ failure and, most severely, death. In clinical practice,
      Chinese medicine possessed extensive experience for prevention and treatment of
      influenza, but its mechanism still remain unclear. In addition, the efficacy of
      combination therapy of Chinese and Western medicine was attractive, but not yet
      clear. In the present study, 131 patients from Guangzhou China referred for H1N1
      virus mRNA testing for the evaluation of possible influenza A-infected were
      eligible for participation. A metabonomics study was carried out to explore the
      difference between before and after treatment in patients with H1N1 through
      Chinese and/or Western medicine. Results from metabolic profiling and biochemical
      detection indicated significant metabolic change in the arachidonic acid
      metabolic pathway. In the group of combination therapy of Chinese and western
      medicine, its efficacy was best and the potential biomarkers were significantly
      changed compared with untreated state. Those results indicated that the potential
      metabolic biomarker could be supplemented with biochemical detection to obtain
      more precise diagnosis for H1N1 infection. CLINICAL TRIALS REGISTRATION: Clinical
      Trials. Gov No. 2008GL-50.

PMID- 23141312
TI  - Complexation of Hg(II) by humic acid studied by square wave stripping voltammetry
      at screen-printed gold electrodes.
AB  - This paper reports the development of a sequential injection (SI) method to study
      the complexation of Hg(II) by humic acid (HA) using square wave anodic stripping
      voltammetry at a screen-printed gold electrode (SPGE). The SI system injected
      samples (in 0.020 mol L(-1) NaNO(3) and pH 6.0) to the flow cell during the
      deposition step and exchanged the medium to 0.050 mol L(-1) HCl to perform the
      stripping step under stopped flow conditions. For sample volume=750 MUL, flow
      rate=15 MUL s(-1) (deposition step), and square wave frequency=100 Hz, the
      detection limit was 20 nmol L(-1) and the sampling throughput was 17 analyses per
      hour. Complexation of Hg(II) was studied using a 25.0 mg L(-1) suspension of HA
      (72.5 MUmol L(-1) of ionizable sites), and total Hg(II) concentrations from 1 to
      20 MUmol L(-1). The diffusion coefficient of the complex was (1.3+/-0.2)*10(-7)
      cm(2) s(-1). A complexing capacity of 537 MUmol g(-1) was found. The log of the
      differential stability constant (logK(DEF)) decreased from 7.0 to 5.3 as the log
      of the degree of site occupation (logtheta) increased from -1.6 to -0.5. The
      values of logK(DEF) were consistent with complexation of Hg(II) by carboxylic and
      phenolic groups.

PMID- 23141313
TI  - Vortex solvent bar microextraction for phthalate esters from aqueous matrices.
AB  - An improved hollow fiber solvent bar microextraction method termed as vortex
      solvent bar microextraction (VSBME) was developed. A short hollow fiber
      immobilized with organic extraction solvent was served as the solvent bar for
      microextraction of phthalate esters from aqueous matrices. The hydrophobic
      analytes were pre-focused at the bottom of the vortex under the vigorous magnetic
      stirring before extraction, which facilitated the mass transfer of analytes from
      aqueous matrix to organic extraction phase in the subsequent solvent bar
      microextraction. With the extraction solvent lost gradually from the hollow fiber
      under the stirring, the efficient extraction was maintained by the absorption of
      analytes in the porous membrane. After extraction, the analytes were desorbed
      from the hollow fiber membrane using 50 MUL organic solvent. The phthalate esters
      with 1-octanol/water partition coefficients ranging from 1.69 to 8.83 were used
      as model compounds to investigate the extraction performance. Extraction
      conditions such as type and volume of extraction solvents, stirring intensity,
      extraction time, sample concentration and volume were investigated and optimized.
      Analysis was carried out with gas chromatography-mass spectrometry (GC-MS). Under
      the optimum conditions, this new method gave super high enrichment factors (over
      1500), good reproducibility (<7.1%, n=6) in a rapid extraction within 5 min. It
      allowed the determination of phthalate esters at ng L(-1) level. Compared with
      the other microextraction methods, the proposed VSBME was simpler, more robust
      and had higher enrichment efficiency. The matrix effects on the extraction
      performance were also investigated with bottled ice red tea, red wine and human
      urine.

PMID- 23141314
TI  - Novel on-line sequential preconcentration system of Cr(III) and Cr(VI) hyphenated
      with flame atomic absorption spectrometry exploiting sorbents based on chemically
      modified silica.
AB  - In the present study, a flow injection system using dual mini-columns,
      SiO(2)/Al(2)O(3)/TiO(2) and silica gel functionalized with [3-(2
      aminoethylamino)propyl] trimethoxysilane (SiO(2)/AAPTMS) for the sequential
      preconcentration of Cr(III) and Cr(VI), respectively, from water samples with
      FAAS detection was proposed. A two-level full factorial design (2(4)) and
      desirability function were employed for the optimization of variables related to
      the system performance. The detection limits of 0.66 and 0.27 MUg L(-1) for
      Cr(III) and Cr(IV), respectively, were obtained under the optimized
      preconcentration conditions (flow rate of 7.0 mL min(-1)), pH 5.0, buffer
      concentration (acetate buffer) of 0.01 mol L(-1), and eluent (2.5 mol L(-1) HCl)
      flow rate of 5.0 mL min(-1). The other parameters including preconcentration
      factor (PF), consumptive index (CI), and concentration efficiency (CE) were found
      to be 17.62/32.98, 1.13/0.6 mL, and 6.2/11.54 min(-1) for Cr(III)/Cr(VI),
      respectively. The developed method was applied to the Cr(III) and Cr(VI)
      determination in water samples [tap, lake and mineral water, artificial saliva
      and parenteral solutions (physiological serum, water for injection, and glucose
      physiological solution)]. The method accuracy was checked by the analysis of
      standard reference materials (trace elements in water).

PMID- 23141315
TI  - Fast ultrahigh performance liquid chromatographic method for the simultaneous
      determination of 25 emerging contaminants in surface water and wastewater samples
      using superficially porous sub-3 MUm particles as an alternative to fully porous
      sub-2 MUm particles.
AB  - The development of fused-core silica stationary phases was considered a
      breakthrough in column manufacturing. In this study, a fast LC-UV method was
      developed and validated for the simultaneous determination of 25 emerging
      contaminants in surface water and wastewater. The selected analytes belonged to
      various classes such as veterinary antibiotics, central nervous system
      stimulants, non-steroidal anti-inflammatory drugs, steroids and preservatives.
      The chromatographic separation was optimized in order to achieve suitable
      retention times and good resolution for all analytes in a single run using
      solvent gradient and flow rate gradient. All analytes eluted within 10 min on a
      Kinetex((r)) C18 column packed with fused core particles. Sample preparation was
      executed with solid-phase extraction on Oasis HLB cartridges. The method was
      validated by assessing linearity, selectivity, accuracy, precision, limits of
      detection and limits of quantification. Good recoveries were obtained for all
      analytes ranging from 67.5% to 97.0% with standard deviations not higher than
      5.7%, except for acetaminophen, sulphanilamide and acetyl salicylic acid, for
      which lower recoveries were obtained. The detection limits ranged from 1.5 to 15
      MUg L(-1), while limits of quantification were in the range from 5 to 50 MUg L(
      1). The short analysis time achieved by this method allowed analysis of a large
      number of samples in a short time, minimizing organic solvent consumption and
      lowering LC solvents cost. This fast method offers benefits both environmentally
      and economically.

PMID- 23141316
TI  - Analysis of synthetic endocrine-disrupting chemicals in food: a review.
AB  - This work focuses on a revision of analytical methodologies for the determination
      of industrial chemicals that have an endocrine-disrupting effect on food
      commodities. These food commodities have been divided into two major categories:
      crops and food of animal origin. The reviewed methods have been commented on in
      terms of sample preparation, analytical methods, and the occurrence of the
      studied compounds.

PMID- 23141317
TI  - Isolation/separation of plasmid DNA using hemoglobin modified magnetic
      nanocomposites as solid-phase adsorbent.
AB  - Hemoglobin (Hb) modified magnetic nanocomposites are prepared by immobilization
      of Hb onto the surface of amino-functionalized Fe(3)O(4)@SiO(2) magnetic
      nanoparticles via covalent bonding with glutaraldehyde as cross-linker. The
      obtained nanocomposites are characterized with FT-IR, SEM, XRD and surface charge
      analysis. A direct solid-phase extraction procedure for the isolation/separation
      of plasmid DNA using this nanocomposite as a novel adsorbent is thus developed.
      Some important experimental parameters governing the sorption efficiency, i.e.,
      the pH of sample solution and the ionic strength, are investigated. The Hb
      modified magnetic nanocomposites provide a sorption capacity of 27.86 mg g(-1)
      for DNA. By using 2.0mg of the nanocomposites as sorption medium and a suitable
      acidity of pH 6.1, a sorption efficiency of 93% is achieved for 25 MUg mL(-1) of
      DNA in 1.0 mL of sample solution. Afterwards, the absorbed DNA could be readily
      recovered by using 1.0 mL of Tris-HCl buffer (pH 8.9, 0.01 mol L(-1)), giving
      rise to a recovery of ca. 68.3%. The present solid-phased extraction protocol is
      applied for the isolation of plasmid DNA from Escherichia coli culture, resulting
      in comparable yield and purity of plasmid DNA with respect to those obtained by
      using commercial kits.

PMID- 23141318
TI  - Impurity profiling of capreomycin using dual liquid chromatography coupled to
      mass spectrometry.
AB  - The characterization of unknown (UNK) impurities in capreomycin (CMN) using
      liquid chromatography coupled to mass spectrometry (LC/MS) has been described.
      The ion-pair liquid chromatography method coupled to ultraviolet detection (LC
      UV) described by Mallampati et al. was used for the separation of CMN from its
      related substances. As the method uses non-volatile reagents it could not be
      directly coupled to mass spectrometry (MS) for impurity characterization. So,
      these UNK impurities were collected and desalted before sending to MS for
      structural characterization. As no information about the fragmentation of the
      main components of CMN, except for CMN IB, was available in the literature, they
      were studied first. Next, the structures of the impurities were deduced by
      comparing their fragmentation to that of the main components of CMN. Fourteen UNK
      impurities that were never described before, were (partly) characterized.

PMID- 23141319
TI  - Chemometrics and chromatographic fingerprints to discriminate and classify
      counterfeit medicines containing PDE-5 inhibitors.
AB  - Chromatographic fingerprints recorded for a set of genuine and counterfeit
      samples of Viagra((r)) and Cialis((r)) were evaluated for their use in the
      detection and classification of counterfeit samples of these groups of medicines.
      Therefore several exploratory chemometric techniques were applied to reveal
      structures in the data sets as well as differences among the samples. The focus
      was on the differentiation between genuine and counterfeit samples and on the
      differences between the samples of the different classes of counterfeits as
      defined by the Dutch National Institute for Public Health and the Environment
      (RIVM). In a second part the revealed differences between the samples were
      modelled to obtain a predictive model for both the differentiation between
      genuine and counterfeit samples as well as the classification of the counterfeit
      samples. The exploratory analysis clearly revealed differences in the data for
      the genuine and the counterfeit samples and with projection pursuit and
      hierarchical clustering differences among the different groups of counterfeits
      could be revealed, especially for the Viagra((r)) data set. For both data sets
      predictive models were obtained with 100% correct classification rates for the
      differentiation between genuine and counterfeit medicines and high correct
      classification rates for the classification in the different classes of
      counterfeit medicines. For both data sets the best performing models were
      obtained with Least Square-Support Vector Machines (LS-SVM) and Soft Independent
      Modelling by Class Analogy (SIMCA).

PMID- 23141320
TI  - A straightforward wet-chemistry method for the determination of solid and gaseous
      mercury fractions in Backlight Cold Cathode Fluorescence Lamps.
AB  - Backlight Cold Cathode Fluorescence Lamps (B-CCFLs) are already applied in many
      electronic consumer products such as LCD screens, flat screen TVs, and laptop
      monitors. In consequence, an increase of such products entering the waste streams
      can be expected in the near future. As a result of the mercury (Hg) employed in
      such lamps, the development of recycling techniques to create a best practical
      environmental option for appropriate end-of-life strategies are necessary. For
      this purpose the knowledge about speciation in terms of solid and gaseous state
      of Hg in such lamps is inevitable. However, analytical techniques to discriminate
      solid and gaseous Hg require a special setup, not available in most routine
      laboratories. Thus a straightforward and cost efficient analytical technique is
      of need. In this work we describe sample preparation procedures and analysis
      techniques, which only require equipment already available in most routine
      laboratories. The volatile fraction is extracted with a KMnO(4) solution
      utilizing a novel approach, taking the advantage that the B-CCFL glass tubes have
      a negative pressure. Thus the extraction solution is directly sucked into the
      tube where the volatile Hg-fraction is immediately extracted. Subsequently, the
      solid fraction is dissolved via microwave assisted pressure acid digestion after
      cryo-milling. Analysis for both fractions took place employing a cold vapor
      atomic absorption system. To prove the new method is fit for purpose, spiking
      experiments and analysis of reference materials (when available) was performed
      with recoveries being between 90% and 110%. First results obtained for a stack of
      lamps from an used LCD-TV display reveal that solid Hg fractions in all lamps
      show a variation of 20% between samples whereas the gaseous Hg content can vary
      up to 600%.

PMID- 23141321
TI  - A thin layer-based amperometric enzyme immunoassay for the rapid and sensitive
      diagnosis of respiratory syncytial virus infections.
AB  - A simple electrochemical sandwich immunoassay involving a polystyrene microarray
      slide coated with monoclonal capture antibodies and carbon screen-printed sensors
      (SPS) was designed for the rapid diagnosis of respiratory syncytial virus (RSV).
      The detection of the antibody-antigen complex formation relied on the use of a
      horseradish peroxidase conjugate. Its chronoamperometric measurement detection
      was performed by confining a droplet of H(2)O(2)/3,3',5,5'-tetramethylbenzidine
      enzyme substrate/mediator solution within a thin layer between one spot of the
      microarray and the surface of one screen-printed electrochemical cell. The
      accumulation of the enzyme product in the thin film of liquid enhanced the
      electrochemical response which allowed the development of a rapid (25 min) and
      sensitive thin layer-based amperometric (TLA) enzyme immunoassay. The method was
      successfully compared to commercially-available immunofluorescent and real-time
      PCR assays for RSV testing in respiratory secretion clinical samples. This
      suggests that owing to its rapidity, convenience, low-cost, portability and
      ability to provide quantified results, the reported concept could be a promising
      point-of-care diagnostic tool to screen patients with suspected respiratory
      infection or other types of infectious diseases.

PMID- 23141322
TI  - Comparison between sampling and analytical methods in characterization of
      pollutants in biogas.
AB  - Different sampling methods involving the collection of biogas by Tedlar bags or
      adsorption tubes, and different GC-MS injection systems, loop injection or cold
      trap injection (with bags or by tube desorption), were compared to establish the
      best method to determine the minority compounds in biogas from sewage treatment
      plants (STPs). A study of parameters is included, such as the stability of
      compounds in Tedlar bags or cartridges and the adsorption effect of some less
      volatile compounds in the thermal desorption system (TD). The optimized methods
      allowed to determine most compounds at low mgm(-3) levels. Among them, maximum
      values of D5 (4.84 mg m(-3)), decane (95-118 mg m(-3)) and H(2)S (2223 mg m(-3))
      were found in biogas samples.

PMID- 23141323
TI  - A novel extraction technique based on carbon nanotubes reinforced hollow fiber
      solid/liquid microextraction for the measurement of piroxicam and diclofenac
      combined with high performance liquid chromatography.
AB  - A novel design of carbon nanotubes reinforced hollow fiber solid/liquid phase
      microextraction (CNTs-HF-SLPME) was developed to determine piroxicam and
      diclofenac in different real water samples. Functionalized multi-walled carbon
      nanotubes (MWCNTs) were held in the pores of hollow fiber with sol-gel
      technology. The pores and lumen of carbon nanotubes reinforced hollow fiber were
      subsequently filled with a MUL volume of organic solvent (1-octanol), and then
      the whole assembly was used for the extraction of the target analytes in direct
      immersion sampling mode. The target analytes were extracted from the sample by
      two extractants, one of which is organic solvent placed inside the pores and
      lumen of hollow fiber and the other one is CNTs held in the pores of hollow
      fiber. After extraction, the analytes were desorbed in acetonitrile and analyzed
      using high performance liquid chromatography. This novel extraction mode showed
      more excellent extraction performance in comparison with conventional hollow
      fiber liquid microextraction (without adding CNTs) and carbon nanotubes
      reinforced hollow fiber solid microextraction (CNTs held in the pores of hollow
      fiber, but no organic solvents placed inside the lumen of hollow fiber) under the
      respective optimum conditions. This method provided 47- and 184-fold enrichment
      factors for piroxicam and diclofenac, respectively, good inter-fiber
      repeatability and batch-to-batch reproducibility. Linearity was observed in the
      range of 20-960 MUg L(-1) for piroxicam, and 10-2560 MUg L(-1) for diclofenac,
      with correlation coefficients of 0.9985 and 0.9989, respectively. The limits of
      detection were 4.58 MUg L(-1) for piroxicam and 0.40 MUg L(-1) for diclofenac.

PMID- 23141324
TI  - Reagent-less electrogenerated chemiluminescence peptide-based biosensor for the
      determination of prostate-specific antigen.
AB  - A novel electrogenerated chemiluminescence peptide-based (ECL-PB) biosensor for
      highly sensitive and selective determination of prostate-specific antigen (PSA)
      was developed. A helix peptide (CHSSKLQK) was served as a molecular recognition
      element and ruthenium bis(2,2'-bipyridine) (2,2'-bipyridine-4,4'-dicarboxylic
      acid)-N-hydroxysuccinimide ester (Ru(bpy)(2)(dcbpy)NHS) was used as an ECL label.
      The helix peptide was labeled with the ECL label at NH(2)-containing lysine and
      utilized as ECL probe (Ru-peptide). The ECL-PB biosensor was fabricated by
      immobilizing the ECL probe onto a gold electrode surface via self-assembling
      technique through a thiol-containing cysteine at the end of the peptide. The
      principle of ECL measurement is based on the specific proteolytic cleavage event
      of Ru-peptide on the gold electrode surface in the presence of PSA, resulting in
      a decrease of ECL signal. The decreased ECL intensity was directly linear to the
      concentration of PSA in the range from 1.0*10(-10) g/mL to 8.0*10(-9) g/mL with a
      detection limit of 3.8*10(-11) g/mL. This work demonstrates that the direct
      transduction of peptide cleavage events into an ECL signal provides a simple and
      sensitive method for detecting target protein.

PMID- 23141325
TI  - Virtual electrochemical nitric oxide analyzer using copper, zinc superoxide
      dismutase immobilized on carbon nanotubes in polypyrrole matrix.
AB  - In this work, we have designed and developed a novel and cost effective virtual
      electrochemical analyzer for the measurement of NO in exhaled breath and from
      hydrogen peroxide stimulated endothelial cells using home-made potentiostat.
      Here, data acquisition system (NI MyDAQ) was used to acquire the data from the
      electrochemical oxidation of NO mediated by copper, zinc superoxide dismutase
      (Cu,ZnSOD). The electrochemical control programs (graphical user-interface
      software) were developed using LabVIEW 10.0 to sweep the potential, acquire the
      current response and process the acquired current signal. The Cu,ZnSOD (SOD1)
      immobilized on the carbon nanotubes in polypyrrole modified platinum electrode
      was used as the NO biosensor. The electrochemical behavior of the SOD1 modified
      electrode exhibited the characteristic quasi-reversible redox peak at the
      potential, +0.06 V vs. Ag/AgCl. The biological interferences were eliminated by
      nafion coated SOD1 electrode and then NO was measured selectively. Further, this
      biosensor showed a wide linear range of response over the concentration of NO
      from 0.1 MUM to 1 mM with a detection limit of 0.1 MUM and high sensitivity of
      1.1 MUA MUM(-1). The electroanalytical results obtained here using the developed
      virtual electrochemical instrument were also compared with the standard cyclic
      voltammetry instrument and found in agreement with each other.

PMID- 23141326
TI  - Reliable quantification of bisphenol A and its chlorinated derivatives in human
      breast milk using UPLC-MS/MS method.
AB  - Bisphenol A is a widespread industrial chemical which over the past decade has
      demonstrated its toxicity as an endocrine disruptor. Chlorine present in drinking
      water may react with bisphenol A to form chlorinated derivatives, which have
      demonstrated a heightened level of estrogenic activity. In this work, we have
      comprehensively validated a method using on-line SPE-UPLC-MS/MS and isotope
      dilution quantification to measure bisphenol A and its chlorinated derivatives in
      human breast milk according to accepted guidelines. Deutered bisphenol A was used
      as internal standard. The matrix calibration curve ranged from 0.40 to 6.40 ng/mL
      for each of the target compounds and provided good linearity (r2>0.99).This
      method was precise (the intra and inter-day coefficient of variation was <20% at
      two different concentrations (0.40 and 3.20 ng/mL) and accurate (recovery ranged
      from 81% to 119%). The limits of detection obtained for BPA and its chlorinated
      derivatives ranged from 0.01 to 0.09 ng/mL. The limit of quantification for all
      the compounds validated at 0.40 ng/mL when using 500 MUL of milk was found to be
      suitable for the concentration existing in real samples. The analytical method
      developed in this study is in accordance with the requirements applicable to
      biomonitoring of BPA and its chlorinated derivatives in human breast milk.

PMID- 23141327
TI  - Multi-residue method for trace level determination of pharmaceuticals in
      environmental samples using liquid chromatography coupled to triple quadrupole
      mass spectrometry.
AB  - A multi-residue method for the simultaneous determination of more than 90
      pharmaceuticals in water samples was developed and validated. The developed
      method utilizes a single liquid chromatography-tandem mass spectrometry (LC
      MS/MS) run after sample enrichment using solid-phase extraction (SPE). The
      pharmaceuticals included in this method were chosen based on their potency
      (effect/concentration ratio) and potential to bioaccumulate in fish. Because the
      selection was based on ecotoxicological criteria and not on ease of detection,
      the pharmaceuticals have a wide range of physico-chemical properties and
      represent 27 distinct classes. No method for surface, waste water or similar
      matrices was previously described for 52 of the 100 target analytes. Four
      chromatographic columns were tested to optimize the separation prior to detection
      by mass spectrometry (MS). The resulting method utilizes a Hypersil Gold aQ
      column. Three different water matrices were tested during method validation:
      Milli-Q water, surface water (river water from the Umea River) and effluent from
      the Umea waste water treatment plant (WWTP). Four of the selected pharmaceuticals
      exhibited poor method efficiency in all matrices. Amiodarone, Dihydroergotamine,
      Perphenazine and Terbutalin were omitted from the final analytical method. In
      addition, five compounds were excluded from the method for surface water
      (Atorvastatin, Chloropromazin, Dipyridamol, Furosemid and Ranitidin) and three
      other pharmaceuticals (Glibenclamid, Glimepirid and Meclozine) from waste water
      method respectively. Absolute recoveries were above 70% for Milli-Q water,
      surface water, and sewage effluent for most pharmaceuticals. The limits of
      quantification (LOQs) ranged from 0.05 to 50 ng L(-1) (median 5 ng L(-1)). The
      use of matrix-matched standards led to the elimination of ionization enhancement
      or suppression. The recoveries of the method for real matrices were in the range
      of 23-134% for surface water (only three compounds were outside of the range of
      40-130%) and in the range of 47-162% for waste water (five compounds were outside
      of the range of 40-130% at lower validated concentration).

PMID- 23141328
TI  - Characterization and validation of ion mobility spectrometry in methamphetamine
      clandestine laboratory remediation.
AB  - This project evaluated the efficacy of ion mobility spectrometry (IMS) as a tool
      for determining remediation success at clandestine methamphetamine laboratory
      sites. Specifically, limits of detection (LOD), limits of quantitation (LOQ), and
      matrix effects were investigated as relevant to typical remediation sites and
      situations. The recoveries of pseudoephedrine and methamphetamine from a range of
      various surfaces likely to be found in a clandestine laboratory were examined.
      Portable IMS instruments with thermal desorption were found to be a reliable tool
      for evaluating the degree of remediation if sufficient procedural and
      instrumental controls are put into place. In general, detection limits were in
      the same range as state guidelines as well as laboratory methods using GC/MS and
      LC/MS. Direct vapor sampling can be used to detect high levels of methamphetamine
      and potential interferences, but cannot approach the detection limits needed for
      evaluation of remediation efforts. IMS cannot be used alone to determine the
      efficacy of remediation efforts; final confirmation using laboratory
      instrumentation is essential. For the purpose of this study, typical field
      settings of the IMS were used and the conditions were not optimized.

PMID- 23141329
TI  - Rapid determination of polycyclic aromatic hydrocarbons (PAHs) in tea using two
      dimensional gas chromatography coupled with time of flight mass spectrometry.
AB  - A simple, fast, and cost effective sample preparation procedure has been
      developed and validated for the determination of 15+1 European Union Polycyclic
      Aromatic Hydrocarbons (15+1 EU PAHs) in dried tea leave samples. Based on a
      critical assessment of several sample extraction/clean-up approaches, the method
      based on the ethyl acetate extraction followed by the use of PAHs dedicated
      cartridges with molecularly imprinted polymers (MIPs) has been found as an
      optimal alternative in terms of time demands and obtained good extract purity.
      For the final identification/quantification of target PAHs, two dimensional gas
      chromatography coupled to a time-of-flight mass spectrometry (GC*GC-TOFMS) was
      used. The performance characteristics of the overall analytical method for
      individual PAHs determined at three spiking levels (0.5, 2.5 and 5 MUg kg(-1))
      were in following ranges: limits of quantitation (LOQs) 0.05-0.2 MUg kg(-1),
      repeatabilities 2-9%, and recoveries 73-103%. The recoveries achieved by the
      newly developed sample preparation procedure when employed for naturally
      contaminated sample ("incurred" PAHs) were comparable to those obtained by other
      routinely used approaches employing sonication and/or pressurised liquid
      extraction for sample analytes isolation. The validated method was subsequently
      used for the determination of selected genotoxic PAHs in 36 samples of black and
      green tea obtained from the Czech retail market. The levels of SigmaPAH4 (sum of
      benzo[a]anthracene (BaA), chrysene (CHR), benzo[b]fluoranthene (BbFA) and
      benzo[a]pyrene (BaP)) in black and green tea leaves ranged from 7.4 to 700 MUg
      kg(-1) and from 4.5 to 102 MUg kg(-1), respectively. Contamination of tested tea
      samples by BaP was in the range of 0.2-152 MUg kg(-1).

PMID- 23141330
TI  - Progress and recent advances in fabrication and utilization of hypoxanthine
      biosensors for meat and fish quality assessment: a review.
AB  - This review provides an update on the research conducted on the fabrication and
      utilization of hypoxanthine (Hx) biosensors published over the past four decades.
      In particular, the review focuses on progress made in the development and use of
      Hx biosensors for the assessment of fish and meat quality which has dominated
      research in this area. The various fish and meat freshness indexes that have been
      proposed over this period are highlighted. Furthermore, recent developments and
      future advances in the use of screen-printed electrodes and nanomaterials for
      achieving improved performances for the reliable determination of Hx in fish and
      meat are discussed.

PMID- 23141331
TI  - Synthesis, characterization of conjugated oligo-phenylene-ethynylenes and their
      supramolecular interaction with beta-cyclodextrin for salicylaldehyde detection.
AB  - Four new conjugated oligo-phenylene-ethynylenes derivatives, N-methyl-4-(4
      acetylthiophenylethynyl)-1,8-naphthalimide (1), thioacetic acid S-[4-(4
      aminophenyl-ethynyl)phenyl]ester (2), 4-methylthiophenylethynylbenzenamine (3), N
      methyl-4-(4-methyl-thiophenyl-ethynyl)-1,8-naphthalimide (4), were synthesized by
      Sonogashira and Eglinton cross-coupling reactions. The structures of the four
      compounds were confirmed by (1)HNMR, (13)CNMR, MS and IR and their spectral
      characteristics were studied by ultraviolet and visible (UV) spectroscopy as well
      as fluorescence spectroscopy in different medium. It was found that the
      fluorescence properties of compounds 2 and 3 were notably improved in aqueous
      solutions in the presence of beta-cyclodextrin (beta-CD). Spectral analysis
      supported the suppositions that the fluorescence intensity enhancement was due to
      the formation of inclusion complex with beta-CD. The supramolecular interaction
      was investigated in detail and the reaction mechanism was provided. A
      salicylaldehyde determination method in aqueous medium was established based on
      the supramolecular complex of compound 3. Under the optimum conditions, the
      supramolecular complex exhibited a dynamic fluorescence response range for
      salicylaldehyde from 0.6 to 240*10(-6) molL(-1), with a detection limit of 1*10(
      8) molL(-1).

PMID- 23141332
TI  - Fast human serum profiling through chemical depletion coupled to gold
      nanoparticle-assisted protein separation.
AB  - The use of chemical protein depletion in conjunction with gold-based
      nanoparticles for fast matrix assisted laser desoption ionization time of flight
      mass spectrometry-based human serum profiling was assessed. The following
      variables influencing the process were optimized: (i) amount of nanoparticles,
      (ii) sample pH, (iii) amount of protein and (iv) incubation time. pH was found
      the most important factor to be controlled, with an optimum range comprised
      between 5.8 and 6.4. The minimum incubation time to obtain an adequate profiling
      was 30 min. Using this approach, serum from five patients with lymphoma, five
      patients with myeloma and from two healthy volunteers were correctly classified
      using Principal component analysis.

PMID- 23141333
TI  - Hollow fibre-based liquid-phase microextraction technique combined with gas
      chromatography-mass spectrometry for the determination of pyrethroid insecticides
      in water samples.
AB  - A simple, easy-to-use, efficient and environmentally friendly method has been
      developed for the simultaneous analysis of nine pirethroid pesticides in water
      samples by the combination of hollow fibre-based liquid-phase microextraction (HF
      LPME) and gas chromatography-mass spectrometry (GC/MS). For the developed method,
      nine pirethroid pesticides (esbiothrin, prallethrin, bifenthrin, tetramethrin,
      phenothrin, permethrin, cyfluthrin, cypermethrin and deltamethrin) were
      concentrated and well separated under optimal conditions. Several factors that
      influence the efficiency of HF-LPME were investigated and optimized by means of
      experimental design. The proposed method has good linearity in the concentration
      range of 10-400 MUg L(-1) with correlation coefficients between 0.995 and 0.999.
      Overall enrichment factors for the optimized method ranged from 139 to 255 times
      except for cypermethrin and deltamethrin which ranged from 35 to 128. Detection
      and quantitation limits of the chromatographic method were in the range of 0.002
      0.012 MUg L(-1) and 0.003-0.026 MUg L(-1) respectively, with RSD values between
      4.2% and 18.4%. The recoveries varied in the range of 69.4%-122.7% except for
      cypermethrin and deltamethrin (17.5%-64.1%) with relative standard deviations
      between 1.0% and 24.0% for intra and inter-day experiments at different
      concentrations (0.1 MUg L(-1), 0.5 MUg L(-1), 1 MUg L(-1)). The HF-LPME method
      optimized was applied to the analysis of three spiked real water samples with
      good results.

PMID- 23141334
TI  - Ability of various materials to detect explosive vapors by fluorescent
      technologies: a comparative study.
AB  - For the development of fluorescent sensors, one of the key points is choosing the
      sensitive material. In this article, we aim at evaluating, under strictly
      identical experimental conditions, the performance of three materials for the
      detection of dinitrotoluene (a volatile marker of trinitrotoluene) through
      different parameters: response time, fluorescence intensity, sensitivity,
      reversibility, reaction after successive exposures and long-term stability. The
      results are discussed according to the nature of the sensitive materials. This
      first study rendered it possible to select a conjugated molecule as the best
      sensitive material for the development of a lab-made prototype. In a second part,
      the selectivity of this particular sensitive material was studied and its ability
      to detect TNT could be demonstrated.

PMID- 23141335
TI  - Matrix-assisted laser desorption/ionisation time of flight spectrometry for the
      fast screening of oxosteroids using aromatic hydrated hydrazines as versatile
      probes.
AB  - To make the use of MALDI-based mass spectrometry feasible for the fast analysis
      of oxosteroids, three new aromatic probes have been designed to be used
      simultaneously as derivatisation agents and MALDI matrices. This concept brings a
      number of benefits: the sample handling is reduced, the workflow is less time
      consuming allowing high throughput and the interferences caused by the MALDI
      matrix are avoided. Identification was successfully attained for all oxosteroids
      used in this study. As proof-of-concept, the identification of oxosteroids in
      urine was performed to evaluate the robustness of the new methodology. The
      oxosteroids 17-alpha-methyltestosterone, nandrolone, boldenone, 17-alpha
      Trenbolone, fluoxymesterolone, mesterolone and bolasterone were identified in
      human urine at the minimum concentration level recommended by the world anti
      doping agency, 2 ng/mL.

PMID- 23141336
TI  - Synthesis and characterization of water-insoluble statistical copolymer and its
      application in the development of electrochemical DNA sensor.
AB  - Water-insoluble statistical copolymer was synthesized by copolymerization of
      methyl methacrylate (MMA) with 2-(dimethylamino)ethyl methacrylate (DMA) via
      group transfer polymerization (GTP). The DMA residues of the precursor P(MMA-co
      DMA) statistical copolymer were then quaternized by reacting with methyl iodide
      under mild conditions to get well-defined P(MMA-co-QDMA) cationic copolymer.
      Then, P(MMA-co-QDMA) copolymer was successfully used for surface modification of
      pencil graphite electrode (PGE) to develop a disposable DNA sensor. This P(MMA-co
      QDMA) copolymer modified electrode (q-PGE) was examined for electrochemical
      monitoring of DNA by using differential pulse voltammetry (DPV) in contrast to
      unmodified one. The effect of both DNA concentration and sonication time was also
      examined based on the response of q-PGE. The detection limit was calculated to be
      8.06 MUg/mL at q-PGE. Electrochemical impedance spectroscopy (EIS) was used for
      the characterization of the surface modification of q-PGE and consequently, the
      results were found to be in good agreement with the voltammetric measurements.

PMID- 23141337
TI  - Determination of 11 major and minor elements in chondritic meteorites by
      inductively coupled plasma mass spectrometry.
AB  - We have developed a new method for the quantification of 11 major and minor
      elements (Na, Mg, Al, P, S, K, Ca, Cr, Mn, Fe, and Ni) in chondritic meteorites
      by ICPMS using external calibration with a matrix-matched standard prepared from
      the Allende Standard Reference Meteorite. We have demonstrated the method's
      accuracy and assessed three different measures of precision by performing
      replicate dissolutions and analyses of 0.10-g samples of a homogenized samples of
      the CM2 meteorite Murchison and compared our results to literature values. We
      subsequently applied this method to the analysis of a set of four chondritic
      meteorites possessing a relatively wide range of chondritic compositions with
      results in accord with previously published values. Because our method is
      designed to use the same instrumentation and can use samples and standards
      prepared according to methods previously validated for the determination of a
      comprehensive suite of minor, trace, moderately and highly volatile trace
      elements (i.e., Li, Sc, Ti, V, Mn, Co, Cu, Zn, Ga, As, Se, Rb, Sr, Y, Zr, Nb, Mo,
      Ru, Pd, Ag, Cd, In, Sn, Sb, Te, Cs, Ba, all 14 naturally occurring lanthanoids,
      Hf, W, Re, Ir, Pt, Tl, Bi, Th, and U) it complements these methods and allows a
      single laboratory to determine the concentrations of 60 elements in
      semimicroscopic amounts of chondritic material.

PMID- 23141338
TI  - Graphene-carbon paste electrode for cadmium and lead ion monitoring in a flow
      based system.
AB  - An environment friendly electrode for determining Cd(2+) and Pb(2+) levels in an
      automated flow system was successfully developed. Cyclic voltammetry and square
      wave anodic stripping voltammetry (SWASV) coupled with sequential injection
      analysis (SIA) were employed to study the electrochemical behavior of the
      electrode. The in situ bismuth-modified graphene-carbon paste electrode (Bi-GCPE)
      exhibited excellent electrooxidation of Cd(2+) and Pb(2+) in the automated flow
      system with a significantly higher peak current for both metal ions compared with
      the unmodified CPE. The limits of detection from this method were 0.07 and 0.04
      MUg L(-1) for Cd(2+) and Pb(2+), respectively, with a linear oxidation peak
      current response for Cd(2+) and Pb(2+) in the range of 0.10-50.0 MUg L(-1) under
      optimum conditions. The Bi-GCPE was also applied for the determination of Cd(2+)
      and Pb(2+) in low- (tap water) and high- (sea bass fish and undulated surf clam
      tissues) matrix complexity samples by automated flow system. The recoveries were
      acceptable and ranged from 70.4% to 120% for Cd(2+) and 65.8% to 113.5% for
      Pb(2+).

PMID- 23141339
TI  - Reply to the responses on the comments on "Uncertainty profiles for the
      validation of analytical methods" by Saffaj and Ihssane.
AB  - Saffaj and Ihssane, recently proposed an uncertainty profile for evaluating the
      validity of analytical methods using the statistical methodology of gamma
      confidence beta-content tolerance intervals. This profile assesses the validity
      of the method by comparing the method measurement uncertainty to a predefined
      acceptance limit stating the maximum uncertainty suitable for the method under
      study. In this letter we comment on the response (T. Saffaj, B. Ihssane, Talanta
      94 (2012) 361-362) these authors have made to our previous letter (E. Rozet, E.
      Ziemons, R.D. Marini, B. Boulanger, Ph. Hubert, Talanta 88 (2012) 769-771). In
      particular, we demonstrate that beta-expectation tolerance intervals are
      prediction intervals, we show that beta-expectation tolerance intervals are
      highly useful for assessing analytical methods validation and for estimating
      measurement uncertainty and finally we show what are the differences and
      implications for these two topics (validation and uncertainty) when using either
      the methodology of beta-expectation tolerance intervals or the gamma-confidence
      beta-content tolerance tolerance interval one.

PMID- 23141340
TI  - Development of a fluid bed granulation process control strategy based on real
      time process and product measurements.
AB  - This article describes the results of three case studies conducted consecutively,
      in order to develop a process control strategy for a top-spray fluid bed
      granulation process. The use of several real-time particle size (i.e., spatial
      filter velocimetry and focused beam reflectance measurement) and moisture (i.e.,
      near infrared (NIR) and Lighthouse near infrared spectroscopy) analyzers was
      examined. A feed-forward process control method was developed, where in-line
      collected granulation information during the process spraying phase was used to
      determine the optimum drying temperature of the consecutive drying phase. Via
      real-time monitoring of process (i.e., spraying temperature and spray rate) and
      product (i.e., granule size distribution and moisture) parameters during the
      spraying period, the batch bulk density was predicted at the end of the spraying
      cycle, using a PLS model. When this predicted bulk density was not meeting the
      desired value, the developed control method allowed the calculation of an
      adjusted drying temperature leading to the desired batch bulk density at the end
      of the granulation process. Besides the development of the feed-forward control
      strategy, a quantitative PLS model for in-line moisture content prediction of the
      granulated end product was built using the NIR data.

PMID- 23141341
TI  - Enzyme-catalyzed assembly of gold nanoparticles for visualized screening of DNA
      base excision repair.
AB  - Activity screening of DNA base excision repair (BER) enzymes is a crucial step
      for understanding numerous fundamental biochemical processes. A novel label-free
      homogeneous technique is developed for visualized uracil-DNA glycosylase (UDG)
      activity assay using gold nanoparticles (AuNPs). This strategy relies on the
      enzyme-catalyzed assembly of AuNPs decorated with DNA probes. In the presence of
      endonuclease IV (an enzyme which can further hydrolyze the products from UDG
      catalyzed reaction), the substrate DNA selectively interacts with UDG followed by
      the efficient release of a single-strand probe. The released single-strand probe
      then makes the network-like assembly of decorated AuNPs to provide a visible
      signal for UDG activity. This strategy that can be performed in a label-free
      homogeneous assay format improved the duration, the simplicity and the throughput
      of UDG activity screening. The results provided in the present study revealed
      that this strategy could hold great potential as a robust, convenient and
      visualized platform for activity screening of uracil-DNA glycosylases with high
      selectivity and desirable sensitivity.

PMID- 23141342
TI  - A micro-flow-batch analyzer with solenoid micro-pumps for the photometric
      determination of iodate in table salt.
AB  - In this study, a micro-flow-batch analyzer (MUFBA) with solenoid micro-pumps for
      the photometric determination of iodate in table salt is described. The method is
      based on the reaction of iodate with iodide to form molecular iodine followed by
      the reaction with N,N-diethyl-p-phenylenediamine (DPD). The analytical signal was
      measured at 520 nm using a green LED integrated into the MUFBA built in the
      urethane-acrylate resin. The analytical curve for iodate was linear in the range
      of 0.01-10.0 mg L(-1) with a correlation coefficient of 0.997. The limit of
      detection and relative standard deviation were estimated at 0.004 mg L(-1)
      and<1.5% (n=3), respectively. The accuracy was assessed through recovery test
      (97.6-103.5%) and independent analysis by a conventional titrimetric method.
      Comparing this technique with the conventional method, no statistically
      significant differences were observed when applying the paired t-test at a 95%
      confidence level. The proposed microsystem using solenoid micro-pumps presented
      satisfactory robustness and high sampling rate (170 h(-1)), with a low reagents
      consumption and a low cost to build the device. The proposed microsystem is a new
      alternative for automatic determination of iodate in table salt, comparing
      satisfactory to the recently flow system.

PMID- 23141343
TI  - Mixed mode HILIC/anion exchange separations on latex coated silica monoliths.
AB  - Bare silica monoliths do not possess anion exchange sites hence they show low
      retention for anions. Moreover, bare silica monoliths show low retention in
      hydrophilic interaction liquid chromatography (HILIC). Coating the silica surface
      with cationic nanoparticles e.g. AS9-SC (latex A), AS12A (latex B) and DNApac
      (latex C) increases the thickness of the water layer on the Onyx silica monolith
      8-10 times enabling HILIC retention when a high % acetonitrile (ACN) mobile phase
      is used. The formed water layer by itself is not sufficient to perform good
      separation of the studied anions (acetate, formate, nitrate, bromate, thiocyanate
      and iodide). On the other hand, the latex nanoparticles introduce positively
      charged sites, making anion exchange chromatography possible, with the anion
      exchange capacity varying with the latex adsorbed (44.1 +/- 0.2, 4.4 +/- 0.1 and
      14.0 +/- 0.7 MUeq/column for latex A, B and C, respectively). Latex A
      nanoparticles which provided the highest ion exchange capacity separated all
      tested anions with reasonable resolution. Fast separation (2.5 min) of acetate,
      formate, nitrate, bromate, thiocyanate and iodide was performed using the latex A
      coated silica monolith. The obtained efficiencies are 13,000-50,000 plates/m at 3
      mL/min with a minimum resolution of 0.85. Retention is mixed mode under HILIC
      conditions with HILIC dominating for the kosmotropic anions and ion exchange
      dominating for the chaotropic anions. The two different brands of silica
      monoliths (Merck Chromolith and Phenomenex Onyx) coated with the same latex A
      nanoparticles displayed similar water layer volumes, ion exchange capacity and
      selectivity.

PMID- 23141344
TI  - A modified QuEChERS method as sample treatment before the determination of
      isoflavones in foods by ultra-performance liquid chromatography-triple quadrupole
      mass spectrometry.
AB  - This paper reports the development of an analytical method for the determination
      of isoflavones in legumes using LC-MS/MS. A modified approach of the QuEChERS
      methodology was used to extract the analytes from the food samples. The proposed
      method includes a two-step extraction process and allows the determination of
      isoflavones in pulses without the need of a clean-up step. Use of this
      methodology for the extraction of natural occurring substances provides
      advantages such as simplicity and ease of use, especially taking into account the
      complexity of food matrices. The method was applied successfully for the
      determination of eight isoflavones, including aglycones and glucosides, in
      legumes of Spanish origin (chickpeas, lentils and beans from the region of
      Castilla y Leon). The target compounds were the glucosides daidzin, glycitin and
      genistin, and the aglycones daidzein, glycitein, genistein, formononetin, and
      biochanin A. The detection limits were in the 0.7 MUg L(-1) to 1.5 MUg L(-1)
      range for formononetin and glycitin respectively. Recoveries ranged from 72% to
      119%, and standard deviations lower than 25% were obtained for the inter-day
      precision. The method described is precise, selective and not time-consuming.

PMID- 23141346
TI  - Simultaneous analysis of seven oligopeptides in microbial fuel cell by micro
      fluidic chip with reflux injection mode.
AB  - In this work, a reflux injection mode for the cross form micro-fluidic chip was
      studied. This injection mode could flexibly control the length of sample plug
      from less than one channel width (<83 MUm) to tens of channel widths (millimeter
      sized) by adjusting the injection time. Namely, the separation resolution or
      sample detection sensitivity could be selectively improved by changing injection
      time. Composed of four steps, the reflux injection mode alleviated the
      electrophoretic sampling bias and prevented sample leakage successfully. On a
      micro-fluidic chip coupled with laser induced fluorescence (LIF) detector, the
      injection mode was applied to separate seven oligopeptides, namely GG, GL, RPP,
      KPV, VKK, WYD and YWS. All analytes were completely separated and detected within
      12 min with detection limits of 25-625 nmol/L. At last, the proposed method had
      been successfully applied to detect oligopeptides consumed by bacillus
      licheniformis in anode chamber of microbial fuel cell (MFC) to study the effect
      of oligopeptides on the MFC running.

PMID- 23141345
TI  - Quantitative structure-retention relationships of azole antifungal agents in
      reversed-phase high performance liquid chromatography.
AB  - Artificial neural network (ANN) is a learning system based on a computational
      technique which can simulate the neurological processing ability of the human
      brain. It was employed for building of the quantitative structure-retention
      relationships (QSRRs) model of antifungal agents-imidazoles or triazoles by
      structure. Computed molecular descriptors together with the percentage of
      acetonitrile in mobile phase (v/v) and buffer pH, being the most influential HPLC
      factors, were used as network inputs, giving the retention factor as model
      output. The multilayer perceptron network with a 9-5-1 topology was trained by
      using the back propagation algorithm. Good correlation between experimentally
      obtained data and ones predicted by using QSRR-ANN on previously unseen data sets
      indicates good predictive ability of the model.

PMID- 23141347
TI  - Monolithic poly (SPE-co-BVPE) capillary columns as a novel hydrophilic
      interaction liquid chromatography stationary phase for the separation of polar
      analytes.
AB  - A novel hydrophilic interaction liquid chromatography (HILIC) stationary phase
      was prepared by the co-polymerisation of zwitterionic N,N'-dimethyl-N
      methacryloxyethyl-N-(3-sulfopropyl) ammonium betaine (SPE) and the crosslinker
      1,2-bis(p-vinylphenyl) ethane (BVPE) in the presence of the porogens, toluene and
      methanol. Monolithic columns were produced by carrying out the alpha,alpha'
      azoisobutyronitrile (AIBN) initiated reaction for 1, 2, 4, 8 and 12 h inside a
      200 MUm i.d. fused silica capillary at 75 degrees C (water bath). The optimum
      polymerisation time was shown to be 2 h, as this resulted in good porosity, due
      to enlarged flow-channels and the presence of a higher proportion of mesopores
      provided a relatively larger surface area than the other columns. The
      chromatographic properties of the optimised poly (SPE-co-BVPE) monolithic column
      were evaluated with test mixtures containing both basic and neutral compounds in
      the HILIC gradient separation mode. This produced relatively sharp peaks (average
      peak width at half height=0.1 min) with average asymmetry factors of 1.4 and
      baseline resolution was obtained for all the compounds. Using the isocratic
      separation of the test mixture, the number of theoretical plates (N) per metre
      calculated was between 26,888 and 35,930 by using average values obtained for
      triplicate injections of the compounds thiourea, toluene and acrylamide.

PMID- 23141348
TI  - Separation and preconcentration of 2,3,7,8-tetrachlorodibenzo-p-dioxin in blood
      samples by inclusion emulsion membranes and its determination by gas
      chromatography.
AB  - The nano-mediated preconcentration of 2,3,7,8-tetrachlorodibenzo-p-dioxin from
      blood samples was reported by inclusion-facilitated emulsion liquid membrane
      process. The novelty of this study was application of nano-baskets of calixarene
      and emulsion liquid membranes in selective and efficient preconcentration of
      2,3,7,8-tetrachlorodibenzo-p-dioxin. For this aim, four derivatives of p-tert
      calix[4]arene bearing different sulfonamide moieties were synthesized and their
      inclusion-extraction parameters were optimized including calixarenes' scaffold
      and concentration (3, 4 wt%), diluent type in membrane, phase and treat ratios
      (0.8 and 0.3), mixing speed (300 rpm), and initial solute concentrations (0.1-10
      pg g(-1)). The extraction efficiency was determined by dioxin's concentration
      using gas chromatography equipped with electron capture detector and the results
      revealed that in optimized operating conditions, the preconcentration of 2,3,7,8
      tetrachlorodibenzo-p-dioxin was improved and the limit of detection decreased.

PMID- 23141349
TI  - Development and optimization of a method for the determination of
      Cylindrospermopsin from strains of Aphanizomenon cultures: intra-laboratory
      assessment of its accuracy by using validation standards.
AB  - The occurrence of cyanobacterial blooms in aquatic environments is increasing in
      many regions of the world due to progressive eutrophication of water bodies.
      Because of the production of toxins such as Cylindrospermopsin (CYN),
      contamination of water with cyanobacteria is a serious health problem around the
      world. Therefore it is necessary to develop and validate analytical methods that
      allow us to quantify CYN in real samples in order to alert the public of this
      toxin. In this work, an analytical method has been developed an optimized for the
      determination of CYN from Aphanizomenon ovalisporum cultures. The analytical
      procedure is based on solvent extraction followed by a purification step with
      graphitized cartridges and CYN quantification by LC-MS/MS. The extraction and
      purification steps were optimized using a two-level full factorial design with
      replications. A suitable and practical procedure for assessing the trueness and
      precision of the proposed method has been applied by using validation standards.
      The method has been suitably validated: the regression equation was calculated
      from standards prepared in extracts from lyophilized M. aeruginosa PCC7820
      (r(2)>=0.9999) and the linear range covered is from 5 to 500 MUg CYN/L,
      equivalent to 0.18-18.00 MUg CYN/g dry weight lyophilized cells. Limits of
      detection and quantification were 0.04 and 0.15 MUg CYN/g, respectively, the
      recovery range (%) oscillated between 83 and 94% and intermediate precision (RSD
      %) values from 5.6 to 11.0%. Moreover, the present method showed to be robust for
      the three factors considered: the batch of the graphitized carbon cartridges, the
      flow rate of the sample through the cartridge, and the final re-dissolved water
      volume after SPE treatment, which permits its validation. The validated method
      has been applied to different lyophilized cultures of A. ovalisporum (LEGE X-001)
      to evaluate CYN content. This procedure can be used for determining CYN in
      lyophilized natural blooms samples in environmental studies.

PMID- 23141350
TI  - HPLC/ELSD analysis of amidated bile acids: an effective and rapid way to assist
      continuous flow chemistry processes.
AB  - The employment of the flow N-acyl amidation of natural bile acids (BAs) required
      the in-line connection with suitable analytical tools enabling the determination
      of reaction yields as well as of the purity grade of the synthesized glyco- and
      tauro-conjugated derivatives. In this framework, a unique HPLC method was
      successfully established and validated for ursodeoxycholic (UDCA),
      chenodeoxycholic (CDCA), deoxycholic (DCA) and cholic (CA) acids, as well as the
      corresponding glyco- and tauro-conjugated forms. Because of the shared absence of
      relevant chromophoric moieties in the sample structure, an evaporative light
      scattering detector (ELSD) was profitably utilized for the analysis of such
      steroidal species. For each of the investigated compounds, all the runs were
      contemporarily carried out on the acidic free and the two relative conjugated
      variants. The different ELSD response of the free and the corresponding
      conjugated BAs, imposed to build-up separate calibration curves. In all the
      cases, very good precision (RSD% values ranging from 1.04 to 6.40% in the long
      period) and accuracy (Recovery% values ranging from 96.03 to 111.14% in the long
      period) values along with appreciably low LOD and LOQ values (the former being
      within the range 1-27 ng mL(-1) and the latter within the range 2-44 ng mL(-1))
      turned out.

PMID- 23141351
TI  - Determination by GC-MS-SIM of furanoditerpenes in Pterodon pubescens Benth.:
      development and validation.
AB  - The crude hydroalcoholic extract from fruits of P. pubescens is widely used
      because of its anti-rheumatic, antinociceptive and anti-inflammatory activities.
      Furanoditerpenes have a vouacapan skeleton and are involved with the
      pharmacological activity of the oil extracted from P. pubescens fruits.
      Furanoditerpenes methyl 6alpha-acetoxy-7beta-hydroxyvouacapan-17beta-oate and
      methyl 6alpha-hydroxy-7beta-acetoxyvouacapan-17beta-oate from P. pubescens were
      isolated and identified. The present study developed and validated a GC-MS-SIM
      method for the separation and quantification of vouacapan constituents in a
      semipurified extract from P. pubescens fruits. The GC-MS analyses were carried
      out using a system equipped with a HP-5 capillary column (30 m * 0.25 mm).
      Temperature program: 100 degrees C (4 degrees C min(-1))-270 degrees C (5 min),
      injector 260 degrees C, detector 270 degrees C. Helium was used as the carrier
      gas (0.7 bar, 1 mL min(-1)). The MS was taken at 70 eV. Scanning speed was 0.5
      scans s(-1), from 50 to 650. Sample volume was 1 MUL. Split 1:20. Analyses for
      validation of methodology were conducted by GC-MS-SIM (Single Ion Monitoring),
      where the ions monitored were 131, 145 and 146 (between 43 and 44.5 min), 105,
      145 and 197 (from 44.5 to 45.3 min) and 131, 178 and 312 (from 45.3 to 48.5
      min).Validation of the analytical method was based on the following parameters:
      linearity, robustness, limits of detection and quantification, precision (within
      day and between-day variabilities), recovery and stability. The method was linear
      over a range of 12.81-2.56 MUgammaMULambda(-1) of vouacapan 1, 112.78-22.56 MUg
      mL(-1) of vouacapan 2, and 333.34-66.67 MUg mL(-1) of vouacapans 3 and 4, with
      detection limits of 0.39, 3.45 and 9,44 MUg mL(-1) and quantification limits of
      1.19, 10.47 and 28.62 MUg mL(-1), respectively. Recovery values were 100.69%,
      97.48% and 96.98% for vouacapans 1, 2 and 3-4, respectively. Thus, the method was
      efficient to separate and quantify furanoditerpenes in the extract or fraction.

PMID- 23141352
TI  - Highly sensitive hydrazine chemical sensor fabricated by modified electrode of
      vertically aligned zinc oxide nanorods.
AB  - A highly sensitive, reliable and reproducible hydrazine chemical sensor was
      fabricated using vertically aligned ZnO nanorods (NRs) electrode. The low
      temperature hydrothermal process was adopted to synthesize the vertically aligned
      ZnO NRs on fluorine doped tin oxide (FTO) glass. The morphological
      characterizations revealed the vertical arrangement of highly dense ZnO NRs on
      FTO substrates. The ultraviolet diffused reflectance spectroscopy (UV-DRS) of
      aligned ZnO NRs electrode obtained the band gap of ~3.29eV which was close to
      that of bulk ZnO nanomaterials. The synthesized aligned ZnO NRs electrode was
      directly used to elucidate the chemical sensing performance towards the detection
      of hydrazine by simple current-voltage (I-V) characteristics. The aligned ZnO NRs
      electrode based hydrazine chemical sensor presented a significantly high
      sensitivity of ~4.42446*10(-5) A mM(-1) cm(-2) and the detection limit of ~515.7
      MUM with a correlation coefficient (R) of ~0.73297 and a short response time
      (10s). The electrochemical analysis of vertically aligned ZnO NRs electrode in
      the presence of hydrazine showed the increased current with high height of anodic
      peak which confirmed the involvement of high electron transfer process via high
      electrocatalytic activity of the electrode.

PMID- 23141353
TI  - Isolation of saccharides in dairy and soy products by solid-phase extraction
      coupled with analysis by ligand-exchange chromatography.
AB  - The present study reports an improved method to quickly and reproducibly isolate
      the saccharides from a variety of dairy and soy products utilizing reversed-phase
      solid-phase extraction to quantitatively remove fats, fatty acids, and lipids
      followed by desalination and deproteinization by ion-exchange solid-phase
      extraction with no loss of saccharides during extraction. Analysis of the
      isolated saccharides was performed by ligand-exchange HPLC. The method presented
      requires no prolonged heating (thus protecting the saccharides from hydrolysis or
      isomerization), uses benign reagents, and realizes a significant time savings
      over existing methods. The isolation and analysis of monosaccharides (glucose,
      galactose and fructose), disaccharides (lactose and sucrose), and polysaccharides
      (raffinose and stachyose) from dairy products (whole, reduced fat, and lactose
      free milk and yogurt), infant formula (powdered and premixed), and soy beverages
      were studied in this investigation with recoveries ranging from 88% to 110% in
      all products studied. We also applied the method to quickly discriminate
      authentic soy milk from a soy beverage, branded as soy milk.

PMID- 23141354
TI  - A gas chromatography-mass spectrometry multi-target method for the simultaneous
      analysis of three classes of metabolites in marine organisms.
AB  - In this work a fast and simple multi-target gas chromatography-mass spectrometry
      (GC-MS) method for the simultaneous detection and absolute quantification of
      amino acids, fatty acids, sterols and lupanes in marine organisms is proposed.
      The methodology was applied to the characterization of the echinoderm
      Marthasterias glacialis Linnaeus spiny sea star extracts. The main factors
      influencing the extraction of target compounds were evaluated by using different
      extraction procedures, solvent systems and temperature conditions and a
      comparison with a reference technique was performed. The most suitable procedure,
      capable of successfully extract the three classes of target compounds, was
      ethanol as solvent at 40 degrees C under magnetic stirring. Good analytical
      parameters were obtained since calibrations curves for the 40 compounds under
      analysis (15 amino acids, 16 fatty acids, 6 sterols and 3 lupanes) showed
      regression coefficients (r(2)) ranging from 0.9844 to 0.9978, with low RSD (from
      0.00 to 9.45%), and detection limits varying from 0.03 to 15.40 MUg/L. The RSD
      values for intra- and interday variations studies were also good (RSD<13.5%, for
      both) and recoveries were higher than 92%. Variation in samples from different
      harvests and origins and their chemical composition during the year is reported.
      The fact that no previous treatment of samples is required can make this a useful
      technique for metabolite profiling in marine organisms, among others, both in
      biomedical and nutritional studies. Moreover, due to the fast and robust
      character of the proposed method it seems to be suitable for the implementation
      as routine analysis.

PMID- 23141355
TI  - Simultaneous determination of Hg(II) and Zn(II) using a GFP inspired chromophore.
AB  - A dual-function chemosensor for Hg(2+) and Zn(2+) ions, inspired by the green
      fluorescent protein (GFP) chromophore, was designed and synthesized, which could
      specifically recognize Zn(2+) through an "OFF-ON" fluorescence mechanism due to
      the restriction of the free rotation of the aryl-alkene bond, whilst also
      producing a selective visible colorimetric response from yellow to pink with
      Hg(2+) ions. The response upon exposure to Zn(2+) and Hg(2+) is instantaneous,
      and the detect limits of Zn(2+) and Hg(2+) are 2.18*10(-8) M and 4.91*10(-7) M
      respectively.

PMID- 23141356
TI  - Inexpensive optical system for microarray ELISA.
AB  - The use of antibody-based diagnostic testing has increased significantly over the
      past decade, giving rise to a wide range of diagnostic devices. At one end of the
      cost-range are rapid inexpensive point-of-care tests based on
      immunochromatographic strips which provide a qualitative positive or negative
      test outcome. On the other hand, quantitative tests generally require the use of
      dedicated and expensive laboratory instruments. There remains a need for
      diagnostic instruments and tests that can provide quantitative assessment of
      disease markers at low cost. This paper describes the development of a novel low
      cost optical device for reading colorimetric and fluorescent immunodiagnostic
      test results. This portable instrument uses a webcam to capture test results from
      a specially designed 16-well slide containing a miniaturized array of test spots.
      Arrays are illuminated with either LEDs or lasers, while transmitted or emitted
      light is captured through a long-pass filter, allowing two different types of
      optical measurement to be performed within the same device. This device was used
      to read results from an array of antibodies conjugated with either an enzymatic
      or fluorescent tag resulting in a colored or fluorescent readout.

PMID- 23141357
TI  - Bisphenol A-glucuronide measurement in urine samples.
AB  - Bisphenol A (BPA), is one of the most abundant endocrine disruptors that are
      present in our environment, and has been repeatedly detected in most human
      biological samples. As it has been suggested that part of the BPA measured in
      human samples is due to contamination during samples collection or laboratory
      measurements, we have developed a specific radioimmunoassay for the measurement
      of BPA-glucuronide (BPA-G), the main endogenous metabolite of BPA in urine. We
      used a polyclonal anti-BPA antibody which has a 95% cross reactivity with BPA-G,
      and insignificant cross reactivity with most analogous BPA phenolic structures.
      To eliminate unconjugated BPA from urine samples, an extraction step with
      dichloromethane was required. The method proved to be valid, precise and accurate
      in the range of 0.05 MUg/L to 5 MUg/L. With this method, we measured BPA-G in 163
      urine samples from a hospital population. We detected BPA-G in all samples, with
      mean values of 4.64 MUg/L. In conclusion, the present radioimmunoassay is a
      useful tool for the screening of BPA exposure in human populations encompassing
      the problem of eventual contamination from laboratory manipulation.

PMID- 23141358
TI  - Quantification of ethanol in petrol-ethanol blends: use of Reichardt's E(T)(30)
      dye in introducing a petrol batch independent calibration procedure.
AB  - Petroleum fuels are generally non-polar. The presence of ethanol in the petrol
      ethanol fuel blends increases the polarity of the fuel blend. It was observed
      that absorption spectral shift of the Reichardt's E(T)(30) dye is sensitive to
      the petrol-ethanol blend polarity. It was also found that E(T)(30) dye has a
      characteristic lambda(max) of absorption in petrol-ethanol blends irrespective of
      the petrol batch with which blends were prepared. In the present work, a
      sensitive analytical method for the petrol batch independent quantification of
      ethanol content in petrol-ethanol blends has been developed.

PMID- 23141359
TI  - A novel matrix additive, MCM-41-type mesoporous silica nanoparticles, used for
      analysis of peptides by MALDI-FT/ICRMS.
AB  - Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) was
      thought to be unsuitable for the analysis of low-molecular-weight species since
      matrix peak noise made it difficult to identify analyte ions. In this study, MCM
      41-type mesoporous silica nanoparticles (MSNs) were used as a matrix additive
      with saturated 2,5-dihydroxybenzoic acid (DHB) or alpha-cyano-4-hydroxycinnannic
      acid (CHCA) solution for the analysis of six peptides of a wide range molecular
      weight, Leu-Val, Phe-Val, Lue-Phe, bradykinin fragment 1-7, angiotensin II and
      ACTH fragment 18-39. It was shown that MSNs were capable of reducing matrix peaks
      with laser power lower than 34% of saturated DHB especially for low polarity
      analyte or CHCA especially for high polarity analyte with molecular weight less
      than 500 regardless of the analyte-to-matrix ratio. In addition, MSNs could
      suppress ionization of oligopeptide and polypeptide. The way MSN exerted its
      effect was supposed to be via attraction between surface silanol groups and the
      analyte.

PMID- 23141360
TI  - Determination of labile barium in petroleum-produced formation water using paper
      based DGT samplers.
AB  - A polyacrylamide hydrogel containing the Chelex-100 resin has traditionally been
      used as the binding agent for the diffusion gradients in thin films (DGT)
      technique. The Chelex-100 resin, although important for the determination of
      various transition metals, is unsatisfactory for the determination of alkaline
      earth metals, particularly Ba. In this paper, a cellulose membrane, treated with
      phosphate (P81 membrane), was evaluated as a binding agent for DGT devices for
      the determination of Ba in produced formation water (PFW) samples. In addition,
      diffusive layers of filter paper (cellulose) were tested to diffuse Ba through
      the DGT devices. Experiments to evaluate the key variables of the technique (pH,
      deployment time, and ionic strength/salinity) were performed. The Ba sampled by
      these DGT devices was measured using inductively coupled plasma optical emission
      spectrometry. Aiming to generate information (related to bioavailability of Ba)
      on the reuse of PFW for irrigation, the determination of Ba in onshore and
      offshore samples was performed. The new approach was effective for determination
      of Ba in onshore samples. To determine Ba in offshore samples, it was necessary
      to use an alternative calibration procedure due to the high NaCl concentration in
      these samples.

PMID- 23141361
TI  - Solid phase extraction of copper traces using poly(styrene-divinylbenzene)
      membrane disks modified with pyridoxal salicyloylhydrazone in water samples.
AB  - A simple technique for the isolation, concentration and matrix simplification of
      Cu(II) ion in natural waters is proposed. This method has been developed using
      poly(styrene-divinylbenzene) membrane disks modified with the synthesized ligand
      pyridoxal salicyloylhydrazone (PSH). The retained ions on the disks were eluted
      with 10 mL 1 mol L(-1) HNO(3) and measured by flame atomic absorption
      spectrometry at 324.8 nm. The influence of pH, amount of ligand, type and amount
      of eluent for the stripping of copper ion from the membrane over extraction
      efficiency were evaluated. Extraction efficiencies >99% were obtained by elution
      of the disks with minimal amount of solvent with a preconcentration factor up to
      100. The precision of the method for 10 replicate measurements of aqueous
      solutions containing 40 MUg L(-1) Cu(II) was 1.5% at significance level of 95%.
      The breakthrough volume for 5 MUg of Cu(II) was found to be 1000 mL and the
      detection limit of the method was 4 ng L(-1) of metal ion. The present method was
      successfully applied to the extraction and determination of copper in lake and
      sea waters.

PMID- 23141362
TI  - Screening of edible oils for polycyclic aromatic hydrocarbons using microwave
      assisted liquid-liquid and solid phase extraction coupled to one- to three-way
      fluorescence spectroscopy analysis.
AB  - The potential of microwave-assisted liquid-liquid and solid phase extraction
      coupled with fluorescence spectroscopy and employing one- to three-way spectral
      data was assessed in terms of their capacity for the rapid detection of heavy
      polycyclic aromatic hydrocarbons (PAHs) in olive and sunflower oils. Tocopherols
      and pigments groups (chlorophyll and pheophytin) present in oil matrices were the
      main interference compounds in the detection of PAHs using fluorescence
      spectroscopy. Partial spectral overlap and inner-filter effects were observed in
      the emission range of the analytes. The effectiveness of removing these
      interferences using solid phase extraction (silica, C18 and graphitized carbon
      black) was examined. Solid phase extraction with silica was the most effective
      method for the removal of pigments and tocopherol and allowed for the detection
      of PAHs in edible oils using fluorescence spectroscopy. The limit of detection
      was observed to depend on the use of one-, two- or three-way fluorescence
      spectral data in the range of 0.8 to 7.0 MUg kg(-1). The individual recoveries of
      PAHs following the microwave-assisted L-L extraction and SPE with silica were
      assessed using HPLC-FD with satisfactory results.

PMID- 23141363
TI  - Magnetic stirring-assisted dispersive liquid-liquid microextraction followed by
      high performance liquid chromatography for determination of phthalate esters in
      drinking and environmental water samples.
AB  - A simple, fast and efficient method for the preconcentration of phthalate esters
      (PEs) in water samples was developed using magnetic stirring-assisted dispersive
      liquid-liquid microextraction (MSA-DLLME) followed by high performance liquid
      chromatography coupled with ultraviolet detection (HPLC-UV). This novel
      microextraction method is based on the fast injection of extracting solvent into
      the aqueous solution, which is being stirred by a magnetic stirrer, to form a
      cloudy binary component solvent (aqueous solution:extracting solvent) system. The
      extraction parameters such as type and volume of extracting solvent, pH of
      sample, salt addition, extraction time and stirring rate were optimized. Under
      the optimal conditions (extracting solvent: 200 MUL dodecane; pH of sample: 6.5;
      extraction time: 5 min; stirring rate: 1000 rpm), linearity was observed in the
      range of 2-1000 MUg L(-1) for dimethyl phthalate (DMP) and 1-1000 MUg L(-1) for
      diethyl phthalate (DEP), benzyl butyl phthalate (BBP) and di-n-butyl phthalate
      (DBP) with correlation determination values above 0.99 for them. The limits of
      detection and quantification were ranged from 0.13 to 0.38 MUg mL(-1) and 0.43 to
      1.27 MUg mL(-1), respectively. The ranges of intra-day and inter-day precisions
      (n=5) at 100 MUg L(-1) of PEs were 1.50-2.65% and 2.31-3.35%, respectively.
      Finally, the MSA-DLLME method was successfully applied for preconcentration of
      PEs in drinking and environmental water samples.

PMID- 23141364
TI  - A paper-based device for measurement of reactive phosphate in water.
AB  - The preparation and evaluation of a simple paper-based device for the
      determination of reactive phosphate in natural and soil waters based on the
      formation of phosphomolybdenum blue is reported. Hydrophilic reagent zones were
      defined by printing filter paper with a hydrophobic paper-sizing agent using an
      inkjet printer. The molybdate/potassium antimony(III)-tartrate reagent and
      ascorbic acid reductant merged together from adjacent hydrophilic zones after
      spotting the liquid sample onto the paper. The colour intensity of the
      phosphoantimonylmolybdenum blue complex produced was measured using a flat bed
      scanner. Under optimal conditions, the paper-based device is characterised by a
      working range of 0.2-10 mg L(-1) P, limits of detection and quantitation of 0.05
      and 0.16 mg L(-1) P, respectively, and repeatability of less than 2% RSD at 1 and
      5 mg L(-1) P (n=10 and 8). There was no significant difference between the
      results obtained using the paper-based device and reference methods (t=0.0135, P
      (T<=t) two-tail=0.9892, df=38). In its optimum form, the paper-based device was
      stable for up to 15 day under ambient conditions, and up to 122 day when stored
      at <=-20  degrees C. The small dimensions, minimal reagent consumption, low cost
      (a few cents), ease of operation and favourable analytical performance make the
      proposed paper-based device attractive for on-site environmental monitoring and
      analysis.

PMID- 23141365
TI  - Student attrition in the Ontario midwifery education programme.
AB  - OBJECTIVE: to identify the factors associated with student withdrawal during
      their university training. DESIGN: an Internet-based survey questionnaire was
      designed and administered. SETTING: two universities in Ontario, Canada.
      PARTICIPANTS: senior level students in years three and four, graduates of the
      programme and those students that withdrew prior to graduation. FINDINGS:
      students who withdrew from the programme were more likely to report not feeling
      academically supported and not being prepared for the time commitments required.
      Students with the greatest risk for leaving the programme were those that took a
      leave of absence, over half of which were maternity leaves. CONCLUSION: having
      identified those significant factors associated with student attrition, we can
      now begin to develop specific interventions to improve retention rates.

PMID- 23141366
TI  - Application of a novel design method for knee replacements to achieve normal
      mechanics.
AB  - PURPOSE: The purpose of this study was to utilize a novel method for the design
      of total knee replacements for use in the absence of the cruciate ligaments, with
      the design criteria of reproducing the medial stability and lateral mobility
      characteristics of the normal anatomic knee. SCOPE: The starting point was a
      femoral component with surfaces approximating anatomic. This surface was moved
      into multiple positions describing a neutral path of motion and laxity about the
      neutral path. The distal part of the femoral composite was then used to define
      the tibial surface. By varying the femoral design, different tibial surfaces were
      produced. The reference design featured a dished medial tibial surface and a
      shallow lateral tibial surface, but this provided limited motion guidance. To
      provide further guidance, two types of design were generated, one using
      intercondylar guide surfaces, the other providing guidance from the condylar
      surfaces themselves. CONCLUSIONS: The design method was capable of generating a
      range of total knee surfaces which could potentially return the arthritic knee to
      more normal function.

PMID- 23141367
TI  - Predicting the evolution of low back pain patients in routine clinical practice:
      results from a registry within the Spanish National Health Service.
AB  - BACKGROUND CONTEXT: The Spanish National Health Service (SNHS) is a tax-funded
      public organization that provides free health care to every resident in Spain.
      PURPOSE: To develop models for predicting the evolution of low back pain (LBP) in
      routine clinical practice within SNHS. STUDY DESIGN: Analysis of a prospective
      registry in routine clinical practice, in 17 centers across SNHS. PATIENT SAMPLE:
      Patient sample includes 4,477 acute and chronic LBP patients treated in primary
      and hospital care. OUTCOME MEASURES: Pain and disability, measured through
      validated instruments. METHODS: Patients treated for LBP were assessed at
      baseline and 3 months later. Data gathered were the following: sex, age,
      employment status, duration of pain, severity of LBP, pain down to the leg (LP)
      and disability, history of lumbar surgery, diagnostic procedures undertaken,
      imaging findings, and treatments used throughout the study period. Three separate
      multivariate logistic regression models were developed for predicting a
      clinically relevant improvement in LBP, LP, and disability at 3 months. RESULTS:
      In total, 4,261 patients (95.2%) attended follow-up. For all the models,
      calibration was reasonable and the area under the receiver operating
      characteristic curve was >=0.640. For LBP, LP, and disability, factors associated
      with a higher probability of improvement at 3 months were the following: not
      having undergone lumbar surgery, higher baseline scores for the corresponding
      variable, lower ones for the rest, and being treated with neuroreflexotherapy.
      Additional factors were the following: for LBP, shorter pain duration; for LP,
      not undergoing electromyography; and for disability, shorter pain duration, not
      being diagnosed with disc degeneration, and being treated with muscle relaxants
      and not opioids. CONCLUSIONS: A prospective registry can be used for developing
      predictive models to quantify the odds that a given LBP patient will experience a
      clinically relevant improvement. This may empower patients for an informed shared
      decision making.

PMID- 23141368
TI  - The Neck Pain Driving Index (NPDI) for chronic whiplash-associated disorders:
      development, reliability, and validity assessment.
AB  - BACKGROUND CONTEXT: Driving is a functional complaint of many individuals with
      chronic whiplash-associated disorders (WAD). Current driving scales do not
      include the most troublesome driving tasks for this group, which suggests that a
      new tool is required to assess perceived driving difficulty in this population.
      PURPOSE: To develop a Neck Pain Driving Index (NPDI) to assess the degree of
      perceived driving difficulty for individuals with chronic WAD and evaluate the
      reliability and validity of the NPDI. STUDY DESIGN: Descriptive/survey. PATIENT
      SAMPLE: An external panel of 15 researchers/clinicians and 87 participants with
      chronic WAD. OUTCOME MEASURES: The NPDI and a 0 to 10 numeric rating scale (NRS)
      of perceived driving difficulty (0, no difficulty and 10, maximum difficulty).
      METHODS: Phase 1 included the construction of a preliminary NPDI and content
      validity assessment of question items by a 15-member external panel.
      Comprehension was evaluated by seven participants with chronic WAD. In Phase 2,
      the final version of the NPDI was developed via descriptive analysis and
      assessment of internal consistency using responses of 87 participants with
      chronic WAD. Subsequently, the convergent validity was assessed using NRS scores.
      Test-retest reliability at 1 month was investigated in 25 of the 87 participants.
      Psychometric properties of the driving tasks in the final NPDI were categorized
      by the external panel, based on the hierarchal Michon model of driving task
      performance levels. An additional symptom section was developed to better
      understand the reasons for driving difficulties. RESULTS: The final NPDI included
      12 driving tasks, which scored at least 80% on the content validity index (CVI),
      ensuring content validity. The NPDI demonstrated good internal consistency
      (alpha=0.80), convergent validity (rho=0.51; p<.01), and test-retest reliability
      (intraclass correlation coefficient, 0.73; p<.01). As a result of the assessment
      of psychometric properties, driving tasks were categorized into the strategic
      (n=3), tactical (n=7), and operational (n=2) levels in the Michon model. The
      content validity of 11 symptoms (CVI >=80%) was established by the external
      panel. CONCLUSIONS: The NPDI was developed to assess the degree of perceived
      driving difficulty in the chronic whiplash population. Reliability and validity
      of the NPDI were ensured. The NPDI can be the entry point for discussions on
      driving difficulties between clinicians and patients with chronic WAD.

PMID- 23141369
TI  - [Foreword].

PMID- 23141370
TI  - Apoptosis in Blastocystis spp. is related to subtype.
AB  - Previous studies have shown that apoptosis-like features are observed in
      Blastocystis spp., an intestinal protozoan parasite, when exposed to the
      cytotoxic drug metronidazole (MTZ). This study reports that among the four
      subtypes of Blastocystis spp. investigated for rate of apoptosis when treated
      with MTZ, subtype 3 showed the highest significant increase after 72h of in vitro
      culture when treated with MTZ at 0.1mg/ml (79%; p<0.01) and 0.0001mg/ml (89%;
      p<0.001). The close correlation between viable cells and apoptotic cells for both
      dosages implies that the pathogenic potential of these isolates has been enhanced
      when treated with MTZ. This suggests that there is a mechanism in Blastocystis
      spp. that actually regulates the apoptotic process to produce higher number of
      viable cells when treated. Apoptosis may not just be programmed cell death but
      instead a mechanism to increase the number of viable cells to ensure survival
      during stressed conditions. The findings of the present study have an important
      contribution to influence chemotherapeutic approaches when developing drugs
      against the emerging Blastocystis spp. infections.

PMID- 23141371
TI  - Characteristics and surgical success of patients presenting for repair of
      obstetric fistula in western Kenya.
AB  - OBJECTIVE: To carry out a large-scale retrospective review of patients who had
      undergone surgical repair of obstetric fistula in Kenya to determine patient
      characteristics and determinants of successful surgical repair. METHODS: The
      patient records of 483 surgical repairs of obstetric fistula treated by a single
      surgeon (H.M.) between January 2005 and July 2010 at 3 medical centers in western
      Kenya were retrospectively reviewed. Descriptive and bivariate statistical
      analyses were performed. RESULTS: Young women with some primary or no education
      and prolonged labor at the time of first delivery were most highly correlated
      with obstetric fistula formation. Success of fistula closure was 86% for first
      time vesicovaginal fistula (VVF) repairs and 67% for first-time VVF combined with
      rectovaginal fistula (RVF) repairs. Among women who had previously attempted VVF
      or combined VVF/RVF repairs, 73% and 50% of fistulas, respectively, were repaired
      successfully. First-time repair was significantly associated with surgical
      success compared with patients with a history of previous repair attempts
      (P=0.027). CONCLUSION: Among Kenyan women presenting for fistula repair, fistula
      most was most highly correlated with a low level of education and prolonged
      labor. The findings are consistent with results reported from other countries in
      Sub-Saharan Africa.

PMID- 23141372
TI  - Early prediction of clinical and functional outcome in schizophrenia.
AB  - The objective of this paper was to investigate the prognostic and predictive
      value of a small panel of independent and clinically important factors based on
      symptom improvement, baseline cognitive impairment, and weight change during the
      early treatment phase. METHODS: The study sample was based on a double-blind, 6
      month continuation study of ziprasidone and olanzapine (N=94). We developed a
      parsimonious 6-month GAF prediction function using a logistic regression model,
      and evaluated its predictive accuracy and performance using bootstrap estimates
      of c-statistics and error in predicted probability. RESULTS: At up to 6 months of
      follow-up, 52 (55%) of all subjects treated with ziprasidone or olanzapine met
      the responder criterion of >=50% improvement in GAF. At Week 2 (acute phase), the
      majority of ziprasidone (75%) and olanzapine (70%) patients showed greater than
      25% improvement in the BPRS psychotic symptom subscale score. These early
      psychotic symptom responders (Week 2) showed significantly greater improvement in
      global functioning than early non-responders at all time points (Week 6 and Month
      6) (all p's<0.05), confirming early response as an indicator of continued
      responsiveness to treatment over at least 6 months. A multivariate prediction
      function based on baseline neurocognitive scores and GAF, early reduction of
      psychotic symptoms at 2 weeks, and percentage of weight change observed at 6
      weeks (All p's <0.05), showed statistically acceptable predictive performance
      (boostrap c-statistics=0.8598). CONCLUSIONS: Our findings suggest that a
      parsimonious model incorporating a psychotic symptom assessment score, baseline
      neurocognitive performance, and risk of weight gain can be developed for
      predicting patients' likelihood of achieving favorable, long-term treatment
      outcomes.

PMID- 23141374
TI  - Appearance of intracranial meningioma in FDG and 68Ga-DOTATOC PET/CT.

PMID- 23141373
TI  - Chronic tryptophan deprivation attenuates gating deficits induced by 5-HT(1A),
      but not 5-HT2 receptor activation.
AB  - The neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) exerts a multifaceted
      function in the modulation of information processing, through the activation of
      multiple receptor families. In particular, stimulation of 5-HT(1A) and 5-HT(2A)
      receptors leads to sensorimotor gating impairments and perceptual perturbations.
      Previous evidence has shown that chronic deprivation of L-tryptophan (TRP), the
      precursor of 5-HT, results in marked reductions of 5-HT brain levels, as well as
      neuroplastic alterations in 5-HT(1A) and 5-HT(2A) expression and/or signaling.
      Building on these premises, in the present study we tested whether a prolonged
      TRP deprivation may differentially impact the roles of these receptors in the
      regulation of the prepulse inhibition (PPI) of the acoustic startle reflex, a
      dependable index of gating. Male Sprague-Dawley rats were fed for 14 days with
      either a regimen with negligible TRP content (TR-) or the same diet supplemented
      of TRP (TR+). At the end of this schedule, rats were treated with the
      prototypical 5-HT(1A) receptor agonist 8-OH-DPAT (62.5-250 MUg/kg, subcutaneous,
      s.c.) or the 5-HT2 receptor agonist DOI (0.25-1 mg/kg, s.c.). Notably, the PPI
      deficits induced by 8-OH-DPAT in TR- rats were significantly milder than those
      observed in their TR+ counterparts; these effects were fully prevented by the 5
      HT(1A) antagonist WAY-100135 (10 mg/kg, intraperitoneal). Conversely, TRP
      deprivation did not affect the PPI-disrupting properties of DOI. These findings
      suggest that prolonged 5-HT depletion attenuates the influence of 5-HT(1A), but
      not 5-HT2 receptors on sensorimotor gating, confirming the distinct mechanisms of
      these two targets in PPI regulation.

PMID- 23141376
TI  - Design of a neutral three-dimensional electro-Fenton system with foam nickel as
      particle electrodes for wastewater treatment.
AB  - In this work, we demonstrate a novel three-dimensional electro-Fenton system (3D
      E-Fenton) for wastewater treatment with foam nickel, activated carbon fiber and
      Ti/RuO(2)-IrO(2) as the particle electrodes, the cathode, and the anode
      respectively. This 3D-E-Fenton system could exhibit much higher rhodamine B
      removal efficiency (99%) than the counterpart three-dimensional electrochemical
      system (33%) and E-Fenton system (19%) at neutral pH in 30 min. The degradation
      efficiency enhancement was attributed to much more hydroxyl radicals generated in
      the 3D-E-Fenton system because foam nickel particle electrodes could activate
      molecular oxygen to produce O(2)(-) via a single-electron transfer pathway to
      subsequently generate more H(2)O(2) and hydroxyl radicals. This is the first
      observation of molecular oxygen activation over the particle electrodes in the
      three-dimensional electrochemical system. These interesting findings could
      provide some new insight on the development of high efficient E-Fenton system for
      wastewater treatment at neutral pH.

PMID- 23141377
TI  - Sorption coefficients and molecular mechanisms of Pu, U, Np, Am and Tc to Fe
      (hydr)oxides: a review.
AB  - Pu, U, Np, Am and Tc are among the major risk drivers at nuclear waste management
      facilities throughout the world. Furthermore, uranium mining and milling
      operations have generated an enormous legacy of radioactively contaminated soils
      and groundwater. The sorption process of radionulcides onto ubiquitous Fe
      (hydr)oxides (FHOs; hematite, magnetite, goethite and ferrihydrite) is one of the
      most vital geochemical processes controlling the transport and fate of
      radionuclides and nuclear wastes in the subsurface zones. Meanwhile,
      understanding molecular-level chemical speciation of radionuclides onto FHOs is
      crucial to model their behavior in subsurface environments, and to develop new
      technologies for nuclear waste treatment and long-term remediation strategies for
      contaminated soils and groundwater. This review article aims (1) to provide risk
      or performance assessment modelers with macroscopic distribution coefficient
      (K(d)) data of Pu, U, Np, Am and Tc onto FHOs under different conditions (pH,
      radionuclide concentration, solution ion strength, sorbent loading, partial
      pressure of CO(2) (P CO(2)), equilibrium time) pertinent to environmental and
      engineered systems, and (2) to provide a microscopic or molecular-level
      understanding of the chemical speciation and sorption processes of these
      radionuclides to FHOs.

PMID- 23141378
TI  - Impact of water quality on removal of carbamazepine in natural waters by N-doped
      TiO2 photo-catalytic thin film surfaces.
AB  - Photocatalytic experiments on the pharmaceutical pollutant carbamazepine (CBZ)
      were conducted using sol-gel nitrogen-doped TiO(2)-coated glass slides under a
      solar simulator. CBZ was stable to photodegradation under direct solar
      irradiation. No CBZ sorption to the catalyst surface was observed, as further
      confirmed by surface characterization using X-ray photoelectron spectroscopic
      analysis of N-doped TiO(2) surfaces. When exposing the catalyst surface to
      natural organic matter (NOM), an excess amount of carbon was detected relative to
      controls, which is consistent with NOM remaining on the catalyst surface. The
      catalyst surface charge was negative at pH values from 4 to 10 and decreased with
      increasing pH, correlated with enhanced CBZ removal with increasing medium pH in
      the range of 5-9. A dissolved organic carbon concentration of 5mg/L resulted in
      ~20% reduction in CBZ removal, probably due to competitive inhibition of the
      photocatalytic degradation of CBZ. At alkalinity values corresponding to CaCO(3)
      addition at 100mg/L, an over 40% decrease in CBZ removal was observed. A 35%
      reduction in CBZ occurred in the presence of surface water compared to complete
      suppression of the photocatalytic process in wastewater effluent.

PMID- 23141379
TI  - Impacts of operating parameters on oxidation-reduction potential and pretreatment
      efficacy in the pretreatment of printing and dyeing wastewater by Fenton process.
AB  - An experiment was conducted in a batch reactor for a real printing and dyeing
      wastewater pretreatment using Fenton process in this study. The results showed
      that original pH, hydrogen peroxide concentration and ferrous sulfate
      concentration affected ORP value and pretreatment efficacy greatly. Under
      experimental conditions, the optimal original pH was 6.61, and the optimal
      hydrogen peroxide and ferrous sulfate concentrations were 1.50 and 0.75 gL(-1),
      respectively. The relationship among ORP, original pH, hydrogen peroxide
      concentration, ferrous sulfate concentration, and color (COD or BOD(5)/COD) was
      established, which would be instructive in on-line monitoring and control of
      Fenton process using ORP. In addition, the effects of wastewater temperature and
      oxidation time on pretreatment efficacy were also investigated. With an increase
      of temperature, color and COD removal efficiencies and BOD(5)/COD ratio
      increased, and they were in proportion to the exponent of temperature reciprocal.
      Similarly, color and COD removal efficiencies increased with increasing oxidation
      time, and both color and COD removal obeyed the first-order kinetics. The
      BOD(5)/COD ratio could be expressed by a second-degree polynomial with respect to
      oxidation time, and the best biodegradability of wastewater was present at the
      oxidation time of 6.10h.

PMID- 23141380
TI  - Modeling field-scale vertical movement of zinc and copper in a pig slurry-amended
      soil in Brazil.
AB  - Organic amendments often represent a source of trace metals (TMs) in soils, which
      may partly leach into the groundwater. The objectives of this study were (1) to
      validate Hydrus-2D for modeling the transport of Zn and Cu in an Alfisol amended
      with pig slurry (PS) by comparing numerical simulations and experimental field
      data, and (2) to model the next 50 years of TM movements under scenarios of
      suspended or continued PS amendments. First, between 2000 and 2008, we collected
      detailed Zn and Cu data from a soil profile in Santa Maria, Brazil. Two
      hypotheses about Zn and Cu reactivity with the solid phase were tested,
      considering physical, hydraulic, and chemical characteristics of six soil layers.
      Using a two-site sorption model with a sorption kinetic rate adjusted based on
      laboratory EDTA extractions, Hydrus simulations of the vertical TM transport were
      found to satisfactorily describe the soil Zn and Cu concentration profiles.
      Second, the long-term fate of Zn and Cu in the soil was assessed using the
      validated parameterized model. Numerical simulations showed that Zn and Cu did
      not present risks for groundwater pollution. However, future Cu accumulation in
      the surface soil layer would exceed the Brazilian threshold for agricultural
      soils.

PMID- 23141381
TI  - Use of the ages and stages questionnaire in young children who are deaf/hard of
      hearing as a screening for additional disabilities.
AB  - BACKGROUND: Children with sensorineural hearing loss have a high rate of
      additional disabilities beyond those expected by the impact of hearing loss on
      language and are identified later than children without hearing loss. Identifying
      these developmental delays and allowing earlier implementation of interventions
      specific to these concerns would improve care. AIMS: To determine whether the
      Ages and Stages Questionnaire (ASQ) can identify unmet needs or unidentified
      developmental delays among young children with bilateral sensorineural hearing
      loss. SUBJECTS: Fifty children with any degree of bilateral sensorineural hearing
      loss, 6months to 36months of age recruited from a tertiary referral center and
      regional early intervention programs for children who are deaf/hard of hearing.
      OUTCOME MEASURES: The ASQ and comprehensive developmental evaluations with the
      Revised Gesell Developmental Schedules. STUDY DESIGN: Sensitivities and
      specificities of the ASQ were calculated. RESULTS: While 32% of our population
      had a developmental delay outside the domain of communication, the ASQ had poor
      sensitivity on the overall score without the communication domain as well as for
      fine motor, cognitive, personal-social domains. It had good sensitivity for the
      domains of communication and gross motor skills and good specificity (ranging 83
      85%) on specific domains as well as for the overall score (70%). CONCLUSIONS: The
      ASQ does not provide an effective mean for identifying additional developmental
      concerns in young children with bilateral sensorineural hearing loss. Further
      studies are needed to determine how to identify additional disabilities in a
      timely manner among young children with hearing loss.

PMID- 23141382
TI  - Viral interference with antigen presentation: trapping TAP.
AB  - Following primary infection, herpesviruses persist for life in their hosts, even
      when vigorous anti-viral immunity has been induced. Failure of the host immune
      system to eliminate infected cells is facilitated by highly effective immune
      evasion strategies acquired by these herpesviruses during millions of years of co
      evolution with their hosts. Here, we review the mechanisms of action of viral
      gene products that lead to cytotoxic T cell evasion through interference with the
      function of the transporter associated with antigen processing, TAP. The viral
      TAP inhibitors impede transport of peptides from the cytosol into the ER lumen,
      thereby preventing peptide loading onto MHC class I complexes. Recent insights
      have revealed a pattern of functional convergent evolution. In every herpesvirus
      subfamily, inhibitors of TAP function have been identified that are,
      surprisingly, unrelated in genome location, structure, and mechanism of action.
      Recently, cowpox virus has also been found to encode a TAP inhibitor. Expanding
      our knowledge on how viruses perturb antigen presentation, in particular by
      targeting TAP, not only provides information on viral pathogenesis, but also
      reveals novel aspects of the cellular processes corrupted by these viruses,
      notably the translocation of peptides by the ATP-binding cassette (ABC)
      transporter TAP. As the various TAP inhibitors are anticipated to impede discrete
      conformational transitions it is expected that crystal structures of TAP
      inhibitor complexes will reveal valuable structural information on the actual
      mechanism of peptide translocation by TAP. Viral TAP inhibitors are also used for
      various (clinical) applications, for example, as effective tools in antigen
      presentation studies and as immunomodulators in immunotherapy for cancer,
      heterologous vaccination, and transplant protection.

PMID- 23141383
TI  - Risk disclosure and preclinical Alzheimer's disease clinical trial enrollment.
AB  - To identify the facilitators and barriers to preclinical Alzheimer's disease (AD)
      clinical trial recruitment, 50 cognitively normal participants were interviewed
      after being randomized to one of two hypothetical AD risk scenarios: (1) the
      general age-related risk for AD, or (2) being at 50% increased risk for AD.
      Participants provided uncued barriers and facilitators to the hypothetical
      decision of whether they would enroll. Thirteen themes of facilitators and five
      themes of barriers were identified. The most common barrier was fear related to
      taking study drug. Those randomized to being at increased risk for AD more
      frequently cited lowering personal risk as a facilitator (P = .01) and less
      frequently cited time as a barrier to enrollment (P = .02). These results suggest
      potential challenges to preclinical AD clinical trial recruitment and that
      disclosing risk information may enhance enrollment.

PMID- 23141385
TI  - The economics of mild cognitive impairment.
AB  - Individuals with amnestic mild cognitive impairment (MCI) are at elevated risk of
      developing Alzheimer's disease (AD). Although the economic burden of AD itself is
      well recognized, little is known about the direct and indirect costs associated
      with MCI before the onset of AD. Insufficient data on the economic impact of MCI
      as well as other gaps in the knowledge base (such as estimates of MCI progression
      rates and factors that drive MCI-related costs) present challenges to
      understanding the burden of MCI and to modeling the cost-effectiveness of
      potential MCI interventions. Initiating treatment and care management in the MCI
      phase could improve the health and well-being of patients and caregivers and
      possibly offset certain costs. Future economic analyses should incorporate new
      data, as they become available, from patient registries and linked administrative
      claims and electronic medical records to better characterize the cost
      consequences of MCI detection and management. Such analyses should help payers,
      providers, and policy makers make more informed decisions about the costs and
      benefits of new tests, treatments, and other management strategies for the
      condition.

PMID- 23141384
TI  - Intersite variability of CSF Alzheimer's disease biomarkers in clinical setting.
AB  - BACKGROUND: The assessment of total tau, phosphorylated tau (pTau-181) and
      amyloid beta (Abeta 1-42) concentrations in the cerebrospinal fluid (CSF) of
      subjects has been validated for the diagnosis of Alzheimer's disease (AD).
      Although these measurements have shown some variability, little is known about
      their intersite variability in clinical settings. METHODS: A total of 880
      subjects (AD, n = 515; non-AD, n = 365) from three French memory centers were
      included. Receiver-operating characteristic analyses were performed to
      computerized area under curves (AUCs) and optimal thresholds for each biomarker
      in the three centers. A test-retest study was performed in a group of 32 CSF
      samples by repeated blind analysis of the three biomarkers using the same
      immunoassay batches in the three centers. RESULTS: In the three centers, tau
      (AUC, 0.82-0.88) and pTau-181 (AUC, 0.83-0.89) outperformed Abeta 1-42 (AUC, 0.70
      -0.73) to discriminate subjects with AD from those without AD. An intersite
      variation of mean levels and cutoffs was observed for the three biomarkers. This
      variation was higher for Abeta 1-42 (range of cutoff, 368-582 pg/mL) than for tau
      (range of cutoff, 289-353 pg/mL). In a test-retest study, the mean
      interlaboratory coefficients of variation were 12.2% for Abeta 1-42, 11.3% for
      tau, and 11.5% for pTau-181. CONCLUSION: Intercenter variability of CSF
      biomarkers has been confirmed in a multisite cohort of subjects and can be
      improved in clinical settings. Efforts on harmonization of procedures should be
      encouraged to optimize the accuracy of CSF biomarkers in AD.

PMID- 23141386
TI  - Massed versus spaced visuospatial memory in cognitively healthy young and older
      adults.
AB  - BACKGROUND: The present study examined the effect of massed versus spaced
      learning trials on 24-hour delayed recall for a visuospatial learning task. To
      determine the utility of measuring the incremental benefit of spaced training as
      a cognitive assay that may be useful in early clinical trials, we used a within
      subject crossover design, with two small samples (typical sample sizes for phase
      I clinical trials). METHODS: Young adults and cognitively healthy older adults
      without significant physical, neurological, or psychiatric illness were trained
      on a visuospatial paired-associate learning task under a massed condition
      (learning trials were presented in immediate succession) and a spaced condition
      (learning trials were presented with 15-minute intertrial delays). RESULTS:
      Statistically significant differences between training conditions on the
      visuospatial task, such that young adult participants performed better on delayed
      recall after spaced training, were identified. Large effect sizes for young and
      older adults on this task suggest meaningful differences between training
      conditions, reflecting the expected "spacing effect." The role of amyloid
      aggregation was also considered for a subset of participants; as amyloid levels
      increased, the benefit of spaced training decreased, suggesting that the effect
      of this training paradigm is modulated by disease burden. CONCLUSIONS: The
      utility of this paradigm as a potential assay for phase I proof-of-concept
      trials, targeting molecular mechanisms that are central to the encoding and
      consolidation of new learning, is discussed.

PMID- 23141387
TI  - Use of two rapid influenza diagnostic tests, QuickNavi-Flu and QuickVue Influenza
      A+B, for rapid detection of pandemic influenza A (H1N1) 2009 viruses in Japanese
      pediatric outpatients over two consecutive seasons.
AB  - A prospective study of outpatient children conducted during 2 consecutive seasons
      (2009 and 2011) of pandemic influenza A (H1N1) 2009 virus determined the
      sensitivity of a chromatographic immunoassay test; real-time reverse
      transcription-polymerase chain reaction was the standard, and the test was 87.2%
      (117 patients in 2009) and 97.4% (114 patients in 2011) sensitive.

PMID- 23141388
TI  - [More understanding of pediatric allergic rhinitis].

PMID- 23141389
TI  - [Allergic Rhinitis and its Impact on Asthma (ARIA) achievements in 10 years and
      future needs].

PMID- 23141390
TI  - [Correlation between symptoms of pollen allergic rhinitis and pollen grain
      spreading in summer and autumn].
AB  - OBJECTIVE: To analyze the correlation between airborne pollen concentrations and
      symptoms in patients with pollen allergic rhinitis. METHODS: Durhum sampler was
      used to collect the pollen concentration and species from June to September in
      2011. The clinical skin prick test (SPT) data were analyzed. The patients with
      pollen allergic rhinitis were divided into pure pollen allergic rhinitis group
      (pollen group) and pollen combined perennial allergens allergic rhinitis group
      (combined group). Symptom scores of patients were assessed, and correlation
      between pollen concentration and onset of symptoms of patients were analyzed.
      SPSS 16.0 software was used to analyse the data. RESULTS: While the peak of
      Summer-Autumn pollen concentration appeared from August 20 to September 15, the
      major pollen included Artemisia L, Chenopodium album and Humulus scandens. The
      peak of pollen concentration in one day reached 638/1000 mm(2). The patients
      taken SPT from June to September accounted for 51.9% of the patients in whole
      year, among which SPT pollen positive patients were 1509, 60.7% of all SPT
      positive patients. The amount and rate of SPT positive patients showed
      significant correlation with pollen concentration(r value were 0.90 and 0.99,
      both P < 0.05). Onset of symptoms in two groups was correlated with pollen
      concentration in Summer-Autumn. Symptoms of cough in combined group showed more
      severe compared with patients with pollen group (t = 2.36, P < 0.05).
      CONCLUSIONS: Pollen concentration has a major effect on onset of symptoms of
      allergic rhinitis. Airborne pollen monitoring has important preventive and
      therapeutic significance on patients with allergic rhinitis.

PMID- 23141391
TI  - [Correlation of serum eosinophil cationic protein with the severity of allergic
      rhinitis in childhood].
AB  - OBJECTIVE: To investigate the relationships between the severity of childhood
      allergic rhinitis (AR) and the peripheral blood eosinophil count, serum
      eosinophil cationic protein (ECP), total IgE (tIgE), and allergen-specific IgE
      (sIgE) levels. METHODS: A total of 138 children with AR aged 3 to 17 (9.96 +/-
      3.78, x() +/- s) years old were enrolled in the study. All children had
      persistent AR sensitized to house dust mites with a clinical history of 3 months
      to 12 (4.21 +/- 2.72) years. The disease severity was evaluated using 10 cm
      visual analogue scale (VAS), and the serum levels of ECP, tIgE and sIgE were
      determined using an ImmunoCAP system. Statistical analysis was conducted with
      SPSS11.0 software. RESULTS: Among 138 children with AR, the VAS scores for global
      severity of rhinitis and nasal obstruction symptom were 5.32 +/- 2.16 and 4.78 +/
      2.45, respectively. Blood eosinophil count was 0.39 [0.24; 0.63] (M[P(25);
      P(75)]) *10(9)/ml. Serum levels of ECP and total IgE were 10.60 [3.26; 30.80]
      ug/L and (2.50 +/- 0.53) log kU/L, respectively. Serum levels of allergen-sIgE
      against Dermatophagoides pteronyssinus and Dermatophagoides farinae were
      58.20[24.75; > 100] kUA/L and 54.95 [24.55; > 100] kUA/L, respectively. The VAS
      scores of nasal obstruction symptom, but not global severity of rhinitis, were
      positively related to the duration of AR (r = 0.215, P = 0.011) and the levels of
      serum ECP (r = 0.196, P = 0.022) in bivariate correlation analysis. There was
      also a significant correlation between the serum ECP level and the blood
      eosinophil count (r = 0.295, P = 0.000). No relationships of blood eosinophil
      count, and serum tIgE and sIgE levels with global severity of rhinitis as well as
      nasal obstruction symptom were found (all P > 0.05). CONCLUSIONS: These results
      suggested that the severity of nasal obstruction was positively correlated with
      the duration of rhinitis and the levels of serum ECP in childhood persistent AR
      due to house dust mites, indicating the disease severity might be related to
      chronic inflammatory process.

PMID- 23141392
TI  - [Prevalence of allergic rhinitis and survey analysis of health service needs and
      utilization in Qingdao area].
AB  - OBJECTIVE: To investigate the need and utilization for health services in
      patients with allergic rhinitis in Qingdao area. METHODS: An investigation was
      conducted by the method of combining multi-stage sampling and cluster sampling.
      SPSS 13.0 software was used to analyse the data. RESULTS: Among Two thousand and
      four hundred questionnaires, two thousand and fifty-two questionnaires were
      available. The effective rate was 85.5%. The total two-week prevalence in male
      was 6.5%, while that in female was 6.2%. There was no significant difference
      between male and female (chi(2) = 0.103, P > 0.05). The total ratio of those who
      visited doctors was 1.7%. The ratio of those who visited doctors in the first two
      weeks was 26.7% (35/131). 49.0% of non-users of health service thought it was
      unnecessary to consult a doctor because of mild symptoms. In the investigation
      about the allergic rhinitis, 60.2% patients (1235/2052) confessed that they heard
      of allergic rhinitis, 30.0% patients (616/2052) thought of allergic rhinitis was
      common cold. CONCLUSIONS: The number of patients treated for allergic rhinitis
      was less than its prevalence. The primary reason for low attendance was that the
      majority of patients with mild symptoms thought it was no need to see a doctor.
      In order to improve the residents' health services utilization, medical education
      for allergic rhinitis is necessary.

PMID- 23141393
TI  - [Effect of combined use of sIL-5Ralpha and sIL-13Ralpha2 on VCAM-1 and IFN-gamma
      in allergic rhinitis rats].
AB  - OBJECTIVE: To investigate the effects of sIL-5Ralpha and sIL-13Ralpha2 on VCAM-1
      and IFN-gamma in allergic rhinitis rats. METHODS: A total of 50 Wistar rats were
      randomly divided into 5 groups: the normal group (group A), the allergic rhinitis
      model group (group B), the sIL-5Ralpha treatment group (group C), the sIL
      13Ralpha2 treatment group (group D), the combination of sIL-5Ralpha and sIL
      13Ralpha2 treatment group (group E or the combined treatment group). Rats in the
      latter 4 groups were sensitized with ovalbumin (OVA) and Al(OH)(3), and
      challenged with OVA to establish allergic rhinitis models, while rats in the
      normal group were treated with saline. Rats in the sIL-5Ralpha treatment group,
      the sIL-13Ralpha2 treatment group and the combined treatment group were absorbed
      on day 31 to day 38 once daily once nasal cavity with sIL-5Ralpha(100 ug), sIL
      13Ralpha2 (100 ug) and the combination of sIL-5Ralpha (100 ug) and sIL-13Ralpha2
      (100 ug) 30 min before challenged, while rats in the allergic rhinitis model
      group received PBS(50 ul). Then the levels of VCAM-1 and IFN-gamma in serum and
      nasal lavage fluid (NLF) were measured by ELISA. RESULTS: Compared with the
      normal group, the levels of VCAM-1 in the allergic rhinitis model group were
      higher, while IFN-gamma were lower (all P < 0.01). Compared with the allergic
      rhinitis model group, the sIL-5Ralpha treatment group, the sIL-13Ralpha2
      treatment group and the combined treatment group could effectively reduced serum
      and NLF VCAM-1 level [group E: (283.5 +/- 5.7) ug/L, (101.8 +/- 4.8) ug/L; group
      C: (311.5 +/- 12.6) ug/L, (133.9 +/- 5.8) ug/L; group D: (304.7 +/- 6.6) ug/L,
      (128.5 +/- 7.7) ug/L], and increased IFN-gamma level [group E: (874.7 +/- 9.6)
      pg/ml, (349.2 +/- 12.1) pg/ml; group C: (600.2 +/- 16.1) pg/ml, (195.5 +/- 16.1)
      pg/ml; group D: (577.9 +/- 9.6) pg/ml, (196.7 +/- 9.9) pg/ml ]; compared with
      single treatment, the combined treatment group also had significant differences(P
      < 0.01). CONCLUSIONS: Combined treatment with sIL-5Ralpha and sIL-13Ralpha2 to
      treat the allergic rhinitis rats can significantly reduce VCAM-1 levels in serum
      and NLF, and increase IFN-gamma levels, thus, to achieve the purpose of
      mitigation and treatment of allergic rhinitis.

PMID- 23141394
TI  - [Habituation of seasickness in adult during a long voyage].
AB  - OBJECTIVE: To observe the habituation of seasickness in non marine subjects
      during a long voyage. METHODS: A crew of 106 staffs of the Hospital Ship Ark
      Peace was included in this study. There were 59 male and 47 female with an age
      ranged from 23 to 53 years (mean 37.2 years). They all took part in the Mission
      Harmony 2011 for medical service in four countries around the Caribbean Sea.
      Questionnaires and visual analogue scales (VAS) were used to investigate the
      prevalence and degree of the seasickness in different periods. RESULTS: The
      prevalence of seasickness was 72.64% in the initial period of voyage. The
      prevalence and degree of seasickness in female and in staff with motion sickness
      history were higher and more severe than that in male and in staff without motion
      sickness history(P < 0.05). After two weeks, the prevalence and degree of
      seasickness decreased, which meant habituation of seasickness occurred. With the
      voyage going longer, the prevalence and degree of seasickness were further
      decreased, but the severe sea condition make the prevalence and degree of
      seasickness worse. The rate of habituation of seasickness was 62.33%, and the
      habituation rate of seasickness in male (76.92%) was higher than that in female
      (47.37%) (chi(2) = 7.161, P = 0.007). CONCLUSIONS: The habituation of the
      seasickness occurred after two weeks in a long voyage. Male are easier to get
      habituation of seasickness than female. The severe sea condition influences the
      prevalence and degree of seasickness.

PMID- 23141395
TI  - [Comparison of the basic characters of speech-evoked auditory brainstem response
      between school-age children and young adults].
AB  - OBJECTIVE: The aim of this study was to compare the basic characters of the
      speech-evoked auditory brainstem response (speech-ABR) between young adults and
      school-age children. METHODS: Speech-ABR of thirty eight normal hearing subjects
      including eighteen school-age children and twenty young adults were recorded. The
      speech syllable/da/as stimulus sound was transmitted to right ear by insertion
      the earphones in speech-ABR test. RESULTS: Response waves of speech-ABR in school
      age children were similar to those in young adults, which contained the onset
      response (peak V and A), the transition (peak C), the frequency following
      responses (peak D, E and F) and the offset response (peak O). Both the latency
      and amplitude showed no significant difference in all waves between young adults
      and school-age children, except the latency of wave O and amplitude of wave F.
      The latency of O wave in school-age children (47.80 +/- 0.38) ms were
      significantly shorter than that in adults (48.10 +/- 0.40) ms (t = 2.330,P =
      0.026). The amplitude of F wave in school-age children (-0.21 +/- 0.15) uV were
      significantly larger than that in adults (-0.12 +/- 0.08) uV (t = 2.146,P =
      0.043). CONCLUSION: Both the latency and amplitude of the speech ABR in school
      age children at 6 - 11 years old show the great similarity with the young adults,
      which indicate that the ability of speech processing of brainstem in children has
      completely reached maturity.

PMID- 23141396
TI  - [Longterm impact on swallowing quality-of-life after partial laryngectomy].
AB  - OBJECTIVE: To discuss the longterm quality-of-life related to swallowing function
      after different partial laryngectomy. METHODS: The worldwide known swallow
      quality-of-life questionnaire (SWAL-QOL, Hongkong, Chinese edition); was used in
      this research to evaluate the swallowing QOL on 96 postoperative patients who
      underwent different kinds of partial laryngectomy more than one year before. The
      patients were divided into 4 groups: supracricoid partial laryngectomy
      cricohyoidopexy (SCPL-CHP), supracricoid partial laryngectomy
      cricohyoidoepiglottopexy (SCPL-CHEP), horizontal supraglottic partial
      laryngectomy (horizontal PL), and vertical partial laryngectomy (vertical PL).
      RESULTS: A one-way MANOVA revealed a significant multivariate (the 11 scales of
      SWAL-QOL) main effect for groups (P < 0.01), and significant univariate main
      effects were obtained for groups in 9 scales out of 11 (P < 0.01). In all the 9
      scales vertical PL group acquired near full scores except the communication
      scale, and was significantly higher than the other 3 groups in many scales (P <
      0.05). CHP group acquired the worst scores of the 4 groups, showing significant
      differences in most of the 9 scales (P < 0.05). No significant difference was
      found between Horizontal PL and CHEP except in communication (P > 0.05). Patients
      with deglutition disorders (choke/cough) had a lower score in the social function
      scale. CONCLUSIONS: Swallowing quality-of-life of postoperative patients was
      deeply influenced even when more than one year had passed after surgery. Some of
      them felt deeply burdened by deglutition disorder. Patients after CHP proved to
      have a worst quality of life than the others, while vertical PL the best. The QOL
      between Horizontal PL and CHEP was shown to be almost the same. The influence
      over QOL from longterm dysphagia was multi-dimensional, containing the
      degeneration of social function.

PMID- 23141397
TI  - [Clinical classification and management of squamous intraepithelial lesions of
      the vocal cord].
AB  - OBJECTIVE: To discuss the clinical classification of the squamous intraepithelial
      lesions (SILs) of vocal cord and their outcomes after different therapeutic
      procedures. METHODS: Three hundred and forty-three patients with the SILs of
      vocal cord were enrolled. Based on the history of the diseases, macroscopic
      appearance by video rhino aryngoscopic, stroboscopic and microlaryngoscopic
      examination, and pathological findings, the correlation of clinical features,
      treatment modalities and treatment effect of the vocal cord SILs were discussed.
      RESULTS: According to the morphological characteristics, 343 patients were
      divided into four types. TypeI, leukoplakia combined with inflammation (n = 19);
      type II, leukoplakia combined with polyps by friction (n = 72); type III,
      leukoplakia combined with sulcus vocalis (n = 64); type IV, keratosis (n = 188).
      Patients with type I lesions were treated by medications. The vocal cord
      configuration and the voice of the patients in type I returned to normal after
      treatment. Patients with type II, III, IV lesions were treated by CO(2) laser.
      Type II were treated by subepithelial cordectomy, type III by mucosa slicing with
      dredging, type IV by sub ligament cordectomy or trans muscular cordectomy. The
      cure rate of patients with type II, III, IV lesions was 90.7% (294/324) after
      single surgery, the recurrent rate was 9.3% (30/324). Twenty-one patients
      (11.2%), all in type IV, developed carcinogenesis. Eight cases were diagnosed in
      the first surgery and 13 cases in the second. Among the 13 cases diagnosed in the
      second surgery, 2 cases had partial laryngectomy for the third surgery.
      CONCLUSIONS: Since the squamous intraepithelial lesions of vocal cord manifested
      differently, conservative treatment or CO(2) laser surgery should be used. In
      this way, a less invasive procedure, better recovery of the voice and less
      complication could be expected.

PMID- 23141398
TI  - [Lateral neck lymph node metastasis in cN0 papillary thyroid carcinoma].
AB  - OBJECTIVE: To study the pattern of lymph node spread in papillary thyroid
      carcinoma (PTC) with clinically negative node (cN0). METHODS: A total of 106
      patients with cN0 PTC who underwent total or subtotal thyroidectomy plus
      unilateral or bilateral lateral neck dissection (LND, level II-V or level I-V) at
      West China Hospital of Sichuan University between April 2004 and August 2010 were
      analyzed retrospectively. RESULTS: The lateral neck lymph node metastasis in cN0
      PTC was significantly associated with sex (male, P = 0.007), tumor stage (T3/T4,
      P = 0.006), tumor size (> 1 cm, P = 0.014) and the number of positive central
      lymph nodes (>= 2, P < 0.001), but not with age and multifocal tumor. Level III
      (47/116, 40.5%) was the most prevalent metastatic site, followed by level IV
      (41/116, 35.3%), level II (18/116, 15.5%) and level V (2/29, 6.9%). Of the cases
      with lymph node metastases in level III and IV, 89.8% (79/88) of primary thyroid
      tumors existed in the lower and middle sites of the thyroid lobes, while in the
      cases with lymph node metastases in level II, 77.8% (14/18) of primary thyroid
      tumors in the upper sites of the thyroid lobes, and 83.3% of cases with level II
      metastases were accompanied with level III metastases. Two cases with level V
      metastases were accompanied with metastases in levels II, III and IV.
      CONCLUSIONS: LND should be considered for cN0 PTC in male, with T3/T4 lesions and
      positive central lymph nodes >= 2, and the range of dissection should include
      level III and IV. Dissection of level II should be considered in cN0 PTC with
      primary tumor localized in the upper site of the thyroid lobe or with level III
      metastasis. Dissection of level V should be considered at present of metastases
      in level II, III, and IV. For cN0 PTC with tumor size < 1 cm, confined to the
      thyroid and without lymph node metastasis in the central compartment, LND is not
      recommended.

PMID- 23141399
TI  - [Evaluation of the function of autotransplanted parathyroid tissues].
AB  - OBJECTIVE: To evaluate the function autotransplanted parathyroid tissues in
      thyroid surgery. METHODS: The control group comprised 120 volunteers with normal
      parathyroid glands in whom serum parathyroid hormone (PTH) levels in blood
      samples taken from the bilateral elbow head veins. The experimental group
      comprised 34 patients in whom the parathyroid glands, which were mistakenly cut
      or could not be preserved during thyroid surgery because of ischemia, were
      fragmented and autografted into the brachioradialis muscle of the nondominant
      forearm. On the day of surgery and at 3 days, 7 days, and 2 months
      postoperatively, contrast imaging and detection of serum PTH levels were
      performed to evaluate the function of the transplanted parathyroid tissues.
      RESULTS: In the control group, the mean value of the difference between the
      bilateral brachiocephalic vein PTH levels was (1.19 +/- 0.98) ng/L (maximum 4.52
      ng/L). In this study, twice the maximum value (9.04 ng/L) was taken as the
      effective standard. Based on the 9.04 ng/L effective value, the effective number
      was 26 patients and the effective rate was 76.5% at 2 months postoperatively in
      the 34 patients of the experimental group. CONCLUSIONS: The autotransplanted
      parathyroid tissues showed their functions in most patients, therefore,
      parathyroid gland autotransplantation is an effective method of preserving
      function of parathyroid glands that are free or severely ischemic in thyroid
      surgery.

PMID- 23141400
TI  - [Antitumour efficacy of a novel oncolytic adenovirus Ad-TD-RFP for human
      nasopharyngeal carcinoma].
AB  - OBJECTIVE: To evaluate the antitumor efficacy of Ad-TD-RFP for human
      nasopharyngeal carcinoma cells (C666-1) in vitro and in vivo. METHODS: The
      oncolytic effects of Ad-TD-RFP and control virus dl11520 on C666-1 cells were
      determined by cytotoxicity assay (MTS assay). Viral replication of Ad-TD-RFP and
      dl11520 was detected at different time points (24 h, 48 h, 72 h and 96 h) by
      tissue culture infective dose (TCID(50)) in C666-1 cells implanted subcutaneously
      into the flank in each of BALB/c nude mice. The xenografts were injected
      intratumorally with Ad-TD-RFP or dl1520 to investigate their effects on tumor
      growth. RESULTS: The concentration for 50% of maximal effect (EC(50)) values of
      Ad-TD-RFP and dl1520 were (107.6 +/- 3.2) pt/cell and (174.1 +/- 4.0) pt/cell,
      respectively (t = 22.6, P < 0.001). The Ad-TD-RFP replication was 3-14 folds more
      than dl1520 replication at four time points (24 h, 48 h, 72 h and 96 h) in C666-1
      cells (t values were 33.6, 23.4, 20.8 and 17.3, respectively, P < 0.001). The
      average tumor volumes of PBS group, dl1520 group and Ad-TD-RFP group were (1765.5
      +/- 713.9) mm(3), (1036.9 +/- 623.8) mm(3), and (420.8 +/- 238.7) mm(3),
      respectively (F = 12.0, P < 0.05) on day 67 after treatment. CONCLUSIONS: The
      antitumour efficacy of the novel oncolytic adenovirus Ad-TD-RFP for human
      nasopharyngeal carcinoma C666-1 cells is superior to that of dl1520 in vitro and
      in vivo. The outcome of this study provides an experimental basis for the
      treatment of human nasopharyngeal carcinoma by viral gene therapy.

PMID- 23141401
TI  - [Short-term efficacy of semicircular canal occlusion in the treatment of
      intractable Meniere's disease].
AB  - OBJECTIVE: To investigate the short-term efficacy and safety of triple
      semicircular canal occlusion (TSCO) in the treatment of intractable Meniere's
      disease (MD), so as to provide an alternative surgical procedure for treating MD.
      METHODS: Seventeen patients, who had received standardized conservative treatment
      for at least one year with poor effect, underwent TSCO were retrospectively
      analyzed. Vertigo control and auditory function were evaluated. Pure tone
      audiometry, caloric test, and vestibular evoked myogenic potential (VEMP) were
      performed for evaluation of audiological and vestibular function. Postoperative
      follow-up period was 6 - 13 months, with an average of ten months. RESULTS:
      According to the preoperative staging of hearing, among the 17 patients, there
      were 2 cases in stage II (with an average hearing threshold of 25 - 40 dBHL) and
      15 in stage III (41 - 70 dBHL). No vertigo was found during the follow-up period,
      with 100% control rate of vertigo. During the same period, we had performed
      endolymphatic sac decompression operation in 25 MD patients. The control rate of
      vertigo was 72.0%. The vertigo control rate of TSCO was significantly higher than
      that of endolymphatic sac decompression operation (chi(2) = 3.87, P < 0.05).
      Three months after surgery, 12 patients showed no significant change in
      comparison to primary status, 5 patients presented with an mild increase in the
      average hearing threshold of less than 20 dBHL, with 29.4% of hearing loss rate.
      Post-operatively, all patients suffered from temporary vertigo and balance
      disorders. Vertigo was disappeared in all patients within 3 days, while, balance
      disorders were disappeared in 10 patients within 1 - 2 weeks after surgery, and
      in another 7 patients within 2 months, with an average recovery time of 12.6
      days. Three months after treatment, loss of semicircular canal function by
      caloric test was found in the operation side of all patients and no change in
      VEMP test was noted. All patients had no facial paralysis, cerebrospinal fluid
      leakage, and other complications. CONCLUSIONS: TSCO, which can reduce vertiginous
      symptoms in patients with intractable MD, represents an effective and safe
      therapy for this disorder. TSCO is expected to be used as an alternative
      procedure for the treatment of MD in selected patients suffering from moderate to
      severe hearing loss.

PMID- 23141402
TI  - [Investigation of skin prick test on 2707 patients with allergic rhinitis in
      Wuhan area].
AB  - OBJECTIVE: To investigate the distribution of common allergens in patients with
      allergic rhinitis (AR) from 2006 to 2010 in Wuhan area, and provide the objective
      evidence for the prevention and treatment of AR. METHODS: The medical records of
      skin prick test (SPT) performed on 2707 AR patients from 2006 to 2010 were
      retrospectively analysed, and the positive rate of different allergens and
      changing trends in this time were compared. SPSS 17.0 software was used to
      analyse the data. RESULTS: There were significant differences among the
      Dermatophagoides pteronyssinus positive rate (chi(2) = 12.11, P < 0.05) and
      Dermatophagoides farinae positive rate (chi(2) = 11.11, P < 0.05) in the past 5
      years. Meanwhile, there was an upward trend in the positive rate of dust mite,
      which the positive rate of Dermatophagoides pteronyssinus increased from 84.5% in
      2006 to 90.5% in 2010 (chi(2) = 6.88, P < 0.05), positive rate of
      Dermatophagoides farinae increased from 81.5% in 2006 to 89.0% in 2010 (chi(2) =
      9.68, P < 0.05); There were significant differences among the Mugwort and Ragweed
      positive rate of 5 years (chi(2) = 194.10, P < 0.05; chi(2) = 67.06, P < 0.05).
      There were significant differences among the mold I and mold II positive rate of
      5 years between (chi(2) = 18.95, P < 0.05; chi(2) = 36.62, P < 0.05). Meanwhile,
      there was an upward trend in the positive rate of mold and fluctuant trend in the
      positive rate of spring-pollen. CONCLUSIONS: Nearly five years, dust mites is
      still the most common allergens in AR patients, presenting upward trend; the
      positive rate of mold presenting upward trend; the positive rate of wormwood and
      guinea wood presenting downward trend; the positive rate of pollen presenting
      fluctuant trend.

PMID- 23141403
TI  - [A case of Wegener granulomatosis characterized by recurrent otitis media].

PMID- 23141404
TI  - [A case of lepromatous leprosy misdiagnosed of nasal sinusitis for long periods
      of time].

PMID- 23141405
TI  - [Diagnosis and treatment of 11 cases with multi-space infection in the face and
      neck].

PMID- 23141406
TI  - [Primary malignant melanoma of the maxillary sinus misdiagnosed as bleeding
      polyp].

PMID- 23141407
TI  - [Chondro-radionecrosis of larynx mimicking recurrence of laryngeal carcinoma-one
      case report].

PMID- 23141408
TI  - [Nasal septal perforation combined with chronic invasive fungal rhinosinusitis:
      three cases report].

PMID- 23141409
TI  - [Allergen-specific immunotherapy for pediatric allergic rhinitis].

PMID- 23141410
TI  - [Hypoglossal nerve stimulation in the treatment of obstructive sleep apnea
      hypopnea syndrome].

PMID- 23141411
TI  - [Evaluation of the psychological status in allergic rhinitis patients].

PMID- 23141412
TI  - Screening for rare variants in the coding region of ALS-associated genes at
      9p21.2 and 19p13.3.
AB  - Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease that
      causes progressive muscle weakness, eventually resulting in death because of
      respiratory failure. Genetic variants are thought to predispose to the disease. A
      recent, large, genome-wide association study identified 2 loci that increase
      susceptibility to ALS. These 2 loci on chromosomes 9 and 19 consist of 4 genes:
      UNC13a, IFNK, MOBKL2b, and C9ORF72. A hexanucleotide repeat expansion in the
      noncoding region of C9ORF72 was recently identified as the cause of chromosome 9
      linked ALS-FTD (frontotemporal dementia). In this study, our aim was to determine
      whether the coding regions of these genes harbor rare, nonsynonymous variants
      that play a role in ALS pathogenesis. In DNA from 1019 sporadic ALS patients and
      1103 control subjects of Dutch descent, we performed a mutation screening
      analysis in the coding region of these 4 genes by resequencing the exons. A total
      of 16 amino acid-changing rare variations were identified, 11 in UNC13a and 5 on
      chromosome 9. Some of these were unique to ALS, but were detected in a single
      patient. None of the genes showed significant enrichment of rare variants in the
      coding sequence. Rare variants in the coding region of UNC13a, IFNK, MOBKL2b, and
      C9ORF72 are unlikely to be a genetic cause of ALS.

PMID- 23141413
TI  - Oxidative stress induces DNA demethylation and histone acetylation in SH-SY5Y
      cells: potential epigenetic mechanisms in gene transcription in Abeta production.
AB  - Overwhelming evidence has suggested that enhanced oxidative stress is involved in
      the pathogenesis and/or progression of Alzheimer's disease (AD). Amyloid-beta
      (Abeta) that composes senile plaques plays a causal role in AD, and its abnormal
      deposition in brains is the typical neuropathologic hallmark of AD. Recent
      studies have suggested that epigenetic mechanisms play an important role in the
      initiation and development of AD. In the present study, we investigated the
      epigenetic mechanisms, such as DNA methylation and histone acetylation, involved
      in the transcription of AD-related genes with Abeta production under oxidative
      stress. Human neuroblastoma SH-SY5Y cells were treated with hydrogen peroxide
      (H(2)O(2)) and used as the cell model. The intracellular Abeta level was
      significantly increased in H(2)O(2)-treated SH-SY5Y cells. The expression of
      amyloid-beta precursor protein and beta-site amyloid-beta precursor protein
      cleaving enzyme 1 was upregulated by demethylation in the gene promoters
      associated with the reduction of methyltransferases. Meanwhile, H(2)O(2) induced
      the upregulation of histone acetyltransferases p300/cAMP-response element binding
      protein (p300/CBP) and downregulation of histone deacetylases. DNA
      hypomethylation induced by DNA methyltransferase inhibitor could activate the DNA
      binding activity of transcription factor nuclear factor-kappaB, whereas no
      significant effect was observed on specific protein 1. DNA binding activities of
      nuclear factor-kappaB and specific protein 1 were activated by histone
      hyperacetylation induced by histone deacetylase inhibitor. These findings
      suggested that oxidative stress resulted in an imbalance between DNA methylation
      and demethylation and histone acetylation and deacetylation associated with the
      activation of transcription factors, leading to the AD-related gene transcription
      in the Abeta overproduction. This could be a potential mechanism for oxidative
      stress response, which might contribute to the pathogenesis and development of
      AD.

PMID- 23141414
TI  - A novel phosphorylation site mutation in profilin 1 revealed in a large screen of
      US, Nordic, and German amyotrophic lateral sclerosis/frontotemporal dementia
      cohorts.
AB  - Profilin 1 is a central regulator of actin dynamics. Mutations in the gene
      profilin 1 (PFN1) have very recently been shown to be the cause of a subgroup of
      amyotrophic lateral sclerosis (ALS). Here, we performed a large screen of US,
      Nordic, and German familial and sporadic ALS and frontotemporal dementia (FTLD)
      patients for PFN1 mutations to get further insight into the spectrum and
      pathogenic relevance of this gene for the complete ALS/FTLD continuum. Four
      hundred twelve familial and 260 sporadic ALS cases and 16 ALS/FTLD cases from
      Germany, the Nordic countries, and the United States were screened for PFN1
      mutations. Phenotypes of patients carrying PFN1 mutations were studied. In a
      German ALS family we identified the novel heterozygous PFN1 mutation p.Thr109Met,
      which was absent in controls. This novel mutation abrogates a phosphorylation
      site in profilin 1. The recently described p.Gln117Gly sequence variant was found
      in another familial ALS patient from the United States. The ALS patients with
      mutations in PFN1 displayed spinal onset motor neuron disease without overt
      cognitive involvement. PFN1 mutations were absent in patients with motor neuron
      disease and dementia, and in patients with only FTLD. We provide further evidence
      that PFN1 mutations can cause ALS as a Mendelian dominant trait. Patients
      carrying PFN1 mutations reported so far represent the "classic" ALS end of the
      ALS-FTLD spectrum. The novel p.Thr109Met mutation provides additional proof-of
      principle that mutant proteins involved in the regulation of cytoskeletal
      dynamics can cause motor neuron degeneration. Moreover, this new mutation
      suggests that fine-tuning of actin polymerization by phosphorylation of profilin
      1 might be necessary for motor neuron survival.

PMID- 23141415
TI  - Prevalence of HIV among women entering labor who accepted or declined voluntary
      counseling and testing.
AB  - OBJECTIVE: To assess whether there was a difference in HIV seroprevalence between
      eligible women who declined and those who agreed to participate in a study of
      voluntary counseling and testing among women entering labor with unknown HIV
      status in South Africa. METHODS: Anonymous cord blood specimens were collected-as
      dried blood spots-from all women approached for participation in a cluster
      randomized trial. No patient identifiers were included on the cord blood
      specimens. The dried blood spots were analyzed for HIV antibody via enzyme
      immunoassay and western blotting. RESULTS: Of 7238 women screened for study
      participation, 1041 (14.4%) had undocumented HIV status; of these women, 542 were
      eligible for inclusion and 343 enrolled. Based on 513 evaluable samples, the
      overall seroprevalence was 13.3% (95% confidence interval [CI], 10.4-16.5), which
      was similar to the 13.1% (95% CI, 9.7-17.2) seroprevalence among the 343 enrolled
      women. CONCLUSION: Seroprevalence among eligible women was similar to that among
      enrolled women, which indicates that study participation did not select for a
      group with an HIV seroprevalence substantially different from that among women
      who declined to enroll.

PMID- 23141416
TI  - Ehrlichia canis in dogs in a semiarid region of Northeastern Brazil: serology,
      molecular detection and associated factors.
AB  - This study investigated infection by Ehrlichia spp. agents by PCR,
      immunofluorescence assay test (IFAT), and by Giemsa-stained blood smears in 108
      dogs from a semiarid region of the state of Paraiba, Northeastern Brazil. Seventy
      five (69.4%) of the 108 dogs were found to be seropositive to Ehrlichia canis,
      while only four dogs (3.7%) were positive in real-time PCR for E. canis. In six
      dogs (5.6%) E. canis-like morulae were observed in monocytes. Animals that stayed
      in environment whose floor was dried dirt, and dogs whose owners reported low
      frequency of cleaning the dog environment had higher (P<0.05) PCR positivity for
      E. canis. Increasing seropositivity was found in older dogs (P=0.012). This study
      provides the first molecular detection of E. canis in the semiarid region of
      Northeastern Brazil.

PMID- 23141417
TI  - Effect of long-term feed restriction on the health status and welfare of a robust
      horse breed, the Shetland pony (Equus ferus caballus).
AB  - Outdoor group housing is increasingly recognized as an appropriate housing system
      for domesticated horses. The objective of this study was therefore to investigate
      the effect of potential feed shortage in semi-natural horse keeping systems in
      winter on animal health and welfare. In 10 female Shetland ponies blood
      concentrations (NEFA, total protein (TP), total bilirubin (TB), beta
      hydroxybutyrate (BHB) and thyroxine (T4)), body mass and the body condition score
      (BCS) were monitored for 7 months including a 4 months period of feed restriction
      in five of the 10 ponies. Restrictively fed animals lost 18.4+/-2.99% of their
      body mass and the BCS decreased by 2.2+/-0.8 points (BCS scale: 0=emaciated,
      5=obese). Feed restriction led to a continuous increase in TB (P<0.001) and NEFA
      (P<0.01) concentrations compared to control ponies. The TP and BHB values only
      differed at the end of the trial with lower concentrations in restricted fed
      mares (P<0.05). Feed restriction had no effect on thyroxine concentrations. TB
      concentrations in the feed restricted group were out of the reference range
      during the entire feeding trial. The increased NEFA concentrations in feed
      restricted compared to control ponies suggest that fat was mobilized. The BCS, as
      well as plasma NEFA and TB concentrations were good indicators for a rapid
      detection of possible health problems caused by undernourishment in horses when
      kept under semi-natural conditions. In contrast, blood parameters of the control
      animals were within the reference ranges, suggesting that a year round outdoor
      housing with additional feed supply is an adequate housing system for a robust
      horse breed like the Shetland pony.

PMID- 23141418
TI  - Optimization and structure-activity relationships of a series of potent
      inhibitors of methicillin-resistant Staphylococcus aureus (MRSA) pyruvate kinase
      as novel antimicrobial agents.
AB  - A novel series of hydrazones were synthesized and evaluated as inhibitors of
      methicillin-resistant Staphylococcus aureus (MRSA) pyruvate kinase (PK). PK has
      been identified as one of the most highly connected 'hub proteins' in MRSA. PK
      has been shown to be critical for bacterial survival which makes it a potential
      target for development of novel antibiotics and the high degree of connectivity
      implies it should be very sensitive to mutations and thus less able to develop
      resistance. PK is not unique to bacteria and thus a critical requirement for such
      a PK inhibitor would be that it does not inhibit the homologous human enzyme(s)
      at therapeutic concentrations. Several MRSA PK inhibitors (including 8d) were
      identified using in silico screening combined with enzyme assays and were found
      to be selective for bacterial enzyme compared to four human PK isoforms (M1, M2,
      R and L). However these lead compounds did not show significant inhibitory
      activity for MRSA growth presumably due to poor bacterial cell penetration.
      Structure-activity relationship (SAR) studies were carried out on 8d and led us
      to discover more potent compounds with enzyme inhibiting activities in the low
      nanomolar range and some were found to effectively inhibit bacteria growth in
      culture with minimum inhibitory concentrations (MIC) as low as 1 MUg/mL. These
      inhibitors bind in two elongated flat clefts found at the minor interfaces in the
      homo-tetrameric enzyme complex and the observed SAR is in keeping with the size
      and electronic constraints of these binding sites. Access to the corresponding
      sites in the human enzyme is blocked.

PMID- 23141419
TI  - Does sex affect 30-day mortality in Staphylococcus aureus bacteremia?
AB  - BACKGROUND: Sex-related differences in complications and mortality of infection
      were examined with conflicting results. Further studies are required to bring new
      light in this topic in Staphylococcus aureus infections. OBJECTIVE: We examined
      the outcomes of S. aureus infection in men and in women and whether sex-related
      differences were explained by underlying disorders, severity of disease, or
      clinical management. METHODS: This cohort study was conducted in a single center
      between 1988 and 2007. Patients with clinically significant S. aureus bacteremia
      were included. We compared 30-day all-cause mortality in men and women. We used
      multivariable logistic regression analysis to test whether sex was independently
      associated with mortality. RESULTS: One thousand ninety-three patients were
      identified with S. aureus bacteremia. All-cause mortality at day 30 was 39.3%
      (508 of 1293 patients): 44.8% (238 of 531 patients) in women and 35.4% (270 of
      762 patients) in men (P < 0.01). In a multivariate analysis, female sex was
      associated with higher mortality (odds ratio = 1.63; 95% CI, 1.07-2.47). The
      excess mortality in women was not explained by differences in demographic
      characteristic factors, background conditions, infection severity and management,
      or septic complications. CONCLUSIONS: We found that women with S. aureus
      bacteremia had a greater risk of 30-day all-cause mortality than men, even when
      adjusting for other risk factors. However, we failed to explain this excess of
      mortality.

PMID- 23141420
TI  - Clear cell carcinoma of the base of the tongue.

PMID- 23141421
TI  - Dynamic transmission of West Nile virus across the United States-Mexican border.
AB  - Confirmed clinical and veterinary cases of West Nile virus (WNV) infection in
      Mexico remain restricted to northern Mexico, supporting a unidirectional
      transmission model from the US into Mexico. Full-length genomic sequencing of
      nine WNV isolates obtained from Culex spp. mosquito pools in El Paso, Texas (n=7)
      and Cuidad Juarez, Mexico (n=2) from 2005 to 2010 demonstrates the co-circulation
      of three independent genetic groups, two of which belong to the southwestern
      (SW/WN03) genotype and the other to the North American (NA/WN02) genotype. These
      results indicate ongoing dynamic circulation of WNV between the United States and
      Mexico.

PMID- 23141422
TI  - Bone properties by nanoindentation in mild and severe osteogenesis imperfecta.
AB  - BACKGROUND: Osteogenesis imperfecta is a heterogeneous genetic disorder
      characterized by bone fragility. Previous research suggests that impaired
      collagen network and abnormal mineralization affect bone tissue properties,
      however, little data is yet available to describe bone material properties in
      individuals with this disorder. Bone material properties have not been
      characterized in individuals with the most common form of osteogenesis
      imperfecta, type I. METHODS: Bone tissue elastic modulus and hardness were
      measured by nanoindentation in eleven osteotomy specimens that were harvested
      from children with osteogenesis imperfecta during routine surgeries. These
      properties were compared between osteogenesis imperfecta types I (mild, n=6) and
      III (severe, n=5), as well as between interstitial and osteonal microstructural
      regions using linear mixed model analysis. FINDINGS: Disease severity type had a
      small but statistically significant effect on modulus (7%, P=0.02) and hardness
      (8%, P<0.01). Individuals with osteogenesis imperfecta type I had higher modulus
      and hardness than did those with type III. Overall, mean modulus and hardness
      values were 13% greater in interstitial lamellar bone regions than in osteonal
      regions (P<0.001). INTERPRETATION: The current study presents the first dataset
      describing bone material properties in individuals with the most common form of
      osteogenesis imperfecta, i.e., type I. Results indicate that intrinsic bone
      tissue properties are affected by phenotype. Knowledge of the material properties
      of bones in osteogenesis imperfecta will contribute to the ability to develop
      models to assist in predicting fracture risk.

PMID- 23141423
TI  - Analysis of robotic performance times to improve operative efficiency.
AB  - STUDY OBJECTIVE: To estimate the efficiency of procedural steps in robotic
      sacrocolpopexy and concomitant hysterectomy. DESIGN: Retrospective study
      (Canadian Task Force classification II-2). SETTING: University hospital.
      PATIENTS: One hundred forty-seven patients who underwent robotic-assisted
      procedures from November 2007 through December 2010. INTERVENTIONS: Robotic
      assisted sacrocolpopexy. Sixty patients (40.8%) underwent concomitant
      hysterectomy; 37 (25.2%), mid-urethral sling placement; and 7 (4.8%), concomitant
      colporrhaphy. MEASUREMENTS AND MAIN RESULTS: Comparison of the first 20
      procedures with the subsequent 127 demonstrated that there was considerable
      improvement in time of cuff closure (p = .04); sacral dissection (p = .004);
      anterior (p = .006), posterior, (p = .003), and sacral (p = .003) mesh
      attachment; peritoneal closure (p < .001); total docked time (p = .02); and total
      incision time (p < .001). CONCLUSION: Robotic efficiency improves over a short
      learning period, with greatest differences in intracorporeal suturing and overall
      times. Identifying these steps may aid surgeons and learners in improving overall
      efficiency and establishing benchmarks for performance.

PMID- 23141424
TI  - Equality of employment opportunities for nurses at the point of qualification: an
      exploratory study.
AB  - BACKGROUND: Securing employment after qualification is of utmost importance to
      newly qualified nurses to consolidate knowledge and skills. The factors that
      influence success in gaining this first post are not known. OBJECTIVES: The study
      aimed to describe the first post gained after qualification in terms of setting,
      nature of employment contract and geographical distribution and explore the
      relationship between a range of factors (including ethnicity) and employment at
      the point of qualification. DESIGN: An exploratory study using structured
      questionnaires and secondary analysis of data routinely collected by the
      universities about students and their progress during their course. SETTINGS: The
      study was conducted in eight universities within a large, multicultural city in
      the UK as part of the 'Readiness for Work' research programme. PARTICIPANTS:
      Eight hundred and four newly qualified nurses who had successfully completed a
      diploma or degree from one of the universities; a response rate of 77%
      representing 49% of all graduating students in the study population. METHODS:
      Data were collected by self-completed semi-structured questionnaires administered
      to students at the time of qualification and at three months post-qualification.
      Routinely collected data from the universities were also collected. RESULTS:
      Fifty two percent of participants had been offered a job at the point of
      qualification (85% of those who had applied and been interviewed). Of these, 99%
      had been offered a nursing post, 88% in the city studied, 67% in the healthcare
      setting where they had completed a course placement. 44% felt "confident" and 32%
      "very confident" about their employment prospects. Predictors of employment
      success included ethnicity, specialty of nursing and university attended.
      Predictors of confidence and preparedness for job seeking included ethnicity,
      nursing specialty, gender and grade of degree. Newly qualified nurses from non
      White/British ethnic groups were less likely to get a job and feel confident
      about and prepared for job seeking. CONCLUSIONS: This study has demonstrated that
      ethnicity does lead to employment disadvantage for newly qualified nurses. This
      is an important contribution towards recognizing and describing the evidence so
      that appropriate responses and interventions can be developed. It is important
      that universities and healthcare institutions work closely together to support
      students at this important time in their nursing career.

PMID- 23141425
TI  - EGCG inhibits CTGF expression via blocking NF-kappaB activation in cardiac
      fibroblast.
AB  - Connective tissue growth factor (CTGF) has been reported to play an important
      role in tissue fibrosis and presents a promising therapeutic target for fibrotic
      diseases. In heart, inappropriate increase in level of CTGF promotes fibroblast
      proliferation and extracellular matrix (ECM) accumulation, thereby exacerbating
      cardiac hypertrophy and subsequent failure. Epigallocatechin-3-gallate (EGCG),
      the major polyphenol found in green tea, possesses multiple protective effects on
      the cardiovascular system including cardiac fibrosis. However, the molecular
      mechanism by which EGCG exerts its anti-fibrotic effects has not been well
      investigated. In this study, we found that EGCG could significantly reduce
      collagen synthesis, fibronectin (FN) expression and cell proliferation in rat
      cardiac fibroblasts stimulated with angiotensinII (AngII). It also ameliorated
      cardiac fibrosis in rats submitted to abdominal aortic constriction (AAC).
      Moreover, EGCG attenuated the excessive expression of CTGF induced by AAC or
      AngII, and reduced the nuclear translocation of NF-kappaB p65 subunit and
      degradation of IkappaB-alpha. Subsequently, we demonstrated that in cardiac
      fibroblasts NF-kappaB inhibition could suppress AngII-induced CTGF expression.
      Taken together, these findings provide the first evidence that the effect of EGCG
      against cardiac fibrosis may be attributed to its inhibition on NF-kappaB
      activation and subsequent CTGF overexpression, suggesting the therapeutic
      potential of EGCG on the prevention of cardiac remodeling in patients with
      pressure overload hypertrophy.

PMID- 23141426
TI  - Chinese medicine formula "Weikang Keli" induces autophagic cell death on human
      gastric cancer cell line SGC-7901.
AB  - Weikang Keli (constitutes of Root of Codonopsis pilosula, Rhizoma Atractylodis
      Macrocephalae, Rhizoma Curcumae Aeruginosae, Rhizoma Pinelliae, Actinidia
      chinensis Planch, and Rhodiola rosea) is a well known Chinese herbal formula for
      gastric cancer therapy in clinical treatment. However, the detailed molecular
      mechanisms involved are still not fully understood. In this study, we found that
      Weikang Keli could induce patterns of autophagy in SGC-7901 cells, including
      intracellular vacuole formation, microtubule-associated protein 1 light chain 3
      (LC3) conversion. Hoechst 33258 staining and Western blot analysis of apoptosis
      related proteins showed that WK induced SGC-7901 cell death was not through
      apoptosis. In vivo study also revealed that i.g. administration of Weikang Keli
      once a day for 25 days could significantly reduce tumor volumes by about 50%.
      Collectively, the current data indicated that Weikang Keli induced gastric cancer
      cell death by autophagy effects.

PMID- 23141427
TI  - Relieving visceral hyperalgesia effect of Kangtai capsule and its potential
      mechanisms via modulating the 5-HT and NO level in vivo.
AB  - Kangtai capsule (KT) is one type of traditional Chinese medicine preparation
      derived from the proved recipe, which was frequently applied as an effective
      clinical treatment of IBS. However, there still lack the reasonable and all-round
      analytical approach and the scientific studies on its underlying mechanisms.
      Therefore, our study aimed to develop the novel method for evaluating its quality
      as well as to interpret the potential mechanisms. In our study, high performance
      liquid chromatography (HPLC) fingerprint was applied to provide a chemical
      profile of KT. The neonatal maternal separation (NMS) on Sprague-Dawley pups was
      employed to evaluate the therapeutic effect of KT by virtue of various parameters
      including visceral hyperalgesia, serum nitric oxide (NO) level, and tissue 5
      hydroxytryptamine (5-HT) level. Consequently, a chromatographic condition, which
      was carried at 30 degrees C with a flow rate of 0.5 ml/min on AQUA 3MU C18 column
      with mobile phase of acetonitrile and water-phosphoric acid (100:0.1, v/v), was
      established to give a common fingerprint chromatography under 254 nm with a
      similarity index of 0.963 within ten batches of KT samples. On the NMS model, KT
      markedly elevated the pain threshold of NMS rats. Furthermore, KT at three doses
      significantly decreased 5-HT content from distal colon of visceral hyperalgesia
      rats induced by NMS, while the significant decrease of 5-HT content in serum was
      only observed in the group with KT at high dose. However, compared with that in
      NMS rats without KT, there was no apparent difference of 5-HT level from brain
      issue in the rats with various doses. Besides, KT could substantially elevate the
      concentration of NO in the serum. The results showed our study developed the
      simple, rapid, accurate, reproducible qualitative and quantitative analysis by
      HPLC fingerprint for the quality control for KT. Data from the pharmacological
      investigation suggested that the curative effect of KT to the visceral
      hypersensitivity may be concerned with the level of 5-HT and NO in vivo,
      promising its potential in irritable bowel syndrome treatment.

PMID- 23141428
TI  - alpha-band oscillations, attention, and controlled access to stored information.
AB  - Alpha-band oscillations are the dominant oscillations in the human brain and
      recent evidence suggests that they have an inhibitory function. Nonetheless,
      there is little doubt that alpha-band oscillations also play an active role in
      information processing. In this article, I suggest that alpha-band oscillations
      have two roles (inhibition and timing) that are closely linked to two fundamental
      functions of attention (suppression and selection), which enable controlled
      knowledge access and semantic orientation (the ability to be consciously oriented
      in time, space, and context). As such, alpha-band oscillations reflect one of the
      most basic cognitive processes and can also be shown to play a key role in the
      coalescence of brain activity in different frequencies.

PMID- 23141430
TI  - Factors influencing embryo transfer success in alpacas: a retrospective study.
AB  - Embryo transfer offers great advantages to South American camelid farmers to
      reach their breeding goals but the technology still plays a relatively minor role
      in comparison to other domestic farm animals like cattle. The aim of the present
      study was to analyse a data set of 5547 single or multiple ovulation embryo
      transfers performed in commercial alpaca farms in Australia to determine the
      factors that influence number and quality of embryos produced, embryo transfer
      success (percentage of crias born) and gestation length following transfer.
      Logistic binary regression identified the variables day of flushing after mating,
      embryo diameter, embryo quality, day of transfer after GnRH, and the age of the
      recipient to have significant impact on the outcome measure embryo transfer
      success. Transfer of smaller embryos or lower quality embryos resulted in
      decreased transfer success rates. Optimal days for obtaining embryos from donors
      were Days 8 and 9 after mating, optimal days for transfer into recipients were
      Days 7 and 8 after GnRH treatment. Age (>15 years) and body condition of
      recipients <2 also lowered transfer success rates, while the summer heat had no
      adverse impact. However, season did influence gestation length, while cria gender
      did not. In conclusion, results from the analysis of this very large dataset can
      underpin new recommendations to improve embryo transfer success in alpacas.

PMID- 23141429
TI  - Memory-guided attention: control from multiple memory systems.
AB  - Attention is strongly influenced by both external stimuli and internal goals.
      However, this useful dichotomy does not readily capture the ubiquitous and often
      automatic contribution of past experience stored in memory. We review recent
      evidence about how multiple memory systems control attention, consider how such
      interactions are manifested in the brain, and highlight how this framework for
      'memory-guided attention' might help systematize previous findings and guide
      future research.

PMID- 23141431
TI  - Metformin enhances the action of insulin on porcine granulosa-lutein cells in
      vitro.
AB  - Metformin is an oral antidiabetic drug extensively used to treat the polycystic
      ovary syndrome in women. Metformin increases insulin-stimulated glucose uptake
      and has direct effects on ovarian steroidogenesis in humans. However, the
      molecular mechanisms of metformin' action on the ovary are not clear. To
      investigate the effects of this drug on the insulin-signaling pathway in porcine
      granulosa cells as an alternative model for human research, we examined the mRNA
      expressions of porcine insulin receptor (INSR), insulin-like growth factor-1
      receptor (IGF-1R), insulin receptor substrate-1 (IRS-1), and the protein activity
      (activation and phosphorylation) of downstream targets including Raf, mitogen
      activated protein kinase (MEK)1/2, extracellular signal regulated kinase (ERK),
      phosphoinositide-dependent 1 kinase (PDK1), mammalian target of rapamycin (TOR),
      p70, and nuclear factor-kappaB (NF-kappaB) in a primary culture system consisting
      of porcine granulosa-lutein cells (pGLs) incubated with 10(-5)M metformin and/or
      100ng/ml insulin for 24h in a serum-free medium. We also investigated the
      luciferase activity of transcription factors activator protein-1 (AP-1) and NF
      kappaB. Metformin with insulin significantly increased mRNA expressions of INSR,
      IGF-1R, and IRS-1, while metformin alone had no significant effect. And metformin
      with insulin had the significant effect on the protein activity (activation and
      phosphorylation) of downstream targets of INSR signaling pathway. Metformin with
      insulin significantly elicited an induction of luciferase activity in the
      transfection of AP-1 and NF-kappaBreporter, while metformin alone did not. In
      conclusion, we examined the activity of metformin and insulin on pGLS in vitro
      and metformin enhanced the action of insulin on the intracellular signaling
      pathways. These results suggest that metformin could change the function of
      ovarian granulosa cells.

PMID- 23141432
TI  - Driver distraction and performance effects of highway logo sign design.
AB  - Driver distraction and safety concerns have been identified for new highway logo
      sign configurations. This study assessed driver perception of logo signs and
      distraction under nine-panel, overflow-combination, or standard six-panel
      formats. A nine-panel sign has nine business panels within a single sign; a six
      panel sign has six panels within a sign; an overflow-combination consists of a
      standard six-panel sign and a six-panel sign displaying two different services
      (e.g., food and gas). In this study, twenty-four participants searched for target
      food business logos while driving in a high-fidelity driving simulation under
      each signage condition. Gas and lodging signs were also displayed along the road
      in conventional six-panel formats. Dependent variables included signal detection,
      visual attention allocation, and vehicle control measures. Experiment results
      showed nine-panel signs drew greater visual attention and produced lower average
      speed than overflow-combination signs, and produced a lower speeding percentage
      compared to six-panel signs. However, there was no evidence the new
      configurations (nine-panel and overflow) caused substantive performance changes
      with safety implications. This study suggested the use of nine-panel and overflow
      combination logo signs may be suitable for interchanges where there are more than
      six qualifying businesses in a category in terms of driver performance and
      safety.

PMID- 23141433
TI  - A pox upon your house.
AB  - Herpes zoster ophthalmicus (HZO) is a common viral infectious disorder affecting
      the ophthalmic division of the trigeminal nerve. A small subset of HZO patients
      present with the ophthalmic symptoms, but without an accompanied rash, a
      condition described as Herpes zoster sine herpete. Although HZO is well known to
      be associated with other central nervous system abnormalities, encephalitis and
      cerebral infarction are atypical and uncommon. We report an unusual case of
      presumed unilateral Herpes zoster ophthalmicus sine herpete that presented with
      trigeminal pain and uveitis and then progressed to encephalitis and bilateral
      cerebral infarctions despite treatment with acyclovir and corticosteroids. The
      diagnosis of HZV was confirmed by polymerase chain reaction testing on the
      cerebrospinal fluid. 

PMID- 23141434
TI  - Effect of environmental manganese exposure on verbal learning and memory in
      Mexican children.
AB  - Manganese (Mn) is an essential metal, but in excess it becomes neurotoxic.
      Children's developing nervous system may be especially vulnerable to the
      neurotoxic effects of overexposure to this metal. The aim of this study was to
      assess the effect of Mn exposure on verbal memory and learning in 7- to 11-year
      old children. We tested 79 children living in the Molango Mn-mining district and
      95 children from a non-exposed community in the same State of Mexico. The
      Children's Auditory Verbal Learning Test (CAVLT) was administered. Blood and hair
      samples were obtained to determine Mn concentrations using atomic absorption
      spectrophotometry. CAVLT performance was compared between the two groups and
      multilevel regression models were constructed to estimate the association between
      biomarkers of Mn exposure and the CAVLT scores. The exposed group presented
      higher hair and blood Mn (p<0.001) than the non-exposed group (median 12.6 vs.
      0.6MUg/g, 9.5vs. 8.0MUg/L respectively), as well as lower scores (p<0.001) for
      all the CAVLT subscales. Hair Mn was inversely associated with most CAVLT
      subscales, mainly those evaluating long-term memory and learning (beta=-0.47, 95%
      CI -0.84, -0.09). Blood Mn levels showed a negative but non-significant
      association with the CAVLT scores. These results suggest that Mn exposure has a
      negative effect on children's memory and learning abilities.

PMID- 23141435
TI  - [Promote a healthy development of tinnitus research in China].

PMID- 23141436
TI  - [Interpretation of Chinese 2012 tinnitus experts consensus].

PMID- 23141437
TI  - [Some mistakes in the diagnosis and treatment of tinnitus].

PMID- 23141438
TI  - [Study on reliability and validity of the Tinnitus Evaluation Questionnaire].
AB  - OBJECTIVE: To investigate the value of the Tinnitus Evaluation Questionnaire
      (TEQ) in clinical application. METHODS: Cronbach's alpha coefficient was used to
      examine the reliability of the TEQ internal consistency. Examined the re-measured
      reliability by the correlation coefficient by two doctors' 1 - 3 hours interval
      questionnaires' scores. And inspected criteria validity according to the
      correlation coefficient of the TEQ and Tinnitus Handicap Inventory (THI).
      RESULTS: In the 202 tinnitus patients, the TEQ Cronbach's alpha coefficient was
      0.76 and re-measured reliability was 0.938. The THI correlation coefficient was
      0.769. Among which, 99 patients feel tinnitus alleviated obviously after the
      treatment, the TEQ scores were significantly lower than that before the treatment
      (t = 21.42, P < 0.001). CONCLUSIONS: The TEQ reflects the severity of tinnitus
      completely, and has preferable reliability and validity. The characteristics are
      concise, practical and exact. It is worthy of clinical application.

PMID- 23141439
TI  - [Influence of visual and auditory masking on the brain glucose metabolism in an
      idiopathic tinnitus patient].
AB  - OBJECTIVE: To study the influence of the audio-visual block (AB) on the brain
      glucose metabolism of idiopathic tinnitus patients. METHODS: The brain positron
      emission tomography (PET) test was performed on one chronic idiopathic tinnitus
      patient under audio-visual block and non-block (NB) conditions respectively. The
      visual analysis and statistical parameter mapping (SPM) analysis were both used
      to detect the brain glucose metabolism difference under AB and NB conditions.
      RESULTS: Under NB conditions, significant hyperactivity was detected at auditory
      and visual cortex on both sides of the brain. However, this phenomenon was not
      shown under AB conditions. Instead, a hyperactivity of brain was presented in the
      left Wernicke's area. CONCLUSIONS: The generation of chronic idiopathic tinnitus
      probably has no relationship with the auditory cortex abnormity. Wernicke's area
      might be involved in the central perception of tinnitus.

PMID- 23141440
TI  - [Relationship between the tinnitus frequency and the effects of medication and
      the prognosis in patients with chronic subjective tinnitus].
AB  - OBJECTIVE: To investigate the influence of tinnitus frequency on medication and
      prognosis in patients with chronic subjective tinnitus. METHODS: Seventy-two
      patients (Ninety-three ears) diagnosed as chronic subjective tinnitus were
      studied from October 2010 to March 2011. All cases were divided into low
      frequency(twenty-three ears), medium frequency(fourteen ears) and high frequency
      (fifty-six ears) according to tinnitus matching test. All cases were treated with
      microcirculation promotion and steroid therapy (5% glucose 250 ml + ginkgo biloba
      extract 87.5 mg + dexamethasone 10 mg intravenous drip). Curative effect was
      evaluated and the factors of prognosis were analyzed after three weeks. RESULTS:
      After medication, results were acquired as follows: recovery in 0 ear (0%),
      excellent in 0 ear (0%), effective in 18 ears (19.4%), invalid in 75 ear (80.6%).
      The effective percentage was 39.1%, 35.7% and 7.1%, respectively. There was
      significant difference between these groups, but no significant difference
      between low frequency and medium frequency. Logistic regression analysis showed
      that the difference of frequency was significant prognostic factors for
      medication. CONCLUSIONS: Microcirculation promotion and steroid therapy had a
      poor treatment effect in patients with chronic subjective tinnitus. The prognosis
      of chronic low-medium frequency tinnitus was better than chronic high frequency
      tinnitus. The difference of frequency retained significant influence on effects
      and prognosis of medication.

PMID- 23141442
TI  - [Treatment of infantile subglottic hemangioma with oral propranolol].
AB  - OBJECTIVE: To observe the efficacy of oral Propranolol in the treatment of
      infantile subglottic hemangioma. METHODS: Eleven children (6 females and 5 males)
      with a median age at onset of treatment being 4 months were included in this
      study. Propranolol was given after laryngoscopy and a CT scan with contrast of
      the trachea confirming the presence of a subglottic hemangioma. The starting dose
      of Propranolol was 0.5 mg/kg per day, given in 2 or 3 divided doses. Heart rate
      and blood glucose were monitored during the treatment. If no side effects
      occurred, the dose was increased to 1 mg/kg per day at the third day and to 2
      mg/kg per day at the sixth day. Treatment was continued at home after 10 days of
      inpatient treatment and the children were reevaluated monthly. RESULTS: After 24 
      48 hours of treatment, all of the children had improvement in their airway
      obstruction which was confirmed by fibro-laryngoscopy. The diameter of the
      subglottic stenosis from the hemangioma decreased from 3.9 - 5.0 mm to 1.5 - 2.0
      mm,and the color was also lighter than before. In 3 children with cutaneous
      hemangioma, there was also significant improvement in the cutaneous lesions after
      treatment, with the color becoming lighter. There were no significant ECG, blood
      pressure or blood biochemical changes during the treatment. Two of the children
      had hypoglycemia at the first dose, but improved after blood transfusion and
      changing their diet. In five children, the treatment was stopped after 6 to 11
      months when the obstructive symptoms improved. None of the children in this group
      had any evidence of recurrence. In the 5 children who stopped treatment, the
      obstructing mass in the subglottis was less than 10% of the diameter. CONCLUSION:
      Oral propranolol is a safe and effective treatment for infantile subglottic
      hemangioma. It may be used as a first-line therapeutic modality.

PMID- 23141441
TI  - [Analysis of follow-up outcomes of endoscopic modified Lothrop procedure].
AB  - OBJECTIVE: To sum up the follow-up outcomes of endoscopic modified Lothrop
      procedure (EMLP) and retrospectively analyze the indications, methods and
      prognostic factors of EMLP. METHODS: The collected data of 73 cases who received
      EMLP with frontal sinus diseases were analyzed in this paper. The mean age was
      45.6 (ranging from 14 to 72 years). There were 52 males and 21 females. Only
      patients with follow-up time greater or equal to 6 months were included.
      Paranasal sinus CT scan was adopted for all cases and MRI for tumor patients. All
      patients were followed under endoscope. RESULTS: There were 21 inverted papilloma
      in the frontal sinus, 16 chronic sinusitis with asthma, 12 frontal sinusitis, 9
      chronic sinusitis with or without polyps, 7 osteoma of the frontal sinus, 4
      frontal mucocele, 3 allergic fungal sinusitis and 1 congenital encephalocele.
      Sixty-one cases had prior surgical history (1.8 times on the average). Their mean
      follow-up was 25.0 months, (ranging from 6 to 122 months). At the end of follow
      up, 44 cases (60.3%) had well opened frontal drainage pathway. Twenty-five
      (34.2%) was re-stenosed and 4 (5.5%) closed. Seven cases (9.6%) underwent
      revision surgeries. There were no surgical complications. CONCLUSIONS: EMLP is an
      effective and salvage procedure in dealing with tumor of frontal sinus and
      recurrent frontal sinusitis. Combined with medical treatment, EMLP will have a
      better results for chronic sinusitis with or without polyps and asthma. The
      degree of diseases, mucosal loss, anatomic variability and prior surgeries are
      important prognostic factors.

PMID- 23141443
TI  - [Study of radioactivities in parathyroid and near tissues during radioguided
      parathyroidectomy].
AB  - OBJECTIVE: To determine the radioactivities in parathyroid and near tissues
      during radioguided parathyroidectomy in patients with hyperparathyroidism and the
      utility of parathyroidectomy in patients with negative (99m)Tc-sestamibi scans.
      METHODS: Between August 2010 and August 2011, 21 patients underwent radioguided
      parathyroidectomy for hyperthyroidism. The levels of parathyroid hormone (PTH)
      and serum calcium before and after surgery were detected respectively. In vivo
      and ex vivo radioactivities in parathyroid and near tissues were examined.
      According to the radioactivity in parathyroid, the patients were divided into two
      groups, positive group and negative group. All data was descriptively analyzed
      and underwent a t test and an analysis of variance. RESULTS: In all patients both
      PTH and calcium levels decreased significantly after parathyroidectomy when
      compared to those before surgery (t' = 17.71 and t = 10.00, respectively, P <
      0.001). In vivo and ex vivo radioactivities in enlarged parathyroid glands were
      higher than those in thyroid and fat tissue (F = 75.25 and 37.81, respectively, P
      < 0.001). In vivo and ex vivo radioactivities of the enlarged parathyroid with
      negative sestamibi scans were significantly greater than background
      radioactivity. CONCLUSIONS: There are significant differences in (99m)Tc
      sestamibi radioactivities among enlarged parathyroid glands, thyroid glands and
      fat tissues. This radioguided technique is helpful to identify abnormal
      parathyroid gland in patients with hyperparathyroidism during parathyroidectomy.

PMID- 23141444
TI  - [Microstructural changes of olfactory mucosa in rat model with acute
      rhinosinusitis leading to olfactory dysfunction].
AB  - OBJECTIVE: To observe the microstructural changes of olfactory mucosa in rat
      model with acute rhinosinusitis leading to olfactory dysfunction, and to provide
      foundation for further exploration of corresponding mechanism. METHODS: On the
      basis of prior successfully established rat model of acute rhinosinusitis through
      inoculation with Streptococcus pneumoniae and with the help of merocel strips,
      one hundred healthy SD rats were randomly divided into experimental group (80)
      and control group (20). After inoculation, every 20 rats in the experimental
      groups were sacrificed in first week, second week, third week and fourth week
      respectively; and all rats in the control group were sacrificed in first week
      after the inoculation. Before the rats were sacrificed, the method called "buffed
      food pellet test, BFPT" was adopted, which was advanced by professor Nathan, to
      measure the rats' olfaction,and the time of every rat spending in finding out the
      food pellet was recorded and analyzed. BFPT showed that the rats in experimental
      group spent (402.9 +/- 9.3), (453.7 +/- 7.3), (351.9 +/- 8.9), (278.7 +/- 8.1) s
      respectively in searching the food pellet, which were more than the rats in the
      control group [(178.3 +/- 6.6) s]. Then the olfactory mucosa was collected under
      anatomic microscope from all the rats to make frozen section and detect the
      changes of mature olfactory receptor neurons (ORN) and olfactory ensheathing
      cells (OEC) by immunofluorescence technique. RESULTS: The reduction of ORN in
      various degrees could be detected in the tissue samples of olfactory mucosa among
      all the rats in experimental group, with a tendency to become thinner in the
      thickness of epithelial lamina during the inflammation developing course. This
      kind of pathology was most marked in the second week and it gradually developed
      into the stage showing the lesion being the feeblest in the forth week following
      the beginning of modeling. Although the number of olfactory ensheathing cells
      appeared reduction in the first week following the beginning of modeling as
      well,it came to increase from the second week before olfactory receptor neurons
      and almost completely recovered to normal in the fourth week. In addition, some
      olfactory ensheathing cells could be detected in the tissue samples of olfactory
      mucosa among all the rats in experimental group. CONCLUSIONS: Both mature
      olfactory sensory neurons and olfactory ensheathing cells appeared to reduction
      when sinonasal mucosa taken place acute rhinosinusitis. But the number of
      olfactory ensheathing cells increased faster than olfactory sensory neurons. In
      addition, some olfactory ensheathing cells could be detected in the olfactory
      epithelium.

PMID- 23141445
TI  - [EGCG regulates TGF-beta1-induced epithelial mesenchymal transition in squamous
      cell carcinoma of head and neck].
AB  - OBJECTIVE: To study the effect and molecular mechanism of epigallocatechin-3
      gallate (EGCG) on epithelial-mesenchymal transition (EMT) in vitro induced by
      human recombinant TGF-beta1 protein in squamous cell carcinoma of the head and
      neck. METHODS: EMT morphological changes of Tu686 cells were observed after
      sequential treatment of 5 ng/ml TGF-beta1 and 20 umol/L EGCG. Tu686 cells were
      collected after the treatment of 5 ng/ml TGF-beta1 for 24 h and EGCG with
      different concentrations (0, 10, 20, 30 umol/L) for another 24 h or 20 umol/L
      EGCG treatment for different time phase (6, 12, 24 h). Then RT-PCR and Western
      blot were applied to detect mRNA and protein expression level of epithelial cell
      marker E-cadherin, mesenchymal cell marker Vimentin and Smad7, an inhibit
      molecule of TGF-beta1 mediated pathway in Tu686 cells. RESULTS: TGF-beta1
      successfully induced characterized EMT morphological and molecular changes in
      Tu686 cells, in which expression of E-cadherin decreased, Vimentin increased and
      Smad7 declined. However, EGCG could reverse the TGF-beta1 mediated process of EMT
      by downregulating the expression of Vimentin and upregulating the expression of E
      cadherin and Smad7. CONCLUSION: EGCG significantly inhibits TGF-beta1-mediated
      EMT inTu686 cell lines of SCCHN, which maybe associated with the upregulated
      expression of Smad7, an inhibitor in TGF-beta1 signaling pathway.

PMID- 23141446
TI  - [Inhibition of human laryngeal carcinoma growth by gene therapy and epigenetic
      therapy].
AB  - OBJECTIVE: To observe the effects of gene therapy and epigenetic therapy on the
      tumor growth of laryngeal carcinoma and the underlying mechanisms. METHODS: The
      animal model of human laryngeal carcinoma was established by the subcutaneous
      inoculation of Hep-2 cells at the right armpit of BALB/c nu/nu mice. The tumor
      bearing mice were randomized into 4 groups, p53 therapy group(rAd-p53),
      epigenetic therapy group(5-aza-dC), combination therapy group (rAd-p53+5-aza-dC)
      and control group. The gene and protein expressions of molecular markers p53 and
      E-cadherin were detected by FQ-PCR and immunohistochemistry. RESULTS: By the day
      20 of the treatments, the mean tumor volumes were(106.09 +/- 24.40)mm(3) in p53
      therapy group, (166.55 +/- 40.11) mm(3) in epigenetic therapy group, (126.11 +/-
      22.49) mm(3) in combination therapy group,and (252.83 +/- 54.09) mm(3) in control
      group. Both gene therapy (F = 37.30, P < 0.05) and epigenetic therapy (F = 4.79,
      P < 0.05) inhibited the growth of xenografted tumors, with an interaction effect
      (F = 22.01, P < 0.05) between the two groups. The integral optical density value
      of p53 protein expression of p53 therapy group (628.07 +/- 95.16) was
      significantly higher than that of combination therapy group (494.76 +/- 100.22),
      (t = 8.72, P < 0.05). The integral optical density values of E-cadherin protein
      expression were 558.89 +/- 97.58 in p53 therapy group, 380.41 +/- 90.60 in
      epigenetic therapy group, 494.76 +/- 102.88 in combination therapy group,and
      162.60 +/- 40.38 in control group respectively, indicating the enhancements of E
      cadherin protein expression by gene therapy (F = 45.24, P < 0.05) or epigenetic
      therapy(F = 5.73, P < 0.05)and the existence of interaction effect (F = 21.82, P
      < 0.05) between gene therapy and epigenetic therapy. The expression levels of p53
      gene were 4.43 +/- 0.12 in p53 therapy group, 1.06 +/- 0.11 in epigenetic therapy
      group, 3.51 +/- 0.10 in combination therapy group,and 1.09 +/- 0.11 in control
      group, respectively, showing an interaction effect between gene therapy and
      epigenetic therapy (F = 298.11, P < 0.05). The expression levels of E-cadherin
      gene were 4.50 +/- 0.34 in p53 therapy group, 2.02 +/- 0.16 in epigenetic therapy
      group, 2.99 +/- 0.12 in combination therapy group, and 1.00 +/- 0.11 in control
      group, respectively. The expression of E-cadherin gene was enhanced by gene
      therapy (F = 329.12, P < 0.05)or epigenetic therapy(F = 88.57, P < 0.05), with an
      interaction effect between the two therapies (F = 122.17, P < 0.05). CONCLUSIONS:
      Xenografted tumors of human laryngeal carcinoma cells are inhibited by gene
      therapy, the epigenetic therapy and the combination therapy. The gene therapy was
      significantly better than the epigenetic therapy or the combination therapy.
      There might be antagonistic effect between p53 and 5-aza-dC.

PMID- 23141447
TI  - [Analysis of the hereditary etiology of 336 patients with non-syndromic
      sensorineural hearing loss from Ningxia Hui Autonomous Region of China].
AB  - OBJECTIVE: To investigate the molecular genetic causes and their characteristics
      of deafness in Ningxia province, we established screening of three common
      hereditary deafness genes in 336 deaf and hard-of-hearing patients in this
      district. METHODS: Peripheral blood samples were obtained from a total of 336
      patients with non-syndromic sensorineural hearing loss in parts of special
      education schools in Ningxia province to extract genomic DNA. The mitochondrial
      DNA 12S rRNA m.1555A > G mutation was screened by PCR Alw26I digestion and
      sequence analysis PCR and direct sequencing were used to analyze the coding
      region of GJB2 and exons 8 and 19 of SLC26A4. Statistical analysis was performed
      by using SPSS 11.0 software. Frequencies of different GJB2 or SLC26A4 mutations
      were compared between Han and Hui people. RESULTS: Among these 336 patients,
      seven cases (2.08%, 7/336) were found to carry mtDNA 12S rRNA m.1555A > G
      homozygous mutation, 45 cases (13.39%) were caused by GJB2 mutations and 28 cases
      (8.33%) had two mutated alleles (homozygote and compound heterozygote) of
      SLC26A4. In detail, 16.67% (56/336) patients carried GJB2 mutations including 11
      single mutant carriers. The allele frequency of c.235delC and c.299_300delAT were
      9.52% (64/672) and 2.68% (18/672), respectively, making up 81.19% (82/101) of all
      pathogenic mutated alleles for GJB2. The single mutant allele carriers of SLC26A4
      is 32, and two types (c.919-2A > G and c.2168A > G) accounted for 95.29% (24/27)
      mutations, totally. We also found that statistically significant differences in
      c.919-2A > G and c.2168A > G frequencies between Han and Hui people (c.919-2A >
      G, chi(2) = 8.229, P = 0.004; c.2168A > G, chi(2) = 5.277, P = 0.022). However,
      there was no statistically significant difference in GJB2 mutation between Han
      and Hui people. CONCLUSIONS: GJB2 mutation was a primary cause for non-syndromic
      sensorineural hearing loss in Ningxia province, and c.235delC was the most common
      mutant forms of GJB2. c.919-2A > G and c.2168A > G were common mutant forms of
      SLC26A4, their frequencies were also statistically significant differences
      between Han and Hui people.

PMID- 23141448
TI  - [Clinical observation on the origin of antrochoanal polyp].
AB  - OBJECTIVE: To explore the origin and etiopathogenesis of antrochoanal polyp (ACP)
      based on the clinical data. METHODS: Twenty-six patients with ACP were included
      in the study. All the ACP patients were documented by preoperative endoscopy and
      computer tomographic (CT) scans. All patients were treated under endonasal
      endoscopic surgery. The relationship between polyp in middle meatus and lesions
      in the antrum was observed during the surgery. Following surgical removal, the
      polyps and lesions in the antrum were studied under macroscopy and microscopy.
      RESULTS: Among 26 cases with ACP, 17 cases were confirmed by preoperative
      endoscopic examination that polyp originating from antrum ostium, 19 cases showed
      intimate relationship between the polyp and antrum lesions in CT scan, and 23
      cases were found that the polyp originating from the antrum cyst. The pedicle of
      polyp connected the cyst through autrum ostium, and the polyp existed as a part
      of capsule wall. CONCLUSION: Based on the data obtained, it is tempting to
      suggest that the ACP mainly develops from antral cyst, an increase in pressure in
      cyst forced capsule wall to herniate to middle meatus through the antral ostium,
      and the continuous herniation and hyperplasy leading to the formation of ACP.

PMID- 23141449
TI  - [Clinical analysis of therapeutic effect of CT guided percutaneous catheter
      drainage in the treatment of parapharyngeal abscess].

PMID- 23141450
TI  - [One case with bilateral huge internal carotid artery aneurysm was misdiagnosed
      as bilateral tonsil hypertrophy].

PMID- 23141451
TI  - [One case of Zenker's diverticulum misdiagnosed as thyroid nodules on
      ultrasonography].

PMID- 23141452
TI  - [One case of tonsillar metastasis of lung cancer found in palpation].

PMID- 23141453
TI  - [Report of case with laryngeal nerve palsy and tracheal cartilage necrosis after
      thyroid microwave ablation].

PMID- 23141454
TI  - [Manifestations of dermatomyositis in otorhinolaryngology].

PMID- 23141455
TI  - [Nose and base of the skull invasive osteoblastoma in one case].

PMID- 23141456
TI  - [A case report: osteoma of the nasal septum].

PMID- 23141457
TI  - [Advanced parotid carcinoma metastasize to aryepiglottic fold: one case report].

PMID- 23141458
TI  - [Research progress of transcranial magnetic stimulation treatment for tinnitus].

PMID- 23141459
TI  - [Cochlear implant and tinnitus].

PMID- 23141460
TI  - [Research progress in diagnosis and treatment of tinnitus].

PMID- 23141461
TI  - Late onset of symptoms in an atypical patient with the cblJ inborn error of
      vitamin B12 metabolism: diagnosis and novel mutation revealed by exome
      sequencing.
AB  - Inborn errors of vitamin B(12) (cobalamin) metabolism are characterized by
      decreased production of active cobalamin cofactors and subsequent deficiencies in
      the activities of methionine synthase and methylmalonyl-CoA mutase. With the
      recent discovery of the cblJ defect in two patients with phenotypes mimicking the
      cblF defect, there are nine genes known to be involved in cobalamin metabolism.
      The new defect is caused by mutations in the ABCD4 gene, encoding an ABC
      transporter. At the moment, there is no clear distinction between the cblJ and
      cblF defects either clinically or biochemically, and both defects result in
      blocks in the transport of cobalamin from the lysosome to the cytoplasm. A
      patient was diagnosed with hyperhomocysteinemia and methylmalonic aciduria at the
      age of 8 years. Incorporations of both [(14)C]propionate and
      [(14)C]methyltetrahydrofolate in cultured fibroblasts were within reference
      ranges and thus too high to allow for complementation analysis. We observed
      decreased synthesis of both adenosylcobalamin and methylcobalamin and
      accumulation of unmetabolized cyanocobalamin. Exome sequencing was performed to
      identify causative mutation(s) and Sanger re-sequencing was performed to validate
      segregation of mutation in the family. By this approach, a homozygous mutation,
      c.423C>G, in the ABCD4 gene was identified. Here, we report the successful
      application of exome sequencing for diagnosis of a rare inborn error of vitamin
      B(12) metabolism in a patient whose unusual presentation precluded diagnosis
      using standard biochemical and genetic approaches. The patient represents only
      the third known patient with the cblJ disorder.

PMID- 23141462
TI  - Identification of mutations in the NUCB2/nesfatin gene in children with severe
      obesity.
AB  - Nesfatin-1 is the N-terminal fragment of nucleobindin-2 (NUCB2) that was
      identified as a novel satiety molecule in rodents. The protein is reported to
      exert anorexigenic effects and appears to play an important role in hypothalamic
      pathways regulating energy homeostasis and food intake. In this study, we
      hypothesized that mutations in the nesfatin encoding gene NUCB2 might cause
      obesity in humans. Therefore, we screened the entire coding region of the NUCB2
      gene for mutations in a population of 471 obese children and adolescents.
      Mutation analysis of NUCB2 identified a total of seven sequence variants of which
      four were previously reported as polymorphisms. The remaining three variants
      included ex9+6G>C, L125H and K178X and were found in 3 unrelated individuals in
      the obese population only (0.6%). Biochemical experiments including ELISA and
      western blot were performed on plasma samples of the obese patient carrying the
      nonsense mutation K178X. However, neither NUCB2/nesfatin-1 immunoreactive plasma
      levels of the patient, nor expression of full length NUCB2 differed significantly
      from matched obese control individuals. In conclusion, we have identified the
      first genetic variants in the NUCB2 gene in obese individuals, although further
      functional characterization will be essential to verify disease causality of the
      mutations.

PMID- 23141463
TI  - Maternal uniparental disomy of chromosome 2 in a patient with a DGUOK mutation
      associated with hepatocerebral mitochondrial DNA depletion syndrome.
AB  - We report maternal uniparental disomy of chromosome 2 (matUPD2) in a 9-month-old
      girl presenting with hepatocerebral mitochondrial DNA depletion syndrome. This
      patient was homozygous for the c.352C>T (p.Arg118Cys) mutation in DGUOK gene. The
      proband's mother was heterozygous for the mutation was absent in DNA of the
      father. For proband, the absence of paternal contribution at the DGUOK locus
      prompted us to exclude intragenic DGUOK deletion of the paternal allele with
      Multiplex ligation-dependent probe amplification (MLPA) analysis. We also
      excluded non-paternity by studying various markers at different loci. Then we
      performed an analysis of copy number variations and absence of heterozygosity
      (AOH) on the proband DNA using high resolution oligonucleotides microarray.
      Several large regions of AOH with no copy number change were detected on
      chromosome 2 and one of these AOH regions encompassed DGUOK gene. These results
      were confirmed with haplotype analysis using polymorphic markers. Informative
      SNPs and microsatellites markers spanning the whole chromosome 2 showed a matUPD2
      with heterodisomy and isodisomy regions, the absence of paternal allele and
      presence of two maternal alleles, with only one maternal allele on the region of
      DGUOK locus in 2p13.1. This is the first demonstration of matUPD2 with segmental
      isodisomy at 2p13.1 locus in hepatocerebral mitochondrial DNA depletion syndrome.
      The identification of UPD2 will impact genetic counseling for the proband's
      parents. Because the recurrence risk for UPD2 is very low, the risk for disease
      in further offspring for this couple is negligible.

PMID- 23141464
TI  - Peroxisome deficient aP2-Pex5 knockout mice display impaired white adipocyte and
      muscle function concomitant with reduced adrenergic tone.
AB  - Peroxisomes are essential for intermediary lipid metabolism, but the role of
      these organelles has been primarily studied in the liver. We recently generated
      aP2-Pex5 conditional knockout mice that due to the nonselectivity of the aP2
      promoter, not only had dysfunctional peroxisomes in the adipose tissue but also
      in the central and peripheral nervous system, besides some other tissues.
      Peroxisomes were however intact in the liver, heart, pancreas and muscle.
      Surprisingly, these mice not only showed dysfunctional white adipose tissue with
      increased fat mass and reduced lipolysis but also the skeletal muscle was
      affected including impaired shivering thermogenesis, reduced motor performance
      and increased insulin resistance. Non-shivering thermogenesis by brown adipose
      tissue was not altered. Strongly reduced levels of plasma adrenaline and to a
      lesser extent noradrenaline, impaired expression of catecholamine synthesizing
      enzymes in the adrenal medulla and reversal of all pathologies after
      administration of the beta-agonist isoproterenol indicated that beta-adrenergic
      signaling was reduced. Based on normal white adipose and muscle function in
      Nestin-Pex5 and Wnt-Pex5 knockout mice respectively, it is unlikely that
      peroxisome absence from the central and peripheral nervous system caused the
      phenotype. We conclude that peroxisomal metabolism is necessary to maintain the
      adrenergic tone in mice, which in turn determines metabolic homeostasis.

PMID- 23141466
TI  - Centenary celebration of Joseph Lister's death.

PMID- 23141465
TI  - Evidence for involvement of medium chain acyl-CoA dehydrogenase in the metabolism
      of phenylbutyrate.
AB  - Sodium phenylbutyrate is used for treating urea cycle disorders, providing an
      alternative for ammonia excretion. Following conversion to its CoA ester,
      phenylbutyryl-CoA is postulated to undergo one round of beta-oxidation to
      phenylacetyl-CoA, the active metabolite. Molecular modeling suggests that medium
      chain acyl-CoA dehydrogenase (MCAD; EC 1.3.99.3), a key enzyme in straight chain
      fatty acid beta-oxidation, could utilize phenylbutyryl-CoA as substrate.
      Moreover, phenylpropionyl-CoA has been shown to be a substrate for MCAD and its
      intermediates accumulate in patients with MCAD deficiency. We have examined the
      involvement of MCAD and other acyl-CoA dehydrogenases (ACADs) in the metabolism
      of phenylbutyryl-CoA. Anaerobic titration of purified recombinant human MCAD with
      phenylbutyryl-CoA caused changes in the MCAD spectrum that are similar to those
      induced by octanoyl-CoA, its bona fide substrate, and unique to the development
      of the charge transfer ternary complex. The calculated apparent dissociation
      constant (K(D app)) for these substrates was 2.16 MUM and 0.12 MUM, respectively.
      The MCAD reductive and oxidative half reactions were monitored using the electron
      transfer flavoprotein (ETF) fluorescence reduction assay. The catalytic
      efficiency and the K(m) for phenylbutyryl-CoA were 0.2 mM 34(-1).sec(-1) and 5.3
      MUM compared to 4.0 mM(-1).sec(-1) and 2.8 MUM for octanoyl-CoA. Extracts of wild
      type and MCAD-deficient lymphoblast cells were tested for the ability to reduce
      ETF using phenylbutyryl-CoA as substrate. While ETF reduction activity was
      detected in extracts of wild type cells, it was undetectable in extracts of cells
      deficient in MCAD. The results are consistent with MCAD playing a key role in
      phenylbutyrate metabolism.

PMID- 23141467
TI  - Expert practical operative skills teaching in Trauma and Orthopaedics at a
      nominal cost.
AB  - BACKGROUND AND PURPOSE: The AO Foundation Operative Fracture Management course is
      the gold standard in training courses currently available for trainees at ST3
      level. We have devised a low cost operative skills course comprising
      instructional lectures, demonstrations and practical dry bone workshops. To
      assess the quality of teaching, candidates' feedback was analysed in two cohorts
      for the running of the course over two consecutive years: 2008 and 2009. METHODS:
      Trainees were given short instructional lectures by consultant surgeons followed
      by workshops, with a trainer to candidate ratio of 1:4. A trauma inventory was
      provided by Stryker Trauma UK, ensuring a nominal fee for each candidate (L50).
      Feedback was anonymously collected according to a Likert scale and analysed using
      non-parametric methods appropriate for ranked data. MAIN FINDINGS: Twenty one of
      22 (95%) candidates gave feedback in 2008 and 18 out of 18 candidates (100%) in
      2009. The teaching provided was highly rated consistently for both years, apart
      from an informal session on theatre tips and tricks in 2008. This was not
      repeated in 2009 to allow more practical time. Only one session, an
      intramedullary nailing lecture, had a significant difference in scores between
      the 2 years (p = 0.044) because of improved scores in 2009. CONCLUSIONS: Due to
      changes in training, trainees have reduced exposure in theatre and this has
      implications for the early stages of acquiring practical operative skills. As an
      adjunct to the AO course, practical skills teaching by consultants in the format
      of a low cost skills workshop outside of a theatre environment can be achieved
      with support from a trauma implant supplier.

PMID- 23141468
TI  - A review of major trauma admissions to a tertiary adult referral hospital over a
      ten year period: fewer patients, similar survival.
AB  - BACKGROUND: Trauma is an important cause for presentation to the emergency
      department, representing a significant number of emergency surgical admissions.
      Societal changes result in alterations in the epidemiology of trauma. OBJECTIVES:
      This study aimed to review patients admitted to a tertiary referral hospital as a
      result of traumatic injuries, assessing for changes in admission epidemiology.
      METHODS: Trauma admissions over two year-long periods a decade apart were
      reviewed. The Trauma Audit and Research Network (TARN) audit system identified
      admissions and transfers between June 2006 and May 2007. The Hospital In-Patient
      Enquiry (HIPE) system identified those fulfilling TARN criteria a decade earlier.
      Comparative analysis was performed on the dataset. RESULTS: There were 367 trauma
      admissions between June 2006 and May 2007: 88 road traffic accidents (RTAs), 201
      falls and 77 other injuries, with 627 admissions a decade earlier: 286 RTAs, 247
      falls and 94 others. Males comprised 72% and 69% of RTA admissions in both
      periods respectively. Firearm-related injuries increased significantly (p =
      0.015). Neurosurgical transfers decreased from 256 to 150 with a slight increase
      in unadjusted overall mortality from 8.5% to 10.9%. Admissions of patients aged
      less than 19 reduced from 150 to 59 (p = 0.0031) with a similar trend in those
      aged between 20 and 29 years from 149 to 78. CONCLUSION: Admissions resulting
      from RTAs and of patients aged under 30 reduced significantly, however, young
      males remain the most affected sub-group. Firearm injuries increased
      significantly, a worrying trend in view of the severity of injury sustained by
      these victims.

PMID- 23141469
TI  - Use of arthroscopic "Alligator" forceps for the removal of excess cement in
      unicompartmental knee arthroplasty.

PMID- 23141470
TI  - Lipid metabolism after an oral fat test meal is affected by age-associated
      features of metabolic syndrome, but not by age.
AB  - OBJECTIVE: Postprandial lipemia influences the development of atherosclerosis.
      Age has been defined as a regulating factor of the extent of postprandial
      lipemia, but its independence of other age-associated phenotypic features, such
      as metabolic syndrome, has not been fully elucidated. METHODS: To investigate if
      age is an independent factor influencing postprandial lipemia, we compared the
      lipemic response to a rich fatty meal (60% fat) of 88 healthy young men (<30
      years old) and 97 older participants (77 metabolic syndrome patients aged > 40;
      and 20 healthy people > 65) (all ApoE3/E3), at fasting state and at 2nd and 4th
      postprandial hours. RESULTS: We didn't find differences between the healthy young
      men and the healthy elderly. The metabolic syndrome patients displayed a higher
      postprandial TG area below the curve than the other two cohorts p < 0.001. ANOVA
      for repeated measurements confirmed that these differences were significant at
      every time-point (fasting, 2 h and 4 h). Concomitant higher responses for Large
      and Small TRL-carried TG and Chol were found in these metabolic syndrome
      patients. Interestingly, the most significant differences were found for Small
      TRL-carried particles, which suggest that this fact may be mainly due to impaired
      lipid clearance. CONCLUSION: Metabolic syndrome may account for the differences
      in postprandial lipemia that have been attributed to age. In our study, there
      were no significant differences in postprandial lipemia between a young
      population (mean age 22.6 years) and a healthy people >65 years one (67.2 years)
      without metabolic syndrome.

PMID- 23141471
TI  - Effects of menopause and hormone replacement therapy on the associations of
      hyperuricemia with mortality.
AB  - OBJECTIVE: Serum uric acid (SUA) levels have been associated with cardiovascular
      and all-cause mortality. It remains unclear whether these associations differ by
      gender, menopausal status and hormone replacement therapy (HRT) and whether they
      persist after adjustment for known cardiovascular risk factors. METHODS: We
      determined the associations between fasting SUA level and death certificate-based
      mortality among 5856 participants of the third US National Health and Nutrition
      Examination Survey aged >=20 years recruited between 1988 and 1994 and followed
      for mortality until December 2006 (mean follow-up: 13.5 years; maximum follow-up:
      18 years). Cox proportional hazards regression analysis was used to adjust for
      demographic characteristics, cardiovascular risk factors and other variables
      potentially associated with SUA levels. RESULTS: Among women, SUA level was
      associated with all-cause and cardiovascular mortality (adjusted hazard ratio
      [AHR] 1.17, 95% CI 1.03-1.32 and AHR 1.23 (1.01-1.51) respectively per unit
      increase in SUA. These associations persisted among postmenopausal but not
      premenopausal women. Furthermore, among postmenopausal women, significant
      associations were identified between SUA and all-cause (AHR 1.30 [1.11-1.51]) or
      cardiovascular (AHR 1.61 [1.33-1.94]) mortality only among women not taking HRT,
      but not among women on HRT. We did not identify associations between SUA levels
      and all-cause or cardiovascular mortality in men, either under or over 51 years
      of age, in unadjusted or adjusted analyses. CONCLUSIONS: SUA level predicts
      cardiovascular and all-cause mortality independently of major predictors and risk
      factors in postmenopausal women not taking HRT but not in premenopausal women,
      postmenopausal women on HRT, or men.

PMID- 23141472
TI  - Is the higher risk of cardiovascular disease amongst South Asian populations
      linked to abnormalities of haemoglobin? A preliminary case control study.
AB  - The elevated burden of cardiovascular disease (CVD) amongst South Asian
      populations is a complex and multi-factorial phenomenon. South Asians evolved
      from environments where malaria was endemic, and while haemoglobin disorders
      frequent this group, a link to CVD has not been described. Using a case-control
      feasibility study, haemoglobin abnormalities identified by mass spectrometry were
      compared between South Asian patients with CVD (n = 72) and non-CVD controls (n =
      84). Carotid-artery intima media thickness (CIMT) was used as a marker of
      vascular damage. Ultracentrifugation was used to separate lipoprotein
      subfractions, which were analysed for iron. Haemoglobin anomalies were more
      frequent for CVD patients than controls (34.7% vs. 14.3%, P < 0.001), as were
      subfractionated lipoprotein concentrations of iron (P < 0.001). Patients with
      haemoglobin disorders had greater CIMT (0.75 vs. 0.65 mm, P = 0.008), and lower
      HDL cholesterol (0.78 vs. 1.03 mmol/l, P = 0.003). These preliminary data suggest
      that haemoglobin disorders contribute to atherosclerotic disease in South Asians
      and further research is warranted.

PMID- 23141473
TI  - Engineering Escherichia coli for production of C12-C14 polyhydroxyalkanoate from
      glucose.
AB  - Demand for sustainable materials motivates the development of microorganisms
      capable of synthesizing products from renewable substrates. A challenge to
      commercial production of polyhydroxyalkanoates (PHA), microbially derived
      polyesters, is engineering metabolic pathways to produce a polymer with the
      desired monomer composition from an unrelated and renewable source. Here, we
      demonstrate a metabolic pathway for converting glucose into medium-chain-length
      (mcl)-PHA composed primarily of 3-hydroxydodecanoate monomers. This pathway
      combines fatty acid biosynthesis, an acyl-ACP thioesterase to generate desired
      C12 and C14 fatty acids, beta-oxidation for conversion of fatty acids to (R)-3
      hydroxyacyl-CoAs, and a PHA polymerase. A key finding is that Escherichia coli
      expresses multiple copies of enzymes involved in beta-oxidation under aerobic
      conditions. To produce polyhydroxydodecanoate, an acyl-ACP thioesterase (BTE), an
      enoyl-CoA hydratase (phaJ3), and mcl-PHA polymerase (phaC2) were overexpressed in
      E. coli DeltafadRABIJ. Yields were improved through expression of an acyl-CoA
      synthetase resulting in production over 15% CDW--the highest reported production
      of mcl-PHA of a defined composition from an unrelated carbon source.

PMID- 23141474
TI  - Membrane-initiated estradiol signaling regulates the central nervous system.

PMID- 23141475
TI  - Treatment of atypical hemolytic uremic syndrome and thrombotic microangiopathies:
      a focus on eculizumab.
AB  - Uncontrolled complement activation is central to the occurrence of atypical
      hemolytic uremic syndrome (aHUS) and can result in thrombotic microangiopathies
      (TMAs). These terms encompass a group of heterogenic inherited or acquired
      diseases that recent research suggests may be triggered by the complement
      cascade. Pathogenetic triggers of complement activation include immunologic
      disorders, genetics, infections, systemic diseases, pregnancy, drug
      administration, metabolic diseases, transplantation, or triggers of mixed cause.
      Hallmarks of aHUS and other TMAs include increased vascular endothelium
      thromboresistance, leukocyte adhesion to damaged endothelium, complement
      consumption, coagulation abnormalities, and vascular shear stress, whereas common
      end points of these mechanisms include hemolytic anemia, thrombocytopenia with
      microvascular infarction, and predisposition for decreased kidney function and
      other organ involvement. The central role of the complement cascade as a disease
      trigger suggests a possible therapeutic target. Eculizumab, a first-in-class
      humanized monoclonal anti-C5 antibody that has been successful in the treatment
      of paroxysmal nocturnal hemoglobinuria, a disorder of complement-induced
      hemolytic anemia, received approval for the treatment of aHUS in the United
      States and Europe in late 2011. We review the treatment of aHUS and other TMAs,
      focusing on the role of eculizumab, including its pharmacology, mechanism of
      action, and approved dosing recommendations and health economic considerations.
      Finally, the potential for future indications for eculizumab use in other
      complement-driven diseases is discussed.

PMID- 23141476
TI  - Direct photochemistry of three fluoroquinolone antibacterials: norfloxacin,
      ofloxacin, and enrofloxacin.
AB  - Fluoroquinolone (FQ) antibacterial compounds are frequently detected in the
      aquatic environment, and photodegradation is expected to play an important role
      in FQ fate in some sunlit surface waters. This study investigated the direct
      aquatic photochemistry of three FQs: norfloxacin, ofloxacin, and enrofloxacin.
      The direct photolysis rate of each drug exhibited strong pH dependence when
      exposed to simulated sunlight. For each FQ, direct photolysis rates and total
      light absorbance were used to calculate quantum yields for each of three
      environmentally relevant protonation states: a cationic, a zwitterionic, and an
      anionic form. In each case, quantum yields of the species varied significantly.
      The quantum yield for the zwitterionic form was 2-3 times higher than that of the
      anionic form and over an order of magnitude higher than that of the cationic
      form. Antibacterial activity assays were used to determine whether the loss of
      parent FQ due to photolysis led to loss of activity. Norfloxacin and ofloxacin
      photoproducts were found to be inactive, whereas enrofloxacin photoproducts were
      found to retain significant activity. These results are important for aiding in
      predictions of the potential impacts of FQs in surface waters.

PMID- 23141477
TI  - C-REDOR curves of extended spin systems.
AB  - The convergence of simulated C-REDOR curves of (infinitely) large spin systems is
      investigated with respect to the number of spins considered in the calculations.
      Taking a sufficiently large number of spins (>20,000 spins) into account enables
      the simulation of converged C-REDOR curves over the entire time period and not
      only the initial regime. The calculations are based on an existing approximation
      within first order average Hamiltonian theory (AHT), which assumes the absence of
      homonuclear dipole-dipole interactions. The C-REDOR experiment generates an
      average Hamiltonian close to the idealized AHT behavior even for multiple spin
      systems including multiple homonuclear dipole-dipole interactions which is shown
      from numerically exact calculations of the spin dynamics. Experimentally it is
      shown that calculations accurately predict the full, experimental C-REDOR curves
      of the multi-spin systems (31)P-(19)F in apatite, (31)P-(1)H in potassium
      trimetaphosphimate and (1)H-(31)P in potassium dihydrogen phosphate. We also
      present (13)C-(1)H and (15)N-(1)H data for the organic compounds glycine, l
      alanine and l-histidine hydrochloride monohydrate which require consideration of
      molecular motion. Furthermore, we investigated the current limits of the method
      from systematic errors and we suggest a simple way to calculate errors for
      homogeneous and heterogeneous samples from experimental data.

PMID- 23141479
TI  - A novel endovascular technique in the management of a large internal iliac artery
      aneurysm associated with an arteriovenous fistula.
AB  - PURPOSE: To describe a novel endovascular technique in the management of a
      complex arteriovenous fistula between a large internal iliac artery aneurysm and
      the adjacent iliac vein in a 76-year old patient with previous aortobifemoral
      bypass graft with an occluded proximal common iliac artery. CASE REPORT: Due to
      the high risk of open surgery in this case, endovascular treatment with
      simultaneous venous and arterial access was performed, with implantation of 2
      stent grafts in the iliac vein to cover the fistulous communication and
      embolisation of the native external iliac artery (inflow). CONCLUSION: The
      endovascular technique described enables thrombosis of the large internal iliac
      aneurysm and treatment of the arteriovenous fistula without exposing the patient
      to the high morbidity and mortality associated with open surgery.

PMID- 23141478
TI  - Metabolite concentrations in the anterior cingulate cortex predict high
      neuropathic pain impact after spinal cord injury.
AB  - Persistent pain is a common reason for reduced quality of life after a spinal
      cord injury (SCI). Biomarkers of neuropathic pain may facilitate translational
      research and the understanding of underlying mechanisms. Research suggests that
      pain and affective distress are anatomically and functionally integrated in the
      anterior cingulate cortex and can modulate sensory and affective aspects of pain.
      We hypothesized that severe neuropathic pain with a significant psychosocial
      impact would be associated with metabolite concentrations (obtained by magnetic
      resonance spectroscopy) in the anterior cingulate cortex, indicating neuronal
      and/or glial dysfunction. Participants with SCI and severe, high-impact
      neuropathic pain (SCI-HPI; n=16), SCI and moderate, low-impact neuropathic pain
      (SCI-LPI; n=24), SCI without neuropathic pain (SCI-noNP; n=14), and able-bodied,
      pain-free control subjects (A-B; n=22) underwent a 3-T magnetic resonance imaging
      brain scan. Analyses revealed that the SCI-HPI group had significantly higher
      levels of myoinositol (Ins) (P<.000), creatine (P=.007), and choline (P=.014),
      and significantly lower levels of N-acetyl aspartate/Ins (P=.024) and glutamate
      glutamine (Glx)/Ins (P=.003) ratios than the SCI-LPI group. The lower Glx/Ins
      ratio significantly discriminated between SCI-HPI and the A-B (P=.006) and SCI
      noNP (P=.026) groups, displayed excellent test-retest reliability, and was
      significantly related to greater pain severity, interference, and affective
      distress. This suggests that the combination of lower glutamatergic metabolism
      and proliferation of glia and glial activation are underlying mechanisms
      contributing to the maintenance of severe neuropathic pain with significant
      psychosocial impact in chronic SCI. These findings indicate that the Glx/Ins
      ratio may be a useful biomarker for severe SCI-related neuropathic pain with
      significant psychosocial impact.

PMID- 23141480
TI  - The VMO:VL activation ratio while squatting with hip adduction is influenced by
      the choice of recording electrode.
AB  - Concomitant hip adduction during squatting has long been advocated as a
      rehabilitative method to preferentially activate the VMO in persons with
      patellofemoral pain. This practice however has been based on research using
      surface electrodes which are prone to crosstalk from neighboring muscles (i.e.,
      adductor magnus). This study sought to determine whether activation levels of the
      VMO relative to the VL while squatting with hip adduction would differ based on
      the choice of recording electrode. Ten healthy subjects performed a maneuver with
      hip adduction and without hip adduction. The mean VMO and VL activation levels
      were recorded simultaneously with surface and indwelling fine-wire electrodes.
      For both recording electrodes, the VMO and VL activity increased significantly
      with the addition of hip adduction (p < 0.05). However, the increase in VMO
      activation was more pronounced with surface electrodes, resulting in a
      significantly higher VMO:VL ratio with the incorporation of hip adduction
      compared to without hip adduction (p < 0.05). No difference in the VMO:VL ratio
      was observed between the two squat conditions for the fine-wire electrodes (p >
      0.05). Our findings suggest that the VMO:VL activation ratio when squatting with
      hip adduction is influenced by electrode choice.

PMID- 23141481
TI  - Adaptive rehabilitation games.
AB  - In conventional neuromuscular rehabilitation, patients are required to perform
      biomechanical exercises to recover their neuromotor abilities. These
      physiotherapeutic tasks are defined by the physiotherapist, according to his
      estimate of the patient's pathologic neuromotor function. The definition of the
      task is mainly qualitative and it is often merely demonstrated to the patient as
      a gesture to reproduce. Success of the treatment relies then on the accuracy and
      repetition of the motor training. We propose a novel approach to neuromotor
      training by combining the advantages of a virtual reality platform with
      biofeedback information on the training subject from biometric equipment and with
      the computational power of artificial neural networks. In a calibration stage,
      the subject performs motor training on a known task to train the network. Once
      trained, the tuned network generates a new patient-specific task, based on the
      definition of the subject's expected performance dictated by the therapist. The
      system was tested for upper limb rehabilitation on healthy subjects. We measured
      a 33% improvement in the triceps performance (p = 0.027). The novelty of the
      proposed approach lies in its use of learning systems to the estimation of
      biological models.

PMID- 23141482
TI  - Renal artery stenosis after renal sympathetic denervation.

PMID- 23141483
TI  - A novel low-energy electrotherapy that terminates ventricular tachycardia with
      lower energy than a biphasic shock when antitachycardia pacing fails.
AB  - OBJECTIVES: The authors sought to develop a low-energy electrotherapy that
      terminates ventricular tachycardia (VT) when antitachycardia pacing (ATP) fails.
      BACKGROUND: High-energy implantable cardioverter-defibrillator (ICD) shocks are
      associated with device failure, significant morbidity, and increased mortality. A
      low-energy alternative to ICD shocks is desirable. METHODS: Myocardial infarction
      was created in 25 dogs. Sustained, monomorphic VT was induced by programmed
      stimulation. Defibrillation electrodes were placed in the right ventricular apex,
      and coronary sinus and left ventricular epicardium. If ATP failed to terminate
      sustained VT, the defibrillation thresholds (DFTs) of standard versus
      experimental electrotherapies were measured. RESULTS: Sustained VT ranged from
      276 to 438 beats/min (mean 339 beats/min). The right ventricular-coronary sinus
      shock vector had lower impedance than the right ventricular-left ventricular
      patch (54.4 +/- 18.1 Omega versus 109.8 +/- 16.9 Omega; p < 0.001). A single
      shock required between 0.3 +/- 0.2 J to 5.9 +/- 2.5 J (mean 2.64 +/- 3.22 J; p =
      0.008) to terminate VT, and varied depending upon the phase of the VT cycle in
      which it was delivered. By contrast, multiple shocks delivered within 1 VT cycle
      length were not phase dependent and achieved lower DFT compared with a single
      shock (0.13 +/- 0.09 J for 3 shocks, 0.08 +/- 0.04 J for 5 shocks, and 0.09 +/-
      0.07 J for 7 shocks; p < 0.001). Finally, a multistage electrotherapy (MSE)
      achieved significantly lower DFT compared with a single biphasic shock (0.03 +/-
      0.05 J versus 2.37 +/- 1.20 J; respectively, p < 0.001). At a peak shock
      amplitude of 20 V, MSE achieved 91.3% of terminations versus 10.5% for a biphasic
      shock (p < 0.001). CONCLUSIONS: MSE achieved a major reduction in DFT compared
      with a single biphasic shock for ATP-refractory monomorphic VT, and represents a
      novel electrotherapy to reduce high-energy ICD shocks.

PMID- 23141484
TI  - Dysfunctional high-density lipoprotein in patients on chronic hemodialysis.
AB  - OBJECTIVES: This study examined the functionality of high-density lipoprotein
      (HDL) in individuals with end-stage renal disease on dialysis (ESRD-HD).
      BACKGROUND: The high rate of cardiovascular disease (CVD) in chronic kidney
      disease is not explained by standard risk factors, especially in patients with
      ESRD-HD who appear resistant to benefits of statin therapy. HDL is
      antiatherogenic because it extracts tissue cholesterol and reduces inflammation.
      METHODS: Cellular cholesterol efflux and inflammatory response were assessed in
      macrophages exposed to HDL of patients with ESRD-HD or controls. RESULTS: HDL
      from patients with ESRD-HD was dramatically less effective than normal HDL in
      accepting cholesterol from macrophages (median 6.9%; interquartile range [IQR]:
      1.4% to 10.2%) versus control (median 14.9%; IQR: 9.8% to 17.8%; p < 0.001). The
      profound efflux impairment was also seen in patients with ESRD-HD and diabetes
      compared with patients with diabetes without renal disease (median 8.1%; IQR:
      3.3% to 12.9%) versus control (median 13.6%; IQR: 11.0% to 15.9%; p = 0.009). In
      vitro activation of cellular cholesterol transporters increased cholesterol
      efflux to both normal and uremic HDL. HDL of patients with ESRD-HD had reduced
      antichemotactic ability and increased macrophage cytokine response (tumor
      necrosis factor-alpha, interleukin-6, and interleukin-1-beta). HDL of patients
      with ESRD-HD on statin therapy had reduced inflammatory response while
      maintaining impaired cholesterol acceptor function. Interestingly, impaired HDL
      mediated efflux did not correlate with circulating C-reactive protein levels or
      cellular inflammatory response. CONCLUSIONS: These findings suggest that abnormal
      HDL capacity to mediate cholesterol efflux is a key driver of excess CVD in
      patients on chronic hemodialysis and may explain why statins have limited effect
      to decrease CV events. The findings also suggest cellular cholesterol
      transporters as potential therapeutic targets to decrease CV risk in this
      population.

PMID- 23141485
TI  - Relations of long-term and contemporary lipid levels and lipid genetic risk
      scores with coronary artery calcium in the framingham heart study.
AB  - OBJECTIVES: This study evaluated the association of timing of lipid levels and
      lipid genetic risk score (GRS) with subclinical atherosclerosis. BACKGROUND:
      Atherosclerosis is a slowly progressive disorder influenced by suboptimal lipid
      levels. Long-term versus contemporary lipid levels may more strongly impact the
      development of coronary artery calcium (CAC). METHODS: Framingham Heart Study
      (FHS) Offspring Cohort participants (n = 1,156, 44% male, 63 +/- 9 years)
      underwent serial fasting lipids (low-density lipoprotein cholesterol [LDL-C],
      high-density lipoprotein, and triglycerides), Exam 1 (1971 to 1975) to Exam 7
      (1998 to 2001). FHS Third Generation Cohort participants (n = 1,954, 55% male, 45
      +/- 6 years) had fasting lipid profiles assessed, 2002 to 2005. Computed
      tomography (2002 to 2005) measured CAC. Lipid GRSs were computed from
      significantly associated single-nucleotide polymorphisms. The association between
      early, long-term average, and contemporary lipids, and lipid GRS with elevated
      CAC was assessed using logistic regression. RESULTS: In FHS Offspring, Exam 1 and
      long-term average as compared with Exam 7 lipid measurements, including untreated
      lipid levels, were strongly associated with elevated CAC. In the FHS Third
      Generation, contemporary lipids were associated with CAC. The LDL-C GRS was
      associated with CAC (age-/sex-adjusted odds ratio: 1.14, 95% confidence interval:
      1.00 to 1.29, p = 0.04). However, addition of the GRS to the lipid models did not
      result in a significant increase in the odds ratio or C-statistic for any lipid
      measure. CONCLUSIONS: Early and long-term average lipid levels, as compared with
      contemporary measures, are more strongly associated with elevated CAC. Lipid GRS
      was associated with lipid levels but did not predict elevated CAC. Adult early
      and long-term average lipid levels provide important information when assessing
      subclinical atherosclerosis and cardiovascular risk.

PMID- 23141487
TI  - Atrial fibrillation and diffuse left ventricular fibrosis, a causal association?

PMID- 23141486
TI  - Dietary sodium restriction reverses vascular endothelial dysfunction in middle
      aged/older adults with moderately elevated systolic blood pressure.
AB  - OBJECTIVES: This study sought to determine the efficacy of dietary sodium
      restriction (DSR) for improving vascular endothelial dysfunction in middle
      aged/older adults with moderately elevated systolic blood pressure (SBP) (130-159
      mm Hg) and the associated physiological mechanisms. BACKGROUND: Vascular
      endothelial dysfunction develops with advancing age and elevated SBP,
      contributing to increased cardiovascular risk. DSR lowers BP, but its effect on
      vascular endothelial function and mechanisms involved are unknown. METHODS:
      Seventeen subjects (11 men and 6 women; mean age, 62 +/- 7 years) completed a,
      randomized crossover study of 4 weeks of both low (DSR) and normal sodium intake.
      Vascular endothelial function (endothelium-dependent dilation; EDD), nitric oxide
      (NO)/tetrahydrobiopterin (BH(4)) bioavailability, and oxidative stress-associated
      mechanisms were assessed following each condition. RESULTS: Urinary sodium
      excretion was reduced by ~ 50% (to 70 +/- 30 mmol/day), and conduit (brachial
      artery flow-mediated dilation [FMD(BA)]) and resistance (forearm blood flow
      responses to acetylcholine [FBF(ACh)]) artery EDD were 68% and 42% (peak
      FBF(ACh)) higher following DSR (p < 0.005). Low sodium markedly enhanced NO
      mediated EDD (greater DeltaFBF(ACh) with endothelial NO synthase inhibition)
      without changing endothelial NO synthase expression/activation (Ser 1177
      phosphorylation), restored BH(4) bioactivity (less DeltaFMD(BA) with acute
      BH(4)), abolished tonic superoxide suppression of EDD (less DeltaFMD(BA) and
      DeltaFBF(ACh) with ascorbic acid infusion), and increased circulating superoxide
      dismutase activity (all p < 0.05). These effects were independent of DeltaSBP.
      Other subject characteristics/dietary factors and endothelium-independent
      dilation were unchanged. CONCLUSIONS: DSR largely reversed both macro- and
      microvascular endothelial dysfunction by enhancing NO and BH(4) bioavailability
      and reducing oxidative stress. Our findings support the emerging concept that DSR
      induces "vascular protection" beyond that attributable to its BP-lowering
      effects.

PMID- 23141488
TI  - Excessive sodium intake and cardiovascular disease: a-salting our vessels.

PMID- 23141489
TI  - Evolution of the implantable cardioverter-defibrillator: from bullets to BBs.

PMID- 23141490
TI  - Referral patterns and perceived barriers to adult congenital heart disease care:
      results of a survey of U.S. pediatric cardiologists.
AB  - OBJECTIVES: This study sought to elucidate referral patterns and barriers to
      adult congenital heart disease (ACHD) care, as perceived by pediatric
      cardiologists (PCs). BACKGROUND: Management guidelines recommend that care of
      adults with moderate/complex congenital heart disease be guided by clinicians
      trained in ACHD. METHODS: A cross-sectional survey was distributed to randomly
      selected U.S. PCs. RESULTS: Overall response rate was 48% (291 of 610); 88% (257
      of 291) of respondents met inclusion criteria (outpatient care to patients >11
      years of age). Participants were in practice for 18.2 +/- 10.7 years; 70% were
      male, and 72% were affiliated with an academic institution; 79% stated that they
      provide care to adults (>18 years). The most commonly perceived patient
      characteristic prompting referral to ACHD care was adult comorbidities (83%). The
      most perceived barrier to ACHD care was emotional attachment of parents and
      patients to the PC (87% and 86%, respectively). Clinician attachment to the
      patient/family was indicated as a barrier by 70% of PCs and was more commonly
      identified by responders with an academic institutional affiliation (p = 0.001).
      A lack of qualified ACHD care providers was noted by 76% of PCs. Those affiliated
      with an academic institution were less likely to identify this barrier to ACHD
      care (p = 0.002). CONCLUSIONS: Most PC respondents in the United States provide
      care to ACHD patients. Common triggers that prompt referral and perceived
      barriers to ACHD care were identified. These findings might assist ACHD programs
      in developing strategies to identify and retain patients, improve collaborative
      care, and address emotional needs during the transition and transfer process.

PMID- 23141491
TI  - Eligibility for renal denervation in patients with resistant hypertension: when
      enthusiasm meets reality in real-life patients.

PMID- 23141492
TI  - High-density lipoproteins: from function to therapy.

PMID- 23141493
TI  - Diffuse ventricular fibrosis in atrial fibrillation: noninvasive evaluation and
      relationships with aging and systolic dysfunction.
AB  - OBJECTIVES: The purpose of this study was to evaluate diffuse myocardial fibrosis
      of the left ventricle (LV) in patients with atrial fibrillation (AF). BACKGROUND:
      Diffuse myocardial fibrosis is a hallmark of cardiomyopathy. Unlike replacement
      fibrosis, it is not visualized on delayed-enhancement cardiac magnetic resonance
      (CMR) imaging, but may be quantified with contrast-enhanced T(1) mapping methods.
      In atrial fibrillation (AF), it may be induced by arrhythmia or reflect pre
      existing cardiomyopathy. METHODS: Ninety subjects underwent CMR using a clinical
      1.5-T scanner: 23 controls, 40 paroxysmal AF patients, and 27 persistent AF
      patients. Cardiac morphology and function was evaluated from CMR cine imaging. A
      histologically validated T(1) mapping sequence was used to calculate post
      contrast T(1) relaxation time (T(1) time) of the LV myocardium as an index of
      diffuse myocardial fibrosis. RESULTS: Age was similar across controls, paroxysmal
      AF patients, and persistent AF patients (54 +/- 12 years, 58 +/- 9 years, and 56
      +/- 10 years, p = NS). Persistent AF patients had larger indexed left atrium
      volume (55 +/- 18 ml vs. 41 +/- 12 ml and 47 +/- 14 ml) and lower ejection
      fraction (54 +/- 10% vs. 65 +/- 6% and 61 +/- 8%) than controls and paroxysmal AF
      patients (p < 0.05). Post-contrast ventricular T(1) time differed across all
      groups (controls, 535 +/- 86 ms; paroxysmal AF, 427 +/- 95 ms; persistent AF, 360
      +/- 84 ms; p < 0.001). Univariate predictors of post-contrast ventricular T(1)
      time included age, sex, AF category, ejection fraction, LV mass, congestive heart
      failure, and body mass index. After multivariate analysis, age, AF category, and
      ejection fraction remained independent predictors. CONCLUSIONS: Post-contrast
      ventricular T(1) mapping identifies diffuse LV fibrosis in patients with AF and
      provides new insights into the association between AF and adverse ventricular
      remodeling.

PMID- 23141494
TI  - What have we learned about patients with heart failure and preserved ejection
      fraction from DIG-PEF, CHARM-preserved, and I-PRESERVE?
AB  - Examination of patients with reduced and preserved ejection fraction in the DIG
      (Digitalis Investigation Group) trials and the CHARM (Candesartan in Heart
      Failure: Assessment of Reduction in Mortality and Morbidity) trials provides
      comparisons of outcomes in each of these types of heart failure. Comparison of
      the patients in these trials, along with the I-PRESERVE (Irbesartan in Heart
      Failure with Preserved Systolic Function Trial), with patients of similar age,
      sex distribution, and comorbidity in trials of hypertension, diabetes mellitus,
      angina pectoris, and atrial fibrillation provides even more interesting insights
      into the relation between phenotype and rates of death and heart failure
      hospitalization. The poor clinical outcomes in patients with heart failure and
      preserved ejection fraction do not seem easily explained on the basis of age,
      sex, comorbidity, blood pressure, or left ventricular structural remodeling but
      do seem to be explained by the presence of the syndrome of heart failure.

PMID- 23141495
TI  - Discontinuation of long-term clopidogrel therapy is associated with death and
      myocardial infarction after saphenous vein graft percutaneous coronary
      intervention.
AB  - OBJECTIVES: This study sought to examine the pattern of death and myocardial
      infarction (MI) after clopidogrel cessation in patients undergoing percutaneous
      coronary intervention (PCI) of the saphenous vein graft (SVG). BACKGROUND: The
      timing and incidence of adverse events by different durations of clopidogrel
      therapy after SVG PCI remain unknown. METHODS: This is a cohort study of patients
      undergoing SVG PCI between 2000 and 2009, followed for all-cause mortality or MI
      after stopping clopidogrel. Incidence rates were calculated across different time
      periods after clopidogrel cessation. Adjusted incidence rate ratios (IRR) were
      calculated with multivariable regression (piecewise exponential and Poisson).
      RESULTS: There were 603 patients who underwent SVG PCI, of which 411 were event
      free at the time of clopidogrel cessation. The incidence rate (95% confidence
      interval: [CI])/1,000 person-days of death or MI after stopping clopidogrel in
      the time intervals of 0 to 90 days, 91 to 365 days, and 1 to 2 years were 1.26
      (95% CI: 0.93 to 1.70), 0.41 (95% CI: 0.30 to 0.56), and 0.41 (95% CI: 0.30 to
      0.55), respectively. In multivariable analyses, the overall IRR (95% CI) for
      death or MI in the 0- to 90-day interval after stopping clopidogrel compared with
      the 91- to 365-day interval was 2.58 (95% CI: 1.64 to 4.07). Similar results were
      observed over a broad range of clopidogrel treatment durations (<6 months, 6
      months to 1 year, 1 to 2 years, or >2 years). The results were also consistent
      across subgroups, including sex, stent type, stent diameter, PCI period, and
      diabetes status. When death alone was evaluated, there remained a significant
      increase in the event rate in the 0- to 90-day interval compared with the 91- to
      365-day interval (IRR: 2.33; 95% CI: 1.32 to 4.11). CONCLUSIONS: A clustering of
      events was observed in the initial 0 to 90 days after clopidogrel cessation in
      all treatment durations of clopidogrel investigated after SVG PCI. These results
      might have important implications in high-risk cohorts undergoing PCI. Additional
      studies are needed to elucidate the mechanisms underlying the early clustering of
      events after clopidogrel cessation.

PMID- 23141496
TI  - The circulating level of FABP3 is an indirect biomarker of microRNA-1.
AB  - OBJECTIVES: This study sought to identify proteins from the cardiomyocyte (CM)
      secretome that are directly targeted by the muscle-specific microRNA-1 (miR-1),
      and thus reflect the pathophysiological state of the CM. BACKGROUND: MicroRNAs
      play critical regulatory roles during myocardial remodeling and progression to
      heart failure. However, it remains unknown whether secreted microRNA-targeted
      proteins can be used as indicators of myocardial microRNA expression and
      function. METHODS: A proteomic analysis based on multidimensional protein
      identification technology was performed on supernatants from cultured CMs
      overexpressing miR-1. Biochemical assays and an inducible cardiac-specific
      transgenic mouse model overexpressing miR-1 were used to demonstrate that heart
      type fatty acid-binding protein-3 (FABP3) is a target of miR-1. Levels of miR-1
      and FABP3 in cardiac tissue and plasma samples from mouse models as well as human
      patients were quantified by quantitative reverse-transcription polymerase chain
      reaction and enzyme-linked immunosorbent assay, respectively. The study included
      wild-type mice subjected to ventricular pressure overload or fasting, as well as
      patients diagnosed with ventricular hypertrophy due to valvular aortic stenosis,
      acromegaly, or growth hormone deficiency, conditions associated with altered miR
      1 expression. RESULTS: An inverse relationship between myocardial expression of
      miR-1 and circulating levels of FABP3 was found both in vitro and in vivo under
      various pathological conditions. CONCLUSIONS: Assessment of FABP3 plasma levels
      in human patients might be used for indirectly measuring cardiac miR-1 activity.

PMID- 23141497
TI  - Transcatheter retrograde closure of perimembranous ventricular septal defects in
      children with the Amplatzer duct occluder II device.

PMID- 23141498
TI  - Statins in preparation for chemotherapy: "do these medications help your fitness
      for battle?".

PMID- 23141499
TI  - Effect of statin therapy on the risk for incident heart failure in patients with
      breast cancer receiving anthracycline chemotherapy: an observational clinical
      cohort study.
AB  - OBJECTIVES: The aim of this study was to evaluate the effect of continuous statin
      treatment on new-onset heart failure (HF) in patients with breast cancer
      receiving anthracycline-based chemotherapy. BACKGROUND: In vitro and animal model
      experimental studies have reported that statins prevent doxorubicin-induced
      cardiotoxicity. METHODS: A total of 628 women with newly diagnosed breast cancer
      (mean age 51.5 +/- 10.8 years) treated with anthracycline were retrospectively
      identified and studied. The primary outcome (incident HF hospitalization) was
      compared in propensity-matched patients receiving uninterrupted statin therapy
      through the follow-up period of 2.55 +/- 1.68 years and their counterparts not
      receiving continuous statin therapy. RESULTS: After propensity matching (2:1),
      the 67 patients (10.7%) receiving uninterrupted statin therapy were combined with
      134 controls. New-onset HF was observed in 67 of the 201 matched patients.
      Multivariate-matched Cox regression analysis showed a significantly lower hazard
      ratio [HR] of 0.3 (95% confidence interval [CI]: 0.1 to 0.9; p = 0.03) for
      patients taking uninterrupted statin therapy. Cardiotoxicity risk factors at the
      time of cancer diagnosis (HR: 5.0; 95% CI: 2.2 to 11.1; p < 0.001), baseline
      ejection fraction <55% (HR: 2.7; 95% CI: 1.2 to 6.3; p = 0.02), and trastuzumab
      use (HR: 3.0; 95% CI: 1.3 to 7.2; p = 0.01) were predictors of incident HF.
      CONCLUSIONS: In this analysis of female patients with breast cancer treated with
      anthracycline chemotherapy, statin use was associated with a lower risk for
      incident HF. This finding is consistent with prior animal studies and warrants
      further investigation through prospective randomized clinical trials.

PMID- 23141500
TI  - The pH of HNO donation is modulated by ring substituents in Piloty's acid
      derivatives: azanone donors at biological pH.
AB  - A group of Piloty's acid (N-hydroxybenzenesulfonamide) derivatives were
      synthesized and fully characterized in order to assess the rates and pH of HNO
      (azanone, nitroxyl) donation in aqueous media. The derivatives, with electron
      withdrawing and -donating substituents include methyl, nitro, fluoro, tri
      isopropyl, trifluoromethyl and methoxy groups. The most interesting modulation
      observed is the change in pH range in which the compounds are able to donate HNO.
      UV-visible kinetic measurements at different pH values were used to evaluate the
      decomposition rate of the donors. A novel technique based on electrochemical
      measurements using a Co-porphyrin sensor was used to assess the release of HNO as
      a function of pH, by direct measurement of [HNO]. The results were contrasted
      with DFT calculations in order to understand the electronic effects exerted by
      the ring substituents, which drastically modify the pH range of donation. For
      example, while Piloty's acid donates HNO from pH 9.3, the corresponding fluoro
      derivative starts donating at pH 4.0.

PMID- 23141501
TI  - Trace element investigations in urinary stones: a preliminary pilot case in
      Basilicata (Southern Italy).
AB  - The role of trace elements in the lithogenesis of urinary stones is still
      debated. However, it is generally appreciated that urinary stones are one of the
      most common health problems in the world and are strongly associated with
      environmental factors. It is important to highlight that urinary stones
      containing trace elements could be considered a marker of environmental
      pollution. A large set of urinary stones (48), collected among the Basilicata
      (southern Italy) inhabitants, was analysed by AAS and ICP for the content of
      specific chemical elements that were either involved in the crystallisation
      process of kidney stones (Ca, Mg, K, Zn, Fe, Cu, and Mn) or which were
      potentially toxic (Pb, Cr). Three main findings emerge from the results:
      Furthermore, the results showed that the concentrations of Zn, Cu, Fe, Pb and Cr
      were greater than that of ingested from a standard diet. Consequently, varying
      amounts of these elements may have been attributed to their enrichment in the
      diet of the inhabitants of polluted areas.

PMID- 23141503
TI  - [Reappraise the value of orbital decompression for thyroid associated
      ophthalmopathy].
AB  - Compressive optic neuropathy and exposure keratopathy is classical indications of
      orbital decompression surgery for thyroid associated ophthalmopathy. Recently,
      its therapeutic value should extend to cosmetic requirement, the entity of
      congestive orbitopathy, ocular hypertension and hormonal resistance. In order to
      improve the safe and efficacy of orbital decompressions, we need the graded
      decompression plans and the modified areas of bone removal. The preferred area of
      bone removal is deep lateral wall. In serious patients, a combined medial,
      inferior and deep lateral wall decompression is recommended. There have also been
      technical advances in the cosmetic incisions such as transconjunctival, eyelid
      crease or endoscopic access. Removing periorbital fat is a supplement skill for
      bony decompression. The removed amount and indications should be regulated
      strictly. Individual operative project is the tendency of development of orbital
      decompressions.

PMID- 23141502
TI  - From knowledge translation to engaged scholarship: promoting research relevance
      and utilization.
AB  - It is now accepted within health care that clinicians and managers should base
      their practice and decision making on evidence. One would think that this would
      be quite a simple undertaking--if good research is available and well
      communicated, people will act on it. But most of our efforts to date, which have
      focused largely on research transfer, have had modest success. This has created a
      need to reexamine the evidence--and the assumptions--on which our current
      knowledge-to-action activities are based. This article will summarize what is
      known about what works in promoting evidence-informed action, tracing the
      evolution from a linear focus on research transfer to complex strategies for user
      engagement. Using concrete examples, it will illustrate the strengths and
      limitations of various approaches and implications for rehabilitation medicine.

PMID- 23141504
TI  - [Control indications for orbital operation strictly and avoid work blindly].
AB  - There are many different orbital diseases and the orbital surgery is almost
      complex. Some severe surgical complications resulted from various factors. With
      the growing popularity of orbital treatments, most clinical units can carry out
      orbital surgery with different qualities and the number of surgery is growing day
      by day, resulting in uneven surgical effects, which may also be the cause of
      medical dispute in the near future. There are many different causes for the
      occurrence of surgical complications, for example, the complicated anatomy,
      diverse nature of the lesions, deep location and the different skills of
      operators. The correct understanding of various orbital diseases, strict control
      of surgical indications and objective assessment of the surgical quality should
      all be regarded as controllable factors, which are effective in improving
      surgical effects and avoiding surgical risks.

PMID- 23141505
TI  - [Clinical analysis of 14 cases of congenital orbital fibrosis].
AB  - OBJECTIVE: The purpose of this study was to show the clinical and imaging
      characteristics in patients with congenital orbital fibrosis. METHODS: A
      retrospective review of a series of 14 patients with congenital orbital fibrosis
      hospitalized in Institute of Orbital Disease during 2005 to 2009 have been
      characterized. Patients aged from 3 months to 18 years old, the median age was 7
      years old, 6 cases (43%) were male. RESULTS: Ocular changes were found at birth
      in all patients, symptoms at onset of the disease included dysfunction of eye
      movement (12 cases), lagophthalmos (7 cases), diplopia (5 cases), exophthalmos (4
      cases), conjunctival congestion (4 cases) and endophthalmos (2 cases). The
      results of medical examinations including visual acuity, exophthalmos or
      endophthalmos, diplopia with or without compensative head station, displacement
      of the eye, lagophthalmos, blephroptosis and ocular dyskinesia all have been
      record. In the 14 cases, 13 patients have undertaken the CT imaging examination,
      soft tissue lesions have been found in the orbit with high density and irregular
      shape, accompanied with thickened ocular muscles and anatomical changes. Of the 9
      cases which underwent MRI examination, all of the lesions showed medium signals
      in T(1)WI, with medium to low signals in T(2)WI. Local excision has been
      performed in 2 patients, we found that the orbital lesions packaged with hard
      fibrous tissues around, and the ocular muscles were thick and stark. Pathological
      examination showed fibrosis and degeneration in the lesions, lacrimal gland and
      ocular muscles. Some lymphocyte infiltration also has been observed. CONCLUSIONS:
      Congenital orbital fibrosis is an orbital disease occurs at birth and is
      characterized with series of signs such as endophthalmos or exophthalmos, ocular
      dyskinesia and diplopia. Imaging examinations often find abnormal mass with
      irregular shape and soft tissue density in orbit. Till now, no efficient therapy
      has been established.

PMID- 23141506
TI  - [Analysis of clinical features in distensible orbital venous malformations].
AB  - OBJECTIVE: To study the characteristic of the clinical and image features of
      distensible orbital venous malformations (DOVM). METHODS: It was a retrospective
      case series study. Clinical features and imaging findings, including B
      ultrasonography, CDFI, MRI, CT imaging of 43 patients with DOVM were reviewed in
      Shanghai Changzheng Hospital affiliated to Secondary Military Medical University
      RESULTS: Forty-three patients (24 women and 19 men), whose ages range from 5 to
      71 years old, showed clinical or radiological evidence of distensibility. The
      mean age was 32 years. Location of the lesion within the orbit was variable, 9
      patients with superficial lesions, and 19 patients with deep lesions. Twelve
      patients were classified as combined lesions. 3 patients with extraorbital venous
      malformations were classified as complex lesions. Twenty of 43 patients with DOVM
      were initially seen with proptosis or pain increasing with the head in a
      dependent position. Eight patients presented with a sudden onset of proptosis and
      pain secondary to thrombosis or hemorrhage. B ultrasonography showed an
      intermittently anechoic lesion that exhibits intrinsic flow during the Valsalva
      maneuver. Color Doppler imaging might demonstrate a reversal of flow toward the
      transducer during the Valsalva maneuver. Thirty-five of 43 cases with axial CT
      images showed a normal appearance or only mild enlargement of the involved veins,
      but coronal CT images could clearly demonstrate the lesion distensibility. Eight
      cases showed well defined tumor with homogeneous high density due to the
      thrombosis or hemorrhage within the orbit. MR imaging showed hypo to hyperintense
      signal on T(1)-weighted images, had hyperintense signal on T(2)-weighted MR
      images. However, signal of lesions of orbital hemorrhage could be various
      according to the different hemorrhage time. CONCLUSION: DOVM usually occurs in
      young patients. Clinical diagnosis can be established with the typical symptoms
      and one or more imaging examinations.

PMID- 23141507
TI  - [Reconstruction of blowout fractures of medial orbital walls].
AB  - OBJECTIVE: To explore the classification of medial orbital blowout fractures
      (OBF) and the applications of reconstruction materials, to evaluate the efficacy
      and safety of surgical orbital reconstruction. METHODS: A retrospective review of
      176 cases with medial OBF between January 2008 and January 2011 was conducted,
      they were classified to group I (pure medial wall fracture, 85 cases) and group
      II (combined medial and inferior walls fractures, 91 cases). Group I was
      classified into 3 subgroups, Ia, Ib, and Ic, according to the fractured
      appearances on CT scans. Group II was classified into 2 subgroups, IIa and IIb,
      according to the maxillo-ethmoidal bone buttress involved in or not. The
      operative designs and the choice of reconstruction materials were based on the
      fractured classification and diplopia. Materials used for repairing included
      artificial bone plates, titanium meshes and wedge implants. The surgical repairs
      were undergone via a trans-caruncular approach when necessarily combined with an
      inferior fornix or lower limbus palpebralis incision. Clinical outcomes and
      complications were recorded including visual acuity, exophthalmometry, diplopia,
      hypoglobus and CT scans before and follow-up period. RESULTS: Group II showed
      more significant enophthalmos than group I (-5.1 +/- 0.8 mm vs -2.7 +/- 0.7 mm, P
      = 0.000). Both groups improved after operations (group II: -5.1 +/- 0.8 mm vs. 
      0.7 +/- 1.2 mm, P = 0.000; group I: -2.7 +/- 0.7 mm vs. 0.1 +/- 0.8 mm, P =
      0.000). Ocular displacement was more common in group II than in group I (62% vs.
      0%, P = 0.000). The hypoglobus was more common in subgroup IIb than in IIa (71%
      vs. 38%, chi(2) = 8.19, P = 0.004) and significantly improved after operations in
      subgroup IIb (71% vs. 17%, chi(2) = 38.27, P = 0.000). Diplopia was more commonly
      noted in group II than in group I (100% vs. 83%, P = 0.000), and was
      significantly relieved in both groups (group I: Z = -4.475, P = 0.000; group II:
      Z = -9.751, P = 0.000). Postoperative CT displayed orbital walls reconstructed
      satisfyingly in 92%. No one was recorded with impaired vision after operation.
      The important complications were aggravated or new-onset diplopia, under- or over
      correction of enophthalmos and ocular superior displacement. CONCLUSIONS: A
      reconstructive operation of medial OBF with proper materials and surgical skills
      could be helpful for improving diplopia, enophthalmos and hypoglobus. The
      operations for repairing of medial OBF is efficient and safe.

PMID- 23141508
TI  - [Clinical features of blepharochalasis and surgical treatment of associated
      deformities].
AB  - OBJECTIVE: To describe the clinical features of blepharochalasis and the effect
      of surgical treatment of associated deformities. METHODS: A retrospective study
      reviewed 54 patients (98 eyes) with blepharochalasis. The main features analyzed
      included sex, age of onset, duration and clinical signs. Surgical treatment for
      the correction of deformities includes blepharoplasty; resuspension of the
      prolapsed lacrimal gland, ptosis repair, surgical correction of lower eyelid
      retraction and lateral canthoplasty. Follow-up ranged from 6 to 60 months.
      RESULTS: The average age of onset was 9.3 years. The duration in all 54 patients
      (32 females and 22 males) lasted for 2 - 16 years and different periorbital
      deformities were presented. After surgical repair, all patients were satisfied
      with their bilateral symmetrical creases in upper eyelids and the contour of
      upper eyelids. The appearance of floppy eyelids has been improved distinctly. The
      lateral canthus moved to the normal position. No patients complained epiphora or
      dry eye symptoms. Prolapse of the lacrimal gland recurred in two patients (three
      eyes). They underwent reoperation with no further recurrence. Overcorrection in
      blepharoptosis surgery of five patients was fixed with suture adjustment of the
      levator aponeurosis. CONCLUSIONS: Blepharochalasis onset often occurs around age
      10 years and stabilizes till adolescence. Since it involves bilateral or
      unilateral, local eye tissues or periorbital tissues, clinical manifestations may
      vary in blepharochalasis. Ophthalmic plastic surgery to correct blepharochalasis
      and its associated deformities in the quiescent stage is usually safe and with
      satisfactory cosmetic effects.

PMID- 23141509
TI  - [Clinical treatment for perforating injuries with foreign bodies located at
      posterior global wall].
AB  - OBJECTIVE: To describe the clinical features and surgical outcomes in a series of
      patients with perforating injuries and foreign bodies located at the exit wound
      in posterior global wall. METHODS: Retrospective case series of 17 eyes of 17
      patients were included in the study, each patient who received treatments between
      January 2006 and December 2010 had perforating injuries with foreign bodies
      located at posterior global wall. The exit wounds of perforating injuries were in
      the area of optic disc and macula in 8 eyes. Seventeen eyes had vitreous
      hemorrhage, 11 eyes had traumatic cataract, 8 eyes had retinal detachment and one
      eye had endophthalmitis. According to different therapeutic regimen, cases were
      divided into two groups. Group A (7 cases) underwent vitrectomy combined with
      extraction of foreign body as an emergency operation. Group B (10 cases)
      underwent extraction of foreign body as an emergency operation and secondary
      vitrectomy were performed 1 - 2 weeks later. The mean follow-up time was 18
      months (ranged from 9 - 47 months). The functional and anatomical results were
      compared between Group A and B. Fisher's exact test were used to analyze the
      data. RESULTS: The foreign bodies were extracted in 17 cases. Poor final best
      corrected visual acuity (BCVA) (worse than or equal to 0.1) was presented in all
      8 cases with the exit wound being in the area of optic disc and macula, but only
      in 4 of 9 cases with the exit wound located in other sites, the difference
      between these two groups was statistically significant (P = 0.029). At final
      follow-up, vision was improved in 5 cases from Group A and 7 cases from Group B
      (P = 1.000); BCVA were better than or equal to 0.1 in 4 cases from Group A and 3
      cases from Group B (P = 0.350) the differences were statistically nonsignificant.
      Intraoperative leakage at the exit wound occurred in 4 cases from Group A and one
      from Group B, the difference was statistically significant (P = 0.015).
      Intraoperative retinal detachment and postoperative silicone oil leakage occurred
      in 2 cases from Group A and none from Group B (P = 0.154). Postoperative retinal
      detachment occurred in 1 case from Group A and 3 cases from Group B (P = 0.603).
      Silicone oil-dependent eye occurred in 1 case from Group A and 2 cases from Group
      B (P = 1.000); the differences were statistically nonsignificant. CONCLUSIONS:
      The visual prognosis is worse in cases with the exit wound being in the area of
      optic disc and macula. Both therapeutic regimens were effective, but each has
      their pros and cons. Appropriate therapeutic regimen should be selected in term
      of situations. To avoid leakage at the exit wound in vitrectomy, we recommend
      therapeutic regimen B be selected first.

PMID- 23141510
TI  - [Clinical analysis of long term safety after implantation of iris-fixed phakic
      intraocular lens Verisyse].
AB  - OBJECTIVE: To analyze the long-term safety of implantation of iris-fixed phakic
      intraocular lens (IOL) Verisyse for the treatment of high myopia. METHODS: One
      hundred and eighteen eyes of 59 cases implanted Verisyse for high myopia in Eye
      Center of Tongren Hospital from Jan. 2005 to Jan. 2007 were followed up for 48 to
      72 months, mean time period was (56.2 +/- 16.9) months. There were 32 male cases
      (64 eyes) and 27 female cases (54 eyes). Age ranged from 22 to 39 years old, mean
      (26.6 +/- 7.5) years. The uncorrected vision acuity was 0.02 - 0.08, and the best
      corrected vision acuity was 0.3 - 1.0. The visual acuity, refraction, intraocular
      pressure, corneal endothelium and the distance between Verisyse to corneal and
      lens was measured separately, and the complications were also observed. The
      results were treated with analysis of paired-samples t test and Fisher exact
      probability test. A difference at P < 0.05 was considered to be statistically
      significant. RESULTS: The complications included the dislocation of Verisyse into
      anterior chamber in 8 cases (8 eyes, 6.78%), retina detachment in 2 cases (2
      eyes, 1.69%), corneal endothelium lost more than 1000/mm(2) in 6 cases (7 eyes,
      5.93%), corneal edema in 1 case (1 eye, 0.84%). Pre-operative mean corneal
      endothelium density was (2821 +/- 117)/mm(2), and it was (2249 +/- 654)/mm(2)
      after surgery. There was no significant difference (t = 1.112, P = 0.09) between
      pre- and post-operative data. Post-operative uncorrected vision improved 5 to 8
      lines than that of pre-operation. Post-operative corrected vision improved 1 to 3
      lines than that of pre-operation except 1 case (1 eye) developed corneal
      decompensation and 2 cases (2 eyes) developed retina detachment. SE showed no
      significant difference in long-term after operation compared with 3 months after
      surgery (t = 0.641, P = 0.21). The mean intraocular pressure was (16.4 +/- 3.4)
      mm Hg (1 mm Hg = 0.133 kPa). The distance between anterior surface of IOL and
      endothelium was (2.468 +/- 0.342) mm, distance between posterior surface of IOL
      and lens was (0.652 +/- 0.176) mm, and distance between edge of IOL and
      peripheral endothelium was (1.728 +/- 0.213) mm except eyes occurred Verisyse
      dislocation. Verisyse dislocation occurred more commonly when the iris was not
      perfectly crapped in the loop, and the difference was significant (P = 0.000). No
      glaucoma occurred. CONCLUSIONS: Implantation of Verisyse can correct high myopia
      effectively. But it damages corneal endothelium in some cases. This complication
      may be related to the unstable position of Verisyse in the anterior chamber. So
      we should pay more attention to the safety of this kind of phakic IOL clinically.

PMID- 23141511
TI  - [Gene mapping and analysis of candidate genes in a Chinese family with autosomal
      dominant congenital coralliform cataract].
AB  - OBJECTIVE: To map and to identify the causal gene of autosomal dominant
      congenital coralliform cataract (ADCC) in a Chinese family. METHODS: Case series
      study. Clinical features of all affected members in this family were examined.
      Blood samples were collected from nine family members for genetic linkage
      analysis. Polymorphic microsatellite markers were selected from the regions which
      harbor all known loci linked with ADCC. Direct genomic sequencing was used to
      evaluate the candidate gene. RESULTS: The affected members in this family showed
      classic phenotype of ADCC. The maximum two-point LOD score of 1.51 was obtained
      for marker D2S325 (theta = 0). The LOD score of 1.20 was obtained for marker
      D11S925. The CRYGC/CRYGD gene located on 2q33-q35 and the CRYAB gene located on
      11q22-q22.3. Therefore, the CRYGC/CRYGD and CRYAB gene may be the candidate gene
      in this family. Sequencing of the coding regions of the CRYGD gene showed the
      presence of a heterozygous C->A transversion at nucleotide 70 in exon 2 of CRYGD
      that is associated with cataracts in this family. This mutation resulted in a
      proline to threonine substitution at amino acid 23 of the protein in the first of
      the four Greek key motifs that characterized this protein. No mutation in all
      exons of CRYGC and CRYAB gene were found in the family. CONCLUSION: Direct DNA
      sequence analysis revealed a C-to-A transition at nucleotide 70 of the CRYGD gene
      in this ADCC family.

PMID- 23141512
TI  - [Spectral domain optical coherence tomography to assess the association between
      the inner caliber of large retinal vessel and the primary hypertension].
AB  - OBJECTIVE: To assess the inner caliber of large retinal vessel quantitatively
      using spectral domain optical coherence tomography (SD-OCT) and to reveal the
      association between changes in the inner caliber of large retinal vessel and the
      primary hypertension. METHODS: A retrospective case-control study was carried out
      including 215 cases (with primary hypertension) and 210 controls (without primary
      hypertension) admitted to our hospital since 2009 and all the cases and controls
      were grouped according to age. SD-OCT was performed to assess the inner caliber
      of large retinal vessel quantitatively including retinal artery inner caliber
      (RAIC), retinal vein inner caliber (RVIC) and retinal arterio-venous inner
      caliber ratio (RAVICR). The differences in the inner caliber of large retinal
      vessel between the cases and the controls in each age groups were analyzed by t
      test. In all cases, multiple comparisons were performed according to their blood
      pressure level by SNK test of one way ANOVA. The RAVICR was also correlated with
      the following relevant determinants via multiple stepwise regression analysis:
      age, diastolic and systolic blood pressure. RESULTS: In each age group of cases
      (< 40, 40 to 49, 50 to 59, 60 to 69, >= 70 years), the values of RAIC were (93.0
      +/- 6.3), (86.2 +/- 6.1), (84.5 +/- 5.1), (84.0 +/- 5.5), and (81.7 +/- 5.4) um
      respectively, and the values of RVIC were (129.4 +/- 5.8), (130.7 +/- 6.5),
      (129.6 +/- 5.4), (132.2 +/- 6.4), and (131.6 +/- 5.1) um respectively, and the
      values of RAVICR were (0.720 +/- 0.07), (0.661 +/- 0.06), (0.653 +/- 0.04),
      (0.637 +/- 0.06), and (0.621 +/- 0.05) um respectively. Compared with controls,
      RAIC (t = -4.813, -10.893, -15.689, -8.811, and -10.151 respectively; P < 0.05)
      and RAVICR (t = -3.276, -8.654, -13.470, -7.801, and -9.210 respectively; P <
      0.05) were significantly decreased in each age group of cases. Multiple
      comparisons were made among each systolic and diastolic pressure groups in all
      cases. In systolic groups, difference of RAIC or RAVICR were significant (SNK
      test)between 140 to 149 mm Hg (1 mm Hg = 0.133 kPa) and 170 to 179 mm Hg group (q
      = 9.46, 10.61; P < 0.05), 140 to 149 mm Hg and >= 180 mm Hg group (q = 11.03,
      13.98; P < 0.05), 150 to 159 mm Hg and 170 to 179 mm Hg group (q = 8.13, 8.82; P
      < 0.05), 150 to 159 mm Hg group and >= 180 mm Hg group (q = 9.01, 9.97; P <
      0.05). In diastolic groups, difference of RAIC or RAVICR were significant (SNK
      test) between 90 to 99 mm Hg and 100 to 109 mm Hg group (q = 6.79, 5.95;P <
      0.05), 90 to 99 mm Hg and >= 110 mm Hg group (q = 9.72, 10.21; P < 0.05), 100 to
      109 mm Hg and >= 110 mm Hg group (q = 5.93, 6.07; P < 0.05). RAVICR was
      associated with the diastolic and systolic blood pressure revealed by the
      multiple stepwise regression analysis (ANOVA: F = 11.231; Standardized regression
      coefficient: beta = -0.024, -0.019, respectively; P < 0.05). CONCLUSIONS:
      Quantitative assessment for the inner caliber of large retinal vessel can be done
      by SD-OCT. The value of RAI and RAVICR were correlated with diastolic and
      systolic blood pressure in primary hypertension.

PMID- 23141513
TI  - [Analysis of anatomy features for patients with narrow anterior chamber angle and
      primary iridociliary body cysts].
AB  - OBJECTIVE: To investigate the prevalence and anatomy features of iridociliary
      body cysts in patients with narrow anterior chamber angle. METHODS: Retrospective
      case series study. The prevalence and anatomy features of iridociliary body cysts
      in 223 patients (402 eyes) were analyzed retrospectively with ultrasound
      biomicroscopy (UBM). All of the patients were examined for susceptive narrow
      anterior chamber angle without complaint. The age of the patients, the site,
      diameter and number of cysts, the anterior chamber angle and the central anterior
      chamber depth were measured. RESULTS: Iridociliary body cysts were found in 19
      patients (23 eyes) out of 223 patients (402 eyes), the prevalence is 5.7%.
      Fifteen patients were unilateral and four patients bilateral. Two cases
      originated from the ciliary process, eighteen cases from the iris root, and three
      from both the root and posterior surface of the iris. Twenty one cases were
      single cysts while two cases were multiple cysts. The diameter of the cysts
      ranged from 0.5 to 3.1 mm, averaged (0.71 +/- 0.53) mm. The average age and the
      central anterior chamber depth of the eyes with iridociliary body cysts were
      (55.32 +/- 10.74) years and (2.25 +/- 0.39) mm, with no significant difference (t
      = 0.534, 0.783; P > 0.05) as compared to that of patients without cysts, which
      were (57.46 +/- 10.52) years and (2.14 +/- 0.34) mm. The anterior chamber angle
      in iridociliary body cysts group was 8.2 degrees  (21.0 degrees , 0.0 degrees ),
      with no significant difference (Z = -0.062, P > 0.05) as compared to that of
      patients without cysts, which was 8.9 degrees  (21.4 degrees , 0.0 degrees ).
      CONCLUSIONS: The prevalence rate of iridociliary body cysts in this study is
      5.7%, central anterior chamber depth and anterior chamber angle in patients with
      cysts do not differ form patients without cysts.

PMID- 23141514
TI  - [Recurrent N1173K mutation in FBN1 gene in a Chinese family with ectopia lentis].
AB  - OBJECTIVE: To study the disease-causing gene mutation in a Chinese family with
      ectopia lentis. METHODS: The phenotype of each family member in a Chinese family
      with ectopia lentis was identified by detailed clinical examination. The
      inheritance mode in this family was ascertained by the pedigree analysis. Linkage
      analysis was performed by microsatellite markers on chromosome 15 and LOD Score
      was calculated by Mlink program. Gene mutations were detected by sequence
      analysis to the whole coding region and exon-intron boundaries of the candidate
      gene. RESULTS: A significant LOD score of 3.01 was obtained at D15S978 on
      chromosome 15q21.1, where FBN1 gene was located. A C3519G change in exon 29 of
      FBN1 gene, resulting in asparagine change to lysine at codon 1173, was detected
      by direct sequence analysis. This mutation was absent in the normal family
      members and 100 normal controls. CONCLUSIONS: Our results indicate that c.C3519G
      (p.N1173K) mutation in FBN1 gene is the underlying molecular pathogenesis of this
      family with ectopia lentis.

PMID- 23141515
TI  - [Investigation of the role of mesenchymal stem cells on keratoplasty rejection].
AB  - OBJECTIVE: To investigate the effect of mesenchymal stem cells (MSC) on
      keratoplasty rejection in a rat mode. METHODS: MSC from bone marrow of Wistar
      rats was cultured. Corneas of Wistar rats (donors) were transplanted to Lewis
      rats (recipients). Transplanted rats were randomly divided into A, B, C three
      groups. Rats in group B were injected with MSC suspended in PBS via the tail vein
      continually for three days before the surgery, while rats in group C accepted
      similar MSC transplantation after the surgery. The rats in group A were given the
      same volume of PBS. Grafts were scored for corneal transparency, edema and extent
      of neovascularization by slit lamp observation. Expressions of CD(4), CD(8),
      CD(25) and CD(45) in corneas 10 days after transplantation were examined by
      immunohistochemistry. RESULTS: The survival time of the corneal grafts in group C
      [(9.9 +/- 0.69) d] was significantly prolonged compared with that of the group A
      and group B [(11.83 +/- 0.54), (16.89 +/- 1.91) d] (F = 5.732, P = 0.001, 0.019).
      Expression level of CD(4), CD(8), CD(25) of the corneal grafts in group C was
      lower than that of group A and group B (t = 2.477, 2.359, 2.445, P = 0.024,
      0.042, 0.030). CONCLUSION: Post-operative injection of MSCs could inhibit
      keratoplasty rejection and prolong the corneal allografts survival in a rat
      model.

PMID- 23141516
TI  - [Protective effect of valproic acid on ischemia-reperfusion induced injury in
      retina of rat].
AB  - OBJECTIVE: To study the protective effects and the related mechanism of valproic
      acid (VPA) on ischemia-reperfusion-induced injury in retina of rat. METHODS:
      Experimental study. Ninety Wistar rats were divided randomly into three groups:
      normal (blank) control group, retinal ischemia-reperfusion (experimental control)
      group treated with PBS, retinal ischemia-reperfusion (experimental) group treated
      with VPA. Retinal ischemia was induced by acute high intraocular pressure. Rats
      were executed at 6, 12, 24, 48 h and 7 d after reperfusion. The eyeballs were
      enucleated for retinal histopathological examination. The fluoro-gold retrograde
      labeling was performed and the survival of retinal ganglion cells was analyzed by
      calculating the densities in fluoro-gold labeled retinal ganglion cell. The
      protein expression of heat shock protein 70 (Hsp70) and the acetylation of
      transcription factor Sp1 were analyzed by Western blot assay. The levels of bcl-2
      and bax mRNA were analyzed by RT-PCR assay. To determine the significance of
      differences, analysis of paired-samples t-test was carried out. RESULTS: (1) The
      HE staining of retinal histological section showed that the edema of retina were
      attenuated significantly by VPA in experimental group, the difference between the
      experimental group and the experimental control group was statistically
      significant (t = 7.491, P < 0.05). The fluoro-gold retrograde labeling showed
      that the survival of retinal ganglion cells in experimental group [(1629 +/-
      63)/mm(2)] was significantly higher than experimental group [(908 +/- 65)/mm(2)],
      the difference between the two groups was statistically significant (t = 7.248, P
      < 0.05). (2) The immuno-blot analysis showed that VPA resulted in significant
      increase in expression of Hsp70 protein in ischemic retinas, the difference
      between experimental group and experimental control group was statistically
      significant (t = 6.176, P < 0.05). The acetylation of Sp1 was significantly
      higher in experimental group than experimental control group, the difference
      between the two groups was statistically significant (t = 11.264, P < 0.05). The
      RT-PCR analysis showed that VPA increased the expression of bcl-2 mRNA in
      experimental group (0.403 +/- 0.009), the difference between experimental group
      and experimental control group (0.314 +/- 0.012) was statistically significant (t
      = 5.489, P < 0.05). VPA attenuated the expression of bax mRNA in experimental
      group (0.383 +/- 0.009), the difference between experimental group and
      experimental control group (0.492 +/- 0.016) was statistically significant (t =
      5.723, P < 0.05). CONCLUSIONS: (1) VPA protected retina from ischemic injury. (2)
      The upregulation of Hsp70 and bcl-2, downregulation of bax maybe involved in the
      mechanism of the protection.

PMID- 23141517
TI  - [Effects of matrix metalloproteinases inhibitor GM6001 on choroidal
      neovascularization].
AB  - OBJECTIVE: To explore the efficiency of GM6001 for the inhibition of choroidal
      neovascularization. METHODS: Experimental study. Twenty-four Brown Norvy (BN)
      rats after photocoagulation were randomly divided into 3 groups as GM6001 group,
      DMSO group and CONT group. GM6001 (0.2 ml of 0.1% suspension) was injected
      retrobulbar for GM6001 group and 0.2 ml DMSO was injected for DMSO group on days
      1, 3, 6, 9, and 12 after photocoagulation. No injection was performed in the CONT
      group. Fundus fluorescence angiography, histopathology, immunohistochemistry and
      quantitative analysis of choroidal neovascularization (CNV) were performed 3
      weeks after photocoagulation. One-way ANOVA was used in conjunction with SNK-t
      test to assess statistical significance within groups. RESULTS: The fluorescein
      leakage appeared in all three groups; but fluorescein leakage of GM6001 group
      (74.56 +/- 2.33) was less than that of DMSO group (119.57 +/- 1.15)and CONT group
      (122.36 +/- 2.38) (F = 403.23, P = 0.001; LSD-t test, all P value < 0.01),
      whereas fluorescein leakage of DMSO group was similar to that in the CONT group.
      The retinal and choroidal capillaries in the CONT group were damaged and
      disordered; a great deal of CNV and migration and proliferation of retinal
      pigment epithelium cells, fibrocytes and collagen fibers were discovered.
      Pathological changes in DMSO group were similar to those in the CONT group. There
      were a small quantity of retinal pigment epithelium cells, fibrocytes and CNV in
      GM6001 group. Although the immunohistochemical staining for CD105 displayed
      positive results in all three groups, positive staining of GM6001 group (19.85 +/
      1.59) was significantly less than that of the CONT group (38.02 +/- 2.57) and
      DMSO group (39.02 +/- 3.12) (F = 55.57, P = 0.001; LSD-t test, all P value <
      0.01). Positive staining of CD105 in the CONT group was similar to that of DMSO
      group (P > 0.05). The size of CNV in GM6001 group (15.35 +/- 0.77) was
      significantly less than that of CONT group (28.38 +/- 1.60) and DMSO group (28.74
      +/- 1.19) (F = 114.85, P = 0.001; LSD-t test, all P value < 0.01). There was no
      statistical difference for the size of CNV between CONT group and DMSO group (P >
      0.05). CONCLUSION: GM6001 effectively inhibits CVS induced by krypton laser
      photocoagulation.

PMID- 23141518
TI  - [Progress on study of achromatopsia and targeted gene therapy].
AB  - Achromatopsia is an early onset retinal dystrophy that causes severe visual
      impairment. To date, four genes have been found to be implicated in achromatopsia
      associated mutations: guanine nucleotide-binding protein (GNAT2), cyclic
      nucleotide-gated channel alpha-3 (CNGA3), cyclic nucleotide-gated channel beta-3
      (CNGB3) and phosphodiesterase 6C (PDE6C). Even with early onset, the slow
      progress and the good responses to gene therapy in animal models render
      achromatopsia a very attractive candidate for human gene therapy after the
      successful of the Phase I clinical trials of Leber's congenital amaurosis. With
      the development of molecular genetics and the therapeutic gene replacement
      technology, the adeno-associated viral (AAV) vector-mediated gene therapy for
      achromatopsia in the preclinical animal experiments achieved encouraging progress
      in the past years. This article briefly reviews the recent research achievements
      of achromatopsia with gene therapy.

PMID- 23141519
TI  - [Research of eye diseases associated with PERK mediated endoplasmic reticulum
      stress].
AB  - Endoplasmic reticulum is the organelle where proteins get folded and assembled,
      and all kinds of damage factors can lead to the accumulation of unfolded
      proteins, therefore initiate endoplasmic reticulum stress (ERS) by activating the
      intracellular signal transduction pathways-cumulatively called the unfolded
      protein response, either to protect cells or to induce cell apoptosis. PERK
      pathway has been considered as a main signal transduction pathway of ERS, and a
      lot of eye diseases are correlated with PERK pathway mediated ERS. This article
      mainly summarize the progress of the eye diseases associated with PERK pathway
      mediated ERS.

PMID- 23141520
TI  - The influence of dexamethasone administration on the protection against
      doxorubicin-induced cardiotoxicity in purified embryonic stem cell-derived
      cardiomyocytes.
AB  - Embryonic stem cells (ESCs) have various uses in drug toxicity, as they can be
      easily differentiated in vitro. However, one of the major obstacles in the
      assessment of these differentiated cells is the presence of a heterogeneous cell
      population. To circumvent this problem, purified ESC-derived desired cells by
      means of the tissue-specific GFP and/or antibiotic resistance gene expression has
      been proposed. Therefore, this study aimed to assess the role of doxorubicin
      (DOX) in cardiotoxicity by using genetically engineered purified ESC-derived
      cardiomyocytes under the control alpha-myosin heavy chain promoter. The results
      revealed that ESCs are suitable for evaluation of DOX cardiotoxicity. This study
      showed that DOX cardiotoxicity was reduced as detected by beating cardiomyocytes
      and caspase activity only by pretreatment with dexamethasone (DEX), not during or
      post-DOX treatment. DEX influence appears to be mediated via glucocorticoid
      receptor and enhances cardiomyocyte-specific gene expression. Therefore, for the
      general assessment of cytotoxicity, non-genetically engineered ESC-derived
      cardiomyocytes are sufficient but for the molecular assessment of DOX-induced
      toxicity, genetically engineered purified ESC-derived cardiomyocytes are
      necessary.

PMID- 23141521
TI  - Biaxial and failure properties of passive rat middle cerebral arteries.
AB  - Rodents are commonly used as test subjects in research on traumatic brain injury
      and stroke. However, study of rat cerebral vessel properties has largely been
      limited to pressure-diameter response within the physiological loading range. A
      more complete, multiaxial description is needed to guide experiments on rats and
      rat vessels and to appropriately translate findings to humans. Accordingly, we
      dissected twelve rat middle cerebral arteries (MCAs) and subjected them to
      combined inflation and axial stretch tests around physiological loading
      conditions while in a passive state. The MCAs were finally stretched axially to
      failure. Results showed that MCAs under physiological conditions were stiffer in
      the axial than circumferential direction by a mean (+/-standard deviation) factor
      of 1.72 (+/-0.73), similar to previously reported behavior of human cerebral
      arteries. However, the stiffness for both directions was lower in rat MCA than in
      human cerebral arteries (p<0.01). Failure stretch values were higher in rat MCA
      (1.35+/-0.08) than in human vessels (1.24+/-0.09) (p=0.003), but corresponding
      1st Piola Kirchhoff stress values for rats (0.42+/-0.09 MPa) were considerably
      lower than those for humans (3.29+/-0.64 MPa) (p<0.001). These differences
      between human and rat vessel properties should be considered in rat models of
      human cerebrovascular injury and disease.

PMID- 23141522
TI  - Effect of estrogen deficiency on regional variation of a viscoelastic tissue
      property of bone.
AB  - Estrogen deficiency changes the regional distribution of tissue mineral density
      leading to alteration of the mechanical properties of bone at the tissue level.
      Direct measurement of the regional variation of elastic modulus and viscosity,
      which is the capacity to resist time-dependent viscoelastic deformation, will aid
      in our understanding of how estrogen deficiency alters bone quality. It was
      observed that, compared to bone from other anatomical sites, the jaw bone is less
      sensitive to estrogen deficiency. Thus, the objective of this study was to
      examine the effect of estrogen deficiency on (1) the regional variations of
      tissue modulus and viscosity of bone using nanoindentation, and (2) the modulus
      viscosity relationships in jaw and vertebral bones for comparison between
      different anatomical sites. Mandibular and vertebral bone specimens of sham
      surgery and ovariectomized (OVX) rat groups were subject to nanoindentation in
      hydration. Indentation modulus and viscosity were measured at relatively new
      (less mineralized) tissue regions and at the corresponding pre-existing old (more
      mineralized) tissue regions of mandibular and vertebral bones. In the mandibular
      bones, significant regional variations of indentation modulus and viscosity were
      observed (p<0.039) and OVX increased the indentation viscosity. While significant
      positive correlations were found between indentation modulus and viscosity
      (p<0.001), the correlation slopes for the mandibular and vertebral bones were
      significant different (p<0.001). The current results indicated that changes in
      viscoelastic property and its regional variation should be examined to obtain a
      better understanding of estrogen deficiency-dependent alteration of bone quality.

PMID- 23141523
TI  - Relationships between clinical characteristics and nocturnal cardiac autonomic
      activity in Parkinson's disease.
AB  - BACKGROUND: The aim of the present study was to explore the association between
      Parkinson's disease (PD) clinical characteristics and cardiac autonomic control
      across sleep stages. METHODS: Frequency-domain heart rate variability (HRV)
      measures were estimated in 18 PD patients undergoing a night of polysomnography.
      RESULTS: Significant relationships were found between PD severity and nocturnal
      HRV indices. The associations were restricted to rapid eye movement (R) sleep.
      CONCLUSIONS: The progressive nocturnal cardiac autonomic impairment occurring
      with more severe PD can be subclinical emerging only during conditions requiring
      active modulation of physiological functions such as R-sleep.

PMID- 23141524
TI  - The new nitric oxide donor 2-nitrate-1,3-dibuthoxypropan alters autonomic
      function in spontaneously hypertensive rats.
AB  - Previously, we found that the nitrate synthesized from glycerin, 2-nitrate-1,3
      dibuthoxypropan (NDBP), increased NO levels in rat aortic smooth muscle cells,
      inducing vasorelaxation in mesenteric artery. However, its effects on blood
      pressure and heart rate as well as on autonomic function were not investigated.
      This study evaluated the action of NDBP on these cardiovascular parameters in
      spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats. We found that NDBP
      causes a biphasic response: hypotension and bradycardia followed by hypertension
      and tachycardia in WKY and SHR rats. Atropine (2mg/kg) blunted the hypotension
      induced by NDBP (15 mg/kg) in WKY and SHR (-75 +/- 9 vs -12 +/- 3 mmHg, n=6; -101
      +/- 6 vs -7 +/- 2 bpm, n=6; respectively, p<0.05) and the pressor response to the
      compound was potentiated. Furthermore, vagotomy reduced the bradycardia in WKY
      and SHR (-136 +/- 8 vs -17 +/- 2, n=4, p<0.05; -141 +/- 9 vs -8 +/- 2, n=6,
      p<0.05). Moreover, hexamethonium (30 mg/kg) reduced both bradycardia (-278 +/- 23
      vs -48 +/- 3 in WKY; -285 +/- 16 vs -27 +/- 19 in SHR, n=4; p<0.05) and pressor
      response (28 +/- 8 vs -9 +/- 5-WKY, n=6; 42 +/- 7 vs -19 +/- 8-SHR, n=5; p<0.05).
      In addition, administration of methylene blue (4 mg/kg) attenuated the
      hypotensive and bradycardic responses to the NDBP in all groups. In conclusion,
      NDBP induces bradycardia by direct vagal stimulation and pressor response by
      increasing sympathetic outflow to the periphery.

PMID- 23141525
TI  - Ultrastructure of female accessory glands in the scorpionfly Panorpa sexspinosa
      Cheng (Mecoptera: Panorpidae).
AB  - The histology and ultrastructure of the female accessory glands in the
      scorpionfly Panorpa sexspinosa Cheng was studied using light and transmission
      electron microscopy. The glands consist of a pair of distal elongate gland tubes
      and a basal common duct, which opens in the genital cavity at the dorsal side of
      the genital plate. The whole gland tubes and common duct are similar
      histologically and ultrastructurally. The epithelium of female accessory glands
      consists of two cell types: the outer secretory cells and the inner duct-forming
      cells. These two cells that join with a cuticular duct connecting to the inner
      intima constitute a functional glandular unit belonging to Class 3 glandular
      cells of epidermal glands. The secretory cells are rich in organelles, such as
      mitochondria, rough endoplasmic reticulum, and Golgi complex, indicating that
      they are active in secretion. The duct-forming cells are flattened with sparse
      distributed organelles. These two kinds of cells are connected by septate
      junctions. The cuticular duct consists of a receiving and a conducting canal and
      is responsible for transferring the secretions of the secretory cell to the
      lumen. The receiving canal is formed of interrupted multilayered inner epicuticle
      and located in the irregular extracellular cavity of the secretory cell, bounded
      by microvilli. The conducting canal connects the inner intima and opens into the
      central lumen. The tentative functions of the secretions are briefly discussed.

PMID- 23141526
TI  - Prophylactic magnesium does not prevent atrial fibrillation after cardiac
      surgery: a meta-analysis.
AB  - BACKGROUND: Atrial fibrillation (AF) is a common complication after cardiac
      surgery. Previous meta-analyses have concluded prophylactic magnesium (Mg)
      prevents postoperative AF, although with a significant degree of heterogeneity
      among included studies. Recently, the largest randomized, controlled trial
      published to date (but not included in prior published meta-analyses) concluded
      that Mg sulfate is not protective against AF after cardiac surgery. The objective
      of this study was to conduct a new meta-analysis including the results of new Mg
      trials not included in previous meta-analyses, and to investigate the potential
      causes and effects of significant heterogeneity observed in previously published
      meta-analyses. METHODS: The MEDLINE, EMBASE, and CENTRAL databases were searched
      for relevant studies published up to March 31, 2012. Pooled odds ratios of
      occurrence of AF were calculated using random-effects models. Heterogeneity was
      assessed as significant using the I(2) statistic. RESULTS: Egger's and funnel
      plots demonstrated biases toward stronger and more positive effects of Mg in
      smaller studies. When the analysis was restricted to the five double-blind,
      intention-to-treat studies in which AF was the primary outcome (Mg arm, n = 710;
      control arm, n = 713), Mg did not prevent postoperative AF (odds ratio, 0.94; p =
      0.77), and heterogeneity was no longer significant (I(2) = 40%; p = 0.15).
      CONCLUSIONS: This meta-analysis, restricted to well-conducted trials, does not
      support the prophylactic use of Mg to prevent AF after cardiac surgery. Prior
      meta-analyses have drawn conclusions from simple random-effects models with
      significant heterogeneity. However, this approach leaves important residual
      heterogeneity and overemphasizes the strongly positive effects of smaller
      studies.

PMID- 23141527
TI  - Transcatheter aortic valve implantation in very high-risk patients with EuroSCORE
      of more than 40%.
AB  - BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a new method for
      the treatment of high-risk patients with aortic valve stenosis. Although a
      logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) of
      more than 40% has been considered a contraindication for this new procedure, we
      routinely perform this procedure in this very high-risk patient group. We
      analyzed the results of TAVI patients with a EuroSCORE of over 40%. METHODS:
      Between April 2008 and January 2012, 514 consecutive patients underwent TAVI. In
      the study group (group I, EuroSCORE > 40%) of 186 patients the EuroSCORE was 63%
      +/- 16% (range 40 to 98) and the Society of Thoracic Surgeons predicted risk of
      mortality score was 23% +/-14% (range 4 to 90); there were 26 (14%) patients in
      cardiogenic shock. The mean age was 81 +/- 8 (range 36 to 99) years and there
      were 122 women and 64 men. Group II (the control group, EuroSCORE < 40%)
      consisted of 328 patients. In this group the EuroSCORE was significantly lower
      (23% +/- 9%, range 2% to 40%). The STS mortality score was 11% +/- 8% (1% to
      48%). In this group were 196 men and 132 women with a mean age of 78 +/- 8 (range
      29 to 97) years. RESULTS: Technically, in group I the valve was successfully
      implanted in 99.5% (185 of 186). In 25 (13%) patients the procedure was performed
      on the heart-lung machine and in 25 (13%) patients an elective percutaneous
      coronary intervention was performed in the same session. Postoperative
      echocardiography showed a low transvalvular gradient (mean 4.5% +/- 2.5%, range 2
      to 15) and a low rate of paravalvular regurgitation (grade 0 in 97, less than
      grade I in 49, less than grade II in 38 patients, and grade II in 2 patients).
      The overall 30-day mortality in patients with EuroSCORE of over 40% (group I),
      including that in patients in cardiogenic shock, was 6.5%, and in patients with
      EuroSCORE of over 40% (group I) and without cardiogenic shock it was 5.7%; the 1
      year survival was 67% and 71%, respectively, and the 2-year survival was 54% and
      56%, respectively. CONCLUSIONS: Patients with comorbidities, as mirrored by a
      EuroSCORE of more than 40% should not be refused for TAVI. On the contrary, this
      is a supreme indication for the TAVI procedure.

PMID- 23141528
TI  - Effects of targeted papillary muscle relocation on mitral leaflet tenting and
      coaptation.
AB  - BACKGROUND: Ischemic mitral valve (MV) repair for patients with severe left
      ventricular dilation remains challenging. The objective of this study was to
      investigate the efficacy of papillary muscle (PM) relocation to restore
      physiologic MV function. METHODS: Fresh ovine MVs (n = 6) were studied in a left
      heart simulator under physiologic hemodynamics. Ischemic MV disease was simulated
      by annular dilation and PM displacement. Initial valvular repair was performed
      with mitral annuloplasty; further PM displacement simulated progressive left
      ventricular dilation. Basal PM repositioning (Kron procedure), performed to
      alleviate leaflet tethering, consisted of relocating (1) both PMs toward the
      commissures; (2) both PMs toward the trigones; (3) the posteromedial PM toward
      the ipsilateral commissure; and (4) the posteromedial PM toward the ipsilateral
      trigone. Coaptation length and tenting area were measured using three-dimensional
      echocardiography as surrogates of MV function. RESULTS: Papillary muscle
      relocation as an adjunct to mitral annuloplasty statistically improved coaptation
      length and tenting area compared with the disease condition. No statistical
      differences in coaptation length and tenting area were observed between final
      repaired conditions and control conditions. No statistical differences were
      observed between commissural and trigonal repairs at any incremental repair step.
      Coaptation length and tenting area were plotted against PM distance; the data
      were fit to linear regressions. CONCLUSIONS: In a realistic in vitro model of
      ischemic left ventricular dilation, apical-basal PM relocation, as an adjunct
      procedure to mitral annuloplasty, restored optimal MV closure. Trigonal or
      commissural traction suture location did not significantly affect the degree of
      restored coaptation. Linear relationships between PM positions and leaflet
      variables were established, which could be used to inform surgical repairs.

PMID- 23141529
TI  - Thymic carcinoma: a multivariate analysis of factors predictive of survival in
      290 patients.
AB  - BACKGROUND: Thymic carcinoma is a rare, aggressive disease with low 5-year
      survivals. We undertook this study to identify factors that impact prognosis and
      to better define the relationship between survival and surgical intervention.
      METHODS: We queried the Surveillance, Epidemiology, and End Results cancer
      database and identified patients with thymic carcinoma. We performed univariate
      and multivariate analyses to identify factors prognostic for survival, focusing
      on demographic, tumor, and treatment variables. RESULTS: For 290 patients with
      thymic carcinoma, the median survival was 48 months with 5-year survival of 30%.
      In multivariate analysis, type of surgical therapy (none, incomplete excision,
      complete thymic excision, debulking), Masaoka stage, and sex were important
      determinants of survival. Patients who underwent complete thymic excision had a
      significantly longer median survival than those who did not receive surgical
      therapy (105 versus 29 months; p < 0.001). In patients who underwent complete
      thymic excision, Masaoka stage and race were important determinants of survival
      in multivariate analysis. CONCLUSIONS: Complete thymic excision is the preferred
      primary treatment for thymic carcinoma. Masaoka stage has significant prognostic
      implications for all patients, including those who undergo complete thymic
      excision.

PMID- 23141530
TI  - Hsp104 gives clients the individual attention they need.
AB  - Yeast heat shock protein 104 (Hsp104), the only known eukaryotic disaggregase,
      remodels both disordered protein aggregates and cross-beta sheet amyloids. To
      handle this diverse clientele, DeSantis et al. report that Hsp104 hexamers use
      distinct mechanisms-individual subunits are able to dissolve disordered
      aggregates, but global subunit cooperativity is required to untangle amyloids.

PMID- 23141531
TI  - TTBK2 kinase: linking primary cilia and cerebellar ataxias.
AB  - Mutations disrupting primary cilia cause retinal, renal, and cerebellar defects,
      and misregulated Sonic hedgehog signaling. A new mouse mutant in the TTBK2 kinase
      fails to make cilia, and shows neural tube and Sonic hedgehog signaling defects.
      Ciliary targeting mutations in human TTBK2 are linked to spinocerebellar ataxia,
      suggesting cilia protect from neurodegeneration.

PMID- 23141532
TI  - Capturing the cloud: UAP56 in nuage assembly and function.
AB  - The nuage is a hazy electron-dense structure unique to germ cells and is enriched
      in components of the piRNA pathway. Although the nuage is cytoplasmic, Zhang et
      al. now show that it is organized by an intranuclear protein, UAP56.

PMID- 23141533
TI  - Daddy issues: paternal effects on phenotype.
AB  - The once popular and then heretical idea that ancestral environment can affect
      the phenotype of future generations is coming back into vogue due to advances in
      the field of epigenetic inheritance. How paternal environmental conditions
      influence the phenotype of progeny is now a tractable question, and researchers
      are exploring potential mechanisms underlying such effects.

PMID- 23141534
TI  - Pathogenic SYNGAP1 mutations impair cognitive development by disrupting
      maturation of dendritic spine synapses.
AB  - Mutations that cause intellectual disability (ID) and autism spectrum disorder
      (ASD) are commonly found in genes that encode for synaptic proteins. However, it
      remains unclear how mutations that disrupt synapse function impact intellectual
      ability. In the SYNGAP1 mouse model of ID/ASD, we found that dendritic spine
      synapses develop prematurely during the early postnatal period. Premature spine
      maturation dramatically enhanced excitability in the developing hippocampus,
      which corresponded with the emergence of behavioral abnormalities. Inducing
      SYNGAP1 mutations after critical developmental windows closed had minimal impact
      on spine synapse function, whereas repairing these pathogenic mutations in
      adulthood did not improve behavior and cognition. These data demonstrate that
      SynGAP protein acts as a critical developmental repressor of neural excitability
      that promotes the development of life-long cognitive abilities. We propose that
      the pace of dendritic spine synapse maturation in early life is a critical
      determinant of normal intellectual development.

PMID- 23141535
TI  - Nuclear aggregation of olfactory receptor genes governs their monogenic
      expression.
AB  - Gene positioning and regulation of nuclear architecture are thought to influence
      gene expression. Here, we show that, in mouse olfactory neurons, silent olfactory
      receptor (OR) genes from different chromosomes converge in a small number of
      heterochromatic foci. These foci are OR exclusive and form in a cell-type
      specific and differentiation-dependent manner. The aggregation of OR genes is
      developmentally synchronous with the downregulation of lamin b receptor (LBR) and
      can be reversed by ectopic expression of LBR in mature olfactory neurons. LBR
      induced reorganization of nuclear architecture and disruption of OR aggregates
      perturbs the singularity of OR transcription and disrupts the targeting
      specificity of the olfactory neurons. Our observations propose spatial
      sequestering of heterochromatinized OR family members as a basis of monogenic and
      monoallelic gene expression.

PMID- 23141536
TI  - Nucleosomal elements that control the topography of the barrier to transcription.
AB  - The nucleosome represents a mechanical barrier to transcription that operates as
      a general regulator of gene expression. We investigate how each nucleosomal
      component-the histone tails, the specific histone-DNA contacts, and the DNA
      sequence-contributes to the strength of the barrier. Removal of the tails favors
      progression of RNA polymerase II into the entry region of the nucleosome by
      locally increasing the wrapping-unwrapping rates of the DNA around histones. In
      contrast, point mutations that affect histone-DNA contacts at the dyad abolish
      the barrier to transcription in the central region by decreasing the local
      wrapping rate. Moreover, we show that the nucleosome amplifies sequence-dependent
      transcriptional pausing, an effect mediated through the structure of the nascent
      RNA. Each of these nucleosomal elements controls transcription elongation by
      affecting distinctly the density and duration of polymerase pauses, thus
      providing multiple and alternative mechanisms for control of gene expression by
      chromatin remodeling and transcription factors.

PMID- 23141537
TI  - Operational plasticity enables hsp104 to disaggregate diverse amyloid and
      nonamyloid clients.
AB  - It is not understood how Hsp104, a hexameric AAA+ ATPase from yeast,
      disaggregates diverse structures, including stress-induced aggregates, prions,
      and alpha-synuclein conformers connected to Parkinson disease. Here, we establish
      that Hsp104 hexamers adapt different mechanisms of intersubunit collaboration to
      disaggregate stress-induced aggregates versus amyloid. To resolve disordered
      aggregates, Hsp104 subunits collaborate noncooperatively via probabilistic
      substrate binding and ATP hydrolysis. To disaggregate amyloid, several subunits
      cooperatively engage substrate and hydrolyze ATP. Importantly, Hsp104 variants
      with impaired intersubunit communication dissolve disordered aggregates, but not
      amyloid. Unexpectedly, prokaryotic ClpB subunits collaborate differently than
      Hsp104 and couple probabilistic substrate binding to cooperative ATP hydrolysis,
      which enhances disordered aggregate dissolution but sensitizes ClpB to inhibition
      and diminishes amyloid disaggregation. Finally, we establish that Hsp104 hexamers
      deploy more subunits to disaggregate Sup35 prion strains with more stable "cross
      beta" cores. Thus, operational plasticity enables Hsp104 to robustly dissolve
      amyloid and nonamyloid clients, which impose distinct mechanical demands.

PMID- 23141538
TI  - Protein folding drives disulfide formation.
AB  - PDI catalyzes the oxidative folding of disulfide-containing proteins. However,
      the sequence of reactions leading to a natively folded and oxidized protein
      remains unknown. Here we demonstrate a technique that enables independent
      measurements of disulfide formation and protein folding. We find that non-native
      disulfides are formed early in the folding pathway and can trigger misfolding. In
      contrast, a PDI domain favors native disulfides by catalyzing oxidation at a late
      stage of folding. We propose a model for cotranslational oxidative folding
      wherein PDI acts as a placeholder that is relieved by the pairing of cysteines
      caused by substrate folding. This general mechanism can explain how PDI catalyzes
      oxidative folding in a variety of structurally unrelated substrates.

PMID- 23141539
TI  - HDAC4 governs a transcriptional program essential for synaptic plasticity and
      memory.
AB  - Neuronal activity influences genes involved in circuit development and
      information processing. However, the molecular basis of this process remains
      poorly understood. We found that HDAC4, a histone deacetylase that shuttles
      between the nucleus and cytoplasm, controls a transcriptional program essential
      for synaptic plasticity and memory. The nuclear import of HDAC4 and its
      association with chromatin is negatively regulated by NMDA receptors. In the
      nucleus, HDAC4 represses genes encoding constituents of central synapses, thereby
      affecting synaptic architecture and strength. Furthermore, we show that a
      truncated form of HDAC4 encoded by an allele associated with mental retardation
      is a gain-of-function nuclear repressor that abolishes transcription and synaptic
      transmission despite the loss of the deacetylase domain. Accordingly, mice
      carrying a mutant that mimics this allele exhibit deficits in neurotransmission,
      spatial learning, and memory. These studies elucidate a mechanism of experience
      dependent plasticity and define the biological role of HDAC4 in the brain.

PMID- 23141541
TI  - The spinocerebellar ataxia-associated gene Tau tubulin kinase 2 controls the
      initiation of ciliogenesis.
AB  - The primary cilium has critical roles in human development and disease, but the
      mechanisms that regulate ciliogenesis are not understood. Here, we show that Tau
      tubulin kinase 2 (TTBK2) is a dedicated regulator of the initiation of
      ciliogenesis in vivo. We identified a null allele of mouse Ttbk2 based on loss of
      Sonic hedgehog activity, a signaling pathway that requires the primary cilium.
      Despite a normal basal body template, Ttbk2 mutants lack cilia. TTBK2 acts at the
      distal end of the basal body, where it promotes the removal of CP110, which caps
      the mother centriole, and promotes recruitment of IFT proteins, which build the
      ciliary axoneme. Dominant truncating mutations in human TTBK2 cause
      spinocerebellar ataxia type 11 (SCA11); these mutant proteins do not promote
      ciliogenesis and inhibit ciliogenesis in wild-type cells. We propose that cell
      cycle regulators target TTBK2 to the basal body, where it modifies specific
      targets to initiate ciliogenesis.

PMID- 23141540
TI  - Senataxin associates with replication forks to protect fork integrity across RNA
      polymerase-II-transcribed genes.
AB  - Transcription hinders replication fork progression and stability. The ATR
      checkpoint and specialized DNA helicases assist DNA synthesis across
      transcription units to protect genome integrity. Combining genomic and genetic
      approaches together with the analysis of replication intermediates, we searched
      for factors coordinating replication with transcription. We show that the
      Sen1/Senataxin DNA/RNA helicase associates with forks, promoting their
      progression across RNA polymerase II (RNAPII)-transcribed genes. sen1 mutants
      accumulate aberrant DNA structures and DNA-RNA hybrids while forks clash head-on
      with RNAPII transcription units. These replication defects correlate with
      hyperrecombination and checkpoint activation in sen1 mutants. The Sen1 function
      at the forks is separable from its role in RNA processing. Our data, besides
      unmasking a key role for Senataxin in coordinating replication with
      transcription, provide a framework for understanding the pathological mechanisms
      caused by Senataxin deficiencies and leading to the severe neurodegenerative
      diseases ataxia with oculomotor apraxia type 2 and amyotrophic lateral sclerosis
      4.

PMID- 23141542
TI  - Fast-forward genetics identifies plant CPL phosphatases as regulators of miRNA
      processing factor HYL1.
AB  - MicroRNAs (miRNAs) are processed from primary transcripts that contain partially
      self-complementary foldbacks. As in animals, the core microprocessor in plants is
      a Dicer protein, DICER-LIKE1 (DCL1). Processing accuracy and strand selection is
      greatly enhanced through the RNA binding protein HYPONASTIC LEAVES 1 (HYL1) and
      the zinc finger protein SERRATE (SE). We have combined a luciferase-based genetic
      screen with whole-genome sequencing for rapid identification of new regulators of
      miRNA biogenesis and action. Among the first six mutants analyzed were three
      alleles of C-TERMINAL DOMAIN PHOSPHATASE-LIKE 1 (CPL1)/FIERY2 (FRY2). In the
      miRNA processing complex, SE functions as a scaffold to mediate CPL1 interaction
      with HYL1, which needs to be dephosphorylated for optimal activity. In the
      absence of CPL1, HYL1 dephosphorylation and hence accurate processing and strand
      selection from miRNA duplexes are compromised. Our findings thus define a new
      regulatory step in plant miRNA biogenesis.

PMID- 23141543
TI  - UAP56 couples piRNA clusters to the perinuclear transposon silencing machinery.
AB  - piRNAs silence transposons during germline development. In Drosophila,
      transcripts from heterochromatic clusters are processed into primary piRNAs in
      the perinuclear nuage. The nuclear DEAD box protein UAP56 has been previously
      implicated in mRNA splicing and export, whereas the DEAD box protein Vasa has an
      established role in piRNA production and localizes to nuage with the piRNA
      binding PIWI proteins Ago3 and Aub. We show that UAP56 colocalizes with the
      cluster-associated HP1 variant Rhino, that nuage granules containing Vasa
      localize directly across the nuclear envelope from cluster foci containing UAP56
      and Rhino, and that cluster transcripts immunoprecipitate with both Vasa and
      UAP56. Significantly, a charge-substitution mutation that alters a conserved
      surface residue in UAP56 disrupts colocalization with Rhino, germline piRNA
      production, transposon silencing, and perinuclear localization of Vasa. We
      therefore propose that UAP56 and Vasa function in a piRNA-processing compartment
      that spans the nuclear envelope.

PMID- 23141544
TI  - Protection from feed-forward amplification in an amplified RNAi mechanism.
AB  - The effectiveness of RNA interference (RNAi) in many organisms is potentiated
      through the signal-amplifying activity of a targeted RNA-directed RNA polymerase
      (RdRP) system that can convert a small population of exogenously-encountered
      dsRNA fragments into an abundant internal pool of small interfering RNA (siRNA).
      As for any biological amplification system, we expect an underlying architecture
      that will limit the ability of a randomly encountered trigger to produce an
      uncontrolled and self-escalating response. Investigating such limits in
      Caenorhabditis elegans, we find that feed-forward amplification is limited by
      biosynthetic and structural distinctions at the RNA level between (1) triggers
      that can produce amplification and (2) siRNA products of the amplification
      reaction. By assuring that initial (primary) siRNAs can act as triggers but not
      templates for activation, and that the resulting (secondary) siRNAs can enforce
      gene silencing on additional targets without unbridled trigger amplification, the
      system achieves substantial but fundamentally limited signal amplification.

PMID- 23141545
TI  - The loop position of shRNAs and pre-miRNAs is critical for the accuracy of dicer
      processing in vivo.
AB  - Short hairpin RNA (shRNA)-induced RNAi is used for biological discovery and
      therapeutics. Dicer, whose normal role is to liberate endogenous miRNAs from
      their precursors, processes shRNAs into different biologically active siRNAs,
      affecting their efficacy and potential for off-targeting. We found that, in
      cells, Dicer induced imprecise cleavage events around the expected sites based on
      the previously described 5'/3' counting rules. These promiscuous noncanonical
      cleavages were abrogated when the cleavage site was positioned 2 nt from a bulge
      or loop. Interestingly, we observed that the ~1/3 of mammalian endogenous pre
      miRNAs that contained such structures were more precisely processed by Dicer.
      Implementing a "loop-counting rule," we designed potent anti-HCV shRNAs with
      substantially reduced off-target effects. Our results suggest that Dicer
      recognizes the loop/bulge structure in addition to the ends of shRNAs/pre-miRNAs
      for accurate processing. This has important implications for both miRNA
      processing and future design of shRNAs for RNAi-based genetic screens and
      therapies.

PMID- 23141547
TI  - Emerging drug therapies for frailty.
AB  - The metaphor of a frail older person as a car running out of petrol seems to have
      resonance in the lay media. Though it may be an over simplistic representation of
      a complex and dynamic process, it does facilitate discussion with patients and
      their relatives about the appropriateness of interventions, such as whether or
      not there is enough fuel (physiological reserves) to get up a really steep hill
      (undergo a coronary bypass graft). It can also be used as a way to emphasise what
      can be done to help. For example, in some longitudinal studies, 5% of older
      patients are less frail after 5 years follow up, suggesting there are things that
      can still be done to "fill up the tank". This review will consider whether drug
      therapies can fulfil this role. Frail older people are often prescribed long
      lists of medications but it is debatable whether current treatments actually
      address the causes or consequences of frailty itself. Here, we explore the
      associations between frailty and co-morbidity and evaluate whether the management
      of chronic disease may impact frailty development or progression. We consider how
      the management of hypertension may have an important role in the prevention of
      frailty, mediated by reduction of cerebrovascular disease, but why aggressive
      management of hypertension may have negative consequences for those who are
      already frail. We also summarise the evidence linking immunosenescence,
      inflammation and endocrine changes to frailty and investigate whether targeted
      drug therapy has the potential to influence frailty pathophysiology.

PMID- 23141546
TI  - SnapShot: cortical development.

PMID- 23141548
TI  - Synthesis, radiolabeling and bioevaluation of a novel arylpiperazine derivative
      containing triazole as a 5-HT1A receptor imaging agents.
AB  - INTRODUCTION: It has been recognized that serotonin plays a main role in various
      pathological conditions such as anxiety, depression, aggressiveness,
      schizophrenia, suicidal behavior, panic and autism. 1-(2-Methoxyphenyl)
      piperazine pharmacophore, a fragment of the true 5-HT(1A) antagonist WAY100635,
      is found in numerous selective 5-HT(1A) imaging agents. In this paper, we have
      reported the synthesis of a novel derivative of 1-(2-methoxyphenyl) piperazine
      that is labeled with (99m)Tc (CO)(3) via click chemistry. METHODS: The bidentate
      alkyne, propargylglycine was reacted with phenyl piperazine triazole derivative
      in the presence of a catalytic amount of Cu (I) to form tridentate ligand. The
      ligand was radiolabeled with the precursor [(99m)Tc] [(H(2)O)(3) (CO)(3)](+) and
      characterized by HPLC. The bioevaluation of radio labeled ligand was carried out
      in rats. RESULTS: Triazole complex was labeled by (99m)Tc-tricarbonyl and its
      radiochemical yield was more than >95% which was determined by HPLC. In vivo
      stability studies in human serum albumin show a 93% ratio of complex after a 24h
      period. The calculated partition coefficient (logP) was 0.34+/-0.02. Receptor
      binding assays indicated about 70% specific binding of radioligand to 5-HT(1A)
      receptors. Biodistribution studies have shown brain hippocampus uptake of 0.40+/
      0.08 %ID/g at 30 min post injection. CONCLUSIONS: Results indicate that this
      (99m)Tc-tricabonyl-arylpiperazine derivative has specific binding to 5-HT(1A)
      receptors and presented suitable characters for its use as a CNS imaging agent.

PMID- 23141549
TI  - Synthesis and biological evaluation of [11C]SB366791: a new PET-radioligand for
      in vivo imaging of the TRPV1 receptor.
AB  - INTRODUCTION: The transient receptor potential vanilloid subfamily member 1
      (TRPV1) receptor, a non-selective cation channel, is known for its key role in
      pain nociception and neurogenic inflammation. TRPV1 expression has been
      demonstrated in diverse tissues and an essential role for TRPV1 in various
      disorders has been suggested. A TRPV1-specific PET-radioligand can serve as a
      useful tool for further in vivo research in animals and directly in humans. In
      this study, we report the synthesis and biological evaluation of a carbon-11
      labelled analogue of N-(3-methoxyphenyl)-4-chlorocinnamide (SB366791) which was
      reported as a specific high-affinity antagonist for TRPV1. METHODS: The new
      tracer was evaluated with respect to log D and biodistribution in control,
      pretreated and TRPV1-/- mice. The percentage of radiometabolites of [11C]SB366791
      was determined in mouse plasma and brain. RESULTS: [11C] SB366791 was obtained in
      good yield (69%+/-11%; isolated amounts 3034-5032MBq) and high specific activity
      (390+/-215 GBq/MUmol). The tracer was efficiently cleared from blood and all
      major organs via hepatobiliary and renal pathways. Initial brain uptake was high
      (1.6% ID) and wash-out from brain was rapid. The retention of [11C] SB366791 in
      the trigeminal nerve of control mice was prominent. The in vitro binding affinity
      of SB366791 was determined to be 280+/-56 nM and 780+/-140 nM for human and rat
      TRPV1, respectively. CONCLUSIONS: [11C] SB366791 has favourable biodistribution
      characteristics in mice. However the obtained low binding affinity for TRPV1 may
      not be sufficient to use the current compound as PET tracer.

PMID- 23141550
TI  - Radiosynthesis, biodistribution and imaging of [11C]YM155, a novel survivin
      suppressant, in a human prostate tumor-xenograft mouse model.
AB  - INTRODUCTION: Sepantronium bromide (YM155) is an antitumor drug in development
      and is a first-in-class chemical entity, which is a survivin suppressant. We
      developed a radiosynthesis of [(11)C]YM155 to non-invasively evaluate its tissue
      and tumor distribution in mice bearing human prostate tumor xenografts. METHODS:
      Methods utilizing [(11)C]acetyl chloride and [(11)C]methyl triflate, both
      accessible with automated radiosynthesis boxes, were evaluated. The O-methylation
      of ethanolamine-alkolate with [(11)C]methyl triflate proved to be the key
      development toward a rapid and efficient process. The whole-body distribution of
      [(11)C]YM155 in PC-3 xenografted mice was examined using a planar positron
      imaging system (PPIS). RESULTS: Sufficient quantities of radiopharmaceutical
      grade [(11)C]YM155 were produced for our PET imaging and distribution studies.
      The decay corrected (EOB) radiochemical yield was 16-22%, within a synthesis time
      of 47 min. The radiochemical purity was higher than 99%, and the specific
      activity was 29-60 GBq/MUmol (EOS). High uptake levels of radioactivity (%ID/g,
      mean+/-SE) were observed in tumor (0.0613+/-0.0056), kidneys (0.0513+/-0.0092),
      liver (0.0368+/-0.0043) and cecum (0.0623+/-0.0070). The highest tumor uptake was
      observed at an early time point (from 10 min after) following injection. Tumor-to
      blood and tumor-to-muscle uptake ratios of [(11)C]YM155, at 40 min after
      injection, were 26.5 (+/-2.9) and 25.6 (+/-3.6), respectively. CONCLUSION: A
      rapid method for producing a radiopharmaceutical grade [(11)C]YM155 was
      developed. An in vivo distribution study using PPIS showed high uptake of
      [(11)C]YM155 in tumor tissue. Our methodology may facilitate the evaluation and
      prediction of response to YM155, when given as an anti-cancer agent.

PMID- 23141551
TI  - Longitudinal observation of [11C]4DST uptake in turpentine-induced inflammatory
      tissue.
AB  - INTRODUCTION: Longitudinal changes of 4'-[methyl-(11)C]thiothymidine
      ([(11)C]4DST) uptake were evaluated in turpentine-induced inflammation. METHODS:
      Turpentine (0.1 ml) was injected intramuscularly into the right hind leg of male
      Wistar rats. Longitudinal [(11)C]4DST uptake was evaluated by the tissue
      dissection method at 1, 2, 4, 7, and 14 days after turpentine injection (n=5).
      The tumor selectivity index was calculated using the previously published
      biodistribution data in C6 glioma-bearing rats. Dynamic PET scan was performed on
      day 4 when maximum [(11)C]4DST uptake was observed during the longitudinal study.
      Histopathological analysis and Ki-67 immunostaining were also performed. RESULTS:
      The uptake of [(11)C]4DST in inflammatory tissue was significantly increased on
      days 2-4 after turpentine injection, and then decreased. On day 14, tracer uptake
      returned to the day 1 level. The maximum SUV of inflamed muscle was 0.6 and was 3
      times higher than that of the contralateral healthy muscle on days 2-4 after
      turpentine injection. However, tumor selectivity index remains very high (>10)
      because of the low inflammation uptake. A dynamic PET scan showed that the
      radioactivity in inflammatory tissues peaked at 5 min after [(11)C]4DST
      injection, and then washed out until 20 min. At intervals >20 min, radioactivity
      levels were constant and double that of healthy muscle. The changes in Ki-67
      index were paralleled with those of [(11)C]4DST uptake, indicating cell
      proliferation-dependent uptake of [(11)C]4DST in inflammatory tissues.
      CONCLUSION: In our animal model, low but significant levels of [(11)C]4DST uptake
      were observed in subacute inflammation.

PMID- 23141553
TI  - Peri-operative cardiac arrest with ST elevation secondary to gelofusin
      anaphylaxis - Kounis syndrome in the anaesthetic room.

PMID- 23141552
TI  - Nicotinic alpha4beta2 receptor imaging agents. Part IV. Synthesis and biological
      evaluation of 3-(2-(S)-3,4-dehydropyrrolinyl methoxy)-5-(3'-18F
      fluoropropyl)pyridine (18F-Nifrolene) using PET.
AB  - Imaging agents for nicotinic alpha4beta2 receptors in the brain have been under
      way for studying various CNS disorders. Previous studies from our laboratories
      have reported the successful development of agonist, 18F-nifene. In attempts to
      develop potential antagonists, 18F-nifrolidine and 18F-nifzetidine were
      previously reported. Further optimization of these fluoropropyl derivatives has
      now been carried out resulting in 3-(2-(S)-3,4-dehydropyrrolinylmethoxy)-5-(3'
      Fluoropropyl)pyridine (nifrolene) as a new high affinity agent for nicotinic
      alpha4beta2 receptors. Nifrolene in rat brain homogenate assays--labeled with 3H
      cytisine--exhibited a binding affinity of 0.36 nM. The fluorine-18 analog, 18F
      nifrolene, was synthesized in approximately 10%-20% yield and specific activity
      was estimated to be >2000 Ci/mmol. Rat brain slices indicated selective binding
      to anterior thalamic nuclei, thalamus, subiculum, striata, cortex and other
      regions consistent with alpha4beta2 receptor distribution. This selective binding
      was displaced >90% by 300 MUM nicotine. Thalamus to cerebellum ratio (>10) was
      the highest for 18F-nifrolene with several other regions showing selective
      binding. In vivo rat PET studies exhibited rapid uptake of 18F-nifrolene in the
      brain with specific retention in the thalamus and other brain regions while
      clearing out from the cerebellum. Thalamus to cerebellum ratio value in the rat
      was >4. Administration of nicotine caused a rapid decline in the thalamic 18F
      nifrolene suggesting reversible binding to nicotinic receptors. PET imaging
      studies of 18F-nifrolene in anesthetized rhesus monkey revealed highest binding
      in the thalamus followed by regions of the lateral cingulated and temporal
      cortex. Cerebellum showed the least binding. Thalamus to cerebellum ratio in the
      monkey brain was >3 at 120 min. These ratios of 18F-nifrolene are higher than
      measured for 18F-nifrolidine and 18F-nifzetidine. 18F-Nifrolene thus shows
      promise as a new PET imaging agent for alpha4beta2 nAChR.

PMID- 23141554
TI  - [Current status of fibreoptic bronchoscopy in intensive care medicine].
AB  - Flexible bronchoscopy (FB) has been of great help in the management of critically
      ill patients. Its safety and usefulness in the hands of experienced
      professionals, with the required measures of caution, has resulted in the
      increasingly widespread use of the technique even in unstable critical patients
      subjected to mechanical ventilation and with high oxygen demands. The Spanish
      Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC),
      through its Acute Respiratory Failure (GT-IRA) and Infectious Diseases (GT-EI)
      Work Groups, aims to promote knowledge and standards of quality in the use of FB
      among all specialists in Intensive Care Medicine. Through an expert committee,
      the SEMICYUC has established the objective of accrediting such training, with the
      preparation of a curriculum and definition of those Units qualified for providing
      training in the different techniques and levels. The accreditation process seeks
      to stimulate good learning practice and quality in training. Both specialists in
      Intensive Care Medicine and other specialists, and the patients, will benefit
      from the commitment and control afforded by such accreditation, and from the
      learning and training which the mentioned process entails.

PMID- 23141555
TI  - Gender differences in approaches to self-management of poor sleep in later life.
AB  - In this paper we seek to understand the influence of gender on the different
      approaches to managing poor sleep by older men and women through the conceptual
      framework of existing theoretical debates on medicalization, healthicization and
      'personalization'. In-depth interviews undertaken between January and July 2008
      with 62 people aged 65-95 who were experiencing poor sleep, revealed that the
      majority of older men and women resisted the medicalization of poor sleep, as
      they perceived sleep problems in later life were an inevitable consequence of
      ageing. However, older men and women engaged differently with the healthicization
      of poor sleep, with women far more likely than men to explore a range of
      alternative sleep remedies, such as herbal supplements, and were also much more
      likely than men to engage in behavioural practices to promote good sleep, and to
      avoid practices which prevented sleep. Women situated 'sleep' alongside more
      abstract discussions of 'diet' and health behaviours and drew on the discourses
      of the media, friends, family and their own experiences to create 'personalized'
      strategies, drawn from a paradigm of healthicization. Men, however, solely relied
      on the 'body' to indicate when sleep was needed and gauged their sleep needs
      largely by how they felt, and were able to function the following day.

PMID- 23141556
TI  - Organochlorine pesticide residues in maternal blood, cord blood, placenta, and
      breastmilk and their relation to birth size.
AB  - There is a growing concern that persistent organic pollutants like organochlorine
      pesticides (OCPs) can impair fetal growth and affect birth size. However,
      currently available epidemiological evidence is inconclusive. In this case
      control study, we examined the association between exposure to
      hexachlorocyclohexane (HCH) and its isomers (alpha-HCH, beta-HCH and gamma-HCH),
      dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethylene (DDE)
      and birth size. We recruited 60 infant-mother pairs, comprising of 30 term, small
      for gestational age babies with their mothers (Case group), and another 30 term,
      appropriate for gestational age babies with their mothers (Control group). This
      study was conducted in a tertiary hospital in Delhi, India, between March, 2009
      and February 2010. Organochlorine pesticides were estimated in maternal blood,
      cord blood, placenta and breastmilk samples, using gas-liquid chromatography.
      Transplacental and transmammary transfer of OCPs was assessed by correlating the
      maternal blood OCP levels with those in cord blood and breastmilk by simple
      linear regression. The birthweight, crown heel length, head circumference, mid
      arm circumference and ponderal index of the neonates was correlated with OCP
      levels in the maternal blood, cord blood, placenta and breastmilk. The OCP
      estimates were compared between samples of the case and control group. There was
      a significant (P<0.001) transplacental transfer of all OCPs, however the
      transmammary transfer was insignificant for most OCPs except alpha-HCH. The OCP
      levels in the case group were higher than the control group; these were
      significantly more for t-HCH in cord blood and breastmilk; beta-HCH in maternal
      blood, cord blood and breastmilk; DDE in placenta and DDT in breastmilk. There
      was a significant negative correlation between birthweight and t-HCH levels in
      maternal blood (P=0.022), cord blood (P<0.001), placenta (P=0.008) and breastmilk
      (P=0.005); beta-HCH in cord blood (P<0.001) and placenta (P=0.020); gamma-HCH in
      placenta (P=0.045); and DDT (P=0.009). Length at birth had a significant negative
      correlation with t-HCH in cord blood (P=0.014) and breastmilk (P<0.001); beta-HCH
      in cord blood (P=0.016) and breastmilk (P=0.012); DDE in placenta (P=0.016); and
      DDT in breastmilk (P=0.006). Similarly, OCP levels were also found to be
      negatively correlated with head circumference, ponderal index and chest
      circumference in neonates. We conclude that prenatal exposure to some OCPs could
      impair the anthropometric development of the fetus, reducing the birthweight,
      length, head circumference, chest circumference and ponderal index.

PMID- 23141557
TI  - Mercury bioaccumulation and decontamination kinetics in the edible cockle
      Cerastoderma edule.
AB  - Mercury bioaccumulation and decontamination kinetics in the edible cockle
      Cerastoderma edule were studied through a mesocosms experiment after a medium
      term exposure to the metal. The results revealed that the bivalve presented
      distinct bioaccumulation kinetics according to the different tissues. While the
      gills showed a linear accumulation pattern, the digestive gland and the entire
      organism presented a saturation model, with higher accumulation during the first
      7d of exposure and lower during the rest of the time. In addition, the
      bioaccumulation rate was not proportional to the Hg concentration, since the
      organisms under lower contamination presented higher bioconcentration factors
      than the ones under higher contamination. Gills were the tissues with higher
      mercury accumulation capability. Concerning the decontamination phase, C. edule
      lost approximately 80% of the mercury after 24h exposure in clean seawater.
      Nevertheless, never reached the original condition, showing in the final (20 d
      detox), Hg levels (>0.5 ppm) higher than those allowed by the legislation
      regulating human food consumption. This represents a matter of concern for Human
      health.

PMID- 23141558
TI  - Influence of age, season, body condition and geographical area on concentrations
      of chlorinated and brominated contaminants in wild mink (Neovison vison) in
      Sweden.
AB  - The wild mink has gained acceptance as a sentinel species in environmental
      monitoring. However, only limited data are available in the literature on factors
      driving variability in concentrations of organic pollutants in this species. This
      study characterizes the differences in contaminant concentrations in subcutaneous
      fat of male mink from four different areas in Sweden and demonstrates how age,
      season and body condition influence concentrations of polychlorinated biphenyl
      (PCB) congeners, polybrominated diphenyl ether (PBDE) congeners (including
      methoxylated forms, MeO-PBDEs), as well as the pesticides
      dichlorodiphenyldichloroethylene (DDE), chlordane and hexachlorobenzene (HCB).
      The data were statistically treated using multiple regression and principal
      component analysis. The ?PCB concentration and concentrations of PCB congeners
      138, 156, 157, 180, 170/190, 189, 194, 206, 209 as well as PBDE 153/154 varied
      with age. Season had an influence on ?PCB, PBDE 47 and PBDE 153/154
      concentrations, as well as concentrations of most PCB congeners, with the
      exception of PCB 101, 110, 141 and 182/187. Lean mink had higher concentrations
      of most PCBs and PBDEs than mink with larger fat depots. The analyzed pesticides
      (DDE, oxychlordane, HCB) showed no systematic variation with season, age or body
      condition. The concentrations of MeO-PBDEs were generally low and 6MeO-PBDE 47
      was the most commonly detected MeO-PBDE in mink from marine, brackish and
      freshwater areas. The results indicate that age, season and body condition are
      factors that may influence the concentrations of PCBs and PBDEs, and it is thus
      recommended to take these factors into account when analyzing mink exposure data.

PMID- 23141559
TI  - Limb/trunk lean mass ratio as a risk factor for mortality in peritoneal dialysis
      patients.
AB  - BACKGROUND: This study was performed to determine the clinical relevance of
      limb/trunk lean mass ratio (LTLM) in continuous ambulatory peritoneal dialysis
      (CAPD) patients. METHODS: This retrospective cohort study included 534 CAPD
      patients. Body compositions were measured using a dual-energy X-ray
      absorptiometry apparatus. RESULTS: In males, the sensitivity and specificity for
      the diagnosis of sarcopenia were 70.3% and 85.9%, respectively. Respective values
      in females were 62.3% and 83.8%. The initial low LTLM tertile was associated with
      mortality in male CAPD patients and in female CAPD patients. Among patients who
      maintained CAPD for a year, the maintenance of low LTLM tertile was associated
      with mortality. CONCLUSIONS: LTLM is associated with other lean mass indices,
      nutritional status, and mortality in CAPD patients. Therefore, LTLM is a novel
      marker that is useful for the prediction of the nutritional status and mortality
      in patients with CAPD.

PMID- 23141560
TI  - Moving the issue of renal dietitian staffing forward: an international
      perspective.

PMID- 23141561
TI  - Implications of ECASS III error on emergency department treatment of ischemic
      stroke.

PMID- 23141562
TI  - Thrombocytopenia after tetanus prophylaxis with tetanus-diphtheria (Td) vaccine.

PMID- 23141563
TI  - Successful combined use of videolaryngoscopy and pediatric stylet in an adult
      case of acute epiglottitis.

PMID- 23141564
TI  - [Management of caustic esophagitis in children].
AB  - In children, caustic ingestion is due to accidents at home and inadequate storage
      of caustic agents. In emergency, it is useful to remove the soiled clothes, rinse
      the affected area, and prevent vomiting and feeding. Caustic ingestion (pH<2
      or>12) induces burns of the upper gastrointestinal tract requiring esophagogastro
      duodenoscopy between H12 and H24. Strong alkalis cause necrosis with liquefaction
      of the esophagus, penetrating deeply with a high-risk of perforation. Management
      of these children requires a specialized care center with an intensive care unit,
      endoscopic equipment, and a surgical team. Esophageal stricture is the main
      complication; no prophylactic treatment (steroids) is effective. Strictures occur
      after the 3rd week, and barium swallow should be performed by the end of the 1st
      month. Stricture are often multiple, long, and tortuous; endoscopic dilatation is
      difficult with a high-rate of perforation and a low-rate of success. In situ
      application of mitomycin C or injection of triamcinolone could reduce the
      recurrence rate of stricture. In recalcitrant or recurrent strictures, it is
      recommended to perform an esophageal replacement using a colonic interposition or
      a gastric tube. Endoscopy should also be performed 15-20years after caustic
      ingestion to screen for early neoplastic lesions. Prevention is very important
      for avoiding caustic ingestions. Information and education should be given
      specifically to the parents of toddlers; caustic products should be stored out of
      reach of children and they should not be kept with food.

PMID- 23141565
TI  - [Chest radiographs in infants hospitalized for acute bronchiolitis: real
      information or just irradiation?].
AB  - OBJECTIVE: To describe the chest radiographs of infants hospitalized for acute
      bronchiolitis and to assess whether patient management changed after radiography.
      STUDY DESIGN: All infants hospitalized in our pediatric unit with a first episode
      of acute bronchiolitis from October 2010 to March 2012 were included in the
      study. Infants with chronic disease or transferred from a pediatric intensive
      care unit were excluded. The following data were collected: sex, age, neonatal
      history, atopy, tobacco exposure, admission criteria, treatment, laboratory
      parameters, ultrasonography and its outcome, results of chest radiography on
      admittance, the reason for a second chest radiograph, change in management as a
      result of the radiograph. RESULTS: The study comprised 232 infants (median age
      2.2 months, boys 56%, positive respiratory syncytial virus 73.4%). Among them,
      227 children had a routine chest radiograph revealing distension and/or bronchial
      wall thickening (n=141, 62.4%), focal opacity (19.9%), or atelectasis (17.7%).
      This radiograph led to the prescription of antibiotics in six patients (2.6%) and
      allowed the diagnosis of vascular abnormality to be made in one case (0.4%).
      Thirty-five patients (15.4%) had a second chest radiograph during their
      hospitalization owing to oxygen dependency (n=21), respiratory distress (n=11),
      persistent fever (n=2), or no reason specified (n=1). Pneumonia (n=7) and/or
      atelectasis (n=15) were then found in 62.9%. Patient management (antibiotics,
      postural maneuvers) was modified in six patients (17.1%). CONCLUSIONS: Routine
      chest radiographs contribute only partially to the treatment of infants
      hospitalized for acute bronchiolitis. However, radiography is useful when the
      hospitalized child does not improve at the expected rate or if the disease is
      severe. The indication of chest radiography in infants hospitalized for acute
      bronchiolitis should be discussed on a case by a case basis.

PMID- 23141566
TI  - Human leukocyte antigen-associated drug hypersensitivity.
AB  - A growing number of associations between adverse drug reactions and alleles of
      the human leukocyte antigen (HLA) genes are now known. Although several models
      have been proposed to explain these associations, an underlying molecular basis
      has only recently been described. The associations between HLA-B*57:01 and
      abacavir hypersensitivity syndrome, and HLA-B*15:02 and carbamazepine-induced
      bullous skin disease have provided new insights into the mechanism associated
      with hypersensitivity reactions to these drugs. Here we discuss recent evidence
      that small molecules can interact with specific HLA to distort self-peptide
      presentation leading to autoimmune-like drug hypersensitivities that potentially
      provide clues to the mechanisms underlying other immunopathologies.

PMID- 23141567
TI  - Increasing challenge of primary and secondary prevention of gestational diabetes
      mellitus.

PMID- 23141568
TI  - [Esotropia and hyperopia corrected].
AB  - The subgroups of esotropia exist. The full optical correction of the
      hypermetropic refractive error is theoretically conclusive. The full correction
      further defined the diagnosis of three forms of esotropia. The earlier viewpoint
      that the full optical correction of the hypermetropia will decrease the
      accommodative normal demand or the accommodation is inactive and an exotropia
      will increase. After full correction of the hypermetropia the patients often
      complain about blurring of vision. Moreover, some doctors still have a confused
      ideas about full correction of the hyperopia. The final outcome that of most of
      patients with under-corrected hypermetropia, three commonly forms of esotropia
      (Accommodative esotropia, partially accommodative esotropia and nonaccommodative
      esotropia) will not be clearly differentiated as each requires different clinical
      management.

PMID- 23141569
TI  - [Research on whether atropine can be substituted by the powerful cycloplegic
      cyclopentolate].
AB  - For a long time, atropine eye ointment has been widely used as the cycloplegic
      for children's optometry in China, while internationally, cyclopentolate gutta is
      widely used as the first choice for cycloplegic. In recent years, 1%
      cyclopentolate hydrochloride ocular humor has been introduced to our country.
      This effective and powerful cycloplegic has already been paid close attention to
      by domestic pedo-ophthalmologists. According to a serious of studies both home
      and abroad on the therapeutic effects of the own control drugs, the cycloplegia
      effect of cyclopentolate is close to the atropine. Cyclopentolate can be widely
      used for the cycloplegia before optometry for the Chinese children. However, the
      effect of cyclopentolate is still not as good as atropine. So, for the children
      with farsightedness within 7 years old, all esotropia children, Am children, and
      children who suffer from decreased vision acuteness and needs to be excluded from
      accommodative myopia, atropine eye ointment should be routinely used for
      cycloplegia before optometry. In this article, we also discuss the medication
      dosage, medication method, possible drug adverse reactions of cyclopentolate
      humor ocular and the coping measures at the same time.

PMID- 23141570
TI  - [Recession of both horizontal rectus muscles in Duane Retraction Syndrome with
      significant globe retraction].
AB  - OBJECTIVE: To evaluate the effect of Recession of both horizontal rectus muscles
      in Duane Retraction Syndrome with significant globe retraction. METHODS: Sixteen
      cases with DRS were summarized retrospectively. All patients had undergone
      surgery with recession of both horizontal rectus muscles. All clinical records,
      including sex, age, types of DRS, clinical features, surgical methods and
      clinical outcomes were analyzed. All patients were followed up for 3 months to 1
      year. RESULTS: Fifteen cases had only monocular involvement while one had both
      eyes. The number of type I DRS was 3 cases, 1 case was esotropia while others
      were orthotropic in primary position. Type III DRS was observed 13 cases.
      Esotropia was seen in 6 cases (7 eyes), exotropia of 1 cases and orthotropic in
      primary position of 6 cases. 10 cases exhibited marked face turn. An upshoot or
      downshoot and variable severity of retraction of globe were found in all patients
      on attempt adduction of the affected eye. All patients had undergone surgery with
      recession of both horizontal rectus muscles. The medical rectus muscles were
      recessed from 5 mm to 7 mm and lateral rectus muscles 3 mm to 9 mm
      simultaneously, which was based on the amount of primary position deviation.
      Among these 2 cases were combined with Y-splitting of lateral rectus muscle.
      After surgery, all patients were orthotropic in primary position. Their symptom
      of unacceptable abnormal head position, significant globe retraction, noticeable
      narrowing of the palpebral fissure and significant upshoot or downshoot were
      ameliorated or disappeared. Especially the recession of lateral rectus muscle in
      addition to Y-splitting combining with the simultaneous medial rectus recession
      resulted in further amelioration of globe retraction in addition to upshoot and
      downshoot. CONCLUSION: Recession of both horizontal rectus muscles is effective
      in the treatment of significant globe retraction in Duane syndrome. Type III DRS
      with significant globe retraction but has no marked deviation and face turn can
      adopt this method to ameliorate their aspect. The method of lateral rectus muscle
      in addition to Y-splitting plays an important role in the treatment of upshoot
      and downshoot.

PMID- 23141571
TI  - [Palisade endings of extraocular muscles in eyes with congenital nystagmus].
AB  - OBJECTIVE: To evaluate the morphology, distribution and function of palisade
      endings (PE) in human extraocular muscles (EOM), and observe the alterations in
      eyes with congenital nystagmus (CN). The etiology and pathogenesis of CN were
      also investigated. METHODS: It was a experimental study. The distal myotendinous
      junctions of the EOM were obtained during operation for CN (CN group) and
      concomitant strabismus (control group). The samples from patients with similar
      age and same extraction sites in the two groups were compared. The muscles cut
      during operation were immediately put into 4% glutaraldehyde fixative solution.
      And 1-2 transverse bands of tissue were cut every 1 mm from tendon insertion for
      specimens processing. The ultrastructure of EOM and PE in the two groups was
      observed by transmission electron microscopy. The distal parts of EOM cut during
      operation were put into 4% paraformaldehyde promptly. Myotendinous junction
      region whole mounts were labeled with antibodies against choline
      acetyltransferase (ChAT). Muscle fibers were counterstained with phalloidin. And
      longitudinal and transverse cryostat serial sections were cut at 25 um and
      analyzed by confocal laser scanning microscopy. The ChAT expression, morphology
      and distribution of PE were observed. The same fragment of myotendinous junction
      in the two groups was selected. After the total protein was extracted, ChAT was
      detected by western blot. The expression level of ChAT was analyzed. RESULTS:
      Compared with the controls, the ultrastructure in the CN group had considerable
      variations. The axon of PE was swelled and deformed partly. The electron density
      was increased and presented as addicted to osmic acid. In the muscle cells,
      mitochondria was swelled, and sarcoplasmic reticulum was dilated. All PE
      exhibited ChAT immunoreactivity in human EOM. In the longitudinal section, nerve
      fibers extended from the muscle into the tendon, looped back and divided into
      several terminal arborizations (palisade endings) around the muscle fiber tip.
      The PE of medial rectus were richest at the location 3 - 4 mm from tendon
      insertion. In the cross section, the amount of PE in the CN group was higher than
      the control group (t = -5.613, P < 0.05). The expression level of ChAT in the CN
      group was higher than the control group (t = -3.730, P < 0.05). CONCLUSIONS:
      Palisade endings in myotendinous junction of human EOM are cholinergic nerves,
      which might innervate the contraction of EOM. Significant changes of palisade
      endings in the EOM of the CN subjects may affect eye movement.

PMID- 23141572
TI  - [Comparison between photographic analysis and orthopedic goniometer of
      measurement of compensatory head posture].
AB  - OBJECTIVE: To evaluate the application of relative reference point photographic
      analysis method and goniometer method for head posture measurement, and compare
      the characteristics of the two methods. METHODS: Thirty patients from March 2011
      to April 2011 and August to September with AHP in our hospital were recruited.
      The AHP were measured by photographic analysis and goniometer method
      respectively. The data were analyzed by SPSS software. RESULTS: The mean AHP was
      15.62 degrees  +/- 7.48 degrees  by photographic analysis measurement, 15.50
      degrees  +/- 6.99 degrees  by goniometer measurement. The Pearson's correlation
      coefficient (r = 0.955, P < 0.001, t = 0.286, P = 0.777). CONCLUSIONS: Relative
      reference point photographic analysis is a simple and effective way to measure
      AHP. The results measured by the two methods are highly consistent.

PMID- 23141573
TI  - [Study on the changes of fibronectin in the resected medial rectus of patients
      with concomitant exotropia].
AB  - OBJECTIVE: To study the changes of fibronectin in the resected medial rectus
      muscles in patients with concomitant exotropia and to have a better understanding
      about the pathomorphological changes of extraocular muscles in the genesis and
      development of concomitant exotropia. METHODS: Thirty-five concomitant exotropic
      patients were chosen as exotropic group and 20 normals were selected as control
      group. In the exotropic group, the age range 2 to 46 years old (mean, 20.9 ys),
      deviation range -45(Delta) to -90(Delta) (mean, -67.5(Delta)), 19 males, 16
      females, and 8 cases have the family history. Exotropic patients were divided
      into intermittent exotropic group 16 cases and constant exotropic group 19 cases.
      In the control group, the age range 15 - 28 years old (mean, 18.8 years), 12
      males and 8 females. All the resected tissues of the medial rectus muscles were
      obtained from patients with concomitant exotropia during resection surgery and
      cornea donators. Fibronectin was measured its mean average optical by Sp method
      of immunohistochemistry using image analyzer. The amounts of fibronectin in the
      resected muscle of patients were compared with normals, as well as correlated
      clinical data of patients such as different types of exotropia, age, degree of
      deviation, gender and positive family history. RESULTS: The amounts of
      fibronectin in the resected medial rectus muscle of patients with constant
      exotropia (0.4729 +/- 0.0872) were significantly lower than those of normals
      (0.5914 +/- 0.0547) and intermittent exotropic group (0.5821 +/- 0.0792)
      respectively (q = 7.0314, 6.1177, P < 0.01), while patients with intermittent
      exotropia did not show significantly lower amounts of fibronectin than those with
      normals (q = 0.5271, P > 0.05). Neither gender nor positive family was correlated
      with the amounts of fibronectin (t = 1.1317, 1.6327, P > 0.05) and the amounts of
      fibronectin had no correlation with age and degree of deviation. CONCLUSION: The
      amounts of fibronectin were correlated with the course of development of
      concomitant exotropia. Some of these changes may play a role in the pathogenesis
      of exotropia from intermittence to constancy, which indicates a further clue to
      the nature of this disease.

PMID- 23141574
TI  - [The variation characters of EPSC-IPSC in rat visual cortex II/III pyramidal
      neurons during critical period of visual development].
AB  - OBJECTIVE: To observe the characters of EPSC-IPSC induced by paired-pulse
      stimulation of rat visual cortex layer II/III pyramidal neurons during critical
      period of visual development, and discuss their relationships, to discuss the
      role of short-term synaptic plasticity in the critical period of visual
      development of rats. METHODS: Thirty Wistar rats were used, they were divided
      into P10-P12, P14-P16, P21-P23, P28-P30, P35-P37 five groups, n = 6. Whole-cell
      voltage clamp recording was performed, the membrane potential was clamped on -50
      mV, 0 mV respectively to separate EPSC and IPSC. We set the PPR as the
      observation indicator, analyzed the developmental features of EPSC and IPSC
      induced by paired-pulse stimulation of different groups. RESULTS: The PPR of
      layer II/III pyramidal neurons in group P10-P12, P14-P16, P21-P23, P28-P30, P35
      P37 was 0.43 +/- 0.08, 0.07 +/- 0.08, 0.10 +/- 0.10, 0.20 +/- 0.07, 0.22 +/- 0.12
      respectively. The PPR of group P14-P16 decreased, the difference was
      statistically significant compared with the group before eyes open (t = -3.13, P
      = 0.04). The PPR of corresponding groups was 0.6036 +/- 0.3021, 0.2830 +/-
      0.0504, 0.0287 +/- 0.0907, -0.0449 +/- 0.1443, -0.3089 +/- 0.05553 respectively
      (F = 5.0799, P = 0.0037), the PPR of IPSC gradually reduced with age, and turned
      negative from the P28-P30 group, changed from PPF to PPD. CONCLUSIONS: The PPR of
      EPSC response to visual stimuli rapidly, but did not change significantly in the
      critical period of visual development (P19-P32). The short-term depression of
      IPSC increased gradually from the eyes open to the end of the critical period of
      visual development, which may play a more important role in the process of layer
      II/III pyramidal neurons maturation and the critical period of visual development
      ending.

PMID- 23141575
TI  - [Clinical research of the phakic foldable angle-supported intraocular lens for
      the correction of high myopia].
AB  - OBJECTIVE: To assess the safety, efficacy, predictability and stability of the
      phakic foldable angle-supported intraocular lens (IOL) (CACHET IOL, Alcon Inc.,
      USA.) for correction of high-to-extremely high myopia in adults. METHODS: In this
      prospective study, 29 eyes of 15 patients were implanted with CACHET phakic angle
      supported IOL and followed for 1 year postoperatively. Preoperative manifest
      refractive sphere was -12.08 +/- 2.44 diopters (D). Visual acuity(uncorrected
      visual acuity, UCVA; best spectacle-corrected visual acuity, BSCVA),
      predictability and stability of manifest refraction spherical equivalent (MRSE),
      adverse events, and endothelial cell density were analyzed primarily during 1
      year of follow-up. RESULTS: After 1 year of follow-up, a BSCVA of 0.6 or better
      was achieved by 100% of eyes; 9.7% (26/29) had a BSCVA of 1.0 or better; no eyes
      lost >= 1 line BSCVA, 62.1%(18/29) had no change in lines of BSCVA, 31.0% (9/29)
      gained 1 line of BSCVA, 3.4% (1/29) gained 2 line of BSCVA, and 3.4% (1/29)
      gained more than 2 line of BSCVA; the safety index was 1.13 (1.08/0.96); UCVA of
      1.0 or better was achieved by 58.6% (17/29), 100% had an UCVA of 0.5 or better,
      86.2% (25/29) of eyes achieved a UCVA of 0.8 or better, and 93.1% (27/29) of eyes
      achieved a UCVA of 0.6 or better; the efficacy index was 1.03(0.99/0.96). The
      overall mean percentage change in endothelial cell density 1 year after surgery
      was -0.23% +/- 4.80%. Five eyes (17.2%) had increased intraocular pressure (IOP)
      on the day of surgery. No pupil ovalization, pupillary block, or retinal
      detachment events were observed. Glare (6.9%, 2/29) and halo (13.8%, 4/29) mainly
      appeared in the first month after surgery, and had no influence on driving in
      night. CONCLUSIONS: After 1 year of follow-up, the implantation of phakic
      foldable angle-supported IOL was proved to be safe, effective and predictable
      with minimal complications in patients with high myopia. Due to the limitation of
      visiting time, long-term of clinical investigation is necessary to verify the
      safety and efficacy of this IOL.

PMID- 23141576
TI  - [Investigation of ophthalmic resources in Xinjiang Uyghur Autonomous Region in
      China].
AB  - OBJECTIVES: To explore ophthalmic resources and existing problems in Xinjiang
      Uyghur Autonomous Region, and to provide reasonable developing configuration for
      the future. METHODS: It was a population-based cross-section study. By using
      questionnaire to collect data from all eye units (national and private) which
      were registered in Xinjiang area. Investigation included: (1) ophthalmic medical
      unit of name, structure type, departments constitute; (2) the ophthalmic medical
      work; (3) the number of ophthalmology health technicians and distribution; (4)
      ophthalmic devices usage; (5) carry out the problems and difficulties encountered
      in ophthalmic work. Descriptive statistic method was used to analyze the
      structure of ophthalmic material, the availability of resource, the medical
      institution of different regions and types. RESULTS: One hundred and thirty
      questionnaire were filled out and 110 questionnaire were recovery. There were 107
      eye units, 1709 beds for ophthalmic, 1672 employees, including 525 doctors, the
      ratio of doctors and nurses was 1.0:1.3. And the ophthalmic resources mainly
      distributed in northern Tianshan, very few in the eastern area in Xinjiang;
      ophthalmic units were denser in general hospitals which were above the county
      level. There were 43 580 ophthalmic surgeries in all, the main eye operation
      carried out was cataract surgery, including 20 303 (counted 46.59%) cataract
      operation. CONCLUSIONS: The ophthalmic units distribution is unbalanced, which is
      short of ophthalmologists. It provides base for government to arrange ophthalmic
      resources reasonably, to enhance the research motivation and to cultivate more
      professors, and to increase the number of ophthalmic specialists in the general
      hospitals, and eventually to maximize the benefit of ophthalmic service in
      Xinjiang.

PMID- 23141577
TI  - [Analysis of gene mutation in a Chinese family with Norrie disease].
AB  - OBJECTIVE: To detect the pathogenic mutation in a Chinese family with Norrie
      disease. METHODS: Clinical diagnosis was based on familial history, clinical sign
      and B ultrasonic examination. Peripheral blood samples were obtained from all
      available members in a Chinese family with Norrie disease. Genomic DNA was
      extracted from lymphocytes by the standard SDS-proteinase K-phenol/chloroform
      method. Two coding exons and all intron-exon boundaries of the NDP gene were PCR
      amplified using three pairs of primers and subjected to automatic DNA sequence.
      The causative mutation was confirmed by restriction enzyme analysis and
      genotyping analysis in all members. RESULTS: Sequence analysis of NDP gene
      revealed a missense mutation c.220C > T (p.Arg74Cys) in the proband and his
      mother. Further mutation identification by restriction enzyme analysis and
      genotyping analysis showed that the proband was homozygote of this mutation. His
      mother and other four unaffected members (III3, IV4, III5 and II2) were carriers
      of this mutation. The mutant amino acid located in the C-terminal cystine knot
      like domain, which was critical motif for the structure and function of NDP.
      CONCLUSION: A NDP missense mutation was identified in a Chinese family with
      Norrie disease.

PMID- 23141578
TI  - [Choroidal thickness in normal subjects measured by enhanced depth imaging
      optical coherence tomography].
AB  - OBJECTIVE: To evaluate the efficiency of enhanced depth imaging optical coherence
      tomography (EDI-OCT) on quantifying choroidal thickness (CT) in normal subjects.
      METHODS: This was a cross-sectional study. From June to November 2011, 129 eyes
      of 129 normal subjects were enrolled in this study and divided into three groups
      by age distribution. Group A, 43 eyes, 22 to 40 years old; group B, 42 eyes, 41
      to 60 years old and group C, 44 eyes, 61 to 79 years old. They were examined with
      EDI-OCT for CT. The choroid was measured from the posterior edge of the retinal
      pigment epithelium to the choroid-scleral junction at 500 um intervals of a
      horizontal section from 3 mm temporal to the fovea to 3 mm nasal to the fovea.
      The paired t test was used to analyze differences in CT by location in the
      macula. One-way analysis of variance (ANOVA) was conducted to compare mean CT in
      different groups. Subsequently the data between two groups were analyzed by least
      significant difference (LSD-t). The reliability was evaluated by intraclass
      correlation coefficient (ICC). RESULTS: The choroid was thickest beneath the
      fovea (305.9 +/- 78.2) um. The mean CT decreased rapidly in the nasal direction
      and gradually in the temporal direction, reaching (159.0 +/- 67.3) um at 3 mm
      nasal to the fovea and (256.8 +/- 73.6) um at 3 mm temporal to the fovea. There
      was a significant difference between subfoveal CT and CT at all extrafoveal
      locations (t = 4.021 to 34.544, P < 0.05). There was also a significant
      difference of CT at all locations among three age groups (F = 34.122 to 72.239, P
      < 0.05). CT was significantly greater in group A than group B and C at all
      locations (P = 0.000, 0.000). It was also significantly greater in group B than
      group C (P = 0.000). The inter-examination ICC values ranged from 0.979 to 0.996.
      The intraobserver ICC values ranged from 0.981 to 0.997. The interobserver ICC
      values ranged from 0.971 to 0.995. CONCLUSIONS: Normal CT can be measured
      accurately by EDI-OCT. There are significant differences of CT between different
      age groups in normal subjects.

PMID- 23141579
TI  - [Effect of extract of Lycium barbarum L. on adult human retinal nerve cells].
AB  - OBJECTIVE: To study possible protective effects of extract of Lycium barbarum L.
      on the cultured human retinal nerve cells. METHODS: Retinal nerve cells were co
      cultured with the extract of Lycium barbarum L. and 24 hours and 72 hours later,
      retinal nerve cells were respectively used to evaluate cell proliferation with
      MTT assays; to observe ultracellular structural alternation with transmission
      electron microscopy (TEM) and to evaluate mitochondrial membrane potentials (MMP)
      of cells with confocal microscopy. The peaks of MMP between experiment group and
      control group were compared using one-way analysis of variance. RESULTS: Co
      cultured retinal nerve cells with the extract were shown survival well under the
      TEM including photoreceptor segments remaining well, abundant mitochondria in
      inner segments and well-distributed chromatin in photoreceptor nucleus (F =
      124.110, P < 0.05). The addition of the extract promoted survival of adult
      retinal neurons significantly in concentration-dependent manner with the
      strongest effect in 20 g/L. Cell survival rate (24 h and 72 h); (223.23 +/-
      12.13)% and (252.35 +/- 13.24)%. The peak of MMP increased 848% after the first
      adding of the extract (P = 0.000) and 1152% after the second adding of the
      extract (P = 0.000). It showed that the extract could enhance the MMP
      significantly with undulatory property. CONCLUSIONS: The extract of Lycium
      barbarum L. showed protective effects on cultured cells and could be used in
      treatment of some retinal diseases in future.

PMID- 23141580
TI  - [The cell-type-specific HSV-tk gene expression of suicide gene therapy system
      regulated by lens-specific promoter LEP503].
AB  - OBJECTIVE: To explore the specific expression of HSV-tk gene and killing effects
      on ocular leading cells of the enhanced specific HSV-tk/GCV gene therapy system
      regulated by lens-specific promoter LEP503. METHODS: Experimental research. The
      enhanced specific HSV-tk/GCV gene system of two vectors were constructed (Lenti
      LEP503-HSVtk-Cre and Lenti-HPGK-Loxp-EGFP-pA-Loxp-HSVtk). The lentiviral vectors
      were produced by transient transduction of transfering vectors, packaging vectors
      and enveloping vector into 293T cells. Virus was collected with
      ultracentrifugation and resuspended with 1 ml phosphate buffered saline and
      stored at -80 degrees C. The HLEC and RPEC, NIH3T3, 293T cells were transduced
      with the enhanced specific HSV-tk gene system. The specific expressions of EGFP
      and HSV-tk were detected by fluorescence microscopy, flow cytometry and RT-PCR.
      The killing effects of HLEC and RPEC at the concentration of 20 mg/L GCV were
      assayed and compared by flow cytometry and CCK-8 kit. Difference of RPE cell
      viability among groups was evaluated by analysis of variance (ANOVA). RESULTS:
      Expression efficiency of EGFP in RPEC group was 62.3%, 68.3% in NIH3T3 group,
      75.8% in 293T group, whereas 17.5% in HLEC group. There was higher expression of
      HSV-tk at mRNA level in HLEC group than that in RPEC group. The relative
      intensity of HSV-tk mRNA in HLEC group transduced with the enhanced specific HSV
      tk gene system was 4.01, whereas 0.29 in RPEC group. At the concentration of 20
      mg/L GCV after 72 hours, the percentage of apoptosis detected by the flow
      cytometry in HLEC group transduced by the enhanced specific HSV-tk gene system
      was 76.51%, and 2.44% in RPEC group. There was no significant difference in the
      RPE cell viability among the enhanced specific HSV-tk gene combination-RPE group,
      normal-RPE group and negative-RPE control group at the concentration of 20 mg/L
      GCV after 72 hours (MD(1) = -0.047, P = 0.671; MD(2) = 0.027, P = 0.912).
      CONCLUSIONS: The enhanced specific HSV-tk gene system express HSV-tk selectively
      in HLEC. At the concentration of 20 mg/L GCV, it is effective against the
      proliferation of HLEC in vitro, but has less kill effect on RPEC.

PMID- 23141581
TI  - [Retinal ganglion cell loss on APP/PS1 transgenic mice with Alzheimer's disease].
AB  - OBJECTIVE: To investigate the retinal nerve cell changes in number by tests on
      APP/PS1 double transgenic mice. METHODS: Experimental study. Comparison was made
      between 10 female 11-month-old APP/PS1 double transgenic mice with Alzheimer's
      disease (model group) and 10 non-transgenic female mice of the same background
      and age (control group). Retinal ganglion cell (RGC) was retrograde labeled by
      injecting horse radish peroxidase (HRP) into the bilateral optic nerve layer of
      the superior colliculus of two groups. After 48 hours, all mice were perfused
      sacrificed. The brains were frozen, mode slices, stained with methyl-alcohol
      Congo. The retina peeled from right eye was conducted HRP histochemistry reaction
      to count RGC by computerized image analyzer. The left eyes were treated with
      paraffin-embedded, mode slices, stained with hematoxylin and eosin (HE) to count
      the neuron numbers of each retina layers. The neuron numbers of each retina layer
      for control group and model group were statistically analyzed using t test for
      independent samples. RESULTS: The brains showed positive in the model group and
      the brains showed negative in the control group after stained with methyl-alcohol
      Congo. By counting retinal ganglion cells traced with HRP, the number of RGC was
      statistical different between two groups at 112.78 +/- 7.70 within per field for
      the control group against 78.72 +/- 11.35 within per field for the model group.
      The RGC of the model group was comparatively much less than the control group (t
      = 27.28, P < 0.01). By counting cells of retina stained with HE, the number of
      inner and outer nuclear layer cells were not statistical different between two
      groups of each layer (P > 0.05), the number of RGC in the control group and the
      model group were respectively 8.17 +/- 1.17 within per field, 5.17 +/- 0.75
      within per field. The cells in retinal ganglion layer in the model group were
      significantly reduced (t = 52.88, P < 0.01). CONCLUSION: The results imply that
      the number of RGC reduced in 11-month-old APP/PS1 double transgenic mice with
      Alzheimer's disease.

PMID- 23141582
TI  - [Clinical manifestations and treatment of Skew deviation].
AB  - Skew deviation is a vertical strabismus caused by supranuclear lesions. It is
      often associated with ocular torsion and head tilt, which together constitute the
      ocular tilt reaction. Skew deviation can result from any injury within the
      posterior fossa, and is often the initial manifestation of diseases that affect
      the brainstem, cerebellum, or peripheral vestibular system. Clinical subtypes
      include comitant, nonconcomitant, paroxysmal (intermittent), periodic or slowly
      alternating, lateral alternating and transient neonatal skew deviation. It should
      be differentiated from superior oblique muscle palsy, inferior oblique muscle
      palsy and primary oblique muscle overaction. Most skew deviations are transient
      and spontaneous recovery. Prisms, botulinum toxin, and vertical rectus muscle
      recession have all been used for vertical diplopia secondary to persistent skew
      deviation.

PMID- 23141583
TI  - [The application of serum free medium in the research of isolating cancer stem
      cells].
AB  - The isolation and identification of cancer stem cells are the key points in
      exploring characteristics of cancer stem cells at present. Several species of
      cancer stem cells, for instance, retinoblastoma tumor stem cells, cancer stem
      cells of melanoma of choroid, breast cancer stem cells, lung cancer stem cells,
      colon cancer stem cells, etc., have been isolated and cultured successfully by
      serum free medium while their biological functions and characteristics are
      acquired. This review focus on the application of serum free medium in the
      research of isolating cancer stem cells, both ocular and general, in terms of
      providing foundation for further research on ocular cancer stem cells.

PMID- 23141584
TI  - Determinants and clinical significance of plasma oxidized LDLs in older
      individuals. A 9 years follow-up study.
AB  - Oxidized LDLs (ox.LDLs) uptake by macrophages inside the arterial wall is a
      crucial step in atherosclerotic disease, and some studies suggest that high
      ox.LDLs plasma levels might be associated with cardiovascular disease (CVD).
      However, whether high ox.LDLs continue to be a CVD risk factors in older persons
      is unknown. We investigated the clinical correlates of plasma ox.LDLs, and their
      role in predicting long-term CVD/cardiac mortality in 1025 older community
      dwelling individuals (mean age: 75.5 +/- 7.4 years; females: 55%) from the
      InCHIANTI study. Kaplan-Meier curves were fitted to explore the relationship
      between tertiles of ox.LDLs (ox.LDL/LDL-C ratio) and time to CVD/cardiac death.
      Hazard Ratios (HR) were estimated by Cox regression analysis. At multivariate
      analysis, ox.LDLs were independently associated with LDL-C, triglycerides, and
      HDL-C (adjusted r(2): 0.42; P = 0.001). The ox.LDL/LDL-C ratio (the extent of
      LDLs oxidation) was independently correlated with HDL-C, triglycerides, and beta
      carotene (adjusted r(2): 0.15, P = 0.001). Among 1025 individuals, 392 died after
      9 years, 166 from CVD. The HR for CVD/cardiac mortality was not significantly
      different across tertiles of ox.LDLs or ox.LDL/LDL-C ratio, both in the whole
      sample and in individuals with prevalent CVD. We conclude that in an elderly
      population LDL-C, triglycerides, and HDL-C are the most important determinants of
      ox.LDLs levels, indirectly suggesting an association between small dense LDLs and
      LDLs oxidation. No association emerged between higher ox.LDLs levels and 9 years
      CVD/cardiac mortality, suggesting that in advanced age the prognostic information
      added by ox.LDLs on CVD/cardiac mortality might be negligible.

PMID- 23141585
TI  - Pomegranate phytosterol (beta-sitosterol) and polyphenolic antioxidant
      (punicalagin) addition to statin, significantly protected against macrophage foam
      cells formation.
AB  - OBJECTIVE: To assess the anti-atherogenic effects on macrophage cholesterol
      biosynthesis rate, and on cellular oxidative stress by the combination of
      simvastatin with a potent polyphenolic antioxidant (punicalagin), or with a
      phytosterol (beta-sitosterol), or with pomegranate juice (POM, that contains both
      of them). METHODS AND RESULTS: Simvastatin (15 MUg/ml) decreased J774A.1
      macrophage cholesterol biosynthesis rate by 42% as compared to control cells. The
      addition to the statin of either punicalagin (15 or 30 MUM), or beta-sitosterol
      (50 or 100 MUM), increased the inhibitory effect of the statin up to 62% or 57%,
      respectively. Similarly, the combination of POM and simvastatin, resulted in an
      inhibitory effect up to 59%. While simvastatin inhibited the rate limiting enzyme
      HMGCoA-reductase, punicalagin, beta-sitosterol or POM inhibited macrophage
      cholesterol biosynthesis downstream to mevalonate. Simvastatin (15 MUg/ml) also
      modestly decreased macrophage reactive oxygen species (ROS) formation by 11%. In
      the presence of punicalagin (15 or 30 MUM) however, a remarkable further
      inhibition was noted (by 61% or 79%, respectively). Although beta-sitosterol
      alone showed some pro-oxidant activity, the combination of simvastatin, beta
      sitosterol and punicalagin, clearly demonstrated a remarkable 73% reduction in
      ROS production. Similarly, simvastatin + POM decreased the extent of ROS
      formation by up to 63%. These improved antioxidant effects of the combinations
      could be related to various anti-oxidative properties of the different compounds,
      including free radicals scavenging capacity, upregulation of paraoxonase 2, and
      stimulation of reduced glutathione. CONCLUSION: The combination of simvastatin
      with potent antioxidant and phytosterol (such as present in pomegranate) could
      lead to attenuation of macrophage foam cell formation and atherogenesis.

PMID- 23141586
TI  - The effect of obesity on the association between liver fat and carotid
      atherosclerosis in a multi-ethnic cohort.
AB  - OBJECTIVE: Non-alcoholic fatty liver disease is the most common liver disorder in
      Western society, increasing in parallel with obesity and the metabolic syndrome.
      Evidence suggests that there is an independent relationship between liver fat
      (LF) and atherosclerosis, however it is unknown if this applies to low risk
      populations. The purpose of this study was to evaluate the association between LF
      and measures of sub-clinical carotid atherosclerosis in men and women of
      Aboriginal, Chinese, European, and South Asian origin. METHODS AND RESULTS:
      Healthy men and women were assessed for LF (computed tomography scan) and
      atherosclerosis (carotid ultrasound) in addition to cardiovascular risk factors,
      demographics, and body composition. Liver Hounsfield units (HU) values were
      negatively correlated with age, BMI, waist circumference (WC), percent body fat,
      carotid intima media thickness total plaque area, and total area. LF was
      significantly associated with carotid IMT and total area after adjustment for
      sex, age, ethnicity, education, income and smoking status. However after
      adjusting for BMI and WC, LF was no longer significantly associated with
      atherosclerosis. CONCLUSION: Increased LF may be associated with atherosclerosis,
      however, after adjustment for body composition, LF was not significantly
      associated with sub-clinical atherosclerosis. BMI and WC are useful
      anthropometric measures for the evaluation of CVD risk independent of LF.

PMID- 23141587
TI  - Borrelia burgdorferi infection and Lyme disease in children.
AB  - Lyme disease is a multisystem disease that frequently affects children. It is
      caused by a group of related spirochetes, Borrelia burgdorferi sensu lato, that
      are transmitted by ticks belonging to species of the genus Ixodes. The clinical
      characteristics of Lyme disease in pediatrics resemble those observed in adults,
      although the symptoms may last for a shorter time and the outcome may be better.
      However, identifying Lyme disease in children can be significantly more difficult
      because some of its signs and symptoms can be similar to those of other common
      pediatric clinical manifestations. Finally, the diagnostic and therapeutic
      approach to childhood Lyme disease is frequently not codified, and guidelines
      specifically prepared for adults are used for children without having been
      validated. This review of the currently available data will evaluate what may be
      the best approach to the diagnosis and treatment of B. burgdorferi infection and
      disease in the pediatric population.

PMID- 23141588
TI  - Substrate specificity of Tulane virus protease.
AB  - Tulane virus (TV) is a cultivable calicivirus isolated from rhesus monkeys. In
      this study, we characterized the substrate specificity of TV protease in trans
      using recombinant proteases and TV polyprotein fragments containing the predicted
      proteolytic cleavage sites. Cleavage products have been obtained from 4 of the 5
      fragments containing (573)Q-S(574) between the helicase and 3A-like protein,
      (712)E-A(713) between the 3A-like protein and Vpg, (802)E-G(803) between Vpg and
      the protease, and (976)E-G(977) between the protease and RdRp. We also
      characterized the enzymatic activities of the recombinant proteases of TV and
      Norwalk virus using synthetic fluorogenic peptide substrates. Under optimal
      conditions for enzymatic assays, partial cross-reactivities on reciprocal
      substrates were observed between TV and Norwalk virus proteases. The apparently
      shared substrate specificities between TV and Norwalk virus proteases suggested
      that the cultivable TV could be used as a model for in vivo evaluation of lead
      candidates of protease inhibitors for human norovirus.

PMID- 23141590
TI  - [In law, the other].

PMID- 23141591
TI  - [Access to Assisted Reproductive Technologies, surrogacy, same sex couple
      parenting].
AB  - In France, access to Assisted Reproductive Technologies (ART) is strictly
      controlled. ART is only authorized for medical infertility. The revision of the
      law of bioethics has not modified access to ART. It is still forbidden to take
      charge of lesbian couples or gay-male couples, surrogacy is prohibited. The only
      change is that unmarried couples have no more to prove they live together since 2
      years.

PMID- 23141589
TI  - Is treatment adherence consistent across time, across different treatments and
      across diagnoses?
AB  - OBJECTIVE: The objective was to examine consistency of adherence across
      depression treatments and consistency of adherence between depression treatments
      and treatments for chronic medical illness. METHODS: For 25,456 health plan
      members beginning psychotherapy for depression between 2003 and 2008, health plan
      records were used to examine adherence to all episodes of psychotherapy,
      antidepressant medication, antihypertensive medication and lipid-lowering
      medication. RESULTS: Within treatments, adherence to psychotherapy in one episode
      predicted approximately 20% greater likelihood of subsequent psychotherapy
      adherence [odds ratio (OR)=2.20, 95% confidence interval (CI) 1.83-2.64].
      Similarly, adherence to antidepressant medication in one episode predicted
      approximately 20% greater likelihood of subsequent antidepressant adherence
      (OR=1.99, 95% CI 1.74-2.28). Across treatments, adherence to antidepressant
      medication predicted approximately 10% greater likelihood of concurrent or
      subsequent adherence to psychotherapy (OR=1.52, 95% CI 1.42-1.63), a 4% greater
      likelihood of adherence to antihypertensive medication (OR=1.24, 95% CI 1.14
      1.37) and a 3% greater likelihood of adherence to lipid-lowering medication
      (OR=1.16, 95% CI 1.03-1.32). Adherence to psychotherapy predicted a 2% greater
      likelihood of concurrent or subsequent adherence to antihypertensive medication
      (OR=1.11, 95% CI 1.04-1.19) and was not a significant predictor of adherence to
      lipid-lowering medication (OR=0.99, 95% CI 0.90-1.18). CONCLUSIONS: Adherence is
      moderately consistent across episodes of depression treatment. Depression
      treatment adherence is a statistically significant, but relatively weak,
      predictor of adherence to antihypertensive or lipid-lowering medication.

PMID- 23141592
TI  - [Anonymity and gamete donation].
AB  - In France the gamete donation is based on the major principles: anonymity, no
      payment, solidarity and this mode of procreation can be used only if a medical
      indication is present in recipient couples. In prerequisite and during the
      revision of the law of bioethics, a wide debate took place about the anonymity of
      gamete donation. The objectives of this article is to review the concept of the
      anonymity and its links with the questions of the origin, the secret of the
      modalities of the conception and the mourning of the fertility, children, donors
      and the recipient couples waiting for gamete donation. The international
      situation is also addressed. The contribution of the CECOS, the centers which
      practice the sperm and the egg donations is highlighted. The anonymity cannot be
      discussed without addressing all these links and the complexity of this
      particular mode of conception. To date, the French society has maintained the
      anonymity in the new law of bioethics.

PMID- 23141593
TI  - [Embryo and stem cells researches: before and after the bioethics law of 2011].
AB  - The bioethics law of 2004 prohibited any research on the human embryo but
      authorized by way of derogation this one. The French biomedicine agency was
      charged to take care of the scientific, legal respect and ethics of this
      research, via its council of orientation. In 5 years it took more than 100
      decisions on this subject. Although the discussions for the revision were
      important these last years, the new law of bioethics of July 7th, 2011 does not
      change anything with regard to research on the embryo and the stem cells.

PMID- 23141594
TI  - [Posthumous assisted reproductive technologies].
AB  - Several types of posthumous ART, all exceptional, can be considered. Using frozen
      sperm by the wife or concubine results in a conception at a time when the father
      has been dead for longer or shorter. His ban is broadly consensual in France.
      Transferring frozen embryos after the man's death raises more questions. The only
      options in France for the surviving wife are donation to another couple, donation
      to research or destruction. The National Consultative Ethics Committee was
      several times favourable to allowing this practice under certain conditions, but
      it is still prohibited after the 2011 revision of the bioethics laws.

PMID- 23141595
TI  - [Vitrification of oocytes and embryos: the law, the results, the future].
AB  - The French bio ethical law published in 2004 did not authorize the transfer of
      embryos submitted to a research program, or even issued from gametes concerned by
      an experimentation. Vitrification process was still considered as an
      "experimental" technique; thus it was impossible to vitrify either oocytes or
      embryos, whereas numerous international studies emphasized the interest of this
      technique for both oocytes and embryos, in particular if they were vitrified at
      the blastocyst stage. The new revised law (7/7/2011), clearly authorizes oocyte
      vitrification; moreover, studies intended to improve ART efficiency, are now
      permitted, enabling vitrification of embryos.

PMID- 23141596
TI  - [Legislative and regulatory situation of oocytes donation in France].
AB  - In France, medically assisted procreation (MAP) activities and gamete donation
      are strictly regulated by the bioethics law. The main ethical principles applied
      to the donation--no remuneration, anonymity, and the requirement for free and
      informed consent--aim to protect donors. In the same spirit, since MAP with
      oocytes donation is recognized as a healthcare activity, receiving couples
      benefit from exemption from co-payments by the health insurance system. Thus, it
      is widely accessible to couples presenting medical infertility requiring oocytes
      from a donor, but availability is insufficient to cover needs. This shortage in
      supply results in moving the demand abroad where this particular MAP is exercised
      at varying levels of supervision.

PMID- 23141598
TI  - Promising strategies for Gd-based responsive magnetic resonance imaging contrast
      agents.
AB  - Magnetic resonance imaging is a powerful imaging modality that is often coupled
      with paramagnetic contrast agents based on gadolinium to enhance sensitivity and
      image quality. Responsive contrast agents are key to furthering the diagnostic
      potential of MRI, both to provide anatomical information and to discern
      biochemical activity. Recent design of responsive gadolinium-based T1 agents has
      made interesting progress, with the development of novel complexes which sense
      their chemical environment through changes in the coordination of water
      molecules, the molecular tumbling time or the number of metal centres. Particular
      promising design strategies include the use of multimeric systems, and the
      development of dual imaging probes.

PMID- 23141597
TI  - Recent advances in protein prenyltransferases: substrate identification,
      regulation, and disease interventions.
AB  - Protein post-translational modifications increase the functional diversity of the
      proteome by covalently adding chemical moieties onto proteins thereby changing
      their activation state, cellular localization, interacting partners, and life
      cycle. Lipidation is one such modification that enables membrane association of
      naturally cytosolic proteins. Protein prenyltransferases irreversibly install
      isoprenoid units of varying length via a thioether linkage onto proteins that
      exert their cellular activity at membranes. Substrates of prenyltransferases are
      involved in countless signaling pathways and processes within the cell.
      Identification of new prenylation substrates, prenylation pathway regulators, and
      dynamic trafficking of prenylated proteins are all avenues of intense, ongoing
      research that are challenging, exciting, and have the potential to significantly
      advance the field in the near future.

PMID- 23141599
TI  - Bringing postnatal depression out of the shadows.

PMID- 23141600
TI  - The right to cervical cancer services in southern Africa.

PMID- 23141601
TI  - Media relations: work in progress.

PMID- 23141602
TI  - Progress and challenges in bacterial meningitis.

PMID- 23141605
TI  - The UN needs joined-up thinking on vital registration.

PMID- 23141606
TI  - Health workers and universal health coverage.

PMID- 23141607
TI  - User fees in universal health systems.

PMID- 23141608
TI  - Universal health-care coverage in Europe.

PMID- 23141609
TI  - Universal health-care coverage in Europe.

PMID- 23141611
TI  - Polio vaccination in Pakistan.

PMID- 23141612
TI  - Global Fund at risk of alienating civil society.

PMID- 23141614
TI  - Safeguarding language, accuracy, and good science.

PMID- 23141613
TI  - Global health in the UK's GP postgraduate curriculum.

PMID- 23141615
TI  - Vaccination for whom? Time to reinvigorate Japanese vaccine policy.

PMID- 23141616
TI  - On the road to the insulin centenary.

PMID- 23141617
TI  - Dilemmas in the diagnosis of acute community-acquired bacterial meningitis.
AB  - Rapid diagnosis and treatment of acute community-acquired bacterial meningitis
      reduces mortality and neurological sequelae, but can be delayed by atypical
      presentation, assessment of lumbar puncture safety, and poor sensitivity of
      standard diagnostic microbiology. Thus, diagnostic dilemmas are common in
      patients with suspected acute community-acquired bacterial meningitis. History
      and physical examination alone are sometimes not sufficient to confirm or exclude
      the diagnosis. Lumbar puncture is an essential investigation, but can be delayed
      by brain imaging. Results of cerebrospinal fluid (CSF) examination should be
      interpreted carefully, because CSF abnormalities vary according to the cause,
      patient's age and immune status, and previous treatment. Diagnostic prediction
      models that use a combination of clinical findings, with or without test results,
      can help to distinguish acute bacterial meningitis from other causes, but these
      models are not infallible. We review the dilemmas in the diagnosis of acute
      community-acquired bacterial meningitis, and focus on the roles of clinical
      assessment and CSF examination.

PMID- 23141618
TI  - Advances in treatment of bacterial meningitis.
AB  - Bacterial meningitis kills or maims about a fifth of people with the disease.
      Early antibiotic treatment improves outcomes, but the effectiveness of widely
      available antibiotics is threatened by global emergence of multidrug-resistant
      bacteria. New antibiotics, such as fluoroquinolones, could have a role in these
      circumstances, but clinical data to support this notion are scarce. Additionally,
      whether or not adjunctive anti-inflammatory therapies (eg, dexamethasone) improve
      outcomes in patients with bacterial meningitis remains controversial; in resource
      poor regions, where the disease burden is highest, dexamethasone is ineffective.
      Other adjunctive therapeutic strategies, such as glycerol, paracetamol, and
      induction of hypothermia, are being tested further. Therefore, bacterial
      meningitis is a substantial and evolving therapeutic challenge. We review this
      challenge, with a focus on strategies to optimise antibiotic efficacy in view of
      increasingly drug-resistant bacteria, and discuss the role of current and future
      adjunctive therapies.

PMID- 23141619
TI  - Effect of vaccines on bacterial meningitis worldwide.
AB  - Three bacteria--Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria
      meningitidis--account for most acute bacterial meningitis. Measurement of the
      effect of protein-polysaccharide conjugate vaccines is most reliable for H
      influenzae meningitis because one serotype and one age group account for more
      than 90% of cases and the incidence has been best measured in high-income
      countries where these vaccines have been used longest. Pneumococcal and
      meningococcal meningitis are caused by diverse serotypes and have a wide age
      distribution; measurement of their incidence is complicated by epidemics and
      scarcity of surveillance, especially in low-income countries. Near elimination of
      H influenzae meningitis has been documented after vaccine introduction. Despite
      greater than 90% reductions in disease attributable to vaccine serotypes, all-age
      pneumococcal meningitis has decreased by around 25%, with little data from low
      income settings. Near elimination of serogroup C meningococcal meningitis has
      been documented in several high-income countries, boding well for the effect of a
      new serogroup A meningococcal conjugate vaccine in the African meningitis belt.

PMID- 23141620
TI  - The sound of silence.

PMID- 23141621
TI  - Analysis of linear and cyclic methylsiloxanes in sewage sludges and urban soils
      by concurrent solvent recondensation-large volume injection-gas chromatography
      mass spectrometry.
AB  - Concurrent solvent recondensation-large volume injection (CSR-LVI) is a gas
      chromatography injection technique that is particularly suitable for determining
      volatile compounds. In the present work, we evaluated the applicability of this
      technique for the analysis of linear and cyclic methylsiloxanes in sewage sludges
      and soils after solvent extraction to prevent losses of low-molecular-weight
      compounds. The CSR-LVI injection method was optimised to achieve maximum
      sensitivity and good chromatographic peak shapes. A liner packed with deactivated
      glass wool and a 5 m * 0.32 mm I.D. uncoated fused-silica precolumn was used.
      This made it possible to inject extract volumes of up to 30 MUl. Good linearity
      (r>0.9993) and precision (RSD <15%), with recoveries ranging from 80 to 100% and
      method limits of quantification from 0.03 to 0.4 ng g(-1) wet weight (0.04-1.5 ng
      g(-1) dry weight for sewage sludges and 0.01-0.5 ng g(-1) dry weight for soils)
      were obtained. The developed method was applied to the analysis of linear and
      cyclic methylsiloxanes in sewage sludges collected from several wastewater
      treatment plants in Catalonia (NE Spain) and urban soils from the city of
      Barcelona.

PMID- 23141622
TI  - Chiral speciation and determination of selenomethionine enantiomers in selenized
      yeast by ligand-exchange micellar electrokinetic capillary chromatography after
      solid phase extraction.
AB  - A new phenylalanine derivative (L-N-(2-hydroxy-propyl)-phenylalanine, L-HP-Phe)
      was synthesized and its chelate with Cu(II) (Cu(II)-(L-HP-Phe)(2)) was used as
      the chiral selector for the ligand-exchange (LE) chiral separation of D,L
      selenomethionine (SeMet) in selenized yeast samples by micelle electrokinetic
      capillary chromatography (MEKC). In order to improve the sensitivity of MEKC-UV,
      two-step preconcentration strategy was employed, off-line solid phase extraction
      (SPE) and on-line large volume sample stacking (LVSS). D,L-SeMet was first
      retained on the Cu(II) loaded mesoporous TiO(2), then eluted by 0.1 mL of 5 mol
      L(-1) ammonia, and finally introduced for MEKC-UV analysis by LVSS injection
      after evaporation of NH(3). With the enrichment factors of 1400 and 1378, the
      LODs of 0.44 and 0.60 ng mL(-1) for L-SeMet and D-SeMet was obtained,
      respectively. The developed method was applied to the analysis of D,L-SeMet in a
      certified reference material of SELM-1 and a commercial nutrition yeast, and the
      results showed that most of SeMet in the SELM-1 selenized yeast was l isomer and
      the recovery for L and D isomers in the spiked commercial nutrition yeast was
      96.3% and 103%, respectively. This method is featured with low running cost, high
      sensitivity and selectivity, and exhibits application potential in chiral
      analysis of seleno amino acids in real world samples.

PMID- 23141623
TI  - Separation of Sudan dyes from chilli powder by magnetic molecularly imprinted
      polymer.
AB  - A simple method based on magnetic molecularly imprinted polymers (MMIPs) for the
      separation of Sudan dyes from chilli powder samples has been developed. The MMIPs
      were synthesized as follows: the Fe(3)O(4) nanoparticles were encapsulated with a
      SiO(2) shell and functionalized with -CH=CH(2), then the polymers were further
      fabricated by surface-imprinted polymerization using Sudan IV as template
      molecule, methacrylic acid as functional monomer, and ethylene glycol
      dimethacrylate as cross-linking agent. The prepared MMIPs were characterized by
      scanning electron microscope, Fourier transform infrared spectrometry and
      physical property measurement system. The isothermal absorption experiment,
      kinetics absorption experiment and selectivity of MMIPs were tested. The analytes
      were determined by high performance liquid chromatography. Under the optimal
      conditions, the limits of detection of the four Sudan dyes are 6.2, 1.6, 4.3 and
      4.5 ng g(-1), respectively. The precision expressed as relative standard
      deviation ranging from 4.8% to 9.1% was obtained. In all three fortified levels
      (25, 250 and 2500 ng g(-1)), recoveries of Sudan dyes were in the range of 79.9
      87.8%.

PMID- 23141624
TI  - Dispersive liquid-liquid microextraction prior to field-amplified sample
      injection for the sensitive analysis of 3,4-methylenedioxymethamphetamine,
      phencyclidine and lysergic acid diethylamide by capillary electrophoresis in
      human urine.
AB  - A novel capillary zone electrophoresis (CZE) with ultraviolet detection method
      has been developed and validated for the analysis of 3,4
      methylenedioxymethamphetamine (MDMA), lysergic acid diethylamide (LSD) and
      phencyclidine (PCP) in human urine. The separation of these three analytes has
      been achieved in less than 8 min in a 72-cm effective length capillary with 50
      MUm internal diameter. 100 mM NaH(2)PO(4)/Na(2)HPO(4), pH 6.0 has been employed
      as running buffer, and the separation has been carried out at temperature and
      voltage of 20 degrees C, and 25kV, respectively. The three drugs have been
      detected at 205 nm. Field amplified sample injection (FASI) has been employed for
      on-line sample preconcentration. FASI basically consists in a mismatch between
      the electric conductivity of the sample and that of the running buffer and it is
      achieved by electrokinetically injecting the sample diluted in a solvent of lower
      conductivity than that of the carrier electrolyte. Ultrapure water resulted to be
      the better sample solvent to reach the greatest enhancement factor. Injection
      voltage and time have been optimized to 5 kV and 20s, respectively. The
      irreproducibility associated to electrokinetic injection has been correcting by
      using tetracaine as internal standard. Dispersive liquid-liquid microextraction
      (DLLME) has been employed as sample treatment using experimental design and
      response surface methodology for the optimization of critical variables. Linear
      responses were found for MDMA, PCP and LSD in presence of urine matrix between
      10.0 and 100 ng/mL approximately, and LODs of 1.00, 4.50, and 4.40 ng/mL were
      calculated for MDMA, PCP and LSD, respectively. The method has been successfully
      applied to the analysis of the three drugs of interest in human urine with
      satisfactory recovery percentages.

PMID- 23141625
TI  - [Neurolysis of the median nerve in the elderly: a long term evaluation].
AB  - PURPOSE: Carpal tunnel release by opening the flexor retinaculum is considered a
      satisfactory treatment. However, several factors, like ageing, may influence
      postoperative results. We present the long term outcomes in elderly patients.
      METHODS: This is an historical prospective long term study of 52 patients who
      received surgical treatment of carpal tunnel syndrome when they were 65 or older.
      We have carried out a clinical-functional (with the Levine questionnaire),
      electromyographic and dynamometric valuation of the patients studied, up to ten
      years from the surgery. RESULTS: The results of Levine's questionnaire, revealed
      favourable data for a mean follow-up of 10.35 years, with a mean improvement in
      the clinical score of 1.93 points (95% confidence interval [CI]: 1.72-2.17) and
      in the functional score of 0.83 points (95% CI: 0.68-0.99). Similarly, the
      electromyographic values showed a significant improvement compared to
      preoperative ones (mean difference of sensory velocity of 8.43m/s, 95% CI: 8.17
      11.63; mean difference of motor latency of 1.65ms, 95% CI: 1.24-2.25). The data
      on grip strength did not reach statistical significance. CONCLUSIONS: In elderly
      patients, complete section of the carpal transverse ligament, allows maintaining
      favourable differences in most of the parameters studied, ten years after
      surgery, making the surgical treatment a recommendable option.

PMID- 23141626
TI  - [Opening of an Acute Orthogeriatric Unit in a general hospital].
AB  - BACKGROUND: Patients with hip fracture (HF), due to their characteristics,
      require a specific support. The Acute Orthogeriatric Unit (OGU) has been shown to
      be one of the most beneficial. OBJECTIVE: To evaluate the main variables of HF
      patients treated at an OGU and compare them with the previous referral model
      (RC). MATERIAL AND METHODS: A prospective observational study with retrospective
      control was conducted on 169 patients, split into two groups. In the RC group,
      patients were admitted to conventional trauma ward. In the OGU group, an early
      geriatric assessment was performed, and patients were simultaneously attended
      daily by the orthopaedic surgeon, nurse and geriatrician, and the surgery times,
      work load, discharge and destination, were planned in a weekly meeting with the
      rest of professionals. RESULTS: A total of 71 patients were included in the RC
      group and 96 in the OGU group. The preoperative characteristics were similar,
      except for a slightly higher comorbidity in the OGU group. The OGU patients were
      operated on earlier (3.82+/-2.08 vs 4.61+/-2.5 days; P<.32), and overall hospital
      stay was reduced by 28% (11.84+/-4.04 vs 16.46+/-8.4 days; P<.001). The
      functional efficiency (Barthel Index at discharge-Barthel Index at
      admission/overall stay - stay before surgery) was higher in the OGU group (1.56+/
      0.7 vs 2.61+/-1.1; P<.05). There were no differences in functional status,
      mortality or discharge location. CONCLUSIONS: The OGU is a level of care that
      provides effective medical care in HF patients in general hospitals.

PMID- 23141627
TI  - Challenges after the first decade of transcatheter aortic valve replacement:
      focus on vascular complications, stroke, and paravalvular leak.
AB  - Transcatheter aortic valve replacement (TAVR) is entering its second decade.
      Three major clinical challenges have emerged from the first decade of experience:
      vascular complications, stroke, and paravalvular leak (PVL). Major vascular
      complications remain common and independently predict major bleeding,
      transfusion, renal failure, and mortality. Although women are more prone to
      vascular complications, overall they have better survival than men. Further
      predictors of major vascular complications include heavily diseased femoral
      arteries and operator experience. Strategies to minimize vascular complications
      include a multimodal approach and sleeker delivery systems. Although cerebral
      embolism is very common during TAVR, it mostly is asymptomatic. Major stroke
      independently predicts prolonged recovery and increased mortality. Identified
      stroke predictors include functional disability, previous stroke, a transapical
      approach, and atrial fibrillation. Embolic protection devices are in development
      to mitigate the risk of embolic stroke after TAVR. PVL is common and
      significantly decreases survival. Undersizing of the valve prosthesis can be
      minimized with 3-dimensional imaging by computed tomography or echocardiography
      to describe the elliptic aortic annulus accurately. The formal grading of PVL
      severity in TAVR is based on its percentage of the circumferential extent of the
      aortic valve annulus. Further emerging management strategies for PVL include a
      repositionable valve prosthesis and transcatheter plugging. The first decade of
      TAVR has ushered in a new paradigm for the multidisciplinary management of
      valvular heart disease. The second decade likely will build on this wave of
      initial success with further significant innovations.

PMID- 23141628
TI  - Isoflurane prevents neurocognitive dysfunction after cardiopulmonary bypass in
      rats.
AB  - OBJECTIVE: Postoperative cognitive dysfunction occurs frequently after cardiac
      surgeries with cardiopulmonary bypass (CPB). Available data from rat CPB models
      are conflicting. However, none of them was designed to investigate the role of
      isoflurane (the main anesthetic in all of these studies) in the neurocognitive
      dysfunction after CPB. Isoflurane has documented neuroprotective effects so the
      present authors hypothesized that isoflurane prevents the neurocognitive
      dysfunction in rats after CPB. DESIGN: A prospective, interventional study.
      SETTING: A university research laboratory. PARTICIPANTS: Male Sprague-Dawley
      rats. INTERVENTIONS: Male Sprague-Dawley rats were divided into 5 groups: the
      isoflurane CPB group, the animals were anesthetized with isoflurane and underwent
      60 minutes of normothermic CPB; the chloral hydrate CPB group, the animals were
      anesthetized with chloral hydrate and underwent 60 minutes of normothermic CPB;
      the isoflurane sham group, the animals were subjected only to cannulation and the
      same duration of anesthesia but no CPB; the chloral hydrate sham group, the
      animals received only cannulation and the same duration of anesthesia but no CPB;
      and the naive group, the animals received no treatment. The neurocognitive
      function of all rats was measured on days 4 to 6 (short-term) and 31 to 33 after
      CPB (long-term). After the behavior tests, the animals were sacrificed, and the
      brain was harvested for the measurement of acetylcholinesterase (AChE) and
      choline acetyltransferase protein levels. MEASUREMENTS AND MAIN RESULTS: Short
      term (days 4-6 after CPB) learning and memory were impaired after CPB when the
      animals were anesthetized with chloral hydrate. When isoflurane was used, the
      learning and memory did not change after CPB. No long-term (days 31-33 after CPB)
      neurocognitive changes were found after CPB. AChE decreased significantly after
      isoflurane anesthesia regardless of whether CPB was performed. CONCLUSIONS:
      Isoflurane prevented the neurocognitive dysfunction induced by CPB, which might
      involve the cerebral cholinergic system.

PMID- 23141629
TI  - The elusive role of L-glutamate as an echinoderm neurotransmitter: evidence for
      its involvement in the control of crinoid arm muscles.
AB  - Although l-glutamate is the most widespread excitatory neurotransmitter in
      vertebrate and invertebrate nervous systems, there is only sparse evidence that
      it has this role in echinoderms. Following our previous finding that l-glutamate
      is widely distributed in the arms of the featherstar (crinoid echinoderm) Antedon
      mediterranea and initiates arm autotomy (defensive detachment), we now provide
      evidence of glutamatergic involvement in the control of the arm muscles of the
      same species using immunocytochemical and physiological methods.
      Immunofluorescence and immunoenzymatic techniques, which employed the same
      polyclonal antibody against l-glutamate conjugated to glutaraldehyde, revealed a
      high level of glutamate-like reactivity in the brachial muscles. By recording the
      mechanical responses of isolated arm pieces, we found that l-glutamate, l
      aspartate and elevated [K(+)](o) induced rhythmic muscle contractions, while
      glycine, gamma-aminobutyric acid, adrenaline and acetylcholine had either no, or
      no consistent, effect. The frequency and duration of the dominant component of
      the rhythmic contractions indicated that these may be responsible for the
      rhythmic activity of the arms that occurs during swimming and after autotomy. We
      conclude that it is highly likely that l-glutamate has at least a neuromodulatory
      role in the neural pathways controlling the brachial muscles of A. mediterranea.

PMID- 23141630
TI  - Costs of the principal mood disorders: a study of comparative direct and indirect
      costs incurred by those with bipolar I, bipolar II and unipolar disorders.
AB  - BACKGROUND: While there have been many studies comparing direct and indirect
      costs engendered individually and nationally by those with unipolar (UP) and
      bipolar (BP) disorders, there has been no previous study comparing costs across
      the bipolar I (BP I) and bipolar II (BP II) disorders. METHODS: We examine direct
      and indirect costs attributable to a mood disorder in a sample of 44 BP I, 102 BP
      II and 279 UP patients attending a tertiary referral clinic, and with comparable
      illness durations of some 20 years and comparable treatment durations. We
      calculated direct and indirect costs incurred for their lifetime of illness based
      on relevant cost structures, in Australian dollars. RESULTS: The mean lifetime
      indirect costs for BP I patients was $134,318, as against $76,821 for BP II and
      $68,347 for UP patients, joining with respective health care costs of $26,353,
      $17,580 and $27, 237, to generate total costs of $160,671/BP I patient,
      $94,401/BP II patient and $95,584/UP patient. BP I patients differentiated most
      distinctly in costs as a consequence of a higher prevalence of government
      benefits, time off work and longer periods in hospital. UP patients had more
      stable work histories than both BP sub-sets. BP II patients were less likely to
      be hospitalised than both the BP I and UP patients. LIMITATIONS: Being drawn from
      a tertiary referral clinic, the study sample is not necessarily representative,
      with this nuance potentially having influenced cost differences between groups.
      CONCLUSIONS: This is the first cost of illness study directly comparing BP I and
      BP II patients (and with an additional comparison group of UP patients). Findings
      indicate that BP I illness generates more direct and indirect costs than BP II
      illness, while the latter was generally comparable with UP depression in terms of
      the lifetime cost.

PMID- 23141631
TI  - Neurocognitive functioning in the prodrome of mania--an exploratory study.
AB  - BACKGROUND: Cognitive deficits have been well documented in individuals with
      bipolar disorder (BD) after the first episode of mania. However, little is known
      about the presence of such deficits prior to the initial manic episode. METHODS:
      Participants were recruited from a cohort of 416 young people who were at ultra
      high risk (UHR) for psychosis and were followed up between 4 and 13 years later.
      The current report is of 16 participants who developed BD over a mean follow-up
      period of 8.2 years (UHR-BD). Baseline demographic, clinical and neurocognitive
      assessment scores were compared with those of 46 age and gender matched UHR
      subjects who did not transition to psychosis or BD over the follow-up period (UHR
      NT) and 66 healthy comparison subjects. RESULTS: UHR-BD subjects had lower global
      functioning at baseline compared with UHR-NT subjects. There were no significant
      differences between UHR-BD and UHR-NT subjects on baseline demographic and
      neurocognitive characteristics. UHR-BD subjects had lower test performance than
      HC on picture completion, Trail-Making Tests and measures of global intelligence.
      LIMITATIONS: Small sample size, limited and variable neurocognitive tests
      utilised and the confounding effects of psychotic symptoms might have impacted on
      the ability to detect meaningful clinical and neurocognitive differences.
      CONCLUSIONS: In this exploratory study, neurocognition in young people who later
      develop BD is similar to those of subjects who are at a high risk for psychotic
      disorders, but there may be certain neurocognitive markers that distinguish this
      group from unaffected and healthy young people.

PMID- 23141632
TI  - Differentiating disordered affect in children and adolescents with type 1
      diabetes.
AB  - BACKGROUND: There is evidence for increased risk of affective disorders (AD) in
      adults with type 1 diabetes however, the prevalence and characteristics of AD in
      young people with the condition is unclear. Comorbid AD in type 1 diabetes is
      associated with deleterious self-management, sub-optimal clinical indicators,
      reduced quality of life, poorer physical health, increased complications,
      increased high risk behaviours in adolescence and young adulthood, and earlier
      mortality. The present study investigated the prevalence and character of AD in
      young people with type 1 diabetes. METHODS: The self-report PH-PANAS-C was
      employed in a cross-sectional, case-control design to identify and differentiate
      full-syndrome (FS) and subthreshold (St) levels of AD in 53 participants with
      type 1 diabetes (case) and 54 age-balanced controls (N=107; 7-18 yrs). RESULTS:
      Case participants reported greater AD than controls. When differentiated, only
      anxiety was significantly more prevalent. Case participants reported less
      positive affect, and greater negative affect and autonomic arousal. Further, 1:3
      case participants presented with St symptoms of AD. LIMITATIONS: Self-report
      measures are known to produce moderated responses therefore symptoms may be more
      severe than reported. There has been some suggestion that responses to somatic
      items in the PH-PANAS-C may relate to diabetes-specific states rather than affect
      related symptoms however, recent evidence has refuted this argument. CONCLUSIONS:
      AD, particularly anxiety, represents a significant clinical concern in young
      people with type 1 diabetes both as a disorder in its own right and as a major
      impediment to primary care and management of the diabetes. The significant
      dominance of anxiety-related symptoms and prevalence of subthreshold presentation
      warrant further investigation.

PMID- 23141633
TI  - Clinical and polysomnographic correlation in sleep-related breathing disorders in
      children.
AB  - INTRODUCTION: Although polysomnography is the gold standard test for sleep
      disordered breathing in children, there is controversy about its indication in
      all cases. Among the arguments both for and against is the lack of correlation
      between objective values and the symptoms. OBJECTIVE: To evaluate the correlation
      between clinical data and apnea-hypopnoea index (AHI) in our work environment.
      MATERIAL AND METHODS: We compared the preoperative clinical symptoms and AHI
      statistically in 170 children with sleep-disordered breathing who underwent
      polysomnography. We also analysed the correlation to postoperative level, with a
      subgroup of 80 children who underwent adenotonsillectomy with 1 year of
      polysomnography follow-up. RESULTS: Before surgery, only the degree of tonsillar
      hypertrophy was statistically significant correlated with AHI. At post-operative
      follow-up, evidence of correlation between AHI and apnoea was observed: 38.1% of
      children improved in the group with persistence and 66.7% in the disease
      resolution group (P=.023). In addition, the correlations showed the level of
      improvement of snoring, as assessed by visual analogue scale. The mean was 5
      points lower in the persistent group and 6.1 lower in the disease resolution
      group (P=.047). CONCLUSION: Despite the limitations in the correlation between
      clinical data and polysomnography, especially in preoperative results,
      polysomnography remains the gold standard diagnostic tool. Efforts should be made
      to obtain objective parameters that provide higher levels of correlation.

PMID- 23141635
TI  - [Trisomy 21 and cancers].
AB  - Patients with trisomy 21, still called Down's syndrome (DS), present a particular
      tumoral profile compared to the general population with an increased incidence of
      leukaemia in the childhood and a low risk of solid cancer in the adulthood. DS
      children indeed present a 50-fold risk of developing a leukaemia compared to age
      matched non-trisomic children and most of them develop a specific myelodysplasic
      disorder called transient myelodysplasic disorder. In spite of the low incidence
      of solid tumors, some are very rare as breast cancer, nephroblastoma,
      neuroblastoma and medulloblastoma, whereas the others remain more frequent as
      retinoblastoma, lymphoma and gonadal and extragonadal germ cell tumours. In this
      review, we present possible mechanisms which can favour, or on the contrary
      repress the formation and progression of tumours in DS patients, which are
      related to gene effect dosage of oncogenes or tumour repressors on chromosome 21,
      tumour angiogenesis, apoptosis and epithelial cell-stroma interactions.

PMID- 23141634
TI  - Plasma membrane growth during the cell cycle: unsolved mysteries and recent
      progress.
AB  - Growth of the plasma membrane is as fundamental to cell reproduction as DNA
      replication, chromosome segregation and ribosome biogenesis, yet little is known
      about the underlying mechanisms. Membrane growth during the cell cycle requires
      mechanisms that control the initiation, location, and extent of membrane growth,
      as well as mechanisms that coordinate membrane growth with cell cycle
      progression. Recent experiments have established links between membrane growth
      and core cell cycle regulators. Further analysis of these links will yield
      insights into conserved and fundamental mechanisms of cell growth. A better
      understanding of the post-Golgi pathways by which membrane growth occurs will be
      essential for future progress.

PMID- 23141636
TI  - Generalization of treadmill-slip training to prevent a fall following a sudden
      (novel) slip in over-ground walking.
AB  - The purposes of the study were to determine (1) whether treadmill-slip training
      could reduce the likelihood of falls during a novel slip in over-ground walking,
      and (2) to what extent such (indirect) training would be comparable to (direct)
      over-ground-slip training. A treadmill-slip training group (Group A, n=17)
      initially experienced repeated perturbations on treadmill intended to simulate
      forward-slip in over-ground walking. Perturbation continued and its intensity
      reduced when necessary to ensure subjects' successful adaptation (i.e., when they
      could land their trailing foot ahead of the slipping foot in at least 3 of 5
      consecutive trials). They then experienced a novel slip during over-ground
      walking. Another 17 young adults in Group B experienced an identical novel slip
      that served as the controls. They then underwent more slip trials during over
      ground walking. Their 16th slip trial was analyzed to represent the over-ground
      slip training effect. Eight subjects (47%) in Group A fell upon their first
      treadmill slip, while all adapted successfully after a minimum of 15 slip trials.
      Upon the novel slip during over-ground walking, none of them fell in comparison
      to four subjects (23.5%) fell in Group B upon the same trial (p<0.05). Group A's
      control of stability, both proactive and reactive, was significantly better than
      that of Group B's on their first over-ground slip, while the level of improvement
      in the control of stability derived from indirect treadmill training was not as
      strong as that from direct over-ground-slip training, as demonstrated in Group
      B's 16th slip trial (p<0.001). These results clearly demonstrated the feasibility
      of fall reduction through treadmill-slip training.

PMID- 23141638
TI  - The ground reaction vector in walking passes always (almost) through the same
      point.

PMID- 23141637
TI  - Three-dimensional knee moments of ACL reconstructed and control subjects during
      gait, stair ascent, and stair descent.
AB  - Changes in knee mechanics following anterior cruciate ligament reconstruction
      (ACLR) have been implicated as a contributor to the development of premature
      osteoarthritis (OA). However, changes in ambulatory loading in this population
      have not been well documented. While the magnitude of the external knee moment
      vector is a major factor in loading at the knee, there is not a comprehensive
      understanding of the changes in the individual components of the vector following
      ACL reconstruction. The purpose of this study was to test for differences in the
      three components of the external knee moment during walking and stair locomotion
      between ACLR, contralateral and healthy control knees. Forty-five ACLR and 45
      healthy control subjects were tested during walking, stair ascent and descent.
      ACLR knees had a lower first peak adduction moment than contralateral knees
      during all three activities. Similarly, additional cases of significant
      differences between ACLR and contralateral knees consisted of lower peak moments
      for the ACLR than the contralateral knees. These differences were due to both
      ACLR and contralateral knees as the ACLR knees indicated lower and the
      contralateral knees greater peak moments compared to healthy control knees. The
      results suggest a compensatory change involving greater loading in the
      contralateral knee, perhaps due to lower loading of the ACLR knee. Further, lower
      knee moments of the ACLR knee suggest that increased joint loading may not be the
      initiating factor in the development of OA following ACL reconstruction; but
      rather previous described kinematic or biological changes might initiate the
      pathway to knee OA.

PMID- 23141639
TI  - The dominant microbial community associated with fermentation of Obushera
      (sorghum and millet beverages) determined by culture-dependent and culture
      independent methods.
AB  - Obushera includes four fermented cereal beverages from Uganda namely: Obutoko,
      Enturire, Ekitiribita and Obuteire, whose microbial diversity has not hitherto
      been fully investigated. Knowledge of the microbial diversity and dynamics in
      these products is crucial for understanding their safety and development of
      appropriate starter cultures for controlled industrial processing. Culture
      dependent and culture-independent techniques including denaturating gradient gel
      electrophoresis (DGGE) and mixed DNA sequencing of polymerase chain reaction
      (PCR) amplified ribosomal RNA genes were used to study the bacteria and yeast
      diversity of Obushera. The pH dropped from 6.0-4.6 to 3.5-4.0 within 1-2 days for
      Obutoko, Enturire and Obuteire whereas that of Ekitiribita decreased to 4.4 after
      4 days. Counts of lactic acid bacteria (LAB) increased from 5.0 to 11.0 log cfug(
      1) and yeasts increased from 3.4 to 7.1 log cfug(-1) while coliform counts
      decreased from 2.0 to <1 log cfug(-1) during four days of fermentation. LAB and
      yeast isolates were identified by rRNA gene sequence analysis. LAB isolates
      included: Enterococcus spp., Lactobacillus (Lb.) plantarum, Lb. fermentum, Lb.
      delbrueckii, Lactococcus lactis, Leuconostoc lactis, Streptococcus (S.)
      infantarius subsp. infantarius, Pediococcus pentosaceus and Weisella (W.)
      confusa. DGGE indicated predominance of S. gallolyticus, S. infantarius subsp.
      infantarius, Lb. fermentum, Lb. delbrueckii, W. confusa, Lb. reuteri,
      Fructobacillus spp., L. lactis and L. lactis. Yeast isolates included Clavispora
      lusitaniae, Cyberlindnera fabianii, Issatchenkia orientalis and Saccharomyces
      cerevisiae. DGGE indicated predominance of S. cerevisiae in Obutoko, Enturire and
      Obuteire and also detected Pichia spp. and I. orientalis in Obutoko. Obushera
      produced in the laboratory was initially dominated by Enterobacteriaceae and
      later by Lactococcus spp. Enterobacteriaceae and Bacillus spp. were also detected
      in Ekitiribita. Development of starters for Obushera may require combinations of
      LAB and S. cerevisiae for Obutoko, Enturire and Obuteire and LAB for Ekitiribita.

PMID- 23141640
TI  - Industrial disinfectants do not select for resistance in Listeria monocytogenes
      following long term exposure.
AB  - Listeria monocytogenes is a food-borne pathogen that can persist for years in
      food processing plants. It has been hypothesized that this could be due to the
      development of tolerance or resistance to the disinfectants used. The purpose of
      the present study was to determine whether biocide resistance or tolerance would
      evolve in L. monocytogenes under continued selection in three industrial
      disinfectants. L. monocytogenes EGD was exposed to Desinfect CL (hypochlorite)
      and Incimaxx DES (peracedic acid and hydrogen peroxide) for several hundred
      generations. This caused no increase in the minimal inhibitory concentration
      (MIC) to the disinfectants, whereas exposure to Triquart SUPER (quaternary
      ammonium compounds) caused a two- to four-fold increase in MIC. Exposure to
      gentamicin, which was used as a positive control, caused an 8 to 256-fold
      increase in MIC for several aminoglycosides. Despite the low level of tolerance,
      the populations adapted to Triquart SUPER were still sensitive to killing with
      this disinfectant at 0.0125%, which is much lower than in-use concentrations (1
      5%). Our data are in agreement with the fact that finding strains with high
      acquired resistance to disinfectants is rare, and that the disinfectants are
      still efficient for controlling microorganisms such as L. monocytogenes.

PMID- 23141641
TI  - Phenotypic and genotypic features of antibiotic resistance in Salmonella enterica
      isolated from chicken meat and chicken and quail carcasses.
AB  - One hundred and twenty-three Salmonella enterica isolated in Italy from chicken
      meat and carcasses and from quail carcasses were analyzed to determine their
      levels of antibiotic resistance using antibiograms (phenotypic method) and PCR
      amplification of antimicrobial resistance-associated genes (genotypic method).
      The isolates were screened for the ability to grow in the presence of antibiotics
      (ampicillin, gentamicin, sulfamethoxazole and tetracycline) and for the presence
      of the following genes: pse-1, ant (3")-Ia, qacEDeltaI and sul-1, tetA, tetB and
      tetG. The most frequently isolated serotypes in the sample set were S. Virchow
      (24.4%), S. Enteritidis (17.1%) and S. Typhimurium (15.4%). Of the isolates from
      chicken carcasses, 86.1% were resistant to tetracycline, while 30.5% of the
      identified isolates exhibited phenotypic multi-drug resistance to ampicillin,
      sulfamethoxazole and tetracycline; the multi-resistance pattern ant (3")-Ia/sul
      1/tetA+tetB was detected in 11.1% of the isolates. Of the isolates from quail
      carcasses, 89.2% exhibited resistance to sulfamethoxazole, and 24.3% displayed
      phenotypic multi-drug resistance to ampicillin, gentamicin, sulfamethoxazole and
      tetracycline; a complete genotypic profile (pse-1, ant (3")-Ia, qacEDeltaI and
      sul-1, tetA, tetB and tetG) was obtained for 27.0% of the isolates. Among these
      isolates, S. Typhimurium exhibited the genotypes pse-1/ant(3")-Ia/sul-1/tetG and
      pse-1/ant(3")-Ia/sul-1/tetA+tetG. Of the isolates from chicken meat, 60.0% were
      resistant to tetracycline, and 36.0% exhibited a multi-drug resistance to
      ampicillin, sulfamethoxazole and tetracycline; only one isolate, S. Enteritidis,
      contained the complete genotypic pattern pse-1/ant(3")-Ia/sul-1/tetG. The
      majority of the isolates displaying multi-drug resistance to the three
      antibiotics were isolated from chicken meat (40.0%).

PMID- 23141642
TI  - Prevalence and level of Listeria monocytogenes in ready-to-eat foods in Sweden
      2010.
AB  - An increasing trend in human listeriosis cases over the past five years (2005
      2009) in Sweden encouraged the authorities to examine the prevalence and levels
      of Listeria monocytogenes in ready-to-eat (RTE) foods in 2010. The combined
      results of two surveys are presented: the Swedish part of an EU-wide survey and a
      national survey. A total of 1590 samples covering three categories of RTE food
      able to support growth of L. monocytogenes: (i) soft and semi-soft cheeses (mould
      and smear-ripened); (ii) heat-treated meat products; and (iii) smoked and gravad
      fish, were collected at retail outlets and analysed at the end of shelf life. L.
      monocytogenes was detected in 0.4% of 525 cheese samples, 1.2% of 507 meat
      product samples and 12% of 558 fish samples. In the latter category, L.
      monocytogenes was found in 14% of both gravad and cold-smoked fish samples and in
      approximately 2% of hot-smoked fish samples. The percentage of cold-smoked or
      gravad fish testing positive for L. monocytogenes was significantly lower in
      samples processed in Sweden (8%) than in samples processed in other countries
      (45%). Levels of L. monocytogenes exceeding 100 cfu/g were found in one (0.2%) of
      the cheese samples and in three (0.5%) of the fish samples. The high prevalence
      of contaminated cold-smoked and gravad fish samples suggests that these products
      constitute the main problem. This has induced the development of a national
      strategy plan with the aim to halve the prevalence of L. monocytogenes in cold
      smoked and gravad fish at retail in Sweden by the end of year 2015.

PMID- 23141643
TI  - Mathematical modeling and numerical analysis of the growth of non-O157 Shiga
      toxin-producing Escherichia coli in spinach leaves.
AB  - This study was conducted to investigate the growth of non-O157 Shiga toxin
      producing Escherichia coli (STEC) in spinach leaves and to develop kinetic models
      to describe the bacterial growth. Six serogroups of non-O157 STEC, including O26,
      O45, O103, O111, O121, and O145, were used in the growth studies conducted
      isothermally at 4, 8, 15, 20, 25, 30, and 35  degrees C. Both STEC and background
      microflora were enumerated to develop kinetic models. Growth of STEC in spinach
      leaves was observed at elevated temperatures (15-35  degrees C), but not at 4 and
      8  degrees C. This study considered the dynamic interactions between the STEC
      cells and the background microflora. A modified Lotka-Volterra and logistic
      equation was used to simulate the bacterial growth. In combination with an
      unconstrained optimization procedure, the differential growth equations were
      solved numerically to evaluate the dynamic interactions between the STEC cells
      and the background microflora, and to determine the kinetic parameters by fitting
      each growth curve to the growth equations. A close agreement between the
      experimental growth curves and the numerical analysis results was obtained. The
      analytical results showed that the growth of STEC in spinach leaves was
      unhindered when the population was low, but the growth was suppressed by the
      background microflora as the STEC population approached the maximum population
      density. The effect of temperature on the growth of both STEC and background
      microflora was also evaluated. Secondary models, evaluating the effect of
      temperature on growth rates, were also developed. The estimated apparent minimum
      growth temperature for STEC was 11  degrees C in commercial spinach leaves. The
      methodology and results of this study can be used to examine the dynamic
      interactions and growth between different bacteria in foods, and to conduct risk
      assessments of STEC in spinach leaves.

PMID- 23141644
TI  - Yeasts in table olive processing: desirable or spoilage microorganisms?
AB  - Yeasts are unicellular eukaryotic microorganisms isolated from many foods, and
      are commonly found in table olive processing where they can play a double role.
      On one hand, these microorganisms can produce spoilage of fruits due to the
      production of bad odours and flavours, the accumulation of CO(2) leading to
      swollen containers, the clouding of brines, the softening of fruits and the
      degradation of lactic acid, which is especially harmful during table olive
      storage and packaging. But on the other hand, fortunately, yeasts also possess
      desirable biochemical activities (lipase, esterase, beta-glucosidase, catalase,
      production of killer factors, etc.) with important technological applications in
      this fermented vegetable. Recently, the probiotic potential of olive yeasts has
      begun to be evaluated because many species are able to resist the passage through
      the gastrointestinal tract and show beneficial effects on the host. In this way,
      yeasts may improve consumers' health by decreasing cholesterol levels, inhibiting
      pathogens, degrading non assimilated compounds, producing antioxidants and
      vitamins, adhering to intestinal cells or by maintaining epithelial barrier
      integrity. Many yeast species, usually also found in table olive processing, such
      as Wicherhamomyces anomalus, Saccharomyces cerevisiae, Pichia membranifaciens and
      Kluyveromyces lactis, have been reported to exhibit some of these properties.
      Thus, the selection of the most appropriate strains to be used as starters, alone
      or in combination with lactic acid bacteria, is a promising research line to
      develop in a near future which might improve the added value of the
      commercialized product.

PMID- 23141645
TI  - Influences of heating temperature, pH, and soluble solids on the decimal
      reduction times of acid-adapted and non-adapted Escherichia coli O157:H7 (HCIPH
      96055) in a defined liquid heating medium.
AB  - The study characterized the influences of various combinations of process and
      product parameters namely, heating temperature (53, 55, 57.5, 60, 62  degrees C),
      pH (2.0, 3.0, 4.5, 6.0, 7.0), and soluble solids (SS) (1.4, 15, 35, 55, 69
      degrees Brix) on the thermal inactivation of non-adapted and acid-adapted E. coli
      O157:H7 (HCIPH 96055) in a defined liquid heating medium (LHM). Acid adaptation
      was conducted by propagating cells in a gradually acidifying nutrient broth
      medium, supplemented with 1% glucose. The D values of non-adapted cells ranged
      from 1.43 s (0.02 min) to 304.89 s (5.08 min). Acid-adapted cells had D values
      that ranged from 1.33 s (0.02 min) to 2628.57 s (43.81 min). Adaptation did not
      always result in more resistant cells as indicated by the Log (D(adapted)/D(non
      adapted)) values calculated in all combinations tested, with values ranging from 
      1.10 to 1.40. The linear effects of temperature and pH, and the joint effects of
      pH and SS significantly influenced the thermal resistance of non-adapted cells.
      Only the linear and quadratic effects of both pH and SS significantly influenced
      the D values of acid-adapted cells. Generally, the D values of acid-adapted cells
      decreased at SS greater than 55  degrees Brix, suggesting the possible
      cancelation of thermal cross protection by acid habituation at such SS levels.
      The relatively wide ranges of LHM pH and SS values tested in the study allowed
      for better examination of the effects of these factors on the thermal death of
      the pathogen. The results established in this work may be used in the evaluation,
      control and improvement of safety of juice products; and of other liquid foods
      with physicochemical properties that fall within the ranges tested in this work.

PMID- 23141646
TI  - Adhesion and splash dispersal of Salmonella enterica Typhimurium on tomato
      leaflets: effects of rdar morphotype and trichome density.
AB  - Salmonella enterica strains with rdar (red dry and rough) and saw (smooth and
      white) morphotypes have previously been associated with tomato outbreaks but the
      dispersal mechanisms of these morphotypes are still poorly understood. In this
      study, Salmonella adhesion was distinguished from attachment by comparing
      different contact periods. Initial adhesion of rdar and saw morphotypes of
      Salmonella was compared in relation to tomato plants with different leaf trichome
      densities. Trichome densities were increased or reduced by treatment with
      jasmonic or salicylic acid, respectively. The overall effect of Salmonella
      morphotype and trichome density on splash dispersal was assessed in a rain
      simulator and correlated to cell hydrophobicity and initial adhesion. The
      presence of the rdar morphotype increased initial adhesion at high trichome
      densities but not at low trichome densities. Attachment of the rdar strain
      occurred after 30s contact time regardless of trichome density. Splash dispersal
      was slightly further for the saw morphotype than the rdar morphotype of S.
      enterica at all trichome densities. Salmonella cells of both morphotypes survived
      significantly better on the surface of high trichome density leaflets.

PMID- 23141647
TI  - Effect of O(2)-CO(2) enriched atmospheres on microbiological growth and volatile
      metabolite production in packaged cooked peeled gray shrimp (Crangon crangon).
AB  - This study evaluated the effect of modified atmospheres (MAs) with different O(2)
      concentrations on microbial growth and volatile metabolite production in gray
      shrimp (Crangon crangon) during storage at 4  degrees C. Eight MAs were evaluated
      in total. Four of the MAs evaluated were without CO(2): 0/0/100, 0/10/90,
      0/30/70, 0/50/50 (% CO(2)/O(2)/N(2)) whilst the other four MAs all contained 50%
      CO(2): 50/0/50, 50/10/40, 50/30/20, 50/50/0 (% CO(2)/O(2)/N(2)). Volatile
      spoilage metabolites were identified by thermal desorption GC-MS and quantified
      during storage by selective ion flow tube mass spectrometry (SIFT-MS). In
      comparison to microbial growth observed with an atmosphere of 100% N(2),
      microbial growth was stimulated by the addition of O(2) in the MAP in the absence
      of CO(2.) Under these conditions the total psychrotrophic counts exceeded 7 log
      cfug(-1) after just 3 days of storage. However, in the presence of 50% CO(2) the
      total psychrotrophic count exceeded 7 log cfug(-1) after 5 days of storage. The
      combination of 50% CO(2) and 50% O(2) significantly inhibited microbial growth.
      For this MA condition, a diminishing effect on the production of metabolites was
      also observed, especially for amines and sulfur compounds, which constituted the
      major fraction of components causing the offensive odor.

PMID- 23141648
TI  - Detection of virulence-associated genes and epidemic clone markers in Listeria
      monocytogenes isolates from PDO Gorgonzola cheese.
AB  - Fifty-three Listeria monocytogenes isolates obtained from Gorgonzola cheese and
      previously characterized with biochemical typing, serotyping and pulsed field gel
      electrophoresis (PFGE), were analyzed in this study. Seven virulence-associated
      genes were selected (actA, inlC, inlJ, plcA, prfA, hlyA and iap) and their
      presence was investigated using PCR. All virulence-associated genes were detected
      in 51 isolates. One isolate did not show amplification of the inlC gene and one
      other isolate, previously mis-identified as L. monocytogenes probably due to
      atypical phenotypes, resulted negative by PCR for all virulence genes and was
      identified as Listeria innocua by 16S rRNA gene sequencing analysis. A multiplex
      PCR assay was used to evaluate the presence of markers specific for epidemic
      clones (ECs) of L. monocytogenes. The marker specific for the recently identified
      epidemic clone V (ECV) was detected in 38 of 43 (88%) of serotype 1/2a isolates.
      These findings suggest that Gorgonzola cheese can represent a significant source
      of L. monocytogenes and potential health risk for listeriosis as almost all
      isolates (94%) could be potentially virulent and that 38 (~72%) were presumptive
      positive ECV. PCR screening for both virulence-associated genes and EC markers
      may be useful for rapidly evaluating the epidemic potential and public health
      risk posed by L. monocytogenes in PDO Gorgonzola cheese and other dairy products.

PMID- 23141649
TI  - Effect of storage conditions (relative humidity, duration, and temperature) on
      the germination time of Aspergillus carbonarius and Penicillium chrysogenum.
AB  - Fungal conidia are disseminated, often in the air, for a certain period of time,
      prior to contaminating food products. The objective of this study was to examine
      the effects of the relative humidity, RH (%), time (day), and temperature (
      degrees C) during this period of time, called "storage", on the germination time,
      tau (h), of Aspergillus carbonarius and Penicillium chrysogenum. A Doehlert
      design was used in the range, 20-100% RH, 2-28 days, and 5-25  degrees C. As
      compared to un-stored conidia, the germination time of conidia stored at 60% RH,
      15 days, 5  degrees C was increased by 23 and 28%, for A. carbonarius and P.
      chrysogenum, respectively. Stored conidia exhibited a minimum tau value at 60%
      RH, and 100% RH for A. carbonarius and P. chrysogenum, respectively. For these
      species, tau was minimum for 2 days of storage. The effect of temperature was RH
      dependent for A. carbonarius. The germination time of stored conidia was clearly
      greater than that of fresh conidia obtained in the laboratory. This result should
      be taken into account to determine the mould free shelf-life of food products.

PMID- 23141650
TI  - In search of perfect frozen sections.

PMID- 23141651
TI  - [Oral digital techniques and materials].

PMID- 23141652
TI  - [Research and application of robot technology in surgical auxiliary operation].

PMID- 23141653
TI  - [Research and application of a haptics-based virtual-reality training system for
      craniomaxillofacial surgery].

PMID- 23141654
TI  - [Digital surgery technique to accurately reconstruct orbital fracture].

PMID- 23141656
TI  - [Digital design technique in the reconstruction of traumatic craniomaxillofcial
      deformities].

PMID- 23141655
TI  - [Application of digital surgical techniques on correction of dento-maxillofacial
      deformities].

PMID- 23141657
TI  - [Digital surgery techniques applied in mandibular reconstruction].

PMID- 23141658
TI  - [A micro-computed tomographic analysis of the apical anatomy of permanent three
      rooted mandibular first molars].
AB  - OBJECTIVE: To investigate the anatomic features of the root apexes of permanent
      three-rooted mandibular first molars. METHODS: A total of 122 permanent
      mandibular first molars of Han Chinese patients were collected. Twenty three
      rooted and 25 two-rooted molars were scanned by micro-CT and then reconstructed
      three-dimensionally. The apical anatomy of the tooth models were analyzed in
      software Mimics 10.01. The long and short diameters of the apical constriction
      (AC), the distances between AC, apical foramen (AF) and apex were measured. One
      way ANOVA and LSD-t tests were used to compare the groups in relation to AC
      diameter and the distances between the AC, AF and apex. RESULTS: The AF of the
      mesiobuccal (MB) canals most frequently presented at the distal side of the apex
      (10 cases in three-rooted and 6 cases in two-rooted group), and of the
      mesiolingual (ML) canals, most often at the lingual side (8 cases in each group).
      The AF of the distobuccal (DB) roots were frequently located at the distolingual
      (DL) side (10 cases), and those of the DL roots and distal canals of two-rooted
      molars were most often at the buccal (7 cases) and distal (11 cases) sides,
      respectively. The percentage of the "classical" singular AC was 53% (80/151). The
      average long(D) and short(d) diameters of the AC of the DB canals were (0.32 +/-
      0.09) mm and (0.25 +/- 0.05) mm, respectively, significantly larger than the DL
      canals [D = (0.27 +/- 0.08) mm, d = (0.22 +/- 0.06) mm, P < 0.05] and the ML
      canals [D = (0.24 +/- 0.06) mm, d = (0.19 +/- 0.06) mm, P < 0.01). In three
      rooted group, the mean distances between AC and AF, AF and apex, and AC and apex
      were (0.67 +/- 0.32), (0.49 +/- 0.28) and (1.01 +/- 0.34) mm, respectively.
      CONCLUSIONS: The AF of three-rooted mandibular molars frequently deviate from the
      root apex, and the AC of the DB canal is wider than those of the other canals.
      The mean distances between AC, AF and the apex suggest that root canal therapy
      should terminate at 1 to 1.5 mm short of the radiographic apex.

PMID- 23141659
TI  - [Femtosecond pulsed laser ablation of dental hard tissues with numerical control:
      a roughness and morphology study].
AB  - OBJECTIVE: To establish the femtosecond laser experimental platform in vitro for
      numerical controlled cavity preparation, and to evaluate the roughness
      quantitatively and observe the microscopic morphology of the cutting surface.
      METHODS: Enamel and dentin planes were prepared on human third molars. A
      universal motion controller was used to control the samples to do rectangle wave
      motion perpendicular to the incident direction of the laser at focus. The surface
      roughness was observed with confocal laser scanning microscope. RESULTS: Precise
      ablation of the dental hard tissues can be achieved with the established
      femtosecond laser numerical control platform. For enamel, the surface roughness
      of the cavity inside laser scanning line was 7.173 um at the bottom and 2.675 um
      on the wall of the cavity. The surface roughness of the cavity between laser
      scanning lines was 13.667 um at the bottom and 33.927 um on the wall. For dentin,
      the surface roughness of the cavity bottom was 51.182 um and 25.629 um for the
      wall. Scanning electron microscope images showed no micro-cracks or carbonization
      on enamel, while carbonization, cracks and a small amount of crystalline
      particles were observed on dentin. CONCLUSIONS: Precise tooth preparation can be
      achieved with femtosecond laser numerical control flatform. The surface roughness
      of cavity wall was less than that of the bottom and can meet the clinical needs.
      Suitable femtosecond laser output power should be set for different cutting
      objects, otherwise it may result in tissue damages.

PMID- 23141660
TI  - [Comparative studies of casein phosphopeptide-amorphous calcium phosphate and
      fluoride products in inhibiting enamel demineralization].
AB  - OBJECTIVE: To evaluate casein phosphopeptide-amorphous calcium phosphate (CPP
      ACP) and several fluoride products in inhibiting enamel demineralization.
      METHODS: Seventy healthy premolars extracted before orthodontic treatment were
      divided into seven groups (A: CPP-ACP; B: CPP-ACP + fluoride mouth rinses; C:
      fluoride mouth rinses; D: fluoride glass ionomer protection; E: fluoride resin
      binder; F: fluoride varnish; G: control group). There were ten samples in each
      group. The teeth were dipped into an artificial caries solution ten minutes at a
      time, then applied separately with CPP-ACP, CPP-ACP + fluoride mouth rinses,
      fluoride mouth rinses, fluoride glass ionomer protection, fluoride resin binder
      and fluoride varnish on labial enamel. The samples were dipped into an artificial
      saliva solution (37 degrees C). Then all samples were examined with atomic force
      microscope (AFM) at the end of first, second and third monthes. RESULTS: At the
      end of the first month, surface roughness in group D [(114 +/- 1) nm] was
      significantly lower than that in group G[(172 +/- 9) nm]. At the end of the
      second month and the third month, significant difference was found in surface
      roughness between group G and the rest of groups (P < 0.05); between group B and
      the rest of groups; and between group C and groups (D, E and F). CONCLUSIONS: CPP
      ACP and fluoride could both inhibit enamel demineralization in vitro. Solid
      fluoride (groups D, E and F) had better results than liquid fluoride (group C).

PMID- 23141661
TI  - [Influence of receptor activity modifying protein 1 overexpression on enhancing
      effect of calcitonin gene-related peptide on MG-63 cells proliferation].
AB  - OBJECTIVE: To investigate the influnce of receptor activity modifying protein
      1(RAMP-1) overexpression on enhancing effect of calcitonin gene-related peptide
      on MG-63 cells proliferation. METHODS: Cultured MG-63 osteoblasts in exponential
      phase of growth were randomly divided into three groups: RAMP-1 overexpression
      group, empty vector control group and negative control group. RAMP-1 eukaryotic
      expression vector was constructed and stably transfected into MG-63 cells.
      Realtime-polymerase chain reaction, Western blotting and immunofluroescence were
      used respectively to detect the expression of calcitonin receptor-like receptor
      (CRLR) in the cells and its distribution on cell membrane. The status of
      proliferation was detected respectively at 0, 24, 48, 72, 96 h by cell counting
      kit-8 (CCK-8) and cells were collected to analyze their cycle respectively at 0,
      8, 16, 24 h by flow cytometry. RESULTS: CRLR protein and mRNA expression levels
      of MG-63 cells in RAMP-1 overexpression group were significantly higher than the
      other two groups (P < 0.05). The A value of RAMP-1 overexpression group at 24,
      48, 72, 96 h were 0.628 +/- 0.175, 0.896 +/- 0.592, 1.055 +/- 0.004, 1.179 +/-
      0.618, respectively, which were significantly higher than that of the other two
      groups (P < 0.05). The difference was most pronounced at 72 h. S-phase fraction
      of RAMP-1 overexpression group was (1.25 +/- 0.13)%, (68.79 +/- 0.56)%, (64.49 +/
      1.59)%, (57.82 +/- 0.75)%, respectively, which were significantly higher than
      the other two groups (P < 0.05). The difference was most pronounced at 8 h.
      CONCLUSIONS: RAMP-1 overexpression can promote CRLR distribution on MG-63 cell
      membrane and enhance CGRP's promotion effect on MG-63 cell proliferation.

PMID- 23141662
TI  - [Application of integrated digital maxillodental model in computer aided design
      of individualized lingual brackets].
AB  - OBJECTIVE: To create an integrated digital maxillodental model and to apply it in
      computer aided design (CAD) of individualized lingual brackets in order to align
      both crowns and roots without fenestration and dehiscence. METHODS: Cone-beam
      computerized tomography (CBCT)-based maxillodental model and laser-scanned dental
      model were integrated by auto registration in 10 patients with malocclusions. The
      registration error was calculated automatically. Three observers tested the
      method independently. The inter-observer difference was investigated. An
      integrated model was selected randomly and the setup was created with roots and
      jaws in good relationship without fenestration and dehiscence. The individualized
      lingual brackets were designed by CAD on the setup. RESULTS: No significant
      difference was found in inter observers (P > 0.05). The registration errors of
      maxilla and mandible were (0.144 +/- 0.020) mm and (0.141 +/- 0.022) mm,
      respectively. The digital individualized lingual brackets based on the virtual
      treatment in integrated digital maxillodental model were produced. CONCLUSIONS:
      An integrated digital maxillodental model was created in good accuracy. By
      applying the integrated model, individualized lingual brackets were designed.

PMID- 23141663
TI  - [Developing an easy-operating system for testing mechanical properties of
      thermoplastic materials in thermostatic waterbath].

PMID- 23141664
TI  - [Progress on management of ectopic eruption of first permanent molars for
      children].

PMID- 23141665
TI  - [Ultraviolet radiation can improve the biological activity of titanium surface].

PMID- 23141666
TI  - Application of cavitation promoting surfaces in management of acute ischemic
      stroke.
AB  - High frequency, low intensity ultrasound has the potential to accelerate the
      clearance of thrombotic occlusion in the absence of cavitation. At high frequency
      ultrasound, high acoustic pressures, >5.2MPa, are required to generate cavitation
      in thrombus. The focus of this study was to reduce the cavitation threshold by
      applying materials with appropriate nucleation sites at the transducer-thrombus
      boundary to further augment sonothrombolysis. Heterogeneous and homogenous
      nucleation sites were generated on the outer surface of a polyimide tube (PI)
      using microfringed (MPI) and laser induced (LPI) microcavities. The cavitation
      threshold of these materials was determined using a passive cavitation detection
      system. Furthermore, the biological impact of both materials was investigated in
      vitro. The results revealed that both MPI and LPI have the potential to induce
      cavitation at acoustic pressure levels as low as 2.3MPa. In the presence of
      cavitation, thrombolysis rate could be enhanced by up to two times without any
      evidence of hemolysis that is generally associated with cavitation activities in
      blood. A prototype ultrasonic catheter operating at 1.7MHz frequency and acoustic
      pressure of 2.3MPa with either of MPI or LPI could be considered as a viable
      option for treatment of acute ischemic stroke.

PMID- 23141667
TI  - Fast simulation of non-linear pulsed ultrasound fields using an angular spectrum
      approach.
AB  - A fast non-linear pulsed ultrasound field simulation is presented. It is
      implemented based on an angular spectrum approach (ASA), which analytically
      solves the non-linear wave equation. The ASA solution to the Westervelt equation
      is derived in detail. The calculation speed is significantly increased compared
      to a numerical solution using an operator splitting method (OSM). The ASA has
      been modified and extended to pulsed non-linear ultrasound fields in combination
      with Field II, where any array transducer with arbitrary geometry, excitation,
      focusing and apodization can be simulated. The accuracy of the non-linear ASA is
      compared to the non-linear simulation program - Abersim, which is a numerical
      solution to the Burgers equation based on the OSM. Simulations are performed for
      a linear array transducer with 64 active elements, focus at 40mm, and excitation
      by a 2-cycle sine wave with a center frequency of 5MHz. The speed is increased
      approximately by a factor of 140 and the calculation time is 12min with a
      standard PC, when simulating the second harmonic pulse at the focal point. For
      the second harmonic point spread function the full width error is 1.5% at -6dB
      and 6.4% at -12dB compared to Abersim.

PMID- 23141668
TI  - Cigarette smoking and subsequent risk of suicidal ideation among National Guard
      Soldiers.
AB  - BACKGROUND: Suicide rates are alarmingly high among military personnel, and
      particularly Army National Guard soldiers. Smoking is also disproportionately
      common in the military. In this study, we intend to investigate the relationship
      between cigarette smoking and suicidal ideation among a representative sample of
      national guard soldiers. METHODS: A representative sample of Ohio Army National
      Guard soldiers were followed prospectively and information was gathered on
      smoking, suicidal ideation and depression at baseline and one year later.
      RESULTS: Smoking at baseline was associated with significantly increased
      likelihood of suicidal ideation at follow-up (OR=2.0 (1.3, 3.2)). This
      association persisted after adjusting for demographics and history of depression
      at baseline, but was no longer statistically significant after adjusting for
      depression at follow-up. LIMITATIONS: Measurement of smoking was somewhat
      limited. CONCLUSIONS: Army National Guard soldiers who smoke have a greater risk
      of subsequent suicidal ideation. Depression concurrent with suicidal ideation
      appears to explain this relationship. If these results are replicated, screening
      of soldiers who smoke may be recommended as a proactive step towards mitigating
      the high risk of suicide in military personnel.

PMID- 23141669
TI  - Structural brain abnormalities in women with subclinical depression, as revealed
      by voxel-based morphometry and diffusion tensor imaging.
AB  - BACKGROUND: Brain structural changes accompany major depressive disorder, but
      whether subclinical depression is accompanied by similar changes in brain volume
      and white matter integrity is unknown. By using voxel-based morphometry (VBM) of
      the gray matter and tract-specific analysis based on diffusion tensor imaging
      (DTI) of the white matter, we explored the extent to which abnormalities could be
      identified in specific brain structures of healthy adults with subclinical
      depression. METHODS: The subjects were 21 community-dwelling adults with
      subclinical depression, as measured by their Center for Epidemiologic Studies
      Depression Scale (CES-D) scores. They were not demented and had no neurological
      or psychiatric history. We collected brain magnetic resonance images of the
      patients and of 21 matched control subjects, and we used VBM to analyze the
      differences in regional gray matter volume between the two groups. Moreover, we
      examined the white matter integrity by using tract-specific analysis based on the
      gray matter volume changes revealed by VBM. RESULTS: VBM revealed that the
      volumes of both anterior cingulate gyri and the right rectal gyrus were smaller
      in subclinically depressed women than in control women. Calculation of DTI
      measures in the anterior cingulum bundle revealed a positive correlation between
      CES-D scale score and radial diffusivity in the right anterior cingulum in
      subclinically depressed women. LIMITATIONS: The small sample size limits the
      stability of the reported findings. CONCLUSIONS: Gray matter volume reduction and
      white matter integrity change in specific frontal brain regions may be associated
      with depressive symptoms in women, even at a subclinical level.

PMID- 23141670
TI  - Complex trauma and intimate relationships: the impact of shame, guilt and
      dissociation.
AB  - BACKGROUND: This study examined dissociation, shame, guilt and intimate
      relationship difficulties in those with chronic and complex PTSD. Little is known
      about how these symptom clusters interplay within the complex PTSD constellation.
      Dissociation was examined as a principle organizing construct within complex
      PTSD. In addition, the impact of shame, guilt and dissociation on relationship
      difficulties was explored. METHODS: Sixty five treatment-receiving adults
      attending a Northern Irish service for conflict-related trauma were assessed on
      measures of dissociation, state and trait shame, behavioral responses to shame,
      state and trait guilt, complex PTSD symptom severity and relationship
      difficulties. RESULTS: Ninety five percent (n=62) of participants scored above
      cut-off for complex PTSD. Those with clinical levels of dissociation (n=27) were
      significantly higher on complex PTSD symptom severity, state and trait shame,
      state guilt, withdrawal in response to shame and relationship preoccupation than
      subclinical dissociators (n=38). Dissociation and state and trait shame predicted
      complex PTSD. Fear of relationships was predicted by dissociation, complex PTSD
      and avoidance in response to shame, while complex PTSD predicted relationship
      anxiety and relationship depression. LIMITATIONS: The study was limited to a
      relatively homogeneous sample of individuals with chronic and complex PTSD drawn
      from a single service. CONCLUSIONS: Complex PTSD has significant consequences for
      intimate relationships, and dissociation makes an independent contribution to
      these difficulties. Dissociation also has an organizing effect on complex PTSD
      symptoms.

PMID- 23141671
TI  - Cell signaling and gene regulation.

PMID- 23141672
TI  - Effects of shade on plant growth and flower quality in the herbaceous peony
      (Paeonia lactiflora Pall.).
AB  - Herbaceous peony (Paeonia lactiflora Pall.) is an important ornamental plant used
      in urban green spaces, but little is known about whether it can grow in a shaded
      environment or understory. In this study, effects of shade on plant growth and
      flower quality in the herbaceous peony were investigated. The results showed that
      P. lactiflora morphology parameters, including plant height, leaf number, stem
      diameter, branch number, node number and plant crown width, were higher in plants
      grown with sun exposure compared to those grown in shade; however, opposite
      trends were observed for the top and middle leaf areas of the plant. Compared
      with sun exposure, shade decreased P. lactiflora photosynthetic capacity, light
      saturation point (LSP) and light compensation point (LCP) and increased the
      apparent quantum yield (AQY), mainly due to declined stomatal conduction (Gs).
      These decreases caused the soluble sugar, soluble protein and malondialdehyde
      (MDA) contents to decline, which led to delayed initial flowering date, prolonged
      flowering time, reduced flower fresh weight, increased flower diameter and faded
      flower color. Through cloning and expression analysis of anthocyanin biosynthetic
      genes, we determined that the fading of flower color was the result of reduced
      anthocyanin content, which was caused by the combined activity of anthocyanin
      biosynthesis genes and, in particular, of the upstream phenylalanine ammonialyase
      gene (PlPAL) and chalcone synthase gene (PlCHS). These results could provide us
      with a theoretical basis for further application of P. lactiflora in the greening
      of urban spaces and an understanding of the mechanisms behind the changes induced
      by shade.

PMID- 23141673
TI  - Transcriptomic analysis of oxylipin biosynthesis genes and chemical profiling
      reveal an early induction of jasmonates in chickpea roots under drought stress.
AB  - Drought is one of the major constraints in subtropical agriculture. Therefore
      improving water stress tolerance is of great importance to breed for drought
      tolerance in future. The first plant organ sensing dehydration is the root. Aim
      of the present work was to clarify the potential impact of the phyto-oxylipins
      pathway on drought tolerance of chickpea (Cicer arietinum), the third important
      legume crop worldwide. Therefore, we measured the expression of key genes
      involved in oxylipins metabolism by qPCR on samples from stressed and non
      stressed roots of a drought-tolerant and a drought-sensitive chickpea variety
      using commercially available TaqMan assays. We demonstrate that the drought
      tolerant variety reacts to drought with sustained and earlier activation of a
      specific lipoxygenase (Mt-LOX 1) gene, two hydroperoxide lyases (Mt-HPL 1 and Mt
      HPL 2), an allene oxide synthase (Mt-AOS), and an oxo-phytodienoate reductase (Mt
      OPR). We further show that gene over-expression positively correlates with the
      levels of major oxylipin metabolites from the AOS branch of the pathway, which
      finally leads to the synthesis of jasmonates. Higher levels of jasmonic acid
      (JA), its precursor 12-oxophytodienoic acid (OPDA) and the active form JA
      isoleucine (JA-Ile) were especially detected in the root tissues of the tolerant
      variety, prompting us to assume a role of jasmonates in the early signalling of
      drought stress in chickpea and its involvement in the tolerance mechanism of the
      drought-tolerant variety.

PMID- 23141674
TI  - An in vitro phantom study on the influence of tear size and configuration on the
      hemodynamics of the lumina in chronic type B aortic dissections.
AB  - OBJECTIVE: Management and follow-up of chronic aortic dissections continue to be
      a clinical challenge due to progressive dilatation and subsequent rupture. To
      predict complications, guidelines suggest follow-up of aortic diameter. However,
      dilatation is triggered by hemodynamic parameters (pressures/wall shear stresses)
      and geometry of false (FL) and true lumen (TL), information not captured by
      diameter alone. Therefore, we aimed at better understanding the influence of
      dissection anatomy on TL and FL hemodynamics. METHODS: In vitro studies were
      performed using pulsatile flow in realistic dissected latex/silicone geometries
      with varying tear number, size, and location. We assessed three different
      conformations: (1) proximal tear only; (2) distal tear only; (3) both proximal
      and distal tears. All possible combinations (n = 8) of small (10% of aortic
      diameter) and large (25% of aortic diameter) tears were considered. Pressure,
      velocity, and flow patterns were analyzed within the lumina (at proximal and
      distal sections) and at the tears. We also computed the FL mean pressure index
      (FPI(mean)%) as a percentage of the TL mean pressure, to compare pressures among
      models. RESULTS: The presence of large tears equalized FL/TL pressures compared
      with models with only small tears (proximal FPI(mean)% 99.85 +/- 0.45 vs 92.73 +/
      3.63; distal FPI(mean)% 99.51 +/- 0.80 vs 96.35 +/- 1.96; P < .001). Thus, large
      tears resulted in slower velocities through the tears (systolic velocity <180
      cm/s) and complex flows within the FL, whereas small tears resulted in lower FL
      pressures, higher tear velocities (systolic velocity >290 cm/s), and a well
      defined flow. Additionally, both proximal and distal tears act as entry and exit.
      During systole, flow enters the FL through all tears simultaneously, while during
      diastole, flow leaves through all communications. Flow through the FL, from
      proximal to distal tears or vice versa, is minimal. CONCLUSIONS: Our results
      suggest that FL hemodynamics heavily depends on cumulative tear size, and thus,
      it is an important parameter to take into account when clinically assessing
      chronic aortic dissections.

PMID- 23141675
TI  - Reintervention for distal stent graft-induced new entry after endovascular repair
      with a stainless steel-based device in aortic dissection.
AB  - OBJECTIVE: Stent graft-induced new entry (SINE) has been increasingly observed
      after thoracic endovascular aortic repair (TEVAR) for aortic dissection. We
      investigated the mechanism of late distal SINE, prevention strategies, proper
      size selection of the stent graft, and implantation sequence. METHODS: From
      November 2006 to May 2011, 99 patients with aortic dissection underwent TEVAR
      with Zenith TX2 stent grafts (Cook, Bloomington, Ind) at our center. Among them,
      27 distal SINEs were recognized. Eight of these patients with complicated distal
      SINE required intervention with new distal endografts, and all were enrolled for
      further analysis. RESULTS: Eight of the 27 patients with distal SINE underwent a
      secondary endograft procedure from February 2011 to July 2011. All were
      successfully treated without any complications or deaths. A high taper ratio
      (35%+/-11%) and excessive oversizing of the true lumen area at the distal stent
      level (293%+/-76%) were noted among these patients. CONCLUSIONS: The incidence of
      distal SINE seemed to be high; however, there were also low rates of death and
      complications after TEVAR for aortic dissection using stainless steel-based stent
      grafts. Complicated distal SINE can successfully be resolved by distal endograft
      implantation. Excessive oversizing of the distal stent graft, as measured by the
      true lumen area, may be a significant factor causing delayed distal SINE. Precise
      size selection is crucial for the distal end of the stent, especially for high
      taper ratio dissection pathology in which the implantation sequence of a distal
      small-sized stent graft first might be considered to prevent future distal SINE.

PMID- 23141677
TI  - Endovascular treatment of stenoses in a pediatric patient with incomplete aortic
      duplication, mesenteric ischemia, and renovascular hypertension.
AB  - Variations in abdominal aortic anatomy may have significant implications in
      various surgical procedures. We report here a pediatric patient with symptoms of
      chronic mesenteric ischemia, labile hypertension, and lower extremity
      claudication. Angiography revealed a partially duplicated aorta with the anterior
      aorta containing the splanchnic and renal arteries and the posterior segment
      perfusing the lower extremities. She was successfully treated with balloon
      angioplasty of two focal stenoses and is normotensive without abdominal symptoms
      at 1-year follow-up. To our knowledge, this is the first report of a successful
      endovascular intervention in a partially duplicated aorta.

PMID- 23141676
TI  - Hospital morbidity rankings and complication severity in vascular surgery.
AB  - INTRODUCTION: The American College of Surgeons National Surgical Quality
      Improvement Program ranks hospitals according to risk-adjusted rates of
      postoperative complications. However, this approach does not consider the
      severity or number of complications that occurred. We sought to determine whether
      incorporating this information would alter hospital rankings. METHODS: The study
      examined data for the 39,519 patients who underwent major vascular surgery in 206
      National Surgical Quality Improvement Program hospitals during 2008 to 2009. We
      categorized postoperative complications as minor or severe and evaluated the
      extent to which minor and severe complications increased a patient's risk of
      death and prolonged length of stay. We then ranked hospitals on two alternative
      approaches that included severity or number of complications. We determined the
      effect of these alternative methods by assessing the proportion of hospitals that
      moved out of the top and bottom 20% of hospitals compared with standard rankings.
      RESULTS: Compared with patients with minor complications, patients with severe
      complications had a higher mortality rate (16.2% vs 3.6%; P<.001) and prolonged
      length of stay (66.7% vs 53.3%; P<.001). Patients with two or more complications
      also had a higher mortality rate (23.7% vs 6.0%; P<.001) and prolonged length of
      stay (77.0% vs 50.1%; P<.001) than patients with only one complication. Compared
      with the current approach for assessing morbidity, ranking hospitals by severe
      complications resulted in 12 hospitals (29%) moving out of the top 20% and 10
      hospitals (24%) moving out of the bottom 20%. A similar degree of
      reclassification was found when the current rankings were compared with an
      alternative approach that considered the number of different complications.
      CONCLUSIONS: Although the severity and number of postoperative complications
      affect mortality and length of stay, and subsequently, hospital rankings,
      existing measurement systems do not take this into account. Quality measurement
      platforms should consider weighting complications according to severity and
      number.

PMID- 23141678
TI  - An outcome analysis of endovascular versus open repair of blunt traumatic aortic
      injuries.
AB  - BACKGROUND: Aortic injury is the second most common cause of death after blunt
      trauma. Thoracic endovascular aortic repair (TEVAR) has been rapidly adopted as
      an alternative to the traditional open repair (OR) for treatment of traumatic
      aortic injury (TAI). This paradigm shift has improved the outcomes in these
      patients. This study evaluated the outcomes of TEVAR compared with OR for
      patients with TAI. METHODS: We analyzed prospectively collected data from the
      institutional trauma registry between April 2002 and June 2010. These data were
      supplemented with a retrospective review of hospital financial accounts. The
      primary outcome was the presence or absence of any complication, including in
      hospital death. Secondary outcomes included fixed, variable, and total hospital
      costs and intensive care unit (ICU), preoperative, postoperative and total
      hospital length of stay (LOS). RESULTS: Amongst 106 consecutive patients (74 men;
      mean age, 36.4 years), 56 underwent OR and 50 underwent TEVAR for treatment of
      TAI. The proportion of patients who underwent TEVAR compared with OR increased
      from 0% to 100% during the study period. The TEVAR patients were significantly
      older than the OR patients (41.1 vs 32.2 years, P=.012). For patients who
      underwent TEVAR, the estimated odds ratio (95% confidence interval) of
      complications, including in-hospital mortality was 0.33 (0.11-0.97; P=.045)
      compared with the OR group. The average number of complications, including in
      hospital death, was higher in the OR group than in the TEVAR group (adjusted
      means, 1.29 vs 0.94). The OR group had a higher proportion of patients with
      complications, including in-hospital death, compared with the TEVAR group (69.6%
      vs 48%). Although, the mean adjusted variable costs were higher for TEVAR than
      for OR (P=.017), the mean adjusted fixed and total costs were not significantly
      different. Owing to a policy of delayed selective management, the adjusted
      preoperative LOS was significantly higher for TEVAR (9.8 vs 3.0 days, P=.022).
      The difference in the ICU or total hospital LOS was not significant. Although the
      proportion of uninsured patients was similar in both groups, the cohort (n=106)
      had a significantly higher proportion of uninsured patients (29% vs 5%) compared
      with the general vascular surgical population at our institution (0.29 vs 0.051,
      95% confidence interval for difference in proportions, 0.22-0.40; P<.0001).
      CONCLUSIONS: Compared with TEVAR, patients who underwent OR had three times
      higher odds to face a complication or in-hospital death. The mean total cost of
      TEVAR was not significantly different than OR. The findings support the use of
      TEVAR over OR for patients with TAI.

PMID- 23141679
TI  - Postoperative pain and early quality of life after radiofrequency ablation and
      mechanochemical endovenous ablation of incompetent great saphenous veins.
AB  - OBJECTIVE: Thermal ablative techniques of varicose veins carry a risk of heat
      related complications, including postoperative pain. Mechanochemical endovenous
      ablation (MOCA) might avoid these complications and reduce postoperative pain
      because of the absence of thermal energy. This study evaluated postoperative pain
      and quality of life after radiofrequency ablation (RFA) and MOCA for great
      saphenous vein (GSV) incompetence. METHODS: Sixty-eight patients with unilateral
      GSV incompetence were treated with either RFA or MOCA in this prospective
      observational study. Patients monitored their pain for the first 14 postoperative
      days on a 100-mm visual analog scale (VAS). They also completed the general (RAND
      36-Item Short-Form Health Survey) and disease-specific (Aberdeen Varicose Vein
      Questionnaire) quality of life questionnaires before and 6 weeks after treatment.
      RESULTS: Patients treated with MOCA reported significantly less postoperative
      pain than patients treated with RFA during the first 14 days after treatment (4.8
      +/- 9.7 mm vs 18.6 +/- 17.0 mm; P < .001) (mean VAS over 14 days). The lower
      postoperative pain score was associated with a significantly earlier return to
      normal activities (1.2 +/- 1.8 vs 2.4 +/- 2.8 days; P = .02) and work resumption
      (3.3 +/- 4.7 vs 5.6 +/- 5.8 days, respectively; P = .02). At 6 weeks, patients in
      both groups perceived an improved change in health status and an improved disease
      specific quality of life. CONCLUSIONS: MOCA is associated with significantly less
      postoperative pain, faster recovery, and earlier work resumption compared with
      RFA in the treatment of GSV incompetence. MOCA and RFA are both related to a
      rapid improvement in quality of life.

PMID- 23141680
TI  - Outcomes of an abdominal aortic aneurysm screening program.
AB  - OBJECTIVE: In 2007, Medicare guidelines were established to identify persons at
      risk for the presence of an abdominal aortic aneurysm (AAA). The purpose of this
      study is to evaluate the 5-year outcomes of an AAA screening program in a
      regional Veterans Affairs (VA) health care system. METHODS: Data were extracted
      from a regional VA health care network identifying all veteran males 65 to 75
      years of age who smoked at least 100 cigarettes during their lifetime. In 2007,
      an AAA screening mandate was implemented allowing patients meeting screening
      criteria to be evaluated for AAA as part of the patient's health maintenance. AAA
      is identified as an aortic diameter size of 3.0 cm or greater. Clinician
      adherence to screening protocols and referral to a vascular surgeon for aneurysms
      >5.5 cm were also evaluated. RESULTS: A total of 9751 patients (71.5 +/- 5.6
      standard deviation years of age) were screened for an AAA over a 5-year period
      from January 1, 2007 to December 31, 2011. A total of 698 aneurysms (7.1%) were
      found. Referrals to a vascular surgeon were made on 45 patients with aneurysms
      >5.5 cm. Over a 5-year period, a total of 2754 patients (28.2%) were
      inappropriately screened: 416 patients were under 65 years old, 2243 patients
      were over 75 years old, 36 patients were women, and 123 patients without
      aneurysms had multiple screenings. In 2007, during the first year of
      implementation, 39.2% of patients were inappropriately screened. Over the next 4
      years, inappropriate screenings decreased with 33.7% in 2008, 28.6% in 2009,
      17.7% in 2010, and 14.3% in 2011. CONCLUSIONS: A large AAA screening program at
      the VA detects more aneurysms, but at smaller diameters than that published in
      clinical trials. Over time, the number of inappropriate AAA screenings has
      continued to decrease, demonstrating greater awareness and application of the AAA
      screening guidelines by primary care providers. Developing surveillance
      guidelines for small and medium aneurysms is a potential area for future
      research.

PMID- 23141681
TI  - Cognitive outcome differences on the side of carotid artery stenting.
AB  - OBJECTIVE: The right and left sides of the brain play different roles in
      cognition. Therefore, the side of treatment should be taken into consideration
      when evaluating cognitive outcome following revascularization. Thus, we designed
      a study to evaluate changes in right hemisphere cognitive function in patients
      undergoing right carotid artery stentings (CAS) and left hemispheric cognitive
      function in patients undergoing left CAS. In addition, we studied CAS-related
      changes in regional cerebral blood flow to determine potential correlations with
      changes in cognitive function. METHODS: We performed a prospective assessment of
      39 CAS patients, all of whom were right-handed. Patients with contralateral
      stenotic lesions were excluded. Twenty-one patients underwent CAS of the right
      internal carotid artery (Right CAS group) and 18 underwent CAS of the left
      internal carotid artery (Left CAS group). Neuropsychological testing was
      performed preoperatively and 6 months after endovascular treatment. Cerebral
      blood flow was determined by 123I-labeled N-isopropyl-p-iodoamphetamine single
      photon emission computed tomography before and 6 months after CAS. RESULTS: In
      the Right CAS group, postoperative performance intelligence quotient score
      (91.1+/-18.2) was significantly improved compared with the preoperative score
      (84.9+/-16.7; P<.001). In the Left CAS group, postoperative verbal intelligence
      quotient score (104.0+/-18.8) was significantly higher than that before
      endovascular treatment (97.9+/-15.8; P<.005). Postoperative regional cerebral
      blood flow was not significantly different from that before endovascular
      treatment in either group. However, regional cerebrovascular reactivity of the
      treated side showed significant improvement after treatment. CONCLUSIONS:
      Amelioration of cognitive function may be dependent on the side of
      revascularization. Performance intelligence quotient improved after CAS in
      patients with severe carotid artery stenosis on the right side. Verbal
      intelligence quotient also improved on the left side after endovascular
      treatment. These effects seemed to involve improvement in regional
      cerebrovascular reactivity by CAS.

PMID- 23141682
TI  - Late Gore Excluder endoprosthesis fabric tear leading to abdominal aortic
      aneurysm rupture 5 years after initial implant.
AB  - Endoprosthesis fabric tear leading to abdominal aortic aneurysm rupture is a rare
      event. In this report, we describe a patient who presented with an abdominal
      aortic aneurysm rupture after a tear in the fabric of the Gore Excluder
      endoprosthesis (W. L. Gore and Associationes, Flagstaff, Ariz) 5 years after
      implantation. The reason for the fabric tear was unknown. The complication was
      successfully treated by relining the endograft with an aortic cuff and two iliac
      limbs. The patient experienced an uneventful recovery after the intervention.

PMID- 23141684
TI  - Fucoidan interferes with Porphyromonas gingivalis-induced aneurysm enlargement by
      decreasing neutrophil activation.
AB  - PURPOSE: Neutrophils have been shown to be involved in all stages of human and
      experimental abdominal aortic aneurysm (AAA) development. The initial processes
      of neutrophil rolling and trapping in the intraluminal thrombus (ILT) are
      mediated mainly by P-selectin expressed by activated platelets. In the present
      study, we propose to evaluate the beneficial effect of fucoidan, a competitive
      binding agent of P-selectin, on aneurysmal growth in a rat model of aortic
      aneurysm with neutrophil enrichment of the ILT induced by repeated episodes of
      weak bacteremia. METHODS: Sixty Lewis rats with experimental AAAs, developed from
      decellularized aortic xenografts, were divided into four groups. Two groups were
      used as controls: group fucoidan control (FC) was treated with 200 mg of fucoidan
      (F) delivered by 2 mL, 4-week osmotic pumps placed intraperitoneally before
      closing the abdomen, and group C received saline instead of fucoidan. Two more
      groups were injected weekly with Porphyromonas gingivalis (P. gingivalis [Pg]):
      group F+Pg received 200 mg of intraperitoneal fucoidan and group Pg received
      saline. AAAs were harvested after 4 weeks and peripheral blood was sampled at
      that time. Cell-free DNA (cf-DNA) and myeloperoxydase (MPO) antigen
      concentrations were determined in plasma and in AAA-conditioned media. Histology
      and P-selectin immunostaining were performed on AAA tissue samples. RESULTS:
      Comparing rats injected with Pg, those receiving fucoidan presented reduced
      aneurysmal diameter. Histologic analysis of AAAs showed that fucoidan reduced the
      ILT thickness in Pg-injected rats, with fewer trapped neutrophils, and with signs
      of a healing process, as observed in control group C. Immunohistological analysis
      revealed a substantial decrease in P-selectin immunostaining at the luminal
      surface of aneurysms in fucoidan-treated rats compared to the other groups,
      suggesting an interaction between fucoidan and P-selectin. A significant decrease
      in MPO concentrations in both plasma and conditioned medium was induced by
      fucoidan treatment in Pg-injected rats, reflecting a pacification of the ILT
      biological activity. This effect was associated with a reduction in neutrophil
      activation and apoptosis, reflected by a significant decrease in cf-DNA
      concentration in both plasma and conditioned medium of fucoidan-treated rats.
      CONCLUSIONS: Our results suggest that fucoidan has a beneficial effect on
      experimental aneurysmal degeneration by decreasing neutrophil activation in the
      ILT enhanced by weak pathogen contamination. This effect seems to be related to
      its interaction with P-selectin, which may decrease the trapping of neutrophils
      into the ILT. Fucoidan could represent a therapeutic option in AAAs to decrease
      the neutrophil activation involved in the degenerative process of aneurysmal
      expansion and rupture.

PMID- 23141685
TI  - Recruiting women to vascular surgery and other surgical specialties.
AB  - Vascular surgery is a subspecialty that attracts future surgeons with challenging
      technical procedures and complex decision making. Despite its appeal, continued
      promotion of the field is necessary to recruit and retain the best and brightest
      candidates. Recruitment of medical students and residents may be limited by the
      lifestyle inherent to vascular surgery and the length of residency training. The
      young adults of the current applicant and resident pool differ from prior
      generations in their desire for hands-on mentoring, aspirations to affect change
      daily, a penchant for technology, and strong emphasis on work-life balance.
      Furthermore, the percentage of women pursuing careers in vascular surgery is not
      representative of the eligible workforce. Women are now the majority of graduates
      in all of higher education, and thus, vascular surgery may need to make a
      concerted effort to appeal to women in order to attract the most talented young
      professionals to the field. Recruiting strategies for both men and women of
      Generation Y should target a diverse group of potential candidates with an
      awareness of the unique characteristics and needs of this generation of rising
      surgeons.

PMID- 23141686
TI  - Gene expression profiling of negative-pressure-treated skin graft donor site
      wounds.
AB  - Negative-pressure wound therapy (NPWT) is widely used to improve skin wound
      healing. Although NPWT has been studied as a treatment for wound closure and
      healing, the molecular mechanisms explaining its therapeutic effects remain
      unclear. To investigate the effect of NPWT on gene expression, and to discover
      the genes most dominantly responding to this treatment during skin wound healing,
      we applied negative pressure on split-thickness skin graft donor sites from the
      first postoperative day (POD) to the seventh POD. Biopsies were collected from 4
      NPWT-treated and 2 control patients. Two biopsy samples were taken from each
      patient: one from intact skin before graft harvesting, and one on the seventh POD
      from the donor site wound. Genome-wide microarrays were performed on all samples.
      Gene expression changes on the seventh POD were compared between NPWT and control
      patients, and were analyzed for statistical significance. In addition, we
      analyzed wound exudates for volume, and for concentrations of leukocytes,
      erythrocytes, and haemoglobin. NPWT induced major changes in gene expression
      during healing. These changes ranged from 10-fold induction to 27-fold
      suppression. The genes most induced were associated with cell proliferation and
      inflammation, and the most down-regulated genes were linked to epidermal
      differentiation. Our results provide the first insight into the molecular
      mechanisms behind NPWT, and suggest that NPWT enhances specific inflammatory gene
      expression at the acute phase associated with epithelial migration and wound
      healing. However, its continued use may inhibit epithelial differentiation.

PMID- 23141687
TI  - ICRP PUBLICATION 120: Radiological protection in cardiology.
AB  - Cardiac nuclear medicine, cardiac computed tomography (CT), interventional
      cardiology procedures, and electrophysiology procedures are increasing in number
      and account for an important share of patient radiation exposure in medicine.
      Complex percutaneous coronary interventions and cardiac electrophysiology
      procedures are associated with high radiation doses. These procedures can result
      in patient skin doses that are high enough to cause radiation injury and an
      increased risk of cancer. Treatment of congenital heart disease in children is of
      particular concern. Additionally, staff(1) in cardiac catheterisation
      laboratories may receive high doses of radiation if radiological protection tools
      are not used properly. The Commission provided recommendations for radiological
      protection during fluoroscopically guided interventions in Publication 85, for
      radiological protection in CT in Publications 87 and 102, and for training in
      radiological protection in Publication 113 (ICRP, 2000b,c, 2007a, 2009). This
      report is focused specifically on cardiology, and brings together information
      relevant to cardiology from the Commission's published documents. There is
      emphasis on those imaging procedures and interventions specific to cardiology.
      The material and recommendations in the current document have been updated to
      reflect the most recent recommendations of the Commission. This report provides
      guidance to assist the cardiologist with justification procedures and
      optimisation of protection in cardiac CT studies, cardiac nuclear medicine
      studies, and fluoroscopically guided cardiac interventions. It includes
      discussions of the biological effects of radiation, principles of radiological
      protection, protection of staff during fluoroscopically guided interventions,
      radiological protection training, and establishment of a quality assurance
      programme for cardiac imaging and intervention. As tissue injury, principally
      skin injury, is a risk for fluoroscopically guided interventions, particular
      attention is devoted to clinical examples of radiation-related skin injuries from
      cardiac interventions, methods to reduce patient radiation dose, training
      recommendations, and quality assurance programmes for interventional fluoroscopy.

PMID- 23141688
TI  - Writing a bachelor thesis generates transferable knowledge and skills useable in
      nursing practice.
AB  - Generic skills or transferable skills have been discussed in terms of whether or
      not skills learned in one context can be transferred into another context. The
      current study was aimed to explore nurses' self-perceptions of the knowledge and
      skills they had obtained while writing a Bachelor's thesis in nursing education,
      their experience of the extent of transfer and utilization in their current work.
      Responding nurses (N=42) had all worked from 1 to 1.5 years after their final
      examination and had completed a questionnaire that was structured with open-ended
      questions. Only five nurses reported that they were unable to use any of the
      knowledge and skills they had obtained from writing a thesis. A majority of the
      nurses (37/42) could give many examples of the practical application of the
      skills and knowledge they had obtained. Our findings indicate that writing a
      thesis as part of an undergraduate degree program plays a major role in the
      acquisition and development of knowledge and skills which can subsequently be
      transferred into and utilized in nursing practice.

PMID- 23141689
TI  - Challenges to student learning in the clinical setting: a qualitative descriptive
      study.
AB  - Clinical education is used throughout nursing to promote competency. Although
      this experience can be rewarding, students may face a variety of challenges
      within this context. The purpose of this qualitative descriptive study is to
      explore senior nursing students' perceptions of challenges to learning within the
      clinical setting. Three interrelated themes emerged from the data: (a) internal
      reactions to external limitations; (b) barriers experienced within the clinical
      environment; and (c) ineffective programme organisation. Findings are meant to
      guide educators and policy makers during decision making. The goal is advancement
      towards making the clinical environment a superior form of nursing education.

PMID- 23141690
TI  - Priming a molecular motor for disassembly.
AB  - In this issue of Structure, Oot and colleagues present the crystal structure of
      the eukaryotic V-ATPase peripheral stalk in complex with one of its binding
      partners, revealing conformational flexibility that may be important for priming
      the complex for rapid disassembly in response to external stimuli.

PMID- 23141691
TI  - Polo boxes come out of the crypt: a new view of PLK function and evolution.
AB  - Polo-like kinases (PLKs) are marked by C-terminal polo box modules with critical
      protein interaction and subcellular targeting roles. Slevin et al. in this issue
      of Structure reveal the architecture of a hidden set of polo boxes from the
      divergent PLK4, a critical player in centrosome duplication, shedding new light
      on the evolution of PLKs and their functionally related kinase ZYG-1.

PMID- 23141692
TI  - Retroviral intasomes: progress and questions.
AB  - In this issue of Structure, Gupta and colleagues apply a combination of
      biophysical approaches to study the solution properties of prototype foamy virus
      (PFV) integrase alone and in complex with viral DNA ends (intasome). The results
      complement and extend previous structural studies of PFV intasomes by X-ray
      crystallography and highlight the synergy of solution and crystallographic
      approaches to the study of nucleoprotein complexes.

PMID- 23141693
TI  - Structural data in synthetic biology approaches for studying general design
      principles of cellular signaling networks.
AB  - In recent years, high-throughput discovery of macromolecular protein structures
      and complexes has played a major role in advancing a more systems-oriented view
      of protein interaction and signaling networks. The design of biological systems
      often employs structural information or structure-based protein design to
      successfully implement synthetic signaling circuits or for rewiring signaling
      flows. Here, we summarize the latest advances in using structural information for
      studying protein interaction and signaling networks, and in synthetic biology
      approaches. We then provide a perspective of how combining structural biology
      with engineered cell signaling modules--using additional information from
      quantitative biochemistry and proteomics, gene evolution, and mathematical
      modeling--can provide insight into signaling modules and the general design
      principles of cell signaling. Ultimately, this will improve our understanding of
      cell- and tissue-type-specific signal transduction. Integrating the quantitative
      effects of disease mutations into these systems may provide a basis for
      elucidating the molecular mechanisms of diseases.

PMID- 23141694
TI  - Finding protein targets for small biologically relevant ligands across fold space
      using inverse ligand binding predictions.
AB  - Inverse ligand binding prediction utilizes a few protein-ligand (drug) complexes
      to predict other secondary therapeutic and off-targets of a given drug molecule
      on a proteomic scale. We adapt two binding site predictors, FINDSITE and SMAP, to
      perform the inverse predictions and evaluate them on over 30 representative
      ligands. Use of just one complex allows the identification of other protein
      targets; the availability of additional complexes improves the results. Both
      methods offer comparable quality when using three complexes with diverse
      proteins. SMAP is better when fewer complexes are available, while FINDSITE
      provides stronger predictions for smaller ligands. We propose a consensus that
      combines (and outperforms) the two complementary approaches implemented by
      FINDSITE and SMAP. Most importantly, we demonstrate that these methods
      successfully find distant targets that belong to structurally different folds
      compared to the proteins in the input complexes.

PMID- 23141695
TI  - Bolalipid fiber aggregation can be modulated by the introduction of sulfur atoms
      into the spacer chains.
AB  - The aggregation behavior in aqueous suspension of two symmetrical single-chain
      bolaamphiphiles, namely 12,21-dithiadotriacontane-1,32-diyl-bis [2-(tri
      methylammonio)ethylphosphate] (PC-C32SS-PC) and 12,21-dithiadotriacontane-1,32
      diyl-bis[2-(dimethylammonio)ethylphosphate] (Me(2)PE-C32SS-Me(2)PE), containing
      sulfur as heteroatoms in the chains, was studied using differential scanning
      calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), small angle
      neutron scattering (SANS), and transmission electron microscopy (TEM). The
      rheological properties of hydrogels formed by the aggregation into nanofibers
      were studied by oscillatory rheology. Based on the well-characterized behavior of
      bolalipids with long alkyl chains which at room temperature can form a network of
      nanofibers leading to the formation of a hydrogel, we investigated whether the
      incorporation of two heteroatoms of sulfur into the spacer chain of the molecules
      has an influence on the aggregation properties. Compared to the analogues without
      sulfur, the fibrous aggregates formed by sulfur containing compounds are less
      stable and build weaker viscoelastic gels. This is due to a perturbation of the
      packing of the chains as the sulfur atoms change the bond angle in the chain
      compared to the molecules with pure alkyl chains leading to kinks in the chain.
      For the bolaamphiphile with the Me(2)PE headgroups this effect is less pronounced
      due to the possibility of forming stabilizing hydrogen bonds between the
      headgroups.

PMID- 23141696
TI  - How pulse modes affect proton-barriers and anion-exchange membrane mineral
      fouling during consecutive electrodialysis treatments.
AB  - Mineral fouling of cation-exchange membrane (CEM) was recently reduced by pulsed
      electric fields (PEFs) during the electrodialysis (ED) of solutions containing
      high Mg(2+)/Ca(2+) ratios. However, a fouling layer appeared on the diluate side
      of anion-exchange membrane (AEM) once the pause lapse surpassed certain duration.
      Recent studies presented a multilayer mineral growth on CEM, but the case of AEM
      needs yet to be cleared. The current study reveals the mechanisms involved in AEM
      fouling growth when applying pulse modes of current in comparison with dc
      current. The results showed that dc current generated steady proton barriers
      given by water splitting at AEM interfaces that impeded fouling on both membrane
      sides. The higher frequency of PEF ratio 1 (Ton/Toff=10s/10s) acted removing
      completely an initial mineral deposit on the concentrate side of AEM, keeping it
      clean after two and three consecutive runs. Particularly, an undesirable brucite
      layer was formed on the AEM-diluate side for longer pause lapses as for a PEF
      ratio 0.3 (Ton/Toff=10s/33.3s) current regime. This structure caused violent
      water splitting resulting in amorphous magnesium hydroxide formation and
      consequently in fouling precipitation on the concentrate side during a third run
      through current exaltation.

PMID- 23141697
TI  - Solubility of gas in confined systems. Nonextensive thermodynamics approach.
AB  - The use of the concepts of the nonextensive thermodynamics allows reconsidering
      the equilibrium of bubble solubilization and more commonly of gaseous aggregates
      in supersaturated solutions of gas. The introduced relations are general and
      include as particular cases the equations usually used to describe these
      phenomena. These equations are discussed. Especially, we specified the domain of
      application of Kelvin's relation which was illustrated by the solubility of gases
      in fogs and clouds. Various possibilities of thoughts on the behavior of the
      gaseous aggregates and nano-systems are proposed. Thus, the introduced relations
      permit to consider the presence of gaseous aggregates in equilibrium with the
      solution even for under-saturated solution. Nonextensive thermodynamics admits
      the notion of negative pressure at the inner of confined phases (solid or
      liquid).

PMID- 23141698
TI  - Investigation of the problems with using gas adsorption to probe catalyst pore
      structure evolution during coking.
AB  - A common approach to try to understand the mechanism of coking in heterogeneous
      catalysts is to monitor the evolution of the pore structure using gas adsorption
      analysis of discharged pellets. However, the standard methods of analysis of gas
      adsorption data, to obtain pore-size distributions, make the key assumption of
      thermodynamically-independent pores. This assumption neglects the possibility of
      co-operative adsorption phenomena, which will shown to be a critical problem when
      looking at coking catalysts. In this work the serial adsorption technique has
      been used to detect and assess the extent of co-operative effects in adsorption
      within coking catalysts. The reaction of decane over a hydroprocessing catalyst
      was used as a case study. It has been shown that the conventional analysis method
      would lead to a flawed picture of the pore structure changes during the coking
      process. For the case-study considered in this work, it was found that co
      operative adsorption effects meant that 26% of the measured adsorption was
      occurring in pores up to three times larger than the size conventional analysis
      would presume. The serial adsorption technique was thus shown to provide
      important additional information on pore structure evolution during coking. A
      study of the kinetics of adsorption has been used to infer information about the
      general spatial location of the coking process within a pellet.

PMID- 23141699
TI  - Synthesis and physicochemical characterization of pyrrolidinium based
      surfactants.
AB  - Three new pyrrolidinium based surfactants were synthesized and characterized as
      pure aggregate components and in mixtures with 1,2-dimyristoyl-sn-glycero-3
      phosphocholine to understand how the molecular structure of the cationic
      amphiphile and its mole percentage might affect the physicochemical properties of
      the resulting aggregates. The thermotropic behavior of the mixed liposomes was
      investigated by differential scanning calorimetry on multilamellar vesicles,
      whereas their size and surface potential were investigated on large unilamellar
      vesicles by dynamic laser light scattering and fluorescence experiments,
      respectively. The presence of either methoxy or hydroxy groups in the positions 3
      and 4 of the pyrrolidinium ring as well as the presence of a second alkyl chain
      on pyrrolidinium nitrogen, controls the aggregates features.

PMID- 23141700
TI  - Hydrothermal synthesis and upconversion luminescence properties of beta
      NaGdF4:Yb3+/Tm3+ and beta-NaGdF4:Yb3+/Ho3+ submicron crystals with regular
      morphologies.
AB  - Single phase beta-NaGdF(4):Yb(3+)/Tm(3+) and beta-NaGdF(4):Yb(3+)/Ho(3+)
      submicron crystals with various morphologies including hexagonal prisms,
      spindles, and spheres were synthesized via the one-step hydrothermal method by
      controlling the pH values and sort of chelators (EDTA and citric acid). The
      prepared products showed intense up-converted luminescence (UCL) pumped by
      infrared laser at 980 nm. The hexagonal prisms that meaning high degree
      crystallinity demonstrated strong UCL in comparison with other morphologies such
      as spindles and spheres. In beta-NaGdF(4):Yb(3+)/Tm(3+), UCL not only appeared
      transitions from (1)G(4), (1)D(2), and (1)I(6) states to the lower lying states
      of Tm(3+), but also (6)P(J)->(8)S(7/2) transition (310 nm) of Gd(3+). These UCL
      were responsible for three, five, and six photons processes determined by pump
      power dependence of UCL intensities. The observation of UCL of Gd(3+) implied
      occurrence of energy transfer from Tm(3+):(1)I(6) to Gd(3+):(6)P(J).

PMID- 23141701
TI  - Micro-nano hierarchical superhydrophobic electrospray-synthesized silica layers.
AB  - This paper reports the preparation of superhydrophobic SiO(2) layers with a micro
      nano hierarchical surface structure. SiO(2) layers, which were rough on the
      microscale, were prepared using an electrospraying method combined with a sol-gel
      chemical route. To create a nanoscale structure, the surface of the SiO(2) layers
      was coated with Au nanoparticles using an ultraviolet-enhanced chemical reduction
      process, resulting in a micro-nano hierarchical surface structure. A subsequent
      fluorination treatment with a solution containing trichloro(1H,1H,2H,2H
      perfluorooctyl)silane resulted in fluorination of the micro-nano hierarchical
      SiO(2) layers. The resulting SiO(2) layers showed outstanding repellency toward a
      range of liquid droplets, for example, a water-repellency of 170 degrees . The
      surface fraction and work of adhesion of the fluorinated, micro-nano hierarchical
      SiO(2) layers were estimated using the Cassie-Baxter and Young-Dupre equations,
      respectively. The long-term durability and ultraviolet resistance of the
      superhydrophobic SiO(2) layers prepared in this study highlight their potential
      in a range of practical applications.

PMID- 23141703
TI  - Effects of freezing and thawing on the microstructure of latex paints.
AB  - Freeze-thaw (FT) cycles can aggregate particles in aqueous paint suspensions. To
      understand the mechanism of particle aggregation, cryogenic scanning electron
      microscopy (cryoSEM) was used to visualize the microstructure after the freezing
      and thawing steps of the FT cycle. After the freezing step, cryoSEM images show
      that the microstructure contains ice crystals and particle-rich regions. Adding
      propylene glycol, a FT stabilizing additive, leads to formation of larger ice
      crystals. After thawing, the dispersion structure revealed by cryoSEM shows that
      the particles redisperse only in the paint with the highest amount of propylene
      glycol. The other paints contain clusters that are different from the particle
      rich regions found after the freezing step. Increasing the thawing rate leads to
      a more dispersed microstructure even in the absence of propylene glycol. Analysis
      of the cryoSEM results shows that particle aggregation into these clusters occurs
      during the thawing stage, and slow thawing conditions lead to more aggregation.
      The cryoSEM results reported here are used to propose a mechanism of aggregation
      of particles in the paint.

PMID- 23141702
TI  - Significance of cell "observer" and protein source in nanobiosciences.
AB  - It is well understood that when nanoparticles (NPs) enter a biological medium,
      their surface is coated by various proteins; thus, the interaction of the living
      systems with the NPs depends on the composition of the protein layer, rather than
      the surface characteristics of the nanoparticle itself. However, there are
      several neglected parameters in protein-NP interactions (e.g., the key role of
      the protein source) that should be addressed. The composition of the protein
      corona is recognized as having a crucial influence on the delivery of NPs into
      cells, which is important in therapeutic applications and in nanotoxicology;
      however, the effect of "cell observer" (cell type) is poorly understood. This
      study probed the effects of different protein sources (fetal bovine serum [FBS]
      and human plasma [HP]) on the composition and protein thickness of the hard
      corona formed at the surface of superparamagnetic nanoparticles (SPIONs) with
      various sizes and surface chemistries. The results show that the hard corona can
      change quite considerably as one passes from the biophysicochemical properties of
      nanoparticles and protein sources (e.g., FBS and HP) appropriate to in vitro
      cell/tissue studies to those appropriate for in vivo studies. These changes in
      the hard corona have deep implications for in vitro-in vivo extrapolations. In
      addition, we probed the "cell observer" effect on the uptake and toxicity of
      SPIONs with the same protein corona composition to highlight the effect of cell
      type in nanobiosciences. The particles interacted with various cell lines. We
      find that without consideration of the "cell observer" effect, the cellular
      targeting/toxicity of NPs is inherently imprecise; thus, a deep understanding of
      both the protein corona composition and the "cell observer" effect offer a way to
      predict NP dosage for therapy and for the study of nanotoxins.

PMID- 23141704
TI  - Formation and structure of Langmuir-Blodgett films of organo-modified
      aluminosilicate with high surface coverage.
AB  - We have developed an effective organo-modification method at the organic
      solvent/distilled water interface of natural aluminosilicate clay surfaces. We
      also investigated the molecular arrangement of organo-modified aluminosilicate
      with high surface coverage in Langmuir-Blodgett films (LB) by performing out-of
      plane and in-plane X-ray diffraction (XRD) measurements. In addition, the surface
      morphology of mixed monolayers of organo-modified aluminosilicate and several
      biodegradable polymers (e.g., poly(L-lactide), PLLA) was also characterized by
      atomic force microscopy (AFM). The in-plane XRD results of multilayers of organo
      modified aluminosilicate formed by the LB method indicate the formation of a two
      dimensional lattice of hydrocarbons on the aluminosilicate surface. These
      hydrocarbons of organo-modified reagents packed hexagonal or orthorhombic in
      films. Based on our experimental findings, the LB technique enabled the formation
      of a densely packed organo-modified aluminosilicate monolayer at the water
      surface. Furthermore, for mixed monolayer systems comprising an organo-modified
      clay with high surface coverage and biodegradable polymers, a miscible surface
      was observed by AFM on a mesoscopic scale, whereas those with low surface
      coverage formed phase-separated structures.

PMID- 23141705
TI  - Colloidal lithography using silica particles: improved particle distribution and
      tunable wetting properties.
AB  - Colloidal lithography rests on the adhesion of colloids in a relatively ordered
      pattern on a charged surface owing to electrostatic interactions. However, due to
      capillary forces, the colloids tend to form aggregates during the drying process.
      These capillary forces are especially strong for large hydrophilic particles. In
      this paper, different experimental approaches are explored to limit the
      aggregation of large (500 nm) silica particles deposited on glass substrates that
      were previously treated with polyallylamine (PAH), a polycation. These approaches
      consist in the addition of smaller colloids between the large ones, or of a layer
      of macromolecules (PAH or albumin) on top of the deposit. Scanning electron
      microscopy observations show that the addition of PAH and even better of albumin
      on top of the adherent colloids efficiently limits the formation of aggregates.
      Interestingly, the water contact angle of the surface obtained after silica
      colloid deposition and albumin adsorption is very high (~95 degrees ), while very
      hydrophilic surfaces are obtained after calcination. This is discussed in light
      of the Wenzel and Cassie-Baxter models. In conclusion, the proposed method allows
      a nanoscale topographic pattern with tunable wettability to be created on large
      surface areas using a soft and inexpensive technique.

PMID- 23141706
TI  - A new method for fast intercalation of bulk crown ether guest into LDH.
AB  - Fast intercalation of macrocyclic tetraazacrown ether carboxylic acid derivative
      (TECA) into the interlayer of Mg/Al-layered double hydroxide (Mg/Al-LDH) via a
      "one-step" reaction in formamide was carried out. Compared with
      swelling/restoration and ion-exchange reactions, this method can markedly
      decrease the reaction time (even shorter than 10 min), thus give high yield of
      the products and well-retain the hexagonal morphology of the starting LDH. The
      investigation of the reaction process demonstrated that the preceding combination
      of TECA and formamide accelerated the swelling of LDH, and the quasi-homogeneous
      colloidal system promoted the facile incorporation of TECA with the LDH sheets to
      cause their quick restoration. The obtained staging structure may originate from
      the flexibility of crown ether guest and LDH host layer, and the structural
      transformation from homogeneous to second-staging suggests the Daumas-Herold
      model rarely observed in LDH system. The simple and fast one-step method can
      conveniently fabricate new multifunctional hybrid materials with combined
      advantages of the organic/inorganic intercalates plus those of LDH host.

PMID- 23141707
TI  - Gold surface supported spherical liposome-gold nano-particle nano-composite for
      label free DNA sensing.
AB  - Immobilization of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) liposome
      gold nano-particle (DOPE-AuNP) nano-composite covalently on 3-mercaptopropionic
      acid (MPA) on gold surface is demonstrated for the first time for electrochemical
      label free DNA sensing. Spherical nature of the DOPE on the MPA monolayer is
      confirmed by the appearance of sigmoidal voltammetric profile, characteristic
      behavior of linear diffusion, for the MPA-DOPE in presence of [Fe(CN)(6)](3-/4-)
      and [Ru(NH(3))(6)](3+) redox probes. The DOPE liposome vesicle fusion is
      prevented by electroless deposition of AuNP on the hydrophilic amine head groups
      of the DOPE. Immobilization of single stranded DNA (ssDNA) is made via simple
      gold-thiol linkage for DNA hybridization sensing in the presence of [Fe(CN)(6)](3
      /4-). The sensor discriminates the hybridized (complementary target hybridized),
      un-hybridized (non-complementary target hybridized) and single base mismatch
      target hybridized surfaces sensitively and selectively without signal
      amplification. The lowest target DNA concentration detected is 0.1*10(-12)M.
      Cyclic voltammetry (CV), electrochemical impedance (EIS), differential pulse
      voltammetry (DPV) and quartz crystal microbalance (QCM) techniques are used for
      DNA sensing on DOPE-AuNP nano-composite. Transmission Electron Microscopy (TEM),
      Fourier Transform Infrared Spectroscopy (FTIR), Atomic Force Microscopy (AFM),
      Dynamic Light Scattering (DLS) and Ultraviolet-Visible (UV) spectroscopic
      techniques are used to understand the interactions between the DOPE, AuNP and
      ssDNA. The results indicate the presence of an intact and well defined spherical
      DOPE-AuNP nano-composite on the gold surface. The method could be applied for
      fabrication of the surface based liposome-AuNP-DNA composite for cell
      transfection studies at reduced reagents and costs.

PMID- 23141709
TI  - Thermal Solid Sample Introduction-Fast Gas Chromatography-Low Flow Ion Mobility
      Spectrometry as a field screening detection system.
AB  - The potential of Thermal Solid Sample Introduction (TSSI)-Fast Gas Chromatography
      (GC)-Low Flow Ion Mobility Spectrometry (LF-IMS) having been designed and
      constructed in Engineering Research Center of Esfahan, detector group was
      investigated for chemical detection capabilities. Customizing the configuration
      of fast GC-IMS as a high technology, provides unique solutions for rapid
      detection of a broad range of chemical mixtures in many operational environments.
      TSSI configuration provides fast and easily applied method for direct detection
      with no additional sample preparation or extraction. The time required for total
      analysis, less than 265 s, was determined by the wide range of solid matrixes,
      including nitrate esters, nitroaromatics, and a nitramine. The fast extraction
      together with the short separation time limits degradation of the thermally
      labile compounds and decreases the peak widths, which results in larger peak
      intensities and a simultaneous improvement in detection limits. For signal-to
      noise ratio equals to 5, the detection limits for instrument for TNT, DNT and RDX
      were attained 15, 10 and 50 ng/MUl respectively. The combination of short
      analysis time and low detection limits make this instrument a potential candidate
      for field screening techniques.

PMID- 23141708
TI  - Immunogenicity of Salmonella enterica serovar Enteritidis virulence protein,
      InvH, and cross-reactivity of its antisera with Salmonella strains.
AB  - Acellular vaccines containing bacterial immunodominant components such as surface
      proteins may be potent alternatives to live attenuated vaccines in order to
      reduce salmonellosis risk to human health. invH gene, an important part of needle
      complex in type three secretion system (TTSS) plays important role in efficient
      bacterial adherence and entry into epithelial cells. In this work we hypothesize
      that use of a 15 kDa recombinant InvH as Salmonella enterica serovar Enteritidis
      surface protein could provoke antibody production in mouse and would help us
      study feasibility of its potential for diagnosis and/or a recombinant vaccine.
      The purified InvH provoked significant rise of IgG in mice. Active protection
      induced by immunization with InvH against variable doses of S. enterica serovar
      Enteritidis, indicated that the immunized mice were completely protected against
      challenge with 10(4) LD(50). The immunoreaction of sera from immunized mice with
      other Salmonella strains or cross reaction with sera of Salmonella strains
      inoculated mice is indicative of possessing by Salmonella strains of the surface
      protein, InvH, that can be employed in both prophylactic and diagnostic measures
      against S. enterica. Bacteria free spleen and ileum of the immunized mice in this
      study indicate that the invH gene affects bacterial invasion. Efficacy of the
      virulence protein, InvH, in shuttling into host cells in injectisome of S.
      enterica serovar Enteritidis and inhibition of this phenomenon by active
      immunization was shown in this study. In conclusion immunization with InvH
      protein can develop protection against S. enterica serovar Enteritidis
      infections. InvH in Salmonella strains can be exploited in protective measures as
      well as a diagnostic tool in Salmonella infections.

PMID- 23141710
TI  - Multiclass screening method based on solvent extraction and liquid chromatography
      tandem mass spectrometry for the determination of antimicrobials and mycotoxins
      in egg.
AB  - A QuEChERS (Quick Easy Cheap Effective Rugged Safe)-like extraction method was
      developed for the simultaneous analysis of veterinary drugs and mycotoxins in hen
      eggs by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with
      electrospray (ESI) source. Various classes of antimicrobials (tetracyclines,
      ionophores, coccidiostats, penicillins, cephalosporins, fluoroquinolones,
      sulfonamides) and mycotoxins (enniatins, beauvericin, ochratoxins, aflatoxins)
      were considered for the development of this method. Particular attention was
      devoted to extraction optimization: different solvents (acetone, acetonitrile and
      methanol), different pH values and different sample to extracting volume ratios
      were tested and evaluated in terms of recovery, relative standard deviation (RSD)
      and ESI signal suppression due to matrix effect. Chromatographic and mass
      spectrometric conditions were optimized to obtain the best instrumental
      performances for most of the analytes. Quantitative analysis was performed by
      means of matrix-matched calibration, in a range that varied depending on the
      analyte and its established maximum limit, when there was one. Recoveries at 100
      MUg kg(-1) spiking level were >62% (3<RSD<17) for all the antimicrobials except
      lasalocid A (41+/-10%) and oxacillin (56+/-17%). The multiclass method proposed
      is rapid, simple, and involves a low solvent consumption, in line with QuEChERS
      features and modern analytical requirements.

PMID- 23141711
TI  - Optimization of comprehensive two-dimensional gradient chromatography coupling in
      line hydrophilic interaction and reversed phase liquid chromatography.
AB  - In-line coupled comprehensive HILIC*RP systems should offer larger selectivity
      differences and better two-dimensional orthogonality than coupled RP*RP systems.
      However, this may not apply for all systems. The HILIC selectivity depends on the
      mix of selective polar and non-polar interactions with the functional groups, but
      also with the matrix of polar columns and depends on the sample type. We
      synthesized a new polar monolithic sulfobetaine polymethacrylate capillary column
      with excellent efficiency for low-molecular compounds. When used in the first,
      HILIC dimension coupled to core-shell or monolithic RP columns in the second
      dimension, this column provides much improved orthogonality for two-dimensional
      separations of phenolic and flavonoid compounds, in comparison to silica-bonded
      Diol, Polyethylene glycol or Zwitterionic columns. We investigated the
      performance of 11 short 5 cm and 3 cm columns for fast (1-2 min) gradient second
      dimension separations. Band broadening or distortion may occur in directly
      coupled comprehensive HILIC*RP systems, due to strong solvent-strength
      differences between the mobile phases used in the first and in the second
      dimension. To suppress this effect, low fraction volumes were collected from a
      0.5mm I.D. capillary monolithic sulfobetaine column at the flow-rate of a few
      microliters per min, coupled in-line with various core-shell columns operated at
      the maximum flow-rate. This setup with simultaneous gradient elution in the HILIC
      and in the RP dimension provided successful separation of natural antioxidants.

PMID- 23141712
TI  - Acute heel pain related to apatite deposition in the plantar fascia.

PMID- 23141713
TI  - Microchimerism and rheumatic diseases.

PMID- 23141714
TI  - Licensing of antirheumatic drugs: are the EMA and FDA on the same page?

PMID- 23141715
TI  - SAPHO syndrome and collagenous colitis.

PMID- 23141716
TI  - Prevotella is not so kind.

PMID- 23141717
TI  - The relationship between peripheral arthritis and anti-cyclic citrullinated
      peptide antibodies in ankylosing spondylitis.
AB  - OBJECTIVES: Although ankylosing spondylitis (AS) primarily affects the axial
      skeleton, peripheral arthritis occurs in up to 35% of cases. Anti-cyclic
      citrullinated peptide (anti-CCP) antibodies are highly specific for rheumatoid
      arthritis, whereas their role in AS remains unclear. In this study we aimed to
      assess the prevalence of anti-CCP antibodies in AS patients with peripheral
      arthritis and their clinical association with peripheral arthritis. METHODS: We
      retrospectively selected for this study 625 AS patients who fulfilled the
      modified New York criteria. The patients were divided into those with and those
      without peripheral arthritis on smoking history, the basis of symptoms, physical
      examination and medical records. The presence of anti-CCP antibodies was
      investigated in all the patients. RESULTS: Anti-CCP antibodies were found in 4%
      (25/625) of the patients, and peripheral arthritis was diagnosed in 37.4%
      (234/625) of the patients. In multiple logistic regression, peripheral arthritis
      was significantly associated with female gender (P = 0.001) and the presence of
      anti-CCP antibodies (P = 0.001), especially with the presence of titers of anti
      CCP antibodies over three times the normal upper limit of the laboratory and
      assay. CONCLUSIONS: Anti-CCP antibodies are occasionally present in AS, and their
      presence may be helpful as a serum marker for predicting peripheral arthritis.

PMID- 23141718
TI  - Meta-analysis of clinical and radiological efficacy of biologics in rheumatoid
      arthritis patients naive or inadequately responsive to methotrexate.
AB  - Our aim was to compare all eight biologics available for rheumatoid arthritis in
      two patient populations, methotrexate-naive patients and inadequate responders to
      methotrexate, based on a comprehensive literature review. The five TNFalpha
      antagonists, rituximab, abatacept and tocilizumab used with methotrexate were
      compared to methotrexate monotherapy using the ACR50 response as the primary
      clinical endpoint and absence of radiographic progression after 1 year as the
      primary radiological endpoint. Odds ratios (ORs) were computed, as well as the
      number needed to treat (NNT) to obtain an ACR50 response for each biologic. We
      included 22 studies. Overall, combined biologic therapy was significantly more
      effective than methotrexate alone in both the naive group (OR: 2.11; 95%
      confidence interval [95%CI], 1.85-2.41) and the unresponsive group (OR: 4.82;
      95%CI: 3.83, 6.08). Crude NNTs were as follows: etanercept, five in the naive
      group and three in the unresponsive group; adalimumab, seven and three;
      infliximab, seven and five; abatacept, seven and four; rituximab, five and five;
      and tocilizumab and certolizumab, four in the unresponsive group. None of the
      differences was statistically significant. In the naive group, combined biologic
      therapy was associated with a higher rate of absence of radiographic progression
      after 1 year compared to methotrexate alone (OR: 2.19; 95%CI: 1.55-3.08). All
      biologics had approximately the same efficacy. Methotrexate-naive patients
      treated with biologics had significantly less radiographic progression than those
      with cellular therapy. 

PMID- 23141719
TI  - Modulation of hepatitis C virus RNA abundance and virus release by dispersion of
      processing bodies and enrichment of stress granules.
AB  - Components of cytoplasmic processing bodies (P-bodies) and stress granules can be
      subverted during viral infections to modulate viral gene expression. Because
      hepatitis C virus (HCV) RNA abundance is regulated by P-body components such as
      microRNA miR-122, Argonaute 2 and RNA helicase RCK/p54, we examined whether HCV
      infection modulates P-bodies and stress granules during viral infection. It was
      discovered that HCV infection decreased the number of P-bodies, but induced the
      formation of stress granules. Immunofluorescence studies revealed that a number
      of P-body and stress granule proteins co-localized with viral core protein at
      lipid droplets, the sites for viral RNA packaging. Depletion of selected P-body
      proteins decreased overall HCV RNA and virion abundance. Depletion of stress
      granule proteins also decreased overall HCV RNA abundance, but surprisingly
      enhanced the accumulation of infectious, extracellular virus. These data argue
      that HCV subverts P-body and stress granule components to aid in viral gene
      expression at particular sites in the cytoplasm.

PMID- 23141720
TI  - Molecular epidemiology of betanodavirus-sequence analysis strategies and
      quasispecies influence outbreak source attribution.
AB  - The quasispecies structure of nervous necrosis virus (NNV) was determined to
      investigate an outbreak of viral nervous necrosis disease at a barramundi (Lates
      calcarifer) hatchery. A traditional epidemiological investigation indicated
      horizontal transmission of infection between two cohorts of fish. However,
      variation in the viral capsid protein gene sequence from cell culture-derived
      viral populations and from individual fish suggested that each cohort was
      infected with a different virus. Molecular support for the correct
      epidemiological conclusion was provided by determining the consensus NNV sequence
      directly from multiple fish, to show that each cohort was infected with the same
      quasispecies. Variation in the capsid gene of isolates obtained from this
      quasispecies was up to 3.3% compared with sequences determined directly from fish
      tissue, and <=1.7% between individual fish within each cohort. Determination of
      the NNV quasispecies structure supported implementation of biosecurity measures
      to protect fish in the hatchery from environmental sources of infection.

PMID- 23141721
TI  - New insights into small RNA-dependent translational regulation in prokaryotes.
AB  - Bacterial small RNAs (sRNAs) typically repress translation of target mRNAs by
      pairing directly to the ribosome-binding site (RBS) and competing with initiating
      ribosomes, an event that is often followed by rapid mRNA decay. In recent years,
      however, many examples of translation-repressing sRNAs pairing outside the RBS
      have been described. In this review, we focus on newly characterized mechanisms
      that explain how a sRNA can modulate translation by binding outside of the RBS
      and discuss new insights into the events following translation repression. These
      new mechanisms broaden current perspectives of sRNA pairing sites on mRNA targets
      and demonstrate how the interplay between sRNAs, mRNA structures, and protein
      partners can contribute to post-transcriptional regulation.

PMID- 23141722
TI  - [Comparison of treatment effect between periodontal subgingival scaling with the
      special series of ultrasonic inserts and Gracey curette].
AB  - OBJECTIVE: To compare the special series of ultrasonic inserts with Gracey
      curettes in the effectiveness and efficiency for non-surgical periodontal
      treatment. METHODS: A total of 30 patients with moderate to advanced chronic
      periodontal disease were treated with both ultrasonic inserts (ultrasonic group)
      and Gracey curettes (Gracey group) according to a prospective, randomized,
      controlled, one-blind, "split-mouth" design. Twenty-six cases were available for
      the whole follow-up period. Plaque index (PLI), bleeding index(BI), probing depth
      (PD), attachment loss (AL) were evaluated before and 6 weeks after treatment.
      Treatment time was recorded. The severity of pain during treatment and teeth
      sensitivity after treatment were evaluated by the visual analogue scale (VAS).
      Differences in clinical parameters were analyzed with the Wilcoxon signed ranks
      test and Mann and Whitney U-test. RESULTS: No significant differences in any of
      the clinical parameters were observed at baseline between the two groups. The
      mean value of PD, BI, PLI, AL decreased in both ultrasonic group and Gracey
      group. At moderately deep site (initial PD between 4 mm and 5 mm), PD [M(Q(25),
      Q(75))] changed in the ultrasonic group from 4.0 (4.0, 4.5) mm to 3.0 (3.0, 3.0)
      mm (P < 0.001) and in the Gracey group from 4.0 (4.0, 5.0) mm to 3.0(3.0, 3.0) mm
      (P < 0.001). At deep sites (initial PD >= 6 mm) PD [M(Q(25), Q(75))] changed in
      the ultrasonic group from 7.0(6.0, 7.0) mm to 5.0(4.0, 7.0) mm (P < 0.001) and in
      the Gracey group from 7.0 (6.0, 7.0) mm to 5.0(4.0, 6.0) mm(P < 0.001). In the
      furcation area, PD [M(Q(25), Q(75))] changed from 5.0(4.0, 7.0) mm to 3.0(3.0,
      5.0) mm (P < 0.001) in both Gracey group and ultrasonic group. However, the
      average time of active instrumentation was (2.41 +/- 0.61) min/tooth in the
      ultrasonic scaling and (2.71 +/- 0.61) min/tooth in the Gracey curette (P <
      0.001). VAS scores [M(Q(25), Q(75))] of pain during treatment was 5.0(3.0, 6.7)
      in the ultrasonic group and 5.9 (4.9, 8.0) in the Gracey group (P = 0.001). VAS
      scores [M(Q(25), Q(75))] of sensitivity after treatment was 4.0 (1.8, 6.0) in the
      ultrasonic group and 4.9 (2.0, 8.0) in the Gracey group (P = 0.043). CONCLUSIONS:
      Treatment with the special series of ultrasonic inserts was as effective as the
      Gracey curette during initial therapy period in all clinical parameters measured
      and has the advantage of being quicker.

PMID- 23141723
TI  - [Effect of minocycline hydrochloride ointment on cell attachment and
      proliferation on titanium disks].
AB  - OBJECTIVE: To investigate the effect of minocycline hydrochloride ointment on
      cell attachment and proliferation on titanium disks. METHODS: Commercially pure
      (grade 4) machined titanium discs with three different kinds of surfaces (smooth,
      acid-etched and sandblasted combined with acid-etched) were treated with
      minocycline ointment for 1 week, and then cleaned in ultrasonic cleanser for 10
      minutes. Surface properties were examined by scanning electron microscope (SEM)
      and roughness tester before and after the treatment. Surface roughness was
      compared by paired t test. MG-63 (human osteoblast-like osteosarcoma cell) cells
      were seeded on these three kinds of discs with or without minocycline treatment,
      and methl thiazolyl tetrazolium (MTT) was performed to investigate the attachment
      in the 1st day and proliferation in the 4th and 7th day. Data were analyzed by
      double factor analysis of variance. RESULTS: Surface roughness before and after
      minocycline application was as follows, Smooth: (0.093 +/- 0.025) um, (0.086 +/-
      0.026) um; Acid-etched: (1.100 +/- 0.095) um, (1.009 +/- 0.196) um; Sandblasted
      combined with acid-etched: (2.837 +/- 0.283) um, (2.968 +/- 0.206) um. No
      significant changes in roughness were found before and after minocycline
      application (P values were 0.118, 0.436 and 0.692). SEM examination revealed as
      similar surface configuration after minocycline application as before, except for
      some remnant of the minocycline ointment in acid-etched and sandblasted combined
      acid-etched groups. In MTT test, the growth of MG-63 cells in the 1 st, 4th day
      and 7th day was not different between groups with and without minocycline
      application (P values were 0.450, 0.848 and 0.835), and among three groups of
      different surface (P values were 0.184, 0.579 and 0.331). CONCLUSIONS:
      Minocycline hydrochloride ointment did not affect the surface configuration,
      surface roughness or the properties for cell attachment and proliferation of
      titanium discs.

PMID- 23141724
TI  - [Expression of cytokines of interleukin-6 family in gingival fibroblasts by Toll
      like receptor-2].
AB  - OBJECTIVE: To investigate whether signaling through Toll-like receptor-2 (TLR-2)
      can affect the expression of some cytokines in human gingival fibroblasts.
      METHODS: The gingival fibroblasts were isolated and cultured in vivo, divided
      into blank control group, lipopolysaccharide (LPS) from Porphyromonas gingivalis
      (Pg) group and Escherichia coli (Ec) group. mRNA expression levels were measured
      by real-time polymerase chain reaction (PCR). The protein expression levels were
      detected by the enzyme linked immunosorbent assay (ELISA). The data was
      statistically analyzed by SPSS16.0 software package. RESULTS: LPS from Pg could
      stimulate the expression of interleukin (IL)-6 and leukemia inhibitory factor
      (LIF) mRNA and protein, which reached the peak (5.87 +/- 0.83) at 10 h, and the
      expression level increased with the increase of the Pg concentration. IL-11 or
      oncostatin-M (OSM) mRNA expression was not affected by LPS. After treated with Pg
      for 48 h, the protein expression of IL-6 and LIF was up-regulated, (962 +/- 57)
      ng/L and (47 +/- 18) ng/L respectively. CONCLUSIONS: Signaling through TLR-2
      controls the expression of cytokines of IL-6 family in human gingival
      fibroblasts.

PMID- 23141725
TI  - [Root and alveolar bone status of maxillary labial inverted impacted incisor in
      mixed dentition after orthodontic treatment].
AB  - OBJECTIVE: To study the alveolar bone surrounding situation and the length of the
      root of the maxillary labial inverted impacted incisor in mixed dentition after
      orthodontic treatment. METHODS: Fourteen cases with maxillary labial inverted
      impacted incisor in mixed dentition were collected. Modified Nance arch and
      conventional appliance were used. Cone-bean CT (CBCT) was taken after the
      treatment. Simplant13.0 three-dimensional reconstruction and multi-planer
      reconstruction (MPR) method were used to observe the labial and lingual alveolar
      bone crest morphology, besides, the labial and lingual length from the alveolar
      bone crest to cemento-enamel junction (CEJ) of the impacted incisor and the
      homonym tooth after treatment, along with their root length and their labial and
      lingual length ratio of the root surrounded by the alveolar bone to the total
      root length were measured. The idependent samples t-test were used to analyze the
      variable differences. RESULTS: The labial and lingual alveolar bone of fourteen
      cases crest of the diseased tooth after treatment presented general symmetry U
      shape from qualitative observation through the three-dimensional reconstruction.
      The labial and the lingual length of the diseased incisor from alveolar bone
      crest to CEJ [(2.47 +/- 1.35) and (1.47 +/- 0.84) mm] was significant increased
      than those of the homonym incisor [(1.03 +/- 0.35) and (0.90 +/- 0.37) mm] (P <
      0.05); the length of the diseased incisor's post-treatment root [(9.82 +/- 2.82)
      mm] was no statistically significant decreased than that of the homonym incisor
      root [(10.28 +/- 1.38) mm, P = 0.59]; the labial and the lingual length ratio of
      the impacted tooth's root surrounded by the alveolar bone to the total root
      length [(72.83 +/- 17.16)% and (85.32 +/- 5.98)%] was statistically significant
      decrease than those of homonym teeth[(89.66 +/- 3.98)% and (90.84 +/- 4.61)%] (P
      < 0.05). CONCLUSIONS: The diseased tooth's root had gotten enough length after
      the treatment. The labial and lingual alveolar bone of the maxillary labial
      inverted impacted incisor in mixed dentition can't offer sufficient adaptive
      hyperplasia after treatment, of which labial alveolar bone is more apparent,
      prompting careful protection when they were used.

PMID- 23141726
TI  - [Detection of marginal leakage of Class V restorations in vitro by micro-CT].
AB  - OBJECTIVE: To evaluate the reliability and superiority of micro-CT in marginal
      leakage assessment of Class V restorations. METHODS: Class V preparations with
      gingival margins in dentin and occlusal in enamel were made in sixteen extracted
      non-carious human molars and restored with dental bonding agents and composite
      resin. All teeth were then immersed in 50% ammonia-silver nitrate solution for 12
      hours, followed by developing solution for 8 hours. Each restoration was scanned
      by a micro-CT and silver leakage was measured and three-dimensional image of the
      silver leakage alone cavity wall were reconstructed. Afterward, all restorations
      were sectioned and examined for leakage depth using a microscope. The silver
      leakage depth of each restoration obtained by micro-CT and microscope were
      compared for equivalency. RESULTS: The silver leakage depths in gingival wall
      obtained with micro-CT (0.78 mm) and microscope (0.74 mm) showed no significant
      difference (P > 0.05), while the judgment of leakage depths in occlusal wall in
      micro-CT image (0.40 mm) was affected by adjacent enamel structure, giving less
      leakage depths compared to microscope (0.72 mm)(P < 0.01). The three-dimensional
      shapes of the microleakages displayed clearly by micro-CT alone wall of Class V
      restorations were multiform and some leakages showed channels on their way to
      spreading. CONCLUSIONS: Micro-CT can detect precisely the silver leakage in the
      dentin wall of a restoration and display its three-dimensional shape fully.
      Enamel structure affects the detection of the silver leakage next to it.

PMID- 23141727
TI  - [Scanning electron microscope analysis of the root dentin bonding interface
      filled with different pastes or bonded by different program in fiber post and
      resin bonded repair].
AB  - OBJECTIVE: To observe the influence of different bonding process and three
      different root canal sealing materials on microstructure of root canal dentin
      bonding interface after fiber post and resin bonding, so as to improve clinical
      operation steps and to optimize fiber post resin bonding effect. METHODS: Fifteen
      human single mandibular first premolars were selected. Three were bonded with
      fiber posts through Relyx Unicem conventional bonding steps after filled with
      root canal sealing materials of zinc oxide eugenol paste (Group A), and another
      three were bonded through the same steps after filled with sealing materials of
      Vitapex (Group B). The other nine were filled with sealing materials of AH Plus,
      randomly divided into three groups and bonded through different steps as follows:
      conventional bonding steps only (Group C), etching with 35% phosphoric acid
      before conventional bonding steps (Group D), and etching and coating with
      Singlebond 2 adhesive before conventional bonding steps (Group E). After immersed
      in saline solution for one week, all the roots were cut into three sections of 3
      mm in thickness with emery chip and numbered as crown section, middle section and
      tip section respectively. The samples were observed the resin protrusion in mixed
      layer of dentin interface and dentinal tubules by scanning electron microscopy.
      RESULTS: We observed the resin protrusion in microstructures of the roots bonded
      through Relyx Unicem after filled with three different root canal sealing
      materials (Group A, B, C, E): most obvious in the root crown sections, middle in
      the root middle sections and least in the root tip sections. Differences were
      observed in roots filled with different sealing materials: little resin
      protrusion were observed in crown sections only in Group A and B, but large
      number of resin protrusion were found in crown and middle sections in Group C-E.
      Compared with Group C, no more resin protrusion were found in Group D. More and
      elongated resin protrusions were found in Group E. CONCLUSIONS: We recommend
      using AH Plus as root canal sealing materials for residual crown and root needed
      to strengthen by fiber post. It is no need to etch before Relyx Unicem
      conventional bonding steps. However, coating Singlebond 2 adhesive after acid
      etching has the potential to increase fiber post cementation.

PMID- 23141728
TI  - [Reconstruction of anterior mouth floor defects with depressor labii inferioris
      flap: a preliminary report].
AB  - OBJECTIVE: To investigate the method and efficacy of reconstruction of anterior
      mouth floor defects with depressor labii inferioris flap. METHODS: Between March
      2010 and August 2011, 4 patients with cancer in the anterior part of oral floor
      underwent tumour resection and simultaneous reconstruction with depressor labii
      inferioris flap. The patients were followed up for 2 - 18 months. The survival of
      the flaps, mobility of tongue and esthetic outcome of lip and mental region were
      evaluated. RESULTS: All the flaps survived completely, tongues moved well, and
      functional and esthetic results were good. CONCLUSIONS: The depressor labii
      inferioris flaps are suitable for repairing defects of anterior oral floor.

PMID- 23141729
TI  - [Experimental study on ectopic prefabrication of vascularized mandible graft with
      autogenous ribs].
AB  - OBJECTIVE: To explore a method for ectopic prefabrication of mandible with
      vascular pedicle. METHODS: Cancellous bone blocks harvested from the dog ribs
      were packaged with mandible-shaped titanium mesh scaffold and implanted into
      latissimus dorsi of dog with thoracodorsal artery and vein through the scaffold.
      After 12 weeks, bone formation and vascularization were evaluated by gross
      inspection, histological examination and immunohistochemistry. RESULTS:
      Vascularized mandible with thoracodorsal artery and vein were formed and
      histological staining and immunohistochemisty confirmed new bone formation and
      vascularization. CONCLUSIONS: There is feasibility for ectopic prefabrication of
      vascularized mandible graft using cancellous ribs, which provides a new method
      for mandibular defect reconstruction. Experimental study on ectopic
      prefabrication of vascularized mandible graft with autogenous ribs.

PMID- 23141730
TI  - [Genetic diversity of ATP synthase cab subunits amplified from Streptococcus
      mutans clinical isolates from Uyghur children with different caries
      susceptibility].
AB  - OBJECTIVE: To investigate the aciduricity and genetic diversity of ATP synthase
      subunit gene uncEBF derived from Uyghur children Streptococcus mutans (Sm)
      clinical isolates and the relationship between the genetic diversity of ATP
      synthase and Sm aciduric ability and caries susceptibility. METHODS: Forty-one Sm
      strains derived from 24 caries-active individuals and 17 caries-free individuals,
      including 16 strains displaying high acid tolerance and 17 strains displaying low
      acid tolerance. Solutions of all isolated Sm with same density were made and
      cultured at pH 4.0 to 7.0 brain heart infusion (BHI) liquid. Terminal growth
      situation was compared. Gene uncEBF of these isolates were amplified with
      specific primers from Sm genomic DNA, and the polymerase chain reaction (PCR)
      products were analyzed by PCR-restriction fragment length polymorphism (RFLP) and
      sequenced. RESULTS: Aciduric ability of Sm isolated from the high caries
      susceptible children were higher than that isolated from caries-free group (P =
      0.023). Alu I digested fragments of uncEBF displayed two different patterns A and
      B. The distributions of A and B genotype strains with different acidurance were
      different (P = 0.039). A genotype included 7 strains displaying high acid
      tolerance and 2 strains displaying low acid tolerance;B genotype included 9
      strains displaying high acid tolerance and 15 strains displaying low acid
      tolerance. The distributions of A and B genotype strains in different caries
      sensitivity groups were different (P = 0.009). A genotype included 7 high caries
      susceptible strains and 12 caries-free strains; B genotype included 17 high
      caries-susceptible strains and 5 caries-free strain. Some of these amplified
      uncEBF genes from different genotype were sequenced and testified that there
      existed variation of Alu I recognized sites. CONCLUSIONS: The high cariogenecity
      of Sm strains isolated from caries-active children shows a close relationship
      with the high aciduric ability of the isolated Sm strains. uncEBF gene of Sm F
      ATPase obviously exhibits genetic diversity.

PMID- 23141731
TI  - [Calcium hydroxide regulates bone sialoprotein gene transcription in human dental
      pulp cells].
AB  - OBJECTIVE: To analyze the effects of calcium hydroxide [Ca(OH)2] on transcription
      of the bone sialoprotein (BSP) gene in human dental pulp cells. METHODS: Human
      dental pulp tissues were collected from extracted teeth for orthodontic reason.
      In cell culture media, different dose (0.012, 0.120, 0.400 and 1.200 mmol/L) of
      Ca(OH)2 was added. Total RNA of cells were extracted. The best dose of Ca(OH)2 on
      human BSP was determined with the real-time polymerase chain reaction (PCR).
      Further, the time (0, 3, 6, 12, 24 h) effects of the best dose Ca(OH)2 on human
      BSP, runt-related transcription factor-2 (Runx-2) and osterix (OSX) mRNA levels
      were determined with PCR. Further method included transient transfection assays,
      linking chimeric constructs of the human BSP gene promoter to a luciferase
      reporter gene, then ransfected using lipofectamine in cells and measured the
      luciferase activities of BSP gene promoter. RESULTS: With the real-time PCR, the
      optimal Ca(OH)2 concentration was determined as 1.200 mmol/L. With this
      concentration at different time points (0, 3, 6, 12 and 24 h), the levels of BSP
      mRNA increased at 6 h (1.45 +/- 0.36), reached maximal at 12 h (2.66 +/- 0.18);
      the levels of Runx-2mRNA increased at 6 h (2.38 +/- 0.08), at 12 h (2.73 +/-
      0.16), and decreased at 24 h. OSX mRNA could be recognized at 12 h, reached
      maximal levels at 24 h (3.30 +/- 0.062). Transient transfection assays showed
      that treatment of human dental pulp cells with Ca(OH)2 (1.200 mmol/L) increased
      the luciferase activities of the constructs between -84LUC and -868LUC at 12 h
      (2.00 ~ 2.60 fold). CONCLUSIONS: This study demonstrate that Ca(OH)2 could
      stimulate BSP transcription between -84LUC and -868LUC in the human BSP gene
      promoter in human dental pulp cells.

PMID- 23141732
TI  - [Corrosion resistance of casted titanium by compound treatments in the artificial
      saliva with different fluoride concentrations].
AB  - OBJECTIVE: To study the corrosion resistance of casted titanium by plasma
      nitriding and TiN-coated compound treatments in the artificial saliva with
      different fluoride concentrations and to investigate whether compound treatments
      can increase the corrosion resistance of casted titanium. METHODS:
      Potentiodynamic polarization technique was used to depict polarization curve and
      to measured the current density of corrosion (Icorr) and the electric potential
      of corrosion (Ecorr) of casted titanium (Group A) and casted titanium by compound
      treatments (Group B) in the artificial saliva with different fluoride
      concentrations. After electrochemical experiment, the microstructure was observed
      by scanning electron microscope (SEM). RESULTS: The Icorrs of Group A and B in
      the artificial saliva of different fluoride concentrations were (1530.23 +/-
      340.12), (2290.36 +/- 320.10), (4130.52 +/- 230.17) nA and (2.62 +/- 0.64), (7.37
      +/- 3.59), (10.76 +/- 6.05) nA, respectively. The Ecorrs were (-0.93 +/- 0.10), (
      0.89 +/- 0.21), (-0.57 +/- 0.09) V and (-0.21 +/- 0.04), (-0.17 +/- 0.03), (-0.22
      +/- 0.03) V, respectively.The Icorrs of Group B were significantly lower (P <
      0.01)than that of Group A. The Icorrs increased significantly with the increasing
      of fluoride concentrations (P < 0.01). The Ecorrs of Group B were significantly
      higher than that of Group A (P < 0.01). The SEM confirmed the microstructure in
      the casted titanium was much severely than that in Group B, the microstructure in
      Group A and B corroded more and more heavily with increasing of fluoride
      concentrations. CONCLUSIONS: The increase of fluoride concentrations influence
      the corrosion resistance of both treated and untreated casted titanium
      negatively, but plasma nitriding and TiN-coated compound treatments can
      significantly increase the corrosion resistance of casted titanium.

PMID- 23141733
TI  - [Effects of DNAX-associated protein 12 signal pathways on differentiation of
      mouse monocytes RAW264.7 into osteoclasts by tensile strain].
AB  - OBJECTIVE: To explore the effect of DNAX-associated protein 12 (DAP12) pathway on
      the transformation from mouse monocytes RAW264.7 to osteoclasts induced by
      tensile strain. METHODS: DAP12shRNA plasmid was constructed and introduced to
      RAW264.7 cells. Then we supplied tensile strain to RAW264.7 cells by four-point
      bending system. The mRNA or protein expression of DAP12, tartrate-resistant acid
      phosphatase (TRAP), tyrosine kinases Btk and Tec and nuclear facior of activated
      T cells 1 (NFATc1) was measured by reverse transcription PCR (RT-PCR) and Western
      blotting respectively. RESULTS: The expression of DAP12 mRNA (0.112 +/- 0.025)
      and protein (0.193 +/- 0.015) both declined sharply after plasmid being
      introduced into monocytes RAW264.7 (P < 0.05). After silencing DAP12 expression
      in RAW264.7 cells by RNA interference, tensile strain-induced TRAP mRNA
      expression of RAW264.7 cells increased at 6 h (0.671 +/- 0.031) and 12 h (0.800
      +/- 0.043) (P < 0.05), but it was weaker than non-RNA-interference-groups at each
      time point (P < 0.05). After silencing DAP12 expression in RAW264.7 cells by RNA
      interference, the expressions of Btk, Tec, NFATc1 increased as time passed (6, 12
      h) (P < 0.05), but the expressions on corresponding time decreased sharply
      compared with those in control groups (P < 0.05). CONCLUSIONS: DAP12 pathway play
      an important role in regulating osteoclast differentiation induced by tensile
      strain.

PMID- 23141734
TI  - [Summary of the seventh national conference on the science of dental materials].

PMID- 23141735
TI  - [p53 gene therapy for oral cancer].

PMID- 23141736
TI  - [Research advances in vascularized bone tissue engineering].

PMID- 23141737
TI  - Can sludge dewatering reactivate microorganisms in mesophilically digested
      anaerobic sludge? Case of belt filter versus centrifuge.
AB  - The anaerobic digestion process that successfully reduces the organic content of
      sludge is one of the most common alternatives to meet pathogen reduction
      requirements for particular classes of biosolids. However, recently it was
      reported that, much higher densities of indicator bacteria were measured in
      dewatered cake samples compared to samples collected after anaerobic digestion.
      Additionally, this increase was commonly observed after centrifugation but not
      after belt filter dewatering. Several hypotheses were tested to explain this
      occurrence; however, much of the attention was given to the reactivation of the
      indicator bacteria which might enter a viable but non-culturable state (VBNC)
      during digestion. The objective of this research is to examine sludge samples
      from 5 different full-scale treatment plants in order to observe the effect of
      dewatering processes on the reactivation potential of indicator bacteria. The
      bacterial enumerations were performed by both Standard Culturing Methods (SCM)
      and quantitative polymerase chain (qPCR) on samples collected after digestion and
      dewatering. Results obtained by SCM indicated that in two investigated treatment
      plants operating belt filter dewatering, an average 0.6 log decrease was observed
      after the dewatering process. However, 0.7-1.4 log increases were observed
      immediately after centrifuge dewatering for the other three treatment plants. On
      the other hand, qPCR results gave 0.1-1.9 log higher numbers compared to SCM.
      Comparative evaluation of results obtained by two analytical methods for five
      treatment plants indicates that the differences observed might be originating
      from both reactivation of VBNC bacteria and amplification of DNA from dead cells
      found in the sludge.

PMID- 23141738
TI  - Emergency treatment for zeta chain-associated protein of 70 kDa (ZAP70)
      deficiency.

PMID- 23141739
TI  - Validation of the Cork-Southampton Food Challenge Outcome Calculator in a
      Canadian sample.

PMID- 23141740
TI  - Reduced type I interferon production by dendritic cells and weakened antiviral
      immunity in patients with Wiskott-Aldrich syndrome protein deficiency.
AB  - BACKGROUND: Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary
      immunodeficiency caused by absence of Wiskott-Aldrich syndrome protein (WASP)
      expression, resulting in defective function of many immune cell lineages and
      susceptibility to severe bacterial, viral, and fungal infections. Despite a
      significant proportion of patients with WAS having recurrent viral infections,
      surprisingly little is known about the effects of WASP deficiency on antiviral
      immunity. OBJECTIVE: We sought to evaluate the antiviral immune response in
      patients with WASP deficiency in vivo. METHODS: Viral clearance and associated
      immunopathology were measured after infection of WASP-deficient (WAS KO) mice
      with lymphocytic choriomeningitis virus (LCMV). Induction of antiviral CD8(+) T
      cell immunity and cytotoxicity was documented in WAS KO mice by means of temporal
      enumeration of total and antigen-specific T-cell numbers. Type I interferon (IFN
      I) production was measured in serum in response to LCMV challenge and
      characterized in vivo by using IFN-I reporter mice crossed with WAS KO mice.
      RESULTS: WAS KO mice showed reduced viral clearance and enhanced immunopathology
      during LCMV infection. This was attributed to both an intrinsic CD8(+) T-cell
      defect and defective priming of CD8(+) T cells by dendritic cells (DCs). IFN-I
      production by WAS KO DCs was reduced both in vivo and in vitro. CONCLUSIONS:
      These studies use a well-characterized model of persistence-prone viral infection
      to reveal a critical deficiency of CD8(+) T-cell responses in murine WASP
      deficiency, in which abrogated production of IFN-I by DCs might play an important
      contributory role. These findings might help us to understand the
      immunodeficiency of WAS.

PMID- 23141741
TI  - Kiwifruit allergy across Europe: clinical manifestation and IgE recognition
      patterns to kiwifruit allergens.
AB  - BACKGROUND: Kiwifruit is a common cause of food allergy. Symptoms range from mild
      to anaphylactic reactions. OBJECTIVE: We sought to elucidate geographic
      differences across Europe regarding clinical patterns and sensitization to
      kiwifruit allergens. Factors associated with the severity of kiwifruit allergy
      were identified, and the diagnostic performance of specific kiwifruit allergens
      was investigated. METHODS: This study was part of EuroPrevall, a multicenter
      European study investigating several aspects of food allergy. Three hundred
      eleven patients with kiwifruit allergy from 12 countries representing 4 climatic
      regions were included. Specific IgE to 6 allergens (Act d 1, Act d 2, Act d 5,
      Act d 8, Act d 9, and Act d 10) and kiwifruit extract were tested by using
      ImmunoCAP. RESULTS: Patients from Iceland were mainly sensitized to Act d 1
      (32%), those from western/central and eastern Europe were mainly sensitized to
      Act d 8 (pathogenesis-related class 10 protein, 58% and 44%, respectively), and
      those from southern Europe were mainly sensitized to Act d 9 (profilin, 31%) and
      Act d 10 (nonspecific lipid transfer protein, 22%). Sensitization to Act d 1 and
      living in Iceland were independently and significantly associated with severe
      kiwifruit allergy (odds ratio, 3.98 [P = .003] and 5.60 [P < .001],
      respectively). Using a panel of 6 kiwifruit allergens in ImmunoCAP increased the
      diagnostic sensitivity to 65% compared with 20% for skin prick tests and 46%
      ImmunoCAP using kiwi extract. CONCLUSION: Kiwifruit allergen sensitization
      patterns differ across Europe. The use of specific kiwifruit allergens improved
      the diagnostic performance compared with kiwifruit extract. Sensitization to Act
      d 1 and living in Iceland are strong risk factors for severe kiwifruit allergy.

PMID- 23141742
TI  - Alexithymia and low cooperativeness are associated with suicide attempts in male
      military personnel with adjustment disorder: a case-control study.
AB  - Subpopulations of patients with adjustment disorder are at increased risk for
      suicide. The current study investigated whether personality traits, including
      alexithymia, temperament, and character, are associated with an increased risk of
      suicide in individuals with adjustment disorder. Age- and sex-matched patients
      meeting the diagnostic and statistical manual of mental disorders (DSM-IV)
      criteria for adjustment disorder with (n=92) and without (n=92) a history of
      suicide attempts were recruited for the present study. Ninety-two healthy
      individuals who did not meet diagnostic criteria for Axis I or II diagnoses were
      used as controls. The Toronto alexithymia scale-20 (TAS-20) and the temperament
      and character inventory (TCI) were used to assess personality traits.
      Significantly higher total and subscale scores on the TAS-20, including on the
      difficulty-identifying-feelings (DIF) and difficulty-describing-feelings (DDF)
      subscales, and lower scores on the TCI cooperativeness subscale were noted in
      adjustment-disorder patients with previous suicide attempts. In the multivariate
      regression analysis, high DDF and DIF and low cooperativeness increased the risk
      of suicide attempts in adjustment-disorder patients. A subsequent path analysis
      revealed that high DDF had a direct effect on suicide attempts, whereas high DIF
      had an indirect effect on suicide attempts via low cooperativeness.

PMID- 23141743
TI  - Results of 24 nerve repairs at more than one year post-injury.
AB  - There is no consensus in the literature as to the maximum delay for nerve repair
      following nerve injury. Our aim is to estimate the maximum delay at which a nerve
      can be successfully reconstructed. Eighteen patients (24 procedures) were
      operated at more than 12 months (12 to 36) post-injury. Mean age was 38 (17 to
      74). There were 18 nerve transfers, four grafts and two secondary sutures for six
      target muscles. Evaluation of muscle power was scored and assessed against
      weights starting 12 months follow-up. Finally, two patients had contraction
      against 7 kg, two against 5 kg, six M4. Two were scored M3 and six were M2, thus
      12 good results (67%). This study showed that excellent results could be obtained
      for nerve repair even after 24 months delay. Further study may be needed to
      determine the cut-off point of delay after which nerve recovery is unlikely.

PMID- 23141744
TI  - Gaseous emission during the composting of pig feces from Chinese Ganqinfen
      system.
AB  - The Ganqinfen system - a process of manually cleaning animal feces by means of a
      shovel - is a widely used manure separating method in Chinese pig farms.
      Ganqinfen pig feces and chopped corn stalks were mixed at the ratio of 7:1, and
      composted in 1.5 m(3) rotting boxes for 70 d. Evolution of CH(4), N(2)O and NH(3)
      during composting, and the effects of turning and covering, were studied in this
      research. Results showed that 20-39% and 0.5-4% of total nitrogen were lost in
      the form of NH(3) and N(2)O respectively, and 0.1-0.9% of initial organic carbon
      was emitted as CH(4). Turning enhanced air exchange in the piles, thus decreasing
      CH(4) emission by 83-93% and shortening the maturing period. When trials were
      finished, all non-turned piles were separated to three layers by moisture
      content. This structure caused the N(2)O losses of non-turning treatments to be 6
      12.7 times higher than that of turning treatments. Covering materials reduced air
      exchange at the surface of the pile, thus decreasing the O(2) supply and
      consequently increasing CH(4) production by 33-45%. Covering also reduced NH(3)
      emission by 4-34%. For the composting of Ganqinfen pig feces, we suggest that a
      program of turning twice weekly without covering will result in compost that is
      sufficiently matured after 6 wk with the lowest resultant greenhouse gas
      emission.

PMID- 23141745
TI  - Aroma helps to preserve information processing resources of the brain in healthy
      subjects but not in temporal lobe epilepsy.
AB  - PURPOSE: Inhalation of ylang-ylang aroma has been shown to reduce the auditory
      P300, an event-related potential thought to reflect higher-order processing.
      Because olfactory function is sometimes disturbed in temporal lobe epilepsy
      (TLE), the objective of the present study was to determine whether the effect of
      ylang-ylang aroma on the auditory P300 was impaired in patients with TLE. METHOD:
      Fourteen subjects with TLE and 14 healthy controls participated in this study.
      Electroencephalograms were recorded during an auditory oddball task, and ylang
      ylang aroma or odorless air was delivered through a mask. RESULTS: We found that
      the ylang-ylang aroma prolonged the latencies of P300 in both groups. The ylang
      ylang aroma significantly reduced the P300 amplitudes of healthy subjects as
      described previously. However, in TLE patients, the P300 was unaffected by the
      aroma. CONCLUSION: The current results show that exposure to the ylang-ylang
      aroma reduced information processing resources in healthy subjects but had
      limited effects in patients with TLE. We suggest that impaired higher-order
      olfactory processing in TLE patients may inhibit the effects of the ylang-ylang
      aroma on the P300.

PMID- 23141746
TI  - [Evaluation of the level of stress and his indicators in physicians working in
      operating room].
AB  - METHODS: A questionnaire (146 questions) devised by ASSPRO Scientifique
      (Association de prevention du risque operatoire - Association for the prevention
      of surgical risk) and covering the professional and personal indicators likely to
      be involved in stress was used to assess the level of satisfaction or
      dissatisfaction of physicians and the level of stress. The collected data were
      analysed using frequency distribution tables and cross tabulations. RESULTS: Of
      the completed questionnaires returned by 1272 physicians (21.9% of the sampled
      physicians), 1204 questionnaires could be used. Of the total sample, 85.5% was
      male, between 35 and 64 years old (92.8%); they were anaesthetists (29.6%),
      orthopaedists (29.4%) or obstetrician gynaecologists (12.8%) attending a single
      workplace (67.9%) in sector 2 (64%). More than one quarter of these physicians
      reported feelings of exhaustion after work and one quarter of them had a fear of
      the workload ahead. Overall, the mean level of happiness (on a scale from 0 to
      10) was quite high (6.7) and the mean stress level (graded from 0 to 10) was 5.9
      (above or equal to 8 in 29.8%). The links between the stress level and the
      behaviour or the frame of mind at work were especially clear and significant for
      the following factors (stress level on a scale from 0 to 10): fear of the
      workload ahead (8.3), feeling of exhaustion (7.6), inability to 'switch off'
      (7.5) or to distance oneself from the difficult times of the day (7.3), sleeping
      disturbances (7.3), back pain (6.9) and headaches (6.9), which factors seem to be
      strong indicators of an advanced state of stress.

PMID- 23141747
TI  - CpG oligodeoxynucleotides induce the expression of the antimicrobial peptide
      cathelicidin in glial cells.
AB  - During bacterial infections, antimicrobial peptides are synthesised as an
      important part of the innate immune system. However, expression and function in
      the central nervous system (CNS) need further investigations. The aim of this
      study was to examine the involvement of the pattern-recognition-receptor toll
      like receptor 9 (TLR9) in the expression of the cathelin-related antimicrobial
      peptide (CRAMP) and to characterise the participating signal transduction
      pathways. In primary TLR9 deficient and wildtype mice astrocytes as well as
      microglia cells, the expression of CRAMP after treatment with the TLR9 agonist
      unmethylated cytosine-guanine oligodeoxynucleotide motifs (CpG-DNA) was examined
      in vitro. In vivo CRAMP expression after intraventricular infusion of CpG-DNA in
      TLR9 deficient and wildtype mice as well as in mice with pneumococcal meningitis
      localised in glial cells was determined. Furthermore, the regulation of different
      signal transduction pathways involved in CpG-DNA-induced CRAMP expression in
      glial cells was analysed. An in vitro and in vivo CpG-DNA-induced increase of
      CRAMP expression in astrocytes and microglia cells using real time RT-PCR and
      immunofluorescence was demonstrated. Different signal transduction pathways such
      as mitogen-activated protein kinases and inflammatory mediated pathways are
      involved in the expression of CRAMP in primary glial cells. Interestingly, TLR9
      deficient glial cells showed a reduced but not completely abolished CRAMP mRNA
      expression and ERK1/2 phosphorylation in response to CpG-DNA treatment. On the
      other side in vivo, TLR9 deletion did not change CRAMP expression after bacterial
      infection. In conclusion, our results show that TLR9 can induce the expression of
      antimicrobial peptides such as CRAMP in response to bacterial DNA motifs in
      primary glial cells. Additional findings suggest also that CpG-DNA-induced
      effects are not only mediated by TLR9, but also mediated by other pattern
      recognition receptors.

PMID- 23141748
TI  - Increased IFNalpha activity and differential antibody response in patients with a
      history of Lyme disease and persistent cognitive deficits.
AB  - Following antibiotic treatment for Lyme disease, some patients report persistent
      or relapsing symptoms of pain, fatigue, and/or cognitive deficits. Factors other
      than active infection, including immune abnormalities, have been suggested, but
      few clues regarding mechanism have emerged. Furthermore, the effect of antibiotic
      treatment on immune response in affected individuals remains unknown. In this
      study, a longitudinal analysis of specific immune markers of interest was carried
      out in patients with a history of Lyme disease and persistent objective memory
      impairment, prior to and following treatment with either ceftriaxone or placebo.
      IFNalpha activity was measured by detection of serum-induced changes in specific
      target genes, using a functional cell-based assay and quantitative real-time PCR.
      Level and pattern of antibody reactivity to brain antigens and to Borrelia
      burgdorferi proteins were analyzed by ELISA and immunoblotting. Sera from the
      patient cohort induced significantly higher expression of IFIT1 and IFI44 target
      genes than those from healthy controls, indicating increased IFNalpha activity.
      Antibody reactivity to specific brain and borrelial proteins was significantly
      elevated in affected patients. IFNalpha activity and antibody profile did not
      change significantly in response to ceftriaxone. The heightened antibody response
      implies enhanced immune stimulation, possibly due to prolonged exposure to the
      organism prior to the initial diagnosis and antibiotic treatment of Lyme disease.
      The increase in IFNalpha activity is suggestive of a mechanism contributing to
      the ongoing neuropsychiatric symptoms.

PMID- 23141749
TI  - DIRAE study: seasonal allergic rhinitis distribution in Spain.
AB  - BACKGROUND: National epidemiological study to observe if among patients with
      pollinic seasonal allergic rhinitis (SAR), there are differences between those
      visited by primary care physicians (GPs) or allergists (ALs). METHODS: 758 and
      739 adults were recruited respectively by GPs and ALs. The physicians filled in a
      questionnaire: ARIA classification, prescribed treatment, and asthma incidence.
      The patient completed a visual analogical scale (VAS) to evaluate the severity of
      the rhinitis. Rhinitis control (controlled, partially controlled, and not
      controlled) was assessed by physician and patient. RESULTS: No significant
      differences were found among patients visited by GPs or ALs concerning the ARIA
      classification and rhinitis severity. Treatment with oral antihistamines was
      92.3% and 89.3% for GPs and ALs, respectively. The use of nasal corticosteroids
      was 76.7% and 60.4% for GP and AL patients, respectively. 31.9% of the patients
      visited by the ALs were treated with immunotherapy. The use of alternative
      medicine was 10.9% and 7.6% in GP and AL patients, respectively. The perception
      of "controlled" rhinitis was similar among patients (40.0%) and doctors (40.1%),
      although patients referred differences depending if they were visited by GP
      (44.8%) or AL (34.9%). Asthma prevalence was higher in those who suffered
      persistent as compared to intermittent rhinitis (OR=1.81, 95% CI: 1.39-2.36,
      p<0.001), and moderate/severe vs. mild rhinitis (OR=1.68, 95% CI: 1.05-2.68,
      p=0.029). CONCLUSION: The patients with pollinic SAR visited by GPs or ALs show
      no differences in severity. Less than half of the patients can be considered as
      "controlled".

PMID- 23141750
TI  - Perception of bronchodilation assessed by Visual Analogue Scale in children with
      asthma.
AB  - BACKGROUND: Visual Analogue Scale (VAS) has been proposed as a useful tool for
      assessing the perception of asthma symptoms, a cornerstone in disease management.
      While airway flow limitation and its reversibility are thought to be a useful
      marker of disease severity, there are very few studies that evaluated the
      response to bronchodilation (BD) testing perception by VAS. To investigate
      whether VAS assessment of breathlessness perception could provide a useful tool
      to assess the response to BD testing in asthmatic children. METHODS: This cross
      sectional study included a total of 150 children (96 males, mean age 11.05 years)
      with asthma, 50 had bronchial obstruction (i.e. FEV1 <80% of predicted).
      Perception of breathlessness was assessed by VAS; lung function was measured by
      spirometry. BD testing was performed in all children. RESULTS: In children with
      bronchial obstruction, VAS at baseline was 4.7 and significantly increased to 6.9
      (p<0.001) after BD. In children without bronchial obstruction, VAS at baseline
      was 7.4, but further significantly increased to 8.4 after BD testing (p<0.01).
      There was a significant difference in Delta VAS between children with bronchial
      reversibility and children without it (p<0.0001). CONCLUSIONS: The present study
      demonstrates that VAS might be considered an initial tool to assess the BD
      response in children with asthma, mainly with overt bronchial obstruction.

PMID- 23141751
TI  - Modulation of IgE immunoreactivity to broad bean proteins after food processing
      in a Moroccan population.
AB  - BACKGROUND: The aim of this study was to assess the sensitivity profile of the
      population of Fez and Casablanca in Morocco to dry broad bean (Vicia faba), and
      to investigate the effect of food processing (heat and/or enzymatic hydrolysis by
      pepsin) on the human IgE binding capacity to broad bean proteins (BBP). METHODS:
      Sera samples from 146 patients with atopic hypersensitivity were recruited in
      order to evaluate specific IgE levels to native and processed broad bean proteins
      by ELISA. Under the same conditions, we assessed the immunoreactivity of rabbit
      IgG obtained by immunisation with native BBP. RESULTS: High IgE levels to BBP
      were found; in fact, 79.3% of children and 80.4% of adults had positive values.
      The heat treatment (70 degrees C during 60 min) of dry beans proteins showed
      slight reduction in recognition of these antigens by rabbit IgG (22%) and by
      human IgE (12%). Pepsin hydrolysis decreased rabbit-IgG recognition by 55% in the
      first 30 min of treatment. In contrast, and under the same conditions, pepsin
      increased human-IgE recognition with an average of 143% for all patients.
      However, the combination of the two treatments (heating and pepsin digestion)
      showed a decrease of 16% in BBP recognition for all patients. CONCLUSIONS: This
      study demonstrates a high sensitivity of a Moroccan population to broad bean
      proteins which was resistant to heat and digestion by pepsin.

PMID- 23141752
TI  - Polysensitisation to rubber additives and dyes in shoes and clothes.

PMID- 23141753
TI  - Allergic hypersensitivity to Deflazacort.

PMID- 23141754
TI  - Milk-induced wheezing in children with asthma.
AB  - BACKGROUND: Food allergy has been gaining increasing attention, mostly as causing
      gastrointestinal and cutaneous reactions. Its role in asthma seems to be under
      recognised. OBJECTIVES: This study's aim is to explore the frequency of
      involvement of a common food, namely cow's milk, in childhood asthma. METHODS: 32
      children (5 months to 11 years; median 24 months; mean 34 months) with asthma and
      a suspected history of cow's milk allergy were studied. They underwent skin prick
      testing (SPT) and specific IgE (sIgE) testing to whole cow's milk (WCM), casein,
      alpha-lactalbumin, and beta-lactoglobulin, followed by single-blind oral milk
      challenge. RESULTS: Reactions to milk challenge occurred in 12 (37.5%) including
      wheezing in 5 (41.7%, or 15.6% of the whole group). Children who developed
      wheezing at the time of challenge were younger than those who had negative
      challenge (23.0 months vs. 34.8 months). Challenge was positive in 33.3% of
      subjects who had a positive SPT, and SPT was positive in 50% of challenge
      positive subjects. Regarding sIgE, challenge was positive in 26.7% of sIgE
      positive subjects, and sIgE was positive in 33.3% of challenge positive subjects.
      Skin or serum testing with individual protein fractions did not seem to add
      significant advantage over testing with WCM alone. CONCLUSION: This study shows
      that cow's milk can cause wheezing in children with asthma. Although SPT seemed
      to be more reliable than sIgE testing, both had suboptimal reliability. It is
      worth considering possible milk allergy in children with asthma, particularly
      when poorly controlled in spite of proper routine management.

PMID- 23141755
TI  - Food protein-induced enterocolitis syndrome (FPIES) and well cooked foods: a
      working hypothesis.

PMID- 23141756
TI  - Identification and distribution of Achromobacter species in cystic fibrosis.
AB  - BACKGROUND: We recently described a multilocus sequence typing scheme for
      Achromobacter that identified several novel species in this genus. METHODS: We
      assessed the ability of nrdA sequence analysis to differentiate Achromobacter
      species, including the seven previously named species and 14 recently described
      genogroups. Confirmation of distinctness between groups was confirmed using the k
      parameter. Using this single locus sequence to differentiate species, we analyzed
      Achromobacter isolates obtained from 341 CF patients in the U.S. RESULTS: We
      found that Achromobacter xylosoxidans accounts for 42% of Achromobacter
      infections, while Achromobacter ruhlandii accounted for 23.5% of infections.
      Isolates from 17% of patients were members of the novel genogroup 14. The
      remaining 17.5% of strains belonged to 11 other species/genogroups. CONCLUSION:
      The use of nrdA sequence analysis allows differentiation of the several
      Achromobacter species that can infect persons with CF. Achromobacter species
      other than A. xylosoxidans account for the majority of Achromobacter infection in
      CF patients in the U.S.

PMID- 23141757
TI  - Multispecies biofilms and host responses: "discriminating the trees from the
      forest".
AB  - Periodontal diseases reflect a tissue destructive process of the hard and soft
      tissues of the periodontium that are initiated by the accumulation of
      multispecies bacterial biofilms in the subgingival sulcus. This accumulation, in
      both quantity and quality of bacteria, results in a chronic immunoinflammatory
      response of the host to control this noxious challenge, leading to collateral
      damage of the tissues. As knowledge of the characteristics of the host-bacterial
      interactions in the oral cavity has expanded, new knowledge has become available
      on the complexity of the microbial challenge and the repertoire of host responses
      to this challenge. Recent results from the Human Microbiome Project continue to
      extend the array of taxa, genera, and species of bacteria that inhabit the
      multiple niches in the oral cavity; however, there is rather sparse information
      regarding variations in how host cells discriminate commensal from pathogenic
      species, as well as how the host response is affected by the three-dimensional
      architecture and interbacterial interactions that occur in the oral biofilms.
      This review provides some insights into these processes by including existing
      literature on the biology of nonoral bacterial biofilms, and the more recent
      literature just beginning to document how the oral cavity responds to
      multispecies biofilms.

PMID- 23141758
TI  - Association of lipoprotein subfractions and coronary artery calcium in patient at
      intermediate cardiovascular risk.
AB  - More precise estimation of the atherogenic lipid parameters could improve
      identification of residual risk beyond what is possible using traditional lipid
      risk factors. The aim of the present study was to explore the association between
      advanced analysis of lipoprotein subfractions and the prevalence of coronary
      artery calcium. Consecutive participants at intermediate cardiovascular risk who
      were undergoing computed tomographic assessment of coronary calcium (calcium
      score) were included. Using a validated ultracentrifugation method (the vertical
      autoprofile II test), cholesterol in eluting lipoprotein subfractions [i.e., low-
      (LDL), very-low-, intermediate-, and high-density lipoprotein subclasses,
      lipoprotein (a), and predominant LDL distribution] was directly quantified. A
      total of 410 patients were included (29% women, mean age 57 years), of whom 297
      (72.4%) had coronary artery calcium. LDL pattern B (predominance of small dense
      particles) emerged as an independent predictor of coronary calcium after
      adjustment for traditional risk factors (odds ratio 4.46, 95% confidence interval
      1.19 to 16.7). However, after additional stratification for dyslipidemia, as
      defined by conventional lipid profiling, a statistically significant prediction
      was only retained for high-density lipoprotein subfraction 2 (odds ratio 3.45,
      95% confidence interval 2.03 to 50.1) and "real" LDL (odds ratio 6.10, 95%
      confidence interval 1.26 to 23.41) in the normolipidemia group and for
      lipoprotein (a) (odds ratio 7.81, 95% confidence interval 1.41 to 43.5) in the
      dyslipidemic group. In conclusion, advanced assessment of the lipoprotein
      subfractions [i.e., LDL pattern B, high-density lipoprotein subfraction 2, "real"
      LDL, and lipoprotein (a)] using the vertical autoprofile II test provided
      additional information to that of conventional risk factors on the prevalence of
      coronary artery calcium in patients at intermediate cardiovascular risk.

PMID- 23141759
TI  - Spatial positioning of cell wall-anchored virulence factors in Gram-positive
      bacteria.
AB  - Many virulence factors of Gram-positive bacteria are anchored to the
      peptidoglycan by a sorting signal. While surface display mechanisms are well
      characterized, less is known about the spatial and temporal organization of these
      proteins in the bacterial envelope. This review summarizes recent studies on the
      rod-shaped Listeria monocytogenes, ovococcal Streptococcus pyogenes and spherical
      Staphylococcus aureus bacteria that provide insights into the
      compartmentalization of the surface and distribution of peptidoglycan-anchored
      proteins in space and time. We discuss models that support mechanistic bases for
      localization of proteins at the poles, septum or lateral sites. The results
      indicate that deployment of virulence factors by pathogenic bacteria is a dynamic
      process tightly connected to secretion, cell morphogenesis, cell division rate
      and gene expression levels.

PMID- 23141760
TI  - Regional HTA in Italy: promising or confusing?
AB  - We assessed the actual implementation and achievements of regional HTA in Italy.
      We conducted a web-based analysis (updated until July 2012). Six key elements
      were identified: availability of official documents, existence of a specific
      workgroup, involvement of external organizations, formal funds for HTA,
      publication of HTA reports, and membership of HTA networks. Then, we searched all
      HTA reports retrieved by key words to analyze whether their contents included
      clinical efficacy, economic evaluation, legal issues, ethics and organization.
      Two researchers analyzed the information separately, as a double check. Sixteen
      regions have formally established a structured workgroup inside their
      organizations. Specific funding for HTA activities could be traced in six
      regions, web-available reports only in four. Around 91% of the total reports
      concerned drugs. Contents mostly focused on epidemiological and clinical issues,
      economic evaluation was often restricted to a brief analysis of costs. Only a few
      reports mentioned organizational implications; ethical, legal and social issues
      were lacking. This survey showed a very uneven picture of HTA in the Italian
      regions. As expected, not all the regions were able to perform HTA, probably on
      account of their wide differences in size, tradition and skills in the health
      care field.

PMID- 23141761
TI  - Electrophoretic assembly of organic molecules and composites for electrochemical
      supercapacitors.
AB  - Electrophoretic deposition (EPD) method has been developed for the fabrication of
      1-pyrenebutyric acid (PBH) films from aqueous solutions. The films can be
      deposited at constant voltage or potentiodynamic conditions. The method allowed
      the formation of 0.1-2 MUm thick films, containing needle-shape PBH particles.
      The deposition mechanism involved the electrophoresis, pH decrease at the anode
      surface, charge neutralization and formation of insoluble PBH films. The film
      morphology and shape of the PBH particles are controlled by the pi-pi stacking
      mechanism of the polyaromatic PBH molecules. The important finding was the
      possibility of controlled EPD of multiwalled carbon nanotubes (MWCNTs) using PBH
      as a charging, dispersing and film forming agent. It was found that at low
      voltages or low PBH concentrations the deposits contained mainly MWCNT. The
      increase in the deposition voltage or/and PBH concentration resulted in co
      deposition of MWCNT and needle-shape PBH particles. The new approach to the
      deposition of MWCNT was used for the fabrication of composite MnO(2)-MWCNT films
      for electrodes of electrochemical supercapacitors, which showed a specific
      capacitance of 250 F g(-1). The EPD method developed in this investigation paves
      the way for the deposition of other small organic molecules and composites and
      their applications in new materials and devices, utilizing functional properties
      of the organic molecules, CNT, and other advanced materials.

PMID- 23141762
TI  - Organophilic worm-like ruthenium nanoparticles catalysts by the modification of
      CTAB on montmorillonite supports.
AB  - A supported Ru catalyst was prepared by using cetyltrimethylammonium bromide
      (CTAB) intercalated montmorillonite as the supporting matrix. The as-prepared Ru
      catalyst was subsequently characterized by XRD, XPS, N(2) sorption, TEM, and
      dispersibility measurement. The results showed that the Ru nanoparticles were in
      the modified montmorillonite interlayers, and the morphology of Ru nanoparticle
      was worm-like. Moreover, this supported Ru catalyst could be well dispersed in
      organic solvents such as toluene. The catalyst exhibited high activity and
      selectivity in the hydrogenation of quinoline even without stirring.

PMID- 23141763
TI  - Interaction of alpha-diimine-chromium(III) complexes with non-ionic surfactant
      Triton X-100.
AB  - Using either luminescence intensity or lifetime measurements, we have studied the
      binding interactions of Cr(NN)(3)(3+) (NN=alpha-diimine ligands) with non-ionic
      solutions of surfactant p-(1,1,3,3-tetramethylbutyl)phenoxypoly(ethylene glycol),
      Triton X-100 (TX-100). The titration curves consisted of two curved regions with
      different slopes. This biphasic behavior of lifetime-TX-100 concentration data
      revealed the presence of premicellar aggregates at low TX-100 concentration and
      the formation of normal micelles at high surfactant concentration. The results
      were analyzed with a model that includes binding of Cr(NN)(3)(3+) (probe) to
      small premicellar aggregates and to micelles. There is a good correlation between
      the hydrophobicity of the ligands of Cr(III) complex and the strength of the
      binding of the complexes to the micelles. A comparison with the binding of
      Cr(NN)(3)(3+) to sodium dodecylsulfate (SDS) is discussed.

PMID- 23141764
TI  - Perspectives on emergency department throughput.

PMID- 23141765
TI  - An exploration of factors influencing ambulance and emergency nurses' protocol
      adherence in the Netherlands.
AB  - INTRODUCTION: Adherence to ambulance and ED protocols is often suboptimal.
      Insight into factors influencing adherence is a requisite for improvement of
      adherence. This study aims to gain an in-depth understanding of factors that
      influence ambulance and emergency nurses' adherence to protocols. METHODS: Semi
      structured interviews were held with ambulance nurses, emergency nurses, and
      physicians (N = 20) with medical end responsibility in the Netherlands to explore
      influencing factors. Content analysis was used to identify influencing factors.
      RESULTS: The main influencing factors for adherence were individual factors,
      including individual (clinical) experience, awareness, and the preference of
      following local protocols instead of national protocols. Organizational or
      external factors were involvement in protocol development, training and
      education, control mechanisms for adherence, and physicians' interest. Also of
      influence were protocol characteristics including integration of the advanced
      trauma life support approach, being in accordance with daily practice, and the
      generality of the content. Influencing factors could be a barrier as well as a
      facilitator for adherence. DISCUSSION: Factors influencing ambulance and
      emergency nurses' protocol adherence could be assigned to individual,
      organizational, and external categories, as well as to protocol characteristics.
      To improve adherence, implementation strategies should be tailored to identified
      factors. Multifaceted implementation strategies will be needed to improve
      adherence.

PMID- 23141766
TI  - A rapid screening technique for estimating nanoparticle transport in porous
      media.
AB  - Quantifying the mobility of engineered nanoparticles in hydrologic pathways from
      point of release to human or ecological receptors is essential for assessing
      environmental exposures. Column transport experiments are a widely used technique
      to estimate the transport parameters of engineered nanoparticles in the
      subsurface environment, but this technique is often time-consuming, labor
      intensive, and of low sample throughput. Thus, the traditional column experiment
      is unlikely to be a viable tool for processing the large numbers of engineered
      nanomaterials in various types of porous media that will be needed for
      environmental impact assessment and regulatory activities. Here we present a high
      throughput screening technique for nanoparticle transport using 96 deep well
      plate columns packed with porous media. The technique was tested for the
      transport of 60-nm polystyrene microspheres, fullerene C60 nanoparticles
      (aq/nC60), and surfactant-wrapped single-walled carbon nanotubes (SWNTs) in 0.001
      0.1% sodium dodecyl sulfate (SDS) through Iota quartz sand and Calls Creek
      sediment. Our results showed that this screening technique produced highly
      reproducible column hydrodynamic properties as revealed by conservative tracer
      tests and precise measurements of nanoparticle transport parameters.
      Additionally, all nanoparticles exhibited greater retention in the sediment than
      in Iota quartz, and the retention of SDS-SWNTs decreased with increasing SDS
      concentrations, which is consistent with the existing literature. We conclude
      that this technique is well suited for rapidly screening the mobility of
      engineered nanomaterials in porous media.

PMID- 23141767
TI  - Transport and retention of high concentrated nano-Fe/Cu particles through highly
      flow-rated packed sand column.
AB  - The design of an efficient field-scale remediation based on the use of nanoscale
      zero valent iron (NZVI) requires an accurate assessment of the mobility of such
      particles in saturated porous media, both during injection in the subsurface
      (short-term mobility) and later (long-term mobility). In this study, the mobility
      of highly concentrated dispersions of bimetallic Fe/Cu nanoparticles (d(50) = 70
      +/- 5 nm) in sand-packed columns (0.5 m length and 0.025 m inner diameter) was
      studied. In particular, the influence of flow rate (V = 5 * 10(-4), 1 * 10(-3), 2
      * 10(-3) m/s) and injected particle concentrations (2, 5, 8, 12 g/l) was
      addressed. Breakthrough curves and water pressure drop along the column, averaged
      effective porosity and final distribution of retained particles along the column
      were measured. Experimental results evidenced a good mobility of the Fe/Cu
      particles, with significant breakthrough in all explored experimental conditions
      of flow rate and C(0), without requiring the addition of any stabilizing agent.
      Clogging phenomenon of the column and also the pore pressure variation during
      injection period are strongly affected by injected concentration. Clogging due to
      deposition of particles following a ripening dynamics was observed in particular
      for C(0) = 8 and 12 g/l. The experimental data were modeled using the E-MNM1D
      software. The study has implications for field injection of bimetallic
      nanoparticles, suggesting that particular care is to be devoted when selecting
      injection concentration, to avoid porous medium clogging and control the radius
      of influence.

PMID- 23141768
TI  - Fate and effect of naphthenic acids on oil refinery activated sludge wastewater
      treatment systems.
AB  - Naphthenic acids (NAs) are a complex group of alkyl-substituted acyclic,
      monocyclic and polycyclic carboxylic acids present in oil sands process waters,
      crude oil, refinery wastewater and petroleum products. Crude oil, desalter brine,
      influent, activated sludge mixed liquor and effluent refinery samples were
      received from six United States refineries. The total acid number (TAN) of the
      six crudes tested ranged from 0.12 to 1.5 mg KOH/g crude oil and correlated to
      the total NA concentration in the crudes. The total NA concentration in the
      desalter brine, influent, activated sludge mixed liquor and effluent samples
      ranged from 4.2 to 40.4, 4.5 to 16.6, 9.6 to 140.3 and 2.8 to 11.6 mg NA/L,
      respectively. The NAs in all wastewater streams accounted for less than 16% of
      the total COD, indicating that many other organic compounds are present and that
      NAs are a minor component in refinery wastewaters. Susceptibility tests showed
      that none of the activated sludge heterotrophic microcosms was completely
      inhibited by NAs up to 400 mg/L. Growth inhibition ranging from 10 to 59% was
      observed in all microcosms at and above 100 mg NA/L. NAs chronically-sorbed to
      activated sludge mixed liquor biomass and powdered activated carbon (PAC) were
      recalcitrant and persistent. More than 80% of the total NAs remained in the solid
      phase at the end of the 10-day desorption period (five successive desorption
      steps). Throughout a 90-day incubation period, the total NA concentration
      decreased by 33 and 51% in PAC-free and PAC-containing mixed liquor microcosms,
      respectively. The lower molecular weight fraction of NAs was preferentially
      degraded in both mixed liquors. The persistence of the residual, higher molecular
      weight NAs is likely a combination of molecular recalcitrance and decreased
      bioavailability when chronically-sorbed to the biomass and/or PAC.

PMID- 23141769
TI  - Learning from nature: new approaches to the metabolic engineering of plant
      defense pathways.
AB  - Biotechnological manipulation of plant defense pathways can increase crop
      resistance to herbivores and pathogens while also increasing yields of medicinal,
      industrial, flavor and fragrance compounds. The most successful achievements in
      engineering defense pathways can be attributed to researchers striving to imitate
      natural plant regulatory mechanisms. For example, the introduction of
      transcription factors that control several genes in one pathway is often a
      valuable strategy to increase flux in that pathway. The use of multi-gene
      cassettes which mimic natural gene clusters can facilitate coordinated regulation
      of a pathway and speed transformation efforts. The targeting of defense pathway
      genes to organs and tissues in which the defensive products are typically made
      and stored can also increase yield as well as defensive potential.

PMID- 23141770
TI  - Proteomics approaches for the analysis of enriched microbial subpopulations and
      visualization of complex functional information.
AB  - Advances in the separation of microbial subpopulations and in proteomics
      technologies have paved the way for the global molecular characterization of
      microbial cells that share common functional characteristics. Quantitative
      characterization of the dynamics of microbial proteomes enables an unprecedented
      view of the adaptive responses of microbes to environmental stimuli or during
      interaction with other species or host cells. However, the intrinsic complexity
      of such data requires sophisticated visualization methods for the display,
      mining, interpretation and efficient exploitation of these data resources. In
      this review, we discuss how new approaches in data visualization such as
      streamgraphs, network graphs or Voronoi treemaps are being used in the field to
      provide new insights into the functional complexity of microbial cells,
      populations and multispecies consortia.

PMID- 23141771
TI  - The non-neuronal cholinergic system: basic science, therapeutic implications and
      new perspectives.

PMID- 23141772
TI  - How to explain the unusually late age at skill competence among humans.
AB  - Humans stand out among primates and other mammals in reaching adult-level
      foraging skills very late in development, well after the onset of reproduction.
      The aim of this paper is to place this unusual human skill development into a
      broader comparative context. Among birds and mammals in general, duration of
      immaturity, indexed by age at first reproduction (AFR), and adult brain size have
      undergone correlated evolution. This pattern is consistent with two causal
      processes: AFR is either limited by the time needed to learn adult-level skills
      (needing to learn) or by the energy needed to grow brain and body to full size
      (energetic constraints). We tested predictions arising from these two hypotheses
      with data retrieved from the published literature for 57 mammal and bird species.
      First, most mammals reach adult-level foraging skills well before the
      developmental period is completed, implying that energy constraints determine the
      age at first reproduction, whereas most birds reach adult-level foraging skills
      around the time of maturity, suggesting time needed for skill acquisition
      determines the onset of reproduction. Second, within mammals we found that with
      increasing niche complexity, the age of adult-level skill competence moves closer
      to the age at first reproduction. Third, when looking at how adult-level skills
      can be reached later, we found that gregariousness, slow conservative development
      and post-weaning provisioning allow mammals to reach their skills later. Finally,
      in species with intense sharing of resources (such as cooperative hunters)
      competence in foraging skills may even reach peak values after age of first
      reproduction. We conclude that the human pattern of skill acquisition could arise
      because our hominin ancestors added cooperative breeding and hunting to the slow
      development they had as great apes with increasingly complex niches. This result
      provides a broad biological foundation for the embodied capital model.

PMID- 23141774
TI  - Determination of 2-methylimidazole, 4-methylimidazole and 2-acetyl-4-(1,2,3,4
      tetrahydroxybutyl)imidazole in caramel colours and cola using LC/MS/MS.
AB  - Substituted imidazoles recently came under scrutiny as they may be indirectly
      introduced into cola beverages via the use of class IV (E150d) caramel colours
      and may pose health hazards. A LC/MS/MS method was developed for determining 2-
      and 4-methylimidazole (2-MI, 4-MI) and 2-acetyl-4-(1,2,3,4)
      tetrahydroxybutylimidazole (THI) in beverages and caramel colours. The method is
      very rapid and easy to conduct as it requires only dilution in eluent for sample
      preparation. For 4-MI, the recovery was between 94 and 102% for spiked cola
      samples. The limit of detection was 2MUg/L in the measuring solution
      (corresponding to 40MUg/L for cola samples diluted 1:20 during sample
      preparation). 97 cola samples and 13 caramel colours from Germany and France were
      analysed. From the 3 analytes, only 4-MI was found in the samples with very
      varying concentrations (non quantifiable traces to 0.6mg/L in colas and 175
      658mg/kg in E150d). The exposure for cola drinkers in worst case scenarios is
      estimated to be 2-5MUg/kg bodyweight/day, which is judged as being only a low
      risk for public health.

PMID- 23141775
TI  - A novel p.Leu213X mutation in GJB2 gene in a Portuguese family.
AB  - INTRODUCTION: Hearing loss is the most common sensory disability and is present
      in about 1.9 per 1000 infants at birth. The DFNB1 locus (13q11-q12) includes the
      genes GJB2, coding for connexin 26, and GJB6, encoding connexin 30. More than 100
      mutations have been identified associated with autosomal dominant and recessive
      hearing loss in the GJB2 gene. OBJECTIVES: The aim of the present study was to
      identify the genetic aetiology of deafness in two Portuguese individuals,
      presenting nonsyndromic sensorineural moderate and severe hearing loss,
      respectively. PATIENTS AND METHODS: The individuals were evaluated in both ears
      by pure tone audiometry and blood samples were collected after written informed
      consent was signed. DNA extraction and PCR amplification of GJB2 coding region
      followed standard methodologies. PCR products were automatically sequenced in
      both directions. RESULTS: We identified a novel mutation, c.638T>A (p.Leu213X),
      in GJB2 gene. This nonsense mutation was found in both siblings, and was
      inherited from their hearing father. Molecular analysis showed that the two
      siblings were also heterozygous for c.333-334delAA, a previously described GJB2
      deletion. This novel mutation was not found in a random control sample of 480
      individuals that were screened for coding region of GJB2 gene. p.Leu213X mutation
      identified in this study for the first time changes the codon 213, coding for a
      highly conserved and slowly evolving residue of connexin 26, localised to the C
      terminus domain of the protein, to a STOP codon, leading to the deletion of the
      last 14 amino acids of the protein. CONCLUSION: We can conclude that the
      aetiology of deafness in these individuals is due to the GJB2 genotype involving
      the c.333-334delAA deletion and the novel p.Leu213X mutation in compound
      heterozygosity.

PMID- 23141776
TI  - Neoadjuvant chemotherapy with gemcitabine/cisplatin vs.
      methotrexate/vinblastine/doxorubicin/cisplatin for muscle-invasive urothelial
      carcinoma of the bladder: a retrospective analysis from the University of
      Southern California.
AB  - OBJECTIVES: We evaluated pathologic and survival outcomes of GC
      (gemcitabine/cisplatin) and methotrexate/vinblastine/doxorubicin/cisplatin (M
      VAC) neoadjuvant chemotherapy (NAC) in patients with muscle-invasive bladder
      cancer (MIBC). MATERIALS AND METHODS: A retrospective analysis of prospectively
      collected data on 116 patients who received NAC (GC: n = 58; M-VAC: n = 58)
      before radical cystectomy and superextended pelvic lymph node dissection for
      clinical stage T2-4N0M0 bladder cancer was performed. The outcomes were complete
      response rate (CRR; pT0N0), partial response rate (PRR; pT0N0, pTaN0, pT1N0, or
      pTisN0), overall mortality (OM), and recurrence. The Kaplan-Meier method and
      multivariable Cox regression analysis were used to analyze OM. The cumulative
      incidence method and Fine and Gray's competing risk regression analysis were used
      to analyze recurrence. RESULTS: The median follow-up duration was 2.1 years for
      the GC group and 7.4 years for the M-VAC group (P < 0.001). There were no
      statistically significant differences between the GC and M-VAC groups with regard
      to CRR (27.3% vs. 17.1%, P = 0.419) or PRR (45.5% vs. 37.1%, P = 0.498). The
      predicted 5-year freedom from OM rate (P = 0.634) and cumulative incidence of
      recurrence rate (P = 0.891) did not differ between the GC and M-VAC groups.
      Multivariable analysis showed that there was no independent association between
      type of NAC and OM (P = 0.721) or recurrence (P = 0.065). CONCLUSIONS: Pathologic
      and survival outcomes did not differ in patients who received GC and M-VAC NAC.
      These data support the use of the GC regimen in the neoadjuvant setting.

PMID- 23141777
TI  - The role of lymph vessel density and lymphangiogenesis in metastatic tumor spread
      of nonseminomatous testicular germ cell tumors.
AB  - OBJECTIVES: To evaluate the role of lymph vessel density (LVD) and
      lymphangiogenesis in nonseminomatous testicular germ cell tumors (NSGCT) using
      the specific lymphatic endothelial cell (LEC) marker LYVE-1. MATERIALS AND
      METHODS: NSGCT specimens of 77 patients (32 with and 45 without metastases) were
      stained immunohistochemically using a LYVE-1 antibody. LVD was measured in
      different representative areas by the standardized "hot spot" method.
      Fluorescence double stainings for LYVE-1 and Ki-67 were performed. The median
      follow-up period was 46 (range 3-170) months. RESULTS: The mean peritumoral (2.16
      +/- 2.17) and nontumoral LVD (3.17 +/- 3.24) were significantly higher than
      intratumoral LVD (0.16 +/- 0.73) (both: P = < 0.001). In 5 patients proliferating
      LECs were observed. The peritumoral LVD was 2.66 (+/- 2.31) and 1.80 (+/- 2.02)
      in metastatic and nonmetastatic NSGCT, respectively. A higher peritumoral LVD was
      associated with the presence of metastases at the time of diagnosis (P = 0.087).
      The mean peritumoral LVD in tumors with and without lymphovascular invasion (LVI)
      was 3.33 (+/- 2.20) and 1.62 (+/- 1.95), respectively (P < 0.001). The presence
      of LVI detected by LYVE-1 (LVI-LYVE-1) was independently associated with
      metastatic disease (logistic regression; P = 0.045). CONCLUSIONS: The presence of
      a high peritumoral LVD and LVI-LYVE-1 are both associated with metastatic disease
      in NSGCT. LVI-LYVE-1 was independently associated with the presence of metastases
      at the time of diagnosis. Proliferating LECs are present, suggesting that
      lymphangiogenesis may promote metastatic dissemination of tumor cells in NSGCT.

PMID- 23141778
TI  - Adolescent urologic oncology: current issues and future directions.
AB  - Recent Surveillance Epidemiology and End Results (SEER) data indicate that the
      annual cancer incidence in adolescents is higher than in children, and is on the
      rise. However, the amount of attention, research funding, and therapeutic
      progress made in the adolescent oncology population pales in comparison with that
      of pediatric oncology. Issues of adolescent oncology have only recently been
      acknowledged by leaders in the field, and current efforts now focus on raising
      awareness of this unique patient group. In urology, there have been many gains
      made in pediatric urologic oncology, most notably in Wilms tumor and
      genitourinary rhabdomyosarcoma (genitourinary [GU] rhabdomyosarcoma [RMS]);
      however, there has been little to no progress in the adolescent population. In
      general, adolescent cancer represents the interface between pediatric and adult
      oncology. Similarly, adolescent urologic oncology must be approached as a
      distinct entity because of the unique disease processes, treatment-related
      comorbidities, and psychosocial issues. This article will serve to review the
      most pertinent adolescent urologic oncologic diagnoses (testicular germ call
      malignancy, the second peak of the bimodal age distribution of GU-RMS, and
      adolescent renal malignancies). Also, we focus on such issues as the therapeutic
      impact on fertility, radiation exposure during therapy, and surveillance, risk of
      secondary malignancy, the long-term impact of chemotherapy, and the psychosocial
      burden of cancer in this population. Lastly, we highlight future directions and
      the foreseeable obstacles towards achieving the same research and therapeutic
      success enjoyed in pediatric urologic oncology. 

PMID- 23141779
TI  - Nodal staging score: a tool for survival prediction of node-negative bladder
      cancer.
AB  - PURPOSE: A recently developed nodal staging score (NSS) might give an estimation
      of the likelihood of lymph node (LN) metastasis more accurately than simple
      cutoff of the number of LNs removed. The study aimed to evaluate whether patients
      with higher NSS will have a better outcome, since the NSS may provide an accurate
      staging across tumor stages. MATERIALS AND METHODS: The clinical and
      histopathologic data from 242 patients with LN-negative urothelial bladder cancer
      (pN0) were analyzed. Probability of missing positive LN of <10% (clinical NSS
      90%) was set by examining 6 nodes for clinical Ta-Tis tumors, 9 nodes for cT1
      tumors, and 25 nodes for cT2 tumors. Multivariate analysis by Cox's proportional
      hazards model was used to determine the contribution of NSS to cancer-specific
      survival rates of patients. Discrimination, calibration, and clinical net benefit
      of the Cox regression model were evaluated using a time-dependent receiver
      operating characteristics curve, plotting Kaplan-Meyer curve and decision curve
      analysis. RESULTS: Margin status and NSS exhibited independent contributions in
      the Cox regression model. The predictive accuracy of the Cox regression model was
      0.756. The Cox regression model successfully stratified the outcome into three
      different groups based on score. At 2, 5, and 8 years, the Cox regression model
      performed well across a wide range of threshold probabilities using decision
      curve analysis. CONCLUSIONS: Our findings support the prognostic relevance of the
      NSS 90% cutoff in patients with LN-negative bladder cancer. The present results
      should be validated by prospective studies with defined LN dissection area.

PMID- 23141780
TI  - Carbonic anhydrase IX as a potential biomarker of efficacy in metastatic clear
      cell renal cell carcinoma patients receiving sorafenib or placebo: analysis from
      the treatment approaches in renal cancer global evaluation trial (TARGET).
AB  - OBJECTIVE: Retrospective data analyses have suggested that carbonic anhydrase IX
      (CAIX) may have a predictive role in patients with metastatic clear cell renal
      cell carcinoma (ccRCC) receiving high dose interleukin-2 or sorafenib. We
      examined the predictive value of CAIX in estimating treatment outcome in patients
      receiving sorafenib vs. placebo as part of the Treatment Approaches in Renal
      Cancer Global Evaluation Trial (TARGET) study. MATERIALS AND METHODS: Paraffin
      embedded tumor tissues were collected from 133 patients from the TARGET study (n
      = 903). The percentage of CAIX-positive cells was assessed by a single
      pathologist. The impact of CAIX expression on progression-free survival (PFS,
      primary endpoint) and tumor shrinkage (TS, secondary endpoint) was analyzed.
      RESULTS: Clinical characteristics were similarly distributed between patients
      with low vs. high CAIX staining, as well as patients with available CAIX data vs.
      not. Median PFS for patients with high CAIX vs. low CAIX expression was 5.5 and
      5.4 months, respectively, on the sorafenib arm (P = 0.97), and 1.5 and 1.7 months
      on the placebo arm (P = 0.76). Median TS for patients with high CAIX status was 
      14.9% vs. -12.6% in patients with low CAIX status (P = 0.63) on the sorafenib
      arm, and +1.3% (high CAIX) vs. +4.8% (low CAIX) in patients on the placebo arm (P
      = 0.60). CONCLUSIONS: Despite suggestive retrospective evidence, data from the
      TARGET study did not find CAIX expression status to be either predictive of
      clinical benefit for treatment with sorafenib or of prognostic value in patients
      with metastatic ccRCC following cytokine therapy.

PMID- 23141781
TI  - Genetic analysis of the principal genes related to prostate cancer: a review.
AB  - Prostate cancer is one of the most common leading causes of cancer death in men.
      Attributable to many genetic linkage and genome-wide association studies (GWAS)
      around the world, several high-penetrance genetic variants have been identified.
      Many polymorphisms in genes, such as ELAC2 (locus HPC2), RNase L (locus
      hereditary prostate cancer 1 gene [HPC1]), and MSR1 have been recognized as
      important genetic factors that confer an increased risk of developing prostate
      cancer in many populations. A review of the literature was then performed
      analyzing the roles of these and other genes in prostate cancer. Our main
      challenge is optimizing the role of these genes in prostate cancer development,
      even trying to use these genes as general biomarkers. The principal aim of this
      review is to determine the most important variants in the principal genes related
      to prostate cancer and examine the differences among populations. The concept of
      individualized or personalized targeted cancer therapy has gained significant
      attention throughout oncology. In prostate cancer, the creation of a personalized
      panel of single-nucleotide polymorphisms (SNP) biomarkers may be important for
      the early and accurate detection of this cancer. As a result, the need for a good
      biomarker is required to detect prostate cancer earlier and to provide tools to
      follow patients during the early stages of the cancer. At present, prostate
      cancer continues to have an unclear etiology, which is a combination of genetic
      and numerous environmental factors. Among genetic factors, no variants of the
      RNase L, ELAC2, or MSR1 genes have been detected with similar expression patterns
      in different populations all around the world. 

PMID- 23141782
TI  - How reliable are "reputable sources" for medical information on the Internet? The
      case of hormonal therapy to treat prostate cancer.
AB  - OBJECTIVES: Prostate cancer patients, as well as their caregivers and healthcare
      providers, often search the Internet for information about treatment options. We
      aimed to assess how accurate and up-to-date information about prostate cancer
      treatments is on websites owned and managed by health-related organizations that
      most patients and health care providers would consider to be the most
      trustworthy, based on the reputations of the site providers. MATERIALS AND
      METHODS: We reviewed 43 noncommercial and easily found websites that offered
      extensive information on treatment options for prostate cancer patients. To
      assess how comprehensive the sites were, we focused on the information they
      provided on alternative hormonal therapies to commonly prescribed luteinizing
      hormone-releasing hormone (LHRH) agonists, namely GnRH antagonists and parenteral
      estradiol. RESULTS: Only 14 of 43 websites presented GnRH antagonists as a
      therapy option for prostate cancer. Sixteen of these 43 websites presented
      estrogen as a possible treatment option, but only 1 of the 43 websites contained
      current information on parenteral estrogen treatments. Less than half of the
      sites provided time stamps indicating when they were last updated. Furthermore,
      most sites with time stamps were not in fact up-to-date based on the information
      posted on the site. CONCLUSIONS: Few seemingly reputable Internet sources for
      medical information provide viewers with the detailed and up-to-date information
      that they may expect from such sites when searching for alternatives to standard
      treatment for androgen suppression. Strategies for keeping such websites up-to
      date and reliable are discussed. Sites may improve their credibility and
      usefulness if they (1) present all evidence-based treatment options, (2)
      regularly update and time stamp their information, (3) acknowledge that their
      recommendations on treatments may become out-of-date quickly, (4) and direct
      viewers to information on relevant, active clinical trials. Maintaining high
      quality sites may ultimately depend on users taking the initiative to inform
      website owners when their sites are out-of-date.

PMID- 23141783
TI  - Urine cell-free DNA integrity as a marker for early bladder cancer diagnosis:
      preliminary data.
AB  - OBJECTIVES: Urine cell-free (UCF) DNA has recently been proposed as a potential
      marker for early bladder cancer diagnosis. It is known that normal apoptotic
      cells produce highly fragmented DNA while cancer cells release longer DNA.
      Therefore, we verified the potential role of UCF DNA integrity in early bladder
      cancer diagnosis. MATERIALS AND METHODS: UCF DNA was isolated from 51 bladder
      cancer patients, 46 symptomatic patients, and 32 healthy volunteers. To verify
      UCF DNA integrity, sequences longer than 250 bp, c-Myc, BCAS1, and HER2, were
      quantified by real time PCR. RESULTS: At the best cutoff value of 0.1 ng/MUl, UCF
      DNA integrity analysis showed a sensitivity of 0.73 (95% CI 0.61-0.85), and a
      specificity of 0.84 (95% CI 0.71-0.97) in healthy individuals and 0.83 (95% CI
      0.72-0.94) in symptomatic patients. Receiver operating characteristic (ROC) curve
      analysis revealed an area under the curve of 0.834 (95% CI 0.739-0.930) for
      healthy individuals and 0.796 (95% CI 0.707-0.885) for symptomatic patients.
      CONCLUSIONS: These preliminary data suggest that UCF DNA integrity is a
      potentially good marker for early noninvasive diagnosis of bladder cancer. Its
      diagnostic performance does not seem to vary significantly, even in an "at risk"
      population of symptomatic individuals.

PMID- 23141784
TI  - [Prevalence of hypertension in Portuguese adolescents in Lisbon, Portugal].
AB  - AIMS: To determine the prevalence of pre-hypertension (pre-HTN) and hypertension
      (HTN) in Portuguese adolescents in Lisbon and to ascertain the relationship
      between blood pressure (BP) levels and the risk factors of gender, obesity,
      smoking, alcohol consumption, exercise and family history of HTN. METHODS: This
      was a cross-sectional study in a non-randomized sample of 234 adolescents of both
      sexes, aged between 16 and 19 years. Information on habits and family history of
      HTN was obtained through a self-completed structured questionnaire. RESULTS: The
      study included 234 adolescents, mean age 16.4+/-0.9 years, 57% male. The
      prevalence of HTN was 34%, higher in males (44% vs. 21%, p=0.001) and 12% of pre
      HTN, higher in females (13% vs. 10%, p=0.001). Higher body mass index was
      associated with significantly higher prevalence of pre-HTN (normal weight 9.40%,
      overweight 16.10%, and obesity 22.70%) and HTN (normal weight 30.4%, overweight
      45.2%, and obesity 45.5%). With a family history of HTN, the prevalence of HTN
      and pre-HTN was approximately double (41% vs. 28% and 18% vs. 9%, respectively).
      Regular exercise, smoking and alcohol consumption were not significantly
      associated with BP values. CONCLUSION: The prevalence of pre-HTN and HTN in the
      sample studied was high. Of the risk factors evaluated, only gender, obesity and
      family history of HTN were significantly associated with BP values.

PMID- 23141785
TI  - [Percutaneous thrombus aspiration in renal artery stenosis after renal
      transplantation].
AB  - We describe the case of a patient with chronic renal failure under hemodialysis
      for five years who, after renal transplantation, developed acute renal failure
      and hypertension refractory to medical therapy. Given the clinical and imaging
      (renal ultrasound and computed tomography) suspicion of renal artery graft
      thrombosis, invasive angiography was performed, which confirmed the diagnosis.
      The therapeutic approach consisted of percutaneous thrombus aspiration and
      subsequent balloon angioplasty of the entire artery, followed by stent
      implantation in a second procedure. The clinical course was uneventful with
      improvement of renal function and normalization of blood pressure. The case
      highlights the importance of percutaneous intervention in the management of
      patients with vascular complications after transplantation, with successful
      application of a procedure normally used in the setting of acute myocardial
      infarction - percutaneous thrombus aspiration and implantation of a drug-eluting
      vascular stent.

PMID- 23141786
TI  - The brain as filter: on removing the stuffing from the keyhole.

PMID- 23141787
TI  - Meaning as a healing agent.

PMID- 23141788
TI  - Nonlocality, near-death experiences, and the challenge of consciousness.

PMID- 23141789
TI  - Thought Field Therapy (TFT) as a treatment for anxiety symptoms: a randomized
      controlled trial.
AB  - OBJECTIVE: To investigate whether thought field therapy (TFT) has an impact on
      anxiety symptoms in patients with a variety of anxiety disorders. DESIGN: Forty
      five patients were randomized to either TFT (n = 23) or a waiting list (n = 22)
      condition. The wait-list group was reassessed and compared with the TFT group two
      and a half months after the initial evaluation. After the reassessment, the wait
      list patients received treatment with TFT. All 45 patients were followed up one
      to two weeks after TFT treatment, as well as at three and 12 months after
      treatment. SUBJECTS: Patients with an anxiety disorder, mostly outpatients.
      INTERVENTION: TFT aims to influence the body's bioenergy field by tapping on
      specific points along energy meridians, thereby relieving anxiety and other
      symptoms. OUTCOME MEASURES: Symptom Checklist 90-Revised, Hospital Anxiety and
      Depression Scale, the Sheehan Disability Scale. RESULTS: Repeated-measures
      analysis of variance was used to compare the TFT and the wait-list group. The TFT
      group had a significantly better outcome on two measures of anxiety and one
      measure of function. Follow-up data for all patients taken together showed a
      significant decrease in all symptoms during the one to two weeks between the
      pretreatment and the post-treatment assessments. The significant improvement seen
      after treatment was maintained at the three- and 12-month assessments.
      CONCLUSIONS: The results suggest that TFT may have an enduring anxiety-reducing
      effect.

PMID- 23141790
TI  - Entangled in the womb? A pilot study on the possible physiological connectedness
      between identical twins with different embryonic backgrounds.
AB  - OBJECTIVE: Studies of synchronous physiological responses to startle stimuli
      between monozygotic twins and other paired subjects have suffered from
      methodological flaws such as post-hoc specifications of "connectedness" criteria.
      The mechanisms that affect any such connectedness are unknown. With the logistic
      and financial support of a television company, we conducted a methodological
      pilot study with predefined objective hit criteria in which we used four pairs of
      twins with frequent experiences of connectedness. METHODS: While one twin was
      exposed during a 12-minute period to five randomly presented mild shock or
      surprise stimuli, the electrodermal activity, blood pressure, breathing, and
      bodily movements were simultaneously recorded in the second twin. An authorized
      polygraph expert who was blind to the stimulus exposure times examined the data
      for deviations from normal physiological patterns during relaxation and delivered
      precisely timed estimates of such deviations. "Hits" (indications of
      connectedness) were objectively defined as an estimate lying within a 15-second
      "hit window." RESULTS: Overall results were nonsignificant, P > .7. However, for
      one pair of twins, the polygraph expert identified 10 deviating patterns, of
      which three were hits were P < .03. This data set was sent to a second,
      independent expert, who blindly identified the same three hits, pointing to only
      eight patterns, P < .0003. DISCUSSION: We argue that the applied methodology for
      "hit" identification is objective and recommendable. Speculatively, because the
      "successful" pair of twins was reported to be monochorionic-monoamnionic (as
      embryos, they shared the same placenta and the same bag of water), embryonic
      history might be further investigated as a potential factor for connectedness
      between monozygotic twins.

PMID- 23141791
TI  - Patients seek integrative medicine for preventive approach to optimize health.
AB  - CONTEXT: Despite the tremendous growth of integrative medicine (IM) in clinical
      settings, IM has not been well characterized in the medical literature.
      OBJECTIVE: To describe characteristics and motivation of patients seeking care at
      an IM clinic. DESIGN, SETTING, AND PARTICIPANTS: Patients from a nine-site
      practice-based research network participated in this cross-sectional survey.
      Clinicians documented patients' medical conditions. MAIN OUTCOME MEASURES:
      Patients provided information on demographics, lifestyle factors, and reasons for
      seeking care at an IM center. Clinicians documented the medical condition treated
      and procedures performed at the visit. RESULTS: A total of 4,182 patients (84.5%
      white; 72.7% college-educated; and 73.4% female) reported their most important
      reasons for seeking IM. Top-ranked reasons were (1) "to improve health and
      wellness now to prevent future problems" (83.9%); (2) "to try new options for
      health care" (76.7%); and (3) "to maximize my health regardless of whether or not
      my illness is curable" (74.6%). Interestingly, the same top reasons were reported
      by subgroups of patients who sought IM for wellness, acute care, or chronic
      illness. Patient reports of lifestyle also demonstrated healthier behaviors than
      national samples indicate. Patients seeking clinical care at IM centers desire an
      expanded paradigm of health care, one that seeks to maximize health.

PMID- 23141792
TI  - Energy therapies: focus on spirituality.
AB  - RESEARCH QUESTION: How are spiritual experiences described by participants of an
      energy based healing session? THEORETICAL FRAMEWORK: A taxonomy of spiritual
      experiences (TSE), developed from previous research, provided a linguistic tool
      to explore and describe spiritual experiences. METHODOLOGY: A secondary
      qualitative analysis was conducted on a subset of existing data. CONTEXT:
      Original data was from accounts of spiritual experiences from participants in
      Healing Touch classes. SAMPLE SELECTION AND DATA COLLECTION: A purposive sample
      of accounts of spiritual experiences that occurred during giving or receiving an
      energy based healing session (n=56) was drawn from the existing data base of
      spiritual experience accounts. ANALYSIS AND INTERPRETATION: A top down deductive
      analysis using the TSE as a coding schema was applied to this sample. Comparisons
      were made between this subset who described their spiritual experience
      specifically occurring during a healing session and the original dataset of more
      general descriptions of a spiritual experience. Comparisons were also made
      between this subset and the original data as well as between giving and receiving
      a healing. MAIN RESULTS: The components of the taxonomy were well represented and
      richly described as occurring during a healing session. Notable similarities
      between giving and receiving a healing were apparent in the descriptions of
      sensate experiences, ecstasy, and experiences of encounters with disincarnate
      guides. Healing activities are a rich context for spiritual experiences. The
      taxonomy provides a useful linguistic and cognitive structure for exploring
      spiritual experiences.

PMID- 23141793
TI  - Medical and psychology students' knowledge of and attitudes towards mindfulness
      as a clinical intervention.
AB  - BACKGROUND: Mindfulness is a technique for training people to pay full attention
      and to fully accept the reality of what they are paying attention to. The
      clinical efficacy of mindfulness has been increasingly demonstrated during the
      last two decades. Very little research, however, has been undertaken on health
      professionals' and students of health professions' knowledge of and attitudes
      towards mindfulness. These may affect the current and future level of use of a
      technique that offers important clinical advantages. OBJECTIVES: We aimed to
      compare knowledge of and attitudes towards mindfulness of medical students
      without exposure to it in their training with psychology students without
      exposure and with medical students with exposure to mindfulness in their
      training. METHODS: A total of 91 medical students from Monash University, 49
      medical students from Deakin University, and 31 psychology students from Deakin
      University were given a questionnaire that elicited quantitative and qualitative
      responses about level of knowledge of mindfulness and willingness to administer
      or recommend it to their future patients. RESULTS: Psychology students without
      exposure to mindfulness in their training have a greater knowledge of it and are
      more likely to administer it or recommend it than are medical students without
      exposure to it in their training. Medical students with exposure to mindfulness
      in their course have a greater knowledge of it and are more likely to administer
      it or recommend it than are medical students without exposure. Knowledge of
      mindfulness is positively correlated with students' willingness to use or
      recommend it. CONCLUSIONS: Possible implications of the findings of this study
      are that if future doctors are routinely instructed in mindfulness as a clinical
      intervention they may be more likely to form a more positive attitude towards it,
      that is more consistent with that of nonmedical health professions such as
      psychologists, and that they therefore may be more likely to administer it or
      refer its use. The inclusion of mindfulness exposure in medical courses, and
      possibly also in psychology courses, may help mindfulness fulfill its clinical
      potential, and increasingly benefit patients who are suffering from a range of
      clinical conditions.

PMID- 23141794
TI  - Three principles of integral healthcare.

PMID- 23141796
TI  - Interprofessional student education: exchange program between Albert Einstein
      College of Medicine and Pacific College of Oriental Medicine.
AB  - The growing popularity of complementary and alternative medicine (CAM), of which
      estimated 38% of adults in the United States used in 2007, has engendered changes
      in medical school curricula to increase students' awareness of it. Exchange
      programs between conventional medical schools and CAM institutions are recognized
      as an effective method of interprofessional education. The exchange program
      between Albert Einstein College of Medicine (Einstein, Yeshiva University) and
      Pacific College of Oriental Medicine, New York campus (PCOM-NY) is in its fifth
      year and is part of a broader relationship between the schools encompassing
      research, clinical training, interinstitutional faculty and board appointments,
      and several educational activities. The Einstein/PCOM-NY student education
      exchange program is part of the Einstein Introduction to Clinical Medicine
      Program and involves students from Einstein learning about Chinese medicine
      through a lecture, the experience of having acupuncture, and a four-hour
      preceptorship at the PCOM outpatient clinic. The students from PCOM learn about
      allopathic medicine training through an orientation lecture, a two-and-a-half
      hour dissection laboratory session along side Einstein student hosts, and a tour
      of the clinical skills center at the Einstein campus. In the 2011/2012 offering
      of the exchange program, the participating Einstein and PCOM students were
      surveyed to assess the educational outcomes. The data indicate that the exchange
      program was highly valued by all students and provided a unique learning
      experience. Survey responses from the Einstein students indicated the need for
      greater emphasis on referral information, which has been highlighted in the
      literature as an important medical curriculum integrative medicine competency.

PMID- 23141797
TI  - Assessment of knowledge about cervical cancer and its prevention among female
      students aged 17-26 years.
AB  - OBJECTIVE: To assess knowledge about cervical cancer and its primary and
      secondary prevention, and identify the sources of information about the disease
      among female high school and university students in Krakow, Poland. STUDY DESIGN:
      This study was based on a questionnaire consisting of 64 questions, divided into
      six parts: personal data, general knowledge about cervical cancer, estimation of
      risk factors, knowledge about primary prevention, knowledge about secondary
      prevention, and information sources. Data were collected from students aged 17-26
      years over a 3-month period in 2011 and 2012. RESULTS: Four hundred women living
      in Krakow or its vicinity were included in the study. Nearly all respondents
      (98.5%) had heard of cervical cancer, 89.4% were aware of the risk of death
      associated with cervical cancer, and 44.8% believed that the disease could affect
      them in the future. The interviewees considered genetics and family history to be
      the most important risk factors, followed by infection with human papillomavirus
      (HPV) and having multiple sex partners. Most (91.5%) respondents had not been
      vaccinated against HPV, 47.9% did not know where to go to get vaccinated, and
      30.1% were unaware of vaccination as a prevention method. Most (91.5%)
      respondents were aware of cytological screening, and 86.5% thought that they
      should have it done in the future. Women who had not heard of cytological
      screening were more likely to be unaware of cervical cancer than women who had
      heard about cytological screening (odds ratio 0.24, 95% confidence interval 0.11
      0.49, p=0.0001). The Internet, television and newspapers were reported to be the
      main sources of information about the disease. CONCLUSIONS: General awareness of
      cervical cancer among young women in Poland is insufficient. HPV infection is not
      considered to be the major aetiological factor. A relatively high percentage of
      women in this study had never heard of the HPV vaccine as a way of preventing
      cervical cancer. Knowledge about cytological screening, however, appears to be
      much better.

PMID- 23141798
TI  - Cancer, epigenetics and the Nobel Prizes.

PMID- 23141799
TI  - HDAC inhibitor-based therapies: can we interpret the code?
AB  - Abnormal epigenetic control is a common early event in tumour progression, and
      aberrant acetylation in particular has been implicated in tumourigenesis. One of
      the most promising approaches towards drugs that modulate epigenetic processes
      has been seen in the development of inhibitors of histone deacetylases (HDACs).
      HDACs regulate the acetylation of histones in nucleosomes, which mediates changes
      in chromatin conformation, leading to regulation of gene expression. HDACs also
      regulate the acetylation status of a variety of other non-histone substrates,
      including key tumour suppressor proteins and oncogenes. Histone deacetylase
      inhibitors (HDIs) are potent anti-proliferative agents which modulate acetylation
      by targeting histone deacetylases. Interest is increasing in HDI-based therapies
      and so far, two HDIs, vorinostat (SAHA) and romidepsin (FK228), have been
      approved for treating cutaneous T-cell lymphoma (CTCL). Others are undergoing
      clinical trials. Treatment with HDIs prompts tumour cells to undergo apoptosis,
      and cell-based studies have shown a number of other outcomes to result from HDI
      treatment, including cell-cycle arrest, cell differentiation, anti-angiogenesis
      and autophagy. However, our understanding of the key pathways through which HDAC
      inhibitors affect tumour cell growth remains incomplete, which has hampered
      progress in identifying malignancies other than CTCL which are likely to respond
      to HDI treatment.

PMID- 23141801
TI  - Endoscopic-assisted sphincter pharyngoplasty (EASP).
AB  - OBJECTIVES: Sphincter pharyngoplasty operation was designed for the treatment of
      velopharyngeal insufficiency via a transoral route. Few investigators used
      palatal stretching sutures or palatal splitting procedures (which may affect the
      performance of the palate) to overcome the problem of difficult visualization.
      The purpose of this study is to present and evaluate the role of intraoperative
      nasoendoscopy during sphincter pharyngoplasty. Although Vadodaria et al. (2004)
      (in a cadaver study) used the endoscope to perform SP operation, this study (to
      our knowledge) is the first report of intraoperative nasoendoscopy in sphincter
      pharyngoplasty. SUBJECTS AND METHODS: This prospective study was conducted at ORL
      HN Department, Zagazig University Hospitals, Zagazig University, Egypt. Seven
      patients with persistent postoperative hypernasality were enrolled in this work.
      They were prepared by head and neck physical examination and phonetic evaluation.
      Patients were subjected to treatment by endoscopic-assisted sphincter
      pharyngoplasty, a procedure that was designed to combine both a transoral and a
      transnasal routes via the aid of nasoendoscope. Postoperative nasoendoscopic and
      phonetic assessment was done for all of the patients. RESULTS: The procedure is
      easily conducted, done by available instruments with no extra burden over
      patients or hospitals. The procedure insured an under vision and well controlled
      steps. No major complications were recorded. Good speech outcome results were
      reported. CONCLUSION: Endoscopic-assisted sphincter pharyngoplasty is a new role
      the nasoendoscopy can play. The study demonstrates the feasibility of endoscopic
      assistance in sphincter pharyngoplasty, with the advantage of improved
      visualization of a traditionally difficult-to-expose area. There was neither
      increased risk to the patients nor added cost to the procedure since only widely
      available instrumentation was used. The technique lessened the need for palatal
      stretching or splitting during the procedure.

PMID- 23141802
TI  - Language understanding and vocabulary of early cochlear implanted children.
AB  - OBJECTIVES: The aim of the study was to identify factors associated with the
      level of language understanding, the level of receptive and active vocabulary,
      and to estimate effect-related odds ratios for cochlear implanted children's
      language level. METHODS: The patient material included all children born in
      Denmark between January 2005 and January 2011, having received a cochlear implant
      (CI) and with a minimum of 6 months of hearing with their CI (N=94). The
      participation rate was 88% (N=83). Sixty-eight (82%) of the participating
      children were implanted bilaterally. Mean age at implantation was 19.6 months.
      The mean age at test was 46.3 months and the mean age of hearing with CI was 25.9
      months. The children were tested with three different tests, the PPVT-4, the
      Reynell receptive part and a Danish test "Viborgmaterialet" for active
      vocabulary. Logistic regression models were used for analysis of the potential
      influence of eighteen different factors upon the test outcomes. RESULTS: The
      majority of children did not have age equivalent language understanding and
      vocabulary. There was significant effect of the following factors upon the test
      outcomes: age at hearing aid start before implantation, age at implantation,
      length of hearing, communication mode, mode of implantation, amount of support
      teaching, residence and educational placement. Children who started HA treatment
      before 6 months of age, were implanted before 12 months or did not use total
      communication had the highest odds of having age equivalent language
      understanding and vocabulary. CONCLUSIONS: The majority of hearing impaired
      children in Denmark received hearing aids before six months of hearing and the
      majority was implanted before 18 months of age. Despite these medical and
      technical advances the vast majority did not have age equivalent language
      understanding and vocabulary. Data suggest that the language gap is not closed in
      two years after implantation.

PMID- 23141800
TI  - Epigenetic alterations involved in cancer stem cell reprogramming.
AB  - Current hypotheses suggest that tumors originate from cells that carry out a
      process of "malignant reprogramming" driven by genetic and epigenetic
      alterations. Multiples studies reported the existence of stem-cell-like cells
      that acquire the ability to self-renew and are able to generate the bulk of more
      differentiated cells that form the tumor. This population of cancer cells, called
      cancer stem cells (CSC), is responsible for sustaining the tumor growth and,
      under determined conditions, can disseminate and migrate to give rise to
      secondary tumors or metastases to distant organs. Furthermore, CSCs have shown to
      be more resistant to anti-tumor treatments than the non-stem cancer cells,
      suggesting that surviving CSCs could be responsible for tumor relapse after
      therapy. These important properties have raised the interest in understanding the
      mechanisms that govern the generation and maintenance of this special population
      of cells, considered to lie behind the on/off switches of gene expression
      patterns. In this review, we summarize the most relevant epigenetic alterations,
      from DNA methylation and histone modifications to the recently discovered miRNAs
      that contribute to the regulation of cancer stem cell features in tumor
      progression, metastasis and response to chemotherapy.

PMID- 23141803
TI  - Digenic inheritance in autosomal recessive non-syndromic hearing loss cases
      carrying GJB2 heterozygote mutations: assessment of GJB4, GJA1, and GJC3.
AB  - OBJECTIVE: Autosomal recessive non-syndromic hearing loss (ARNSHL) can be caused
      by many genes. However, mutations in the GJB2 gene, which encodes the gap
      junction (GJ) protein connexin (Cx) 26, constitute a considerable proportion
      differing among population. Between 10 and 42 percent of patients with recessive
      GJB2 mutations carry only one mutant allele. Mutations in GJB4, GJA1, and GJC3
      encoding Cx30.3, Cx43, and Cx29, respectively, can lead to HL. Combination of
      different connexins in heteromeric and heterotypic GJ assemblies is possible.
      This study aims to determine whether variations in any of the genes GJB4, GJA1 or
      GJC3 can be the second mutant allele causing the disease in the digenic mode of
      inheritance in the studied GJB2 heterozygous cases. METHODS: We examined 34
      unrelated GJB2 heterozygous ARNSHL subjects from different geographic and ethnic
      areas in Iran, using polymerase chain reaction (PCR) followed by direct DNA
      sequencing to identify any sequence variations in these genes. Restriction
      fragment length polymorphism (RFLP) assays were performed on 400 normal hearing
      individuals. RESULTS: Sequence analysis of GJB4 showed five heterozygous
      variations including c.451C>A, c.219C>T, c.507C>G, c.155_158delTCTG and c.542C>T,
      with only the latter variation not being detected in any of control samples.
      There were three heterozygous variations including c.758C>T, c.717G>A and
      c.3*dupA in GJA1 in four cases. We found no variations in GJC3 gene sequence.
      CONCLUSION: Our data suggest that GJB4 c.542C>T variant and less likely some
      variations of GJB4 and GJA1, but not possibly GJC3, can be assigned to ARNSHL in
      GJB2 heterozygous mutation carriers providing clues of the digenic pattern.

PMID- 23141804
TI  - Quantitative analysis of multiple fatty acid ethanolamides using ultra
      performance liquid chromatography-tandem mass spectrometry.
AB  - Fatty acid ethanolamides (FAE) represent a group of lipid signaling molecules
      associated with many physiological and pharmacological actions; however, low FAE
      tissue levels pose challenges in terms of analytical characterization. The
      objective was to develop a competent ultra-performance liquid chromatography
      tandem mass spectrometry (UPLC-MS/MS) method for analysis of multiple FAE in
      animal and human tissue samples. Analytes were extracted using lipid-phase and
      solid-phase extraction procedures. Chromatographic separation was achieved using
      a gradient elution in 8 min. FAE were quantified by MS/MS in positive
      electrospray ionization mode. Linearity was shown in lower and higher FAE
      concentration ranges, with a limit of quantification (LOQ) <=0.2 ng/ml for FAE
      including alpha-linolenoylethanolamide (ALEA), arachidonoylethanolamide (AEA),
      docosahexaenoylethanolamide (DHEA), linoleoylethanolamide (LEA),
      oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). Accuracy was shown to
      be between 92.4% and 108.8%, and precision was <10% for all FAE species. In sum,
      this sensitive and reproducible method can be used to simultaneously determine
      multiple FAE at low concentrations in order to facilitate further study of the
      role of FAE on physiological state.

PMID- 23141805
TI  - Surgeons managing conflict in the operating room: defining the educational need
      and identifying effective behaviors.
AB  - BACKGROUND: Developing an operating room conflict management educational program
      for surgeons requires a formal needs assessment and information about behaviors
      that represent effective conflict management. METHODS: Focus groups of
      circulating room nurses and surgeons were conducted at 5 participating centers.
      Participants responded to queries about conflict management training, conflict
      consequences, and effective conflict management behaviors. Transcripts of these
      sessions served as the data for this study. RESULTS: Educational preparation for
      conflict management was inadequate consisting of trial and error with observed
      behaviors. Conflict and conflict mismanagement had negative consequences for team
      members and team performance. Four behaviors emerge as representing effective
      ways for surgeons to manage conflict. CONCLUSIONS: There is a clear educational
      need for conflict management education. Target behaviors have now been identified
      that can provide the basis for a theoretically grounded and contextually adapted
      instruction and assessment of surgeon conflict management.

PMID- 23141806
TI  - Nicotinic acetylcholine receptors containing the alpha4 subunit modulate alcohol
      reward.
AB  - BACKGROUND: Nicotine and alcohol are the two most co-abused drugs in the world,
      suggesting a common mechanism of action might underlie their rewarding
      properties. Although nicotine elicits reward by activating ventral tegmental area
      dopaminergic (DAergic) neurons via high-affinity neuronal nicotinic acetylcholine
      receptors (nAChRs), the mechanism by which alcohol activates these neurons is
      unclear. METHODS: Because most high-affinity nAChRs expressed in ventral
      tegmental area DAergic neurons contain the alpha4 subunit, we measured ethanol
      induced activation of DAergic neurons in midbrain slices from two complementary
      mouse models, an alpha4 knock-out (KO) mouse line and a knock-in line (Leu9'Ala)
      expressing alpha4 subunit-containing nAChRs hypersensitive to agonist compared
      with wild-type (WT). Activation of DAergic neurons by ethanol was analyzed with
      both biophysical and immunohistochemical approaches in midbrain slices. The
      ability of alcohol to condition a place preference in each mouse model was also
      measured. RESULTS: At intoxicating concentrations, ethanol activation of DAergic
      neurons was significantly reduced in alpha4 KO mice compared with WT. Conversely,
      in Leu9'Ala mice, DAergic neurons were activated by low ethanol concentrations
      that did not increase activity of WT neurons. In addition, alcohol potentiated
      the response to ACh in DAergic neurons, an effect reduced in alpha4 KO mice.
      Rewarding alcohol doses failed to condition a place preference in alpha4 KO mice,
      paralleling alcohol effects on DAergic neuron activity, whereas a sub-rewarding
      alcohol dose was sufficient to condition a place preference in Leu9'Ala mice.
      CONCLUSIONS: Together, these data indicate that nAChRs containing the alpha4
      subunit modulate alcohol reward.

PMID- 23141807
TI  - EPR spectroscopy as a tool for investigation of differences in radical status in
      wheat plants of various tolerances to osmotic stress induced by NaCl and PEG
      treatment.
AB  - Two kinds of wheat genotypes with different tolerance to osmotic stress (NaCl and
      PEG-treatment) were investigated with biochemical analyses, including the
      measurements of total antioxidant capacity, 1,1-diphenyl-2-picrylhydrazyl (DPPH)
      radical-scavenging activity, reducing power and starch content. The results were
      compared with electron paramagnetic resonance (EPR) data concerning the nature
      and amounts of stable long lived radicals present in the control and stressed
      plants. In addition, the changes in manganese content upon stress conditions were
      monitored. Different mechanisms of protection against PEG stress in sensitive and
      tolerant wheat genotypes were postulated. In sensitive genotypes, electrons were
      created in excess in stress conditions, and were stabilized by polysaccharide
      molecules, whereas in tolerant genotypes, protection by antioxidants dominated.
      Moreover, the quinone-semiquinone balance shifted towards semiquinone, which
      became the place of electron trapping. NaCl-treatment yielded significant effects
      mainly in sensitive genotypes and was connected with the changes of water
      structure, leading to inactivation of reactive oxygen species by water molecules.

PMID- 23141808
TI  - Genetic pathways in disorders of epidermal differentiation.
AB  - More than 100 human genetic skin diseases, impacting over 20% of the population,
      are characterized by disrupted epidermal differentiation. A significant
      proportion of the 90 genes identified in these disorders to date are concentrated
      within several functional pathways, suggesting the emergence of organizing themes
      in epidermal differentiation. Among these are the Notch, transforming growth
      factor beta (TGFbeta), IkappaB kinase (IKK), Ras/mitogen-activated protein kinase
      (MAPK), phosphoinositide 3-kinase (PI3K), p63, and Wnt signaling pathways, as
      well as core biological processes mediating calcium homeostasis, tissue
      integrity, cornification, and lipid biogenesis. Here, we review recent results
      supporting the central role of these pathways in epidermal differentiation,
      highlighting the integration of genetic information with functional studies to
      illuminate the biological actions of these pathways in humans as well as to guide
      development of future therapeutics to correct their dysfunction.

PMID- 23141809
TI  - Increased plantar force and impulse in American football players with high arch
      compared to normal arch.
AB  - BACKGROUND: Risk of overuse injury among athletes is high due in part to repeated
      loading of the lower extremities. Compared to individuals with normal arch (NA)
      structure, those with high (HA) or low arch (LA) may be at increased risk of
      specific overuse injuries, including stress fractures. A high medial longitudinal
      arch may result in decreased shock absorbing properties due to increased rigidity
      in foot mechanics. While the effect of arch structure on dynamic function has
      been examined in straight line walking and running, the relationship between the
      two during multi-directional movements remains unstudied. OBJECTIVE: The purpose
      of this study was to determine if differences in plantar loading in football
      players occur during both walking and pivoting movements. METHOD: Plantar loading
      was examined in 9 regions of the foot for 26 participants (16 NA, 10 HA).
      RESULTS: High arch athletes demonstrated increased maximum force in the lateral
      rear foot and medial forefoot, and force time integral in the medial forefoot
      while walking. HA athletes also demonstrated increased maximum force in the
      medial rear foot and medial and central forefoot during rapid pivoting.
      CONCLUSIONS: The current findings demonstrate that loading patterns differ
      between football players with high and normal arch structure, which could
      possibly influence injury risk in this population.

PMID- 23141810
TI  - Into the future: diversifying lipid management.

PMID- 23141811
TI  - Comparing diabetes drugs--helping clinical decisions?

PMID- 23141812
TI  - Efficacy, safety, and tolerability of a monoclonal antibody to proprotein
      convertase subtilisin/kexin type 9 as monotherapy in patients with
      hypercholesterolaemia (MENDEL): a randomised, double-blind, placebo-controlled,
      phase 2 study.
AB  - BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) increases serum
      LDL-cholesterol (LDL-C) concentrations. We assessed the effects of AMG 145, a
      human monoclonal antibody against PCSK9, in patients with hypercholesterolaemia
      in the absence of concurrent lipid-lowering treatment. METHODS: In a phase 2
      trial done at 52 centres in Europe, the USA, Canada, and Australia, patients
      (aged 18-75 years) with serum LDL-C concentrations of 2.6 mmol/L or greater but
      less than 4.9 mmol/L were randomly assigned equally through an interactive voice
      response system to subcutaneous injections of AMG 145 70 mg, 105 mg, or 140 mg,
      or placebo every 2 weeks; subcutaneous AMG 145 280 mg, 350 mg, or 420 mg or
      placebo every 4 weeks; or oral ezetimibe 10 mg/day. The primary endpoint was
      percentage change from baseline in LDL-C concentration at week 12. Analysis was
      by modified intention to treat. Study personnel and patients were masked to
      treatment assignment of AMG 145 or placebo. Ezetimibe assignment was open label.
      This trial is registered with ClinicalTrials.gov, number NCT01375777. FINDINGS:
      406 patients were assigned to AMG 145 70 mg (n=45), 105 mg (n=46), or 140 mg
      (n=45) every 2 weeks; AMG 145 280 mg (n=45), 350 mg (n=45), or 420 mg (n=45)
      every 4 weeks; placebo every 2 weeks (n=45) or every 4 weeks (n=45); or ezetimibe
      (n=45). AMG 145 significantly reduced LDL-C concentrations in all dose groups
      (mean baseline LDL-C concentration 3.7 mmol/L [SD 0.6]; changes from baseline
      with every 2 weeks AMG 145 70 mg -41.0% [95% CI -46.2 to -35.8]; 105 mg -43.9% [
      49.0 to -38.7]; 140 mg -50.9% [-56.2 to -45.7]; every 4 weeks AMG 145 280 mg 
      39.0% [-44.1 to -34.0]; 350 mg -43.2% [-48.3 to -38.1]; 420 mg -48.0% [-53.1 to 
      42.9]; placebo every 2 weeks -3.7% [-9.0 to 1.6]; placebo every 4 weeks 4.5% [
      0.7 to 9.8]; and ezetimibe -14.7% [-18.6 to -10.8]; p<0.0001 for all doses vs
      placebo or ezetimibe). Treatment-emergent adverse events occurred in 136 (50%) of
      271 patients in the AMG 145 groups, 41 (46%) of 90 patients in the placebo
      groups, and 26 (58%) of 45 patients in the ezetimibe group; no deaths or serious
      treatment-related adverse events were reported. INTERPRETATION: The results of
      our study support the further assessment of AMG 145 in long-term studies with
      larger and more diverse populations including patients with documented statin
      intolerance. FUNDING: Amgen.

PMID- 23141813
TI  - Efficacy, safety, and tolerability of a monoclonal antibody to proprotein
      convertase subtilisin/kexin type 9 in combination with a statin in patients with
      hypercholesterolaemia (LAPLACE-TIMI 57): a randomised, placebo-controlled, dose
      ranging, phase 2 study.
AB  - BACKGROUND: LDL cholesterol (LDL-C) is a well established risk factor for
      cardiovascular disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9)
      binds LDL receptors, targeting them for degradation. We therefore assessed the
      efficacy, safety, and tolerability of AMG 145, a human monoclonal IgG2 antibody
      against PCSK9, in stable patients with hypercholesterolemia on a statin. METHODS:
      In a phase 2, dose-ranging study done in 78 centres in the USA, Canada, Denmark,
      Hungary, and Czech Republic, patients (aged 18-80 years) with LDL-C greater than
      2.2 mmol/L on a stable dose of statin (with or without ezetimibe), were randomly
      assigned equally, through an interactive voice response system, to subcutaneous
      injections of AMG 145 70 mg, 105 mg, or 140 mg, or matching placebo every 2
      weeks; or subcutaneous injections of AMG 145 280 mg, 350 mg, or 420 mg, or
      matching placebo every 4 weeks. Everyone was masked to treatment assignment
      within the every 2 weeks and every 4 weeks schedules. The primary endpoint was
      the percentage change in LDL-C concentration from baseline after 12 weeks.
      Analysis was by modified intention to treat. This study is registered with
      ClinicalTrials.gov, number NCT01380730. FINDINGS: 631 patients with
      hypercholesterolaemia were randomly assigned to AMG 145 70 mg (n=79), 105 mg
      (n=79), or 140 mg (n=78), or matching placebo (n=78) every 2 weeks; or AMG 145
      280 mg (n=79), 350 mg (n=79), and 420 mg (n=80), and matching placebo (n=79)
      every 4 weeks. At the end of the dosing interval at week 12, the mean LDL-C
      concentrations were reduced generally dose dependently by AMG 145 every 2 weeks
      (ranging from 41.8% to 66.1%; p<0.0001 for each dose vs placebo) and AMG 145
      every 4 weeks (ranging from 41.8% to 50.3%; p<0.0001). No treatment-related
      serious adverse events occurred. The frequencies of treatment-related adverse
      events were similar in the AMG 145 and placebo groups (39 [8%] of 474 vs 11 [7%]
      of 155); none of these events were severe or life-threatening. INTERPRETATION:
      The results suggest that PCSK9 inhibition could be a new model in lipid
      management. Inhibition of PCSK9 warrants assessment in phase 3 clinical trials.
      FUNDING: Amgen.

PMID- 23141814
TI  - Increase in state suicide rates in the USA during economic recession.

PMID- 23141815
TI  - RELAX-AHF: rising from the doldrums in acute heart failure.

PMID- 23141816
TI  - Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure
      (RELAX-AHF): a randomised, placebo-controlled trial.
AB  - BACKGROUND: Serelaxin, recombinant human relaxin-2, is a vasoactive peptide
      hormone with many biological and haemodynamic effects. In a pilot study,
      serelaxin was safe and well tolerated with positive clinical outcome signals in
      patients with acute heart failure. The RELAX-AHF trial tested the hypothesis that
      serelaxin-treated patients would have greater dyspnoea relief compared with
      patients treated with standard care and placebo. METHODS: RELAX-AHF was an
      international, double-blind, placebo-controlled trial, enrolling patients
      admitted to hospital for acute heart failure who were randomly assigned (1:1) via
      a central randomisation scheme blocked by study centre to standard care plus 48-h
      intravenous infusions of placebo or serelaxin (30 MUg/kg per day) within 16 h
      from presentation. All patients had dyspnoea, congestion on chest radiograph,
      increased brain natriuretic peptide (BNP) or N-terminal prohormone of BNP, mild
      to-moderate renal insufficiency, and systolic blood pressure greater than 125 mm
      Hg. Patients, personnel administering study drug, and those undertaking study
      related assessments were masked to treatment assignment. The primary endpoints
      evaluating dyspnoea improvement were change from baseline in the visual analogue
      scale area under the curve (VAS AUC) to day 5 and the proportion of patients with
      moderate or marked dyspnoea improvement measured by Likert scale during the first
      24 h, both analysed by intention to treat. This trial is registered at
      ClinicalTrials.gov, NCT00520806. FINDINGS: 1161 patients were randomly assigned
      to serelaxin (n=581) or placebo (n=580). Serelaxin improved the VAS AUC primary
      dyspnoea endpoint (448 mm * h, 95% CI 120-775; p=0.007) compared with placebo,
      but had no significant effect on the other primary endpoint (Likert scale;
      placebo, 150 patients [26%]; serelaxin, 156 [27%]; p=0.70). No significant
      effects were recorded for the secondary endpoints of cardiovascular death or
      readmission to hospital for heart failure or renal failure (placebo, 75 events
      [60-day Kaplan-Meier estimate, 13.0%]; serelaxin, 76 events [13.2%]; hazard ratio
      [HR] 1.02 [0.74-1.41], p=0.89] or days alive out of the hospital up to day 60
      (placebo, 47.7 [SD 12.1] days; serelaxin, 48.3 [11.6]; p=0.37). Serelaxin
      treatment was associated with significant reductions of other prespecified
      additional endpoints, including fewer deaths at day 180 (placebo, 65 deaths;
      serelaxin, 42; HR 0.63, 95% CI 0.42-0.93; p=0.019). INTERPRETATION: Treatment of
      acute heart failure with serelaxin was associated with dyspnoea relief and
      improvement in other clinical outcomes, but had no effect on readmission to
      hospital. Serelaxin treatment was well tolerated and safe, supported by the
      reduced 180-day mortality. FUNDING: Corthera, a Novartis affiliate company.

PMID- 23141817
TI  - Exenatide once weekly versus liraglutide once daily in patients with type 2
      diabetes (DURATION-6): a randomised, open-label study.
AB  - BACKGROUND: Glucagon-like peptide-1 receptor agonists exenatide and liraglutide
      have been shown to improve glycaemic control and reduce bodyweight in patients
      with type 2 diabetes. We compared the efficacy and safety of exenatide once
      weekly with liraglutide once daily in patients with type 2 diabetes. METHODS: We
      did a 26 week, open-label, randomised, parallel-group study at 105 sites in 19
      countries between Jan 11, 2010, and Jan 17, 2011. Patients aged 18 years or older
      with type 2 diabetes treated with lifestyle modification and oral
      antihyperglycaemic drugs were randomly assigned (1:1), via a computer-generated
      randomisation sequence with a voice response system, to receive injections of
      once-daily liraglutide (1.8 mg) or once-weekly exenatide (2 mg). Participants and
      investigators were not masked to treatment assignment. The primary endpoint was
      change in glycated haemoglobin (HbA(1c)) from baseline to week 26. Analysis was
      by intention to treat. This trial is registered with ClinicalTrials.gov, number
      NCT01029886. FINDINGS: Of 912 randomised patients, 911 were included in the
      intention-to-treat analysis (450 liraglutide, 461 exenatide). The least-squares
      mean change in HbA(1c) was greater in patients in the liraglutide group (-1.48%,
      SE 0.05; n=386) than in those in the exenatide group (-1.28%, 0.05; 390) with the
      treatment difference (0.21%, 95% CI 0.08-0.33) not meeting predefined non
      inferiority criteria (upper limit of CI <0.25%). The most common adverse events
      were nausea (93 [21%] in the liraglutide group vs 43 [9%] in the exenatide
      group), diarrhoea (59 [13%] vs 28 [6%]), and vomiting 48 [11%] vs 17 [4%]), which
      occurred less frequently in the exenatide group and with decreasing incidence
      over time in both groups. 24 (5%) patients allocated to liraglutide and 12 (3%)
      allocated to exenatide discontinued participation because of adverse events.
      INTERPRETATION: Both once daily liraglutide and once weekly exenatide led to
      improvements in glycaemic control, with greater reductions noted with
      liraglutide. These findings, plus differences in injection frequency and
      tolerability, could inform therapeutic decisions for treatment of patients with
      type 2 diabetes. FUNDING: Eli Lilly and Company and Amylin Pharmaceuticals LLC.

PMID- 23141819
TI  - Herd-level risk factors for lameness in freestall farms in the northeastern
      United States and California.
AB  - The objective was to investigate the association between herd-level management
      and facility design factors and the prevalence of lameness in high-producing
      dairy cows in freestall herds in the northeastern United States (NE; Vermont, New
      York, Pennsylvania) and California (CA). Housing and management measures such as
      pen space, stall design, bedding type, and milking routine were collected for the
      high-producing pen in 40 farms in NE and 39 farms in CA. All cows in the pen were
      gait scored using a 1-to-5 scale and classified as clinically lame (score >=3) or
      severely lame (score >=4). Measures associated with the (logit-transformed)
      proportion of clinically or severely lame cows at the univariable level were
      submitted to multivariable general linear models. In NE, lameness increased on
      farms that used sawdust bedding [odds ratio (OR)=1.71; 95% confidence interval
      (CI)=1.06-2.76] and decreased with herd size (OR=0.94; CI=0.90-0.97, for a 100
      cow increase), use of deep bedding (OR=0.48; CI=0.29-0.79), and access to pasture
      (OR=0.52; CI=0.32-0.85). The multivariable model included herd size, access to
      pasture, and provision of deep bedding, and explained 50% of the variation in
      clinical lameness. Severe lameness increased with the percentage of stalls with
      fecal contamination (OR=1.15; CI=1.06-1.25, for a 10% increase) and with use of
      sawdust bedding (OR=2.13; CI=1.31-3.47), and decreased with use of deep bedding
      (OR=0.31; CI=0.19-0.50), sand bedding (OR=0.32; CI=0.19-0.53), herd size
      (OR=0.93; CI=-0.89-0.97, for a 100-cow increase), and rearing replacement heifers
      on site (OR=0.57; CI=0.32-0.99). The multivariable model included deep bedding
      and herd size, and explained 59% of the variation of severe lameness. In CA,
      clinical lameness increased with the percentage of stalls containing fecal
      contamination (OR=1.15; CI=1.05-1.26, for a 10% increase), and decreased with
      herd size (OR=0.96; CI=0.94-0.99, for a 100-cow increase), presence of rubber in
      the alley to the milking parlor (OR=0.46; CI=0.28-0.76), distance of the neck
      rail from the rear curb (OR=0.97; CI=0.95-0.99, for a 1-cm increase), water space
      per cow (OR=0.92; CI=0.85-0.99, for a 1-cm increase), and increased frequency of
      footbaths per week (OR=0.90; CI=081-0.99, for a 1-unit increase). The
      multivariable model included herd size, percentage of stalls containing fecal
      contamination, and presence of rubber in the alley to the milking parlor, and
      explained 44% of the variation of clinical lameness. Severe lameness increased
      with the percentage of stalls containing fecal contamination (OR=1.23; CI=1.06
      1.42, for a 10% increase) and decreased with frequency of manure removal in the
      pen per day (OR=0.72; CI=0.53-0.97, for a 1-unit increase). The final model
      included both variables and explained 28% of the variation in severe lameness. In
      conclusion, changes in housing and management may help decrease the prevalence of
      lameness on dairy farms, but key risk factors vary across regions.

PMID- 23141818
TI  - [Epidemiology of rotavirus gastroenteritis among children under 5 years of age in
      Tunisia - results of sentinel hospital surveillance 2009 to 2011].
AB  - BACKGROUND: Rotavirus is the major cause of severe acute gastroenteritis among
      young children. The objectives of this study were to assess the epidemiology,
      clinical and virological features of community-acquired rotavirus acute
      gastroenteritis, in children under 5 years of age, hospitalized in Tunisia.
      METHODS: A multicenter prospective observational study was conducted from April
      2009 to March 2011, in 11 sentinel pediatric departments. Clinical data and stool
      samples were collected for all children under 5 years, admitted for acute
      gastroenteritis. Rotavirus was detected by Elisa immunoassay test and genotyped
      for G and P by semi-nested multiplex RT-PCR. RESULT: A total of 621 children were
      enrolled in this study. Rotavirus was detected in 30.3% of cases (95% CI [26.7
      33.9]). The estimated incidence rate of rotavirus acute gastroenteritis was 11
      cases/100,000 child-years (95% CI [9.43-12.57]). This infection affected
      predominantly children aged under 24 months, and occurred mainly in winter
      (55.3%). Vomiting, fever and dehydration were observed in 79.6%, 69.5% and 57%
      respectively. Genotype analysis identified four G types (G1, G2, G3 and G4) and 4
      P types (P[4], P[6], P[8] and P[9]). The most common G/P combination was G3P[8]
      (24.4%), followed by G4P[8] (13.3%) and G1P[8] (6.5%). CONCLUSION: These results
      highlight the frequency and potential severity of rotavirus acute gastroenteritis
      in pediatric hospital settings. The present study could provide a sufficient
      database to make a decision related to the introduction of rotavirus vaccine in
      Tunisian national immunization program.

PMID- 23141820
TI  - In vitro degradation of lysine by ruminal fluid-based fermentations and by
      Fusobacterium necrophorum.
AB  - The objective of these studies was to characterize some factors affecting lysine
      degradation by mixed ruminal bacteria and by ruminal Fusobacterium necrophorum.
      Mixed ruminal bacteria degraded lysine, and addition of pure cultures of F.
      necrophorum did not increase lysine degradation. Addition of acetic or propionic
      acid strikingly reduced NH(3) production from lysine by mixed ruminal bacteria at
      pH 6, but not at pH 7. Although typical ruminal environments with acidic pH and
      normal concentrations of volatile fatty acids might inhibit lysine degradation by
      F. necrophorum, ruminal fluid contained enough bacteria with a lysine-degrading
      capacity to ferment 50 mM lysine in vitro. Of 7 strains of ruminal F. necrophorum
      tested, all grew on both lactate and lysine as the primary energy source. Both
      subspecies of ruminal F. necrophorum (necrophorum and funduliforme) used lysine
      as a primary C and energy source. Lysine and glutamic acid were effectively
      fermented by F. necrophorum, but alanine and tryptophan were not, and histidine
      and methionine were fermented only to a minor extent. The end products of lactate
      fermentation by F. necrophorum were propionate and acetate, and those of lysine
      degradation were butyrate and acetate. Fermentation of glutamic acid by F.
      necrophorum yielded acetate and butyrate in a ratio near to 2:1. The minimum
      inhibitory concentration of tylosin for F. necrophorum was not dependent on
      whether bacteria were grown with lactate or lysine, but F. necrophorum was more
      susceptible to monensin when grown on lysine than on lactate. Although F.
      necrophorum is generally resistant to monensin, the ionophore may reduce lysine
      degradation by F. necrophorum in the rumen. The essential oil components
      limonene, at 20 or 100 MUg/mL, and thymol, at 100 MUg/mL, inhibited F.
      necrophorum growth, whereas eugenol, guaiacol, and vanillin had no effect. Our
      findings may lead to ways to minimize ruminal lysine degradation and thus
      increase its availability to the animal.

PMID- 23141821
TI  - Microbiological assessment and evaluation of rehydration instructions on powdered
      infant formulas, follow-up formulas, and infant foods in Malaysia.
AB  - A total of 90 samples comprising powdered infant formulas (n=51), follow-up
      formulas (n=21), and infant foods (n=18) from 15 domestic and imported brands
      were purchased from various retailers in Klang Valley, Malaysia and evaluated in
      terms of microbiological quality and the similarity of rehydration instructions
      on the product label to guidelines set by the World Health Organization.
      Microbiological analysis included the determination of aerobic plate count (APC)
      and the presence of Enterobacteriaceae and Cronobacter spp. Isolates of interest
      were identified using ID 32E (bioMerieux France, Craponne, France). In this
      study, 87% of powdered infant formulas, follow-up formulas, and infant foods
      analyzed had an APC below the permitted level of <10(4) cfu/g. These acceptable
      APC ranged between <10(2) to 7.2*10(3) cfu/g. The most frequently isolated
      Enterobacteriaceae was Enterobacter cloacae, which was present in 3 infant
      formulas and 1 infant food tested. Other Enterobacteriaceae detected from
      powdered infant and follow-up formulas were Citrobacter spp., Klebsiella spp.,
      and other Enterobacter spp. No Cronobacter species were found in any samples.
      Rehydration instructions from the product labels were collated and it was
      observed that none directed the use of water with a temperature >70 degrees C for
      formula preparation, as specified by the 2008 revised World Health Organization
      guidelines. Six brands instructed the use of water at 40 to 55 degrees C, a
      temperature range that would support the survival and even growth of
      Enterobacteriaceae.

PMID- 23141822
TI  - Energy partitioning in herbage-fed dairy cows offered supplementary grain during
      an extended lactation.
AB  - An experiment was conducted to quantify the changes in energy partitioning
      resulting from grain supplementation in herbage-fed dairy cows at 4 stages during
      a 670-d lactation. The experiment used 16 lactating Holstein-Friesian cows, with
      a control and a grain treatment being randomly allocated to 8 cows each. During 4
      measurement periods (each of 4d in a metabolism stall and 3d in an indirect
      calorimeter) beginning at approximately 110, 270, 450, and 560 d in milk (DIM),
      the energy balance of each cow was measured. Cows in both groups were
      individually offered freshly cut ryegrass pasture (Lolium hybridum L.) in periods
      1 and 3 and ryegrass pasture silage and alfalfa (Medicago sativa L.) hay in
      periods 2 and 4. In all periods, cows in the grain group were offered an
      additional 4.4 to 5.0 kg of dry matter of cereal grain/cow per day. Adding grain
      to the diet increased yields of fat and protein and tended to increase yields of
      milk and lactose, but did not affect milk composition. Gross energy intake (GEI)
      declined as lactation progressed. Adding grain to the diet decreased the
      percentage of GEI in feces and urine, but the extent of these reductions did not
      change as lactation progressed. Adding grain to the diet similarly reduced the
      percentage of GEI lost to heat, but again the extent of the reduction remained
      similar as lactation progressed. The magnitude of the increase in milk energy
      resulting from grain supplementation did not change with advancing lactation, but
      tissue energy retention was greater in the first 300 DIM compared with after 300
      DIM. For herbage-based diets, CH(4) emissions ranged from 6.2 to 7.6% of GEI,
      which corresponds to 24.0 to 25.8 g of CH(4)/kg of dry matter intake. For diets
      supplemented with cereal grains, CH(4) emissions ranged from 6.3 to 7.3% of GEI,
      which corresponds to 21.6 to 25.2 g of CH(4)/kg of dry matter intake. It was
      concluded that, for cows producing <24 kg of milk/d and consuming herbage-based
      diets supplemented with grain, the efficiency of utilizing the additional energy
      in the grain, as measured by the loss of energy in heat, and its partitioning to
      milk, did not change as lactation progressed from 110 to 560 DIM.

PMID- 23141823
TI  - Genetic analysis of rennet coagulation time, curd-firming rate, and curd firmness
      assessed over an extended testing period using mechanical and near-infrared
      instruments.
AB  - The aims of this study were (1) to analyze rennet coagulation time (RCT), curd
      firming rate, and curd firmness obtained by extending the standard 30-min testing
      time to 45 min; (2) to estimate heritabilities of the aforementioned traits
      determined by mechanical (Formagraph; Foss Electric, Hillerod, Denmark) and near
      infrared optical (Optigraph; Ysebaert, Frepillon, France) instruments, and to
      assess the statistical relevance of their genetic background by using the Bayes
      factor procedure, the deviance information criterion, and the mean squared error;
      (3) to estimate phenotypic and genetic relationships between instruments within
      trait and between traits within instrument; and (4) to obtain correlations for
      sire rankings based on the used instruments. Individual milk samples were
      collected from 913 Brown Swiss cows reared in 63 herds located in Trento Province
      (Italy). Milk coagulation properties (MCP) were measured using 2 different
      instruments: Formagraph and Optigraph. Both instruments were housed in the same
      laboratory and operated by the same technician. Each sample was analyzed
      simultaneously on each instrument. All experimental conditions (milk temperature
      and the concentration and type of rennet) were identical. For the analysis,
      univariate and bivariate animal models were implemented using Bayesian methods.
      Univariate analyses were conducted to test the hypothesis that the traits showed
      additive genetic determination. Deviance information criterion, Bayes factor, and
      mean squared error were used as model choice criteria. The main results were that
      (1) RCT could be measured on all samples by extending the observation time to 45
      min, and its genetic parameters (h(2)=0.23) and breeding values could be
      estimated while avoiding the bias of noncoagulating samples; (2) curd-firming
      rate could be measured on almost all milk samples, and its genetic parameters
      could be estimated for the first time on a field data set (h(2)=0.21); (3) for
      the first time, genetic parameters of curd firmness 45 min after rennet addition
      (h(2)=0.12) were estimated, and they were compared with curd firmness 30 min
      after rennet addition (h(2)=0.17); and (4) MCP estimated using the Optigraph
      appeared to be genetically different from those determined by Formagraph, with
      the partial exception of RCT (genetic correlation=0.97). Breeding strategies for
      the improvement of MCP must be planned with caution. Currently, the high
      throughput, ease of use, and reduced costs of analysis make predictions obtained
      from mid-infrared spectroscopy (MIRS) on untreated milk samples a promising
      alternative to produce relevant data at the population level. The use of
      mechanical lactodynamographs to establish reference data for MIRS calibrations
      have been already studied, whereas the use of near-infrared optical
      lactodynamographs as a reference method for MIRS calibrations needs to be
      investigated.

PMID- 23141824
TI  - Abundance of adiponectin system and G-protein coupled receptor GPR109A mRNA in
      adipose tissue and liver of F2 offspring cows of Charolais * German Holstein
      crosses that differ in body fat accumulation.
AB  - In addition to its role in energy storage, adipose tissue (AT) is an important
      endocrine organ and it secretes adipokines. The adipokine adiponectin improves
      insulin sensitivity by activation of its receptors AdipoR1 and AdipoR2. Lipolysis
      in AT is downregulated by the G-protein coupled receptor (GPR109A), which binds
      the endogenous ligand beta-hydroxybutyrate (BHBA). Insulin sensitivity is reduced
      during the transition from late pregnancy to early lactation in dairy cattle and
      BHBA is increased postpartum, implying the involvement of the adiponectin system
      and GPR109A in this process. The aim of the current investigation was to study
      the effect of the genetic background of cows on the mRNA abundance of the
      adiponectin system, as well as GPR109A, in an F(2) population of 2 Charolais *
      German Holstein families. These families were deduced from full- and half-sibs
      sharing identical but reciprocal paternal and maternal Charolais grandfathers.
      The animals of the 2 families showed significant differences in fat accretion and
      milk secretion and were designated fat-type (high fat accretion but low milk
      production) and lean-type (low fat accretion but high milk production). The mRNA
      of the adiponectin system and GPR109A were quantified by real-time PCR in
      different fat depots (subcutaneous from back, mesenteric, kidney) and liver. The
      mRNA data were correlated with AT masses (intermuscular topside border fat,
      kidney, mesenteric, omental, total inner fat mass, total subcutaneous fat mass,
      and total fat mass) and blood parameters (glucose, nonesterified fatty acids,
      BHBA, urea, insulin, and glucagon). The abundance of adiponectin system mRNA was
      higher in discrete AT depots of fat-type cows [adiponectin mRNA in mesenteric fat
      (trend), AdipoR1 in kidney and mesenteric AT, and AdipoR2 in subcutaneous fat
      (trend)] than in lean-type cows. More GPR109A mRNA was found in kidney fat of the
      lean-type family than in that of the fat-type family. In liver, the abundance of
      AdipoR2 and GPR109A (trend) mRNA was higher in lean-type than in fat-type cows.
      Correlation analyses disclosed clear differences between the groups. In total,
      the results revealed obvious disparities for the mRNA targets between the 2
      families with common but reciprocal paternal and maternal genetic backgrounds.
      Visceral AT mass of both families showed most correlations with the mRNA
      abundance of the target genes in different AT depots. The effect of adiponectin
      secretion, especially by visceral AT depots, on liver metabolism should be
      clarified in further studies.

PMID- 23141825
TI  - Reproduction in grazing dairy cows treated with 14-day controlled internal drug
      release for presynchronization before timed artificial insemination compared with
      artificial insemination after observed estrus.
AB  - Progesterone-releasing (controlled internal drug release, CIDR) devices inserted
      for 14 d are used to presynchronize the estrous cycle for timed artificial
      insemination (TAI) in beef heifers (14-d CIDR-PGF(2alpha) program). The objective
      was to test a similar program in dairy cows by measuring first-service conception
      rates (FSCR), pregnancy rates after 2 AI, and time to pregnancy compared with a
      control (AI after observed estrus). Postpartum cows (Holstein, Jersey, or
      crossbred; n=1,363) from 4 grazing dairy farms were assigned to 1 of 2 programs:
      14dCIDR_TAI [CIDR in for 14 d, CIDR out, PGF(2alpha) injection at 19 d after CIDR
      removal, GnRH injection 56 h later, and then TAI 16 h later; n=737] or control
      [AI after observed estrus; reproductive program with PGF(2alpha) (cycling cows)
      and CIDR (noncycling cows) to synchronize estrus with the start of the breeding
      season; n=626]. Body condition was scored (1 to 5; thin to fat) at the start of
      the trial. The interval from the start of the breeding period (final PGF(2alpha)
      injection of either program) to first AI was shorter for 14dCIDR_TAI compared
      with the control (3.0+/-0.2 vs. 5.3+/-0.2 d; mean +/- SEM) but 14dCIDR_TAI cows
      had lesser FSCR than controls (48 vs. 61%). Farm affected FSCR (50, 51, 67, and
      58% for farms 1 to 4). The BCS affected FSCR (50, 55, and 62% for BCS=2, 2.5, and
      3, respectively). Cows that either calved the year before (carryover) or that
      calved early in the calving season had greater FSCR than cows that calved later
      in the calving season (55, 61, and 42%, respectively). The percentage of cows
      pregnant to AI (first and second inseminations within 31-d breeding season) was
      similar for 14dCIDR_TAI and control (64 vs. 70%) cows, but farm (64, 62, 80, and
      69%) and time of calving (70, 76, and 56%: carryover, early, and late,
      respectively) affected the percentage. Survival analyses showed an initial
      advantage for 14dCIDR_TAI (more cows inseminated and more pregnancies achieved
      early in the breeding season) that was not maintained over time. Conclusions were
      that the 14dCIDR_TAI program achieved acceptable FSCR (48%) and overall AI
      pregnancy rates (64%), but did not surpass a control program that used AI after
      observed estrus (61 and 70%, respectively).

PMID- 23141826
TI  - Gram-typing of mastitis bacteria in milk samples using flow cytometry.
AB  - Fast identification of pathogenic bacteria in milk samples from cows with
      clinical mastitis is central to proper treatment. In Denmark, time to bacterial
      diagnosis is typically 24 to 48 h when using traditional culturing methods. The
      PCR technique provides a faster and highly sensitive identification of bacterial
      pathogens, although shipment of samples to diagnostic laboratories delays
      treatment decisions. Due to the lack of fast on-site tests that can identify the
      causative pathogens, antibiotic treatments are often initiated before bacterial
      identification. The present study describes a flow cytometry-based method, which
      can detect and distinguish gram-negative and gram-positive bacteria in mastitis
      milk samples. The differentiation was based on bacterial fluorescence intensities
      upon labeling with biotin-conjugated wheat germ agglutinin and acridine orange.
      Initially 19 in-house bacterial cultures (4 gram-negative and 15 gram-positive
      strains) were analyzed, and biotin-conjugated wheat germ agglutinin and acridine
      orange florescence intensities were determined for gram-negative and gram
      positive bacteria, respectively. Fluorescence cut-off values were established
      based on receiver operating characteristic curves for the 19 bacterial cultures.
      The method was then tested on 53 selected mastitis cases obtained from the
      department biobank (milk samples from 6 gram-negative and 47 gram-positive
      mastitis cases). Gram-negative bacteria in milk samples were detected with a
      sensitivity of 1 and a specificity of 0.74, when classification was based on the
      previously established cut-off values. However, when receiver operating
      characteristic curves were constructed for the 53 mastitis cases, results
      indicate that a sensitivity and specificity of 1 could be reached if cut-off
      values were reduced. This flow cytometry-based technique could potentially
      provide dairy farmers and attending veterinarians with on-site information on
      bacterial gram-type and prevent ineffective antimicrobial treatment in mastitis
      cases caused by gram-negative bacteria.

PMID- 23141827
TI  - Peripartum infection with Streptococcus uberis but not coagulase-negative
      staphylococci reduced milk production in primiparous cows.
AB  - The effect of an intramammary infection (IMI) at calving on the milk yield of
      heifers during their first 200 d in milk (DIM) was estimated by comparing
      monozygotic twins, where one member had a naturally occurring IMI detected at the
      first milking after calving and the other twin did not. Data collected weekly
      over a full lactation for 29 twin pairs were used to estimate the effects of a
      peri-calving Streptococcus uberis IMI on milk yield and composition. Data for 19
      twin pairs were used to estimate the effects of pericalving coagulase-negative
      staphylococci (CNS) IMI. A heifer with a Strep. uberis IMI produced 200 kg (7%)
      less milk during the first 200 d of lactation compared with her uninfected twin,
      with significant differences evident throughout the 200-d period. Similar milk
      losses were recorded for heifers that developed CM or remained subclinical. An
      elevated milk SCC for infected heifers was only apparent for the first month (d 2
      30), although SCC tended to remain high during the second (d 31-60) and third (d
      61-90) months. Milk protein concentrations were greater in the Strep. uberis
      infected twin over the 200-d period, whereas fat and lactose concentrations
      showed little change. An IMI caused by Strep. uberis was associated with a lower
      milk yield, whereas an IMI by CNS was not, despite CNS-infected twins having a
      higher SCC than their uninfected twin for the first 30 d of lactation.

PMID- 23141828
TI  - Identification of lactoferrin peptides generated by digestion with human
      gastrointestinal enzymes.
AB  - Lactoferrin (LF) is a protein present in milk and other body fluids that plays
      important biological roles. As part of a diet, LF must survive gastrointestinal
      conditions or create bioactive fragments to exert its effects. The degradation of
      LF and formation of bioactive peptides is highly dependent on individual
      variation in intraluminal composition. The present study was designed to compare
      the degradation and peptide formation of bovine LF (bLF) following in vitro
      digestion under different simulated intraluminal conditions. Human
      gastrointestinal (GI) juices were used in a 2-step model digestion to mimic
      degradation in the stomach and duodenum. To account for variation in the
      buffering capacity of different lactoferrin-containing foods, gastric pH was
      adjusted either slowly or rapidly to 2.5 or 4.0. The results were compared with
      in vivo digestion of bLF performed in 2 volunteers. High concentration of GI
      juices and fast pH reduction to 2.5 resulted in complete degradation in the
      gastric step. More LF resisted gastric digestion when pH was slowly reduced to
      2.5 or 4.0. Several peptides were identified; however, few matched with
      previously reported peptides from studies using nonhuman enzymes. Surprisingly,
      no bovine lactoferricin, f(17-41), was identified during in vitro or in vivo
      digestion under the intraluminal conditions used. The diversity of enzymes in
      human GI juices seems to affect the hydrolysis of bLF, generating different
      peptide fragments compared with those obtained when using only one or a few
      proteases of animal origin. Multiple sequence analysis of the identified peptides
      indicated a motif consisting of proline and neighboring hydrophobic residues that
      could restrict proteolytic processing. Further structure analysis showed that
      almost all proteolytic cutting sites were located on the surface and mainly on
      the nonglycosylated half of lactoferrin. Digestion of bLF by human enzymes may
      generate different peptides from those found when lactoferrin is digested by
      nonhuman enzymes. The degradation of LF in the GI tract should be taken into
      consideration when health effects are proposed, because LF has now been approved
      by the European Food Safety Authority as a dietary supplement in food products.

PMID- 23141829
TI  - Characterization of the ability of coagulase-negative staphylococci isolated from
      the milk of Canadian farms to form biofilms.
AB  - Mastitis is the most common and detrimental infection of the mammary gland in
      dairy cows and has a major economic impact on the production of milk and dairy
      products. Bacterial mastitis is caused by several pathogens, and the most
      frequently isolated bacterial species are coagulase-negative staphylocci (CNS).
      Although CNS are considered minor mastitis pathogens, the importance of CNS has
      increased over the years. However, the mechanism and factors involved in CNS
      intramammary infection are poorly studied and defined. Biofilms have been
      proposed as an important component in the persistence of CNS intramammary
      infection. Biofilms are defined as a cluster of bacteria enclosed in a self
      produced matrix. The objectives of this study were to investigate the ability of
      CNS to form biofilms. A total of 255 mastitis-associated CNS isolates were
      investigated using a standard microtiter plate biofilm assay. The biofilms of
      some isolates were also observed by using confocal microscopy. The presence of
      biofilm-associated genes icaA, bap, aap, embP, fbe, and atlE was determined by
      PCR in the 255 isolates. The 5 dominant species assayed were Staphylococcus
      chromogenes (n=111), Staphylococcus simulans (n=53), Staphylococcus xylosus
      (n=25), Staphylococcus haemolyticus (n=15), and Staphylococcus epidermidis
      (n=13), and these represented 85% of the isolates. The data gathered were
      analyzed to identify significant links with the data deposited in the Canadian
      Bovine Mastitis Research Network database. Overall, Staph. xylosus is the species
      with the strongest ability to form biofilm, and Staph. epidermidis is the species
      with the lowest ability to form biofilm. Regardless of the species, the presence
      of icaA, bap, or the combination of multiple genes was associated with a greater
      ability to form biofilm. A strong relationship between the strength of a biofilm
      and days in milk was also noted, and CNS isolated later in the lactation cycle
      appeared to have a greater ability to form biofilm than those isolated earlier in
      the lactation cycle. In conclusion, Staph. xylosus is the species with the
      strongest biofilm formation ability. Furthermore, days in milk and gene
      combinations are predicted to be the variables with the strongest effect on
      biofilm formation by CNS.

PMID- 23141830
TI  - Short communication: Effect of heat stress during the dry period on gene
      expression in mammary tissue and peripheral blood mononuclear cells.
AB  - Heat stress (HT) during the dry period compromises mammary gland development,
      decreases future milk production, and impairs the immune status of dairy cows.
      Our objective was to evaluate the effect of cooling HT cows during the dry period
      on gene expression of the mammary gland and peripheral blood mononuclear cells
      (PBMC). Cows were dried off 46 d before their expected calving and assigned to 2
      treatments, HT or cooling (CL). Cows in the CL group were cooled with sprinklers
      and fans whereas HT cows were not. After parturition, all cows were housed in a
      freestall barn with cooling. The PBMC were isolated at dry-off and at -20, 2, and
      20 d relative to calving from a subset of cows (HT, n=9; CL, n=10), and mammary
      biopsies were taken at the same intervals (HT, n=7; CL, n=6) for RNA extraction.
      Gene expression was assessed using a custom multiplex gene expression assay based
      on traditional reverse transcription-PCR. Genes involved in prolactin (PRL)
      signaling [PRL receptor long form, PRL receptor short form, suppressor of
      cytokine signaling (SOCS)2, SOCS3, IGF2, IGF binding protein 5, and cyclin D1],
      fatty acid metabolism (acetyl-CoA carboxylase alpha (ACACA) and lipoprotein
      lipase (LPL)], and IGF1 were evaluated in mammary tissue, and genes related to
      fatty acid metabolism [ACACA, fatty acid synthase (FASN), and LPL], cytokine
      production [IL6, IL8, and tumor necrosis factor (TNF)], and IGF1 were evaluated
      in PBMC. No differences were observed in PRL signaling or fatty acid metabolism
      gene expression in the mammary gland. In PBMC, HT cows had greater mRNA
      expression of IGF1 and TNF during the transition period relative to CL and
      upregulated IL8 and downregulated FASN mRNA expression at 2 d relative to
      calving. We conclude that cooling HT cows during the dry period alters expression
      of genes involved in cytokine production and lipid metabolism in PBMC.

PMID- 23141831
TI  - Replacing alfalfa or red clover silage with birdsfoot trefoil silage in total
      mixed rations increases production of lactating dairy cows.
AB  - The objective of this study was to compare milk production and nutrient
      utilization in dairy cattle fed silage made from alfalfa (AL) or red clover (RC)
      versus birdsfoot trefoil (BFT) selected for low, normal, and high levels of
      condensed tannins. Condensed tannin contents of the 3 BFT silages were 8, 12, and
      16 g/kg of DM by butanol-HCl assay. Twenty-five multiparous Holstein cows (5
      fitted with ruminal cannulas) were blocked by days in milk and randomly assigned
      within blocks to incomplete 5*5 Latin squares. Diets contained [dry matter (DM)
      basis] about 60% AL, 50% RC, or 60% of 1 of the 3 BFT; the balance of dietary DM
      was largely from high-moisture corn plus supplemental crude protein from soybean
      meal. Diets were balanced to approximately 17% crude protein and fed for four 3
      wk periods; 2 wk were allowed for adaptation and production data were collected
      during the last week of each period. No differences existed in DM intake or milk
      composition due to silage source, except that milk protein content was lowest for
      RC. Yields of milk, energy-corrected milk, fat, protein, lactose, and solids-not
      fat were greater for the 3 BFT diets than for diets containing AL or RC. Feeding
      BFT with the highest condensed tannin content increased yield of milk, protein,
      and solids-not-fat compared with BFT containing the lowest amount of condensed
      tannin. Moreover, milk-N/N-intake was higher, and milk urea nitrogen
      concentration and urinary urea-N excretion were lower for diets with normal
      levels of BFT than for AL or RC diets. Feeding RC resulted in the highest
      apparent digestibility of DM, organic matter, neutral detergent fiber, acid
      detergent fiber, and hemicellulose and lowest ruminal concentrations of ammonia
      and free amino acids. Ruminal branched-chain volatile fatty acid levels were
      lowest for RC diets and diets with high levels of BFT and highest for the AL
      diet. Overall, diets containing BFT silage supported greater production than
      diets containing silage from AL or RC. The results indicated that feeding BFT or
      other legume silages containing condensed tannins can enhance performance and N
      utilization in lactating dairy cows.

PMID- 23141832
TI  - Localization of ghrelin and its receptor in the reproductive tract of Holstein
      heifers.
AB  - The aim of this experiment was to localize the mRNA and protein of ghrelin and
      its active receptor, growth hormone secretagogue 1A (GHS-R1A), within the
      reproductive tract of dairy cattle. Ghrelin is an orexigenic hormone that has
      been identified as a potent regulator of energy homeostasis. Recent evidence
      suggests that ghrelin may also serve as a metabolic signal to the reproductive
      tract. Ghrelin and GHS-R1A have been identified in the reproductive tract of
      several species, including humans, mice, and rats. However, ghrelin and GHS-R1A
      expression have not been described within bovine reproductive tissues. Therefore,
      the ampulla, isthmus, uterine body, corpus luteum, and follicles were harvested
      from 3 Holstein heifers (15.91+/-0.07 mo of age) immediately following
      exsanguination. Duodenum and hypothalamus were collected as positive controls for
      ghrelin and GHS-R1A, respectively. Tissues were fixed in 10% formalin and
      embedded in paraffin for microscopy. Additional samples were stored at -80
      degrees C for detection of mRNA. Ghrelin and GHS-R1A mRNA and protein were
      observed in all tissue types within the reproductive tract of dairy heifers;
      however, expression appeared to be cell specific. Furthermore, ghrelin protein
      appeared to be localized to the cytoplasm, whereas GHS-R1A protein was found on
      the plasma membrane. Within the reproductive tissues, ghrelin mRNA and protein
      were most abundantly expressed in the ampulla of the oviduct. Concentrations of
      GHS-R1A were lower than those of ghrelin but differed between tissues. This is
      one of the first studies to provide molecular evidence for the presence of
      ghrelin and GHS-R1A within the entire reproductive tract. However, implications
      for fertility remain to be determined.

PMID- 23141833
TI  - Milk fat depression induced by dietary marine algae in dairy ewes: persistency of
      milk fatty acid composition and animal performance responses.
AB  - Addition of marine algae (MA) to the diet of dairy ruminants has proven to be an
      effective strategy to enhance the milk content of some bioactive lipids, but it
      has also been associated with the syndrome of milk fat depression. Little is
      known, however, about the persistency of the response to dietary MA in sheep.
      Based on previous experiments with dairy ewes fed sunflower oil plus MA, it was
      hypothesized that the response might be mediated by time-dependent adaptations of
      the rumen microbiota, which could be evaluated indirectly through milk fatty acid
      (FA) profiles. Animal performance and milk FA composition in response to MA in
      the diet were studied using 36 Assaf ewes distributed in 6 lots and allocated to
      2 treatments (3 lots/treatment) consisting of a total mixed ration (40:60
      forage:concentrate ratio) supplemented with 25 g of sunflower oil (SO)/kg of dry
      matter plus 0 (SO; control diet) or 8 g of MA/kg of dry matter (SOMA diet). Milk
      production and composition, including FA profile, were analyzed on d 0, 6, 12,
      18, 24, 34, 44, and 54 of treatment. Diet supplementation with MA did not affect
      milk yield but did decrease milk fat content. Differences in the latter were
      detected from d 18 onward and reached -17% at the end of the experiment (i.e., on
      d 54). Compared with the control diet, the SOMA diet caused a reduction in milk
      18:0 and its desaturation product (cis-9 18:1) that lasted for the whole
      experimental period. This decrease, together with the progressive increase in
      some putative fat synthesis inhibitors, especially trans-10 18:1, was related to
      the persistency of milk fat depression in lactating ewes fed MA. Additionally,
      inclusion of MA in the diet enhanced the milk content of trans-11 18:1, cis
      9,trans-11 18:2, and C20-22 n-3 polyunsaturated FA, mainly 22:6 n-3. Overall, the
      persistency of the responses observed suggests that the ruminal microbiota did
      not adapt to the dietary supply of very long chain n-3 polyunsaturated fatty
      acids.

PMID- 23141834
TI  - Performance of dairy cows fed high levels of acetic acid or ethanol.
AB  - Ethanol and acetic acid are common end products from silages. The main objective
      of this study was to determine whether high concentrations of ethanol or acetic
      acid in total mixed ration would affect performance in dairy cows. Thirty mid
      lactation Holstein cows were grouped in 10 blocks and fed one of the following
      diets for 7 wk: (1) control (33% Bermuda hay + 67% concentrates), (2) ethanol
      [control diet + 5% ethanol, dry matter (DM) basis], or (3) acetic acid (control
      diet + 5% acetic acid, DM basis). Ethanol and acetic acid were diluted in water
      (1:2) and sprayed onto total mixed rations twice daily before feeding. An equal
      amount of water was mixed with the control ration. To adapt animals to these
      treatments, cows were fed only half of the treatment dose during the first week
      of study. Cows fed ethanol yielded more milk (37.9 kg/d) than those fed the
      control (35.8 kg/d) or acetic acid (35.3 kg/d) diets, mainly due to the higher DM
      intake (DMI; 23.7, 22.2, and 21.6 kg/d, respectively). The significant diet *
      week interaction for DMI, mainly during wk 2 and 3 (when acetic acid reached the
      full dose), was related to the decrease in DMI observed for the acetic acid
      treatment. There was a diet * week interaction in excretion of milk energy per
      DMI during wk 2 and 3, due to cows fed acetic acid sustained milk yield despite
      lower DMI. Energy efficiency was similar across diets. Blood metabolites
      (glucose, insulin, nonesterified fatty acids, ethanol, and gamma-glutamyl
      transferase activity) and sensory characteristics of milk were not affected by
      these treatments. Animal performance suggested similar energy value for the diet
      containing ethanol compared with other diets. Rumen conversion of ethanol to
      acetate and a concomitant increase in methane production might be a plausible
      explanation for the deviation of the predicted energy value based on the heat of
      combustion. Therefore, the loss of volatile compounds during the drying process
      in the laboratory should be considered when calculating energy content of
      fermented feedstuffs.

PMID- 23141835
TI  - The relationship between fertility and lactation characteristics in Holstein cows
      on United Kingdom commercial dairy farms.
AB  - Higher milk production is commonly associated with poorer fertility in dairy
      cows. This study used a biological model of lactation to define more closely
      which characteristics of lactation were linked to increased calving interval, an
      easily recorded measure of fertility in commercial dairy herds. Large data sets
      from a national milk recording scheme in the United Kingdom, collected over a 10
      yr period, were used to calculate the genetic and phenotypic correlations between
      calving interval and a range of lactation traits within the Holstein breed. A
      lactation curve was fitted to each lactation, and several characteristics of each
      lactation were calculated. These were used in a series of mixed-model bivariate
      analyses with calving interval to derive the genetic parameters. When heifer
      lactation curve trait data were used, the highest genetic correlations were found
      with peak yield, maximum secretion potential, and total lactation milk yield
      (0.59+/-0.06 to 0.63+/-0.05), reflecting the observed phenomenon of poorer
      fertility and higher milk production. Genetic correlations for calving interval
      were also calculated with the rate of increase in milk yield in early lactation
      (0.46+/-0.08), persistency (0.36+/-0.09), day of peak yield (0.20+/-0.02), and
      relative cell death rate (-0.12+/-0.09). The daily production of milk components
      was highly genetically correlated with calving interval, with values for fat,
      protein, lactose, and water being 0.73+/-0.15, 0.48+/-0.13, 0.57+/-0.13, and
      0.50+/-0.13. With these results and breeding values derived from these analyses,
      2 possible strategies were suggested for improving the relationship between milk
      yield and fertility in dairy cows. First, animals that break the correlations
      described above could be selected (e.g., bulls with high peak yield and low
      calving intervals). Second, animals with lower peak yields but better persistency
      could be selected to maintain total milk yield.

PMID- 23141836
TI  - Concentrations of nonesterified fatty acids and glucose in blood of
      periparturient dairy cows are indicative of pregnancy success at first
      insemination.
AB  - Greater blood concentrations of nonesterified fatty acids (NEFA) and lesser blood
      concentrations of glucose are indicative of the normal process of nutrient
      partitioning that occurs in early postpartum dairy cows. The objective was to
      determine the relationship between blood NEFA and glucose concentrations and
      subsequent conception at first insemination in postpartum dairy cows. Holstein
      (n=148) and Guernsey (n=8) dairy cows were blood sampled at approximately d 10,
      7, and 3 prepartum, on the day of calving and 3, 7, 14, and 21 d postpartum for
      measurement of NEFA and glucose concentrations. Serum and plasma were harvested
      and used for measurement of NEFA and glucose concentrations, respectively. Cows
      were given a presynchronization treatment (2 injections of PGF(2alpha) 14 d
      apart) with the second PGF(2alpha) injection occurring 14 d before the initiation
      of the timed AI (TAI) protocol. Blood for determination of progesterone
      concentrations was collected at each presynchronization injection and at the
      initiation of the TAI protocol that was used for first insemination (74+/-7 d
      postpartum). Cows were considered noncycling if serum progesterone concentrations
      at the 2 presynchronization PGF(2alpha) injections (d 37 and 51+/-7 postpartum)
      and at the initiation of the TAI protocol (d 65+/-7 postpartum) were <=1 ng/mL,
      and there was no indication of ovulation or presence of a corpus luteum by
      ultrasound examination at the initiation of the TAI protocol. Pregnancy was
      determined at 33 d and again at 61 d after first insemination by using
      ultrasound. Across all days, serum NEFA and plasma glucose concentrations were
      not different between cows that ovulated before the initiation of the TAI program
      (cycling) compared with those that did not ovulate (noncycling). Serum NEFA
      concentrations, however, were less and plasma glucose concentrations were greater
      during the early postpartum period for cows that subsequently became pregnant at
      first insemination compared with those that failed to become pregnant. Logistic
      regressions were used to predict the probability of pregnancy based on NEFA and
      glucose concentrations from individual days. The prediction with the greatest
      likelihood ratio was for d 3 postpartum NEFA and glucose concentrations.
      Nutritional status during the early postpartum period (within 1 wk after
      calving), as indicated by blood NEFA and glucose concentrations, may affect
      subsequent fertility by a mechanism that is independent from interval to first
      ovulation.

PMID- 23141837
TI  - The contribution of sublingual immunotherapy to the achievement of control in
      birch-related mild persistent asthma: a real-life randomised trial.
AB  - BACKGROUND: Asthma control represents the main goal of asthma management and
      different strategies aim to avoid the long term downsides of inhaled
      corticosteroids. We investigated in real-life conditions the contribution of
      sublingual immunotherapy in achieving the control of birch-related mild
      persistent asthma compared to two usual step-up therapeutic options. METHODS: A
      three-year open randomised study included 84 asthmatics, uncontrolled during the
      previous birch pollen season, despite a treatment with budesonide 400MUg/day.
      Patients randomly received budesonide 800MUg/day, budesonide 1600MUg/day,
      budesonide 400MUg/day plus montelukast 10MUg/day and budesonide 400MUg/day plus
      carbamylated allergoid of betulaceae pre-coseasonally. Asthma Control test,
      combined allergy symptoms and medications score, albuterol consumption, lung
      function, nasal eosinophils and nasal steroids usage were assessed as changes
      from the first to last pollen season. RESULT: Seventy-six patients concluded the
      study. All options, except budesonide 800MUg/day, produced an improvement of mean
      monthly Asthma Control test (p<0.05). Patients undergoing low-dose budesonide
      plus immunotherapy achieved, after three years, an appreciable control (ACT mean
      score 24). A significant improvement was seen in all groups for allergy symptoms
      plus medications and bronchial reactivity. Albuterol consumption and lung
      function improved in all but the first group. Only budesonide plus immunotherapy
      reduced nasal eosinophils and nasal steroids usage. Two mild self-resolving
      adverse events were reported. CONCLUSIONS: For patients with respiratory allergy
      due to birch pollen and mild persistent asthma, sublingual immunotherapy added to
      low-dose inhaled corticosteroids appears effective in maintaining long-term
      seasonal asthma control, representing a safe opportunity to reduce the cumulative
      amount of delivered corticosteroids.

PMID- 23141838
TI  - First annual register of allergenic pollen in Talca, Chile.
AB  - BACKGROUND: There are no data on atmospheric pollen in Talca. In the present
      work, our aim is to describe the amount of pollen grain in the atmosphere of the
      city of Talca likely to cause pollinosis of its inhabitants. METHODS: A
      volumetric Hirst sampler (Burkard seven-day recording device) was used to study
      pollen levels. It was placed in the centre of Talca from May 2007 to April 2008.
      RESULTS: The highest airborne presence of pollen, as measured in weekly averages,
      was Platanus acerifolia with a maximum weekly daily average of 203 grains/m3
      registered during September and October. The second highest was Acer
      pseudoplatanus with a maximum weekly daily average of 116 grains/m3. Populus spp.
      had a maximum weekly daily average 103 grains/m3. Olea europaea reached 19
      grains/m3 in November. Grasses presented high levels of pollen counts with a
      maximum weekly daily average of 27 grains/m3 from the end of August until the end
      of January. Pollens of Plantago spp. Rumex acetosella and Chenopodium spp. had a
      similar distribution and were present from October to April with maximum weekly
      daily average of 7 grains/m3, 7 grains/m3 and 3 grains/m3 respectively.
      Significant concentrations of Ambrosia artemisiifolia were detected from February
      until April. CONCLUSION: The population of Talca was exposed to high
      concentrations of allergenic pollen, such as P. acerifolia, A. pseudoplatanus,
      and grasses in the months of August through November. The detection of O.
      europaea and A. artemisiifolia is important as these are emergent pollens in the
      city of Talca. Aerobiological monitoring will provide the community with reliable
      information about the level of allergenic pollens, improving treatment and
      quality of life of patients with respiratory allergy.

PMID- 23141839
TI  - On the evolutionary conservation of protein dynamics: comment on "Comparing
      proteins by their internal dynamics: exploring structure-function relationships
      beyond static structural alignments" by Cristian Micheletti.

PMID- 23141840
TI  - Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) in biosolids from
      municipal wastewater treatment plants in China.
AB  - Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) along with methoxylated
      polybrominated diphenyl ethers (MeO-PBDEs) have been frequently identified as
      natural compounds in marine environment and also assumed as metabolites of PBDEs.
      In the present study, nine OH-PBDE, nine MeO-PBDE and 10 PBDE congeners were
      studied in the sewage sludge collected from 36 municipal wastewater treatment
      plants (WWTPs) in 27 cities of China. The results suggest that OH-PBDEs and PBDEs
      are ubiquitous in sewage sludge in China, however, methoxylated PBDEs were not
      detectable. Composition profiles of detected OH-PBDE congeners were different
      depending on the sampling location. SigmaOH-PBDEs in WWTPs sludge ranged from
      0.04 to 2.24 ng g(-1) dry weight (mean: 0.35 ng g(-1) dry weight). The total
      amount of the two most prominent congeners (6-OH-BDE-47+2'-OH-BDE-68) accounted
      for about 53.3-100% of the sum of all six identified congeners. A significant
      linear relationship was found between 6-OH-BDE-47 and 2'-OH-BDE-68. A distinct
      geographical distribution of SigmaOH-PBDEs was observed with greater
      concentrations of OH-PBDEs at coastal areas than inland regions in China.

PMID- 23141841
TI  - Effect of copper(II) on biodegradation of benzo[a]pyrene by Stenotrophomonas
      maltophilia.
AB  - Benzo[a]pyrene (BaP) biodegradation by Stenotrophomonas maltophilia was studied
      under the influence of co-existed Cu(II) ions. About 45% degradation was achieved
      within 3d when dealing with 1 mg L(-1) BaP under initial natural pH at 30 
      degrees C; degradation reached 48% in 2 d at 35  degrees C. Efficacy of BaP
      biodegradation reached the highest point at pH 4. In the presence of 10 mg L(-1)
      Cu(II) ions, the BaP removal ratio was 45% on 7th day, and maintained stable from
      7 to 14 d at 30  degrees C under natural pH. The favorable temperature and pH for
      BaP removal was 25  degrees C and 6.0 respectively, when Cu(II) ions coexisted in
      the solutions. Experiments on cometabolism indicated that S. maltophilia
      performed best when sucrose was used as an additional carbon source. GC-MS
      analysis revealed that the five rings of BaP opened, producing compounds with one
      or two rings which were more bioavailable.

PMID- 23141842
TI  - Influence of mature compost amendment on total and bioavailable polycyclic
      aromatic hydrocarbons in contaminated soils.
AB  - A laboratory microcosm study was carried out to assess the influence of compost
      amendment on the degradation and bioavailability of PAHs in contaminated soils.
      Three soils, contaminated with diesel, coal ash and coal tar, respectively, were
      amended with two composts made from contrasting feedstock (green waste and
      predominantly meat waste) at two different rates (250 and 750 t ha(-1)) and
      incubated for 8 months. During this period the treatments were sampled for PAH
      analysis after 0, 3, 6 and 8 months. Total and bioavailable fractions were
      obtained by sequential ultrasonic solvent extraction and hydroxypropyl-beta
      cyclodextrin extraction, respectively, and PAHs were identified and quantified by
      GC-MS. Bioavailability decrease due to sorption was only observed at the first 3
      months in the diesel spiked soil. After 8 months, compost addition resulted in
      over 90% loss of total PAHs irrespective of soil types. Desorption and
      degradation contributed to 30% and 70%, respectively, of the PAH loss in the
      spiked soil, while PAH loss in the other two soils resulted from 40% enhanced
      desorption and 60% enhanced degradation. Compost type and application rates had
      little influence on PAH bioavailability, but higher PAH removal was observed at
      higher initial concentration during the early stage of incubation. The
      bioavailable fraction of PAH was inversely correlated to the number of benzene
      rings and the octanol-water partition coefficient. Further degradation was not
      likely after 8-month although over 30% of the residual PAHs were bioavailable,
      which highlighted the application of bioavailability concept during remediation
      activities.

PMID- 23141843
TI  - Electron transfer sensitized photodechlorination of surfactant solubilized PCB
      138.
AB  - Sensitized photodechlorination of polychlorinated biphenyl, PCB 138, in three
      different surfactant solutions was studied. The sensitizer of choice was leuco
      methylene blue, which was produced in situ from methylene blue using either
      triethylamine or sodium borohydride. Three types of surfactants, anionic (SDS),
      neutral (TWEEN 80), and cationic (CTAB) at different concentrations were
      investigated. The neutral and cationic surfactants were found to be more
      effective than anionic. In each case the surfactant concentration was found to
      play a significant role in the rate of dechlorination. For different sensitized
      systems (triethylamine or sodium borohydride), a different product distribution
      and a different pathway of dechlorination was observed.

PMID- 23141844
TI  - PCDD/Fs and PCBs in ambient air in a highly industrialized city in northern
      Italy.
AB  - Ambient air samples were collected in five locations around a polychlorobiphenyl
      (PCB) production plant in a highly industrialized city in the north of Italy, for
      the analysis of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated
      dibenzofurans (PCDFs) and PCBs. PCDD/F atmospheric concentrations were lower than
      those generally detected in urban areas, while PCB concentrations were higher
      than in urban and industrialized areas in other countries, especially in the
      locations closest to the plant. To identify source emissions responsible for air
      pollution we used principal component analysis (PCA) to compare the "fingerprint"
      of the air in Brescia with some source-related experimental and published data.
      This analysis showed that the PCDD/F fingerprints were more similar to steel
      plant emission data, while none of the PCB air patterns were comparable to
      emission profiles, indicating that different sources are responsible for the
      concentration of these two pollutants. The highest PCB concentrations detected in
      the areas closest to the chemical plant are indicative of its impact on the
      surrounding environment.

PMID- 23141845
TI  - Real-world economic burden of venous thromboembolism and antithrombotic
      prophylaxis in medical inpatients.
AB  - INTRODUCTION: Venous thromboembolism (VTE) is a significant cause of morbidity
      and mortality in medical patients, and the economic burden of this disease is
      plausibly relevant as well. However, few data from real-world observations are
      available on this topic. Aim of our study was to assess the costs of VTE
      management and antithrombotic prophylaxis in patients hospitalized in Internal
      Medicine (IM) departments. MATERIALS AND METHODS: The in-hospital paths of 160
      patients with VTE (VTE group) and 160 patients receiving prophylaxis and without
      VTE (NO-VTE group) were retrospectively evaluated within 26IM units in Italy. The
      economic analysis was undertaken by applying a process analysis, the initial
      phase of the more comprehensive Activity Based Costing technique. Accordingly to
      this approach, only information closely linked to VTE or its prevention was
      registered. RESULTS: The total median costs for VTE management were around four
      times higher than those for prophylaxis (? 1,348.68 vs ? 373.03). Human resources
      were the most important cost-driver (55.5% and 65.7% in the VTE and NO-VTE
      groups), followed by instrumental (24.6% in VTE and 15.5% in NO-VTE) and
      haematologic tests (12.6% in VTE patients and 13.3% in controls). In the NO-VTE
      group the direct costs for prophylaxis accounted for 4.5% of total. CONCLUSIONS:
      The real-world data of this study confirm the economic burden of in-hospital
      treatment of VTE, and the relatively low costs of thromboprophylaxis. A greater
      adherence to evidence-based protocols for VTE prevention could probably reduce
      the current financial burden of VTE on healthcare systems.

PMID- 23141846
TI  - Association between variation in ADAMTS13 and aneurysmal subarachnoid hemorrhage.

PMID- 23141847
TI  - Gender differences of bleeding and stroke risk in very old atrial fibrillation
      patients on VKA treatment: results of the EPICA study on the behalf of FCSA
      (Italian Federation of Anticoagulation Clinics).
AB  - INTRODUCTION: The prevalence of AF is higher in men and increases with age.
      However, the number of elderly women is higher than that of elderly men, and AF
      should be considered to affect men and women equally. Little information exists
      on elderly AF patients, and in particular, whether stroke and bleeding risk
      differs between elderly women and elderly men remains unknown. METHODS: We have
      performed the EPICA Study, a large, multicentre observational study including
      4093 elderly patients who started VKA treatment after the age of 80years. In this
      study, we will focus our analysis on 3015 AF patients followed for 7620 patient
      years (pt-yrs) to evaluate if bleeding and stroke risks were different between
      genders. RESULTS: During follow-up, we recorded 112 ischemic cerebral events
      (rate 1.5 *100pt-years) with no difference between genders. History of previous
      stroke/TIA, hypertension and artery vascular disease are independently associated
      with stroke/TIA during treatment. We recorded 132 major bleeds (rate 1.7 *100pt
      years); males showed a higher risk of bleeding (OR 1.5), even if not
      statistically significant. At multivariate analysis, history of major bleeds,
      history of falls and active cancer are risk factors independently associated to
      bleeding. CONCLUSION: Elderly patients with AF do not show clear gender related
      differences in the risk of major adverse events. However, elderly males showed a
      higher rate of bleeding complications, and females showed a slightly higher rate
      of stroke, thus suggesting the possibility of a higher net clinical benefit of
      anticoagulant treatment in females.

PMID- 23141848
TI  - Compound heterozygous mutations (p.Leu13Pro and p.Tyr294*) associated with factor
      VII deficiency cause impaired secretion through ineffective translocation and
      extensive intracellular degradation of factor VII.
AB  - INTRODUCTION: Congenital coagulation factor VII (FVII) deficiency is a rare
      coagulation disease. We investigated the molecular mechanisms of this FVII
      deficiency in a patient with compound heterozygous mutations. METHODS: A 22-year
      old Japanese female was diagnosed with asymptomatic FVII deficiency. The FVII
      activity and antigen were greatly reduced (activity, 13.0%; antigen, 10.8%). We
      analyzed the F7 gene of this patient and characterized mutant FVII proteins using
      in vitro expression studies. RESULTS: Sequence analysis revealed that the patient
      was compound heterozygous with a point mutation (p.Leu13Pro) in the central
      hydrophobic core of the signal peptides and a novel non-sense mutation
      (p.Tyr294*) in the catalytic domain. Expression studies revealed that mutant FVII
      with p.Leu13Pro (FVII13P) showed less accumulation in the cells (17.5%) and less
      secretion into the medium (64.8%) than wild type showed. Truncated FVII resulting
      from p.Tyr294* (FVII294X) was also decreased in the cells (32.0%), but was not
      secreted into the medium. Pulse-chase experiments revealed that both mutants were
      extensively degraded intracellularly compared to wild type. The majority of
      FVII13P cannot translocate into endoplasmic reticulum (ER). However, a small
      amount of FVII13P was processed normally with post-translational modifications
      and was secreted into the medium. The fact that FVII294X was observed only in ER
      suggests that it is retained in ER. Proteasome apparently plays a central role in
      these degradations. CONCLUSIONS: These findings demonstrate that both mutant
      FVIIs impaired secretion through ineffective translocation to and retention in ER
      with extensive intracellular degradation, resulting in an insufficient phenotype.

PMID- 23141849
TI  - Three-month mortality rate and clinical predictors in patients with venous
      thromboembolism and cancer. Findings from the RIETE registry.
AB  - Patients with venous thromboembolism (VTE), and particularly those with cancer,
      are at increased risk of recurrences, major bleeding, and short- / medium-term
      mortality. Data from 35,539 patients (6,075 of these with cancer), presenting
      with symptomatic VTE in the previous three months and enrolled in the worldwide
      RIETE registry, were evaluated to assess overall and pulmonary embolism (PE)
      related mortality, and their potential predictors, with particular focus on
      patients with cancer. Overall 3-month mortality in the total RIETE population was
      7.9%, and death was considered PE-related in 1.4%. Significantly more patients
      died among those with cancer (26.4%, vs 4.1% in no-cancer group, p<0.001). In
      3.0% of cancer patients death was considered PE-related, compared to 1.0% in no
      cancer group (p<0.001). Cancer was the strongest independent risk factor for both
      all-cause and PE-related mortality, and in the subgroup of cancer patients those
      with advanced disease, reduced mobility, chronic pulmonary disease, and those
      experiencing PE (vs isolated deep vein thrombosis) were at increased risk of PE
      related death. According to the findings of our very large, real-world registry,
      in the three months following an acute episode VTE remains a substantial cause of
      mortality. Cancer patients are at particular high risk of VTE-related death.
      Clinical factors predicting a fatal PE identified in this study (cancer,
      immobility, comorbidities, increasing age, PE at presentation), could be
      considered for risk stratification scheme for secondary prophylaxis in daily
      practice.

PMID- 23141850
TI  - Cellular imitations.
AB  - Synthetic biologists typically construct new pathways within existing cells.
      While useful, this approach in many ways ignores the undefined but necessary
      components of life. A growing number of laboratories have begun to try to remove
      some of the mysteries of cellular life by building life-like systems from non
      living component parts. Some of these attempts rely on purely chemical and
      physical forces alone without the aid of biological molecules, while others try
      to build artificial cells from the parts of life, such as nucleic acids,
      proteins, and lipids. Both bottom-up strategies suffer from the complication of
      trying to build something that remains undefined. The result has been the
      development of research programs that try to build systems that mimic in some way
      recognized living systems. Since it is difficult to quantify the mimicry of life,
      success often times is evaluated with a degree of subjectivity. Herein we
      highlight recent advances in mimicking the organization and behavior of cellular
      life from the bottom-up.

PMID- 23141851
TI  - Psychoendocrine and psychoneuroimmunological mechanisms in the comorbidity of
      atopic eczema and attention deficit/hyperactivity disorder.
AB  - Epidemiological data indicate that atopic eczema (AE) in infancy significantly
      increases the risk for attention deficit/hyperactivity disorder (ADHD) in later
      life. The underlying pathophysiological mechanisms of this comorbidity are
      unknown. We propose that the release of inflammatory cytokines caused by the
      allergic inflammation and/or elevated levels of psychological stress as a result
      of the chronic disease interfere with the maturation of prefrontal cortex regions
      and neurotransmitter systems involved ADHD pathology. Alternatively, increased
      stress levels in ADHD patients may trigger AE via neuroimmunological mechanisms.
      In a third model, AE and ADHD may be viewed as two separate disorders with one or
      more shared risk factors (e.g., genetics, prenatal stress) that increase the
      susceptibility for both disorders leading to the co-occurrence of AE and ADHD.
      Future investigation of these three models may lead to a better understanding of
      the mechanisms underlying the observed comorbidity between AE and ADHD and
      further, to targeted interdisciplinary primary prevention and treatment
      strategies.

PMID- 23141852
TI  - HFSA and AAHFN joint position statement: advocating for a full scope of nursing
      practice and leadership in heart failure.

PMID- 23141853
TI  - Heart failure in post-MI patients with persistent IRA occlusion: prevalence, risk
      factors, and the long-term effect of PCI in the Occluded Artery Trial (OAT).
AB  - BACKGROUND: The incidence and predictors of heart failure (HF) after myocardial
      infarction (MI) with modern post-MI treatment have not been well characterized.
      METHODS AND RESULTS: A total of 2,201 stable patients with persistent infarct
      related artery occlusion >24 hours after MI with left ventricular ejection
      fraction <50% and/or proximal coronary artery occlusion were randomized to
      percutaneous intervention plus optimal medical therapy (PCI) or optimal medical
      therapy (MED) alone. Centrally adjudicated HF hospitalizations for New York Heart
      Association (NYHA) III/IV HF and mortality were determined in patients with and
      without baseline HF, defined as a history of HF, Killip Class >I at index MI,
      rales, S3 gallop, NYHA II at randomization, or NYHA >I before index MI. Long-term
      follow-up data were used to determine 7-year life-table estimated event rates and
      hazard ratios. There were 150 adjudicated HF hospitalizations during a mean
      follow-up of 6 years with no difference between the randomized groups (7.4% PCI
      vs. 7.5% MED, P = .97). Adjudicated HF hospitalization was associated with
      subsequent death (44.0% vs. 13.1%, HR 3.31, 99% CI 2.21-4.92, P < .001). Baseline
      HF (present in 32% of patients) increased the risk of adjudicated HF
      hospitalization (13.6% vs. 4.7%, HR 3.43, 99% CI 2.23-5.26, P < .001) and death
      (24.7% vs. 10.8%, HR 2.31, 99% CI 1.71-3.10, P < .001). CONCLUSIONS: In the
      overall Occluded Artery Trial (OAT) population, adjudicated HF hospitalizations
      occurred in 7.5% of subjects and were associated with increased risk of
      subsequent death. Baseline or prior HF was common in the OAT population and was
      associated with increased risk of hospitalization and death.

PMID- 23141854
TI  - Minor myocardial damage is a prevalent condition in patients with acute heart
      failure syndromes and preserved systolic function with long-term prognostic
      implications: a report from the CIAST-HF (Collaborative Italo-Argentinean Study
      on cardiac Troponin T in Heart Failure) study.
AB  - BACKGROUND: Half of patients with acute heart failure syndromes (AHFS) have
      preserved left ventricular ejection fraction (PLVEF). In this setting, the role
      of minor myocardial damage (MMD), as identified by cardiac troponin T (cTnT),
      remains to be established. AIM: To evaluate the prevalence and long-term
      prognostic significance of cTnT elevations in patients with AHFS and PLVEF.
      PATIENTS AND METHODS: This retrospective, multicenter, collaborative study
      included 500 patients hospitalized for AHFS with PLVEF (ejection fraction >=40%)
      between October 2000 and December 2006. Blood samples were collected within 12
      hours after admission and were assayed for cTnT. MMD was defined as a cTnT value
      of >=0.020 ng/mL. RESULTS: Mean age was 73 +/- 12 years, 47% were female, 38% had
      an ischemic etiology, and New York Heart Association (NYHA) class was 2.2 +/-
      0.7. Mean cTnT value was 0.149 +/- 0.484 ng/mL, and cTnT was directly correlated
      with serum creatinine (Spearman's Rho = 0.35, P < .001) and NYHA class (0.25, P <
      .001). MMD was diagnosed in 220 patients (44%). Patients with MMD showed lower
      left ventricular ejection fraction (P < .05), higher serum creatinine (P < .001),
      higher prevalence of ischemic etiology and diabetes mellitus, a worse NYHA class
      (P < .001), and higher natriuretic peptide levels (P < .001) as compared with
      patients without MMD. At 6-month follow-up, overall event-free survival was 55%
      and 75% in patients with and without MMD (P < .001), respectively. On
      multivariate Cox regression analysis, only NYHA class (HR = 1.50; P = .002) and
      MMD (HR = 1.81; P = .001) were identified as predictors of events. CONCLUSIONS:
      Increased cTnT levels were detected in approximately 50% of patients with AHFS
      with preserved systolic function, and were found to correlate with clinical
      measures of disease severity. The presence of MMD was associated with a worse
      long-term outcome, lending support to cTnT-based risk stratification in the
      setting of AHFS.

PMID- 23141855
TI  - Age-related maximum heart rate among ischemic and nonischemic heart failure
      patients receiving beta-blockade therapy.
AB  - BACKGROUND: Equations to predict maximum heart rate (HR(max)) in heart failure
      (HF) patients receiving beta-adrenergic blocking (BB) agents do not consider the
      cause of HF. We determined equations to predict HR(max) in patients with ischemic
      and nonischemic HF receiving BB therapy. METHODS AND RESULTS: Using treadmill
      cardiopulmonary exercise testing, we studied HF patients receiving BB therapy
      being considered for transplantation from 1999 to 2010. Exclusions were pacemaker
      and/or implantable defibrillator, left ventricle ejection fraction (LVEF) >50%,
      peak respiratory exchange ratio (RER) <1.00, and Chagas disease. We used linear
      regression equations to predict HR(max) based on age in ischemic and nonischemic
      patients. We analyzed 278 patients, aged 47 +/- 10 years, with ischemic (n = 75)
      and nonischemic (n = 203) HF. LVEF was 30.8 +/- 9.4% and 28.6 +/- 8.2% (P = .04),
      peak VO(2) 16.9 +/- 4.7 and 16.9 +/- 5.2 mL kg(-1) min(-1) (P = NS), and the
      HR(max) 130.8 +/- 23.3 and 125.3 +/- 25.3 beats/min (P = .051) in ischemic and
      nonischemic patients, respectively. We devised the equation HR(max) = 168 - 0.76
      * age (R(2) = 0.095; P = .007) for ischemic HF patients, but there was no
      significant relationship between age and HR(max) in nonischemic HF patients (R(2)
      = 0.006; P = NS). CONCLUSIONS: Our study suggests that equations to estimate
      HR(max) should consider the cause of HF.

PMID- 23141856
TI  - Obesity and the response to intensified diuretic treatment in decompensated heart
      failure: a DOSE trial substudy.
AB  - BACKGROUND: Obesity could attenuate diuretic effectiveness in treatment of acute
      decompensated heart failure (HF). METHODS AND RESULTS: The DOSE trial randomized
      308 subjects with acute HF to low- versus high-intensification intravenous
      diuretic therapy. We tested for statistical interactions between obesity and
      dosing strategy across clinical end points. After 72 hours of treatment, obese
      subjects (body mass index >30 kg/m(2); n = 173) had greater volume loss than
      nonobese subjects (n = 119) but similar improvements in dyspnea and freedom from
      congestion. Both groups had greater fluid loss with high-intensification
      treatment. Obese subjects had a higher incidence of worsening renal function
      (WRF) at 72 hours with low-intensification treatment, compared with nonobese
      subjects. In contrast, nonobese and obese subjects had similar incidence of WRF
      with high-intensification treatment. There were no differences between obese and
      nonobese subjects in time to discharge and 60-day freedom from death, emergency
      department visit, or rehospitalization. CONCLUSIONS: The incidence of WRF was
      greater in obese than in nonobese subjects with low-intensification treatment.
      However, the frequency of WRF was equivalent in obese and nonobese subjects with
      high-intensification treatment. Additional studies are needed to assess whether
      obese patients with acute HF benefit from an initial high-intensification
      treatment strategy.

PMID- 23141857
TI  - Comorbidity significantly affects clinical outcome after cardiac
      resynchronization therapy regardless of ventricular remodeling.
AB  - BACKGROUND: The influence of comorbid conditions on ventricular remodeling,
      functional status, and clinical outcome after cardiac resynchronization therapy
      (CRT) is insufficiently elucidated. METHODS AND RESULTS: The influence of
      different comorbid conditions on left ventricular remodeling, improvement in New
      York Heart Association (NYHA) functional class, hospitalizations for heart
      failure, and all-cause mortality after CRT implantation was analyzed in 172
      consecutive patients (mean age 71 +/- 9 y), implanted from October 2008 to April
      2011 in a single tertiary care hospital. During mean follow-up of 18 +/- 9
      months, 21 patients died and 57 were admitted for heart failure. Left ventricular
      remodeling and improvement in NYHA functional class were independent from
      comorbidity burden. However, diabetes mellitus (hazard ratio [HR] 3.45, 95%
      confidence interval [CI] 1.24-9.65) and chronic kidney disease (HR 3.11, 95% CI
      1.10-8.81) were predictors of all-cause mortality, and the presence of chronic
      obstructive pulmonary disease (HR 1.89, 95% CI 1.02-3.53) was independently
      associated with heart failure admissions. Importantly, those 3 comorbid
      conditions had an additive negative impact on survival and heart failure
      admissions, even in patients with reverse left ventricular remodeling.
      CONCLUSIONS: Reverse ventricular remodeling and improvement in functional status
      after CRT implantation are independent from comorbidity burden. However, comorbid
      conditions remain important predictors of all-cause mortality and heart failure
      admissions.

PMID- 23141858
TI  - Heart failure and skilled nursing facilities: review of the literature.
AB  - BACKGROUND: Almost one-fourth of older adults hospitalized with heart failure
      (HF) are discharged to skilled nursing facilities (SNFs). The purpose of this
      review was to evaluate knowledge about HF patients discharged to SNFs to provide
      a foundation for future studies. METHODS AND RESULTS: A search was conducted of
      Medline, CINAHL, PubMed, and Google Scholar. Key words were heart failure,
      congestive heart failure, skilled care, skilled nursing care, skilled nursing
      facilities, nursing home, postacute care, postacute services, and subacute care.
      Publications (n = 37) were reviewed and categorized into case studies,
      editorials, clinical care, evaluation projects, and data-based publications. Of
      29 data-based publications, 6 were focused on factors associated with hospital
      readmission from postacute settings, 3 on trends in hospitalizations, 12 on
      hospital discharge to postacute services, 5 on rehabilitation services in
      postacute settings, 1 on cost, and 2 on interventions. Patients discharged to
      SNFs were at high risk for mortality and multiple hospitalizations. No HF
      specific care or guidelines were found at SNFs. Only 1 study evaluated quality of
      life at SNFs. CONCLUSIONS: Prospective studies are needed to evaluate the
      clinical condition of HF patients discharged to SNFs and the interventions they
      receive.

PMID- 23141859
TI  - A global transcriptome analysis of a dog model of congestive heart failure with
      the human genome as a reference.
AB  - BACKGROUND: The global molecular changes in cardiac tissue during congestive
      heart failure (CHF) have not been fully examined. Transcriptome analysis with the
      use of next-generation sequencers is a useful tool for elucidating the
      pathogenesis of CHF. Although there are some advantages in a dog CHF model,
      transcriptome analyses in dogs are limited by the relative lack of genomic
      information. METHODS AND RESULTS: The transcriptome analysis of hearts from dogs
      with CHF was conducted with the use of a genome analyzer and the Casava software.
      The mRNA sequence reads showed alignments with ~800 of 1,019 genes from the dog
      reference database. On the other hand, the reads aligned with ~15,000 of the
      21,407 genes in the hg19 human reference database. The correlation of expressed
      genes was extremely high (r = 0.93; P < .0001) between the dog and human
      databases. A pathway analysis using the hg19 reference revealed increased
      expression of p53 pathway-related (P < 10(-10)) and inflammatory interleukin
      related (P < 10(-10)) genes in the CHF model. CONCLUSIONS: The use of the human
      genome as a reference in global transcriptome analyses of dogs is a useful
      approach for investigating diseases such as CHF. Such an approach would also be
      useful for analyzing disease models in other experimental animals.

PMID- 23141860
TI  - Cardiac VEGF-B expression decreases along with cardiac allograft unload.

PMID- 23141861
TI  - Daytime PaO2 in OSAS, COPD and the combination of the two (overlap syndrome).
AB  - BACKGROUND: OSAS and COPD are often associated with day-time hypoxemia. Overlap
      Syndrome (OS), the association between both diseases, increases the risk of day
      time hypoxemia. The aim of this study was to investigate the mechanisms which
      could justify the low oxygen level and the effect of CPAP. METHODS: We performed
      a retrospective analysis in all patients referred to our institutes for suspected
      OSAS and who also underwent spirometry and blood gas analysis during our
      evaluation. Thus, 720 patients were selected. According to pulmonary function
      test parameters they were divided into 3 groups: OSAS (N = 466,65%); OS (N =
      168,23%) and COPD (N = 86,12%). In order to evaluate the differences between the
      three groups, ANOVA analyses were carried out, whereas a multivariate analysis
      was performed in order to evaluate which factors determine the diurnal PaO(2). In
      90 patients we also have the data on blood gas analysis after one year of CPAP
      treatment, so we evaluate the PaO(2) improvement in accordance with compliance to
      treatment in these patient subgroups. RESULTS: The OS group showed a lower level
      of daytime PaO(2) compared with OSAS patients and T90 was higher in OS compared
      with OSAS. A multivariate analysis showed that in the OS diurnal PaO(2)
      correlated with age (beta = -0.20) and moreover with FEV(1) (beta = 0.31) and T90
      (beta = 0.37), while in the OSAS a correlation was found with FEV(1) (beta = 
      0.11) and mostly with BMI (beta = 0.25), age and T90. In all patients with good
      compliance to CPAP day-time PaO(2) improved. CONCLUSIONS: Our data suggest that
      day-time hypoxemia in OSA patients is largely determined by the increase of body
      weight and severity of nocturnal hypoxia. However, CPAP therapy has been shown to
      improve daytime PaO(2) values both in OSAS and in OS.

PMID- 23141862
TI  - Total knee arthroplasty with fully porous-coated stems for the treatment of large
      bone defects.
AB  - Between February1999 and April 2006, 25 patients (28 knees) underwent a TKA by a
      single surgeon. At an average final follow-up of 7+/-2years (range, 3-10years),
      34 (100%) of 34 fully porous stems had achieved bone ingrowth. However, one case
      (3%) had a component loosening due to the de-bonding of sheets of beads from the
      stem. The remaining cases remained well fixed. Three well-fixed stems in 2
      patients failed from deep infection. There was one reoperation required for a
      femoral periprosthetic fracture. Our 10-year experience shows that fully porous
      coated stems reliably achieve durable fixation in complex primary and revision
      TKA allowing the surgeon to bypass large bone defects and gain fixation in
      diaphyseal bone.

PMID- 23141863
TI  - Adverse tissue reactions in modular exchangeable neck implants: a report of two
      cases.
AB  - Dual-modular femoral stems with exchangeable necks theoretically allow
      optimization of hip joint biomechanics via selective restoration of femoral
      anteversion, offset, and limb length. A potential disadvantage is the possible
      generation of metal ions and debris by fretting and crevice corrosion at the
      additional stem-neck interface. We present 2 cases of early-onset adverse
      inflammatory tissue reactions as a result of accelerated corrosion at the stem
      neck interface of a dual-modular implant, requiring subsequent revision of well
      fixed components.

PMID- 23141864
TI  - Higher body mass index leads to longer operative time in total knee arthroplasty.
AB  - Obesity has been shown to be a risk factor for degenerative knee arthritis and
      its incidence is increasing in epidemic proportions. Obesity has also been shown
      to be a risk factor for surgical complications associated with total knee
      replacement (TKR) surgery. There have been no prior investigations examining the
      relationship between body mass index (BMI) and surgical time during TKR. Two
      hundred and seventy three patients were evaluated and stratified by BMI. There
      was a direct linear relationship between BMI and operative time. In addition, the
      higher the BMI group, the younger the age at surgery, and obese class III
      patients experienced a higher rate of early post-operative complication.
      Therefore, patients should be counseled that obesity prior to TKR surgery might
      lead to a longer operative time and any sequelae associated with further exposure
      of the operative wound, especially with regard to higher rates of prosthetic
      joint infection (PJI).

PMID- 23141865
TI  - Validation of a short food frequency questionnaire to evaluate nutritional
      lifestyles in hypercholesterolemic patients.
AB  - OBJECTIVES: The purpose of our study was to develop and validate a short food
      frequency questionnaire which could assess the nutritional lifestyles of
      hypercholesterolemic patients consulting in daily practice. MATERIAL AND METHODS:
      The questionnaire explores 11 nutrient categories. Hundred and thirty-one
      patients were recruited for the construct validity and 58 patients for the
      external validity in La Pitie Hospital, Paris. The reference method used was the
      diet history. To measure the internal consistency and to test the sensibility to
      change on a large scale, the questionnaire was used in an observational study
      conducted in Spain in 1048 moderate hypercholesterolemic patients. Psychometric
      analyses included construct validity, internal consistency, test-retest
      reliability, external validity and sensibility to change. RESULTS: Validation of
      the questionnaire indicated a good internal consistency (Cronbach Coefficient
      Alpha at 0.69) and test-retest reliability (intraclass correlation
      coefficient=0.89). The correlation between the scores of the FFQ and those of the
      diet history was significant with a Pearson correlation coefficient at 0.3
      (P=0.029). The comparison between the ranking of the patients showed an agreement
      of 72% with a kappa of 0.48 [0.10; 0.69]. The sensibility to change was good with
      a score evolution improving one and four months after nutrition advices: 28.2% of
      patients ranked in group 1 at inclusion versus 61.3% (P<0.0001) at one month and
      75.2% (P<0.0001) at four months. CONCLUSION: In conclusion, we developed and
      validated a food questionnaire for hypercholesterolemic patients, which can be
      used as a therapeutic education tool in daily practice or in clinical research.

PMID- 23141866
TI  - GFR estimation using standardized cystatin C in kidney transplant recipients.
AB  - BACKGROUND: The utility of serum cystatin C (SCysC) as a filtration marker in
      kidney transplantation is uncertain. We took advantage of the recent validation
      of a reference calibrator for SCysC and of newly developed CKD-EPI (Chronic
      Kidney Disease Epidemiology Collaboration) equations (2012) expressed for use
      with standardized SCysC level to reassess the performance of SCysC as a
      filtration marker in kidney transplant recipients. STUDY DESIGN: Study of
      diagnostic test accuracy. SETTING & PARTICIPANTS: 670 kidney transplant
      recipients from 3 centers undergoing glomerular filtration rate (GFR)
      measurements from December 2006 to November 2012. INDEX TEST: Estimated GFR
      (eGFR) using the 2012 SCysC-based and serum creatinine (SCr)/SCysC-based CKD-EPI
      equations (eGFR(cys) and eGFR(cr-cys), respectively) and the 2009 SCr-based CKD
      EPI equation (eGFR(cr)), with SCysC and SCr measured at a single laboratory
      between April 2011 and June 2011. REFERENCE TEST: Measured GFR (mGFR) using
      urinary clearance of inulin. RESULTS: Bias (the difference between mGFR and eGFR)
      was significantly smaller for eGFR(cys) and eGFR(cr-cys) versus eGFR(cr) (-2.82
      and -0.54 vs +4.4 mL/min/1.73 m(2), respectively; P < 0.001). Precision (standard
      deviation of the mean bias) also was better for eGFR(cys) and eGFR(cr-cys) versus
      eGFR(cr) (12 and 11 vs 13 mL/min/1.73 m(2) [P < 0.001 for both comparisons]).
      Accuracy (percentage of GFR estimates within 30% of mGFR) was greater for
      eGFR(cys) and eGFR(cr-cys) versus eGFR(cr) (81% and 86% vs 75%, respectively [P =
      0.004 and P < 0.001]). Net reclassification index with respect to mGFR of 30
      mL/min/1.73 m(2) for eGFR(cr-cys) and eGFR(cys) versus eGFR(cr) was 18.8% [95%
      CI, 8.6%-28.9%] and 22.5% [95% CI, 10.2%-34.9%]. LIMITATIONS: Patients were
      exclusively of European descent; association with transplant outcome was not
      evaluated. CONCLUSIONS: Our data validate the use of both the newly developed
      SCysC-based and SCr/SCysC-based CKD-EPI equations (2012) in kidney transplant
      recipients. Both equations perform better than the SCr-based CKD-EPI equation
      (2009).

PMID- 23141867
TI  - Melodic pitch expectation interacts with neural responses to syntactic but not
      semantic violations.
AB  - Current behavioural and electrophysiological evidence suggests that music and
      language syntactic processing depends on at least partly shared neural resources.
      Existing studies using a simultaneous presentation paradigm are limited to the
      effects of violations of harmonic structure in Western tonal music on processing
      of single syntactic or semantic violations. Because melody is a universal
      property of music as it is emphasized also by non-western musical traditions, it
      is fundamental to investigate interactions between melodic expectation and
      language processing. The present study investigates the effect of melodically
      unexpected notes on neural responses elicited by linguistic violations. Sentences
      with or without a violation in the last word were presented on screen
      simultaneously with melodies whose last note had a high- or low-probability, as
      estimated by a computational model of melodic expectation. Violations in language
      could be syntactic, semantic or combined. The electroencephalogram (EEG) was
      recorded while participants occasionally responded to language stimuli.
      Confirming previous studies, low-probability notes elicited an enhanced N1
      compared to high-probability notes. Further, syntactic violations elicited a left
      anterior negativity (LAN) and P600 component, and semantic violations elicited an
      N400. Combined violations elicited components which resembled neural responses to
      both syntactic and semantic incongruities. The LAN amplitude was decreased when
      language syntactic violations were presented simultaneously with low-probability
      notes compared to when they were presented with high-probability notes. The N400
      was not influenced by the note-probability. These findings show support for the
      neural interaction between language and music processing, including novel
      evidence for melodic processing which can be incorporated in a computational
      framework of melodic expectation. 

PMID- 23141868
TI  - Natural resource manager perceptions of agency performance on climate change.
AB  - An important precursor to the adoption of climate change adaptation strategies is
      to understand the perceived capacity to implement and operationalize such
      strategies. Utilizing an importance-performance analysis (IPA) evaluation
      framework, this article presents a comparative case study of federal and state
      land and natural resource manager perceptions of agency performance on factors
      influencing adaptive capacity in two U.S. regions (northern Colorado and
      southwestern South Dakota). Results revealed several important findings with
      substantial management implications. First, none of the managers ranked the
      adaptive capacity factors as a low priority. Second, managers held the perception
      that their agencies were performing either neutrally or poorly on most factors
      influencing adaptive capacity. Third, gap analysis revealed that significant
      improvements are required to facilitate optimal agency functioning when dealing
      with climate change-related management issues. Overall, results suggest that a
      host of institutional and policy-oriented (e.g., lack of clear mandate to adapt
      to climate change), financial and human resource (e.g., inadequate staff and
      financial resources), informational (e.g., inadequate research and monitoring
      programs) and contextual barriers (e.g., sufficient regional networks to mitigate
      potential transboundary impacts) currently challenge the efficient and effective
      integration of climate change into decision-making and management within agencies
      working in these regions. The IPA framework proved to be an effective tool to
      help managers identify and understand agency strengths, areas of concern,
      redundancies, and areas that warrant the use of limited funds and/or resource re
      allocation in order to enhance adaptive capacity and maximize management
      effectiveness with respect to climate change.

PMID- 23141869
TI  - An uncommon anatomic variant of the biliary tree in a potential liver donor.

PMID- 23141870
TI  - Comment to "Non-invasive assessment of hepatic fibrosis in a series of patients
      with Wilson's disease".

PMID- 23141871
TI  - Performance of Quantiferon((r)) for the diagnosis TB.
AB  - OBJECTIVES: The aim of the study was to evaluate the performance of Quantiferon
      Gold-In-Tube((r)) (QFN) for the diagnosis of tuberculosis (TB) during
      hospitalization in an infectious diseases department. PATIENTS AND METHODS: QFN
      was performed in 245 patients recently hospitalized for suspected TB. Subsets of
      patients underwent tuberculin skin tests (TST), and microbiological cultures were
      performed. RESULT: TB was diagnosed in 57 (23%) patients: pulmonary in 23 (40%),
      extrapulmonary in 16 (28%), and disseminated in 18 (32%). Seventeen (30%) of
      these TB patients were immunocompromised, including 12 with HIV infection. The
      sensitivity of QFN was 74%, its specificity 56%, its positive predictive value
      43% and negative predictive value (NPV) 92%. The sensitivity was similar in
      pulmonary and extrapulmonary TB but lower in disseminated TB, although not
      significantly so. The sensitivity was also lower (P=0.04) in immunocompromised
      patients. The specificity was lower in migrants than in native French patients
      (P=0.01), and lower in patients with a history of TB than in those without
      (P<0.001). Finally, combining culture with QFN significantly increased the
      sensitivity (P=0.008), and produced a higher NPV, as for the combination with
      TST, but not significantly different than with QFN alone. CONCLUSION: The
      performance of QFN was weak in this context, especially in subgroups at high risk
      for latent TB. However, combined negative results of QFN or TST and culture could
      be useful to rule out active TB.

PMID- 23141872
TI  - Screening for periodontopathogenic bacteria in severe chronic periodontitis in a
      Moroccan population.
AB  - OBJECTIVE: Bacteria play an important role in destructive periodontitis. The aim
      of this study was to screen for five highly pathogenic bacteria: Aggregatibacter
      actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia,
      Tannerella forsythia, and Treponema denticola, in Moroccan patients presenting
      with severe chronic periodontitis and to compare results with those of patients
      presenting with severe aggressive periodontitis. MATERIALS AND METHODS: Twenty
      three patients were included at the periodontology unit (School of dental
      medicine, University Mohammed 5 Souissi, Rabat, Morocco). The study was made on
      two groups: a test group of patients presenting with severe chronic
      periodontitis, and a control group of patients presenting with severe aggressive
      periodontitis. Plaque sampling was performed at the four deepest sites in each
      patient. The five studied bacteria were detected by PCR. RESULTS: The prevalence
      of A. actinomycetemcomitans and T. denticola was relatively low in the test group
      (13.3% and 20% respectively) compared with controls (37.5% and 37.5%
      respectively), without any statistical difference between the two groups.
      Furthermore, P. gingivalis and T. forsythia were frequently detected in both
      groups, without any statistical difference. CONCLUSION: The results of this
      preliminary study proved the presence of the studied periodontopathogenic
      bacteria both in severe chronic periodontitis and severe aggressive
      periodontitis.

PMID- 23141874
TI  - Avicenna's view on the prevention of thrombosis.

PMID- 23141873
TI  - Emerging themes in radical SAM chemistry.
AB  - Enzymes in the radical SAM (RS) superfamily catalyze a wide variety of reactions
      through unique radical chemistry. The characteristic markers of the superfamily
      include a [4Fe-4S] cluster coordinated to the protein via a cysteine triad motif,
      typically CX(3)CX(2)C, with the fourth iron coordinated by S-adenosylmethionine
      (SAM). The SAM serves as a precursor for a 5'-deoxyadenosyl radical, the central
      intermediate in nearly all RS enzymes studied to date. The SAM-bound [4Fe-4S]
      cluster is located within a partial or full triosephosphate isomerase (TIM)
      barrel where the radical chemistry occurs protected from the surroundings. In
      addition to the TIM barrel and a RS [4Fe-4S] cluster, many members of the
      superfamily contain additional domains and/or additional Fe-S clusters. Recently
      characterized superfamily members are providing new examples of the remarkable
      range of reactions that can be catalyzed, as well as new structural and
      mechanistic insights into these fascinating reactions.

PMID- 23141875
TI  - Long-term outcomes using a two-stent technique for the treatment of coronary
      bifurcations.
AB  - BACKGROUND: The crush and culotte are probably the most common two-stent
      techniques utilized for percutaneous coronary intervention (PCI) of complex
      bifurcation lesions. Long-term outcome associated with the utilization of these
      techniques is unknown. Our objective was to evaluate the long-term outcomes after
      bifurcation PCI utilizing these 2 techniques with a prospective PCI registry.
      METHODS: Between 11/1/2003 and 12/31/2007, 360 patients were treated with either
      crush (n=304) or culotte (n=56). Primary outcome was the occurrence of major
      adverse cardiac events (MACE) defined as the composite of death, myocardial
      infarction and target vessel revascularization. The major secondary outcome
      measure was MACE or occurrence of CCS Class >= 2 angina. RESULTS: After a median
      follow-up of 4.1 years (3.0-5.1), the occurrence of MACE was 23.9%. MACE or CCS
      Class >= 2 angina occurred in 27.5% of patients. Multivariable analysis revealed
      that creatinine clearance <60 ml/min (odds-ratio [OR]=1.71, 95% CI 1.08-2.71;
      p=0.022) and left ventricular ejection fraction <40% (OR=2.14, 95% CI 1.21-3.79;
      p=0.008) were independent predictors of MACE or CCS Class >= 2 angina. A larger
      main vessel reference diameter (OR=0.57, 95% CI 0.61-0.92), bifurcation angle
      <50% (OR=0.59, 95% CI 0.35-0.92) and a final kissing-balloon inflation (OR=0.75,
      95% CI 0.35-0.99) were associated with a lower risk of MACE or CCS Class >= 2
      angina. CONCLUSIONS: Application of the crush and culotte techniques is
      associated with efficacy and safety at long-term follow-up. Bifurcation angle, a
      final kissing balloon inflation and vessel reference diameter are important
      variables that impact on very long-term outcomes.

PMID- 23141876
TI  - Non-alcoholic fatty liver disease and cardiovascular risk.
AB  - The term "Non-alcoholic fatty liver disease" (NAFLD) covers a series of liver
      lesions similar to those induced by alcohol, but not caused by alcohol use. The
      importance of NAFLD lies in the high prevalence in Western societies and, from
      the point of view of the liver, in its progression from steatosis to cirrhosis
      and liver cancer. More recently, NAFLD has been found to be associated with lipid
      metabolism disorders, the deposition of fat outside of the adipocytes, insulin
      resistance and Metabolic Syndrome. Also attributed to NAFLD is a heightened
      systemic pro-inflammatory state, which accelerates arteriosclerosis, thereby
      increasing cardiovascular risk and associated cardiovascular events. Here we
      provide an update to the etiopathogenesis of NAFLD, its influence on
      cardiovascular disease, and the treatment options. 

PMID- 23141877
TI  - A new control scheme for PID load frequency controller of single-area and multi
      area power systems.
AB  - A new control structure with a tuning method to design a PID load frequency
      controller for power systems is presented. Initially, the controller is designed
      for single area power system, then it is extended to multi-area case. The
      controller parameters are obtained by expanding controller transfer function
      using Laurent series. Relay based identification technique is adopted to estimate
      power system dynamics. Robustness studies on stability and performance are
      provided, with respect to uncertainties in the plant parameters. The proposed
      scheme ensures that overall system remains asymptotically stable for all bounded
      uncertainties and for system oscillations. Simulation results show the
      feasibility of the approach and the proposed method improves the load disturbance
      rejection performance significantly even in the presence of the uncertainties in
      plant parameters.

PMID- 23141878
TI  - Reserve selection with land market feedbacks.
AB  - How to best site reserves is a leading question for conservation biologists.
      Recently, reserve selection has emphasized efficient conservation: maximizing
      conservation goals given the reality of limited conservation budgets, and this
      work indicates that land market can potentially undermine the conservation
      benefits of reserves by increasing property values and development probabilities
      near reserves. Here we propose a reserve selection methodology which optimizes
      conservation given both a budget constraint and land market feedbacks by using a
      combination of econometric models along with stochastic dynamic programming. We
      show that amenity based feedbacks can be accounted for in optimal reserve
      selection by choosing property price and land development models which
      exogenously estimate the effects of reserve establishment. In our empirical
      example, we use previously estimated models of land development and property
      prices to select parcels to maximize coarse woody debris along 16 lakes in Vilas
      County, WI, USA. Using each lake as an independent experiment, we find that
      including land market feedbacks in the reserve selection algorithm has only small
      effects on conservation efficacy. Likewise, we find that in our setting heuristic
      (minloss and maxgain) algorithms perform nearly as well as the optimal selection
      strategy. We emphasize that land market feedbacks can be included in optimal
      reserve selection; the extent to which this improves reserve placement will
      likely vary across landscapes.

PMID- 23141879
TI  - Bikunin and its emerging role in the modulation of tumor invasion and metastasis.

PMID- 23141880
TI  - Does health status affect perceptions of factors influencing dignity at the end
      of life?
AB  - CONTEXT: More people are surviving into old age, and chronic diseases tend to
      become more common with age. Ill health and disability can lead to concerns about
      loss of personal dignity. OBJECTIVES: To investigate whether health status
      affects the perceptions of factors influencing personal dignity at the end of
      life, and the relationship between those perceptions and sociodemographic
      characteristics. METHODS: A subsample (n=2282) of a large advance directives
      cohort study was used. Three different health status groups (good, moderate, and
      poor) were defined based on the Euroqol-5D and a question on whether they had an
      illness. For each health status group, we calculated the percentage of
      respondents who indicated the extent to which the items of the Patient Dignity
      Inventory would influence their dignity as (very) large. Logistic regression
      analyses were used to investigate the associations between the perceptions of
      factors influencing personal dignity and sociodemographics. RESULTS: The
      percentage of respondents who indicated the factors as having a (very) large
      influence on dignity at the end of life were not significantly different for the
      three health status groups, except for three physical items on symptoms, roles,
      and routines. Those items were significantly more influential on dignity for
      people with a poor health status. Gender, old age, having a partner, and having a
      belief or religion that is important to one's life were associated with an
      understanding of factors influential to dignity. CONCLUSION: Health status seems
      only to affect the perceptions of physical factors maintaining dignity at the end
      of life. This might suggest that the understanding of dignity will not
      substantially change as health status changes and may support starting advance
      care planning early.

PMID- 23141881
TI  - An open-label extension study to investigate the long-term safety and
      tolerability of THC/CBD oromucosal spray and oromucosal THC spray in patients
      with terminal cancer-related pain refractory to strong opioid analgesics.
AB  - CONTEXT: Chronic pain in patients with advanced cancer poses a serious clinical
      challenge. The Delta9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal
      spray (U.S. Adopted Name, nabiximols; Sativex((r))) is a novel cannabinoid
      formulation currently undergoing investigation as an adjuvant therapy for this
      treatment group. OBJECTIVES: This follow-up study investigated the long-term
      safety and tolerability of THC/CBD spray and THC spray in relieving pain in
      patients with advanced cancer. METHODS: In total, 43 patients with cancer-related
      pain experiencing inadequate analgesia despite chronic opioid dosing, who had
      participated in a previous three-arm (THC/CBD spray, THC spray, or placebo), two
      week parent randomized controlled trial, entered this open-label, multicenter,
      follow-up study. Patients self-titrated THC/CBD spray (n=39) or THC spray (n=4)
      to symptom relief or maximum dose and were regularly reviewed for safety,
      tolerability, and evidence of clinical benefit. RESULTS: The efficacy end point
      of change from baseline in mean Brief Pain Inventory-Short Form scores for "pain
      severity" and "worst pain" domains showed a decrease (i.e., improvement) at each
      visit in the THC/CBD spray patients. Similarly, the European Organization for
      Research and Treatment of Cancer Quality of Life Questionnaire-C30 scores showed
      a decrease (i.e., improvement) from baseline in the domains of insomnia, pain,
      and fatigue. No new safety concerns associated with the extended use of THC/CBD
      spray arose from this study. CONCLUSION: This study showed that the long-term use
      of THC/CBD spray was generally well tolerated, with no evidence of a loss of
      effect for the relief of cancer-related pain with long-term use. Furthermore,
      patients who kept using the study medication did not seek to increase their dose
      of this or other pain-relieving medication over time, suggesting that the
      adjuvant use of cannabinoids in cancer-related pain could provide useful benefit.

PMID- 23141883
TI  - Does measurement of event-related gamma-augmentation replace electrical
      stimulation via intracranial electrodes?

PMID- 23141882
TI  - Clinical significance and developmental changes of auditory-language-related
      gamma activity.
AB  - OBJECTIVE: We determined the clinical impact and developmental changes of
      auditory-language-related augmentation of gamma activity at 50-120 Hz recorded on
      electrocorticography (ECoG). METHODS: We analyzed data from 77 epileptic patients
      ranging 4-56 years in age. We determined the effects of seizure-onset zone,
      electrode location, and patient-age upon gamma-augmentation elicited by an
      auditory-naming task. RESULTS: Gamma-augmentation was less frequently elicited
      within seizure-onset sites compared to other sites. Regardless of age, gamma
      augmentation most often involved the 80-100 Hz frequency band. Gamma-augmentation
      initially involved bilateral superior-temporal regions, followed by left-side
      dominant involvement in the middle-temporal, medial-temporal, inferior-frontal,
      dorsolateral-premotor, and medial-frontal regions and concluded with bilateral
      inferior-Rolandic involvement. Compared to younger patients, those older than 10
      years had a larger proportion of left dorsolateral-premotor and right inferior
      frontal sites showing gamma-augmentation. The incidence of a post-operative
      language deficit requiring speech therapy was predicted by the number of resected
      sites with gamma-augmentation in the superior-temporal, inferior-frontal,
      dorsolateral-premotor, and inferior-Rolandic regions of the left hemisphere
      assumed to contain essential language function (r(2) = 0.59; p = 0.001; odds
      ratio = 6.04 [95% confidence-interval: 2.26-16.15]). CONCLUSIONS: Auditory
      language-related gamma-augmentation can provide additional information useful to
      localize the primary language areas. SIGNIFICANCE: These results derived from a
      large sample of patients support the utility of auditory-language-related gamma
      augmentation in presurgical evaluation.

PMID- 23141884
TI  - Test-retest reliability and stability of N400 effects: implications for the study
      of neuropsychiatric and cognitive disorders.

PMID- 23141885
TI  - Non-invasive high voltage electrical stimulation as a monitoring tool of nerve
      root function in lumbosacral surgery.
AB  - OBJECTIVE: To verify the safety and clinical use of non-invasive high-voltage
      electrical stimulation (HVES) in patients with compressive radiculopathy. To test
      the feasibility of HVES to survey nerve root function during lumbosacral surgery.
      METHODS: In 20 patients undergoing lumbosacral surgery for degenerative spinal
      diseases, compound muscle action potentials (CMAPs) evoked by maximal HVES were
      bilaterally recorded throughout surgery from L3 to S2 radicular territories. A
      preliminary study was performed in awake patients to rule out detrimental effects
      caused by HVES. RESULTS: Preoperative study confirmed the safety of HVES.
      Unexpectedly, a transient but significant remission of pain was observed after
      root stimulation. Intraoperative monitoring (IOM) was accomplished in all
      patients. HVES never hindered surgical procedures and never caused mechanical
      damage within the operatory field. In 4 patients acute, highly focal and
      reversible conduction failure was promptly detected by HVES in radicular
      territories congruent with the root manipulated at that moment. CONCLUSIONS: HVES
      is a safe and sensitive tool to monitor nerve root function in lumbosacral
      surgery. SIGNIFICANCE: The method is based on the assumption that any acute
      conduction failure occurring during surgery can be immediately and unambiguously
      detected by HVES if root stimulation is supramaximal and delivered rostral to the
      surgical level.

PMID- 23141886
TI  - Utility of normal tissue-to-tumor alpha/beta ratio when evaluating isodoses of
      isoeffective radiation therapy treatment plans.
AB  - PURPOSE: To achieve a better understanding of the effect of the number of
      fractions on normal tissue sparing for equivalent tumor control in radiation
      therapy plans by using equivalent biologically effective dose (BED) isoeffect
      calculations. METHODS AND MATERIALS: The simple linear quadratic (LQ) model was
      assumed to be valid up to 10 Gy per fraction. Using the model, we formulated a
      well-known mathematical equality for the tumor prescription dose and probed and
      solved a second mathematical problem for normal tissue isoeffect. That is, for a
      given arbitrary relative isodose distribution (treatment plan in percentages), 2
      isoeffective tumor treatment regimens (N fractions of the dose D and n fractions
      of the dose d) were denoted, which resulted in the same BED (corresponding to
      100% prescription isodose). Given these situations, the LQ model was further
      exploited to mathematically establish a unique relative isodose level, z (%), for
      the same arbitrary treatment plan, where the BED to normal tissues was also
      isoeffective for both fractionation regimens. RESULTS: For the previously stated
      problem, the relative isodose level z (%), where the BEDs to the normal tissue
      were also equal, was defined by the normal tissue alpha/beta ratio divided by the
      tumor alpha/beta times 100%. Fewer fractions offers a therapeutic advantage for
      those portions of the normal tissue located outside the isodose surface, z,
      whereas more fractions offer a therapeutic advantage for those portions of the
      normal tissue within the isodose surface, z. CONCLUSIONS: Relative isodose-based
      treatment plan evaluations may be useful for comparing isoeffective tumor
      regimens in terms of normal tissue effects. Regions of tissues that would benefit
      from hypofractionation or standard fractionation can be identified.

PMID- 23141887
TI  - Therapeutic approaches for hepatobiliary disorders with ursodeoxycholic acid and
      bile-acid derivatives.

PMID- 23141888
TI  - Primary biliary cirrhosis and bile acids.
AB  - The dihydroxylated bile acid ursodeoxycholic acid (UDCA) has now been regarded
      for 20 years as the standard treatment for primary biliary cirrhosis (PBC), a
      chronic cholestatic immune-mediated condition marked by progressive destruction
      of small intrahepatic bile ducts, impaired biliary secretion, hepatocellular
      retention of toxic endogenous bile acids and, ultimately, the development of
      fibrosis leading to cirrhosis that commonly requires liver transplantation. At
      first sight, it seems intriguing that a bile acid could be considered for use as
      a therapeutic agent in a bile-acid secretion disorder. Yet, in addition to its
      inherently greater hydrophilic nature and competitive effect on endogenous
      bileacid recycling, UDCA has indeed been demonstrated to be a potent post
      transcriptional secretagogue as well as a potential anti-inflammatory and anti
      apoptotic agent. While the combined glucocorticoid receptor/pregnane X receptor
      (PXR) agonist budesonide, in combinaison with UDCA, has been shown to exert
      additional beneficial effects in PBC, significant progress in understanding the
      regulatory mechanisms involved in bile-acid homeostasis has led to the
      identification of nuclear [farnesoid X receptor (FXR), PXR, peroxisome
      proliferator-activated receptor alpha (PPARalpha)] and membrane (the membrane G
      protein-coupled bile acid receptor TGR5) receptors as critical pharmacological
      targets for future therapeutic approaches. Encouraging data from recent
      experimental and phase-II studies tend to confirm that the FXR agonist
      obeticholic acid and the PPARalpha agonists bezafibrate and fenofibrate may be
      used as add-on therapies in PBC patients with inadequate responses to UDCA or
      even as alternative first-line agents. These results could mark the beginning of
      a new therapeutic era for PBC.

PMID- 23141889
TI  - Primary sclerosing cholangitis and bile acids.
AB  - Primary sclerosing cholangitis (PSC) is a rare and complex chronic cholestatic
      liver disease, and its management is hindered by a very poor understanding of its
      pathogenesis. Endogenous bile acids are likely to play a role either directly or
      indirectly in the pathogenesis and/or progression of PSC ('toxic
      bile'hypothesis). At present, no medical therapies have been proven to delay
      disease progression. Ursodeoxycholic acid (UDCA) is the agent that has received
      the most attention. Based on large randomized studies, it appears that UDCA at
      doses from 13 to 23 mg/kg/d has no proven benefit on survival, but is well
      tolerated and improves serum liver tests and surrogate markers of prognosis
      whereas, at higher doses (28-30 mg/kg/d), it is associated with a worsened
      outcome. However, except at very high doses and despite the controversies, many
      hepatologists still consider UDCA a reasonable treatment choice. Indeed, its use
      at dosages of 15-20 mg/kg/d has recently been approved for the treatment of PSC
      by the French National Health Authority. In addition, 24-nor-ursodeoxycholic
      acid, a side-chain-modified UDCA derivative, has shown promising results in
      animal models of PSC and is currently under investigation in humans.

PMID- 23141890
TI  - Progressive familial intrahepatic cholestasis.
AB  - Progressive familial intrahepatic cholestasis (PFIC) refers to a heterogeneous
      group of autosomal-recessive disorders of childhood that disrupt bile formation
      and present with cholestasis of hepatocellular origin. The exact prevalence
      remains unknown, but the estimated incidence varies between 1/50,000 and
      1/100,000 births. Three types of PFIC have been identified and associated with
      mutations in hepatocellular transport-system genes involved in bile formation.
      PFIC1 and PFIC2 usually appear in the first months of life, whereas onset of
      PFIC3 may arise later in infancy, in childhood or even during young adulthood.
      The main clinical manifestations include cholestasis, pruritus and jaundice. PFIC
      patients usually develop fibrosis and end-stage liver disease before adulthood.
      Serum gamma-glutamyltransferase (GGT) activity is normal in PFIC1 and PFIC2
      patients, but is elevated in PFIC3 patients. Both PFIC1 and PFIC2 are caused by
      impaired bile salt secretion due to defects in ATP8B1 encoding the FIC1 protein
      and in ABCB11 encoding bile salt export pump (BSEP) protein, respectively.
      Defects in ABCB4, encoding multidrug resistance 3 protein (MDR3), impair biliary
      phospholipid secretion, resulting in PFIC3. Diagnosis is based on clinical
      manifestations, liver ultrasonography, cholangiography and liver histology, as
      well as on specific tests to exclude other causes of childhood cholestasis. MDR3
      and BSEP liver immunostaining, and analysis of biliary lipid composition should
      help to select PFIC candidates for whom genotyping could be proposed to confirm
      the diagnosis. Antenatal diagnosis may be proposed for affected families in which
      a mutation has been identified. Ursodeoxycholic acid (UDCA) therapy should be
      initiated in all patients to prevent liver damage. In some PFIC1 and PFIC2
      patients, biliary diversion may also relieve pruritus and slow disease
      progression. However, most PFIC patients are ultimately candidates for liver
      transplantation. Monitoring of liver tumors, especially in PFIC2 patients, should
      be offered from the first year of life. Hepatocyte transplantation, gene therapy
      and specific targeted pharmacotherapy may represent alternative treatments in the
      future.

PMID- 23141891
TI  - Ursodeoxycholic acid and bile-acid mimetics as therapeutic agents for cholestatic
      liver diseases: an overview of their mechanisms of action.
AB  - Chronic cholestasis and liver inflammation are the two main pathophysiological
      components of the two major classes of disease - primary biliary cirrhosis (PBC)
      and primary sclerosing cholangitis (PSC) - leading to bile duct destruction and
      ultimately to cirrhosis and liver failure. Ursodeoxycholic acid (UDCA), initially
      introduced as a therapeutic approach to counteract the cholestatic components to
      PBC and PSC, was subsequently shown to exhibit unexpected anti-inflammatory and
      immunomodulatoty properties. The use of farnesoid X receptor (FXR) and TGR5
      agonists in various animal models have confirmed early observations indicating
      that bile acids are not only toxicants and inflammagens, but also repressors of
      innate and adaptive immunity. Obeticholic acid is a bile-acid mimetic, with no
      toxic or inflammagen behavior, that strongly activates FXR to combat the toxic
      effects of high concentrations of bile acid. Because UDCA is not an FXR agonist,
      its combination with obeticholic acid could be a promising tool for the treatment
      of PBC and PSC. In this overview, the biological properties of UDCA, NorUDCA and
      FXR agonists are highlighted, as well as their overlapping mechanisms of action
      in inflammatory biliary disorders.

PMID- 23141892
TI  - Low phospholipid-associated cholestasis and cholelithiasis.
AB  - Low phospholipid-associated cholestasis and cholelithiasis (LPAC) is a genetic
      disorder characterized by cholesterol gallbladder and intrahepatic stones. It is
      caused by a mutation of the gene ABCB4, which encodes the canalicular protein
      ABCB4/MDR3, a flippase that plays an essential role in the secretion of
      phosphatidylcholine into bile. Failure of this protein leads to secretion of bile
      that is poor in phospholipids and, hence, highly lithogenic, with potent
      detergent properties. This, in turn, leads to cholangiocyte luminal membrane
      injury and biliary lesions causing cholestasis. The diagnosis should be suspected
      when at least two of the following criteria are present: onset of symptoms before
      the age of 40 years; recurrence of biliary symptoms (biliary colic, jaundice,
      cholangitis, acute pancreatitis) after cholecystectomy; presence of echogenic
      foci within the liver indicative of intrahepatic stones or biliary sludge;
      previous episode(s) of intrahepatic cholestasis of pregnancy; and family history
      of gallstones in first-degree relatives. Intrahepatic stones can be demonstrated
      by ultrasonography with color Doppler examination, computed tomography and
      magnetic resonance imaging with magnetic resonance cholangiography, and the
      diagnosis confirmed by ABCB4 genotyping. Therapy with ursodeoxycholic acid offers
      prompt relief of symptoms and usually prevents complications. In some cases,
      however, surgery may be necessary.

PMID- 23141893
TI  - Treatment of NASH with ursodeoxycholic acid: pro.
AB  - Ursodeoxycholic acid (UDCA) is one of hepatologists'oldest friends, always ready
      to help, throughout the years, in numerous and various liver and biliary tract
      diseases. On paper, it has had an impeccable track record of cytoprotection in
      vitro and in vivo due to its pleiotropic effects on many pathways leading to cell
      injury. Most of its hepatoprotective effects demonstrated under experimental
      conditions proved able to counteract pathogenic mechanisms involved in the
      transition from steatosis to steatohepatitis, and early clinical studies
      suggested a potentially beneficial effect in non-alcoholic steatohepatitis (NASH)
      as well. Yet, only scant data on the efficacy of UDCA specifically in
      experimental models of steatosis/NASH are available, and the few available
      randomized controlled clinical studies have substantial methodological issues and
      are discussed in this review. Thus, at this point, there is not enough evidence
      to either confirm or reject the efficacy of UDCA in NASH, although many NASH
      patients clearly experience biochemical improvements with prolonged UDCA
      treatment. Also, a few new UDCA derivatives have shown promising activity in
      preclinical models and may be worth testing in clinical trials.

PMID- 23141894
TI  - Treatment of NASH with ursodeoxycholic acid: cons.
AB  - Non-alcoholic steatohepatitis (NASH) has a prevalence of 1% in Western countries.
      Its causes as well as its medical treatment are, to date, still debated.
      Recently, studies of agents suggested to have antiapoptotic, insulin-sensitizing
      or anti-inflammatory effects in patients with NASH have been conducted, one of
      which is ursodeoxycholic acid (UDCA), a tertiary bile acid. Between 1994 and
      2008, four prospective randomized, double-blind, placebo-controlled studies of
      the treatment of NASH with UDCA were conducted. The first study, by Lindor et
      al., compared the impact of 13-15 mg/kg/day of UDCA to a placebo. The second
      study by Dufour et al. had an additional third arm that administered combination
      therapy with UDCA and vitamin E. The third and fourth studies by Leuschner et al.
      and by Ratziu et al. evaluated high doses of UDCA at 25-35 mg/kg/day, and used
      liver biopsies and serum liver enzyme levels to evaluate the impact of UDCA. With
      the exception of Ratziu et al.'s study, which was lacking a second liver biopsy,
      none of these studies showed any significant differences in the treatment of NASH
      with UDCA compared with a placebo. However, Dufour et al. did observe a
      significant improvement of NASH with the combination (UDCA/VitE) vs placebo
      therapy, whereas UDCA monotherapy was not effective in the treatment of NASH.
      Nevertheless, the effects of other bile acids and combination therapies need to
      be explored.

PMID- 23141895
TI  - Chemoprevention of colorectal cancer with ursodeoxycholic acid: pro.
AB  - Colorectal cancer is the third and second most common cancer among men and women,
      respectively, in France. Interest in the chemoprevention of colorectal cancer has
      increased over the last two decades. Experimental data strongly suggest that
      ursodeoxycholic acid (UDCA) may have chemopreventative actions in colorectal
      cancer. UDCA is able to inhibit tumor development in azoxymethane and in dextran
      related colitis models. In high-risk populations such as subjects with previous
      colorectal adenoma removal or inflammatory bowel disease, five out of 10
      published studies suggested beneficial effects with UDCA on colonic
      carcinogenesis. In the azoxymethane model, UDCA inhibited tumor development by
      counteracting the tumor-promoting effects of secondary bile acids such as
      deoxycholic acid (DCA). The opposing effects of UDCA and DCA on lipid raft
      composition may be central to their effects on colonic tumorigenesis.
      Differential effects of DCA and UDCA on growth factor and inflammatory signals
      involved in colorectal carcinogenesis, such as epidermal growth factor receptor
      (EGFR) signaling and COX-2 expression, very likely mediate their opposing effects
      on colonic tumor promotion and tumor inhibition, respectively.

PMID- 23141896
TI  - Chemoprevention of colorectal cancer with ursodeoxycholic acid: cons.
AB  - Animal and human data suggest a relationship between bile acids, especially
      secondary bile acids, and colorectal cancer. Ursodeoxycholic acid, a synthetic
      bile acid, has been shown in animal and in vitro studies to reduce the risk of
      colonic dysplasia and cancer development. Human trials have focused on patients
      with history of adenoma, inflammatory bowel disease, primary sclerosing
      cholangitis, and primary biliary cirrhosis. Some studies suggest that
      ursodeoxycholic may reduce the colorectal cancer risk, but to date the studies
      are small, mostly retrospective, and lacking in solid evidence to support use of
      UDCA for colorectal cancer chemoprophylaxis.

PMID- 23141897
TI  - The transfection activity of R8-modified nanoparticles and siRNA condensation
      using pH sensitive stearylated-octahistidine.
AB  - Emerging evidence indicates that the efficiency of siRNA loading into an RNA
      induced silencing complex (RISC) is a major factor in gene silencing at low
      doses. In particular, the release of siRNA from components delivered to the
      cytoplasm could be a first step for achieving maximum gene knockdown effect in
      siRNA delivery vector. To test this hypothesis, we used a stearylated
      octahistidine (STR-H8) as a pH responsive polycation that facilitates the
      efficient release of siRNA into the cytoplasm, while a stearylated-octaarginine
      (STR-R8) was used as a conventional cationic polycation. As a fundamental
      structure, we used octaarginine (R8) and GALA, as a pH-sensitive fusogenic
      peptide, modified lipid envelope-type nanoparticles (R8/GALA-MEND(SUV)), as
      reported previously. When STR-H8/siRNA condensed complexes were loaded in the
      R8/GALA-MEND(SUV), the luciferase knockdown effect was significantly increased
      compared to STR-R8/siRNA condensed complexes in time and dose dependent manners.
      Quantification of the released siRNA from the condensed complexes demonstrated
      that only the STR-H8/siRNA released significant levels of siRNA at pH = 7.4, the
      pH of cytoplasmic, compared with STR-R8/siRNA condensed complexes. In addition,
      imaging studies indicated that STR-H8/siRNA facilitated siRNA release.
      Collectively, these data reveal the importance of the controlled release of siRNA
      to the cytoplasm.

PMID- 23141899
TI  - Adrenal ganglioneuroma: a diagnostic challenge.

PMID- 23141898
TI  - Fully defined in situ cross-linkable alginate and hyaluronic acid hydrogels for
      myocardial tissue engineering.
AB  - Despite recent major advances including reprogramming and directed cardiac
      differentiation of human cells, therapeutic application of in vitro engineered
      myocardial tissue is still not feasible due to the inability to construct
      functional large vascularized contractile tissue patches based on clinically
      applicable and fully defined matrix components. Typical matrices with preformed
      porous 3D structure cannot be applied due to the obvious lack of migratory
      capacity of cardiomyocytes (CM). We have therefore developed a fully defined in
      situ hydrogelation system based on alginate (Alg) and hyaluronic acid (HyA), in
      which their aldehyde and hydrazide-derivatives enable covalent hydrazone cross
      linking of polysaccharides in the presence of viable myocytes. By varying degrees
      of derivatization, concentrations and composition of blends in a modular system,
      mechanophysical properties of the resulting hydrogels are easily adjustable. The
      hydrogel allowed for the generation of contractile bioartificial cardiac tissue
      from CM-enriched neonatal rat heart cells, which resembles native myocardium. A
      combination of HyA and highly purified human collagen I led to significantly
      increased active contraction force compared to collagen, only. Therefore, our in
      situ cross-linking hydrogels represent a valuable toolbox for the fine-tuning of
      engineered cardiac tissue's mechanical properties and improved functionality,
      facilitating clinical translation toward therapeutic heart muscle reconstruction.

PMID- 23141900
TI  - Reliability of a new method for assessing tension and configuration of
      transobturator suburethral tapes using four-dimensional ultrasound.
AB  - We conducted this study to evaluate the intra- and interobserver reliability of a
      new method in assessing the tension and configuration of transobturator
      suburethral tape (TOT) at different tape points using 4-dimensional (4D)
      ultrasound. We randomly recruited 20 women following TOT procedures.
      Postoperative ultrasound datasets acquired during rest, straining, and coughing
      were digitally stored and analyzed offline by 2 independent and blinded
      investigators. The assessed parameters included axial tape-urethral distance,
      axial urethral central echolucent area, axial tape angle, and coronal tape angle
      at 5 equidistant tape points. For most parameters, the intraclass correlation
      coefficient and 95% confidence interval for intra- and interobserver reliability
      was higher than 0.70. 4D ultrasound can provide a quantitative method that meets
      minimal standards for reliability coefficients in assessing the tension and
      configuration of TOT. The reliability of the current method could be further
      evaluated when a whole new ultrasound examination was performed.

PMID- 23141901
TI  - Novel indices for left-ventricular dyssynchrony characterization based on highly
      automated segmentation from real-time 3-d echocardiography.
AB  - Cardiac resynchronization therapy (CRT) using a biventricular pacemaker is an
      invasive and expensive treatment option for left ventricular mechanical
      dyssynchrony (LVMD). The CRT candidate selection is a crucial issue due to the
      unreliability of the current standard CRT indicators. Real-time three-dimensional
      (3-D) echocardiography (RT3DE) provides four-dimensional (4-D) (3-D+time)
      information about the LV and is suitable for LVMD assessment. In this article,
      the complex left ventricle (LV) shape and motion of 50 RT3DE datasets are
      represented by novel 4-D descriptors - 4-D sphericity, volume and shape, from
      which novel indices were derived by principal component analysis (PCA) and
      subsequently analyzed by a support vector machine (SVM) classifier to assess
      their capability of LVMD characterization and CRT outcome prediction. These novel
      indices outperformed clinical indices and have promising capabilities in disease
      characterization and great potential in CRT outcome prediction. To enable
      efficient quantitative RT3DE analysis, a segmentation method was developed to
      combine the powers of active shape models and optimal graph search. Various
      aspects of the method were designed to handle varying RT3DE image quality among
      datasets and LV segments. An application with graphical user interface was
      developed to provide the user with simple and intuitive control. The developed
      method was robust to inter-observer variability and produced very good accuracy -
      3.2+/-1.1 mm absolute surface positioning error, <1 mm mean signed error and <5%
      mean volume difference. The computer method's classification performance was
      compared with the independent standard, showing that the 4-D shape modal indices
      were not only the most capable of all tested options when employed for disease
      characterization but also the least sensitive to segmentation imperfections.

PMID- 23141902
TI  - The increase of VEGF secretion from endothelial progenitor cells post ultrasonic
      VEGF gene delivery enhances the proliferation and migration of endothelial cells.
AB  - We investigated the feasibility of exogenous gene expression in endothelial
      progenitor cells (EPCs) through the use of ultrasonic microbubble transfection
      (UMT). EPCs originating from porcine peripheral blood were cultured in a medium
      containing constructed vascular endothelial growth factor (VEGF) pDNA followed by
      UMT. Simultaneously, comprehensive functional evaluations were conducted to
      investigate the effects of UMT of the VEGF gene on the EPCs. The results showed
      that UMT yielded significant VEGF protein expression. VEGF-containing supernatant
      originating from EPCs post UMT led to significantly enhanced activities of
      proliferation by more than 20% and migration by approximately 30% in human aortic
      endothelial cells. The duration of additional secretion of VEGF protein
      attributable to the exogenous VEGF gene in the EPCs post UMT lasted more than 96
      hours. In conclusion, UMT successfully delivers the VEGF gene into porcine EPCs,
      and VEGF-containing supernatant derived from EPCs post UMT enhances the
      proliferation and migration of human aortic endothelial cells.

PMID- 23141903
TI  - Enhancement effect of ultrasound-induced microbubble cavitation on branched
      polyethylenimine-mediated VEGF(165) transfection with varied N/P ratio.
AB  - One isoform of the vascular endothelial growth factor, VEGF(165), has been
      reported to be a dominant mediator and regulator of angiogenic process, which
      plays an important role in treating cardiovascular diseases and chronically
      ischemic wounds. Branched polyethylenimine (bPEI) has been widely used as a non
      viral delivery vector for gene therapy. Although bPEI-mediated DNA transfection
      efficiency can be raised by increasing the PEI nitrogen:DNA phosphate (N/P)
      ratio, cytotoxicity increases as well. In this study, the enhancement effect of
      microbubble inertial cavitation (IC) on bPEI-mediated VEGF(165) transfection was
      investigated, in an effort to optimize transfection efficiency using low N/P
      ratios. HEK 293T cells, mixed with bPEI:VEGF(165) complexes, were exposed to 1
      MHz ultrasound pulses. The results show that: (1) IC activity induced by
      microbubble destruction can be quantified as an IC "dose" (ICD) and will increase
      with increasing acoustic driving pressure; (2) larger sonoporation pores can be
      generated by increasing ICD; (3) the transfection efficiency can be enhanced by
      increasing ICD until reaching a saturation level; and (4) microbubble IC activity
      has less cytotoxicity than bPEI, although a combinatorial effect of microbubble
      IC activity and bPEI could be observed on cell viability. The results suggest
      that, with appropriate ultrasound parameters, it is possible to optimize bPEI
      mediated VEGF transfection efficiency using relatively low N/P ratios by
      employing ultrasound-induced microbubble inertial cavitation.

PMID- 23141904
TI  - Lack of correlation between cerebral vasomotor reactivity and flow-mediated
      dilation in subjects without vascular disease.
AB  - Cerebral vasomotor reactivity (CVR) represents the capability of cerebral vessels
      to modify their caliber in response to a stimulus. Impaired CVR is associated
      with an increased risk for ischemic events in patients with carotid disease.
      Endothelial dysfunction is considered an important pathogenic factor for
      atherosclerosis and can be noninvasively assessed by flow-mediated vasodilation
      (FMD) evaluation. We aimed to evaluate both CVR and FMD in patients without
      histories of vascular disease in order to define a possible correlation. FMD was
      measured as brachial artery flow and diameter changes induced by transient
      ischemia. CVR to hypercapnia was assessed in all subjects by means of a breath
      holding test and, in 20 subjects, by an additional CO(2) inhalation test. In 30
      healthy volunteers (60% women, mean age 56 +/- 6 years), CVR and FMD did not
      appear to be correlated (p = 0.444). A strong association between CO(2)-induced
      CVR and breath-holding index was observed (p < 0.001). CVR and FMD represent 2
      different modalities that evaluate vasomotor function. According to our data,
      they did not appear to correlate, probably due to physiologic differences between
      cerebral and peripheral vascular districts and the vasodilatory stimulus used.
      The carbon dioxide-induced CVR and breath-holding index appeared to be
      significantly associated.

PMID- 23141905
TI  - "Is immuno-expression of E-cadherin really a prognostic factor in head and neck
      cancer?".

PMID- 23141906
TI  - Initial clinical experience with the HeartWare left ventricular assist system: a
      single-center report.
AB  - BACKGROUND: The HeartWare ventricular assist device (HVAD) system (HeartWare
      International Inc, Framingham, MA) is a new centrifugal continuous-flow
      ventricular assist device. The aim of the present study is to review our
      institutional experience with this novel device. METHODS: We reviewed the files
      of 50 patients (39 men, 11 women) with a mean age of 50.6 +/- 11.8 years (range,
      19 to 70 years) who underwent HVAD implantation between July 2009 and November
      2011. Two patients underwent HeartWare BIVAD implantation. The underlying heart
      diseases were end-stage ischemic heart disease (n = 12), acute myocardial
      infarction (n = 9), dilated cardiomyopathy (n = 27) and acute myocarditis (n =
      2). Interagency Registry for Mechanically Assisted Circulatory Support
      (INTERMACS) profiles were level 1 (n = 11), 2 (n = 5), 3 (n = 10), and 4 (n =
      24). RESULTS: After a cumulative support duration of 11,086 days, Kaplan-Meier
      analysis revealed a survival of 82.0%, 77.9%, 75.5%, at 1, 12, and 24 months,
      respectively. Causes of early death were right heart failure (n = 4), multiorgan
      failure (n = 2), septic shock (n = 2), and major neurologic complications (n =
      4). One late death occurred due to a right heart failure. Comparison between
      patients operated on in cardiogenic shock (INTERMACS 1 and 2) and patients who
      underwent elective HVAD implantation (INTERMACS 3 and 4) revealed a survival of
      61.5% and 44.1% for the INTERMACS 1 and 2 group and 90.3% and 87.1% for the
      INTERMACS 3 and 4 group at 1 and 12 months, respectively (odds ratio, 4.67; p =
      0.003). One patient was weaned from the system after 2 years. Eleven patients
      (22%) were successfully bridged to transplantation. Mean time to transplantation
      was 209 days (range, 72 to 427 days). Posttransplant survival at the 1-year
      follow-up was 90.9% (11 patients). CONCLUSIONS: Our experience with HVAD shows
      satisfying results with an excellent posttransplantation survival. Moreover, the
      stratified survival based on the level of preoperative stability shows better
      outcomes in patients undergoing elective HVAD implantation.

PMID- 23141907
TI  - Differential case ascertainment in clinical registry versus administrative data
      and impact on outcomes assessment for pediatric cardiac operations.
AB  - BACKGROUND: Administrative datasets are often used to assess outcomes and quality
      of pediatric cardiac programs; however their accuracy regarding case
      ascertainment is unclear. We linked patient data (2004-2010) from the Society of
      Thoracic Surgeons Congenital Heart Surgery (STS-CHS) Database (clinical registry)
      and the Pediatric Health Information Systems (PHIS) database (administrative
      database) from hospitals participating in both to evaluate differential
      coding/classification of operations between datasets and subsequent impact on
      outcomes assessment. METHODS: Eight individual benchmark operations and the Risk
      Adjustment in Congenital Heart Surgery, version 1 (RACHS-1) categories were
      evaluated. The primary outcome was in-hospital mortality. RESULTS: The cohort
      included 59,820 patients from 33 centers. There was a greater than 10% difference
      in the number of cases identified between data sources for half of the benchmark
      operations. The negative predictive value (NPV) of the administrative (versus
      clinical) data was high (98.8%-99.9%); the positive predictive value (PPV) was
      lower (56.7%-88.0%). Overall agreement between data sources in RACHS-1 category
      assignment was 68.4%. These differences translated into significant differences
      in outcomes assessment, ranging from an underestimation of mortality associated
      with truncus arteriosus repair by 25.7% in the administrative versus clinical
      data (7.01% versus 9.43%; p = 0.001) to an overestimation of mortality associated
      with ventricular septal defect (VSD) repair by 31.0% (0.78% versus 0.60%; p =
      0.1). For the RACHS-1 categories, these ranged from an underestimation of
      category 5 mortality by 40.5% to an overestimation of category 2 mortality by
      12.1%; these differences were not statistically significant. CONCLUSIONS: This
      study demonstrates differences in case ascertainment between administrative and
      clinical registry data for children undergoing cardiac operations, which
      translated into important differences in outcomes assessment.

PMID- 23141908
TI  - Statin treatment of children with familial hypercholesterolemia--trying to
      balance incomplete evidence of long-term safety and clinical accountability: are
      we approaching a consensus?
AB  - In the heterozygous form of familial hypercholesterolemia (FH), blood
      concentrations of low-density lipoprotein cholesterol (LDL-C) are elevated two to
      three times above the normal range since birth, and cause strongly elevated risk
      of premature coronary artery disease (CAD). There is no evidence that statin
      therapy is unsafe in FH children, and it has not been associated with clinically
      significant changes in measures of growth or maturation, liver enzymes, serum
      creatine kinase, or incidence of myopathy. However, the opinions among
      clinicians, and between countries, about the age at which statin therapy should
      be initiated in FH children vary. This review attempts to critically examine the
      available data, so that clinically the most appropriate age of initiating statin
      treatment in FH children as a preventive measure for future CAD could be
      established.

PMID- 23141909
TI  - Design and synthesis of novel bis-thiazolone derivatives as micromolar CDC25
      phosphatase inhibitors: effect of dimerisation on phosphatase inhibition.
AB  - CDC25 phosphatases are involved in deregulated cell cycle progression and tumor
      development with poor prognosis. Among the most potent CDC25 inhibitors,
      quinonoid-based derivatives have been extensively studied. Dimerisation of
      heterocyclic quinones has led to IRC-083864, a bis-quinone compound with
      increased CDC25B inhibitory activity. Thirty-one bis-thiazolone derivatives were
      synthesized and assayed for CDC25 inhibitory activity. Most of the dimers
      displayed enhanced inhibitory activities with micromolar IC(50) values lower than
      that observed for each thiazolone scaffold separately. Moreover, most of these
      compounds were selective CDC25 inhibitors. Dimer 40 showed an IC(50) value of 2.9
      MUM and could inhibit CDC25 activity without generating reactive oxygen species
      which is likely to occur with quinone-based inhibitors. Molecular docking studies
      suggested that the dimers could bind simultaneously to the active site and the
      inhibitor binding pocket.

PMID- 23141910
TI  - New diterpene furanoids from the Antarctic lichen Huea sp.
AB  - In the course of ongoing research on protein tyrosine phosphatase 1B (PTP1B)
      inhibitory compounds from Antarctic lichens, four new diterpene furanoids,
      hueafuranoids A-D (1-4) have been isolated from the MeOH extract of Antarctic
      lichen Huea sp. by various chromatographic methods. The structures of these
      compounds were elucidated by analysis of NMR and MS data, and comparing their
      spectral data with those in the literature. Compound 1 showed inhibitory activity
      against therapeutically targeted protein, PTP1B with an IC(50) value of 13.9 MUM.
      The kinetic analysis of PTP1B inhibition by hueafuranoid A (1) suggested that the
      diterpene furanoids encountered in this study inhibited PTP1B activity in a non
      competitive manner.

PMID- 23141911
TI  - Heteroaryl urea inhibitors of fatty acid amide hydrolase: structure-mutagenicity
      relationships for arylamine metabolites.
AB  - The structure-activity relationships for a series of heteroaryl urea inhibitors
      of fatty acid amide hydrolase (FAAH) are described. Members of this class of
      inhibitors have been shown to inactivate FAAH by covalent modification of an
      active site serine with subsequent release of an aromatic amine from the urea
      electrophile. Systematic Ames II testing guided the optimization of urea
      substituents by defining the structure-mutagenicity relationships for the
      released aromatic amine metabolites. Potent FAAH inhibitors were identified
      having heteroaryl amine leaving groups that were non-mutagenic in the Ames II
      assay.

PMID- 23141912
TI  - Design, synthesis and pharmacological evaluation of 4-(piperazin-1-yl methyl)-N1
      arylsulfonyl indole derivatives as 5-HT6 receptor ligands.
AB  - 4-(Piperazin-1-yl methyl)-N(1)-arylsulfonyl indole derivatives were designed and
      synthesized as 5-HT(6) receptor (5-HT(6)R) ligands. The lead compound 6a, from
      this series shows potent in vitro binding affinity, good PK profile, no CYP
      liabilities and activity in animal models of cognition.

PMID- 23141913
TI  - Discovery of a novel class of zwitterionic, potent, selective and orally active
      S1P1 direct agonists.
AB  - Amido-1,3,4-thiadiazoles have been identified as a novel structural class of
      potent and selective sphingosine-1-phosphate receptor subtype 1 agonists.
      Starting from a micromolar HTS hit with the help of an in-house homology model,
      robust structural-activity relationships were developed to yield compounds with
      good selectivity and excellent in vivo efficacy in rat models.

PMID- 23141915
TI  - Synthesis of C3-arylated-3-deazauridine derivatives with potent anti-HSV-1
      activities.
AB  - A series of 3-deazauridines (3-DU) analogues were synthesized and evaluated in
      vitro for their antiherpetic activity against HSV-1 on Vero cell lines by cell
      viability. A first campaign of tests suggested that C3-arylated-3-DU derivatives
      could constitute a novel family of antiherpetic agents. A second campaign of
      biological evaluations led to the discovery of two potent anti-HSV-1 agents with
      comparable activity than acyclovir.

PMID- 23141914
TI  - Discovery of a novel series of benzimidazole derivatives as diacylglycerol
      acyltransferase inhibitors.
AB  - A novel series of benzimidazole derivatives was prepared and evaluated for their
      diacylglycerol acyltransferase (DGAT) inhibitory activity using microsome from
      rat liver. Among the newly synthesized compounds, furfurylamine containing
      benzimidazole carboxamide 10j showed the most potent DGAT inhibitory effect
      (IC(50)=4.4 MUM) and inhibited triglyceride formation in HepG2 cells.
      Furthermore, compound 10j reduced body weight gain of Institute of Cancer
      Research mice on a high-fat diet and decreased levels of total triglyceride,
      total cholesterol, and LDL-cholesterol in the blood accompanied with a
      significant increase in HDL-cholesterol level.

PMID- 23141916
TI  - Atom-based enumeration: new eribulin analogues with low susceptibility to P
      glycoprotein-mediated drug efflux.
AB  - A series of eribulin analogues was evolved in silico through iterative atom-based
      enumeration employing a genetic algorithm-derived survival function to minimize
      predicted PgP-mediated drug efflux. Representatives of the virtual series were
      subsequently synthesized in the laboratory and tested in vitro for PgP
      susceptibility. These new computer-inspired derivatives were found to exhibit
      high cell growth inhibitory activity and to be among the least sensitive to P
      glycoprotein-mediated drug efflux in the eribulin series, thereby validating this
      approach to in silico molecular design.

PMID- 23141917
TI  - Expression of corticosteroid binding globulin in the rat olfactory system.
AB  - Glucocorticoids are known to act on the olfactory system although their mode of
      action is still unclear since nuclear glucocorticoid receptors are mostly absent
      in the olfactory mucosa. In this study we used immunocytochemistry, in situ
      hybridization, and RT-PCR to study the expression and distribution of
      corticosteroid binding globulin (CBG) in the rat olfactory system. Mucosal goblet
      cells could be immunostained for CBG. Nasal secretion contained measurable
      amounts of CBG suggesting that CBG is liberated. CBG immunoreactivity was
      localized in many of the basal cells of the olfactory mucosa, while mature
      sensory cells contained CBG only in processes as determined by double
      immunostaining with the olfactory marker protein OMP. This staining was most
      pronounced in the vomeronasal organ (VNO). The appearance of CBG in the non
      sensory and sensory parts of the VNO and in nerve terminals in the accessory bulb
      indicated axonal transport. Portions of the periglomerular cells, the mitral
      cells and the tufted cells were also CBG positive. CBG encoding transcripts were
      confirmed by RT-PCR in homogenates of the olfactory mucosa and VNO. Olfactory CBG
      may be significant for uptake, accumulation and transport of glucocorticoids,
      including aerosolic cortisol.

PMID- 23141918
TI  - A novel vector control device in horizontal bone transport.

PMID- 23141919
TI  - Which central line insertion site is the least prone to infection?

PMID- 23141920
TI  - Ultrasound-guided peripheral intravenous access program is associated with a
      marked reduction in central venous catheter use in noncritically ill emergency
      department patients.
AB  - STUDY OBJECTIVE: We examine the central venous catheter placement rate during the
      implementation of an ultrasound-guided peripheral intravenous access program.
      METHODS: We conducted a time-series analysis of the monthly central venous
      catheter rate among adult emergency department (ED) patients in an academic urban
      ED between 2006 and 2011. During this period, emergency medicine residents and ED
      technicians were trained in ultrasound-guided peripheral intravenous access. We
      calculated the monthly central venous catheter placement rate overall and
      compared the central venous catheter reduction rate associated with the
      ultrasound-guided peripheral intravenous access program between noncritically ill
      patients and patients admitted to critical care. Patients receiving central
      venous catheters were classified as noncritically ill if admitted to telemetry or
      medical/surgical floor or discharged home from the ED. RESULTS: During the study
      period, the ED treated a total of 401,532 patients, of whom 1,583 (0.39%)
      received a central venous catheter. The central venous catheter rate decreased by
      80% between 2006 (0.81%) and 2011 (0.16%). The decrease in the rate was
      significantly greater among noncritically ill patients (mean for telemetry
      patients 4.4% per month [95% confidence interval {CI} 3.6% to 5.1%], floor
      patients 4.8% [95% CI 4.2% to 5.3%], and discharged patients 7.6% [95% CI 6.2% to
      9.1%]) than critically ill patients (0.9%; 95% CI 0.6% to 1.2%). The proportion
      of central venous catheters that were placed in critically ill patients increased
      from 34% in 2006 to 81% in 2011 because fewer central venous catheterizations
      were performed in noncritically ill patients. CONCLUSION: The ultrasound-guided
      peripheral intravenous access program was associated with reductions in central
      venous catheter placement, particularly in noncritically ill patients. Further
      research is needed to determine the extent to which such access can replace
      central venous catheter placement in ED patients with difficult vascular access.

PMID- 23141921
TI  - Systemic absorption of mitomycin-C when used in refractive surgery.
AB  - PURPOSE: To determine whether corneal topical application of mitomycin-C (MMC)
      results in measurable plasma levels of systemic absorption. SETTING: Madigan Army
      Medical Center, Refractive Surgery Center, Fort Lewis, Washington, and Micro
      Constants Laboratory, San Diego, California, USA. DESIGN: Case-control study.
      METHODS: The study comprised male and female active-duty soldiers having excimer
      laser photorefractive keratectomy with MMC. Patients who met inclusion criteria
      were asked to provide a blood sample immediately after being treated with MMC 0.2
      mg/mL (0.02%) for 30 seconds. Human plasma samples were evaluated by liquid
      chromatography mass spectrometry to determine whether MMC was present. RESULTS:
      Thirty samples were submitted for evaluation. There was zero detection of MMC in
      the submitted samples. The quantifiable limit was greater than 10.0 ng/mL. All
      samples were below this. CONCLUSIONS: In this study of 30 patients with topical
      application of MMC for refractive surgery, there was no measurable evidence of
      systemic absorption. Although systemic absorption has been found with use in
      larger quantities, it was not known whether MMC toxicity concerns could be
      extrapolated to the refractive surgery population. This information allows
      counseling of patients on the extremely low likelihood of systemic absorption or
      toxicity following current techniques for refractive surgery. FINANCIAL
      DISCLOSURE: No author has a financial or proprietary interest in any material or
      method mentioned.

PMID- 23141922
TI  - C-reactive protein: a biomarker of survival in patients with localized upper
      tract urothelial carcinoma treated with radical nephroureterectomy.
AB  - BACKGROUND AND OBJECTIVE: Serum C-reactive protein (CRP) is one particular marker
      of systemic inflammation, and an elevated CRP level is associated with poor
      outcome in various malignancies. While the clinical value of CRP levels in upper
      tract urothelial carcinoma (UTUC) has not yet been fully evaluated, we
      investigated the impact of CRP elevation as a biomarker of patient prognosis in
      UTUC. MATERIALS AND METHODS: A total of 183 patients who underwent radical
      nephroureterectomy (RNU) for localized UTUC (pTa-4N0M0) were identified between
      1993 and 2009. The associations between the levels of serum CRP and patient
      outcome were analyzed. RESULTS: Thirty-three patients experienced disease
      recurrence, and 28 died of the disease during the median follow-up period of 39
      months. Using the defined cutoff level of CRP >0.5 mg/dl as elevated,
      preoperative CRP (pre-CRP) levels were elevated in 42 patients (23.0%). Kaplan
      Meier curves revealed that subsequent tumor recurrences and worse cancer-specific
      survival could be significantly predicted in the elevated pre-CRP group. The 5
      year recurrence-free survival rate was 63.6% in the elevated pre-CRP group and
      83.4% in their counterparts (P < 0.001), and the 5-year cancer-specific survival
      rate was 64.7% in the elevated pre-CRP group and 84.3% in their counterparts (P =
      0.001). Multivariate analysis revealed that elevated pre-CRP, in addition to
      pathologic T stage, was an independent risk factor for subsequent disease
      recurrence (P = 0.003, hazard ration (HR) = 2.83), and the decrease in cancer
      specific survival (P = 0.012, HR = 2.65). In subgroup analysis using patients
      with pT3 tumors or greater, multivariate analysis also showed that elevated pre
      CRP was an independent risk factor for a decrease in both recurrence-free and
      cancer-specific survival. CONCLUSIONS: Pre-CRP level was an independent predictor
      of patient survival in localized advanced UTUC. Patients with pre-CRP >0.5 mg/dl
      were strongly predicted to have worse prognostic outcomes following RNU. Due to
      its low cost and easy accessibility, CRP may be a useful biomarker for localized
      UTUC.

PMID- 23141923
TI  - A functional approach reveals community responses to disturbances.
AB  - Understanding the processes shaping biological communities under multiple
      disturbances is a core challenge in ecology and conservation science.
      Traditionally, ecologists have explored linkages between the severity and type of
      disturbance and the taxonomic structure of communities. Recent advances in the
      application of species traits, to assess the functional structure of communities,
      have provided an alternative approach that responds rapidly and consistently
      across taxa and ecosystems to multiple disturbances. Importantly, trait-based
      metrics may provide advanced warning of disturbance to ecosystems because they do
      not need species loss to be reactive. Here, we synthesize empirical evidence and
      present a theoretical framework, based on species positions in a functional
      space, as a tool to reveal the complex nature of change in disturbed ecosystems.

PMID- 23141924
TI  - FcgammaRIIa ligation induces platelet hypersensitivity to thrombotic stimuli.
AB  - Platelets are known for their important role in hemostasis, however their
      significance in other functions, including inflammation and infection, are
      becoming more apparent. Patients with systemic lupus erythematosus (SLE) are
      known to have circulating IgG complexes in their blood and are highly susceptible
      to thrombotic events. Because platelets express a single receptor for IgG, we
      tested the hypothesis that ligation of this receptor (FcgammaRIIa) induces
      platelet hypersensitivity to thrombotic stimuli. Platelets from SLE patients were
      considerably more sensitive to thrombin compared to healthy volunteers, and this
      correlated with elevated levels of surface IgG on SLE platelets. To test whether
      FcgammaRIIa ligation stimulated thrombin hypersensitivity, platelets from healthy
      volunteers were incubated with buffer or heat-aggregated IgG, then stimulated
      with increasing concentrations of thrombin. Interestingly, heat-aggregated IgG
      stimulated platelets, but not buffer-treated platelets, were hypersensitive to
      thrombin, and hypersensitivity was blocked by an anti-FcgammaRIIa monoclonal
      antibody (mAb). Thrombin hypersensitivity was not due to changes in thrombin
      receptor expression (GPIbalpha or PAR1) but is dependent on activation of shared
      signaling molecules. These observations suggest that ligation of platelet
      FcgammaRIIa by IgG complexes induces a hypersensitive state whereby small changes
      in thrombotic stimuli may result in platelet activation and subsequent vascular
      complications such as transient ischemic attacks or stroke.

PMID- 23141925
TI  - Platelet-derived growth factor (PDGF)-C neutralization reveals differential roles
      of PDGF receptors in liver and kidney fibrosis.
AB  - Platelet-derived growth factors (PDGF) are key mediators of organ fibrosis. We
      investigated whether PDGF-C(-/-) mice or mice treated with neutralizing PDGF-C
      antibodies are protected from bile duct ligation-induced liver fibrosis, and we
      compared the effects with those of PDGF-C deficiency or neutralization on kidney
      fibrosis induced by unilateral ureteral obstruction. Unexpectedly, and in
      contrast to kidney fibrosis, PDGF-C deficiency or antagonism did not protect from
      liver fibrosis or functional liver impairment. Furthermore, the hepatic
      infiltration of monocytes/macrophages/dendritic cells and chemokine mRNA
      expression (CC chemokine ligand [CCL]5, CCL2, and CC chemokine receptor 2 [CCR2])
      remained unchanged. Transcript expression of PDGF ligands increased in both liver
      and kidney fibrosis and was not affected by neutralization of PDGF-C. In kidney
      fibrosis, PDGF-C deficiency or antagonism led to reduced expression and signaling
      of PDGF-receptor (R)-alpha- and PDGFR-beta-chains. In contrast, in liver fibrosis
      there was either no difference (PDGF-C(-/-) mice) or even an upregulation of
      PDGFR-beta and signaling (anti-PDGF-C group). Finally, in vitro studies in portal
      myofibroblasts pointed to a predominant role of PDGF-B and PDGF-D signaling in
      liver fibrosis. In conclusion, our study revealed significant differences between
      kidney and liver fibrosis in that PDGF-C mediates kidney fibrosis, whereas
      antagonism of PDGF-C in liver fibrosis appears to be counteracted by significant
      upregulation and increased PDGFR-beta signaling. PDGF-C antagonism, therefore,
      may not be effective to treat liver fibrosis.

PMID- 23141926
TI  - PGC-1alpha regulates normal and pathological angiogenesis in the retina.
AB  - Neovascular diseases of the eye are the most common causes of blindness
      worldwide. The mechanisms underlying pathological neovascularization in the
      retina remain incompletely understood. PGC-1alpha is a transcriptional
      coactivator that plays a central role in the regulation of cellular metabolism.
      In skeletal muscle, PGC-1alpha induces VEGFA expression and powerfully promotes
      angiogenesis, suggesting a similar role in other tissues. This study investigates
      the role of PGC-1alpha during normal and pathological vascularization in the
      retina. We show that PGC-1alpha induces the expression of VEGFA in numerous
      retinal cells, and that PGC-1alpha expression is strongly induced during
      postnatal retinal development, coincident with VEGFA expression and angiogenesis.
      PGC-1alpha(-/-) mice have a significant reduction of early retinal vascular
      outgrowth, and reduced density of capillaries and number of main arteries and
      veins as adults. In the oxygen-induced retinopathy model of retinopathy of
      prematurity, PGC-1alpha expression is dramatically induced in the inner nuclear
      layer of the retina, suggesting that PGC-1alpha drives pathological
      neovascularization. In support of this, PGC-1alpha(-/-) mice subjected to oxygen
      induced retinopathy had decreased expression of VEGFA and were protected against
      pathological neovascularization. These results demonstrate that PGC-1alpha
      regulates VEGFA in the retina and is required for normal vessel development and
      for pathological neovascularization. The data highlight PGC-1alpha as a novel
      target in the treatment of neovascular diseases of the eye.

PMID- 23141927
TI  - Toll-like receptor 4 signaling augments transforming growth factor-beta
      responses: a novel mechanism for maintaining and amplifying fibrosis in
      scleroderma.
AB  - Because recent studies implicate Toll-like receptors (TLRs) in the pathogenesis
      of fibrosis, we sought to investigate the in vitro and in vivo role and mechanism
      of TLR4-mediated fibroblast responses in fibrogenesis. We found that TLR4 was
      constitutively expressed, and accumulation of endogenous TLR4 ligands
      significantly elevated, in lesional skin and lung tissues from patients with
      scleroderma. Activation of TLR4 signaling in explanted fibroblasts resulted in
      enhanced collagen synthesis and increased expression of multiple genes involved
      in tissue remodeling and extracellular matrix homeostasis. Moreover, TLR4
      dramatically enhanced the sensitivity of fibroblasts to the stimulatory effect of
      transforming growth factor-beta1. These profibrotic responses were abrogated by
      both genetic and pharmacological disruption of TLR4 signaling in vitro, and skin
      fibrosis induced by bleomycin in vivo was attenuated in mice harboring a mutated
      TLR4. Activation of TLR4 in fibroblasts augmented the intensity of canonical Smad
      signaling, and was accompanied by suppression of anti-fibrotic microRNA
      expression. Together, these results suggest a novel model to account for
      persistent fibrogenesis in scleroderma, in which activation of fibroblast TLR4
      signaling, triggered by damage-associated endogenous TLR4 ligands, results in
      augmented transforming growth factor-beta1 sensitivity with increased matrix
      production and progressive connective tissue remodeling. Under these conditions,
      fibroblast TLR4 serves as the switch for converting self-limited tissue repair
      into intractable fibrosis.

PMID- 23141928
TI  - Long intergenic noncoding RNA HOTAIR is overexpressed and regulates PTEN
      methylation in laryngeal squamous cell carcinoma.
AB  - Homeobox (HOX) transcript antisense RNA (HOTAIR) is a long intergenic noncoding
      RNA (lincRNA) that is significantly overexpressed in breast and hepatocellular
      cancers. It remains unclear, however, whether HOTAIR plays an oncogenic role in
      human laryngeal squamous cell cancer (LSCC). We therefore investigated the
      expression and functional role of HOTAIR in LSCC. HOTAIR levels were
      significantly higher in LSCC than in corresponding adjacent non-neoplastic
      tissues, and patients with poor histological grade or advanced clinical stage had
      higher HOTAIR expression. Log-rank test showed a significant association between
      high levels of HOTAIR and poor prognosis in LSCC patients. Multivariate Cox
      analysis suggested that HOTAIR is an independent prognostic factor of LSCC. siRNA
      mediated knockdown of HOTAIR led to reduced invasion and increased apoptosis of
      Hep-2 cells in vitro and significantly reduced growth of LSCC xenograft tumors in
      mice. Moreover, PTEN methylation was significantly reduced in Hep-2 cells
      depleted of HOTAIR. Taken together, these results suggest that the oncogenic role
      of HOTAIR in LSCC is related to promotion of PTEN methylation. HOTAIR could serve
      as a marker for LSCC prognosis and a potential target for therapeutic
      intervention.

PMID- 23141929
TI  - A controlled case study of the relationship between environmental risk factors
      and apoptotic gene polymorphism and lumbar disc herniation.
AB  - To explore the etiologic role of apoptosis-related genes, environmental risk
      factors, and their interaction in the occurrence of lumbar disk herniation (LDH),
      a controlled case study was performed with 128 LDH patients and 132 age- and sex
      matched controls. Matrix-assisted laser desorption/ionization, time-of-flight
      mass spectrometry assay was used to analyze the genotype of nine polymorphism
      sites in three genes, including Fas -1377G/A rs2234767, Fas -670G/A rs1800682,
      Fas rs2147420, Fas rs2296603, Fas rs7901656, Fas rs1571019, Fas ligand (FasL) 
      844C/T rs763110, caspase 9 (CASP9) -1263A>G rs4645978, and CASP9 -712C>T
      rs4645981. The patients and controls showed similar age and sex, but had
      significant differences in lumbar load, bed type, amateur sports, and leisure
      activities (P < 0.05). The correlation analysis revealed that polymorphism of
      FasL -844C/T (rs763110) and CASP9 -1263A>G (rs4645978) had a significant
      correlation with LDH, indicating that the genotypes of FasL -844C/T TT and CASP9 
      1263A>G GG are probably high-risk genotypes for LDH. The results of environment
      gene interaction analysis revealed that, in LDH, the interaction of the FasL 
      844TT genotype and level III to IV lumbar load was consistent with the
      ultramultiplying model, and the interaction of the CASP9 rs4645978 GG genotype
      and level III to IV lumbar load was consistent with the submultiplicative model.
      Therefore, the risk of LDH was determined by both environmental and genetic risk
      factors, and the mechanisms of interactions between different genotypes and
      environmental factors also differed.

PMID- 23141930
TI  - Cytomegalovirus DNA detection in dried blood spots and perilymphatic fluids from
      pediatric and adult cochlear implant recipients with prelingual deafness.
AB  - BACKGROUND: Congenital cytomegalovirus (CMV) infection is the leading cause of
      non-genetic congenital hearing loss. The contribution of congenital CMV to
      prelingual deafness and the pathophysiology is largely unknown. OBJECTIVE: (1) To
      analyze the prevalence of congenital CMV among cochlear implant (CI) recipients
      with prelingual deafness. (2) To genotype CMV present in dried blood spots (DBS)
      and in the inner ear years after birth. STUDY DESIGN: Children and adults with
      prelingual deafness who received a CI in 2010-2011 were included prospectively.
      Perilymphatic fluids were collected during CI surgery and, in the pediatric
      cases, DBS were retrieved for CMV DNA detection. Furthermore, a cohort of
      children with prelingual deafness who received a CI between 2003 and 2008 were
      included retrospectively. CMV detection in DBS and perilymph was followed by gB
      and gH genotyping. RESULTS: Seventysix pediatric CI recipients were included.
      Seventy DBS were tested for CMV DNA, resulting in a prevalence of congenital CMV
      of 14% (10/70). Perilymphatic fluid was available from 29 pediatric CI
      recipients. One perilymph fluid, of a 21-month old girl with congenital CMV,
      asymptomatic at birth, was CMV DNA positive. The CMV strain in the perilymph was
      genotypically identical to the strain present in her DBS (gB1/gH2). Perilymph
      samples from 21 adult CI recipients were CMV DNA negative. CONCLUSIONS: Our study
      stresses the important contribution of congenital CMV among pediatric CI
      recipients. Furthermore, our genotyping data support the hypothesis that CMV
      related hearing loss is associated with ongoing viral replication in the inner
      ear up to years after birth.

PMID- 23141931
TI  - [Transient obstructive hydrocephalus following traumatic brain injury].

PMID- 23141932
TI  - Sleep duration versus sleep insufficiency as predictors of cardiometabolic health
      outcomes.
AB  - OBJECTIVE: The objective of the present study was to investigate the relationship
      between sleep insufficiency and sleep duration, particularly regarding negative
      cardiometabolic health outcomes already considered to be affected by reduced
      sleep time. METHODS: A total of N=30,934 participants from the 2009 Behavioural
      Risk Factor Surveillance System (BRFSS) answered questions about their sleep
      duration as well as subjective feelings of sleep insufficiency. Outcomes included
      body mass index (BMI), obesity (BMI >= 30kgm(-2)) and history of hypertension,
      diabetes, hypercholesterolaemia, heart attack and stroke. Linear and logistic
      regression models examined whether cardiometabolic outcomes were associated with
      (1) sleep duration alone, (2) sleep insufficiency alone and (3) the combined
      effect of sleep duration and sleep insufficiency. RESULTS: Results indicated
      that, when examined alone, sleep duration <5h (versus 7h) was related to BMI
      (B=2.716, p<0.01), obesity (B=2.080, p<0.000001), diabetes (B=3.162, p<0.000001),
      hypertension (B=2.703, p<0.000001), hypercholesterolaemia (B=1.922, p<0.00001),
      heart attack (B=4.704, p<0.000001) and stroke (B=4.558, p<0.000001), and sleep
      insufficiency (days per week, continuous) was related to BMI (B=0.181, p<0.01),
      obesity (B=1.061, p<0.000001) and hypercholesterolaemia (B=1.025, p<0.01). All of
      these relationships remained significant after adjustment for covariates, except
      for diabetes and sleep duration. Also, after adjustment, a significant
      relationship between insufficient sleep and hypertension emerged (B=1.039,
      p<0.001). When evaluated together, after adjustment for covariates, significant
      relationships remained between sleep duration <5h (versus 7h) and BMI (B=1.266,
      p<0.05), obesity (B=1.389, p<0.05), hypertension (B=1.555, p<0.01), heart attack
      (B=2.513, p<0.01) and stroke (B=1.807, p<0.05). It should be noted that
      relationships between sleep duration >9h (versus 7h) were seen for heart attack
      (B=1.863, p<0.001) and stroke (B=1.816, p<0.01). In these models, sleep
      insufficiency was associated with hypercholesterolaemia (B=1.031, p<0.01) and
      hypertension (B=1.027, p<0.05). CONCLUSIONS: These analyses show that both sleep
      duration and insufficiency are related to cardiometabolic health outcomes, and
      that when evaluated together, both variables demonstrate unique effects.

PMID- 23141933
TI  - National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI)
      symptom evaluation in multinational cohorts of patients with chronic
      prostatitis/chronic pelvic pain syndrome.
AB  - BACKGROUND: The assessment of patients with chronic prostatitis/chronic pelvic
      pain syndrome (CP/CPPS) in everyday practice and clinical studies relies on
      National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) scores
      for symptom appraisal, inclusion criteria for clinical trials, follow-up, and
      response evaluation. OBJECTIVE: We investigated multiple databases of CP/CPPS
      patients to determine the prevalence and impact of pain locations and types to
      improve our strategy of individualized phenotypically guided treatment. DESIGN,
      SETTING, AND PARTICIPANTS: Four major databases with CPSI scores for nonselected
      CP/CPPS clinic patients from Canada, Germany, Italy, and the United States.
      OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Individual question scores and
      subtotal and total scores of CPSI were described and correlated with each other.
      Ordinal regression analysis was performed to define pain severity categories.
      RESULTS AND LIMITATIONS: A total of 1563 CP/CPPS patients were included. Perineal
      pain/discomfort was the most prevalent pain symptom (63%) followed by testicular
      pain (58%), pain in the pubic area (42%) and penis (32%); reports of pain during
      ejaculation and voiding were 45% and 43%, respectively. European patients had a
      significantly higher number of pain localizations and symptoms compared with
      North American patients (p<0.001). Severity of pain correlated well with
      frequency of pain (r = 0.645). No specific pain localization/type was associated
      with more severe pain. Correlation of pain domain with quality of life (QoL) (r =
      0.678) was higher than the urinary domain (r = 0.320). Individually, pain
      severity (r = 0.627) and pain frequency (r = 0.594) correlated better with QoL
      than pain localization (r = 0.354). Pain severity categories results for NIH-CPSI
      item 4 (0-10 numerical rating scale for average pain) were mild, 0-3; moderate, 4
      6; severe, 7-10; CPSI pain domain (0-21): mild, 0-7; moderate, 8-13; and severe,
      14-21. CONCLUSIONS: Pain has more impact on QoL than urinary symptoms. Pain
      severity and frequency are more important than pain localization/type. Cut-off
      levels for disease severity categories have been identified that will prove
      valuable in symptom assessment and the development of therapeutic strategies.

PMID- 23141934
TI  - Nocturnal polyuria: it's all about definition, and be Patient!

PMID- 23141935
TI  - A historical landmark study comes to its end.

PMID- 23141936
TI  - Primary prevention and early detection of bladder cancer: two main goals for
      urologists.

PMID- 23141937
TI  - [Lymphoma diagnosis in general pathology practice: the hematopathologist point of
      view].

PMID- 23141939
TI  - [Pitfalls and update in haematopathology. Introduction and summary of the main
      take home messages].

PMID- 23141938
TI  - [Guidelines for adult diffuse gliomas WHO grade II, III and IV: pathology and
      biology. Societe franc aise de neuropathologie . Reseau de neuro-oncologie
      pathologique].
AB  - Pathological diagnosis plays a major role in the therapeutic management of adult
      diffuse gliomas. It is based on the histopathological analysis of a
      representative specimen. Therefore pathologists might be aware of the
      neuroradiological features of the lesions. Pathologists play a major role in the
      management of biological resources. Pathologists should classify adult gliomas
      according to WHO 2007 classification (histological subtype and grade). In
      addition, in order to provide the histomolecular classification of adult gliomas,
      search for molecular markers of diagnostic, prognostic or predictive of
      therapeutic responses must be performed by appropriate and validated
      immunohistochemical and molecular techniques. In all diffuse gliomas, whatever
      their grade, search for IDH1 R132H and P53 expression is required. Search for
      IDH1 minor mutations and IDH2 mutations is required in grade II and III IDH1
      R132H negative gliomas whereas 1p19q codeletion should be searched for in grade
      II and III gliomas with an oligodendroglial component. Search for EGFR
      amplification and MGMT promoter methylation is recommended. It is strongly
      recommended to fill the standardized form for pathology and molecular features
      (validated by the French Society of Neuropathology) in all adult diffuse gliomas.

PMID- 23141940
TI  - [Pitfalls and update in Haematopathology. Case 1. Follicular lymphoma grade 1-2
      according to the WHO classification 2008, "pseudo BCL2 negative" with low and
      heterogeneous expression of the CD10].

PMID- 23141941
TI  - [Pitfalls and update in haematopathology. Case 2. "Early phase" mantle cell
      lymphoma of the lymph node].

PMID- 23141942
TI  - [Pitfalls and update in haematopathology. Case 3. Mantle cell lymphoma,
      aggressive variant, pleomorphic].

PMID- 23141943
TI  - [Pitfalls and update in haematopathology. Case 4: limits of needle biopsies for
      assessment of lymphoid lesions].

PMID- 23141944
TI  - [ALK+ diffuse large B-cell lymphoma].

PMID- 23141945
TI  - [Pitfalls and update in haematopathology. Case 6. B-cell lymphoma,
      unclassifiable, with features intermediate between diffuse large B-cell lymphoma
      and Burkitt lymphoma].

PMID- 23141946
TI  - [Pitfalls and update in haematopathology. Case 7. Nodular lymphocyte predominant
      Hodgkin lymphoma].

PMID- 23141947
TI  - [Pitfalls and update in haematopathology. Case 8: angioimmunoblastic T-cell
      lymphoma].

PMID- 23141948
TI  - [Pitfalls and update in haematopathology. Conclusion].

PMID- 23141949
TI  - [Isolated splenic peliosis: a case report].
AB  - Peliosis is a rare vascular lesion that is usually found in the liver, and less
      frequently in other hematolymphoid organs. We report a case of isolated splenic
      peliosis discovered in a 65-year-old man with an erysipelas and a
      thrombocytopenia. The computed tomography abdominal scan revealed an heterogen
      multinodular splenic mass. Splenectomy was performed and platelet counts returned
      to normal levels. The histopathologic examination revealed dilations of sinuses
      in the red pulp. The endothelial cells lining cavities stain for CD8 and CD31 but
      not for CD34. Splenic peliosis is a rare benign disease of unknown aetiology,
      which belongs to the group of vascular neoplasms of the spleen. The final
      diagnosis is based on the pathology examen. We review the histologic and
      immunohistochemical arguments of this diagnostic and expose the differential
      diagnoses.

PMID- 23141950
TI  - [An unusual appendicular lesion].

PMID- 23141951
TI  - Ovulation-inducing factor in seminal plasma: a review.
AB  - Ovulation in mammals involves pulsatile release of GnRH from the hypothalamus
      into the hypophyseal portal system with subsequent release of LH from the
      anterior pituitary into systemic circulation. Elevated circulating concentrations
      of LH induce a cascade of events within the mature follicle, culminating in
      follicle rupture and evacuation. The broad classification of species as either
      spontaneous or induced ovulators is based on the type of stimulus responsible for
      eliciting GnRH release from the hypothalamus. In spontaneously ovulating species
      (e.g., human, sheep, cattle, horse, pigs), release of GnRH from the hypothalamus
      is triggered when, in the absence of progesterone, systemic estradiol
      concentrations exceed a threshold. In induced ovulators (e.g., rabbits, ferrets,
      cats, camelids), release of GnRH is contingent upon copulatory stimuli; hence,
      ovulation is not a regular cyclic event. Since a classic 1970 Peruvian study,
      dogma has maintained that physical stimulation of the genitalia during copulation
      is the primary trigger for inducing ovulation in alpacas and llamas. Exciting
      results of recent studies, however, provide direct evidence for the existence of
      an ovulation-inducing factor (OIF) in semen, and compel us to re-examine the
      mechanism of ovulation in both induced and spontaneous ovulators. Ovulation
      inducing factor in seminal plasma is a potent stimulant of LH secretion,
      ovulation and luteal gland development, and acts via a systemic rather than a
      local route. OIF is a protein molecule that is resistant to heat and enzymatic
      digestion with proteinase K. It has a molecular mass of 14kDa, and may be part of
      a larger protein complex or pro-hormone. The effect of OIF is dose-related and
      evident at physiologically relevant doses (i.e., as little as 1/100th that
      present in the ejaculate), and is mediated, in whole or in part, at the level of
      the hypothalamus in vivo. The factor exists in the seminal plasma of every
      species in which it has been examined thus far, including Bactrian camels,
      alpacas, llamas, cattle, horses, pigs, and koalas. Seminal plasma OIF does not
      appear to be a phylogenetic vestige in spontaneous ovulators since it (1) induced
      ovulation in pre-pubertal mice, (2) altered ovarian follicular wave dynamics in
      cows, and (3) elicited LH release in vitro from primary pituitary cell cultures
      of rats, mice, guinea pigs, rabbits, llamas and cows.

PMID- 23141952
TI  - Special issue. Preface.

PMID- 23141953
TI  - Reproductive performance and backflow study in cervical and post-cervical
      artificial insemination in sows.
AB  - The present study was developed to evaluate multiparous sow reproductive
      performance and backflow in post-cervical artificial insemination (post-CAI)
      using a reduced number of sperm than in cervical artificial insemination (CAI).
      The experimental groups were divided into sows inseminated by: 1) cervical
      artificial insemination (CAI): 3*10(9) spermatozoa/80 ml; 2) post-CAI: 1.5*10(9)
      spermatozoa/40 ml (post-CAI 1); 3) post-CAI using 1*10(9) spermatozoa/26 ml (post
      CAI 2). Post-CAI 1 reproductive parameters were similar to those of post-CAI 2
      (except for live born litter size which was greater in post-CAI 1) and better
      than for the CAI group (p<0.01). In a second experiment the backflow volume,
      number of sperm, and sperm quality in the backflow were studied in the 3
      experimental groups. The % of volume and spermatozoa in the backflow was higher
      in the CAI group (p<0.05) than post-CAI groups (statistically similar between
      them). Moreover, the quality parameters (motility, progressive motility,
      viability, chromatin decondensation and morphology) in backflow semen were
      identical in all three experimental groups, but differed as regards the original
      insemination dose incubated inside a colostomy bag (sperm quality control group).
      The present study shows that the use of post-CAI (either post-CAI 1 or 2) in
      field conditions can be recommended because the efficiency is similar (in the
      case of post-CAI 2) or higher (post-CAI 1) than when using the traditional method
      (CAI), representing a reduction cost.

PMID- 23141954
TI  - Numerical estimation of 3D mechanical forces exerted by cells on non-linear
      materials.
AB  - The exchange of physical forces in both cell-cell and cell-matrix interactions
      play a significant role in a variety of physiological and pathological processes,
      such as cell migration, cancer metastasis, inflammation and wound healing.
      Therefore, great interest exists in accurately quantifying the forces that cells
      exert on their substrate during migration. Traction Force Microscopy (TFM) is the
      most widely used method for measuring cell traction forces. Several mathematical
      techniques have been developed to estimate forces from TFM experiments. However,
      certain simplifications are commonly assumed, such as linear elasticity of the
      materials and/or free geometries, which in some cases may lead to inaccurate
      results. Here, cellular forces are numerically estimated by solving a
      minimization problem that combines multiple non-linear FEM solutions. Our
      simulations, free from constraints on the geometrical and the mechanical
      conditions, show that forces are predicted with higher accuracy than when using
      the standard approaches.

PMID- 23141955
TI  - A novel three-dimensional shoulder rhythm definition that includes overhead and
      axially rotated humeral postures.
AB  - Although the orientations of the scapula and clavicle in space are difficult to
      measure experimentally, the existence of a mathematically quantifiable shoulder
      rhythm allows their estimation based on thoracohumeral orientation. This study
      quantified the shoulder rhythm for arm postures that represent the right-handed
      reachable volume. Fourteen male and fourteen female participants performed static
      arm postures spread over five arm elevation angles: 0 degrees , 45 degrees , 90
      degrees , 135 degrees  and 180 degrees , three elevation planes: 0 degrees , 45
      degrees  and 90 degrees  and, three axial rotations: maximum internal, neutral,
      and maximum external rotation. Kinematic data was collected using a passive
      motion-tracking system. Bone rotations were calculated using Euler angles and
      continuous parsimonious prediction models were generated to describe the rhythm
      for each angle. Linear models were obtained for all scapular angles and for all
      clavicular angles except elevation, for which a quadratic model was derived.
      Axial rotation of the humerus did not influence scapular retraction/protraction
      and plane of elevation did not influence clavicular elevation (p>.05). Elevation
      angle was the largest contributor to lateral rotation and posterior tilt of the
      scapula and all clavicular angles, while plane of elevation was the largest
      contributor to scapular protraction. The shoulder rhythm models can be
      incorporated into existing and future shoulder biomechanical models to determine
      relative shoulder bony orientations and subsequently determine muscular
      capacities. The novelty of the described models is their deliberate consideration
      of axial humeral rotation and the inclusion of multiple overhead postures, the
      combination of which generates a rhythm based on an unprecedentedly comprehensive
      range of humeral postures.

PMID- 23141956
TI  - A method to determine the orientation of the upper arm about its longitudinal
      axis during dynamic motions.
AB  - Inaccuracy in determining the orientation of the upper arm about its longitudinal
      axis (twist orientation) has been a pervasive problem in sport biomechanics
      research. The purpose of this study was to develop a method to improve the
      calculation of the upper arm twist orientation in dynamic sports activities. The
      twist orientation of the upper arm is defined by the orientation of its
      mediolateral axis. The basis for the new method is that at any angle in the
      flexion/extension range of an individual's elbow, it is possible to define a true
      mediolateral axis and also a surrogate mediolateral axis perpendicular to the
      plane containing the shoulder, elbow and wrist joints. The difference between the
      twist orientations indicated by these two versions of the mediolateral axis will
      vary from one elbow angle to another, but if the elbow joint deforms equally in
      different activities, for any given subject the difference should be constant at
      any given value of the elbow angle. Application of the new method required
      individuals to execute sedate elbow extension trials prior to the dynamic trials.
      Three-dimensional motion analysis of the sedate extension trials allowed
      quantification of the difference between the true and surrogate mediolateral axes
      for all angles in the entire flexion/extension range of an individual's elbow.
      This made it possible to calculate in any dynamic trial the twist orientation
      defined by the true mediolateral axis from the twist orientation defined by the
      surrogate mediolateral axis. The method was tested on a wooden model of the arm.

PMID- 23141957
TI  - Lifting up and laying down a weight causes high spinal loads.
AB  - Lifting up weights from a cupboard or table and putting them back are activities
      of daily living. Patients with spinal problems want to know whether they should
      avoid these activities. However, little is known about the spinal forces during
      these activities and about the effect of level height. Loads on a telemeterized
      vertebral body replacement were measured in 5 patients. The effect of level
      height when lifting or setting down weights of 0.01, 1.5 and 3.0 kg in a standing
      posture were investigated. Furthermore, these weights were lifted and set down
      with a stretched arm while sitting at a table. No instructions were given on how
      to perform the task. For these activities, forces as high as 5 times the value
      for standing alone were measured. In 2 patients, implant loads decreased with
      increasing level height. In the other patients the effect of level height was
      small. Lifting a weight from a table with a stretched arm while sitting led to a
      strong increase of the maximum implant force. Setting down the weight usually
      caused a slightly higher maximum implant force than lifting it. Forces on a
      vertebral body replacement during lifting and setting down a weight varied
      strongly when no precise instructions were given on how to perform the activity.
      Thus, the measured forces are representative for such activities performed in
      daily life. This, however, led to wide variations in measured data. Compared to
      the value for standing, 5 times higher forces were measured for lifting and
      setting down of weights. This suggests that these activities should be avoided by
      patients who have spinal problems.

PMID- 23141958
TI  - Pertussis outbreaks and pertussis vaccines: new insights, new concerns, new
      recommendations?

PMID- 23141959
TI  - The anthropometric match between high school learners of the Cape Metropole area,
      Western Cape, South Africa and their computer workstation at school.
AB  - STUDY DESIGN: Descriptive study. OBJECTIVE: The objective of this study was to
      present anthropometric data from high school students in Cape Metropole area,
      Western Cape, South Africa that are relevant for chair design and whether the
      dimensions of computer laboratory chairs currently used in high schools match
      linear anthropometrics of high-school students. Summary of Background Data.
      Learner-chair mismatch is proposed as a cause of poor postural alignment and
      spinal pain in adolescents. A learner-chair mismatch is defined as the
      incompatibility between the dimensions of a chair and the anthropometric
      dimensions of the learner. Currently, there is no published research to ascertain
      whether the furniture dimensions in school computer laboratories match the
      anthropometrics of the students. This may contribute to the high prevalence of
      adolescent spinal pain. METHODS: The sample consisted of 689 learners, 13-18
      years old. The following body dimensions were measured: stature, popliteal
      height, buttock-to-popliteal length and hip width. These measurements were
      matched with the corresponding chair seat dimensions: height, depth and width.
      Popliteal and seat height mismatch was defined when the seat height is either
      >95% or <88% of the popliteal height. Buttock-popliteal length and seat depth
      mismatch was defined when the seat depth is either >95% or <80% of the buttock
      popliteal length. Seat width mismatch is defined where the seat width should be
      at least 10% and at the most 30% larger than hip width. RESULTS: An 89% of
      learners did not match the seat. Five percent of learners matched the chair
      depth, the majority was found to be too big. In contrast, 65% of the learners
      matched the chair width dimension. CONCLUSIONS: A substantial mismatch was found.
      The school chairs failed standard ergonomics recommendations for the design of
      furniture to fit the user. This study supports the conclusion that there is no
      one-size-fits-all solution. There is an urgent need for chairs that are of
      different sizes or that are adjustable.

PMID- 23141960
TI  - Circadian rhythms and the effect of glucocorticoids on expression of the clock
      gene period1 in canine peripheral blood mononuclear cells.
AB  - Circadian rhythms have a periodicity of approximately 24h and, in mammals, are
      regulated by clock genes. In this study, expression profiles of clock genes
      (per1, per2, clock, bmal1 and cry1) were investigated over a single 24h period by
      real-time PCR in peripheral blood mononuclear cells (PBMCs) of healthy dogs and
      canine PBMCs treated in vitro and in vivo with glucocorticoids. Only per1 mRNA
      exhibited daily rhythms in canine PBMCs. Canine PBMCs cultured with dexamethasone
      in vitro had dose- and time-dependent increases in per1 mRNA expression.
      Intravenous injection of dexamethasone increased expression of per1 in canine
      PBMCs in vivo. Rhythmic expression of per1 in PBMCs could be used as a molecular
      marker for monitoring circadian rhythms and the effects of drugs on clock genes
      in dogs.

PMID- 23141961
TI  - A behaviour-based pain scale for horses with acute colic: scale construction.
AB  - A validated tool for assessing the severity of acute abdominal pain is needed for
      the effective management of colic in horses. Two behaviour-based colic pain
      scales were constructed by combining together mathematical and judgemental
      approaches. The mathematical approach identified easily-recognised pain
      behaviours to select as items. The judgemental approach further modified the
      items and weighted them based on expert-opinion. Thirty equine practitioners
      assessed the level of pain demonstrated in 23 film clips of clinical cases
      exhibiting signs of acute abdominal pain prospectively using a 10cm visual
      analogue scale (VAS). The practitioners also identified behaviours noted in each
      clip from a checklist of 23 behaviours identified from the literature. Nine
      behaviours had insignificant bias and moderate-to-excellent inter-observer
      agreement (multirater kappas: 0.5-0.95). Six experienced veterinarians then
      completed questionnaires in an iterative Delphi process to independently judge 15
      items that best reflected severity of pain out of 42 items generated from the
      literature. Two behaviours were generated by the process. Subsequently, an
      advisory panel of three equine practitioners constructed two clinimetric-type
      scales based on the results of both approaches. The two resulting equine acute
      abdominal pain scales (EAAPS) included 12 behaviours. One weight was assigned to
      each behaviour in the EAAPS-1. In the EAAPS-2, gradations of weights were
      assigned, based on the frequency of the behaviour being demonstrated. The EAAPS
      scales are the first pain severity scales designed specifically for clinical use
      in cases of acute colic utilising the clinimetric approach to scale construction.
      Further studies are underway to validate the scales.

PMID- 23141962
TI  - Dietary restriction in combination with a nutraceutical supplement for the
      management of equine metabolic syndrome in horses.
AB  - Few studies have examined the effect of dietary restriction in horses with equine
      metabolic syndrome (EMS). This study aimed to determine improvements in insulin
      sensitivity following dietary restriction for 6 weeks, and to determine if the
      improvement would be greater in horses receiving short-chain fructo
      oligosaccharides (sc-FOS). Dietary management involved feeding grass hay,
      restricted to 1.25% of body mass (BM) as daily dry matter intake and soaked in
      cold water prior to feeding, with the addition of a vitamin and mineral
      nutraceutical supplement with or without the addition of sc-FOS (10 g/100 kg).
      Soaking the hay resulted in a significant reduction in non-structural
      carbohydrates (38%, P = 0.01), digestible energy (6.78%, P = 0.01) and water
      soluble minerals. Following 6 weeks of dietary restriction with soaked grass hay
      and nutraceutical supplement, horses lost an average of 6.8% BM and showed
      reductions in body condition score (BCS) and belly circumference. Sensitivity to
      insulin improved overall, as determined by the total insulin response during the
      combined glucose insulin test. The magnitude of improvement in insulin
      sensitivity was associated with the degree of insulin resistance recorded at
      outset, and the extent of overall losses in BM and BCS, but was independent of
      the addition of sc-FOS. The nutraceutical supplement was highly palatable and no
      adverse effects were noted. From the findings of this study a strict dietary
      program in combination with a specifically designed vitamin and mineral
      nutraceutical supplement can be recommended to obtain rapid improvements in BM,
      BCS and insulin sensitivity of animals presenting with EMS.

PMID- 23141963
TI  - Circadian pattern of acute phase proteins in the saliva of growing pigs.
AB  - The circadian rhythm of the acute phase proteins (APPs) haptoglobin (Hp) and C
      reactive protein (CRP) was assessed in saliva samples from 18- and 21-week old
      pigs. Saliva was collected at 07.00, 11.00, 15.00 and 19.00 h on two consecutive
      days and the Hp and CRP concentrations were quantified using two species
      specific, time-resolved immunofluorometric assays. Salivary Hp levels were
      significantly higher (P < 0.001) in the morning compared to late afternoon (0.68
      and 0.37 MUg/mL, respectively) although the magnitude of the difference was much
      lower than is produced by inflammatory conditions. No significant differences
      were observed in CRP concentrations. Although the concentration of both APPs was
      higher in the 21- compared to the 18-week old pigs (P < 0.0001), no differences
      were observed in the circadian rhythm of these APPs when the two age groups were
      compared. Animal gender did not influence the circadian pattern of either APP,
      although the mean salivary CRP levels were higher in females (P < 0.05).

PMID- 23141964
TI  - Matrix metalloproteinases and vascular endothelial growth factor expression in
      canine leukaemias.
AB  - Matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF)
      play a coordinated role during neoplastic invasion and proliferation. VEGF and
      MMPs expression was investigated in canine leukaemias by immunocytochemistry (MMP
      9, MMP-2, VEGF-A) and quantitative RT-PCR (MMP-2, MMP-9, MT1-MMP, TIMP-1, TIMP-2,
      RECK, VEGF-A, VEGF-164). Blood samples were obtained from dogs with acute
      leukaemia (AL; n = 11) and chronic lymphocytic leukaemia (CLL; n = 12). Levels of
      MMP-9, TIMP-1 and VEGF-A were higher in CLL than AL and controls. Expression of
      TIMP-2 and MT1-MMP mRNA was significantly higher in AL than CLL. Significant
      positive correlations were found between MMP-9 and TIMP-1 and between MMP-9 and
      VEGF-A in CLL. These results suggest a potential role of MMP-9, MT1-MMP, TIMP-1,
      TIMP-2 and VEGF in tissue migration and angiogenesis in canine leukaemia.

PMID- 23141965
TI  - Computational grading of hepatocellular carcinoma using multifractal feature
      description.
AB  - Cancer grading has become an important topic in the field of image interpretation
      based computer aided diagnosis systems. This paper proposes a novel feature
      descriptor to observe the characteristics of histopathological textures in a
      discriminative manner. The proposed feature descriptor utilizes fractal geometric
      analysis with four multifractal measures to construct an eight dimensional
      feature space. The proposed method employed a bag-of-feature-based classification
      model to discriminate a set of hepatocellular carcinoma images into five
      categories according to Edmondson and Steiner's grading system. Three feature
      selection methods were utilized to obtain the most discriminative features of
      codeword dictionary (codebook). Furthermore, we incorporated four other textural
      feature descriptors: Gabor-filters, LM-filters, local binary patterns, and
      Haralick, to obtain a benchmark of the accuracy of the classification. Two
      experiments were performed: (i) classifying non-neoplastic tissues and tumors and
      (ii) grading the hepatocellular carcinoma images into five classes. Experimental
      results indicated the significance of the multifractal features for describing
      the histopathological image texture because it outperformed other four feature
      descriptors. We graded a given ROI image by defining a threshold-based majority
      voting rule and obtained an average correct classification rate around 95% for
      five classes classification.

PMID- 23141966
TI  - Prevalence of the Leptospira serovars bratislava, grippotyphosa, mozdok and
      pomona in French dogs.
AB  - Although most French dogs are correctly vaccinated against leptospirosis with
      inactivated strains of canicola and icterohaemorrhagiae, the disease is still
      very prevalent in France raising the question of whether the vaccines used
      require updating. The aim of the present study was to provide serological data
      regarding circulation of the Leptospira serovars: grippotyphosa, bratislava,
      pomona and mozdok, which are contained in vaccines available in other parts of
      the world and which could be rapidly adapted for France. Results indicated that
      the epidemiology was consistent with the circulation of Leptospira belonging to
      the serogroups Australis and Grippotyphosa and that the case to support the
      inclusion of either pomona or mozdok in a dog vaccine for France was weak.

PMID- 23141967
TI  - [Bariatric surgery in children: how can we combat the prejudice?].

PMID- 23141968
TI  - Resveratrol affects undifferentiated and differentiated PC12 cells differently,
      particularly with respect to possible differences in mitochondrial and autophagic
      functions.
AB  - Since resveratrol is considered to exert a unique dual effect, protective for
      normal cells but toxic to tumor cells, its action on undifferentiated (original)
      and differentiated PC12 cells was analyzed, because undifferentiated cells are
      tumorigenic and differentiated ones are neuronal in nature. Compared to
      resveratrol-untreated cells in both undifferentiated and differentiated cell
      groups, cells treated with different doses of resveratrol, at dosages of 1, 10
      and 100 MUM, showed the following alterations. Dying/dead cells were
      significantly increased in a dose-dependent manner in undifferentiated cells, but
      they were unchanged at doses of up to 10 MUM resveratrol in differentiated cells.
      In living cells, neurites were short in undifferentiated cells, but drastically
      elongated with an increased number in differentiated cells. The expression of
      SIRT1 was drastically reduced in undifferentiated cells, but stable in
      differentiated cells. SIRT3 was significantly enhanced in a dose-dependent manner
      at resveratrol doses of up to 10 MUM in both cells, with reduction and more
      enhanced at a dosage of 100 MUM in undifferentiated and differentiated cells,
      respectively. Mitochondrial number and ATP synthase beta subunit expression was
      unaltered at doses of up to 10 MUM and were significantly reduced at doses of 100
      MUM in undifferentiated cells, but they were significantly increased in a dose
      dependent manner, with a slight reduction in the ATP synthase at doses of 100
      MUM, in differentiated cells. In a dose-dependent manner, the number of
      autophagosomes and the LC3-II/LC3-I ratio were significantly less in
      undifferentiated cells and greater in differentiated cells. Also, in a dose
      dependent manner, the expression of phosphorylated AMP-activated kinase (AMPK)
      was significantly less in undifferentiated cells and greater in differentiated
      cells. Resveratrol-induced AMPK suppression and activation, possibly through the
      modulation of SIRT protein activity, may thus be related to the inhibition and
      promotion of mitochondrial and autophagic functions, leading to cell death and
      survival in undifferentiated and differentiated cells, respectively.

PMID- 23141969
TI  - The largest reported epineural ganglion of the ulnar nerve causing cubital tunnel
      syndrome: case report and review of the literature.
AB  - We describe the largest reported epineural ganglion of the ulnar nerve arising in
      the cubital tunnel. A 54-year-old male, driver presented with progressive
      symptoms of left sided cubital tunnel syndrome. Surgery demonstrated a 11 * 3 cm
      ganglion which was successfully removed. Post-operatively the patient
      demonstrated partial recovery with no recurrence of the ganglion.

PMID- 23141970
TI  - Mimotopes selected by biopanning with high-titer HIV-neutralizing antibodies in
      plasma from Chinese slow progressors.
AB  - OBJECTIVE: One approach to identifying HIV-1 vaccine candidates is to dissect the
      natural antiviral immune response in treatment-naive individuals infected for
      over ten years, considered slow progressor patients (SPs). It is suspected that
      SP plasma has strongly neutralizing antibodies (NAb) targeting specific HIV viral
      epitopes. METHODS: NAbs levels of 11 HIV-1-infected SPs were detected by PBMC
      based neutralization assays. To investigate SP NAb epitope, this study used a
      biopanning approach to obtain mimotopes of HIV-1 that were recognized by SP
      plasma NAbs. IgG was purified from high-titer NAb SP plasma, and used as the
      ligand for three rounds of biopanning to select HIV-specific mimotopes from a
      phage-displayed random peptide library. Double-antibody sandwich ELISA,
      competitive inhibition assays, and peptide sequence analysis were used to
      evaluate the characteristics of phage-borne mimotopes. RESULTS: SPs had
      significantly more plasma neutralizing activity than typical progressors (TPs)
      (p=0.04). P2 and P9 plasma, which have highest-titer HIV-NAb, were selected as
      ligands for biopanning. After three rounds of biopanning, 48 phage clones were
      obtained, of which 22 clones were consistent with requirement, binding with HIV-1
      positive plasma and unbinding with HIV-1 negative plasma. Compared with linear
      HIV-1 protein sequence and HIV-1 protein structure files, only 12 clones were
      possible linear mimotopes of NAbs. In addition, the C40 clone located in gp41 CHR
      was found to be a neutralizing epitope, which could inhibit pooled HIV-1 positive
      plasma reaction. CONCLUSION: Biopanning of serum IgG can yield mimotopes of HIV-1
      related antigen epitopes. This methodology provides a basis for exploration into
      HIV-1-related antigen-antibody interactions and furthers NAb immunotherapy and
      vaccine design.

PMID- 23141971
TI  - Purple urine bag syndrome in an elderly subject.

PMID- 23141972
TI  - Lyme disease in the state of Tocantins, Brazil: report of the first cases.
AB  - Lyme disease is an underdiagnosed zoonosis in Brazil. There are no cases
      registered in the state of Tocantins, the newest Brazilian state. The cases of
      three patients in contact with rural areas in three Tocantins' districts are
      herein described, and the Brazilian literature is reviewed.

PMID- 23141973
TI  - Recurrent pulmonary mucormycosis after lobectomy in a non-smoking patient without
      predisposing risk factors.
AB  - Pulmonary mucormycosis is a very rare clinical condition in patients without
      underlying risk factors. A limited number of cases have been reported in
      predominantly elderly patients; history of smoking appears to be a common
      feature. A case of non-smoking male who developed pulmonary mucormycosis with the
      longest reported follow-up is presented. In addition, this is also the first
      reported case with disease recurrence after lobectomy (two years) in an
      immunocompetent host. Treatment with an additional lobectomy and amphotericin B
      was successful in this patient.

PMID- 23141974
TI  - Japanese encephalitis: a review of the Indian perspective.
AB  - Japanese encephalitis virus (JEV) causes Japanese encephalitis, which is a
      leading form of viral encephalitis in Asia, with around 50,000 cases and 10,000
      deaths per year in children below 15 years of age. The JEV has shown a tendency
      to extend to other geographic regions. Case fatality averages 30% and a high
      percentage of the survivors are left with permanent neuropsychiatric sequelae.
      Currently, there is no cure for JEV, and treatment is mainly supportive. Patients
      are not infectious, but should avoid further mosquito bites. A number of
      antiviral agents have been investigated; however, none of these have convincingly
      been shown to improve the outcome of JEV. In this review, the current knowledge
      of the epidemiology and the pathogenesis of this deadly disease have been
      summarized.

PMID- 23141975
TI  - Incidence and outcome of ventilator-associated pneumonia (our experience).

PMID- 23141976
TI  - The calculus of giving back.

PMID- 23141977
TI  - Surgical location of open tracheostomies: in the operating room or at the
      bedside?

PMID- 23141979
TI  - How should the articular disc position be analyzed?

PMID- 23141981
TI  - Of course, early recognition of relapses in squamous cell carcinoma of the tongue
      is mandatory!

PMID- 23141983
TI  - Magnetic resonance imaging evaluation of temporomandibular joint and associated
      soft tissue changes following acute condylar injury.
AB  - PURPOSE: This study evaluated the role of magnetic resonance imaging (MRI) in
      cases of acute condylar injury and assessed soft tissue damage such as disc
      displacement, capsular tear, and hemarthrosis within the temporomandibular joint
      (TMJ). PATIENTS AND METHODS: This prospective study was conducted in 15 patients
      who presented with unilateral or bilateral condylar fracture or contusion with a
      unilateral or bilateral diagnosis of TMJ sprain/strain. Patients with trauma of
      less than 7 days previously with a unilateral or bilateral condylar fracture or
      contusion with a diagnosis of TMJ sprain/strain were included in the present
      study. The clinical diagnosis of TMJ sprain was made and further classified and
      graded according to the severity and type of injury. On confirmation of the
      diagnosis of condylar injury, patients underwent evaluation by MRI. All patients
      were treated by closed reduction of the condylar fracture and intermaxillary
      fixation for 14 to 21 days. RESULTS: Of the 15 patients, 5 were children and 10
      were adults. Of all 17 TMJ cases (2 bilateral, 13 unilateral), 2 condylar
      fractures were of the high variety and 13 were of the low variety. MRI diagnosis
      of disc displacement was established in 8 of 17 TMJ cases. There was a
      significant association between degrees of condylar injury and the MRI diagnosis
      of displaced disc and hemarthrosis. However, an MRI finding of capsular tear was
      not significantly associated with the degree of condylar injury. CONCLUSIONS:
      Soft tissue changes of the TMJ can be predicted accurately by MRI and are in
      direct proportion to the severity of the condylar injury of the mandible. Among
      the soft tissue changes, disc displacement and hemarthrosis seem to affect the
      outcome of functional treatment.

PMID- 23141984
TI  - Is entire removal of a post-traumatic temporomandibular joint ankylotic site
      necessary for an optimal outcome?
AB  - PURPOSE: Temporomandibular joint (TMJ) ankylosis that occurs after TMJ condylar
      fracture constitutes a treatment challenge. The purpose of the present study is
      shed light on an alternative treatment approach for certain such cases where the
      displaced condylar head or part of it can be detected in computed tomography. The
      leading principle of this protocol is accurate removal of the ankylotic mass
      only, leaving the condyle-disc apparatus un-touched. PATIENTS AND METHODS: The
      study is based on such cases of post trauma ankylosis where the displace condyle
      was detected. Thirteen cases are reported (10 unilateral and 3 bilateral) age
      ranged from 8 to 51 years (mean 20). All patients were treated according to the
      presented protocol that emphasizes the significance of preserving the condyle
      disc apparatus while accurately removing the ankylotic mass. To achieve the
      required precision, 3-dimensional computed tomography was used. An integral part
      of the treatment plan is intensive guided physiotherapy, which is intended to re
      establish normal joint function, the original occlusion and facial symmetry (in
      growing individuals). RESULTS: The patients were followed up for 6 to more than
      60 months. After guided physiotherapy, all patients had significant postoperative
      improvement in maximal mouth opening from a mean of 18.4 mm (range 8 to 28) to a
      mean of 41.2 mm (range 35 to 50). All patients had returned to their original
      occlusion. In all the growing patients, a marked improvement in facial symmetry
      was observed. CONCLUSIONS: In post trauma ankylosis the displaced head of the
      condyle and disc should be searched for using computed tomography. If detected we
      recommend its preservation while accurately remove only the ankylotic mass. Using
      this approach, in addition to achieving adequate mandibular motion, good
      occlusion, and normal facial growth, major surgery, with all its inconveniences
      and potential complications, is avoided.

PMID- 23141985
TI  - Fast separation of triterpenoids by supercritical fluid
      chromatography/evaporative light scattering detector.
AB  - The screening of plant material, the chemical composition, the abundance and the
      biological activity of triterpenoids are of a major economical importance. The
      classical analytical methods, such as TLC, GC, and HPLC are either little
      resolutive, or require derivatization steps, or fail in sensitivity. The
      supercritical fluid chromatography/evaporative light scattering detector
      (SFC/ELSD) coupling provides high resolution, fast analysis and higher responses
      for the analysis of triterpenoids. After the initial screening of seven
      stationary phases to select the well suited one, analytical conditions (modifier
      percentage, from 10 to 3%; backpressure (from 12 to 18 MPa) and temperature (from
      15 to 25  degrees C) were studied to improve the separation, and ELSD detection
      of a standard mixture composed of 8 triterpenoids (oleanolic acid, erythrodiol,
      beta-amyrin, ursolic acid, uvaol, betulinic acid, betulin, lupeol). Applied to
      apple pomace extracts, this method allows the separation of about 15 triterpenoid
      compounds, in less than 20 min, with isocratic conditions. Moreover, the ELSD
      response is dramatically higher than the one provided by UV detection, and avoids
      derivatization steps. An attempt to identify some compounds was done by
      collecting chromatographic peaks and further analyzing them with mass
      spectrometry. Complete identification or molecular formula could be proposed for
      11 compounds. However, due to the presence of position and orientation isomers
      the absolute identification remains difficult, despite some retention rules
      deduced from the standard analysis.

PMID- 23141986
TI  - Recent developments on polysaccharide-based chiral stationary phases for liquid
      phase separation of enantiomers.
AB  - This paper summarizes recent developments in the synthesis, application and
      mechanistic studies on polysaccharide-based chiral stationary phases (CSPs) for
      liquid phase separation techniques. Together with applications in conventional
      high-performance liquid chromatography (HPLC) applications in nano-liquid
      chromatography (nano-LC), capillary electrochromatography (CEC), super/sub
      critical fluid chromatography (SFC) and preparative and product scale separations
      are also summarized. In the final part of the overview mechanistic aspects and
      some unusual effects observed in HPLC with these materials are shortly discussed
      and the author's view regarding future trends in this field is provided.

PMID- 23141987
TI  - Severe metabolic acidosis and Fanconi syndrome during stavudine and abacavir
      therapy in a resource-limited setting.

PMID- 23141988
TI  - Determination of urine tumor necrosis factor, IL-6, IL-8, and serum IL-6 in
      patients with hemorrhagic fever with renal syndrome.
AB  - OBJECTIVE: The aim of this study was to explore the role of cytokines in the
      pathogenesis of hemorrhagic fever with renal syndrome (HFRS). METHODS: Double
      antibody sandwich ELISA was used to determine serum interleukin (IL)-6, urine
      tumor necrosis factor (TNF), IL-6, and IL-8 levels in 56 patients with HFRS.
      RESULTS: Serum IL-6, urine TNF, IL-6, and IL-8 concentrations in HFRS patients
      were significantly higher than those in the control group (p<0.001). The
      concentrations increased at fever stage, then continued to increase during the
      hypotension stage and peaked at the oliguria stage. The concentrations of serum
      IL-6, urine TNF, IL-6, and IL-8 increased according to the severity of the
      disease, and differed greatly among different types of the disease. Serum IL-6
      had remarkable relationships with serum specific antibodies. It was positively
      related to serum beta2-microglobulin (beta2-MG), blood urea nitrogen (BUN), and
      creatinine (Cr). Significant positive relationships were also found both between
      urine IL-6 and TNF, and between IL-6 and IL-8 (r=0.5768, p<0.05; r=0.3760,
      p<0.01). CONCLUSION: TNF, IL-6, and IL-8 were activated during the course of the
      disease. IL-6 was associated with the immunopathological lesions caused by the
      hyperfunction of the humoral immune response. IL-6, IL-8 and TNF were involved in
      renal immune impairment. Determining them might, to a certain extent, be useful
      in predicting the prognosis and outcome of patients with HFRS.

PMID- 23141989
TI  - Linezolid-induced angioedema and urticaria in a patient with renal failure.

PMID- 23141990
TI  - Increased serum levels of soluble tumor necrosis factor receptor-2 (sTNFR2) in
      patients with active toxoplasmic retinochoroiditis.
AB  - This study aimed to investigate the serum levels of the cytokine TNF-alpha and
      its soluble receptors (sTNFR1 and sTNFR2) in patients with toxoplasmosis
      retinochoroiditis (TR) and controls. 37 patients with TR and 30 subjects with
      positive serology for toxoplasmosis but without history and signs of uveitis were
      included in this study. Serum concentrations of TNF-alpha, sTNFR1, and sTNFR2
      were determined by ELISA. Serum concentrations of TNF-alpha and sTNFR1 were
      similar in controls (mean +/- SD median values; 56.57+/-141.96 and 504.37+/
      163.87, respectively) and TR patients (mean +/- SD values, 121.62+/-217.56 and
      511.15+/-189.30, respectively). Serum concentrations of sTNFR2 were higher in the
      uveitis group when compared to the control group (respectively, mean +/- SD
      values, 1734.84+/-379.32 and 1442.75+/-309.47; p=0.002). There was no association
      between the serum levels of the molecules and the time of first symptoms,
      severity of vitreous haze, size or localization of active lesions, levels of
      visual acuity, and presence of vasculitis. These results suggest that TR is
      associated with changes in the circulating levels of inflammatory biomarkers, but
      they are not correlated with local/ocular signs.

PMID- 23141991
TI  - Odontogenic infections in the Internal Medicine Service.

PMID- 23141992
TI  - Tuberculous otomastoiditis complicated by sinus vein thrombosis.

PMID- 23141993
TI  - Analytical validation of anti-toxoplasma IgG immunoassays.
AB  - There are often discrepancies when using different methods to measure anti
      Toxoplasma gondii IgG levels in patient samples. The diagnostic performance of a
      chemiluminescent immunoassay (CLIA) and an enzyme-linked fluorescent assay (ELFA)
      used as confirmatory tests for samples identified as positive or equivocal by an
      electrochemiluminescent immunoassay (ECLIA) were examined. Cut-off values were
      those stated by the manufacturer, and Western blot was used to confirm the
      results of all methods. All samples identified as positive by ECLIA (n=93) were
      confirmed as positive by Western blot, as were 14 of the 28 samples identified as
      equivocal. When these 121 samples were retested, the sensitivities of CLIA and
      ELFA were 64.4% and 73.8%, respectively. Both methods exhibited a specificity of
      100%. This study confirms that the results obtained from the different
      immunoassays are not comparable, and neither CLIA nor ELFA should be used to
      confirm ECLIA results, which should instead be confirmed by methods such as
      Western blot or Sabin-Feldman dye test.

PMID- 23141994
TI  - Vertebral osteomyelitis and epidural abscesses caused by Prevotella oralis: a
      case report.
AB  - An interesting case of pyogenic vertebral osteomyelitis with multiple epidural
      abscesses caused by non-pigmented Prevotella oralis is reported. The patient was
      a 68-year-old female who presented to the emergency room (ER) with severe pain
      and tenderness in her lower back with fever. She had recently undergone
      esophagogastroduodensoscopy (EGD) for complaints of esophageal reflux, which
      showed submucosal cyst in the esophagus. Magnetic resonance imaging (MRI) of the
      thoracic spine revealed multiple spinal epidural abscesses with signal
      enhancement at the level of T6 and T7, suggestive of vertebral osteomyelitis. Two
      blood cultures drawn one hour apart grew Prevotella oralis. The body fluid
      aspirated from the abscesses was also positive for the anaerobic commensal P.
      oralis. Necrosis associated with the submucosal cyst was implicated as the cause
      of sepsis and osteomyelitis due to this organism.

PMID- 23141995
TI  - Effects of platelet rich fibrin alone used with rigid titanium barrier.
AB  - OBJECTIVE: Platelet-rich fibrin (PRF) is a platelet and leukocyte rich and
      platelet preparation that concentrates various growth factors and therefore has
      the potential to be used as regenerative treatment. The aim of study was to
      assess the effects of platelet rich fibrin (PRF) on bone augmentation when used
      in conjunction with titanium barrier a rabbit calvaria model. STUDY DESIGN:
      Twenty-four adult male New Zealand rabbits were used in this study. Two titanium
      barriers were fixed on each rabbit's calvarium. The rabbits were divided into
      four groups (group one is control and the other three groups are experimental)
      and each group contains 6 animals. PRF, anorganic bovine bone (ABB), and biphasic
      calcium phosphate (BCP) were used with titanium barriers in the experimental
      groups. Any materials were not used in the control group. Half of the animals
      were sacrificed after 1 month, and the rest were sacrificed after 3 months.
      Histomorphometric evaluation was carried out in order to compare new bone
      formation among the groups. RESULTS: Significantly more new bone area was noted
      in the PRF alone group than in the control group, no statistically significant
      differences were found among PRF, BCP and ABB groups after 1 month. PRF and ABB
      also had superior effects in new bone formation area control to the BCP group
      after 3 months. CONCLUSION: PRF may offer the ease of use, simple handling, and
      enhanced delivery of growth factors during the bone augmentation procedures. When
      used in conjunction with the titanium barriers, PRF use can increase the quality
      of the newly formed bone and enhance the rate of bone formation due to the
      concentration of growth factors.

PMID- 23141996
TI  - Silymarin for diabetic nephropathy: the challenges of botanical product research.

PMID- 23141997
TI  - Influenza and pneumococcal vaccination in dialysis patients: merely a shot in the
      arm?

PMID- 23141998
TI  - Calcidiol deficiency in CKD patients: the role of reduced liver synthesis.

PMID- 23142000
TI  - Quiz page December 2012: bilateral kidney enlargement and acute kidney injury in
      a patient with HIV infection.

PMID- 23142001
TI  - Exploring the limits of broadband 90 degrees  and 180 degrees  universal rotation
      pulses.
AB  - 90 degrees  and 180 degrees  universal rotation (UR) pulses are two of the most
      important classes of pulses in modern NMR spectroscopy. This article presents a
      systematic study characterizing the achievable performance of these pulses as
      functions of bandwidth, pulse length, and tolerance to B(1)-field
      inhomogeneity/miscalibration. After an evaluation of different quality factors
      employed in pulse design algorithms based on optimal control theory, resulting
      pulses are discussed in detail with a special focus on pulse symmetry. The vast
      majority of resulting BURBOP (broadband universal rotations by optimal control)
      pulses are either fully symmetric or have one symmetric and one antisymmetric
      Cartesian rf component, where the importance of the first symmetry has not been
      demonstrated yet and the latter one matches the symmetry that results from a
      previously derived construction principle of universal rotation pulses out of
      point-to-point pulses [3]. Optimized BURBOP pulses are shown to perform better
      than previously reported UR pulses, resulting in shorter pulse durations for the
      same quality of broadband rotations. From a comparison of qualities of effective
      universal rotations, we find that the application of a single optimal refocusing
      pulse matches or improves the performance of two consecutive inversion pulses in
      INEPT-like pulse sequence elements of the same total duration.

PMID- 23142002
TI  - Radiofrequency microcoils for magnetic resonance imaging and spectroscopy.
AB  - Small radiofrequency coils, often termed "microcoils", have found extensive use
      in many areas of magnetic resonance. Their advantageous properties include a very
      high intrinsic sensitivity, a high (several MHz) excitation and reception
      bandwidth, the fact that large arrays can fit within the homogeneous volume of
      the static magnetic field, and the very high resonance frequencies (several GHz)
      that can be achieved. This review concentrates on recent developments in the
      construction of single and multiple RF microcoil systems, and new types of
      experiments that can be performed using such assemblies.

PMID- 23142003
TI  - Bladder wall fat on computed tomography with pathologic correlation.
AB  - OBJECTIVES: To determine the prevalence and significance of fat in the urinary
      bladder wall detectable by computed tomography (CT). METHODS: Retrospective
      review of 200 consecutive patients with noncontrast CT. Cystectomy specimen
      CT/pathologic correlation. RESULTS: CT-detectable fat in 30 (15%) patients was
      significantly more predominant in men (P=.003) and in patients with past renal
      stones (P<.001). Urinary tract infections were significantly less common in
      patients with bladder wall fat (P=.05). Pathologically, CT-detectable fat was
      submucosal. CONCLUSION: CT-detectable bladder wall fat is more common in men than
      women and in patients with a history of renal stones and urinary tract
      infections.

PMID- 23142004
TI  - Insights into the spin dynamics of a large anisotropy spin subjected to long
      pulse irradiation under a modified REDOR experiment.
AB  - Distance measurements between a spin-1/2 and a second spin bearing a large
      anisotropy are performed using a modified rotational echo double resonance
      (REDOR) experiment. By applying pairs of rotor-synchronized pi pulses on the
      detected spin and a single long pulse on the coupled spin the dipolar interaction
      is efficiently recoupled even at the sudden passage limit where both adiabaticity
      and the hard pulse approximation are not valid. In this manuscript we derive the
      theoretical basis for analyzing the behavior of single crystallites in order to
      gain insight into the mechanism of dipolar recoupling, and in order to find
      conditions for optimizing the experiment. The use of reduced time and frequency
      variables show that the signal depends on the ratios of the radio frequency
      strength nu(1) and the anisotropy, either the CSA (nu(sigma)) or the quadrupolar
      interaction (nu(Q)), with respect to the spinning frequency nu(R). We derive
      expressions for the contribution of individual crystallites to the signal arising
      from the different frequencies mnu(d) (m=0,1...2S) associated with the dipolar
      interaction and show that they result in a non-random distribution of
      intensities. For a spin-1/2 with a large CSA (up to 1MHz and more) we show using
      calculations and simulations that the result is a recoupling signal that takes
      maximal values DeltaS/S(0) of ~0.6-0.7, beyond the saturation limit of 0.5,
      defined by equal contribution of all transitions. For a spin-3/2 we show that at
      certain conditions the non-random scrambling may result in an apparent saturation
      like behavior. In all cases large RF amplitudes are not necessarily required for
      obtaining efficient recoupling. (13)C-(11)B LA-REDOR (Low-Alpha/Low-rf-Amplitude
      REDOR) dipolar recoupling experiments on 4-methoxyphenylboronic acid were
      performed following optimization of the spinning rates suitable for low amplitude
      radio-frequency power levels and show that efficient recoupling can be obtained
      for a spin-3/2, and that distance determination is not very strongly dependent on
      the actual value of the quadrupolar coupling constant.

PMID- 23142005
TI  - Observational study on the efficacy of adalimumab for the treatment of ulcerative
      colitis and predictors of outcome.
AB  - BACKGROUND: Information on efficacy and predictors of response to adalimumab in
      ulcerative colitis (UC) clinical practice is limited. AIM: Assessment of response
      to adalimumab and its predictors in an observational cohort study. METHODS:
      Retrospective cohort study based on data obtained from ENEIDA registry. All
      patients diagnosed with UC treated with adalimumab were included. Response to
      adalimumab was evaluated at weeks 12, 28, and 54 according to the partial Mayo
      score, and requirement of colectomy until end of follow-up. RESULTS: 48 patients
      with UC treated with adalimumab were included; 39 (81.3%) had previously received
      infliximab. Response rates at weeks 12, 28 and 54 were 70.8%, 43.2% and 35%
      respectively. Response to prior treatment with infliximab was the only predictive
      factor of response to adalimumab at week 12, which was obtained in 90% of
      infliximab remitters, 53.8% of responders and 33.3% of primary non-responders
      (p=0.01). Colectomy was required in 11 patients (22.9%), after a mean time of 205
      days. The only clinical independent predictor of colectomy was non-response to
      adalimumab at week 12: colectomy rates were 5/34 (14.7%) in responders and 6/14
      (42.9%) in non-responders (p=0.035), time free of colectomy was significantly
      reduced in non-responders (p=0.01). Adalimumab withdrawal due to adverse events
      occurred in 4.2% of patients. CONCLUSION: This study shows that adalimumab is an
      effective treatment in patients with UC. If used as a second anti-TNF, previous
      achievement of remission with the first anti-TNF predicts response, and failure
      to achieve response at week 12 predicts colectomy.

PMID- 23142006
TI  - Proteomic profiles of soluble proteins from the esophageal gland in female
      Meloidogyne incognita.
AB  - Meloidogyne incognita can infect multiple plant species. Proteins synthesized in
      the esophageal glands and secreted through the stylet of plant parasitic
      nematodes play critical roles in the plant-nematode interactions. Female M.
      incognita live for approximately 15days, embedded in a host plant, but their
      esophageal gland proteins have not yet been comprehensively analyzed. In this
      study, a new bacterium-contamination-resistant method for collecting soluble
      proteins from esophageal gland cells (SPEGC) of female M. incognita was
      established. Approximately 5MUg of freeze-dried proteins could be extracted from
      150 female M. incognita. Bands of a one-dimensional SDS-polyacrylamide gel were
      excised after electrophoresis of 20MUg of protein and were analyzed. Two hundred
      and forty-six proteins from SPEGC of female M. incognita were identified by LC
      MS/MS. Gene Ontology analysis suggests that many of the secreted proteins are
      involved in protein or carbohydrate metabolism and proteolysis. Some of the SPEGC
      (46.3%) were predicted to be secreted through classical or non-classical
      secretory pathways. The described method presents a new approach for the
      identification of proteins stored in SPEGC of an important plant parasitic
      nematode. This global proteomic profile of SPEGC provides a basis for future
      studies to elucidate the functions of proteins secreted from female M. incognita
      on plant responses.

PMID- 23142007
TI  - Emergency medical services out-of-hospital scene and transport times and their
      association with mortality in trauma patients presenting to an urban Level I
      trauma center.
AB  - STUDY OBJECTIVE: We determine the association between emergency medical services
      (EMS) out-of-hospital times and mortality in trauma patients presenting to an
      urban Level I trauma center. METHODS: We conducted a secondary analysis of a
      prospective cohort registry of trauma patients presenting to a Level I trauma
      center during a 14-year period (1996 to 2009). Inclusion criteria were patients
      sustaining traumatic injury who presented to an urban Level I trauma center.
      Exclusion criteria were extrication, missing or erroneous out-of-hospital times,
      and intervals exceeding 5 hours. The primary outcome was inhospital mortality.
      EMS out-of-hospital intervals (scene time and transport time) were evaluated with
      multivariate logistic regression. RESULTS: There were 19,167 trauma patients
      available for analysis, with 865 (4.5%) deaths; 16,170 (84%) injuries were blunt,
      with 596 (3.7%) deaths, and 2,997 (16%) were penetrating, with 269 (9%) deaths.
      Mean age and sex for blunt and penetrating trauma were 34.5 years (68% men) and
      28.1 years (90% men), respectively. Of those with Injury Severity Score less than
      or equal to 15, 0.4% died, and 26.1% of those with a score greater than 15 died.
      We analyzed the relationship of scene time and transport time with mortality
      among patients with Injury Severity Score greater than 15, controlling for age,
      sex, Injury Severity Score, and Revised Trauma Score. On multivariate regression
      of patients with penetrating trauma, we observed that a scene time greater than
      20 minutes was associated with higher odds of mortality than scene time less than
      10 minutes (odds ratio [OR] 2.90; 95% confidence interval [CI] 1.09 to 7.74).
      Scene time of 10 to 19 minutes was not significantly associated with mortality
      (OR 1.19; 95% CI 0.66 to 2.16). Longer transport times were likewise not
      associated with increased odds of mortality in penetrating trauma cases; OR for
      transport time greater than or equal to 20 minutes was 0.40 (95% CI 0.14 to
      1.19), and OR for transport time 10 to 19 minutes was 0.64 (95% CI 0.35 to 1.15).
      For patients with blunt trauma, we did not observe any association between scene
      or transport times and increased odds of mortality. CONCLUSION: In this analysis
      of patients presenting to an urban Level I trauma center during a 14-year period,
      we observed increased odds of mortality among patients with penetrating trauma if
      scene time was greater than 20 minutes. We did not observe associations between
      increased odds of mortality and out-of-hospital times in blunt trauma victims.
      These findings should be validated in an external data set.

PMID- 23142008
TI  - Accuracy of point-of-care ultrasonography for diagnosis of elbow fractures in
      children.
AB  - STUDY OBJECTIVE: We determine the test performance characteristics for point-of
      care ultrasonography performed by pediatric emergency physicians compared with
      radiographic diagnosis of elbow fractures and compare interobserver agreement
      between enrolling physicians and an experienced pediatric emergency medicine
      sonologist. METHODS: This was a prospective study of children aged up to 21 years
      and presenting to the emergency department (ED) with elbow injuries requiring
      radiographs. Before obtaining radiographs, pediatric emergency physicians
      performed focused elbow ultrasonography. An ultrasonographic result positive for
      fracture at the elbow was defined as the pediatric emergency physician's
      determination of an elevated posterior fat pad or lipohemarthrosis of the
      posterior fat pad. All patients received an elbow radiograph in the ED and
      clinical follow-up. The criterion standard for fracture was fracture on initial
      or follow-up radiographs. RESULTS: One hundred thirty patients with a mean age of
      7.5 years were enrolled by 26 sonologists. Forty-three (33%) patients had a
      radiograph result positive for fracture. A positive elbow ultrasonographic result
      had a sensitivity of 98% (95% confidence interval [CI] 88% to 100%), specificity
      of 70% (95% CI 60% to 79%), positive likelihood ratio of 3.3 (95% CI 2.4 to 4.5),
      and negative likelihood ratio of 0.03 (95% CI 0.01 to 0.23) for fracture. The
      interobserver agreement (kappa) was 0.77. The use of elbow ultrasonography would
      reduce radiographs in 48% of patients but would miss 1 fracture. CONCLUSION:
      Point-of-care ultrasonography is highly sensitive for elbow fractures, and a
      negative ultrasonographic result may reduce the need for radiographs in children
      with elbow injuries. Elbow ultrasonography may be useful in settings in which
      radiography is not readily accessible or is time consuming to obtain.

PMID- 23142009
TI  - Lung T-cell responses to nontypeable Haemophilus influenzae in patients with
      chronic obstructive pulmonary disease.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by
      pulmonary inflammation that persists after the cessation of smoking. T cells have
      a major role in driving inflammation in patients with COPD and are activated by
      specific antigens to produce mediators, such as cytokines. The antigens that
      activate lung T cells have not been clearly defined. Nontypeable Haemophilus
      influenzae (NTHi) is the dominant bacterium isolated from the lungs of patients
      with COPD. OBJECTIVE: We sought to measure the response of lung tissue T cells to
      stimulation with NTHi. METHODS: We obtained lung tissue from 69 subjects having
      lobectomies for lung cancer. Of the group, 39 subjects had COPD, and 30 without
      COPD were classified as control subjects. The lung tissue was dispersed into
      single-cell suspensions and stimulated with live NTHi. Cells were labeled with
      antibodies for 5 important inflammatory mediators in patients with COPD and
      analyzed by using flow cytometry. RESULTS: NTHi produced strong activation of
      both TH cells and cytotoxic T cells in the COPD cohort. The COPD cohort had
      significantly higher levels of cells producing TNF-alpha, IL-13, and IL-17 in
      both T-cell subsets. When control subjects were divided into those with and
      without a significant smoking history and compared with patients with COPD, there
      was a progressive increase in the numbers of T cells producing cytokines from
      nonsmoking control subjects to smoking control subjects to patients with COPD.
      CONCLUSION: NTHi activates lung T cells in patients with COPD. This
      proinflammatory profibrotic response might be a key cause of inflammation in
      patients with COPD and has implications for treatment.

PMID- 23142010
TI  - Textural characteristics of model and natural bone tissues and interfacial
      behavior of bound water.
AB  - Water, as a probe liquid bound in model systems (highly disperse hydroxyapatite -
      protein composites as a model of the main components of bones) and rat bone
      tissues healthy and affected by osteoporosis occurred due to experimental
      Alzheimer's disease (EAD), has been investigated using low-temperature (1)H NMR
      spectroscopy, NMR cryoporometry, TG/DTG/DTA, DSC, and TG and DSC thermoporometry.
      The textural characteristics of these intact systems cannot be studied using the
      standard adsorption methods, but the cryoporometry and thermoporometry methods
      give these characteristics. The (1)H NMR spectra of water bound in model and
      natural bone tissues include signals, which can be assigned to strongly
      associated (typical) water (SAW, chemical shift of proton resonance delta(H)=5-6
      ppm) and weakly associated (atypical) water (WAW) at delta(H)=1-2 ppm.
      Contributions of SAW and WAW give information on textural organization of both
      model and natural bones. The influence of such co-adsorbates as HCl, CDCl(3),
      CD(3)CN, C(6)D(6), and (CD(3))(2)SO on the interfacial behavior and clustering of
      bound water depends on their polarity, amounts of components, and textural and
      structural features of the materials analyzed with the (1)H NMR spectroscopy and
      cryoporometry methods. According to the NMR cryoporometry data, the EAD causes an
      increase in nanoporosity of the bone tissues. The total porosity and the specific
      surface area of biostructures (accessible for water molecules and estimated using
      NMR cryoporometry and TG thermoporometry methods with a model of cylindrical
      pores) are larger for the EAD sample. Weakly polar chloroform-d has a significant
      influence on the organization of water in the bone tissue, and this effect is
      greater for the EAD sample as more porous material.

PMID- 23142011
TI  - Surfactant mediated charging of polymer particles in a nonpolar liquid.
AB  - We study the charging behavior of polystyrene and polymethyl methacrylate
      particles with different functional surface groups in water and in decane
      containing either ionic (AOT) or nonionic surfactant (Span 85). Electrophoretic
      mobilities in the nonpolar media are measured as a function of surfactant
      concentration and the applied electric field strength by phase analysis light
      scattering (PALS); acid-base characteristics of the particles and the surfactant
      are investigated via contact angle measurement and interfacial tensiometry, and
      the residual water content of the non-aqueous dispersions is assessed by Karl
      Fischer titration. The results suggest a competition of several mechanisms for
      particle charging in nonpolar media. At high concentrations of the nonionic
      surfactant, particle charging becomes insensitive to the functional surface
      groups responsible for charging in aqueous dispersions, but consistent with a
      charge transfer between the polymer surface and the surfactant due to acid-base
      interactions, which can be rationalized in terms of measurable acid-base
      parameters. By contrast, particle charging in nonpolar solutions of the ionic
      surfactant (with significantly larger amounts of residual water) suggests a
      strong influence of surface headgroup ionization, and of dissociated surfactants
      adsorbed to the particle surface.

PMID- 23142012
TI  - Influence of the addition of transition metals (Cr, Zr, Mo) on the properties of
      MnOx-FeOx catalysts for low-temperature selective catalytic reduction of NOx by
      Ammonia.
AB  - The co-precipitation and citric acid methods were employed to prepare MnO(x)
      FeO(x) catalysts for the low-temperature selective catalytic reduction (SCR) of
      NO(x) by ammonia. It was found that the Mn-Fe (CP) sample obtained from the co
      precipitation method, which exhibited low crystalline of manganese oxides on the
      surface, high specific surface area and abundant acid sites at the surface, had
      better catalytic activity. The effects of doping different transition metals (Mo,
      Zr, Cr) in the Mn-Fe (CP) catalysts were further investigated. The study
      suggested that the addition of Cr can obviously reduce the take-off temperature
      of Mn-Fe catalyst to 90 degrees C, while the impregnation of Zr and Mo raised
      that remarkably. The texture and micro-structure analysis revealed that for the
      Cr-doped Mn-Fe catalysts, the active components had better dispersion with less
      agglomeration and sintering and the largest BET surface specific area. In situ
      FTIR study indicated that the addition of Cr can increase significantly the
      surface acidity, especially, the Lewis acid sites, and promote the formation of
      the intermediate -NH(3)(+). H(2)-TPR results confirmed the better low-temperature
      redox properties of Mn-Fe-Cr.

PMID- 23142013
TI  - Adsorption of trimethyl phosphate and triethyl phosphate on dry and water pre
      covered hematite, maghemite, and goethite nanoparticles.
AB  - Adsorption of trimethyl phosphate (TMP) and triethyl phosphate (TEP) on well
      characterized nanoparticles of hematite (alpha-Fe(2)O(3)), maghemite (gamma
      Fe(2)O(3)), and goethite (alpha-FeOOH) has been studied by in situ diffuse
      reflectance infrared Fourier transform spectroscopy (DRIFTS), 2D correlation
      DRIFTS analysis, and X-ray photoelectron spectroscopy (XPS) on dry and water pre
      covered surfaces. It is shown that, at room temperature and low coverage, both
      TMP and TEP coordinate to Lewis acid Fe sites through the O phosphoryl atom on
      hematite and maghemite, while hydrogen bonding to Bronstedt acid surface OH
      groups dominates on goethite. At room temperature, slow dissociation of TMP
      occurs on the iron (hydr)oxide nanoparticles, whereby a methoxy group is
      displaced to form surface methoxy, leaving adsorbed dimethyl phosphate (DMP).
      Methoxy is further decomposed to formate, suggesting an oxidative degradation
      pathway in synthetic air on the oxide particles. Relatively, larger amounts of
      DMP and surface methoxy form on maghemite, while more formate is produced on
      hematite. Upon TMP adsorption on dry goethite nanoparticles, no oxidation surface
      products were detected. Instead, a slow TMP hydrolysis pathway is observed,
      yielding orthophosphate. It is found that pre-adsorbed water stimulates the
      hydrolysis of TMP. In contrast to TMP, TEP adsorbs molecularly on all iron
      hydr(oxide) nanoparticles. This is attributed to the longer aliphatic chain,
      which stabilizes the loss of charge on the methoxy CO bonds by charge
      redistribution upon phosphoryl O coordination to Fe surface atoms. The presented
      results implicate different reactivity depending on specific molecular structure
      of the organophosphorus compound (larger functional groups can compensate loss of
      charge due to surface coordination) and iron (hydr)oxide surface structure
      (exposing Lewis acid or Bronstedt acid sites).

PMID- 23142014
TI  - Effects of a neurodynamic sliding technique on hamstring flexibility in healthy
      male soccer players. A pilot study.
AB  - PURPOSE: To compare the short-term effects of a neurodynamic sliding technique
      versus control condition on hamstring flexibility in healthy, asymptomatic male
      soccer players. SUBJECTS: Twenty-eight young male soccer players from Palencia,
      Spain (mean age 20.7 yrs +/- 1.0, range 19-22) with decreased hamstring muscle
      flexibility. METHODS: Subjects were randomly assigned to one of two groups:
      neurodynamic sliding intervention or no intervention control. Each subject's
      dominant leg was measured for straight leg raise (SLR) range of motion (ROM) pre-
      and post-intervention. Subjects received interventions as per group allocation
      over a 1 week period. Data were analyzed with a 2 (intervention: neurodynamic and
      control) * 2 (time: pre and post) factorial ANOVA with repeated measures and
      appropriate post-hoc analyses. RESULTS: A significant interaction was observed
      between intervention and time for hamstring extensibility, F(1,26) = 159.187, p <
      .0005. There was no difference between the groups at the start, p = .743;
      however, at the end of the study, the groups were significantly different with
      more range of motion in the group that received neurodynamic interventions, p =
      .001. The group that received neurodynamic interventions improved significantly
      over time (p < .001), whereas the control group did not (p = .684). CONCLUSION:
      Findings suggest that a neurodynamic sliding technique can increase hamstring
      flexibility in healthy, male soccer players.

PMID- 23142016
TI  - Effects of acute nicotine on somatosensory change-related cortical responses.
AB  - Nicotine is known to have enhancing effects on some aspects of attention and
      cognition. As for the pre-attentive processes of detecting sensory changes,
      nicotine has significant effects on the auditory and visual systems implying that
      its pre-attentive effect is common among sensory modalities. The purpose of the
      present study was to elucidate whether acute nicotine administration has
      enhancing effects in the somatosensory system. Change-related cortical activity
      in response to an abrupt increase in stimulus intensity was recorded using
      magnetoencephalography. The test stimulus consisted of standard electrical pulses
      at 100 Hz for 500 ms applied to the dorsum of the left hand followed by 0.7-mA
      stronger pulses for 300 ms. Nicotine was administered in a gum (4 mg of
      nicotine). Eleven healthy nonsmokers were tested with a double-blind and placebo
      controlled design. Effects of nicotine on the cortical response in the primary
      (S1) and secondary (S2) somatosensory cortices were investigated. Results showed
      that nicotine failed to affect the S1 response while it significantly increased
      the amplitude of S2 activity in the hemisphere ipsilateral to the stimulation,
      and shortened the peak latency of S2 activity in both hemispheres. Since cortical
      responses in the present study represent a pre-attentive automatic process to
      encode new somatosensory events, the results suggest that nicotine can exert
      beneficial cognitive effects without a direct impact on attention and that the
      effect of nicotine on the automatic change-detecting system is common across
      sensory modalities.

PMID- 23142017
TI  - Three-month treatment with pioglitazone reduces circulating C1q-binding
      adiponectin complex to total-adiponectin ratio, without changes in body mass
      index, in people with type 2 diabetes.
AB  - We measured circulating C1q-binding adiponectin (C1q-APN) levels before and after
      3-month treatment with pioglitazone in people with type 2 diabetes. The results
      indicate 3-month treatment with pioglitazone reduces circulating levels of C1q
      APN/total-adiponectin ratio without changes in body mass index.

PMID- 23142018
TI  - The expression of heterochromatin protein 1alpha/beta in the kidney tumors: a
      microarray immunohistochemical study.
AB  - Kidney tumors of various types may behave differently and have different
      prognosis. Due to some overlapping morphological features and immunohistochemical
      staining pattern, they may pose diagnostic challenge. Therefore, it is necessary
      to explore additional immunohistochemical stains to help in subclassifying these
      epithelial neoplasms. Tissue microarrays of 20 cases each of renal cell
      carcinomas (RCC) of clear cell, chromophobe, and papillary variants and
      oncocytoma were constructed and used to test the heterochromatin-associated
      protein (HP) 1alpha/beta expression. HP-1alpha/beta showed strong nuclear
      staining. Expression of HP-1alpha/beta was found mostly in papillary RCC (79%)
      and oncocytoma (75%) but less in chromophobe (30%) and clear cell RCCs (35%). HP
      1alpha/beta may be useful in the differential diagnosis of renal tumors,
      especially in the differentiation of chromophobe RCC and oncocytoma.

PMID- 23142019
TI  - Spectrum of nontumoral renal pathologies in tumor nephrectomies: nontumoral renal
      parenchyma changes.
AB  - Non-neoplastic changes are not rarely seen in renal parenchyma of nephrectomy
      specimens removed for primary renal neoplasms. These changes often involve both
      kidneys, thus causing impairment of renal function, reducing patient's quality of
      life and sometimes threatening it. Renal tissue accompanying the tumor provides
      an opportunity in order to evaluate these changes. However, the clinician should
      make available clinical and laboratory findings involving renal functions of the
      patient to the pathologist. It is also important that the pathologist must have
      appropriate knowledge and experience in nephropathology. In this study, we aimed
      to correlate these changes with the clinical data and make inquiries regarding
      our experience with nonneoplastic kidney pathology. Consecutive 403 nephrectomy
      specimens with primary renal neoplasms submitted to our department between 2003
      and 2009 were re-examined. Twenty-three nephrectomy materials from 21 patients
      had non-neoplastic changes, 2 of which were bilateral. Patient follow-up data
      were obtained from electronic medical records. Of all cases, eight had diabetic
      nephropathy; 2, amyloidosis; 5, segmental proliferative and/or sclerotic
      glomerulonephritis; and 6, cystic renal changes. These findings were seen in 5%
      of nephrectomy specimens diagnosed as clear cell renal cell carcinoma (RCC),
      chromophobe cell RCC and oncocytoma, whereas this rate was two times higher in
      nephrectomy specimens with papillary RCC. Most patients with renal failure who
      were diagnosed with clear cell carcinoma died within the first two years. Despite
      limited number of cases in our series, prognosis of cases with clear cell RCC
      were poorer. Consequently, we think that non-neoplastic changes should be
      reported along with the details regarding the tumor in order to achieve best
      treatment planning.

PMID- 23142020
TI  - A soluble guanylate cyclase stimulator, BAY 41-8543, preserves right ventricular
      function in experimental pulmonary embolism.
AB  - Pulmonary embolism (PE) increases pulmonary vascular resistance, causing right
      ventricular (RV) dysfunction, and poor clinical outcome. Present studies test if
      the soluble guanylate cyclase stimulator BAY 41-8543 reduces pulmonary vascular
      resistance and protects RV function. Experimental PE was induced in anesthetized,
      male Sprague-Dawley rats by infusing 25 MUm polystyrene microspheres (1.95
      million/100 g body wt, right jugular vein) producing moderate PE. Pulmonary
      artery vascular resistance, estimated as RVPSP/CO, increased 3-fold after 5 h of
      PE. Treatment with BAY 41-8543 (50 MUg/kg, I.V.; given at the time of PE
      induction) normalized this index by reducing RVPSP and markedly increasing CO,
      via preservation of heart rate and stroke volume. Ex vivo RV heart function
      showed minimal changes at 5 h of PE, but decreased significantly after 18 h of
      PE, including peak systolic pressure (PSP, Control 39 +/- 1 mmHg vs. 19 +/- 3
      PE), +dP/dt (1192 +/- 93 mmHg/s vs. 444 +/- 64) and -dP/dt (-576 +/- 60 mmHg/s
      vs. -278 +/- 40). BAY 41-8543 significantly improved all three indices of RV
      heart function (PSP 35 +/- 3.5, +dP/dt 1129 +/- 100, -dP/dt -568 +/- 87).
      Experimental PE produced increased PVR and RV dysfunction, which were ameliorated
      by treatment with BAY 41-8543. Thus, there is vasodilator reserve in this model
      of experimental PE that can be exploited to reduce the stress upon the heart and
      preserve RV contractile function.

PMID- 23142021
TI  - Are success and survival rates of early implant placement higher than immediate
      implant placement?
AB  - Immediate placement refers to the placement of an implant into a tooth socket at
      the time of extraction; early placement refers to the placement of an implant
      after substantial gingival healing, but before any clinically significant bone
      fill occurs within the socket. This study evaluated the success and survival
      rates of implants following immediate and early placement. 50 implants were
      placed in 36 patients. 26 immediate (group I) and 24 early placements (group II)
      were performed. Pain or tenderness with function, mobility, radiographic bone
      loss from initial surgery and exudate history were evaluated. Mean vertical bone
      loss in the immediate placement group was 0.55 mm and 0.80 mm in the early
      placement group. The survival rate for the immediate placement group was 96.16%
      with 51.6 months follow-up and in the early placement group was 100% with 61.9
      months follow-up. The results of this study suggest that although the success and
      survival rates of early placed implants were a little higher and the follow up
      period was longer than immediately placed implants, the difference was not
      remarkable. In conclusion, both implant insertion techniques are safe and
      reliable procedures with considerably high survival rates.

PMID- 23142022
TI  - An enhanced Text4Baby program: capturing teachable moments throughout pregnancy.

PMID- 23142023
TI  - MRI and CT appearances in metabolic encephalopathies due to systemic diseases in
      adults.
AB  - The term encephalopathy refers to a clinical scenario of diffuse brain
      dysfunction, commonly due to a systemic, metabolic, or toxic derangement. Often
      the clinical evaluation is unsatisfactory in this scenario and imaging plays an
      important role in the diagnosis, assessment of treatment response, and
      prognostication of the disorder. Hence, it is important for radiologists to be
      familiar with the imaging features of some relatively frequently acquired
      metabolic encephalopathies encountered in the hospital setting. This study
      reviews the computed tomography (CT) and magnetic resonance imaging (MRI)
      features of a number of metabolic encephalopathies that occur as part of systemic
      diseases in adults. The following conditions are covered in this review:
      hypoglycaemic encephalopathy, hypoxic ischaemic encephalopathy, non-ketotic
      hyperglycaemia, hepatic encephalopathy, uraemic encephalopathy, hyperammonaemic
      encephalopathy, and posterior reversible encephalopathy syndrome. MRI is the
      imaging method of choice in evaluating these conditions. Due to their high
      metabolic activity, bilateral basal ganglia changes are evident in the majority
      of cases. Concurrent imaging abnormalities in other parts of the central nervous
      system often provide useful diagnostic information about the likely underlying
      cause of the encephalopathy. Besides this, abnormal signal intensity and
      diffusion restriction patterns on MRI and MR spectroscopy features may provide
      important clues as to the diagnosis and guide further management. Frequently, the
      diagnosis is not straightforward and typical imaging features require correlation
      with clinical and laboratory data for accurate assessment.

PMID- 23142024
TI  - 320-detector row CT angiography for detection and evaluation of intracranial
      aneurysms: comparison with conventional digital subtraction angiography.
AB  - AIM: To compare the diagnostic performance of 320-detector row computed
      tomographic angiography (CTA) with digital subtraction angiography (DSA) for the
      detection and characterization of intracranial aneurysms. MATERIALS AND METHODS:
      Fifty-two consecutive patients with non-traumatic subarachnoid haemorrhage (SAH)
      and suspected intracranial aneurysms were evaluated from January 2009 to October
      2011. All underwent both 320-detector row volume CTA examination and DSA. CTA
      volume data were transmitted to a VITREA workstation and two physicians with
      experience in diagnostic imaging of the nervous system independently carried out
      image post-processing and assessed the results. The three-dimensional (3D) CTA
      and DSA images were assessed using intraoperative findings as the reference
      standard. RESULTS: In 52 patients, 54 aneurysms were detected; 48 patients
      underwent surgery for 50 aneurysms. The overall sensitivity, specificity, and
      accuracy of 3D CTA were 96.3, 100, and 94.6%, respectively. Meanwhile, the
      overall sensitivity, specificity, and accuracy of DSA were 98.1, 98.1, and 95.1%,
      respectively. For aneurysms less than 3 mm, the sensitivity, specificity, and
      accuracy of 3D CTA were 81.8, 100, and 93.3%, respectively. The sensitivity,
      specificity, and accuracy of DSA for small aneurysms were 90.9, 100, and 96.2%,
      respectively. 3D CTA was superior to DSA in demonstrating aneurysmal
      calcification, parent artery, and surrounding vascular anatomy. CONCLUSIONS: 3D
      CTA is a highly sensitive, specific, and non-invasive imaging method for
      diagnosis and evaluation of intracranial aneurysms. It also allows for precise
      depiction of aneurysm morphology. Therefore, 320-detector row CTA may be used as
      an alternative to DSA as a first-line imaging technique in patients with SAH.

PMID- 23142025
TI  - Transversus abdominis plane (TAP) catheters inserted under direct vision in the
      donor site following free DIEP and MS-TRAM breast reconstruction: a prospective
      cohort study of 45 patients.
AB  - INTRODUCTION: The transversus abdominis plane (TAP) block is a peripheral nerve
      block of T6-L1 intercostal nerves of the abdominal wall. The purpose of this
      study was to evaluate the usefulness of intermittent TAP blockade for the first
      two postoperative days following free muscle sparing-transverse rectus abdominis
      muscle (MS-TRAM) or deep inferior epigastric perforator (DIEP) flap
      reconstruction of the breast. Therapeutic--Level II evidence. MATERIAL AND
      METHODS: This prospective cohort consisted of 45 consecutive patients who
      underwent DIEP or MS-TRAM free-flap breast reconstruction. Intra-operatively, a
      multi-orifice epidural catheter was inserted under direct vision into the TAP.
      Ten millilitres of 0.25% bupivacaine was injected into each TAP catheter every 12
      h until removal on day 3. The control group consisted of 80 consecutive patients
      who underwent free MS-TRAM or DIEP free-flap breast reconstructions by the same
      two surgeons without TAP block. Postoperatively, both groups had patient
      controlled analgesia (PCA) and the primary outcome was intravenous (IV) PCA
      opioid consumption in the first 48 h. RESULTS: There were no complications
      associated with using TAP catheters. The 48-h PCA-delivered opioid requirement
      was significantly less (p<0.001) in the TAP block group (17.10+/-17.23 mg IV
      morphine equivalent) compared to the control group (48.44+/-39.53 mg).
      CONCLUSION: Intermittent delivery of bupivacaine through the TAP block
      significantly reduced postoperative parenteral opioid requirements following free
      MS-TRAM or DIEP flap reconstruction of the breast. This is the first report of
      the TAP block being inserted under direct vision to provide postoperative
      analgesia at the abdominal flap donor site following microsurgical breast
      reconstruction.

PMID- 23142026
TI  - MicroRNA-1 targets Slug and endows lung cancer A549 cells with epithelial and
      anti-tumorigenic properties.
AB  - MicroRNA-1 (miR-1) has recently been suggested to function as a tumor suppressor.
      Its functional relevance was assessed by exploring structural and tumorigenic
      properties of lung cancer A549 cells stably transduced with retrovirus containing
      pre-miR-1. A549 cells overexpressing miR-1 exhibited a significant morphological
      change from a mesenchymal to an epithelial phenotype characterized by cell
      polarization and intercellular junctions. The cells showed increased expression
      of E-cadherin, which colocalized with cortical actin filaments and vinculin to
      form typical adherens junction at the apical regions of intercellular borders.
      Additionally, they exhibited occludin-positive tight junctions at similar apical
      regions. Moreover, their migratory and invasive activities were inhibited, and
      their sensitivity to doxorubicin was increased slightly compared to control mock
      infected cells. These structural and tumorigenic properties induced by miR-1 were
      associated with the reduced expression of Slug, which was a transcriptional
      repressor of E-cadherin or an inducer of epithelial-to-mesenchymal transition.
      Consistently, Slug was identified as a miR-1 target by bioinformatics and a
      luciferase reporter assay with plasmids containing luciferase-Slug 3'UTR.
      Collectively, the data presented here suggest that re-expression of miR-1 may be
      an effective therapy that prevents cancer malignancy by converting cells from a
      mesenchymal phenotype to an epithelial phenotype via the downregulation of Slug.

PMID- 23142027
TI  - Identification of ZNF395 as a novel modulator of adipogenesis.
AB  - Adipogenesis is the process of cell differentiation by which mesenchymal stem
      cells (MSC) become adipocytes. Investigating the transcriptional regulatory
      process during adipogenesis may provide strategies to prevent obesity and other
      metabolic disorders. In recent years, numerous zinc finger proteins (ZFPs) have
      been implicated in regulating differentiation and cell fate determination. To
      investigate the regulatory role of ZFPs involved in adipogenesis, we performed
      genome-wide microarray expression profiling of an adipogenesis time series.
      Particularly focusing on the transiently responsive ZFPs, we identified and
      characterized the functional role of ZNF395 in adipogenesis. A systematic
      ablation of the ZNF395 transcript during adipogenesis revealed 40% reduction of
      adipocytes when compared to control. Furthermore, the number of adipocytes as
      well as the expression of key adipocyte markers were greatly induced when MSC
      were co-transduced with ZNF395 and PPARG2. To further elucidate the functional
      role of ZNF395 during adipogenesis, we attempted to trans-differentiate human
      dermal fibroblasts with PPARG2. The test remarkably revealed that ZNF395 in
      conjunction with PPARG2 greatly induced adipogenesis from dermal fibroblasts when
      compared to PPARG2 alone. These loss and gain of function experiments firmly
      establish that ZNF395 coordinate the transcriptional regulatory pathway with
      PPARG2, which may be necessary for the genesis of adipocytes.

PMID- 23142028
TI  - Cytoskeleton of cortical astrocytes as a target to proline through oxidative
      stress mechanisms.
AB  - Hyperprolinemia is an inherited disorder of proline (Pro) metabolism and patients
      affected by this disease may present neurological manifestations. However, the
      mechanisms of neural excitotoxicity elicited by hyperprolinemia are far from
      being understood. Considering the pivotal role of cytoskeletal remodeling in
      several neurodegenerative pathologies and the potential links between
      cytoskeleton, reactive oxygen species production and cell death, the aim of the
      present work was to study the effects of Pro on astrocyte and neuron cytoskeletal
      remodeling and the possible oxidative stress involvement. Pro induced a shift of
      actin cytoskeleton in stress fibers together with increased RhoA immunocontent
      and ERK1/2 phosphorylation/activation in cortical astrocytes. Unlike astrocytes,
      results evidenced little susceptibility of neuron cytoskeleton remodeling, since
      Pro-treated neurons presented unaltered neuritogenesis. We observed increased
      hydrogen peroxide production characterizing oxidative stress together with
      decreased superoxide dismutase (SOD) and catalase (CAT) activities in cortical
      astrocytes after Pro treatment, while glutathione peroxidase (GSHPx) activity
      remained unaltered. However, coincubation with Pro and Trolox/melatonin prevented
      decreased SOD and CAT activities in Pro-treated astrocytes. Accordingly, these
      antioxidants were able to prevent the remodeling of the actin cytoskeleton, RhoA
      increased levels and ERK1/2 phosphorylation in response to high Pro exposure.
      Taken together, these findings indicated that the cytoskeleton of cortical
      astrocytes, but not of neurons in culture, is a target to Pro and such effects
      could be mediated, at least in part, by redox imbalance, RhoA and ERK1/2
      signaling pathways. The vulnerability of astrocyte cytoskeleton may have
      important implications for understanding the effects of Pro in the neurotoxicity
      linked to inborn errors of Pro metabolism.

PMID- 23142029
TI  - Neuroprotection and other novel therapies for glaucoma.

PMID- 23142030
TI  - Comparative study of genotoxicity and tissue distribution of nano and micron
      sized iron oxide in rats after acute oral treatment.
AB  - Though nanomaterials (NMs) are being utilized worldwide, increasing use of NMs
      have raised concerns over their safety to human health and environment. Iron
      oxide (Fe(2)O(3)) NMs have important applications. The aim of this study was to
      assess the genotoxicity of Fe(2)O(3)-30nm and Fe(2)O(3)-bulk in female Wistar
      rats. Fe(2)O(3)-30nm was characterized by using transmission electron microscopy,
      dynamic light scattering, laser Doppler velocimetry and surface area analysis.
      The rats were treated orally with the single doses of 500, 1000, 2000mg/kg bw of
      Fe(2)O(3)-30nm and Fe(2)O(3) -bulk. The genotoxicity was evaluated at 6, 24, 48
      and 72h by the comet assay in leucocytes, 48 and 72h by micronucleus test (MNT)
      in peripheral blood cells, 18 and 24h by chromosomal aberration (CA) assay and 24
      and 48h by MNT in bone marrow cells. The biodistribution of iron (Fe) was carried
      out at 6, 24, 48 and 72h after treatment in liver, spleen, kidney, heart, brain,
      bone marrow, urine and feces by using atomic absorption spectrophotometry. The %
      tail DNA, frequencies of micronuclei and CAs were statistically insignificant
      (p>0.05) at all doses. These results suggest that Fe(2)O(3)-30nm and Fe(2)O(3)
      bulk was not genotoxic at the doses tested. Bioavailability of Fe was size and
      dose dependent in all the tissues from the groups exposed to Fe(2)O(3)-30nm.
      Fe(2)O(3) NMs were able to enter in the organs and the rats are biocompatible
      with much higher concentration of Fe. However, the accumulated Fe did not cause
      significant genotoxicity. This study provides additional knowledge about the
      toxicology of Fe(2)O(3) NMs.

PMID- 23142031
TI  - Cloning and characterization of two genes coding for the histone
      acetyltransferases, Elp3 and Mof, in brown planthopper (BPH), Nilaparvata lugens
      (Stal).
AB  - Histone acetylation is a vital mechanism for the post-translational modifications
      of chromatin components. Histone acetyltransferases (HATs) are critical elements
      that determine histone acetylation and regulate chromatin dynamics and gene
      expression. While histone acetyltransferases have been well studied in mammals
      and Drosophila melanogaster, information from agriculturally important insect
      pests is still limited. In our effort to understand the epigenetic mechanisms
      regulating development in the brown planthopper, Nilaparvata lugens (Stal)
      (Hemiptera: Geometroidea), a major rice pest in many parts of Asia, two full
      length cDNA sequences encoding HAT members of the GNAT and MYST family, namely
      NlElp3 and NlMof, respectively, were isolated and structurally and
      phylogenetically characterized. The NlElp3 contains an open reading frame (ORF)
      of 1656bp encoding a protein of 551 amino acids. The NlMof contains a 1353bp ORF
      encoding a protein of 450 amino acids. Sequence analysis showed that NlElp3
      contains GNAT-type HAT domain and Radical SAM domain, and NlMof contains
      chromodomain and MOZ-SAS acetyltransferase domain. Multiple sequence alignments
      showed that NlElp3 and NlMof have high amino acid sequence identity with other
      insect homologues. Expression analysis of the NlElp3 and NlMof revealed
      significant differences in mRNA expression levels among N. lugens developmental
      stages, suggesting that HAT activities of NlElp3 and NlMof may be controlled, at
      least in part, by their developmental regulation. Remarkably, the mRNA expression
      levels of NlElp3 and NlMof in female adults were significantly higher than that
      in male adults, supporting an important role for both genes in female
      reproductive function in N. lugens.

PMID- 23142032
TI  - [Recruitment difficulties for clinical trials in primary care. When sample size
      is not reached].

PMID- 23142033
TI  - Sending out an ExoS--eyes kept on Pseudomonas.

PMID- 23142034
TI  - The Toxoplasma MAG1 peptides induce sex-based humoral immune response in mice and
      distinguish active from chronic human infection.
AB  - To distinguish active from inactive/chronic infection in Toxoplasma gondii
      seropositive individuals, we have developed an enzyme-linked immunosorbent assay
      (ELISA) using specific peptides derived from Toxoplasma matrix antigen MAG1. We
      used this assay to measure matrix specific antibodies and pilot studies with
      infected mice established the validity of two peptides. The immune response
      against MAG1 occurs in about 12 days postinfection and displays a sex difference
      later on in mouse model, with males producing higher antibody titers than
      females. Serum samples from 22 patients with clinical toxoplasmosis and from 26
      patients with serological evidence of past exposure to Toxoplasma (more than one
      year infection history) were analyzed. Both MAG1 peptides detected antibodies
      significant frequently and robustly from active stage than from the chronic stage
      of toxoplasmosis. The results indicate that both MAG1 peptides may be used as a
      tool to differentiate active from inactive infection. It also may be considered
      in the design of potential vaccines in humans.

PMID- 23142035
TI  - Non-neutral evolution in non-LEE-encoded type III effectors of attaching and
      effacing Escherichia coli.
AB  - Attaching and effacing Escherichia coli (AEEC) employ type III secretion system
      (T3SS) to secrete effector proteins into host cells and regulate their function.
      Here we have investigated T3SS genes of AEEC for non-neutral evolution. Our
      analysis revealed non-neutral evolution in three genes (nleE1, nleB2 and nleD)
      which encode effector proteins. These genes are located outside the locus of
      enterocyte effacement (LEE). In general, non-LEE effector genes show greater
      deviation from neutral evolution than LEE effector genes. These results suggest
      that effector genes located outside LEE are under greater selection pressure than
      those present in LEE.

PMID- 23142036
TI  - Redundancy matters: flexible learning of multiple contingencies in infants.
AB  - Many objects and events can be categorized in different ways, and learning
      multiple categories in parallel often requires flexibly attending to different
      stimulus dimensions in different contexts. Although infants and young children
      often exhibit poor attentional control, several theoretical proposals argue that
      such flexibility can be achieved without selective attention. If this is the
      case, then even young infants should be able to learn multiple dimension-context
      contingencies in parallel. This possibility was tested in four experiments with
      14- and 22-month-olds. Learning of contingencies succeeded as long as there were
      multiple correlations between the context and the to-be-learned dimension. These
      findings suggest that infants can learn multiple dimension-context contingencies
      in parallel, but only when there is sufficient redundancy in the input.

PMID- 23142037
TI  - When it takes a bad person to do the right thing.
AB  - Three studies demonstrate that morally praiseworthy behavior can signal negative
      information about an agent's character. In particular, consequentialist decisions
      such as sacrificing one life to save an even greater number of lives can lead to
      unfavorable character evaluations, even when they are viewed as the preferred
      course of action. In Study 1, throwing a dying man overboard to prevent a
      lifeboat from sinking was perceived as the morally correct course of action, but
      led to negative aspersions about the motivations and personal character of
      individuals who carried out such an act. In Studies 2 and 3, a hospital
      administrator who decided not to fund an expensive operation to save a child
      (instead buying needed hospital equipment) was seen as making a pragmatic and
      morally praiseworthy decision, but also as deficient in empathy and moral
      character.

PMID- 23142038
TI  - Object location memory: integration and competition between multiple context
      objects but not between observers' body and context objects.
AB  - Five experiments examined the integration and competition between body and
      context objects in locating an object. Participants briefly viewed a target
      object in a virtual environment and detected whether the target object was moved
      or not after a 10 s interval. Experiments 1 and 2 showed that performance when
      both the observer body and the context objects were consistent across study and
      test was not better than the optimal sum of performances when either one was the
      only consistent cue across study and test. In Experiments 3 and 4, in the
      competition conditions, both the body and the context objects were reference
      points at learning but only one stayed consistent during test. In the no
      competition conditions, only the body or the context objects were the primary
      reference points in learning and it stayed consistent in test. Detection
      performance did not differ between these conditions. Experiment 5 demonstrated
      the integration and competition between context objects as a reference point.
      Detection performance based on all four context objects was better than the
      optimal sum of the performance based on two close context objects and the
      performance based on two far context objects; detection performance based on two
      context objects was better when there were only these two context objects during
      learning than when there were four context objects during learning. These results
      suggest that body-object (body-target) and interobject (context-target) vectors
      are encoded independently and combined at test in an optimal way. Body-object and
      interobject vectors are not encoded in an integrated way and encoding of them
      does not compete. By contrast multiple interobject vectors are encoded in an
      integrated way in addition to the representations of individual interobject
      vectors and encoding close interobject vectors and encoding far interobject
      vectors interfere with each other.

PMID- 23142039
TI  - Characterisation of two deletions involving NPC1 and flanking genes in Niemann
      Pick type C disease patients.
AB  - Niemann-Pick type C (NPC) disease is an autosomal recessive lysosomal disorder
      characterised by the accumulation of a complex pattern of lipids in the lysosomal
      late endosomal system. More than 300 disease-causing mutations have been
      identified so far in the NPC1 and NPC2 genes, including indel, missense, nonsense
      and splicing mutations. Only one genomic deletion, of more than 23 kb, has been
      previously reported. We describe two larger structural variants, encompassing
      NPC1 and flanking genes, as a cause of the disease. QMPSF, SNP inheritance and
      CytoScan(r) HD Array were used to confirm and further characterise the presence
      of hemizygous deletions in two patients. One of the patients (NPC-57) bore a
      previously described missense mutation (p.T1066N) and an inherited deletion that
      included NPC1, C18orf8 and part of ANKRD29 gene. The second patient (NPC-G1) had
      a 1-bp deletion (c.852delT; p.F284Lfs*26) and a deletion encompassing the
      promoter region and exons 1-10 of NPC1 and the adjacent ANKRD29 and LAMA3. This
      study characterised two novel chromosomal microdeletions at 18q11-q12 that cause
      NPC disease and provide insight into missing NPC1 mutant alleles.

PMID- 23142040
TI  - Accelerated aging of Asp 58 in alphaA crystallin and human cataract formation.
AB  - Racemisation of amino acids is one of the most abundant modifications in long
      lived proteins. In this study racemisation of Asp 58 in the small heat shock
      protein, alphaA crystallin, was investigated. In normal human lenses, levels of l
      isoAsp, d-isoAsp and d-Asp increased with age, such that by age 70 they accounted
      for approximately half of the total Asp at this site. Levels of d-isoAsp were
      significantly higher in all cataract lenses than age-matched normal lenses. The
      introduction of d-isoAsp in alphaA crystallin could therefore be associated with
      the development of cataract. Its more rapid formation in cataract lenses may
      represent an example of accelerated protein aging leading to a human age-related
      disease.

PMID- 23142041
TI  - Embryonic learning of vocal passwords in superb fairy-wrens reveals intruder
      cuckoo nestlings.
AB  - How do parents recognize their offspring when the cost of making a recognition
      error is high? Avian brood parasite-host systems have been used to address this
      question because of the high cost of parasitism to host fitness. We discovered
      that superb fairy-wren (Malurus cyaneus) females call to their eggs, and upon
      hatching, nestlings produce begging calls with key elements from their mother's
      "incubation call." Cross-fostering experiments showed highest similarity between
      foster mother and nestling calls, intermediate similarity with genetic mothers,
      and least similarity with parasitic Horsfield's bronze-cuckoo (Chalcites basalis)
      nestlings. Playback experiments showed that adults respond to the begging calls
      of offspring hatched in their own nest and respond less to calls of other wren or
      cuckoo nestlings. We conclude that wrens use a parent-specific password learned
      embryonically to shape call similarity with their own young and thereby detect
      foreign cuckoo nestlings.

PMID- 23142042
TI  - Pacemaker and plateau potentials shape output of a developing locomotor network.
AB  - BACKGROUND: During development, spinal networks undergo an intense period of
      maturation in which immature forms of motor behavior are observed. Such behaviors
      are transient, giving way to more mature activity as development proceeds. The
      processes governing age-specific transitions in motor behavior are not fully
      understood. RESULTS: Using in vivo patch clamp electrophysiology, we have
      characterized ionic conductances and firing patterns of developing zebrafish
      spinal neurons. We find that a kernel of spinal interneurons, the ipsilateral
      caudal (IC) cells, generate inherent bursting activity that depends upon a
      persistent sodium current (I(NaP)). We further show that developmental
      transitions in motor behavior are accompanied by changes in IC cell bursting:
      during early life, these cells generate low frequency membrane oscillations that
      likely drive "coiling," an immature form of motor output. As fish mature to
      swimming stages, IC cells switch to a sustained mode of bursting that permits
      generation of high-frequency oscillations during locomotion. Finally, we find
      that perturbation of IC cell bursting disrupts motor output at both coiling and
      swimming stages. CONCLUSIONS: Our results suggest that neurons with unique
      bursting characteristics are a fundamental component of developing motor
      networks. During development, these may shape network output and promote stage
      specific reconfigurations in motor behavior.

PMID- 23142043
TI  - Sumatran orangutans differ in their cultural knowledge but not in their cognitive
      abilities.
AB  - Animal cultures are controversial because the method used to isolate culture in
      animals aims at excluding genetic and environmental influences rather than
      demonstrating social learning. Here, we analyzed these factors in parallel in
      captivity to determine their influences on tool use. We exposed Sumatran
      orangutan (Pongo abelii) orphans from tool-using and non-tool-using regions
      (western swamps and eastern Langkat, respectively) that differed in both genetic
      and cultural backgrounds to a raking task and a honey-dipping task to assess
      their understanding of stick use. Orangutans from both regions were equally
      successful in raking; however, swamp orangutans were more successful than Langkat
      orangutans in honey dipping, where previously acquired knowledge was required. A
      larger analysis suggested that the Alas River could constitute a geographical
      barrier to the spread of this cultural trait. Finally, honey-dipping individuals
      were on average less than 4 years old, but this behavior is not observed in the
      wild before 6 years of age. Our results suggest first that genetic differences
      between wild Sumatran populations cannot explain their differences in stick use;
      however, their performances in honey dipping support a cultural differentiation
      in stick knowledge. Second, the results suggest that the honey-dippers were too
      young when arriving at the quarantine center to have possibly mastered the
      behavior in the wild individually, suggesting that they arrived with
      preestablished mental representations of stick use or, simply put, "cultural
      ideas."

PMID- 23142044
TI  - Transcription in the absence of histone H3.2 and H3K4 methylation.
AB  - Histone H3 proteins play fundamental roles in DNA packaging, gene transcription,
      and the transmission of epigenetic states. In addition to posttranslational
      modifications of their N termini, the use of H3 variants contributes to their
      regulatory repertoire. Canonical histone H3.2 is expressed during S phase and
      differs by four amino acid residues from the variant histone H3.3, which is
      synthesized in a cell-cycle-independent manner. Because H3.3 is enriched within
      actively transcribed loci, and because di- and trimethylation of H3 lysine 4 are
      hallmarks of chromatin at such sites in the genome, the H3.3K4 residue is
      considered to serve as the major regulatory determinant for the transcriptional
      state of a gene. Here we use genetic approaches in Drosophila to replace all 46
      gene copies of His3.2 with mutant derivatives and thereby demonstrate that
      canonical and variant H3 can functionally replace each other. Cells are able to
      divide and differentiate when H3.2 is entirely absent but replaced by S phase
      expressed H3.3. Moreover, although slowed down in their proliferative capacity,
      cells that code for a nonmethylatable residue instead of K4 in all canonical and
      variant H3 genes are competent to respond to major developmental signaling
      pathways by activating target gene expression. Hence, the presence of different
      H3 protein species is not essential in Drosophila and transcriptional regulation
      can occur in the complete absence of H3K4 methylation.

PMID- 23142045
TI  - Octopamine neurons mediate flight-induced modulation of visual processing in
      Drosophila.
AB  - BACKGROUND: Activity-dependent modulation of sensory systems has been documented
      in many organisms and is likely to be essential for appropriate processing of
      information during different behavioral states. However, the mechanisms
      underlying these phenomena remain poorly characterized. RESULTS: We investigated
      the role of octopamine neurons in the flight-dependent modulation observed in
      visual interneurons in Drosophila. The vertical system (VS) cells exhibit a boost
      in their response to visual motion during flight compared to quiescence.
      Pharmacological application of octopamine evokes responses in quiescent flies
      that mimic those observed during flight, and octopamine cells that project to the
      optic lobes increase in activity during flight. Using genetic tools to manipulate
      the activity of octopamine neurons, we find that they are both necessary and
      sufficient for the flight-induced visual boost. CONCLUSIONS: This study provides
      the first evidence that endogenous release of octopamine is involved in state
      dependent modulation of visual interneurons in flies.

PMID- 23142046
TI  - She1-mediated inhibition of dynein motility along astral microtubules promotes
      polarized spindle movements.
AB  - BACKGROUND: Cytoplasmic dynein motility along microtubules is critical for
      diverse cellular processes ranging from vesicular transport to nuclear envelope
      breakdown to mitotic spindle alignment. In yeast, we have proposed a regulated
      offloading model to explain how dynein motility drives microtubule sliding along
      the cortex, powering transport of the nucleus into the mother-bud neck [1, 2]:
      the dynein regulator She1 limits dynein offloading by gating the recruitment of
      dynactin to the astral microtubule plus end, a prerequisite for offloading to the
      cortex. However, whether She1 subsequently affects cortically anchored dynein
      activity during microtubule sliding is unclear. RESULTS: Using single-molecule
      motility assays, we show that She1 strongly inhibits dynein movement along
      microtubules, acting directly on the motor domain in a manner independent of
      dynactin. She1 has no effect on the motility of either Kip2, a kinesin that
      utilizes the same microtubule track as dynein, or human kinesin-1, demonstrating
      the specificity of She1 for the dynein motor. At single-molecule resolution, She1
      binds tightly to and exhibits diffusional behavior along microtubules. Diffusive
      She1 collides with and pauses motile dynein motors, prolonging their attachment
      to the microtubule. Furthermore, Aurora B/Ipl1 directly phosphorylates She1, and
      this modification appears to enhance the diffusive behavior of She1 along
      microtubules and its potency against dynein. In cells, She1 dampens productive
      microtubule-cortex interactions specifically in the mother compartment,
      polarizing spindle movements toward the bud cell. CONCLUSIONS: Our data reveal
      how inhibitory microtubule-associated proteins selectively regulate motor
      activity to achieve unidirectional nuclear transport and demonstrate a direct
      link between cell-cycle machinery and dynein pathway activity.

PMID- 23142047
TI  - Mucin biopolymers prevent bacterial aggregation by retaining cells in the free
      swimming state.
AB  - Many species of bacteria form surface-attached communities known as biofilms.
      Surrounded in secreted polymers, these aggregates are difficult both to prevent
      and eradicate, posing problems for medicine and industry. Humans play host to
      hundreds of trillions of microbes that live adjacent to our epithelia, and we are
      typically able to prevent harmful colonization. Mucus, the hydrogel overlying all
      wet epithelia in the body, can prevent bacterial contact with the underlying
      tissue. The digestive tract, for example, is lined by a firmly adherent mucus
      layer that is typically devoid of bacteria, followed by a second, loosely
      adherent layer that contains numerous bacteria. Here, we investigate the role of
      mucus as a principle arena for host-microbe interactions. Using defined in vitro
      assays, we found that mucin biopolymers, the main functional constituents of
      mucus, promote the motility of planktonic bacteria and prevent their adhesion to
      underlying surfaces. The deletion of motility genes, however, allows Pseudomonas
      aeruginosa to overcome the dispersive effects of mucus and form suspended
      antibiotic-resistant flocs, which mirror the clustered morphology of immotile
      natural isolates found in the cystic fibrosis lung mucus. Mucus may offer new
      strategies to target bacterial virulence, such as the design of antibiofilm
      coatings for implants.

PMID- 23142048
TI  - Proceedings of the French Arthroscopy Society. Editorial.

PMID- 23142049
TI  - Anterior cruciate ligament reconstruction in partial tear: selective anteromedial
      bundle reconstruction conserving the posterolateral remnant versus single-bundle
      anatomic ACL reconstruction: preliminary 1-year results of a prospective
      randomized study.
AB  - INTRODUCTION: Partial tears of the anterior cruciate ligament (ACL) are frequent.
      Conserving ACL remnants is central to the concept of anatomic, biomechanical and
      biological reconstruction. The interest of such conservation remains theoretical.
      The present hypothesis was that selective anteromedial (AM) bundle reconstruction
      is preferable to the standard single-bundle reconstruction in partial ACL tear.
      MATERIALS AND METHODS: A multicenter prospective randomized study recruited 54
      partial ACL tears operated on either by selective AM bundle reconstruction (Group
      1, n=29) or by standard anatomic single-bundle reconstruction (Group 2, n=25).
      All patients were clinically assessed on subjective and objective IKDC, Lysholm
      and KOOS scores, with a minimum 12 months' follow-up. Comparative pre- to
      postoperative anterior laxity was measured on the Rolimeter((r)) device, with
      statistical analysis of results. RESULTS: There were no significant preoperative
      differences between the two groups. All patients were followed-up at 6 months and
      1 year. Mean subjective IKDC scores for groups 1 and 2 respectively were 55.8 and
      56.8 preoperatively versus 86.2 and 85.7 at 1 year; Lysholm scores were 69.9 and
      71.1 versus 90.9 and 91.8. These inter-group differences were non-significant.
      Differential laxity for groups 1 and 2 respectively was 5.0mm (range, 2-10) and
      5.1mm (2-12) preoperatively (P=0.73), versus 1.2mm and 1.9 mm postoperatively
      (P=0.03). DISCUSSION AND CONCLUSION: In partial ACL tear, selective AM bundle
      reconstruction conserving the posterolateral bundle remnant provides clinical
      results comparable to the standard single-bundle technique, with better control
      of anterior laxity. Longer follow-up, however, will be needed to compare
      evolution in anterior and rotational laxity and in subjective results over time.

PMID- 23142050
TI  - Partial ACL reconstruction with preservation of the posterolateral bundle.
AB  - INTRODUCTION: Over the past decade, our understanding of the anterior cruciate
      ligament (ACL) has evolved considerably. Based on this knowledge, ACL
      reconstruction techniques have changed and selective reconstruction procedures
      have been developed for partial tears. Our hypothesis was that stability and
      function can be restored to the knee with selective bundle reconstruction of
      partial ACL tears and preservation of the residual fibers. MATERIALS AND METHODS:
      This was a multicenter retrospective study of 168 partial reconstructions of the
      anteromedial (AM) bundle of the ACL with preservation of the posterolateral (PL)
      bundle. All patients underwent a clinical evaluation based on the objective and
      subjective IKDC scores and the Lysholm score after a mean follow-up of 26 months
      (12-59 months). Preoperative and postoperative instrumental measurement of knee
      laxity was performed by arthrometer and/or by (Telos((r))) stress radiography.
      Statistical analysis and comparison was performed between pre- and postoperative
      results. RESULTS: The preoperative and postoperative subjective IKDC scores were
      63.7 and 90.5 at the final follow-up respectively (P<0.001). The preoperative and
      postoperative Lysholm scores were 80 and 95.5 respectively (P<0.001).
      Preoperatively, most patients were classified C on the objective IKDC score. At
      the final follow-up 92% of the patients were classified A or B (P<0.001).
      Differential preoperative laxity was 5.5mm (range: 0-14 mm) and 1.1mm (range: 0
      4mm) at the final follow-up (P<0.00001). DISCUSSION AND CONCLUSION: Our study
      confirms that selective reconstruction of the AM bundle of the ACL with
      preservation of the PL bundle restores stability and function to the knee.
      Special attention should be paid to the size of the graft used to avoid excess
      tissue in the intercondylar notch.

PMID- 23142052
TI  - Chemokine receptors CCR2 and CX3CR1 regulate skin fibrosis in the mouse model of
      cytokine-induced systemic sclerosis.
AB  - BACKGROUND: Skin fibrotic disorders such as systemic sclerosis (SSc) are
      characterized by an excessive accumulation of extracellular matrix (ECM), and
      develop under the influence of certain cytokines. We previously established a
      mouse model of skin fibrosis induced by exogenous application of cytokines. We
      have revealed that both the number of macrophages and the levels of macrophage
      chemoattractant protein-1 (MCP-1) mRNA positively correlate with the extent of
      skin fibrosis. Macrophages can be divided into two subsets, the first expressing
      CCR2, and the second expressing CX3CR1. OBJECTIVE: To elucidate the role of skin
      infiltrating macrophages based on CCR2 and CX3CR1 in this cytokine-induced murine
      fibrosis model. METHODS: We examined the amounts of collagen deposited in
      granulation tissues, the numbers of macrophages and the levels of several mRNA in
      wild type (WT) mice, CCR2(-/-) mice, and CX3CR1(-/-) mice during injections of
      transforming growth factor-beta (TGF-beta) followed by injections of connective
      tissue growth factor (CTGF). RESULTS: TGF-beta injection increased the
      expressions of MCP-1, fractalkine, CCR2 and CX3CR1 mRNA in WT mice. The
      overproduction of collagen induced by TGF-beta was significantly reduced by CCR2
      deficiency, while collagen contents induced by CTGF were restored to wild-type
      levels. In contrast, overproduction of collagen in CX3CR1-deficient mice
      decreased nearly 50% by both TGF-beta and CTGF stimulations. CONCLUSION: The
      involvement of CCR2/MCP-1 interaction (CCR2-dependent loop) was during the TGF
      beta phase. In contrast, the fractalkine/CX3CR1 interaction contributes to the
      initiation of fibrosis by TGF-beta and its maintenance by CTGF. Collectively, two
      subsets of macrophages both cooperatively and independently play important roles
      in the development of fibrosis.

PMID- 23142051
TI  - Convergent multi-miRNA targeting of ApoE drives LRP1/LRP8-dependent melanoma
      metastasis and angiogenesis.
AB  - Through in vivo selection of human cancer cell populations, we uncover a
      convergent and cooperative miRNA network that drives melanoma metastasis. We
      identify miR-1908, miR-199a-5p, and miR-199a-3p as endogenous promoters of
      metastatic invasion, angiogenesis, and colonization in melanoma. These miRNAs
      convergently target apolipoprotein E (ApoE) and the heat shock factor DNAJA4.
      Cancer-secreted ApoE suppresses invasion and metastatic endothelial recruitment
      (MER) by engaging melanoma cell LRP1 and endothelial cell LRP8 receptors,
      respectively, while DNAJA4 promotes ApoE expression. Expression levels of these
      miRNAs and ApoE correlate with human metastatic progression outcomes. Treatment
      of cells with locked nucleic acids (LNAs) targeting these miRNAs inhibits
      metastasis to multiple organs, and therapeutic delivery of these LNAs strongly
      suppresses melanoma metastasis. We thus identify miRNAs with dual cell
      intrinsic/cell-extrinsic roles in cancer, reveal convergent cooperativity in a
      metastatic miRNA network, identify ApoE as an anti-angiogenic and metastasis
      suppressive factor, and uncover multiple prognostic miRNAs with synergistic
      combinatorial therapeutic potential in melanoma.

PMID- 23142053
TI  - MicroRNA-29b contributes to DNA hypomethylation of CD4+ T cells in systemic lupus
      erythematosus by indirectly targeting DNA methyltransferase 1.
AB  - BACKGROUND: The mechanism of DNA hypomethylation in systemic lupus erythematosus
      (SLE) has not been fully elucidated. Recent studies showed that miR-29b could
      regulate DNA methylation by targeting the DNA methylation machinery. However, the
      role of miR-29b in T cell aberrant DNA hypomethylation of SLE still remains
      unclear. OBJECTIVE: In this study, we asked whether miR-29b regulate DNA
      methylation in lupus CD4+ T cells. METHODS: The miR-29b expression was analyzed
      by quantitative polymerase chain reaction (qPCR). Sp1, DNMT1, CD11a and CD70 mRNA
      and protein levels were determined by qPCR, Western-blotting and flow cytometry,
      respectively. The global DNA methylation levels were evaluated by the
      MethyflashTM DNA Methylation Quantification Kit. CD11a and CD70 promoter
      methyaltion levels were detected by bisulfate modification and methylation
      sensitive high resolution melting analysis. RESULTS: In SLE patients, the miR-29b
      levels were up-regulated as compared to healthy donors and its degree of
      overexpression was negatively correlated with sp1 and DNMT1 protein levels,
      respectively. Overexpression of miR-29b resulted in significant reduction of sp1
      and DNMT1 expression. Further analysis demonstrated that overexpression of miR
      29b in CD4+ T cells from healthy donors led to the DNA hypomethylation and up
      regulation of genes encoding CD11a and CD70, and inhibition of miR-29b expression
      in CD4+ T cells from patients with lupus caused reverse effects. CONCLUSION: Our
      study suggests that miR-29b negatively regulates DNMT1 expression by targeting
      sp1 in T cells. The overexpression of miR-29b contributes to the reduction of
      DNMT1 levels and thereby DNA hypomethylation in SLE. This finding provides
      potential novel strategies for therapeutic interventions.

PMID- 23142054
TI  - Perceptions of emergency nurses during the human swine influenza outbreak: a
      qualitative study.
AB  - INTRODUCTION: The primary aim of this study was to explore the perception of Hong
      Kong emergency nurses regarding their work during the human swine influenza
      pandemic outbreak. METHODS: In this exploratory, qualitative study, 10 emergency
      nurses from a regional hospital in Hong Kong were recruited using purposive
      sampling. Semi-structured, face-to-face individual interviews were conducted.
      Qualitative content analysis was utilized to analyze the transcripts. RESULTS:
      The three following categories emerged from the interview data: concerns about
      health, comments on the administration, and attitudes of professionalism. Nurses
      viewed the human swine influenza as a threat to their personal and families'
      health. However, nurses perceived that the severity of the disease was
      exaggerated by the public. Improvements in planning the circulation of
      information, allocation of manpower, and utilization of personal protective
      equipment were indicated. The emergency nurses demonstrated a sense of commitment
      and professional morale in promoting a high quality of nursing care. DISCUSSION:
      Various factors affecting the perceptions of emergency nurses toward their
      professional duties during the influenza pandemic were identified. By
      understanding these perceptions, appropriate planning, policies, and guidelines
      can be formulated to meet the healthcare needs of patients during future pandemic
      outbreaks.

PMID- 23142055
TI  - Human health risk from arsenical pesticide contaminated soils: a long-term
      greenhouse study.
AB  - Arsenic (As) bioaccessibility is an important factor in estimating human health
      risk. Bioaccessibility of As in soils is primarily dependent on As adsorption,
      which varies with residence time. This study evaluated the effect of soil aging
      on potential lifetime cancer risk associated with chronic exposure to As
      contaminated soils. Four soils, chosen based on their differences in As
      reactivity, were amended with two arsenical pesticides--sodium arsenate, and
      dimethylarsinic acid (DMA) at two rates (675 and 1500 mg kg(-1)). Rice was used
      as the test crop. Soil was sampled immediately after spiking, after 6 months, 1
      year, and 3 years. Bioaccessible and total soil As concentrations were used to
      calculate lifetime excess cancer risk (ECR), which decreased significantly with
      soil-pesticide equilibration time. Immokalee soil, with the least As adsorption
      capacity, showed the highest decrease in ECR after 6 months resulting in values
      lower than the USEPA's cancer risk range of 1 * 10(-4) to 1 * 10(-6). For all
      other soils, the ECR was much higher than the target range even after 3 years. In
      the absence of significant changes in As bioaccessibility with time, the total
      soil As concentration more directly influenced the changes in ECR values with
      soil aging.

PMID- 23142056
TI  - A ferrous oxalate mediated photo-Fenton system: toward an increased
      biodegradability of indigo dyed wastewaters.
AB  - This study assessed the applicability of a ferrous oxalate mediated photo-Fenton
      pretreatment for indigo-dyed wastewaters as to produce a biodegradable enough
      effluent, likely of being derived to conventional biological processes. The
      photochemical treatment was performed with ferrous oxalate and hydrogen peroxide
      in a Compound Parabolic Concentrator (CPC) under batch operation conditions. The
      reaction was studied at natural pH conditions (5-6) with indigo concentrations in
      the range of 6.67-33.33 mg L(-1), using a fixed oxalate-to-iron mass ratio
      (C(2)O(4)(2-)/Fe(2+)=35) and assessing the system's biodegradability at low (257
      mg L(-1)) and high (1280 mg L(-1)) H(2)O(2) concentrations. In order to seek the
      optimal conditions for the treatment of indigo dyed wastewaters, an experimental
      design consisting in a statistical surface response approach was carried out.
      This analysis revealed that the best removal efficiencies for Total Organic
      Carbon (TOC) were obtained for low peroxide doses. In general it was observed
      that after 20 kJ L(-1), almost every treated effluent increased its
      biodegradability from a BOD(5)/COD value of 0.4. This increase in the
      biodegradability was confirmed by the presence of short chain carboxylic acids as
      intermediate products and by the mineralization of organic nitrogen into nitrate.
      Finally, an overall decrease in the LC(50) for Artemia salina indicated a
      successful detoxification of the effluent.

PMID- 23142057
TI  - Voltammetric analysis with the use of a novel electro-polymerised graphene-nafion
      film modified glassy carbon electrode: simultaneous analysis of noxious
      nitroaniline isomers.
AB  - A new modified electrode was constructed by the electro-polymerization of 7-[(2,4
      dihydroxy-5-carboxybenzene)azo]-8-hydroxyquinoline-5-sulfonic acid (DHCBAQS) at a
      graphene-nafion modified glassy carbon electrode (GCE). The construction process
      was performed stepwise and at each step the electrochemical characteristics were
      investigated particularly with respect to the oxidation of the three noxious
      analytes, 2-nitroaniline (2-NA), 3-nitroaniline (3-NA), 4-nitroaniline (4-NA);
      the electrode treated with the fluorescence reagent DHCBAQS performed best. At
      this electrode, the differential pulse voltammetry peak currents of the three
      isomers increased linearly with their concentrations in the range of 0.05-0.60
      MUg mL(-1), respectively, and their corresponding limits of detection (LODs) were
      all about 0.022 MUg mL(-1). Furthermore, satisfactory results were obtained when
      this electrode was applied for the simultaneous quantitative analysis of the
      nitroaniline isomer mixtures by Principal component regression (PCR) and Partial
      least squares (PLS) as calibration methods (relative prediction error (PRE(T)) -
      9.04% and 9.23%) and average recoveries (101.0% and 101.7%), respectively. The
      above novel poly-DHCBAQS/graphene-nafion/GCE was successfully employed for the
      simultaneous analysis of the three noxious nitroaniline isomers in water and
      sewage samples.

PMID- 23142058
TI  - A distinct entity: the lesion looked like a wart but was, in fact, something far
      more unusual.

PMID- 23142059
TI  - Effect of abiraterone acetate and prednisone compared with placebo and prednisone
      on pain control and skeletal-related events in patients with metastatic
      castration-resistant prostate cancer: exploratory analysis of data from the COU
      AA-301 randomised trial.
AB  - BACKGROUND: Bone metastases are a major cause of morbidity in metastatic
      castration-resistant prostate cancer. Abiraterone acetate potently disrupts
      intracrine androgen receptor signalling pathways implicated in the progression of
      the disease, including bone metastases. We assessed data for pain control and
      skeletal-related events prospectively collected as part of the randomised, phase
      3 COU-AA-301 trial of abiraterone acetate plus prednisone versus placebo plus
      prednisone in patients with metastatic castration-resistant prostate cancer after
      docetaxel chemotherapy. METHODS: The COU-AA-301 trial enrolled patients with
      metastatic castration-resistant prostate cancer in whom one or two lines of
      chemotherapy (one docetaxel based) had been unsuccessful and who had Eastern
      Cooperative Oncology Group performance statuses of 2 or less. Pain intensity and
      interference of pain with daily activities were assessed with the Brief Pain
      Inventory-Short Form questionnaire at baseline, day 15 of cycle 1, and day 1 of
      each treatment cycle thereafter until discontinuation. We assessed, with
      prospectively defined response criteria that incorporated analgesic use,
      clinically meaningful changes in pain intensity and interference with daily
      living. We measured time to first occurrence of skeletal-related events, which we
      defined as pathological fracture, spinal cord compression, palliative radiation
      to bone, or bone surgery, and regularly assessed them throughout the study. Pain
      palliation was assessed in patients who had clinically significant baseline pain,
      whereas all other analyses were done in the overall intention-to-treat
      population. COU-AA-301 is registered with ClinicalTrials.gov, number NCT00638690.
      FINDINGS: Median follow-up was 20.2 months (IQR 18.4-22.1). In patients with
      clinically significant pain at baseline, abiraterone acetate and prednisone
      resulted in significantly more palliation (157 of 349 [45.0%] patients vs 47 of
      163 [28.8%]; p=0.0005) and faster palliation (median time to palliation 5.6
      months [95% CI 3.7-9.2] vs 13.7 months [5.4-not estimable]; p=0.0018) of pain
      intensity than did prednisone only. Palliation of pain interference (134 of 223
      [60.1%] vs 38 of 100 [38.0%], p=0.0002; median time to palliation of pain
      interference 1.0 months [95% CI 0.9-1.9] vs 3.7 months [2.7-not estimable],
      p=0.0004) and median duration of palliation of pain intensity (4.2 months [95% CI
      3.0-4.9] vs 2.1 months [1.4-3.7]; p=0.0056) were significantly better with
      abiraterone acetate and prednisone than with prednisone only. In the overall
      population, median time to occurrence of first skeletal-related event was
      significantly longer with abiraterone acetate and prednisone than with prednisone
      only (25.0 months [95% CI 25.0-not estimable] vs 20.3 months [16.9-not
      estimable]; p=0.0001). INTERPRETATION: In patients with metastatic castration
      resistant prostate cancer previously treated with docetaxel, abiraterone acetate
      and prednisone offer significant benefits compared with prednisone alone in terms
      of pain relief, delayed pain progression, and prevention of skeletal-related
      events. FUNDING: Janssen Research & Development and Janssen Global Services.

PMID- 23142060
TI  - Abiraterone acetate: a hat trick of clinical benefits.

PMID- 23142061
TI  - Virologic response and characterisation of HCV genotype 2-6 in patients receiving
      TMC435 monotherapy (study TMC435-C202).
AB  - BACKGROUND & AIMS: TMC435 is a potent, once-daily, investigational hepatitis C
      virus (HCV) NS3/4A protease inhibitor in phase III clinical development. In the
      phase II trial TMC435-C202 (NCT00812331), TMC435 displayed potent activity in
      genotype 4, 5 and 6 patients and in 3/6 genotype 2 patients, whereas no activity
      was observed with genotype 3. METHODS: Thirty-seven patients received TMC435
      monotherapy (200 mg once daily) for 7 days. HCV RNA, NS3 protease sequences and
      the corresponding phenotypes were evaluated. RESULTS: Genotype and isolate
      specific baseline polymorphisms at NS3 positions known to affect HCV protease
      inhibitor activity were present in all genotypes. Consistent with the antiviral
      activity observed in genotypes 4 and 6, TMC435 was active in vitro against all
      genotype 4 isolates, and against most genotype 6 polymorphisms when tested as
      single or double mutants. In contrast, in genotype 3 where no HCV RNA decline was
      observed, isolates displayed >700-fold increases in EC(50) attributed to the
      D168Q polymorphism. In genotypes 2 and 5, HCV RNA changes from baseline to Day 3
      ranged between -0.3 to -3.6 and -1.5 to -4.0 log(10)IU/ml, respectively, and
      isolates or site-directed mutants displayed intermediate in vitro susceptibility
      to TMC435 with fold changes in EC(50) between 15 and 78. Viral breakthrough in
      genotypes 4-6 was associated with emerging mutations including Q80R, R155K and/or
      D168E/V. CONCLUSIONS: Sequence and phenotypic analyses of baseline isolates
      identified polymorphisms which could explain the differences in antiviral
      activity between genotypes. Pathways of TMC435 resistance in genotypes 2-6 were
      similar to those identified in genotype 1.

PMID- 23142062
TI  - Non-alcoholic steatohepatitis: a non-invasive diagnosis by analysis of exhaled
      breath.
AB  - BACKGROUND & AIMS: Histological evaluation of a liver biopsy is the current gold
      standard to diagnose non-alcoholic steatohepatitis (NASH), but the procedure to
      obtain biopsies is associated with morbidity and high costs. Hence, only subjects
      at high risk are biopsied, leading to underestimation of NASH prevalence, and
      undertreatment. Since analysis of volatile organic compounds in breath has been
      shown to accurately identify subjects with other chronic inflammatory diseases,
      we investigated its potential as a non-invasive tool to diagnose NASH. METHODS:
      Wedge-shaped liver biopsies from 65 subjects (BMI 24.8-64.3 kg/m(2)) were
      obtained during surgery and histologically evaluated. The profile of volatile
      organic compounds in pre-operative breath samples was analyzed by gas
      chromatography-mass spectrometry and related to liver histology scores and plasma
      parameters of alanine aminotransferase (ALT) and aspartate aminotransferase
      (AST). RESULTS: Three exhaled compounds were sufficient to distinguish subjects
      with (n=39) and without NASH (n=26), with an area under the ROC curve of 0.77.
      The negative and positive predictive values were 82% and 81%. In contrast,
      elevated ALT levels or increased AST/ALT ratios both showed negative predictive
      values of 43%, and positive predictive values of 88% and 70%, respectively. The
      breath test reduced the hypothetical percentage of undiagnosed NASH patients from
      67-79% to 10%, and of misdiagnosed subjects from 49-51% to 18%. CONCLUSIONS:
      Analysis of volatile organic compounds in exhaled air is a promising method to
      indicate NASH presence and absence. In comparison to plasma transaminase levels,
      the breath test significantly reduced the percentage of missed NASH patients and
      the number of unnecessarily biopsied subjects.

PMID- 23142063
TI  - High serum level of fibroblast growth factor 21 is an independent predictor of
      non-alcoholic fatty liver disease: a 3-year prospective study in China.
AB  - BACKGROUND & AIMS: Fibroblast growth factor 21 (FGF21), a hormone predominantly
      secreted by the liver, has been shown to be positively associated with the
      severity of non-alcoholic fatty liver disease (NAFLD) in cross-sectional studies.
      We investigated the prospective association of FGF21 with NAFLD development in a
      3-year prospective study involving a population-based cohort comprising 808
      Chinese subjects. METHODS: Serum FGF21 levels at baseline and follow-up were
      measured using an enzyme-linked immunosorbent assay. Independent predictors of
      NAFLD development were identified using multiple logistic regressions. The
      predicting accuracy of the models was evaluated using area under the receiver
      operating characteristic (ROC) curves (AUCs). RESULTS: In subjects who had
      progressed to NAFLD, the baseline FGF21 concentration (319.12 pg/ml [172.65,
      518.78]) was significantly higher than that in subjects who did not develop NAFLD
      (199.10 pg/ml [123.56, 322.80]) (p <0.001). At follow-up, significant increase of
      FGF21 level was observed in those subjects who developed NAFLD (p <0.05).
      Baseline FGF21 was an independent predictor of NAFLD (OR: 7.102 [95% CI 2.488
      20.270]; p <0.001), together with body mass index (BMI) (OR: 1.489 [95% CI 1.310
      1.691]; p <0.001). The ROC-AUC was 0.816 (95% CI 0.766-0.867) for the FGF21
      Model, which was calculated with FGF21 and BMI. FGF21 Model <0.13 can be used to
      rule out (sensitivity=85.71%, negative likelihood ratio=0.23) and >=0.30 can be
      rule in (specificity=86.34%, positive likelihood ratio=3.66) ultrasonography
      diagnosed NAFLD after 3 years. CONCLUSIONS: High serum FGF21 concentration was an
      independent predictor of NAFLD in humans. The FGF21 Model and its cut-offs may be
      useful for early diagnosis and intervention of NAFLD.

PMID- 23142064
TI  - Psychoactive substances in seriously injured drivers in Denmark.
AB  - This study assesses the presence of a number of psychoactive substances,
      including alcohol, based on blood samples from 840 seriously injured drivers
      admitted to five selected hospitals located in five different regions of Denmark.
      The study was a part of the EU 6th framework program DRUID (Driving Under the
      Influence of Drugs, Alcohol and Medicines). Blood samples were screened for 30
      illegal and legal psychoactive substances and metabolites as well as ethanol.
      Danish legal limits were used to evaluate the frequency of drivers violating the
      Danish legislation while limit of quantification (LOQ) was used for monitoring
      positive drivers. Tramadol is not included in the Danish legislation therefore
      the general cut off, as decided in the DRUID project was used. Overall, ethanol
      (18%) was the most frequently identified compound (alone or in combination with
      other drugs) exceeding the legal limit, which is 0.53g/l in Denmark. The
      percentage of seriously injured drivers testing positive for medicinal drugs at
      levels above the Danish legal limit was 6.8%. Benzodiazepines and Z-drugs (6.4%)
      comprised the majority of this group. One or more illegal drugs (primarily
      amphetamines and cannabis) were found to be above the Danish legal limit in 4.9%
      of injured drivers. Young men (median age 31 years) were over-represented among
      injured drivers who violated Danish law for alcohol and drugs. Diazepam (4.4%),
      tramadol (3.2%), and clonazepam (3.0%) were the medicinal drugs most frequently
      detected at levels above LOQ, whereas amphetamines (5.4%) (amphetamine [5.2%] and
      methamphetamine [1.5%]), tetrahydrocannabinol (3.7%), and cocaine (3.3%),
      including the metabolite benzoylecgonine, were the most frequently detected
      illegal drugs. A driver could be positive for more than one substance; therefore,
      percentages are not mutually exclusive. Poly-drug use was observed in 112 (13%)
      seriously injured drivers. Tramadol was detected above DRUID cutoffs in 2.1% of
      seriously injured drivers. This is 3.5 times that observed in a Danish survey of
      randomly selected drivers. Moreover, illegal and medicinal drug levels above the
      Danish legal limit were present more than 10 times as frequently as in injured
      drivers, whereas ethanol was present more than 30 times as frequently than in
      randomly selected drivers. The results indicate that there is an increased risk
      in traffic when driving under the influence of psychoactive drugs, especially
      alcohol in young male drivers.

PMID- 23142065
TI  - Poststroke fatigue is associated with caudate infarcts.
AB  - OBJECTIVE: The caudate nucleus may be involved in the pathogenesis of the fatigue
      observed in neurological disorders. However, the significance of caudate lesions
      in poststroke fatigue (PSF) is unknown. This study examined the association
      between caudate infarcts and PSF. METHODS: Five hundred Chinese patients with
      acute ischemic stroke admitted to the acute stroke unit of a university
      affiliated regional hospital in Hong Kong participated in the study. All
      participants were assessed for PSF with the Fatigue Severity Scale (FSS) three
      months after their index stroke. PSF was defined as a mean FSS score of 4.0 or
      more. Physical functioning and depressive symptoms were measured by the Barthel
      Index (BI) and the Geriatric Depression Scale (GDS). RESULTS: One hundred and
      twenty-five (25.0%) of the patients had PSF. Compared to the non-fatigue group,
      the PSF patients were more likely to be women and had hyperlipidemia, lower BI
      and higher GDS scores. Caudate (8.0% versus 1.3%, p=0.001) and putamen (19.2%
      versus 12.0%, p=0.043) acute infarcts were more common in the PSF group, whereas
      pons infarcts (13.6% versus 22.2%, p=0.038) were less common. Acute caudate
      infarcts remained an independent predictor of PSF in the multivariate analysis,
      with an odds ratio of 6.4. CONCLUSIONS: The results suggest that patients with
      PSF are more likely to have caudate infarcts.

PMID- 23142066
TI  - Design, synthesis and in vitro anti-proliferative activity of 4,6
      quinazolinediamines as potent EGFR-TK inhibitors.
AB  - 4-Anilino-6-substituted-quinazolines were designed, synthesized and evaluated for
      EGFR-TK and tumor growth inhibitory activities. The target compounds were
      designed with enamine ester or urea moieties appended at the C-6 of quinazoline
      as additional hydrogen bond acceptor functions. Most of the synthesized compounds
      displayed potent EGFR-TK inhibitory activity at 10 MUM and the 6-ureido
      anilinoquinazoline derivative 7a showed IC50 value of 0.061 MUM. Moreover, six
      compounds were tested by National Cancer Institute (NCI), USA for their anti
      proliferative activity at 10 MUM in full NCI 60 cell panel. Compound 7a was
      further assayed for five dose molar ranges in full NCI 60 cell panel and
      exhibited remarkable growth inhibitory activity pattern against Non-Small Cell
      Lung Cancer EKVX (GI50 = 0.37 MUM), NCI-H322M (GI50 = 0.36 MUM), Renal Cancer
      A498 (GI50 = 0.46 MUM), TK-10 (GI50 = 0.99 MUM) and Breast Cancer MDA-MB-468
      (GI50 = 1.096 MUM) which are of high EGFR expression. Docking study was performed
      for the active compounds into ATP binding site of EGFR-TK which showed similar
      binding mode to gefitinib and additional binding with Cys-773 at the gatekeeper
      of EGFR-TK enzyme.

PMID- 23142067
TI  - Identification of reproducible individualized targets for treatment of depression
      with TMS based on intrinsic connectivity.
AB  - Transcranial magnetic stimulation (TMS) to the left dorsolateral prefrontal
      cortex (DLPFC) is used clinically for the treatment of depression however
      outcomes vary greatly between patients. We have shown that average clinical
      efficacy of different left DLPFC TMS sites is related to intrinsic functional
      connectivity with remote regions including the subgenual cingulate and suggested
      that functional connectivity with these remote regions might be used to identify
      optimized left DLPFC targets for TMS. However it remains unclear if and how this
      connectivity-based targeting approach should be applied at the single-subject
      level to potentially individualize therapy to specific patients. In this article
      we show that individual differences in DLPFC connectivity are large, reproducible
      across sessions, and can be used to generate individualized DLPFC TMS targets
      that may prove clinically superior to those selected on the basis of group
      average connectivity. Factors likely to improve individualized targeting
      including the use of seed maps and the focality of stimulation are investigated
      and discussed. The techniques presented here may be applicable to individualized
      targeting of focal brain stimulation across a range of diseases and stimulation
      modalities and can be experimentally tested in clinical trials. 

PMID- 23142068
TI  - Genetic effects on behavior are mediated by neurotransmitters and large-scale
      neural networks.
AB  - Claims of gene-behavior associations are complex and sometimes difficult to
      replicate because these relationships involve many downstream endogenous and
      environmental processes that mediate genetic effects. Knowing these mediating
      processes is critical to understanding the links between genes and behavior and
      how these factors differ between people. We identified and characterized the
      effects of a gene on neurochemistry and neural networks to elucidate the
      mechanism, at the systems level, whereby genes influence cognition. Catechol-O
      methyltransferase (COMT) degrades dopamine in the prefrontal cortex (PFC) and is
      polymorphic with alleles differing in enzymatic activity. We found that COMT
      genotype determined dopamine synthesis, such that individuals with greater COMT
      activity synthesized more dopamine. Dopamine synthesis in the midbrain and
      ventral striatum affected functional connectivity in the default mode network,
      likely through the mesocorticolimbic pathway, in an inverted-U pattern with
      greater functional connectivity in medial PFC associated with intermediate levels
      of COMT activity and dopamine. Greater functional connectivity correlated with
      greater deactivation during performance of a set-shifting task that engaged the
      PFC. Greater deactivation was in turn associated with better performance. The
      integration of these results yields a model whereby COMT affects prefrontal
      function by a mechanism involving dopaminergic modulation of the default mode
      network. The model features the well-known inverted-U function between dopamine
      and performance and supports the hypothesis that dopamine and the default mode
      network shift attentional resources to influence prefrontal cognition. 

PMID- 23142069
TI  - Comparison of 2D and 3D single-shot ASL perfusion fMRI sequences.
AB  - Arterial spin labeling (ASL) can be implemented by combining different labeling
      schemes and readout sequences. In this study, the performance of 2D and 3D single
      shot pulsed-continuous ASL (pCASL) sequences was assessed in a group of young
      healthy volunteers undergoing a baseline perfusion and a functional study with a
      sensory-motor activation paradigm. The evaluated sequences were 2D echo-planar
      imaging (2D EPI), 3D single-shot fast spin-echo with in-plane spiral readout (3D
      FSE spiral), and 3D single-shot gradient-and-spin-echo (3D GRASE). The 3D
      sequences were implemented with and without the addition of an optimized
      background suppression (BS) scheme. Labeling efficiency, signal-to-noise ratio
      (SNR), and gray matter (GM) to white matter (WM) contrast ratio were assessed in
      baseline perfusion measurements. 3D acquisitions without BS yielded 2-fold
      increments in spatial SNR, but no change in temporal SNR. The addition of BS to
      the 3D sequences yielded a 3-fold temporal SNR increase compared to the
      unsuppressed sequences. 2D EPI provided better GM-to-WM contrast ratio than the
      3D sequences. The analysis of functional data at the subject level showed a 3
      fold increase in statistical power for the BS 3D sequences, although the
      improvement was attenuated at the group level. 3D without BS did not increase the
      maximum t-values, however, it yielded larger activation clusters than 2D. These
      results demonstrate that BS 3D single-shot imaging sequences improve the
      performance of pCASL in baseline and activation studies, particularly for
      individual subject analyses where the improvement in temporal SNR translates into
      markedly enhanced power for task activation detection. 

PMID- 23142070
TI  - Priming of visual cortex by temporal attention? The effects of temporal
      predictability on stimulus(-specific) processing in early visual cortical areas.
AB  - In recent studies it has been shown that temporal predictability of expected
      events alters processing in perception and action. Yet, the neural mechanism(s)
      by which temporal predictability biases this processing is to date little
      understood. Therefore, in the present fMRI study we investigated how temporal
      predictability affects neural processing in visual cortical areas. For this,
      thirty-four participants either categorized the gender or the movement direction
      of vertically or horizontally moving faces in different blocks of trials.
      Temporal predictability of stimulus onset was manipulated by the presence or
      absence of an auditory alerting signal validly predicting stimulus onset. The
      behavioral data revealed a clear performance benefit for the presence of an
      alerting signal. Neuroimaging results showed that irrespective of the currently
      performed task temporal predictability significantly reduced activation in the
      primary visual cortex. This activation reduction correlated with the alerting
      signal-related performance benefit. Furthermore, we did not find a selective
      influence of increased temporal predictability on target-specific visual
      processing (faces or movement) in the respective material-specific visual brain
      areas. Together, these findings suggest an increased task-unspecific readiness by
      the alerting signal that might result in more efficient transmission of stimulus
      codes into response codes. 

PMID- 23142072
TI  - Role of kruppel-like transcription factors in adipogenesis.
AB  - The zinc-finger transcription factors of the kruppel-like factor family (KLF) are
      critical in many physiological and pathological processes including cell
      proliferation, differentiation, inflammation, and apoptosis. Recently, there is
      increasing evidence that suggests these KLFs have an important role in fat
      biology. This review summarizes the role of KLFs in lipid metabolism, especially
      in adipogenesis, and reveals the relationship networks among members of KLF
      family in differentiation.

PMID- 23142071
TI  - Dissimilar processing of emotional facial expressions in human and monkey
      temporal cortex.
AB  - Emotional facial expressions play an important role in social communication
      across primates. Despite major progress made in our understanding of categorical
      information processing such as for objects and faces, little is known, however,
      about how the primate brain evolved to process emotional cues. In this study, we
      used functional magnetic resonance imaging (fMRI) to compare the processing of
      emotional facial expressions between monkeys and humans. We used a 2*2*2
      factorial design with species (human and monkey), expression (fear and chewing)
      and configuration (intact versus scrambled) as factors. At the whole brain level,
      neural responses to conspecific emotional expressions were anatomically confined
      to the superior temporal sulcus (STS) in humans. Within the human STS, we found
      functional subdivisions with a face-selective right posterior STS area that also
      responded to emotional expressions of other species and a more anterior area in
      the right middle STS that responded specifically to human emotions. Hence, we
      argue that the latter region does not show a mere emotion-dependent modulation of
      activity but is primarily driven by human emotional facial expressions.
      Conversely, in monkeys, emotional responses appeared in earlier visual cortex and
      outside face-selective regions in inferior temporal cortex that responded also to
      multiple visual categories. Within monkey IT, we also found areas that were more
      responsive to conspecific than to non-conspecific emotional expressions but these
      responses were not as specific as in human middle STS. Overall, our results
      indicate that human STS may have developed unique properties to deal with social
      cues such as emotional expressions. 

PMID- 23142073
TI  - First report of the use of a saxitoxin-protein conjugate to develop a DNA aptamer
      to a small molecule toxin.
AB  - Saxitoxin (STX) is a low molecular weight neurotoxin mainly produced by certain
      marine dinoflagellates that, along with its family of similarly related paralytic
      shellfish toxins, may cause the potentially fatal intoxication known as paralytic
      shellfish poisoning. Illness and fatality rates are low due to the effective
      monitoring programs that determine when toxins exceed the established regulatory
      action level and effectuate shellfish harvesting closures accordingly. Such
      monitoring programs rely on the ability to rapidly screen large volumes of
      samples. Many of the screening assays currently available employ antibodies or
      live animals. This research focused on developing an analytical recognition
      element that would eliminate the challenges associated with the limited
      availability of antibodies and the use of animals. Here we report the discovery
      of a DNA aptamer that targets STX. Concentration-dependent and selective binding
      of the aptamer to STX was determined using a surface plasmon resonance sensor.
      Not only does this work represent the first reported aptamer to STX, but also the
      first aptamer to any marine biotoxin. A novel strategy of using a toxin-protein
      conjugate for DNA aptamer selection was successfully implemented to overcome the
      challenges associated with aptamer selection to small molecules. Taking advantage
      of such an approach could lead to increased diversity and accessibility of
      aptamers to low molecular weight toxins, which could then be incorporated as
      analytical recognition elements in diagnostic assays for foodborne toxin
      detection. The selected STX aptamer sequence is provided here, making it
      available to any investigator for use in assay development for the detection of
      STX.

PMID- 23142074
TI  - Clinicopathologic features of brain metastases from gynecologic malignancies: a
      retrospective study of 139 cases (KCOG-G1001s trial).
AB  - OBJECTIVE: Although brain metastases from gynecologic malignancies are rare, such
      cases have been gradually increasing in number. The aim of the present study was
      to evaluate the clinicopathologic features and prognostic factors of brain
      metastases from gynecologic malignancies. METHODS: Retrospective analysis of 139
      patients with brain metastases from gynecologic malignancies was carried out as a
      multi-institutional study. The clinicophathological data of the patients were
      collected from medical records. RESULTS: Median survival time of the patients
      with brain metastases was 12.5 months for the ovarian cancer group, 6.2 months
      for the corpus cancer group, and 5.0 months for the cervical cancer group; two
      year overall survival rates were 19.7%, 6.1%, and 4.8%, respectively.
      Multivariate analysis revealed ovarian/tubal/peritoneal origin, KPS >70, single
      brain metastasis, absence of extracranial disease, cranial surgery, cranial
      radiotherapy, and chemotherapy to be independent favorable prognostic factors
      associated with overall survival. CONCLUSION: It is considered that aggressive
      multimodal therapy is warranted in the treatment of brain metastases from
      gynecologic malignancies in carefully selected patients. The present study may
      provide a platform for the discussion of management strategies in these rare
      clinical scenarios.

PMID- 23142075
TI  - The prognostic value of vascular endothelial growth factor in ovarian cancer: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: The prognostic role of vascular endothelial growth factor (VEGF) in
      ovarian cancer remains inconclusive. This meta-analysis aimed to explore the
      association between VEGF overexpression and survival outcomes in ovarian cancer
      patients. METHODS: Studies were identified from PubMed and EMBASE searches
      performed on January 2nd, 2011. After careful review, survival data were
      extracted from eligible studies. A meta-analysis was performed to generate
      combined hazard ratio (HR) for progression-free survival (PFS) and overall
      survival (OS) in serum and tumor tissue studies. RESULTS: Sixteen studies with
      1111 patients were analyzed. Elevated serum VEGF was significantly associated
      with poor PFS [HR 2.46, 95% CI (1.84, 3.29)] and OS [HR 2.21, 95% CI (1.57,
      3.13)]. No significant heterogeneity existed in serum studies. Similarly, tissue
      VEGF overexpression was associated with poor PFS [HR 1.63, 95% CI (1.09, 2.42)]
      and OS [HR 1.70, 95% CI (1.01, 2.87)]. However, significant heterogeneity was
      found in tissue studies, with I(2) of 44% for PFS and 64% for OS. Studies were
      stratified into subgroups by International Federation of Gynecology and
      Obstetrics (FIGO) stages. Subgroup analyses showed that high tissue VEGF was
      significantly associated with shorter PFS [HR 5.34, 95% CI (1.95, 14.59)] and OS
      [HR 6.13, 95% CI (2.47, 15.26)] in studies where predominantly early-stage
      patients were included, but not in studies with a majority of advanced-stage
      patients. Subgroup analysis was not performed in serum studies because all those
      studies enrolled more patients in advanced stages than early stages. CONCLUSIONS:
      Overexpression of VEGF in primary tumor and serum associates with poor PFS and OS
      for patients with ovarian cancer. The association between high tissue VEGF level
      and poor prognosis exists in early stage patients, but not in advanced stage
      patients.

PMID- 23142076
TI  - Is perioperative visual estimation of intra-abdominal tumor spread reliable in
      ovarian cancer surgery after neoadjuvant chemotherapy?
AB  - OBJECTIVE: Most cases of epithelial ovarian cancer (EOC) are diagnosed in an
      advanced stage. When the disease has spread intra-abdominally, complete surgical
      tumor debulking is the single most important prognostic factor. Neoadjuvant
      chemotherapy (NACT) before surgery can cause fibrosis and adhesions in the
      peritoneal cavity and may interfere with the perioperative evaluation of tumor
      spread. In this prospective study, we evaluated whether perioperative visual
      assessment of tumor dissemination is similar in patients undergoing primary and
      interval surgery for EOC. METHODS: Systematic visual evaluation of tumor spread
      was performed at the start of primary surgery/diagnostic laparoscopy (n=39) or
      interval surgery (n=16). Peritoneal cavity was divided into 22 anatomical
      regions. The carefully documented results of the visual assessment were compared
      with the histopathological analysis of 220 biopsies from primary and 92 biopsies
      from interval surgery. RESULTS: In primary surgery, perioperative visual
      estimation of tumor spread showed 98% sensitivity, 76% specificity and 95%
      accuracy compared to histopathology. The corresponding figures after NACT were
      86%, 76% and 84%, respectively. The difference in sensitivity and accuracy in
      primary and interval operations was statistically significant (p<0.001).
      CONCLUSIONS: In advanced EOC, microscopically carcinomatous areas have a benign
      visual appearance more often after NACT than at primary surgery. NACT may
      interfere with the perioperative visual evaluation of tumor spread and thus lead
      to incomplete resection of tumor in potentially resectable areas.

PMID- 23142077
TI  - TRAF2 Sets a threshold for extrinsic apoptosis by tagging caspase-8 with a
      ubiquitin shutoff timer.
AB  - Apoptotic caspase activation mechanisms are well defined, yet inactivation modes
      remain unclear. The death receptors (DRs), DR4, DR5, and Fas, transduce cell
      extrinsic apoptotic signals by recruiting caspase-8 into a death-inducing
      signaling complex (DISC). At the DISC, Cullin3-dependent polyubiquitination on
      the small catalytic subunit of caspase-8 augments stimulation. Here we report
      that tumor necrosis factor receptor-associated factor 2 (TRAF2) interacts with
      caspase-8 at the DISC, downstream of Cullin3. TRAF2 directly mediates RING
      dependent, K48-linked polyubiquitination on the large catalytic domain of caspase
      8. This modification destines activated caspase-8 molecules to rapid proteasomal
      degradation upon autoprocessing and cytoplasmic translocation. TRAF2 depletion
      lowers the signal threshold for DR-mediated apoptosis, altering cell life versus
      death decisions in vitro and in vivo. Thus, TRAF2 sets a critical barrier for
      cell-extrinsic apoptosis commitment by tagging activated caspase-8 with a K48
      ubiquitin shutoff timer. These results may have important implications for
      caspase regulation mechanisms.

PMID- 23142078
TI  - Metabolic stress controls mTORC1 lysosomal localization and dimerization by
      regulating the TTT-RUVBL1/2 complex.
AB  - The metabolism of glucose and glutamine, primary carbon sources utilized by
      mitochondria to generate energy and macromolecules for cell growth, is directly
      regulated by mTORC1. We show that glucose and glutamine, by supplying carbons to
      the TCA cycle to produce ATP, positively feed back to mTORC1 through an AMPK-,
      TSC1/2-, and Rag-independent mechanism by regulating mTORC1 assembly and its
      lysosomal localization. We discovered that the ATP-dependent TTT-RUVBL1/2 complex
      was disassembled and repressed by energy depletion, resulting in its decreased
      interaction with mTOR. The TTT-RUVBL complex was necessary for the interaction
      between mTORC1 and Rag and formation of mTORC1 obligate dimers. In cancer
      tissues, TTT-RUVBL complex mRNAs were elevated and positively correlated with
      transcripts encoding proteins of anabolic metabolism and mitochondrial function
      all mTORC1-regulated processes. Thus, the TTT-RUVBL1/2 complex responds to the
      cell's metabolic state, directly regulating the functional assembly of mTORC1 and
      indirectly controlling the nutrient signal from Rags to mTORC1.

PMID- 23142079
TI  - The deacetylase Sirt6 activates the acetyltransferase GCN5 and suppresses hepatic
      gluconeogenesis.
AB  - Hepatic glucose production (HGP) maintains blood glucose levels during fasting
      but can also exacerbate diabetic hyperglycemia. HGP is dynamically controlled by
      a signaling/transcriptional network that regulates the expression/activity of
      gluconeogenic enzymes. A key mediator of gluconeogenic gene transcription is PGC
      1alpha. PGC-1alpha's activation of gluconeogenic gene expression is dependent
      upon its acetylation state, which is controlled by the acetyltransferase GCN5 and
      the deacetylase Sirt1. Nevertheless, whether other chromatin modifiers
      particularly other sirtuins-can modulate PGC-1alpha acetylation is currently
      unknown. Herein, we report that Sirt6 strongly controls PGC-1alpha acetylation.
      Surprisingly, Sirt6 induces PGC-1alpha acetylation and suppresses HGP. Sirt6
      depletion decreases PGC-1alpha acetylation and promotes HGP. These acetylation
      effects are GCN5 dependent: Sirt6 interacts with and modifies GCN5, enhancing
      GCN5's activity. Lepr(db/db) mice, an obese/diabetic animal model, exhibit
      reduced Sirt6 levels; ectopic re-expression suppresses gluconeogenic genes and
      normalizes glycemia. Activation of hepatic Sirt6 may therefore be therapeutically
      useful for treating insulin-resistant diabetes.

PMID- 23142080
TI  - Transcriptome-wide miR-155 binding map reveals widespread noncanonical microRNA
      targeting.
AB  - MicroRNAs (miRNAs) are essential components of gene regulation, but
      identification of miRNA targets remains a major challenge. Most target prediction
      and discovery relies on perfect complementarity of the miRNA seed to the 3'
      untranslated region (UTR). However, it is unclear to what extent miRNAs target
      sites without seed matches. Here, we performed a transcriptome-wide
      identification of the endogenous targets of a single miRNA-miR-155-in a
      genetically controlled manner. We found that approximately 40% of miR-155
      dependent Argonaute binding occurs at sites without perfect seed matches. The
      majority of these noncanonical sites feature extensive complementarity to the
      miRNA seed with one mismatch. These noncanonical sites confer regulation of gene
      expression, albeit less potently than canonical sites. Thus, noncanonical miRNA
      binding sites are widespread, often contain seed-like motifs, and can regulate
      gene expression, generating a continuum of targeting and regulation.

PMID- 23142081
TI  - mTOR complex 2 regulates proper turnover of insulin receptor substrate-1 via the
      ubiquitin ligase subunit Fbw8.
AB  - The mammalian target of rapamycin (mTOR) integrates signals from nutrients and
      insulin via two distinct complexes, mTORC1 and mTORC2. Disruption of mTORC2
      impairs the insulin-induced activation of Akt, an mTORC2 substrate. Here, we
      found that mTORC2 can also regulate insulin signaling at the level of insulin
      receptor substrate-1 (IRS-1). Despite phosphorylation at the mTORC1-mediated
      serine sites, which supposedly triggers IRS-1 downregulation, inactive IRS-1
      accumulated in mTORC2-disrupted cells. Defective IRS-1 degradation was due to
      attenuated expression and phosphorylation of the ubiquitin ligase substrate
      targeting subunit, Fbw8. mTORC2 stabilizes Fbw8 by phosphorylation at Ser86,
      allowing the insulin-induced translocation of Fbw8 to the cytosol where it
      mediates IRS-1 degradation. Thus, mTORC2 negatively feeds back to IRS-1 via
      control of Fbw8 stability and localization. Our findings reveal that in addition
      to persistent mTORC1 signaling, heightened mTORC2 signals can promote insulin
      resistance due to mTORC2-mediated degradation of IRS-1.

PMID- 23142082
TI  - In vitro transcription activities of Pol IV, Pol V, and RDR2 reveal coupling of
      Pol IV and RDR2 for dsRNA synthesis in plant RNA silencing.
AB  - In Arabidopsis, RNA-dependent DNA methylation and transcriptional silencing
      involves three nuclear RNA polymerases that are biochemically undefined: the
      presumptive DNA-dependent RNA polymerases Pol IV and Pol V and the putative RNA
      dependent RNA polymerase RDR2. Here we demonstrate their RNA polymerase
      activities in vitro. Unlike Pol II, Pols IV and V require an RNA primer, are
      insensitive to alpha-amanitin, and differ in their ability to displace the
      nontemplate DNA strand during transcription. Biogenesis of 24 nt small
      interfering RNAs (siRNAs), which guide cytosine methylation to corresponding
      sequences, requires both Pol IV and RDR2, which physically associate in vivo.
      Whereas Pol IV does not require RDR2 for activity, RDR2 is nonfunctional in the
      absence of associated Pol IV. These results suggest that the physical and
      mechanistic coupling of Pol IV and RDR2 results in the channeled synthesis of
      double-stranded precursors for 24 nt siRNA biogenesis.

PMID- 23142083
TI  - Large scale preparation of midkine antisense oligonucleotides nanoliposomes by a
      cross-flow injection technique combined with ultrafiltration and high-pressure
      extrusion procedures.
AB  - The midkine antisense oligonucleotide (MK-ASODN, 5'-CCC CGG GCC GCC CTT CTT CA
      3') nanoliposomes have been identified to suppress hepatocellular carcinoma (HCC)
      growth effectively, and have a great potential to be an effective target drug for
      HCC. In this study, a facile and reproducible method for large-scale preparation
      of MK-ASODN nanoliposomes followed by lyophilization has been developed
      successfully. Meanwhile, the MK-ASODN nanoliposomes characteristics, storage
      stability and their antitumor efficiency were studied. The mean particle size of
      MK-ASODN nanoliposomes were 229.43+/-15.11 nm, and the zeta potential were 29.7+/
      1.1 mV. High entrapment efficiency values were achieved around 90%. Transmission
      electron microscopy images revealed spherical shaped nanoliposomes. Nanoliposomes
      allowed sustained MK-ASODN release for as long as 14 days. During 180 days of
      storage, freeze-dried nanoliposomes showed no significant change in the mean
      size, zeta potential, entrapment efficiency and drug release ratio. Regarding
      their antitumor efficiency, the in vitro proliferation of human liver cancer
      cells were significantly inhibited by the MK-ASODN nanoliposomes. Furthermore,
      the MK-ASOND nanoliposomes also significantly inhibited the growth of HCC in the
      mouse model. In summary, the results confirmed that this large-scale preparation
      of MK-ASOND nanoliposomes was facile and reproducible, and potentially, could
      speed up the application process of our MK-ASOND nanoliposomes for HCC therapy.

PMID- 23142084
TI  - Prednisolone and cyclosporine A: effects on an experimental model of
      ancylostomiasis.
AB  - Corticosteroids and cyclosporine A (CsA) are important clinical immunosuppressive
      drugs used in the maintenance of organ transplants and in suppressing undesired
      autoimmune or allergic immune responses. To study the effect of CsA and
      prednisolone on the course of an Ancylostoma ceylanicum infection, hamsters were
      treated with commercially available prednisolone or CsA. For both drugs, half the
      recommended dose was sufficient to inhibit the proliferation of more than 70% of
      hamster lymph node cells. There was no difference in the recovery of adult worms;
      however, animals treated with prednisolone presented with low egg counts in the
      feces. Infection with A. ceylanicum resulted in an increase in specific
      antibodies against adult worm antigens, but hamsters treated with either drug
      presented with lower IgG titers. We observed that A. ceylanicum infection caused
      peripheral cellular immune suppression, which is characterized by a reduction in
      the total white cell count, neutropenia and lymphopenia. We also observed a
      lymphoplasmacytic pattern and few eosinophils in the mucosal inflammatory
      infiltrate for all the animals. The animals treated with prednisolone showed
      changes in the architecture of the intestine, including the loss of the mucosa,
      intense congestion and inflammation. In spleen, we observed hyperplasia of white
      pulp in all infected animals; in addition, there was a loss of tissue
      architecture in the animals treated with prednisolone. In conclusion, this work
      shows that an A. ceylanicum infection leads to acute peripheral cellular immune
      suppression in hamsters but not humoral immune suppression and that CsA treatment
      does not interfere with the process of infection. However, prednisolone treatment
      causes intestinal injury, what could hamper the parasite attachment to the
      intestinal wall, and as a result affects copulation and, consequently, decreases
      the number of eggs eliminated in the feces. Moreover, the possibility that the
      drug can also be exerting an effect on female fertility should be considered.

PMID- 23142085
TI  - Anti-anaerobic potential of ranbezolid: insight into its mechanism of action
      against Bacteroides fragilis.
AB  - This study reports the anti-anaerobic properties of ranbezolid, a new
      investigational oxazolidinone. A time-kill kinetics study against anaerobes
      showed that ranbezolid was superior to linezolid and killed the anaerobic
      pathogens at 4-8h, except for Bacteroides fragilis where killing was observed at
      24h. In addition, the time-kill kinetics study showed a concentration-dependent
      bactericidal potential of ranbezolid against anaerobes. Ranbezolid showed
      5.39log(10) reduction and linezolid showed 1.15log(10) reduction in murine disk
      implant infection with B. fragilis ATCC 25285. Ranbezolid was very potent and
      showed fast protein synthesis inhibition against B. fragilis, a Gram-negative
      anaerobe. In addition, non-specific cell wall synthesis inhibition was also
      observed with ranbezolid. The potent and fast protein synthesis inhibition along
      with an additional mode of action of cell wall synthesis inhibition could be
      responsible for the cidal effect of ranbezolid against Gram-negative anaerobes.

PMID- 23142086
TI  - Novel DNA gyrase inhibitors: microbiological characterisation of pyrrolamides.
AB  - Pyrrolamides are a novel class of antibacterial agents that target DNA gyrase,
      resulting in inhibition of DNA synthesis and bacterial cell death. In these
      studies, advanced compounds were shown to have potent in vitro activity against
      selected Gram-positive and Gram-negative pathogens, including meticillin
      resistant Staphylococcus aureus, meticillin- and quinolone-resistant S. aureus,
      vancomycin-resistant enterococci, penicillin-resistant Streptococcus pneumoniae
      and beta-lactamase-producing Haemophilus influenzae and Moraxella catarrhalis.
      Representatives of the class were demonstrated to be bactericidal, with
      frequencies of spontaneous resistance <=1*10(-7) when plated at concentrations
      equivalent to their minimum inhibitory concentration. Mode of action studies
      suggested that the activity of these compounds is due to inhibition of the GyrB
      subunit of DNA gyrase in key pathogens. The antibacterial activity, spectrum and
      mode of action of these compounds underscore the promise of the pyrrolamide
      series as attractive candidates for the treatment of several clinical
      indications, including respiratory and soft tissue infections.

PMID- 23142087
TI  - Underlying mechanisms of carbapenem resistance in extended-spectrum beta
      lactamase-producing Klebsiella pneumoniae and Escherichia coli isolates at a
      tertiary care centre in Lebanon: role of OXA-48 and NDM-1 carbapenemases.
AB  - A recent increase in carbapenem resistance among extended-spectrum beta-lactamase
      (ESBL)-producing Klebsiella pneumoniae and Escherichia coli isolates at a major
      tertiary care centre in Lebanon prompted the initiation of this study.
      Consecutive ESBL-producing isolates were tested for resistance to carbapenems,
      with initial screening by disk diffusion and Etest using ertapenem. The modified
      Hodge test was also performed. PCR of beta-lactamase-encoding genes, including
      bla(NDM-1), bla(KPC), bla(OXA-48), bla(CTX-M), bla(TEM), bla(SHV), bla(CMY-2) and
      bla(OXA-1), as well as outer membrane porin genes (ompC and ompF) was performed.
      Sequencing, efflux pump inhibitor tests and random amplified polymorphic DNA
      (RAPD) analysis were performed. In total, 14 (2.45%) of 572 K. pneumoniae and 24
      (1.07%) of 2243 E. coli were ertapenem-non-susceptible [minimum inhibitory
      concentration (MIC) >=0.25 MUg/mL]. Resistance to other carbapenems was variable.
      PCR and sequencing analysis revealed that isolates harboured different beta
      lactamase genes, including bla(OXA-1), bla(CTX-M-15), bla(TEM-1), bla(CMY-2),
      bla(OXA-48) and bla(NDM-1). In addition, K. pneumoniae lacked the outer membrane
      porin-encoding genes, whilst E. coli harboured them with detected mutations. CTX
      M-15 was carried on a 90 kb plasmid, whilst OXA-48 was carried on a 70 kb
      plasmid. Efflux pump inhibition significantly decreased MICs in E. coli. RAPD
      analysis demonstrated genomic variability. In conclusion, carbapenem resistance
      in ESBL-producing K. pneumoniae and E. coli is due to the combined effect of beta
      lactamases with porin impermeability and/or efflux pump activity observed in
      these organisms, and in a number of isolates is due to the production of the
      carbapenemase-encoding genes bla(OXA-48) and the newly emerging bla(NDM-1).

PMID- 23142088
TI  - Bmdelta phenotype implies involvement of Notch signaling in body segmentation and
      appendage development of silkworm, Bombyx mori.
AB  - The domesticated silkworm, Bombyx mori, belongs to the intermediate germband
      insects, in which the anterior segments are specified in the blastoderm, while
      the remaining posterior segments are sequentially generated from the cellularized
      growth zone. The pattern formation is distinct from Drosophila but somewhat
      resembles a vertebrate. Notch signaling is involved in the segmentation of
      vertebrates and spiders. Here, we studied the function of Notch signaling in
      silkworm embryogenesis via RNA interference (RNAi). Depletion of Bmdelta, the
      homolog of the Notch signaling ligand, led to severe defects in segment
      patterning, including a loss of posterior segments and irregular segment
      boundaries. The paired appendages on each segment were symmetrically fused along
      the ventral midline in Bmdelta RNAi embryos. An individual segment seemed to
      possess only one segmental appendage. Segmentation in prolegs could be observed.
      Our results show that Notch signaling is employed in not only appendage
      development but also body segmentation. Thus, conservation of Notch-mediated
      segmentation could also be extended to holometabolous insects. The involvement of
      Notch signaling seems to be the ancestral segmentation mechanism of arthropods.

PMID- 23142089
TI  - Comparing the secretory pathway in honeybee venom and hypopharyngeal glands.
AB  - We provide insights into the secretory pathway of arthropod gland systems by
      comparing the royal jelly-producing hypopharyngeal glands and the venom-producing
      glands of the honeybee, Apis mellifera. These glands have different functions and
      different product release characteristics, but both belong to the class 3 types
      of insect glands, each being composed of two cells, a secretory cell and a
      microduct-forming cell. The hypopharyngeal secretory cells possess an extremely
      elongate tubular invagination that is filled with a cuticular structure, the end
      apparatus, anchored against the cell membrane by a conspicuous series of actin
      rings. In contrast, venom glands have no actin rings, but instead have an actin
      rich brush border surrounding the comparatively short and narrow end-apparatus.
      We relate these cytoskeletal differences to the production system and utilisation
      of secretions; venom is stored in a reservoir whereas royal jelly and enzymes are
      produced on demand. Fluorescence-based characterisation of the actin cytoskeleton
      combined with scanning electron microscopy of the end-apparatus allows for
      detailed characterisation of the point of secretion release in insect class 3
      glands.

PMID- 23142090
TI  - Effect of sample volume size and sampling method on feline longitudinal
      myocardial velocity profiles from color tissue Doppler imaging.
AB  - OBJECTIVES: The aims of this study were to compare the effect of sample volume
      (SV) size settings and sampling method on measurement variability and peak
      systolic (s'), and early (e') and late (a') diastolic longitudinal myocardial
      velocities using color tissue Doppler imaging (cTDI) in cats. ANIMALS: Twenty
      cats with normal echocardiograms and 20 cats with hypertrophic cardiomyopathy.
      METHODS: We quantified and compared empirical variance and average absolute
      values of s', e' and a' for three cardiac cycles using eight different SV
      settings (length 1,2,3 and 5 mm; width 1 and 2 mm) and three methods of sampling
      (end-diastolic sampling with manual tracking of the SV, end-systolic sampling
      without tracking, and random-frame sampling without tracking). RESULTS: No
      significant difference in empirical variance could be demonstrated between most
      of the tested SVs. However, the two settings with a length of 1 mm resulted in a
      significantly higher variance compared with all settings where the SV length
      exceeded 2 mm (p < 0.001). There was an overall significant effect of sampling
      method on the variability of measurements (p = 0.003) and manual tracking
      obtained the lowest variance. No difference in average values of s', e' or a'
      could be found between any of the SV settings or sampling methods. CONCLUSION:
      Within the tested range of SV settings, an SV length of 1 mm resulted in higher
      measurement variability compared with an SV length of 3 and 5 mm, and should
      therefore be avoided. Manual tracking of the sample volume is recommended.

PMID- 23142091
TI  - Potential antioxidant properties and hepatoprotective effects of an aqueous
      extract formula derived from three Chinese medicinal herbs against CCl(4)-induced
      liver injury in rats.
AB  - The hepatoprotective effects of an aqueous extract formula (AEF) derived from
      Artemisia capillaris, Lonicera japonica and Silybum marianum (ratio 1:1:1) were
      evaluated by its antioxidant properties and its attenuation of carbon
      tetrachloride (CCl(4))-induced liver damage in rats. The antioxidant analyses
      revealed that the AEF showed higher 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical
      and superoxide anion radical scavenging activities as well as ferric reducing
      antioxidant potential (FRAP) and Trolox equivalent antioxidant capacity (TEAC)
      compared with the individual herbs, suggesting a synergism in antioxidation
      between the three herbs. The animal experiments showed that the CCl(4) treatment
      increased serum alanine aminotransferase (ALT) and aspartate aminotransferase
      (AST) activities, but decreased triglyceride (TG) and glutathione (GSH) levels as
      well as glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase
      (CAT) activities. However, AEF administration can successfully lower serum ALT
      and AST activities, restore the GSH level, ameliorate or restore GPx and CAT
      activities as well as improve SOD action depending on AEF dosage. Histological
      examination of liver showed that CCl(4) increased the extent of bile duct
      proliferation, necrosis, fibrosis and fatty vacuolation throughout the liver, but
      AEF can improve bile duct proliferation, vacuolation and fibrosis, and restore
      necrosis. The present study demonstrated the hepatoprotective potential of AEF as
      an alternative to the traditional silymarin.

PMID- 23142092
TI  - Induced apoptosis of Th2 lymphocytes and inhibition of airway hyperresponsiveness
      and inflammation by combined lactic acid bacteria treatment.
AB  - Several lactic acid bacteria (LAB) demonstrably regulate the immune system and
      inhibit allergic disease. This study examined whether oral feeding of either
      Lactobacillus paracasei (L. paracasei) BB5 and/or Lactobacillus rhamnosus (L.
      rhamnosus) BB1 suppresses ovalbumin (OVA)-induced airway hyperresponsiveness
      (AHR) and inflammation in a murine model. OVA-specific immune responses, cell
      profile of bronchoalveolar lavage fluid (BALF), and airway AHR were assessed
      following OVA and methacholine challenge. We investigated whether LAB can enhance
      CD4(+)FoxP3(+) and CD8(+)FoxP3(+) regulatory T (Treg) cells in splenic cells and
      apoptosis of CD4(+)IL-4(+) T cells. Results found oral administration of combined
      LAB better than single L. paracasei or L. rhamnosus strain, improving Penh ratio
      after challenge with methacholine. High-dose combined LAB starkly decreased
      synthesis of OVA-specific IgE and IgG2a levels, as well as eosinophils
      infiltration in BALF. In addition, CD4(+)IL-4(+) T cells decreased while
      CD4(+)FoxP3(+) and CD8(+)FoxP3(+) Treg cells increased significantly in splenic
      mononuclear cells of high-dose combined LAB group. Findings indicate allergen
      induced AHR and airway allergic inflammation suppressed by enhances
      CD4(+)FoxP3(+) and CD8(+)FoxP3(+) Treg populations as well as Th1 cell response
      after treating with combined LAB. This study may provide a basis for developing a
      novel therapeutic or protective method for airway allergic disease.

PMID- 23142093
TI  - Cell biology 2.0.

PMID- 23142094
TI  - The association between occlusal factors and noncarious cervical lesions: a
      systematic review.
AB  - OBJECTIVES: This study aimed to systematically review the scientific evidence for
      the association between noncarious cervical lesions (NCCL) and occlusal risk
      factors (ORF) [occlusal interferences in excursive movements; occlusal force;
      premature contacts; type of guidance; skid of centric occlusion to maximum
      intercuspidation] in adults. SOURCES: Pubmed, Web of Science, Cochrane, Lilacs,
      Clinical Trials, National Research Register and National Institute for Health
      were searched. STUDY SELECTION: From 1082 potentially eligible studies, 106 were
      selected for full text analysis. Two independent reviewers (Kappa=0.8; p<0.001)
      selected the studies, abstracted information and assessed quality based on
      standardised scales. Six cross-sectional, two case-controls and one clinical
      trial were included. Several occlusal variables were analysed among the studies,
      but there was no standardisation of the units used in the analysis of occlusal
      factors. The majority of studies did not find significant associations between
      NCCL and ORF. Three studies found associations between NCCL and some variables
      (occlusal contact area, right canine guidance, premature contacts in centric
      relation and working side) (p<0.05). The methodological quality varied across
      studies, and there was high heterogeneity among them. CONCLUSION: Current
      scientific evidence does not support an association between ORF and NCCL. Further
      prospective studies with standardised methods are vital to strengthen the
      evidence. CLINICAL SIGNIFICANCE: Understanding the risk factors for NCCL is
      important to control the causes and to help the dentist choose the best approach
      for the patient. The evidence does not support intervention to alter some
      occlusal factors for the prevention or control of the progression of NCCL.

PMID- 23142095
TI  - Influence of resin-based composite restoration technique and endodontic access on
      cuspal deflection and cervical microleakage scores.
AB  - OBJECTIVES: To assess cuspal deflection and cervical microleakage of mesio
      occlusal-distal cavities in standardised premolar teeth restored incrementally
      with resin-based composite (RBC) placed horizontally or obliquely and with
      endodontic access cavities (with and without gutta percha and epoxy resin sealer
      obturation). MATERIALS AND METHODS: Thirty-two teeth were allocated to four
      groups (n=8) and RBC restored in eight horizontal (Group A) or oblique increments
      (Groups B-D) using a quartz-tungsten-halogen light curing unit. The dependent
      variable for Groups B-D was endodontic access (none (Group B), obturated without
      (Group C) and with gutta percha and epoxy resin sealer (Group D)). Cuspal
      deflections were recorded post-irradiation using a twin channel deflection
      measuring gauge. Following restoration, the teeth were thermocycled, immersed in
      fuchsin dye, sectioned and examined for cervical microleakage. RESULTS: Tukey's
      post hoc tests identified a significant decrease in total cuspal deflection for
      the horizontal (p=0.015) compared with the oblique placement technique. No
      significant difference in total cuspal deflection was evident between Groups B
      and D restored teeth (p>0.318) or in cervical microleakage score between Groups A
      and D (p=0.575). SIGNIFICANCE: Deformation is proportional to the cubed power of
      the length of a uniform cantilever beam and although a crude approximation of
      cuspal deformation, the reduction in the effective cusp length therefore
      significantly reduced the deflection in the MOD cavities when the horizontal
      rather than the oblique incremental restoration technique was employed.

PMID- 23142096
TI  - Salivary proteins as a biomarker for dental caries--a systematic review.
AB  - AIM: To develop a systematic review based on the relation between salivary
      proteins and dental caries by comparing subjects with and without caries
      experience and to evaluate whether salivary proteins can be considered biomarkers
      for dental caries or not. METHODS: An electronic search was performed in the
      PubMed Medline, Ovid Medline, ISI Web of Science, Medline, Cochrane Library,
      Lilacs, Scielo, BBO, Paho and Wholis databases applying the following MeSH terms:
      "dental caries" OR "tooth demineralization" OR "dental caries susceptibility" OR
      "dental enamel solubility" AND "salivary proteins and peptides" OR "saliva" AND
      "proteins". To be eligible for the systematic review, the observational
      controlled studies had to have groups with and without caries experience. Studies
      with high risk of bias were excluded. RESULTS: From a total of 188 identified
      studies, only seven were included in this systematic review. Four studies were
      classified as "low risk of bias" and three as "moderate risk of bias". Three
      studies reported a relation between salivary proteins and dental caries.
      CONCLUSION: There was not sufficient evidence to establish salivary proteins as a
      biomarker for this disease although three of the seven studies showed a relation
      between salivary proteins and dental caries in terms of protein phenotypes, total
      protein concentration and protein molecular weight.

PMID- 23142097
TI  - Reducing violence in the emergency department: a rapid response team approach.

PMID- 23142098
TI  - A framework for creating and evaluating competencies for emergency nurses.

PMID- 23142099
TI  - Are temporal artery temperatures accurate enough to replace rectal temperature
      measurement in pediatric ED patients?
AB  - OBJECTIVE: This study examined the accuracy of temporal artery and axillary
      temperatures compared with rectal temperatures in pediatric ED patients younger
      than 4 years. METHODS: A method-comparison study design was used to examine the
      agreement between a temporal artery or axillary thermometer and a nondisposable,
      rectal electronic thermometer, which is the clinical reference standard for
      temperature measurement in children. Temperatures were taken with each device in
      a convenience sample of stable, pediatric ED patients who were younger than 4
      years. Bias and precision were calculated to quantify the differences between the
      2 devices, as well as the percentage of temporal artery and axillary temperatures
      that were >+/-1.0 degrees C and >+/-1.5 degrees C higher or lower than the rectal
      temperature. RESULTS: A total of 52 pediatric ED patients were studied over a 10
      month period. Bias and precision for the temporal artery and axillary devices
      were -0.46 degrees C +/- 0.50 degrees C and -0.93 degrees C +/- 0.49 degrees C,
      respectively. The percentage of temporal artery and axillary temperatures that
      were >+/-1.0 degrees C and/or >+/-1.5 degrees C above or below the clinical
      reference temperature were 15% and 6%, respectively, for the temporal artery
      thermometer and 39% and 14%, respectively, for the axillary thermometer.
      DISCUSSION: Bias and precision values for the temporal artery, but not the
      axillary temperature, were within the acceptable range set by experts to use as a
      noninvasive substitute for core body temperature measurements. If properly used
      by ED staff, temporal artery thermometers could be used to obtain temperature in
      pediatric patients younger than 4 years, thus avoiding physical and psychological
      discomfort for the child and parent associated with obtaining rectal
      thermometers.

PMID- 23142100
TI  - Response.

PMID- 23142101
TI  - Delivery of babies in the emergency department.

PMID- 23142102
TI  - Yet another piercing to play with: removal of surface anchors.

PMID- 23142103
TI  - Autoimmune neurological disorders associated with group-A beta-hemolytic
      streptococcal infection.
AB  - Although central nervous system (CNS) disorders associated with group-A beta
      hemolytic streptococcal (GABHS) infection occur only rarely, Sydenham's chorea is
      a well-recognized disease that can arise following infection. Children may
      develop a tic, obsessive compulsive disorder (OCD), and extrapyramidal movement
      subsequent to GABHS infection. These disorders have been termed pediatric
      autoimmune neuropsychiatric disorders associated with streptococci (PANDAS).
      Herein we report one case each of acute disseminated encephalomyelitis (ADEM),
      PANDAS and subacute encephalitis associated with GABHS infection. To evaluate the
      pathogenesis of the CNS disorders associated with GABHS infection, we measured
      levels of neurotransmitters, cytokines, anti-neuronal autoantibodies, and
      performed immunohistochemistry using patient sera to stain human brain sections.
      All three cases showed psychiatric behavioral disorders. Immunotherapy was
      effective, and homovanillic acid levels in the cerebrospinal fluid (CSF) were
      elevated at the acute stage in all three cases. In each case of ADEM and PANDAS,
      immunohistochemistry demonstrated neuronal impairment in the basal ganglia during
      the acute stage. Neuronal immunoreactivity was visualized in the cerebral cortex
      at the acute stage in the case of subacute encephalitis. There was no direct
      correlation between immunoreactivity of patient sera on the brain sections and
      positivity of anti-neuronal autoantibodies or CSF biomarkers. The results suggest
      that autoimmune responses may modulate neurotransmission, and the use of patient
      serum for immunohistochemistry is a sensitive screening method for the detection
      of anti-neuronal autoantibodies in CNS disorders associated with GABHS infection.

PMID- 23142104
TI  - Nanomedicine for the treatment of retinal and optic nerve diseases.
AB  - The earliest impact of nanomedicine in ophthalmology is likely to involve the
      areas of biopharmaceuticals, implantable materials (e.g. tissue regeneration
      scaffolds, bioresorbable materials), implantable devices (e.g. glaucoma drainage
      valves), and diagnostic tools (e.g. intraocular pressure (IOP) monitors).
      Nanotechnology will bring about the development of regenerative medicine (i.e.
      replacement and improvement of cells, tissues, and organs) and artificial vision.
      In this chapter, we review ophthalmic applications of nanotechnology in the
      following areas: drug and trophic factor therapy for glaucoma, retinal
      degenerative, and retinal vascular disease; gene therapy for retinal degenerative
      disease; regenerative medicine, including optogenetics and optic nerve
      regeneration; and diagnostics (minimally invasive IOP monitoring). Nanotechnology
      will play an important role in both early-stage and late-stage intervention in
      the management of blinding diseases.

PMID- 23142105
TI  - Evaluation of presumptive biomarkers of oxidative stress, immune response and
      apoptosis in primary open-angle glaucoma.
AB  - There is growing interest on the correlation among oxidative stress,
      inflammation, apoptosis and primary open-angle glaucoma initiation and
      progression. Reactive oxygen species are formed in the eyes following a wide
      variety of stressors, and are largely implicated in glaucoma pathogenesis. Immune
      inflammatory response mediators have recently become a target of ophthalmologic
      concern, including glaucoma. Much attention has been derived to the role of
      specific pro and anti-apoptotic molecules in glaucoma. This article reviews the
      early evidence suggesting that reactive oxygen species, immune inflammatory
      response mediators, and apoptogenic molecules are engaged in glaucoma disease.
      Moreover, further research concerning the functions, effectors and signaling
      pathways of the above molecules and their interactions, may lead to specifically
      develop targeted screening tools based on presumptive biomarkers and surrogate
      endpoints against primary open-angle glaucoma progression and blindness.

PMID- 23142106
TI  - Validation of a measure of knowledge about human papillomavirus (HPV) using item
      response theory and classical test theory.
AB  - OBJECTIVE: Public understanding of HPV is important to ensure informed
      participation in cervical cancer prevention programmes. While many studies have
      measured HPV knowledge, none has developed a validated measure for use across
      countries. We aimed to develop and validate such a measure. METHOD: Items tapping
      knowledge of HPV, HPV testing and HPV vaccination were developed from previous
      literature and with expert consultation. The 29-item measure was administered via
      the internet to 2409 adults in the UK, US and Australia in 2011. Classical test
      theory and item response theory were used to establish the measure's psychometric
      properties. RESULTS: Total scale reliability was very good (alpha = 0.838), as
      was internal consistency for a 16-item general HPV knowledge subset (alpha =
      0.849). Subsets of HPV testing and vaccination items showed reasonable test
      retest reliability (r(test-retest) = 0.62 and 0.69) but moderate internal
      consistency (alpha = 0.52 and 0.56). Dimensionality analyses suggested that one
      item was not measuring the same construct as the remainder of the questionnaire.
      A 2-parameter logistic item response theory (IRT) model was fitted to the
      remaining 28 scale items. CONCLUSIONS: A structurally coherent set of items
      covering a range of important HPV knowledge was developed. Responses indicated a
      reliable questionnaire, which allowed the fitting of an IRT model.

PMID- 23142108
TI  - Change is coming.

PMID- 23142109
TI  - A possible correlation between oxytocin-induced and angiotensin IV-induced anti
      hyperalgesia at the spinal level in rats.
AB  - In our previous study, we showed that intrathecal (i.t.) administration of
      angiotensin IV (Ang IV), an insulin-regulated aminopeptidase (IRAP) inhibitor,
      attenuated inflammatory hyperalgesia in rats. Using the plantar test in rats with
      carrageenan-induced paw inflammation, we investigated the possible mechanism(s)
      of this effect. Because i.t. oxytocin was reported to produce a dose-dependent
      anti-hyperalgesia in rats with inflammation, we speculate that there is a
      possible correlation between oxytocin-induced and Ang IV-induced anti
      hyperalgesia. Using i.t. co-administered atosiban (oxytocin receptor antagonist),
      the anti-hyperalgesia by Ang IV was completely abolished. This indicated that
      oxytocin could be the major IRAP substrate responsible for the anti-hyperalgesia
      by Ang IV. When Ang IV was co-administered with a low dose of oxytocin, there was
      a significant enhancing effect of Ang IV on oxytocin-induced anti-hyperalgesia.
      In recent reports, electrical stimulation on the paraventricular hypothalamic
      nucleus (PVN) was proved to increase oxytocin release at the spinal cord. Our
      results also showed that Ang IV could prolong the anti-hyperalgesia induced by
      PVN stimulation. This suggests a possible protective effect of Ang IV on
      endogenous oxytocin degradation/dysfunctioning. Moreover, we examined the local
      effect of intraplantarly injected Ang IV in the same model. Our results showed no
      effect of local Ang IV on hyperalgesia and paw edema, indicating that Ang IV may
      not regulate the peripheral inflammatory process. Overall, our study suggests
      that Ang IV may act through the inhibition of the activity of IRAP to reduce the
      degradation of oxytocin at the spinal cord, thereby leading to anti-hyperalgesia
      in rats with inflammation.

PMID- 23142110
TI  - Neuropeptide S stimulates human monocyte chemotaxis via NPS receptor activation.
AB  - Neuropeptide S (NPS) produces several biological actions by activating a formerly
      orphan GPCR, now named NPS receptor (NPSR). It has been previously demonstrated
      that NPS stimulates murine leukocyte chemotaxis in vitro. In the present study we
      investigated the ability of NPS, in comparison with the proinflammatory peptide
      formyl-Met-Leu-Phe (fMLP), to stimulate human monocyte chemotaxis. At a
      concentration of 10(-8)M fMLP significantly stimulated chemotaxis. NPS produced a
      concentration dependent chemotactic action over the concentration range 10(-12)
      to 10(-5)M. The NPSR antagonists [D-Cys((t)Bu)(5)]NPS, [(t)Bu-D-Gly(5)]NPS and
      SHA 68 were used to pharmacologically characterize NPS action. Monocyte
      chemoattractant effect of NPS, but not fMLP, was completely blocked by either
      peptide antagonists or SHA with the nonpeptide molecule being more potent. None
      of the NPSR antagonists modified per se random cell migration. Thus, the present
      study demonstrated that NPS is able to stimulate human monocyte chemotaxis and
      that this effect is entirely due to selective NPSR activation.

PMID- 23142111
TI  - Foreword: special issue cruse festschrift.

PMID- 23142112
TI  - Pushing short DNA fragments to the limit: Phylogenetic relationships of
      'hydrobioid' gastropods (Caenogastropoda: Rissooidea).
AB  - Although phylogenetic studies are increasingly utilizing multi-locus datasets, a
      review of GenBank data for the Gastropoda indicates a strong bias towards a few
      short gene fragments (most commonly COI, LSU rRNA, and SSU rRNA). This is
      particularly the case for the Rissooidea, one of the largest and most
      taxonomically difficult gastropod superfamilies. Here we analyze fragments of
      these three genes from 90 species to determine whether they can well resolve
      higher relationships within this superfamily, whether structurally aligned
      sequence datasets increase phylogenetic signal, and whether the inclusion of
      highly variable regions introduces noise. We also used the resulting phylogenetic
      data in combination with morphological/anatomical evidence to re-evaluate the
      taxonomic status of 'hydrobioid' family-level groups. Our results indicate that
      all three of the alignment strategies that were used resulted in phylogenies
      having similar signal levels. However, there was a slight advantage to using
      structural alignment for inferring family-level relationships. Moreover, the set
      of 'standard' gastropod genes supported recognition of many previously recognized
      families and provides new insight into the systematics of several problematic
      groups. However, some family-group taxa were unresolved and the relationships
      among families were also poorly supported, suggesting a need for more extensive
      sampling and inclusion of additional genes.

PMID- 23142113
TI  - Characterizing peritoneal dialysis catheter use in pediatric patients after
      cardiac surgery.
AB  - OBJECTIVE: Children who undergo cardiac surgery are at high risk for renal
      insufficiency and abdominal compartment syndrome. Peritoneal dialysis catheter
      (PDC) implantation is used in this population for abdominal decompression and
      access for dialysis. However, there is no consensus regarding PDC use, and the
      practice varies widely. This study was undertaken to assess associated factors,
      outcomes, and variability in the use of PDC in patients who have undergone
      cardiac surgery. METHODS: The cohort was obtained from the Kids' Inpatient
      Database, years 2006 and 2009. Patients who underwent cardiac surgery were
      included and the subset that underwent PDC implantation during the same
      hospitalization was identified. Univariable and multivariable analyses assessed
      factors associated with PDC and survival. RESULTS: A cohort of 28,259 patients
      underwent cardiac surgery, of whom 558 (2%) had PDCs placed. In the PDC group,
      39.1% (n = 218) had acute renal failure whereas 3.5% or patients (n = 974) in the
      non-PDC group had acute renal failure. Among patients receiving PDC, mortality
      was 20.3% (n = 113; vs 3.4% overall mortality, n = 955). Excluding patients with
      acute renal failure, mortality remained 12% (n = 41) for the PDC group. Factors
      associated significantly with PDC placement in the overall cohort were younger
      age, greater surgical complexity, nonelective admission, hospital region, use of
      cardiopulmonary bypass, and acute renal failure. CONCLUSIONS: Patients receiving
      PDC after cardiac surgery had 20% mortality, which remained 12% after excluding
      patients with acute renal failure. Given the variability in PDC use and poor
      outcomes, further research is needed to assess the possible benefit of earlier
      intervention for peritoneal access in this high-risk cohort.

PMID- 23142114
TI  - Acute left ventricular failure after bilateral lung transplantation for
      idiopathic pulmonary arterial hypertension.

PMID- 23142115
TI  - Esophageal complications of catheter ablation for atrial fibrillation: a case
      report.

PMID- 23142116
TI  - Hybrid total arch repair without deep hypothermic circulatory arrest for acute
      type A aortic dissection (R1).
AB  - OBJECTIVE: To investigate the surgical outcomes of hybrid total arch repair
      without deep hypothermic circulatory arrest for patients with acute Stanford type
      A aortic dissection. METHODS: Retrospective review of clinical data of patients
      with acute Stanford type A aortic dissection who underwent surgical repair at our
      institution between November 2009 and December 2011 identified 21 patients who
      underwent hybrid total arch repair without deep hypothermic circulatory arrest.
      The in-hospital and follow-up data were investigated. Postoperative serial
      computed tomography angiography was used to evaluate the fate of true and false
      lumen in arch and descending aorta. RESULTS: Mean follow-up was 13.8 months
      (range, 3 to 21 months). The 1- and 12-month survival rates (by Kaplan-Meier
      analysis) were 95.2% (95% confidence interval, 86.2%-100%) and 90.5% (95%
      confidence interval, 78.0%-100%), respectively. No endograft caudal migration
      occurred. One patient with type I endoleak was successfully resolved during
      operation. There was no late rupture or paraplegia. CONCLUSIONS: Hybrid total
      arch repair without deep hypothermic circulatory arrest offers a promising
      alternative to risk reduction of complications during the postoperative period
      and late adverse events resulting from false lumen enlargement in the arch and
      descending aorta.

PMID- 23142117
TI  - Nebulized nitrite protects rat lung grafts from ischemia reperfusion injury.
AB  - OBJECTIVES: Nebulization is a potential method for delivering therapeutic agents
      to lung grafts. Recent evidence suggests that nitrite may mitigate ischemia
      reperfusion injury via a nitric oxide-dependent pathway. METHODS: Syngeneic
      orthotopic left lung transplantation was performed in rats after 7 hours of cold
      ischemia. Sodium nitrite (3 mg) or phosphate-buffered saline (controls) was
      delivered before procurement via nebulization. RESULTS: Nitrite treatment was
      associated with better oxygenation, lower peak airway pressure, lower wet/dry
      ratio, reduced myeloperoxidase level and macrophage infiltration, increased
      cyclic guanosine monophosphate (cGMP) levels, and decreased levels of interleukin
      6, interleukin 1-beta, inducible nitric oxide synthase, and intercellular
      adhesion molecule-1 at 2 hours after reperfusion. Treatment with 2-(4
      carboxypheny)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, a nitric oxide
      scavenger, reversed the beneficial effects of nitrite and decreased cGMP
      concentration in grafts. A dose-response curve of nitrite was performed at the
      following doses: 0.3 mg (N0.1), 3.0 mg (N1.0), 5.25 mg (N1.75), 7.5 mg (N2.5),
      and 15.0 mg (N5.0). All treatments, excluding N1.0, resulted in poorer
      oxygenation, higher peak airway pressures, and higher wet/dry ratio. Higher
      dosage groups (N1.75, N2.5, and N5.0) exhibited positive immunostaining of
      nitrotyrosine and increased the intensity of nitrotyrosine in immunoblotting.
      CONCLUSIONS: These data suggest that nebulized nitrite limits lung ischemia
      reperfusion injury and may prove a clinically useful strategy but requires
      appropriate dosing to limit oxidative injury at high doses.

PMID- 23142118
TI  - Subcostal to rib-cross incision for HeartMate II explantation: a case report.

PMID- 23142119
TI  - National perioperative outcomes of pulmonary lobectomy for cancer in the obese
      patient: a propensity score matched analysis.
AB  - OBJECTIVES: Obesity in the United States is a growing epidemic that results in
      challenging patients with complicated comorbidities. We sought to compare
      hospital outcomes of obese patients with those of nonobese patients undergoing
      pulmonary lobectomy for cancer. METHODS: We performed a retrospective cohort
      analysis of obese (body mass index >= 30 kg/m(2)) and nonobese (body mass index <
      30 kg/m(2)) patients undergoing pulmonary lobectomy for lung cancer. By using the
      Nationwide Inpatient Sample database from 2002 to 2007, we determined independent
      risk factors for perioperative death, discharge to an institutional care
      facility, and prolonged hospital length of stay (>14 days). Cohorts were matched
      on the basis of propensity scores incorporating preoperative patient variables.
      RESULTS: We identified 1238 obese patients (3.7%) and 31,983 nonobese patients
      (96.3%) undergoing lobectomy for cancer. In regard to patient demographics, obese
      patients were younger (mean age, 64.8 vs 66.7, P < .001) and predominantly female
      (59.5% vs 50.0%, P < .001) compared with nonobese patients. After matching based
      on propensity scores, except for a greater incidence of pulmonary insufficiency
      (P = .03) and pneumonia (P = .01) in the obese group, there were no differences
      in postoperative complications. By controlling for patient demographics, obese
      patients had higher odds to be discharged to an institutional care facility (odds
      ratio, 1.21; P = .02) but not for prolonged hospital length of stay or
      perioperative death. CONCLUSIONS: Obese patients have an increased risk for
      postoperative pulmonary complications but not other morbidity, mortality, or
      prolonged hospital length of stay after lobectomy for cancer. Obesity should not
      be considered a surgical risk factor for pulmonary resection.

PMID- 23142120
TI  - Hybrid proximal surgery plus adjunctive retrograde endovascular repair in acute
      DeBakey type I dissection: superior outcomes to conventional surgical repair.
AB  - OBJECTIVE: The present study compared the outcomes between conventional surgery
      and the hybrid approach of proximal surgery with adjunctive retrograde descending
      aortic endografting plus distal bare metal stenting in acute DeBakey type I
      dissection. METHODS: From 2003 to 2011, 61 patients underwent surgical management
      for acute type A aortic dissection at our institution. Of these, 37 were DeBakey
      type I dissections: 18 patients (group 1) received conventional surgical repair
      alone, and 19 (group 2) underwent conventional hybrid surgery with adjunctive
      retrograde descending aortic stent grafting plus distal bare metal stenting.
      RESULTS: The patients' baseline characteristics were comparable, including the
      incidence of preoperative malperfusion syndromes (P = .23). The intraoperative
      and postoperative characteristics were similar, except 4 (22%) patients in group
      1 (vs 0 in group 2) had ongoing malperfusion postoperatively (P = .04). Overall,
      hospital mortality was 11% (n = 2) for group 1 versus 5% (n = 1) for group 2. At
      a mean follow-up of 50 months, 4 (25%) subjects in group 1 required secondary
      thoracoabdominal aortic reintervention versus none in group 2 (P = .03).
      CONCLUSIONS: The use of adjunctive retrograde descending aortic endografting plus
      distal bare metal stenting during acute DeBakey type 1 dissection repair is a
      feasible method to enhance thoracoabdominal remodeling. This hybrid strategy
      improves perioperative outcomes and decreases late distal aortic complications
      compared with conventional surgical repair for acute DeBakey type I dissection. A
      prospective, multicenter study is warranted to definitively assess this promising
      new treatment paradigm.

PMID- 23142122
TI  - Unilateral versus bilateral antegrade cerebral protection during circulatory
      arrest in aortic surgery: a meta-analysis of 5100 patients.
AB  - OBJECTIVE: Our objective was to determine whether the use of unilateral (u-ACP)
      or bilateral antegrade cerebral perfusion (b-ACP) results in different mortality
      and neurologic outcomes after complex aortic surgery. METHODS: PubMed, Embase,
      and the Cochrane Library were searched for studies reporting on postoperative
      mortality and permanent (PND) and temporary neurologic dysfunction (TND) in
      complex aortic surgery requiring circulatory arrest with antegrade cerebral
      protection. Analysis of heterogeneity was performed with the Cochrane Q
      statistic. RESULTS: Twenty-eight studies were analyzed for a total of 1894
      patients receiving u-ACP versus 3206 receiving b-ACP. Pooled analysis showed
      similar rates of 30-day mortality (8.6% vs 9.2% for u-ACP and b-ACP,
      respectively; P = .78), PND (6.1% vs 6.5%; P = .80), and TND (7.1% vs 8.8%; P =
      .46). Age, sex, and cardiopulmonary bypass time did not influence effect size
      estimates. Higher rates of postoperative mortality and PND were among nonelective
      operations and for highest temperatures and duration of the circulatory arrest.
      The Egger test excluded publication bias for the outcomes investigated.
      CONCLUSIONS: This meta-analysis shows that b-ACP and u-ACP have similar
      postoperative mortality and both PND and TND rates after circulatory arrest for
      complex aortic surgery.

PMID- 23142123
TI  - Dasatinib, a small molecule inhibitor of the Src kinase, reduces the growth and
      activates apoptosis in pre-neoplastic Barrett's esophagus cell lines: evidence
      for a noninvasive treatment of high-grade dysplasia.
AB  - BACKGROUND: Only local ablation (radiofrequency ablation, cryotherapy) or
      esophagectomy currently is available to treat high-grade dysplasia in Barrett's
      esophagus. Alternative treatments, specifically chemopreventive strategies, are
      lacking. Our understanding of the molecular changes of high-grade dysplasia in
      Barrett's esophagus offers an opportunity to inhibit neoplastic progression of
      high-grade dysplasia in Barrett's esophagus. Increased activity of the Src kinase
      and deregulation of the tumor suppressor p27 are features of malignant cells and
      high-grade dysplasia in Barrett's esophagus. Src phosphorylates p27, inhibiting
      its regulatory function and increasing cell growth and proliferation. We
      hypothesized that a small molecule inhibitor of Src might reduce the growth and
      reverse Src-mediated deregulation of p27 in Barrett's esophagus cells. METHODS:
      Immortalized Barrett's esophagus cell lines established from patient biopsies
      were treated with the Src kinase inhibitor dasatinib and evaluated for p27
      localization and protein levels, as well as for effects on the cell cycle and
      apoptosis using flow cytometry, viability assays, and protein and RNA markers.
      RESULTS: Dasatinib reduced both Src activation and p27 phosphorylation and
      increased p27 protein levels and nuclear localization. These effects correlated
      with decreased proliferation, cell-cycle arrest, and activation of apoptosis.
      Analysis of biopsies of patients with Barrett's esophagus revealed the presence
      of phosphorylated p27 in high-grade dysplasia, consistent with in vitro findings.
      CONCLUSIONS: Dasatinib has considerable antineoplastic effects on Barrett's
      esophagus cell lines carrying genetic markers associated with dysplasia, which
      correlates with the reversal of p27 deregulation. These findings suggest that
      dasatinib has potential as a treatment for patients with high-grade dysplasia and
      Barrett's esophagus and that p27 holds promise as a biomarker in the clinical use
      of dasatinib in patients with high-grade dysplasia and Barrett's esophagus.

PMID- 23142125
TI  - [Parkinsonian disorders: from clinical manifestations to diagnostic
      classification].
AB  - Parkinsonism may include atypical clinical manifestations, which are warning
      signs for the clinicians and motivate further investigations to identify an
      etiology other than idiopathic Parkinson's disease. The dismemberment of
      pathological entities, the advances of morphological and functional imaging of
      the brain, and new insights into molecular biology have successively led to more
      precise clinical phenotype and mechanisms. Except for etiologies with specific
      treatment, such as Wilson's disease or Parkinsonism secondary to a lesion of
      basal ganglia, or the discontinuation of a culprit drug, the treatment of
      Parkinsonian syndrome is mainly based on a multidisciplinary approach, involving
      occupational therapist, physiotherapist, speech therapist, psychologist and
      social worker. L-Dopa may be tried but it is less effective in atypical
      Parkinsonian syndrome than in Parkinson's disease. Formal diagnosis, only
      achievable post-mortem, is not available during the lifetime of the patient.
      Although some additional tests provide undeniable assistance, the clinical
      approach remains an essential and critical step to avoid costly and unnecessary
      investigations. 

PMID- 23142124
TI  - A shifting approach to management of the thoracic aorta in bicuspid aortic valve.
AB  - OBJECTIVES: The scientific understanding of aortic dilation associated with
      bicuspid aortic valve (BAV) has evolved during the past 2 decades, along with
      improvements in diagnostic technology and surgical management. We aimed to
      evaluate secular trends and predictors of thoracic aortic surgery among patients
      with BAV in the United States. METHODS: We used the 1998-2009 Nationwide
      Inpatient Sample, an administrative dataset representative of US hospital
      admissions, to identify hospitalizations for adults aged 18 years or more with
      BAV and aortic valve or thoracic aortic surgery. Covariates included age, gender,
      year, aortic dissection, endocarditis, thoracic aortic aneurysm, number of
      comorbidities, hospital teaching status and region, primary insurance, and
      concomitant coronary artery bypass surgery. RESULTS: Between 1998 and 2009,
      48,736 +/- 3555 patients with BAV underwent aortic valve repair or replacement
      and 1679 +/- 120 patients with BAV underwent isolated thoracic aortic surgery.
      The overall number of surgeries increased more than 3-fold, from 4556 +/- 571 in
      1998/1999 to 14,960 +/- 2107 in 2008/2009 (P < .0001). The proportion of aortic
      valve repair or replacement including concomitant thoracic aortic surgery
      increased from 12.8% +/- 1.4% in 1998/1999 to 28.5% +/- 1.6% in 2008/2009, which
      mirrored an increasing proportion of patients with a diagnosis of thoracic aortic
      aneurysm. Mortality was equivalent for patients undergoing aortic valve repair or
      replacement with thoracic aortic surgery and those undergoing isolated aortic
      valve repair or replacement (1.8% +/- 0.3% vs 1.5% +/- 0.2%; multivariable odds
      ratio, 1.02; 95% confidence interval, 0.67-1.57), with decreasing mortality over
      the study period (from 2.5% +/- 0.6% in 1998/1999 to 1.5% +/- 0.2% in 2008/2009;
      multivariable odds ratio per 2-year increment, 0.89; 95% confidence interval,
      0.81-0.99; P = .03). Total charges for BAV surgical hospitalizations increased
      more than 7.5-fold from approximately $156 million in 1998 to $1.2 billion in
      2009 (inflation-adjusted 2009 dollars). CONCLUSIONS: There was a marked increase
      in the use of thoracic aortic surgery among patients with BAV.

PMID- 23142126
TI  - [Interleukin-2 immunotherapy in autoimmune disorders].

PMID- 23142127
TI  - [High plasmatic concentration of vitamin B12: an indicator of hepatic diseases or
      tumors].
AB  - PURPOSE: To identify the diseases that are associated with a high plasma
      concentration of vitamin B12 and to measure the strength of this association.
      PATIENTS AND METHODS: Retrospective study including all admissions between 1st
      May, 2005 and 30th April, 2008 in the UMAG pole departments (emergency, internal
      medicine, acute geriatrics and medical intensive care) with a test for plasma
      vitamin B12. The association between each of medical information system codes
      (solid tumors, malignant hematologic process, and renal disease) and a high or
      low vitamin B12 concentration was measured by odds ratios (OR) from logistic
      models taking into account repeated admissions, with adjustment for age and the
      weighted Charlson index. RESULTS: Among 3702 admissions, 12% had a B12 more than
      820pg/ml, 10.4% a B12 less than 180pg/ml and 77.6% a normal B12 concentration.
      After adjustment for age and the weighted Charlson index, high concentration of
      vitamin B12 was associated with interstitial renal diseases (OR 2.7; 95% CI: [1.7
      4.2]), and cirrhosis or hepatitis (OR 4.3; [2.9-6.4]). After additional
      adjustment for these parameters, it was still associated with tumors (OR 1.8;
      [1.2-2.6]), malignant hematologic diseases (OR 2.1; [1.3-3.5]), metastasis (OR
      2.9; [1.5-5.9]), liver metastasis (OR 6.2; [2.7-14.5]), liver carcinoma (LC) (OR
      3.3; [1.1-10.4]), liver tumors other than LC (OR 4.7; [1.2-17.9]) and lymphoma
      (OR 3.2; [1.6-6.4]) but not with myeloma (OR 1.9; [0.6-1.4]). Low concentration
      of B12 was associated with myeloma (OR 2.9; [1.3-6.6]). CONCLUSION: Finding a
      high plasma concentration of vitamin B12 should lead to a systematic search for a
      hepatic disease or a tumor, and particularly for a hepatic localization of a
      tumor.

PMID- 23142128
TI  - Association between polymorphisms in erythropoietin gene and upper limit
      haematocrit levels among regular blood donors.
AB  - PURPOSE OF THE STUDY: Erythropoietin (EPO) is a glycoprotein hormone that
      functions primarily on the stimulation and control of erythropoiesis in bone
      marrow. In this study, polymorphisms in EPO gene; C3434T, G3544T (rs551238) and
      rs1617640 were evaluated to determine their frequencies and genotype distribution
      patterns among blood donors with upper-limit haematocrit level. SUBJECTS AND
      METHODS: A total of 298 subjects, 181 blood donors with haematocrit level greater
      or equal to 48% and 117 donors with haematocrit between 42-47.5% as control were
      recruited. All subjects were genotyped for C3434T, rs551238 polymorphisms and for
      rs1617640 using restriction fragment length polymorphism method (PCR-RFLP) and
      sequencing techniques. RESULTS: A significant difference was found in rs1617640
      and rs551238 genotype frequencies in blood donors with upper-haematocrit compared
      to the control group (P<0.05). In accordance with genotype frequencies, G allele
      in these two polymorphisms were found at higher frequency among upper-haematocrit
      group compared to the control (P<0.05). On the other hand, C3434T polymorphism
      was not significantly different between the two groups, neither for genotype
      frequencies nor for allele frequencies. CONCLUSION: Results suggest a strong
      association between rs551238 and rs1617640 polymorphisms in the EPO gene and
      upper-limit haematocrit level among blood donors.

PMID- 23142129
TI  - Caerulein precursor fragment (CPF) peptides from the skin secretions of Xenopus
      laevis and Silurana epitropicalis are potent insulin-releasing agents.
AB  - Peptidomic analysis of norepinephrine-stimulated skin secretions of the
      tetraploid clawed frog Xenopus laevis (Pipidae) led to the identification of 10
      peptides with the ability to stimulate the release of insulin from the rat BRIN
      BD11 clonal beta cell line. These peptides were purified to near homogeneity and
      structural characterization showed that they belong to the magainin (2 peptides),
      peptide glycine-leucine-amide (PGLa) (1 peptide), xenopsin precursor fragment (1
      peptide), and caerulein precursor fragment (CPF) (6 peptides) families. CPF-1,
      CPF-3, CPF-5 and CPF-6 were the most potent producing a significant (P < 0.05)
      increase in the rate of insulin release at concentration of 0.03 nM. CPF-7
      (GFGSFLGKALKAALKIGANALGGAPQQ) produced the maximum stimulation of insulin release
      (571 +/- 30% of basal rate at 3 MUM). In addition, CPF-SE1
      (GFLGPLLKLGLKGVAKVIPHLIPSRQQ), previously isolated from skin secretions of the
      tetraploid frog Silurana epitropicalis, produced a significant (P < 0.05)
      increase in the rate of insulin release at 0.03 nM with a 514 +/- 13% increase
      over basal rate at 3 MUM. No CPF peptide stimulated release of the cytosolic
      enzyme, lactate dehydrogenase from BRIN-BD11 cells at concentrations up to 3 MUM
      indicating that the integrity of the plasma membrane had been preserved. The
      mechanism of action of the CPF peptides involves, at least in part, membrane
      depolarization and an increase in intracellular Ca(2+) concentration. The CPF
      peptides show potential for development into agents for the treatment of Type 2
      diabetes.

PMID- 23142130
TI  - FhCaBP3: a Fasciola hepatica calcium binding protein with EF-hand and dynein
      light chain domains.
AB  - A DNA sequence encoding a protein with predicted EF-hand and dynein light chain
      binding domains was identified in a Fasciola hepatica EST library. Sequence
      analysis of the encoded protein revealed that the most similar known protein was
      the Fasciola gigantica protein FgCaBP3 and so this newly identified protein was
      named FhCaBP3. Molecular modelling of FhCaBP3 predicted a highly flexible N
      terminal region, followed by a domain containing two EF-hand motifs the second of
      which is likely to be a functioning divalent ion binding site. The C-terminal
      domain of the protein contains a dynein light chain like region. Interestingly,
      molecular modelling predicts that calcium ion binding to the N-terminal domain
      destabilises the beta-sheet structure of the C-terminal domain. FhCaBP3 can be
      expressed in, and purified from, Escherichia coli. The recombinant protein
      dimerises and the absence of calcium ions appeared to promote dimerisation.
      Native gel shift assays demonstrated that the protein bound to calcium and
      manganese ions, but not to magnesium, barium, zinc, strontium, nickel, copper or
      cadmium ions. FhCaBP3 interacted with the calmodulin antagonists trifluoperazine,
      N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide and chlorpromazine as well as
      the myosin regulatory light chain-binding drug praziquantel. Despite sequence and
      structural similarities to other members of the same protein family from F.
      hepatica, FhCaBP3 has different biochemical properties to the other well
      characterised family members, FH22 and FhCaBP4. This suggests that each member of
      this trematode calcium-binding family has discrete functional roles within the
      organism.

PMID- 23142131
TI  - Human papillomavirus vaccination in Auckland: reducing ethnic and socioeconomic
      inequities.
AB  - BACKGROUND: The New Zealand HPV publicly funded immunisation programme commenced
      in September 2008. Delivery through a school based programme was anticipated to
      result in higher coverage rates and reduced inequalities compared to vaccination
      delivered through other settings. The programme provided for on-going vaccination
      of girls in year 8 with an initial catch-up programme through general practices
      for young women born after 1 January 1990 until the end of 2010. OBJECTIVE: To
      assess the uptake of the funded HPV vaccine through school based vaccination
      programmes in secondary schools and general practices in 2009, and the factors
      associated with coverage by database matching. METHODS: Retrospective
      quantitative analysis of secondary anonymised data School-Based Vaccination
      Service and National Immunisation Register databases of female students from
      secondary schools in Auckland District Health Board catchment area. Data included
      student and school demographic and other variables. Binary logistic regression
      was used to estimate odds ratios and significance for univariables. Multivariable
      logistic regression estimated strength of association between individual factors
      and initiation and completion, adjusted for all other factors. RESULTS: The
      programme achieved overall coverage of 71.5%, with Pacific girls highest at 88%
      and Maori at 78%. Girls higher socioeconomic status were more likely be
      vaccinated in general practice. CONCLUSION: School-based vaccination service
      targeted at ethic sub-populations provided equity for the Maori and Pacific
      student who achieved high levels of vaccination.

PMID- 23142132
TI  - Non-clinical immuno-toxicological evaluation of HER1 cancer vaccine in non-human
      primates: a 12-month study.
AB  - Human epidermal growth factor receptor (HER1) constitutes a tumor associated
      antigen. Its overexpression in many epithelial tumors has been associated with
      bad prognosis and poor survival. Cancer vaccine based on the extracellular domain
      (ECD) of HER1 and adjuvated in very small sized proteoliposomes (VSSP) and
      Montanide ISA 51-VG is a new and complementary approach for the treatment of
      epithelial tumors. The present study deals with the immunogenicity of this
      vaccine in Macaca fascicularis monkeys and evaluation of its toxicity during 12
      months. Twelve monkeys were randomized into two groups of 3 animals per sex:
      control and vaccinated. Treated monkeys received 9 doses of vaccination and were
      daily inspected for clinical signs. Body weight, rectal temperature, cardiac and
      respiratory rates were measured during the study. Humoral immune response,
      clinical pathology parameters and delayed type hypensensitivity were analyzed.
      Skin biopsy was performed at the end of the study in all animals. Animal's
      survival in the study was 100% (n=12). Local reactions were observed at the
      administration site of four treated animals (n=6), with two showing slight
      inflammatory cutaneous damage. Clinical pathology parameters were not affected.
      HER1 vaccine induced high IgG antibodies titers in the treated animals even when
      DTH was not observed. The induced antibodies recognized HER1+ tumor cell lines,
      decreased HER1 phosphorylation and showed anti-proliferative and pro-apoptotic
      effects in H125 cells. In general the present study showed that HER1 vaccine
      induced specific immune response in M. fascicularis monkeys and was well
      tolerated, suggesting it could be safely used in clinical studies in epithelial
      cancer patients.

PMID- 23142133
TI  - Pathogen sensors and chemokine receptors in dendritic cell subsets.
AB  - Pathogen sensors such as Toll-like receptors (TLRs) detect microorganism- or host
      derived conserved molecular structures, including lipids or nucleic acids and
      provoke activation of Ag presenting cells such as dendritic cells (DCs). Several
      synthetic TLR ligands, especially oligonucleotides, are being developed as
      promising vaccines for infectious diseases, cancers or allergies. DCs are
      heterogeneous and consist of various subsets, each of which expresses a subset
      specific repertoire of TLRs and responds to the TLR signaling in a subset
      specific manner. Furthermore, each DC subset expresses a set of chemokine
      receptors that regulate its function and behavior. Here I review the functions of
      two DC subsets and how chemokine receptors function in these subsets. One is the
      plasmacytoid DC (pDC), which expresses nucleic acid sensing receptors TLR7 and
      TLR9 and secretes large amounts of type I interferons in response to TLR7/9
      signaling. The other is splenic CD8alpha(+) conventional DC (cDC). This DC subset
      expresses lipid sensors, TLR2 and TLR4, and nucleic acid sensors, TLR3, TLR9 and
      TLR13 and is specialized for antigen crosspresentation. Several chemokine
      receptors are differentially expressed on these DC subsets. The homologues of
      these murine DC subsets are also found in humans. Understanding how these DC
      subsets function and respond to TLR ligands and chemokines should be important
      for development of effective vaccines.

PMID- 23142134
TI  - WHO position paper on hepatitis A vaccines: June 2012-recommendations.
AB  - This article presents the World Health Organizations (WHO) recommendations onthe
      use of hepatitis A vaccine excerpted from the WHO position paper on hepatitis A
      vaccines - June 2012 recently published in the Weekly Epidemiological Record [1].
      The current document replaces the position paper on the use of hepatitis A
      vaccines published in 2000 [2] and incorporates the most recent developments in
      the field with particular consideration to changes in the epidemiological
      features of hepatitis A infection in several countries, increased supply of
      hepatitis A vaccines, and new evidence on their public health benefits. Footnotes
      to this paper provide a number of core references including references to grading
      tables that assess the quality of scientific evidence for a few key conclusions.
      In accordance with its mandate to provide guidance to Member States on health
      policy matters, WHO issues a series of regularly updated position papers on
      vaccines and combinations of vaccines against diseases that have an international
      public health impact. These papers are concerned primarily with the use of
      vaccines in large-scale immunization programmes; they summarize essential
      background information on diseases and vaccines, and conclude with WHO's current
      position on the use of vaccines in the global context. This paper reflects the
      recommendations of WHO's Strategic Advisory Group of Experts (SAGE) on
      immunization. These recommendations were discussed by SAGE at its November 2011
      and April 2012 meetings. Evidence presented at these meetings can be accessed at
      http://www.who.int/immunization/sage/previous/en/index.html.

PMID- 23142135
TI  - Phenotypic identification and classification of functional defecatory disorders
      using high-resolution anorectal manometry.
AB  - BACKGROUND & AIMS: Disordered defecation is attributed to pelvic floor
      dyssynergia. However, clinical observations indicate a spectrum of anorectal
      dysfunctions. The extent to which these disorders are distinct or overlap is
      unclear; anorectal manometry might be used in diagnosis, but healthy persons also
      can have abnormal rectoanal pressure gradients during simulated evacuation. We
      aimed to characterize phenotypic variation in constipated patients through high
      resolution anorectal manometry. METHODS: We evaluated anorectal pressures,
      measured with high-resolution anorectal manometry, and rectal balloon expulsion
      time in 62 healthy women and 295 women with chronic constipation. Phenotypes were
      characterized by principal components analysis of high-resolution anorectal
      manometry. RESULTS: Two healthy persons and 71 patients had prolonged (>180 s)
      rectal balloon expulsion time. A principal components logistic model
      discriminated healthy people from patients with prolonged balloon expulsion time
      with 75% sensitivity and a specificity of 75%. Four phenotypes discriminated
      healthy people from patients with abnormal balloon expulsion times; 2 phenotypes
      discriminated healthy people from those with constipation but normal balloon
      expulsion time. Phenotypes were characterized based on high anal pressure at rest
      and during evacuation (high anal), low rectal pressure alone (low rectal) or low
      rectal pressure with impaired anal relaxation during evacuation (hybrid), and a
      short anal high-pressure zone. Symptoms were not useful for predicting which
      patients had prolonged balloon expulsion times. CONCLUSIONS: Principal components
      analysis of rectoanal pressures identified 3 phenotypes (high anal, low rectal,
      and hybrid) that can discriminate among patients with normal and abnormal balloon
      expulsion time. These phenotypes might be useful to classify patients and
      increase our understanding of the pathogenesis of defecatory disorders.

PMID- 23142136
TI  - Factors that determine the antiviral efficacy of HCV-specific CD8(+) T cells ex
      vivo.
AB  - BACKGROUND & AIMS: Dysfunctional CD8(+) T cells are believed to contribute to the
      ability of hepatitis C virus (HCV) to evade the immune response. Most studies
      have focused on the effector functions of HCV-specific CD8(+) T cells or their
      surface expression of inhibitory receptors. There is currently no information
      available about the ex vivo ability of HCV-specific CD8(+) T cells to inhibit
      viral replication (antiviral efficacy). METHODS: To analyze the antiviral
      efficacy of virus-specific CD8(+) T cells ex vivo, we used an immunologic model
      based on a cell line that expresses HLA-A*02 and contains a stably replicating
      HCV reporter replicon. We isolated HCV-specific CD8(+) T cells from 18 HLA-A*02
      positive patients with chronic HCV infection and 15 subjects with resolved HCV
      infection (7 spontaneous, 8 after therapy). Replicon cells were labeled with
      virus-specific peptides; inhibition of HCV replication was determined by
      measuring luciferase activity after 72 hours of coculture with virus-specific
      CD8(+) T cells. RESULTS: HCV-specific CD8(+) T cells from patients with chronic
      HCV infection had a significantly lower antiviral efficacy than influenza-,
      Epstein-Barr virus-, and cytomegalovirus-specific CD8(+) T cells. Antiviral
      efficacy was associated with the ability of virus-specific CD8(+) T cells to
      secrete interferon gamma. The antiviral efficacy of HCV-specific CD8(+) T cells
      was linked to surface expression of CD127 and PD-1. The cytokines interleukin-2,
      interleukin-7, and interleukin-15 increased the antiviral efficacy of CD127
      positive but not of CD127-negative, HCV-specific CD8(+) T cells. Spontaneous, but
      not antiviral therapy-induced, viral clearance was associated with increased
      antiviral efficacy. CONCLUSIONS: The ability of CD8(+) T cells to inhibit HCV
      replication ex vivo is associated with their ability to secrete interferon gamma
      and their surface expression of CD127 and PD-1.

PMID- 23142137
TI  - Troy, a tumor necrosis factor receptor family member, interacts with lgr5 to
      inhibit wnt signaling in intestinal stem cells.
AB  - BACKGROUND & AIMS: The Wnt signaling pathway is required for maintenance of the
      intestinal epithelia; blocking this pathway reduces the proliferative capacity of
      the intestinal stem cells. However, aberrant Wnt signaling leads to intestinal
      cancer. We investigated the roles of the Wnt pathway in homeostasis of the
      intestinal epithelium and during malignant transformation in human cells and
      mice. METHODS: We performed chromatin immunoprecipitation (ChIP) with DNA
      microarray analysis (ChIP-on-chip) to identify genes regulated by Wnt signaling
      in human colorectal cancer cells Colo320, DLD1, LS174T, and SW480. Formation of
      intestinal tumor was induced in C57BL/6J mice using azoxymethane and dextran
      sulfate. Intestinal tissues from these mice, as well as Apc(+/Min) and
      Apc(CKO/CKO)/Lgr5-EGFP-IRES-CreERT2 mice, were analyzed by immunohistochemistry
      and in situ hybridization. RESULTS: We identified promoter regions of 960 genes
      that interacted with the Wnt pathway nuclear effector T-cell factor 4 in 4
      different human colorectal cancer-derived cell lines; 18 of these promoters were
      present in all chromatin precipitates. Wnt signaling up-regulated a member of the
      tumor necrosis factor receptor superfamily called TROY. Levels of TROY messenger
      RNA were increased in human cells with deficiencies in the adenomatous polyposis
      coli (APC) gene and in cells stimulated with the Wnt3a ligand. Expression of Troy
      was significantly up-regulated in neoplastic tissues from mice during intestinal
      tumorigenesis. Lineage tracing experiments revealed that Troy is produced
      specifically by fast-cycling intestinal stem cells. TROY associated with a unique
      marker of these cells, leucine-rich repeat-containing G-protein coupled receptor
      (LGR) 5. In organoids established from the intestinal crypts, Troy suppressed
      signaling mediated by R-spondin, a Wnt agonist. CONCLUSIONS: TROY is up-regulated
      in human colorectal cancer cell lines and in intestinal tumors in mice. It
      functions as a negative modulator of the Wnt pathway in LGR5-positive stem cells.

PMID- 23142138
TI  - Proceedings of the seminar on Emerging Infectious Diseases, November 9, 2011:
      current trends and proposals.

PMID- 23142139
TI  - Preparation and properties of photo-crosslinkable hydrogel based on
      photopolymerizable chitosan derivative.
AB  - Photopolymerizable chitosan derivative was synthesized by chitosan and methyl
      acroloyl glycine (MAG). The chemical structures and physical properties were
      characterized by FT-IR, (1)H NMR, XRD and TGA. The thermal stability of chitosan
      derivative was lower than chitosan. The chitosan derivative was amorphous
      compared with the high degree crystallization of chitosan. The hydrogels were
      prepared based on chitosan derivative via photopolymerization with different
      concentrations of photoinitiator 2959. The surface of hydrogel showed porous
      network and the pore size distribution tended to become homogeneous with the
      increase of the concentration of 2959, while the swelling property decreased due
      to more crosslinking.

PMID- 23142140
TI  - Stability of halophilic proteins: from dipeptide attributes to discrimination
      classifier.
AB  - To investigate the molecular features responsible for protein halophilicity is of
      great significance for understanding the structure basis of protein halo
      stability and would help to develop a practical strategy for designing halophilic
      proteins. In this work, we have systematically analyzed the dipeptide composition
      of the halophilic and non-halophilic protein sequences. We observed the
      halophilic proteins contained more DA, RA, AD, RR, AP, DD, PD, EA, VG and DV at
      the expense of LK, IL, II, IA, KK, IS, KA, GK, RK and AI. We identified some
      macromolecular signatures of halo-adaptation, and thought the dipeptide
      composition might contain more information than amino acid composition. Based on
      the dipeptide composition, we have developed a machine learning method for
      classifying halophilic and non-halophilic proteins for the first time. The
      accuracy of our method for the training dataset was 100.0%, and for the 10-fold
      cross-validation was 93.1%. We also discussed the influence of some specific
      dipeptides on prediction accuracy.

PMID- 23142141
TI  - Effects of buccal and lingual enamel sandblasting on shear bond strength of
      orthodontic brackets bonded with a self-etching primer.
AB  - The purpose of this study was to evaluate the effects of sandblasting on the
      initial shear bond strength (SBS) and on the bracket/adhesive failure mode of
      orthodontic brackets bonded on buccal and lingual enamel using a self-etching
      primer (SEP). The brackets were bonded using a SEP and composite resin on the
      buccal and lingual surfaces of 30 premolars with intact enamel and 30 premolars
      pretreated by sandblasting with 50 MUm aluminum-oxide. Student's paired t-test
      was used to compare the groups for differences in SBS and a multiple Chi(2) test
      was performed to compare the bond failure mode. It was shown that sandblasting
      increases significantly SBS of the SEP on the buccal surfaces but the increase on
      the lingual surfaces is not statistically significant. A comparison of the
      adhesive remnant index scores indicated that there was more residual adhesive
      remaining on the teeth that were treated by sandblasting than on the teeth with
      intact enamel. Besides, there is no statistical difference between SBS of the SEP
      on buccal and lingual surfaces with intact enamel. Therefore, we can conclude
      that sandblasting improves the bond between buccal and lingual enamel and resin
      ant that the SEP provides the same SBS on buccal and lingual intact surfaces.

PMID- 23142143
TI  - Noxious stimulation excites serotonergic neurons: a comparison between the
      lateral paragigantocellular reticular and the raphe magnus nuclei.
AB  - The present study was designed to record electrophysiological responses to graded
      noxious thermal stimuli of serotonergic and nonserotonergic neurons in the
      lateral paragigantocellular reticular (LPGi) and the raphe magnus (RMg) nuclei in
      rats. All of the neurons recorded were juxtacellularly filled with neurobiotin
      and identified with double immunofluorescent labeling for both neurobiotin and
      serotonin. Under halothane anesthesia (0.75%), noxious thermal stimuli ?48
      degrees C activated almost all (88%) of the serotonergic neurons located within
      the LPGi (n=16). The increase in firing was clear (3.4+/-0.3spike/s: mean of
      responses above the population median) and sustained during the whole application
      of strong thermal noxious stimuli, with a high mean threshold (48.3+/-0.3 degrees
      C) and large receptive fields. Recording of serotonergic neurons in the RMg
      (n=21) demonstrated that the proportion of strongly activated (>2spike/s) neurons
      (19% vs 59% for the LPGi) as well as the magnitude of the activation (2.1+/
      0.4spike/s: mean of responses above the population median) to thermal noxious
      stimuli were significantly lower than in the LPGi (P<.05). Within the boundaries
      of both the LPGi and the RMg (B3 group), nonserotonergic neurons were also
      predominantly excited (75%) by noxious stimuli, and the resulting activation
      (7.9+/-1.2spike/s) was even greater than that of serotonergic neurons. Thermal
      noxious stimuli-induced activation of LPGi serotonergic cells probably plays a
      key role in serotonin-mediated modulations of cardiac baroreflex and transmission
      of nociceptive messages occurring under such intense noxious conditions.

PMID- 23142144
TI  - Low calcium intake and inadequate vitamin D status in postmenopausal osteoporotic
      women.
AB  - An observational cross-sectional study was conducted to assess calcium intake and
      vitamin D status by measurement of 25-hydroxyvitamin D (25(OH)D), in
      postmenopausal osteoporotic women (PMOW) treated and untreated for osteoporosis.
      To assess the influence of sunlight exposure on vitamin D status, the study group
      was categorized on the basis of sunlight exposure (above or below 2500 sunlight
      h/year). A group of 336 PMOW older than 65 years was identified (190 [56.5%]
      treated and 146 [43.5%] untreated for osteoporosis). The demographic and clinical
      data of the PMO women included history of prior fractures, pharmacological
      treatments and dietary calcium intake. BMD was measured by DEXA and 25(OH)D was
      determined by an HPLC method. RESULTS: vitamin D serum levels were lower in the
      untreated group as compared with the treated group (58+/-27 vs. 67+/-27nmol/l;
      p=0.006). Prevalence of vitamin D deficiency (cut-off point set at <50nmol/l) was
      higher in the non-treated group (43.8% vs. 29.5%; p=0.009). Nearly all PMOW,
      whether treated or not for osteoporosis had a total calcium intake of less than
      1200mg. Sunlight exposure did not influence the vitamin D status. CONCLUSIONS:
      vitamin D deficiency and an insufficient calcium intake are highly prevalent in
      both treated and untreated Spanish PMOW older than 65 years. This can be related
      to low therapeutic adherence and/or insufficient prescription. Therefore
      physician's and patient's knowledge regarding the optimization of vitamin D
      status and calcium intake should be improved and implemented. This article is
      part of a Special Issue entitled 'Vitamin D workshop'.

PMID- 23142145
TI  - EPR detection of paramagnetic chromium in liver of fish (Anguilla anguilla)
      treated with dichromate(VI) and associated oxidative stress responses
      contribution to elucidation of toxicity mechanisms.
AB  - The impact of chromium (Cr) on fish health has been the subject of numerous
      investigations, establishing a wide spectrum of toxicity, attributed particularly
      to the hexavalent form [Cr(VI)]. However, reports on the simultaneous assessment
      of Cr toxicity in fish and its toxico-kinetics, namely involving metal
      speciation, are scarce. Therefore, keeping in view the understanding of the
      mechanisms of Cr(VI) toxicity, this work intended to detect the formation of
      paramagnetic Cr species in liver of Anguilla anguilla following short-term
      dichromate(VI) intraperitoneal treatment (up to 180 min), assessing
      simultaneously the pro-oxidant properties. The formation of Cr(V) and Cr(III) was
      examined by electron paramagnetic resonance (EPR), as an innovative approach in
      the context of fish toxicology, and related with the levels of total Cr. Cr(V)
      was successfully detected and quantified by EPR spectrometry, showing a transient
      occurrence, mostly between 15 and 90 min post-injection, with a peak at 30 min.
      The limitations of EPR methodology towards the detection and quantification of
      Cr(III) were confirmed. Although Cr(VI) exposure induced the antioxidant system
      in the eel's liver, the oxidative deterioration of lipids was not prevented.
      Overall, the results suggested that Cr(V), as a short-lived species, did not
      appear to be directly and primarily responsible for the cellular damaging effects
      observed, since stress responses persisted up to the end of exposure regardless
      Cr(V) drastic decay. Though further research is needed, ROS mediated pathways
      (suggested by superoxide dismutase and catalase activity induction) and formation
      of Cr(III) complexes emerged as the most plausible mechanisms involved in Cr(VI)
      toxicity.

PMID- 23142146
TI  - Antiangiogenic, antimigratory and antiinflammatory effects of 2-methoxyestradiol
      in zebrafish larvae.
AB  - 2-Methoxyestradiol (2ME), an endogenous metabolite of 17beta-estradiol, has been
      previously reported to possess antiangiogenic and antitumor properties. Herein,
      we demonstrate that the effects of this antiangiogenic steroid can be readily
      assayed in live zebrafish, introducing a convenient and robust new model system
      as a screening tool for both single cell and collective cell migration assays.
      Using the in vitro mammalian endothelial cell line EA.hy926, we first show that
      cell migration and angiogenesis, as estimated by wound assay and tube formation
      respectively, are antagonized by 2ME. In zebrafish (Danio rerio) larvae, dose
      dependent exposure to 2ME diminishes (1) larval angiogenesis, (2) leukocyte
      recruitment to damaged lateral line neuromasts and (3) retards the lateral line
      primordium in its migration along the body. Our results indicate that 2ME has an
      effect on collective cell migration in vivo as well as previously reported anti
      tumorigenic activity and suggests that the molecular mechanisms governing cell
      migration in a variety of contexts are conserved between fish and mammals.
      Moreover, we exemplify the versatility of the zebrafish larvae for testing
      diverse physiological processes and screening for antiangiogenic and
      antimigratory drugs in vivo.

PMID- 23142147
TI  - Titanium ball joint total ossicular replacement prosthesis--experimental
      evaluation and midterm clinical results.
AB  - During reconstruction of the ossicular chain, there is a need to address the
      forces and loads caused by the ambient atmospheric pressure variations and the
      resulting tympanic membrane movements. It is understood that when a rigid middle
      ear prosthesis is inserted the malleoincudal joint, a keyfactor in controlling
      pressure variations in the middle ear space is bypassed. In this paper we
      describe a modified total titanium ossicular replacement prosthesis with an
      innovative micro ball joint in the headplate which is designed to compensate for
      tympanic membrane movements caused by atmospheric pressure variations. The
      characteristics of this modified prosthesis were examined in temporal bone
      experiments and compared to the standard titanium total ossicular reconstruction
      prosthesis. Sound-induced stapes footplate movements were investigated by means
      of a Laser vibrometer and revealed no significant differences between the two
      prostheses in vitro. Intraoperatively, the insertion of the modified prosthesis
      required more delicate handling. The angle between the shaft and the headplate
      was variable and ranged from 60 to 90 degrees  as estimated by the surgeon.
      Twelve consecutive patients were eligible for clinical evaluation. The pure tone
      average (PTA) air-bone gap after a mean follow up period of 32 months was 18.8
      dB. Furthermore, no extrusion, dislocation or other adverse events were observed.
      We conclude that the modified total ossicular replacement prosthesis with
      integrated micro ball joint yields similar volume velocities of the stapes
      footplate in the laboratory experiments compared to the standard rigid
      prosthesis. The audiological and morphological results are encouraging and show
      that the mobile prosthesis headplate adjusting to the level of the tympanic
      membrane is a further step in the development of a physiological middle ear
      implant. This article is part of a special issue entitled "MEMRO 2012".

PMID- 23142148
TI  - Ethnically diverse pluripotent stem cells for drug development.
AB  - Genetic variation is an identified factor underlying drug efficacy and toxicity,
      and adverse drug reactions, such as liver toxicity, are the primary reasons for
      post-marketing drug failure. Genetic predisposition to toxicity might be detected
      early in the drug development pipeline by introducing cell-based assays that
      reflect the genetic and ethnic variation of the expected treatment population.
      One challenge for this approach is obtaining a collection of suitable cell lines
      derived from ethnically diverse populations. Induced pluripotent stem cells
      (iPSCs) seem ideal for this purpose. They can be obtained from any individual,
      can be differentiated into multiple relevant cell types, and their self-renewal
      capability makes it possible to generate large quantities of quality-controlled
      cell types. Here, we discuss the benefits and challenges of using iPSCs to
      introduce genetic diversity into the drug development process.

PMID- 23142149
TI  - Taking diversity programs to the next level.
AB  - The Keystone Symposia Fellows Program is a unique and diverse research mentoring
      and positioning program tailored for 'end of the pipeline' scientists and can
      successfully enhance career advancement. Major program components include
      mentoring by well-established global science leaders and exposure to high-level
      discussions and decision making on future research priorities.

PMID- 23142150
TI  - Tumor necrosis factor and its targets in the inflammatory cytokine pathway are
      identified as putative transcriptomic biomarkers for escitalopram response.
AB  - Converging evidence suggests that the activation of the inflammatory cytokine
      pathway is important in the pathophysiology of unipolar depression.
      Antidepressants have anti-inflammatory properties and evidence suggests that
      inter-individual variability in response to antidepressants may reflect genetic
      differences in the inflammatory cytokine pathway. In particular, protein levels
      of Tumor Necrosis Factor (TNF) and the SNPs rs1126757 in interleukin-11 (IL11),
      and rs7801617 in interleukin-6 (IL6), have previously been implicated in the
      clinical response to the selective serotonin reuptake inhibitor (SSRI)
      antidepressant escitalopram. This study investigated the transcription of TNF,
      IL11 and IL6 as well as genes in the wider inflammatory cytokine pathway both at
      baseline and after escitalopram treatment in depressed patients who were either
      clinical "responders" (n=25) or "non-responders" (n=21). Samples were obtained as
      a subset of the Genome-Based Therapeutic Drugs for Depression (GENDEP) project
      and response status is based on changes in the Montgomery-Asberg Depression
      Rating Scores over a 12 wk treatment period. Binary logistic regressions revealed
      significant expression differences at baseline between responders and non
      responders in TNF, and after escitalopram treatment in TNF and IL11. Differences
      in IL11 after treatment were found to be driven by drug-induced allele-specific
      expression differences relating to rs1126757. Top hits in the wider inflammatory
      cytokine pathway at both baseline and after escitalopram treatment were found to
      be targets of TNF. The current study adds substantial support for the role of the
      inflammatory cytokine pathway in mediating response to the SSRI escitalopram, and
      is the first to identify TNF and its targets as putative transcriptomic
      predictors of clinical response.

PMID- 23142151
TI  - Oxidative and nitrosative stress in ammonia neurotoxicity.
AB  - Increased ammonia accumulation in the brain due to liver dysfunction is a major
      contributor to the pathogenesis of hepatic encephalopathy (HE). Fatal outcome of
      rapidly progressing (acute) HE is mainly related to cytotoxic brain edema
      associated with astrocytic swelling. An increase of brain ammonia in experimental
      animals or treatment of cultured astrocytes with ammonia generates reactive
      oxygen and nitrogen species in the target tissues, leading to
      oxidative/nitrosative stress (ONS). In cultured astrocytes, ammonia-induced ONS
      is invariably associated with the increase of the astrocytic cell volume.
      Interrelated mechanisms underlying this response include increased nitric oxide
      (NO) synthesis which is partly coupled to the activation of NMDA receptors and
      increased generation of reactive oxygen species by NADPH oxidase. ONS and
      astrocytic swelling are further augmented by excessive synthesis of glutamine
      (Gln) which impairs mitochondrial function following its accumulation in there
      and degradation back to ammonia ("the Trojan horse" hypothesis). Ammonia also
      induces ONS in other cell types of the CNS: neurons, microglia and the brain
      capillary endothelial cells (BCEC). ONS in microglia contributes to the central
      inflammatory response, while its metabolic and pathophysiological consequences in
      the BCEC evolve to the vasogenic brain edema associated with HE. Ammonia-induced
      ONS results in the oxidation of mRNA and nitration/nitrosylation of proteins
      which impact intracellular metabolism and potentiate the neurotoxic effects.
      Simultaneously, ammonia facilitates the antioxidant response of the brain, by
      activating astrocytic transport and export of glutathione, in this way increasing
      the availability of precursors of neuronal glutathione synthesis.

PMID- 23142152
TI  - Development of a pattern in biochemical parameters in the core and penumbra
      during infarct evolution after transient MCAO in rats.
AB  - The period from stroke initiation to the cessation of penumbra damage spread
      represents a therapeutic window when expansion can be alleviated. In the present
      work, we studied some biochemical parameters helpful for the estimation of
      infarct progression and thus for the application of interventions. We designed
      four groups: the control group and three groups of animals after middle cerebral
      artery occlusion with reperfusion periods of 2h, 1day or 3days. In the ischaemic
      core and penumbra, fluorimetric and spectrophotometric methods for investigating
      total MnSOD and MAO-A/B activity as well as level of the glutamate were used.
      Protein synthesis was assessed by in vitro measurements of (14)C-leucine
      incorporation. Noticeable differences between core and penumbra biochemical
      parameters were shown. In the core, protein synthesis was transiently inhibited
      two hours and three days after ischaemia (36%). Glutamate and total SOD activity
      peaked on the first day, but on the third day after MCAO, rapidly decreased by
      about 44% and 33.6%, respectively. In the penumbra, ischaemia led to higher
      protein synthesis (78%), elevations in glutamate and rapid activation of MnSOD
      (by about 884%) one day after insult. On the third day, protein synthesis and
      MnSOD were still significantly elevated (36% and 388%, respectively), while
      glutamate levels returned to baseline. In addition, the impact of ischaemia on
      MAO-A/B activity in the penumbra was confirmed. In conclusion, biochemical
      parameter screening could be helpful to assess cell damage progress and the
      possibility of rescue. These regions reflect different biochemical patterns that
      seem to be clearly established on the first day after transient MCAO. Moreover,
      the first day of post-ischaemic reperfusion in the present model of stroke seems
      to be the breakpoint, i.e. the time at which expanding cell death from the
      infarct core to the penumbra can be at least partially eliminated.

PMID- 23142153
TI  - Retinoic acid protects against proteasome inhibition associated cell death in SH
      SY5Y cells via the AKT pathway.
AB  - Inhibition of proteasome activity and the resulting protein accumulation are now
      known to be important events in the development of many neurological disorders,
      including Alzheimer's and Parkinson's diseases. Abnormal or over expressed
      proteins cause endoplasmic reticulum and oxidative stress leading to cell death,
      thus, normal proteasome function is critical for their removal. We have shown
      previously, with cultured SH-SY5Y neuroblastoma cells, that proteasome inhibition
      by the drug epoxomicin results in accumulation of ubiquitinated proteins. This
      causes obligatory loading of the mitochondria with calcium (Ca(2+)), resulting in
      mitochondrial damage and cytochrome c release, followed by programmed cell death
      (PCD). In the present study, we demonstrate that all-trans-retinoic acid (RA)
      pretreatment of SH-SY5Y cells protects them from PCD death after subsequent
      epoxomicin treatment which causes proteasome inhibition. Even though
      ubiquitinated protein aggregates are present, there is no evidence to suggest
      that autophagy is involved. We conclude that protection by RA is likely by
      mechanisms that interfere with cell stress-PCD pathway that otherwise would
      result from protein accumulation after proteasome inhibition. In addition,
      although RA activates both the AKT and ERK phosphorylation signaling pathways,
      only pretreatment with LY294002, an inhibitor of PI3-kinase in the AKT pathway,
      removed the protective effect of RA from the cells. This finding implies that RA
      activation of the AKT signaling cascade takes precedence over its activation of
      ERK1/2 phosphorylation, and that this selective effect of RA is key to its
      protection of epoxomicin-treated cells. Taken together, these findings suggest
      that RA treatment of cultured neuroblastoma cells sets up conditions under which
      proteasome inhibition, and the resultant accumulation of ubiquitinated proteins,
      loses its ability to kill the cells and may likely play a therapeutic role in
      neurodegenerative diseases.

PMID- 23142154
TI  - Effects of gliadin addition on the rheological, microscopic and thermal
      characteristics of wheat gluten.
AB  - In the present study, micro-structural, thermal and rheological changes in the
      gluten network upon addition of gliadins at 5% and 10% levels were investigated
      using scanning electron microscopy (SEM), thermo gravimetric analysis (TGA),
      differential scanning calorimetry (DSC) and dynamic rheometry. The addition of
      gliadins decreased the peak dough height inferring decrease in dough strength.
      The dough stability also decreased from 3.20 to 1.40 min upon addition of 10%
      gliadin to the base flour. The TGA profile and the glass transition behavior of
      the control gluten and gluten obtained from dough with gliadin added at 5% and
      10% levels showed decrease in thermal stability. The SEM micrograph of the
      control gluten showed foam like protein matrix. As the gliadin percentage in the
      gluten was increased, the compactness of the gluten structure reduced
      considerably leading to the formation of a more open weak gluten network.

PMID- 23142155
TI  - Denaturation and intermediates study of two sturgeon hemoglobins by n-dodecyl
      trimethylammonium bromide.
AB  - Varieties of hemoglobin (Hb) forms exist in fish, which are usually well adapted
      to the different ecological conditions or various habitats. In the current study,
      Hbs from two Sturgeon species of the Southern Caspian Sea Basin were purified and
      studied upon interaction with n-dodecyl trimethylammonium bromide (DTAB; as a
      cationic surfactant) by various methods including UV-visible absorption, dynamic
      light scattering (DLS), and ANS fluorescence spectrophotometry. The chemometric
      analysis of Hbs was investigated upon interaction with DTAB under titration,
      using UV-visible absorption spectra. The chemometric resolution techniques were
      used to determine the number of the components and mole fraction of the oxidized
      Hbs. These results provided the evidence for the existence of three different
      molecular components including native (N), intermediate (I) and denatured (D) in
      sturgeon Hbs. According to the distribution of intermediates, which were
      broadened in a range of DTAB concentration, the aggregation states, DLS
      experiments, and thermal stability (T(m) obtained by differential scanning
      calorimetry (DSC)), the Acipenser stellatus Hb was more stable compared to
      Acipenser persicus Hb. These results demonstrate a significant relationship
      between the stability of fish Hbs and the habitat depth requirements.

PMID- 23142156
TI  - Statins, systemic inflammation and risk of death in COPD: the Rotterdam study.
AB  - BACKGROUND: Studies suggest that statins decrease mortality in COPD patients but
      it is unknown which patients might benefit most. OBJECTIVES: We investigated
      whether statins were associated with reduced mortality in COPD patients and
      whether effects differed according to baseline high-sensitivity C-reactive
      protein (hsCRP) concentration, a marker of systemic inflammation. METHODS: This
      nested case-control study was part of the Rotterdam Study, a prospective
      population-based cohort study among 7983 subjects >= 55 years. Using automated
      pharmacy records, we evaluated statin use of 363 cases (COPD patients who died
      during follow-up of 17 years) with 2345 age and sex matched controls (COPD
      patients who survived the follow-up period of the index case). RESULTS: Compared
      to never use, long-term statin use (>2 years) was associated with a 39% decreased
      risk of death in COPD patients. Stratified according to the level of systemic
      inflammation, long-term statin use was associated with a 78% reduced mortality if
      hsCRP level > 3 mg/L, versus a non significant 21% reduced mortality if hsCRP
      level <= 3 mg/L. CONCLUSIONS: Statin use is associated with a beneficial effect
      on all-cause mortality in COPD, depending on the baseline level of systemic
      inflammation.

PMID- 23142157
TI  - Neural correlates of personality: an integrative review.
AB  - This review examines the neural correlates of Gray's model (Gray and McNaughton,
      2000; McNaughton and Corr, 2004), supplemented by a fourth dimension: constraint
      (Carver, 2005). The purpose of this review is to summarize findings from fMRI
      studies that tap on neural correlates of personality aspects in healthy subjects,
      in order to provide insight into the neural activity underlying human
      temperament. BAS-related personality traits were consistently reported to
      correlate positively to activity of the ventral and dorsal striatum and ventral
      PFC in response to positive stimuli. FFFS and BIS-related personality traits are
      positively correlated to activity in the amygdala in response to negative
      stimuli. There is limited evidence that constraint is associated with PFC and ACC
      activity. In conclusion, functional MRI research sheds some light on the specific
      neural networks underlying personality. It is clear that more sophisticated task
      paradigms are required, as well as personality questionnaires that effectively
      differentiate between BAS, FFFS, BIS, and constraint. Further research is
      proposed to potentially reveal new insight in the neural subsystems governing
      basic human behavior.

PMID- 23142158
TI  - Expression and localization of CERKL in the mammalian retina, its response to
      light-stress, and relationship with NeuroD1 gene.
AB  - Mutations in the Ceramide kinase like (CERKL) gene are associated with retinitis
      pigmentosa (RP26) and cone-rod dystrophy. CERKL is homologous to Ceramide kinase
      (CERK), and its function is still unknown. The purpose of this study was to test
      the expression and distribution of this gene and its protein in rat and in mouse
      tissues, in light-stressed rat retinas and in the retinas of NeuroD1 knock-out
      mice to understand the role of CERKL in the retina. Expression of Cerkl and Cerk
      mRNA was determined by quantitative RT-PCR. Expression of the protein was
      determined by Western blotting with anti-CERKL antibody. Localization of the
      protein was determined by using immunofluorescence microscopy. With qRT-PCR, we
      revealed that the relative mRNA expression of Cerkl was the highest in the retina
      among all the rat tissue tested; it was >10-fold higher than in the brain. On the
      other hand, Cerk has ubiquitous expression and its relative abundance is >2 fold
      of Cerkl in the retina. Cerkl was expressed minimally in the developing mouse
      eyes and reached a peak at retinal maturity at 2 months. Western blots of retinal
      tissues revealed two major CERKL protein bands: 59 kDa (C1) and 37 kDa (C2).
      However, only C2 CERKL was found in the rat retinal rod outer segment (ROS) at
      level of that was not changed in light vs. dark adaptation. In the light-stressed
      retina, expression of Cerkl mRNA increased significantly, which was reflected in
      only on C2 CERKL protein. The CERKL protein localized prominently to the ganglion
      cells, inner nuclear layers (INL), retinal pigment epithelial (RPE) cells, and
      photoreceptor inner segments in the retinal sections. Nuclear localization of
      CERKL was not affected in RPE, INL and the ganglion cell layers in the light
      stressed retina; however, the perinuclear and outer segment locations appear to
      be altered. In the NeuroD1 knock-out mouse retina, the expression of Cerkl mRNA
      and protein decreased and that decrease also pertains to C2 CERKL. In conclusion,
      the retina had the highest level of Cerkl mRNA and protein expression, which
      reached its maximum in the adult retina; CERKL localized to ROS and RPE cells and
      the light-adaptation did not change the level of CERKL in ROS; light-stress
      induced Cerkl expression in the retina; and its expression decreased in NeuroD1
      knock-out retina. Thus, CERKL may be important for the stress responses and
      protection of photoreceptor cells.

PMID- 23142159
TI  - Impact of socioeconomic status on diabetes and cardiovascular risk factors:
      results of a large French survey.
AB  - AIM: This study examined the association between deprivation and diabetes in a
      large French population, and evaluated the impact of deprivation on diabetes
      after taking in account a number of confounding factors. METHODS: A total of
      32,435 men and 16,378 women, aged 35 to 80 years, who had a health checkup at the
      "Centre d'Investigations Preventives et Cliniques" (IPC Centre: a preventive
      medical center in Paris, France), between January 2003 and December 2006, were
      evaluated. Socioeconomic deprivation was assessed using the EPICES score. The
      most deprived subjects were those in the fifth quintile of score distribution.
      RESULTS: Several cardiovascular risk markers increased significantly in deprived
      subjects. In both genders, deprivation was associated with deleterous health
      status and lifestyle habits. In women, BMI, central obesity and the metabolic
      syndrome were associated with deprivation. The prevalence of diabetes increased
      with deprivation level. Compared with the first quintile of EPICES score
      distribution, the prevalence of diabetes was three to eight times higher in the
      fifth quintile. After taking into account age, and biological, clinical and
      lifestyle parameters, the risk of diabetes onset (odds ratio) among deprived vs.
      non-deprived subjects was 2.54 (95% CI: 1.99-3.24) in men and 2.2 (95% CI: 1.44
      3.35) in women. CONCLUSION: In the general French population, deprivation was
      associated with deleterious health status and lifestyle. Risk of diabetes
      increased linearly with deprivation level and, after taking into account various
      confounding factors, the risk of diabetes remained significantly higher among
      deprived subjects. Other factors such as nutrition should now be examined to
      explain the excess risk of diabetes among the most deprived people.

PMID- 23142160
TI  - Modulation of the prolactin and the corticosterone stress responses: do they tell
      the same story in a long-lived bird, the Cape petrel?
AB  - Over the last decades, the corticosterone stress response has been suggested as a
      major physiological tool to understand what strategy an individual might adopt in
      response to environmental perturbations. More recently, another hormone related
      to parental care--prolactin--has been suggested as a complementary tool to
      investigate this question. Indeed, both of these hormones are affected by
      stressors and are involved in parental decisions, such as deserting the nest.
      Because of these similarities, it remains unclear what the functional distinction
      between the prolactin and corticosterone stress responses is. Here, we
      investigated whether natural variations of the corticosterone and prolactin
      stress responses are functionally linked in free-living Cape petrel (Daption
      capense) parents. If prolactin and corticosterone mediate the same functional
      response to a stressor and are the proxies of the same response, we predict that
      corticosterone and prolactin stress responses (1) will be modulated according to
      the same factors; (2) will affect reproductive performances in the same way; and,
      (3) of course, will be correlated. Contrary to these predictions, we found that
      the corticosterone and prolactin stress responses were respectively modulated
      according to body condition and breeding status. Moreover, prolactin levels, but
      not corticosterone levels, were related to hatching success in this species.
      Finally, we did not find any significant correlation between these two stress
      responses under any circumstances (failed breeders, incubating or chick rearing
      birds) and this result was overall supported by a review of the existing
      literature. Therefore, these two stress responses do not seem to be tightly
      linked and we believe that they may provide complementary pieces of information
      on parental investment in birds.

PMID- 23142161
TI  - Metabolic syndrome and arterial elasticity in youth.
AB  - OBJECTIVE: To compare arterial elasticity in children, adolescents, and young
      adults with and without metabolic syndrome (MetS), and to assess which MetS
      components, demographic measures, and body composition measures are associated
      with arterial elasticity. MATERIALS/METHODS: Two-hundred six subjects (107
      females and 99 males) between the ages of 10 and 20years were recruited by local
      newspaper advertisements, university email advertisements, and informational
      flyers. Subjects were assessed on MetS components, demographic measures, body
      composition measures, and arterial elasticity via radial tonometry. Forty-five
      subjects (22%) had MetS, as defined by the International Diabetes Federation, and
      161 subjects (78%) did not. RESULTS: The primary novel finding was that group
      differences were not observed for large artery elasticity index (LAEI)
      (MetS=16.1+/-4.4 (ml*mmHg(-1))*10 (mean+/-SD), control=15.4+/-4.9, (ml*mmHg(
      1))*10, p=0.349), and small artery elasticity index (SAEI) (MetS=9.2+/-2.7
      (ml*mmHg(-1))*100, control=8.4+/-2.9, (ml*mmHg(-1))*100, p=0.063). In the MetS
      group, fat free mass was positively associated with arterial elasticity, and was
      the strongest multivariate predictor of LAEI (partial R(2)=0.41) and SAEI
      (partial R(2)=0.29). CONCLUSIONS: Youth with MetS did not exhibit differences in
      LAEI and SAEI compared to controls. Furthermore, fat free mass of youth with MetS
      was positively associated with arterial elasticity, and was the strongest
      predictor of both LAEI and SAEI. The clinical implication is that exercise
      intervention designed to increase fat free mass might increase arterial
      elasticity in youth, particularly in youth with MetS.

PMID- 23142162
TI  - The influence of sodium- and calcium-regulatory hormone interventions on
      adipocytokines in obesity and diabetes.
AB  - OBJECTIVE: The renin-angiotensin-aldosterone system (RAAS), vitamin D, and
      parathyroid hormone have all been implicated as regulators of adipocytokines and
      inflammation. We evaluated human interventional study protocols to investigate
      whether controlled modulations of these calcium- and sodium-regulatory hormones
      could influence adipocytokines and inflammation in obesity and diabetes. METHODS:
      Post-hoc analyses of two separate human protocols (Protocol 1, n=14; Protocol 2,
      n=24) conducted in a clinical research setting after rigorous control of diet,
      posture, medications, and diurnal rhythm, were performed. Protocol 1 evaluated
      obese hypertensives with vitamin D deficiency who received an infusion of
      angiotensin II (AngII) before and after 1month of vitamin D3 therapy. Protocol 2
      evaluated obese subjects with type 2 diabetes who also received AngII.
      Adipocytokines and inflammatory markers were measured before and after vitamin D3
      therapy, and also before and after infusions of AngII. RESULTS: Vitamin D3
      therapy significantly raised 25(OH)D and 1,25(OH)2D concentrations, and lowered
      parathyroid hormone, but had no effect on concentrations of adiponectin,
      resistin, leptin, IL-6, PAI-1, urinary TGFbeta1, or HOMA-IR. AngII infusions,
      despite significant elevations in blood pressure and serum aldosterone, did not
      influence adipocytokine concentrations in either protocol. CONCLUSION: In
      contrast to prior studies conducted in healthy populations, or those that could
      not control major regulators of the RAAS or adipocytokines, we observed that
      robust modulations in calcium- and sodium-regulatory hormones did not influence
      adipocytokines or inflammation in obesity or diabetes. Adipose-tissue physiology
      in these conditions may alter the hormonal regulation of inflammatory parameters.

PMID- 23142163
TI  - Increased oxidative stress in normal-weight postmenopausal women with metabolic
      syndrome compared with metabolically healthy overweight/obese individuals.
AB  - OBJECTIVE: The purpose of this study was to assess whether the metabolically
      healthy overweight/obese phenotype is associated with decreased oxidative stress
      compared with normal-weight individuals with metabolic syndrome (MetS).
      MATERIALS/METHODS: Plasma oxidized LDL (ox-LDL) and urinary 8-epi-prostaglandin
      F2alpha (8-epi-PGF2alpha) were analyzed in a cross-sectional study of 1846
      healthy postmenopausal women. Participants were classified by presence (n=569) or
      absence (n=1277) of MetS and by BMI (18.5-24.9kg/m(2)=normal weight, n=1254;
      >=25kg/m(2)=overweight/obese, n=592). MetS was diagnosed with the modified
      National Cholesterol Education Program Adult Treatment Panel III criteria.
      RESULTS: Compared to normal weight women with MetS (n=296), metabolically healthy
      overweight/obese women (n=319) showed lower blood pressure, triglyceride, and
      glucose and higher HDL cholesterol, adiponectin, and LDL particle size. Ox-LDL
      was higher in overweight/obese women without MetS than in normal weight women
      without MetS (n=958) but was lower than in women with MetS. Urinary 8-epi
      PGF2alpha level was about 11% lower in women without MetS than in women with
      MetS. Normal weight women with MetS had greater odds of having ox-LDL
      (multivariate odds ratio [OR] 2.42, 95% CI: 1.65-3.55) and 8-epi-PGF2alpha (OR
      1.49; CI: 1.03-2.14) levels in the top quartile compared to normal weight women
      without MetS after adjusting for age, drinking, smoking, total- and LDL
      cholesterol, and high sensitivity C-reactive protein. Additionally, there was no
      significant correlation between ox-LDL and 8-epi-PGF2alpha. CONCLUSIONS: The
      metabolically healthy overweight/obese phenotype was associated with a better
      overall metabolic profile and less oxidative stress than that observed in normal
      weight individuals with MetS. Furthermore, there was a lack of association
      between ox-LDL and 8-epi-PGF2alpha.

PMID- 23142164
TI  - Response to: the important role of microRNAs in lipid metabolism.

PMID- 23142165
TI  - A comment on "Seralini, G.-E., et al., Long term toxicity of a Roundup herbicide
      and a Roundup-tolerant genetically modified maize. Food Chem. Toxicol. (2012),"
      http://dx.doi.org/10.1016/j.fct.2012.08.005.

PMID- 23142167
TI  - HIV-1 RNA shedding in the female genital tract is associated with reduced
      quantity of Lactobacilli in clinically asymptomatic HIV-positive women.
AB  - We quantified vaginal lactobacilli and determined their relationship with genital
      HIV-1 shedding and found a significant negative association between reduced
      quantity of lactobacilli and cervical HIV-1 viral load (r(2) = - 0.8900, P <
      0.01), which may have implications of increased chances of sexual transmission of
      HIV-1 and genital infections.

PMID- 23142166
TI  - Epidemiology, outcomes, and risk factors of invasive fungal infections in adult
      patients with acute myelogenous leukemia after induction chemotherapy.
AB  - This is a retrospective, single-center study of adult patients with newly
      diagnosed acute myelogenous leukemia (AML), who received intensive induction
      timed sequential chemotherapy from 1/2005 to 6/2010. Among 254 consecutive AML
      patients, 123 (48.4%) developed an invasive fungal infection (IFI): 14 (5.5%)
      patients with invasive candidiasis (IC) and 108 (42.5%) patients with invasive
      mould infections (IMI). Among 108 IMI identified, 4 (3.7%) were proven, 1 (0.9%)
      probable, and 103 (95.4%) were possible, using current definitions. Overall, 6
      month mortality was 23.7% (27/114) and 20.6% (26/126) for patients with and
      without an IFI, respectively. Older age (>=50 years; hazard ratio [HR]: 2.5, P <
      0.001), female gender (HR: 1.7, P = 0.006), and baseline renal and/or liver
      dysfunction (HR: 2.4, P < 0.001) were the strongest mortality predictors. We
      report relatively low rates of IC despite lack of routine primary antifungal
      prophylaxis, albeit associated with poor long-term survival. High rates of IMI,
      the vast majority with a possible diagnosis, were observed. Host-related
      variables (demographics and baseline organ dysfunction) were identified as the
      most significant risk factors for IFI and mortality predictors in this series.

PMID- 23142168
TI  - Comparison of the SUPERCARBA, CHROMagar KPC, and Brilliance CRE screening media
      for detection of Enterobacteriaceae with reduced susceptibility to carbapenems.
AB  - The recently developed SUPERCARBA medium was evaluated together with 2
      commercially available selective culture media containing carbapenems: CHROMagar
      KPC (CHROMagar) and Brilliance CRE (Oxoid, Thermofisher Scientific). A total of
      142 enterobacterial isolates were tested, including 131 isolates with reduced
      susceptibility to carbapenems. The SUPERCARBA medium has the highest sensitivity
      (96.5%) (detecting virtually all carbapenemase producers including OXA-48-like
      producers) as compared to Brilliance CRE (76.3%) and CHROMagar KPC (43%). The
      specificity of the screening media was similar, ranging from 57% to 68%.

PMID- 23142169
TI  - Model animals for the study of oxidative stress from complex II.
AB  - Mitochondria play a role of energy production and produce intracellular reactive
      oxygen species (ROS), especially superoxide anion (O2(-)) as a byproduct of
      energy metabolism at the same time. O2(-) is converted from oxygen and is
      overproduced by excessive electron leakage from the mitochondrial respiratory
      chain. It is well known that mitochondrial complexes I and III in the electron
      transport system are the major endogenous ROS sources. We have previously
      demonstrated that mutations in complex II can result in excessive ROS
      (specifically in SDHC: G71E in Caenorhabditis elegans, I71E in Drosophila and
      V69E in mouse). Moreover, this results in premature death in C. elegans and
      Drosophila as well as tumorigenesis in mouse embryonic fibroblast cells. In
      humans, it has been reported that mutations in SDHB, SDHC or SDHD, which are the
      subunits of mitochondrial complex II, often result in inherited head and neck
      paragangliomas (PGLs). Recently, we established Tet-mev-1 conditional transgenic
      mice using our uniquely developed Tet-On/Off system, which can induce the mutated
      SDHC gene to be equally and competitively expressed compared to the endogenous
      wild-type SDHC gene. These mice experienced mitochondrial respiratory chain
      dysfunction that resulted in oxidative stress. The mitochondrial oxidative stress
      caused excessive apoptosis in several tissues leading to low-birth-weight infants
      and growth retardation during neonatal developmental phase in Tet-mev-1 mice. Tet
      mev-1 mice also displayed precocious age-dependent corneal physiological changes,
      delayed corneal epithelialization, decreased corneal endothelial cells, thickened
      Descemet's membrane and thinning of parenchyma with corneal pathological
      dysfunctions such as keratitis, Fuchs' corneal dystrophy (FCD) and probably
      keratoconus after the normal development and growth phase. Here, we review the
      relationships between mitochondrial oxidative stress and phenomena in mev-1
      animal models with mitochondrial complex II SDHC mutations. This article is part
      of a Special Issue entitled: Respiratory complex II: Role in cellular physiology
      and disease.

PMID- 23142171
TI  - Gene therapy for cardiovascular disease: perspectives and potential.
AB  - Cardiovascular disease is the most frequent cause of mortality in the western
      world, accounting for over 800,000 premature deaths per year in the EU alone.
      Cardiovascular disease is the second most common application for gene therapy
      clinical trials, which most frequently employ adenovirus serotype 5 (Ad5)-based
      vectors as delivery vehicles. Although interactions of Ad5 vectors with
      circulating proteins and cells can limit their efficacy after systemic
      administration, local gene delivery strategies show great potential in the
      cardiovascular setting, notably in the context of vascular delivery. Here we
      review the pathogenesis of bypass graft failure and in-stent restenosis,
      identifying potential therapeutic targets and discussing recent advances in the
      field of adenovirus biology and retargeting that, in concert, will potentially
      translate in coming years to more effective gene therapies for cardiovascular
      applications.

PMID- 23142170
TI  - Mitochondrial complex II, a novel target for anti-cancer agents.
AB  - With the arrival of the third millennium, in spite of unprecedented progress in
      molecular medicine, cancer remains as untamed as ever. The complexity of tumours,
      dictating the potential response of cancer cells to anti-cancer agents, has been
      recently highlighted in a landmark paper by Weinberg and Hanahan on hallmarks of
      cancer [1]. Together with the recently published papers on the complexity of
      tumours in patients and even within the same tumour (see below), the cure for
      this pathology seems to be an elusive goal. Indisputably, the strategy ought to
      be changed, searching for targets that are generally invariant across the
      landscape of neoplastic diseases. One such target appears to be the mitochondrial
      complex II (CII) of the electron transfer chain, a recent focus of research. We
      document and highlight this particularly intriguing target in this review paper
      and give examples of drugs that use CII as their molecular target. This article
      is part of a Special Issue entitled: Respiratory complex II: Role in cellular
      physiology and disease.

PMID- 23142172
TI  - Nursing as first choice predicts nursing program completion.
AB  - BACKGROUND: Attrition from nursing programs is common, costly and burdensome to
      individuals, nursing faculties and the health care system. Increasingly, nursing
      faculties are requested to monitor attrition rates as a measure of performance,
      but little is known of the influence of career choice on program completion.
      OBJECTIVES: The aim of this study was to assess the impact of nursing as a first
      choice for study on attrition in a baccalaureate nursing program. DESIGN, SETTING
      AND PARTICIPANTS: A longitudinal, cohort design was used in this study, which
      involved undergraduate nursing students enrolled at a university in Australia. Of
      the 357 participants who completed a baseline survey in 2004 at entry to their
      Bachelor of Nursing program, 352 were followed up over a six-year period to the
      end of 2009. RESULTS: Students who selected nursing as their first choice for
      study were nearly twice as likely (OR: 1.99 95% CI: 1.07-3.68) to complete their
      nursing program compared to those who did not. These students were also more
      likely to be older (mean age: 26.8 vs 20.1years, P<0.001), and employed in
      nursing-related work (35% vs 2%, P<0.001). In addition, the study revealed that
      male students (OR: 1.93 95% CI: 1.07-3.46) and those who worked more than 16h per
      week during semester (OR: 1.80 95% CI: 1.09-2.99) were less likely to complete
      than their counterparts. CONCLUSIONS: These data assist in generating realistic
      projections of completion and entry to the workforce. Understanding patterns of
      attrition and individuals' motivations to be a nurse is important not only for
      supporting nursing students to help them complete their studies but also for
      developing more targeted strategies directed toward student recruitment and
      retention.

PMID- 23142173
TI  - Personal change amongst mental health nursing students: a longitudinal study.
AB  - BACKGROUND: Studies into the socialisation of nursing students have tended to
      concentrate on entrant's reactions to work and on the development of knowledge
      and skills in relation to a particular occupational culture. However, the extent
      and manner of personal and psychological changes experienced by mental health
      nursing students during occupational socialisation have yet to be thoroughly
      addressed in the literature. OBJECTIVES: To explore the psychological and
      personal changes of student mental health nurses over the first 2 years of their
      pre-registration mental health nursing programme. DESIGN: Students from 2 mental
      health nursing cohorts at a London university were invited to participate. A semi
      structured interview was used and the participants were asked to talk openly
      about their experiences. Ethics approval and informed consent was sought and
      obtained. PARTICIPANTS: 20 students were selected at random and invited to be
      interviewed on 5 occasions over a 2 year period at roughly 6 month intervals.
      METHODS: A total of 72 interviews were conducted. Interviews were tape recorded
      and verbatim transcribed for quantitative and qualitative content analyses.
      RESULTS: Participants described moving from feeling uncertain, to increasing
      awareness and understanding of self and others, and, ultimately, feeling more
      accomplished in relation to their occupational world. CONCLUSIONS: This study has
      highlighted the need for supporting students in developing their confidence and
      perceptions of self-efficacy and of recognising individual differences in
      student's responses to uncertainty.

PMID- 23142174
TI  - Psychological assessment and ongoing support is important to people with obesity:
      a role for nursing.

PMID- 23142175
TI  - Involvement of beta(3)-adrenergic receptors in in vivo cardiovascular regulation
      in rainbow trout (Oncorhynchus mykiss).
AB  - Currently, we have little information concerning the involvement of beta(3)
      adrenergic receptors (AR) in cardiovascular regulation in fishes. The goal of
      this study was to investigate the effect of beta(3)-AR ligands on in vivo
      cardiovascular function in larval and adult rainbow trout (Oncorhynchus mykiss).
      In adult fish, injection of BRL(37344) (beta(3)-AR agonist) resulted in an
      increase in heart rate (f(H)) (~31%) while stroke volume (Sv) was reduced (
      25.9%). Injection of SR(59230A) (beta(3)-AR antagonist) and propranolol
      (beta(1)/beta(2)-AR antagonist) resulted in increases in dorsal aorta blood
      pressure (P(DA)) with differing effect on cardiac variables (f(H) and Sv). To
      confirm specificity of the results, BRL(37344) was injected following sequential
      injections of phentolamine (alpha(1)-AR antagonist), atropine (muscarinic
      antagonist), propranolol and SR(59230A). While phentolamine had no effect on
      BRL(37344), atropine completely abolished the influence of BRL(37344) on f(H), Sv
      and cardiac output (Q). In larval trout, BRL(37344) (10 and 100 MUM) induced a
      significant concentration-dependent increase in f(H) while SR(59230A) (1 and 10
      MUM) and propranolol (1 and 10 MUM) separately caused a significant concentration
      dependent decrease. These data suggest that beta(3)-ARs have an important role in
      regulation of cardiovascular function, and provide evidence for a potential
      interaction between muscarinic and adrenergic receptors in rainbow trout.

PMID- 23142176
TI  - Molecular genetic investigations on Austria's patron saint Leopold III.
AB  - The successful marriage policy of margrave Leopold III increased the importance
      of the House of Babenberg in late medieval Austria (12th century). Historical
      documentation is inconclusive in providing evidence whether or not his eldest son
      Adalbert derived from an earlier relationship or from the marriage with King
      Henry IV's daughter Agnes of Waiblingen, with whom Leopold is considered to have
      had 17 children. As a matter of fact Adalbert was ignored in the line of
      succession in favor of a younger brother, Leopold IV, which has led to long term
      historical discussions. Human remains attributed to these individuals were
      subjected to DNA analysis. Autosomal, Y-chromosomal and mitochondrial DNA
      analyses brought successful results, which suggested that Leopold III, Agnes and
      Adalbert were related in parent-son constellation, in contrast to historical
      considerations. A possible mix-up of Adalbert's remains with those of his younger
      brother Ernst could not be confirmed by DNA analysis.

PMID- 23142177
TI  - Reply to letter: 'Is early hypothermia deleterious in comatose survivors to
      cardiac arrest?' and 'The optimal timing of initiation of therapeutic hypothermia
      after cardiac arrest'.

PMID- 23142178
TI  - Effect of simulated rainfall timing on faecal moisture and development of
      Haemonchus contortus and Trichostrongylus colubriformis eggs to infective larvae.
AB  - Three climate-controlled chamber experiments were conducted to determine the
      effect of 32 mm simulated rainfall applied prior to (days -4 to -1) or after
      (days 0-7) faecal deposition and as a single (32 mm) or split (2 * 16 mm)
      application on faecal moisture (FM) and development of H. contortus and T.
      colubriformis to third stage infective larvae (L3). The timing of simulated
      rainfall regulated extra-pellet L3 recovery for H. contortus (P<0.05) but not T.
      colubriformis. Recovery of L3 was highest (P<0.05) when simulated rainfall was
      applied on the day of deposition followed by days -1, 1 and 2, which resulted in
      similar but lower development success rates. Recovery of intra-pellet T.
      colubriformis L3 was two-fold greater (P=0.008) than for H. contortus and was
      higher (P=0.007) following simulated rainfall on days 0 and 1 than on other days.
      There was a positive association between FM and total L3 recovery indicating the
      importance of FM in the period 48-72 h (H. contortus) and 72-96 h (T.
      colubriformis) after deposition. Simulated rainfall on the day prior to
      deposition was as effective in supporting total L3 recovery as application on
      days 1 or 2 and this effect could be predicted through FM. This highlights the
      importance of soil in transferring moisture to the faecal pellet. The importance
      of precedent rainfall and soil moisture in determining the development success of
      H. contortus and T. colubriformis, in addition to the general effects of the
      timing of simulated rainfall, need to be accommodated in grazing management
      programs to combat these species.

PMID- 23142179
TI  - Prognostic factors of extremity soft tissue sarcoma in adults. A single
      institutional analysis.
AB  - PURPOSE: To analyse the prognostic factors for patients treated with limb sparing
      surgery and radiation for extremity soft tissue sarcoma (E-STS). PATIENTS AND
      METHODS: Medical records of 87 patients with limb sparing surgery and radiation
      for E-STS were reviewed retrospectively. Disease-free survival (DFS) and disease
      specific survival (DSS) were estimated and factors potentially influencing these
      outcomes were analysed. RESULTS: With a mean follow-up of 69months, most
      recurrences occurred within the first 2years. Extent of resection margin was
      found to improve DFS (P=0.002) and DSS (P=0.002). Brachytherapy combined with
      external beam radiotherapy (EBRT) improved DFS (P=0.034) and DSS (P=0.019). Tumor
      size (<10cm) was related to DSS (P=0.043) and its relation to DFS was almost
      significant (P=0.057). Short time interval between surgery and radiotherapy
      (<=50days) had an impact only on DSS (P=0.030). CONCLUSION: Extent of resection
      margin and use of brachytherapy combined with EBRT seem to improve the prognosis
      of E-STS. Small tumor size and short time interval between radiotherapy and
      surgery seem also to improve the outcome of E-STS. This study was limited by
      inadequate power and low number of recurrences. Larger randomised studies are
      needed to confirm these results.

PMID- 23142180
TI  - [Systematic approach for dysfunctional analysis in radiotherapy].
AB  - PURPOSE: We previously presented a systematic and structured approach to acquire
      an accurate functional model of the patient's process in radiotherapy. This
      approach relied on new functional structuring patterns, derived from system
      engineering and knowledge engineering. Additionally, we propose a complementary
      methodical process for the dysfunctional analysis of the obtained functional
      model. MATERIALS AND METHODS: The procedure is based on joint implementation of
      two qualitative methods named "Failure modes and effects analysis" (FMEA) and
      "Hazard and operability" (HazOp). RESULTS: All the technical, the human and the
      organizational dimensions of the patient's process are pooled in a unique,
      exhaustive and detailed dysfunctional analysis. The application of this
      systematic approach within a particular institution can precisely identify the
      risks incurred by patients in care, but also highlight the logical sequence
      between precursor events and incidents. CONCLUSION: The dysfunctional analysis
      presented in this document will be used for the development still in process of
      quantified risk models.

PMID- 23142181
TI  - A LED-based method for monitoring NAD(P)H and FAD fluorescence in cell cultures
      and brain slices.
AB  - Nicotinamide- and flavine-adenine-dinucleotides (NAD(P)H and FADH2) are electron
      carriers involved in cellular energy metabolism and in a multitude of enzymatic
      processes. As reduced NAD(P)H and oxidised FAD molecules are fluorescent, changes
      in tissue auto-fluorescence provide valuable information on the cellular redox
      state and energy metabolism. Since fluorescence excitation, by mercury arc lamps
      (HBO) is inherently coupled to photo-bleaching and photo-toxicity,
      microfluorimetric monitoring of energy metabolism might benefit from the
      replacement of HBO lamps by light emitting diodes (LEDs). Here we describe a LED
      based custom-built setup for monitoring NAD(P)H and FAD fluorescence at the level
      of single cells (HEK293) and of brain slices. We compared NAD(P)H bleaching
      characteristics with two light sources (HBO lamp and LED) as well as sensitivity
      and signal to noise ratio of three different detector types (multi-pixel photon
      counter (MPPC), photomultiplier tube (PMT) and photodiode). LED excitation
      resulted in reduced photo-bleaching at the same fluorescence output in comparison
      to excitation with the HBO lamp. Transiently increasing LED power resulted in
      reversible bleaching of NAD(P)H fluorescence. Recovery kinetics were dependent on
      metabolic substrates indicating coupling of NAD(P)H fluorescence to metabolism.
      Electrical stimulation of brain slices induced biphasic redox changes, as
      indicated by NAD(P)H/FAD fluorescence transients. Increasing the gain of PMT and
      decreasing the LED power resulted in similar sensitivity as obtained with the
      MPPC and the photodiode, without worsening the signal to noise ratio. In
      conclusion, replacement of HBO lamp with LED might improve conventional PMT based
      microfluorimetry of tissue auto-fluorescence.

PMID- 23142182
TI  - Three variations in rabbit angiographic stroke models.
AB  - PURPOSE: To develop angiographic models of embolic stroke in the rabbit using pre
      formed clot or microspheres to model clinical situations ranging from transient
      ischemic events to severe ischemic stroke. MATERIALS AND METHODS: New Zealand
      White rabbits (N=151) received angiographic access to the internal carotid artery
      (ICA) from a femoral approach. Variations of emboli type and quantity of emboli
      were tested by injection into the ICA. These included fresh clots (1.0-mm length,
      3-6h), larger aged clots (4.0-mm length, 3 days), and 2 or 3 insoluble
      microspheres (700-900 MUm). Neurological assessment scores (NAS) were based on
      motor, sensory, balance, and reflex measures. Rabbits were euthanized at 4, 7, or
      24h after embolization, and infarct volume was measured as a percent of total
      brain volume using 2,3,5-triphenyltetrazolium chloride (TTC). RESULTS: Infarct
      volume percent at 24 h after stroke was lower for rabbits embolized with fresh
      clot (0.45+/-0.14%), compared with aged clot (3.52+/-1.31%) and insoluble
      microspheres (3.39+/-1.04%). Overall NAS (including posterior vessel occlusions)
      were positively correlated to infarct volume percent measurements in the fresh
      clot (r=0.50), aged clot (r=0.65) and microsphere (r=0.62) models (p<0.001).
      CONCLUSION: The three basic angiographic stroke models may be similar to human
      transient ischemic attacks (TIA) (fresh clot), major strokes that can be
      thrombolysed (aged clot), or major strokes with insoluble emboli such as
      atheromata (microspheres). Model selection can be tailored to specific research
      needs.

PMID- 23142183
TI  - Management of scar contractures of the hand using Z advancement rotation flap.
AB  - Functional consequences of hand contractures may lead to extreme impairment in
      hand functions so repair of the contractures can solve the problems related to
      hand functions. Different forms of z plasties have widely been used for the
      release of scar contractures. In this study, a useful z plasty technique, z
      advancement rotation flap (ZAR) was adapted for the release of hand contractures
      in the way of using only local tissues. Fourteen consecutive patients who had
      hand contractures, were treated successfully with z advancement rotation flap
      technique. They suffered from hand contractures for at least one year which were
      localized in wep spaces, flexor surfaces of the digits, first wep space, palmar
      area and extensor surface of the hand. Contractures are all in mild severity,
      restricting some of the hand motions moderately. In all patients, hand
      contractures released completely and clinically normal joint motions were
      achieved, improving extension, flexion and abduction ranges of fingers without
      any difficulty. All advanced and rotated flaps healed uneventfully. No major
      complications appeared such as infection, hematoma, suture dehiscence, flap
      congestion or necrosis. When dealing with this technique for release of hand
      contractures, it may offer a versatile alternative to well known z-plasty methods
      used particularly for hand contractures. 

PMID- 23142184
TI  - Foot function is well preserved in children and adolescents with juvenile
      idiopathic arthritis who are optimally managed.
AB  - PURPOSE: The objective of this study was to compare disease activity,
      impairments, disability, foot function and gait characteristics between a well
      described cohort of juvenile idiopathic arthritis (JIA) patients and normal
      healthy controls using a 7-segment foot model and three-dimensional gait
      analysis. METHODS: Fourteen patients with JIA (mean (standard deviation) age of
      12.4 years (3.2)) and a history of foot disease and 10 healthy children (mean
      (standard deviation) age of 12.5 years (3.4)) underwent three-dimensional gait
      analysis and plantar pressure analysis to measure biomechanical foot function.
      Localised disease impact and foot-specific disease activity were determined using
      the juvenile arthritis foot disability index, rear- and forefoot deformity
      scores, and clinical and musculoskeletal ultrasound examinations respectively.
      Mean differences between groups with associated 95% confidence intervals were
      calculated using the t distribution. RESULTS: Mild-to-moderate foot impairments
      and disability but low levels of disease activity were detected in the JIA group.
      In comparison with healthy subjects, minor trends towards increased midfoot
      dorsiflexion and reduced lateral forefoot abduction within a 3-5 degrees  range
      were observed in patients with JIA. The magnitude and timing of remaining
      kinematic, kinetic and plantar pressure distribution variables during the stance
      phase were similar for both groups. CONCLUSION: In children and adolescents with
      JIA, foot function as determined by a multi-segment foot model did not differ
      from that of normal age- and gender-matched subjects despite moderate foot
      impairments and disability scores. These findings may indicate that tight control
      of active foot disease may prevent joint destruction and associated structural
      and functional impairments.

PMID- 23142185
TI  - Abnormal experimentally- and behaviorally-induced LTP-like plasticity in focal
      hand dystonia.
AB  - Idiopathic focal hand dystonia (FHD) arises from abnormal plasticity in the
      primary motor cortex (M1) possibly reflecting abnormal sensori-motor integration
      processes. In this transcranial magnetic stimulation (TMS) study in FHD, we
      evaluated changes in motor evoked potentials (MEPs) after intermittent theta
      burst stimulation (iTBS) and paired associative stimulation (PAS), techniques
      that elicit different forms of experimentally-induced long-term potentiation
      (LTP)-like plasticity in M1. We also examined behaviorally-induced LTP-like
      plasticity as reflected by early motor learning of a simple motor task. We
      studied 14 patients with FHD and 14 healthy subjects. MEPs were recorded before
      and after iTBS and PAS at the 25 ms interstimulus interval (PAS(25)) in separate
      sessions. Subjects did a simple motor task entailing repetitive index finger
      abductions. To measure early motor learning we tested practice-related
      improvement in peak velocity and peak acceleration. In FHD patients iTBS failed
      to elicit the expected MEP changes and PAS(25) induced abnormally increased MEPs
      in target and non-target muscles. In the experiment testing early motor learning,
      patients lacked the expected practice-related changes in kinematic variables. In
      FHD, the degree of early motor learning correlated with patients' clinical
      features. We conclude that experimentally-induced (iTBS and PAS) and behaviorally
      induced LTP-like plasticity are both altered in FHD.

PMID- 23142186
TI  - Over-expression of N-type calcium channels in cortical neurons from a mouse model
      of Amyotrophic Lateral Sclerosis.
AB  - Voltage-gated Ca(2+) channels (VGCCs) mediate calcium entry into neuronal cells
      in response to membrane depolarisation and play an essential role in a variety of
      physiological processes. In Amyotrophic Lateral Sclerosis (ALS), a fatal
      neurodegenerative disease caused by motor neuron degeneration in the brain and
      spinal cord, intracellular calcium dysregulation has been shown, while no studies
      have been carried out on VGCCs. Here we show that the subtype N-type Ca(2+)
      channels are over expressed in G93A cultured cortical neurons and in motor cortex
      of G93A mice compared to Controls. In fact, by western blotting,
      immunocytochemical and electrophysiological experiments, we observe higher
      membrane expression of N-type Ca(2+) channels in G93A neurons compared to
      Controls. G93A cortical neurons filled with calcium-sensitive dye Fura-2, show a
      net calcium entry during membrane depolarization that is significantly higher
      compared to Control. Analysis of neuronal vitality following the exposure of
      neurons to a high K(+) concentration (25 mM, 5h), shows a significant reduction
      of G93A cellular survival compared to Controls. N-type channels are involved in
      the G93A higher mortality because omega-conotoxin GVIA (1 MUM), which selectively
      blocks these channels, is able to abolish the higher G93A mortality when added to
      the external medium. These data provide robust evidence for an excess of N-type
      Ca(2+) expression in G93A cortical neurons which induces a higher mortality
      following membrane depolarization. These results may be central to the
      understanding of pathogenic pathways in ALS and provide novel molecular targets
      for the design of rational therapies for the ALS disorder.

PMID- 23142187
TI  - Folic acid prevents depressive-like behavior and hippocampal antioxidant
      imbalance induced by restraint stress in mice.
AB  - Experimental and epidemiological studies have shown the close relationship
      between stressful events, depression, and cognitive impairment. Folic acid has
      been reported to present antidepressant-like effects in both experimental and
      clinical approaches. However, the mechanisms mediating such effects are not
      understood. In the present study, we evaluated if folic acid administration to
      mice could protect against restraint stress-induced depressive-like behavior and
      cognitive deficit. Considering that oxidative stress has been pointed as a key
      event involved with depressive disorders, cerebrocortical and hippocampal
      oxidative stress-related parameters, such as the activities of antioxidant
      enzymes (mainly those related to the hydroperoxide-detoxifying system) and
      markers of lipid peroxidation, were also investigated. Restraint stress induced
      depressive-like behavior in the forced swimming test and memory impairment in the
      object recognition test, without altering locomotor activity of mice. Folic acid
      (50 mg/kg, p.o.) was able to prevent the stress-induced increase on immobility
      time in the forced swimming test, but did not prevent memory impairment.
      Moreover, restraint stress increased thiobarbituric acid reactive substance
      levels, and catalase, glutathione peroxidase and glutathione reductase activities
      in the cerebral cortex and hippocampus, and superoxide dismutase activity in the
      hippocampus. Folic acid treatment restored the activity of the antioxidant
      enzymes and reduced lipid peroxidation in the hippocampus. Glutathione, a non
      enzymatic antioxidant, was not altered by stress and/or folic acid
      administration. Together, the results of the present work reinforce the notion
      that folic acid displays a specific antidepressant profile in the restraint
      stress paradigm that may be at least partly due to its antioxidant role.

PMID- 23142188
TI  - Endoplasmic reticulum stress contributes to prediabetic peripheral neuropathy.
AB  - Growing evidence suggests that prediabetes and metabolic syndrome are associated
      with increased risk for the development of microvascular complications including
      retinopathy, nephropathy, and, most commonly, peripheral painful neuropathy
      and/or autonomic neuropathy. The etiology of these disabling neuropathies is
      unclear, and several clinical and experimental studies implicated obesity,
      impaired fasting glycemia/impaired glucose tolerance, elevated triglyceride and
      non-esterified fatty acids, as well as oxidative-nitrative stress. Endoplasmic
      reticulum stress resulting from abnormal folding of newly synthesized proteins
      and leading to the impairment of metabolism, transcriptional regulation, and gene
      expression, is emerging as a key mechanism of metabolic diseases including
      obesity and diabetes. We evaluated the role for this phenomenon in prediabetic
      neuropathy using two animal models i.e., Zucker (fa/fa) rats and high-fat diet
      fed mice which displayed obesity and impaired glucose tolerance in the absence of
      overt hyperglycemia. Endoplasmic reticulum stress manifest in upregulation of the
      glucose-regulated proteins BiP/GRP78 and GRP94 of unfolded protein response was
      identified in the sciatic nerve of Zucker rats. A chemical chaperone,
      trimethylamine oxide, blunted endoplasmic reticulum stress and alleviated sensory
      nerve conduction velocity deficit, thermal and mechanical hypoalgesia, and
      tactile allodynia. A selective inhibitor of eukaryotic initiation factor-2alpha
      dephosphorylation, salubrinal, improved glucose intolerance and alleviated
      peripheral nerve dysfunction in high-fat diet fed mice. Our findings suggest an
      important role of endoplasmic reticulum stress in the neurobiology of prediabetic
      peripheral neuropathy, and identify a new therapeutic target. 

PMID- 23142189
TI  - Monocytes and macrophages in malaria: protection or pathology?
AB  - Recruitment and activation of monocytes and macrophages are essential for
      clearance of malaria infection, but these have also been associated with adverse
      clinical outcomes. In this review we discuss recent discoveries on how distinct
      molecular interactions between monocytes, macrophages, and malaria parasites may
      alter the balance between protection and pathology in malaria-infected
      individuals. The immunopathology of severe malaria often originates from
      excessive immune activation by parasites. The involvement of monocytes and
      macrophages in these events is highlighted, and priorities for future research to
      clarify the roles of these cells in malaria are proposed. Knowledge of the
      factors influencing the balance between protection and pathology can assist in
      the design of therapeutics aimed at modulating monocyte and macrophage functions
      to improve outcomes.

PMID- 23142190
TI  - Efficient disruption of endogenous Bombyx gene by TAL effector nucleases.
AB  - Engineered nucleases are proteins that are able to cleave DNA at specified sites
      in the genome. These proteins have recently been used for gene targeting in a
      number of organisms. We showed earlier that zinc finger nucleases (ZFNs) can be
      used for generating gene-specific mutations in Bombyx mori by an error-prone DNA
      repair process of non-homologous end joining (NHEJ). Here we test the utility of
      another type of chimeric nuclease based on bacterial TAL effector proteins in
      order to induce targeted mutations in silkworm DNA. We designed three TAL
      effector nucleases (TALENs) against the genomic locus BmBLOS2, previously
      targeted by ZFNs. All three TALENs were able to induce mutations in silkworm
      germline cells suggesting a higher success rate of this type of chimeric enzyme.
      The efficiency of two of the tested TALENs was slightly higher than of the
      successful ZFN used previously. Simple design, high frequency of candidate
      targeting sites and comparable efficiency of induction of NHEJ mutations make
      TALENs an important alternative to ZFNs.

PMID- 23142191
TI  - Selective inhibitors of digestive enzymes from Aedes aegypti larvae identified by
      phage display.
AB  - Dengue is a serious disease transmitted by the mosquito Aedes aegypti during
      blood meal feeding. It is estimated that the dengue virus is transmitted to
      millions of individuals each year in tropical and subtropical areas. Dengue
      control strategies have been based on controlling the vector, Ae. aegypti, using
      insecticide, but the emergence of resistance poses new challenges. The aim of
      this study was the identification of specific protease inhibitors of the
      digestive enzymes from Ae. aegypti larvae, which may serve as a prospective
      alternative biocontrol method. High affinity protein inhibitors were selected by
      all of the digestive serine proteases of the 4th instar larval midgut, and the
      specificity of these inhibitors was characterized. These inhibitors were obtained
      from a phage library displaying variants of HiTI, a trypsin inhibitor from
      Haematobia irritans, that are mutated in the reactive loop (P1-P4'). Based on the
      selected amino acid sequence pattern, seven HiTI inhibitor variants were cloned,
      expressed and purified. The results indicate that the HiTI variants named T6
      (RGGAV) and T128 (WNEGL) were selected by larval trypsin-like (IC(50) of 1.1 nM)
      and chymotrypsin-like enzymes (IC(50) of 11.6 nM), respectively. The variants T23
      (LLGGL) and T149 (GGVWR) inhibited both larval chymotrypsin-like (IC(50) of 4.2
      nM and 29.0 nM, respectively) and elastase-like enzymes (IC(50) of 1.2 nM for
      both). Specific inhibitors were successfully obtained for the digestive enzymes
      of Ae. aegypti larvae by phage display. Our data also strongly suggest the
      presence of elastase-like enzymes in Ae. aegypti larvae. The HiTI variants T6 and
      T23 are good candidates for the development as a larvicide to control the vector.

PMID- 23142192
TI  - Evolutionary history of x-tox genes in three lepidopteran species: origin,
      evolution of primary and secondary structure and alternative splicing, generating
      a repertoire of immune-related proteins.
AB  - The proteins of the X-tox family have imperfectly conserved tandem repeats of
      several defensin-like motifs known as cysteine-stabilized alphabeta (CS
      alphabeta) motifs. These immune-related proteins are inducible and expressed
      principally in hemocytes, but they have lost the antimicrobial properties of the
      ancestral defensins from which they evolved. We compared x-tox gene structure and
      expression in three lepidopteran species (Spodoptera frugiperda, Helicoverpa
      armigera and Bombyx mori). Synteny and phylogenetic analyses showed that the x
      tox exons encoding CS-alphabeta motifs were phylogenetically closely related to
      defensin genes mapping to chromosomal positions close to the x-tox genes. We were
      able to define two groups of paralogous x-tox exons (three in Noctuids) that each
      followed the expected species tree. These results suggest that the ancestor of
      the three species already possessed an x-tox gene with at least two proto
      domains, and an additional duplication/fusion should have occurred in the
      ancestor of the two noctuid species. An expansion of the number of exons
      subsequently occurred in each lineage. Alternatively, the proto x-tox gene
      possessed more copy and each group of x-tox domains might undergo concerted
      evolution through gene conversion. Accelerated protein evolution was detected in
      x-tox domains when compared to related defensins, concomitantly to multiplication
      of exons and/or the possible activation of concerted evolution. The x-tox genes
      of the three species have similar structural organizations, with repeat motifs
      composed of CS-alphabeta-encoding exons flanked by introns in phase 1. Diverse
      mechanisms underlie this organization: (i) the acquisition of new repeat motifs,
      (ii) the duplication of preexisting repeat motifs and (iii) the duplication of
      modules. A comparison of gDNA and cDNA structures showed that alternative
      splicing results in the production of multiple X-tox protein isoforms from the x
      tox genes. Differences in the number and sequence of CS-alphabeta motifs in these
      isoforms were found between species, but also between individuals of the same
      species. Thus, our analysis of the genetic organization and expression of x-tox
      genes in three lepidopteran species suggests a rapid evolution of the
      organization of these genes.

PMID- 23142193
TI  - Reduced insular volume in attention deficit hyperactivity disorder.
AB  - The aim of this study was to evaluate whether structural differences in the
      insula and anterior cingulate cortex (ACC), two critical areas of the "salience
      network," co-exist in adolescents with attention deficit hyperactivity disorder
      (ADHD) compared with healthy controls (HC). In addition we aimed to determine if
      structural changes within these regions correlate with attention and inhibitory
      function. Nineteen adolescents with ADHD and 25 HC received MRI scans on a 3T
      magnet. Morphometric analysis was performed with FreeSurfer. Youths with ADHD
      were found to have a bilateral reduction in anterior insular (AIC) gray matter
      volumes compared to HC. Furthermore, the left AIC was found to positively
      correlate with oppositional symptoms, while the right AIC was found to associate
      with both attention problems and inhibition. To our knowledge this is the first
      report of a bilateral reduction in AIC volumes in ADHD. Our findings suggest a
      role for the insula in modulating attention and inhibitory capacity in ADHD.

PMID- 23142195
TI  - Predictors of mortality in patients with infections due to multi-drug resistant
      Gram negative bacteria: the study, the patient, the bug or the drug?
AB  - OBJECTIVE: To study the predictors of mortality among patients with multi-drug
      resistant Gram negative (MDRGN) infections and the role of MDRGN bacteria in the
      outcome of such patients. METHODS: PubMed and Scopus databases were searched
      (until June 30, 2012). Data were extracted and analyzed using the technique of
      meta-analysis. RESULTS: 30 studies (25 retrospective) were included in the
      analysis; 9 provided data on predictors of mortality for MDRGN infections only,
      while 21 provided data for MDRGN vs non-MDRGN infections. Acinetobacter spp were
      the most commonly studied bacteria followed by Pseudomonas aeruginosa and
      Enterobacteriaceae. Significant diversity was observed among studies regarding
      the evaluated predictors of mortality. Infection severity and underlying diseases
      were the most commonly reported independent predictors of mortality followed by
      multidrug resistance, inappropriate treatment and increasing age. In studies that
      included only patients with MDRGN infections, cancer (RR 1.65, 95% CI 1.13-2.39)
      and prior or current ICU stay (1.27, 1.02-1.56) were associated with mortality.
      In studies that included patients with MDRGN and non-MDRGN infections, septic
      shock (3.36, 2.47-4.57), ICU stay (2.15, 1.45-3.20), pneumonia (1.65, 1.09-2.52),
      isolation of MDRGN bacteria (1.49, 1.21-1.83), inappropriate definitive (2.05,
      1.12-3.76) and empirical treatment (1.37, 1.25-1.51), and male gender (1.13, 1.05
      1.21) were most commonly observed in patients who died than patients who
      survived. CONCLUSION: Significant diversity and statistical heterogeneity was
      observed. Beyond comorbidity and severity scores, MDR and inappropriate treatment
      were also identified as predictors of mortality.

PMID- 23142194
TI  - Localized differences in caudate and hippocampal shape are associated with
      schizophrenia but not antipsychotic type.
AB  - Caudate and hippocampal volume differences in patients with schizophrenia are
      associated with disease and antipsychotic treatment, but local shape alterations
      have not been thoroughly examined. Schizophrenia patients randomly assigned to
      haloperidol and olanzapine treatment underwent magnetic resonance imaging (MRI)
      at 3, 6, and 12 months. The caudate and hippocampus were represented as medial
      representations (M-reps); mesh structures derived from automatic segmentations of
      high resolution MRIs. Two quantitative shape measures were examined: local width
      and local deformation. A novel nonparametric statistical method, adjusted
      exponentially tilted (ET) likelihood, was used to compare the shape measures
      across the three groups while controlling for covariates. Longitudinal shape
      change was not observed in the hippocampus or caudate when the treatment groups
      and controls were examined in a global analysis, nor when the three groups were
      examined individually. Both baseline and repeated measures analysis showed
      differences in local caudate and hippocampal size between patients and controls,
      while no consistent differences were shown between treatment groups. Regionally
      specific differences in local hippocampal and caudate shape are present in
      schizophrenic patients. Treatment-related related longitudinal shape change was
      not observed within the studied timeframe. Our results provide additional
      evidence for disrupted cortico-basal ganglia-thalamo-cortical circuits in
      schizophrenia. CLINICAL TRIAL INFORMATION: This longitudinal study was conducted
      from March 1, 1997 to July 31, 2001 at 14 academic medical centers (11 in the
      United States, one in Canada, one in the Netherlands, and one in England). This
      study was performed prior to the establishment of centralized registries of
      federally and privately supported clinical trials.

PMID- 23142196
TI  - Mechanisms of anti-inflammatory property of Anacardium occidentale stem bark:
      inhibition of NF-kappaB and MAPK signalling in the microglia.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Anacardium occidentale is used in traditional
      African medicine for the treatment of arthritis, fever, aches, pains, and
      inflammation of the extremities. AIM OF THE STUDY: In this study, we investigated
      the molecular mechanisms responsible for anti-inflammatory effects of a stem bark
      extract of A. occidentale (ANE) in LPS-stimulated microglia. MATERIALS AND
      METHODS: Nitric oxide (NO), prostaglandin E(2) and cytokine (TNFalpha and IL-6)
      production were evaluated in supernatants from LPS-stimulated BV-2 cells.
      Cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and microsomal
      prostaglandin E2 synthase (mPGES-1) protein expressions in rat primary microglia
      were measured using western blot. The effects of ANE on NF-kappaB activation and
      nuclear translocation were evaluated in the luciferase reporter gene assay and
      ELISA, while ability of ANE to influence IkappaB phosphorylation was determined
      using ELISA specific for phospho-IkappaB. The involvement of MAPK phosphorylation
      in the anti-inflammatory actions of ANE was evaluated using specific ELISA for
      phospho-p38, phospho-p42/44 and phospho-JNK. The MTT assay was used to determine
      the effect of ANE on BV-2 microglia viability. RESULTS: ANE (25-100 MUg/ml)
      produced significant (p<0.05) reduction in the production of NO, PGE(2), TNFalpha
      and IL-6 in BV-2 microglia stimulated with LPS for 24h. Pre-treatment with ANE
      caused a significant (p<0.05) inhibition of COX-2, iNOS and mPGES-1 protein
      expressions in the rat primary microglia. Further experiments showed that ANE
      inhibited COX-2 and iNOS protein expression via IkappaB-mediated nuclear
      translocation and transactivation of NF-kappaB. Our studies also revealed that
      ANE produced significant (p<0.05) and dose-dependent inhibition of p38, p42/44
      and JNK MAPK phosphorylation in LPS-activated BV-2 microglia. CONCLUSIONS: We
      conclude that ANE has an anti-inflammatory property related to inhibition of
      inflammation-associated cytokine production as well as iNOS and COX-2 gene
      expression by blocking NF-kappaB and MAPK pathways in the microglia. It is also
      suggested that mPGES-1 inhibition contributes to the effect of ANE on PGE(2)
      production in the microglia.

PMID- 23142197
TI  - Comparative study of pharmacokinetics and tissue distribution of osthole in rats
      after oral administration of pure osthole and Libanotis buchtormensis
      supercritical extract.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Libanotis buchtormensis is the source of an
      important traditional medicine from Shaanxi province of China used in the
      treatment of many illnesses. Libanotis buchtormensis supercritical extract (LBSE)
      has analgesic, sedative and anti-inflammatory qualities. Osthole is one of the
      major bioactive components of LBSE; it is known for its significant anti-tumor,
      analgesic, and anti-inflammatory properties, it also alleviates hyperglycemia.
      AIM OF THE STUDY: The purpose of the present study was to compare the
      pharmacokinetics and tissue distribution of osthole in Sprague-Dawley (SD) rats
      after oral administration of pure osthole and LBSE. The two preparations were
      administered at the same osthole dose (approximately 130 mg/kg). The results
      should provide some guidance for the clinical applications of Libanotis
      buchtormensis. MATERIALS AND METHODS: Comparative pharmacokinetics and tissue
      distribution of osthole in SD rats after oral administration of pure osthole and
      LBSE were analyzed using reversed-phase high-performance liquid chromatography
      (RP-HPLC). All pharmacokinetic data were analyzed using 3P97 software. Samples of
      blood and internal organs (heart, liver, spleen, lungs and kidney) were collected
      and pretreated according to the experimental schedule. After pretreatment, plasma
      and tissue samples were extracted using ether-ethyl acetate mixture (3:1, v/v).
      The concentration of osthole in the plasma and tissues were determined using the
      RP-HPLC method. RESULTS: The procedure described in this paper shows good
      precision and stability and is suitable for the osthole assays in biological
      samples. We found that the average plasma concentration-time profile of osthole
      after oral administration of osthole and LBSE showed a single peak. There were
      also clear differences between plasma concentrations of osthole after oral
      administration of pure osthole and LBSE. Non-osthole ingredients in LBSE showed
      some pharmacokinetic interactions with osthole and hence decreased its absorption
      levels (p<0.05). Our results show different tissue distribution of osthole in the
      single and composite administration regimens. CONCLUSIONS: This study compares
      the pharmacokinetic characteristics and tissue distribution of osthole in rats
      after oral administration of pure osthole and LBSE; the results might be useful
      in clinical application of this traditional Chinese herbal medicine.

PMID- 23142198
TI  - Network pharmacology-based prediction of the active ingredients and potential
      targets of Chinese herbal Radix Curcumae formula for application to
      cardiovascular disease.
AB  - ETHNOPHARMACOLOGY RELEVANCE: Cardiovascular and cerebrovascular diseases (CCVD),
      an abnormal function of the heart, brain or blood vessels, are the biggest cause
      of deaths worldwide. Traditional Chinese medicine (TCM) holds a great promise for
      preventing such diseases in an integrative and holistic way. However, its systems
      level characterization of drug-target associations is still unknown. METHODS:
      Here, we have constructed a computational approach by combining chemical
      predictors based on chemical structure, chemogenomics data linking compounds with
      pharmacological information, and a system biology functional data analysis and
      network reconstruction method. RESULTS: The pharmacological system generated 58
      bioactive ingredients from the Chinese herbal Radix Curcumae formula, and
      predicted 32 potential targets related to the CCVD. The results indicates that
      Radix Curcumae share the most common targets with Fructus Gardeniae (15), while
      less common targets with Moschus and Borneolum (8 and 1, respectively). Further
      integrated network shows that Radix Curcumae represents the principal component
      for the prevention of CCVD, and other three medicines serve as adjuvant ones to
      assist the effects of the principal component, which together probably display
      synergistic actions. CONCLUSIONS: Our work successfully explains the mechanism of
      efficiency of Radix Curcumae formula for the prevention of CCVD, and meanwhile,
      predicts the potential targets of the Chinese medicines, which facilitates to
      elucidate the compatible mechanism of the complex prescription, i.e., "jun-chen
      zuo-shi", and provides basis for an alternative approach to investigate novel TCM
      formula on the network pharmacology level.

PMID- 23142199
TI  - Hemodynamic directed CPR improves short-term survival from asphyxia-associated
      cardiac arrest.
AB  - AIM: Adequate coronary perfusion pressure (CPP) during cardiopulmonary
      resuscitation (CPR) is essential for establishing return of spontaneous
      circulation. The objective of this study was to compare short-term survival using
      a hemodynamic directed resuscitation strategy versus an absolute depth-guided
      approach in a porcine model of asphyxia-associated cardiac arrest. We
      hypothesized that a hemodynamic directed approach would improve short-term
      survival compared to depth-guided care. METHODS: After 7 min of asphyxia,
      followed by induction of ventricular fibrillation, 19 female 3-month old swine
      (31+/-0.4 kg) were randomized to receive one of three resuscitation strategies:
      (1) hemodynamic directed care (CPP-20): chest compressions (CCs) with depth
      titrated to a target systolic blood pressure of 100 mmHg and titration of
      vasopressors to maintain CPP>20 mmHg; (2) depth 33 mm (D33): target CC depth of
      33 mm with standard American Heart Association (AHA) epinephrine dosing; or (3)
      depth 51 mm (D51): target CC depth of 51 mm with standard AHA epinephrine dosing.
      All animals received manual CPR guided by audiovisual feedback for 10 min before
      first shock. RESULTS: 45-Min survival was higher in the CPP-20 group (6/6)
      compared to D33 (1/7) or D51 (1/6) groups; p=0.002. Coronary perfusion pressures
      were higher in the CPP-20 group compared to D33 (p=0.011) and D51 (p=0.04), and
      in survivors compared to non-survivors (p<0.01). Total number of vasopressor
      doses administered and defibrillation attempts were not different. CONCLUSIONS:
      Hemodynamic directed care targeting CPPs>20 mmHg improves short-term survival in
      an intensive care unit porcine model of asphyxia-associated cardiac arrest.

PMID- 23142200
TI  - Testosterone related good neurologic outcome on the patients with return of
      spontaneous circulation after cardiac arrest: a prospective cohort study.
AB  - AIM: To evaluate the gonadal hormones in patients with return of spontaneous
      circulation (ROSC) after cardiac arrest following prospectively good (cerebral
      performance category [CPC] 1-2) and poor (CPC 3-5) neurologic outcomes. METHODS:
      The patients in an emergency center who had been admitted to the center's
      intensive care unit (ICU) after successful resuscitation following out-of
      hospital cardiac arrest were prospectively identified and evaluated within the
      period from April 2008 to March 2011. The gonadal hormones, including
      progesterone, total estrogen, and testosterone, were measured and analyzed
      following the good and poor neurologic outcomes. RESULTS: A total of 142 patients
      were analyzed in this study. Thirty-nine (27.5%) patients had good neurologic
      outcomes. The gonadal hormones (progesterone, total estrogen, and testosterone)
      had good vs. poor neurologic outcomes of 1.039+/-0.694 vs. 1.000+/-0.892ng/ml,
      107.956+/-13.163 vs. 117.060+/-11.344 pg/ml, and 307.380+/-33.844 vs. 189.020+/
      17.406 ng/dl, respectively. In the multiple logistic-regression analysis, the
      initial shockable rhythm (5.671 odds ratio [OR], 2.307-13.942 95% confidence
      interval [CI]), time from arrest to ROSC (0.957 OR, 0.933-0.982 95% CI), and more
      than 300 ng/dl of testosterone level (3.279 OR, 1.265-8.190 95% CI) were found to
      be related to good neurologic outcome, respectively. CONCLUSION: Higher
      testosterone levels are related to good neurologic outcome at six months after
      admission in patients with spontaneous circulation after cardiac arrest. The
      testosterone levels may be useful prognostic tools for the postcardiac-arrest
      syndrome and could be used for the latter's neuroprotective treatment, but
      additional randomized controlled studies are needed.

PMID- 23142202
TI  - Prospective, randomized, double-blind, vehicle controlled, multicenter phase IIb
      clinical trial of the pore forming protein PRX302 for targeted treatment of
      symptomatic benign prostatic hyperplasia.
AB  - PURPOSE: We conducted a safety and efficacy evaluation of intraprostatic
      injection of PRX302, a modified pore forming protein (proaerolysin) activated by
      prostate specific antigen, as a highly targeted, localized approach to treat
      lower urinary tract symptoms due to benign prostatic hyperplasia. MATERIALS AND
      METHODS: A total of 92 patients with I-PSS (International Prostate Symptom Score)
      15 or greater, peak urine flow 12 ml or less per second and prostate volume 30 to
      100 ml were randomized 2:1 to a single ultrasound guided intraprostatic injection
      of PRX302 vs vehicle (placebo) in this phase IIb double-blind study. Injection
      was 20% of prostate volume and 0.6 MUg PRX302 per gm prostate. Peak urine flow
      was determined by a blinded reviewer. Benign prostatic hyperplasia medications
      were prohibited. The primary data set of efficacy evaluable patients (73) was
      analyzed using last observation carried forward. RESULTS: PRX302 treatment
      resulted in an approximate 9-point reduction in I-PSS and 3 ml per second
      increase in peak urine flow that were statistically significant changes from
      baseline compared to vehicle. Efficacy was sustained for 12 months. Early
      withdrawal for other benign prostatic hyperplasia treatment was more common for
      patients in the vehicle group. Relative to vehicle, PRX302 apparent toxicity was
      mild, transient, and limited to local discomfort/pain and irritative urinary
      symptoms occurring in the first few days, with no effect on erectile function.
      CONCLUSIONS: A single administration of PRX302 as a short, outpatient based
      procedure was well tolerated in patients with lower urinary tract symptoms due to
      benign prostatic hyperplasia. PRX302 produced clinically meaningful and
      statistically significant improvement in patient subjective (I-PSS) and
      quantitative objective (peak urine flow) measures sustained for 12 months. The
      side effect profile is favorable with most effects attributed to the injection
      itself and not related to drug toxicity.

PMID- 23142201
TI  - Differentiation of calcium oxalate monohydrate and calcium oxalate dihydrate
      stones using quantitative morphological information from micro-computerized and
      clinical computerized tomography.
AB  - PURPOSE: We differentiated calcium oxalate monohydrate and calcium oxalate
      dihydrate kidney stones using micro and clinical computerized tomography images.
      MATERIALS AND METHODS: A total of 22 calcium oxalate monohydrate and 15 calcium
      oxalate dihydrate human kidney stones were scanned using a commercial micro
      computerized tomography scanner with a pixel size of 7 to 23 MUm. Under an
      institutional review board approved protocol, image data on 10 calcium oxalate
      monohydrate and 9 calcium oxalate dihydrate stones greater than 5 mm were
      retrieved from a total of 80 patients who underwent clinical dual energy
      computerized tomography for clinical indications and had stones available for
      infrared spectroscopic compositional analysis. Micro and clinical computerized
      tomography images were processed using in-house software, which quantified stone
      surface morphology with curvature based calculations. A shape index was generated
      as a quantitative shape metric to differentiate calcium oxalate monohydrate from
      calcium oxalate dihydrate stones. Statistical tests were used to test the
      performance of the shape index. RESULTS: On micro-computerized tomography images
      the shape index of calcium oxalate monohydrate and calcium oxalate dihydrate
      stones significantly differed (ROC curve AUC 0.92, p <0.0001). At the optimal
      cutoff sensitivity was 0.93 and specificity was 0.91. On clinical computerized
      tomography images a significant morphological difference was also detected (p =
      0.007). AUC, sensitivity and specificity were 0.90, 1 and 0.73, respectively.
      CONCLUSIONS: On micro and clinical computerized tomography images a morphological
      difference was detectable in calcium oxalate monohydrate and calcium oxalate
      dihydrate stones larger than 5 mm. The shape index is a highly promising method
      that can distinguish calcium oxalate monohydrate and calcium oxalate dihydrate
      stones with reasonable accuracy.

PMID- 23142203
TI  - Utility of adding Primovist magnetic resonance imaging to analysis of
      hepatocellular carcinoma by liver dynamic computed tomography.
AB  - BACKGROUND & AIMS: More information is needed on use of Primovist-enhanced
      magnetic resonance imaging (MRI) during initial staging analysis of patients with
      hepatocellular carcinoma (HCC) who are candidates for treatment with liver
      dynamic computed tomography (CT). METHODS: We studied 104 patients who were
      initially diagnosed as Barcelona Clinic Liver Cancer (BCLC) stage 0 or A, without
      any other suspicious intrahepatic lesions, by liver dynamic CT from December 2009
      to May 2012 at Inha University Hospital in Korea. We evaluated whether an
      addition of Primovist-enhanced MRI examination affected determination of BCLC
      stage, compared with liver dynamic CT. RESULTS: On the basis of CT analysis, the
      median tumor size was 2.3 cm, and 98 patients had HCCs that met the Milan
      criteria (94.2%). All 104 patients (100%) had nodular type HCC. Abnormal
      intrahepatic findings were detected by Primovist-enhanced MRI in 41 patients
      (39.4%). Eighteen patients (17.3%) had new HCCs, but 6 patients who were
      initially of BCLC stage A remained at this stage, despite increases in tumor
      numbers. Of the 104 patients, 31 (29.8%) and 73 (70.2%) had BCLC stage 0 and A
      HCC before Primovist-enhanced MRI, respectively, and 26 (25.0%), 71 (68.3%), and
      7 (6.7%) patients had BCLC stages 0, A, and B HCC after Primovist-enhanced MRI,
      respectively. In 12 of the 104 patients (11.5%), BCLC stage changed from 0 to A
      (5/31, 16.1%) or from A to B (7/73, 9.6%). CONCLUSIONS: Primovist-enhanced MRI
      can provide additional information that can lead to the detection of new
      intrahepatic HCC lesions during initial staging analyses of patients with BCLC
      stage 0 or A HCC by liver dynamic CT, despite the absence of other suspicious
      liver lesions.

PMID- 23142205
TI  - Screening colonoscopy: a new frontier for nurse practitioners.

PMID- 23142204
TI  - Multidisciplinary management of patients with cirrhosis: a need for care
      coordination.
AB  - Cirrhosis is a common chronic condition with high rates of morbidity and
      mortality. Optimal medical management involves a multidisciplinary approach, but
      coordination between medical specialties needs to be improved. This clinical
      perspective discusses care coordination interventions that have been successful
      in other disease states and how they could be applied to the management of
      cirrhosis.

PMID- 23142206
TI  - Use of F-18 fluorodeoxyglucose positron emission tomography with dual-phase
      imaging to identify intraductal papillary mucinous neoplasm.
AB  - BACKGROUND & AIMS: We investigated the usefulness of dual-phase F-18
      fluorodeoxyglucose positron emission tomography with computed tomography (FDG
      PET/CT) to differentiate benign from malignant intraductal papillary mucinous
      neoplasms (IPMNs) and to evaluate branch-duct IPMNs. METHODS: We used FDG-PET/CT
      to evaluate IPMNs in 48 consecutive patients who underwent surgical resection
      from May 2004 to March 2012. IPMNs were classified as benign (n = 16) or
      malignant (n = 32) on the basis of histology analysis. The ability of FDG-PET/CT
      to identify branch-duct IPMNs was compared with that of the International
      Consensus Guidelines. RESULTS: The maximum standardized uptake value (SUVmax) was
      higher for early-phase malignant IPMNs than that for benign IPMNs (3.5 +/- 2.2 vs
      1.5 +/- 0.4, P < .001). When the SUVmax cutoff value was set at 2.0, early-phase
      malignant IPMNs were identified with 88% sensitivity, specificity, and accuracy.
      The retention index values for malignant and benign IPMNs were 19.6 +/- 17.8 and 
      2.6 +/- 12.9, respectively. When the SUVmax cutoff was set to 2.0 and the
      retention index value to -10.0, early-phase malignant IPMNs were identified with
      88% sensitivity, 94% specificity, and 90% accuracy. In identification of branch
      duct IPMNs, when the SUVmax cutoff was set to 2.0, the sensitivity, specificity,
      and accuracy values were 79%, 92%, and 84%, respectively. By using a maximum main
      pancreatic duct diameter >=7 mm, the Guidelines identified branch-duct IPMNs with
      greater specificity than FDG-PET/CT. The Guidelines criteria of maximum cyst size
      >=30 mm and the presence of intramural nodules identified branch-duct IPMNs with
      almost equal sensitivity to FDG-PET/CT. CONCLUSIONS: Dual-phase FDG-PET/CT is
      useful for preoperative identification of malignant IPMN and for evaluating
      branch-duct IPMN.

PMID- 23142207
TI  - Long-term outcome of patients with Crohn's disease who respond to azathioprine.
AB  - BACKGROUND & AIMS: Little is known about the long-term outcomes of patients with
      Crohn's disease (CD) who have a complete response to therapy with azathioprine.
      We assessed the long-term effects of azathioprine in responders. METHODS: We
      collected data from the MICISTA registry (a database from the Rothschild and
      Saint-Antoine Hospitals, Paris, France) on consecutive CD patients treated with
      azathioprine from 1987 to 1999 who responded to therapy (steroid-free clinical
      remission at 1 y); they were followed up until 2011 (n = 220; 86 men; median age,
      32 y; median follow-up period, 12.6 y). Data were compared with those from 440
      matched patients with CD who did not receive immunosuppressants during the same
      inclusion period (controls). RESULTS: The cumulative rate of sustained remission
      10 years after treatment with azathioprine was 38%. Among patients exposed to
      azathioprine during a prospective follow-up period (1995-2011, 1936 patient
      years), the percentage of patient-years with active disease (flare or
      complication during the calendar year) was 17.6%. Compared with the control
      group, at baseline, responders were more often active smokers with significantly
      more extensive disease, perianal lesions, and extradigestive manifestations.
      During follow-up evaluation, responders had a significantly reduced risk of
      intestinal surgery (adjusted odds ratio, 0.69; 95% confidence interval, 0.52
      0.91) and perianal surgery (adjusted odds ratio, 0.36; 95% confidence interval,
      0.27-0.46). A significantly higher percentage of responders developed cancers,
      including nonmelanoma skin cancers, compared with controls (9.5% vs 4.1%; P <
      .01). Survival rates after 20 years were 92.8% +/- 2.3% of responders vs 97.9% +/
      0.8% of controls (P = .01). CONCLUSIONS: Based on a study at a single center,
      patients with CD who responded to azathioprine had a smaller proportion of
      patient-years with active disease, and were less likely to be hospitalized or
      undergo intestinal surgery, than patients with CD who did not receive
      immunosuppressants. These benefits, however, could be offset by an increased risk
      of malignancies.

PMID- 23142208
TI  - Effects of smoking and antioxidant micronutrients on risk of colorectal cancer.
AB  - BACKGROUND & AIMS: Antioxidant intake has been reported to increase the risk of
      colorectal cancer (CRC) for smokers, yet reduce the risk for nonsmokers. We
      investigated the association between tobacco smoking and risk of colon or rectal
      cancer, and whether dietary and supplemental intake of the antioxidant vitamins
      A, C, E, beta-carotene, selenium, zinc, and manganese affects the risk of CRC
      among smokers. METHODS: Data on smoking habits and antioxidant intake were
      analyzed for 54,208 participants in the Danish Prospective Diet, Cancer and
      Health Study. Of these participants, 642 were diagnosed with colon cancer and 348
      were diagnosed with rectal cancer. Hazard ratios and 95% confidence intervals
      were estimated using Cox proportional hazard models. Principal components were
      used to analyze intake of combinations of antioxidants. RESULTS: Ever smoking
      increased the risk for CRC (hazard ratio, 1.19; 95% confidence interval, 1.03
      1.37), especially for rectal cancer. Smoking for at least 20 years was associated
      with a 26% increase in risk of CRC, compared with never smokers, and smoking 20 g
      tobacco or more each day was associated with a 30% increase in risk. Smoking for
      more than 30 years, or more than 20 g tobacco each day, was associated with a 48%
      increase in risk of rectal cancer. We did not observe an interaction between
      smoking and antioxidant consumption on risk of CRC. CONCLUSIONS: Tobacco smoking
      increases the risk for CRC. We did not observe that consumption of antioxidant
      micronutrients modulates the effects of smoking on CRC risk.

PMID- 23142209
TI  - Reply: To PMID 22610009.

PMID- 23142210
TI  - Measurement of alcohol craving.
AB  - Despite considerable research activity and application in treatment, the
      construct of craving remains poorly understood. We propose that cravings and
      urges are cognitive-emotional events in time, characterised by frequency,
      duration, intensity and salience. Commonly used measures of alcohol craving are
      reviewed, and their strengths and weaknesses identified. Most measures confound
      craving with behaviours, or with separable cognitive phenomena such as
      expectancies, intentions, or perceived behavioural control. These confounds have
      limited our advances in understanding the determinants and consequences of
      craving. Based on the criteria applied in this review, among the better
      performing multi-item measures are the Penn Alcohol Craving Scale and Obsessive
      subscale of the Obsessive-Compulsive Drinking Scale. Optimal assessment
      strategies are likely to involve daily assessments of peak intensity of cravings,
      desires or urges and of the frequency and duration of craving episodes. Of
      particular interest are measures of intensity at times when individuals are at
      risk of drinking or of other functional impacts from craving.

PMID- 23142211
TI  - Recurrent major depressive disorder: Imbalance of neurokinin (NK)-1 and NK-2
      receptor expression in monocytes.
AB  - Increasing evidence suggests that tachykinins are involved in the control of
      different pathological conditions, including psychiatric disorders. In this study
      we evaluated the expression of NK(1) and NK(2) receptors (NK-1R and NK-2R), as
      well as the effects of substance P (SP) and neurokinin A (NKA), in monocytes
      isolated from 15 healthy subjects and 15 patients with recurrent major depressive
      disorder (RMDD), under stable antidepressant therapy. NK-1R expression in
      monocytes from RMDD patients was significantly decreased as compared to healthy
      subjects, whereas NK-2R expression was markedly increased. Both NK-1R and NK-2R
      expression correlated with HAM-D, but not HAM-A, score. SP, NKA and selective NK
      1R and NK-2R agonists stimulated TNF-alpha release in monocytes of both groups,
      with a significant higher effect observed in RMDD. Moreover they induced NF
      kappaB activation, which was reversed by selective NK-1R and NK-2R antagonists,
      so demonstrating that it was receptor-mediated. The occurrence of a profound
      alteration in NK receptor expression in RMDD is a novel finding that suggests NK
      1R and NK-2R pathways as possible relevant players in major depressive disorder,
      so improving our understanding of the complex pathogenesis of the disease.

PMID- 23142212
TI  - Microbiota of male genital tract: impact on the health of man and his partner.
AB  - This manuscript describes the male genital tract microbiota and the significance
      of it on the host's and his partner's health. Microbiota exists in male lower
      genital tract, mostly in urethra and coronal sulcus while high inter-subject
      variability exists. Differences appear between sexually transmitted disease
      positive and negative men as well as circumcised and uncircumcised men. Upper
      genital tract is generally germ-free, except in case of infections. Prostatitis
      patients have frequently abundant polymicrobial communities in their semen,
      expressed prostatic secretion and/or post-massage urine. Coryneform bacteria have
      ambivalent role in male urogenital tract being frequently commensals but
      sometimes associated with prostatitis and urethritis. Interactions between male
      and female genital tract microbiota are highly likely yet there are very scarce
      studies on the couples' genital tract microbiota. Increase of bacterial vaginosis
      type microbiota and coliforms are the most typical findings in men while the
      adverse effect of male genital tract bacteria on in vitro fertilization and
      pregnancy outcome has also been indicated.

PMID- 23142213
TI  - A qualitative evaluation of a pre-consultation guide intended to promote the
      participation of young people in asthma review consultations.
AB  - OBJECTIVE: Young people's (age range 14-19 years) participation in consultations
      with health professionals can be limited. There has been little research into pre
      consultation support for young people. This study evaluated a pre-consultation
      guide developed to promote young people's participation in asthma review
      consultations. METHODS: A pre-consultation guide was evaluated in qualitative
      exit interviews with 24 young people and 9 primary care nurses in the United
      Kingdom. RESULTS: Young people found the guide to be reassuring and supportive;
      peer written content, particularly example questions, helped to develop
      confidence and an intention to participate. Nurses suggested the guide could be a
      useful tool to aid young people's communication of asthma-related experiences.
      CONCLUSION: Quotations from young people were highlighted as of particular value.
      Self-efficacy can be increased through observing how peers perform. Confidence
      and intention to change behavior are linked with actual behavior change. Future
      research should explore the impact of the pre-consultation guide on increased
      self-efficacy, developing an intention to change behavior and whether this is
      acted upon. PRACTICE IMPLICATIONS: Used as a tool in a consultation may support
      change in practice nurses' consulting style and enable young people's
      participation.

PMID- 23142214
TI  - Do not put all teleosts in one net: focus on the sox2 and pou2 genes.
AB  - The Pou2 and Sox2 proteins are major transcription factors for development and
      cell differentiation. In teleosts, the expression patterns of pou2 or sox2 are
      different between species from distant families, suggesting different regulatory
      mechanisms of gene expression. In this study, we assessed the divergences among
      teleosts, including within closely related species. The pou2 and sox2 gene
      expression patterns were characterised over several developmental stages in a
      cyprinid model, i.e., the goldfish, and the potential regulation sites of these
      genes within teleost conserved regions were localised. During embryonic
      development, differences in the expression patterns between the goldfish and
      other teleosts, including zebrafish, were observed for both genes. The in silico
      analysis of the 5' flanking regions of the pou2 gene showed high conservation
      within teleosts, whereas the sox2 sequence diverged in tetraodontiforms. Certain
      putative cis regulatory elements were common to all teleosts, whereas others were
      found only in cyprinids. The analysis of the DNA methylation patterns of the pou2
      and sox2 upstream sequences revealed that the studied CpG sites remained
      hypomethylated at all stages of embryo development in both genes. In contrast, in
      the adult fin, the studied CpG sites were hypermethylated in pou2 but not in
      sox2, suggesting the existence of methylation-sensitive regions in pou2. Overall,
      although most similarities at the level of the gene regulatory sites were found
      within cyprinids, the expression pattern of pou2 or sox2 during development
      differs between cyprinids species.

PMID- 23142215
TI  - Enzymatic properties and primary structures of two alpha-amylase isozymes from
      the Pacific abalone Haliotis discus hannai.
AB  - Two alpha-amylase (EC 3.2.1.1) isozymes, HdAmy58 and HdAmy82, with approximate
      molecular masses of 58 kDa and 82 kDa, respectively, were isolated from the
      digestive fluid of the Pacific abalone Haliotis discus hannai. Optimal
      temperatures and pHs for HdAmy58 and HdAmy82 were at 30  degrees C and 6.7, and
      30  degrees C and 6.1, respectively. Both enzymes similarly degraded starch,
      glycogen, and maltooligosaccharides larger than maltotriose producing maltose and
      maltotriose as the major degradation products. However, the activity toward
      maltotetraose was appreciably higher in HdAmy82 than HdAmy58. cDNAs encoding
      HdAmy58 and HdAmy82 were cloned and the amino-acid sequences of 511 and 694
      residues for HdAmy58 and HdAmy82, respectively, were deduced. The putative
      catalytic domains of HdAmy58 and HdAmy82 were located in the 17-511th and 19
      500th amino-acid regions, respectively, and they showed approximately 50% amino
      acid identity to each other. These sequences also showed 62-99% amino-acid
      identity to the catalytic domains of known alpha-amylases that belong to
      glycoside-hydrolase-family 13. The difference in the molecular masses between
      HdAmy58 and HdAmy82 was ascribed to the extension of approximately 190 residues
      in the C-terminus of HdAmy82. This extended region showed 41-63% amino-acid
      identity with the ancillary domains of several alpha-amylases previously
      reported.

PMID- 23142216
TI  - White shrimp Litopenaeus vannamei catalase: gene structure, expression and
      activity under hypoxia and reoxygenation.
AB  - Catalase (EC 1.11.1.6) is an antioxidant enzyme involved in redox equilibrium,
      regulating hydrogen peroxide (H(2)O(2)) concentration, a harmful reactive oxygen
      species (ROS) that is produced during hypoxia. Hypoxia occurs commonly in aquatic
      environments and in shrimp farms. We studied the catalase gene of the shrimp
      Litopenaeus vannamei and tested its expression and enzyme activity during hypoxia
      (1.5mg/L O(2); 6 and 24h) and reoxygenation (1h after hypoxia). The complete gene
      is 2974bp long and has four introns of 821, 223, 114 and 298bp, respectively. The
      first intron has tree microsatellites, with GT and (T)AT(GT) repeated sequences.
      L. vannamei catalase is part of an invertebrate clade including crustaceans and
      rotifers. Catalase expression and activity is different in gills and
      hepatopancreas. Expression in gills increased 3.2 and 3-fold in response to
      hypoxia and reoxygenation (6 and 24h hypoxia, followed by 1h reoxygenation)
      compared to normoxia, while no differences were detected in the expression and
      activity in hepatopancreas. Catalase activity in gills had a contrary response to
      expression in hypoxia and reoxygenation.

PMID- 23142217
TI  - MiR-15b and miR-152 reduce glioma cell invasion and angiogenesis via NRP-2 and
      MMP-3.
AB  - We tested invasion and angiogenesis related mRNA expression and miRNA profiles of
      glioma. Genes with mRNA expression that changed significantly were selected to
      predict possible miRNAs that regulate mRNA expression, and were then matched with
      miRNA results. NRP-2 with the matching miRNA miR-15b, and MMP-3 with the matching
      miRNA miR-152 were selected for further study. Luciferase activity assay
      confirmed that miR-15b and miR-152 attenuate expression of NRP-2 and MMP-3
      protein by binding to NRP-2 and MMP-3 transcript, respectively. In vitro invasion
      assay data showed that miR-15b and miR-152 significantly decreased 9L cell
      invasiveness. In vitro tube formation assay data showed that miR-15b reduced tube
      formation. A preliminary pathway study indicated that miR-15b and miR-152
      deactivated the MEK-ERK pathway via NRP-2 and MMP-3 in 9L cells, respectively.

PMID- 23142218
TI  - MiR-24 regulates the proliferation and invasion of glioma by ST7L via beta
      catenin/Tcf-4 signaling.
AB  - MicroRNAs are strongly implicated as affecting glioma, but their specific roles
      and functions have yet to be fully elucidated. In this study, we defined the
      expression and function of miR-24, which we found to be upregulated in glioma
      samples and glioma cells by qRT-PCR. Downregulation of miR-24 in glioma cell
      lines inhibited proliferation and invasion and induced apoptosis. Using
      computational and expression analysis, ST7L was identified as a candidate target
      of miR-24. A reporter assay with the 3'UTR of ST7L cloned downstream of a
      luciferase gene showed increased luciferase activity in the absence of miR-24,
      providing strong evidence that miR-24 is a direct regulator of ST7L. Furthermore,
      we observed that restoration of ST7L activity resulted in effects that were
      similar to those from transfecting a miR-24 inhibitor into glioma cells.
      Mechanistic investigation revealed that the deletion of miR-24 suppressed beta
      catenin/Tcf-4 transcription activity by targeting ST7L. In conclusion, our study
      demonstrates that miR-24 upregulation is common in glioma and that suppression of
      miR-24 expression inhibits cell proliferation and invasion, suggesting that miR
      24 may act as an oncogene in glioma.

PMID- 23142219
TI  - Down-regulation of miR-517a and miR-517c promotes proliferation of hepatocellular
      carcinoma cells via targeting Pyk2.
AB  - Growing evidence indicates that some tumor suppressive miRNAs are subject to
      epigenetic modifications during carcinogenesis. Here, we found that a large miRNA
      cluster of C19MC was upregulated in HCC cells after combined treatment with DNA
      methylation inhibitor and histone deacetylase inhibitor. MiR-517a and miR-517c
      were strikingly different from the remaining 41 miRNAs in C19MC. Ectopic
      expression of MiR-517a and miR-517c inhibited cell proliferation by blocking G2/M
      transition, whereas down-regulation of miR-517a and miR-517c facilitated cell
      growth. We further showed Pyk2 is a target of miR-517a and miR-517c and both the
      miRNAs are downregulated in HCC samples. These data collectively suggest that
      down-regulation of both miR-517a and miR-517c contribute to HCC development
      through regulating Pyk2.

PMID- 23142220
TI  - Thalidomide maintenance therapy maturates the T cell compartment and compromises
      antigen-specific antitumor immunity in patients with multiple myeloma.
AB  - Interferon (INF)-alpha was the maintenance treatment of choice after autologous
      stem cell transplantation in multiple myeloma in the past, but currently
      Thalidomide is commonly used. In this prospective study, the implications of the
      various types of maintenance therapy on the patients T cell pattern and
      activation status were assessed. T cells were analyzed for expression of surface
      molecules, cytokine secretion, the presence of regulatory T cells, and the
      specific activation against the multiple myeloma antigen HM1.24. T cells from 69
      multiple myeloma patients were analyzed: 19 patients were treated with IFN-alpha;
      26 were treated with Thalidomide; and 24 patients received no maintenance
      therapy. Specific T cell activation with an immunogenic HLA-A2(+)-restricted
      peptide from the myeloma-associated antigen HM1.24 was impaired in the
      Thalidomide group. In accordance with this observation, there was a trend toward
      a higher amount of regulatory T cells in the Thalidomide group. Furthermore,
      patients treated with IFN-alpha showed high rates of naive T cells, whereas a
      high rate of effector memory T cells was observed in the Thalidomide group.
      Importantly, after cessation of Thalidomide therapy, this effect was reversible
      in the CD8 compartment. In conclusion, Thalidomide maintenance therapy has
      profound implications on T cell pattern and activation status, which compromise
      antigen specific antitumor immunity.

PMID- 23142221
TI  - Gene therapy in B-NHL cell line using adenovirus-mediated transfer of secretable
      trimeric TRAIL gene expression driven by CD20 promoter.
AB  - CD20 is a crucial target to B-non-Hodgkin lymphoma (NHL), in fact, a humanized
      anti-CD20 monoclonal antibody, rituximab, is widely applied in clinical practice.
      However, resistance to rituximab often occurs in B-NHL patients, which has
      encouraged us to find new medications to treat B-NHL. In this study, we designed
      a gene therapy strategy targeting CD20 at a transcriptional level mediated by
      adenovirus, in which the stTRAIL gene was driven by a specific CD20 promoter
      fragment. We cloned the CD20 promoter from genome DNA of BJAB cell, a CD20
      positive cell line, and identified its specific transcriptional activity with a
      dual-luciferase reporter assay system. Meanwhile, we constructed the stTRAIL gene
      sequence, which contained secretion signal, isoleucine zipper, and soluble TRAIL
      gene sequence, in which the isoleucine zipper facilitated the product of this
      gene sequence to form a functional homotrimer. The recombinant adenovirus was
      termed as AdP20-stTRAIL, which carried on the fused gene of the CD20 promoter
      fragment and the stTRAIL gene. Our studies confirmed that the stTRAIL could be
      expressed and secreted from BJAB cells infected with AdP20-stTRAIL specifically,
      and it inhibited the growth of these infected BJAB cells in vitro and in vivo.
      Our results indicate that the gene therapy using stTRAIL gene driven by a CD20
      promoter may be an effective strategy in B-NHL treatment.

PMID- 23142222
TI  - Comparative evaluation of a triplex nucleic acid test for detection of HBV DNA,
      HCV RNA, and HIV-1 RNA, with the Procleix Tigris System.
AB  - Nucleic acid testing (NAT) is valuable for screening blood donors for occult
      hepatitis B virus (HBV) infection and infection during the window period in
      countries where HBV is endemic, such as China. An "in-house" NAT (Triplex NAT)
      was developed for screening for HBV DNA, hepatitis C virus (HCV) RNA, and the
      human immunodeficiency virus type 1 (HIV-1) RNA. Using the Triplex NAT, a head-to
      head comparative clinical evaluation was carried out against the most common
      commercial NAT used for blood screening in China: the Procleix Tigris System. A
      total of 33,025 specimens which were negative for Hepatitis B surface antigen,
      HCV antibody and HIV-1 antibody/antigen from potential blood donors were tested
      for HBV DNA, HCV RNA, and HIV-1 RNA by both the in-house Triplex assay and the
      commercially available Procleix Tigris System. Eleven specimens were detected as
      HBV positive by both NATs. Twelve specimens were detected as HBV positive by the
      Procleix Ultrio assay and the discriminatory assays, and not the Triplex. Twenty
      eight specimens were detected as HBV positive by the Triplex and not the Procleix
      Ultrio. This study, combined with other data obtained in China, suggest that at
      least 50% HBV surface antigen negative but DNA-positive blood donations would be
      undetected using the current commercial NATs because of their insufficient
      sensitivity and/or Mini-Pool formatting strategies.

PMID- 23142223
TI  - Decoding brain states using backward edge elimination and graph kernels in fMRI
      connectivity networks.
AB  - In the current study, we present a new approach for decoding brain states based
      on the connectivity graphs extracted from functional magnetic resonance imaging
      (fMRI) data. fMRI connectivity graphs are constructed in different brain states
      and fed into an iterative support vector classifier that is enriched by shortest
      path kernel. The classifier prunes the graphs of insignificant edges via a
      backward edge elimination procedure. The iteration in which maximum
      classification performance occurs is considered as optimum iteration. The edges
      and nodes that survive in the optimum iteration form discriminant networks
      between states. We apply "one-versus-one" approach to extend the proposed method
      into a multi-class classifier. This classifier is used to distinguish between
      five cognitive brain states from a blocked design fMRI data: (1) fixation, (2)
      detection of a single stimulus, (3) perceptual matching, (4) attentional cueing,
      and (5) delayed match-to-sample. The proposed method results in multi-class
      classification accuracy of 86.32%. Posterior cingulate cortex is identified as a
      hub in the networks that separate fixation from tasks. Superior parietal lob has
      the same role to distinguish between different tasks. Connectivity between right
      retrosplential and superior parietal lobe contributes to discrimination in the
      fixation-task and task-task cases.

PMID- 23142224
TI  - High-resolution PLA-based composite scaffolds via 3-D printing technology.
AB  - Fabrication of new biodegradable scaffolds that guide and stimulate tissue
      regeneration is still a major issue in tissue engineering approaches. Scaffolds
      that possess adequate biodegradability, pore size, interconnectivity, bioactivity
      and mechanical properties in accordance with the injured tissue are required.
      This work aimed to develop and characterize three-dimensional (3-D) scaffolds
      that fulfill the aforementioned requirements. For this, a nozzle-based rapid
      prototyping system was used to combine polylactic acid and a bioactive CaP glass
      to fabricate 3-D biodegradable scaffolds with two patterns (orthogonal and
      displaced double layer). Scanning electron microscopy and micro-computer
      tomography showed that 3-D scaffolds had completely interconnected porosity,
      uniform distribution of the glass particles, and a controlled and repetitive
      architecture. Surface properties were also assessed, showing that the
      incorporation of glass particles increased both the roughness and the
      hydrophilicity of the scaffolds. Mechanical tests indicated that compression
      strength is dependent on the scaffold geometry and the presence of glass.
      Preliminary cell response was studied with primary mesenchymal stem cells (MSC)
      and revealed that CaP glass improved cell adhesion. Overall, the results showed
      the suitability of the technique/materials combination to develop 3-D porous
      scaffolds and their initial biocompatibility, both being valuable characteristics
      for tissue engineering applications.

PMID- 23142225
TI  - Elevated chemokine CC-motif receptor-like 2 (CCRL2) promotes cell migration and
      invasion in glioblastoma.
AB  - Chemokine CC-motif receptor-like 2 (CCRL2) is a 7-transmembrane G protein-coupled
      receptor which plays a key role in lung dendritic cell trafficking to peripheral
      lymph nodes. The function and expression of CCRL2 in cancer is not understood at
      present. Here we report that CCRL2 expression level is elevated in human glioma
      patient samples and cell lines. The magnitude of increase is positively
      associated with increasing tumor grade, with the highest level observed in grade
      IV glioblastoma. By gain-of-function and loss-of-function studies, we further
      showed that CCRL2 did not regulate the growth of human glioblatoma U87 and U373
      cells. Importantly, we demonstrated that over-expression of CCRL2 significantly
      enhanced the migration rate and invasiveness of the glioblastoma cells. Taken
      together, these results suggest for the first time that elevated CCRL2 in glioma
      promotes cell migration and invasion. The potential roles of CCRL2 as a novel
      therapeutic target and biomarker warrant further investigations.

PMID- 23142226
TI  - STEAP1 is overexpressed in cancers: a promising therapeutic target.
AB  - The six-transmembrane epithelial antigen of prostate (STEAP) protein was
      identified in advanced prostate cancer and is up-regulated in multiple cancer
      cell lines, including prostate, bladder, colon, ovarian, and Ewing sarcoma.
      STEAP1 was described as a suitable antigen for T-cell-based or antibody-based
      immunotherapy. We have investigated the expression of STEAP1 in 40 human tumor
      types - brain, epithelial, lymphoid - and in their normal tissue counterparts
      using publicly available gene expression data, including the Oncomine Cancer
      Microarray database. STEAP1 was found significantly overexpressed in 11 cancers.
      In addition, high STEAP1 expression was associated with poor overall survival in
      colorectal cancer, diffuse large B cell lymphoma, acute myeloid leukemia and
      multiple myeloma. Taken together, these data suggest that STEAP1 is a potential
      therapeutic target for T-cell based immunotherapy or antibody therapy in a large
      panel of cancers.

PMID- 23142227
TI  - Atypical heat shock response and acquisition of thermotolerance in P388D1 cells.
AB  - Reports of atypical heat shock response in some tumour cell lines emphasize the
      possibilities of alternate stress response mechanisms. We demonstrate here that
      P388D1, a mouse macrophage tumour cell line, failed to induce heat shock proteins
      (HSPs) in response to either heat stress (42  degrees C, 1h) or to heavy metal
      stress induced by arsenic trioxide (5-20 MUM). Heat shock transcriptional factor
      1 (HSF1) that mediates transcriptional up regulation of HSPs during stress was
      found to be deficient in transactivation despite its binding to the promoter
      region of HSP genes. Interestingly, cells exhibited thermotolerance in the
      absence of induced HSPs. However, the tolerance was abrogated in cells treated
      with cycloheximide (250 ng/ml) suggested that thermotolerance was dependent on de
      novo protein synthesis.

PMID- 23142228
TI  - Hippocalcin mediates calcium-dependent translocation of brain-type creatine
      kinase (BB-CK) in hippocampal neurons.
AB  - Hippocalcin (Hpca) is a Ca(2+)-binding protein that is expressed in neurons and
      contributes to neuronal plasticity. We purified a 48 kDa Hpca-associated protein
      from rat brain and identified it to be the creatine kinase B (CKB) subunit, which
      constitutes brain-type creatine kinase (BB-CK). Hpca specifically bound to CKB in
      a Ca(2+)-dependent manner, but not to the muscle-type creatine kinase M subunit.
      The N-terminal region of Hpca was required for binding to CKB. Hpca mediated
      Ca(2+)-dependent partial translocation of CKB (approximately 10-15% of total
      creatine kinase activity) to membranes. N-myristoylation of Hpca was critical for
      membrane translocation, but not for binding to CKB. In cultured hippocampal
      neurons, ionomycin treatment led to colocalization of Hpca and CKB adjacent to
      the plasma membrane. These results indicate that Hpca associates with BB-CK and
      that together they translocate to membrane compartments in a Ca(2+)-dependent
      manner.

PMID- 23142229
TI  - The high immunogenicity induced by modified sporozoites' malarial peptides
      depends on their phi (phi) and psi (psi) angles.
AB  - The importance of CSP- and STARP-derived phi and psi dihedral angles in mHABP
      structure was analysed by (1)H NMR in the search for molecules which can be
      included as components of a first-line-of-defence Plasmodium falciparum
      sporozoite multi-epitope vaccine against the most lethal form of human malaria.
      Most of the aforementioned dihedral angles were left-hand-like polyproline type
      II (PPII(L)) structures whilst others had right-hand-like alpha-helix (alpha(R)),
      thus allowing mHABPS to fit better into MHCII molecules and thereby form an
      appropriate pMHCII complex and also establish the H-bonds which stabilise such
      complex and by this means induce an appropriate immune response. This information
      has great implications for vaccine development, malaria being one of them.

PMID- 23142230
TI  - Hyperoxia-induced ciliary loss and oxidative damage in an in vitro bovine model:
      the protective role of antioxidant vitamins E and C.
AB  - Although elevated oxygen fraction is used in intensive care units around the
      world, pathological changes in pulmonary tissue have been shown to occur with
      prolonged exposure to hyperoxia. In this work a bovine bronchus culture model has
      been successfully used to evaluate the effects of hyperoxia on ciliated
      epithelium in vitro. Samples were cultured using an air interface method and
      exposed to normoxia, 21% O(2) or hyperoxia, 95% O(2). Cilial coverage was
      assessed using scanning electron microscopy (SEM). Tissue damage (lactate
      dehydrogenase, LDH, in the medium), lipid peroxidation (thiobarbituric acid
      reactive substances, TBARS), DNA damage (comet assay), protein oxidation (OxyBlot
      kit) and antioxidant status (total glutathione) were used to assess whether the
      hyperoxia caused significant oxidative stress. Hyperoxia caused a time-dependent
      decline (t(1/2)=3.4d compared to 37.1d under normoxia) in cilial coverage
      (P<0.0001). This was associated with a significant increase in the number of
      cells (2.80 +/- 0.27 * 10(6) compared to 1.97 +/- 0.23 * 10(6)ml(-1) after 6d),
      many apparently intact, in the medium (P<0.05); LDH release (1.06 +/- 0.29
      compared to 0.83 +/- 0.36 MUmol min(-1)g(-1) after 6d; P<0.001); lipid
      peroxidation (352 +/- 16 versus 247 +/- 11 MUmol MDA g(-1) for hyperoxia and
      normoxia, respectively); % tail DNA (18.7 +/- 2.2 versus 11.1 +/- 1.5); protein
      carbonyls (P<0.05); and total glutathione (229 +/- 20 MUmol g(-1) versus 189 +/-
      15 MUmol g(-1)). Vitamins E (10(-7)M) and C (10(-6) or 10(-7)M) alone or in
      combination (10(-7)M and 10(-6)M, respectively) had a significant protective
      effect on the hyperoxia-induced reduction in percentage cilial coverage (P<0.05).
      In conclusion, hyperoxia caused damage to cultured bovine bronchial epithelium
      and denudation of cilia. The antioxidant vitamins E and C significantly protected
      against hyperoxia-induced cilia loss.

PMID- 23142231
TI  - Developmental origins of functional dyspepsia-like gastric hypersensitivity in
      rats.
AB  - BACKGROUND & AIMS: Gastric hypersensitivity (GHS) contributes to epigastric pain
      in patients with functional dyspepsia (FD); the etiology and cellular mechanisms
      of this dysfunction remain unknown. We investigated whether inflammatory insult
      to the colons of neonatal rats induced GHS in adult life. METHODS: We used
      cellular, molecular, and in vivo approaches to investigate the mechanisms of GHS
      in adult rats subjected to neonatal colonic insult by intraluminal administration
      of trinitrobenzene sulfonic acid; controls received saline. Six to 8 weeks later,
      rats were evaluated for GHS and tissue was collected for molecular experiments.
      RESULTS: Inflammatory insult to the colon on post-natal day 10 caused an aberrant
      increase of corticosterone on post-natal day 15 and induced GHS in adult life. We
      called these FD-like rats. Inhibition of glucocorticoid receptors after neonatal
      insult blocked the induction of GHS in adult rats. The aberrant increase of
      plasma corticosterone in neonates increased the plasma concentration of
      norepinephrine, nerve growth factor in the gastric fundus muscularis externae,
      brain-derived neurotrophic factor in the thoracic dorsal root ganglia and spinal
      cord, and down-regulated K(v)1.1 messenger RNA in thoracic dorsal root ganglia
      without affecting the expression of K(v)1.4, Na(v)1.8, TrpA1, TrpV1, or P2X3 in
      FD-like rats. Inhibition of glucocorticoid receptors during neonatal insult or
      the inhibition of adrenergic receptors, nerve growth factor, or brain-derived
      neurotrophic factor in FD-like rats suppressed GHS. The intrathecal
      administration of small interfering RNAs against K(v)1.1 increased GHS in naive
      rats. CONCLUSIONS: Inflammatory insult to the colons of rat pups leads to GHS in
      adult life. GHS is caused by altered expression of genes encoding neurotrophins
      and ion channels, and altered activity of the sympathetic nervous system.

PMID- 23142232
TI  - [Humanitarian care of psoriasis in a child].
AB  - We report a case of psoriasis in a 10-year old Afghan boy, who was attended by a
      French military physician. Psoriasis is not uncommon in children, with one third
      of psoriasis beginning in childhood. The patient's treatment was based on
      emollients, topical corticosteroids, and keratolytics. Systemic agents, such as
      acitretin, can also be used. After reviewing the specifics of pediatric
      psoriasis, we discuss the problem of chronic diseases in humanitarian settings.
      The medical supervision of these patients is difficult because of the lack of
      health-care facilities in such areas.

PMID- 23142233
TI  - Hemicraniectomy in the management of space-occupying ischemic stroke.
AB  - A space-occupying mass effect is a common finding in several stroke subtypes. A
      large, intracranial mass is a potentially life-threatening complication,
      irrespective of its underlying origin, with transtentorial or transforaminal
      herniation being the common endpoint and often the cause of death. Prompt and
      adequate intervention is therefore required. Although sufficient data on the
      management of large haematomas are lacking, there is good evidence from
      randomized trials that in younger patients with life-threatening, space
      occupying, so-called "malignant" middle cerebral artery (MCA) infarctions, early
      hemicraniectomy decreases mortality without increasing the number of severely
      disabled survivors. Yet many questions concerning hemicraniectomy in malignant
      MCA infarction remain open: the definition of a malignant MCA infarct within the
      first hours, optimal timing of surgery, quality of life and acceptance of
      remaining disability, the role of aphasia in patients with dominant hemispheric
      infarcts, the effect of age, and the influence of the pre-morbid status on
      decision making. The joint efforts of neurologists, neurosurgeons, intensive care
      physicians, and rehabilitation physicians are needed to design and conduct
      studies that might answer these questions.

PMID- 23142235
TI  - Practising for progression into nursing: a collaborative approach to the
      preparation of potential nursing students.
AB  - A collaborative project was undertaken between the Clinical Skills Laboratory at
      the Faculty of Health and Social Care Sciences (FHSCS) at Kingston University/St
      George's University of London (KU/SGUL) and Kingston Borough Schools Vocational
      Development Service. The project was designed to address the challenge of
      preparing potential health care students to make informed decisions about a
      career in health care through the development of a strong interface between the
      FHSCS and local schools and colleges. School students were invited to attend
      sessions in the clinical skills/simulation laboratory working alongside student
      nurses to learn fundamental nursing skills. An evaluative study undertaken into
      the project showed that the experience in the simulation laboratory was viewed
      very positively by students and helped them to learn new skills as well as to
      make or affirm positive career choices for nursing. Of the 30 school students
      participating in this study, 12 applied for and were accepted into the pre
      registration nursing programme at this university. 

PMID- 23142234
TI  - The role of aquaporin-4 antibodies in Chinese patients with neuromyelitis optica.
AB  - We determined the presence of aquaporin-4 (AQP4) antibodies by indirect
      immunofluorescence in human AQP4-transfected cells, and evaluated the diagnostic
      and prognostic relevance of AQP4 antibodies in 210 Chinese patients with
      neuromyelitis optica (NMO), high-risk NMO (HR-NMO), classic multiple sclerosis
      (MS), and other neurologic diseases. Patients were enrolled from The General
      Hospital of the Chinese People's Liberation Army and followed-up for a median of
      2 years. The patients with HR-NMO had optico-spinal MS (OSMS; n=3),
      longitudinally extensive transverse myelitis (TM) (n=35), recurrent optic
      neuritis (ON) (n=2), ON with Sjogren's syndrome (n=1) and TM positive for Sjogren
      A(SSA) antibody (n=1). The sensitivity and specificity of AQP4 antibodies in NMO
      were 70.9% and 91%, respectively. The median AQP4 antibody titer was
      significantly higher in patients with NMO (1:320) than in those with HR-NMO
      (1:100) and MS (1:50). Relapse of ON or TM was more likely in patients with AQP4
      seropositive, than AQP4 seronegative, HR-NMO. Among AQP4 seropositive patients,
      66.7% (36/55) had severe ON, 75.9% (41/55) had TM, and 55.6% (30/55) had spinal
      cord lesions longer than three segments, and there were relapses in eight of 55
      patients with ON (14.8%) and 19 of 55 patients with TM (35.2%) during the 2-year
      follow-up. In conclusion, our study reveals that AQP4 antibody is a sensitive and
      specific biomarker for discrimination of NMO, classic MS, and other neurological
      diseases, and is particularly useful for the diagnosis of HR-NMO. AQP4 antibody
      positive patients showed higher frequencies of relapse of ON or TM compared with
      AQP4 antibody-negative patients.

PMID- 23142236
TI  - Could introducing vacuum delivery into the education curriculum of community
      midwives in Yemen improve maternal and neonatal mortality and morbidity outcomes?
AB  - At present in Yemen the neonatal mortality rate stands at 12%. A contributing
      factor is that when abnormalities arise during labour in rural areas, there is an
      absence of trained medical staff to manage complications. Consequently,
      childbearing women are expected to travel long distances to hospitals to receive
      Essential Obstetric Care (EOC). This paper presents a debate over whether vacuum
      delivery should be introduced into the education curriculum of community
      midwifery courses in Yemen. It is proposed that this fundamental change to both
      the educational system and the community midwives role could facilitate a
      reduction in maternal and neonatal mortality and morbidity figures in Yemen.

PMID- 23142237
TI  - Assisting nurses to facilitate student and new graduate learning in practice
      settings: what 'support' do nurses at the bedside need?
AB  - The behaviours of nurses in the community of practice that new graduates and
      students participate directly contribute to learning. These behaviours are
      becoming more important with increasing numbers of students and graduates
      learning in health care contexts. Nurses, whether they assume the role of
      preceptor, buddy or mentor are pivotal in identifying appropriate learning
      opportunities for students and graduates, and assimilating these learners into
      the team. As nurses at the bedside have a designated caseload they need to be
      supported to perform this important role while delivering health care. The
      literature reports a number of constraints for nurses when facilitating the
      learning of others, namely, inadequate preparation about how to foster learning
      in this context, poor planning at the ward level, lack of reward or recognition
      for the role, lack of understanding about the specific learning needs of students
      and new graduates. This discussion paper provides direction for leadership and
      management teams to effectively support nurses who assume the role of preceptor,
      buddy or mentor to assist others' learning in the workplace. The recommendations
      suggest management teams provide for adequate preparation of nurses, effective
      planning of workload and organisation of work in the clinical area, and
      mechanisms for timely and specific feedback to maintain nurses interest and
      motivation in performing the role. Furthermore, senior leadership personnel need
      to establish a culture where the value of teaching and learning in practice is
      recognised and fostered by the entire team.

PMID- 23142238
TI  - Cell adhesion molecule 1 is a new osteoblastic cell adhesion molecule and a
      diagnostic marker for osteosarcoma.
AB  - AIMS: An immunohistochemical screen for mouse embryos showed that cell adhesion
      molecule 1 (CADM1), which is an immunoglobulin superfamily member, was expressed
      in developing bones. Here, we determined the cell types expressing CADM1 and
      examined its usefulness in the differential diagnosis of osteosarcoma. MAIN
      METHODS: Serial sections of murine developing mandibles were stained with anti
      CADM1 antibody, by a coloring substrate reactive to alkaline phosphatase (ALP), a
      broad osteoblastic marker for preosteoblasts to osteoblasts, and by in situ
      hybridization for osteopontin (OPN), a marker for mature osteoblasts. CADM1
      immunohistochemistry was also performed on human remodeling bones, osteosarcomas
      and other soft tissue tumors. KEY FINDINGS: CADM1 immunohistochemistry for the
      mandible revealed that morphologically identifiable osteoblasts expressed CADM1
      on their plasma membranes, but neither osteocytes nor bone lining cells did. At
      the mandibular margin, not only OPN-positive cells but also OPN-negative, ALP
      positive cells were CADM1-positive, whereas inside the mandible, OPN-positive
      cells were often CADM1-negative. Clear membranous staining was detected in the
      majority of osteosarcomas (46/57), whereas only 13% (6/46) of the other soft
      tissue tumors were CADM1-positive (P<0.001). SIGNIFICANCE: These results
      indicated that CADM1 was a novel osteoblastic adhesion molecule that is expressed
      transiently during osteoblastic maturation, and a useful diagnostic marker for
      osteosarcoma cells.

PMID- 23142239
TI  - Ontogenic development of cardiomyocytes derived from transgene-free human induced
      pluripotent stem cells and its homology with human heart.
AB  - AIM: Reprogramming of somatic cells utilizing viral free methods provide a
      remarkable method to generate human induced pluripotent stem cells (hiPSCs) for
      regenerative medicine. In this study, we evaluate developmental ontogeny of
      cardiomyocytes following induced differentiation of hiPSCs. MAIN METHODS:
      Fibroblasts were reprogrammed with episomal vectors to generate hiPSC and were
      subsequently differentiated to cardiomyocytes. Ontogenic development of
      cardiomyocytes was studied by real-time PCR. KEY FINDINGS: Human iPSCs derived
      from episomal based vectors maintain classical pluripotency markers, generate
      teratomas and spontaneously differentiate into three germ layers in vitro.
      Cardiomyogenic induction of these hiPSCs efficiently generated cardiomyocytes.
      Ontogenic gene expression studies demonstrated that differentiation of
      cardiomyocytes was initiated by increased expression of mesodermal markers,
      followed by early cardiac committed markers, structural and ion channel genes.
      Furthermore, our correlation analysis of gene expression studies with human heart
      demonstrated that pivotal structural genes like cardiac troponin, actinin, myosin
      light chain maintained a high correlation with ion channel genes indicating
      coordinated activation of cardiac transcriptional machinery. Finally,
      microelectrode recordings show that these cardiomyocytes could respond aptly to
      pharmacologically active drugs. Cardiomyocytes showed a chronotropic response to
      isoproterenol, reduced Na(+) influx with quinidine, prolongation of beating rate
      corrected field potential duration (cFPD) with E-4031 and reduced beating
      frequency and shortened cFPD with verapamil. SIGNIFICANCE: Our study shows that
      viral free hiPSCs efficiently differentiate into cardiomyocytes with cardiac
      specific molecular, structural, and functional properties that recapitulate
      developmental ontogeny of cardiogenesis. These results, coupled with the
      potential to generate patient-specific hiPSC lines hold great promise for the
      development of in vitro platform for drug pharmacogenomics; disease modeling and
      regenerative medicine.

PMID- 23142240
TI  - Fenofibrate reduces cardiac remodeling and improves cardiac function in a rat
      model of severe left ventricle volume overload.
AB  - AIMS: Fenofibrate is a peroxisome proliferator-associated receptor alpha agonist
      (PPARalpha) used clinically for the management of dyslipidemia and is a
      myocardial fatty acid oxidation stimulator. It has also been shown to have
      cardiac anti-hypertrophic properties but the effects of fenofibrate on the
      development of eccentric LVH and ventricular function in chronic left ventricular
      (LV) volume overload (VO) are unknown. This study was therefore designed to
      explore the effects of fenofibrate treatment in a VO rat model caused by severe
      aortic valve regurgitation (AR) with a focus on cardiac remodeling and myocardial
      metabolism. MAIN METHODS: Male Wistar rats were divided in four groups (13-15
      animals/group): Shams (S) treated with fenofibrate (F; 100 mg/kg/d PO) or not (C)
      and severe AR receiving or not fenofibrate. Treatment was started one week before
      surgery and the animals were sacrificed 9 weeks later. KEY FINDINGS: AR rats
      developed severe LVH (increased LV weight) during the course of the protocol.
      Fenofibrate did not reduce LV weight. However, eccentric LV remodeling was
      strongly reduced by fenofibrate in AR animals. Fractional shortening was
      significantly less affected in ARF compared to ARC group. Fenofibrate also
      increased the myocardial enzymatic activity of enzymes associated with fatty acid
      oxidation while inhibiting glycolytic enzyme phosphofructokinase. SIGNIFICANCE:
      Fenofibrate decreased LV eccentric remodeling associated with severe VO and
      helped maintain systolic function. Studies with a longer follow-up will be needed
      to assess the long-term effects of fenofibrate in chronic volume overload caused
      by aortic regurgitation.

PMID- 23142241
TI  - Wogonin induces apoptosis in RPMI 8226, a human myeloma cell line, by
      downregulating phospho-Akt and overexpressing Bax.
AB  - AIMS: Wogonin is one of the major constituents derived from Scutellaria
      Baicalensis, which has been reported to inhibit cell growth and/or induce
      apoptosis in various cancer cell lines. We aim to investigate the anticancer
      effects and associated mechanisms of wogonin on human multiple myeloma cell line
      in vitro. MAIN METHODS: Effects of wogonin on the proliferation, cell cycle
      progression, and apoptosis of human myeloma cells were examined in vitro. The
      proteins associated with the biological effects of wogonin were analyzed by
      immunoblotting and immunocytochemical staining. In addition, the binding mode of
      wogonin within crystal structure of Akt1 protein was also evaluated by molecular
      docking analysis using the CDOCKER algorithm in Discovery Studio. KEY FINDINGS:
      Myeloma cell growth was attenuated by wogonin (70.4-352.0 MUM) in a concentration
      dependent manner. Cell cycle progression analysis and TUNEL assay showed that
      apoptosis was enhanced in wogonin-treated cells. Increased apoptosis was
      accompanied by decreased level of total-PARP, the arisen of PARP cleavage,
      significantly increased level of Bax protein and decreased level of Bcl-2
      protein. Akt activity was suppressed and phosphorylation of Ser 473 residue was
      decreased in the wogonin-treated cells. Molecular docking analysis revealed
      wogonin could be stably docked into the ligand binding domain of Akt1 protein,
      and presented unique features of binding to Akt1, which indicated detailed
      interaction between wogonin and Akt signaling pathway. SIGNIFICANCE: As wogonin
      was effective in vitro in promotion of apoptosis of myeloma cell by Akt
      modulated, Bax and Bcl-2 related intrinsic apoptotic pathway, wogonin may be a
      potential therapeutic agent against multiple myeloma.

PMID- 23142243
TI  - Diabetes induces gender gap on LCAT levels and activity.
AB  - AIM: High density lipoprotein (HDL) decreases in diabetic women more rapidly than
      what is observed in diabetic men. Here we aimed to study serum LCAT levels and
      LCAT activity in men and women with type 2 diabetes (T2DM) as well as healthy
      controls. MAIN METHODS: We measured serum LCAT activity and levels in 40 patients
      with T2DM plus 40 age-sex and body mass index (BMI)-matched controls. The
      correlation between LCAT levels and activity was measured in the studied groups,
      stratified according to gender. KEY FINDINGS: Patients had a lower LCAT activity,
      diastolic blood pressure, fasting blood sugar, triglyceride, low density
      lipoprotein cholesterol and a higher LCAT levels than controls. The lower LCAT
      activity in patients with T2DM was significant after multiple adjustments for
      age, LCAT levels and BMI, using general linear model (67.9 +/- 1.8 vs. 86.5 +/-
      1.8; P<0.001). Women with T2DM had a lower LCAT activity and a higher LCAT and
      HDL levels compared to men. The lower LCAT activity in women remained significant
      after multiple adjustments for age, BMI and LCAT levels; (61.9 +/- 3.1 vs. 74.17
      +/- 3.61; P<0.05). Statin treatment did not have any significant value on the
      results. HDL was not correlated with LCAT levels or activity in any of the
      studied populations. SIGNIFICANCE: We showed that while LCAT activity is
      decreased in patients with T2DM, LCAT levels is increased. Patients with T2DM
      exhibit opposing effects on LCAT activity and LCAT production which is more
      severe in women. Future prospective studies may elucidate the underlying pathways
      for these observations.

PMID- 23142242
TI  - Therapeutic potential of monoacylglycerol lipase inhibitors.
AB  - Marijuana and aspirin have been used for millennia to treat a wide range of
      maladies including pain and inflammation. Both cannabinoids, like marijuana, that
      exert anti-inflammatory action through stimulating cannabinoid receptors, and
      cyclooxygenase (COX) inhibitors, like aspirin, that suppress pro-inflammatory
      eicosanoid production have shown beneficial outcomes in mouse models of
      neurodegenerative diseases and cancer. Both cannabinoids and COX inhibitors,
      however, have untoward effects that discourage their chronic usage, including
      cognitive deficits and gastrointestinal toxicity, respectively. Recent studies
      have uncovered that the serine hydrolase monoacylglycerol lipase (MAGL) links the
      endocannabinoid and eicosanoid systems together through hydrolysis of the
      endocannabinoid 2-arachidonoylglycerol (2-AG) to provide the major arachidonic
      acid (AA) precursor pools for pro-inflammatory eicosanoid synthesis in specific
      tissues. Studies in recent years have shown that MAGL inhibitors elicit anti
      nociceptive, anxiolytic, and anti-emetic responses and attenuate precipitated
      withdrawal symptoms in addiction paradigms through enhancing endocannabinoid
      signaling. MAGL inhibitors have also been shown to exert anti-inflammatory action
      in the brain and protect against neurodegeneration through lowering eicosanoid
      production. In cancer, MAGL inhibitors have been shown to have anti-cancer
      properties not only through modulating the endocannabinoid-eicosanoid network,
      but also by controlling fatty acid release for the synthesis of protumorigenic
      signaling lipids. Thus, MAGL serves as a critical node in simultaneously
      coordinating multiple lipid signaling pathways in both physiological and disease
      contexts. This review will discuss the diverse (patho)physiological roles of MAGL
      and the therapeutic potential of MAGL inhibitors in treating a vast array of
      complex human diseases.

PMID- 23142244
TI  - Postconditioning with far-infrared irradiation increases heme oxygenase-1
      expression and protects against ischemia/reperfusion injury in rat testis.
AB  - AIMS: Studies have shown that heme oxygenase-1 (HO-1) has a protective role in
      the mechanism underlying hypoxic preconditioning. We used a far-infrared
      radiation (FIR) heater to investigate the postconditioning protective role of HO
      1 against ischemia/reperfusion (I/R) injury in rat testis. MAIN METHODS: Forty
      rats were used. Testis ischemia was mimicked by total obstructive clamping of
      testis vessels for 1, 2, or 4 h, and concomitant postconditioning with 30 min FIR
      or heat light during initially 30 min reperfusion. HO-1 expression and apoptosis
      of testis tissues were examined by immunohistochemistry and in situ terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling
      (TUNEL) assay, respectively. HO-1 protein level and caspase-3 activity were
      analyzed by Western blotting. KEY FINDINGS: There was less apoptotic activity in
      rat testis after FIR, as determined by TUNEL assay. Higher HO-1 protein
      expression was observed by immunohistochemistry and Western blotting (p<0.01) in
      testis cells after FIR postconditioning. In contrast, caspase-3 activity was
      significantly higher in heat light groups, as compared with FIR groups (p<0.01).
      SIGNIFICANCE: FIR postconditioning attenuated I/R injury in rat testis by
      inducing HO-1 expression, which might have a protective role in testis apoptosis
      after I/R injury.

PMID- 23142246
TI  - Role of different approaches to the abdominal retroperitoneum for aortic
      lymphadenectomy in patients with gynecological cancers.
AB  - BACKGROUND: Paraaortic lymphadenectomy (PALN) is a standard part of many
      interventions, but currently there are no established care protocols effective in
      preventing gastro-intestinal (GI) symptoms. The aim of our study was to
      retrospectively evaluate patients with gynecologic cancers submitted to PALN, in
      order to evaluate if different approaches to the retroperitoneum could influence
      the radicality of the procedure and the onset of GI complications. METHODS: We
      divided 121 patients with gynecologic tumors submitted to PALN into 3 groups
      according the used right, left or combined left-right approach to the
      retroperitoneum, comparing the groups according the main surgical-pathological
      parameters, such as the number of nodes removed and the incidence and severity of
      GI complications. RESULTS: The mean number of nodes removed did not significantly
      differ between the groups, while the mean number of positive nodes was
      significantly higher in combined approach. 39.8% of our patients experienced GI
      side effects, but those submitted to the combined approach had a significantly
      higher incidence of GI symptoms. CONCLUSIONS: Our data demonstrate that the
      choice of the retroperitoneal approach could be the most important feature for
      the appearance of post-operative GI side effects, even if there is no significant
      difference on the radicality of PALN performed retroperitoneal approach.

PMID- 23142245
TI  - Curcumin ameliorates arterial dysfunction and oxidative stress with aging.
AB  - We tested the hypothesis that curcumin supplementation would reverse arterial
      dysfunction and vascular oxidative stress with aging. Young (Y, 4-6 months) and
      old (O, 26-28 months) male C57BL6/N mice were given normal or curcumin
      supplemented (0.2%) chow for 4 weeks (n=5-10/group/measure). Large elastic artery
      stiffness, assessed by aortic pulse wave velocity (aPWV), was greater in O (448+/
      15 vs. 349+/-15 cm/s) and associated with greater collagen I and advanced
      glycation end-products and less elastin (all P<0.05). In O, curcumin restored
      aPWV (386+/-15 cm/s), collagen I and AGEs (AGEs) to levels not different vs. Y.
      Ex vivo carotid artery acetylcholine (ACh)-induced endothelial-dependent dilation
      (EDD, 79+/-3 vs. 94+/-2%), nitric oxide (NO) bioavailability and protein
      expression of endothelial NO synthase (eNOS) were lower in O (all P<0.05). In O,
      curcumin restored NO-mediated EDD (92+/-2%) to levels of Y. Acute ex vivo
      administration of the superoxide dismutase (SOD) mimetic TEMPOL normalized EDD in
      O control mice (93+/-3%), but had no effect in Y control or O curcumin treated
      animals. O had greater arterial nitrotyrosine abundance, superoxide production
      and NADPH oxidase p67 subunit expression, and lower manganese SOD (all P<0.05),
      all of which were reversed with curcumin. Curcumin had no effects on Y. Curcumin
      supplementation ameliorates age-associated large elastic artery stiffening, NO
      mediated vascular endothelial dysfunction, oxidative stress and increases in
      collagen and AGEs in mice. Curcumin may be a novel therapy for treating arterial
      aging in humans.

PMID- 23142247
TI  - Boolean modeling of biological regulatory networks: a methodology tutorial.
AB  - Given the complexity and interactive nature of biological systems, constructing
      informative and coherent network models of these systems and subsequently
      developing efficient approaches to analyze the assembled networks is of immense
      importance. The integration of network analysis and dynamic modeling enables one
      to investigate the behavior of the underlying system as a whole and to make
      experimentally testable predictions about less-understood aspects of the
      processes involved. In this paper, we present a tutorial on the fundamental steps
      of Boolean modeling of biological regulatory networks. We demonstrate how to
      infer a Boolean network model from the available experimental data, analyze the
      network using graph-theoretical measures, and convert it into a predictive
      dynamic model. For each step, the pitfalls one may encounter and possible ways to
      circumvent them are also discussed. We illustrate these steps on a toy network as
      well as in the context of the Drosophila melanogaster segment polarity gene
      network. 

PMID- 23142248
TI  - Ecdysteroid receptor signaling disruption obstructs blastemal cell proliferation
      during limb regeneration in the fiddler crab, Uca pugilator.
AB  - To study ecdysteroid signaling during limb regeneration, we have applied RNAi
      (dsRNA) mediated silencing to EcR/RXR, the genes encoding the ecdysteroid
      receptor heterodimer, in the fiddler crab Uca pugilator. We injected RNAi into
      the blastemal chamber during early limb regeneration. Silencing was evaluated by
      knockdown in receptor transcript abundance, and disruption was evaluated by
      changes in growth rate and morphology of limb regenerates. q-PCR results
      indicated a 50% drop in transcript abundance 48h post injection in both RNAi
      (dsEcR/dsRXR) injected ipsilateral and uninjected contralateral blastemas in
      experimental animals relative to controls. EcR/RXR transcript levels further
      decreased over time. Several phenotypes were associated with knockdown. The
      experimental blastema failed to develop; microscopic examination of the arrested
      blastema revealed an absence of the cuticular ingrowths characteristic of the
      beginnings of limb segmentation and cell proliferation assays revealed that the
      arrested blastema had few dividing cells. Ecdysteroid levels were also lowered in
      experimental animals; given the bilateral effects of RNAi on limb buds in
      experimental animals, these results suggest RNAi had a systemic effect. Although
      hormone titers in experimental animals rose to comparable control levels during
      the late proecdysial phase of limb regeneration, most experimental crabs failed
      to molt and died. The overall failure to molt indicates that RNAi receptor
      knockdown has long-term effects. The combined effects of receptor knockdown
      indicate that, although circulating ecdysteroid titers are normally low during
      basal limb bud growth, signaling via the ecdysteroid receptor pathway is
      necessary for establishment of blastemal cell proliferation and development in
      the regenerating limbs of U. pugilator.

PMID- 23142249
TI  - Macrophage heterogeneity and cholesterol homeostasis: classically-activated
      macrophages are associated with reduced cholesterol accumulation following
      treatment with oxidized LDL.
AB  - Macrophages are centrally involved during atherosclerosis development and are the
      predominant cell type that accumulates cholesterol in the plaque. Macrophages
      however, are heterogeneous in nature reflecting a variety of microenvironments
      and different phenotypes may be more prone to contribute towards atherosclerosis
      progression. Using primary human monocyte-derived macrophages, we sought to
      evaluate one aspect of atherogenic potential of different macrophage phenotypes
      by determining their propensity to associate with and accumulate oxidized low
      density lipoprotein (oxLDL). Classically-activated macrophages treated
      simultaneously with interferon gamma (IFNgamma) and tumor necrosis factor alpha
      (TNFalpha) associated with less oxLDL and accumulated less cholesterol compared
      to untreated controls. The combined treatment of IFNgamma and TNFalpha reduced
      the mRNA expression of CD36 and the expression of both cell surface CD36 and
      macrophage scavenger receptor 1 (MSR1) protein. Under oxLDL loaded conditions,
      IFNgamma and TNFalpha did not reduce macrophage protein expression of the
      transcription factor peroxisome proliferator-actived receptor gamma (PPARgamma)
      which is known to positively regulate CD36 expression. However, macrophages
      treated with IFNgamma attenuated the ability of the PPARgamma-specific agonist
      rosiglitazone from upregulating cell surface CD36 protein expression. Our results
      demonstrate that the observed reduction of cholesterol accumulation in
      macrophages treated with IFNgamma and TNFalpha following oxLDL treatment was due
      at least in part to reduced cell surface CD36 and MSR1 protein expression.

PMID- 23142250
TI  - Effects of celastrol on human cervical cancer cells as revealed by ion-trap gas
      chromatography-mass spectrometry based metabolic profiling.
AB  - BACKGROUND: Celastrol, a quinine methide triterpene extracted from a Chinese
      medicine (Trypterygium wilfordii Hook F.), has the potential to become an
      anticancer drug with promising prospects. Cell culture metabolomics has been a
      powerful method to study metabolic profiles in cell line after drug treatment,
      which can be used for discovery of drug targets and investigation of drug
      effects. METHODS: We analyzed the metabolic modifications induced by celastrol
      treatment in human cervical cancer cells, using an ion-trap gas chromatography
      mass spectrometry based metabolomics combined with multivariate statistical
      analysis, which allows simultaneous screening of multiple characteristic
      metabolic pathways related to celastrol treatment. Three representative apoptosis
      inducing cytotoxic agents, namely cisplatin, doxorubicin hydrochloride and
      paclitaxel, were selected as positive control drugs to validate reasonableness
      and accuracy of our metabolomic investigation on celastrol. RESULTS: Anti
      proliferation and apoptotic effects of celastrol were demonstrated by CCK-8
      assay, Annexin-V/PI staining method, mitochondrial membrane potential (deltapsim)
      assay and caspase-3 assay. Several significant metabolites involved in energy,
      amino acid and nucleic acid metabolism in HeLa cells induced by celastrol and
      positive drugs were reported. Our method is proved to be effective and robust to
      provide new evidence of pharmacological mechanism of celastrol. CONCLUSIONS: The
      metabolic alterations induced by drug treatment showed the impaired physiological
      activity of HeLa cells, which also indicated anti-proliferative and apoptotic
      effects of celastrol and these positive drugs. GENERAL SIGNIFICANCE: GC/MS-based
      metabolomic approach applied to cell culture could give valuable information on
      the systemic effects of celastrol in vitro and help us to further study its
      anticancer mechanism.

PMID- 23142251
TI  - Susceptibility of monkeypox virus aerosol suspensions in a rotating chamber.
AB  - Viral aerosols can have a major impact on public health and on the dynamics of
      infection. Once aerosolized, viruses are subjected to various stress factors and
      their integrity and potential of infectivity can be altered. Empirical
      characterization is needed in order to predict more accurately the fate of these
      bioaerosols both for short term and long term suspension in the air. Here the
      susceptibility to aerosolization of the monkeypox virus (MPXV), associated with
      emerging zoonotic diseases, was studied using a 10.7 L rotating chamber. This
      chamber was built to fit inside a Class three biological safety cabinet,
      specifically for studying airborne biosafety level three (BSL3) microorganisms.
      Airborne viruses were detected by culture and quantitative polymerase chain
      reaction (qPCR) after up to 90 h of aging. Viral concentrations detected dropped
      by two logs for culture analysis and by one log for qPCR analysis within the
      first 18 h of aging; viral concentrations were stable between 18 and 90 h,
      suggesting a potential for the MPXV to retain infectivity in aerosols for more
      than 90 h. The rotating chamber used in this study maintained viral particles
      airborne successfully for prolonged periods and could be used to study the
      susceptibility of other BSL3 microorganisms.

PMID- 23142252
TI  - Rapid detection and identification of viroids in the genus Coleviroid using a
      universal probe.
AB  - A simple, low-cost hybridization assay using a universal DIG-labeled riboprobe
      for the rapid detection and identification of coleus viroids is presented. An
      octamer of 32-nucleotide sequence derived from the central conserved region (CCR)
      of viroids in the genus Coleviroid was used to develop a universal cRNA probe (8
      central-conserved-region probe, 8CCR probe) for coleus viroids. Dot-blot
      hybridization assays demonstrated that the sensitivity of this probe was similar
      to specific probes for each CbVd, and Northern hybridization results revealed
      that at least four coleus viroids could be distinguished readily and
      simultaneously using the 8CCR probe. Batch detection assay showed that
      hybridization using the 8CCR probe can identify coleus viroids rapidly and
      effectively. This rapid and low-cost molecular hybridization technique is an
      effective way to survey the occurrence of coleus viroids, and has reference for
      the detection of other viroids and possibly viruses.

PMID- 23142253
TI  - Dorsolateral striatum and dorsal hippocampus: a serial contribution to
      acquisition of cue-reward associations in rats.
AB  - In laboratory rodents, procedural and declarative-like memory processes are often
      considered operating in dual, sometimes even competing with each other. There is
      evidence that the initial approach of a repetitive task first engages a
      hippocampus-dependent declarative-like memory system acquiring knowledge. Over
      repetition, there is a gradual shift towards a striatum-dependent response memory
      system. In the current experiment, Long-Evans male rats with bilateral, fiber
      sparing ibotenic acid-induced lesions of the dorsolateral striatum or the dorsal
      hippocampus were trained in an olfactory associative task requiring the
      acquisition of both a procedural and a declarative-like memory. Rats with
      dorsolateral striatum lesions, and thus an intact hippocampus, were impaired on
      both sub-categories of memory performance. Rats with dorsal hippocampal lesions
      exhibited a substantial deficit in learning the declarative-like cue-reward
      associations, while the acquisition of the procedural memory component of the
      task was not affected. These data suggest that the dorsolateral striatum is
      required to acquire the task rule while the dorsal hippocampus is required to
      acquire the association between a given stimulus and its associated outcome. The
      finding is that the dorsolateral striatum and the dorsal hippocampus most
      probably contribute to successful learning of cue-reward associations in a
      sequential (from procedural to declarative-like memory) order using this
      olfactory associative learning task.

PMID- 23142254
TI  - Common bone turnover markers in rheumatoid arthritis and ankylosing spondylitis:
      a literature review.
AB  - We studied the impact of inflammatory rheumatism and its treatment on the most
      common bone turnover markers, based on six previously defined questions in a
      systematic literature review in order to define their place in daily clinical
      practice. The role of bone is currently considered of particular importance
      concerning cartilage damage in inflammatory rheumatism (rheumatoid arthritis and
      ankylosing spondylitis) and the new concept of osteoimmunology has emerged. Some
      bone turnover markers are available in clinical practice. In spite of rich and
      extensive literature on bone turnover markers, their use in inflammatory
      rheumatism or even osteoporosis is not clear, and a systematic literature review
      became necessary. In spite of a large number of different markers used in
      literature, few of them that are useful in common practice have been studied in
      the field of inflammatory rheumatism such as rheumatoid arthritis and ankylosing
      spondylitis. Although their study enables understanding of the physiopathological
      mechanisms of osteoporosis in inflammatory rheumatism, their use in current
      common practice cannot be recommended. Interesting data on the forecast of the
      structural evolution of rheumatoid arthritis has been found within the framework
      of clinical research, without any real practical impact today.

PMID- 23142255
TI  - Temporal arteritis in the young.
AB  - Temporal arteritis in the form of giant cell arteritis (GCA) is common in the
      elderly but is extremely rare in patients less than 50 years of age. We describe
      two male patients: one who presented at the age of 31 years with painful, nodular
      swellings of both temporal arteries and whose temporal artery biopsy demonstrated
      a non-giant cell panarteritis with mixed inflammatory cell infiltrate typical of
      juvenile temporal arteritis (JTA); another one, aged 40 years, who presented with
      headache and cerebral angiography consistent with an intracranial vasculitis and
      whose temporal artery biopsy confirmed an authentic multinucleated GCA. The first
      patient spontaneously improved after biopsy and the second patient has responded
      well to corticosteroid therapy. These two cases exemplify well two distinct but
      extremely rare forms of temporal arteritis in young patients. A 3rd subset is
      that associated with a systemic vasculitis. Few cases of JTA have been reported
      and, to our knowledge, we describe in this report one of the only cases of GCA
      with central nervous system involvement in the young.

PMID- 23142256
TI  - Polyarticular sonographic assessment of gout: a hospital-based cross-sectional
      study.
AB  - OBJECTIVE: To assess the sonographic frequency of synovial effusion, synovial
      hypertrophy, synovitis, and double contour sign at joints commonly affected by
      gout and whether these features differ according to serum urate levels, disease
      duration, and use of urate-lowering therapy. METHODS: Participants with gout were
      recruited from rheumatology clinics. A detailed clinical assessment was
      undertaken of gout history, co-morbidities, medication, alcohol consumption,
      height, weight, clinical synovitis, tophi, and serum urate. Sonographic
      examination of the metatarsophalangeal joints, ankles, knees, metacarpophalangeal
      joints, wrists and elbows for synovial effusion, synovial hypertrophy, synovitis
      and double contour sign was undertaken. The mean number of joints affected were
      compared according to serum urate (<360 MUmol/L versus >=360 MUmol/L), urate
      lowering therapy (yes/no), and disease duration (<=5 years versus>5 years).
      RESULTS: Forty patients participated in the study. Synovial effusion, synovial
      hypertrophy, synovitis, and double contour sign were identified in 36 (90%), 38
      (95%), 24 (62%) and 37 (93%) participants respectively. Synovial effusion was
      seen most frequently at the knee (right 70%, left 68%) followed by the first
      metatarsophalangeal (right 48%, left 40%) and lesser metatarsophalangeal joints
      (right 45%, left 35%). Synovial hypertrophy, synovitis, and double contour sign
      were seen most frequently at the first metatarsophalangeal joint (hypertrophy:
      right 65%, left 60%; synovitis: right 18%, left 18%; double contour: right 60%,
      left 68%). These findings did not differ according to serum urate, disease
      duration, or use of urate-lowering therapy. CONCLUSION: Polyarticular sonography
      frequently identifies synovial effusion, synovial hypertrophy, synovitis and
      double contour sign in patients with gout, particularly at the
      metatarsophalangeal joints and knees.

PMID- 23142257
TI  - Effects of finishing period length with vitamin E supplementation and alfalfa
      grazing on carcass color and the evolution of meat color and the lipid oxidation
      of light lambs.
AB  - Indoor-kept concentrate-fed light lambs (n=54) were supplemented with 500 mg of
      dl-alpha-tocopheryl acetate/kg concentrate for 0, 10, 20 and 30 d before
      slaughtering at 22-24 kg BW. Simultaneously, 8 lambs with their dams were alfalfa
      grazed and the lambs were slaughtered at the same weight. The age at slaughter
      and carcass characteristics were more affected by grazing than by supplementation
      with alpha-tocopherol. The grazing lambs had similar alpha-tocopherol levels to
      the lambs fed concentrate with dl-alpha-tocopheryl acetate for 10 days before
      slaughter. The length of the feeding period affected the evolution of the color,
      delaying the blooming and discoloration of the meat. Feeding lambs alpha
      tocopherol enriched concentrate during the last 10 days of life or grazing them
      on alfalfa drastically diminished the lipid oxidation of the meat. Alfalfa
      grazing is a feasible alternative to increase light lamb meat shelf life without
      using additives.

PMID- 23142258
TI  - BMI as a cofounder or mediator in relation between sugar sweetened beverages and
      type 2 diabetes biomarkers: an overadjustment in cross-sectional study?

PMID- 23142259
TI  - Primary paratesticular neuroblastoma: an important differential diagnosis.
AB  - Primary neuroblastoma as a paratesticular tumor is extremely rare with only 8
      described cases worldwide. In this article, we present the case of a 5-month-old
      boy with this rare tumor location and give an update on the current literature.
      As in our case, typically these tumors present as Stage 1 disease and simple
      tumorectomy alone leads to excellent outcome and long-term survival. However,
      unawareness of this differential diagnosis and misinterpretation of
      intraoperative frozen sections have shown to result in delay of diagnosis and
      worse, overtreatment including orchiectomy and unnecessary chemotherapy.
      Therefore, primary paratesticular neuroblastoma must be considered as a
      differential diagnosis when evaluating and operating children with paratesticular
      tumors.

PMID- 23142260
TI  - Emerging noninvasive biomarkers for early detection of Alzheimer's disease.
AB  - Alzheimer's disease (AD) diagnosis still depends on the triad of clinical,
      imaging and neuropsychological testing. The development of accurate, easy to use
      and inexpensive biological markers for AD is a long-standing aspiration for
      researchers and the medical community. Here we describe some of the recent
      advances in the field of biomarkers, both in cerebrospinal fluid (CSF) and in
      peripheral blood.

PMID- 23142261
TI  - Genetics of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most frequent cause of dementia in the elderly
      and represents an important and increasing clinical challenge in terms of
      diagnosis and treatment. This review highlights the role of genetics in
      understanding the pieces of the complex AD puzzle and summarizes the genes known
      to be involved in Alzheimer's disease. The amount of risk of Alzheimer's disease
      that is attributable to genetics is estimated to be ~70%. Mutations in the genes
      encoding amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2
      (PSEN2) are responsible for early-onset autosomal dominant AD. Although mutations
      in these genes account for ~1% of AD cases, their identification has been crucial
      to understand the molecular mechanisms of AD. For the more common complex late
      onset AD, the E-4 allele of the gene encoding apolipoprotein E (APOE) has been
      recognized as a major genetic risk factor. More recently, several potential
      disease risk genes have been identified with the use of advanced genomic methods
      like genome-wide association studies (GWAS). In the end, the knowledge of the
      pathophysiological mechanisms leading to AD will enable the development of more
      accurate diagnostic tests and new disease-treating strategies.

PMID- 23142262
TI  - Contribution of neuroimaging to the diagnosis of Alzheimer's disease and vascular
      dementia.
AB  - The aim of this study was to review, summarize and analyze recent findings
      relevant to the contribution of neuroimaging to the diagnosis of Alzheimer's
      disease (AD) and vascular dementia (VaD). Computerized tomography (CT) or
      magnetic resonance imaging (MRI) provide accurate demonstration of the location
      and rate of progression of atrophic changes affecting the brain in AD and the
      different types of vascular lesions observed in mixed dementias and in pure VaD.
      Quantification of cortical thickness allows early diagnosis and rate of
      progression from mild cognitive impairment (MCI) to dementia. White matter
      involvement can also be quantified with diffusion tensor imaging (DTI) and
      functional methods including fMRI, functional connectivity, and MR spectroscopy
      (MRS). Isotope-based techniques such as positron emission tomography (PET) allow
      measurement of regional cerebral glucose metabolism using (18)F-2-fluoro-deoxy-D
      glucose (FDG). Cerebral blood flow can be measured using PET with H(2)(15)O or
      with single photon emission computerized tomography (SPECT) with technetium
      ((99m)Tc-HMPAO) or, more recently, arterial spin label (ASL) imaging. There are
      isotope markers for amyloid-beta ((11)O-PIB, (18)F-florbetapir), tau ((18)FDDNP)
      and activated microglia ((11)C-PK11195). Neuroimaging markers are particularly
      useful at the early symptomatic and preclinical asymptomatic phases of AD, as
      well as serving as endpoints in clinical trials.

PMID- 23142264
TI  - Understanding risk factors for Alzheimer's disease: interplay of
      neuroinflammation, connexin-based communication and oxidative stress.
AB  - Alzheimer's disease (AD) is an age-related neurodegenerative disease
      characterized by dementia and the presence of amyloid plaques and anomalous tau
      aggregates. Although pathophysiological mechanisms are still unclear,
      neuroinflammation and glial cell dysfunction have been identified as conspicuous
      components of AD. Glial cell dysfunction is associated with dysregulated
      production of inflammation mediators and generation of both reactive oxygen
      species (ROS) and reactive nitrogen species (RNS), which affect synapses and
      induce neuronal damage. Importantly, both increased neuroinflammation and ROS/RNS
      production by glia dysregulate communication mediated by connexin-based channels
      in brain cells, which could further affect oxidative balance and neuronal
      viability. Recent evidence suggests that connexin-based channels could be
      involved in AD pathogenesis. Here we discuss how aging affects neuroinflammation,
      oxidative stress, and connexin-based channels and the potential relevance of
      these changes for AD. Understanding how they cooperate as pathogenic mechanisms
      of AD is promising for the discovery of new therapeutic strategies against
      neurodegenerative disorders.

PMID- 23142265
TI  - Interleukin-6 polymorphisms are associated with obesity and hyperglycemia in
      Mexican adolescents.
AB  - BACKGROUND AND AIMS: Interleukin-6 is an inflammatory response mediator used as a
      metabolic marker of obesity. Polymorphisms IL6 -597C>A, -572G>C, and -174G>C
      modify the production of this protein. The associations between these haplotypes
      and obesity or metabolic markers have not been studied in adolescents, so an
      analysis of these associations was performed. METHODS: The cross-sectional study
      included 745 apparently healthy 14- to 19-year-old adolescents. Obesity, serum
      glucose, insulin, triglycerides, total cholesterol, low-density lipoprotein
      cholesterol, high-density lipoprotein-cholesterol (HDL-C), and high-sensitivity C
      reactive protein (hs-CRP) were evaluated, and IL6 -597G>A, -572G>C and -174G>C
      polymorphisms determined. The associations were analyzed using multivariate
      logistic regression models. RESULTS: The allele frequencies were 0.15 for -597A
      and -174C and 0.30 for -572C. Genotypes were in Hardy-Weinberg equilibrium. IL-6(
      597/-572/-174) haplotypes GGG, GCG, and AGC comprised 99.74% of the total
      haplotypes. The associations were significant between genotype GCG/GCG and
      hyperglycemia (OR = 2.86, 95% CI = 1.02-7.97); between GCG/GCG and high hs-CRP
      (OR = 6.17, 95% CI = 1.13-33.77); between AGC/AGC and obesity (OR = 4.42, 95% CI
      = 1.40-14.01); and between GGG/GCG and low HDL-C (OR = 1.53, 95% CI = 1.03-2.28).
      CONCLUSIONS: Genotypes of the IL6(-597/-572/-174) polymorphisms are associated
      with metabolic risk factors in Mexican adolescents.

PMID- 23142263
TI  - Deregulated Cdk5 activity is involved in inducing Alzheimer's disease.
AB  - Alzheimer's disease (AD), the most devastating chronic neurodegenerative disease
      in adults, causes dementia and eventually, death of the affected individuals.
      Clinically, AD is characterized as late-onset, age-dependent cognitive decline
      due to loss of neurons in cortex and hippocampus. The pathologic corollary of
      these symptoms is the formation of senile plaques and neurofibrillary tangles.
      Senile plaques are formed due to accumulation of oligomeric amyloid beta (Abeta)
      forming plaques. This occurs due to the amyloidogenic processing of the amyloid
      precursor protein (APP) by various secretases. On the other hand, neurofibrillary
      tangles are formed due to hyperphosphorylation of cytoskeleton proteins like tau
      and neurofilament. Both are hyperphosphorylated by cyclin-dependent kinase-5
      (Cdk5) and are part of the paired helical filament (PHF), an integral part of
      neurofibrillary tangles. Unlike other cyclin-dependent kinases, Cdk5 plays a very
      important role in the neuronal development. Cdk5 gets activated by its neuronal
      activators p35 and p39. Upon stress, p35 and p39 are cleaved by calpain resulting
      in truncated products as p25 and p29. Association of Cdk5/p25 is longer and
      uncontrolled causing aberrant hyperphosphorylation of various substrates of Cdk5
      like APP, tau and neurofilament, leading to neurodegenerative pathology like AD.
      Additionally recent evidence has shown increased levels of p25, Abeta,
      hyperactivity of Cdk5, phosphorylated tau and neurofilament in human AD brains.
      This review briefly describes the above-mentioned aspects of involvement of Cdk5
      in the pathology of AD and at the end summarizes the advances in Cdk5 as a
      therapeutic target.

PMID- 23142266
TI  - Detection of pregnancy and fertility status in big cats using an enzyme
      immunoassay based on 5alpha-pregnan-3alpha-ol-20-one.
AB  - Development of non-invasive steroid hormone assays using fecal samples is crucial
      for detection of pregnancy and monitoring of fertility status in big cats and
      thus facilitates conservation and management of wild animals. Due to changes in
      metabolism and excretory pattern, animals excrete different steroid metabolites
      in feces and urine. The present study is an attempt to develop a common enzyme
      immunoassay for 5alpha-pregnan-3alpha-ol-20-one one of the predominant
      progestogen metabolites in the feces samples of big cats. The developed ELISA
      showed a high sensitivity and low cross reactivity to other hormones compared to
      commercially available RIA kits based on progesterone antibody. It could be used
      in a wide range of animals for monitoring fertility status and pregnancy
      detection by measuring fecal steroid metabolites.

PMID- 23142267
TI  - Non-specific inhibitors of aquaporin-4 stimulate S100B secretion in acute
      hippocampal slices of rats.
AB  - Aquaporin-4 (AQP-4) is the principal brain water channel and is predominantly
      expressed in astrocytes suggesting its dynamic involvement in water homeostasis
      in brain tissue. Due to the co-localization of AQP-4 and inward rectifier K(+)
      channels Kir 4.1, a functional coupling between these proteins has been proposed.
      AQP-4 has a putative role in the physiopathology of brain disorders including
      epilepsy and trauma. S100B is a calcium-binding protein expressed and secreted by
      astrocytes, and commonly used as a parameter of astroglial activation. Here, we
      investigate a possible link between AQP-4 activity (and Kir 4.1) and S100B
      secretion in hippocampal slices of rats of different ages using non-specific
      inhibitors of AQP-4 (AZA, acetazolamide and TEA, tetraethylammonium) and Kir 4.1
      (barium chloride). We found that blockade of AQP-4 with TEA and AZA produced an
      increase in S100B secretion in young rats, compatible with an astroglial
      activation observed in many conditions of brain injury. On the other hand,
      BaCl(2) induced Kir 4.1 inhibition caused a decrease in S100B secretion. Both
      channels, AQP-4 and Kir 4.1, exhibited a similar ontogenetic profile, in spite of
      the functional uncoupling, in relation to S100B secretion. Moreover, we found a
      significant increase in the S100B secretion basal levels with the increasing of
      animal age and the incubation with high levels of potassium resulted in a
      decrease of S100B secretion in 30 and 90-day old rats. These data, together with
      previous observations from gap junctions and glutamate transport of astrocytes,
      contribute to characterize the operational system involving astroglial
      activation, particularly on S100B secretion, in brain disorders.

PMID- 23142268
TI  - Recall versus familiarity when recall fails for words and scenes: the
      differential roles of the hippocampus, perirhinal cortex, and category-specific
      cortical regions.
AB  - This fMRI study examined recall and familiarity for words and scenes using the
      novel recognition without cued recall (RWCR) paradigm. Subjects performed a cued
      recall task in which half of the test cues resembled studied items (and thus were
      familiar) and half did not. Subjects also judged the familiarity of the cue
      itself. RWCR is the finding that, among cues for which recall fails, subjects
      generally rate cues that resemble studied items as more familiar than cues that
      do not. For words, left and right hippocampal activity increased when recall
      succeeded relative to when it failed. When recall failed, right hippocampal
      activity was decreased for familiar relative to unfamiliar cues. In contrast,
      right Prc activity increased for familiar cues for which recall failed relative
      to both familiar cues for which recall succeeded and to unfamiliar cues. For
      scenes, left hippocampal activity increased when recall succeeded relative to
      when it failed but did not differentiate familiar from unfamiliar cues when
      recall failed. In contrast, right Prc activity increased for familiar relative to
      unfamiliar cues when recall failed. Category-specific cortical regions showed
      effects unique to their respective stimulus types: The visual word form area
      (VWFA) showed effects for recall vs. familiarity specific to words, and the
      parahippocampal place area (PPA) showed effects for recall vs. familiarity
      specific to scenes. In both cases, these effects were such that there was
      increased activity occurring during recall relative to when recall failed, and
      decreased activity occurring for familiar relative to unfamiliar cues when recall
      failed.

PMID- 23142269
TI  - Caudal ventrolateral medulla mediates baroreceptor afferent inputs to subfornical
      organ angiotensin II responsive neurons.
AB  - Although anatomical data indicates that the caudal ventrolateral medulla (CVLM)
      projects directly to the subfornical organ (SFO), little is known about the
      afferent information relayed through the CVLM to SFO. Experiments were done in
      the anesthetized rat to investigate whether CVLM neurons mediate baroreceptor
      afferent information to SFO and whether this afferent information alters the
      response of SFO neurons to systemic injections of angiotensin II (ANG II).
      Extracellular single unit recordings were made from 78 spontaneously discharging
      single units in SFO. Of these, 32 (41%) responded to microinjection of L
      glutamate (L-Glu; 0.25M; 10nl) into CVLM (27/32 were inhibited and 5/32 were
      excited). All 32 units also were excited by systemic injections of ANG II
      (250ng/0.1ml, ia). However, only those units inhibited by CVLM (n=27) were found
      to be inhibited by the reflex activation of baroreceptors following systemic
      injections of phenylephrine (2MUg/kg, iv). Activation of CVLM or arterial
      baroreceptors in conjunction with ANG II resulted in an attenuation of the SFO
      unit's response to ANG II. Finally, microinjections (100nl) of the synaptic
      blocker CoCl(2) or the non-specific glutamate receptor antagonist kynurenic acid
      into CVLM attenuated (10/13 units tested) the SFO neuron's response to activation
      of baroreceptors, but not the unit's response evoked by systemic ANG II. Taken
      together, these data suggest that baroreceptor afferent information relayed
      through CVLM functions to modulate of the activity of neurons within SFO to
      extracellular signals of body fluid balance.

PMID- 23142270
TI  - Molecular cytogenetic characterization of 2p23.2p23.3 deletion in a child with
      developmental delay, hypotonia and cryptorchism.
AB  - Deletions of the short arm of chromosome 2 are exceedingly rare and only nine
      cases involving regions from 2p23 to 2pter have been reported to date. Most of
      these deletions had only been analysed by GTG banding. Here, we report an
      interstitial de novo deletion resulting in a microdeletion of 3.9 Mb involving
      2p23.2-p23.3 segment, detected by SNP-array analysis, in a 5 year-old boy showing
      hypotonia, overweight, dysmorphic facial features and cryptorchidism. We compared
      the clinical features of the present case to previously described patients with
      deletions within this chromosomal region. Our case adds new information to the
      deletion of the distal part of chromosome 2p improving the knowledge on this
      rearrangement.

PMID- 23142271
TI  - Acrocallosal syndrome: identification of a novel KIF7 mutation and evidence for
      oligogenic inheritance.
AB  - OBJECTIVE: Acrocallosal syndrome (ACLS) is a rare genetically heterogeneous
      disorder characterised by a variety of developmental anomalies including agenesis
      or hypoplasia of the corpus callosum. ACLS and the related disorder,
      hydrolethalus syndrome, have recently been reported to be caused by mutations in
      the KIF7 gene. In the present study we report a 15 year follow up of a
      consanguineous family with ACLS and the results of exome sequencing. RESULTS: A
      novel in-frame deletion KIF7 mutation (p.218-221del) was detected. This is the
      first deletion mutation in KIF7 described in ACLS and is predicted to disrupt the
      KIF7 protein within the kinesin motor domain. Also present, in addition to the
      homozygous KIF7 mutation, were loss of function variants in known ciliopathy
      genes; AHI1 (p.R830W), BBS2 (p.N70S) and BBS4 (p.M472V). CONCLUSION: KIF7 has
      previously been demonstrated to regulate function of primary cilia and ACLS is
      now categorised as a ciliopathy - a group of disorders in which oligogenic
      disease is frequent. The finding of known loss of function variants in ciliopathy
      associated genes, AHI1, BBS2 and BBS4 in addition to KIF7 mutations provides
      evidence for oligogenic inheritance in ACLS and suggests that this might
      contribute to the phenotypic variability of KIF7-related disorders.

PMID- 23142272
TI  - Epigenetic mechanisms regulating learning and long-term memory.
AB  - A balance between rapid, short lived, neuronal responses and prolonged ones
      fulfill the biochemical and cellular requirements for creating a molecular
      memory. I provide an overview of epigenetic mechanisms in the brain and discuss
      their impact on synaptic plasticity, cognitive functions, and discuss a recent
      example of how they can contribute to neurodegeneration and the cognitive decline
      associated with Alzheimer's disease. 

PMID- 23142273
TI  - In vivo roughening of retrieved total knee arthroplasty femoral components.
AB  - BACKGROUND: Joint registry data highlights the higher rates of cumulative
      revision for younger patients undergoing TKR. One of the reasons associated with
      this higher revision rate may be due to the wear of the UHMWPE leading to
      loosening. Alternate bearing surfaces have been developed to address this
      problem; however, roughening of the metal bearing surface has not been
      demonstrated in vivo. METHOD: We recorded roughness measurements of retrieved
      femoral components. RESULTS: Average lateral condyle roughness was 0.032 MUm,
      compared to control values of 0.020 MUm, p=0.002; average medial condyle
      roughness was 0.028 MUm, compared to a control value of 0.019, p<0.001.
      CONCLUSION: There was a small but statistically significant roughening of femoral
      components in vivo compared to controls. This may have important implications for
      aseptic loosening of knee arthroplasty components and the decision to use scratch
      resistant components.

PMID- 23142274
TI  - The effect of ankle and knee immobilization on postural control during standing.
AB  - BACKGROUND: This study examined the effects of ankle and knee joint
      immobilization on postural control in healthy young adults while standing.
      METHODS: The 24 participants included in this study participated in postural
      standing tests under four different constraint conditions: free joints, ankle
      immobilization only, knee immobilization only, and ankle-knee immobilization.
      Tests were performed using a commercial balancing equipment (Biodex(TM), Inc.,
      NY, USA) and software. RESULTS: The overall limit-of-stability score and duration
      to completion of task were obtained at 75% limit-of-stability (moderate level of
      difficulty). The overall limit-of-stability score of free joints (34.5+/-9.1)
      were significantly different with the ankle immobilization only (26.0+/-11.6),
      and ankle-knee immobilization (26.4+/-7.4) conditions. The test duration
      increased in the following order: free joints (57.8+/-10.9), knee immobilization
      only (62.5+/-14.0), ankle immobilization only (68.0+/-14.9), and ankle-knee
      immobilization (69.4+/-17.7). The duration of the free joint condition greatly
      decreased than ankle immobilization only and ankle-knee immobilization
      conditions. CONCLUSIONS: The ankle and knee joints have sufficient range of
      motion to prevent falls related to decrease postural stability due to
      insufficient range of motion or to improve postural stability.

PMID- 23142275
TI  - ST2 gene-deletion reveals a role of Foxp3+ regulatory T cells in diabetes
      modulation in BALB/c mice.
AB  - BALB/c mice are resistant to diabetes induced by multiple low doses of
      streptozotocin (MLD-STZ; 5 * 40 mg/kg body weight [b.w.]) regimen in contrast to
      C57/BL6 mice. The deletion of ST2 gene renders BALB/c mice susceptible to
      diabetes induction. Cyclophosphamide (CY) in the dose of 175 mg/kg b.w.
      eliminated CD4+Foxp3+ regulatory T cells (Tregs) and enhanced disease severity in
      C57/BL6 mice, but it did not overcome resistance to diabetes in BALB/c mice and
      did not affect diabetes progression in ST2 knock-out (ST2KO) mice. We argued that
      a lower dose of CY may selectively eliminate Tregs while sparing effector T cells
      in BALB/c mice. Indeed, only a very low dose of CY (50 mg/kg b.w.) enhanced
      diabetes severity in ST2KO mice. This treatment eliminated Tregs in pancreatic
      lymph nodes in ST2KO mice, while markedly increasing the influx of CD8+, CD4+TNF
      alpha+, and CD4+IFN-gamma+ effector T cells (Teffs) in pancreata. Also, the
      aggravation of diabetes was accompanied with increased serum levels of TNF-alpha,
      IFN-gamma, and IL-17. Taken together, our data suggest that the prevailing Th2
      immune response in BALB/c mice may be responsible for the resistance to MLD-STZ
      diabetes and that ST2 gene deletion reveals the role of highly cyclophosphamide
      sensitive CD4+Foxp3+ regulatory T cells in the pancreatic lymph nodes in diabetes
      modulation.

PMID- 23142276
TI  - High and low sensation seeking adolescents show distinct patterns of brain
      activity during reward processing.
AB  - Previous research has shown that personality characteristics, such as sensation
      seeking (SS), are strong predictors of risk-taking behavior during adolescence.
      However, the relationship between levels of SS and brain response has not been
      studied during this time period. Given the prevalence of risky behavior during
      adolescence, it is important to understand neurobiological differences in reward
      sensitivity between youth with high and low SS personalities. To this end, we
      used functional magnetic resonance imaging (fMRI) to examine differences in brain
      activity in an adolescent sample that included 27 high (HSS) and 27 low sensation
      seekers (LSS), defined by the Impulsive Sensation Seeking scale of the Zuckerman
      Kuhlman Personality Questionnaire (Zuckerman et al., 1993). In the scanner,
      participants played a modified Wheel of Fortune decision-making task (Cservenka
      and Nagel, 2012) that resulted in trials with monetary Wins or No Wins. We
      compared age- and sex-matched adolescent HSS and LSS (mean age=13.94+/-1.05) on
      brain activity by contrasting Win vs. No Win trials. Our findings indicate that
      HSS show greater bilateral insular and prefrontal cortex (PFC) brain response on
      Win vs. No Win compared to LSS. Analysis of simple effects showed that while LSS
      showed comparable brain activity in these areas during Wins and No Wins, HSS
      showed significant differences in brain response to winning (activation) vs. not
      winning (deactivation), with between-group comparison suggesting significant
      differences in brain response, largely to reward absence. Group differences in
      insular activation between reward receipt and absence may suggest weak autonomic
      arousal to negative outcomes in HSS compared with LSS. Additionally, since the
      PFC is important for goal-directed behavior and attention, the current results
      may reflect that HSS allocate fewer attentional resources to negative outcomes
      than LSS. This insensitivity to reward absence in HSS may lead to a greater
      likelihood of maladaptive choices when negative consequences are not considered,
      and may be an early neural marker of decreased loss sensitivity that has been
      seen in addiction. This neurobiological information may ultimately be helpful in
      establishing prevention strategies aimed at reducing youth risk-taking and
      suggests value in further examination of neural associations with personality
      characteristics during adolescence. 

PMID- 23142277
TI  - Dopamine modulates processing speed in the human mesolimbic system.
AB  - Neural activity in mesolimbic brain regions scales with stimulus novelty but the
      mechanistic role of neurotransmitters in this process remains unclear. Here, we
      used magnetoencephalography together with psychopharmacological stimulation in
      healthy humans to demonstrate that the neuronal dynamics of novelty processing
      are temporally adaptive and flexible. In particular, enhanced dopaminergic (150mg
      levodopa) - but not cholinergic (8mg galantamine) - neurotransmission accelerated
      the onset of novelty signals within the medial temporal lobe (MTL) from ~300 to
      <100ms. Cholinergic stimulation, on the other hand, led to a shift in underlying
      neural substrates from medial temporal to prefrontal brain regions. Our findings
      indicate a causal role of dopamine in regulating the processing speed of novelty
      sensitive MTL neurons. Moreover, they suggest that the influence of MTL and
      prefrontal brain regions in novelty processing is mediated by the balance of
      dopamine and acetylcholine levels. 

PMID- 23142278
TI  - Successful memory encoding is associated with increased cross-frequency coupling
      between frontal theta and posterior gamma oscillations in human scalp-recorded
      EEG.
AB  - Although previous studies have established that successful memory encoding is
      associated with increased synchronization of theta-band and gamma-band
      oscillations, it is unclear if there is a functional relationship between
      oscillations in these frequency bands. Using scalp-recorded EEG in healthy human
      participants, we demonstrate that cross-frequency coupling between frontal theta
      phase and posterior gamma power is enhanced during the encoding of visual stimuli
      which participants later on remember versus items which participants subsequently
      forget ("subsequent memory effect," SME). Conventional wavelet analyses and
      source localizations revealed SMEs in spectral power of theta-, alpha-, and gamma
      band. Successful compared to unsuccessful encoding was reflected in increased
      theta-band activity in right frontal cortex as well as increased gamma-band
      activity in parietal-occipital regions. Moreover, decreased alpha-band activity
      in prefrontal and occipital cortex was also related to successful encoding.
      Overall, these findings support the idea that during the formation of new
      memories frontal cortex regions interact with cortical representations in
      posterior areas. 

PMID- 23142279
TI  - Neural activity related to self-initiating elaborative semantic encoding in
      associative memory.
AB  - During episodic memory encoding, elaborative encoding strategies have been
      related to greater performance on later memory tests. However, many clinical
      populations display a deficit in self-initiating encoding strategies. We designed
      an fMRI study to examine the neural correlates of self-initiating elaborative
      encoding. Twenty-three healthy participants were presented triads of objects in
      which either neither, one or both objects in the bottom of the triad were related
      to the top object, and given two encoding instructions that required them to
      indicate the number of semantic ("related?") or physical ("smaller?")
      relationships in the triad. Reaction time decreased with more semantic
      relationships for both encoding instructions, indicating that semantic analysis
      was performed during the non-semantic encoding task. Recognition memory was
      better for the semantic encoding condition ("related?"), but there was no
      modulation of the number of semantic links on memory performance for either
      encoding condition. We performed a conjunction analysis on the fMRI data to find
      areas with greater activity for the non-semantic>semantic encoding tasks that
      were modulated by increasing semantic relationships during non-semantic encoding.
      Activity was found in the left dorsolateral prefrontal cortex (DLPFC) and
      bilaterally in the supramarginal gyrus. We suggest that the DLPFC is the most
      likely candidate region for the self-initiation of elaborative encoding while the
      supramarginal activity is likely related to attentional effects.

PMID- 23142280
TI  - Increasing stability and transport efficiency of supported liquid membranes
      through a novel ultrasound-assisted preparation method. Its application to
      cobalt(II) removal.
AB  - A novel ultrasound assisted method for preparing supported liquid membranes is
      described in this paper. The stability and efficiency of the supported liquid
      membrane obtained was tested by removing cobalt(II) from aqueous solutions
      through a facilitated countertransport mechanism using CYANEX 272 as carrier and
      protons as counterions. The results are compared with those obtained using
      supported liquid membranes prepared by soaking the polymeric material in the
      organic solution of the carrier at atmospheric pressure and under vacuum, both
      for 24h. Higher transport efficiency (>5%), flux (~18%), permeability (~20%) and
      stability (>6% in the second run and ~10% in the third run) were obtained by the
      supported liquid membrane prepared using the ultrasound assisted method. These
      findings can be explained by the effects of cavitation and acoustical streaming -
      which result from the ultrasound passing through the organic solution of the
      extractant - on the porous structure of the polymer support and on the pore
      filling.

PMID- 23142281
TI  - IPD-196, a novel phosphatidylinositol 3-kinase inhibitor with potent anticancer
      activity against hepatocellular carcinoma.
AB  - As the activation of phosphatidylinositol 3-kinase (PI3K) is associated with a
      wide variety of human malignancies, it is emerging as an attractive target for
      cancer treatment. In this study we synthesized a novel PI3Kalpha inhibitor, IPD
      196 [ethyl 6-(5-(2,4-difluorophenylsulfonamido)pyridin-3-yl)imidazo[1,2
      a]pyridine-3-carboxylate], and evaluated its anticancer effects on human
      hepatocellular carcinoma (HCC) cells. IPD-196 effectively inhibited the
      phosphorylation of downstream PI3K effectors such as Akt, mTOR, p70S6K, and 4E
      BP1, and its antiproliferative effect was more potent than that of sorafenib or
      LY294002. It also induced cell cycle arrest at the G0/G1 phase as well as
      apoptosis by increasing the proportion of sub-G1 apoptotic cells, and the levels
      of cleaved PARP, caspase-3, and caspase-9. Furthermore, it decreased the
      expression of HIF-1alpha and VEGF in Huh-7 cells, and inhibited tube formation
      and migration of human umbilical vein endothelial cells, which was confirmed by a
      Matrigel plug assay in mice. Taken together, IPD-196 exhibited its anticancer
      activity through disruption of the PI3K/Akt pathway that caused cell cycle
      arrest, apoptosis induction, and inhibition of angiogenesis in human HCC cells.
      We therefore suggest that IPD-196 may be a potential candidate drug for targeted
      HCC therapy.

PMID- 23142282
TI  - MiR-29c suppresses invasion and metastasis by targeting TIAM1 in nasopharyngeal
      carcinoma.
AB  - Based on microarray analysis, we previously reported that miR-29c is
      significantly downregulated in nasopharyngeal carcinoma (NPC). However, little is
      known about the effect and molecular mechanisms of action of miR-29c deregulation
      during the development and progression of NPC. Quantitative RT-PCR demonstrated
      that miR-29c was significantly downregulated in NPC cell lines and clinical
      specimens. Wound healing, Transwell migration and lung metastasis assays
      demonstrated that ectopic expression of miR-29c inhibited NPC cell migration and
      invasion in vitro and suppressed the formation of lung metastases in vivo. T cell
      lymphoma invasion and metastasis 1 (TIAM1) was confirmed as a miR-29c target gene
      using luciferase reporter assays, quantitative RT-PCR and Western blotting.
      Ectopic expression of TIAM1 significantly promoted the migration and invasion of
      SUNE-1 cell line stably overexpressing miR-29c. The prognostic value of TIAM1 was
      analyzed in 217 NPC patients using immunohistochemistry. Strikingly, patients
      with high TIAM1 expression had poorer overall, disease-free and distant
      metastasis-free survival than patients with low TIAM1 expression. Furthermore,
      multivariate Cox regression analysis revealed that TIAM1 could serve as an
      independent prognostic factor in NPC. The newly identified miR-29c/TIAM1 pathway
      further elucidates the molecular mechanisms regulating invasion and metastasis in
      NPC, and may provide novel prognostic and treatment strategies for NPC patients.

PMID- 23142283
TI  - MicroRNA-29c enhances the sensitivities of human nasopharyngeal carcinoma to
      cisplatin-based chemotherapy and radiotherapy.
AB  - This study was aimed to investigate the potential role of microRNA-29c (miR-29c)
      in regulating the sensitivities of nasopharyngeal carcinoma (NPC) to ionizing
      radiation (IR) and cisplatin. Low expression of miR-29c was positively associated
      with therapeutic resistance in 159 NPC cases. Our further in vitro and in vivo
      studies illustrated ectopic restoration of miR-29c substantially enhanced the
      sensitivity of NPC cells to IR and cisplatin treatment by promoting apoptosis.
      Furthermore, we detected miR-29c repressed expression of anti-apoptotic factors,
      Mcl-1 and Bcl-2 in NPC tissues and cell lines. These data indicate miR-29c might
      serve as a potential therapeutic sensitizer in NPC treatment.

PMID- 23142284
TI  - Hypoxia-inducible factor 1 alpha mediates epidermal growth factor-induced down
      regulation of E-cadherin expression and cell invasion in human ovarian cancer
      cells.
AB  - Hypoxia-inducible factor 1alpha (HIF-1alpha) regulates the transcription of a
      number of genes under hypoxia and other extracellular stimulations. It has been
      shown that E-cadherin is down-regulated by epidermal growth factor receptor (EGF)
      stimulation, and that cells with low E-cadherin expression are more invasive. Our
      recent study demonstrated a novel mechanism by which EGF down-regulates E
      cadherin expression through production of hydrogen peroxide (H(2)O(2)) and the
      activation of p38 MAPK in human ovarian cancer cells. In this study, we were
      interested in examining the potential role of HIF-1alpha in cell invasion under
      normoxic conditions, specifically when cells are treated with EGF, which is known
      to down-regulate E-cadherin and increase invasiveness. We show that EGF treatment
      induces HIF-1alpha expression in two human ovarian cancer cell lines (SKOV3 and
      OVCAR5), and that this effect is diminished by treatment with a membrane
      permeable H(2)O(2) scavenger, PEG-catalase. However, the induction of HIF-1alpha
      by EGF did not require the activation of p38 MAPK. Treatment with siRNA targeting
      HIF-1alpha reduces both basal and EGF-induced HIF-1alpha levels. Importantly,
      treatment with HIF-1alpha siRNA diminishes the up-regulation of Snail and Slug as
      well as the down-regulation of E-cadherin by EGF. The involvement of HIF-1alpha
      in the down-regulation of E-cadherin was confirmed with cobalt chloride
      (CoCl(2)), a hypoxia-mimetic reagent. Finally, we also show that EGF-induced cell
      invasion is attenuated by treatment with HIF-1alpha siRNA. This study
      demonstrates an important role for HIF-1alpha in mediating the effects of EGF on
      Snail, Slug and E-cadherin expression as well as invasiveness in human ovarian
      cancer cells.

PMID- 23142285
TI  - Celecoxib antagonizes the cytotoxic effect of cisplatin in human gastric cancer
      cells by decreasing intracellular cisplatin accumulation.
AB  - Cisplatin is a chemotherapeutic drug widely used for the treatment of gastric
      cancer. The benefit of including COX-2-selective inhibitors in cisplatin-based
      regimens on anti-cancer effect remains uncertain. In the present study, celecoxib
      and SC-236 antagonized cisplatin-induced cytotoxicity and apoptosis, whereas
      indomethancin and nimesulide exerted no effect, implying a COX-2-independent
      mechanism. Celecoxib decreased whole-cell cisplatin accumulation and DNA
      platination, resulting from reduced influx. In addition, combined treatment did
      not elicit greater antitumor activity than cisplatin or celecoxib monotherapy in
      vivo in a gastric xenograft model. Therefore, treatment strategies with celecoxib
      in combination with cisplatin should act cautiously.

PMID- 23142286
TI  - Vitamin D and breast cancer: emerging concepts.
AB  - The benefit of vitamin D in cancer prevention and to certain extent therapy has
      been well recognized. The active form of vitamin D, 1,25-dihydroxycholecalciferol
      (1,25(OH)2 D3) is a natural ligand for vitamin D receptor (VDR). Since
      1,25(OH)2D3 exerts toxic effects at a concentration that is beneficial, nearly
      1500 analogs of vitamin D have been synthesized and evaluated for their efficacy
      in a variety of carcinogenesis and human cancer models both in vitro and in vivo.
      Among these only a handful of them have been approved for evaluation in clinical
      trials for leukemia, breast, prostate and colon cancers. The mechanism of vitamin
      D action is mediated by the nuclear VDR and the signaling cascade for its action
      is extensively reported. In this review we focus on the newer concepts for
      vitamin D action. These include (1) differential effects of vitamin D in
      maintaining cell proliferation when the cells are under stress but suppressing
      cell growth when the cells are transformed; (2) functional significance of VDR
      polymorphism in potential vitamin D responsiveness; (3) regulation of
      constitutive splicing of vitamin D target gene, CYP24a, by the hormone and its
      significance; and (4) regulation of microRNA by vitamin D in breast cancer. It is
      anticipated that the new work in these selective areas would expand the
      understanding of vitamin D in breast cancer prevention and therapy. 

PMID- 23142287
TI  - Comprehensive genome sequencing of the liver cancer genome.
AB  - Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death
      worldwide. Recently, comprehensive whole genome and exome sequencing analyses for
      HCC revealed new cancer-associated genes and a variety of genomic alterations. In
      particular, frequent genetic alterations of the chromatin remodeling genes were
      observed, suggesting a new potential therapeutic target for HCC. Sequencing
      analysis has further identified the molecular complexities of multicentric
      lesions and intratumoral heterogeneity. Detailed analyses of the somatic
      substitution pattern of the cancer genome and the HBV virus genome integration
      sites by using whole-genome sequencing will elucidate the molecular basis and
      diverse etiological factors involved in liver cancer development. 

PMID- 23142288
TI  - Gankyrin plays an essential role in estrogen-driven and GPR30-mediated
      endometrial carcinoma cell proliferation via the PTEN/PI3K/AKT signaling pathway.
AB  - Gankyrin has been implicated in the formation of multiple cancer types, although
      its roles in estrogen-driven endometrial carcinoma remain unclarified. We
      evaluated the expression of Gankyrin in endometrial tissues and further explored
      its roles in estrogen-driven and GPR30-mediated endometrial cancer cell
      proliferation. Gankyrin was overexpressed in endometrial carcinoma tissues and
      showed an inverse relationship with the pattern of PTEN expression. The depletion
      or overexpression of Gankyrin induced endometrial cancer cell proliferation
      inhibition or expansion, respectively, which was associated with estrogen-driven
      GPR30 signaling via the PTEN/PI3K/AKT pathway. This study suggests that Gankyrin
      is functional in endometrial cancer development.

PMID- 23142289
TI  - Sorafenib potentiates irradiation effect in hepatocellular carcinoma in vitro and
      in vivo.
AB  - The multikinase-inhibition action of sorafenib provides strong rationales for its
      combination use with radiotherapy. We investigated the in vitro and in vivo
      effect of sorafenib combined with irradiation on hepatocellular carcinoma (HCC).
      Sorafenib enhanced radiosensitivity of human HCC cell lines in a schedule
      dependent manner. Sorafenib selectively inhibited radiation-induced activation of
      vascular endothelial growth factor receptor-2 (VEGFR2) and downstream
      extracellular signal-regulated kinase (ERK) pathway, induced DNA damage and
      suppressed DNA repair capacity, decreased radiation-activated NF-kappaB and
      increased radiation-induced apoptosis. In xenograft experiments, combination
      treatment produced marked tumor growth delay in both concurrent and sequential
      schedules. These results suggest that sorafenib could potentiate irradiation
      effect in HCC, which warrants further investigation for its potential clinical
      applications.

PMID- 23142290
TI  - Cancer heterogeneity and "the struggle for existence": diagnostic and analytical
      challenges.
AB  - The notions of inter- and intra-tumour heterogeneity (ITH) have been recognised
      for many years but recent advances in sequencing technology are allowing the true
      extent of both forms of heterogeneity to be revealed in detail for the first
      time. In this review we examine the current evidence for ITH, the possibility of
      cancers following a branched rather than linear evolutionary path and the
      potential implications both of these may have for the mechanisms of drug
      resistance acquisition. We also note that although clearly present in many cases,
      heterogeneity and branched evolution are not universal, with cases of tumour
      homogeneity and linear evolution still detected relatively frequently. The
      complexity induced by cases of ITH presents a considerable challenge for
      bioinformatics analyses and we illustrate this by describing the specific case of
      point mutation detection and a number of approaches which have been taken to
      combat these issues. Equally, the sequencing procedures which generate these data
      are rendered much more difficult in the face of ITH and we present a discussion
      of these problems in addition to describing some of the alternate paradigms being
      considered to overcome them. 

PMID- 23142291
TI  - Therapy of Smac mimetic SM-164 in combination with gemcitabine for pancreatic
      cancer.
AB  - Pancreatic cancer (PC) is a lethal solid malignancy with resistance to
      traditional chemotherapy. We investigated therapy of PC with SM-164 and
      gemcitabine alone and in combination. Survival of PC cells was reduced as the
      dose of SM-164 increased. SM-164 and/or gemcitabine increased the number of
      apoptotic and dead PC cells, and expression of cleavage fragments of caspase-3
      and PARP1, and inhibited tumor xenograft growth in nude mice. The inhibitory
      effect of combination treatment was greater and of longer duration than
      monotherapy. Neither combination nor monotherapy showed any significant toxicity
      in vivo. Apoptosis and necrosis, decreased expression of Ki67, and increased
      expression of cleaved caspase-3 were observed in xenograft tumor tissues in
      SM164/gemcitabine-treated mice. SM-164 could be a promising new agent for
      treatment of PC in combination with gemcitabine.

PMID- 23142292
TI  - Up-regulation of microRNA-1290 impairs cytokinesis and affects the reprogramming
      of colon cancer cells.
AB  - Abnormal cytokinesis increases the possibility of nuclear fusion in tumor cells.
      However, the role of microRNAs (miRNAs) in abnormal cytokinesis is unclear. Here,
      we found that miR-1290 was significantly up-regulated in clinical colon cancer
      tissues. Up-regulation of miR-1290 postponed cytokinesis and led to the formation
      of multinucleated cells. KIF13B was a target of miR-1290 that was involved in
      aberrant cytokinesis. Furthermore, enforced expression of miR-1290 activated the
      Wnt pathway and increased the reprogramming-related transcript factors c-Myc and
      Nanog. Our results suggest that up-regulation of miR-1290 in colon cancer cells
      impaired cytokinesis and affected reprogramming.

PMID- 23142293
TI  - Cidofovir treatment improves the pathology caused by the growth of human
      papillomavirus-positive cervical carcinoma xenografts in athymic nude mice.
AB  - Cidofovir has shown antiproliferative effects against human papillomavirus (HPV)
      positive cells and successfully suppressed the growth of HPV-positive xenografts
      in athymic nude mice. The present study evaluated the effect of cidofovir on
      several disease parameters in this animal model. Intratumoral administration of
      cidofovir resulted in a beneficial effect on body weight gain, a reduction in
      splenomegaly, a partial restoration of tryptophan catabolism, and diminished the
      inflammatory state induced by the xenografts. Administration of cidofovir to
      tumor-free animals did not have a direct effect on these parameters. Beyond
      suppressing tumor growth, intratumoral treatment with cidofovir ameliorated the
      pathology associated with HPV-tumor growth.

PMID- 23142294
TI  - Built to break: the antenna of a primitive insect, Petrobius brevistylis
      (Archaeognatha).
AB  - Jumping bristletails (Archaeognatha) have flagellate antennae with frequent
      breakpoints, structures destined to break when undue mechanical stress is
      applied. In natural populations of Petrobius brevistylis at least 67% of animals
      had broken antennae. In twenty-four trials, all antennae broke at a breakpoint
      under the animal's weight. Breakpoints consist of two cylinders of laminated
      cuticle, one stuck inside the other. For half the length of the breakpoint the
      cylinders are separated by a non-laminated layer of cuticle; thus a tripartite
      cuticle is formed. During a breakage, the two cylinders slide apart along that
      non-laminated middle layer that seems to act like a lubricant. While the
      cylinders pull apart, a thin cuticle unfolds that closes off the new tip of the
      antenna formed by the outer breakpoint cylinder. Later on, the cylinder is not
      replaced by a new terminal antennomere. Instead, the antennomere directly
      proximal to a breakpoint, i.e. the one that after the break forms the last
      antennomere, already possess the same complement of sensilla as the original
      terminal antennomere. This includes sensilla basiconica Type A and B found
      exclusively on these antennomeres and the original terminal antennomere.
      Breakpoints are common to Archaeognatha and Thysanura, insects that moult
      throughout their lifetime.

PMID- 23142295
TI  - Comparison of osteochondral autologous transplantation, microfracture, or
      debridement techniques in articular cartilage lesions associated with anterior
      cruciate ligament injury: a prospective study with a 3-year follow-up.
AB  - PURPOSE: To compare the concomitant treatment of articular cartilage damage in
      the medial femoral condyle with osteochondral autologous transplantation (OAT),
      microfracture, or debridement procedures at the time of anterior cruciate
      ligament (ACL) reconstruction. METHODS: Between 2006 and 2009, 102 patients with
      a mean age of 34.1 years and with an ACL rupture and articular cartilage damage
      in the medial femoral condyle of the knee were randomized to undergo OAT,
      microfractures, or debridement at the time of ACL reconstruction. A matched
      control group was included, comprising 34 patients with intact articular
      cartilage at the time of ACL reconstruction. There were 34 patients in the OAT
      ACL group, 34 in the microfracture (MF)-ACL group, 34 in the debridement (D)-ACL
      group, and 34 in the control group with intact articular cartilage (IAC-ACL
      group). The mean time from ACL injury to operation was 19.32 +/- 3.43 months, and
      the mean follow-up was 36.1 months (range, 34 to 37 months). Patients were
      evaluated with the International Knee Documentation Committee (IKDC) score,
      Tegner activity score, and clinical assessment. RESULTS: Of 102 patients, 97
      (95%) were available for the final follow-up. According to the subjective IKDC
      score, all 4 groups fared significantly better at the 3-year follow-up than
      preoperatively (P < .005). The OAT-ACL group's IKDC subjective knee evaluation
      was significantly better than that of the MF-ACL group (P = .024) and D-ACL group
      (P = .018). However, the IKDC subjective score of the IAC-ACL group was
      significantly better than the OAT-ACL group's IKDC evaluation (P = .043). There
      was no significant difference between the MF-ACL and D-ACL groups' IKDC
      subjective scores (P = .058). Evaluation of manual pivot-shift knee laxity
      according to the IKDC knee examination form showed similar findings for the 4
      groups immediately postoperatively and at 3-year follow-up, and the findings were
      rated as normal or nearly normal (IKDC grade A or B) in 29 of 33 patients (88%)
      in the OAT-ACL group, 28 of 32 patients (88%) in the MF-ACL group, 27 of 32
      patients (84%) in the D-ACL group, and 31 of 34 patients (91%) in the IAC-ACL
      group. CONCLUSIONS: Our study shows that intact articular cartilage during ACL
      reconstruction yields more favorable IKDC subjective scores compared with any
      other articular cartilage surgery type. However, if an articular defect is
      present, the subjective IKDC scores are significantly better for OAT versus
      microfracture or debridement after a mean period of 3 years. Anterior knee
      stability results were not significantly affected by the different articular
      cartilage treatment methods. LEVEL OF EVIDENCE: Level II, prospective comparative
      study.

PMID- 23142296
TI  - Arthroscopic synovectomy of the ankle in rheumatoid arthritis.
AB  - PURPOSE: To evaluate the outcome of arthroscopic synovectomy of the ankle joint
      in patients with early-stage rheumatoid arthritis (RA). METHODS: Between 2005 and
      2009, 18 consecutive patients with RA involving the ankle underwent arthroscopic
      synovectomy. Pain was measured using a visual analog scale (VAS), and clinical
      outcome was determined by calculating the American Orthopaedic Foot and Ankle
      Society (AOFAS) Ankle-Hindfoot Scale score with a mean follow-up of 5 years (60
      months). Assessments were performed preoperatively, at 6 and 12 months
      postoperatively, and then yearly thereafter. Clinical success was defined as the
      absence of synovitis symptoms or when patients demonstrated good or excellent
      outcomes (AOFAS Ankle-Hindfoot Scale score >=80) with >50% improvement in VAS
      score for pain. Demographic, laboratory, and radiological variables were
      evaluated to determine possible factors predicting clinical outcome. RESULTS: VAS
      and AOFAS scores were significantly improved at the final follow-up (60 months; P
      < .0001). The greatest improvements in clinical scores were observed after 12
      months; thereafter, they steadily declined. Of the 18 patients examined, 14
      (77.8%) were considered to have had clinical success with no reintervention.
      Variables predictive of clinical success were short duration of symptoms (P =
      .042) and minimal radiographic changes based on the Larsen grading system (P =
      .030). CONCLUSIONS: Arthroscopic synovectomy is a safe and successful procedure
      in ankle joints affected by RA. The best clinical outcomes are achieved when the
      procedure is performed early in the disease course and when there is no evidence
      of cartilage degeneration. LEVEL OF EVIDENCE: Level IV, prognostic case series.

PMID- 23142297
TI  - Diagnosis of subscapularis tendon tears: are available diagnostic tests pertinent
      for a positive diagnosis?
AB  - HYPOTHESIS: Clinically, subscapularis tendon tears are suggested by the presence
      of increased passive external rotation compared to the opposite side, resisted
      internal rotation manoeuvres (Lift-Off test [LOT], Belly-Press test [BPT],
      Napoleon test and Bear-Hug test [BHT] and positive Internal Rotation Lag Sign
      and/or Belly-Off Signs). Associated bicipital involvement is frequent with
      subscapularis tendon tears, because it participates in the formation of the
      biceps pulley. The Palm-Up test (PUT) is used for the biceps, and the Jobe test
      for the supraspinatus. MATERIAL AND METHODS: In this multicenter study, we
      evaluated the positive diagnostic value of the clinical tests, LOT, BPT, BHT,
      PUT, and the Jobe test for subscapularis tears as well as their anatomical value.
      The relationships of the different parameters studied were compared statistically
      by analysis of variance (ANOVA). This prospective multicenter study was performed
      from January 2009 to February 2010 and included 208 cases of subscapularis tendon
      tears, isolated or associated with partial (Ellman 1, 2 or 3) or full thickness
      (SFA stage 1) supraspinatus tears. RESULTS: The severity of the subscapularis
      tear was quantified according to the SFA classification into four stages and
      according to the level of injury (the lower 1/3 and upper 2/3). The three tests
      LOT, BPT and BHT were correlated to the severity of observed tears (P<0.05). The
      more deficient the test results were, the more severe the anatomical damage. The
      LOT is the test that cannot be performed most often (18%) but when it is
      positive, it is predictive of very severe tears. The BHT is the most sensitive of
      all tests (82%). The frequency of biceps involvement was correlated to the
      severity of subscapularis damage. There was no significant correlation between
      biceps involvement and subscapularis tests, or between supraspinatus involvement
      and subscapularis tests. There was no correlation between the Palm-Up test and
      subscapularis tears with associated supraspinatus involvement however, it was
      significantly correlated to biceps involvement (P<0.05). The Jobe test was
      disappointing because it was often positive even for isolated subscapularis
      tears. CONCLUSION: Even though all three tests were performed (LOT, BPT, BHT),
      24% of the subscapularis tears were only diagnosed during surgery. The role of
      the Internal Rotation Lag Sign and Belly-Off Sign in improving the diagnosis of
      tears was not studied in this work.

PMID- 23142299
TI  - Scarf osteotomy without internal fixation to correct hallux valgus.
AB  - Scarf osteotomy of the first metatarsal bone to correct hallux valgus deformity
      has benefited from a number of improvements over the past two decades, most
      notably regarding the internal fixation method. Internal fixation was deemed
      mandatory by the authors of early case-series studies. Maestro suggested
      eliminating the proximal screw by locking the two fragments distally: a notch was
      created via a medial extension of the cephalic part of the osteotomy, the plantar
      fragment was displaced laterally, and the distal end of the proximal fragment was
      then fit into the notch (secondary cut and interlocking joint technique). To
      further develop this concept and to increase the potential range of translation,
      we developed an original technique involving distal locking without shortening
      and proximal stabilisation by impaction of a cortical-cancellous bone graft taken
      from the medial overhanging edge of the proximal fragment. This original
      technical variant has not been reported previously.

PMID- 23142300
TI  - Seasonal influenza vaccine efficacy and its determinants in children and non
      elderly adults: a systematic review with meta-analyses of controlled trials.
AB  - CONTEXT: The true level of influenza vaccine efficacy is controversial and many
      factors may influence its estimation. OBJECTIVES: To estimate the efficacy of
      vaccination of children and non-elderly adults for the prevention of influenza
      and to explore the impact of type of vaccine, age, degree of strain matching,
      influenza type and case ascertainment methods on vaccine efficacy estimates. DATA
      SOURCES: Medline and EmBase databases until October 2011. References of relevant
      articles were also reviewed. STUDY SELECTION: Controlled trials evaluating
      seasonal influenza vaccines and presenting incidence of laboratory-confirmed
      influenza illness were eligible. Studies exploring efficacy after experimental
      challenge, presenting duplicate data, employing group randomization, or focusing
      on special populations were excluded. DATA EXTRACTION: The vaccine effect on
      influenza prevention was evaluated by calculating Mantel-Haenszel risk ratios
      (RR) and using random-effects models. Vaccine efficacies were calculated for each
      comparison as (1-RR)*100. RESULTS: Thirty studies were included in one or more of
      a total of 101 analyses, comprising 88.468 study participants. There was evidence
      of heterogeneity in 49% of the analyses. Summary vaccine efficacy was 65% against
      any strain, 78% against matched strains and 55% against not-matched strains. Both
      live-attenuated and inactivated vaccines showed similar levels of protection
      against not-matched strains (60% and 55%, respectively). Live-attenuated vaccines
      performed better than inactivated vaccines in children (80% versus 48%), whereas
      inactivated vaccines performed better than live-attenuated vaccines in adults
      (59% versus 39%). There was a large difference (20%) in efficacy against
      influenza A (69%) and influenza B (49%) types for not-matched strains. Summary
      estimates of vaccine efficacy were highest when ascertainment was based on
      culture confirmation. CONCLUSION: Influenza vaccines are efficacious, but
      efficacy estimates depend on many variables including type of vaccine and age of
      vaccinees, degree of matching of the circulating strains to the vaccine,
      influenza type, and methods of case ascertainment.

PMID- 23142301
TI  - Hepatitis B vaccination: a completed schedule enough to control HBV lifelong?
      Milan, Italy, 17-18 November 2011.
AB  - The Viral Hepatitis Prevention Board (VHPB) organized an international meeting in
      Milan in November 2011 on the question of whether completing a course of
      hepatitis B vaccination confers lifelong protection against hepatitis B virus
      infection and its complications. Presentations covered vaccine efficacy including
      factors influencing long-term protection; breakthrough infections; the
      immunological effect of natural boosting; the effectiveness of universal
      hepatitis B vaccination in different countries, and issues relating to national,
      regional and global policies on booster vaccination. Findings from four
      continents were presented at the meeting, with data now extending to follow-up
      for nearly 30 years after full primary vaccination. The results reported add to
      the extensive and growing body of knowledge, demonstrating that in spite of
      subsequent decline and ultimate loss of detectable serum anti-HBs, a full primary
      course of hepatitis B vaccine confers complete protection against acute clinical
      disease and chronic hepatitis B infection for long periods of time. Our
      understanding of the role and functions of T and B cells in protective immunity
      deepens, although the picture is still complex. A framework for future work in
      several areas emerged from the meeting, including monitoring and surveillance of
      vaccination programmes, breakthrough infections, hepatitis B in immigrant
      populations, and vaccine-escape viral mutants. One further concrete
      recommendation is the setting up of a working group to standardize definitions on
      terms such as "immunity", "protection", "immune memory", "non-responders", "long
      term", "anamnestic response", "breakthrough" and "vaccine failure".

PMID- 23142302
TI  - Impact of anti-orthopoxvirus neutralizing antibodies induced by a heterologous
      prime-boost HIV-1 vaccine on insert-specific immune responses.
AB  - BACKGROUND: The impact of anti-vector immunity on the elicitation of insert
      specific immune responses is important to understand in vaccine development. HVTN
      055 was a 150 person phase I randomized, controlled HIV vaccine trial of
      recombinant modified vaccinia Ankara (rMVA) and fowlpox (rFPV) with matched HIV-1
      inserts which demonstrated increased CD8+ T-cell immune responses in the
      heterologous vaccine group. The controls used in this study were the empty
      vectors (MVA and FPV). METHODS: Anti-MVA and anti-vaccinia neutralizing
      antibodies (NAbs) were measured and compared with cellular and humoral HIV-1
      specific immune responses. RESULTS: Elicitation of anti-vector responses
      increased with increasing dose of MVA and up to 2 administrations. Further
      inoculations of MVA (up to 5) did not increase the magnitude of the anti-MVA
      response but did delay the anti-vector NAb titre decay. There was no evidence
      that the insert impaired the anti-vector response, nor that anti-vector immunity
      attenuated the insert-specific responses. CONCLUSION: Two doses of MVA may be
      ideal for the elicitation of orthopoxvirus immune responses with further doses
      maintaining increased titres against the vector. We found no evidence that
      eliciting HIV insert- or MVA vector-specific immune responses interfered with
      elicitation of immune responses to the other.

PMID- 23142303
TI  - Influenza vaccination rates and determinants among Spanish medical students.

PMID- 23142304
TI  - Antibody repertoire development in fetal and neonatal piglets. XV. Porcine
      circovirus type 2 infection differentially affects serum IgG levels and
      antibodies to ORF2 in piglets free from other environmental factors.
AB  - Porcine circovirus type 2 (PCV2) is an important pathogen in the porcine
      respiratory disease complex (PRDC) and its persistence may be due to
      dysregulation of systemic immunity. We examined this contention using isolator
      piglets. We present data on Ig levels in serum and bronchio-alveolar lavage
      (BAL), on antibody response to PCV2 and to TNP conjugates used as model antigens
      in 48 PCV2-infected isolator piglets. We compared these to data from TNP
      immunized isolator piglets colonized with a probiotic flora, those infected with
      swine influenza (S-FLU) and those infected with porcine respiratory and
      reproductive syndrome virus (PRRSV). We found that PCV2 infection does not cause
      generalized hypergammaglobulinemia that characterizes PRRSV infections, but
      causes an unexplained increase in serum IgA. All animals had serum IgG to the
      ORF2 gene product of PCR2, but neither IgA nor IgG anti-ORF2 responses in BAL.
      PCV2 infection is a poor adjuvant since only natural anti-TNP antibodies were
      found. Unexpectedly, immunization appeared to result in lower Ig levels and lower
      anti-ORF2 responses. There was extreme variation in serum Ig levels in response
      to infection that could in part be traced to genetic and gender differences.
      These data suggest that non-replicating vaccines are unlikely to result in a
      significant primary antibody response but may prime the system for a secondary
      antibody and cytotoxic response following actual infection. In any case,
      developers may have to contend with significant genetic differences in the
      response of piglets to PCV2.

PMID- 23142305
TI  - Factors affecting repeated influenza vaccination among older people in Taiwan.
AB  - OBJECTIVE: This study identifies factors that influence repeated influenza
      vaccination among people aged 65 years and older in Taiwan. METHODS: Data of this
      retrospective cohort study were drawn from the 2005 National Health Interview
      Survey and the 2005-2007 National Health Insurance claims data; a sample of 1384
      older people was analyzed. The pattern of repeated influenza vaccination was
      divided into 3 groups: unvaccinated all 3 years, vaccinated 1-2 times over 3
      years, and vaccinated all 3 years. Multinomial logistic regression analyses were
      performed. RESULTS: Only 20.6% of older people were vaccinated all 3 years. Those
      70-74 years of age (odds ratio [OR]=1.81), living in rural areas (OR=2.47),
      having one (OR=2.07) or more (OR=2.41) chronic conditions, frequent outpatient
      visits (OR=1.48), and undergoing preventive health examinations (OR=2.22) were
      more likely to have repeated vaccinations. However, those with difficulties
      performing one or more activities of daily living (ADL difficulty) (OR=0.41) and
      seeking care from alternative medicine (OR=0.48) were less likely to undergo
      regular vaccinations. CONCLUSION: The repeated influenza vaccination rates in our
      Taiwan sample were far from optimal. Factors identified in this analysis may help
      to improving influenza vaccination programs.

PMID- 23142306
TI  - Differences of IgG antibody avidity after an acellular pertussis (aP) booster in
      adolescents after a whole cell (wcP) or aP primary vaccination.
AB  - Compared to whole cell pertussis (wcP) vaccines, acellular pertussis vaccines
      (aP) have a better safety profile with lower reactogenicity, although their short
      and long-term efficacy was found to be slightly lower. Up to now, no established
      serological parameter to predict long-term protection exists. IgG-anti-pertussis
      avidity possibly determines the effect of different pertussis vaccines and
      boosting intervals on long-term immunity. Thus, the avidity of a tetanus
      diphtheria-aP booster at 10-14 years was tested in three groups of adolescents
      who had been previously immunized with either five doses of aP (5aP) at 2, 4, 6,
      15-18 months and 5-6 years of age, four doses of aP (4aP) or four doses of wcP
      (4wcP) at 2, 4, 6 and 15-18 months of age. Relative avidity index (RAI) of IgG
      anti-pertussis toxin (PT) and IgG-anti-filamentous-hemagglutinin (FHA) was
      assessed by an adapted ELISA. RAI of IgG-anti-PT and of IgG-anti-FHA correlated
      positively with antibody concentrations in the pre-vaccination and in the post
      vaccination analysis and significantly increased after adolescent booster with aP
      in all groups. Pre- and post-vaccination, the proportion of participants with IgG
      anti-PT RAI>40% (moderate to high avidity) was significantly lower in the 4wcP
      group (52.9% and 88.9%) compared to the 5aP group (89.5% and 100.0%). In
      conclusion, TdaP in adolescence induces an increase of antibody avidity and,
      thus, is able to enhance the binding-quality of antibodies against pertussis. The
      study suggests including antibody avidity into serological studies on the humoral
      response to provide information about the long-term efficacy of the vaccine.

PMID- 23142307
TI  - Cost-effectiveness and economic benefits of vaccines in low- and middle-income
      countries: a systematic review.
AB  - BACKGROUND: Public health interventions that prevent mortality and morbidity have
      greatly increased over the past decade. Immunization is one of these preventive
      interventions, with a potential to bring economic benefits beyond just health
      benefits. While vaccines are considered to be a cost-effective public health
      intervention, implementation has become increasingly challenging. As vaccine
      costs rise and competing priorities increase, economic evidence is likely to play
      an increasingly important role in vaccination decisions. METHODS: To assist
      policy decisions today and potential investments in the future, we provide a
      systematic review of the literature on the cost-effectiveness and economic
      benefits of vaccines in low- and middle-income countries from 2000 to 2010. The
      review identified 108 relevant articles from 51 countries spanning 23 vaccines
      from three major electronic databases (Pubmed, Embase and Econlit). RESULTS:
      Among the 44 articles that reported costs per disability-adjusted life year
      (DALY) averted, vaccines cost less than or equal to $100 per DALY averted in 23
      articles (52%). Vaccines cost less than $500 per DALY averted in 34 articles
      (77%), and less than $1000 per DALY averted in 38 articles (86%) in one of the
      scenarios. 24 articles (22%) examined broad level economic benefits of vaccines
      such as greater future wage-earning capacity and cost savings from averting
      disease outbreaks. 60 articles (56%) gathered data from a primary source. There
      were little data on long-term and societal economic benefits such as morbidity
      related productivity gains, averting catastrophic health expenditures, growth in
      gross domestic product (GDP), and economic implications of demographic changes
      resulting from vaccination. CONCLUSIONS: This review documents the available
      evidence and shows that vaccination in low- and middle-income countries brings
      important economic benefits. The cost-effectiveness studies reviewed suggest to
      policy makers that vaccines are an efficient investment. This review further
      highlights key gaps in the available literature that would benefit from
      additional research, especially in the area of evaluating the broader economic
      benefits of vaccination in the developing world.

PMID- 23142308
TI  - U.S. Postlicensure safety surveillance for adolescent and adult tetanus,
      diphtheria and acellular pertussis vaccines: 2005-2007.
AB  - BACKGROUND: Pre-licensure clinical trials for two U.S. licensed tetanus toxoid,
      reduced diphtheria toxoid and acellular pertussis (Tdap) vaccines did not reveal
      any major safety concerns. However, routine use in large adolescent and adult
      populations could reveal rare and potentially serious adverse events (AEs).
      METHODS: To characterize reported AEs following Tdap vaccination and identify
      potential safety concerns warranting further evaluation, we analyzed data from
      the Vaccine Adverse Event Reporting System (VAERS) and assessed the frequency and
      proportions of AEs and reporting rates (reports per 100,000 vaccine doses
      distributed). RESULTS: A total of 2090 reports (7% were serious; 55% listed Tdap
      alone) involving Tdap vaccines were submitted to VAERS May 2005-June 2007. The
      crude reporting rate was 10.2 per 100,000 vaccine doses distributed. The median
      age of vaccinees was 22 years, and the female to male ratio was about 2 to 1. The
      majority of reports described common local and systemic signs and symptoms, such
      as injection site reactions, fever, and headache. Rarely reported AEs included
      myopericarditis, demyelinating diseases of the central nervous system, Guillain
      Barre Syndrome, syncope, encephalopathy/encephalitis, seizure, Bell's palsy,
      anaphylaxis, and thrombocytopenia. CONCLUSIONS: Because adolescents and adults
      were not routinely vaccinated against pertussis in the past, this surveillance
      summary provides important - and reassuring - information about the use of Tdap
      in these age groups. Although subject to the limitations of passive surveillance,
      the findings of this VAERS review support the pre-licensure clinical trial data
      with regard to the safety of the U.S. licensed Tdap vaccines. Continued
      monitoring of clinically significant AEs that are temporally associated with Tdap
      vaccination and further assessment of such events using controlled observational
      studies may provide additional information about the safety of these vaccines.

PMID- 23142309
TI  - Can the Pelargonium sidoides root extract EPs(r) 7630 prevent asthma attacks
      during viral infections of the upper respiratory tract in children?
AB  - INTRODUCTION: Asthma is a chronic disease characterized by airway inflammation.
      Viral infection initiates an immune inflammatory response that may produce asthma
      attacks. There is no effective preventing therapy for asthma attack during upper
      respiratory tract viral infections. OBJECTIVE: To investigate the efficacy of 5
      days of Pelargonium sidoides therapy for preventing asthma attack during upper
      respiratory tract viral infections. METHODS: Sixty one asthmatic children with
      upper respiratory tract viral infection were enrolled in the study. The patients
      were randomized to receive Pelargonium sidoides daily for 5 days (n=30) or not
      (n=31). Before and after treatment, they all were examined and symptom scores
      were determined. Following five days treatment, children were evaluated whether
      or not they had an asthma attack. RESULTS: Treatment with Pelargonium sidoides
      was not associated with a statistically significant differences in fever and
      muscle aches (p>0.05, Chi-square test). There were significant differences in
      cough frequency and nasal congestion between the groups (p<0.05, Chi-square
      test). There were statistically significant differences in having asthma attack
      between the groups (p<0.05, Chi-square). Pelargonium sidoides group had less
      frequency of asthma attack. DISCUSSION: Our study shows that Pelargonium sidoides
      may prevent asthma attacks during upper respiratory tract viral infections.

PMID- 23142310
TI  - Knowledge and practice of malaria prophylaxis among travel medicine consultants
      in Greece.
AB  - Malaria is among the most significant travel-related infections encountered by
      travellers to endemic countries in terms of morbidity and mortality. The aim of
      this study is to assess the knowledge and practices about malaria prophylaxis of
      travel medicine consultants in Greece. A standardized questionnaire was sent to
      travel medicine consultants in all 57 Regional Departments of Public Health which
      are the official travel medicine services in Greece. Seventy (66% response rate)
      travel medicine consultants participated in the survey. Of them, 34.3%, 17.1%,
      and 44.3% delivered >20, 6-20, and <=5 consultations per month, respectively. The
      average score of correct answers was 60% about malaria general knowledge and
      prophylaxis, and 60% about case scenarios. Linear regression revealed that being
      a physician and previous training in travel medicine were factors statistically
      significantly associated with higher rates of correct answers. Our results show
      inadequacies in knowledge and practices on malaria prophylaxis of travel medicine
      consultants in Greece. Continuing training and usage of credible information
      resources about malaria transmission and malaria prophylaxis in travellers will
      improve the quality of pre-travel advice provided by travel medicine consultants
      in Greece.

PMID- 23142311
TI  - Biology of brain metastases and novel targeted therapies: time to translate the
      research.
AB  - Brain metastases (BM) occur in 20% to 40% of patients with cancer and result in
      significant morbidity and poor survival. The main therapeutic options include
      surgery, whole brain radiotherapy, stereotactic radiosurgery and chemotherapy.
      Although significant progress has been made in diagnostic and therapeutic
      methods, the prognosis in these patients remains poor. Furthermore, the poor
      penetrability of chemotherapy agents through the blood brain barrier (BBB)
      continues to pose a challenge in the management of this disease. Preclinical
      evidence suggests that new targeted treatments can improve local tumor control
      but our clinical experience with these agents remains limited. In addition,
      several clinical studies with these novel agents have produced disappointing
      results. This review will examine the knowledge of targeted therapies in BM. The
      preclinical and clinical evidence of their use in BM induced by breast cancer,
      non-small cell lung cancer and melanoma will be presented. In addition, we will
      discuss the role of antiangiogenic and radiosensitising agents in the treatment
      of BM and the current strategies available to increase BBB permeability. A better
      understanding of the mechanism of action of these agents will help us to identify
      the best targets for testing in future clinical studies.

PMID- 23142312
TI  - A new balance index for phylogenetic trees.
AB  - Several indices that measure the degree of balance of a rooted phylogenetic tree
      have been proposed so far in the literature. In this work we define and study a
      new index of this kind, which we call the total cophenetic index: the sum, over
      all pairs of different leaves, of the depth of their lowest common ancestor. This
      index makes sense for arbitrary trees, can be computed in linear time and it has
      a larger range of values and a greater resolution power than other indices like
      Colless' or Sackin's. We compute its maximum and minimum values for arbitrary and
      binary trees, as well as exact formulas for its expected value for binary trees
      under the Yule and the uniform models of evolution. As a byproduct of this study,
      we obtain an exact formula for the expected value of the Sackin index under the
      uniform model, a result that seems to be new in the literature.

PMID- 23142313
TI  - Insights into the impact of phenolic residue incorporation at each position along
      secretin for receptor binding and biological activity.
AB  - Understanding of the structural importance of each position along a peptide
      ligand can provide important insights into the molecular basis for its receptor
      binding and biological activity. This has typically been evaluated using serial
      replacement of each natural residue with an alanine. In the current report, we
      have further complemented alanine scanning data with the serial replacement of
      each residue within secretin-27, the natural ligand for the prototypic class B G
      protein-coupled secretin receptor, using a photolabile phenolic residue. This not
      only provided the opportunity to probe spatial approximations between positions
      along a docked ligand with its receptor, but also provided structure-activity
      insights when compared with tolerance for alanine replacement of the same
      residues. The pattern of sensitivity to phenolic residue replacement was periodic
      within the carboxyl-terminal region of this peptide ligand, corresponding with
      alanine replacements in that region. This was supportive of the alpha-helical
      conformation of the peptide in that region and its docking within a groove in the
      receptor amino-terminal domain. In contrast, the pattern of sensitivity to
      phenolic residue replacement was almost continuous in the amino-terminal region
      of this peptide ligand, again similar to alanine replacements, however, there
      were key positions in which either the phenolic residue or alanine was
      differentially preferred. This provided insights into the receptor environment of
      the portion of this ligand most critical for its biological activity. As the
      structure of the intact receptor is elucidated, these data will provide a guide
      for ligand docking to the core domain and to help clarify the molecular basis of
      receptor activation.

PMID- 23142314
TI  - Ghrelin, leptin and insulin in cirrhotic children and adolescents: relationship
      with cirrhosis severity and nutritional status.
AB  - OBJECTIVE: Ghrelin, leptin, and insulin concentrations are involved in the
      control of food intake and they seem to be associated with anorexia-cachexia in
      cirrhotic patients. The present study aimed to investigate the relationship
      between the nutritional status and fasting ghrelin, leptin and insulin
      concentrations in pediatric cirrhotic patients. METHODS: Thirty-nine patients
      with cirrhosis and 39 healthy controls aged 0-15 years matched by sex and age
      were enrolled. Severity of liver disease was assessed by Child-Pugh
      classification, and Pediatric for End Stage Liver Disease (PELD) or Model for End
      stage Liver Disease (MELD) scores. Blood samples were collected from patients and
      controls to assay total ghrelin, acyl ghrelin, leptin and insulin by using a
      commercial ELISA kit. Anthropometry parameters used were standard deviation score
      of height-for-age and triceps skinfold thickness-for-age ratio. A multiple linear
      regression analysis was used to determine the correlation between dependent and
      independent variables. RESULTS: Acyl ghrelin was significantly lower in cirrhotic
      patients than in controls [142 (93-278) pg/mL vs 275 (208-481) pg/mL, P=0.001].
      After multiple linear regression analysis, total ghrelin and acyl ghrelin showed
      an inverse correlation with age; acyl ghrelin was associated with the severity of
      cirrhosis and des-acyl ghrelin with PELD or MELD scores >=15. Leptin was
      positively correlated with gender and anthropometric parameters. Insulin was not
      associated with any variable. CONCLUSION: Low acyl ghrelin and high des-acyl
      ghrelin concentrations were associated with cirrhosis severity, whereas low
      leptin concentration was associated with undernourishment in children and
      adolescents with cirrhosis.

PMID- 23142315
TI  - Critical residues in the transmembrane helical bundle domains of the human
      motilin receptor for erythromycin binding and activity.
AB  - The motilin receptor belongs to a family of Class I G protein-coupled receptors,
      and is an important endogenous regulator of gastrointestinal motor function.
      Motilin and erythromycin, two chemically distinct full agonists of the motilin
      receptor, are known to bind to distinct regions of this receptor, based on
      previous systematic mutagenesis of extracellular regions that dissociated the
      effects on these two agents. The action of these different chemical classes of
      agonists likely yields a common activation state of the cytosolic face of this
      receptor that is responsible for interaction with its G protein. In the current
      work, we studied the predicted transmembrane (TM) domains of this receptor for
      functional responses to motilin and erythromycin. Motilin receptor constructs
      were prepared in which each residue in the TM domains was mutated to alanine or
      valine. Each construct was expressed in COS cells and characterized for motilin
      and erythromycin binding and intracellular calcium responses stimulated by both
      agonists. Constructs with mutations of residues, Asp94, Leu95, Arg97 and Trp99 in
      TM2, Ser169 in TM4, and Tyr321 and Glu325 in TM6, were responsible for the
      negative impact on biological activity stimulated by erythromycin, but had no
      effect on motilin responses. On the other hand, constructs with mutations of
      residues, Leu113 in TM3, Pro172 in TM4, Trp250 and Tyr255 in TM5, and Gln334 in
      TM7, were negatively responsive to both erythromycin and motilin. These data
      support important roles of new regions in the TM domains of the motilin receptor
      for erythromycin action, suggesting differential mechanisms of actions by
      peptidyl and non-peptidyl ligands.

PMID- 23142316
TI  - Neuregulin-1beta regulates tyrosine kinase receptor expression in cultured dorsal
      root ganglion neurons with excitotoxicity induced by glutamate.
AB  - Neuregulin-1 (NRG-1) signaling regulates neuronal development, migration,
      myelination, and synaptic maintenance. Three members of tyrosine kinase receptor
      (Trk) family, TrkA, TrkB, and TrkC, have been identified in DRG neurons. Whether
      NRG-1beta and its signaling pathways influence the expression of these Trk
      receptors in DRG neurons is still unclear. In the present study, primary cultured
      DRG neurons were used to determine the effects of NRG-1beta on TrkA, TrkB, and
      TrkC expression in DRG neurons with excitotoxicity induced by glutamate (Glu).
      The involvement of phosphatidylinositol 3-kinase (PI3K)/Akt and the effects of
      extracellular signal-regulated protein kinase (ERK1/2) signaling pathways on NRG
      1beta were also determined. DRG neurons were cultured for 48h and then exposed to
      Glu, Glu plus NRG-1beta, LY294002 plus Glu plus NRG-1beta, PD98059 plus Glu plus
      NRG-1beta, and PD98059 plus LY294002 plus Glu plus NRG-1beta for an additional
      24h. The DRG neurons were continuously exposed to culture media as a control.
      After that, all cultures were processed for detection of mRNA levels of TrkA,
      TrkB, and TrkC using real time-PCR analysis. Protein levels of TrkA, TrkB, and
      TrkC were detected using a Western blot assay. The expression of TrkA, TrkB, and
      TrkC in situ was determined by a fluorescent labeling technique. The levels of
      phosphorylated Akt (pAkt), phosphorylated ERK1/2 (pERK1/2), total protein levels
      of Akt and ERK1/2 were detected using a Western blot assay. The results indicated
      that in primary cultured DRG neurons with excitotoxicity induced by Glu, NRG
      1beta increased the expression of TrkA and TrkB their mRNAs, but not TrkC and its
      mRNA. Inhibitors (LY294002, PD98059) either alone or in combination blocked the
      effects of NRG-1beta. NRG-1beta may play an important role in regulating the
      expression of different Trk receptors in DRG neurons through the PI3K/Akt and
      ERK1/2 signaling pathways.

PMID- 23142317
TI  - ALDH1B1 is a potential stem/progenitor marker for multiple pancreas progenitor
      pools.
AB  - Aldehyde dehydrogenase (ALDH) genes are increasingly associated with
      stem/progenitor cell status but their role in the maintenance of pluripotency
      remains uncertain. In a screen conducted for downstream Ngn3 target genes using
      ES derived pancreas progenitors we identified Aldh1b1, encoding a mitochondrial
      enzyme, as one of the genes strongly up regulated in response to Ngn3 expression.
      We found both by in situ hybridization and immunofluorescence using a specific
      antibody that ALDH1B1 is exclusively expressed in the emerging pancreatic buds of
      the early embryo (9.5 dpc) in a Pdx1 dependent manner. Around the time of
      secondary transition, ALDH1B1 expression was restricted in the tip tripotent
      progenitors of the branching epithelium and in a subset of the trunk epithelium.
      Expression in the latter was Ngn3 dependent. Subsequently, ALDH1B1 expression
      persisted only in the tip cells that become restricted to the exocrine lineage
      and declined rapidly as these cells mature. In the adult pancreas we identified
      rare ALDH1B1(+) cells that become abundant following pancreas injury in either
      the caerulein or streptozotocin paradigms. Blocking ALDH catalytic activity in
      pancreas embryonic explants resulted in reduced size of the explants and
      accelerated differentiation suggesting for the first time that ALDH activity may
      be necessary in the developing pancreas for the maintenance and expansion of
      progenitor pools.

PMID- 23142318
TI  - An enteral leucine supply modulates human duodenal mucosal proteome and decreases
      the expression of enzymes involved in fatty acid beta-oxidation.
AB  - Leucine is well known to regulate protein metabolism in muscle. We recently
      reported that enteral leucine infusion decreased proteasome activity in human
      duodenal mucosa and enhanced intestinal cell proliferation, but its effects on
      gut proteome remain unknown. Therefore, we aimed to assess the effects of an
      enteral leucine infusion on the whole proteome of duodenal mucosa. In this work,
      5 healthy volunteers received for 5h, on 2 occasions and in random order, an
      enteral supply of maltodextrins (0.25 g kg(-1) h(-1)) or maltodextrins
      supplemented with leucine (0.035 g kg(-1) h(-1)). At the end of infusion,
      endoscopic duodenal biopsy samples were collected and analyzed by 2D-PAGE. Eleven
      protein spots were differentially and significantly (P<0.05) expressed in
      response to the leucine-supplemented maltodextrins compared with maltodextrins
      alone. Forty percent of identified proteins by mass spectrometry were located in
      mitochondria. Four proteins were involved in lipid metabolism: HADHA, ACADVL and
      CPT2 expressions were reduced, whereas FABP1 expression was increased. In
      addition, the expression of DHA kinase involved in glycerol metabolism was also
      downregulated. Finally, leucine supplementation altered the duodenal mucosal
      proteome by regulating the expression of several enzymes mainly involved in lipid
      metabolism. These results suggest that leucine supplementation may slowdown fatty
      acid beta-oxidation in human duodenal mucosa.

PMID- 23142319
TI  - Inhibition of hepatitis C virus RNA translation by antisense bile acid conjugated
      phosphorothioate modified oligodeoxynucleotides (ODN).
AB  - BACKGROUND: The 5'-noncoding region (5'NCR) of the HCV-genome comprises an
      internal ribosome entry site essential for HCV-translation/replication.
      Phosphorothioate oligodeoxynucleotides (tS-ODN) complementary to this region can
      inhibit HCV-translation in vitro. In this study, bile acid conjugated tS-ODN were
      generated to increase cell-selective inhibition of 5'NCR-dependent HCV
      translation. METHODS: Different bile acid conjugated tS-ODN complementary to the
      HCV5'NCR were selected for their inhibitory potential in an in vitro
      transcription/translation assay. To analyze OATP (organic anion transporting
      polypeptides)-selective uptake of bile acid conjugated ODN, different hepatoma
      cells were stably transfected with the OATP1B1-transporter and primary human
      hepatocytes were used. An adenovirus encoding the HCV5'NCR fused to the
      luciferase gene (Ad-GFP-NCRluc) was generated to quantify 5'NCR-dependent HCV
      gene expression in OATP-overexpressing hepatoma cells and in vivo. RESULTS: A
      17mer phosphorothioate modified ODN (tS-ODN4_13) complementary to HCV5'NCR was
      able to inhibit 5'NCR-dependent HCV-translation in an in vitro
      transcription/translation test system by more than 90% and it was also effective
      in Huh7-cells containing the HCV subgenomic replicon. Conjugation to taurocholate
      (tS-ODN4_13T) significantly increased selective ODN uptake by primary human
      hepatocytes and by OATP1B1-expressing HepG2-cells compared to parental HepG2
      cells. Correspondingly, tS-ODN4_13T significantly inhibited HCV gene expression
      in liver-derived OATP1B1-expressing HepG2- or CCL13-cells up to 70% compared to
      unconjugated tS-ODN and compared to mismatch taurocholate coupled tS-ODN. In
      vivo, tS-ODN4_13T showed also a trend to block 5'NCR-dependent HCV gene
      expression. CONCLUSIONS: The tested taurocholate conjugated 17mer antisense ODN
      complementary to HCV5'NCV showed an increased and selective uptake by hepatocytes
      and liver-derived cells through OATP-mediated transport resulting in enhanced
      specific inhibition of HCV gene expression in vitro and in vivo. Thus, this novel
      approach may represent a promising strategy to improve antisense approaches with
      ODN in the control of hepatitis C infection.

PMID- 23142321
TI  - A practical post-modification synthesis of oligodeoxynucleotides containing 4,7
      diaminoimidazo[5',4':4,5]pyrido[2,3-d]pyrimidine nucleoside.
AB  - We describe herein the practical post-modification synthesis of
      oligodeoxynucleotides (ODNs) containing 4,7-diaminoimidazo[5',4':4,5]pyrido[2,3
      d]pyrimidine nucleoside (ImN(N)). Since the ImN(N) nucleoside unit possessing
      tribenzoyl groups on its exocyclic amino groups as the protecting group was quite
      unstable under acidic conditions, cleavage of its glycosidic linkage in ODN has
      been suggested throughout the conditions of solid-phase synthesis. As an
      alternative approach, we investigated a post-modification synthesis of the
      desired ODNs containing the ImN(N) unit. Starting with protected 4-amino-7-chloro
      1-(2-deoxy-beta-D-ribofuranosyl)imidazo[5',4':4,5]pyrido[2,3-d]pyrimidine
      derivative 1, conversion into the corresponding phosphoramidite unit was
      examined. The p-bromobenzoyl group (p-BrBz) was the best protecting group of 4
      amino group of 1 to give the phosphoramidite unit 9 for the post-modification
      synthesis. After carrying out the ODN synthesis linked to the controlled pore
      glass (CPG) support, the support was treated with ammonium hydroxide at 55 
      degrees C to remove the protecting groups, detach the ODN form the CPG support,
      and convert the 7-chloro group into a desired amino group. As a result, the
      desired ODNs containing ImN(N) were obtained in good yield.

PMID- 23142320
TI  - Optimization of thiazole analogues of resveratrol for induction of
      NAD(P)H:quinone reductase 1 (QR1).
AB  - NAD(P)H:quinone reductase 1 (QR1) belongs to a class of enzymes called
      cytoprotective enzymes. It exhibits its cancer protective activity mainly by
      inhibiting the formation of intracellular semiquinone radicals, and by generating
      alpha-tocopherolhydroquinone, which acts as a free radical scavenger. It is
      therefore believed that QR1 inducers can act as cancer chemopreventive agents.
      Resveratrol (1) is a naturally occurring stilbene derivative that requires a
      concentration of 21 MUM to double QR1 activity (CD = 21 MUM). The stilbene double
      bond of resveratrol was replaced with a thiadiazole ring and the phenols were
      eliminated to provide a more potent and selective derivative 2 (CD = 2.1 MUM).
      Optimizing the substitution pattern of the two phenyl rings and the central
      heterocyclic linker led to a highly potent and selective QR1 inducer 9o with a CD
      value of 0.087 MUM.

PMID- 23142322
TI  - Synthesis and cytotoxic activities of estrone and estradiol cis
      dichloroplatinum(II) complexes.
AB  - Sixteen platinum(II) complexes of estrone and estradiol were synthesized in this
      work to evaluate their cytotoxic activity against several cancer cell lines
      including estrogen dependent and independent ones. The synthesis of all the
      complexes was done in three steps. The reaction of steroids with dibromoalkanes
      was followed by a reaction of the bromoalkyl steroids with 2
      (aminomethyl)pyridine or 2-(2-aminoethyl)pyridine. The last step was a reaction
      of steroidal diamino ligands with potassium tetrachloroplatinate to obtain the
      desired platinum(II) complexes. Cytotoxicity assays showed that most of the
      complexes prepared are active against the cancer cell lines used-CEM, U-2 OS,
      MCF7, MCF7 AL, MDA-MB-468, BT-474, BT-549, and BJ fibroblasts. The six-membered
      platinum complexes are more active than five-membered ones.

PMID- 23142323
TI  - Synthesis and DNA interaction of ethylenediamine platinum(II) complexes linked to
      DNA intercalants.
AB  - A series of ethylenediamine platinum(II) complexes connected through semi-rigid
      chains of 1,2-bis(4-pyridyl)ethane to DNA intercalating subunits (naphthalene,
      anthracene or phenazine) has been synthesized, and their interactions with calf
      thymus (CT) DNA have been evaluated by viscometric titrations and equilibrium
      dialysis experiments. The parent ligands that contain anthracene or phenazine
      chromophores showed a monointercalative mode of DNA interaction (especially the
      anthracene derivative), with apparent association constants in the order of 10(4)
      M(-1). The corresponding platinum(II) complexes bind CT DNA through
      bisintercalation, as established by the significant increase of DNA contour
      length inferred from viscosity measurements, and the association constants are in
      the order of 10(5) M(-1). The naphthalene derivatives, however, exhibit a mixed
      mode of interaction, which suggests a partial contribution of both intercalation
      and groove binding for the ligand, and monointercalation in the case of the
      platinum(II) complex. Competition dialysis experiments carried out on the
      intercalative compounds have revealed a moderate selectivity towards GC DNA
      sequences for the derivatives containing the anthracene chromophore.

PMID- 23142324
TI  - Pancytopenia associated with influenza A infection.

PMID- 23142325
TI  - The role of mitochondria and biotransformation in abamectin-induced cytotoxicity
      in isolated rat hepatocytes.
AB  - Abamectin (ABA), which belongs to the family of avermectins, is used as a
      parasiticide; however, ABA poisoning can impair liver function. In a previous
      study using isolated rat liver mitochondria, we observed that ABA inhibited the
      activity of adenine nucleotide translocator and FoF1-ATPase. The aim of this
      study was to characterize the mechanism of ABA toxicity in isolated rat
      hepatocytes and to evaluate whether this effect is dependent on its metabolism.
      The toxicity of ABA was assessed by monitoring oxygen consumption and
      mitochondrial membrane potential, intracellular ATP concentration, cell
      viability, intracellular Ca(2+) homeostasis, release of cytochrome c, caspase 3
      activity and necrotic cell death. ABA reduces cellular respiration in cells
      energized with glutamate and malate or succinate. The hepatocytes that were
      previously incubated with proadifen, a cytochrome P450 inhibitor, are more
      sensitive to the compound as observed by a rapid decrease in the mitochondrial
      membrane potential accompanied by reductions in ATP concentration and cell
      viability and a disruption of intracellular Ca(2+) homeostasis followed by
      necrosis. Our results indicate that ABA biotransformation reduces its toxicity,
      and its toxic action is related to the inhibition of mitochondrial activity,
      which leads to decreased synthesis of ATP followed by cell death.

PMID- 23142326
TI  - Pineal and gonadal influences on ultradian locomotor rhythms of male Siberian
      hamsters.
AB  - The extent to which changes in ultradian and circadian rhythms (URs and CRs)
      reflect seasonal variations in pineal melatonin secretion was assessed in male
      Siberian hamsters transferred from long to short day lengths. The period of the
      locomotor activity UR increased from 2.5 h in long days to 4.5 h in short day
      lengths, but this and most other features of the short-day ultradian phenotype
      were unaffected by pinealectomy; only the short-day increase in UR amplitude was
      counteracted by pineal extirpation. Virtually all UR components were unaffected
      by gonadectomy or replacement testosterone or estradiol treatment; changes in
      testicular hormone secretion appear insufficient to account for seasonal
      fluctuation in URs. Pinealectomy did not affect activity onsets and offsets or
      phase angles of CR entrainment in short and long day lengths; the duration of
      nocturnal activity was equivalently longer in short than long days in both
      pinealectomized and pineal-intact hamsters. CR robustness of pinealectomized
      hamsters in short days was intermediate between values of long-day and short-day
      sham-pinealectomized males. Hourly nocturnal locomotor activity was markedly
      reduced in SD, and this effect was completely reversed by PINx. We conclude that
      seasonal transitions in UR and CR waveforms controlled by day length are mediated
      primarily by melatonin-independent mechanisms, with lesser contributions from
      melatonin-dependent processes. Most seasonal changes in ultradian and circadian
      rhythms in males of this species are not influenced by gonadal hormones. URs may
      allow animals to respond appropriately to changing environmental contingencies.
      In winter reduced activity combined with temporal restructuring of activity to
      include longer intervals of rest may be adaptive in maintaining body temperature
      at lower values and down-regulating energy expenditure when above ground
      temperatures are extremely low.

PMID- 23142327
TI  - Divergence in androgen sensitivity contributes to population differences in
      sexual dimorphism of electrocommunication behavior.
AB  - Weakly-electric fish (Apteronotidae) produce highly diverse electrocommunication
      signals. Electric organ discharges (EODs) vary across species, sexes, and in the
      magnitude and direction of their sexual dimorphism. Gonadal steroid hormones can
      modulate EODs, and differences in androgen sensitivity are hypothesized to
      underlie variation in the degree of sexual dimorphism across species. In this
      study, we asked whether variation in androgen sensitivity explained variation in
      sexual dimorphism of EODs within species, at the population level. We examined
      two populations of black ghost knifefish (Apteronotus albifrons), one from the
      Orinoco and the other from the Amazon River Basin. EOD frequency (EODf) and chirp
      rates were measured to characterize diversity in sexual dimorphism across
      populations. The magnitude of sexual dimorphism in EODf differed significantly
      across populations, and was more pronounced in the Orinoco population than in the
      Amazon population. Chirp rates were sexually monomorphic in both populations. 11
      Ketotestosterone (11-kT) was administered over a two-week period to assess
      population differences in sensitivity to androgens. 11-kT masculinized EODf
      significantly more in the population with the greater degree of sexual
      dimorphism. 11-kT had no effect on the sexually monomorphic chirping rates. We
      conclude that population divergence in androgen sensitivity contributes to
      variation in sexual dimorphism of EODf in A. albifrons.

PMID- 23142328
TI  - Mu-opioid receptor knockout mice are more sensitive to chlordiazepoxide-induced
      anxiolytic behavior.
AB  - We have previously demonstrated benzodiazepine binding in the cortex and
      hippocampus of mu-opioid receptor knockout (KO) mice. It is known that
      benzodiazepine receptors are involved in regulating anxiety-like behaviors. Thus,
      the present study was designed to examine whether there are changes in anxiety
      like behavior in mice lacking mu-opioid receptors. To produce anxiolytic activity
      (less anxiety), the prototype benzodiazepine receptor agonist chlordiazepoxide
      (CDP, 5 mg/kg) was intraperitoneally administered in wild type (WT) and mu-opioid
      receptor KO mice. We found that compared to WT mice, mu-opioid receptor KO mice
      showed enhanced anxiolytic activity to CDP, including increased number of entries
      into open arm, increased percentage of the time spent in open arms, and decreased
      percentage of the time spent in enclosed arms in the elevated plus-maze test. We
      also assessed protein expression of the gamma-aminobutyric acid (GABA) synthetic
      enzyme (glutamic acid decarboxylase; GAD). Western blotting data indicated that
      neither the lack of mu-opioid receptors nor CDP treatment altered cortical or
      hippocampal GAD65 or GAD67 protein expression. These data indicate that compared
      with WT, mu-opioid receptor KO mice experienced less anxiety and exhibited
      enhanced anxiolytic activity to CDP treatment, and these effects were not
      dependent on GAD65 or GAD67 protein expression. Our previous and present data
      suggest that the anxiolytic activity displayed in mu-opioid receptor KO mice is
      associated with upregulation of the benzodiazepine receptor system.

PMID- 23142329
TI  - Umbilical cord blood transplantation supported by third-party donor cells:
      rationale, results, and applications.
AB  - Low incidence of graft-versus-host disease provides the major rational for
      pursuing umbilical cord blood (UCB) stem cell transplantation (SCT). Considerable
      evidence also suggests a lower rate of recurrence after UCB SCT than after
      transplantation from adult donors. Recent advances in understanding of the human
      fetal immune development provide a rational underpinning for these clinical
      outcomes. The fetal immune system is geared toward maintaining tolerance to
      foreign antigens, particularly to the maternal antigens to which it is exposed
      throughout gestation. To this purpose it is dominated by a unique population of
      peripheral T regulatory cells that actively maintain tolerance. This and other
      features of the UCB lymphoid system explains the low incidence of graft-versus
      host disease and superior outcomes of UCB SCT with noninherited maternal antigen
      matched grafts. At the same time, highly sensitized maternal microchimeric cells
      are frequently detected in UCB and likely contribute to superior graft-versus
      leukemia effects and low rates of disease recurrence in inherited paternal
      antigen-matched UCB recipients. However, historically erratic and slow
      hematopoietic recovery after UCB SCT leads to increased early morbidity and
      mortality, excessive hospitalization, and increased costs. This has held up the
      widespread utilization of UCB SCT in adults. Here we summarize recent data on UCB
      SCT with an emphasis on studies of co-infusion of adult CD34 selected
      hematopoietic stem cells with UCB SCT. This procedure, through transient
      engraftment of adult hematopoietic stem cells, largely overcomes the problem of
      delayed engraftment. It also results in predictable engraftment of a UCB with the
      desired characteristics. We also briefly discuss unresolved issues and possible
      future applications of this technology.

PMID- 23142330
TI  - Bortezomib plus dexamethasone followed by escalating donor lymphocyte infusions
      for patients with multiple myeloma relapsing or progressing after allogeneic stem
      cell transplantation.
AB  - Multiple myeloma relapsing after allogeneic stem cell transplantation (alloSCT)
      has a poor outcome. To assess the safety and efficacy of bortezomib and
      dexamethasone (VD) combination followed by donor lymphocyte infusions (DLIs) in
      myeloma patients relapsing or progressing after alloSCT, a prospective phase II
      study was designed. The treatment plan consisted of three VD courses followed by
      escalated doses of DLIs in case of response or at least stable disease. Nineteen
      patients were enrolled with a median age of 57 years (range, 33 to 67); 14
      patients were allografted from human leukocyte antigen-identical siblings and 5
      from alternative donors. Sixteen of 19 patients received the planned treatment,
      but 3 patients did not: 2 patients because of disease progression and 1 refused.
      After the VD phase the response rate was 62%, with 1 complete remission, 6 very
      good partial remissions, 5 partial remissions, 2 patients with stable disease,
      and 5 with progressive disease. After the DLI phase, the response rate was 68%,
      but a significant upgrade of response was observed: 3 stringent complete
      remissions, 2 complete remissions, 5 very good partial remissions, 1 partial
      remission, 4 with stable disease, and 1 with progressive disease. With a median
      follow-up of 40 months (range, 29 to 68), the 3-year progression-free survival
      and overall survival rates were 31% and 73%, respectively. Neither unexpected
      organ toxicities, in particular severe neuropathy, nor severe acute graft-versus
      host disease flares were observed. VD-DLIs is a safe treatment for multiple
      myeloma patients relapsing or progressing after alloSCT and may be effective.

PMID- 23142331
TI  - Endoscopic management of complications after gastrointestinal weight loss
      surgery.
AB  - As more patients undergo bariatric surgery, gastroenterologists will increasingly
      encounter variant postsurgical anatomies and postoperative complications. We
      discuss the diagnosis and management of bleeding, ulcers, foreign bodies,
      stenoses, leaks, fistulas, pancreaticobiliary diseases, weight regain, and
      dilated outlets.

PMID- 23142332
TI  - Discordance among transient elastography, aspartate aminotransferase to platelet
      ratio index, and histologic assessments of liver fibrosis in patients with
      chronic hepatitis C.
AB  - BACKGROUND & AIMS: Liver biopsy is the standard for assessing hepatic fibrosis.
      Ultrasound transient elastography (TE) and the aspartate aminotransferase to
      platelet ratio index (APRI) are validated, noninvasive tests for identifying
      patients with cirrhosis. We evaluated discordance among TE, APRI, and histology
      diagnoses of cirrhosis. METHODS: We analyzed findings from 109 patients with
      chronic hepatitis C who underwent TE within 6 months of liver biopsy at the US
      National Institutes of Health from 2006 to 2011. Fibrosis was scored using the
      Ishak scale (0-6). APRI scores were calculated using data collected on the day of
      the biopsy. Area under receiver operator characteristic curves for TE and APRI
      were calculated to distinguish patients with cirrhosis (Ishak scores, 5-6) from
      those without cirrhosis (Ishak scores, 0-4). The best cut-off value and
      corresponding positive predictive value (PPV) and negative predictive value (NPV)
      were selected. RESULTS: Based on biopsy analysis, 18% of the patients had no
      fibrosis, 52% had mild fibrosis, 17% had bridging fibrosis, and 13% had
      cirrhosis. A TE cut-off value of 13.1 kPa identified patients with cirrhosis with
      the highest level of accuracy (100% sensitivity, 89% specificity, 58% PPV, 100%
      NPV), as did an APRI cut-off value of 1.0 (79% sensitivity, 78% specificity, 34%
      PPV, 96% NPV). Results from TE and APRI were discordant for 28% of cases. TE
      identified all cases of cirrhosis and an additional 10 patients who were not
      found to have cirrhosis based on histology analysis; 7 of these patients had
      clinical or radiologic evidence of cirrhosis, indicating that the biopsy sample
      was not staged correctly. CONCLUSIONS: TE increases the accuracies of biopsy and
      APRI analyses in identifying patients with cirrhosis. TE also might be used to
      screen patients for cirrhosis and identify those who should be followed up for
      development of hepatocellular carcinoma and varices.

PMID- 23142333
TI  - Where have you been all my life?: A laparotomy in infancy indicated the patient
      had no uterus or ovaries in her peritoneal cavity.

PMID- 23142334
TI  - Bone density, bone quality, and FRAX: changing concepts in osteoporosis
      management.
AB  - Bone densitometry was originally developed to diagnose a high risk for fragility
      fractures in older postmenopausal women who may have primary osteoporosis. Its
      widespread availability, however, has led to its use in healthy peri- and
      premenopausal patients and the unexpected findings of low bone density in this
      group of patients. Their low bone density caused much uncertainty about the
      likelihood of fracture risk and what treatment might be needed. Conceptually,
      bone density reflected bone strength, and so a low density reflected increased
      fracture risk. Clinical experience and the results of pivotal studies of therapy
      for osteoporosis suggested that bone density was only partly responsible for
      skeletal strength. Many structural and material properties of bone, not measured
      by bone density, made it resist fracturing. Clinical risk factors helped
      determine these characteristics, albeit imperfectly, and aided clinicians decide
      whether and what treatment was needed. But now, new fracture risk assessment
      protocols (namely, FRAX, the WHO risk assessment tool) are available to help
      resolve this dilemma. This paper reviews some of the clinical observations that
      led to rethinking the concept bone density and bone strength and how it changes
      the clinical approach to therapy for the healthy young patient.

PMID- 23142335
TI  - Diffusion measures in early stage parkinsonism: controversial findings including
      hemispheric lateralisation.

PMID- 23142336
TI  - (234)U/(238)U signatures associated with uranium ore bodies: part 3 Koongarra.
AB  - The Koongarra ore body is an early Proterozoic U ore body in the Alligator Rivers
      U province, Northern Territory, Australia. It has surface expression with a redox
      front located ~30 m below the surface. The (234)U/(238)U activity ratios (AR) for
      the ground water and the amorphous phase of the solid have been analysed for the
      ore zone and dispersion halo as a function of depth. The results display a
      (234)U/(238)U AR signature with depth which may be common to all U ore bodies.
      The (234)U/(238)U AR is depressed below secular equilibrium in the weathered
      material above the redox front; rises significantly above secular equilibrium in
      the vicinity of the redox front; and is followed by a gradual decrease with depth
      below the redox front. The amplitude of the profile is a function of local
      conditions. A model is proposed for the signature in which oxidising waters
      preferentially leach the (234)U sites at the redox front due to preconditioning
      of the (234)U sites by alpha recoil during the decay of (23)(8)U to (23)(4)U.
      Mass balance requires the solid material left behind the redox front to have a
      (234)U/(238)U AR reduced below 1. Local second order effects may be superimposed
      on the signature. The signature may have application to calibrating scenarios for
      nuclear waste repositories, assisting in understanding historical climates,
      economic evaluation of U ore bodies and U exploration.

PMID- 23142337
TI  - Expression characteristics of astrocyte elevated gene-1 (AEG-1) in tongue
      carcinoma and its correlation with poor prognosis.
AB  - Astrocyte elevated gene-1 (AEG-1) expression is increased in diverse human
      cancers and plays a vital role in tumorigenesis and progression. The aim of this
      study was to investigate the clinicopathologic features and prognostic
      significance of AEG-1 in squamous cell carcinoma of the tongue (TSCC).
      Immunohistochemistry (IHC) was performed to examine AEG-1 protein expression in
      paraffin-embedded tissues from 93 patients with TSCC. Real-time PCR and western
      blot analyses were employed to examine AEG-1 expression in 4 pairs of primary
      TSCC and adjacent non-cancerous tissues from the same patient.
      Immunohistochemical results revealed that the positive rate for AEG-1 in TSCC
      tissues (48.39%, 45/93) was higher than that in the normal tongue tissues
      (10.00%, 3/30) (P < 0.001). These results were further confirmed between TSCC
      tissues and matched adjacent non-cancerous tissues by Western blot and RT-PCR.
      Simultaneously, AEG-1 protein level was positively correlated with
      differentiation degree (P < 0.001), clinical stage (P < 0.001), T classification
      (P = 0.007) and N classification (P = 0.012). Furthermore, patients with higher
      AEG-1 expression had shorter overall survival time. Multivariate analysis (Cox
      regression) also suggested that AEG-1 expression was an independent prognostic
      indicator for TSCC (P = 0.043). Our results indicate that AEG-1 expression is
      closely associated with carcinogenesis and progression of TSCC, and may represent
      a novel and valuable predictor for prognostic evaluation of TSCC patients.

PMID- 23142338
TI  - Breast cancer detection risk in screening mammography after a false-positive
      result.
AB  - BACKGROUND: False-positives are a major concern in breast cancer screening.
      However, false-positives have been little evaluated as a prognostic factor for
      cancer detection. Our aim was to evaluate the association of false-positive
      results with the cancer detection risk in subsequent screening participations
      over a 17-year period. METHODS: This is a retrospective cohort study of 762,506
      women aged 45-69 years, with at least two screening participations, who underwent
      2,594,146 screening mammograms from 1990 to 2006. Multilevel discrete-time hazard
      models were used to estimate the adjusted odds ratios (OR) of breast cancer
      detection in subsequent screening participations in women with false-positive
      results. RESULTS: False-positives involving a fine-needle aspiration cytology or
      a biopsy had a higher cancer detection risk than those involving additional
      imaging procedures alone (OR = 2.69; 95%CI: 2.28-3.16 and OR = 1.81; 95%CI: 1.70
      1.94, respectively). The risk of cancer detection increased substantially if
      women with cytology or biopsy had a familial history of breast cancer (OR = 4.64;
      95%CI: 3.23-6.66). Other factors associated with an increased cancer detection
      risk were age 65-69 years (OR = 1.84; 95%CI: 1.67-2.03), non-attendance at the
      previous screening invitation (OR = 1.26; 95%CI: 1.11-1.43), and having undergone
      a previous benign biopsy outside the screening program (OR = 1.24; 95%CI: 1.13
      1.35). CONCLUSION: Women with a false-positive test have an increased risk of
      cancer detection in subsequent screening participations, especially those with a
      false-positive result involving cytology or biopsy. Understanding the factors
      behind this association could provide valuable information to increase the
      effectiveness of breast cancer screening.

PMID- 23142340
TI  - An improved quantitative method to assess adhesive properties of Trichomonas
      vaginalis to host vaginal ectocervical cells using flow cytometry.
AB  - Microbial adhesion is a critical step for infection and colonization of the host.
      Trichomonas vaginalis, a human urogenital extracellular parasite, relies on host
      cell adhesion for infection and pathogenesis. Although host cell adhesion of T.
      vaginalis is strain-dependent and it may be influenced by many environmental
      factors, a technical limitation to quantify T. vaginalis adhesion falls upon a
      laborious and time-consuming protocol of fluorescent microscopy. This technical
      limitation reduces the ability of screening multiple parameters or detecting
      multiple cell types simultaneously. Here we tested the capability of using flow
      cytometry as a qualitative and quantitative method to measure adhesion of this
      human infectious microorganism to vaginal ectocervical cells. Various strains of
      T. vaginalis with different adhesion properties were stained with CellTracker
      Orange (CMTMR) prior to incubation with host cells. Analyses by flow cytometry
      revealed that adhered CMTMR-stained parasites were clearly distinguishable from
      the host cells and also enabled absolute cell counts to be determined. This
      method was validated with the comparison of parasite strains that display
      variable degrees of host cell adhesion. This assay can now be applied to test
      many variables and environmental factors simultaneously that may affect T.
      vaginalis adhesion.

PMID- 23142341
TI  - A multiplex-PCR assay for identification of the quarantine plant pathogen
      Xanthomonas axonopodis pv. phaseoli.
AB  - In this study we developed an algorithm to screen for all exact molecular
      signatures of the quarantine pathogen Xanthomonas axonopodis pv. phaseoli (Xap),
      based on available data of the presence or absence of virulence-associated genes.
      The simultaneous presence of genes avrBsT and xopL is specific to Xap. Therefore
      we developed a multiplex PCR assay targeting avrBsT and xopL for the molecular
      identification of Xap. The specificity of this multiplex was validated by
      comparison to that of other molecular identification assays aimed at Xap, on a
      wide collection of reference strains. This multiplex was further validated on a
      blind collection of Xanthomonas isolates for which pathogenicity was assayed by
      stem wounding and by dipping leaves into calibrated inocula. This multiplex was
      combined to the previously described X4c/X4e molecular identification assay for
      Xap. Such a combination enables the molecular identification of all strains of
      Xanthomonas pathogenic on bean. Results also show that assay by stem wounding
      does not give reliable results in the case of Xap, and that pathogenicity assays
      by dipping should be preferred.

PMID- 23142339
TI  - Progesterone-estrogen interactions in synaptic plasticity and neuroprotection.
AB  - 17beta-Estradiol and progesterone exert a number of physiological effects
      throughout the brain due to interactions with several types of receptors
      belonging to the traditional family of intracellular hormonal receptors as well
      as to membrane-bound receptors. In particular, both hormones elicit rapid
      modifications of neuronal excitability that have been postulated to underlie
      their effects on synaptic plasticity and learning and memory. Likewise, both
      hormones have been shown to be neuroprotective under certain conditions, possibly
      due to the activation of pro-survival pathways and the inhibition of pro
      apoptotic cascades. Because of the similarities in their cellular effects, there
      have been a number of questions raised by numerous observations that progesterone
      inhibits the effects of estrogen. In this manuscript, we first review the
      interactions between 17beta-estradiol (E2) and progesterone (P4) in synaptic
      plasticity, and conclude that, while E2 exerts a clear and important role in long
      term potentiation of synaptic transmission in hippocampal neurons, the role of P4
      is much less clear, and could be accounted by the direct or indirect regulation
      of GABAA receptors. We then discuss the neuroprotective roles of both hormones,
      in particular against excitotoxicity. In this case, the neuroprotective effects
      of these hormones are very similar to those of the neurotrophic factor BDNF.
      Interestingly, P4 antagonizes the effects of E2, possibly through the regulation
      of estrogen receptors or of proteins associated with the receptors or
      interactions with signaling pathways activated by E2. Overall, this review
      emphasizes the existence of common molecules and pathways that participate in the
      regulation of both synaptic plasticity and neurodegeneration.

PMID- 23142342
TI  - Developments in autotransplantation of teeth.
AB  - Transplantation of teeth has been done for hundreds of years. In the late 18th
      and early 19th century transplants of teeth between individuals were relatively
      common at specialist dental practices in London. Surprisingly tooth
      allotransplants have been found to last 6 years on average. In Scandinavia during
      the 1950 and 1960's autotransplantation of teeth began to be carried out under
      increasingly controlled conditions. These have proved to be very successful in
      long term studies with autotransplants surviving up to 45 years post-surgery.
      Recent developments in cone beam CT and rapid 3D prototyping have enabled the
      fabrication of accurate surgical templates which can be used to prepare the
      recipient site immediately prior to transplantation. This has resulted in a
      drastically reduced extra-oral time for the transplant teeth which can be
      expected to improve success rates further. Autotransplants provide significant
      advantages compared to single tooth implants and should be considered the
      treatment of choice in the growing child.

PMID- 23142343
TI  - Pacemaker-detected atrial fibrillation in patients with pacemakers: prevalence,
      predictors, and current use of oral anticoagulation.
AB  - BACKGROUND: Dual-chamber pacemakers frequently document atrial fibrillation (AF)
      in patients without symptoms. Pacemaker-detected AF is associated with a 2.5-fold
      increased risk of stroke, although it is not established whether oral
      anticoagulation reduces this risk. This study sought to determine the prevalence
      and predictors of pacemaker-detected AF and to document current oral
      anticoagulant use. METHODS: A retrospective analysis included all patients from a
      single academic hospital who had pacemakers capable of documenting AF. Blinded
      evaluation of all echocardiograms conducted within 6 months of implantation was
      performed. RESULTS: Of 445 patients, pacemaker-detected AF was present in 246
      (55.3%), who were older (74.3 +/- 13.7 years vs 71.7 +/- 14.4, P = 0.046), more
      likely to have a history of clinical AF (29.7% vs 19.1%, P = 0.01), and had a
      larger left atrial volume index (34.4 +/- 11.8 mL/m(2) vs 30.0 +/- 9.9 mL/m(2), P
      = 0.019) than the patients without pacemaker-detected AF. Among patients without
      a clinical history of AF, left atrial volume index was higher among those with
      pacemaker-detected AF (33.7 +/- 11.3 mL/m(2) vs 29.0 +/- 10.1 mL/m(2), P =
      0.034). Anticoagulants were used in 35.3% of patients with pacemaker-detected AF,
      compared with 21.6% of patients without (P < 0.05). In patients with pacemaker
      detected AF, anticoagulants were used more frequently among patients who also had
      clinical AF (58.9%) compared with those without (23.7%, P < 0.001). CONCLUSIONS:
      Pacemaker-detected AF occurs in 50% of pacemaker patients and is treated with
      anticoagulants in less than 25% of patients who do not have a history of clinical
      AF. Clinical trials are needed to determine the role of anticoagulation in this
      population.

PMID- 23142344
TI  - Does preoperative atrial fibrillation portend a poorer prognosis in patients
      undergoing isolated aortic valve replacement? A multicentre Australian study.
AB  - BACKGROUND: Preoperative atrial fibrillation (preop-AF) has been associated with
      poorer early and late outcomes after cardiac surgery. Few studies, however, have
      evaluated the impact of preop-AF on early and late outcomes after isolated aortic
      valve replacement (AVR). METHODS: Data obtained prospectively between June 2001
      and December 2009 by the Australian and New Zealand Society of Cardiac and
      Thoracic Surgeons National Cardiac Surgery Database Program was retrospectively
      analyzed. Patients who underwent concomitant atrial arrhythmia surgery/ablation
      were excluded. Demographic and operative data were compared between patients
      undergoing isolated AVR who presented with preop-AF and those in sinus rhythm.
      The independent effect of preop-AF on 12 short-term complications and long-term
      survival was determined using binary logistic and cox regression, respectively.
      RESULTS: Isolated AVR surgery was performed in 2789 patients; 380 (13.6%)
      presented with preop-AF. Preop-AF patients were generally older (mean age, 73 vs
      68 years; P < 0.001) and presented more often with comorbidities including
      congestive heart failure, diabetes, and cerebrovascular disease (all P < 0.05).
      There was a trend toward increased 30-day mortality in patients with preop-AF on
      multivariate analysis (P = 0.051). The incidence of early complications was
      similar in both groups on multivariate analysis (P > 0.05). Preop-AF was
      independently associated with reduced long-term survival (hazard ratio, 1.36; 95%
      confidence interval, 1.01-1.83; P = 0.041). CONCLUSIONS: Preop-AF is associated
      with an increased risk of late mortality after isolated AVR. As such, concomitant
      atrial ablation with AVR should be prospectively studied.

PMID- 23142345
TI  - Circulating proangiogenic progenitor cells independently predict functional
      capacity in heart failure patients.
AB  - BACKGROUND: Endothelial dysfunction is an important underlying mechanism in the
      pathophysiology of heart failure (HF). Circulating proangiogenic progenitor cells
      (CPCs) are endothelial and hematopoietic progenitor cells involved in the process
      of vasculogenesis repairing damaged and dysfunctional endothelium. Our aim was to
      evaluate whether an independent association exists between CPCs and functional
      capacity in HF patients. METHODS: This cross-sectional study included 121
      ambulatory HF patients with reduced left ventricular ejection fraction seen at a
      single institution. We analyzed the association between CPCs, measured as
      circulating CD34+VEGFR2+ cells and early outgrowth colony forming units (EO
      CFUs), and patients' functional capacity measured as peak oxygen consumption
      (VO2). RESULTS: The mean age was 55 +/- 11 years; 96 patients (79%) were male.
      Forty-three patients (36%) had ischemic cardiomyopathy. Patients were taking
      optimal HF therapy (96% taking beta-blockers, 91% taking renin-angiotensin
      inhibitors, and 60% had an implanted internal cardiac defibrillator). In
      univariate analyses, CD34+VEGFR2+ cells were inversely associated with peak VO2
      (P = 0.02) while EO-CFUs showed a positive association with peak VO2 (P < 0.01).
      These associations persisted after adjusting for sex, New York Heart Association
      class, body mass index, diabetes, cardiac resynchronization therapy, ischemic
      cardiomyopathy and b-type natriuretic peptide levels. CONCLUSIONS: Cultured EO
      CFUs may represent a measure of functional capacity and vasculogenesis potential
      while CD34+VEGFR2+ cells represent the mobilized cells in response to endothelial
      damage. Our study suggests that lower EO-CFUs (worse cell function) and higher
      CD34+VEGFR2+ cells are associated with poorer functional capacity.

PMID- 23142346
TI  - Structural mechanisms of allostery and autoinhibition in JNK family kinases.
AB  - c-Jun N-terminal (JNK) family kinases have a common peptide-docking site used by
      upstream activating kinases, substrates, scaffold proteins, and phosphatases,
      where the ensemble of bound proteins determines signaling output. Although there
      are many JNK structures, little is known about mechanisms of allosteric
      regulation between the catalytic and peptide-binding sites, and the activation
      loop, whose phosphorylation is required for catalytic activity. Here, we compare
      three structures of unliganded JNK3 bound to different peptides. These were
      compared as a class to structures that differ in binding of peptide, small
      molecule ligand, or conformation of the kinase activation loop. Peptide binding
      induced an inhibitory interlobe conformer that was reversed by alterations in the
      activation loop. Structure class analysis revealed the subtle structural
      mechanisms for allosteric signaling between the peptide-binding site and
      activation loop. Biochemical data from isothermal calorimetry, fluorescence
      energy transfer, and enzyme inhibition demonstrated affinity differences among
      the three peptides that were consistent with structural observations.

PMID- 23142347
TI  - Crystal structure of the human ecto-5'-nucleotidase (CD73): insights into the
      regulation of purinergic signaling.
AB  - In vertebrates ecto-5'-nucleotidase (e5NT) catalyzes the hydrolysis of
      extracellular AMP to adenosine and represents the major control point for
      extracellular adenosine levels. Due to its pivotal role for activation of P1
      adenosine receptors, e5NT has emerged as an appealing drug target for treatment
      of inflammation, chronic pain, hypoxia, and cancer. Crystal structures of the
      dimeric human e5NT reveal an extensive 114 degrees  conformational switch between
      the open and closed forms of the enzyme. The dimerization interface is formed by
      the C-terminal domains and exhibits interchain motions of up to 13 degrees .
      Complex structures with adenosine and AMPCP indicate that structural control of
      the domain movement determines the selectivity for monophosphate nucleotides.
      Binding modes of nucleotide-derived and flavonoid-based compounds complexed to
      the C-terminal domain in the open form reveal an additional binding pocket of
      ~210 A(3) that might be explored to design more potent inhibitors.

PMID- 23142348
TI  - Action blind: disturbed self-other integration in schizophrenia.
AB  - Recent research using individual task settings suggests that a major problem in
      schizophrenia is a dysfunctional theory of mind system leading to false mental
      state attributions. However, if a more low-level deficit to integrate own and
      other's actions (action blindness) is present in schizophrenia is still unknown.
      Using a social Simon task, we tested if schizophrenia patients have a deficit in
      self-other integration. Further, we tested for a possible genetic bias of this
      dysfunction by studying clinically unaffected first-degree relatives of
      schizophrenia patients. While schizophrenia patients showed no Social Simon
      effect, we found a reliable social Simon effect in healthy participants and first
      degree relatives of schizophrenia patients. Joint task performance differed
      statistically between patients and healthy controls. We did not find any
      differences in the size of the social Simon effects of relatives and healthy
      controls. The present findings suggest that schizophrenia patients have severe
      problems with self-other integration, which may lead to problems in social
      interactions. Since first-degree relatives of schizophrenia patients showed a
      reliable social Simon effect, the evidence for a genetic bias of this social
      dysfunction in schizophrenia however is weak.

PMID- 23142349
TI  - Line bisection error predicts the presence and severity of neglect dyslexia in
      paragraph reading.
AB  - Cancellation tasks and line bisection tasks are commonly used to diagnose spatial
      neglect after right hemisphere lesions. In such tasks, neglect patients often
      show leftsided omissions of targets in cancellation tests as well as a
      pathological rightward deviation in horizontal line bisection. However, double
      dissociations have also been reported and the relation between performance in
      both tasks is not clear. Another impairment frequently associated with the
      neglect syndrome are omissions or misread initial letters of single words, a
      phenomenon termed neglect dyslexia (ND). Omissions of whole words on the
      contralesional side of the page are generally considered as egocentric or space
      based errors, whereas misreadings of the left part of a word in ND can be viewed
      as a type of stimulus-centered or word-based, perceptual error. As words,
      sentences and horizontal lines have a similar spatial layout in the sense that
      they all are horizontally aligned, long stimuli with a canonical left-right
      orientation (with a defined beginning on the left and an end on the right side),
      we hypothesized a significant association between the horizontal line bisection
      error (LBE) in neglect and the extent (number) of neglected or substituted
      letters within single words in ND (neglect dyslexia extension, NDE). To this
      purpose, we computed Center-of-Cancellation (CoC) scores in a cancellation task
      as well as Center-of-Reading (CoR) scores in an experimental paragraph reading
      test. We found that the CoR was a better indicator for egocentric word omissions
      than the CoC in a group of 17 patients with left visuospatial neglect.
      Furthermore, the LBE predicted the severity of ND, indicated by highly
      significant correlations between the LBE and the extent of the neglected letter
      string within single words (NDE; r=0.73, p<0.001) as well as between the LBE and
      the frequency of ND errors (r=0.61; p=0.009). In contrast, we found no
      significant correlation between the CoC and the severity of ND. These results
      indicate two different pathological mechanisms being responsible for
      contralesional spatial neglect and ND. In conclusion, the LBE is a more sensitive
      predictor of the presence and severity of the reading disorder in spatial neglect
      than conventional cancellation tasks.

PMID- 23142350
TI  - Processing polarity: ERP evidence for differences between positive and negative
      polarity.
AB  - The goal of the present study was to investigate event-related potential (ERP)
      responses to Dutch negative and positive polarity adverbs of degree presented in
      licensed and unlicensed contexts with negative and affirmative particles directly
      preceding the polarity item. To control for effects of the processing of negation
      as such, neutral adverbs were also presented in negative and affirmative
      contexts. The results did not show any significant effect of negation for the non
      polar adverbs, allowing context effects for polarity items to be interpreted as
      being due to the appropriateness of the context. Negative polarity violations
      elicited an N400 response that might reflect the lack of semantic congruity of
      the negative polarity item in an affirmative context. In contrast, processing
      positive polarity items in context of negation resulted in a positive effect
      resembling the P600, which may be considered as a marker of a different sort of
      integration difficulty caused by violation of licensing conditions and/or a
      search for a licensor in the wider discourse context. The study presented here is
      the first to show an unambiguous dissociation between responses to negative and
      positive polarity violations. This dissociation argues for different mechanisms
      underlying the processing of these two types of polarity; we propose that
      positive polarity items are sensitive to wider discourse context, while negative
      polarity items are more sensitive to local lexical context.

PMID- 23142351
TI  - Adaptive tuning of perceptual timing to whole body motion.
AB  - In a previous work we have shown that sinusoidal whole-body rotations producing
      continuous vestibular stimulation, affected the timing of motor responses as
      assessed with a paced finger tapping (PFT) task (Binetti et al. (2010).
      Neuropsychologia, 48(6), 1842-1852). Here, in two new psychophysical experiments,
      one purely perceptual and one with both sensory and motor components, we explored
      the relationship between body motion/vestibular stimulation and perceived timing
      of acoustic events. In experiment 1, participants were required to discriminate
      sequences of acoustic tones endowed with different degrees of acceleration or
      deceleration. In this experiment we found that a tone sequence presented during
      acceleratory whole-body rotations required a progressive increase in rate in
      order to be considered temporally regular, consistent with the idea of an
      increase in "clock" frequency and of an overestimation of time. In experiment 2
      participants produced self-paced taps, which entailed an acoustic feedback. We
      found that tapping frequency in this task was affected by periodic motion by
      means of anticipatory and congruent (in-phase) fluctuations irrespective of the
      self-generated sensory feedback. On the other hand, synchronizing taps to an
      external rhythm determined a completely opposite modulation (delayed/counter
      phase). Overall this study shows that body displacements "remap" our metric of
      time, affecting not only motor output but also sensory input.

PMID- 23142352
TI  - Nitric oxide mediates the antihypertensive and vascular relaxing effects of a
      soluble cocoa fiber product in spontaneously hypertensive rats.
AB  - The involvement of endothelial-relaxing factors on the vascular and
      antihypertensive effects of a cocoa fiber product (CFP) obtained from cocoa husks
      was studied. We carried out in vitro experiments with aorta rings from untreated
      spontaneously hypertensive rats (SHR) and in vivo experiments with SHR. CFP did
      not relax the endothelium denuded aorta rings and N(W)-nitro-l-arginine methyl
      ester (l-NAME) partially blocked the vascular relaxing and antihypertensive
      effects of CFP. Nevertheless, indomethacin did not modify these effects. Nitric
      oxide mediates therefore the antihypertensive and aorta relaxing effects of CFP
      in SHR.

PMID- 23142353
TI  - [Management of uncomplicated pelvic inflammatory disease].
AB  - Since the 1993 French consensus conference on uncomplicated pelvic inflammatory
      diseases (uPID), new antibiotics appeared and bacterial resistances did evoluate.
      This methodic analysis of the literature updates different aspects of its
      treatment. Antibiotherapy must be established early (EL3). Inpatient and
      intravenous treatment is not superior to outpatient and oral treatment (EL1).
      Ofloxacine+metronidazole association can be proposed in first intention (EL1). If
      case of Neisseria gonorrhoeae infection, one ceftriaxone injection must be
      associated (EL4). All the other antibiotics associations have shown to be
      efficient except the metronidazole+doxycycline association, which is not
      indicated (EL2). Two weeks treatment seems to be a sufficient duration.
      Laparoscopic treatment in first intention is not justified except for diagnostic
      doubts or unfavorable evolution of the medical treatment (EL4). Neither non
      steroidic antiinflamatorries, nor corticosteroids, have been proved to be
      efficient to decrease the adherence risk in uPID (EL3). Early extraction of an
      intra uterine device (IUD) allows symptomatologic improvement (EL2). Partners
      treatment with azithromycin improves the 4 months bacteriologic results (EL2).
      HIV positive patients do not need specific treatment (EL3).

PMID- 23142354
TI  - [Prophylactic antibiotics and intrauterine procedures].
AB  - Prophylactic antibiotics (PA) are effective to prevent post hysterosalpingography
      pelvic inflammatory disease (PID) and should be performed in these patients. No
      advantages are reported concerning PA in patients undergoing intra uterine device
      placement, hysteroscopy (diagnosis or operative hysteroscopy), medical abortion
      or uterine revision. Systematic PA with tetracyclins or imadazols is effective to
      prevent post abortion PID in patients undergoing surgical abortion and should be
      performed in these patients.

PMID- 23142355
TI  - [Pelvic inflammatory diseases].

PMID- 23142356
TI  - [Predictive factors for vaginal birth after cesarean section].
AB  - OBJECTIVES: Determination of predictive factors of vaginal delivery in women with
      a history of caesarean section undergoing a trial of labor. MATERIALS AND
      METHODS: Relevant studies were identified through Medline, and the Cochrane
      databases 1980-2012. Recommendations from the French and foreign obstetrical
      societies or colleges have been consulted. RESULTS: In France in 2010, a trial of
      labor was attempted in 49 % with 75 % successful rate (EL2). The site of delivery
      does not appear to influence the rate of successful trial of labor (EL3). Two
      factors are strongly associated with vaginal birth after caesarean (VBAC): prior
      history of vaginal delivery and spontaneous labor (EL2). Many factors appear to
      decrease the rate of VBAC: maternal age above 40 years (EL3), body mass index
      greater than 30 kg/m(2) (EL3), birth weights greater than 4000 g (EL3),
      unfortunately, prediction of macrosomia seems to be inaccurate. Induction of
      labor with pharmacological (prostaglandins and oxytocin) and mechanical methods
      (Foley catheter) decreased rate of successful VBAC (EL2). The use of pelvimetry
      to accept or avoid trial of labor, increase the risk of elective caesarean
      section (EL2) and should therefore not be recommended (grade C). Nomograms are
      not accurate to predict fail trial of labor as its clinical relevance is limited
      and has not yet evaluated in French population (expert opinion). CONCLUSION:
      After caesarean, trial of labor is associated with 75 % successful rate. Two
      factors are strongly associated with VBAC: a prior history of vaginal delivery
      and spontaneous labor.

PMID- 23142357
TI  - [Pelvic inflammatory diseases - introduction].

PMID- 23142358
TI  - [Induction of labor and intrapartum management for women with uterine scar].
AB  - OBJECTIVES: To evaluate the benefits and risks of labor induction in patients
      previously delivered by at least one low transverse cesarean section. To define
      how labor should be managed in patients attempting a vaginal birth after cesarean
      section (VBAC). METHODS: A literature search was performed using the Pubmed((r))
      and Cochrane((r)) databases. Foreign societies guidelines were also consulted.
      RESULTS: Labor induction is associated with an increased risk of uterine rupture
      that could be estimated at 1% with oxytocine and 2% with vaginal prostaglandins
      (Level 2). Mechanical methods have been insufficiently studied. Misoprostol seems
      to dramatically increase the risk of uterine rupture (Level 3). The routine use
      of intrauterine pressure catheter does not prevent uterine rupture (Professional
      agreement). A moderate increase of uterine rupture was also found with
      augmentation (Level 3). The risk of uterine rupture increases when cervical
      dilatation is arrested for 3 hours or more when a good uterine dynamic is
      obtained (Professional agreement). The use of epidural analgesia should be
      encouraged (Grade C). Routine digital exploration of the uterine scare postpartum
      is not necessary (Grade C). CONCLUSION: Women attempting a VBAC should be aware
      of the modalities of labor management. When labor induction is warranted, women
      should also be informed of the indication and the increased risk of uterine
      rupture. The choice of labor induction method should take into consideration
      maternal and obstetrical characteristics.

PMID- 23142359
TI  - [Specific particularities of uterine scars and their impact on the risk of
      uterine rupture in case of trial of labor].
AB  - OBJECTIVE: To assess the risk of uterine rupture in case of uterine scar in
      specific situations. To investigate whether ultrasonographic measurement of the
      lower uterine segment is predictive of the risk of uterine rupture. METHODS:
      French and English publications were identified through PubMed and Cochrane
      databases. RESULTS: Trial of labor after cesarean (TOLAC) is possible in cases of
      uterine mullerian anomalies, segmental vertical or unknown uterine incision,
      postpartum fever, cesarean delivery before 37 weeks during the previous cesarean
      (professional agreement). TOLAC can be considered if obstetrical conditions are
      favorable even if the delay is less than 6 months between the previous cesarean
      delivery and the date of conception of the following pregnancy (professional
      agreement). TOLAC can be considered after a previous myomectomy, depending on
      technical conditions under which the intervention was conducted (gradeC). TOLAC
      is possible even after previous hysteroscopic metroplasty for uterine septa or in
      cases of uterine perforation with monopolar coagulation (professional agreement).
      The type of uterine suture during the previous cesarean should not influence the
      choice of the route of delivery (professional agreement). TOLAC can be considered
      in cases of two previous cesarean sections if obstetrical conditions are
      favorable (professional agreement). Planned cesarean section is recommended from
      history of three previous cesarean sections (professional agreement). A planned
      cesarean section is recommended in cases of previous corporeal incision during
      cesarean (gradeC). There is not enough data to recommend ultrasonographic
      measurement of the lower uterine segment during pregnancy to help to determine
      the route of delivery (professional agreement). CONCLUSIONS: TOLAC can be
      considered, depending on obstetric conditions, in all situations studied, except
      in cases of previous obstetric corporeal incision or previous history of at least
      three cesareans.

PMID- 23142360
TI  - Age- and gender-related differences in cortical geometry and microstructure:
      Improved sensitivity by regional analysis.
AB  - OBJECTIVE: While the importance of cortical structure quantification is
      increasingly underscored by recent literature, conventional analysis techniques
      obscure potentially important regional variations in cortical structure. The
      objective of this study was to characterize the spatial variability in cortical
      geometry and microstructure at the distal radius and tibia using high resolution
      peripheral quantitative computed tomography (HR-pQCT). We show that spatially
      resolved analysis is able to identify cortical sub-regions with increased
      sensitivity to the effects of gender and aging. METHODS: HR-pQCT scans of 146
      volunteers (92 female/54 male) spanning a wide range of ages (20-78years) were
      analyzed. For each subject, radius and tibia scans were obtained using a clinical
      HR-pQCT system. Measures describing geometry (cortical bone thickness (Ct.Th)),
      microstructure (porosity (Ct.Po), pore diameter (Ct.Po.Dm), and pore size
      heterogeneity (Ct.Po.Dm SD)), and cortical bone density were calculated from the
      image data. Biomechanical parameters describing load and stress distribution were
      calculated using linear finite element analysis. Cortical quadrants were defined
      based on anatomic axes to quantify regional parameter variation. Subjects were
      categorized by gender, and age, and menopausal status for analysis. RESULTS:
      Significant regional variation was found in all geometric and microstructural
      parameters in both the radius and tibia. In general, the radius showed more
      pronounced and significant variations in all parameters as compared with the
      tibia. At both sites, Ct.Po displayed the greatest regional variations.
      Correlation coefficients for Ct.Po and Ct.Th with respect to load and stress
      distribution provided evidence of an association between regional cortical
      structure and biomechanics in the tibia. Comparing women to men, differences in
      Ct.Po were most pronounced in the anterior quadrant of the radius (36% lower in
      women (p<0.01)) and the posterior quadrant of the tibia (27% lower in women
      (p<0.01)). Comparing elderly to young women, differences in Ct.Po were most
      pronounced in the lateral quadrant of the radius (328% higher in elderly women
      (p<0.001)) and the anterior quadrant of the tibia (433% higher in elderly women
      (p<0.001)). Comparing elderly to young men, the most pronounced age differences
      were found in the anterior radius (205% higher in elderly men, (p<0.001)) and the
      anterior tibia (190% higher in elderly men (p<0.01)). All subregional Ct.Po
      differences provided greater sensitivity to gender and age effects than those
      based on the global means. CONCLUSION: These results show significant regional
      variation in all geometric and microarchitectural parameters studied in both the
      radius and tibia. Quantification of region-specific parameters provided increased
      sensitivity in the analysis of age- and gender-related differences, in many cases
      providing statistically significant differentiation of groups where conventional
      global analysis failed to detect differences. These results suggest that regional
      analysis may be important in studies of disease and therapeutic effects,
      particularly where microstructural parameters based on global analyses have thus
      far failed to identify a response in bone quality.

PMID- 23142361
TI  - Contributions of severe burn and disuse to bone structure and strength in rats.
AB  - Burn and disuse results in metabolic and bone changes associated with substantial
      and sustained bone loss. Such loss can lead to an increased fracture incidence
      and osteopenia. We studied the independent effects of burn and disuse on bone
      morphology, composition and strength, and microstructure of the bone alterations
      14days after injury. Sprague-Dawley rats were randomized into four groups:
      Sham/Ambulatory (SA), Burn/Ambulatory (BA), Sham/Hindlimb Unloaded (SH) and
      Burn/Hindlimb Unloaded (BH). Burn groups received a 40% total body surface area
      full-thickness scald burn. Disuse by hindlimb unloading was initiated immediately
      following injury. Bone turnover was determined in plasma and urine. Femur
      biomechanical parameters were measured by three-point bending tests and bone
      microarchitecture was determined by micro-computed tomography (uCT). On day 14, a
      significant reduction in body mass was observed as a result of burn, disuse and a
      combination of both. In terms of bone health, disuse alone and in combination
      affected femur weight, length and bone mineral content. Bending failure energy,
      an index of femur strength, was significantly reduced in all groups and maximum
      bending stress was lower when burn and disuse were combined. Osteocalcin was
      reduced in BA compared to the other groups, indicating influence of burn. The
      reductions observed in femur weight, BMC, biomechanical parameters and indices of
      bone formation are primarily responses to the combination of burn and disuse.
      These results offer insight into bone degradation following severe injury and
      disuse.

PMID- 23142362
TI  - Occurrence of new bone-like tissue formation in uremic tumoral calcinosis.
AB  - A 55-year-old woman who had been on hemodialysis for 5years was admitted for
      evaluation of a hard mass in the right hip region. Her serum calcium (Ca)
      phosphate (P) product was elevated. Radiographs showed periarticular calcified
      masses in the soft tissues around both hips and shoulders, which were
      characteristic of uremic tumoral calcinosis (UTC). Biopsy specimens were obtained
      from both right hip mass and the right iliac crest. Histological examination of
      hip mass revealed bone-like tissue with marrow, as well as calcified material.
      The bone-like tissue was categorized as heterotopic ossification (HO), because it
      had been formed inside soft tissue where bone-like tissue does not normally
      exist. Histological analysis of HO showed the formation of cancellous bone-like
      tissue. Woven mineralized bone-like tissue was predominant over lamellar bone
      like tissue. High bone turnover combined with osteitis fibrosa-like lesion was
      diagnosed because of an increase of the fibrous volume, as well as clear double
      tetracycline labeling. Near a site of HO, numerous ALP- and Runx2-positive
      cuboidal osteoblast-like cells and TRAP- and cathepsin K-positive multinucleated
      osteoclast-like cells were noted. Histomorphometric analysis of the right iliac
      crest revealed osteitis fibrosa. This is the first report of HO in a patient with
      UTC. After parathyroidectomy, the patient's Ca-P imbalance was corrected and UTC
      subsided. Although the mechanism by which new bone-like tissue formation arises
      in the soft tissues has not yet been determined, secondary hyperparathyroidism
      may have contributed to the progression of UTC in this patient.

PMID- 23142363
TI  - miR-326 associates with biochemical markers of bone turnover in lung cancer bone
      metastasis.
AB  - Recent evidence suggests that miRNAs could be used as serum markers in a variety
      of normal and pathological conditions. In this study, we aimed to identify novel
      miRNAs associated with skeletal metastatic disease in a preclinical model of lung
      cancer bone metastasis. We assessed the validity of these miRNAs as reliable
      serum biochemical markers to monitor the extent of disease and response to
      treatment in comparison to imaging techniques and standard biochemical markers of
      bone turnover. Using a murine model of human lung cancer bone metastasis after
      zoledronic acid (ZA) treatment, PINP (procollagen I amino-terminal propeptide)
      was the only marker that exhibited a strong correlation with osteolytic lesions
      and tumor burden at early and late stages of bone colonization. In contrast, BGP
      (osteocalcin) and CTX (carboxyterminal telopeptide) demonstrated a strong
      correlation only at late stages. We performed qPCR based screening of a panel of
      380 human miRNAs and quantified bone metastatic burden using micro-CT scans, X
      rays and bioluminescence imaging. Interestingly, levels of miR-326 strongly
      associated with tumor burden and PINP in vehicle-treated animals, whereas no
      association was found in ZA-treated animals. Only miR-193 was associated with
      biochemical markers PINP, BGP and CTX in ZA-treated animals. Consistently, miR
      326 and PINP demonstrated a strong correlation with tumor burden. Our findings,
      taken together, indicate that miR-326 could potentially serve as a novel
      biochemical marker for monitoring bone metastatic progression.

PMID- 23142364
TI  - Regulation of fatty acid synthase (FAS) and apoptosis in estrogen-receptor
      positive and negative breast cancer cells by conjugated linoleic acids.
AB  - BACKGROUND: Conjugated linoleic acids (CLAs) are natural dairy food components
      that exhibit a unique body of potential health benefits in animals and man,
      including anti-cardiovascular disease and anti-cancer effects. Several studies
      have demonstrated that fatty acid synthase (FAS) levels (protein and mRNA) are
      over expressed in many carcinomas. Sterol regulatory element binding proteins
      (SREBPs) are transcription factors that regulate genes involved in lipid
      metabolism, including FAS. METHODS: Breast cancer cell lines, MCF-7 and MDA-MB
      231 were treated with CLAs to investigate the regulation of SREBP-1c and FAS
      expression. RESULTS: In MDA-MB-231 cells, SREBP-1c and FAS were co-ordinately
      decreased by treatment with 25 MUM CLA 9-11 and 10-12. In MCF-7 cells, the
      decrease in SREBP-1c and FAS expression was dependant on the concentration of CLA
      used. CONCLUSIONS: The data suggest a differential effect of CLAs on SREBP-1c and
      FAS in estrogen receptor-positive (MCF-7) compared to estrogen receptor-negative
      (MDA-MB-231) breast cancer cells.

PMID- 23142365
TI  - "Ventilatory alternans": a left-right alternation of inspiratory airflow in
      humans.
AB  - In a study visualizing ventilation with hyperpolarized (3)He magnetic resonance
      imaging (MRI) in elite breath hold divers, the dynamic MRI images in one subject
      exhibited an apparent alternation of the image intensity between left and right
      lung. We hypothesized that the alternation resulted from alternating variations
      in inspiratory flow rate to left and right lungs. Analysis showed that the
      alternation was not due to random uncorrelated temporal fluctuations of intensity
      (p<0.001). The frequency of alternation was approximately 56 min(-1), suggesting
      a cardiac origin. Similar alternation of ventilation was confirmed
      retrospectively in 4 of 6 additional subjects. These observations are consistent
      with previous studies showing cardiogenic mixing of gas in the lung. We speculate
      that cardiogenic pendelluft, possibly from ballistic lateral motion of the
      beating heart, could cause alternating variations of inspiratory flow to the
      lungs.

PMID- 23142366
TI  - Chronic administration of AFQ056/Mavoglurant restores social behaviour in Fmr1
      knockout mice.
AB  - Fragile X syndrome is caused by lack of FMR1 protein (FMRP) leading to severe
      symptoms, including intellectual disability, hyperactivity and autistic-like
      behaviour. FMRP is an RNA binding protein involved in the regulation of
      translation of specific target mRNAs upon stimulation of metabotropic glutamate
      receptor 5 (mGluR5) at the synapse. The absence of FMRP leads to enhanced
      activity of mGluR5 signal transduction pathways. Many conflicting results have
      been reported regarding social behaviour deficits in Fmr1 knockout mice, and
      little is known about the involvement of mGluR5 pathways on social behaviour. In
      this study, a three-chambered task was used to determine sociability and
      preference for social novelty in Fmr1 knockout mice. Disruption of Fmr1
      functioning resulted in enhanced interaction with stranger mouse during
      sociability while no significant changes were observed during preference for
      social novelty assay. Chronic administration of a specific mGluR5 antagonist,
      AFQ056/Mavoglurant, was able to restore sociability behaviour of Fmr1 knockout
      mice to levels of wild type littermates. These results support the importance of
      mGluR5 signalling pathways on social interaction behaviour and that
      AFQ056/Mavoglurant might be useful as potential therapeutic intervention to
      rescue various behavioural aspects of the fragile X phenotype.

PMID- 23142367
TI  - Altered anxiety and defensive behaviors in Bax knockout mice.
AB  - Developmental neuronal cell death is critically regulated by the pro-death
      protein Bax. Bax-/- mice exhibit increased neuron number, the elimination of
      several neural sex differences, and altered socio-sexual behaviors. Here we
      examined the effects of Bax gene deletion on anxiety and defensive behaviors by
      comparing the responses of male and female wildtype and Bax-/- mice to two
      different tests. On the elevated plus maze, Bax-/- mice of both sexes made more
      entries into and spent more time in the outer portion of open arms, indicating
      decreased anxiety compared to wildtype animals. Next, we exposed mice to two
      odors: trimethylthiazoline (TMT), an olfactory component of fox feces that
      rodents find aversive, and butyric acid (BA), an aversive odor without ecological
      significance. Each odor was presented individually and all animals were tested
      with both odors in a counterbalanced design. TMT was consistently more aversive
      than BA across a variety of behaviors (e.g., mice spent less time close to the
      odor source). Overall, Bax -/- mice showed fewer stretch approaches to both TMT
      and BA than wildtypes, but they avoided the odor source more (e.g., fewer
      contacts and less time spent in proximity). Finally, no effect of genotype was
      seen in baseline olfactory behavior; all mice were able to locate a buried food
      item, demonstrating that Bax-/- mice do not have impaired olfaction per se.
      Collectively, these data suggest a change in strategy with anxiety and defensive
      behaviors in Bax-/- mice, indicating that alterations in cell number affect more
      general mechanisms of fear and anxiety in addition to behaviors directly related
      to reproduction.

PMID- 23142368
TI  - Generalization of adaptation to a complex visuo-motor transformation across the
      workspace.
AB  - For the efficient use of tools, the visuo-motor transformation relating body
      movements to movements of the effective part of the tool has to be learned. Here
      we ask whether adaptation to a complex tool transformation generalizes to new
      regions of the workspace of the tool. Three groups of participants performed goal
      directed movements of a cursor on a computer monitor. The cursor represented the
      tip of the load arm of a sliding lever, while the hand of the participants moved
      the tip of the effort arm of the same lever. Each group learned a particular
      relation between movements of the effort arm and of the load arm as it was
      associated with a certain region of the workspace. In the transfer test, targets
      in three different regions of the workspace were presented, only one of them each
      group had encountered during practice. Adaptation to the visuo-motor
      transformation turned out to generalize across the workspace of the tool.
      However, the generalization exhibited different patterns for the three groups
      which reflected the respective regions of the workspace where the transformation
      had been learned. We conclude that the acquired internal representation of the
      visuo-motor transformation is local and does not allow extrapolation to new
      regions of the workspace. It likely consists of a symmetry approximation, which
      is valid across the whole workspace of the tool and largely accessible to
      conscious awareness, and a rather implicit local fine tuning, which is specific
      to local regions of the workspace.

PMID- 23142369
TI  - Prefrontal cortex activity, sympatho-vagal reaction and behaviour distinguish
      between situations of feed reward and frustration in dwarf goats.
AB  - Recent concepts relating to animal welfare accept that animals experience
      affective states. These are notoriously difficult to measure in non-verbal
      species, but it is generally agreed that emotional reactions consist of well
      coordinated reactions in behaviour, autonomic and brain activation. The aim of
      the study was to evaluate whether each or a combination of these aspects can
      differentiate between situations presumed to differ in emotional content. To this
      end, we repeatedly confronted dwarf goats at short intervals with a covered and
      an uncovered feed bowl (i.e. presumably frustrating and rewarding situations
      respectively) whilst simultaneously observing their behaviour, measuring heart
      rate and heart-rate variability and haemodynamic changes in the prefrontal cortex
      using functional near-infrared spectroscopy. When faced with a covered feed bowl,
      goats occupied themselves at locations away from the bowl and showed increased
      locomotion, while there was a general increase in prefrontal cortical activity.
      There was little indication of autonomic changes. In contrast, when feed was
      accessible, the goats reduced locomotion, focused their behaviour on the feed
      bowl, showed signs of sympathetically mediated arousal reflecting anticipation
      and, if any cortical activity at all was present, it was concentrated to the left
      hemisphere. We thus observed patterns in behaviour, sympathetic reaction and
      brain activity that distinguished between a situation of frustration and one of
      reward in dwarf goats. These patterns consisted of a well-coordinated set of
      reactions appropriate in respect of the emotional content of the stimuli used.

PMID- 23142370
TI  - Lycopodine triggers apoptosis by modulating 5-lipoxygenase, and depolarizing
      mitochondrial membrane potential in androgen sensitive and refractory prostate
      cancer cells without modulating p53 activity: signaling cascade and drug-DNA
      interaction.
AB  - When the prostate cancer cells become unresponsive to androgen therapy,
      resistance to chemotherapy becomes imminent, resulting in high mortality. To
      combat this situation, lycopodine, a pharmacologically important bioactive
      component derived from Lycopodium clavatum spores, was tested against hormone
      sensitive (LnCaP) and refractory (PC3) prostate cancer cells in vitro. This study
      aims to check if lycopodine has demonstrable anti-cancer effects and if it has,
      to find out the possible mechanism of its action. The MTT assay was performed to
      evaluate the cytotoxic effect. Depolarization of mitochondrial membrane
      potential, cell cycle, EGF receptor activity and apoptosis were recorded by FACS;
      profiles of different anti- and pro-apoptotic genes and their products were
      studied by semi-quantitative RT-PCR, indirect-ELISA, western blotting. Drug-DNA
      interaction was determined by CD spectroscopy. Administration of lycopodine down
      regulated the expression of 5-lipoxygenase and the 5-oxo-ETE receptor (OXE
      receptor1) and EGF receptor, and caused up-regulation of cytochrome c with
      depolarization of mitochondrial inner membrane potential, without palpable change
      in p53 activity, resulting in apoptosis, cell arrest at G0/G1 stage and
      ultimately reduced proliferation of cancer cells; concomitantly, there was
      externalization of phosphotidyl serine residues. CD spectroscopic analysis
      revealed intercalating property of lycopodine with DNA molecule, implicating its
      ability to block cellular DNA synthesis. The overall results suggest that
      lycopodine is a promising candidate suitable for therapeutic use as an anti
      cancer drug.

PMID- 23142371
TI  - CNR1 gene deletion affects the density of endomorphin-2 binding sites in the
      mouse brain in a hemisphere-specific manner.
AB  - Endomorphin-1 (EM-1) and endomorphin-2 (EM-2) are two endogenous tetrapeptides
      with very high affinities for the MU-opioid receptor. Until recently, the precise
      neuroanatomical localization of the binding sites for these peptides was unknown.
      However, the recent synthesis of tritiated forms of these molecules has permitted
      these binding sites to be analysed with a very high degree of neuroanatomical
      specificity. Preliminary studies demonstrated a superior binding profile for EM
      2, with less non-specific binding than EM-1. As the endogenous cannabinoid and
      opioid systems interact at several levels, we investigated how deletion of the
      CNR1 gene, which encodes the cannabinoid receptor 1 (CB(1)R) protein, affects the
      brain distribution of EM-2 binding sites. Our results revealed no differences in
      the average density of EM-2 binding sites in CB(1) receptor knockout (CB(1)R KO)
      and WT mice. However, when both hemispheres were analysed separately, we detected
      specific alterations in the distribution of EM-2 binding sites in the right
      hemisphere of CB(1)R KO mice. While, the density of EM-2 binding sites in CB(1)R
      KO mice was higher in the CA3 hippocampal field and in the pontine tegmental
      nuclei, it was lower in the superior colliculus and ventral tegmental area than
      in WT controls. No differences were observed in the left hemisphere for any of
      the regions analysed. For the first time these findings demonstrate a
      lateralization effect on cerebral opioid binding sites that may be mediated by
      the central cannabinoid system.

PMID- 23142372
TI  - In vivo characterization of intestinal effects of endomorphin-1 and endomorphin-2
      in type 1 diabetic mice.
AB  - Previously, we have demonstrated that type 1 diabetes significantly attenuated
      the effects of endomorphins on mouse colonic contractions in vitro. In the
      present study, to further assess whether diabetes affects the in vivo effects of
      endomorphins on the mouse intestinal motility, we investigated the effects of
      endomorphins on colonic propulsion and large intestinal transit in diabetic mice.
      Both colonic bead expulsion and large intestinal transit were significantly
      delayed in 4 and 8 weeks diabetic mice compared to non-diabetic mice. Moreover,
      intracerebroventricular (i.c.v.) administration of EM-1 and EM-2 (0.5, 1.5 and 5
      nmol/mouse) significantly increased bead expulsion latency in a dose-dependent
      manner both in non-diabetic and diabetic mice. Similar results were found in
      large intestinal transit. However, the inhibitory effects of colonic propulsion
      induced by endomorphins were significantly attenuated in diabetes compared to non
      diabetes. It is noteworthy that the inhibition of distal colonic propulsion
      induced by EM-1 in 8-week diabetes was lower than that of in 4 weeks diabetes.
      Nevertheless, there was no significant influence on endomorphins-induced
      inhibition of large intestinal transit caused by diabetes. Co-administration of
      naloxone (10 nmol/mouse, i.c.v.) significantly attenuated the inhibitory effects
      of endomorphins (5 nmol/mouse, i.c.v.) on colonic bead expulsion and large
      intestinal transit in 4 weeks diabetes, indicating that opioid receptor involved
      in these effects. Our results indicated that type 1 diabetes attenuated the
      inhibition of distal colonic propulsion induced by endomorphins in mice, but not
      the large intestine. The central opioid mechanism was involved in the
      endomorphins-induced intestinal effects in diabetes.

PMID- 23142373
TI  - Spinal serotonin 5-HT7 and adenosine A1 receptors, as well as peripheral
      adenosine A1 receptors, are involved in antinociception by systemically
      administered amitriptyline.
AB  - The present study explored a link between spinal 5-HT(7) and adenosine A(1)
      receptors in antinociception by systemic amitriptyline in normal and adenosine
      A(1) receptor knock-out mice using the 2% formalin test. In normal mice,
      antinociception by systemic amitriptyline 3mg/kg was blocked by intrathecal
      administration of the selective adenosine A(1) receptor antagonist 8-cyclopentyl
      1,3-dipropylxanthine (DPCPX) 10 nmol. Blockade was also seen in adenosine A(1)
      receptor +/+ mice, but not in -/- mice lacking these receptors. In both normal
      and adenosine A(1) receptor +/+ mice, the selective 5-HT(7) receptor antagonist
      (2R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrrolidine
      hydrochloride (SB269970) 3 MUg blocked antinociception by systemic amitriptyline,
      but it did not prevent antinociception in adenosine A(1) receptor -/- mice. In
      normal mice, flinching was unaltered when the selective 5-HT(7) receptor agonist
      (2S)-(+)-5-(1,3,5-trimethylpyrazol-4-yl)-2-(dimethylamino)tetralin (AS-19) 20 MUg
      was administered alone, but increased when co-administered intrathecally with
      DPCPX 10 nmol or SB269970 3 MUg. Intrathecal AS-19 decreased flinching in
      adenosine A(1) receptor +/+ mice compared to -/- mice. Systemic amitriptyline
      appears to reduce nociception by activating spinal adenosine A(1) receptors
      secondarily to 5-HT(7) receptors. Spinal actions constitute only one aspect of
      antinociception by amitriptyline, as intraplantar DPCPX 10 nmol blocked
      antinociception by systemic amitriptyline in normal and adenosine A(1) receptor
      +/+, but not -/- mice. Adenosine A(1) receptor interactions are worthy of
      attention, as chronic oral caffeine (0.1, 0.3g/L, doses considered relevant to
      human intake levels) blocked antinociception by systemic amitriptyline in normal
      mice. In conclusion, adenosine A(1) receptors contribute to antinociception by
      systemic amitriptyline in both spinal and peripheral compartments.

PMID- 23142374
TI  - High-density oligonucleotide-based resequencing assay for mutations causing
      syndromic and non-syndromic forms of thoracic aortic aneurysms and dissections.
AB  - Thoracic aortic aneurysm and dissection is associated with increasing mortality
      rate that may occur as part of a syndrome or as an isolated familial condition.
      Several genes have been implicated in causing TAAD, though an appropriate genetic
      test for their parallel testing is not yet available. Herein, we describe the
      novel 117-kb "MFSTAAD chip" that may help to understand the genetic basis of
      TAAD. A custom duplicate resequencing assay was developed to cover eight genes
      previously described in TAAD; FBN1, TGFBR1&2, COL3A1, MYH11, ACTA2, SLC2A10 and
      NOTCH1. GSEQ and SeqC software were used for data analysis. The analytical
      sensitivity of the assay was validated by the recognition of 182 known mutations
      (153 point mutations, 21 deletions, 7 insertions and 1 duplication) and a cohort
      of 28 patients were selected to determine the mutation yield, whereby 18 of them
      were previously negative for mutations in the genes FBN1 and TGFBR2. The assay
      had significantly higher sensitivity for point mutations (100%) and the largest
      deletion of 16 bp was detectable through a decline in the hybridization strength.
      The overall analytical sensitivity was 85%. Mutation testing of 28 unrelated TAAD
      patients revealed 4 known and 6 possibly pathogenic mutations with a mutation
      yield of 32%. The MFSTAAD chip is an alternative tool to next-generation
      sequencing that allows parallel analysis of several genes on a single platform.
      Refinements in the probe design and data analysis software will increase the
      analytical sensitivity of insertions and deletions making this assay even more
      applicable for clinical testing.

PMID- 23142375
TI  - Molecular confirmation of founder mutation c.-167A>G in Tunisian patients with
      PMLD disease.
AB  - Pelizaeus Merzbacher disease and Pelizaeus Merzbacher like disease (PMLD) are
      hypomyelinating leucodystrophies of the central nervous system (CNS) with a very
      similar phenotype. PMD is an X-linked recessive condition caused by mutations,
      deletion duplication or triplication of the proteolipid protein 1 gene (PLP1).
      However, PMLD is a recessive autosomal hypomyelinating leukodystrophy caused by
      mutations of the GJC2 gene. In this study, we analyzed 5 patients belonging to 4
      Tunisian families. Direct sequencing of GJC2 gene in all probands showed the same
      homozygous founder mutation c.-167A>G localized in the promoter region. We also
      generated two microsatellite markers GJC2 195GT and GJC2 76AC closed to the GJC2
      gene to confirm the presence of a founder effect for this mutation. Haplotype
      study showed that the c.-167A>G promoter mutation occurred in a specific founder
      haplotype in Tunisian population. The identification of this founder mutation has
      important implications towards genetic counseling in relatives of these families
      and the antenatal diagnosis.

PMID- 23142376
TI  - 8q12.1q12.3 de novo microdeletion involving the CHD7 gene in a patient without
      the major features of CHARGE syndrome: case report and critical review of the
      literature.
AB  - CHARGE syndrome is an autosomal dominant inherited disorder characterized by a
      specific and recognizable pattern of anomalies. De novo mutations or deletions of
      the gene encoding chromodomain helicase DNA binding protein 7 (CHD7) are the
      major cause of CHARGE syndrome. In this report, we describe a patient with a
      typical phenotype characterized by psychomotor retardation, hypertrichosis,
      facial asymmetry, synophria, failure to thrive, developmental delay and gastro
      esophageal reflux, carrying a de novo 6.04Mb interstitial deletion in 8q12.1q12.3
      detected by single nucleotide polymorphism (SNP) array analysis. Despite the
      deletion includes CHD7 and although the patient shares some of the clinical
      features of the CHARGE syndrome, she does not fulfill the clinical criteria for
      this syndrome. To the best of our knowledge, this is the second case with an
      entire deletion of the CHD7 gene not leading to CHARGE syndrome and, for this
      reason, useful to expand and further delineate the clinical features associated
      with the 8q12.1q12.3 deletion. Furthermore, the literature review revealed that
      the phenotype secondary to duplications of the same region partially overlaps
      with the phenotype reported in this study. Selected genes that are present in the
      hemizygous state and which might be important for the phenotype of this patient,
      are discussed in context of the clinical features.

PMID- 23142377
TI  - Association study of IL28B: rs12979860 and rs8099917 polymorphisms with SVR in
      patients infected with chronic HCV genotype 1 to PEG-INF/RBV therapy using
      systematic meta-analysis.
AB  - Recently, genome-wide associated studies (GWAS) have identified that host
      genetics IL28B SNPs rs12979860 and rs8099917 were significantly associated with
      SVR in patients infected with chronic HCV genotype 1 to PEG-INF/RBV therapy.
      Results from these studies remain conflicting. We conducted this meta-analysis to
      estimate the overall association of SVR with rs12979860 and rs8099917. We
      searched the PubMed, Embase, Scholar Google, ISI Web of Knowledge, and Chinese
      National Knowledge Infrastructure (CNKI) databases for all articles before July
      30, 2012. The odds ratio (OR) corresponding to the 95% confidence interval (CI)
      was used to assess the association. The statistical heterogeneity among studies
      was assessed with the I(2) statistics. Begg's test and Egger's test were
      performed to evaluate the publication bias. Eventually, twenty studies were
      selected for the meta-analysis. The IL-28B SNPs rs12979860 genotype CC and
      rs8099917 genotype TT significantly positive associated with SVR in patients
      infected chronic HCV genotype 1 to PEG-INF/RBV therapy (OR=4.473, 95% CI=3.814
      5.246, OR=5.171, 95% CI=4.372-6.117 respectively). The results suggested that
      rs12979860 genotype CC and rs8099917 genotype TT could be used as independent
      predictors of the HCV-1 infected patients.

PMID- 23142378
TI  - Investigation of CYP21A2 mutations in Turkish patients with 21-hydroxylase
      deficiency and a novel founder mutation.
AB  - Congenital adrenal hyperplasia (CAH) is a group of autosomal recessively
      inherited disorders characterized by impaired production of adrenal steroids.
      Approximately 95% of all CAH are caused by mutations of the CYP21A2 that encodes
      21-hydroxylase. In this study, mutation analyses of CYP21A2 were performed in 48
      CAH patients from 45 Turkish families with the clinical diagnosis of 21
      hydroxylase deficiency (21OHD). While in 39 (86.7%) of 21OHD patients, disease
      causing CYP21A2 mutations were identified in both alleles, in two 21OHD patients
      CYP21A2 mutations were identified only in one allele. In four patients, mutation
      was not detected at all. In total, seventeen known and one novel, disease causing
      CYP21A2 mutations were observed. Among identified mutations, previously described
      c.293-13C/A>G, large rearrangements and p.Q319X mutations were the most common
      mutations accounting for 33.3%, 14.4% and 12.2% of all evaluated chromosomes,
      respectively. In six families (13.3%) a novel founder mutation, c.2T>C (p.M1?),
      inactivating the translation initiation codon was found. This mutation is not
      present in pseudogene CYP21A1P and causes the classical form of the disease in
      six patients. In addition, depending on the nature of the rearrangements
      CYP21A1P/CYP21A2 chimeras were further classified as CH(c/d), and CH-1(c) was
      shown to be the most prominent chimera in our study group. In conclusion, with
      this study we identified a novel founder CYP21A2 mutation and suggest a further
      classification for CYP21A1P/CYP21A2 chimeras depending on the combination of
      junction site position and whether it is occurred as a result of deletion or
      conversion. Absence of disease causing mutation of CYP21A2 in ten of screened
      ninety chromosomes suggests the contribution of regulatory elements in
      occurrences of CAH due to the 21OHD.

PMID- 23142379
TI  - Galectin-1 controls cardiac inflammation and ventricular remodeling during acute
      myocardial infarction.
AB  - Galectin-1 (Gal-1), an evolutionarily conserved beta-galactoside-binding lectin,
      plays essential roles in the control of inflammation and neovascularization.
      Although identified as a major component of the contractile apparatus of
      cardiomyocytes, the potential role of Gal-1 in modulating heart pathophysiology
      is uncertain. Here, we aimed to characterize Gal-1 expression and function in the
      infarcted heart. Expression of Gal-1 was substantially increased in the mouse
      heart 7 days after acute myocardial infarction (AMI) and in hearts from patients
      with end-stage chronic heart failure. This lectin was localized mainly in
      cardiomyocytes and inflammatory infiltrates in peri-infarct areas, but not in
      remote areas. Both simulated hypoxia and proinflammatory cytokines selectively up
      regulated Gal-1 expression in mouse cardiomyocytes, whereas anti-inflammatory
      cytokines inhibited expression of this lectin or had no considerable effect.
      Compared with their wild-type counterpart, Gal-1-deficient (Lgals1(-/-)) mice
      showed enhanced cardiac inflammation, characterized by increased numbers of
      macrophages, natural killer cells, and total T cells, but reduced frequency of
      regulatory T cells, leading to impaired cardiac function at baseline and impaired
      ventricular remodeling 7 days after nonreperfused AMI. Treatment of mice with
      recombinant Gal-1 attenuated cardiac damage in reperfused AMI. Taken together,
      our results indicate a protective role for Gal-1 in normal cardiac homeostasis
      and postinfarction remodeling by preventing cardiac inflammation. Thus, Gal-1
      treatment represents a potential novel strategy to attenuate heart failure in
      AMI.

PMID- 23142380
TI  - Transforming growth factor beta-1 stimulates profibrotic epithelial signaling to
      activate pericyte-myofibroblast transition in obstructive kidney fibrosis.
AB  - Pericytes have been identified as the major source of precursors of scar
      producing myofibroblasts during kidney fibrosis. The underlying mechanisms
      triggering pericyte-myofibroblast transition are poorly understood. Transforming
      growth factor beta-1 (TGF-beta1) is well recognized as a pluripotent cytokine
      that drives organ fibrosis. We investigated the role of TGF-beta1 in inducing
      profibrotic signaling from epithelial cells to activate pericyte-myofibroblast
      transition. Increased expression of TGF-beta1 was detected predominantly in
      injured epithelium after unilateral ureteral obstruction, whereas downstream
      signaling from the TGF-beta1 receptor increased in both injured epithelium and
      pericytes. In mice with ureteral obstruction that were treated with the pan anti
      TGF-beta antibody (1D11) or TGF-beta receptor type I inhibitor (SB431542), kidney
      pericyte-myofibroblast transition was blunted. The consequence was marked
      attenuation of fibrosis. In addition, epithelial cell cycle G2/M arrest and
      production of profibrotic cytokines were both attenuated. Although TGF-beta1
      alone did not trigger pericyte proliferation in vitro, it robustly induced alpha
      smooth muscle actin (alpha-SMA). In cultured kidney epithelial cells, TGF-beta1
      stimulated G2/M arrest and production of profibrotic cytokines that had the
      capacity to stimulate proliferation and transition of pericytes to
      myofibroblasts. In conclusion, this study identified a novel link between injured
      epithelium and pericyte-myofibroblast transition through TGF-beta1 during kidney
      fibrosis.

PMID- 23142381
TI  - HACE1 is a tumor suppressor gene candidate in natural killer cell neoplasms.
AB  - HACE1 is an E3 ubiquitin ligase located in 6q21, the genomic region frequently
      deleted in natural killer (NK) cell malignancies. Here, we report HACE1 as a
      candidate tumor suppressor gene silenced through a combination of deletion and
      cytosine phosphate guanine island hypermethylation. We detected deletion of HACE1
      in malignant NK cell lines (6 of 9, 67%) and primary biopsies (5 of 15, 33%) by
      quantitative PCR, with most of the specimen showing cytosine phosphate guanine
      island hypermethylation in the remaining allele, leading to low mRNA
      transcription. The ectopic expression of HACE1 in an HACE1-null NK cell line led
      to apoptosis and G2/M cell cycle arrest. Moreover, HACE1 expression was up
      regulated in IL-2-activated normal NK cells and NK cells cocultured with an
      engineered NK cell target, K562 Clone 9.mbIL21, suggesting its role in the
      regulation of NK cell homeostasis. In conclusion, HACE1 is another potent tumor
      suppressor gene located within the 6q21 region, and loss of function of multiple
      tumor suppressor genes within 6q21 may be a critical determinant of NK cell
      lymphomagenesis.

PMID- 23142382
TI  - Transcription factor-7-like 2 gene variants are strongly associated with type 2
      diabetes in Tunisian Arab subjects.
AB  - Genome-wide association studies validated transcription factor 7-like 2 (TCF7L2)
      gene as confirmed type 2 diabetes (T2DM) susceptibility locus, and an ethnic
      contribution of TCF7L2 variants to T2DM risk was indicated. The aim of this study
      was to replicate in a Tunisian Arab population identified associations of common
      TCF7L2 variants with T2DM. We tested the association of TCF7L2 variants:
      rs4506565, rs7903146, rs12243326, and rs12255372, with T2DM in 900 Tunisian
      patients and 875 control subjects. TCF7L2 genotyping was done by allelic
      discrimination/real-time PCR method. Minor allele frequencies of rs4506565
      (P=2.4*10(-8)), rs7903146 (P=1.2*10(-6)), rs12243326 (P=8.4*10(-8)) and
      rs12255372 (P=1.1*10(-5)) were significantly higher in cases. The four tested
      TCF7L2 variants were in linkage disequilibrium, and 4-locus (rs4506565,
      rs7903146, rs12243326, rs12255372) haplotype analysis demonstrated that haplotype
      1111 was negatively associated (Pc<0.001), while haplotypes 2222 (Pc=0.008) and
      2211 (Pc=0.020) were positively associated with T2DM risk, after controlling for
      a number of covariates. The strong contribution of TCF7L2 gene variants to T2DM
      among Tunisians is in line with similar findings in other ethnic groups,
      confirming TCF7L2 as a common T2DM candidate gene.

PMID- 23142383
TI  - Association of the common FTO-rs9939609 polymorphism with type 2 diabetes,
      independent of obesity-related traits in a Vietnamese population.
AB  - Type 2 diabetes (T2D) is a complex disorder resulting from both genetic and
      environmental factors in its pathogenesis. A case-control study was designed with
      subjects recruited from a general population to investigate whether the
      association between T2D and the common T>A polymorphism (rs9939609) in fat mass
      and obesity associated (FTO) gene is mediated by obesity-related measurements,
      considering the contribution of socio-economic status and lifestyle factors. The
      significant association between the FTO rs9939609 polymorphism and T2D was first
      observed in the model unadjusted (OR per A allele=1.61, 95% CI=1.06-2.44,
      P=0.024). It remained consistently replicated in the final model after
      adjustments for sex, age, systolic blood pressure, socio-economic status,
      lifestyle factors, and obesity-related measurements (body mass index, waist-hip
      ratio, body fat percentage, and body adiposity index), showing an increased T2D
      risk with an additive effect of the alleles (ORs per A allele=1.80-1.92, 95%
      CI=1.09-3.19, P<0.05). The FTO-rs9939609 polymorphism, systolic blood pressure,
      and waist-hip ratio were the most significant independent predictors for T2D, in
      which the power of the adjusted prediction model was 0.769. In conclusion, the
      study suggested that the FTO-rs9939609 polymorphism was significantly associated
      with the increased risk of T2D, independent of obesity-related measurements in a
      Vietnamese population.

PMID- 23142384
TI  - Expression and promoter analysis of a highly restricted integrin alpha gene in
      vascular smooth muscle.
AB  - Full genome annotation requires gene expression analysis and elucidation of
      promoter activity. Here, we analyzed the expression and promoter of a highly
      restricted integrin gene, Itga8. RNase protection and quantitative RT-PCR showed
      Itga8 to be expressed most abundantly in vascular smooth muscle cells (SMC).
      Transcription start site mapping of Itga8 revealed the immediate 5' promoter
      region to be poorly conserved with orthologous sequences in the human genome.
      Further comparative sequence analysis showed a number of conserved non-coding
      sequence modules around the Itga8 gene. The immediate promoter region and an
      upstream conserved sequence module were each found to contain a CArG box, which
      is a binding site for serum response factor (SRF). Luciferase reporter assays
      revealed activity of several Itga8 promoter constructs with no apparent
      restricted activity to SMC types. Further, neither SRF nor its coactivator,
      Myocardin (MYOCD), was able to induce several distinct Itga8 promoter constructs.
      Transgenic mouse studies failed to reveal Itga8 promoter activity, indicating
      distal regulatory elements likely control this gene's in vivo expression profile.
      Interestingly, although the promoter was unresponsive to SRF/MYOCD, the
      endogenous Itga8 gene showed increases in expression upon ectopic MYOCD
      expression even though knockdown of SRF both in vitro and in vivo failed to
      demonstrate a corresponding change in Itga8. Collectively, these data demonstrate
      that Itga8 expression is CArG-SRF independent, but MYOCD dependent through an as
      yet unknown sequence module that is distal from the promoter region.

PMID- 23142385
TI  - Higher frequency of septic shock in septic patients with the 47C allele (rs4880)
      of the SOD2 gene.
AB  - AIM: To analyze the effect of the two different versions of the manganese
      superoxide dismutase gene (SOD2) on sepsis. The SOD2 gene presents the 47C>T
      single nucleotide polymorphism (SNP; ID: rs4880) which produces MnSOD with
      different activities. The -9Val MnSOD (47T allele) is less efficient than the 
      9Ala version (47C allele). During sepsis there are abundance of ROS, high SOD2
      expression and excess of H(2)O(2) synthesis. High concentrations of H(2)O(2)
      could affect the sepsis scenario and/or the sepsis outcome. METHODS: We
      determined the 47C>T single nucleotide polymorphism (SNP) frequencies in 529
      critically ill patients with or without sepsis, facing outcome. To collect
      information on population frequencies, we obtained a pilot 47C>T genotypic and
      allelic frequencies in a random group of 139 healthy subjects. RESULTS: We
      compared the 47C allele carriers (47CC+47CT genotypes) with 47TT homozygotes and
      noticed a significant association between 47C allele carriers and septic shock in
      septic patients (P=0.025). With an adjusted binary multivariate logistic
      regression, incorporating 47C>T SNP and the main clinical predictors, we showed
      high SOFA scores [P<0.001, OR=9.107 (95% CI=5.319-15.592)] and 47C allele
      [P=0.011, OR=2.125 (95% CI=1.190-3.794)] were significantly associated with
      septic shock outcome. With this information we presented a hypothesis suggesting
      that this negative outcome from sepsis is possibly explained by effects on
      cellular stress caused by 47C allele. CONCLUSION: In our population there was a
      significant higher frequency of septic shock in septic patients with the 47C
      allele of the SOD2 gene. This higher 47C allele frequency in septic patients with
      negative outcome could be explained by effects of higher activity MnSOD on
      cellular stress during the sepsis.

PMID- 23142386
TI  - Genomic organization, polymorphisms and molecular evolution of the goose-type
      lysozyme gene from Zhikong scallop Chlamys farreri.
AB  - Lysozyme is a ubiquitous hydrolase that plays an important role in protecting the
      host against pathogenic infection. In the present study, the genomic DNA sequence
      of an invertebrate goose type (G type) lysozyme (designated CfLysG) was cloned
      from Zhikong scallop Chlamys farreri by genome walking technique. The full-length
      DNA of CfLysG gene was of 9455bp, and the fragment from the transcription site to
      the polyadenylation site was of 8217bp. A total of 104 SNPs and 29 ins-del
      polymorphisms were identified in the genomic sequence of CfLysG, and most of them
      were located in the promoter and intron regions, except for three SNPs located in
      the exon regions. Some putative transcription factor binding sites in the
      promoter region suggested the involvement of CfLysG in immune responses. There
      were six exons of 55, 60, 90, 113, 145 and 140bp interrupted by five relatively
      large introns in the genomic DNA sequence. CfLysG exhibited a unique exon-intron
      organization which was different from both its vertebrate and invertebrate
      homologues. Though some introns were lost in the urochordate homologues, four of
      the five introns in CfLysG DNA shared homologous positions with vertebrate G type
      lysozyme genes, which indicated the existence of these introns in the ancestry of
      G type lysozyme. With respect to the number and size of both exons and introns,
      the gene organization of CfLysG was more similar to that of vertebrate G type
      lysozyme, but its amino acid sequence shared higher similarity with that of other
      invertebrate G type lysozymes. In the phylogenic tree, G type lysozymes from
      mollusk were clustered together and formed a sister clade to the urochordate and
      vertebrate G type lysozymes. G type lysozyme was separated from C and I type
      lysozymes and closely matched to the phage-type lysozyme. The results suggested
      that G type lysozyme might be evolutionarily closest to the lysozyme ancestor,
      and they would be helpful to understand the evolution of lysozyme genes.

PMID- 23142387
TI  - The mitochondrial genome of Aelurostrongylus abstrusus-diagnostic,
      epidemiological and systematic implications.
AB  - Aelurostrongylus abstrusus (Railliet, 1898) is a metastrongylid nematode of major
      clinical relevance in felids, causing aelurostrongylosis. In spite of its
      clinical importance in cats, the genetics, epidemiology and biology of this
      parasite are not entirely understood. mt DNA can provide markers for studies of
      these areas, but genetic data are scant for A. abstrusus and related lungworms.
      Here, the mt genome was amplified by long-range polymerase chain reaction (long
      PCR) from a single male adult of A. abstrusus, sequenced using 454 technology and
      annotated using an established bioinformatic pipeline. This circular mt genome is
      13,913 bp and contains two ribosomal RNA, 12 protein-coding and 22 transfer RNA
      genes, consistent with most other chromadorean nematodes. This genome should
      provide a source of markers for future investigations of the epidemiology and
      ecology of A. abstrusus. Molecular tools, employing such mt markers, are likely
      to find utility for explorations into the epidemiology, biology and systematics
      of this parasite, and the diagnosis of feline aelurostrongylosis.

PMID- 23142388
TI  - Haplotype distribution in the GLI3 gene and their associations with growth traits
      in cattle.
AB  - The glioma-associated oncogene family zinc finger 3 gene (GLI3) mediates in all
      vertebrates hedgehog (Hh) signaling that plays an essential role in the induction
      and patterning of numerous cell types during invertebrate and vertebrate
      development. In this study, a total of 6 single nucleotide polymorphisms (SNPs: 1
      6) were identified by polymerase chain reaction-single stranded conformational
      polymorphism (PCR-SSCP) and DNA pool sequencing, including all 13 exons and 12
      exon-intron boundaries within the bovine GLI3 gene. 16 haplotypes and 13 combined
      genotypes were revealed and the linkage disequilibrium was assessed in 708
      individuals representing three main cattle breeds from China. The statistical
      analyses indicated that the SNP2, 3 and 4 are associated with the body weight at
      birth and 6 months in Nanyang cattle population (P<0.05). No significant
      association was detected between 11 combined genotypes and body weight at five
      different ages. Our results provide evidence that polymorphisms in the GLI3 gene
      are associated with growth traits, and may be used for marker-assisted selection
      in beef cattle breeding program.

PMID- 23142389
TI  - My comments about the paper do not adequately describe the serious failures that
      have occurred in the peer review process at FCT.

PMID- 23142390
TI  - Comment on "Long term toxicity of a Roundup herbicide and a Roundup-tolerant
      genetically modified maize" by Seralini et al.

PMID- 23142391
TI  - Adverse effects in a feeding study of a GM derived corn in rats.

PMID- 23142392
TI  - We request a serious reconsideration of the recent paper by Seralini et al.
      alleging tumorigenesis in rats resulting from consumption of corn derived from
      crops improved through biotechnology (Seralini et al., 2012).

PMID- 23142393
TI  - Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically
      modified maize.

PMID- 23142394
TI  - Comments on "Long term toxicity of a Roundup herbicide and a Roundup-tolerant
      genetically modified maize".

PMID- 23142395
TI  - Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically
      modified maize.

PMID- 23142396
TI  - Serious inadequacies regarding the pathology data presented in the paper by
      Seralini et al. (2012).

PMID- 23142397
TI  - Response to original research article, in press, corrected proof, ''Long term
      toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified
      maize''.

PMID- 23142398
TI  - Toxicity of Roundup-tolerant genetically modified maize is not supported by
      statistical tests.

PMID- 23142399
TI  - WITHDRAWN: Letter to the editor.
AB  - This article has been withdrawn at the request of the author. The Publisher
      apologizes for any inconvenience this may cause. The full Elsevier Policy on
      Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 23142400
TI  - Intestinal transplantation: indications and prospects.
AB  - Intestinal transplantation (IT) can involve small bowel transplantation alone, or
      be associated with liver or multivisceral transplantation. Although IT is the
      radical treatment for intestinal failure, home parenteral nutrition (PN) remains
      the treatment of choice for this disease. Indications for IT are still debated. A
      recent study showed that early referral for IT is recommended for patients with
      life-threatening combined liver and intestinal failure or for patients with
      invasive intra-abdominal desmoid tumors. In the same study, no survival benefit
      was shown for patients undergoing IT for ultra-short bowel or major complications
      related to the PN catheter; indications still need to be fully assessed. While
      short-term outcomes for IT have improved dramatically (one-year survival for
      small bowel-alone IT is now 80% versus 0-28% in the 1980s), long-term outcomes
      have not improved much since the introduction of Tacrolimus in the 1990s: five
      year survival still does not exceed 60%. Some prospective developments could
      improve these results: the use of multivisceral grafts, the use of Sirolimus and
      Thymoglobulins in the immunosuppressive treatment, or the use of new biochemical
      markers for early diagnosis of graft rejection.

PMID- 23142401
TI  - What is the established contribution of laparoscopy in the treatment of rectal
      cancer?
AB  - The results of laparoscopic treatment of rectal cancer have been evaluated in
      several randomized trials. Still, the validity of this approach remains
      controversial because of concerns regarding its oncological safety. In this
      review, oncological results of laparoscopic rectal resection were similar to
      those of laparotomy, with no observed survival difference. Conversion from
      laparoscopy to laparotomy seemed to be associated with worse oncological results
      and an increased post-operative morbidity including nervous sequelae. Intra
      operative blood loss was significantly reduced with the laparoscopic approach,
      but post-operative morbidity was not different. Post-operative pain and length of
      hospital stay were decreased by the laparoscopic approach, and short-term quality
      of life was improved. There was no demonstration of significant reduction in late
      morbidity such as incisional hernia and bowel adhesions.

PMID- 23142402
TI  - Incidence and prevention of ventral incisional hernia.
AB  - OBJECTIVE: Ventral incisional hernia is a common complication of abdominal
      surgery. The incidence ranges from 2% to 20% and varies greatly from one series
      to another. The goal of this study was to determine the incidence, risk factors,
      and preventive measures for ventral incisional hernia. MATERIALS AND METHODS: An
      analysis of the surgical literature was performed using the search engines
      EMBASE, Cochrane Library, and PubMed with the keywords: abdominal hernia, wound
      dehiscence, incisional hernia, incidence, trocar site hernia, and hernia
      prevention. RESULTS: The overall incidence of incisional hernia after laparotomy
      was 9.9%. The incidence was significantly higher for midline incisions compared
      with transverse incisions (11% vs. 4.7%; P=0.006). In contrast, the incidence of
      ventral hernia was only 0.7% after laparoscopy. A compilation of all the studies
      comparing laparotomy to laparoscopy showed a significantly higher incidence of
      incisional hernia after laparotomy (P=0.001). Independent risk factors for
      incisional hernia included age and infectious complications. Only two meta
      analyses were able to show a significant decrease in risk-related to the use of
      non absorbable or slowly absorbable suture material. No difference in incisional
      hernia risk was shown with different suture techniques (11.1% for running suture,
      9.8% for interrupted sutures: NS). CONCLUSION: A review of the literature shows
      that only the choice of incisional approach (transverse incision or laparotomy
      vs. midline laparotomy) allows a significant decrease in the incidence of ventral
      incisional hernia.

PMID- 23142403
TI  - Clinical and endoscopic significance of bowel-wall thickening reported on
      abdominal computed tomographies in symptomatic patients with no history of
      gastrointestinal disease.
AB  - BACKGROUND: Bowel-wall thickening (BWT) is a commonly reported finding on
      diagnostic abdominal pelvic computed tomographies (CT) in patients with no
      history of gastroenterologic disease. The significance of this nonspecific
      finding is not clear. METHODS: Medical records from the Vancouver General
      Hospital were reviewed from October 27, 1999, to October 27, 2009. The initial
      search yielded 5696 cases, of which 76 cases met the inclusion criteria for
      review. Inclusion criteria were the following: age older than 18 years, symptoms
      without a diagnosis of gastrointestinal disease before CT, the reported finding
      of terminal ileal and/or colonic BWT, colonoscopy after CT, and/or microbiologic
      investigations. Exclusion criteria included known gastrointestinal disease before
      CT. The primary objective was to determine if BWT could be associated with a
      significant endoscopic pathology. The secondary objective was to determine
      whether the pattern of abnormality on the CT was associated with a specific
      endoscopic finding. RESULTS: A total of 76 patients met the inclusion criteria of
      our study. Of those, 76% had various identifiable pathologies on colonoscopy.
      Only 24% had normal colonoscopic findings. Inflammatory bowel disease (IBD) and
      infectious colitis were the most common causes of BWT. A report of "skip lesions"
      on the CT (5%) was always associated with IBD. "Pancolitis" reported on the CT
      (11%) was associated with endoscopic findings of IBD in 25% of cases, infection
      in 50% of cases, and normal findings in 25% of cases. The report of "stranding"
      (36%) on CT in the presence of BWT was associated with many non-neoplastic
      endoscopic pathologic processes, including infectious colitis (22%), IBD (19%),
      and ischemia (15%), but also was associated with normal endoscopic findings in
      26% of the cases. "Lymphadenopathy" was reported in 17% of the CTs and was
      associated with infectious colitis (30%), IBD (38%), or neoplastic processes
      (15%) but also normal endoscopic findings in 15%. CONCLUSION: Symptomatic
      patients who are found to have nonspecific BWT on CT should undergo definitive
      endoscopic investigation because the majority will have significant
      gastroenterologic disease, and only a minority will have a normal colonoscopy.

PMID- 23142404
TI  - Is there a need for improved Cryptosporidium diagnostics in Swedish calves?
AB  - Cryptosporidium parvum is a common pathogen in preweaned calves but in Sweden
      Cryptosporidium bovis, which is considered apathogenic, is the most common
      species in this age group and it has been identified in diarrhoeal samples,
      indicating that it could be a cause of diarrhoea. In routine diagnostic
      procedures, infection is determined by microscopy, which is not sufficient to
      differentiate these species. We investigated whether routine Cryptosporidium
      diagnostic procedures need improvement to include species determination. The
      relation of Cryptosporidium spp. and subtype with the clinical picture and other
      pathogens was also investigated. A total of 782 diarrhoeal calf samples were
      analysed and Cryptosporidium infection was diagnosed in 198 samples.
      Cryptosporidium parvum was identified in 178, C. bovis in six and mixed C.
      bovis/C. parvum in seven samples. Twenty-seven C. parvum subtypes were
      identified, of which 16 were newly described. Except for three herds, only one
      subtype per herd was identified. Cryptosporidium parvum-positive calves were
      younger than C. bovis-positive calves and most C. parvum infections were seen at
      1-3 weeks of age. Oocyst counts were higher in C. parvum samples. Yellow faecal
      colour was associated with C. parvum infection. Watery faeces had no greater
      association with C. parvum infection, but C. parvum subtype family IIa was more
      common than subtype family IId in watery faecal samples. No other pathogens were
      detected in the six C. bovis-infected calves, indicating a pathogenic potential.
      Our results show that species determination does not need to be included in
      routine Cryptosporidium diagnostic procedures in order to estimate the clinical
      relevance of infection in diarrhoeal calves. The maximum age when analysis for
      clinical cryptosporidiosis is performed can be lowered to 6 weeks of age.
      However, the indicated pathogenic potential of C. bovis warrants further
      attention.

PMID- 23142405
TI  - Association between medication use and adverse gastroenterologic events in
      patients receiving enteral nutrition therapy at a University Hospital.
AB  - INTRODUCTION: Enteral Nutrition Therapy (ENT) is considered an important tool for
      the appropriate maintenance of nutritional conditions. ENT tolerance may be
      limited due to gastrointestinal (GI) events resulting from formula composition
      and/or simultaneously administered drug therapies. AIMS: To verify the possible
      association between GI events and drug therapies being administered to patients
      receiving ENT at a university hospital. METHODS: A prospective observational
      cohort study was conducted. Medical records from 95 patients requiring ENT at the
      Hospital de Clinicas de Porto Alegre (HCPA) were randomly evaluated until
      discharge, death, or initiation of oral or parenteral diet occurred. Details of
      the administered medications and enteral formula, together with the presenting
      patient disease and digestive manifestations, were recorded by the medical team.
      Three experienced gastroenterologists evaluated the possible association between
      the digestive symptoms and the medications employed. The study protocol was
      approved by the HCPA Research Ethics Committee and patient consent forms were
      signed. RESULTS: Mean patient age: 65+/-17 (24-95) years; 94.70% presented with
      GI events: constipation 70.50%, diarrhea 38.90%, abdominal distension 18.90%,
      vomiting 16.80%, and pulmonary aspiration 1.10%. ENT was most indicated in
      neurologic (50.50%) and neoplastic (25.30%) disease. Medications given to the
      patients showed a positive relation: 63.20% to 86.70% of GI symptoms could be
      attributed to the drugs being administered. CONCLUSIONS: GI complications during
      ENT are common; they are frequently linked to administered drug therapy. Health
      care teams should consider all risk factors present, specifically those related
      to prescribed medication, before modifying/suspending ENT.

PMID- 23142406
TI  - [Clinicopathologic characteristics of 127 cases of gastroenteropancreatic
      neuroendocrine tumors (GEP-NETs) studied in an oncology hospital].
AB  - BACKGROUND: Neuroendocrine tumors (NETs) present all along the length of the
      gastrointestinal (GI) tract, from the esophagus to the anus, and they also
      present in the pancreas. AIMS: To classify NETs according to the WHO 2010
      criteria and to evaluate their anatomic distribution and clinicopathologic
      characteristics. MATERIAL AND METHODS: A search was carried out in the hospital
      pathology archives of all the cases diagnosed with carcinoid tumor and
      neuroendocrine carcinoma of the GI tract and pancreas studied over a period of 11
      years (1999-2010). The cases were reclassified according to the WHO 2010
      criteria. The clinical case records of each patient were reviewed. RESULTS: The
      study group was made up of 127 cases (68 men; 59 women). Age ranged from 24 to 85
      years with a median of 52 years. A total of 113 (89.00%) tumors occurred in the
      GI tract and 14 (11.00%) in the pancreas. Tumor size varied from 0.4cm to 9cm
      (median: 2.5cm). GI tumor histologic grades were: 54.00% grade 1; 31.00% grade 2;
      and 15.00% grade 3. Pancreatic tumor histologic grades were: 43.00% grade 1;
      36.00% grade 2; and 21.00% grade 3. Ki-67 overexpression was correlated with
      tumor grade (22.00% grade 3 vs 2.50% grade 1). CONCLUSIONS: Histologic grade of
      the gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is one of the most
      important prognostic factors. The term carcinoid should be eliminated because it
      does not reflect the biological behavior of these tumors.

PMID- 23142407
TI  - Gastrointestinal reactions in patients with enteral nutrition: are they related
      solely to this type of feeding or rather to the concomitant use of medications?

PMID- 23142408
TI  - Automatic facial responses to affective stimuli in high-functioning adults with
      autism spectrum disorder.
AB  - Individuals with autism spectrum disorder (ASD) demonstrate atypical behavioural
      responses to affective stimuli, although the underlying mechanisms remain
      unclear. Investigating automatic responses to these stimuli may help elucidate
      these mechanisms. 18 high-functioning adults with ASDs and 18 typically
      developing controls viewed 54 extreme pleasant (erotica), extreme unpleasant
      (mutilations), and non-social neutral images from the International Affective
      Picture System (IAPS). Two-thirds of images received an acoustic startle probe 3s
      post-picture onset. Facial electromyography (EMG) activity (orbicularis,
      zygomaticus, corrugator), skin conductance (SCR) and cardiac responses were
      recorded. The adults with ASDs demonstrated typical affective startle modulation
      and automatic facial EMG responses but atypical autonomic (SCRs and cardiac)
      responses, suggesting a failure to orient to, or a deliberate effort to
      disconnect from, socially relevant stimuli (erotica, mutilations). These results
      have implications for neural systems known to underlie affective processes,
      including the orbitofrontal cortex and amygdala.

PMID- 23142409
TI  - Detection of Aspergillus fumigatus pulmonary fungal infections in mice with
      (99m)Tc-labeled MORF oligomers targeting ribosomal RNA.
AB  - PURPOSE: Invasive aspergillosis is a major cause of infectious morbidity and
      mortality in immunocompromised patients. The fungus Aspergillus fumigatus (A.
      fumigatus) is the primary causative agent of invasive aspergillosis. However, A.
      fumigatus infections remain difficult to diagnose particularly in the early
      stages due to the lack of a rapid, sensitive and specific diagnostic approach. In
      this study, we investigated (99m)Tc labeled MORF oligomers targeting fungal
      ribosomal RNA (rRNA) for the imaging detection of fungal infections. PROCEDURES:
      Three phosphorodiamidate morpholino (MORF) oligomer (a DNA analogue) probes were
      designed: AGEN, complementary to a sequence of the fungal 28S ribosomal RNA
      (rRNA) of Aspergillus, as a genus-specific probe; AFUM, complementary to the 28S
      rRNA sequence of A. fumigatus, as a fungus species-specific probe; and cMORF,
      irrelevant to all fungal species, as a control probe. The probes were conjugated
      with Alexa Fluor 633 carboxylic acid succinimidyl ester (AF633) for fluorescence
      imaging or with NHS-mercaptoacetyl triglycine (NHS-MAG3) for nuclear imaging with
      (99m)Tc and then evaluated in vitro and in vivo. RESULTS: The specific binding of
      AGEN and AFUM to fungal total RNA was confirmed by dot blot hybridization while
      specific binding of AGEN and AFUM in fixed and live A. fumigatus was demonstrated
      by both fluorescent in situ hybridization (FISH) analysis and accumulation in
      live cells. SPECT imaging of BALB/c mice with pulmonary A. fumigatus infections
      and administered (99m)Tc labeled AGEN and AFUM showed immediate and obvious
      accumulation in the infected lungs, while no significant accumulation of the
      control (99m)Tc-cMORF in the infected lung was observed. Compared to non-infected
      mice, with sacrifice at 1h, the accumulation of (99m)Tc-AGEN and (99m)Tc-AFUM in
      the lungs of mice infected with A. fumigatus was 2 and 2.7 fold higher
      respectively. CONCLUSIONS: In vivo targeting fungal ribosomal RNA with (99m)Tc
      labeled MORF probes AGEN and AFUM may be useful for A. fumigatus infection
      imaging and may provide a new strategy for the noninvasive diagnosis of invasive
      aspergillosis and other fungal infections.

PMID- 23142410
TI  - 99Mo/(99m)Tc separation: an assessment of technology options.
AB  - Several strategies for the effective separation of (99m)Tc from (99)Mo have been
      developed and validated. Due to the success of column chromatographic separation
      using acidic alumina coupled with high specific activity fission (99)Mo (F
      (99)Mo) for production of (99)Mo/(99m)Tc generators, however, most technologies
      until recently have generated little interest. The reduced availability of F
      (99)Mo and consequently the shortage of (99)Mo/(99m)Tc column generators in the
      recent past have resurrected interest in the production of (99)Mo as well as
      (99m)Tc by alternate routes. Most of these alternative production processes
      require separation techniques capable of providing clinical grade (99m)Tc from
      low specific activity (99)Mo or irradiated Mo targets. For this reason there has
      been renewed interest in alternate separation routes. This paper reviews the
      reported separation technologies which include column chromatography, solvent
      extraction, sublimation and gel systems that have been traditionally used for the
      fabrication of (99)Mo/(99m)Tc generator systems. The comparative advantage,
      disadvantage, and technical challenges toward adapting the emerging requirements
      are discussed. New developments such as solid-phase column extraction,
      electrochemical separation, extraction chromatography, supported liquid membrane
      (SLM) and thermochromatographic techniques are also being evaluated for their
      potential application in the changed scenario of providing (99m)Tc from alternate
      routes. Based on the analysis provided in this review, it appears that some
      proven separation technologies can be quickly resurrected for the separation of
      clinical grade (99m)Tc from macroscopic levels of reactor or cyclotron irradiated
      molybdenum targets. Furthermore, emerging technologies can be developed further
      to respond to the expected changing modes of (99m)Tc production.

PMID- 23142411
TI  - Insights into the function of RifI2: structural and biochemical investigation of
      a new shikimate dehydrogenase family protein.
AB  - The shikimate dehydrogenase (SDH) family consists of enzymes with diverse roles
      in secondary metabolism. The two most widespread members of the family, AroE and
      YdiB, function in amino acid biosynthesis and quinate catabolism, respectively.
      Here, we have determined the crystal structure of an SDH homolog belonging to the
      RifI class, a group of enzymes with proposed roles in antibiotic biosynthesis.
      The structure of RifI2 from Pseudomonas putida exhibits a number of distinctive
      features, including a substantial C-terminal truncation and an atypical mode of
      oligomerization. The active site of the enzyme contains substrate- and cofactor
      binding motifs that are significantly different from those of any previously
      characterized member of the SDH family. These features are reflected in the novel
      kinetic properties of the enzyme. RifI2 exhibits much lower activity using
      shikimate as a substrate than AroE, and a strong preference for NAD(+) instead of
      NADP(+) as a cofactor. Moreover, the enzyme has only trace activity using
      quinate, unlike YdiB. Cocrystallization of RifI2 with NAD(+) provided the
      opportunity to determine the mode of cofactor selectivity employed by the enzyme.
      We complemented this analysis by probing the role of a strictly conserved residue
      in the cofactor-binding domain, Asn193, by site directed mutagenesis. This study
      presents the first crystal structure and formal kinetic characterization of a new
      NAD(+)-dependent member of the SDH family.

PMID- 23142412
TI  - Estimated preejection period (PEP) based on the detection of the R-wave and dZ/dt
      min peaks does not adequately reflect the actual PEP across a wide range of
      laboratory and ambulatory conditions.
AB  - The current study evaluates the validity of the PEP computed from a fixed value
      for the Q-wave onset to R-wave peak (QR) interval and an R-wave peak to B-point
      (RB) interval that is estimated from the R-peak to dZ/dt-min peak (ISTI)
      interval. Ninety-one subjects participated in a 90min laboratory experiment in
      which a variety of often employed physical and mental stressors were presented
      and 31 further subjects participated in a structured 2hour ambulatory recording
      in which they partook in natural activities that induced large variation in
      posture and physical activity. PEP, QR interval, and ISTI were scored and
      rigorously checked by interactive inspection. Across the very diverse laboratory
      and ambulatory conditions the QR interval could be approximated by a fixed
      interval of 40ms but 95% confidence intervals were large (25.5 to 54.5ms).
      Multilevel analysis showed that 79% to 81% of the within and between-subject
      variation in the RB interval could be predicted by the ISTI with a simple linear
      regression equation. However, the optimal intercept and slope values in this
      equation varied significantly across subjects and study setting. Bland Altman
      plots revealed a large discrepancy between the estimated PEP using the R-wave
      peak and dZ/dt-min peak and the actual PEP based on the Q-wave onset and B-point.
      We conclude that the PEP estimated from a fixed QR interval and the ISTI could be
      a useful addition to the psychophysiologist's toolbox, but that it cannot replace
      the actual PEP to index cardiac sympathetic control.

PMID- 23142414
TI  - Field cancerization in mammary carcinogenesis - Implications for prevention and
      treatment of breast cancer.
AB  - The natural history of breast cancer unfolds with the development of ductal
      carcinoma in situ (DCIS) in normal breast tissue, and evolution of this pre
      invasive neoplasm into invasive cancer. The mechanisms that drive these processes
      are poorly understood, but evidence from the literature suggests that mammary
      carcinogenesis may occur through the process of field cancerization. Clinical
      observations are consistent with the idea that (i) DCIS may arise in a field of
      altered breast epithelium, (ii) narrow surgical margins do not remove the entire
      altered field (contributing to recurrence and/or disease progression), and (iii)
      whole-breast radiation therapy is effective in elimination of the residual field
      of altered cells adjacent to the resected DCIS. Molecular studies suggest that
      the field of altered breast epithelial cells may carry cancer-promoting genetic
      mutations (or other molecular alterations) or cancer promoting epimutations
      (oncogenic alterations in the epigenome). In fact, most breast cancers develop
      through a succession of molecular events involving both genetic mutations and
      epimutations. Hence, in hereditary forms of breast cancer, the altered field
      reflects the entire breast tissue which is composed of cells with a predisposing
      molecular lesion (such as a BRCA1 mutation). In the example of a BRCA1-mutant
      patient, it is evident that local resection of a DCIS lesion or localized but
      invasive cancer will not result in elimination of the altered field. In sporadic
      breast cancer patients, the mechanistic basis for the altered field may not be so
      easily recognized. Nonetheless, identification of the nature of field
      cancerization in a given patient may guide clinical intervention. Thus, patients
      with DCIS that develops in response to an epigenetic lesion (such as a
      hypermethylation defect affecting the expression of tumor suppressor genes) might
      be treated with epigenetic therapy to normalize the altered field and reduce the
      risk of secondary occurrence of DCIS or progression to invasive cancer.

PMID- 23142415
TI  - Daily roadside BTEX concentrations in East Asia measured by the Lanwatsu,
      Radiello and Ultra I SKS passive samplers.
AB  - A new home-made diffusive bag-type passive sampler called Lanwatsu was developed
      for benzene, toluene, ethylbenzene and xylene monitoring in roadside air. The
      passive samplers were outdoor validated and deployed together with two commercial
      passive samplers, Ultra I SKC Inc. and Radiello, for daily roadside air
      monitoring in East Asian cities including HoChiMinh, Hanoi, Cantho, Danang,
      Vungtau, Hue (Vietnam), Kuala Lumpur (Malaysia), Kyoto, Osaka (Japan), Nanjing
      (China) and Singapore in 2011. High daily benzene concentrations of 87, 52, 32,
      23, 13, 12 and 48 ug/m3 were observed in HoChiMinh, Hanoi, Cantho, Danang, Hue,
      Vung Tau (Vietnam), and Kuala Lumpur (Malaysia), respectively. Kyoto and Osaka
      (Japan) were clean with daily benzene concentrations below 2.3 MUg/m3. The daily
      benzene concentrations in Nanjing (China) and Singapore were 5.6 and 6.9 MUg/m3,
      respectively. The three passive samplers were equivalent. Passive sampling by the
      Lanwatsu passive sampler is acceptable for daily outdoor benzene monitoring.

PMID- 23142416
TI  - Culturable microbial groups and thallium-tolerant fungi in soils with high
      thallium contamination.
AB  - Thallium (Tl) contamination in soil exerts a significant threat to the ecosystem
      health due to its high toxicity. However, little is known about the effect of Tl
      on the microbial community in soil. The present study aimed at characterizing the
      culturable microbial groups in soils which experience for a long time high Tl
      contamination and elevated Hg and As. The contamination originates from As, Hg
      and Tl sulfide mineralization and the associated mining activities in the Guizhou
      Province, Southwest China. Our investigation showed the existence of culturable
      bacteria, filamentous fungi and actinomyces in long-term Tl-contaminated soils.
      Some fungal groups grow in the presence of high Tl level up to 1000 mg kg-1. We
      have isolated and identified nine Tl-tolerant fungal strains based on the
      morphological traits and ITS analysis. The dominant genera identified were
      Trichoderma, Penicillium and Paecilomyces. Preliminary data obtained in this
      study suggested that certain microbes were able to face high Tl pollution in soil
      and maintain their metabolic activities and resistances. The highly Tl-tolerant
      fungi that we have isolated are potentially useful in the remediation of Tl
      contaminated sites.

PMID- 23142413
TI  - Risk factors for hospital readmission of elderly patients.
AB  - BACKGROUND: The aim of this study was to identify which factors were associated
      with a risk of hospital readmission within 3 months after discharge of a sample
      of elderly patients admitted to internal medicine and geriatric wards. METHODS:
      Of the 1178 patients aged 65 years or more and discharged from one of the 66
      wards of the 'Registry Politerapie SIMI (REPOSI)' during 2010, 766 were followed
      up by phone interview 3 months after discharge and were included in this
      analysis. Univariate and multivariate logistic regression models were used to
      evaluate the association of several variables with rehospitalization within 3
      months from discharge. RESULTS: Nineteen percent of patients were readmitted at
      least once within 3 months after discharge. By univariate analysis in-hospital
      clinical adverse events (AEs), a previous hospital admission, number of diagnoses
      and drugs, comorbidity and severity index (according to Cumulative Illness Rating
      Scale-CIRS), vascular and liver diseases with a level of impairment at discharge
      of 3 or more at CIRS were significantly associated with risk of readmission.
      Multivariate logistic regression analysis showed that only AEs during
      hospitalization, previous hospital admission, and vascular and liver diseases
      were significantly associated with the likelihood of readmission. CONCLUSIONS:
      The results demonstrate the need for increased medical attention towards elderly
      patients discharged from hospital with characteristics such as AEs during the
      hospitalization, previous admission, vascular and liver diseases.

PMID- 23142418
TI  - Mitochondrial dynamics and physiology.

PMID- 23142419
TI  - Characterization of global metabolic responses of glucose-6-phosphate
      dehydrogenase-deficient hepatoma cells to diamide-induced oxidative stress.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) is crucial to NADPH generation and redox
      homeostasis. We have recently shown that G6PD deficiency predisposes cells to
      oxidant-induced cell death, and it is associated with the impairment of
      glutathione regeneration. It remains unclear what other metabolic pathways are
      affected by G6PD deficiency and whether the altered metabolism disturbs cellular
      redox homeostasis and underlies increased susceptibility to oxidants. In this
      study, we examined the effects of diamide on global metabolite profiles of SK
      Hep1-derived SK-i-Gi and SK-i-Sc cells, which could inducibly express short
      hairpin RNA (shRNA) against G6PD (Gi) and control shRNA (Sc), respectively. There
      was no significant difference in their metabolite profiles under uninduced
      conditions. Doxycycline (Dox) addition resulted in over 70% decrease in G6PD
      activity in SK-i-Gi cells. This was accompanied by relatively minor changes in
      the metabolome of SK-i-Gi cells. Upon further diamide treatment, the metabolite
      profiles of both SK-i-Gi and SK-i-Sc cells changed in a time-dependent manner. A
      number of metabolic pathways, including those involved in energy metabolism and
      metabolism of amino acids and glutathione, were affected. However, the changes in
      the metabolite profile of Dox-treated SK-i-Gi cells were distinct from those of
      control cells (i.e., Dox-treated SK-i-Sc, SK-i-Gi, and SK-i-Sc cells). Cellular
      glutathione was depleted, whereas its disulfide form increased significantly in
      diamide, Dox-treated SK-i-Gi cells. Metabolites related to energy metabolism,
      such as AMP, ADP, and acetylcarnitine, increased to a greater extent in these
      cells than in diamide-treated control cells. In contrast, NAD and glutathione
      dropped to lower levels in SK-i-Gi cells than in control cells. The NAD(+)
      depletion in SK-i-Gi cells was accompanied by a significant increase in NAD
      kinase activity. Targeted analyses revealed that NADP(+) and NADPH increased
      significantly in diamide, Dox-treated SK-i-Gi cells compared with similarly
      treated control cells. Our results suggest that diamide induces oxidation and
      depletion of glutathione in SK-i-Gi cells under conditions of G6PD shRNA
      induction and subsequently induces conversion of NAD(+) to NADP(+) through
      enhanced NAD kinase activity. This may represent a compensatory mechanism to
      restore cellular NADPH reserve in G6PD-deficient cells. It is accompanied by
      alteration in pathways of cellular energy metabolism, such as glycolysis and beta
      oxidation.

PMID- 23142417
TI  - The role of default network deactivation in cognition and disease.
AB  - A considerable body of evidence has accumulated over recent years on the
      functions of the default-mode network (DMN)--a set of brain regions whose
      activity is high when the mind is not engaged in specific behavioral tasks and
      low during focused attention on the external environment. In this review, we
      focus on DMN suppression and its functional role in health and disease,
      summarizing evidence that spans several disciplines, including cognitive
      neuroscience, pharmacological neuroimaging, clinical neuroscience, and
      theoretical neuroscience. Collectively, this research highlights the functional
      relevance of DMN suppression for goal-directed cognition, possibly by reducing
      goal-irrelevant functions supported by the DMN (e.g., mind-wandering), and
      illustrates the functional significance of DMN suppression deficits in severe
      mental illness.

PMID- 23142420
TI  - Allelic variants of glutathione S-transferase P1-1 differentially mediate the
      peroxidase function of peroxiredoxin VI and alter membrane lipid peroxidation.
AB  - The dual-functioning antioxidant enzyme peroxiredoxin VI (Prdx6) detoxifies lipid
      peroxides particularly in biological membranes, and its peroxidase function is
      activated by glutathione S-transferase Pi (GSTP). The GSTP gene is polymorphic in
      humans, with the wild-type GSTP1-1A (Ile105, Ala114) and three variants: GSTP1-1B
      (Ile105Val, Ala114), GSTP1-1C (Ile105Val, Ala114Val), and GSTP1-1D (Ile105,
      Ala114Val). The focus of this study was to determine the influence of these
      polymorphisms on Prdx6 peroxidase function. Using extracellular generation of OH
      radicals and fluorescence (DPPP dye) detection, we found a fast (~300 s) onset of
      lipid peroxidation in membranes of MCF-7 cells transfected with a catalytically
      inactive Y7F mutant of GSTP1-1 and either GSTP1-1B or GSTP1-1D. However, this
      effect was not detected in cells expressing either GSTP1-1A or GSTP1-1C. Imaging
      of DPPP-labeled MCF-7 cells showed fluorescence localized in the plasma membrane,
      but intensity was substantially diminished in the GSTP1-1A- and GSTP1-1C
      expressing cells. Moreover, in the Y7F mutant of GSTP1-1A-, GSTP1-1B-, and GST1
      1D-expressing cells ()OH generation resulted (after 36 h) in plasma membrane
      permeability-related cell death, whereas GSTP1-1A- and GSTP1-1C-expressing cells
      had significantly better survival. We used FRET analyses to measure in vitro
      binding of purified GSTP1-1 allelic variant proteins to purified recombinant
      Prdx6. The affinities for Prdx6 binding to GSH-loaded GSTP1-1's either mirrored
      their observed peroxidase activities (using phospholipid hydroperoxide as a
      substrate), GSTP1-1A>GSTP1-1C (K(D)=51.0 vs 57.0 nM), or corresponded to
      inactivation, GSTP1-1B (GSTP1-1D) (K(D)=101.0 (94.0) nM). In silico modeling of
      the GSTP1-1-Prdx6 heterodimer revealed that the sites of GSTP1-1 polymorphism
      (Ile105 and Ala114) are in close proximity to the binding interface. Thus, there
      is a hierarchy of effectiveness for polymorphic variants of GSTP1-1 to regulate
      Prdx6 peroxidase function, a feature that may influence human population
      susceptibilities to oxidant stress.

PMID- 23142421
TI  - Chitosan microspheres as an alveolar macrophage delivery system of ofloxacin via
      pulmonary inhalation.
AB  - Because Mycobacterium tuberculosis, which causes tuberculosis, survives mainly in
      the alveolar macrophages, the remedial efficiency of anti-tuberculosis drugs such
      as ofloxacin may be improved by their direct delivery to the lungs via pulmonary
      inhalation. For this purpose, ofloxacin-loaded, glutaraldehyde-crosslinked
      chitosan microspheres (OCMs) were prepared using a water-in-oil emulsification
      method. The particle size of the OCMs was around 1-6 MUm, and the content of
      ofloxacin was 27% (w/w). A twin-stage impinger (TSI) study revealed that the
      device-removal efficiency of the drug from the capsule and the arrival rate of
      the drug to stage II of the apparatus were substantially improved for OCMs
      compared to ofloxacin itself (i.e., 81 vs. 98% and 13 vs. 45%, respectively).
      Also, the in vitro uptake of ofloxacin from the OCMs to alveolar macrophages
      (NR8383) was substantially accelerated: the cellular ofloxacin concentrations at
      4 and 24 h after the application were >3.5-fold greater than those for free
      ofloxacin. The above results indicate that pulmonary inhalation of OCMs might
      improve the delivery efficiency of ofloxacin to the alveolar macrophages, thereby
      shortening the length of time that is required to cure tuberculosis with the drug
      usually at least 6 months when administered orally.

PMID- 23142422
TI  - Animal models of autism with a particular focus on the neural basis of changes in
      social behaviour: an update article.
AB  - Research on autism has been gaining more and more attention. However, its
      aetiology is not entirely known and several factors are thought to contribute to
      the development of this neurodevelopmental disorder. These potential contributing
      factors range from genetic heritability to environmental effects. A significant
      number of reviews have already been published on different aspects of autism
      research as well as focusing on using animal models to help expand current
      knowledge around its aetiology. However, the diverse range of symptoms and
      possible causes of autism have resulted in as equally wide variety of animal
      models of autism. In this update article we focus only on the animal models with
      neurobehavioural characteristics of social deficit related to autism and present
      an overview of the animal models with alterations in brain regions,
      neurotransmitters, or hormones that are involved in a decrease in sociability.

PMID- 23142423
TI  - Superoxide generation in different brain regions of rats during normoxia and
      hypoxia-reoxygenation.
AB  - The superoxide-dependent chemiluminescent intensity in different brain regions
      was examined in ex vivo tissue slices of rat brain during normoxia and hypoxia
      reoxygenation with lucigenin. The chemiluminescent intensity increased during
      reoxygenation after hypoxic treatment. There was a higher level of
      chemiluminescent intensity in the hippocampus during normoxia, and a lower level
      in the white matter during normoxia and hypoxia-reoxygenation. A weak correlation
      was found between the chemiluminescent intensity and the glucose uptake rate
      during normoxia. Then we examined whether hypoxic strength correlates to
      superoxide generation. The chemiluminescent intensity increased in a hypoxic
      strength-dependent manner. The generation mechanism of superoxide was examined
      using carbonyl cyanide m-chlorophenylhydrazone (CCCP), a mitochondrial uncoupler,
      genipin, an inhibitor for uncoupling protein-2, alloprinol, a xanthine oxidase
      inhibitor, or apocynin, an NADPH oxidase inhibitor. The chemiluminescent signal
      was significantly inhibited by CCCP under normoxic condition and enhanced by
      genipin during normoxia and hypoxia-reoxygenation, but not by allopurinol or
      apocynin. These results suggest that superoxide generation is high in the
      hippocampus during normoxia and low in the white matter during normoxia and
      hypoxia-reoxygenation, superoxide generation in the hypoxia-reoxygenation brain
      correlates with the strength of hypoxia influenced by oxygen delivery, and
      mitochondrion is the major sites of intracellular superoxide generation.

PMID- 23142424
TI  - Urea is not a universal cryoprotectant among hibernating anurans: evidence from
      the freeze-tolerant boreal chorus frog (Pseudacris maculata).
AB  - Freeze-tolerant organisms accumulate a diversity of low molecular weight
      compounds to combat negative effects of ice formation. Previous studies of anuran
      freeze tolerance have implicated urea as a cryoprotectant in the wood frog
      (Lithobates sylvatica). However, a cryoprotective role for urea has been
      identified only for wood frogs, though urea accumulation is an evolutionarily
      conserved mechanism for coping with osmotic stress in amphibians. To identify
      whether multiple solutes are involved in freezing tolerance in the boreal chorus
      frog (Pseudacris maculata), we examined seasonal and freezing-induced variation
      in several potential cryoprotectants. We further tested for a cryoprotective role
      for urea by comparing survival and recovery from freezing in control and urea
      loaded chorus frogs. Tissue levels of glucose, urea, and glycerol did not vary
      significantly among seasons for heart, liver, or leg muscle. Furthermore, no
      changes in urea or glycerol levels were detected with exposure to freezing
      temperatures in these tissues. Urea-loading increased tissue urea concentrations,
      but failed to enhance freezing survival or facilitate recovery from freezing in
      chorus frogs in this study, suggesting little role for urea as a natural
      cryoprotectant in this species. These data suggest that urea may not universally
      serve as a primary cryoprotectant among freeze-tolerant, terrestrially
      hibernating anurans.

PMID- 23142425
TI  - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) metabolism-related enzymes
      gene polymorphisms, NNK metabolites levels and urothelial carcinoma.
AB  - Gene polymorphisms of the 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)
      metabolism-related enzymes-cytochrome P450 (CYP) monooxygenase 2A13 (CYP2A13) and
      UDP-glucuronosyltransferases (UGT)-2B7 could contribute to the levels of NNK
      related metabolites in urine, thereby increasing the susceptibility to urothelial
      carcinoma (UC). Therefore, our study aimed to evaluate the roles of two gene
      polymorphisms (CYP2A13 and UGT2B7) of NNK metabolism-related enzymes in the
      carcinogenesis of UC in Taiwan. A hospital-based pilot case-control study was
      conducted. There were 121 UC cases and 121 age- and sex-matched healthy
      participants recruited from March 2007 to April 2009. Urine samples were analyzed
      for NNK-related metabolites using the liquid chromatography-tandem mass
      spectrometry method. Genotyping was conducted using a polymerase chain reaction
      restriction fragment length polymorphism technique. ANCOVA and multivariate
      logistic regression were applied for data analyses. In healthy controls, former
      smokers had significantly higher total NNAL and higher NNAL-Gluc than never
      smokers or current smokers. Subjects carrying the UGT2B7 268 His/Tyr or Tyr/Tyr
      genotype had significantly lower total NNAL than those carrying His/His genotype.
      However, no association was seen between gene polymorphisms of CYP2A13 and UGT2B7
      and UC risk after adjustment for age and sex. Significant dose -response
      associations between total NNAL, free NNAL, the ratios of free NNAL/total NNAL
      and NNAL-Gluc/total NNAL and UC risk were observed. In the future, large-scale
      studies will be required to verify the association between the single nucleotide
      polymorphisms of NNK metabolism-related enzymes and UC risk.

PMID- 23142426
TI  - Reprint of: Characterising hepatic mitochondrial function as a model for systemic
      toxicity: a commentary.
AB  - A major challenge in toxicology is the development of non-animal methods for the
      assessment of human health risks that might result from repeated systemic
      exposure. We present here a perspective that considers the opportunities that
      computational modelling methods may offer in addressing this challenge. Our
      approach takes the form of a commentary designed to inform responses to future
      calls for research in predictive toxicology. It is considered essential that
      computational model-building activities be at the centre of the initiative,
      driving an iterative process of development, testing and refinement. It is
      critical that the models provide mechanistic understanding and quantitative
      predictions. The aim would be to predict effects in humans; in order to help
      define a challenging but yet feasible initial goal the focus would be on liver
      mitochondrial toxicity. This will inevitably present many challenges that
      naturally lead to a modular approach, in which the overall problem is broken down
      into smaller, more self-contained sub-problems that will subsequently need to be
      connected and aligned to develop an overall understanding. The project would
      investigate multiple modelling approaches in order to encourage links between the
      various disciplines that hitherto have often operated in isolation. The project
      should build upon current activities in the wider scientific community, to avoid
      duplication of effort and to ensure that investment is maximised. Strong
      leadership will be required to ensure alignment around a set of common goals that
      would be derived using a problem-statement driven approach. Finally, although the
      focus here is on toxicology, there is a clear link to the wider challenges in
      systems medicine and improving human health.

PMID- 23142427
TI  - Ionic matrices pre-spotted matrix-assisted laser desorption/ionization plates for
      patient maker following in course of treatment, drug titration, and MALDI mass
      spectrometry imaging.
AB  - In the current study, we compared plastic matrix-assisted laser
      desorption/ionization (MALDI) plates pre-spotted with different solid ionic
      matrices. Data reflect that after 3 months of storage, the standards were
      oxidized in alpha-cyano-4-hydroxycinnamic acid (HCCA) whether or not in HCCA/3
      acetylpyridine (3APY) and HCCA/aniline, and certain peptides, such as ubiquitin,
      were not detected using the HCCA matrix, whereas they were detected in pre
      spotted ionic matrices. Application in peptidomics of these MALDI matrices pre
      spotted plates (after 3 months of storage) with ovarian cyst fluid showed less
      intense signals with HCCA than with solid ionic matrices. We show that these pre
      spotted ionic matrices plates can be used for relative drug quantification, high
      mass protein detection, and MALDI mass spectrometry imaging.

PMID- 23142428
TI  - Electrochemiluminescent assay for detection of extremely rare mutations based on
      ligase reaction and bead enrichment.
AB  - The detection of rare mutations is particularly essential in many areas of
      biomedical research. Here, we report an ultrasensitive method to detect extremely
      rare point mutations based on electrochemiluminescent assay. The point mutation
      among large excess wild-type alleles is exclusively amplified through ligase
      detection reaction. The products corresponding to the amplification of mutant
      alleles are selectively captured by magnetic beads and then labeled with
      electrochemiluminescent substrates. Thus, point mutations with a percentage as
      small as 0.01% in the DNA population can be detected by electrochemiluminescent
      assay. Moreover, because the electrochemiluminescent signal of the mutation is
      proportional to the percentage of mutant alleles in the DNA population, the
      percentage of mutant alleles can be roughly accessed.

PMID- 23142429
TI  - Monitoring temperature with fluorescence during real-time PCR and melting
      analysis.
AB  - Accurate control of the sample temperature during thermal cycling is critical for
      successful polymerase chain reaction (PCR). Direct sensor contact with the
      reaction is problematic, forcing measurements external to the sample and
      compromising accuracy during rapid temperature transitions. The widespread use of
      fluorescence in real-time PCR and melting analysis suggests another measure of
      temperature, the intrinsic fluorescence of temperature-sensitive passive dyes.
      Calibration curves correlating sulforhodamine B fluorescence to temperature on
      nine real-time PCR instruments were obtained by heating at 0.018-0.1  degrees C/s
      between 50 and 95  degrees C, with a twofold change in fluorescence. After
      instrument stabilization for 20 min, no dye photobleaching was observed and
      thermal degradation was 2.2%/h at 80  degrees C. During cycling, solution
      temperatures derived from fluorescence were well matched to thermocouples placed
      within samples, but not to temperatures recorded by the instrument. Solution
      temperatures lagged instrument temperatures by up to 8  degrees C during cycling,
      often requiring 5-10 s at target temperatures for equilibration. Melting curves
      were displaced by 0.2-1.1  degrees C. Temperature inaccuracies were dependent on
      the instrument, the ramp rate, and the sample volume. The fluorescence of passive
      dyes can be used to accurately assess solution temperatures during PCR and should
      be particularly useful at fast cycling speeds.

PMID- 23142430
TI  - A scalable method for O-antigen purification applied to various Salmonella
      serovars.
AB  - The surface lipopolysaccharide of gram-negative bacteria is both a virulence
      factor and a B cell antigen. Antibodies against O-antigen of lipopolysaccharide
      may confer protection against infection, and O-antigen conjugates have been
      designed against multiple pathogens. Here, we describe a simplified methodology
      for extraction and purification of the O-antigen core portion of Salmonella
      lipopolysaccharide, suitable for large-scale production. Lipopolysaccharide
      extraction and delipidation are performed by acetic acid hydrolysis of whole
      bacterial culture and can take place directly in a bioreactor, without previous
      isolation and inactivation of bacteria. Further O-antigen core purification
      consists of rapid filtration and precipitation steps, without using enzymes or
      hazardous chemicals. The process was successfully applied to various Salmonella
      enterica serovars (Paratyphi A, Typhimurium, and Enteritidis), obtaining good
      yields of high-quality material, suitable for conjugate vaccine preparations.

PMID- 23142431
TI  - 'A good midwife stands out': 3rd year midwifery students' views.
AB  - BACKGROUND: the midwifery workforce in Australia is ageing and predominantly part
      time. There is considerable interest in the induction and retention of new
      midwives in the profession. OBJECTIVE: this study was undertaken to explore 3rd
      year students' views of the good midwife. It was anticipated that student views
      would show evidence of early transition and socialisation into the profession.
      DESIGN: qualitative thematic analysis. SETTING: Melbourne, Australia
      PARTICIPANTS: all completing midwifery students, in 2010, were invited to
      participate (n=31). FINDINGS: three broad themes emerged from the analysis: (1) a
      skilled practitioner; (2) a caring and compassionate individual; and (3) beyond
      the call of duty: passion and enthusiasm for midwifery. KEY CONCLUSIONS AND
      IMPLICATIONS FOR PRACTICE: it was evident that 3rd year students' views of the
      good midwife were becoming aligned with the views of qualified midwives. Students
      also acknowledged the importance of safe practice at the same time as supporting
      women to make decisions. However, their intense passion and enthusiasm for
      midwifery practice may make them vulnerable to disappointment with the
      profession.

PMID- 23142432
TI  - A qualitative study of infant feeding decisions among low-income women in the
      Republic of Ireland.
AB  - OBJECTIVE: to explore infant feeding decisions among low-income women living in
      Ireland to gain an in-depth understanding of the factors, which influence breast
      feeding initiation and continuation. DESIGN: a descriptive qualitative study
      using focus groups and semi-structured interviews. SETTING: community and primary
      health-care settings in the Republic of Ireland. PARTICIPANTS: a convenience
      sample of 33 low-income mothers was recruited from 2 community programmes and 3
      primary health-care centres. FINDINGS: six dominant themes were identified using
      Thematic Analysis. Prior knowledge of infant feeding, especially from experiences
      of seeing breast- and artificial milk-feeding in the family and the community,
      influenced feeding choice. Embarrassment and stigma about breast feeding in
      public places and in some cases in the private sphere were commonly described as
      barriers to breast feeding. The decision to bottle feed often reflected a
      balancing of the needs of the mother and the baby, because breast feeding was
      often perceived as inconvenient and requiring extreme determination. Breast
      feeding difficulties in the early weeks were frequently described and those who
      stopped breast feeding early often lacked practical knowledge and experienced
      support. In terms of health professional support, the mothers favoured a non
      pressurised approach along with practical help with breast feeding. KEY
      CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: there is a need for promotional
      efforts to normalise breast feeding and for training of health professionals in
      the provision of appropriate support.

PMID- 23142433
TI  - Application of Resource Utilization in Dementia (RUD) instrument in a global
      setting.
AB  - BACKGROUND: The Resource Utilization in Dementia (RUD) questionnaire is the most
      widely used instrument for resource use data collection in dementia, enabling
      comparison of costs of care across countries with differing health care
      provisions. Recent feedback from payers questioned its face validity given that
      health care provisions have changed since the initial development of the RUD in
      1998. The aim of this study was to update the RUD to improve its face validity in
      Alzheimer's disease (AD) clinical research and its utility for health care
      resource allocation. METHODS: An extensive PubMed review was conducted of current
      relevant resource items in AD in 15 countries. The findings were complemented by
      interviews with local care providers and experts in dementia care and health
      economics. Their proposed revisions were discussed with five leading dementia
      experts in North and South America, northern and southern Europe, and Asia. A new
      version of the RUD was developed based on their recommendations. RESULTS: RUD
      users identified a need for more information relevant to coverage decisions.
      Proposed revisions included changes to existing questions (e.g., to capture more
      accurately the number and type of health care visits) and the addition of new
      questions (e.g., on informal caregiver hours and the primary caregiver's hours of
      sleep). CONCLUSION: Several minor changes were made to the RUD instrument to
      improve the accuracy and precision of the data while maintaining comparability
      with the original version and reflecting current medical practice. The RUD
      Complete Version 4.0 is now available for use in future AD clinical trials.

PMID- 23142434
TI  - Renin-angiotensin system blockers affect cognitive decline and serum
      adipocytokines in Alzheimer's disease.
AB  - BACKGROUND: Accumulating evidence indicates an association of Alzheimer's disease
      (AD) with the metabolic syndrome (MetS), characterized by visceral fat
      accumulation with insulin resistance and altered secretion of adipocytokines such
      as adiponectin and leptin. The renin-angiotensin system (RAS) regulates blood
      pressure and insulin resistance. Recent studies suggest that the RAS plays
      crucial roles in cognitive functions and that adipocytokines exert
      neuroprotective activity in the brain. We investigated whether RAS blockers
      (RASB) affect adipocytokines and cognitive function in patients with AD. METHODS:
      We studied 78 patients with a diagnosis of probable AD according to the
      Diagnostic and Statistical Manual of Mental Disorders, 4th edition and 106
      nondemented control subjects who visited our clinic with a main complaint of
      headache or dizziness. We examined retrospectively the effects of RASB on
      adipocytokines and cognitive decline in patients with AD who were divided into
      three groups: hypertension treated with RASB (HT-RASB; n = 17), hypertension
      treated with other antihypertensive drugs (HT-other; n = 34), and no hypertension
      (non-HT; n = 27). RESULTS: The HT-RASB group had a significantly higher serum
      leptin level and a relatively larger visceral fat area than the other groups,
      because of the bias toward patients with MetS in this group. The HT-RASB group
      also had a significantly lower immunoreactive insulin level, a relatively low
      homeostasis model assessment as an index of insulin resistance, and a relatively
      high serum adiponectin level among the three groups. Cognitive decline, estimated
      on the basis of the mean annual decline using the Hasegawa Dementia Scale score
      was significantly low in the HT-RASB group. CONCLUSION: Treatment with RASB might
      modulate serum adipocytokines and glucose homeostasis, potentially slowing
      cognitive decline in patients with AD.

PMID- 23142435
TI  - Thrombosis incidence in unilateral vs. simultaneous bilateral total knee
      arthroplasty with compression device prophylaxis.
AB  - This study compares the incidence of venous thromboembolic event (VTE) in 55
      patients (110 knees) undergoing simultaneous bilateral TKA with 287 patients (287
      knees) undergoing unilateral TKA using a mobile compression device as monotherapy
      prophylaxis in both groups. All patients were clinically evaluated 3months after
      surgery with symptomatic confirmed VTE as an endpoint. Deep venous thrombosis
      (DVT) was documented by duplex ultrasound and pulmonary embolism (PE) was
      documented by spiral CT. The simultaneous bilateral TKA group had 6 VTEs (10.9%)
      with 2 PEs (3.6%). The unilateral TKA group had 9 VTEs (3.1%), and 0 PE. Patients
      undergoing simultaneous bilateral TKA yielded more than twice the rate of VTE
      compared with patients undergoing unilateral TKA using a mobile compression
      device as sole thromboprophylactic modality.

PMID- 23142436
TI  - Factors influencing patients' willingness to pay for new technologies in hip and
      knee implants.
AB  - Rising implant prices and evolving technologies are important factors
      contributing to the increased cost of arthroplasty. Assessing how patients value
      arthroplasty, new technologies, and their perceived outcomes is critical in
      planning cost-effective care, as well as evaluating new-technologies. One hundred
      one patients undergoing arthroplasty took part in the survey. We captured
      demographics, spending practices, knowledge of implants, patient willingness to
      pay for implants, and preferences related to implant attributes. When patients
      were asked if they would be satisfied with "standard of care" prosthesis, 80%
      replied "no". When asked if they would pay for a higher than "standard of care"
      prosthesis, 86% replied "yes". The study demonstrated that patients, regardless
      of their socio-economic status, are not satisfied with standard of care implants
      when newer technologies are available, and they may be willing to share in the
      cost of their prosthesis. Patients also prefer the option to choose what they
      perceive to be a higher quality or innovative implant even if the "out of pocket"
      cost is higher.

PMID- 23142437
TI  - Stable fixation but unpredictable bone remodelling around the Lord stem: minimum
      23-year follow-up of 66 total hip arthroplasties.
AB  - Early designs of uncemented hip implants turned out to be failures mainly because
      the prerequisites for durable implant fixation were unknown. One exception was
      the chrome-cobalt stem of the Madreporic Lord prosthesis. We prospectively
      studied this prosthetic design in 107 hips that underwent surgery in 1979-1986.
      At the last follow-up, five stems and 54 cups had been revised, corresponding to
      stem and cup survival rates of 92%+/-3% and 45%+/-5% at 26years. In all, 66 hips
      with remaining Lord stems were available for clinical follow-up 26years (24-29)
      after the index operation. The mean total Harris hip and pain scores were 81 (SD
      14) and 41 (SD 5).

PMID- 23142438
TI  - Implant and limb alignment outcomes for conventional and navigated
      unicompartmental knee arthroplasty.
AB  - Accurate implant positioning and restoration of lower limb alignment are major
      requirements for successful long-term results in unicompartmental knee
      arthroplasty (UKA). Alignment accuracy was compared between navigated-UKA (nUKA)
      and conventional-UKA (cUKA) groups using a retrospective matched case-control
      study (n=129, 58 nUKA, 71 cUKA). Mechanical axis (MA), hip-knee-ankle angle (HKA
      degrees ), coronal implant alignment, and tibial implant posterior slope were
      measured. No statistically significant difference was observed when comparing MA,
      HKA degrees  or coronal implant alignment (p>0.05). Statistical significance was
      seen with tibial component posterior slope (p=0.04, nUKA 4.2 degrees , cUKA 2.9
      degrees ); and between intra-operative navigationally determined HKA degrees  and
      post-operative whole-leg standing (WLS) film HKA degrees . Navigation does not
      significantly improve UKA alignment compared to conventional methods. Further
      studies are needed to justify the use of this technology in UKA.

PMID- 23142439
TI  - Effect of zoledronic acid on reducing femoral bone mineral density loss following
      total hip arthroplasty: preliminary results of a prospective randomized trial.
AB  - This randomized trial evaluated the effect of zoledronic acid on femoral bone
      mineral density (BMD) following primary total hip arthroplasty. Bone mineral
      density was compared for up to 2years in 27 patients receiving 5mg zoledronic
      acid intravenous infusion and in 24 patients receiving placebo at 2weeks and
      1year after surgery. Zoledronic acid prevented loss of bone mineral density at
      1year (+13.8% vs +1.4%, P=.0065) and 2years (+14.3% vs -4.0%, P<.0001) in Gruen
      zone 1, at 1year (-8.4% vs -25.4%, P<.0001) and 2years (-9.6% vs -27.3%, P<.0001)
      in Gruen zone 7, at 6weeks, 6months, and 1 or 2years in Gruen zones 4 and 6. For
      all Gruen zones, prevention of BMD loss by ZOL was significant at 6weeks,
      6months, 1year (+0.80% vs -6.03%, P<.0001) and 2years (-0.16% vs -7.13%,
      P<.0001).

PMID- 23142440
TI  - Leg-length discrepancy after revision hip arthroplasty: are modular stems
      superior?
AB  - We retrospectively reviewed data for 79 consecutive patients who underwent
      revision hip arthroplasty using cementless femoral stems at our center between
      September 2008 and November 2010. Two cohorts were included, one using MP
      (modular) femoral stems and the other using Wagner (monoblock) femoral stems. We
      assessed leg-length discrepancy (LLD) before and after revision and compared the
      occurrence of leg-length inequality between the 2 cohorts. We found that the
      incidence of LLD was high in revision hip arthroplasty and that leg shortening
      was more common than lengthening. Both acetabular and femoral sides contributed
      to postoperative LLD. Appropriate placement of the femoral components was most
      critical in adjusting LLD. We also found that compared with monoblock stems,
      modular stems made adjustment of postoperative leg length easier.

PMID- 23142441
TI  - Comparing the analgesia effects of single-injection and continuous femoral nerve
      blocks with patient controlled analgesia after total knee arthroplasty.
AB  - We compared the analgesic effects of single-injection or continuous femoral nerve
      block (FNB) with intravenous patient controlled analgesia (PCA) opioids. Two
      hundred patients undergoing knee arthroplasty were randomized to one of the three
      regimens. Significant knee pain on movement at postoperative 24h was reduced with
      single-injection (OR 0.30; 95% CI 0.12 to 0.74; P=0.009) or continuous (OR 0.21;
      95% CI 0.08 to 0.51; P=0.001) FNB, compared with PCA. Allocation to FNBs also
      resulted in significantly less opioid consumption, fewer episodes of nausea and
      vomiting, and achieved knee flexion 90 degrees  earlier than allocation to PCA.
      Compared to single-injection FNB, patients with continuous FNB had lower pain
      scores on movement at 24h (mean difference -0.57; 95% CI -1.14 to -0.01;
      P=0.045), consumed less opioid, and had fewer incidences of nausea and vomiting.
      The analgesic efficacy of single-injection and continuous FNBs was superior to
      PCA in the immediate postoperative period; with continuous FNB providing better
      analgesia than single-injection FNB.

PMID- 23142442
TI  - Clinical and kinematic outcomes of a rotating platform posterior stabilized total
      knee system.
AB  - Early post-operative clinical outcomes were analyzed for subjects having a
      rotating platform (RP) posterior stabilized (PS) total knee arthroplasty (TKA); a
      subset of which underwent in vivo kinematics and produced kinematic results that
      compare well with subjects in previous fluoroscopic studies that were deemed
      excellent in nature. In total, 153 subjects (180 knees) were enrolled in the
      prospective clinical study. TKAs were performed by three surgeons at three North
      American centers. Ten subjects were randomly chosen and evaluated under
      fluoroscopic surveillance. Average active flexion increased from 113.3 (SD=16.6)
      degrees before surgery to 118.3 (SD=9.9) degrees 12-months post-operatively.
      American Knee Society (AKS) function score increased from an average of 57.6
      (SD=18.8) points pre-operatively to 85.3 (SD=16.6) points 12-months post
      operatively. For the kinematic subset, post-operative weight-bearing flexion was
      115.9 (SD=8.4),while subjects achieved an average posterior femoral rollback of
      their lateral condyle of -5.4mm. The average femorotibial axial rotation from
      full extension to maximum weight-bearing flexion was 3.9 degrees (SD=3.9).
      Certain kinematic parameters were deemed statistically significant when
      determining early post-operative clinical success.

PMID- 23142443
TI  - The Cardiff Arthroplasty Satisfaction Index (CASI). A simple tool for the
      assessment of outcome following knee arthroplasty.
AB  - Our aim was to develop a patient reported outcome measure of satisfaction
      following total knee arthroplasty (TKA) and assess its correlation with Oxford
      knee score (OKS), Quality of life (EQ5D) and Visual analogue scale for pain
      (VAS). 172 patients with minimum 5year follow up post primary total knee
      arthroplasty completed CASI, OKS, EQ5D and VAS for pain. Receiver-operator curve
      analysis was performed to identify an OKS threshold of poor satisfaction defined
      by CASI rarely/never. The CASI showed positive correlation with the OKS, VAS for
      pain, and EQ5D, (Spearman's rho); 0.779; 0.711; 0.629. A threshold of 20 for the
      Oxford Knee score had 85% specificity and 85% sensitivity for poor satisfaction
      on CASI. The CASI is a useful measure of patient satisfaction following TKA.

PMID- 23142444
TI  - In-hospital surgical site infections after primary hip and knee arthroplasty-
      incidence and risk factors.
AB  - Data of hospitalizations for THA or TKA were analyzed for each year between 1998
      and 2007 from the National Inpatient Sample. Demographics, comorbidities,
      incidence of morbidity and mortality, length of hospital stay (LOS), and overall
      cost were compared for infected and non-infected patients. Perioperative SSI
      rates were 0.36% for THA and 0.31% for TKA (412,356 and 784,335 patient entries,
      respectively). Patients with SSI had a significantly higher overall comorbidity
      burden, higher perioperative mortality rates, longer length of stay, and higher
      complication rates. Average cost of in-hospital care was double for SSI versus
      non-SSI patients. Independent risk factors for perioperative SSI included male
      gender, minority race, a diagnosis for cancer, liver disease, coagulopathies,
      fluid and electrolyte disorders, congestive heart failure, and pulmonary
      circulatory disease. Data relied on coded information and could not differentiate
      between superficial or deep infection, or capture patients readmitted for SSI,
      and therefore may have underestimated the true incidence of SSI.

PMID- 23142445
TI  - WITHDRAWN: Inpatient Mortality After Primary Total Hip Arthroplasty: Analysis
      From The National Inpatient Sample Database.
AB  - This article has been withdrawn at the request of the author(s). 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- 23142446
TI  - Mortality, cost, and health outcomes of total knee arthroplasty in Medicare
      patients.
AB  - There are little data that quantify the long term costs, mortality, and
      downstream disease after Total Knee Arthroplasty (TKA). The purpose of this study
      is to compare differences in cost and health outcomes between Medicare patients
      with OA who undergo TKA and those who avoid the procedure. The Medicare 5% sample
      was used to identify patients diagnosed with OA during 1997-2009. All OA patients
      were separated into non-arthroplasty and arthroplasty groups. Differences in
      costs, mortality, and new disease diagnoses were adjusted using logistic
      regression for age, sex, race, buy-in status, region, and Charlson score. The 7
      year cumulative average Medicare payments for all treatments were $63,940 for the
      non-TKA group and $83,783 for the TKA group. The risk adjusted mortality hazard
      ratio (HR) of the TKA group ranged from 0.48 to 0.54 through seven years (all
      P<0.001). The risk of heart failure in the TKA group was 40.9% at 7years
      (HR=0.93, P<0.001). The results demonstrate the patients in the TKA cohort as
      having a lower probability of heart failure and mortality, at a total incremental
      cost of $19,843.

PMID- 23142447
TI  - Incidence, predictors, and effects of residual flexion contracture on clinical
      outcomes of total knee arthroplasty.
AB  - Patients who present with large flexion contracture (FC) but have well maintained
      maximum flexion tend to have a flexion-extension gap mismatch, which can cause
      residual FC or flexion instability after TKA. We routinely use posterior
      stabilized implants, perform soft tissue balancing and additional distal femur
      resection, and determine the polyethylene insert thickness based on flexion
      extension gap difference to avoid postoperative FC and flexion instability. We
      retrospectively reviewed 911 TKAs performed with this protocol to determine the
      incidence, predictors and effects of postoperative FC on clinical outcomes. Knees
      with postoperative FC >=10 degrees  were identified, and their clinical outcomes
      were compared with knees without FC. The average follow-up period was 35months
      (range, 24-72months). Eighteen (2.0%) of the 911 knees presented with
      postoperative FC. The occurrence of postoperative FC was associated with
      preoperative FC and anterior knee pain, but not with a flexion-extension gap
      mismatch. A mild to moderate postoperative FC does not increase pain, but may be
      detrimental to quality of life.

PMID- 23142448
TI  - Radiological evaluation of acetabular erosion after antibiotic-impregnated
      polymethylmethacrylate spacer (Spacer-G).
AB  - Different types of hip spacers have been described (hand-made, custom-molded or
      prefabricated) for treatment of a chronic hip infection. A potential disadvantage
      of monoblock prefabricated spacer is that it may cause acetabular bone loss. This
      study assesses the radiological acetabular erosion using an antibiotic
      impregnated pre-fabricated polymethylmethacrylate Spacer-G. We retrospectively
      reviewed the radiographs of thirty five patients who were managed with Spacer-G
      to treat chronic hip infection. No acetabular erosion were observed in thirty two
      patients with a mean time from the first to second stage and from the first to
      the last radiograph of 5.09 and 3.77 months respectively. In three patients the
      time between the radiographs was more than one year and the second stage was not
      performed; two developed a protrusion acetabuli whereas the other one a
      destruction of the acetabular roof. Using a Spacer-G in chronic hip infection
      treatment for less than one year is not associated with radiological acetabular
      erosion if the patient is maintained at partial weight bearing.

PMID- 23142449
TI  - A randomized trial of ceramic-on-ceramic bearing versus ceramic-on-crossfire
      polyethylene bearing in total hip arthroplasty: five-year outcomes.
AB  - This study determined how ceramic-on-ceramic bearing THA affected joint-specific
      pain, function and stiffness in the first five postoperative years compared with
      ceramic-on-highly-crosslinked-polyethylene bearing THA. Subjects less than 61
      years of age were randomized to ceramic-on-ceramic (CERAMIC) [n = 48] or ceramic
      on-highly-crosslinked-polyethylene (POLYETHYLENE) [n = 44] bearing THA. Subjects
      were assessed using the Western Ontario McMaster Osteoarthritis Index (WOMAC) and
      the RAND 12-Item Health Survey (RAND-12) preoperatively, and at one and five
      years postoperatively. 92 subjects(50 (54%) males; average age = 52 (SD 6.6)
      years) were enrolled. 78 (85%) subjects returned five years postoperatively. All
      subjects reported improvements at one and five years in all measured indices with
      no group differences detected. Seven (8%) subjects experienced postoperative THA
      complications, none related to bearing surfaces; two subjects (POLYETHYLENE)
      required revision for instability. Both bearing surfaces provided excellent short
      term results in younger subjects.

PMID- 23142450
TI  - Safety and efficacy of multimodal thromboprophylaxis following total knee
      arthroplasty: a comparative study of preferential aspirin vs. routine coumadin
      chemoprophylaxis.
AB  - Multimodal thromboprophylaxis encompasses preoperative VTE risk stratification,
      regional anesthesia, mechanical prophylaxis, and early mobilization. We
      determined if aspirin can be safely used for adjuvant chemoprophylaxis in
      patients who have a low thromboembolic risk. 1016 consecutive patients undergoing
      TKA received multimodal thromboprophylaxis. Aspirin was used in 67% of patients
      and Coumadin 33% (high risk patients, or who were on Coumadin before surgery).
      This study group was compared to 1001 consecutive patients who received
      multimodal thromboprophylaxis and routine Coumadin chemoprophylaxis. There was no
      significant difference in rates of VTE, PE, bleeding, complications, readmission
      and 90-day mortality between the two groups. There was a significantly higher
      rate of wound related complications in the control group (p=0.03). Multimodal
      thromboprophylaxis with aspirin given to the majority of patients at a low VTE
      risk is safe and effective in patients undergoing primary TKA.

PMID- 23142451
TI  - Body mass index as predictor of health-related quality-of-life changes after
      total hip arthroplasty: a cross-over study.
AB  - The objective of this study was to examine the contribution of patient weight and
      other preoperative variables to improvements in the general physical health of
      patients undergoing total hip arthroplasty (THA). Data were prospectively
      collected on 63 THA patients (28 males and 35 females). The primary outcome
      measure was the improvement in general health (Short Form-12 Health Survey
      questionnaire) at three months post-THA. Patients with body mass index >28kg/m(2)
      showed greater improvements in function and in the physical component of general
      health after THA. Stepwise regression analyses revealed that the BMI and WOMAC
      general index were independent and significant predictors of physical function
      and together explained 34.2% of the variance in physical function scores. These
      findings suggest that the body mass index before surgery and improvements in hip
      function are relevant contributors to post-THA improvements in general health.

PMID- 23142452
TI  - Risk factors for early mortality following modern total hip arthroplasty.
AB  - The aim of this study was to evaluate the incidence of early mortality and
      identify risk factors for early death following modern uncemented THA. Between
      2000 and 2006, we identified patients who died within 90days of THA.
      Demographics, comorbidities, laboratory studies, and complications were analyzed
      as risk factors for mortality. 38 of 8261 patients undergoing THA (0.46%) died
      within 90days postoperatively. Of these, 26% were due to myocardial infarction.
      Multivariate analysis revealed Charlson index >3, peripheral vascular disease,
      elevated postoperative glucose, and abnormal postoperative cardiac studies as
      independent predictors of early mortality following THA. Caution should be taken
      in patients with increased comorbidities, PVD, perioperative hyperglycemia, and
      impaired renal function in order to reduce mortality following THA.

PMID- 23142453
TI  - Total knee arthroplasty in patients with excessive external tibial torsion >45
      degrees  and patella instability--surgical technique and follow up.
AB  - Patients presenting with advanced knee osteoarthritis (OA), excessive external
      tibial torsion (EETT) and chronic patella subluxation pose significant surgical
      challenges. A combination of TKA, tibial derotation osteotomy, and tibial
      tuberosity transfer was performed in ten patients (twelve knees) with OA
      secondary to EETT and patellar instability. Six weeks of non weight-bearing and
      flexion limited to 45 degrees  was mandated after surgery. The mean follow-up and
      patient age was 81months (range, 14 to 159) and 56years (range, 49 to 62). The
      mean pre-operative external tibial torsion was 62 degrees , with an average
      rotational correction of 30 degrees . Significant improvement was found in the
      Knee Society Score, SF-12 and all WOMAC questionnaire score subscales (p<0.0001);
      5 patients had complications, but no loosening or nonunion was seen.

PMID- 23142454
TI  - The increased utilization of operating room time in patients with increased BMI
      during primary total hip arthroplasty.
AB  - While obesity is associated with increased need for total hip arthroplasty (THA),
      the relationship between body mass index (BMI) and operative duration is unknown.
      We reviewed a series of 425 primary THAs implanted by one surgeon from 2004 to
      2010. Patients were grouped by BMI based on the World Health Organization's
      categorization. Intraoperative time measurements (Total Room Time, Anesthesia
      Induction Time, Surgery Time) were compared across groups. Mean times were
      analyzed using a one-way ANOVA with post-hoc least squares difference test.
      Operating time increased progressively with increasing BMI category. Significant
      differences were found between normal weight patients and all 3 obesity groups in
      total room and surgery times. Obese patients spend more time in the OR during
      THA, reflecting the burden obesity poses to surgeons and hospitals.

PMID- 23142455
TI  - High initial stability in porous titanium acetabular cups: a biomechanical study.
AB  - Initial stability with limited micromotion in uncemented total hip arthroplasty
      acetabular components is essential for bony attachment and long-term
      biomechanical fixation. This study compared porous titanium fixation surfaces to
      clinically established, plasma-sprayed designs in terms of interface stability
      and required seating force. Porous plasma-sprayed modular and metal-on-metal
      (MOM) cups were compared to a modular, porous titanium designs. Cups were
      implanted into polyurethane blocks with1-mm interference fit and subsequently
      edge loaded to failure. Porous titanium cups exhibited 23% to 65% improvement in
      initial stability when compared to plasma-sprayed cup designs (P=.01): a
      clinically significant increase, based on experience and prior literature. The
      results of this study indicate increased interface stability in porous titanium
      coated cups without significantly increasing the necessary force and energy
      required for full seating.

PMID- 23142456
TI  - Variations in surgeons' recovery expectations for patients undergoing total joint
      arthroplasty: a survey of the AAHKS membership.
AB  - Recovery expectations (RE) after total hip and knee arthroplasty (THA-TKA)
      influence outcomes. We surveyed AAHKS members to determine variation in surgeon
      RE. Four vignettes depicting patients with high and low expectations after THA
      and TKA were distributed with a validated RE survey. Responses were analyzed for
      clinically significant differences between surgeons and within surgeons. Of 1049
      surgeons surveyed, 358 (34%) responded. There was a clinically significant
      difference in 85% (high-THA), 46% (low-THA), 74% (high-TKA), and 57% (low-TKA) of
      pairs. Disagreement was significantly greater in high expectation vignettes.
      Individual surgeons distinguished between high and low expectation patients in
      76% (THA) and 72% (TKA) of cases. There was no association between surgeon RE and
      practice demographics. Wide variations in RE were observed, especially among high
      expectation patients.

PMID- 23142457
TI  - Immunoreactivity between venoms and commercial antiserums in four Chinese snakes
      and venom identification by species-specific antibody.
AB  - We studied the immunoreactivity between venoms and commercial antiserums in four
      Chinese venomous snakes, Bungarus multicinctus, Naja atra, Deinagkistrodon acutus
      and Gloydius brevicaudus. Venoms from the four snakes shared common antigenic
      components, and most venom components expressed antigenicity in the immunological
      reaction between venoms and antiserums. Antiserums cross-reacted with
      heterologous venoms. Homologous venom and antiserum expressed the highest
      reaction activity in all cross-reactions. Species-specific antibodies (SSAbs)
      were obtained from four antiserums by immunoaffinity chromatography: the whole
      antiserum against each species was gradually passed through a medium system
      coated with heterologous venoms, and the cross-reacting components in antiserum
      were immunoabsorbed by the common antigens in heterologous venoms; the unbound
      components (i.e., SSAbs) were collected, and passed through Hitrap G protein
      column and concentrated. The SSAbs were found to have high specificity by western
      blot and enzyme-linked immunosorbent assay (ELISA). A 6-well ELISA strip coated
      with SSAbs was used to assign a venom sample and blood and urine samples from the
      envenomed rats to a given snake species. Our detections could differentiate
      positive and negative samples, and identify venoms of a snake species in about 35
      min. The ELISA strips developed in this study are clinically useful in rapid and
      reliable identification of venoms from the above four snake species.

PMID- 23142458
TI  - Detection of neutralizing antibodies to erythropoietin by inhibition of rHuEPO
      stimulated EGR1 gene expression in the UT-7/EPO cell line.
AB  - Recombinant erythropoietin (rHuEPO) is used extensively to treat anaemia
      associated with chronic kidney disease. However, the development of neutralizing
      antibodies (NAbs) to rHuEPO can result in the development of antibody-mediated
      pure red cell aplasia (PRCA). The detection of NAb in patient sera by in vitro
      bioassay relies on the inhibition of a cellular response to rHuEPO. Current
      bioassays for rHuEPO measure proliferation in responsive cell lines such as the
      erythroleukaemic cell lines, UT-7 and UT-7/EPO, the latter sensitized to EPO.
      Using these cell lines, we show the dose-responsive induction of both PIM1 and
      EGR1 gene expression in UT-7 cells and of EGR1 in UT-7/EPO cells. The expression
      of EGR1 in UT-7/EPO cells in response to rHuEPO was comparable to the
      proliferative response measured by (3)H-thymidine incorporation and could be
      inhibited by serum from a patient with NAb-mediated PRCA in a dilution-dependent
      manner. Bioassays based on the induction of endogenous gene expression are
      comparable to current bioassays but are considerably quicker given that
      incubation time is decreased from 2-3 days to 50 min. Measurement of EGR1 gene
      expression in response to rHuEPO in UT-7/EPO cells offers a rapid, non
      radioactive and automatable alternative to current assays for the detection of
      rHuEPO NAbs.

PMID- 23142459
TI  - Purification of antibodies to O antigen of Salmonella Typhimurium from human
      serum by affinity chromatography.
AB  - Nontyphoidal Salmonellae (NTS) are a common cause of bacteraemia in children and
      HIV-infected adults in Sub-Saharan Africa. We have previously shown that
      antibodies play a key role in both bactericidal and cellular mechanisms of
      immunity to NTS, but found that high concentrations of antibody to Salmonella
      Typhimurium O antigen (OAg) in the serum of some HIV-infected African adults is
      associated with impaired killing of NTS. To further investigate the function of
      antibodies to the OAg of NTS, we developed a method to purify these antibodies
      from human serum by affinity chromatography. Purified Salmonella Typhimurium OAg
      was activated with adipic acid dihydrazide (ADH) via two different chemistries
      before linking to N-hydroxysuccinamide-Sepharose resin: one ADH molecule was
      introduced per OAg chain on its terminal 3-deoxy-D-manno-octulosonic acid sugar
      (OAg-ADH), or multiple ADH molecules were attached along the OAg chain after
      oxidation with sodium periodate (OAgoxADH). Both resulting columns worked well
      when tested with commercial polyclonal anti-O:4,5 antibodies from rabbit serum.
      Over 90% of the applied antibodies bound to the resin and 89% of these antibodies
      were then eluted as detected by ELISA. OAg-ADH was preferred as the method for
      OAg derivatisation as it does not modify the saccharide chain and can be applied
      to OAg from different bacteria. Both columns were able to bind OAg-specific
      antibodies in human serum, but antibody recovery was initially low. Different
      elution buffers were tested and different amounts of OAg-ADH were linked to the
      resin to improve the yield. Optimal recovery (51%) was obtained by loading 1mg of
      activated OAg per ml of resin and eluting with 0.1M glycine, 0.1M NaCl pH2.4. The
      column matrix could be regenerated following elution with no detectable loss in
      performance for over ten uses. This method offers the potential to purify
      antibodies to Salmonella OAg from polyclonal serum following vaccination or
      natural exposure to Salmonella and so investigate the functionality and diversity
      of the antibody response to OAg.

PMID- 23142460
TI  - Comparison of flow cytometry and indirect immunofluorescence assay in the
      diagnosis and cure criterion after therapy of American tegumentary leishmaniasis
      by anti-live Leishmania (Viannia) braziliensis immunoglobulin G.
AB  - The aim of this study was to compare the techniques of indirect
      immunofluorescence assay (IFA) and flow cytometry to clinical and laboratorial
      evaluation of patients before and after clinical cure and to evaluate the
      applicability of flow cytometry in post-therapeutic monitoring of patients with
      American tegumentary leishmaniasis (ATL). Sera from 14 patients before treatment
      (BT), 13 patients 1 year after treatment (AT), 10 patients 2 and 5 years AT were
      evaluated. The results from flow cytometry were expressed as levels of IgG
      reactivity, based on the percentage of positive fluorescent parasites (PPFP). The
      1:256 sample dilution allowed us to differentiate individuals BT and AT.
      Comparative analysis of IFA and flow cytometry by ROC (receiver operating
      characteristic curve) showed, respectively, AUC (area under curve)=0.8 (95%
      CI=0.64-0.89) and AUC=0.90 (95% CI=0.75-0.95), demonstrating that the flow
      cytometry had equivalent accuracy. Our data demonstrated that 20% was the best
      cut-off point identified by the ROC curve for the flow cytometry assay. This test
      showed a sensitivity of 86% and specificity of 77% while the IFA had a
      sensitivity of 78% and specificity of 85%. The after-treatment screening, through
      comparative analysis of the technique performance indexes, 1, 2 and 5 years AT,
      showed an equal performance of the flow cytometry compared with the IFA. However,
      flow cytometry shows to be a better diagnostic alternative when applied to the
      study of ATL in the cure criterion. The information obtained in this work opens
      perspectives to monitor cure after treatment of ATL.

PMID- 23142461
TI  - Generation of tissue-specific H-2Kd transgenic mice for the study of K(d)
      restricted malaria epitope-specific CD8+ T-cell responses in vivo.
AB  - CD8(+) T cells are critical for the control of various intracellular infections
      and cancers. To date, however, effective T cell-based vaccines remain elusive,
      due, in part, to the lack of in vivo models that facilitate the dissection of
      antigen-specific CD8(+) T-cell responses primed by different antigen-presenting
      cells (APCs). In this study, we generated four lines of H-2K(d) transgenic (K(d)
      Tg) mice that differed in their expression of H-2K(d): dendritic cells (DCs) only
      (CD11c-K(d)), macrophages only (huCD68-K(d)), hepatocytes only (Alb-K(d)), or all
      nucleated cells (major histocompatibility complex-I-K(d)). Immunization of each
      of these K(d) Tg mouse strains with a synthetic peptide or a recombinant
      adenovirus expressing a well-known immunodominant, H-2K(d)-restricted CD8(+) T
      cell epitope, SYVPSAEQI, which was derived from the circumsporozoite protein of
      Plasmodium yoelii, promoted distinct SYVPSAEQI-specific CD8(+) T-cell responses.
      The route of immunization also greatly influenced the magnitude of the epitope
      specific CD8(+) T-cell response. These tissue-specific K(d) Tg mice may be
      valuable tools for determining the mode of induction of CD8(+) T-cell responses
      by different APCs in vivo and for characterizing the CD8(+) T-cell responses
      promoted in response to various microbial infections and/or different types of
      vaccines.

PMID- 23142462
TI  - A novel assay to quantitate MASP-2/ficolin-3 complexes in serum.
AB  - Ficolin-1, -2 and -3 are recognition molecules in the lectin complement pathway
      and form complexes with serine proteases named MASP-1, -2 and -3 and two
      nonenzymatic proteins. MASP-2 is the main initiator of lectin pathway activation,
      while ficolin-3 is the most abundant ficolin molecule in the circulation. The
      significance of lectin pathway complexes in the circulation is unknown. Thus, we
      established an assay for the measurement of circulating MASP-2/ficolin-3
      complexes. A quantitative sandwich ELISA was developed for the measurement of the
      MASP-2/ficolin-3 complexes in serum based on monoclonal antibodies against MASP-2
      for coating and anti-ficolin-3 for detection. In addition, we assessed the serum
      concentrations of ficolin-3 and MASP-2 and the extent of ficolin-3 mediated C4
      deposition on acetylated BSA in samples from 97 healthy donors. The median
      concentration of MASP-2/ficolin-3 complexes was found to be 119.7 AU/ml (range:
      2.9-615.5 AU/ml). Significant correlations were found between the level of MASP
      2/ficolin-3 complexes and the concentration of ficolin-3 (Spearman r=0.2532,
      p=0.0124), and MASP-2 (Spearman r=0.4505, p<0.0001), as well as the degree of C4
      deposition (Spearman r=0.671, p<0.0001). When ficolin-3 deficient (homozygous for
      the rs28357092 polymorphism) and MASP-2 deficient (homozygous for the rs72550870
      polymorphism) sera were incubated together, complex formation was induced between
      MASP-2 and ficolin-3. The complex formation disappeared in the presence of EDTA.
      An assay allowing quantitative measurement exclusively of MASP-2/ficolin-3
      complexes in serum is described. This method may add further insight into the
      pathophysiology of disorders associated with the deficiency or abnormal
      activities of MASP-2 and ficolin-3.

PMID- 23142463
TI  - Preparation and characterization of monoclonal antibody specific for copper
      chelate complex.
AB  - Monoclonal antibody (MAb) against chelated Cu(2+) was developed. The conjugate
      employed as immunogens in BALB/c mice to raise antibodies was synthesized using
      Cu(2+) coupling to keyhole limpet hemocyanin (KLH) via a bifunctional chelator (2
      (4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic
      acid, p-SCN-Bn-DOTA). One of the hybridomas secreting antibody that bound tightly
      to Cu(2+)-ethylenediamine tetraacetic acid (EDTA) complex but not to metal-free
      EDTA was isolated from the fusion between murine splenocytes and SP2/0 myeloma
      cells. The performance of a competitive enzyme-linked immunosorbent assay (ELISA)
      was assessed for its sensitivity to changes in pH and ionic strength. The cross
      reactivities (CR) with other metals were below 1%, except for Hg(2+) with a CR of
      7.19 %. The IC(50) value achieved for copper was 0.89 MUg/mL, showing a detection
      range of 0.25-8.13 MUg/mL and the lowest detection limit of 0.032 MUg/mL. The
      concentration of Cu(2+) in environmental water and serum samples obtained by
      ELISA correlated well with Atomic Absorption Spectrometry (AAS), and the mean
      recovery was 93.7%. These results indicated that ELISA could be a convenient
      analytical tool for monitoring copper in drinking water and human serum.

PMID- 23142464
TI  - Fluorochemicals used in food packaging inhibit male sex hormone synthesis.
AB  - Polyfluoroalkyl phosphate surfactants (PAPS) are widely used in food contact
      materials (FCMs) of paper and board and have recently been detected in 57% of
      investigated materials. Human exposure occurs as PAPS have been measured in
      blood; however knowledge is lacking on the toxicology of PAPS. The aim of this
      study was to elucidate the effects of six fluorochemicals on sex hormone
      synthesis and androgen receptor (AR) activation in vitro. Four PAPS and two
      metabolites, perfluorooctanoic acid (PFOA) and 8:2 fluorotelomer alcohol (8:2
      FTOH) were tested. Hormone profiles, including eight steroid hormones, generally
      showed that 8:2 diPAPS, 8:2 monoPAPS and 8:2 FTOH led to decreases in androgens
      (testosterone, dehydroepiandrosterone, and androstenedione) in the H295R
      steroidogenesis assay. Decreases were observed for progesterone and 17-OH
      progesterone as well. These observations indicated that a step prior to
      progestagen and androgen synthesis had been affected. Gene expression analysis of
      StAR, Bzrp, CYP11A, CYP17, CYP21 and CYP19 mRNA showed a decrease in Bzrp mRNA
      levels for 8:2 monoPAPS and 8:2 FTOH indicating interference with cholesterol
      transport to the inner mitochondria. Cortisol, estrone and 17beta-estradiol
      levels were in several cases increased with exposure. In accordance with these
      data CYP19 gene expression increased with 8:2 diPAPS, 8:2 monoPAPS and 8:2 FTOH
      exposures indicating that this is a contributing factor to the decreased androgen
      and the increased estrogen levels. Overall, these results demonstrate that
      fluorochemicals present in food packaging materials and their metabolites can
      affect steroidogenesis through decreased Bzrp and increased CYP19 gene expression
      leading to lower androgen and higher estrogen levels.

PMID- 23142465
TI  - Cell-specific oxidative stress and cytotoxicity after wildfire coarse particulate
      matter instillation into mouse lung.
AB  - Our previous work has shown that coarse particulate matter (PM(10-2.5)) from
      wildfire smoke is more toxic to lung macrophages on an equal dose (by mass) basis
      than coarse PM isolated from normal ambient air, as evidenced by decreased
      numbers of macrophages in lung lavage fluid 6 and 24hours after PM instillation
      into mouse lungs in vivo and by cytotoxicity to a macrophage cell line observed
      directly in vitro. We hypothesized that pulmonary macrophages from mice instilled
      with wildfire coarse PM would undergo more cytotoxicity than macrophages from
      controls, and that there would be an increase in oxidative stress in their lungs.
      Cytotoxicity was quantified as decreased viable macrophages and increased
      percentages of dead macrophages in the bronchoalveolar lavage fluid (BALF) of
      mice instilled with wildfire coarse PM. At 1hour after PM instillation, we
      observed both decreased numbers of viable macrophages and increased dead
      macrophage percentages as compared to controls. An increase in free isoprostanes,
      an indicator of oxidative stress, from control values of 28.1+/-3.2pg/mL to
      83.9+/-12.2pg/mL was observed a half-hour after PM instillation. By 1hour after
      PM instillation, isoprostane values had returned to 30.4+/-7.6pg/mL, not
      significantly different from control concentrations. Lung sections from mice
      instilled with wildfire coarse PM showed rapid Clara cell responses, with
      decreased intracellular staining for the Clara cell secretory protein CCSP 1hour
      after wildfire PM instillation. In conclusion, very rapid cytotoxicity occurs in
      pulmonary macrophages and oxidative stress responses are seen 0.5-1hour after
      wildfire coarse PM instillation. These results define early cellular and
      biochemical events occurring in vivo and support the hypothesis that oxidative
      stress-mediated macrophage toxicity plays a key role in the initial response of
      the mouse lung to wildfire PM exposure.

PMID- 23142467
TI  - Maternal in utero exposure to the endocrine disruptor di-(2-ethylhexyl) phthalate
      affects the blood pressure of adult male offspring.
AB  - Di-(2-ethylhexyl) phthalate (DEHP) is used industrially to add flexibility to
      polyvinyl chloride (PVC) polymers and is ubiquitously found in the environment,
      with evidence of prenatal, perinatal and early infant exposure in humans. In
      utero exposure to DEHP decreases circulating testosterone levels in the adult
      rat. In addition, DEHP reduces the expression of the angiotensin II receptors in
      the adrenal gland, resulting in decreased circulating aldosterone levels. The
      latter may have important effects on water and electrolyte balance as well as
      systemic arterial blood pressure. Therefore, we determined the effects of in
      utero exposure to DEHP on systemic arterial blood pressure in the young (2month
      old) and older (6.5month-old) adult rats. Sprague-Dawley pregnant dams were
      exposed from gestational day 14 until birth to 300mg DEHP/kg/day. Blood pressure,
      heart rate, and activity data were collected using an intra-aortal transmitter in
      the male offspring at postnatal day (PND) 60 and PND200. A low (0.01%) and high
      salt (8%) diet was used to challenge the animals at PND200. In utero exposure to
      DEHP resulted in reduced activity at PND60. At PND200, systolic and diastolic
      systemic arterial pressures as well as activity were reduced in response to DEHP
      exposure. This is the first evidence showing that in utero exposure to DEHP has
      cardiovascular and behavioral effects in the adult male offspring.

PMID- 23142466
TI  - Toxicodynamics of rigid polystyrene microparticles on pulmonary gas exchange in
      mice: implications for microemboli-based drug delivery systems.
AB  - The toxicodynamic relationship between the number and size of pulmonary
      microemboli resulting from uniformly sized, rigid polystyrene microparticles
      (MPs) administered intravenously and their potential effects on pulmonary gas
      exchange were investigated. CD-1 male mice (6-8 weeks) were intravenously
      administered 10, 25 and 45 MUm diameter MPs. Oxygen hemoglobin saturation in the
      blood (SpO(2)) was measured non-invasively using a pulse oximeter while varying
      inhaled oxygen concentration (F(I)O(2)). The resulting data were fit to a
      physiologically based non-linear mathematical model that estimates 2 parameters:
      ventilation-perfusion ratio (V(A)/Q) and shunt (percentage of deoxygenated blood
      returning to systemic circulation). The number of MPs administered prior to a
      statistically significant reduction in normalized V(A)/Q was dependent on
      particle size. MP doses that resulted in a significant reduction in normalized
      V(A)/Q one day post-treatment were 4000, 40,000 and 550,000 MPs/g for 45, 25 and
      10 MUm MPs, respectively. The model estimated V(A)/Q and shunt returned to
      baseline levels 7 days post-treatment. Measuring SpO(2) alone was not sufficient
      to observe changes in gas exchange; however, when combined with model-derived
      V(A)/Q and shunt early reversible toxicity from pulmonary microemboli was
      detected suggesting that the model and physical measurements are both required
      for assessing toxicity. Moreover, it appears that the MP load required to alter
      gas exchange in a mouse prior to lethality is significantly higher than the
      anticipated required MP dose for effective drug delivery. Overall, the current
      results indicate that the microemboli-based approach for targeted pulmonary drug
      delivery is potentially safe and should be further explored.

PMID- 23142468
TI  - Equine cytochrome P450 2B6--genomic identification, expression and functional
      characterization with ketamine.
AB  - Ketamine is an anesthetic and analgesic regularly used in veterinary patients. As
      ketamine is almost always administered in combination with other drugs,
      interactions between ketamine and other drugs bear the risk of either adverse
      effects or diminished efficacy. Since cytochrome P450 enzymes (CYPs) play a
      pivotal role in the phase I metabolism of the majority of all marketed drugs,
      drug-drug interactions often occur at the active site of these enzymes. CYPs have
      been thoroughly examined in humans and laboratory animals, but little is known
      about equine CYPs. The characterization of equine CYPs is essential for a better
      understanding of drug metabolism in horses. We report annotation, cloning and
      heterologous expression of the equine CYP2B6 in V79 Chinese hamster fibroblasts.
      After computational annotation of all CYP2B genes, the coding sequence (CDS) of
      equine CYP2B6 was amplified by RT-PCR from horse liver total RNA and revealed an
      amino acid sequence identity of 77% and a similarity of 93.7% to its human
      ortholog. A non-synonymous variant c.226G>A in exon 2 of the equine CYP2B6 was
      detected in 97 horses. The mutant A-allele showed an allele frequency of 82%. Two
      further variants in exon 3 were detected in one and two horses of this group,
      respectively. Transfected V79 cells were incubated with racemic ketamine and
      norketamine as probe substrates to determine metabolic activity. The recombinant
      equine CYP2B6 N-demethylated ketamine to norketamine and produced metabolites of
      norketamine, such as hydroxylated norketamines and 5,6-dehydronorketamine. V(max)
      for S-/and R-norketamine formation was 0.49 and 0.45nmol/h/mg cellular protein
      and K(m) was 3.41 and 2.66MUM, respectively. The N-demethylation of S-/R-ketamine
      was inhibited concentration-dependently with clopidogrel showing an IC(50) of
      5.63 and 6.26MUM, respectively. The functional importance of the recorded genetic
      variants remains to be explored. Equine CYP2B6 was determined to be a CYP enzyme
      involved in ketamine and norketamine metabolism, thus confirming results from
      inhibition studies with horse liver microsomes. Clopidogrel seems to be a
      feasible inhibitor for equine CYP2B6. The specificity still needs to be
      established with other single equine CYPs. Heterologous expression of single
      equine CYP enzymes opens new possibilities to substantially improve the
      understanding of drug metabolism and drug interactions in horses.

PMID- 23142469
TI  - Development of doxorubicin-induced chronic cardiotoxicity in the B6C3F1 mouse
      model.
AB  - Serum levels of cardiac troponins serve as biomarkers of myocardial injury.
      However, troponins are released into the serum only after damage to cardiac
      tissue has occurred. Here, we report development of a mouse model of doxorubicin
      (DOX)-induced chronic cardiotoxicity to aid in the identification of predictive
      biomarkers of early events of cardiac tissue injury. Male B6C3F(1) mice were
      administered intravenous DOX at 3mg/kg body weight, or an equivalent volume of
      saline, once a week for 4, 6, 8, 10, 12, and 14weeks, resulting in cumulative DOX
      doses of 12, 18, 24, 30, 36, and 42mg/kg, respectively. Mice were sacrificed a
      week following the last dose. A significant reduction in body weight gain was
      observed in mice following exposure to a weekly DOX dose for 1week and longer
      compared to saline-treated controls. DOX treatment also resulted in declines in
      red blood cell count, hemoglobin level, and hematocrit compared to saline-treated
      controls after the 2nd weekly dose until the 8th and 9th doses, followed by a
      modest recovery. All DOX-treated mice had significant elevations in cardiac
      troponin T concentrations in plasma compared to saline-treated controls,
      indicating cardiac tissue injury. Also, a dose-related increase in the severity
      of cardiac lesions was seen in mice exposed to 24mg/kg DOX and higher cumulative
      doses. Mice treated with cumulative DOX doses of 30mg/kg and higher showed a
      significant decline in heart rate, suggesting drug-induced cardiac dysfunction.
      Altogether, these findings demonstrate the development of DOX-induced chronic
      cardiotoxicity in B6C3F(1) mice.

PMID- 23142470
TI  - Zinc oxide nanoparticles and monocytes: impact of size, charge and solubility on
      activation status.
AB  - Zinc oxide (ZnO) particle induced cytotoxicity was dependent on size, charge and
      solubility, factors which at sublethal concentrations may influence the
      activation of the human monocytic cell line THP1. ZnO nanoparticles (NP; average
      diameter 70nm) were more toxic than the bulk form (<44MUm mesh) and a positive
      charge enhanced cytotoxicity of the NP despite their relatively high dissolution.
      A positive charge of the particles has been shown in other studies to have an
      influence on cell viability. Centrifugal filtration using a cut off of 5kDa and
      Zn element analysis by atomic absorption spectroscopy confirmed that exposure of
      the ZnO particles and NP to 10% foetal bovine serum resulted in a strong
      association of the Zn(2+) ion with protein. This association with protein may
      influence interaction of the ZnO particles and NP with THP1 cells. After 24h
      exposure to the ZnO particles and NP at sublethal concentrations there was little
      effect on immunological markers of inflammation such as HLA DR and CD14, although
      they may induce a modest increase in the adhesion molecule CD11b. The cytokine
      TNFalpha is normally associated with proinflammatory immune responses but was not
      induced by the ZnO particles and NP. There was also no effect on LPS stimulated
      TNFalpha production. These results suggest that ZnO particles and NP do not have
      a classical proinflammatory effect on THP1 cells.

PMID- 23142471
TI  - CYP2E1-dependent elevation of serum cholesterol, triglycerides, and hepatic bile
      acids by isoniazid.
AB  - Isoniazid is the first-line medication in the prevention and treatment of
      tuberculosis. Isoniazid is known to have a biphasic effect on the inhibition
      induction of CYP2E1 and is also considered to be involved in isoniazid-induced
      hepatotoxicity. However, the full extent and mechanism of involvement of CYP2E1
      in isoniazid-induced hepatotoxicity remain to be thoroughly investigated. In the
      current study, isoniazid was administered to wild-type and Cyp2e1-null mice to
      investigate the potential toxicity of isoniazid in vivo. The results revealed
      that isoniazid caused no hepatotoxicity in wild-type and Cyp2e1-null mice, but
      produced elevated serum cholesterol and triglycerides, and hepatic bile acids in
      wild-type mice, as well as decreased abundance of free fatty acids in wild-type
      mice and not in Cyp2e1-null mice. Metabolomic analysis demonstrated that
      production of isoniazid metabolites was elevated in wild-type mice along with a
      higher abundance of bile acids, bile acid metabolites, carnitine and carnitine
      derivatives; these were not observed in Cyp2e1-null mice. In addition, the
      enzymes responsible for bile acid synthesis were decreased and proteins involved
      in bile acid transport were significantly increased in wild-type mice. Lastly,
      treatment of targeted isoniazid metabolites to wild-type mice led to similar
      changes in cholesterol, triglycerides and free fatty acids. These findings
      suggest that while CYP2E1 is not involved in isoniazid-induced hepatotoxicity,
      while an isoniazid metabolite might play a role in isoniazid-induced cholestasis
      through enhancement of bile acid accumulation and mitochondria beta-oxidation.

PMID- 23142472
TI  - Gestational exposure to diethylstilbestrol alters cardiac structure/function,
      protein expression and DNA methylation in adult male mice progeny.
AB  - Pregnant women, and thus their fetuses, are exposed to many endocrine disruptor
      compounds (EDCs). Fetal cardiomyocytes express sex hormone receptors making them
      potentially susceptible to re-programming by estrogenizing EDCs.
      Diethylstilbestrol (DES) is a proto-typical, non-steroidal estrogen. We
      hypothesized that changes in adult cardiac structure/function after gestational
      exposure to the test compound DES would be a proof in principle for the
      possibility of estrogenizing environmental EDCs to also alter the fetal heart.
      Vehicle (peanut oil) or DES (0.1, 1.0 and 10.0MUg/kg/da.) was orally delivered to
      pregnant C57bl/6n dams on gestation days 11.5-14.5. At 3months, male progeny were
      left sedentary or were swim trained for 4weeks. Echocardiography of isoflurane
      anesthetized mice revealed similar cardiac structure/function in all sedentary
      mice, but evidence of systolic dysfunction and increased diastolic relaxation
      after swim training at higher DES doses. The calcium homeostasis proteins,
      SERCA2a, phospholamban, phospho-serine 16 phospholamban and calsequestrin 2, are
      important for cardiac contraction and relaxation. Immunoblot analyses of
      ventricle homogenates showed increased expression of SERCA2a and calsequestrin 2
      in DES mice and greater molecular remodeling of these proteins and phospho-serine
      16 phospholamban in swim trained DES mice. DES increased cardiac DNA
      methyltransferase 3a expression and DNA methylation in the CpG island within the
      calsequestrin 2 promoter in heart. Thus, gestational DES epigenetically altered
      ventricular DNA, altered cardiac function and expression, and reduced the ability
      of adult progeny to cardiac remodel when physically challenged. We conclude that
      gestational exposure to estrogenizing EDCs may impact cardiac structure/function
      in adult males.

PMID- 23142473
TI  - Superparamagnetic iron oxide polyacrylic acid coated gamma-Fe2O3 nanoparticles do
      not affect kidney function but cause acute effect on the cardiovascular function
      in healthy mice.
AB  - This study describes the distribution of intravenously injected polyacrylic acid
      (PAA) coated gamma-Fe(2)O(3) NPs (10 mg kg(-1)) at the organ, cellular and
      subcellular levels in healthy BALB/cJ mice and in parallel addresses the effects
      of NP injection on kidney function, blood pressure and vascular contractility.
      Magnetic resonance imaging (MRI) and transmission electron microscopy (TEM)
      showed accumulation of NPs in the liver within 1h after intravenous infusion,
      accommodated by intracellular uptake in endothelial and Kupffer cells with
      subsequent intracellular uptake in renal cells, particularly the cytoplasm of the
      proximal tubule, in podocytes and mesangial cells. The renofunctional effects of
      NPs were evaluated by arterial acid-base status and measurements of glomerular
      filtration rate (GFR) after instrumentation with chronically indwelling
      catheters. Arterial pH was 7.46+/-0.02 and 7.41+/-0.02 in mice 0.5 h after
      injections of saline or NP, and did not change over the next 12 h. In addition,
      the injections of NP did not affect arterial PCO(2) or [HCO(3)(-)] either. Twenty
      four and 96 h after NP injections, the GFR averaged 0.35+/-0.04 and 0.35+/-0.01
      ml min(-1) g(-1), respectively, values which were statistically comparable with
      controls (0.29+/-0.02 and 0.33+/-0.1 ml(-1) min(-1) 25 g(-1)). Mean arterial
      blood pressure (MAP) decreased 12-24 h after NP injections (111.1+/-11.5 vs
      123.0+/-6.1 min(-1)) associated with a decreased contractility of small
      mesenteric arteries revealed by myography to characterize endothelial function.
      In conclusion, our study demonstrates that accumulation of superparamagnetic iron
      oxide nanoparticles does not affect kidney function in healthy mice but
      temporarily decreases blood pressure.

PMID- 23142474
TI  - Oxidative stress induced by palytoxin in human keratinocytes is mediated by a H+
      dependent mitochondrial pathway.
AB  - In the last decades, massive blooms of palytoxin (PLTX)-producing Ostreopsis cf.
      ovata have been observed along Mediterranean coasts, usually associated to human
      respiratory and cutaneous problems. At the molecular level, PLTX induces a
      massive intracellular Na(+) influx due to the transformation of Na(+)/K(+) ATPase
      in a cationic channel. Recently, we have demonstrated that Na(+) overload is the
      crucial step in mediating overproduction of reactive oxygen species (ROS) and
      cell death in human HaCaT keratinocytes, tentatively explaining PLTX-induced skin
      irritant effects. In the present study the molecular mechanisms of ROS production
      induced by PLTX-mediated Na(+) intracellular overload have been investigated. In
      HaCaT cells, PLTX exposure caused accumulation of superoxide anion, but not of
      nitric oxide or peroxynitrite/hydroxyl radicals. Even if RT-PCR and western blot
      analysis revealed an early NOX-2 and iNOS gene and protein over-expressions,
      their active involvement seemed to be only partial since selective inhibitors did
      not completely reduce O(2)(-) production. A significant role of other enzymes
      (COX-1, COX-2, XO) was not evidenced. Nigericin, that counteracts Na(+)-mediated
      H(+)-imbalance, dissipating DeltapH across mitochondrial inner membrane, and the
      uncouplers DNP significantly reduced O(2)(-) production. These inhibitions were
      synergistic when co-exposed with complex-I inhibitor rotenone. These results
      suggest a novel mechanism of O(2)(-) production induced by PLTX-mediated ionic
      imbalance. Indeed, the H(+) intracellular overload that follows PLTX-induced
      intracellular Na(+) accumulation, could enhance DeltapH across mitochondrial
      inner membrane, that seems to be the driving force for O(2)(-) production by
      reversing mitochondrial electron transport.

PMID- 23142475
TI  - Pharmacokinetic drivers of toxicity for basic molecules: strategy to lower pKa
      results in decreased tissue exposure and toxicity for a small molecule Met
      inhibitor.
AB  - Several toxicities are clearly driven by free drug concentrations in plasma, such
      as toxicities related to on-target exaggerated pharmacology or off-target
      pharmacological activity associated with receptors, enzymes or ion channels.
      However, there are examples in which organ toxicities appear to correlate better
      with total drug concentrations in the target tissues, rather than with free drug
      concentrations in plasma. Here we present a case study in which a small molecule
      Met inhibitor, GEN-203, with significant liver and bone marrow toxicity in
      preclinical species was modified with the intention of increasing the safety
      margin. GEN-203 is a lipophilic weak base as demonstrated by its physicochemical
      and structural properties: high LogD (distribution coefficient) (4.3) and high
      measured pKa (7.45) due to the basic amine (N-ethyl-3-fluoro-4-aminopiperidine).
      The physicochemical properties of GEN-203 were hypothesized to drive the high
      distribution of this compound to tissues as evidenced by a moderately-high volume
      of distribution (Vd>3l/kg) in mouse and subsequent toxicities of the compound.
      Specifically, the basicity of GEN-203 was decreased through addition of a second
      fluorine in the 3-position of the aminopiperidine to yield GEN-890 (N-ethyl-3,3
      difluoro-4-aminopiperidine), which decreased the volume of distribution of the
      compound in mouse (Vd=1.0l/kg), decreased its tissue drug concentrations and led
      to decreased toxicity in mice. This strategy suggests that when toxicity is
      driven by tissue drug concentrations, optimization of the physicochemical
      parameters that drive tissue distribution can result in decreased drug
      concentrations in tissues, resulting in lower toxicity and improved safety
      margins.

PMID- 23142476
TI  - Molecular mechanisms in spindle positioning: structures and new concepts.
AB  - Coordination of cell cleavage with respect to cell geometry, cell polarity and
      neighboring tissues is critical for tissue maintenance, malignant transformation
      and metastasis. The position of the mitotic spindle within the cell determines
      where cell cleavage occurs. Spindle positioning is often mediated through capture
      of astral microtubules by motor proteins at the cell cortex. Recently, the core
      dynein anchor complex has been structurally resolved. Junctional complexes were
      shown to provide additional capture sites for astral microtubules in
      proliferating tissues. Finally, latest studies show that signals from centrosomes
      control spindle positioning and propose novel concepts for generation of
      centrosome identity.

PMID- 23142477
TI  - Recent advances in X-chromosome inactivation research.
AB  - X-chromosome inactivation is the mechanism ensuring dosage compensation in
      mammals. It is regulated by the X-inactivation center (Xic), which harbors the
      main regulator of XCI, the long non-coding RNA Xist. In the past two years
      significant advances have been made in our understanding of how Xist is regulated
      by its neighbors in the Xic and in a developmental context. New technologies,
      such as chromosome conformation capture and live cell imaging, have helped us
      understand the topological organization of the Xic and the dynamics of this locus
      during differentiation. Here, we will describe some of the most recent findings
      made in X-inactivation research with a special focus on the regulation of Xist
      and the spatial organization of the Xic.

PMID- 23142478
TI  - Effects of Arg-Gly-Asp-modified elastin-like polypeptide on pseudoislet formation
      via up-regulation of cell adhesion molecules and extracellular matrix proteins.
AB  - Extracellular matrix (ECM) plays an important role in controlling the beta-cell
      morphology, survival and insulin secretary functions. An RGD-modified elastin
      like polypeptide (RGD-ELP), TGPG[VGRGD(VGVPG)(6)](20)WPC, has been reported
      previously as a bioactive matrix. In this study, to investigate whether RGD-ELP
      affects beta-cell growth characteristics and insulin secretion, beta-TC6 cells
      were cultured on the RGD-ELP coatings prepared via thermally induced phase
      transition. On RGD-ELP, beta-TC6 cells clustered into an islet-like architecture
      with high cell viability. Throughout 7days' culture, the proliferation rate of
      the cells within a pseudoislet was similar to that of monolayer culture. Under
      high glucose (25mM), beta-TC6 pseudoislets showed up-regulated insulin gene
      expression and exhibited glucose-stimulated insulin secretion. Importantly, the
      mRNA and protein abundances of cell adhesion molecules (CAM) E-cadherin and
      connexin-36 were much higher in pseudoislets than in monolayer cells. The siRNA
      mediated inhibition of E-cadherin or connexin-36 expression severely limited
      pseudoislet formation. In addition, the mRNA levels of collagen types I and IV,
      fibronectin and laminin were significantly elevated in pseudoislets. The results
      suggest that RGD-ELP promotes pseudoislet formation via up-regulation of the CAM
      and ECM components. The functional roles of RGD-ELP are discussed in respect of
      its molecular composition.

PMID- 23142479
TI  - A temperature-cured dissolvable gelatin microsphere-based cell carrier for
      chondrocyte delivery in a hydrogel scaffolding system.
AB  - In this study, a novel therapeutic cell delivery methodology in the form of
      hydrogel encapsulating cell-laden microspheres was developed and investigated. As
      a model cell for cartilage tissue engineering, chondrocytes were successfully
      encapsulated in gelatin-based microspheres (mostly of diameter 50-100 MUm,
      centred at 75-100 MUm) with high cell viability during the formation of
      microspheres via a water-in-oil single emulsion process under a low temperature
      without any chemical treatment. These cell-laden microspheres were then
      encapsulated in alginate-based hydrogel constructs. By elevating the temperature
      to 37 degrees C, the cell-laden microspheres were completely dissolved within 2
      days, resulting in the same number of same-sized spherical cavities in hydrogel
      bulk, along with which the encapsulated cells were released from the microspheres
      and suspended inside the cavities to be cultivated for further development. In
      this cell delivery system, the microspheres played a dual role as both removable
      cell vehicles and porogens for creation of the intra-hydrogel cavities, in which
      the delivered cells were provided with both free living spaces and a better
      permeable environment. This temperature-cured dissolvable gelatin microsphere
      based cell carrier (tDGMC) associating with cell-laden hydrogel scaffold was
      attempted and evaluated through WST-1, quantitative polymerase chain reaction,
      biochemical assays and various immunohistochemistry and histology stains. The
      results indicate that tDGMC technology can facilitate the delivery of
      chondrocytes, as a non-anchorage-dependent therapeutic cell, with significantly
      greater efficiency.

PMID- 23142480
TI  - Monolithic and assembled polymer-ceramic composites for bone regeneration.
AB  - The rationale for the use of polymer-ceramic composites for bone regeneration
      stems from the natural composition of bone, with collagen type I and biological
      apatite as the main organic and inorganic constituents, respectively. In the
      present study composite materials of PolyActiveTM (PA), a poly(ethylene oxide
      terephthalate)/poly(butylene terephtalate) co-polymer, and hydroxyapatite (HA) at
      a weight ratio of 85:15 were prepared by rapid prototyping (RP) using two routes.
      In the first approach pre-extruded composite filaments of PA-HA were processed
      using three-dimensional fibre deposition (3DF) (conventional composite
      scaffolds). In the second approach PA scaffolds were fabricated using 3DF and
      combined with HA pillars produced inside stereolithographic moulds that fitted
      inside the pores of the PA three-dimensional structure (assembled composite
      scaffolds). Analysis of calcium and phosphate release in a simulated
      physiological solution, not containing calcium or phosphate, revealed
      significantly higher values for the HA pillars compared with other scaffolds.
      Release in simulated body fluid saturated with respect to HA did not show
      significant differences among the different scaffolds. Human mesenchymal stromal
      cells were cultured on polymer (3DF), conventional composite (3DF-HA) and
      assembled composite (HA assembled in 3DF) scaffolds and assessed for morphology,
      metabolic activity, DNA amount and gene expression of osteogenic markers using
      real time quantitative polymerase chain reaction (PCR). Scanning electron
      microscopy images showed that the cells attached to and infiltrated all the
      scaffolds. Assembled composites had a higher metabolic activity compared with 3DF
      HA scaffolds while no significant differences were observed in DNA amounts. Gene
      expression of osteopontin in the assembled composite was significantly higher
      compared with the conventional composites. The strategy of composite fabrication
      by assembly appears to be a promising alternative to the conventional composite
      fabrication route for scaffolds for bone regeneration.

PMID- 23142481
TI  - Facets of protein assembly on nanostructured titanium oxide surfaces.
AB  - One key for the successful integration of implants into the human body is the
      control of protein adsorption by adjusting the surface properties at different
      length scales. This is particularly important for titanium oxide, one of the most
      common biomedical interfaces. As for titania (TiO(2)) the interface is largely
      defined by its crystal surface structure, it is crucial to understand how the
      surface crystallinity affects the structure, properties and function of protein
      layers mediating subsequent biological reactions. For rutile TiO(2) we
      demonstrate that the conformation and relative amount of human plasma fibrinogen
      (HPF) and the structure of adsorbed HPF layers depend on the crystal surface
      nanostructure by employing thermally etched multi-faceted TiO(2) surfaces.
      Thermal etching of polycrystalline TiO(2) facilitates a nanoscale crystal
      faceting and, thus, the creation of different surface nanostructures on a single
      specimen surface. Atomic force microscopy shows that HPF arranges into networks
      and thin globular layers on flat and irregular crystal grain surfaces,
      respectively. On a third, faceted category we observed an alternating
      conformation of HPF on neighboring facets. The bulk grain orientation obtained
      from electron backscatter diffraction and thermodynamic mechanisms of surface
      reconstruction during thermal etching suggest that the grain and facet surface
      specific arrangement and relative amount of adsorbed proteins depend on the
      associated free crystal surface energy. The implications for potentially
      favorable TiO(2) crystal facets regarding the inflammatory response and
      hemostasis are discussed with a view to the advanced surface design of future
      implants.

PMID- 23142482
TI  - Development of a micro-imaging probe for functional brain imaging.
AB  - Multicellular neuronal activities should be investigated to reveal the dynamics
      of the neuronal circuit. Optical recording from neuronal populations is suitable
      for recording multicellular activities. We fabricated the prototype of the micro
      imaging probe in combination with a gradient index lens and image fiber. This
      probe has a smaller diameter than traditional probes. We found an optimal optical
      configuration for maximizing the efficiency of the imaging probe. Using this
      optical configuration with the prototype of the imaging probe, the fluorescence
      images were captured from neurons expressing green fluorescent protein in a
      cerebellar block preparation, and the calcium-dependent images were sampled in a
      mouse brain slice preparation. Our optical system would facilitate the in vivo
      imaging studies with less invasive manners using thinner optic fiber than
      previously made.

PMID- 23142483
TI  - Genetic deletion of the EGFR ligand epigen does not affect mouse embryonic
      development and tissue homeostasis.
AB  - The epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor with
      manifold functions during development, tissue homeostasis and disease. EGFR
      activation, the formation of homodimers or heterodimers (with the related ERBB2-4
      receptors) and downstream signaling is initiated by the binding of a family of
      structurally related growth factors, the EGFR ligands. Genetic deletion
      experiments clarified the biological function of all family members except for
      the last characterized ligand, epigen. We employed gene targeting in mouse
      embryonic stem cells to generate mice lacking epigen expression. Loss of epigen
      did not affect mouse development, fertility, or organ physiology. Quantitative RT
      PCR analysis revealed increased expression of betacellulin and EGF in a few
      organs of epigen-deficient mice, suggesting a functional compensation by these
      ligands. In conclusion, we completed the genetic analysis of EGFR ligands and
      show that epigen has non-essential functions or functions that can be compensated
      by other EGFR ligands during growth and tissue homeostasis.

PMID- 23142484
TI  - Estrogen defines the dynamics and destination of transactivated EGF receptor in
      breast cancer cells: role of S1P3 receptor and Cdc42.
AB  - Sphingosine-1-phosphate (S1P) receptors mediate transactivation of epidermal
      growth factor receptor (EGFR) by estrogen (E2). Here we report that the amount of
      intracellular EGFR remains elevated after stimulation of MCF-7 cells with E2 and
      S1P, although membrane-localized EGFR and S1P3 receptors are quickly
      internalized. Co-localization of internalized EGFR and LAMP-2 was lower in cells
      treated with E2/S1P, suggesting that endosomal EGFR might be directed for
      recycling instead of degradation. In addition, we found that E2/S1P activated
      Cdc42 and that knockdown of Cdc42 restores fast EGFR degradation after E2/S1P
      stimulation. Inhibition of S1P3 receptors prevented E2-induced activation of
      Cdc42, supporting the important role of the S1P receptor in E2 signaling. This is
      a novel mechanism further defining the effect of E2/S1P on the EGFR
      transactivation in breast cancer cells.

PMID- 23142485
TI  - The influence of the sounds of crying baby and the sounds of violence on
      haemodynamic parameters and autonomic status in young, healthy adults.
AB  - INTRODUCTION: There is evidence that various stimuli affect the balance in the
      autonomic nervous system (ANS) and the functioning of cardiovascular system.
      OBJECTIVE: The aim of the study was to assess whether the sounds of crying baby
      and the sounds of violence affected haemodynamic parameters and ANS in young,
      healthy adults and to measure differences in these reactions between the genders
      and these 2 stimuli. METHODS: Haemodynamic parameters (measured non-invasively by
      the NEXFIN device), heart rate and blood pressure variability (HRV and BPV,
      respectively) and baroreflex sensitivity (BRS) were analyzed in 65 adults (21
      women, mean age: 23years) during a 15-minute rest followed by the emission of two
      5-minute acoustic stimuli: sounds of crying baby and sounds of violence emitted
      randomly and separated by a 4-minute pause. RESULTS: Resting systolic blood
      pressure was lower, whereas indices of HRV (RMSSD, NN50, pNN50, high frequency
      component of HRV - HRV HF) and BPV (high frequency component - BPV HF) as well as
      BRS were higher in women as compared to men. During the emission of the sounds of
      crying baby, a decrease in diastolic blood pressure (DBP), systemic vascular
      resistance index, HRV HF and BPV LF (low frequency component of BPV) and an
      increase in stroke volume index were observed in the whole examined group,
      whereas during the emission of the sounds of violence subjects presented a
      decrease in DBP, mean blood pressure, HRV HF and BPV LF. The reaction to the
      sounds of crying baby (expressed as a decrease in HRV HF) was greater in women as
      compared to men (-0.28+/-0.49 versus -0.04+/-0.38ms(2), p=0.04). The comparison
      of the reaction between 2 stimuli revealed no differences. CONCLUSIONS: The
      stronger decrease in parasympathetic drive in women exposed to the sounds of
      crying baby may be related to a particular role of this stimulus, which signals
      the baby's distress and compels the caregivers to react.

PMID- 23142486
TI  - Recent structural and mechanistic insights into post-translational enzymatic
      glycosylation.
AB  - Enzymatic glycosylation of proteins, a post-transitional modification of great
      significance, is carried out by diverse glycosyltransferases (GTs) that harness
      activated sugar donors, typically nucleotide or lipid-phosphate linked species.
      Recent work has seen a major increase in the study of the 3D structure and
      reaction mechanism of these enzymes. Key advances include the dissection of the
      classical O-glycosylating and N-glycosylating apparatus, revealing unusual folds
      and hitherto unconsidered chemical mechanisms for acceptor activation. There has
      been considerable success in the application of kinetic isotope effects and
      quantum simulations to address the controversial issue of the reaction mechanism
      of retaining GTs. New roles for old modifications, exemplified by potential
      epigenetic roles for glycosylation, have been discovered and there has also been
      a plethora of studies into important mammalian glycosylations that play key roles
      in cellular biology, opening up new targets for chemical intervention approaches.

PMID- 23142487
TI  - Edible bird's nests--how do the red ones get red?
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Red edible bird's nests are regarded as of higher
      beneficial value for health and hence fetch a higher price than the white ones.
      Their red colour remains a myth. AIM OF THE STUDY: To determine if white edible
      bird's nests can turn red by vapours generated from sodium nitrite in acidic
      conditions and by vapours from 'bird soil'. MATERIALS AND METHODS: White edible
      bird's nests were exposed to vapours from sodium nitrite dissolved in 2% HCl or
      from 'bird soil' in hot and humid conditions. CONCLUSIONS: Vapours from sodium
      nitrite dissolved in 2% HCl or from 'bird soil' containing guano droppings from
      swiftlet houses were able to turn white edible bird's nests red. The reddening
      agent in 'bird soil' was water-soluble and heat-stable. The red colour of edible
      bird's nests is likely caused by the environmental factors in cave interiors and
      swiftlet houses.

PMID- 23142488
TI  - Antihypertensive effects of extract from Picrasma quassiodes (D. Don) Benn. in
      spontaneously hypertensive rats.
AB  - ETHNOPHARMACOLOGICA RELEVANCE: Picrasma quassiodes (D. Don) Benn. (PQB) is a
      widely used herbal medicine used for gastroenteritis, snakebite, infection and
      hypertension in China. The aim of the study was to investigate the possible
      antihypertensive mechanisms on spontaneously hypertensive rats (SHR) of the
      extract from Picrasma quassiodes (D. Don) Benn. MATERIALS AND METHODS: In the in
      vivo study, extract from Picrasma quassiodes (D. Don) Benn. at the dose of 50,
      100, 200mg/kg and captopril (12.5mg/kg) were administrated to different group of
      SHR rats by gavage for six consecutive weeks after the blood pressures were
      firstly measured. At the end of the study, rats serum nitric oxide (NO) was
      measured by the nitrate reductase method; superoxide dismutase (SOD) and
      malondialdehyde (MDA) activities were measured by the colorimetric method; the
      expression of aorta endothelial nitric oxide synthase (eNOS) was measured by
      immunohistochemical analysis. RESULTS: The results showed that the oral
      administration of PQB could lower the systolic blood pressure (SBP) of SHR rats.
      In addition, the serum level of NO in SHR treated with PQB (100 and 200mg/kg) was
      increased dramatically (P<0.05, P<0.01), but administration with captopril had no
      significant effect. The expression of aorta eNOS was markedly increased when
      treated with PQB. The serum SOD levels were increased with treatment of PQB (100
      and 200mg/kg; P<0.05, P<0.01). All the effects of these parameters were
      comparable to that of the SHR control group. CONCLUSIONS: Our results disclosed
      that PQB is effective to lower blood pressure of SHR, its antihypertensive effect
      is probably associated with lowering oxidative stress by reducing SOD activity,
      preserving endothelial function and increasing the expression of eNOS to regulate
      NO and directly relax artery.

PMID- 23142489
TI  - Phenotypic variation caused by variation in the relative copy number of pDU1
      based plasmids expressing the GAF domain of Pkn41 or Pkn42 in Anabaena sp. PCC
      7120.
AB  - The cyanobacterium Anabaena (Nostoc) sp. PCC 7120 is a model for cyanobacterial
      cell differentiation studies. pDU1, an endogenous plasmid in Nostoc sp. PCC 7524,
      is used as the only cyanobacterial replicon for Anabaena (Nostoc) studies.
      However, the relative copy numbers of pDU1-based plasmids in Anabaena (Nostoc)
      sp. PCC 7120 are not well studied. We found that the relative plasmid copy number
      of one such vector, pRL25T, varied widely, especially when the vector carried a
      recombinant insert, under different conditions, ranging from 0.53 to 1812 per
      chromosome in different recombinant strains tested, either in independent clones
      of the same strain or in the same clone under different growth conditions. The
      phenotypes caused by pRL25T-driven expression of green fluorescent protein or the
      GAF domain of Pkn41 or Pkn42 varied depending on the independent clones analyzed.
      This phenotypic variation correlated with the relative plasmid copy number
      present in cells.

PMID- 23142490
TI  - Rapid and accurate identification of isolates of Candida species by melting peak
      and melting curve analysis of the internally transcribed spacer region 2 fragment
      (ITS2-MCA).
AB  - Rapid identification of clinically important yeasts can facilitate the initiation
      of anti-fungal therapy, since susceptibility is largely species-dependent. We
      evaluated melting peak and melting curve analysis of the internally transcribed
      spacer region 2 fragment (ITS2-MCA) as an identification tool for distinguishing
      between 16 Candida spp., i.e. Candida albicans, Candida bracarensis, Candida
      dubliniensis, Candida famata, Candida glabrata, Candida guilliermondii, Candida
      inconspicua, Candida kefyr, Candida krusei, Candida lipolytica, Candida
      lusitaniae, Candida nivariensis, Candida norvegensis, Candida parapsilosis,
      Candida tropicalis and Candida sojae, and Saccharomyces cerevisiae and one
      species pair, i.e. Candida metapsilosis/Candida orthopsilosis. Starting from a
      cultured isolate, ITS2-MCA led to differentiation of these species within 6 h.
      According to our findings, ITS2-MCA offers a simple, rapid and cost-effective
      method for identification of cultured isolates of the clinically most relevant
      and prevalent Candida species. Further studies will be necessary to evaluate how
      it performs on mixed samples and clinical samples.

PMID- 23142491
TI  - Physico-chemical factors affect chloramphenicol efflux and EmhABC efflux pump
      expression in Pseudomonas fluorescens cLP6a.
AB  - Protein synthesis inhibitors such as chloramphenicol and tetracycline may be
      inducers of efflux pumps such as MexY in Pseudomonas aeruginosa, complicating
      their use for the treatment of bacterial infections. We previously determined
      that chloramphenicol, a substrate of the EmhABC efflux pump in Pseudomonas
      fluorescens cLP6a, did not induce emhABC expression. In this study, we determined
      the effect of physico-chemical factors on chloramphenicol efflux by EmhABC, and
      the expression of emhABC. Efflux assays measuring accumulation of (14)C
      chloramphenicol in cell pellets showed that chloramphenicol efflux is dependent
      on growth temperature, pH and concentration of Mg(2+). These physico-chemical
      factors modulated the efflux of chloramphenicol by 26 to >50%. All conditions
      tested that decreased the efflux of chloramphenicol unexpectedly induced
      transcription of emhABC efflux genes. EmhABC activity also effectively suppressed
      the deleterious effect of chloramphenicol on the cell membrane of strain cLP6a,
      which may explain why chloramphenicol is not an inducer of emhABC. Our results
      suggest that the detrimental effect of an antibiotic on cell membrane integrity
      and fatty acid composition may be the signal that induces emhABC expression, and
      that inducers of other bacterial efflux pumps may include environmental factors
      rather than their substrates per se.

PMID- 23142492
TI  - High-energy pulse-electron-beam-induced molecular and cellular damage in
      Saccharomyces cerevisiae.
AB  - The high-energy pulse electron beam (HEPE) is a new method for mutation breeding.
      Previously, we demonstrated that HEPE radiation improved thermotolerance and
      ethanol production of Saccharomyces cerevisiae. To investigate the influence of
      HEPE on yeast molecular and cellular damage, cells were separately treated with
      HEPE radiation at different doses (0, 200, 400, 600, 800, 1000, 1200 and 1400
      Gy). Based on results obtained, protein leakage and diffusion of intracellular
      nucleotide and propidium iodide (PI) uptake assays showed that HEPE clearly
      enhanced the cell membrane permeability of yeast depending on the dose of
      exposure. Yeast cells treated with HEPE radiation had significantly elevated
      levels of DNA instability, as detected by the chromosome spreading assay. These
      results correlated well with the measurement of increased levels of chromosomal
      aberrations and apoptosis. Intracellular reactive oxygen species (ROS) and
      caspase 3 activity were also measured in HEPE-applied yeast cells. Caspase 3
      appeared to be involved in HEPE-induced apoptosis. Use of dihydroethidium
      staining and confocal laser scanning microscopy (CLSM) showed increased levels of
      intracellular ROS as a consequence of augmented pulsing. Moreover, yeast cells
      retained some photoreactivation capacity when the dose of HEPE exposure was less
      than 600 Gy. Thereafter, the level of damage was too serious to repair. Thus,
      photoreactivation had a repair effect upon HEPE radiation-induced damage. The
      results of our studies provide a possible explanation for the molecular and
      cellular effects of HEPE radiation upon S. cerevisiae.

PMID- 23142493
TI  - Dopaminergic dysfunction in abstinent dexamphetamine users: results from a
      pharmacological fMRI study using a reward anticipation task and a methylphenidate
      challenge.
AB  - BACKGROUND: Dopamine (DA) is involved in systems governing motor actions,
      motivational processes and cognitive functions. Preclinical studies have shown
      that even relatively low doses of d-amphetamine (dAMPH) (equivalent to doses used
      in clinical Practice) can lead to DA neurotoxicity in rodents and non-human
      primates (Ricaurte et al., 2005). METHODS: Therefore, we investigated the DAergic
      function in eight male recreational users of dAMPH and eight male healthy
      controls using functional magnetic resonance imaging (fMRI). We compared brain
      activation between both groups during a monetary incentive delay task (Knutson et
      al., 2001) with and without an oral methylphenidate (MPH) challenge. All subjects
      were abstinent for at least 2 weeks during the baseline scan. The second scan was
      performed on the same day 1.5 h after receiving an oral dose of 35 mg MPH
      (approximately 0.5 mg/kg) when peak MPH binding was assumed. RESULTS: When
      anticipating reward, dAMPH users showed lower striatal activation in comparison
      to control subjects. In addition, MPH induced a reduction in the striatal
      activation during reward anticipation in healthy controls, whereas no such effect
      was observed in dAMPH users. CONCLUSION: The combination of these findings
      provides further evidence for frontostriatal DAergic dysfunction in recreational
      dAMPH users and is consistent with preclinical data suggesting neurotoxic effects
      of chronic dAMPH use. The findings of this explorative study could have important
      implications for humans in need for treatment with dAMPH, such as patients
      suffering from ADHD and therefore this study needs replication in a larger
      sample.

PMID- 23142494
TI  - Fine-grain analysis of the treatment effect of topiramate on methamphetamine
      addiction with latent variable analysis.
AB  - BACKGROUND: As reported previously, 140 methamphetamine-dependent participants at
      eight medical centers in the U.S. were assigned randomly to receive topiramate
      (N=69) or placebo (N=71) in a 13-week clinical trial. The study found that
      topiramate did not appear to reduce methamphetamine use significantly for the
      primary outcome (i.e., weekly abstinence from methamphetamine in weeks 6-12).
      Given that the treatment responses varied considerably among subjects, the
      objective of this study was to identify the heterogeneous treatment effect of
      topiramate and determine whether topiramate could reduce methamphetamine use
      effectively in a subgroup of subjects. METHODS: Latent variable analysis was used
      for the primary and secondary outcomes during weeks 6-12 and 1-12, adjusting for
      age, sex, and ethnicity. RESULTS: Our analysis of the primary outcome identified
      30 subjects as responders, who either reduced methamphetamine use consistently
      over time or achieved abstinence. Moreover, topiramate recipients had a
      significantly steeper slope in methamphetamine reduction and accelerated to
      abstinence faster than placebo recipients. For the secondary outcomes in weeks 6
      12, we identified 40 subjects as responders (who had significant reductions in
      methamphetamine use) and 65 as non-responders; topiramate recipients were more
      than twice as likely as placebo recipients to be responders (odds ratio=2.67;
      p=0.019). Separate analyses of the outcomes during weeks 1-12 yielded similar
      results. CONCLUSIONS: Methamphetamine users appear to respond to topiramate
      treatment differentially. Our findings show an effect of topiramate on the
      increasing trend of abstinence from methamphetamine, suggesting that a tailored
      intervention strategy is needed for treating methamphetamine addiction.

PMID- 23142495
TI  - Flow and compaction behaviour of ultrafine coated ibuprofen.
AB  - Good flow and compaction properties are prerequisites for successful compaction
      process. Apart from initial profile, mechanical properties of pharmaceutical
      powders can get modified during unit processes like milling. Milled powders can
      exhibit a wide range of particle size distribution. Further downstream processing
      steps like compaction can be affected by this differential particle size
      distribution. This has greatest implications for formulations like high dose
      drugs wherein the active pharmaceutical ingredient (API) contributes the maximum
      bulk in the final formulation. The present study assesses the impact of dry
      coating with ultrafine particles of same material, on the flow and compaction
      properties of the core material. Ibuprofen was selected as model drug as it has
      been reported to have poor mechanical properties. Ultrafine ibuprofen (average
      size 1.75 MUm) was generated by Dyno((r)) milling and was dry coated onto the
      core ibuprofen particles (average size 180 MUm). Compaction studies were
      performed using a fully instrumented rotary tablet press. Compaction data was
      analyzed for compressibility, tabletability, compactibility profiles and Heckel
      plot. Dry coating of the ibuprofen exhibited greater compressibility and
      tabletability, at lower compaction pressure. However, at compaction pressure
      above 220 MPa, compressibility and tabletability of coated as well as uncoated
      materials were found to be similar. Heckel analysis also supported the above
      findings, as P(y) value of uncoated ibuprofen was found to be 229.49 MPa and for
      2.0% ultrafine coated ibuprofen was found to be 158.53 MPa. Lower P(y) value of
      ultrafine coated ibuprofen indicated ease of plastic deformation. Superior
      compressibility and deformation behaviour of ultrafine coated ibuprofen
      attributed to increased interparticulate bonding area. This strategy can also be
      explored for improving tabletability of high dose poorly compressible drugs.

PMID- 23142496
TI  - Biotin uptake by T47D breast cancer cells: functional and molecular evidence of
      sodium-dependent multivitamin transporter (SMVT).
AB  - The objective of this study was to investigate functional and molecular evidence
      of carrier mediated system responsible for biotin uptake in breast cancer (T47D)
      cells and to delineate mechanism of intracellular regulation of this transporter.
      Cellular accumulation of [3H] biotin was studied in T47D and normal mammary
      epithelial (MCF-12A) cells. Reverse transcription polymerase chain reaction (RT
      PCR) was carried out to confirm the molecular expression of sodium dependent
      multivitamin transporter (SMVT) in T47D cells. Quantitative real time PCR
      analysis was also performed to compare the relative expression of SMVT in T47D
      and MCF-12A cells. [3H] biotin uptake by T47D cells was found to be concentration
      dependent with K(m) of 9.24 MUM and V(max) of 27.34 pmol/mg protein/min. Uptake
      of [3H] biotin on MCF-12A cells was also found to be concentration dependent and
      saturable, but with a relatively higher K(m) (53.10 MUM) indicating a decrease in
      affinity of biotin uptake in normal breast cells compared to breast cancer cells.
      [3H] biotin uptake appears to be time-, temperature-, pH- and sodium ion
      dependent but independent of energy and chloride ions. [3H] biotin uptake was
      significantly inhibited in the presence of biotin, its structural analog
      desthiobiotin, pantothenic acid and lipoic acid. Concentration dependent
      inhibition of biotin uptake was evident in the presence of valeric acid which
      possesses free carboxyl group and biocytin and NHS biotin which are devoid of
      free carboxyl group. No significant inhibition was observed in the presence of
      structurally unrelated vitamins (ascorbic acid, folic acid, nicotinic acid,
      thiamine, pyridoxine and riboflavin). Modulators of PTK, PKC and PKA mediated
      pathways had no effect, but uptake in presence of calmidazolium (calcium
      calmodulin inhibitor) was significantly inhibited. [3H] biotin uptake in the
      presence of calmidazolium was found to be saturable with a K(m) and V(max) values
      of 13.49 MUM and 11.20 pmol/mg protein/min, respectively. A band of SMVT mRNA at
      774 bp was identified by RT-PCR analysis. Quantitative real time PCR confirmed
      higher expression of SMVT in T47D cells relative to MCF-12A cells. All these
      studies demonstrated for the first time the functional and molecular expression
      of sodium dependent multivitamin transporter (SMVT), a specific carrier-mediated
      system for biotin uptake, in human derived breast cancer (T47D) cells. The
      present study also indicated that cancer cells could import more vitamin compared
      to normal breast cells possibly for maintaining high proliferative status. We
      investigated the likelihood of selecting this cell line (T47D) as an in vitro
      cell culture model to study biotin-conjugated anti-cancer drugs/drug delivery
      systems.

PMID- 23142497
TI  - Formulation of bioadhesive hexylaminolevulinate pellets intended for photodynamic
      therapy in the treatment of cervical cancer.
AB  - Photodynamic therapy has a great potential in the treatment of cervical cancer.
      The aim of this study was to develop bioadhesive pellets containing
      hexylaminolevulinate (HAL), a precursor of the photoactive substance PpIX, with a
      fast release for vaginal drug delivery. Pellets were produced by
      extrusion/spheronization, and Carbopol((r)) 934 was used to obtain bioadhesive
      properties. A 2(2)-factorial design with center point investigating the HAL
      content (1 and 10%, w/w) and Carbopol((r)) 934 content (1 and 8%, w/w) was set
      up. The most suitable formulations were mechanically stable and showed
      bioadhesive properties toward vaginal tissue. The drug load was released within
      20 min in phosphate buffer pH 4 and 6.8 in the in vitro dissolution test. The
      stability of HAL in the pellet formulations varied, but the most stable
      formulation showed 96-97% HAL remaining in the formulation after 6-7 weeks of
      storage at accelerated temperature conditions (40  degrees C). The investigated
      formulations seem promising for vaginal delivery of HAL.

PMID- 23142498
TI  - NF-kappaB pathway mediates vascular smooth muscle response to nicotine.
AB  - Vascular smooth muscle cells (SMCs) and endothelial cells (ECs) play important
      roles in nicotine-induced cardiovascular disease. To elucidate the mechanism
      underlying the abnormal SMC behavioral response to nicotine, we investigated the
      activation of the NF-kappaB signal transduction pathway and cell adhesion
      molecular (CAM) expression on SMCs. Also we used different cell culture manner of
      SMC sole and EC-SMC co-culture with a 0.4 or a 3 MUm membrane pore, to observe
      whether there is a crosstalk between EC/SMC involved in the process of NF-kappaB
      pathway activation. Nicotine-induced effects were observed in SMCs by both
      monoculture and co-culture with the 3 MUm-pore size, including the
      phosphorylation of IKK and IkappaB, the shift of transcription factor NF-kappaB,
      and the enhancement of SMC cytoskeleton protein expression and migration ability,
      but none were observed by co-culture with the 0.4 MUm-pore size. All of the
      actions could be distinctly blocked by alpha-bungarotoxin (alpha7 nicotinic
      receptor inhibitor) or PDTC (NF-kappaB suppressor). Flow cytometry analysis
      showed that the adhesion molecules ICAM-1 and LFA-1 and VCAM-1 and VLA-4 were
      better expressed similarly on the surface of SMCs in the monoculture and 3 MUm
      pore size co-culture system vs. the 0.4 MUm co-culture way. The results imply
      that nicotine induces SMC cytoskeleton protein up-expression and migration via
      the NF-kappaB signaling pathway and that EC-SMC crosstalk via CAM facilitates its
      response to nicotine.

PMID- 23142499
TI  - Applications of small-angle X-ray scattering to biomacromolecular solutions.
AB  - Small-angle scattering of X-rays (SAXS) is an established method for low
      resolution structural characterization of biological macromolecules in solution.
      Being complementary to the high resolution methods (X-ray crystallography and
      NMR), SAXS is often used in combination with them. The technique provides overall
      three-dimensional structures using ab initio reconstructions and hybrid modeling,
      and allows one to quantitatively characterize equilibrium mixtures as well as
      flexible systems. Recent progress in SAXS instrumentation, most notably, high
      brilliance synchrotron sources, has paved the way for high throughput automated
      SAXS studies allowing screening of external conditions (pH, temperature, ligand
      binding etc.). The modern approaches for SAXS data analysis are presented in this
      review including rapid characterization of macromolecular solutions in terms of
      low-resolution shapes, validation of high-resolution models in close-to-native
      conditions, quaternary structure analysis of complexes and quantitative
      description of the oligomeric composition in mixtures. Practical aspects of SAXS
      as a standalone tool and its combinations with other structural, biophysical or
      bioinformatics methods are reviewed. The capabilities of the technique are
      illustrated by a selection of recent applications for the studies of biological
      molecules. Future perspectives on SAXS and its potential impact to structural
      molecular biology are discussed.

PMID- 23142500
TI  - Intrinsically disordered proteins undergo and assist folding transitions in the
      proteome.
AB  - The common notion in the protein world holds that proteins are synthesized as a
      linear polypeptide chain, followed by folding into a unique, functional 3D
      structure. As outlined in many articles of this volume, this is in fact the case
      for a great proportion of the proteome. Many proteins and protein domains,
      however, are intrinsically disordered (IDPs), i.e., they cannot fold on their
      own, but often undergo a folding transition in the presence of a binding partner.
      This binding-induced folding process shows strong conceptual parallels with the
      folding of globular proteins, in a sense that it can proceed via two routes,
      either induction of the folded conformation from an initial random state or
      selection of a pre-formed state already present in the ensemble. In addition, we
      show that IDPs not only undergo folding themselves, they also assist the folding
      process of other proteins as chaperones, and even contribute to the quality
      control processes of the cell, in which irreparably misfolded proteins are
      recognized and tagged for proteasomal degradation. These various mechanisms
      suggest that structural disorder, in a biological context, is linked with protein
      folding in several ways, in which both the IDP and its partner may undergo
      reciprocal structural transitions.

PMID- 23142501
TI  - Longitudinal changes in lumbar bone mineral density distribution may increase the
      risk of wedge fractures.
AB  - BACKGROUND: Trabecular bone strength diminishes as a result of osteoporosis and
      altered biomechanical loading at the vertebral and spinal levels. The spine
      consists of the anterior, middle and posterior columns and the load supported by
      the anterior and middle columns will differ across different regions of the
      spine. Stress shielding of the anterior column can contribute to bone loss and
      increase the risk of wedge fracture. There is a lack of quantitative data related
      to regional spinal bone mineral density distribution over time. We hypothesize
      that there is an increase in the posterior-to-anterior vertebral body bone
      mineral density ratio and a decrease in whole-body bone mineral density over
      time. METHODS: Bone mineral density was measured in 33 subjects using
      quantitative computed tomography scans for L1-L3 vertebrae, region (anterior and
      posterior vertebral body), and time (baseline and 6 years after). FINDINGS:
      Lumbar bone mineral density decreased significantly (Delta: ~15%) from baseline
      to the 6th year visit. Individual vertebra differences over time (L1: ~14%, L2:
      ~14%, L3: ~17%) showed statistical significance. Anterior bone mineral density
      change was significantly greater than in the posterior vertebral body region
      (Delta anterior: ~18%; Delta posterior: ~13%). Posterior-to-anterior bone mineral
      density ratio was significantly greater in the 6th year compared to baseline
      values (mean (SD), 1.33 (0.2) vs. 1.23 (0.1)). INTERPRETATION: This study
      provides longitudinal quantitative measurement of bone mineral density in
      vertebrae as well as regional changes in the anterior and posterior regions.
      Understanding bone mineral density distribution over time may help to decrease
      the risk of wedge fractures if interventions can be developed to bring spine
      loading to its normal state.

PMID- 23142502
TI  - Establishment and validation of a new semi-chronic dextran sulfate sodium-induced
      model of colitis in mice.
AB  - BACKGROUND: The dextran sulfate sodium (DSS)-induced model of colitis is a
      commonly used model of inflammatory bowel disease (IBD) in animals. However,
      there were few studies on the therapeutic efficacy of drugs for IBD after the
      onset of colitis in this model. We established a semi-chronic model of DSS
      induced colitis in mice and used it to assess the therapeutic efficacy of agents
      for IBD. MATERIALS AND METHODS: Colitis was induced by administration of 3% DSS
      in drinking water to mice for 7days followed by 5days of normal drinking water.
      RESULTS: Ulcerative colitis (UC)-like symptoms including diarrhea, bloody stools
      and body-weight loss were observed from days 3 to 5, and continued until day 12
      after DSS administration. Persistent colitis was associated with sustained local
      production of cytokines and was characterized by infiltration of inflammatory
      cells, crypt loss and erosion in the distal colon. These features are similar to
      those found in patients with UC. In this model, anti-tumor necrosis factor (TNF)
      alpha antibody or anti-interleukin (IL)-12/23p40 antibody significantly
      ameliorated colitis when administered after the onset of colitis. However,
      treatment with FK506, prednisolone or sulfasalazine provided limited therapeutic
      benefit. CONCLUSION: The DSS-induced colitis established here showed similar
      symptomatic and histopathological features to those seen in human UC. This model
      may be available for predicting the clinical efficacy of candidate compounds for
      UC.

PMID- 23142503
TI  - CpG oligodeoxynucleotides with double stem-loops show strong immunostimulatory
      activity.
AB  - Based on the current understanding of TLR9 recognition of CpG ODN, we have tried
      to design a series of CpG ODNs that display double stem-loops when being analyzed
      for their secondary structures using 'mfold web server'. Proliferation of human
      PBMC and bioassay for IFN production were used as technical platforms in primary
      screening. Interestingly, two of them, designated as DSL01 and D-SL03, belonging
      to B class CpG ODN and C class CpG ODN respectively, showed vigorous
      immunostimulatory activity and were chosen for further tests. Flow cytometry
      analysis showed that both of them could activate human B cells, NK cells,
      mononuclear cells and T cells and up-regulate expression of CD80, CD86 and HLA-DR
      on the surface of subsets in human PBMCs. Furthermore, we demonstrated that those
      two ODNs potently stimulated proliferation of PBMC/splenocytes obtained from
      diverse vertebrate species. Noticeably, both of them displayed anti-breast cancer
      effect in mice when administered by peritumoral injection.

PMID- 23142504
TI  - Bothropstoxin-I reduces evoked acetylcholine release from rat motor nerve
      terminals: radiochemical and real-time video-microscopy studies.
AB  - Understanding the biological activity profile of the snake venom components is
      fundamental for improving the treatment of snakebite envenomings and may also
      contribute for the development of new potential therapeutic agents. In this work,
      we tested the effects of BthTX-I, a Lys49 PLA(2) homologue from the Bothrops
      jararacussu snake venom. While this toxin induces conspicuous myonecrosis by a
      catalytically independent mechanism, a series of in vitro studies support the
      hypothesis that BthTX-I might also exert a neuromuscular blocking activity due to
      its ability to alter the integrity of muscle cell membranes. To gain insight into
      the mechanisms of this inhibitory neuromuscular effect, for the first time, the
      influence of BthTX-I on nerve-evoked ACh release was directly quantified by
      radiochemical and real-time video-microscopy methods. Our results show that the
      neuromuscular blockade produced by in vitro exposure to BthTX-I (1 MUM) results
      from the summation of both pre- and postsynaptic effects. Modifications affecting
      the presynaptic apparatus were revealed by the significant reduction of nerve
      evoked [(3)H]-ACh release; real-time measurements of transmitter exocytosis using
      the FM4-64 fluorescent dye fully supported radiochemical data. The postsynaptic
      effect of BthTX-I was characterized by typical histological alterations in the
      architecture of skeletal muscle fibers, increase in the outflow of the
      intracellular lactate dehydrogenase enzyme and progressive depolarization of the
      muscle resting membrane potential. In conclusion, these findings suggest that the
      neuromuscular blockade produced by BthTX-I results from transient depolarization
      of skeletal muscle fibers, consequent to its general membrane-destabilizing
      effect, and subsequent decrease of evoked ACh release from motor nerve terminals.

PMID- 23142505
TI  - Effects of phospholipase A2 and metalloprotease fractions of Russell's viper
      venom on cytokines and renal hemodynamics in dogs.
AB  - Several enzymes in Russell's viper (Daboia siamensis) venom are involved in the
      venom effects and renal injury. The effects of fractional components of Russell's
      viper venom, phospholipase A(2) and metalloprotease fractions, were examined in
      two groups of four experimental dogs each. Animals received an intravenous
      injection of 140 MUg/kg of each venom fraction. The inflammatory effects and
      renal hemodynamic changes were assessed. Plasma concentrations of interleukin-6
      (IL-6), tumor necrosis factor-alpha (TNF-alpha) and PGE2 were elevated by both
      phospholipase A(2) (PLA(2)) and metalloprotease (MP) fractions. The plasma level
      of nitric oxide was increased after PLA(2) fraction injection but not with MP
      fraction injection. Leukocytosis with increase in lymphocytes, monocytes and
      granulocytes was observed after both PLA(2) and MP injections. Results from this
      study suggested that both PLA(2) and MP were inflammatory. Increased red blood
      cell count, hematocrit and hemoglobin concentration were observed in animals
      injected with PLA(2) fraction, but not with MP fraction. Hemodynamically, PLA(2)
      fraction induced marked decrease in mean arterial pressure with decreased renal
      vascular resistance initially followed later by increased renal vascular
      resistance. MP fraction caused less decrease of mean arterial pressure but
      increased renal vascular resistance throughout the experiment. Both enzymes
      decreased renal blood flow, glomerular filtration rate and urine flow. The
      findings indicate vasodilating effect of PLA(2) fraction and vasoconstricting
      effect and decreased cardiac function of MP fraction.

PMID- 23142506
TI  - Novel potassium channel blocker venom peptides from Mesobuthus gibbosus
      (Scorpiones: Buthidae).
AB  - In the present study, we report for the first time, the molecular, biochemical
      and electrophysiological characterization of the components present in the
      soluble venom from Mesobuthus gibbosus (Brulle, 1832). According to the
      epidemiological and clinical situation of scorpion envenomation cases M. gibbosus
      scorpion is one of the most important health-threatening species of Turkey.
      Despite the medical importance reported for M. gibbosus, there is no additional
      information on toxin peptides and venom components to clarify the toxic effect of
      the M. gibbosus sting. Biochemical characterization of the venom was performed
      using different protocols and techniques following a bioassay-guided strategy
      (HPLC, mass spectrometry and Edman degradation sequencing). Venom fractions were
      tested in electrophysiological assays on a panel of six K(+) channels (K(v)1.1
      1.6) by using the two-electrode voltage clamp technique. Three new alpha-KTx
      peptides were found and called MegKTx1, MegKTx2 and MegKTx3 (M. gibbosus, K(+)
      channel toxin number 1-3). A cDNA library from the telson was constructed and
      specific screening of transcripts was performed. Biochemical and molecular
      characterization of MegKTx peptides and transcripts shows a relation with toxins
      of three different alpha-KTx subfamilies (alpha-KTx3.x, alpha-KTx9.x and alpha
      KTx16.x).

PMID- 23142507
TI  - Heteromtoxin (HmTx), a novel heterodimeric phospholipase A(2) from Heterometrus
      laoticus scorpion venom.
AB  - Heteromtoxin (HmTx) is a group III phospholipase A(2) produced in Heterometrus
      laoticus, in Thailand. In this study, HmTx was purified from venom by separation
      chromatography, and the PLA(2) activity of the fractions was determined by
      lecithin agar assay. The enzyme is an acidic protein with a pI of 5.6 and an
      apparent molecular weight of 14018.4 Da. The nucleotide sequence of HmTx contains
      649 bp, and the mature protein is predicted to have 131 amino acid residues-104
      of which make up the large subunit, and 27 of which make up the small subunit.
      The subunit structure of HmTx is highly similar to that of the other toxin,
      Pandinus imperator imperatoxin I (IpTx(i)) and to Mesobuthus tamulus
      phospholipase A(2) (MtPLA(2)). The 3D-structure of HmTx consists of three
      conserved alpha-helices: h1 (Lys24-His34), h2 (Cys59-Asp71), and h3 (Ala80
      Phe89). The beta-sheet consisted of a single stranded anti-parallel beta-sheet
      (b1.1 at Glu43-Lys45 and b1.2 at Lys48-Asn50) that was highly similar to the
      conserved sequences (-CGXG-, -CCXXHDXC- and CXCEXXXXXC-) of Apis mellifera (bee)
      phospholipases.

PMID- 23142508
TI  - Epidemiology of pediatric injury in Malawi: burden of disease and implications
      for prevention.
AB  - PURPOSE: Pediatric injuries pose a significant health burden in sub-Saharan
      Africa, though historic data are too scarce to appreciate the extent of the
      problem. The purpose of this study is to utilize a comprehensive database to
      describe the epidemiology of pediatric injuries at a tertiary hospital in Malawi.
      METHODS: Data were prospectively collected on patients presenting to the
      emergency department for treatment of injuries from 2008 to 2010 (n = 23,625).
      The subset of pediatric patients (n = 7233) underwent cross-sectional analysis to
      examine demographics, injury environment, timing and mechanisms. RESULTS:
      Pediatric patients, (0-16 years) comprised 30.6% of all trauma patients. Mean age
      was 7.2 years. Falls were the most common injury (43%), followed by burns
      (11.1%), pedestrian road traffic injuries (9.7%), foreign bodies (7.5%), and
      assaults (7.2%). Statistically significant differences in injury pattern were
      observed between gender, age groups and season. After logistic regression,
      predictors of fall included male gender, home setting, and rainy season, whereas
      predictors of burn included female gender, age 0-5 yrs, home setting, and cold
      season. Predictors of pedestrian injury included age 6-10 yrs, female, and
      roadside setting. Predictors of foreign body ingestion included age 0-5 yrs,
      female gender, home setting, and daytime, and predictors of assault include male
      gender, age 11-16 yrs, nighttime hours. All predictors were statistically
      significant (p < 0.05). CONCLUSIONS: This study revealed patterns of injury based
      upon age, gender, location, and season. Our results may prove useful to
      stakeholders in injury prevention for designing, evaluating, and implementing
      programs to improve public safety in children in Malawi and similar resource poor
      nations.

PMID- 23142509
TI  - Orthosomella lipae sp. n. (Microsporidia) a parasite of the weevil, Liophloeus
      lentus Germar, 1824 (Coleoptera: Curculionidae).
AB  - A new microsporidium, Orthosomella lipae sp. n., was isolated from the outer
      ovariole sheath, trophic chambers, oocytes, somatic tissues and eggs of adults of
      the weevil, Liophloeus lentus Germar, 1824 (Coleoptera: Curculionidae) from
      southern Poland. Morphological and life cycle characteristics revealed using
      light and electron microscopy, place this new species within the Unikaryonidae.
      However, the 16S rDNA phylogeny indicates that it is associated with the genus
      Orthosomella.

PMID- 23142510
TI  - Life Cycle Assessment of landfill biogas management: sensitivity to diffuse and
      combustion air emissions.
AB  - GOAL AND SCOPE: The life cycle inventory of landfill emissions is a key point in
      Life Cycle Assessment (LCA) of waste management options and is highly subject to
      discussion. Result sensitivity to data inventory is accounted for through the
      implementation of scenarios that help examine how waste landfilling should be
      modeled in LCA. METHOD: Four landfill biogas management options are
      environmentally evaluated in a Life Cycle Assessment perspective: (1) no biogas
      management (open dump), conventional landfill with (2) flaring, (3) combined heat
      and power (CHP) production in an internal combustion engine and (4) biogas
      upgrading for use as a fuel in buses. Average, maximum and minimum literature
      values are considered both for combustion emission factors in flares and engines
      and for trace pollutant concentrations in biogas. RESULTS: Biogas upgrading for
      use as a fuel in buses appears as the most relevant option with respect to most
      non-toxic impact categories and ecotoxicity, when considering average values for
      trace gas concentrations and combustion emission factors. Biogas combustion in an
      engine for CHP production shows the best performances in terms of climate change,
      but generates significantly higher photochemical oxidant formation and marine
      eutrophication impact potentials than flaring or biogas upgrading for use as a
      fuel in buses. INTERPRETATION AND DISCUSSION: However the calculated
      environmental impact potentials of landfill biogas management options depend
      largely on the trace gas concentrations implemented in the model. The use of
      average or extreme values reported in the literature significantly modifies the
      impact potential of a given scenario (up to two orders of magnitude for open
      dumps with respect to human toxicity). This should be taken into account when
      comparing landfilling with other waste management options. Also, the actual
      performances of a landfill top cover (in terms of oxidation rates) and combustion
      technology (in terms of emission factors) appear as key parameters affecting the
      ranking of biogas management options.

PMID- 23142511
TI  - Study of the reuse of treated wastewater on waste container washing vehicles.
AB  - The wheelie bins for the collection of municipal solid waste (MSW) shall be
      periodically washed. This operation is usually carried out by specific vehicles
      which consume about 5000 L of water per day. Wastewater derived from bins washing
      is usually stored on the same vehicle and then discharged and treated in a
      municipal WWTP. This paper presents a study performed to evaluate the reuse of
      the wastewater collected from bins washing after it has been treated in a small
      plant mounted on the vehicle; the advantage of such a system would be the
      reduction of both vehicle dimension and water consumption. The main results
      obtained by coagulation-flocculation tests performed on two wastewater samples
      are presented. The addition of 2 mL/L of an aqueous solution of aluminum
      polychloride (18% w/w), about 35 mL/L of an aqueous solution of CaO (4% w/w) and
      25 mL/L of an aqueous solution of an anionic polyelectrolyte (1 0/00 w/w) can
      significantly reduce turbidity and COD in treated water (to about 99% and 42%,
      respectively); the concomitant increase of UV transmittance at 254 nm (up to 15%)
      enables UV disinfection application by a series of two ordinary UV lamps. Much
      higher UV transmittance values (even higher than 80%) can be obtained by dosing
      powdered activated carbon, which also results in a greater removal of COD.

PMID- 23142512
TI  - Development of fed-batch strategies for the production of streptavidin by
      Streptomyces avidinii based on power input and oxygen supply studies.
AB  - Streptavidin is a tetrameric protein with an extremely high affinity to biotin
      and different biotin-like peptide-tags. This characteristic causes its widespread
      use in biotechnology. Streptavidin is produced by the fermentation of wild type
      Streptomyces avidinii or by recombinant Streptomyces lavendulae, Escherichia
      coli, and Bacillus subtilis strains. However, little is known about the influence
      of power input and oxygen supply as well as feeding strategies on the production
      of streptavidin by S. avidinii. This paper provides a systematic analysis of the
      effect of rotary frequency of the stirrer, leading to a plateau-like streptavidin
      formation behaviour between 400 and 700 min(-1). This plateau was characterized
      by specific power inputs between 79 and 107 W L(-1) and corresponding maximal
      product concentrations of 6.90 MUM in 6 days. Lower as well as higher rotary
      frequencies were not beneficial. Subsequently, a linear fed-batch procedure could
      be established reproducibly yielding 39.20 MUM streptavidin in 14 days,
      characterized by a constant productivity of 114 nM h(-1). Fed-batch procedures
      based on dissolved oxygen were less efficient. The linear feeding strategy
      presented in this paper led to the highest streptavidin concentration ever
      reported and exceeded the maximal product level given in the literature
      drastically by a factor of 8.5.

PMID- 23142513
TI  - Efficient synthesis of phosphatidylserine in 2-methyltetrahydrofuran.
AB  - 2-Methyltetrahydrofuran has recently been described as a promising and green
      solvent. Herein, it was successfully used as the reaction medium for enzyme
      mediated transphosphatidylation of phosphatidylcholine with L-serine with the aim
      of phosphatidylserine synthesis for the first time. Our results indicated that as
      high as 90% yield of phosphatidylserine could be achieved after 12 h combined
      with no byproduct (phosphatidic acid) forming. The present work accommodated a
      facilely and efficiently enzymatic strategy for preparing phosphatidylserine,
      which possessed obvious advantages over the reported processes in terms of high
      efficiency and environmental friendliness. This work is also a proof-of-concept
      opening the use of 2-methyltetrahydrofuran in biosynthesis as well.

PMID- 23142514
TI  - Biocatalytic anti-Prelog stereoselective reduction of ethyl acetoacetate
      catalyzed by whole cells of Acetobacter sp. CCTCC M209061.
AB  - The biocatalytic anti-Prelog stereoselective reduction of ethyl acetoacetate
      (EAA) to ethyl (R)-3-hydroxybutyrate {(R)-EHB} was successfully conducted in the
      aqueous system using immobilized Acetobacter sp. CCTCC M209061 cells. Among
      various microorganisms tested, Acetobacter sp. CCTCC M209061 gave the best
      performance and showed great potential for the bioreduction of EAA to (R)-EHB.
      Acetobacter sp. CCTCC M209061 cells were immobilized on calcium alginate and then
      coated with chitosan, and the immobilized cells clearly surpassed the free cells
      in terms of better thermal stability, storability and recyclability. The optimal
      co-substrate for the reaction was found to be glucose. The optimal substrate
      concentration, buffer pH, glucose concentration, reaction temperature,
      biocatalyst concentration and shaking speed were 35.0 mmol/L, 5.5, 80.0 mmol/L,
      35  degrees C, 0.45 g/mL and 200 rpm, respectively. Under the optimized
      conditions, the initial reaction rate, the yield and the enantiomeric excess
      (e.e.) of the product were 1.28 MUmol/min, 82.6% and above 99.0%, respectively,
      which were much higher than those reported previously. The efficient whole-cell
      biocatalytic process was feasible on a 500-mL preparative scale, and the
      immobilized cells showed excellent operational stability and could be re-used for
      at least 10 batches. Additionally, the product e.e. constantly remained above
      99.0% regardless of re-use cycles of the biocatalyst.

PMID- 23142515
TI  - Adenosine receptor antagonism suppresses functional and histological inflammatory
      changes in the rat urinary bladder.
AB  - Cyclophosphamide (CYP) induces an interstitial cystitis-like inflammation. The
      resulting bladder dysfunction has been associated with increased release of
      adenosine-5'-triphosphate (ATP), structural bladder wall changes and contractile
      impairment. Due to the inflammatory modulatory effects of purines it was
      presently wondered if pre-treatment with P1 and P2 purinoceptor antagonists
      affect the CYP-induced alterations. Rats were pre-treated with saline or
      antagonists for five days, and 60 h before the in vitro functional examination
      the rats were administered either saline or CYP. Histological examination
      revealed CYP-induced bladder wall thickening largely depending on submucosal
      enlargement, mast cell invasion of the detrusor muscle, increase in muscarinic M5
      receptor expression and macrophage migration inhibitory factor (MIF) occurrence
      in large parts of the urothelium. Functionally, methacholine- and ATP-evoked
      contractions were smaller in urinary bladders from CYP-treated rats. Pre
      treatment with the P2 purinoceptor antagonist suramin and the P1A2B antagonist
      PSB1115 did not to any great extent affect the CYP-induced changes. The P1A1
      antagonist DPCPX, however, abolished the difference of methacholine-evoked
      contractions between saline- and CYP-treated rats. ATP-evoked contractions were
      reduced in control after the DPCPX pre-treatment, but not in cystitis. The
      functional observations for DPCPX were supported by its suppression of CYP
      induced submucosal thickening, muscarinic M5 receptor expression and, possibly,
      detrusor mast cell infiltration and the spread of urothelial MIF occurrence.
      Thus, P1A1 is an important pro-inflammatory receptor in the acute CYP-induced
      cystitis and a P1A1 blockade during the initial phase may suppress CYP-induced
      cystitis. P1A1 purinoceptors seem to regulate contractility in healthy and in
      inflamed rat urinary bladders.

PMID- 23142516
TI  - Absence of beta-amyloid in cortical cataracts of donors with and without
      Alzheimer's disease.
AB  - Eye lenses from human donors with and without Alzheimer's disease (AD) were
      studied to evaluate the presence of amyloid in cortical cataract. We obtained 39
      lenses from 21 postmortem donors with AD and 15 lenses from age-matched controls
      provided by the Banco de Ojos para Tratamientos de la Ceguera (Barcelona, Spain).
      For 17 donors, AD was clinically diagnosed by general physicians and for 4 donors
      the AD diagnosis was neuropathologically confirmed. Of the 21 donors with AD, 6
      had pronounced bilateral cortical lens opacities and 15 only minor or no cortical
      opacities. As controls, 7 donors with pronounced cortical opacities and 8 donors
      with almost transparent lenses were selected. All lenses were photographed in a
      dark field stereomicroscope. Histological sections were analyzed using a standard
      and a more sensitive Congo red protocol, thioflavin staining and beta-amyloid
      immunohistochemistry. Brain tissue from two donors, one with cerebral amyloid
      angiopathy and another with advanced AD-related changes and one cornea with
      lattice dystrophy were used as positive controls for the staining techniques.
      Thioflavin, standard and modified Congo red staining were positive in the control
      brain tissues and in the dystrophic cornea. Beta-amyloid immunohistochemistry was
      positive in the brain tissues but not in the cornea sample. Lenses from control
      and AD donors were, without exception, negative after Congo red, thioflavin, and
      beta-amyloid immunohistochemical staining. The results of the positive control
      tissues correspond well with known observations in AD, amyloid angiopathy and
      corneas with lattice dystrophy. The absence of staining in AD and control lenses
      with the techniques employed lead us to conclude that there is no beta-amyloid in
      lenses from donors with AD or in control cortical cataracts. The inconsistency
      with previous studies of Goldstein et al. (2003) and Moncaster et al. (2010),
      both of which demonstrated positive Congo red, thioflavin, and beta-amyloid
      immunohistochemical staining in AD and Down syndrome lenses, is discussed.

PMID- 23142517
TI  - Prediction of fluid responsiveness in patients admitted to the medical intensive
      care unit.
AB  - PURPOSE: Accurate prediction of fluid responsiveness is of importance in the
      treatment of patients admitted to the intensive care unit (ICU). We investigated
      whether physical examination, central venous pressure (CVP), central venous
      oxygen saturation (ScvO2), passive leg raising (PLR) test, and transpulmonary
      thermodilution (TPTD)-derived parameters can predict volume responsiveness in
      patients admitted to the ICU. MATERIALS AND METHODS: In this prospective study,
      structured clinical examination, measurement of CVP and ScvO2, a PLR test, and
      TPTD measurements were performed in 31 patients. A fluid challenge test was
      performed in 24 patients (fluid responsiveness was defined as a cardiac index
      [CI] increase of >= 15%). RESULTS: Physical examination, CVP, ScvO2, the PLR
      test, and the TPTD-derived volumetric preload parameter global end-diastolic
      volume index showed poor prognostic capabilities regarding prediction of fluid
      responsiveness. Twenty-nine percent of patients were fluid responsive. There was
      a statistically significant correlation between the fluid challenge-induced
      increase in CI and changes in global end-diastolic volume index (r = 0.666, P <
      .001). In only 17% of patients, CI did not increase after fluid loading.
      CONCLUSIONS: Prediction of fluid responsiveness is difficult using physical
      examination, CVP, ScvO2, PLR maneuver, or TPTD-derived variables in critically
      ill patients. A volume challenge test should be considered for the assessment of
      fluid responsiveness in critically ill patients admitted to the ICU.

PMID- 23142518
TI  - Age related differences in maximal and rapid torque characteristics of the leg
      extensors and flexors in young, middle-aged and old men.
AB  - The decline in maximal and rapid isometric torque characteristics may compromise
      functional living abilities in aging adults while loco-motor muscle groups, such
      as the leg extensors and flexors, may exhibit different torque-time age related
      decreases. The purpose of the present study was to examine the age-related
      differences in maximal and rapid torque characteristics of the leg extensor and
      flexor muscle groups in young, middle-aged, and old men. Sixty-five healthy men
      were categorized by age as young (n=25; mean+/-SD age=24.9+/-3.0 years), middle
      aged (n=22; age=50.6+/-4.0 years), and old (n=18; age=66.8+/-4.5 years).
      Participants performed maximal voluntary contractions (MVCs) of the leg extensors
      and flexors and an estimated thigh cross sectional area (eThighCSA) assessment.
      Peak torque (PT), peak rate of torque development (RTDpeak), absolute RTD and the
      contractile impulse (IMPULSE) were calculated at time intervals of 30, 50, 100
      and 200 ms from the torque-time curve. Relative RTD was calculated at 10, 20, 30,
      40 and 50% of MVC from the normalized torque-time curves. PT, RTDpeak and later
      rapid torque variables (RTD100, RTD200, and IMPULSE200) were greater (P<=0.05) in
      the young and middle-aged when compared to the old men for both muscle groups.
      Early (RTD30,50; IMPULSE30,50) and late (IMPULSE100) rapid torque variables were
      greater (P<=0.05) for the young and middle-aged than the old men for the leg
      extensors but not the leg flexors, except for RTD30, in which there was no
      difference between young and old. There were no differences for all relative RTD
      variables between age groups (P>0.05). eThighCSA was lower in the old compared to
      the young (P=0.001) and middle-aged (P=0.016) men. Maximal and rapid torque
      characteristics were preserved in middle-aged men but greatly reduced in older
      men with differential effects at early and late portions of the torque-time curve
      between the leg extensors and flexors. Significant decreases in absolute maximal
      and rapid torque production with no change in relative RTD across age groups and
      lower eThighCSA in old men may suggest that the loss of rapid torque producing
      capacities observed in older men may be largely a function of mechanisms
      associated with loss of muscle strength and muscle mass.

PMID- 23142519
TI  - Cortical area inducing chewing-like rhythmical jaw movements and its connections
      with thalamic nuclei in guinea pigs.
AB  - Repetitive electrical stimulation to the cortical masticatory areas (CMA) evokes
      rhythmical jaw movements (RJM), whose patterns vary depending on the stimulation
      site, in various species. In guinea pigs, although alternating bilateral jaw
      movements are usually seen during natural chewing, it is still unclear which
      cortical areas are responsible for chewing-like RJM. To address this issue, we
      first defined the cortical areas inducing chewing-like RJM by intracortical
      microstimulation. Stimulation of the most lateral area of the CMA, the granular
      cortex, induced chewing-like RJM, but from the region medial to this area, simple
      vertical RJM were induced. Subsequently, to reveal the properties of these two
      areas in the CMA, the connections between the CMA and the dorsal thalamus were
      examined by neuronal tract-tracing techniques. The area inducing chewing-like RJM
      possessed strong reciprocal connections, mainly with the medial part of the
      ventral posteromedial nucleus, which is the sensory-relay thalamus. On the other
      hand, the simple vertical RJM-inducing area had reciprocal connections with the
      motor thalamus. The present study suggests that the CMA inducing chewing-like RJM
      is different from the CMA inducing simple vertical RJM, and plays a role in
      cortically induced chewing-like RJM under the influence of the sensory thalamus
      in guinea pigs.

PMID- 23142520
TI  - Preactivation of human MSCs with TNF-alpha enhances tumor-suppressive activity.
AB  - Mesenchymal stem/stromal cells (MSCs) can either suppress or promote tumors. We
      found previously that incubation of human bone marrow MSCs (hMSCs) with TNF-alpha
      upregulated multiple genes including TRAIL, which has cancer apoptotic activity.
      Here, we show that weekly infusions into mice of hMSCs preactivated with TNF
      alpha inhibited the progression of lung tumors formed from MDA-MB-231 breast
      cancer cells (MDA). In coculture, preactivated hMSCs induced apoptosis in MDA and
      several other TRAIL-sensitive cancer cell lines. TRAIL was further upregulated by
      apoptotic MDA cells in a TLR3-dependent manner; this feedforward cycle increased
      MDA cell apoptosis, and the chemotherapeutic drug doxorubicin had a synergistic
      effect. Also, activated hMSCs secreted DKK3 to suppress MDA cell cycling, leading
      to a decrease in beta-catenin and cyclin D1/D3 and an increase in p21. Thus,
      culturing hMSCs with TNF-alpha enhances their tumor-suppressive properties and
      may represent a useful strategy to develop hMSC-based approaches for the
      treatment of cancer.

PMID- 23142522
TI  - Understanding resistance to targeted cancer drugs through loss of function
      genetic screens.
AB  - Comprehensive analysis of cancer genomes has provided important insights in the
      critical alterations that confer proliferation and survival advantage to the
      tumor, so-called driver mutations. Tumors harboring these genetic changes
      frequently exhibit striking sensitivities to inhibition of these oncogenic driver
      pathways, a principle referred to as oncogene addiction. Substantial progress has
      been made in the development of drugs that specifically target components of the
      pathways that are associated with these driver mutations. This has enabled the
      first steps in a shift from the use of cytotoxic drugs to highly selective
      targeted therapeutic agents for the treatment of cancer. Unfortunately, despite
      the expanding development of targeted anti-cancer strategies, treatment failure
      due to primary or acquired resistance is still an almost inevitable outcome in
      most advanced human cancers. Understanding drug resistance mechanisms will help
      design more efficient combination treatment strategies that help block resistance
      mechanisms before they become clinically manifest. In this review, we discuss how
      RNA interference functional genetic screens can be used to identify clinically
      relevant mechanisms of drug resistance and how this technology can be used to
      develop effective combination therapies.

PMID- 23142521
TI  - Attenuation of miR-126 activity expands HSC in vivo without exhaustion.
AB  - Lifelong blood cell production is governed through the poorly understood
      integration of cell-intrinsic and -extrinsic control of hematopoietic stem cell
      (HSC) quiescence and activation. MicroRNAs (miRNAs) coordinately regulate
      multiple targets within signaling networks, making them attractive candidate HSC
      regulators. We report that miR-126, a miRNA expressed in HSC and early
      progenitors, plays a pivotal role in restraining cell-cycle progression of HSC in
      vitro and in vivo. miR-126 knockdown by using lentiviral sponges increased HSC
      proliferation without inducing exhaustion, resulting in expansion of mouse and
      human long-term repopulating HSC. Conversely, enforced miR-126 expression
      impaired cell-cycle entry, leading to progressively reduced hematopoietic
      contribution. In HSC/early progenitors, miR-126 regulates multiple targets within
      the PI3K/AKT/GSK3beta pathway, attenuating signal transduction in response to
      extrinsic signals. These data establish that miR-126 sets a threshold for HSC
      activation and thus governs HSC pool size, demonstrating the importance of miRNA
      in the control of HSC function.

PMID- 23142523
TI  - Single-nucleotide polymorphisms in genes encoding toll-like receptor -2, -3, -4,
      and -9 in a case-control study with bladder cancer susceptibility in a North
      Indian population.
AB  - BACKGROUND AND AIMS: Impairment of the immune system may contribute to the risk
      for having cancer as Toll-like receptors are important for innate immunity. We
      examined the association between candidate disease-susceptibility polymorphisms
      in the single nucleotide polymorphism (SNPs) like TLR2 (-196 to-174del), TLR3
      (C1377T), TLR4 (Thr399Ile) and TLR9 (G2848A) genes in patients with bladder
      cancer in a North Indian population. METHODS: SNPs were comprised of TLR2 (-196
      to -174 Del), TLR3(C1377T), TLR4 (Thr399Ile) and TLR9 (G2848A) genes. Allelic and
      genotypic frequencies of these TLRs SNP from histopathologically confirmed
      patients of bladder cancer (n = 200) and unrelated healthy controls of similar
      ethnicity (n = 200) were genotyped by polymerase chain reaction restriction
      fragment length polymorphism (PCR-RFLP) analysis. RESULTS: In TLR2 I/D gene
      polymorphism, the combination of ID+DD showed a significant 3-fold increased risk
      (p = 0.001). TLR2 with heterozygous genotype ID showed a 3-fold risk and
      combination of heterozygous and variant genotype (ID+DD) also showed a 5-fold
      risk with tumor stage/grade of patients with bladder cancer. The other genotypes
      of TLR3, 4 and 9 did not exhibit any significant association with bladder cancer
      risk. CONCLUSIONS: Our results suggested the involvement of TLR2 (-196 to-174
      del) in bladder cancer susceptibility; however, TLR3, 4 and 9 genes were not
      associated with risk of bladder cancer, implicating that polymorphisms in these
      tested TLRs genes are not likely to be associated with increased risk for
      developing bladder cancer. Functional studies in ethnically diverse populations
      may provide a more comprehensive involvement of innate immunity in identifying
      the disease-associated variants for the etiology of bladder cancer.

PMID- 23142524
TI  - Apolipoprotein E gene polymorphism in psoriasis: a meta-analysis.
AB  - BACKGROUND AND AIMS: Several studies have shown that the apolipoprotein E (ApoE)
      gene is associated with the development of psoriasis. However, there is a
      controversy. The aim of the present study was to evaluate the association of
      psoriasis risk with ApoE polymorphisms. METHODS: We carried out a systematic
      search of studies that explored associations between ApoE polymorphisms and
      psoriasis. The genotype distribution of the control group in each study was
      calculated to determine whether or not there was compliance with the Hardy
      Weinberg equilibrium. Overall effect sizes were assessed by odds ratio (OR) with
      95% confidence intervals (CI). The selection to use the random-effects model or
      fixed-effects model depended on the size of the heterogeneity among the included
      studies. The fail-safe number (Nfs) was used to test the potential publication
      bias. We analyzed the data using Stata v.10.0. RESULTS: A total of seven studies
      with 966 patients and 1,086 controls were included. The results indicated that
      the epsilon2 allele was associated with increased risk of psoriasis (epsilon2 vs.
      epsilon3+epsilon4: OR = 1.47, 95% CI = 1.23-1.75, p <0.05), whereas the epsilon3
      allele and epsilon3/epsilon3 genotype may decrease risk of psoriasis (OR = 0.71,
      95% CI = 0.62-0.82, p <0.05; OR = 0.63, 95% CI = 0.52-0.77, p <0.05,
      respectively). In the subgroup analysis according to ethnicity, the increased
      risk of psoriasis remained in the Asian and European populations, whereas no
      significant association was found in other populations for other polymorphisms.
      CONCLUSIONS: Our study suggests that the ApoE polymorphisms are associated with
      the risk of psoriasis, especially epsilon2 and epsilon3 alleles. Further studies
      are needed to confirm our results.

PMID- 23142525
TI  - Role of tau protein in neuronal damage in Alzheimer's disease and Down syndrome.
AB  - Neurodegenerative disorders constitute a growing concern worldwide. Their
      incidence has increased steadily, in particular among the elderly, a high-risk
      population that is becoming an important segment of society. Neurodegenerative
      mechanisms underlie many ailments such as Parkinson's disease, Huntington's
      disease, Alzheimer's disease (AD) and Down syndrome (DS, trisomy 21).
      Interestingly, there is increasing evidence suggesting that many such diseases
      share pathogenic mechanisms at the cellular and subcellular levels. These include
      altered protein misfolding, impaired autophagy, mitochondrial dysfunction,
      membrane damage, and altered axonal transport. Regarding AD and DS, the first
      common link comes from observations that DS patients undergo AD-like pathology
      early in adulthood. Also, the gene encoding for the amyloid precursor protein is
      present in human autosome 21 and in murine chromosome 16, an animal model of DS.
      Important functions related to preservation of normal neuronal architecture are
      impaired in both conditions. In particular, the stable assembly of microtubules,
      which is critical for the cytoskeleton, is impaired in AD and DS. In this
      process, tau protein plays a pivotal role in controlling microtubule stability.
      Abnormal tau expression and hyperphosphorylation are common features in both
      conditions, yet the mechanisms leading to these phenomena remain obscure. In the
      present report we review possible common mechanisms that may alter tau expression
      and function, in particular in relation to the effect of certain overexpressed DS
      related genes, using cellular models of human DS. The latter contributes to the
      identification of possible therapeutic targets that could aid in the treatment of
      both AD and DS.

PMID- 23142526
TI  - Identification of several sub-populations in the pool of light harvesting
      proteins in the pennate diatom Phaeodactylum tricornutum.
AB  - Diatoms are major contributors to the photosynthetic productivity of marine
      phytoplankton. In these organisms, fucoxanthin-chlorophyll proteins (FCPs) serve
      as light-harvesting proteins. We have explored the FCP complexes in Phaeodactylum
      tricornutum under low light (LL) and high light (HL) conditions. Sub
      fractionating the pool of major FCPs yielded different populations of trimeric
      complexes. Only Lhcf and Lhc-like proteins were found in the trimers. Under LL,
      the first polypeptide fraction contained six different Lhcfs and was mainly
      composed of Lhcf10. It was characterised by the highest amount of fucoxanthin
      (Fx). The second was dominated by Lhcf10, Lhcf5 and Lhcf2, and had a lower Fx/Chl
      c ratio. Little Fx/Chl c also characterised the most abundant FCP complexes,
      found in fraction 3, composed mainly of Lhcf5. These FCPs bound Fx molecules with
      the strongest bathochromic shift. The last two fractions contained FCP complexes
      that were built mainly of Lhcf4, harbouring more Fx molecules that absorbed at
      shorter wavelengths. Under HL, the same main polypeptides were retrieved in the
      different fractions and spectroscopic features were almost identical except for a
      higher diadinoxanthin content. The total amount of Lhcf5 was reduced under HL,
      whereas the amount of the last two fractions and thereby Lhcf4 was increased.
      Lhcf11 was identified in different LL fractions, but not detected in any HL
      fraction, while two new Lhc-like proteins were only found under HL. This is the
      first report on different trimeric FCP complexes in pennate diatoms, which differ
      in polypeptide composition and pigmentation, and are differentially expressed by
      light.

PMID- 23142527
TI  - Electrochemical behaviour of bacterial nitric oxide reductase-evidence of low
      redox potential non-heme Fe(B) gives new perspectives on the catalytic mechanism.
AB  - Nitric oxide reductase (NOR) is a membrane bound enzyme involved in the metabolic
      denitrification pathway, reducing nitric oxide (NO) to nitrous oxide (N(2)O),
      subsequently promoting the formation of the NN bond. Three types of bacterial NOR
      are known, namely cNOR, qNOR and qCuNOR, that differ on the physiological
      electron donor. cNOR has been purified as a two subunit complex, the NorC,
      anchored to the cytoplasmic membrane, with a low-spin heme c, and the NorB
      subunit showing high structural homology with the HCuO subunit I, comprising a
      bis-histidine low-spin heme b and a binuclear iron centre. The binuclear iron
      centre is the catalytic site and it is formed by a heme b(3) coupled to a non
      heme iron (Fe(B)) through a MU-oxo bridge. The catalytic mechanism is still under
      discussion and three hypotheses have been proposed: the trans-mechanism, the cis
      Fe(B) and the cis-heme b(3) mechanisms. In the present work, the Pseudomonas
      nautica cNOR electrochemical behaviour was studied by cyclic voltammetry (CV),
      using a pyrolytic graphite electrode modified with the immobilised protein. The
      protein redox centres were observed and the formal redox potentials were
      determined. The binuclear iron centre presents the lowest redox potential value,
      and discrimination between the heme b(3) and Fe(B) redox processes was attained.
      Also, the number of electrons involved and correspondent surface electronic
      transfer rate constants were estimated. The pH dependence of the observed redox
      processes was determined and some new insights on the NOR catalytic mechanism are
      discussed.

PMID- 23142529
TI  - Influence of a valgus knee brace on muscle activation and co-contraction in
      patients with medial knee osteoarthritis.
AB  - The purpose of this study was to analyse the effect of a valgus knee orthosis
      designed for patients with knee osteoarthritis on the electromyographic activity
      (EMG) of seven muscles of the lower limb during gait. Twelve patients with medial
      knee osteoarthritis walked on a treadmill in three different conditions: without
      orthosis, with a knee orthosis in 4 degrees  valgus adjustment and with an
      orthosis in a neutral flexible adjustment. Root-mean-square (RMS) was analysed in
      each condition during a 150 ms pre-activation phase and during the stance phase
      of gait, which was divided in four sub-phases. In addition, co-contraction ratios
      (CCRs) were calculated between extensor/flexor, medial/lateral muscles and
      between agonist and antagonist muscle pairs. Significant decreases in muscle
      activity and CCRs were observed with the use of the knee orthosis in both
      adjustments compared to the condition without orthosis. Using the valgus brace,
      medial/lateral CCR decreased significantly during the late stance and the
      flexor/extensor CCR decreased significantly during the loading phase and late
      stance. Decreases of muscle pairs CCRs were observed with the neutral flexible
      adjustment. The results support the theory of a possible beneficial effect of
      knee braces in reducing knee loading by decreasing muscle activation and co
      contraction levels, which could contribute to decelerate disease progression in
      patients with knee osteoarthritis.

PMID- 23142528
TI  - Urine arsenic and prevalent albuminuria: evidence from a population-based study.
AB  - BACKGROUND: Long-term arsenic exposure is a major global health problem. However,
      few epidemiologic studies have evaluated the association of arsenic with kidney
      measures. Our objective was to evaluate the cross-sectional association between
      inorganic arsenic exposure and albuminuria in American Indian adults from rural
      areas of Arizona, Oklahoma, and North and South Dakota. STUDY DESIGN: Cross
      sectional. SETTING & PARTIPANTS: Strong Heart Study locations in Arizona,
      Oklahoma, and North and South Dakota. 3,821 American Indian men and women aged 45
      74 years with urine arsenic and albumin measurements. PREDICTOR: Urine arsenic.
      OUTCOMES: Urine albumin-creatinine ratio and albuminuria status. MEASUREMENTS:
      Arsenic exposure was estimated by measuring total urine arsenic and urine arsenic
      species using inductively coupled plasma mass spectrometry (ICPMS) and high
      performance liquid chromatography-ICPMS, respectively. Urine albumin was measured
      by automated nephelometric immunochemistry. RESULTS: The prevalence of
      albuminuria (albumin-creatinine ratio >=30 mg/g) was 30%. Median value for the
      sum of inorganic and methylated arsenic species was 9.7 (IQR, 5.8-15.6) MUg per
      gram of creatinine. Multivariable-adjusted prevalence ratios of albuminuria
      (albumin-creatinine ratio >=30 mg/g) comparing the 3 highest to lowest quartiles
      of the sum of inorganic and methylated arsenic species were 1.16 (95% CI, 1.00
      1.34), 1.24 (95% CI, 1.07-1.43), and 1.55 (95% CI, 1.35-1.78), respectively (P
      for trend <0.001). The association between urine arsenic and albuminuria was
      observed across all participant subgroups evaluated and was evident for both
      micro- and macroalbuminuria. LIMITATIONS: The cross-sectional design cannot rule
      out reverse causation. CONCLUSIONS: Increasing urine arsenic concentrations were
      cross-sectionally associated with increased albuminuria in a rural US population
      with a high burden of diabetes and obesity. Prospective epidemiologic and
      mechanistic evidence is needed to understand the role of arsenic as a kidney
      disease risk factor.

PMID- 23142530
TI  - Obstacle avoidance in Down syndrome.
AB  - INTRODUCTION: The ability to avoid obstacles requires to represent the properties
      of the obstacle, represent the location of the obstacle relative to the body and
      update these representations as the body moves. Individuals with Down syndrome
      (DS) often have trouble avoiding obstacles, leading to increased frequency of
      trips and falling. The aim of the present study was to deeply analyze obstacle
      avoidance strategies in normally developed young adults (N) and in young adults
      with DS, at different levels of obstacle heights, with particular attention to
      the strategies used for clearing the obstacle and to how the walking pattern was
      modified by obstacle perception. METHODS: 10 DS and 16 age-matched N walked along
      a walkway in three conditions: plain walking, walking with obstacle at ground
      level, walking with obstacle at 10% of the subject's height. Spatiotemporal
      parameters were analyzed. RESULTS: There was evidence for a different avoidance
      strategy in DS, and for a difficulty in regulating gait parameters when
      challenged with a complex situation as the presence of an obstacle. This may lead
      to an increased risk of fall. The results in addition suggested a lack in
      anticipatory movement adjustments in DS and provided further evidence of the
      presence of difficulties in perceptual-motor coupling in DS.

PMID- 23142531
TI  - Relationship between ventilatory threshold and muscle fiber conduction velocity
      responses in trained cyclists.
AB  - The relationship between surface electromyography (SEMG) amplitude and the
      ventilatory threshold has been extensively studied. However, previous studies of
      muscle fiber conduction velocity (MFCV) are scarce and present insufficient
      evidence concerning the relationship between MFCV and metabolic responses during
      cycling. Based on that fact, the purpose of this study is twofold: (1) to
      investigate the existence of a MFCV threshold (MFCVT) during cycling and (2) to
      verify if this possible breakpoint is correlated with the ventilatory threshold
      (VT) and the SEMG threshold (SEMGT). Eight trained male cyclists (age 36.0+/
      9.7years) performed an incremental cycling test with initial workload of 150W
      gradually incremented by 20Wmin(-1) until the exhaustion. Gas analyses were
      conducted using a breath-by-breath open-circuit spirometry and SEMG were
      registered from vastus lateralis in each pedaling cycle with a linear array of
      electrodes. A bi-segmental linear regression computer algorithm was used to
      estimate VT, MFCVT and SEMGT respectively in the carbon dioxide production
      (VCO2), MFCV and electromyography root mean square (EMG RMS) curves. The one way
      ANOVA for repeated measures did not reveal any significant difference among VT
      (77.1+/-7.5% of VO2max), MFCVT (80.3+/-10.4% of VO2max) and SEMGT (81.9+/-11.7%
      of VO2max). The Bland and Altman procedure confirmed a good concordance between
      SEMGT and VT (Bias=5.5 of %VO2max) as well as MFCVT and VT (Bias=5.2 of %VO2max).
      The present findings suggest that muscle fiber conduction velocity threshold is a
      valid and reliable non-invasive tool to obtain information about ventilatory
      threshold in trained cyclists.

PMID- 23142532
TI  - Triceps surae activation is altered in male runners with Achilles tendinopathy.
AB  - Achilles tendinopathy is a common injury in running sports however the exact
      etiology of Achilles injury is still unclear. In recent years, altered neuromotor
      recruitment patterns of the triceps surae have been hypothesized to create
      differential intra-tendinous loads leading to pathology; however, this hypothesis
      has not been investigated. Further, the effect foot orthoses may have on
      neuromotor recruitment of the triceps surae in Achilles tendinopathy has not been
      investigated. METHODS: The electromyographic activity of the triceps surae was
      recorded during an over-ground running task. Fifteen Achilles injured
      participants and 19 asymptomatic controls were assessed in a footwear only
      condition. The Achilles injured participants were also assessed running in a pre
      fabricated foot orthoses. RESULTS: In Achilles injured participants, there was a
      significant difference between soleus and lateral gastrocnemius offset times
      during running compared to the asymptomatic controls (p<0.05). There were no
      significant differences in triceps surae muscle activity between the footwear
      only and footwear and orthoses condition in the Achilles injured participants.
      CONCLUSIONS: The finding that triceps surae activity is altered in participants
      with Achilles tendinopathy may have clinical importance as it suggests that intra
      tendinous loads are altered which may contribute to pathological changes.
      Further, foot orthoses have no immediate effect on the neuromotor control of the
      triceps surae.

PMID- 23142533
TI  - Animal models of schizophrenia for molecular and pharmacological intervention and
      potential candidate molecules.
AB  - Schizophrenia is a severe and common psychiatric disease with a lifetime
      prevalence of 0.5% to 1% globally. Because of limitations of the experimental
      approach in humans, valid animal models are essential in the effort to identify
      novel therapeutics for schizophrenia. In most animal models of schizophrenia,
      second generation antipsychotic drugs are reported to be effective in
      ameliorating behavioral abnormalities, while clinical evidence indicates that
      some of the patients are resistant to the antipsychotic drug therapy.
      Accordingly, animal models of antipsychotic drug-resistant schizophrenia are
      needed for screening of novel agents that may be more effective than the existing
      antipsychotic drugs. Furthermore, utilization of appropriate behavioral tasks
      with reference to human testing is essential to facilitate the development of
      novel pharmacotherapeutic approaches for the treatment in schizophrenia.
      Experimental data suggest that there are different types of potential candidate
      molecules as novel antipsychotic drugs with some therapeutic effects on negative
      symptoms and cognitive deficits in schizophrenia. It is proposed that to develop
      novel antipsychotic drugs the efficacy of potential candidate molecules should be
      evaluated using animal models for treatment-resistant schizophrenia with
      appropriate behavioral tasks in reference to human testing.

PMID- 23142534
TI  - Prevalence and risk factors for metabolic syndrome in Medellin and surrounding
      municipalities, Colombia, 2008-2010.
AB  - OBJECTIVE: We assessed the prevalence of and risk factors for metabolic syndrome
      (MetS) among adults 25-64 years of age from Medellin and surrounding
      municipalities, Colombia. METHOD: We used 2008-2010 data from the Antioquia
      STEPwise approach to Surveillance (STEPS), a multi-stage complex cross-sectional
      survey designed according to World Health Organization guidelines. The revised
      2005 International Diabetes Federation definition of MetS was used. RESULTS:
      There were a total of 3000 participants. Of these, 21.4% had high blood pressure
      (HBP) and 64% had abdominal obesity (AO). In the subsample with serum data (n =
      943), 19.8% had high fasting serum glucose, 43.9% had high triglycerides (HTG),
      and 56.6% had low HDL cholesterol (L-HDL). Among those with data to define MetS
      (n = 901), 41% had MetS. Older age was associated with MetS and all components
      except L-HDL. Female sex [odds ratio (OR) = 2.85, 95% confidence interval (CI):
      2.20-3.70], being married (OR = 1.40, CI: 1.09-1.82), and high physical activity
      (OR = 0.59, CI: 0.39-0.91) were associated with AO, smoking with HTG (OR = 1.76,
      CI: 1.16-2.67) and L-HDL (OR = 1.67, CI: 1.10-2.51) and rural residence with HBP
      (OR = 3.42, CI: 1.83-6.37) and L-HDL (OR = 1.18, CI: 1.10-2.51). CONCLUSION: The
      prevalence of MetS and AO was high in this Colombian region. Targeted strategies
      for promoting healthy behaviors are needed.

PMID- 23142535
TI  - Linking culture and structure: adding time and environment--a commentary.

PMID- 23142536
TI  - Pretreatment with valproic acid, a histone deacetylase inhibitor, enhances the
      sensitivity of the peripheral blood micronucleus assay in rodents.
AB  - Micronucleus (MN) assay is widely used for the determination of the genotoxic
      potential of new chemical entities. Improvement in the sensitivity of MN assay
      will be advantageous for the successful detection of marginally active
      genotoxins. In the past, several improvements have been made in the automated
      scoring of micronuclei, while very few attempts have been taken to improve the
      sensitivity of manual micronuclei detection. The present study aims to validate
      the effect of valproic acid (VPA) pretreatment on the sensitivity of peripheral
      blood micronucleus (PBMN) assay using cyclophosphamide (CP, 50mg/kg),
      methotrexate (MTX, 20mg/kg) and zidovudine (AZT, 400mg/kg) in rodents. However,
      to find out the optimum VPA pretreatment time as well as to detect the effect of
      species and age difference, separate experiments were conducted on young Swiss
      albino mice (24-28 days) and Sprague-Dawley rats (21-24 days), in which
      significant increase in MN induction was observed with 3-day VPA pretreatment in
      both the species. Based on these results, studies on adult mice were conducted
      with 3-day VPA pretreatment along with CP or MTX or AZT. The results of the
      present study clearly demonstrate that the 3-day VPA pretreatment significantly
      enhances the sensitivity of PBMN assay in peripheral blood (PB) in adult mice.
      After validation with other standard genotoxins as well as other HDAC (histone
      deacetylase) inhibitors, this model may be useful for the detection of marginally
      active DNA damaging agents.

PMID- 23142537
TI  - Bisphenol A at concentrations found in human serum induces aneugenic effects in
      endothelial cells.
AB  - Bisphenol A (BPA) is an endocrine disrupting chemical to which humans are
      exposed. Continuous environmental exposure to BPA leads to its detection in the
      majority of individuals from developed countries, with serum concentrations
      ranging from 0.5 to 10ng/ml in the general population and much higher when
      associated with occupational exposure. In this work, human umbilical vascular
      endothelial cells (HUVEC) and human colon adenocarcinona (HT29) cell lines were
      used to represent endothelial and digestive-tract tissues, which are in direct
      contact to BPA in vivo. Our results demonstrate that BPA has cell-type
      differential effects. Notably, BPA concentrations commonly found in humans induce
      micronucleus formation and interfere with cell-division processes in endothelial
      cells, resulting in mitotic abnormalities. We also found that BPA induces up
      regulation of two genes encoding proteins associated with chromosome segregation,
      namely CDCA8 (borealin/cell division cycle A8) and SGOL2 (shugoshin-like2). Taken
      together, the aneugenic effects observed in endothelial cells (HUVECs)
      substantiate increasing concerns about BPA exposure at levels currently detected
      in humans.

PMID- 23142538
TI  - Effect of developmental dioxin exposure on methylation and expression of specific
      imprinted genes in mice.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an endocrine disruptor affecting
      the reproductive system in humans. The aim of this study was to evaluate the
      effects of TCDD administered to pregnant mice at two different doses (2-10
      ng/kg/day), on imprinted genes in the male offspring. The degree of methylation
      and the mRNA expression of Snrpn, Peg3 and Igf2r were analyzed in the sperm,
      skeletal muscle and liver. TCDD administration (10 ng/kg/day) decreased the sperm
      count in the male offspring. It did not affect methylation but increased mRNA
      expression of Snrpn, Peg3, Igf2r and Air ncRNA. In muscle and liver, TCDD (10
      ng/kg/day) induced increases in methylation and decreases in mRNA expression of
      Igf2r. These results show that the robust effects of TCDD on the mRNA expression
      of Snrpn, Peg3 and Igf2r genes in the sperm and of Igf2r in the muscle and liver
      are unrelated to changes in methylation in their respective genes.

PMID- 23142539
TI  - Enhanced recovery from ischemia-reperfusion injury in PI3Kalpha dominant negative
      hearts: investigating the role of alternate PI3K isoforms, increased glucose
      oxidation and MAPK signaling.
AB  - Classical ischemia-reperfusion (IR) preconditioning relies on
      phosphatidylinositol 3-kinase (PI3K) for protective signaling. Surprisingly,
      inhibition of PI3Kalpha activity using a dominant negative (DN) strategy
      protected the murine heart from IR injury. It has been proposed that increased
      signaling through PI3Kgamma may contribute to the improved recovery of
      PI3KalphaDN hearts following IR. To investigate the mechanism by which
      PI3KalphaDN hearts are protected from IR injury, we created a double mutant
      (PI3KDM) model by crossing p110gamma(-/-) (PI3KgammaKO) with cardiac-specific
      PI3KalphaDN mice. The PI3KDM model has morphological and hemodynamic features
      that are characteristic of both PI3Kgamma(-/-) and PI3KalphaDN mice.
      Interestingly, when subjected to IR using ex vivo Langendorff perfusion, PI3KDM
      hearts showed significantly enhanced functional recovery when compared to
      wildtype (WT) hearts. However, signaling downstream of PI3K through Akt and
      GSK3beta, which has been associated with IR protection, was reduced in PI3KDM
      hearts. Using ex vivo working heart perfusion, we found no difference in
      functional recovery after IR between PI3KDM and PI3KalphaDN; also, glucose
      oxidation rates were significantly increased in PI3KalphaDN hearts when compared
      to WT, and this metabolic shift has been associated with enhanced IR recovery.
      However, we found that PI3KalphaDN hearts still had enhanced recovery when
      perfused exclusively with fatty acids (FA). We then investigated parallel
      signaling pathways, and found that mitogen-activated protein kinase signaling was
      increased in PI3KalphaDN hearts, possibly through the inhibition of negative
      feedback loops downstream of PI3Kalpha.

PMID- 23142540
TI  - Optical and electrical recordings from isolated coronary-perfused ventricular
      wedge preparations.
AB  - The electrophysiological heterogeneity that exists across the ventricular wall in
      the mammalian heart has long been recognized, but remains an area that is
      incompletely understood. Experimental studies of the mechanisms of
      arrhythmogenesis in the whole heart often examine the epicardial surface in
      isolation and thereby disregard transmural electrophysiology. Significant
      heterogeneity exists in the electrophysiological properties of cardiomyocytes
      isolated from different layers of the ventricular wall, and given that regional
      heterogeneities of membrane repolarization properties can influence the
      electrophysiological substrate for re-entry, the diversity of cell types and
      characteristics spanning the ventricular wall is important in the study of
      arrhythmogenesis. For these reasons, coronary-perfused left ventricular wedge
      preparations have been developed to permit the study of transmural
      electrophysiology in the intact ventricle. Since the first report by Yan and
      Antzelevitch in 1996, electrical recordings from the transmural surface of canine
      wedge preparations have provided a wealth of data regarding the cellular basis
      for the electrocardiogram, the role of transmural heterogeneity in
      arrhythmogenesis, and differences in the response of the different ventricular
      layers to drugs and neurohormones. Use of the wedge preparation has since been
      expanded to other species and more recently it has also been widely used in
      optical mapping studies. The isolated perfused wedge preparation has become an
      important tool in cardiac electrophysiology. In this review, we detail the
      methodology involved in recording both electrical and optical signals from the
      coronary-perfused wedge preparation and review the advances in cardiac
      electrophysiology achieved through study of the wedge.

PMID- 23142541
TI  - TRPV4 channels mediate cardiac fibroblast differentiation by integrating
      mechanical and soluble signals.
AB  - The phenotypic switch underlying the differentiation of cardiac fibroblasts into
      hypersecretory myofibroblasts is critical for cardiac remodeling following
      myocardial infarction. Myofibroblasts facilitate wound repair in the myocardium
      by secreting and organizing extracellular matrix (ECM) during the wound healing
      process. However, the molecular mechanisms involved in myofibroblast
      differentiation are not well known. TGF-beta has been shown to promote
      differentiation and this, combined with the robust mechanical environment in the
      heart, lead us to hypothesize that the mechanotransduction and TGF-beta signaling
      pathways play active roles in the differentiation of cardiac fibroblasts to
      myofibroblasts. Here, we show that the mechanosensitve ion channel TRPV4 is
      required for TGF-beta1-induced differentiation of cardiac fibroblasts into
      myofibroblasts. We found that the TRPV4-specific antagonist AB159908 and siRNA
      knockdown of TRPV4 significantly inhibited TGFbeta1-induced differentiation as
      measured by incorporation of alpha-SMA into stress fibers. Further, we found that
      TGF-beta1-induced myofibroblast differentiation was dependent on ECM stiffness, a
      response that was attenuated by TRPV4 blockade. Finally, TGF-beta1 treated
      fibroblasts exhibited enhanced TRPV4 expression and TRPV4-mediated calcium influx
      compared to untreated controls. Taken together these results suggest for the
      first time that the mechanosensitive ion channel, TRPV4, regulates cardiac
      fibroblast differentiation to myofibroblasts by integrating signals from TGF
      beta1 and mechanical factors.

PMID- 23142542
TI  - Tandem mass spectrometry for measuring stable-isotope labeling.
AB  - Measuring metabolic rates by (13)C-metabolic flux analysis ((13)C-MFA) is of
      central importance for metabolic engineers and biomedical investigators. Enhanced
      knowledge of in vivo fluxes can be applied to reengineer the metabolic,
      regulatory, and phenotypic characteristics of organisms and help uncover the
      mechanisms of human ailments such as cancer and diabetes. To determine accurate
      and precise fluxes by (13)C-MFA advanced methods for measuring stable-isotope
      labeling are needed. The application of tandem mass spectrometry is emerging as a
      new promising technique that has significant advantages over traditional MS and
      NMR based methods. With further refinement, tandem MS has the potential to become
      the new gold standard for measuring isotopic labeling for (13)C-flux studies.

PMID- 23142543
TI  - Tissue engineering on the nanoscale: lessons from the heart.
AB  - Recognizing the limitations of biomaterials for engineering complex tissues and
      the desire for closer recapitulation of the natural matrix have led tissue
      engineers to seek new technologies for fabricating 3-dimensional (3D) cellular
      microenvironments. In this review, through examples from cardiac tissue
      engineering, we describe the nanoscale hallmarks of the extracellular matrix that
      tissue engineers strive to mimic. Furthermore, we discuss the use of inorganic
      nanoparticles and nanodevices for improving and monitoring the performance of
      engineered tissues. Finally, we offer our opinion on the main challenges and
      prospects of applying nanotechnology in tissue engineering. 

PMID- 23142545
TI  - Stable isotope-assisted metabolomics to detect metabolic flux changes in
      mammalian cell cultures.
AB  - The determination of metabolic fluxes provides detailed information of cellular
      physiology, and the assessment of metabolic flux changes upon a certain
      perturbation can help to improve biotechnological and pharmaceutical processes.
      Stable isotope-assisted metabolomics using tracer-labeled substrates is the
      method of choice to determine the fluxes. Though well-established for microbial
      cultures, the application to mammalian cells is generally complex and still
      limited. However, there have been great achievements in recent years and it is
      now emerging that stable isotope-assisted metabolic flux analysis in mammalian
      cell cultures will help improving biotechnological production and will also
      support drug development and discovery.

PMID- 23142546
TI  - Precision of higher-order aberration measurements with a new Placido-disk
      topographer and Hartmann-Shack wavefront sensor.
AB  - PURPOSE: To assess the intrasession and intersession precision of ocular,
      corneal, and internal higher-order aberrations (HOAs) measured using an
      integrated topographer and Hartmann-Shack wavefront sensor (Topcon KR-1W) in
      refractive surgery candidates. SETTING: IOBA-Eye Institute, Valladolid, Spain.
      DESIGN: Evaluation of diagnostic technology. METHODS: To analyze intrasession
      repeatability, 1 experienced examiner measured eyes 9 times successively. To
      study intersession reproducibility, the same clinician obtained measurements from
      another set of eyes in 2 consecutive sessions 1 week apart. Ocular, corneal, and
      internal HOAs were obtained. Coma and spherical aberrations, 3rd- and 4th-order
      aberrations, and total HOAs were calculated for a 6.0 mm pupil diameter. RESULTS:
      For intrasession repeatability (75 eyes), excellent intraclass correlation
      coefficients (ICCs) were obtained (ICC >0.87), except for internal primary coma
      (ICC = 0.75) and 3rd-order (ICC = 0.72) HOAs. Repeatability precision (1.96 *
      S(w)) values ranged from 0.03 MUm (corneal primary spherical) to 0.08 MUm (ocular
      primary coma). For intersession reproducibility (50 eyes), ICCs were good (>0.8)
      for ocular primary spherical, 3rd-order, and total higher-order aberrations;
      reproducibility precision values ranged from 0.06 MUm (corneal primary spherical)
      to 0.21 MUm (internal 3rd order), with internal HOAs having the lowest precision
      (>=0.12 MUm). No systematic bias was found between examinations on different
      days. CONCLUSIONS: The intrasession repeatability was high; therefore, the
      device's ability to measure HOAs in a reliable way was excellent. Under
      intersession reproducibility conditions, dependable corneal primary spherical
      aberrations were provided. FINANCIAL DISCLOSURE: No author has a financial or
      proprietary interest in any material or method mentioned.

PMID- 23142544
TI  - Current algorithmic solutions for peptide-based proteomics data generation and
      identification.
AB  - Peptide-based proteomic data sets are ever increasing in size and complexity.
      These data sets provide computational challenges when attempting to quickly
      analyze spectra and obtain correct protein identifications. Database search and
      de novo algorithms must consider high-resolution MS/MS spectra and alternative
      fragmentation methods. Protein inference is a tricky problem when analyzing large
      data sets of degenerate peptide identifications. Combining multiple algorithms
      for improved peptide identification puts significant strain on computational
      systems when investigating large data sets. This review highlights some of the
      recent developments in peptide and protein identification algorithms for
      analyzing shotgun mass spectrometry data when encountering the aforementioned
      hurdles. Also explored are the roles that analytical pipelines, public spectral
      libraries, and cloud computing play in the evolution of peptide-based proteomics.

PMID- 23142547
TI  - A non-catalytic function of Rev1 in translesion DNA synthesis and mutagenesis is
      mediated by its stable interaction with Rad5.
AB  - DNA damage tolerance consisting of template switching and translesion synthesis
      is a major cellular mechanism in response to unrepaired DNA lesions during
      replication. The Rev1 pathway constitutes the major mechanism of translesion
      synthesis and base damage-induced mutagenesis in model cell systems. Rev1 is a
      dCMP transferase, but additionally plays non-catalytic functions in translesion
      synthesis. Using the yeast model system, we attempted to gain further insights
      into the non-catalytic functions of Rev1. Rev1 stably interacts with Rad5 (a
      central component of the template switching pathway) via the C-terminal region of
      Rev1 and the N-terminal region of Rad5. Supporting functional significance of
      this interaction, both the Rev1 pathway and Rad5 are required for translesion
      synthesis and mutagenesis of 1,N(6)-ethenoadenine. Furthermore, disrupting the
      Rev1-Rad5 interaction by mutating Rev1 did not affect its dCMP transferase, but
      led to inactivation of the Rev1 non-catalytic function in translesion synthesis
      of UV-induced DNA damage. Deletion analysis revealed that the C-terminal 21-amino
      acid sequence of Rev1 is uniquely required for its interaction with Rad5 and is
      essential for its non-catalytic function. Deletion analysis additionally
      implicated a C-terminal region of Rev1 in its negative regulation. These results
      show that a non-catalytic function of Rev1 in translesion synthesis and
      mutagenesis is mediated by its interaction with Rad5.

PMID- 23142548
TI  - Odd RNA polymerases or the A(B)C of eukaryotic transcription.
AB  - Pioneering studies on eukaryotic transcription were undertaken with the bacterial
      system in mind. Will the bacterial paradigm apply to eukaryotes? Are there
      promoter sites scattered in the eukaryotic genome, and sigma-like proteins? Why
      three forms of RNA polymerase in eukaryotic cells? Why are they structurally so
      complex, in particular RNA polymerases I and III, compared to the bacterial
      enzyme? These questions and others that were raised along the way are evoked in
      this short historical survey of odd RNA polymerases studies, with some emphasis
      on the contribution of these studies to our global understanding of eukaryotic
      transcription systems. This article is part of a Special Issue entitled:
      Transcription by Odd Pols.

PMID- 23142549
TI  - Prevalence and molecular characterization of Cryptosporidium in ostriches
      (Struthio camelus) on a farm in central Vietnam.
AB  - This study was performed to determine the prevalence and molecular
      characterization of Cryptosporidium in ostriches on a farm in Khanh Hoa province,
      central Vietnam. A total of 464 ostrich fecal samples were examined
      Cryptosporidium oocysts using the modified Ziehl-Neelsen staining method, and 110
      (overall prevalence 23.7%) were identified as positive by microscopy. Prevalence
      of Cryptosporidium in animals of <45 days, 45-60 days, 61-90 days, 91 days-12
      months and >12 months was 23.5% (16/68), 33.3% (22/66), 35.2% (68/193), 0 and
      5.8% (4/69), respectively (p<0.05). The majority of positive samples scored as
      the 3+ level of intensity of infection were from 61 to 90 days ostriches.
      Molecular analysis in the 18S ribosomal RNA, 70 kDa heat shock protein and actin
      genes demonstrated the presence of only Cryptosporidium avian genotype II in
      ostriches in central Vietnam.

PMID- 23142550
TI  - The effects of cross-hemispheric dorsolateral prefrontal cortex transcranial
      direct current stimulation (tDCS) on task switching.
AB  - BACKGROUND: Task switching, defined as the ability to flexibly switch between
      tasks in the face of goal shifting, is a central mechanism in cognitive control.
      Task switching is thought to involve both prefrontal cortex (PFC) and parietal
      regions. Our previous work has shown that it is possible to modulate set shifting
      tasks using 1 mA tDCS on both the left dorsolateral prefrontal cortex and the
      left primary motor area. However, it remains unclear whether the effects of PFC
      tDCS on task switching are hemisphere-dependent. OBJECTIVES: We aimed to test the
      effects of three types of cross-hemispheric tDCS over the PFC (left anode-right
      cathode [LA-RC], left cathode-right anode [LC-RA] and sham stimulation) on
      participants' performance (reaction time) and accuracy (correct responses) in two
      task-switching paradigms (i.e., letter/digit naming and vowel-consonant/parity
      tasks). METHODS: Sixteen participants received cross-hemispheric tDCS over the
      PFC in two task-switching paradigms. RESULTS: The results show that cross
      hemispheric tDCS over the PFC modulates task-switching ability in both paradigms.
      Our results were task and hemisphere-specific, such that in the letter/digit
      naming task, LA-RC tDCS increased switching performance, whereas LC-RA tDCS
      improved accuracy. On the other hand, in the vowel-consonant/parity task, LA-RC
      improved accuracy, and decreased switching performance. CONCLUSIONS: Our findings
      confirm the notion that involvement of the PFC on task switching depends
      critically on laterality, implying the existence of different roles for the left
      hemisphere and the right hemisphere in task switching.

PMID- 23142551
TI  - Review of the sylvatic cycle of African swine fever in sub-Saharan Africa and the
      Indian ocean.
AB  - African swine fever (ASF) is a major limiting factor for pig production in most
      of the countries in Sub-Saharan Africa and the Indian Ocean. In the absence of
      vaccine, a good understanding of the ecology and epidemiology of the disease is
      fundamental to implement effective control measures. In selected countries of
      Southern and East Africa, the association between Ornithodoros moubata ticks and
      warthogs has been described in detail in the literature. However, for many other
      countries in the region, information related to the sylvatic cycle is lacking or
      incomplete. In West African countries, for instance, the role of wild pigs in the
      epidemiology of ASF has never been demonstrated and the existence and potential
      impact of a sylvatic cycle involving an association between soft ticks and
      warthogs is questionable. In other countries, other wild pig species such as the
      bushpigs (Potamochoerus spp.) can also be asymptomatically infected by the virus
      but their role in the epidemiology of the disease is unclear and might differ
      according to geographic regions. In addition, the methods and techniques required
      to study the role of wild hosts in ASF virus (ASFV) epidemiology and ecology are
      very specific and differ from the more traditional methods to study domestic pigs
      or other tick species. The aim of this review is (i) to provide a descriptive
      list of the methodologies implemented to study the role of wild hosts in African
      swine fever, (ii) to compile the available knowledge about the sylvatic cycle of
      ASFV in different regions of Sub-Saharan Africa and the Indian Ocean in addition
      to the one that has been described for East and Southern Africa, and (iii) to
      discuss current methodologies and available knowledge in order to identify new
      orientations for further field and experimental surveys.

PMID- 23142552
TI  - African swine fever virus eradication in Africa.
AB  - African swine fever was reported in domestic pigs in 26 African countries during
      the period 2009-2011. The virus exists in an ancient sylvatic cycle between
      warthogs (Phacochoerus africanus) and argasid ticks of the Ornithodoros moubata
      complex in many of the countries reporting outbreaks and in two further countries
      in the region. Eradication of the virus from the countries in eastern and
      southern Africa where the classic sylvatic cycle occurs is clearly not an option.
      However, the virus has become endemic in domestic pigs in 20 countries and the
      great majority of outbreaks in recent decades, even in some countries where the
      sylvatic cycle occurs, have been associated with movement of infected pigs and
      pig meat. Pig production and marketing and ASF control in Africa have been
      examined in order to identify risk factors for the maintenance and spread of ASF.
      These include large pig populations, traditional free-range husbandry systems,
      lack of biosecurity in semi-intensive and intensive husbandry systems, lack of
      organisation in both pig production and pig marketing that results in lack of
      incentives for investment in pig farming, and ineffective management of ASF. Most
      of these factors are linked to poverty, yet pigs are recognised as a livestock
      species that can be used to improve livelihoods and contribute significantly to
      food security. The changes needed and how they might be implemented in order to
      reduce the risk of ASF to pig producers in Africa and to the rest of the world
      are explored.

PMID- 23142553
TI  - African swine fever virus replication and genomics.
AB  - African swine fever virus (ASFV) is a large icosahedral DNA virus which
      replicates predominantly in the cytoplasm of infected cells. The ASFV double
      stranded DNA genome varies in length from about 170 to 193 kbp depending on the
      isolate and contains between 150 and 167 open reading frames. These are closely
      spaced and read from both DNA strands. The virus genome termini are covalently
      closed by imperfectly base-paired hairpin loops that are present in two forms
      that are complimentary and inverted with respect to each other. Adjacent to the
      termini are inverted arrays of different tandem repeats. Head to head
      concatemeric genome replication intermediates have been described. A similar
      mechanism of replication to Poxviruses has been proposed for ASFV. Virus genome
      transcription occurs independently of the host RNA polymerase II and virus
      particles contain all of the enzymes and factors required for early gene
      transcription. DNA replication begins in perinuclear factory areas about 6h post
      infection although an earlier stage of nuclear DNA synthesis has been reported.
      The virus genome encodes enzymes required for transcription and replication of
      the virus genome and virion structural proteins. Enzymes that are involved in a
      base excision repair pathway may be an adaptation to enable virus replication in
      the oxidative environment of the macrophage cytoplasm. Other ASFV genes encode
      factors involved in evading host defence systems and modulating host cell
      function. Variation between the genomes of different ASFV isolates is most
      commonly due to gain or loss of members of multigene families, MGFs 100, 110,
      300, 360, 505/530 and family p22. These are located within the left terminal
      40kbp and right terminal 20kbp. ASFV is the only member of the Asfarviridae,
      which is one of the families within the nucleocytoplasmic large DNA virus
      superfamily.

PMID- 23142554
TI  - Inhibition of Japanese encephalitis virus infection in vitro and in vivo by
      pokeweed antiviral protein.
AB  - Pokeweed antiviral protein (PAP) is a plant-derived N-glycosidase ribosomal
      inactivating protein isolated from Phytolacca americana. The antiviral activity
      of PAP has been described in several viruses. This study was to investigate the
      antiviral activity of PAP against Japanese encephalitis virus (JEV) infection in
      vitro and in vivo. Antiviral activity of PAP against JEV infection was evaluated
      in vitro using plaque forming assay, qRT-PCR and Western blot analysis. In vitro
      results showed that PAP inhibited replication of JEV in a dose-dependent manner
      with 50% inhibitory concentration (IC(50)) of 300 ng/ml (23.1 nM). Depurination
      assay suggested that the antiviral activity of PAP against JEV infection might be
      partially due to depurination of JEV genomic RNA. In vivo studies showed that PAP
      (1.0mg/kg) administered intraperitoneally decreased infection in mice challenged
      with a lethal dose of JEV, presenting a survival of 87.5% or 85.7% when
      administered pre-infection or post-infection. Collectively, our studies
      demonstrated that PAP possesses antiviral activity against JEV infection in vitro
      and in vivo, providing evidences for further development of PAP as an antiviral
      agent against JEV infection.

PMID- 23142555
TI  - Traditionally used Veronica officinalis inhibits proinflammatory mediators via
      the NF-kappaB signalling pathway in a human lung cell line.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Extracts from Veronica officinalis L. are
      traditionally used for the treatment of lung diseases; however, the effective
      compounds and the mode of action are still unknown. AIM OF THE STUDY: Here we
      analyzed the effects of a standardized Veronica extract on genes expression and
      signalling protein production associated with the development of inflammatory
      lung diseases. MATERIAL AND METHODS: The degranulation capacity of primary mast
      cells, as well as gene expression and release of inflammatory mediators from
      human lung epithelial cells (A549 cells) were analyzed in relation to the
      synthetic drugs azelastine and dexamethasone. Gene and protein expression of
      cyclooxygenase-2 were investigated by semi-quantitative RT-PCR and western
      blotting, respectively. The involvement of phosphorylated mitogen-activated
      protein kinases and NF-kappaB signaling in regulation of these molecules were
      characterized by western blotting and electrophoretic mobility shift assays.
      Characteristic extract components were identified by LC-MS and verminoside was
      quantified by HPLC analysis. RESULTS: We demonstrated that Veronica officinalis
      has a small influence on the degranulation capacity of mast cells but rather
      inhibits gene and protein expression of the chemokine eotaxin in A549 lung
      epithelial cells, which is essential for recruitment of inflammatory-associated
      cells in lung diseases. Furthermore, release of the inflammatory mediator PGE(2)
      was diminished through inhibition of COX-2 expression via the NF-kappaB signaling
      pathway in TNF-alpha-activated A549 cells. Phytochemical analysis identified
      verproside and verminoside as the most abundant iridoid glycosides. CONCLUSION:
      Our results are a contribution to explaining the observed anti-inflammatory
      effects of Veronica offcinalis extract on a molecular level. However, its
      clinical potency has at first to be proven in animals and subsequently in
      clinical trials.

PMID- 23142556
TI  - The clinical predictive factors for subsequent distant metastasis in patients
      with locoregionally advanced oral squamous cell carcinoma.
AB  - OBJECTIVES: Only a small portion of the patients with locoregionally advanced
      oral squamous cell carcinoma (OSCC) experience subsequent distant metastasis.
      This study is to evaluate the occurrence of distant metastasis after curative
      treatment and to explore the predictive factors for subsequent distant metastasis
      in patients with locoregionally advanced OSCC. MATERIALS AND METHODS: The medical
      records of all patients with locoregionally advanced OSCC without distant
      metastasis at the time of diagnosis (AJCC stage III, IV but not IVC) who
      underwent curative surgery with or without adjuvant radiation between 2004 and
      2009 were retrospectively reviewed. RESULTS: A total of 628 patients were
      enrolled, including 562 male and 66 female patients. The 5-year distant
      metastasis rate was 13.2%. The 5-year disease-free and overall survival rates
      were 57.0% and 60.3%, respectively. Multivariate analyses revealed that poorly
      differentiated tumors (HR=2.3 (1.16-4.53), p=0.02) and contralateral neck
      metastasis (HR=7.55 (3.20-17.83), p<0.001) were independent adverse factors for
      distant metastasis-free survival. The 5-year distant metastasis rates of 447
      patients with well-differentiated tumors, 140 patients with moderately
      differentiated tumors and 41 patients with poorly differentiated tumors were
      12.1%, 18.2%, and 34.1%, respectively. The 5-year distant metastasis rates of 227
      patients without neck metastasis, 350 patients with ipsilateral neck metastasis
      and 51 patients with contralateral neck metastasis were 6.7%, 15.1%, and 55.3%,
      respectively. CONCLUSIONS: Poorly differentiated tumors and contralateral neck
      metastasis were independent factors for subsequent distant metastasis in patients
      with locoregionally advanced OSCC.

PMID- 23142557
TI  - The role of mouthwashes in promoting microbial colonisation during cytotoxic
      therapy.

PMID- 23142558
TI  - The 17-beta-oestradiol inhibits osteoclast activity by increasing the cannabinoid
      CB2 receptor expression.
AB  - Bone is a highly metabolically active tissue and its formation and resorption is
      at the base of bone remodelling. The critical importance of a balanced bone
      remodelling is demonstrated by human diseases, i.e. osteoporosis, in which a net
      increase in bone resorption is responsible of skeleton weakening and fracture
      risk. Oestrogens display anti-resorptive properties on bone metabolism. Indeed,
      the so-called post-menopausal osteoporosis occurs after interruption of gonad
      function and benefits from hormonal replacement treatment. Recently, an important
      role for the endocannabinoid system in the regulation of skeletal remodelling in
      human has also been shown. In particular, we showed that CB2 stimulation is able
      to reduce the number of human OCs in vitro. Here, we provide unprecedented
      evidence that 17-beta-oestradiol administration inhibits activity and formation
      of human OCs in vitro, demonstrating that oestrogens are able to induce an
      increase of CB2 expression probably through the recruitment of a putative
      oestrogens responsive element in the CB2 encoding for gene.

PMID- 23142559
TI  - TNF-alpha-induced CXCL8 production by A549 cells: involvement of the non-neuronal
      cholinergic system.
AB  - It was recently suggested that the non-neuronal cholinergic system has a
      regulatory role in pulmonary inflammation. We investigated this system's
      involvement in the control of cytokine production by the A549 human alveolar
      epithelial cell line. CXCL8 and acetylcholine (ACh) concentrations were measured
      using ELISA and LC-MS/MS, respectively. The mRNA expression of muscarinic
      receptor (MR) subtypes was determined using RT-PCR. In A549 cells, TNF-alpha
      increased the release of CXCL8 and ACh and the expression of the subtype 3 MR
      (M3R). Furthermore, TNF-alpha-induced CXCL8 secretion was (i) inhibited by the MR
      antagonist tiotropium and the M3R antagonist 4-DAMP and (ii) enhanced by the
      M1/M3R agonist pilocarpine and the cholinesterase inhibitor physostigmine. Taken
      as a whole, these results suggest that ACh release by A549 cells enhances TNF
      alpha-induced CXCL8 secretion through activation of the M3R. Western blot
      analysis revealed that pilocarpine and physostigmine enhanced the TNF-alpha
      induced phosphorylation of ERK1/2 and p38 MAPK and the degradation of
      IkappaBalpha. Inhibition of these pathways with specific inhibitors abrogated the
      pilocarpine-induced CXCL8 release. Our results suggest that the TNF-alpha-induced
      secretion of CXCL8 in A549 cells is regulated by the release of ACh, the latter's
      binding to the M3R and the downstream activation of NF-kappaB and the ERK1/2 and
      p38 MAPK signaling pathways. Our findings suggest that MR antagonists may have
      anti-inflammatory effects by preventing pro-inflammatory events driven by
      endogenous, non-neuronal ACh.

PMID- 23142560
TI  - Right ventricular oxygen supply parameters are decreased in human and
      experimental pulmonary hypertension.
AB  - BACKGROUND: In pulmonary arterial hypertension (PAH), high right ventricular (RV)
      power output requires increased myocardial oxygen consumption. Oxygen supply,
      however, does not increase in proportion. It is unknown what cellular mechanisms
      underlie this lack of adaptation. We therefore determined oxygen supply
      parameters in RV tissue slices of deceased PAH patients and compared them with RV
      tissue of patients who died from left ventricular myocardial infarction (MI).
      Because autopsy tissue only reflects end-stage disease, rat models with stable
      and progressive pulmonary hypertension (PH) were studied as well. METHODS:
      Myocardial tissue of 10 PAH and 10 MI patients was collected at autopsy. In rats,
      stable PH (n = 6) and progressive PH (n = 6) was induced by 40 or 60 mg/kg
      monocrotaline, respectively. Six rats were used as controls. RESULTS: RV
      cardiomyocyte cross-sectional area was strongly increased in PAH compared with MI
      patients (p < 0.001), whereas capillary density decreased (p < 0.01). Rat data
      showed similar RV hypertrophy in stable and progressive PH, and RV capillary
      density was decreased in both (p < 0.01 and p < 0.0001 vs control rats,
      respectively). RV myoglobin protein content and functional concentration were
      reduced in both human and rat PH RVs. In rats, this results from a lack of
      increase in myoglobin mRNA transcription per cardiomyocyte nucleus. CONCLUSIONS:
      All measured cellular oxygen supply parameters are decreased in the failing human
      and rat pulmonary hypertensive RV. In contrast to stable PH rats, compensatory
      adaptations do not occur in end-stage PAH, despite higher myocardial oxygen
      consumption.

PMID- 23142561
TI  - Persistent strong anti-HLA antibody at high titer is complement binding and
      associated with increased risk of antibody-mediated rejection in heart transplant
      recipients.
AB  - BACKGROUND: Sensitized heart transplant candidates are evaluated for donor
      specific anti-HLA IgG antibody (DSA) by Luminex single-antigen bead (SAB) testing
      (SAB-IgG) to determine donor suitability and help predict a positive complement
      dependent cytotoxicity crossmatch (CDC-XM) by virtual crossmatching (VXM).
      However, SAB testing used for VXM does not correlate perfectly with CDC-XM
      results and individual transplant programs have center-specific permissible
      thresholds to predict crossmatch positivity. A novel Luminex SAB-based assay
      detecting C1q-binding HLA antibodies (SAB-C1q) contributes functional information
      to SAB testing, but the relationship between SAB strength and complement-binding
      ability is unclear. METHODS: In this retrospective study, we identified 15
      pediatric and adult heart allograft candidates with calculated panel-reactive
      antibody (cPRA) >50% by SAB-IgG and compared conventional SAB-IgG results with
      SAB-C1q testing. RESULTS: Pre- and post-transplant DSA by SAB-C1q correlated with
      DSA by SAB-IgG and also with CDC-XM results and early post-transplant
      endomyocardial biopsy findings. Individual HLA antibodies by SAB-IgG in undiluted
      sera correlated poorly with SAB-C1q; however, when sera were diluted 1:16, SAB
      IgG results were well correlated with SAB-C1q. In some sera, HLA antibodies with
      low mean fluorescent intensity (MFI) by SAB-IgG exhibited high SAB-C1q MFIs for
      the same HLA antigens. Diluting or heat-treating these sera increased SAB-IgG
      MFI, consistent with SAB-C1q results. In 13 recipients, SAB-C1q-positive DSA was
      associated with positive CDC-XM and with early clinical post-transplant antibody
      mediated rejection (cAMR). CONCLUSIONS: Risk assessment for positive CDC-XM and
      early cAMR in sensitized heart allograft recipients are correlated with SAB-C1q
      reactivity.

PMID- 23142562
TI  - Parental restriction and children's diets. The chocolate coin and Easter egg
      experiments.
AB  - Two naturalistic experiments are reported exploring the impact of parental
      restriction on children's diets. For study 1, 53 parents gave 75 g of chocolate
      coins to their child over a weekend. For study 2, 86 parents were recruited prior
      to the 2 week Easter break when their children would be receiving chocolate
      Easter eggs. For both studies, parents were randomly allocated to either the non
      restriction or restriction conditions and rated their child's preoccupation with
      the target food and other sweet foods (demanding and eating) at the start and end
      of the interventions. Perceived and actual food intake was assessed. Children in
      the restriction conditions consumed fewer chocolate coins and Easter eggs. All
      children showed decreased preoccupation with chocolate coins or Easter eggs over
      the course of the studies yet by the end the restriction group were more
      preoccupied with the target food. In contrast, all children showed an increased
      preoccupation with other sweet foods as the studies progressed which was greater
      in the non-restriction group for the chocolate coins study. Overall, restriction
      resulted in reduced intake but relative increased preoccupation with the food
      being restricted. Non-restriction resulted in a greater preoccupation with other
      sweet foods once the target foods had been consumed.

PMID- 23142563
TI  - News report. Gaps and weaknesses in controls on food and drink marketing to
      children in the UK.
AB  - In 2011 the National Heart Forum completed a commission from the UK Department of
      Health to conduct a mapping and consultation exercise on the marketing and
      promotion of food and drinks to children. One of the outputs was an analysis of
      the regulatory environment including statutory and self-regulatory rules and
      voluntary codes of conduct. The key findings and observations from this analysis
      are presented in this short report.

PMID- 23142564
TI  - Healthy dining. Subtle diet reminders at the point of purchase increase low
      calorie food choices among both chronic and current dieters.
AB  - There is a growing consensus that our food-rich living environment contributes to
      rising numbers of people with overweight and obesity. Low-cost, effective
      intervention tools are needed to facilitate healthy eating behavior, especially
      when eating away from home. Therefore, we present a field experiment in a
      restaurant that tested whether providing subtle environmental diet reminders
      increases low-calorie food choices among both chronic and current dieters. For
      half of the participants, the menu was supplemented with diet-related words, as
      reminders of healthy eating and dieting. We recorded customers' choices of low
      calorie or high-calorie items from the menu, and we assessed chronic and current
      dieting. Consistent with our hypotheses, we found that diet reminders increased
      choices for low-calorie foods, among both chronic and current dieters. After a
      diet reminder, around half of dieters made a healthy menu choice. This study
      demonstrates the efficacy of providing subtle diet reminders as a low-cost
      practical intervention to increase low-calorie food choices among weight
      concerned individuals, who are motivated to regulate their eating behavior but
      have been found to often fail in food-rich environments.

PMID- 23142565
TI  - Fluorone dyes have binding sites on both cytoplasmic and extracellular domains of
      Na,K-ATPase.
AB  - Combination of fluorescence techniques and molecular docking was used to monitor
      interaction of Na,K-ATPase and its large cytoplasmic loop connecting fourth and
      fifth transmembrane helices (C45) with fluorone dyes (i.e. eosin Y, 5(6)
      carboxyeosin, rose bengal, fluorescein, and erythrosine B). Our data suggested
      that there are at least two binding sites for all used fluorone dyes, except of
      5(6)-carboxyeosin. The first binding site is located on C45 loop, and it is
      sensitive to the presence of nucleotide. The other site is located on the
      extracellular part of the enzyme, and it is sensitive to the presence of Na(+) or
      K(+) ions. The molecular docking revealed that in the open conformation of C45
      loop (which is obtained in the presence of ATP) all used fluorone dyes occupy
      position directly inside the ATP-binding pocket, while in the closed conformation
      (i.e. in the absence of any ligand) they are located only near the ATP-binding
      site depending on their different sizes. On the extracellular part of the
      protein, the molecular docking predicts two possible binding sites with similar
      binding energy near Asp897(alpha) or Gln69(beta). The former was identified as a
      part of interaction site between alpha- and beta-subunits, the latter is in
      contact with conserved FXYD sequence of the gamma-subunit. Our findings provide
      structural explanation for numerous older studies, which were performed with
      fluorone dyes before the high-resolution structures were known. Further, fluorone
      dyes seem to be good probes for monitoring of intersubunit interactions
      influenced by Na(+) and K(+) binding.

PMID- 23142566
TI  - Plantaricin A, a cationic peptide produced by Lactobacillus plantarum,
      permeabilizes eukaryotic cell membranes by a mechanism dependent on negative
      surface charge linked to glycosylated membrane proteins.
AB  - Lactobacillus plantarum C11 releases plantaricin A (PlnA), a cationic peptide
      pheromone that has a membrane-permeabilizing, antimicrobial effect. We have
      previously shown that PlnA may also permeabilize eukaryotic cells, with a potency
      that differs between cell types. It is generally assumed that cationic
      antimicrobial peptides exert their effects through electrostatic attraction to
      negatively charged phospholipids in the membrane. The aim of the present study
      was to investigate if removal of the negative charge linked to glycosylated
      proteins at the cell surface reduces the permeabilizing potency of PlnA. The
      effects of PlnA were tested on clonal rat anterior pituitary cells (GH(4) cells)
      using patch clamp and microfluorometric techniques. In physiological
      extracellular solution, GH(4) cells are highly sensitive to PlnA, but the
      sensitivity was dramatically reduced in solutions that partly neutralize the
      negative surface charge of the cells, in agreement with the notion that
      electrostatic interactions are probably important for the PlnA effects.
      Trypsination of cells prior to PlnA exposure also rendered the cells less
      sensitive to the peptide, suggesting that negative charges linked to membrane
      proteins are involved in the permeabilizing action. Finally, pre-exposure of
      cells to a mixture of enzymes that split carbohydrate residues from the backbone
      of glycosylated proteins also impeded the PlnA-induced membrane permeabilization.
      We conclude that electrostatic attraction between PlnA and glycosylated membrane
      proteins is probably an essential first step before PlnA can interact with
      membrane phospholipids. Deviating glycosylation patterns may contribute to the
      variation in PlnA sensitivity of different cell types, including cancerous cells
      and their normal counterparts.

PMID- 23142569
TI  - Maternal familism predicts birthweight and asthma symptoms three years later.
AB  - There are marked ethnic and socioeconomic differences in birthweight and
      childhood asthma, conditions which may be linked causally or via a third
      variable. Cultural resources are often credited with diminished health
      disparities in infancy and childhood among subsets of poor and minority
      populations; yet direct empirical tests of this hypothesis are needed. In this
      study, ethnicity, lifespan family socioeconomic position (FSEP), and the cultural
      resource of familism were compared as predictors of birthweight and expression of
      asthma symptoms (AE) by age three. Familism and lifespan FSEP were assessed in
      4633 socioeconomically disadvantaged African Americans, White Americans, and
      Latinas upon giving birth, as was offspring birthweight. AE was assessed in
      offspring through age three. Asthma diagnosis by age three was likelier in very
      low (<= 1500 g) and low (<= 2500 g) birthweight infants compared to infants born
      at average (2501-3999 g) or larger (>= 4000 g) birthweights. Asthma risk
      associated with lower birthweight was higher for Latinos (17-35%) and African
      Americans (19-23%) than for White Americans (13-14%). As predicted, maternal
      familism was higher among White Americans than among African Americans and
      Latinas, an effect that was largely driven by ethnic disparities in lifespan
      FSEP. Familism predicted continuous birthweight (p = .003) and AE (p = .001) by
      age three independently of ethnicity and lifespan FSEP accounting for appropriate
      control variables, including maternal biomedical risk, maternal acculturation,
      parental marital status, and infant sex. There was a 71-g gain in birthweight for
      every one-unit increase in familism. The protective effect of familism on AE by
      age three was strongest for participants of lower lifespan FSEP. Maternal
      familism is one cultural resource that may reduce reproductive and
      intergenerational health disparities in both U.S.- and foreign-born Americans.
      Consistent with our previous work, familism and other nonmaterial resources
      covary with material resources. Nevertheless, culture is distinguishable from
      lifespan FSEP and ethnicity, and has health implications beyond associations to
      ethnicity, lifespan FSEP, and related biomedical and sociodemographic factors.

PMID- 23142567
TI  - Structural and functional analysis of the natural JNK1 inhibitor quercetagetin.
AB  - c-Jun NH2-terminal kinases (JNKs) and phosphatidylinositol 3-kinase (PI3-K) play
      critical roles in chronic diseases such as cancer, type II diabetes, and obesity.
      We describe here the binding of quercetagetin (3,3',4',5,6,7-hydroxyflavone),
      related flavonoids, and SP600125 to JNK1 and PI3-K by ATP-competitive and
      immobilized metal ion affinity-based fluorescence polarization assays and measure
      the effect of quercetagetin on JNK1 and PI3-K activities. Quercetagetin
      attenuated the phosphorylation of c-Jun and AKT, suppressed AP-1 and NF-kappaB
      promoter activities, and also reduced cell transformation. It attenuated tumor
      incidence and reduced tumor volumes in a two-stage skin carcinogenesis mouse
      model. Our crystallographic structure determination data show that quercetagetin
      binds to the ATP-binding site of JNK1. Notably, the interaction between Lys55,
      Asp169, and Glu73 of JNK1 and the catechol moiety of quercetagetin reorients the
      N-terminal lobe of JNK1, thereby improving compatibility of the ligand with its
      binding site. The results of a theoretical docking study suggest a binding mode
      of PI3-K with the hydroxyl groups of the catechol moiety forming hydrogen bonds
      with the side chains of Asp964 and Asp841 in the p110gamma catalytic subunit.
      These interactions could contribute to the high inhibitory activity of
      quercetagetin against PI3-K. Our study suggests the potential use of
      quercetagetin in the prevention or therapy of cancer and other chronic diseases.

PMID- 23142570
TI  - Anti-Trichomonas vaginalis activity of Hypericum polyanthemum extract obtained by
      supercritical fluid extraction and isolated compounds.
AB  - The anti-Trichomonas vaginalis activity of Hypericum polyanthemum extract
      obtained by supercritical fluid extraction (50 degrees C, 150bar) and the
      chemical compounds isolated and purified from this extract (benzopyrans HP1, HP2,
      HP3, and phloroglucinol derivative uliginosin B) were assessed. All samples had
      anti-T. vaginalis activity; however, HP1 demonstrated the best selectivity
      against this protozoan (metronidazole-resistant and susceptible isolates), with
      no cytotoxicity on mammalian cells (selectivity index of 73.97). Moreover, HP1
      had activity against a metronidazole-resistant isolate (52% of viable
      trophozoites), and this effect was higher when tested with a low concentration of
      metronidazole (23% of viable trophozoites). Experiments demonstrated that all
      isolated compounds caused damage to the parasites' membrane (>90% of LDH release)
      and do not present a notable hemolytic effect, although HP2 and uliginosin B
      exhibited cytotoxicity against mammalian cells. Therefore, the analyzed molecules
      are promising prototypes for new antiprotozoal drugs, especially HP1, which seems
      to improve metronidazole's effect on a resistant T. vaginalis isolate.

PMID- 23142571
TI  - Cloning, characterization and validation of inosine 5'-monophosphate
      dehydrogenase of Babesia gibsoni as molecular drug target.
AB  - The inosine monophosphate dehydrogenase (IMPDH) enzyme has been characterized and
      validated as a molecular drug target in other apicomplexans but not in the genus
      Babesia. Subsequently, we cloned and expressed a Babesia gibsoni IMPDH (BgIMPDH)
      cDNA in Escherichia coli. We also determined the inhibitory effect of
      mycophenolic acid (MPA) on recombinant BgIMPDH (rBgIMPDH) activity and the
      Babesia-growths in vitro. The translated BgIMPDH peptide contained thirteen amino
      acid residues responsible for substrate and cofactor binding in its catalytic
      domain with Gly374 in BgIMPDH being replaced by Ser388 in mammalian IMPDH. The
      native BgIMPDH enzyme in the parasite was approximately 54-kDa a mass similar to
      His-tag rBgIMPDH protein. The Km values of the rBgIMPDH were 8.18+/-0.878 (mean+/
      standard error of the mean) MUM and 360.80+/-43.41MUM for IMP and NAD(+),
      respectively. MPA inhibited the rBgIMPDH activity yielding a Ki value of 20.93+/
      1.83MUM with respect to NAD(+). For Babesia growths, the IC50s were 0.95+/-0.21
      and 2.88+/-0.49MUM for B. gibsoni and B. bovis, respectively. Therefore, our
      results suggest that MPA may inhibit the replication of Babesia parasites by
      targeting IMPDH enzyme of the purine pathway.

PMID- 23142572
TI  - Development of immunoblotting techniques for DNA radical detection.
AB  - Radical damage to DNA has been implicated in cell death, cellular dysfunction,
      and cancer. A recently developed method for detecting DNA radicals uses the
      nitrone spin trap DMPO (5,5-dimethyl-1-pyrroline N-oxide) to trap radicals. The
      trapped radicals then decay into stable nitrone adducts detectable with anti-DMPO
      antibodies and quantifiable by ELISA or dot-blot assay. However, the sequences of
      DNA that are damaged are likely to be as important as the total level of damage.
      Therefore, we have developed immunoblotting methods for detection of DNA nitrone
      adducts on electrophoretically separated DNA, comparable to Western blotting for
      proteins. These new techniques not only allow the assessment of relative radical
      adduct levels, but can reveal specific DNA fragments, and ultimately nucleotides,
      as radical targets. Moreover, we have determined that denaturation of samples
      into single-stranded DNA enhances the detection of DNA-DMPO adducts in our new
      blotting methods and also in ELISA.

PMID- 23142573
TI  - Ribosomes - structure and function.

PMID- 23142575
TI  - Catalysis and regulation.

PMID- 23142574
TI  - Unraveling the dynamics of ribosome translocation.
AB  - Translocation is one of the key events in translation, requiring large-scale
      conformational changes in the ribosome, movements of two transfer RNAs (tRNAs)
      across a distance of more than 20A, and the coupled movement of the messenger RNA
      (mRNA) by one codon, completing one cycle of peptide-chain elongation.
      Translocation is catalyzed by elongation factor G (EF-G in bacteria), which
      hydrolyzes GTP in the process. However, how the conformational rearrangements of
      the ribosome actually drive the movements of the tRNAs and how EF-G GTP
      hydrolysis plays a role in this process are still unclear. Fluorescence methods,
      both single-molecule and bulk, have provided a dynamic view of translocation,
      allowing us to follow the different conformational changes of the ribosome in
      real-time. The application of electron microscopy has revealed new conformational
      intermediates during translocation and important structural rearrangements in the
      ribosome that drive tRNA movement, while computational approaches have added
      quantitative views of the translational pathway. These recent advances shed light
      on the process of translocation, providing insight on how to resolve the
      different descriptions of translocation in the current literature.

PMID- 23142576
TI  - Role of the jelly-roll fold in substrate binding by 2-oxoglutarate oxygenases.
AB  - 2-Oxoglutarate (2OG) and ferrous iron dependent oxygenases catalyze two-electron
      oxidations of a range of small and large molecule substrates, including
      proteins/peptides/amino acids, nucleic acids/bases, and lipids, as well as
      natural products including antibiotics and signaling molecules. 2OG oxygenases
      employ variations of a core double-stranded beta-helix (DSBH; a.k.a. jelly-roll,
      cupin or jumonji C (JmjC)) fold to enable binding of Fe(II) and 2OG in a
      subfamily conserved manner. The topology of the DSBH limits regions directly
      involved in substrate binding: commonly the first, second and eighth strands,
      loops between the second/third and fourth/fifth DSBH strands, and the N-terminal
      and C-terminal regions are involved in primary substrate, co-substrate and
      cofactor binding. Insights into substrate recognition by 2OG oxygenases will help
      to enable selective inhibition and bioengineering studies.

PMID- 23142577
TI  - Use of high content image analyses to detect chemical-mediated effects on neurite
      sub-populations in primary rat cortical neurons.
AB  - Traditional developmental neurotoxicity tests performed in vivo are costly, time
      consuming and utilize a large number of animals. In order to address these
      inefficiencies, in vitro models of neuronal development have been used in a first
      tier screening approach for developmental neurotoxicity hazard identification.
      One commonly used endpoint for assessing developmental neurotoxicity in vitro is
      measurement of neurite outgrowth. This biological process is amenable to high
      throughput measurement using high content imaging (HCI) based methodologies. To
      date, a majority of HCI studies of neurite outgrowth have focused on measurements
      of total neurite outgrowth without examining whether stereotypic neuronal growth
      patterns are disrupted or whether specific sub-populations of neurites (i.e.
      axons or dendrites) are selectively affected. The present study describes the
      development and implementation of two HCI based analysis methods for assessing
      chemical effects on neuronal maturation. These methods utilize the stereotypical
      growth pattern of primary rat cortical neurons in culture (i.e. the Staging
      Method), as well as the differential cytoplasmic distribution of beta(III)
      tubulin and MAP2 (i.e. the Subtraction Method), to quantify inhibition of neurite
      initiation, axon outgrowth and secondary neurite (or dendrite) outgrowth in
      response to chemical exposure. Results demonstrate that these distinct
      maturational processes are differentially affected by pharmacological compounds
      (K252a, Na(3)VO(4), Bis-1) known to inhibit neurite outgrowth. Furthermore, a
      group of known developmental neurotoxicants also differentially affected the
      growth of axons and secondary neurites in primary cortical culture. This work
      improves upon previous HCI methods by providing a means in which to rapidly and
      specifically quantify chemical effects on the growth of axons and dendrites in
      vitro.

PMID- 23142578
TI  - Ultrasound-based molecular imaging and specific gene delivery to mesenteric
      vasculature by endothelial adhesion molecule targeted microbubbles in a mouse
      model of Crohn's disease.
AB  - Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal
      tract (GI) for which treatments with immunosuppressive drugs have significant
      side-effects. Consequently, there is a clinical need for site-specific and non
      toxic delivery of therapeutic genes or drugs for CD and related disorders such as
      inflammatory bowel disease. The aim of this study was to validate a gene delivery
      platform based on ultrasound-activated lipid-shelled microbubbles (MBs) targeted
      to inflamed mesenteric endothelium in the CD-like TNFDeltaARE mouse model. MBs
      bearing luciferase plasmid were functionalized with antibodies to MAdCAM-1 (MB-M)
      or VCAM-1 (MB-V), biomarkers of gut endothelial cell inflammation and evaluated
      in an in vitro flow chamber assay with appropriate ligands to confirm targeting
      specificity. Following MB retro-orbital injection in TNFDeltaARE mice, the mean
      contrast intensity in the ileocecal region from accumulated MB-M and MB-V was 8.5
      fold and 3.6-fold greater, respectively, compared to MB-C. Delivery of luciferase
      plasmid to the GI tract in TNFDeltaARE mice was achieved by insonating the
      endothelial cell-bound agents using a commercial sonoporator. Luciferase
      expression in the midgut was detected 48 h later by bioluminescence imaging and
      further confirmed by immunohistochemical staining. The liver, spleen, heart, and
      kidney had no detectable bioluminescence following insonation. Transfection of
      the microcirculation guided by a targeted, acoustically-activated platform such
      as an ultrasound contrast agent microbubble has the potential to be a minimally
      invasive treatment strategy to ameliorate CD and other inflammatory conditions.

PMID- 23142579
TI  - Synthesis and characterization of a stimulus-responsive L-ornithine-degrading
      hydrogel.
AB  - Hydrogels provide a highly favorable matrix for immobilizing growth factors,
      enzymes or cells for biomedical applications like tissue engineering, drug
      delivery or the treatment of metabolic diseases. In this study we describe the
      synthesis and characterization of a hydrogel able to degrade L-ornithine, a
      metabolite that is highly elevated in congenital hyperornithinemia. The hydrogel
      was synthesized by embedding the L-ornithine-degrading enzymes L-ornithine
      aminotransferase (OAT) and L-ornithine decarboxylase (ODC) into a polymer
      network. The network was formed from linear polyacrylamide crosslinked by
      heterodimers of ODC and ornithine decarboxylase antizyme (OAz). The resulting
      hydrogel was shown to be stable under physiological conditions and to efficiently
      degrade L-ornithine. The hydrogel-stabilizing ODC-OAz interactions could
      subsequently be dissociated by the addition of antizyme inhibitor (AzI) which
      resulted in the inducible dissolution of the hydrogel. This L-ornithine-degrading
      hydrogel that can efficiently be eliminated when its functionality is no longer
      required might represent a first step towards an enzyme substitution approach
      against hyperornithinemia.

PMID- 23142580
TI  - CCN2/CTGF binds to fibroblast growth factor receptor 2 and modulates its
      signaling.
AB  - CCN2 plays a critical role in the development of mesenchymal tissues such as
      cartilage and bone, and the binding of CCN2 to various cytokines and receptors
      regulates their signaling.By screening a protein array, we found that CCN2 could
      bind to fibroblast growth factor receptors (FGFRs) 2 and 3, with a higher
      affinity toward FGFR2.We ascertained that FGFR2 bound to CCN2 and that the
      binding of FGFR2 to FGF2 and FGF4 was enhanced by CCN2.CCN2 and FGF2 had a
      collaborative effect on the phosphorylation of ERK and the differentiation of
      osteoblastic cells.The present results indicate the biological significance of
      the binding of CCN2 to FGFR2 in bone metabolism.

PMID- 23142581
TI  - ANKHD1 regulates cell cycle progression and proliferation in multiple myeloma
      cells.
AB  - ANKHD1 is a multiple ankyrin repeat containing protein, highly expressed in
      cancers, such as acute leukemia. The present study was undertaken to determine
      the expression and functional significance of ANKHD1 in human Multiple Myeloma
      (MM). We found that ANKHD1 is highly expressed in MM patient cells and cell
      lines. In vitro, lentiviral mediated ANKHD1-shRNA inhibited proliferation and
      delayed S to G2M cell cycle progression in glucocorticoid resistant (U266) and
      sensitive (MM1S) MM cells. Further ANKHD1 silencing resulted in upregulation of
      cyclin dependent kinase inhibitor p21 irrespective of the p53 status of the MM
      cell lines. These data suggest that ANKHD1 might have a role in MM cell
      proliferation and cell cycle progression by regulating expression of p21.

PMID- 23142582
TI  - Association analysis of toll-like receptor 4 polymorphisms in Japanese primary
      biliary cirrhosis.
AB  - Primary biliary cirrhosis (PBC) is characterized by portal inflammation and
      immune-mediated destruction of intrahepatic bile ducts that often result in liver
      failure. Toll-like receptor (TLR) 4 recognizes lipopolysaccharides of Gram
      negative bacteria. Infectious agents have been suspected to play a crucial role
      in PBC pathogenesis since TLR4 expression was found in bile duct epithelial cells
      and periportal hepatocytes in liver tissues of PBC. To assess the potential
      contribution of TLR4 SNPs to the development of this disease, we genotyped five
      SNPs in TLR4 in 261 PBC patients and 359 controls using a TaqMan assay. No
      significant positive associations with either PBC susceptibility or progression
      were uncovered. These results indicate that TLR4 polymorphisms do not play a
      prominent role in the development of PBC in Japanese patients.

PMID- 23142583
TI  - Single-molecule super-resolution imaging in bacteria.
AB  - Bacteria have evolved complex, multi-component cellular machineries to carry out
      fundamental cellular processes such as cell division/separation, locomotion,
      protein secretion, DNA transcription/replication, or conjugation/competence.
      Diffraction of light has so far restricted the use of conventional fluorescence
      microscopy to reveal the composition, internal architecture and dynamics of these
      important machineries. This review describes some of the more recent advances on
      single-molecule super-resolution microscopy methods applied to bacteria and
      highlights their application to chemotaxis, cell division, DNA segregation, and
      DNA transcription machineries. Finally, we discuss some of the lessons learned
      from this approach, and future perspectives.

PMID- 23142584
TI  - Chemosensory signaling controls motility and subcellular polarity in Myxococcus
      xanthus.
AB  - Myxococcus xanthus is a model system for the study of dynamic protein
      localization and cell polarity in bacteria. M. xanthus cells are motile on solid
      surfaces enabled by two forms of motility. Motility is controlled by the Che-like
      Frz pathway, which is essential for fruiting body formation and differentiation.
      The Frz signal is mediated by a GTPase/GAP protein pair that establishes cell
      polarity and directs the motility systems. Pilus driven motility at the leading
      pole of the cell requires dynamic localization of two ATPases and the coordinated
      production of EPS synthesis. Gliding motility requires dynamic movement of large
      protein complexes, but the mechanism by which this system generates propulsive
      force is still an active area of investigation.

PMID- 23142585
TI  - Evaluation of the quality of information on the Internet available to patients
      undergoing cervical spine surgery.
AB  - OBJECTIVE: To evaluate the quality of information available on the Internet to
      patients with a cervical pathology undergoing elective cervical spine surgery.
      METHODS: Six key words ("cervical discectomy," "cervical foraminotomy," "cervical
      fusion," "cervical disc replacement," "cervical arthroplasty," "cervical
      artificial disc") were entered into two different search engines (Google,
      Yahoo!). For each key word, the first 50 websites were evaluated for
      accessibility, comprehensibility, and website quality using the DISCERN tool,
      transparency and honesty criteria, and an accuracy and exhaustivity scale.
      RESULTS: Of 5,098,500 evaluable websites, 600 were visited; 97 (16%) of these
      websites were evaluated for quality and comprehensiveness. Overall, 3% of sites
      obtained an excellent global quality score, 7% obtained a good score, 25%
      obtained an above average score, 15% obtained an average score, 37% obtained a
      poor score, and 13% obtained a very poor score. High-quality websites were
      affiliated with a professional society (P = 0.021), had bibliographical
      references (P = 0.030), and had a recent update within 6 months (r = 0.277, P <
      0.001). No correlation between global quality score and other variables was
      observed. CONCLUSIONS: This study shows that the search for medical information
      on the Internet is time-consuming and often disappointing. The Internet is a
      potentially misleading source of information. Surgeons and professional societies
      must use the Internet as an ally in providing optimal information to patients.

PMID- 23142586
TI  - Development of intracranial hypertension after surgical management of
      intracranial arachnoid cyst: report of three cases and review of the literature.
AB  - OBJECTIVE: To describe three cases of delayed development of intracranial
      hypertension (IH) after surgical treatment of intracranial arachnoid cyst,
      including the pathogenesis of IH and a review of the literature. METHODS: A
      retrospective and prospective analysis of three male patients (two 18 years old
      and one 45 years old) was performed. All patients underwent surgical intervention
      for symptomatic intracranial arachnoid cyst in the form of fenestration of the
      cyst and a cystoperitoneal shunt. RESULTS: All three patients presented at a
      later stage with new-onset headaches after the initial management of arachnoid
      cyst. Magnetic resonance imaging and magnetic resonance venography ruled out any
      intracranial vascular pathology. Lumbar puncture and intracranial pressure
      monitoring showed increased intracranial pressure suggestive of idiopathic IH. To
      manage IH, intracranial pressure monitoring, cystoperitoneal shunt,
      ventriculoperitoneal shunt, and lumboperitoneal shunt were performed.
      CONCLUSIONS: The pathogenesis of delayed development of IH in this clinical
      setting is not clearly elucidated. When intracranial arachnoid cysts are treated,
      the possibility of future development of IH should be borne in mind. Delayed
      presentation with headaches in patients after treatment of intracranial arachnoid
      cysts should raise the possibility of IH.

PMID- 23142587
TI  - Production of human antimicrobial peptide LL-37 in Escherichia coli using a
      thioredoxin-SUMO dual fusion system.
AB  - LL-37 is a human antimicrobial peptide that has been shown to possess multiple
      functions in host defense. In this report, the peptide was expressed as a fusion
      with a thioredoxin-SUMO dual-tag. Upon SUMO protease mediated cleavage at the
      SUMO/peptide junction, LL-37 with its native N-terminus was generated. The
      released peptide was separated from the dual-tag and cleavage enzyme by size
      exclusion chromatography. Mass spectrometry analysis proves that the recombinant
      peptide has a molecular weight as theoretically expected for its native form. The
      produced peptide displayed antimicrobial activity against Escherichia coli K-12.
      On average, 2.4 mg peptide was obtained from one liter of bacterial culture.
      Thus, the described approach provides an effective alternative for producing
      active recombinant LL-37 with its natural amino acid sequence in E. coli.

PMID- 23142588
TI  - Developing plant-based vaccines against neglected tropical diseases: where are
      we?
AB  - Neglected tropical diseases (NTDs) impair the lives of 1 billion people
      worldwide, and threaten the health of millions more. Although vaccine candidates
      have been proposed to prevent some NTDs, no vaccine is available at the market
      yet. Vaccines against NTDs should be low-cost and needle-free to reduce the
      logistic cost of their administration. Plant-based vaccines meet both
      requirements: plant systems allow antigen production at low cost, and also yield
      an optimal delivery vehicle that prevents or delays digestive hydrolysis of
      vaccine antigens. This review covers recent reports on the development of plant
      based vaccines against NTDs. Efforts conducted by a number of research groups to
      develop vaccines as a mean to fight rabies, cysticercosis, dengue, and
      helminthiasis are emphasized. Future perspectives are identified, such as the
      need to develop vaccination models for more than ten pathologies through a plant
      based biotechnological approach. Current limitations on the method are also
      noted, and molecular approaches that might allow us to address such limitations
      are discussed.

PMID- 23142589
TI  - Virus-like particles as a highly efficient vaccine platform: diversity of targets
      and production systems and advances in clinical development.
AB  - Virus-like particles (VLPs) are a class of subunit vaccines that differentiate
      themselves from soluble recombinant antigens by stronger protective
      immunogenicity associated with the VLP structure. Like parental viruses, VLPs can
      be either non-enveloped or enveloped, and they can form following expression of
      one or several viral structural proteins in a recombinant heterologous system.
      Depending on the complexity of the VLP, it can be produced in either a
      prokaryotic or eukaryotic expression system using target-encoding recombinant
      vectors, or in some cases can be assembled in cell-free conditions. To date, a
      wide variety of VLP-based candidate vaccines targeting various viral, bacterial,
      parasitic and fungal pathogens, as well as non-infectious diseases, have been
      produced in different expression systems. Some VLPs have entered clinical
      development and a few have been licensed and commercialized. This article reviews
      VLP-based vaccines produced in different systems, their immunogenicity in animal
      models and their status in clinical development.

PMID- 23142590
TI  - Chemosensitivity in ovarian metastases from gastric cancer: a case series.
AB  - The development of ovarian metastases from gastric cancer indicates a turning
      point of the disease progression and is usually associated with poor prognosis.
      Efficacy of modern chemotherapy protocols in ovarian metastases from gastric
      cancer is unknown. In this case series, we have evaluated the chemosensitivity of
      ovarian metastases from gastric cancer in eight consecutive patients treated in
      our institution between January 2000 and April 2012. Median age at gastric cancer
      diagnosis was 48.3 years and ovarian metastases were mainly metachronous (88%).
      Patients were treated with FOLFOX or FOLFIRI protocols in first-line and with EOX
      protocol in second-line chemotherapy. These protocols of chemotherapy used in
      first- and second-line treatment were able to control the disease in 33.3% for
      ovarian metastases compared to 66.7% for extraovarian metastases. Mean overall
      survival (OS) from ovarian metastases diagnosis was 14.2 months. The four
      patients treated by bilateral oophorectomy had a longer mean OS (16 months) than
      the four patients who did not experienced surgery (12.3 months). In conclusion,
      this case series suggests that ovarian metastases from gastric cancer are less
      sensitive than extraovarian metastases to modern protocol of chemotherapy. To
      confirm these observations, a large retrospective study is ongoing.

PMID- 23142591
TI  - NR1H4 analysis in patients with progressive familial intrahepatic cholestasis,
      drug-induced cholestasis or intrahepatic cholestasis of pregnancy unrelated to
      ATP8B1, ABCB11 and ABCB4 mutations.
AB  - Farnesoid X receptor (FXR, NR1H4) controls bile acid homeostasis. NR1H4 variants
      may predispose to intrahepatic cholestasis of pregnancy (ICP). We report on NR1H4
      analysis in eight patients with progressive familial intrahepatic cholestasis
      (PFIC) and in eight women with either ICP and/or drug-induced cholestasis (DIC)
      in whom no disease causing mutation in ATP8B1, ABCB11 and/or ABCB4 were found. No
      NR1H4 mutation was found in PFIC patients. In one woman with ICP/DIC, a NR1H4
      heterozygous variant (c.-1G>T) was found. This suggests that a NR1H4 mutation is
      not or rarely involved in hepatocellular cholestasis of unknown cause.

PMID- 23142592
TI  - The role of positive feedback loops involving anti-dsDNA and anti-anti-dsDNA
      antibodies in autoimmune glomerulonephritis.
AB  - Autoimmune glomerulonephritis (GN) is a potentially life-threatening renal
      inflammation occurring in a significant percentage of systemic lupus
      erythematosus (SLE) patients. It has been suggested that GN develops and persists
      due to a positive feedback loop, in which inflammation is promoted by the
      deposition in the kidney of immune complexes (IC) containing double-stranded DNA
      (dsDNA) and autoantibodies specific to it, leading to cellular death, additional
      release to circulation of dsDNA, continuous activation of dsDNA-specific
      autoreactive B cells and further formation of IC. We have recently presented a
      generic model exploring the dynamics of IC-mediated autoimmune inflammatory
      diseases, applicable also to GN. Here we extend this model by incorporating into
      it a specific B cell response targeting anti-dsDNA antibodies-a phenomenon whose
      occurrence in SLE patients is well-supported empirically. We show that this model
      retains the main results found for the original model studied, particularly with
      regard to the sensitivity of the steady state properties to changes in parameter
      values, while capturing some disease-specific observations found in GN patients
      which are unaccountable using our previous model. In particular, the extended
      model explains the findings that this inflammation can be ameliorated by
      treatment without lowering the level of anti-dsDNA antibodies. Moreover, it can
      account for the inverse oscillations of anti-dsDNA and anti-anti-dsDNA
      antibodies, previously reported in lupus patients. Finally, it can be used to
      suggest a possible explanation to the so-called regulatory role of TLR9, found in
      murine models of lupus; i.e., the fact that the knockdown of this DNA-sensing
      receptor leads, as expected, to a decrease in the level of anti-dsDNA antibodies,
      but at the same time results in a counter-intuitive amplification of the
      autoreactive immune response and an exacerbated inflammation. Several predictions
      can be derived from the analysis of the presented model, allowing its
      experimental verification.

PMID- 23142593
TI  - Secretion of ATP from Schwann cells through lysosomal exocytosis during Wallerian
      degeneration.
AB  - The present study demonstrates that adenosine triphosphate (ATP) is released from
      Schwann cells through lysosomal exocytosis during Wallerian degeneration and in
      response to stimulation. In primary Schwann cell cultures, ATP was stored in
      lysosomal vesicles. ATP could then induce Ca(2+)-dependent lysosomal exocytosis.
      Among three stimulants of lysosomal exocytosis (glutamate, NH(4)Cl and zymosan),
      only NH(4)Cl was sufficient to induce ATP release from ex vivo sciatic nerve
      explants at 3 days in vitro. Lysosomal exocytosis inhibitors (metformin,
      chlorpromazine and vacuolin-1) reversed the effect of NH(4)Cl-enhanced ATP
      release, replicating the state of explants treated with NH(4)Cl in the absence of
      lysosomal exocytosis inhibitors. Furthermore, we observed ATP release through
      lysosomal exocytosis during Wallerian degeneration in sciatic explant cultures
      using the recently identified vesicular nucleotide transporter (VNUT). From these
      experiments, we conclude that the exocytosis of lysosomes in Schwann cells during
      Wallerian degeneration is Ca(2+)-dependent, and that it induces ATP release from
      Schwann cells.

PMID- 23142594
TI  - RANKL downregulates cell surface CXCR6 expression through JAK2/STAT3 signaling
      pathway during osteoclastogenesis.
AB  - The receptor activator of nuclear factor-kappaB ligand (RANKL), as a member of
      the tumor necrosis factor (TNF) family, plays an essential role in osteoclast
      differentiation and function. Chemokines and their receptors have recently been
      shown to play critical roles in osteoclastogenesis, however, whether CXCL16-CXCR6
      plays role in RANKL-mediated osteoclastogenesis is unknown. In this study, we
      first reported that RANKL decreased CXCR6 in a dose-dependent manner, which may
      be through deactivation of Akt and STAT3 signaling induced by CXCL16.
      Interestingly, RANKL-mediated CXCR6 reduction may be associated to the activation
      of STAT3 by phosphorylation. When STAT3 activation was blocked by JAK2/STAT3
      inhibitor AG490, RANKL failed to shut down CXCR6 expression during
      osteoclastogenesis. However, CXCL16 alone did not augment RANKL-mediated
      osteoclast differentiation and did not alter RANKL-receptor RANK mRNA expression.
      These results demonstrate that reduction of CXCL16-CXCR6 is critical in RANKL
      mediated osteoclastogenesis, which is mainly through the activation of JAK2/STAT3
      signaling. CXCL16-CXCR6 axis may become a novel target for the therapeutic
      intervention of bone resorbing diseases such as rheumatoid arthritis and
      osteoporosis.

PMID- 23142595
TI  - Different Ca2+-sensitivities between the EF-hands of T- and L-plastins.
AB  - Plastins are Ca(2+)-regulated actin-bundling proteins, and essential for
      developing and stabilizing actin cytoskeletons. T-plastin is expressed in
      epithelial and mesenchymal cells of solid tissues, whereas L-plastin is expressed
      in mobile cells such as hemopoietic cell lineages and cancer cells. Using various
      spectroscopic methods, gel-filtration chromatography, and isothermal titration
      calorimetry, we here demonstrate that the EF-hand motifs of both T- and L-plastin
      change their structures in response to Ca(2+), but the sensitivity to Ca(2+) is
      lower in T-plastin than in L-plastin. These results suggest that T-plastin is
      suitable for maintaining static cytoskeletons, whereas L-plastin is suitable for
      dynamic rearrangement of cytoskeletons.

PMID- 23142596
TI  - DNA-PK inhibition causes a low level of H2AX phosphorylation and homologous
      recombination repair in Medaka (Oryzias latipes) cells.
AB  - Nonhomologous end joining (NHEJ) and homologous recombination (HR) are known as
      DNA double-strand break (DSB) repair pathways. It has been reported that DNA-PK,
      a member of PI3 kinase family, promotes NHEJ and aberrant DNA-PK causes NHEJ
      deficiency. However, in this study, we demonstrate that a wild-type cell line
      treated with DNA-PK inhibitor and a mutant cell line with dysfunctional DNA-PK
      showed decreased HR efficiency in fish cells (Medaka, Oryzias latipes).
      Previously, we reported that the radiation-sensitive mutant RIC1 strain has a
      defect in the Histone H2AX phosphorylation after gamma-irradiation. Here, we
      showed that a DNA-PK inhibitor, NU7026, treatment resulted in significant
      reduction in the number of gammaH2AX foci after gamma-irradiation in wild-type
      cells, but had no significant effect in RIC1 cells. In addition, RIC1 cells
      showed significantly lower levels of DNA-PK kinase activity compared with wild
      type cells. We investigated NHEJ and HR efficiency after induction of DSBs. Wild
      type cells treated with NU7026 and RIC1 cells showed decreased HR efficiency.
      These results indicated that aberrant DNA-PK causes the reduction in the number
      of gammaH2AX foci and HR efficiency in RIC1 cells. We performed phosphorylated
      DNA-PKcs (Thr2609) and 53BP1 focus assay after gamma-irradiation. RIC1 cells
      showed significant reduction in the number of phosphorylated DNA-PKcs foci and no
      deference in the number of 53BP1 foci compared with wild-type cells. These
      results suggest that low level of DNA-PK activity causes aberrant DNA-PKcs
      autophosphorylation in RIC1 cells. It is known that 53BP1 is involved in both DNA
      PK dependent and independent NHEJ. Therefore we suggest that DNA-PK independent
      NHEJ repair DSBs under the condition of decreased DNA-PK activity, which causes
      reduction of HR efficiency.

PMID- 23142598
TI  - Phi (Phi) and psi (Psi) angles involved in malarial peptide bonds determine
      sterile protective immunity.
AB  - Modified HABP (mHABP) regions interacting with HLA-DRbeta1(*) molecules have a
      more restricted conformation and/or sequence than other mHABPs which do not fit
      perfectly into their peptide binding regions (PBR) and do not induce an
      acceptable immune response due to the critical role of their Phi and Psi torsion
      angles. These angle's critical role was determined in such highly immunogenic,
      protection-inducing response against experimental malaria using the conformers
      (mHABPs) obtained by (1)H-NMR and superimposed into HLA-DRbeta1(*)-like Aotus
      monkey molecules; their phi (Phi) and psi (Psi) angles were measured and the H
      bond formation between these molecules was evaluated. The aforementioned mHABP
      propensity to assume a regular conformation similar to a left-handed polyproline
      type II helix (PPII(L)) led to suggesting that favouring these conformations
      according to their amino acid sequence would lead to high antibody titre
      production and sterile protective immunity induction against malaria, thereby
      adding new principles or rules for vaccine development, malaria being one of
      them.

PMID- 23142597
TI  - The N-terminal ectodomain of Ninjurin1 liberated by MMP9 has chemotactic
      activity.
AB  - Ninjurin1 is known as an adhesion molecule promoting leukocyte trafficking under
      inflammatory conditions. However, the posttranslational modifications of
      Ninjurin1 are poorly understood. Herein, we defined the proteolytic cleavage of
      Ninjurin1 and its functions. HEK293T cells overexpressing the C- or N-terminus
      tagging mouse Ninjurin1 plasmid produced additional cleaved forms of Ninjurin1 in
      the lysates or conditioned media (CM). Two custom-made anti-Ninjurin1 antibodies,
      Ab(1-15) or Ab(139-152), specific to the N- or C-terminal regions of Ninjurin1
      revealed the presence of its shedding fragments in the mouse liver and kidney
      lysates. Furthermore, Matrix Metalloproteinase (MMP) 9 was responsible for
      Ninjurin1 cleavage between Leu(56) and Leu(57). Interestingly, the soluble N
      terminal Ninjurin1 fragment has structural similarity with well-known chemokines.
      Indeed, the CM from HEK293T cells overexpressing the GFP-mNinj1 plasmid was able
      to attract Raw264.7 cells in trans-well assay. Collectively, we suggest that the
      N-terminal ectodomain of mouse Ninjurin1, which may act as a chemoattractant, is
      cleaved by MMP9.

PMID- 23142599
TI  - Inhibition of vitellogenin gene induction by 2,3,7,8-tetrachlorodibenzo-p-dioxin
      is mediated by aryl hydrocarbon receptor 2 (AHR2) in zebrafish (Danio rerio).
AB  - Vitellogenins are hepatically derived yolk-protein precursors required for
      oogenesis in all oviparous teleosts. Altered gene-regulation of vitellogenesis by
      environmental contaminants can have profound effects on reproductive success, and
      ultimately population sustainability. To better understand chemical effects on
      vitellogenin gene regulation, we tested the hypothesis that activation of the
      aryl hydrocarbon receptor 2 (AHR2) by dioxin inhibits the estrogen receptor
      pathway regulation of 3 vitellogenin genes (vtg1-3) in vivo, using zebrafish
      (Danio rerio) as a model teleost. Using an embryo-larval bioassay, embryos were
      either treated with 1000 pptr (parts-per-trillion, pg/mL) 17alpha
      ethynylestradiol (EE2) alone from 6h post fertilization (hpf) to 4 days post
      fertilization (dpf), or pre-treated with dioxin (4-5 hpf) prior to EE2. Pre
      treatment with 400 pptr 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) or
      1,2,3,7,8-pentachlorodibenzo-p-dioxin inhibited the EE2 induction of vtg1, vtg2
      and vtg3 by >95% (p<=0.05). In comparison, a splice-blocking AHR2 morpholino used
      to down-regulate ahr2 expression significantly reduced the inhibition of vtg1,
      vtg2 and vtg3 by 400 pptr 2,3,7,8-TCDD (20.7-27.4% rescue). These studies
      demonstrate that 2,3,7,8-TCDD directly inhibits the vitellogenin pathway in vivo
      through activation of the AHR2. This work provides evidence for AHR2 dependent
      cross-talk inhibition of vitellogenin genes and offers insight into anti
      estrogenic reproductive effects observed in oviparous species exposed to AHR
      agonist contaminants.

PMID- 23142600
TI  - Toxicity of 15 veterinary pharmaceuticals in zebrafish (Danio rerio) embryos.
AB  - Extensive use of veterinary pharmaceuticals may result in contamination of water
      bodies adjacent to pasture land or areas where animal manure has been applied. In
      order to evaluate the potential risk to fish embryos 15 veterinary
      pharmaceuticals were investigated by use of an extended zebrafish embryo toxicity
      test. Chemical analysis of the exposure medium was performed by solid phase
      extraction-liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS) for 11
      of the compounds and potential metabolism by the embryos was studied for
      albendazole, febantel, fenbendazole and oxfendazole. Newly fertilized zebrafish
      eggs were exposed under static conditions in 96-well plates for 6 days to the
      pharmaceuticals: 5 antibacterials and 10 antiparasitics. Endpoints including
      mortality, malformations and other sublethal responses were recorded at 24, 48
      and 144 h post fertilization (hpf). The pharmaceuticals causing the highest
      toxicity were antiparasitics whereas the tested antibacterials, danofloxacin,
      enrofloxacin, tylosine, trimethoprim and oxytetracyclin had a much lower toxic
      potency in zebrafish embryos. Most toxic were fenbendazole, albendazole and
      flumethrin with no observed effect concentrations (NOECs) around 0.02 mg/L. The
      overall NOEC was determined by lethality for the following pharmaceuticals:
      albendazole, fenbendazole and oxfendazole. Sublethal endpoints, including
      malformations, side-laying embryos, tremors, reduced movements and altered heart
      rate increased the sensitivity of the tests and determined the overall NOECs for
      febantel, doramectin, ivermectin, flumethrin and toltrazuril. Exposure to
      doramectin and ivermectin caused a decrease in movements at 24 hpf and a decrease
      in heart rate at 48 hpf. Flumethrin exposure resulted in decreased time to
      hatching, except at the highest concentrations, and caused an increase in heart
      rate at 48 hpf. In contrast, toltrazuril caused an increased time to hatching and
      a decrease in heart rate. Chemical analysis of the exposure medium after the
      tests revealed great differences between nominal and measured concentrations,
      emphasizing the need of including analysis of the actual exposure concentrations.
      The results indicated that metabolism of albendazole into its sulfoxide protected
      the embryos from toxicity. Albendazole was metabolized efficiently into
      albendazole sulfoxide at lower exposure concentrations, resulting in reduced
      toxicity. At higher concentrations, an increasing proportion of albendazole
      remained unmetabolized and embryo mortality occurred. Metabolism by the embryos
      of febantel into fenbendazole and oxfendazole and of fenbendazole into
      oxfendazole was demonstrated. It is suggested that the toxic effect of febantel
      in zebrafish embryos is due to metabolism into fenbendazole.

PMID- 23142601
TI  - Mild enteropathy celiac disease: a wolf in sheep's clothing?

PMID- 23142602
TI  - Atypical presentation of miliary tuberculosis with hepatic involvement early
      after renal transplantation.

PMID- 23142603
TI  - Normal values of pharyngeal and esophageal 24-hour pH impedance in individuals on
      and off therapy and interobserver reproducibility.
AB  - BACKGROUND & AIMS: Combined pH and impedance monitoring can detect all types of
      reflux episodes within the esophageal lumen and the pharynx. We performed a
      multicenter study to establish normal values of pharyngeal and esophageal pH
      impedance monitoring in individuals on and off therapy and to determine the
      interobserver reproducibility of this technique. METHODS: We collected ambulatory
      24-hour pH-impedance recordings from 46 healthy subjects by using a bifurcated
      probe that allowed for detection of reflux events in the distal and proximal
      esophagus and pharynx. Data were collected when subjects had not received any
      medicine (off therapy) and after receiving 40 mg esomeprazole twice daily for 14
      days (on therapy). The interobserver agreement for the detection of reflux events
      was determined in 20 subjects off and on therapy. Results were expressed as
      median (interquartile range). RESULTS: Off therapy, subjects had a median of 32
      reflux events (17-45) in the distal esophagus and 3 (1-6) in the proximal
      esophagus; they had none in the pharynx. On therapy, subjects had a median number
      of 21 reflux events (6-37) in the distal esophagus and 2 (0-5) in the proximal
      esophagus; again, there were none in the pharynx. Interobserver agreement was
      good for esophageal reflux events but poor for pharyngeal events. CONCLUSIONS: We
      determined normal values of pharyngeal and gastroesophageal reflux events by 24
      hour pH-impedance monitoring of subjects receiving or not receiving esomeprazole
      therapy. Analyses of esophageal events were reproducible, but analyses of
      pharyngeal events were not; this limitation should be taken into account in
      further studies.

PMID- 23142604
TI  - Gastrointestinal complications of cystic fibrosis.
AB  - The cystic fibrosis transmembrane regulator protein (CFTR) is an ion channel in
      the apical surface of epithelial membranes that regulates other ion channels.
      Dysfunction of CFTR leads to the clinical entity of CF when mutations in CFTR are
      inherited in an autosomal recessive fashion. Although airway obstruction,
      inflammation, and infection are usually the most serious consequences of CFTR
      dysfunction because they lead to respiratory failure, CFTR dysfunction affects
      the intestinal tract and the pancreatic and hepatobiliary ducts in a similar
      fashion, leading to significant morbidity. This review outlines pathophysiology
      and common gastrointestinal ailments in the CF population along with current
      medical and surgical management.

PMID- 23142605
TI  - EGFR dependent subcellular communication was responsible for morphine mediated AC
      superactivation.
AB  - Compensatory adenylyl cyclase (AC) superactivation has been postulated to be
      responsible for the development of morphine tolerance and dependence, the
      underlying mechanism was demonstrated to comprise c-Src-dependent upregulation of
      AC5 within the lipid rafts. In the present study, we demonstrated that chronic
      morphine treatment sensitized EGFR signaling by augmenting EGFR phosphorylation
      and translocation into ER, which was essential for CRT-MOR tethering within the
      lipid rafts and AC5 superactivation. Intriguingly, synaptic clustering of CRT-MOR
      was dependent on EGFR phosphorylation and presumed to implicate in alignment and
      organization of synaptic compartments. Taken together, our data raised the
      possibility that an adaptive change in MOR and EGFR signal systems might
      establish CRT related subcellular communication, the signaling network within
      brain synaptic zone was proposed to implicate in morphine tolerance and
      dependence.

PMID- 23142607
TI  - Treatment with subcutaneous drainage in the pneumomediastinum and massive
      subcutaneous emphysema.

PMID- 23142606
TI  - Cannabinoid receptor 1 suppresses transient receptor potential vanilloid 1
      induced inflammatory responses to corneal injury.
AB  - Cannabinoid receptor type 1 (CB1)-induced suppression of transient receptor
      potential vanilloid type 1 (TRPV1) activation provides a therapeutic option to
      reduce inflammation and pain in different animal disease models through
      mechanisms involving dampening of TRPV1 activation and signaling events. As we
      found in both mouse corneal epithelium and human corneal epithelial cells (HCEC)
      that there is CB1 and TRPV1 expression colocalization based on overlap of
      coimmunostaining, we determined in mouse corneal wound healing models and in
      human corneal epithelial cells (HCEC) if they interact with one another to reduce
      TRPV1-induced inflammatory and scarring responses. Corneal epithelial debridement
      elicited in vivo a more rapid wound healing response in wildtype (WT) than in
      CB1(-/-) mice suggesting functional interaction between CB1 and TRPV1. CB1
      activation by injury is tenable based on the identification in mouse corneas of 2
      arachidonylglycerol (2-AG) with tandem LC-MS/MS, a selective endocannabinoid CB1
      ligand. Suppression of corneal TRPV1 activation by CB1 is indicated since
      following alkali burning, CB1 activation with WIN55,212-2 (WIN) reduced immune
      cell stromal infiltration and scarring. Western blot analysis of
      coimmunoprecipitates identified protein-protein interaction between CB1 and
      TRPV1. Other immunocomplexes were also identified containing transforming growth
      factor kinase 1 (TAK1), TRPV1 and CB1. CB1 siRNA gene silencing prevented
      suppression by WIN of TRPV1-induced TAK1-JNK1 signaling. WIN reduced TRPV1
      induced Ca(2+) transients in fura2-loaded HCEC whereas pertussis toxin (PTX)
      preincubation obviated suppression by WIN of such rises caused by capsaicin
      (CAP). Whole cell patch clamp analysis of HCEC showed that WIN blocked subsequent
      CAP-induced increases in nonselective outward currents. Taken together, CB1
      activation by injury-induced release of endocannabinoids such as 2-AG
      downregulates TRPV1 mediated inflammation and corneal opacification. Such
      suppression occurs through protein-protein interaction between TRPV1 and CB1
      leading to declines in TRPV1 phosphorylation status. CB1 activation of the GTP
      binding protein, G(i/o) contributes to CB1 mediated TRPV1 dephosphorylation
      leading to TRPV1 desensitization, declines in TRPV1-induced increases in currents
      and pro-inflammatory signaling events.

PMID- 23142608
TI  - Galanin, through GalR1 but not GalR2 receptors, decreases motivation at times of
      high appetitive behavior.
AB  - Galanin is a 29/30-amino acid long neuropeptide that has been implicated in many
      physiological and behavioral functions. Previous research has shown that i.c.v.
      administration of galanin strongly stimulates food intake in sated rats when food
      is freely available, but fails to stimulate this consumption when an operant
      response requirement is present. Using fixed ratio (FR) schedules, we sought to
      further clarify galanin's role in motivated behavior by administering galanin
      i.c.v. to rats working on fixed ratio schedules requiring either a low work
      condition (FR1) or higher work conditions (FR>1) to obtain a 0.2% saccharin
      reward. Rats in the FR>1 group were assigned to either an FR3, FR5 or FR7
      schedule of reinforcement. The rate of reinforcement decreased for only the FR>1
      group as compared to saline controls. Furthermore, injections of GalR1 receptor
      agonist M617 led to a similar, marginally significant decrease in the number of
      reinforcers received in the FR>1 condition, but a decrease was not seen after
      injections of GalR2 receptor agonist M1153. Taken together, these results show
      that galanin may be playing a role in decreasing motivation at times of high
      appetitive behavior, and that this effect is likely mediated by the GalR1
      receptor.

PMID- 23142609
TI  - Antidepressant-like effects of curcumin in WKY rat model of depression is
      associated with an increase in hippocampal BDNF.
AB  - Curcumin is the principal active ingredient found in turmeric (Curcuma longa), a
      plant used in traditional Asian diets and herbal medicines. It is known to have a
      wide range of biological actions including antidepressant-like effects which have
      been observed in stress-induced depression models. This study was designed to
      investigate the antidepressant potential of curcumin in a non-induced model of
      depression. Moreover, since brain derived neurotrophic factor (BDNF) has been
      implicated in antidepressant effects of many drugs, we also evaluated the effects
      of curcumin on BDNF in the hippocampus. Adult male Wistar Kyoto (WKY) rats, a
      putative model of depression, were injected acutely or chronically (10d) with 50,
      100, and 200mg/kg curcumin. Open field locomotor activity (OFLA) and forced swim
      test (FST), a measure of helplessness, were measured 1h after acute and 18-20h
      after last chronic injection. Results showed a dose-dependent reduction of
      immobility in the FST by curcumin in both acute and chronic studies, without any
      significant effect on OFLA. The effect of higher chronic curcumin dose in FST was
      still evident a week later. Chronic curcumin also resulted in a dose-dependent
      increase in hippocampal BDNF. This data provides evidence for an antidepressant
      like effect of curcumin, possibly through increased neurotrophic activity, in the
      WKY model of depression, and support the notion that curcumin may prove an
      effective and lasting natural antidepressant.

PMID- 23142610
TI  - Evaluation of emotional behaviors in young offspring of C57BL/6J mice after
      gestational and/or perinatal exposure to nicotine in six different time-windows.
AB  - Nicotine replacement treatments are being alternatively applied as an aid to
      smoking cessation during pregnancy. However, the effects of nicotine exposed at
      the prenatal stage on the emotional behaviors in offspring are not well
      understood due to the lack of systematic investigations. The current study has
      therefore initially aimed to evaluate emotional behaviors in young mouse
      offspring (postnatal day 28-36) which experienced gestational and/or perinatal
      nicotine exposure (GPNE) in six different time-windows. Pregnant C57BL/6J mice
      were exposed to nicotine via sweetened (2% sucrose) drinking water during 6
      different time-windows including gestational day 0-day 13 (G0-G13), G14-perinatal
      day 0 (P0), G0-P0, G14-P7, G0-P7, and P0-P7. During P28-P36 days, both male and
      female offspring were given a battery of behavioral tests including light and
      dark box test, marble burying behavior test, novelty-suppressed feeding test,
      sociability and social novelty preference test, social avoidance tube test, and
      elevated plus maze test. GPNE during G0-P0, G14-P0, G14-P7, and G0-P7 induced
      abnormal behaviors in male and female offspring to different extent. Results
      indicated that nicotine at any time points of gestational and/or perinatal period
      impairs emotional behaviors in offspring, and suggested certain time-windows for
      further neurochemical or molecular studies in relation with GPNE-induced
      emotional abnormalities.

PMID- 23142611
TI  - Changes in forelimb-hindlimb coordination after partial spinal lesions of
      different extent in the rat.
AB  - Forelimb-hindlimb coordination in adult rats moving freely along 2m long runway
      was investigated using the method of footprint recording. Rats were divided into
      3 groups with different extent of spinal lesions (T(9)). Before surgery rats
      moved with a mean locomotor speed of 73+/-20 to 96+/-18cms(-1), stride lengths of
      17.5+/-2.0 to 21.2+/-2.0cm, and trot like coordination. Early after surgery the
      locomotor speed and the stride lengths were decreased. The forelimb steps were
      shorter than hindlimb steps, which led to the occurrence of unpaired forelimb
      steps. Unpaired steps occurred when the hind paw print lay more than half the
      hindlimb stride length in front of the ipsilateral paw. The number of unpaired
      steps was negatively correlated with the difference between the fore- and
      hindlimb step lengths. The recovery of locomotor speed, stride length, and step
      sequence patterns took up to 3.5 months depending on the extent of lesion. In the
      last testings the coordination was characterized by increased distances between
      ipsilateral footprints leading to a change from an almost synchronized trot to a
      lesion-dependent walk. This change was accompanied by a switch from the use of
      both patterns A and C to the most frequent use of the Aa pattern that is better
      adapted to maintain the body balance. All locomotor changes depended on the
      extent of the injury of lateral and ventral funiculi. These results demonstrate
      that footprint analysis can be used for the evaluation of forelimb-hindlimb
      coordination after spinal lesion in rats.

PMID- 23142612
TI  - Synthesis of novel azo-resveratrol, azo-oxyresveratrol and their derivatives as
      potent tyrosinase inhibitors.
AB  - Ten azo compounds including azo-resveratrol (5) and azo-oxyresveratrol (9) were
      synthesized using a modified Curtius rearrangement and diazotization followed by
      coupling reactions with various phenolic analogs. All synthesized compounds were
      evaluated for their mushroom tyrosinase inhibitory activity. Compounds 4 and 5
      exhibited high tyrosinase inhibitory activity (56.25% and 72.75% at 50 MUM,
      respectively). The results of mushroom tyrosinase inhibition assays indicate that
      the 4-hydroxyphenyl moiety is essential for high inhibition and that 3,5
      dihydroxyphenyl and 3,5-dimethoxyphenyl derivatives are better for tyrosinase
      inhibition than 2,5-dimethoxyphenyl derivatives. Particularly, introduction of
      hydroxyl or methoxy group into the 4-hydroxyphenyl moiety diminished or
      significantly reduced mushroom tryosinase inhibition. Among the synthesized azo
      compounds, azo-resveratrol (5) showed the most potent mushroom tyrosinase
      inhibition with an IC(50) value of IC(50)=36.28 +/- 0.72 MUM, comparable to that
      of resveratrol, a well-known tyrosinase inhibitor.

PMID- 23142613
TI  - Redefining the structure-activity relationships of 2,6-methano-3-benzazocines.
      Part 8. High affinity ligands for opioid receptors in the picomolar Ki range:
      oxygenated N-(2-[1,1'-biphenyl]-4-ylethyl) analogues of 8-CAC.
AB  - N-[2-(4'-methoxy[1,1'-biphenyl]-4-yl)ethyl]-8-CAC (1) is a high affinity
      (K(i)=0.084 nM) ligand for the MU opioid receptor and served as the lead compound
      for this study. Analogues of 1 were made in hopes of identifying an SAR within a
      series of oxygenated (distal) phenyl derivatives. A number of new analogues were
      made having single-digit pM affinity for the MU receptor. The most potent was the
      3',4'-methylenedioxy analogue 18 (K(i)=1.6 pM).

PMID- 23142614
TI  - Synthesis and antiviral activity of novel HCV NS3 protease inhibitors with P4
      capping groups.
AB  - We have synthesized and evaluated a series of novel HCV NS3 protease inhibitors
      with various P4 capping groups, which include urea, carbamate, methoxy
      carboxamide, cyclic carbamate and amide, pyruvic amide, oxamate, oxalamide and
      cyanoguanidine. Most of these compounds are remarkably potent, exhibiting single
      digit to sub-nanomolar activity in the enzyme assay and cell-based replicon
      assay. Selected compounds were also evaluated in the protease-inhibitor-resistant
      mutant transient replicon assay, and they were found to show quite different
      potency profiles against a panel of HCV protease-inhibitor-resistant mutants.

PMID- 23142615
TI  - Discovery and SAR of a novel series of non-MPEP site mGlu5 PAMs based on an aryl
      glycine sulfonamide scaffold.
AB  - Herein we report the discovery and SAR of a novel series of non-MPEP site
      metabotropic glutamate receptor 5 (mGlu(5)) positive allosteric modulators (PAMs)
      based on an aryl glycine sulfonamide scaffold. This series represents a rare non
      MPEP site mGlu(5) PAM chemotype.

PMID- 23142616
TI  - Functional assay for shiga-like toxin via detection by antibody capture and
      multivalent galabiose binding.
AB  - A functional detection assay was developed for Escherichia coli secreted shiga
      like toxin based on antibody capture and visualization with a multivalent
      galabiose ligand. It was possible to detect verotoxin in medically relevant E.
      coli samples in a dose dependent fashion. This method is a new step towards
      measuring functional protein levels in complex mixtures, which can be used for
      diagnostic purposes in a clinical setting.

PMID- 23142617
TI  - Discovery and evolution of phenoxypiperidine hydroxyamide dual CCR3/H1
      antagonists. Part I.
AB  - The discovery of potent small molecule dual antagonists of the human CCR3 and
      H(1) receptors is described for the treatment of allergic diseases, for example,
      asthma and allergic rhinitis. Optimizing in vitro potency and metabolic
      stability, starting from a CCR1 lead compound, led to compound 20 with potent
      dual CCR3/H(1) activity and in vitro metabolic stability.

PMID- 23142618
TI  - Discovery of a novel series of 4-quinolone JNK inhibitors.
AB  - A novel series of highly selective JNK inhibitors based on the 4-quinolone
      scaffold was designed and synthesized. Structure based drug design was utilized
      to guide the compound design as well as improvements in the physicochemical
      properties of the series. Compound (13c) has an IC(50) of 62/170 nM for JNK1/2,
      excellent kinase selectivity and impressive efficacy in a rodent asthma model.

PMID- 23142619
TI  - The rise and fall of forensic hypnosis.
AB  - This paper examines the fortunes of the controversial use of hypnosis to
      'enhance' autobiographical memories in postwar America. From the 1950s through
      the early 1980s, hypnosis became increasingly popular as a means to exhume
      information thought to be buried within the mind. This practice was encouraged by
      lay understandings of memory drawn from a material culture full of new recording
      devices (motion pictures, tape and then video recorders); and during the years
      when the practice was becoming most popular and accepted, academic psychologists
      developed a contrary, reconstructive, account of memory that was put to use in a
      series of battles meant to put an end to hypnotic recall. But popular commitment
      to the idea of permanent memory 'recordings' sustained the practice and the
      assumptions about memory and self that were associated with it, and in the face
      of a culture of academic psychology fully committed to the idea of
      'reconstructive', malleable memory, a tidal wave of 'enhanced' memories swept
      America in the late 1980s and 1990s, in the so-called 'memory wars'. These, in
      turn, provoked academic psychologists to research the claims and counter claims
      central to the memory wars. The paper will also make an argument about the
      importance of lay knowledge in the psychological sciences explored in this paper:
      that popular psychological beliefs played a significant, even formative role in
      defining the nature of forensic psychological expertise, and also the framing of
      elite academic psychological research.

PMID- 23142620
TI  - Binding of single walled carbon nanotube to WT and mutant HIV-1 proteases:
      analysis of flap dynamics and binding mechanism.
AB  - Most of the currently treated HIV-1 protease (HIV-PR) inhibitors have been prone
      to suffer from the mutations associated drug resistance. Therefore, it is
      necessary to search for potent alternatives against the drug resistance. In the
      current study we have tested the single-walled carbon nanotube (SWCNT) as an
      inhibitor in wild type (WT) as well as in three primary mutants (I50V(PR),
      V82A(PR) and I84V(PR)) of the HIV-1-PR through docking the SWCNT in the active
      site region, and then performed all-atom MD simulations for the complexes. The
      conformational dynamics of HIV-PR with a 20 ns trajectory reveals that the SWCNT
      can effectively bind to the HIV-1-PR active site and regulate the flap dynamics
      such as maintaining the flap-flap closed. To gain an insight into the binding
      affinity, we also performed the MM-PBSA based binding free energy calculations
      for the four HIV-PR/SWCNT complexes. It was observed that, although the binding
      between the SWCNT and the HIV-PR decreases due to the mutations, the SWCNTs bind
      to the HIV-PRs 3-5 folds stronger than the most potent HIV-1-PR inhibitor,
      TMC114. Remarkably, the significant interactions with binding energy higher than
      1kcal/mol focus on the flap and active regions, which favors closing flap-flap
      and deactivating the active residues of the HIV-PR. The flap dynamics and binding
      strength information for HIV-PR and SWCNTs can help design SWCNT-based HIV-1-PR
      inhibitors.

PMID- 23142621
TI  - The Wolf method applied to the type I methane and carbon dioxide gas hydrates.
AB  - The Wolf method is introduced to handle long-range electrostatic interactions as
      a viable alternative to the most common methods, i.e., the Ewald Sum and its
      modifications (PPPM, PME and SPME), the Reaction Field method, and the Lekner
      technique for predicting the structure of type I clathrate hydrates. In
      comparison with the Ewald Sum family, it is computationally more time-saving and
      mathematically much simpler. It is also physically more meaningful than the Ewald
      Sum for disordered systems, liquids and crystals. In comparison with the Reaction
      Field method, it does not require the calculation of the dielectric constant
      during the simulation. The computational cost of the Wolf method is also much
      less than the Lekner method. NPT and NVT ensemble Monte Carlo simulations are
      performed to calculate energetic and structural properties of CH4 and CO2 gas
      hydrates at formation pressures and temperatures. The optimum values of the
      control parameters employed in the Wolf method are evaluated and the criteria
      used for the calculations are discussed. Finally, the results are compared with
      several simulation results and experimental data and satisfactory agreement is
      achieved.

PMID- 23142622
TI  - Hepatocyte senescence predicts progression in non-alcohol-related fatty liver
      disease.
AB  - BACKGROUND & AIMS: Models of non-alcohol-related fatty liver disease (NAFLD)
      reveal features of accelerated ageing, such as impaired regeneration, and an
      increased risk of hepatocellular carcinoma. The relation between accelerated
      ageing, disease progression and clinical outcome has not been previously
      investigated and is the subject of the current study. METHODS: Liver sections
      from 70 patients with NAFLD (105 biopsies) and 60 controls were studied for
      telomere length, nuclear area, DNA damage and cell cycle phase markers, using
      quantitative fluorescent in situ hybridization and immunohistochemistry. RESULTS:
      Hepatocyte telomeres were shorter in NAFLD than controls (p <0.0001). Hepatocytes
      in NAFLD demonstrated lack of cell cycle progression beyond G1/S phase and high
      level expression of p21, the universal cell cycle inhibitor (p=0.001). gamma
      H(2)AX expression increased with steatosis (p=0.01), indicating DNA damage, and
      was associated with shorter hepatocyte telomeres (p <0.0001). Hepatocyte p21
      expression correlated with fibrosis stage and diabetes mellitus, independently (p
      <0.001 and p=0.002, respectively). Further analysis revealed that an adverse
      liver-related outcome was strongly associated with higher hepatocyte p21
      expression and greater hepatocyte nuclear area (p=0.02 and p=0.006), but not with
      telomere length. In paired biopsies, changes in hepatocyte p21 expression and
      nuclear area mirrored changes in fibrosis stage (p=0.01 and p=0.006,
      respectively). CONCLUSIONS: These findings are consistent with hepatocyte
      senescence and permanent cell cycle arrest in NAFLD. Hepatocyte senescence
      correlated closely with fibrosis stage, diabetes mellitus, and clinical outcome.
      Hepatocyte p21 expression could be used as a prognostic marker and for
      stratification in clinical studies.

PMID- 23142623
TI  - Quorum sensing inhibitors: an overview.
AB  - Excessive and indiscriminate use of antibiotics to treat bacterial infections has
      lead to the emergence of multiple drug resistant strains. Most infectious
      diseases are caused by bacteria which proliferate within quorum sensing (QS)
      mediated biofilms. Efforts to disrupt biofilms have enabled the identification of
      bioactive molecules produced by prokaryotes and eukaryotes. These molecules act
      primarily by quenching the QS system. The phenomenon is also termed as quorum
      quenching (QQ). In addition, synthetic compounds have also been found to be
      effective in QQ. This review focuses primarily on natural and synthetic quorum
      sensing inhibitors (QSIs) with the potential for treating bacterial infections.
      It has been opined that the most versatile prokaryotes to produce QSI are likely
      to be those, which are generally regarded as safe. Among the eukaryotes, certain
      legumes and traditional medicinal plants are likely to act as QSIs. Such findings
      are likely to lead to efficient treatments with much lower doses of drugs
      especially antibiotics than required at present.

PMID- 23142624
TI  - Review: development of clinically relevant scaffolds for vascularised bone tissue
      engineering.
AB  - Clinical translation of scaffold-based bone tissue engineering (BTE) therapy
      still faces many challenges despite intense investigations and advancement over
      the years. To address these clinical barriers, it is important to analyse the
      current technical challenges in constructing a clinically relevant scaffold and
      subsequent clinical issues relating to bone repair. This review highlights the
      key challenges hampering widespread clinical translation of scaffold-based
      vascularised BTE, with a focus on the repair of large non-union defects. The main
      limitations of current scaffolds include the lack of sufficient vascularisation,
      insufficient mechanical strength as well as issues relating to the
      osseointegration of the bioresorbable scaffold and bone infection management.
      Critical insights on the current trends of scaffold technologies and future
      directions for advancing next-generation BTE scaffolds into the clinical realm
      are discussed. Considerations concerning regulatory approval and the route
      towards commercialisation of the scaffolds for widespread clinical utility will
      also be introduced. 

PMID- 23142625
TI  - Electroacupuncture reduces duration of postoperative ileus after laparoscopic
      surgery for colorectal cancer.
AB  - BACKGROUND & AIMS: We investigated the efficacy of electroacupuncture in reducing
      the duration of postoperative ileus and hospital stay after laparoscopic surgery
      for colorectal cancer. METHODS: We performed a prospective study of 165 patients
      undergoing elective laparoscopic surgery for colonic and upper rectal cancer,
      enrolled from October 2008 to October 2010. Patients were assigned randomly to
      groups that received electroacupuncture (n = 55) or sham acupuncture (n = 55),
      once daily from postoperative days 1-4, or no acupuncture (n = 55). The acupoints
      Zusanli, Sanyinjiao, Hegu, and Zhigou were used. The primary outcome was time to
      defecation. Secondary outcomes included postoperative analgesic requirement, time
      to ambulation, and length of hospital stay. RESULTS: Patients who received
      electroacupuncture had a shorter time to defecation than patients who received no
      acupuncture (85.9 +/- 36.1 vs 122.1 +/- 53.5 h; P < .001) and length of hospital
      stay (6.5 +/- 2.2 vs 8.5 +/- 4.8 days; P = .007). Patients who received
      electroacupuncture also had a shorter time to defecation than patients who
      received sham acupuncture (85.9 +/- 36.1 vs 107.5 +/- 46.2 h; P = .007).
      Electroacupuncture was more effective than no or sham acupuncture in reducing
      postoperative analgesic requirement and time to ambulation. In multiple linear
      regression analysis, an absence of complications and electroacupuncture were
      associated with a shorter duration of postoperative ileus and hospital stay after
      the surgery. CONCLUSIONS: In a clinical trial, electroacupuncture reduced the
      duration of postoperative ileus, time to ambulation, and postoperative analgesic
      requirement, compared with no or sham acupuncture, after laparoscopic surgery for
      colorectal cancer. ClinicalTrials.gov number, NCT00464425.

PMID- 23142627
TI  - Identification and characterization of salt-responsive microRNAs in Populus
      tomentosa by high-throughput sequencing.
AB  - Salt is one of the main environmental factors limiting plant growth and a better
      understanding of mechanisms of salt stress would aid efforts to bolster plant
      salt tolerance. MicroRNAs are well known for their important regulatory roles in
      response to abiotic stress in plants. In this study, high-throughput sequencing
      was employed to identify miRNAs in Populus tomentosa plantlets treated or not
      with salt (200 mM for 10 h). We found 141 conserved miRNAs belonging to 31
      families, 29 non-conserved but previously-known miRNAs belonging to 26 families,
      and 17 novel miRNAs. Under salt stress, 19 miRNAs belonging to seven conserved
      miRNA families were significantly downregulated, and two miRNAs belonging to two
      conserved miRNA families were upregulated. Of seven non-conserved miRNAs with
      significantly altered expression, five were downregulated and two were
      upregulated. Furthermore, eight miRNAs were validated by qRT-PCR and their
      dynamic differential expressions were analyzed. In addition, 269 target genes of
      identified miRNAs were predicted and categorized by function. These results
      provide new insights into salt-responsive miRNAs in Populus.

PMID- 23142628
TI  - Hot topics in men's health today.

PMID- 23142626
TI  - Central melanin-concentrating hormone influences liver and adipose metabolism via
      specific hypothalamic nuclei and efferent autonomic/JNK1 pathways.
AB  - BACKGROUND & AIMS: Specific neuronal circuits modulate autonomic outflow to liver
      and white adipose tissue. Melanin-concentrating hormone (MCH)-deficient mice are
      hypophagic, lean, and do not develop hepatosteatosis when fed a high-fat diet.
      Herein, we sought to investigate the role of MCH, an orexigenic neuropeptide
      specifically expressed in the lateral hypothalamic area, on hepatic and adipocyte
      metabolism. METHODS: Chronic central administration of MCH and adenoviral vectors
      increasing MCH signaling were performed in rats and mice. Vagal denervation was
      performed to assess its effect on liver metabolism. The peripheral effects on
      lipid metabolism were assessed by real-time polymerase chain reaction and Western
      blot. RESULTS: We showed that the activation of MCH receptors promotes
      nonalcoholic fatty liver disease through the parasympathetic nervous system,
      whereas it increases fat deposition in white adipose tissue via the suppression
      of sympathetic traffic. These metabolic actions are independent of parallel
      changes in food intake and energy expenditure. In the liver, MCH triggers lipid
      accumulation and lipid uptake, with c-Jun N-terminal kinase being an essential
      player, whereas in adipocytes MCH induces metabolic pathways that promote lipid
      storage and decreases lipid mobilization. Genetic activation of MCH receptors or
      infusion of MCH specifically in the lateral hypothalamic area modulated hepatic
      lipid metabolism, whereas the specific activation of this receptor in the arcuate
      nucleus affected adipocyte metabolism. CONCLUSIONS: Our findings show that
      central MCH directly controls hepatic and adipocyte metabolism through different
      pathways.

PMID- 23142629
TI  - Optimized enzymatic hydrolysis of DNA for LC-MS/MS analyses of adducts of 1
      methoxy-3-indolylmethyl glucosinolate and methyleugenol.
AB  - Mass spectrometric analyses of DNA adducts usually require enzymatic digestion of
      the DNA to nucleosides. The digestive enzymes used in our laboratory included a
      calf spleen phosphodiesterase, whose marketing was stopped recently. Using DNA
      adducted with bioactivated methyleugenol and 1-methoxy-3-indolylmethyl
      glucosinolate-each forming dA and dG adducts-we demonstrate that replacement of
      calf spleen phosphodiesterase (Merck) with bovine spleen phosphodiesterase (Sigma
      Aldrich) leads to unchanged results. Enzyme levels used for DNA digestion are
      extremely variable in different studies. Therefore, we sequentially varied the
      level of each of the three enzymes used. All dose (enzyme)-response (adduct
      level) curves involved a long plateau starting below the enzyme levels employed
      previously. Thus, we could reduce the amounts of micrococcal nuclease,
      phosphodiesterase, and alkaline phosphatase for quantitative DNA digestion by
      factors of 4, 2, and 333, respectively, compared to our previous protocols.
      Moreover, we observed significant phosphatase activity of both phosphodiesterase
      preparations used, which may affect the recovery of adducts with methods
      requiring digestion to 2'-deoxynucleoside-3'-monophosphates (e.g., (32)P
      postlabeling). In addition, the phosphodiesterase from Sigma-Aldrich, but not
      that from Merck, deaminated dA. This was irrelevant for the dA adducts studied,
      involving bonding at N(6), but might complicate the analysis of other dA adducts.

PMID- 23142630
TI  - Early impairment in a water-finding test in a longitudinal study of the Tg2576
      mouse model of Alzheimer's disease.
AB  - Behavioral assessments of mouse models of neurodegenerative disorders are useful
      for investigating the molecular basis of the pathologies of the diseases. Here,
      we investigated the utility of a water-finding test using a video tracking system
      as a tool for evaluating cognitive deficits in Alzheimer's disease model mice.
      Transgenic mice expressing mutant amyloid precursor protein that incorporated the
      Swedish mutation (Tg2576 mice) were tested for behavioral alterations at 3, 5, 6,
      or 10 months of age. Tg2576 mice, which are widely used as a model of Alzheimer's
      disease, exhibited significant cognitive deficits in the water-finding test as
      early as 5 months of age. The impairments progressively worsened at 6 and 10
      months of age. In addition, we analyzed spontaneous physical activities, such as
      locomotor activity, in the home-cage environment with an automated video analysis
      system (HomeCageScan). Our longitudinal study revealed that spontaneous behavior
      was altered in the Tg2576 mice, starting at the age of 10 months. Impairment in
      the Morris water maze (MWM) task was also first observed in the Tg2576 mice at
      the age of 10 months. These results indicated that the ability to perform the
      water-finding test was more susceptible to age-related cognitive deterioration in
      Tg2576 mice than the MWM test. We therefore propose that the water-finding test
      is a rapid and sensitive method that can be used to assess cognitive and/or
      behavioral deficits in mouse models of Alzheimer's disease.

PMID- 23142631
TI  - Automated correlation of single particle tilt pairs for Random Conical Tilt and
      Orthogonal Tilt Reconstructions.
AB  - One of the major methodological challenges in single particle electron microscopy
      is obtaining initial reconstructions which represent the structural heterogeneity
      of the dataset. Random Conical Tilt and Orthogonal Tilt Reconstruction techniques
      in combination with 3D alignment and classification can be used to obtain initial
      low-resolution reconstructions which represent the full range of structural
      heterogeneity of the dataset. In order to achieve statistical significance,
      however, a large number of 3D reconstructions, and, in turn, a large number of
      tilted image pairs are required. The extraction of single particle tilted image
      pairs from micrographs can be tedious and time-consuming, as it requires
      intensive user input even for semi-automated approaches. To overcome the
      bottleneck of manual selection of a large number of tilt pairs, we developed an
      algorithm for the correlation of single particle images from tilted image pairs
      in a fully automated and user-independent manner. The algorithm reliably
      correlates correct pairs even from noisy micrographs. We further demonstrate the
      applicability of the algorithm by using it to obtain initial references both from
      negative stain and unstained cryo datasets.

PMID- 23142632
TI  - Disease-associated mutations in the coil 2B domain of human lamin A/C affect
      structural properties that mediate dimerization and intermediate filament
      formation.
AB  - The lamin proteins are essential components of the nuclear lamina of eukaryotic
      cells, that are involved in a complex association mechanism to attain a
      functional supermolecular structure. Mutations of the lamin A/C gene are
      associated with several different neuromuscular diseases, and the detailed effect
      of disease-associated amino acid substitutions on the structure and stability of
      human lamin dimers is yet unknown. Here we present a structural and thermodynamic
      characterization by means of molecular dynamics simulations of the effect of
      pathological mutations (S326T, R331P, R331Q, E347K, E358K, M371K, and R377H) on
      the association of the coil 2B domains that mediate lamin A/C oligomerization.
      The structures attained during the simulations, along with the quantification of
      the contribution of each residue to the dimerization energies, support a lamin
      association mechanism mediated by homophilic intermolecular interactions promoted
      by dissociative conformational changes at distinct positions in the coiled coil.
      The pathogenic mutations can both increase or decrease the stability of lamin A/C
      dimers, and a possible correlation between the effect of the amino acid
      substitutions and disease onset and severity is presented.

PMID- 23142633
TI  - Ror2-Src signaling in metastasis of mouse melanoma cells is inhibited by NRAGE.
AB  - The receptor tyrosine kinase (RTK) Ror2 plays important roles in developmental
      morphogenesis and mediates the filopodia formation in Wnt5a-induced cell
      migration. However, the function of Ror2 in noncanonical Wnt signaling resulting
      in cancer metastasis is largely unknown. Here, we show that Ror2 expression is
      higher in the highly metastatic murine B16-BL6 melanoma cells than in the low
      metastatic variant B16 cells. Overexpression of Ror2 increases the metastasis
      ability of B16 cells, and knockdown of Ror2 reduces the migration ability of B16
      BL6 cells. Furthermore, the inhibition of Src kinase activity is critical for the
      Ror2-mediated cell migration upon Wnt5a treatment. The C-terminus of Ror2, which
      is deleted in brachydactyly type B (BDB), is essential for the mutual interaction
      with the SH1 domain of Src. Intriguingly, the Neurotrophin receptor-interacting
      MAGE homologue (NRAGE), which, as we previously reported, can remodel the
      cellular skeleton and inhibit cell-cell adhesion and metastasis of melanoma and
      pancreatic cancer, sharply blocks the interaction between Src and Ror2 and
      inhibits Ror2-mediated B16 cell migration by decreasing the activity of Src and
      focal adhesion kinase (FAK). Our data show that Ror2 is a potential factor in the
      tumorigenesis and metastasis in a Src-dependent manner that is negatively
      regulated by NRAGE.

PMID- 23142634
TI  - Therapeutic RNA aptamers in clinical trials.
AB  - RNA aptamers can fold into complex structures and bind with high affinity and
      selectivity to various macromolecules, viruses, and cells. They are isolated from
      a large pool of nucleic acids by a conceptually straightforward iterative
      selection process called SELEX. Aptamers have enormous potential as therapeutics
      due to their ability to bind to proteins and specifically inhibit their functions
      with minimal or no harmful side-effects. The first aptamer therapeutic was FDA
      approved in 2005 and a number of novel aptamer-based therapeutics are currently
      undergoing clinical trials for treating diseases such as macular degeneration,
      choroidal neovascularization, intravascular thrombus, acute coronary syndrome,
      von Willebrand factor related disorders, von Hippel-Lindau syndrome (VHL),
      angiomas, acute myeloid leukemia, renal cell carcinoma, non-small cell lung
      cancer, thrombotic thrombocytopenic purpura, and several others. In this review,
      we present aptamers in on-going, completed, and terminated clinical studies
      highlighting their mechanism of action as well as the inherent challenges of
      aptamer production and use.

PMID- 23142635
TI  - Developing and advancing dry powder inhalation towards enhanced therapeutics.
AB  - Enhanced therapeutics are drug products derived from existing generic drugs that
      provide additional benefits to the patients and the healthcare system. Enhanced
      therapeutics are considered to be an important and relatively low risk source of
      innovation. Pulmonary drug delivery is the major delivery route to treat chronic
      respiratory diseases and has been proven as a potential delivery route for
      complex drugs that cannot be delivered orally. Development of dry powder
      inhalation systems targets the delivery of fine drug particles to the deep lung
      surface by a combination of drug formulation, primary packaging and a device,
      whereby each contributes to the overall performance. Various methodologies for
      the non-clinical and clinical performance testing of orally inhaled products have
      been proposed and applied with variable success. Regulatory pathways have been
      developed and applied since. Considerable efforts have been made during the past
      decade to understand and optimize pulmonary drug delivery including their
      efficient commercial manufacturing. Pulmonary drug delivery remains an area of
      future innovation in the effective treatment of pulmonary diseases as well as the
      systemic delivery of systemically active complex drugs.

PMID- 23142636
TI  - Beneficial effects of cilostazol in a patient with recurrent ventricular
      fibrillation associated with early repolarization syndrome.

PMID- 23142638
TI  - Scapuloperoneal muscular dystrophy phenotype due to TRIM32-sarcotubular myopathy
      in South Dakota Hutterite.
AB  - Scapuloperoneal muscular dystrophy is a group of genetically heterogeneous
      disorders that share the phenotype of progressive weakness of scapular and
      anterior distal leg muscles. Recessive mutations in C-terminal domains of TRIM32
      result in limb-girdle muscular dystrophy 2H and sarcotubular myopathy, a rare
      congenital myopathy commonly seen in Hutterites. A scapuloperoneal phenotype has
      never been reported in sarcotubular myopathy. We here report a 23-year-old
      Hutterite man with a one-year history of progressive weakness predominantly
      involving the anterior tibial and left scapular muscles, and hyperCKemia. Biopsy
      of the anterior tibial muscle showed an active myopathy with non-rimmed vacuoles
      and mild denervation atrophy associated with reinnervation. The vacuoles are
      similar to those described in sarcotubular myopathy. TRIM32 sequencing revealed
      the common c.1459G>A mutation at homozygosity. A search for mutations in TRIM32
      should be considered in patients with scapuloperoneal muscular dystrophy, and
      especially in patients of Hutterite origin or with an atypical vacuolar myopathy.

PMID- 23142639
TI  - Going outside the neighborhood: the shopping patterns and adaptations of
      disadvantaged consumers living in the lower eastside neighborhoods of Detroit,
      Michigan.
AB  - This research employs household survey data and Geographic Information Systems
      (GIS) to explore the core assumption underlying much of the food desert discourse
      that socially and economically disadvantaged residents shop in their immediate
      neighborhood food environment. Findings indicate that disadvantaged consumers
      living on the lower eastside of Detroit, Michigan bypass their neighborhood food
      environments, which are disproportionately composed of convenience and party
      stores, to shop at independent, discount and regional supermarkets located in
      other parts of the city and in the suburbs. These trends hold despite various
      economic and physical constraints to their mobility. These findings complicate
      past assumptions that socially and economically disadvantaged residents living in
      a food desert shop within their neighborhood environment.

PMID- 23142640
TI  - Characterization of Ca(2+) signaling in the external yolk syncytial layer during
      the late blastula and early gastrula periods of zebrafish development.
AB  - Preferential loading of the complementary bioluminescent (f-aequorin) and
      fluorescent (Calcium Green-1 dextran) Ca(2+) reporters into the yolk syncytial
      layer (YSL) of zebrafish embryos, revealed the generation of stochastic patterns
      of fast, short-range, and slow, long-range Ca(2+) waves that propagate
      exclusively through the external YSL (E-YSL). Starting abruptly just after doming
      (~4.5h post-fertilization: hpf), and ending at the shield stage (~6.0hpf) these
      distinct classes of waves propagated at mean velocities of ~50 and ~4MUm/s,
      respectively. Although the number and pattern of these waves varied between
      embryos, their initiation site and arcs of propagation displayed a distinct
      dorsal bias, suggesting an association with the formation and maintenance of the
      nascent dorsal-ventral axis. Wave initiation coincided with a characteristic
      clustering of YSL nuclei (YSN), and their associated perinuclear ER, in the E
      YSL. Furthermore, the inter-YSN distance (IND) appeared to be critical such that
      Ca(2+) wave propagation occurred only when this was <~8MUm; an IND >~8MUm was
      coincidental with wave termination at shield stage. Treatment with the IP3R
      antagonist, 2-APB, the Ca(2+) buffer, 5,5'-dibromo BAPTA, and the SERCA-pump
      inhibitor, thapsigargin, resulted in a significant disruption of the E-YSL Ca(2+)
      waves, whereas exposure to the RyR antagonists, ryanodine and dantrolene, had no
      significant effect. These findings led us to propose that the E-YSL Ca(2+) waves
      are generated mainly via Ca(2+) release from IP3Rs located in the perinuclear ER,
      and that the clustering of the YSN is an essential step in providing a CICR
      pathway required for wave propagation. This article is part of a Special Issue
      entitled: 12th European Symposium on Calcium.

PMID- 23142641
TI  - Challenges measuring cardiomyocyte renewal.
AB  - Interventions to effect therapeutic cardiomyocyte renewal have received
      considerable interest of late. Such interventions, if successful, could give rise
      to myocardial regeneration in diseased hearts. Regenerative interventions fall
      into two broad categories, namely approaches based on promoting renewal of pre
      existing cardiomyocytes and approaches based on cardiomyogenic stem cell
      activity. The latter category can be further subdivided into approaches promoting
      differentiation of endogenous cardiomyogenic stem cells, approaches wherein
      cardiomyogenic stem cells are harvested, amplified or enriched ex vivo, and
      subsequently engrafted into the heart, and approaches wherein an exogenous stem
      cell is induced to differentiate in vitro, and the resulting cardiomyocytes are
      engrafted into the heart. There is disagreement in the literature regarding the
      degree to which cardiomyocyte renewal occurs in the normal and injured heart, the
      mechanism(s) by which this occurs, and the degree to which therapeutic
      interventions can enhance regenerative growth. This review discusses several
      caveats which are encountered when attempting to measure cardiomyocyte renewal in
      vivo which likely contribute, at least in part, to the disagreement regarding the
      levels at which this occurs in normal, injured and treated hearts. This article
      is part of a Special Issue entitled: Cardiomyocyte biology: Cardiac pathways of
      differentiation, metabolism and contraction.

PMID- 23142642
TI  - Identifying protein partners of CLN8, an ER-resident protein involved in neuronal
      ceroid lipofuscinosis.
AB  - Neuronal ceroid lipofuscinoses (NCLs) are a genetically heterogeneous group of
      neurodegenerative diseases characterized by cognitive and motor decline,
      epilepsy, visual loss and by lysosomal autofluorescent inclusions. Two distinct
      clinical phenotypes, the progressive epilepsy with mental retardation (EPMR) and
      a late-infantile variant of NCLs (CLN8-vLINCL) are associated with mutations in
      the CLN8 gene that encodes a transmembrane protein predominantly located to the
      endoplasmic reticulum (ER). To gain insight into the function of CLN8 protein, we
      employed the split-ubiquitin membrane-based yeast two-hybrid (MYTH) system, which
      detects protein-protein interactions in a membrane environment, using the full
      length human CLN8 as bait and a human brain cDNA library as prey. We identified
      several potential protein partners of CLN8 and especially referred to VAPA,
      c14orf1/hERG28, STX8, GATE16, BNIP3 and BNIP3L proteins that are associated with
      biologically relevant processes such as synthesis and transport of lipids,
      vesicular/membrane trafficking, autophagy/mitophagy and apoptosis. Interactions
      of CLN8 with VAPA and GATE16 were further validated by co-immunoprecipitation and
      co-localization assays in mammalian cells. Using a new C-terminal-oriented CLN8
      antibody, CLN8-VAPA interaction was also confirmed by co-staining in close
      spatial proximity within different CNS tissues. The results of this study shed
      light on potential interactome networks of CLN8 and provide a powerful starting
      point for understanding protein function(s) and molecular aspects of diseases
      associated with CLN8 deficiency.

PMID- 23142643
TI  - What comes around goes around: protein import and quality control in mitochondria
      and plastids.

PMID- 23142644
TI  - Micro-managing the circadian clock: The role of microRNAs in biological
      timekeeping.
AB  - Evolved under the selective pressures of a 24-h world, circadian timekeeping
      mechanisms are present in virtually all living organisms to coordinate daily
      rhythms in physiology and behavior. Until recently, the circadian clock was
      modeled as simple, interlocked transcription-translation feedback loops driving
      rhythms in gene expression of a handful of core clock genes. However, it has
      become evident that circadian clock regulation is immensely more complex than
      once thought and involves posttranscriptional, translational and
      posttranslational mechanisms. In particular, there has been a growing awareness
      of the vital role played by microRNAs (miRNAs) in regulating various aspects of
      circadian clock function. In this review, we will summarize our current knowledge
      of miRNA-dependent regulation of the circadian timing system in multiple
      organisms, including flies, mammals and higher plants. We will also discuss
      future perspectives for research on the role of miRNAs and noncoding RNAs in
      circadian regulation of health and disease.

PMID- 23142645
TI  - Hinge and chromoshadow of HP1alpha participate in recognition of K9 methylated
      histone H3 in nucleosomes.
AB  - The majority of the genome in eukaryotes is packaged into transcriptionally
      inactive chromatin. Heterochromatin protein 1 (HP1) is a major player in the
      establishment and maintenance of heterochromatin. HP1 specifically recognizes a
      methylated lysine residue at position 9 in histone H3 through its N-terminal
      chromo domain (CD). To elucidate the binding properties of HP1alpha to
      nucleosomes in vitro, we reconstituted nucleosomes containing histone H3
      trimethylated at lysine 9. HP1alpha exhibited high-affinity binding to
      nucleosomes containing methylated histone H3 in a nucleosome core-number
      dependent manner. The hinge region (HR) connecting the CD and C-terminal
      chromoshadow domain (CSD), and the CSD contributed to the selective binding of
      HP1alpha to histone H3 with trimethylated lysine 9 through weak DNA binding and
      by suppressing the DNA binding, respectively. We propose that not only the
      specific recognition of lysine 9 methylation of histone H3 by the CD but also the
      HR and the CSD cooperatively contribute to the selective binding of HP1alpha to
      histone H3 lysine 9 methylated nucleosomes.

PMID- 23142646
TI  - Detailed modeling of skin penetration--an overview.
AB  - In recent years, the combination of computational modeling and experiments has
      become a useful tool that is proving increasingly powerful for explaining
      biological complexity. As computational power is increasing, scientists are able
      to explore ever more complex models in finer detail and to explain very complex
      real world data. This work provides an overview of one-, two- and three
      dimensional diffusion models for penetration into mammalian skin. Besides
      diffusive transport this includes also binding of substances to skin proteins and
      metabolism. These models are based on partial differential equations that
      describe the spatial evolution of the transport process through the biological
      barrier skin. Furthermore, the work focuses on analytical and numerical
      techniques for this type of equations such as discretization schemes or
      homogenization (upscaling) techniques. Finally, the work compares different
      geometry models with respect to the permeability.

PMID- 23142648
TI  - Does Paricalcitol (Zemplar(r)) interfere with 1,25-dihydroxyvitamin D measurement
      by liquid chromatography-tandem mass spectrometry assays?

PMID- 23142649
TI  - Significant reduction of plasma gelsolin levels in patients with intracerebral
      hemorrhage.
AB  - BACKGROUND: Plasma gelsolin depletion has been associated with poor outcomes of
      critically ill patients. The present study was undertaken to investigate the
      plasma gelsolin concentrations in patients with intracerebral hemorrhage and to
      analyze the correlation of gelsolin with disease outcome. METHODS: Plasma
      gelsolin levels of 132 patients and 68 healthy controls were quantified by enzyme
      linked immunosorbent assay. Its correlation with 6-month mortality and
      unfavorable outcome (modified Rankin Scale score>2) was analyzed. RESULTS: Forty
      six patients (34.9%) died and 79 patients (59.9%) had an unfavorable outcome at 6
      months. Upon admission, plasma gelsolin level was significantly lower in patients
      than healthy controls. Plasma gelsolin level was highly correlated with National
      Institutes of Health Stroke Scale score. A forward stepwise logistic regression
      selected plasma gelsolin level as an independent predictor for 6-month mortality
      and unfavorable outcome of patients. A receiver operating characteristic curve
      analysis showed that plasma gelsolin level had high area under curve for
      predicting 6-month clinical outcomes. The prognostic value of gelsolin was
      similar to that of National Institutes of Health Stroke Scale score for 6-month
      clinical outcomes. Gelsolin improved the prognostic value of National Institutes
      of Health Stroke Scale score for 6-month unfavorable outcome, but not for 6-month
      mortality. CONCLUSION: Plasma gelsolin level represents a novel biomarker for
      predicting 6-month clinical outcomes in patients with intracerebral hemorrhage.

PMID- 23142647
TI  - New technologies in developing recombinant attenuated Salmonella vaccine vectors.
AB  - Recombinant attenuated Salmonella vaccine (RASV) vectors producing recombinant
      gene-encoded protective antigens should have special traits. These features
      ensure that the vaccines survive stresses encountered in the gastrointestinal
      tract following oral vaccination to colonize lymphoid tissues without causing
      disease symptoms and to result in induction of long-lasting protective immune
      responses. We recently described ways to achieve these goals by using regulated
      delayed in vivo attenuation and regulated delayed in vivo antigen synthesis,
      enabling RASVs to efficiently colonize effector lymphoid tissues and to serve as
      factories to synthesize protective antigens that induce higher protective immune
      responses. We also developed some additional new strategies to increase vaccine
      safety and efficiency. Modification of lipid A can reduce the inflammatory
      responses without compromising the vaccine efficiency. Outer membrane vesicles
      (OMVs) from Salmonella-containing heterologous protective antigens can be used to
      increase vaccine efficiency. A dual-plasmid system, possessing Asd+ and DadB+
      selection markers, each specifying a different protective antigen, can be used to
      develop multivalent live vaccines. These new technologies have been adopted to
      develop a novel, low-cost RASV synthesizing multiple protective pneumococcal
      protein antigens that could be safe for newborns/infants and induce protective
      immunity to diverse Streptococcus pneumoniae serotypes after oral immunization.

PMID- 23142650
TI  - Differentiation state-dependent effects of in vitro exposure to atrazine or its
      metabolite diaminochlorotriazine in a dopaminergic cell line.
AB  - AIMS: This study sought to determine the impact of in vitro exposure to the
      herbicide atrazine (ATR) or its major mammalian metabolite diaminochlorotriazine
      (DACT) on dopaminergic cell differentiation. MAIN METHODS: N27 dopaminergic cells
      were exposed for 24 or 48 h to ATR or DACT (12-300 MUM) and their effects on cell
      viability, ATP levels, ADP:ATP ratio and differentiation markers, such as soma
      size and neurite outgrowth, were assessed. KEY FINDINGS: Overall, intracellular
      ATP levels and soma size (decreased by ATR at >=12 MUM; 48 h) were the two
      parameters most sensitive to ATR exposure in undifferentiated and differentiating
      dopaminergic cells, respectively. At the morphological level, ATR, but not DACT,
      increased the percentage of morphologically abnormal undifferentiated N27 cells.
      On the other hand, exposure to DACT (300 MUM; 48 h), but not ATR, increased the
      ADP:ATP ratio regardless of the differentiation state and it moderately disrupted
      thin neurite outgrowth. Only the highest concentration of ATR or DACT (300 MUM)
      was cytotoxic after a longer exposure (48 h) and undifferentiated N27 cells were
      the least sensitive to the cytotoxic effects of ATR or DACT. SIGNIFICANCE: Our
      results suggest that the energy perturbation and morphological disruption of
      dopaminergic neuronal differentiation induced by ATR and, to a lesser extent,
      DACT, may be associated with reported neurological deficits caused by
      developmental ATR exposure in rodents.

PMID- 23142651
TI  - Cardiac dysfunction in diabetes.

PMID- 23142652
TI  - A direct morphometric comparison of five labeling protocols for multi-atlas
      driven automatic segmentation of the hippocampus in Alzheimer's disease.
AB  - Hippocampal volumetry derived from structural MRI is increasingly used to
      delineate regions of interest for functional measurements, assess efficacy in
      therapeutic trials of Alzheimer's disease (AD) and has been endorsed by the new
      AD diagnostic guidelines as a radiological marker of disease progression.
      Unfortunately, morphological heterogeneity in AD can prevent accurate demarcation
      of the hippocampus. Recent developments in automated volumetry commonly use multi
      template fusion driven by expert manual labels, enabling highly accurate and
      reproducible segmentation in disease and healthy subjects. However, there are
      several protocols to define the hippocampus anatomically in vivo, and the method
      used to generate atlases may impact automatic accuracy and sensitivity -
      particularly in pathologically heterogeneous samples. Here we report a fully
      automated segmentation technique that provides a robust platform to directly
      evaluate both technical and biomarker performance in AD among anatomically unique
      labeling protocols. For the first time we test head-to-head the performance of
      five common hippocampal labeling protocols for multi-atlas based segmentation,
      using both the Sunnybrook Longitudinal Dementia Study and the entire Alzheimer's
      Disease Neuroimaging Initiative 1 (ADNI-1) baseline and 24-month dataset. We
      based these atlas libraries on the protocols of (Haller et al., 1997; Killiany et
      al., 1993; Malykhin et al., 2007; Pantel et al., 2000; Pruessner et al., 2000),
      and a single operator performed all manual tracings to generate de facto "ground
      truth" labels. All methods distinguished between normal elders, mild cognitive
      impairment (MCI), and AD in the expected directions, and showed comparable
      correlations with measures of episodic memory performance. Only more inclusive
      protocols distinguished between stable MCI and MCI-to-AD converters, and had
      slightly better associations with episodic memory. Moreover, we demonstrate that
      protocols including more posterior anatomy and dorsal white matter compartments
      furnish the best voxel-overlap accuracies (Dice Similarity Coefficient=0.87
      0.89), compared to expert manual tracings, and achieve the smallest sample sizes
      required to power clinical trials in MCI and AD. The greatest distribution of
      errors was localized to the caudal hippocampus and the alveus-fimbria compartment
      when these regions were excluded. The definition of the medial body did not
      significantly alter accuracy among more comprehensive protocols. Voxel-overlap
      accuracies between automatic and manual labels were lower for the more
      pathologically heterogeneous Sunnybrook study in comparison to the ADNI-1 sample.
      Finally, accuracy among protocols appears to significantly differ the most in AD
      subjects compared to MCI and normal elders. Together, these results suggest that
      selection of a candidate protocol for fully automatic multi-template based
      segmentation in AD can influence both segmentation accuracy when compared to
      expert manual labels and performance as a biomarker in MCI and AD. 

PMID- 23142653
TI  - Automatic denoising of single-trial evoked potentials.
AB  - We present an automatic denoising method based on the wavelet transform to obtain
      single trial evoked potentials. The method is based on the inter- and intra-scale
      variability of the wavelet coefficients and their deviations from baseline
      values. The performance of the method is tested with simulated event related
      potentials (ERPs) and with real visual and auditory ERPs. For the simulated data
      the presented method gives a significant improvement in the observation of single
      trial ERPs as well as in the estimation of their amplitudes and latencies, in
      comparison with a standard denoising technique (Donoho's thresholding) and in
      comparison with the noisy single trials. For the real data, the proposed method
      largely filters the spontaneous EEG activity, thus helping the identification of
      single trial visual and auditory ERPs. The proposed method provides a simple,
      automatic and fast tool that allows the study of single trial responses and their
      correlations with behavior. 

PMID- 23142654
TI  - Capturing dynamic patterns of task-based functional connectivity with EEG.
AB  - A new approach to trace the dynamic patterns of task-based functional
      connectivity, by combining signal segmentation, dynamic time warping (DTW), and
      Quality Threshold (QT) clustering techniques, is presented.
      Electroencephalography (EEG) signals of 5 healthy subjects were recorded as they
      performed an auditory oddball and a visual modified oddball tasks. To capture the
      dynamic patterns of functional connectivity during the execution of each task,
      EEG signals are segmented into durations that correspond to the temporal windows
      of previously well-studied event-related potentials (ERPs). For each temporal
      window, DTW is employed to measure the functional similarities among channels.
      Unlike commonly used temporal similarity measures, such as cross correlation, DTW
      compares time series by taking into consideration that their alignment properties
      may vary in time. QT clustering analysis is then used to automatically identify
      the functionally connected regions in each temporal window. For each task, the
      proposed approach was able to establish a unique sequence of dynamic pattern
      (observed in all 5 subjects) for brain functional connectivity. 

PMID- 23142655
TI  - SOD2 deficiency in hematopoietic cells in mice results in reduced red blood cell
      deformability and increased heme degradation.
AB  - Among the three types of super oxide dismutases (SODs) known, SOD2 deficiency is
      lethal in neonatal mice owing to cardiomyopathy caused by severe oxidative
      damage. SOD2 is found in red blood cell (RBC) precursors, but not in mature RBCs.
      To investigate the potential damage to mature RBCs resulting from SOD2 deficiency
      in precursor cells, we studied RBCs from mice in which fetal liver stem cells
      deficient in SOD2 were capable of efficiently rescuing lethally irradiated host
      animals. These transplanted animals lack SOD2 only in hematopoietically generated
      cells and live longer than SOD2 knockouts. In these mice, approximately 2.8% of
      their total RBCs in circulation are iron-laden reticulocytes, with numerous
      siderocytic granules and increased protein oxidation similar to that seen in
      sideroblastic anemia. We have studied the RBC deformability and oxidative stress
      in these animals and the control group by measuring them with a microfluidic
      ektacytometer and assaying fluorescent heme degradation products with a
      fluorimeter, respectively. In addition, the rate of hemoglobin oxidation in RBCs
      from these mice and the control group were measured spectrophotometrically. The
      results show that RBCs from these SOD2-deficient mice have reduced deformability,
      increased heme degradation products, and an increased rate of hemoglobin
      oxidation compared with control animals, indicative of increased RBC oxidative
      stress.

PMID- 23142656
TI  - Hits identified in library screening demonstrate selective CYP17A1 lyase
      inhibition.
AB  - A screening of structurally different steroid hormone synthesis inhibitors was
      performed in order to find a starting point for the development of a new
      inhibitor of the bifunctional steroidogenic enzyme CYP17A1. Emphasis was placed
      on determination of selectivity between the two catalytic steps, namely 17alpha
      hydroxylase and C(17,20)-lyase. For that purpose a new inhibition assay has been
      developed. Hits identified within this novel assay demonstrated selective
      inhibition of CYP17A1 lyase activity, and thus mark the basis for the development
      of selective C(17,20)-lyase inhibitors for the treatment of prostate cancer.

PMID- 23142657
TI  - Subtype-specific response to bevacizumab is reflected in the metabolome and
      transcriptome of breast cancer xenografts.
AB  - Antiangiogenic therapy with bevacizumab has shown varying results in breast
      cancer clinical trials. Identifying robust biomarkers for selecting patients who
      may benefit from such treatment and for monitoring response is important for the
      future use of bevacizumab. Two established xenograft models representing basal
      like and luminal-like breast cancer were used to study bevacizumab treatment
      response on the metabolic and gene expression levels. Tumor samples were obtained
      from mice treated with bevacizumab, doxorubicin or a combination of the two
      drugs, and high resolution magic angle spinning magnetic resonance spectroscopy
      and gene expression microarray analysis was performed. Combination treatment with
      bevacizumab showed the strongest growth inhibiting effect in basal-like tumors,
      and this was reflected by a significant change in the metabolomic and
      transcriptomic profiles. In the luminal-like xenografts, addition of bevacizumab
      did not improve the effect of doxorubicin. On the global transcriptomic level,
      the largest gene expression changes were observed for the most efficient
      treatment in both models. Glycerophosphocholine showed opposite response in the
      treated xenografts compared with untreated controls; lower in basal-like and
      higher in luminal-like tumors. Comparing combination therapy with doxorubicin
      monotherapy in basal-like xenografts, 14 genes showed significant differential
      expression, including very low density lipoprotein receptor (VLDLR) and
      hemoglobin, theta 1 (HBQ1). Bevacizumab-treated tumors were associated with a
      more hypoxic phenotype, while no evidence was found for associations between
      bevacizumab treatment and vascular invasion or tumor grade. This study underlines
      the importance of characterizing biological differences between subtypes of
      breast cancer to identify personalized biomarkers for improved patient
      stratification and evaluation of response to therapy.

PMID- 23142658
TI  - Metabolomics approach for predicting response to neoadjuvant chemotherapy for
      breast cancer.
AB  - Breast cancer is a clinically heterogeneous disease, which necessitates a variety
      of treatments and leads to different outcomes. As an example, only some women
      will benefit from chemotherapy. Identifying patients who will respond to
      chemotherapy and thereby improve their long-term survival has important
      implications to treatment protocols and outcomes, while identifying non
      responders may enable these patients to avail themselves of other investigational
      approaches or other potentially effective treatments. In this study, serum
      metabolite profiling was performed to identify potential biomarker candidates
      that can predict response to neoadjuvant chemotherapy for breast cancer.
      Metabolic profiles of serum from patients with complete (n = 8), partial (n = 14)
      and no response (n = 6) to chemotherapy were studied using a combination of
      nuclear magnetic resonance (NMR) spectroscopy, liquid chromatography-mass
      spectrometry (LC-MS) and statistical analysis methods. The concentrations of four
      metabolites, three (threonine, isoleucine, glutamine) from NMR and one (linolenic
      acid) from LC-MS were significantly different when comparing response to
      chemotherapy. A prediction model developed by combining NMR and MS derived
      metabolites correctly identified 80% of the patients whose tumors did not show
      complete response to chemotherapy. These results show promise for larger studies
      that could result in more personalized treatment protocols for breast cancer
      patients.

PMID- 23142659
TI  - Estimated copy number of Bacillus anthracis plasmids pXO1 and pXO2 using digital
      PCR.
AB  - We evaluated digital PCR (dPCR) to directly enumerate plasmid and chromosome
      copies in three strains of Bacillus anthracis. Copy number estimates based on
      conventional quantitative PCR (qPCR) highlighted the variability of using qPCR to
      measure copy number whereas estimates based on direct sequencing are comparable
      to dPCR.

PMID- 23142660
TI  - Molecular identification of t(w5): Vps52 promotes pluripotential cell
      differentiation through cell-cell interactions.
AB  - After implantation, pluripotent epiblasts are converted to embryonic ectoderm
      through cell-cell interactions that significantly change the transcriptional and
      epigenetic networks. An entree to understanding this vital developmental
      transition is the t(w5) mutation of the mouse t complex. This mutation produces
      highly specific defects in the embryonic ectoderm before gastrulation, leading to
      death of the embryonic ectoderm. Using a positional cloning approach, we have now
      identified the mutated gene, completing a decades-long search. The gene, vacuolar
      protein sorting 52 (Vps52), is a mouse homolog of yeast VPS52 that is involved in
      the retrograde trafficking of endosomes. Our data suggest that Vps52 acts in
      extraembryonic tissues to support the growth and differentiation of embryonic
      ectoderm via cell-cell interactions. It is also required in the formation of
      embryonic structures at a later stage of development, revealing hitherto unknown
      functions of Vps52 in the development of a multicellular organism.

PMID- 23142661
TI  - Maturation-promoting activity of SATB1 in MGE-derived cortical interneurons.
AB  - The generation of cortical interneuron subtypes is controlled by genetic programs
      that are activated in the ventral forebrain and unfold during the prolonged
      period of inhibitory neuron development. The LIM-homeodomain protein LHX6 is
      critical for the development of all cortical interneurons originating in the
      medial ganglionic eminence, but the molecular mechanisms that operate downstream
      of LHX6 to control the terminal differentiation of somatostatin- and parvalbumin
      expressing interneurons within the cortex remain unknown. Here, we provide
      evidence that the nuclear matrix and genome organizer protein SATB1 is induced by
      neuronal activity and functions downstream of Lhx6 to control the transition of
      tangentially migrating immature interneurons into the terminally differentiated
      Somatostatin (SST)-expressing subtype. Our experiments provide a molecular
      framework for understanding the genetic and epigenetic mechanisms by which
      specified but immature cortical interneurons acquire the subtype-defining
      molecular and morphophysiological characteristics that allow them to integrate
      and function within cortical circuits.

PMID- 23142662
TI  - MDA5 detects the double-stranded RNA replicative form in picornavirus-infected
      cells.
AB  - RIG-I and MDA5 are cytosolic RNA sensors that play a critical role in innate
      antiviral responses. Major advances have been made in identifying RIG-I ligands,
      but our knowledge of the ligands for MDA5 remains restricted to data from
      transfection experiments mostly using poly(I:C), a synthetic dsRNA mimic. Here,
      we dissected the IFN-alpha/beta-stimulatory activity of different viral RNA
      species produced during picornavirus infection, both by RNA transfection and in
      infected cells in which specific steps of viral RNA replication were inhibited.
      Our results show that the incoming genomic plus-strand RNA does not activate
      MDA5, but minus-strand RNA synthesis and production of the 7.5 kbp replicative
      form trigger a strong IFN-alpha/beta response. IFN-alpha/beta production does not
      rely on plus-strand RNA synthesis and thus generation of the partially double
      stranded replicative intermediate. This study reports MDA5 activation by a
      natural RNA ligand under physiological conditions.

PMID- 23142663
TI  - DNA binding by GATA transcription factor suggests mechanisms of DNA looping and
      long-range gene regulation.
AB  - GATA transcription factors regulate transcription during development and
      differentiation by recognizing distinct GATA sites with a tandem of two conserved
      zinc fingers, and by mediating long-range DNA looping. However, the molecular
      basis of these processes is not well understood. Here, we determined three
      crystal structures of the full DNA-binding domain (DBD) of human GATA3 protein,
      which contains both zinc fingers, in complex with different DNA sites. In one
      structure, both zinc fingers wrap around a palindromic GATA site, cooperatively
      enhancing the binding affinity and kinetic stability. Strikingly, in the other
      two structures, the two fingers of GATA DBD bind GATA sites on different DNA
      molecules, thereby bridging two separate DNA fragments. This was confirmed in
      solution by an in-gel fluorescence resonance energy transfer analysis. These
      findings not only provide insights into the structure and function of GATA
      proteins but also shed light on the molecular basis of long-range gene
      regulation.

PMID- 23142664
TI  - Human CST has independent functions during telomere duplex replication and C
      strand fill-in.
AB  - Human CST (CTC1-STN1-TEN1) is an RPA-like complex that is needed for efficient
      replication through the telomere duplex and genome-wide replication restart after
      fork stalling. Here, we show that STN1/CST has a second function in telomere
      replication during G-overhang maturation. Analysis of overhang structure after
      STN1 depletion revealed normal kinetics for telomerase-mediated extension in S
      phase but a delay in subsequent overhang shortening. This delay resulted from a
      defect in C-strand fill-in. Short telomeres exhibited the fill-in defect but
      normal telomere duplex replication, indicating that STN1/CST functions
      independently in these processes. Our work also indicates that the requirement
      for STN1/CST in telomere duplex replication correlates with increasing telomere
      length and replication stress. Our results provide direct evidence that STN1/CST
      participates in C-strand fill-in. They also demonstrate that STN1/CST
      participates in two mechanistically separate steps during telomere replication
      and identify CST as a replication factor that solves diverse replication
      associated problems.

PMID- 23142665
TI  - Structures of the Sgt2/SGTA dimerization domain with the Get5/UBL4A UBL domain
      reveal an interaction that forms a conserved dynamic interface.
AB  - In the cytoplasm, the correct delivery of membrane proteins is an essential and
      highly regulated process. The posttranslational targeting of the important tail
      anchor membrane (TA) proteins has recently been under intense investigation. A
      specialized pathway, called the guided entry of TA proteins (GET) pathway in
      yeast and the transmembrane domain recognition complex (TRC) pathway in
      vertebrates, recognizes endoplasmic-reticulum-targeted TA proteins and delivers
      them through a complex series of handoffs. An early step is the formation of a
      complex between Sgt2/SGTA, a cochaperone with a presumed ubiquitin-like-binding
      domain (UBD), and Get5/UBL4A, a ubiquitin-like domain (UBL)-containing protein.
      We structurally characterize this UBD/UBL interaction for both yeast and human
      proteins. This characterization is supported by biophysical studies that
      demonstrate that complex formation is mediated by electrostatics, generating an
      interface that has high-affinity with rapid kinetics. In total, this work
      provides a refined model of the interplay of Sgt2 homologs in TA targeting.

PMID- 23142666
TI  - Charting monosynaptic connectivity maps by two-color light-sheet fluorescence
      microscopy.
AB  - Cellular resolution three-dimensional (3D) visualization of defined,
      fluorescently labeled long-range neuronal networks in the uncut adult mouse brain
      has been elusive. Here, a virus-based strategy is described that allowed
      fluorescent labeling of centrifugally projecting neuronal populations in the
      ventral forebrain and their directly, monosynaptically connected bulbar
      interneurons upon a single stereotaxic injection into select neuronal
      populations. Implementation of improved tissue clearing combined with light-sheet
      fluorescence microscopy permitted imaging of the resulting connectivity maps in a
      single whole-brain scan. Subsequent 3D reconstructions revealed the exact
      distribution of the diverse neuronal ensembles monosynaptically connected with
      distinct bulbar interneuron populations. Moreover, rehydratation of brains after
      light-sheet fluorescence imaging enabled the immunohistochemical identification
      of synaptically connected neurons. Thus, this study describes a method for
      identifying monosynaptic connectivity maps from distinct, virally labeled
      neuronal populations that helps in better understanding of information flow in
      neural systems.

PMID- 23142667
TI  - Role of DNA polymerases in repeat-mediated genome instability.
AB  - Expansions of simple DNA repeats cause numerous hereditary diseases in humans. We
      analyzed the role of DNA polymerases in the instability of Friedreich's ataxia
      (GAA)(n) repeats in a yeast experimental system. The elementary step of expansion
      corresponded to ~160 bp in the wild-type strain, matching the size of Okazaki
      fragments in yeast. This step increased when DNA polymerase alpha was mutated,
      suggesting a link between the scale of expansions and Okazaki fragment size.
      Expandable repeats strongly elevated the rate of mutations at substantial
      distances around them, a phenomenon we call repeat-induced mutagenesis (RIM).
      Notably, defects in the replicative DNA polymerases delta and epsilon strongly
      increased rates for both repeat expansions and RIM. The increases in repeat
      mediated instability observed in DNA polymerase delta mutants depended on
      translesion DNA polymerases. We conclude that repeat expansions and RIM are two
      sides of the same replicative mechanism.

PMID- 23142668
TI  - Effects of gene length on the dynamics of gene expression.
AB  - In Escherichia coli, the nucleotide length of a gene is bound to affect its
      expression dynamics. From simulations of a stochastic model of gene expression at
      the nucleotide and codon levels we show that, within realistic parameter values,
      the nucleotide length affects RNA and protein mean levels, as well as the
      expected transient time for RNA and protein numbers to change, following a
      signal. Fluctuations in RNA and protein numbers are found to be minimized for a
      small range of lengths, which matches the means of the distributions of lengths
      found in E. coli of both essential and non-essential genes. The variance of the
      length distribution for essential genes is found to be smaller than for non
      essential genes, implying that these distributions are far from random. Finally,
      gene lengths are shown to affect the kinetics of a genetic switch, namely, the
      correlation between temporal proteins numbers, the stability of the two noisy
      attractors of the switch, and how biased is the choice of noisy attractor. The
      stability increases with gene length due to increased 'memory' about the previous
      states of the switch. We argue that, by affecting the dynamics of gene expression
      and of genetic circuits, gene lengths are subject to selection.

PMID- 23142670
TI  - The production effect benefits performance in between-subject designs: a meta
      analysis.
AB  - Producing (e.g., saying, mouthing) some items and silently reading others has
      been shown to result in a reliable advantage favoring retention of the produced
      compared to non-produced items at test. However, evidence has been mixed as to
      whether the benefits of production are limited to within- as opposed to between
      subject designs. It has even been suggested that the within-subjects nature of
      the production effect may be one of its defining characteristics. Meta-analytic
      techniques were applied to evaluate this claim. Findings indicated a moderate
      effect of production on recognition memory when varied between-subjects (g=0.37).
      This outcome suggests that the production effect is not defined as an exclusively
      within-subject occurrence.

PMID- 23142669
TI  - LIBER8 design and methods: an integrative intervention for loss of control eating
      among African American and White adolescent girls.
AB  - Loss of control (LOC) eating affects a significant number of adolescents of all
      racial and ethnic backgrounds and is associated with numerous psychosocial
      problems, including depression, anxiety, low self-esteem, body dissatisfaction,
      and weight concerns. However, empirically validated, culturally sensitive
      treatments for adolescents with these disordered eating behaviors are not
      available. This pilot project involved designing a developmentally and culturally
      appropriate treatment for LOC eating for adolescent girls. We intend to conduct
      multiple focus groups with adolescent girls who engage in LOC eating, and their
      primary caregivers. Data from these groups will inform the subsequent creation of
      a manualized treatment protocol. We will then evaluate the efficacy of this
      intervention (LIBER8-Linking Individuals Being Emotionally Real) to reduce LOC
      eating. This intervention will integrate components of dialectical behavior
      therapy, such as mindfulness and distress tolerance skills training, and
      cognitive-behavioral therapy. We will also integrate text-messaging, a key
      adolescent communication strategy, as a means of self-monitoring. Participants
      meeting study criteria will be offered participation in this 12-week randomized
      controlled trial comparing LIBER8 to a weight management control condition
      (2BFit). We hypothesize that this intervention will serve to reduce LOC eating,
      as well as improve psychosocial functioning as evidenced by decreased depression,
      anxiety, eating disorder cognitions, emotional eating, impulsivity, and improved
      quality of life. The feasibility and acceptability of this intervention will be
      extensively evaluated with the explicit intent of informing a subsequent larger
      randomized controlled trial.

PMID- 23142671
TI  - Synthesis and biological evaluation of some hydrazone derivatives as new
      anticandidal and anticancer agents.
AB  - New hydrazone derivatives were synthesized via the nucleophilic addition
      elimination reaction of 2-[(1-methyl-1H-tetrazol-5-yl)thio)]acetohydrazide with
      aromatic aldehydes/ketones. The compounds were tested in vitro against various
      Candida species and compared with ketoconazole. Genotoxicity of the most
      effective anticandidal compounds was evaluated by umuC and Ames assays. All
      compounds were also investigated for their cytotoxic effects on NIH3T3 and A549
      cell lines. Compound 8 was the most effective antifungal derivative against C.
      albicans (ATCC-90028) with a MIC value of 0.05 mg/mL. Compound 5 can be
      identified as the most promising anticancer agent against A549 cancer cell lines
      due to its inhibitory effect on A549 cell lines and low toxicity to NIH3T3 cells.

PMID- 23142672
TI  - Synthesis, structures and urease inhibition studies of Schiff base metal
      complexes derived from 3,5-dibromosalicylaldehyde.
AB  - Eleven mononuclear copper(II), nickel(II), zinc(II) and cobalt(II) complexes of
      Schiff base ligands derived from 3,5-dibromosalicylaldehyde/3,5
      dichlorosalicylaldehyde were synthesized and determined by single crystal X-ray
      analysis. The crystal structures of complexes 1, 2, 4, 5, 6, 8 and 11 present the
      square-planar coordination geometry at the metal center and complexes 7, 9 and 10
      show the distorted tetrahedral geometry. While one copper center in 3 has a
      square-planar geometry, the other copper is slightly distorted square-planar. The
      inhibitory activities of all the obtained complexes were tested in vitro against
      jack bean urease. It was found that Schiff base copper(II) complexes 1, 3, 5, 8
      and 11 showed strong urease inhibitory activities (IC(50) = 1.51-3.52 MUM)
      compared with acetohydroxamic acid (IC(50) = 62.52 MUM), which was a positive
      reference. Their structure-activity relationships were further discussed.

PMID- 23142673
TI  - Mechanistic aspects of the photodynamic inactivation of Candida albicans induced
      by cationic porphyrin derivatives.
AB  - Photodynamic inactivation of Candida albicans produced by 5-(4-trifluorophenyl)
      10,15,20-tris(4-N,N,N-trimethylammoniumphenyl)porphyrin (TFAP(3+)), 5,10,15,20
      tetrakis(4-N,N,N-trimethylammoniumphenyl)porphyrin (TMAP(4+)) and 5,10,15,20
      tetrakis(4-N-methylpyridyl)porphyrin (TMPyP(4+)) was investigated to obtain
      insight about the mechanism of cellular damage. In solution, absorption
      spectroscopic studies showed that these cationic porphyrins interact strongly
      with calf thymus DNA. The electrophoretic analysis indicated that photocleavage
      of DNA induced by TFAP(3+) took place after long irradiation periods (>5 h). In
      contrast, TMAP(4+) produced a marked reduction in DNA band after 1 h irradiation.
      In C. albicans, these cationic porphyrins produced a ~3.5 log decrease in
      survival when the cell suspensions (10(7) cells/mL) were incubated with 5 MUM
      photosensitizer and irradiated for 30 min with visible light (fluence 162
      J/cm(2)). After this treatment, modifications of genomic DNA isolated from C.
      albicans cells were not found by electrophoresis. Furthermore, transmission
      electron microscopy showed structural changes with appearance of low density
      areas into the cells and irregularities in cell barriers. However, the
      photodamage to the cell envelope was insufficient to cause the release of
      intracellular biopolymers. Therefore, modifications in the cytoplasmic
      biomolecules and alteration in the cell barriers could be mainly involved in C.
      albicans photoinactivation.

PMID- 23142674
TI  - Synthesis, anticancer activities and molecular modeling studies of novel indole
      retinoid derivatives.
AB  - In this study, novel (E)-3-(5-substituted-1H-indol-3-yl)-1-(5,5,8,8-tetramethyl
      5,6,7,8-tetrahydronaphthalen-2-yl)prop-2-en-1-one (5(a-e)) derivatives were
      synthesized and their anticancer effects were determined in vitro. Novel indole
      retinoid compounds except 5e have anti-proliferative capacity in liver, breast
      and colon cancer cell lines. This anti-proliferative effect was further analyzed
      in breast cancer cell line panel by using the most potent compound 5a. It was
      determined that 5a can inhibit proliferation at very low IC(50) concentrations in
      all of the breast cancer cell lines. Here, we present some evidence on apoptotic
      termination of cancer cell proliferation which may be primarily driven by the
      inhibition of RXRalpha and, to a lesser extent, RXRgamma.

PMID- 23142675
TI  - Synthesis of N-(5-chloro-6-(quinolin-3-yloxy)pyridin-3-yl)benzenesulfonamide
      derivatives as non-TZD peroxisome proliferator-activated receptor gamma
      (PPARgamma) agonist.
AB  - The thiazolidinediones (TZDs) are a class of oral antidiabetic drugs that improve
      insulin sensitivity in patients with type 2 diabetes. Although the mechanism by
      which the TZDs lower insulin resistance is unclear, they are known to target the
      peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear hormone
      receptor. Ligands for PPARgamma regulate adipocyte production and secretion of
      fatty acids as well as glucose metabolism, resulting in increased insulin
      sensitivity in adipose tissue, liver, and skeletal muscle. However, TZDs have
      several adverse effects, including weight gain and liver toxicity. Herein we
      report identification of non-TZD PPARgamma agonists which exhibit beneficial
      effects similar to that of TZDs in animal models, but without the associated
      adverse effects.

PMID- 23142676
TI  - Experimental identification of small non-coding regulatory RNAs in the
      opportunistic human pathogen Burkholderia cenocepacia J2315.
AB  - Small non-coding regulatory RNAs (sRNAs) play important roles in regulating gene
      expression at the post-transcriptional level and often require the RNA chaperone
      Hfq. The human opportunistic pathogen Burkholderia cenocepacia J2315 encodes two
      distinct RNA chaperones, Hfq and Hfq2. The present work describes the
      experimental identification and validation of 24 sRNAs from B. cenocepacia J2315,
      based on the co-purification of sRNAs with the bacterium Hfq protein, followed by
      conversion into cDNA, cloning, computational analysis of sequences and validation
      by Northern blot analysis. The sRNAs here reported escaped identification by
      previous studies based on transcriptomics or bioinformatic analyses. Results
      presented indicate that 3 sRNAs are exclusive to bacteria of the Burkholderia
      cepacia complex and have no homologues in other bacteria, while the other 21
      share homology, at different extents, to sRNAs of other bacterial species. 

PMID- 23142677
TI  - Science requires the dispassionate presentation of information.

PMID- 23142678
TI  - Problems lie at several levels and bring into serious question the quality and
      standard of the editorial processes in your journal.

PMID- 23142679
TI  - Food and chemical toxicology.

PMID- 23142680
TI  - Re: Seralini, G.-E., et al. Long term toxicity of a Roundup herbicide and a
      Roundup-tolerant genetically modified maize. Food Chem. Toxicol. (2012).

PMID- 23142681
TI  - Assembly, stability and dynamics of virus capsids.
AB  - Most viruses use a hollow protein shell, the capsid, to enclose the viral genome.
      Virus capsids are large, symmetric oligomers made of many copies of one or a few
      types of protein subunits. Self-assembly of a viral capsid is a complex
      oligomerization process that proceeds along a pathway regulated by ordered
      interactions between the participating protein subunits, and that involves a
      series of (usually transient) assembly intermediates. Assembly of many virus
      capsids requires the assistance of scaffolding proteins or the viral nucleic
      acid, which interact with the capsid subunits to promote and direct the process.
      Once assembled, many capsids undergo a maturation reaction that involves covalent
      modification and/or conformational rearrangements, which may increase the
      stability of the particle. The final, mature capsid is a relatively robust
      protein complex able to protect the viral genome from physicochemical
      aggressions; however, it is also a metastable, dynamic structure poised to
      undergo controlled conformational transitions required to perform biologically
      critical functions during virus entry into cells, intracellular trafficking, and
      viral genome uncoating. This article provides an updated general overview on
      structural, biophysical and biochemical aspects of the assembly, stability and
      dynamics of virus capsids.

PMID- 23142683
TI  - The stability of 2-state, 3-state and more-state proteins from simple
      spectroscopic techniques... plus the structure of the equilibrium intermediates
      at the same time.
AB  - Protein stability is not just an academic matter. Biotechnology, Cell Biology and
      Drug Design are some of the fields where both theoretical and practical knowledge
      of protein stability is required. Simple equipment and chemicals, such as a
      thermostated fluorimeter and common denaturants, suffice to determine the
      conformational stability of a protein. To this end, the most important
      experiments are the preliminary ones done to establish the minimum number of
      species (conformations) accumulating in the equilibrium. For proteins with non
      functional equilibrium intermediates, determining the relevant stability of the
      protein (the free energy difference between the native conformation and the
      intermediate) is most important, and it allows very valuable structural
      information on the intermediate to be derived when protein variants are compared
      to wild type using equilibrium phi-analysis. The principles, tricks and equations
      involved in the analysis of denaturant induced or temperature induced equilibrium
      unfolding curves by the linear extrapolation method or using the integrated Gibbs
      Helmholtz equation, respectively, will be discussed, and a brief outline of
      challenges and frontiers in the protein stability field will be presented.

PMID- 23142682
TI  - Peroxynitrite formation in nitric oxide-exposed submitochondrial particles:
      detection, oxidative damage and catalytic removal by Mn-porphyrins.
AB  - Peroxynitrite (ONOO(-)) formation in mitochondria may be favored due to the
      constant supply of superoxide radical (O(2)(?-)) by the electron transport chain
      plus the facile diffusion of nitric oxide ((?)NO) to this organelle. Herein, a
      model system of submitochondrial particles (SMP) in the presence of succinate
      plus the respiratory inhibitor antimycin A (to increase O(2)(?-) rates) and the
      (?)NO-donor NOC-7 was studied to directly establish and quantitate peroxynitrite
      by a multiplicity of methods including chemiluminescence, fluorescence and
      immunochemical analysis. While all the tested probes revealed peroxynitrite at
      near stoichiometric levels with respect to its precursor radicals, coumarin
      boronic acid (a probe that directly reacts with peroxynitrite) had the more
      straightforward oxidation profile from O(2)(?-)-forming SMP as a function of the
      (?)NO flux. Interestingly, immunospintrapping studies verified protein radical
      generation in SMP by peroxynitrite. Substrate-supplemented SMP also reduced
      Mn(III)porphyrins (MnP) to Mn(II)P under physiologically-relevant oxygen levels
      (3-30 MUM); then, Mn(II)P were capable to reduce peroxynitrite and protect SMP
      from the inhibition of complex I-dependent oxygen consumption and protein radical
      formation and nitration of membranes. The data directly support the formation of
      peroxynitrite in mitochondria and demonstrate that MnP can undergo a catalytic
      redox cycle to neutralize peroxynitrite-dependent mitochondrial oxidative damage.

PMID- 23142684
TI  - The versatile role of gliadin peptides in celiac disease.
AB  - The link between the gluten component of wheat and celiac disease (CD) was
      discovered in 1952 by a team of physicians from Birmingham, England. Villous
      atrophy was described by John W. Paulley in 1954. During the 1960s, other
      features of CD were elucidated; its hereditary nature was recognized in 1965, and
      in 1966, dermatitis herpetiformis was linked to gluten sensitivity. Following the
      discovery of a link between gluten and CD, it was demonstrated that gliadin, one
      of the two principal protein groups comprising gluten, plays a critical role in
      CD. It has since become clear that the different and crucial roles of gliadin in
      CD result from its ability to activate multiple signaling pathways that modulate
      CD pathology. Most of these pathways involve the host innate and adaptive immune
      responses, but some pathways are activated when gliadin interacts with the
      intestinal cellular compartment. This review covers the current knowledge of the
      role of gliadin peptides in CD disorders that are characterized by
      intraepithelial T-cells infiltration (IEL), production of autoantibodies,
      endosomal trafficking, alteration of intestinal barrier function and intestinal
      cell proliferation. In addition, it examines the ability of these characteristics
      to determine the main clinicopathological features of gluten sensitivity for the
      purpose of identifying new strategies, other than maintaining a gluten-free diet,
      to improve the management of CD patients in the future.

PMID- 23142685
TI  - Rapid development of semistarvation-induced hyperactivity in Dark Agouti rats.
      Excessive wheel running and effect of 3,4-methylenedioxymethamphetamine (MDMA).
AB  - Clinical studies have found that patients with anorexia develop high activity
      levels. These data suggest a possible implication of activity in the aetiology of
      anorexia and are in line with findings obtained in animals during experimental
      procedures to model interactions between activity and weight loss. Activity-based
      anorexia (ABA) and semistarvation-induced hyperactivity (SIH) develop when
      laboratory rats have food access restricted to a single period in the day and are
      given free access to an activity wheel. This experiment sought to show the effect
      on weight loss of the excessive activity normally seen in Dark Agouti rats and of
      hyperactivity induced by 3,4-methylenedioxymethamphetamine (MDMA). To this end,
      32 female rats of the Dark Agouti strain were selected and divided into four
      groups in accordance with a 2 * 2 factorial design, in which one factor was
      treatment (saline or MDMA) and the other was access or lack of access to an
      activity wheel. Animals with wheel running access displayed a marked increase in
      running combined with accelerated weight loss. Although pharmacological treatment
      resulted in no observable effect on weight loss, rats treated with 12.5mg/kg MDMA
      generally registered more wheel running than did those treated with saline.
      Analysis of data on the temporal distribution of wheel running revealed an
      alteration in circadian activity patterns as a consequence of MDMA. These
      results, by showing a general high level of wheel running in Dark Agouti rats,
      once again emphasise the close relationship between activity and weight loss in
      the development of SIH and related phenomena such as ABA.

PMID- 23142686
TI  - Outcomes following radical cystectomy for nested variant of urothelial carcinoma:
      a matched cohort analysis.
AB  - PURPOSE: We evaluated oncological outcomes after radical cystectomy in patients
      with the nested variant of urothelial carcinoma and compared survival to that in
      patients with pure urothelial carcinoma of the bladder. MATERIALS AND METHODS: We
      identified 52 patients with the nested variant who were treated with radical
      cystectomy between 1980 and 2004. Pathological specimens were re-reviewed by a
      single genitourinary pathologist. Patients were matched 1:2 by age, gender, ECOG
      (Eastern Cooperative Oncology Group) performance status, pathological tumor stage
      and nodal status to patients with pure urothelial carcinoma. Survival was
      estimated using the Kaplan-Meier method and compared with the log rank test.
      RESULTS: Patients with the nested variant had a median age of 69.5 years (IQR 62,
      74) and a median postoperative followup of 10.8 years (IQR 9.3, 11.2). Nested
      variant cancer was associated with a high rate of adverse pathological features
      since 36 patients (69%) had pT3-T4 disease and 10 (19%) had nodal invasion. Eight
      patients (15%) with nested variant cancer received perioperative chemotherapy.
      When patients with the nested variant were matched to a cohort with pure
      urothelial carcinoma, no significant differences were noted in 10-year local
      recurrence-free survival (83% vs 80%, p = 0.46) or 10-year cancer specific
      survival (41% vs 46%, p = 0.75). CONCLUSIONS: The nested variant of urothelial
      carcinoma is associated with a high rate of locally advanced disease at radical
      cystectomy. However, when stage matched to patients with pure urothelial
      carcinoma, patients with the nested variant did not have an increased rate of
      recurrence or adverse survival. Further studies are required to validate these
      findings and guide the optimal multimodal treatment approach to these patients.

PMID- 23142687
TI  - Aspiration and sclerotherapy: a nonsurgical treatment option for hydroceles.
AB  - PURPOSE: We demonstrated that hydrocele aspiration and sclerotherapy with
      doxycycline is an effective and safe nonsurgical treatment option for hydrocele
      correction. MATERIALS AND METHODS: The medical records of patients who underwent
      hydrocele aspiration and sclerotherapy were analyzed in a retrospective cohort
      study for success rates as well as improvement in scrotal size and discomfort
      after a single hydrocele aspiration and sclerotherapy treatment. Patients who
      reported decreased scrotal size, improved physical symptoms and satisfaction with
      the procedure were considered as having success with hydrocele aspiration and
      sclerotherapy. RESULTS: A total of 29 patients (mean age 52.8 years) presenting
      with 32 nonseptated hydroceles underwent hydrocele aspiration and sclerotherapy
      with doxycycline between 2005 and 2012. Of the hydroceles 27 (84%) were
      successfully treated with a single aspiration and sclerotherapy procedure.
      Overall mean followup was 20.8 months. Three patients reported moderate pain
      which resolved in 2 to 3 days. Of those patients in whom hydrocele aspiration and
      sclerotherapy failed, 1 had hydrocele successfully resolved with a second
      aspiration and sclerotherapy treatment, 3 did not have success with a second
      procedure and underwent hydrocelectomy, and 1 wanted immediate surgical
      correction. CONCLUSIONS: Hydrocele aspiration and sclerotherapy was successful in
      correcting 84% of simple nonseptated hydroceles with a single treatment. This
      result is an increase from previously reported success rates involving a single
      hydrocele aspiration and sclerotherapy procedure with tetracycline (75%). The
      success rate of a single hydrocele aspiration and sclerotherapy procedure is
      similar to the reported success rates involving hydrocelectomy while avoiding the
      hospital expense and many other complications. We conclude that the hydrocele
      aspiration and sclerotherapy procedure is a reasonable, nonsurgical and underused
      treatment option for nonseptated simple hydroceles.

PMID- 23142688
TI  - Re: does partial cystectomy compromise oncologic outcomes for patients with
      bladder cancer compared to radical cystectomy? A matched case-control analysis.

PMID- 23142689
TI  - FDG-positron emission tomography/computerized tomography for monitoring the
      response of pelvic lymph node metastasis to neoadjuvant chemotherapy for bladder
      cancer.
AB  - PURPOSE: We evaluated FDG-positron emission tomography/computerized tomography
      for monitoring the response of pelvic lymph node metastasis to neoadjuvant
      chemotherapy for bladder cancer. We compared this to contrast enhanced
      computerized tomography. MATERIALS AND METHODS: Included in study were 19
      consecutive patients with lymph node positive bladder cancer who underwent FDG
      positron emission tomography/computerized tomography and contrast enhanced
      computerized tomography before and after a median of 4 cycles (range 2 to 4) of
      neoadjuvant chemotherapy between September 2011 and April 2012. Metabolic
      response was assessed according to EORTC (European Organisation for Research and
      Treatment of Cancer) recommendations based on the change in FDG uptake on FDG
      positron emission tomography/computerized tomography. Radiological response was
      assessed on contrast enhanced computerized tomography according to RECIST
      (Response Evaluation Criteria in Solid Tumors) 1.1. All patients underwent pelvic
      lymph node dissection. Histopathological evaluation served as the gold standard
      for the nodal response. RESULTS: Before neoadjuvant chemotherapy, hypermetabolic
      FDG uptake was seen in all 19 patients, which matched the lymph node metastasis.
      Evaluating the nodal response with positron emission tomography/computerized
      tomography was feasible in all patients. On histopathology 16 patients were
      responders, including 14 with a complete pathological response of the lymph
      nodes. Positron emission tomography/computerized tomography and contrast enhanced
      computerized tomography correctly distinguished responders from nonresponders (18
      of 19 patients or 94.7% and 15 of 19 or 78.9%) and complete responders from
      patients with residual disease (13 of 19 or 68.4% and 12 of 19 or 63.2%,
      respectively). CONCLUSIONS: Although no definitive conclusions can be drawn from
      these preliminary data, positron emission tomography/computerized tomography
      appears feasible for evaluating the nodal response to neoadjuvant chemotherapy
      and distinguishing responders from nonresponders.

PMID- 23142690
TI  - FGFR3 mutation analysis in voided urine samples to decrease cystoscopies and cost
      in nonmuscle invasive bladder cancer surveillance: a comparison of 3 strategies.
AB  - PURPOSE: We determined whether FGFR3 mutation analysis of voided urine samples
      would be cost-effective to partly replace cystoscopy in the surveillance of
      patients treated for nonmuscle invasive urothelial carcinoma. MATERIALS AND
      METHODS: In this decision analytical study we analyzed data on 70 Dutch patients
      with FGFR3 positive primary tumors and a median followup of 8.8 years.
      Surveillance strategies were compared in a Markov model. Modified surveillance
      consisted of FGFR3 mutation analysis of voided urine samples every 3 months, and
      cystoscopy at 3, 12 and 24 months. Standard surveillance was defined as
      cystoscopy every 3 months and minimal surveillance was defined as cystoscopy at
      3, 12 and 24 months. Analysis was stratified for 3 risk profiles, including
      surveillance after 1) the primary tumor, 2) the first to third recurrence and 3)
      the fourth recurrence or more. Sensitivity analysis was performed to evaluate the
      impact of variations in cost, sensitivity and specificity. RESULTS: The
      probability of no recurrence after 2 years of surveillance after a primary tumor
      was higher for modified surveillance than for standard and minimal surveillance,
      eg after primary tumors (95.7% vs 95.0% and 93.9%, respectively). The total cost
      of surveillance after the primary tumor was lower for minimal and modified
      surveillance (?2,254 and ?2,558, respectively) than for standard surveillance
      (?5,861). Results were robust to changing inputs over plausible ranges and
      consistent for each of the 3 risk profiles. CONCLUSIONS: Surveillance in which
      cystoscopy is partly replaced by FGFR3 mutation analysis of urine seems a safe,
      effective and cost-effective surveillance strategy. Further validation in larger
      cohorts is required.

PMID- 23142691
TI  - Premature ejaculation results in female sexual distress: standardization and
      validation of a new diagnostic tool for sexual distress.
AB  - PURPOSE: We measured premature ejaculation related female sexual distress using a
      new diagnostic tool, the Female Sexual Distress Scale-Revised-Premature
      Ejaculation questionnaire. MATERIALS AND METHODS: In this large-scale, Internet
      based population study we evaluated 2,109 women in a stable relationship during
      the last 6 months. The 1,361 women in the premature ejaculation group had no
      female sexual disorder but the partner had premature ejaculation alone. The 748
      controls had no female sexual disorder and a partner without premature
      ejaculation. We determined questionnaire content and discriminant validity,
      internal consistency and test-retest reliability. Multivariate logistic
      regression with propensity score reweighting was done to determine the clinical
      impact of demographics on the perception of sexual distress. RESULTS: The
      questionnaire was well understood. Internal consistency was greater than 0.90 and
      0.84 in the premature ejaculation and control groups, respectively. Test-retest
      reliability was 0.82 (95% CI 0.72-0.87) and 0.85 (95% CI 0.79-0.92) in the
      premature ejaculation and control groups, respectively. The questionnaire had a
      high AUC of 0.90 (95% CI 0.89-0.91). The new cutoff score of 12 or greater had
      79.1% sensitivity (95% CI 73.8-82.5), 99.5% specificity (95% CI 98.0-100.0),
      99.3% positive predictive value (95% CI 98.7-100.0) and 67.9% negative predictive
      value (95% CI 64.2-73.2). Median questionnaire scores were significantly higher
      in the premature ejaculation group than in controls (20, 95% CI 19-21 vs 6, 95%
      CI 6-7, p <0.0001). Logistic regression adjusted and unadjusted by propensity
      score indicated that women in the premature ejaculation group had a 7.12 (95% CI
      5.98-10.14, p <0.0001) to 9.83 (95% CI 7.94-12.15) greater probability of sexual
      distress than controls. CONCLUSIONS: The Female Sexual Distress Scale-Revised
      Premature Ejaculation questionnaire fulfills psychometric requirements for
      measuring sexual distress related to partner sexual dysfunction.

PMID- 23142692
TI  - Xanthine oxidase and lens oxidative stress markers in diabetic and senile
      cataract patients.
AB  - Xanthine oxidase (XOD) is a prooxidant enzyme possibly implicated in diabetic
      lens injury and genesis of senile cataract (SC). We evaluated the impact of
      diabetes on XOD activity and its relationships with lens oxidative stress markers
      in patients operated on for SC. Serum and lens XOD activities, lens
      malondialdehyde (MDA), conjugated dienes, superoxide dismutase (SOD), glutathione
      peroxidase (GPx) and reduced glutathione (GSH) levels were measured in 62 non
      diabetic and 29 diabetic patients operated on for SC. Lens XOD, SOD, GPx and GSH
      levels were gradually declining, while MDA and serum XOD were increasing with
      patient's age. Lens XOD activity was positively correlated with conjugated dienes
      concentration (rho=0.316; p=0.003) while being inversely correlated with age
      (rho=-0.371; p<0.001), indicating that low ocular expression of XOD could be
      related to lower intensity of oxidative stress and delayed occurrence of SC. When
      samples were adjusted for confounding factors, serum XOD (p<0.001), lens XOD
      (p=0.003) and conjugated dienes (p=0.002) were significantly higher in diabetic
      than in non-diabetic group. Lens SOD and GPx were moderately increased while MDA
      and GSH were unchanged in diabetic, compared with non-diabetic SC group. Blood
      HbA1C concentration was positively correlated with lens XOD (rho=0.346; p<0.001)
      as well as serum XOD activity (rho=0.485; p<0.001). These results suggest that
      poor glycemic control may upregulate systemic and ocular XOD activities
      contributing to lens oxidative stress and possibly to earlier onset of cataract.

PMID- 23142693
TI  - Propose but verify: fast mapping meets cross-situational word learning.
AB  - We report three eyetracking experiments that examine the learning procedure used
      by adults as they pair novel words and visually presented referents over a
      sequence of referentially ambiguous trials. Successful learning under such
      conditions has been argued to be the product of a learning procedure in which
      participants provisionally pair each novel word with several possible referents
      and use a statistical-associative learning mechanism to gradually converge on a
      single mapping across learning instances [e.g., Yu, C., & Smith, L. B. (2007).
      Rapid word learning under uncertainty via cross-situational statistics.
      Psychological Science, 18(5), 414-420]. We argue here that successful learning in
      this setting is instead the product of a one-trial procedure in which a single
      hypothesized word-referent pairing is retained across learning instances,
      abandoned only if the subsequent instance fails to confirm the pairing--more a
      'fast mapping' procedure than a gradual statistical one. We provide experimental
      evidence for this propose-but-verify learning procedure via three experiments in
      which adult participants attempted to learn the meanings of nonce words cross
      situationally under varying degrees of referential uncertainty. The findings,
      using both explicit (referent selection) and implicit (eye movement) measures,
      show that even in these artificial learning contexts, which are far simpler than
      those encountered by a language learner in a natural environment, participants do
      not retain multiple meaning hypotheses across learning instances. As we discuss,
      these findings challenge 'gradualist' accounts of word learning and are
      consistent with the known rapid course of vocabulary learning in a first
      language.

PMID- 23142694
TI  - ALK2 and BMPR2 knockdown and endothelin-1 production by pulmonary microvascular
      endothelial cells.
AB  - BACKGROUND: Many cases of pulmonary arterial hypertension (PAH) are heritable and
      related to gene mutations in bone morphogenic receptor-2 (BMPR2). These patients
      consequently may have a signaling imbalance within the transforming growth factor
      beta (TGFbeta) receptor superfamily. The causes of increased endothelin-1 (ET-1),
      which contributes to PAH, are unknown, and we therefore studied the contribution
      of various BMPs and their receptors on ET-1 production in vitro, after knockdown
      of BMPR2 in human pulmonary microvascular endothelial cells (HMVEC-LBl).
      METHODOLOGY/PRINCIPAL FINDINGS: Receptor knockdown in HMVEC-LBl was performed
      using siRNA to BMPR2, and activin like-kinases 1 and 2 (ALK1, ALK2). ET-1 and
      TGFbeta levels in the medium were measured by ELISA. In some experiments, cells
      were exposed to TGFbeta or BMP7 or FK506 (tacrolimus). Using Western blotting,
      levels of BMPR2, endothelin ET(B) receptor, phosphorylated SMAD 2 (pSMAD 2),
      phosphorylated SMAD 1,5 (pSMAD 1,5), ALK1, ALK2, ALK5, TGFbeta receptor 2,
      plasminogen activator inhibitor-1 (PAI-1) and ID1 were measured. BMPR2 knockdown
      significantly increased ET-1 levels. It did not affect ET(B) receptor or TGFbeta
      levels. TGFbeta increased ET-1 levels, with or without BMPR2 knockdown. BMPR2
      knockdown did not affect TGFbeta (pSMAD 2 and PAI-1) signaling. BMP7 increased ET
      1 levels after BMPR2 knockdown but this was prevented by ALK2 knockdown as was
      the increase in ID1 caused by BMPR2 knockdown. FK506, which interacts with ALK2,
      increased ET-1 levels and ID1 levels, and this was blocked by ALK2 knockdown.
      CONCLUSION/SIGNIFICANCE: ALK2 may be an important receptor in ET-1 production
      during BMPR2 knockdown.

PMID- 23142695
TI  - Extraordinary micro-endemism in Australian desert spring amphipods.
AB  - Increasing pressure for water in the Australian arid zone is placing enormous
      stress on the diverse endemic communities inhabiting desert springs. Detailed
      information about the evolutionary processes occurring within and between
      individual endemic species will help to develop effective and biologically
      relevant management strategies this fragile ecosystem. To help determine
      conservation priorities, we documented the genetic structure of the endemic
      freshwater amphipod populations in springs fed by the Great Artesian Basin in
      central Australia. Phylogenetic and phylogeographic history and genetic diversity
      measures were examined using nuclear and mitochondrial DNA from approximately 500
      chiltoniid amphipods across an entire group of springs. Pronounced genetic
      diversity was identified, demonstrating that levels of endemism have been grossly
      underestimated in these amphipods. Using the GMYC model, 13 genetically divergent
      lineages were recognized as Evolutionarily Significant Units (ESUs), all of which
      could be considered as separate species. The results show that due to the highly
      fragmented ecosystem, these taxa have highly restricted distributions. Many of
      the identified ESUs are endemic to a very small number of already degraded
      springs, with the rarest existing in single springs. Despite their
      extraordinarily small ranges, most ESUs showed relative demographic stability and
      high levels of genetic diversity, and genetic diversity was not directly linked
      to habitat extent. The relatively robust genetic health of ESUs does not preclude
      them from endangerment, as their limited distributions ensure they will be highly
      vulnerable to future water extraction.

PMID- 23142696
TI  - Fourfold paralogy regions on human HOX-bearing chromosomes: role of ancient
      segmental duplications in the evolution of vertebrate genome.
AB  - BACKGROUND: Susumu Ohno's idea that modern vertebrates are degenerate polyploids
      (concept referred as 2R hypothesis) has been the subject of intense debate for
      past four decades. It was proposed that intra-genomic synteny regions
      (paralogons) in human genome are remains of ancient polyploidization events that
      occurred early in the vertebrate history. The quadruplicated paralogon centered
      on human HOX clusters is taken as evidence that human HOX-bearing chromosomes
      were structured by two rounds of whole genome duplication (WGD) events. RESULTS:
      Evolutionary history of human HOX-bearing chromosomes (chromosomes 2/7/12/17) was
      evaluated by the phylogenetic analysis of multigene families with triplicated or
      quadruplicated distribution on these chromosomes. Topology comparison approach
      categorized the members of 44 families into four distinct co-duplicated groups.
      Distinct gene families belonging to a particular co-duplicated group, exhibit
      similar evolutionary history and hence have duplicated simultaneously, whereas
      genes of two distinct co-duplicated groups do not share their evolutionary
      history and have not duplicated in concert with each other. CONCLUSION: The
      recovery of co-duplicated groups suggests that "ancient segmental duplications
      and rearrangements" is the most rational model of evolutionary events that have
      generated the triplicated and quadruplicated paralogy regions seen on the human
      HOX-bearing chromosomes.

PMID- 23142697
TI  - Genetic aspects of mitochondrial genome evolution.
AB  - Many years of extensive studies of metazoan mitochondrial genomes have
      established differences in gene arrangements and genetic codes as valuable
      phylogenetic markers. Understanding the underlying mechanisms of replication,
      transcription and the role of the control regions which cause e.g. different gene
      orders is important to assess the phylogenetic signal of such events. This review
      summarises and discusses, for the Metazoa, the general aspects of mitochondrial
      transcription and replication with respect to control regions as well as several
      proposed models of gene rearrangements. As whole genome sequencing projects
      accumulate, more and more observations about mitochondrial gene transfer to the
      nucleus are reported. Thus occurrence and phylogenetic aspects concerning nuclear
      mitochondrial-like sequences (NUMTS) is another aspect of this review.

PMID- 23142698
TI  - A molecular phylogeny of the lizard genus Phymaturus (Squamata, Liolaemini):
      implications for species diversity and historical biogeography of southern South
      America.
AB  - The lizard genus Phymaturus is widely distributed in Argentina and along the
      eastern edge of Chile between 25 degrees  and 45 degrees  south. We sampled 27 of
      the 38 currently recognized species plus 22 candidate species using two
      mitochondrial genes (cytb and 12S), four protein coding nuclear genes and seven
      anonymous nuclear loci, and present the first comprehensive molecular
      phylogenetic hypothesis for the clade. We recovered two large clades (the palluma
      or northern group and patagonicus or southern group) previously recognized on the
      basis of morphological and mitochondrial sequence evidence, and compared results
      obtained from concatenated-gene analyses with results of a coalescent-based
      species-tree approach (BEST). With both methods we identified four main clades
      within the palluma group (mallimaccii, roigorum, verdugo, and vociferator) and
      five main clades within the patagonicus group (calcogaster, indistinctus,
      payuniae, somuncurensis, and spurcus). We found several instances of non
      monophyly with cytb and cases of incongruence between mitochondrial vs nuclear
      data for which we discuss alternative hypotheses. Although with lower support
      values, combined BEST results are more congruent with concatenated nuclear data
      than with combined concatenated analyses, suggesting that BEST is less influenced
      by demographic processes than combined concatenated analyses. We discuss the
      taxonomic, biogeographic and conservation implications of these results and how
      the future integration of phylogeographic and morphological approaches will allow
      the further testing of demographic and biogeographic hypotheses.

PMID- 23142699
TI  - Proto-oncogene PIM-1 is a novel estrogen receptor target associating with high
      grade breast tumors.
AB  - We searched ERalpha cistromes of MCF-7 breast cancer cells for previously
      unrecognized ERalpha targets and identified proto-oncogene PIM-1 as a novel
      potential target gene. We show that the expression of PIM-1 is induced in
      response to estradiol in MCF-7 cells and that the induction is mediated by
      ERalpha-regulated enhancers located distally upstream from the gene. In keeping
      with the growth-promoting role of the PIM-1, depletion of the PIM-1 attenuated
      the proliferation of the MCF-7 cells, which was paralleled with up-regulation of
      cyclin-dependent protein kinase inhibitor CDKN1A and CDKN2B expression. Analysis
      of PIM-1 expression between invasive breast tumors and benign breast tissue
      samples showed that elevated PIM-1 expression is associated with malignancy and a
      higher tumor grade. In sum, identification of PIM-1 as an ERalpha target gene
      adds a novel potential mechanism by which estrogens can contribute to breast
      cancer cell proliferation and carcinogenesis.

PMID- 23142700
TI  - Expression and regulation of transient receptor potential cation channel,
      subfamily M, member 2 (TRPM2) in human endometrium.
AB  - To identify estrogen-responsive genes, we previously isolated estrogen receptor
      (ER)-binding DNA fragments from human genomic DNA using a recombinant ER protein.
      Six DNA fragments, each including a perfect palindromic estrogen response element
      (ERE), were obtained. The nucleotide sequence of one of the six fragments (E1
      fragment) showed that the ERE of the E1 fragment is located in the 3'
      untranslated region (UTR) of transient receptor potential cation channel,
      subfamily M, member 2 (TRPM2). Here, we confirmed the estrogen-dependent enhancer
      activity of the ERE of the E1 fragment by chloramphenicol acetyltransferase
      assay. TRPM2 mRNA expression was investigated in human endometrium, cultured
      human endometrial stromal cells (ESCs), and cultured human endometrial epithelial
      cells (EECs) using RT-PCR. Quantitative RT-PCR revealed that TRPM2 mRNA
      expression in ESCs increased after 17beta-estradiol (E2) treatment. This study
      demonstrated for the first time that TRPM2 is an estrogen-responsive gene
      expressed in human endometrial cells.

PMID- 23142701
TI  - Comparative RNA-sequencing of the acarbose producer Actinoplanes sp. SE50/110
      cultivated in different growth media.
AB  - Actinoplanes sp. SE50/110 is known as the producer of the alpha-glucosidase
      inhibitor acarbose, a potent drug in the treatment of type-2 diabetes mellitus.
      We conducted the first whole transcriptome analysis of Actinoplanes sp. SE50/110,
      using RNA-sequencing technology for comparative gene expression studies between
      cells grown in maltose minimal medium, maltose minimal medium with trace
      elements, and glucose complex medium. We first studied the behavior of
      Actinoplanes sp. SE50/110 cultivations in these three media and found that the
      different media had significant impact on growth rate and in particular on
      acarbose production. It was demonstrated that Actinoplanes sp. SE50/110 grew well
      in all three media, but acarbose biosynthesis was only observed in cultures grown
      in maltose minimal medium with and without trace elements. When comparing the
      expression profiles between the maltose minimal media with and without trace
      elements, only few significantly differentially expressed genes were found, which
      mainly code for uptake systems of metal ions provided in the trace element
      solution. In contrast, the comparison of expression profiles from maltose minimal
      medium and glucose complex medium revealed a large number of differentially
      expressed genes, of which the most conspicuous genes account for iron storage and
      uptake. Furthermore, the acarbose gene cluster was found to be highly expressed
      in maltose-containing media and almost silent in the glucose-containing medium.
      In addition, a putative antibiotic biosynthesis gene cluster was found to be
      similarly expressed as the acarbose cluster. 

PMID- 23142702
TI  - Preparation of an adipogenic hydrogel from subcutaneous adipose tissue.
AB  - The ability to generate controlled amounts of adipose tissue would greatly ease
      the burden on hospitals for reconstructive surgery. We have previously shown that
      a tissue engineering chamber containing a vascular pedicle was capable of forming
      new fat; however, further refinements are required to enhance fat formation. The
      development and maintenance of engineered adipose tissue requires a suitable
      source of growth factors and a suitable scaffold. A hydrogel derived from adipose
      tissue may fulfil this need. Subcutaneous fat was processed into a
      thermosensitive hydrogel we refer to as adipose-derived matrix (ADM). Protein
      analysis revealed high levels of basement membrane proteins, collagens and
      detectable levels of growth factors. Adipose-derived stem cells exposed to this
      hydrogel differentiated into adipocytes with >90% efficiency and in vivo testing
      in rats showed significant signs of adipogenesis after 8 weeks. ADM's adipogenic
      properties combined with its simple gelation, relatively long shelf life and its
      tolerance to multiple freeze-thaw cycles, makes it a promising candidate for
      adipose engineering applications.

PMID- 23142703
TI  - An assignment of intrinsically disordered regions of proteins based on NMR
      structures.
AB  - Intrinsically disordered proteins (IDPs) do not adopt stable three-dimensional
      structures in physiological conditions, yet these proteins play crucial roles in
      biological phenomena. In most cases, intrinsic disorder manifests itself in
      segments or domains of an IDP, called intrinsically disordered regions (IDRs),
      but fully disordered IDPs also exist. Although IDRs can be detected as missing
      residues in protein structures determined by X-ray crystallography, no protocol
      has been developed to identify IDRs from structures obtained by Nuclear Magnetic
      Resonance (NMR). Here, we propose a computational method to assign IDRs based on
      NMR structures. We compared missing residues of X-ray structures with residue
      wise deviations of NMR structures for identical proteins, and derived a threshold
      deviation that gives the best correlation of ordered and disordered regions of
      both structures. The obtained threshold of 3.2A was applied to proteins whose
      structures were only determined by NMR, and the resulting IDRs were analyzed and
      compared to those of X-ray structures with no NMR counterpart in terms of
      sequence length, IDR fraction, protein function, cellular location, and amino
      acid composition, all of which suggest distinct characteristics. The structural
      knowledge of IDPs is still inadequate compared with that of structured proteins.
      Our method can collect and utilize IDRs from structures determined by NMR,
      potentially enhancing the understanding of IDPs.

PMID- 23142705
TI  - Increased resistance of immobilized-stressed mice to infection: correlation with
      behavioral alterations.
AB  - Immobilization is an easy and convenient method to induce both psychological and
      physical stress resulting in restricted motility and aggression and is believed
      to be the most severe type of stress in rodent models. Although it has been
      generally accepted that chronic stress often results in immunosuppression while
      acute stress has been shown to enhance immune responses, the effects of IS on the
      host resistance to Escherichia coli (E. coli) infection and associated behavioral
      changes are still not clear. In a series of experiments aimed at determining the
      level of hypothalamic COX-2, HSP-90, HSP-70, SOD-1 and plasma level of
      corticosterone, cytokine, antibody titer and their association with behavioral
      activities, mice were infected with viable E. coli during acute and chronic IS by
      taping their paws. In this study we show that acute and chronic IS enhances the
      resistance of mice to E. coli infection via inhibiting the production of pro
      inflammatory cytokines, free radicals, and by improving the exploratory behavior.
      Altogether, our findings support the notion that cytokines released during immune
      activation and under the influence of corticosterone can modulate the open field
      behavior both in terms of locomotor activity as well as exploration. One of the
      features observed with chronic stressor was a lower ability to resist bacterial
      infection, although in case of acute stress, a better clearance of bacterial
      infection was observed in vivo with improvement of exploratory behavior and
      cognitive functions.

PMID- 23142704
TI  - Socioeconomic factors and leukocyte telomere length in a multi-ethnic sample:
      findings from the multi-ethnic study of atherosclerosis (MESA).
AB  - Previous findings have linked lower socioeconomic status (SES) with elevated
      morbidity and mortality. Leukocyte telomere length (LTL), which also has been
      associated with age-related disease morbidity and mortality, is a marker of aging
      at the cellular level, making it a valuable early biomarker of risk and an
      indicator of biological age. It is hypothesized that SES will be associated with
      LTL, indicating that SES influences disease risk by accelerating biological
      aging. In the present sample we test for associations of childhood SES and adult
      SES (i.e. education, income, home ownership) with LTL, and examine whether these
      associations vary by racial/ethnic group. Analyses on 963 subjects (18.7% White,
      53% Hispanics, and 28.5% African American) from the stress ancillary study of the
      multi-ethnic study of atherosclerosis revealed a significant difference in LTL
      between home owners and renters in Hispanic and White participants (p<.05), but
      not amongst African Americans (p=.98). There were no linear associations of adult
      education or family income with LTL, however, there was an inverse association
      between father's education and LTL (p=.03). These findings suggest that for
      Whites and Hispanics renting vs. owning a home is associated with an older
      biological age; however we did not replicate previous findings linking education
      with LTL.

PMID- 23142706
TI  - The effects of rTMS over the primary motor cortex: the link between action and
      language.
AB  - Is the primary motor cortex (M1) necessary for language comprehension? The
      present study investigates the role of the primary motor cortex during verbs
      comprehension, within the framework of the embodied theories of language. We
      applied rTMS over the right and left hand portion of M1 and tested the effects of
      the stimulation toward the processing of hand-related action verbs versus
      abstract verbs. Results underlined a specific inhibition effect following left
      stimulation, only with hand-related action verbs. These findings seem to
      corroborate the hypothesis of a functional role of M1 in action verbs
      comprehension.

PMID- 23142707
TI  - When more is less: increasing allocentric visual information can switch visual
      proprioceptive combination from an optimal to sub-optimal process.
AB  - When reaching for an object in the environment, the brain often has access to
      multiple independent estimates of that object's location. For example, if someone
      places their coffee cup on a table, then later they know where it is because they
      see it, but also because they remember how their reaching limb was oriented when
      they placed the cup. Intuitively, one would expect more accurate reaches if
      either of these estimates were improved (e.g., if a light were turned on so the
      cup were more visible). It is now well-established that the brain tends to
      combine two or more estimates about the same stimulus as a maximum-likelihood
      estimator (MLE), which is the best thing to do when estimates are unbiased. Even
      in the presence of small biases, relying on the MLE rule is still often better
      than choosing a single estimate. For this work, we designed a reaching task in
      which human subjects could integrate proprioceptive and allocentric (landmark
      relative) visual information to reach for a remembered target. Even though both
      of these modalities contain some level of bias, we demonstrate via simulation
      that our subjects should use an MLE rule in preference to relying on one modality
      or the other in isolation. Furthermore, we show that when visual information is
      poor, subjects do, indeed, combine information in this way. However, when we
      improve the quality of visual information, subjects counter-intuitively switch to
      a sub-optimal strategy that occasionally includes reliance on a single modality.

PMID- 23142708
TI  - The diagnostic value of urinary incontinence in the differential diagnosis of
      seizures.
AB  - PURPOSE: Urinary incontinence may occur both in epileptic seizures (ES) and in
      non-epileptic events (NEE) such as psychogenic nonepileptic events (PNEEs) and
      syncope. A comprehensive search of the literature to determine the accuracy of
      this physical finding and its prevalence in epileptic seizures and syncope is
      still lacking. To undertake a systematic review to determine sensitivity,
      specificity and likelihood ratios (LR) of urinary incontinence in the
      differential diagnosis between ES and NEEs (including syncope and PNEEs).
      METHODS: Studies evaluating the presence of urinary incontinence in ES and NEEs
      were systematically searched. Sensitivity, specificity, positive and negative
      likelihood ratio (pLR, nLR) of incontinence were determined for each study and
      for the pooled results. RESULTS: Five studies (221 epilepsy patients and 252
      subjects with NEEs) were included. Pooled accuracy measures of urinary
      incontinence (ES versus NEEs) were: sensitivity 38%, specificity 57%, pLR 0.879
      (95% CI 0.705-1.095) and nLR 1.092 (95% CI 0.941-1.268). For each comparison
      (epileptic seizures versus NEEs; ES versus syncope; ES versus PNEEs), pooled
      accuracy measures for urinary incontinence showed a statistically not significant
      pLR (the 95% CI of the pooled value included 1, and the LR value of 1 has no
      discriminatory value). CONCLUSIONS: A pooled analysis of data from the literature
      shows that urinary incontinence has no value either in the differential
      diagnostic between ES and syncope/PNEEs. Systematic reviews with pooled analyses
      of data from the literature allow an increase in statistical power and an
      improvement in precision, representing a useful tool to determine the accuracy of
      a certain physical finding in the differential diagnosis between ES and other
      paroxysmal events.

PMID- 23142709
TI  - Antiepileptic drug use in Austrian nursing home residents.
AB  - PURPOSE: Currently around 30% of all newly developed seizures are diagnosed in
      persons older than 65 years. Five to 17% of nursing home-residents take
      antiepileptic drugs. The aim of our study was to analyze the type and frequency
      of prescribed antiepileptic drugs, as well as their indication, co-morbidities
      and co-medications in institutionalized elderly in Austria. METHODS: This was a
      retrospective, cross-sectional study, which included all residents of the seven
      public nursing homes in Innsbruck, Austria. The data of 828 probands were
      extracted from the charts at site and maintained anonymously. The data collection
      was followed by descriptive statistics. KEY FINDINGS: 70 (8.5%; 26 M/44 F) of the
      828 (192 M/636 F) residents took at least one antiepileptic medication. In 51.5%
      the reason for the prescription were epileptic seizures - yielding a minimum
      prevalence of 4.5%. The most often used antiepileptic drugs were gabapentin
      (37%), levetiracetam (24%) and valproate (18.5%). The three most common co
      morbidities were arterial hypertension (49%), ischemic stroke (36%) and other
      cerebrovascular diseases (29%). Six to nine co-medications were prescribed in
      41%, 26% had more than 10 additional drugs and 91% were treated with
      proconvulsive co-medications (64/70, median 2, range 0-6). SIGNIFICANCE: Austrian
      nursing home residents receive more frequently newer antiepileptic drugs compared
      to other countries, but co-prescription of proconvulsive drugs is common.

PMID- 23142710
TI  - Superoxide anion mediates the L-selectin down-regulation induced by non-steroidal
      anti-inflammatory drugs in human neutrophils.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) induce the shedding of L-selectin
      in human neutrophils through a mechanism still not well understood. In this work
      we studied both the functional effect of NSAIDs on the neutrophils/endothelial
      cells dynamic interaction, and the potential involvement of reactive oxygen
      species (ROS) in the NSAIDs-mediated down-regulation of L-selectin. When human
      neutrophils were incubated with diclofenac, a significant reduction in the number
      of cells that rolled on activated endothelial cells was observed. Different
      NSAIDs (flufenamic acid, meclofenamic acid, diclofenac, indomethacin, nimesulide,
      flurbiprofen, meloxicam, phenylbutazone, piroxicam, ketoprofen and aspirin)
      caused variable increase in neutrophil intracellular ROS concentration, which was
      inversely proportional to the change produced in L-selectin surface expression.
      Pre-incubation of neutrophils with superoxide dismutase, but not with catalase,
      showed both a significant protective effect on the L-selectin down-regulation
      induced by several NSAIDs and a diminished effect of diclofenac on neutrophil
      rolling. Interestingly, diclofenac and flufenamic acid but not piroxicam
      significantly increased the extracellular superoxide anion production by
      neutrophils, and inhibition of nicotinamide adenine dinucleotide phosphate
      (NADPH)-oxidase activity with diphenyleneiodonium prevented the down-regulation
      of L-selectin by diclofenac. In accordance with these results, neutrophils from
      patients with chronic granulomatous disease, a hereditary disease in which
      neutrophils show a reduced capacity to form superoxide radicals, exhibited a
      lower down-regulation of L-selectin (IC50: 15.3 MUg/ml) compared to normal
      controls (IC50: 5.6 MUg/ml) in response to diclofenac. CONCLUSION: A group of
      NSAIDs is capable of interfering with the ability of neutrophils to interact with
      endothelial cells by triggering L-selectin-shedding through the NADPH-oxidase
      dependent generation of superoxide anion at the plasma membrane.

PMID- 23142712
TI  - Yuwen02f1 suppresses LPS-induced endotoxemia and adjuvant-induced arthritis
      primarily through blockade of ROS formation, NFkB and MAPK activation.
AB  - Phagocytes release inflammatory mediators to defense harmful stimuli upon
      bacterial invasion, however, excessive inflammatory reaction leads to tissue
      damage and manifestation of pathological states. Therefore, targeting on
      uncontrolled inflammation seems feasible to control numerous inflammation
      associated diseases. Under the drug screening process of synthetic
      diphenylpyrazole derivatives, we discovered compound yuwen02f1 possesses anti
      inflammatory effects in decreasing the release of pro-inflammatory cytokines
      including TNFalpha and IL-6, nitric oxide, reactive oxygen species (ROS) as well
      as inhibiting migration of LPS-stimulated phagocytes. In addition, we observed
      that the molecular mechanism of yuwen02f1-mediated anti-inflammation is
      associated with decreasing phosphorylation of MAPK molecules including ERK1/2,
      JNK and p38, and attenuating translocation of p47(phox) and p67(phox) to the cell
      membrane. Yuwen02f1 also reverses IkappaBalpha degradation and attenuates the
      expression of NFkappaB-related downstream inducible enzymes like iNOS and COX-2.
      Furthermore, we found that yuwen02f1 attenuates some pathological syndromes of
      LPS-induced sepsis and adjuvant-induced arthritis in mice, as evidenced by
      decreasing the cytokine production, reversing thrombocytopenic syndrome,
      protecting the mice from tissue injury in septic mice, and attenuating paw edema
      in arthritic mice as well. These results suggest that yuwen02f1 is a potential
      anti-inflammatory agent for alleviating syndromes of acute and chronic
      inflammatory diseases as evidenced by attenuating the generation of cytokines and
      down-regulating the expression of iNOS and COX-2 through the blockade of ROS
      generation and NADPH oxidase, NFkappaB and MAPK activation pathways in LPS
      stimulated phagocytes.

PMID- 23142711
TI  - Proteasome inhibition attenuates heart failure during the late stages of pressure
      overload through alterations in collagen expression.
AB  - Although the role of the ubiquitin-proteasome system (UPS) in cardiac hypertrophy
      induced by pressure overload has been consistently studied, the fundamental
      importance of the UPS in cardiac fibrosis has received much less attention. Our
      previous study found that proteasome inhibitor (MG132) treatment attenuated
      cardiac fibrosis and heart failure during the early and middle stages of pressure
      overload. However, the effects of this inhibitor on late-stage pressure overload
      hearts remain unclear and controversial. The present study was designed to
      investigate the effects and possible mechanisms of MG132 on cardiac fibrosis and
      dysfunction during the late stages of pressure overload. Male Sprague Dawley rats
      with abdominal aortic constriction (AAC) or a sham operation received an
      intraperitoneal injection of MG132 (0.1 mg kg-1 day-1) or vehicle for 16 weeks.
      Left ventricular (LV) function, collagen deposition and Ang II levels were
      evaluated at study termination. Ang II-stimulated adult rat cardiac fibroblasts
      were utilized to examine the effects of MG132 on collagen synthesis and the
      relationship between the renin-angiotensin-aldosterone system (RAAS) and the UPS.
      MG132 treatment attenuated ventricular dysfunction by suppressing cardiac
      fibrosis rather than inhibiting cardiac hypertrophy during the late-stages of
      pressure overload. We also found that Ang II activates UPS in the heart and MG132
      attenuates Ang II-induced collagen synthesis via suppression of the NF-kappaB/TGF
      beta/Smad2 signaling pathways. Proteasome inhibition therefore could provide a
      new promising therapeutic strategy to prevent cardiac fibrosis and progression of
      heart failure even during the late-stages of pressure overload.

PMID- 23142713
TI  - Magnetic drug targeting in a permeable microvessel.
AB  - A mathematical model is presented for predicting magnetic targeting of
      multifunctional carrier particles that deliver therapeutic agents to malignant
      tissue in vivo. These particles consist of a nonmagnetic core material that
      contains embedded magnetic nanoparticles and therapeutic agents such as
      photodynamic sensitizers. For in vivo therapy, the particles are injected into
      the microvascular system upstream from malignant tissue, and captured at the
      tumor using an applied magnetic field. In this paper, a mathematical model is
      developed for predicting non-invasive magnetic targeting of therapeutic carrier
      particles in a microvessel. The flow of blood in the microvessel is described by
      a two-phase Casson fluid model. The Darcy model is used to characterize the
      permeable nature of the inner wall of the microvessel. The fluidic force on the
      carrier traversing the microvessel and the magnetic force due to the external
      magnetic field is taken into account. We solved the system of coupled equations
      to obtain the capture condition for the carrier particle in the non-invasive
      case. The model enables rapid parametric analysis of magnetic targeting as a
      function of key variables including the size and shape of the carrier particle,
      the properties and volume fraction of the imbedded magnetic nanoparticles, the
      properties of the magnet, the microvessel and the permeability of the
      microvessel.

PMID- 23142714
TI  - Understanding coronary artery disease using twin studies.
AB  - Twins have fascinated human communities since the beginning of recorded history.
      In cardiovascular research, twin studies played a pivotal role in the discovery
      of the genetic basis of coronary artery disease, myocardial infarction and most
      of their associated risk factors. Matched for age, prenatal and postnatal
      environmental factors, discordant monozygous twin pairs provide a means to
      enhance the power to analyse epigenetic and metagenomic mechanisms. In the near
      future, combining the monozygous discordant twin study design with the recent
      advance of the sequencing technologies it will be possible to explore the
      complexity of the gene-environment relationships and individual variability to
      provide important insights into the pathogenesis of coronary artery
      disease/myocardial infarction.

PMID- 23142715
TI  - Effects of valence and arousal on written word recognition: time course and ERP
      correlates.
AB  - Models of affect assume a two-dimensional framework, composed of emotional
      valence and arousal. Although neuroimaging evidence supports a neuro-functional
      distinction of their effects during single word processing, electrophysiological
      studies have not yet compared the effects of arousal within the same category of
      valence (positive and negative). Here we investigate effects of arousal and
      valence on written lexical decision. Amplitude differences between emotion and
      neutral words were seen in the early posterior negativity (EPN), the late
      positive complex and in a sustained slow positivity. In addition, trends towards
      interactive effects of valence and arousal were observed in the EPN, showing
      larger amplitude for positive, high-arousal and negative, low-arousal words. The
      results provide initial evidence for interactions between arousal and valence
      during processing of positive words and highlight the importance of both
      variables in studies of emotional stimulus processing.

PMID- 23142716
TI  - Audiovisual integration in the primary auditory cortex of an awake rodent.
AB  - Much is known about the behavioral and physiological aspects of multimodal
      integration in primates, whereas less is known about the extent of audiovisual
      integration in other species. This study investigated the temporal integration of
      audiovisual stimuli in the primary auditory cortex (A1) of a standard animal
      model of auditory physiology: the Mongolian gerbil (Meriones unguiculatus). We
      recorded single unit responses to auditory and visual stimuli in the A1 of awake
      gerbils. A tone burst (auditory stimulus) paired with a flashing light (visual
      stimulus) at differing lag times (from 0 to +/-160ms) was presented contralateral
      to the recording site. As a result, the auditory response was altered
      significantly by the visual stimulus in more than 25% of the A1 units. The effect
      of the visual stimulus on the auditory response decreased as the time lag between
      the two modalities increased. The influence of the visual stimulus remained
      relatively greater when it preceded rather than followed the auditory stimulus.
      These results suggest that the A1 and earlier (subcortical) auditory structures
      of the rodent are capable of temporally integrating information from auditory and
      visual modalities.

PMID- 23142717
TI  - Anti-glutamate receptor E2 antibodies in psychiatric patients with anti-thyroid
      autoantibodies--a prevalence study in Japan.
AB  - Patients with anti-thyroid antibodies (ATAs) present various kinds of psychiatric
      conditions. When these psychiatric patients with ATAs (PPATs) show responsiveness
      to immunotherapy, they are frequently diagnosed with a diffuse progressive type
      of Hashimoto's encephalopathy (HE). Anti-glutamate receptor E2 subunit (GluRE2)
      antibodies have previously been reported in HE patients. However, it is unclear
      whether there is any relationship between PPATs, including HE patients, and anti
      GluRE2 antibodies. We investigated anti-GluRE2 antibodies in the serum and
      cerebrospinal fluid (CSF) of 15 PPATs, and we compared the results with those of
      11 patients with neuropsychiatric systemic lupus erythematosus (NPSLE), an anti
      glutamate receptor antibody-related disease. We then compared the
      neuropsychiatric symptoms between the PPATs with and without anti-GluRE2
      antibodies. The prevalence of anti-GluRE2 antibodies was significantly higher in
      the CSF than in the serum of PPATs (41.7% versus 6.7%; p=0.040). The prevalence
      of anti-GluRE2 antibodies was slightly higher in the CSF of PPATs than NPSLE
      patients. PPAT-GluR(+)s showed a significantly higher prevalence of emotional
      instability (100% versus 33.3%; p=0.03) and also showed a significantly lower
      prevalence of delusions (0% versus 100%; p=0.001) and hallucinations (17% versus
      83%; p=0.038) than PPAT-GluR(-)s. Our results suggest that anti-GluRE2 antibodies
      may be associated with the neuropsychiatric manifestation of PPATs.

PMID- 23142718
TI  - Organization of the neuroepithelial actin cytoskeleton is regulated by heparan
      sulfation during neurulation.
AB  - Heparan sulfate and cytoskeletal actin microfilaments have both been shown to be
      important regulators of neural tube closure during embryonic development. To
      determine the functional relationship of these two molecules in formation of the
      spinal neural tube, we cultured ARC mouse embryos at embryonic day E8.5 in the
      presence of chlorate, a competitive inhibitor of glycosaminoglycan sulfation, and
      examined the effects on organization of actin microfilaments in the
      neuroepithelium. Compared against embryos cultured under control conditions,
      chlorate-treated embryos had shortened posterior neuropore, a loss of median
      hinge point formation and increased bending at the paired dorsolateral hinge
      points. Furthermore, apical organization of actin microfilaments in the
      neuroepithelial cells was absent, and this was associated with convex bending of
      the neuroepithelium. The results suggest that heparan sulfate is an important
      determinant of cytoskeletal actin organization during spinal neurulation, and
      that its biological action is dependent on sulfation of the heparan molecule.

PMID- 23142719
TI  - Alpha-crystallin promotes rat olfactory ensheathing cells survival and
      proliferation through regulation of PI3K/Akt/mTOR signaling pathways.
AB  - Transplantation of cultured olfactory ensheathing cells (OECs) into lesions can
      promote axonal regeneration. However, the acutely injured CNS environment affects
      the survival and proliferation of OECs which might impair its therapy effects. To
      investigate whether alpha-crystallin can promote the survival and proliferation
      of OECs, OECs were cultured with alpha-crystallin. The survival of OECs was
      assessed by counting the numbers of p75-labeled OECs. Cellular proliferative
      activity was estimated by flow cytometry and quantification of BrdU-labeled
      cells. Phosphorylated p85, Akt and mammalian target of rapamycin (mTOR) were
      detected when OECs were culture for 7 days. Our results showed that the numbers
      of p75-labeled or Brdu-labeled OECs in alpha-crystallin group were much more than
      that in control group. And alpha-crystallin increased the phosphorylation of both
      p85, Akt and mTOR. LY294002 abrogated the ability of alpha-crystallin to
      phosphorylate Akt and mTOR, and decreased the percentage of cells in S and G2/M
      stage which were treated with alpha-crystallin. These findings indicated that
      alpha-crystallin positively regulated the activation of PI3K/Akt/mTOR signaling
      pathway and promote the proliferation and survival of cultured OECs.

PMID- 23142720
TI  - Memantine attenuates 3,4-methylenedioxymethamphetamine-induced hyperthermia in
      rats.
AB  - 3,4-Methylenedioxymethamphetamine (MDMA) is an illegal drug that can induce life
      threatening hyperthermia. No effective pharmacological treatment for MDMA-induced
      hyperthermia has yet been established. We investigated the effects of memantine,
      a non-competitive N-methyl-D-aspartate (NMDA)-type glutamate receptor antagonist
      and an alpha-7 nicotinic acetylcholine receptor (nAChR) antagonist, on MDMA
      induced hyperthermia in rats. Treatment of animals with memantine (10 or 20
      mg/kg) either before or after MDMA (10 mg/kg) administration significantly
      decreased the peak body temperature. Results from our microdialysis study
      indicated that pretreatment with memantine (20 mg/kg) before MDMA administration
      had no effect on the MDMA-induced increase in serotonin (5-HT) and dopamine (DA)
      levels in the anterior hypothalamus. MDMA-induced hyperthermia was significantly
      suppressed by pretreatment with the non-competitive NMDA receptor antagonist MK
      801 (0.5 mg/kg) and the competitive NMDA antagonist CGS 19755 (5 mg/kg), but not
      by the selective alpha-7 nAChR antagonist methyllycaconitine (6 or 10 mg/kg).
      These results indicate that the inhibitory effect of memantine on MDMA-induced
      hyperthermia may be due to its activity as an NMDA receptor antagonist and not as
      a result of a direct effect on the 5-HT or DA systems. The present study suggests
      that moderate doses of memantine may be useful for the treatment of MDMA-induced
      hyperthermia in humans.

PMID- 23142721
TI  - Electrical stimulation enhances neurogenin2 expression through beta-catenin
      signaling pathway of mouse bone marrow stromal cells and intensifies the effect
      of cell transplantation on brain injury.
AB  - Bone marrow stromal cells (BMSCs) have received significant attention for its use
      in neural regeneration. However, neural replacement by transplanted BMSCs was not
      very effective. Recently, the gene transfection method has improved the
      capability of cell transplantation; however, this method results in canceration
      and immune rejection. We induced the differentiation of mouse BMSCs into neural
      cells using electrical stimulation and transplanted the cells into traumatic
      brain injury (TBI) model mice. We found that the electrically stimulated cells
      have good potential to differentiate into neural cells and contribute to recovery
      from TBI without differentiating into astrocytes. In addition, we found that
      electrical stimulation enhanced neurogenin2 (Ngn2) expression. Ngn2 is involved
      in neural differentiation and inhibits astrocytic differentiation during cell
      growth. Furthermore, we found that this enhancement of Ngn2 expression occurred
      through beta-catenin signaling pathway. This study may contribute to the use of
      BMSCs for neural replacement in central nervous system diseases.

PMID- 23142722
TI  - Cryobiology of coral fragments.
AB  - Around the world, coral reefs are dying due to human influences, and saving
      habitat alone may not stop this destruction. This investigation focused on the
      biological processes that will provide the first steps in understanding the
      cryobiology of whole coral fragments. Coral fragments are a partnership of coral
      tissue and endosymbiotic algae, Symbiodinium sp., commonly called zooxanthellae.
      These data reflected their separate sensitivities to chilling and a
      cryoprotectant (dimethyl sulfoxide) for the coral Pocillopora damicornis, as
      measured by tissue loss and Pulse Amplitude Modulated fluorometry 3weeks post
      treatment. Five cryoprotectant treatments maintained the viability of the coral
      tissue and zooxanthellae at control values (1M dimethyl sulfoxide at 1.0, 1.5 and
      2.0h exposures, and 1.5M dimethyl sulfoxide at 1.0 and 1.5h exposures, P>0.05,
      ANOVA), whereas 2M concentrations did not (P<0.05, ANOVA). A seasonal response to
      chilling was observed in the coral tissue, but not in the zooxanthellae. During
      the winter when the fragments were chilled, the coral tissue remained relatively
      intact (~25% loss) post-treatment, but the zooxanthellae numbers in the tissue
      declined after 5min of chilling (P<0.05, ANOVA). However, in the late spring,
      coral tissue (~75% loss) and zooxanthellae numbers declined in response to
      chilling alone (P<0.05, ANOVA). When a cryoprotectant (1M dimethyl sulfoxide) was
      used in concert with chilling it protected the coral against tissue loss after
      45min of cryoprotectant exposure (P>0.05, ANOVA), but it did not protect against
      the loss of zooxanthellae (P<0.05, ANOVA). The zooxanthellae are the most
      sensitive element in the coral fragment complex and future cryopreservation
      protocols must be guided by their greater sensitivity.

PMID- 23142723
TI  - Penetration of verapamil across blood brain barrier following cerebral ischemia
      depending on both paracellular pathway and P-glycoprotein transportation.
AB  - BACKGROUND: Blood brain barrier (BBB) dysfunction is a common facet of cerebral
      ischemia, and the alteration of drug transporter, P-glycoprotein (P-gp), has been
      documented. AIMS: This study explores influence of damaged BBB and elevated P-gp
      on cerebral verapamil penetration after ischemia both in vivo and in vitro.
      METHODS: Middle cerebral artery occlusion (MCAO) induced ischemia/reperfusion
      (I/R) of rats, and Na(2)S(2)O(4) induced hypoxia/reoxygenation (H/R) damage of
      rat brain mirovessel endothelial cells (RBMECs) respectively, served as BBB
      breakdown model in vivo and in vitro. Evans-Blue (EB) extravagation and (125)I
      albumin were used to quantify BBB dysfunction; UPLC-MS/MS analytical method was
      performed to determine accurately the concentration of verapamil in brain tissue
      and cell. Flow cytometry, immunohistochemistry and western blotting were applied
      to evaluate transport function and protein expression of P-gp. RESULTS:
      Overexpressed ICAM-1 and MMP-9 mediated BBB dysfunction after ischemia, which
      induced EB leakage and (125)I-albumin uptake increase. Enhanced accumulation of
      verapamil in brain tissue, but intracellular concentration reduced evidently
      after H/R injury. Transcellular transportation of verapamil elevated when P-gp
      function or expression was inhibited after H/R injury. CONCLUSION: These data
      indicated that BBB penetration of verapamil under ischemia condition was not only
      depending on BBB breakdown, but also regulated by P-gp.

PMID- 23142724
TI  - Tenascin-C levels in synovial fluid are elevated after injury to the human and
      canine joint and correlate with markers of inflammation and matrix degradation.
AB  - OBJECTIVE: We have previously shown the capacity of tenascin-C (TN-C) to induce
      inflammatory mediators and matrix degradation in vitro in human articular
      cartilage. The objective of the present study was to follow TN-C release into
      knee synovial fluid after acute joint injury or in joint disease, and to
      correlate TN-C levels with markers of cartilage matrix degradation and
      inflammation. METHOD: Human knee synovial fluid samples (n = 164) were from a
      cross-sectional convenience cohort. Diagnostic groups were knee healthy
      reference, knee anterior cruciate ligament rupture, with or without concomitant
      meniscus lesions, isolated knee meniscus injury, acute inflammatory arthritis
      (AIA) and knee osteoarthritis (OA). TN-C was measured in synovial fluid samples
      using an enzyme-linked immunosorbent assay (ELISA) and results correlated to
      other cartilage markers. TN-C release was also monitored in joints of dogs that
      underwent knee instability surgery. RESULTS: Statistically significantly higher
      levels of TN-C compared to reference subjects were observed in the joint fluid of
      all human disease groups and in the dogs that underwent knee instability surgery.
      Statistically significant correlations were observed between the TN-C levels in
      the synovial fluid of the human patients and the levels of aggrecanase-dependent
      Ala-Arg-Gly-aggrecan (ARG-aggrecan) fragments and matrix metalloproteinases 1 and
      3. CONCLUSIONS: We find highly elevated levels of TN-C in human knee joints after
      injury, AIA or OA that correlated with markers of cartilage degradation and
      inflammation. TN-C in synovial fluid may serve dual roles as a marker of joint
      damage and a stimulant of further joint degradation.

PMID- 23142725
TI  - Alterations to the subchondral bone architecture during osteoarthritis: bone
      adaptation vs endochondral bone formation.
AB  - OBJECTIVE: Osteoarthritis (OA) is characterized by loss of cartilage and
      alterations in subchondral bone architecture. Changes in cartilage and bone
      tissue occur simultaneously and are spatially correlated, indicating that they
      are probably related. We investigated two hypotheses regarding this relationship.
      According to the first hypothesis, both wear and tear changes in cartilage, and
      remodeling changes in bone are a result of abnormal loading conditions. According
      to the second hypothesis, loss of cartilage and changes in bone architecture
      result from endochondral ossification. DESIGN: With an established bone
      adaptation model, we simulated adaptation to high load and endochondral
      ossification, and investigated whether alterations in bone architecture between
      these conditions were different. In addition, we analyzed bone structure
      differences between human bone samples with increasing degrees of OA, and
      compared these data to the simulation results. RESULTS: The simulation of
      endochondral ossification led to a more refined structure, with a higher number
      of trabeculae in agreement with the finding of a higher trabecular number in
      osteochondral plugs with severe OA. Furthermore, endochondral ossification could
      explain the presence of a "double subchondral plate" which we found in some human
      bone samples. However, endochondral ossification could not explain the increase
      in bone volume fraction that we observed, whereas adaptation to high loading
      could. CONCLUSION: Based on the simulation and experimental data, we postulate
      that both endochondral ossification and adaptation to high load may contribute to
      OA bone structural changes, while both wear and tear and the replacement of
      mineralized cartilage with bone tissue may contribute cartilage thinning.

PMID- 23142726
TI  - Role of chymotrypsin-like serine proteinase in white spot syndrome virus
      infection in Fenneropenaeus chinensis.
AB  - White spot syndrome virus (WSSV) caused a great economic loss in shrimp
      aquaculture. Although great efforts have been undertaken to characterize the
      virus disease during the last two decades, there are still lack of effective
      methods to prevent or cure it. In this study, we investigated the transcriptional
      expression profiles of 18 key immune-related genes in the Chinese shrimp
      Fenneropenaeus chinensis which was severely infected by WSSV. We found that the
      expression levels of 6 genes including chymotrypsin-like serine proteinase (CH
      SPase), heat shock protein 70 cognate (HSP70), penaeidin (PEN), peroxinectin
      (PO), proliferating cell nuclear antigen (PCNA) and argonaute (AGO) changed
      significantly, while the expression of the other 12 genes had no significant
      changes compared to the control group. Among the 6 screened genes, CH-SPase
      showed significantly up-regulation, while the other 5 ones were significantly
      down-regulated. Knockdown of the expression of CH-SPase in WSSV-infected Chinese
      shrimp reduced the copy number of WSSV and delayed cumulative mortalities,
      suggesting that CH-SPase is important for WSSV infection. This study will be
      helpful to control the disease in shrimp caused by WSSV.

PMID- 23142727
TI  - Biodegradable microparticles covalently linked to surface antigens of the
      scuticociliate parasite P. dicentrarchi promote innate immune responses in vitro.
AB  - The histiophagous scuticociliate endoparasite Philasterides dicentrarchi is an
      emerging pathogen that infects the turbot Scophthalmus maximus and thus causes
      important economic losses in turbot aquaculture. This in vitro study investigated
      the adjuvant capacity of biodegradable microspheres (MS) composed of two polymers
      (chitosan and Gantrez((r))) covalently coupled to surface antigens (Ag) of P.
      dicentrarchi. The coupled MS-Ag significantly stimulated the phagocytic response
      of both murine macrophages (RAW 264.7 cells) and leukocytes from the anterior
      kidney of turbot (HLK), at a level similar to that induced by zymosan A. The MS
      Ag also significantly increased production of reactive oxygen and nitrogen
      species, as shown by the increased O(2) consumption and stimulation of the
      respiratory burst and nitric oxide production by murine and in particular by
      turbot HLK. The MS-Ag stimulated the production of the proinflammatory cytokine
      tumour necrosis factor alpha (TNFalpha) by murine and turbot HLK. The results
      confirm the high adjuvant capacity of biodegradable MS covalently bound to Ag as
      regards stimulating the innate immune response, and they justify the use of MS in
      the production of safe and effective vaccines against fish pathogens.

PMID- 23142728
TI  - Identifiability of diffusion and sorption parameters from in situ diffusion
      experiments by using simultaneously tracer dilution and claystone data.
AB  - In situ diffusion experiments are performed in geological formations at
      underground research laboratories to overcome the limitations of laboratory
      diffusion experiments and investigate scale effects. Tracer concentrations are
      monitored at the injection interval during the experiment (dilution data) and
      measured from host rock samples around the injection interval at the end of the
      experiment (overcoring data). Diffusion and sorption parameters are derived from
      the inverse numerical modeling of the measured tracer data. The identifiability
      and the uncertainties of tritium and (22)Na(+) diffusion and sorption parameters
      are studied here by synthetic experiments having the same characteristics as the
      in situ diffusion and retention (DR) experiment performed on Opalinus Clay.
      Contrary to previous identifiability analyses of in situ diffusion experiments,
      which used either dilution or overcoring data at approximate locations, our
      analysis of the parameter identifiability relies simultaneously on dilution and
      overcoring data, accounts for the actual position of the overcoring samples in
      the claystone, uses realistic values of the standard deviation of the measurement
      errors, relies on model identification criteria to select the most appropriate
      hypothesis about the existence of a borehole disturbed zone and addresses the
      effect of errors in the location of the sampling profiles. The simultaneous use
      of dilution and overcoring data provides accurate parameter estimates in the
      presence of measurement errors, allows the identification of the right hypothesis
      about the borehole disturbed zone and diminishes other model uncertainties such
      as those caused by errors in the volume of the circulation system and the
      effective diffusion coefficient of the filter. The proper interpretation of the
      experiment requires the right hypothesis about the borehole disturbed zone. A
      wrong assumption leads to large estimation errors. The use of model
      identification criteria helps in the selection of the best model. Small errors in
      the depth of the overcoring samples lead to large parameter estimation errors.
      Therefore, attention should be paid to minimize the errors in positioning the
      depth of the samples. The results of the identifiability analysis do not depend
      on the particular realization of random numbers.

PMID- 23142729
TI  - A novel tylophorine analog W-8 up-regulates forkhead boxP3 expression and
      ameliorates murine colitis.
AB  - Tylophorine and analogs are phenanthroindolizidine alkaloids, several of which
      have been reported to have anticancer, antiviral, and anti-inflammatory
      properties. However, their function in the immune system remains widely unknown.
      Transcription factor Foxp3 is critical for the development and function of Treg,
      which down-regulates the immune system and maintains tolerance to self-antigens.
      In the present study, we defined a novel tylophorine analog, W-8, enhanced TGF
      beta-induced Foxp3 expression at the mRNA and the protein levels. Interestingly,
      W-8 synergistically increased the level of TGF-beta-induced p-Smad3 through
      inhibition of the AKT/mTOR pathway and enhanced the demethylation of the promoter
      region of the Foxp3 through inhibition of the ERK pathway and DNMT1 expression.
      Moreover, administration of W-8 suppressed TNBS-induced murine colitis and
      increased Tregs in lymphoid tissues. Finally, W-8 enhanced conversion of naive T
      cells to Tregs in vivo. In summary, our results defined a novel compound that
      enhanced Foxp3 expression through transcriptional and epigenetic programs, and it
      might serve as a therapeutic agent for inflammatory diseases.

PMID- 23142730
TI  - P-cadherin controls the differentiation of oral keratinocytes by regulating
      cytokeratin 1/10 expression via C/EBP-beta-mediated signaling.
AB  - P-cadherin belongs to the family of Ca(2+)-dependent homophilic glycosylated cell
      adhesion molecules. In the normal oral epithelium it shows a strong expression in
      the basal cell layer which gradually decreases in the suprabasal cell layers. The
      exact role of P-cadherin during the development and homeostasis of the oral
      epithelium has not been elucidated, yet. Here, we show for the first time that P
      cadherin controls differentiation by regulating cytokeratin (CK) 1/10 expression
      in primary oral keratinocytes (POK) from normal, but interestingly not in POKs
      from oral squamous cell carcinoma (OSCC) tissue. SiRNA knockdown of P-cadherin in
      normal POKs revealed a strong upregulation of CK1/10 expression on mRNA and
      protein level. In contrast, E-cadherin knockdown in normal oral keratinocytes did
      not show any influence on CK1/10 expression. Moreover, in comparison with normal
      control keratinocytes normal oral keratinocytes with reduced P-cadherin
      expression displayed an enhanced expression and a stronger nuclear staining of
      C/EBP-beta, a well-known regulator of CK1/10 expression in keratinocytes.
      Furthermore, after P-cadherin knockdown in normal POKs the promoter activity of a
      C/EBP-responsive luciferase construct was significantly higher than in normal
      POKs with regular P-cadherin expression. Additionally, we noticed a proliferation
      advantage in normal oral keratinocytes in contrast to keratinocytes with
      diminished P-cadherin expression. However, the inverted effect was seen in tumor
      derived primary oral keratinocytes. In summary, we show that P-cadherin
      contributes to the keratinocyte differentiation in the oral epithelium by
      influencing the CK1 and CK10 expression via C/EBP-beta-mediated signaling in
      normal but not in tumor derived oral keratinocytes from OSCC patients.

PMID- 23142731
TI  - Use of poly(DL-lactide-epsilon-caprolactone) membranes and mesenchymal stem cells
      from the Wharton's jelly of the umbilical cord for promoting nerve regeneration
      in axonotmesis: in vitro and in vivo analysis.
AB  - Cellular systems implanted into an injured nerve may produce growth factors or
      extracellular matrix molecules, modulate the inflammatory process and eventually
      improve nerve regeneration. In the present study, we evaluated the therapeutic
      value of human umbilical cord matrix MSCs (HMSCs) on rat sciatic nerve after
      axonotmesis injury associated to Vivosorb(r) membrane. During HMSCs expansion and
      differentiation in neuroglial-like cells, the culture medium was collected at 48,
      72 and 96 h for nuclear magnetic resonance (NMR) analysis in order to evaluate
      the metabolic profile. To correlate the HMSCs ability to differentiate and
      survival capacity in the presence of the Vivosorb(r) membrane, the [Ca(2+)]i of
      undifferentiated HMSCs or neuroglial-differentiated HMSCs was determined by the
      epifluorescence technique using the Fura-2AM probe. The Vivosorb(r) membrane
      proved to be adequate and used as scaffold associated with undifferentiated HMSCs
      or neuroglial-differentiated HMSCs. In vivo testing was carried out in adult rats
      where a sciatic nerve axonotmesis injury was treated with undifferentiated HMSCs
      or neuroglial differentiated HMSCs with or without the Vivosorb(r) membrane.
      Motor and sensory functional recovery was evaluated throughout a healing period
      of 12 weeks using sciatic functional index (SFI), extensor postural thrust (EPT),
      and withdrawal reflex latency (WRL). Stereological analysis was carried out on
      regenerated nerve fibers. In vitro investigation showed the formation of typical
      neuroglial cells after differentiation, which were positively stained for the
      typical specific neuroglial markers such as the GFAP, the GAP-43 and NeuN. NMR
      showed clear evidence that HMSCs expansion is glycolysis-dependent but their
      differentiation requires the switch of the metabolic profile to oxidative
      metabolism. In vivo studies showed enhanced recovery of motor and sensory
      function in animals treated with transplanted undifferentiated and differentiated
      HMSCs that was accompanied by an increase in myelin sheath. Taken together, HMSC
      from the umbilical cord Wharton jelly might be useful for improving the clinical
      outcome after peripheral nerve lesion.

PMID- 23142732
TI  - Rigid matrix supports osteogenic differentiation of stem cells from human
      exfoliated deciduous teeth (SHED).
AB  - Stem cell fate can be induced by the grade of stiffness of the extracellular
      matrix, depending on the developed tissue or complex tissues. For example, a
      rigid extracellular matrix induces the osteogenic differentiation in bone marrow
      derived mesenchymal stem cells (MSCs), while a softer surface induces the
      osteogenic differentiation in dental follicle cells (DFCs). To determine whether
      differentiation of ectomesenchymal dental precursor cells is supported by similar
      grades of extracellular matrices (ECMs) stiffness, we examined the influence of
      the surface stiffness on the proliferation and osteogenic differentiation of stem
      cells from human exfoliated deciduous teeth (SHED). Cell proliferation of SHED
      was significantly decreased on cell culture surfaces with a muscle-like
      stiffness. A dexamethasone-based differentiation medium induced the osteogenic
      differentiation of SHED on substrates of varying mechanical stiffness. Here, the
      hardest surface improved the induction of osteogenic differentiation in
      comparison to that with the softest stiffness. In conclusion, our study showed
      that the osteogenic differentiation of ectomesenchymal dental precursor cells
      SHED and DFCs are not supported by similar grades of ECM stiffness.

PMID- 23142733
TI  - Semaphorin 3A controls timing and patterning of the dental pulp innervation.
AB  - Timing and patterning of dental pulp innervation are strictly spatio-temporally
      regulated but it is still not known how they are controlled at molecular level.
      We analyzed postnatal innervation of the dental pulp in the mandibular first
      molar of mice deficient for Semaphorin 3A (Sema3A) axon repellant molecule.
      Immunohistochemical localization of nerve fibers on serial sections covering the
      whole tooth germs using anti-peripherin antibody revealed that nerve fibers were
      prematurely present within the preodontoblast layer next to the inner enamel
      epithelium already at PN0 in Sema3A(-/-) mice. In contrast, in the wild-type
      (Sema3A(+/+)) mice nerve fibers were seen in the pulp only after enamel formation
      at PN3. The nerves in Sema3A(-/-) pulp were notably defasciculated and thinner
      compared to that of Sema3A(+/+) mice. A premature formation of an abnormal,
      enlarged nerve plexus with a high number of arborizations was apparent in the
      pulp-dentin border target area in Sema3A(-/-) already at PN2 whereas in the wild
      type mice the first sign of plexus formation was seen at PN7. The expression of
      mRNAs for Ngf, Gdnf and Ncam neuroregulatory molecules in mandibular molar as
      well as receptors for neurotrophic factors and class 3 semaphorins including
      Sema3A (TrkA, p75, TrkB, TrkC, Ret, Npn1, Npn2, PlxA4) in trigeminal ganglia were
      not altered in the Sema3A(-/-) mice. Collectively, this data show that Sema3A
      serves an essential role in molar tooth pulp innervation controlling the timing
      of nerve fiber penetration into the pulp, their patterning and the formation of
      nerve plexus at pulp-dentin border area, and provide further support for the
      hypothesis that tooth innervation is regulated by the coordinated activity of
      locally expressed neuroregulatory molecules exerting positive and negative
      influences on growing dental nerve fibers.

PMID- 23142734
TI  - Paraxial left-sided nodal expression and the start of left-right patterning in
      the early chick embryo.
AB  - A common element during early left-right patterning of the vertebrate body is
      left-sided nodal expression in the early-somite stage lateral plate mesoderm.
      Leftward cell movements near the node of the gastrulating chick embryo recently
      offered a plausible mechanism for breaking the presomite-stage molecular symmetry
      in those vertebrates which lack rotating cilia on the notochord or equivalent
      tissues. However, the temporal and functional relationships between generation of
      the known morphological node asymmetry, onset of leftward cell movements and
      establishment of stable molecular asymmetry in the chick remain unresolved. This
      study uses high-resolution light microscopy and in situ gene expression analysis
      to show that intranodal cell rearrangement during the phase of counter-clockwise
      node torsion at stage 4+ is immediately followed by symmetry loss and
      rearrangement of shh and fgf8 expression in node epiblast between stages 5- and
      5+. Surprisingly, left-sided nodal expression starts at stage 5-, too, but lies
      in the paraxial mesoderm next to the forming notochordal plate, and can be
      rendered symmetrical by minimal mechanical disturbance of distant tissue
      integrity at stage 4. The "premature" paraxial nodal expression together with
      morphological and molecular asymmetries in, and near, midline compartments
      occurring at defined substages of early gastrulation help to identify a new
      narrow time window for early steps in left-right patterning in the chick and
      support the concept of a causal relationship between a-still enigmatic-chiral
      (motor) protein, cell movements and incipient left-right asymmetry in the amniote
      embryo.

PMID- 23142735
TI  - Epidemiologic and clinical characteristics of 458 Tunisian patients with
      intellectual deficiency and a reconsidered diagnostic strategy.
AB  - Intellectual Deficiency (ID) is a common neuropsychiatric disorder whose
      etiopathogenesis still insufficiently understood. In the last decade, several
      surveys, assessing epidemiologic, clinical and etiologic parameters of ID, have
      been performed but none of them is realized in a Tunisian population. In this
      retrospective survey, we propose to study these parameters, in a Tunisian cohort
      of 458 patients with constitutional ID, and to assess our diagnostic strategy.
      Data analyses, by the SPSS program, reveal a male predominance, a high level of
      consanguinity, an advanced mean age of patients, a rare frequentation of
      specialized institutions by the severely affected patients, and a high frequency
      of familial forms with predominance of the recessive autosomal ones. The study of
      clinical parameters and investigations' results shows that 72.1% of our patients
      present a syndromic ID. For these patients, chromosomal anomalies are rarely
      described, EEG anomalies were usually non-specific in patients without clinical
      evidence of epilepsy, and brain anomalies are common in patients with severe ID,
      neurological symptoms or history of seizures. Aetiology is identified in 13.1% of
      them whereas it is still unknown in 100% of patients with non-specific ID. This
      study allows us to better characterize, epidemiologically and clinically, the
      first large Tunisian cohort of patients with ID and to assess our diagnostic
      strategy in order to propose a revised one that will improve the diagnostic lead,
      the care chain and the preventive resources of ID.

PMID- 23142736
TI  - Mutations in Bacchus reveal a tyramine-dependent nuclear regulator for acute
      ethanol sensitivity in Drosophila.
AB  - Fruit flies and humans display remarkably similar behavioral responses to ethanol
      intoxication. Here we report that loss-of-function mutations in the CG9894 gene
      (now named Bacchus or Bacc) attenuate ethanol sensitivity in flies. Bacc encodes
      a broadly expressed nuclear protein with a motif similar to ribosomal RNA-binding
      domains. The ethanol-related activity of Bacc was mapped to Tdc2-GAL4 neurons.
      Genetic and pharmacological analyses suggest that ethanol resistance of Bacc
      mutants is caused by increased tyramine beta-hydroxylase (tbetah) activity that
      results in excessive conversion of tyramine (TA) to octopmaine (OA). Thus, tbetah
      and its negative regulator Bacc define a novel biogenic amine-mediated signaling
      pathway that regulates fly ethanol sensitivity. Importantly, elevated tbh
      activity has been shown to promote fighting behavior, raising the possibility
      that the Bacc/tbh pathway may regulate complex traits in addition to acute
      ethanol response.

PMID- 23142737
TI  - Protective effects of erythropoietin on astrocytic swelling after oxygen-glucose
      deprivation and reoxygenation: mediation through AQP4 expression and MAPK
      pathway.
AB  - Recent in vivo studies have shown that erythropoietin (EPO) offers strong
      protection against brain edema. However, the intracellular and molecular
      mechanisms behind this beneficial effect have not been specified. The aim of this
      study was to determine whether human erythropoietin (rhEPO) reduces the
      astrocytic swelling created by oxygen-glucose deprivation followed by
      reoxygenation (OGD/Reox) in vitro and whether this effect can be mediated through
      the modulation of aquaporin4 (AQP4) expression in the plasma membrane (PM) and
      phosphorylation of the mitogen-activated protein kinase pathway (MAPK) pathway.
      Our results showed that OGD/Reox produced increase in cell volume, morphological
      swelling, and mitochondrial swelling. These changes were associated with the up
      regulation of AQP4 in PM and the over-activation of MAPK. Silencing AQP4
      expression using small interfering ribonucleic acid for AQP4 was found to block
      astrocytic swelling. Inhibition of the over-activation of MAPK mitigated the PM
      AQP4 overabundance and cellular swelling. As expected, treatment with rhEPO
      significantly reduced the OGD/Reox-induced increase in cell volume, morphological
      swelling, and mitochondrial swelling as well as the up-regulation of AQP4 in PM.
      In addition, cultures treated with the neutralizing anti-EPO antibody worsened
      the PM AQP4 abundance and cellular swelling, abolishing the protective effects
      mediated by rhEPO treatment. Furthermore, the over-activation of these MAPK after
      OGD/Reox was attenuated by rhEPO treatment significantly. In conclusion, our data
      strongly suggest that rhEPO can protect astrocytes from swelling caused by
      ischemia and reperfusion-like injury. This neuroprotective capacity is partially
      mediated by diminishing the MAPK-activity-dependent overabundance of AQP4 in PM.

PMID- 23142738
TI  - Interpretation of atom probe tomography data for the intermetallic TiAl+Nb by
      means of field evaporation simulation.
AB  - In this paper simulations of the field evaporation process during field ion
      microscopy (FIM) and atom probe tomography (APT) are presented and compared with
      experimental data. The Muller-Schottky-model was extended to include the local
      atomic arrangement on the evaporation process of atoms. This arrangement was
      described by the sum of the next-neighbor-binding-energies, which differ for an
      atom of type A, depending on how many A-A, B-B or A-B bonds are present. Thus
      simulations of APT-data of intermetallic phases become feasible. In this study
      simulations of L1(0)-TiAl with additions of Nb are compared with experimental
      data. Certain artifacts, which appear for experimental data are treated as well.

PMID- 23142739
TI  - One-dimensional autocorrelation and power spectrum density functions of irregular
      regions.
AB  - Scanning probe microscopy (SPM) can be effectively used for evaluation of
      nanoscale roughness of surfaces obtained by different technological processes.
      Spectral properties of surface roughness can be evaluated using algorithms based
      on Fast Fourier Transform (FFT). For data that are not rectangular, this
      approach, however fails. In this paper we describe a modification of SPM data
      evaluation algorithms enabling to use FFT based approach even for irregular and
      non-continuous data. This opens novel possibilities in analysis of local surface
      roughness in many fields, e.g. on nanoparticles, semiconductor structures or any
      other nanostructured samples prepared using nanotechnology methods. Together with
      theoretical description of proposed method we present benchmarks for its
      performance and typical results of its application on different samples.

PMID- 23142740
TI  - Extraction of topographic and material contrasts on surfaces from SEM images
      obtained by energy filtering detection with low-energy primary electrons.
AB  - Secondary electron microscope (SEM) images have been obtained for practical
      materials using low primary electron energies and an in-lens type annular
      detector with changing negative bias voltage supplied to a grid placed in front
      of the detector. The kinetic-energy distribution of the detected electrons was
      evaluated by the gradient of the bias-energy dependence of the brightness of the
      images. This is divided into mainly two parts at about 500 V, high and low
      brightness in the low- and high-energy regions, respectively and shows difference
      among the surface regions having different composition and topography. The
      combination of the negative grid bias and the pixel-by-pixel image subtraction
      provides the band-pass filtered images and extracts the material and topographic
      information of the specimen surfaces.

PMID- 23142741
TI  - Reflection-based near-field ellipsometry for thin film characterization.
AB  - This paper presents a near-field ellipsometry method for nano-scale thin film
      characterization. The method is based on a reflection configuration of near-field
      optical detection. In the method, a new set of ellipsometry equations is
      established by taking into consideration the near-field sample-probe interaction
      and the topography of the thin film. Experimental and simulation results have
      shown that the proposed near-field ellipsometry is able to attain precise thin
      film characterization with nano-scale lateral resolution.

PMID- 23142742
TI  - Image formation mechanisms in scanning electron microscopy of carbon nanotubes,
      and retrieval of their intrinsic dimensions.
AB  - We present a detailed analysis of the image formation mechanisms that are
      involved in the imaging of carbon nanotubes with scanning electron microscopy
      (SEM). We show how SEM images can be modelled by accounting for surface
      enhancement effects together with the absorption coefficient for secondary
      electrons, and the electron-probe shape. Images can then be deconvoluted,
      enabling retrieval of the intrinsic nanotube dimensions. Accurate estimates of
      their dimensions can thereby be obtained even for structures that are comparable
      to the electron-probe size (on the order of 2 nm). We also present a simple and
      robust model for obtaining the outer diameter of nanotubes without any detailed
      knowledge about the electron-probe shape.

PMID- 23142743
TI  - The influence of spatial and temporal averaging on interpretation of HRTEM images
      of solid-liquid interfaces.
AB  - The effects of spatial and temporal averaging on high-resolution transmission
      electron microscope (HRTEM) images and associated intensity profiles of a solid
      liquid Al interface were investigated using atomic coordinates obtained from
      molecular dynamics simulations. It was found that intensity profiles obtained by
      spatial averaging across the solid-liquid interface capture the variation in
      structural features nearly as well as time-averaged intensity profiles. This
      suggests that adequate spatial averaging of a single HRTEM image can be used to
      study the contrast from interfaces, and thereby, the structural details, without
      the need for more time-consuming, computer-intensive time averaged analyses. The
      limitations of this method are also discussed.

PMID- 23142744
TI  - Influence of total beam current on HRTEM image resolution in differentially
      pumped ETEM with nitrogen gas.
AB  - Environmental transmission electron microscopy (ETEM) enables the study of
      catalytic and other reaction processes as they occur with Angstrom-level
      resolution. The microscope used is a dedicated ETEM (Titan ETEM, FEI Company)
      with a differential pumping vacuum system and apertures, allowing aberration
      corrected high-resolution transmission electron microscopy (HRTEM) imaging to be
      performed with gas pressures up to 20 mbar in the sample area and with
      significant advantages over membrane-type E-cell holders. The effect on image
      resolution of varying the nitrogen gas pressure, electron beam current density
      and total beam current were measured using information limit (Young's fringes) on
      a standard cross grating sample and from silicon crystal lattice imaging. As
      expected, increasing gas pressure causes a decrease in HRTEM image resolution.
      However, the total electron beam current also causes big changes in the image
      resolution (lower beam current giving better resolution), whereas varying the
      beam current density has almost no effect on resolution, a result that has not
      been reported previously. This behavior is seen even with zero-loss filtered
      imaging, which we believe shows that the drop in resolution is caused by elastic
      scattering at gas ions created by the incident electron beam. Suitable conditions
      for acquiring high resolution images in a gas environment are discussed. Lattice
      images at nitrogen pressures up to 16 mbar are shown, with 0.12 nm information
      transfer at 4 mbar.

PMID- 23142745
TI  - Detector non-uniformity in scanning transmission electron microscopy.
AB  - A non-uniform response across scanning transmission electron microscope annular
      detectors has been found experimentally, but is seldom incorporated into
      simulations. Through case study simulations, we establish the nature and scale of
      the discrepancies which may arise from failing to account for detector non
      uniformity. If standard detectors are used at long camera lengths such that the
      detector is within or near to the bright field region, we find errors in contrast
      of the order of 10%, sufficiently small for qualitative work but non-trivial as
      experiments become more quantitative. In cases where the detector has been
      characterized in advance, we discuss the detector response normalization and how
      it may be incorporated in simulations.

PMID- 23142746
TI  - Rapid measurement of nanoparticle thickness profiles.
AB  - A method to measure the thickness of a single-crystal nanoparticle in the
      direction parallel to the incident beam from annular dark field scanning
      transmission electron microscope (ADF-STEM) images is reported, providing a map
      of thickness versus position across the nanoparticle--a 'thickness profile'
      image. The method is rapid and hence suitable for surveying large numbers of
      nanoparticles. The method measures the intensity scattered to a characterised ADF
      detector and compares this to the incident beam intensity, to obtain a normalized
      ADF image. The normalised intensity is then converted to thickness via dynamical
      ADF image simulations. The method is accurate within 10% and the precision is
      dominated primarily by 'shot noise'. Merits and limitations of this method are
      discussed. A method to calibrate the response function of the ADF detector
      without external equipment is also described, which is applicable to the entire
      range of gain and background settings.

PMID- 23142747
TI  - Symmetry quantification and mapping using convergent beam electron diffraction.
AB  - We propose a new algorithm to quantify symmetry recorded in convergent beam
      electron diffraction (CBED) patterns and use it for symmetry mapping in materials
      applications. We evaluate the effectiveness of the profile R-factor (R(p)) and
      the normalized cross-correlation coefficient (gamma) for quantifying the amount
      of symmetry in a CBED pattern. The symmetry quantification procedures are
      automated and the algorithm is implemented as a DM (Digital Micrograph((c)))
      script. Experimental and simulated CBED patterns recorded from a Si single
      crystal are used to calibrate the proposed algorithm for the symmetry
      quantification. The proposed algorithm is then applied to a Si sample with
      defects to test the sensitivity of symmetry quantification to defects. Using the
      mirror symmetry as an example, we demonstrate that the normalized cross
      correlation coefficient provides an effective and robust measurement of the
      symmetry recorded in experimental CBED patterns.

PMID- 23142748
TI  - Optimum aberration coefficients for recording high-resolution off-axis holograms
      in a Cs-corrected TEM.
AB  - Amongst the impressive improvements in high-resolution electron microscopy, the
      Cs-corrector also has significantly enhanced the capabilities of off-axis
      electron holography. Recently, it has been shown that the signal above noise in
      the reconstructable phase can be significantly improved by combining holography
      and hardware aberration correction. Additionally, with a spherical aberration
      close to zero, the traditional optimum focus for recording high-resolution
      holograms ("Lichte's defocus") has become less stringent and both, defocus and
      spherical aberration, can be selected freely within a certain range. This new
      degree of freedom can be used to improve the signal resolution in the
      holographically reconstructed object wave locally, e.g. at the atomic positions.
      A brute force simulation study for an aberration corrected 200 kV TEM is
      performed to determine optimum values for defocus and spherical aberration for
      best possible signal to noise in the reconstructed atomic phase signals. Compared
      to the optimum aberrations for conventional phase contrast imaging (NCSI), which
      produce "bright atoms" in the image intensity, the resulting optimum values of
      defocus and spherical aberration for off-axis holography enable "black atom
      contrast" in the hologram. However, they can significantly enhance the local
      signal resolution at the atomic positions. At the same time, the benefits of
      hardware aberration correction for high-resolution off-axis holography are
      preserved. It turns out that the optimum is depending on the object and its
      thickness and therefore not universal.

PMID- 23142749
TI  - Simulation of the backscattered electron intensity of multi layer structure for
      the explanation of secondary electron contrast.
AB  - The intensities of the secondary electrons (SE) and of the backscattered
      electrons (BSE) at energy 100 eV have been measured on a Ni/C/Ni/C/Ni/C/(Si
      substrate) multilayer structure by exciting it with primary electrons of 5, 2.5
      and 1.25 keV energies. It has been found that both intensities similarly vary
      while thinning the specimen. The difference as small as 4 nm in the underlying
      layer thicknesses resulted in visible intensity change. Utilizing this intensity
      change, the thickness difference of neighboring regions could be revealed from
      the SE image. No simple phenomenological model was found to interpret the change
      of intensity, thus the intensity of the BSE electrons has been calculated by
      means of a newly developed Monte Carlo simulation. This code also considers the
      secondary electron generation and transport through the solid. The calculated and
      measured intensities agree well supporting the validity of the model.

PMID- 23142750
TI  - Full tip imaging in atom probe tomography.
AB  - Atom probe tomography (APT) is capable of simultaneously revealing the chemical
      identities and three dimensional positions of individual atoms within a needle
      shaped specimen, but suffers from a limited field-of-view (FOV), i.e., only the
      core of the specimen is effectively detected. Therefore, the capacity to analyze
      the full tip is crucial and much desired in cases that the shell of the specimen
      is also the region of interest. In this paper, we demonstrate that, in the
      analysis of III-V nanowires epitaxially grown from a substrate, the presence of
      the flat substrate positioned only micrometers away from the analyzed tip apex
      alters the field distribution and ion trajectories, which provides extra image
      compression that allows for the analysis of the entire specimen. An array of
      experimental results, including field desorption maps, elemental distributions,
      and crystallographic features clearly demonstrate the fact that the whole tip has
      been imaged, which is confirmed by electrostatic simulations.

PMID- 23142751
TI  - Improving the scanning speed of atomic force microscopy at the scanning range of
      several tens of micrometers.
AB  - The atomic force microscope (AFM) is a powerful instrument which can measure the
      surface of samples at the nanoscale. The resonance of the scanner in xy
      directions, and the feedback control in the z direction are two major sources of
      image distortion at high scan speed. In order to improve the scanning speed of
      the AFM, a low-cost and easy method, which includes sinusoidal scans in the fast
      scan direction, and an intelligent fuzzy controller in the z direction, is
      proposed in this paper. The use of a single-frequency driving signal in the fast
      scan direction allows the scanner to move at a higher speed without exciting its
      mechanical resonance. The intelligent fuzzy controller automatically selects
      appropriate PI parameters through the analysis of the tracking errors, thus
      improving the dynamic tracking performance of the z scanner. The development and
      functioning of the sinusoidal fast scans and the intelligent fuzzy controller are
      demonstrated, as well as how this approach significantly achieves faster scans
      and a higher resolution AFM imaging.

PMID- 23142752
TI  - Imaging of three-dimensional (Si,Ge) nanostructures by off-axis electron
      holography.
AB  - Quantitative phase mapping in transmission electron microscopy is applied to
      image the three-dimensional (3D) morphology of (Si,Ge) islands grown on Si
      substrates. The phase shift of the transmitted electrons induced by the crystal
      inner potential was recorded by using off-axis electron holography. The analysis
      of the experimental data requires the knowledge of the mean inner potential (MIP)
      of the (Si,Ge) solid solution. The MIP was calculated using different models of
      isolated or bonded atoms, which are based on the interpolation of first principle
      data. The results are compared with structure modeling and related MIP
      calculations applying classical molecular dynamics (MD) simulations. For MD
      simulations bond order potentials were applied, which can take into consideration
      both electronic effects and elastic relaxations. The calculated mean inner
      potential is used to transform the phase shifts into thickness mapping for the
      reconstruction of the 3D island morphology. Both, phase shift due to dynamical
      electron diffraction and structural relaxation influence the resulting 3D
      reconstruction.

PMID- 23142754
TI  - Nickel release and surface characteristics of fine powders of nickel metal and
      nickel oxide in media of relevance for inhalation and dermal contact.
AB  - Differences in surface oxide characteristics and extent of nickel release have
      been investigated in two thoroughly characterized micron-sized (mainly <4 MUm)
      nickel metal powders and a nickel oxide bulk powder when immersed in two
      different synthetic fluids, artificial sweat (ASW-pH 6.5) and artificial
      lysosomal fluid (ALF-pH 4.5) for time periods up to 24h. The investigation shows
      significantly more nickel released from the nickel metal powders (<88%) compared
      to the NiO powder (<0.1%), attributed to differences in surface properties.
      Significantly more nickel was released from the nickel metal powder with a thin
      surface oxide predominantly composed of non-stoichiometric nickel oxide (probably
      Ni(2)O(3)), compared to the release from the nickel metal powder with a thicker
      surface oxide predominantly composed of NiO and to a lesser extent Ni(2)O(3) (88%
      and 25% release after 24 h in ALF, respectively). Significantly lower amounts of
      nickel were released from the nickel metal powders in ASW (2.2% and <1%,
      respectively). The importance of particle and surface characteristics for any
      reliable risk assessment is discussed, and generated data compared with
      literature findings on bioaccessibility (released fraction) of nickel from
      powders of nickel metal and nickel oxide, and massive forms of nickel metal and
      nickel-containing alloys.

PMID- 23142753
TI  - Dichlorodiphenyltrichloroethane (DDT), DDT metabolites and pregnancy outcomes.
AB  - Organochlorine pesticides (OCPs) are persistent endocrine disruptors. OCPs cross
      the placenta; this prenatal exposure has been associated with adverse pregnancy
      outcomes. We investigated associations between prenatal exposure to OCPs and
      gestational age and birth weight in 600 infants born between 1960 and 1963. The
      primary OCP was 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT), its
      primary metabolite, 1,1'-dichloro-2,2'-bis(p-chlorophenyl)ethylene (p,p'-DDE) and
      the contaminant, 1,1,1-trichloro-2-(p-chlorophenyl)-2-(o-chlorophenyl)-ethane
      (o,p'-DDT). Regression analysis indicated that for each natural log unit increase
      in p,p'-DDT, birth weight increased by 274 g (95% CI: 122, 425) when controlling
      for p,p'-DDE and o,p'-DDT. At a given level of p,p'-DDT exposure, o,p'-DDT and
      p,p'-DDE were associated with decreased birth weight. p,p'-DDE was negatively
      associated with length of gestation, controlling for p,p'-DDT and o,p'-DDT. These
      findings suggest opposing associations between exposure to p,p'-DDT and p,p'-DDE
      and birth weight. We did not find evidence to support mediation by maternal
      thyroid hormone status nor that the association differed by sex.

PMID- 23142755
TI  - Oxidative DNA damage of peripheral blood polymorphonuclear leukocytes,
      selectively induced by chronic arsenic exposure, is associated with extent of
      arsenic-related skin lesions.
AB  - There is increasing evidence that oxidative stress is an important risk factor
      for arsenic-related diseases. Peripheral blood leukocytes constitute an important
      defense against microorganisms or pathogens, while the research on the impact of
      chronic arsenic exposure on peripheral blood leukocytes is much more limited,
      especially at low level arsenic exposure. The purpose of the present study was to
      explore whether chronic arsenic exposure affects oxidative stress of peripheral
      blood leukocytes and possible linkages between oxidative stress and arsenic
      induced skin lesions. 75 male inhabitants recruited from an As-endemic region of
      China were investigated in the present study. The classification of arsenicosis
      was based on the degree of skin lesions. Arsenic levels were measured in drinking
      water and urine by Atomic Fluorescence Spectroscopy. Urinary 8-hydroxy-2'
      deoxyguanosine (8-OHdG) was tested by Enzyme-Linked Immunosorbent Assay. 8-OHdG
      of peripheral blood leukocytes was evaluated using immunocytochemical staining. 8
      OHdG-positive reactions were only present in polymorphonuclear leukocytes (PMNs),
      but not in monocytes (MNs). The 8-OHdG staining of PMN cytoplasm was observed in
      all investigated populations, while the 8-OHdG staining of PMN nuclei was
      frequently found along with the elevated amounts of cell debris in individuals
      with skin lesion. Urinary arsenic levels were increased in the severe skin lesion
      group compared with the normal group. No relationship was observed between
      drinking water arsenic or urine 8-OHdG and the degree of skin lesions. These
      findings indicated that the target and persistent oxidative stress in peripheral
      blood PMNs may be employed as a sensitive biomarker directly to assess adverse
      health effects caused by chronic exposure to lower levels of arsenic.

PMID- 23142756
TI  - Cytochrome P4501A induction in avian hepatocyte cultures exposed to
      polychlorinated biphenyls: comparisons with AHR1-mediated reporter gene activity
      and in ovo toxicity.
AB  - Avian-specific toxic equivalency factors (TEFs) were developed by the World
      Health Organization to simplify environmental risk assessments of dioxin-like
      compounds (DLCs), but TEFs do not account for differences in the toxic and
      biochemical potencies of DLCs among species of birds. Such variability may be due
      to differences in species sensitivity to individual DLCs. The sensitivity of
      avian species to DLCs was recently associated with the identity of amino acids
      324 and 380 in the aryl hydrocarbon receptor 1 (AHR1) ligand binding domain. A
      luciferase reporter gene (LRG) assay, measuring AHR1-mediated induction of a
      cytochrome P450 1A5 (CYP1A5) reporter gene, in combination with a species' AHR1
      ligand binding domain sequence, were also shown to predict avian species
      sensitivity to polychlorinated biphenyls (PCBs) and PCB relative potency in a
      given species. The goals of the present study were to (1) characterize the
      concentration-dependent effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and PCBs
      126, 77, 105 and 118 on induction of ethoxyresorufin O-deethylase (EROD) activity
      and CYP1A4/5 mRNA in chicken, ring-necked pheasant and Japanese quail embryo
      hepatocytes and (2) compare these in vitro results to those previously generated
      by the LRG assay and in ovo toxicity studies. EROD activity and CYP1A4/5 mRNA
      expression data support and complement the findings of the LRG assay. CYP1A
      enzyme activity and mRNA expression were significantly correlated both with
      luciferase activity and in ovo toxicity induced by PCBs. Relative potency values
      were generally similar between the LRG and EROD assays and indicate that the
      relative potency of some PCBs may differ among species.

PMID- 23142757
TI  - Validation of the proteasome as a therapeutic target in Plasmodium using an
      epoxyketone inhibitor with parasite-specific toxicity.
AB  - The Plasmodium proteasome has been suggested to be a potential antimalarial drug
      target; however, toxicity of inhibitors has prevented validation of this enzyme
      in vivo. We report a screen of a library of 670 analogs of the recent US Food and
      Drug Administration-approved inhibitor, carfilzomib, to identify compounds that
      selectively kill parasites. We identified one compound, PR3, that has significant
      parasite killing activity in vitro but dramatically reduced toxicity in host
      cells. We found that this parasite-specific toxicity is not due to selective
      targeting of the Plasmodium proteasome over the host proteasome, but instead is
      due to a lack of activity against one of the human proteasome subunits.
      Subsequently, we used PR3 to significantly reduce parasite load in Plasmodium
      berghei infected mice without host toxicity, thus validating the proteasome as a
      viable antimalarial drug target.

PMID- 23142758
TI  - Engagement of new castle disease virus (NDV) matrix (M) protein with charged
      multivesicular body protein (CHMP) 4 facilitates viral replication.
AB  - Newcastle disease virus (NDV) causes heavy economic losses to poultry industry
      across the globe every year. Although NDV matrix (M) protein is involved in virus
      budding and our previous data indicate that in ovo expression of M protein
      facilitates NDV replication, the underlying mechanism for the role of M protein
      in NDV replication is not clear. Using yeast two-hybrid system and
      immunoprecipitation approaches, we found that M protein interacted with host
      vacuolar sorting protein charged multivesicular body protein (CHMP) 4B and 4C. In
      addition, the colocalization of M protein and CHMP4B/C could be observed using a
      laser confocal scanning microscope. Knockdown of CHMP4B by siRNA or transient
      expression of CHMP4B/C dominant negative forms markedly inhibited NDV growth in
      DF-1 cells. Thus, cellular CHMP4s play a critical role in NDV replication.

PMID- 23142760
TI  - Factors implicated in the assessment of aminolevulinic acid-induced
      protoporphyrin IX fluorescence.
AB  - BACKGROUND: Photodynamic therapy and photodiagnosis of cancer requires
      preferential accumulation of fluorescent photosensitizers in tumors. Clinical
      evidence documents feasibility of ALA-based photodiagnosis for tumor detection.
      However, false positive results and large variations in fluorescence intensities
      are also reported. Furthermore, selective accumulation of fluorescent species of
      photosensitizers in tumor cell lines, as compared to normal ones, when cultured
      in vitro, is not always observed. To understand this discrepancy we analyzed the
      impact of various factors on the intensity of detected PpIX fluorescence.
      METHODS: Impacts of cell type, mitochondrial potential, cell-cell interactions
      and relocalization of PpIX among different cell types in co-cultures of different
      cell lines were analyzed by confocal microscopy and flow cytometry. Fluorescence
      spectroscopy was used to estimate absolute amounts of ALA-induced PpIX in
      individual cell lines. Immunofluorescence staining was applied to evaluate the
      ability of cell lines to produce collagen. RESULTS: Higher ALA-induced PpIX
      fluorescence in cancer cell lines as compared to normal ones was not detected by
      all the methods used. Mitochondrial activity was heterogeneous throughout the
      cell monolayers and could not be clearly correlated with PpIX fluorescence.
      Positive collagen staining was detected in all cell lines tested. CONCLUSIONS:
      Contrary to in vivo situation, ALA-induced PpIX production by cell lines in vitro
      may not result in higher PpIX fluorescence signals in tumor cells than in normal
      ones. We suggest that a combination of several properties of tumor tissue,
      instead of tumor cells only, is responsible for increased ALA-induced PpIX
      fluorescence in solid tumors. GENERAL SIGNIFICANCE: Understanding the reasons of
      increased ALA-induced PpIX fluorescence in tumors is necessary for reliable ALA
      based photodiagnosis, which is used in various oncological fields.

PMID- 23142762
TI  - Correlates of moderate-to-vigorous physical activity participation in adults with
      intellectual disabilities.
AB  - Adults with intellectual disabilities (ID) have low levels of physical activity
      and higher than average rates of related chronic health conditions. Understanding
      correlates of their physical activity participation may improve health promoting
      interventions. Forty-two adults with ID participated in a physical activity
      study. Physical activity knowledge and skills, awareness of recommendations and
      demographic characteristics were analyzed for their association with moderate-to
      vigorous physical activity (MVPA) participation measured by accelerometers. Five
      variables were significantly correlated with MVPA. Body mass index was inversely
      correlated with MVPA, and gender, job location, job tasks, and place of residence
      were all significantly associated with MVPA. Understanding correlates of physical
      activity in this population will help inform disability service and health
      promotion professionals in future research and health intervention design. 

PMID- 23142761
TI  - Absence of venous valves in mice lacking Connexin37.
AB  - Venous valves play a crucial role in blood circulation, promoting the one-way
      movement of blood from superficial and deep veins towards the heart. By
      preventing retrograde flow, venous valves spare capillaries and venules from
      being subjected to damaging elevations in pressure, especially during skeletal
      muscle contraction. Pathologically, valvular incompetence or absence of valves
      are common features of venous disorders such as chronic venous insufficiency and
      varicose veins. The underlying causes of these conditions are not well
      understood, but congenital venous valve aplasia or agenesis may play a role in
      some cases. Despite progress in the study of cardiac and lymphatic valve
      morphogenesis, the molecular mechanisms controlling the development and
      maintenance of venous valves remain poorly understood. Here, we show that in
      valved veins of the mouse, three gap junction proteins (Connexins, Cxs), Cx37,
      Cx43, and Cx47, are expressed exclusively in the valves in a highly polarized
      fashion, with Cx43 on the upstream side of the valve leaflet and Cx37 on the
      downstream side. Surprisingly, Cx43 expression is strongly induced in the non
      valve venous endothelium in superficial veins following wounding of the overlying
      skin. Moreover, we show that in Cx37-deficient mice, venous valves are entirely
      absent. Thus, Cx37, a protein involved in cell-cell communication, is one of only
      a few proteins identified so far as critical for the development or maintenance
      of venous valves. Because Cxs are necessary for the development of valves in
      lymphatic vessels as well, our results support the notion of common molecular
      pathways controlling valve development in veins and lymphatic vessels.

PMID- 23142763
TI  - Multiple symmetric lipomatosis type I in a female patient with neuropathy: no
      association with alcoholism or mitochondrial DNA m.8344A>G mutation.

PMID- 23142759
TI  - Optogenetic dissection of neural circuits underlying emotional valence and
      motivated behaviors.
AB  - The neural circuits underlying emotional valence and motivated behaviors are
      several synapses away from both defined sensory inputs and quantifiable motor
      outputs. Electrophysiology has provided us with a suitable means for observing
      neural activity during behavior, but methods for controlling activity for the
      purpose of studying motivated behaviors have been inadequate: electrical
      stimulation lacks cellular specificity and pharmacological manipulation lacks
      temporal resolution. The recent emergence of optogenetic tools provides a new
      means for establishing causal relationships between neural activity and behavior.
      Optogenetics, the use of genetically-encodable light-activated proteins, permits
      the modulation of specific neural circuit elements with millisecond precision.
      The ability to control individual cell types, and even projections between distal
      regions, allows us to investigate functional connectivity in a causal manner. The
      greatest consequence of controlling neural activity with finer precision has been
      the characterization of individual neural circuits within anatomical brain
      regions as defined functional units. Within the mesolimbic dopamine system,
      optogenetics has helped separate subsets of dopamine neurons with distinct
      functions for reward, aversion and salience processing, elucidated GABA neuronal
      effects on behavior, and characterized connectivity with forebrain and cortical
      structures. Within the striatum, optogenetics has confirmed the opposing
      relationship between direct and indirect pathway medium spiny neurons (MSNs), in
      addition to characterizing the inhibition of MSNs by cholinergic interneurons.
      Within the hypothalamus, optogenetics has helped overcome the heterogeneity in
      neuronal cell-type and revealed distinct circuits mediating aggression and
      feeding. Within the amygdala, optogenetics has allowed the study of intra
      amygdala microcircuitry as well as interconnections with distal regions involved
      in fear and anxiety. In this review, we will present the body of optogenetic
      studies that has significantly enhanced our understanding of emotional valence
      and motivated behaviors. This article is part of a Special Issue entitled
      Optogenetics (7th BRES).

PMID- 23142764
TI  - MYC2: the master in action.
AB  - Jasmonates (JAs) are plant hormones with essential roles in plant defense and
      development. The basic-helix-loop-helix (bHLH) transcription factor (TF) MYC2 has
      recently emerged as a master regulator of most aspects of the jasmonate (JA)
      signaling pathway in Arabidopsis. MYC2 coordinates JA-mediated defense responses
      by antagonistically regulating two different branches of the JA signaling pathway
      that determine resistance to pests and pathogens, respectively. MYC2 is required
      for induced systemic resistance (ISR) triggered by beneficial soil microbes while
      MYC2 function is targeted by pathogens during effector-mediated suppression of
      innate immunity in roots. Another notable function of MYC2 is the regulation of
      crosstalk between the signaling pathways of JA and those of other phytohormones
      such as abscisic acid (ABA), salicylic acid (SA), gibberellins (GAs), and auxin
      (IAA). MYC2 also regulates interactions between JA signaling and light,
      phytochrome signaling, and the circadian clock. MYC2 is involved in JA-regulated
      plant development, lateral and adventitious root formation, flowering time, and
      shade avoidance syndrome. Related bHLH TFs MYC3 and MYC4 also regulate both
      overlapping and distinct MYC2-regulated functions in Arabidopsis while MYC2
      orthologs act as 'master switches' that regulate JA-mediated biosynthesis of
      secondary metabolites. Here, we briefly review recent studies that revealed
      mechanistic new insights into the mode of action of this versatile TF.

PMID- 23142765
TI  - Temporal characterization of bacterial communities in a phytoremediation pilot
      plant aimed at decontaminating polluted sediments dredged from Leghorn harbor,
      Italy.
AB  - The AGRIPORT project (Agricultural Reuse of Polluted Dredged Sediments, Eco
      innovation EU Project n. ECO/08/239065) aims at developing a new technology for
      the treatment of polluted sediments dredged from the seabed of commercial ports
      through phytoremediation processes. Through plant activities and microorganism
      metabolisms, it is possible to recover dredged saline sediments by
      decontaminating them until an artificially prepared soil that is reusable in the
      terrestrial environment is obtained. This is an important advantage from the
      environmental point of view, and allows to partially solve one of the main
      problems of most commercial ports, that is the accumulation, storage and disposal
      of polluted dredged sediments. Considering that bacteria provide a significant
      contribution to phytoremediation process. Aim of the present study is the
      monitoring of temporal variation of microbial communities developing in an
      experimental phytoremediation plant during the decontamination process. The
      treatment plant consists of a sealed 80 m(3) basin that is filled with a mixture
      of dredged sediments (75%) and natural soil (25%). It was planted with three
      plant species, and has been properly cultivated and fertilized for two years.
      Terminal Restriction Fragment Length Polymorphism (T-RFLP) on 16S rRNA gene was
      used to study the composition of bacterial communities at different times and
      points in the basin. Cluster Analysis (CA) and Non Metric Multidimensional
      Scaling (NMDS) multivariate statistics were applied for data interpretation. At
      the onset, the bacterial communities were heterogeneous and discrete, reflecting
      those inherited from the sediment-soil mixture, from compost and from plant's
      rhizospheres. The communities' composition rapidly changed to become stabilized
      after one year.

PMID- 23142766
TI  - Oxidative stress adaptation with acute, chronic, and repeated stress.
AB  - Oxidative stress adaptation, or hormesis, is an important mechanism by which
      cells and organisms respond to, and cope with, environmental and physiological
      shifts in the level of oxidative stress. Most studies of oxidative stress
      adaption have been limited to adaptation induced by acute stress. In contrast,
      many if not most environmental and physiological stresses are either repeated or
      chronic. In this study we find that both cultured mammalian cells and the fruit
      fly Drosophila melanogaster are capable of adapting to chronic or repeated stress
      by upregulating protective systems, such as their proteasomal proteolytic
      capacity to remove oxidized proteins. Repeated stress adaptation resulted in
      significant extension of adaptive responses. Repeated stresses must occur at
      sufficiently long intervals, however (12-h or more for MEF cells and 7 days or
      more for flies), for adaptation to be successful, and the levels of both repeated
      and chronic stress must be lower than is optimal for adaptation to acute stress.
      Regrettably, regimens of adaptation to both repeated and chronic stress that were
      successful for short-term survival in Drosophila nevertheless also caused
      significant reductions in life span for the flies. Thus, although both repeated
      and chronic stress can be tolerated, they may result in a shorter life.

PMID- 23142767
TI  - Metallostasis in Alzheimer's disease.
AB  - 2012 has been another year in which multiple large-scale clinical trials for
      Alzheimer's disease (AD) have failed to meet their clinical endpoints. With the
      social and financial burden of this disease increasing every year, the onus is
      now on the field of AD researchers to investigate alternative ideas to deliver
      outcomes for patients. Although several major clinical trials targeting Abeta
      have failed, three smaller clinical trials targeting metal interactions with
      Abeta have all shown benefit for patients. Here we review the genetic,
      pathological, biochemical, and pharmacological evidence that underlies the metal
      hypothesis of AD. The AD-affected brain suffers from metallostasis, or fatigue of
      metal trafficking, resulting in redistribution of metals into inappropriate
      compartments. The metal hypothesis is built upon a triad of transition elements:
      iron, copper, and zinc. The hypothesis has matured from early investigations
      showing amyloidogenic and oxidative stress consequences of these metals;
      recently, disease-related proteins, APP, tau, and presenilin, have been shown to
      have major roles in metal regulation, which provides insight into the pathway of
      neurodegeneration in AD and illuminates potential new therapeutic avenues. 

PMID- 23142768
TI  - Protective effect of naringenin against acetaminophen-induced acute liver injury
      in metallothionein (MT)-null mice.
AB  - Naringenin is a natural flavonoid aglycone of naringin that has been reported to
      have a wide range of pharmacological properties, such as antioxidant activity and
      free radical scavenging capacity. This study was designed to examine the
      hepatoprotective effect of naringenin against acetaminophen (250 mg kg(-1), sc)
      in metallothionein (MT)-null mice. 42 SPF MT-knockout mice were used. Naringenin
      (200, 400, and 800 mg kg(-1), ig) was administered for 4 days before exposure to
      acetaminophen (250 mg kg(-1), sc). Liver injury was measured by serum alanine
      aminotransferase (ALT), aspartate aminotransferase (AST) and lactate
      dehydrogenase (LDH), as well as liver malondialdehyde (MDA). The glutathione-to
      oxidized glutathione ratio (GSH/GSSG) was also assessed. The evidence of liver
      injury induced by acetaminophen included not only a significant increase in the
      levels of serum ALT, AST, LDH and liver MDA, and also a significant decrease in
      GSH/GSSG. Pretreatment of mice with naringenin at 400 and 800 mg kg(-1) reversed
      the altered parameters. Such reversal effects were dose-dependent: ALT decreased
      78.62% and 98.03%, AST decreased 88.35% and 92.64%, LDH decreased 76.54% and
      81.63%, MDA decreased 48.59% and 66.27% at a dose of 400 and 800 mg kg(-1)
      respectively; GSH/GSSG increased 22.57% and 16.93% at a dose of 400 and 800 mg
      kg(-1) respectively. Histopathological observation findings were also consistent
      with these effects. Together, this study suggests that naringenin can potentially
      reverse the hepatotoxic damage of acetaminophen intoxication in MT-null mice.

PMID- 23142769
TI  - Increased thalamic phospholipid concentration evident in bipolar I disorder.
AB  - BACKGROUND: Bipolar disorder is characterised by changes in brain metabolites, as
      measured by (1)H-MRS. However, there is no consistent metabolic profile for
      bipolar disorder, which includes changes in N-acetyl-aspartate (NAA), choline
      metabolites and myo-inositol. The aim of the present paper is to add to this
      literature of (1)H-MRS, the metabolite profiles in bipolar disorder. METHODOLOGY:
      Nineteen individuals with euthymic bipolar I disorder and eight control
      participants were recruited for the present study. (1)H-MRS chemical shift
      imaging (CSI) was used to measure NAA, choline metabolites and myo-inositol of
      several bilateral brain areas potentially involved in bipolar disorder:
      hippocampal complexes, brain stem including the locus coeruleus, and thalami.
      RESULTS: Compared with healthy controls, individuals with bipolar I disorder
      showed increased choline metabolites in bilateral thalami and increased NAA in
      left hippocampus. The (1)H-MRS data were not influenced by age, symptom severity,
      or medication status. CONCLUSIONS: Our present findings suggest that individuals
      with bipolar I disorder have increased phospholipid concentration in the thalami
      and increased NAA concentration in the left hippocampus. While MRS data on
      bipolar data remain somewhat inconsistent, the findings here are consistent with
      other evidence supporting the hypothesis that dysfunctional thalamocortical
      gating plays a role in bipolar disorder.

PMID- 23142770
TI  - Clozapine regulation of p90RSK and c-Fos signaling via the ErbB1-ERK pathway is
      distinct from olanzapine and haloperidol in mouse cortex and striatum.
AB  - Treatment of the positive psychotic symptoms of schizophrenia with standard
      antipsychotic drugs (APDs) is ineffective in a proportion of cases. For these
      treatment resistant patients the alternative is the APD clozapine which is
      superior to other agents but carries serious side effects. Why clozapine is
      uniquely effective is unknown, but we have previously postulated may involve G
      protein coupled receptor (GPCR) and epidermal growth factor (EGF) receptor
      (ErbB1) transactivation signaling to the mitogen-activated protein kinase
      extracellular signal regulated kinase (MAPK-ERK) cascade. This was based upon
      clozapine induced initial down-regulation and delayed ErbB1 mediated activation
      of the cortical and striatal ERK response in vivo distinct from other APDs. This
      study investigated if modulation of the ErbB1-ERK1/2 pathway by clozapine,
      olanzapine and haloperidol affected expression of the ERK substrates p90RSK and c
      Fos, factors that regulate transcription of proteins associated with
      neuroplasticity and synapse formation in C57Bl/6 mice. In cortex and striatum,
      acute clozapine treatment induced biphasic p90RSK phosphorylation via MEK that
      paralleled ERK phosphorylation independent of EGF receptor blockade. By contrast,
      olanzapine and haloperidol caused p90RSK phosphorylation that was not concomitant
      with ERK signaling over a 24-hour period. For c-Fos, clozapine elevated
      expression 24h after administration, a timeframe consistent with ERK activation
      at 8h. Alternatively, haloperidol stimulation of c-Fos levels limited to the
      striatum was in accord with direct transcriptional regulation through ERK. The
      unique spatio-temporal expression of downstream nuclear markers of the ErbB1-ERK
      pathway invoked by clozapine may contribute to its effectiveness in treatment
      resistant schizophrenia.

PMID- 23142771
TI  - Single session contextual fear conditioning remains dependent on the hippocampus
      despite an increase in the number of context-shock pairings during learning.
AB  - We examined if the strength of contextual fear learning determines whether remote
      memories become independent of the hippocampus. Rats received 3 or 10 shocks in a
      single contextual fear conditioning session and then received sham or complete
      neurotoxic lesions of the hippocampus 7, 50, or 100 days later. Following
      recovery from surgery, the rats were returned to the conditioning context for a 5
      min retention test. During this test, freezing, complete immobility except for
      breathing, was used as an index of memory. Regardless of the learning-to-surgery
      interval, the rats with hippocampal damage from the 3-shock condition showed
      little and significantly less freezing than their respective control group,
      suggesting profound flat graded retrograde amnesia. Similarly, each group of
      hippocampal-damaged rats from the 10-shock condition froze significantly less
      than their respective control group. However, the rats that received hippocampal
      damage 50 days after learning froze significantly more than the rats that
      received the damage 7 days after learning. The latter gradient to the retrograde
      amnesia did not increase with more time as the freezing was not as high in the
      most remote memory group (100 days). Combined, these findings suggest that a
      contextual fear memory acquired in a single session under stronger learning
      parameters remains dependent on the hippocampus.

PMID- 23142772
TI  - Does exposure to conflict of interest policies in psychiatry residency affect
      antidepressant prescribing?
AB  - BACKGROUND: Academic medical institutions have instituted conflict of interest
      (COI) policies in response to concerns about pharmaceutical industry influence.
      OBJECTIVE: To determine whether exposure to COI policies during psychiatry
      residency training affects psychiatrists' antidepressant prescribing patterns
      after graduation. RESEARCH DESIGN: We used 2009 physician-level national
      administrative prescribing data from IMS Health for 1652 psychiatrists from 162
      residency programs. We used difference-in-differences estimation to compare
      antidepressant prescribing based on graduation before (2001) or after (2008) COI
      policy adoption across residency program groups with maximally, moderately, and
      minimally restrictive COI policies. The primary outcomes were shares of
      psychiatrists' prescribing of heavily promoted, brand reformulated, and brand
      antidepressants. RESULTS: Rates of prescribing heavily promoted, brand
      reformulated, and brand antidepressants in 2009 were lower among post-COI
      graduates than pre-COI graduates at all levels of COI restrictiveness. However,
      differences between pre-COI and post-COI graduates' prescribing of heavily
      promoted medications were larger for maximally restrictive programs than both
      minimally restrictive programs [-4.3 percentage points; 95% confidence interval
      (CI), -7.0, -1.6] and moderately restrictive programs (-3.6 percentage points;
      95% CI, -6.2, -1.1). The difference in prescribing reformulations was larger for
      maximally restrictive programs than minimally restrictive programs (-3.0
      percentage points; 95% CI, -5.3, -0.7). Results were consistent for prescribing
      of brand drugs. CONCLUSIONS: This study provides the first empirical evidence of
      the effects of COI policies. Our results suggest that COI policies can help
      inoculate physicians against persuasive aspects of pharmaceutical promotion.
      Further research should assess whether these policies affect other drug classes
      and physician specialties similarly.

PMID- 23142773
TI  - Recognition of the nonclassical MHC class I molecule H2-M3 by the receptor Ly49A
      regulates the licensing and activation of NK cells.
AB  - The development and function of natural killer (NK) cells is regulated by the
      interaction of inhibitory receptors of the Ly49 family with distinct peptide
      laden major histocompatibility complex (MHC) class I molecules, although whether
      the Ly49 family is able bind to other MHC class I-like molecules is unclear. Here
      we found that the prototypic inhibitory receptor Ly49A bound the highly conserved
      nonclassical MHC class I molecule H2-M3 with an affinity similar to its affinity
      for H-2D(d). The specific recognition of H2-M3 by Ly49A regulated the 'licensing'
      of NK cells and mediated 'missing-self' recognition of H2-M3-deficient bone
      marrow. Host peptide-H2-M3 was required for optimal NK cell activity against
      experimental metastases and carcinogenesis. Thus, nonclassical MHC class I
      molecules can act as cognate ligands for Ly49 molecules. Our results provide
      insight into the various mechanisms that lead to NK cell tolerance.

PMID- 23142774
TI  - Neutrophil infiltration during inflammation is regulated by PILRalpha via
      modulation of integrin activation.
AB  - Acute inflammatory responses are important in host defense, whereas dysregulated
      inflammation results in life-threatening complications. Here we found that paired
      immunoglobulin-like type 2 receptor alpha (PILRalpha), an inhibitory receptor
      containing immunoreceptor tyrosine-based inhibitory motifs (ITIMs), negatively
      regulated neutrophil infiltration during inflammation. Pilra(-/-) mice had
      increased neutrophil recruitment to inflammatory sites and were highly
      susceptible to endotoxin shock. Pilra(-/-) neutrophils showed enhanced
      transmigration ability and increased adhesion to the beta(2) integrin ligand ICAM
      1. PILRalpha expressed on neutrophils constitutively associated in cis with its
      ligands, resulting in clustering of PILRalpha during stimulation with a
      chemoattractant. Clustering of PILRalpha enhanced ITIM-mediated signaling, thus
      modulating beta(2) integrin inside-out activation. These data demonstrate that
      neutrophil recruitment in inflammatory responses is regulated by PILRalpha via
      modulation of integrin activation.

PMID- 23142776
TI  - Cubosomes containing the adjuvants imiquimod and monophosphoryl lipid A stimulate
      robust cellular and humoral immune responses.
AB  - New generation vaccines increasingly utilize highly purified peptides and
      proteins as the target antigen, however these are often poorly immunogenic. One
      of the most promising strategies for improving immunogenicity of such subunit
      vaccines is through incorporation into particulate carriers. Here we report the
      preparation, physicochemical characterization and in vivo immunological activity
      of cubosomes, a novel lipid-based nanostructured particulate carrier, modified to
      include the Toll-like receptor agonists monophosphoryl lipid A and imiquimod. The
      immunological activity of cubosome formulations was compared to that of liposome
      and alum formulations. Sustained release of the model antigen ovalbumin (Ova) was
      observed in vitro and in vivo from cubosomes. Cubosomes+adjuvants induced robust
      CD8+ and CD4+ T cell proliferation and interferon-gamma production, as well as
      the production of Ova-specific antibodies. Cubosomes+adjuvants were more
      efficient at generating Ova-specific cellular responses and were equally as
      effective in generating humoral responses when compared to liposomes+adjuvants
      and alum. Overall, the results show that cubosomes have the potential to act as
      effective sustained release vaccine delivery systems.

PMID- 23142775
TI  - The helicase DDX41 recognizes the bacterial secondary messengers cyclic di-GMP
      and cyclic di-AMP to activate a type I interferon immune response.
AB  - The induction of type I interferons by the bacterial secondary messengers cyclic
      di-GMP (c-di-GMP) or cyclic di-AMP (c-di-AMP) is dependent on a signaling axis
      that involves the adaptor STING, the kinase TBK1 and the transcription factor
      IRF3. Here we identified the heliase DDX41 as a pattern-recognition receptor
      (PRR) that sensed both c-di-GMP and c-di-AMP. DDX41 specifically and directly
      interacted with c-di-GMP. Knockdown of DDX41 via short hairpin RNA in mouse or
      human cells inhibited the induction of genes encoding molecules involved in the
      innate immune response and resulted in defective activation of STING, TBK1 and
      IRF3 in response to c-di-GMP or c-di-AMP. Our results suggest a mechanism whereby
      c-di-GMP and c-di-AMP are detected by DDX41, which forms a complex with STING to
      signal to TBK1-IRF3 and activate the interferon response.

PMID- 23142778
TI  - A highly selective fluorescence turn-on detection of cyanide based on the
      aggregation of tetraphenylethylene molecules induced by chemical reaction.
AB  - A new selective and sensitive fluorescence turn-on detection of CN(-) is reported
      by taking advantage of aggregation induced-emission (AIE) behavior of
      tetraphenylethylene units and the nucleophilic attack of CN(-) on the indolium
      group in compound 1.

PMID- 23142777
TI  - Toxicity in mice of lectin ebulin f present in dwarf Elderberry (Sambucus ebulus
      L.).
AB  - Dwarf elder fruits (Sambucus ebulus) contain the ribosome-inactivating lectin
      ebulin f structurally related to ricin. We investigated intraperitoneal toxicity
      of ebulin f in mice and found that it triggers specific derangement of the
      intestines. Ebulin f was much less toxic than ricin to mice when administered
      intraperitoneally. The targets were cells of the intestinal crypts, which
      underwent apoptosis. Small intestine crypts were more sensitive than large
      intestine crypts.

PMID- 23142779
TI  - Structure, function and regulation of Transcription Factor IIIA: From Xenopus to
      Arabidopsis.
AB  - Transcription Factor IIIA (TFIIIA) is specifically required for transcription of
      5S ribosomal RNA, an essential component of the ribosome. The TFIIIA protein,
      found in every organism, has been characterized in several species. It shows
      remarkably poor conservation of primary protein sequence, but all orthologues
      analyzed carry several C2H2-zinc fingers that are required for TFIIIA binding to
      both 5S ribosomal DNA (rDNA) and RNA (rRNA). Alignments of TFIIIA protein and 5S
      rRNA gene sequences suggest a parallel evolution of the transcription factor and
      its natural binding site, the internal control region of the 5S rRNA gene. We
      discuss here how TFIIIA expression and availability in the cell is tightly
      regulated at the transcriptional, post-transcriptional and post-translational
      level to ensure adequate amounts of TFIIIA protein depending on cell type and
      developmental stage. This article is part of a Special Issue entitled:
      Transcription by Odd Pols.

PMID- 23142780
TI  - Elimination of germinal-center-derived self-reactive B cells is governed by the
      location and concentration of self-antigen.
AB  - Secondary diversification of the B cell repertoire by immunoglobulin gene somatic
      hypermutation in the germinal center (GC) is essential for providing the high
      affinity antibody specificities required for long-term humoral immunity. While
      the risk to self-tolerance posed by inadvertent generation of self-reactive GC B
      cells has long been recognized, it has not previously been possible to identify
      such cells and study their fate. In the current study, self-reactive B cells
      generated de novo in the GC failed to survive when their target self-antigen was
      either expressed ubiquitously or specifically in cells proximal to the GC
      microenvironment. By contrast, GC B cells that recognized rare or tissue-specific
      self-antigens were not eliminated, and could instead undergo positive selection
      by cross-reactive foreign antigen and produce plasma cells secreting high
      affinity autoantibodies. These findings demonstrate the incomplete nature of GC
      self-tolerance and may explain the frequent association of cross-reactive, organ
      specific autoantibodies with postinfectious autoimmune disease.

PMID- 23142781
TI  - Nucleic acid-sensing Toll-like receptors are essential for the control of
      endogenous retrovirus viremia and ERV-induced tumors.
AB  - The genome of vertebrates contains endogenous retroviruses (ERVs) that are
      largely nonfunctional relicts of ancestral germline infection by exogenous
      retroviruses. However, in some mouse strains ERVs are actively involved in
      disease. Here we report that nucleic acid-recognizing Toll-like receptors 3, 7,
      and 9 (TLR 3, TLR7, and TLR9) are essential for the control of ERVs. Loss of TLR7
      function caused spontaneous retroviral viremia that coincided with the absence of
      ERV-specific antibodies. Importantly, additional TLR3 and TLR9 deficiency led to
      acute T cell lymphoblastic leukemia, underscoring a prominent role for TLR3 and
      TLR9 in surveillance of ERV-induced tumors. Experimental ERV infection induced a
      TLR3-, TLR7-, and TLR9-dependent group of "acute-phase" genes previously
      described in HIV and SIV infections. Our study suggests that in addition to their
      role in innate immunity against exogenous pathogens, nucleic acid-recognizing
      TLRs contribute to the immune control of activated ERVs and ERV-induced tumors.

PMID- 23142782
TI  - Neutrophils transport antigen from the dermis to the bone marrow, initiating a
      source of memory CD8+ T cells.
AB  - The bone marrow (BM) has been identified as a possible organ for T cell priming,
      yet the fundamental mechanisms of a polyclonal immune response in the BM remain
      unknown. We found that after intradermal injection of modified vaccinia Ankara
      virus, unexpected sources of newly primed polyclonal virus-specific CD8(+), but
      not CD4(+), T cells were localized in the BM and the draining lymph nodes (dLNs)
      prior to blood circulation. We identified neutrophils as the virus-carrier cells
      from the dermis to the BM. In both neutrophil-depleted and Ccr1(-/-) mice, virus
      specific BM CD8(+) responses were lost. Myeloid antigen-presenting cells were
      required for BM CD8(+) T cell priming. A systems biology analysis of dLN and BM
      virus-specific CD8(+) T cells revealed distinct transcriptional and
      multifunctional profiles for cells primed in each organ. We provide direct
      evidence for how antigen is transported to the BM, providing a source of virus
      specific memory CD8(+) T cells.

PMID- 23142784
TI  - Community-acquired neonatal and infant sepsis in developing countries: efficacy
      of WHO's currently recommended antibiotics--systematic review and meta-analysis.
AB  - OBJECTIVE: To review the aetiology and antibiotic resistance patterns of
      community-acquired sepsis in developing countries in infants where no clear focus
      of infection is clinically identified. To estimate the likely efficacy of WHO's
      recommended treatment for infant sepsis. DESIGN: A systematic review of the
      literature describing the aetiology of community-acquired neonatal and infant
      sepsis in developing countries. Using meta-analytical methods, susceptibility was
      determined to the antibiotic combinations recommended by WHO: (1)
      benzylpenicillin/ampicillin and gentamicin, (2) chloramphenicol and
      benzylpenicillin, and (3) third-generation cephalosporins. RESULTS: 19 studies
      were identified from 13 countries, with over 4000 blood culture isolates. Among
      neonates, Staphylococcus aureus, Klebsiella spp. and Escherichia coli accounted
      for 55% (39-70%) of culture positive sepsis on weighted prevalence. In infants
      outside the neonatal period, the most prevalent pathogens were S aureus, E coli,
      Klebsiella spp., Streptococcus pneumoniae and Salmonella spp., which accounted
      for 59% (26-92%) of culture positive sepsis. For neonates, penicillin/gentamicin
      had comparable in vitro coverage to third-generation cephalosporins (57% vs.
      56%). In older infants (1-12 months), in vitro susceptibility to
      penicillin/gentamicin, chloramphenicol/penicillin and third-generation
      cephalosporins was 63%, 47% and 64%, respectively. CONCLUSIONS: The high rate of
      community-acquired resistant sepsis-especially that caused by Klebsiella spp. and
      S aureus-is a serious global public health concern. In vitro susceptibility data
      suggest that third-generation cephalosporins are not more effective in treating
      sepsis than the currently recommended antibiotics, benzylpenicillin and
      gentamicin; however, with either regimen a significant proportion of bacteraemia
      is not covered. Revised recommendations for effective second-line antibiotics in
      neonatal and infant sepsis in developing countries are urgently needed.

PMID- 23142783
TI  - Inactivation of the enzyme GSK3alpha by the kinase IKKi promotes AKT-mTOR
      signaling pathway that mediates interleukin-1-induced Th17 cell maintenance.
AB  - Interleukin-1 (IL-1)-induced activation of the mTOR kinase pathway has major
      influences on Th17 cell survival, proliferation, and effector function. Via
      biochemical and genetic approaches, the kinases IKKi and GSK3alpha were
      identified as the critical intermediate signaling components for IL-1-induced AKT
      activation, which in turn activated mTOR. Although insulin-induced AKT activation
      is known to phosphorylate and inactivate GSK3alpha and GSK3beta, we found that
      GSK3alpha but not GSK3beta formed a constitutive complex to phosphorylate and
      suppress AKT activation, showing that a reverse action from GSK to AKT can take
      place. Upon IL-1 stimulation, IKKi was activated to mediate GSK3alpha
      phosphorylation at S21, thereby inactivating GSK3alpha to promote IL-1-induced
      AKT-mTOR activation. Thus, IKKi has a critical role in Th17 cell maintenance
      and/or proliferation through the GSK-AKT-mTOR pathway, implicating the potential
      of IKKi as a therapeutic target.

PMID- 23142785
TI  - Author response to Tebruegge, et al.

PMID- 23142786
TI  - Recurrent life-threatening sepsis in intestinal failure: transplantation or
      foster care?
AB  - Parenteral nutrition has transformed the outlook for patients with intestinal
      failure, but is associated with serious long-term complications, including
      catheter-related blood stream infection, liver disease and loss of venous access.
      Risks can be significantly reduced by strict adherence to management regimens,
      such as catheter-care protocols, but intestinal transplantation is indicated when
      complications threaten survival. The responsibility of home parenteral nutrition
      as an alternative to long-term hospitalisation is welcomed by many parents, but
      represents a huge burden of care that sometimes proves beyond their capacity. We
      report two children with recurrent life-threatening central venous catheter
      infections who were removed from the intestinal transplant list following virtual
      cessation of infective episodes after going into foster care. These cases raise
      important issues about the level of family support offered, the role of non
      compliance with treatment routines in relation to risk of complications, and how
      this should be assessed and monitored.

PMID- 23142787
TI  - Baclofen in community paediatric management of hypertonia.

PMID- 23142788
TI  - Mindfulness: top-down or bottom-up emotion regulation strategy?
AB  - The beneficial clinical effects of mindfulness practices are receiving increasing
      support from empirical studies. However, the functional neural mechanisms
      underlying these benefits have not been thoroughly investigated. Some authors
      suggest that mindfulness should be described as a 'top-down' emotion regulation
      strategy, while others suggest that mindfulness should be described as a 'bottom
      up' emotion regulation strategy. Current discrepancies might derive from the many
      different descriptions and applications of mindfulness. The present review aims
      to discuss current descriptions of mindfulness and the relationship existing
      between mindfulness practice and most commonly investigated emotion regulation
      strategies. Recent results from functional neuro-imaging studies investigating
      mindfulness training within the context of emotion regulation are presented. We
      suggest that mindfulness training is associated with 'top-down' emotion
      regulation in short-term practitioners and with 'bottom-up' emotion regulation in
      long-term practitioners. Limitations of current evidence and suggestions for
      future research on this topic are discussed.

PMID- 23142789
TI  - Effects of octylphenol and bisphenol A on the expression of calcium transport
      genes in the mouse duodenum and kidney during pregnancy.
AB  - Octylphenol (OP) is the degradative product of alkylphenol ethoxylates that are
      widely used to produce rubber, pesticides, and paints. Bisphenol A (BPA) is an
      organic compound with two functional phenol groups, and used for manufacturing
      polycarbonate plastic and epoxy resins, as well as other applications. OP and BPA
      are known as endocrine disruptors (EDs) with estrogenic activities, and may
      disturb natural calcium (Ca) metabolism. In the present study, the effects of OP
      and BPA on Ca levels in the serum and expression of Ca transport genes in the
      duodenum, and kidney were investigated in pregnant mice. Calbindin refers to
      several Ca-binding proteins originally described as vitamin D-dependent Ca
      binding factors in the intestine, and kidney of birds and mammals. Transient
      receptor potential cation channel, subfamily V, member 6 (TRPV6) and transient
      receptor potential cation channel, subfamily V, member 5 (TRPV5) are Ca entry
      channels responsible for Ca absorption in the kidney and intestine, respectively.
      From 6.5 to 16.5 day post coitus (dpc), pregnant mice were given oral doses of
      17alpha-ethynylestradiol (EE, 0.2mg/kg/day), BPA (5 or 50mg/kg/day), or OP (3,
      12, or 48 mg/kg/day) dissolved in corn oil. Samples of the duodenum, kidney, and
      blood were obtained from the mice on day 17.5 of pregnancy. Serum Ca levels were
      decreased in the groups treated with OP and BPA. The expression levels of Ca
      transport genes, TRPV5 and calbindin-D9k (CaBP-9k), in the kidney were decreased
      after treatment with OP and BPA. Duodenal expression of TRPV6 was also reduced by
      BPA and OP administration. CaBP-9k expression was differentially regulated by BPA
      and OP. Transcriptional and translational levels of CaBP-9k were decreased by EE
      and BPA but increased by a high dose of OP. Taken together, our findings
      demonstrate that OP and BPA regulated the expression of genes associated with Ca
      transport in the pregnant mice, which may result in the decreased serum Ca
      levels.

PMID- 23142790
TI  - Genotoxicity of polyvinylpyrrolidone-coated silver nanoparticles in BEAS 2B
      cells.
AB  - Silver nanoparticles (AgNPs) are widely utilized in various consumer products and
      medical devices, especially due to their antimicrobial properties. However,
      several studies have associated these particles with toxic effects, such as
      inflammation and oxidative stress in vivo and cytotoxic and genotoxic effects in
      vitro. Here, we assessed the genotoxic effects of AgNPs coated with
      polyvinylpyrrolidone (PVP) (average diameter 42.5+/-14.5 nm) on human bronchial
      epithelial BEAS 2B cells in vitro. AgNPs were dispersed in bronchial epithelial
      growth medium (BEGM) with 0.6 mg/ml bovine serum albumin (BSA). The AgNP were
      partially well-dispersed in the medium and only limited amounts (ca. 0.02 MUg
      Ag(+) ion/l) could be dissolved after 24h. The zeta-potential of the AgNPs was
      found to be highly negative in pure water but was at least partially neutralized
      in BEGM with 0.6 mg BSA/ml. Cytotoxicity was measured by cell number count
      utilizing Trypan Blue exclusion and by an ATP-based luminescence cell viability
      assay. Genotoxicity was assessed by the alkaline single cell gel electrophoresis
      (comet) assay, the cytokinesis-block micronucleus (MN) assay, and the chromosomal
      aberration (CA) assay. The cells were exposed to various doses (0.5-48 MUg/cm(2)
      corresponding to 2.5-240 MUg/ml) of AgNPs for 4 and 24 h in the comet assay, for
      48 h in the MN assay, and for 24 and 48 h in the CA assay. DNA damage measured by
      the percent of DNA in comet tail was induced in a dose-dependent manner after
      both the 4-h and the 24-h exposures to AgNPs, with a statistically significant
      increase starting at 16 MUg/cm(2) (corresponding to 60.8 MUg/ml) and doubling of
      the percentage of DNA in tail at 48 MUg/cm(2). However, no induction of MN or CAs
      was observed at any of the doses or time points. The lack of induction of
      chromosome damage by the PVP-coated AgNPs is possibly due to the coating which
      may protect the cells from direct interaction with the AgNPs, either by reducing
      ion leaching from the particles or by causing extensive agglomeration of the
      nanoparticles, with a possible reduction of the cellular uptake.

PMID- 23142791
TI  - Toxicogenomic biomarkers for renal papillary injury in rats.
AB  - Renal papillary injury is a common side effect observed during nonclinical and
      clinical investigations in drug development. The present study aimed to identify
      genomic biomarkers for early and sensitive detection of renal papillary injury in
      rats. We hypothesized that previously identified genomic biomarkers for tubular
      injury might be applicable for the sensitive detection of papillary injury in
      rats. We selected 18 genes as candidate biomarkers for papillary injury based on
      previously published studies and analyzed their expression profiles by RT-PCR in
      each kidney region, namely the cortex, cortico-medullary junction, and papilla in
      various nephrotoxicity models. Comparative analysis of gene expression profiles
      revealed that some genes were commonly upregulated or downregulated in the renal
      papilla, reflecting papillary injuries induced by 2-bromoethylamine hydrobromide,
      phenylbutazone, or n-phenylanthranilic acid. By applying receiver operator
      characteristics analysis, six candidate biomarkers were identified and their
      usefulness was confirmed by using an independent data set. The three top-ranked
      genes, Timp1, Igf1, and Lamc2, exhibited the best prediction performance in an
      external data set with area under the curve (AUC) values of greater than 0.91. An
      optimized support vector machine model consisting of three genes achieved the
      highest AUC value of 0.99. In conclusion, even though definitive validation
      studies are required for the establishment of their usefulness and reliability,
      these identified genes may prove to be the most promising candidate genomic
      biomarkers of renal papillary injury in rats.

PMID- 23142792
TI  - Bisphenol A exposure increases liver fat in juvenile fructose-fed Fischer 344
      rats.
AB  - BACKGROUND: Prenatal exposure to bisphenol A (BPA) has been shown to induce
      obesity in rodents. To evaluate if exposure also later in life could induce
      obesity or liver damage we investigated these hypothesises in an experimental rat
      model. METHODS: From five to fifteen weeks of age, female Fischer 344 rats were
      exposed to BPA via drinking water (0.025, 0.25 or 2.5 mg BPA/L) containing 5%
      fructose. Two control groups were given either water or 5% fructose solution.
      Individual weight of the rats was determined once a week. At termination magnetic
      resonance imaging was used to assess adipose tissue amount and distribution, and
      liver fat content. After sacrifice the left perirenal fat pad and the liver were
      dissected and weighed. Apolipoprotein A-I in plasma was analyzed by western blot.
      RESULTS: No significant effects on body weight or the weight of the dissected fad
      pad were seen in rats exposed to BPA, and MRI showed no differences in total or
      visceral adipose tissue volumes between the groups. However, MRI showed that
      liver fat content was significantly higher in BPA-exposed rats than in fructose
      controls (p=0.04). BPA exposure also increased the apolipoprotein A-I levels in
      plasma (p<0.0001). CONCLUSION: We found no evidence that BPA exposure affects fat
      mass in juvenile fructose-fed rats. However, the finding that BPA in combination
      with fructose induced fat infiltration in the liver at dosages close to the
      current tolerable daily intake (TDI) might be of concern given the widespread use
      of this compound in our environment.

PMID- 23142793
TI  - Neo-epitope tissue transglutaminase autoantibodies as a biomarker of the gluten
      sensitive skin disease--dermatitis herpetiformis.
AB  - BACKGROUND: The deamidated gliadin peptides (DGP) cross linked to human tissue
      transglutaminase (tTg) comprises a novel neo-epitope structure (Neo-tTg) for
      serological screening of celiac disease (CD). Our aim is to verify anti-Neo-tTg
      IgA and IgG in adults with dermatitis herpetiformis (DH). METHODS: Multi-centric
      retrospective evaluation of the IgA/G autoantibodies in sera of DH patients on a
      regular diet (n=40) and a gluten restricted diet (GRD, n=53) and control adults
      with autoimmune skin diseases (n=107) by ELISA. RESULTS: The sensitivities of
      Celicheck Neo IgA/G (76%, 95% CI 67-84%) and the Neo tTg-A (85%, 95% CI 70-97%)
      ELISA were significantly greater than that of tTg-A (56%, 95% CI 46-67%), eTg-A
      (62%, 95% CI 52-72%), DGP-A (55%, 95% CI 55-65%), DGP-G (61%, 95% CI 51-71%),
      Glia-A (55%, 95% CI 45-65%) and Glia-G (56%, 95% CI 46-66%) ELISA. The
      specificities of all 8 ELISA were in the range of 90-100%. The area under the
      curve (AUC) of receiver operator characteristic curve (ROC) for the two Neo-tTg
      ELISA (0.863 and 0.949) were higher than the AUCs for ROCs of tTg, DGP and eTG
      ELISA (range between 0.657 and 0.783). The autoantibody levels of DH patients on
      a normal diet were significantly higher than those on GRD in the Celicheck Neo
      IgA/IgG, NeotTg-A; tTg-A and the eTg-A; ELISA (p<0.01) and of no significance in
      the DGP and Gliadin ELISA. CONCLUSION: Neo-epitope IgA autoantibodies represent a
      new and sensitive serological marker of DH.

PMID- 23142794
TI  - KAI2- and MAX2-mediated responses to karrikins and strigolactones are largely
      independent of HY5 in Arabidopsis seedlings.
AB  - Karrikins are butenolide compounds released from burning vegetation that
      stimulate seed germination and enhance seedling photomorphogenesis.
      Strigolactones are structurally similar plant hormones that regulate shoot and
      root development, and promote the germination of parasitic weed seeds. In
      Arabidopsis, the F-box protein MAX2 is required for responses to karrikins and
      strigolactones, and the alpha/beta hydrolase KAI2 is necessary for responses to
      karrikins. Both MAX2 and KAI2 are essential for normal light-dependent seedling
      development. The bZIP transcription factor HY5 acts downstream of multiple
      photoreceptors and promotes photomorphogenesis, but its relationship with MAX2
      and KAI2 in terms of seedling development and responses to karrikins and
      strigolactones is poorly defined. Here, we demonstrate that HY5 action is
      genetically separable from that of MAX2 and KAI2. While hy5 mutants have weak
      hypocotyl elongation responses to karrikins and the artificial strigolactone
      GR24, they have normal transcriptional responses, suggesting that HY5 is not
      involved in perception or action of karrikins or strigolactones. Furthermore, we
      show that overexpression of KAI2 is sufficient to enhance responses to both
      karrikins and GR24 in wild-type seedlings, and that KAI2 overexpression partially
      suppresses the hy5 long hypocotyl phenotype. These results suggest that KAI2 and
      MAX2 define a regulatory pathway that largely operates independently of HY5 to
      mediate seedling responses to abiotic signals such as smoke and light.

PMID- 23142795
TI  - Effects of Withania somnifera on the growth and virulence properties of
      Streptococcus mutans and Streptococcus sobrinus at sub-MIC levels.
AB  - The aim of this study was to evaluate the effect of the methanol extract of
      Withania somnifera (MEW) on the growth and virulence properties of Streptococcus
      mutans and Streptococcus sobrinus at sub-minimum inhibitory concentration (MIC)
      levels and to identify the main components of MEW. First, antibacterial activity
      of MEW against oral bacteria was determined using a micro-dilution method. Then,
      the effect of MEW on the growth of S. mutans and S. sobrinus was investigated at
      sub-MIC levels. To test the effect of MEW on the virulence properties of S.
      mutans and S. sobrinus, assays for acid production, acid tolerance, and biofilm
      formation were performed at sub-MIC levels. A GC-MS analysis for the main
      components of MEW was also carried out. MEW showed a broad antibacterial range
      against oral bacteria (MIC: 0.125-2 mg/mL). At sub-MIC levels, MEW dose
      dependently increased doubling times of S. mutans and S. sobrinus up to 258% and
      400%, respectively. Furthermore, MEW inhibited acid production, acid tolerance,
      and biofilm formation of S. mutans and S. sobrinus at sub-MIC levels. The GC-MS
      analysis revealed the presence of mono- and disaccharides, sugar alcohols, and
      organic acids as main components. These data suggest that MEW might be useful for
      restraining physiological activities of cariogenic bacteria.

PMID- 23142796
TI  - An Italian association study and meta-analysis with previous GWAS confirm WNT4,
      CDKN2BAS and FN1 as the first identified susceptibility loci for endometriosis.
AB  - BACKGROUND: Although endometriosis may benefit from primary prevention measures,
      the epidemiological risk factors identified are equivocal. Two genome-wide
      association studies (GWAS) have been conducted for endometriosis in two different
      ethnic populations but results are still to be replicated consistently and across
      various ethnicities. To confirm the association of GWAS-derived susceptibility
      loci, we conducted a replication Italian case-control study and a meta-analysis.
      METHODS: An independent set of 305 laparoscopically-proven endometriosis patients
      and 2710 controls were recruited. Four SNPs-CDKN2BAS rs1333049, rs7521902 close
      to WNT4, rs12700667 in an inter-genic region on 7p15.2 and fibronectin 1
      rs1250248-were selected for this association study. RESULTS: Rs1333049 risk
      allele G frequency resulted significantly higher in endometriosis patients
      compared with controls (OR 1.32, 95% CI 1.11 to 1.57), confirming the role of
      this locus also in the Caucasian population. The meta-analysis showed that
      rs7521902 was associated with endometriosis at a genome-wide significance
      (p(meta)=2.23*10(-9)) while for rs1250248, a genome-wide significant p(meta)
      value of 3.89*10(-9) was detected only in association with severe forms. An
      epistatic interaction between rs7521902 and rs1250248 (OR 1.56, p=1.19*10(-2))
      was found especially in presence of ovarian disease (OR=2.15, p=3.12*10(-4)).
      CONCLUSIONS: We confirm WNT4, CDKN2BAS and FN1 as the first identified common
      loci for endometriosis.

PMID- 23142797
TI  - Human breast adenocarcinoma cytotoxicity and modulation of 7,12
      dimethylbenz[a]anthracene-induced mammary carcinoma in Balb/c mice by Acacia
      catechu (L.f.) Wild heartwood.
AB  - OBJECTIVE: The chemopreventive potential of (+)-catechin-rich extract of Acacia
      catechu (L.f.) Willd. heartwood (AQCE) was evaluated against human breast
      adenocarcinoma cell line (MCF-7) and 7,12-dimethylbenz[a]anthracene (DMBA)
      induced mammary carcinoma in Balb/c mice. METHODS: Cell cytotoxicity was
      investigated using different colorimetric assays. Apoptosis was observed using
      diphenylamine assay and fluorescent microscopy. AQCE was further evaluated for
      antitumor activity against DMBA-induced mammary carcinoma. The levels of tumor
      markers and oxidative stress were measured. Furthermore, level of transcription
      factors was measured by enzyme-linked immunosorbent assay. RESULTS: The results
      showed that administration of AQCE showed a dose-dependent growth inhibition
      response and DNA fragmentation in MCF-7 cells. Tumor multiplicity was
      significantly decreased to 42.91% with AQCE when compared with DMBA-treated
      animals. The levels of tumor markers such as total sialic acid and lipid
      associated sialic acid were substantially increased after DMBA treatment.
      However, AQCE treatment restored tumor markers level. AQCE also significantly
      reduced elevated levels of nitrite and malondialdehyde in DMBA-treated animals.
      Additionally, AQCE also increased the activities of antioxidant enzymes, viz.,
      catalase, superoxide dismutase, total thiol, reduced glutathione, protein thiol,
      glutathione peroxidase, glutathione reductase, and glutathione-S-transferase in
      the mammary tissue and liver mitochondria of DMBA-administered animals.
      Significant increase in the protein levels of p53, c-jun, and p65 were observed
      in DMBA-treated mice, whereas less expression was observed in AQCE-treated
      animals. Eventually, AQCE also significantly improved body weight and maintained
      the mammary tissue architecture in normal range. CONCLUSIONS: The present data
      strongly suggest that anticancer potentiality of (+)-catechin-rich AQCE may be
      attributable to its ability to positively modulate tumor markers as well as the
      antioxidant system that could decompose the peroxides and, thereby, offer a
      protection against lipid peroxidation and linked to the expression of
      transcription factors during DMBA-induced mammary carcinoma.

PMID- 23142798
TI  - Effect of Withania somnifera (Ashwagandha) on the development of chemotherapy
      induced fatigue and quality of life in breast cancer patients.
AB  - Hypothesis. Withania somnifera is an herb with antioxidant, anti-inflammatory,
      anticancer, antistress, and adaptogenic properties. Previous studies have shown
      its antistress effects in animals. Traditional Indian medicine has used it for
      centuries to alleviate fatigue and improve general well-being. METHODS: This is
      an open-label prospective nonrandomized comparative trial on 100 patients with
      breast cancer in all stages undergoing either a combination of chemotherapy with
      oral Withania somnifera or chemotherapy alone. The chemotherapy regimens were
      either taxotere, adriamycin, and cyclophosphamide or 5-fluorouracil, epirubicin,
      and cyclophosphamide. Withania somnifera root extract was administered to
      patients in the study group at a dose of 2 g every 8 hours, throughout the course
      of chemotherapy. The quality-of-life and fatigue scores were evaluated before,
      during, and on the last cycles of chemotherapy using the EORTC QLQ-C30 (Version
      3), Piper Fatigue Scale (PFS), and Schwartz Cancer Fatigue Scale (SCFS-6).
      RESULTS: The median age distributions in the study and control arm were 51 years
      (range = 36-70) and 50.5 years (range = 32-71), respectively. The majority (77%)
      of patients had stage II and III disease. Patients in the control arm experienced
      statistically significant higher estimated marginal means of fatigue score
      compared with the study group (P < .001 PFS, P < .003 SCFS-6). Furthermore,
      various symptom scales of the EORTC QLQ-C30 were statistically significant in 7
      out of 18 symptoms in the intervention group compared with the control group (P <
      .001). The 24-month overall survival for all stages in study and control group
      patients were 72% versus 56%, respectively; however, the result was not
      significant (P = .176), at a median follow-up duration of 26 months. CONCLUSIONS:
      Withania somnifera has potential against cancer-related fatigue, in addition to
      improving the quality of life. However, further study with a larger sample size
      in a randomized trial is warranted to validate our findings.

PMID- 23142799
TI  - Vibrational spectroscopic observation of ice dewetting on MgO(001).
AB  - The properties of the interfacial water monolayer on MgO(001) during growth of
      multilayer ice and, in particular, the dewetting of crystalline ice on MgO(001)
      are revealed by vibrational sum frequency generation and infrared reflection
      absorption spectroscopy.

PMID- 23142800
TI  - Centrifugal gas-phase transition magnetophoresis (GTM)--a generic method for
      automation of magnetic bead based assays on the centrifugal microfluidic platform
      and application to DNA purification.
AB  - Transportation of magnetic beads between different reagents plays a crucial role
      in many biological assays e.g. for purification of biomolecules or cells where
      the beads act as a mobile solid support. Therefore, usually a complex set-up
      either for fluidic processing or for manipulation of magnetic beads is required.
      To circumvent these drawbacks, we present a facile and automated method for the
      transportation of magnetic beads between multiple microfluidic chambers on a
      centrifugal microfluidic cartridge "LabDisk". The method excels by requiring only
      one stack of stationary permanent magnets, a specific microfluidic layout without
      actively controlled valves and a predefined frequency protocol for rotation of
      the LabDisk. Magnetic beads were transported through three fluidically separated
      chambers with a yield of 82.6% +/- 3.6%. Bead based DNA purification from a
      dilution series of a Listeria innocua lysate and from a lambda phage DNA standard
      was demonstrated where the three chambers were used for binding, washing and
      elution of DNA. Recovery of L. innocua DNA was up to 68% +/- 24% and for lambda
      phage DNA 43% +/- 10% compared to manual reference purification in test tubes.
      Complete purification was conducted automatically within 12.5 min. Since all
      reagents can be preloaded onto the LabDisk prior to purification, no further
      hands-on steps are required during processing. Due to its modular and generic
      character, the presented method could also be adapted to other magnetic bead
      based assays e.g. to immunoassays or protein affinity purification, solely
      requiring the adjustment of number and volumes of the fluidic chambers.

PMID- 23142801
TI  - Efficient cultivation of neural stem cells with controlled delivery of FGF-2.
AB  - Neural stem cells (NSCs) raised the hope for cell-based therapies in human
      neurodevelopmental and neurodegenerative diseases. Current research strategies
      aim to isolate, enrich, and propagate homogeneous populations of neural stem
      cells. Unfortunately, several concerns with NSC cultures currently may limit
      their therapeutic promise. Exhaustion of growth factors and/or their uncontrolled
      release with burst and fall in their concentration may greatly affect the in
      vitro behavior of NSCs. In this context, we investigate whether a device
      containing heparan sulfate (HS), which is a co-factor in growth factor-mediated
      cell proliferation and differentiation, could potentiate and prolong the delivery
      of fibroblast growth factor-2 (FGF-2) and thus improve in vitro NSC cultivation.
      We demonstrated that NSCs cultivated in media with a controlled release of FGF-2
      from a polyelectrolyte polymer showed a higher proliferation rate, and reduced
      apoptosis and senescence. In these experimental conditions NSCs preserve their
      stemness properties for a longer period of time compared with controls. Also of
      interest is that cell fate properties are conserved as well. The controlled
      release of FGF-2 reduced the level of oxidative stress and this is associated
      with a lower level of damaged DNA. This result may explain the reduced level of
      senescence and apoptosis in NSCs cultivated in the presence of hydrogel-releasing
      FGF-2.

PMID- 23142802
TI  - Autophagy and mesenchymal cell fibrogenesis.
AB  - Autophagy is a catabolic pathway essential for cellular energy homeostasis that
      involves the self-degradation of intracellular components in lysosomes. This
      process has been implicated in the pathophysiology of many human disorders,
      including infection, cancer, and fibrosis. Autophagy is also recognized as a
      mediator of survival and proliferation, and multiple pathways induce autophagy
      under conditions of cellular stress, including nutrient and energy depletion.
      High autophagic activity has been detected in fibrogenic cells from several
      tissues; however the role of autophagy in fibrogenesis and mesenchymal cells
      varies greatly in different tissues and settings, with contributions uncovered to
      energy metabolism and collagen turnover by fibrogenic cells. Because several
      chemical modulators of autophagy have already been identified, autophagy
      regulation constitutes a potential target for antifibrotic therapy. This article
      is part of a Special Issue entitled: Fibrosis: Translation of basic research to
      human disease.

PMID- 23142803
TI  - Marrow adiposity recovery after early zoledronic acid treatment of glucocorticoid
      induced bone loss in rabbits assessed by magnetic resonance spectroscopy.
AB  - BACKGROUND: Although there is an inverse relationship between bone mass and
      marrow adiposity, the reversal function of zoledronic acid (ZOL) on increased
      marrow fat has not been studied. The aim of our study is to use the 3T magnetic
      resonance spectroscopy (MRS) to characterize the dynamical change process of the
      marrow fat responding to early ZOL treatment in the rabbit model with
      glucocorticoid-induced bone loss. METHODS: Fifteen 20-week-old female New Zealand
      White rabbits were randomized to control group, methylprednisolone (MPS) group,
      and MPS+ZOL group equally. Bone mineral density (BMD) and marrow fat fraction
      (FF) at L3-L4 vertebrae and left proximal femur were measured by Dual-energy X
      ray absorptiometry and MRS at week 0, 4, 8, and 12. The animals were euthanized
      at the end of our experiment and their left femurs were dissected out for the
      histopathological examination. RESULTS: The MPS group demonstrated a remarkable
      increase in FF but a reduction in BMD compared with the controls at week 4 and 8,
      respectively (P<0.05 for all). Early treatment of ZOL can inhibit bone
      degeneration, although the bone mass would not recover to its original level. FF
      in MPS group exhibited a dramatic increase over time, with an increased FF
      variation (+31.6%, P=0.009) at week 4 from baseline and it was maintained until
      week 12 (+75.2%, P<0.001). In MPS+ZOL group, the FF returned to baseline value
      after the ZOL treatment. Comparing with the controls, larger marrow adipocyte
      density, the mean of the adipocyte diameter, and the percentage area of the
      adipocyte were observed in the MPS group (P<0.05 for all), whereas there were no
      significant differences in quantitative parameters of marrow adipocytes between
      the ZOL-treated group and the normal rabbits. CONCLUSION: An increase of the
      marrow adiposity is synchronized with the deterioration of the MPS-induced bone
      mass. A single dose of early ZOL can reverse the marrow adiposity to its original
      level completely.

PMID- 23142804
TI  - Longitudinal in vivo imaging of bone formation and resorption using fluorescence
      molecular tomography.
AB  - Bone research often focuses on anatomical imaging of the bone microstructure, but
      in order to gain better understanding in how bone remodeling is modulated through
      interventions also bone formation and resorption processes should be
      investigated. With this in mind, the purpose of this study was to establish a
      longitudinal in vivo imaging approach of bone formation and resorption using
      fluorescence molecular tomography (FMT). In this study the reproducibility,
      accuracy and sensitivity of FMT for bone imaging were assessed by performing
      longitudinal measurements with FMT and comparing it to in vivo micro-computed
      tomography on a set of control mice, and mice in which load-adaptation was
      induced in the sixth caudal vertebra. The precision error for FMT measurements,
      expressed as coefficient of variation, was smaller than 16%, indicating
      acceptable reproducibility. A correlation was found between bone resorption
      measured with FMT and bone resorption rate measured with in vivo micro-computed
      tomography only over the first 14days (R=0.81, p<0.01), but not between bone
      formation measured with FMT and bone formation rate measured with in vivo micro
      CT. Bone formation measured by FMT was 89-109% greater (p<0.05) for mice
      subjected to mechanical loading than control mice. Bone resorption was 5-8%
      lower, but did not reach a significant difference between groups, indicating
      moderate sensitivity for FMT. In conclusion, in vivo FMT in mouse tail bones is
      feasible but needs to be optimized for monitoring load adaptation in living mice.

PMID- 23142805
TI  - Higher prevalence of morphometric vertebral fractures in patients with recent
      coronary events independently of BMD measurements.
AB  - Cardiovascular disease and osteoporosis are important causes of morbi-mortality
      in the elderly and may be mutually related. Low bone mineral density (BMD) may be
      associated with increased risk of cardiovascular events. We investigated the
      prevalence of low bone mass and fractures in metabolic syndrome patients with
      acute coronary events. A case-control study was conducted with 150 individuals
      (30-80years-old) with metabolic syndrome. Seventy-one patients had had an acute
      coronary syndrome episode in the last 6months (cases) and the remaining 79 had no
      coronary event (controls). Cases and controls were matched for gender, BMI and
      age. DXA measurements and body composition were performed while spine radiographs
      surveyed for vertebral fractures and vascular calcification. Biochemical bone and
      metabolic parameters were measured in all patients. No statistically significant
      difference in BMD and the prevalence of osteopenia, osteoporosis and non
      vertebral fractures was observed between cases and controls. The prevalence of
      vertebral fractures and all fractures was higher in the cases (14.1 versus 1.3%,
      p=0.003 and 22.5versus7.6%, p=0.010, respectively). Male gender (OR=0.22 95% CI
      0.58 to 0.83, p=0.026) and daily intake of more than 3 portions of dairy products
      (OR=0.19 95% CI 0.49 to 0.75, p=0.017) were associated with lower prevalence of
      fractures. Cases had higher risk for fractures (OR=4.97, 95% CI 1.17 to 30.30,
      p=0.031). Bone mass and body composition parameters were not associated with
      cardiovascular risk factors or bone mineral metabolism. Patients with fragility
      fractures had higher OPG serum levels than those without fractures (p<0.001). Our
      findings demonstrated that patients with recent coronary events have a higher
      prevalence of vertebral fractures independently of BMD.

PMID- 23142806
TI  - Reduced bone breakage and increased bone strength in free range laying hens fed
      omega-3 polyunsaturated fatty acid supplemented diets.
AB  - INTRODUCTION: The omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) are the
      immediate precursors to a number of important mediators of immunity, inflammation
      and bone function, with products of omega-6 generally thought to promote
      inflammation and favour bone resorption. Western diets generally provide a 10 to
      20-fold deficit in omega-3 PUFAs compared with omega-6, and this is thought to
      have contributed to the marked rise in incidence of disorders of modern human
      societies, such as heart disease, colitis and perhaps osteoporosis. Many of our
      food production animals, fed on grains rich in omega-6, are also exposed to a
      dietary deficit in omega-3, with perhaps similar health consequences. Bone
      fragility due to osteoporotic changes in laying hens is a major economic and
      welfare problem, with our recent estimates of breakage rates indicating up to 95%
      of free range hens suffer breaks during lay. METHODS: Free range hens housed in
      full scale commercial systems were provided diets supplemented with omega-3 alpha
      linolenic acid, and the skeletal benefits were investigated by comparison to
      standard diets rich in omega-6. RESULTS: There was a significant 40-60% reduction
      in keel bone breakage rate, and a corresponding reduction in breakage severity in
      the omega-3 supplemented hens. There was significantly greater bone density and
      bone mineral content, alongside increases in total bone and trabecular volumes.
      The mechanical properties of the omega-3 supplemented hens were improved, with
      strength, energy to break and stiffness demonstrating significant increases.
      Alkaline phosphatase (an osteoblast marker) and tartrate-resistant acid
      phosphatase (an osteoclast marker) both showed significant increases with the
      omega-3 diets, indicating enhanced bone turnover. This was corroborated by the
      significantly lower levels of the mature collagen crosslinks, hydroxylysyl
      pyridinoline, lysyl pyridinoline and histidinohydroxy-lysinonorleucine, with a
      corresponding significant shift in the mature:immature crosslink ratio.
      CONCLUSIONS: The improved skeletal health in laying hens corresponds to as many
      as 68million fewer hens suffering keel fractures in the EU each year. The
      biomechanical and biochemical evidence suggests that increased bone turnover has
      enhanced the bone mechanical properties, and that this may suggest potential
      benefits for human osteoporosis.

PMID- 23142807
TI  - Activation of prostaglandin E receptor 4 triggers secretion of gut hormone
      peptides GLP-1, GLP-2, and PYY.
AB  - Prostaglandins E1 and E2 are synthesized in the intestine and mediate a range of
      gastrointestinal functions via activation of the prostanoid E type (EP) family of
      receptors. We examined the potential role of EP receptors in the regulation of
      gut hormone secretion from L cells. Analysis of mRNA expression in mouse
      enteroendocrine GLUTag cells demonstrated the abundant expression of EP4
      receptor, whereas expression of other EP receptors was much lower. Prostaglandin
      E1 and E2, nonselective agonists for all EP receptor subtypes, triggered glucagon
      like peptide 1 (GLP-1) secretion from GLUTag cells, as did the EP4-selective
      agonists CAY10580 and TCS2510. The effect of EP4 agonists on GLP-1 secretion was
      blocked by incubation of cells with the EP4-selective antagonist L161,982 or by
      down-regulating EP4 expression with specific small interfering RNA. Regulation of
      gut hormone secretion with EP4 agonists was further studied in mice.
      Administration of EP4 agonists to mice produced a significant elevation of plasma
      levels of GLP-1, glucagon like peptide 2 (GLP-2) and peptide YY (PYY), whereas
      gastric inhibitory peptide (GIP) levels were not increased. Thus, our data
      demonstrate that activation of the EP4 receptor in enteroendocrine L cells
      triggers secretion of gut hormones.

PMID- 23142808
TI  - Obesity-related alterations in cardiac lipid profile and nondipping blood
      pressure pattern during transition to diastolic dysfunction in male db/db mice.
AB  - Obesity and a nondipping circadian blood pressure (BP) pattern are associated
      with diastolic dysfunction. Ectopic lipid accumulation is increasingly recognized
      as an important metabolic abnormality contributing to diastolic dysfunction.
      However, little is known about the contribution of different lipids and the
      composition of lipid analytes to diastolic dysfunction. We have performed
      functional and structural studies and analyzed cardiac lipid profile at two time
      points during progression to diastolic dysfunction in a genetic model of obesity.
      Serial cardiac magnetic resonance imaging and telemetric measures of BP between
      12 and 15 wk of age in obese male db/db mice indicated a nondipping circadian BP
      pattern and normal diastolic function at 12 wk that progressed to a deteriorating
      nondipping pattern and onset of diastolic dysfunction at 15 wk of age. Lipidomic
      analysis demonstrated elevated fatty acids and ceramides in db/db at 12 wk, but
      their levels were decreased at 15 wk, and this was accompanied by persistent
      mitochondrial ultrastructural abnormalities in concert with evidence of increased
      fatty acid oxidation and enhanced production of reactive oxygen species.
      Triacylglyceride and diacylglyceride levels were elevated at both 12 and 15 wk,
      but their composition changed to consist of more saturated and less unsaturated
      fatty acyl at 15 wk. An increase in the lipid droplets was apparent at both time
      points, and this was associated with increases in phosphatidycholine. In
      conclusion, a distinct pattern of myocardial lipid remodeling, accompanied by
      oxidative stress, is associated with the onset of diastolic dysfunction in obese,
      insulin-resistant db/db mice.

PMID- 23142809
TI  - Glucocorticoids enhance CD163 expression in placental Hofbauer cells.
AB  - Periplacental levels of glucocorticoid (GC) peak at parturition, and synthetic GC
      is administered to women at risk for preterm delivery. However, little is known
      concerning cell-type-specific effects of GC in placenta. Hofbauer cells (HBCs)
      are fetal macrophages that are located adjacent to fetal capillaries in placenta.
      The goal of the current study was to determine whether GC treatment altered HBC
      gene expression and function. Western blotting and flow cytometry revealed CD163
      and folate receptor-beta (FR-beta), markers of antiinflammatory M2 macrophages,
      were specifically expressed by primary cultures of HBCs immunopurified from human
      term placentas. GC receptor mRNA and protein levels were higher in HBCs compared
      with placental fibroblasts. Treatment of HBCs with cortisol or dexamethasone
      (DEX) markedly and specifically enhanced CD163 protein and mRNA levels, whereas
      expression of FR-beta and CD68 were largely unresponsive to GC treatment. DEX
      treatment also increased hemoglobin uptake by HBCs, evidence of enhanced HBC
      function. The level of CD163 mRNA, but not FR-beta or CD68 mRNA, was stimulated
      in placental explant cultures by DEX treatment, and increased CD163/FR-beta and
      CD163/CD68 mRNA ratios sensitively reflected the response to GC. Maternal GC
      administration was associated with increased CD163/FR-beta and CD163/CD68 mRNA
      ratios in placentas from women with spontaneous preterm birth. In conclusion, in
      vitro studies indicated that GC treatment specifically up-regulated CD163
      expression in HBCs and enhanced HBC function. In addition, the observed
      alterations in patterns of expression of macrophage marker genes associated with
      maternal GC administration suggest that HBCs are in vivo targets of GC action.

PMID- 23142811
TI  - Deiodinase activities in thyroids and tissues of iodine-deficient female rats.
AB  - Severe iodine deficiency is characterized by goiter, preferential synthesis, and
      secretion of T(3) in thyroids, hypothyroxinemia in plasma and tissues, normal or
      low plasma T(3), and slightly increased plasma TSH. We studied changes in
      deiodinase activities and mRNA in several tissues of rats maintained on low
      iodine diets (LIDs) or LIDs supplemented with iodine (LID+I). T(4) and T(3)
      concentrations decreased in plasma, tissues, and thyroids of LID rats, and T(4)
      decreased more than T(3) (50%). The highest type 1 iodothyronine deiodinase (D1)
      activities were found in the thyroid, kidney, and the liver; pituitary, lung, and
      ovary had lower D1 activities; but the lowest levels were found in the heart and
      skeletal muscle. D1 activity decreased in all tissues of LID rats (10-40% of
      LID+I rats), except for ovary and thyroids, which D1 activity increased 2.5-fold.
      Maximal type 2 iodothyronine deiodinase (D2) activities were found in thyroid,
      brown adipose tissue, and pituitary, increasing 6.5-fold in thyroids of LID rats
      and about 20-fold in the whole gland. D2 always increased in response to LID, and
      maximal increases were found in the cerebral cortex (19-fold), thyroid, brown
      adipose tissue, and pituitary (6-fold). Lower D2 activities were found in the
      ovary, heart, and adrenal gland, which increased in LID. Type 3 iodothyronine
      deiodinase activity was undetectable. Thyroidal Dio1 and Dio2 mRNA increased in
      the LID rats, and Dio1 decreased in the lung, with no changes in mRNA expression
      in other tissues. Our data indicate that LID induces changes in deiodinase
      activities, especially in the thyroid, to counteract the low T(4) synthesis and
      secretion, contributing to maintain the local T(3) concentrations in the tissues
      with D2 activity.

PMID- 23142812
TI  - Biomechanical performance of different cable and wire cerclage configurations.
AB  - PURPOSE: Cerclage technology is regaining interest due to the increasing number
      of periprosthetic fractures. Different wiring techniques have been formerly
      proposed and have hibernated over years. Hereby, they are compared to current
      cerclage technology. METHODS: Seven groups (n = 6) of different cable cerclage
      (O1.7 mm, crimp closure) configurations (one single cerclage looped once around
      the shells, one single cerclage looped twice, two cerclages each looped once) and
      solid wire cerclages (O1.5 mm, twist closure) (same configurations as cable
      cerclages, and two braided wires, twisted around each other looped once) fixed
      two cortical half shells of human femoral shaft mounted on a testing jig.
      Sinusoidal cyclic loading with constantly increasing force (0.1 N/cycle) was
      applied starting at 50 N peak load. Cerclage pretension (P), load leading to
      onset of plastic deformation (D) and load at total failure (T) were identified.
      Statistical differences between the groups were detected by univariate ANOVA.
      RESULTS: Double looped cables (P442N +/- 129; D1334N +/- 319; T2734N +/- 330)
      performed significantly better (p < 0.05) than single looped cables (P292N +/-
      56; D646N +/- 108; T1622N +/- 171) and were comparable to two single cables
      (P392N +/- 154; D1191N +/- 334; T2675N +/- 361). Double looped wires (P335N +/-
      49; D752N +/- 119; T1359N +/- 80) were significantly better (p < 0.05) than
      single looped wires (P181N +/- 16; D343N +/- 33; T606N +/- 109) and performed
      similarly to single looped cables. Braided wires (P119N +/- 26; D225N +/- 55;
      T919N +/- 197) exhibited early loss of pretension and plastic deformation.
      CONCLUSION: Double looped cerclages provided a better fixation stability compared
      to a single looped cerclage. Double looped wires were comparable to a single
      looped cable. The use of braided wires could not be recommended mechanically.

PMID- 23142810
TI  - WNT4 acts downstream of BMP2 and functions via beta-catenin signaling pathway to
      regulate human endometrial stromal cell differentiation.
AB  - Differentiation of endometrial stromal cells into decidual cells is a
      prerequisite for successful embryo implantation. Our previous studies in the
      mouse have shown that bone morphogenetic protein 2 (BMP2), a morphogen belonging
      to the TGFbeta superfamily, is essential for this differentiation process. BMP2
      is markedly induced in human primary endometrial stromal cells (HESCs) as they
      undergo differentiation in response to steroid hormones and cAMP. The present
      study was undertaken to identify the BMP2-mediated molecular pathways in primary
      cultures of HESCs during decidualization. Using gene expression profiling, we
      identified wingless-related murine mammary tumor virus integration site 4 (WNT4)
      as a target of BMP2 regulation during decidualization. Attenuation of WNT4
      expression in HESCs by small interfering RNA administration greatly reduced BMP2
      induced stromal differentiation. Additionally, adenovirus-mediated overexpression
      of WNT4 in HESCs markedly advanced the differentiation program, indicating that
      it is a key regulator of decidualization. The stimulatory effect of WNT4 was
      accompanied by the accumulation of active beta-catenin in the nuclei of
      decidualizing stromal cells, indicating the involvement of the canonical WNT
      signaling pathway. Functional inhibition of WNT4/beta-catenin pathway by Dickkopf
      1, an inhibitor of the canonical WNT signaling, or small interfering RNA-mediated
      silencing of beta-catenin expression, greatly reduced the BMP2- and WNT4-induced
      decidualization. Gene expression profiling revealed that Forkhead box protein O1,
      a forkhead family transcription factor and previously reported regulator of HESC
      differentiation, is a common downstream mediator of both BMP2 and WNT4 signaling.
      Taken together, these studies uncovered a linear pathway involving BMP2,
      WNT4/beta-catenin, and Forkhead box protein O1 that operates in human endometrium
      to critically control decidualization.

PMID- 23142813
TI  - Remission of anosognosia for right hemiplegia and neglect after caloric
      vestibular stimulation.
AB  - Neglect and related phenomena, as anosognosia for hemiplegia and
      somatoparaphrenia, are often associated to right-hemisphere lesions. These
      deficits can be alleviated by caloric vestibular stimulation, but little is known
      about the efficacy of this physiological intervention on neglect following left
      hemisphere lesions. Here we report the case of an ambidextrous left brain-damaged
      patient with severe right personal and extrapersonal neglect, anosognosia for
      right hemiplegia and somatoparaphrenia. These symptoms co-occurred with more
      typical manifestations of left-brain damage, such as aphasia and apraxia.
      Neurological examination revealed right hemiplegia, hemianesthesia and
      hemianopia. Visuo-spatial tests for personal and extrapersonal neglect, as well
      as an anosognosia questionnaire, were submitted before and after caloric
      vestibular stimulation. Results showed a dramatic improvement of anosognosia for
      hemiplegia and neglect; no change was observed for the remaining deficits. The
      results confirm the notion of the selectivity of vestibular stimulation for
      neglect and related disorders and extend this notion by showing that similar
      effects can be obtained after lesion of the left hemisphere, suggesting that
      similar mechanisms are responsible for left- and right-sided neglect. Such a
      peculiar association of language and visuo-spatial disorders jointly present
      after a left-sided lesion opens the question of the link between handedness and
      lateralization of cognitive functions.

PMID- 23142815
TI  - Differential involvement of the left frontal and temporal regions in verb naming:
      a tDCS treatment study.
AB  - PURPOSE: In aphasic patients, some studies have already emphasized the efficacy
      of transcranial direct current stimulation (tDCS) during the treatment of noun
      retrieval deficits. To date, in the same population, there are have been no
      studies addressing tDCS effects in the recovery of verb retrieval deficits. In
      this study, we wanted to test the potential of tDCS to improve verb production in
      a group of aphasic patients. METHODS: Seven chronic subjects participated in an
      intensive language training for their difficulties in action naming. Each subject
      was treated with tDCS (20 min., 1 mA) over the left hemisphere in three different
      conditions: anodic tDCS over Wernicke's area, anodic tDCS and sham stimulation
      over Broca's area. Each experimental condition was performed in five consecutive
      daily sessions over three weeks with 6 days of intersession interval. RESULTS: In
      all patients, results showed a significantly better response accuracy during the
      anodic tDCS over Broca's area with respect to the other two conditions which
      still persisted at one month after the end of the treatment suggesting a long
      term effect on the recovery of their verb retrieval deficits. CONCLUSION: These
      findings further confirm that tDCS represents a useful new therapeutic
      interventions for the rehabilitation of lexical deficits in aphasic patients.

PMID- 23142814
TI  - Effects of motor skill learning on reciprocal inhibition.
AB  - PURPOSE: Learning a skilled movement is associated with more efficient use of
      subcortical motor circuits which can coordinate features of the movements such as
      the timing and patterns of activation of different muscles. Learning a motor
      skill could strengthen spinal interneuron circuits that facilitate the movement.
      We hypothesized that learning a simple, alternating movement would produce
      changes in spinal circuits that mediate reciprocal inhibition between antagonist
      muscles. METHODS: Sixteen healthy adult subjects were trained to perform a wrist
      flexion and extension task to control the movement of a cursor between targets
      appearing on a computer display. The goal of the task was to hit the targets.
      Subjects practiced for 15 minutes daily until reaching the acquisition criterion.
      Surface EMG recordings from wrist flexor and extensor muscles showed reduced co
      contraction during acquisition of the task. RESULTS: Compared to the initial
      session, in the final session short-latency reciprocal inhibition was enhanced
      during the late-extension phase in the final session. This phase-dependent
      increase in short-latency reciprocal inhibition is likely to facilitate switching
      activation between wrist antagonistic muscles. CONCLUSIONS: Learning a motor
      skill can produce alterations in spinal reflex circuits that facilitate the
      desired movement.

PMID- 23142816
TI  - Behavioral and neural evidence of increased attention to the bottom half of the
      face in deaf signers.
AB  - PURPOSE: This study examined the effects of deafness and sign language use on the
      distribution of attention across the top and bottom halves of faces. METHODS: In
      a composite face task, congenitally deaf signers and typically hearing controls
      made same/different judgments of the top or bottom halves of faces presented with
      the halves aligned or spatially misaligned, while event-related potentials (ERPs)
      were recorded. RESULTS: Both groups were more accurate when judging misaligned
      than aligned faces, which indicates holistic face processing. Misalignment
      affected all ERP components examined, with effects on the N170 resembling those
      of face inversion. Hearing adults were similarly accurate when judging the top
      and bottom halves of the faces, but deaf signers were more accurate when
      attending to the bottom than the top. Attending to the top elicited faster P1 and
      N170 latencies for both groups; within the deaf group, this effect was greatest
      for individuals who produced the highest accuracies when attending to the top.
      CONCLUSIONS: These findings dovetail with previous research by providing
      behavioral and neural evidence of increased attention to the bottom half of the
      face in deaf signers, and by documenting that these effects generalize to a
      speeded task, in the absence of gaze shifts, with neutral facial expressions.

PMID- 23142817
TI  - Modulation by the noble gas argon of the catalytic and thrombolytic efficiency of
      tissue plasminogen activator.
AB  - Argon has been shown to provide cortical as well as, under certain conditions,
      subcortical neuroprotection in all models so far (middle cerebral artery
      occlusion, trauma, neonatal asphyxia, etc.). This has led to the suggestion that
      argon could be a cost-efficient alternative to xenon, a metabolically inert gas
      thought to be gold standard in gas pharmacology but whose clinical development
      suffers its little availability and excessive cost of production. However,
      whether argon interacts with the thrombolytic agent tissue plasminogen activator,
      which is the only approved therapy of acute ischemic stroke to date, still
      remains unknown. This latter point is not trivial since previous data have
      clearly demonstrated the inhibiting effect of xenon on tPA enzymatic and
      thrombolytic efficiency and the critical importance of the time at which xenon is
      administered, during or after ischemia, in order not to block thrombolysis and to
      obtain neuroprotection. Here, we investigated the effect of argon on tPA
      enzymatic and thrombolytic efficiency using in vitro methods shown to provide
      reliable prediction of the in vivo effects of both oxygen and the noble inert
      gases on tPA-induced thrombolysis. We found that argon has a concentration
      dependent dual effect on tPA enzymatic and thrombolytic efficiency. Low and high
      concentrations of argon of 25 and 75 vol% respectively block and increase tPA
      enzymatic and thrombolytic efficiency. The possible use of argon at low and high
      concentrations in the treatment of acute ischemic stroke if given during ischemia
      or after tPA-induced reperfusion is discussed as regards to its neuroprotectant
      action and its inhibiting and facilitating effects on tPA-induced thrombolysis.
      The mechanisms of argon-tPA interactions are also discussed.

PMID- 23142818
TI  - Protein typing of circulating microvesicles allows real-time monitoring of
      glioblastoma therapy.
AB  - Glioblastomas shed large quantities of small, membrane-bound microvesicles into
      the circulation. Although these hold promise as potential biomarkers of
      therapeutic response, their identification and quantification remain challenging.
      Here, we describe a highly sensitive and rapid analytical technique for profiling
      circulating microvesicles directly from blood samples of patients with
      glioblastoma. Microvesicles, introduced onto a dedicated microfluidic chip, are
      labeled with target-specific magnetic nanoparticles and detected by a
      miniaturized nuclear magnetic resonance system. Compared with current methods,
      this integrated system has a much higher detection sensitivity and can
      differentiate glioblastoma multiforme (GBM) microvesicles from nontumor host cell
      derived microvesicles. We also show that circulating GBM microvesicles can be
      used to analyze primary tumor mutations and as a predictive metric of treatment
      induced changes. This platform could provide both an early indicator of drug
      efficacy and a potential molecular stratifier for human clinical trials.

PMID- 23142819
TI  - Obesity in mice with adipocyte-specific deletion of clock component Arntl.
AB  - Adipocytes store excess energy in the form of triglycerides and signal the levels
      of stored energy to the brain. Here we show that adipocyte-specific deletion of
      Arntl (also known as Bmal1), a gene encoding a core molecular clock component,
      results in obesity in mice with a shift in the diurnal rhythm of food intake, a
      result that is not seen when the gene is disrupted in hepatocytes or pancreatic
      islets. Changes in the expression of hypothalamic neuropeptides that regulate
      appetite are consistent with feedback from the adipocyte to the central nervous
      system to time feeding behavior. Ablation of the adipocyte clock is associated
      with a reduced number of polyunsaturated fatty acids in adipocyte triglycerides.
      This difference between mutant and wild-type mice is reflected in the circulating
      concentrations of polyunsaturated fatty acids and nonesterified polyunsaturated
      fatty acids in hypothalamic neurons that regulate food intake. Thus, this study
      reveals a role for the adipocyte clock in the temporal organization of energy
      regulation, highlights timing as a modulator of the adipocyte-hypothalamic axis
      and shows the impact of timing of food intake on body weight.

PMID- 23142820
TI  - Targeted estrogen delivery reverses the metabolic syndrome.
AB  - We report the development of a new combinatorial approach that allows for peptide
      mediated selective tissue targeting of nuclear hormone pharmacology while
      eliminating adverse effects in other tissues. Specifically, we report the
      development of a glucagon-like peptide-1 (GLP-1)-estrogen conjugate that has
      superior sex-independent efficacy over either of the individual hormones alone to
      correct obesity, hyperglycemia and dyslipidemia in mice. The therapeutic benefits
      are driven by pleiotropic dual hormone action to improve energy, glucose and
      lipid metabolism, as shown by loss-of-function models and genetic action
      profiling. Notably, the peptide-based targeting strategy also prevents hallmark
      side effects of estrogen in male and female mice, such as reproductive endocrine
      toxicity and oncogenicity. Collectively, selective activation of estrogen
      receptors in GLP-1-targeted tissues produces unprecedented efficacy to enhance
      the metabolic benefits of GLP-1 agonism. This example of targeting the metabolic
      syndrome represents the discovery of a new class of therapeutics that enables
      synergistic co-agonism through peptide-based selective delivery of small
      molecules. Although our observations with the GLP-1-estrogen conjugate justify
      translational studies for diabetes and obesity, the multitude of other possible
      combinations of peptides and small molecules may offer equal promise for other
      diseases.

PMID- 23142821
TI  - A live, impaired-fidelity coronavirus vaccine protects in an aged,
      immunocompromised mouse model of lethal disease.
AB  - Live, attenuated RNA virus vaccines are efficacious but subject to reversion to
      virulence. Among RNA viruses, replication fidelity is recognized as a key
      determinant of virulence and escape from antiviral therapy; increased fidelity is
      attenuating for some viruses. Coronavirus (CoV) replication fidelity is
      approximately 20-fold greater than that of other RNA viruses and is mediated by a
      3'->5' exonuclease (ExoN) activity that probably functions in RNA proofreading.
      In this study we demonstrate that engineered inactivation of severe acute
      respiratory syndrome (SARS)-CoV ExoN activity results in a stable mutator
      phenotype with profoundly decreased fidelity in vivo and attenuation of
      pathogenesis in young, aged and immunocompromised mice. The ExoN inactivation
      genotype and mutator phenotype are stable and do not revert to virulence, even
      after serial passage or long-term persistent infection in vivo. ExoN inactivation
      has potential for broad applications in the stable attenuation of CoVs and,
      perhaps, other RNA viruses.

PMID- 23142823
TI  - Cold tolerance abilities of two entomopathogenic nematodes, Steinernema feltiae
      and Heterorhabditis bacteriophora.
AB  - Entomopathogenic nematodes are effective biological control agents against insect
      pests but their commercial application is restricted by their limited shelf life.
      This study applies our knowledge of the cold tolerance of nematodes to this
      problem and investigates further the cold tolerance mechanisms of Steinernema
      feltiae and Heterorhabditis bacteriophora infective juveniles. When frozen using
      a fast freezing regime these nematodes are moderately freezing tolerant, with a
      lower lethal temperature of -5 degrees C. Survival is significantly enhanced by
      slow freezing overnight (at -1 degrees C), with a decrease in the lower lethal
      temperature to -14 degrees C. This may indicate that these nematodes are capable
      of cryoprotective dehydration. Acclimation at 5 degrees C further enhanced
      freezing survival in S. feltiae but only by a small amount. Nematodes that had
      survived freezing to -13 degrees C retained their pathogenicity to an insect
      host. Rapid cold hardening or exposure to a cold shock had no significant effect
      on freezing survival. The further development of methods based on cryoprotective
      dehydration may result in a method for the commercial storage of these nematodes.

PMID- 23142822
TI  - Maintenance of hematopoietic stem cells through regulation of Wnt and mTOR
      pathways.
AB  - Hematopoietic stem cell (HSC) self renewal and lineage commitment depend on
      complex interactions with the microenvironment. The ability to maintain or expand
      HSCs for clinical applications or basic research has been substantially limited
      because these interactions are not well defined. Recent evidence suggests that
      HSCs reside in a low-perfusion, reduced-nutrient niche and that nutrient-sensing
      pathways contribute to HSC homeostasis. Here we report that suppression of the
      mTOR pathway, an established nutrient sensor, combined with activation of
      canonical Wnt-beta-catenin signaling, allows for the ex vivo maintenance of human
      and mouse long-term HSCs under cytokine-free conditions. We also show that the
      combination of two clinically approved medications that together activate Wnt
      beta-catenin and inhibit mTOR signaling increases the number (but not the
      proportion) of long-term HSCs in vivo.

PMID- 23142824
TI  - Reduced Geminin levels promote cellular senescence.
AB  - Cellular senescence is a permanent out-of-cycle state regulated by molecular
      circuits acting during the G1 phase of the cell cycle. Cdt1 is a central
      regulator of DNA replication licensing acting during the G1 phase and it is
      negatively controlled by Geminin. Here, we characterize the cell cycle expression
      pattern of Cdt1 and Geminin during successive passages of primary fibroblasts and
      compare it to tumour-derived cell lines. Cdt1 and Geminin are strictly expressed
      in distinct subpopulations of young fibroblasts, similarly to cancer cells, with
      Geminin accumulating shortly after the onset of S phase. Cdt1 and Geminin are
      down-regulated when primary human and mouse fibroblasts undergo replicative or
      stress-induced senescence. RNAi-mediated Geminin knock-down in human cells
      enhances the appearance of phenotypic and molecular features of senescence. Mouse
      embryonic fibroblasts heterozygous for Geminin exhibit accelerated senescence
      compared to control fibroblasts. In contrast, ectopic expression of Geminin in
      mouse embryonic fibroblasts delays the appearance of the senescent phenotype.
      Taken together, our data suggest that changes in Geminin expression levels affect
      the establishment of senescence pathways.

PMID- 23142825
TI  - Perugia ileal neobladder: functional results and complications.
AB  - PURPOSE: To evaluate the long-term functional results and complications of an
      orthotopic ileal neobladder, defined as perugia ileal neobladder (PIN), in a
      group of patients with bladder cancer who underwent radical cystectomy (RC).
      METHODS: Between 1993 and 2009, 237 consecutive patients who underwent RC for non
      metastatic bladder cancer and orthotopic ileal neobladder reconstruction were
      enrolled. The neobladder was created using a modified Camey-II technique and
      consisted of a detubularized ileal loop of 45 cm using a vertical "Y" shape.
      Complications (<90 days) were reviewed and staged according to Clavien-Dindo
      classification and evaluated at long-term follow-up. Standard monitoring for
      cancer recurrence (computerized tomography, bone scan), cystourethrography,
      urodynamics and frequency/volume charts were performed during follow-up. RESULTS:
      The median follow-up was 64 months, and the 5-year overall survival rate was 64
      %. Early complications were mostly grade I and II; grade III and IV complications
      were observed in 27 patients. Perioperative mortality rate was 1.6 %. The most
      frequent late complications were neobladder-ureteral reflux, urolithiasis and
      urethral anastomotic stricture. Daytime and nighttime urinary continence were
      93.5 and 83.9 %, respectively. All patients were able to completely empty
      neobladders. Twenty patients were followed up for at least 10 years and presented
      satisfactory functional results. CONCLUSIONS: Surgical morbidity of RC and
      orthotopic neobladder was significant; however, the rate of grade III-IV
      complications was low. The long-term functional results of the PIN were
      interesting, confirming that appropriate patients' selection, adequate surgical
      technique, accurate patients' counseling and follow-up are essential.

PMID- 23142826
TI  - Batch to flow deoxygenation using visible light photoredox catalysis.
AB  - Herein we report a one-pot deoxygenation protocol for primary and secondary
      alcohols developed via the combination of the Garegg-Samuelsson reaction, visible
      light-photoredox catalysis, and flow chemistry. This procedure is characterized
      by mild reaction conditions, easy-to-handle reactants and reagents, excellent
      functional group tolerance, and good yields.

PMID- 23142827
TI  - Rapid fabrication and piezoelectric tuning of micro- and nanopores in single
      crystal quartz.
AB  - We outline the fabrication of piezoelectric through-pores in crystalline quartz
      using a rapid micromachining process, and demonstrate piezoelectric deformation
      of the pore. The single-step fabrication technique combines ultraviolet (UV)
      laser irradiation with a thin layer of absorbing liquid in contact with the UV
      transparent quartz chip. The effects of different liquid media are shown. We
      demonstrate that small exit pores, with diameters nearing the 193 nm laser
      wavelength and with a smooth periphery, can be achieved in 350 MUm thick quartz
      wafers. Special crater features centring on the exit pores are also fabricated,
      and the depth of these craters are tuned. Moreover, by applying a voltage bias
      across the thickness of this piezoelectric wafer, we controllably contract and
      expand the pore diameter. We also provide a sample application of this device by
      piezoelectrically actuating alamethicin ion channels suspended over the
      deformable pore.

PMID- 23142828
TI  - Software applications toward quantitative metabolic flux analysis and modeling.
AB  - Metabolites and their pathways are central for adaptation and survival. Metabolic
      modeling elucidates in silico all the possible flux pathways (flux balance
      analysis, FBA) and predicts the actual fluxes under a given situation, further
      refinement of these models is possible by including experimental isotopologue
      data. In this review, we initially introduce the key theoretical concepts and
      different analysis steps in the modeling process before comparing flux
      calculation and metabolite analysis programs such as C13, BioOpt, COBRA toolbox,
      Metatool, efmtool, FiatFlux, ReMatch, VANTED, iMAT and YANA. Their respective
      strengths and limitations are discussed and compared to alternative software.
      While data analysis of metabolites, calculation of metabolic fluxes, pathways and
      their condition-specific changes are all possible, we highlight the
      considerations that need to be taken into account before deciding on a specific
      software. Current challenges in the field include the computation of large-scale
      networks (in elementary mode analysis), regulatory interactions and detailed
      kinetics, and these are discussed in the light of powerful new approaches. 

PMID- 23142829
TI  - Motor deficits associated with changes in beta-amyloid in Parkinson's disease.

PMID- 23142830
TI  - Vestibular migraine: diagnostic criteria.
AB  - This paper presents diagnostic criteria for vestibular migraine, jointly
      formulated by the Committee for Classification of Vestibular Disorders of the
      Barany Society and the Migraine Classification Subcommittee of the International
      Headache Society (IHS). The classification includes vestibular migraine and
      probable vestibular migraine. Vestibular migraine will appear in an appendix of
      the third edition of the International Classification of Headache Disorders
      (ICHD) as a first step for new entities, in accordance with the usual IHS
      procedures. Probable vestibular migraine may be included in a later version of
      the ICHD, when further evidence has been accumulated. The diagnosis of vestibular
      migraine is based on recurrent vestibular symptoms, a history of migraine, a
      temporal association between vestibular symptoms and migraine symptoms and
      exclusion of other causes of vestibular symptoms. Symptoms that qualify for a
      diagnosis of vestibular migraine include various types of vertigo as well as head
      motion-induced dizziness with nausea. Symptoms must be of moderate or severe
      intensity. Duration of acute episodes is limited to a window of between 5 minutes
      and 72 hours.

PMID- 23142831
TI  - Subjective posture in tridimensional space.
AB  - The internal representation of the body is intimately related to postural
      orientation. This assists us to correctly identify our position relative to the
      earth-vertical. The postural orientation about the pitch-Y axis is by default
      forward tilted while there is no such default about the roll-X axis. We
      hypothetized that the internal representation of body position would be different
      between the Y and X axes. We designed a study to assess the accuracy of self
      driven whole-body orienting to the horizontal and the vertical about the X (roll)
      and Y (pitch) axes, with healthy seated subjects in complete darkness. Consistent
      with our hypothesis, the results showed that when trying to reach the horizontal
      with the X-axis, subjects remained on the same tilted direction as the initial
      posture. On the return way to the vertical, the subjects did not cross this
      (vertical) line. Whereas when reaching the horizontal with the Y-axis, there was
      an undershoot on the supine direction, and an overshoot on the prone direction:
      this discrepancy could be due to somatosensory cues to subjects in seated
      posture. The relevant mechanisms related to the internal representation of the
      body and graviceptive systems underlying the construction of an head-foot line
      are discussed.

PMID- 23142832
TI  - Measuring dynamics of the subjective vertical and tilt using a joystick.
AB  - Humans are able to estimate the vertical direction of an Earth fixed reference
      frame, which estimate is known as the subjective vertical (SV). To identify the
      SV, a distinction must be made between accelerations due to self-motion and
      gravity. Previous studies on this topic measured the SV using a variety of
      methods possibly affecting the outcome differently. In this study subjects were
      sinusoidally moved around their naso-occipital axis and their SV was dynamically
      measured using a joystick. In half the experimental conditions, the joystick was
      moved with the motion and was kept vertical on other experimental conditions,
      thus moving against self-motion. Although physically indicating the same angle,
      the average perceived angle was larger when moving the joystick with the motion
      than against. The difference can be explained by assuming an idiotropic vector
      being at issue when measuring the subjective vertical, and not when measuring
      subjective tilt.

PMID- 23142833
TI  - Posturography and locomotor tests of dynamic balance after long-duration
      spaceflight.
AB  - The currently approved objective clinical measure of standing balance in
      astronauts after space flight is the Sensory Organization Test battery of
      computerized dynamic posturography. No tests of walking balance are currently
      approved for standard clinical testing of astronauts. This study determined the
      sensitivity and specificity of standing and walking balance tests for astronauts
      before and after long-duration space flight. Astronauts were tested on an
      obstacle avoidance test known as the Functional Mobility Test (FMT) and on the
      Sensory Organization Test using sway-referenced support surface motion with eyes
      closed (SOT 5) before and six months after (n=15) space flight on the
      International Space Station. They were tested two to seven days after landing.
      Scores on SOT tests decreased and scores on FMT increased significantly from pre-
      to post-flight. In other words, post-flight scores were worse than pre-flight
      scores. SOT and FMT scores were not significantly related. ROC analyses indicated
      supra-clinical cut-points for SOT 5 and for FMT. The standard clinical cut-point
      for SOT 5 had low sensitivity to post-flight astronauts. Higher cut-points
      increased sensitivity to post-flight astronauts but decreased specificity to pre
      flight astronauts. Using an FMT cut-point that was moderately highly sensitive
      and highly specific plus SOT 5 at the standard clinical cut-point was no more
      sensitive than SOT 5, alone. FMT plus SOT 5 at higher cut-points was more
      specific and more sensitive. The total correctly classified was highest for FMT,
      alone, and for FMT plus SOT 5 at the highest cut-point. These findings indicate
      that standard clinical comparisons are not useful for identifying problems.
      Testing both standing and walking balance will be more likely to identify balance
      deficits.

PMID- 23142834
TI  - Benign paroxysmal positional vertigo and head position during sleep.
AB  - To determine whether any particular head positions during sleep are associated
      with BPPV, head position during sleep was monitored for 3 days in 50 BPPV
      patients after the disappearance of positional nystagmus and in 25 normal control
      subjects. A gravity sensor was attached to the center of the subject's forehead
      at home. The positional angle of the head was measured at 5-second intervals
      during sleep. In BPPV, the posterior semicircular canal was involved in 40
      patients and the lateral semicircular canal in 10 patients. Recurrence was found
      in 22 of 50 BPPV patients. BPPV patients with recurrence were significantly more
      likely to sleep in the affected-ear-down 45-degree head position than were
      patients with no history of recurrence (P< 0.02). When the head is in the
      affected-ear-down 45-degree head position, the non-ampullated half of the
      posterior semicircular canal and the non-ampullated half of the lateral
      semicircular canal are nearly in the earth-vertical position, making it easier
      for detached otoconia to fall into the posterior or lateral semicircular canal
      and to agglomerate and attain a certain size in the lowest portion of each
      semicircular canal. Our findings showed that the affected-ear-down 45-degree head
      position during sleep could be an etiological factor of BPPV, more particularly
      in patients with recurrent BPPV.

PMID- 23142835
TI  - Subjective visual vertical perception in patients with vestibular neuritis and
      sudden sensorineural hearing loss.
AB  - OBJECTIVE: To determine the subjective visual vertical (SVV) perception in
      patients with vestibular neuritis (VN) and sudden sensorineural hearing loss
      (SSHL) using the SVV test and other neuro-otological examinations, namely, the
      vestibular evoked myogenic potential (VEMP) and caloric tests, and to clarify
      which vestibular nerve function is associated with an SVV shift. PATIENTS AND
      METHODS: We performed the SVV test in 36 VN patients and 80 SSHL patients.
      Thereafter, we investigated directional changes in the SVV in the VN and SSHL
      patients, and compared the results of the SVV test with those of the VEMP and
      caloric tests. RESULTS: Abnormal SVV (> 2 degrees  was found at a rate of 69.4%
      in the VN patients and 26.3% in the SSHL patients. In all except 1 VN patient,
      the SVV tilted to the lesion side. The rate of abnormal SVV was significantly
      higher in patients with complete canal paresis (CP) than in patients with partial
      CP. There was no significant relationship between the rates of abnormal SVV and
      VEMP. In the SSHL patients, neither the SVV nor the VEMP affected the hearing
      outcome and patients with abnormal VEMP tended to show abnormal SVV. CONCLUSION:
      VN patients showed a higher rate of abnormal SVV than SSHL patients. From the
      results, it is speculated that the superior vestibular nerve function mainly
      affects the SVV tilt, although the inferior vestibular nerve function may also
      have an effect.

PMID- 23142836
TI  - Resonant light trapping in ultrathin films for water splitting.
AB  - Semiconductor photoelectrodes for solar hydrogen production by water
      photoelectrolysis must employ stable, non-toxic, abundant and inexpensive visible
      light absorbers. Iron oxide (alpha-Fe(2)O(3)) is one of few materials meeting
      these requirements, but its poor transport properties present challenges for
      efficient charge-carrier generation, separation, collection and injection. Here
      we show that these challenges can be addressed by means of resonant light
      trapping in ultrathin films designed as optical cavities. Interference between
      forward- and backward-propagating waves enhances the light absorption in quarter
      wave or, in some cases, deeper subwavelength films, amplifying the intensity
      close to the surface wherein photogenerated minority charge carriers (holes) can
      reach the surface and oxidize water before recombination takes place. Combining
      this effect with photon retrapping schemes, such as using V-shaped cells,
      provides efficient light harvesting in ultrathin films of high internal quantum
      efficiency, overcoming the trade-off between light absorption and charge
      collection. A water photo-oxidation current density of 4 mA cm(-2) was achieved
      using a V-shaped cell comprising ~26-nm-thick Ti-doped alpha-Fe(2)O(3) films on
      back-reflector substrates coated with silver-gold alloy.

PMID- 23142837
TI  - Tailored exciton diffusion in organic photovoltaic cells for enhanced power
      conversion efficiency.
AB  - Photoconversion in planar-heterojunction organic photovoltaic cells (OPVs) is
      limited by a short exciton diffusion length (L(D)) that restricts migration to
      the dissociating electron donor/acceptor interface. Consequently, bulk
      heterojunctions are often used to realize high efficiency as these structures
      reduce the distance an exciton must travel to be dissociated. Here, we present an
      alternative approach that seeks to directly engineer L(D) by optimizing the
      intermolecular separation and consequently, the photophysical parameters
      responsible for excitonic energy transfer. By diluting the electron donor boron
      subphthalocyanine chloride into a wide-energy-gap host material, we optimize the
      degree of interaction between donor molecules and observe a ~50% increase in
      L(D). Using this approach, we construct planar-heterojunction OPVs with a power
      conversion efficiency of (4.4 +/- 0.3)%, > 30% larger than the case of optimized
      devices containing an undiluted donor layer. The underlying correlation between
      L(D) and the degree of molecular interaction has wide implications for the design
      of both OPV active materials and device architectures.

PMID- 23142838
TI  - Mesostructured thin films as electrocatalysts with tunable composition and
      surface morphology.
AB  - Among the most challenging issues in technologies for electrochemical energy
      conversion are the insufficient activity of the catalysts for the oxygen
      reduction reaction, catalyst degradation and carbon-support corrosion. In an
      effort to address these barriers, we aimed towards carbon-free multi/bimetallic
      materials in the form of mesostructured thin films with tailored physical
      properties. We present here a new class of metallic materials with tunable near
      surface composition, morphology and structure that have led to greatly improved
      affinity for the electrochemical reduction of oxygen. The level of activity for
      the oxygen reduction reaction established on mesostructured thin-film catalysts
      exceeds the highest value reported for bulk polycrystalline Pt bimetallic alloys,
      and is 20-fold more active than the present state-of-the-art Pt/C nanoscale
      catalyst.

PMID- 23142839
TI  - Ultrasmall implantable composite microelectrodes with bioactive surfaces for
      chronic neural interfaces.
AB  - Implantable neural microelectrodes that can record extracellular biopotentials
      from small, targeted groups of neurons are critical for neuroscience research and
      emerging clinical applications including brain-controlled prosthetic devices. The
      crucial material-dependent problem is developing microelectrodes that record
      neural activity from the same neurons for years with high fidelity and
      reliability. Here, we report the development of an integrated composite electrode
      consisting of a carbon-fibre core, a poly(p-xylylene)-based thin-film coating
      that acts as a dielectric barrier and that is functionalized to control intrinsic
      biological processes, and a poly(thiophene)-based recording pad. The resulting
      implants are an order of magnitude smaller than traditional recording electrodes,
      and more mechanically compliant with brain tissue. They were found to elicit much
      reduced chronic reactive tissue responses and enabled single-neuron recording in
      acute and early chronic experiments in rats. This technology, taking advantage of
      new composites, makes possible highly selective and stealthy neural interface
      devices towards realizing long-lasting implants.

PMID- 23142840
TI  - A full-parameter unidirectional metamaterial cloak for microwaves.
AB  - Invisibility is a notion that has long captivated the popular imagination.
      However, in 2006, invisibility became a practical matter for the scientific
      community as well, with the suggestion that artificially structured metamaterials
      could enable a new electromagnetic design paradigm, now termed transformation
      optics. Since the advent of transformation optics and subsequent initial
      demonstration of the microwave cloak, the field has grown rapidly. However, the
      complexity of the transformation optics material prescription has continually
      forced researchers to make simplifying approximations to achieve even a subset of
      the desired functionality. These approximations place profound limitations on the
      performance of transformation optics devices in general, and cloaks especially.
      Here, we design and experimentally characterize a two-dimensional, unidirectional
      cloak that makes no approximations to the underlying transformation optics
      formulation, yet is capable of reducing the scattering of an object ten
      wavelengths in size. We demonstrate that this approximation-free design regains
      the performance characteristics promised by transformation optics.

PMID- 23142841
TI  - Towards stable catalysts by controlling collective properties of supported metal
      nanoparticles.
AB  - Supported metal nanoparticles play a pivotal role in areas such as
      nanoelectronics, energy storage/conversion and as catalysts for the sustainable
      production of fuels and chemicals. However, the tendency of nanoparticles to grow
      into larger crystallites is an impediment for stable performance. Exemplarily,
      loss of active surface area by metal particle growth is a major cause of
      deactivation for supported catalysts. In specific cases particle growth might be
      mitigated by tuning the properties of individual nanoparticles, such as size,
      composition and interaction with the support. Here we present an alternative
      strategy based on control over collective properties, revealing the pronounced
      impact of the three-dimensional nanospatial distribution of metal particles on
      catalyst stability. We employ silica-supported copper nanoparticles as catalysts
      for methanol synthesis as a showcase. Achieving near-maximum interparticle
      spacings, as accessed quantitatively by electron tomography, slows down
      deactivation up to an order of magnitude compared with a catalyst with a non
      uniform nanoparticle distribution, or a reference Cu/ZnO/Al(2)O(3) catalyst. Our
      approach paves the way towards the rational design of practically relevant
      catalysts and other nanomaterials with enhanced stability and functionality, for
      applications such as sensors, gas storage, batteries and solar fuel production.

PMID- 23142842
TI  - P2-Na(x)VO2 system as electrodes for batteries and electron-correlated materials.
AB  - Layered oxides are the subject of intense studies either for their properties as
      electrode materials for high-energy batteries or for their original physical
      properties due to the strong electronic correlations resulting from their unique
      structure. Here we present the detailed phase diagram of the layered P2
      Na(x)VO(2) system determined from electrochemical intercalation/deintercalation
      in sodium batteries and in situ X-ray diffraction experiments. It shows that four
      main single-phase domains exist within the 0.5<=x<=0.9 range. During the sodium
      deintercalation (intercalation), they differ from one another in the
      sodium/vacancy ordering between the VO(2) slabs, which leads to commensurable or
      incommensurable superstructures. The electrochemical curve reveals that three
      peculiar compositions exhibit special structures for x  =  1/2, 5/8 and 2/3. The
      detailed structural characterization of the P2-Na(1/2)VO(2) phase shows that the
      Na(+) ions are perfectly ordered to minimize Na(+)/Na(+) electrostatic
      repulsions. Within the VO(2) layers, the vanadium ions form pseudo-trimers with
      very short V-V distances (two at 2.581 A and one at 2.687 A). This original
      distribution leads to a peculiar magnetic behaviour with a low magnetic
      susceptibility and an unexpected low Curie constant. This phase also presents a
      first-order structural transition above room temperature accompanied by magnetic
      and electronic transitions. This work opens up a new research domain in the field
      of strongly electron-correlated materials. From the electrochemical point of view
      this system may be at the origin of an entire material family optimized by
      cationic substitutions.

PMID- 23142843
TI  - Atomic mechanism and prediction of hydrogen embrittlement in iron.
AB  - Hydrogen embrittlement in metals has posed a serious obstacle to designing strong
      and reliable structural materials for many decades, and predictive physical
      mechanisms still do not exist. Here, a new H embrittlement mechanism operating at
      the atomic scale in alpha-iron is demonstrated. Direct molecular dynamics
      simulations reveal a ductile-to-brittle transition caused by the suppression of
      dislocation emission at the crack tip due to aggregation of H, which then permits
      brittle-cleavage failure followed by slow crack growth. The atomistic
      embrittlement mechanism is then connected to material states and loading
      conditions through a kinetic model for H delivery to the crack-tip region.
      Parameter-free predictions of embrittlement thresholds in Fe-based steels over a
      range of H concentrations, mechanical loading rates and H diffusion rates are
      found to be in excellent agreement with experiments. This work provides a
      mechanistic, predictive framework for interpreting experiments, designing
      structural components and guiding the design of embrittlement-resistant
      materials.

PMID- 23142845
TI  - Relationship between extreme pathways and structurally minimal pathways.
AB  - The determination of reaction pathways is one of the most important functions
      that should be performed in exploring the kinetics of catalyzed chemical
      reactions or biochemical reactions, the latter being generally catalyzed by
      enzymes. It is proven that the terms, "type-I extreme pathway" and "structurally
      minimal pathway", both introduced to characterize the kinetics of a catalyzed
      reaction are equivalent. These two terms are based on two distinct methodologies,
      one mainly rooted in convex analysis and the other in graph theory. The
      equivalence promises further even more effective methods for reaction-pathway
      identification by synergistic integration of existing ones. 

PMID- 23142844
TI  - Anesthetics interacting with lipid rafts.
AB  - The exact mechanism by which anesthetics induce cell membrane-mediated
      modifications is still an open question. Although the fluidization effect of the
      anesthetic molecules on the cellular membrane is widely recognized, it is not
      known if anesthetics show any preference for specific membrane domains, namely
      the lipid rafts. The importance of these membrane micro-domains derives from the
      fact that they have been associated with cell signaling pathways, as well as with
      specific drug interactions. The objective of this work is to contribute for the
      elucidation of this question through the comparison of the anesthetic
      interactions with membranes of various lipid compositions. Liposomes prepared
      with an equimolar mixture of POPC, sphingomyelin and cholesterol, were chosen as
      models for lipid rafts. The interactions of these liposomes with two local
      anesthetics, tetracaine and lidocaine, and one general anesthetic, propofol, were
      studied. The effect of cholesterol was investigated by comparing anesthetic
      interactions with POPC/SM liposomes and POPC/SM/CHOL liposomes. The following
      experimental techniques were used: quartz crystal microbalance with dissipation,
      differential scanning calorimetry and phosphorus nuclear magnetic resonance.
      Although the liposomes investigated by the different techniques are not in the
      same conditions, it is possible to assemble the information obtained from all
      experimental techniques employed to reach a general conclusion. Tetracaine
      interacts more with raftlike domains, lidocaine induces stronger modifications on
      POPC/SM liposomes and the results for propofol are not fully conclusive but it
      seems to be the least prone to lipid interactions. The results were compared with
      those obtained with DMPC-containing liposomes, reported in a previous work.

PMID- 23142846
TI  - Hydrodynamic characteristics and overall volumetric oxygen transfer coefficient
      of a new multi-environment bioreactor.
AB  - The hydrodynamic characteristics and the overall volumetric oxygen transfer
      coefficient of a new multi-environment bioreactor which is an integrated part of
      a wastewater treatment system, called BioCAST, were studied. This bioreactor
      contains several zones with different environmental conditions including aerobic,
      microaerophilic and anoxic, designed to increase the contaminant removal capacity
      of the treatment system. The multi-environment bioreactor is designed based on
      the concept of airlift reactors where liquid is circulated through the zones with
      different environmental conditions. The presence of openings between the aerobic
      zone and the adjacent oxygen-depleted microaerophilic zone changes the
      hydrodynamic properties of this bioreactor compared to the conventional airlift
      designs. The impact of operating and process parameters, notably the hydraulic
      retention time (HRT) and superficial gas velocity (U(G)), on the hydrodynamics
      and mass transfer characteristics of the system was examined. The results showed
      that liquid circulation velocity (V(L)), gas holdup (epsilon) and overall
      volumetric oxygen transfer coefficient (k(L)a(L)) increase with the increase of
      superficial gas velocity (U(G)), while the mean circulation time (t(c)) decreases
      with the increase of superficial gas velocity. The mean circulation time between
      the aerobic zone (riser) and microaerophilic zone (downcomer) is a stronger
      function of the superficial gas velocity for the smaller openings (1/2 in.)
      between the two zones, while for the larger opening (1 in.) the mean circulation
      time is almost independent of U(G) for U(G) >= 0.023 m/s. The smaller openings
      between the two zones provide higher mass transfer coefficient and better zone
      generation which will contribute to improved performance of the system during
      treatment operations.

PMID- 23142847
TI  - Gliomatosis cerebelli, an infantile cerebellar neoplasm that exhibited diffuse
      infiltration without forming a mass.

PMID- 23142848
TI  - Nucleophilic fluorination of beta-ketoester derivatives with HBF4.
AB  - Treating readily available alpha-diazo-beta-ketoesters with HBF(4) results in
      nucleophilic fluorination by the usually inert and stable tetrafluoroborate
      anion. The resulting alpha-fluoro-beta-ketoesters are highly versatile synthetic
      intermediates, for example in the preparation of fluoro-heterocycles, as
      illustrated by the direct formation of fluoro-pyrimidines, -pyrazoles and 
      coumarins in a single step.

PMID- 23142849
TI  - Central mechanisms for force and motion--towards computational synthesis of human
      movement.
AB  - Anatomical, physiological and experimental research on the human body can be
      supplemented by computational synthesis of the human body for all movement:
      routine daily activities, sports, dancing, and artistic and exploratory
      involvements. The synthesis requires thorough knowledge about all subsystems of
      the human body and their interactions, and allows for integration of known
      knowledge in working modules. It also affords confirmation and/or verification of
      scientific hypotheses about workings of the central nervous system (CNS). A
      simple step in this direction is explored here for controlling the forces of
      constraint. It requires co-activation of agonist-antagonist musculature. The
      desired trajectories of motion and the force of contact have to be provided by
      the CNS. The spinal control involves projection onto a muscular subset that
      induces the force of contact. The projection of force in the sensory motor cortex
      is implemented via a well-defined neural population unit, and is executed in the
      spinal cord by a standard integral controller requiring input from tendon organs.
      The sensory motor cortex structure is extended to the case for directing motion
      via two neural population units with vision input and spindle efferents. Digital
      computer simulations show the feasibility of the system. The formulation is
      modular and can be extended to multi-link limbs, robot and humanoid systems with
      many pairs of actuators or muscles. It can be expanded to include reticular
      activating structures and learning.

PMID- 23142850
TI  - Interventional neuroradiology. Editorial.

PMID- 23142851
TI  - Poor electroneurography but excellent hand function 31 years after nerve repair
      in childhood.
AB  - Children, in contrast to adults, show an excellent clinical recovery after a
      peripheral nerve injury, which may be explained by better peripheral nerve
      regeneration and a superior plasticity in the young brain. Our aim was to study
      the long-term electrophysiological outcome after nerve repair in children and
      young adults and to compare it with the clinical outcome. Forty-four patients,
      injured at an age younger than 21 years, were assessed by electrophysiology
      (amplitude, conduction velocity and distal motor latency) at a median of 31 years
      after a complete median or ulnar nerve injury at the level of the forearm.
      Electrophysiological evaluation showed pathology in all parameters and in all
      patients, irrespective of age at injury. No significant differences were observed
      in the electrophysiological results between those injured in childhood, that is,
      before the age of 12 years, and those injured in adolescence, that is, between 12
      and 20 years of age. In contrast, the clinical nerve function was significantly
      better for those injured in childhood (87% of complete recovery, P=0.002)
      compared with those injured in adolescence. We conclude that the mechanism behind
      the superior clinical outcome in children is not located at the periphery, but is
      explained by cerebral plasticity.

PMID- 23142852
TI  - Variations in Physician Attitudes Regarding ADHD and Their Association With
      Prescribing Practices.
AB  - OBJECTIVE: The objective of this study was to test whether physicians' attitudes
      regarding the impact of ADHD on health-related quality of life (HRQL) explain
      differences in practices for prescribing psychostimulants in children. METHOD: In
      a cross-sectional survey, U.S.-based pediatricians and psychiatrists
      ("physicians") used the Paper-Standard Gamble--a widely used preference-based
      assessment of HRQL--to rate four vignettes describing ADHD health states of
      varying severity. Associations between standard gamble scores and questions about
      prescribing practices were analyzed using ordinal logistic regression. RESULTS:
      Surveys were mailed to 291 physicians; 127 (44%) returned complete forms. Lower
      standard gamble scores were associated with more emphasis on children's ADHD
      symptoms (p = .03) and less emphasis on parents' concerns about stimulant side
      effects (p = .03) when prescribing psychostimulants. CONCLUSION: Differences in
      physician perceptions of the severity of ADHD symptoms and in their emphasis on
      parental concerns about side effects may help explain variations in ADHD
      psychostimulant prescription patterns.

PMID- 23142853
TI  - Parent Ratings of ADHD Symptoms in Chinese Urban Schoolchildren: Assessment With
      the Chinese ADHD Rating Scale-IV: Home Version.
AB  - OBJECTIVE: The objective of this study was to assess the psychometric properties
      of the Chinese ADHD Rating Scale-IV (ADHD RS-IV): Home Version and to explore
      parent ratings of ADHD symptoms in a large sample of urban schoolchildren in
      China. METHOD: Parents of a representative sample of 1,616 schoolchildren (aged 6
      17) in 12 Chinese cities completed the ADHD RS-IV: Home Version. RESULTS: The
      Chinese ADHD RS-IV: Home Version demonstrated satisfactory internal consistency,
      test-retest reliability, parent-teacher correlation, discriminant validity, and
      convergent validity. Factor analysis revealed the DSM-IV two-factor model with
      "inattention" and "hyperactivity-impulsivity" dimensions, accounting for equal
      variances. Parent ratings revealed lower/similar scores for Chinese
      schoolchildren compared with the U.S. CONCLUSION: The ADHD RS-IV: Home Version is
      a reliable and valid ADHD rating scale in China. The factor structure is similar
      but not identical to the U.S. STUDY: Normative data reveal cultural differences
      in some aspects of the parent ratings of ADHD.

PMID- 23142854
TI  - Post-release substance abuse outcomes among HIV-infected jail detainees: results
      from a multisite study.
AB  - HIV-infected individuals with substance use disorders have a high prevalence of
      medical and psychiatric morbidities that complicate treatment. Incarceration
      further disrupts healthcare access and utilization. Without appropriate diagnosis
      and treatment, drug relapse upon release exceeds 85 %, which contributes to poor
      health outcomes. A prospective cohort of 1,032 HIV-infected jail detainees were
      surveyed in a ten-site demonstration project during incarceration and six-months
      post-release, in order to examine the effect of predisposing factors, enabling
      resources and need factors on their subsequent drug use. Homelessness, pre
      incarceration cocaine and opioid use, and high drug and alcohol severity were
      significantly associated with cocaine and opioid relapse. Substance abuse
      treatment, though poorly defined, did not influence post-release cocaine and
      opioid use. An approach that integrates multiple services, simultaneously using
      evidence-based substance abuse, psychiatric care, and social services is needed
      to improve healthcare outcomes for HIV-infected persons transitioning from jails
      to the community.

PMID- 23142855
TI  - Barriers to medication adherence in behaviorally and perinatally infected youth
      living with HIV.
AB  - The study explored barriers to antiretroviral medication adherence in perinatally
      and behaviorally HIV infected adolescents and young adults in a cross-sectional,
      multisite sample. The study included a subset of a convenience sample from a
      cross-sectional analysis. Participants were youth with HIV ages 12-24 who were
      prescribed HIV medication and reported missing medication in the past 7 days (n =
      484, 28.4 % of protocol sample). The top barriers were similar for perinatally
      and behaviorally infected youth, but perinatally infected youth reported
      significantly more barriers. Forgetting, not feeling like taking medication and
      not wanting to be reminded of HIV infection were the most common barriers
      reported. Number of barriers was significantly correlated with percent of doses
      missed, viral load, and psychological distress for perinatally infected youth and
      with doses missed, psychological distress, and substance use for behaviorally
      infected youth. Interventions to improve adherence to HIV medications should not
      only address forgetfulness and choosing not to take medications, but also
      consider route of infection.

PMID- 23142856
TI  - Mobile VCT: reaching men and young people in urban and rural South African pilot
      studies (NIMH Project Accept, HPTN 043).
AB  - Mounting evidence exists that mobile voluntary counselling and testing (VCT) is
      able to extend coverage to new localities and populations. We describe two
      feasibility and acceptability pilot studies conducted in rural and urban South
      Africa in preparation for the larger NIMH Project Accept HIV prevention trial. A
      total of 1,015 individuals participated in the pilot studies. Participants in
      rural Vulindlela were younger (median 22 years) compared to urban Soweto (p <
      0.001). Young people were more likely to be first time testers in both sites (p =
      0.01 in Vulindlela, p < 0.001 in Soweto), with significantly more men likely to
      be first time testers than women (p = 0.01 in Vulindlela, p < 0.001 in Soweto).
      User satisfaction with mobile VCT was extremely high in both sites. Our study
      shows that providing mobile, high-quality and easy to access services in a high
      prevalence context is a feasible way to engage youth, men and more rural
      populations in HIV counselling and testing.

PMID- 23142857
TI  - Peer-education intervention to reduce injection risk behaviors benefits high-risk
      young injection drug users: a latent transition analysis of the CIDUS 3/DUIT
      study.
AB  - We analyzed data from a large randomized HIV/HCV prevention intervention trial
      with young injection drug users (IDUs) conducted in five U.S. cities. The trial
      compared a peer education intervention (PEI) with a time-matched, attention
      control group. Applying categorical latent variable analysis (mixture modeling)
      to baseline injection risk behavior data, we identified four distinct classes of
      injection-related HIV/HCV risk: low risk, non-syringe equipment-sharing, moderate
      risk syringe-sharing, and high-risk syringe-sharing. The trial participation rate
      did not vary across classes. We conducted a latent transition analysis using
      trial baseline and 6-month follow-up data, to test the effect of the intervention
      on transitions to the low-risk class at follow-up. Adjusting for gender, age, and
      race/ethnicity, a significant intervention effect was found only for the high
      risk class. Young IDU who exhibited high-risk behavior at baseline were 90% more
      likely to be in the low-risk class at follow-up after the PEI intervention,
      compared to the control group.

PMID- 23142858
TI  - Rhizobium qilianshanense sp. nov., a novel species isolated from root nodule of
      Oxytropis ochrocephala Bunge in China.
AB  - During a study of the diversity and phylogeny of rhizobia isolated from root
      nodules of Oxytropis ochrocephala grown in the northwest of China, four strains
      were classified in the genus Rhizobium on the basis of their 16S rRNA gene
      sequences. These strains have identical 16S rRNA gene sequences, which showed a
      mean similarity of 94.4 % with the most closely related species, Rhizobium
      oryzae. Analysis of recA and glnA sequences showed that these strains have less
      than 88.1 and 88.7 % similarity with the defined species of Rhizobium,
      respectively. The genetic diversity revealed by ERIC-PCR fingerprinting indicated
      that the isolates correspond to different strains. Strain CCNWQLS01(T) contains Q
      10 as the predominant ubiquinone. The major fatty acids were identified as
      feature 8 (C18: 1omega7c and/or C18: 1omega6c; 67.2 %). Therefore, a novel
      species Rhizobium qilianshanense sp. nov. is proposed, and CCNWQLS01(T) (= ACCC
      05747(T) = JCM 18337(T)) is designated as the type strain.

PMID- 23142859
TI  - Roseomonas musae sp. nov., a new bacterium isolated from a banana phyllosphere.
AB  - A Gram-negative, coccobacilli, non-spore forming and non-motile bacterium,
      designated PN1(T), was isolated from a banana leaf collected in Mattra island,
      Thailand. This isolate was observed to grow optimally at 30  degrees C and pH
      7.0, and to grow with 0-3 % NaCl. Comparative 16S rRNA gene sequence analysis
      showed that strain PN1(T) is closely related to members of the genus Roseomonas,
      exhibiting the highest 16S rRNA gene sequence similarity to Roseomonas aestuarii
      JC17(T) (96.5 %). The DNA G + C content of strain PN1(T) was determined to be
      69.7 mol %. Based on physiological and biochemical tests, and genotypic
      differences between strain PN1(T) and the validly named species of the genus
      Roseomonas, it is proposed that the strain be classified as a new species of
      Roseomonas for which the name Roseomonas musae sp. nov. is proposed. The type
      strain is PN1(T) (= BCC 44863(T) = NBRC 107870(T)).

PMID- 23142860
TI  - The putative alpha/beta-hydrolases of Dietzia cinnamea P4 strain as potential
      enzymes for biocatalytic applications.
AB  - The draft genome of the soil actinomycete Dietzia cinnamea P4 reveals a versatile
      group of alpha/beta-hydrolase fold enzymes. Phylogenetic and comparative sequence
      analyses were used to classify the alpha/beta-hydrolases of strain P4 into six
      different groups: (i) lipases, (ii) esterases, (iii) epoxide hydrolases, (iv)
      haloacid dehalogenases, (v) C-C breaking enzymes and (vi) serine peptidases. The
      high number of lipases/esterases (41) and epoxide hydrolase enzymes (14) present
      in the relatively small (3.6 Mb) P4 genome is unusual; it is likely to be linked
      to the survival of strain P4 in its natural environment. Strain P4 is thus
      equipped with a large number of genes which would appear to confer survivability
      in harsh hot tropical soil. As such, this highly resilient soil bacterial strain
      provides an interesting genome for enzyme mining for applications in the field of
      biotransformations of polymeric compounds.

PMID- 23142861
TI  - Arthroscopic-assisted hook plate fixation for acromioclavicular joint
      dislocation.
AB  - PURPOSE: We present a new technique of arthroscopic-assisted AC-hook plate
      fixation for acromioclavicular joint dislocation with all the advantages of
      minimally invasive surgery and the possibility to treat concomitant pathologies.
      METHODS: Initially a glenohumeral arthroscopy is performed to address concomitant
      intra-articular injuries. Under subacromial visualisation the drill hole for the
      hook of the plate can be exactly positioned in the acromion. The hook plate is
      put in place under visual control. RESULTS: The initial results (n = 3) are
      promising with good to excellent results in the Constant score [90.5 (range 82
      100)] in all cases studied. The cross-body test was slightly positive in one
      case. The median follow-up time after the index procedure was seven months (range
      five to ten). CONCLUSIONS: In conclusion, arthroscopic-assisted reconstruction of
      acromioclavicular joint separation is feasible and may provide patients with all
      the benefits of AC-hook fixation with decreased risks related to open surgery.
      The described technique is recommended for all surgeons familiar with
      arthroscopic surgery.

PMID- 23142862
TI  - SPECT/CT tracer uptake is influenced by tunnel orientation and position of the
      femoral and tibial ACL graft insertion site.
AB  - PURPOSE: SPECT/CT is a hybrid imaging modality, which combines a 3D scintigraphy
      (SPECT) and a conventional computerised tomography (CT). SPECT/CT allows accurate
      anatomical localisation of metabolic tracer activity. It allows the correlation
      of surgical factors such as tunnel position and orientation with mechanical
      alignment, clinical outcome and biological factors. The purpose of this study was
      to investigate whether the SPECT/CT tracer uptake (intensity and distribution)
      correlates with the stability and laxity of the knee joint and the position and
      orientation of the tibial and femoral tunnels in patients after anterior cruciate
      ligament (ACL) reconstruction. METHODS: A consecutive series of knees (n=66),
      with symptoms of pain and/or instability after ACL reconstruction were
      prospectively evaluated using clinical examination and 99mTc-HDP-SPECT/CT.
      Clinical laxity testing was performed using the Rolimeter (Ormed, Freiburg,
      Germany) including Lachman testing (0-2 mm, 3-5 mm, 6-10 mm, >10 mm), anterior
      drawer test (0-2 mm, 3-5 mm, 6-10 mm, >10 mm), pivot shift test (positive versus
      negative) and patient-based subjective instability (yes versus no). For analysis
      of SPECT/CT tracer uptake a previously validated SPECT/CT localisation scheme
      consisting of 17 tibial, nine femoral and four patellar regions on standardised
      axial, coronal, and sagittal slices was used. The tracer activity on SPECT/CT was
      localised and recorded using a 3D volumetric and quantitative analysis software.
      Mean, standard deviation, minimum and maximum of grading for each area of the
      localisation scheme were recorded. The position and orientation of the tibial and
      femoral tunnel was assessed using a previously published method on 3D-CT.
      RESULTS: Correlation of instability, pivot shift as well as clinical laxity
      testing with 99mTc-HDP-SPECT/CT tracer uptake intensity and distribution showed
      no significant correlation. 99mTc-HDP-SPECT/CT tracer uptake correlated
      significantly with the position and orientation of the ACL graft. A more
      horizontal femoral graft position showed significantly increased tracer uptake
      within the superior and posterior femoral regions. A more posteriorly-placed
      femoral insertion site showed significantly more tracer uptake within the femoral
      and tibial tunnel regions. A more vertical or a less medial tibial tunnel
      orientation showed significant increased uptake within the tibial and femoral
      tunnel regions. A more anterior tibial tunnel position showed significantly more
      tracer uptake in the femoral and tibial tunnel regions as well as the entire
      tibiofemoral joint. CONCLUSIONS: SPECT/CT tracer uptake intensity and
      distribution showed a significant correlation with the femoral and tibial tunnel
      position and orientation in patients with symptomatic knees after ACL
      reconstruction. No correlation was found with stability or clinical laxity.
      SPECT/CT tracer uptake distribution has the potential to give us important
      information on joint homeostasis and remodelling after ACL reconstruction. It
      might help to predict ACL graft failure and improve our surgical ACL
      reconstruction technique in finding the optimal tunnel and graft position and
      orientation.

PMID- 23142863
TI  - Pain reduction following vertebroplasty and kyphoplasty.
AB  - PURPOSE: To evaluate the clinical efficacy, especially the pain reduction, of
      vertebroplasty and balloon kyphoplasty in the treatment of osteoporotic vertebral
      compression fractures (OVCFs). METHODS: Eighty-six patients with OVCFs were
      treated with vertebroplasty or balloon kyphoplasty. All patients were followed up
      for seven-36 months. Visual analog scale (VAS), vertebral height, and local
      kyphotic angle were evaluated at pre-operation, postoperation, and final follow
      up. RESULTS: The VAS pain score decreased significantly after surgery in both
      kyphoplasty and vertebroplasty groups (p < 0.001), and the improvement of VAS
      score had no significant difference between the two groups (p = 0.826). There was
      a significant difference in the improvement of vertebral height (p < 0.001) and
      local kyphotic angle (p < 0.001) between the two groups. Improvement of VAS score
      had no correlation with improvement of vertebral height (vertebroplasty: r = 
      0.029, p = 0.869; kyphoplasty: r = 0.175, p = 0.219) or local kyphotic angle
      (vertebroplasty: r = 0.159, p = 0.361; kyphoplasty: r = 0.144, p = 0.312) in
      either group. CONCLUSION: Vertebroplasty and kyphoplasty are effective procedures
      for the reduction of pain in OVCFs, and they have the same efficient effect on
      pain reduction. Correction of vertebral height and local kyphosis may have
      minimal effect on pain reduction.

PMID- 23142864
TI  - Performance of cystatin C-based equations in a pediatric cohort at high risk of
      kidney injury.
AB  - BACKGROUND: Limited data exist on the performance of cystatin C-based glomerular
      filtration rate (GFR) equations in pediatric transplant recipients and other high
      risk patients. The aim of our study was therefore to evaluate the performance of
      current cystatin C-based equations in this population. METHODS: This was a
      retrospective, cross-sectional study of 141 consecutive patients (58 % post
      transplant) who received a nuclear medicine GFR (NucGFR) examination using
      (99m)Tc- diethylenetriaminepentaacetic acid at our institution. Subjects included
      children receiving liver, kidney or hematopoietic stem cell transplants and
      patients with oncologic or urologic disease. GFR estimates using published GFR
      estimating equations, including those based on cystatin C (Filler, Zappitelli,
      Larsson, Hoek, Rule and Le Bricon equations, respectively) and on both cystatin C
      and creatinine (Zappitelli, Bouvet and Schwartz equations, respectively), were
      evaluated and compared to the NucGFR measurement using Bland-Altman analysis.
      RESULTS: The mean NucGFR was 95 (interquartile range 76-111) ml/min/1.73 m(2). Of
      the cystatin C-based equations, the Rule, Hoek, Zappitelli and Schwartz (2009
      CKiD equation) formulas provided the closest agreement to the NucGFR estimate.
      All other formulas overestimated the GFR in our cohort. CONCLUSION: Cystatin C
      based GFR formulas can provide an accurate estimation of NucGFR in a pediatric
      population with a high proportion of transplant recipients and oncology patients.

PMID- 23142865
TI  - Insulin resistance in primary nephrotic syndrome; is kidney function truly
      normal?

PMID- 23142866
TI  - Disorders of calcium and magnesium balance: a physiology-based approach.
AB  - Disorders of calcium and magnesium balance are physiologically interesting and
      clinically challenging. In this review, we attempt to bridge the gap between
      physiology and practice by providing a physiology-based approach to understanding
      hypocalcemia, hypercalcemia and hypomagnesemia. Calcium and, to a lesser extent,
      magnesium balance is achieved through a complex interplay between the parathyroid
      gland, bone, the intestine and the kidney. Our understanding of the molecular
      physiology of calcium and magnesium balance has grown considerably following the
      discovery of the calcium-sensing receptor (CaSR) and the main intestinal and
      renal transporters for calcium and magnesium, namely, the transient receptor
      potential channels TRPV5, TRPV6 and TRPM6. The regulation of parathyroid hormone
      (PTH) secretion by CaSR and the subsequent effects of PTH and vitamin D on TRPV5
      constitute an increasingly characterized regulatory loop. In contrast, no truly
      magnesiotropic hormones have been identified, although the recently established
      interactions between the epidermal growth factor and TRPM6 suggest a possible
      candidate. Overall, the aim of this review is to illustrate the clinical
      disorders of calcium and magnesium balance from the perspective of their
      integrated physiology. 

PMID- 23142867
TI  - Preoperative prediction of acute kidney injury--from clinical scores to
      biomarkers.
AB  - Early acute kidney injury (AKI) diagnosis in critically ill children has been an
      important recent research focus because of the known association of AKI with poor
      outcomes and the requirement of early intervention to mitigate negative effects
      of AKI. In children having surgery, the preoperative period offers a unique
      opportunity to predict postoperative acute kidney injury (AKI), well before AKI
      occurs. Pediatric AKI epidemiologic studies have begun to identify which
      preoperative factors may predict development of postoperative cardiac surgery.
      Using these clinical risk factors, it may be possible to derive preoperative
      clinical risk scores and improve upon our ability to risk-stratify children into
      AKI treatment trials, pre-emptively provide conservative renal injury prevention
      strategies, and ultimately improve patient outcomes. Developing risk scores
      requires rigorous methodology and validation before widespread use. There is
      little information currently on the use of preoperative biological or
      physiological biomarkers to predict postoperative AKI, representing an important
      area of future research. This review will provide an overview of methodology of
      preoperative risk score development, discuss pediatric-specific issues around
      deriving such risk scores, including the combination of preoperative clinical and
      biologic biomarkers for AKI prediction, and suggest future research avenues. 

PMID- 23142868
TI  - High photostability and enhanced fluorescence of gold nanoclusters by silver
      doping.
AB  - Gold nanoclusters prepared with a controlled amount of Ag exhibit intense
      fluorescence with a quantum yield of ~16% and a "quasi-monoexponential" long
      lifetime of >200 ns. Characterization of the luminescent probes indicates high
      photostability and easy detection in cells. Additionally, fluorescence
      enhancement in the presence of proteins was found.

PMID- 23142869
TI  - De novo derivation of proteomes from transcriptomes for transcript and protein
      identification.
AB  - Identification of proteins by tandem mass spectrometry requires a reference
      protein database, but these are only available for model species. Here we
      demonstrate that, for a non-model species, the sequencing of expressed mRNA can
      generate a protein database for mass spectrometry-based identification. This
      combination of high-throughput sequencing and protein identification technologies
      allows detection of genes and proteins. We use human cells infected with human
      adenovirus as a complex and dynamic model to demonstrate the robustness of this
      approach. Our proteomics informed by transcriptomics (PIT) technique identifies
      >99% of over 3,700 distinct proteins identified using traditional analysis that
      relies on comprehensive human and adenovirus protein lists. We show that this
      approach can also be used to highlight genes and proteins undergoing dynamic
      changes in post-transcriptional protein stability.

PMID- 23142870
TI  - Membrane-protein structure determination by solid-state NMR spectroscopy of
      microcrystals.
AB  - Membrane proteins are largely underrepresented among available atomic-resolution
      structures. The use of detergents in protein purification procedures hinders the
      formation of well-ordered crystals for X-ray crystallography and leads to slower
      molecular tumbling, impeding the application of solution-state NMR. Solid-state
      magic-angle spinning NMR spectroscopy is an emerging method for membrane-protein
      structural biology that can overcome these technical problems. Here we present
      the solid-state NMR structure of the transmembrane domain of the Yersinia
      enterocolitica adhesin A (YadA). The sample was derived from crystallization
      trials that yielded only poorly diffracting microcrystals. We solved the
      structure using a single, uniformly (13)C- and (15)N-labeled sample. In addition,
      solid-state NMR allowed us to acquire information on the flexibility and mobility
      of parts of the structure, which, in combination with evolutionary conservation
      information, presents new insights into the autotransport mechanism of YadA.

PMID- 23142871
TI  - A toolkit and benchmark study for FRET-restrained high-precision structural
      modeling.
AB  - We present a comprehensive toolkit for Forster resonance energy transfer (FRET)
      restrained modeling of biomolecules and their complexes for quantitative
      applications in structural biology. A dramatic improvement in the precision of
      FRET-derived structures is achieved by explicitly considering spatial
      distributions of dye positions, which greatly reduces uncertainties due to
      flexible dye linkers. The precision and confidence levels of the models are
      calculated by rigorous error estimation. The accuracy of this approach is
      demonstrated by docking a DNA primer-template to HIV-1 reverse transcriptase. The
      derived model agrees with the known X-ray structure with an r.m.s. deviation of
      0.5 A. Furthermore, we introduce FRET-guided 'screening' of a large structural
      ensemble created by molecular dynamics simulations. We used this hybrid approach
      to determine the formerly unknown configuration of the flexible single-strand
      template overhang.

PMID- 23142872
TI  - Systematic reconstruction of RNA functional motifs with high-throughput
      microfluidics.
AB  - We present RNA-mechanically induced trapping of molecular interactions (RNA
      MITOMI), a microfluidic platform that allows integrated synthesis and functional
      assays for programmable RNA libraries. The interaction of a comprehensive library
      of RNA mutants with stem-loop-binding protein precisely defined the RNA
      structural and sequence features that govern affinity. The functional motif
      reconstructed in a single experiment on our platform uncovers new binding
      specificities and enriches interpretation of phylogenetic data.

PMID- 23142873
TI  - Two-photon optogenetics of dendritic spines and neural circuits.
AB  - We demonstrate a two-photon optogenetic method that generates action potentials
      in neurons with single-cell precision, using the red-shifted opsin C1V1(T). We
      applied the method to optically map synaptic circuits in mouse neocortical brain
      slices and to activate small dendritic regions and individual spines. Using a
      spatial light modulator, we split the laser beam onto several neurons and
      performed simultaneous optogenetic activation of selected neurons in three
      dimensions.

PMID- 23142874
TI  - Uncertainties of forest area estimates caused by the minimum crown cover
      criterion--a scale issue relevant to forest cover monitoring.
AB  - Defining "forest land" is a complex issue and has been discussed for decades.
      Today, a confusing multitude of definitions of forest land are in use making
      comparison of forest area figures difficult. But currently, comparability is
      receiving much attention when it comes to install market mechanisms for ecosystem
      services. Minimum crown cover is among the most frequently employed criteria of
      forest definitions. However, the size of the reference area on which the crown
      cover percent is to be measured is usually not defined. But how does a change of
      the size of the reference area affect the derived forest cover? In this study, we
      analyze the interactions of the crown cover threshold and the size of the
      reference area. We start with analyzing the interactions using a simple geometric
      model of the forest edge. Then, we extend the analysis by simulating artificial
      landscapes where we study how the interaction is affected by different degrees of
      forest fragmentation, crown cover proportion, and spatial resolution of the data
      source used. The simulation showed that large differences in forest cover (>50 %)
      may result for a fixed crown cover threshold value, just by changing the size of
      the reference area, where the magnitude of this effect is a function of the
      chosen threshold value and the spatial configuration of the crowns. As a
      consequence of the findings, we see an urgent need to complete forest definitions
      by defining a reference area in order to reduce uncertainties of forest cover
      estimates.

PMID- 23142875
TI  - Heavy metals and essential elements in Commerson's dolphins (Cephalorhynchus c.
      commersonii) from the southwestern South Atlantic Ocean.
AB  - A survey of the elemental contents of K, Mg, Mn, Na, Cl, Br, Cs, Co, Rb, Fe, Zn,
      Al, Ti, V, As, Ag, Au and Cd in liver, kidney and muscle was performed in
      specimens of Commerson's dolphins (Cephalorhynchus c. commersonii) from
      subantarctic waters. The concentrations were determined by Instrumental Neutron
      Activation Analysis and the specimens derives from animals incidentally caught in
      artisanal fishing nets. Liver had the highest concentrations of Fe, 897(79) MUg
      g(-1) DW (dry weight) (average; standard deviation in parenthesis), kidney had
      the highest Cd, 35 (24) MUg g(-1) DW; Cl, 9,200 (1,700) MUg g(-1) DW; Na, 6,800
      (1,100) MUg g(-1) DW and Br, 73(12) MUg g(-1) DW; and muscle the highest Mg 954
      (71) MUg g(-1) DW. Potassium and Cs concentrations in muscle and kidney ranged in
      12,510-13,020 and 0.230-0.252 MUg g(-1) DW, respectively; Zn and Mn
      concentrations were similar in liver and kidney (117-122.1 and 3.66-16.5 MUg g(
      1) DW, respectively). Silver was high in liver 5.4(5.0) MUg g(-1) DW and kidney
      1.2(2.7) MUg g(-1) DW. Gold, Rb, Co and As had no differences among tissues.
      Likewise, as in other odontocete species, the concentrations of essential
      elements showed little variation between the specimens analyzed, since they are
      regulated biochemically; however, heavy metals showed high variability. This
      study constitutes the first large description of the elemental composition in
      Commerson's dolphins from subantarctic waters of the South Atlantic Ocean.

PMID- 23142876
TI  - Effect of low-molecular-weight organic acids on kinetics release and
      fractionation of phosphorus in some calcareous soils of western Iran.
AB  - Organic acid has been related to nutrient mobilization, mainly in phosphorus (P)
      insoluble utilization, and therefore enhances P bioavailability. In this study,
      we examined the effect of low-molecular-weight organic acids (malic, citric, and
      oxalic acids) on P release of some calcareous soils from western Iran.
      Fractionation and speciation of P in the soil solution were studied at the
      initial and final P release. Significantly different quantities of P were
      extracted by the organic acids. On average the maximum (1,554.9 mg kg(-1)) and
      the minimum (1,260.5 mg kg(-1)) P were extracted by 10 mM oxalic and malic acid,
      respectively. Power equation described well P release. In the initial stage of P
      release, the solution samples in soils were supersaturated with respect to
      hydroxyapatite and beta-TCP. At the end of P release, all solutions were
      undersaturated with phosphate minerals. The percentage of Fe-Al oxide fraction
      generally increased after P release, while carbonate and residual P fractions
      were decreased in all organic acids. Compared with the native soils, adding malic
      and citric acids had no effect on Fe-Al oxide fraction, but oxalic acid
      significantly reduced this fraction.

PMID- 23142877
TI  - Does stream water chemistry reflect watershed characteristics?
AB  - In this study, we investigated the relationships between stream water chemistry
      and watershed characteristics (topography--mean altitude and slope; climate--mean
      annual temperature and precipitation; geology--geochemical reactivity; land
      cover; inhabitation--population density, road density and number of
      municipalities). We analyzed the concentrations of the major anions (Cl, F, NO3,
      SO4, SiO2), cations (Ca, Mg, Na, K, Mn, Fe, Al), trace elements (Li, Sr, Cu),
      ABS245, TDP (total dissolved phosphorus), pH, and conductivity at 3,220 diverse
      watersheds covering a wide variety of watershed characteristics in the Czech
      Republic. We used marginal and partial multivariate analyses to reveal the most
      important variables. The partial analysis showed that only 14% of the variance
      could be assigned to a specific factor and that 41% of the variance is shared
      among the factors, which indicated complex interactions between the watershed
      characteristics.

PMID- 23142878
TI  - Effects of visitor pressure on understory vegetation in Warsaw forested parks
      (Poland).
AB  - Visitor's access to understorey vegetation in park forest stands results in the
      impoverishment of plant species composition and a reduction in habitat quality.
      The phenomenon of biotic homogenisation is typical in urban landscapes, but it
      can proceed differently depending on the scale, a detail that has not been
      observed in previous studies. This research was carried out in seven Warsaw parks
      (both public and restricted access). Thirty-four forested areas were randomly
      selected, some subjected to strong visitors' pressure and some within restricted
      access areas, free of such impacts. The latter category included woodlands
      growing in old forest and secondary habitats. Public access to the study areas
      contributed to the disappearance of some forest species and their replacement by
      cosmopolitan non-forest species, leading to loss of floristic biodiversity in
      areas of high ecological importance at the city scale. Some human-induced
      factors, including soil compaction and changes in soil pH, moisture and capillary
      volume, were found to cause habitat changes that favoured native non-forest
      plants. Despite changes in species composition, the taxonomic similarity of
      understorey vegetation in both categories--public access and restricted access-
      was comparable. In a distance gradient of measurements taken around selected
      individual trees, there was found to be significant variation (in light, soil pH
      and compaction) affecting the quality and quantity of understorey vegetation
      (including rare species). In conclusion, the protection of rare forest species
      could be achieved by limiting access to forested areas, particularly in old
      forest fragments, and we highly recommend its consideration in the proposal of
      future park restoration plans.

PMID- 23142879
TI  - Metastatic melanoma from unknown primary presenting as dorsal midbrain syndrome.
AB  - PURPOSE.: Dorsal midbrain syndrome, which is characterized by upgaze paralysis,
      light-near dissociated pupils, eyelid retraction, and convergence retraction
      nystagmus, can be caused by compression, ischemia, inflammation, or injury to the
      dorsal midbrain. Although brain metastases are common in certain cancers,
      including melanoma, only 3 to 5% occur in the brain stem. We present a case of
      metastatic melanoma from an unknown primary that initially presented as dorsal
      midbrain syndrome. CASE REPORT.: After a prodrome of intermittent nonspecific
      visual symptoms, a 60-year-old male veteran presented with bilateral upgaze
      paralysis and convergence retraction nystagmus. A single hemorrhagic lesion in
      the midbrain was causative. An inguinal mass with associated lymphadenopathy was
      subsequently discovered, and the biopsy from this site revealed malignant
      melanoma. A primary lesion was never found. The patient underwent surgical
      resection of the groin lesion and stereotactic radiosurgery for the midbrain
      metastasis but passed away 6 months after his initial presentation. CONCLUSIONS.:
      The presentation of bilateral vertical gaze paralysis, especially in the company
      of convergence retraction nystagmus, light-near dissociated pupils, or eyelid
      retraction, should raise concern for midbrain pathology. Although metastases to
      the midbrain are rare, they carry a grave prognosis, especially if melanoma is
      the primary malignancy, and most treatment options are considered palliative.

PMID- 23142880
TI  - Moxifloxacin resistance:  intrinsic to antibiotic or related to mutation?
AB  - PURPOSE: To evaluate and compare the pattern of resistance to topical
      moxifloxacin of ocular isolates recovered during comparable periods within 2
      years. METHODS: Records of 611 consecutive cases of bacterial corneal ulcers that
      presented to our center between April and August 2007 were compared with records
      of 417 cases that presented in April and August 2006. Records of culture and
      sensitivity to cefazolin, tobramycin, gatifloxacin, and moxifloxacin at the time
      of presentation were analyzed. Parameters recorded included total number of cases
      in each period, culture-positive cases, organisms isolated, and sensitivity by
      Kirby-Bauer disk-diffusion test. The data from 2007 was compared with those from
      2006 using chi test. RESULTS: Culture-positive rate was 70.2% in 2007 compared
      with 65.0% in 2006 (p = 0.143). The percentage of culture-positive cases
      resistant to moxifloxacin was 5.46% in 2007 compared with 5.42% in 2006 (p =
      0.977). There was no significant difference between resistance against cefazolin
      during the two periods (p = 0.895). Resistance to gatifloxacin and tobramycin was
      significantly higher in samples tested in 2007 as compared with those tested in
      2006 (gatifloxacin, p = 0.037; tobramycin, p = 0.031). CONCLUSIONS: Resistance to
      moxifloxacin did not change significantly during a period of 2 years in our
      study. The static resistance pattern to moxifloxacin may indicate that such
      resistance to moxifloxacin is intrinsic in the antibiotic rather than new
      resistance stemming from mutations.

PMID- 23142881
TI  - Refraction in children:  a comparison of two methods of accommodation control.
AB  - PURPOSE: The prevalence of refractive errors in children has been extensively
      researched. Comparisons between studies can, however, be compromised because of
      differences between accommodation control methods and techniques used for
      measuring refractive error. The aim of this study was to compare spherical
      refractive error results obtained at baseline and using two different
      accommodation control methods-extended optical fogging and cycloplegia-for two
      measurement techniques-autorefraction and retinoscopy. METHODS: Participants
      included 25 school children aged 6 to 13 years (mean age, 9.52 +/- 2.06 years).
      The refractive error of one eye was measured at baseline and again under two
      different accommodation control conditions: extended optical fogging (+2.00DS for
      20 minutes) and cycloplegia (1% cyclopentolate). Autorefraction and retinoscopy
      were both used to measure the most plus spherical power for each condition.
      RESULTS: A significant interaction was demonstrated between measurement technique
      and accommodation control method (p = 0.036), with significant differences in
      spherical power evident between accommodation control methods for each of the
      measurement techniques (p < 0.005). For retinoscopy, refractive errors were
      significantly more positive for cycloplegia compared with optical fogging, which
      were in turn significantly more positive than baseline; whereas for
      autorefraction, there were significant differences between cycloplegia and
      extended optical fogging and between cycloplegia and baseline only. CONCLUSIONS:
      Determination of refractive error under cycloplegia elicits more plus than using
      extended optical fogging as a method to relax accommodation. These findings
      support the use of cycloplegic refraction compared with extended optical fogging
      as a means of controlling accommodation for population-based refractive error
      studies in children.

PMID- 23142882
TI  - Micro energy dispersive x-ray fluorescence as a powerful complementary technique
      for the analysis of bimetallic Au/Ag/glass nanolayer composites used in surface
      plasmon resonance sensors.
AB  - It is demonstrated that any theoretical analysis of experimental surface plasmon
      resonance (SPR) curves of metallic nano bilayers preferably should be accompanied
      by a more sensitive technique that is less prone to experimental errors. Micro
      energy dispersive x-ray fluorescence has been shown to be a powerful technique
      for predicting SPR angle and assessing Au/Ag nanolayer composite spatial
      homogeneity.

PMID- 23142883
TI  - High-efficiency Fresnel lens fabricated by axially symmetric photoalignment
      method.
AB  - In this study, a Fresnel lens with radial and azimuthal liquid crystal (LC)
      alignments in the odd and even zones was fabricated using the photoalignment
      technique based on an azo dye doped in LC cells. The lens has approximately 35%
      focusing efficiency as determined using a linearly polarized probe beam. In
      addition, the lens converts the input linear polarization into axially
      symmetrical polarization at the focal plane. The fabricated Fresnel lens is
      polarization-independent and has electrically controllable focusing efficiency.
      Moreover, the far-field pattern of a probe beam through the device placed between
      the polarizers agrees with the pattern obtained from the simulation.

PMID- 23142884
TI  - Portable fiber group velocity test method with a gain-switched laser.
AB  - A portable method of group velocity measurement is proposed based on a self
      seeded gain-switched laser. The calculated group velocity in the optical fiber is
      obtained by measuring the round-trip frequencies of the gain-switched laser diode
      with different external cavities, and only a 2 m long fiber is needed. The
      measurement can be accomplished without oscilloscope or optical spectrum
      analyzer. The error associated with this test is within 0.65%, which is limited
      by the jitter of the voltage-controlled oscillator. Its spectrum resolution is
      0.1 nm.

PMID- 23142885
TI  - Optical hierarchical authentication based on interference and hash function.
AB  - We propose a method to achieve the purpose of hierarchical authentication on the
      basis of two beams' interference and the one-way hash function. For this security
      protection system, only if the "phase key" and the password-controlled "phase
      lock" of a user are verified simultaneously can one obtain a permission to visit
      the confidential resources of the system. Moreover, this scheme can not only
      check the legality of the users but also verify their identity levels so as to
      grant them corresponding hierarchical access permissions. The authentication
      process is straightforward; the phase key and the password-controlled phase lock
      of one user are loading on two spatial light modulators in advance, by which two
      coherent beams are modulated and then interfere with each other at the output
      plane leading to an output image. By comparing the output image with all the
      standard certification images in the database, the system can thus verify the
      user's identity. However, the system designing process involves an iterative
      modified phase retrieval algorithm. For an authorized user, a phase lock is first
      created based on a "digital fingerprint," which is the result of a hash function
      on a preselected user password. The corresponding phase key can then be
      determined by use of the phase lock and a designated standard certification
      image. Theoretical analysis and computer simulations both validate the
      effectiveness of our method.

PMID- 23142886
TI  - Photodarkening kinetics as a function of Yb concentration and the role of Al
      codoping.
AB  - We investigated the photodarkening (PD) kinetics of two fiber series with
      variation of the Yb content for constant Al concentration or constant ratio of
      Al/Yb, respectively. The results show the outstanding importance of the absolute
      value of Al concentration also in the case of fibers with strongly reduced Yb
      content. An Al/Yb ratio of 5 to 6 is not sufficient to mitigate PD loss.
      Moreover, a model to describe PD loss and rate constant as functions of Yb
      concentration and excitation is suggested that links measurements of PD in single
      fibers of the same type (variation of Yb inversion) and in fiber series (constant
      Yb inversion).

PMID- 23142887
TI  - Analysis of spatial hole burning and temperature effects in vertical-cavity
      surface-emitting lasers with internal photonic crystal waveguide.
AB  - We investigate theoretically the effect of two-dimensional photonic crystal (PC)
      defect waveguide parameters embedded into vertical-cavity surface-emitting lasers
      (VCSELs) on static operation of PC-VCSEL, including spatial hole burning (SHB)
      and temperature in the active regions. In structures with larger pitch of PC
      holes, SHB occurs dramatically and temperature increases in the active region. In
      large-hole diameter to pitch ratio, SHB has little effect and temperature is
      decreased in the active regions. We also show that with higher input current,
      temperature rises and SHB occurs.

PMID- 23142888
TI  - Refractive index investigation of poly(vinyl alcohol) films with TiO2
      nanoparticle inclusions.
AB  - The refractive index (RI) of polymer nanocomposite of poly(vinyl alcohol) films
      with TiO(2) nanoparticle inclusions with low concentration up to 1.2 wt. % was
      investigated. Accurate refractometric measurements, by a specially designed laser
      microrefractometer, were performed at wavelengths 532 and 632.8 nm. The influence
      of TiO(2) concentration on the RI dispersion curves was predicted based on the
      well-known Sellmeier model. The theoretical analysis, in a small filling factor
      approximation, was performed, and a relation between the effective RI of the
      nanocomposite and weight concentrations of the TiO(2) nanofiller was derived. The
      experimental values were approximated by two different functions (linear and a
      quadratic polynom). The polynomial approximation yields better result, where
      R(2)=0.90.

PMID- 23142889
TI  - Adjustable bipod flexures for mounting mirrors in a space telescope.
AB  - A new mirror mounting technique applicable to the primary mirror in a space
      telescope is presented. This mounting technique replaces conventional bipod
      flexures with flexures having mechanical shims so that adjustments can be made to
      counter the effects of gravitational distortion of the mirror surface while being
      tested in the horizontal position. Astigmatic aberration due to the gravitational
      changes is effectively reduced by adjusting the shim thickness, and the relation
      between the astigmatism and the shim thickness is investigated. We tested the
      mirror interferometrically at the center of curvature using a null lens. Then we
      repeated the test after rotating the mirror about its optical axis by 180 degrees
      in the horizontal setup, and searched for the minimum system error. With the
      proposed flexure mount, the gravitational stress at the adhesive coupling between
      the mirror and the mount is reduced by half that of a conventional bipod flexure
      for better mechanical safety under launch loads. Analytical results using finite
      element methods are compared with experimental results from the optical
      interferometer. Vibration tests verified the mechanical safety and optical
      stability, and qualified their use in space applications.

PMID- 23142890
TI  - Proposal for tunable dual channel transmitter and mechano-optical switch based on
      photonic crystal.
AB  - In this article we propose a novel mechano-optical switch and dual channel
      transmitter based on photonic crystal. The device consists of two waveguides and
      an elliptical cavity in a square lattice structure. Two optical signals at
      separate wavelengths are inserted in the input waveguide. The elliptical cavity
      can be rotated using a mechanical force, which results in the control of
      transmission efficiency at each of the wavelengths. In addition, rotation of the
      cavity can be considered as a switching action, which changes on-off states of
      the output signals.

PMID- 23142891
TI  - All-optical switching of a single wavelength in a silicon-based ring-assisted
      Mach-Zehnder interferometer.
AB  - We theoretically investigate for the first time an all-optical switch using a
      silicon-based ring-assisted Mach-Zehnder interferometer (RAMZI), where the switch
      mechanism relies on Raman-induced loss. Compared to the conventional standalone
      microring resonator (MRR) switches, the RAMZI structure improves the fabrication
      tolerances by removing the critical coupling requirement for the MRR without
      compensating the switch performance. Moreover, the RAMZI structure provides an
      improved switching speed (5* faster) by shortening the photon lifetime of the
      MRR. Finally, the inverse Raman scattering of silicon guarantees a single
      wavelength selectivity for the switch.

PMID- 23142892
TI  - Influence of symmetry breaking in a planar metamaterial on transparency effect
      and sensing application.
AB  - The influence of symmetry breaking in a planar metamaterial on transparency
      effect is numerically investigated. The planar metamaterial's cell is formed by
      three parallel metal wires. From numerical simulation results, we can see that
      the transparency effect results from the asymmetric coupling between the cut
      wires. The excited mechanism of the transparency effect is further analyzed by
      using the hybridization concept. It is found that the coupling fields between the
      cut wires play key roles and lead to the spectral splitting of the resonance,
      i.e., the classical electromagnetically induced transparency effect. The
      metamaterial sensor based on the refractive index variation of the surrounding
      material is also numerically demonstrated and yields a sensitivity of 9.47 mm/RIU
      and a figure of merit of 13.5. In addition, the spectral response of the
      metamaterial is quantitatively described via the "three-particle" model. The
      analytically calculated results of the model show a good agreement with the
      simulation results.

PMID- 23142893
TI  - Integrated optofluidic system for monitoring particle mass concentrations based
      on planar emitter-receiver units.
AB  - We demonstrate an integrated optofluidic system for monitoring the particle mass
      concentration and the Sauter mean diameter of polydisperse flowing suspensions of
      water and standardized test dust. For optimum integration, a planar emitter
      receiver unit is developed and fabricated on Si technology. A vertical cavity
      surface emitting laser at 850 nm serves as light source, and monolithically
      integrated segmented photodiodes detect both the attenuation of the primary light
      beam and the scattered light. The optical system is integrated into a planar
      transparent polymethylmethacrylate substrate by micromilling of an optical
      freeform surface and electron beam evaporation of reflective layers following the
      concept of planar integrated free-space optical systems. We are able to detect 1
      mg/L of the standards ISO 12103-A2 (fine test dust), -A3 (medium test dust), and 
      A4 (coarse test dust) and to determine the Sauter mean diameter of the particle
      size distribution.

PMID- 23142894
TI  - Modeling and validation of photometric characteristics of space targets oriented
      to space-based observation.
AB  - A modeling and validation method of photometric characteristics of the space
      target was presented in order to track and identify different satellites
      effectively. The background radiation characteristics models of the target were
      built based on blackbody radiation theory. The geometry characteristics of the
      target were illustrated by the surface equations based on its body coordinate
      system. The material characteristics of the target surface were described by a
      bidirectional reflectance distribution function model, which considers the
      character of surface Gauss statistics and microscale self-shadow and is obtained
      by measurement and modeling in advance. The contributing surfaces of the target
      to observation system were determined by coordinate transformation according to
      the relative position of the space-based target, the background radiation
      sources, and the observation platform. Then a mathematical model on photometric
      characteristics of the space target was built by summing reflection components of
      all the surfaces. Photometric characteristics simulation of the space-based
      target was achieved according to its given geometrical dimensions, physical
      parameters, and orbital parameters. Experimental validation was made based on the
      scale model of the satellite. The calculated results fit well with the measured
      results, which indicates the modeling method of photometric characteristics of
      the space target is correct.

PMID- 23142895
TI  - Three-dimensional reconstruction of laser-imploded targets from simulated pinhole
      images.
AB  - This paper proposes an integral method to achieve a more accurate weighting
      matrix that makes very positive contributions to the image reconstruction in
      inertial confinement fusion research. Standard algebraic reconstruction
      techniques with a positivity constraint included are utilized. The final
      normalized mean-square error between the simulated and reconstructed projection
      images is 0.000365%, which is a nearly perfect result, indicating that the
      weighting matrix is very important. Compared with the error between the simulated
      and reconstructed phantoms, which is 2.35%, it seems that the improvement of the
      accuracy of the projection image does not mean the improvement of the phantom.
      The proposed method can reconstruct a simulated laser-imploded target consisting
      of 100*100*100 voxels.

PMID- 23142896
TI  - Bulk laser-induced damage threshold of titanium-doped sapphire crystals.
AB  - The bulk laser-induced damage threshold (LIDT) fluence of Ti:sapphire is
      determined under single-pulse irradiation from the femtosecond to nanosecond
      temporal regimes in the visible and near-infrared spectral domains. In the range
      of explored laser conditions, the LIDT fluence increases with both pulse duration
      and wavelength. The results are also compared to laser interaction with sapphire
      samples and show an increased resistance to laser damage when the material is
      doped with Ti(3+) ions. These conclusions are of interest for robust operation of
      high-peak-power femtosecond Ti:sapphire laser chains.

PMID- 23142897
TI  - Optimization of gain bandwidth and gain ripple of a hybrid Raman/parametric
      amplifier for access network applications.
AB  - We describe the mathematical model and present simulation results for the
      optimization of a hybrid Raman/optical parametric amplifier (HROPA), exhibiting a
      bandwidth of 170 nm and low ripple that covers the top half of the wavelength
      plan (e.g., 1441 to 1611 nm) of next generation coarse wavelength division
      multiplexed passive optical network systems. We show that a critical parameter in
      the proper amplifier parameter optimization is the inclusion of the fourth-order
      dispersion coefficient (beta(4)). Omission of beta(4) can lead to over-estimation
      or underestimation of the gain bandwidth, and hence its inclusion in the analysis
      of the HROPA is necessary.

PMID- 23142898
TI  - Ramsauer approach for light scattering on nonabsorbing spherical particles and
      application to the Henyey-Greenstein phase function.
AB  - We present a new method to study light scattering on nonabsorbing spherical
      particles. This method is based on the Ramsauer approach, a model known in atomic
      and nuclear physics. Its main advantage is its intuitive understanding of the
      underlying physics phenomena. We show that although the approximations are
      numerous, the Ramsauer analytical solutions describe fairly well the scattering
      phase function and the total cross section. Then this model is applied to the
      Henyey-Greenstein parameterization of the scattering phase function to give a
      relation between its asymmetry parameter and the mean particle size.

PMID- 23142899
TI  - Methods used to observe a dynamical quantum nonlocality effect in a twin Mach
      Zehnder interferometer.
AB  - Straightforward novel methods for stabilizing, tuning, and controlling a twin
      Mach-Zehnder interferometer for the purpose of observing a subtle dynamical
      quantum nonlocality effect in a recent optical experiment are presented and
      discussed. Weak measurements were required for observing a subtle quantum
      dynamical nonlocality effect that reveals itself in a change of a weak value.
      Consequently, emphasis is placed upon describing the approaches to apparatus
      stabilization and interaction strength control between photons and the apparatus.
      The details discussed in this paper should be of general interest to
      experimentalists engaging in weak measurement and weak value research.

PMID- 23142900
TI  - Absorption spectroscopy of powdered materials using time-resolved diffuse optical
      methods.
AB  - In this paper a novel method, based on time-resolved diffuse optical
      spectroscopy, is proposed to measure the absorption of small amounts of
      nanostructured powder materials independent of scattering. Experimental
      validation, in the visible and near-infrared spectral range, has been carried out
      on India Ink<sup/>particles. The effectiveness of the technique to measure
      scattering-free absorption is demonstrated on carbon nanotubes. The comparison
      between the absorption spectra acquired by the proposed method and conventional
      measurements performed with a commercial spectrophotometer is discussed.

PMID- 23142901
TI  - Dependence of Brillouin frequency shift on radial and axial strain in silica
      optical fibers.
AB  - Brillouin frequency shift (BFS) in a single-mode optical fiber has been measured
      as a function of both radial and axial strain via the Brillouin optical time
      domain analysis technique. The effects of the two kinds of strain on the BFS are
      decoupled by making fiber pretensioned and relaxed while applying pressure.
      Linear relations have been found between the BFS and both kinds of strain. The
      radial strain coefficient C(vepsilon(r)) is found to be 0.029 MHz/MUepsilon, and
      the axial strain coefficient C(vepsilon(a)) is 0.053 MHz/MUepsilon. The result
      may give impetus to some potential applications of the optical fibers, such as a
      distributed pressure sensor based on Brillouin scattering.

PMID- 23142902
TI  - Numerical simulation of the influence of the elastic modulus of a tumor on laser
      induced ultrasonics in soft tissue.
AB  - The influence of the elastic modulus of a tumor (EMT) on the laser-generated
      thermoelastic force source and ultrasound waves are investigated by using the
      finite element method. Taking into account the effects of thermal diffusion,
      optical penetration, and finite duration of laser pulse, the transient
      temperature distribution is obtained. Applying this temperature field to
      structure analyses as thermal loading, the thermoelastic stress field and laser
      induced ultrasound wave in soft tissues are obtained. The results show that there
      is a linear correlation between the maximum compressive stress and the elastic
      modulus of tissues. It is also shown that the features and frequency regions of
      the laser-induced ultrasound waveform have a close relationship with the EMT,
      which has been further verified by a corresponding experiment.

PMID- 23142903
TI  - Utilization of a liquid crystal spatial light modulator in a gray scale detour
      phase method for Fourier holograms.
AB  - This paper introduces a new modification for the well-known binary detour phase
      method, which is largely used to represent Fourier holograms; the modification
      utilizes gray scale level control provided by a liquid crystal spatial light
      modulator to improve the traditional binary detour phase. Results are shown by
      both simulation and experiment.

PMID- 23142904
TI  - Mesh size in Lichtenstein repair: a systematic review and meta-analysis to
      determine the importance of mesh size.
AB  - PURPOSE: Small mesh size has been recognized as one of the factors responsible
      for recurrence after Lichtenstein hernia repair due to insufficient coverage or
      mesh shrinkage. The Lichtenstein Hernia Institute recommends a 7 * 15 cm mesh
      that can be trimmed up to 2 cm from the lateral side. We performed a systematic
      review to determine surgeons' mesh size preference for the Lichtenstein hernia
      repair and made a meta-analysis to determine the effect of mesh size, mesh type,
      and length of follow-up time on recurrence. METHODS: Two medical databases,
      PubMed and ISI Web of Science, were systematically searched using the key word
      "Lichtenstein repair." All full text papers were selected. Publications
      mentioning mesh size were brought for further analysis. A mesh surface area of 90
      cm(2) was accepted as the threshold for defining the mesh as small or large.
      Also, a subgroup analysis for recurrence pooled proportion according to the mesh
      size, mesh type, and follow-up period was done. RESULTS: In total, 514 papers
      were obtained. There were no prospective or retrospective clinical studies
      comparing mesh size and clinical outcome. A total of 141 papers were duplicated
      in both databases. As a result, 373 papers were obtained. The full text was
      available in over 95 % of papers. Only 41 (11.2 %) papers discussed mesh size. In
      29 studies, a mesh larger than 90 cm(2) was used. The most frequently preferred
      commercial mesh size was 7.5 * 15 cm. No papers mentioned the size of the mesh
      after trimming. There was no information about the relationship between mesh size
      and patient BMI. The pooled proportion in recurrence for small meshes was 0.0019
      (95 % confidence interval: 0.007-0.0036), favoring large meshes to decrease the
      chance of recurrence. Recurrence becomes more marked when follow-up period is
      longer than 1 year (p < 0.001). Heavy meshes also decreased recurrence (p =
      0.015). CONCLUSION: This systematic review demonstrates that the size of the mesh
      used in Lichtenstein hernia repair is rarely discussed in clinical studies.
      Papers that discuss mesh size appear to reflect a trend to comply with the latest
      recommendations to use larger mesh. Standard heavy meshes decrease the recurrence
      in hernia repair. Even though there is no evidence, it seems that large meshes
      decrease recurrence rates.

PMID- 23142905
TI  - Accuracy of targeted post-mortem computed tomography coronary angiography
      compared to assessment of serial histological sections.
AB  - Post-mortem computed tomography with coronary angiography (PMCTA) could have a
      role in the investigation of sudden natural death. This study assesses the
      accuracy of targeted coronary PMCTA, using both air and iodinated contrast media,
      to provide sensitivity and specificity for critical stenosis (CS) on a segmental
      basis, based on a gold standard of 3-5 mm serial sections of the coronary
      arteries using macroscopic and histological techniques. Assessment of stenosis at
      1 mm intervals on PMCTA was compared with the data from pathological analysis.
      Stenosis was defined as "critical" when the stenotic region reaches >=75 %.
      Regions were defined every 20 mm or by a clear change in stenosis. Discrepancies
      were defined as significant if only one test showed CS. Five cases with 25
      vessels with 124 regions were assessed. PMCTA was unable to identify plaque
      hemorrhage or dissection (but this was normally associated with CS). Eighteen
      segments had significant discrepancies, giving a sensitivity and specificity of
      50 and 91.5 %. When an alternative gold standard was constructed by excluding
      regions beyond a CS (five cases), taking PMCTA as correct where a heavily
      calcified vessel opens under contrast injection (four cases), and correcting for
      misregistration of distance (one case), the sensitivity rose to 85.7 %. There was
      complete agreement when the right or left coronary arteries are assessed as a
      whole. This study shows that PMCTA is not a perfect replacement for histological
      examination of coronary vessels, but may have a role in routine post-mortem
      investigation. 

PMID- 23142906
TI  - Work transitions: knowledge synthesis and student reflections.

PMID- 23142907
TI  - Celebrating student reflections on occupational transitions: a Chilean journey.

PMID- 23142908
TI  - The influence of work-life balance, choice and a meaningful location on work
      transitions.
AB  - OBJECTIVE: To explore career transitions using an occupational perspective.
      PARTICIPANT: One man shared his views on career transitions to elaborate concepts
      on work-life balance, choice and meaning. METHOD: Narrative reflection and
      theoretical exploration of occupational concepts underscoring career transitions.
      RESULTS: Three concepts are important to understanding career transitions, work
      life balance, making meaning choices, and place. CONCLUSIONS: Further development
      in work transitions can be elaborated using an occupational understanding.

PMID- 23142909
TI  - Occupational transitions: restructuring a life.
AB  - OBJECTIVE: This personal reflection on occupational transitions is based on the
      life stories of two of the interesting people I met while in Chile, one in
      Santiago and the other in my travels to San Pedro de Atacama and how their
      stories have aided in strengthening my knowledge of occupational transitions.
      PARTICIPANTS: Purposeful restructuring of one's life is key to developing
      identity and meaningful engagement in daily and occupational life. METHODS: Both
      Mauricio and Francisco share, through their occupational transition self
      narratives, how they restructured their lives by finding out who they really
      were, as well as what was most important to them. RESULTS: I believe that the
      consistent theme or catalyst of change within these stories is one of being
      unsatisfied with a current situation and as a result, making a conscious decision
      to recreate/restructure one's identity and sense of being. CONCLUSIONS: When
      seeking to both understand and apply a term like occupational transition, it will
      be important to not preclude the individual human stories, both told and untold,
      that will enable a more complete and compassionate understanding of occupational
      transitions for both researchers and clinicians.

PMID- 23142910
TI  - From paid work to volunteerism during one case of natural disaster: interacting
      micro and macro level transitions.
AB  - OBJECTIVE: To examine micro and macro influences on transitions from paid work to
      volunteerism. PARTICIPANTS: Narrative life stories from the people of Chile after
      a natural disaster. METHOD: Personal reflection on lived experiences in work
      transitions and theoretical concepts in occupational transitions. RESULT:
      Tensions at the micro and macro levels influence transitions and decisions to
      make significant transitions in work. CONCLUSIONS: Unexpected and unanticipated
      work transitions open the door to personal reflection and in this case an
      individual's sense of perceived inaction on the institutional level directed
      action on the individual level. Thus, confirming suggestion that a dialectical
      relationship of mutual influence exists between micro and macro level
      occupational transitions when unanticipated major life and work transitions
      transpire.

PMID- 23142911
TI  - The 9 to 5 routine: advancing the understanding of occupational transition for
      new immigrants.
AB  - OBJECTIVE: This paper offers a reflection on temporal routines that underscore
      daily work life and work transitions. PARTICIPANTS: This reflection includes
      views of a Canadian student who examines work transitions through lived
      experiences and observation of the Chilean work/home routine. METHOD: A narrative
      reflection on lived experience is used to examine 9 to 5 work transitions.
      RESULTS: There is a blending of work and daily life routines that provide a
      balance for workers in Chile and there are differences across countries in the
      valuing of work and daily life routines. CONCLUSIONS: Narrative reflections about
      work and work transitions can highlight differences at the macro level that can
      yield personal insights into challenges in transitioning into work for new
      immigrants.

PMID- 23142912
TI  - Reflections on gender issues in work transitions in Chile.
AB  - OBJECTIVE: To explore the work transitions of Chilean women. PARTICIPANTS:
      Observations and dialogue of Chilean women and their experiences in current and
      past work. METHOD: A personal and historical reflection to understand the
      experiences of work for Chilean women. RESULTS: Exploring work transitions
      requires an understanding of the macro level historical impact on the
      participation of women in work in Chilean society. CONCLUSIONS: Macro level
      factors such as participation in the free labour market economy ultimately
      impacts on the individual choices of the women of Chile regarding their
      opportunities to transition into productive paid employment. The understanding of
      work transitions must consider the influences of the labour market economy.

PMID- 23142913
TI  - Student reflections on unexpected work transitions due to natural disaster in
      Chile.
AB  - OBJECTIVE: This article presents a reflection on four students' experiences on
      unexpected work transitions due to natural disaster in Chile. PARTICIPANTS:
      Discussions with locals encountered while traveling throughout Chile prompted the
      authors to explore the ideas of occupational identity and global stigma attached
      to unexpected work transitions. METHODS: The authors present here, excerpts from
      reflective journaling and an exploration of factors affecting certain
      individual's ability to adapt and regain occupational identity that has either
      shifted or been lost due to the effects of natural disaster. The authors explore
      both micro and macro level factors that may affect this occupational shift, and
      how attempts to maintain occupation after natural disaster is influenced not only
      by person factors, but largely by global perceptions of the country affected by
      natural disaster. RESULTS AND CONCLUSIONS: Lastly, the authors reflect on this
      experience from a student perspective, the impact it has on emerging occupational
      therapists, and the need for more focused research concerning global stigma and
      its cascading effects.

PMID- 23142914
TI  - Unforgotten to the unforgettable: how Arpilleras contributed to Chilean history
      informing everyday occupations and social change.
AB  - OBJECTIVE: The September 11, 1973 Pinochet military coup marks the anniversary of
      a changed way of life for everyone in Chile and has influenced people around the
      world. This paper provides a reflection on the social, political, and personal
      injustices faced by the women of Chile during a vicious dictatorship, through the
      depiction of an Arpillera. PARTICIPANTS: This paper unfolds the women's
      experience of occupational transitions and how they shared their stories of
      injustices to the world at a time when almost all other voices of protest had
      been silenced. METHOD: A narrative and historical reflection is used to offer an
      interpretation of the experiences of transitions among these women. CONCLUSION:
      Through the art of survival and a shared mission, the women of Chile worked
      outside of the traditional political system to effect political change.

PMID- 23142915
TI  - A scoping review on occupational and self identity after a brain injury.
AB  - OBJECTIVE: Persons with brain injury experience a shift in their self identity
      that is underpinned by work loss and changes to their worker role. However,
      little is known on how to assist a worker with a brain injury re-establish their
      occupational identity. Thus, the objective of this article is to present the
      results of a scoping review undertaken to examine the literature on occupational
      identity and self identity after a brain injury. METHODS: A scoping review was
      performed using the keywords traumatic, acquired brain injury, occupational, and
      self identity. Articles were narrowed through three phases which involved
      reviewing articles to ensure a thorough discussion of identity after a brain
      injury was included and to highlight the research questions. RESULTS: In total 16
      articles and 3 theses were included. No articles were retrieved on occupational
      identity after a brain injury. Fourteen articles discussed the loss of self
      identity experienced after a brain injury while three articles highlighted
      rehabilitation programs. CONCLUSIONS: Research indicates there are extensive
      changes to identity after a brain injury and this impacts returning to previous
      occupations. This knowledge can further our understanding of returning to
      occupations after a brain injury and the impact on occupational identity.

PMID- 23142916
TI  - Seasonal transitions and social responsibility.
AB  - OBJECTIVE: This paper is a reflection on work transitions in an international
      context. PARTICIPANTS: Seasonal employees and employer of the winery Emiliana.
      METHODS: The following is a personal reflection by a Canadian occupational
      therapy student after a recent trip to Chile. RESULTS AND CONCLUSIONS: The
      commitment to social responsibility by the winery Emiliana guided the reflection
      on work transitions of seasonal employees and the employer's provision of
      services to improve employee's quality of life.

PMID- 23142917
TI  - Work capacity assessment and return to work: a scoping review.
AB  - OBJECTIVE: This review sought to synthesize existing evidence on work capacity
      assessments and to identify the knowledge supporting their use in return to work
      practice and future research. METHODS: A scoping review was conducted identifying
      studies examining assessments used in return to work. Studies published before
      1986 and studies not written in English were excluded. A five point relevancy
      criteria was used to establish the fit of articles with the research question.
      Articles were thematically analyzed into components of the PEO Model, proposed
      future research, and areas of vested interest. RESULTS: Forty four articles met
      the criteria for inclusion. For over twenty five years, work capacity assessment
      literature has remained focused on the individual's physical work performance
      capacities. Gaps were identified in the lack of qualitative research and
      incorporation of person, occupation, and environmental dimensions in evaluation
      of work capacity. Future research recommendations emphasize the need for
      knowledge generation on work modification and investigation of psychosocial
      factors that impact work capacity and return to work yet only minimal progression
      is evident in these areas in the literature reviewed. CONCLUSION: The limited
      consideration of the occupation and environmental dimensions in returning to work
      and the global interest in work capacity assessment highlight the need for the
      development of contextually based assessment tools. Assessment needs to move
      toward the incorporation of environmental and occupational aspects in addition to
      the person dimension in a culturally transcendent manner.

PMID- 23142918
TI  - Chronic pain in episodic illness and its influence on work occupations: a scoping
      review.
AB  - OBJECTIVES: The aim of this review was to understand and synthesize the realm of
      knowledge on intermittent work capacity (IWC) about strategies to support work
      sustainability. Specifically, this review focused on literature that examined
      productive work with individuals who have chronic pain due to Fibromyalgia,
      Breast Cancer, Multiple Sclerosis, and Human Immunodeficiency Virus. METHODS: A
      scoping review of research conducted across 10 databases. Nature of the knowledge
      base on return to work barriers and strategies and future recommended strategies
      needed to support persons with IWC in maintaining work participation were charted
      and thematically analyzed and organized into micro, meso and macro categories.
      RESULTS: Majority of the knowledge base reflects factors impeding and
      facilitating employment or re-employment at the micro level. At the micro level,
      self advocacy was a strategy that persons with IWC used to maintain employment
      and navigate stigmatizing work environments to meet their needs. At the meso
      level education and knowledge sharing with employers to increase awareness was
      underscored; at the macro level introduction of new policies was recommended.
      CONCLUSIONS: These findings suggest the need for future greater examination of
      the dialectical relationships across micro, meso and macro level strategies to
      overcome work disparities for persons with IWC.

PMID- 23142919
TI  - Model for prioritizing best management practice implementation: sediment load
      reduction.
AB  - Understanding the best way to allocate limited resources is a constant challenge
      for water quality improvement efforts. The synoptic approach is a tool for
      geographic prioritization of these efforts. It uses a benefit-cost framework to
      calculate indices for functional criteria in subunits (watersheds, counties) of a
      region and then rank the subunits. The synoptic approach was specifically
      designed to incorporate best professional judgment in cases where information and
      resources are limited. To date, the synoptic approach has been applied primarily
      to local or regional wetland restoration prioritization projects. The goal of
      this work was to develop a synoptic model for prioritizing watersheds within
      which suites of agricultural best management practices (BMPs) can be implemented
      to reduce sediment load at the watershed outlets. The model ranks candidate
      watersheds within an ecoregion or river basin so that BMP implementation within
      the highest ranked watersheds will result in the most sediment load reduction per
      conservation dollar invested. The model can be applied anywhere and at many
      scales provided that the selected suite of BMPs is appropriate for the evaluation
      area's biophysical and climatic conditions. The model was specifically developed
      as a tool for prioritizing BMP implementation efforts in ecoregions containing
      watersheds associated with the USDA-NRCS conservation effects assessment project
      (CEAP). This paper presents the testing of the model in the little river
      experimental watershed (LREW) which is located near Tifton, Georgia, USA and is
      the CEAP watershed representing the southeastern coastal plain. The application
      of the model to the LREW demonstrated that the model represents the physical
      drivers of erosion and sediment loading well. The application also showed that
      the model is quite responsive to social and economic drivers and is, therefore,
      best applied at a scale large enough to ensure differences in social and economic
      drivers across the candidate watersheds. The prioritization model will be used
      for planning purposes. Its results are visualized as maps which enable resource
      managers to identify watersheds within which BMP implementation would result in
      the most water quality improvement per conservation dollar invested.

PMID- 23142920
TI  - Impact of learning curve and technical changes on dosimetry in low-dose
      brachytherapy for prostate cancer.
AB  - PURPOSE: To assess the impact of experience and technical changes on peri- and
      postimplantation (1 month later) dosimetry for permanent prostate brachytherapy
      (PPB). PATIENTS AND METHODS: From July 2003 to May 2010, 150 prostate cancer
      patients underwent low-dose, loose-seed I(125) PPB as monotherapy with
      intraoperative planning. Patients were divided into three groups-P1 (n = 64), P2
      (n = 45), P3 (n = 41)-according to the technical changes that occurred during the
      study period: use of an automatic stepper at the beginning of P2 and a high
      frequency ultrasound probe in P3. Peri- and postimplantation dosimetric
      parameters (on day 30) were reported: D90 (dose received by 90% of prostate
      volume), V100 and V150 (prostate volume receiving, respectively, 100% and 150% of
      the prescribed dose), D2 cc and D0.1 cc (doses received by 2 cc and 0.1 cc of the
      rectum), R100 (rectum volume that received 100% of the prescribed dose), and D10
      and D30 (doses received by 10% and 30% of the urethra, only during peri
      implantation). RESULTS: We observed a decrease in the number of needles and seeds
      used over time. The mean peri-implantation D90 was 187.52 Gy without a
      significant difference between the three periods (p = 0.48). The postimplantation
      D90, V100, and V150 parameters were, respectively, 168.3 Gy, 91.9%, and 55% with
      no significant difference between the three periods. The peri-implantation and
      postimplantation D0.1 cc and R100 significantly decreased over time; on day 30:
      D0.1 cc P1 = 223.1 Gy vs. D0.1 cc P3 = 190.4 Gy (p = 8.10(-5)) and R100 P1 = 1.06
      cc vs. R100 P3 = 0.53 cc (p = 0.0008). CONCLUSION: We observed a learning curve
      for the implantation parameters, which led to a significant decrease in the
      rectal doses without having any impact on the prostate dosimetric parameters.

PMID- 23142921
TI  - [Radiation therapy in patients with cardiac pacemakers or implantable
      cardioverter defibrillators. Interdisciplinary safety recommendations].
AB  - BACKGROUND: With increasing numbers of implanted pacemakers and implantable
      cardioverter defibrillators (ICD) and a rising incidence of malignant tumors,
      there is a growing probability of radiation-mediated device dysfunction. The only
      guidelines for the management of patients with cardiac pacemakers in the case of
      radiation therapy were published in 1994 and have not been updated since then.
      Based on the current evidence and modern device technology, the present paper
      aims to develop contemporary and interdisciplinary safety recommendations for the
      minimization of patient risk. METHODS AND RESULTS: A systematic literature
      research was carried out including the most relevant medical electronic
      databases. The search yielded 147 articles published between 1994 and 2012 of
      which 45 met the selection criteria and of these studies 34 presented primary
      data (9 in vitro and 25 in vivo studies). The impact of ionizing radiation varied
      significantly between implanted devices and ranged from no functional changes to
      complete loss of function. Important device dysfunctions included changes in
      sensing capability, altered pacing pulses or rate, changed or disabled
      tachyarrhythmia ICD therapies, early battery depletion and loss of telemetry.
      Modern pacemakers and ICDs are more sensitive to radiation than older models.
      Potentially life-threatening complications were observed after exposure of the
      pulse generator to comparatively low radiation doses (0.11 Gy). CONCLUSIONS:
      Practical recommendations for patient management and safety are presented that
      can be readily adopted by any institution carrying out radiation therapy.

PMID- 23142922
TI  - [Results of a randomized phase III study on treatment of recurrent glioblastoma:
      NovoTTF-100A versus chemotherapy].

PMID- 23142923
TI  - Reply to: adherence to recommendation for chemotherapy-induced nausea and
      vomiting prophylaxis: the proposal of a score.

PMID- 23142925
TI  - The Australian baby boomer population--factors influencing changes to health
      related quality of life over time.
AB  - OBJECTIVE: Identify factors associated with changes to health-related quality of
      life (HRQoL) in baby boomers. METHODS: Panel data were collected on baby boomers
      at two time points, 2000-2002 and 2004-2006. A fixed-effects model was used to
      identify associations between changes in the dependent variable (SF-36 summary
      scales) and changes in independent variables (health indicators/employment
      status). RESULTS: Mental health problems, being out of labor force, sedentary
      behavior, and severe lung disease were associated with deterioration in physical
      and mental HRQoL. Obesity was associated with deterioration in physical HRQoL
      whereas cardiovascular disease was associated with deterioration in mental HRQoL.
      Unemployment, full-time employment, and absence of lung disease symptoms were
      associated with improvements in physical and mental HRQoL. DISCUSSION: If we are
      to maximize the future labor participation, and HRQoL, of this cohort, it will be
      necessary to reduce obesity and sedentary behavior and to further investigate the
      association between health and employment.

PMID- 23142924
TI  - Systematic review of agents for the management of gastrointestinal mucositis in
      cancer patients.
AB  - PURPOSE: The aim of this study was to review the available literature and define
      clinical practice guidelines for the use of agents for the prevention and
      treatment of gastrointestinal mucositis. METHODS: A systematic review was
      conducted by the Mucositis Study Group of the Multinational Association of
      Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO).
      The body of evidence for each intervention, in each cancer treatment setting, was
      assigned an evidence level. Based on the evidence level, one of the following
      three guideline determinations was possible: recommendation, suggestion, and no
      guideline possible. RESULTS: A total of 251 clinical studies across 29
      interventions were examined. Panel members were able to make one new evidence
      based negative recommendation; two new evidence-based suggestions, and one
      evidence-based change from previous guidelines. Firstly, the panel recommends
      against the use of misoprostol suppositories for the prevention of acute
      radiation-induced proctitis. Secondly, the panel suggests probiotic treatment
      containing Lactobacillus spp., may be beneficial for prevention of chemotherapy
      and radiotherapy-induced diarrhea in patients with malignancies of the pelvic
      region. Thirdly, the panel suggests the use of hyperbaric oxygen as an effective
      means in treating radiation-induced proctitis. Finally, new evidence has emerged
      which is in conflict with our previous guideline surrounding the use of systemic
      glutamine, meaning that the panel is unable to form a guideline. No guideline was
      possible for any other agent, due to inadequate and/or conflicting evidence.
      CONCLUSIONS: This updated review of the literature has allowed new
      recommendations and suggestions for clinical practice to be reached. This
      highlights the importance of regular updates.

PMID- 23142926
TI  - Differential expression of Na+, K(+)-ATPase alpha-1 isoforms during seawater
      acclimation in the amphidromous galaxiid fish Galaxias maculatus.
AB  - Inanga (Galaxias maculatus) is an amphidromous fish with a well-known capacity to
      withstand a wide range of environmental salinities. To investigate the molecular
      mechanisms facilitating acclimation of inanga to seawater, several isoforms of
      the Na(+), K(+)-ATPase ion transporter were identified. This included three alpha
      1 (a, b and c), an alpha-2 and two alpha-3 (a and b) isoforms. Phylogenetic
      analysis showed that the inanga alpha-1a and alpha-1b formed a clade with the
      alpha-1a and alpha-1b isoforms of rainbow trout, while another clade contained
      the alpha-1c isoforms of these species. The expression of all the alpha-1
      isoforms was modulated after seawater exposure (280/00). In gills, the expression
      of the alpha-1a isoform was progressively down-regulated after seawater exposure,
      while the expression of the alpha-1b isoform was up-regulated. The alpha-1c
      isoform behaved similarly to the alpha-1a, although changes were less dramatic.
      Physiological indicators of salinity acclimation matched the time frame of the
      changes observed at the molecular level. A 24-h osmotic shock period was
      highlighted by small increases in plasma osmolality, plasma Na(+) and a decrease
      in muscle tissue water content. Thereafter, these values returned close to their
      pre-exposure (freshwater) values. Na(+), K(+)-ATPase activity showed a decreasing
      trend over the first 72 h following seawater exposure, but activity increased
      after 240 h. Our results indicate that inanga is an excellent osmoregulator, an
      ability that is conferred by the rapid activation of physiological and molecular
      responses to salinity change.

PMID- 23142927
TI  - Performance of planar and cylindrical carbon electrodes at sedimentary microbial
      fuel cells.
AB  - This paper presents data obtained using an indigenous microbial community
      contained in anaerobic sediments (mud) collected from the shore of the Rio de La
      Plata River (South America). After the sedimentary microbial fuel cells were
      assembled the evolution of current and power vs. time was studied. Two types of
      commercially available graphite materials were used as electrodes, which differ
      mainly in shape and size. In some experiments, an external carbon source
      (acetate) increased the power generation rate. The maximum power density observed
      in the aforementioned condition was 19.57 +/- 0.35 and 8.72 +/- 1.39 mW/m(2)
      using rod and graphite disk electrodes, respectively. The better performance of
      the rod electrodes can be explained, at least in part, by an enhanced rate of
      mass transport by radial diffusion. DGGE fingerprints were used to study the
      electrogenic community growing over the electrodes.

PMID- 23142928
TI  - Extended graphynes: simple scaling laws for stiffness, strength and fracture.
AB  - The mono-atomistic structure and chemical stability of graphene provides a
      promising platform to design a host of novel graphene-like materials. Using full
      atomistic first-principles based ReaxFF molecular dynamics, here we perform a
      systematic comparative study of the stability, structural and mechanical
      properties of graphynes - a variation of the sp(2) carbon motif wherein the
      characteristic hexagons of graphene are linked by sp(1) acetylene (single- and
      triple-bond) carbyne-like chains. The introduction of acetylene links introduces
      an effective penalty in terms of stability, elastic modulus (i.e., stiffness),
      and failure strength, which can be predicted as a function of acetylene repeats,
      or, equivalently, lattice spacing. We quantify the mechanical properties of
      experimental accessible graphdiyne, with a modulus on the order of 470 to 580 GPa
      and a ultimate strength on the order of 36 GPa to 46 GPa (direction dependent).
      We derive general scaling laws for the cumulative effects of additional acetylene
      repeats, formulated through a simple discrete spring-network framework, allowing
      extrapolation of mechanical performance to highly extended graphyne structures.
      Onset of local tensile buckling results in a transitional regime characterized by
      a severe reduction of strength (ultimate stress), providing a new basis for
      scaling extended structures. Simple fracture simulations support the scaling
      functions, while uncovering a "two-tier" failure mode for extended graphynes,
      wherein structural realignment facilitates stress transfer beyond initial
      failure. Finally, the specific modulus and strength (normalized by areal density)
      is found to be near-constant, suggesting applications for light-weight, yet
      structurally robust molecular components.

PMID- 23142929
TI  - Identification of a MHC I-restricted epitope of DsRed in C57BL/6 mice.
AB  - Fluorescent proteins can be used to visualize cells and their constituents by
      various imaging techniques. Adoptive transfer of T cells from C57Bl/6 (B6) mice
      that expressed DsRed.T3 under the actin promoter lead to frequent rejection of
      transferred cells. In short term in vivo cytotoxicity assays these mice showed
      detectable, but weak lysis of DsRed spleen cells but their responses could be
      boosted by re-challenge with DsRed spleen cells. To determine whether DsRed
      protein may contain an H-2(b) MHC I-restricted T cell epitope, B6 mice immune to
      DsRed spleen cells were examined for in vivo lysis of target cells coated with
      various DsRed-derived peptides selected by the SYFPEITHI epitope prediction
      program. This analysis identified one D(b)-restricted peptide sequence within
      DsRed (SSLQDGCFI) that acted as an epitope for B6 target lysis. Knowledge of this
      epitope could allow DsRed to be used as a model antigen in B6 mice and cautions
      against using this fluorochrome, as well as several others containing the
      immunogenic sequence, in adoptive transfer studies where rejection is not
      desirable.

PMID- 23142930
TI  - Neuropeptides isotocin and arginine vasotocin in urophysis of three fish species.
AB  - In this study, for the first time, both neuropeptides isotocin (IT) and arginine
      vasotocin (AVT) have been identified and measured in urophysis, the neurohaemal
      organ of the caudal neurosecretory system of teleost fish. So far, AVT, but not
      IT, was quantified by radioimmunoassay (RIA) in urophysis of several fish
      species. We have used high-performance liquid chromatographic assay with
      fluorescence detection (HPLC-FL) preceded by solid-phase extraction (SPE) and
      liquid chromatography-electrospray ionization triple-quadrupole tandem mass
      spectrometry (LC-ESI MS/MS) technique to determine both neuropeptides in
      urophysis of three fish species. The efficiency of peptide's SPE extraction was
      79-85%. In HPLC-FL method, the limits of detection (LOD) and quantification (LOQ)
      were estimated as 1.0 and 3.4 pmol/mL for IT and 0.25 and 2.20 pmol/mL for AVT.
      In LC-MS/MS method, LOD and LOQ were estimated as 0.4 and 1.2 pmol/mL for IT and
      0.06 and 0.2 pmol/mL for AVT. The chromatographic methods are good alternative
      for RIA, because enable to measure both nonapeptides simultaneously in one
      sample. In round goby (Neogobius melanostomus), three-spined stickleback
      (Gasterosteus aculeatus) and sea bream (Sparus aurata), urophysial IT
      concentrations ranged between 0.056 and 0.678 pmol/mg tissue and AVT
      concentrations ranged between 0.0008 (or even below detection threshold) and
      0.084 pmol/mg tissue.

PMID- 23142931
TI  - Ultraviolet light and photodynamic therapy induce apoptosis in nasal polyps.
AB  - Intranasal phototherapy has been found to be effective for the treatment of nasal
      polyposis (NP) therefore the aim was to investigate the apoptosis inducing effect
      of phototherapy in NP. In this ex vivo study nasal polyp tissue was surgically
      collected from 21 consecutive patients with chronic rhinosinusitis (CRS)
      associated with NP. The removed polyps were cut into pieces and tissue samples
      were irradiated in vitro by different doses of combined ultraviolet and visible
      light (UV/VIS: 280-650 nm) and by selective ultraviolet and visible light
      (sUV/VIS: 295-650 nm). Photodynamic therapy (PDT) was performed by presensitizing
      tissue samples with 5-delta-aminolevulinic acid (DALA) then irradiated with
      visible light (VIS: 395-650 nm). Tunel assay was applied to detect apoptosis of
      epithelial and inflammatory cells in irradiated and control nasal polyp tissue
      samples. UV/VIS light significantly increased epithelial cell and subepithelial
      leukocyte apoptosis compared to control groups. PDT treatment showed the highest
      surface epithelial cell as well as subepithelial leukocyte apoptosis compared to
      all other groups. Intranasal phototherapy may serve as a new potential
      therapeutical method in treatment of NP.

PMID- 23142932
TI  - Saponins from Tribulus terrestris L. protect human keratinocytes from UVB-induced
      damage.
AB  - Chronic exposure to solar UVB radiation damages skin, increasing the risk to
      develop cancer. Hence the identification of compounds with a photoprotective
      efficacy is essential. This study examined the role of saponins derived from
      Tribulus terrestris L. (TT) on the modulation of apoptosis in normal human
      keratinocytes (NHEK) exposed to physiological doses of UVB and to evaluate their
      antitumoral properties. In NHEK, TT saponins attenuate UVB-induced programmed
      cell death through inhibition of intrinsic apoptotic pathway. In squamous cell
      carcinomas (SCC) TT saponins do not make the malignant keratinocytes more
      resistant to UVB and determine an enhanced apoptotic response. The
      photoprotective effect of TT saponins is tightly correlated to the enhancement of
      NER genes expression and the block of UVB-mediated NF-kappaB activation.
      Collectively, our study shows experimental evidence that TT has a preventive
      efficacy against UVB-induced carcinogenesis and the molecular knowledge on the
      mechanisms through which TT saponins regulate cell death suggests great potential
      for TT to be developed into a new medicine for cancer patients.

PMID- 23142933
TI  - Production of hydrogen peroxide and hydroxyl radical in potato tuber during the
      necrotrophic phase of hemibiotrophic pathogen Phytophthora infestans infection.
AB  - In this study, evidence is provided on the formation of hydrogen peroxide
      (H(2)O(2)) and hydroxyl radical (HO) in the potato tuber during the necrotrophic
      phase of the hemibiotrophic pathogen Phytophthora infestans infection. Using 3,3
      diaminobenzidine tetrahydrochloride (DAB) imaging technique, the formation of
      H(2)O(2) was demonstrated in P. infestans-infected potato tuber. For the first
      time, HO formation was demonstrated in P. infestans-infected potato tuber using
      electron paramagnetic resonance (EPR) spectroscopy. An enhancement in spontaneous
      ultra-weak photon emission indicated the extent of lipid peroxidation in the P.
      infestans-infected potato tuber. The data presented in this study reveal that the
      formation of H(2)O(2) and HO in the P. infestans-infected potato tuber is
      associated with lipid peroxidation. It is proposed here that the ultra-weak
      photon emission can be used as a non-invasive indicator of the oxidative
      processes in the quality control at food industry.

PMID- 23142934
TI  - So you want to become a plastic surgeon? What you need to do and know to get into
      a plastic surgery residency.

PMID- 23142936
TI  - Patient-reported satisfaction and health-related quality of life following breast
      reconstruction: a comparison of shaped cohesive gel and round cohesive gel
      implant recipients.
AB  - BACKGROUND: Decision-making in breast reconstruction is complicated as women are
      offered an increasingly large range of options. Alloplastic surgery continues to
      evolve with the introduction of new prostheses to the breast reconstruction
      market but with limited patient-reported outcomes data. Evaluating the outcomes
      of surgical interventions and their impact on patients is imperative to improve
      the patient decision-making process and to improve quality of care. The authors
      evaluated the effect of the two most commonly used silicone prostheses on patient
      reported satisfaction and health-related quality of life following alloplastic
      breast reconstruction. METHODS: Patients were deemed eligible if they had
      completed alloplastic reconstruction at least 1 year before study initiation.
      Patients were contacted by mail with the BREAST-Q questionnaire, a contact
      letter, and an incentive gift card. BREAST-Q scores were compared between shaped
      cohesive and round cohesive silicone gel implant recipients. RESULTS: Sixty-five
      round, cohesive, non-form-stable and 63 shaped, cohesive, form-stable silicone
      gel implant recipients responded, for an overall response rate of 75 percent.
      BREAST-Q responses showed no difference on any scale, including overall
      satisfaction with breast and outcome. Item-wise analysis revealed that implant
      recipients find shaped cohesive form-stable implants to be significantly firmer
      than cohesive round implants. No difference was found in implant rippling.
      CONCLUSION: Although previous studies have shown silicone implant recipients to
      be more satisfied overall than saline implant recipients after alloplastic breast
      reconstruction, this study showed that patients do not differ in terms of
      satisfaction with outcome when compared regarding reconstruction using round
      versus shaped cohesive silicone gel implants.

PMID- 23142937
TI  - Autologous fat grafting and injectable dermal fillers for human immunodeficiency
      virus-associated facial lipodystrophy: a comparison of safety, efficacy, and long
      term treatment outcomes.
AB  - BACKGROUND: Facial lipoatrophy is a common side effect of human immunodeficiency
      virus treatment with highly active antiretroviral therapy. To identify the most
      clinically durable and efficient way of addressing facial lipoatrophy, the
      authors reviewed all available evidence for the use of injectable dermal fillers
      and autologous fat transfers as treatment modalities, focusing on safety,
      outcomes, and long-term durability. METHODS: A systematic review of the Cochrane
      and MEDLINE databases for autologous fat transfer and injectable dermal fillers
      for the treatment of human immunodeficiency virus-associated lipodystrophy was
      performed. Based on U.S. Food and Drug Administration approval in human
      immunodeficiency virus lipoatrophy, studies were limited to the use of hyaluronic
      acid and/or poly-L-lactic acid. Facial volume, subjective patient satisfaction,
      standardized outcome scales, reinjection rates, and complications were recorded.
      RESULTS: Nineteen studies were included representing 724 patients, with 549
      patients in the hyaluronic acid/poly-L-lactic acid cohort and 175 in the
      autologous fat transfer cohort. Improvements in facial volume and durability of
      treatment were similar between dermal fillers and fat transfer, as measured by
      both objective means and subjective patient outcomes. However, poly-L-lactic acid
      was reinjected at a rate three times that of autologous fat, and was associated
      with a relatively high rate of subcutaneous papule formation at 22 percent
      (range, 3 to 44 percent). CONCLUSIONS: Dermal fillers and autologous fat transfer
      are effective treatment modalities for human immunodeficiency virus-associated
      facial lipoatrophy, with high rates of facial volume restoration and patient
      satisfaction. Autologous fat transfer may offer similar to superior long-term
      durability but with less of a financial burden compared with injectable fillers.

PMID- 23142938
TI  - Transdiaphragmatic omental harvest: a simple, efficient method for sternal wound
      coverage.
AB  - BACKGROUND: The greater omentum is easily harvested for coverage of sternal
      wounds without muscle sacrifice. Its major disadvantage is a laparotomy incision
      with potential bowel injury, adhesions, or hernia. Over the past 20 years, the
      authors' technique has evolved to use a transdiaphragmatic opening for omental
      harvest when possible. METHODS: The authors performed a retrospective cohort
      analysis of 140 consecutive patients undergoing omental flap harvest for
      treatment of sternal wounds following median sternotomy. Patients were divided
      into two groups by access incision: laparotomy incision (n = 80) versus a
      transdiaphragmatic opening (n = 60). RESULTS: The authors found that both
      techniques provided reliable closure of sternal wounds, but the
      transdiaphragmatic approach was faster, with less blood loss. There was no
      significant difference in rates of ventral hernias. We had only one bowel injury
      (laparotomy group) and no postoperative abdominal bleeding or small bowel
      obstruction. CONCLUSION: Transdiaphragmatic omental harvest provides safe and
      efficient coverage of deep sternal wounds without a laparotomy incision.

PMID- 23142939
TI  - An algorithmic approach to the management of limb ischemia in infants and young
      children.
AB  - BACKGROUND: Vascular injuries in newborns are rare and most commonly occur in the
      process of obtaining vascular access for monitoring organ system functions or
      interventions in critical care. Care of vascular injuries in neonates poses
      several challenges, with the most significant arguably being the lack of clinical
      experience with such injuries. An algorithm for the management of arterial
      injuries in pediatric patients is investigated and reported. METHODS: A
      retrospective chart analysis was performed on all patients consulted for the
      management of vascular injury by the plastic surgery service at Texas Children's
      Hospital between 1997 and 2005. The outcomes and procedures were reviewed.
      RESULTS: Thirty vascular insults in 28 patients were evaluated and treated by the
      senior author (J.D.F.) using this protocol. Thirty-seven percent (11 of 30) were
      approached surgically, including two cases treated with thrombolysis alone. The
      remaining 63 percent (19 of 30) were managed with more conservative
      interventions, including anticoagulation and clinical optimization. When color
      Doppler imaging was used preoperatively to locate and describe the
      characteristics of vascular injuries, visualized lesions coincided with the
      surgical findings in 100 percent (11 of 11 cases). Twenty-three limbs (77
      percent) were salvaged completely using this algorithm, one was initially
      salvaged but later developed limb-length discrepancy requiring amputation, and
      one experienced complete limb loss. The remaining patients (five of 30) died as a
      result of complications of their primary medical conditions before limb salvage
      could be assessed. CONCLUSION: This evaluation demonstrates the efficacy of the
      proposed algorithm used to determine direction of care in the event of arterial
      injury in small children.

PMID- 23142940
TI  - The influence of procedure delay on resource use: a national study of patients
      with open tibial fracture.
AB  - BACKGROUND: The purpose of this study was to (1) understand national variation in
      delay of emergency procedures in patients with open tibial fracture at the
      hospital level and (2) compare length of stay and cost in patients cared for at
      the best- and worst-performing hospitals for delay. METHODS: The authors
      retrospectively analyzed the 2003 to 2009 Nationwide Inpatient Sample. Adult
      patients with open tibial fracture were included. Hospital probability of delay
      in performing emergency procedures beyond the day of admission was calculated.
      Multilevel linear regression random-effects models were created to evaluate the
      relationship between the treating hospital's tendency for delay (in quartiles)
      and the log-transformed outcomes of length of stay and cost. RESULTS: The final
      sample included 7029 patients from 332 hospitals. Patients treated at hospitals
      in the fourth (worst) quartile for delay were estimated to have 12 percent (95
      percent CI, 2 to 21 percent) higher cost compared with patients treated at
      hospitals in the first quartile. In addition, patients treated at hospitals in
      the fourth quartile had an estimated 11 percent (95 percent CI, 4 to 17 percent)
      longer length of stay compared with patients treated at hospitals in the first
      quartile. CONCLUSIONS: Patients with open tibial fracture treated at hospitals
      with more timely initiation of surgical care had lower cost and shorter length of
      stay than patients treated at hospitals with less timely initiation of care.
      Policies directed toward mitigating variation in care may reduce unnecessary
      waste.

PMID- 23142941
TI  - Propranolol versus corticosteroids in the treatment of infantile hemangioma: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Infantile hemangiomas are benign vascular neoplasms that can cause
      numerous functional or cosmetic problems. The authors reviewed the pathogenesis
      of hemangioma and compared the efficacy and complications related to therapy with
      propranolol versus corticosteroids. METHODS: A comprehensive review of the
      literature was conducted from 1965 to March of 2012 using MEDLINE, PubMed, Ovid,
      Cochrane Review database, and Google Scholar. All articles were reviewed for
      reports of clinical cases, reported side effects, doses, duration of treatment,
      number of patients, and response rate to treatment. RESULTS: A total of 1162
      studies were identified. Of those, only 56 articles met inclusion criteria after
      review by two independent reviewers (A.I. and J.K.). For the meta-analysis, 16
      studies comprising 2629 patients and 25 studies comprising 795 patients were
      included. Less than 90 percent of patients treated with corticosteroids responded
      to therapy, compared with 99 percent of patients treated with propranolol after
      12 months of follow-up. Meta-analysis demonstrated the corticosteroid studies to
      have a pooled response rate of 69 percent versus the propranolol response rate of
      97 percent (p < 0.001). CONCLUSIONS: Propranolol is a relatively recent therapy
      of hemangiomas with fewer side effects, a different mechanism of action, and
      greater efficacy than current first-line corticosteroid therapy. Many of these
      studies do not have the same patient population or duration/regimen of treatment
      for hemangiomas; however, based on available data in the literature, it appears
      that propranolol could be an emerging and effective treatment for infantile
      hemangiomas. Further randomized controlled trials are recommended.

PMID- 23142942
TI  - A 20-year experience with secondary rhytidectomy: a review of technique,
      longevity, and outcomes.
AB  - BACKGROUND: The increasingly more common secondary rhytidectomy patient presents
      with recurrent soft-tissue descent and stigmata of primary face lift, which can
      require techniques unique to secondary rhytidectomy. The senior author's (R.J.R.)
      experience with secondary rhytidectomy is reviewed, focusing on surgical
      technique, longevity, and outcomes. METHODS: Data collected after chart review of
      a 20-year study period included face-lift technique; duration between primary,
      secondary, and tertiary face lifts; concurrent procedures; and complications
      (i.e., hematoma, seroma, nerve injury, skin slough, infection, and need for
      revision). Surgical technique focuses on the "five Rs" of secondary rhytidectomy:
      (1) resect skin/scar, (2) release of abnormal superficial musculoaponeurotic
      system (SMAS) vectors, (3) refill by means of fat grafting, (4) reshape with
      SMASectomy or SMAS-stacking plication, and (5) redrape skin. The longevity of
      primary and secondary procedures was compared. RESULTS: A total of 811 face lifts
      were performed during the study period; 60 were secondary procedures. Ten
      secondary patients went on to have a tertiary face lift. Average duration between
      primary and secondary face lift was 9.0 years, and that between secondary and
      tertiary procedures was 7.5 years, showing no difference in longevity (p = 0.2).
      Complications included one each of seroma, skin slough, and temporary marginal
      mandibular nerve injury (2 percent). Necessary revisions included one neck, one
      earlobe, and one preauricular scar. CONCLUSIONS: Secondary rhytidectomy has
      complications similar to those of a primary procedure, and most patients have a
      second operation a decade later. Adherence to the five Rs of secondary
      rhytidectomy will enable the plastic surgeon to safely restore youth and correct
      stigmata of primary face lift.

PMID- 23142943
TI  - Clinical and histopathological study of Charcot-Marie-Tooth neuropathy with a
      novel S90W mutation in BSCL2.
AB  - The objective of the study was to investigate the disease-causing mutation in an
      autosomal dominant Charcot-Marie-Tooth disease type 2 family and examine the
      clinical and histopathological evaluation. We enrolled a family of Korean origin
      with axonal Charcot-Marie-Tooth disease neuropathy (FC305; 13 males, six females)
      and applied genome-wide linkage analysis. Whole exome sequencing was performed
      for two patients. In addition, sural nerve biopsies were obtained from two
      patients. Through whole exome sequencing, we identified an average of 20,336
      coding variants from two patients. We also found evidence of linkage mapped to
      chromosome 11p11-11q13.3 (LOD score of 3.6). Among these variants in the linkage
      region, we detected a novel p.S90W mutation in the Berardinelli-Seip congenital
      lipodystrophy 2 (BSCL2) gene, after filtering 31 Korean control exomes. Our
      p.S90W patients had frequent sensory disturbances, pyramidal tract signs, and
      predominant right thenar muscle atrophy in comparison with reported p.S90L
      patients. The phenotypic spectra were wide and demonstrated intrafamilial
      variability. Two patients with different clinical features underwent sural nerve
      biopsies; the myelinated fiber densities were increased slightly in both
      patients, which differed from two previous case reports of BSCL2 mutations
      (p.S90L and p.N88S). This report expands the variability of the clinical spectrum
      associated with the BSCL2 gene and describes the first family with the p.S90W
      mutation.

PMID- 23142944
TI  - An electrically and mechanically self-healing composite with pressure- and
      flexion-sensitive properties for electronic skin applications.
AB  - Pressure sensitivity and mechanical self-healing are two vital functions of the
      human skin. A flexible and electrically conducting material that can sense
      mechanical forces and yet be able to self-heal repeatably can be of use in
      emerging fields such as soft robotics and biomimetic prostheses, but combining
      all these properties together remains a challenging task. Here, we describe a
      composite material composed of a supramolecular organic polymer with embedded
      nickel nanostructured microparticles, which shows mechanical and electrical self
      healing properties at ambient conditions. We also show that our material is
      pressure- and flexion-sensitive, and therefore suitable for electronic skin
      applications. The electrical conductivity can be tuned by varying the amount of
      nickel particles and can reach values as high as 40 S cm(-1). On rupture, the
      initial conductivity is repeatably restored with ~90% efficiency after 15 s
      healing time, and the mechanical properties are completely restored after ~10
      min. The composite resistance varies inversely with applied flexion and tactile
      forces. These results demonstrate that natural skin's repeatable self-healing
      capability can be mimicked in conductive and piezoresistive materials, thus
      potentially expanding the scope of applications of current electronic skin
      systems.

PMID- 23142945
TI  - A nanocomposite ultraviolet photodetector based on interfacial trap-controlled
      charge injection.
AB  - Ultraviolet photodetectors have applications in fields such as medicine,
      communications and defence, and are typically made from single-crystalline
      silicon, silicon carbide or gallium nitride p-n junction photodiodes. However,
      such inorganic photodetectors are unsuitable for certain applications because of
      their high cost and low responsivity (<0.2 A W(-1)). Solution-processed
      photodetectors based on organic materials and/or nanomaterials could be
      significantly cheaper to manufacture, but their performance so far has been
      limited. Here, we show that a solution-processed ultraviolet photodetector with a
      nanocomposite active layer composed of ZnO nanoparticles blended with
      semiconducting polymers can significantly outperform inorganic photodetectors. As
      a result of interfacial trap-controlled charge injection, the photodetector
      transitions from a photodiode with a rectifying Schottky contact in the dark, to
      a photoconductor with an ohmic contact under illumination, and therefore combines
      the low dark current of a photodiode and the high responsivity of a
      photoconductor (~721-1,001 A W(-1)). Under a bias of <10 V, our device provides a
      detectivity of 3.4 * 10(15) Jones at 360 nm at room temperature, which is two to
      three orders of magnitude higher than that of existing inorganic semiconductor
      ultraviolet photodetectors.

PMID- 23142946
TI  - Potassium channels: a review of broadening therapeutic possibilities for
      neurological diseases.
AB  - Potassium (K(+)) channels are encoded by approximately 80 genes in mammals. They
      are expressed in many tissues and have diverse physiological roles. Human K(+)
      channels are divided mainly into calcium (Ca(2+))-activated (K(Ca)), inward
      rectifying (K(IR)), two-pore (K(2P)), and voltage-gated (K(v)) channels. The K(v)
      channels form the largest family, with approximately 40 genes. Owing to their
      involvement in many diseases and their specific expression patterns and
      physiological roles, K(+) channels present an attractive target for the
      development of new therapies. This review summarizes the physiological and
      pathophysiological roles of various potassium channels with respect to their
      therapeutic potential for disorders with a disturbed neuronal excitability such
      as epilepsy, migraine, neuropathic pain, or stroke.

PMID- 23142947
TI  - Novel mutation in the ATM gene in a Malian family with ataxia telangiectasia.

PMID- 23142948
TI  - Association between root resorption incident to orthodontic treatment and
      treatment factors.

PMID- 23142949
TI  - Reply: To PMID 21811005.

PMID- 23142950
TI  - A dynamic analysis of the display of the dentition during speech.
AB  - The aim of this prospective study was to quantify the display of the dentition
      through the soft tissue frame during speech using videography for different age
      groups. Two hundred and sixty-one subjects were initially screened and were
      divided into five groups: group 1 (G1) (15-19 years), G2 (20-29 years), G3 (30-39
      years), G4 (40-49 years), and G5 (>= 50 years). Groups were also made on the
      basis of gender and history of orthodontic treatment. Video equipment was used to
      capture video and each frame was analysed out of which two frames that best
      represented the maximal display of maxillary incisors (MDMI) during speech and
      the widest transverse display of dentition (WTDD) during speech were selected.
      The data obtained was analysed using one-way analyses of variance with Fisher's
      least significant difference post hoc test. MDMI and WTDD were found to be highly
      significant during speech across all age groups (P < 0.05). G1-G3 displayed
      approximately similar levels of maxillary incisor (P > 0.05) but was greater (P <
      0.05) than G4 and G5. The buccal corridor showed significant differences as a
      function of age (P < 0.05). Orthodontic treatment had a significant impact on the
      display of the maxillary incisors (P < 0.05) but not on the buccal corridors (P >
      0.05). Mandibular incisor display was relatively stable across G1-G3, increasing
      only for G4 and G5. It appears that the maximum display of maxillary incisors
      decreases with age and the decline is particularly rapid with increasing age.
      Females tend to display more teeth both in the transverse and vertical
      directions.

PMID- 23142951
TI  - Minimally invasive thyroidectomy (MIT): indications and results.
AB  - AIM: To establish if the indication for different approaches for thyroidectomy
      and the incision length provided by means of pre-operative assessment of gland
      volume and size of nodules resulted in safe and effective outcomes and in any
      notable aesthetic or quality-of-life impact on patients. MATERIALS AND METHODS:
      Ninehundred eightytwo consecutive patients, undergoing total thyroidectomy, were
      enrolled. The thyroid volume and maximal nodule diameter were measured by means
      of ultrasounds. Based on ultrasounds findings, patients were divided into three
      groups: minimally invasive video assisted thyroidectomy (MIVAT), minimally
      invasive thyroidectomy (MIT) and conventional thyroidectomy (CT) groups. The data
      concerning the following parameters were collected: operative time, postoperative
      complications, postoperative pain and cosmetic results. RESULTS: The MIVAT group
      included 179 patients, MIT group included 592 patients and CT group included 211
      patients. Incidence of complications did not differ significantly in each group.
      In MIVAT and MIT group, the perception of postoperative pain was less intense
      than CT group. The patients in the MIVAT (7+/-1.5) and MIT (8+/-2) groups were
      more satisfied with the cosmetic results than those in CT group (5+/-1.3) (p=
      <0.05). CONCLUSIONS: The MIT is a technique totally reproducible, and easily
      convertible to perform surgical procedures in respect of the patient, without
      additional complications, increased costs, and with better aesthetic results.

PMID- 23142952
TI  - The importance of place names in the search for ecosystem-like concepts in
      indigenous societies: an example from the Bolivian Andes.
AB  - This paper aims to deepen the search for ecosystem-like concepts in indigenous
      societies by highlighting the importance of place names used by Quechua
      indigenous farmers from the central Bolivian Andes. Villagers from two
      communities in the Tunari Mountain Range were asked to list, describe, map and
      categorize the places they knew on their community's territory. Results show that
      place names capture spatially explicit units which integrate biotic and abiotic
      nature and humans, and that there is an emphasis on topographic terms,
      highlighting the importance of geodiversity. Farmers' perspectives differ from
      the classical view of ecosystems because they 'humanize' places, considering them
      as living beings with agency. Consequently, they do not make a distinction
      between natural and cultural heritage. Their perspective of the environment is
      that of a personalized, dynamic relationship with the elements of the natural
      world that are perceived as living entities. A practical implication of the
      findings for sustainable development is that since places names make the links
      between people and the elements of the landscape, toponymy is a tool for
      ecosystem management rooted in indigenous knowledge. Because place names refer to
      holistic units linked with people's experience and spatially explicit, they can
      be used as an entry point to implement an intercultural dialogue for more
      sustainable land management.

PMID- 23142953
TI  - CHO glycosylation mutants as potential host cells to produce therapeutic proteins
      with enhanced efficacy.
AB  - CHO glycosylation mutants, pioneered by Stanley and co-workers, have proven to be
      valuable tools in glycobiology and biopharmaceutical research. Here we aim to
      provide a summary of our efforts to isolate industrially applicable CHO
      glycosylation mutants, termed CHO-gmt cells, using cytotoxic lectins and zinc
      finger nuclease technology. The genetic defects in the glycosylation machinery in
      these cells lead to the production of recombinant glycoproteins with consistent
      and unique glycan structures. In addition, these mutant cells can be easily
      adapted to serum-free medium in suspension cultures, the condition used by the
      biotech industry for large-scale production of recombinant therapeutics. In light
      of the critical impact of glycosylation on biopharmaceutical performances,
      namely, safety and efficacy, the CHO-gmt lines have enormous potential in
      producing glycoprotein therapeutics with optimal glycosylation profiles, thus,
      representing a panel of ideal host cell lines for producing recombinant
      biopharmaceuticals with improved safety profiles and enhanced efficacy.

PMID- 23142954
TI  - Copeptin constitutes a novel biomarker of degenerative aortic stenosis.
AB  - Copeptin is a new biomarker of cardiovascular diseases. Its diagnostic value in
      degenerative aortic valve stenosis (AS) with preserved left ventricle systolic
      function is unknown. We aimed to assess the association of serum copeptin levels
      with AS severity and coexistence of coronary artery disease (CAD). Sixty-four
      patients with AS and preserved left ventricle systolic function including 40 with
      severe degenerative AS (group sAS, effective orifice area EOA = 0.67 cm(2)) and
      24 with moderate degenerative AS (group mAS, EOA = 1.40 cm(2)) were enrolled into
      the study. Twenty-three patients without AS and heart failure, matched for age,
      sex, and CAD occurrence served as the control group (group C). Serum levels of
      copeptin and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured
      using enzyme-linked immunosorbent assay. The mean serum copeptin concentrations
      were significantly higher in patients with AS: sAS (405 pg/ml) and mAS (351
      pg/ml; sAS vs mAS P < 0.05), compared with group C (302 pg/ml, P < 0.05). Serum
      copeptin levels correlated inversely with EOA (r = -0.55; P < 0.001) in AS
      patients. There was no correlation between copeptin and NT-proBNP or association
      with the coexisting CAD. Receiver-operating characteristics analysis showed that
      copeptin was a good marker of severe/moderate AS (sensitivity 71 %; specificity
      87 %), with the optimized cut-off value of 354 pg/ml. Serum copeptin
      concentration constitutes a novel biomarker of degenerative AS. Coexisting CAD
      does not interfere with copeptin level. 

PMID- 23142955
TI  - Use of injectable spasticity management agents in a cancer center.
AB  - PURPOSE: This study aims to analyze the utilization and effectiveness of
      injectable spasticity medications by the physiatry team at a referral-based
      tertiary cancer center. METHODS: A retrospective review and analysis of patient
      and injection characteristics were obtained from patients who had received
      onabotulinum toxin or phenol nerve block injections from December 1, 2007 through
      January 31, 2012. Out of 3,724 physiatry consultations during this period, 20
      (less than 1 %) different cancer patients received a total of 54 total
      procedures. RESULTS: The majority of patients (17/20, 85 %) had a positive
      response to the injection. A positive response to the injection was defined by:
      (1) if the patient qualified to receive and was given another injection or (2) if
      there is a record of improvement if they did not receive another injection. A
      total of ten of 20 (50 %) patients received only one injection. Of these, seven
      of ten (70 %) reported a positive response to the injected agent. Those with only
      one injection tended to live farther away and die sooner. Four of 54 (7 %)
      injection procedures resulted in undesirable reported side effects (two for
      phenol, two for botulinum toxin). Nine of 54 (17 %) procedures occurred while the
      patients were on a chemotherapy protocol. All patients were injected at least 1
      year out from initial diagnosis.

PMID- 23142956
TI  - A new approach for rhenium(VII) recovery by using modified brown algae Laminaria
      japonica adsorbent.
AB  - Brown algae Laminaria japonica was chemically modified with sulfuric acid to
      obtain a crosslinked brown algae gel (CAS). The CAS gel showed a high affinity
      for Re(VII) comparing with other biomass gels, and the maximum adsorption
      capacity was evaluated as 37.20 mg g(-1) in case of pH 6, which could be
      explained by their different adsorption mechanisms. The adsorption equilibrium,
      kinetics and thermodynamic study for Re(VII) on the CAS gel was discussed in
      detail by the several models, such as Langmuir, Freundlich, Temkin and Dubinin
      Radushkevich model for kinetics analysis, the pseudo first, the second-order, the
      Elovich and intraparticle diffusion equation for equilibrium analysis.
      Reutilization of the CAS gel was confirmed up to three adsorption-elution cycles
      in column-mode operation with no damage of gel, packed in the column. The result
      also provides a new approach for the recovery of Re(VII) from Re-containing
      wastewater by using the modified brown algae gel.

PMID- 23142957
TI  - Human pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) after
      repeated doses taken 2 h apart.
AB  - BACKGROUND: 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is one of the most
      abused recreational drugs. Its usual pattern of misuse includes repeated doses
      taken over a short time period that could influence MDMA pharmacology and
      toxicity. OBJECTIVE: This study aims to evaluate the pharmacokinetics and
      pharmacologically induced effects of two MDMA consecutive doses separated by 2 h.
      METHODS: A randomized, double-blind, crossover, and placebo-controlled trial
      included ten male volunteers participating in two experimental sessions. MDMA was
      administered as a single 100-mg dose or as a repeated dose (50 mg followed by 100
      mg, administered at 2 h apart). Outcome variables included pharmacokinetics,
      physiological, subjective, and psychomotor effects. RESULTS: Following the
      repeated doses, plasma concentrations of MDMA were higher than those expected by
      simple dose accumulation (+16.2 % AUC; +12.8 % C (max)), but those of HMMA and
      HMA were significantly lower (-29.8 % AUC; -38.2 % C (max)). After the second
      dose, physiological effects, psychomotor performance, and subjective effects were
      lower than expected especially for euphoria and stimulation. MDMA-induced
      increases in diastolic and systolic arterial pressure and body temperature were
      in the range of those expected following MDMA concentrations. CONCLUSIONS: MDMA
      pharmacokinetics and metabolic disposition following two doses separated by 2 h
      show that the contribution of the first dose to the MDMA-induced mechanism-based
      metabolic inhibition was already apparent. The concentrations of MDMA after the
      second dose were slightly higher than expected. The effects on blood pressure and
      temperature after the second administration were slightly higher than those
      following the first, but for heart rate and subjective variables these were lower
      than expected considering the MDMA concentrations achieved, suggesting a possible
      tolerance phenomenon.

PMID- 23142958
TI  - Sensory reinforcement as a predictor of cocaine and water self-administration in
      rats.
AB  - RATIONALE: The ability of locomotor activity in a novel environment (Loco) and
      visual stimulus reinforcement (VSR) to predict acquisition of responding for
      cocaine and water reinforcers in the absence of explicit audiovisual signals was
      evaluated. METHODS: In Experiment 1 (Exp 1), rats (n = 60) were tested for VSR,
      followed by Loco, and finally acquisition of responding for cocaine (0.3
      mg/kg/inf). In Experiment 2 (Exp 2), rats (n = 32) were tested for VSR, followed
      by Loco, and finally acquisition of responding for water (0.01 mL/reinforcer).
      RESULTS: There were three main findings. First, Loco and VSR were significantly
      associated (Exp 1: r = 0.49, p < 0.00; Exp 2: r = 0.35, p < 0.05). Second,
      neither Loco (r = .00, p = 0.998) nor VSR (r = -0.12, p = 0.352) predicted
      acquisition of cocaine SA. Third, in the subgroup of animals that acquired
      cocaine SA, VSR (r = 0.41, p < 0.01) but not Loco (r = 0.28, p = 0.10) was
      positively associated with operant responding for cocaine. Both Loco and VSR
      (Loco: r = 0.37, p < 0.04; VSR: r = 0.51, p < 0.00) were positively associated
      with operant responding for water reinforcers. CONCLUSIONS: The results indicate
      that VSR is at least as good a predictor of cocaine reinforced responding as
      Loco. VSR was predictive of operant responding for both drug and water
      reinforcers, while Loco was found to be predictive of responding only for water
      reinforcers. In studies that present visual stimuli in association with drug
      delivery, Loco may be predicting acquisition of responding for VSR rather than
      drug.

PMID- 23142960
TI  - Current concept of neuromyelitis optica (NMO) and NMO spectrum disorders.
AB  - Neuromyelitis optica (NMO) has been described as a disease clinically
      characterised by severe optic neuritis (ON) and transverse myelitis (TM). Other
      features of NMO include female preponderance, longitudinally extensive spinal
      cord lesions (>3 vertebral segments), and absence of oligoclonal IgG bands . In
      spite of these differences from multiple sclerosis (MS), the relationship between
      NMO and MS has long been controversial. However, since the discovery of NMO-IgG
      or aquaporin-4 (AQP4) antibody (AQP4-antibody), an NMO-specific autoantibody to
      AQP4, the dominant water channel in the central nervous system densely expressed
      on end-feet of astrocytes, unique clinical features, MRI and other laboratory
      findings in NMO have been clarified further. AQP4-antibody is now the most
      important laboratory finding for the diagnosis of NMO. Apart from NMO, some
      patients with recurrent ON or recurrent longitudinally extensive myelitis alone
      are also often positive for AQP4-antibody. Moreover, studies of AQP4-antibody
      positive patients have revealed that brain lesions are not uncommon in NMO, and
      some patterns appear to be unique to NMO. Thus, the spectrum of NMO is wider than
      mere ON and TM. Pathological analyses of autopsied cases strongly suggest that
      unlike MS, astrocytic damage is the primary pathology in NMO, and experimental
      studies confirm the pathogenicity of AQP4-antibody. Importantly, therapeutic
      outcomes of some immunological treatments are different between NMO and MS,
      making early differential diagnosis of these two disorders crucial. We provide an
      overview of the epidemiology, clinical and neuroimaging features, immunopathology
      and therapy of NMO and NMO spectrum disorders. 

PMID- 23142959
TI  - Low dose naloxone attenuates the pruritic but not anorectic response to
      rimonabant in male rats.
AB  - RATIONALE: Previous research suggests that the acute anorectic effect of
      cannabinoid CB1 receptor antagonist/inverse agonists may be secondary to response
      competition from the compulsive scratching and grooming syndrome characteristic
      of these agents. OBJECTIVES: As the pruritic effect of rimonabant can be
      attenuated by the opioid receptor antagonist naloxone, these studies test the
      prediction that naloxone co-treatment should prevent acute rimonabant anorexia.
      METHODS: Two experiments comprehensively profiled the behavioural effects of an
      anorectic dose of rimonabant (1.5 mg/kg) in the absence or presence of naloxone
      (experiment 1: 0.01 or 0.1 mg/kg; experiment 2: 0.05 mg/kg). RESULTS: In both
      experiments, rimonabant not only significantly suppressed food intake and time
      spent eating but also induced compulsive scratching and grooming. In experiment
      1, although the lower dose of naloxone seemed to weakly attenuate the effects of
      rimonabant both on ingestive and compulsive behaviours, the higher dose more
      strongly suppressed the compulsive elements but did not significantly affect the
      anorectic response. The results of experiment 2 showed that naloxone at a dose
      which markedly attenuated rimonabant-induced grooming and scratching did not
      alter the effects of the compound on food intake or time spent feeding. The
      apparent independence of the ingestive and compulsive effects of rimonabant was
      confirmed by the observation that despite a 'normalising' effect of naloxone co
      treatment on behavioural structure (BSS), the opioid antagonist did not impact
      the suppressant effect of rimonabant on peak feeding. CONCLUSION: The acute
      anorectic response to rimonabant would not appear to be secondary to compulsive
      scratching and grooming.

PMID- 23142961
TI  - Tremor in primary adult-onset dystonia: prevalence and associated clinical
      features.
AB  - OBJECTIVE: To investigate the frequency and the main clinical features of tremor
      in primary adult-onset dystonia (PAOD). METHODS: This cross-sectional study was
      conducted on 429 patients with PAOD from eight Italian movement disorder centres.
      RESULTS: Of the 429 dystonic patients, 72 (16.7%) had tremor. Although sex and
      age at dystonia onset were similar in dystonic patients who had tremor and those
      who did not, patients who had tremor were affected more often by focal cervical
      dystonia and less often by focal blepharospasm. Dystonia had a greater tendency
      to spread in patients with tremor. According to the Movement Disorder Society
      Consensus Statement, tremor was classified as dystonic tremor (DT) in 43 patients
      and tremor associated with dystonia (TAWD) in 23 patients. Six patients had both
      types of tremor. Taking into account potential confounding by age at onset and
      body distribution of the corresponding dystonia type, all the clinical features
      in patients with DT and in those with TAWD were comparable except the tendency of
      dystonia to spread, which was greater in patients with DT. CONCLUSIONS: Tremor is
      a relatively common feature occurring in about 17% of patients with primary late
      onset dystonia. The association between tremor and dystonia spread suggests that
      this form of tremor may be a dystonic manifestation. Similarities in phenotypic
      features of DT and TAWD predominated over differences, suggesting that the two
      forms of tremor may be manifestations of the same disease. Differences in gender
      and body distribution of tremor between patients with dystonia and tremor and
      those of patients with essential tremor also suggest that tremor in dystonia and
      essential tremor are different entities.

PMID- 23142962
TI  - Cognitive impairment in the preclinical stage of dementia in FTD-3 CHMP2B
      mutation carriers: a longitudinal prospective study.
AB  - OBJECTIVE AND METHODS: A longitudinal study spanning over 8 years and including
      17 asymptomatic individuals with CHMP2B mutations was conducted to assess the
      earliest neuropsychological changes in autosomal dominant neurodegenerative
      disease frontotemporal dementia (FTD) linked to chromosome 3 (FTD-3). Subjects
      were assessed with neuropsychological tests in 2002, 2005 and 2010. RESULTS:
      Cross-sectional analyses showed that the mutation carriers scored lower on tests
      of psychomotor speed, working memory, executive functions and verbal memory than
      a control group consisting of not-at-risk family members and spouses.
      Longitudinal analyses showed a gradual decline in psychomotor speed, working
      memory capacity and global executive measures in the group of non-demented
      mutation carriers that was not found in the control group. In contrast, there
      were no significant group differences in domain scores on memory or visuospatial
      functions. On an individual level the cognitive changes over time varied
      considerably. CONCLUSION: Subjects with CHMP2B mutation show cognitive changes
      dominated by executive dysfunctions, years before they fulfil diagnostic criteria
      of FTD. However, there is great heterogeneity in the individual cognitive
      trajectories.

PMID- 23142963
TI  - iBAG: integrative Bayesian analysis of high-dimensional multiplatform genomics
      data.
AB  - MOTIVATION: Analyzing data from multi-platform genomics experiments combined with
      patients' clinical outcomes helps us understand the complex biological processes
      that characterize a disease, as well as how these processes relate to the
      development of the disease. Current data integration approaches are limited in
      that they do not consider the fundamental biological relationships that exist
      among the data obtained from different platforms. Statistical Model: We propose
      an integrative Bayesian analysis of genomics data (iBAG) framework for
      identifying important genes/biomarkers that are associated with clinical outcome.
      This framework uses hierarchical modeling to combine the data obtained from
      multiple platforms into one model. RESULTS: We assess the performance of our
      methods using several synthetic and real examples. Simulations show our
      integrative methods to have higher power to detect disease-related genes than non
      integrative methods. Using the Cancer Genome Atlas glioblastoma dataset, we apply
      the iBAG model to integrate gene expression and methylation data to study their
      associations with patient survival. Our proposed method discovers multiple
      methylation-regulated genes that are related to patient survival, most of which
      have important biological functions in other diseases but have not been
      previously studied in glioblastoma. AVAILABILITY:
      http://odin.mdacc.tmc.edu/~vbaladan/. CONTACT: veera@mdanderson.org SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 23142964
TI  - Density parameter estimation for finding clusters of homologous proteins--tracing
      actinobacterial pathogenicity lifestyles.
AB  - MOTIVATION: Homology detection is a long-standing challenge in computational
      biology. To tackle this problem, typically all-versus-all BLAST results are
      coupled with data partitioning approaches resulting in clusters of putative
      homologous proteins. One of the main problems, however, has been widely
      neglected: all clustering tools need a density parameter that adjusts the number
      and size of the clusters. This parameter is crucial but hard to estimate without
      gold standard data at hand. Developing a gold standard, however, is a difficult
      and time consuming task. Having a reliable method for detecting clusters of
      homologous proteins between a huge set of species would open opportunities for
      better understanding the genetic repertoire of bacteria with different
      lifestyles. RESULTS: Our main contribution is a method for identifying a suitable
      and robust density parameter for protein homology detection without a given gold
      standard. Therefore, we study the core genome of 89 actinobacteria. This allows
      us to incorporate background knowledge, i.e. the assumption that a set of
      evolutionarily closely related species should share a comparably high number of
      evolutionarily conserved proteins (emerging from phylum-specific housekeeping
      genes). We apply our strategy to find genes/proteins that are specific for
      certain actinobacterial lifestyles, i.e. different types of pathogenicity. The
      whole study was performed with transitivity clustering, as it only requires a
      single intuitive density parameter and has been shown to be well applicable for
      the task of protein sequence clustering. Note, however, that the presented
      strategy generally does not depend on our clustering method but can easily be
      adapted to other clustering approaches. AVAILABILITY: All results are publicly
      available at http://transclust.mmci.uni-saarland.de/actino_core/ or as
      Supplementary Material of this article. CONTACT: roettger@mpi-inf.mpg.de
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 23142965
TI  - DLocalMotif: a discriminative approach for discovering local motifs in protein
      sequences.
AB  - MOTIVATION: Local motifs are patterns of DNA or protein sequences that occur
      within a sequence interval relative to a biologically defined anchor or landmark.
      Current protein motif discovery methods do not adequately consider such
      constraints to identify biologically significant motifs that are only weakly over
      represented but spatially confined. Using negatives, i.e. sequences known to not
      contain a local motif, can further increase the specificity of their discovery.
      RESULTS: This article introduces the method DLocalMotif that makes use of
      positional information and negative data for local motif discovery in protein
      sequences. DLocalMotif combines three scoring functions, measuring degrees of
      motif over-representation, entropy and spatial confinement, specifically designed
      to discriminatively exploit the availability of negative data. The method is
      shown to outperform current methods that use only a subset of these motif
      characteristics. We apply the method to several biological datasets. The analysis
      of peroxisomal targeting signals uncovers several novel motifs that occur
      immediately upstream of the dominant peroxisomal targeting signal-1 signal. The
      analysis of proline-tyrosine nuclear localization signals uncovers multiple novel
      motifs that overlap with C2H2 zinc finger domains. We also evaluate the method on
      classical nuclear localization signals and endoplasmic reticulum retention
      signals and find that DLocalMotif successfully recovers biologically relevant
      sequence properties. AVAILABILITY: http://bioinf.scmb.uq.edu.au/dlocalmotif/

PMID- 23142966
TI  - CIS-ZnS quantum dots for self-aligned liquid crystal molecules with superior
      electro-optic properties.
AB  - We demonstrate self-aligned and high-performance liquid crystal (LC) systems
      doped with 1-dimensional (1D) chain-like clusters of CuInS(2) (CIS)-ZnS core
      shell quantum dots (QDs). By changing the cell fabrication method of the LC-QD
      composites, we can selectively control the orientation of the LC molecules
      between the homogeneous and homeotropic states without conventional LC alignment
      layers. The homeotropic alignment of LCs was achieved by random dropcasting and
      the homogeneous alignment was performed using a capillary injection of LC-QDs due
      to the random or linear diffusion of QD clusters into ITO defects. The
      electrically compensated bend (ECB)- and vertically aligned (VA) mode LC displays
      (LCDs) containing our LC-QD composite both showed superior electro-optic (EO)
      properties. A 37.1% reduction in the threshold voltage (V(th)) and a 36.6%
      decrease in the response time were observed for ECB mode LCDs, and a 47.0%
      reduction in the V(th) and a 38.3% decrease in the response time were observed
      for VA mode LCDs, meaning that the proposed LC-QD composites have a great
      potential for the production of advanced flexible LCDs.

PMID- 23142967
TI  - A comparative study of bovine and porcine pericardium to highlight their
      potential advantages to manufacture percutaneous cardiovascular implants.
AB  - RATIONALE: Prosthetic heart valves designed to be implanted percutaneously must
      be loaded within delivery catheters whose diameter can be as low as 18 F (6 mm).
      This mandatory crimping of the devices may result in deleterious damages to the
      tissues used for valve manufacturing. As bovine and porcine pericardial tissue
      are currently given preference because of their excellent availability and
      traceability, a preliminary comparative study was undertaken to highlight their
      potential advantages. MATERIALS AND METHODS: Bovine and pericardium patches were
      compared morphologically (light microscopy, scanning electron microscopy and
      transmission electron microscopy). The acute thrombogenicity of both materials
      was measured in term of platelet uptake and observed by scanning electron
      microscopy, porcine intact and injured arteries being used as controls. The
      pericardium specimens were also subjected to uniaxial tensile tests to compare
      their respective mechanical characteristics. RESULTS: Both pericardiums showed a
      layered architecture of collagen bundles presenting some interstitial cells. They
      displayed wavy crimps typical of an unloaded collagenous tissue. The collagen
      bundles were not bound together and the fibrils were parallel with characteristic
      periodicity patterns of cross striations. The mesothelial cells found in vivo on
      the serous surface were no longer present due to tissue processing, but the
      adjacent structure was far more compacted when compared to the fibrous side. The
      fibrinocollagenous surfaces were found to be more thrombogenic for both bovine
      and porcine tissues and the serous side of the porcine pericardium retained more
      platelets when compared to the bovine samples, making the acute thrombogenicity
      more important in the porcine pericardium. CONCLUSION: Both bovine and porcine
      pericardium used in cardiovascular implantology can be selected to manufacture
      percutaneous heart valves. The selection of one pericardium preferably to the
      other should deserve additional testing regarding the innocuousness of crimping
      when loaded in delivery catheters and the long-term durability after percutaneous
      deployment.

PMID- 23142968
TI  - Whole-genome-wide association study in the Bulgarian population reveals HHAT as
      schizophrenia susceptibility gene.
AB  - OBJECTIVE: Schizophrenia, the most common major psychiatric disorder (or group of
      disorders), entails severe decline of higher functions, principally with
      alterations in cognitive functioning and reality perception. Both genetic and
      environmental factors are involved in its pathogenesis; however, its genetic
      background still needs to be clarified. The objective of the study was to reveal
      genetic markers associated with schizophrenia in the Bulgarian population.
      METHODS: We have conducted a genome-wide association study using 554 496 single
      nucleotide polymorphisms (SNPs) in 188 affected and 376 unaffected Bulgarian
      individuals. Subsequently, the 100 candidate SNPs that revealed the smallest P
      values were further evaluated in an additional set of 99 case and 328 control
      samples. RESULTS: We found a significant association between schizophrenia and
      the intronic SNP rs7527939 in the HHAT gene (P-value of 6.49*10 with an odds
      ratio of 2.63, 95% confidence interval of 1.89-3.66). We also genotyped
      additional SNPs within a 58-kb linkage disequilibrium block surrounding the
      landmark SNP. CONCLUSION: We suggest rs7527939 to be the strongest indicator of
      susceptibility to schizophrenia in the Bulgarian population within the HHAT
      locus.

PMID- 23142969
TI  - Noninvasive diagnostic method for idiopathic portal hypertension based on
      measurements of liver and spleen stiffness by ARFI elastography.
AB  - BACKGROUND: Acoustic radiation force impulse (ARFI) elastography is an ultrasound
      technique that is capable of measuring tissue stiffness noninvasively. It is
      difficult to differentiate idiopathic portal hypertension (IPH) from liver
      cirrhosis (LC) or chronic hepatitis (CH), and liver biopsy is essential. We
      investigated whether it would be possible to noninvasively diagnose IPH by
      measuring the stiffness of the liver and spleen by ARFI. METHODS: The subjects
      were 17 IPH patients, 25 LC patients, 20 CH patients, and 20 normal controls
      (NC). We measured liver stiffness, spleen stiffness, and the spleen/liver
      stiffness ratio, and plotted ROC curves. RESULTS: The median value of liver
      stiffness in the IPH group was lower than that in the LC group (p = 0.00077) and
      about the same as in the CH group (p = 0.79). The median value of spleen
      stiffness was highest in the IPH group (IPH vs. LC group, p = 0.003; IPH vs. CH
      group, p < 0.00001). The spleen/liver stiffness ratio was lower in the LC group
      and in the CH group, and higher in the IPH group (p < 0.001, respectively). When
      an ROC curve of spleen/liver stiffness ratios was plotted to differentiate
      between the IPH group and the combined group of patients with other liver
      diseases (LC + CH group), when a cutoff value of 1.71 was used, the AUROC was
      0.933 sensitivity 0.941, specificity 0.800, and accuracy 0.839. CONCLUSION:
      Measuring the spleen/liver stiffness ratio by ARFI made it possible to
      noninvasively, specifically, and accurately diagnose IPH.

PMID- 23142970
TI  - Comparison of long-term outcomes after endoscopic sphincterotomy versus
      endoscopic papillary balloon dilation: a propensity score-based cohort analysis.
AB  - BACKGROUND: Endoscopic sphincterotomy (ES) is widely performed in patients with
      common bile duct stones (CBDS). However, the long-term outcomes of patients
      following ES have not been sufficiently elucidated. Impaired papillary function
      following ES may result in additional late complications. In contrast, endoscopic
      papillary balloon dilation (EPBD)-another option for treating CBDS-is expected to
      preserve papillary function. This study aimed to compare the long-term outcomes
      of patients with CBDS treated with ES to those treated with EPBD in a large
      cohort. In addition, a subgroup analysis was performed, according to gallbladder
      (GB) status. METHODS: A cohort study was performed using propensity score
      matching to reduce treatment selection bias. This involved the analysis of follow
      up data for 1086 patients who underwent EPBD or ES for CBDS. RESULTS: Propensity
      score matching extracted 246 pairs of patients. The median (interquartile range)
      follow-up period after EPBD or ES was 93.5 (46.8-129.2) months and 90 (42-139.3)
      months, respectively. The incidence of CBDS recurrence after EPBD and ES were 8.5
      and 15.0 %, respectively. The hazard ratio (95 % CI) was 0.577 (0.338-0.986) (P =
      0.044). Based on the status of the GB, the incidence of CBDS recurrence was
      significantly different between post-EPBD and post-ES in the group with
      cholecystectomy after EPBD/ES (P = 0.013). CONCLUSIONS: The incidence of biliary
      complications was significantly lower in patients after EPBD than in those after
      ES, and this outcome appeared most markedly in patients who also underwent
      cholecystectomy.

PMID- 23142971
TI  - Wilms' tumor 1 gene modulates Fas-related death signals and anti-apoptotic
      functions in hepatocellular carcinoma.
AB  - BACKGROUND: The Wilms' tumor 1 (WT1) gene is known to be overexpressed in
      hepatocellular carcinoma (HCC) and to upregulate tumor growth and oncogenic
      potential, although the detailed mechanisms remain to be elucidated. METHODS: We
      identified host genes involved in WT1 gene modulation of human liver cancer cell
      lines in vitro, and further characterized genes related to apoptosis. Moreover,
      we evaluated the alteration of genes by WT1 in 40 HCC and 58 non-HCC human liver
      samples collected at resection. RESULTS: Analysis of the effect of small
      interfering RNAs-mediated knock-down of WT1 on apoptosis using an annexin V
      labeling assay, and on modulation of the activity of caspases-3, -8 and -9,
      indicated that WT1 has an anti-apoptotic role. We identified three apoptosis
      related genes that were modulated by WT1; the cellular FLICE-inhibitory proteins
      (cFLIP) gene was upregulated, and Fas-associated death domain (FADD) and nuclear
      factor kappa B (NF-kappaB) were downregulated. Interestingly, knock-down of FADD
      or NF-kappaB resulted in the upregulation of WT1, and the expression of cFLIP
      changed in parallel with WT1 expression. We further evaluated WT1-mediated
      alteration of genes in HCC and non-HCC human liver samples. Both HCC and non-HCC
      tissues that expressed relatively high levels of WT1 showed cFLIP overexpression.
      CONCLUSIONS: WT1 modulates cFLIP, FADD and NF-kappaB, and has an anti-apoptotic
      role in HCC. This mechanism of action of WT1 could be related to the tumor growth
      and oncogenic potential of HCC.

PMID- 23142972
TI  - Heart rate reduction with ivabradine prevents thyroid hormone-induced cardiac
      remodeling in rat.
AB  - Ivabradine slows the heart rate (HR) by selectively inhibiting the I(f) current
      in the sinus node without a negative inotropic effect. We aimed to investigate
      the effects of ivabradine on thyroid hormone-induced left ventricular (LV)
      remodeling and ion channel activity in rats. Thirty Sprague-Dawley rats were
      randomly selected into the groups of control, injection of L-thyroxine (T4, 100
      MUg/kg/day), and injection of L-thyroxine with ivabradine (T4-Iva, T4 + 10
      mg/kg/day). Circumferential (S circ), radial (S rad), and longitudinal (S long)
      strains were assessed by speckle tracking echocardiography (STE). Myocardial
      width and fibrosis were assessed from histological LV cross sections, and
      electrophysiological analysis was done by patch clamp method. In comparison with
      the control group, the T4 group showed significantly increased HR and LV end
      systolic diameter (LVESD), reduced S circ (-16.04 +/- 3.95 vs. -7.84 +/- 2.98 %,
      p < 0.001), S rad (20.94 +/- 3.81 vs. 40.57 +/- 6.70 %, p < 0.001), and S long (
      15.26 +/- 5.15 vs. -23.83 +/- 5.19 %, p < 0.001), despite the 59.5 % increase of
      average I Ca,L density at 0 mV (13.4 +/- 1.2 pA/pF) compared to control group
      (8.4 +/- 0.8 pA/pF). Treatment with ivabradine significantly reduced HR and
      LVESD, improved SRcirc, S long and SRlong in the T4 group, and the average I Ca,L
      density at 0 mV in T4-Iva groups (9.9 +/- 1.6 pA/pF) was restored to the control
      level. Morphologically, the T4 group showed significantly increased cardiomyocyte
      width (25.3 +/- 1.89 vs. 18.90 +/- 1.14 MUm in control, p < 0.001) and fibrosis,
      which were not significantly changed by ivabradine. In conclusion, selective HR
      reduction by ivabradine attenuates thyroid hormone-induced reduction of
      myocardial deformation and altered intracellular Ca(2+) handling without
      modification of the myocyte hypertrophy with fibrosis in rats.

PMID- 23142973
TI  - Cellular and computational studies of proteasome inhibition and apoptosis
      induction in human cancer cells by amino acid Schiff base-copper complexes.
AB  - Proliferation and apoptosis pathways are tightly regulated in a cell by the
      ubiquitin-proteasome system (UPS) and alterations in the UPS may result in
      cellular transformation or other pathological conditions. Indeed, the proteasome
      is often found to be overactive in cancer cells. It has also been found that
      cancer cells are more sensitive to proteasome inhibition than normal cells, and
      therefore proteasome inhibitors are pursued as antitumor drugs. The use of the
      proteasome inhibitor Bortezomib for treatment of multiple myeloma and mantle cell
      lymphoma has proved this principle. Recent studies have suggested that copper
      complexes can inhibit proteasome activity and induce apoptosis in some human
      cancer cells. However, the involved molecular mechanism is unknown. In this
      study, we investigated the biological activities of four amino acid Schiff base
      copper(II) complexes by using human breast (MDA-MB-231 and MCF-7) and prostate
      (PC-3) cancer cells. The complexes C1 and C3, but not their counterparts C2 and
      C4, inhibit the chymotrypsin-like activity of purified 20S proteasome and human
      cancer cellular 26S proteasome, cause accumulation of proteasome target proteins
      Bax and IkappaB-alpha, and induce growth inhibition and apoptosis in
      concentration- and time-dependent manners. Docking analysis shows that C1, but
      not C2 has hydrophobic, pi-pi, pi-cation and hydrogen bond interactions with the
      proteasomal chymotrypsin-like pocket and could stably fit into the S3 region,
      leading to specific inhibition. Our study has identified the mechanism of action
      of these copper complexes on inhibiting tumor cell proteasome and suggested their
      great potential as novel anticancer agents.

PMID- 23142974
TI  - The molecular mechanisms of antimetastatic ruthenium compounds explored through
      DIGE proteomics.
AB  - DIGE (difference in gel electrophoresis) proteomics is exploited here to gain
      insight into the molecular mechanisms of two established ruthenium-based
      antimetastatic agents, namely trans-[tetrachloro (DMSO)
      (imidazole)ruthenate(III)] (NAMI-A) and [Ru(eta(6)-toluene)Cl(2)(PTA)] (RAPTA-T),
      where PTA is 1,3,5-triaza-7-phosphaadamantane. Following 24h exposure of A2780/S
      human ovarian carcinoma cells to pharmacologically relevant concentrations of
      either ruthenium compound, 2D-DIGE proteomic analysis evidenced only few
      differentially expressed proteins with respect to controls. Successive mass
      spectrometry measurements, MALDI-TOF (matrix assisted laser desorption ionization
      time of flight) or LC-ESI/MS-MS (liquid chromatography-electrospray
      ionization/multi-stage mass spectrometry), allowed identification of most altered
      protein spots, some of which were associated to perturbations in specific
      cellular functions. Direct insight into the cellular effects of the investigated
      metallodrugs is thus achieved. Notably, the patterns of protein alterations
      induced by NAMI-A and RAPTA-T are quite similar to each other while being deeply
      different from those of cisplatin. To the best of our knowledge this is the first
      proteomic study on human cancer cells investigating responses to antimetastatic
      ruthenium drugs. The key role of new "omic" approaches for deciphering the
      elusive and complex biochemical mechanisms through which anticancer metallodrugs
      produce their pharmacological effects is further documented.

PMID- 23142975
TI  - Splice variants of the Alzheimer's disease beta-secretase, BACE1.
AB  - Cleavage of the amyloid precursor protein by enzymes commonly referred to as beta
      and gamma-secretase constitute an important process in the pathogenesis of
      Alzheimer's disease (AD). The regulation of this process is therefore an
      important subject of investigation. Numerous sources of endogenous regulation
      have been identified, and one of these is the relative abundance and regulation
      of splice variants of the beta-secretase, BACE1 (beta-site amyloid precursor
      protein cleaving enzyme 1). In this review, we will briefly discuss the main
      characteristics of BACE1, review the different variants of this enzyme that have
      been identified to date, and highlight their possible implication in AD.

PMID- 23142976
TI  - Noncanonical E2 recruitment by the autophagy E1 revealed by Atg7-Atg3 and Atg7
      Atg10 structures.
AB  - Core functions of autophagy are mediated by ubiquitin-like protein (UBL)
      cascades, in which a homodimeric E1 enzyme, Atg7, directs the UBLs Atg8 and Atg12
      to their respective E2 enzymes, Atg3 and Atg10. Crystallographic and mutational
      analyses of yeast (Atg7-Atg3)(2) and (Atg7-Atg10)(2) complexes reveal
      noncanonical, multisite E1-E2 recognition in autophagy. Atg7's unique N-terminal
      domain recruits distinctive elements from the Atg3 and Atg10 'backsides'. This,
      along with E1 and E2 conformational variability, allows presentation of
      'frontside' Atg3 and Atg10 active sites to the catalytic cysteine in the C
      terminal domain from the opposite Atg7 protomer in the homodimer. Despite
      different modes of binding, the data suggest that common principles underlie
      conjugation in both noncanonical and canonical UBL cascades, whereby flexibly
      tethered E1 domains recruit E2s through surfaces remote from their active sites
      to juxtapose the E1 and E2 catalytic cysteines.

PMID- 23142977
TI  - Structure of the vacuolar-type ATPase from Saccharomyces cerevisiae at 11-A
      resolution.
AB  - Vacuolar-type ATPases (V-type ATPases) in eukaryotic cells are large membrane
      protein complexes that acidify various intracellular compartments. The enzymes
      are regulated by dissociation of the V(1) and V(O) regions of the complex. Here
      we present the structure of the Saccharomyces cerevisiae V-type ATPase at 11-A
      resolution by cryo-EM of protein particles in ice. The structure explains many
      cross-linking and protein interaction studies. Docking of crystal structures
      suggests that inhibition of ATPase activity by the dissociated V(1) region
      involves rearrangement of the N- and C-terminal domains of subunit H and also
      suggests how this inhibition is triggered upon dissociation. We provide support
      for this model by demonstrating that mutation of subunit H to increase the
      rigidity of the linker between its two domains decreases its ability to inhibit
      ATPase activity.

PMID- 23142978
TI  - Structure of the pre-60S ribosomal subunit with nuclear export factor Arx1 bound
      at the exit tunnel.
AB  - Preribosomal particles evolve in the nucleus through transient interaction with
      biogenesis factors before export to the cytoplasm. Here, we report the
      architecture of the late pre-60S particle, purified from Saccharomyces
      cerevisiae, through Arx1, a nuclear export factor with structural homology to
      methionine aminopeptidases, or its binding partner Alb1. Cryo-EM reconstruction
      of the Arx1 particle at 11.9-A resolution reveals regions of extra density on the
      pre-60S particle attributed to associated biogenesis factors, confirming the
      immature state of the nascent subunit. One of these densities could be
      unambiguously assigned to Arx1. Immunoelectron microscopy and UV cross-linking
      localize Arx1 close to the ribosomal exit tunnel, in direct contact with ES27, a
      highly dynamic eukaryotic rRNA expansion segment. The binding of Arx1 at the exit
      tunnel may position this export factor to prevent premature recruitment of
      ribosome-associated factors active during translation.

PMID- 23142979
TI  - Structure of the variant histone H3.3-H4 heterodimer in complex with its
      chaperone DAXX.
AB  - Mammalian histone H3.3 is a variant of the canonical H3.1 essential for genome
      reprogramming in fertilized eggs and maintenance of chromatin structure in
      neuronal cells. An H3.3-specific histone chaperone, DAXX, directs the deposition
      of H3.3 onto pericentric and telomeric heterochromatin. H3.3 differs from H3.1 by
      only five amino acids, yet DAXX can distinguish the two with high precision. By a
      combination of structural, biochemical and cell-based targeting analyses, we show
      that Ala87 and Gly90 are the principal determinants of human H3.3 specificity.
      DAXX uses a shallow hydrophobic pocket to accommodate the small hydrophobic Ala87
      of H3.3, whereas a polar binding environment in DAXX prefers Gly90 in H3.3 over
      the hydrophobic Met90 in H3.1. An H3.3-H4 heterodimer is bound by the histone
      binding domain of DAXX, which makes extensive contacts with both H3.3 and H4.

PMID- 23142980
TI  - Molecular basis for H3K36me3 recognition by the Tudor domain of PHF1.
AB  - The PHD finger protein 1 (PHF1) is essential in epigenetic regulation and genome
      maintenance. Here we show that the Tudor domain of human PHF1 binds to histone H3
      trimethylated at Lys36 (H3K36me3). We report a 1.9-A resolution crystal structure
      of the Tudor domain in complex with H3K36me3 and describe the molecular mechanism
      of H3K36me3 recognition using NMR. Binding of PHF1 to H3K36me3 inhibits the
      ability of the Polycomb PRC2 complex to methylate Lys27 of histone H3 in vitro
      and in vivo. Laser microirradiation data show that PHF1 is transiently recruited
      to DNA double-strand breaks, and PHF1 mutants impaired in the H3K36me3
      interaction exhibit reduced retention at double-strand break sites. Together, our
      findings suggest that PHF1 can mediate deposition of the repressive H3K27me3 mark
      and acts as a cofactor in early DNA-damage response.

PMID- 23142981
TI  - Ancient, giant riboswitches at atomic resolution.

PMID- 23142982
TI  - Noncanonical G recognition mediates KSRP regulation of let-7 biogenesis.
AB  - Let-7 is an important tumor-suppressive microRNA (miRNA) that acts as an on-off
      switch for cellular differentiation and regulates the expression of a set of
      human oncogenes. Binding of the human KSRP protein to let-7 miRNA precursors
      positively regulates their processing to mature let-7, thereby contributing to
      control of cell proliferation, apoptosis and differentiation. Here we analyze the
      molecular basis for KSRP-let-7 precursor selectivity and show how the third KH
      domain of the protein recognizes a G-rich sequence in the pre-let-7 terminal loop
      and dominates the interaction. The structure of the KH3-RNA complex explains the
      protein recognition of this noncanonical KH target sequence, and we demonstrate
      that the specificity of this binding is crucial for the functional interaction
      between the protein and the miRNA precursor.

PMID- 23142983
TI  - Noncanonical recognition and UBL loading of distinct E2s by autophagy-essential
      Atg7.
AB  - Autophagy requires ubiquitin-like Atg8 and Atg12 conjugation systems, where Atg7
      has a critical role as the sole E1 enzyme. Although Atg7 recognizes two distinct
      E2s, Atg3 and Atg10, it is not understood how Atg7 correctly loads these E2s with
      their cognate ubiquitin-like proteins, Atg8 and Atg12. Here, we report the
      crystal structures of the N-terminal domain of Atg7 bound to Atg10 or Atg3 of
      thermotolerant yeast and plant homologs. The observed Atg7-Atg10 and Atg7-Atg3
      interactions, which resemble each other but are quite distinct from the canonical
      E1-E2 interaction, makes Atg7 suitable for transferring Atg12 to Atg10 and Atg8
      to Atg3 by a trans mechanism. Notably, in vitro experiments showed that Atg7
      loads Atg3 and Atg10 with Atg8 and Atg12 in a nonspecific manner, which suggests
      that cognate conjugate formation in vivo is not an intrinsic quality of Atg7.

PMID- 23142984
TI  - Dynamic switch of the signal recognition particle from scanning to targeting.
AB  - Ribosomes synthesizing inner membrane proteins in Escherichia coli are targeted
      to the membrane by the signal recognition particle (SRP) pathway. By rapid
      kinetic analysis we show that after initial binding to the ribosome, SRP
      undergoes dynamic fluctuations in search of additional interactions. Non
      translating ribosomes, or ribosomes synthesizing non-membrane proteins, do not
      provide these contacts, allowing SRPs to dissociate rapidly. A nascent peptide in
      the exit tunnel stabilizes SRPs in a standby state. Binding to the emerging
      signal-anchor sequence (SAS) of a nascent membrane protein halts the fluctuations
      of SRP, resulting in complex stabilization and recruitment of the SRP receptor.
      We propose a kinetic model where SRP rapidly scans all ribosomes until it
      encounters a ribosome exposing an SAS. Binding to the SAS switches SRP into the
      targeting mode, in which dissociation is slow and docking of the SRP receptor is
      accelerated.

PMID- 23142985
TI  - Cryo-EM structures of Arx1 and maturation factors Rei1 and Jjj1 bound to the 60S
      ribosomal subunit.
AB  - Eukaryotic ribosome biogenesis requires many protein factors that facilitate the
      assembly, nuclear export and final maturation of 40S and 60S particles. We have
      biochemically characterized ribosomal complexes of the yeast 60S-biogenesis
      factor Arx1 and late-maturation factors Rei1 and Jjj1 and determined their cryo
      EM structures. Arx1 was visualized bound to the 60S subunit together with Rei1,
      at 8.1-A resolution, to reveal the molecular details of Arx1 binding whereby Arx1
      arrests the eukaryotic-specific rRNA expansion segment 27 near the polypeptide
      tunnel exit. Rei1 and Jjj1, which have been implicated in Arx1 recycling, bind in
      the vicinity of Arx1 and form a network of interactions. We suggest that, in
      addition to the role of Arx1 during pre-60S nuclear export, the binding of Arx1
      conformationally locks the pre-60S subunit and inhibits the premature association
      of nascent chain-processing factors to the polypeptide tunnel exit.

PMID- 23142986
TI  - X-ray structure of the Yersinia pestis heme transporter HmuUV.
AB  - HmuUV is a bacterial ATP-binding cassette (ABC) transporter that catalyzes heme
      uptake into the cytoplasm of the gram-negative pathogen Yersinia pestis. We
      report the crystal structure of HmuUV at 3.0 A resolution in a nucleotide-free
      state, which features a heme translocation pathway in an outward-facing
      conformation, poised to accept a heme from the cognate periplasmic binding
      protein HmuT. A new assay allowed us to determine in vitro rates of HmuUV
      catalyzed heme transport into proteoliposomes and to establish the role of
      conserved residues in the translocation pathway of HmuUV and at the interface
      with HmuT. Differences in architecture relative to the related vitamin B(12)
      transporter BtuCD suggest an adaptation of HmuUV for its smaller substrate. Our
      study also suggests that type II ABC importers, which include bacterial iron
      siderophore, heme and cobalamin transporters, have a coupling mechanism distinct
      from that of other ABC transporters.

PMID- 23142987
TI  - A direct interaction between DCP1 and XRN1 couples mRNA decapping to 5'
      exonucleolytic degradation.
AB  - The removal of the mRNA 5' cap structure by the decapping enzyme DCP2 leads to
      rapid 5'->3' mRNA degradation by XRN1, suggesting that the two processes are
      coordinated, but the coupling mechanism is unknown. DCP2 associates with the
      decapping activators EDC4 and DCP1. Here we show that XRN1 directly interacts
      with EDC4 and DCP1 in human and Drosophila melanogaster cells, respectively. In
      D. melanogaster cells, this interaction is mediated by the DCP1 EVH1 domain and a
      DCP1-binding motif (DBM) in the XRN1 C-terminal region. The NMR structure of the
      DCP1 EVH1 domain bound to the DBM reveals that the peptide docks at a conserved
      aromatic cleft, which is used by EVH1 domains to recognize proline-rich ligands.
      Our findings reveal a role for XRN1 in decapping and provide a molecular basis
      for the coupling of decapping to 5'->3' mRNA degradation.

PMID- 23142988
TI  - Pattern of postoperative recurrence and hepatic and/or pulmonary resection for
      liver and/or lung metastases from esophageal carcinoma.
AB  - BACKGROUND: We assessed the benefit of hepatic and pulmonary resections in
      patients with liver and lung recurrences, respectively, after resection of
      esophageal carcinoma. METHODS: The study population consisted of 138 consecutive
      patients with recurrent esophageal carcinoma after esophagectomy conducted
      between 2003 and 2005. The pattern, timing of appearance, and the prognosis of
      these recurrences were investigated, paying particular attention to those
      undergoing hepatic and pulmonary resections. RESULTS: In total, 55 and 92
      patients developed locoregional and distant-organ metastases 13 and 6 months
      (median) after surgery, respectively, including 9 patients with both types of
      recurrence. The distant-organ metastases were found in the liver (n = 26), lung
      (n = 27), bone (n = 21), and other organs (n = 29). Patients with pulmonary
      recurrences had a better overall prognosis (median survival after recurrence
      detection 13 months) than those with hepatic metastases (5 months) or nonhepatic
      nonpulmonary metastases. (3 months) Hepatic and pulmonary resections were carried
      out in patients with oligonodular (n = <= 2) isolated liver and lung metastases
      (n = 5, respectively). Although the survivals of patients with lung metastases
      who were treated/not treated by pulmonary resection were different (median
      survival: 48 vs. 10 months, p < 0.01), the difference in the survivals between
      patients with hepatic metastases who were treated/not treated by hepatic
      resection reached only borderline statistical significance (13 vs. 5 months, p =
      0.06). CONCLUSIONS: Resection of pulmonary metastases yields a survival benefit
      in properly selected patients. The benefit of resection for hepatic metastases
      remains controversial.

PMID- 23142989
TI  - Colectomy in intensive care patients: operative findings and outcomes.
AB  - BACKGROUND: With a critical illness, intestinal complications are associated with
      high morbidity and mortality. METHODS: Operative findings and outcomes of 77
      intensive care unit (ICU) patients treated with colectomy are described. RESULTS:
      Three conditions led to colectomy: sepsis (S group; n = 31), fulminant
      Clostridium difficile colitis (Cl group; n = 25), and cardiovascular surgery (CV
      group; n = 21). The median Acute Physiology and Chronic Health score was >25 in
      all groups. Thickening and distension of the colon was more frequent in the Cl
      group (p = 0.001), and ischemia was more frequent in the S and CV groups (p <
      0.001). Widespread necrosis was more frequent in the CV patients (p = 0.001). The
      kappa value for ischemic operative findings and histologic necrosis was 0.64 (95
      % confidence interval 0.49-0.79). Hospital mortality was 35 % without multiple
      organ failure (MOF) (n = 31) and 74 % with MOF (n = 46) (p < 0.001). Overall, 38
      % were alive at the 1-year follow-up. CONCLUSIONS: Although colectomy in ICU
      patients is associated with high hospital mortality, patients who survive beyond
      their hospital stay have a good 1-year outcome.

PMID- 23142990
TI  - Influence of scanning density on macular choroidal volume measurement using
      spectral-domain optical coherence tomography.
AB  - BACKGROUND: To evaluate the impact of scanning density on macular choroidal
      volume measurement using spectral-domain optical coherence tomography (SD-OCT).
      METHODS: Thirty eyes of normal subjects underwent consecutive raster choroidal
      scanning protocols using SD-OCT in enhanced-depth imaging mode. Manual choroidal
      segmentation was performed using the built-in automated retinal segmentation
      software to obtain five analyses with different inter-scan distances, including
      inter-scan distances of 30 MUm, 60 MUm, 120 MUm, 240 MUm, and 480 MUm. The built
      in software of the device automatically generated the choroidal thickness and
      volume map in the similar manner as for the retinal volume map, using the
      standardized Early Treatment Diabetic Retinopathy Study (ETDRS) grid. For each
      raster scan, mean absolute difference and relative difference of mean foveal
      choroidal thickness (FCT), foveal choroidal volume (FCV) and total macular
      choroidal volume (TCV) in comparison to "true value" (i.e., 30-MUm inter-scan
      distance) were calculated. RESULTS: The maximum relative differences were 10% and
      16% for TCV and FCV respectively. For mean FCT, the maximum absolute difference
      was 31 MUm, and maximum relative difference was 12.7%. No statistically
      significant differences were found in measurements of mean foveal choroidal
      thickness (p = 0.912) and volume (p = 0.944), as well as macular choroidal volume
      (p = 0.912), with varying inter-scan distance. CONCLUSIONS: Our study shows that
      approximately 16 scans over the macula with a inter-scan distance of 480 MUm is
      sufficient to provide a clinically relevant and reliable choroidal
      thickness/volume map. This information could be useful in the design of choroidal
      scanning protocols for future clinical trials.

PMID- 23142991
TI  - Gas tamponade for myopic foveoschisis with foveal detachment.
AB  - PURPOSE: To evaluate the effects of gas tamponade without vitrectomy in patients
      with myopic foveoschisis and foveal detachment. METHODS: We examined 10 eyes of
      10 patients with myopic foveoschisis and foveal detachment. All patients received
      an intravitreal injection of 0.2-0.4 mL C3F8 and remained in the prone position
      for 5 to 7 days. The patients were followed up for at least 6 months after the
      procedure. The refractive status, best-corrected visual acuity (BCVA), fundus
      changes, premacular disorders, and anatomical results before and after the
      treatment were assessed and recorded. All participants underwent serial optical
      coherence tomography (OCT). RESULTS: All patients had myopia of more than -7
      diopters in the lesion eye. Staphyloma with chorioretinal atrophy was noted in
      all 10 eyes. The best-corrected visual acuity (BCVA) ranged from logMAR 0.52-2.0
      before treatment. After initial gas tamponade, foveal detachment had resolved
      completely in four eyes and partially in four eyes at the 1-month follow-up
      visit, and two of the partially resolved cases achieved anatomical success after
      repeated treatment. Another eye achieved reattachment 15 months later and the
      other had a persistent but decreased level of detachment. Vitrectomy was
      subsequently performed in the one eye that showed increased detachment, and
      complete resolution of the schisis-detachment was achieved. The final BCVA
      improved in seven eyes and none of the study subjects showed decreased visual
      acuity. CONCLUSION: Gas tamponade is an alternative treatment for myopic
      foveoschisis with foveal detachment. More than 50 % cases showed a positive
      response with increased visual acuity. Further, the procedure did not appear to
      interfere with subsequent vitrectomy, if this procedure must be performed.

PMID- 23142992
TI  - Cue reactivity in non-daily smokers: effects on craving and on smoking behavior.
AB  - RATIONALE: Non-daily, or intermittent smokers (ITS), are increasingly prevalent.
      Their smoking may be more situational than that of daily smokers (DS), and thus
      is hypothesized to be more influenced by cues. OBJECTIVES: To assess ITS'
      response to cues, and compare it to that of DS. METHODS: Samples of 239 ITS and
      207 DS (previously reported in Shiffman et al. 2012a) were studied in 2,586
      laboratory cue-reactivity sessions. Craving (Questionnaire of Smoking Urges) and
      smoking (probability, latency, puff parameters, and carbon monoxide increases) in
      response to cues was assessed following exposure to neutral cues and cues related
      to smoking, alcohol, negative affect, positive affect, and smoking prohibitions.
      Mixed effects models, generalized estimating equations and random-effects
      survival analyses were used to assess response to cues and differences between DS
      and ITS. RESULTS: ITS' craving increased following exposure to smoking and
      alcohol cues and decreased following positive affect cues, but cues had little
      effect on smoking behaviors. Cue reactivity was similar in ITS and DS. Among ITS,
      craving intensity predicted smoking probability, latency, and intensity, and the
      effects on latency were stronger among ITS than DS. CONCLUSIONS: Contrary to
      hypotheses, ITS were not more responsive to laboratory cues than DS. Results show
      that ITS do experience craving and craving increases that are then associated
      with smoking.

PMID- 23142993
TI  - Anterior chamber paracentesis and pH values in patients with acute primary angle
      closure.
AB  - BACKGROUND: To assess the efficacy and safety of anterior chamber paracentesis
      (ACP) and the changes in pH values in eyes with acute primary angle closure
      (APAC). METHODS: This retrospective case-control study involved 22 patients with
      APAC who underwent ACP (study group) and 21 patients with APAC who did not
      undergo ACP (control group). Intraocular pressure (IOP) and visual acuity were
      measured before treatment and 15 min and 24 h after treatment in both groups. The
      pH of aqueous humor was measured immediately after ACP in the study group.
      RESULTS: A total of 43 eyes in 43 patients were reviewed. The IOP 15 min after
      ACP (23.3 +/- 9.6 mmHg) and 24 h after ACP (21.6 +/- 12.0 mmHg) were
      significantly lower than that before ACP (58.6 +/- 12.9 mmHg). The IOP 15 min
      after ACP was significantly lower than the IOP 15 min after conventional
      treatment (55.4 +/- 10.3 mmHg). Visual acuity recovery was achieved earlier after
      ACP than after conventional treatment. Hyphema after ACP was noted in one eye.
      The mean pH of the aqueous humor in APAC was 6.99 +/- 0.35. The pH of the aqueous
      humor significantly correlated with the duration of acute IOP elevation and the
      IOP before ACP. CONCLUSIONS: ACP is an effective and safe procedure. The pH of
      aqueous humor is lower in eyes with APAC of longer duration and in eyes with
      higher IOP at presentation.

PMID- 23142994
TI  - Optical quality of the Visian Implantable Collamer Lens for different refractive
      powers.
AB  - PURPOSE: To evaluate the optical quality of the Visian Implantable Collamer Lens
      (ICL) for different powers and pupil diameters. METHODS: Wavefront aberrations of
      the -3, -6, -9, -12 and -15 diopters (D) V4b ICLs were measured at 3- and 4.5-mm
      pupils. The root mean square (RMS) of total higher order aberrations (HOAs),
      trefoil, coma, tetrafoil, secondary astigmatism, and spherical aberration were
      evaluated. In addition, modulation transfer function (MTF) of the five ICL powers
      was measured for a 3-mm pupil. The point spread functions (PSFs) of each ICL
      evaluated was calculated from the wavefront aberrations at 4.5-mm pupil. RESULTS:
      The ICLs evaluated had negative spherical aberration and negligible amounts of
      other aberrations. The negative spherical aberration increases when the ICL power
      increases being related with its innate optical properties. At 3-mm pupil, no
      statistically significant differences between ICLs were found for all the Zernike
      coefficient RMS values analyzed (p > 0.05). At 4.5-mm pupil, significant RMS
      values for the spherical aberration and total HOAs were found between medium-low
      and high powers (p < 0.05). Similar MTFs were obtained for all ICLs, although
      they slightly worsened when increased the ICL power. CONCLUSIONS: ICLs evaluated
      provide good optical quality in terms of wavefront aberrations, MTF, and PSF.
      Although spherical aberration increases with ICL power, these values are
      clinically negligible to affect the visual quality after its implantation.

PMID- 23142995
TI  - [Clinical diagnostics and surgical techniques in proctology].

PMID- 23142996
TI  - [Late complications following blunt abdominal and thoracic trauma: two case
      reports of a minimally invasive therapy].

PMID- 23142997
TI  - [Postoperative hypoparathyroidism: central neck dissection is a significant risk
      factor].

PMID- 23142998
TI  - [Outcome after laparoscopic versus open abdominoperineal resection for rectal
      cancer: results of a meta-analysis].

PMID- 23142999
TI  - [Elderly patients with gastrectomy: estimation of the outcome using the
      prognostic nutritional index].

PMID- 23143000
TI  - Early neurogenesis during caudal spinal cord regeneration in adult Gekko
      japonicus.
AB  - Gekko japonicus undergoes dramatic changes in the caudal spinal cord after tail
      amputation. The amputation induces cell proliferation in the caudal ependymal
      tube. We performed hematoxylin and eosin staining at different time points in the
      regeneration process to investigate the morphological characterization of the
      regenerated appendages. The central canal extended to the blastema post
      amputation and the cartilage and muscle tissue appeared 3 weeks after injury. We
      performed the bromodeoxyuridine (BrdU) incorporation assay to detect
      proliferating cells during the regeneration process. BrdU positive cells were
      detected in the peri-central canal. Furthermore, nestin and neuron-specific
      enolase (NSE) immunocytochemistry were applied to detect neural stem/progenitor
      cells and neurons. Two weeks after injury, nestin-positive cells undergoing
      proliferation were located outside of the ependymal tube, and NSE positive cells
      appeared after 3 weeks of amputation. These data suggest that neurogenesis is an
      early event during caudal spinal cord regeneration in gecko.

PMID- 23143001
TI  - Changes in the biological characteristics of glioma cancer stem cells after
      serial in vivo subtransplantation.
AB  - PURPOSE: Currently, the interaction between the niche and glioma cancer stem
      cells (gCSCs) is gaining attention. However, there are few studies concerned with
      the effects of repeated exposure to a new microenvironment on gCSCs
      characteristics. In this study, serial in vivo subtransplantation was performed
      to create a new microenvironment. We evaluated and compared the biological
      characteristics of gCSCs after serial in vivo subtransplantation. METHODS: We
      cultured gCSCs from human glioma specimens according to cultured gliomasphere
      methods. The isolated gCSCs were termed zero-generation gCSCs (G0-gCSCs). By
      subsequent serial subtransplantation, we obtained first-generation gCSCs (G1
      gCSCs) and second-generation gCSCs (G2-gCSCs). We evaluated and compared the
      biological characteristics of G0-gCSCs, G1-gCSCs, and G2-gCSCs. The in vitro
      characteristics included the morphology, surface marker profiles, and neural
      differentiation capacity and the in vivo characteristics was the survival of mice
      xenografts. Additionally, brain sections were analyzed using PCNA, TUNEL, and
      CD31 staining. RESULTS: We observed no significant differences in the in vitro
      characteristics of G0-gCSCs, G1-gCSCs, and G2-gCSCs. However, the survival time
      of mice glioma xenografts was significantly decreased upon serial
      subtransplantation. In addition, immunohistochemical analyses showed that the
      number of TUNEL(+) cells was significantly decreased while the number of CD31(+)
      cells was significantly increased with serial in vivo subtransplantation.
      CONCLUSIONS: There were significant in vivo biological changes in gCSCs upon
      serial in vivo subtransplantation, which were shorter xenograft survival,
      increased angiogenesis, and decreased apoptosis. This study suggests that the
      repeated exposure to new microenvironments may affect the biological changes in
      gCSCs in vivo.

PMID- 23143002
TI  - Isolation of glioma cancer stem cells in relation to histological grades in
      glioma specimens.
AB  - PURPOSE: The existence of cancer stem cells (CSCs) in glioblastoma has been
      proposed. However, the unknown knowledge that is yet to be revealed is the
      presence of glioma CSCs (gCSCs) in correlation to each WHO grades of glioma. We
      approached this study with a hypothesis that specimens from high-grade gliomas
      would have higher isolation rate of gCSCs in comparison to those of lower-grade
      gliomas. METHODS: The glioma specimens were obtained from patients and underwent
      gliomasphere assay. The gliomaspheres were chosen to be analyzed with
      immunocytochemisty for surface markers. Then the selected gliomaspheres were
      exposed to neural differentiation conditions. Lastly, we made mouse orthotopic
      glioma models to examine the capacity of gliomagenesis. RESULTS: The
      gliomaspheres were formed in WHO grade IV (13 of 21) and III (two of nine)
      gliomas. Among them, WHO grade IV (11 of 13) and III (two of two) gliomaspheres
      showed similar surface markers to gCSCs and were capable of neural
      differentiation. Lastly, among the chosen cells, 10 of 11 WHO grade IV and two of
      two WHO grade III gliomaspheres were capable of gliomagenesis. Thus, overall, the
      rates of existence of gCSCs were more prominent in high-grade gliomas: 47.6% (10
      of 21) in WHO grade IV gliomas and 22.2% (two of nine) in WHO grade III gliomas,
      whereas WHO grade II and I gliomas showed virtually no gCSCs. CONCLUSIONS: This
      trend of stage-by-stage increase of gCSCs in gliomas showed statistical
      significance by chi-square test linear-by-linear association. We prove that the
      rates of existence of gCSCs increase proportionally as the WHO grades of gliomas
      rise.

PMID- 23143003
TI  - Histone deacetylases expression in atypical teratoid rhabdoid tumors.
AB  - PURPOSE: Atypical teratoid rhabdoid tumors (ATRTs) are rare, highly malignant
      central nervous system tumors that occur during infancy and early childhood.
      Their poor outcome and resistance to conventional chemotherapies and
      radiotherapy, urges the development of new therapies. Recent studies have
      evaluated the effects of histone deacetylase inhibitors (HDACi) as a new
      potential treatment for ATRTs. However, most HDACi act unselectively against all,
      or at least several, histone deacetylase (HDAC) family members. We hypothesized
      that specific HDAC family members are deregulated in ATRT and therefore a more
      selective class of HDACi would be beneficial to patients with ATRT. METHODS: To
      test our hypothesis, we evaluated the expression level of different HDAC family
      members in ATRTs. Eight ATRTs were compared to six medulloblastoma samples in
      regards to the level of expression of the 18 HDAC family members as determined by
      microarray gene expression profiling. RESULTS: HDAC1 was the only member of the
      HDAC family to be significantly differentially expressed in ATRTs (FC = 4.728; p
      value = 0.00003). CONCLUSIONS: A class of HDACi specifically targeting HDAC1 may
      allow for the desired therapeutic benefits with fewer side effects for children
      with ATRT.

PMID- 23143004
TI  - Venous lacunae presenting with unusual upward protrusion: an anatomic study using
      high-resolution magnetic resonance imaging.
AB  - PURPOSE: This study aims to investigate the distribution and anatomic features of
      venous lacuna presenting with unusual upward protrusion (VLUUP) using high
      resolution magnetic resonance (MR) imaging. METHODS: This retrospective study
      included 59 consecutive outpatients who underwent MR imaging with gadolinium.
      Acquired imaging data were transferred to a workstation for analysis. RESULTS:
      The 30 male and 29 female subjects were aged from 10 to 76 years. A total of 46
      VLUUPs located parasagittally were identified in 36 of the 59 patients, 24 on the
      right, and 22 on the left; 29 patients had one VLUUP, 4 patients had two, and 3
      patients had three. Most VLUUPs (93 %) were distributed in the posterior third of
      the frontal region and the remainder (7 %) in the middle third. There were no
      VLUUP found in the anterior third of the frontal region or the parietal or
      occipital regions. The mean longitudinal and lateral dimensions of the VLUUPs and
      distance from the midline to the medial margin of the VLUUP were 9.7 mm (3.1
      27.6), 6.9 mm (3.1-11.5), and 14.3 mm (1.6-43.5), respectively. CONCLUSIONS: The
      VLUUPs carry a higher risk of injury when making a bony window in or involving
      the parasagittal posterior frontal region. High-resolution MR imaging is useful
      for delineating the VLUUPs.

PMID- 23143005
TI  - Ionic liquid-salt aqueous two-phase extraction based on salting-out coupled with
      high-performance liquid chromatography for the determination of sulfonamides in
      water and food.
AB  - Ionic liquid-salt aqueous two-phase extraction coupled with high-performance
      liquid chromatography with ultraviolet detection was developed for the
      determination of sulfonamides in water and food samples. In the procedure, the
      analytes were extracted from the aqueous samples into the ionic liquid top phase
      in one step. Three sulfonamides, sulfamerazine, sulfamethoxazole, and
      sulfamethizole were selected here as model compounds for developing and
      evaluating the method. The effects of various experimental parameters in
      extraction step were studied using two optimization methods, one variable at a
      time and Box-Behnken design. The results showed that the amount of sulfonamides
      did not have effect on the extraction efficiency. Therefore, a three-level Box
      Behnken experimental design with three factors, which combined the response
      surface modeling, was used to optimize sulfonamides extraction. Under the most
      favorable extraction parameters, the detection limits (S/N = 3) and
      quantification limits (S/N = 10) of the proposed method for the target compounds
      were achieved within the range of 0.15-0.3 ng/mL and 0.5-1.0 ng/mL from spiked
      samples, respectively, which are lower than or comparable with other reported
      approaches applied to the determination of the same compounds. Finally, the
      proposed method was successfully applied to the determination of sulfonamide
      compounds in different water and food samples and satisfactory recoveries of
      spiked target compounds in real samples were obtained.

PMID- 23143006
TI  - Electrode interfaces switchable by physical and chemical signals for biosensing,
      biofuel, and biocomputing applications.
AB  - This review outlines advances in designing modified electrodes with switchable
      properties controlled by various physical and chemical signals. Irradiation of
      the modified electrode surfaces with various light signals, changing the
      temperature of the electrolyte solution, application of a magnetic field or
      electrical potentials, changing the pH of the solutions, and addition of
      chemical/biochemical substrates were used to change reversibly the electrode
      activity. The increasing complexity in the signal processing was achieved by
      integration of the switchable electrode interfaces with biomolecular information
      processing systems mimicking Boolean logic operations, thus allowing activation
      and inhibition of electrochemical processes on demand by complex combinations of
      biochemical signals. The systems reviewed range from simple chemical compositions
      to complex mixtures modeling biological fluids, where the signal substrates were
      added at normal physiological and elevated pathological concentrations. The
      switchable electrode interfaces are considered for future biomedical applications
      where the electrode properties will be modulated by the biomarker concentrations
      reflecting physiological conditions.

PMID- 23143007
TI  - Intracellular in vitro probe acylcarnitine assay for identifying deficiencies of
      carnitine transporter and carnitine palmitoyltransferase-1.
AB  - Mitochondrial fatty acid oxidation (FAO) disorders are caused by defects in one
      of the FAO enzymes that regulates cellular uptake of fatty acids and free
      carnitine. An in vitro probe acylcarnitine (IVP) assay using cultured cells and
      tandem mass spectrometry is a tool to diagnose enzyme defects linked to most FAO
      disorders. Extracellular acylcarnitine (AC) profiling detects carnitine
      palmitoyltransferase-2, carnitine acylcarnitine translocase, and other FAO
      deficiencies. However, the diagnosis of primary carnitine deficiency (PCD) or
      carnitine palmitoyltransferase-1 (CPT1) deficiency using the conventional IVP
      assay has been hampered by the presence of a large amount of free carnitine (C0),
      a key molecule deregulated by these deficiencies. In the present study, we
      developed a novel IVP assay for the diagnosis of PCD and CPT1 deficiency by
      analyzing intracellular ACs. When exogenous C0 was reduced, intracellular C0 and
      total AC in these deficiencies showed specific profiles clearly distinguishable
      from other FAO disorders and control cells. Also, the ratio of intracellular to
      extracellular C0 levels showed a significant difference in cells with these
      deficiencies compared with control. Hence, intracellular AC profiling using the
      IVP assay under reduced C0 conditions is a useful method for diagnosing PCD or
      CPT1 deficiency.

PMID- 23143009
TI  - Conduction electron resonance used to determine size of palladium nanoparticles
      in proton conducting ceramics.
AB  - A technique for determining the size of metallic nanoparticles incorporated into
      a ceramic is demonstrated using conduction electron paramagnetic resonance
      (CEPR). The resonances associated with palladium nanoparticles in a perovskite
      material are identified and studied as a function of temperature. As this line
      shape changes with temperature, the point at which the skin depth of the
      palladium is the same as the size of the nanoparticles is clearly identified due
      to a microwave saturation effect. This allows for a determination of their
      average size, which, in this case is 75+/-20nm. This is the first example of CEPR
      being used to determine metallic nanoparticle size in a technologically relevant,
      embedded in a non EPR-inert material system.

PMID- 23143010
TI  - Spin-labelled cyclometallated palladium complexes. EPR study of dynamic processes
      in coordination sphere.
AB  - New four-, five- and six-coordinated cyclometallated o-semiquinonato palladium
      complexes were obtained and characterized in solution by EPR. Interaction of
      square-planar azaphenyl palladium semiquinonate with mono and bidentate phosphane
      donors leads to formation of five- and six-coordinated adducts. Typical values of
      HFC constants on apical and basal phosphorouses are observed for such compounds.
      In one case the reversible addition of tri-phenyl-phosphane was observed. The
      coordination mode of pincer ligand (bi- or tridentate) in o-semiquinonato pincer
      complexes depends on the nature of linker between coordinating group and pincer
      aryl ring. In the case of CH(2) linker five coordinated complexes are formed. The
      "swing" and "fan" oscillations are observed for these compounds. Complexes with 
      O- linker are the first examples of compounds with bidentate bonded phosphorous
      based pincer ligand. Most of complexes are unstable and decompose during some
      hours. Only the application of o-semiquinones as spin labels and using the EPR
      technique made possible to observe and interpret their structure.

PMID- 23143011
TI  - A rapid method for direct detection of metabolic conversion and magnetization
      exchange with application to hyperpolarized substrates.
AB  - In this work, we present a new MR spectroscopy approach for directly observing
      nuclear spins that undergo exchange, metabolic conversion, or, generally, any
      frequency shift during a mixing time. Unlike conventional approaches to observe
      these processes, such as exchange spectroscopy (EXSY), this rapid approach
      requires only a single encoding step and thus is readily applicable to
      hyperpolarized MR in which the magnetization is not replenished after T(1) decay
      and RF excitations. This method is based on stimulated-echoes and uses phase
      sensitive detection in conjunction with precisely chosen echo times in order to
      separate spins generated during the mixing time from those present prior to
      mixing. We are calling the method Metabolic Activity Decomposition Stimulated
      echo Acquisition Mode or MAD-STEAM. We have validated this approach as well as
      applied it in vivo to normal mice and a transgenic prostate cancer mouse model
      for observing pyruvate-lactate conversion, which has been shown to be elevated in
      numerous tumor types. In this application, it provides an improved measure of
      cellular metabolism by separating [1-(13)C]-lactate produced in tissue by
      metabolic conversion from [1-(13)C]-lactate that has flowed into the tissue or is
      in the blood. Generally, MAD-STEAM can be applied to any system in which spins
      undergo a frequency shift.

PMID- 23143012
TI  - Aquaporin-4 distribution in control and stressed astrocytes in culture and in the
      cerebrospinal fluid of patients with traumatic brain injuries.
AB  - Distribution of aquaporin-4 (AQP4) was studied by western analysis and
      immunofluorescence in rat astrocytes exposed to either hypothermic (30  degrees
      C) or hyperosmolar (0.45 M sucrose) stress, and in the cerebrospinal fluid (CSF)
      of patients who suffered traumatic brain injury (TBI). CSF was obtained from 5
      healthy subjects and from 20 patients suffering from severe TBI. CSF samples were
      taken at admission and on days 3 and 5-7. Here we report that, in response to
      both hypothermia and hyperosmolar stress, AQP4 was markedly reduced in cultured
      astrocytes. We also found that AQP4 significantly increased in patients with
      severe brain injury in respect to healthy subjects (P < 0.002). AQP4 in CSF
      remained unchanged in patients with elevated intracranial pressure (ICP), whereas
      there was a clear tendency to further increase in those patients whose ICP could
      be controlled within the normal range. We conclude that AQP4 levels in CSF are
      elevated after TBI and it might serve as a useful biochemical marker to assess
      brain water metabolism in clinical settings.

PMID- 23143013
TI  - Delayed anesthetic preconditioning protects against myocardial infarction via
      activation of nuclear factor-kappaB and upregulation of autophagy.
AB  - PURPOSE: Delayed volatile anesthetic preconditioning (APC) can protect against
      myocardial ischemia/reperfusion (I/R) injury; the delayed phase is called the
      second window of protection (SWOP), but the underlying mechanism is unclear.
      Nuclear factor-kappaB (NF-kappaB) is involved in the myocardial protection
      conferred by APC in the acute phase; autophagy has been reported to confer
      apoptosis inhibition and infarction reduction. We hypothesized that APC initiates
      delayed cardioprotection against I/R injury via the activation of NF-kB and
      upregulation of autophagy, thus attenuating the inflammatory response and
      apoptosis METHODS: After a rat I/R model was set up, left ventricular samples
      were obtained before I/R to assess NF-kappaB-DNA binding activity and microtubule
      associated protein 1 light chain 3 (LC3) and cathepsin B protein expression, and
      to examine autophagosomes with a transmission electron microscope. Infarct size
      and the expressions of tumor necrosis factor alpha (TNF-alpha), interleukin 1beta
      (IL-1beta), and caspase-3 were measured at the end of 2-h reperfusion. RESULTS:
      The infarct size was significantly reduced in the SWOP group (30 +/- 3 %) when
      compared with that in the I/R group (47 +/- 7 %, P < 0.05), and this finding was
      associated with increased NF-kappaB-DNA binding activity and autophagosomes. In
      addition, the expressions of LC3-II and cathepsin B were also up-regulated, and
      the expressions of TNF-alpha, IL-1beta, and caspase-3 were attenuated in the SWOP
      group when compared with the findings in the I/R group. However, this protection
      was abolished by the administration of parthenolide (PTN) before sevoflurane
      inhalation, which resulted in an infarct size that was significantly increased
      (47 +/- 5 %, P < 0.05 PTN + SWOP vs. SWOP group). CONCLUSION: Delayed APC
      protected the rat heart from I/R injury. The underlying mechanisms may include NF
      kappaB activation, upregulation of autophagy, and the attenuation of TNF-alpha,
      IL-1beta, and caspase-3 expressions.

PMID- 23143014
TI  - Large physisorption strain and edge modification of Pd on monolayer graphene.
AB  - Using Raman spectroscopic studies, we firstly report that Pd film deposition can
      induce a tensile strain at the interface between Pd and n-layer graphenes, which
      results in the splitting of the G peak and a red Raman shift of the 2D peak in
      monolayer graphene, and red Raman shifts of G and 2D peaks for other n-layer
      graphenes. In particular, this kind of tensile strain can be used as an effective
      way for edge modification or strain engineering in monolayer graphene.

PMID- 23143015
TI  - The utility of ultrasound imaging in predicting ease of performance of spinal
      anesthesia in an orthopedic patient population.
AB  - BACKGROUND AND OBJECTIVES: Ultrasonography of the spine improves technical
      performance of spinal anesthesia, but what is unclear is whether it can predict
      difficulty. We tested the hypothesis that a good ultrasound view at a given
      intervertebral level is associated with absence of technical difficulty. METHODS:
      We performed preprocedural ultrasound of the L1-S1 intervertebral spaces in 100
      patients undergoing orthopedic surgery. Visibility of the ligamentum flavum-dura
      mater and the posterior longitudinal ligament was evaluated using paramedian
      sagittal oblique and transverse midline (TM) views. Views were classified as good
      if both of these structures were visible on ultrasound. An operator, blinded to
      the ultrasound scan, performed surface landmark-guided spinal anesthesia using a
      midline approach. Absence of technical difficulty was defined as successful dural
      puncture within 2 skin punctures or 10 needle passes. RESULTS: A good TM view had
      the best diagnostic accuracy; if this view was obtained, absence of technical
      difficulty with dural puncture at that level was highly likely (positive
      predictive value, 85%). Dural puncture could still be feasible despite the
      absence of a good TM view, as reflected by a negative predictive value of 30%.
      This was attributed to the limitations of ultrasound imaging in this patient
      population, as well as the low overall prevalence of difficult dural puncture.
      Parasagittal oblique views did not have significant diagnostic utility for a
      midline needle approach. CONCLUSIONS: Ultrasound can be useful in predicting the
      absence of technical difficulty in performing dural puncture and thus in
      selecting the optimal intervertebral level for spinal anesthesia.

PMID- 23143016
TI  - Comparison of two methods for the estimation of subcortical volume and asymmetry
      using magnetic resonance imaging: a methodological study.
AB  - PURPOSE: The subcortical brain structures are associated with other structures of
      nervous system; therefore, they have major influence on sensory-motor, limbic and
      cognitive information processing. Magnetic resonance imaging provides a detailed
      knowledge of normal and diseased anatomical structures for medical research. The
      aim of the current study was to compare the volumes of subcortical brain
      structures and determine the probable volumetric asymmetry in healthy subjects
      using stereological (point-counting) and semi-automatic segmentation methods.
      METHODS: MR scans were obtained from 30 subjects (17 males, 13 females) free of
      any psychiatric, neurological or cognitive impairment. MR images were analyzed by
      using stereological (point-counting) and semi-automatic segmentation methods.
      RESULTS: We did not find any significant differences among the subjects with
      respect to gender using both methods. This study showed no significant asymmetry
      in subcortical structures according to methods. Also, no significant difference
      was found between point-counting and semi-automated segmentation methods for the
      volumes of subcortical structures (p > 0.05). CONCLUSION: From these results, it
      can be concluded that the semi-automated segmentation method and stereological
      technique can be used for reliable volume estimation of subcortical structures.
      However, the stereological method takes less time than semi-automated
      segmentation; it is simple, reliable and inexpensive. Further studies are
      required with larger samples in order to support these data.

PMID- 23143017
TI  - The role of the anatomy of the sigmoid colon in developing sigmoid volvulus: a
      cross-sectional study.
AB  - PURPOSE: The aim of this study was to determine the length of the sigmoid colon
      and sigmoid mesocolon in living subjects and fresh cadavers. METHODS: The
      subjects for the study were consecutive 50 living subjects undergoing abdominal
      surgeries via midline incision and 50 fresh cadavers undergoing a medicolegal
      postmortem at Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife,
      Osun State, Nigeria. RESULTS: The study showed that the mean length of the
      sigmoid colon in living subjects was 48.9 +/- 1.3 cm (range 30.5-65 cm) while the
      mean length of the sigmoid colon in cadaver subjects was 50.1 +/- 1.6 cm (range
      34.5-67.8 cm) and this was not statistically significantly different. Two
      patterns of the shape of the sigmoid loop were identified: dolichomesocolic and
      brachymesocolic pattern. In about 80 % of subjects in both groups,
      dolichomesocolic-type was seen. The gender analysis showed that males had
      statistically significant longer sigmoid colon (P = 0.040). The dimension of
      sigmoid colon significantly increased with age of the patients in cadaver
      subjects and in both sexes (P = 0.001). CONCLUSIONS: The study concluded that the
      lengths of sigmoid colon are not different in living and cadaver subjects but are
      relatively longer than measurement from western countries. The lengths of sigmoid
      colon and mesocolon also increases with age and this may possibly be the
      anatomical basis for the frequent occurrence of sigmoid volvulus and failed
      colonoscopy among the older population in our environment.

PMID- 23143018
TI  - Structure determination of functional membrane proteins using small-angle neutron
      scattering (sans) with small, mixed-lipid liposomes: native beef heart
      mitochondrial cytochrome c oxidase forms dimers.
AB  - The low-resolution three-dimensional structure of purified native beef heart
      mitochondrial cytochrome c oxidase (COX) in asolectin unilamellar liposomes has
      been measured by small-angle neutron scattering under the conditions where the
      protein remains fully functional. From a neutron scattering perspective, the use
      of mixed-lipid liposomes provided for a more homogeneous matrix than can be
      achieved using a single lipid. As a result, the measurements were able to be
      performed under conditions where the liposome scattering was essentially
      eliminated (contrast-matched conditions). The protein structure in the membrane
      was modeled as a simple parallelepiped with side lengths of (59 * 70 * 120) A
      with uncertainties, respectively, (11, 12, 20 A). The molecular mass calculated
      for a typical protein with this volume is estimated to be (410 +/- 124) kDa,
      which indicates the mass of a COX dimer. The longest dimension has some
      uncertainty due to intermolecular scattering contributing to the data.
      Nevertheless, that length was estimated using an average protein density and the
      known dimer molecular mass. Using the same cross sectional dimensions for the
      structure, the length is estimated to be 120 A. However, the measured scattering
      curve of the dimer in the liposome differs significantly from that calculated
      from the X-ray structure of the dimer in a crystal of mixed micelles (PDB 3AG1).
      The calculated SANS scattering from the crystal structure was fit with a
      parallelepiped, measuring (59 * 101 * 129) A with fitting uncertainties,
      respectively, (2, 3, 3 A). Our results suggest that COX is a functional dimer
      when reconstituted into mixed-lipid liposomes.

PMID- 23143019
TI  - Nitrosyl isomerism in amorphous Mn(TPP)(NO) solids.
AB  - Reaction of NO with amorphous Mn(TPP) layers gives two Mn(TPP)(NO) isomers with
      linear and bent Mn-N-O geometries that reversibly interconvert with changes in
      temperature. DFT computations predict that the linear complex is the singlet
      ground state while the bent structure is a triplet state.

PMID- 23143020
TI  - Age-related apparent diffusion coefficient changes in the normal brain.
AB  - PURPOSE: To measure the mean diffusional age-related changes of the brain over
      the full human life span by using diffusion-weighted spin-echo single-shot echo
      planar magnetic resonance (MR) imaging and sequential whole-brain apparent
      diffusion coefficient (ADC) histogram analysis and, secondarily, to build
      mathematical models of these normal age-related changes throughout human life.
      MATERIALS AND METHODS: After obtaining institutional review board approval, a
      HIPAA-compliant retrospective search was conducted for brain MR imaging studies
      performed in 2007 for various clinical indications. Informed consent was waived.
      The brain data of 414 healthy subjects (189 males and 225 females; mean age, 33.7
      years; age range, 2 days to 89.3 years) were obtained with diffusion-weighted
      spin-echo single-shot echo-planar MR imaging. ADC histograms of the whole brain
      were generated. ADC peak values, histogram widths, and intracranial volumes were
      plotted against age, and model parameters were estimated by using nonlinear
      regression. RESULTS: Four different stages were identified for aging changes in
      ADC peak values, as characterized by specific mathematical terms: There were age
      associated exponential decays for the maturation period and the development
      period, a constant term for adulthood, and a linear increase for the senescence
      period. The age dependency of ADC peak value was simulated by using four-term six
      coefficient function, including biexponential and linear terms. This model fit
      the data very closely (R(2) = 0.91). CONCLUSION: Brain diffusivity as a whole
      demonstrated age-related changes through four distinct periods of life. These
      results could contribute to establishing an ADC baseline of the normal brain,
      covering the full human life span.

PMID- 23143021
TI  - Peripheral arterial occlusive disease: 3.0-T versus 1.5-T MR angiography compared
      with digital subtraction angiography.
AB  - PURPOSE: To prospectively evaluate the diagnostic accuracy of 3-T versus 1.5-T
      contrast material-enhanced (CE) magnetic resonance (MR) angiography with high
      spatial resolution in patients who have peripheral arterial occlusive disease,
      with conventional digital subtraction angiography (DSA) serving as the reference
      standard. MATERIALS AND METHODS: Institutional review board approval and written
      informed consent were obtained. DSA and standardized single-injection, three
      station, moving-table CE MR angiography, with similar acquisition protocols and
      contrast agent doses at 3 T and 1.5 T, were consecutively performed in 19
      patients (13 men and six women; mean age +/- standard deviation, 67 years +/- 9).
      Stenosis was scored visually in 500 arterial segments (97.5% of all available) in
      consensus by two radiologists in a blinded manner (the radiologists were unaware
      of the field strength and prior DSA and MR angiographic results and used
      randomized analysis order). Contrast-to-noise ratio was determined in the
      vascular tree of both legs. Statistical significance in stenosis scoring was
      evaluated by using generalized estimating equations. Contrast-to-noise
      differences were evaluated with paired t tests. Agreement between MR angiography
      and DSA was evaluated by using Fleiss-Cohen kappa statistics. RESULTS: Both 3-T
      and 1.5-T CE MR angiography showed similar excellent agreement with DSA regarding
      stenosis classification (kappa = 0.96 and 0.93, respectively). All sensitivity
      and specificity values exceeded 90%. Mean contrast-to-noise ratio was 3.0-4.2
      times higher at 3 T than at 1.5 T. CONCLUSION: Standardized single-injection,
      three-station, moving-table 3-T CE MR angiography is reliable for classification
      of stenosis in patients suspected of having peripheral arterial occlusive
      disease, and diagnostic performance was similar to that seen with 1.5-T MR
      angiography. There was a significantly increased contrast-to-noise ratio for
      identical contrast agent dose at 3-T MR angiography.

PMID- 23143022
TI  - Carotid artery stenosis: wide variability in reporting formats--a review of 127
      Veterans Affairs medical centers.
AB  - PURPOSE: To determine whether radiology reports describe clinically significant
      carotid arterial stenosis in a consistent format that is actionable by ordering
      clinicians. MATERIALS AND METHODS: This study was HIPAA compliant. Informed
      consent was waived. Institutional review board approval was obtained for this
      retrospective chart review, which included radiology reports of carotid artery
      imaging for patients hospitalized with ischemic stroke at 127 Veterans Affairs
      medical centers in 2006-2007. "Clinically significant results" were defined as
      results with at least 50% stenosis or at least moderate stenosis, excluding
      complete occlusion. How often clinically significant results were reported as an
      exact percentage stenosis (such as 60%), range (such as 50%-69%), or category
      (such as moderate) was determined. Among results reported as a range, how often
      the range bracketed clinical thresholds of 50% and 70% (typically used to
      determine appropriateness of carotid arterial revascularization) was determined.
      RESULTS: Among 2675 patients, there were 6618 carotid imaging results, of which
      1015 (15%) were considered clinically significant. Among 695 clinically
      significant results at ultrasonography (US), 348 (50%) were described as a range,
      and another 314 (45%) were reported as an exact percentage stenosis. Among the
      348 clinically significant US results reported as a range, 259 (74%) bracketed
      the thresholds of 50% or 70%. For magnetic resonance angiographic results, 48%
      (106 of 221) qualitatively described clinically significant results as a
      category, 38% (84 of 221) as an exact percentage stenosis, and 14% (31 of 221) as
      a range. CONCLUSION: In this national health care system, the manner in which
      clinically significant carotid arterial stenosis was reported varied widely.

PMID- 23143023
TI  - Digital breast tomosynthesis versus supplemental diagnostic mammographic views
      for evaluation of noncalcified breast lesions.
AB  - PURPOSE: To compare the diagnostic performance of breast tomosynthesis versus
      supplemental mammography views in classification of masses, distortions, and
      asymmetries. MATERIALS AND METHODS: Eight radiologists who specialized in breast
      imaging retrospectively reviewed 217 consecutively accrued lesions by using
      protocols that were HIPAA compliant and institutional review board approved in
      182 patients aged 31-60 years (mean, 50 years) who underwent diagnostic
      mammography and tomosynthesis. The lesions in the cohort included 33% (72 of 217)
      cancers and 67% (145 of 217) benign lesions. Eighty-four percent (182 of 217) of
      the lesions were masses, 11% (25 of 217) were asymmetries, and 5% (10 of 217)
      were distortions that were initially detected at clinical examination in 8% (17
      of 217), at mammography in 80% (173 of 217), at ultrasonography (US) in 11% (25
      of 217), or at magnetic resonance imaging in 1% (2 of 217). Histopathologic
      examination established truth in 191 lesions, US revealed a cyst in 12 lesions,
      and 14 lesions had a normal follow-up. Each lesion was interpreted once with
      tomosynthesis and once with supplemental mammographic views; both modes included
      the mediolateral oblique and craniocaudal views in a fully crossed and balanced
      design by using a five-category Breast Imaging Reporting and Data System (BI
      RADS) assessment and a probability-of-malignancy score. Differences between modes
      were analyzed with a generalized linear mixed model for BI-RADS-based sensitivity
      and specificity and with modified Obuchowski-Rockette approach for probability-of
      malignancy-based area under the receiver operating characteristic (ROC) curve.
      RESULTS: Average probability-of-malignancy-based area under the ROC curve was
      0.87 for tomosynthesis versus 0.83 for supplemental views (P < .001). With
      tomosynthesis, the false-positive rate decreased from 85% (989 of 1160) to 74%
      (864 of 1160) (P < .01) for cases that were rated BI-RADS category 3 or higher
      and from 57% (663 of 1160) to 48% (559 of 1160) for cases rated BI-RADS category
      4 or 5 (P < .01), without a meaningful change in sensitivity. With tomosynthesis,
      more cancers were classified as BI-RADS category 5 (39% [226 of 576] vs 33% [188
      of 576]; P = .017) without a decrease in specificity. CONCLUSION: Tomosynthesis
      significantly improved diagnostic accuracy for noncalcified lesions compared with
      supplemental mammographic views.

PMID- 23143024
TI  - Validation and initial clinical use of automatic peak skin dose localization with
      fluoroscopic and interventional procedures.
AB  - PURPOSE: To assess the accuracy and initial clinical use of a software tool that
      automatically maps and records values of skin dose, including peak skin dose
      (PSD), administered to patients undergoing fluoroscopically guided interventional
      procedures. MATERIALS AND METHODS: In this retrospective study, the institutional
      review board determined that this HIPAA-compliant study met the criteria as a
      quality assurance investigation. Informed consent was waived. After the initial
      validation and accuracy tests, distributed skin dose and PSD estimates were
      obtained for fluoroscopically guided interventional procedures performed in the
      radiology, cardiology, and gastroenterology practice areas between January and
      October 2011. A total of 605 procedures were performed in 520 patients (64% men;
      age range, 20-95 years). The accuracy of a skin dose tool to estimate patient
      dose distribution was verified with phantom studies by using an external
      dosimeter and direct exposure film. PSD distribution, PSD according to procedure
      type, and PSD for individual physician operators were assessed. RESULTS:
      Calculated PSD values agreed within +/-9% of that measured by using film
      dosimetry under the condition of matched-phantom geometry. The area receiving the
      highest dose (greater than 95% of peak) agreed within +/-17%. Of 605 patient
      procedures, 15 demonstrated PSD greater than 2 Gy, with a maximum PSD of 5.6 Gy.
      CONCLUSION: Knowledge of the patient skin dose can help direct treatment of
      patients who were administered relatively high skin dose and may be used to plan
      future procedures. SUPPLEMENTAL MATERIAL:
      http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12112295/-/DC1.

PMID- 23143025
TI  - Quantification of muscle fat in patients with low back pain: comparison of multi
      echo MR imaging with single-voxel MR spectroscopy.
AB  - PURPOSE: To compare lumbar muscle fat-signal fractions derived from three
      dimensional dual gradient-echo magnetic resonance (MR) imaging and multiple
      gradient-echo MR imaging with fractions from single-voxel MR spectroscopy in
      patients with low back pain. MATERIALS AND METHODS: This prospective study had
      institutional review board approval, and written informed consent was obtained
      from all study participants. Fifty-six patients (32 women; mean age, 52 years +/-
      15 [standard deviation]; age range, 20-79 years) with low back pain underwent
      standard 1.5-T MR imaging, which was supplemented by dual-echo MR imaging, multi
      echo MR imaging, and MR spectroscopy to quantify fatty degeneration of bilateral
      lumbar multifidus muscles in a region of interest at the intervertebral level of
      L4 through L5. Fat-signal fractions were determined from signal intensities on
      fat- and water-only images from both imaging data sets (dual-echo and multi-echo
      fat-signal fractions without T2* correction) or directly obtained, with
      additional T2* correction, from multi-echo MR imaging. The results were compared
      with MR spectroscopic fractions. The Student t test and Bland-Altman plots were
      used to quantify agreement between fat-signal fractions derived from imaging and
      from spectroscopy. RESULTS: In total, 102 spectroscopic measurements were
      obtained bilaterally (46 of 56) or unilaterally (10 of 56). Mean spectroscopic
      fat-signal fraction was 19.6 +/- 11.4 (range, 5.4-63.5). Correlation between
      spectroscopic and all imaging-based fat-signal fractions was statistically
      significant (R(2) = 0.87-0.92; all P < .001). Mean dual-echo fat-signal fractions
      not corrected for T2* and multi-echo fat-signal fractions corrected for T2*
      significantly differed from spectroscopic fractions (both P < .01), but mean
      multi-echo fractions not corrected for T2* did not (P = .11). There was a small
      measurement bias of 0.5% (95% limits of agreement: -6.0%, 7.2%) compared with
      spectroscopic fractions. CONCLUSION: Large-volume image-based (dual-echo and
      multi-echo MR imaging) and spectroscopic fat-signal fractions agree well, thus
      allowing fast and accurate quantification of muscle fat content in patients with
      low back pain.

PMID- 23143026
TI  - Findings of the UK national audit evaluating image-guided or image-assisted liver
      biopsy. Part II. Minor and major complications and procedure-related mortality.
AB  - PURPOSE: To determine the frequency of complications and death following image
      guided and/or image-assisted liver biopsy and to identify significant variables
      associated with an increased risk of complications or death. MATERIALS AND
      METHODS: Institutional review board approval for this type of study is not
      required in the United Kingdom. United Kingdom radiology departments with a
      department leader for audit registered with the Royal College of Radiologists
      were invited to participate. The first 50 consecutive patients who underwent
      liver biopsy in 2008 were included. Audit standards were developed for minor pain
      (<30%), severe pain (<3%), vasovagal hypotension (<3%), significant hemorrhage
      (<0.5%), hemobilia (<0.1%), puncture of another organ (<0.1%), and death (<0.1%).
      Organizational, clinical, and coagulation variables were investigated
      statistically for their association with complications and/or death. RESULTS:
      Data were obtained from 87 of 210 departments (41%). Audit standards were met for
      pain, hypotension, hemorrhage, hemobilia, and puncture of another organ. There
      were four hemorrhage-related deaths, and this target was narrowly missed (rate
      achieved in practice, 0.11% [four of 3486 patients]). Fifteen additional patients
      experienced at least one major complication. The international normalized ratio
      (INR) was absent in 3% of cases (97 of 2951 patients), the platelet count was
      absent in 1% (32 of 2986 patients), the INR was more than 1 week old in 8% (229
      of 2888 patients), and the platelet count was more than 1 week old in 10% (291 of
      2955 patients). CONCLUSION: Results of this audit confirm that image-guided and
      image-assisted biopsy is performed safely in United Kingdom radiology
      departments, with complication rates within expected parameters. Preprocedural
      clotting assessment was inadequate in some cases and would merit repeat audit.
      SUPPLEMENTAL MATERIAL:
      http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120224/-/DC1.

PMID- 23143027
TI  - Intraprocedural C-arm dual-phase cone-beam CT: can it be used to predict short
      term response to TACE with drug-eluting beads in patients with hepatocellular
      carcinoma?
AB  - PURPOSE: To investigate whether C-arm dual-phase cone-beam computed tomography
      (CT) performed during transcatheter arterial chemoembolization (TACE) with
      doxorubicin-eluting beads can help predict tumor response at 1-month follow-up in
      patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This
      prospective study was compliant with HIPAA and approved by the institutional
      review board and animal care and use committee. Analysis was performed
      retrospectively on 50 targeted HCC lesions in 29 patients (16 men, 13 women; mean
      age, 61.9 years +/- 10.7) treated with TACE with drug-eluting beads. Magnetic
      resonance (MR) imaging was performed at baseline and 1 month after TACE. Dual
      phase cone-beam CT was performed before and after TACE. Tumor enhancement at dual
      phase cone-beam CT in early arterial and delayed venous phases was assessed
      retrospectively with blinding to MR findings. Tumor response at MR imaging was
      assessed according to European Association for the Study of the Liver (EASL)
      guidelines. Two patients were excluded from analysis because dual-phase cone-beam
      CT scans were not interpretable. Logistic regression models for correlated data
      were used to compare changes in tumor enhancement between modalities. The
      radiation dose with dual-phase cone-beam CT was measured in one pig. RESULTS: At
      1-month MR imaging follow-up, complete and/or partial tumor response was seen in
      74% and 76% of lesions in the arterial and venous phases, respectively. Paired t
      tests used to compare images obtained before and after TACE showed a significant
      reduction in tumor enhancement with both modalities (P < .0001). The decrease in
      tumor enhancement seen with dual-phase cone-beam CT after TACE showed a linear
      correlation with MR findings. Estimated correlation coefficients were excellent
      for first (R = 0.89) and second (R = 0.82) phases. A significant relationship
      between tumor enhancement at cone-beam CT after TACE and complete and/or partial
      tumor response at MR imaging was found for arterial (odds ratio, 0.95; 95%
      confidence interval [CI]: 0.91, 0.99; P = .023) and venous (odds ratio, 0.96; 95%
      CI: 0.93, 0.99; P = .035) phases with the multivariate logistic regression model.
      Radiation dose for two dual-phase cone-beam CT scans was 3.08 mSv. CONCLUSION:
      Intraprocedural C-arm dual-phase cone-beam CT can be used immediately after TACE
      with doxorubicin-eluting beads to predict HCC tumor response at 1-month MR
      imaging follow-up.

PMID- 23143028
TI  - Percutaneous recanalization for Budd-Chiari syndrome: an 11-year retrospective
      study on patency and survival in 177 Chinese patients from a single center.
AB  - PURPOSE: To evaluate the long-term outcomes of percutaneous recanalization and
      determine the predictors of patency and survival in a large case series of
      Chinese patients with Budd-Chiari syndrome (BCS). MATERIALS AND METHODS: This
      retrospective study was approved by the institutional ethics committee. Informed
      consent for the procedure was obtained from all patients. Between July 1999 and
      August 2010, 177 consecutive Chinese patients with primary BCS were treated with
      percutaneous recanalization and followed up until death or their last clinical
      evaluation. Recanalization therapeutic strategy and complications were recorded.
      Cumulative patency and survival rates were assessed with Kaplan-Meier curves.
      Independent predictors of patency and survival were calculated with the Cox
      regression model. RESULTS: Percutaneous recanalization was technically successful
      in 168 of the 177 patients (95%). Fifty-one of the 168 patients (30%) were
      treated with percutaneous transluminal angioplasty (PTA) alone and 117 (70%) were
      treated with a combination of PTA and stent placement. Procedure-related
      complications occurred in seven of the 168 patients (4%). The cumulative 1-, 5-,
      and 10-year primary patency rates were 95%, 77%, and 58%, respectively.
      Independent predictors of reocclusion included increased white blood cell count
      and use of PTA alone. The cumulative 1-, 5-, and 10-year secondary patency rates
      were 97%, 90%, and 86%, respectively. Twenty-two patients died during a median
      follow-up of 30 months (range, 0.25-137 months). The cumulative 1-, 5-, and 10
      year survival rates were 96%, 83%, and 73%, respectively. Independent predictors
      of survival included variceal bleeding, increased alkaline phosphatase and blood
      urea nitrogen levels, and reocclusion. CONCLUSION: Percutaneous recanalization
      could achieve excellent long-term patency and survival in most Chinese patients
      with BCS. PTA combined with stent placement should be recommended to decrease the
      frequency of reocclusion and its associated mortality.

PMID- 23143029
TI  - Transition zone prostate cancer: detection and localization with 3-T
      multiparametric MR imaging.
AB  - PURPOSE: To retrospectively compare transition zone (TZ) cancer detection and
      localization accuracy of 3-T T2-weighted magnetic resonance (MR) imaging with
      that of multiparametric (MP) MR imaging, with radical prostatectomy specimens as
      the reference standard. MATERIALS AND METHODS: The informed consent requirement
      was waived by the institutional review board. Inclusion criteria were radical
      prostatectomy specimen TZ cancer larger than 0.5 cm(3) and 3-T endorectal
      presurgery MP MR imaging (T2-weighted imaging, diffusion-weighted [DW] imaging
      apparent diffusion coefficient [ADC] maps [b < 1000 sec/mm(2)], and dynamic
      contrast material-enhanced [DCE] MR imaging). From 197 patients with radical
      prostatectomy specimens, 28 patients with TZ cancer were included. Thirty-five
      patients without TZ cancer were randomly selected as a control group. Four
      radiologists randomly scored T2-weighted and DW ADC images, T2-weighted and DCE
      MR images, and T2-weighted, DW ADC, and DCE MR images. TZ cancer suspicion was
      rated on a five-point scale in six TZ regions of interest (ROIs). A score of 4-5
      was considered a positive finding. A score of 4 or higher for any ROI containing
      TZ cancer was considered a positive detection result at the patient level.
      Generalized estimating equations were used to analyze detection and localization
      accuracy by using ROI-receiver operating characteristics (ROC) curve analyses for
      the latter. Gleason grade (GG) 4-5 and GG 2-3 cancers were analyzed separately.
      RESULTS: Detection accuracy did not differ between T2-weighted and MP MR imaging
      for all TZ cancers (68% vs 66%, P = .85), GG 4-5 TZ cancers (79% vs 72%-75%, P =
      .13), and GG 2-3 TZ cancers (66% vs 62%-65%, P = .47). MP MR imaging (area under
      the ROC curve, 0.70-0.77) did not improve T2-weighted imaging localization
      accuracy (AUC = 0.72) (P > .05). CONCLUSION: Use of 3-T MP MR imaging, consisting
      of T2-weighted imaging, DW imaging ADC maps (b values, 50, 500, and 800
      sec/mm(2)), and DCE MR imaging may not improve TZ cancer detection and
      localization accuracy compared with T2-weighted imaging. SUPPLEMENTAL MATERIAL:
      http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120281/-/DC1.

PMID- 23143030
TI  - Transcription factor CREB is phosphorylated in human molar odontoblasts and
      cementoblasts in vivo.
AB  - A wide variety of stimuli can trigger activation of the transcription factor CREB
      (cAMP-responsive element binding protein), pointing toward a central role for
      CREB in the integration of various signaling inputs. No data are available on the
      expression and phosphorylation of CREB in mammalian teeth. Using
      immunohistochemical analysis of free-floating sections, we show here that CREB
      was strongly expressed and phosphorylated at Ser-133 within the nucleus of a
      subpopulation of adult human molar odontoblasts. Many dental pulp stromal cells
      and periodontal ligament fibroblasts expressed CREB and showed phosphorylation of
      CREB at Ser-133. In addition, cementoblasts displayed nuclear expression and
      phosphorylation of CREB at Ser-133. The epithelial rests of Malassez revealed
      strong nuclear expression of CREB, but phosphorylation at Ser-133 was variable.
      Our results provide the first evidence that the constitutively phosphorylated
      transcription factor CREB is involved in the biomineralization process of adult
      human molar odontoblasts and cementoblasts.

PMID- 23143031
TI  - [The pelvis].

PMID- 23143032
TI  - [Treatment of periprosthetic and peri-implant fractures : modern plate
      osteosynthesis procedures].
AB  - Periprosthetic fractures are increasing not only due to the demographic
      development with high life expectancy, the increase in osteoporosis and increased
      prosthesis implantation but also due to increased activity of the elderly
      population. The therapeutic algorithms are manifold but general valid rules for
      severe fractures are not available. The most commonly occurring periprosthetic
      fractures are proximal and distal femoral fractures but in the clinical routine
      fractures of the tibial head, ankle, shoulder, elbow and on the borders to other
      implants (peri-implant fractures) and complex interprosthetic fractures are being
      seen increasingly more. It is to be expected that in the mid-term further
      options, such as cement augmentation of cannulated polyaxial locking screws will
      extend the portfolio of implants for treatment of periprosthetic fractures. The
      aim of this review article is to present the new procedures for osteosynthesis of
      periprosthetic fractures.

PMID- 23143033
TI  - Management of corneal bee sting: is surgical removal of a retained stinger always
      indicated?

PMID- 23143034
TI  - Visuospatial and verbal working memory load: effects on visuospatial vigilance.
AB  - In this study, we examined the impact of concurrent verbal and visuospatial
      working memory demands on performance of a visuospatial successive target
      detection task. Three hundred and four participants performed a visuospatial
      vigilance task while simultaneously performing either a spatial or verbal working
      memory task that either required a memory load during the vigil or did not
      require a memory load during the vigil. Perceptual sensitivity A' to vigilance
      target stimuli was reduced by concurrent memory load, both verbal and
      visuospatial. The decline in perceptual sensitivity to vigilance targets, the
      vigilance decrement, was steeper for a visuospatial memory task than a verbal
      memory task, regardless of concurrent memory load. Memory performance after
      vigilance detection trials was much lower for visuospatial than verbal items,
      even though memory performance before vigilance detection trials was higher for
      visuospatial than verbal items. Together, this indicates increased interference
      when a visuospatial vigilance task is paired with a visuospatial memory task,
      than when paired with a verbal memory task. Overall, the visuospatial and verbal
      working memory loads both impacted vigilance target detection, suggesting
      utilization of common executive resources. There may, however, be domain specific
      interference, and this may be exacerbated for two visuospatial tasks.

PMID- 23143035
TI  - Conclusions and data analysis: a 6-year study of Raman spectroscopy of solid
      tumors at a major pediatric institute.
AB  - PURPOSE: Create a Raman spectroscopic database with potential to diagnose cancer
      and investigate two different diagnostic methodologies. Raman spectroscopy
      measures the energy of photons scattered inelastically by molecules. These
      molecular signatures form the basis of identifying complex biomolecules and can
      be used to differentiate normal from neoplastic tissue. METHODS: 1,352 spectra
      from 55 specimens were collected from fresh or frozen normal brain, kidney and
      adrenal gland and their malignancies. Spectra were obtained utilizing a Renishaw
      Raman microscope (RM1000) at 785 nm excitation wavelength with an exposure time
      of 10 to 20 s/spectrum over three accumulations. Spectra were preprocessed and
      discriminant function analysis was used to classify spectra based on pathological
      gold standard. RESULTS: The results of leave 25 % out training/testing validation
      were as follows: 94.3 % accuracy for training and 91.5 % for testing adrenal,
      95.1 % accuracy for training and 88.9 % for testing group of brain, and 100 %
      accuracy for kidney training/testing groups when tissue origin was assumed. A
      generalized database not assuming tissue origin provided 88 % training and 85.5 %
      testing accuracy. CONCLUSION: A database can be made from Raman spectra to
      classify and grade normal from cancerous tissue. This database has the potential
      for real time diagnosis of fresh tissue and can potentially be applied to the
      operating room in vivo.

PMID- 23143036
TI  - Cadmium(Cd)-induced oxidative stress down-regulates the gene expression of DNA
      mismatch recognition proteins MutS homolog 2 (MSH2) and MSH6 in zebrafish (Danio
      rerio) embryos.
AB  - DNA mismatch repair (MMR) of simple base mismatches and small insertion-deletion
      loops in eukaryotes is initiated by the binding of the MutS homolog 2 (MSH2)-MSH6
      heterodimer to mismatched DNA. Cadmium (Cd) is a genotoxic heavy metal that has
      been recognized as a human carcinogen. Oxidant stress and inhibition of DNA
      repair have been proposed as major factors underlying Cd genotoxicity. Our
      previous studies indicated the ability of Cd to disturb the gene expression of
      MSH6 in zebrafish (Danio rerio) embryos. This study was undertaken to explore if
      Cd-induced oxidative stress down-regulated MSH gene activities. Following the
      exposure of zebrafish embryos at 1 h post fertilization (hpf) to sublethal
      concentrations of Cd at 3-5 MUM for 4 or 9 h, a parallel down-regulation of MSH2,
      MSH6 and Cu/Zn superoxide dismutase (Cu/Zn-SOD) gene expression was detected by
      real-time RT-PCR and the expression levels were 40-50% of control after a 9-h
      exposure. Cd exposure also induced oxidative stress, yet no inhibition of
      catalase gene activity was observed. Whole mount in situ hybridization revealed a
      wide distribution of msh6 mRNA in the head regions of 10 hpf embryos and
      pretreatment of embryos with antioxidants butylhydroxytoluene (BHT), d-mannitol
      or N-acetylcysteine (NAC) at 1-10 MUM restored Cd-suppressed msh6 expression.
      QPCR confirmed the protective effects of antioxidants on Cd-suppressed msh2/msh6
      mRNA production. Down-regulated MSH gene activities reaching about 50% of control
      were also induced in embryos exposed to paraquat, a reactive oxygen species (ROS)
      generating herbicide, or hydrogen peroxide at 200 MUM. Hence, Cd at sublethal
      levels down-regulates msh2/msh6 expression primarily via ROS as signaling
      molecules. The transcriptional activation of human msh6 is known to be fully
      dependent on the specificity factor 1 (Sp1). Cd failed to inhibit the DNA binding
      activity of zebrafish Sp1 unless at lethal concentrations based on band shift
      assay, therefore excluding the involvement of Sp1 inactivation in Cd-induced MSH
      gene inhibition in zebrafish embryos.

PMID- 23143037
TI  - Gene transcription and biomarker responses in the clam Ruditapes philippinarum
      after exposure to ibuprofen.
AB  - Pharmaceuticals are a class of emerging environmental contaminants that
      continuously enter aquatic environments. Presently, little information is
      available about the effects of these substances on non-target organisms, such as
      bivalves. We investigated the effects of ibuprofen (IBU) on the clam Ruditapes
      philippinarum. Clams were exposed for 1, 3, 5 and 7 days to 0, 100 and 1000
      MUgIBU/L, and established biomarker responses (haemolymph lysozyme, gill
      acetylcholinesterase and digestive gland superoxide dismutase activities) as well
      as digestive gland transcriptome were evaluated. A two-way ANOVA revealed
      significant effects of both "IBU concentration" and "exposure duration" on
      biomarker responses. Overall, the enzyme activities were generally lower in IBU
      exposed clams than in controls. Although limited knowledge of the mollusc
      transcriptome makes it difficult to interpret the effects of IBU on clams, the
      gene transcription analysis using DNA microarrays enabled the identification of
      the putative molecular mode of action of the IBU. The functional analysis of
      differentially transcribed genes suggests that IBU can interfere with various
      signalling pathways in clams, such as arachidonic acid metabolism, apoptosis,
      peroxisomal proliferator-activated receptors, and nuclear factor-kappa B. In
      addition, several genes involved in the metabolism of xenobiotics (e.g.,
      glutathione S-transferase, sulfotransferase, cytochrome P450) were also found to
      be significantly affected by IBU exposure. In summary, the integrated approach of
      gene transcription analysis and biomarker responses facilitated the elucidation
      of the putative mechanisms of action of IBU in non-target species.

PMID- 23143038
TI  - Effects of exposure to 17alpha-ethynylestradiol during larval development on
      growth, sexual differentiation, and abundances of transcripts in the liver of the
      wood frog (Lithobates sylvaticus).
AB  - Populations of amphibians are in decline in certain locations around the world,
      and the possible contribution of environmental contaminants, including estrogenic
      compounds, to these declines is of potential concern. In the current study,
      responses of the wood frog (Lithobates sylvaticus) to exposure to 17alpha
      ethynylestradiol (EE2), the synthetic estrogen used in oral contraceptives,
      during the larval period were characterized. Exposure of L. sylvaticus to 1.08,
      9.55, or 80.9 MUg EE2/L had no effects on survival, growth, or metamorphic
      endpoints monitored in the current study. However, there were significant effects
      of exposure to EE2 on phenotypic sex ratios. In general, lesser proportions of L.
      sylvaticus developed as phenotypic males and greater proportions developed as
      phenotypic females or with mixed sex phenotypes at all concentrations of EE2
      tested. Utilizing the data collected in the current study, the EC(50) for
      complete feminization of L. sylvaticus was determined to be 7.7 MUg EE2/L, and
      the EC(50) for partial feminization was determined to be 2.3 MUg EE2/L. In
      addition, after chronic exposure, abundances of transcripts of vitellogenin A2,
      high density lipoprotein binding protein, and 7-dehydrocholesterol reductase were
      1.8-280-fold greater in livers from L. sylvaticus exposed to EE2 compared to
      controls. Overall, there were significant effects of exposure to all
      concentrations of EE2 tested, the least of which was within about 2-fold of
      estrogen equivalent concentrations previously measured in the environment.

PMID- 23143039
TI  - Temperature dependence of long-term cadmium toxicity in the zebrafish is not
      explained by liver oxidative stress: evidence from transcript expression to
      physiology.
AB  - Standard ecotoxicity tests are performed at species' specific standard
      temperatures, but temperature is known to affect chemical toxicity. A temperature
      increase has been shown to increase cadmium toxicity in several aquatic species
      but information in fish is scarce. Based on literature we hypothesize that with
      increasing temperature, cadmium accumulation and oxidative stress increase,
      resulting in increased toxicity. In this study zebrafish acclimated to 12, 18, 26
      (standard temperature) or 34 degrees C for one month, were exposed to 5 MUM
      cadmium for 4 or 28 days at the respective acclimation temperature. Cadmium
      toxicity (mortality) increased with increasing temperature. PCA showed that the
      high mortality at 34 degrees C was closely correlated to an increasing tissue
      cadmium accumulation with increasing temperature, but not to liver oxidative
      damage under the form of protein carbonyl content or lipid peroxidation (measured
      as malondialdehyde levels) or liver antioxidative potential. Instead, acclimation
      to 12 degrees C induced the highest oxidative damage to liver proteins and
      lipids, and transcript levels of glucose-6P-dehydrogenase, 6P-gluconate
      dehydrogenase and glutathione peroxidase were particularly good markers of cold
      induced oxidative stress. At this low temperature there was no interaction with
      cadmium exposure and there was no sign of cadmium sensitivity. Contrastingly, the
      combined effect of high temperature and cadmium exposure on mortality proved
      synergistic. Therefore we conclude that interactions between temperature and
      cadmium toxicity increased with increasing temperature and that this probably
      played part in increasing cadmium sensitivity. Increased cadmium
      compartmentalization and protein carbonyl content in liver of zebrafish
      acclimated to the standard temperature of 26 degrees C probably played part in
      increased sensitivity towards the same cadmium body burden compared to lower
      temperatures. On the one hand we recognize and this study even confirms the
      importance of applying standard temperatures in standard ecotoxicity tests to
      ensure inter-study comparability. On the other hand temperatures in the field may
      deviate from standard temperatures and accounting for deviating temperatures,
      which can alter chemical sensitivity, in regulation can improve environmental
      protection.

PMID- 23143040
TI  - Differential responses in ammonia excretion, sodium fluxes and gill permeability
      explain different sensitivities to acute high environmental ammonia in three
      freshwater teleosts.
AB  - We examined the acute physiological responses to high environmental ammonia
      (HEA), particularly the linkages between branchial ammonia fluxes and
      unidirectional Na(+) fluxes, as well as urea excretion, cortisol, and indicators
      of gill permeability in three freshwater teleosts differing in their
      sensitivities to ammonia; the highly sensitive salmonid Oncorhynchus mykiss
      (rainbow trout), the less sensitive cyprinid Cyprinus carpio (common carp) and
      the highly resistant cyprinid Carassius auratus (goldfish). Fish were acutely
      exposed to two sub-lethal ammonia concentrations (as NH(4)HCO(3)) at pH 7.9: 1 mM
      for a period of 12 h, identical for all species, and 5 mM for the cyprinids and
      1.4 mM for the trout for 3 h. Elevation of plasma cortisol at both levels of HEA
      was apparent in all species. At 1 mM, ammonia excretion (J(amm)) was inhibited to
      a greater extent in trout than cyprinids and concurrently a significantly higher
      plasma ammonia level was evident in trout. However J(amm) was reversed in all
      species at 5 or 1.4 mM. Goldfish showed a significant increase in urea excretion
      rate (J(urea)) during HEA exposure. In carp and trout, neither level of HEA
      elevated J(urea) but urea production was increased as evidenced by a considerable
      elevation of plasma urea. At 1mM HEA, Na(+) imbalance became progressively more
      severe in trout and carp due to a stimulation of unidirectional Na(+) efflux
      (J(out)(Na)) without a concomitant increase in unidirectional Na(+) influx
      (J(in)(Na)). Additionally, a transient reduction of J(in)(Na) was evident in
      trout. Goldfish showed an opposite trend for J(out)(Na) with reduced efflux rates
      and a positive Na(+) balance during the first few hours of HEA. However, after 12
      h of exposure, both J(in)(Na) and J(out)(Na) were also increased in both carp and
      goldfish, whereas only J(out)(Na) was increased in trout, leading to a net Na(+)
      loss. Na(+) homeostasis was entirely disrupted in all three species when
      subjected to the 5 or 1.4 mM ammonia for 3 h: J(in)(Na) was significantly
      inhibited while considerable activation of J(out)(Na) was observed. Diffusive
      water efflux rates and net K(+) loss rates across the gills were enhanced during
      HEA only in trout, indicating an increment in gill transcellular permeability.
      Transepithelial potential was increased in all the species during ammonia
      exposure, but to the least extent in goldfish. Overall, for several different
      physiological systems, trout were most disturbed, and goldfish were least
      disturbed by HEA, helping to explain the differential ammonia tolerance of the
      three species.

PMID- 23143041
TI  - MRSA screening by the Xpert MRSA PCR assay: pooling samples of the nose, throat,
      and groin increases the sensitivity of detection without increasing the
      laboratory costs.
AB  - The performance of the Xpert MRSA polymerase chain reaction (PCR) assay on pooled
      nose, groin, and throat swabs (three nylon flocked eSwabs into one tube) was
      compared to culture by analyzing 5,546 samples. The sensitivity [0.78, 95 %
      confidence interval (CI) 0.73-0.82] and specificity (0.99, 95 % CI 0.98-0.99)
      were similar to the results from published studies on separated nose or other
      specimens. Thus, the performance of the Xpert MRSA assay was not affected by
      pooling the three specimens into one assay, allowing a higher detection rate
      without increasing laboratory costs, as compared to nose samples alone.

PMID- 23143042
TI  - The C-terminal domain of the 2b protein of Cucumber mosaic virus is stabilized by
      divalent metal ion coordination.
AB  - The main function of the 2b protein of Cucumber mosaic virus (CMV) is binding
      permanently the double stranded siRNA molecules in the suppression process of
      post-transcriptional gene silencing (PTGS). The crystal structure of the
      homologue Tomato aspermy virus (TAV) 2b protein is known, but without the C
      terminal domain. The biologically active form is a tetramer: four 2b protein
      molecules and two siRNA duplexes. Regarding the complete 2b protein structure, we
      performed a molecular dynamics (MD) simulation of the whole siRNA-2b
      ribonucleoprotein complex. Unfortunately, the C-terminal domain is proved to be
      partially unstructured. Multiple sequence alignment showed a well conserved motif
      between residues 94 and 105. The negatively charged residues of the C-terminal
      domain are supposed to take part in coordination of a divalent metal ion and
      stabilize the three-dimensional structure of the C-terminal domain. MD
      simulations were performed on the detached C-terminal domains (aa 65-110). 0.15 M
      MgC2, CaCl2, FeCl2 and ZnCl2 salt concentrations were used in the screening
      simulations. Among the tested divalent metal ions Mg2+ proved to be very
      successful because Asp95, Asp96 and Asp98 forms a quasi-permanent Mg2+ binding
      site. However the control computations have resulted in any (at least) divalent
      metal ion remains in the binding site after replacement of the bound Mg2+ ion. A
      quadruple mutation (Rs2DDTD/95-98/AAAA) was introduced into the position of the
      putative divalent metal ion binding site to analyze the biological relevance of
      molecular modeling derived hypothesis. The plant inoculation experiments proved
      that the movement of the mutant virus is slower and the symptoms are milder
      comparing to the wild type virus. These results demonstrate that the quadruple
      mutation weakens the stability of the 2b protein tetramer-siRNA ribonucleoprotein
      complex.

PMID- 23143043
TI  - DNA-based delivery vehicles: pH-controlled disassembly and cargo release.
AB  - Non-Watson-Crick base pairing provides an in situ approach for actuation of DNA
      nanostructures through responses to solution conditions. Here we demonstrate this
      concept by using physiologically-relevant changes in pH to regulate DNA pyramid
      assembly/disassembly and to control the release of protein cargo.

PMID- 23143044
TI  - The effect of intravenous glucose solutions on neonatal blood glucose levels
      after cesarean delivery.
AB  - PURPOSE: Intravenous solutions are often administered to the mother on the day of
      a cesarean delivery to minimize the effect of preoperative fasting or to
      stabilize the hemodynamics. Different intravenous solutions contain varying
      amounts of glucose, and rapid administration may lead to hypoglycemia in the
      neonate. We conducted a study to compare blood glucose levels of the mother and
      the fetus/neonate after they were rapidly given a Ringer's solution containing 0,
      1, or 5 % glucose. The effect of the glucose load that these intravenous
      solutions impose during cesarean delivery has not been fully reported. Therefore,
      we compared the effect of 0 % (Group I, n = 15), 1 % (Group II, n = 15), and 5 %
      (Group III, n = 15) glucose acetated Ringer's solutions on maternal and umbilical
      blood glucose levels to determine the optimal glucose concentration. METHODS:
      Once the patients were in the operating room, the intravenous solutions were
      administered before delivery. The primary endpoint was changes in umbilical blood
      glucose levels and minimum neonatal blood glucose levels, and the secondary
      endpoint was the proportion of neonates who received a glucose infusion. RESULTS:
      Maternal blood glucose levels before and after intravenous infusion were 79.2 +/-
      12.2 and 74.6 +/- 4.6 in Group I, 81.2 +/- 12.9 and 103.3 +/- 11.2 in Group II (P
      < 0.001), and 82.3 +/- 8.7 and 252.5 +/- 41.8 in Group III (P < 0.001). Umbilical
      blood glucose levels were 53.9 +/- 10.2 in Group I, 80.8 +/- 13.7 in Group II,
      and 181.8 +/- 22.2 in Group III (P < 0.01: Group I vs. Group II and P < 0.01:
      Group II vs. Group III) (P < 0.001: Group I vs. Group III). Minimum neonatal
      blood glucose levels measured up to 8 h after birth were 35.7 +/- 9.6 in Group I,
      49.8 +/- 10.8 in Group II, and 29.2 +/- 7.5 in Group III. Neonatal hypoglycemia
      requiring glucose before the first milk feeding occurred in 6 neonates whose
      mothers were in Group I, 3 in Group II, and 9 in Group III, indicating a trend
      towards less neonatal hypoglycemia in Group II. CONCLUSIONS: The use of 1 %
      glucose acetated Ringer's solution did not induce hyperglycemia in the mother and
      it was able to maintain appropriate blood glucose levels in the fetus.

PMID- 23143045
TI  - Potassium iodide catalyzed simultaneous C3-formylation and N-aminomethylation of
      indoles with 4-substituted-N,N-dimethylanilines.
AB  - A one-pot dual functionalization of indoles has been developed. The simultaneous
      C3-formylation and N-aminomethylation of indoles can be achieved using readily
      available potassium iodide as a catalyst and tert-butyl peroxybenzoate as a co
      oxidant.

PMID- 23143046
TI  - Abdominal aortic aneurysm with bony erosion mimicking recurrent non-Hodgkin
      lymphoma on FDG PET/CT.
AB  - An 80-year-old man with a history of non-Hodgkin lymphoma in complete remission
      after chemotherapy in 2009 presented with lumbar pain. MRI demonstrated anterior
      L4 bony erosions. FDG PET/CT revealed the large retroperitoneal mass with central
      photopenia and a mildly hypermetabolic rim. Ultrasound revealed a dilated aorta
      with atherosclerotic plaque and eccentric mural thrombus. A newly developed mass
      like lesion in a patient with history of lymphoma could be mistaken for lymphoma
      recurrence on FDG PET/CT.

PMID- 23143047
TI  - Usefulness of (18)F-FDG PET/CT in disease extent and treatment response
      assessment in a patient with syphilitic aortitis.
AB  - A 40-year-old man was admitted to our hospital for surgical treatment of aortic
      insufficiency and coronary ostial stenosis. Histopathology and serological tests
      revealed a syphilitic aortitis. F-FDG PET/CT was performed to assess the extent
      of aortitis, showing increased radiopharmaceutical uptake along the ascending
      aortic wall. A repeated FDG PET/CT after antibiotic therapy showed a markedly
      reduced uptake in the aortic wall, suggesting resolution of the infection
      according to clinical and serological data. This case highlights the usefulness
      of FDG PET/CT for the assessment of disease extent and treatment response in
      patients with syphilitic aortitis.

PMID- 23143048
TI  - Adenocarcinoma arising in Meckel's diverticulum on 18F-FDG PET/CT.
AB  - A 19-year-old girl presented with lower abdominal pain. Pelvic ultrasound showed
      a large cystic mass in the pelvic cavity, and CA19-9 was markedly elevated. On
      further evaluation, (18)F-FDG PET/CT showed heterogeneous, localized FDG uptake
      with a central photon defect in the pelvic cavity, and most intense FDG uptake
      was noted in the anterior portion of lesion adjacent to the ileum. Corresponding
      enhanced CT showed a cystic mass abutting the ileum with wall thickening.
      Laparoscopic resection was done and the histologic result was adenocarcinoma
      arising in Meckel's diverticulum.

PMID- 23143049
TI  - The value of 18F-FDG PET/CT after autologous stem cell transplantation (ASCT) in
      patients affected by multiple myeloma (MM): experience with 77 patients.
AB  - AIM: The objective of this study was to analyze the prognostic value of (18)F-FDG
      PET/CT after therapy in patients with multiple myeloma (MM). PATIENTS AND
      METHODS: One hundred seven patients prospectively recruited with MM had FDG
      PET/CT at staging 3 months after therapy (autologous stem cell transplantation)
      and every 6 to 12 months during the follow-up (mean 41 months). Patients were
      divided into group 1 (relapsed) and group 2 (nonrelapsed). In group 1, PET
      results and SUV(max) were compared to the time to relapse (TTR). In group 2, the
      presence of PET finding changes during follow-up was analyzed to identify typical
      patterns of disease behavior (ie, late responders or stabilized disease).
      Patients with a negative PET at staging were excluded from further evaluation.
      RESULTS: Forty-seven out of 107 (44%) patients relapsed: 10 were excluded because
      of a negative PET at staging. In group 1, 22 patients had a negative posttherapy
      PET (59%, mean TTR = 27.6 months) and 15 had a positive posttherapy PET (41%,
      mean TTR = 18 months). There was a significant difference between the TTR of the
      two subgroups (t test P = 0.05). In patients with a positive posttherapy PET, the
      SUV(max) was inversely correlated to the TTR (correlation coefficient = -0.7; P <
      0.01).Sixty out of 107 (56%) patients did not relapse. Twenty patients were
      excluded because of a negative PET at staging. In group 2, 27 patients had a
      negative posttherapy PET (68%) and 13 had a positive posttherapy PET (32%). None
      of nonrelapsed patients showed a progressive increase in SUV(max) during the
      follow-up. There was no significant difference between relapsed and nonrelapsed
      patients in terms of SUV(max) at posttherapy PET/CT (t test P = 0.7). CONCLUSION:
      In our series of MM patients, a negative posttherapy PET was predictive for
      nonrelapse or a long disease-free survival. In contrast, a persistent
      significantly increased SUV(max) after therapy was correlated to a short TTR.

PMID- 23143050
TI  - (18)F-fluoride PET/CT in avascular necrosis of the femoral head.
AB  - Avascular necrosis (AVN) of the femoral head is a devastating disease in young
      adults. Magnetic resonance imaging is considered the most sensitive and specific
      technique in the diagnosis of this condition. The authors present an interesting
      image of bilateral AVN of the femoral heads diagnosed on F-fluoride positron
      emission tomography/computed tomography.

PMID- 23143051
TI  - Incidental detection of a vesicocolonic fistula on renal scintigraphy with
      SPECT/CT.
AB  - Urinary-enteric fistula is a rare cause of recurrent urinary tract infection
      (UTI). Therefore, delayed/incidental diagnosis is the rule. The authors present
      an image of a vesicocolonic fistula incidentally detected during SPECT/CT renal
      scintigraphy with 99mTc-DTPA in a female patient with recurrent UTI. The
      diagnosis was subsequently confirmed by cystoscopy and surgery.

PMID- 23143052
TI  - Intramural metastases of rectum from carcinosarcoma (malignant mullerian mixed
      tumor) of uterine cervix.
AB  - A 25-year-old woman had carcinosarcoma of uterine cervix after definitive
      treatment. One year later, local recurrent disease was found in the right
      posterior pelvis on FDG PET/CT. FDG PET/CT also disclosed an incidental
      intramural hypermetabolic lesion in the rectum, which seemed separate from the
      right pelvic lesion on contrast-enhanced CT. The rectal lesion was confirmed as
      metastatic carcinosarcoma from uterine cervix after endoscopic biopsy.

PMID- 23143053
TI  - Severe traumatic brain injury and controlled hemorrhage in rats:  quest for the
      optimal mean arterial blood pressure after whole fresh donor blood resuscitation.
AB  - Treatment of combined traumatic brain injury and hypovolemic shock poses a
      particular challenge due to the possible conflicting consequences. While
      restoring diminished volume is the treatment goal for hypovolemia, maintaining
      and adequate cerebral perfusion pressure and avoidance of secondary damage remain
      a treatment goal for the injured brain. Various treatment modalities have been
      proposed, but the optimal resuscitation fluid and goals have not yet been clearly
      defined. In this study, we investigate the physiological and neurological
      outcomes in a rat model of combined traumatic brain injury and hypovolemic shock,
      submitted to treatment with varying amounts of fresh blood. Forty-eight male
      Lewis rats were divided into control and treatment groups. Traumatic brain injury
      was inflicted by a free-falling rod on the exposed cranium. Hypovolemia was
      induced by controlled hemorrhage of 30% blood volume. Treatment groups were
      treated by fresh whole blood with varying volumes, reaching resuscitation goals
      of a mean arterial blood pressure (MAP) of 80, 100, and 120 mmHg at 15 min. Mean
      arterial blood pressure was assessed at 60 min and neurological outcomes and
      mortality in the subsequent 48 h. At 60 min, MAP was highest for the group
      resuscitated most aggressively. Neurological outcomes and mortality inversely
      correlated with the aggressiveness of resuscitation. In this study, we find that
      mild resuscitation with goals of restoring MAP to 80 mmHg (which is lower than
      baseline) provided best results when considering hemodynamic stability, survival,
      and neurological outcomes. An aggressive resuscitation may be detrimental,
      inducing processes that eventually cause a significant decrease in survival.

PMID- 23143054
TI  - Ketoprofen impairs immunosuppression induced by severe sepsis and reveals an
      important role for prostaglandin E2.
AB  - The mechanism of immunosuppression induced by severe sepsis is not fully
      understood. The production of prostaglandin E2 (PGE2) during sepsis is well
      known, but its role in long-term consequences of sepsis has not been explored.
      The current study evaluates the role of PGE2 in the development of
      immunosuppression secondary to sepsis and its potential as therapeutic target.
      Cecal ligation and puncture was used as an experimental model for sepsis
      induction in Balb/c and C57BL/6 mice. Immunosuppression was evaluated by the
      response to secondary infection with Aspergillus fumigatus in sepsis survivors.
      The role of prostanoids was evaluated in vivo and in vitro by treatment with the
      cyclooxygenase inhibitor ketoprofen. Balb/c mice were more susceptible than
      C57BL/6 to severe sepsis and to secondary infection, with a greater mortality
      rate. Prostaglandin E2 concentrations found in bronchoalveolar lavage in sham and
      cecal ligation and puncture group after fungal challenge were much higher in
      Balb/c than in C57BL/6 mice. Ketoprofen treatment improved survival of septic
      Balb/c mice subjected to secondary infection, while also enhancing macrophage
      phagocytosis and neutrophil recruitment to the lungs. We identified a pivotal
      role for PGE2 acting on EP4 receptors in modulating cytokine production
      differentially by sham and septic macrophages. Furthermore, sepsis also altered
      key enzymes in PGE2 synthesis and degradation. Our results indicate the
      involvement of PGE2 in severe sepsis-induced immunosuppression. Inhibition of
      PGE2 production represents an attractive target to improve innate immune response
      against secondary infection in the immunocompromised host.

PMID- 23143055
TI  - A new severity predicting index for hemorrhagic shock using lactate concentration
      and peripheral perfusion in a rat model.
AB  - Forty percent of trauma deaths are due to hemorrhage, with 33% to 56% occurring
      in the prehospital environment. This study proposes a new index (NI) based on the
      ratio of serum lactate concentration (LC) to peripheral perfusion (PP) as an
      indicator of hemorrhage-induced mortality during the prehospital stage. Thirty
      six anesthetized rats were randomized into three groups according to volume of
      controlled blood loss. We measured heart rate (HR), systolic and diastolic blood
      pressures (SBP and DBP), mean arterial pressure (MAP), pulse pressure (PPR),
      respiration rate (RR), temperature (TEMP), LC, PP, shock index (SI = HR/SBP), and
      proposed the new hemorrhage-induced mortality index (NI = LC/PP). Peripheral
      perfusion, defined as peripheral tissue perfusion and skin microcirculation, was
      continuously monitored by laser Doppler flowmetry. All parameters were analyzed
      for changes between prehemorrhage and posthemorrhage to investigate the effects
      of hemorrhage on mortality. Areas under a receiver operating characteristic curve
      (AUCs) in descending order for NI, SI, PP, SBP, MAP, PPR, DBP, TEMP, LC, RR, and
      HR were 0.975, 0.941, 0.922, 0.919, 0.903, 0.884, 0.847, 0.816, 0.783, 0.744, and
      0.672, respectively. The correlation coefficients with mortality for NI, SI, PP,
      SBP, MAP, PPR, DBP, TEMP, LC, RR, and HR were -0.818, -0.759, 0.726, 0.721,
      0.694, 0.662, 0.597, 0.544, -0.487, 0.420, and -0.296, respectively, with the
      same order as the AUC. NI was shown to be an optimal independent mortality
      predictor on multivariable logistic regression analysis. In conclusion, the newly
      proposed hemorrhage-induced mortality index, based on blood lactate/PP ratio, was
      a better marker for predicting mortality in rats undergoing acute hemorrhage in
      comparison to the other parameters evaluated in this study.

PMID- 23143056
TI  - Attenuation of mitochondrial unfolded protein response is associated with hepatic
      dysfunction in septic rats.
AB  - This study was conducted to reveal if the mitochondrial unfolded protein response
      (mtUPR), a conserved mitochondrial-nuclear communication mechanism, plays a
      critical role in the protein quality control system to cope with damaged protein
      during sepsis. Sepsis was induced by cecal ligation and puncture (CLP) in Sprague
      Dawley rats. The efficiency of mtUPR was evaluated by measuring the
      transcriptional factors (CCAAT/enhancer-binder protein homologous protein [CHOP]
      and CCAAT/enhancer-binder protein-beta) and chaperones (heat shock protein 60
      [Hsp60] and Hsp10) expression in response to hepatic mitochondrial oxidized
      proteins (carbonylated proteins, car-proteins) and multi-ubiquitinated proteins
      (ub-proteins). The results showed that car-proteins and ub-proteins were
      significantly increased at 9 and 18 h after CLP. In addition, serum glutamic
      oxaloacetic transaminase and glutamic-pyruvic transaminase were significantly
      positively correlated with mitochondrial car-proteins and ub-proteins and
      negatively with intramitochondrial adenosine triphosphate. The expression of
      mitochondrial Hsp60 and Hsp10 decreased notably during the progression of sepsis,
      implying that failure of mtUPR occurred in the late septic liver. Interestingly,
      we evaluated the ratio of mitochondrial Hsp60/Hsp10 to the ub-proteins and found
      that both ratios were statistically lowered at the time points of 9 and 18 h in
      comparison with 3 and 6 h after CLP. These ratios were also significantly
      negatively correlated with glutamic-oxaloacetic transaminase and glutamic-pyruvic
      transaminase levels, suggesting that the ratios could act as an index of mtUPR
      failure and be a useful tool in estimating the ability of mitochondrial-nuclear
      communication in sepsis. In conclusion, the results indicated that mtUPR failure
      occurred during sepsis, and that the index of mtUPR may be a valuable measurement
      in assessing the severity of organ dysfunction in the clinical setting.

PMID- 23143057
TI  - The acute immunological response to blood transfusion is influenced by
      polymicrobial sepsis.
AB  - Blood transfusion is a well-established risk factor for adverse outcomes during
      sepsis. The specific mechanisms responsible for this effect remain elusive, and
      few studies have investigated this phenomenon in a model that reflects not only
      the clinical circumstances in which blood is transfused, but also how packed red
      blood cells (PRBCs) are created and stored. Using a cecal ligation and puncture
      model of polymicrobial sepsis as well as creating murine allogeneic and stored
      PRBCs in a manner that replicates the clinical process, we have demonstrated that
      transfusion of PRBCs induces numerous effects on leukocyte subpopulations. In
      polymicrobial sepsis, these responses are profoundly dissimilar to the
      proinflammatory effects of PRBC transfusion observed in the healthy mouse.
      Transfused septic mice, as opposed to mice receiving crystalloid resuscitation,
      had a significant loss of blood, spleen, and bone marrow lymphocytes, especially
      those with an activated phenotype. Myeloid cells behaved similarly, although they
      were able to produce more reactive oxygen species. Overall, transfusion in the
      septic mouse may contribute to the persistent immune dysfunction known to be
      associated with this process, rather than simply promote proinflammatory or anti
      inflammatory effects on the host. Thus, it is possible that blood transfusion
      contributes to the multiple known effects of sepsis on leukocyte populations that
      have been shown to result in increased morbidity and mortality.

PMID- 23143058
TI  - Hydrogen sulfide differentially affects the hepatic vasculature in response to
      phenylephrine and endothelin 1 during endotoxemia.
AB  - Despite being protective in many disease states, hydrogen sulfide (H(2)S)
      contributes to organ injury in sepsis. Like the other gasotransmitters, nitric
      oxide and carbon monoxide, H(2)S is a modulator of the microcirculation. Because
      microcirculatory dysfunction is a main cause of organ injury during sepsis, the
      present study was designed to test the effect of H(2)S on microvascular
      dysfunction in isolated perfused livers. In most microcirculatory beds, endotoxin
      activates the endothelium, resulting in hyporesponsiveness to catecholamines and
      a derangement in blood flow distribution. We demonstrate that H(2)S treatment
      attenuates the increase in portal pressure during infusion of the alpha1
      adrenergic agonist, phenylephrine (PE) (P < 0.01). Hydrogen sulfide almost
      completely negated the increase in portal pressure in livers isolated from
      endotoxemic rats. Treatment with an inhibitor of endogenous H(2)S, DL
      propargylglycine (PAG), reversed lipopolysaccharide-induced hyporesponsiveness to
      PE. Because hepatic microcirculatory dysfunction is associated with excessive
      sinusoidal vasoconstriction and not dilation, we investigated whether H(2)S
      affects endothelin 1 (ET-1)-induced vasoconstriction in isolated livers. Contrary
      to PE treatment, H(2)S did not affect the increase in portal pressure during
      infusion of ET-1, nor did it attenuate the hypersensitization of the liver to ET
      1 during endotoxemia. Hepatic resistance in control rats was increased by PAG
      treatment during ET-1 infusion, but this increase was not exacerbated during
      endotoxemia. We monitored hepatic O(2) consumption to assess the effect of
      vascular changes on oxygen consumption following ET-1 treatment. Low-dose ET-1
      infusion caused an increase in hepatic O(2)consumption, whereas low-dose ET-1
      infusion decreased O(2) consumption in endotoxemic livers. Interestingly, whereas
      we observed no effect of PAG on the vascular response to ET-1 infusion during
      endotoxemia, PAG treatment did maintain O(2), suggesting a more complex effect of
      H(2)S inhibition. In summary, the discrepancies between the hepatic response to
      PE and ET-1 suggest that H(2)S differentially contributes to microcirculatory
      dysfunction in the systemic and hepatic microcirculations. We propose that this
      is due to H(2)S exerting a differential vasoactive function on presinusoidal and
      sinusoidal sites within the liver. Moreover, our findings suggest that H(2)S may
      contribute to the progression of sepsis by contributing to microvascular failure.

PMID- 23143059
TI  - Effect of high advanced glycation end-product diet on pulmonary inflammatory
      response and pulmonary function following gastric aspiration.
AB  - It is not clear why some patients with aspiration advance to acute lung injury or
      acute respiratory distress syndrome, whereas others do not. The Western diet is
      high in advanced glycation end-products (AGEs), which have been found to be
      proinflammatory. We hypothesize that dietary AGEs exaggerate the pulmonary
      inflammatory response following gastric aspiration. CD-1 mice were randomized to
      receive either a low-AGE (LAGE) or a high-AGE (HAGE) diet for 4 weeks. Five hours
      after intratracheal instillation of acidified small gastric particles, pulmonary
      function was determined. Polymorphonuclear neutrophil counts, albumin,
      cytokine/chemokine, and tumor necrosis factor soluble receptor II concentrations
      in the bronchoalveolar lavage and lung myeloperoxidase activity were measured.
      Compared with LAGE-fed animals, those fed a HAGE diet had increased lung tissue
      resistance (P = 0.017), bronchoalveolar lavage albumin concentration (P < 0.05),
      pulmonary polymorphonuclear neutrophil counts (P = 0.0045), and lung
      myeloperoxidase activity (P = 0.002) following aspiration. In addition, the
      plasma levels of tumor necrosis factor soluble receptor II were significantly
      elevated (P < 0.05), whereas paradoxically levels of keratinocyte chemoattractant
      and monocyte chemoattractant protein 1 were decreased in mice with HAGE diet. In
      conclusion, a diet high in AGEs exacerbates acute lung injury following gastric
      aspiration as evidenced by increases in neutrophil infiltration, airway albumin
      leakage, and decreased pulmonary compliance. This is the first evidence
      implicating exacerbation of acute inflammatory lung injury by dietary AGEs.
      Targeting AGEs in the circulatory system may offer a therapeutic strategy for
      limiting lung injury following gastric aspiration.

PMID- 23143060
TI  - Circulating monocytes are not the major source of plasma cytokines in patients
      with sepsis.
AB  - In sepsis, large quantities of inflammatory cytokines are released into the
      bloodstream. The cellular source of these cytokines is unclear, and we have here
      investigated to what extent circulating cells in blood contributed to this
      production. We used the enzyme-linked immunospot technique to study the
      spontaneous as well as the lipopolysaccharide (LPS)-induced secretion of the
      proinflammatory cytokines interleukin 6 (IL-6), tumor necrosis factor alpha (TNF
      alpha), granulocyte-macrophage colony-stimulating factor, IL-1beta, IL-12p40, and
      the anti-inflammatory cytokine IL-10 from whole-blood cells. The study comprised
      32 septic patients (24 with septic shock) and 30 healthy controls. Despite
      significantly increased plasma cytokine levels in the septic patients, the number
      of spontaneous cytokine-secreting cells was small or nonexistent and did not
      differ between the two groups. Lipopolysaccharide stimulation of cells from the
      same samples triggered substantially increased numbers of cytokine-producing
      cells in both patients and controls. However, although the numbers of IL-6- and
      tumor necrosis factor alpha-secreting monocytes were very similar in both groups,
      significantly fewer IL-1beta-, IL-10-, IL-12p40-, and granulocyte-macrophage
      colony-stimulating factor-secreting monocytes were seen in samples from septic
      patients as compared with healthy controls. The reduced number of cytokine
      secreting cells in response to LPS stimulation correlated with disease severity,
      as expressed by Sequential Organ Failure Assessment score and the stage of
      sepsis. In summary, circulating leukocytes did not appear to be responsible for
      the increased plasma levels of cytokines observed in sepsis. A selective sepsis
      induced downregulation of cytokine secretion in response to LPS underscores the
      complexity of cytokine regulation in sepsis.

PMID- 23143061
TI  - Follistatin does not influence the course of Escherichia coli K1 sepsis in a
      mouse model.
AB  - Follistatin (FS) is the binding protein of activin A and inhibits its actions.
      The activin/FS system participates in the fine tuning of the immune response, and
      concentrations of activin A and FS are elevated in serum of patients with sepsis.
      Intraperitoneal injection of FS markedly reduced mortality after
      lipopolysaccharide-induced inflammation in a mouse model. Here, we investigated
      whether FS also influences the disease course in a mouse model of sepsis induced
      by intraperitoneal injection of Escherichia coli K1, a gram-negative bacterium
      frequently causing septic bacterial infections. Intraperitoneal injection of 10
      MUg/mL FS 30 min before infection did not influence survival, weight, motor
      performance, or bacterial titers of the infected mice. Thus, we could not confirm
      the protective effect of FS observed during lipopolysaccharide-induced
      inflammation in our mouse model of E. coli sepsis. Although it is a promising
      therapeutic tool in chronic or acute inflammatory conditions not caused by
      virulent pathogens, FS does not seem to increase the resistance to bacterial
      infections.

PMID- 23143062
TI  - MicroRNA-27a regulates cardiomyocytic apoptosis during cardioplegia-induced
      cardiac arrest by targeting interleukin 10-related pathways.
AB  - In this study, experiments were designed to determine whether microRNAs (miRNAs)
      play a role in the regulation or modulation of cardiomyocytic reactions under
      cardioplegia-induced cardiac arrest during cardiopulmonary bypass. MicroRNAs play
      powerful and unexpected roles in numerous cardiovascular diseases. MicroRNA-based
      therapeutics may provide a unique opportunity to translate this knowledge into
      the clinical setting. Sprague-Dawley rats (10 per group) were randomly divided
      into three groups: control, perfusion, and arrest groups. In the perfusion group,
      isolated hearts were perfused with oxygenated physiologic buffered solution for 3
      h using a Langendorff apparatus. In the arrest group, cold crystalloid
      cardioplegia solution was used to induce and maintain cardiac arrest for 1 h;
      hearts were reperfused for 2 h with warm oxygenated phosphate-buffered saline
      solution. Cardiac miRNAs and protein expression patterns were detected using
      miRNA arrays and two-dimensional fluorescence difference gel electrophoresis
      followed by matrix-assisted laser desorption/ionization-time of flight mass
      spectrometry. Of 103 different miRNAs and 222 different proteins expressed in the
      three groups, miRNA-27a was the one considered to be related to the regulation of
      cardiomyocyte apoptosis by targeting the interleukin 10 pathway. Transfection of
      H9c2 cardiomyocytes with pre-miRNA-27a, which significantly decreased the mRNA
      and protein levels of interleukin 10 and increased expression of nuclear factor
      kappaB and its downstream cytokines during hypoxia/reperfusion injury, could
      activate caspase 3 and apoptosis. Our study demonstrated the altered expression
      of miRNAs in cardiomyocytes during cardioplegia-induced cardiac arrest. The
      involvement of miRNAs in cardiomyocytic apoptosis adds another level of
      complexity to gene regulation, which could open up novel avenues for cardiac
      protection strategies during cardiac surgery.

PMID- 23143064
TI  - Central venous oxygen saturation under non-protocolized resuscitation is not
      related to survival in severe sepsis or septic shock.
AB  - Protocolized hemodynamic resuscitation in severe sepsis or septic shock is not
      universally applied in all emergency departments and general hospital wards
      around the world. It is unknown whether ScvO2 levels are associated with the
      clinical outcome of severe sepsis or septic shock under nonprotocolized
      resuscitation. In this prospective study, we enrolled 124 noncirrhotic patients
      who were admitted to intensive care units for severe sepsis or septic shock. The
      average Acute Physiology and Chronic Health Evaluation II score was 25.3 (SD,
      7.6). According to ScvO2 levels after initial resuscitation before intensive care
      unit admission, patients were divided into high (ScvO2 >= 70%, n = 63) and low
      (ScvO2 < 70%, n = 61) ScvO2 groups. Compared with high ScvO2 groups, low ScvO2
      groups showed no significant differences in 28-day mortality (25.4% vs. 24.6%; P
      = 0.943) or hospital mortality (30.2% vs. 31.1%; P = 0.794). Multivariate
      logistic regression models showed that low mean arterial pressure (hazard ratio,
      0.967; 95% confidence interval, 0.940-0.994; P = 0.019) and high central venous
      pressure (hazard ratio, 1.150; 95% confidence interval, 1.057-1.251; P = 0.001)
      after initial resuscitation were associated with higher 28-day mortality. On the
      contrary, ScvO2 levels after resuscitation were not related to 28-day or hospital
      mortality. In conclusion, our results showed that mean arterial pressure and
      central venous pressure were still the most important hemodynamic variables in
      initial hemodynamic resuscitation. Low postresuscitation ScvO2 was not associated
      with a worse outcome. It is possible that ScvO2 less than 70% might not
      necessarily be associated with tissue hypoxia, and critical ScvO2 levels require
      to be determined by further studies.

PMID- 23143063
TI  - Interleukin-22 modulates gut epithelial and immune barrier functions following
      acute alcohol exposure and burn injury.
AB  - Interleukin-22 (IL-22) maintains gut epithelial integrity and expression of
      antimicrobial peptides Reg3beta and Reg3gamma. Our laboratory has shown that
      acute alcohol/ethanol (EtOH) exposure before burn injury results in increased gut
      permeability, intestinal T-cell suppression, and enhanced bacterial
      translocation. Herein, we determined the effect of combined EtOH intoxication and
      burn injury on intestinal levels of IL-22 as well as Reg3beta and Reg3gamma
      expression. We further examined whether in vivo restitution of IL-22 restores gut
      permeability, Reg3beta and Reg3gamma levels, and bacterial load (e.g., gut
      bacterial growth) within the intestine after EtOH and burn injury. Male mice,
      ~25g, were gavaged with EtOH (2.9 mg/kg) before receiving a ~12.5% total-body
      surface-area, full-thickness burn. Mice were immediately treated with saline
      control or IL-22 (1 mg/kg) by i.p. injection. One day after injury, there was a
      significant decrease in intestinal IL-22, Reg3beta, and Reg3gamma expression
      along with an increase in intestinal permeability and gut bacterial load after
      EtOH combined with burn injury, as compared with sham injury. Treatment with IL
      22 normalized Reg3beta and Reg3gamma expression and attenuated the increase in
      intestinal permeability after EtOH and burn injury. Qualitatively, IL-22
      treatment reduced the bacterial load in nearly half of mice receiving EtOH
      combined with burn injury. Our data indicate that IL-22 maintains gut epithelial
      and immune barrier integrity after EtOH and burn injury; thus, the IL
      22/antimicrobial peptide pathway may provide a therapeutic target for the
      treatment of patients who sustain burn injury under the influence of EtOH.

PMID- 23143065
TI  - Activation of a cyclic amp-guanine exchange factor in hepatocytes decreases
      nitric oxide synthase expression.
AB  - Adenosine 3',5'-cyclic adenosine monophosphate (cAMP) activates intracellular
      signaling by regulating protein kinase A, calcium influx, and cAMP-binging
      guanine nucleotide exchange factors (Epac [exchange protein directly activated by
      cAMP] or cAMP-GEF). Cyclic adenosine monophosphate inhibits cytokine-induced
      expression of inducible nitric oxide synthase (iNOS) in hepatocytes by a protein
      kinase A-independent mechanism. We hypothesized that Epac mediates this effect. A
      cyclic AMP analog that specifically activates Epac, 8-(4-methoxyphenylthio)-2'-O
      methyladenosine-3',5'-cyclic monophosphate (OPTmecAMP), and overexpression of
      liver-specific Epac2 both inhibited interleukin 1beta/interferon gamma-induced
      iNOS expression and nitrite production. OPTmecAMP inactivated Raf1/MEK/ERK
      signaling, but ERK had no effect on iNOS expression. OPTmecAMP induced a
      persistent Akt phosphorylation in hepatocytes that lasted up to 8 h.
      Overexpression of a dominant-negative Akt blocked the inhibitory effect of
      OPTmecAMP on iNOS production. A specific PI3K inhibitor, LY294002, attenuated the
      inhibition of nitrite production and iNOS expression produced by overexpressing a
      liver-specific Epac2 (LEpac2). OPTmecAMP also induced c-Jun N-terminal kinase
      (JNK) phosphorylation in hepatocytes. Overexpression of dominant-negative JNK
      enhanced cytokine-induced iNOS expression and nitrite production and reversed the
      inhibitory effects of LEpac2 on nitrite production and iNOS expression. We
      conclude that Epac regulates hepatocyte iNOS expression through an Akt- and JNK
      mediated signaling mechanism.

PMID- 23143066
TI  - Value of cardiac troponin I for predicting in-hospital occurrence of hypotension
      in stable patients with acute pulmonary embolism.
AB  - Although cardiac troponin I (cTnI) elevations during acute pulmonary embolism
      (PE) are predictive of in-hospital death, it is not clear whether cTnI
      measurements at emergency department (ED) admission are predictive of the
      occurrence of hypotension. The study subjects included all consecutive patients
      with acute PE (diagnosed by chest computed tomography angiography) in the ED
      between January 2006 and December 2011. All underwent cTnI tests at ED admission
      and were divided into two groups based on the occurrence of hypotension within 24
      h. Of 457 stable patients with acute PE who were admitted to the ED during the
      study period, 301 patients were included. Within 24 h of hospitalization, 27
      (9.0%) developed hypotension. The patients who developed hypotension had a
      significantly higher mean cTnI concentration than did the remaining patients
      (1.01 vs. 0.14 ng/mL, P < 0.00). They were also more likely to be treated with
      thrombolytic therapy and had higher 28-day and 6-month mortality rates. Cardiac
      TnI elevation (>0.05 ng/mL) at ED admission was a strong predictor of the
      development of hypotension within 24 h (odds ratio, 8.2; 95% confidence interval,
      2.6-26.1; P = 0.00). The sensitivity, specificity, positive predictive value, and
      negative predictive value of elevated cTnI were 85%, 66%, 20%, and 98%,
      respectively. This study suggests that a normal cTnI nearly rules out subsequent
      development of hypotension within 24 h. This may help to select those patients
      who would benefit most from intensive clinical surveillance and escalated
      treatment.

PMID- 23143067
TI  - Wnt agonist attenuates liver injury and improves survival after hepatic
      ischemia/reperfusion.
AB  - The Wnt/beta-catenin signaling pathway is well characterized in stem cell biology
      and plays a critical role in liver development, regeneration, and homeostasis. We
      hypothesized that pharmacologic activation of Wnt signaling protects against
      hepatic ischemia/reperfusion (I/R) injury through its known proliferative and
      antiapoptotic properties. Sprague-Dawley rats underwent 70% hepatic ischemia by
      microvascular clamping of the hilum of the left and median lobes of the liver for
      90 min, followed by reperfusion. Wnt agonist (2-amino-4-[3,4
      (methylenedioxy)benzylamino]-6-(3-methoxyphenyl)pyrimidine, 5 mg/kg body weight)
      or vehicle (20% dimethyl sulfoxide in saline) in 0.5 mL was injected i.p. 1 h
      before ischemia or infused i.v. over 30 min right after ischemia. Blood and
      tissue samples from the pretreated groups were collected 24 h after reperfusion,
      and a survival study was performed. Hepatic expression of beta-catenin and its
      downstream target gene Axin2 were decreased after I/R, whereas Wnt agonist
      restored their expression to sham levels. Wnt agonist blunted I/R-induced
      elevations of aspartate aminotransferase, alanine aminotransferase, and lactate
      dehydrogenase and significantly improved the microarchitecture of the liver. The
      cell proliferation determined by Ki67 immunostaining significantly increased with
      Wnt agonist treatment, and inflammatory cascades were dampened in Wnt agonist
      treated animals, as demonstrated by attenuations in interleukin 6,
      myeloperoxidase, inducible nitric oxide synthase, and nitrotyrosine. Wnt agonist
      also significantly decreased the amount of apoptosis, as evidenced by decreases
      in both TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling)
      staining as well as caspase 3 activity levels. Finally, the 10-day survival rate
      was increased from 27% in the vehicle group to 73% in the pretreated Wnt agonist
      group and 55% in the Wnt agonist postischemia treatment group. Thus, we propose
      that direct Wnt/beta-catenin stimulation may represent a novel therapeutic
      approach in the treatment of hepatic I/R.

PMID- 23143068
TI  - Infusion of Escherichia coli lipopolysaccharide toxin in rats produces an early
      and severe impairment of baroreflex function in absence of blood pressure
      changes.
AB  - The assessment of baroreflex function since the first appearance of endotoxemia
      is important because the arterial baroreflex should exert a protective role
      during sepsis. Nevertheless, contrasting results were previously reported. This
      could be due to the hemodynamic instability characterizing this condition that
      may per se interfere with reflex cardiovascular adjustments. The aim of our study
      was therefore to study the baroreflex function (a) since the very beginning of
      infusion of Escherichia coli lipopolysaccharide (LPS) toxin and (b) in absence of
      the unloading effect produced by a decrease in blood pressure. Lipopolysaccharide
      was infused in 10 rats for 20 min at the infusion rate of 0.05 mg . kg . min.
      Blood pressure was continuously measured before, during, and after infusion, and
      the baroreflex function was evaluated analyzing spontaneous fluctuations of
      systolic blood pressure and pulse interval by the sequence and transfer-function
      techniques. Plasma concentrations of inflammatory (interleukin 6, tumor necrosis
      factor alpha) and anti-inflammatory (interleukin 10) cytokines were measured in
      other eight rats, similarly instrumented, four of which receiving the same LPS
      infusion. We found that blood pressure levels did not change with the infusion of
      LPS, whereas inflammatory cytokines increased significantly. The baroreflex
      sensitivity was significantly reduced 10 min after the beginning of LPS infusion,
      reached values about half those at baseline within 15 min after the start of
      infusion, and remained significantly low after the end of infusion. In
      conclusion, we documented that septic shock inducing LPS infusion is responsible
      for a very rapid impairment of the baroreflex function, independent from the
      level of blood pressure.

PMID- 23143069
TI  - Hepatic gene expression patterns following trauma-hemorrhage:  effect of
      posttreatment with estrogen.
AB  - The aim of this study was to examine the role of estrogen on hepatic gene
      expression profiles at an early time point following trauma-hemorrhage in rats.
      Groups of injured and sham controls receiving estrogen or vehicle were killed 2 h
      after injury and resuscitation, and liver tissue was harvested. Complementary RNA
      was synthesized from each RNA sample and hybridized to microarrays. A large
      number of genes were differentially expressed at the 2-h time point in injured
      animals with or without estrogen treatment. The upregulation or downregulation of
      a cohort of 14 of these genes was validated by reverse transcription-polymerase
      chain reaction. This large-scale microarray analysis shows that at the 2-h time
      point, there is marked alteration in hepatic gene expression following trauma
      hemorrhage. However, estrogen treatment attenuated these changes in injured
      animals. Pathway analysis demonstrated predominant changes in the expression of
      genes involved in metabolism, immunity, and apoptosis. Upregulation of low
      density lipoprotein receptor, protein phosphatase 1, regulatory subunit 3C, ring
      finger protein 11, pyroglutamyl-peptidase I, bactericidal/permeability-increasing
      protein, integrin, alphaD, BCL2-like 11, leukemia inhibitory factor receptor,
      ATPase, Cu transporting, alpha polypeptide, and Mk1 protein was found in estrogen
      treated trauma-hemorrhaged animals. Thus, estrogen produces hepatoprotection
      following trauma-hemorrhage likely via antiapoptosis and improving/restoring
      metabolism and immunity pathways.

PMID- 23143070
TI  - Predictive validity of established cut points for risk and protective factor
      scales from the communities that care youth survey.
AB  - Community coalitions are a popular strategy to coordinate activities and
      resources to prevent adolescent substance use and delinquent behavior. Despite
      early evidence of their lack of effectiveness, a new generation of community
      coalitions has shown positive results in preventing youth substance use and
      delinquency. This success can be attributed to coalition decision making focused
      on reducing local risk factors and increasing local protective factors through
      the use of evidence-based prevention programs. A previous study using cross
      sectional data established cut point values for scales measuring risk and
      protective factors on the Communities That Care Youth Survey (CTCYS) to identify
      high levels of risk and low levels of protection in communities on each scale.
      The current study extended this previous research by using longitudinal data to
      assess the validity of risk and protective factor cut point values in predicting
      substance use and delinquent behavior 1 year after risk and protection were
      measured. The findings demonstrate the predictive validity of cut points for risk
      and protective factor scales measured by the CTCYS and suggest their utility in
      guiding prevention efforts.

PMID- 23143071
TI  - The development of videos in culturally grounded drug prevention for rural native
      Hawaiian youth.
AB  - The purpose of this study was to adapt and validate narrative scripts to be used
      for the video components of a culturally grounded drug prevention program for
      rural Native Hawaiian youth. Scripts to be used to film short video vignettes of
      drug-related problem situations were developed based on a foundation of pre
      prevention research funded by the National Institute on Drug Abuse. Seventy-four
      middle- and high-school-aged youth in 15 focus groups adapted and validated the
      details of the scripts to make them more realistic. Specifically, youth
      participants affirmed the situations described in the scripts and suggested
      changes to details of the scripts to make them more culturally specific.
      Suggested changes to the scripts also reflected preferred drug resistance
      strategies described in prior research, and varied based on the type of drug
      offerer described in each script (i.e., peer/friend, parent, or cousin/sibling).
      Implications for culturally grounded drug prevention are discussed.

PMID- 23143072
TI  - Sick building syndrome (SBS) and sick house syndrome (SHS) in relation to
      psychosocial stress at work in the Swedish workforce.
AB  - PURPOSE: Medical symptoms called sick building syndrome (SBS) and sick house
      syndrome (SHS) are usually investigated separately: in this study, SBS and SHS
      were explored simultaneously. The significance of personal factors, perceptions
      of air quality, and psychosocial work situation in explaining SBS and SHS were
      investigated. METHODS: A random sample of 1,000 subjects (20-65 year) received a
      postal questionnaire including questions on personal factors, medical symptoms,
      and the psychosocial demand-control-support model. The response rate was 70 % (n
      = 695), of which 532 were occupationally active. RESULTS: In logistic regression
      models, atopy, poor air quality at work, and low social support, especially low
      supervisor support, were associated with both SBS and SHS when age, gender,
      smoking, and BMI were introduced. The general work-related symptoms (headache,
      tiredness, nausea, and sensation of a cold) were also related to low control over
      work. CONCLUSIONS: The perception of poor physical environmental conditions is
      associated with common medical symptoms that are both work and home related. The
      associations between medical symptoms and poor air quality are still present,
      even when controlling for the psychosocial environment.

PMID- 23143073
TI  - Developmental abnormalities in Glomeris marginata (Villers 1789) (Myriapoda:
      Diplopoda): implications for body axis determination in a myriapod.
AB  - Abnormally developing embryos (ADEs) of the common pill millipede Glomeris
      marginata have been investigated by means of nuclear staining and mRNA in situ
      hybridization. It showed that all ADEs represent cases of Duplicitas posterior,
      which means that the posterior body pole is duplicated. The severity of the
      duplication ranges from duplicated posterior trunk segments in one specimen to an
      almost completely duplicated specimen that only shares the very anterior head
      region. Remarkably, none of the encountered ADEs represents a case of Duplicitas
      anterior (duplicated anterior pole) or a case of Duplicitas cruciata (cruciate
      duplication with two anterior and two posterior poles). This observation is
      discussed in the light of earlier reports on G. marginata ADEs that claim to have
      found these abnormalities. The lack of any other axial abnormality aside from D.
      posterior implies that early axis determination in G. marginata, and possibly
      myriapods in general, underlies the developmental mechanisms that prevent the
      formation of any other type of axial duplication. It is proposed that the
      formation of D. posterior-type embryos could be caused by the formation of two
      instead of only one posterior cumulus early during development.

PMID- 23143074
TI  - Correlation of mandibular impacted tooth and bone morphology determined by cone
      beam computed topography on a premise of third molar operation.
AB  - PURPOSE: To determine the width and morphology of the mandible in the impacted
      third molar region, and to identify the location of the mandibular canal prior to
      planning impacted third molar operations. METHODS: Cone beam computed tomography
      (CBCT) data of 87 mandibular third molars from 62 Japanese patients were analyzed
      in this study. The width of the lingual cortical bone and apex-canal distance
      were measured from cross-sectional images in which the cortical bone was thinnest
      at the lingual side in the third molar region. Images were used for measuring the
      space (distance between the inner border of the lingual cortical bone and outer
      surface of the third molar root), apex-canal distance (distance from the root of
      the third molar tooth to the superior border of the inferior alveolar canal) and
      the cortical bone (width between the inner and outer borders of the lingual
      cortical bone). RESULTS: The means of the space, apex-canal distance and lingual
      cortical width were 0.31, 1.99, and 0.68 mm, respectively. Impacted third molar
      teeth (types A-C) were observed at the following frequencies: type A (angular) 37
      %; type B (horizontal), 42 %; type C (vertical), 21 %. The morphology of the
      mandible at the third molar region (types D-F) was observed as: type D (round),
      49 %; type E (lingual extended), 18 %; and type F (lingual concave), 32 %.
      CONCLUSIONS: The width and morphology of the mandible with impacted teeth and the
      location of the mandibular canal at the third molar region could be clearly
      determined using cross-sectional CBCT images.

PMID- 23143075
TI  - Logging on: evaluating an online support group for parents of children with
      autism spectrum disorders.
AB  - Twenty mothers participated in an online support group for parents of children
      with autism spectrum disorders. Twenty-five unrelated parents participated in a
      no-treatment control group. The participants completed online questionnaires
      prior to and following the 4-month support group, to evaluate changes in mood,
      anxiety, parenting stress, and positive perceptions. No significant differences
      between the groups or across time were found. However, parents who participated
      in the group reported being satisfied with the support they received and finding
      the group helpful. Issues related to participant recruitment and retention are
      discussed. Further research is required to investigate the efficacy of online
      support groups for parents of children with ASD.

PMID- 23143076
TI  - Fourier transform infrared imaging as a tool to chemically and spatially
      characterize matrix-mineral deposition in osteoblasts.
AB  - Mineralizing osteoblasts are regularly used to study osteogenesis and model in
      vivo bone formation. Thus, it is important to verify that the mineral and matrix
      being formed in situ are comparable to those found in vivo. However, it has been
      shown that histochemical techniques alone are not sufficient for identifying
      calcium phosphate-containing mineral. The goal of the present study was to
      demonstrate the use of Fourier transform infrared imaging (FTIRI) as a tool for
      characterizing the spatial distribution and colocalization of the collagen matrix
      and the mineral phase during the mineralization process of osteoblasts in situ.
      MC3T3-E1 mouse osteoblasts were mineralized in culture for 28 days and FTIRI was
      used to evaluate the collagen content, collagen cross-linking, mineralization
      level and speciation, and mineral crystallinity in a spatially resolved fashion
      as a function of time. To test whether FTIRI could detect subtle changes in the
      mineralization process, cells were treated with risedronate (RIS). Results showed
      that collagen deposition and mineralization progressed over time and that the
      apatite mineral was associated with a collagenous matrix rather than ectopic
      mineral. The process was temporarily slowed by RIS, where the inhibition of
      osteoblast function caused slowed collagen production and cross-linking, leading
      to decreased mineralization. This study demonstrates that FTIRI is a
      complementary tool to histochemistry for spatially correlating the collagen
      matrix distribution and the nature of the resultant mineral during the process of
      osteoblast mineralization. It can further be used to detect small perturbations
      in the osteoid and mineral deposition process.

PMID- 23143077
TI  - Decreased pulmonary c-Cbl expression and tyrosine phosphorylation in the nitrofen
      induced rat model of congenital diaphragmatic hernia.
AB  - PURPOSE: The high morbidity of newborn infants with congenital diaphragmatic
      hernia (CDH) is attributed to pulmonary hypoplasia (PH), which is characterized
      by a failure of alveolar development. The nitrofen-induced CDH model has been
      widely used to investigate the pathogenesis of PH in CDH. It has previously been
      shown that the fibroblast growth factor receptor (FGFR) pathway, which is
      essential for a proper lung development, is disrupted during late gestation of
      nitrofen-induced CDH. Casitas B-lineage lymphoma (c-Cbl) proteins are known
      regulators of signal transduction through FGFRs, indicating their important role
      during alveolarization in developing lungs. Furthermore, it has been demonstrated
      that tyrosine phosphorylation of c-Cbl proteins has a pivotal role for their
      physiological function and activity during fetal lung development. We designed
      this study to test the hypothesis that pulmonary c-Cbl expression and tyrosine
      phosphorylation status are decreased in the nitrofen-induced CDH model. METHODS:
      Timed-pregnant rats received either 100 mg nitrofen or vehicle on gestation day 9
      (D9). Fetuses were harvested on D18 and D21, and lungs were divided into two
      groups: control and hypoplastic lungs with CDH (CDH(+)) (n = 10 at each time
      point, respectively). Pulmonary gene expression levels of c-Cbl were analyzed by
      quantitative real-time polymerase chain reaction. Western blotting combined with
      densitometry analysis was used for semi-quantification of protein levels of
      pulmonary c-Cbl and tyrosine phosphorylation status. Confocal-immunofluorescence
      staining was performed to evaluate c-Cbl protein expression and distribution.
      RESULTS: Relative mRNA expression levels of pulmonary c-Cbl were significantly
      decreased in CDH(+) on D18 and D21 compared to controls. Western blotting showed
      markedly decreased protein levels of pulmonary c-Cbl and tyrosine phosphorylation
      status in CDH(+) on D18 and D21. Confocal-immunofluorescence analysis confirmed
      decreased c-Cbl expression in CDH(+) on D18 and D21 mainly in the distal alveolar
      epithelium compared to controls. CONCLUSION: Decreased pulmonary c-Cbl gene and
      protein expression accompanied by a decreased tyrosine phosphorylation status
      during the late stages of fetal lung development may result in reduced c-Cbl
      activity, and thus interfere with the FGFR-mediated alveolarization in the
      nitrofen-induced CDH model.

PMID- 23143078
TI  - Abnormal control of lung branching in experimental esophageal atresia.
AB  - PURPOSE: Esophageal atresia and tracheo-esophageal fistula (EA-TEF) result from
      abnormal division of the foregut into esophagus and trachea thus, it may
      influence airway branching and lung development. The present study examined lung
      morphogenesis in fetuses with EA-TEF focusing in the expression of FGF10 and its
      receptor FGFR2 IIIb. METHODS: Pregnant rats received either 1.75 mg/kg i.p.
      adriamycin or vehicle on E7, E8 and E9. Embryos were recovered at E15, E18 and
      E21 and lungs processed for immunohistochemistry and RT-PCR. Three groups were
      studied: control, adriamycin-exposed with EA-TEF, and adriamycin-exposed without
      EA-TEF. Comparisons were performed with Mann-Whitney or t tests (significance
      level, 5 %). RESULTS: Lung weight at E15 and E18 were significantly lower in
      adriaEA fetuses in which the relative mRNA levels of FGF10 were significantly
      higher. These differences disappeared near term. The receptor FGFR2 IIIb
      messenger was only significantly increased in adria noEA fetuses at E15.
      Immunohistochemical study was consistent with these findings. CONCLUSIONS:
      Abnormal expression of FGF10 during earlier stages of development, when the lungs
      are smaller than controls, suggests a compensatory response aimed at "catching
      up" delayed tracheobronchial branching. Whether similar changes take place in the
      human condition and influence respiratory physiology remain to be determined.

PMID- 23143079
TI  - Anorectal neural crest derived cell behavior after the migration of vagal neural
      crest derived cells is surgically disrupted: implications for the etiology of
      Hirschsprung's disease.
AB  - BACKGROUND/PURPOSE: In Hirschsprung's disease (HD), thick extrinsic nerve fibers
      can be associated with the aganglionic segment in the anorectum. We surgically
      disrupted the migration of vagal neural crest cell-derived cells (vagal NCC) in
      embryos from transgenic mice we created previously (SOX10-VENUS Tg) which have
      the SOX10 gene labeled with Venus (V), a green fluorescent protein, to observe
      sacral NCC activity in the anorectum. METHOD: Proximal colon harvested from SOX10
      VENUS Tg embryos on day 10.5 (n = 10) was transected at the ascending colon. V
      positive sacral NCC in the anorectum were observed during organ culture under
      fluorescence stereoscopic microscopy, and compared with non-transected control
      specimens (n = 10). RESULTS: In transected specimens, no V-positive sacral NCC
      were identified initially in the anorectum. By day 2, there were thick beaded
      sacral NCC in the anorectum in 6/10 (60 %) that migrated steadily to the
      transected end over 3-4 days. In controls, thinner and shorter V-positive sacral
      NCC began migrating cranially on day 2, and were met by distally migrating vagal
      NCC. CONCLUSION: Disruption of vagal NCC migration appears to induce sacral NCC
      activity in the anorectum, suggesting that thick extrinsic nerve fibers seen in
      HD may be a secondary phenomenon.

PMID- 23143080
TI  - Open surgery is dead, long live endourology: is it always true? (Re: comparative
      analyses of percutaneous nephrolithotomy versus open surgery in pediatric urinary
      stone disease).

PMID- 23143081
TI  - The impact of training interventions on organizational readiness to support
      innovations in juvenile justice offices.
AB  - Clinical trials on technology transfer models are rare, even with the interest in
      advancing the uptake of evidence-based practices in social service agencies. This
      article presents the results from a trial examining different transfer strategies
      to assist juvenile justice caseworkers in using screening, assessment, and case
      planning practices to address mental health and substance use needs. Study
      findings examine factors that promote organizational readiness. A clinical trial
      was conducted examining the impact of three post-training strategies: an external
      coach to build the social network of the justice office (build social climate),
      an external coach to educate staff (build skills and knowledge), and a control
      condition consisting of traditional management directives (directives to staff of
      agency priorities). All groups were exposed to a 1 day refresher course in
      motivational interviewing. The social network and skill building groups also
      attended an intensive 3-day training followed by three on-site booster sessions
      over a 12 month period of time. Twelve juvenile justice offices (with their 231
      juvenile justice staff) were assigned to one of three conditions. The study
      examined the impact of different transfer conditions on organizational readiness
      to implement the innovation of screening, assessment, and referral strategies.
      External coaching targeting the social climate of the justice office to support
      innovations improved organizational readiness to change, regardless of office
      size. Coaching that targeted either the social climate or staff knowledge and
      skills both improved organizational readiness for change compared to management
      directives, but social climate coaching resulted in greater improvements in
      receptivity to change. No individual level features of case workers (e.g., age,
      gender, years of experience) significantly predicted organizational readiness to
      change. Unexpectedly, the skill and knowledge building approach did not perform
      any better than management directives only (no post training) efforts.
      Organizational readiness has been found to be an important factor supporting
      agencies' adoption of evidence-based practices. Techniques devoted to attending
      to the social climate are critical to increasing organizational readiness.
      External coach facilitators can accomplish this through modest means (three post
      training booster sessions) that build internal expertise and resiliency in
      support of the change. This is a low cost method of preparing a low resourced
      environment such as juvenile justice agencies to use evidence-based practices. 

PMID- 23143082
TI  - Towards a role of ultrasound in children with juvenile idiopathic arthritis.
AB  - US is a powerful tool for the assessment of joint synovitis in children with JIA
      and has been shown to be more accurate than clinical examination in detecting
      synovial disease. Recent studies have documented the presence of US-detected
      synovial pathology in children with JIA in clinical remission. US assessment
      enables the differentiation of joint synovitis from tenosynovitis, may help
      detect enthesitis and is valuable for capturing cartilage damage and early bone
      erosions. Guidance to local injection therapy represents an important application
      of US in routine care. Although US has a great potential for diffusion among
      paediatric rheumatologists, several issues need to be addressed. In particular, a
      thorough knowledge of US anatomy of joints in growing children is necessary to
      interpret US findings in JIA patients. The present review examines the potential
      role of US in the assessment of joint disease in children with JIA.

PMID- 23143083
TI  - Gastric aspiration is not necessary for the diagnosis of pulmonary tuberculosis.
AB  - Despite recommendations, gastric aspirate collected by invasive nasogastric
      aspiration is still routinely used for the direct detection of Mycobacterium
      tuberculosis in our institution. Reviewing 82 patients with culture-proven
      respiratory tuberculosis over a 28-month period, we observed no patient diagnosed
      solely by gastric aspirate analysis. Moreover, the diagnosis yield of gastric
      aspirate (60 %) did not significantly differ from that of stool specimen (64 %).
      These data confirm that gastric aspirate is no longer useful for the diagnosis of
      respiratory tuberculosis contrary to stool specimen.

PMID- 23143084
TI  - Original beta,gamma-diamino acid as an inducer of a gamma-turn mimic in short
      peptides.
AB  - Original alphagammaalpha tripeptides containing one beta,gamma-diamino acid have
      been synthesized and their conformation determined by extensive NMR and molecular
      dynamic studies. These studies revealed the presence of a C(9) hydrogen bonded
      turn around the beta,gamma-diamino acid which was stabilized by bulky side chains
      of the preceding residue. This turn can be considered as a mimic of the well
      known gamma-turn.

PMID- 23143085
TI  - Perioperative coagulation management in the intensive care unit.
AB  - PURPOSE OF REVIEW: Coagulopathy in an ICU setting is multifactorial, but newer
      anticoagulation agents are the potentially contributing causes. Critically ill
      patients may suffer from disorders because of surgery or trauma, in addition to
      acquired causes including antiplatelet agents and the new oral anticoagulants. An
      understanding of the coagulopathy, hemostatic considerations, and therapeutic
      approaches is important when managing these patients. RECENT FINDINGS: All
      anticoagulation agents may contribute to coagulopathy in critically ill patients.
      Options for management include hemodialysis, transfusion of blood products, and
      prohemostatic drugs. Recombinant and purified coagulation therapies are also now
      available in most countries that provide clinicians with specific agents to treat
      targeted deficiencies. SUMMARY: Coagulopathy occurs in ICU patients because of
      multiple factors including anticoagulants, dilution, fibrinolysis, and factor
      consumption. Therapeutic prohemostatic pharmacologic approaches, in addition to
      standard transfusion therapy, need to be considered in managing coagulopathy in
      the ICU setting.

PMID- 23143087
TI  - On the importance of image gating for the assay of left ventricular mechanical
      dyssynchrony using SPECT.
AB  - The potential of SPECT for quantifying left ventricular mechanical dyssynchrony
      is increasingly appreciated. We sought to examine the incidence and impact of
      image gating errors on this quantification and to test a possible solution for
      affected studies. METHODS: First, to establish whether and how gating error alone
      could affect the measurement of dyssynchrony, we performed a prospective study in
      which patients with pacemakers were studied twice: during normal rhythm without
      gating error and with gating error caused by pacemaker-induced dysrhythmia.
      Second, to understand the pattern and magnitude of gating error during our
      typical imaging practice, we retrospectively examined studies from a separate
      cohort of 64 patients who were referred for dyssynchrony evaluation. Third, to
      understand whether studies with gating error could be repaired for the purpose of
      quantifying dyssynchrony, we tested a correction algorithm on the pacemaker
      induced dysrhythmia image set to see whether it repaired this set so as to
      approximate the patients' normal rhythm image data. We subsequently applied this
      algorithm to the 64-patient cohort. RESULTS: Pacemaker-induced gating error
      caused a spurious decrease in dyssynchrony magnitude. Among the 64-patient
      cohort, similar gating errors were common, and an inverse exponential
      relationship between gating-error magnitude and dyssynchrony magnitude was
      observed. The correction algorithm accurately repaired the pacemaker-induced
      dysrhythmia image set; when it was applied to the 64-patient cohort, the
      magnitude of the postcorrection increase in dyssynchrony magnitude was
      proportional to the magnitude of the gating error. CONCLUSION: Gating errors
      cause a spurious reduction in SPECT assay of dyssynchrony magnitude. In our
      standard imaging practice, gating errors were common. Post hoc correction appears
      to be feasible.

PMID- 23143086
TI  - PET/MRI for neurologic applications.
AB  - PET and MRI provide complementary information in the study of the human brain.
      Simultaneous PET/MRI data acquisition allows the spatial and temporal correlation
      of the measured signals, creating opportunities impossible to realize using stand
      alone instruments. This paper reviews the methodologic improvements and potential
      neurologic and psychiatric applications of this novel technology. We first
      present methods for improving the performance and information content of each
      modality by using the information provided by the other technique. On the PET
      side, we discuss methods that use the simultaneously acquired MRI data to improve
      the PET data quantification. On the MRI side, we present how improved PET
      quantification can be used to validate several MRI techniques. Finally, we
      describe promising research, translational, and clinical applications that can
      benefit from these advanced tools.

PMID- 23143088
TI  - Altered GABAA receptor density and unaltered blood-brain barrier transport in a
      kainate model of epilepsy: an in vivo study using 11C-flumazenil and PET.
AB  - The aim of the present study was to investigate if flumazenil blood-brain barrier
      transport and binding to the benzodiazepine site on the gamma-aminobutyric acid A
      (GABA(A)) receptor complex is altered in an experimental model of epilepsy and
      subsequently to study if changes in P-glycoprotein (P-gp)-mediated efflux of
      flumazenil at the blood-brain barrier may confound interpretation of (11)C
      flumazenil PET in epilepsy. METHODS: The transport of flumazenil across the blood
      brain barrier and the binding to the benzodiazepine site on the GABA(A) receptors
      in 5 different brain regions was studied and compared between controls and
      kainate-treated rats, a model of temporal lobe epilepsy, with and without
      tariquidar pretreatment. In total, 29 rats underwent 2 consecutive (11)C
      flumazenil PET scans, each one lasting 30 min. The tracer was mixed with
      different amounts of isotopically unmodified flumazenil (4, 20, 100, or 400 MUg)
      to cover a wide range of receptor occupancies during the scan. Before the second
      scan, the rats were pretreated with a 3 or 15 mg/kg dose of the P-gp inhibitor
      tariquidar. The second scan was then obtained according to the same protocol as
      the first scan. RESULTS: GABA(A) receptor density, B(max), was estimated as 44 +/
      2 ng x mL(-1) in the hippocampus and as 33 +/- 2 ng x mL(-1) in the cerebellum,
      with intermediate values in the occipital cortex, parietal cortex, and caudate
      putamen. B(max) was decreased by 12% in kainate-treated rats, compared with
      controls. The radiotracer equilibrium dissociation constant, K(D), was similar in
      both rat groups and all brain regions and was estimated as 5.9 +/- 0.9 ng x mL(
      1). There was no difference in flumazenil transport across the blood-brain
      barrier between control and kainate-treated rats, and the effect of tariquidar
      treatment was similar in both rat groups. Tariquidar treatment also decreased
      flumazenil transport out of the brain by 73%, increased the volume of
      distribution in the brain by 24%, and did not influence B(max) or K(D), compared
      with baseline. CONCLUSION: B(max) was decreased in kainate-treated rats, compared
      with controls, but no alteration in the blood-brain barrier transport of
      flumazenil was observed. P-gp inhibition by tariquidar treatment increased brain
      concentrations of flumazenil in both groups, but B(max) estimates were not
      influenced, suggesting that (11)C-flumazenil scanning is not confounded by
      alterations in P-gp function.

PMID- 23143089
TI  - Differences in the biologic activity of 2 novel MEK inhibitors revealed by 18F
      FDG PET: analysis of imaging data from 2 phase I trials.
AB  - Two mitogen-activated protein kinase kinase (MAPK2, also known as MEK) inhibitors
      were assessed with (18)F-FDG PET in separate phase I clinical studies, clearly
      illustrating the potential of metabolic imaging for dose, dosing regimen, and
      compound selection in early-phase trials and utility for predicting nonresponding
      patients. METHODS: (18)F-FDG PET data were collected during 2 independent, phase
      I, dose-escalation trials of 2 novel MEK inhibitors (RO5126766 and RO4987655).
      PET acquisition procedures were standardized between the 2 trials, and PET images
      were analyzed centrally. Imaging was performed at baseline; at cycle 1, day 15;
      and at cycle 3, day 1. A 10-mm-diameter region of interest was defined for up to
      5 lesions, and peak standardized uptake values were determined for each lesion.
      The relationship between PET response and pharmacokinetic factors (dose and
      exposure), inhibition of extracellular-signal-regulated kinase (ERK)
      phosphorylation in peripheral blood mononuclear cells, and anatomic tumor
      response as measured by Response Evaluation Criteria in Solid Tumors was
      investigated for both compounds. RESULTS: Seventy-six patients underwent PET, and
      205 individual PET scans were analyzed. Strong evidence of biologic activity was
      seen as early as cycle 1, day 15, for both compounds. (18)F-FDG PET revealed
      striking differences between the 2 MEK inhibitors at their recommended dose for
      phase II investigation. The mean amplitude of the decrease in (18)F-FDG from
      baseline to cycle 1, day 15, was greater for patients receiving RO4987655 than
      for those receiving RO5126766 (47% vs. 16%, respectively; P = 0.052).
      Furthermore, a more pronounced relationship was seen between the change in (18)F
      FDG uptake and dose or exposure and phosphorylated ERK inhibition in peripheral
      blood mononuclear cells in patients receiving RO4987655. For both investigational
      drugs, PET responses tended to be greatest in patients with melanoma tumors.
      (18)F-FDG was able to identify early nonresponding patients with a 97% negative
      predictive value. CONCLUSION: These data exemplify the role of (18)F-FDG PET for
      guiding the selection of novel investigational drugs, choosing dose in early
      phase clinical development, and predicting nonresponding patients early in
      treatment.

PMID- 23143090
TI  - In vivo tracking techniques for cellular regeneration, replacement, and
      redirection.
AB  - Cellular therapy can be defined as the transplantation of living cells for the
      treatment of medical conditions. Three main objectives of cellular therapy are
      regeneration of damaged tissue, replacement of function by secretion of
      biologically active molecules, and redirection of aberrant processes. Given the
      complex nature of these approaches, in vivo tracking of the transplanted cells is
      critical to evaluate their potential benefit and to optimize treatment
      strategies. Recent advances are reviewed that enable in vivo cell tracking as an
      important adjunct to implement cellular therapy in clinical practice.

PMID- 23143091
TI  - Magnetic resonance imaging signal changes of alar and transverse ligaments not
      correlated with whiplash-associated disorders: a meta-analysis of case-control
      studies.
AB  - PURPOSE: Hypothesis that loss of integrity of the membranes in the craniocervical
      junction might be the cause of neck pain in patients with whiplash-associated
      disorders (WADs) has been proposed. In recent years, with development of more
      detailed magnetic resonance imaging (MRI) techniques, morphologic changes of the
      ligaments and membranes in the craniocervical junction, especially alar and
      transverse ligaments have been discussed. A meta-analysis was performed to
      evaluate the relationship of MRI signal changes of alar and transverse ligaments
      and WADs. METHODS: A systematic search of EMBASE, PUBMED, and Cochrane Library
      and references from eligible articles were conducted. Comparative studies
      reporting on evaluating the relationship between MRI high-signal changes of alar
      and transverse ligaments and WADs were regarded eligible. A pooled estimate of
      effect size was produced. RESULTS: Alar ligaments: Six studies (total n = 622)
      were included. MRI signal changes of alar ligaments did not appear to be related
      with WADs (P = 0.20, OR = 1.54, 95 % CI = 0.80-2.94). Heterogeneity was present
      (I (2) = 46 %, P = 0.10), which was eliminated upon sensitivity analysis bringing
      the OR to 1.27 (95 % CI = 0.87-1.86, I (2) = 0 %). Transverse ligaments: Four
      studies (total n = 489) were included. MRI signal changes of transverse ligament
      did not appear to be related with WADs (P = 0.51, OR = 1.44, 95 % CI = 0.49
      4.21). Heterogeneity was present (I (2) = 77 %, P = 0.005), which was eliminated
      upon sensitivity analysis bringing the OR to 0.79 (95 % CI = 0.49-1.28, I (2) = 0
      %). CONCLUSION: MRI signal changes of alar and transverse ligaments are not
      supposed to be caused by whiplash injury, and MRI examination of alar and
      transverse ligaments should not be used as the routine workup of patients with
      WADs.

PMID- 23143092
TI  - Indication for preoperative MRI of neural axis abnormalities in patients with
      presumed thoracolumbar/lumbar idiopathic scoliosis.
AB  - PURPOSE: The purpose of this study was to investigate the incidence of neural
      axis abnormalities in patients with presumed "idiopathic" thoracolumbar or lumbar
      scoliosis by magnetic resonance imaging (MRI) and try to determine which clinical
      and radiographic characteristics correlate with neural axis abnormalities on MRI
      in these patients. METHODS: The database of a single spinal deformity center was
      retrospectively reviewed to identify all patients with a primary diagnosis of
      idiopathic scoliosis (IS) between January 2003 and August 2011. A total of 446
      patients with main thoracolumbar or lumbar curves were identified. Radiographic
      parameters including main curve Cobb angles, location of curve apex, span of main
      curve, thoracic kyphosis (T5-T12), thoracolumbar junction kyphosis (T10-L2),
      lumbar lordosis (L1-S1), and sagittal and coronal balance were measured. RESULTS:
      Neural axis abnormalities were detected in 35 (7.8 %) patients. For patients with
      neural axis abnormalities, a higher proportion of male gender and long
      thoracolumbar curves were presented. In these patients, the mean age was smaller
      and the mean Cobb angle of main curve was larger. Greater thoracic kyphosis (>=
      30 degrees ) was more frequently found in those with neural axis abnormalities.
      The incidences of thoracolumbar junction hyperkyphosis were similar between two
      groups (P > 0.05). There was no difference between two groups as to lumbar
      lordosis and coronal and sagittal balance. CONCLUSION: We recommend the routine
      use of MRI in the patients with one or more of the following characteristics:
      right curves, long curve span, apex at thoracolumbar spine and hyperthoracic
      kyphosis.

PMID- 23143093
TI  - Effects of a postural education program on school backpack habits related to low
      back pain in children.
AB  - PURPOSE: Population based studies have demonstrated that children and adolescents
      often complain of low back pain. A group-randomized controlled trial was carried
      out to investigate the effects of a postural education program on school backpack
      habits related to low back pain in children aged 10-12 year. METHODS: The study
      sample included 137 children aged 10.7 years (SD = 0.672). Six classes from two
      primary schools were randomly allocated into experimental group (EG) (N = 63) or
      control group (CG) (N = 74). The EG received a postural education program over 6
      weeks consisting of six sessions, while the CG followed the usual school
      curriculum. A questionnaire was fulfilled by the participants at pre-test, post
      test, and 3 months after the intervention finished. The outcomes collected were:
      (1) try to load the minimum weight possible, (2) carry school backpack on two
      shoulders, (3) belief that school backpack weight does not affect to the back,
      and (4) the use of locker or something similar at school. A sum score was
      computed from the four items. RESULTS: Single healthy items mostly improved after
      the intervention and remained improved after 3-month follow-up in EG, while no
      substantial changes were observed in the CG. Healthy backpack use habits score
      was significantly increased at post-test compared to baseline in the EG (P <
      0.000), and remained significantly increased after 3-month, compared to baseline
      (P = 0.001). No significant changes were observed in the CG (P > 0.2).
      CONCLUSIONS: The present study findings confirm that children are able to learn
      healthy backpack habits which might prevent future low back pain.

PMID- 23143094
TI  - Treatment of spinal epidural compression due to hematological malignancies: a
      single institution's retrospective experience.
AB  - PURPOSE: To analyze the neurological and mechanical outcomes in 44 consecutive
      patients treated for a hematological malignancy with epidural localization to
      assess the place of surgery in the treatment of this pathology. METHODS: Clinical
      records, CT and MRI scans of 44 patients with epidural localizations of multiple
      myeloma or lymphoma treated between 1990 and 2005 were analyzed retrospectively.
      Neurological status, epiduritis and osteolysis volumes, vertebral collapse, and
      spinal canal compromise were assessed. The neurological outcome was graded
      according to Frankel and the mechanical outcome was evaluated on the rate of
      vertebral collapse. RESULTS: Surgery was performed in 11 patients (25 %) for
      neurological (n = 9) or mechanical (n = 2) reasons. In five cases, a concomitant
      biopsy was performed because the etiology of the epiduritis was unknown. Fifteen
      patients (34.1 %) presented with a neurological deficit secondary to an acute
      vertebral collapse (n = 4), an epiduritis (n = 7), or both (n = 4). Whatever the
      treatment (surgical or not), a complete recovery (Frankel E) occurred in 14/15
      (93.3 %) after a mean delay of 12 weeks (range 2-24 weeks). During the follow-up,
      seven collapses occurred. We estimated that a threshold of 30 % of osteolysis was
      associated with a significant risk of vertebral collapse (P = 0.005).
      CONCLUSIONS: Hematological malignancies with epidural localization must be
      treated first medically, even in patients with neurological symptoms. Surgery
      should be considered only in the cases of acute vertebral collapse, medical
      treatment failure, or to prevent acute collapse in patients with vertebral
      osteolysis of more than 30 %.

PMID- 23143095
TI  - Candida glabrata sepsis associated with chorioamnionitis in an in vitro
      fertilization pregnancy: case report and review.
AB  - We report a case of Candida glabrata sepsis associated with chorioamnionitis in
      an in vitro fertilization-assisted pregnancy. There is a strong association
      between C. glabrata chorioamnionitis and assisted fertility techniques. Candida
      glabrata chorioamnionitis presents unique management challenges.

PMID- 23143096
TI  - Association between tenofovir exposure and reduced kidney function in a cohort of
      HIV-positive patients: results from 10 years of follow-up.
AB  - BACKGROUND: Some studies have shown that tenofovir disoproxil fumarate (TDF), a
      drug widely used in highly active antiretroviral therapy, is associated with
      kidney dysfunction, but the magnitude of the effect and its clinical impact is
      still being debated. Our objective was to evaluate the association between long
      term TDF exposure and kidney dysfunction in a cohort of 1043 human
      immunodeficiency virus-positive patients followed up for 10 years and to quantify
      the loss in estimated glomerular filtration rate (eGFR) in patients exposed to
      TDF in comparison with those exposed to other antiretroviral therapies. METHODS:
      Adjusted hazard ratios (HR) and odds ratios (OR) for the association between TDF
      and kidney dysfunction (defined as eGFR <90 mL/min/1.73 m(2)) were calculated
      using the Cox proportional hazards model and generalized estimating equations.
      Mean loss in eGFR attributable to TDF by cumulative years of exposure was
      estimated using linear regressions. RESULTS: Tenofovir exposure increased the
      risk of kidney dysfunction by 63% (HR, 1.63; 95% confidence interval, 1.26-2.10).
      The cumulative eGFR loss directly attributable to TDF after 1, 2, 3, and 4 years
      of TDF exposure was -3.05 (P = .017), -4.05 (P = .000), -2.42 (P = .023), and 
      3.09 mL/min/1.73 m(2) (P = .119), respectively, which shows that most of the loss
      occurred during the first years of exposure. CONCLUSIONS: In this cohort, TDF
      exposure was associated with reduced kidney function, but the loss in eGFR
      attributable to TDF is relatively mild in a long-term perspective.

PMID- 23143098
TI  - Surgical care improvement project performance measures: good but not perfect.

PMID- 23143099
TI  - Surgical care improvement project in the value-based purchasing era: more harm
      than good?
AB  - The Surgical Care Improvement Project (SCIP) started in 2006 as a core measure to
      reduce perioperative morbidity and mortality, with many measures addressing
      perioperative antibiotic usage and timing. However, measures are often rolled out
      without consideration of their full impact, causing confusion, frustration, and
      possibly patient harm. We have provided examples of each. The institution of SCIP
      has markedly increased the compliance to its measures but little evidence shows
      that it provides any substantial benefit to patients, whereas this improved
      compliance comes at the cost of significant time, money, and staff resources.
      Despite this, several SCIP measures, which are currently incorporated into
      quality contracts, will be tied to Medicare reimbursement in 2013 under value
      based purchasing, with third-party payers likely following suit. This may lead to
      inappropriate lower compensation of hospitals providing good care with
      questionable effects on patient outcomes.

PMID- 23143100
TI  - Differential activation and functional specialization of miR-146 and miR-155 in
      innate immune sensing.
AB  - Many microRNAs (miRNAs) are co-regulated during the same physiological process
      but the underlying cellular logic is often little understood. The conserved,
      immunomodulatory miRNAs miR-146 and miR-155, for instance, are co-induced in many
      cell types in response to microbial lipopolysaccharide (LPS) to feedback-repress
      LPS signalling through Toll-like receptor TLR4. Here, we report that these
      seemingly co-induced regulatory RNAs dramatically differ in their induction
      behaviour under various stimuli strengths and act non-redundantly through
      functional specialization; although miR-146 expression saturates at sub
      inflammatory doses of LPS that do not trigger the messengers of inflammation
      markers, miR-155 remains tightly associated with the pro-inflammatory
      transcriptional programmes. Consequently, we found that both miRNAs control
      distinct mRNA target profiles; although miR-146 targets the messengers of LPS
      signal transduction components and thus downregulates cellular LPS sensitivity,
      miR-155 targets the mRNAs of genes pervasively involved in pro-inflammatory
      transcriptional programmes. Thus, miR-155 acts as a broad limiter of pro
      inflammatory gene expression once the miR-146 dependent barrier to LPS triggered
      inflammation has been breached. Importantly, we also report alternative miR-155
      activation by the sensing of bacterial peptidoglycan through cytoplasmic NOD-like
      receptor, NOD2. We predict that dose-dependent responses to environmental stimuli
      may involve functional specialization of seemingly co-induced miRNAs in other
      cellular circuitries as well.

PMID- 23143101
TI  - Genetic interactions suggest multiple distinct roles of the arch and core
      helicase domains of Mtr4 in Rrp6 and exosome function.
AB  - The RNA exosome is responsible for a wide variety of RNA processing and
      degradation reactions. The activity and specificity of the RNA exosome is thought
      to be controlled by a number of cofactors. Mtr4 is an essential RNA-dependent
      adenosine triphosphatase that is required for all of the nuclear functions of the
      RNA exosome. The crystal structure of Mtr4 uncovered a domain that is conserved
      in the RNA exosome cofactors Mtr4 and Ski2 but not in other helicases, suggesting
      it has an important role related to exosome activation. Rrp6 provides the nuclear
      exosome with one of its three nuclease activities, and previous findings
      suggested that the arch domain is specifically required for Rrp6 functions. Here,
      we report that the genetic interactions between the arch domain of Mtr4 and Rrp6
      cannot be explained by the arch domain solely acting in Rrp6-dependent processing
      reactions. Specifically, we show that the arch domain is not required for all
      Rrp6 functions, and that the arch domain also functions independently of Rrp6.
      Finally, we show that the arch domain of Ski2, the cytoplasmic counterpart of
      Mtr4, is required for Ski2's function, thereby confirming that the arch domains
      of these cofactors function independently of Rrp6.

PMID- 23143102
TI  - Genomic deletion induced by Tol2 transposon excision in zebrafish.
AB  - Genomic deletions induced by imprecise excision of transposons have been used to
      disrupt gene functions in Drosophila. To determine the excision properties of
      Tol2, a popular transposon in zebrafish, we took advantage of two transgenic
      zebrafish lines Et(gata2a:EGFP)pku684 and Et(gata2a:EGFP)pku760, and mobilized
      the transposon by injecting transposase mRNA into homozygous transgenic embryos.
      Footprint analysis showed that the Tol2 transposons were excised in either a
      precise or an imprecise manner. Furthermore, we identified 1093-bp and 1253-bp
      genomic deletions in Et(gata2a:EGFP)pku684 founder embryos flanking the 5' end of
      the original Tol2 insertion site, and a 1340-bp deletion in the
      Et(gata2a:EGFP)pku760 founder embryos flanking the 3' end of the insertion site.
      The mosaic Et(gata2a:EGFP)pku684 embryos were raised to adulthood and screened
      for germline transmission of Tol2 excision in their F(1) progeny. On average,
      ~42% of the F(1) embryos displayed loss or altered EGFP patterns, demonstrating
      that this transposon could be efficiently excised from the zebrafish genome in
      the germline. Furthermore, from 59 founders, we identified one that transmitted
      the 1093-bp genomic deletion to its offspring. These results suggest that
      imprecise Tol2 transposon excision can be used as an alternative strategy to
      achieve gene targeting in zebrafish.

PMID- 23143103
TI  - Mechanism of promoter repression by Lac repressor-DNA loops.
AB  - The Escherichia coli lactose (lac) operon encodes the first genetic switch to be
      discovered, and lac remains a paradigm for studying negative and positive control
      of gene expression. Negative control is believed to involve competition of RNA
      polymerase and Lac repressor for overlapping binding sites. Contributions to the
      local Lac repressor concentration come from free repressor and repressor
      delivered to the operator from remote auxiliary operators by DNA looping. Long
      standing questions persist concerning the actual role of DNA looping in the
      mechanism of promoter repression. Here, we use experiments in living bacteria to
      resolve four of these questions. We show that the distance dependence of
      repression enhancement is comparable for upstream and downstream auxiliary
      operators, confirming the hypothesis that repressor concentration increase is the
      principal mechanism of repression loops. We find that as few as four turns of DNA
      can be constrained in a stable loop by Lac repressor. We show that RNA polymerase
      is not trapped at repressed promoters. Finally, we show that constraining a
      promoter in a tight DNA loop is sufficient for repression even when promoter and
      operator do not overlap.

PMID- 23143104
TI  - Vika/vox, a novel efficient and specific Cre/loxP-like site-specific
      recombination system.
AB  - Targeted genome engineering has become an important research area for diverse
      disciplines, with site-specific recombinases (SSRs) being among the most popular
      genome engineering tools. Their ability to trigger excision, integration,
      inversion and translocation has made SSRs an invaluable tool to manipulate DNA in
      vitro and in vivo. However, sophisticated strategies that combine different SSR
      systems are ever increasing. Hence, the demand for additional precise and
      efficient recombinases is dictated by the increasing complexity of the genetic
      studies. Here, we describe a novel site-specific recombination system designated
      Vika/vox. Vika originates from a degenerate bacteriophage of Vibrio
      coralliilyticus and shares low sequence similarity to other tyrosine
      recombinases, but functionally carries out a similar type of reaction. We
      demonstrate that Vika is highly specific in catalyzing vox recombination without
      recombining target sites from other SSR systems. We also compare the
      recombination activity of Vika/vox with other SSR systems, providing a guideline
      for deciding on the most suitable enzyme for a particular application and
      demonstrate that Vika expression does not cause cytotoxicity in mammalian cells.
      Our results show that Vika/vox is a novel powerful and safe instrument in the
      'genetic toolbox' that can be used alone or in combination with other SSRs in
      heterologous hosts.

PMID- 23143105
TI  - MonarchBase: the monarch butterfly genome database.
AB  - The monarch butterfly (Danaus plexippus) is emerging as a model organism to study
      the mechanisms of circadian clocks and animal navigation, and the genetic
      underpinnings of long-distance migration. The initial assembly of the monarch
      genome was released in 2011, and the biological interpretation of the genome
      focused on the butterfly's migration biology. To make the extensive data
      associated with the genome accessible to the general biological and lepidopteran
      communities, we established MonarchBase (available at
      http://monarchbase.umassmed.edu). The database is an open-access, web-available
      portal that integrates all available data associated with the monarch butterfly
      genome. Moreover, MonarchBase provides access to an updated version of genome
      assembly (v3) upon which all data integration is based. These include genes with
      systematic annotation, as well as other molecular resources, such as brain
      expressed sequence tags, migration expression profiles and microRNAs. MonarchBase
      utilizes a variety of retrieving methods to access data conveniently and for
      integrating biological interpretations.

PMID- 23143106
TI  - EcoCyc: fusing model organism databases with systems biology.
AB  - EcoCyc (http://EcoCyc.org) is a model organism database built on the genome
      sequence of Escherichia coli K-12 MG1655. Expert manual curation of the functions
      of individual E. coli gene products in EcoCyc has been based on information found
      in the experimental literature for E. coli K-12-derived strains. Updates to
      EcoCyc content continue to improve the comprehensive picture of E. coli biology.
      The utility of EcoCyc is enhanced by new tools available on the EcoCyc web site,
      and the development of EcoCyc as a teaching tool is increasing the impact of the
      knowledge collected in EcoCyc.

PMID- 23143107
TI  - ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA
      sequencing data.
AB  - Chimeric RNAs that comprise two or more different transcripts have been
      identified in many cancers and among the Expressed Sequence Tags (ESTs) isolated
      from different organisms; they might represent functional proteins and produce
      different disease phenotypes. The ChiTaRS database of Chimeric Transcripts and
      RNA-Sequencing data (http://chitars.bioinfo.cnio.es/) collects more than 16 000
      chimeric RNAs from humans, mice and fruit flies, 233 chimeras confirmed by RNA
      seq reads and ~2000 cancer breakpoints. The database indicates the expression and
      tissue specificity of these chimeras, as confirmed by RNA-seq data, and it
      includes mass spectrometry results for some human entries at their junctions.
      Moreover, the database has advanced features to analyze junction consistency and
      to rank chimeras based on the evidence of repeated junction sites. Finally,
      'Junction Search' screens through the RNA-seq reads found at the chimeras'
      junction sites to identify putative junctions in novel sequences entered by
      users. Thus, ChiTaRS is an extensive catalog of human, mouse and fruit fly
      chimeras that will extend our understanding of the evolution of chimeric
      transcripts in eukaryotes and can be advantageous in the analysis of human cancer
      breakpoints.

PMID- 23143108
TI  - DNA expansions generated by human PolMU on iterative sequences.
AB  - Polu is the only DNA polymerase equipped with template-directed and terminal
      transferase activities. Polu is also able to accept distortions in both primer
      and template strands, resulting in misinsertions and extension of realigned
      mismatched primer terminus. In this study, we propose a model for human Polu
      mediated dinucleotide expansion as a function of the sequence context. In this
      model, Polu requires an initial dislocation, that must be subsequently
      stabilized, to generate large sequence expansions at different 5'-P-containing
      DNA substrates, including those that mimic non-homologous end-joining (NHEJ)
      intermediates. Our mechanistic studies point at human Polu residues His(329) and
      Arg(387) as responsible for regulating nucleotide expansions occurring during DNA
      repair transactions, either promoting or blocking, respectively, iterative
      polymerization. This is reminiscent of the role of both residues in the mechanism
      of terminal transferase activity. The iterative synthesis performed by Polu at
      various contexts may lead to frameshift mutations producing DNA damage and
      instability, which may end in different human disorders, including cancer or
      congenital abnormalities.

PMID- 23143109
TI  - HemaExplorer: a database of mRNA expression profiles in normal and malignant
      haematopoiesis.
AB  - The HemaExplorer (http://servers.binf.ku.dk/hemaexplorer) is a curated database
      of processed mRNA Gene expression profiles (GEPs) that provides an easy display
      of gene expression in haematopoietic cells. HemaExplorer contains GEPs derived
      from mouse/human haematopoietic stem and progenitor cells as well as from more
      differentiated cell types. Moreover, data from distinct subtypes of human acute
      myeloid leukemia is included in the database allowing researchers to directly
      compare gene expression of leukemic cells with those of their closest normal
      counterpart. Normalization and batch correction lead to full integrity of the
      data in the database. The HemaExplorer has comprehensive visualization interface
      that can make it useful as a daily tool for biologists and cancer researchers to
      assess the expression patterns of genes encountered in research or literature.
      HemaExplorer is relevant for all research within the fields of leukemia,
      immunology, cell differentiation and the biology of the haematopoietic system.

PMID- 23143111
TI  - Underutilized ultrasound applications in the neonatal intensive care unit.
AB  - Bedside duplex/color Doppler sonography is used for a wide gamut of abnormalities
      encountered in the neonatal intensive care unit. This article emphasizes the use
      of bedside sonography for evaluation of infants with necrotizing enterocolitis,
      infants requiring line placement, and those in whom a diaphragmatic abnormality
      is suspected. Although the assessment of those infants requires excellent
      operator skills, learning to do so is a definite benefit to these babies who
      would otherwise be exposed to ionizing radiation.

PMID- 23143110
TI  - Single-molecule kinetics reveal microscopic mechanism by which High-Mobility
      Group B proteins alter DNA flexibility.
AB  - Eukaryotic High-Mobility Group B (HMGB) proteins alter DNA elasticity while
      facilitating transcription, replication and DNA repair. We developed a new single
      molecule method to probe non-specific DNA interactions for two HMGB homologs: the
      human HMGB2 box A domain and yeast Nhp6Ap, along with chimeric mutants replacing
      neutral N-terminal residues of the HMGB2 protein with cationic sequences from
      Nhp6Ap. Surprisingly, HMGB proteins constrain DNA winding, and this torsional
      constraint is released over short timescales. These measurements reveal the
      microscopic dissociation rates of HMGB from DNA. Separate microscopic and
      macroscopic (or local and non-local) unbinding rates have been previously
      proposed, but never independently observed. Microscopic dissociation rates for
      the chimeric mutants (~10 s(-1)) are higher than those observed for wild-type
      proteins (~0.1-1.0 s(-1)), reflecting their reduced ability to bend DNA through
      short-range interactions, despite their increased DNA-binding affinity.
      Therefore, transient local HMGB-DNA contacts dominate the DNA-bending mechanism
      used by these important architectural proteins to increase DNA flexibility.

PMID- 23143112
TI  - Scrotal pearls and pitfalls: ultrasound findings of benign scrotal lesions.
AB  - Scrotal symptoms including palpable mass or pain often bring men to medical
      attention. Ultrasound serves as an extension of the physical examination in these
      patients and, in most cases, allows definitive diagnosis. Although the diagnosis
      of malignancy is of greatest concern both to the patient and clinician, a number
      of benign scrotal pathologies exist and most have characteristic imaging
      features. Knowledge of these imaging findings can help the radiologist to
      confidently identify common benign scrotal conditions. Location and imaging
      characteristics of uncommon lesions help to establish a rational differential
      diagnosis and appropriate recommendations for patient management.

PMID- 23143113
TI  - Religious faith and psychosocial adaptation among stroke patients in Kuwait: a
      mixed method study.
AB  - Religious faith is central to life for Muslim patients in Kuwait, so it may
      influence adaptation and rehabilitation. This study explored quantitative
      associations among religious faith, self-efficacy, and life satisfaction in 40
      female stroke patients and explored the influence of religion within stroke
      rehabilitation through qualitative interviews with 12 health professionals. The
      quantitative measure of religious faith did not relate to life satisfaction or
      self-efficacy in stroke patients. However, the health professionals described
      religious coping as influencing adaptation post-stroke. Fatalistic beliefs were
      thought to have mixed influences on rehabilitation. Measuring religious faith
      among Muslims through a standardized scale is debated. The qualitative accounts
      suggest that religious beliefs need to be acknowledged in stroke rehabilitation
      in Kuwait. 

PMID- 23143114
TI  - Sense of coherence, food selection and leisure time physical activity in type 1
      diabetes.
AB  - BACKGROUND: Successful management of type 1 diabetes depends on the self-care
      practices. Sense of coherence has been associated with various measures of
      lifestyle choices. We aimed to study the associations between sense of coherence
      and self-care practices in patients with type 1 diabetes. We hypothesized that
      patients with weak sense of coherence have less prudent food choices and lower
      physical activity. METHODS: Cross-sectional data from 1104 patients (44% men,
      mean age 45+/-12 years) from the FinnDiane Study were available. Sense of
      coherence, dietary intake, and leisure time physical activity were evaluated
      using self-reported questionnaires. Diet score was calculated based on the degree
      to which food choices complied with dietary guidelines. Weekly metabolic
      equivalent hours were calculated by multiplying the activity duration by the
      activity- and intensity-specific metabolic equivalent. RESULTS: The sense of
      coherence score correlated positively both with the diet score and the weekly
      metabolic equivalent hours. Those in the lowest sense of coherence tertile had
      both the lowest diet scores and the lowest weekly metabolic equivalent hours
      values. Among women, the sense of coherence score was associated with the diet
      score when adjusted for age, socioeconomic status, received dietary guidance, and
      nephropathy status. The sense of coherence score independently predicted the
      metabolic equivalent hours value in men. CONCLUSIONS: A higher sense of coherence
      score predicted more prudent food choices in women and higher physical activity
      in men. In the future, the health consequences associated with a weak sense of
      coherence should be studied prospectively. Also, the possibility to use the sense
      of coherence questionnaire as a screening instrument to identify patients who
      could benefit from intensified counseling should be investigated.

PMID- 23143117
TI  - [Ketamine for treatment of therapy-resistant depression: a case study].

PMID- 23143118
TI  - [Management of dysphagic patients with acute stroke].
AB  - This article describes expert recommendations on the management of patients with
      acute stroke, who might suffer from dysphagia. The main goal is to reduce the
      risk of aspiration pneumonia (AP). Nurses or physicians should perform the
      standardized swallowing assessment (SSA) as soon as possible and speech-language
      therapists have to perform examinations comprising assessment of predictors for
      aspiration and for AP as well as the clinical swallowing assessment. Dependent on
      the results, flexible endoscopic or video fluoroscopic evaluation of swallowing
      has to be performed so that indications for enteral or oral feeding can be made.
      Furthermore, the risk of AP can be minimized. This article presents algorithms
      which enable decision-making with regard to diagnostic and therapeutic measures.

PMID- 23143119
TI  - HBV-related events after allogeneic hematopoetic stem cell transplantation in a
      center from Turkey.
AB  - To investigate the frequency of hepatitis B virus (HBV)-related events after
      allogeneic HCT in a moderate endemic area for HBV infection. The data of 197
      patients who underwent allogeneic hematopoetic stem cell transplatation (HCT)
      from September 2003 through December 2010 were reviewed retrospectively with
      respect to HBV-related events. Resolved HBV infection was described as negative
      HBsAg, positive HBcAb, and positive HBsAb. Latent HBV infection was defined in
      patients with HBcAb positivity in the abscence of HBV DNA and HBsAb. Hepatitis B
      naive patients are defined as the patiens with no serological or molecular marker
      related to HBV. Seropositive patients were the patients with positive HBsAg and
      HBV-DNA. Median age was 28 (range, 15-64) years, with 128 male and 69 female
      patients. Median follow-up of the cohort was 8 (range, 0.5-78) months. We
      detected HBV-related events in 7 (3.6 %) recipients after allogeneic HCT. Five
      (71.4 %) of these events were HBV reactivation, while two cases (28.6 %) had
      acute hepatitis B infection. Four of the five reactivations were in the
      seropositive group (80 %), while one ocurred in a patient with resolved
      hepatitis. Two patients who developed acute hepatitis B were HBV naive and
      previously immunized patients, respectively. Hepatitis B virus reactivation
      remains a problem in seropositive patients and might require more effective
      treatment strategies.

PMID- 23143120
TI  - Transcatheter aortic valve implantation: revolution and evolution 10 years on.

PMID- 23143121
TI  - The art of assessing aortic stenosis.
AB  - This review describes the assessment of the aortic valve by echocardiography and
      also the roles that multidetector CT (MDCT) and cardiac magnetic resonance have
      to play as complimentary imaging modalities. It describes how to resolve apparent
      discrepancies in grading aortic stenosis and discusses the management of
      apparently moderate stenosis associated with cardiac symptoms or left ventricular
      dysfunction. The role of cardiac imaging including three-dimensional (3D)
      echocardiography and MDCT scanning in the preparation for transcatheter aortic
      valve implantation and during and after the procedure are described. While
      echocardiography remains the mainstay of imaging, 3D modalities, notably MDCT,
      are increasingly useful and a multimodality approach is likely to become
      established as routine clinical practice.

PMID- 23143122
TI  - Contemporary management of aortic stenosis: surgical aortic valve replacement
      remains the gold standard.
AB  - Aortic valve disease is the most frequent acquired heart valve lesion in humans.
      In western communities, approximately 90% of patients present with aortic
      stenosis (AS), predominantly of a calcific degenerative aetiology. The remaining
      approximately 10% of patients predominantly present with aortic valve
      incompetence.

PMID- 23143123
TI  - TAVI: from home-made prosthesis to global interventional phenomenon.
AB  - Surgical aortic valve replacement (AVR) was first developed in the 1960s. The
      procedure rapidly became first-line therapy for the management of symptomatic
      severe aortic stenosis (AS). Concurrently, percutaneous catheter-mounted valves
      were evaluated in animals, although these did not make it into clinical use. In
      the 1980s, balloon aortic valvuloplasty appeared as an alternative to AVR.
      However, despite short-term symptomatic relief and improved haemodynamics,
      valvuloplasty did not change the natural course of the disease. Collapsible metal
      scaffolds with biological valves for permanent implantation were investigated in
      animal models in the early 1990s. In 2002, the first-in-human transcatheter
      aortic valve implantation (TAVI) was performed via an antegrade, transvenous
      approach. Later, the retrograde approach, with access via the femoral artery,
      gained favour and became a reproducible, fully percutaneous procedure. Recently,
      subclavian access has also proven to be a feasible and reproducible alternative.
      Both the antegrade transapical and retrograde direct aortic approaches now offer
      alternatives for patients with unsuitable vascular access via the femoral route.
      Within a decade, TAVI spread throughout the world, became approved by regulatory
      authorities, and is now part of the armamentarium in the treatment of AS as a
      lifesaving, but less invasive, procedure.

PMID- 23143124
TI  - Transatlantic perspectives on TAVI: from essential infrastructure and integration
      to expansion, research and development.

PMID- 23143125
TI  - Transcatheter aortic valve implantation: the procedure.
AB  - Transcatheter aortic valve implantation (TAVI) for the treatment of symptomatic
      severe aortic stenosis has emerged as an effective treatment for high risk
      patients. In 2002 TAVI was performed for the first time in a human by Alain
      Cribier, using an antegrade access approach via the femoral vein, crossing the
      intra-atrial septum after puncture and passing the native aortic valve in the
      direction of blood flow. This technically demanding approach was subsequently
      replaced by retrograde transfemoral arterial access. For patients with severe
      peripheral vascular disease or inadequately sized femoral arteries, the
      transapical route provides an alternative route with antegrade access to the
      aortic valve via puncture of the anterolateral wall of the left ventricle. The
      transsubclavian access approach using most frequently the left subclavian artery
      and direct transaortic access have been introduced more recently and attest to
      the versatility of TAVI in terms of access site. This article will focus on the
      different access site options available to operators, provide a step-by-step
      guide through the procedure, and a detailed description of the technological
      evolution of transcatheter heart valve systems.

PMID- 23143126
TI  - Transcatheter aortic valve implantation: prevention and management of
      complications.
AB  - Assessment of elderly patients with severe aortic stenosis and decisions in terms
      of management strategy (conservative with or without balloon aortic
      valvuloplasty, transcatheter aortic valve implantation (TAVI) or surgical aortic
      valve replacement) are complex and warrant a multidisciplinary approach involving
      collaboration between experienced cardiac surgeons, interventional cardiologists,
      cardiac imaging specialists, anaesthesiologists, geriatricians and a specialised
      nursing staff. Patient history, comorbid conditions, perioperative risk
      stratification as well as anatomical and procedural considerations require
      careful review on an individual, case-by-case basis and have a major impact on
      treatment allocation. The aims of this article are to provide insights into the
      fundamental role of appropriate patient screening and selection, and to review
      the nature, management and prevention of the most important procedural
      complications associated with the TAVI procedure.

PMID- 23143127
TI  - Transcatheter aortic valve implantation: the evidence.
AB  - Transcatheter aortic valve implantation (TAVI) is the new standard-of-care for
      inoperable patients with better outcome than conservative management, including
      balloon valvuloplasty only. In high-risk patients, TAVI has clearly shown non
      inferiority compared with surgical aortic valve replacement. Although data from
      national multicentre registries are very encouraging and we are already
      speculating about the use of TAVI in intermediate-risk patients, it is of note
      that the two commercially available and used transcatheter heart valves (THVs)
      have not yet been assessed by randomised clinical trials in those patients.
      Technological advances promise to simplify TAVI and to improve outcome by
      reducing the rate of TAVI-specific issues such as stroke, peri-prosthetic aortic
      regurgitation, acute kidney injury, vascular complications and conduction
      disturbances. Therefore, results from ongoing trials with the available THVs are
      urgently awaited. In future trials, screening, treatment and follow-up of TAVI
      patients will need to follow a standardised protocol to achieve better
      comparability of study data to address, decisively, the question of whether
      intermediate-risk or low-risk patients may also profit from a less invasive TAVI
      approach.

PMID- 23143128
TI  - Degenerative calcific aortic stenosis: a natural history.
AB  - Aortic stenosis (AS) is the consequence of active valve remodelling, which can be
      easily diagnosed, but for which no preventive strategy is available. It is the
      most common valve disease in Western countries, where its prevalence increases
      with age, reaching about 3% after the age of 75. The burden of AS is high and is
      expected to double within the next 50 years. Surgery is recommended in patients
      with severe symptomatic AS. In practice, however, surgery is often denied to the
      elderly owing to extensive comorbidities or 'frailty' and, as a consequence,
      decision-making is not always consistent with risk-benefit analysis. These
      findings highlight the need for less invasive approaches in high-risk patients
      and account for the rapid development of transcatheter aortic valve implantation
      (TAVI). Preliminary analyses suggest that in-hospital costs of TAVI compare
      favourably with the costs of surgery. Cost-effectiveness analyses are needed but
      should be interpreted with caution, given the discrepancies in analyses
      concerning surgery.

PMID- 23143129
TI  - Transcatheter aortic valve implantation: changing patient populations and novel
      indications.

PMID- 23143130
TI  - Views on the diagnostic labels of autism and Asperger's disorder and the proposed
      changes in the DSM.
AB  - With the approaching release of the DSM V in 2013, there has been much debate
      about the proposal to remove the diagnostic label of Asperger's disorder from the
      new DSM. This study explored how health and education professionals perceive the
      conditions of autism and Asperger's disorder and their views on the proposed
      diagnostic changes. Analysis of the 547 participant responses confirmed an
      increase stigma is associated with the label of autism, with autism considered to
      be a more severe than the condition of Asperger's disorder. Approximately half of
      the participants reported being opposed to proposed diagnostic changes and of the
      remaining participants, 22% supported the proposed changes and 28% expressed
      uncertainty.

PMID- 23143131
TI  - Standardizing ADOS domain scores: separating severity of social affect and
      restricted and repetitive behaviors.
AB  - Standardized Autism Diagnostic Observation Schedule (ADOS) scores provide a
      measure of autism severity that is less influenced by child characteristics than
      raw totals (Gotham et al. in Journal of Autism and Developmental Disorders,
      39(5), 693-705 2009). However, these scores combine symptoms from the Social
      Affect (SA) and Restricted and Repetitive Behaviors (RRB) domains. Separate
      calibrations of each domain would provide a clearer picture of ASD dimensions.
      The current study separately calibrated raw totals from the ADOS SA and RRB
      domains. Standardized domain scores were less influenced by child characteristics
      than raw domain totals, thereby increasing their utility as indicators of Social
      Communication and Repetitive Behavior severity. Calibrated domain scores should
      facilitate efforts to examine trajectories of ASD symptoms and links between
      neurobiological and behavioral dimensions. 

PMID- 23143132
TI  - Recurrence rate of Morgagni diaphragmatic hernia following laparoscopic repair.
AB  - PURPOSE: Morgagni diaphragmatic hernia can be repaired laparoscopically. The aim
      of this study is to evaluate the outcome of this minimally invasive approach.
      METHODS: A retrospective review was conducted on all consecutive children who
      underwent repair of Morgagni hernia from January 2002 to December 2011 in our
      hospital. Data are expressed as median (range). RESULTS: There were 12 children
      with Morgagni hernia. Age at surgery was 7.5 months (2-125). Associated
      malformations were present in 7 children (58 %). All children underwent initial
      laparoscopic approach. Two children (16 %) underwent conversion to open surgery.
      The hernia was closed primarily in 11 children (92 %), using a polyester patch in
      1 (8 %). There were no intraoperative or immediate postoperative complications.
      Five children (42 %), all repaired initially without a patch, had a recurrence of
      the Morgagni hernia. The repair of the recurrent hernia was performed
      laparoscopically in four out of the five children, and a patch was used in two
      patients with no further recurrences or complications. CONCLUSIONS: There is a
      high rate of recurrence after laparoscopic Morgagni hernia repair. This is
      exclusively associated with laparoscopic repair without patch, and it is in
      contrast with the low recurrence rate reported previously. More frequent use of
      patch may be beneficial.

PMID- 23143133
TI  - Rebuild, restore, reinnervate: do human tissue engineered dermo-epidermal skin
      analogs attract host nerve fibers for innervation?
AB  - PURPOSE: Tissue engineered skin substitutes are a promising tool to cover large
      skin defects, but little is known about reinnervation of transplants. In this
      experimental study, we analyzed the ingrowth of host peripheral nerve fibers into
      human tissue engineered dermo-epidermal skin substitutes in a rat model. Using
      varying cell types in the epidermal compartment, we wanted to assess the
      influence of epidermal cell types on reinnervation of the substitute. METHODS: We
      isolated keratinocytes, melanocytes, fibroblasts, and eccrine sweat gland cells
      from human skin biopsies. After expansion, epidermal cells were seeded on human
      dermal fibroblast-containing collagen type I hydrogels as follows: (1)
      keratinocytes only, (2) keratinocytes with melanocytes, (3) sweat gland cells.
      These substitutes were transplanted into full-thickness skin wounds on the back
      of immuno-incompetent rats and were analyzed after 3 and 8 weeks. Histological
      sections were examined with regard to myelinated and unmyelinated nerve fiber
      ingrowth using markers such as PGP9.5, NF-200, and NF-145. RESULTS: After 3
      weeks, the skin substitutes of all three epidermal cell variants showed no
      neuronal ingrowth from the host into the transplant. After 8 weeks, we could
      detect an innervation of all three types of skin substitutes. However, the nerve
      fibers were restricted to the dermal compartment and we could not find any
      unmyelinated fibers in the epidermis. Furthermore, there was no distinct
      difference between the constructs resulting from the different cell types used to
      generate an epidermis. CONCLUSION: Our human tissue engineered dermo-epidermal
      skin substitutes demonstrate a host-derived innervation of the dermal compartment
      as early as 8 weeks after transplantation. Thus, our substitutes apparently have
      the capacity to attract nerve fibers from adjacent host tissues, which also grow
      into grafts and thereby potentially restore skin sensitivity.

PMID- 23143134
TI  - Laparoscopy-assisted surgery for neonatal intestinal atresia and stenosis: a
      report of 35 cases.
AB  - PURPOSE: Jejunal-ileal atresias are the most common causes of intestinal
      occlusion in neonatal period. Treatment is classically performed by a right upper
      quadrant transverse laparotomy. Our study aimed to present our initial experience
      of intestinal atresia in newborn treated with laparoscopic assisted approach.
      METHODS: Overall 35 small intestinal atresias, which occurred in infants from
      September 2009 to July 2012 in our hospital, were treated by laparoscopy-assisted
      procedure. After carefully inspecting through laparoscope by a multi-port or
      single-site approach, these were definitely diagnosed. The anastomosis of
      intestinal atresia was manually performed after exteriorization of the bowel via
      the umbilical port site incision. RESULTS: There were no conversions to an open
      procedure and no intraoperative various complications. The incision of umbilical
      port was about 2-2.5 cm. The post-operative course was uneventful. CONCLUSION:
      Laparoscopy-assisted procedure could be safely accomplished in neonates with
      intestinal atresia. Comparing to open surgery, parents were extremely satisfied
      with the cosmetic results. The early experience suggests that the outcomes are
      excellent.

PMID- 23143135
TI  - Tobacco retail clustering around schools in New York City: examining "place" and
      "space".
AB  - This paper investigates whether tobacco retailers cluster around schools in New
      York City. Retail clustering is assessed through two measures: (1) proximity of
      retailers to schools and (2) density of retailers around schools. Through
      exploratory spatial statistics and OLS regression, we analyze how retailer
      density and proximity to schools vary in relation to socio-demographic
      differences across NYC community districts. As a secondary objective, we test
      whether patterns of retail clustering differ when assessed by proximity versus
      density. We identify areas of positive spatial autocorrelation in lower Manhattan
      and the Bronx, indicating that some NYC community districts have significantly
      higher density of tobacco retailers around schools than others. The density and
      proximity of tobacco retailers to schools co-vary with population density,
      commercial land use and broad indicators of social disadvantage including health
      insurance coverage. We also find that patterns of retail clustering differ when
      assessed using either density or proximity, suggesting that land use
      interventions that restrict tobacco retail proximity to schools might not address
      retailer density around schools.

PMID- 23143136
TI  - The impact of nursing homes on small-area life expectancies.
AB  - The geographical distribution of nursing homes can significantly distort small
      area life expectancy estimations. Consequently, uncorrected life expectancies
      should not be used for small-area life expectancy comparisons. Instead, several
      nursing home corrections have been proposed. The practical use of these
      corrections, however, is severely limited by data availability. This paper
      introduces a new, model-based nursing home correction that requires considerably
      less detailed nursing home data. A formal comparison shows that the proposed
      model-based approach is the recommended correction for all small-area life
      expectancy estimations where detailed previous residential address information of
      the nursing home population is not available. This makes the approach highly
      relevant for a wide range of empirical applications.

PMID- 23143137
TI  - Retinal endothelial cell apoptosis.
AB  - Retinal endothelial cell (REC) apoptosis occurs in response to a number of
      stressors, including high glucose, oxidative stress, hypoxia. Because these
      stressors are common factors in a number of ocular diseases, it is critical to
      understand the cellular mechanisms by which apoptosis occurs in REC. This review
      discusses the various models of REC used in ophthalmological research. The
      mechanisms responsible for REC apoptosis are discussed, as well as potential
      therapeutics currently under development to prevent REC apoptosis. The primary
      goal of this review is provide the reader with a background knowledge of the
      current state of research ongoing in REC apoptosis and potential avenues for
      future testing.

PMID- 23143138
TI  - Sodium arsenite exposure inhibits AKT and Stat3 activation, suppresses self
      renewal and induces apoptotic death of embryonic stem cells.
AB  - Sodium arsenite exposure at concentration >5 MUM may induce embryotoxic and
      teratogenic effects in animal models. Long-term health effects of sodium arsenite
      from contaminated drinking water may result in different forms of cancer and
      neurological abnormalities. As cancer development processes seem to be originated
      in stem cells, we have chosen to examine the effects of sodium arsenite on
      signaling pathways and the corresponding transcription factors that regulate cell
      viability and self-renewal in mouse embryonic stem cells (ESC) and mouse neural
      stem/precursor cells. We demonstrated that the crucial signaling pathway, which
      was substantially suppressed by sodium arsenite exposure (4 MUM) in ESC, was the
      PI3K-AKT pathway linked with numerous downstream targets that control cell
      survival and apoptosis. Furthermore, the whole core transcription factor
      circuitry that control self-renewal of mouse ESC (Stat3-P-Tyr705, Oct4, Sox2 and
      Nanog) was strongly down-regulated by sodium arsenite (4 MUM) exposure. This was
      followed by G2/M arrest and induction of the mitochondrial apoptotic pathway that
      might be suppressed by caspase-9 and caspase-3 inhibitors. In contrast to mouse
      ESC with very low endogenous IL6, mouse neural stem/precursor cells (C17.2 clone
      immortalized by v-myc) with high endogenous production of IL6 exhibited a strong
      resistance to cytotoxic effects of sodium arsenite that could be decreased by
      inhibitory anti-IL6 antibody or Stat3 inhibition. In summary, our data
      demonstrated suppression of self-renewal and induction of apoptosis in mouse ESC
      by sodium arsenite exposure, which was further accelerated due to simultaneous
      inhibition of the protective PI3K-AKT and Stat3-dependent pathways.

PMID- 23143139
TI  - Optimizing HIV treatment.
AB  - PURPOSE OF REVIEW: There are at least seven million people eligible for
      antiretroviral treatment but not receiving it. An additional 19 million people
      will need to start treatment in the future, as their HIV disease progresses.
      Funding for Universal Access to HIV treatment has been restricted by the Global
      Financial Crisis. RECENT FINDINGS: There are three large randomized trials
      ongoing, designed to establish the efficacy of lower than approved doses of
      antiretrovirals. If successful, the results of these trials could lower costs of
      antiretrovirals and improve the safety profiles. Clinical trials evaluating
      efavirenz, atazanavir, ritonavir and stavudine are discussed. The costs of these
      and other antiretrovirals are presented. SUMMARY: The results of these trials
      could significantly lower the costs of Universal Access. Assuming 15 million
      people on antiretroviral treatment, the reduction in unit costs of tenofovir
      (TDF)/3TC/efavirenz from dose optimization of efavirenz to 400 mg once daily
      would save US$16 per person, leading to an overall saving of US$192 million per
      year. The switch from zidovudine (ZDV)/3TC/atazanavir (ATV)/r 300/100 once daily
      to dolutegravir along with ATV/r 200/50 once daily would save US$267 per person,
      leading to an overall saving of US$801 million. The combined saving in costs from
      first- and second-line treatment would therefore be US$993 million per year.

PMID- 23143140
TI  - Emerging HIV-1 drug resistance after roll-out of antiretroviral therapy in sub
      Saharan Africa.
AB  - PURPOSE OF REVIEW: This review provides an update of recent data on the
      development of HIV-1 drug resistance during treatment and its transmission in sub
      Saharan Africa after the scale-up of antiretroviral therapy (ART). RECENT
      FINDINGS: Evidence is accumulating of a rising prevalence of transmitted HIV drug
      resistance (TDR), predominantly associated with nonnucleoside reverse
      transcriptase inhibitors (NNRTIs), in east and southern Africa. Pretherapy
      resistance is associated with first-line therapy failure. Accumulation of
      resistance mutations during first-line failure can be prevented by early
      detection and timely switching to second-line ART. Important gaps in service
      delivery and programme performance, associated with resistance development,
      affect a considerable proportion of ART programmes, particularly with respect to
      inadequate supply systems and patient retention. The reduction in new HIV
      infections associated with earlier use of ART is predicted to outweigh the risk
      of increasing TDR. Future levels of TDR are estimated to be diminished by
      improving switching practices to second-line regimens. SUMMARY: TDR is on the
      rise after the recent scale-up of ART in Africa. To prevent the development and
      spread of drug resistance and sustain the effectiveness of ART programmes, there
      is a need to improve drug supply systems, patient retention and access to routine
      viral load monitoring. Enhanced resistance monitoring is warranted in Africa.

PMID- 23143141
TI  - HIV and noncommunicable diseases:  a case for health system building.
AB  - PURPOSE OF REVIEW: Many low- and middle-income countries face a double burden of
      disease from infectious diseases such as HIV/AIDS and noncommunicable diseases
      (NCDs) such as diabetes, stroke and cancers. The health systems in such countries
      are weak and are severely challenged by the weight of a double burden of disease.
      The aim of this review is to examine current calls for a coordinated global
      response to HIV and NCDs and make a case for health system building in resource
      constrained settings. RECENT FINDINGS: The main argument in favour of a
      coordinated approach is that HIV and NCDs share many similarities that make them
      ideal candidates for a coordinated approach. Therefore, there is no need to
      reinvent the wheel, as experiences with HIV programmes can be leveraged to NCD
      programmes, and vice versa. Critics, however, worry that coordinated approaches
      could among other things adversely affect the gains of HIV programmes. SUMMARY:
      Going forward, the overall benefit of a coordinated approach will be that health
      systems could be strengthened in a sustainable manner. However, such approaches
      must carefully weigh the benefits against risks to existing structures and must
      consider all the relevant stakeholders in their implementation.

PMID- 23143142
TI  - Evaluation of low-level laser therapy effectiveness on the pain and masticatory
      performance of patients with myofascial pain.
AB  - This study investigated the effect of low-level laser therapy (LLLT) on the
      masticatory performance (MP), pressure pain threshold (PPT), and pain intensity
      in patients with myofascial pain. Twenty-one subjects, with myofascial pain
      according to Research Diagnostic Criteria/temporomandibular dysfunction, were
      divided into laser group (n = 12) and placebo group (n = 9) to receive laser
      therapy (active or placebo) two times per week for 4 weeks. The measured
      variables were: (1) MP by analysis of the geometric mean diameter (GMD) of the
      chewed particles using Optocal test material, (2) PPT by a pressure algometer,
      and (3) pain intensity by the visual analog scale (VAS). Measurements of MP and
      PPT were obtained at three time points: baseline, at the end of treatment with
      low-level laser and 30 days after (follow-up). VAS was measured at the same times
      as above and weekly throughout the laser therapy. The Friedman test was used at a
      significance level of 5% for data analysis. The study was approved by the Ethics
      Committee of the Federal University of Sergipe (CAAE: 0025.0.107.000-10). A
      reduction in the GMD of crushed particles (p < 0.01) and an increase in PPT (p <
      0.05) were seen only in the laser group when comparing the baseline and end-of
      treatment values. Both groups showed a decrease in pain intensity at the end of
      treatment. LLLT promoted an improvement in MP and PPT of the masticatory muscles.

PMID- 23143143
TI  - Benzimidazolium-based synthetic chloride and calcium transporters in bacterial
      membranes.
AB  - Herein, we present the first example of a benzimidazolium-based artificial
      transmembrane chloride transporter and a synthetic calcium ionophore that can
      regulate intracellular calcium concentrations in bacteria.

PMID- 23143144
TI  - Quality of life and the venous function of the lower limb after harvest of
      autologous external iliac vein grafts: a clinical follow-up study.
AB  - PURPOSE: To investigate the quality of life and venous function of the lower
      limbs after right external iliac vein (REIV) grafting for digestive surgery.
      METHOD: The study subjects included 66 patients treated surgically for
      hepatopancreatobiliary malignancy who underwent concomitant resection with REIV
      for use as autologous grafts. Fifteen patients completed the Chronic Lower Limb
      Venous Insufficiency Questionnaire (CIVIQ), and the venous function was assessed
      using air plethysmography (APG) and duplex ultrasound in 10 patients. The
      outcomes of the 15 patients were analyzed statistically. RESULTS: Postoperative
      morbidity related to graft harvest occurred in three of the 66 patients (5 %).
      The right legs of the follow-up patients were 6 +/- 3 % larger than the left
      legs. The mean CIVIQ score was acceptably low at 27; however, moderate symptoms
      (e.g., pain upon long-time standing or walking) occurred in seven of the 15
      patients. APG revealed moderate to severe outflow obstructions that did not
      improve during long-term observation. The blood flow depicted on duplex
      ultrasonography was significantly associated with the patients' symptoms. No deep
      venous reflux was encountered, and no right leg skin changes or venous
      claudication developed. CONCLUSIONS: The symptoms occurring after REIV resection
      can be unexpectedly prolonged. These unfavorable effects must be kept in mind and
      the possible sequelae should be carefully explained to patients preoperatively.

PMID- 23143145
TI  - Clinical significance of and future perspectives for hepatic arterial infusion
      chemotherapy in patients with liver metastases from colorectal cancer.
AB  - The most common site of metastases in patients with colorectal cancer is the
      liver. Hepatic resection is considered to be the treatment of choice for liver
      metastasis from colorectal cancer; however, hepatic resection can be performed in
      only 20 or 25% of all patients. Recurrence develops in the remnant liver or other
      organs after hepatic resection in over half of all patients with liver-only
      metastasis. Hepatic arterial infusion (HAI) chemotherapy can provide relatively
      high concentrations of drugs to microscopic or macroscopic metastases in the
      liver, with less toxicity than systemic administration. Meta-analyses have shown
      HAI chemotherapy to have a significantly higher response rate than systemic
      chemotherapy and its effect on extrahepatic metastases is negligible. HAI
      chemotherapy provides much better local control of liver metastases from
      colorectal cancer than systemic chemotherapy. However, well-controlled studies
      are needed to elucidate the optimal treatment strategies for neoadjuvant and
      postoperative adjuvant chemotherapy that optimally combine HAI chemotherapy,
      molecular targeted agents, and systemic chemotherapy such as FOLFOX or FOLFIRI.

PMID- 23143146
TI  - Closing midline abdominal incisions.
AB  - BACKGROUND: The most important wound complications are surgical site infection,
      wound dehiscence and incisional hernia. Experimental and clinical evidences
      support that the development of wound complications is closely related to the
      surgical technique at wound closure. RESULTS: The suture technique monitored
      through the suture length-to-wound length ratio is of major importance for the
      development of wound complications. The risk of wound dehiscence is low with a
      high ratio. The ratio must be higher than 4; otherwise, the risk of developing an
      incisional hernia is increased four times. With a ratio higher than 4, both the
      rate of wound infection and incisional hernia are significantly lower if closure
      is done with small stitches placed 5 to 8 mm from the wound edge than with larger
      stitches placed more than 10 mm from the wound edge. CONCLUSIONS: Midline
      incisions should be closed in one layer by a continuous suture technique. A
      monofilament suture material should be used and be tied with self-locking knots.
      Excessive tension should not be placed on the suture. Wounds must always be
      closed with a suture length-to-wound length ratio higher than 4. The only way to
      ascertain this is to measure, calculate and document the ratio at every wound
      closure. A high ratio should be accomplished with many small stitches placed 5 to
      8 mm from the wound edge at very short intervals.

PMID- 23143147
TI  - Resection strategies for neuroendocrine pancreatic neoplasms.
AB  - INTRODUCTION: Due to their rarity and lack of prospective trials, the optimal
      treatment of pancreatic neuroendocrine neoplasms (PNENs) is still debated.
      Recommendations gathered by retrospective analyses of patient data should be
      based on the new classification of neuroendocrine neoplasms. METHODS: In a
      retrospective single-center study (1990 to 2012), 127 patients with PNENs were
      included. Tumor stage and type of resections were analyzed to evaluate successful
      treatment strategies. RESULTS: Seventy-nine patients (62 %) were diagnosed with
      stage I or II, 48 patients (38 %) with stage III or IV disease; 49.6 % of all
      PNENs were nonfunctional. Surgical interventions consisted of 50 enucleations, 27
      distal resections, and 2 partial duodenopancreatectomies in patients with stage I
      or II disease. Twenty-eight patients with stage III or IV disease received a
      distal resection and in 13 patients, a partial duodenopancreatectomy was carried
      out. Exploration with debulking was performed in seven patients in stages III and
      IV. Stage-dependent 10-year survival rates were 93.7 (stages I and II, n = 79)
      and 56.0 % (stages III and IV, n = 48). CONCLUSIONS: PNENs have a good prognosis
      if they are well-differentiated and resected completely. Organ-preserving
      resection does not impair the prognosis in selected cases with stage I or II. In
      case of hepatic metastasis and advanced tumor stage, surgical reduction can
      reduce symptoms and improve the survival.

PMID- 23143148
TI  - alpha-lipoic acid reduces hypertension and increases baroreflex sensitivity in
      renovascular hypertensive rats.
AB  - Renovascular hypertension has robust effects on control of blood pressure,
      including an impairment in baroreflex mechanisms, which involves oxidative
      stress. Although &#945;-lipoic acid (LA) has been described as a potent
      antioxidant, its effect on renovascular hypertension and baroreflex sensitivity
      (BRS) has not been investigated. In the present study we analyzed the effects
      caused by chronic treatment with LA on blood pressure, heart rate and baroreflex
      sensitivity (sympathetic and parasympathetic components) in renovascular
      hypertensive rats. Male Wistar rats underwent 2-Kidney-1-Clip (2K1C) or sham
      surgery and were maintained untouched for four weeks to develop hypertension.
      Four weeks post-surgery, rats were treated with LA (60 mg/kg) or saline for 14
      days orally. On the 15th day mean arterial pressure (MAP) and heart rate (HR)
      were recorded. In addition, baroreflex sensitivity test using phenylephrine (8
      &#181;g/kg, i.v.) and sodium nitroprusside (25 &#181;g/kg, i.v.) was performed.
      Chronic treatment with LA decreased blood pressure in hypertensive animals;
      however, no significant changes in baseline HR were observed. Regarding
      baroreflex, LA treatment increased the sensitivity of both the sympathetic and
      parasympathetic components. All parameters studied were not affected by treatment
      with LA in normotensive animals. Our data suggest that chronic treatment with LA
      promotes antihypertensive effect and improves baroreflex sensitivity in rats with
      renovascular hypertension.

PMID- 23143149
TI  - One-pot synthesis of 2-phenylimidazo[1,2-alpha]pyridines from acetophenone,
      [Bmim]Br(3) and 2-aminopyridine under solvent-free conditions.
AB  - One-pot synthesis of 2-phenylimidazo[1,2-&#945;]pyridines from acetophenone,
      [Bmim]Br(3) and 2-aminopyridine under solvent-free conditions in the presence of
      Na(2)CO(3), gave the corresponding 2-phenylimidazo[1,2-&#945;]pyridines in
      excellent yields ranging  from 72% to 89%.

PMID- 23143150
TI  - Endo-S-c-di-GMP analogues-polymorphism and binding studies with class I
      riboswitch.
AB  - C-di-GMP, a cyclic guanine dinucleotide, has been shown to regulate biofilm
      formation as well as virulence gene expression in a variety of bacteria.
      Analogues of  c-di-GMP have the potential to be used as chemical probes to study
      c-di-GMP signaling and could even become drug leads for the development of anti
      biofilm compounds. Herein we report the synthesis and biophysical studies of a
      series of c-di-GMP analogues, which have both phosphate and sugar moieties
      simultaneously modified (called endo-S-c-di-GMP analogues). We used computational
      methods to predict the relative orientation of the guanine nucleobases in c-di
      GMP and analogues. DOSY NMR of the endo-S-c-di-GMP series showed that the
      polymorphism of c-di-GMP can be tuned with conservative modifications to the
      phosphate and sugar moieties (conformational steering). Binding studies with Vc2
      RNA (a class I c-di-GMP riboswitch) revealed that conservative modifications to
      the phosphate and 2'-positions of c-di-GMP dramatically affected binding to class
      I riboswitch.

PMID- 23143151
TI  - Spatial control of DNA reaction networks by DNA sequence.
AB  - We have developed a set of DNA circuits that execute during gel electrophoresis
      to yield immobile, fluorescent features in the gel. The parallel execution of
      orthogonal circuits led to the simultaneous production of different fluorescent
      lines at different positions in the gel. The positions of the lines could be
      rationally manipulated by changing the mobilities of the reactants. The ability
      to program at the nanoscale so as to produce patterns at the macroscale is a step
      towards programmable, synthetic chemical systems for generating defined
      spatiotemporal patterns.

PMID- 23143152
TI  - By improving regional cortical blood flow, attenuating mitochondrial dysfunction
      and sequential apoptosis  galangin acts as a potential neuroprotective agent
      after  acute ischemic stroke.
AB  - Ischemic stroke is a devastating disease with a complex pathophysiology. Galangin
      is a natural flavonoid isolated from the rhizome of Alpina officinarum Hance,
      which has been widely used as an antioxidant agent. However, its effects against
      ischemic stroke have not been reported and its related neuroprotective mechanism
      has not  really been explored. In this study, neurological behavior, cerebral
      infarct volumes and  the improvement of the regional cortical blood flow (rCBF)
      were used to evaluate the therapeutic effect of galangin in rats impaired by
      middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia.
      Furthermore, the determination of mitochondrial function and Western blot of
      apoptosis-related proteins were performed to interpret the neuroprotective
      mechanism of galangin. The results showed that galangin alleviated the neurologic
      impairments, reduced cerebral infarct at 24 h after MCAO and exerted a protective
      effect on the mitochondria with decreased production of mitochondrial reactive
      oxygen species (ROS). These effects were consistent with improvements in the
      membrane potential level (Dym), membrane fluidity, and degree of mitochondrial
      swelling in a dose-dependent manner. Moreover, galangin significantly improved
      the reduced rCBF after MCAO. Western blot analysis revealed that galangin also
      inhibited apoptosis in a dose-dependent manner concomitant with the up-regulation
      of Bcl-2 expression, down-regulation of Bax expression and the Bax/Bcl-2 ratio, a
      reduction in cytochrome c release from the mitochondria to the cytosol, the
      reduced expression of activated caspase-3 and the cleavage of poly(ADP-ribose)
      polymerase (PARP). All these data in this study demonstrated that galangin might
      have therapeutic potential for ischemic stroke and play its protective role
      through the improvement in rCBF, mitochondrial protection and inhibiting caspase
      dependent mitochondrial cell death pathway for the first time.

PMID- 23143153
TI  - Exploring implicit and explicit aspects of sense of agency.
AB  - Sense of agency refers to the sense of initiating and controlling actions in
      order to influence events in the outside world. Recently, a distinction between
      implicit and explicit aspects of sense of agency has been proposed, analogous to
      distinctions found in other areas of cognition, notably learning. However, there
      is yet no strong evidence supporting separable implicit and explicit components
      of sense of agency. The so-called 'Perruchet paradigm' offers one of the few
      convincing demonstrations of separable implicit and explicit learning systems. We
      adopted this approach to evaluate the implicit-explicit distinction in the
      context of a simple task in which outcomes were probabilistically caused by
      actions. In line with our initial predictions, we found evidence of a
      dissociation. We discuss the implications of this result for theories of sense of
      agency.

PMID- 23143154
TI  - Cigarette smoke extract-induced adipogenesis in Graves' orbital fibroblasts is
      inhibited by quercetin via reduction in oxidative stress.
AB  - Cigarette smoking is known to aggravate Graves' orbitopathy (GO) severity by
      enhancing adipogenesis. We investigated the effect of quercetin, an antioxidant,
      on adipocyte differentiation induced by cigarette smoke extract (CSE) in primary
      cultured orbital fibroblasts (OFs) from GO patients. Freshly prepared CSE was
      added to the cells and H(2)O(2) was used as a positive control. Intracellular
      reactive oxygen species (ROS) generation and adipogenesis were measured. The
      expressions of proteins peroxisome proliferator-activated receptor (PPAR) gamma,
      CCAAT-enhancer-binding proteins (C/EBP) alpha and beta, and heme oxygenase-1 (HO
      1), an antioxidant enzyme, were examined during adipogenic differentiation. In
      result, CSE and H(2)O(2) dose-dependently stimulated intracellular ROS production
      in normal and Graves' OFs. The effect of 2% CSE was similar to that of 10 MUM
      H(2)O(2); both concentrations were noncytotoxic and were used throughout the
      experiment. Quercetin pretreatment reduced the ROS generation stimulated by
      either CSE or H(2)O(2) in preadipocyte OFs. CSE and H(2)O(2) stimulated adipocyte
      differentiation in cultured OFs. The addition of quercetin (50 or 100 MUM)
      suppressed adipogenesis. Quercetin also suppressed ROS generation in
      differentiating OFs during adipogenesis stimulated by CSE and H(2)O(2).
      Additionally, the expressions of PPARgamma, C/EBPalpha, and C/EBPbeta proteins
      were reduced in the quercetin-treated OFs. Quercetin also reduced the CSE- and
      H(2)O(2)-induced upregulation of ROS and HO-1 protein in differentiated OFs and
      preadipocyte OFs. As shown in this study, quercetin inhibited adipogenesis by
      reducing ROS in vitro, supporting the use of quercetin in the treatment of GO.

PMID- 23143155
TI  - Categorising paediatric prescribing errors by junior doctors through prescribing
      competency assessment: does assessment reflect actual practice?
AB  - PURPOSE: It is recognised that paediatric prescribing errors are prevalent, and
      that most are made by junior doctors; however, detecting errors in order to
      demonstrate actual error rates can be difficult. There is evidence to suggest
      that dosing errors are the most common type of prescribing error in practice, but
      there has been little research on whether prescribing assessments are an
      effective reflection of actual practice.This article aims to determine if
      prescribing error types in a paediatric prescribing competency assessment
      reflects error types seen in actual practice. METHODS: This study was conducted
      in Royal Manchester Children's Hospital (RMCH) and the participants were junior
      doctors working at RMCH in 2010-2011. The intervention was a prescribing
      competency assessment package at RMCH.The main outcome measurement was the
      category and rate of prescribing errors. Results were taken from the junior
      doctors' prescribing competency assessment. The assessment papers were analysed
      for errors and the errors were then broken down into pre-defined categories.
      RESULTS: Rates of prescribing errors in the competency assessment are higher than
      published results shown in practice (23.1 %). The most common type of prescribing
      error (incorrect calculation of dose) reflects results seen in actual practice.
      CONCLUSION: The types of prescribing errors made in the competency assessment are
      reflective of errors made in actual practice. Prescribing teaching can be
      tailored according to the types of errors noted; and the prescribing competency
      package as a whole can be used to educate junior doctors on good prescribing
      practice and reduce prescribing errors.

PMID- 23143156
TI  - Serial CSF sampling over a period of 30 h via an indwelling spinal catheter in
      healthy volunteers: headache, back pain, tolerability and measured acetylcholine
      profile.
AB  - BACKGROUND/AIM: Timed interval cerebrospinal fluid (CSF) sampling by indwelling
      catheterization can be a valuable corroborative tool for the pharmacokinetic and
      pharmacodynamic assessment of drugs. CSF sampling in studies on drug candidates
      for Alzheimer's disease have been conducted in evaluations of the biomarkers
      acetylcholine (ACh), tau proteins, amyloid precursor protein and beta-amyloid
      fragments. The primary aim of this study was to study the feasibility and the
      burden on the healthy volunteers of serial CSF sampling within the contract
      research organization environment in order to establish a standardized research
      tool for future drug development studies. MATERIALS AND METHODS: This study is a
      validation study in healthy subjects: eight healthy male subjects aged 55-75
      years were enrolled. After eligibility had been confirmed, the subjects were
      admitted to the clinical pharmacology unit 2 days before starting the CSF
      sampling procedure. Hydration by drip infusion of 2 L saline was performed for 24
      h before starting the CSF sampling procedure, and for antithrombotic purposes,
      Fraxiparine (nadroparine calcium) was given 12 and 36 h after intradural
      catheterization. CSF catheterization was performed by board-certified
      anesthesiologists with experience in inserting indwelling intrathecal catheters.
      Subjects only required to remain in a horizontal position for the first 24 h
      after removal of the catheter. CSF and blood samples were collected by interval
      sampling over a 30-h period. RESULTS: The study was completed by seven of the
      eight subjects. Six subjects who completed the study reported adverse effects
      (AEs) which were all mild and from which they recovered during their stay in the
      clinic. A total of 25 AEs were reported of which 13 were considered to be
      procedure-related. The procedure was well tolerated by all participating
      subjects, and the VAS scale scores for headache and back pain were low. CSF
      samples were analyzed for ACh. All values were above the lowest limit of
      quantification. On average, the ACh concentration started at a low level but rose
      between 1 and 2 h after insertion of the catheter and then remained high during
      the whole sampling period up to 30 h. CONCLUSION: Serial sampling of CSF in seven
      healthy volunteers up to 30 h occurred without serious complications and was well
      tolerated. The CSF collected was of good quality and facilitated the assessment
      of an Alzheimer's disease-sensitive biomarker. We conclude that this validation
      study can form the basis for future patient studies aimed at elucidating disease
      mechanisms and the pharmacodynamics of drugs in the developmental stage.

PMID- 23143157
TI  - [Can a splenic abscess be punctured and drained or should it be left alone?].

PMID- 23143158
TI  - Building analytic capacity, facilitating partnerships, and promoting data use in
      state health agencies: a distance-based workforce development initiative applied
      to maternal and child health epidemiology.
AB  - The purpose of this article is to summarize the methodology, partnerships, and
      products developed as a result of a distance-based workforce development
      initiative to improve analytic capacity among maternal and child health (MCH)
      epidemiologists in state health agencies. This effort was initiated by the
      Centers for Disease Control's MCH Epidemiology Program and faculty at the
      University of Illinois at Chicago to encourage and support the use of
      surveillance data by MCH epidemiologists and program staff in state agencies.
      Beginning in 2005, distance-based training in advanced analytic skills was
      provided to MCH epidemiologists. To support participants, this model of workforce
      development included: lectures about the practical application of innovative
      epidemiologic methods, development of multidisciplinary teams within and across
      agencies, and systematic, tailored technical assistance The goal of this
      initiative evolved to emphasize the direct application of advanced methods to the
      development of state data products using complex sample surveys, resulting in the
      articles published in this supplement to MCHJ. Innovative methods were applied by
      participating MCH epidemiologists, including regional analyses across geographies
      and datasets, multilevel analyses of state policies, and new indicator
      development. Support was provided for developing cross-state and regional
      partnerships and for developing and publishing the results of analytic projects.
      This collaboration was successful in building analytic capacity, facilitating
      partnerships and promoting surveillance data use to address state MCH priorities,
      and may have broader application beyond MCH epidemiology. In an era of decreasing
      resources, such partnership efforts between state and federal agencies and
      academia are essential for promoting effective data use.

PMID- 23143159
TI  - Increased risk of left heart valve regurgitation associated with benfluorex use
      in patients with diabetes mellitus: a multicenter study.
AB  - BACKGROUND: Benfluorex was withdrawn from European markets in June 2010 after
      reports of an association with heart valve lesions. The link between benfluorex
      and valve regurgitations was based on small observational studies and
      retrospective estimations. We therefore designed an echocardiography-based
      multicenter study to compare the frequency of left heart valve regurgitations in
      diabetic patients exposed to benfluorex for at least 3 months and in diabetic
      control subjects never exposed to the drug. METHODS AND RESULTS: This reader
      blinded, controlled study conducted in 10 centers in France between February 2010
      and September 2011 prospectively included 376 diabetic subjects previously
      exposed to benfluorex who were referred by primary care physicians for
      echocardiography and 376 diabetic control subjects. Through the use of propensity
      scores, 293 patients and 293 control subjects were matched for age, sex, body
      mass index, smoking, dyslipidemia, hypertension, and coronary artery disease. The
      main outcome measure was the frequency of mild or greater left heart valve
      regurgitations. In the matched sample, the frequency and relative risk (odds
      ratio) of mild or greater left heart valve regurgitations were significantly
      increased in benfluorex patients compared with control subjects: 31.0% versus
      12.9% (odds ratio, 3.55; 95% confidence interval, 2.03-6.21) for aortic and/or
      mitral regurgitation, 19.8% versus 4.7% (odds ratio, 5.29; 95% confidence
      interval, 2.46-11.4) for aortic regurgitation, and 19.4% versus 9.6% (odds ratio,
      2.38; 95% confidence interval, 1.27-4.45) for mitral regurgitation. CONCLUSIONS:
      Our results indicate that the use of benfluorex is associated with a significant
      increase in the frequency of left heart valve regurgitations in diabetic
      patients. The natural history of benfluorex-induced valve abnormalities needs
      further research.

PMID- 23143160
TI  - Study on application of optical clearing technique in skin diseases.
AB  - So far, the study of the optical clearing is almost always about healthy tissue.
      However, the ultimate goal is to detect diseases for clinical application.
      Optical clearing on diseased skins is explored. The effect is evaluated by
      applying a combined liquid paraffin and glycerol mixed solution on several kinds
      of diseased skins in vitro. Scanning experiments from optical coherence
      tomography show that it has different effects among fibroma, pigmented nevus, and
      seborrheic keratosis. Based on the results, we conclude that different skin
      diseases have different compositions and structures, and their optical parameters
      and biological characteristics should be different, which implies that the
      optical clearing technique may have selectivity and may not be suitable for all
      kinds of skin diseases.

PMID- 23143161
TI  - Using participatory approaches with older people in a residential home in Guyana:
      challenges and tensions.
AB  - Participatory approaches are a popular and entrenched strategy in community
      development, yet a number of unresolved issues and tensions persist regarding the
      definition, rationales, outcomes and ethics of participation. Despite its
      popularity there are relatively few examples of participatory projects with older
      people or in institutional settings so their potential with this group is poorly
      understood. This case study presents some of the practical and ethical challenges
      that arose over the course of a participatory project that aimed to analyse and
      improve quality of life in a residential home for older people in Guyana. Through
      a qualitative process evaluation it examines the degree of participation
      achieved, the determinants of the participatory process, the benefits the
      approach brought and the ethical dilemmas encountered. Although the degree of
      participation achieved was limited, beneficial outcomes were observed, notably
      the selection of appropriate and desirable interventions and the effect on the
      residents themselves, who valued their part in the project. The participatory
      process was unpredictable and complex, however, and key determinants of it
      included the organizational dynamics of the home and the skills, actions and
      attitudes of the researcher. Adopting a participatory approach brought valuable
      benefits in a residential home, but others adopting the approach should ensure
      they critically consider at the outset the ethical and practical dilemmas the
      setting and approach may produce and have realistic expectations of
      participation.

PMID- 23143162
TI  - Volume and outcome in rectal cancer surgery: the importance of quality
      management.
AB  - PURPOSE: For many years, the impact of the surgeon volume on short- and long-term
      outcome after rectal carcinoma surgery is controversially discussed. Literature
      and own department data were reviewed in order to clarify the impact of surgeon
      volume in the current era of total mesorectal excision surgery, multimodal
      therapy, quality management, and centralization of cancer care. METHODS: Uni- and
      multivariate analysis of data from 1,028 patients with solitary rectal carcinoma,
      treated between 1995 and 2010 at the Department of Surgery, University Hospital,
      Erlangen, Germany, was performed. Surgeons were subdivided according to the
      number of operations/year into high- (at least seven/year), medium- (three to
      six), and low- (less than three) volume surgeons. RESULTS: Of 1,028 patients, 800
      (77.8 %) were operated by five high-volume surgeons, 193 (18.8 %) by seven medium
      volume surgeons, and 35 (3.4 %) by 12 low-volume surgeons. Surgeon volume was
      significantly associated with postoperative mortality and the rate of positive
      pathological circumferential resection margin. In risk-adjusted analysis, after
      primary surgery, surgeon volume had a significant impact on observed overall
      survival and disease-free survival, but not on locoregional recurrence. After
      neoadjuvant radiochemotherapy, only observed overall survival was significantly
      influenced by surgeon volume. CONCLUSIONS: In surgical departments with special
      interest in rectal carcinoma, surgeon volume has some influence on short- and
      long-term outcome. Irrespective of this fact, specialization, experience,
      individual skill, hospital organization, and regular quality assurance are
      essential prognostic factors ensuring good results in rectal carcinoma surgery.

PMID- 23143163
TI  - Current trends in surgery for renal hyperparathyroidism (RHPT)--an international
      survey.
AB  - PURPOSE: The indications and results of preoperative localization, surgical
      strategy, indication for thymectomy, the application of intraoperative
      parathyroid hormone (PTH) monitoring, cryopreservation, and replantation of
      cryopreserved parathyroid tissue are not well documented in renal
      hyperparathyroidism (RHPT). The current trends in surgery for RHPT are to be
      evaluated in an international online survey. METHODS: Thirty-three questions
      regarding preoperative localization, surgical management of RHPT, intraoperative
      PTH monitoring, immediate/delayed autotransplantation (AT), and parathyroid
      cryopreservation were sent to members of various societies of endocrine surgeons.
      RESULTS: The data from 86 responses were analyzed, 61.6 % reported more than 50
      parathyroid surgeries per year, and 62.7 % operated on less than 16 patients with
      RHPT per year. Subtotal or total parathyroidectomy (with/without AT) was the
      standard procedure in 98.8 % of the cases. Immediate AT was performed in 40.7 %
      (72.7 % in the forearm). In most patients, the onset of graft function was
      documented later than 1 week after AT. Cryopreservation was routinely performed
      in 27.4 %. In 10.7 %, replantation was performed in more than five patients (hypo
      or aparathyroidism: n = 41; fresh graft failure: n = 13; reoperations: n = 9).
      Intraoperative PTH monitoring (in RHPT) was routinely used in 46.2 %. Its
      influence on surgical strategy was confirmed in 40 %. CONCLUSIONS: The survey
      reflects the divergent strategies applied for AT, cryopreservation, and PTH
      monitoring in RHPT.

PMID- 23143164
TI  - Transaortic aortic valve implantation: an alternative treatment option in a
      patient with lipomatosis of the heart.

PMID- 23143165
TI  - Effect of time of day and fasting duration on measures of glycaemia: analysis
      from the Whitehall II Study.
AB  - AIMS/HYPOTHESIS: We aimed to study diurnal variation in glucose regulation by
      examining the effects of time of day and fasting duration on fasting plasma
      glucose (FPG), 2 h post-load plasma glucose (2hPG) and HbA(1c) levels. METHODS:
      We analysed data from 5,978 non-diabetic white men and women from the prospective
      Whitehall II Study. All studied participants fasted for at least 8 h before a
      clinical examination, which included an OGTT and anthropometric measurements. We
      fitted mixed-effects models for FPG, 2hPG and HbA(1c) as outcome variables, and
      time of day and/or fasting duration as explanatory variables. Models were
      adjusted for age, BMI and study phase. RESULTS: Time of day and fasting duration
      were associated inversely with FPG and positively with 2hPG. The mean difference
      between measures at 08:00 and 15:00 hours in men/women was -0.46 (95% CI -0.50, 
      0.42) mmol/l/-0.39 (95% CI -0.46, -0.31) mmol/l and 1.39 (95% CI 1.25, 1.52)
      mmol/l/1.19 (95% CI 0.96, 1.42) mmol/l for FPG and 2hPG, respectively. HbA(1c)
      levels were independent of either time. Time of day and fasting duration were
      independently associated with 2hPG. In contrast, the effect of fasting duration
      on FPG was markedly attenuated with adjustment for time of day. Ageing, but not
      obesity, was associated with increased diurnal variation in glucose tolerance.
      CONCLUSIONS/INTERPRETATION: Both time of day and fasting duration should be
      considered in clinical practice and epidemiological studies, since they have
      clinically relevant effects on FPG and 2hPG levels. As biochemically expected,
      HbA(1c) levels are independent of time of blood sampling and fasting duration.

PMID- 23143166
TI  - Prediction and classification of cardiovascular disease risk in older adults with
      diabetes.
AB  - AIMS/HYPOTHESIS: We sought to derive and validate a cardiovascular disease (CVD)
      prediction algorithm for older adults with diabetes, and evaluate the incremental
      benefit of adding novel circulating biomarkers and measures of subclinical
      atherosclerosis. METHODS: As part of the Cardiovascular Health Study (CHS), a
      population-based cohort of adults aged >=65 years, we examined the 10 year risk
      of myocardial infarction, stroke and cardiovascular death in 782 older adults
      with diabetes, in whom 265 events occurred. We validated predictive models in 843
      adults with diabetes, who were followed for 7 years in a second cohort, the Multi
      Ethnic Study of Atherosclerosis (MESA); here 71 events occurred. RESULTS: The
      best fitting standard model included age, smoking, systolic blood pressure, total
      and HDL-cholesterol, creatinine and the use of glucose-lowering agents; however,
      this model had a C statistic of 0.64 and poorly classified risk in men. Novel
      biomarkers did not improve discrimination or classification. The addition of
      ankle-brachial index, electrocardiographic left ventricular hypertrophy and
      internal carotid intima-media thickness modestly improved discrimination (C
      statistic 0.68; p = 0.002) and classification (net reclassification improvement
      [NRI] 0.12; p = 0.01), mainly in those remaining free of CVD. Results were
      qualitatively similar in the MESA, with a change in C statistic from 0.65 to 0.68
      and an NRI of 0.09 upon inclusion of subclinical disease measures.
      CONCLUSIONS/INTERPRETATION: Standard clinical risk factors and novel biomarkers
      poorly discriminate and classify CVD risk in older adults with diabetes. The
      inclusion of subclinical atherosclerotic measures modestly improves these
      features, but to develop more robust risk prediction, a better understanding of
      the pathophysiology and determinants of CVD in this patient group is needed.

PMID- 23143167
TI  - Margin-negative limited resection of metastatic pancreatic tumors from rectal
      cancer preoperatively diagnosed by endoscopic ultrasound-guided fine-needle
      aspiration biopsies: report of two cases.
AB  - Pancreatic tumor metastasis from colorectal cancer is very rare. This study
      evaluated the significance of an endoscopic ultrasound-guided fine-needle
      aspiration biopsy (EUS-FNAB) and surgical treatment. Case 1 was a 67-year-old
      male with a history of rectal cancer (6 years ago) and lung metastases (5 years
      ago) who had two masses in the pancreatic head and body. Case 2 was a 58-year-old
      male with the history of rectal cancer and simultaneous lung metastasis (7 years
      ago) who had a mass in the pancreatic body. Imaging studies showed stenosis of
      the pancreatic duct with distal dilatation in both cases, mimicking primary
      pancreatic cancer. An EUS-FNAB with immunohistochemical staining made a
      definitive diagnosis of pancreatic metastasis from rectal cancer. Both patients
      received margin-negative limited resection, middle-segment-preserving
      pancreatectomy and distal pancreatectomy, respectively, and were alive 16 and 6
      months after pancreatectomy, respectively. An EUS-FNAB is helpful to make a
      definitive diagnosis of pancreatic metastasis and in determining the subsequent
      therapeutic approach.

PMID- 23143168
TI  - Outcome of surgery for ileojejunal neuroendocrine tumors.
AB  - PURPOSE: Neuroendocrine tumors (NET) of the ileum/jejunum are rare and may
      require different treatment options to provide long-term survival. The purpose of
      the study was to evaluate the outcome of surgery for ileojejunal NET. METHODS: A
      database of patients that underwent surgery for ileojejunal NETs between 1999 and
      2010 was retrospectively analyzed regarding the clinical characteristics,
      surgical therapy, survival and prognostic factors. RESULTS: Only six of 97
      patients with ileojejunal NET who underwent surgery had localized tumors (stage
      I/II), 29 had lymph node involvement (stage III) and 62 had distant metastases
      (stage IV) at the initial presentation. All stage I/II tumors were cured, in
      comparison to 69% of stage III and 0% of stage IV tumors (p = 0.01). Palliative
      surgery in combination with sequential multimodal treatment regimens resulted in
      a 5-year survival rate of 63% in patients with stage IV tumors. A multivariate
      analysis showed that incomplete resection (HR 2.87; CI 1.18-6.98; p = 0.04) and
      distant metastases (HR 5.39; 95% CI 1.23-23.57; p = 0.02) were associated with
      worse disease-specific survival. CONCLUSIONS: Localized and regionally restricted
      ileojejunal NETs have an excellent prognosis after surgical treatment. Although
      stage IV tumors cannot be cured, an aggressive surgical approach in combination
      with medical or interventional treatment can provide long-term survival.

PMID- 23143169
TI  - Efficacy of PET-CT for predicting the malignant potential of gastrointestinal
      stromal tumors.
AB  - PURPOSES: Gastrointestinal stromal tumor (GIST) is the most common sarcoma of the
      intestinal tract. The risk category is usually determined by tumor size and
      mitotic count, but accurate preoperative diagnosis of GIST is very difficult. The
      purpose of this study is to evaluate the efficacy of positron emission tomography
      (PET)-CT for predicting the malignant potential of gastrointestinal stromal
      tumors. METHODS: Ten patients with GIST who underwent a preoperative PET-CT
      examination were divided into two groups by risk category, and various factors
      were compared between the two groups. The relationships between the maximum
      standardized uptake value (SUVmax) and GIST parameters were examined. RESULTS:
      Patients were classified into two groups by their risk category:
      (low/intermediate-risk or high-risk). The SUVmax was significantly higher in the
      high-risk group (11.0 +/- 3.04) than in the low/intermediate-risk group (2.1 +/-
      1.5). The Ki67 labeling index was also significantly higher in the high-risk
      group (8.63 +/- 6.2) than in the low/intermediate-risk group (1.75 +/- 0.52).
      There was a significant correlation between the Ki67 labeling index and the
      SUVmax (p = 0.028) and between the mitotic index and the SUVmax (p = 0.029).
      CONCLUSIONS: PET-CT can predict malignant potential. Cases with a SUVmax of over
      5 may have malignant potential.

PMID- 23143170
TI  - Translation and validation of the Japanese version of the fecal incontinence
      quality of life scale.
AB  - PURPOSE: The aim of the study was to conduct a psychometric evaluation of the
      fecal incontinence quality of life scale (FIQL) in the Japanese language using
      rigorous methodologies. METHODS: The FIQL was translated into Japanese. After
      being linguistically validated, the Japanese version of the FIQL was administered
      to a sample of 119 patients who completed the questionnaire at baseline and again
      after 2 weeks. The patients filled out a general questionnaire regarding health
      (the Short-Forum 36 Health Survey), and the severity of incontinence was assessed
      at baseline (Wexner scale). RESULTS: Internal consistency was good/excellent for
      all scales (Cronbach's alpha >0.70, between 0.72 and 0.94). Stability over time
      was good for all scales (Intra-class correlation >0.80, between 0.86 and 0.93).
      The four scales of the FIQL were significantly correlated with the scales of the
      generic questionnaire on health (P < 0.0001) and the Wexner scale (P < 0.0001).
      The mean FIQL score improved significantly after treatment in the 22 patients
      whose Wexner scale scores decreased >4 points, thus indicating good sensitivity
      in all four scales and the total scale. CONCLUSIONS: The linguistic and
      psychometric evaluation demonstrated the validity of the Japanese version of the
      FIQL.

PMID- 23143171
TI  - Hand-assisted laparoscopic splenectomy for thrombocytopenia in patients with
      cirrhosis.
AB  - PURPOSE: Although splenectomy plays an important role in the management of
      patients with liver cirrhosis, the optimal technique, open surgery, total
      laparoscopic surgery or hand-assisted laparoscopic surgery (HALS), has not yet
      been defined. The present study evaluated the outcomes of HALS splenectomy for
      cirrhotic patients. METHODS: A total of 28 consecutive patients with cirrhosis
      that underwent HALS splenectomy were enrolled into this study. The preoperative
      laboratory and morphometric data, intraoperative variables and postoperative
      outcomes were reviewed from the hospital charts. RESULTS: The postoperative
      platelet count was remarkably elevated in all cases. A re-operation was required
      in 1 patient complicated with postoperative hemorrhage. Enhanced CT on POD 7
      revealed a high incidence of portal or splenic vein thrombosis (PSVT; 22
      patients, 78.6 %). PSVT was significantly associated with higher serum bilirubin,
      higher indocyanine green retention value at 15 min (ICG R-15), and larger splenic
      vein diameter. CONCLUSION: HALS splenectomy was a very feasible and appropriate
      procedure for cirrhotic patients with hypersplenism. PSVT was a frequent
      complication and large splenic vein diameter, high serum bilirubin, and high ICG
      R-15 were found to be significant risk factors for PSVT after HALS splenectomy in
      cirrhotic patients.

PMID- 23143172
TI  - Identification of a novel fosfomycin-resistant UDP-N-acetylglucosamine
      enolpyruvyl transferase (MurA) from a soil metagenome.
AB  - A soil metagenomic library was constructed and screened for clones that conferred
      fosfomycin resistance. A novel protein with 46 % identity to UDP-N
      acetylglucosamine enolpyruvyl transferase (MurA) from Desulfuromonas acetoxidans
      DSM 684 (GenBank accession number: ZP_01311756) was identified. Multiple sequence
      alignment revealed that the novel protein was a natural MurA, in which an
      aspartic acid instead of a cysteine was located in the active site. An Asp120Cys
      mutant of Escherichia coli was constructed from the subclone through site
      specific mutagenesis, and minimum inhibitory concentration of fosfomycin for the
      resistant subclone and its mutant were determined. These results showed that
      fosfomycin resistance was a result of the aspartic acid in the active site.
      Analysis of all existing MurA sequences revealed that MurAs with an active site
      aspartic acid that can confer fosfomycin resistance occur in ~14 % of bacteria.

PMID- 23143173
TI  - Cell-type-dependent enzymatic hydrolysis of palm residues: chemical and surface
      characterization of fibers and parenchyma cells.
AB  - Chemical and surface characteristics of sulfite-pretreated royal palm sheath
      (RPS) fibers and parenchyma cells were investigated in order to study cell-type
      dependent biomass hydrolysis by cellulase. Size, chemical composition, cellulose
      crystallinity and the exposure of cellulose microfibrils in pretreated RPS
      biomass affected the enzymatic accessibility and digestibility of different cell
      type substrates.

PMID- 23143174
TI  - BMP-2, VEGF and bFGF synergistically promote the osteogenic differentiation of
      rat bone marrow-derived mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) were treated with bone morphogenetic protein-2 (BMP
      2), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor
      (bFGF) dose-dependently and time-dependently. Together they caused a strong
      synergistic effect on the osteogenic differentiation of MSCs, with lower
      concentrations of each factor being enough to show the synergistic promotion (50
      ng BMP-2/ml, 1 ng VEGF/ml and 10 ng bFGF/ml). When both VEGF and bFGF were added
      in the early proliferating stage (the first 7 days) and BMP-2 was added in the
      late differentiation stage (the last 7 days), osteogenic differentiation of MSCs
      could be enhanced more effectively.

PMID- 23143175
TI  - Quantitative evaluation of Candia antarctica lipase B displayed on the cell
      surface of a Pichia pastoris based on an FS anchor system.
AB  - A new approach is described to quantify the number of enzyme molecules, such as
      Candia antarctica lipase B, that are displayed on the cell surface of Pichia
      pastoris. Enhanced green fluorescent protein (EGFP) and Candida antarctica lipase
      B (CALB) were fused and displayed on the surface of P. pastoris by linking to the
      anchor flocculation functional domain of FLO1p from Saccharomyces cerevisiae.
      Confocal laser scanning microscopy, flow cytometry, and fluorescence
      spectrophotometry were used to monitor the fluorescence intensity of fused EGFP.
      Combined with the corresponding protein concentration detected in the medium, a
      standard curve describing the relationship between the fusion protein
      concentration and fluorescence intensity were obtained and could be used to
      number CALB displayed on the cell surface. The results showed that approx. 10(4)
      molecules of CALB molecules were immobilized on the single P. pastoris cell wall
      based on FS anchor system.

PMID- 23143176
TI  - Purification and visualization of encephalomyocarditisvirus synthesized by an in
      vitro protein expression system derived from mammalian cell extract.
AB  - Virus particles are promising vehicles and templates for vaccination, drug
      delivery and material sciences. Although infectious picornaviruses can be
      synthesized from genomic or synthetic RNA by cell-free protein expression systems
      derived from mammalian cell extract, there has been no direct evidence that
      authentic viral particles are indeed synthesized in the absence of living cells.
      We purified encephalomyocarditis virus (EMCV) synthesized by a HeLa cell extract
      derived, cell-free protein expression system, and visualized the viral particles
      by transmission electron-microscopy. The in vitro-synthesized EMCV particles were
      indistinguishable from the in vivo-synthesized particles. Our results validate
      the use of the cell-free technique for the synthesis of EMCV particles.

PMID- 23143177
TI  - New strategy for specific activation of recombinant microbial pro
      transglutaminase by introducing an enterokinase cleavage site.
AB  - Recombinant microbial transglutaminase (rMTG) is usually expressed as a soluble
      zymogen (pro-rMTG) in heterologous expression systems but proteolytic activation
      of the inactive pro-rMTG is essential. Instead of screening proteases for
      activating pro-rMTG, we examined an alternative method by introducing a specific
      cleavage site of enterokinase between the pro-peptide and mature rMTG, generating
      three pro-rMTG variants (Pro-mrMTG, Pro-m-rMTG and mPro-rMTG). Pro-mrMTG and Pro
      m-rMTG were activated by enterokinase without degrading mature rMTG. The
      activation productivity of Pro-m-rMTG by enterokinase reached 92 % after 22 h
      activation, while the activation productivity of Pro-rMTG activated by trypsin
      was 47 %. MALDI-MS analysis revealed that the pro-peptide including the cleavage
      site was specifically removed from Pro-m-rMTG after activation. This methodology
      has the potential to be applied in rMTG production by incorporating highly
      specific cleavage sites of other proteases.

PMID- 23143178
TI  - Enhanced in vitro translation at reduced temperatures using a cold-shock RNA
      motif.
AB  - Cell-free synthesis of recombinant proteins has emerged as an alternative method
      of protein production although protein yields still cannot compete with in vivo
      expression techniques. In systems based on S30 extracts of Escherichia coli
      unfavorable side-reactions are involved in limiting protein yields. Therefore,
      carrying out cell-free reactions at lower temperatures might be beneficial as
      side reactions should be decreased. In this study we show that by using the 5'
      untranslated region of the cold-shock gene cspA from E. coli as mRNA leader in
      cell-free reactions, the expression temperature can be decreased and
      simultaneously leads to an increase in protein yields. A compensation for the
      lower activity of T7 RNA polymerase at lower temperatures enhances protein
      synthesis even further. Additionally, this 5'-untranslated region also
      standardizes the optimal expression temperature of different proteins.

PMID- 23143179
TI  - Intracranial artery velocity measurement using 4D PC MRI at 3 T: comparison with
      transcranial ultrasound techniques and 2D PC MRI.
AB  - INTRODUCTION: 4D phase contrast MR imaging (4D PC MRI) has been introduced for
      spatiotemporal evaluation of intracranial hemodynamics in various cerebrovascular
      diseases. However, it still lacks validation with standards of reference. Our
      goal was to compare blood flow quantification derived from 4D PC MRI with
      transcranial ultrasound and 2D PC MRI. METHODS: Velocity measurements within
      large intracranial arteries [internal carotid artery (ICA), basilar artery (BA),
      and middle cerebral artery (MCA)] were obtained in 20 young healthy volunteers
      with 4D and 2D PC MRI, transcranial Doppler sonography (TCD), and transcranial
      color-coded duplex sonography (TCCD). Maximum velocities at peak systole (PSV)
      and end diastole (EDV) were compared using regression analysis and Bland-Altman
      plots. RESULTS: Correlation of 4D PC MRI measured velocities was higher in
      comparison with TCD (r = 0.49-0.66) than with TCCD (0.35-0.44) and 2D PC MRI
      (0.52-0.60). In mid-BA and ICA C7 segment, a significant correlation was found
      with TCD (0.68-0.81 and 0.65-0.71, respectively). No significant correlation was
      found in carotid siphon. On average over all volunteers, PSVs and EDVs in MCA
      were minimally underestimated compared with TCD/TCCD. Minimal overestimation of
      velocities was found compared to TCD in mid-BA and ICA C7 segment. CONCLUSION: 4D
      PC MRI appears as valid alternative for intracranial velocity measurement
      consistent with previous reference standards, foremost with TCD. Spatiotemporal
      averaging effects might contribute to vessel size-dependent mild underestimation
      of velocities in smaller (MCA), and overestimation in larger-sized (BA and ICA)
      arteries, respectively. Complete spatiotemporal flow analysis may be advantageous
      in anatomically complex regions (e.g. carotid siphon) relative to restrictions of
      ultrasound techniques.

PMID- 23143180
TI  - APE1 Asp148Glu gene polymorphism and bladder cancer risk: a meta-analysis.
AB  - Published data regarding the association between the apurinic/apyrimidinic
      endonuclease 1 (APE1) Asp148Glu polymorphism and bladder cancer risk showed
      inconclusive results. This meta-analysis of literatures was performed to draw a
      more precise estimation of the relationship. We systematically searched PubMed,
      Embase, Elsevier and Springer for relevant articles with a time limit of Jan.
      2012. The strength of association between APE1 Asp148Glu polymorphism and bladder
      cancer risk was assessed by odds ratio (OR) with the corresponding 95 %
      confidence interval (95 % CI) using the software STATA(version10.0).A total of 11
      case-control studies including 4,292 cases and 4,761 controls based on the search
      criteria were included for analysis. Overall, for GG versus TT, the pooled OR was
      0.952 (95 % CI = 0.778-1.166), for the the G allele carriers (TG + GG) versus
      homozygote TT, the pooled OR was 0.984 (95 % CI = 0.897-1.078). In the stratified
      analysis by ethnicity, significantly risks were not found among Asians for GG
      versus TT (OR = 0.469; 95 % CI = 0.162-1.357) nor (TG + GG) versus TT (OR =
      0.921, 95 % CI = 0.742-1.143). Similarly, for non-Asians, significantly risks
      were also not found for GG versus TT (OR = 0.992; 95 % CI = 0.861-1.144) nor (TG
      + GG) versus TT (OR = 1.010, 95 % CI = 0.897-1.137). This meta-analysis suggested
      that the APE1 T1349G (Asp148Glu) polymorphism was not associated with bladder
      cancer risk among Asians nor non-Asians.

PMID- 23143181
TI  - Expression patterns of a cinnamyl alcohol dehydrogenase gene involved in lignin
      biosynthesis and environmental stress in Ginkgo biloba.
AB  - The cinnamyl alcohol dehydrogenase (CAD) is a key enzyme in lignin biosynthesis
      as it catalyzes the final step in the synthesis of monolignols. A cDNA sequence
      encoding the CAD gene was isolated from the leaves of Ginkgo biloba L, designated
      as GbCAD1. The full-length cDNA of GbCAD1 was 1,494 bp containing a 1,074 bp open
      reading frame encoding a polypeptide of 357 amino acids with a calculated
      molecular mass of 38.7 kDa and an isoelectric point of 5.74. Comparative and
      bioinformatic analyses revealed that GbCAD1 showed extensive homology with CADs
      from other gymnosperm species. Southern blot analysis indicated that GbCAD1
      belonged to a multi-gene family. Phylogenetic tree analysis revealed that GbCAD1
      shared the same ancestor in evolution with other CADs and had a further
      relationship with other gymnosperm species. GbCAD1 was an enzyme being pH
      dependent and temperature-sensitive, and showing a selected catalyzing. Tissue
      expression pattern analysis showed that GbCAD1 was constitutively expressed in
      stems and roots, especially in the parts of the pest and disease infection, with
      the lower expression being found in two- to four-year-old stem. Further analysis
      showed the change in lignin content had some linear correlation with the
      expression level of GbCAD1 mRNA in different tissues. The increased expression of
      GbCAD1 was detected when the seedling were treated with exogenous abscisic acid,
      salicylic acid, ethephon, ultraviolet and wounding. These results indicate that
      the GbCAD1 gene may play a role in the resistance mechanism to biotic and abiotic
      stresses as well as in tissue-specific developmental lignification.

PMID- 23143182
TI  - Effects of DGAT1 gene on meat and carcass fatness quality in Chinese commercial
      cattle.
AB  - This study was designed to investigate the candidate single nucleotide
      polymorphisms (SNPs) in the exon's region of bovine diacylglycerol O
      acyltransferase (DGAT1) gene using bioinformatics and experimental methods. A
      total of 17 SNPs were screened from public data resources and DNA sequencing.
      Three SNPs (c.572A>G, c.1241C>T and c.1416T>G) of these candidate SNPs were
      genotyped by created restriction site-polymerase chain reaction (CRS-PCR)
      methods. The gene-specific SNP markers and their effects on meat and carcass
      fatness quality traits were evaluated in Chinese commercial cattle. The c.572A>G
      and c.1416T>G significantly effected on backfat thickness, longissimus muscle
      area, marbling score, fat color and Warner-Bratzler shear force. No significant
      association was detected between the c.1241C>T and measured traits. Results from
      this study suggested that the SNP markers may be effective for the marker
      assisted selection of meat and carcass fatness quality traits, and added new
      evidence that DGAT1 gene is an important candidate gene for the improvement of
      meat and carcass fatness quality in beef cattle industry.

PMID- 23143183
TI  - Influence of pore water velocity on the release of carbofuran and fenamiphos from
      commercial granulates embedded in a porous matrix.
AB  - Pore water flow velocity can influence the processes involved in the contaminant
      transport between relative stagnant zones of porous media and their adjacent
      mobile zones. A particular case of special interest is the occurrence of high
      flow rates around the controlled release granules containing pesticides buried in
      soil. The release of the pesticides carbofuran and fenamiphos from commercial
      controlled release formulations (CRFs) was studied, comparing release tests in a
      finite volume of water with water flow release tests in saturated packed sand at
      different seepage velocities. For water release kinetics, the time taken for 50%
      of the pesticide to be released (T(50)) was 0.64 hours for carbofuran and 1.97
      hours for fenamiphos. In general, the release rate was lower in the porous matrix
      than in the free water tests. The faster release rate for carbofuran was
      attributed to its higher water diffusivity. The seepage velocity has a strong
      influence on the pesticide release rate. The dominant release mechanism varies
      with the progress of release. The evolution of the mechanism is discussed on the
      basis of the successive steps that involve the moving boundary of the dissolution
      front of the pesticide inside the granule, the concentration gradient inside the
      granule and the flow boundary layer resistance to solute diffusion around the
      granule. The pore water velocity influences the overall release dynamics.
      Therefore, seepage velocity should be considered in pesticide release to evaluate
      the risk of pesticide leaching, especially in scenarios with fast infiltration.

PMID- 23143184
TI  - How mobile is iodide in the Callovo-Oxfordian claystones under experimental
      conditions close to the in situ ones?
AB  - The iodide behaviour towards the Callovo-Oxfordian claystone was studied using
      batch and diffusion experiments under conditions which limited the artefacts
      cited in the literature to be responsible for the iodide uptake (i.e. the
      experiments were carried out under anoxic conditions with N(2)/CO(2) atmosphere
      with a monitoring of the iodine redox-state). The results show that all the
      radioactive iodine was (125)I(-), with no measurable activity for (125)IO(3)(-),
      which is known to have a higher affinity for the rock than iodide. Moreover, the
      batch experiments revealed no sorption, independently of the initial iodide
      concentration (from 10(-6) to 10(-3) mol L(-1)) and the contact time (up to 106
      days). Conversely, the diffusion experiments indicated a weak but measurable
      retention. The through-diffusion experiments led to distribution ratio values
      only significant (R(D)~0.05 mL g(-1)) for initial iodide concentration <= 10(-4)
      mol L(-1). Higher R(D) values were estimated from out-diffusion experiments,
      ranging from about 0.05 mL g(-1) for an initial concentration of 10(-3) mol L(-1)
      to 0.14 mL g(-1) for the lowest one. A retention phenomenon that could be
      reversible and kinetically-controlled was proposed to explain the differences in
      the extent of the iodide retardation of the two types of diffusion experiments.

PMID- 23143186
TI  - Unconventional promoters of catalytic activity in electrocatalysis.
AB  - Promoters and poisons for catalytic activity have been a subject of intensive
      research in both heterogeneous catalysis and electrocatalysis for decades, driven
      primarily by profound financial and societal implications involved because
      catalyzed reactions are at the center of many enterprises of chemical and
      petroleum industries. Consequently, there exist well-identified promoters and
      poisons, such as electropositive alkali elements for the former and
      electronegative later 2p elements for the latter, respectively. Research on
      catalytic promoters or poisons has traditionally been along the lines of these
      conventional classifications of promoters vs. poisons. However, this short
      Critical Review will not follow such traditional lines of reasoning, i.e., to
      discuss how the well-identified promoters can be better utilized and/or how the
      equally well-identified poisons can be eliminated or better tolerated. Rather, it
      will focus on cases that highlight an emerging area of research in which many
      traditional poisoning species have been used to promote catalytic activity, which
      include recent work on using sulfur and poly(vinylpyrrolidone) (PVP) as catalytic
      promoters carried out in the author's lab.

PMID- 23143187
TI  - Evaluation of miR-122 and other biomarkers in distinct acute liver injury in
      rats.
AB  - The detection of drug-induced hepatotoxicity remains an important safety issue in
      drug development. A liver-specific microRNA species, microRNA-122 (miR-122), has
      recently shown potential for predicting liver injury in addition to the standard
      hepatic injury biomarkers. The objective of this study was to measure miR-122
      together with several other liver markers in distinct settings of acute liver
      toxicity in rats to determine the value of miR-122 as a biomarker for liver
      injury in this species. Rats were exposed to 3 well-established liver toxicants
      (acetaminophen, allyl alcohol, and alpha-naphthyl isothiocyanate), a liver-enzyme
      inducer (phenobarbital), or a cardiotoxicant (doxorubicin). There was a clear
      increase in plasma miR-122 following administration of acetaminophen, allyl
      alcohol, and alpha-naphthyl isothiocyanate. The response of miR-122 paralleled
      that of other markers and was consistent with liver injury as indicated by
      histopathological evaluation. Furthermore, the changes in miR-122 were detected
      earlier than standard liver injury markers and exhibited a wide dynamic range. In
      contrast, miR-122 responses to phenobarbital and doxorubicin were low. Based on
      these findings, miR-122 shows significant promise and may provide added value for
      assessing liver toxicity in drug development. 

PMID- 23143188
TI  - Toxicologic pathology in the 21st century.
AB  - Toxicology is and will be heavily influenced by advances in many scientific
      disciplines. For toxicologic pathology, particularly relevant are the increasing
      array of molecular methods providing deeper insights into toxicity pathways, in
      vivo imaging techniques visualizing toxicodynamics and more powerful computers
      anticipated to allow (partly) automated morphological diagnoses. It appears
      unlikely that, in a foreseeable future, animal studies can be replaced by in
      silico and in vitro studies or longer term in vivo studies by investigations of
      biomarkers including toxicogenomics of shorter term studies, though the
      importance of such approaches will continue to increase. In addition to changes
      based on scientific progress, the work of toxicopathologists is and will be
      affected by social and financial factors, among them stagnating budgets,
      globalization, and outsourcing. The number of toxicopathologists in North
      America, Europe, and the Far East is not expected to grow. Many
      toxicopathologists will likely spend less time at the microscope but will be more
      heavily involved in early research activities, imaging, and as generalists with a
      broad biological understanding in evaluation and management of toxicity.
      Toxicologic pathology will remain important and is indispensable for validation
      of new methods, quality assurance of established methods, and for areas without
      good alternative methods. 

PMID- 23143189
TI  - In vitro and in vivo studies of pharmacokinetics and antitumor efficacy of D07001
      F4, an oral gemcitabine formulation.
AB  - PURPOSE: The chemotherapy agent gemcitabine is currently administered
      intravenously because the drug has poor oral bioavailability. In order to assess
      the pharmacokinetics and antitumor activity of D07001-F4, a new self
      microemulsifying oral drug delivery system preparation of gemcitabine, this study
      was performed to compare the effect of D07001-F4 with administered gemcitabine in
      vitro and in vivo. METHODS: D07001-F4 pharmacokinetics was examined by evaluation
      of in vitro deamination of D07001-F4 and gemcitabine hydrochloride by recombinant
      human cytidine deaminase (rhCDA) and in vivo evaluation of D07001-F4
      pharmacokinetics in mice. Antitumor activity was evaluated by comparing the
      effect of D07001-F4 and gemcitabine hydrochloride in inhibiting growth in nine
      cancer cell lines and by examining the effect of D07001-F4 and gemcitabine in two
      xenograft tumor models in mice. RESULTS: In vitro deamination of D07001-F4 by
      rhCDA was 3.3-fold slower than deamination of gemcitabine hydrochloride. Growth
      inhibition by D07001-F4 of 7 of the 8 cancer cell lines was increased compared
      with that seen with gemcitabine hydrochloride, and D07001-F4 inhibited the growth
      of pancreatic and colon cancer xenografts. In vivo pharmacokinetics showed the
      oral bioavailability of D07001-F4 to be 34%. CONCLUSIONS: D07001-F4 was effective
      against several cancer types, was metabolized more slowly than gemcitabine
      hydrochloride, and exhibited enhanced oral bioavailability.

PMID- 23143190
TI  - Triplet combination with paclitaxel, cisplatin and 5-FU is effective in
      metastatic and/or recurrent nasopharyngeal carcinoma.
AB  - PURPOSE: Platinum-based chemotherapy is the recognized first-line treatment for
      metastatic nasopharyngeal carcinoma (NPC). However, no standard treatment
      regimens have been established. This phase II study was designed to evaluate the
      efficacy and safety of a paclitaxel, cisplatin and 5-FU combination in metastatic
      and/or recurrent NPC. METHODS: Patients with evaluable metastatic and/or
      recurrent NPC were entered into this study. Treatment consisted of paclitaxel at
      a dose of 135 mg/m(2) on day 1, cisplatin 25 mg/m(2)/day from day 1 to day 3 and
      5-FU-continuous infusion for 120 h at a variable dosage from 600 to 1,000
      mg/m(2)/day according to prior radiation. This regimen was repeated every 3
      weeks. RESULTS: A total of 95 patients were enrolled; 92 patients were evaluable
      for response. The overall response and disease control rates were 78.9 and 93.6
      %, respectively. At a median follow-up of 24.8 months, the respective median
      overall survival (OS) and progression-free survival were 22.7 months (95 % CI
      18.6-26.9 months) and 8.6 months (95 % CI 7.7-9.5 months). Toxicities were
      moderate and manageable. Grade 3/4 toxicities included leucopenia (14.7 %),
      neutropenia (17.9 %), anemia (3.2 %), thrombocytopenia (6.4 %), nausea (4.2 %),
      vomiting (9.5 %), stomatitis (9.5 %), diarrhea (3.2 %), aminotransferase (2.2 %)
      and sensory neuropathy (3.2 %). CONCLUSION: Triplet combination chemotherapy with
      paclitaxel, cisplatin and 5-FU is an effective and safe option in the front-line
      treatment for recurrent and/or metastatic NPC. The encouraging results with high
      response rate and long OS suggest that this regimen might be especially
      considered where tumor shrinkage is required.

PMID- 23143191
TI  - Desminopathies: pathology and mechanisms.
AB  - The intermediate filament protein desmin is an essential component of the extra
      sarcomeric cytoskeleton in muscle cells. This three-dimensional filamentous
      framework exerts central roles in the structural and functional alignment and
      anchorage of myofibrils, the positioning of cell organelles and signaling events.
      Mutations of the human desmin gene on chromosome 2q35 cause autosomal dominant,
      autosomal recessive, and sporadic myopathies and/or cardiomyopathies with marked
      phenotypic variability. The disease onset ranges from childhood to late
      adulthood. The clinical course is progressive and no specific treatment is
      currently available for this severely disabling disease. The muscle pathology is
      characterized by desmin-positive protein aggregates and degenerative changes of
      the myofibrillar apparatus. The molecular pathophysiology of desminopathies is a
      complex, multilevel issue. In addition to direct effects on the formation and
      maintenance of the extra-sarcomeric intermediate filament network, mutant desmin
      affects essential protein interactions, cell signaling cascades, mitochondrial
      functions, and protein quality control mechanisms. This review summarizes the
      currently available data on the epidemiology, clinical phenotypes, myopathology,
      and genetics of desminopathies. In addition, this work provides an overview on
      the expression, filament formation processes, biomechanical properties, post
      translational modifications, interaction partners, subcellular localization, and
      functions of wild-type and mutant desmin as well as desmin-related cell and
      animal models.

PMID- 23143193
TI  - Novel macro-microporous gelatin scaffold fabricated by particulate leaching for
      soft tissue reconstruction with adipose-derived stem cells.
AB  - The restoration of body contours as shaped by adipose tissue remains a clinical
      challenge specifically in patients who have experienced loss of contour due to
      trauma, surgical removal of tumours or congenital abnormalities. We have
      developed a novel macro-microporous biomaterial for use in soft tissue re-bulking
      and augmentation. Alginate beads provided the pore template for the construct.
      Incorporation, and subsequent dissolution, of the beads within a 7 % (w/v)
      gelatin matrix, produced a highly porous scaffold with an average pore size of
      2.01 +/- 0.08 mm. The ability of this scaffold to support the in vitro growth and
      differentiation of human adipose-derived stem cells (ADSCs) was then
      investigated. Histological analysis confirmed that the scaffold itself provided a
      suitable environment to support the growth of ADSCs on the scaffold walls. When
      delivered into the macropores in a fibrin hydrogel, ADSCs proliferated and filled
      the pores. In addition, ADSCs could readily be differentiated along the
      adipogenic lineage. These results therefore describe a novel scaffold that can
      support the proliferation and delivery of ADSCs. The scaffold is the first stage
      in developing a clinical alternative to current treatment methods for soft tissue
      reconstruction.

PMID- 23143192
TI  - Tumor angiogenesis and anti-angiogenic therapy in malignant gliomas revisited.
AB  - The cellular and molecular mechanisms of tumor angiogenesis and its prospects for
      anti-angiogenic cancer therapy are major issues in almost all current concepts of
      both cancer biology and targeted cancer therapy. Currently, (1) sprouting
      angiogenesis, (2) vascular co-option, (3) vascular intussusception, (4)
      vasculogenic mimicry, (5) bone marrow-derived vasculogenesis, (6) cancer stem
      like cell-derived vasculogenesis and (7) myeloid cell-driven angiogenesis are all
      considered to contribute to tumor angiogenesis. Many of these processes have been
      described in developmental angiogenesis; however, the relative contribution and
      relevance of these in human brain cancer remain unclear. Preclinical tumor models
      support a role for sprouting angiogenesis, vascular co-option and myeloid cell
      derived angiogenesis in glioma vascularization, whereas a role for the other four
      mechanisms remains controversial and rather enigmatic. The anti-angiogenesis drug
      Avastin (Bevacizumab), which targets VEGF, has become one of the most popular
      cancer drugs in the world. Anti-angiogenic therapy may lead to vascular
      normalization and as such facilitate conventional cytotoxic chemotherapy.
      However, preclinical and clinical studies suggest that anti-VEGF therapy using
      bevacizumab may also lead to a pro-migratory phenotype in therapy resistant
      glioblastomas and thus actively promote tumor invasion and recurrent tumor
      growth. This review focusses on (1) mechanisms of tumor angiogenesis in human
      malignant glioma that are of particular relevance for targeted therapy and (2)
      controversial issues in tumor angiogenesis such as cancer stem-like cell-derived
      vasculogenesis and bone-marrow-derived vasculogenesis.

PMID- 23143194
TI  - Stress analysis in oral obturator prostheses: imaging photoelastic.
AB  - Maxillary defects resulting from cancer, trauma, and congenital malformation
      affect the chewing efficiency and retention of dentures in these patients. The
      use of implant-retained palatal obturator dentures has improved the self-esteem
      and quality of life of several subjects. We evaluate the stress distribution of
      implant-retained palatal obturator dentures with different attachment systems by
      using the photoelastic analysis images. Two photoelastic models of the maxilla
      with oral-sinus-nasal communication were fabricated. One model received three
      implants on the left side of the alveolar ridge (incisive, canine, and first
      molar regions) and the other did not receive implants. Afterwards, a conventional
      palatal obturator denture (control) and two implant-retained palatal obturator
      dentures with different attachment systems (O-ring; bar-clip) were constructed.
      Models were placed in a circular polariscope and a 100-N axial load was applied
      in three different regions (incisive, canine, and first molar regions) by using a
      universal testing machine. The results were photographed and analyzed
      qualitatively using a software (Adobe Photoshop). The bar-clip system exhibited
      the highest stress concentration followed by the O-ring system and conventional
      denture (control). Images generated by the photoelastic method help in the oral
      rehabilitator planning.

PMID- 23143195
TI  - Pioglitazone and risk of bladder cancer: clarification of the design of the
      French study. Reply to Perez AT [letter].

PMID- 23143196
TI  - Autophagy and role in asthma.
AB  - PURPOSE OF REVIEW: Asthma is a common worldwide respiratory illness with
      significant morbidity and mortality. The disease is characterized by airway
      inflammation with involvement of multiple biological pathways. Genetic
      predisposition and increased susceptibility to severe respiratory viral
      infections are well known clinical features of asthma. Autophagy is an
      evolutionarily conserved cellular degradation process with significant impact on
      immunity and antiviral response. In this review we have described the role of
      autophagy in immune cell survival, proliferation and function. Autophagy has
      complex effects on immune response involved in inflammation, specifically Th2
      immune response. Common respiratory viruses are associated with increased
      morbidity and mortality in asthmatic patients. RECENT FINDINGS: We describe
      recent studies showing the effect of autophagy on replication and immune response
      to common respiratory viruses. The role of autophagy in asthma has recently been
      investigated. Two studies have been published describing the association of
      autophagy with asthma. Genetic polymorphism in specific autophagy genes is
      associated with asthma and influences gene expression in an experimental in-vivo
      model. SUMMARY: These studies provide us with a window into the possible role of
      autophagy in asthma and offer new clues to pathogenesis. Modulation of autophagy
      has the potential to develop into a new therapeutic avenue to treat this common
      respiratory ailment.

PMID- 23143197
TI  - The role of inhaled corticosteroids in management of asthma in infants and
      preschoolers.
AB  - PURPOSE OF REVIEW: This review analyses published data on the treatment of
      wheezing in infants and preschoolers with inhaled corticosteroids (ICS),
      including the effect in subgroups of patients such as 'multiple trigger wheeze'
      and 'episodic viral wheeze'. RECENT FINDINGS: Therapy with ICS at daily doses of
      100-200  MUg results in significant clinical improvements in several outcomes in
      preschoolers and infants suspected of having asthma (multiple trigger wheeze).
      Such treatment is normally considered well tolerated. Although not well studied,
      higher daily doses may be associated with measurable effects on growth, which are
      not cumulative with continued treatment. In children who only wheeze in
      association with viral infections (episodic viral wheeze), preemptive treatment
      with high doses of ICS has demonstrated significant clinical effects on several
      outcomes, whereas lower doses seem to have little effect. Intermittent use of
      high doses of ICS has been associated with significant reductions in height and
      weight gain over 1 year. SUMMARY: The review illustrates the complexity of
      treating wheezing in infants and preschoolers and interpreting the study results.
      It emphasizes the need for more studies in clinical subgroups, more long-term
      studies and dose-response studies to assess the optimal doses and safety of
      intermittent as well as regular ICS treatment.

PMID- 23143198
TI  - Medication adherence in asthma patients.
AB  - PURPOSE OF REVIEW: Although current asthma guidelines stress the importance of
      assessing and enhancing adherence to asthma treatment, medication adherence rates
      in asthma patients are consistently low in practice. In this review, we summarize
      current literature on method of measurement, prevalence, outcome and intervention
      of medication adherence in asthma patients. RECENT FINDINGS: Nonadherence to
      prescribed treatment continues to be a frequent problem in patients with asthma
      even in recent years. Objective measurement of adherence should be implemented
      whenever possible. Review of pharmacy refill data or electronic monitoring of
      inhaler actuation may be a preferred method to assess adherence. Educational
      programmes should be specifically designed to address the unmet need and specific
      reasons for nonadherence for the target population. Large, well designed clinical
      trials to assess the efficacy of remote electronic monitoring and reminder
      systems to improve adherence are needed. SUMMARY: There is an urgent clinical
      need for systematic, proven methods to assess and address medication nonadherence
      in asthma patients.

PMID- 23143199
TI  - Induced sputum in asthma:  diagnostic and therapeutic implications.
AB  - PURPOSE OF REVIEW: Induced sputum provides a noninvasive way of assessing airway
      disease. This has led to the identification of different phenotypes of asthma and
      the potential for individualized treatment targeted at specific pathological
      processes. However, practical issues limit the frequent use of this technique.
      This review assesses the extent to which induced sputum can distinguish between
      asthma phenotypes and guide treatment. RECENT FINDINGS: Although the short-term
      repeatability of sputum analysis is good, recent research has shown a great deal
      of variability in sputum inflammatory profiles over follow-up periods of several
      months to a few years. In particular, the distinction between eosinophilic and
      noneosinophilic asthma is not consistent in many individuals. These findings
      suggest that persistent asthma phenotypes cannot be determined using a single
      sputum sample. Recent studies have also cast doubt on previous findings that
      noneosinophilic asthma is unresponsive to corticosteroid treatment. SUMMARY:
      Sputum inflammatory profiles are not consistent over time and a persistent asthma
      phenotype cannot be reliably determined using a single induced sputum. Because
      time and cost issues prohibit frequent induced sputum analyses in most clinical
      settings, these findings limit the diagnostic and therapeutic value of sputum
      analysis for clincal practice.

PMID- 23143202
TI  - Synthesis, catalysis, surface chemistry and structure of bimetallic
      nanocatalysts.

PMID- 23143201
TI  - Sulfhydryl-dependent dimerization of soluble guanylyl cyclase modulates the
      relaxation of porcine pulmonary arteries to nitric oxide.
AB  - The dimeric status of nitric oxide (NO)-sensitive soluble guanylyl cyclase (sGC)
      is obligatory for its catalyzing activity to synthesis the second messenger
      cyclic guanosine monophosphate (cGMP), which leads to vasodilatation. The present
      study was conducted to determine whether or not the dimerization of sGC is
      modulated by thiol-reducing agents and its influences on relaxation of pulmonary
      arteries caused by NO. The dimers and monomers of sGC and cGMP-dependent protein
      kinase (PKG) were analyzed by Western blotting. The intracellular cGMP content
      was measured by enzyme-linked immunosorbent assay. Relaxations of isolated
      porcine pulmonary arteries were determined by organ chamber technique. Protein
      levels of sGC dimers were decreased by thiol reductants dithiothreitol (DTT),
      reduced L-glutathione, L-cysteine, and tris(2-carboxyethyl)phosphine (TCEP),
      associated with decreased cGMP elevation, attenuated relaxations to NO. DTT at
      concentrations that affected sGC dimerization and activity showed no effect on
      PKG dimerization nor relaxation to 8-Br-cGMP. Hypoxia decreased the dimerization
      and activity of sGC of the arteries. The suppression of DTT and TCEP on sGC
      dimerization and activity was augmented by hypoxia. In the presence of DTT and
      TCEP, relaxations of porcine pulmonary artery caused by NO were significantly
      less under hypoxia compared with those under normoxia. These results suggest that
      the dimerization and activity of sGC along with NO-induced vasodilatation can be
      modulated in a thiol-dependent manner. Such a mechanism may be involved in the
      diminished response of pulmonary arteries to NO under hypoxia.

PMID- 23143203
TI  - Post-recurrence survival of patients with non-small-cell lung cancer after
      curative resection with or without induction/adjuvant chemotherapy.
AB  - OBJECTIVES: Recently, the prognosis of patients with non-small-cell lung cancer
      (NSCLC) has improved, thanks to the standardization of adjuvant chemotherapy and
      the introduction of molecular-targeted drugs, notably epidermal growth factor
      receptor (EGFR) tyrosine kinase inhibitors and other new anti-cancer agents.
      However, the survival characteristics and prognosis of patients with recurrent
      NSCLC after curative resection are not well understood. METHODS: Of the 430
      consecutive patients with NSCLC who underwent complete surgical resection at our
      institution between January 2004 and July 2011, we included 76 patients with
      recurrence whose post-recurrence treatment and outcome could be confirmed. We
      then retrospectively evaluated the effect of prognostic factors on post
      recurrence survival. RESULTS: There were 50 men and 26 women, and the median age
      at recurrence was 74.5 years. The median time from surgical resection to
      recurrence was 12.7 months. Thirty-eight of the 76 (50%) patients underwent
      multimodality treatment with surgery and preoperative and/or postoperative
      chemotherapy as their initial treatment. For recurrence, systemic chemotherapy
      was administered to 64 (84%) patients, and the disease control rate for first
      line chemotherapy was 55%. The 1- and 2-year post-recurrence survival rates were
      68.3 and 45.8%, respectively, and the median post-recurrence survival time was
      17.7 months. Six independent prognostic factors were identified: wild-type EGFR,
      no adjuvant chemotherapy for the primary lung cancer, age >= 80 years at
      recurrence, a poor Eastern Cooperative Oncology Group performance status at
      recurrence, symptomatic at recurrence and no systemic chemotherapy for
      recurrence, which significantly decreased the post-recurrence survival.
      CONCLUSIONS: The prognosis of patients with NSCLC recurrence after surgery is
      currently improving. Our results suggested two new prognostic factors, adjuvant
      chemotherapy and EGFR mutations, neither of which have been previously reported.
      Treatment strategies for postoperative recurrence should be established based on
      a more detailed subdivision of factors, such as histology and molecular markers,
      in the future.

PMID- 23143204
TI  - Is home monitoring of international normalised ratio safer than clinic-based
      monitoring?
AB  - A best evidence topic was written according to a structured protocol, to answer
      the question: 'In patients taking warfarin, is home self-monitoring of
      international normalized ratio (INR) safer than clinic-based testing in reducing
      bleeding, thrombotic events and death?' Altogether, 268 papers were found using
      the reported search. Five papers represented the highest level of evidence to
      answer the clinical question (four systematic reviews with meta-analysis and one
      meta-analysis). The authors, journal, date and country of publication, patient
      group studied, study type, relevant outcomes and results of these papers are
      tabulated. The principal outcomes of interest were death, major haemorrhage,
      major thromboembolism, and time (or percentage time) spent within the therapeutic
      range, compared between self-monitoring/self-management and conventional
      management. Self-monitoring/self-management was associated with a significantly
      reduced risk of all-cause mortality of 26-42%. All meta-analyses reported on
      major thromboembolism, finding significant reductions in risk of ~50%. One meta
      analysis found a 35% reduction in the risk of major haemorrhage, with the other
      four studies finding no significant difference. Only one study found self
      monitoring/self-management to be associated with a significantly greater
      proportion of time within range, with another finding no significant difference
      in either the percentage of therapeutic results or in the time within range. The
      remaining two could not combine data for meta-analysis owing to methodological
      heterogeneity. We conclude that self-monitoring/self-management appears to be
      safer than conventional management. It is associated with consistently lower
      rates of thromboembolism and may also be associated with reduced risk of bleeding
      and death. This supports the updated guidance from the American College of Chest
      Physicians, recommending self-management of INR for patients who are both
      competent and motivated.

PMID- 23143205
TI  - Aortic valve replacement with autologous pericardium: long-term follow-up of 15
      patients and in vivo histopathological changes of autologous pericardium.
AB  - OBJECTIVES: The study aimed to assess the long-term follow-up of patients with an
      autologous pericardial aortic valve (APAV) replacement and to analyse in vivo
      histopathological changes in implanted APAVs. METHODS: From 1996 to 1997, 15
      patients (mean age, 34 years) underwent aortic valve replacement with the
      glutaraldehyde-treated autologous pericardium. All patients were followed up
      after discharge. The excised APAVs were processed for haematoxylin-eosin,
      Victoria blue-van Gieson and immunohistochemical staining. RESULTS: The mean
      clinical follow-up was 11.43 +/- 4.50 years. APAV-related in-hospital and late
      mortalities were both 0%. Five (33%) patients required reoperation because of a
      prolapse of the right coronary cusp (n = 1), infective endocarditis (n = 1) or
      fibrocalcific degeneration (n = 3). Freedom from endocarditis, fibrocalcific
      degeneration and reoperation at the end of follow-up was 93, 80 and 67%,
      respectively. The remaining 10 patients were alive and well with a mean New York
      Heart Association class of 1.10 +/- 0.32 and normally functioning aortic valves
      (peak pressure gradient: 7.70 +/- 3.41 mmHg; mean pressure gradient: 1.79 +/-
      0.64 mmHg). Histopathology revealed that (i) a thin factor VIII-positive layer
      (endothelialization) was found on all non-endocarditis APAVs; (ii) pericardial
      cells in all APAVs were positive for alpha-smooth muscle actin (myofibroblast
      phenotype) and some cells in the fibrocalcific APAVs were positive for alkaline
      phosphatase (osteoblast phenotype) and (iii) an elastic band was found in 3 cases
      (in vivo >9 years). CONCLUSIONS: APAV replacement is a procedure with a low
      mortality. APAVs adapt to new environmental demands by producing an elastic band
      and by endothelialization, whereas myofibroblast/osteoblast transdifferentiation
      seems to be responsible for the fibrocalcification of APAVs.

PMID- 23143206
TI  - Large aneurysm of left coronary sinus of Valsalva presenting with effort-related
      ventricular fibrillation.
AB  - Sinus of Valsalva aneurysms are very rare and are often asymptomatic. Clinical
      manifestations depend on associated complications, most commonly rupture or
      dissection. We describe the unusual case of a 46-year old presenting with
      exercise-induced ventricular fibrillation due to extrinsic compression of the
      left coronary artery. We also describe the surgical correction by valve-sparing
      aortic root replacement.

PMID- 23143207
TI  - Dose-finding study of hepatic arterial infusion of oxaliplatin-based treatment in
      patients with advanced solid tumors metastatic to the liver.
AB  - BACKGROUND: Liver metastases in patients with cancer are associated with poor
      survival. We hypothesized that hepatic arterial infusion (HAI) of oxaliplatin
      combination therapy would have antitumor activity in these patients. PATIENTS AND
      METHODS: Patients with advanced cancer and predominant liver metastases were
      treated on a phase I study of HAI oxaliplatin in combination with systemic
      bevacizumab, with or without HAI or systemic fluorouracil and/or leucovorin
      and/or cetuximab. Patients were divided into two treatment arms according to KRAS
      mutational status and physician choice. A "3 + 3" design was used. RESULTS: Among
      76 patients (median age 61 years; 34 women; median number of prior therapies 4),
      the most common cancer was colorectal (CRC) (n = 58). Overall, the only dose
      limiting toxicity was Grade 3 diarrhea (n = 2). The most common treatment-related
      toxicities were hypertension (n = 40), nausea (n = 29), fatigue (n = 28), and
      transaminitis (n = 26). Of 76 patients, one (1 %) had a complete response (CR),
      12 (16 %) had a partial response (PR), and 12 (16 %) had SD for >= 6 months
      (total CR/PR/SD >= 6 months 25/76 = 33 %). In CRC (n = 58), total CR/PR/SD >= 6
      months was 31 % (n = 18). Both patients with pancreatic neuroendocrine tumors
      achieved a PR (24+ months) and a CR (6+ months). Time to treatment failure (TTF)
      on the current regimen was 3.5 versus 2.8 months on patients' prior systemic
      treatment (p = 0.37). CONCLUSIONS: HAI oxaliplatin combination therapy with 5
      fluorouracil, leucovorin, bevacizumab, and/or cetuximab was well tolerated and
      had antitumor activity in selected heavily pretreated patients with predominant
      liver disease.

PMID- 23143208
TI  - Synthesis and characterization of some new Schiff base complexes of group 13
      elements, ab initio studies, cytotoxicity and reaction with hydrogen peroxide.
AB  - A novel tetradentate Schiff base, naphthabza-H2=N,N'-bis(naphthylidene)-2
      aminobenzylamine, and a series of aluminum(III), gallium(III), and indium(III)
      complexes with general formula, MLNO3, were synthesized and characterized by
      elemental analysis, 1H NMR, FT-IR, UV-Vis spectroscopy and thermogravimetric
      method. The product of the reaction of complexes with hydrogen peroxide was
      characterized by similar techniques. According to the ab initio calculations
      aluminum and gallium complexes have five-coordinated structures and indium
      complex is a six-coordinated one. Also, the growth inhibitory effects of the
      complexes toward K562 cancer cell line were measured and the results for these
      complexes are as follows: Al>Ga>In.

PMID- 23143209
TI  - Accurate ab initio study on the A2Pi, 1(4)Sigma+, 1(4)Pi, 2(4)Pi and 1(6)Sigma+
      electronic states of AlO radical including spin-orbit coupling.
AB  - The potential energy curves (PECs) of 15 Omega states generated from five Lambda
      S states (A2Pi, 1(4)Sigma+, 1(4)Pi, 2(4)Pi and 1(6)Sigma+) of AlO radical are
      studied in detail using high level ab initio quantum chemical method for the
      first time. All the PEC calculations are made by the complete active space self
      consistent field method, which is followed by the internally contracted
      multireference configuration interaction approach with the Davidson modification
      (MRCI+Q). The spin-orbit coupling effect is included by the Breit-Pauli
      Hamiltonian with the aug-cc-pCVTZ basis set. Convergent behavior is discussed and
      excellent convergence has been observed with respect to the basis sets and level
      of theory. To improve the quality of PECs, core-valence correlation and scalar
      relativistic corrections are taken into account. Core-valence correlation
      corrections are included employing a cc-pCVQZ basis set. Scalar relativistic
      corrections are calculated by the third-order Douglas-Kroll Hamiltonian
      approximation at the level of a cc-pV5Z basis set. All the PECs are extrapolated
      to the complete basis set limit by the total-energy extrapolation scheme. With
      these PECs including all the corrections used here, on the one hand, the
      spectroscopic parameters of all the Lambda-S and Omega states are calculated,
      which are in reasonable agreement with the experimental and other theoretical
      results; on the other hand, the vibrational levels and inertial rotation
      constants of X2Sigma+, A2Pi, B2Sigma+ Lambda-S states as well as A2Pi3/2 and
      A2Pi1/2 Omega states are determined, which also agree well with the measurements.
      The vibrational levels and inertial rotation constants of A(2)Pi3/2 and A2Pi1/2
      Omega states as well as the spectroscopic parameters of four Lambda-S states
      (1(4)Sigma+, 1(4)Pi, 2(4)Pi and 1(6)Sigma+) and their corresponding 13 Omega
      states can be expected to be reliable predicted ones.

PMID- 23143212
TI  - Social networks, social support, and burden in relationships, and mortality after
      breast cancer diagnosis in the Life After Breast Cancer Epidemiology (LACE)
      study.
AB  - Larger social networks have been associated with lower breast cancer mortality.
      The authors evaluated how levels of social support and burden influenced this
      association. We included 2,264 women from the Life After Cancer Epidemiology
      study who were diagnosed with early-stage, invasive breast cancer between 1997
      and 2000, and provided data on social networks (spouse or intimate partner,
      religious/social ties, volunteering, time socializing with friends, and number of
      first-degree female relatives), social support, and caregiving. 401 died during a
      median follow-up of 10.8 years follow-up with 215 from breast cancer. We used
      delayed entry Cox proportional hazards regression to evaluate associations. In
      multivariate-adjusted analyses, social isolation was unrelated to recurrence or
      breast cancer-specific mortality. However, socially isolated women had higher all
      cause mortality (HR = 1.34, 95 % CI: 1.03-1.73) and mortality from other causes
      (HR = 1.79, 95 % CI: 1.19-2.68). Levels of social support and burden modified
      associations. Among those with low, but not high, levels of social support from
      friends and family, lack of religious/social participation (HR = 1.58, 95 % CI:
      1.07-2.36, p = 0.02, p interaction = 0.01) and lack of volunteering (HR = 1.78,
      95 % CI: 1.15-2.77, p = 0.01, p interaction = 0.01) predicted higher all-cause
      mortality. In cross-classification analyses, only women with both small networks
      and low levels of support (HR = 1.61, 95 % CI: 1.10-2.38) had a significantly
      higher risk of mortality than women with large networks and high levels of
      support; women with small networks and high levels of support had no higher risk
      of mortality (HR = 1.13, 95 % CI: 0.74-1.72). Social networks were also more
      important for caregivers versus noncaregivers. Larger social networks predicted
      better prognosis after breast cancer, but associations depended on the quality
      and burden of family relationships.

PMID- 23143213
TI  - The association of breast density with breast cancer mortality in African
      American and white women screened in community practice.
AB  - The effect of breast density on survival outcomes for American women who
      participate in screening remains unknown. We studied the role of breast density
      on both breast cancer and other cause of mortality in screened women. Data for
      women with breast cancer, identified from the community-based Carolina
      Mammography Registry, were linked with the North Carolina cancer registry and NC
      death tapes for this study. Cause-specific Cox proportional hazards models were
      developed to analyze the effect of several covariates on breast cancer mortality
      namely, age, race (African American/White), cancer stage at diagnosis (in situ,
      local, regional, and distant), and breast density (BI-RADS( (r) ) 1-4). Two
      stratified Cox models were considered controlling for (1) age and race, and (2)
      age and cancer stage, respectively, to further study the effect of density. The
      cumulative incidence function with confidence interval approximation was used to
      quantify mortality probabilities over time. For this study, 22,597 screened women
      were identified as having breast cancer. The non-stratified and stratified Cox
      models showed no significant statistical difference in mortality between dense
      tissue and fatty tissue, while controlling for other covariate effects (p value =
      0.1242, 0.0717, and 0.0619 for the non-stratified, race-stratified, and cancer
      stage-stratified models, respectively). The cumulative mortality probability
      estimates showed that women with dense breast tissues did not have significantly
      different breast cancer mortality than women with fatty breast tissue, regardless
      of age (e.g., 10-year confidence interval of mortality probabilities for whites
      aged 60-69 white: 0.056-0.090 vs. 0.054-0.083). Aging, African American race, and
      advanced cancer stage were found to be significant risk factors for breast cancer
      mortality (hazard ratio >1.0). After controlling for cancer incidence, there was
      not a significant association between mammographic breast density and mortality,
      adjusting for the effects of age, race, and cancer stage.

PMID- 23143214
TI  - Prospective dual role of mesenchymal stem cells in breast tumor microenvironment.
AB  - Breast cancer tissue is a heterogeneous cellular milieu comprising cancer and
      host cells. The interaction between breast malignant and non-malignant cells
      takes place in breast tumor microenvironment (TM), and has a crucial role in
      breast cancer progression. In addition to cellular component of TM, it mainly
      consists of cytokines released by tumor cells. The tumor-tropic capacity of
      mesenchymal stem cells (MSCs) and their interaction with breast TM is an active
      area of investigation. In the present communication, the interplay between the
      breast resident adipose tissue-derived MSCs (B-ASCs) and breast TM was studied.
      It was found that a distinct subset of B-ASCs display a strong affinity for
      conditioned media (CM) from two breast cancer cell lines, MDA-MB 231 (MDA-CM) and
      MCF-7 (MCF-CM). The expressions of several cytokines including angiogenin, GM
      CSF, IL-6, GRO-alpha and IL-8 in MDA-CM and MCF-CM have been identified. Upon
      functional analysis a crucial role for GRO-alpha and IL-8 in B-ASCs migration was
      detected. The B-ASC migration was found to be via negative regulation of RECK and
      enhanced expression of MMPs. Furthermore, transcriptome analysis showed that
      migratory subpopulation express both pro- and anti-tumorigenic genes and
      microRNAs (miRNA). Importantly, we observed that the migratory cells exhibit
      similar gene and miRNA attributes as those seen in B-ASCs of breast cancer
      patients. These findings are novel and suggest that in breast cancer, B-ASCs
      migrate to the proximity of tumor foci. Characterization of the molecular
      mechanisms involved in the interplay between B-ASCs and breast TM will help in
      understanding the probable role of B-ASCs in breast cancer development, and could
      pave way for anticancer therapies.

PMID- 23143215
TI  - Emerging treatment options for the management of brain metastases in patients
      with HER2-positive metastatic breast cancer.
AB  - The widespread use of trastuzumab in the past decade has led to a significant and
      measureable improvement in the survival of patients with human epidermal growth
      factor receptor-2 (HER2) overexpressing breast cancer, and in many ways has
      redefined the natural history of this aggressive breast cancer subtype.
      Historically, survival in patients with HER2-positive disease was dictated by the
      systemic disease course, and what appears to be the central nervous system (CNS)
      tropism associated with HER2-amplified tumors was not clinically evident. With
      improved systemic control and prolonged survival, the incidence of brain
      metastases has increased, and CNS disease, often in the setting of well
      controlled extracranial disease, is proving to be an increasingly important and
      clinically challenging cause of morbidity and mortality in patients with HER2
      positive advanced breast cancer. This review summarizes the known clinical data
      for the systemic treatment of HER2-positive CNS metastases and includes
      information about ongoing clinical trials of novel therapies as well as emerging
      strategies for early detection and prevention.

PMID- 23143216
TI  - Effect of systemic celecoxib on human meningioma after intracranial
      transplantation into nude mice.
AB  - BACKGROUND: Meningiomas are mostly benign, but they may have a notorious tendency
      to recur when total resection is not possible. Systemic chemotherapeutical
      treatment has been largely disappointing. The treatment of meningiomas with the
      cyclooxygenase-2 (COX-2) inhibitor celecoxib showed inhibitory-growth effects in
      vitro and in vivo after subcutaneous transplantation into mouse. So far,
      celecoxib has never been tested in an orthotopic model of meningioma. In this
      work, we tested the effects of celecoxib on the growth of human benign
      meningiomas after transplantation into the prefrontal cortex of nude mice after
      confirming the inhibitory in vitro effect on these cells. METHODS: Primary cell
      cultures were stereotactically implanted into mice and were treated with 0, 750,
      or 1,500 ppm celecoxib for 3 months. The mice were then killed and blood was
      analyzed for celecoxib concentration. The mice brains were histologically
      processed for measurement of tumor volume, COX-2 expression, proliferation index
      (PI), intratumoral microvessel density (iMVD), and vascular endothelial growth
      factor (VEGF) expression. RESULTS: Treatment with celecoxib had no effect on
      tumor volume, despite the fact that we found a dose-dependent inhibitory effect
      on cell cultures and there was a sufficiently high celecoxib concentration in
      blood plasma and brain tissue. Additionally, celecoxib had neither an effect on
      COX-2 and VEGF expression nor on the PI and iMVD. CONCLUSIONS: Our findings
      suggest that celecoxib may not be effective on meningioma growth in clinical
      settings. In general, these results may indicate that the effect of treatment on
      brain tumors should not only be tested in a heterotopic environment but also in
      the orthotopic location of these tumors.

PMID- 23143217
TI  - Stability of latent classes in group-based trajectory modeling of depressive
      symptoms in mothers of children with epilepsy: an internal validation study using
      a bootstrapping procedure.
AB  - PURPOSE: The aim of this study was to utilize bootstrapping to investigate the
      robustness of latent class trajectories and risk factors of depressive symptoms
      among mothers of children with epilepsy. METHODS: Data were obtained from a
      national prospective cohort study (2004-09) of children newly diagnosed with
      epilepsy and their families in Canada (n = 339). Latent classes of depressive
      symptom trajectories were modeled using a semi-parametric group-based trajectory
      modeling approach. Multinomial logistic regression identified risk factors
      predicting trajectory group membership. RESULTS: Four trajectories were
      identified: low stable, borderline, moderate increasing, and high decreasing.
      Goodness of fit, posterior probabilities, and parameter estimates obtained with
      bootstrapping were not significantly different from the original sample.
      Calculation of the root mean square error demonstrated minimal non-ignorable bias
      for three parameter estimates, which was subsequently removed with additional
      sampling. Risk factors identified were identical for the original sample and the
      bootstrap, and differences in odds ratios, as calculated with the method of
      variance estimation recovery, were not significant. CONCLUSIONS: As examined
      using a bootstrapping procedure, group-based trajectory modeling offers a robust
      methodology to uncover potential heterogeneity in populations and identify high
      risk individuals.

PMID- 23143218
TI  - Phase I and clinical pharmacology study of bevacizumab, sorafenib, and low-dose
      cyclophosphamide in children and young adults with refractory/recurrent solid
      tumors.
AB  - PURPOSE: To determine the maximum-tolerated dose (MTD), dose-limiting toxicities
      (DLT), pharmacokinetics, and pharmacodynamics of sorafenib, bevacizumab, and low
      dose oral cyclophosphamide in children and young adults with recurrent/refractory
      solid tumors. EXPERIMENTAL DESIGN: Sorafenib dose was escalated from 90 to 110
      mg/m(2) twice daily with fixed doses of bevacizumab at 5 mg/kg every 3 weeks and
      cyclophosphamide at 50 mg/m(2) daily. Once sorafenib's MTD was established,
      bevacizumab dose was escalated. Each course was of 21 days. Pharmacokinetics and
      pharmacodynamics studies were conducted during the first course. RESULTS:
      Nineteen patients (11 males; median age, 9.2 years) received a median of four
      courses (range, 1-23). DLTs during course 1 included grade 3 rash (two),
      increased lipase (one), anorexia (one), and thrombus (one). With an additional 71
      courses of therapy, the most common toxicities >= grade 3 included neutropenia
      (nine), lymphopenia (nine), and rashes (four). Five of 17 evaluable patients had
      partial tumor responses, and five had disease stabilization (>2 courses). Median
      day 1 cyclophosphamide apparent oral clearance was 3.13 L/h/m(2). Median day 1
      sorafenib apparent oral clearance was 44 and 39 mL/min/m(2) at the 2 dose levels
      evaluated, and steady-state concentrations ranged from 1.64 to 4.8 mg/L.
      Inhibition of serum VEGF receptor 2 (VEGFR2) was inversely correlated with
      sorafenib steady-state concentrations (P = 0.019). CONCLUSION: The recommended
      phase II doses are sorafenib, 90 mg/m(2) twice daily; bevacizumab, 15 mg/kg q3
      weeks; and cyclophosphamide, 50 mg/m(2) once daily. This regimen is feasible with
      promising evidence of antitumor activity that warrants further investigation.

PMID- 23143219
TI  - The treatment of squamous anal carcinoma: guidelines of the Italian Society of
      Colo-Rectal Surgery.
AB  - The Italian society of colo-rectal surgery (SICCR) is dedicated to improving the
      study, prevention and management of the diseases of the colon, rectum and anus.
      One of the aims of the society is to establish guidelines to the treatment of
      these diseases. These guidelines are based on the international literature and on
      the best available evidence. Clinical practice guidelines are one of the most
      important instruments to provide therapeutic decision-making support, based on
      the best scientific evidence available at the time. Guidelines are advisory and
      not prescriptive, susceptible to continual variations secondary to innovations
      and new scientific evidence. These guidelines are a guide for all colo-rectal
      surgeons and physicians who approach anal cancer.

PMID- 23143220
TI  - The influence of RAPTA moieties on the antiproliferative activity of peripheral
      functionalised poly(salicylaldiminato) metallodendrimers.
AB  - Cationic N,O-chelating dendrimers functionalised on the periphery with RAPTA-like
      (ruthenium(II)-arene-1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane) moieties have
      been synthesised and characterised using NMR and IR spectroscopy, elemental
      analysis and MALDI-TOF/HR-ESI mass spectrometry. Metallodendrimers from the first
      to the fourth-generation containing up to 32 peripheral ruthenium-arene-PTA
      moieties were obtained. Model mononuclear analogues, [{Ru(eta(6)-p
      cymene)((C(7)H(5)NO)-kappa(2)-N,O)(PTA)}((CH(2))(3))][PF(6)] and
      [{Ru(eta(6)hexamethylbenzene)((C(7)H(5)NO)-kappa(2)
      N,O)(PTA)}((CH(2))(3))][PF(6)], have been prepared and their structures were
      determined by single crystal X-ray diffraction analysis. The cytotoxicities of
      the metallodendrimers and their mononuclear analogues were established on A2780
      and A2780cisR human ovarian carcinoma cancer cells and model human embryonic
      kidney (HEK) cells.

PMID- 23143221
TI  - Tonoplast of Beta vulgaris L. contains detergent-resistant membrane microdomains.
AB  - The experiments conducted on tonoplast of Beta vulgaris L. roots were performed
      to identify detergent-resistant lipid-protein microdomains (DRMs, interpreted as
      lipid rafts).The presence of DRMs can be found when dynamic clustering of
      sphingolipids, sterols, saturated fatty acids is registered, and the insolubility
      of these microdomains in nonionic detergents at low temperatures is proven. The
      elucidation of tonoplast microdomains has been based on results obtained with the
      aid of high-speed centrifuging in the sucrose gradient. The experiments have
      shown that tonoplast microdomains are rich in sphingolipids, free sterols and
      saturated fatty acids (such a lipid content is also typical of lipid-protein
      microdomains of other membranes), while only few phospholipids are present in
      tonoplast microdomains. The presence of microdomains has been confirmed by
      fluorescence and confocal microscopy using filipin and Laurdan as fluorescent
      probes. The experiments with Laurdan have shown that tonoplast microdomains are
      characterized by a high order compared to characteristics of the rest of the
      tonoplast. Thus, the presence of detergent-resistant lipid-protein microdomains
      in the tonoplast has been demonstrated.

PMID- 23143222
TI  - Immunohistochemical localization of caffeine in young Camellia sinensis (L.) O.
      Kuntze (tea) leaves.
AB  - The anatomical localization of caffeine within young Camellia sinensis leaves was
      investigated using immunohistochemical methods and confocal scanning laser
      microscopy. Preliminary fixation experiments were conducted with young C.
      sinensis leaves to determine which fixation procedure retained caffeine the best
      as determined by high-performance liquid chromatography analysis. High pressure
      freezing, freeze substitution, and embedding in resin was deemed the best
      protocol as it retained most of the caffeine and allowed for the samples to be
      sectioned with ease. Immunohistochemical localization with primary anti-caffeine
      antibodies and conjugated secondary antibodies on leaf sections proved at the
      tissue level that caffeine was localized and accumulated within vascular bundles,
      mainly the precursor phloem. With the use of a pressure bomb, xylem sap was
      collected using a micro syringe. The xylem sap was analyzed by thin-layer
      chromatography and the presence of caffeine was determined. We hypothesize that
      caffeine is synthesized in the chloroplasts of photosynthetic cells and
      transported to vascular bundles where it acts as a chemical defense against
      various pathogens and predators. Complex formation of caffeine with chlorogenic
      acid is also discussed as this may also help explain caffeine's localization.

PMID- 23143223
TI  - Thrombosis in vasculitis.
AB  - PURPOSE OF REVIEW: To review the association of thrombosis and vasculitis and
      discuss some of the proposed causal mechanisms. RECENT FINDINGS: It is becoming
      increasingly evident that various systemic inflammatory diseases such as
      vasculitis are associated with an increased risk of both venous and arterial
      thrombosis. Increasing evidence supports the use of immunosuppression in the
      management of venous thrombosis in Behcet's disease. An increased incidence of
      thromboembolic disease in antineutrophil cytoplasmic antibody-associated
      vasculitis has been recognized, especially during periods of active disease. In
      addition, a higher risk of ischemic heart disease in these patients has also been
      observed. As in giant cell arteritis, recent evidence supports the role of
      aspirin in the prevention of ischemic events in Takayasu's disease. SUMMARY:
      Thromboembolic disease is an important complication of several forms of systemic
      vasculitis, and it may result in significant morbidity and mortality. Many
      questions such as the role for screening of asymptomatic patients, prevention of
      thrombosis, and duration of anticoagulation in patients with vasculitis remain
      unanswered. Future studies exploring the mechanisms of thrombosis and its link to
      inflammation may provide insights in predicting patients at a higher risk for
      thrombosis and improve outcomes.

PMID- 23143224
TI  - The biology of the extracellular matrix:  novel insights.
AB  - PURPOSE OF REVIEW: Extracellular matrix (ECM) has both structural and regulatory
      roles. This update reviews the representative recent developments in diverse
      aspects of ECM biology relevant to inflammation, tissue destruction, fibrosis,
      and regeneration. RECENT FINDINGS: Biological regulation by ECM is emerging as a
      major research area, driven by several new directions. Sensing of mechanical cues
      provided by ECM was found to be crucial in regulating cell differentiation.
      Transforming growth factor-beta (TGF-beta) is a pivotal agent in fibrosis and
      inflammation. A combination of structural biology and cell biology provided novel
      insights on the mechanisms of its activation by cellular traction and ECM.
      Improved understanding of how fibrillin microfibrils and associated proteins
      regulated TGF-beta sequestration and activation was achieved by analysis of
      inherited connective tissue disorders having TGF-beta dysregulation as an
      underlying pathologic mechanism. Insights on microRNA-mediated ECM regulation
      suggest a key role for miR-29, for which potential therapeutic roles are
      emerging. Advances in understanding the ECM turnover by proteinases provided
      novel insights on cell regulation and identified useful disease biomarkers.
      SUMMARY: As a crucial modulator of cell behavior, ECM has exceptionally strong
      relevance and translational implications for human disease, opening novel
      opportunities for mechanistic understanding of disease pathogenesis as well as
      treatment.

PMID- 23143225
TI  - New concepts in the pathogenesis and treatment of vasculitis syndromes.

PMID- 23143226
TI  - Preliminary experience with Option inferior vena cava filter.
AB  - OBJECTIVES: To evaluate the safety and efficacy of Option inferior vena cava
      (IVC) filter during placement and short-term follow-up. METHODS: A total of 165
      patients (mean age: 60-years) who received Option IVC filter from June 2009 to
      July 2011 were included. In all, 42 patients presented with deep vein thrombosis
      (DVT), 26 with pulmonary embolism (PE), and 17 with both. All outcomes were
      examined until April 30, 2012. RESULTS: The filters were successfully deployed in
      161patients. During follow-up (mean, 9.5 +/- 0.68months), 10 patients were
      diagnosed with post-filter PE and 13 patients with DVT. There were no instances
      of fatal PE. Follow-up abdominal computed tomography was available in 60 patients
      and demonstrated filter-related problems in 8 patients (2: penetration of filter
      legs, 5: asymptomatic nonocclusive thrombus, and 1: caval occlusion). There were
      no instances of filter migration or fracture. In total, 27 filters were
      successfully retrieved after a mean of 5.27 +/- 0.76 months. CONCLUSION: The
      Option filter was effective and safe during implantation and short-term follow-up
      and associated with high technical success at retrieval.

PMID- 23143227
TI  - A unique hybrid approach to the treatment of an aberrant right subclavian artery
      aneurysm.
AB  - Aberrant right subclavian artery (ARSA) is an uncommon congenital anomaly that
      often becomes aneurysmal. The ARSAs are often asymptomatic but aneurysms arising
      in this location are potentially lethal. Due to the high morbidity and mortality
      rates associated with the traditional open repair methods, less invasive
      endovascular methods are becoming more popular. This is a case describing a
      unique hybrid repair of an aneurysmal ARSA in an asymptomatic male.

PMID- 23143228
TI  - Unravelling the enigma of selective vulnerability in neurodegeneration: motor
      neurons resistant to degeneration in ALS show distinct gene expression
      characteristics and decreased susceptibility to excitotoxicity.
AB  - A consistent clinical feature of amyotrophic lateral sclerosis (ALS) is the
      sparing of eye movements and the function of external sphincters, with
      corresponding preservation of motor neurons in the brainstem oculomotor nuclei,
      and of Onuf's nucleus in the sacral spinal cord. Studying the differences in
      properties of neurons that are vulnerable and resistant to the disease process in
      ALS may provide insights into the mechanisms of neuronal degeneration, and
      identify targets for therapeutic manipulation. We used microarray analysis to
      determine the differences in gene expression between oculomotor and spinal motor
      neurons, isolated by laser capture microdissection from the midbrain and spinal
      cord of neurologically normal human controls. We compared these to
      transcriptional profiles of oculomotor nuclei and spinal cord from rat and mouse,
      obtained from the GEO omnibus database. We show that oculomotor neurons have a
      distinct transcriptional profile, with significant differential expression of
      1,757 named genes (q < 0.001). Differentially expressed genes are enriched for
      the functional categories of synaptic transmission, ubiquitin-dependent
      proteolysis, mitochondrial function, transcriptional regulation, immune system
      functions, and the extracellular matrix. Marked differences are seen, across the
      three species, in genes with a function in synaptic transmission, including
      several glutamate and GABA receptor subunits. Using patch clamp recording in
      acute spinal and brainstem slices, we show that resistant oculomotor neurons show
      a reduced AMPA-mediated inward calcium current, and a higher GABA-mediated
      chloride current, than vulnerable spinal motor neurons. The findings suggest that
      reduced susceptibility to excitotoxicity, mediated in part through enhanced
      GABAergic transmission, is an important determinant of the relative resistance of
      oculomotor neurons to degeneration in ALS.

PMID- 23143229
TI  - APP mutations in the Abeta coding region are associated with abundant cerebral
      deposition of Abeta38.
AB  - Abeta is the main component of amyloid deposits in Alzheimer disease (AD) and its
      aggregation into oligomers, protofibrils and fibrils is considered a seminal
      event in the pathogenesis of AD. Abeta with C-terminus at residue 42 is the most
      abundant species in parenchymal deposits, whereas Abeta with C-terminus at
      residue 40 predominates in the amyloid of the walls of large vessels. Abeta
      peptides with other C-termini have not yet been thoroughly investigated. We
      analysed Abeta38 in the brains of patients with Abeta deposition linked to
      sporadic and familial AD, hereditary cerebral haemorrhage with amyloidosis, or
      Down syndrome. Immunohistochemistry, confocal microscopy, immunoelectron
      microscopy, immunoprecipitation and the electrophoresis separation of low
      molecular weight aggregates revealed that Abeta38 accumulates consistently in the
      brains of patients carrying APP mutations in the Abeta coding region, but was not
      detected in the patients with APP mutations outside the Abeta domain, in the
      patients with presenilin mutations or in subjects with Down syndrome. In the
      patients with sporadic AD, Abeta38 was absent in the senile plaques, but it was
      detected only in the vessel walls of a small subset of patients with severe
      cerebral amyloid angiopathy. Our results suggest that APP mutations in the Abeta
      coding region favour Abeta38 accumulation in the brain and that the molecular
      mechanisms of Abeta deposition in these patients may be different from those
      active in patients with familial AD associated with other genetic defects and
      sporadic AD.

PMID- 23143230
TI  - High-resolution structure of AKR1a4 in the apo form and its interaction with
      ligands.
AB  - Aldo-keto reductase 1a4 (AKR1a4; EC 1.1.1.2) is the mouse orthologue of human
      aldehyde reductase (AKR1a1), the founding member of the AKR family. As an NADPH
      dependent enzyme, AKR1a4 catalyses the conversion of D-glucuronate to L-gulonate.
      AKR1a4 is involved in ascorbate biosynthesis in mice, but has also recently been
      found to interact with SMAR1, providing a novel mechanism of ROS regulation by
      ATM. Here, the crystal structure of AKR1a4 in its apo form at 1.64 A resolution
      as well as the characterization of the binding of AKR1a4 to NADPH and P44, a
      peptide derived from SMAR1, is presented.

PMID- 23143231
TI  - Influence of intermolecular contacts on the structure of recombinant prolidase
      from Thermococcus sibiricus.
AB  - Prolidases are peptidases that are specific for dipeptides with proline as the
      second residue. The structure of recombinant prolidase from the hyperthermophilic
      archaeon Thermococcus sibiricus (Tsprol) was determined at 2.6 A resolution. The
      homodimer of Tsprol is characterized by a complete lack of interactions between
      the N- and C-terminal domains of the two subunits and hence can be considered to
      be the most open structure when compared with previously structurally studied
      prolidases. This structure exists owing to intermolecular coordination bonds
      between cadmium ions derived from the crystallization solution and histidine
      residues of a His tag and aspartate and glutamate residues, which link the dimers
      to each other. This linking leads to the formation of a crystal with a loose
      packing of protein molecules and low resistance to mechanical influence and
      temperature increase.

PMID- 23143232
TI  - Structure of glycerol-3-phosphate dehydrogenase (GPD1) from Saccharomyces
      cerevisiae at 2.45 A resolution.
AB  - The interconversion of glycerol 3-phosphate and dihydroxyacetone phosphate by
      glycerol-3-phosphate dehydrogenases provides a link between carbohydrate and
      lipid metabolism and provides Saccharomyces cerevisiae with protection against
      osmotic and anoxic stress. The first structure of a glycerol-3-phosphate
      dehydrogenase from S. cerevisiae, GPD1, is reported at 2.45 A resolution. The
      asymmetric unit contains two monomers, each of which is organized with N- and C
      terminal domains. The N-terminal domain contains a classic Rossmann fold with the
      (beta-alpha-beta-alpha-beta)2 motif typical of many NAD+-dependent enzymes, while
      the C-terminal domain is mainly alpha-helical. Structural and phylogenetic
      comparisons reveal four main structure types among the five families of glycerol
      3-phosphate and glycerol-1-phosphate dehydrogenases and reveal that the
      Clostridium acetobutylican protein with PDB code 3ce9 is a glycerol-1-phosphate
      dehydrogenase.

PMID- 23143233
TI  - Solution structure of the cold-shock-like protein from Rickettsia rickettsii.
AB  - Rocky Mountain spotted fever is caused by Rickettsia rickettsii infection. R.
      rickettsii can be transmitted to mammals, including humans, through the bite of
      an infected hard-bodied tick of the family Ixodidae. Since the R. rickettsii
      genome contains only one cold-shock-like protein and given the essential nature
      of cold-shock proteins in other bacteria, the structure of the cold-shock-like
      protein from R. rickettsii was investigated. With the exception of a short alpha
      helix found between beta-strands 3 and 4, the solution structure of the R.
      rickettsii cold-shock-like protein has the typical Greek-key five-stranded beta
      barrel structure found in most cold-shock domains. Additionally, the R.
      rickettsii cold-shock-like protein, with a DeltaG of unfolding of 18.4 kJ mol(
      1), has a similar stability when compared with other bacterial cold-shock
      proteins.

PMID- 23143234
TI  - Structure of the recombinant BPTI/Kunitz-type inhibitor rShPI-1A from the marine
      invertebrate Stichodactyla helianthus.
AB  - The BPTI/Kunitz-type inhibitor family includes several extremely potent serine
      protease inhibitors. To date, the inhibitory mechanisms have only been studied
      for mammalian inhibitors. Here, the first crystal structure of a BPTI/Kunitz-type
      inhibitor from a marine invertebrate (rShPI-1A) is reported to 2.5 A resolution.
      Crystallization of recombinant rShPI-1A required the salt-induced dissociation of
      a trypsin complex that was previously formed to avoid intrinsic inhibitor
      aggregates in solution. The rShPI-1A structure is similar to the NMR structure of
      the molecule purified from the natural source, but allowed the assignment of
      disulfide-bridge chiralities and the detection of an internal stabilizing water
      network. A structural comparison with other BPTI/Kunitz-type canonical inhibitors
      revealed unusual phi angles at positions 17 and 30 to be a particular
      characteristic of the family. A significant clustering of phi and psi angle
      values in the glycine-rich remote fragment near the secondary binding loop was
      additionally identified, but its impact on the specificity of rShPI-1A and
      similar molecules requires further study.

PMID- 23143235
TI  - Structure of Escherichia coli RutC, a member of the YjgF family and putative
      aminoacrylate peracid reductase of the rut operon.
AB  - RutC is the third enzyme in the Escherichia coli rut pathway of uracil
      degradation. RutC belongs to the highly conserved YjgF family of proteins. The
      structure of the RutC protein was determined and refined to 1.95 A resolution.
      The crystal belonged to space group P2(1)2(1)2 and contained six molecules in the
      asymmetric unit. The structure was solved by SAD phasing and was refined to an
      Rwork of 19.3% (Rfree=21.7%). The final model revealed that this protein has a
      Bacillus chorismate mutase-like fold and forms a homotrimer with a hydrophobic
      cavity in the center of the structure and ligand-binding clefts between two
      subunits. A likely function for RutC is the reduction of peroxy-aminoacrylate to
      aminoacrylate as a part of a detoxification process.

PMID- 23143236
TI  - Room-temperature X-ray diffraction studies of cisplatin and carboplatin binding
      to His15 of HEWL after prolonged chemical exposure.
AB  - The anticancer complexes cisplatin and carboplatin are known to bind to both the
      Ndelta and the NE atoms of His15 of hen egg-white lysozyme (HEWL) in the presence
      of dimethyl sulfoxide (DMSO). However, neither binds in aqueous media after 4 d
      of crystallization and crystal growth, suggesting that DMSO facilitates
      cisplatin/carboplatin binding to the N atoms of His15 by an unknown mechanism.
      Crystals of HEWL cocrystallized with cisplatin in both aqueous and DMSO media, of
      HEWL cocrystallized with carboplatin in DMSO medium and of HEWL cocrystallized
      with cisplatin and N-acetylglucosamine (NAG) in DMSO medium were stored for
      between seven and 15 months. X-ray diffraction studies of these crystals were
      carried out on a Bruker APEX II home-source diffractometer at room temperature.
      Room-temperature X-ray diffraction data collection removed the need for
      cryoprotectants to be used, ruling out any effect that the cryoprotectants might
      have had on binding to the protein. Both cisplatin and carboplatin still bind to
      both the Ndelta and NE atoms of His15 in DMSO media as expected, but more detail
      for the cyclobutanedicarboxylate (CBDC) moiety of carboplatin was observed at the
      NE binding site. However, two molecules of cisplatin were now observed to be
      bound to His15 in aqueous conditions. The platinum peak positions were identified
      using anomalous difference electron-density maps as a cross-check with Fo-Fc OMIT
      electron-density maps. The occupancies of each binding site were calculated using
      SHELXTL. These results show that over time cisplatin binds to both N atoms of
      His15 of HEWL in aqueous media, whereas this binding is speeded up in the
      presence of DMSO. The implication of cisplatin binding to proteins after a
      prolonged period of time is an important consideration for the length of
      treatment in patients who are given cisplatin.

PMID- 23143237
TI  - In situ X-ray data collection from highly sensitive crystals of Pseudomonas
      putida PtxS in complex with DNA.
AB  - Pseudomonas putida PtxS is a member of the LacI protein family of transcriptional
      regulators involved in glucose metabolism. All genes involved in this pathway are
      clustered into two operons, kgu and gad. PtxS controls the expression of the kgu
      and gad operons as well as its own transcription. The PtxS operator is a perfect
      palindrome, 5'-TGAAACCGGTTTCA-3', which is present in all three promoters.
      Crystallization of native PtxS failed, and PtxS-DNA crystals were finally
      produced by the counter-diffusion technique. A portion of the capillary used for
      crystal growth was attached to the end of a SPINE standard cap and directly flash
      cooled in liquid nitrogen for diffraction tests. A full data set was collected
      with a beam size of 10*10 um. The crystal belonged to the trigonal space group
      P3, with unit-cell parameters a=b=213.71, c=71.57 A. Only unhandled crystals
      grown in capillaries of 0.1 mm inner diameter diffracted X-rays to 1.92 A
      resolution.

PMID- 23143238
TI  - Crystallization and preliminary X-ray analysis of the FliH-FliI complex
      responsible for bacterial flagellar type III protein export.
AB  - The bacterial flagellar proteins are translocated into the central channel of the
      flagellum by a specific protein-export apparatus for self-assembly at the distal
      growing end. FliH and FliI are soluble components of the export apparatus and
      form an FliH2-FliI heterotrimer in the cytoplasm. FliI is an ATPase and the FliH2
      FliI complex delivers export substrates from the cytoplasm to an export gate made
      up of six integral membrane proteins of the export apparatus. In this study, an
      FliHC fragment consisting of residues 99-235 was co-purified with FliI and the
      FliHC2-FliI complex was crystallized. Crystals were obtained using the hanging
      drop vapour-diffusion technique with PEG 400 as a precipitant. The crystals
      belonged to the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters
      a=133.7, b=147.3, c=164.2 A, and diffracted to 3.0 A resolution.

PMID- 23143239
TI  - Crystallization and preliminary crystallographic studies of the W2 domain of
      Drosophila melanogaster eukaryotic translation initiation factor 5C domain
      containing protein.
AB  - The Drosophila melanogaster eukaryotic translation initiation factor 5C domain
      containing protein (ECP) is composed of two independently folded domains which
      belong to the basic leucine-zipper and W2 domain-containing protein (BZW) family.
      Based on the sequence similarity between the C-terminal W2 domain of ECP and some
      eukaryotic translation initiation factors (such as eIF2BE, eIF4gamma, eIF5 etc.),
      ECP has been speculated to participate in the translation initiation process.
      Structural information on the C-terminal W2 domain of ECP would be helpful in
      understanding the specific cellular function of this protein. Here, the W2 domain
      of ECP was expressed and crystallized. Crystals grown by the hanging-drop vapour
      diffusion method diffracted to 2.70 A resolution and belonged to space group I4,
      with unit-cell parameters a=b=81.05, c=57.44 A. The Matthews coefficient
      suggested that there was one molecule per asymmetric unit in the crystal.

PMID- 23143240
TI  - Purification, crystallization and preliminary crystallographic analysis of human
      cystathionine beta-synthase.
AB  - Human cystathionine beta-synthase (CBS) is a pyridoxal-5'-phosphate-dependent
      hemeprotein, whose catalytic activity is regulated by S-adenosylmethionine. CBS
      catalyzes the beta-replacement reaction of homocysteine (Hcy) with serine to
      yield cystathionine. CBS is a key regulator of plasma levels of the thrombogenic
      Hcy and deficiency in CBS is the single most common cause of homocystinuria, an
      inherited metabolic disorder of sulfur amino acids. The properties of CBS
      enzymes, such as domain organization, oligomerization degree or regulatory
      mechanisms, are not conserved across the eukaryotes. The current body of
      knowledge is insufficient to understand these differences and their impact on CBS
      function and physiology. To overcome this deficiency, we have addressed the
      crystallization and preliminary crystallographic analysis of a protein construct
      (hCBS516-525) that contains the full-length CBS from Homo sapiens (hCBS) and just
      lacks amino-acid residues 516-525, which are located in a disordered loop. The
      human enzyme yielded crystals belonging to space group I222, with unit-cell
      parameters a=124.98, b=136.33, c=169.83 A and diffracting X-rays to a resolution
      of 3.0 A. The crystal structure appears to contain two molecules in the
      asymmetric unit which presumably correspond to a dimeric form of the enzyme.

PMID- 23143241
TI  - Purification, crystallization and preliminary crystallographic analysis of the
      full-length cystathionine beta-synthase from Apis mellifera.
AB  - Cystathionine beta-synthase (CBS) is a pyridoxal-5'-phosphate-dependent enzyme
      that catalyzes the first step of the transsulfuration pathway, namely the
      condensation of serine with homocysteine to form cystathionine. Mutations in the
      CBS gene are the single most common cause of hereditary homocystinuria, a
      multisystemic disease affecting to various extents the vasculature, connective
      tissues and central nervous system. At present, the crystal structure of CBS from
      Drosophila melanogaster is the only available structure of the full-length
      enzyme. Here we describe a cloning, overexpression, purification and preliminary
      crystallographic analysis of a full-length CBS from Apis mellifera (AmCBS) which
      maintains 51 and 46% sequence identity with its Drosophila and human homologs,
      respectively. The AmCBS yielded crystals belonging to space group P2(1)2(1)2(1),
      with unit-cell parameters a=85.90, b=95.87, c=180.33 A. Diffraction data were
      collected to a resolution of 3.0 A. The crystal structure contained two molecules
      in the asymmetric unit which presumably correspond to the dimeric species
      observed in solution.

PMID- 23143242
TI  - Purification, crystallization and preliminary X-ray diffraction analysis of an
      acidic phospholipase A2 with vasoconstrictor activity from Agkistrodon halys
      pallas venom.
AB  - Phospholipases A2 (PLA2s) are the major component of snake venoms and exert a
      variety of relevant toxic actions such as neurotoxicity and myotoxicity, amongst
      others. An acidic PLA2, here named AhV_aPA, was purified from Agkistrodon halys
      pallas venom by means of a three-step chromatographic procedure. AhV_aPA migrated
      as a single band on SDS-PAGE gels, with a molecular weight of about 14 kDa. Like
      other acidic aPLA2s, AhV_aPA has high enzymatic activity. Tension measurements of
      mouse thoracic aortic rings remarkably indicated that AhV_aPA could induce a
      further contractile response on the 60 mM K+-induced contraction, with an EC50 of
      369 nmol l(-1). Rod-shaped crystals were obtained by the hanging-drop vapour
      diffusion method and diffracted to a resolution limit of 2.30 A. The crystals
      belonged to space group P222, with unit-cell parameters a=44.27, b=68.39, c=81.54
      A.

PMID- 23143243
TI  - Purification, crystallization and preliminary X-ray crystallographic analysis of
      the ETS domain of human Ergp55 in complex with the cfos promoter DNA sequence.
AB  - The Ergp55 protein belongs to the Ets family of transciption factors. The Ets
      transcription factors are involved in various developmental processes and the
      regulation of cancer metabolism. They contain a highly similar DNA-binding domain
      known as the ETS domain and have diverse functions in oncogenesis and physiology.
      The Ets transcription factors differ in their DNA-binding preference at the ETS
      site and the mechanisms by which they target genes are not clearly understood. To
      understand its DNA-binding mechanism, the ETS domain of Ergp55 was expressed and
      purified. The ETS domain was crystallized in the native form and in complex forms
      with DNA sequences from the E74 and cfos promoters. An X-ray diffraction data set
      was collected from an ETS-cfos DNA complex crystal at a wavelength of 0.9725 A on
      the BM14 synchrotron beamline at the ESRF, France. The ETS-cfos DNA complex
      crystal belonged to space group C222(1), with four molecules in the asymmetric
      unit. For structure analysis, initial phases for the ETS-cfos DNA complex were
      obtained by the molecular-replacement technique with Phaser in the CCP4 suite
      using the coordinates of Fli-1 protein (PDB entry 1fli) and cfos DNA (PDB entry
      1bc7) as search models. Structure analysis of the ETS-cfos DNA complex may
      possibly explain the DNA-binding specificity and its mechanism of interaction
      with the ETS domain of Ergp55.

PMID- 23143244
TI  - Crystallization and preliminary crystallographic analysis of 2-aminophenol 1,6
      dioxygenase complexed with substrate and with an inhibitor.
AB  - Dioxygen activation implemented by nonhaem Fe(II) enzymes containing the 2-His-1
      carboxylate facial triad has been extensively studied in recent years. Extradiol
      dioxygenase is the archetypal member of this superfamily and catalyzes the
      oxygenolytic ring opening of catechol analogues. Here, the crystallization and
      preliminary X-ray analysis of 2-aminophenol 1,6-dioxygenase, an enzyme
      representing a minor subset of extradiol dioxygenases that catalyze the fission
      of 2-aminophenol rather than catecholic compounds, is reported. Crystals of the
      holoenzyme with FeII and of complexes with the substrate 2-aminophenol and the
      suicide inhibitor 4-nitrocatechol were grown using the cocrystallization method
      under the same conditions as used for the crystallization of the apoenzyme. The
      crystals belonged to space group C2 and diffracted to 2.3-2.7 A resolution; the
      crystal that diffracted to the highest resolution had unit-cell parameters
      a=270.24, b=48.39, c=108.55 A, beta=109.57 degrees . All X-ray data sets
      collected from diffraction-quality crystals were suitable for structure
      determination.

PMID- 23143245
TI  - Expression, purification, crystallization and preliminary X-ray diffraction
      analysis of the dihydroorotase domain of human CAD.
AB  - CAD is a 243 kDa eukaryotic multifunctional polypeptide that catalyzes the first
      three reactions of de novo pyrimidine biosynthesis: glutamine-dependent carbamyl
      phosphate synthetase, aspartate transcarbamylase and dihydroorotase (DHO). In
      prokaryotes, these activities are associated with monofunctional proteins, for
      which crystal structures are available. However, there is no detailed structural
      information on the full-length CAD protein or any of its functional domains apart
      from that it associates to form a homohexamer of ~1.5 MDa. Here, the expression,
      purification and crystallization of the DHO domain of human CAD are reported. The
      DHO domain forms homodimers in solution. Crystallization experiments yielded
      small crystals that were suitable for X-ray diffraction studies. A diffraction
      data set was collected to 1.75 A resolution using synchrotron radiation at the
      SLS, Villigen, Switzerland. The crystals belonged to the orthorhombic space group
      C222(1), with unit-cell parameters a=82.1, b=159.3, c=61.5 A. The Matthews
      coefficient calculation suggested the presence of one protein molecule per
      asymmetric unit, with a solvent content of 48%.

PMID- 23143246
TI  - Expression, purification, crystallization and preliminary X-ray crystallographic
      analysis of Zucchini from Drosophila melanogaster.
AB  - PIWI-interacting RNAs (piRNAs) bind PIWI proteins and silence transposons to
      maintain the genomic integrity of germ cells. Zucchini (Zuc), a phospholipase D
      superfamily member, is conserved among animals and is implicated in piRNA
      biogenesis. However, the underlying mechanism by which Zuc participates in piRNA
      biogenesis remains elusive. Drosophila melanogaster Zuc (DmZuc) was expressed in
      Escherichia coli, purified and crystallized. X-ray diffraction data were
      collected to 1.75 A resolution. The crystal belonged to space group P2(1), with
      unit-cell parameters a=55.0, b=71.2, c=56.3 A, beta=107.9 degrees .

PMID- 23143247
TI  - Cloning, purification and preliminary X-ray crystallographic analysis of the OmpA
      like domain of peptidoglycan-associated lipoprotein from Acinetobacter baumannii.
AB  - Peptidoglycan-associated lipoprotein (Pal) is one component of the Tol-Pal system
      that is involved in maintaining the integrity and stability of the outer
      membrane. The C-terminal OmpA-like domain of Pal interacts noncovalently with
      peptidoglycan. In this study, the OmpA-like domain of Pal from Acinetobacter
      baumannii was overexpressed in Escherichia coli strain BL21 (DE3), purified and
      crystallized using the vapour-diffusion method. A native crystal diffracted to
      1.4 A resolution and belonged to space group P6(1) or P6(5), with unit-cell
      parameters a=b=72.58, c=44.65 A, a calculated Matthews coefficient of 2.64 A3 Da(
      1) and one molecule per asymmetric unit.

PMID- 23143248
TI  - Cloning, purification and preliminary X-ray data analysis of the human ID2
      homodimer.
AB  - The ID proteins are named for their role as inhibitors of DNA binding and
      differentiation. They contain a helix-loop-helix (HLH) domain but lack a basic
      DNA-binding domain. In complex with basic HLH (bHLH) transcription factors, gene
      expression is regulated by DNA-binding inactivation. Although the HLH domain is
      highly conserved and shares a similar topology, the IDs preferentially bind class
      I bHLH-group members such as E47 (TCF3) but not the class III bHLH member Myc. A
      structure of an ID protein could potentially shed light on its mechanism. Owing
      to their short half-lives in vivo and reported in vitro instability, this paper
      describes the strategies that went into expressing sufficient soluble and stable
      ID2 to finally obtain diffraction-quality crystals. A 2.1 A resolution data set
      was collected from a crystal belonging to space group P3(1)21 with unit-cell
      parameters a=b=51.622, c=111.474 A, alpha=beta=90, gamma=120 degrees  that was
      obtained by hanging-drop vapour diffusion in a precipitant solution consisting of
      0.1 M MES pH 6.5, 2.0 M potassium acetate. The solvent content was consistent
      with the presence of one or two molecules in the asymmetric unit.

PMID- 23143249
TI  - Production and crystallization of a panel of structure-based mutants of the human
      myelin peripheral membrane protein P2.
AB  - The myelin sheath is a multilayered membrane that surrounds and insulates axons
      in the nervous system. One of the proteins specific to the peripheral nerve
      myelin is P2, a protein that is able to stack lipid bilayers. With the goal of
      obtaining detailed information on the structure-function relationship of P2, 14
      structure-based mutated variants of human P2 were generated and produced. The
      mutants were designed to potentially affect the binding of lipid bilayers by P2.
      All mutated variants were also crystallized and preliminary crystallographic data
      are presented. The structural data from the mutants will be combined with diverse
      functional assays in order to elucidate the fine details of P2 function at the
      molecular level.

PMID- 23143250
TI  - Crystallization, X-ray diffraction analysis and SIRAS phasing of human alpha-L
      iduronidase.
AB  - Human lysosomal alpha-L-iduronidase, whose deficiency causes
      mucopolysaccharidosis type I, was crystallized using sodium/potassium tartrate
      and polyethylene glycol 3350 as a precipitant. Using synchrotron radiation, a
      native data set was collected from a single crystal at 100 K to 2.3 A resolution.
      The crystal belonged to space group R3 with unit-cell dimensions of a=b=259.22,
      c=71.83 A. To obtain the phase information, mercury-derivative crystals were
      prepared and a single-wavelength anomalous dispersion (SAD) data set was
      collected at the Hg peak wavelength. Phase calculation with the single
      isomorphous replacement with anomalous scattering (SIRAS) method successfully
      yielded an interpretable electron-density map.

PMID- 23143251
TI  - Crystallization and X-ray diffraction studies of crustacean proliferating cell
      nuclear antigen.
AB  - Proliferating cell nuclear antigen (PCNA), a member of the sliding clamp family
      of proteins, interacts specifically with DNA replication and repair proteins
      through a small peptide motif called the PCNA-interacting protein or PIP box.
      PCNA is recognized as one of the key proteins involved in DNA metabolism. In the
      present study, the recombinant PCNA from Litopenaeus vannamei (LvPCNA) was
      heterologously overexpressed and purified using metal ion-affinity
      chromatography. Crystals suitable for diffraction grew overnight using the
      hanging-drop vapour-diffusion method. LvPCNA crystals belong to space group C2
      with unit-cell parameters a=144.6, b=83.4, c=74.3 A, beta=117.6 degrees . One
      data set was processed to 3 A resolution, with an overall Rmeas of 0.09 and a
      completeness of 93.3%. Initial phases were obtained by molecular replacement
      using a homology model of LvPCNA as the search model. Refinement and structural
      analysis are underway. This report is the first successful crystallographic
      analysis of a marine crustacean decapod shrimp (L. vannamei) proliferating cell
      nuclear antigen.

PMID- 23143252
TI  - Purification, crystallization, preliminary X-ray diffraction and molecular
      replacement studies of catfish (Clarias magur) haemoglobin.
AB  - Haemoglobin is an interesting physiologically significant protein composed of
      specific functional prosthetic haem and globin moieties. In recent decades, there
      has been substantial interest in attempting to understand the structural basis
      and functional diversity of fish haemoglobins (Hbs). Towards this end,
      purification, crystallization, preliminary X-ray diffraction and molecular
      replacement studies have been carried out on Clarias magur Hb. Crystals were
      grown by the hanging-drop vapour-diffusion method using PEG 2000 and NaCl as
      precipitants. The crystals belonged to the primitive monoclinic system P2, with
      unit-cell parameters a=98.35, b=56.63, c=112.88 A, beta=100.22 degrees ; a
      complete data set was collected to a resolution of 2.4 A. The Matthews
      coefficient of 2.42 A3 Da(-1) for the crystal indicated the presence of two
      alpha2beta2 tetramers in the asymmetric unit.

PMID- 23143253
TI  - Characterization, crystallization and preliminary X-ray diffraction analysis of
      an (S)-specific esterase (pfEstA) from Pseudomonas fluorescens KCTC 1767:
      enantioselectivity for potential industrial applications.
AB  - The structures and reaction mechanisms of enantioselective hydrolases, which can
      be used in industrial applications such as biotransformations, are largely
      unknown. Here, the X-ray crystallographic study of a novel (S)-specific esterase
      (pfEstA) from Pseudomonas fluorescens KCTC 1767, which can be used in the
      production of (S)-ketoprofen, is described. Multiple sequence alignments with
      other hydrolases revealed that pfEstA contains a conserved Ser67 within the S-X-X
      K motif as well as a highly conserved Tyr156. Recombinant protein containing an N
      terminal His tag was expressed in Escherichia coli, purified to homogeneity and
      characterized using SDS-PAGE, MALDI-TOF MS and enantioselective analysis. pfEstA
      was crystallized using a solution consisting of 1 M sodium citrate, 0.1 M CHES pH
      9.5, and X-ray diffraction data were collected to a resolution of 1.9 A with an
      Rmerge of 7.9%. The crystals of pfEstA belonged to space group P2(1)2(1)2(1),
      with unit-cell parameters a=65.31, b=82.13, c=100.41 A, alpha=beta=gamma=90
      degrees .

PMID- 23143254
TI  - Crystallization, optimization and preliminary X-ray characterization of a metal
      dependent PI-PLC from Streptomyces antibioticus.
AB  - A recombinant metal-dependent phosphatidylinositol-specific phospholipase C (PI
      PLC) from Streptomyces antibioticus has been crystallized by the hanging-drop
      method with and without heavy metals. The native crystals belonged to the
      orthorhombic space group P222, with unit-cell parameters a=41.26, b=51.86,
      c=154.78 A. The X-ray diffraction results showed significant differences in the
      crystal quality of samples soaked with heavy atoms. Additionally, drop pinning,
      which increases the surface area of the drops, was also used to improve crystal
      growth and quality. The combination of heavy-metal soaks and drop pinning was
      found to be critical for producing high-quality crystals that diffracted to 1.23
      A resolution.

PMID- 23143255
TI  - Crystallization of uridine phosphorylase from Shewanella oneidensis MR-1 in the
      laboratory and under microgravity and preliminary X-ray diffraction analysis.
AB  - Uridine phosphorylase (UDP, EC 2.4.2.3), a key enzyme in the pyrimidine salvage
      pathway, catalyses the reversible phosphorolysis of uridine to uracil and ribose
      1-phosphate. The gene expression of UDP from Shewanella oneidensis MR-1 was
      performed in the recipient strain Escherichia coli. The UDP protein was
      crystallized on earth (in the free form and in complex with uridine as the
      substrate) by the hanging-drop vapour-diffusion method at 296 K and under
      microgravity conditions (in the free form) aboard the Russian Segment of the
      International Space Station by the capillary counter-diffusion method. The data
      sets were collected to a resolution of 1.9 A from crystals of the free form grown
      on earth, 1.6 A from crystals of the complex with uridine and 0.95 A from
      crystals of the free form grown under microgravity. All crystals belong to the
      space group P2(1) and have similar unit-cell parameters. The crystal of uridine
      phosphorylase grown under microgravity diffracted to ultra-high resolution and
      gave high-quality X-ray diffraction data.

PMID- 23143256
TI  - Cloning, expression, purification, crystallization and preliminary X-ray
      crystallographic analyses of threonyl-tRNA synthetase editing domain from
      Aeropyrum pernix.
AB  - The proofreading function of aminoacyl-tRNA synthetases is crucial in maintaining
      the fidelity of protein synthesis. Most archaeal threonyl-tRNA synthetases
      (ThrRSs) possess a unique proofreading domain unrelated to their
      eukaryotic/bacterial counterpart. The crystal structure of this domain from the
      archaeon Pyrococcus abysii in complex with its cognate and noncognate substrate
      analogues had given insights into its catalytic and discriminatory mechanisms. To
      probe further into the mechanistic and evolutionary aspects of this domain, work
      has been extended to another archaeon Aeropyrum pernix. The organism possesses
      two proteins corresponding to threonyl-tRNA synthetase, i.e. ThrRS1 and ThrRS2,
      encoded by two different genes, thrS1 and thrS2, respectively. ThrRS1 is
      responsible for aminoacylation and ThrRS2 for proofreading activity. Here the
      purification, crystallization and preliminary X-ray crystallographic
      investigation of the N-terminal proofreading domain of ThrRS2 from A. pernix is
      reported. The crystals belong to either the P4(1)2(1)2 or P4(3)2(1)2 space group
      and consist of one monomer per asymmetric unit.

PMID- 23143257
TI  - Expression, purification, crystallization and preliminary X-ray structure
      analysis of Vibrio cholerae uridine phosphorylase in complex with thymidine.
AB  - A high-resolution structure of the complex of Vibrio cholerae uridine
      phosphorylase (VchUPh) with its physiological ligand thymidine is important in
      order to determine the mechanism of the substrate specificity of the enzyme and
      for the rational design of pharmacological modulators. Here, the expression and
      purification of VchUPh and the crystallization of its complex with thymidine are
      reported. Conditions for crystallization were determined with an automated
      Cartesian Dispensing System using The Classics, MbClass and MbClass II Suites
      crystallization kits. Crystals of the VchUPh-thymidine complex (of dimensions
      ~200-350 um) were grown by the sitting-drop vapour-diffusion method in ~7 d at
      291 K. The crystallization solution consisted of 1.5 ul VchUPh (15 mg ml(-1)), 1
      ul 0.1 M thymidine and 1.5 ul reservoir solution [15%(w/v) PEG 4000, 0.2 M
      MgCl(2).6H2O in 0.1 M Tris-HCl pH 8.5]. The crystals diffracted to 2.12 A
      resolution and belonged to space group P2(1) (No. 4), with unit-cell parameters
      a=91.80, b=95.91, c=91.89 A, beta=119.96 degrees . The Matthews coefficient was
      calculated as 2.18 A3 Da(-1); the corresponding solvent content was 43.74%.

PMID- 23143258
TI  - Crystallization and diffraction of an Isl1-Ldb1 complex.
AB  - A stable intramolecular complex comprising the LIM domains of the LIM-homeodomain
      protein Isl1 tethered to a peptide region of Ldb1 has been engineered, purified
      and crystallized. The orthorhombic crystals belonged to space group P222(1), with
      unit-cell parameters a=57.2, b=56.7, c=179.8 A, and diffracted to 3.10 A
      resolution.

PMID- 23143259
TI  - Crystallization and first data collection of the putative transfer protein TraN
      from the Gram-positive conjugative plasmid pIP501.
AB  - Conjugative plasmid transfer is the most important route for the spread of
      resistance and virulence genes among bacteria. Consequently, bacteria carrying
      conjugative plasmids are a substantial threat to human health, especially
      hospitalized patients. Whilst detailed information about the process has been
      obtained for Gram-negative type-4 secretion systems, little is known about the
      corresponding mechanisms in Gram-positive (G+) bacteria. The successful
      purification and crystallization of the putative transfer protein TraN from the
      G+ conjugative model plasmid pIP501 of Enterococcus faecalis are presented.
      Native crystals diffracted to 1.8 A resolution on a synchrotron beamline. The
      crystals belonged to space group P2(1), with unit-cell parameters a=32.88,
      b=54.94, c=57.71 A, beta=91.89 degrees  and two molecules per asymmetric unit.

PMID- 23143260
TI  - Purification, crystallization and preliminary X-ray diffraction studies of the
      ATP-binding subunit of an ABC transporter from Geobacillus kaustophilus.
AB  - ATP-binding cassette (ABC) transporters, also known as traffic ATPases, form a
      large family of integral membrane proteins responsible for the translocation of a
      variety of chemically diverse substrates across the lipid bilayers of cellular
      membranes of both prokaryotes and eukaryotes by the hydrolysis of ATP. The ATP
      binding subunit of an ABC transporter from Geobacillus kaustophilus, a
      homodimeric enzyme, was overexpressed in Escherichia coli and purified. Crystals
      were obtained using the microbatch-under-oil method at 291 K. X-ray diffraction
      data to 1.6 A resolution were collected on SPring-8 beamline BL26B1. The crystals
      belonged to the orthorhombic space group I222, with unit-cell parameters a=54.94,
      b=78.63, c=112.96 A. Assuming the presence of a dimer in the asymmetric unit gave
      a crystal volume per protein weight (VM) of 2.32 A3 Da(-1) and a solvent content
      of 47%; this was consistent with the results of a dynamic light-scattering
      experiment, which showed a dimeric state of the protein in solution. Molecular
      replacement trials using the crystal structure of HisP from the Salmonella
      typhimurium ATP-binding subunit of an ABC transporter as a search model did not
      provide a satisfactory solution, indicating that the two ATP-binding subunits of
      ABC transporters have substantially different structures.

PMID- 23143261
TI  - Ellman's reagent in promoting crystallization and structure determination of
      Anabaena CcbP.
AB  - Obtaining crystals presented a bottleneck in the structural study of Anabaena
      cyanobacterial Ca2+-binding protein (CcbP). In this report, the promoting effect
      of Ellman's reagent [5,5'-dithiobis(2-nitrobenzoic acid); DTNB] on the
      crystallization of CcbP is described. CcbP contains one free cysteine. A quick
      and simple oxidation reaction with DTNB blocked the free cysteine in purified
      CcbP and generated a homogenous monomeric protein for crystallization. The
      crystal structure of DTNB-modified CcbP was determined by the single-wavelength
      anomalous diffraction method. Structure analysis indicated that DTNB modification
      facilitated crystallization of CcbP by inducing polar interactions in the crystal
      lattice. DTNB-mediated cysteine modification was demonstrated to have little
      effect on the overall structure and the Ca2+ binding of CcbP. Thus, DTNB
      modification may provide a simple and general approach for protein modification
      to improve the success of crystallization screening.

PMID- 23143265
TI  - Cloning, expression, crystallization and preliminary X-ray crystallographic
      analysis of aspartyl aminopeptidase from the apeB gene of Pseudomonas aeruginosa.
      Retraction.
AB  - The article by Natarajan & Mathews [(2012) Acta Cryst. F68, 207-210] is
      retracted.

PMID- 23143266
TI  - Recovering ensembles of chromatin conformations from contact probabilities.
AB  - The 3D higher order organization of chromatin within the nucleus of eukaryotic
      cells has so far remained elusive. A wealth of relevant information, however, is
      increasingly becoming available from chromosome conformation capture (3C) and
      related experimental techniques, which measure the probabilities of contact
      between large numbers of genomic sites in fixed cells. Such contact probabilities
      (CPs) can in principle be used to deduce the 3D spatial organization of
      chromatin. Here, we propose a computational method to recover an ensemble of
      chromatin conformations consistent with a set of given CPs. Compared with
      existing alternatives, this method does not require conversion of CPs to mean
      spatial distances. Instead, we estimate CPs by simulating a physically realistic,
      bead-chain polymer model of the 30-nm chromatin fiber. We then use an approach
      from adaptive filter theory to iteratively adjust the parameters of this polymer
      model until the estimated CPs match the given CPs. We have validated this method
      against reference data sets obtained from simulations of test systems with up to
      45 beads and 4 loops. With additional testing against experiments and with
      further algorithmic refinements, our approach could become a valuable tool for
      researchers examining the higher order organization of chromatin.

PMID- 23143267
TI  - The RNA helicase DDX5/p68 is a key factor promoting c-fos expression at different
      levels from transcription to mRNA export.
AB  - It is widely accepted that pre-mRNA maturation, including splicing, is tightly
      coupled to both transcription and mRNA export, but factors linking the three
      processes are less understood. By analysing the estrogen-regulated expression of
      the c-fos mRNA that is processed during transcription, we show that the ddx5 RNA
      helicase, is required throughout the major nuclear steps of the expression of the
      c-fos gene, from transcription to mRNA export. Indeed, ddx5, whose recruitment on
      the c-fos gene was increased upon estrogen treatment, was required for the full
      transcriptional activation of the c-fos gene. In addition, ddx5 was required for
      c-fos co-transcriptional RNA splicing. When splicing occurred post
      transcriptionally in the absence of ddx5, the c-fos mRNA was poorly exported into
      the cytosol because of inefficient recruitment of the TAP mRNA export receptor.
      Finally, ddx5 was present in the c-fos messenger ribonucleoprotein together with
      mRNA export factors, which further supports that ddx5 is a key operator in the c
      fos 'mRNA factory'.

PMID- 23143268
TI  - A multi-parametric flow cytometric assay to analyze DNA-protein interactions.
AB  - Interactions between DNA and transcription factors (TFs) guide cellular function
      and development, yet the complexities of gene regulation are still far from being
      understood. Such understanding is limited by a paucity of techniques with which
      to probe DNA-protein interactions. We have devised magnetic protein
      immobilization on enhancer DNA (MagPIE), a simple, rapid, multi-parametric assay
      using flow cytometric immunofluorescence to reveal interactions among TFs,
      chromatin structure and DNA. In MagPIE, synthesized DNA is bound to magnetic
      beads, which are then incubated with nuclear lysate, permitting sequence-specific
      binding by TFs, histones and methylation by native lysate factors that can be
      optionally inhibited with small molecules. Lysate protein-DNA binding is
      monitored by flow cytometric immunofluorescence, which allows for accurate
      comparative measurement of TF-DNA affinity. Combinatorial fluorescent staining
      allows simultaneous analysis of sequence-specific TF-DNA interaction and
      chromatin modification. MagPIE provides a simple and robust method to analyze
      complex epigenetic interactions in vitro.

PMID- 23143269
TI  - SynSysNet: integration of experimental data on synaptic protein-protein
      interactions with drug-target relations.
AB  - We created SynSysNet, available online at
      http://bioinformatics.charite.de/synsysnet, to provide a platform that creates a
      comprehensive 4D network of synaptic interactions. Neuronal synapses are
      fundamental structures linking nerve cells in the brain and they are responsible
      for neuronal communication and information processing. These processes are
      dynamically regulated by a network of proteins. New developments in interaction
      proteomics and yeast two-hybrid methods allow unbiased detection of interactors.
      The consolidation of data from different resources and methods is important to
      understand the relation to human behaviour and disease and to identify new
      therapeutic approaches. To this end, we established SynSysNet from a set of ~1000
      synapse specific proteins, their structures and small-molecule interactions. For
      two-thirds of these, 3D structures are provided (from Protein Data Bank and
      homology modelling). Drug-target interactions for 750 approved drugs and 50 000
      compounds, as well as 5000 experimentally validated protein-protein interactions,
      are included. The resulting interaction network and user-selected parts can be
      viewed interactively and exported in XGMML. Approximately 200 involved pathways
      can be explored regarding drug-target interactions. Homology-modelled structures
      are downloadable in Protein Data Bank format, and drugs are available as MOL
      files. Protein-protein interactions and drug-target interactions can be viewed as
      networks; corresponding PubMed IDs or sources are given.

PMID- 23143270
TI  - The ConsensusPathDB interaction database: 2013 update.
AB  - Knowledge of the various interactions between molecules in the cell is crucial
      for understanding cellular processes in health and disease. Currently available
      interaction databases, being largely complementary to each other, must be
      integrated to obtain a comprehensive global map of the different types of
      interactions. We have previously reported the development of an integrative
      interaction database called ConsensusPathDB (http://ConsensusPathDB.org) that
      aims to fulfill this task. In this update article, we report its significant
      progress in terms of interaction content and web interface tools. ConsensusPathDB
      has grown mainly due to the integration of 12 further databases; it now contains
      215 541 unique interactions and 4601 pathways from overall 30 databases. Binary
      protein interactions are scored with our confidence assessment tool, IntScore.
      The ConsensusPathDB web interface allows users to take advantage of these
      integrated interaction and pathway data in different contexts. Recent
      developments include pathway analysis of metabolite lists, visualization of
      functional gene/metabolite sets as overlap graphs, gene set analysis based on
      protein complexes and induced network modules analysis that connects a list of
      genes through various interaction types. To facilitate the interactive, visual
      interpretation of interaction and pathway data, we have re-implemented the graph
      visualization feature of ConsensusPathDB using the Cytoscape.js library.

PMID- 23143272
TI  - Mammalian cells acquire epigenetic hallmarks of human cancer during
      immortalization.
AB  - Progression to malignancy requires that cells overcome senescence and switch to
      an immortal phenotype. Thus, exploring the genetic and epigenetic changes that
      occur during senescence/immortalization may help elucidate crucial events that
      lead to cell transformation. In the present study, we have globally profiled DNA
      methylation in relation to gene expression in primary, senescent and immortalized
      mouse embryonic fibroblasts. Using a high-resolution genome-wide mapping
      technique, followed by extensive locus-specific validation assays, we have
      identified 24 CpG islands that display significantly higher levels of CpG
      methylation in immortalized cell lines as compared to primary murine fibroblasts.
      Several of these hypermethylated CpG islands are associated with genes involved
      in the MEK-ERK pathway, one of the most frequently disrupted pathways in cancer.
      Approximately half of the hypermethylated targets are developmental regulators,
      and bind to the repressive Polycomb group (PcG) proteins, often in the context of
      bivalent chromatin in mouse embryonic stem cells. Because PcG-associated aberrant
      DNA methylation is a hallmark of several human malignancies, our methylation data
      suggest that epigenetic reprogramming of pluripotency genes may initiate cell
      immortalization. Consistent with methylome alterations, global gene expression
      analysis reveals that the vast majority of genes dysregulated during cell
      immortalization belongs to gene families that converge into the MEK-ERK pathway.
      Additionally, several dysregulated members of the MAP kinase network show
      concomitant hypermethylation of CpG islands. Unlocking alternative epigenetic
      routes for cell immortalization will be paramount for understanding crucial
      events leading to cell transformation. Unlike genetic alterations, epigenetic
      changes are reversible events, and as such, can be amenable to pharmacological
      interventions, which makes them appealing targets for cancer therapy when genetic
      approaches prove inadequate.

PMID- 23143271
TI  - A dynamic and intricate regulatory network determines Pseudomonas aeruginosa
      virulence.
AB  - Pseudomonas aeruginosa is a metabolically versatile bacterium that is found in a
      wide range of biotic and abiotic habitats. It is a major human opportunistic
      pathogen causing numerous acute and chronic infections. The critical traits
      contributing to the pathogenic potential of P. aeruginosa are the production of a
      myriad of virulence factors, formation of biofilms and antibiotic resistance.
      Expression of these traits is under stringent regulation, and it responds to
      largely unidentified environmental signals. This review is focused on providing a
      global picture of virulence gene regulation in P. aeruginosa. In addition to key
      regulatory pathways that control the transition from acute to chronic infection
      phenotypes, some regulators have been identified that modulate multiple virulence
      mechanisms. Despite of a propensity for chaotic behaviour, no chaotic motifs were
      readily observed in the P. aeruginosa virulence regulatory network. Having a
      'birds-eye' view of the regulatory cascades provides the forum opportunities to
      pose questions, formulate hypotheses and evaluate theories in elucidating P.
      aeruginosa pathogenesis. Understanding the mechanisms involved in making P.
      aeruginosa a successful pathogen is essential in helping devise control
      strategies.

PMID- 23143273
TI  - What is the best timing of surgery in patients with post-infarct ventricular
      septal rupture?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was 'in which patients with a post-infarct
      ventricular septal rupture (PIVSR) might immediate surgery give better results
      than delayed surgery in terms of mortality'? Altogether, 88 papers were found
      using the reported search criteria, of which 6 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 recommendations are based on outcomes from 3238
      patients undergoing surgery for PIVSR. Mean age was 67.5 +/- 8.8 (40-88 years).
      Left ventricular function was compromised in most patients with mean ejection
      fraction of 40%. All papers carried out univariate and/or multivariate analyses
      of variables that contributed to different in-hospital mortalities. Early
      surgery, i.e. from >3 days to within 4 weeks after MI, had an overall in-hospital
      mortality of 52.4%; delayed surgery, typically from 1 week to after 4 weeks post
      myocardial infarction, had an overall operative in-hospital mortality of 7.56%.
      Most authors observe that a shorter time between rupture and surgery is an
      unfavourable predictor of outcome independent of haemodynamic status. The
      consensus was that nearly all patients with PIVSR, particularly if >15 mm
      diameter with a significant shunt and resultant haemodynamic deterioration,
      should undergo early surgical repair. The precise timing of surgery depends on
      patients' haemodynamic status. Exclusion from surgery should be considered if
      life expectancy or quality is severely limited by another limiting underlying
      pathology. If the patient is in cardiogenic shock, due to pulmonary to systemic
      blood flow ratio shunt rather than infarct size, immediate surgery should follow
      resuscitation measures and cardiac support. If the patient is haemodynamically
      stable, surgery could be performed after 3-4 weeks of medical optimization with
      inotropic and mechanical cardiac support. If there is clinical deterioration,
      immediate surgery is indicated.

PMID- 23143274
TI  - Transcriptional repression of the APC/C activator CCS52A1 promotes active
      termination of cell growth.
AB  - Spatial and temporal control of cell growth is central for the morphogenesis of
      multicellular organisms. For some cell types that undergo extensive post-mitotic
      cell growth, such as neurons and hair cells, orchestrating the extent of post
      mitotic cell growth with development is vital for their physiology and function.
      Previous studies suggested that the extent of cell growth is linked with an
      increase in ploidy by endoreduplication but how developmental signals control
      endocycling and cell growth is not understood in both animals and plants. In this
      study we show that a trihelix transcription factor, GT2-LIKE 1 (GTL1), actively
      terminates ploidy-dependent cell growth and its developmentally regulated
      expression is one of the key determinants of cell size in Arabidopsis leaf hair
      cells (trichomes). Through genome-wide chromatin-binding studies (ChIP-chip)
      coupled with transcriptional profiling, we further demonstrate that GTL1 directly
      represses the transcription of CDH1/FZR/CCS52, an activator of the anaphase
      promoting complex/cyclosome (APC/C), to stop the endocycle progression and ploidy
      dependent cell growth. Thus, our findings uncover a previously uncharacterised
      key molecular link between developmental programming and cell-size control,
      highlighting the central role of APC/C in post-mitotic cell growth.

PMID- 23143275
TI  - Source identification of soil mercury in the Spanish islands.
AB  - This study spatially analysed the relation between mercury (Hg) content in soil
      and Hg in rock fragment for the purpose of assessing natural soil Hg contribution
      compared with Hg from human inputs. We present the Hg content of 318 soil and
      rock fragment samples from 11 islands distributed into two Spanish archipelagos
      (the volcanic Canary Islands [Canaries] and the Mediterranean Balearic [Balearic]
      islands). Assumedly both are located far enough away from continental Hg sources
      to be able to minimise the effects of diffuse pollution. Physical and chemical
      soil properties were also specified for the samples. Hg contents were
      significantly greater in the Balearic limestone soils (61 MUg kg(-1)) than in the
      volcanic soils of the Canaries (33 MUg kg(-1)). Hg levels were also greater in
      topsoil than in rocky fragments, especially on the Balearics. The soil-to-rock
      ratios varied between 1 and 30. Interestingly, the highest topsoil-to-rock Hg
      ratio (>16 *) was found in the vicinity of a coal-fired power plant in Majorca,
      whereas no similar areas in the Canary archipelago were identified.

PMID- 23143276
TI  - The influence of DOC trends on light climate and periphyton biomass in the Ganga
      River, Varanasi, India.
AB  - Investigations on periphyton along an eutrophication gradient (NO(3)(-) = 0.23
      0.96 mg L(-1); PO(4)(-3) = 0.16-0.86 mg L(-1)) of Ganga River indicated that
      benthic algal biomass decreased with increasing concentrations of nutrients and
      dissolved organic carbon (DOC). Periphyton biomass showed negative relationship
      (R(2) = 0.98; p < 0.0001) with DOC and positive relationship (R(2) = 0.96; p <
      0.0001) with Secchi depth. Sites with high DOC showed dominance of cyanophycean
      Phormidium uncinatum. The study shows that the rising concentration of DOC over
      time may alter the light climate and consequently the fate of benthic primary
      producers in Ganga River.

PMID- 23143277
TI  - Potential risk assessment of trace elements and PAHs in sediment samples of the
      Ebro River basin (Spain).
AB  - This study was carried out in order to assess potential toxicity of hazardous
      pollutants (8 trace elements and 8 polycyclic aromatic hydrocarbons) in 20
      sediment samples of the Ebro River basin (Spain) sampled in 2009. Mean-probable
      effect concentration quotient (m-PECQ) was found to range from 0.03 to 0.79. Two
      sites were classified as high priority sites in order to take future remediation
      actions due to their high m-PECQ value (>0.5). Worst-case scenario in equilibrium
      partitioning approach showed that acid volatile sulfide (AVS) content was greater
      than total trace element concentration in all samples. However, 4 sediments were
      classified as degraded due to the high AVS content measured (>50 mmol/kg).
      Principal component analysis classified the samples according to similar chemical
      characteristics and revealed that industrial activities are the main source of
      pollution of the basin.

PMID- 23143278
TI  - Rapid prediction of multi-dimensional NMR data sets.
AB  - We present a computational environment for Fast Analysis of multidimensional NMR
      DAta Sets (FANDAS) that allows assembling multidimensional data sets from a
      variety of input parameters and facilitates comparing and modifying such "in
      silico" data sets during the various stages of the NMR data analysis. The input
      parameters can vary from (partial) NMR assignments directly obtained from
      experiments to values retrieved from in silico prediction programs. The resulting
      predicted data sets enable a rapid evaluation of sample labeling in light of
      spectral resolution and structural content, using standard NMR software such as
      Sparky. In addition, direct comparison to experimental data sets can be used to
      validate NMR assignments, distinguish different molecular components, refine
      structural models or other parameters derived from NMR data. The method is
      demonstrated in the context of solid-state NMR data obtained for the cyclic
      nucleotide binding domain of a bacterial cyclic nucleotide-gated channel and on
      membrane-embedded sensory rhodopsin II. FANDAS is freely available as web portal
      under WeNMR ( http://www.wenmr.eu/services/FANDAS ).

PMID- 23143279
TI  - A study on the influence of fast amide exchange on the accuracy of (15)N
      relaxation rate constants.
AB  - (15)N relaxation rates of amide moieties provide insight both into global as well
      as local backbone dynamics of peptides and proteins. As the differences in the
      relaxation rates in general are small, their accurate determination is of prime
      importance. One potential source of error is fast amide exchange. It is well
      known that in its presence the effects of saturation transfer and H/D exchange
      may result in erroneous apparent relaxation rates R (1) and R (2). Here, the
      extent of these errors is rigorously examined. Theoretical considerations reveal
      that even when saturation effects are absent, H/D exchange will easily result in
      significant deviations from the true values. In particular overestimations of up
      to 10 % in R (1) and up to 5 % in R (2) are observed. An alternative scheme for
      fitting the relaxation data to the corresponding exponentials is presented that
      in the best cases not only delivers more accurate relaxation rates but also
      allows extracting estimates for the exchange rates. The theoretical computations
      were tested and verified for the case of ubiquitin.

PMID- 23143280
TI  - Nationwide surveillance of antimicrobial susceptibility patterns of pathogens
      isolated from surgical site infections (SSI) in Japan.
AB  - To investigate the trends of antimicrobial resistance in pathogens isolated from
      surgical site infections (SSI), a Japanese surveillance committee conducted the
      first nationwide survey. Seven main organisms were collected from SSI at 27
      medical centers in 2010 and were shipped to a central laboratory for
      antimicrobial susceptibility testing. A total of 702 isolates from 586 patients
      with SSI were included. Staphylococcus aureus (20.4 %) and Enterococcus faecalis
      (19.5 %) were the most common isolates, followed by Pseudomonas aeruginosa (15.4
      %) and Bacteroides fragilis group (15.4 %). Methicillin-resistant S. aureus among
      S. aureus was 72.0 %. Vancomycin MIC 2 MUg/ml strains accounted for 9.7 %. In
      Escherichia coli, 11 of 95 strains produced extended-spectrum beta-lactamase
      (Klebsiella pneumoniae, 0/53 strains). Of E. coli strains, 8.4 % were resistant
      to ceftazidime (CAZ) and 26.3 % to ciprofloxacin (CPFX). No P. aeruginosa strains
      produced metallo-beta-lactamase. In P. aeruginosa, the resistance rates were 7.4
      % to tazobactam/piperacillin (TAZ/PIPC), 10.2 % to imipenem (IPM), 2.8 % to
      meropenem, cefepime, and CPFX, and 0 % to gentamicin. In the B. fragilis group,
      the rates were 28.6 % to clindamycin, 5.7 % to cefmetazole, 2.9 % to TAZ/PIPC and
      IPM, and 0 % to metronidazole (Bacteroides thetaiotaomicron; 59.1, 36.4, 0, 0, 0
      %). MIC90 of P. aeruginosa isolated 15 days or later after surgery rose in
      TAZ/PIPC, CAZ, IPM, and CPFX. In patients with American Society of
      Anesthesiologists (ASA) score >=3, the resistance rates of P. aeruginosa to
      TAZ/PIPC and CAZ were higher than in patients with ASA <=2. The data obtained in
      this study revealed the trend of the spread of resistance among common species
      that cause SSI. Timing of isolation from surgery and the patient's physical
      status affected the selection of resistant organisms.

PMID- 23143281
TI  - The dynactin p150 subunit: cell biology studies of sequence changes found in
      ALS/MND and Parkinsonian syndromes.
AB  - The dynactin p150glued subunit, encoded by the gene DCTN1 is part of the dynein
      dynactin motor protein complex responsible for retrograde axonal transport. This
      subunit is a candidate modifier for neurodegenerative diseases, in particular
      motoneuron and extrapyramidal diseases. Based on an extensive screening effort of
      all 32 exons in more than 2,500 ALS/MND patients, patients suffering from
      Parkinsonian Syndromes and controls, we investigated 24 sequence variants of p150
      in cell-based studies. We used both non-neuronal cell lines and primary rodent
      spinal motoneurons and report on cell biological abnormalities in five of these
      sequence alterations and also briefly report on the clinical features. Our
      results suggest the presence of biological changes caused by some p150 mutants
      pointing to a potential pathogenetic significance as modifier of the phenotype of
      the human disease.

PMID- 23143282
TI  - Synthesis, spectral, and structural characterizations of imidazole oxalato
      molybdenum(IV/V/VI) complexes.
AB  - Substitutions of trans-Na(Him)[Mo(2)O(4)(ox)(2)(H(2)O)(2)].H(2)O (1) and trans
      (Him)(2)[Mo(2)O(4)(ox)(2)(H(2)O)(2)] (2) with imidazole result in the formation
      of the mixed-ligand molybdenum complexes cis
      Na(2)[Mo(2)O(4)(ox)(2)(im)(2)].4.5H(2)O (3), cis
      K(2)[Mo(2)O(4)(ox)(2)(im)(2)].3H(2)O (4), respectively (H(2)ox = oxalic acid; im
      = imidazole). Further reduction of cis-K(2)[Mo(2)O(4)(ox)(2)(im)(2)].3H(2)O (4)
      gives a trinuclear molybdenum(IV) complex K(Him)[Mo(3)O(4)(ox)(3)(im)(3)].3H(2)O
      (5), which contains an incomplete cubane cluster [Mo(IV)(3)O(4)](4+). Two novel
      trinuclear mixed-valence imidazole compounds [Mo(3)O(8)(im)(4)](im).H(2)O (6) and
      [Mo(3)O(8)(im)(4)].H(2)O (7) were obtained by the reduction of
      (Him)(4)[Mo(8)O(26)(im)(2)] (8). Both 6 and 7 contain a novel
      Mo(VI)O(4)(Mo(V)(2)O(4)) center, where the [Mo(V)(2)O(4)](2+) unit is linked by
      [Mo(VI)O(4)](2-) anion. The Mo-Mo bond distances in 1-7 decrease with the
      decrease of oxidation state of molybdenum. Solid and solution NMR spectra show
      that imidazole molybdenum compounds 6-8 fully dissociate in solution, where
      solvated imidazole and imidazolium groups in 6 and 8 could be served as internal
      references in their solid (13)C NMR spectra. Furthermore, mixed-ligand molybdenum
      species 3 and 4 are stable in water. Stabilities of 3 and 4 in solution may be
      attributed to the strong coordination of bidentate oxalate and the formation of
      hydrogen bond. Dimers 2 and 4 display quasi-reversible redox process, while
      trimer 6 is irreversible. Bond valence calculations for 1-8 are consistent with
      their oxidation states of molybdenum atoms. Calculation of the oxidation state in
      recent structure of iron molybdenum cofactor [MoFe(7)S(9)C(R-homocit)] (FeMo-co)
      is 3.318.

PMID- 23143283
TI  - A cost effectiveness study of eribulin versus standard single-agent cytotoxic
      chemotherapy for women with previously treated metastatic breast cancer.
AB  - Eribulin was FDA approved in 2012 as a treatment for patients with MBC who have
      previously received at least two prior chemotherapy regimens. The aim of this
      analysis was to assess the cost effectiveness of eribulin versus the three most
      commonly utilized drugs (TPC) in the EMBRACE trial: vinorelbine, gemcitabine, and
      capecitabine (X); and to other branded FDA approved drugs: ixabepilone (I),
      liposomal-doxorubicin (D), and nab-paclitaxel. We created a decision-analytical
      and a Markov model using clinical data from the EMBRACE trial. Health utilities
      were derived from the published literature. Costs for drug acquisition, physician
      visits, and laboratory tests were obtained from Medicare Services Drug Payment
      Table and Physician Fee Schedule and are represented in 2012 USD. Life-years
      saved (LY), quality-adjusted life years (QALY), and incremental cost
      effectiveness ratio (ICER) were calculated. Eribulin added 0.208 LY and 0.119
      QALY with an incremental cost over TPC of $25,458, and therefore an ICER of
      $213,742 per QALY. The main drivers of the model were drug cost, PFS, OS, and
      health utility values. The results of the model were robust in sensitivity
      analyses. Relative to I, D, A, and X, the ICER for eribulin was $76,823,
      $109,283, $129,773, and $167,267, respectively. Even with a more contemporary
      willingness-to-pay threshold of approximately $120,000 per QALY, eribulin was not
      found to be cost effective in the treatment of MBC relative to TPC; relative to
      some more expensive branded drugs, eribulin appears to be cost effective.

PMID- 23143284
TI  - Preoperative systemic therapy in locoregional management of early breast cancer:
      highlights from the Kyoto Breast Cancer Consensus Conference.
AB  - Data reviewed at the Kyoto Breast Cancer Consensus Conference (KBCCC) showed that
      preoperative systemic therapy (PST) could optimize surgery through the
      utilization of information relating to pre- and post-PST tumor stage, therapeutic
      sensitivity, and treatment-induced changes in the biological characteristics of
      the tumor. As such, it was noted that the biological characteristics of the
      tumor, such as hormone receptors, human epidermal growth factor receptor-2,
      histological grade, cell proliferative activity, mainly defined by the Ki67
      labeling index, and the tumor's multi-gene signature, should be considered in the
      planning of both systemic and local therapy. Furthermore, the timing of axillary
      sentinel lymph node diagnosis (i.e., before or after the PST) was also noted to
      be critical in that it may influence the likelihood of axillary preservation,
      even in node positive cases. In addition, axillary diagnosis with ultrasound and
      concomitant fine needle aspiration cytology or core needle biopsy (CNB) was
      reported to contribute to the construction of a treatment algorithm for patient
      specific or individualized axillary surgery. Following PST, planning for breast
      surgery should therefore be based on tumor subtype, tumor volume and extent,
      therapeutic response to PST, and patient preference. Nomograms for predicting
      nodal status and drug sensitivity were also recognized as a tool to support
      decision-making in the selection of surgical treatment. Overall, review of data
      at the KBCCC showed that PST increases the likelihood of patients receiving
      localized surgery and individualized treatment regimens.

PMID- 23143285
TI  - The expression of ABC efflux pump, Rv1217c-Rv1218c, and its association with
      multidrug resistance of Mycobacterium tuberculosis in China.
AB  - Currently the treatment of Mycobacterium tuberculosis (TB) infection is largely
      limited due to the prevalence of multidrug resistance strains. Over-expressing
      the efflux pumps such as the ATP-binding cassette (ABC) transporter has been
      reported to significantly contribute to its resistance to several antibiotics.
      This study investigated the expression profile of one important ABC efflux pump,
      Rv1217c-Rv1218c, by quantitative real-time PCR (RT-qPCR) in clinical isolates
      from China, which also revealed its association with the multidrug resistance of
      M. tuberculosis. Significantly increased expressions of Rv1217c and Rv1218c at
      transcriptional level have been observed in multidrug-resistant TB group (MDR-TB)
      compared to those of the drug-susceptible group (P < 0.05), when H37Rv strain was
      used as the control. Furthermore, correlation analysis revealed that the over
      expression of both Rv1217c and Rv1218c resulted in the higher minimum inhibition
      concentrations (MICs) of rifampicin (RIF) (OR = 1.01, P < 0.05 of Rv1217c; OR =
      1.23, P < 0.05 of Rv1218c), while the over-expression of Rv1218c only led to the
      higher MICs of isoniazid (INH) (OR = 1.17, P < 0.05). Our findings contributed to
      the better understanding of the molecular mechanisms of ABC efflux pumps, in
      particular Rv1217c-Rv1218c, in M. tuberculosis and will assist in developing new
      antibiotic treatments for multidrug-resistant M. tuberculosis in the future.

PMID- 23143286
TI  - Variability of bacterial community composition on leaves between and within plant
      species.
AB  - The phyllosphere is one of the largest habitats for terrestrial microorganisms.
      To gain a better insight into the factors underlying the composition of bacterial
      communities inhabiting leaf surfaces we performed culture-dependent and
      independent (Denaturing Gradient Gel Electrophoresis) analyses on the bacteria
      associated with the leaves of three plant species: Amygdalus communis, Citrus
      paradisi, and Nicotiana glauca. We found that the culturable classes Bacilli and
      Actinobacteria were the predominant classes on the phyllosphere of all three
      plant species. In contrast to this consistency on the bacterial class level, we
      found a significant variation on the bacterial species-level based on the
      culturable methods. Although some variation was detected among individual plants
      within one plant species, the inter-specific variability exceeded the intra
      specific variability. C. paradisi leaf surface had the highest predicted total
      species richness (Chao 2 and ICE) and the highest species diversity (betaw) among
      the three plant species. Our findings demonstrate that environmental conditions,
      mainly the plant species within a site, govern the bacterial community
      composition on leaf surfaces.

PMID- 23143287
TI  - Filamentous fungi transported by birds during migration across the mediterranean
      sea.
AB  - The potential for the transport and diffusion of some pathogenic microorganisms
      by migratory birds is of concern. Migratory birds may be involved in the
      dispersal of microorganisms and may play a role of mechanical and biological
      vectors. The efficiency of dispersal of pathogenic microorganisms depends on a
      wide range of biotic and abiotic factors that influence the survival or
      disappearance of a given agent in a geographical area. In the present study, 349
      migratory birds were captured in four sites (Mazara del Vallo, Lampedusa, Ustica
      and Linosa), representing the main stop-over points during spring and autumnal
      migration, and analyzed for the presence of filamentous fungi. A total of 2,337
      filamentous fungi were isolated from 216 birds and identified by a combined
      phenotypic-genotypic approach to species level. Twelve species were identified in
      the study, with Cladosporium cladosporioides, Alternaria alternata, and
      Aspergillus niger as the most abundant. The transport of these fungal species
      isolated in this study is of considerable importance because some of these
      species can create dangers to human health.

PMID- 23143288
TI  - Isolation and characterization of antagonistic Bacillus strains capable to
      degrade ethylenethiourea.
AB  - In this study, more than 150 bacteria showing antagonistic properties against
      bacterial and fungal pathogens of the tomato plant were isolated and
      characterized. The most efficient agents against these phytopathogenic
      microorganisms belong to the genus Bacillus: the best biocontrol isolates were
      representatives of Bacillus subtilis, B. mojavensis and B. amyloliquefaciens
      species. They intensively produced fengycin or/and surfactin depsipeptide
      antibiotics and also proved to be excellent protease secretors. It was proved,
      that the selected strains were able to use ethylenethiourea (ETU) as sole
      nitrogen source. These antagonistic and ETU-degrading Bacillus strains can be
      applied as biocontrol and also as bioremediation agents.

PMID- 23143289
TI  - Isolation and characterisation of lytic bacteriophages of Klebsiella pneumoniae
      and Klebsiella oxytoca.
AB  - Klebsiella bacteria have emerged as an increasingly important cause of community
      acquired nosocomial infections. Extensive use of broad-spectrum antibiotics in
      hospitalised patients has led to both increased carriage of Klebsiella and the
      development of multidrug-resistant strains that frequently produce extended
      spectrum beta-lactamases and/or other defences against antibiotics. Many of these
      strains are highly virulent and exhibit a strong propensity to spread. In this
      study, six lytic Klebsiella bacteriophages were isolated from sewage-contaminated
      river water in Georgia and characterised as phage therapy candidates. Two of the
      phages were investigated in greater detail. Biological properties, including
      phage morphology, nucleic acid composition, host range, growth phenotype, and
      thermal and pH stability were studied for all six phages. Limited sample
      sequencing was performed to define the phylogeny of the K. pneumoniae- and K.
      oxytoca-specific bacteriophages vB_Klp_5 and vB_Klox_2, respectively. Both of the
      latter phages had large burst sizes, efficient rates of adsorption and were
      stable under different adverse conditions. Phages reported in this study are
      double-stranded DNA bacterial viruses belonging to the families Podoviridae and
      Siphoviridae. One or more of the six phages was capable of efficiently lysing ~63
      % of Klebsiella strains comprising a collection of 123 clinical isolates from
      Georgia and the United Kingdom. These phages exhibit a number of properties
      indicative of potential utility in phage therapy cocktails.

PMID- 23143290
TI  - Subjective and objective results of arthroscopic debridement of ulnar-sided TFCC
      (Palmer type 1B) lesions with stable distal radio-ulnar joint.
AB  - PURPOSE: The purpose of this study was to determine functional and subjective
      results of patients who received arthroscopic debridement for their TFCC Palmer
      1B lesions and to compare their results with those of arthroscopic suture repair.
      METHODS: Between March 2007 and August 2011, 36 patients were diagnosed with
      Palmer type 1B tears and underwent arthroscopic debridement. 31 patients (15
      males and 16 females) were followed up for an average of 26.7 months (+/-17.4
      months) postoperatively. Their average age was 36.7 years (+/-12.7 years). Follow
      up included the determination of range of motion (ROM), grip strength, pain, and
      wrist scores (modified Mayo wrist score (MMWS), Disabilities of the Arm, Shoulder
      and Hand questionnaire (DASH score)). RESULTS: Postoperative ROM averaged 99.2 %
      for the extension/flexion arc, 95.5 % for the radial/ulnar deviation arc, and
      99.4 % for the pronation/supination arc of motion when compared with the
      contralateral wrist. The MMWS was rated excellent in 48 % of patients, good in 39
      %, fair in 13 %, and poor in 0 %. The average DASH score was 17.02 (+/-14.92).
      There was a significant reduction in pain. The grip strength was 96.7 % (+/
      15.8), pulp-to-pulp pinch 101.9 % (+/-17.4), and the ulnar variance -0.12 +/-
      1.69 mm. CONCLUSIONS: Arthroscopic debridement of Palmer type 1B lesions in
      stable DRUJ yields satisfactory to excellent results. Our study showed similar
      results compared with the studies of arthroscopic suture repair with shorter
      postoperative care and fewer complications.

PMID- 23143291
TI  - Influence of anthropometric features on graft diameter in ACL reconstruction.
AB  - BACKGROUND: There is a paucity of literature regarding the influence of
      anthropometric features on the hamstring graft obtained in ACL reconstruction.
      This study was undertaken to assess the influence of anthropometric measurements
      on the graft diameter obtained at ACL reconstruction surgery within the European
      population. We hypothesise that anthropometric features do influence graft
      thickness in ACL reconstruction. MATERIALS AND METHODS: Data from 121 consecutive
      patients who had undergone ACL reconstruction by the same surgeon using quadruple
      hamstring grafts were analysed. The body mass index (BMI), height and weight of
      these patients were correlated with the graft diameter obtained during surgery.
      Regression analysis was undertaken to assess the influence of individual
      anthropometric variables on the graft diameter. RESULTS: There were 121 patients
      with mean age of 32 years (14-55). There was a statistically significant positive
      correlation individually between the height and graft diameter (r = 0.38, p <
      0.01) as well as between the body weight and graft diameter (r = 0.29, p < 0.01).
      However, when the body mass index was calculated, the correlation was not
      statistically significant (r = 0.08, p > 0.1). Regression analysis confirmed that
      BMI was not statistically significant as a predictor of hamstring graft diameter
      whereas height was statistically the most important predictor (F = 20.1; p <
      0.01).This yielded the predictive equation, graft diameter = 4.5 + 0.02 x Ht (in
      cm). CONCLUSION: Although body mass index did not significantly correlate, body
      height may be a predictive variable in predicting the graft diameter in ACL
      reconstruction and provide useful pre operative information.

PMID- 23143292
TI  - The urbilaterian brain revisited: novel insights into old questions from new
      flatworm clades.
AB  - Flatworms are classically considered to represent the simplest organizational
      form of all living bilaterians with a true central nervous system. Based on their
      simple body plans, all flatworms have been traditionally grouped together in a
      single phylum at the base of the bilaterians. Current molecular phylogenomic
      studies now split the flatworms into two widely separated clades, the acoelomorph
      flatworms and the platyhelminth flatworms, such that the last common ancestor of
      both clades corresponds to the urbilaterian ancestor of all bilaterian animals.
      Remarkably, recent comparative neuroanatomical analyses of acoelomorphs and
      platyhelminths show that both of these flatworm groups have complex anterior
      brains with surprisingly similar basic neuroarchitectures. Taken together, these
      findings imply that fundamental neuroanatomical features of the brain in the two
      separate flatworm groups are likely to be primitive and derived from the
      urbilaterian brain.

PMID- 23143293
TI  - Multicystic adenomatoid pancreatic hamartoma in a child: Case report and
      literature review.
AB  - INTRODUCTION: Pancreatic tumor is a rare condition in children, but reasonably
      common in adults. Histopathology in children also differs from that in adults,
      with most cases being pancreatoblastoma, solid pseudopapillary tumor, or
      pancreatic endocrine tumors. PRESENTATION OF CASE: A 14-month-old boy was noticed
      abdominal distension and referred to our hospital. Laboratory findings revealed
      leukocytosis and elevation of serum level of C-reactive protein and pancreatic
      enzymes. Radiological findings at admission were the huge abdominal cyst in
      abdominal computed tomography. As the levels of pancreatic enzyme elevated
      synchronous to oral feeding, total parenteral nutrition was needed. Besides
      radiographically the abdominal lesion changed from multiple large cystic type to
      multiple microcystic lesion including solid component over time. It was
      considered different diagnosis was pancreatic blastoma, pancreatic pseudo cyst,
      and lymphangioma and he was performed operation. The huge multicystic and
      partially solid tumor arising from the tail of pancreas existed from posterior of
      stomach to pelvic cavity. The tumor was completely resected without
      pancreatectomy and residual pancreas can be kept without tumor invasion.
      Histopathological finding was pancreatic hamartoma. DISCUSSION: Pancreatic
      hamartoma was extremely rare, and only 17 cases were previously reported in the
      literature. This is the first case that the change of radiographic findings
      overtime was shown. We reviewed 17 cases (4 cases in children) of pancreatic
      hamartoma including our case. CONCLUSION: Although extremely rare, pancreatic
      hamartoma should be considered in the differential diagnosis of cystic abdominal
      mass in children.

PMID- 23143294
TI  - Restricted access to the environment and quality of life in adult survivors of
      childhood brain tumors.
AB  - Survivors of pediatric brain tumors (BTs) are at-risk for late effects which may
      affect mobility within and access to the physical environment. This study
      examined the prevalence of and risk factors for restricted environmental access
      in survivors of childhood BTs and investigated the associations between reduced
      environmental access, health-related quality of life (HRQOL), and survivors'
      social functioning. In-home evaluations were completed for 78 BT survivors and 78
      population-based controls matched on age, sex, and zip-code. Chi-square tests and
      multivariable logistic regression models were used to calculate odds ratios (ORs)
      and 95 % confidence intervals (CIs) for poor environmental access and reduced
      HRQOL. The median age of survivors was 22 years at the time of study. Compared to
      controls, survivors were more likely to report avoiding most dimensions of their
      physical environment, including a single flight of stairs (p < 0.001), uneven
      surfaces (p < 0.001), traveling alone (p = 0.01), and traveling to unfamiliar
      places (p = 0.001). Overall, survivors were 4.8 times more likely to report poor
      environmental access (95 % CI 2.0-11.5, p < 0.001). In survivors, poor
      environmental access was associated with reduced physical function (OR = 3.6, 95
      % CI 1.0-12.8, p = 0.04), general health (OR = 6.0, 95 % CI 1.8-20.6, p = 0.002),
      and social functioning (OR = 4.3, 95 % CI 1.1-17.3, p = 0.03). Adult survivors of
      pediatric BTs were more likely to avoid their physical environment than matched
      controls. Restricted environmental access was associated with reduced HRQOL and
      diminished social functioning. Interventions directed at improving physical
      mobility may have significant impact on survivor quality of life.

PMID- 23143295
TI  - Use and implications of iron and other transition metals in environmental
      remediation processes.

PMID- 23143296
TI  - Toxicity of two types of silver nanoparticles to aquatic crustaceans Daphnia
      magna and Thamnocephalus platyurus.
AB  - Although silver nanoparticles (NPs) are increasingly used in various consumer
      products and produced in industrial scale, information on harmful effects of
      nanosilver to environmentally relevant organisms is still scarce. This paper
      studies the adverse effects of silver NPs to two aquatic crustaceans, Daphnia
      magna and Thamnocephalus platyurus. For that, silver NPs were synthesized where
      Ag is covalently attached to poly(vinylpyrrolidone) (PVP). In parallel, the
      toxicity of collargol (protein-coated nanosilver) and AgNO3 was analyzed. Both
      types of silver NPs were highly toxic to both crustaceans: the EC50 values in
      artificial freshwater were 15-17 ppb for D. magna and 20-27 ppb for T. platyurus.
      The natural water (five different waters with dissolved organic carbon from 5 to
      35 mg C/L were studied) mitigated the toxic effect of studied silver compounds up
      to 8-fold compared with artificial freshwater. The toxicity of silver NPs in all
      test media was up to 10-fold lower than that of soluble silver salt, AgNO3. The
      pattern of the toxic response of both crustacean species to the silver compounds
      was almost similar in artificial freshwater and in natural waters. The chronic 21
      day toxicity of silver NPs to D. magna in natural water was at the part-per
      billion level, and adult mortality was more sensitive toxicity test endpoint than
      the reproduction (the number of offspring per adult).

PMID- 23143297
TI  - Extent of intracellular storage in single and dual substrate systems under pulse
      feeding.
AB  - The study investigated the effect of acetate/starch mixture on the formation of
      storage biopolymers as compared with the storage mechanism in systems fed with
      these compounds as single substrates. Experiments involved two sequencing batch
      reactor sets operated at steady state, at sludge ages of 8 and 2 days,
      respectively. Each set included three different runs, one fed with acetate, the
      other with starch and the last one with the acetate/starch mixture. In single
      substrate systems with pulse feeding, starch was fully converted to glycogen,
      whereas 25 % of acetate was utilized for direct microbial growth at sludge age of
      8 days, together with polyhydroxybutyric acid (PHB) storage. The lower sludge age
      slightly increased this fraction to 30 %. Feeding of acetate/starch mixture
      induced a significant increase in acetate utilization for direct microbial
      growth; acetate fraction converted to PHB dropped down to 58 and 50 % at sludge
      ages of 8 and 2 days respectively, while starch remained fully converted to
      glycogen for both operating conditions. Parallel microbiological analyses based
      on FISH methodology confirmed that the biomass acclimated to the substrate
      mixture sustained microbial fractions capable of performing both glycogen and PHB
      storage.

PMID- 23143298
TI  - Inventories and concentration profiles of 137Cs in undisturbed soils in the
      northeast of Buenos Aires Province, Argentina.
AB  - Inventories and vertical distribution of (137)Cs were determined in La Plata
      region undisturbed soils, Argentina. A mean inventory value of 891 +/- 220
      Bq/m(2) was established, which is compatible with the values expected from
      atmospheric weapon tests fallout. The study was complemented with pH, organic
      carbon fraction, texture and mineralogical soil analyses. Putting together
      Southern Hemisphere (137)Cs inventory data, it is possible to correlate these
      data with the mean annual precipitations. The large differences in (137)Cs
      concentration profiles were attributed to soil properties, especially the clay
      content and the pH values. A convection-dispersion model with irreversible
      retention was used to fit the activity concentration profiles. The obtained
      effective diffusion coefficient and effective convection velocity parameters
      values were in the range from 0.2 cm(2)/y to 0.4 cm(2)/y and from 0.23 cm/y to
      0.43 cm/y, respectively. These data are in agreement with values reported in
      literature. In general, with the growth of clay content in the soil, there was an
      increase in the transfer rate from free to bound state. Finally, the highest
      transfer rate from free to bound state was obtained for soil pH value equal to 8.

PMID- 23143299
TI  - Components and strategies of nurse residency programs effective in new graduate
      socialization.
AB  - Patient needs and practice conditions demand that clinical nurses in acute care
      hospitals engage in a unique professional practice role-care and management of
      clinical situations for multiple patients, simultaneously. Nurse Residency
      Programs (NRPs) facilitate the integration of newly licensed registered nurses
      (NLRNs) into this professional practice role through competency development in
      seven management areas. Purpose of this study was to identify effective
      components and strategies of NRPs in each area. A sample of 907 nurses in 20
      Magnet hospitals with NRPs operative for at least 3 years participated in
      individual or small group interviews and 82 participant observations. All
      interviews were digitally recorded, transcribed, and analyzed thematically.
      Effective strategies were identified for all but one of the seven management
      areas. Suggestions for improvement in NRPs to better meet NLRN professional
      socialization needs, patient outcomes, and challenges of the health care system
      today are offered.

PMID- 23143300
TI  - The paradox of pharmacy: A profession's house divided.
AB  - OBJECTIVE: To describe the paradox in pharmacy between the vision of patient care
      and the reality of community pharmacy practice and to explore how integrated
      reimbursement for the retail prescription and linking cognitive patient care
      services directly to prescription processing could benefit the profession.
      SUMMARY: A dichotomy exists between what many pharmacists do and what they've
      been trained to do. Pharmacy leaders have formulated a vision for pharmacists to
      become more involved in direct patient care. All graduates now receive PharmD
      level training, and some leaders call for requirements of postgraduate residency
      training and board certification for pharmacists who provide patient care. How
      such requirements would relate to community pharmacy practice is unclear. The
      retail prescription remains the primary link between the pharmacist and the
      health care consumer. Cognitive services, such as medication therapy management
      (MTM), need to be integrated into the standard workflow of community pharmacies
      so as to become a natural extension of the professional services rendered in the
      process of filling a prescription. Current prescription fees are not sufficient
      to support legitimate professional services. A proposed integrated pricing system
      for retail prescriptions includes a $15 professional fee that is scaled upward
      for value-added services, such as MTM. CONCLUSION: Pharmacy includes a diversity
      of practice that has historically been a source of division. For pharmacists to
      reach their potential as patient care providers, the various factions within the
      profession must forge a unified vision of the future that addresses all realms of
      practice.

PMID- 23143301
TI  - Pathway-specific dopaminergic deficits in a mouse model of Angelman syndrome.
AB  - Angelman syndrome (AS) is a neurodevelopmental disorder caused by maternal
      deletions or mutations of the ubiquitin ligase E3A (UBE3A) allele and
      characterized by minimal verbal communication, seizures, and disorders of
      voluntary movement. Previous studies have suggested that abnormal dopamine
      neurotransmission may underlie some of these deficits, but no effective treatment
      currently exists for the core features of AS. A clinical trial of levodopa (L
      DOPA) in AS is ongoing, although the underlying rationale for this treatment
      strategy has not yet been thoroughly examined in preclinical models. We found
      that AS model mice lacking maternal Ube3a (Ube3a(m-/p+) mice) exhibit behavioral
      deficits that correlated with abnormal dopamine signaling. These deficits were
      not due to loss of dopaminergic neurons or impaired dopamine synthesis.
      Unexpectedly, Ube3a(m-/p+) mice exhibited increased dopamine release in the
      mesolimbic pathway while also exhibiting a decrease in dopamine release in the
      nigrostriatal pathway, as measured with fast-scan cyclic voltammetry. These
      findings demonstrate the complex effects of UBE3A loss on dopamine signaling in
      subcortical motor pathways that may inform ongoing clinical trials of L-DOPA
      therapy in patients with AS.

PMID- 23143302
TI  - Cancer susceptibility and embryonic lethality in Mob1a/1b double-mutant mice.
AB  - Mps one binder 1a (MOB1A) and MOB1B are key components of the Hippo signaling
      pathway and are mutated or inactivated in many human cancers. Here we show that
      intact Mob1a or Mob1b is essential for murine embryogenesis and that loss of the
      remaining WT Mob1 allele in Mob1a(Delta/Delta)1b(tr/+) or Mob1a(Delta/+)1b(tr/tr)
      mice results in tumor development. Because most of these cancers resembled
      trichilemmal carcinomas, we generated double-mutant mice bearing tamoxifen
      inducible, keratinocyte-specific homozygous-null mutations of Mob1a and Mob1b
      (kDKO mice). kDKO mice showed hyperplastic keratinocyte progenitors and defective
      keratinocyte terminal differentiation and soon died of malnutrition. kDKO
      keratinocytes exhibited hyperproliferation, apoptotic resistance, impaired
      contact inhibition, enhanced progenitor self renewal, and increased centrosomes.
      Examination of Hippo pathway signaling in kDKO keratinocytes revealed that loss
      of Mob1a/b altered the activities of the downstream Hippo mediators LATS and
      YAP1. Similarly, YAP1 was activated in some human trichilemmal carcinomas, and
      some of these also exhibited MOB1A/1B inactivation. Our results clearly
      demonstrate that MOB1A and MOB1B have overlapping functions in skin homeostasis,
      and exert their roles as tumor suppressors by regulating downstream elements of
      the Hippo pathway.

PMID- 23143303
TI  - CSF-1 signaling mediates recovery from acute kidney injury.
AB  - Renal tubule epithelia represent the primary site of damage in acute kidney
      injury (AKI), a process initiated and propagated by the infiltration of
      macrophages. Here we investigated the role of resident renal macrophages and
      dendritic cells in recovery from AKI after ischemia/reperfusion (I/R) injury or a
      novel diphtheria toxin-induced (DT-induced) model of selective proximal tubule
      injury in mice. DT-induced AKI was characterized by marked renal proximal tubular
      cell apoptosis. In both models, macrophage/dendritic cell depletion during the
      recovery phase increased functional and histologic injury and delayed
      regeneration. After I/R-induced AKI, there was an early increase in renal
      macrophages derived from circulating inflammatory (M1) monocytes, followed by
      accumulation of renal macrophages/dendritic cells with a wound-healing (M2)
      phenotype. In contrast, DT-induced AKI only generated an increase in M2 cells. In
      both models, increases in M2 cells resulted largely from in situ proliferation in
      the kidney. Genetic or pharmacologic inhibition of macrophage colony-stimulating
      factor (CSF-1) signaling blocked macrophage/dendritic cell proliferation,
      decreased M2 polarization, and inhibited recovery. These findings demonstrated
      that CSF-1-mediated expansion and polarization of resident renal
      macrophages/dendritic cells is an important mechanism mediating renal tubule
      epithelial regeneration after AKI.

PMID- 23143304
TI  - Mapping immune processes in intact tissues at cellular resolution.
AB  - Understanding the spatiotemporal changes of cellular and molecular events within
      an organism is crucial to elucidate the complex immune processes involved in
      infections, autoimmune disorders, transplantation, and neoplastic transformation
      and metastasis. Here we introduce a novel multicolor light sheet fluorescence
      microscopy (LSFM) approach for deciphering immune processes in large tissue
      specimens on a single-cell level in 3 dimensions. We combined and optimized
      antibody penetration, tissue clearing, and triple-color illumination to create a
      method for analyzing intact mouse and human tissues. This approach allowed us to
      successfully quantify changes in expression patterns of mucosal vascular
      addressin cell adhesion molecule-1 (MAdCAM-1) and T cell responses in Peyer's
      patches following stimulation of the immune system. In addition, we employed LSFM
      to map individual T cell subsets after hematopoietic cell transplantation and
      detected rare cellular events. Thus, we present a versatile imaging technology
      that should be highly beneficial in biomedical research.

PMID- 23143305
TI  - Intravaginal immunization with HPV vectors induces tissue-resident CD8+ T cell
      responses.
AB  - The induction of persistent intraepithelial CD8+ T cell responses may be key to
      the development of vaccines against mucosally transmitted pathogens, particularly
      for sexually transmitted diseases. Here we investigated CD8+ T cell responses in
      the female mouse cervicovaginal mucosa after intravaginal immunization with human
      papillomavirus vectors (HPV pseudoviruses) that transiently expressed a model
      antigen, respiratory syncytial virus (RSV) M/M2, in cervicovaginal keratinocytes.
      An HPV intravaginal prime/boost with different HPV serotypes induced 10-fold more
      cervicovaginal antigen-specific CD8+ T cells than priming alone. Antigen-specific
      T cell numbers decreased only 2-fold after 6 months. Most genital antigen
      specific CD8+ T cells were intra- or subepithelial, expressed alphaE-integrin
      CD103, produced IFN-gamma and TNF-alpha, and displayed in vivo cytotoxicity.
      Using a sphingosine-1-phosphate analog (FTY720), we found that the primed CD8+ T
      cells proliferated in the cervicovaginal mucosa upon HPV intravaginal boost.
      Intravaginal HPV prime/boost reduced cervicovaginal viral titers 1,000-fold after
      intravaginal challenge with vaccinia virus expressing the CD8 epitope M2. In
      contrast, intramuscular prime/boost with an adenovirus type 5 vector induced a
      higher level of systemic CD8+ T cells but failed to induce intraepithelial
      CD103+CD8+ T cells or protect against recombinant vaccinia vaginal challenge.
      Thus, HPV vectors are attractive gene-delivery platforms for inducing durable
      intraepithelial cervicovaginal CD8+ T cell responses by promoting local
      proliferation and retention of primed antigen-specific CD8+ T cells.

PMID- 23143306
TI  - ER stress-mediated autophagy promotes Myc-dependent transformation and tumor
      growth.
AB  - The proto-oncogene c-Myc paradoxically activates both proliferation and
      apoptosis. In the pathogenic state, c-Myc-induced apoptosis is bypassed via a
      critical, yet poorly understood escape mechanism that promotes cellular
      transformation and tumorigenesis. The accumulation of unfolded proteins in the ER
      initiates a cellular stress program termed the unfolded protein response (UPR) to
      support cell survival. Analysis of spontaneous mouse and human lymphomas
      demonstrated significantly higher levels of UPR activation compared with normal
      tissues. Using multiple genetic models, we demonstrated that c-Myc and N-Myc
      activated the PERK/eIF2alpha/ATF4 arm of the UPR, leading to increased cell
      survival via the induction of cytoprotective autophagy. Inhibition of PERK
      significantly reduced Myc-induced autophagy, colony formation, and tumor
      formation. Moreover, pharmacologic or genetic inhibition of autophagy resulted in
      increased Myc-dependent apoptosis. Mechanistically, we demonstrated an important
      link between Myc-dependent increases in protein synthesis and UPR activation.
      Specifically, by employing a mouse minute (L24+/-) mutant, which resulted in wild
      type levels of protein synthesis and attenuation of Myc-induced lymphomagenesis,
      we showed that Myc-induced UPR activation was reversed. Our findings establish a
      role for UPR as an enhancer of c-Myc-induced transformation and suggest that UPR
      inhibition may be particularly effective against malignancies characterized by c
      Myc overexpression.

PMID- 23143307
TI  - 8-Oxoguanine causes neurodegeneration during MUTYH-mediated DNA base excision
      repair.
AB  - 8-Oxoguanine (8-oxoG), a common DNA lesion caused by reactive oxygen species, is
      associated with carcinogenesis and neurodegeneration. Although the mechanism by
      which 8-oxoG causes carcinogenesis is well understood, the mechanism by which it
      causes neurodegeneration is unknown. Here, we report that neurodegeneration is
      triggered by MUTYH-mediated excision repair of 8-oxoG-paired adenine. Mutant mice
      lacking 8-oxo-2'-deoxyguanosine triphosphate-depleting (8-oxo-dGTP-depleting)
      MTH1 and/or 8-oxoG-excising OGG1 exhibited severe striatal neurodegeneration,
      whereas mutant mice lacking MUTYH or OGG1/MUTYH were resistant to
      neurodegeneration under conditions of oxidative stress. These results indicate
      that OGG1 and MTH1 are protective, while MUTYH promotes neurodegeneration. We
      observed that 8-oxoG accumulated in the mitochondrial DNA of neurons and caused
      calpain-dependent neuronal loss, while delayed nuclear accumulation of 8-oxoG in
      microglia resulted in PARP-dependent activation of apoptosis-inducing factor and
      exacerbated microgliosis. These results revealed that neurodegeneration is a
      complex process caused by 8-oxoG accumulation in the genomes of neurons and
      microglia. Different signaling pathways were triggered by the accumulation of
      single-strand breaks in each type of DNA generated during base excision repair
      initiated by MUTYH, suggesting that suppression of MUTYH may protect the brain
      under conditions of oxidative stress.

PMID- 23143308
TI  - Kras(G12D) and Nkx2-1 haploinsufficiency induce mucinous adenocarcinoma of the
      lung.
AB  - Mucinous adenocarcinoma of the lung is a subtype of highly invasive pulmonary
      tumors and is associated with decreased or absent expression of the transcription
      factor NK2 homeobox 1 (NKX2-1; also known as TTF-1). Here, we show that
      haploinsufficiency of Nkx2-1 in combination with oncogenic Kras(G12D), but not
      with oncogenic EGFR(L858R), caused pulmonary tumors in transgenic mice that were
      phenotypically similar to human mucinous adenocarcinomas. Gene expression
      patterns distinguished tumor goblet (mucous) cells from nontumorigenic airway and
      intestinal goblet cells. Expression of NKX2-1 inhibited urethane and oncogenic
      Kras(G12D)-induced tumorigenesis in vivo. Haploinsufficiency of Nkx2-1 enhanced
      Kras(G12D)-mediated tumor progression, but reduced EGFR(L858R)-mediated
      progression. Genome-wide analysis of gene expression demonstrated that a set of
      genes induced in mucinous tumors was shared with genes induced in a
      nontumorigenic chronic lung disease, while a distinct subset of genes was
      specific to mucinous tumors. ChIP with massively parallel DNA sequencing
      identified a direct association of NKX2-1 with the genes induced in mucinous
      tumors. NKX2-1 associated with the AP-1 binding element as well as the canonical
      NKX2-1 binding element. NKX2-1 inhibited both AP-1 activity and tumor colony
      formation in vitro. These data demonstrate that NKX2-1 functions in a context
      dependent manner in lung tumorigenesis and inhibits Kras(G12D)-driven mucinous
      pulmonary adenocarcinoma.

PMID- 23143310
TI  - Persistent truncus arteriosus with double aortic arch and mitral stenosis.
AB  - This report describes a case involving the rare combination of persistent truncus
      arteriosus type A2, double aortic arch, and mitral stenosis. At the age of 26
      days, the patient underwent division of the right-sided aortic arch with tracheal
      compression and bilateral pulmonary banding. Fontan completion was successfully
      achieved after separation of the pulmonary artery from the arterial trunk, atrial
      septostomy, and modified Blalock-Taussig shunt at the age of 7 months and
      bilateral bidirectional Glenn anastomosis at the age of 1 year and 3 months. At
      this writing, the patient is doing well 2 years and 6 months after Fontan
      completion.

PMID- 23143309
TI  - HERV-K-specific T cells eliminate diverse HIV-1/2 and SIV primary isolates.
AB  - The genetic diversity of HIV-1 represents a major challenge in vaccine
      development. In this study, we establish a rationale for eliminating HIV-1
      infected cells by targeting cellular immune responses against stable human
      endogenous retroviral (HERV) antigens. HERV DNA sequences in the human genome
      represent the remnants of ancient infectious retroviruses. We show that the
      infection of CD4+ T cells with HIV-1 resulted in transcription of the HML-2
      lineage of HERV type K [HERV-K(HML-2)] and the expression of Gag and Env
      proteins. HERV-K(HML-2)-specific CD8+ T cells obtained from HIV-1-infected human
      subjects responded to HIV-1-infected cells in a Vif-dependent manner in vitro.
      Consistent with the proposed mode of action, a HERV-K(HML-2)-specific CD8+ T cell
      clone exhibited comprehensive elimination of cells infected with a panel of
      globally diverse HIV-1, HIV-2, and SIV isolates in vitro. We identified a second
      T cell response that exhibited cross-reactivity between homologous HIV-1-Pol and
      HERV-K(HML-2)-Pol determinants, raising the possibility that homology between HIV
      1 and HERVs plays a role in shaping, and perhaps enhancing, the T cell response
      to HIV-1. This justifies the consideration of HERV-K(HML-2)-specific and cross
      reactive T cell responses in the natural control of HIV-1 infection and for
      exploring HERV-K(HML-2)-targeted HIV-1 vaccines and immunotherapeutics.

PMID- 23143311
TI  - Isolated cleft mitral valve with severe regurgitation resulting in a left
      inferior pulmonary vein varix diagnosed from cardiovascular magnetic resonance
      imaging.
AB  - Isolated cleft mitral valve (ICMV) is a rare entity not known to be related to
      pulmonary atresia with ventricular septal defect (PA-VSD). This report describes
      the use of cardiovascular magnetic resonance (CMR) imaging to diagnose ICMV in a
      patient with repaired PA-VSD who presented with incidental severe mitral
      regurgitation (MR) on follow-up echocardiography. An associated pulmonary varix
      secondary to the severe MR also was shown by CMR.

PMID- 23143312
TI  - Resource allocation strategies in Southeastern European health policy.
AB  - The past 23 years of post-socialist restructuring of health system funding and
      management patterns has brought many changes to small Balkan markets, putting
      them under increasing pressure to keep pace with advancing globalization.
      Socioeconomic inequalities in healthcare access are still growing across the
      region. This uneven development is marked by the substantial difficulties
      encountered by local governments in delivering medical services to broad sectors
      of the population. This paper presents the results of a systematic review of the
      following evidence: published reports on health system reforms in the region
      commissioned by WHO, IMF, World Bank, OECD, European Commission; all available
      published evidence on health economics, funding, reimbursement in world/local
      languages since 1989 indexed at Medline, Excerpta Medica and Google Scholar; in
      depth analysis of official website data on medical care financing related
      legislation among key public institutions such as national Ministries of health,
      Health Insurance Funds, Professional Associations were applicable, in local
      languages; correspondence with key opinion leaders in the field in their
      respective communities. Contributors were asked to answer a particular set of
      questions related to the issue, thus enlightening fresh legislative developments
      and hidden patterns of policy maker's behavior. Cost awareness is slowly
      expanding in regional management, academic and industrial establishment. The
      study provides an exact and comprehensive description of its current extent and
      legislative framework. Western Balkans policy makers would profit substantially
      from health-economics-based decision-making to cope with increasing difficulties
      in funding and delivering medical care in emerging markets with a rapidly growing
      demand for health services.

PMID- 23143313
TI  - Kinetin induces cell death in root cortex cells of Vicia faba ssp. minor
      seedlings.
AB  - The double fluorescence staining with acridine orange and ethidium bromide
      (AO/EB) revealed that treatment of Vicia faba ssp. minor seedlings with kinetin
      induced programmed cell death (PCD) in root cortex cells. Kinetin-induced cell
      death reflected by the morphological changes of nuclei including their
      invagination, volume increase, chromatin condensation and degradation as well as
      formation of micronuclei showed by AO/EB and 4,6-diamidino-2-phenylindol staining
      was accompanied by changes including increase in conductivity of cell
      electrolytes secreted to culture media, decrease in the number of the G1- and G2
      phase cells and appearance of fraction of hypoploid cells as the effect of DNA
      degradation without ladder formation. Decrease in the number of mitochondria and
      in the activity of cellular dehydrogenases, production of reactive oxygen species
      (ROS), appearance of small and then large lytic vacuoles and increase in the
      amount of cytosolic calcium ions were also observed. The PCD was also manifested
      by increased width and weight of apical fragments of roots as well as decreased
      length of cortex cells which led to shortening of the whole roots. The kinetin
      induced PCD process was almost completely inhibited by adenine, an inhibitor of
      phosphoribosyl transferase, and mannitol, an inhibitor of ROS production. These
      cell-death hallmarks and pathway of this process suggested that the induction of
      kinetin-specific vacuolar type of death, expressed itself with similar intensity
      on both morphological and metabolic levels, was a transient protecting whole
      roots and whole seedlings against elimination. 

PMID- 23143314
TI  - Valete, salvete.

PMID- 23143315
TI  - Dr Reginald Koettlitz (1860-1916): Arctic and Antarctic explorer.
AB  - Reginald Koettlitz was born in Ostend but moved to England as a child and
      qualified at Guy's Hospital. He was a general practitioner in County Durham for
      eight years before serving as doctor and geologist to the Jackson-Harmsworth
      Expedition to Franz-Josef Land in 1894-97. Thereafter he made further expeditions
      to Somaliland, Abyssinia and the Amazon before joining Captain Scott's Discovery
      Expedition to the Antarctic in 1901-04 as surgeon and botanist. After the
      expedition he emigrated to South Africa, where he worked as a general
      practitioner, dying in 1916.

PMID- 23143316
TI  - From precocious fame to mature obscurity: David Walker (1837-1917) MD, LRCSI,
      surgeon and naturalist to the Fox Arctic Expedition of 1857-59.
AB  - The Belfast-born David Walker was the 19-year-old surgeon and naturalist on the
      epic Fox Arctic Expedition (1857-59) that established the fate of Sir John
      Franklin's unsuccessful (1845) search for the North-West Passage. On return the
      crew were feted as heroes and decorated, and shared in a L5000 government bounty:
      Walker was also received by the Queen and (in Ireland) by the Lord Lieutenant,
      was honoured by the principal British and Irish natural history societies and his
      portrait was exhibited in the National Portrait Gallery, London. This paper
      describes his adventurous life, including the Fox Expedition, which from 1862 was
      spent abroad and included time in the Cariboo gold fields, service in the United
      States Army, practice in a notorious Californian frontier town and, in later
      life, the comparative quiet of general and occupational medical practice in
      Portland, Oregon. Once a household name, his death went unrecorded in the British
      and Irish medical and lay press.

PMID- 23143317
TI  - Medical biography and the surgeon.

PMID- 23143318
TI  - Hugh Neill (1806-64) and the early years of the Liverpool Ophthalmic Infirmary.
AB  - This account of the early history of ophthalmology in Liverpool refers
      particularly to Hugh Neill, one of the many Edinburgh-educated surgeons working
      in Liverpool during the early 19th century.

PMID- 23143319
TI  - The death of Robert Falcon Scott (1869-1912) and colleagues.
AB  - This year, 2012, marks the 100th anniversary of Captain Scott his reaching the
      South Pole and of his death on the return journey. There has been much discussion
      on the cause of death of Scott and his colleagues and, in particular, whether he
      died of scurvy. There has probably been even more discussion on the cause of
      death of Edgar Evans, one of Scott's companions. This paper reviews the topic.

PMID- 23143320
TI  - An Antarctic sealing expedition and the medical diary of William Spiers Bruce
      (1867-1921).
AB  - William Spiers Bruce was a medical student who sailed as ship's surgeon on the
      Balaena, one of the ships of the Dundee Whaling Expedition to the Antarctic (1892
      93). On this expedition he kept a diary listing his medical consultations and the
      treatments he administered. This paper considers the expedition and the diaries.

PMID- 23143321
TI  - Edward Adrian Wilson (1872-1912): polar explorer and artist.
AB  - Dr Edward Wilson was a polar explorer who accompanied Robert Falcon Scott (1868
      1912) on his expeditions to Antarctica in 1900 and 1910. He went with Scott to
      the South Pole and died with him on the return journey in 1912. Although
      medically qualified, he is now remembered more as a naturalist and as a talented
      artist recording the Antarctic expeditions.

PMID- 23143322
TI  - Medical memorials in Antarctica: a gazetteer of medical place-names.
AB  - In Antarctica an astonishing more than 300 'medical' place-names record the lives
      of surgeons and physicians who have served as leaders, clinicians and scientists
      in the field of polar medicine and other doctors memorialized for their service
      to medicine. These enduring medical memorials are to be found in the names of
      glaciers, mountains, capes and islands of the vast frozen Southern Continent.
      This Antarctic Medical Gazetteer features, inter alii, doctor-expedition leaders,
      including Jean-Baptiste Charcot (1867-1936) of France and Desmond Lugg (b. 1938)
      of Australia. The Medical Gazetteer lists 43 geographical features on Brabant
      Island that were named after famous doctors. This Gazetteer also includes a
      collection of medical place-names on the Loubet Coast honouring Dr John Cardell
      (1896-1966) and nine other pioneers who worked on the prevention of snow
      blindness and four islands of the Lyall Islands Group, including Surgeon Island,
      named after United States Antarctic Medical Officers. Eleven geographic features
      (mountains, islands, nunataks, lakes and more) are named after Australian doctors
      who have served with the Australian National Antarctic Research Expeditions based
      at Davis Station. Biographic memorials in Antarctica comprise a collective
      witness of esteem, honouring in particular those doctors who have served in
      Antarctica where death and injury remains a constant threat.

PMID- 23143323
TI  - Charles Dickens (1812-70): 'The longer I live the more I doubt the doctors'.

PMID- 23143324
TI  - The films of Sir Herbert Barker's (1869-1950) manipulative techniques.

PMID- 23143325
TI  - Purification and characterization of malate:quinone oxidoreductase from
      thermophilic Bacillus sp. PS3.
AB  - Several bacteria possess membrane-bound dehydrogenases other than cytosolic
      dehydrogenases in their respiratory chains. In many cases, the membrane-bound
      malate:quinone oxidoreductases (MQOs) are essential for growth. However, these
      MQOs are absent in mammalian mitochondria, and therefore may be a potential drug
      target for pathogenic bacteria. To characterize the kinetic properties of MQOs,
      we purified MQO from Bacillus sp. PS3, which is a gram-positive and thermophilic
      bacterium, and cloned the gene encoding MQO based on the obtained partial N
      terminus sequence. Purified MQOs showed a molecular mass of ~90 kDa, which was
      estimated using gel filtration, and it consists of two subunits with a molecular
      mass of ~50 kDa. Phylogenetic analysis showed a high similarity to the MQO of the
      Geobacillus group rather than the Bacillus group. Additionally, the purified
      enzyme was thermostable and it retained menaquinol reduction activity at high
      temperatures. Although it is difficult to conduct experiments using menaquinol
      because of its instability, we were able to measure the oxidase activity of
      cytochrome bd-type quinol oxidase by using menaquinol-1 by coupling this molecule
      with the menaquinol reduction reaction using purified MQOs.

PMID- 23143326
TI  - Preparation of materials in the presence of hydrogen peroxide: from discrete or
      "zero-dimensional" objects to bulk materials.
AB  - Based on selected examples from the literature, this perspective aims to provide
      a short overview of synthetic methods using hydrogen peroxide and/or peroxidic
      species for the elaboration of discrete or zero-dimensional species, as well as
      mono-, bi- and tri-dimensional materials. There are several advantages in using
      peroxidic species: no foreign ion or organic ligand is introduced in the reaction
      medium, they are relatively cheap compared to costly alkoxides, for example, and
      in certain favorable cases these methods allow the selective formation of a given
      oxide polymorph. The materials prepared are used in several important
      technological applications such as electrochromism, gas sensing and
      electrochemistry but, in this review, special emphasis is placed on oxidation
      catalysis. Indeed, the deposition of peroxo species on or into oxide supports
      generally leads to catalytic materials that display higher activities related to
      a better dispersion of the active metal species in the host matrix. This review
      also focuses on the use of hydrogen peroxide for the recycling of toxic metal
      containing spent materials such as those found in batteries for portable
      electronic devices.

PMID- 23143327
TI  - The impact of tumor heterogeneity on patient treatment decisions.

PMID- 23143328
TI  - Point: cancer stem cells--the evidence accumulates.

PMID- 23143329
TI  - Short- and long-term individual variation in cardiac troponin in patients with
      stable coronary artery disease.
AB  - BACKGROUND: A rise or fall of cardiac troponin is a prerequisite for the
      diagnosis of acute myocardial infarction. Defining significant changes requires
      knowledge of both biological and analytical variation. The short-term biological
      variation of cardiac troponin in healthy individuals is 3%-48%. However, healthy
      individuals may not be representative for patients in whom cardiac troponin
      measurement is often of clinical importance. Therefore, we studied the individual
      variation of cardiac troponin in patients with symptoms of stable coronary artery
      disease. METHODS: Twenty-four patients scheduled for elective coronary
      angiography were included. Blood samples were drawn once at enrollment and
      serially at six 4-h intervals on the day before coronary angiography. Cardiac
      troponin was measured with hs-cTn assays from Abbott Laboratories (premarket cTnI
      assay) and Roche Diagnostics (Elecsys((r)) cTnT assay with two different lots).
      RESULTS: The short-term individual variation in cardiac troponin I (cTnI) was
      14%, the reference change value (RCV) 49%, and RCV-log-normal (rise/fall) 54%/
      35%. The corresponding values for cTnT were 7%, 23%, and 26%/-21%. The long-term
      variation for cTnI was 24%, RCV 69%, and RCV-log-normal (rise/fall) 97%/-49%. The
      corresponding values for cTnT were 11%, 32%, and 37%/-27%. CONCLUSIONS: The short
      term individual variation of cardiac troponin in patients with symptoms of stable
      coronary artery disease is similar to the biological variation previously
      demonstrated in healthy individuals. Our results suggest that a change in cardiac
      troponin concentrations of >50% can be used in attempting to diagnose acute
      myocardial injury. To detect significant long-term changes in cardiac troponin
      concentrations, larger changes will be required.

PMID- 23143330
TI  - Nanoprobing of the effect of Cu(2+) cations on misfolding, interaction and
      aggregation of amyloid beta peptide.
AB  - Misfolding and aggregation of the amyloid beta-protein (Abeta) are hallmarks of
      Alzheimer's disease. Both processes are dependent on the environmental
      conditions, including the presence of divalent cations, such as Cu(2+). Cu(2+)
      cations regulate early stages of Abeta aggregation, but the molecular mechanism
      of Cu(2+) regulation is unknown. In this study we applied single molecule AFM
      force spectroscopy to elucidate the role of Cu(2+) cations on interpeptide
      interactions. By immobilizing one of two interacting Abeta42 molecules on a mica
      surface and tethering the counterpart molecule onto the tip, we were able to
      probe the interpeptide interactions in the presence and absence of Cu(2+) cations
      at pH 7.4, 6.8, 6.0, 5.0, and 4.0. The results show that the presence of Cu(2+)
      cations change the pattern of Abeta interactions for pH values between pH 7.4 and
      pH 5.0. Under these conditions, Cu(2+) cations induce Abeta42 peptide structural
      changes resulting in N-termini interactions within the dimers. Cu(2+) cations
      also stabilize the dimers. No effects of Cu(2+) cations on Abeta-Abeta
      interactions were observed at pH 4.0, suggesting that peptide protonation changes
      the peptide-cation interaction. The effect of Cu(2+) cations on later stages of
      Abeta aggregation was studied by AFM topographic images. The results demonstrate
      that substoichiometric Cu(2+) cations accelerate the formation of fibrils at pH
      7.4 and 5.0, whereas no effect of Cu(2+) cations was observed at pH 4.0. Taken
      together, the combined AFM force spectroscopy and imaging analyses demonstrate
      that Cu(2+) cations promote both the initial and the elongation stages of Abeta
      aggregation, but protein protonation diminishes the effect of Cu(2+).

PMID- 23143331
TI  - Use of high flow nasal cannula in critically ill infants, children, and adults: a
      critical review of the literature.
AB  - BACKGROUND: High flow nasal cannula (HFNC) systems utilize higher gas flow rates
      than standard nasal cannulae. The use of HFNC as a respiratory support modality
      is increasing in the infant, pediatric, and adult populations as an alternative
      to non-invasive positive pressure ventilation. OBJECTIVES: This critical review
      aims to: (1) appraise available evidence with regard to the utility of HFNC in
      neonatal, pediatric, and adult patients; (2) review the physiology of HFNC; (3)
      describe available HFNC systems (online supplement); and (4) review ongoing and
      planned trials studying the utility of HFNC in various clinical settings.
      RESULTS: Clinical neonatal studies are limited to premature infants. Only a few
      pediatric studies have examined the use of HFNC, with most focusing on this
      modality for viral bronchiolitis. In critically ill adults, most studies have
      focused on acute respiratory parameters and short-term physiologic outcomes with
      limited investigations focusing on clinical outcomes such as duration of therapy
      and need for escalation of ventilatory support. Current evidence demonstrates
      that HFNC generates positive airway pressure in most circumstances; however, the
      predominant mechanism of action in relieving respiratory distress is not well
      established. CONCLUSION: Current evidence suggests that HFNC is well tolerated
      and may be feasible in a subset of patients who require ventilatory support with
      non-invasive ventilation. However, HFNC has not been demonstrated to be
      equivalent or superior to non-invasive positive pressure ventilation, and further
      studies are needed to identify clinical indications for HFNC in patients with
      moderate to severe respiratory distress.

PMID- 23143332
TI  - Interleukin receptor activates a MYD88-ARNO-ARF6 cascade to disrupt vascular
      stability.
AB  - The innate immune response is essential for combating infectious disease.
      Macrophages and other cells respond to infection by releasing cytokines, such as
      interleukin-1beta (IL-1beta), which in turn activate a well-described, myeloid
      differentiation factor 88 (MYD88)-mediated, nuclear factor-kappaB (NF-kappaB)
      dependent transcriptional pathway that results in inflammatory-cell activation
      and recruitment. Endothelial cells, which usually serve as a barrier to the
      movement of inflammatory cells out of the blood and into tissue, are also
      critical mediators of the inflammatory response. Paradoxically, the cytokines
      vital to a successful immune defence also have disruptive effects on endothelial
      cell-cell interactions and can trigger degradation of barrier function and
      dissociation of tissue architecture. The mechanism of this barrier dissolution
      and its relationship to the canonical NF-kappaB pathway remain poorly defined.
      Here we show that the direct, immediate and disruptive effects of IL-1beta on
      endothelial stability in a human in vitro cell model are NF-kappaB independent
      and are instead the result of signalling through the small GTPase ADP
      ribosylation factor 6 (ARF6) and its activator ARF nucleotide binding site opener
      (ARNO; also known as CYTH2). Moreover, we show that ARNO binds directly to the
      adaptor protein MYD88, and thus propose MYD88-ARNO-ARF6 as a proximal IL-1beta
      signalling pathway distinct from that mediated by NF-kappaB. Finally, we show
      that SecinH3, an inhibitor of ARF guanine nucleotide-exchange factors such as
      ARNO, enhances vascular stability and significantly improves outcomes in animal
      models of inflammatory arthritis and acute inflammation.

PMID- 23143333
TI  - The calcium-sensing receptor regulates the NLRP3 inflammasome through Ca2+ and
      cAMP.
AB  - Mutations in the gene encoding NLRP3 cause a spectrum of autoinflammatory
      diseases known as cryopyrin-associated periodic syndromes (CAPS). NLRP3 is a key
      component of one of several distinct cytoplasmic multiprotein complexes
      (inflammasomes) that mediate the maturation of the proinflammatory cytokine
      interleukin-1beta (IL-1beta) by activating caspase-1. Although several models for
      inflammasome activation, such as K(+) efflux, generation of reactive oxygen
      species and lysosomal destabilization, have been proposed, the precise molecular
      mechanism of NLRP3 inflammasome activation, as well as the mechanism by which
      CAPS-associated mutations activate NLRP3, remain to be elucidated. Here we show
      that the murine calcium-sensing receptor (CASR) activates the NLRP3 inflammasome,
      mediated by increased intracellular Ca(2+) and decreased cellular cyclic AMP
      (cAMP). Ca(2+) or other CASR agonists activate the NLRP3 inflammasome in the
      absence of exogenous ATP, whereas knockdown of CASR reduces inflammasome
      activation in response to known NLRP3 activators. CASR activates the NLRP3
      inflammasome through phospholipase C, which catalyses inositol-1,4,5
      trisphosphate production and thereby induces release of Ca(2+) from endoplasmic
      reticulum stores. The increased cytoplasmic Ca(2+) promotes the assembly of
      inflammasome components, and intracellular Ca(2+) is required for spontaneous
      inflammasome activity in cells from patients with CAPS. CASR stimulation also
      results in reduced intracellular cAMP, which independently activates the NLRP3
      inflammasome. cAMP binds to NLRP3 directly to inhibit inflammasome assembly, and
      downregulation of cAMP relieves this inhibition. The binding affinity of cAMP for
      CAPS-associated mutant NLRP3 is substantially lower than for wild-type NLRP3, and
      the uncontrolled mature IL-1beta production from CAPS patients' peripheral blood
      mononuclear cells is attenuated by increasing cAMP. Taken together, these
      findings indicate that Ca(2+) and cAMP are two key molecular regulators of the
      NLRP3 inflammasome that have critical roles in the molecular pathogenesis of
      CAPS.

PMID- 23143334
TI  - Regulation of ISWI involves inhibitory modules antagonized by nucleosomal
      epitopes.
AB  - Chromatin-remodelling complexes (CRCs) mobilize nucleosomes to mediate the access
      of DNA-binding factors to their sites in vivo. These CRCs contain a catalytic
      subunit that bears an ATPase/DNA-translocase domain and flanking regions that
      bind nucleosomal epitopes. A central question is whether and how these flanking
      regions regulate ATP hydrolysis or the coupling of hydrolysis to DNA
      translocation, to affect nucleosome-sliding efficiency. ISWI-family CRCs contain
      the protein ISWI, which uses its ATPase/DNA-translocase domain to pump DNA around
      the histone octamer to enable sliding. ISWI is positively regulated by two
      'activating' nucleosomal epitopes: the 'basic patch' on the histone H4 tail, and
      extranucleosomal (linker) DNA. Previous work defined the HAND-SANT-SLIDE (HSS)
      domain at the ISWI carboxy terminus that binds linker DNA, needed for ISWI
      activity. Here we define two new, conserved and separate regulatory regions on
      Drosophila ISWI, termed AutoN and NegC, which negatively regulate ATP hydrolysis
      (AutoN) or the coupling of ATP hydrolysis to productive DNA translocation (NegC).
      The two aforementioned nucleosomal epitopes promote remodelling indirectly by
      preventing the negative regulation of AutoN and NegC. Notably, mutation or
      removal of AutoN and NegC enables marked nucleosome sliding without the H4 basic
      patch or extranucleosomal DNA, or the HSS domain, conferring on ISWI the
      biochemical attributes normally associated with SWI/SNF-family ATPases. Thus, the
      ISWI ATPase catalytic core is an intrinsically active DNA translocase that
      conducts nucleosome sliding, onto which selective 'inhibition-of-inhibition'
      modules are placed, to help ensure that remodelling occurs only in the presence
      of proper nucleosomal epitopes. This supports a general concept for the
      specialization of chromatin-remodelling ATPases, in which specific regulatory
      modules adapt an ancient active DNA translocase to conduct particular tasks only
      on the appropriate chromatin landscape.

PMID- 23143335
TI  - Nonlinear dendritic integration of sensory and motor input during an active
      sensing task.
AB  - Active dendrites provide neurons with powerful processing capabilities. However,
      little is known about the role of neuronal dendrites in behaviourally related
      circuit computations. Here we report that a novel global dendritic nonlinearity
      is involved in the integration of sensory and motor information within layer 5
      pyramidal neurons during an active sensing behaviour. Layer 5 pyramidal neurons
      possess elaborate dendritic arborizations that receive functionally distinct
      inputs, each targeted to spatially separate regions. At the cellular level,
      coincident input from these segregated pathways initiates regenerative dendritic
      electrical events that produce bursts of action potential output and circuits
      featuring this powerful dendritic nonlinearity can implement computations based
      on input correlation. To examine this in vivo we recorded dendritic activity in
      layer 5 pyramidal neurons in the barrel cortex using two-photon calcium imaging
      in mice performing an object-localization task. Large-amplitude, global calcium
      signals were observed throughout the apical tuft dendrites when active touch
      occurred at particular object locations or whisker angles. Such global calcium
      signals are produced by dendritic plateau potentials that require both vibrissal
      sensory input and primary motor cortex activity. These data provide direct
      evidence of nonlinear dendritic processing of correlated sensory and motor
      information in the mammalian neocortex during active sensation.

PMID- 23143336
TI  - Migraine and subsequent risk of breast cancer: a prospective cohort study.
AB  - PURPOSE: Previous studies have suggested that migraineurs are at decreased risk
      for developing breast cancer. Further prospective studies are warranted to
      confirm these results. In addition, studies evaluating migraine characteristics
      (e.g., migraine subtypes and frequency) are lacking. METHODS: We conducted a
      prospective cohort study among 39,696 participants in the Women's Health Study
      who were 45 years and older at study entry. Information on migraine was self
      reported with good validation rates. Incident breast cancer cases were confirmed
      by medical record review. We distinguished the following major endpoints: any
      breast cancer, a combined endpoint of invasive and in situ cases, in situ breast
      cancer only, and invasive breast cancer only. Cox proportional hazards models
      were used to calculate age- and multivariable-adjusted hazard ratios (HRs) and 95
      % confidence intervals (95 % CI). RESULTS: A total of 7,318 (18.4 %) women
      reported any migraine. During a mean follow-up time of 13.6 years, 432 in situ
      and 1,846 invasive breast cancer cases occurred. Migraine was not associated with
      breast cancer risk. The multivariable-adjusted HRs (95 % CI) were 1.10 (0.99
      1.22) for any breast cancer, 1.06 (0.83-1.35) for in situ breast cancer, and 1.11
      (0.99-1.25) for invasive breast cancer. The risk for developing breast cancer
      differed according to hormone receptor status with a suggestion of increased
      risks for hormone receptor negative tumors (HR ER-/PR- : 1.28, 95 % CI: 0.96
      1.71). We did not observe meaningful differences with regard to histologic
      subtype or according to migraine aura status or migraine attack frequency.
      CONCLUSIONS: Results of our study do not support the hypothesis that migraineurs
      have a decreased risk for breast cancer.

PMID- 23143337
TI  - On the probability of extinction in a periodic environment.
AB  - For a certain class of multi-type branching processes in a continuous-time
      periodic environment, we show that the extinction probability is equal to (resp.
      less than) 1 if the basic reproduction number R(0) is less than (resp. bigger
      than) 1. The proof uses results concerning the asymptotic behavior of cooperative
      systems of differential equations. In epidemiology the extinction probability may
      be used as a time-periodic measure of the epidemic risk. As an example we
      consider a linearized SEIR epidemic model and data from the recent measles
      epidemic in France. Discrete-time models with potential applications in
      conservation biology are also discussed.

PMID- 23143338
TI  - c.1643_1644delTG XPC mutation is more frequent in Moroccan patients with
      xeroderma pigmentosum.
AB  - Xeroderma pigmentosum is a rare autosomal recessive disease characterized by
      hypersensitivity to UV light which is due to alterations of the nucleotide
      excision repair pathway. Eight genes (XPA to XPG and XPV) are responsible for the
      disease. Among them, the XPC gene is known to be the most mutated in
      Mediterranean patients. The aim of this study was to determine the frequency of
      the most common XPC mutation and describe the clinical features of Moroccan
      patients with xeroderma pigmentosum. Twenty four patients belonging to 21
      unrelated Moroccan families and 58 healthy subjects were investigated. After
      clinical examination, the screening for the c.1643_1644delTG (p.Val548AlafsX25)
      mutation in the XPC gene was performed by PCR and automated sequencing of exon 9
      in all patients and controls. The molecular analysis showed that among the 24
      patients, 17 were homozygous for the c.1643_1644delTG mutation and all their
      tested parents were heterozygous, whereas the others (7 patients) did not carry
      the mutation. The frequency of this mutation was estimated to be 76.19 % (16/21
      families). None of the 58 healthy individuals carried this mutation. In addition,
      clinical investigation showed that the majority of the patients bearing this
      mutation have the same clinical features. Our results revealed that the
      p.Val548AlafsX25 mutation is the major cause (76.19 %) of xeroderma pigmentosum
      in Moroccan families. This would have an important impact on improving management
      of patients and their relatives.

PMID- 23143339
TI  - Cell-based approaches for the treatment of systemic inflammation.
AB  - Acute and chronic solid organ failures are costly disease processes with high
      mortality rates. Inflammation plays a central role in both acute and chronic
      organ failure, including heart, lung and kidney. In this regard, new therapies
      for these disorders have focused on inhibiting the mediators of inflammation,
      including cytokines and free radicals, with little or no success in clinical
      studies. Recent novel treatment strategies have been directed to cell-based
      rather than mediator-based approaches, designed to immunomodulate the deleterious
      effects of inflammation on organ function. One approach, cell therapy, replaces
      cells that were damaged in the acute or chronic disease process with
      stem/progenitor technology, to rebalance excessive inflammatory states. As an
      example of this approach, the use of an immunomodulatory role of renal epithelial
      progenitor cells to treat acute renal failure (ARF) and multiorgan failure
      arising from acute kidney injury is reviewed. A second therapeutic pathway, cell
      processing, does not incorporate stem/progenitor cells in the device, but rather
      biomimetic materials that remove and modulate the primary cellular components,
      which promote the worsening organ tissue injury associated with inflammation. The
      use of an immunomodulating leukocyte selective cytopheretic inhibitory device is
      also reviewed as an example of this cell processing approach. Both of these
      unconventional strategies have shown early clinical efficacy in pilot clinical
      trials and may transform the therapeutic approach to organ failure disorders.

PMID- 23143340
TI  - Translocation of dendrin to the podocyte nucleus in acute glomerular injury in
      patients with IgA nephropathy.
AB  - BACKGROUND: It has been reported that podocytopenia has been occurring with
      increasing disease severity in patients with IgA nephropathy (IgAN). Dendrin is
      localized at the slit diaphragm (SD) in podocytes. We showed that dendrin
      translocates to the nucleus of injured podocytes in experimental nephritis and
      the nuclear dendrin promotes podocyte apoptosis. It is still unknown whether
      dendrin translocates from the SD to podocyte nucleus in IgAN. We investigated the
      presence of nuclear dendrin in patients with IgAN and the association between the
      translocated dendrin to the podocyte nucleus and disease activity. METHODS:
      Fourteen adult patients with IgAN were enrolled. The pathological parameters were
      analyzed. Immunostaining of renal biopsy specimens and urinary sediments from
      IgAN or minimal change nephrotic syndrome (MCNS) as the control was performed.
      RESULTS: A positive correlation was observed between an acute extracapillary
      change and the number of dendrin-positive nuclei. The location of dendrin in the
      nuclei was found in urinary podocytes of IgAN. The number of dendrin-positive
      nuclei in urinary podocytes of IgAN was significantly higher than that of MCNS.
      Urinary podocytes, which expressed the apoptosis marker annexin V, were also
      detected in IgAN. The translocation of dendrin to the podocyte nucleus as well as
      strong cathepsin L staining were detected in the glomeruli of IgAN. CONCLUSION:
      An increasing number of dendrin-positive nuclei in the glomeruli suggest acute
      glomerular injury in IgAN. Apoptotic podocytes were detectable in the urine of
      IgAN. It appears that the translocation of dendrin to the podocyte nuclei
      enhances podocyte apoptosis in acute glomerular injury and leads to podocytopenia
      in patients with IgAN.

PMID- 23143341
TI  - Neuropsychological assessment of memory in preschoolers.
AB  - Memory is of fundamental importance for cognitive, social, and educational
      function, making it a target for neuropsychological assessment. The subject of
      this review is one particular type of memory, namely, episodic memory of unique
      events and experiences. Episodic memory allows for rapid, even one-trial learning
      of new information and retention of it for later retrieval. It depends on a
      particular neural substrate that undergoes a protracted developmental course. The
      review features discussion of some of the challenges associated with valid
      assessment of this specific form of memory in the preschool period, as well as a
      description and critical evaluation of available standardized measures. It also
      features description of two new approaches to assessment of episodic memory and
      their sensitivity to memory-specific deficits in the preschool years and in
      infancy. The review ends with introduction of the NIH Toolbox Picture Sequence
      Memory Test, designed as a measure of episodic memory in the preschool years and
      beyond.

PMID- 23143342
TI  - The rostral subcommissural ventral pallidum is a mix of ventral pallidal neurons
      and neurons from adjacent areas: an electrophysiological study.
AB  - The ventral pallidum (VP) is a part of the ventral striatopallidal system and is
      involved in reward-related behaviors. The VP is composed of a ventromedial (VPvm)
      and a dorsolateral (VPdl) subregion, and some rostral-caudal differences are
      reported. Study of the VP often focuses on the subcommissural VP, typically
      considered homogenous in spite of known subdivisions. In this work, we used slice
      electrophysiology combined with immunohistochemistry for marker neuropeptides to
      test whether the subcommissural VP is functionally homogenous. Using sagittal
      slices, we show that more lateral levels (2.40 mm) of the subcommissural VP are
      homogenous but that a more medial slice (1.90 mm) contains two types of neurons.
      One type, located more caudally, resembles neurons in the lateral subcommissural
      VP, with long aspiny dendrites, primarily GABAergic input, and characteristic
      electrophysiological properties, such as depolarized membrane potential and
      spontaneous action potential discharge. The second type of neuron, located mostly
      in the rostral subcommissural VP, shows properties that are akin to medium spiny
      neurons of adjacent regions, including spiny dendrites, major glutamatergic
      input, hyperpolarized membrane potential, and no spontaneous action potentials.
      The two types of neurons were present in both the VPvm and VPdl, implying that
      the mix is not a characteristic of histologically defined subregions. We conclude
      that at medial levels the rostral subcommissural VP contains a mix of typical
      ventral pallidal neurons and spiny neurons similar to those in adjacent regions.
      This observation needs to be considered when interpreting past experiments and
      designing future experiments in the subcommissural VP.

PMID- 23143343
TI  - Genomic transcriptional profiling in LOU/C/Jall rats identifies genes for
      successful aging.
AB  - Inbred LOU/C/Jall rats are currently described as a model of successful aging.
      These rats have a longer healthy median lifespan than many other strains, do not
      develop obesity, diabetes, or tumor and more importantly they do not show
      cognitive decline with aging. This is the first study to examine gene expression
      changes in the inbred LOU/C/Jall rat hippocampus and frontal cortex. Microarray
      data from animals aged 5 and 26 months were compared to that obtained from the
      classical Wistar rat strain to potentially identify only the genes associated
      with successful aging. We have thus identified a set of 15 genes in the
      hippocampus and 70 genes in the frontal cortex that could be grouped into several
      clearly delineated clusters of highly correlated genes associated with a
      diversity of biological processes, including regulation of plasticity,
      inflammatory response, metabolic, catabolic and homeostatic processes, and
      transcription. Such a multiplicity of gene networks and diversity of biological
      functions were not observed in the Wistar rat strain. The gene expression
      profiles identified in aged the LOU/C/Jall rats' hippocampus and frontal cortex
      should be related to their intact cognitive abilities, such as those assessed
      through spontaneous alternation.

PMID- 23143344
TI  - Differentiated parietal connectivity of frontal regions for "what" and "where"
      memory.
AB  - In a previous meta-analysis across almost 200 neuroimaging experiments, working
      memory for object location showed significantly stronger convergence on the
      posterior superior frontal gyrus, whereas working memory for identity showed
      stronger convergence on the posterior inferior frontal gyrus (dorsal to, but
      overlapping with Brodmann's area BA 44). As similar locations have been discussed
      as part of a dorsal frontal-superior parietal reach system and an inferior
      frontal grasp system, the aim of the present study was to test whether the
      regions of working-memory related "what" and "where" processing show a similar
      distinction in parietal connectivity. The regions that were found in the previous
      meta-analysis were used as seeds for functional connectivity analyses using task
      based meta-analytic connectivity modelling and task-independent resting state
      correlations. While the ventral seed showed significantly stronger connectivity
      with the bilateral intraparietal sulcus (IPS), the dorsal seed showed stronger
      connectivity with the bilateral posterior inferior parietal and the medial
      superior parietal lobule. The observed connections of regions involved in memory
      for object location and identity thus clearly demonstrate a distinction into
      separate pathways that resemble the parietal connectivity patterns of the dorsal
      and ventral premotor cortex in non-human primates and humans. It may hence be
      speculated that memory for a particular location and reaching towards it as well
      as object memory and finger positioning for manipulation may rely on shared
      neural systems. Moreover, the ensuing regions, in turn, featured differential
      connectivity with the bilateral ventral and dorsal extrastriate cortex,
      suggesting largely segregated bilateral connectivity pathways from the dorsal
      visual cortex via the superior and inferior parietal lobules to the dorsal
      posterior frontal cortex and from the ventral visual cortex via the IPS to the
      ventral posterior frontal cortex that may underlie action and cognition. 

PMID- 23143345
TI  - The use of non-standard motorcycle helmets in low- and middle-income countries: a
      multicentre study.
AB  - BACKGROUND: The use of non-standard motorcycle helmets has the potential to
      undermine multinational efforts aimed at reducing the burden of road traffic
      injuries associated with motorcycle crashes. However, little is known about the
      prevalence or factors associated with their use. METHODS: Collaborating
      institutions in nine low- and middle-income countries undertook cross-sectional
      surveys, markets surveys, and reviewed legislation and enforcement practices
      around non-standard helmets. FINDINGS: 5563 helmet-wearing motorcyclists were
      observed; 54% of the helmets did not appear to have a marker/sticker indicating
      that the helmet met required standards and interviewers judged that 49% of the
      helmets were likely to be non-standard helmets. 5088 (91%) of the motorcyclists
      agreed to be interviewed; those who had spent less than US$10 on their helmet
      were found to be at the greatest risk of wearing a non-standard helmet. Data were
      collected across 126 different retail outlets; across all countries, regardless
      of outlet type, standard helmets were generally 2-3 times more expensive than non
      standard helmets. While seven of the nine countries had legislation prohibiting
      the use of non-standard helmets, only four had legislation prohibiting their
      manufacture or sale and only three had legislation prohibiting their import.
      Enforcement of any legislation appeared to be minimal. INTERPRETATION: Our
      findings suggest that the widespread use of non-standard helmets in low- and
      middle-income countries may limit the potential gains of helmet use programmes.
      Strategies aimed at reducing the costs of standard helmets, combined with both
      legislation and enforcement, will be required to maximise the effects of existing
      campaigns.

PMID- 23143346
TI  - Acute occupational injury among adolescent farmworkers from South Texas.
AB  - PURPOSE: This combined cross-sectional/cohort study addressed research gaps by
      estimating the rate of non-fatal occupational injury and identifying potential
      determinants among a population of adolescent farmworkers who are largely
      Hispanic and migrant. METHODS: The cohort included 410 farmworkers (aged 13-19
      years) attending high school in South Texas along the border with Mexico. Data
      collection involved a self-administered, Web-based survey that solicited
      information on demographics, farm work variables including person-time at risk,
      occupational injury, health status and health risk behaviours. Cox regression was
      used to identify potential risk factors for non-fatal injury events experienced
      during a 9-month recall period. RESULTS: Depending on the definition of injury,
      the rate of non-fatal injury ranged from 27.0-73.6/100 full time equivalents.
      Variables with an increased and statistically significant HR in an adjusted Cox
      model included: age groups <15 years-old (5.82) and 16 years-old (4.47), usually
      sleeping <8 h during the week (2.10), feeling tense, stressed or anxious
      sometimes/often (2.25), not watching TV (2.65), working around ditches (2.01) and
      detasseling (2.70). CONCLUSIONS: The high observed rates of non-fatal injury
      combined with the potential negative consequences and cost of these injuries
      signifies a compelling need for injury prevention efforts targeting adolescent,
      Hispanic, farmworkers.

PMID- 23143347
TI  - Stimulant treatment and injury among children with attention deficit
      hyperactivity disorder: an application of the self-controlled case series study
      design.
AB  - OBJECTIVE: The aim of the present work was to assess the short-term effects of
      stimulant medication use on risk of injury among children diagnosed as having
      attention deficit hyperactivity disorder (ADHD). METHODS: The study group for
      this self-controlled case series study was children aged 1-18 years old diagnosed
      as having ADHD who experienced an incident medically-attended injury event and
      received at least one prescription for stimulant medication between 1993 and 2008
      (n=328), identified from The Health Improvement Network primary care database
      from the UK. Conditional Poisson regression was used to estimate incident rate
      ratios (IRR) and 95% CIs for injury comparing periods of time exposed to
      stimulant medication to unexposed periods. RESULTS: Among children with ADHD
      prescribed stimulant medication, the rate of medically-attended injury was
      decreased during periods of stimulant medication use as compared to unexposed
      periods (IRR 0.68, 95% CI 0.50 to 0.91). There was evidence of a protective
      association among males and among children aged 10-14 years. This effect did not
      change over time on treatment. CONCLUSIONS: Stimulant medication use may decrease
      the risk of injury among children treated for ADHD, although unmeasured time
      varying confounding may be an alternative explanation. Injury risk may be
      considered during the decision-making process with regard to medication
      continuation among children with ADHD.

PMID- 23143348
TI  - A unique aortic arterial meshwork with a major aortopulmonary collateral artery,
      a major arteriovenous collateral artery, and a coronary arteriovenous fistula in
      a young man with a bicuspid aortic valve.
AB  - This report describes a case of an asymptomatic 18-year-old boy with a grade 1/6
      ejection systolic murmur in the aortic area referred for an echocardiographic
      study to rule out a congenital heart disease. The patient had situs solitus,
      levocardia, bicuspid aortic valve, dilation of the proximal portions of the right
      coronary artery, and arteriovenous coronary fistula of the anomalous coronary
      branch originating from the anterior descending coronary artery into the main
      pulmonary artery. In addition he had a unique aortic arterial meshwork
      constituted by arteries originating from the inferior and posterior aspect of the
      distal portion of the transverse aortic arch, intersegmentary arteries
      originating from the lateral and anterior aspect of the proximal portion of the
      descending aorta, and the true bronchial artery with a major arteriovenous
      collateral artery draining into the superior vena cava and the superior division
      of the left lower pulmonary vein as well as a major aortopulmonary collateral
      artery anastomosed with a bronchial artery and draining into the posterior aspect
      of the right pulmonary artery. The use of transthoracic two-dimensional color
      flow Doppler echocardiography, magnetic resonance angiography and multislice
      computed tomography to establish a detailed morphologic analysis and the presence
      of associated anomalies in patients with a bicuspid aortic valve are discussed. 

PMID- 23143349
TI  - Increased incidence of coronary artery origin anomalies associated with isolated
      patent ductus arteriosus.
AB  - Coronary artery anomalies may increase the risk of sudden death. Despite
      awareness of this association with certain congenital heart anomalies such as
      tetralogy of Fallot and transposition of the great arteries, it is thought to be
      an infrequent finding in cases of isolated patent ductus arteriosus (PDA). The
      authors report their experience with coronary anomalies in PDA patients. This
      study aimed to estimate the incidence of coronary artery anomalies in patients
      with PDA. The study reviewed 206 angiograms of PDA patients obtained between 1999
      and 2011 to determine the origin of the coronary arteries. In 102 angiograms
      (49.5 %), the origin of the coronary arteries could be adequately visualized. An
      anomalous origin of coronary arteries was detected in 11 of the 102 patients
      (10.8 %). Seven of these patients had a single common coronary artery origin (6.8
      %). One patient had an aberrant origin of the left coronary artery from the
      noncoronary sinus, and three patients had an aberrant origin of the right
      coronary artery: two from the left coronary sinus and one from the noncoronary
      sinus. These findings suggest that the incidence of coronary artery anomalies in
      association with an isolated PDA may be considerably higher than expected and
      previously reported. In view of the increased risk for sudden death with coronary
      anomalies, a reasonable approach is to determine the coronary artery origin and
      pathway after the diagnosis of an isolated PDA.

PMID- 23143350
TI  - A triple challenge: thrombocytopenia in a 7-year-old girl with unrepaired d
      transposition of the great arteries, ventricular septal defect, and pulmonary
      hypertension.
AB  - Thrombocytopenia can be a real challenge during cardiac surgery in children with
      cyanotic congenital heart disease. This report describes a 7-year-old girl with d
      transposition of the great arteries, ventricular septal defect, pulmonary
      hypertension, chronic thrombocytopenia, polycythemia, and chronic renal
      impairment. The thrombocytopenia improved several days after splenectomy. The
      child then underwent a successful arterial switch operation with ventricular
      septal defect closure. 

PMID- 23143351
TI  - Subclinical hypothyroidism in grown-up congenital heart disease patients.
AB  - Subclinical hypothyroidism usually is asymptomatic, but it can be associated with
      various adverse cardiologic outcomes. With the objective of gaining insight into
      the role of thyroid-stimulating hormone (TSH) in congenital heart abnormalities,
      this study measured serum TSH concentrations in different subtypes of grown-up
      congenital heart disease (GUCHD) patients. Serum TSH (reference range, 0.34-5.6
      mIU/L), creatinine, cholesterol, C-reactive protein (CRP), N-terminal proB-type
      natriuretic peptide (NT-pro-BNP), and 24-h proteinuria were measured in 249 GUCHD
      patients. Of 24 GUCHD patients (9.6 %) with a TSH level higher than 5.6 mUI/L,
      nine were cyanotic (37.5 %) and seven (29.1 %) had Down syndrome. The GUCHD
      patients with serum TSH exceeding 5.6 mIU/L had a significantly higher level of
      serum NT-pro-BNP (195.1 [0.28; 5,280.3] vs 57.6 [0.00; 929.8]; p = 0.001) and CRP
      (0.30 [0.06; 1.87] vs 0.16 [0.00; 1.40]; p = 0.011] than those with a TSH level
      of 5.6 mIU/L or lower. No significant differences were found in serum creatinine,
      lipids, or 24-h proteinuria between the two groups. The T4 concentrations in the
      GUCHD patients with TSH exceeding 5.6 mIU/L were within the normal range (0.89 +/
      0.23 ng/dL). In the multivariate analysis, cyanosis (odds ratio [OR], 6,399; 95
      % confidence interval [CI] 2,296-17,830; p < 0.001), Down syndrome (OR, 6,208; 95
      % CI, 1,963-19,636; p = 0.002), and NT-pro-BNP concentrations (OR, 1,001; 95 %
      CI, 1,000-1,002; p < 0.026) proved to be risk factors for TSH levels higher than
      5.6 mIU/L. Because subclinical hypothyroidism entails a cardiovascular risk, the
      authors postulate that TSH screening should be included in the routine follow-up
      evaluation of GUCHD patients with cyanosis or Down syndrome.

PMID- 23143352
TI  - Inhaled iloprost as a rescue therapy for transposition of the great arteries with
      persistent pulmonary hypertension of the newborn.
AB  - Transposition of the great arteries (TGA) in the newborn combined with persistent
      pulmonary hypertension was reported previously to occur in 3-12 % of full-term
      neonates with TGA. Right-to-left shunting at the ductal level causes severe
      hypoxemia despite prostaglandin infusion and balloon atrial septostomy. Although
      the introduction of inhaled nitric oxide (iNO) has improved the prognosis, this
      condition still is associated with high preoperative mortality. This report
      describes the case of a newborn with TGA and persistent pulmonary hypertension,
      which was managed successfully with oral sildenafil, iNO, and inhaled iloprost
      during life-threatening acute pulmonary hypertension, thus preventing the use of
      extracorporeal membrane oxygenation.

PMID- 23143353
TI  - A computational framework for investigating the positional stability of aortic
      endografts.
AB  - Endovascular aneurysm repair (Greenhalgh in N Engl J Med 362(20):1863-1871, 2010)
      techniques have revolutionized the treatment of thoracic and abdominal aortic
      aneurysm disease, greatly reducing the perioperative mortality and morbidity
      associated with open surgical repair techniques. However, EVAR is not free of
      important complications such as late device migration, endoleak formation and
      fracture of device components that may result in adverse events such as aneurysm
      enlargement, need for long-term imaging surveillance and secondary interventions
      or even death. These complications result from the device inability to withstand
      the hemodynamics of blood flow and to keep its originally intended post-operative
      position over time. Understanding the in vivo biomechanical working environment
      experienced by endografts is a critical factor in improving their long-term
      performance. To date, no study has investigated the mechanics of contact between
      device and aorta in a three-dimensional setting. In this work, we developed a
      comprehensive Computational Solid Mechanics and Computational Fluid Dynamics
      framework to investigate the mechanics of endograft positional stability. The
      main building blocks of this framework are: (1) Three-dimensional non-planar
      aortic and stent-graft geometrical models, (2) Realistic multi-material
      constitutive laws for aorta, stent, and graft, (3) Physiological values for blood
      flow and pressure, and (4) Frictional model to describe the contact between the
      endograft and the aorta. We introduce a new metric for numerical quantification
      of the positional stability of the endograft. Lastly, in the results section, we
      test the framework by investigating the impact of several factors that are
      clinically known to affect endograft stability. 

PMID- 23143354
TI  - Effective antimicrobial stewardship in a long-term care facility through an
      infectious disease consultation service: keeping a LID on antibiotic use.
AB  - DESIGN: We introduced a long-term care facility (LTCF) infectious disease (ID)
      consultation service (LID service) that provides on-site consultations to
      residents of a Veterans Affairs (VA) LTCF. We determined the impact of the LID
      service on antimicrobial use and Clostridium difficile infections at the LTCF.
      SETTING: A 160-bed VA LTCF. METHODS: Systemic antimicrobial use and positive C.
      difficile tests at the LTCF were compared for the 36 months before and the 18
      months after the initiation of the ID consultation service through segmented
      regression analysis of an interrupted time series. RESULTS: Relative to that in
      the preintervention period, total systemic antibiotic administration decreased by
      30% (P<.001), with significant reductions in both oral (32%; P<.001) and
      intravenous (25%; P=.008) agents. The greatest reductions were seen for
      tetracyclines (64%; P<.001), clindamycin (61%; P<.001),
      sulfamethoxazole/trimethoprim (38%; P<.001), fluoroquinolones (38%; P<.001), and
      beta-lactam/beta-lactamase inhibitor combinations (28%; P<.001). The rate of
      positive C. difficile tests at the LTCF declined in the postintervention period
      relative to preintervention rates (P=.04). CONCLUSIONS: Implementation of an LTCF
      ID service led to a significant reduction in total antimicrobial use. Bringing
      providers with ID expertise to the LTCF represents a new and effective means to
      achieve antimicrobial stewardship.

PMID- 23143355
TI  - Transfer from high-acuity long-term care facilities is associated with carriage
      of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae: a
      multihospital study.
AB  - OBJECTIVE: To determine whether transfer from a long-term care facility (LTCF) is
      a risk factor for colonization with Klebsiella pneumoniae carbapenemase (KPC)
      producing Enterobacteriaceae upon acute care hospital admission. DESIGN:
      Microbiologic survey and nested case-control study. SETTING: Four hospitals in a
      metropolitan area (Chicago) with an early KPC epidemic. PATIENTS: Hospitalized
      adults. METHODS: Patients transferred from LTCFs were matched 1?1 to patients
      admitted from the community by age (+/- 10 years), admitting clinical service,
      and admission date (+/- 2 weeks). Rectal swab specimens were collected within 3
      days after admission and tested for KPC-producing Enterobacteriaceae. Demographic
      and clinical information was extracted from medical records. RESULTS: One hundred
      eighty patients from LTCFs were matched to 180 community patients. KPC-producing
      Enterobacteriaceae colonization was detected in 15 (8.3%) of the LTCF patients
      and 0 (0%) of the community patients ([Formula: see text]). Prevalence of
      carriage differed by LTCF subtype: 2 of 135 (1.5%) patients from skilled nursing
      facilities without ventilator care (SNFs) were colonized upon admission, compared
      to 9 of 33 (27.3%) patients from skilled nursing facilities with ventilator care
      (VSNFs) and 4 of 12 (33.3%) patients from long-term acute care hospitals (LTACHs;
      [Formula: see text]). In a multivariable logistic regression model adjusted for a
      propensity score that predicted LTCF subtype, patients admitted from VSNFs or
      LTACHs had 7.0-fold greater odds of colonization (ie, odds ratio; 95% confidence
      interval, 1.3-42; [Formula: see text]) with KPC-producing Enterobacteriaceae than
      patients from an SNF. CONCLUSIONS: Patients admitted to acute care hospitals from
      high-acuity LTCFs (ie, VSNFs and LTACHs) were more likely to be colonized with
      KPC-producing Enterobacteriaceae than were patients admitted from the community.
      Identification of healthcare facilities with a high prevalence of colonized
      patients presents an opportunity for focused interventions that may aid regional
      control efforts.

PMID- 23143356
TI  - Device-associated infections among neonatal intensive care unit patients:
      incidence and associated pathogens reported to the National Healthcare Safety
      Network, 2006-2008.
AB  - OBJECTIVE: To describe rates and pathogen distribution of device-associated
      infections (DAIs) in neonatal intensive care unit (NICU) patients and compare
      differences in infection rates by hospital type (children's vs general
      hospitals). PATIENTS AND SETTING: Neonates in NICUs participating in the National
      Healthcare Safety Network from 2006 through 2008. METHODS: We analyzed central
      line-associated bloodstream infections (CLABSIs), umbilical catheter-associated
      bloodstream infections (UCABs), and ventilator-associated pneumonia (VAP) among
      304 NICUs. Differences in pooled mean incidence rates were examined using Poisson
      regression; nonparametric tests for comparing medians and rate distributions were
      used. RESULTS: Pooled mean incidence rates by birth weight category (750 g or
      less, 751-1,000 g, 1,001-1,500 g, 1,501-2,500 g, and more than 2,500 g,
      respectively) were 3.94, 3.09, 2.25, 1.90, and 1.60 for CLABSI; 4.52, 2.77, 1.70,
      0.91, and 0.92 for UCAB; and 2.36, 2.08, 1.28, 0.86, and 0.72 for VAP. When rates
      of infection between hospital types were compared, only pooled mean VAP rates
      were significantly lower in children's hospitals than in general hospitals among
      neonates weighing 1,000 g or less; no significant differences in medians or rate
      distributions were noted. Pathogen frequencies were coagulase-negative
      staphylococci (28%), Staphylococcus aureus (19%), and Candida species (13%) for
      bloodstream infections and Pseudomonas species (16%), S. aureus (15%), and
      Klebsiella species (14%) for VAP. Of 673 S. aureus isolates with susceptibility
      results, 33% were methicillin resistant. CONCLUSIONS: Neonates weighing 750 g or
      less had the highest DAI incidence. With the exception of VAP, pooled mean NICU
      incidence rates did not differ between children's and general hospitals.
      Pathogens associated with these infections can pose treatment challenges;
      continued efforts at prevention need to be applied to all NICU settings.

PMID- 23143357
TI  - Incidence, secular trends, and outcomes of prosthetic joint infection: a
      population-based study, olmsted county, Minnesota, 1969-2007.
AB  - CONTEXT: The epidemiology of prosthetic joint infection (PJI) in a population
      based cohort has not been studied in the United States. OBJECTIVES: To provide an
      accurate assessment of the true incidence, secular trends, clinical
      manifestations, microbiology, and treatment outcomes of PJI in a population-based
      cohort. DESIGN: Historical cohort study. SETTING: Olmsted County, Minnesota.
      PARTICIPANTS: Residents who underwent total knee arthroplasty (TKA) or total hip
      arthroplasty (THA) between January 1, 1969, and December 31, 2007. METHODS:
      Incidence rates and trends in PJI were assessed using the Kaplan-Meier method and
      log-rank test, as were treatment outcomes among PJI case patients. RESULTS: A
      total of 7,375 THAs or TKAs were implanted in residents of Olmsted County during
      the study period. Seventy-five discrete joints in 70 individuals developed PJI,
      during a mean +/- SD follow-up of [Formula: see text] years. The cumulative
      incidence of PJI was 0.5%, 0.8%, and 1.4% after 1, 5, and 10 years after
      arthroplasty, respectively. Overall, the rate of survival free of clinical
      failure after treatment of PJI was 76.8% (95% confidence interval [CI], 64.3
      85.2) and 65.2% (95% CI, 33.1-76.2) at 3 and 5 years, respectively. The incidence
      and treatment outcomes did not significantly differ by decade of implantation,
      patient age at implantation, gender, or joint location. CONCLUSIONS: The
      incidence of PJI is relatively low in a population-based cohort and is a function
      of age of the prosthesis. Incidence trends and outcomes have not significantly
      changed over the past 40 years.

PMID- 23143358
TI  - On the role of length of stay in healthcare-associated bloodstream infection.
AB  - DESIGN: We conducted a retrospective cohort study to examine the role played by
      length of hospital stay in the risk of healthcare-associated bloodstream
      infection (BSI), independent of demographic and clinical risk factors for BSI.
      PATIENTS: We employed data from 113,893 admissions from inpatients discharged
      between 2006 and 2008. SETTING: Large tertiary healthcare center in New York
      City. METHODS: We estimated the crude and adjusted hazard of BSI by conducting
      logistic regression using a person-day data structure. The covariates included in
      the fully adjusted model included age, sex, Charlson score of comorbidity, renal
      failure, and malignancy as static variables and central venous catheterization,
      mechanical ventilation, and intensive care unit stay as time-varying variables.
      RESULTS: In the crude model, we observed a nonlinear increasing hazard of BSI
      with increasing hospital stay. This trend was reduced to a constant hazard when
      fully adjusted for demographic and clinical risk factors for BSI. CONCLUSION: The
      association between longer length of hospital stay and increased risk of
      infection can largely be explained by the increased duration of stay among those
      who have underlying morbidity and require invasive procedures. We should take
      caution in attributing the association between length of stay and BSI to a direct
      negative impact of the healthcare environment.

PMID- 23143359
TI  - Identifying the risk factors for hospital-acquired methicillin-resistant
      Staphylococcus aureus (MRSA) infection among patients colonized with MRSA on
      admission.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a major
      pathogen in hospital-acquired infections. MRSA-colonized inpatients who may
      benefit from undergoing decolonization have not been identified. OBJECTIVE: To
      identify risk factors for MRSA infection among patients who are colonized with
      MRSA at hospital admission. DESIGN: A case-control study. SETTING: A 146-bed
      Veterans Affairs hospital. PARTICIPANTS: Case patients were those patients
      admitted from January 2003 to August 2011 who were found to be colonized with
      MRSA on admission and then developed MRSA infection. Control subjects were those
      patients admitted during the same period who were found to be colonized with MRSA
      on admission but who did not develop MRSA infection. METHODS: A retrospective
      review. RESULTS: A total of 75 case patients and 150 control subjects were
      identified. A stay in the intensive care unit (ICU) was the significant risk
      factor in univariate analysis (P<.001). Prior history of MRSA (P=.03), transfer
      from a nursing home (P=.002), experiencing respiratory failure (P<.001), and
      receipt of transfusion (P=.001) remained significant variables in multivariate
      analysis. Prior history of MRSA colonization or infection (P=.02]), difficulty
      swallowing (P=.04), presence of an open wound (P=.02), and placement of a central
      line (P=.02) were identified as risk factors for developing MRSA infection for
      patients in the ICU. Duration of hospitalization, readmission rate, and mortality
      rate were significantly higher in case patients than in control subjects (P <
      .001, .001, and <.001, respectively). CONCLUSIONS: MRSA-colonized patients
      admitted to the ICU or admitted from nursing homes have a high risk of developing
      MRSA infection. These patients may benefit from undergoing decolonization.

PMID- 23143360
TI  - Cost-effectiveness of different screening strategies (single or dual) for the
      diagnosis of tuberculosis infection in healthcare workers.
AB  - OBJECTIVE: To evaluate the cost-effectiveness of a dual strategy of tuberculin
      skin test (TST) and QuantiFERON-TB Gold (QFT-G) for screening of latent
      tuberculosis infection (LTBI) in healthcare workers (HCWs) and, as a secondary
      objective, to study relationships between TST results, QFT-G results, and
      sociodemographic factors. DESIGN: Cross-sectional prospective study. SETTING:
      University hospital in Madrid. PARTICIPANTS: A total of 103 HCWs. METHODS: QFT-G
      was requested for all positive TST results; QFT-G results were compared with TST
      results, and their relationships with sociodemographic factors were analyzed. A
      cost-effectiveness analysis was conducted for the dual strategy (TST/QFT-G) and
      for TST or QFT alone, taking into account the indication of and compliance with
      isoniazid, the risk of hepatotoxicity, and postexposure tuberculosis. RESULTS: Of
      all HCWs studied, 42.3% showed a positive result by QFT-G, and 49.5% had received
      bacille Calmette-Guerin (BCG) vaccination; no significant association was
      detected between BCG and QFT-G results. Increased TST was linked to higher
      positive QFT-G values (TST of 5-9.9 mm, 27.6%; TST of 15 mm or more, 56.5%;
      P=.03). The probability of positive QFT-G results was 1.04 times higher for each
      year of age (odds ratio, 1.04 [95% confidence interval, 1.01-1.09]; P=.0257). The
      incremental cost per active TB case prevented was lower for TST/QFT-G than for
      the other strategies studied (?14,211 per 1,000 HCWs). The number of people
      treated for LTBI per case of active TB prevented (number needed to treat) for
      TST/QFT-G was lower than for TST alone (17.2 vs 95.3 and 88.7 with the 5- and 10
      mm cutoff value, respectively) or QFT-G alone (69.6). CONCLUSIONS: Dual strategy
      with TST/QFT-G is more cost-effective than TST or QFT-G alone for the diagnosis
      of LTBI in HCWs.

PMID- 23143361
TI  - Infections associated with use of ultrasound transmission gel: proposed
      guidelines to minimize risk.

PMID- 23143362
TI  - Gordonia bronchialis sternal wound infection in 3 patients following open heart
      surgery: intraoperative transmission from a healthcare worker.
AB  - We describe an investigation of 3 postoperative Gordonia bronchialis sternal
      infections. A nurse anesthetist was identified as the source of the outbreak, her
      scrubs likely becoming contaminated by her home washing machine. The outbreak
      ended after disposal of the implicated washing machine. Domestic laundering of
      surgical scrubs may need reevaluation.

PMID- 23143363
TI  - Risk factors for gastrointestinal tract colonization with extended-spectrum beta
      lactamase (ESBL)-producing Escherichia coli and Klebsiella species in
      hospitalized patients.
AB  - We describe the prevalence of and risk factors for colonization with extended
      spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella species
      (ESBL-EK) in hospitalized patients. The prevalence of colonization with ESBL-EK
      was 2.6%. Colonization was associated with cirrhosis, longer duration of hospital
      stay prior to surveillance, and prior exposure to clindamycin or meropenem.

PMID- 23143364
TI  - Impact of vancomycin minimum inhibitory concentration on mortality among
      critically ill patients with methicillin-resistant Staphylococcus aureus
      bacteremia.
AB  - We retrospectively evaluated 99 intensive care unit patients with methicillin
      resistant Staphylococcus aureus bacteremia to determine whether having a
      vancomycin minimum inhibitory concentration (MIC) of 2 mg/L affected mortality.
      This MIC was found in 5.1% of patients and was associated with the probability of
      death (adjusted odds ratio, 13.9 [95% confidence interval, 1.1-171.2])
      independent of other factors.

PMID- 23143365
TI  - Epidemiology of vancomycin-resistant enterococci with reduced susceptibility to
      daptomycin.
AB  - A retrospective case-case control study was conducted, including 60 cases with
      daptomycin-nonsusceptible vancomycin-resistant enterococci (DNS-VRE) matched to
      cases with daptomycin-susceptible VRE and to uninfected controls (1?1?3 ratio).
      Immunosuppression, presence of comorbid conditions, and prior exposure to
      antimicrobials were independent predictors of DNS-VRE, although prior daptomycin
      exposure occurred rarely. In summary, a case-case control study identified
      independent risk factors for the isolation of DNS-VRE: immunosuppression,
      multiple comorbid conditions, and prior exposures to cephalosporines and
      metronidazole.

PMID- 23143366
TI  - Efficacy of different cleaning and disinfection methods against Clostridium
      difficile spores: importance of physical removal versus sporicidal inactivation.
AB  - We tested the effectiveness of disinfectants and wipe methods against Clostridium
      difficile spores. Wiping with nonsporicidal agents (physical removal) was
      effective in removing more than 2.9 log(10) C. difficile spores. Wiping with
      sporicidal agents eliminated more than 3.90 log(10) C. difficile spores (physical
      removal and/or inactivation). Spraying with a sporicide eliminated more than 3.44
      log(10) C. difficile spores but would not remove debris.

PMID- 23143367
TI  - The precision of human-generated hand-hygiene observations: a comparison of human
      observation with an automated monitoring system.
AB  - We compared the observations of nearly 1,400 hand-hygiene-related events recorded
      by an automated system and by human observers. Observation details differed for
      38% of these events. Two likely explanations for these inconsistencies were the
      distance between the observer and the event and the busyness of the clinic.

PMID- 23143368
TI  - Current approach to latent tuberculosis diagnosis and treatment among medical
      center occupational health physicians.
AB  - We surveyed physicians in a national occupational medicine society regarding
      diagnosis of latent tuberculosis infection in healthcare workers. Most
      respondents used a combination of skin testing and interferon gamma release
      assays. Respondents integrating interferon gamma release assays into screening
      placed greater importance on employee acceptability and convenience.

PMID- 23143369
TI  - Black-water floods and hospital-based postflood mold investigations.

PMID- 23143370
TI  - Intensity of vascular catheter use in critical care: impact on catheter
      associated bloodstream infection rates and association with severity of illness.

PMID- 23143371
TI  - Natural language processing to identify foley catheter-days.

PMID- 23143372
TI  - National survey of infection preventionists: policies for discontinuation of
      contact precautions for methicillin-resistant Staphylococcus aureus and
      vancomycin-resistant enterococcus.

PMID- 23143373
TI  - Descriptive analysis of healthcare-associated infections other than bloodstream,
      respiratory, urinary tract, or surgical site infections, 2001-2011.

PMID- 23143374
TI  - The influence of environmental temperature and air humidity on the maintenance of
      sterility of surgical instruments sterilized in different wraps.

PMID- 23143375
TI  - Safety culture and hand hygiene: linking attitudes to behavior.

PMID- 23143376
TI  - Do patients feel comfortable asking healthcare workers to wash their hands?

PMID- 23143377
TI  - Air quality of a hospital after closure for black-water flood: an occupational
      health concern?

PMID- 23143378
TI  - Variability of adenosine triphosphate-based bioluminescence assay readings among
      drug-resistant pathogens.

PMID- 23143379
TI  - Increasing influenza vaccination rates among hospital employees without a
      mandatory policy.

PMID- 23143382
TI  - Positive self-perceptions as a mediator of religious involvement and health
      behaviors in a national sample of African Americans.
AB  - Self-esteem and self-efficacy are theorized to serve as mediators of the
      relationship between religious involvement and health outcomes. Studies
      confirming these relationships have produced mixed evidence. This study examined
      whether self-esteem and self-efficacy mediate the relationship between religious
      involvement (beliefs, behaviors) and a set of modifiable health behaviors in a
      national probability sample of African Americans. African Americans, in general,
      are relatively high in religious involvement and have higher than average rates
      of chronic disease. Participants were interviewed by telephone, and a Religion
      Health Mediational Model was tested using structural equation modeling. Results
      suggest that self-esteem and self-efficacy at least in part mediate the
      relationship between religious beliefs (e.g., relationship with God) and greater
      fruit and vegetable consumption, and lower alcohol consumption. Religious
      behaviors (e.g., service attendance) were found to have direct, unmediated
      effects on health behaviors. Findings have implications for church-based health
      promotion in African American communities such as education or support groups. 

PMID- 23143383
TI  - Scaling down the size of BaLnF5 nanocrystals (Ln = La, Gd, and Lu) with the Ln3+
      size.
AB  - Monodispersed Yb(3+)(20%)/Er(3+)(2%)-doped BaLnF(5) (Ln = La, Gd, Lu)
      nanocrystals were synthesized by a thermal decomposition method. The study
      reveals that the size of the nanocrystals scales down with the Ln(3+) size
      without affecting the phase and shape of the nanocrystals. This is supported by
      the microscopic and optical properties.

PMID- 23143384
TI  - Delayed postpartum hemorrhage: the implications of making a diagnostic mistake.

PMID- 23143385
TI  - The feasibility of halfcycle reconstruction in high heart rates in coronary CT
      angiography using 320-row CT.
AB  - Our aim was to investigate when halfcycle reconstruction (HCR) was feasible in
      patients who were predicted to have a heart rate over 65 bpm in coronary CT
      angiography (CTA) using 320-row CT. Seventy-four patients who underwent multiple
      heart beat scanning were included. The time to reach 230 HU at the ascending
      aorta during the bolus tracking scan was recorded (T230). HCR image and
      multicycle reconstruction (MCR) image were reconstructed for each patient. Image
      quality for each coronary segment was rated on a 3-point scale (3: good, 1:
      poor). For each patient, we determined that a single beat acquisition was
      feasible for diagnosis (HCR group) when the number of segments graded score 1 in
      the HCR image was the same or less than that in the MCR image. Otherwise, we
      included the patients in the MCR group. HCR group and MCR group included 38 and
      36 patients, respectively. Regression analysis showed that body height >1.66 m
      (odds ratio (OR), 5.74; CI 1.59-25.6; p < 0.007), T230 >16 s (OR 3.11; CI 1.07
      9.58; p = 0.04), and heart rate <=72 bpm (OR 3.18; CI 1.11-9.49; p = 0.03) were
      related with the HCR group. When all three criteria were fulfilled, the
      calculated probability that MCR would improve image quality was only 7 %. When
      the heart rate is <=72 bpm, single heart beat acquisition is feasible for
      patients with body height >1.66 m and T230 > 16 s in coronary CTA using 320-row
      CT.

PMID- 23143386
TI  - Human cartilage fragments in a composite scaffold for single-stage cartilage
      repair: an in vitro study of the chondrocyte migration and the influence of TGF
      beta1 and G-CSF.
AB  - PURPOSE: Minced chondral fragments are becoming popular as a source of cells for
      cartilage repair, as a growing interest is developing towards one-stage
      procedures to treat cartilage lesions. The purpose of this study is to (A)
      compare cell outgrowth from cartilage fragments of adult and young donors using
      two different types of scaffolds and (B) evaluate the influence of transforming
      growth-factor-beta1 (TGF-beta1) and granulocyte colony-stimulating factor (G-CSF)
      on chondrocyte behaviour. METHODS: In part (A) cartilage fragments from adult and
      young donors were either loaded onto an HA-derivative injectable paste scaffold
      or onto an HA-derivative membrane scaffold. Construct sections were then examined
      for cell counting after 1, 2 and 3 months. In part (B) only membrane scaffolds
      were prepared using cartilage fragments from young donors. Constructs were
      cultured either in standard growth medium or in the presence of specific growth
      factors, such as TGF-beta1 or G-CSF or TGF-beta1 + G-CSF. After 1 month,
      construct sections were examined for cell counting. Expression of chondrocyte
      markers (SOX9, CD151, CD49c) and proliferative markers (beta-catenin, PCNA) was
      assessed using immunofluorescence techniques, both in unstimulated construct
      sections and in cells from unstimulated and stimulated construct cultures.
      RESULTS: Part (A): histological analysis showed age-dependent and time-dependent
      chondrocyte migration. A significant difference (p < 0.05) was observed between
      young and older donors at the same time point. No difference was detected between
      the two types of scaffolds within the same group at the same time point. Part
      (B): after 1 month, the number of migrating cells/area significantly increased
      due to exposure to TGF-beta1 and/or G-CSF (p < 0.05). Immunofluorescence revealed
      that outgrowing cells from unstimulated scaffold sections were positive for SOX9,
      CD151, CD49c and G-CSF receptor. Immunofluorescence of cells from construct
      cultures showed an increase in beta-catenin in all stimulated groups and an
      increased PCNA expression in G-CSF-exposed cultures (p < 0.05). CONCLUSION:
      Outgrowing cells may represent a subset of chondrocytes undergoing a phenotypic
      shift towards a proliferative state. TGF-beta1, and to a greater extent G-CSF,
      may accelerate this outgrowth. The clinical relevance of this study may involve a
      potential future clinical application of scaffolds preloaded with growth factors
      as an additional coating for chondral fragments. Indeed, a controlled delivery of
      G-CSF, widely employed in various clinical settings, might improve the repair
      process driven by minced human cartilage fragments during one-stage cartilage
      repair.

PMID- 23143387
TI  - Reliability, validity and responsiveness of the Spanish version of the Knee
      Injury and Osteoarthritis Outcome Score (KOOS) in patients with chondral lesion
      of the knee.
AB  - PURPOSE: The purpose of this study was to perform a cross-cultural adaptation of
      the Knee Injury and Osteoarthritis Outcome Score (KOOS) into Spanish and to
      evaluate the psychometric properties of this version in patients with chondral
      lesion of the knee, as expressed by its validity, reliability and responsiveness.
      METHODS: The translation followed an established forward-backward translation
      procedure with independent translations and counter-translation, according to the
      recommendations for the cross-cultural adaptation of HRQL measures. Twenty
      Spanish-speaking patients who underwent arthroscopic surgery for knee cartilage
      defects with a microfracture technique were enrolled in the study. Diagnosis was
      made based on clinical criteria and radiological confirmation through magnetic
      resonance imaging. Patients showing signs of instability, axial malalignment or
      generalised knee osteoarthritis were excluded from the study. RESULTS: Cronbach's
      alpha value for the study of the questionnaire was >0.7 in all the KOOS domains
      except for Symptoms domain. The test-retest reliability was confirmed with an ICC
      value greater than 0.8 in all the KOOS domains. A significant agreement between
      the KOOS domains and the scales of the SF-36 with related content, particularly
      in the areas of physical function and pain, was observed. CONCLUSION: Spanish
      KOOS questionnaire is valid, reliable and responsive for use in Spanish patients
      with symptomatic chondral lesion of the knee receiving surgical intervention.

PMID- 23143388
TI  - Consideration of religious sentiments while selecting a biological product for
      knee arthroscopy.
AB  - PURPOSE: There is an increasing use of various synthetic and biological products
      in orthopaedics. The use of a biological product can be a major area of concern
      for patients of various cultures/religions. The purpose of this work is to study
      various restrictions in different faiths and their compatibility with available
      products focused on cartilage repair. METHODS: A systematic search in several
      databases, CINAHL, EMBASE, Global health, PubMed, MEDLINE and the Cochrane
      collaboration, was performed to find out various religious beliefs of some major
      religions regarding the use of animal products. Hindu, Muslim, Christian, Jewish
      and Buddhist faiths were studied to find out whether animal-derived surgical
      implants are permitted. Major religious scholars were asked about their opinions,
      and guidelines related to human/religious ethics were evaluated. A market survey
      was carried out to find out biological contents of various products and their
      compatibility. RESULTS: Jews and Muslims have religious restrictions for porcine
      products, while Hindus reject bovine products. Vegetarian Hindus reject usage of
      any animal product. Most Christians do not have any restrictions except those who
      follow vegetarian dietary regulations. Though there is no prohibition for the use
      of animal products in Buddhism, a code of non-violence to animals is being
      followed. However, difference of opinion exists about interpretation of these
      dietary guidelines for surgical usage amongst various scholars. CONCLUSION:
      Products of biological origin have a definite restriction for various religions,
      with few exceptions. Surgeons should know the source of the product and should be
      aware of the basic requirements of the patient's faith. Patient should be
      informed about the source of the product and alternative if available, and an
      informed consent may be considered. LEVEL OF EVIDENCE: Type of study, Level V.

PMID- 23143389
TI  - Effect of head posture on the healthy human carotid bifurcation hemodynamics.
AB  - Head and neck postures may cause morphology changes to the geometry of the
      carotid bifurcation (CB) that alter the low and oscillating wall shear stress
      (WSS) regions previously reported as important in the development of
      atherosclerosis. Here the right and left CB were imaged by MRI in two healthy
      subjects in the neutral head posture with the subject in the supine position and
      in two other head postures with the subject in the prone position: (1) rightward
      rotation up to 80 degrees , and (2) leftward rotation up to 80 degrees . Image
      based computational models were constructed to investigate the effect of posture
      on arterial geometry and local hemodynamics. The area exposure to unfavorable
      hemodynamics, based on thresholds set for oscillatory shear index (OSI), WSS and
      relative residence time, was used to quantify the hemodynamic impact on the wall.
      Torsion of the head was found to: (1) cause notable changes in the bifurcation
      and internal carotid artery angles and, in most cases, on cross-sectional area
      ratios for common, internal and external carotid artery, (2) change the spatial
      distribution of wall regions exposed to unfavorable hemodynamics, and (3) cause a
      marked change in the hemodynamic burden on the wall when the OSI was considered.
      These findings suggest that head posture may be associated with the genesis and
      development of atherosclerotic disease as well as complications in stenotic and
      stented vessels.

PMID- 23143390
TI  - Granular cell tumor of the cervical esophagus: case report and literature review
      of an unusual cause of Dysphagia.
AB  - Granular cell tumors (GCT) of the head and neck are not uncommon; however,
      involvement of the cervical esophagus is rare. Characterized by an infiltrative
      growth pattern, these benign tumors are historically difficult to surgically
      excise and are radioresistant. We present here a case of dysphagia caused by a
      GCT of the cervical esophagus. Work up with ultrasound-guided fine needle
      aspiration was suggestive of a GCT due to the presence of cohesive cells with
      granular cytoplasm that were S-100 and CD68 positive with immunostaining, and PAS
      positive with histochemistry. Resection required removal of a portion of the
      muscular wall of the esophagus sparing the overlying mucosa. The patient is
      currently asymptomatic and without recurrence after 10 month follow-up. Review of
      the literature revealed 19 reports of cervical esophageal GCTs. There is a female
      preponderance (75%), with an average age of 41 years. Dysphagia and weight loss
      are the most common presenting symptoms. The average tumor size on presentation
      was 2.7 cm, with symptomatic tumors being significantly larger than asymptomatic
      lesions; the latter was present in 25% of patients. Concurrent GCTs in the upper
      aerodigestive tract were identified in 35% of cases. Approximately 30% of tumors
      required segmental cervical esophageal resection. The purpose of this report is
      to describe the epidemiology and treatment of GCTs of the cervical esophagus.
      Lesions should be addressed early with complete surgical excision to prevent
      growth necessitating more morbid surgery. Due to the high rate of concurrent
      GCTs, upper endoscopy is advised in the workup of these patients.

PMID- 23143391
TI  - Daphnias: from the individual based model to the large population equation.
AB  - The class of deterministic 'Daphnia' models treated by Diekmann et al. (J Math
      Biol 61:277-318, 2010) has a long history going back to Nisbet and Gurney (Theor
      Pop Biol 23:114-135, 1983) and Diekmann et al. (Nieuw Archief voor Wiskunde 4:82
      109, 1984). In this note, we formulate the individual based models (IBM)
      supposedly underlying those deterministic models. The models treat the
      interaction between a general size-structured consumer population ('Daphnia') and
      an unstructured resource ('algae'). The discrete, size and age-structured Daphnia
      population changes through births and deaths of its individuals and through their
      aging and growth. The birth and death rates depend on the sizes of the
      individuals and on the concentration of the algae. The latter is supposed to be a
      continuous variable with a deterministic dynamics that depends on the Daphnia
      population. In this model setting we prove that when the Daphnia population is
      large, the stochastic differential equation describing the IBM can be
      approximated by the delay equation featured in (Diekmann et al., loc. cit.).

PMID- 23143392
TI  - 4G/5G plasminogen activator inhibitor-1 and -308 A/G tumor necrosis factor-alpha
      promoter gene polymorphisms in Argentinean lupus patients: focus on lupus
      nephritis.
AB  - We investigated the relationship between the 4G/5G plasminogen activator
      inhibitor (PAI-1) and -308 A/G tumor necrosis factor-alpha (TNF-alpha)
      polymorphisms and the clinical and biochemical features of systemic lupus
      erythematosus (SLE) in an Argentinean patient cohort. A total of 402 patients
      were studied, including 179 SLE patients and 223 healthy individuals. PCR-RLFP
      was used to determine the genotypes of the 4G/5G PAI-1 and -308 A/G TNF-alpha
      polymorphisms. SLE patients with lupus nephritis (LN) (n = 86) were compared with
      patients without LN (n = 93). Additionally, LN patients were divided into
      proliferative LN and non-proliferative LN groups according to the results of the
      renal biopsies. No significant differences were noted in the genotype
      distributions or allele frequencies of these TNF-alpha and PAI-1 polymorphisms
      between SLE patients and controls. There were higher numbers of criteria for SLE,
      more lupus flares and higher damage scores in LN patients, but there were similar
      frequencies of anti-phospholipid antibody (APA) positivity and anti-phospholipid
      syndrome. No significant difference was noted for any studied variable between
      the proliferative LN and non-proliferative LN groups except for the presence of
      APA. We found no significant differences in the TNF-alpha and PAI-1 genotype
      distributions or allele frequencies between groups. We found that the -308 A/G
      TNF-alpha and 4G/5G PAI-1 polymorphisms are not associated with susceptibility to
      SLE in an Argentinean population. We also did not find any association between
      the presence of any specific allele or genotype and the development of LN in SLE
      patients. Finally, no association was noted between either of the two
      polymorphisms and the severity of renal disease.

PMID- 23143393
TI  - Interactions between the neuromodulatory systems and the amygdala: exploratory
      survey using the Allen Mouse Brain Atlas.
AB  - Neuromodulatory systems originate in nuclei localized in the subcortical region
      of the brain and control fundamental behaviors by interacting with many areas of
      the central nervous system. An exploratory survey of the cholinergic,
      dopaminergic, noradrenergic, and serotonergic receptor expression energy in the
      amygdala, and in the neuromodulatory areas themselves was undertaken using the
      Allen Mouse Brain Atlas. The amygdala was chosen because of its importance in
      cognitive behavior and its bidirectional interaction with the neuromodulatory
      systems. The gene expression data of 38 neuromodulatory receptor subtypes were
      examined across 13 brain regions. The substantia innominata of the basal
      forebrain and regions of the amygdala had the highest amount of receptor
      expression energy for all four neuromodulatory systems examined. The ventral
      tegmental area also displayed high receptor expression of all four
      neuromodulators. In contrast, the locus coeruleus displayed low receptor
      expression energy overall. In general, cholinergic receptor expression was an
      order of magnitude greater than other neuromodulatory receptors. Since the nuclei
      of these neuromodulatory systems are thought to be the source of specific
      neurotransmitters, the projections from these nuclei to target regions may be
      inferred by receptor expression energy. The comprehensive analysis revealed many
      connectivity relations and receptor localization that had not been previously
      reported. The methodology presented here may be applied to other neural systems
      with similar characteristics, and to other animal models as these brain atlases
      become available. 

PMID- 23143394
TI  - Liquid formulations for stabilizing IgMs during physical stress and long-term
      storage.
AB  - PURPOSE: To develop a liquid formulation for IgMs to survive physical stress and
      storage. METHODS: Stabilizing formulations for 8 monoclonal immunoglobulin (IgMs)
      were found using differential scanning calorimetry (DSC). In these formulations,
      the IgMs were subjected to stress and storage and analyzed by size exclusion
      chromatography and fluorescence activated cell sorting. Structure was analyzed
      using small-angle X-ray scattering (SAXS). RESULTS: The highest conformational
      stability was found near the isoelectric point and further enhanced by addition
      of sorbitol, sucrose and glycine. For 2 IgMs, the pH optimum for conformational
      and storage stability did not correspond. Lowering the pH led to the desired
      storage stability. Optimized formulations prevented aggregation and fragmentation
      from shear stress, freeze-thaw cycles, accelerated storage and real time storage
      at 4 degrees C and -20 degrees C for 12 months. Optimized formulations also
      preserved immunoreactivity for 12 months. SAXS indicated that IgM in stabilizing
      conditions was closer to the structural IgM model (2RCJ) and less susceptible for
      aggregation. CONCLUSIONS: A long-term stabilizing formulation for 8 IgMs was
      found comprising 20% sorbitol and 1 M glycine at pH 5.0-5.5 which may have broad
      utility for other IgMs. Formulation development using DSC and accelerated storage
      was evaluated in this study and may be used for other proteins.

PMID- 23143395
TI  - YAP mediates crosstalk between the Hippo and PI(3)K-TOR pathways by suppressing
      PTEN via miR-29.
AB  - Organ development is a complex process governed by the interplay of several
      signalling pathways that have critical functions in the regulation of cell growth
      and proliferation. Over the past years, the Hippo pathway has emerged as a key
      regulator of organ size. Perturbation of this pathway has been shown to play
      important roles in tumorigenesis. YAP, the main downstream target of the
      mammalian Hippo pathway, promotes organ growth, yet the underlying molecular
      mechanism of this regulation remains unclear. Here we provide evidence that YAP
      activates the mammalian target of rapamycin (mTOR), a major regulator of cell
      growth. We have identified the tumour suppressor PTEN, an upstream negative
      regulator of mTOR, as a critical mediator of YAP in mTOR regulation. We
      demonstrate that YAP downregulates PTEN by inducing miR-29 to inhibit PTEN
      translation. Last, we show that PI(3)K-mTOR is a pathway modulated by YAP to
      regulate cell size, tissue growth and hyperplasia. Our studies reveal a
      functional link between Hippo and PI(3)K-mTOR, providing a molecular basis for
      the coordination of these two pathways in organ size regulation.

PMID- 23143396
TI  - Selective autophagy degrades DICER and AGO2 and regulates miRNA activity.
AB  - MicroRNAs (miRNAs) form a class of short RNAs (~ 21 nucleotides) that post
      transcriptionally regulate partially complementary messenger RNAs. Each miRNA may
      target tens to hundreds of transcripts to control key biological processes.
      Although the biochemical reactions underpinning miRNA biogenesis and activity are
      relatively well defined and the importance of their homeostasis is increasingly
      evident, the processes underlying regulation of the miRNA pathway in vivo are
      still largely elusive. Autophagy, a degradative process in which cytoplasmic
      material is targeted into double-membrane vacuoles, is recognized to critically
      contribute to cellular homeostasis. Here, we show that the miRNA-processing
      enzyme, DICER (also known as DICER1), and the main miRNA effector, AGO2 (also
      known as eukaryotic translation initiation factor 2C, 2 (EIF2C2)), are targeted
      for degradation as miRNA-free entities by the selective autophagy receptor NDP52
      (also known as calcium binding and coiled-coil domain 2 (CALCOCO2)). Autophagy
      establishes a checkpoint required for continued loading of miRNA into AGO2;
      accordingly, NDP52 and autophagy are required for homeostasis and activity of the
      tested miRNAs. Autophagy also engages post-transcriptional regulation of the
      DICER mRNA, underscoring the importance of fine-tuned regulation of the miRNA
      pathway. These findings have implications for human diseases linked to
      misregulated autophagy, DICER- and miRNA-levels, including cancer.

PMID- 23143397
TI  - Coordinated oscillations in cortical actin and Ca2+ correlate with cycles of
      vesicle secretion.
AB  - The actin cortex both facilitates and hinders the exocytosis of secretory
      granules. How cells consolidate these two opposing roles was not well understood.
      Here we show that antigen activation of mast cells induces oscillations in Ca(2+)
      and PtdIns(4,5)P(2) lipid levels that in turn drive cyclic recruitment of N-WASP
      and cortical actin level oscillations. Experimental and computational analysis
      argues that vesicle fusion correlates with the observed actin and Ca(2+) level
      oscillations. A vesicle secretion cycle starts with the capture of vesicles by
      actin when cortical F-actin levels are high, followed by vesicle passage through
      the cortex when F-actin levels are low, and vesicle fusion with the plasma
      membrane when Ca(2+) levels subsequently increase. Thus, cells employ oscillating
      levels of Ca(2+), PtdIns(4,5)P(2) and cortical F-actin to increase secretion
      efficiency, explaining how the actin cortex can function as a carrier as well as
      barrier for vesicle secretion.

PMID- 23143398
TI  - MyomiR-133 regulates brown fat differentiation through Prdm16.
AB  - Brown adipose tissue (BAT) uses the chemical energy of lipids and glucose to
      produce heat, a function that can be induced by cold exposure or diet. A key
      regulator of BAT is the gene encoding PR domain containing 16 (Prdm16), whose
      expression can drive differentiation of myogenic and white fat precursors to
      brown adipocytes. Here we show that after cold exposure, the muscle-enriched
      miRNA-133 is markedly downregulated in BAT and subcutaneous white adipose tissue
      (SAT) as a result of decreased expression of its transcriptional regulator Mef2.
      miR-133 directly targets and negatively regulates PRDM16, and inhibition of miR
      133 or Mef2 promotes differentiation of precursors from BAT and SAT to mature
      brown adipocytes, thereby leading to increased mitochondrial activity. Forced
      expression of miR-133 in brown adipogenic conditions prevents the differentiation
      to brown adipocytes in both BAT and SAT precursors. Our results point to Mef2 and
      miR-133 as central upstream regulators of Prdm16 and hence of brown adipogenesis
      in response to cold exposure in BAT and SAT.

PMID- 23143399
TI  - Identification and prospective isolation of a mesothelial precursor lineage
      giving rise to smooth muscle cells and fibroblasts for mammalian internal organs,
      and their vasculature.
AB  - Fibroblasts and smooth muscle cells (FSMCs) are principal cell types of
      connective and adventitial tissues that participate in the development,
      physiology and pathology of internal organs, with incompletely defined cellular
      origins. Here, we identify and prospectively isolate from the mesothelium a mouse
      cell lineage that is committed to FSMCs. The mesothelium is an epithelial
      monolayer covering the vertebrate thoracic and abdominal cavities and internal
      organs. Time-lapse imaging and transplantation experiments reveal robust
      generation of FSMCs from the mesothelium. By targeting mesothelin (MSLN), a
      surface marker expressed on mesothelial cells, we identify and isolate precursors
      capable of clonally generating FSMCs. Using a genetic lineage tracing approach,
      we show that embryonic and adult mesothelium represents a common lineage to trunk
      FSMCs, and trunk vasculature, with minimal contributions from neural crest, or
      circulating cells. The isolation of FSMC precursors enables the examination of
      multiple aspects of smooth muscle and fibroblast biology as well as the
      prospective isolation of these precursors for potential regenerative medicine
      purposes.

PMID- 23143401
TI  - How specific is the MRI appearance of supratentorial atypical teratoid rhabdoid
      tumors?
AB  - BACKGROUND: Supratentorial atypical teratoid rhabdoid tumor (ATRT) in many cases
      has a distinctive appearance on post-gadolinium MRI. OBJECTIVE: We sought to
      determine whether this is a unique appearance allowing ATRT to be distinguished
      accurately from other types of pediatric supratentorial tumors. MATERIALS AND
      METHODS: Retrospective review of all available preoperative MRI of pediatric
      supratentorial tumors at two tertiary children's hospitals, and systematic
      literature review of case series and reports describing the MRI imaging
      appearances of supratentorial ATRT. RESULTS: We had 61 supratentorial tumors,
      including 32 gliomas, 6 ATRT, 8 ependymomas, 6 gangliogliomas, 2 pilomyxoid
      astrocytomas, 3 primitive neuro-ectodermal tumors, 2 choroid plexus papillomas,
      and 2 meningiomas. ATRT presented in significantly younger patients than
      astrocytomas (mean age 2.6 years vs. 9.9 years, P < 0.05). The visual pattern of
      a thick, wavy (irregular) heterogeneously enhancing wall around a cystic center
      was seen in 5/6 (83%) ATRTs and only 3/55 (5.4%) other tumors (P < 0.0001), for
      specificity of 95%, sensitivity of 83%, positive predictive value of 63% and a
      negative predictive value of 95%. CONCLUSION: A supratentorial tumor with a
      thick, wavy (irregular) heterogeneously enhancing wall surrounding a central
      cystic region is suggestive of ATRT in the appropriate clinical setting,
      especially in a child of preschool age.

PMID- 23143402
TI  - Imaging pediatric magnet ingestion with surgical-pathological correlation.
AB  - Foreign body ingestion is a common problem in the pediatric population and a
      frequent cause for emergency room visits. Magnets are common household objects
      that when ingested can bring about severe, possibly fatal gastrointestinal
      complications. Radiography is an integral component of the management of these
      children. Pediatric and emergency radiologists alike must be aware of imaging
      manifestations of magnet ingestion, as their identification drives decision
      making for consulting surgeons and gastroenterologists. Radiology can thus
      substantially augment the clinical history and physical exam, facilitating
      appropriate management. This manuscript sequentially presents cases of magnet
      ingestion featuring imaging findings coupled with surgical and pathological
      correlation. Each case is presented to highlight ways in which the radiologist
      can make impactful contributions to diagnosis and management. Clinical overview
      with pitfalls of magnet ingestion imaging and an imaging decision tree will also
      be presented. 

PMID- 23143403
TI  - Reply to Dr. B. Karmazyn regarding 'Duodenum between the aorta and the SMA does
      not exclude malrotation'.

PMID- 23143404
TI  - Reply to Dr. D. K. Yousefzadeh's comment on 'Sonographic assessment of the
      retroperitoneal position of the third portion of the duodenum: an indicator of
      normal intestinal rotation'.

PMID- 23143407
TI  - Transvaginal surgical treatment of cesarean scar ectopic pregnancy.
AB  - PURPOSE: To explore the feasibility of surgical management of cesarean scar
      ectopic pregnancy (CSEP) using a transvaginal approach. METHODS: Thirty-eight
      patients with CSEP presenting at the Shenzhen Nanshan People's hospital between
      January 2008 and May 2012 were reviewed in the study. Ten patients underwent
      uterine artery embolization, 13 patients underwent endoscopic CSEP removal in
      combination with chemotherapy and 15 received transvaginal surgical therapy
      (transvaginal group). Patients were followed up for between 3 and 48 months.
      RESULTS: Postoperative fever and irregular menstrual bleeding after healing were
      each observed in one of ten patients undergoing embolization. No pregnancies were
      reported in this group during follow-up. Endoscopy procedures included two
      patients undergoing laparoscopy and 11 undergoing hysteroscopy resection. There
      were six pregnancies during follow-up in this group. Transvaginal surgery was
      performed uneventfully in all cases. All patients recovered without
      complications. There were no reports of irregular menstrual bleeding or changes
      in menstrual blood volume. Serum HCG levels declined rapidly to within the normal
      range. The time to menstrual cycle recovery (29.2 +/- 5.7 days) was significantly
      shorter than with endoscopic surgery (37.6 +/- 8.2 days) or embolization (64.4 +/
      9.2 days; P < 0.05). Three patients became pregnant after transvaginal surgery.
      CONCLUSION: Transvaginal removal of ectopic pregnancy tissue is a new surgical
      approach for the treatment of CSEP. The efficacy and safety of the approach needs
      further confirmation.

PMID- 23143406
TI  - Major histocompatibility complex class II deficiency in Kuwait: clinical
      manifestations, immunological findings and molecular profile.
AB  - Major Histocompatibility Complex (MHC) class II deficiency is a combined primary
      immunodeficiency disease that leads to overwhelming and recurrent infections. It
      was found to account for 19 % of combined immune deficiency cases in the National
      Primary Immunodeficiency Disorders Registry in Kuwait, a country with high
      prevalence of consanguinity. We present the clinical, immunologic and molecular
      features of 11 Kuwaiti patients who presented with MHC class II deficiency
      between 2004 and 2011.

PMID- 23143408
TI  - Does mode of delivery affect neonate oxidative stress in parturition? Review of
      literature.
AB  - PURPOSE: The production of reactive oxygen substances plays an important
      regulatory role in many physiologic reproductive processes. Excessive production
      may lead to oxidative stress (OS), and bring about pregnancy disorders. Growing
      evidence indicates that OS plays a major role in the pathophysiology of
      complications such as early pregnancy loss, placental insufficiency,
      preeclampsia, fetal growth restriction, and neonatal complications. Whether
      parturition induces oxidative stress is in dispute. In this review, we elaborate
      the influence of mode of delivery (vaginal delivery or cesarean delivery) on
      oxidative stress of neonates. METHODS: A review of old and recent literature was
      done. The studies were divided according to the impact of mode of delivery on
      oxidative stress in the newborn. RESULTS: There is a divergence in the oxidative
      stress production according to the mode of delivery. CONCLUSIONS: In view of
      neonatal oxidative stress measures, no major difference was found between
      uncomplicated vaginal delivery and elective cesarean section.

PMID- 23143409
TI  - A lost LNG-IUP in the bladder.

PMID- 23143410
TI  - Tranexamic acid for cesarean section: a double-blind, placebo-controlled,
      randomized clinical trial.
AB  - PURPOSE: To assess the efficacy and safety of an intravenous formulation of
      tranexamic acid to reduce intrapartum and postpartum bleeding in patients giving
      birth by cesarean section. METHODS: Healthy women with normal pregnancies, at any
      gestational age, that we performed ceaserean section. Two hundred and twenty
      three patients with cesarean section, were enrolled in a double-blind, placebo
      controlled study. Tranexamic acid of 20 cc and a 20 cc 5 % dextrose solution was
      intravenously injected to the patients; both the study group (n = 101) and the
      control group (n = 122) 10 min before the start of cesarean section. We measured
      volume of blood loss in postoperative periods, decrease in hemoglobin and
      hematocrit levels after cesarean section. The mean follow up was 2 weeks after
      the operation. RESULTS: Tranexamic acid reduced intraoperative and postoperative
      blood loss. We did not observe any complications caused by TA such as venous
      thromboembolism, gastrointestinal problems and hypersensitivity. CONCLUSIONS:
      This study confirms that tranexamic acid is effective in reducing intrapartum and
      postpartum bleeding in patients giving birth by cesarean section. Although some
      obstetricians are still worried about its thrombosis risk, our study shows that
      it can be used safely in aforementioned patients.

PMID- 23143411
TI  - Effects of quetiapine extended release on sleep and quality of life in midlife
      women with major depressive disorder.
AB  - Depression during midlife years may lead to significant sleep disturbances and
      adversely impact quality of life (QOL). In this report, we examined the effects
      of treatment with quetiapine extended release (XR), 150-300 mg/day, on sleep and
      QOL in 23 midlife women with major depressive disorder (MDD). Quetiapine XR
      improved subjective sleep distress, overall sleep parameters, and sleep-related
      QOL, ultimately leading to significant improvement in menopause-related QOL.
      While larger, controlled trials are still awaited, these preliminary results are
      encouraging and suggest that quetiapine XR may be a useful tool in treating
      symptomatic midlife women with MDD.

PMID- 23143412
TI  - Alternate copies of D1 are used by cyanobacteria under different environmental
      conditions.
AB  - All cyanobacteria sequenced to date have multiple psbA genes, encoding the D1
      protein. Some of these psbA genes have a series of mutations that would seem to
      render D1 incapable of binding the Mn(4)CaO(5) metallocluster (Murray, Photosynth
      Res 110(3):177-184, 2012). Nonetheless, these genes are expressed under specific
      environmental conditions, such as during N(2) fixation in unicellular diazotrophs
      of the genes Cyanothece. These genes emphasize the clever way that cyanobacteria
      have learned to deal with a constantly changing environment.

PMID- 23143413
TI  - Structure and function of a unique pore-forming protein from a pathogenic
      acanthamoeba.
AB  - Human pathogens often produce soluble protein toxins that generate pores inside
      membranes, resulting in the death of target cells and tissue damage. In
      pathogenic amoebae, this has been exemplified with amoebapores of the enteric
      protozoan parasite Entamoeba histolytica. Here we characterize acanthaporin, to
      our knowledge the first pore-forming toxin to be described from acanthamoebae,
      which are free-living, bacteria-feeding, unicellular organisms that are
      opportunistic pathogens of increasing importance and cause severe and often fatal
      diseases. We isolated acanthaporin from extracts of virulent Acanthamoeba
      culbertsoni by tracking its pore-forming activity, molecularly cloned the gene of
      its precursor and recombinantly expressed the mature protein in bacteria.
      Acanthaporin was cytotoxic for human neuronal cells and exerted antimicrobial
      activity against a variety of bacterial strains by permeabilizing their
      membranes. The tertiary structures of acanthaporin's active monomeric form and
      inactive dimeric form, both solved by NMR spectroscopy, revealed a currently
      unknown protein fold and a pH-dependent trigger mechanism of activation.

PMID- 23143414
TI  - Identification of DES1 as a vitamin A isomerase in Muller glial cells of the
      retina.
AB  - Absorption of a light particle by an opsin-pigment causes photoisomerization of
      its retinaldehyde chromophore. Restoration of light sensitivity to the resulting
      apo-opsin requires chemical re-isomerization of the photobleached chromophore.
      This is carried out by a multistep enzyme pathway called the visual cycle.
      Accumulating evidence suggests the existence of an alternative visual cycle for
      regenerating opsins in daylight. Here we identified dihydroceramide desaturase-1
      (DES1) as a retinol isomerase and an excellent candidate for isomerase-2 in this
      alternative pathway. DES1 is expressed in retinal Muller cells, where it
      coimmunoprecipitates with cellular retinaldehyde binding protein (CRALBP).
      Adenoviral gene therapy with DES1 partially rescued the biochemical and
      physiological phenotypes in Rpe65(-/-) mice lacking isomerohydrolase (isomerase
      1). Knockdown of DES1 expression by RNA interference concordantly reduced
      isomerase-2 activity in cultured Muller cells. Purified DES1 had very high
      isomerase-2 activity in the presence of appropriate cofactors, suggesting that
      DES1 by itself is sufficient for isomerase activity.

PMID- 23143415
TI  - O2-independent formation of the inactive states of NiFe hydrogenase.
AB  - We studied the mechanism of aerobic inactivation of Desulfovibrio fructosovorans
      nickel-iron (NiFe) hydrogenase by quantitatively examining the results of
      electrochemistry, EPR and FTIR experiments. They suggest that, contrary to the
      commonly accepted mechanism, the attacking O(2) is not incorporated as an active
      site ligand but, rather, acts as an electron acceptor. Our findings offer new
      ways toward the understanding of O(2) inactivation and O(2) tolerance in NiFe
      hydrogenases.

PMID- 23143416
TI  - Active site profiling reveals coupling between domains in SRC-family kinases.
AB  - Protein kinases, key regulators of intracellular signal transduction, have
      emerged as an important class of drug targets. Chemical proteomic tools that
      facilitate the functional interrogation of protein kinase active sites are
      powerful reagents for studying the regulation of this large enzyme family and
      performing inhibitor selectivity screens. Here we describe a new crosslinking
      strategy that enables rapid and quantitative profiling of protein kinase active
      sites in lysates and live cells. Applying this methodology to the SRC-family
      kinases (SFKs) SRC and HCK led to the identification of a series of conformation
      specific, ATP-competitive inhibitors that have a distinct preference for the
      autoinhibited forms of these kinases. Furthermore, we show that ligands that have
      this selectivity are able to modulate the ability of the regulatory domains of
      SRC and HCK to engage in intermolecular binding interactions. These studies
      provide insight into the regulation of this important family of tyrosine kinases.

PMID- 23143417
TI  - Challenges to protocol optimization due to unexpected variation of CT contrast
      dose amount and flow.
AB  - High-quality computed tomography (CT) exams are critical to maximizing
      radiologist's interpretive ability. Exam quality in part depends on proper
      contrast administration. We examined injector data from consecutive abdominal and
      pelvic CT exams to analyze variation in contrast administration. Discrepancies
      between intended IV contrast dose and flow rate with the actual administered
      contrast dose and measured flow rate were common. In particular, delivered
      contrast dose discrepancies of at least 10% occurred in 13% of exams while
      discrepancies in flow rate of at least 10% occurred in 42% of exams. Injector
      logs are useful for assessing and tracking this type of variability which may
      confound contrast administration optimization and standardization efforts.

PMID- 23143418
TI  - Does varus alignment increase after medial meniscectomy?
AB  - PURPOSE: In patients who underwent arthroscopic meniscectomy for medial meniscus
      tears, the authors wished to ascertain (1) whether varus alignment in the lower
      extremity would increase after an operation and (2) if so, what the related
      factors would be. METHODS: Among 181 patients from 20 to 60 years of age who
      underwent arthroscopic medial meniscectomy for medial meniscus tears between 2002
      and 2005, 56 patients followed for a minimum period of 5 years were enroled for
      this study. Alignment in the lower extremity was measured preoperatively and
      again at the last follow-up. Change in varus alignment (the difference between
      preoperative alignment and alignment at the last follow-up) was analyzed in
      relation to sex, age, body mass index (BMI), resection amount (partial vs.
      total), preoperative alignment, and follow-up duration, using multiple linear
      regression analysis. RESULTS: Varus deformity increased by 1.7 degrees  +/- 1.5
      degrees  from a preoperative mean of 2.4 degrees  +/- 2.4 degrees  to a mean of
      4.1 degrees  +/- 3.0 degrees  at the last follow-up, which was statistically
      significant (p = 0.000). From multiple linear regression analysis, only the
      resection amount (partial meniscectomy or total meniscectomy) was found to be
      significantly related to the change in varus alignment (p = 0.002). Other factors
      including sex, age, BMI, preoperative alignment, presence of cartilage injury and
      follow-up duration were not significantly related to the change in varus
      alignment after the operation. CONCLUSIONS: Arthroscopic meniscectomy performed
      in patients with medial meniscus tears aggravated varus alignment in the lower
      extremity at the last follow-up. In addition, the increase in varus deformity was
      significantly higher among patients with total meniscectomy than among those with
      partial meniscectomy. LEVEL OF EVIDENCE: Retrospective comparative study, level
      III.

PMID- 23143419
TI  - Partial lateral facetectomy plus Insall's procedure for the treatment of isolated
      patellofemoral osteoarthritis: survival analysis.
AB  - PURPOSE: The purpose of this study was to report the survival analysis of partial
      lateral facetectomy and Insall's procedure in patients with isolated
      patellofemoral osteoarthritis, and to assess the risk and protective factors for
      failure of this procedure. METHODS: From 1992 to 2004, all subjects with isolated
      patellofemoral osteoarthritis who met the inclusion criteria and underwent this
      procedure were enrolled. Risk and protective factors for failure (failure
      considered as the need for total knee arthroplasty) were assessed by comparing
      obtained baseline data between failed and non-failed cases. Eighty-seven cases
      (mean (SD) age 61.8 (7.7) years, mean (SD) follow-up 9.6 (3.2) years) were
      included. RESULTS: Twenty-three failed cases were found. Mean (SD) survival time
      was 13.6 (0.5) years. At 13 years (last failure case), the cumulative survival
      was 59.3 %. Baseline medial tibiofemoral pain, genu flexum, and worst grade of
      tibiofemoral osteoarthritis were significant risk factors for failure (p <
      0.0001, p = 0.02, p < 0.0001, respectively). In contrast, higher anatomical (p =
      0.02) and total (p = 0.03) knee society score (KSS) scores, absence of knee
      effusion (p = 0.03), higher value of the Caton-Deschamps index (p = 0.03), and
      lateral position of the patella (p = 0.01) were all protective factors against
      failure. CONCLUSION: The treatment for isolated patellofemoral osteoarthritis
      through partial lateral facetectomy and Insall's procedure demonstrated good long
      term survival. The presence of preoperative medial tibiofemoral pain, genu
      flexum, and incipient tibiofemoral osteoarthritis increased the risk of failure
      of this procedure. In contrast, higher anatomical and total KSS scores, absence
      of knee effusion, higher value of the Caton-Deschamps index, and lateral position
      of the patella were found to protect against failure.

PMID- 23143420
TI  - Cosmetic vaginal surgery:  the role of the female pelvic surgeon.

PMID- 23143421
TI  - Apical vaginal prolapse surgery:  practice patterns and factors guiding route of
      repair.
AB  - OBJECTIVES: Describe current trends for repair of primary and recurrent apical
      vaginal prolapse using 4 different approaches, namely, transvaginal native (TVN)
      tissue, transvaginal using graft, laparotomy, or laparoscopic/robotic, and to
      determine which factors influence decision for favored approach. METHODS: A 15
      item survey was distributed to attendees of the 2011 Society of Gynecologic
      Surgeons meeting. Demographic data and percentages of routes of repair were
      collected. Twenty factors were graded on the importance for influencing surgical
      approach. RESULTS: Transvaginal native tissue was the preferred route for primary
      repair (mean, 53.0%), and laparoscopic/robotic for recurrent repair (33.8%).
      Surgeons in academic practices, without formal postresidency training, and with
      lower surgical volumes were more likely to elect TVN for primary repair than
      alternatives. Important factors in selection of surgical approach included
      patient age and severity of medical comorbidities. CONCLUSIONS: Among the Society
      of Gynecologic Surgeons meeting attendees, TVN is the preferred primary route for
      apical prolapse repair. Laparoscopic-assisted repairs are more common for
      recurrent prolapse.

PMID- 23143422
TI  - Intraoperative and postoperative gastrointestinal complications associated with
      laparoscopic sacrocolpopexy.
AB  - OBJECTIVE: This study aimed to quantify the risks of intraoperative and
      postoperative gastrointestinal (GI) complications associated with laparoscopic
      sacrocolpopexy and identify possible risk factors. METHODS: A total of 390
      medical records were retrospectively reviewed for GI complications. Complications
      were classified as functional complications [ileus, small bowel obstruction
      (SBO), and prolonged nausea/emesis] or bowel injury. Nausea/emesis was considered
      prolonged if these symptoms resulted in a hospital stay of greater than 48 hours,
      or in readmission. RESULTS: Functional GI complications included 1 ileus, 3 SBOs,
      and 3 cases of prolonged nausea/emesis. The combined rate for ileus and SBO was
      1.0% and the rate of prolonged nausea/emesis was 0.8%. Functional GI
      complications were associated with prior abdominal surgery (P = 0.048), but there
      were no differences in age, body mass index, estimated blood loss, or operative
      time.There were 3 small bowel and 2 rectal injuries for a bowel injury rate of
      1.3%. Bowel injury was not associated with prior abdominal surgery (P = 0.071),
      age, body mass index, estimated blood loss, or operative time. The total
      reoperation rate for SBO or bowel injury was 0.8%. CONCLUSIONS: The rates of GI
      complications in laparoscopic sacrocolpopexy are low. Prior abdominal surgery was
      associated with an increased risk of functional GI complications, but not bowel
      injury. This information should assist surgeons with preoperative patient
      counseling.

PMID- 23143423
TI  - Age effects on pelvic floor symptoms in a cohort of nulliparous patients.
AB  - OBJECTIVES: This study aimed to investigate the effects of age on pelvic floor
      symptoms (PFSs) in nulliparous women. METHODS: Eighty community-dwelling
      nulliparous women, aged 21 to 70 years, were recruited. Pelvic floor support was
      assessed with pelvic organ prolapse quantification system. Participants completed
      the Pelvic Floor Distress Inventory 20 and Pelvic Floor Impact Questionnaire 7.
      Sexual function was assessed with the Pelvic Organ Prolapse/Urinary Incontinence
      Sexual Function Questionnaire 12 and health status with the Short-Form Health
      Survey. The correlation between age and questionnaire scores was evaluated using
      Pearson coefficient. Logistic regression assessed predictors associated with PFS.
      RESULTS: Participants had a median age of 47 years, average body mass index of
      28.3 kg/m, and most were white; 52.5% were healthy and 30% were postmenopausal.
      The most common stage of prolapse was stage I.Age was associated with slightly
      higher Pelvic Floor Distress Inventory-20 scores (r = 0.41, P = 0.002),
      corresponding to more bothersome PFS, and lower Pelvic Organ Prolapse/Urinary
      Incontinence Sexual Function Questionnaire-12 scores, corresponding to worsening
      sexual function with advancing age (r = -0.41, P = 0.0012). There was no
      association between age and overall Pelvic Floor Impact Questionnaire scores (P =
      0.12). For symptomatic patients, logistic regression showed age to be associated
      with increased odds of having PFS [odds ratio (OR), 1.881; 95% confidence
      interval (CI), 1.216-2.91]. Menopausal status was not associated with increased
      odds of reporting symptoms (OR, 3.05; 95% CI, 0.80-11.62). When age and age by
      menopause were incorporated in the model, age remained a significant predictor of
      having PFS (OR, 1.78; 95% CI, 1.13-2.78). CONCLUSIONS: In this population of
      community-dwelling nulliparous women, age was associated with worsening sexual
      function and slightly increased odds of reporting symptoms of pelvic floor
      disorders.

PMID- 23143424
TI  - Validation of Hebrew versions of the Pelvic Floor Distress Inventory, Pelvic
      Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire, and the
      Urgency, Severity and Impact Questionnaire.
AB  - OBJECTIVE: Validated objective tools in the native languages of investigated
      populations are important for evaluating effects of medical disorders and
      treatments. The aim of our study was to validate a Hebrew version of the
      validated questionnaires commonly used in the field of urogynecology. METHODS:
      This is a 2-step, prospective, multicenter study. Using a back-translation
      method, Hebrew-language versions of the following questionnaires were developed:
      Pelvic Floor Distress Inventory, Pelvic Organ Prolapse/Urinary Incontinence
      Sexual Function Questionnaire, and the Urgency, Severity and Impact
      Questionnaire. The questionnaires were administered in both Hebrew and English to
      56 bilingual patients with pelvic organ prolapse and/or urinary incontinence. To
      test reliability, the participants were asked to refill the questionnaires in
      Hebrew 2 weeks later. Scores from the Hebrew and English versions were compared,
      using the Wilcoxon signed rank test. Correlations between versions were assessed
      by the Spearman test. P < 0.05 or less was considered significant. RESULTS:
      Scores from the Hebrew and English versions were found to be highly correlated,
      rho = 0.61-0.96; P < 0.001. No differences in total scores were detected between
      the 2 versions of the 3 questionnaires and their subcategories (P > 0.05).
      Cronbach alpha values were good (0.65-096) for all questionnaires. Scores were
      highly correlated when the patients refilled the questionnaires in Hebrew (rho =
      0.81-0.98; P < 0.001). CONCLUSIONS: This study provides validated Hebrew versions
      of 3 well-accepted pelvic floor questionnaires. These questionnaires will enable
      standardization when assessing women with pelvic floor dysfunction.

PMID- 23143425
TI  - Analysis of the impact of obesity on recurrence rates of stress urinary
      incontinence after urethrolysis or sling revision.
AB  - OBJECTIVE: The impact of obesity on the recurrence rates of stress urinary
      incontinence (SUI) after urethrolysis/sling revision was analyzed. STUDY DESIGN:
      A retrospective analysis was conducted of patients who underwent urethrolysis or
      sling revision from January 2004 to November 2010. RESULTS: Data from 74 patients
      were included. The mean body mass index (BMI) was 29.8 kg/m (SD, 6.3) and 37/74
      (50%) women were obese (BMI >= 30 kg/m) with a mean length of follow-up of 27
      weeks (range, 6-132 weeks). The following urethrolysis/sling revision surgical
      techniques were varied: partial transvaginal urethrolysis, complete transvaginal
      urethrolysis, abdominal urethrolysis, sling transection, and transvaginal sling
      stretching.Of the 74 cases, 25 (33.8%) had recurrent SUI after urethrolysis or
      sling revision. The BMI did not differ between those who did and did not have a
      recurrence (t test P = 0.68); 25/49 (51%) women who did not have a recurrence
      were obese and 12/25 (48%) women with recurrence were obese. CONCLUSIONS: Obesity
      was not associated with increased rates of SUI recurrence after
      urethrolysis/sling revision.

PMID- 23143426
TI  - Cost analysis of open versus robotic-assisted sacrocolpopexy.
AB  - OBJECTIVE: This study aimed to report on the costs, operative times, and length
      of stay for robotic and open sacrocolpopexy. STUDY DESIGN: This retrospective
      study compares consecutive open and robotic sacrocolpopexies that were performed
      beyond the surgical learning curve. Hospital direct costs, operative times, and
      length of stay were compared for the 2 groups. Robot cost and maintenance were
      included. Statistical significance was considered at P < 0.05. RESULTS: The study
      comprised 91 open and 73 robotic sacrocolpopexies. Both groups were similar
      clinically. Median operative times for open and robotic approaches were 166 and
      212 minutes (P < 0.001), respectively, and length of stay was 3 versus 2 days (P
      < 0.001). Of the women in the robotic group, 48% had length of stay less than 24
      hours versus 1% in the open group. Median robotic and open procedure direct costs
      were $6668 and $7804 (P = 0.002), respectively. Readmission rates at 30 days
      postoperatively were similar. CONCLUSIONS: Robotic sacrocolpopexy costs less but
      takes slightly longer to perform than the open procedure.

PMID- 23143427
TI  - Health literacy and disease understanding among aging women with pelvic floor
      disorders.
AB  - OBJECTIVES: Few studies on health literacy and disease understanding among women
      with pelvic floor disorders have been published. We conducted a pilot study to
      explore the relationship between disease understanding and health literacy, age,
      and diagnosis type among women with urinary incontinence and pelvic organ
      prolapse. METHODS: The study subjects were recruited from urology and
      urogynecology specialty clinics based on a chief complaint suggestive of urinary
      incontinence or pelvic prolapse. Subjects completed questionnaires to assess
      symptom severity, and health literacy was measured using the Test of Functional
      Health Literacy in Adults. Patient-physician interactions were audiotaped during
      the office visit. Immediately afterward, patients were asked to describe
      diagnoses and treatments discussed by the physician and record them on a
      checklist, with follow-up phone call, where the same checklist was administered 2
      to 3 days later. RESULTS: A total of 36 women with pelvic floor disorders, aged
      42 to 94 years, were enrolled. We found that health literacy scores decreased
      with increasing age. However, all patients had low percentage recall of their
      pelvic floor diagnoses and poor understanding of their pelvic floor condition
      despite high health literacy scores. Patients with pelvic prolapse seemed to have
      worse recall and disease understanding than patients with urinary incontinence.
      CONCLUSIONS: High health literacy as assessed by the Test of Functional Health
      Literacy in Adults may not correlate with patients' ability to comprehend complex
      functional conditions such as pelvic floor disorders. Lack of understanding may
      lead to unrealistic treatment expectations, inability to give informed consent
      for treatment, and dissatisfaction with care. Better methods to improve disease
      understanding are needed.

PMID- 23143428
TI  - Do symptoms of voiding dysfunction predict urinary retention?
AB  - OBJECTIVES: We assessed the relationship between symptoms of voiding dysfunction
      and elevated postvoid urinary residual (PVR). METHODS: Cross-sectional study of
      women presenting for initial evaluation from February through July 2011. Charts
      were reviewed for demographics, voiding dysfunction symptoms, and examination
      findings. Urinary retention was defined as PVR of 100 ml or more. Data are
      presented as median (interquartile range) or proportion; test characteristics are
      reported with 95% confidence intervals. RESULTS: Of 641 eligible women, 57 women
      (8.9%) had urinary retention. Of these, 32 women (56.1%) had at least one symptom
      of voiding dysfunction, most commonly, sensation of incomplete emptying (30.1%).
      Sensitivity and positive predictive values of voiding dysfunction symptoms were
      low. Of 254 women reporting voiding symptoms, most (87.5%) had PVR of less than
      100 ml and were significantly more likely to have other pelvic floor symptoms and
      findings. CONCLUSIONS: Patients' symptoms do not predict urinary retention.
      Postvoid urinary residual should be measured, and other causes of voiding
      dysfunction symptoms should be considered.

PMID- 23143429
TI  - Routine use of preoperative cystourethroscopy on the surgical management of
      urinary incontinence and pelvic organ prolapse.
AB  - OBJECTIVES: To determine the impact of routine preoperative cystourethroscopy on
      the surgical management of urinary incontinence and pelvic organ prolapse.
      METHODS: Retrospective review of consecutive women undergoing surgery for urinary
      incontinence and/or pelvic organ prolapse at a tertiary referral urogynecology
      center to determine whether the routine use of preoperative cystourethroscopy
      changed the surgical management. Patients with other indications for
      cystourethroscopy were excluded. RESULTS: A total of 283 consecutive charts were
      reviewed of which 235 met inclusion criteria. Five patients accounted for 6
      abnormal findings on preoperative cystourethroscopic examination including 2
      bladder calculi, 2 lesions suspicious for neoplasm, and 2 cases of absent
      unilateral ureteric efflux. In only one case (0.5%) was the surgical plan
      altered. CONCLUSION: The routine use of preoperative cystourethroscopy in low
      risk patients being prepared for surgery for urinary incontinence and pelvic
      prolapse is not required when no other indications for cystourethroscopy exist.

PMID- 23143430
TI  - Informed consent for sacrocolpopexy:  is counseling effective in achieving
      patient comprehension?
AB  - OBJECTIVES: The purpose of the informed consent process is to reinforce a
      patient's understanding of her condition and treatment alternatives and to
      thoroughly review the chosen procedure with its risks and benefits. We aimed to
      evaluate how well women who consented to undergo sacrocolpopexy understood their
      planned procedure. STUDY DESIGN: We prospectively studied women who had undergone
      detailed informed consent in preparation for laparoscopic or robotic
      sacrocolpopexy. A 15-item questionnaire was developed and administered before
      surgery to assess the patients' comprehension of preoperative counseling.
      RESULTS: Fifty women were enrolled. The mean knowledge score was 69.7%. Sixty
      four percent of the patients did not recall that they could have a prolapse
      repair without mesh, 44% did not understand the location of mesh attachment, and
      34% believed there was no risk of recurrent prolapse. Women who completed the
      questionnaire within 3 weeks of signing the surgical consent had a higher mean
      score (78.5%) than women for whom 3 or more weeks elapsed (66.3%; P=0.02).
      CONCLUSION: Despite detailed preoperative discussion, women had deficiencies in
      their understanding of sacrocolpopexy. New methods to improve patient education
      and comprehension should be considered.

PMID- 23143431
TI  - Risk factors for mesh extrusion after prolapse surgery:  a case-control study.
AB  - OBJECTIVES: To identify risk factors for mesh extrusion in women undergoing
      pelvic organ prolapse repair by abdominal sacral colpopexy (ASC) or vaginal mesh
      procedure (VMP). METHODS: A multicenter case-control study of patients who
      underwent ASC or VMP from 2006 to 2009 identified using diagnosis and procedure
      coding. Cases were defined as women who underwent eligible index procedure with
      synthetic mesh and had mesh visible through the vaginal epithelium at
      postoperative evaluation; controls were matched in an approximate 1:3 ratio by
      date and type of procedure. Two conditional logistic regression models were
      constructed to assess variables associated with mesh extrusion among women who
      underwent ASC and among women who underwent VMP. RESULTS: Eighty-four cases were
      identified (43 cases after ASC and 41 cases after VMP), and 252 patients were
      matched as controls (147 patients who underwent ASC and 105 patients who
      underwent VMP). Concomitant hysterectomy was positively associated with mesh
      extrusion) among women who underwent ASC (adjusted odds ratio, 3.18; 95%
      confidence interval, 1.27-7.93; P = 0.01) and VMP (adjusted odds ratio, 3.72, 95%
      confidence interval, 1.20-11.54; P = 0.02). Age, race, type of vaginal incision,
      menopausal status, medical comorbidities, and smoking were not significantly
      associated with extrusion in either group. CONCLUSIONS: Concomitant hysterectomy
      is a risk factor for mesh extrusion after ASC and VMPs. This information may be
      helpful during informed preoperative counseling and planning.

PMID- 23143432
TI  - Commonalities of cerclage-related genitourinary fistulas.
AB  - OBJECTIVES: The purpose of this review was to identify common features of
      cerclage-related genitourinary fistulas. METHODS: A retrospective case series of
      cerclage-related fistulas was performed. The results were then pooled with
      available published case reports to identify common factors in these cases.
      Fistula location, surgical technique, and previous surgical and obstetrical
      histories were examined. RESULTS: From 2008 to 2011, 5 women were referred with
      vesicovaginal fistulas after cerclage. Within this series, 4 had prior cervical
      procedures, 3 had previous cesarean deliveries, and 4 had a McDonald cerclage in
      the antecedent pregnancy. When pooled with available data in 7 published case
      reports on cerclage-related fistulas, all 12 fistulas occurred in patients with
      prior histories of cervical procedures or cesarean deliveries. Specifically, of
      the 12 patients, 8 [66.7%; 95% confidence interval (CI), 0.39-0.86] had at least
      1 prior cerclage and 10 (83.3%; 95% CI, 0.54-0.97) had at least 1 prior cervical
      surgery. When reported, 81.8% (95% CI, 0.51-0.96) had the McDonald technique used
      for placement of the current cerclage. CONCLUSIONS: The isolated and pooled
      findings suggest previous cerclage, any previous cervical procedures, and use of
      the McDonald technique are common factors in cases of cerclage-related
      genitourinary fistulas. This information may be useful when evaluating and
      counseling patients.

PMID- 23143433
TI  - Complex rectovaginal fistulas after pelvic organ prolapse repair with synthetic
      mesh:  a multidisciplinary approach to evaluation and management.
AB  - OBJECTIVES: The use of synthetic mesh for transvaginal pelvic organ prolapse
      (POP) repair is associated with the rare complication of mesh erosion into hollow
      viscera. This study presents a single-institution series of complex rectovaginal
      fistulas (RVFs) after synthetic mesh-augmented POP repair, as well as strategies
      for identification and management. METHODS: Institutional review board approval
      was obtained for this retrospective study. Data were collected and analyzed on
      all female patients undergoing RVF repair from 2000 to 2011 at our institution.
      RESULTS: Thirty-seven patients underwent RVF repair at our multidisciplinary
      center for restorative pelvic medicine. Of these, 10 (27.0%) were associated with
      POP repairs using mesh. The POP repairs resulting in RVF were transvaginal repair
      with mesh (n = 8), laparoscopic sacrocolpopexy with concomitant traditional
      posterior repair (n = 1), and robotic-assisted laparoscopic sacrocolpopexy (n =
      1). Time to presentation was an average of 7.1 months after POP repair. Patients
      underwent a mean of 4.4 surgeries for definitive RVF repair, with 40% of patients
      requiring a bowel diversion (3 temporary ileostomies and 1 long-term colostomy).
      Mean follow-up time after last surgery was 9.2 months. On follow-up, 1 patient
      has a persistent fistula with vaginal mesh extrusion. One patient has persistent
      pelvic pain. CONCLUSIONS: This series highlights the significant impact of
      synthetic mesh complications in the posterior compartment. These complications
      should be cautionary for synthetic graft use by those with limited experience,
      particularly when an alternate choice of traditional repair is available. When
      symptoms of RVF are present, collaboration with a colon and rectal specialist
      should be initiated as soon as possible for evaluation and definitive repair.

PMID- 23143434
TI  - Failed omental flap vesicovaginal fistula repair subsequently repaired
      laparoscopically without an omental flap.
AB  - BACKGROUND: Conventional wisdom suggests that vascular interposition flaps are
      helpful in the treatment of all patients with vesicovaginal fistulas. Complicated
      fistulas are often treated with interposition omental flaps; however, failed
      omental flap repairs have not been described without the use of another
      interposition flap. CASE: A 52-year-old woman with a history of cystotomy repair
      at the time of hysterectomy and a subsequent abdominal omental flap vesicovaginal
      fistula repair failure underwent a successful repair using a laparoscopic-layered
      closure of her fistula without omental flap. CONCLUSION: A failed omental flap
      vesicovaginal fistula repair can be repaired laparoscopically and without an
      omental flap.

PMID- 23143435
TI  - Vesicovaginal fistula due to remote history of vaginal foreign body.
AB  - OBJECTIVES: To report an interesting case of a young adult girl who developed a
      vesicovaginal fistula after removal of a vaginal foreign body. METHODS: A chart
      review was performed for a single patient from the time of presentation in July
      2010 until final follow-up encounter. RESULTS: A 22-year-old nulliparous woman
      with a history of removal of a bottle cap from her vagina developed a large
      vesicovaginal fistula at the bladder neck, which was identified several years
      later. Closure was via vaginal approach without graft or flap interposition.
      CONCLUSIONS: Although fistula formation after foreign body identification is
      rare, early identification and appropriate surgical approach is important for
      improved patient outcomes.

PMID- 23143436
TI  - Retroperitoneal duplication cyst with a fistulous tract to the vagina:  a case
      report.
AB  - OBJECTIVES: To describe a rare case of a retroperitoneal duplication cyst that
      fistulized to the vagina. METHODS: Case description and discussion of a patient
      found to have an intestinal duplication cyst. RESULTS: A patient presented for a
      laparoscopic hysterectomy because of menorrhagia and a fibroid uterus. She also
      complained of recurrent urinary tract infections (UTIs) and a vaginal discharge.
      A retroperitoneal intestinal duplication cyst that fistulized to the vagina and
      caused her recurrent UTIs was identified. Surgical resection of the cyst resolved
      her complaint of recurrent UTIs. CONCLUSIONS: Retroperitoneal intestinal
      duplication cysts are rare congenital anomalies with vague clinical
      manifestations. The finding of a fistulous communication to the vagina
      originating from such a structure can be associated with recurrent UTIs.

PMID- 23143439
TI  - Subjective quality of vision before and after cataract surgery.
AB  - OBJECTIVE: To investigate the effect of cataract surgery on subjective quality of
      vision. METHODS: The Quality of Vision (QoV) questionnaire (Italian translation)
      was completed before and 3 months after cataract surgery in 4 groups of patients
      recruited from September through December 2010: first eye with ocular
      comorbidity, first eye without ocular comorbidity, second eye with ocular
      comorbidity, and second eye without ocular comorbidity. The questionnaire
      measures 3 aspects of quality of vision: frequency, severity, and bothersome
      nature of symptoms. The Lens Opacities Classification System (LOCS) III was used
      for cataract grading. Friedman and Kruskal-Wallis H tests were performed to
      compare QoV scores within and between groups. Spearman rank correlations (rs)
      were calculated to investigate the correlation between LOCS III and QoV symptoms.
      RESULTS: Two hundred twelve patients (mean [SD] age, 74.2 [8.7] years) were
      recruited, and 212 eyes were included in the study. Improvements in QoV scores
      were found in all 4 groups (P < .05). There were no statistically significant (P
      > .05) differences among the 4 groups in the improvement in QoV scores or in the
      preoperative or postoperative scores. Blurred vision was correlated with
      posterior subcapsular cataract (rs = 0.420, P = .04). CONCLUSIONS: Cataract in
      one or both eyes causes a similar loss in subjective quality of vision, which is
      also irrespective of the presence of ocular comorbidity. Posterior subcapsular
      cataract causes the specific symptom "blurred vision." Cataract surgery resulted
      in a large and comparable improvement in subjective quality of vision, regardless
      of ocular comorbidity and first or second eye surgery.

PMID- 23143440
TI  - Chlorpromazine-induced corneal toxicity.

PMID- 23143437
TI  - Targeting multidrug-resistant tuberculosis (MDR-TB) by therapeutic vaccines.
AB  - Tuberculosis (TB) has scourged humankind for millennia, and latent infection
      affects nearly one-third of today's world population. The emergence of multidrug
      resistant (MDR)-TB is a major global threat and reflects treatment failure of
      drug-sensitive disease. MDR-TB management is a burden for patients and society;
      success rates are unacceptably low with prolonged treatment duration.
      Mycobacterium tuberculosis (Mtb) possesses the ability to transform into a
      dormant state in which it can persist in the face of antimicrobial treatment and
      host defense. This sub-population of persisters is largely responsible for
      lengthy and difficult treatment. Targeting persistent bacilli could eventually
      improve the treatment success rate (currently 50-65 %) and shorten duration of
      treatment. A subset of therapies in the pipeline, termed therapeutic vaccines,
      use the host immune response to attack Mtb. The historical occurrence of an
      exacerbated host response has resulted in a negative perception of therapeutic
      vaccines. Thus, a renewed concept of immunotherapy is needed. We review current
      perspectives of immunotherapy in MDR-TB based on the knowledge of TB immunology
      and briefly discuss the profiles of several therapeutic vaccine products.

PMID- 23143441
TI  - Swedish national register for retinopathy of prematurity (SWEDROP) and the
      evaluation of screening in Sweden.
AB  - OBJECTIVES: To evaluate screening for retinopathy of prematurity (ROP) in Sweden
      and to investigate possible modifications of the present screening guidelines.
      METHODS: Infants in Sweden with a gestational age (GA) of 31 weeks + 6 days or
      less are screened for ROP. Data from the Swedish national register for ROP
      (SWEDROP) during 2008 and 2009 were extracted and compared with a national
      perinatal quality register. RESULTS: In SWEDROP, there were 1791 infants born
      before a GA of 32 weeks from January 1, 2008, through December 31, 2009. Another
      70 infants were registered in the perinatal quality register but not in SWEDROP
      (dropout rate, 3.8% [70 of 1861 infants]). Seven infants died before termination
      of screening. In the final study cohort (1784 infants), 15.6% had mild ROP and
      8.5% had severe ROP. Treatment was performed in 4.4% of the infants, none of whom
      had a GA at birth of more than 28 weeks. Nine infants with a GA of more than 28
      weeks at birth developed stage 3 ROP, which regressed spontaneously. The total
      number of examinations was 9286 (964 in infants with a GA of 31 weeks), and the
      mean (range) number of examinations of each infant was 5.2 (1-30). CONCLUSIONS:
      The SWEDROP, a quality register for ROP, has a national coverage (ie,
      participation) of 96%. Data from 2008 to 2009 show that it seems possible to
      reduce the upper limit for screening in Sweden by 1 week, including only infants
      with a GA of 30 weeks + 6 days or less. However, such a change should be combined
      with a strong recommendation to neonatologists to refer also severely ill and
      more "mature" infants.

PMID- 23143443
TI  - Five-decade profile of women in leadership positions at ophthalmic publications.
AB  - OBJECTIVE: To evaluate the balance between the sexes of published ophthalmic
      material at the editorial, reviewer, and author levels. DESIGN: Cross-sectional
      study of 3 journals, American Journal of Ophthalmology, Archives of
      Ophthalmology, and Ophthalmology, for 1969, 1979, 1989, 1999, and 2009. The data
      were compared with ophthalmologist-in-training and physician profile in major
      contributing states from North America and Europe during the same period.
      RESULTS: Of the 3 major ophthalmology journals, none had a female editor-in
      chief. For all journals, the proportion of editorial board members who were women
      increased from 3.3% in 1969 to 18.8% in 2009. For all journals and all years,
      women composed a higher proportion of first authors (29.2% in 2009) compared with
      senior authors (22.9% in 2009), reviewers (18.9% in 2009), or assistant editors
      (12.5% in 2009). There was an abrupt shift toward women after 1989 in first
      authorship in Ophthalmology (1969, 4.6%; 1979, 5.4%; 1989, 12.3%; and 1999,
      20.2%), Archives of Ophthalmology (1969, 6.6%; 1979, 5.1%; 1989, 15.6%; and 1999,
      28.6%), and American Journal of Ophthalmology (1969, 5.6%; 1979, 4.2%; 1989,
      9.2%; and 1999, 23.9%). There was also an abrupt increase in female senior
      authorship for American Journal of Ophthalmology after 1989 (1979, 8.5%; 1989,
      8.1%; and 1999, 18.3%). The increase in female first authorship during the 5
      decades was parallel with the increase in US female physicians. CONCLUSIONS:
      Women ophthalmologists are authoring publications in increasing numbers that
      match their prevalence in the academic and overall workforce. However, all
      editors are men. This discrepancy relates to the relatively younger generation of
      female ophthalmologists or selection bias, a subject that requires further
      investigation.

PMID- 23143442
TI  - BBS1 mutations in a wide spectrum of phenotypes ranging from nonsyndromic
      retinitis pigmentosa to Bardet-Biedl syndrome.
AB  - OBJECTIVE: To investigate the involvement of the Bardet-Biedl syndrome (BBS) gene
      BBS1 p.M390R variant in nonsyndromic autosomal recessive retinitis pigmentosa
      (RP). METHODS: Homozygosity mapping of a patient with isolated RP was followed by
      BBS1 sequence analysis. We performed restriction fragment length polymorphism
      analysis of the p.M390R allele in 2007 patients with isolated RP or autosomal
      recessive RP and in 1824 ethnically matched controls. Patients with 2 BBS1
      variants underwent extensive clinical and ophthalmologic assessment. RESULTS: In
      an RP proband who did not fulfill the clinical criteria for BBS, we identified a
      large homozygous region encompassing the BBS1 gene, which carried the p.M390R
      variant. In addition, this variant was detected homozygously in 10 RP patients
      and 1 control, compound heterozygously in 3 patients, and heterozygously in 5
      patients and 6 controls. The 14 patients with 2 BBS1 variants showed the entire
      clinical spectrum, from nonsyndromic RP to full-blown BBS. In 8 of 14 patients,
      visual acuity was significantly reduced. In patients with electroretinographic
      responses, a rod-cone pattern of photoreceptor degeneration was observed.
      CONCLUSIONS: Variants in BBS1 are significantly associated with nonsyndromic
      autosomal recessive RP and relatively mild forms of BBS. As exemplified in this
      study by the identification of a homozygous p.M390R variant in a control
      individual and in unaffected parents of BBS patients in other studies, cis - or
      trans -acting modifiers may influence the disease phenotype. CLINICAL RELEVANCE:
      It is important to monitor patients with an early diagnosis of mild BBS
      phenotypes for possible life-threatening conditions.

PMID- 23143444
TI  - Scleral fistula closure at the time of glaucoma drainage device tube
      repositioning: a novel technique.
AB  - Repositioning a glaucoma drainage device tube from the anterior chamber to the
      ciliary sulcus or pars plana can be a challenging procedure owing to the
      difficulty in obtaining tight closure of the original limbal fistula. Failure to
      achieve watertight and airtight closure of the fistula can result in substantial
      difficulty in completing other key portions of the surgery and may lead to
      postoperative hypotony and associated complications. A novel technique using a
      Tutoplast scleral plug, polyglactin sutures, and, in certain cases, fibrin tissue
      sealant to close a limbal fistula at the time of glaucoma drainage device tube
      repositioning is described. This technique can be replicated with ease and
      provides a tight seal so that other concurrent surgical procedures can safely be
      completed and postoperative hypotony is avoided.

PMID- 23143445
TI  - Ten years with detached descemet membrane.

PMID- 23143446
TI  - Cataract blindness.

PMID- 23143447
TI  - Carl B. Camras, MD: reflections on his contributions to glaucoma research and
      clinical practice.
AB  - My husband, Carl B. Camras, MD (chairman of the Department of Ophthalmology and
      Visual Sciences, University of Nebraska Medical Center, Omaha), died at age 55
      years in 2009. His dying wish was to be remembered for being the first to
      hypothesize that prostaglandins lower intraocular pressure and had potential as a
      medication to treat glaucoma. I reviewed the research he performed as an
      undergraduate at Yale University (New Haven, Connecticut), as a medical student
      at Columbia University (New York, New York), and on the faculty at Mount Sinai
      School of Medicine (New York, New York), which confirmed his hypothesis and led
      to the development of latanoprost. This article summarizes his contributions to
      glaucoma research, his role in the development of latanoprost, and the error of
      omission that prevented his recognition as its coinventor. Carl is best
      remembered as an ethical scientist, a gifted clinician, and a beloved teacher,
      who inspired the medical community and the next generation of ophthalmologists.

PMID- 23143448
TI  - Real-time polymerase chain reaction for diagnosing acyclovir-resistant herpetic
      keratitis based on changes in viral DNA copy number before and after treatment.

PMID- 23143449
TI  - Live juvenile strobilate tapeworm in the anterior chamber of the human eye.

PMID- 23143450
TI  - Response to ranibizumab following tachyphylaxis to bevacizumab in a patient with
      radiation maculopathy following stereotactic fractionated radiotherapy for optic
      nerve meningioma.

PMID- 23143451
TI  - Bietti crystalline retinopathy: report of retinal crystal deposition in male
      adolescent siblings.

PMID- 23143453
TI  - Successful monitoring and treatment of intraocular dissemination of acanthamoeba.

PMID- 23143454
TI  - Topical linezolid for refractory bilateral Mycobacterium chelonae post-laser
      assisted in situ keratomileusis keratitis.

PMID- 23143455
TI  - Cystic epithelial ingrowth in a case of deep anterior lamellar keratoplasty.

PMID- 23143456
TI  - Conjunctival pigmented epithelioid melanocytoma: a clinicopathological case
      report.

PMID- 23143457
TI  - Projecting the growth of cataract surgery during the next 25 years.

PMID- 23143458
TI  - Novel etiological agent: molecular evidence for trematode-induced anterior
      uveitis in children.

PMID- 23143459
TI  - Eales disease associated with serpiginous choroiditis.

PMID- 23143460
TI  - Detection rate of pathogenic mutations in ABCA4 using direct sequencing: clinical
      and research implications.

PMID- 23143461
TI  - Homozygous deletion in CDH3 and hypotrichosis with juvenile macular dystrophy.

PMID- 23143462
TI  - Bilateral ophthalmic artery occlusions due to probable varicella-zoster virus
      vasculopathy.

PMID- 23143463
TI  - Idiopathic pigmented vitreous cyst.

PMID- 23143464
TI  - Orbital bands in Gomez-Lopez-Hernandez syndrome.

PMID- 23143465
TI  - CD44 expression in intraoral salivary ductal papillomas and oral papillary
      squamous cell carcinoma.
AB  - CD44 is a transmembrane adhesion molecule which has been previously shown to be
      useful in the differentiation of benign papillary lesions from invasive carcinoma
      in several different areas including sinonasal mucosa and breast tissue. CD44
      expression has previously been shown to be lost in invasive carcinoma and
      retained in benign papillary lesions in both of the above locations. In addition,
      studies have evaluated oral mucosal lesions for CD44 expression and found a loss
      with invasive squamous cell carcinoma when compared to normal epithelium,
      hyperplasia, and squamous papillomas, which stained particularly strongly. To the
      best of our knowledge, no study has evaluated CD44 expression when comparing
      salivary ductal papillomas in comparison to oral papillary SCCA. In this study 18
      cases of intraductal papilloma were compared to 19 cases of oral papillary SCCA.
      Within the ductal papilloma group, all cases stained either absent (6%), weakly
      (33%), or moderately (61%) with 76% expressing the stain diffusely and 24%
      focally. In comparison, the papillary squamous cell carcinoma cases expressed the
      CD44 moderately (26%) or strongly (74%) with 100 % showing diffuse staining.
      Thus, the CD44 expression was contrary to expectation based on previous studies,
      which we hypothesize is due to the extremely well differentiated nature of
      papillary SCCA which expressed CD44 staining compatible with levels previously
      reported with oral squamous papillomas than invasive carcinoma.

PMID- 23143466
TI  - Significantly enhanced production of isoprene by ordered coexpression of genes
      dxs, dxr, and idi in Escherichia coli.
AB  - We constructed a biosynthetic pathway of isoprene production in Escherichia coli
      by introducing isoprene synthase (ispS) from Populus alba. 1-deoxy-D-xylulose 5
      phosphate synthase (dxs), 1-deoxy-D-xylulose 5-phosphate reductoisomerase (dxr)
      and isopentenyl diphosphate (IPP) isomerase (idi) were overexpressed to enhance
      the isoprene production. The isoprene production was improved 0.65, 0.16, and
      1.22 fold over the recombinant BL21 (pET-30a-ispS), respectively, and idi was
      found to be a key regulating point for isoprene production. In order to optimize
      the production of isoprene in E. coli, we attempted to construct polycistronic
      operons based on pET-30a with genes dxs, dxr, and idi in various orders. The
      highest isoprene production yield of 2.727 mg g(-1) h(-1) (per dry weight) was
      achieved by E. coli transformed with pET-30a-dxs/dxr/idi. Interestingly, the gene
      order was found to be consistent with that of the metabolic pathway. This
      indicates that order of genes is a significant concern in metabolic engineering
      and a sequential expression pattern can be optimized according to the
      biosynthetic pathway for efficient product synthesis.

PMID- 23143467
TI  - High-level expression and immunogenicity of a porcine circovirus type 2 capsid
      protein through codon optimization in Pichia pastoris.
AB  - The porcine circovirus type 2 (PCV2) capsid protein (Cap) is an important antigen
      for the development of vaccines. To achieve high-level expression of recombinant
      PCV2 Cap in Pichia pastoris, the wild-type Cap (wt-Cap) and optimized Cap (opti
      Cap) gene fragments encoding the same amino acid sequence of PCV2 were amplified
      by PCR using DNA from lymph nodes of postweaning multisystemic wasting syndrome
      suffered pigs and synthesized based on the codon bias of the methylotrophic yeast
      P. pastoris, respectively. The wt-Cap and opti-Cap gene fragments were inserted
      into the site between EcoRI and NotI sites in pPIC9K, which was under the control
      of the alcohol oxidase 1 (AOX1) promoter and alpha-mating factor signal sequence
      from Saccharomyces cerevisiae. The recombinant plasmids, designated as pPIC9K-wt
      Cap and pPIC9K-opti-Cap, were linearized using SacI and transformed into P.
      pastoris GS115 by electroporation. The expressed intracellular soluble opti-Cap
      reached 174 MUg/mL without concentration in a shake flask and kept good
      reactivity to PCV2-specific positive sera, whereas the wt-Cap could not be
      detectable throughout three times electroporation. Strong specific PCV2-Cap
      antibodies were elicited from piglets immunized with vaccine based on opti-Cap.
      To the best of our knowledge, the achieved opti-Cap yield is the highest ever
      reported. Our results demonstrated that codon optimization play an important role
      on the high-level expression of a codon-optimized PCV2-Cap gene in P. pastoris,
      and the vaccine based on opti-Cap may be a potential subunit vaccine candidate.

PMID- 23143468
TI  - Biochemical mutagens affect the preservation of fungi and biodiversity
      estimations.
AB  - Many fungi have significant industrial applications or biosafety concerns and
      maintaining the original characteristics is essential. The preserved fungi have
      to represent the situation in nature for posterity, biodiversity estimations, and
      taxonomic research. However, spontaneous fungal mutations and secondary
      metabolites affecting producing fungi are well known. There is increasing
      interest in the preservation of microbes in Biological Resource Centers (BRC) to
      ensure that the organisms remain viable and stable genetically. It would be
      anathema if they contacted mutagens routinely. However, for the purpose of this
      discussion, there are three potential sources of biochemical mutagens when
      obtaining individual fungi from the environment: (a) mixtures of microorganisms
      are plated routinely onto growth media containing mutagenic antibiotics to
      control overgrowth by contaminants, (b) the microbial mixtures may contain
      microorganisms capable of producing mutagenic secondary metabolites, and (c)
      target fungi for isolation may produce "self" mutagens in pure culture. The
      probability that these compounds could interact with fungi undermines confidence
      in the preservation process and the potential effects of these biochemical
      mutagens are considered for the first time on strains held in BRC in this review.

PMID- 23143469
TI  - Molecular characterization of natural biofilms from household taps with different
      materials: PVC, stainless steel, and cast iron in drinking water distribution
      system.
AB  - Microorganism in drinking water distribution system may colonize in biofilms.
      Bacterial 16S rRNA gene diversities were analyzed in both water and biofilms
      grown on taps with three different materials (polyvinyl chloride (PVC), stainless
      steel, and cast iron) from a local drinking water distribution system. In total,
      five clone libraries (440 sequences) were obtained. The taxonomic composition of
      the microbial communities was found to be dominated by members of Proteobacteria
      (65.9-98.9 %), broadly distributed among the classes Alphaproteobacteria,
      Betaproteobacteria, and Gammaproteobacteria. Other bacterial groups included
      Firmicutes, Acidobacteria, Bacteroidetes, Cyanobacteria, and Deinococcus-Thermus.
      Moreover, a small proportion of unclassified bacteria (3.5-10.6 %) were also
      found. This investigation revealed that the bacterial communities in biofilms
      appeared much more diversified than expected and more care should be taken to the
      taps with high bacterial diversity. Also, regular monitor of outflow water would
      be useful as potentially pathogenic bacteria were detected. In addition,
      microbial richness and diversity in taps ranked in the order as: PVC < stainless
      steel < cast iron. All the results interpreted that PVC would be a potentially
      suitable material for use as tap component in drinking water distribution system.

PMID- 23143470
TI  - Bis(imino)diphenylamido rare-earth metal dialkyl complexes: synthesis, structure,
      and catalytic activity in living ring-opening epsilon-caprolactone polymerization
      and copolymerization with gamma-butyrolactone.
AB  - Bis(imino)diphenylamido rare-earth metal dialkyl complexes [o-(2,6-(i)Pr(2)
      C(6)H(3)-N=C-C(6)H(4))(2)-N]Ln(CH(2)SiMe(3))(2) (1: Ln = Sc; 2: Ln = Lu; 3: Ln =
      Y) have been synthesized in good yields and structurally characterized by
      elemental analysis, NMR spectroscopy, and single-crystal X-ray diffraction
      studies. They serve as highly efficient single-component catalysts both for the
      living ring-opening epsilon-caprolactone polymerization and random
      copolymerization with gamma-butyrolactone, with the activity being dependent on
      the steric hindrance around the metal center, yielding high molecular weight PCLs
      or P(CL-co-BL)s with narrow molecular weight distributions.

PMID- 23143471
TI  - Activated charcoal enhanced the antigen-expression and dendritic cell maturation
      of the vaccine using Listeria-platform.
AB  - BACKGROUND: Listeria monocytogenes (LM) has been used as a vaccine vector based
      upon its ability to induce a strong cell-mediated immune response. LM inactivated
      with gamma-irradiation retains immunogenic properties and is an attractive
      platform for clinical use since it would have improved safety concerns compared
      to live vectors. Activated charcoal has been shown to enhance expression of LM
      proteins such as PrfA. AIM: To investigate the effect of various growth
      conditions supplemented with activated charcoal on recombinant antigen
      expression. METHODS: We prepared gamma-irradiated ovalbumin-expressing LM (LM
      OVA) after growth under various culture conditions. We cultured LM-OVA at various
      temperatures including 25 degrees C, 37 degrees C and 37 degrees C with activated
      charcoal and compared OVA expression by western blot analysis, dendritic cells
      maturation and OVA-specific T cells. RESULTS: The OVA expression was highest in
      gamma-irradiated LM-OVA grown with activated charcoal at 37 degrees C. Compared
      to other growth conditions, gamma-irradiated LM-OVA grown with activated charcoal
      at 37 degrees C induce better DC maturation as well as production of the highest
      number of antigen-specific IFN gamma-secreting T cells. CONCLUSION: The further
      study should be demonstrated the potential to alter growth conditions to enhance
      OVA expression resulting for vaccine vectors, thereby improving their safety and
      efficacy.

PMID- 23143472
TI  - Illness experience: living with arrhythmia and implantable cardioverter
      defibrillator.
AB  - PURPOSE: To describe the illness experience of patients living with arrhythmia
      and implantable cardioverter defibrillator (ICD) and evaluate their experience
      after implantation of the device for gaining insight on care suitable for their
      condition. METHODS: In this qualitative descriptive study, we conducted semi
      structured interviews of 22 outpatients who were visiting certified implant
      facilities. RESULTS: Three categories and seven subcategories emerged from the
      interviews. The ICD patients were (1) Bewilderment Stemming from Arrhythmia and
      ICD Implant, (2) Facing the Reality of Arrhythmia, the ICD and Being Able To
      Continue Life, and (3) Giving Meaning to Living With Arrhythmia and an ICD. The
      ICD patients first experience bewilderment in the form of [Uncertainty about
      One's Own Bodies], [Fear of Arrhythmia Ending My Life], and [Dissatisfaction with
      Unforeseen Results of the ICD]. After discharge from the hospital following ICD
      implantation, they slowly resumed their own lifestyles and [Facing the Reality of
      the ICD and Being Able to Continue Life] and [Confirming and Managing Lifestyle
      Activities]. As they recognized, objectified, and faced changes in their
      lifestyles, they began to practically see themselves as living with arrhythmia
      which required ICD-aided treatment, [Giving Meaning to One's Illness] and
      [Recognition of One's Disease]. And so, they reknit their lives integrated with
      arrhythmia and an ICD. We expressed these results in a schematic model as
      "Learning to Live with Arrhythmia and the ICD". CONCLUSION: These results can be
      used to provide a perspective for assessing care to help patients adapt to life
      after ICD implantation.

PMID- 23143473
TI  - Severe laceration of flexor tendons after locking palmar plate fixation of distal
      radius fracture: a case report.
AB  - We report a case of flexor pollicis longus and flexor digitorum profundus(II)
      laceration as a result of the severe tenosynovitis after volar  locking plate
      fixation of distal radius fracture.

PMID- 23143474
TI  - Subcortically and callosally projecting neurons are distinct neuronal pools in
      the motor cortex of the reeler mouse.
AB  - Subcortically projecting neurons and callosally projecting ones are distinct
      neuronal pools in the cerebral cortex of the rodents. However, cortical  efferent
      neurons are known to project multiple targets transiently by plural collateral
      axons. These plural axons are eliminated during prenatal and postnatal 
      development. In the cerebral cortex of the Reelin-deficient mouse, reeler, which
      is caused by mutation of the reelin gene, cortical efferent neurons are 
      ectopically distributed. However, it is still unknown whether cortical efferent
      neurons in the reeler mouse lose surplus collateral axons or maintain them 
      during developmental periods. If surplus collaterals of malpositioned cortical
      neurons are not eliminated, neurons projecting subcortically may project their 
      axons to the contralateral hemisphere. To test this plausible hypothesis, we made
      double injections of two fluorescent dyes, Fast Blue and Diamidino yellow 
      dihydrochloride into two of three regions, i.e., upper cervical cord, ventral
      lateral thalamic nucleus, and contralateral motor cortex of the normal and 
      reeler mice, to label corticospinal, corticothalamic and callosal commissure
      neurons in the motor cortex, retrogradely. No double labeled neurons were 
      identified in the motor cortex of the normal and reeler mice, although the
      distribution patterns of these cortical efferent neurons were completely 
      different between normal and reeler mice. These findings strongly suggest that
      collateral elimination of cortical efferent neurons during developing  periods
      are not affected in this mutant mouse.

PMID- 23143475
TI  - Class I PI3K-mediated Akt and ERK signals play a critical role in FcepsilonRI
      induced degranulation in mast cells.
AB  - Class IA and IB phosphoinositide 3-kinases (PI3Ks) have been shown to regulate
      mast cell functions such as proliferation, development, survival and
      degranulation, but the functional redundancy between these two PI3K signaling
      pathways in mast cells remains unclear. Here, we have generated mice deficient in
      both class IA regulatory subunit p85alpha and class IB catalytic subunit
      p110gamma, and show that p85alpha(-/-)p110gamma(-/-) mice exhibit a more severe
      defect in mast cell development than single-knockout mice. In addition, the in
      vivo passive cutaneous anaphylaxis reaction of p85alpha(-/-)p110gamma(-/-) mice
      was nearly completely abrogated, whereas single-knockout mice exhibit just
      marginal reduction. Pharmacological inactivation of Akt in wild-type bone marrow
      derived mast cells (BMMCs) led to partial reduction of degranulation, while over
      expression of a constitutively active Akt partially restored the impaired
      degranulation in p85alpha(-/-)p110gamma(-/-) BMMCs. We also found that the
      extracellular signal-regulated kinase (ERK) signaling pathway was activated in a
      PI3K-dependent manner upon FcepsilonRI stimulation and that simultaneous
      inhibition of Akt and ERK resulted in nearly complete blockade of FcepsilonRI
      induced degranulation. Our data provide evidence that Akt and ERK pathways play
      redundant roles in FcepsilonRI-induced degranulation.

PMID- 23143476
TI  - Differential localization and function of antibody-forming cells responsive to
      inactivated or live-attenuated influenza virus vaccines.
AB  - Currently, there are two different types of licensed influenza virus vaccines
      available in the USA, the live attenuated cold-adapted vaccine and the
      inactivated vaccine. Children greater than 2 years of age and adults younger than
      50 years (apart from those suffering from immunodeficiencies or lung disease) may
      choose between the two vaccines. Previous studies have shown that both vaccines
      elicit significant serum antibody responses. However, comprehensive analyses of
      antibody-forming cells (AFCs) in the upper respiratory tract (URT), the critical
      site of pathogen entry, have been lacking. We therefore compared influenza virus
      specific antibody and AFC activities in systemic and mucosal tissues following
      immunizations of cotton rats with inactivated or live-attenuated vaccines,
      including vaccines from the 2009-10 and 2010-11 seasons. Results demonstrated
      that inactivated and live-attenuated vaccines induced virus-specific AFCs, but
      patterns of residence and function were highly disparate. The inactivated vaccine
      elicited AFCs predominantly in the spleen and bone marrow; IgG was the main
      isotype. In contrast, the live attenuated vaccine elicited acute and long
      sustained AFC responses in the diffuse nasal-associated lymphoid tissue (d-NALT)
      and lung, with IgA being the predominant isotype. The appearance of these d-NALT
      URT responses was confirmed by a similar study of the 2009-10 live attenuated
      vaccine in ferrets. Data emphasize that the inactivated and live-attenuated
      vaccines that are each capable of protecting humans from influenza virus disease
      do so by very different modes of immune surveillance.

PMID- 23143477
TI  - Local property characterization of prostate glands using inhomogeneous modeling
      based on tumor volume and location analysis.
AB  - Mechanical property characterization of prostate tumors can enhance the results
      obtained by palpation by providing quantitative and precise diagnostic
      information to surgeons. The multi-focal characteristics of prostate tumors cause
      inhomogeneity and local property variance in the prostate glands, which is one
      reason for inaccurate property characterizations of the tumors. Therefore,
      biomechanical models should include inhomogeneity and local property variance by
      taking into consideration the anatomical information (location and volume) of the
      tumors. We developed six inhomogeneous local prostate models using the finite
      element method, which takes into account the location and volume information of
      prostate tumors. The models were divided into six different sections: lateral
      apex, lateral mid, lateral base, medial apex, medial mid and medial base tumors.
      Information on the location and volume of prostate tumors was obtained using
      pathological analysis. The mechanical properties of prostate tumors were
      estimated using the developed model simulation and the ex vivo indentation
      experiment results from the human resected prostates. The results showed that the
      mean elastic moduli of the normal and tumoral regions were 14.7 and 41.6 kPa,
      respectively. Our models provided more reliable estimates of the elastic moduli
      than the conventionally used Hertz-Sneddon model, and the results from our model
      were more closely correlated with previous studies due to the inclusion of the
      anatomical information via inhomogeneous modeling. These six local models provide
      baseline property criteria for the diagnosis and localization of prostate tumors
      using the optimized elastic moduli of normal prostate tissues.

PMID- 23143478
TI  - In vitro quantification of the performance of model-based mono-planar and bi
      planar fluoroscopy for 3D joint kinematics estimation.
AB  - Model-based mono-planar and bi-planar 3D fluoroscopy methods can quantify intact
      joints kinematics with performance/cost trade-off. The aim of this study was to
      compare the performances of mono- and bi-planar setups to a marker-based gold
      standard, during dynamic phantom knee acquisitions. Absolute pose errors for in
      plane parameters were lower than 0.6 mm or 0.6 degrees  for both mono- and bi
      planar setups. Mono-planar setups resulted critical in quantifying the out-of
      plane translation (error < 6.5 mm), and bi-planar in quantifying the rotation
      along bone longitudinal axis (error < 1.3 degrees ). These errors propagated to
      joint angles and translations differently depending on the alignment of the
      anatomical axes and the fluoroscopic reference frames. Internal-external rotation
      was the least accurate angle both with mono- (error < 4.4 degrees ) and bi-planar
      (error < 1.7 degrees ) setups, due to bone longitudinal symmetries. Results
      highlighted that accuracy for mono-planar in-plane pose parameters is comparable
      to bi-planar, but with halved computational costs, halved segmentation time and
      halved ionizing radiation dose. Bi-planar analysis better compensated for the out
      of-plane uncertainty that is differently propagated to relative kinematics
      depending on the setup. To take its full benefits, the motion task to be
      investigated should be designed to maintain the joint inside the visible volume
      introducing constraints with respect to mono-planar analysis.

PMID- 23143479
TI  - Transgenic cotton: from biotransformation methods to agricultural application.
AB  - Transgenic cotton is among the first transgenic plants commercially adopted
      around the world. Since it was first introduced into the field in the middle of
      1990s, transgenic cotton has been quickly adopted by cotton farmers in many
      developed and developing countries. Transgenic cotton has offered many important
      environmental, social, and economic benefits, including reduced usage of
      pesticides, indirect increase of yield, minimizing environmental pollution, and
      reducing labor and cost. Agrobacterium-mediated genetic transformation method is
      the major method for obtaining transgenic cotton. However, pollen tube pathway
      mediated method is also used, particularly by scientists in China, to breed
      commercial transgenic cotton. Although transgenic cotton plants with disease
      resistance, abiotic stress tolerance, and improved fiber quality have been
      developed in the past decades, insect-resistant and herbicide-tolerant cotton are
      the two dominant transgenic cottons in the transgenic cotton market.

PMID- 23143480
TI  - Genetically modified cotton in India and detection strategies.
AB  - India is one of the largest cotton-growing countries. Cotton is a fiber crop with
      varied applications from making tiny threads to fashionable clothing in the
      textile sector. In the near future, cotton crop will gain popularity as a
      multipurpose crop in India. The commercialization of Bt cotton in 2002 and
      consequently the fast adoption of Bt cotton hybrids by cotton farmers have
      enhanced the cotton production in India. Presently, genetically modified (GM)
      cotton has occupied 21.0 million hectares (mha) that comprise 14% of the global
      area under GM cultivation. In the coming years, improved cotton hybrids, with
      stacked and multiple gene events for improved fiber quality, insect resistance,
      drought tolerance, and herbicide tolerance, would further significantly improve
      the cotton production in India. With the dramatic increase in commercialization
      of GM crops, there is an urgent need to develop cost-effective and robust GM
      detection methods for effective risk assessment and management, post release
      monitoring, and to solve the legal disputes. DNA-based GM diagnostics are most
      robust assays due to their high sensitivity, specificity, and stability of DNA
      molecule.

PMID- 23143481
TI  - Agrobacterium-mediated transformation of cotton.
AB  - There are many methods and techniques that can be used to transfer foreign genes
      into cells. In plant biotechnology, Agrobacterium-mediated transformation is a
      widely used traditional method for inserting foreign genes into plant genome and
      obtaining transgenic plants, particularly for dicot plant species. Agrobacterium
      mediated transformation of cotton involves several important and also critical
      steps, which includes coculture of cotton explants with Agrobacterium, induction
      and selection of stable transgenic cell lines, recovery of plants from transgenic
      cells majorly through somatic embryogenesis, and detection and expression
      analysis of transgenic plants. In this chapter, we describe a detailed step-by
      step protocol for obtaining transgenic cotton plants via Agrobacterium-mediated
      transformation.

PMID- 23143482
TI  - Biolistic transformation of cotton zygotic embryo meristem.
AB  - Biolistic transformation of cotton (Gossypium hirsutum L.) meristems, isolated
      from mature seed, is detailed in this report. A commercially available, helium
      driven biolistic device (Bio-Rad PDS1000/He) was used to bombard gold particles
      coated with a marker gene (uidA or "beta-glucuronidase") into the shoot meristem.
      The penetration of gold particles was dependent on bombardment parameters and it
      was mostly one to two cell layers deep. Stable transformation of epidermal L1
      layer was consistently observed in approximately 5% of the seedlings. Germ line
      transformation was observed in up to 0.71% of bombarded meristems by several
      laboratories. Using this method identification of germ line transformation is
      laborious and time-consuming. However, the protocol described here represents a
      simple and efficient method for generating germ line transformation events. In
      addition, this procedure offers a quick method to evaluate gene constructs in
      cotton tissues (embryos, cotyledons, leaf), especially fibers which originate as
      single cells from the maternal epidermis layer.

PMID- 23143483
TI  - Biolistic transformation of cotton embryogenic cell suspension cultures.
AB  - Genetic transformation of cotton (Gossypium hirsutum L.) is highly dependent on
      the ability to regenerate fertile plants from transgenic cells through somatic
      embryogenesis. Induction of embryogenic cell cultures is genotype dependant.
      However, once embryogenic cell cultures are available, they can be effectively
      used for transformation by Agrobacterium or biolistic bombardment methods. Here I
      describe a detailed procedure to transform cotton embryogenic cell suspension
      cultures by biolistic bombardment. A commercially available, helium-driven
      biolistic device (Bio-Rad PDS1000/He) was used to bombard gold particles coated
      with plasmid DNA (for visual identification of transformed cells and/or
      selection) into embryogenic cells. Stable transformation at a high frequency (up
      to 4% of the transiently expressing cells) is possible. Regeneration of fertile
      transgenic plants from embryogenic cells takes only about 2 months. Another
      advantage of the embryogenic cell suspension cultures is that they are amenable
      for cryopreservation and long-term storage. It is highly preferable to transform
      commercial varieties of choice than obsolete varieties to avoid the genetic drag
      due to backcrossing.

PMID- 23143484
TI  - Cotton transformation via pollen tube pathway.
AB  - Although many gene transfer methods have been employed for successfully obtaining
      transgenic cotton, the major constraint in cotton improvement is the limitation
      of genotype because the majority of transgenic methods require plant regeneration
      from a single transformed cell which is limited by cotton tissue culture.
      Comparing with other plant species, it is difficult to induce plant regeneration
      from cotton; currently, only a limited number of cotton cultivars can be cultured
      for obtaining regenerated plants. Thus, development of a simple and genotype
      independent genetic transformation method is particularly important for cotton
      community. In this chapter, we present a simple, cost-efficient, and genotype
      independent cotton transformation method-pollen tube pathway-mediated
      transformation. This method uses pollen tube pathway to deliver transgene into
      cotton embryo sacs and then insert foreign genes into cotton genome. There are
      three major steps for pollen tube pathway-mediated genetic transformation, which
      include injection of -foreign genes into pollen tube, integration of foreign
      genes into plant genome, and selection of transgenic plants.

PMID- 23143485
TI  - Silicon carbide whisker-mediated transformation of cotton (Gossypium hirsutum
      L.).
AB  - Plant transformation methods are invaluable biotechnological tools to generate
      specific and targeted genetic variation for performance improvement of crop
      plants. Genetic information is created by proper modification during gene cloning
      flanked by proper regulatory sequences and delivered to plants via -different
      plant transformation techniques. Due to being a multipurpose plant, cotton has
      been subjected to different genetic transformation methods to provide the
      breeders with an opportunity to develop alien traits or improve the endogenous
      gene performance that are very difficult or impossible to develop through
      conventional breeding methods. Here we describe the novel physical way of cotton
      transformation with different genes by using embryogeneic calli as continuous
      source of explants.

PMID- 23143486
TI  - Investigating transgene integration and organization in cotton (Gossypium
      hirsutum L.) genome.
AB  - In this chapter, we present detailed experimental procedures for investigating
      integration patterns of transgenes in cotton genome. We use conventional PCR and
      genomic Southern blot hybridization to characterize integration of T-DNA
      components and vector backbone fragments. For multiple copy insertions into the
      same site (complex loci), transgene/transgene junctions (including canonical and
      truncated T-DNA and transgene involved vector backbone sequences) are
      characterized by PCR and sequencing. Inverse PCR (see Note 1) and sequencing is
      used to characterize transgene/cotton genome junctions. Distribution of T-DNA
      insertion in cotton genome is evaluated by analysis of transgene flanking
      sequences. The pre-insertion sites can also be cloned and sequenced (based on the
      flanking sequences) for survey of genomic structure changes brought by transgene
      integration by comparing a pre-insertion site with corresponding transgene/plant
      junctions.

PMID- 23143487
TI  - Estimating the copy number of transgenes in transformed cotton by real-time
      quantitative PCR.
AB  - Transgenic cotton has widely been employed both in commercial cultivation and
      basic research. It is essential to determine which plants contain the transgene
      and in how many copies after transgenic cotton plants are generated. A TaqMan
      quantitative real-time polymerase chain reaction (Tq RT-PCR) method is described
      here to examine transgene copy number in transgenic cotton plants. The estimation
      of two transgene elements, the target gene of green fluorescence protein (GFP)
      and the selective gene of neomycin phosphotransferase II (NPTII), is used as an
      example to detail each step in Tq RT-PCR procedure, including endogenous
      reference gene selection, reference plasmid construction, primer-probe design,
      DNA extraction, real-time PCR, and data analysis. Comparing with traditional
      approach-Southern hybridization -analysis, this method can be used efficiently in
      screening large number of T0 transgenic cotton plants at early stage of
      transformation process as well as identifying transgene homozygotes in a
      segregation population.

PMID- 23143488
TI  - Development of enzyme-linked immunosorbent assay for the detection of Bt protein
      in transgenic cotton.
AB  - Enzyme-linked immunosorbent assays (ELISA) are being used extensively for the
      identification of Bt-protein in Bt transgenic crops. A sandwich ELISA test is the
      most preferable immunoassay for the quantification of Bt-protein in transgenic
      cotton plants. Here, we describe development of sandwich ELISA, employing
      polyclonal rabbit antibody as a capture antibody and HRP-labeled mouse anti-Bt
      protein-antibody as a detector antibody.

PMID- 23143489
TI  - DNA-based diagnostics for genetically modified cotton: decaplex PCR assay to
      differentiate MON531 and MON15985 Bt cotton events.
AB  - The adoption rate and global area under cultivation of genetically modified (GM)
      crops is dramatically increasing in recent past. GM cotton has occupied 25.0
      million hectares (mha) comprising 15.6% of the global area under GM cultivation.
      Bt cotton, expressing delta-endotoxins from Bacillus thuringiensis (Bt), is the
      only commercialized crop in India that is planted on an area of 10.6 mha. With
      the increase in development and commercialization of GM crops, it is necessary to
      develop appropriate qualitative and quantitative methods for detection of
      different GM events. Robust diagnostics for GM detection need to be developed and
      implemented to monitor and detect different events of GM cotton in India. This
      chapter summarizes the methods based on polymerase chain reaction (PCR) being
      employed for detection of different GM events of cotton. We describe a decaplex
      PCR method for identification and differentiation of two major commercialized
      events of Bt cotton, i.e., MON531 and MON15985, in India.

PMID- 23143490
TI  - A simple and rapid method for determining transgenic cotton plants.
AB  - Determining transgenic events is a critical step for obtaining transgenic plants
      as well as the later stage of application. Traditional methods, such as Northern
      blotting and qRT-PCR, for determining transgenic events either require
      radioactively labeled substrates, expensive instruments, or long-time
      commitments, which result in lab and time-consuming as well as expensive costs.
      These methods also require destroying the transgenic events. In this chapter, we
      present a simple and rapid method for determining transgenic cotton plants in
      both laboratory and field conditions. This method is based on the sensitivity of
      transgenic and non-transgenic plants to a specific chemical, such as antibiotics
      or herbicides. This method will facilitate the screening of transgenic events,
      save time, reduce cost, and speed up the application of transgenic technology on
      cotton breeding and production. More important, this is a nondestructive bioassay
      method; the transgenic plants can be transferred into greenhouse or field for the
      later study after the detection process.

PMID- 23143491
TI  - An efficient grafting technique for recovery of transgenic cotton plants.
AB  - Recovery of transgenic cotton plants from tissue culture condition to greenhouse
      condition is a critical step for improving cotton through genetic engineering.
      Traditional methods always cause low survival rate of transplanted plants. In
      1998, we developed an efficient grafting technique for recovery of transgenic
      cotton plants, which significantly increased the survival rate of the
      transplanting regeneration plants. In this chapter, we present a detailed
      protocol for grafting transgenic cotton plants obtaining somatic embryogenesis.

PMID- 23143492
TI  - Inheritance of transgenes in transgenic Bt lines resistance to Helicoerpa
      armigera in upland cotton.
AB  - Six transgenic Bt cotton cultivars (lines) including GKsu12, GK19, MR1, GK5,
      109B, and SGK1 are highly resistant to bollworm from the seedling to boll-setting
      stages in bioassays with detached cotton leaves, though there are differences in
      resistant level and Bt toxin content in these transgenic cottons. Genetics
      analysis reveals that the resistance to Helicoverpa armigera in these six
      transgenic Bt cotton cultivars (lines) are controlled by one pair of dominant
      genes. Allelic tests further demonstrate some populations are in Mendel
      segregation for two nonallelic genes, i.e., the inserted Bt gene in GKsu12 is
      nonallelic to that of SGK1, GK5, 109B, and GK19 and Bt genes in GK19 and SGK1 are
      likely inserted in the same or in close proximity (genetically closely linked),
      while some F(2) produce abnormal segregation patterns, with a segregation of
      resistance to Helicoerpa armigera vary between 15:1 and 3:1, though their Bt
      segregation fit into 15:1 by PCR analysis, suggesting Bt gene silence in these
      populations. Two genes silence may occur in these populations due to the
      homologous sequence by crossing since the silenced individuals accounted for 1/16
      of the F(2) populations for allelic test. To those silenced populations, one of
      their parents all showed high resistance to bollworm.

PMID- 23143493
TI  - Agrobacterium rhizogenes-induced cotton hairy root culture as an alternative tool
      for cotton functional genomics.
AB  - Although well-accepted as the ultimate method for cotton functional genomics,
      Agrobacterium tumefaciens-mediated cotton transformation is not widely used for
      functional analyses of cotton genes and their promoters since regeneration of
      cotton in tissue culture is lengthy and labor intensive. In certain cases, A.
      rhizogenes-induced hairy root culture has been a suitable molecular tool for
      functional analyses of genes and promoters for plants that are difficult to
      regenerate by A. tumefaciens-mediated transformation. Similarly, A. rhizogenes
      induced hairy root cultures are an alternative tool for cotton functional
      genomics. In this chapter, the advantages and disadvantages of using A.
      rhizogenes-induced cotton hairy root culture over A. tumefaciens-mediated cotton
      transformation are discussed. The procedures for transformation, generation,
      selection, and molecular analyses of transgenic cotton hairy roots are introduced
      by describing the functional analysis of a cotton promoter in cotton hairy roots
      generated by A. rhizogenes-mediated transformation.

PMID- 23143494
TI  - Overexpression of miR 156 in cotton via Agrobacterium-mediated transformation.
AB  - microRNAs (miRNAs) are an extensive class of newly identified endogenous small
      regulatory molecules. Many studies show that miRNAs play a critical role in
      almost all biological and metabolic progresses through targeting protein-coding
      genes for mRNA cleavage or translation inhibition. Many miRNAs are also
      identified from cotton using computational and/or experimental approaches,
      including the next generation deep sequencing technology. However, the function
      of the majority of miRNAs are unclear. In this chapter, we describe a detailed
      method for overexpressing miR 156 in cotton using Agrobacterium-mediated genetic
      transformation. This provides an approach to investigate the function and
      regulatory mechanism of miRNAs in cotton.

PMID- 23143495
TI  - Development of transgenic CryIA(c) + GNA cotton plants via pollen tube pathway
      method confers resistance to Helicoverpa armigera and Aphis gossypii Glover.
AB  - Elite cotton cultivar Sumian16 was transformed with p7RPSBK-mGNA-NPTII containing
      Bt (CryIA(c)), Galanthus nivalis agglutinin (GNA) resistance genes and selectable
      marker NptII gene via the pollen tube pathway method and two fertile transgenic
      Bt + GNA plants were obtained in the present study. The integration and
      expression of the Bt and GNA genes were confirmed by molecular biology techniques
      and insect bioassays. Insect bioassays showed that the transformed plants were
      highly toxic to bollworm larvae as well as obviously retarding development of
      aphid populations. PCR analyses and identification of resistance to Kanamycin and
      bollworm showed that the resistance to bollworm for the two transgenic plants was
      dominantly inherited in a Mendelian manner and the two resistance genes and
      selectable marker co-segregated from primary transformed parents to the first
      self-fertilized progeny plants.

PMID- 23143496
TI  - Agrobacterium-mediated transformation of cotton (Gossypium hirsutum) shoot apex
      with a fungal phytase gene improves phosphorus acquisition.
AB  - Cotton is an important world economic crop plant. It is considered that cotton is
      recalcitrant to in vitro proliferation. Somatic embryogenesis and plant
      regeneration has been successful by using hypocotyl, whereas it is highly
      genotype dependent. Here, a genotype-independent cotton regeneration protocol
      from shoot apices is presented. Shoot apices from 3- to 5-day-old seedlings of
      cotton are infected with an Agrobacterium strain, EHA105, carrying the binary
      vector pC-KSA contained phytase gene (phyA) and the marker gene neomycin
      phosphotransferase (NPTII), and directly regenerated as shoots in vitro. Rooted
      shoots can be obtained within 6-8 weeks. Plants that survived by leaf painting
      kanamycin (kan) were -further analyzed by DNA and RNA blottings. The transgenic
      plants with increased the phosphorus (P) acquisition efficiency were obtained
      following the transformation method.

PMID- 23143497
TI  - Genetic transformation of cotton with a harpin-encoding gene hpaXoo confers an
      enhanced defense response against Verticillium dahliae Kleb.
AB  - The soil-borne fungal pathogen Verticillium dahliae Kleb causes Verticillium wilt
      in a wide range of crops including cotton (Gossypium hirsutum). To date, most
      upland cotton varieties are susceptible to V. dahliae and the breeding for cotton
      varieties with the resistance to Verticillium wilt has not been successful.
      Hpa1Xoo is a harpin protein from Xanthomonas oryzae pv. oryzae which induces the
      hypersensitive cell death in plants. When hpa1Xoo was transformed into the
      susceptible cotton line Z35 through Agrobacterium-mediated transformation, the
      transgenic cotton line (T-34) with an improved resistance to Verticillium dahliae
      was obtained. Here, we describe the related research approach, such as Western
      blot, Southern blot, immuno-gold labeling, evaluation of resistance to
      Verticillium dahliae, and how to detect the micro-hypersensitive response and
      oxidative burst elicited by harpin(Xoo) in plant tissue.

PMID- 23143498
TI  - Development of insect-resistant transgenic cotton with chimeric TVip3A
      accumulating in chloroplasts.
AB  - An optimized vip3A gene, designated as vip3A* was chemically synthesized and a
      thi1 gene chloroplast transit peptide coding sequence was attached to its 5' end
      to produce the tvip3A*. vip3A* and tvip3A* genes were transformed into Gossypium
      hirsutum cv. Zhongmiansuo35 mediated by Agrobacterium tumefaciens. Four
      independent transgenic T1 lines with single-copy insertions and unchanged
      phenotypes (CTV1 and CTV2 for tvip3A*, and CV1 and CV2 for vip3A*) were selected
      by Polymerase chain reaction (PCR), Reverse transcription (RT)-PCR, Southern
      blotting, enzyme-linked immunosorbent assay (ELISA), and insect bioassay. As
      expected, the Vip3A* protein of CTV1 and CTV2 were transported to the
      chloroplasts, where they accumulated. Our results suggest that the two tvip3A*
      transgenic lines (CTV1 and CTV2) can be used to develop insect-resistant
      cultivars and could be used as a resource for raising multi-toxins-expressing
      transgenic cotton.

PMID- 23143499
TI  - Determining gene flow in transgenic cotton.
AB  - Gene flow is one of the major concerns associated with the release of transgenic
      plants into the environment. Unrestricted gene flow can results in super weeds,
      reduction in species fitness and genetic diversity, and contamination of
      traditional plants and foods. Thus, it is important and also necessary to
      evaluate the extent of gene flow in the field for transgenic plants already
      released or being considered for a release. Transgenic cotton is among the first
      transgenic crops for commercialization, which are widely cultivated around the
      world. In this chapter, we use transgenic insect resistant cotton and herbicide
      tolerant cotton as two examples to present a field practice method for
      determining transgene flow in cotton. The procedure includes three major
      sections: (1) field design, (2) seed collection, and (3) field and lab bioassay.

PMID- 23143500
TI  - Early re-presentations and the potential role of catheter-directed thrombolysis
      in patients diagnosed with a lower limb deep vein thrombosis: a single-centre
      experience.
AB  - INTRODUCTION: Catheter-directed thrombolysis (CDT) for iliofemoral deep vein
      thrombosis (DVT) restores venous patency, reduces the risk of the post-thrombotic
      syndrome and may reduce longer term treatment costs. This study assessed the
      potential role of CDT in patients with DVT with regard to representation
      following the index event. METHODS: A retrospective review of all patients with a
      positive lower limb DVT scan. Potential suitability of each patient to undergo
      CDT was based on well-recognized inclusion/exclusion criteria. RESULTS: In total,
      1689 patients underwent a DVT-specific lower limb venous duplex. A total of 269
      were found to have a DVT. Fifty-three of these patients met the inclusion
      criteria for CDT (only 2 underwent CDT). Fifty-nine of the 269 patients with an
      index DVT re-presented to our institution with a venous thromboembolism-related
      clinical event. These patients were significantly younger than those who did not
      reattend. A higher proportion of patients who represented were deemed suitable
      for CDT for the index DVT compared with those who did not represent (17/59 versus
      36/210; P = 0.04). CONCLUSION: This pragmatic study highlights the fact that
      significant number of patients return to secondary care with actual/perceived
      complications following initial diagnosis and treatment of a DVT which may have
      been amenable to CDT.

PMID- 23143501
TI  - Comparing hemodynamic effects with three different measurement devices, of two
      methods of external leg compression versus passive leg raising in patients after
      cardiac surgery.
AB  - External leg compression (ELC) may increase cardiac output (CO) in fluid
      responsive patients like passive leg raising (PLR). We compared the hemodynamic
      effects of two methods of ELC and PLR measured by thermodilution (COtd), pressure
      curve analysis ModelflowTM (COmf) and ultra-sound HemoSonicTM (COhs), to evaluate
      the method with the greatest hemodynamic effect and the most accurate less
      invasive method to measure that effect. We compared hemodynamic effects of two
      different ELC methods (circular, A (n = 16), vs. wide, B (n = 13), bandages
      inflated to 30 cm H2O for 15 min) with PLR prior to each ELC method, in 29 post
      operative cardiac surgical patients. Hemodynamic responses were measured with
      COtd, COmf and COhs. PLR A increased COtd from 6.1 +/- 1.7 to 6.3 +/- 1.8 L.min(
      1) (P = 0.016), and increased COhs from 4.9 +/- 1.5 to 5.3 +/- 1.6 L.min(-1) (P =
      0.001), but did not increase COmf. ELC A increased COtd from 6.4 +/- 1.8 to 6.7
      +/- 1.9 L.min(-1) (P = 0.001) and COmf from 6.9 +/- 1.7 to 7.1 +/- 1.8 L.min(-1)
      (P = 0.021), but did not increase COhs. ELC A increased COtd and COmf as in PLR
      A. PLR B increased COtd from 5.4 +/- 1.3 to 5.8 +/- 1.4 L.min(-1) (P < 0.001),
      and COhs from 5.0 +/- 1.0 to 5.4 +/- 1.0 L.min(-1) (P = 0.013), but not COmf. ELC
      B increased COtd from 5.2 +/- 1.2 to 5.4 +/- 1.1 L.min(-1) (P = 0.003), but less
      than during PLR B (P = 0.012), while COmf and COhs did not change. Bland-Altman
      and polar plots showed lower limits of agreement with changes in COtd for COmf
      than for COhs. The circular leg compression increases CO more than bandage
      compression, and is able to increase CO as in PLR. The less invasive ModelflowTM
      can detect these changes reasonably well.

PMID- 23143502
TI  - Communication skills training for dialysis decision-making and end-of-life care
      in nephrology.
AB  - Nephrology fellows often face difficult conversations about dialysis initiation
      or withdrawal but are frequently unprepared for these discussions. Despite
      evidence that communication skills are teachable, few fellowship programs include
      such training. A communication skills workshop for nephrology fellows
      (NephroTalk) focused on delivering bad news and helping patients define care
      goals, including end-of-life preferences. This 4-hour workshop, held in October
      and November 2011, included didactics and practice sessions with standardized
      patients. Participants were nephrology fellows at Duke University and the
      University of Pittsburgh (n=22). Pre- and post-workshop surveys evaluated
      efficacy of the curriculum and measured changes in perceived preparedness on the
      basis on workshop training. Overall, 14% of fellows were white and 50% were male.
      Less than one-third (6 of 22) reported prior palliative care training. Survey
      response rate varied between 86% and 100%. Only 36% (8 of 22) and 38% (8 of 21)
      of respondents had received structured training in discussions for dialysis
      initiation or withdrawal. Respondents (19 of 19) felt that communication skills
      were important to being a "great nephrologist." Mean level of preparedness as
      measured with a five-point Likert scale significantly increased for all skills
      (range, 0.5-1.14; P<0.01), including delivering bad news, expressing empathy, and
      discussing dialysis initiation and withdrawal. All respondents (21 of 21)
      reported they would recommend this training to other fellows. NephroTalk is
      successful for improving preparedness among nephrology fellows for having
      difficult conversations about dialysis decision-making and end-of-life care.

PMID- 23143503
TI  - Renal function and proteinuria after successful immunosuppressive therapies in
      patients with FSGS.
AB  - BACKGROUND AND OBJECTIVES: In the FSGS Clinical Trial, 22 cyclosporine-treated
      and 20 mycophenolate/dexamethasone-treated patients experienced a complete or
      partial remission after 26 weeks, completed 52 weeks of treatment, and were
      studied through 78 weeks. Herein, changes in the urine protein/creatinine ratio
      (UP/C) and estimated GFR (eGFR) throughout the entire study period are defined.
      DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: The FSGS Clinical Trial, which
      was conducted from November 2004 to January 2010, enrolled patients aged 2-40
      years, with eGFR >=40 ml/min per 1.73 m(2) and UP/C >1 mg/mg after >=4 weeks of
      corticosteroid therapy. Both groups received lisinopril or losartan throughout
      the study. UP/C and eGFR were measured at 0, 26, 52, and 78 weeks. RESULTS: The
      median UP/C in the cyclosporine- and mycophenolate/dexamethasone-responsive
      patients fell by 89.8% and 82.7% at 52 weeks; the fall was largely sustained at
      78 weeks (74.7% and 80.3%, respectively). The mean eGFR fell by 19.4% in the
      cyclosporine group and rose by 7.0% in the mycophenolate mofetil/dexamethasone
      group at 52 weeks, but subsequently rose by 16.4% and fell by 2.6%, respectively,
      in the two groups from 52 to 78 weeks. CONCLUSIONS: In this subset of responding
      FSGS patients, the improvement in UP/C after cyclosporine or
      mycophenolate/dexamethasone treatment was largely sustained for 6 months after
      therapy. Reduction in eGFR in the cyclosporine group was improved 6 months after
      cyclosporine was stopped although the levels were lower than baseline in seven
      patients who entered the study with decreased eGFR.

PMID- 23143504
TI  - Urinary angiotensinogen and risk of severe AKI.
AB  - BACKGROUND: Biomarkers of AKI that can predict which patients will develop severe
      renal disease at the time of diagnosis will facilitate timely intervention in
      populations at risk of adverse outcomes. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: Liquid chromatography/tandem mass spectrometry was used to identify
      30 potential prognostic urinary biomarkers of severe AKI in a group of patients
      that developed AKI after cardiac surgery. Angiotensinogen had the best
      discriminative characteristics. Urinary angiotensinogen was subsequently measured
      by ELISA and its prognostic predictive power was verified in 97 patients who
      underwent cardiac surgery between August 1, 2008 and October 6, 2011. RESULTS:
      The urine angiotensinogen/creatinine ratio (uAnCR) predicted worsening of AKI,
      Acute Kidney Injury Network (AKIN) stage 3, need for renal replacement therapy,
      discharge >7 days from sample collection, and composite outcomes of AKIN stage 2
      or 3, AKIN stage 3 or death, and renal replacement therapy or death. The
      prognostic predictive power of uAnCR was improved when only patients classified
      as AKIN stage 1 at the time of urine sample collection (n=79) were used in the
      analysis, among whom it predicted development of stage 3 AKI or death with an
      area under the curve of 0.81. Finally, category free net reclassification
      improvement showed that the addition of uAnCR to a clinical model to predict
      worsening of AKI improved the predictive power. CONCLUSIONS: Elevated uAnCR is
      associated with adverse outcomes in patients with AKI. These data are the first
      to demonstrate the utility of angiotensinogen as a prognostic biomarker of AKI
      after cardiac surgery.

PMID- 23143505
TI  - Clival giant cell tumor presenting with isolated trigeminal nerve involvement.
AB  - Giant cell tumour (GCT) constitutes about 5 % of all skeletal tumors. They rarely
      occur in the skull. When involved, they preferentially involve the sphenoid or
      temporal bones. Skull-base GCTs generally present with multiple cranial nerves
      involvement, most commonly sixth followed by the third cranial nerve. We describe
      a case of clival GCT presenting with an isolated trigeminal nerve involvement in
      a 19-year-old man which was managed by surgery and adjuvant radiation. At 18
      months of follow-up, the patient is clinically asymptomatic. Clival GCT should
      also be considered in the differential diagnosis of any isolated trigeminal nerve
      palsy. Adjuvant radiation has an important role to play in managing this tumour.

PMID- 23143506
TI  - Esteem(r) middle ear device versus conventional hearing aids for rehabilitation
      of bilateral sensorineural hearing loss.
AB  - This retrospective study aimed to evaluate the efficacy of the Esteem((r)) middle
      ear implant in sensorineural hearing loss (SNHL) of different degree as well as
      to compare it with that obtained with conventional hearing aids. Fifteen out of
      30 adults patients who received an Esteem((r)) middle ear device for
      rehabilitation of sensorineural hearing loss met the primary eligibility
      criterion of prior, continuous use of conventional hearing aids. Study population
      included moderate-to-severe SNHL (8 patients) and severe-to-profound SNHL (7
      patients). Audiometric measurements included free-field pure-tone and speech
      audiometry in Esteem((r))-aided, HA-aided, and baseline threshold. For speech
      audiometry, speech reception threshold (SRT) and word recognition score (WRS)
      were assessed. Subjective benefit was evaluated by Client Oriented Scale of
      Improvement (COSI) questionnaire. In all the subjects, SRT and WRS showed
      improvement both with conventional HA and Esteem((r)) in respect to the unaided
      situation. Although not statistically significant, a slight prevalence of the
      Esteem((r)) performances was recorded both audiometrically and as subjective
      satisfaction score. The Esteem((r)) middle ear device demonstrated appreciable
      benefit for rehabilitation of SNHL of different degree, comparable to what can be
      achieved by conventional hearing aids. In addition, this rehabilitative process
      may enable also individuals presenting with severe-to-profound SNHL to achieve
      remarkable functional outcomes.

PMID- 23143507
TI  - Sequence of vestibular deficits in patients with noise-induced hearing loss.
AB  - This study utilized audiometry, and cervical vestibular-evoked myogenic potential
      (cVEMP), ocular VEMP (oVEMP) and caloric tests to investigate the sequence of
      vestibular deficits in patients with noise-induced hearing loss (NIHL). Thirty
      patients with NIHL underwent an inner ear test battery. Another 30 normal
      controls with age- and sex-matched were included for comparison. The abnormal
      percentages of the audiometry, and cVEMP, oVEMP and caloric tests were 100, 70,
      57 and 33 % in NIHL patients, which showed significant differences from 13, 13, 7
      and 3 % in normal controls, respectively. A significantly decreasing trend among
      the four tests, with the sequence of damage from the cochlea, followed by the
      saccule, utricle, and semicircular canals was noted in NIHL patients, but not in
      normal controls. In conclusion, the decreasing order of abnormal percentages in
      the function of the cochlea, saccule, utricle and semicircular canals after
      chronic noise exposure further supports that the pars inferior (cochlea and
      saccule) is more vulnerable to noise exposure than the pars superior (utricle and
      semicircular canals).

PMID- 23143508
TI  - Guidelines for the use of bone metabolic markers in the diagnosis and treatment
      of osteoporosis (2012 edition).
AB  - Recently the clinical application of bone metabolic markers has achieved
      significant progress and the measurements of these indices give us a better
      understanding of the pathogenesis of osteoporosis. Bone metabolic markers were
      adapted to select drug treatment for osteoporosis and to evaluate drug efficacy.
      Therefore, the proper application and assessment of bone metabolic markers in
      clinical practice is very important. To achieve these aims, the committee on the
      guidelines for the use of biochemical markers of bone turnover in osteoporosis
      authorized by the Japan Osteoporosis Society has summarized recent progress in
      bone markers and proposed the proper utilization of bone markers. Although the
      use of bone metabolic markers now has an important role in the daily management
      of osteoporosis, their use in Japan is still insufficient because of insurance
      coverage limitations. Since the Japan Osteoporosis Society first created the 2001
      guidelines, new bone metabolic markers have been introduced into clinical
      practice. The availability of new osteoporosis treatments that promote bone
      formation has changed the clinical application of bone metabolic markers in
      current practice. Therefore, revisions to the current clinical practice are
      needed which led to the proposal to create these new 2012 guidelines.

PMID- 23143509
TI  - Racial/ethnic differences in bone mineral density among older women.
AB  - The epidemiologic information regarding international differences in bone mineral
      density (BMD) in women is currently insufficient. We compared BMD in older women
      across five racial/ethnic groups in four countries. The femoral neck, total hip,
      and lumbar spine BMD were measured in women (aged 65-74 years) from the Study of
      Osteoporotic Fractures (SOF) (5,035 Caucasian women and 256 African American
      women in the US), the Tobago Women's Health Study (116 Afro-Caribbean women), the
      Ms Os Hong Kong Study (794 Hong Kong Chinese women) and the Namwon Study (1,377
      South Korean women). BMD was corrected according to the cross-site calibration
      results for all scanners. When compared with US Caucasian women, the age adjusted
      mean BMD measurements at the hip sites were 21-31 % higher among Tobago Afro
      Caribbean women and 13-23 % higher among African American women. The total hip
      and spine BMD values were 4-5 % lower among Hong Kong Chinese women and 4-7 %
      lower among South Korean women compared to US Caucasians. The femoral neck BMD
      was similar in Hong Kong Chinese women, but higher among South Korean women
      compared to US Caucasians. Current/past estrogen use was a significant
      contributing factor to the difference in BMD between US versus non-US women.
      Differences in body weight partially explained the difference in BMD between
      Asian versus non-Asian women. These findings show substantial racial/ethnic
      differences in BMD even within African or Asian origin individuals, and highlight
      the contributing role of body weight and estrogen use to the geographic and
      racial/ethnic variation in BMD.

PMID- 23143510
TI  - Biomarkers in acute coronary artery disease.
AB  - Death from coronary artery disease is by far the leading cause of death
      worldwide. There is no doubt that a better understanding of atherothrombosis has
      guided development of improved diagnostic facilities as well as revascularization
      technologies in combination with current antithrombotic strategies that have
      altogether impressively reduced acute thromboembolic complications and death from
      cardiovascular causes within the last decades. However, the rate of ischemic
      complications even after optimal revascularization and medical therapy remains
      high. Similarly, morbidity and death associated with chronic ischemic heart
      disease and ischemic cardiomyopathy respectively are constantly rising.
      Therefore, there is still a strong need for effective primary prevention
      strategies, fast and accurate diagnostic procedures as well as for new and smart
      antithrombotic drugs. The review focuses on cardiac troponins, as relevant
      markers of myocardial necrosis, currently used in the diagnostic process of acute
      coronary syndrome. Furthermore, we will discuss the potential role of copeptin, a
      new marker of acute endogenous stress in acute coronary syndrome patients, as
      faster diagnosis might lead to faster treatment as well as improved short- and
      long-term outcome following acute coronary syndrome. Finally, platelets are an
      old, yet rediscovered biomarker for ischemic cardiovascular outcomes that might
      be used to estimate the individual bleeding or thrombotic risk and to tailor
      antiplatelet therapy.

PMID- 23143511
TI  - Neural population partitioning and a concurrent brain-machine interface for
      sequential motor function.
AB  - Although brain-machine interfaces (BMIs) have focused largely on performing
      single-targeted movements, many natural tasks involve planning a complete
      sequence of such movements before execution. For these tasks, a BMI that can
      concurrently decode the full planned sequence before its execution may also
      consider the higher-level goal of the task to reformulate and perform it more
      effectively. Using population-wide modeling, we discovered two distinct
      subpopulations of neurons in the rhesus monkey premotor cortex that allow two
      planned targets of a sequential movement to be simultaneously held in working
      memory without degradation. Such marked stability occurred because each
      subpopulation encoded either only currently held or only newly added target
      information irrespective of the exact sequence. On the basis of these findings,
      we developed a BMI that concurrently decodes a full motor sequence in advance of
      movement and can then accurately execute it as desired.

PMID- 23143512
TI  - Impaired adult myelination in the prefrontal cortex of socially isolated mice.
AB  - Protracted social isolation of adult mice induced behavioral, transcriptional and
      ultrastructural changes in oligodendrocytes of the prefrontal cortex (PFC) and
      impaired adult myelination. Social re-integration was sufficient to normalize
      behavioral and transcriptional changes. Short periods of isolation affected
      chromatin and myelin, but did not induce behavioral changes. Thus, myelinating
      oligodendrocytes in the adult PFC respond to social interaction with chromatin
      changes, suggesting that myelination acts as a form of adult plasticity.

PMID- 23143513
TI  - Optical controlling reveals time-dependent roles for adult-born dentate granule
      cells.
AB  - Accumulating evidence suggests that global depletion of adult hippocampal
      neurogenesis influences its function and that the timing of the depletion affects
      the deficits. However, the behavioral roles of adult-born neurons during their
      establishment of projections to CA3 pyramidal neurons remain largely unknown. We
      used a combination of retroviral and optogenetic approaches to birth date and
      reversibly control a group of adult-born neurons in adult mice. Adult-born
      neurons formed functional synapses on CA3 pyramidal neurons as early as 2 weeks
      after birth, and this projection to the CA3 area became stable by 4 weeks in age.
      Newborn neurons at this age were more plastic than neurons at other stages.
      Notably, we found that reversibly silencing this cohort of ~4-week-old cells
      after training, but not cells of other ages, substantially disrupted retrieval of
      hippocampal memory. Our results identify a restricted time window for adult-born
      neurons essential in hippocampal memory retrieval.

PMID- 23143514
TI  - Subcellular connectivity underlies pathway-specific signaling in the nucleus
      accumbens.
AB  - We found that medium spiny neurons (MSNs) in both the direct and indirect
      pathways of the mouse nucleus accumbens (NAc) receive inputs from the cortex,
      thalamus and hippocampus. However, hippocampal inputs were much weaker onto
      indirect MSNs, where they contacted small spines located in the distal dendrites.
      This selective targeting means that these inputs must be gated by subthreshold
      depolarization to trigger action potentials and influence NAc output.

PMID- 23143515
TI  - GKAP orchestrates activity-dependent postsynaptic protein remodeling and
      homeostatic scaling.
AB  - How does chronic activity modulation lead to global remodeling of proteins at
      synapses and synaptic scaling? Here we report that guanylate kinase-associated
      protein (GKAP; also known as SAPAP), a scaffolding molecule linking NMDA receptor
      PSD-95 to Shank-Homer complexes, acts in these processes. Overexcitation removes
      GKAP from synapses via the ubiquitin-proteasome system, whereas inactivity
      induces synaptic accumulation of GKAP in rat hippocampal neurons. Bidirectional
      changes in synaptic GKAP amounts are controlled by specific CaMKII isoforms
      coupled to different Ca(2+) channels. CaMKIIalpha activated by the NMDA receptor
      phosphorylates GKAP Ser54 to induce polyubiquitination of GKAP. In contrast,
      CaMKIIbeta activation via L-type voltage-dependent calcium channels promotes GKAP
      recruitment by phosphorylating GKAP Ser340 and Ser384, which uncouples GKAP from
      myosin Va motor complex. Overexpressing GKAP turnover mutants not only hampers
      activity-dependent remodeling of PSD-95 and Shank but also blocks bidirectional
      synaptic scaling. Therefore, activity-dependent turnover of PSD proteins
      orchestrated by GKAP is critical for homeostatic plasticity.

PMID- 23143516
TI  - Orthogonal micro-organization of orientation and spatial frequency in primate
      primary visual cortex.
AB  - Orientation and spatial frequency tuning are highly salient properties of neurons
      in primary visual cortex (V1). The combined organization of these particular
      tuning properties in the cortical space will strongly shape the V1 population
      response to different visual inputs, yet it is poorly understood. In this study,
      we used two-photon imaging in macaque monkey V1 to demonstrate the three
      dimensional cell-by-cell layout of both spatial frequency and orientation tuning.
      We first found that spatial frequency tuning was organized into highly structured
      maps that remained consistent across the depth of layer II/III, similarly to
      orientation tuning. Next, we found that orientation and spatial frequency maps
      were intimately related at the fine spatial scale observed with two-photon
      imaging. Not only did the map gradients tend notably toward orthogonality, but
      they also co-varied negatively from cell to cell at the spatial scale of cortical
      columns.

PMID- 23143517
TI  - Developmental pathways to amygdala-prefrontal function and internalizing symptoms
      in adolescence.
AB  - Early life stress (ELS) and function of the hypothalamic-pituitary-adrenal axis
      predict later psychopathology. Animal studies and cross-sectional human studies
      suggest that this process might operate through amygdala-ventromedial prefrontal
      cortex (vmPFC) circuitry implicated in the regulation of emotion. Here we
      prospectively investigated the roles of ELS and childhood basal cortisol amounts
      in the development of adolescent resting-state functional connectivity (rs-FC),
      assessed by functional connectivity magnetic resonance imaging (fcMRI), in the
      amygdala-PFC circuit. In females only, greater ELS predicted increased childhood
      cortisol levels, which predicted decreased amygdala-vmPFC rs-FC 14 years later.
      For females, adolescent amygdala-vmPFC functional connectivity was inversely
      correlated with concurrent anxiety symptoms but positively associated with
      depressive symptoms, suggesting differing pathways from childhood cortisol levels
      function through adolescent amygdala-vmPFC functional connectivity to anxiety and
      depression. These data highlight that, for females, the effects of ELS and early
      HPA-axis function may be detected much later in the intrinsic processing of
      emotion-related brain circuits.

PMID- 23143518
TI  - Closed-loop optogenetic control of thalamus as a tool for interrupting seizures
      after cortical injury.
AB  - Cerebrocortical injuries such as stroke are a major source of disability.
      Maladaptive consequences can result from post-injury local reorganization of
      cortical circuits. For example, epilepsy is a common sequela of cortical stroke,
      but the mechanisms responsible for seizures following cortical injuries remain
      unknown. In addition to local reorganization, long-range, extra-cortical
      connections might be critical for seizure maintenance. In rats, we found that the
      thalamus, a structure that is remote from, but connected to, the injured cortex,
      was required to maintain cortical seizures. Thalamocortical neurons connected to
      the injured epileptic cortex underwent changes in HCN channel expression and
      became hyperexcitable. Targeting these neurons with a closed-loop optogenetic
      strategy revealed that reducing their activity in real-time was sufficient to
      immediately interrupt electrographic and behavioral seizures. This approach is of
      therapeutic interest for intractable epilepsy, as it spares cortical function
      between seizures, in contrast with existing treatments, such as surgical
      lesioning or drugs.

PMID- 23143519
TI  - PDF-1 neuropeptide signaling modulates a neural circuit for mate-searching
      behavior in C. elegans.
AB  - Appetitive behaviors require complex decision making that involves the
      integration of environmental stimuli and physiological needs. C. elegans mate
      searching is a male-specific exploratory behavior regulated by two competing
      needs: food and reproductive appetite. We found that the pigment dispersing
      factor receptor (PDFR-1) modulates the circuit that encodes the male reproductive
      drive that promotes male exploration following mate deprivation. PDFR-1 and its
      ligand, PDF-1, stimulated mate searching in the male, but not in the
      hermaphrodite. pdf-1 was required in the gender-shared interneuron AIM, and the
      receptor acted in internal and external environment-sensing neurons of the shared
      nervous system (URY, PQR and PHA) to produce mate-searching behavior. Thus, the
      pdf-1 and pdfr-1 pathway functions in non-sex-specific neurons to produce a male
      specific, goal-oriented exploratory behavior. Our results indicate that secretin
      neuropeptidergic signaling is involved in regulating motivational internal
      states.

PMID- 23143520
TI  - A chemical genetic approach reveals distinct EphB signaling mechanisms during
      brain development.
AB  - EphB receptor tyrosine kinases control multiple steps in nervous system
      development. However, it remains unclear whether EphBs regulate these different
      developmental processes directly or indirectly. In addition, given that EphBs
      signal through multiple mechanisms, it has been challenging to define which
      signaling functions of EphBs regulate particular developmental events. To address
      these issues, we engineered triple knock-in mice in which the kinase activity of
      three neuronally expressed EphBs can be rapidly, reversibly and specifically
      blocked. We found that the tyrosine kinase activity of EphBs was required for
      axon guidance in vivo. In contrast, EphB-mediated synaptogenesis occurred
      normally when the kinase activity of EphBs was inhibited, suggesting that EphBs
      mediate synapse development by an EphB tyrosine kinase-independent mechanism.
      Taken together, our data indicate that EphBs control axon guidance and
      synaptogenesis by distinct mechanisms and provide a new mouse model for
      dissecting EphB function in development and disease.

PMID- 23143521
TI  - Diverse types of genetic variation converge on functional gene networks involved
      in schizophrenia.
AB  - Despite the successful identification of several relevant genomic loci, the
      underlying molecular mechanisms of schizophrenia remain largely unclear. We
      developed a computational approach (NETBAG+) that allows an integrated analysis
      of diverse disease-related genetic data using a unified statistical framework.
      The application of this approach to schizophrenia-associated genetic variations,
      obtained using unbiased whole-genome methods, allowed us to identify several
      cohesive gene networks related to axon guidance, neuronal cell mobility, synaptic
      function and chromosomal remodeling. The genes forming the networks are highly
      expressed in the brain, with higher brain expression during prenatal development.
      The identified networks are functionally related to genes previously implicated
      in schizophrenia, autism and intellectual disability. A comparative analysis of
      copy number variants associated with autism and schizophrenia suggests that
      although the molecular networks implicated in these distinct disorders may be
      related, the mutations associated with each disease are likely to lead, at least
      on average, to different functional consequences.

PMID- 23143522
TI  - Neuroligin-1-dependent competition regulates cortical synaptogenesis and synapse
      number.
AB  - Members of the neuroligin family of cell-adhesion proteins are found at
      excitatory and inhibitory synapses and are mutated in some familial forms of
      autism spectrum disorders. Although they display synaptogenic properties in
      heterologous systems, the function of neuroligins in vivo in the regulation of
      synapse formation and synapse number has been difficult to establish. We found
      that neuroligin-1 (NL1), which is located at excitatory postsynaptic densities,
      regulates activity-dependent synaptogenesis and mature synapse number on cortical
      layer 2/3 pyramidal neurons in vivo. However, synapse number was not sensitive to
      absolute NL1 levels but instead depended on transcellular differences in the
      relative amounts of NL1. These effects were independent of the cell-autonomous
      regulation of NMDA-type glutamate receptors by absolute levels of NL1. Our data
      indicate that transcellular competitive processes govern synapse formation and
      number in developing cortex and that NL1 has a central function in these
      processes.

PMID- 23143523
TI  - Veteran subjects willingness to participate in schizophrenia clinical trials.
AB  - Predictive characteristics of subjects agreeing to be randomized into clinical
      trials for the treatment of schizophrenia and schizoaffective disorder have been
      little studied. In this study, we used data from the recruitment phase of a
      randomized trial that compared long acting injectable (LAI) risperidone to oral
      antipsychotic medications. Basic socio-demographic and clinical data were
      gathered from eligible patients and clinicians at the time of screening for trial
      entry. Bivariate comparisons and multivariate logistic regression were used to
      compare those who agreed to participate and those who refused. Altogether 446
      veterans were eligible on preliminary screening, of these 382 (86 %) agreed to
      participate and 64 (14 %) declined. Eligible patients who agreed to be randomized
      were more willing to change medications without regard to their level of
      satisfaction with their current medication. Subjects reported as currently taking
      LAI medication and taking risperidone, in particular, were more likely to agree
      to participate. Factors that did not significantly predict participation included
      age, years on current medication, reported medication compliance, race, and
      gender. Veterans with schizophrenia or schizoaffective disorder who were actually
      more satisfied with their current medications and who were currently taking the
      experimental agent were more likely to agree to participate in this randomized
      clinical trial in contrast to expectations that individuals who are unsatisfied
      with their current treatment would be more likely to enroll in such studies.

PMID- 23143524
TI  - A standardised protocol for the validation of banking methodologies for arterial
      allografts.
AB  - The objective of this study was to design and test a protocol for the validation
      of banking methodologies for arterial allografts. A series of in vitro
      biomechanical and biological assessments were derived, and applied to paired
      fresh and banked femoral arteries. The ultimate tensile stress and strain, suture
      pullout stress and strain, expansion/rupture under hydrostatic pressure,
      histological structure and biocompatibility properties of disinfected and
      cryopreserved femoral arteries were compared to those of fresh controls. No
      significant differences were detected in any of the test criteria. This
      validation protocol provides an effective means of testing and validating banking
      protocols for arterial allografts.

PMID- 23143525
TI  - Precise determination of time to reach viral load set point after acute HIV-1
      infection.
AB  - OBJECTIVE: The HIV viral load set point has long been used as a prognostic marker
      of disease progression and more recently as an end-point parameter in HIV vaccine
      clinical trials. The definition of set point, however, is variable. Moreover, the
      earliest time at which the set point is reached after the onset of infection has
      never been clearly defined. METHODS: In this study, we obtained sequential plasma
      viral load data from 60 acutely HIV-infected Chinese patients among a cohort of
      men who have sex with men, mathematically determined viral load set point levels,
      and estimated time to attain set point after infection. We also compared the
      results derived from our models and that obtained from an empirical method.
      RESULTS: With novel uncomplicated mathematic model, we discovered that set points
      may vary from 21 to 119 days dependent on the patients' initial viral load
      trajectory. The viral load set points were 4.28 +/- 0.86 and 4.25 +/- 0.87 log10
      copies per milliliter (P = 0.08), respectively, as determined by our model and an
      empirical method, suggesting an excellent agreement between the old and new
      methods. CONCLUSIONS: We provide a novel method to estimate viral load set point
      at the very early stage of HIV infection. Application of this model can
      accurately and reliably determine the set point, thus providing a new tool for
      physicians to better monitor early intervention strategies in acutely infected
      patients and scientists to rationally design preventative vaccine studies.

PMID- 23143527
TI  - Novel metal(II) coordination polymers based on N,N'-bis-(4-pyridyl)phthalamide as
      supercapacitor electrode materials in an aqueous electrolyte.
AB  - Based on the redox-active L (N,N'-bis-(4-pyridyl)phthalamide) ligand, two porous
      MOFs formulated as Zn(6)(BPC)(6)(L)(3).9DMF (H(2)BPC = 4,4'-biphenyldicarboxylic
      acid) (1) and Cd(2)(TDC)(2)(L)(2).4H(2)O (H(2)TDC = 2,5-thiophenedicarboxylic
      acid) (2) were synthesized and structurally characterized by single-crystal X-ray
      diffractions. Complex 1 features a uninodal 5-connected 3-fold interpenetrated 3D
      framework with {4(6).6(4)}-bnn hexagonal BN topology. Complex 2 displays a
      uninodal 6-connected 2-fold interpenetrated 3D framework with {4(12).6(3)}-pcu
      topology. When complexes 1 and 2 are used as supercapacitor electrode materials,
      they can provide a large voltage window as high as 2.6 V in an aqueous
      electrolyte, and their specific capacitances are much more than the value for the
      bare carbon glassy electrode. It is observed that the more the current density,
      the less the specific capacitance for the two kinds of supercapacitor electrode
      materials. The two complexes show different thermal stabilities, UV absorption
      and photoluminescence properties.

PMID- 23143526
TI  - Risk factors for falls in HIV-infected persons.
AB  - BACKGROUND: The incidence of and risk factors for falls in HIV-1-infected persons
      are unknown. METHODS: Fall history during the prior 12 months, medical diagnoses,
      and functional assessments were collected on HIV-infected persons 45-65 years of
      age receiving effective antiretroviral therapy. Fall risk was evaluated using
      univariate and multivariate regression analyses. RESULTS: Of 359 subjects, 250
      persons (70%) reported no falls, 109 (30%) had >=1 fall; and 66 (18%) were
      recurrent fallers. Females, whites, and smokers were more likely to be recurrent
      fallers (P <= 0.05). HIV-related characteristics including current and nadir CD4
      T-cell count, estimated HIV duration, and Veterans Aging Cohort Study Index
      scores were not predictors of falls (all P >= 0.09); didanosine recipients were
      more likely to be recurrent fallers (P = 0.04). The odds of falling increased 1.7
      for each comorbidity and 1.4 for each medication (P < 0.001) and were higher in
      persons with cardiovascular disease, hypertension, dementia, neuropathy,
      arthritis, chronic pain, psychiatric disease, frailty, or disability [all odds
      ratio (OR) >= 1.8; P <= 0.05]. Beta-blockers, antidepressants, antipsychotics,
      sedatives, and opiates were independently associated with falling (all OR >= 2.7;
      P <= 0.01). Female gender, diabetes, antidepressants, sedatives, opiates,
      didanosine, exhaustion, weight loss, and difficulty with balance were the most
      significant predictors of falls in logistic regression (all OR >= 2.5; P <=
      0.05). CONCLUSIONS: Middle-aged HIV-infected adults have high fall risk. Multiple
      comorbidities, medications, and functional impairment were predictive of falls,
      but surrogate markers of HIV infection or an HIV-specific multimorbidity index
      were not. Fall risk should be assessed routinely as part of the care of HIV
      infected persons.

PMID- 23143528
TI  - Cartographers in an uncharted terrain--the importance of going the extra mile.

PMID- 23143529
TI  - How reliable is the Internet for caregivers on their decision to vaccinate their
      child against influenza? Results from googling in two languages.
AB  - We have chosen Google, which is the most widely used search engine, to simulate a
      parent's experience in trying to find an answer on whether to have her/his child
      vaccinated against influenza. In doing this, we aimed to find out the chances
      that a parent with usual Internet searching tendencies may encounter right,
      wrong, and irrelevant answers in her/his search in the world wide web. We
      searched the Internet for an answer to the question "Should I make my child
      vaccinated against influenza?" by using the keywords "influenza", "vaccine", and
      "children" in two languages (English and Turkish). The "correct" answer was at
      least one clear statement meaning that annual influenza vaccination is
      recommended for all children (aged 6 months-18 years). Thirty-two of the 112
      websites and 45 of the 103 websites had the correct answer, whereas 24 and 46
      websites contained incorrect information in English and Turkish searches,
      respectively. Only non-relevant information was found in 56 English and 12
      Turkish websites. When the first page of search results were taken into account,
      correctness and incorrectness were observed in six and four English and four and
      six in Turkish websites, respectively. Our findings call for the urgent need to
      check public-oriented healthcare information on the Internet for accuracy,
      completeness, and consistency. We have arrived at a conclusion that the
      information on the Internet cannot and should not be a substitute for routine
      care by primary care physicians.

PMID- 23143530
TI  - Target-oriented discovery of a new esterase-producing strain Enterobacter sp.
      ECU1107 for whole cell-catalyzed production of (2S,3R)-3-phenylglycidate as a
      chiral synthon of Taxol.
AB  - A new strain, Enterobacter sp. ECU1107, was identified among over 200 soil
      isolates using a two-step screening strategy for the enantioselective synthesis
      of (2S,3R)-3-phenylglycidate methyl ester (PGM), a key intermediate for
      production of a potent anticancer drug Taxol(r). An organic-aqueous biphasic
      system was employed to reduce spontaneous hydrolysis of the substrate PGM and
      isooctane was found to be the most suitable organic solvent. The temperature and
      pH optima of the whole cell-mediated bioreaction were 40  degrees C and 6.0,
      respectively. Under these reaction conditions, the enantiomeric excess (ee(s)) of
      (2S,3R)-PGM recovered was greater than 99 % at approximately 50 % conversion. The
      total substrate loading in batch reaction could reach 600 mM. By using whole
      cells of Enterobacter sp. ECU1107, (2S,3R)-PGM was successfully prepared in
      decagram scale in a 1.0-l mechanically stirred reactor, affording the chiral
      epoxy ester in >99 % ee s and 43.5 % molar yield based on the initial load of
      racemic substrate.

PMID- 23143531
TI  - Influence of mass transfer on stable isotope fractionation.
AB  - Biodegradation of contaminants is a common remediation strategy for subsurface
      environments. To monitor the success of such remediation means a quantitative
      assessment of biodegradation at the field scale is required. Nevertheless, the
      reliable quantification of the in situ biodegradation process it is still a major
      challenge. Compound-specific stable isotope analysis has become an established
      method for the qualitative analysis of biodegradation in the field and this
      method is also proposed for a quantitative analysis. However, to use stable
      isotope data to obtain quantitative information on in situ biodegradation
      requires among others knowledge on the influence of mass transfer processes on
      the observed stable isotope fractionation. This paper reviews recent findings on
      the influence of mass transfer processes on stable isotope fractionation and on
      the quantitative interpretation of isotope data. Focus will be given on small
      scale mass transfer processes controlling the bioavailability of contaminants.
      Such bioavailability limitations are known to affect the biodegradation rate and
      have recently been shown to affect stable isotope fractionation, too. Theoretical
      as well as experimental studies addressing the link between bioavailability and
      stable isotope fractionation are reviewed and the implications for assessing
      biodegradation in the field are discussed.

PMID- 23143532
TI  - Partial nitrifying granule stimulated by struvite carrier in treating
      pharmaceutical wastewater.
AB  - Aerobic granule was successfully cultivated in SBR (sequencing batch reactor) by
      struvite carrier (magnesium ammonium phosphate, MgNH4PO4), which can increase
      polysaccharides to 42.2 mg/gMLVSS (mixed liquor volatile suspended solid) versus
      only 28.4 mg/gMLVSS of the sludge without it. Meanwhile, it was found that
      struvite play a positive role in initial granulation and bacterial group
      distribution in treating pharmaceutical wastewater, involving effect of solid
      surface and special contents of struvite. The results of fluorescence in situ
      hybridization technique indicate that ammonia-oxidizing bacteria can dominate
      over nitrite-oxidizing bacteria in mature granules. COD removal efficiency of 90
      % and NO2 (-)-N:(NO2 (-)-N + NO3 (-)-N) accumulation efficiency of 89 % were
      achieved in stable state. Emphasis is placed on that struvite addition can be
      applied as a new-type carrier to promote formation of partial nitrification
      granular sludge. 

PMID- 23143533
TI  - Co-digestion of manure and whey for in situ biogas upgrading by the addition of
      H(2): process performance and microbial insights.
AB  - In situ biogas upgrading was conducted by introducing H(2) directly to the
      anaerobic reactor. As H(2) addition is associated with consumption of the CO(2)
      in the biogas reactor, pH increased to higher than 8.0 when manure alone was used
      as substrate. By co-digestion of manure with acidic whey, the pH in the anaerobic
      reactor with the addition of hydrogen could be maintained below 8.0, which did
      not have inhibition to the anaerobic process. The H(2) distribution systems
      (diffusers with different pore sizes) and liquid mixing intensities were
      demonstrated to affect the gas-liquid mass transfer of H(2) and the biogas
      composition. The best biogas composition (75:6.6:18.4) was obtained at stirring
      speed 150 rpm and using ceramic diffuser, while the biogas in the control reactor
      consisted of CH(4) and CO(2) at a ratio of 55:45. The consumed hydrogen was
      almost completely converted to CH(4), and there was no significant accumulation
      of VFA in the effluent. The study showed that addition of hydrogen had positive
      effect on the methanogenesis, but had no obvious effect on the acetogenesis. Both
      hydrogenotrophic methanogenic activity and the concentration of coenzyme F(420)
      involved in methanogenesis were increased. The archaeal community was also
      altered with the addition of hydrogen, and a Methanothermobacter
      thermautotrophicus related band appeared in a denaturing gradient gel
      electrophoresis gel from the sample of the reactor with hydrogen addition. Though
      the addition of hydrogen increased the dissolved hydrogen concentration, the
      degradation of propionate was still thermodynamically feasible at the reactor
      conditions.

PMID- 23143534
TI  - In vivo random mutagenesis of streptomycetes using mariner-based transposon
      Himar1.
AB  - We report here the in vivo expression of the synthetic transposase gene himar1(a)
      in Streptomyces coelicolor M145 and Streptomyces albus. Using the synthetic
      himar1(a) gene adapted for Streptomyces codon usage, we showed random insertion
      of the transposon into the streptomycetes genome. The insertion frequency for the
      Himar1-derived minitransposons is nearly 100 % of transformed Streptomyces cells,
      and insertions are stably inherited in the absence of an antibiotic selection.
      The minitransposons contain different antibiotic resistance selection markers
      (apramycin, hygromycin, and spectinomycin), site-specific recombinase target
      sites (rox and/or loxP), I-SceI meganuclease target sites, and an R6Kgamma origin
      of replication for transposon rescue. We identified transposon insertion loci by
      random sequencing of more than 100 rescue plasmids. The majority of insertions
      were mapped to putative open-reading frames on the S. coelicolor M145 and S.
      albus chromosomes. These insertions included several new regulatory genes
      affecting S. coelicolor M145 growth and actinorhodin biosynthesis.

PMID- 23143537
TI  - Role of F-18 FDG PET/CT in assessing bone marrow involvement in pediatric
      Hodgkin's lymphoma.
AB  - OBJECTIVES: The aim of the current study was to assess the utility of F-18-fluoro
      2-deoxy-D-glucose (F-18 FDG) positron emission tomography/computed tomography
      (PET/CT) in assessing bone marrow involvement (BMI) compared to bone marrow
      biopsy (BMB) in initial staging of Hodgkin's lymphoma (HL) in pediatric patients.
      METHODS: Data of 38 pediatric patients (mean age 9.8 years, range 3-18 years)
      with HL were analyzed for the involvement of bone marrow. All patients underwent
      non-contrast F-18 FDG PET/CT study. BMB was done in 31 patients from the
      bilateral iliac crests. Scans were interpreted by two nuclear medicine physicians
      blinded to the details of BMB. RESULTS: Of the 31 patients who underwent BMB, 5
      patients had lymphomatous involvement on BMB. PET/CT was positive in four of
      these five patients. In 26 patients negative on BMB, PET was negative in 23
      patients and positive in 3 patients for BMI. The sensitivity and negative
      predictive value of F-18 FDG PET/CT was 87.5 and 96%, respectively, for BMI.
      CONCLUSIONS: F-18 FDG PET/CT can predict BMB results with high accuracy. F-18 FDG
      PET/CT may be used at initial staging of pediatric Hodgkin's lymphoma as it
      uncovers unsuspected BMI and BMB may be omitted in patients with PET-positive
      BMI.

PMID- 23143535
TI  - New strategies for drug discovery: activation of silent or weakly expressed
      microbial gene clusters.
AB  - Genome sequencing of Streptomyces, myxobacteria, and fungi showed that although
      each strain contains genes that encode the enzymes to synthesize a plethora of
      potential secondary metabolites, only a fraction are expressed during
      fermentation. Interest has therefore grown in the activation of these cryptic
      pathways. We review current progress on this topic, describing concepts for
      activating silent genes, utilization of "natural" mutant-type RNA polymerases and
      rare earth elements, and the applicability of ribosome engineering to
      myxobacteria and fungi, the microbial groups known as excellent searching
      sources, as well as actinomycetes, for secondary metabolites.

PMID- 23143539
TI  - Surgical treatment of chronic thromboembolic pulmonary hypertension.
AB  - It is likely that chronic thromboembolic pulmonary hypertension (CTEPH) is more
      prevalent than currently recognised. Imaging studies are fundamental to decision
      making with respect to operability. All patients with suspected CTEPH should be
      referred to an experienced surgical centre. Currently, there is no risk scoring
      stratification system to guide operability assessment and it is predominantly
      based on surgical experience. The aim of pulmonary endarterectomy (PEA) is the
      removal of obstructive material to immediately reduce pulmonary vascular
      resistance. PEA affords the best chance of cure, but is difficult to perfect.
      Recognition and clearance of distal segmental and subsegmental disease is the
      main problem. The basic surgical techniques include: median sternotomy incision,
      cardiopulmonary bypass, arteriotomy incisions within pericardium, and a true
      endarterectomy with meticulous full distal dissection. Deep hypothermic
      circulatory arrest is recommended as the best means of reducing blood flow in the
      pulmonary artery to allow a clear field for dissection. In the recent PEACOG (PEA
      and COGnition) trial there was no evidence of cognitive impairment post-PEA.
      Reperfusion pulmonary oedema and residual pulmonary hypertension are unique post
      operative complications post-PEA and are associated with increased mortality.
      However, in-hospital mortality is now <5% in experienced centres.

PMID- 23143538
TI  - Kinsenoside prevents ovariectomy-induced bone loss and suppresses
      osteoclastogenesis by regulating classical NF-kappaB pathways.
AB  - Kinsenoside is able to improve bone turnover rate in ovariectomized (OVX) mice.
      In vitro analysis shows that kinsenoside antagonizes osteoclast development and
      bone resorption. INTRODUCTION: Kinsenoside, the main active compound of the
      traditional Taiwanese herb Anoectochilus formosanus, has an antiinflammatory
      effect. This study investigates whether kinsenoside inhibits osteoporosis and
      osteoclastogenesis. METHODS: OVX mice were used to examine the antiosteoporotic
      activity of kinsenoside. The trabecular bone microarchitecture was assessed by
      microcomputed tomography. In vitro experiments were performed to determine the
      mechanisms of the antiosteoporotic effects of kinsenoside. RESULTS: Microcomputed
      tomography scanning showed that kinsenoside suppresses bone loss in OVX mice.
      Kinsenoside decreases plasma CTx concentration. Reverse transcription polymerase
      chain reaction (RT-PCR) analysis also showed that kinsenoside reduces the femoral
      mRNA expression of tartrate-resistant acid phosphatase (TRAP) and matrix
      metalloproteinase-9 (MMP-9). Kinsenoside inhibits osteoclast formation in bone
      marrow cells (BMs) and RAW 264.7 cells. Western blot was used to analyze
      osteoclast-associated signaling pathways in RAW 264.7 cells. Results show that
      kinsenoside does not inhibit IKK phosphorylation but suppresses the
      phosphorylation of IkappaBalpha and p65. Kinsenoside significantly inhibits the
      RANKL induction of IKK activity. Kinsenoside inhibits the RANKL-triggered nuclear
      translocations of NF-kappaB and nuclear factor of activated T cells c1 (NFATc1).
      RT-PCR was used to analyze osteoclast precursor fusion and resorption-associated
      gene expression in BMs. Kinsenoside inhibits the expression of cathepsin K (CAK),
      dendritic cell-specific transmembrane protein, MMP-9, and TRAP. CONCLUSIONS:
      Kinsenoside inhibits osteoclastogenesis from macrophages by attenuating RANKL
      induced NF-kappaB and NFATc1 activities, which in turn, prevents bone loss from
      OVX mice.

PMID- 23143540
TI  - Dehydroepiandrosterone has strong antifibrotic effects and is decreased in
      idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is an ageing-related lung disorder
      characterised by expansion of the myofibroblast population and aberrant lung
      remodelling. Dehydroepiandrosterone (DHEA), a steroid pro-hormone, decreases with
      age but an exaggerated decline has been associated with chronic degenerative
      diseases. We quantified the plasma levels of DHEA and its sulfated form (DHEA-S)
      in 137 IPF patients and 58 controls and examined the effects of DHEA on human
      lung fibroblasts. Plasma DHEA/DHEA-S was significantly decreased in male IPF
      patients (median (range) DHEA: 4.4 (0.2-29.2) versus 6.7 (2.1-15.2) ng . mL(-1),
      p<0.01; DHEA-S: 47 (15.0-211) versus 85.2 (37.6-247.0) MUg . dL(-1), p<0.001),
      while in females only DHEA-S was significantly decreased (32.6 (15.0-303.0)
      versus 68.3 (16.4-171) MUg . dL(-1), p<0.001). DHEA caused a decrease in
      fibroblast proliferation and an approximately two-fold increase in fibroblast
      apoptosis, probably through the intrinsic pathway with activation of caspase-9.
      This effect was accompanied by upregulation of several pro-apoptotic proteins
      (Bax and cyclin-dependent kinase-inhibitor CDNK1A) and downregulation of anti
      apoptotic proteins, such as cellular inhibitor of apoptosis (c-IAP)1 and c-IAP2.
      DHEA also caused a significant decrease of transforming growth factor-beta1
      induced collagen production and fibroblast to myofibroblast differentiation, and
      inhibited platelet-derived growth factor-induced fibroblast migration. These
      findings demonstrate a disproportionate decrease of DHEA/DHEA-S in IPF patients
      and indicate that this molecule has multiple antifibrotic properties.

PMID- 23143541
TI  - Targeting iron uptake to control Pseudomonas aeruginosa infections in cystic
      fibrosis.
AB  - The aerobic Gram-negative bacterium Pseudomonas aeruginosa is an opportunistic
      pathogen responsible for life-threatening acute and chronic infections in humans.
      As part of chronic infection P. aeruginosa forms biofilms, which shield the
      encased bacteria from host immune clearance and provide an impermeable and
      protective barrier against currently available antimicrobial agents. P.
      aeruginosa has an absolute requirement for iron for infection success. By
      influencing cell-cell communication (quorum sensing) and virulence factor
      expression, iron is a powerful regulator of P. aeruginosa behaviour.
      Consequently, the imposed perturbation of iron acquisition systems has been
      proposed as a novel therapeutic approach to the treatment of P. aeruginosa
      biofilm infection. In this review, we explore the influence of iron availability
      on P. aeruginosa infection in the lungs of the people with the autosomal
      recessive condition cystic fibrosis as an archetypal model of chronic P.
      aeruginosa biofilm infection. Novel therapeutics aimed at disrupting P.
      aeruginosa are discussed, with an emphasis placed on identifying the barriers
      that need to be overcome in order to translate these promising in vitro agents
      into effective therapies in human pulmonary infections. 

PMID- 23143542
TI  - Amelioration of hyperoxia-induced lung injury using a sphingolipid-based
      intervention.
AB  - The aim of this study was to characterise lung function and bronchoalveolar
      lavage sphingolipid profile in newborn mice during hyperoxia exposure and
      recovery in room air, and to examine the effect of d-sphingosine supplementation
      during recovery. Newborn mice were exposed to 80% oxygen for 4 weeks and allowed
      to recover in room air for another 4 weeks. Lung function measurements and
      morphometrical analysis of lung tissue were performed and bronchoalveolar lavage
      fluid was collected during hyperoxia and recovery with and without d-sphingosine
      supplementation. Hyperoxia exposure altered lung function, which partially
      recovered in room air. Lungs had fewer and enlarged alveoli which persisted
      during recovery. Multiple sphingolipids were significantly increased after
      hyperoxia. Ceramides were increased after 2 weeks of recovery, but normalised to
      control values after 4 weeks. The addition of d-sphingosine during the first 5
      days of recovery accelerated the normalisation of ceramide levels at 2 weeks and
      partially reversed the hyperoxia-induced increase in alveolar size and arrest in
      alveolarisation at 4 weeks. Exposure of newborn mice to hyperoxia caused
      restrictive and obstructive lung function changes that partially recovered in
      room air, while alveolar morphology remained abnormal. Hyperoxia increased
      ceramide levels, with normalisation after recovery. d-sphingosine addition during
      recovery reduced ceramide levels and ameliorated hyperoxia-induced alveolar
      arrest. 

PMID- 23143543
TI  - Hyperhomocysteinaemia predicts the decline in pulmonary function in healthy male
      smokers.
AB  - Hyperhomocysteinaemia is associated with chronic obstructive pulmonary disease.
      However, the relationship between plasma homocysteine levels and spirometric
      measures has not been investigated in a general population. We aimed to determine
      whether homocysteine levels are predictive for a rapid decline in lung function
      among healthy current smokers. Blood sampling and spirometry were performed on
      subjects participating in a community-based annual health check in Takahata,
      Japan, from 2004 to 2006 (n=3257). Spirometry was re-evaluated in 147 male
      current smokers in 2009. On initial assessment, forced vital capacity (FVC) %
      predicted and forced expiratory volume in 1 s (FEV1) % predicted correlated
      inversely with homocysteine levels and were predictive for homocysteine levels,
      independent of various clinical factors. Homocysteine levels were higher in
      subjects with restrictive, obstructive or mixed ventilatory disorders. In
      addition, homocysteine levels were higher in subjects with mixed ventilatory
      disorders, compared with restrictive or obstructive disorders. On follow-up,
      subjects showing a decline in FEV1 had higher homocysteine levels than those who
      did not. Logistic regression analysis indicated that homocysteine levels were
      predictive for a decline in FEV1. FVC % pred and FEV1 % pred were significantly
      associated with homocysteine levels, and hyperhomocysteinaemia predicted the
      annual rate of decline in FEV1 among male smokers. 

PMID- 23143544
TI  - Criteria for clinical stability in hospitalised patients with community-acquired
      pneumonia.
AB  - The American Thoracic Society (ATS) and Infectious Diseases Society of America
      (IDSA) suggested two sets of criteria in 2001 and 2007 to define clinical
      stability in community-acquired pneumonia (CAP). The present study aimed to
      evaluate the level of agreement between these two sets of criteria and how well
      they can predict clinical outcomes. A retrospective cohort study was carried out
      of 487 consecutive patients hospitalised with CAP. Level of agreement was tested
      using a survival curve analysis, while prediction of outcomes at 30-day follow-up
      was evaluated through receiver operating characteristic (ROC) analysis. A
      discrepancy between ATS 2001 and ATS/IDSA 2007 criteria in identifying clinical
      stability was detected in 62% of the patients. The median (interquartile range)
      time to clinical stability was 2 (1-4) days based on ATS 2001 and 3 (2-5) days
      based on ATS/IDSA 2007 criteria (p = 0.012). The daily distribution of patients
      who reached clinical stability evaluated with both sets was different (p =
      0.002). The ROC analysis showed an area under the curve of 0.705 for the ATS 2001
      criteria and 0.714 for ATS/IDSA 2007 criteria (p = 0.645). ATS 2001 and ATS/IDSA
      2007 criteria for clinical stability in hospitalised patients with CAP are
      clinically equivalent and both can be used in clinical practice as well as in
      clinical research. 

PMID- 23143545
TI  - Reduced neonatal lung function and wheezing illnesses during the first 5 years of
      life.
AB  - Studies of reduced neonatal lung function and wheezing illnesses during childhood
      show conflicting results. The aim of our study was to assess the association
      between resistance (Rrs) and compliance (Crs) of the respiratory system by using
      the single occlusion technique (SOT) and prospectively collected wheezing
      illnesses during the first 5 years of life in a large birth cohort. SOT was
      performed during natural sleep before the age of 2 months. Information about
      wheezing illnesses was collected from the electronic patient file. 549 infants
      had a successful SOT measurement and complete medical records. Every kPa.L(-1).s(
      1) increase in Rrs was associated with 10% more consultations in the first 3
      years of life. Every 10 mL.kPa(-1) increase in Crs was associated with a 14%
      reduction in consultations in the first 3 years of life, 27% in the fourth to
      fifth years of life, and a lower probability of having asthma at the age of 5
      years (OR 0.66). Children with late-onset or persistent wheezing had significant
      lower Crs values than their peers. An increased neonatal resistance is associated
      with more wheezing illnesses during infancy, while a reduced neonatal compliance
      is associated with more wheezing illnesses during the first 5 years of life, a
      late-onset or persistent wheezing phenotype, and asthma. 

PMID- 23143546
TI  - Outcomes of noncardiac, nonobstetric surgery in patients with PAH: an
      international prospective survey.
AB  - We conducted an international, prospective, 3-year questionnaire-based survey
      among 11 pulmonary hypertension centres to assemble data from patients with
      pulmonary arterial hypertension (PAH) undergoing noncardiac and nonobstetric
      surgery. Data were collected between July 2007 and June 2010 from 114 patients
      with PAH (70% female, mean age 57 years) who underwent major surgery. At the time
      of surgery, 43% were in functional class III/IV. 82% of the interventions were
      performed under general anaesthesia and 18% under spinal anaesthesia. Major
      complications occurred in seven (6.1%) of the patients, of whom four died,
      resulting in an overall perioperative mortality rate of 3.5%. The mortality rate
      was 15% (two out of 13) in emergency procedures, compared with 2% (two out of
      101) in nonemergency procedures (p=0.01). Risk factors for major complications
      were an elevated right atrial pressure (OR 1.1, 95% CI 1.0-1.3; p=0.01), a 6-min
      walking distance <399 m at the last preoperative assessment (OR 2.2, 95% CI 1.1
      3.7; p=0.04), the perioperative use of vasopressors (OR 1.5, 95% CI 1.2-2.7;
      p=0.03) and the need for emergency surgery (OR 2.4, 95% CI 1.4-3.6; p=0.01).
      Major surgery in patients with PAH continues to be a high-risk procedure,
      particularly when emergency interventions are needed.

PMID- 23143547
TI  - Proxy-reported questionnaires for young children with asthma: a structured
      review.
AB  - Which proxy-reported outcome measures have been developed for use with children
      aged 6 years and younger to assess asthma symptoms, asthma control, and asthma
      specific health-related quality of life, and do these questionnaires' measurement
      properties support their use as end-points in clinical trials? A two-phase
      literature search was conducted: 1) studies describing relevant questionnaires
      were identified, and the questionnaires were assessed against predefined
      criteria; 2) studies providing information on the measurement properties of
      questionnaires meeting the predefined inclusion criteria were identified.
      Literature sources included PubMed and EMBASE databases, scientific conference
      proceedings, a clinical trial registry, and a quality of life instrument
      database. The initial search of literature databases and conference abstracts
      identified 631 records. 20 paediatric asthma proxy-reported outcome instruments
      were identified; seven met the inclusion criteria: Childhood Asthma Control Test,
      Control de Asma en Ninos Questionnaire, Pediatric Asthma Caregiver Diary,
      Pediatric Asthma Control Tool, PedsQL 3.0 Short-Form 22 Asthma Module, PedsQL
      Asthma Symptoms Scale, and Test for Respiratory and Asthma Control in Kids. Three
      proxy-reported outcome instruments were considered suitable for use as end-points
      in paediatric asthma clinical trials; the Pediatric Asthma Caregiver Diary
      possesses the strongest measurement properties of the three. 

PMID- 23143548
TI  - Barrier responses of human bronchial epithelial cells to grass pollen exposure.
AB  - The airway epithelium forms a physical, chemical and immunological barrier
      against inhaled environmental substances. In asthma, these barrier properties are
      thought to be abnormal. In this study, we analysed the effect of grass pollen on
      the physical and immunological barrier properties of differentiated human primary
      bronchial epithelial cells. Following exposure to Timothy grass (Phleum pratense)
      pollen extract, the integrity of the physical barrier was not impaired as
      monitored by measuring the transepithelial resistance and immunofluorescence
      staining of tight junction proteins. In contrast, pollen exposure affected the
      immunological barrier properties by modulating vectorial mediator release. CXC
      chemokine ligand (CXCL)8/interleukin (IL)-8 showed the greatest increase in
      response to pollen exposure with preferential release to the apical compartment.
      Inhibition of the extracellular signal-regulated kinase 1/2 and p38 mitogen
      activated protein kinase pathways selectively blocked apical CXCL8/IL-8 release
      via a post-transcriptional mechanism. Apical release of CC chemokine ligand
      (CCL)20/macrophage inflammatory protein-3alpha, CCL22/monocyte-derived chemokine
      and tumour necrosis factor-alpha was significantly increased only in severe
      asthma cultures, while CCL11/eotaxin-1 and CXCL10/interferon-gamma-induced
      protein-10 were reduced in nonasthmatic cultures. The bronchial epithelial
      barrier modulates polarised release of mediators in response to pollen without
      direct effects on its physical barrier properties. The differential response of
      cells from normal and asthmatic donors suggests the potential for the bronchial
      epithelium to promote immune dysfunction in asthma. 

PMID- 23143549
TI  - Clinical assessment for identifying causes of acute respiratory failure in cancer
      patients.
AB  - In cancer patients with acute respiratory failure (ARF), early adequate therapy
      is associated with better outcomes. We investigated the performance of the DIRECT
      approach, which uses criteria available at the bedside at admission to the
      intensive care unit (ICU), to identify causes of ARF in cancer patients. This
      cohort study included cancer patients with ARF of determined aetiology.
      Associations of aetiological groups with the selected criteria were evaluated
      using correspondence analysis. 424 cancer patients were included: 201 (47%) with
      bacterial pneumonia, 131 (31%) with opportunistic infections and 92 (22%) with
      noninfectious disorders. Mechanical ventilation (both invasive and noninvasive)
      was needed in 328 (77%) patients, treatment for shock in 217 (51%) patients and
      dialysis in 82 (19%) patients. 142 (34%) patients died in the ICU. Correspondence
      plots showed that bacterial pneumonia was associated with neutropenia, solid
      tumour, multiple myeloma, <3 days since symptom onset, shock, unilateral crackles
      and unilateral radiographic pattern. Opportunistic infections were associated
      with steroids, lymphoproliferative disorders and haematopoietic stem-cell
      transplantation, whereas noninfectious disorders were associated with acute
      leukaemia The selected criteria are strongly associated with causes of ARF in
      cancer patients and could be used to develop an algorithm for selecting first
      line diagnostic investigations and empirical treatments. 

PMID- 23143550
TI  - Resting heart rate is a predictor of mortality in COPD.
AB  - The clinical significance of high heart rate in chronic obstructive pulmonary
      disease (COPD) is unexplored. We investigated the association between resting
      heart rate, pulmonary function, and prognosis in subjects with COPD. 16 696
      subjects aged >=40 years from the Copenhagen City Heart Study, a prospective
      study of the general population, were followed for 35.3 years, 10 986 deaths
      occurred. Analyses were performed using time-dependent Cox-models and net
      reclassification index (NRI). Resting heart rate increased with severity of COPD
      (p<0.001). Resting heart rate was associated with both cardiovascular and all
      cause mortality across all stages of COPD (p<0.001). Within each stage of COPD,
      resting heart rate improved prediction of median life expectancy; the difference
      between <65 bpm and >85 bpm was 5.5 years without COPD, 9.8 years in mild (Global
      Initiative for Chronic Obstructive Lung Disease (GOLD) stage I), 6.7 years in
      moderate (GOLD stage II) and 5.9 years in severe/very severe COPD (GOLD stage
      III/IV), (p<0.001). Resting heart rate significantly improved risk prediction
      when added to GOLD stage (categorical NRI 4.9%, p = 0.01; category less NRI
      23.0%, p<0.0001) or forced expiratory volume in 1 s % predicted (categorical NRI
      7.8%, p = 0.002; category less NRI 24.1%, p<0.0001). Resting heart rate increases
      with severity of COPD. Resting heart rate is a readily available clinical
      variable that improves risk prediction in patients with COPD above and beyond
      that of pulmonary function alone. Resting heart rate may be a potential target
      for intervention in COPD. 

PMID- 23143551
TI  - Traffic-related air pollution is related to interrupter resistance in 4-year-old
      children.
AB  - Outdoor air pollution has been associated with decrements in lung function and
      growth of lung function in school-age children. Lung function effects have not
      been examined in preschoolers, with the exception of one study on minute
      ventilation in newborns. Our goal was to assess the relationship between long-
      and short-term exposure to traffic-related air pollution and interrupter
      resistance in 4-year-old children. Lung function was measured using the
      interrupter resistance method in children participating in a Dutch birth cohort
      study. Long-term average air pollution concentrations of fine particulate matter,
      nitrogen dioxide and soot at the residential address at birth were assessed using
      land-use regression models. Daily average air pollution concentrations on the day
      of clinical examination were obtained from the Dutch National Air Quality
      Monitoring Network. Significant associations were found between long-term average
      air pollution concentrations and interrupter resistance. Interrupter resistance
      increased by 0.04 kPa.s.L(-1) (95% CI 0.01-0.07) per interquartile range increase
      (3.3 MUg.m(-3)) in fine particle concentration. Short-term exposure was not
      associated with interrupter resistance. Long-term exposure to traffic-related air
      pollution was associated with increased interrupter resistance in 4-year-old
      children, supporting previous birth cohort studies reporting effects of air
      pollution on subjectively reported respiratory symptoms in preschool children.

PMID- 23143552
TI  - Age and height dependence of lung clearance index and functional residual
      capacity.
AB  - The lung clearance index (LCI) is more sensitive than spirometry in detecting
      abnormal lung function in children with cystic fibrosis. LCI is thought to be
      independent of age, but recent evidence suggests that the upper limit of normal
      is higher in infants and preschool children than in older subjects. This study
      examines whether LCI remains independent of body size throughout childhood.
      Multiple-breath washout data from healthy children and adolescents were collated
      from three centres using the mass spectrometer system and the inert gas sulfur
      hexafluoride. Reference equations for LCI and functional residual capacity (FRC)
      were constructed using the LMS (lambda-mu-sigma) method. Data were available from
      497 subjects (2 weeks to 19 years of age) tested on 659 occasions. LCI was
      dependent on body size, decreasing in a nonlinear pattern as height increased.
      Changes were particularly marked in the first 5 years of life. Height, age and
      sex were all independent predictors of FRC. Minimal between-centre differences
      allowed unified reference equations to be developed. LCI is not independent of
      body size. Although a constant upper normal limit would suffice for cross
      sectional clinical assessments from 6 years of age, appropriate reference
      equations are essential for accurate interpretation of results during early
      childhood.

PMID- 23143553
TI  - Interstitial lung disease in clinically amyopathic dermatomyositis (CADM)
      patients: a retrospective study of 41 Chinese Han patients.
AB  - To study the clinical features and associated risk factors of interstitial lung
      disease (ILD) in clinically amyopathic dermatomyositis (CADM) in Chinese
      patients. Forty-one Chinese Han patients with a diagnosis of CADM in West China
      Hospital from August 2008 to 2011 were retrospectively analyzed. The prevalence
      of ILD in CADM patients is 60.98 %, in which 26.83 % for acute/subacute
      interstitial pneumonia (A/SIP) and 34.15 % for chronic interstitial pneumonia
      (CIP). Mortality of A/SIP is 63.64 %, with a 6-month survival rate of 54.50 %.
      Levels of erythrocyte sedimentation rate, serum ferritin, alanine
      aminotransferase, aspartate aminotransferase, creatine kinase, lactate
      dehydrogenase, hydroxybutyric dehydrogenase, and immunoglobulin A (IgA) are
      higher in CADM-ILD patients than CADM patients without ILD. Levels of serum ALB
      and lymphocyte count in peripheral blood are significant lower in A/SIP than in
      CIP group. Sign of ground glass opacities in high-resolution computed tomography
      (HRCT) images is more common in A/SIP group, and diffusion function is worse in
      these patients compared with CIP group. The prevalence of ILD in Chinese CADM
      patients is strikingly high, and A/SIP is a major cause of death in CADM
      patients. Laboratory findings combined with HRCT examination and pulmonary
      function tests can provide valuable predictive information of ILD or A/SIP in
      CADM patients.

PMID- 23143554
TI  - Clinically silent Crohn's disease in a patient with Takayasu's arteritis
      unresponsive to conventional therapies.
AB  - Takayasu arteritis (TA) and Crohn's disease (CD) are chronic inflammatory
      diseases with granulomatous nature. Here, we report a case of TA with a silent
      course of CD who was refractory to corticosteroid and immunosuppressive
      treatments and improved with adalimumab therapy. 

PMID- 23143555
TI  - Effect of cyclophosphamide on cytokines in patients with primary Sjogren's
      syndrome-associated interstitial lung disease in South China.
AB  - The objective of the study is to investigate the mechanisms of cyclophosphamide
      sequential therapy for patient with primary Sjogren's syndrome-associated
      interstitial lung disease (PSS-ILD). This was a retrospective review of 15
      patients (2005-2008) with PSS-ILD who underwent cyclophosphamide sequential
      therapy. Peripheral blood and bronchoalveolar lavage (BALF) were obtained before
      and 3, 6, 12 and 24 months after the treatment. The TNF-alpha and TGF-beta1 mRNA
      levels in peripheral blood were measured using reverse transcription polymerase
      chain reaction. Serum and BALF TNF-alpha, TGF-beta1 and MMP-9 levels were
      measured using sandwich enzyme-linked immunosorbent assay. The average levels of
      serum TNF-alpha (0.39 +/- 0.22) and TGF-beta1 (0.31 +/- 0.18) mRNA in patients
      with PSS-ILD were higher compared with that in patients with PSS without ILD. TNF
      alpha level (0.23 +/- 0.19) was significantly decreased 3 months after
      cyclophosphamide treatment (t = 2.533, p < 0.05), and TGF-beta1 (0.31 +/- 0.18)
      level markedly decreased after 6 months of treatment (t = 2.617, p < 0.05). The
      levels of serum TNF-alpha (11.2 +/- 2.6) MUg/L, TGF-beta1 (72 +/- 19) MUg/L and
      MMP-9 (38 +/- 9) MUg/L in patients with PSS-ILD were higher than that in patients
      with PSS without ILD. TGF-beta1 (36 +/- 12) MUg/L level decreased significantly
      after 3 months of treatment (t = 2.526, p < 0.05), and TNF-alpha level (7.1 +/-
      1.3) MUg/L markedly decreased after 6 months of therapy (t = 2.578, p < 0.05).
      MMP-9 level (18 +/- 4) MUg/L decreased significantly after 12-month treatment (t
      = 2.329, p < 0.05). The levels of BALF TNF-alpha (17.1 +/- 3.5) MUg/L, TGF-beta1
      (36 +/- 17) MUg/L and MMP-9 (27 +/- 10) MUg/L in patients with PSS-ILD were
      higher than that in patients with PSS without ILD. TGF-beta1 (21 +/- 14) MUg/L
      level decreased significantly after 3-month treatment, and TNF-alpha level (9.4
      +/- 1.7) MUg/L was decreased after 6 months of cyclophosphamide treatment that
      may be associated with its inhabitation on production of TNF-alpha, TGF-beta1 and
      MMP-9.

PMID- 23143556
TI  - Elevated serum levels of high mobility group box protein 1 (HMGB1) in patients
      with ankylosing spondylitis and its association with disease activity and quality
      of life.
AB  - This study was carried out to determine the serum levels of high mobility group
      box protein 1 (HMGB1) in patients with ankylosing spondylitis (AS) and to
      evaluate its correlation with disease activity and quality of life. According to
      our knowledge, it is the first trial evaluating HMGB1 levels in AS. Serum samples
      of 30 patients (18 males and 12 females) with AS and 29 healthy controls (HC) (15
      females and 14 males) were collected. HMGB1 levels were measured by enzyme-linked
      immunosorbent assay, activity of disease was assessed according to the Bath AS
      Disease Activity Index (BASDAI), and functional status of patients was evaluated
      with Bath AS Functional Index (BASFI). Modified Schober, chest expansion values
      and AS Quality of Life Questionnaire (ASQoL) scores were noted. The serum levels
      of HMGB1 were obtained significantly increased in AS patients compared to HC (p <
      0.05). There was no significant correlation between HMGB1 levels and ESR (p >
      0.05), and CRP (p > 0.05) values. BASDAI, BASFI and ASQoL scores were also not
      correlated with serum levels of HMGB1 (p > 0.05). Our results suggest that HMGB1
      might play an important role in the pathogenesis of AS; however, it seems not to
      be a good candidate for reflecting disease activity, functional abilities and the
      quality of life in patients with AS; on the other hand, the increased levels of
      HMGB1 in patients may open a new dimension for targeting this cytokine as a new
      therapy option in AS.

PMID- 23143557
TI  - Bisphosphonates or prostacyclin in the treatment of bone-marrow oedema syndrome
      of the knee and foot.
AB  - Bone-marrow oedema (BME) represents a reversible but mostly painful increase in
      interstitial fluid. The exact pathogenetic processes still remain unknown.
      Treatment options are mainly symptomatic with core decompression as golden
      standard leading to immediate pain relieve. Recently, it has been shown that
      intravenous prostacyclin and bisphosphonates are useful in achieving a reduction
      in BME with a considerable improvement in the accompanying symptoms. We compared
      the outcome of both intravenously applied prostacyclin (Ilomedin((r)), 10
      patients) and bisphosphonate (Bondronat((r)), 10 patients) in treatment of BME of
      the knee and foot. We could find a significant improvement of WOMAC score, SF-36
      score and VAS 3 months and 1 year after therapeutic intervention in both the
      prostacyclin and the bisphosphonate group. Concerning the MRI scans in both
      groups, we found a distinct reduction of BME in 47 % and a complete regression in
      40 %. Comparing both groups, the improvement of the scores was greater in the
      prostacyclin group than in the bisphosphonate group; the difference, however, was
      not significant. Intravenous bisphosphonates as well as prostacyclin are of
      efficient therapeutic benefit in treatment of BME with a quicker and greater
      effect of prostacyclin.

PMID- 23143558
TI  - Estradiol regulates miR-135b and mismatch repair gene expressions via estrogen
      receptor-beta in colorectal cells.
AB  - Estrogen has anti-colorectal cancer effects which are thought to be mediated by
      mismatch repair gene (MMR) activity. Estrogen receptor (ER) expression is
      associated with microRNA (miRNA) expression in ER-positive tumors. However,
      studies of direct link between estrogen (especially estradiol E2), miRNA
      expression, and MMR in colorectal cancer (CRC) have not been done. In this study,
      we first evaluated the effects of estradiol (E2) and its antagonist ICI182,780 on
      the expression of miRNAs (miR-31, miR-155 and miR-135b) using COLO205, SW480 and
      MCF-7 cell lines, followed by examining the association of tissue miRNA
      expression and serum E2 levels using samples collected from 18 colorectal cancer
      patients. E2 inhibited the expressions of miRNAs in COLO205 cells, which could be
      reversed by E2 antagonist ICI 182.780. The expression of miR-135b was inversely
      correlated with serum E2 level and ER-beta mRNA expression in CRC patients'
      cancer tissues. There were significant correlations between serum E2 level and
      expression of ER-beta, miR-135b, and MMR in colon cancer tissue. This study
      suggests that the effects of estrogen on MMR function may be related to
      regulating miRNA expression via ER-beta, which may be the basis for the anti
      cancer effect in colorectal cells.

PMID- 23143560
TI  - The facial nerve canal in patients with Bell's palsy: an investigation by high
      resolution computed tomography with multiplanar reconstruction.
AB  - Facial nerve edema is an important finding in Bell's palsy patients. Inflammation
      may cause facial nerve edema, and mechanical compression and ischemic change of
      the facial nerve may occur in the facial nerve canal. A few studies have reported
      the dimensions of the facial nerve canal using conventional computed tomography
      or human temporal bone sections. However, the cross-sectional area of the facial
      nerve canal has not been fully understood. Therefore, the cross-sectional area of
      the facial nerve canal was measured in patients with unilateral Bell's palsy by
      computer tomography with multiplanar reconstruction. Sixteen patients with
      unilateral Bell's palsy were enrolled. Computed tomography of the temporal bone
      was performed, and perpendicular images to the facial nerve canal were
      reconstructed by the multiplanar reconstruction technique. The cross-sectional
      area of the facial nerve canal on the affected and unaffected sides was measured
      at the labyrinthine segment, the horizontal segment, and the mastoid segment.
      Both in the labyrinthine and horizontal segments, the mean cross-sectional area
      of the facial nerve canal was significantly smaller on the affected side than on
      the unaffected side. There was no significant difference between the affected and
      unaffected sides in the cross-sectional area of the facial nerve canal in the
      mastoid segment. The labyrinthine segment was the narrowest segment in the facial
      nerve canal. These findings suggest that the facial nerve is vulnerable,
      especially in the labyrinthine segment of the facial nerve canal, and a narrow
      facial nerve canal may be one of the risk factors for Bell's palsy.

PMID- 23143559
TI  - Human skeletal dysplasia caused by a constitutive activated transient receptor
      potential vanilloid 4 (TRPV4) cation channel mutation.
AB  - The transient receptor potential vanilloid 4 (TRPV4) cation channel, a member of
      the TRP vanilloid subfamily, is expressed in a broad range of tissues where it
      participates in the generation of Ca2+ signals and/or depolarization of the
      membrane potential. Regulation of TRPV4 abundance at the cell surface is critical
      for osmo- and mechanotransduction. Defects in TRPV4 are the cause of several
      human diseases, including brachyolmia type 3 (MIM:113500) (also known as
      brachyrachia or spondylometaphyseal dysplasia Kozlowski type [MIM:118452]), and
      metatropic dysplasia (MIM:156530) (also called metatropic dwarfism or
      parastremmatic dwarfism [MIM:168400]). These bone dysplasia mutants are
      characterized by severe dwarfism, kyphoscoliosis, distortion and bowing of the
      extremities, and contractures of the large joints. These diseases are
      characterized by a combination of decreased bone density, bowing of the long
      bones, platyspondyly, and striking irregularities of endochondral ossification
      with areas of calcific stippling and streaking in radiolucent epiphyses,
      metaphyses, and apophyses. In this review, we discuss the potential effect of the
      mutation on the regulation of TRPV4 functions, which are related to human
      diseases through deviated function. In particular, we emphasize how the
      constitutive active TRPV4 mutant affects endochondral ossification with a reduced
      number of hypertrophic chondrocytes and the presence of cartilage islands within
      the zone of primary mineralization. In addition, we summarize current knowledge
      about the role of TRPV4 in the pathogenesis of several diseases.

PMID- 23143562
TI  - Electrical properties and impedance spectroscopy of pure and copper-oxide-added
      potassium sodium niobate ceramics.
AB  - Pure and 1 mol% CuO-added lead-free potassium sodium niobate K0.5Na0.5NbO3 (KNN)
      ceramics were prepared by the conventional solid-state calcination method. Copper
      oxide was mainly used as a sintering aid in the KNN structure. Microstructural
      analyses clearly showed that the CuO formed a secondary phase at the grain
      boundaries. Impedance spectroscopy was used as a tool to analyze the electrical
      behavior of KNN ceramics as a function of frequency from 100 Hz to 10 MHz at
      various temperatures. The impedance studies proved that CuO led to the formation
      of a secondary grain boundary phase, as well as creation of highly mobile point
      defects. The relaxation time of copper-added samples was less than that of pure
      KNN. This shorter time indicated a higher space charge mobility for CuO-added
      samples. The thermal activation energy for relaxation of charge carriers (Eg) was
      calculated as 0.73 eV for CuO-added samples.

PMID- 23143561
TI  - Short-term hearing results after primary stapedotomy with nitinol and teflon
      platinum prostheses for otosclerosis.
AB  - The aim of this study is to determine differences in postoperative air-bone gap
      (ABG) after placement of teflon-platinum or nitinol middle ear prostheses in
      primary stapedotomy patients with otosclerosis. Thirty otosclerosis patients (24
      female, 6 male; age 10-61 years) with primary stapedotomy were studied
      prospectively. Before and after surgery, the mean and standard deviations of the
      ABG were measured at eight frequencies (0.25-4 kHz). Patients were randomized
      into one of two groups receiving either teflon-platinum or nitinol prostheses.
      Hearing results were assessed 1 year after surgery. To assess the joint influence
      of treatment and frequency on ABG reduction, a linear mixed model was used
      (significance level was p = 5%). The Tukey-Kramer method was used to adjust for
      multiple comparisons. Significant differences were found between treatment groups
      (p < 0.0001) and between frequencies within the same treatment group (p < 0.0001)
      but no interaction (p = 0.7963), i.e. the reduction of the conductive components
      over frequencies was nearly parallel in both groups. Overall, patients in the
      Teflon group had a larger reduction of conductive components, on average 8.0 dB
      more reduction, than patients in the nitinol group. However, after adjusting for
      multiple comparisons, we could not identify a single frequency with a significant
      difference in reduction of conductive components. Use of the teflon-platinum
      prosthesis results in statistically non-significant better ABG closure at 0.25-4
      kHz 1 year postoperatively than the use of the nitinol prosthesis.

PMID- 23143563
TI  - Power enhancement of piezoelectric transformers by adding heat transfer
      equipment.
AB  - It is known that piezoelectric transformers have several inherent advantages
      compared with conventional electromagnetic transformers. However, the maximum
      power capacity of piezoelectric transformers is not as large as electromagnetic
      transformers in practice, especially in the case of high output current. The
      theoretical power density of piezoelectric transformers calculated by stress
      boundary can reach 330 W/cm(3), but no piezoelectric transformer has ever reached
      such a high power density in practice. The power density of piezoelectric
      transformers is limited to 33 W/cm(3) in practical applications. The underlying
      reason is that the maximum passing current of the piezoelectric material
      (mechanical current) is limited by the temperature rise caused by heat
      generation. To increase this current and the power capacity, we proposed to add a
      thermal pad to the piezoelectric transformer to dissipate heat. The experimental
      results showed that the proposed techniques can increase by 3 times the output
      current of the piezoelectric transformer. A theoretical-phenomenological model
      which explains the relationship between vibration velocity and generated heat is
      also established to verify the experimental results.

PMID- 23143564
TI  - Active suppression of a beam under a moving mass using a pointwise fiber Bragg
      grating displacement sensing system.
AB  - This paper investigates active vibration control of a beam under a moving mass
      using a pointwise fiber Bragg grating (FBG) displacement sensing system. Dynamic
      responses of the proposed FBG displacement sensor are demodulated with an FBG
      filter and verified with measurement results obtained from a noncontact fiber
      optic displacement sensor. System identification of the beam is first performed
      with a piezoceramic actuator and positive position feedback (PPF) controllers are
      designed based on the identified results. Then, transient responses of the beam
      under a moving mass with different moving conditions are measured using the FBG
      displacement sensor. A high-speed camera is used to detect the speed of the
      moving mass for further discussions about its influence on the transient
      response. Finally, active vibration control of the beam under the moving mass is
      performed and fast Fourier transform (FFT) as well as short-time Fourier
      transform (STFT) are employed to demonstrate control performances. For the case
      in which a rolling steel ball is directed from a slide to the beam to generate
      the moving mass, reductions of the vibration up to 50% and 60% are achieved in
      the frequency domain for the first and second modes of the beam, respectively.
      Based on the control experiments on the smallscale beam, results in this work
      show that the proposed FBG displacement sensing system can be used in research on
      the moving mass problem.

PMID- 23143565
TI  - Optimizing frequency and pulse shape for ultrasound current source density
      imaging.
AB  - Electric field mapping is commonly used to identify irregular conduction pathways
      in the heart (e.g., arrhythmia) and brain (e.g., epilepsy). Ultrasound current
      source density imaging (UCSDI), based on the acoustoelectric (AE) effect, is a
      promising new technique for mapping electrical current in four dimensions with
      enhanced resolution. The frequency and pulse shape of the ultrasound beam affect
      the sensitivity and spatial resolution of UCSDI. In this study, we explore the
      effects of ultrasound transducer frequency bandwidth and coded excitation pulses
      for UCSDI and the inherent tradeoff between sensitivity and spatial resolution.
      We used both simulations and bench-top experiments to image a time-varying
      electrical dipole in 0.9% NaCl solution. To study the effects of ultrasound
      bandwidth, we chose two ultrasound transducers with different center frequencies
      (1.0 and 2.25 MHz). For coded excitation, we measured the AE voltage signal with
      different chirp excitations. As expected, higher bandwidth correlated with
      improved spatial resolution at the cost of sensitivity. On the other hand, chirp
      excitation significantly improved sensitivity (3.5 MUV/mA) compared with
      conventional square pulse excitation (1.6 MUV/mA) at 1 MHz. Pulse compression
      achieved spatial resolution similar to that obtained using square pulse
      excitation, demonstrating enhanced detection sensitivity without loss of
      resolution. Optimization of the time duration of the chirp pulse and frequency
      sweep rate can be further used to improve the quality of UCSDI.

PMID- 23143567
TI  - Real-time 1-D/2-D transient elastography on a standard ultrasound scanner using
      mechanically induced vibration.
AB  - Transient elastography has been well established in the literature as a means of
      assessing the elasticity of soft tissue. In this technique, tissue elasticity is
      estimated from the study of the propagation of the transient shear waves induced
      by an external or internal source of vibration. Previous studies have focused
      mainly on custom single-element transducers and ultrafast scanners which are not
      available in a typical clinical setup. In this work, we report the design and
      implementation of a transient elastography system on a standard ultrasound
      scanner that enables quantitative assessment of tissue elasticity in real-time.
      Two new custom imaging modes are introduced that enable the system to image the
      axial component of the transient shear wave, in response to an externally induced
      vibration, in both 1-D and 2-D. Elasticity reconstruction algorithms that
      estimate the tissue elasticity from these transient waves are also presented.
      Simulation results are provided to show the advantages and limitations of the
      proposed system. The performance of the system is also validated experimentally
      using a commercial elasticity phantom.

PMID- 23143566
TI  - Intravascular ultrasound catheter to enhance microbubble-based drug delivery via
      acoustic radiation force.
AB  - Previous research has demonstrated that acoustic radiation force enhances
      intravascular microbubble adhesion to blood vessels in the presence of flow for
      moleculartargeted ultrasound imaging and drug delivery. A prototype acoustic
      radiation force intravascular ultrasound (ARFIVUS) catheter was designed and
      fabricated to displace a microbubble contrast agent in flow representative of
      conditions encountered in the human carotid artery. The prototype ARFIVUS
      transducer was designed to match the resonance frequency of 1.4- to 2.6-MUm
      diameter microbubbles modeled by an experimentally verified 1-D microbubble
      acoustic radiation force translation model. The transducer element was an
      elongated Navy Type I (hard) lead zirconate titanate (PZT) ceramic designed to
      operate at 3 MHz. Fabricated devices operated with center frequencies of 3.3 and
      3.6 MHz with -6-dB fractional bandwidths of 55% and 50%, respectively.
      Microbubble translation velocities as high as 0.86 m/s were measured using a high
      speed streak camera when insonating with the ARFIVUS transducer. Finally, the
      prototype was used to displace microbubbles in a flow phantom while imaging with
      a commercial 45-MHz imaging IVUS transducer. A sustained increase of 31 dB in
      average video intensity was measured following insonation with the ARFIVUS,
      indicating microbubble accumulation resulting from the application of acoustic
      radiation force.

PMID- 23143568
TI  - Applying Thomson's multitaper approach to reduce speckle in medical ultrasound
      imaging.
AB  - To reduce the variance of speckle in coherent imaging systems, one must average
      images with different speckle realizations. Traditionally, these images have been
      formed by observing the target region from slightly different angles (spatial
      compounding) or by varying the involved temporal frequencies (frequency
      compounding). In this paper, we investigate a third option based on Thomson's
      multitaper approach to power spectrum estimation. The tapers are applied
      spatially, as array weights. Our investigations, based on both recorded
      ultrasound data and simulations, verify that the multitaper approach can be used
      for speckle reduction at a rate comparable to that of the more traditional method
      of spatial compounding. Because of the spectral concentration of the tapers, an
      added benefit is reduced side lobe levels, which can result in steeper edges and
      better definition of cyst-like structures.

PMID- 23143569
TI  - Ultrasound time-reversal MUSIC imaging with diffraction and attenuation
      compensation.
AB  - Time-reversal imaging with multiple signal classification (TR-MUSIC) is an
      algorithm for imaging point-like scatterers embedded in a homogeneous and non
      attenuative medium. We generalize this algorithm to account for the attenuation
      in the medium and the diffraction effects caused by the finite size of the
      transducer elements. The generalized algorithm yields higher-resolution images
      than those obtained with the original TR-MUSIC algorithm. We evaluate the axial
      and lateral resolutions of the images obtained with the generalized algorithm
      when noise corrupts the recorded signals and show that the axial resolution is
      degraded more than the lateral resolution. The TR-MUSIC algorithm is valid only
      when the number of point-like targets in the imaging plane is fewer than the
      number of transducer elements used to interrogate the medium. We remedy this
      shortcoming by dividing the imaging plane into subregions and applying the TR
      MUSIC algorithm to the windowed backscattered signals corresponding to each
      subregion. The images of all subregions are then combined to form the total
      image. Imaging results of numerical and phantom data show that when the number of
      scatterers within each subregion is much smaller than the number of transducer
      elements, the windowing method yields super-resolution images with accurate
      scatterer localization. We use computer simulations and tissue-mimicking phantom
      data acquired with a real-time synthetic-aperture ultrasound system to illustrate
      the algorithms presented in the paper.

PMID- 23143570
TI  - An open system for intravascular ultrasound imaging.
AB  - Visualization of the blood vessels can provide valuable morphological information
      for diagnosis and therapy strategies for cardiovascular disease. Intravascular
      ultrasound (IVUS) is able to delineate internal structures of vessel wall with
      fine spatial resolution. However, the developed IVUS is insufficient to identify
      the fibrous cap thickness and tissue composition of atherosclerotic lesions.
      Novel imaging strategies have been proposed, such as increasing the center
      frequency of ultrasound or using a modulated excitation technique to improve the
      accuracy of diagnosis. Dual-mode tomography combining IVUS with optical
      tomography has also been developed to determine tissue morphology and
      characteristics. The implementation of these new imaging methods requires an open
      system that allows users to customize the system for various studies. This paper
      presents the development of an IVUS system that has open structures to support
      various imaging strategies. The system design is based on electronic components
      and printed circuit board, and provides reconfigurable hardware implementation,
      programmable image processing algorithms, flexible imaging control, and raw RF
      data acquisition. In addition, the proposed IVUS system utilized a miniaturized
      ultrasound transducer constructed using PMNPT single crystal for better
      piezoelectric constant and electromechanical coupling coefficient than
      traditional lead zirconate titanate (PZT) ceramics. Testing results showed that
      the IVUS system could offer a minimum detectable signal of 25 MUV, allowing a 51
      dB dynamic range at 47 dB gain, with a frequency range from 20 to 80 MHz.
      Finally, phantom imaging, in vitro IVUS vessel imaging, and multimodality imaging
      with photoacoustics were conducted to demonstrate the performance of the open
      system.

PMID- 23143571
TI  - Aberration compensation of an ultrasound imaging instrument with a reduced number
      of channels.
AB  - Focusing and imaging qualities of an ultrasound imaging system that uses
      aberration correction were experimentally investigated as functions of the number
      of parallel channels. Front-end electronics that consolidate signals from
      multiple physical elements can be used to lower hardware and computational costs
      by reducing the number of parallel channels. However, the signals from sparse
      arrays of synthetic elements yield poorer aberration estimates. In this study,
      aberration estimates derived from synthetic arrays of varying element sizes are
      evaluated by comparing compensated receive focuses, compensated transmit focuses,
      and compensated b-scan images of a point target and a cyst phantom. An array of
      80 x 80 physical elements with a pitch of 0.6 x 0.6 mm was used for all of the
      experiments and the aberration was produced by a phantom selected to mimic
      propagation through abdominal wall. The results show that aberration correction
      derived from synthetic arrays with pitches that have a diagonal length smaller
      than 70% of the correlation length of the aberration yield focuses and images of
      approximately the same quality. This connection between correlation length of the
      aberration and synthetic element size provides a guideline for determining the
      number of parallel channels that are required when designing imaging systems that
      employ aberration correction.

PMID- 23143572
TI  - Scale transform signal processing for optimal ultrasonic temperature
      compensation.
AB  - In structural health monitoring, temperature compensation is an important step to
      reduce systemic errors and avoid false-positive results. Several methods have
      been developed to accomplish temperature compensation in guided wave systems, but
      these techniques are often limited in computational speed. In this paper, we
      present a new methodology for optimal, stretch-based temperature compensation
      that operates on signals in the stretch factor and scale-transform domains. Using
      these tools, we demonstrate three algorithms for temperature compensation that
      show improved computational speed relative to other optimal methods. We test the
      performance of these algorithms using experimental guided wave data.

PMID- 23143573
TI  - Narrowband ultrasonic detection with high range resolution: separating echoes via
      compressed sensing and singular value decomposition.
AB  - It is well known that broader bandwidth leads to higher range resolution, but in
      ultrasonic flaw detection, the bandwidth is often limited. That is, the upper
      frequency of the transmitted signal is bounded by the attenuation of high
      frequency ultrasound, especially when the penetration depth is large. In this
      case, only the band-limited signals are suitable for far-field detection.
      Fortunately, theoretical analysis in this paper shows that narrowband detection
      has greater potential for obtaining high range resolution compared with broadband
      detection. However, it is difficult to fully utilize this potential because of
      the severe overlap of narrowband echoes. As a result, we propose a novel approach
      for separating highly overlapping narrowband echoes in this paper to improve the
      resolution of range imaging. In our approach, in addition to a formulation
      following the emerging theory of sparse representation and compressed sensing,
      singular value decomposition is also employed to capture the main features of the
      signals, making this approach robust to moderate signal distortions. Numerous
      simulations and experiments on real data show that the proposed approach is able
      to fully utilize the potential of narrowband detection and outperforms other
      competitive methods in terms of stability and accuracy.

PMID- 23143574
TI  - A polyimide-etalon thin film structure for all-optical high-frequency ultrasound
      transduction.
AB  - In this work, we have designed, fabricated, and tested an all-optical ultrasound
      transducer by integrating a photoabsorptive polyimide thin film into a Fabry
      Perot (etalon) high-frequency receiver. A 5-ns UV pulse was used for
      thermoelastic ultrasound generation in the polyimide film, and the transmission
      had a maximum amplitude of 4.3 MPa centered at 27 MHz with a fractional bandwidth
      of 107%. The device attained a noise-equivalent pressure of 1.3 Pa/?Hz in receive
      only mode. When used in pulse-echo mode, the -6-dB upper cutoff frequency of the
      transmit/receive response reached 47 MHz. Basic imaging capabilities were also
      investigated by scanning the near-infrared probe beam across the device to create
      a 2 * 2 mm synthetic aperture. The imaging of targets placed at depths of 1.8 and
      5.2 mm yielded estimates of 71 and 145 MUm, respectively, for the lateral
      resolution and 35 and 38 MUm, respectively, for the axial resolution. Finally, a
      design concept for a forward-viewing intravascular imager is presented that
      entails the coupling of light to a rotating, linear array of optical fibers on
      top of which are deposited polyimide-etalon transducers. Such a design would
      allow for a flexible and compact high-resolution imager well-suited for
      intravascular applications, such as guidance of treatment in the case of chronic
      total occlusion.

PMID- 23143575
TI  - Acoustically coupled thickness-mode AIN-on-Si band-pass filters--part I:
      principle and devices.
AB  - In this, the first of two papers, we present the working principle and the
      implementation of laterally acoustically coupled thickness-mode thin-film
      piezoelectric-on-substrate (TPoS) filters. This type of filter offers low
      insertion loss and small bandwidth in a broad frequency range--from a few hundred
      megahertz up to a few gigahertz--and occupy a small chip area. In this paper, we
      discuss several design concerns, including the choice of materials for TPoS
      filters. We demonstrate a design for an air-suspended AlN-on-Si filter, which
      offers a low insertion loss of 2.4 dB at 2.877 GHz. The bandwidth of this filter
      is 12 MHz with a return loss of better than 30 dB. In Part II of this paper, we
      present a comprehensive analysis of the effect of physical layout parameters on
      the frequency response of TPoS filters.

PMID- 23143576
TI  - Acoustically coupled thickness-mode AIN-on-Si band-pass filters--part II:
      simulation and analysis.
AB  - In this, the second of two papers, we present numerical simulations and
      comprehensive analysis of acoustically coupled thickness-mode AlN-on-Si filters.
      We simulate the scattering parameters of such acoustically coupled filters using
      commercially available finite element analysis software and compare the
      simulation results with a set of measurements. The simulations are in good
      agreement with the measurements, allowing the optimization of filter
      characteristics. We analyze the filter response under varying geometric
      parameters and demonstrate that variations in the top electrode geometry allow
      the design of low-loss filters (insertion loss <5 dB) with percentage bandwidth
      up to about 1% and ripple less than 1 dB.

PMID- 23143577
TI  - The fifth-order overtone vibrations of quartz crystal plates with corrected
      higher-order Mindlin plate equations.
AB  - Higher-order overtone resonators have been widely used in various electronic
      products for their higher vibration frequencies, which are in the much-needed
      frequency range beyond the reach of the fundamental mode. However, the existing
      designs of higher-order overtone resonators and further improvement for meeting
      more precise requirements are largely based on empirical approaches. As an
      analytical effort, we have derived the corrected fifth-order Mindlin plate
      equations with the consideration of electric potential and overtone
      displacements. The elimination and truncation of the infinite two-dimensional
      equations has been done to ensure the exact cut-off frequencies of the
      fundamental, the third-order overtone, and fifth-order overtone thickness-shear
      modes in comparison with the three-dimensional equations. The frequency spectra
      are plotted in the vicinity of overtone thickness-shear modes for analysis of
      couplings and interactions with spurious modes, and the optimal design of quartz
      crystal blanks for overtone vibrations has been suggested. The equations,
      solutions, and method will be important in design of the higher-order overtone
      thickness-shear vibration resonators.

PMID- 23143578
TI  - Modeling the measurement of ultrasonic beams transmitted through a penetrable
      acoustic cone.
AB  - The interaction of ultrasonic beams with conical scatterers is governed by a
      combination of diffraction effects occurring at the aperture of the acoustic
      source/receiver and refraction through the cone. Accordingly, the outcome of a
      transmission experiment is dependent upon the many physical parameters
      characterizing the transducers and the cone. We develop a simplified model which
      describes the deflection caused by refraction through the cone using ray theory,
      then uses Huygens' summation to calculate the transducer response from this
      deflection. The model's accuracy is verified by comparison to simulated data. The
      model shows that transmission occurs in two different regimes, depending on the
      parameters of the particular problem. In the first regime, the cone alters the
      spatial phase distribution of the incident field along the receiver's aperture,
      whereas its amplitude remains almost unchanged. Because the receiver integrates
      the field over the aperture, the phasing affects the measurements via
      constructive and destructive interference. In the second regime, the phase
      alteration is accompanied by large amplitude variations around an average value
      that is significantly smaller than the amplitude observed in the first regime.
      The approximation will aid the design of ultrasound tomography arrays, such as
      those being developed for breast cancer detection.

PMID- 23143579
TI  - Bragg waveguide ultrasound detectors.
AB  - Polymer Bragg grating waveguides (BGWs) are demonstrated as ultrasound detectors.
      The device is fabricated by a direct electron beam lithography technique using an
      epoxy-based photoresist as the core material, with grating features fabricated on
      the side walls of the rib waveguide. The main motivation for this design is the
      linear geometry of the device, which can be used in a linear array, facilitating
      high-frequency ultrasound imaging. The fabricated BGW device has a cross
      sectional area of 1.5 * 1.5 MUm and the grating length is 500 MUm. The optical
      resonance spectrum is measured and compared with a theoretical model. The BGW
      device is experimentally demonstrated for the detection of ultrasound waves
      emitted by a 25-MHz transducer. Detection sensitivity depends on optimal grating
      design for a steep resonance. The extension of a single-element BGW device to a
      linear array using optical wavelength division multiplexing is presented. The
      results demonstrate the potential use of BGW devices in highly compact array of
      optoacoustic detectors for high-sensitivity ultrasound detection and
      photoacoustic imaging.

PMID- 23143580
TI  - Crosstalk reduction for high-frequency linear-array ultrasound transducers using
      1-3 piezocomposites with pseudo-random pillars.
AB  - The goal of this research was to develop a novel diced 1-3 piezocomposite
      geometry to reduce pulse-echo ring down and acoustic crosstalk between high
      frequency ultrasonic array elements. Two PZT-5H-based 1-3 composites (10 and 15
      MHz) of different pillar geometries [square (SQ), 45 degrees  triangle (TR), and
      pseudo-random (PR)] were fabricated and then made into single-element ultrasound
      transducers. The measured pulse-echo waveforms and their envelopes indicate that
      the PR composites had the shortest -20-dB pulse length and highest sensitivity
      among the composites evaluated. Using these composites, 15-MHz array subapertures
      with a 0.95lambda pitch were fabricated to assess the acoustic crosstalk between
      array elements. The combined electrical and acoustical crosstalk between the
      nearest array elements of the PR array subapertures (-31.8 dB at 15 MHz) was 6.5
      and 2.2 dB lower than those of the SQ and the TR array subapertures,
      respectively. These results demonstrate that the 1-3 piezocomposite with the
      pseudo-random pillars may be a better choice for fabricating enhanced high
      frequency linear-array ultrasound transducers; especially when mechanical dicing
      is used.

PMID- 23143581
TI  - Thin-film sparse boundary array design for passive acoustic mapping during
      ultrasound therapy.
AB  - A new 2-D hydrophone array for ultrasound therapy monitoring is presented, along
      with a novel algorithm for passive acoustic mapping using a sparse weighted
      aperture. The array is constructed using existing polyvinylidene fluoride (PVDF)
      ultrasound sensor technology, and is utilized for its broadband characteristics
      and its high receive sensitivity. For most 2-D arrays, high-resolution imagery is
      desired, which requires a large aperture at the cost of a large number of
      elements. The proposed array's geometry is sparse, with elements only on the
      boundary of the rectangular aperture. The missing information from the interior
      is filled in using linear imaging techniques. After receiving acoustic emissions
      during ultrasound therapy, this algorithm applies an apodization to the sparse
      aperture to limit side lobes and then reconstructs acoustic activity with high
      spatiotemporal resolution. Experiments show verification of the theoretical point
      spread function, and cavitation maps in agar phantoms correspond closely to
      predicted areas, showing the validity of the array and methodology.

PMID- 23143582
TI  - Calculation of the dispersive characteristics of acoustic waves in piezoelectric
      layered structures under the effect of DC electric field.
AB  - Relations used for calculation of the layered piezoelectric structures
      parameters, including the influence of the uniform dc electric field, have been
      obtained. Dispersive dependences and anisotropy of phase velocities,
      electromechanical coupling coefficients, power flow angle, and the influence of
      controlling coefficients of the dc electric field as a function of the h * f
      product for the Rayleigh and Love modes in bismuth germanium oxide/fused silica
      and langasite/fused silica layered structures have been calculated.

PMID- 23143583
TI  - Nondestructive testing ultrasonic immersion probe assessment and uncertainty
      evaluation according to EN 12668-2:2010.
AB  - Ultrasonic beam parameters from nondestructive testing probes and respective
      measurement uncertainties were calculated according to the Guide to the
      Expression of Uncertainty in Measurement (BIPM-JCGM-100:2008). The major
      conclusion of this work is that proper measurements of ultrasonic probes
      parameters are necessary because each probe has intrinsic construction
      particularities. Uncertainty evaluation was essential to properly assess the
      experimental results.

PMID- 23143584
TI  - Interaction of an acoustical quasi-Gaussian beam with a rigid sphere: linear
      axial scattering, instantaneous force, and time-averaged radiation force.
AB  - This work focuses on the interaction of an acoustical quasi-Gaussian beam
      centered on a rigid immovable sphere, during which at least three physical
      phenomena arise--the (axial) acoustic scattering, the instantaneous force, and
      the time-averaged radiation force--which are investigated here. The quasi
      Gaussian beam is an exact solution of the source-free Helmholtz wave equation and
      is characterized by an arbitrary waist, w(0), and a diffraction convergence
      length known as the Rayleigh range, z(R). Specialized formulations for the
      scattering and the instantaneous force function, as well as the (time-averaged)
      radiation force function, are provided. Numerical computations illustrate the
      variations of the backscattering form function, the instantaneous force function,
      and the (time-averaged) radiation force function versus the dimensionless
      frequency ka (where k is the wave number and a is the radius of the sphere); the
      results show significant differences from the plane wave limit when the
      dimensionless beam waist parameter kw(0) <25. The radiation force function may be
      used to calibrate high-frequency transducers operating with this type of beam.
      Furthermore, the theoretical analysis can be readily extended to the case of
      other types of spheres (i.e., elastic, viscoelastic, shells, and coated spheres
      and shells), providing that their appropriate scattering coefficients are used.

PMID- 23143585
TI  - Correction factors of the Mindlin plate equations with the consideration of
      electrodes.
AB  - The Mindlin plate theory plays a vital role in the analysis of high-frequency
      vibrations of quartz crystal resonators in the thickness-shear mode. The coupled
      equations with an infinite number of vibration modes have been truncated to
      retain essential modes with strong couplings for simplified analysis, and
      correction factors have been introduced to ensure exact solutions at cut-off
      frequencies as part of the validation procedure. Starting from plates without
      complications, correction factors have also been modified to include electrodes
      for their mass effect. Such results have been important for higher-order
      correction factors to ensure accurate consideration of electrodes in AT-cut
      quartz crystal plates. The findings in this systematic study of correction
      factors are readily available for the analytical equations with selected modes
      with strong couplings, and equally convenient for the implementation of the
      finite element analysis with the Mindlin plate equations.

PMID- 23143586
TI  - Laser detection of ultrasonic waves with concave portions of the wave fronts.
AB  - Special features of ultrasonic pulse wave field detection with concave regions of
      the wave fronts are investigated with the use of ultrasonic laser interferometry
      technique. Experimental proofs of the wave front with concave regions are
      obtained and it is found that the nonmonotonic wave front profiles are well
      described by the fourth-order even polynomial. The model proposed is applied to
      the investigation of the spatiotemporal structure of elastic wave fields on solid
      surfaces. The results obtained can be used for estimating the local wave front
      curvature.

PMID- 23143587
TI  - New acoustic plate modes with quasi-linear polarizations.
AB  - New acoustic plate modes (APMs) with quasishear- vertical (QSV) and quasi-shear
      horizontal (QSH) polarizations are found numerically in piezoelectric,
      nonpiezoelectric, and isotropic plates with free faces. Experimental verification
      of the modes is accomplished for ST,X-quartz plate, as an example. Similar to the
      modes with quasi-longitudinal displacement reported recently, the new
      counterparts exist when their velocities v(APM) are close to the velocities
      v(BAW) of the relevant bulk waves, the value of the dispersion slope
      dv(APM)/d(h/lambda) is low enough (dv(APM)/d(h/lambda) ~100 m/s, where h is
      thickness and lambda is wavelength), and allowable plate thickness h/lambda form
      a regular succession. All modes with quasi-linear polarization originate from
      generalized Lamb modes transformed at the aforementioned conditions.

PMID- 23143589
TI  - The validation of the Turkish version of Asthma Control Test.
AB  - INTRODUCTION: Current guidelines focus more on levels of asthma control than on
      severity of asthma. The original version of the Asthma Control Test (ACT), a self
      administered instrument to determine asthma control levels, was designed for
      English-speaking patients. More recently, the ACT has been translated into many
      languages and has been validated for many cultures, but this is the first study
      to evaluate the Turkish version. PURPOSE: We aimed to evaluate the reliability,
      validity, and responsiveness of the Turkish version of the ACT among outpatients
      with asthma. METHOD: This multicenter prospective study included 220 asthma
      patients in outpatient clinics in Turkey. The ACT was completed at admission
      (Visit 1), after 10 +/- 2 days (Visit 2), and at 5 +/- 1 weeks (Visit 3). At each
      visit, physicians assessed patients' asthma control levels. RESULTS: The Turkish
      version of the ACT showed an internal consistency reliability of 0.84 (Cronbach's
      alpha). Test-retest reliability was 0.85 in stable patients. There was a
      significant correlation between the ACT and physicians' assessments at admission
      (r = 0.68, p < 0.001). The AUC was 0.91, with a sensitivity of 89.06% and a
      specificity of 78.26% for a score of <=19 for screening "uncontrolled" asthma. A
      minimally important difference of three points on the ACT was consistent with the
      GINA physician assessment scores between the baseline and the follow-up visits.
      CONCLUSION: The Turkish version of the ACT is a valid and reliable tool for
      assessing asthma control in patients in outpatient settings. The test may
      facilitate the designation of asthma patients' symptoms as either controlled or
      uncontrolled.

PMID- 23143590
TI  - The effect of Tai Chi on health-related quality of life in people with elevated
      blood glucose or diabetes: a randomized controlled trial.
AB  - PURPOSE: The aim was to assess the effects of a Tai Chi-based program on health
      related quality of life (HR-QOL) in people with elevated blood glucose or
      diabetes who were not on medication for glucose control. METHOD: 41 participants
      were randomly allocated to either a Tai Chi intervention group (N = 20) or a
      usual medical-care control group (N = 21). The Tai Chi group involved 3 * 1.5 h
      supervised and group-based training sessions per week for 12 weeks. Indicators of
      HR-QOL were assessed by self-report survey immediately prior to and after the
      intervention. RESULTS: There were significant improvements in favor of the Tai
      Chi group for the SF36 subscales of physical functioning (mean difference = 5.46,
      95% CI = 1.35-9.57, P < 0.05), role physical (mean difference = 18.60, 95% CI =
      2.16-35.05, P < 0.05), bodily pain (mean difference = 9.88, 95% CI = 2.06-17.69,
      P < 0.05) and vitality (mean difference = 9.96, 95% CI = 0.77-19.15, P < 0.05).
      CONCLUSIONS: The findings show that this Tai Chi program improved indicators of
      HR-QOL including physical functioning, role physical, bodily pain and vitality in
      people with elevated blood glucose or diabetes who were not on diabetes
      medication.

PMID- 23143591
TI  - Conditional probability of survival nomogram for 1-, 2-, and 3-year survivors
      after an R0 resection for gastric cancer.
AB  - BACKGROUND: Survival estimates after curative surgery for gastric cancer are
      based on AJCC staging, or on more accurate multivariable nomograms. However, the
      risk of dying of gastric cancer is not constant over time, with most deaths
      occurring in the first 2 years after resection. Therefore, the prognosis for a
      patient who survives this critical period improves. This improvement over time is
      termed conditional probability of survival (CPS). Objectives of this study were
      to develop a CPS nomogram predicting 5-year disease-specific survival (DSS) from
      the day of surgery for patients surviving a specified period of time after a
      curative gastrectomy and to explore whether variables available with follow-up
      improve the nomogram in the follow-up setting. METHODS: A CPS nomogram was
      developed from a combined US-Dutch dataset, containing 1,642 patients who
      underwent an R0 resection with or without chemotherapy/radiotherapy for gastric
      cancer. Weight loss, performance status, hemoglobin, and albumin 1 year after
      resection were added to the baseline variables of this nomogram. RESULTS: The CPS
      nomogram was highly discriminating (concordance index: 0.772). Surviving 1, 2, or
      3 years gives a median improvement of 5-year DSS from surgery of 7.2, 19.1, and
      31.6 %, compared with the baseline prediction directly after surgery.
      Introduction of variables available at 1-year follow-up did not improve the
      nomogram. CONCLUSIONS: A robust gastric cancer nomogram was developed to predict
      survival for patients alive at time points after surgery. Introduction of
      additional variables available after 1 year of follow-up did not further improve
      this nomogram.

PMID- 23143592
TI  - Do MRI reports contain adequate preoperative staging information for end users to
      make appropriate treatment decisions for rectal cancer?
AB  - PURPOSE: This study was designed to elicit end-user opinions regarding the
      importance and diagnostic accuracy of MRI for T-category, threatened or involved
      circumferential margin (CRMi), and lymph node involvement (LNi) for preoperative
      staging of rectal cancer and to determine completeness of MRI reports for these
      elements on a population based level. METHODS: The first part of this study was a
      mailed survey of surgeons, radiation oncologists, and medical oncologists to
      elicit their opinions regarding the importance and diagnostic accuracy of T
      category, CRMi, and LNi on MRI. The second part of the study was an audit of MRI
      reports issued for pre-operative staging of rectal cancer to assess the
      completeness of these reports for T-category, CRMi, and LNi. RESULTS: Although T
      category, CRMi, and LNi were considered essential by 97, 94, and 77 % of
      respondents, respectively, the MRI report audit showed that only 40 % of MRI
      reports captured all of these elements. The majority of end users reported
      moderate diagnostic accuracy on MRI for T-category and CRMi and low diagnostic
      accuracy for LNi (52.3, 43, and 48.5 % respectively). Multivariate analysis
      showed that specialty was the only independent predictor of correct reporting of
      the diagnostic accuracy for each of the MRI elements. CONCLUSIONS: While end
      users consider T-category, CRMi and LNi essential for preoperative staging of
      rectal cancer, less than 40 % of MRI reports captured all of these elements.
      Therefore, strategies to improve communication between radiologists and end users
      are critical to improve the overall quality of care for rectal cancer patients.

PMID- 23143593
TI  - Longitudinal changes in function, symptom burden, and quality of life in patients
      with early-stage lung cancer.
AB  - BACKGROUND: Emerging evidence supports the integration of palliative care
      concurrently with disease-focused care in patients with serious illnesses, such
      as lung cancer. This paper describes how longitudinal changes in physical
      function, symptom burden, and QOL of patients with early-stage non-small cell
      lung cancer (NSCLC) informed the development of an interdisciplinary, tailored
      palliative care intervention. METHODS: Patients with early stage (I-IIIB) NSCLC
      were accrued into the usual care phase (Phase 1) of an NCI-funded Program Project
      Grant. Baseline and longitudinal (up to 52 weeks post-accrual) physical function,
      symptoms, and QOL were assessed in the thoracic ambulatory clinics of one NCI
      designated Comprehensive Cancer Center. Outcome measures included geriatric
      assessments, psychological distress, symptoms, and QOL. The association between
      disease stage (I-II vs. III) and longitudinal changes in these domains was
      evaluated. RESULTS: A total of 103 patients were accrued. Stage I-II patients
      were significantly more likely to complete the study (p = 0.005). The stages (I
      II vs. III) were equivalent at baseline on all demographic variables, clinical,
      and functional status. Physical function fluctuated longitudinally and was higher
      at 6 and 24 weeks than at baseline and 12 weeks. There was a longitudinal
      decrease in total number of symptoms (p < 0.001). Physical and social/family QOL
      fluctuated longitudinally (p < 0.001 and p = 0.016, respectively). CONCLUSIONS:
      Patients with early-stage NSCLC report a significant longitudinal decrease in
      physical QOL, and fluctuations in objective and subjective measures of physical
      function over time were observed regardless of disease stage category. An
      interdisciplinary palliative care intervention is currently being tested to
      decrease symptom burden and improve QOL.

PMID- 23143594
TI  - Identification of 15 new psoriasis susceptibility loci highlights the role of
      innate immunity.
AB  - To gain further insight into the genetic architecture of psoriasis, we conducted
      a meta-analysis of 3 genome-wide association studies (GWAS) and 2 independent
      data sets genotyped on the Immunochip, including 10,588 cases and 22,806
      controls. We identified 15 new susceptibility loci, increasing to 36 the number
      associated with psoriasis in European individuals. We also identified, using
      conditional analyses, five independent signals within previously known loci. The
      newly identified loci shared with other autoimmune diseases include candidate
      genes with roles in regulating T-cell function (such as RUNX3, TAGAP and STAT3).
      Notably, they included candidate genes whose products are involved in innate host
      defense, including interferon-mediated antiviral responses (DDX58), macrophage
      activation (ZC3H12C) and nuclear factor (NF)-kappaB signaling (CARD14 and CARM1).
      These results portend a better understanding of shared and distinctive genetic
      determinants of immune-mediated inflammatory disorders and emphasize the
      importance of the skin in innate and acquired host defense.

PMID- 23143595
TI  - Recurrent mutation of the ID3 gene in Burkitt lymphoma identified by integrated
      genome, exome and transcriptome sequencing.
AB  - Burkitt lymphoma is a mature aggressive B-cell lymphoma derived from germinal
      center B cells. Its cytogenetic hallmark is the Burkitt translocation
      t(8;14)(q24;q32) and its variants, which juxtapose the MYC oncogene with one of
      the three immunoglobulin loci. Consequently, MYC is deregulated, resulting in
      massive perturbation of gene expression. Nevertheless, MYC deregulation alone
      seems not to be sufficient to drive Burkitt lymphomagenesis. By whole-genome,
      whole-exome and transcriptome sequencing of four prototypical Burkitt lymphomas
      with immunoglobulin gene (IG)-MYC translocation, we identified seven recurrently
      mutated genes. One of these genes, ID3, mapped to a region of focal homozygous
      loss in Burkitt lymphoma. In an extended cohort, 36 of 53 molecularly defined
      Burkitt lymphomas (68%) carried potentially damaging mutations of ID3. These were
      strongly enriched at somatic hypermutation motifs. Only 6 of 47 other B-cell
      lymphomas with the IG-MYC translocation (13%) carried ID3 mutations. These
      findings suggest that cooperation between ID3 inactivation and IG-MYC
      translocation is a hallmark of Burkitt lymphomagenesis.

PMID- 23143597
TI  - The genetic landscape of mutations in Burkitt lymphoma.
AB  - Burkitt lymphoma is characterized by deregulation of MYC, but the contribution of
      other genetic mutations to the disease is largely unknown. Here, we describe the
      first completely sequenced genome from a Burkitt lymphoma tumor and germline DNA
      from the same affected individual. We further sequenced the exomes of 59 Burkitt
      lymphoma tumors and compared them to sequenced exomes from 94 diffuse large B
      cell lymphoma (DLBCL) tumors. We identified 70 genes that were recurrently
      mutated in Burkitt lymphomas, including ID3, GNA13, RET, PIK3R1 and the SWI/SNF
      genes ARID1A and SMARCA4. Our data implicate a number of genes in cancer for the
      first time, including CCT6B, SALL3, FTCD and PC. ID3 mutations occurred in 34% of
      Burkitt lymphomas and not in DLBCLs. We show experimentally that ID3 mutations
      promote cell cycle progression and proliferation. Our work thus elucidates
      commonly occurring gene-coding mutations in Burkitt lymphoma and implicates ID3
      as a new tumor suppressor gene.

PMID- 23143599
TI  - Vertebrate kidney tubules elongate using a planar cell polarity-dependent,
      rosette-based mechanism of convergent extension.
AB  - Cystic kidney diseases are a global public health burden, affecting over 12
      million people. Although much is known about the genetics of kidney development
      and disease, the cellular mechanisms driving normal kidney tubule elongation
      remain unclear. Here, we used in vivo imaging to show for the first time that
      mediolaterally oriented cell intercalation is fundamental to vertebrate kidney
      morphogenesis. Unexpectedly, we found that kidney tubule elongation is driven in
      large part by a myosin-dependent, multicellular rosette-based mechanism,
      previously only described in Drosophila melanogaster. In contrast to findings in
      Drosophila, however, non-canonical Wnt and planar cell polarity (PCP) signaling
      is required to control rosette topology and orientation during vertebrate kidney
      tubule elongation. These data resolve long-standing questions concerning the role
      of PCP signaling in the developing kidney and, moreover, establish rosette-based
      intercalation as a deeply conserved cellular engine for epithelial morphogenesis.

PMID- 23143598
TI  - Loss-of-function mutations in IGSF1 cause an X-linked syndrome of central
      hypothyroidism and testicular enlargement.
AB  - Congenital central hypothyroidism occurs either in isolation or in conjunction
      with other pituitary hormone deficits. Using exome and candidate gene sequencing,
      we identified 8 distinct mutations and 2 deletions in IGSF1 in males from 11
      unrelated families with central hypothyroidism, testicular enlargement and
      variably low prolactin concentrations. IGSF1 is a membrane glycoprotein that is
      highly expressed in the anterior pituitary gland, and the identified mutations
      impair its trafficking to the cell surface in heterologous cells. Igsf1-deficient
      male mice show diminished pituitary and serum thyroid-stimulating hormone (TSH)
      concentrations, reduced pituitary thyrotropin-releasing hormone (TRH) receptor
      expression, decreased triiodothyronine concentrations and increased body mass.
      Collectively, our observations delineate a new X-linked disorder in which loss-of
      function mutations in IGSF1 cause central hypothyroidism, likely secondary to an
      associated impairment in pituitary TRH signaling.

PMID- 23143600
TI  - Digenic inheritance of an SMCHD1 mutation and an FSHD-permissive D4Z4 allele
      causes facioscapulohumeral muscular dystrophy type 2.
AB  - Facioscapulohumeral dystrophy (FSHD) is characterized by chromatin relaxation of
      the D4Z4 macrosatellite array on chromosome 4 and expression of the D4Z4-encoded
      DUX4 gene in skeletal muscle. The more common form, autosomal dominant FSHD1, is
      caused by contraction of the D4Z4 array, whereas the genetic determinants and
      inheritance of D4Z4 array contraction-independent FSHD2 are unclear. Here, we
      show that mutations in SMCHD1 (encoding structural maintenance of chromosomes
      flexible hinge domain containing 1) on chromosome 18 reduce SMCHD1 protein levels
      and segregate with genome-wide D4Z4 CpG hypomethylation in human kindreds. FSHD2
      occurs in individuals who inherited both the SMCHD1 mutation and a normal-sized
      D4Z4 array on a chromosome 4 haplotype permissive for DUX4 expression. Reducing
      SMCHD1 levels in skeletal muscle results in D4Z4 contraction-independent DUX4
      expression. Our study identifies SMCHD1 as an epigenetic modifier of the D4Z4
      metastable epiallele and as a causal genetic determinant of FSHD2 and possibly
      other human diseases subject to epigenetic regulation.

PMID- 23143596
TI  - High-density genetic mapping identifies new susceptibility loci for rheumatoid
      arthritis.
AB  - Using the Immunochip custom SNP array, which was designed for dense genotyping of
      186 loci identified through genome-wide association studies (GWAS), we analyzed
      11,475 individuals with rheumatoid arthritis (cases) of European ancestry and
      15,870 controls for 129,464 markers. We combined these data in a meta-analysis
      with GWAS data from additional independent cases (n = 2,363) and controls (n =
      17,872). We identified 14 new susceptibility loci, 9 of which were associated
      with rheumatoid arthritis overall and five of which were specifically associated
      with disease that was positive for anticitrullinated peptide antibodies, bringing
      the number of confirmed rheumatoid arthritis risk loci in individuals of European
      ancestry to 46. We refined the peak of association to a single gene for 19 loci,
      identified secondary independent effects at 6 loci and identified association to
      low-frequency variants at 4 loci. Bioinformatic analyses generated strong
      hypotheses for the causal SNP at seven loci. This study illustrates the
      advantages of dense SNP mapping analysis to inform subsequent functional
      investigations.

PMID- 23143601
TI  - Genome-wide association analysis identifies new lung cancer susceptibility loci
      in never-smoking women in Asia.
AB  - To identify common genetic variants that contribute to lung cancer
      susceptibility, we conducted a multistage genome-wide association study of lung
      cancer in Asian women who never smoked. We scanned 5,510 never-smoking female
      lung cancer cases and 4,544 controls drawn from 14 studies from mainland China,
      South Korea, Japan, Singapore, Taiwan and Hong Kong. We genotyped the most
      promising variants (associated at P < 5 * 10(-6)) in an additional 1,099 cases
      and 2,913 controls. We identified three new susceptibility loci at 10q25.2
      (rs7086803, P = 3.54 * 10(-18)), 6q22.2 (rs9387478, P = 4.14 * 10(-10)) and
      6p21.32 (rs2395185, P = 9.51 * 10(-9)). We also confirmed associations reported
      for loci at 5p15.33 and 3q28 and a recently reported finding at 17q24.3. We
      observed no evidence of association for lung cancer at 15q25 in never-smoking
      women in Asia, providing strong evidence that this locus is not associated with
      lung cancer independent of smoking.

PMID- 23143604
TI  - Self-etching aspects of a three-step etch-and-rinse adhesive.
AB  - PURPOSE: The purpose of this study is to assess the marginal adaptation of
      cavities restored with a three-step etch-and-rinse adhesive, OptiBond FL (OFL)
      under different application protocols. MATERIALS AND METHODS: Twenty-four class V
      cavities were prepared with half of the margins located in enamel and half in
      dentin. Cavities were restored with OFL and a microhybrid resin composite
      (Clearfil AP-X). Three groups (n = 8) that differed in the etching technique were
      tested with thermomechanical loading, and specimens were subjected to
      quantitative marginal analysis before and after loading. Micromorphology of
      etching patters on enamel and dentin were observed with SEM. Data was evaluated
      with Kruskal-Wallis and Bonferroni post hoc test. RESULTS: Significantly lower
      percent CM (46.9 +/- 19.5) were found after loading on enamel in group 3 compared
      to group 1 (96.5 +/- 5.1) and group 2 (93.1 +/- 8.1). However, no significant
      differences (p = 0.30) were observed on dentin margins. CONCLUSIONS: Etching
      enamel with phosphoric acid but avoiding etching dentin before the application of
      OFL, optimal marginal adaptation could be obtained, evidencing a self-etching
      primer effect. CLINICAL RELEVANCE: A reliable adhesive interface was attained
      with the application of the three-step etch-and-rinse OFL adhesive with a
      selective enamel etching, representing an advantage on restoring deep cavities.

PMID- 23143603
TI  - Synchronization of the flowering transition by the tomato TERMINATING FLOWER
      gene.
AB  - The transition to flowering is a major determinant of plant architecture, and
      variation in the timing of flowering can have profound effects on inflorescence
      architecture, flower production and yield. Here, we show that the tomato mutant
      terminating flower (tmf) flowers early and converts the multiflowered
      inflorescence into a solitary flower as a result of precocious activation of a
      conserved floral specification complex encoded by ANANTHA (AN) and FALSIFLORA
      (FA). Without TMF, the coordinated flowering process is disrupted, causing floral
      identity genes, such as AN and members of the SEPALLATA (SEP) family, to activate
      precociously, while the expression of flowering transition genes, such as
      FRUITFULL (FUL), is delayed. Indeed, driving AN expression precociously is
      sufficient to cause early flowering, and this expression transforms multiflowered
      inflorescences into normal solitary flowers resembling those of the Solanaceae
      species petunia and tobacco. Thus, by timing AN activation, TMF synchronizes
      flower formation with the gradual reproductive transition, which, in turn, has a
      key role in determining simple versus complex inflorescences.

PMID- 23143605
TI  - Giant cell tumor of the tendon sheath mimicking a primary intramedullary
      metatarsal tumor.
AB  - Giant cell tumor of the tendon sheath (GCTTS) is one of the most common benign
      soft tissue tumors in the extremities, and is frequently associated with bone
      abnormalities. Although extrinsic bone erosion is the most common bone
      abnormality associated with GCTTS, intraosseous invasion of GCTTS occurs rarely
      and may mimic a primary bone tumor, making diagnosis more challenging. We report
      an unusual imaging presentation of GCTTS mimicking a primary intramedullary
      metatarsal tumor and review the literature on the frequency of bone involvement
      of GCTTS.

PMID- 23143602
TI  - Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol
      related and sporadic pancreatitis.
AB  - Pancreatitis is a complex, progressively destructive inflammatory disorder.
      Alcohol was long thought to be the primary causative agent, but genetic
      contributions have been of interest since the discovery that rare PRSS1, CFTR and
      SPINK1 variants were associated with pancreatitis risk. We now report two
      associations at genome-wide significance identified and replicated at PRSS1-PRSS2
      (P < 1 * 10(-12)) and X-linked CLDN2 (P < 1 * 10(-21)) through a two-stage genome
      wide study (stage 1: 676 cases and 4,507 controls; stage 2: 910 cases and 4,170
      controls). The PRSS1 variant likely affects disease susceptibility by altering
      expression of the primary trypsinogen gene. The CLDN2 risk allele is associated
      with atypical localization of claudin-2 in pancreatic acinar cells. The
      homozygous (or hemizygous in males) CLDN2 genotype confers the greatest risk, and
      its alleles interact with alcohol consumption to amplify risk. These results
      could partially explain the high frequency of alcohol-related pancreatitis in men
      (male hemizygote frequency is 0.26, whereas female homozygote frequency is 0.07).

PMID- 23143606
TI  - Role of pharmacogenetics on adjuvant chemotherapy-induced neutropenia in Chinese
      breast cancer patients.
AB  - BACKGROUND: Breast cancer patients regularly undergo adjuvant chemotherapies
      following surgery. However, these treatments are largely associated with
      chemotherapeutic toxicities ranging from nausea to severe myelosuppression. In
      this investigation, we examined the effects of four SNPs in NR1I2, CYP3A4 and
      CYP3A5 genes on chemotherapy-induced severe neutropenia in 311 female Chinese
      breast cancer patients undergoing a standard adjuvant chemotherapy regimen.
      METHODS: Patients were monitored for adverse reactions throughout the treatment,
      then divided into "none or mild" (80 %) or "severe" (20 %) toxicity groups
      according to whether they suffered grade 4 neutropenia defined as having an
      absolute neutrophil counts (ANC) of less than 0.5 * 10(9)/L anytime during the
      treatment. DNA was extracted from patients' peripheral blood samples, then
      genotyped using allele-specific Tm-shift PCR and melting analysis. RESULTS:
      Logistic regression revealed that rs776746 or CYP3A5*3 strongly associated with
      grade 4 neutropenia (OR = 2.56, P = 0.023) after adjustment for covariates, one
      of which more significant factor was baseline ANC (OR = 0.68, P = 0.020).
      Although univariate analysis in all patients did not reveal any association at
      first, further analysis indicated that rs776746 is significantly associated with
      severe neutropenia in subgroup of breast cancer patients with normal baseline ANC
      (>=2.0 * 10(9)/L). These carriers of A-allele have 3.14-fold increased risk of
      developing severe neutropenia (P = 0.004). CONCLUSION: Our results suggested that
      polymorphisms in CYP3A5 might be useful pharmacogenetic markers for the
      prediction of severe neutropenia during chemotherapy, however, only after
      screening patients by their baseline ANC in the presence of gene-environmental
      interaction. We demonstrate an approach of pharmacogenetic analysis, in which the
      genetic data should be analyzed in the perspective of other clinical parameters.

PMID- 23143607
TI  - Cardiovascular and behavioral response to auditory stimuli in boys with fragile X
      syndrome.
AB  - OBJECTIVE: The aim of this study was to determine whether young boys with fragile
      X syndrome (FXS) exhibit abnormal physiological or behavioral responses to a
      moderately intense auditory stimulus, as heightened sensory reactivity is
      believed to contribute to problem behaviors in this population. METHODS: We
      examined the physiological basis, via heart activity, of auditory startle in
      young boys with FXS (n = 22) compared with typically developing controls (n =
      27). Associations with mental age, behavioral reactivity, and chronological age
      were examined. RESULTS: Results suggest that older boys with FXS display
      increased cardiac reactivity to auditory input than younger boys with FXS that
      distinguishes them from typically developing controls. Higher mental age was
      associated with decreased latency to react. CONCLUSIONS: Results contribute to
      increased understanding of the pathology in sensory processing in boys with FXS,
      which can inform refinement of the phenotype in young children with FXS and aid
      in the development of efficacious psychopharmacological and/or behavioral
      interventions.

PMID- 23143608
TI  - Toddlers' unintentional injuries: the role of maternal-reported paternal and
      maternal supervision.
AB  - Research indicates that mothers' supervision protects children from injuries.
      However, little research has examined the role of fathers' supervision in
      children's injuries. OBJECTIVES: This study compared the role of maternal and
      paternal supervision in children's injury risk and severity using maternal
      reports. METHODS: Mothers (n = 170) of toddlers were interviewed for 6 months
      about their children's unintentional injuries. RESULTS: Children were more likely
      to engage in high activity levels and were at higher risk for injury when being
      cared for by their fathers. Although higher supervision predicted lower injury
      risk for both mothers and fathers, fathers' close supervision (as reported by
      mothers) was a stronger predictor of injury risk than mothers' supervision.
      CONCLUSION: Children's higher levels of activities may have accounted for their
      higher risk of injury when in their fathers' care. These findings indicate the
      need to include fathers in injury prevention efforts.

PMID- 23143609
TI  - Synthesis, characterization, and electrochemical properties of diiron
      propaneditellurolate (PDTe) complexes as active site models of [FeFe]
      hydrogenases.
AB  - Parent complex (MU-PDTe)Fe(2)(CO)(6) (1, PDTe = MU-TeCH(2)CH(2)CH(2)Te-MU) is
      prepared via a new synthetic route involving the reaction of (MU
      Te(2))Fe(2)(CO)(6) with Et(3)BHLi, followed by treatment of (MU
      LiTe)(2)Fe(2)(CO)(6) with Br(CH(2))(3)Br in a 43% yield. Further reactions of 1
      with 1 equiv of monophosphines in the presence of the decarbonylating agent
      Me(3)NO afford the corresponding monophosphine-substituted complexes (MU
      PDTe)Fe(2)(CO)(5)(L) (2, L = PPh(3); 3, PPh(2)H; 4, PMe(3)) in 37%-47% yields,
      whereas the N-heterocyclic carbene I(Mes)-monosubstituted complex (MU
      PDTe)Fe(2)(CO)(5)(I(Mes)) (5) can be prepared in a 26% yield by treatment of 1
      with the in situ generated I(Mes) from the 1,3-bis(mesityl)imidazolium salt
      I(Mes).HCl and n-BuLi. While the diphosphine-bridged single-butterfly complexes
      (MU-PDTe)Fe(2)(CO)(4)(dppm) (6) and (MU-PDTe)Fe(2)(CO)(4)(dppn) (7) can be
      prepared in 28% and 21% yields by treatment of 1 with 1 equiv of the
      corresponding diphosphines in refluxing xylene, treatment of 1 with 0.5 equiv of
      diphosphines in the presence of Me(3)NO results in the formation of the
      corresponding diphosphine-bridged double-butterfly complexes [(MU
      PDTe)Fe(2)(CO)(5)](2)(dppp) (8), [(MU-PDTe)Fe(2)(CO)(5)](2)(dppb) (9), and [(MU
      PDTe)Fe(2)(CO)(5)](2)(dppf) (10) in 25-37% yields. All the new substituted model
      complexes 2-10 are characterized by combustion analysis and spectroscopy, and
      particularly for 2, 3, 5, and 7-10, by X-ray crystallography. In addition, a
      comparative study on the electrochemical and electrocatalytic properties of the
      PDTe-type model complexes 1 and 7 with their corresponding selenium and sulfur
      analogs are reported.

PMID- 23143610
TI  - Cohort profile: Steps to the healthy development and well-being of children (the
      STEPS Study).
AB  - The STEPS Study aims to search for the precursors and causes of problems in child
      health and well-being by using a multidisciplinary approach. The cohort consists
      of all mothers (Finnish or Swedish speaking) who had live deliveries in the
      Hospital District of Southwest Finland from January 2008 to April 2010 and their
      children (n=9811 mothers, n=9936 children). Of these, 1797 mothers and their 1827
      children were recruited to an intensive follow-up group during the first
      trimester of pregnancy or soon after delivery. Information about the whole study
      cohort is based on pregnancy follow-up data from maternity clinics, National
      Longitudinal Census Files and child welfare clinics. Data from multiple sources
      are used to obtain a picture of the overall well-being of the child and the
      family. After birth, study visits include several clinical examinations.
      Collaboration is encouraged, and access to the data will be available when the
      data set is complete.

PMID- 23143611
TI  - Cohort profile: the English longitudinal study of ageing.
AB  - The English Longitudinal Study of Ageing (ELSA) is a panel study of a
      representative cohort of men and women living in England aged >=50 years. It was
      designed as a sister study to the Health and Retirement Study in the USA and is
      multidisciplinary in orientation, involving the collection of economic, social,
      psychological, cognitive, health, biological and genetic data. The study
      commenced in 2002, and the sample has been followed up every 2 years. Data are
      collected using computer-assisted personal interviews and self-completion
      questionnaires, with additional nurse visits for the assessment of biomarkers
      every 4 years. The original sample consisted of 11 391 members ranging in age
      from 50 to 100 years. ELSA is harmonized with ageing studies in other countries
      to facilitate international comparisons, and is linked to financial and health
      registry data. The data set is openly available to researchers and analysts soon
      after collection (http://www.esds.ac.uk/longitudinal/access/elsa/l5050.asp). 

PMID- 23143613
TI  - Opioid-induced hyperalgesia and burn pain.
AB  - The treatment of pain produced during the management of burn injury has been an
      ongoing problem for physicians caring for these patients. The main therapeutic
      option for analgesia has been the repeated and prolonged use of opioids. The
      adverse effects of opioids are well known but the long term use of opioids which
      produces tolerance with accompanying dose escalation and dependence is most
      problematic. Another potentially important consequence of opioid exposure that
      sometimes masks as tolerance is that of opioid induced hyperalgesia. This
      syndrome is manifest as enhanced pain, sensitivity and loss of analgesic efficacy
      in patients treated with opioids who actually become sensitized to painful
      stimuli. This article focuses on the treatment of burn pain and how current
      analgesic therapies with opioids may cause hyperalgesia and affect the adequacy
      of treatment for burn pain. This article also provides possible modalities to
      help therapeutically manage these patients and considers future analgesic
      strategies which may help to improve pain management in this complicated patient
      population.

PMID- 23143614
TI  - A review of the use of human albumin in burn patients.
AB  - This review article examines the use of human albumin (HA) in burn treatment.
      Generally, there are two scenarios where HA may be administered: acutely as a
      volume expander during burn shock resuscitation and chronically following
      resuscitation to correct hypoalbuminemia. Although colloids were the cornerstone
      of the earliest burn resuscitation formulas, HA was in fact rarely used. More
      recently however, with the recognition of fluid creep, HA usage during
      resuscitation has increased. Animal studies demonstrate that during acute fluid
      resuscitation, administration of colloids, including albumin (ALB), have no
      ability to arrest the formation of burn wound edema, but they do reduce edema
      formation in the nonburn soft tissues and help preserve intravascular volume and
      reduce resuscitation fluid requirements with no apparent increase in
      extravascular water accumulation in the lung. Human studies suggest that
      immediate use of ALB during acute resuscitation achieves adequate resuscitation
      using a lower total overall volume requirement, transiently provides better
      maintenance of intravascular volume and cardiac output, produces less overall
      edema gain than crystalloid resuscitation alone but may be associated with
      increased extravascular lung water accumulation during the first postburn week.
      However, many questions remain unanswered, and modern, large-scale prospective
      studies are desperately needed. Maintenance of normal serum ALB levels through
      continuous supplementation of HA following burn resuscitation is even less well
      understood. Although this approach makes physiologic sense, the limited amount of
      available data from human burn studies reveal that chronic ALB supplementation is
      expensive and may not result in any major clinical benefits. Again, modernized
      prospective studies are greatly needed in this area.

PMID- 23143615
TI  - Combination of radiation and burn injury alters [18F] 2-fluoro-2-deoxy-D-glucose
      uptake in mice.
AB  - Radiation exposure and burn injury have both been shown to alter glucose
      utilization in vivo. The present study was designed to study the effect of burn
      injury combined with radiation exposure on glucose metabolism in mice using [18F]
      2-fluoro-2-deoxy-D-glucose (18FDG). Groups of male mice weighing approximately 30
      g were studied. Group 1 was irradiated with a 137Cs source (9 Gy). Group 2
      received full thickness burn injury on 25% TBSA followed by resuscitation with
      saline (2 ml, IP). Group 3 received radiation followed 10 minutes later by burn
      injury. Group 4 were sham-treated controls. After treatment, the mice were fasted
      for 23 hours and then injected (IV) with 50 MUCi of 18FDG. One hour
      postinjection, the mice were sacrificed, and biodistribution was measured.
      Positive blood cultures were observed in all groups of animals compared to the
      shams. Increased mortality was observed after 6 days in the burn plus radiated
      group as compared to the other groups. Radiation and burn treatments separately
      or in combination produced major changes in 18FDG uptake by many tissues. In the
      heart, brown adipose tissue, and spleen, radiation plus burn produced a much
      greater increase (P < .0001) in 18FDG accumulation than either treatment
      separately. All three treatments produced moderate decreases in 18FDG
      accumulation (P < .01) in the brain and gonads. Burn injury, but not irradiation,
      increased 18FDG accumulation in skeletal muscle; however, the combination of burn
      plus radiation decreased 18FDG accumulation in skeletal muscle. This model may be
      useful for understanding the effects of burns plus irradiation injury on glucose
      metabolism and in developing treatments for victims of injuries produced by the
      combination of burn plus irradiation.

PMID- 23143616
TI  - Psychometric properties of the Swedish version of the burn outcomes questionnaire
      for children aged 5 to 18 years.
AB  - Although pediatric burn injuries are common, there is a lack of burn-specific
      health outcome measurements for children. The American Burn Association and the
      Shriners Hospitals for Children have developed the Burn Outcomes Questionnaire
      (BOQ), which is a parent-report questionnaire measuring the functional outcome
      after burn in children aged 5 to 18 years. The aim of this study was to examine
      the psychometric properties of the Swedish version of the BOQ, assessing
      feasibility, reliability, and validity aspects. Participants were parents (n =
      70) of children aged 5 to 18 years who were treated at the Uppsala or Linkoping
      burn center between January 2000 and December 2008. For most subscales,
      feasibility was adequate and the internal consistency was good: Cronbach's alpha
      values were above 0.76 in all but 1 subscale, and mean interitem correlations
      ranged from 0.34 to 0.90. The test-retest reliability was significant in the
      majority of subscales. Evidence of validity was shown by associations among the
      BOQ subscales and between BOQ subscales and measures of burn severity, heat
      sensitivity, fear-avoidance beliefs, and parent reports of the child's
      psychological problems. In conclusion, with the exception of a few subscales,
      this study supports the continued evaluation of the Swedish version of BOQ as a
      tool to measure outcome after burn in children aged 5 to 18 years.

PMID- 23143617
TI  - Burns or phytophotodermatitis, abuse or neglect:  confusing aspects of skin
      lesions caused by the superstitious use of fig leaves.
AB  - As a superstition, homemade decoctions are believed to be beneficial for several
      diseases. This kind of medical therapy, however, can lead to serious adverse
      effects. In this report, we present three cases from a single family. Each of the
      family members developed phytophotodermatitis after the application of a fig leaf
      decoction. The most severe effect was in the case of a 13-year-old boy who had
      been bathed with the fig leaf decoction; the two other cases were the parents who
      prepared and applied the medicine to their child's skin to heal the boy's
      congenital mental-motor retardation. Silver sulfadiazine was used for wound care.
      The mother was discharged 6 days after admission, the father, after 8 days, and
      the boy, after 14 days. Burnlike wounds in all three cases healed completely.

PMID- 23143618
TI  - Hand injury caused by pressured powder gas.

PMID- 23143619
TI  - Multi-cell type human liver microtissues for hepatotoxicity testing.
AB  - Current 2-dimensional hepatic model systems often fail to predict chemically
      induced hepatotoxicity due to the loss of a hepatocyte-specific phenotype in
      culture. For more predictive in vitro models, hepatocytes have to be maintained
      in a 3-dimensional environment that allows for polarization and cell-cell
      contacts. Preferably, the model will reflect an in vivo-like multi-cell type
      environment necessary for liver-like responses. Here, we report the
      characterization of a multi-cell type microtissue model, generated from primary
      human hepatocytes and liver-derived non-parenchymal cells. Liver microtissues
      were stable and functional for 5 weeks in culture enabling, for example, long
      term toxicity testing of acetaminophen and diclofenac. In addition, Kupffer cells
      were responsive to inflammatory stimuli such as LPS demonstrating the possibility
      to detect inflammation-mediated toxicity as exemplified by the drug
      trovafloxacin. Herewith, we present a novel 3D liver model for routine testing in
      96-well format capable of reducing the risk of unwanted toxic effects in the
      clinic.

PMID- 23143620
TI  - Induction of skin sensitization is augmented in Nrf2-deficient mice.
AB  - Several in vitro DNA microarray studies have shown the importance of nuclear
      factor (erythroid-derived 2)-like 2 (Nrf2) in skin sensitization. Nevertheless,
      the exact in vivo role of the Nrf2-Keap1 pathway during the induction of skin
      sensitization remains unknown. To study the function of Nrf2, a local lymph node
      assay was performed in wild-type and Nrf2-deficient mice using 2,4
      dinitrochlorobenzene. The Nrf2-deficient mice show a more pronounced response,
      indicating that Nrf2 is involved in dampening the induction of skin
      sensitization.

PMID- 23143621
TI  - Thalidomide reduces recurrence of ankylosing spondylitis in patients following
      discontinuation of etanercept.
AB  - A previous study showed that most ankylosing spondylitis (AS) patients presented
      recurrence within 6 months post-discontinuation of etanercept. How to reduce
      recurrence following discontinuation of etanercept should be further researched.
      In this study, 111 ankylosing spondylitis patients meeting the Assessment in AS
      20 % response (ASAS20) criteria after 12-week administration of etanercept were
      randomized into three groups: Group I, 150 mg thalidomide once/day; Group II, 1 g
      sulfasalazine, twice/day; Group III, NSAIDs for the maintenance treatment. The
      patients were regularly followed up once a month, and AS recurrence was evaluated
      with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath
      Ankylosing Spondylitis Functional Index (BASFI), the patient global assessment
      (PGA), and rachialgia. The follow-up lasted for 1 year, and AS recurrence was
      considered as the end of a visit. Finally, 100 patients completed the follow-up
      study, of whom 30 were in Group I, 33 in Group II, and 37 in Group III. The
      average follow-up period was 5.1 +/- 3.9 months and the longest lasted for 12
      months. At the end of the follow-up study, the recurrence rates in Groups I, II,
      and III were, respectively, 60.0 % (18/30), 84.8 % (28/33), and 89.2 % (33/37).
      The recurrence rates of Group I were statistically significantly lower than that
      of Group II and III (P = 0.0265; P = 0.0053), while there was no significant
      difference between Group II and Group III. In addition, we found that PGA, C
      reactive protein (CRP), and spinal inflammation could be regarded as predictive
      factors for AS recurrence by analysis with the Cox proportional hazard model.
      This study points to a new way for maintenance therapy of AS following
      discontinuation of etanercept and reveals several useful indicators for
      prediction of AS recurrence.

PMID- 23143622
TI  - Study of hepatitis B prevalence in parallel with the most frequent HBV genotype
      in South Iranian blood donors.
AB  - BACKGROUND: Hepatitis B virus (HBV) is one of the leading causes of acute and
      chronic liver diseases and in turn responsible for a million of worldwide annual
      deaths. HBV has been classified into eight main groups, designated as A-H with
      different geographical distribution. Some genotypes are associated with different
      clinical outcomes and particular viral mutations. Current study was aimed to
      investigate the genotype and prevalence of HBV in blood donors of south of Iran.
      METHODS: This experimental study investigated the prevalence of HBV positivity in
      198,289 Iranian blood donors from south of Iran by both ELISA- and PCR-based
      methods. Within 198,289 donors, 120 HBsAg(+) cases were selected, HBV-DNA was
      extracted, and the p gene sequences were amplified by nested-PCR. The HBV
      genotypes were determined by direct sequencing of the polymerase gene of HBV.
      Phylogenetic trees also were constructed by the neighbor-joining (NJ) method.
      RESULTS: Findings of this study indicated that 0.184%, 0.329%, and 0.215% of
      blood donors were HBsAg(+) among Isfahan, Kerman, and Yazd provinces,
      respectively. Only 69 (57.5%) cases of 120 HBsAg(+) donors were HBV-DNA(+) .
      Sequencing analysis revealed that all of HBV-infected donors had the D genotype
      of HBV. CONCLUSIONS: In conclusion, the prevalence of genotype D was 100% in
      Iranian HBV blood donors. These findings may have an impact on the immunological
      and genetic diagnosis of HBV, selection of diagnostic kits, and viral quality
      control panels to evaluate diagnostic methods.

PMID- 23143623
TI  - Comparison of the Bactec Fx Plus, Mycosis IC/F, Mycosis/F Lytic blood culture
      media and the BacT/Alert 3D FA media for detection of Candida species in seeded
      blood culture specimens containing therapeutic peak levels of fluconazole.
AB  - BACKGROUND: The performance of Bactec Fx Plus Aerobic/F (PA), Mycosis IC/F (MF),
      Myco/F Lytic (ML) media and BacT/Alert 3D FA (FA) media in detecting 15 Candida
      isolates in blood cultures to which fluconazole had been added was investigated.
      METHODS: PA with resin, MF, ML media (n = 360), and FAmedia (n = 120) were tested
      against Candida albicans, C. tropicalis, C. parapsilosis, and C. krusei. As the
      peak plasma concentration after single oral doses of fluconazole 100, 200, and
      400 mg was equivalent to peak level of 1.9, 4.7, and 6.7 mg/l, respectively,
      corresponding fluconazole was added. Time to detection (TTD) was measured.
      RESULTS: Overall TTD (mean hour +/- standard deviation) for PA, FA, MF, and ML
      was as follows: 24.5 +/- 7.3, 27.0 +/- 7.5, 31.9 +/- 21.3, and 37.7 +/- 30.1,
      respectively. TTD of PA was shorter compared to other media. The effect of
      fluconazole was limited in PA and FA, but MF and ML showed delayed TTD. Larger
      inoculum size showed shorter TTDin PA and FA. CONCLUSION: TTD of Bactec Fx Plus
      Aerobic/F was more than 2.5 hr faster among the tested media. As thus system and
      media are unaffected by added fluconazole, it could be used for the diagnosis of
      candidemia in the clinical settings including the patients who have been treated
      empirically with fluconazole at the time when blood cultures were drawn.

PMID- 23143624
TI  - Porcine pancreas: a superior source of cholesterol esterase for total serum
      cholesterol assay by the enzymatic kinetic method.
AB  - BACKGROUND: Accurate determination of cholesterol requires complete hydrolysis of
      cholesteryl esters and must be very fast for the kinetic cholesterol assay. We
      investigated the properties of cholesterol esterase derived from Pseudomonas
      fluorescens, Candida cylindracea, bovine pancreas, and porcine pancreas for
      cholesterol determination in human serum. METHODS: Optimization of four enzymes
      and effect of sodium cholate concentration were performed. We evaluated and
      compared their performances in enzymatic kinetic cholesterol determination.
      RESULTS: The optimal sodium cholate concentration was 3, 5, 15, and 12 mmol/l
      with the enzyme activities at 200, 100, 100, and 100 U/l for P. fluorescens, C.
      cylindracea, bovine pancreas, and porcine pancreas, respectively. Linearity
      obtained from all enzymes was up to 16.3 mmol/l. All assays were compared
      favorably with standardized endpoint method. Only the cholesterol esterase
      derived from porcine pancreas demonstrated acceptable precision within the
      acceptable criteria (%CV < 3.0). Also, this esterase was least affected by
      interfering substances and showed longer stability than that of C. cylindracea
      and bovine pancreas. CONCLUSION: Porcine pancreas cholesterol esterase is
      superior to that obtained from P. fluorescens, C. cylindracea, and bovine
      pancreas for total serum cholesterol determination by the kinetic method because
      of its lower cost, better accuracy and precision, less interference, and longer
      stability.

PMID- 23143625
TI  - Flow cytometry immunophenotyping evaluation in acute lymphoblastic leukemia:
      correlation to factors affecting clinic outcome.
AB  - The authors conducted a flow cytometry immunophenotyping study in patients with
      acute lymphoblastic leukemia (ALL) from Natal, Rio Grande do Norte, Brazil. The
      patients (n = 126) were newly diagnosed using a panel of monoclonal antibodies:
      CD1a, CD2, CD3, CD4, CD7, CD8, CD10, CD13, CD33, CD14, CD19, CD22, CD79a, CD117,
      CD34, anti-IgM, anti-TdT, anti-HLA-Dr, and anti-human kappa and lambda light
      chains. Additional data, such as patients' age and gender, clinical and
      laboratory findings such as presence of tumor masses, lymphadenopathy,
      hepatomegaly, splenomegaly, leukemic infiltration in the central nervous system
      (CNS) were also investigated. Results showed that 56.7% of the cases were B
      lineage ALL and 55% were T-cell ALL. Also, we found that males were more affected
      by the disease, regardless of immunological classification. The correlation
      between age and immunological subtypes showed that the B-lineage ALL occurred
      more frequently in patients aged under 15 while the T-cell ALL subtype was more
      frequent in adults. Immunophenotypic profiles and morphological subtypes showed a
      direct correlation between L3 subtype and B-lineage ALL, while L1 and L2 subtypes
      correlated more often with B-cell lineage and T-cell ALL, respectively.
      Correlation analysis between immunophenotypic and clinical profiles showed that T
      cell ALL was more associated with a higher incidence of lymphadenopathy,
      hepatomegaly, splenomegaly and CNS leukemic infiltration, also showing a greater
      blast cell count in peripheral blood than the other subgroups. The presented data
      suggest that immunophenotyping is an important method in the diagnosis,
      monitoring and prognostic assessment in determining the pathological mechanisms
      of evolution of ALL.

PMID- 23143626
TI  - Hsa-miR-196a2 functional SNP is associated with severe toxicity after platinum
      based chemotherapy of advanced nonsmall cell lung cancer patients in a Chinese
      population.
AB  - BACKGROUND: Rs11614913 is a polymorphism in hsa-miR-196a2 reported to alter
      mature microRNA expression and function. This single-nucleotide polymorphism
      (SNP) was reported to be associated with susceptibility and prognosis of lung
      cancer. METHODS: In this article, association study was performed to reveal the
      relation between SNP and response rate or severe toxicity after platinum-based
      regimen in advanced nonsmall cell lung cancer patients. RESULTS: By screening
      this polymorphism in 442 Chinese patients with MALDI-TOF Mass Spectrometer,
      significantly higher occurrence of grade 3 or 4 overall toxicity (P = 0.02) in
      response to treatment was found in patients with homozygous CC. After stratified
      analyses, association between rs11614912 and overall toxicity existed, especially
      in individuals treated with gemcitabine (P = 0.006) or cisplatin (P = 0.008), and
      in male patients (P = 0.02) or younger patients (P = 0.01). CONCLUSION: Our study
      confirmed that rs11614913 in hsa-miR-196a2 was associated with severe toxicity in
      lung cancer patients, and might help to improve individualized therapy in the
      future.

PMID- 23143627
TI  - Is identification of anti-SSA and/or -SSB antibodies necessary in serum samples
      referred for antinuclear antibodies testing?
AB  - BACKGROUND: Anti-SSA and -SSB antibodies are clinically important antinuclear
      antibodies in patients with systemic rheumatic diseases. METHODS: We evaluated
      fluorescence characteristics and clinical significance of anti-SSA and -SSB and
      explored whether identification of these antibodies was necessary in clinical
      application. RESULTS: Of 4,978 consecutive samples, 259 showed anti-SSA or -SSB
      reactivity, clinical information of which were analyzed. Compared with SSA+SSB-
      and SSA-SSB+ group, SSA+SSB+ group showed a lower proportion (0.5%) of negative
      specimens detected with antinuclear antibody assay and a higher proportion
      (53.5%) of specimens with high titer. Anti-SSA- and/or -SSB-positive samples
      presented various patterns. However, 64.6% of SSA+SSB+ samples presented speckled
      pattern, significantly higher than SSA+SSB- and SSA-SSB+ samples. A total of 475
      specimens containing anti-SSA or -SSB were obtained from 302 individuals.
      Clinical information was obtained for 259 of them, which were further analyzed.
      The prevalence of Sjogren syndrome (SS) was significantly higher, and that of
      other diseases was lower in SSA+SSB+ than in SSA+SSB- group. Of the 259
      individuals, 71 anti-SSA- and/or -SSB-positive patients had blood drawn on 2 or
      more occasions over the 2-year study period. The number of tests per patient was
      2.7 +/- 1.1. In 7 of the 71 patients, anti-SSA was observed in some but not all
      samples, so was anti-SSB in 6. CONCLUSION: In conclusion, the identification of
      anti-SSA and -SSB antibodies is necessary, when corresponding diseases are
      suspected. The specificity of anti-SSA for the diagnosis of SS could be improved,
      when combined with anti-SSB. SS patients need not be identified frequently for
      anti-SSA and -SSB because of their stability.

PMID- 23143629
TI  - A comparative study of apoptosis in placentas of normal and preeclamptic Indian
      pregnant women by TUNEL assay and M30 immunostaining.
AB  - BACKGROUND: Preeclampsia is a unique life-threatening disorder of human pregnancy
      associated with the abnormal placentation caused by the inadequate trophoblastic
      invasion due to altered apoptosis of these cells. The aim of the present study
      was to assess and compare the apoptosis in trophoblastic cells in various zones
      (villous and extravillous) of placentas of preeclamptic and normotensive
      nonproteinuric pregnant women. METHODS: Hematoxylin eosin staining, TUNEL assay
      and M30 immunostaining techniques were used for studying apoptosis in
      trophoblastic cells of placentas of two groups. The results of apoptotic indices
      by these techniques were compared in preeclamptic group. RESULTS: The TUNEL
      apoptotic indices were higher in all the zones of placentas of preeclamptic group
      as compared to control group though the results were not statistically
      significant. M30 immunostaining also gave higher apoptotic indices in all the
      zones of preeclamptic placentas as compared to the normal group but the result of
      apoptotic index of basal plate was not statistically significant. M30
      immunostaining was absent in stromal cells. CONCLUSION: In our study, the
      trophoblastic apoptotic rates were more in villous as well as extravillous zones
      of preeclamptic placentas as compared to normal placentas and M30 immunostaining
      was found to be more sensitive and specific for the apoptotic trophoblastic cells
      as compared to TUNEL assay.

PMID- 23143628
TI  - Etiology and survival of aplastic anemia: a study based on clinical
      investigation.
AB  - BACKGROUND: Management of aplastic anemia is etiology driven, whether
      constitutional or acquired. Age, gender, and severity of disease also play
      crucial role in the survival of aplastic anemia. Since, inadequate data are
      available from India, the present study was conducted with the aim to evaluate
      the etiology and survival of aplastic anemia. METHODS: Three hundred patients
      were enrolled between May 2007 and April 2010. Severity analysis and chromosomal
      breakage study was performed and patients were followed up to calculate the
      survival rate. RESULTS: Only 9.4% of the cases demonstrated the evidence of
      constitutional disease. Patients with acquired disease showed a significantly
      higher odd ratio for hepatitis. Overall survival was found to be independent of
      the gender and inherited etiology. Phenotype resembling to constitutional disease
      was present in only 22.22% (6/27) of patients. Similar ratio of the
      constitutional and acquired disease in both the age groups was observed.
      CONCLUSION: Irrespective of the age and phenotype, chromosomal breakage study
      should be mandatory for all patients with aplastic anemia. Hepatitis as a
      preceding event may be associated with the cause of aplastic anemia. Young age
      and less severe disease were strongly associated with better survival. Lack of
      tertiary care facility in the country, time lag between diagnosis and treatment,
      and unaffordability to abide the treatment cost could be the major contributory
      factors for poorer survival.

PMID- 23143630
TI  - Free circulating tumor DNA as a diagnostic marker for breast cancer.
AB  - BACKGROUND: Cell-free DNA (cfDNA) in the plasma of patients with both malignant
      and benign breast lesions was analyzed to determine whether the findings may have
      diagnostic and prognostic implications and to analyze the association between the
      levels of cfDNA and prognostic parameters. METHODS: Plasma samples were obtained
      from 99 subjects; 42 with breast cancer (BC), 30 with benign breast lesions, and
      27 healthy women as normal controls. Circulatory cfDNA was extracted from the
      plasma samples and quantified using a real-time quantitative PCR method.
      Immunohistochemistry was done on formalin-fixed paraffin-embedded sections to
      evaluate the status of hormonal receptors (estrogen receptor [ER] and
      progesterone receptor [PR]), and the protein expression of both Her2/neu and
      Topoisomerase IIalpha. RESULTS: The level of cfDNA in the BC group was
      significantly higher than in the benign lesions and control groups. cfDNA level
      was associated with malignant tumor size, lymph node involvement, stage, and
      grade as well as Her2/neu and Topoisomerase IIalpha expression, while it was not
      associated with ER or PR status. CONCLUSIONS: The present study suggests that the
      level of cfDNA can be easily quantified using plasma samples. Thus, level of
      plasma cfDNA might constitute an important noninvasive diagnostic and prognostic
      valuable tool in cancer breast patients' management.

PMID- 23143631
TI  - Urinary N-acetyl-beta-D-glucosaminidase levels are positively correlated with 2
      hr plasma glucose levels during oral glucose tolerance testing in prediabetes.
AB  - BACKGROUND: Urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion is increased
      in patients with impaired glucose tolerance (IGT). This study investigated when
      during the oral glucose tolerance test (OGTT) the plasma glucose, urine glucose,
      and insulin levels correlate most strongly with urinary N-acetyl-beta-d
      glucosaminidase (NAG) levels in prediabetic subjects. METHODS: The OGTT was
      administered to 80 subjects who had not yet received a diagnosis of diabetes
      mellitus (DM) and in whom HbA1c levels were <=6.8% and fasting plasma glucose
      levels were <7.0 mmol/l. Forty-two subjects had normal glucose tolerance (NGT),
      31 had impaired glucose tolerance (IGT), and 7 had DM according to World Health
      Organization criteria. Serum levels of cystatin C, the estimated glomerular
      filtration rate, the urinary albumin-to-creatinine (Cr) ratio, urinary and serum
      beta2-microglobulin, and urinary NAG were measured as markers of renal function.
      RESULTS: NAG levels were significantly higher in subjects with DM and in subjects
      with IGT than in subjects with NGT. No significant associations were observed
      between glycemic status and other markers of renal function. Multiple linear
      regression analysis showed that the NAG level was positively correlated with
      plasma glucose levels at 120 min of the OGTT and was associated with the glycemic
      status of prediabetic patients. CONCLUSION: These results suggest that
      postprandial hyperglycemia is an independent factor that causes renal tubular
      damage in prediabetes patients.

PMID- 23143632
TI  - Evaluation of turbidimetric inhibition immunoassay (TINIA) and HPLC methods for
      glycated haemoglobin determination.
AB  - BACKGROUND: Various factors may affect the accuracy of hemoglobin (Hb) A1c
      measurements that are widely used to monitor glycemic control in diabetic
      patients. This study was aimed to compare the values of HbA1c obtained by two
      different methods, Roche Tina-quant second and thirdgeneration HbA1c assays based
      on the turbidimetric inhibition immunoassay (TINIA), and high-performance liquid
      chromatography (HPLC) cation-exchange method used by Arkray Adams HA-8160
      analyzer. METHODS: Measurements of HbA1c were carried out in blood samples from
      2,917 patients using above-mentioned methods. Linear regression was used for the
      correlation analysis and linear equations. Bland-Altman plots were performed from
      method comparison data using MedCalc statistical software. RESULTS: For the low
      control, the second generation Tina-quant assay had within-run and between-run
      CVs 0.8% and 0.9%; for the high control within-run and between-run CVs were 1%
      and 0.96%, respectively. HPLC method for the low control had within-run CV 1% and
      between-run CV 1.3%; for the high control within-run CV was 0.6% and between-run
      CV was 0.9%. CONCLUSION: There was a good concordance between the results of
      TINIA and HPLC methods (y = 1.091x - 0.363; r(2)  = 0.96).

PMID- 23143633
TI  - Simultaneous determination of the combined drugs of ceftriaxone sodium,
      metronidazole, and levofloxacin in human urine by high-performance liquid
      chromatography.
AB  - AIM: To develop a new high-performance liquid chromatography (HPLC) method for
      simultaneous determination of the combined drugs (ceftriaxone sodium,
      metronidazole, and levofloxacin) in human urine. METHODS: Ceftriaxone sodium,
      metronidazole, and levofloxacin were separated on a Kromasil 100-5 C18 (250 mm *
      4.6 mm, 5 MUm, AKZO NOBEL, Bohus, Sweden) analytical column, using the mobile
      phase consisted of 1.5 mM KH(2) PO(4)  (pH 4.5) with 0.0125% triethylamine
      methnol (70:30, v/v). Ceftriaxone sodium, metronidazole, and levofloxacin were
      detected by a photodiode-array detector at 247, 320, 292 nm, respectively.
      RESULTS: Under optimal conditions, the effective separation of ceftriaxone
      sodium, metronidazole, and levofloxacin was achieved. A good linearity with the
      correlation coefficients more than 0.999 was demonstrated. The detection limits
      of ceftriaxone sodium, metronidazole, and levofloxacin were 0.05, 0.01, and 0.25
      MUg/ml, respectively, and the average recoveries in human urine were in the range
      from 97.73 to 100.7% with the average relative standard deviation (RSD) in the
      range of 2.5% and 3.0%. CONCLUSION: The proposed method was sensitive, accurate,
      and rapid. This work may provide a reference for clinical rational drug use and
      methodology for the pharmacokinetics study of the combined drugs.

PMID- 23143634
TI  - Mean platelet volume in neonatal sepsis.
AB  - BACKGROUND: The aim of this study was to investigate any changes in mean platelet
      volume (MPV) in patients with neonatal sepsis (NS). METHODS: Subjects were
      stratified into two groups: proven sepsis (Group 1a) and clinical sepsis (Group
      1b). The control group (Group 2) consisted of healthy newborns matched for
      gestational age and birth weight. RESULTS: A total of 100 patients with NS (35
      with proven sepsis and 65 with clinical sepsis) and 50 healthy controls were
      enrolled. A comparison of markers of sepsis obtained at baseline revealed white
      blood cell count (WBC), C-reactive protein (CRP), interleukin-6 (IL-6), and MPV
      levels to be significantly higher in newborns with sepsis compared to healthy
      controls (P = 0.01, <0.001, <0.001, and 0.001, respectively). Mean baseline serum
      levels of CRP and MPV were significantly higher in Group 1a compared to Group 1b
      (P = 0.003, P = 0.007, respectively), whereas the difference between group with
      regards to baseline serum levels of IL-6 and platelet count was statistically
      insignificant (P = 0.14, P = 0.28, respectively). CONCLUSION: This is the first
      study to demonstrate a statistically significant difference with regard to
      baseline MPV values between patients with sepsis (proven or clinical) and healthy
      controls.

PMID- 23143635
TI  - Red cell distribution width can predict intestinal atrophy in selected patients
      with celiac disease.
AB  - BACKGROUND: Red cell distribution width (RDW) has been shown as a distinctive
      marker of mortality and morbidity in a wide spectrum of conditions related to
      systemic inflammation or deficiency of antioxidant nutrients. OBJECTIVE: We aimed
      to investigate the predictive value of RDW in detection of intestinal atrophy in
      celiac disease (CD). METHODS: Iron indices and RDW were studied in 49 patients
      with CD to evaluate the utilization of RDW as a predictive marker for presence of
      intestinal atrophy. RESULTS: Sixty-nine percent of patients had iron deficiency
      at initial presentation and 89% had abnormal RDW defined as >14. Receiver
      operating characteristics curves of RDW has been found to be a predictive of
      intestinal atrophy at levels higher than 17.25 (68% sensitivity and 85%
      specificity). In patients with transglutaminase antibody IgA titers >200 U/l, RDW
      level >17.75 showed 76% sensitivity and 100% specificity for intestinal atrophy.
      CONCLUSIONS: We suggest that RDW can be used as a surrogate marker of atrophy in
      patients with iron deficiency and suspected CD. In addition, the sensitivity,
      specificity, negative and positive predictive values of RDW increases when used
      in combination with high levels of transglutaminase IgA antibody.

PMID- 23143636
TI  - Simulated moose (Alces alces L.) browsing increases accumulation of secondary
      metabolites in bilberry (Vaccinium myrtillus L.) along gradients of habitat
      productivity and solar radiation.
AB  - We have addressed the impact of moose (Alces alces L.) on accumulation of
      secondary metabolites, lignin, and nitrogen in bilberry (Vaccinium myrtillus L.)
      along gradients of habitat productivity and solar radiation. The study was
      conducted within a long-term research project on direct and indirect impacts of
      moose on the ecosystem. In the experiment, browsing, defecation, and urination
      corresponding to four different moose densities were simulated for eight years
      before bilberry tissue was collected and analyzed. Some quantitatively dominant
      flavonoids were affected by the simulated moose browsing and by habitat
      productivity and light. The content of flavonoids increased with increasing moose
      density and light, and decreased with increasing habitat productivity. The higher
      concentration of secondary metabolites in bilberry from nutrient-poor sites may
      have resulted from the increased photosynthesis relative to growth, which
      facilitated secondary metabolism. The higher concentration of secondary
      metabolites in plants subjected to simulated moose- herbivory might have been
      caused in part by loss of biomass. In addition, in areas with high biomass loss,
      i.e., high moose density, a more open canopy was created and more solar radiation
      could have induced secondary metabolism.

PMID- 23143637
TI  - Platelet rich fibrin: a new paradigm in periodontal regeneration.
AB  - Among the great challenges facing clinical research is the development of
      bioactive surgical additives regulating inflammation and increasing healing.
      Although the use of fibrin adhesives and platelet-rich plasma (PRP) is well
      documented, they have their own limitations. Hence, reconstructive dental
      surgeons are looking for an "edge" that jump starts the healing process to
      maximize predictability as well as the volume of regenerated bone. Overcoming the
      restrictions related to the reimplantation of blood-derived products, a new
      family of platelet concentrate, which is neither a fibrin glue nor a classical
      platelet concentrate, was developed in France. This second generation platelet
      concentrate called platelet-rich fibrin (PRF), has been widely used to accelerate
      soft and hard tissue healing. Its advantages over the better known PRP include
      ease of preparation/application, minimal expense, and lack of biochemical
      modification (no bovine thrombin or anticoagulant is required). This article
      serves as an introduction to the PRF "concept" and its potential clinical
      applications with emphasis on periodontal regeneration. 

PMID- 23143638
TI  - [Treatment of MRSA infections].

PMID- 23143639
TI  - KR-31543 reduces the production of proinflammatory molecules in human endothelial
      cells and monocytes and attenuates atherosclerosis in mouse model.
AB  - KR-31543, (2S, 3R, 4S)-6-amino-4-[N-(4-chlorophenyl)- N-(2-methyl-2H-tetrazol-5
      ylmethyl) amino]-3,4-dihydro- 2-dimethyoxymethyl-3-hydroxy-2-methyl-2H-1-benz
      opyran is a new neuroprotective agent for ischemiareperfusion damage. It has also
      been reported that KR-31543 has protective effects on lipid peroxidation and H2O2
      induced reactive oxygen species production. In this study, we investigated the
      anti-inflammatory and anti-atherogenic properties of KR-31543. We observed that
      KR-31543 treatment reduced the production of MCP-1, IL-8, and VCAM-1 in HUVECs,
      and of MCP-1 and IL-6 in THP-1 human monocytes. We also examined the effect of KR
      31543 on monocytes migration in vitro. KR-31543 treatment effectively reduced the
      migration of THP-1 human monocytes to the HUVEC monolayer in a dose-dependent
      manner. We next examined the effects of this compound on atherogenesis in LDL
      receptor deficient (Ldlr -/-) mice. After 10 weeks of western diet, the formation
      of atherosclerotic lesion in aorta was reduced in the KR-31543-treated group
      compared to the control group. The accumulation of macrophages in lesion was also
      reduced in KR-31543 treated group. However, the plasma levels of total
      cholesterol, HDL, LDL, and triglyceride were not affected by KR-31543 treatment.
      Taken together, these results show that KR-31543 has anti-inflammatory properties
      on human monocytes and endothelial cells, and inhibits fatty streak lesion
      formation in mouse model of atherosclerosis, suggesting the potential of KR-31543
      for the treatment for atherosclerosis.

PMID- 23143640
TI  - Reflux-associated oxygen desaturations: usefulness in diagnosing reflux-related
      respiratory symptoms.
AB  - BACKGROUND: Current diagnostic techniques establishing gastroesophageal reflux
      disease as the underlying cause in patients with respiratory symptoms are poor.
      Our aim was to provide additional support to our prior studies suggesting that
      the association between reflux events and oxygen desaturations may be a useful
      discriminatory test in patients presenting with primary respiratory symptoms
      suspected of having gastroesophageal reflux as the etiology. METHODS: Thirty
      seven patients with respiratory symptoms, 26 with typical symptoms, and 40
      control subjects underwent simultaneous 24-h impedance-pH and pulse oximetry
      monitoring. Eight patients returned for post-fundoplication studies. RESULTS: The
      median number (interquartile range) of distal reflux events associated with
      oxygen desaturation was greater in patients with respiratory symptoms (17 (9-23))
      than those with typical symptoms (7 (4-11, p < 0.001)) or control subjects (3 (2
      6, p < 0.001)). A similar relationship was found for the number of proximal
      reflux-associated desaturations. Repeat study in seven post-fundoplication
      patients showed marked improvement, with reflux-associated desaturations
      approaching those of control subjects in five patients; 20 (9-20) distal
      preoperative versus 3 (0-5, p = 0.06) postoperative; similar results were
      identified proximally. CONCLUSIONS: These data provide further proof that reflux
      associated oxygen desaturations may discriminate patients presenting with primary
      respiratory symptoms as being due to reflux and may respond to antireflux
      surgery.

PMID- 23143641
TI  - Over-diagnosis of laryngopharyngeal reflux as the cause of hoarseness.
AB  - The objectives of this study were: (1) to determine the percentage of patients
      seen in a private laryngology clinic with voice-related disorders previously
      diagnosed with and treated for laryngopharyngeal reflux (LPR); (2) to determine
      how many of those patients are found to have disorders other than LPR as a cause
      for their voice disorder. A retrospective, chart-review analysis of new patients
      was conducted from January 2005 through December 2007 in a private laryngology
      clinic setting. Patients with a previous diagnosis of LPR as the cause of
      hoarseness, with or without anti-reflux treatment were included. Incomplete
      charts and patients with additional diagnoses besides LPR where excluded. Patient
      charts were analyzed in search of different variables including chief complaint,
      previous medications and final diagnosis among others. 784 consecutive charts
      were reviewed. Inclusion criteria were met in 105 charts. 82 % had no improvement
      or felt worse after previous anti-reflux treatment while 18 % had significant or
      mild improvement. However, all patients remained with some degree of hoarseness.
      Final diagnosis by the author was diverse though none of the patients had
      laryngopharyngeal reflux as a final diagnosis and none of them noted worsening of
      their voice after respective treatment. Only 6 % felt the same after treatment
      and 9 % could not be found for follow-up. LPR has become an over-diagnosed
      entity. With a thorough history, vocal capability testing and physical exam, an
      accurate diagnosis for hoarseness can be made in the vast majority of cases. LPR
      may not be the cause of voice disorders and should not be assigned as a de facto
      diagnosis just because the cause of hoarseness is not readily identifiable.

PMID- 23143642
TI  - Technical and functional hearing results after unilateral stapes surgery for
      otosclerosis at Cluj-Napoca University Hospital.
AB  - The aim of this study was to assess the hearing results after unilateral stapes
      surgery for otosclerosis at Cluj-Napoca University Hospital, and to evaluate
      surgical trauma to the inner ear in these patients. The medical records of 387
      consecutive patients who underwent unilateral stapes surgery were reviewed.
      Hearing results were evaluated according to the 1995 American Academy of
      Otolaryngology-Head and Neck Surgery Committee on Hearing and Equilibrium
      guidelines and the Glasgow benefit plot. In addition we used Amsterdam plot to
      give an overview on air conduction gain and bone-conduction differences on an
      individual level. Results were analyzed separately for patients with preoperative
      unilateral, bilateral asymmetrical, and bilateral symmetrical hearing loss.
      Despite good technical hearing results after surgery (closure of the air-bone gap
      to <=20 dB in 92% of patients, air conduction gain of 24 +/- 10.00 dB), only 37%
      of patients achieved functionally normal, symmetrical hearing. Our results
      indicated that the pattern of preoperative hearing impairment in patients with
      otosclerosis can predict postoperative functional hearing results. The type of
      preoperative hearing impairment had.

PMID- 23143643
TI  - Involvement of peripheral vestibular nerve in individuals with auditory
      neuropathy.
AB  - The vestibulocochlear nerve is a sensory nerve that serves the organs of hearing
      and equilibrium. Neuropathies of the nerve, particularly auditory neuropathy may
      be caused by primary demyelination or by axonal diseases. In disorders affecting
      the cochlear nerve, it is probable that the vestibular nerve is involved as well.
      There are isolated reports of the involvement of the inferior vestibular nerve
      (using vestibular-evoked myogenic potentials) in individuals with AN. However,
      there is a dearth of information on the involvement of the superior vestibular
      nerve and other functions such as optokinetic, saccade and vestibulo-occular
      reflex. A total of three subjects diagnosed as having auditory neuropathy,
      underwent an extensive vestibular assessment consisting of clinical tests of
      stability (Romberg, Fukuda stepping test), administration of dizziness
      questionnaire developed by Maryland hearing and balance centre, cervical
      vestibular-evoked myogenic potentials and a standard electronystagmography test
      battery. In the present study, the entire subject population assessed showed
      hypofunctional caloric responses and absent VEMPs. Two out of the three subjects
      were asymptomatic of vestibular dysfunction. On the clinical tests of stability,
      two subjects showed deviations to the right, while one subject performed
      normally. Thus, the present study indicates a possible involvement of peripheral
      vestibular nerve involvement in individuals with auditory neuropathy. 

PMID- 23143644
TI  - Stereocontrolled total synthesis of (+)-UCS1025A.

PMID- 23143645
TI  - Long noncoding RNA CCAT1, which could be activated by c-Myc, promotes the
      progression of gastric carcinoma.
AB  - PURPOSE: Long noncoding RNAs (lncRNAs) have been shown to have functional roles
      in cancer biology and are deregulated in many tumors. The specific aim of this
      study was to determine the role of a long noncoding RNA CCAT1 in the progression
      of gastric carcinoma and discover which factors contribute to the deregulation of
      CCAT1. METHODS: A computational screen of CCAT1 promoter was conducted to search
      for transcription-factor-binding sites. The association of c-Myc with the CCAT1
      promoter in vivo was tested by chromatin immunoprecipitation assay. CCAT1
      promoter activities were examined by luciferase reporter assay. The function of
      the c-Myc binding site in the CCAT1 promoter region was tested by a promoter
      assay with nucleotide substitutions in the putative E-box. The effect of CCAT1 on
      gastric carcinoma cell proliferation and migration was tested using in vitro cell
      proliferation and migration assays. RESULTS: CCAT1 levels were markedly increased
      in gastric carcinoma tissues compared with normal tissues. c-Myc directly binds
      to the E-box element in the promoter region of CCAT1, and when ectopically
      expressed increased promoter activity and expression of CCAT1. Nucleotide
      substitutions in the E-box element in the promoter region abrogated c-Myc
      dependent promoter activation. The expression of CCAT1 and c-Myc shows strong
      association in gastric carcinomas. Moreover, abnormally expressed CCAT1 promotes
      cell proliferation and migration. CONCLUSIONS: These data suggest that c-Myc
      induction of CCAT1 holds an important role in gastric carcinoma and implicate the
      potential application of CCAT1 in the treatment of gastric carcinoma.

PMID- 23143646
TI  - Overexpression of focal adhesion kinase correlates with increased lymph node
      metastasis and poor prognosis in non-small-cell lung cancer.
AB  - BACKGROUND: The aim of this study was to investigate whether focal adhesion
      kinase (FAK) overexpression correlates with lymph node metastases and prognosis.
      METHODS: The protein expression of FAK was investigated in 153 paraffin-embedded
      tissues by immunohistochemical analysis and then correlated with various
      clinicopathologic parameters. FAK mRNA level was detected with quantitative RT
      PCR in 57 NSCLC frozen tissues and 20 normal matched tissues. RESULTS:
      Immunohistochemistry showed FAK overexpression was significantly associated with
      positive lymph node metastasis and more advanced disease stage of NSCLCs and
      adenocarcinoma subtype; real-time PCR also indicated a statistically significant
      correlation between increased FAK mRNA level and the presence of nodal
      metastases. Moreover, in survival analysis, FAK overexpression was significantly
      associated with worse overall survival. CONCLUSIONS: FAK overexpression is a
      promising pathological factor to predict aggressive behavior and prognosis in
      patients with NSCLC, particularly in the adenocarcinoma subtype.

PMID- 23143647
TI  - Centromere positions in chicken and Japanese quail chromosomes: de novo
      centromere formation versus pericentric inversions.
AB  - Chicken (Gallus gallus domesticus, GGA) and Japanese quail (Coturnix coturnix
      japonica, CCO) karyotypes are very similar. They have identical chromosome number
      (2n = 78) and show a high degree of synteny. Centromere positions on the majority
      of orthologous chromosomes are different in these two species. To explore the
      nature of this divergence, we used high-resolution comparative fluorescent in
      situ hybridization mapping on giant lampbrush chromosomes (LBCs) from growing
      oocytes. We applied 41 BAC clones specific for GGA1, 2, 3, 11, 12, 13, 14, and 15
      to chicken and quail LBCs. This approach allowed us to rule out a pericentric
      inversion earlier proposed to explain the difference between GGA1 and CCO1. In
      addition to a well-established large-scale pericentric inversion that
      discriminates GGA2 and CCO2, we identified another, smaller one in the large
      inverted region. For the first time, we described in detail inversions that
      distinguish GGA3 from CCO3 and GGA11 from CCO11. Despite the newly identified and
      confirmed inversions, our data suggest that, in chicken and Japanese quail, the
      difference in centromere positions is not mainly caused by pericentric inversions
      but is instead due to centromere repositioning events and the formation of new
      centromeres. We also consider the formation of short arms of quail
      microchromosomes by heterochromatin accumulation as a third scenario that could
      explain the discrepancy in centromeric indexes.

PMID- 23143648
TI  - High-resolution mapping and transcriptional activity analysis of chicken
      centromere sequences on giant lampbrush chromosomes.
AB  - Exploration into morphofunctional organisation of centromere DNA sequences is
      important for understanding the mechanisms of kinetochore specification and
      assembly. In-depth epigenetic analysis of DNA fragments associated with
      centromeric nucleosome proteins has demonstrated unique features of centromere
      organisation in chicken karyotype: there are both mature centromeres, which
      comprise chromosome-specific homogeneous arrays of tandem repeats, and recently
      evolved primitive centromeres, which consist of non-tandemly organised DNA
      sequences. In this work, we describe the arrangement and transcriptional activity
      of chicken centromere repeats for Cen1, Cen2, Cen3, Cen4, Cen7, Cen8, and Cen11
      and non-repetitive centromere sequences of chromosomes 5, 27, and Z using highly
      elongated lampbrush chromosomes, which are characteristic of the diplotene stage
      of oogenesis. The degree of chromatin packaging and fine spatial organisations of
      tandemly repetitive and non-tandemly repetitive centromeric sequences
      significantly differ at the lampbrush stage. Using DNA/RNA FISH, we have
      demonstrated that during the lampbrush stage, DNA sequences are transcribed
      within the centromere regions of chromosomes that lack centromere-specific tandem
      repeats. In contrast, chromosome-specific centromeric repeats Cen1, Cen2, Cen3,
      Cen4, Cen7, Cen8, and Cen11 do not demonstrate any transcriptional activity
      during the lampbrush stage. In addition, we found that CNM repeat cluster
      localises adjacent to non-repetitive centromeric sequences in chicken
      microchromosome 27 indicating that centromere region in this chromosome is repeat
      rich. Cross-species FISH allowed localisation of the sequences homologous to
      centromeric DNA of chicken chromosomes 5 and 27 in centromere regions of quail
      orthologous chromosomes.

PMID- 23143649
TI  - Hierarchical radial and polar organisation of chromosomes in human sperm.
AB  - It is well established that chromosomes occupy distinct positions within the
      interphase nuclei, conferring a potential functional implication to the genome.
      In addition, alterations in the nuclear organisation patterns have been
      associated with disease phenotypes (e.g. cancer or laminopathies). The human
      sperm is the smallest cell in the body with specific DNA packaging and the
      mission of delivering the paternal genome to the oocyte during fertilisation.
      Studies of nuclear organisation in the sperm have postulated nonrandom chromosome
      position and have proposed a chromocentre model with the centromeres facing
      toward the interior and the telomeres toward the periphery of the nucleus. Most
      studies have assessed the nuclear address in the sperm longitudinally
      predominantly using centromeric or telomeric probes and to a lesser extent with
      whole chromosome paints. To date, studies investigating the radial organisation
      of human sperm have been limited. The purpose of this study was to utilise whole
      chromosome paints for six clinically important chromosomes (18, 19, 21, 22, X,
      and Y) to investigate nuclear address by assessing their radial and longitudinal
      nuclear organisation. A total of 10,800 sperm were analysed in nine
      normozoospermic individuals. The results have shown nonrandom chromosome position
      for all chromosomes using both methods of analysis. We present novel radial and
      polar analysis of chromosome territory localization within the human sperm
      nucleus. Specifically, a hierarchical organisation was observed radially with
      chromosomes organised from the interior to the periphery (chromosomes 22, 21, Y,
      X, 19, and 18 respectively) and polar organisation from the sperm head to tail
      (chromosomes X, 19, Y, 22, 21, and 18, respectively). We provide evidence of
      defined nuclear organisation in the human sperm and discuss the function of
      organisation and potential possible clinical ramifications of these results in
      regards to male infertility and early human development.

PMID- 23143650
TI  - Four 3D "brick-wall"-like metal-organic frameworks with a flexible ligand of
      (S,S,R,R)-1,2,3,4-cyclopentanetetracarboxylic acid: crystal structures,
      luminescent and magnetic properties.
AB  - To investigate the conformation of cyclopentanetetracarboxylic acid, four new
      "brick-wall"-like metal-organic frameworks have been synthesized from
      hydrothermal reactions with different metal salts, (S,S,R,R)-1,2,3,4
      cyclopentanetetracarboxylic acid (H(4)cptc) and auxiliary N-donor ligands,
      namely, Cu(2)(S,S,R,R-cptc)(bpe)(H(2)O)(2).2H(2)O (1), Co(2)(S,S,R,R
      cptc)(bpe)(0.5)(H(2)O)(2).2H(2)O (2), Cd(4)(S,S,R,R
      cptc)(2)(bpa)(2)(H(2)O)(5).2H(2)O (3) and Co(2)(S,S,R,R
      cptc)(bpy)(0.5)(H(2)O)(2).2(H(2)O) (4) (bpe = 4-(2-(pyridine-4-yl)vinyl)pyridine,
      bpa = 4-(2-(pyridine-4-yl)ethyl)pyridine, bpy = 4-(pyridine-4-yl)pyridine). The
      complexes were further characterized by single-crystal X-ray diffraction, power X
      ray diffraction, FT-IR spectra, fluorescent measurements and variable-temperature
      magnetic susceptibility measurements. The results of the structural
      investigations show that 1 is a charming (3,3,4)-trinodal architecture, 3 is an
      interesting trinodal (3,4,5)-connected architecture, and 2 and 4 are
      isostructural, which are both (4,5)-connected networks. In addition, the magnetic
      measurements indicate that 2 and 4 show weak antiferromagnetic interactions, and
      the fluorescent measurement shows the strong solid-state fluorescent emission at
      room temperature for 3.

PMID- 23143651
TI  - Successful pregnancy and delivery on prasugrel treatment: considerations for the
      use of dual antiplatelet therapy during pregnancy in clinical practice.
AB  - Ischemic heart disease is uncommon during pregnancy, occurring in approximately
      1/10,000 pregnancies resulting in live births. However, the increased age and
      fertility of mothers has suggested that the coexistence of pregnancy and coronary
      artery disease is likely to increase. A subject of debate is the management of
      dual antiplatelet therapy among pregnant women. The potential teratogeneous
      effects, particularly with regards to thienopyridines, on the fetus are not fully
      established. In addition, the use of dual antiplatelet therapy is associated with
      an increased risk for bleeding events, raising concerns in the peripartum period
      with regards to the route of delivery and choice of anesthestic techniques.
      Limited data and experience is available with clopidogrel, the most commonly used
      thienopyridine. Prasugrel is third generation thienopyridine recently introduced
      into clinical practice with ever growing use in the setting of acute coronary
      syndrome patients undergoing percutaneous coronary interventions. The present
      manuscript describes the first case report of a pregnancy while on prasugrel
      therapy. 

PMID- 23143652
TI  - Transcatheter aortic valve implantation and bleeding: incidence, predictors and
      prognosis.
AB  - Peri-procedural bleeding complications are feared adverse events in patients
      undergoing transcatheter aortic valve implantation (TAVI). Little is known about
      the implications of peri-procedural bleeding on clinical outcome. In a
      prospective single-center registry of consecutive patients undergoing TAVI, we
      investigated incidence, predictors and clinical consequences of life-threatening
      and major bleeding as defined by the Valve Academic Research Consortium. Among
      389 consecutive patients undergoing TAVI by a transfemoral (79.2%), transapical
      (19.6%) or trans-subclavian (1.3%) approach between July 2007 and October 2011,
      life-threatening or major peri-procedural bleeding events occurred in 64 (16.4%)
      and 125 patients (32.1%), respectively. Patients with peri-procedural bleeding
      events had a higher logistic EuroSCORE, more advanced renal disease, and were
      more symptomatic as assessed by New York Heart Association functional class at
      baseline as compared to patients with no bleeding. Life-threatening bleeding was
      associated with a higher all-cause (17.2 vs. 5.6 vs. 3.0%, p < 0.001) and
      cardiovascular mortality (10.9 vs. 5.6 vs. 2.5%, p = 0.02) at 30 days compared to
      patients with major bleeding or no bleeding. Multivariate analysis identified
      transapical access (OR 2.6, 95% CI 1.4-4.8; p = 0.002), glomerular filtration
      rate <30 ml/min (OR 2.3, 95% CI 1.1-4.7, p = 0.031), and diabetes (OR 1.8, 95% CI
      1.001-3.2, p = 0.049) as independent predictors of life-threatening, peri
      procedural bleeding. Life-threatening bleeding complications in patients
      undergoing TAVI are associated with increased mortality. Renal impairment,
      diabetes, and transapical approach were identified as independent risk factors
      for life-threatening bleeding events.

PMID- 23143653
TI  - Severe bone marrow failure associated with human parvovirus B19 infection in a
      case with no underlying disorder.

PMID- 23143654
TI  - An integrated physiology-based model for the interaction of RAA system biomarkers
      with drugs.
AB  - The renin angiotensin aldosterone system (RAAS) is a paramount target for the
      pharmacological treatment of cardiovascular diseases. As modeling and simulation
      techniques are becoming increasingly utilized in cardiovascular research, our aim
      was to develop a physiology-based model that describes the effect of different
      drugs at different doses on the RAAS and integrates physiology-based description
      drug pharmacokinetics (PK). First, a basic RAAS model was developed in which
      equations for drug effects were included and missing parameters estimated. Next,
      a physiology-based PK model for enalapril and enalaprilat was developed and
      coupled to the RAAS model. Simulation of the effects of angiotensin-converting
      enzyme inhibitors, angiotensin receptor blockers, and aliskiren administration on
      angiotensins I and II did not reveal significant overestimation or
      underestimation. For all drugs, the error numerics were acceptable. The model
      also encompassed the PK of intravenous and oral enalapril and its conversion to
      enalaprilat. In summary, we report a physiology-based model for the interaction
      of the RAAS biomarkers angiotensin I and II with enalapril, benazepril,
      aliskiren, and losartan that allows for an adequate description of the RAAS
      response after single administration of the drugs. Such a comprehensive
      description may lead to a better understanding of the effects of pharmacological
      interventions in the RAAS.

PMID- 23143655
TI  - L-arginine transport and nitric oxide synthesis in human endothelial progenitor
      cells.
AB  - Nitric oxide (NO) is an endogenous vasodilator molecule synthetized from L
      arginine by a family of nitric oxide synthases. In differentiated human
      endothelial cells, it is well known that L-arginine uptake via cationic amino
      acid transporters (y(+)/CAT) or system y(+)L is required for the NO synthesis via
      endothelial nitric oxide synthase, but there are no reports in human endothelial
      progenitor cell (hEPC). Therefore, we isolated hEPCs from peripheral blood of
      healthy donors and cultured them for either 3 (hEPC-3d) or 14 days (hEPC-14d) to
      characterize the L-arginine transport and NO synthesis in those cells. L-arginine
      transport and NO synthesis were analyzed in the presence or absence of N
      ethylmaleimide or L-nitroarginine methyl ester, as inhibitors of y(+)/CAT system
      and nitric oxide synthases, respectively. The results showed that L-arginine
      uptake is higher in hEPC-14d than in hEPC-3d. Kinetic parameters for L-arginine
      transport showed the existence of at least 2 transporter systems in hEPC: a high
      affinity transporter system (K(m)= 4.8 +/- 1.1 MUM for hEPC-3d and 6.1 +/- 2.4
      MUM for hEPC-14d) and a medium affinity transporter system (K(m) = 85.1 +/- 4.0
      MUM for hEPC-3d and 95.1 +/- 8 MUM for hEPC-14d). Accordingly, hEPC expressed
      mRNA and protein for CAT-1 (ie, system y(+)) and mRNA for 2 subunits of y(+)L
      system, yLAT1, and 4F2hc. Higher L-citruline production and NO bioavailability (4
      fold), and endothelial nitric oxide synthase expression (both mRNA and protein)
      were observed in hEPC-14d compared with hEPC-3d. Finally, the high L-citruline
      formation observed in hEPC-14d was blocked by N-ethylmaleimide. In conclusion,
      this study allowed to identity a functional L-arginine/NO pathway in two hEPC
      differentiation stages, which improves the understanding of the physiology of
      these precursor cells.

PMID- 23143656
TI  - Treatment efficacy of DNA lipid nanocapsules and DNA multimodular systems after
      systemic administration in a human glioma model.
AB  - BACKGROUND: We previously developed different types of DNA nanocarriers for
      systemic administration. Recently, the biodistribution profiles of these
      intravenously administered nanocarriers, DNA lipid nanocapsules (LNCs) and
      different multimodular systems (MMS), were analysed in healthy mice using in vivo
      biofluorescence imaging. METHODS: In the present study, the experiments were
      performed in an ectopic human U87MG glioma model in nude mice. First, the
      biodistribution profiles of intravenously administered multimodular systems
      delivering a plasmid DNA with a luciferase cassette were analysed using in vivo
      biofluorescence imaging. Afterwards, a systemic treatment with two long
      circulating DNA nanocarriers, poly(ethylene glycol) (PEG) DNA LNCs and galactose
      (GAL) DNA MMS dioleylamin-succinyl paromomycin (DOSP) was performed on this
      glioma model using a plasmid encoding the herpes simplex virus thymidine kinase
      (HSV-tk) and subsequent ganciclovir (GCV) treatment. RESULTS: The biodistribution
      profiles of the different DNA nanocarriers on this glioma model were similar to
      those observed on healthy animals and varied in function of their cationic lipid
      composition and their surface characteristics. Furthermore, PEG DNA LNCs and GAL
      DNA MMS DOSP showed a specific accumulation and some luciferase expression in the
      tumour tissue. The systemic treatment using the HSV-tk/GCV approach showed a
      tumour growth reduction compared to the nontreated mice cohort. CONCLUSIONS:
      These results are in good accordance with those obtained previously with PEG DNA
      LNCs in a human melanoma mouse model and highlight the potential use of GAL DNA
      MMS DOSP and PEG DNA LNCs as future therapeutics in glioma and other cancers.

PMID- 23143657
TI  - Cross-regulation between cardiac muscarinic acetylcholine receptors and beta
      adrenoceptors: lessons for use of knock-out mice.

PMID- 23143658
TI  - Extreme zinc tolerance in acidophilic microorganisms from the bacterial and
      archaeal domains.
AB  - Zinc can occur in extremely high concentrations in acidic, heavy metal polluted
      environments inhabited by acidophilic prokaryotes. Although these organisms are
      able to thrive in such severely contaminated ecosystems their resistance
      mechanisms have not been well studied. Bioinformatic analysis of a range of
      acidophilic bacterial and archaeal genomes identified homologues of several known
      zinc homeostasis systems. These included primary and secondary transporters, such
      as the primary heavy metal exporter ZntA and Nramp super-family secondary
      importer MntH. Three acidophilic model microorganisms, the archaeon 'Ferroplasma
      acidarmanus', the Gram negative bacterium Acidithiobacillus caldus, and the Gram
      positive bacterium Acidimicrobium ferrooxidans, were selected for detailed
      analyses. Zinc speciation modeling of the growth media demonstrated that a large
      fraction of the free metal ion is complexed, potentially affecting its toxicity.
      Indeed, many of the putative zinc homeostasis genes were constitutively expressed
      and with the exception of 'F. acidarmanus' ZntA, they were not up-regulated in
      the presence of excess zinc. Proteomic analysis revealed that zinc played a role
      in oxidative stress in At. caldus and Am. ferrooxidans. Furthermore, 'F.
      acidarmanus' kept a constant level of intracellular zinc over all conditions
      tested whereas the intracellular levels increased with increasing zinc exposure
      in the remaining organisms.

PMID- 23143659
TI  - Concentration- and schedule-dependent effects of chemotherapy on the angiogenic
      potential and drug sensitivity of vascular endothelial cells.
AB  - The anti-angiogenic activity of chemotherapy is both dose- and schedule
      dependent. While conventional maximum tolerated dose (MTD) chemotherapy exerts
      only mild and reversible anti-angiogenic effects, low-dose metronomic (LDM)
      chemotherapy was developed to specifically target tumour angiogenesis. However,
      the long-term effects of either MTD or LDM chemotherapy on vascular endothelial
      cells have never been investigated. Here, we demonstrated that repeated exposure
      to MTD and LDM chemotherapy differentially impact on the angiogenic potential and
      chemosensitivity of immortalized endothelial cells. Repeated MTD vinblastine
      treatment of vascular endothelial cells led to an increased proliferation rate
      and resistance to paclitaxel. In contrast, repeated LDM treatment with
      vinblastine or etoposide impaired the angiogenic potential of endothelial cells
      and increased their chemosensitivity. This effect was associated with a
      significant decrease in betaII- and betaIII-tubulin expression. Functional
      analysis using siRNA showed that silencing the expression of betaIII-tubulin in
      endothelial cells significantly decreased their capacity to form vascular
      structures and increased their sensitivity to the anti-angiogenic and vascular
      disrupting effects of chemotherapy, whereas silencing betaII-tubulin expression
      had no effect. Collectively our results show that LDM chemotherapy impairs the
      angiogenic potential of endothelial cells while increasing their chemosensitivity
      an effect at least in part mediated by the down-regulation of betaIII-tubulin
      expression. Furthermore, our study suggests that betaIII-tubulin represents an
      attractive therapeutic target to increase the anti-angiogenic effects of
      chemotherapy and overall anti-tumour efficacy.

PMID- 23143660
TI  - Ribonuclease 4 protects neuron degeneration by promoting angiogenesis,
      neurogenesis, and neuronal survival under stress.
AB  - Altered RNA processing is an underlying mechanism of amyotrophic lateral
      sclerosis (ALS). Missense mutations in a number of genes involved in RNA function
      and metabolisms are associated with ALS. Among these genes is angiogenin (ANG),
      the fifth member of the vertebrate-specific, secreted ribonuclease superfamily.
      ANG is an angiogenic ribonuclease, and both its angiogenic and ribonucleolytic
      activities are important for motor neuron health. Ribonuclease 4 (RNASE4), the
      fourth member of this superfamily, shares the same promoters with ANG and is co
      expressed with ANG. However, the biological role of RNASE4 is unknown. To
      determine whether RNASE4 is involved in ALS pathogenesis, we sequenced the coding
      region of RNASE4 in ALS and control subjects and characterized the angiogenic,
      neurogenic, and neuroprotective activities of RNASE4 protein. We identified an
      allelic association of SNP rs3748338 with ALS and demonstrated that RNASE4
      protein is able to induce angiogenesis in in vitro, ex vivo, and in vivo assays.
      RNASE4 also induces neural differentiation of P19 mouse embryonal carcinoma cells
      and mouse embryonic stem cells. Moreover, RNASE4 not only stimulates the
      formation of neurofilaments from mouse embryonic cortical neurons, but also
      protects hypothermia-induced degeneration. Importantly, systemic treatment with
      RNASE4 protein slowed weight loss and enhanced neuromuscular function of SOD1
      (G93A) mice.

PMID- 23143661
TI  - Feasibility of perfusion CT technique integrated into conventional 18FDG/PET-CT
      studies in lung cancer patients: clinical staging and functional information in a
      single study.
AB  - PURPOSE: To assess the additional functional vascular information and the
      relationship between perfusion measurements and glucose metabolism (SUVmax)
      obtained by including a perfusion CT study in a whole-body contrast-enhanced
      PET/CT protocol in primary lung cancer lesions. METHODS: Enrolled in this
      prospective study were 34 consecutive patients with a biopsy-proven diagnosis of
      lung cancer who were referred for contrast-enhanced PET/CT staging. This
      prospective study was approved by our institutional review board, and informed
      consent was obtained from all patients. Perfusion CT was performed with the
      following parameters: 80 kV, 200 mAs, 30 scans during intravenous injection of 50
      ml contrast agent, flow rate 5 ml/s. Another bolus of contrast medium (3.5 ml/s,
      80 ml, 60-s delay) was administered to ensure a full diagnostic contrast-enhanced
      CT scan for clinical staging. The perfusion CT data were used to calculate a
      range of tumour vascularity parameters (blood flow, blood volume and mean transit
      time), and tumour FDG uptake (SUVmax) was used as a metabolic indicator.
      Quantitative and functional parameters were compared and in relation to location,
      histology and tumour size. The nonparametric Kruskal-Wallis rank sum test was
      used for statistical analysis. RESULTS: A cut-off value of 3 cm was used
      according to the TNM classification to discriminate between T1 and T2 tumours
      (i.e. T1b vs. T2a). There were significant perfusion differences (lower blood
      volumes and higher mean transit time) between tumours with diameter >30 mm and
      tumours with diameter <30 mm (p < 0.05; blood volume 5.6 vs. 7.1 ml/100 g, mean
      transit time 8.6 vs. 3.9 s, respectively). Also there was a trend for blood flow
      to be lower in larger lesions (p < 0.053; blood flow 153.1 vs. 98.3 ml/100 g
      tissue/min). Significant inverse correlations (linear regression) were found
      between blood volume and SUVmax in tumours with diameter >30 mm in diameter.
      CONCLUSION: Perfusion CT combined with PET/CT is feasible technique that may
      provide additional functional information about vascularity and tumour
      aggressiveness as a result of lower perfusion and higher metabolism shown by
      larger lesions.

PMID- 23143662
TI  - Defining the role for dosimetry and radiobiology in combination therapies.

PMID- 23143663
TI  - Evidence for behavioral attractiveness of methoxylated aromatics in a dynastid
      scarab beetle-pollinated araceae.
AB  - Many plants attract their pollinators with floral scents, and these olfactory
      signals are especially important at night, when visual signals become
      inefficient. Dynastid scarab beetles are a speciose group of night-active
      pollinators, and several plants pollinated by these insects have methoxylated
      aromatic compounds in their scents. However, there is a large gap in our
      knowledge regarding the compounds responsible for beetle attraction. We used
      chemical analytical analyses to determine temporal patterns of scent emission and
      the composition of scent released from inflorescences of Philodendron selloum.
      The attractiveness of the main components in the scent to the dynastid scarab
      beetle Erioscelis emarginata, the exclusive pollinator of this plant, was
      assessed in field biotests. The amount of scent increased rapidly in the evening,
      and large amounts of scent were released during the activity time of the beetle
      pollinators. Inflorescences emitted a high number of compounds of different
      biosynthetic origin, among them both uncommon and also widespread flower scents.
      Methoxylated aromatic compounds dominated the scent, and 4-methoxystyrene, the
      most abundant compound, attracted E. emarginata beetles. Other compounds, such as
      (Z)-jasmone and possibly also the methoxylated aromatic compound 3,4
      dimethoxystyrene increased the attractiveness of 4-methoxystyrene. Methoxylated
      aromatics, which are known from other dynastid pollinated plants as well, are
      important signals in many scarab beetles in a different context (e.g.,
      pheromones), thus suggesting that these plants exploit pre-existing preferences
      of the beetles for attracting this group of insects as pollinators.

PMID- 23143664
TI  - Stylopsal: the first identified female-produced sex pheromone of strepsiptera.
AB  - A female-produced sex pheromone of Stylops muelleri was identified as an
      unusually branched saturated aldehyde (9R)-3,5-syn-3,5,9-trimethyldodecanal. We
      named it stylopsal. Its structure was established by using mass spectrometry,
      infrared spectroscopy, and organic synthesis of candidate compounds. The
      synthetic standard of (9R)-3,5-syn-3,5,9-trimethyldodecanal gave identical
      chromatographic and mass spectrometric data as the natural pheromone and also was
      active in electroantennographic and behavioral assays. The female fat body lipids
      contained the corresponding fatty acid, indicating a possible link between lipid
      metabolism and the pheromone biosynthesis.

PMID- 23143665
TI  - Monoclonal anti-TNF antibodies can elevate hemoglobin level in patients with
      ankylosing spondylitis.
AB  - Anemia is one of the extra-articular findings of ankylosing spondylitis (AS), and
      anti-TNF therapy has been shown benefit in patients with anemia associated AS. In
      this study, we aimed to evaluate and compare the effects of biological and non
      biological agents on hemoglobin levels in AS patients. One hundred consecutive
      patients who fulfilled ASAS criteria for AS were included in the study. Fifty
      four of the patients treated with anti-TNF agents (20 patients treated with
      infliximab, 20 patients with adalimumab, and 14 patients with etanercept), and 46
      patients treated with non-steroidal anti-inflammatory drugs and/or other disease
      modifying anti-rheumatic drugs. The C-reactive protein (CRP), erythrocyte
      sedimentation rate (ESR), hemoglobin (HGB), hematocrit (HCT) counts, and BASDAI
      scores were compared before starting therapy and at 52 weeks. There was no
      statistically significant difference between patients about demographical data
      (age, sex) and disease age (p > 0.05 for all). Significant difference was
      determined between HGB, HCT, CRP, ESR, and BASDAI values before and after therapy
      (for infliximab p: 0.001; 0.000; 0.000; 0.000; 0.000, respectively, and for
      adalimumab p: 0.017; 0.03; 0.001; 0.002; 0.000, respectively). In etanercept
      group, there was no significant difference in HGB values, when compared with
      before starting therapy and at 52 weeks (p > 0.05). In the group of treated with
      non-biological agents, ESR values and BASDAI scores showed distinctive
      improvement after 52 weeks of therapy, but was not a significant difference in
      hemoglobin and hematocrit values. CONCLUSION: Anti-TNF-alpha therapy with
      monoclonal antibodies (adalimumab and infliximab) did not only suppress disease
      activity but also provided a significant improvement in HGB levels. In the groups
      of treated with a TNF-alpha receptor antagonist (ETA) and non-biological agents,
      disease activity was suppressed, but there was not founded significant
      improvement in HGB levels after 52 weeks. Different outcomes of anti-TNF agents
      may be associated with their different effect mechanisms.

PMID- 23143666
TI  - Survivin in adrenocortical tumors - pathophysiological implications and
      therapeutic potential.
AB  - Treatment options for adrenocortical carcinoma (ACC) are very limited. In other
      solid tumors, small vaccination trials targeting the anti-apoptotic molecule
      survivin suggested immunological and clinical benefit in selected patients.
      Therefore, we investigated whether survivin might be a suitable target for
      immunotherapy in ACC. Survivin mRNA and protein expression was assessed in
      adrenal tissue specimens [by real-time-PCR in 29 ACC, 24 adrenocortical adenomas
      (ACA) and 12 normal adrenal glands; by immunohistochemistry in 167 ACCs, 15 ACA,
      and 5 normal adrenal glands]. Expression was correlated with clinical outcome
      using Kaplan-Meier and Cox regression analyses. The anti-apoptotic role of
      survivin was investigated in the SW13 ACC cell line using survivin siRNA. The
      presence of spontaneous survivin specific T-cells in peripheral blood was
      assessed by FACS dextramere staining in 29 ACC patients in comparison to healthy
      controls. Survivin mRNA in ACC was significantly overexpressed when compared with
      ACA or normal adrenal glands. Immunohistochemistry confirmed survivin protein
      expression in 97% of the ACCs. In 83% of samples, staining was moderate or high
      and clinical outcome in this subgroup showed a trend towards poorer prognosis
      [hazard ratio for death 2.28 (95% CI 0.99-5.28); p=0.053]. Survivin knockdown in
      SW-13 cell significantly increased the rate of apoptosis. Finally, spontaneous
      survivin-reactive T cells were detectable in 3 of 29 ACC patients. In conclusion,
      our data suggest that survivin could play an important role in the anti-apoptotic
      mechanisms in ACC and provide first hints that targeting survivin might be an
      interesting new therapeutic approach in this rare disease.

PMID- 23143667
TI  - Abstracts of the Collaboration in Cancer Drug Trials, 2012 Chabner Colloquium.
      November 5-6, 2012. Boston, Massachusetts, USA.

PMID- 23143669
TI  - Novel treatments for epistaxis in hereditary hemorrhagic telangiectasia: a
      systematic review of the clinical experience with thalidomide.

PMID- 23143668
TI  - Impact of renal function on clopidogrel-induced antiplatelet effects in coronary
      artery disease patients without diabetes mellitus.
AB  - Diabetes mellitus (DM) is the most important predictor of chronic kidney disease
      (CKD), and pharmacodynamic (PD) studies have shown that DM patients with impaired
      renal function are characterized by reduced clopidogrel response. However, post
      hoc PD studies conducted in unselected cohorts, composed of both DM and non-DM
      patients, have reached controversial findings on the effects of CKD on
      clopidogrel response, likely attributed to patient heterogeneity. The impact of
      renal function on clopidogrel response in non-DM patients remains unexplored and
      represented the aim of this prospective investigation. We conducted a prospective
      PD investigation in non-DM patients with and without CKD defined as an estimated
      glomerular filtration rate (eGFR) below or above 60 mL/min, respectively. All
      patients had known coronary artery disease and were on maintenance aspirin
      therapy. PD assessments were assessed at baseline and 2 and 24 h after a 600 mg
      loading dose of clopidogrel. PD assays included light transmission aggregometry
      (LTA) using 5 and 20 MUmol ADP with and without PGE1 and flow cytometric
      assessment of the phosphorylation status of the vasodilator-stimulated
      phosphoprotein (VASP) to determine the platelet reactivity index. A total of 60
      patients were studied (n = 30 eGFR >=60 mL/min; n = 30 eGFR <60 mL/min). At
      baseline there were no differences between groups. Following clopidogrel loading
      dose administration, levels of on-treatment platelet reactivity were similar
      between groups at 2 and 24 h as measured with LTA and VASP. Accordingly, there
      were no differences in rates of high on-treatment platelet reactivity between
      groups. In non-DM patients with CAD, the presence of impaired renal function is
      not associated with differences in clopidogrel-induced antiplatelet effects
      compared with patients with preserved renal function.

PMID- 23143670
TI  - Exchange-coupled oxygen- and sulfur-bridged cyclopentadienyl-manganese(II) cages.
AB  - The trimetallic complex [{CpMn(MU-OSiPh3)2}2Mn] (1) and the heterocubane
      [CpMn(MU3-SSiPh3)]4 (2) are formed by deprotonation of Ph3SiQH (Q = O, S) by
      manganocene, or by transmetallation of manganocene by Ph3SiQLi. The Mn(II)
      centres in 1 and 2 are antiferromagnetically coupled, with J = -4.4 and -3.0 cm(
      1) in 1 and 2, respectively (-2J formalism).

PMID- 23143671
TI  - Identification of subtypes of refractory asthma in Korean patients by cluster
      analysis.
AB  - BACKGROUND: Refractory asthma, a subtype of asthma with uncontrolled symptoms
      despite antiasthma medications, is a heterogeneous syndrome with variable
      clinical features, presumably different etiologies, and pathophysiological
      mechanisms. The heterogeneity of refractory asthma, however, is poorly
      understood. We aimed to characterize refractory asthma and to improve our
      understanding of the heterogeneity of refractory asthma patients. METHODS: We
      identified refractory asthma patients (n = 96) as defined by the American
      Thoracic Society's criteria from a cohort of Korean asthma patients (n = 2,187).
      Then, cluster analysis was conducted to classify subtypes of refractory asthma.
      RESULTS: Among the study group, 4.4 % (n = 96) of all asthma patients had
      refractory asthma. Cluster analysis identified four distinct groups of refractory
      asthma. Age at onset was younger in clusters 1 and 2 than in clusters 3 and 4.
      Patients in cluster 1 had the most well-preserved pulmonary function; patients in
      cluster 2 had a female predominance and the most severe airway obstruction;
      patients in cluster 3 were mostly female and had the most enhanced bronchial
      hyperresponsiveness; and patients in cluster 4 were most male and tended to be
      cigarette smokers. CONCLUSIONS: The current results suggest that refractory
      asthma is a heterogeneous syndrome and could be classified into four subtypes.
      Underlying pathogenesis and therapeutic approaches may differ for the different
      subtypes and further research is needed.

PMID- 23143672
TI  - Electronic health record-based patient identification and individualized mailed
      outreach for primary cardiovascular disease prevention: a cluster randomized
      trial.
AB  - BACKGROUND: Many individuals at higher risk for cardiovascular disease (CVD) do
      not receive recommended treatments. Prior interventions using personalized risk
      information to promote prevention did not test clinic-wide effectiveness.
      OBJECTIVE AND DESIGN: To perform a 9-month cluster-randomized trial, comparing a
      strategy of electronic health record-based identification of patients with
      increased CVD risk and individualized mailed outreach to usual care.
      PARTICIPANTS: Patients of participating physicians with a Framingham Risk Score
      of at least 5 %, low-density lipoprotein (LDL)-cholesterol level above guideline
      threshold for drug treatment, and not prescribed a lipid-lowering medication were
      included in the intention-to-treat analysis. INTERVENTION: Patients of physicians
      randomized to the intervention group were mailed individualized CVD risk messages
      that described benefits of using a statin (and controlling hypertension or
      quitting smoking when relevant). MAIN MEASURES: The primary outcome was
      occurrence of a LDL-cholesterol level, repeated in routine practice, that was at
      least 30 mg/dl lower than prior. A secondary outcome was lipid-lowering drug
      prescribing. Clinicaltrials.gov identifier: NCT01286311. KEY RESULTS: Fourteen
      physicians with 218 patients were randomized to intervention, and 15 physicians
      with 217 patients to control. The mean patient age was 60.7 years and 77% were
      male. There was no difference in the primary outcome (11.0 % vs. 11.1 %, OR 0.99,
      95 % CI 0.56-1.74, P = 0.96), but intervention group patients were twice as
      likely to receive a prescription for lipid-lowering medication (11.9 %, vs. 6.0
      %, OR 2.13, 95 % CI 1.05-4.32, p = 0.038). In post hoc analysis with extended
      follow-up to 18 months, the primary outcome occurred more often in the
      intervention group (22.5 % vs. 16.1 %, OR 1.59, 95 % CI 1.05-2.41, P = 0.029).
      CONCLUSIONS: In this effectiveness trial, individualized mailed CVD risk messages
      increased the frequency of new lipid-lowering drug prescriptions, but we observed
      no difference in proportions lowering LDL-cholesterol after 9 months. With longer
      follow-up, the intervention's effect on LDL-cholesterol levels was apparent.

PMID- 23143673
TI  - Recent advances in the biology of germ cell tumors: implications for the
      diagnosis and treatment.
AB  - Testicular germ cell tumors (TGCT), are the most frequent solid malignant tumors
      in men 20-40 yr of age, and the most frequent cause of death from solid tumors in
      this age group. TGCT can be subdivided into seminoma and nonseminoma germ cell
      tumors (NSGCT), including embryonal cell carcinoma, choriocarcinoma, yolk sac
      tumor, and teratoma. Seminomas and NSGCT do not only present distinctive clinical
      features, but they also show significant differences as far as therapy and
      prognosis are concerned. Many novel markers have given further advantages to
      discriminate between histological subgroups. In addition, therapeutic approaches
      for the treatment of TGCT have been proposed: humanized antibodies against
      receptors/surface molecules on cancer cells, inhibitors of serine-threonine, and
      tyrosine kinases, and others. The review will focus on the recent advances in the
      research of molecular alterations identified in TGCT and on novel targeted anti
      neoplastic strategies that might help to treat chemotherapy-resistant TGCT.

PMID- 23143675
TI  - Spatiotemporal pattern of rod degeneration in the S334ter-line-3 rat model of
      retinitis pigmentosa.
AB  - We have recently described the surviving cones and Muller-glia process remodeling
      in retinitis pigmentosa (RP) and shown that rod degeneration triggers the
      reorganization of the cone mosaic into an orderly array of rings. Within these
      rings, remodeled Muller-glia processes envelope cones. Here, we report the
      spatiotemporal pattern of healthy rods, their relationship with dying rods and
      the way that rod death stimulates the modification of cone spatial-distribution
      patterns and Muller-glia processes in the S334ter-line-3 rat, a transgenic model
      expressing a rhodopsin mutation that causes RP. The spatial patterns of rods,
      cones, microglial and Muller cells were labeled by immunocytochemistry with cell
      type-specific markers at various stages of deveopment in rat whole-mount retinas.
      Spatial patterns of dying cells were examined by TUNEL staining. The S334ter rod
      mosaic began to develop small holes around postnatal day 10. These hot-spots of
      cell death progressively increased in size, leaving larger rod-less holes behind.
      The holes were temporarily occupied by active microglial cells, before being
      replaced by remodeled Muller-cell processes. Our data suggest that the hot spots
      of rod death create holes in the rod mosaic early in retinal degeneration and
      that the resulting pattern triggers the modification of the spatial-distribution
      patterns of cones and glia cells.

PMID- 23143674
TI  - Using chimeric mice with humanized livers to predict human drug metabolism and a
      drug-drug interaction.
AB  - Interspecies differences in drug metabolism have made it difficult to use
      preclinical animal testing data to predict the drug metabolites or potential drug
      drug interactions (DDIs) that will occur in humans. Although chimeric mice with
      humanized livers can produce known human metabolites for test substrates, we do
      not know whether chimeric mice can be used to prospectively predict human drug
      metabolism or a possible DDI. Therefore, we investigated whether they could
      provide a more predictive assessment for clemizole, a drug in clinical
      development for the treatment of hepatitis C virus (HCV) infection. Our results
      demonstrate, for the first time, that analyses performed in chimeric mice can
      correctly identify the predominant human drug metabolite before human testing.
      The differences in the rodent and human pathways for clemizole metabolism were of
      importance, because the predominant human metabolite was found to have
      synergistic anti-HCV activity. Moreover, studies in chimeric mice also correctly
      predicted that a DDI would occur in humans when clemizole was coadministered with
      a CYP3A4 inhibitor. These results demonstrate that using chimeric mice can
      improve the quality of preclinical drug assessment.

PMID- 23143676
TI  - Effects of transplanted bone-marrow-derived mesenchymal stem cells in animal
      models of acute hepatitis.
AB  - Our aim was to evaluate the therapeutic effects of bone-marrow-derived
      mesenchymal stem cells (BMMSCs) on ConA-induced hepatitis and to elucidate the
      possible mechanism involved. MSCs were isolated from bone marrow and their
      characteristics and anti-apoptotic effects on the L02 cell line were analyzed.
      The effect of intravenous infusion of BMMSCs on liver damage was also tested.
      Furthermore, the recruitment of donor BMMSCs to the liver of recipient animals
      and their effects on the activity of intrahepatic natural killer T (NKT) cells
      were investigated. BMMSCs ameliorated liver damage in a time- and dose-dependent
      manner. Donor BMMSCs were detected in the livers of recipient animals, suggesting
      that tissue damage stimulated the migration of BMMSCs. Transplanted BMMSCs also
      suppressed the activity of intrahepatic NKT cells, not only in the liver but
      throughout the body. The general infusion of BMMSCS ameliorated immunoregulatory
      activities by the suppression of intrahepatic NKT cells.

PMID- 23143677
TI  - Computational design of a CNT carrier for a high affinity bispecific anti-HER2
      antibody based on trastuzumab and pertuzumab Fabs.
AB  - This is a preliminary cross multidisciplinary theoretical-computational approach
      for the design of a drug delivery system based on immunoconjugated carbon
      nanotube against HER2- overexpressing cancer cells. This drug delivery system
      allows the release of an encapsulated cytotoxic cocktail in a controlled manner
      under pulsed radio frequency (RF) irradiation. Our effort is focused on the
      computational aided design of a high affinity bispecific anti-HER2 antibody and
      an opening mechanism of the carbon nanotube (CNT) based cytotoxic carrier for
      controlling multiple drug release. We study the main interactions between the
      antibody and the antigen by a computational scanning mutagenesis approach of
      trastuzumab and pertuzumab fragment antigen binding (Fab) structures in order to
      enhance their binding affinity. Then, each Fab fragments is joined by a
      polypeptide linker which should be stable enough to avoid the "open form" of
      antibody. On the other hand, we also conjugate the engineered antibody to
      functionalized CNTs (f-CNTs), which encapsulate the inhibitors of the
      HER2/PI3K/Akt/mTOR signaling pathway. We take advantage of the fact that f-CNT
      converts the RF radiation absorption into heat release. A pulsed laser at 13.45
      MHz increments the temperature around 40  degrees C for triggering the nano-caps
      destabilization, which allows the switching of the opening mechanism of the drug
      carrier. Nano-caps will be a dual pH/temperature responsive in order to take
      advantage of lysosome characteristic (acidic pH) and heat release from the
      carrier. Nano-caps are functionalized with organic amide moieties, which
      hydrolyze quickly at an acidic pH into primary amines, and protonated amines
      generate repulsion interactions with other charged species, which trigger the
      cytotoxics release.

PMID- 23143678
TI  - The role of fluorine in stabilizing the bioactive conformation of dihydroorotate
      dehydrogenase inhibitors.
AB  - Dihydroorotate dehydrogenase (DHODH) is an important drug target due to its
      prominent role in pyrimidine biosynthesis. Leflunomide and brequinar are two well
      known DHODH inhibitors, which bind to the enzyme in the same pocket with
      different binding modes. We have recently realized a series of new inhibitors
      based on the 4-hydroxy-1,2,5-oxadiazole ring, whose activity profile was found to
      be closely dependent on the degree of fluorine substitution at the phenyl ring
      adjacent to the oxadiazole moiety; a positive influence of fluorine on the DHODH
      inhibitory potency was observed previously [Baumgartner et al. (2006) J Med Chem
      49:1239-1247]. Potential energy surface scans showed that fluorine plays an
      important role in stabilizing the bioactive conformations; additionally, fluorine
      influences the balance between leflunomide-like and brequinar-like binding modes.
      These findings may serve as a guide to design more potent DHODH inhibitors.

PMID- 23143679
TI  - CCL2 is critical for immunosuppression to promote cancer metastasis.
AB  - We previously found that cancer metastasis is accelerated by immunosuppression
      during Snail-induced epithelial-to-mesenchymal transition (EMT). However, the
      molecular mechanism still remained unclear. Here, we demonstrate that CCL2 is a
      critical determinant for both tumor metastasis and immunosuppression induced by
      Snail(+) tumor cells. CCL2 is significantly upregulated in various human tumor
      cells accompanied by Snail expression induced by snail transduction or TGFbeta
      treatment. The Snail(+) tumor-derived CCL2 amplifies EMT events in other cells
      including Snail(-) tumor cells and epithelial cells within tumor
      microenvironment. CCL2 secondarily induces Lipocalin 2 (LCN2) in the Snail(+)
      tumor cells in an autocrine manner. CCL2 and LCN2 cooperatively generate
      immunoregulatory dendritic cells (DCreg) having suppressive activity accompanied
      by lowered expression of costimulatory molecules such as HLA-DR but increased
      expression of immunosuppressive molecules such as PD-L1 in human PBMCs. The
      CCL2/LCN2-induced DCreg cells subsequently induce immunosuppressive
      CD4(+)FOXP3(+) Treg cells, and finally impair tumor-specific CTL induction. In
      murine established tumor model, however, CCL2 blockade utilizing the specific
      siRNA or neutralizing mAb significantly inhibits Snail(+) tumor growth and
      metastasis following systemic induction of anti-tumor immune responses in host.
      These results suggest that CCL2 is more than a chemoattractant factor that is the
      significant effector molecule responsible for immune evasion of Snail(+) tumor
      cells. CCL2 would be an attractive target for treatment to eliminate cancer cells
      via amelioration of tumor metastasis and immunosuppression.

PMID- 23143680
TI  - Smad interacting protein 1 (SIP1) is associated with peritoneal carcinomatosis in
      intestinal type gastric cancer.
AB  - Smad interacting protein 1 (SIP1) is an epithelial-mesenchymal transition (EMT)
      inducible gene that plays a key role in tumor progression in various cancers.
      This study seeks to clarify the clinical and biological significance of SIP1
      expression, especially in intestinal type gastric cancer. We analyzed the mRNA
      levels of SIP1 and other EMT regulators by real-time reverse transcription PCR in
      gastric tissue samples of 134 gastric cancer patients, and in five gastric cancer
      cell lines. SIP1 gene knockdown by siRNA transfection was performed to evaluate
      SIP1 function in gastric cancer cells. Expression of the SIP1 gene was
      significantly higher in cancerous tissue than in adjacent normal mucosa. Although
      the mRNA expression of the other EMT regulators tested (Snail, Slug, and Twist)
      was not correlated with clinicopathological factors, increased SIP1 expression
      was an independent prognostic factor and an independent risk factor for
      peritoneal dissemination. In addition, SIP1 expression was significantly positive
      and correlated with vimentin expression. For intestinal type gastric cancer in
      particular, elevated SIP1 expression was significantly correlated with peritoneal
      dissemination and poor prognosis (p < 0.05). In vitro, cell proliferation,
      migration, invasion, and resistance to anoikis were significantly inhibited in
      SIP1 siRNA-transfected MKN7 cells compared to control siRNA. SIP1 appears to play
      an important role in progression to peritoneal carcinomatosis and may be a
      therapeutic target for patients with intestinal type gastric cancer.

PMID- 23143681
TI  - Size discrimination in rat and mouse gastric emptying.
AB  - OBJECTIVES: To investigate the relationship between particle size and gastric
      emptying in rodents using radiolabeled insoluble polymethyl methacrylate (PMMA)
      microcapsules/beads. METHODS: PMMA microcapsules (50-500 um) and beads (0.5-3 mm)
      loaded with technetium-99 m diethylenetriamine pentaacetic acid ((99m) Tc-DTPA)
      were administered to ICR mice or Sprague Dawley (SD) rats by oral gavage. Gamma
      scintiscans were acquired initially following administration and then at hourly
      intervals to 4 hours. RESULTS: Scintiscans revealed that the smallest PMMA
      microcapsules (50-100 um) or beads (0.5-1 mm) were impeded in the stomach and
      emptied slower than large particles in both rodent species. In mice, no
      significant difference in gastric emptying was found with microcapsules between
      100 and 300 um in diameter (p = 0.25) and particles more than 300 um could not be
      administered. In rats, capsules containing 0.5-3 mm beads were stuck to the
      esophagus (up to 1 hour), this was a limitation of dosing beads of this size
      because they cannot be suspended in a liquid media for oral gavage purposes.
      Beads with diameters of 2-3 mm stayed in the stomach for up to 4 hours.
      CONCLUSIONS: The cut-off emptying size in ICR mice could not be determined, due
      to the limitation of current available dosing methods. The cut-off emptying size
      in SD rats was between 1.5 and 2 mm. Therefore, particles with a diameter greater
      than 2 mm should not be used for gastric emptying studies of intact particles in
      SD rats, as their emptying is retarded in the stomach.

PMID- 23143682
TI  - A 20pi-electron heteroporphyrin containing a thienopyrrole unit.

PMID- 23143683
TI  - Candida albicans induces arginine biosynthetic genes in response to host-derived
      reactive oxygen species.
AB  - The interaction of Candida albicans with phagocytes of the host's innate immune
      system is highly dynamic, and its outcome directly impacts the progression of
      infection. While the switch to hyphal growth within the macrophage is the most
      obvious physiological response, much of the genetic response reflects nutrient
      starvation: translational repression and induction of alternative carbon
      metabolism. Changes in amino acid metabolism are not seen, with the striking
      exception of arginine biosynthesis, which is upregulated in its entirety during
      coculture with macrophages. Using single-cell reporters, we showed here that
      arginine biosynthetic genes are induced specifically in phagocytosed cells. This
      induction is lower in magnitude than during arginine starvation in vitro and is
      driven not by an arginine deficiency within the phagocyte but instead by exposure
      to reactive oxygen species (ROS). Curiously, these genes are induced in a narrow
      window of sublethal ROS concentrations. C. albicans cells phagocytosed by primary
      macrophages deficient in the gp91(phox) subunit of the phagocyte oxidase do not
      express the ARG pathway, indicating that the induction is dependent on the
      phagocyte oxidative burst. C. albicans arg pathway mutants are retarded in germ
      tube and hypha formation within macrophages but are not notably more sensitive to
      ROS. We also find that the ARG pathway is regulated not by the general amino acid
      control response but by transcriptional regulators similar to the Saccharomyces
      cerevisiae ArgR complex. In summary, phagocytosis induces this single amino acid
      biosynthetic pathway in an ROS-dependent manner.

PMID- 23143684
TI  - Identification of the mating-type (MAT) locus that controls sexual reproduction
      of Blastomyces dermatitidis.
AB  - Blastomyces dermatitidis is a dimorphic fungal pathogen that primarily causes
      blastomycosis in the midwestern and northern United States and Canada. While the
      genes controlling sexual development have been known for a long time, the genes
      controlling sexual reproduction of B. dermatitidis (teleomorph, Ajellomyces
      dermatitidis) are unknown. We identified the mating-type (MAT) locus in the B.
      dermatitidis genome by comparative genomic approaches. The B. dermatitidis MAT
      locus resembles those of other dimorphic fungi, containing either an alpha-box
      (MAT1-1) or an HMG domain (MAT1-2) gene linked to the APN2, SLA2, and COX13
      genes. However, in some strains of B. dermatitidis, the MAT locus harbors
      transposable elements (TEs) that make it unusually large compared to the MAT
      locus of other dimorphic fungi. Based on the MAT locus sequences of B.
      dermatitidis, we designed specific primers for PCR determination of the mating
      type. Two B. dermatitidis isolates of opposite mating types were cocultured on
      mating medium. Immature sexual structures were observed starting at 3 weeks of
      coculture, with coiled-hyphae-containing cleistothecia developing over the next 3
      to 6 weeks. Genetic recombination was detected in potential progeny by mating
      type determination, PCR-restriction fragment length polymorphism (PCR-RFLP), and
      random amplification of polymorphic DNA (RAPD) analyses, suggesting that a
      meiotic sexual cycle might have been completed. The F1 progeny were sexually
      fertile when tested with strains of the opposite mating type. Our studies provide
      a model for the evolution of the MAT locus in the dimorphic and closely related
      fungi and open the door to classic genetic analysis and studies on the possible
      roles of mating and mating type in infection and virulence.

PMID- 23143685
TI  - Improved gene ontology annotation for biofilm formation, filamentous growth, and
      phenotypic switching in Candida albicans.
AB  - The opportunistic fungal pathogen Candida albicans is a significant medical
      threat, especially for immunocompromised patients. Experimental research has
      focused on specific areas of C. albicans biology, with the goal of understanding
      the multiple factors that contribute to its pathogenic potential. Some of these
      factors include cell adhesion, invasive or filamentous growth, and the formation
      of drug-resistant biofilms. The Gene Ontology (GO) (www.geneontology.org) is a
      standardized vocabulary that the Candida Genome Database (CGD)
      (www.candidagenome.org) and other groups use to describe the functions of gene
      products. To improve the breadth and accuracy of pathogenicity-related gene
      product descriptions and to facilitate the description of as yet uncharacterized
      but potentially pathogenicity-related genes in Candida species, CGD undertook a
      three-part project: first, the addition of terms to the biological process branch
      of the GO to improve the description of fungus-related processes; second, manual
      recuration of gene product annotations in CGD to use the improved GO vocabulary;
      and third, computational ortholog-based transfer of GO annotations from
      experimentally characterized gene products, using these new terms, to
      uncharacterized orthologs in other Candida species. Through genome annotation and
      analysis, we identified candidate pathogenicity genes in seven non-C. albicans
      Candida species and in one additional C. albicans strain, WO-1. We also defined a
      set of C. albicans genes at the intersection of biofilm formation, filamentous
      growth, pathogenesis, and phenotypic switching of this opportunistic fungal
      pathogen, which provides a compelling list of candidates for further
      experimentation.

PMID- 23143686
TI  - Platelets with a W127X mutation in GPIX express sufficient residual amounts of
      GPIbalpha to support adhesion to von Willebrand factor and collagen.
AB  - Bernard-Soulier syndrome (BSS) is an inherited bleeding disorder caused by a
      defect in the platelet glycoprotein (GP) Ib/IX complex. The GPIX W127X mutation
      is the most common genetic defect in Japanese patients with BSS, which is often
      misdiagnosed as immune thrombocytopenic purpura, presumably due to residual
      expression of GPIbalpha. Neither the mechanism by which this mutation leads to a
      mild bleeding diathesis, nor whether functional GPIbalpha is expressed on
      platelet surfaces is known. We investigated GPIbalpha expression and function in
      platelets with a GPIX W127X mutation (GPIXW127X). GPIbalpha complexed with
      GPIbbeta by disulfide bonding was expressed on GPIXW127X platelets and stable CHO
      K1 cells lacking GPIX but expressing GPIbalpha and GPIbbeta. Expression of
      GPIbalpha/beta on GPIXW127X platelets was sufficient to support adhesion to
      immobilized von Willebrand factor and type III collagen and ristocetin-induced
      platelet agglutination. A residual amount of functional GPIbalpha/beta heteromer
      expressed on GPIXW127X platelets partially compensates for the absence of the
      GPIb/IX complex. This may account for the mild bleeding phenotype of the BSS
      variant characterized by a non-sense mutation in GPIX.

PMID- 23143687
TI  - Treatment of severe acute graft-versus-host disease with mesenchymal stromal
      cells: a comparison with non-MSC treated patients.

PMID- 23143688
TI  - Differences in hemodynamic parameters and exercise capacity between patients with
      pulmonary arterial hypertension and chronic heart failure.
AB  - INTRODUCTION: Although pulmonary arterial hypertension (PAH) and chronic heart
      failure (CHF) lead to exercise limitation, their pathophysiology is different.
      Our objective was to evaluate, using right heart catheterization and
      cardiopulmonary exercise testing, the difference in hemodynamic parameters and
      exercise capacity between PAH and CHF, which have the same subjective symptoms.
      METHODS: We studied 20 PAH (mean pulmonary artery pressure: 36 +/- 10 mmHg, all .
      25 mmHg) and 20 CHF (ejection fraction: 35 +/- 10%, all < 40%) patients who
      underwent both cardiopulmonary exercise testing and right heart catheterization.
      All patients were in New York Heart Association functional class II or III.
      RESULTS: Peak oxygen uptake (VO(2)) was lower for PAH patients than for CHF
      patients (11.7 +/- 3.2 mL.kg(-1).min(-1) vs 14.5 +/- 4.6 mL.kg(-1).min(-1), P =
      .03), while the slope of ventilation to carbon dioxide production ratio
      (VE/VCO(2)) was higher for PAH patients than for CHF patients (41.0 +/- 12.7 vs
      28.0 +/- 9.0, P = .001), despite the similarity in their New York Heart
      Association functional class. Peak VO(2) and VE/VCO(2) correlated with cardiac
      index for both groups. An important finding was that peak VO(2) correlated with
      pulmonary vascular resistance for PAH patients (r = 20.46, P = .04) but not for
      CHF patients (r = 0.33, P = .15). Furthermore, peak VO(2) correlated with
      pulmonary capillary wedge pressure for CHF patients (r = 20.47, P = .03) but not
      for PAH patients (r = 0.17, P = .47), while the VE/VCO(2) slope correlated with
      pulmonary capillary wedge pressure (r = 0.67, P = .002) but not with pulmonary
      vascular resistance (r = 0.12, P = .63) for CHF patients. CONCLUSION: Peak VO(2)
      and VE/VCO(2) slope were worse for PAH patients than for CHF patients despite the
      similar subjective symptoms. This difference might be explained by an altered
      hemodynamic status.

PMID- 23143689
TI  - Pharmacist intervention in cardiac rehabilitation: a randomized controlled trial.
AB  - PURPOSE: We aimed to determine to what extent a telephone-based pharmacist
      intervention would (a) be utilized by individuals not attending a traditional
      cardiac rehabilitation (CR) program and (b) facilitate adherence to
      cardiovascular medications. METHODS: We conducted a randomized, controlled open
      label trial among patients eligible for CR in Saskatoon, Canada. Patients were
      invited to participate in telephone-based CR, regardless of participation in the
      formal program. Subjects in the intervention group were assessed by the CR
      pharmacist and received education and counseling on medication adherence. The
      primary endpoint was adherence to cardiovascular medication assessed by
      electronic filling records over a minimum of 6 months. Mean adherence was
      expected to reach 70% during the followup period. RESULTS: Patient recruitment
      was halted early because of low enrollment. Of the 95 patients randomized, 90%
      had also registered in the traditional CR program. During the followup period,
      129 telephone interactions were performed (median, 2 calls), with every subject
      taking part in at least 1 interaction. Over the study period, the mean adherence
      to all recently initiated cardiovascular medications combined was 88.8% in the
      intervention group and 89.9% in the usual care group (P = .73). CONCLUSIONS:
      Participation in traditional CR programs does not appear to be influenced by the
      availability of telephone-based education and support. Furthermore, the high rate
      of adherence among the control group may suggest that CR programs are attracting
      "healthy adherers" who volunteer for such programs, while missing those with the
      greatest need for health care system resources.

PMID- 23143691
TI  - Efficiency of neural network-based combinatorial model predicting optimal culture
      conditions for maximum biomass yields in hairy root cultures.
AB  - KEY MESSAGE : ANN-based combinatorial model is proposed and its efficiency is
      assessed for the prediction of optimal culture conditions to achieve maximum
      productivity in a bioprocess in terms of high biomass. A neural network approach
      is utilized in combination with Hidden Markov concept to assess the optimal
      values of different environmental factors that result in maximum biomass
      productivity of cultured tissues after definite culture duration. Five hidden
      Markov models (HMMs) were derived for five test culture conditions, i.e. pH of
      liquid growth medium, volume of medium per culture vessel, sucrose concentration
      (%w/v) in growth medium, nitrate concentration (g/l) in the medium and finally
      the density of initial inoculum (g fresh weight) per culture vessel and their
      corresponding fresh weight biomass. The artificial neural network (ANN) model was
      represented as the function of these five Markov models, and the overall
      simulation of fresh weight biomass was done with this combinatorial ANN-HMM. The
      empirical results of Rauwolfia serpentina hairy roots were taken as model and
      compared with simulated results obtained from pure ANN and ANN-HMMs. The
      stochastic testing and Cronbach's alpha-value of pure and combinatorial model
      revealed more internal consistency and skewed character (0.4635) in histogram of
      ANN-HMM compared to pure ANN (0.3804). The simulated results for optimal
      conditions of maximum fresh weight production obtained from ANN-HMM and ANN model
      closely resemble the experimentally optimized culture conditions based on which
      highest fresh weight was obtained. However, only 2.99 % deviation from the
      experimental values could be observed in the values obtained from combinatorial
      model when compared to the pure ANN model (5.44 %). This comparison showed 45 %
      better potential of combinatorial model for the prediction of optimal culture
      conditions for the best growth of hairy root cultures.

PMID- 23143693
TI  - Expression of UDP-glucuronosyltransferase 1A in bladder cancer: association with
      prognosis and regulation by estrogen.
AB  - Although UDP-glucuronosyltransferase 1A (UGT1A) plays an important role in
      preventing bladder cancer initiation by detoxifying carcinogenic compounds, its
      contribution to bladder cancer progression is poorly understood. We
      immunohistochemically stained for UGT1A in bladder specimens. UGT1A was positive
      in 130/145 (90%; 28 [19%] weak, 53 [37%] moderate, and 49 [34%] strong)
      urothelial neoplasms, which was significantly weaker than in matched non
      neoplastic urothelial tissues (100/101 [99%]; 2 [2%] weak, 17 [17%] moderate, and
      81 [80%] strong). Fifty (98%) of 51 low-grade/79 (99%) of 80 non-muscle-invasive
      tumors were immunoreactive to UGT1A, whereas 80 (85%) of 94 high-grade/51 (78%)
      of 65 muscle-invasive tumors were UGT1A-positive. Kaplan-Meier analysis showed
      strong associations between lower UGT1A expression versus the risk of recurrence
      in high-grade non-muscle-invasive tumors (P = 0.038) or disease-specific
      mortality in muscle-invasive tumors (P = 0.016). Multivariate analysis further
      revealed UGT1A loss as an independent prognosticator for disease-specific
      mortality in patients with muscle-invasive tumor (P = 0.010). Additionally, the
      expression of UGT1A was positively and negatively correlated with those of
      estrogen receptor-alpha and estrogen receptor-beta, respectively. We then
      assessed UGT1A/Ugt1a levels in human cell lines/mouse tissues. 17beta-Estradiol
      increased and decreased UGT1A expression in normal urothelium and bladder cancer
      lines, respectively, and an anti-estrogen abolished these effects. Ovariectomy in
      mice resulted in down-regulation of Ugt1a subtypes. These results suggest the
      involvement of UGT1A in not only bladder carcinogenesis but tumor progression.
      Moreover, UGT1A is likely regulated by estrogens in non-neoplastic urothelium
      versus bladder tumor in opposite manners, which could be underlying mechanisms of
      gender-specific differences in bladder cancer incidence and progression.

PMID- 23143694
TI  - Combined blockade of TIM-3 and TIM-4 augments cancer vaccine efficacy against
      established melanomas.
AB  - Cancer vaccines have been developed to instruct the endogenous immune responses
      to autologous tumors and to generate durable clinical responses. However, the
      therapeutic benefits of cancer vaccines remain insufficient due to the multiple
      immunosuppressive signals delivered by tumors. Thus, to improve the clinical
      efficacy of cancer immunotherapy, it is important to develop new modalities to
      overcome immunosuppressive tumor microenvironments and elicit effective antitumor
      immune responses. In this study, we show that novel monoclonal antibodies (mAbs)
      specifically targeting either T cell immunoglobulin mucin protein-3 (TIM-3) or T
      cell immunoglobulin mucin protein-4 (TIM-4) enhance the therapeutic effects of
      vaccination against established B16 murine melanomas. This is true for
      vaccination with irradiated B16 melanoma cells engineered to express the flt3
      ligand gene (FVAX). More importantly, combining anti-TIM-3 and anti-TIM-4 mAbs
      markedly increased vaccine-induced antitumor responses against established B16
      melanoma. TIM-3 blockade mainly stimulated antitumor effector activities via
      natural killer cell-dependent mechanisms, while CD8(+) T cells served as the main
      effectors induced by anti-TIM-4 mAb. Our findings reveal that therapeutic
      manipulation of TIM-3 and TIM-4 may provide a novel strategy for improving the
      clinical efficacy of cancer immunotherapy.

PMID- 23143695
TI  - The cardiovascular system in growth hormone excess and growth hormone deficiency.
AB  - The clinical conditions associated with GH excess and GH deficiency (GHD) are
      known to be associated with an increased risk for the cardiovascular morbidity
      and mortality, suggesting that either an excess or a deficiency in GH and/or IGF
      I is deleterious for cardiovascular system. In patients with acromegaly, chronic
      GH and IGF-I excess commonly causes a specific cardiomyopathy characterized by a
      concentric cardiac hypertrophy associated with diastolic dysfunction and, in
      later stages, with systolic dysfunction ending in heart failure if GH/IGF-I
      excess is not controlled. Abnormalities of cardiac rhythm and anomalies of
      cardiac valves can also occur. Moreover, the increased prevalence of
      cardiovascular risk factors, such as hypertension, diabetes mellitus, and insulin
      resistance, as well as dyslipidemia, confer an increased risk for vascular
      atherosclerosis. Successful control of the disease is accompanied by a decrease
      of the cardiac mass and improvement of cardiac function and an improvement in
      cardiovascular risk factors. In patients with hypopituitarism, GHD has been
      considered the under- lying factor of the increased mortality when appropriate
      standard replacement of the pituitary hormones deficiencies is given. Either
      childhood-onset or adulthood-onset GHD are characterized by a cluster of
      abnormalities associated with an increased cardiovascular risk, including altered
      body composition, unfavorable lipid profile, insulin resistance, endothelial
      dysfunction and vascular atherosclerosis, a decrease in cardiac mass together
      with an impairment of systolic function mainly after exercise. Treatment with
      recombinant GH in patients with GHD is followed by an improvement of the
      cardiovascular risk factors and an increase in cardiac mass together with an
      improvement in cardiac performance. In conclusion, acromegaly and GHD are
      associated with an increased risk for cardiovascular morbidity and mortality, but
      the control of GH/IGF-I secretion reverses cardiovascular abnormalities and
      restores the normal life expectancy.

PMID- 23143696
TI  - Regional cerebellar volume reflects static balance in elite female short-track
      speed skaters.
AB  - The cerebellum plays a critical role in balance control. Particularly, elite
      short-track speed skaters require fine postural control to keep a postural
      balance during high velocity movement across smooth ice. We investigated whether
      skating proficiency and gender have an effect on the volume of cerebellar
      subregions and static balance, using 3-dimensional magnetic resonance imaging
      volumetry. In addition, we further analyzed which subregions of the cerebellum
      correlates with the balance. The volumes of cerebellar subregions and static
      balance index were compared among 12 male and 11 female elite short-track speed
      skaters, and 11 male and 14 female healthy matched subjects. We found significant
      main effects of skating proficiency and gender on the volume of vermian lobule VI
      VII (declive, folium, and tuber), short-track speed skaters having greater volume
      than control and women revealing greater volume than men. Especially, in female
      athletic group, the volume of vermian lobule VI-VII significantly correlates with
      left static balance. In addition, men showed larger skating proficiency-related
      differences than women in the performance of static balance. The correlation
      between the volume of this region and static balance in female short-track speed
      skaters suggests that this region would plays a critical role in balance.

PMID- 23143697
TI  - Sex difference in strength and size ratios between reciprocal muscle groups in
      the lower leg.
AB  - This study compared strength and size of reciprocal muscle groups in the lower
      leg between sexes. 20 young men and 14 young women volunteered as subjects. Joint
      torques developed during isometric maximal voluntary plantar flexion (TQPF) and
      dorsiflexion (TQDF) were measured using a dynamometer. Muscle volumes of plantar
      flexors (MVPF) and dorsiflexors (MVDF) were determined by magnetic resonance
      imaging. In each of the muscle groups, joint torque was significantly correlated
      with muscle volume in young men and women (r=0.610-0.848) and the y-intercept of
      the regression line between them was not significantly different from zero. Based
      on these observations, the dependencies of muscle strength ratio on muscle size
      ratio between the plantar flexors and dorsiflexors were investigated using joint
      torque and muscle volume. The correlations between the MVPF per MVDF and the TQPF
      per TQDF were significant both in young men (r=0.608) and women (r=0.773),
      suggesting that strength ratio is strongly affected by size ratio between the
      plantar flexors and dorsiflexors in young men and women.

PMID- 23143698
TI  - Effects of footwear on impact forces and soft tissue vibrations during drop jumps
      and unanticipated drop landings.
AB  - The purpose of this study was to explore the footwear effects on impact forces
      and soft-tissue vibrations during landing. 12 male basketball players were
      instructed to perform drop jumps and unanticipated drop landings from 30 cm, 45
      cm, and 60 cm heights in basketball shoes (BS) and control shoes (CS). 3D
      kinematics, ground reaction force (GRF), and soft-tissue vibrations of the leg,
      and acceleration of the shoe heel counter were measured simultaneously. The
      results showed no significant shoe effect on the characteristics of the impact
      force nor on the resonance frequency and peak transmissibility of soft-tissue
      vibrations during the impact phase of the drop jump. For the unanticipated drop
      landings, however, the magnitude of both peak GRF and peak loading rate were
      significantly lower with BS compared to CS across all 3 heights (p<0.05);
      meanwhile BS showed a significant decrease in GRF frequency compared to CS at 45
      cm (p<0.05) and 60 cm (p<0.01) heights. Furthermore, the peak transmissibility in
      BS was significantly lower than that in CS for both the quadriceps and hamstrings
      during the 60 cm unanticipated drop landing (p<0.05). These findings provide
      preliminary evidence suggesting that if the neuromuscular system fails to prepare
      properly for an impact during landing, a shoe intervention may be an effective
      method for minimizing impact force and reducing soft tissue resonance.

PMID- 23143699
TI  - Arthroscopic treatment of glenohumeral instability in soccer goalkeepers.
AB  - The aim of this study was to report epidemiologic data and results of
      arthroscopic treatment of glenohumeral instability in soccer goalkeepers. We
      included 12 soccer goalkeepers with a mean age of 28.9 years (range 18-45 years)
      with acute or recurrent traumatic anterior instability who underwent an
      arthroscopic anatomic capsulolabral repair with bone anchors. Patients who
      underwent surgery within 4 weeks of the first episode of dislocation were
      classified as acute instability. The results were evaluated using the Rowe Scale
      and analyzed according to stability, range of motion and function. The mean
      follow-up was 3.8 years. The most common mechanism of injury (90% of the cases)
      was abduction, external rotation and extension. Associated injuries were present
      in 57.2% of recurrent cases and 20% of acute cases (p<0.293). Excellent or good
      results were observed in 80% of the cases of acute instability and in 57.2% of
      cases in the group with recurrent instability (p<0.586). From a total of 12
      soccer goalkeepers who underwent the arthroscopic capsulolabral repair, good or
      excellent results were obtained in 66.6% of cases of glenohumeral instability.
      Surgical arthroscopic repair was possible in all cases of acute or recurrent
      instability based on well-established inclusion criteria, i. e., with well
      defined exclusion criteria, such as HAGL lesion and significant glenohumeral bone
      loss, the arthroscopic capsulolabral repair can be carried out in soccer
      goalkeepers.

PMID- 23143700
TI  - Food restriction reverses the hyper-muscular phenotype and force generation
      capacity deficit of the myostatin null mouse.
AB  - Food restriction has a great impact on skeletal muscle mass by inducing muscle
      protein breakdown to provide substrates for energy production through
      gluconeogenesis. Genetic models of hyper-muscularity interfere with the normal
      balance between protein synthesis and breakdown which eventually results in
      extreme muscle growth. Mutations or deletions in the myostatin gene result in
      extreme muscle mass. Here we evaluated the impact of food restriction for a
      period of 5 weeks on skeletal muscle size (i. e., fibre cross-sectional area),
      fibre type composition and contractile properties (i. e., tetanic and specific
      force) in myostatin null mice. We found that this hyper-muscular model was more
      susceptible to catabolic processes than wild type mice. The mechanism of skeletal
      muscle mass loss was examined and our data shows that the myostatin null mice
      placed on a low calorie diet maintained the activity of molecules involved in
      protein synthesis and did not up-regulate the expression of genes pivotal in
      ubiquitin-mediated protein degradation. However, we did find an increase in the
      expression of genes associated with autophagy. Surprisingly, the reduction on
      muscle size was followed by improved tetanic and specific force in the null mice
      compared to wild type mice. These data provide evidence that food restriction may
      revert the hyper-muscular phenotype of the myostatin null mouse restoring muscle
      function.

PMID- 23143701
TI  - Lower limbs power and stiffness after whole-body vibration.
AB  - The interest in whole-body vibration (WBV) for the enhancement of neuromuscular
      performance has received considerable attention. However, scientific evidence
      supporting the optimal prescription of WBV settings is lacking. This study
      investigated the acute effect of WBV combining high frequency/high peak-to-peak
      displacement (HH) or low frequency/low peak-to-peak displacement (LL) vs. sham
      intervention (SHAM) on lower limb muscle power and stiffness. A total of 223
      volunteers were randomly assigned to either the HH, LL or SHAM group.
      Countermovement jump (CMJ) height, maximal and average power, maximal and average
      lower limbs stiffness obtained during a hopping test were recorded before and
      after the respective intervention. After the intervention, the HH group showed an
      increase of 4.64% in CMJ height (p<0.001) whereas the values of both the LL and
      SHAM groups did not change. In addition, maximal and average power of the lower
      limbs were significantly increased in all groups (p<0.001; 10.89% and 12.82%,
      respectively) while no effect on lower limbs stiffness was observed. Our data
      show that high frequency combined with high peak-to-peak displacement is the most
      optimal WBV setting for CMJ height enhancement. Further investigation should be
      undertaken to ascertain the effectiveness of WBV on lower limbs stiffness.

PMID- 23143702
TI  - A field-test battery for elite, young soccer players.
AB  - The validity and reliability of a battery of field-based performance tests was
      examined. The opinions of coaches, fitness professionals and players (n=170, 172
      and 101 respectively) on the importance of performance testing were established
      using a questionnaire. On 2 occasions, separated by 7 days, 80 elite, young
      soccer players (mean+/-SD [and range]: age 13.2+/-2.6 [8.9-19.1] years; stature
      1.59+/-0.18 m [1.32-1.91]; body mass 50.6+/-17.1 [26.5-88.7] kg) completed a
      battery of field-based tests comprised of heart rate response to a submaximal
      Multi-stage fitness test, 3 types of vertical jump, sprints over 10 and 20 m, and
      an agility test. Physical performance testing was considered important by coaches
      (97%), fitness professionals (94%) and players (83%). The systematic bias ratio
      and the random error components of the 95% ratio limits of agreement for the
      first and second tests, for the U9-U11 vs. U12-U14 vs. U15-U18 age groups, were
      [Systematic bias (*// ratio limits)]: Heart rate (Level 5): 0.983 (*// 1.044) vs.
      0.969 (*// 1.056) vs. 0.983 (*// 1.055); Rocket jump: 0998 (*// 1.112) vs. 0.999
      (*// 1.106) vs. 0.996 (*// 1.093); 10 m sprint: 0.997 (*// 1.038) vs. 0.994 (*//
      1.033) vs. 0.994 (*// 1.038); Agility test: 1.010 (*//1.050) vs. 1.014 (*//1.050)
      vs. 1.002 (*//1.053). All tests, except heart rate recovery from the Multi-stage
      fitness test, were able to distinguish between different ability and age groups
      of players (p<0.05). Thus, the field-test battery demonstrated logical and
      construct validity, and was shown to be a reliable and objective tool for
      assessing elite, young soccer players.

PMID- 23143703
TI  - Physiological demands of a simulated BMX competition.
AB  - The aim of this study was to investigate the physiological demands of Supercross
      BMX in elite athletes. Firstly athletes underwent an incremental cycling test to
      determine maximal oxygen uptake (VO2max) and power at ventilatory thresholds. In
      a second phase, athletes performed alone a simulated competition, consisting of 6
      cycling races separated by 30 min of passive recovery on an actual BMX track.
      Oxygen uptake, blood lactate, anion gap and base excess (BE) were measured.
      Results indicated that a simulated BMX performed by elite athletes induces a high
      solicitation of both aerobic (mean peak VO2 (VO2peak): 94.3+/-1.2% VO2max) and
      anaerobic glycolysis (mean blood lactate: 14.5+/-4. 5 mmol x L(-1) during every
      race. Furthermore, the repetition of the 6 cycling races separated by 30 min of
      recovery led to a significant impairment of the acid-base balance from the third
      to the sixth race (mean decrease in BE: -18.8+/-7.5%, p<0.05). A significant
      relationship was found between the decrease in BE and VO2peak (r = - 0.73,
      p<0.05), indicating that VO2peak could explain for 54% of the variation in BMX
      performance. These results suggest that both oxygen-dependent and -independent
      fuel substrate pathways are important determinants of BMX performance.

PMID- 23143704
TI  - Decrements in stiffness are restored within 10 min.
AB  - The purpose of this study was to clarify the temporal course of stiffness in the
      muscle-tendon unit after stretching. In 11 male participants, displacement of the
      myotendinous junction on the gastrocnemius medialis muscle was measured
      ultrasonographically during the passive-dorsiflexion test, with the ankle was
      passively dorsiflexed at 1  degrees /s to the end of the range of motion. Passive
      torque, representing resistance to stretch, was also measured using an isokinetic
      dynamometer. On 4 different days, passive-dorsiflexion tests were performed
      before and immediately, 5, 10 or 15 min after stretching, which comprised
      dorsiflexion to end range of motion and holding that position for 1 min, 5 times.
      As a result, end range of motion and passive torque at end range of motion were
      significantly increased after stretching (P<0.05) as compared with each previous
      value. Although stiffness of the muscle-tendon unit was significantly decreased
      immediately and 5 min after stretching (P<0.05), this change recovered within 10
      min. These results suggest that static stretching for 5 min results in
      significantly increased range of motion over 30 min, but significant decreases in
      stiffness of the muscle-tendon unit returned to baseline levels within 5-10 min.

PMID- 23143705
TI  - Seasonal changes in physical performance and heart rate variability in high level
      futsal players.
AB  - The aim of this study was to determine the changes in physical performance and
      resting heart rate variability (HRV) in professional futsal players during the
      pre-season and in-season training periods. 11 athletes took part in the study
      (age=24.3+/-2.9 years; height=176.3+/-5.2 cm; weight=76.1+/-6.3 kg), and
      performed a repeated-sprint ability (RSA) test [6*40 m (20+20 m with a 180
      degrees  change of direction) sprints separated by 20 s of passive recovery] and
      Yo-Yo intermittent recovery test level 1 (Yo-Yo IR1) at 3 different moments
      (M1=beginning of pre-season; M2=end of pre-season; M3=mid in-season). The HRV
      indices were assessed at the same moments. After the short pre-season (3-week),
      mean RSA time (RSAmean) (M1=7.43+/-0.2 s; M2=7.24+/-0.2 s; P=0.003), decrement in
      RSA performance (RSAdecrement) (M1=6.7+/-0.3%; M2=5.0+/-0.9%; P=0.001), and Yo-Yo
      IR1 distance (M1=1.244+/-298 m; M2=1.491+/-396 m; P=0.002) were significantly
      improved (P<0.05). During the in-season (i. e., M3), performance in Yo-Yo IR1 and
      RSAmean were maintained. In contrast, RSAbest (M2=6.89+/-0.2 to M3=6.69+/-0.3;
      P=0.001) was improved and RSAdecrement (M2=5.0+/-0.9% to M3=6.6+/-0.9%; P=0.001)
      was impaired. At M2, there was an increase in HRV vagal-related indices compared
      with M1 that was maintained at M3. In conclusion, after a short pre-season,
      futsal players improved their RSA and Yo-Yo IR1 performance with concomitant
      improvements in HRV. These indices were maintained during the in-season period
      while RSAbest was improved and RSAdecrement impaired. Frequent monitoring of
      these performances and HRV indices may assist with identification of individual
      training adaptations and/or early signs of maladaption.

PMID- 23143706
TI  - Self-identification as a moderator of the relationship between gambling-related
      perceived norms and gambling behavior.
AB  - This research was designed to evaluate social influences and perceived social
      norms on gambling behavior among undergraduate students. Furthermore, this
      research was designed to replicate and extend previous research demonstrating
      that young adults overestimate the prevalence of gambling among peers, and that
      the magnitude of overestimation is positively associated with own use (Larimer
      and Neighbors, Psychol Addict Behav 17:235-243, 2003). We expected that; (1)
      gambling college students would identify more strongly with other gambling
      students compared to other students in general; (2) identification with other
      gambling students would predict gambling behaviors over and above perceived
      prevalence of gambling; and (3) identification with other gambling students would
      moderate the association between perceived social norms and gambling behavior.
      Participants included 1,486 undergraduate students who completed measures
      assessing gambling quantity and frequency, gambling-related perceived descriptive
      norms, and identification with groups. Results revealed that perceived norms for
      gambling were associated with gambling and revealed that students identified more
      strongly with other students than either gamblers or student gamblers. However,
      gambling behavior was more strongly associated with identification with gambling
      students than students in general. There was consistent support for the
      perspective that social identity moderates the association between perceived
      norms for gambling and gambling behavior. This research builds on previous
      examinations of social influences related to gambling and suggests that it may be
      important to consider the overall prevalence of a given behavior before
      considering norms-based intervention approaches. Interventions utilizing social
      norms for gambling may be advised to consider references other than just the
      typical student. 

PMID- 23143707
TI  - Matrigel plug assay: evaluation of the angiogenic response by reverse
      transcription-quantitative PCR.
AB  - The subcutaneous Matrigel plug assay in mice is a method of choice for the in
      vivo evaluation of pro- and anti-angiogenic molecules. However, quantification of
      the angiogenic response in the plug remains a problematic task. Here we report a
      simple, rapid, unbiased and reverse transcription-quantitative PCR (RT-qPCR)
      method to investigate the angiogenic process occurring in the Matrigel plug in
      response to fibroblast growth factor-2 (FGF2). To this purpose, a fixed amount of
      human cells were added to harvested plugs at the end of the in vivo
      experimentation as an external cell tracer. Then, mRNA levels of the pan
      endothelial cell markers murine CD31 and vascular endothelial-cadherin were
      measured by species-specific RT-qPCR analysis of the total RNA and data were
      normalized for human GAPDH or beta-actin mRNA levels. RT-qPCR was used also to
      measure the levels of expression in the plug of various angiogenesis/inflammation
      related genes. The procedure allows the simultaneous, quantitative evaluation of
      the newly-formed endothelium and of non-endothelial/inflammatory components of
      the cellular infiltrate in the Matrigel implant, as well as the expression of
      genes involved in the modulation of the angiogenesis process. Also, the method
      consents the quantitative assessment of the effect of local or systemic
      administration of anti-angiogenic compounds on the neovascular response triggered
      by FGF2.

PMID- 23143708
TI  - Coupling effect between cobalt oxides and carbon for oxygen reduction reaction.
AB  - Same selectivity hides different pathways: The same apparent 4-electron process
      for the oxygen-reduction-reaction hides different pathways over carbon-supported
      cobalt oxide catalysts depending on the potential. At low overpotentials, the ORR
      intermediate HO(2) (-)  preferably disproportionates to oxygen, whereas at high
      overpotentials the disproportionation and reduction reaction occur in parallel.

PMID- 23143709
TI  - Synthesis and application of water-soluble NHC transition-metal complexes.
AB  - We provide an overview on the state-of-the-art in transition-metal complexes
      formed with water-soluble NHC ligands. Paths to introducing water solubility by
      ligand design are elucidated and some general properties of water-soluble NHC
      complexes are highlighted. The enhanced hydrophilicity of water-soluble catalysts
      offers advantages in applications. While studies based on C-C coupling reactions
      still dominate the field, recent reports show water-soluble NHC complexes can be
      applied in metathesis and hydrogenation reactions and turn out to be among the
      best performing catalysts known. Nevertheless, wide areas of this young field
      remain to be investigated, offering great potential for future research.

PMID- 23143710
TI  - A prospective randomized double-blind study to assess the latency and efficacy of
      twin-mix and 2% lignocaine with 1:200,000 epinephrine in surgical removal of
      impacted mandibular third molars: a pilot study.
AB  - INTRODUCTION: A prospective randomized double-blind study was conducted to assess
      the latency and duration of pterygomandibular nerve block with a mixture of 1.8
      ml 2% lignocaine with 1:200,000 epinephrine and 1 ml of 4 mg dexamethasone and
      its impact on postoperative sequelae of surgical extraction of impacted
      mandibular third molars. MATERIAL AND METHODS: The study was conducted as a
      prospective randomized double-blind clinical trial on 20 patients with bilateral
      impaction of mandibular third molars. A total of 40 interventions were included
      for the study, 20 with 2% lignocaine with 1:200,000 epinephrine (study group C,
      control) and 20 with the twin-mix (study group T, twin-mix), with a gap of 1
      month between two interventions in a single patient. After injection of the
      anesthetic solution, the time to anesthetic effect, duration of anesthesia, and
      the need to re-anesthetize the surgical site were recorded. A 10-point visual
      analog scale (VAS) was used to assess the overall pain intensity while injecting
      the study drug, during surgery, and in the postoperative period. pH of the test
      anesthetic solutions was also determined using a pH meter. RESULTS: Twin-mix was
      found to be more basic than 2% lignocaine with 1:200,000 epinephrine. Mean VAS
      value for the pain/sting on local anesthetic injection/block was less in study
      group T. Time of onset of the local anesthetic was significantly less for the
      study group T, 51 +/- 17.5 s when compared with patients in study group C (P less
      than 0.0001). The duration of soft tissue anesthesia was longer for all the
      patients in the study group T. On comparative evaluation between study group C
      and study group T, patients in the control group had more sever swelling and
      reduction in mouth opening in the postoperative period. DISCUSSION: The addition
      of dexamethasone to lignocaine and its administration as an intra-space injection
      significantly shortens the latency and prolongs the duration of the soft tissue
      anesthesia, with improved quality of life in the postoperative period after
      surgical extraction of mandibular third molars.

PMID- 23143711
TI  - Basic imaging properties of an indirect flat-panel detector system employing
      irradiation side sampling (ISS) technology for chest radiography: comparison with
      a computed radiographic system.
AB  - The image quality and potential usefulness for patient skin-dose reduction of a
      newly developed flat-panel detector (FPD) system employing irradiation side
      sampling (ISS) were investigated and compared to a conventional computed
      radiography (CR) system. We used the X-ray beam quality of RQA 9 as noted in the
      standard evaluation method by the International Electrotechnical Commission 62220
      1 to evaluate the image quality of the detector for chest radiography. The
      presampled modulation transfer function (MTF) of the ISS-FPD system was slightly
      higher than that of the CR system in the horizontal direction at more than 2.2
      cycles/mm. However, the presampled MTF of the ISS-FPD system was slightly lower
      than that of the CR system in the vertical direction. The Wiener spectrum of the
      ISS-FPD system showed a 50-65 % lesser noise level than that of the CR system
      under the same exposure condition. The detective quantum efficiency of the ISS
      FPD system was at least twice as great as that of the CR system. We conclude that
      the ISS-FPD system has the potential to reduce the patient skin dose compared to
      a conventional CR system for chest radiography.

PMID- 23143712
TI  - A simple method for accurate liver volume estimation by use of curve-fitting: a
      pilot study.
AB  - In this paper, we describe the effectiveness of our curve-fitting method by
      comparing liver volumes estimated by our new technique to volumes obtained with
      the standard manual contour-tracing method. Hepatic parenchymal-phase images of
      13 patients were obtained with multi-detector CT scanners after intravenous bolus
      administration of 120-150 mL of contrast material (300 mgI/mL). The liver
      contours of all sections were traced manually by an abdominal radiologist, and
      the liver volume was computed by summing of the volumes inside the contours. The
      section number between the first and last slice was then divided into 100 equal
      parts, and each volume was re-sampled by use of linear interpolation. We
      generated 13 model profile curves by averaging 12 cases, leaving out one case,
      and we estimated the profile curve for each patient by fitting the volume values
      at 4 points using a scale and translation transform. Finally, we determined the
      liver volume by integrating the sampling points of the profile curve. We used
      Bland-Altman analysis to evaluate the agreement between the volumes estimated
      with our curve-fitting method and the volumes measured by the manual contour
      tracing method. The correlation between the volume measured by manual tracing and
      that estimated with our curve-fitting method was relatively high (r = 0.98; slope
      0.97; p < 0.001). The mean difference between the manual tracing and our method
      was -22.9 cm(3) (SD of the difference, 46.2 cm(3)). Our volume-estimating
      technique that requires the tracing of only 4 images exhibited a relatively high
      linear correlation with the manual tracing technique.

PMID- 23143713
TI  - First test on three stitching methods with digital detectors used in radiography.
AB  - In medical radiography, a large area of the human body sometimes needs to be
      investigated by means of X-ray examinations, for example, the lower spine. With
      computed radiography (CR) cassettes, due to their large surface area, it is
      possible to make this type of investigation with a single exposure and use of a
      single cassette. With flat-panel digital detectors (DR detectors), due to their
      smaller size and their large cost, it is not possible to make the investigation
      with a single exposure, but multiple exposures are required according to the
      extent of the surface to be irradiated, with merging of two or more radiographic
      images. This operation is called "stitching" because several images are stitched
      together. We have tested three different modes of performing stitching
      examinations: linear, rotational and wide. Our purpose was to highlight the
      differences and issues, taking into account the quality of the images and the
      simplicity of use, with the goal of choosing the best technique. We evaluated the
      methods by three different parameters: the image quality, the ease of use (taking
      into account the time for performing an examination), and the simplicity of
      development. Each method has good qualities, but also its own problems: choosing
      the best technique is not easy, because each has advantages and disadvantages.
      Nowadays, rotational stitching is the most used because the quality of the images
      is very good and we are confident that the images have no parallax errors.
      However, this is not an easy system to develop because there are two different
      mechanical movements to be managed. For this reason, we are improving linear
      stitching, which is easier, but has a worse image quality. Wide stitching is the
      system closer to the CR system and has very good image quality, but the
      difficulty of developing a collimator that allows one to perform the technique
      presents a big hurdle. We conclude that, even though rotational stitching is
      complex and expensive, it is the best technique among those investigated.

PMID- 23143714
TI  - Antineuronal antibodies and infectious pathogens in severe acute pediatric
      encephalitis.
AB  - The pathogenesis of acute encephalitis is divided into either direct infection or
      by immune-mediated inflammation, but the cause is still unknown. This
      retrospective study aimed to screen antineuronal antibodies in children with
      severe acute encephalitis. Thirty-four children (22 boys and 12 girls) underwent
      assessments such as antineuronal antibodies survey for autoimmune encephalitis
      and polymerase chain reaction/viral culture and antibody assays for all commonly
      recognized causes of infectious encephalitis. Sixteen (47.1%) were positive for
      autoantibodies, including antiglutamic acid decarboxylase antibodies in 16 and
      voltage-gated potassium channel complex antibodies in 1. Sixteen patients (47.1%)
      had presumed infectious etiologies, including 6 with influenza, 6 with Mycoplasma
      pneumoniae, 3 with enterovirus, and 1 with herpes simplex virus. In this study,
      influenza and Mycoplasma pneumoniae infection are the main presumed causes of
      severe acute encephalitis in children, although an immune-mediated mechanism may
      also play a role. 

PMID- 23143715
TI  - Pelizaeus-Merzbacher-Like Disease in a Family With Variable Phenotype and a Novel
      Splicing GJC2 Mutation.
AB  - Pelizaeus-Merzbacher-like disease is an autosomal recessive disorder
      characterized by neonatal nystagmus, ataxia, progressive spasticity, and
      development delay and is rarely caused by GJC2 mutations. We report 7 patients
      from a large consanguineous family who had variable severity of Pelizaeus
      Merzbacher-like disease. The 3 youngest of branch A were bedridden by their first
      year because of permanent scissoring of their legs and had severe frontal lobe
      epilepsy. The single patient from branch B was the least affected, being able to
      walk until 12 years of age and had no epilepsy. Brain magnetic resonance imaging
      (MRI) showed hypomyelination. The patients had a novel canonical splicing GJC2 c.
      20+1G>C mutation with a predicted loss of the coding connexin 47 protein. The
      exceptionally large number of patients in this unique family enabled to describe
      the intrafamilial variability of Pelizaeus-Merzbacher-like disease. The predicted
      functional loss of connexin 47 might be associated with a severe form of
      Pelizaeus-Merzbacher-like disease.

PMID- 23143716
TI  - Current practices of the child neurologist in managing sports concussion.
AB  - Given the 2010 position statement issued by the American Academy of Neurology
      that neurologists be consulted on return-to-play decisions following a
      concussion, we surveyed members of the Child Neurology Society to asses clinical
      practice management of concussion among child neurologists. Among the 239
      respondents, the majority continued to rely on the American Academy of
      Neurology's 1997 Practice Parameter to guide their decision-making process.
      Although the 2008 consensus statement from the Third International Conference on
      Concussion in Sport (Zurich Guidelines) is currently considered the most up-to
      date guideline, few respondents relied exclusively on this guideline. More
      respondents who completed continuing medical education on concussion reported
      making clinical decisions based on the Zurich guidelines. The finding that child
      neurologists who completed continuing medical education had a greater familiarity
      with the more recently proposed consensus-based concussion guidelines supports
      the development of additional education in sports concussion at all levels of
      child neurology training. 

PMID- 23143717
TI  - Effects of miglustat on stabilization of neurological disorder in niemann-pick
      disease type C: Iranian pediatric case series.
AB  - Niemann-Pick disease type C is a rare neurodegenerative disorder with autosomal
      recessive inheritance that can be broadly categorized into different forms
      dependent on age at disease onset: pre-/perinatal, early infantile, late
      infantile, juvenile, and adolescent/adult. This study was conducted to define the
      age at onset, clinical manifestations, neuroimaging findings and response to
      treatment in 21 patients diagnosed with Niemann-Pick disease type C and managed
      in the neurology departments of hospitals in Tehran, Iran. The effects of
      miglustat on patient ambulation, fine and gross motor function, swallowing,
      hearing, speech, seizures, psychomotor development, and ocular movements were
      evaluated for up to 26 months of treatment. Ambulation, fine and gross motor
      movements, swallowing, speech, and supranuclear gaze palsy were generally
      stabilized during therapy, and psychomotor delay appeared to be improved in early
      and late-infantile onset patients. However, miglustat had no effect on
      organomegaly or other systemic manifestations of the disease. Miglustat was well
      tolerated. 

PMID- 23143718
TI  - Efficacy of lacosamide as adjunctive therapy in children with refractory
      epilepsy.
AB  - Lacosamide is a US Food and Drug Administration (FDA)-approved antiepileptic drug
      for patients 17 years or older with partial epilepsy. There are sparse data on
      children. The objective of our study was to evaluate its efficacy/safety in
      children with refractory epilepsy. Forty children (mean age 14.3 years) were
      treated with lacosamide at our institution (adjunctive therapy in 36, monotherapy
      in 4). Fifteen patients had symptomatic focal epilepsy, 2 had cryptogenic focal
      epilepsy, 20 had symptomatic generalized epilepsy, and 3 had cryptogenic
      generalized epilepsy. Two had juvenile myoclonic epilepsy and 5 had Lennox
      Gastaut syndrome. Forty-two percent had at least >50% reduction in seizure
      frequency, and 6 became seizure free. Average dose was 7 mg/kg/d and average
      follow-up was 9.2 months. Responders had a 76.5% mean decrease in seizures.
      Fifteen children experienced an adverse reaction and 7 discontinued lacosamide
      (4: Ineffective, I: insurance denial, 1: tremor, 1: behavior). Lacosamide is
      effective and well-tolerated in children with refractory epilepsy. 

PMID- 23143719
TI  - A comparative study of primary and secondary stereotypies.
AB  - This study compares primary stereotypies (repetitive, self-stimulating, and
      seemingly nonsensical movements that can occur within typically developing
      children) and secondary stereotypies (those occurring within autistic or mentally
      retarded children). Utilizing a retrospective chart review from 1995 to 2010, the
      current study compares primary and secondary stereotypies by the application of a
      classification system that organizes the movement by its type (motor only, phonic
      only, mixed) and complexity. In addition, it investigates other parameters
      associated with the movements such as duration, frequency, age, functional
      impairment, and progression. The sample group consisted of 28 primary and 28
      secondary cases. Primary stereotypies were predominantly motor, simple, of
      shorter duration, and of less frequency, whereas secondary stereotypies had more
      vocalization, complexity, longer durations, and higher frequencies. Moreover,
      functional impairment due to stereotypies was noted in 3 primary and 7 secondary
      cases, and worsening of stereotypies was noted in 70% of primary versus 44% of
      secondary cases. 

PMID- 23143720
TI  - Prevention of Traumatic Brain Injury in Youth and Adolescents.
AB  - The goal of this project was to promote bicycle helmet use via an inpatient
      educational program. We hypothesized that this program would increase bicycle
      helmet use. One hundred twenty inpatients with history of regular (>1 time per
      week) bicycle riding (mean age 10.0 +/- 3.6 years; 67 males, 53 females; 57
      whites, 59 blacks, 4 other) were randomized to treatment (n = 58) or control (n =
      62) groups. All participants received a bicycle helmet. At 1 month, 50 (92.6%) of
      the intervention group and 48 (82.8%) of the control group wore a helmet every
      bike ride (P < .07). At 3 months, 50 (96.2%) of the intervention group and 44
      (80%) of the controls wore a helmet with every bike ride (P < .03). The study
      proved feasible, requiring trained personnel to deliver the intervention.
      Providing a helmet without the intervention was effective in 80% to 83% of cases
      with respect to parental report of helmet wearing compliance.

PMID- 23143721
TI  - Predictors of Epilepsy in Children With Cerebrovascular Disease.
AB  - Post-stroke seizures and epilepsy in children are a common but understudied
      complication. In this retrospective cohort study, the medical records of 65
      children aged 0 to 18 years were analyzed to assess the risk of post-stroke
      seizures, detect the prevalence of post-stroke epilepsy, and ascertain which risk
      factors are associated with this condition in children. Forty-two patients
      (64.6%) had epileptic seizures following stroke (35 early, 7 late-onset), with
      most (78.5%) occurring in the first 24 hours. Nineteen children (29.2%) developed
      post-stroke epilepsy, which was significantly more common among patients with
      late-onset seizures (P = .034). There was a significant association between
      cortical involvement and development of epilepsy (P = .01). After Poisson
      regression, the relative risk of epilepsy was calculated as 2.4 in children with
      late-onset post-stroke seizures (95% confidence interval, 1.4-3.9; P = .001) and
      3.7 in children with cortical involvement (95% confidence interval, 1.4-9.7; P =
      .009).

PMID- 23143722
TI  - Headaches in children with craniopharyngioma.
AB  - Craniopharyngioma frequently involves intracranial pain-sensitive structures. We
      retrospectively studied prevalence, associated risk factors, and outcome of
      headaches in children with craniopharyngioma. Fisher exact test and multivariate
      analysis were used to study association of study variables. Of the 51
      craniopharyngioma patients treated at our institution from January 1994 to
      December 2005, 40 (78%) reported headaches (35 [68%] before tumor diagnosis).
      Migraine headaches were diagnosed in 32 (63%) and tension-type headaches in 11
      patients (22%). The median follow-up period was 2.7 years. At the last follow-up,
      38 (75%) were headache free. Presence of hydrocephalus, distortion of circle of
      Willis, and large tumor volume were associated with headache, and the last 2
      variables were also associated with more severe and frequent headaches. Radiation
      treatment and insertion of Ommaya reservoir were associated with reduced headache
      frequency. In conclusion, headaches are common in patients with craniopharyngioma
      and are likely related to tumor size and volume. In most patients, headaches
      improve with successful tumor treatment. 

PMID- 23143723
TI  - Cognitive trajectories in 4 patients with pediatric-onset multiple sclerosis:
      serial evaluation over a decade.
AB  - Cognitive dysfunction is common in pediatric-onset multiple sclerosis, but long
      term data on cognitive maturation in these patients are sparse. We report the
      clinical features and cognitive trajectories in 4 pediatric-onset multiple
      sclerosis patients who were 10 years or younger at first attack and were followed
      between 1998 and 2010. Relapses in all 4 patients were frequent early in the
      disease and became infrequent or absent over time. Declines on neuropsychological
      testing were most pronounced on measures of processing speed, specifically
      visuomotor speed, and executive control requiring mental sequencing and set
      shifting, whereas global intellectual ability and phonemic fluency remained
      stable or improved over time. These case studies demonstrate a negative impact of
      multiple sclerosis on cognitive development in the long term and suggest that
      continued observation into adulthood is required to appreciate the vocational
      consequences of pediatric-onset multiple sclerosis. 

PMID- 23143724
TI  - Acute disseminated encephalomyelitis: the time until diagnosis and its subsequent
      course in children.
AB  - Acute disseminated encephalomyelitis has an acute onset followed by improvement
      over several weeks. However, some cases require more time for a definitive
      diagnosis after protracted psychiatric or nonspecific symptoms. The authors
      investigated the time from onset to definitive diagnosis, subsequent course of
      treatment, and outcomes in 7 children with acute disseminated encephalomyelitis
      treated at the authors' hospital. The mean duration of illness before definitive
      diagnosis was 20.7 days (range: 2-50 days). Steroid pulse therapy was performed
      in all cases, and rapid improvements were observed; the mean duration from
      treatment initiation to hospital discharge was 8.6 days (range: 4-14 days). None
      of the cases showed neurological sequelae. Although this study investigated a
      small number of patients, its results suggest that time to diagnosis is often
      longer in children than in adults, and even in cases of delayed treatment,
      response to steroid pulse therapy is good and outcomes may not necessarily be
      affected. 

PMID- 23143725
TI  - Atypical face processing in children with tuberous sclerosis complex.
AB  - There is a high incidence of autism in tuberous sclerosis complex. Given the
      evidence of impaired face processing in autism, the authors sought to investigate
      electrophysiological markers of face processing in children with tuberous
      sclerosis complex. The authors studied 19 children with tuberous sclerosis
      complex under age 4, and 20 age-matched controls, using a familiar-unfamiliar
      faces paradigm. Of the children, 6 with tuberous sclerosis complex (32%) had
      autism. Children with tuberous sclerosis complex showed a longer N290 latency
      than controls (276 ms vs 259 ms, P = .05) and also failed to show the expected
      hemispheric differences in face processing. The longest N290 latency was seen in
      (1) children with autism and tuberous sclerosis complex and (2) children with
      temporal lobe tubers. This study is the first to quantify atypical face
      processing in children with tuberous sclerosis complex. This functional
      impairment may provide insight into a mechanism underlying a pathway to autism in
      tuberous sclerosis complex. 

PMID- 23143726
TI  - Hyperekplexia: a Chinese adolescent with 2 novel mutations of the GLRA1 gene.
AB  - Hyperekplexia is a rare neurologic disorder, characterized by excessive startle
      response to unexpected stimuli. There are 3 cardinal features: generalized
      stiffness immediately after birth that normalizes during the first year of life;
      excessive startle reflex to unexpected (particularly auditory) stimuli; and a
      short period of generalized stiffness following the startle response while
      patient cannot elicit voluntary movements. Awareness of this condition will avoid
      misdiagnosis of disorders like epilepsy. Clonazepam is an effective medical
      treatment. We report a patient whose frequent falls triggered by sudden noise or
      tactile stimuli was initially misdiagnosed as epilepsy. The clinical diagnosis
      was subsequently revised to hyperekplexia and confirmed by mutation analysis of
      the GLRA1 gene, which showed c.497G>C (p.Cys166Ser) and c.526delG
      (p.Asp176Metfs*16). Both of them are novel mutations. His response to clonazepam
      is dramatic and has been able to engage in sports and social activities. 

PMID- 23143727
TI  - Late occurrence of isolated obsessive-compulsive behavior in a boy with Wilson's
      Disease on treatment.

PMID- 23143728
TI  - Epilepsy surgery for early infantile epileptic encephalopathy (ohtahara
      syndrome).
AB  - Early infantile epileptic encephalopathy or Ohtahara syndrome is the earliest
      form of the age-dependent epileptic encephalopathies. Its manifestations include
      tonic spasms, focal motor seizures, suppression burst pattern, pharmaco
      resistance, and dismal prognosis. The purpose of this study was to evaluate the
      effectiveness of epilepsy surgery in selected infants. We identified 11 patients,
      9 from the literature and 2 from our institution that fulfilled diagnostic
      criteria of Ohtahara syndrome and had undergone epilepsy surgery in infancy.
      Seven of the 11 infants have remained seizure free (Engel class IA) and four are
      reportedly having rare to infrequent seizures (Engel class IIB). All patients
      experienced "catch up" development. In contrast to Ohtahara's15 pharmacotherapy
      managed patients, who had a mortality rate of approximately fifty percent, and
      those that survived continued to have seizures and were severely impaired, the
      outcome of selected surgically managed patients is much more favorable. 

PMID- 23143729
TI  - Early spinal cord and brainstem involvement in infantile Leigh syndrome possibly
      caused by a novel variant.
AB  - Leigh syndrome, due to a dysfunction of mitochondrial energy metabolism, is a
      genetically heterogeneous and progressive neurologic disorder that usually occurs
      in infancy and childhood. Its clinical presentation and neuroimaging findings can
      be variable, especially early in the course of the disease. This report presents
      a patient with infantile Leigh syndrome who had atypical radiologic findings on
      serial neuroimaging studies with early and severe involvement of the cervical
      spinal cord and brainstem and injury to the thalami and basal ganglia occurring
      only late in the clinical course. Postmortem microscopic examination supported
      this timing of injury within the central nervous system. In addition,
      mitochondrial deoxyribonucleic acid sequencing showed a novel homoplasmic variant
      that could be responsible for this unique lethal form of Leigh syndrome. 

PMID- 23143730
TI  - Health care needs of children with Tourette syndrome.
AB  - To document the impact of Tourette syndrome on the health care needs of children
      and access to health care among youth with Tourette syndrome, parent-reported
      data from the 2007-2008 National Survey of Children's Health were analyzed.
      Children with Tourette syndrome had more co-occurring mental disorders than
      children with asthma or children without Tourette syndrome or asthma and had
      health care needs that were equal to or greater than children with asthma (no
      Tourette syndrome) or children with neither asthma nor Tourette syndrome. Health
      care needs were greatest among children with Tourette syndrome and co-occurring
      mental disorders, and these children were least likely to receive effective care
      coordination. Addressing co-occurring conditions may improve the health and well
      being of children with Tourette syndrome. Strategies such as integration of
      behavioral health and primary care may be needed to improve care coordination. 

PMID- 23143731
TI  - Photoluminescent DNA binding and cytotoxic activity of a platinum(II) complex
      bearing a tetradentate beta-diketiminate ligand.
AB  - A platinum(II) complex of a monoanionic, tetradentate beta-diketiminate (BDI)
      ligand with pendant quinoline arms, BDI(QQ)H, is reported. The complex,
      [Pt(BDI(QQ))]Cl, is emissive in DMSO, but non-emissive in aqueous buffer. Upon
      binding DNA in buffer, however, a 150-fold turn-on in emission intensity occurs.
      Dynamic light scattering and (1)H NMR spectroscopy indicate that [Pt(BDI(QQ))]Cl
      forms non-emissive aggregates in aqueous solution; DNA-binding disperses the
      aggregates leading to the large emission turn-on response. The cytotoxic activity
      of the complex, measured in two cancer cell lines, is comparable to or better
      than that of the established anticancer drug cisplatin.

PMID- 23143732
TI  - Pharmacologic management of chronic reno-cardiac syndrome.
AB  - Chronic kidney disease (CKD) significantly increases cardiovascular morbidity and
      mortality. CKD remains an under-represented population in cardiovascular clinical
      trials, and cardiovascular disease is an under-treated entity in CKD. Traditional
      cardiovascular risk factors in conjunction with uremia-related complications
      often progress to myocardial dysfunction. Such uremic cardiomyopathy leads to
      over-activation of neurohormonal pathways with detrimental effects. Management of
      the reno-cardiac syndrome (RCS) requires the targeting of these multiple facets.
      In this article we discuss the relevant pathophysiology of RCS, and present the
      clinical data related to its management.

PMID- 23143733
TI  - Positive urine cytology and carcinoma in situ prior to second transurethral
      resection of the bladder correlate with positive second resection histology and
      the need for subsequent cystectomy.
AB  - OBJECTIVE: A second transurethral resection of the bladder (TURB) is recommended
      for high-grade bladder cancer (BC) yet yields negative results in over half of
      the cases. Aim of this study was to identify prognostic indicators of a positive
      second TURB or the need for a subsequent cystectomy. MATERIALS AND METHODS: The
      study cohort consisted of 101 patients with high-risk BC (T1G2-3, TaG3, Carcinoma
      in situ) who underwent second TURB after complete first resection. Age, gender,
      stage, grade, carcinoma in situ (Cis), tumour number, size, localization, surgeon
      experience and bladder wash cytology before the second TURB were considered as
      potential prognostic factors of positive histology at second TURB or the need for
      subsequent cystectomy. RESULTS: The mean follow-up period was 23.8 months. The
      study cohort was comprised of 82 males and 17 females. Cytology on bladder wash
      urine was performed in 85/101 patients and in 39 was negative; 55.5 % of second
      TURB specimens were negative. The rate of upstaging to >=T2 was 4.9 %. Cis (OR
      8.4; 95 % CI 1.3-54.2; p = 0.03) and positive cytology (OR 6.8; 95 % CI 2.3-19.9;
      p = <0.01) were independent prognostic factors of a residual tumour in the second
      TURB. Cytology also correlated with clinical need for cystectomy in the follow-up
      (HR 6.5; 95 % CI 1.3-30.5; p = 0.02). CONCLUSIONS: CIS and positive cytology
      prior to second TURB increased the risk of a positive second TURB specimen. A
      positive cytology also increases the risk of the subsequent need for cystectomy.

PMID- 23143734
TI  - PDE5 inhibition against acute renal ischemia reperfusion injury in rats: does
      vardenafil offer protection?
AB  - PURPOSE: To evaluate the effect of vardenafil on renal function after renal
      ischemia-reperfusion (IR) injury (IRI) in a rat model. MATERIALS AND METHODS:
      Seventy-one Wistar rats were divided into 7 groups including (1) a vehicle
      treated group, (2) a vehicle pretreated-IR group, (3-6) vardenafil pretreated-IR
      groups in doses of 0.02, 0.2, 2 and 20 MUg/kg, respectively, (7) a group of IR
      followed by treatment with 2 MUg/kg of vardenafil. Vardenafil or vehicle solution
      was administered one hour before unilateral nephrectomy and the induction of 45
      min of ischemia on the contralateral kidney by clamping of renal pedicle. Four
      hours of reperfusion were allowed after renal ischemia. Studied parameters were
      serum creatinine, fractional excretion of sodium (FENa), and histological
      evaluation of renal specimens. In addition, renal tissue cGMP levels, ERK1/2
      phosphorylation as well as renal function by renal scintigraphy were also
      evaluated. RESULTS: Administration of vardenafil before the induction of ischemia
      resulted in a significant reduction in creatinine and FENa levels as well as in
      less histological lesions observed in treated kidneys in comparison with the
      vehicle-treated group. The underlying mechanism of cytoprotection was cGMP
      depended and involved the phosphorylation of ERK proteins. Renal scintigraphy
      confirmed that PDE5 inhibition attenuates renal IRI. CONCLUSIONS: Vardenafil
      attenuates renal IRI. Based on similar results from relevant studies on other PDE
      5 inhibitors in renal and cardiac IRI, it can be assumed that all PDE-5
      inhibitors share a common mechanism of cytoprotection.

PMID- 23143735
TI  - Anthropometric and clinical factors associated with mortality in subjects with
      nonalcoholic fatty liver disease.
AB  - AIM: Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of
      metabolic syndrome and may be associated with increased mortality. Our aim was to
      determine whether anthropometric measures are independently associated with
      mortality in NAFLD. METHODS: The third National Health and Nutrition Examination
      Surveys (1988-1994) data was used. Extensive radiologic, serologic and clinical
      data were available. NAFLD was defined as moderate-to-severe hepatic steatosis on
      the hepatic ultrasound in the absence of any cause of chronic liver disease (e.g.
      hepatitis C virus RNA negative, hepatitis B-surface antigen negative, normal
      transferrin saturation and alcohol consumption <20 gram/day). Anthropometric
      measures [body mass index (kg/m(2)), waist, hip, arm, and thigh circumferences
      (cm), waist-to-hip ratio, percentage of body fat, and sum of skinfolds (mm)],
      laboratory measures and clinico-demographic data were analyzed. Statistical
      analyses were conducted with SUDAAN 10.0. RESULTS: A total of 10,565 adult
      participants were included [2,510 (weighted 21 %) with NAFLD and 8,055 non-NAFLD
      controls]. In multivariate analysis, NAFLD was independently associated with
      being Mexican-American (including Hispanic or other ethnicity), larger waist
      circumference (cm), type-2 diabetes, insulin resistance and hypertension. After
      about 14 years (median) of follow up, liver-specific mortality was independently
      associated with NAFLD and being White. CONCLUSIONS: Components of metabolic
      syndrome, and Mexican-American ethnicity are independently associated with NAFLD.
      Furthermore, NAFLD is an independent predictors of liver-specific mortality in
      men and Whites.

PMID- 23143736
TI  - Grape seed extract reduces the severity of selected disease markers in the
      proximal colon of dextran sulphate sodium-induced colitis in rats.
AB  - BACKGROUND: Grape seed extract (GSE) constitutes a rich source of procyanidins.
      GSE has been demonstrated to exert encouraging anti-inflammatory and anti-ulcer
      properties in experimental settings, although its effects on inflammation of the
      colon remain undefined. AIM: To determine the effects of GSE in a rat model of
      dextran sulphate sodium (DSS) for ulcerative colitis. METHODS: Male Sprague
      Dawley rats were gavaged daily (days 0-10) with GSE (400 mg/kg). Ulcerative
      colitis was induced by substituting DSS (2 % w/v) for drinking water from days 5
      10. A sucrose breath test was performed on day 11 to determine small bowel
      function and intestinal tissues were collected for histological analyses.
      Statistical analysis was by one-way or repeated-measures ANOVA and p < 0.05 was
      considered significant. RESULTS: Compared to DSS-treated controls, GSE
      significantly decreased ileal villus height (14 %; p < 0.01) and mucosal
      thickness (13 %; p < 0.01) towards the values of normal controls. GSE reduced
      qualitative histological severity score (p < 0.05) in the proximal colon,
      although no significant effect was evident in the distal colon. However, GSE
      failed to prevent DSS-induced damage to the crypts of both colonic regions.
      Administration of GSE did not negatively impact metabolic parameters, nor did it
      induce any deleterious gastrointestinal side effects in healthy animals.
      CONCLUSIONS: GSE decreased the severity of selected markers of DSS-induced
      colitis in the distal ileum and proximal colon, suggesting the potential as an
      adjuvant therapy for the treatment of ulcerative colitis. Future studies of GSE
      should investigate alternative delivery methods and treatment regimens, further
      seeking to identify the individual bioactive factors.

PMID- 23143737
TI  - Prone positioning of obese patients for colonoscopy results in shortened cecal
      intubation times: a randomized trial.
AB  - BACKGROUND: Obesity is a risk factor for colorectal cancer, and colonoscopy can
      be technically challenging in obese patients. It has been proposed (with little
      supporting data) that prone positioning of obese patients might facilitate a
      difficult colonoscopy. AIM: The aim of this study was to determine if starting
      colonoscopy in the prone position for obese patients decreases cecal intubation
      times. METHODS: This was a prospective, randomized study conducted at the North
      Texas VA Medical Center. Patients with a body mass index of >=30 kg/m(2)
      undergoing elective colonoscopy were randomized 1:1 to either initial prone
      positioning or standard, left-lateral positioning. The outcome measurements were
      cecal intubation time, frequency of repositioning, sedative medications used,
      reports of pain, complications, and procedure tolerability. RESULTS: Fifty
      patients were randomized to have colonoscopy starting in the standard, left
      lateral decubitus position, and 51 to the prone position. The average cecal
      intubation time for the standard group was 550 vs. 424 s in the prone group (p =
      0.03). Patient repositioning was used in 28 % of patients in the standard group
      versus 8 % in the prone group (p = 0.009). There was no difference in subjective
      reports of pain between groups (p = 0.95) or in average pain scores (p = 0.79).
      Follow-up interviews were conducted in 93 % of patients, all of whom said that
      they would be willing to have repeat colonoscopy in the same position.
      CONCLUSIONS: Performance of colonoscopy in the prone position for obese patients
      results in significantly shorter cecal intubation times and decreased need for
      patient repositioning. Prone positioning is well accepted and does not
      significantly increase procedure-related discomfort.

PMID- 23143738
TI  - Prospects of raising Sahiwal cow calves for veal production under tropical
      environment.
AB  - The objective of present study was to evaluate the growth potential of Sahiwal
      calves for veal production on whole milk or whole milk and milk replacer combined
      in a ratio of 50:50 (MMR). For this purpose, 48 Sahiwal calves (both male and
      female) were assigned to four dietary treatments having 12 animals/treatment.
      Calves in the treatments A and B were offered whole milk at 15 or 20% of their
      body weight (BW), respectively, up to day 84 adjusted on weekly basis. The calves
      in treatments C and D received the same amount of milk as in treatments A and B
      until day 21, respectively, after which 50% of the milk offered was replaced with
      a blend of chickpea (Cicer arietinum) flour and vegetable (corn) oil mixed in
      water (MR) until day 84. The constituted MR had 3.1, 2.8, and 14.3%, CP, EE, and
      DM, respectively. The growth and intake data were analyzed using repeated
      measures analysis, with MIXED Procedures of SAS in a 2 * 2 factorial design. The
      two factors were feeding level and feeding source. Calves offered whole milk grew
      faster (P<0.05) and had greater weaning weights (P<0.05) than those offered MMR
      (606.4 +/- 18.1 vs 331.3 +/- 18.1 g/day and 70.4 +/- 1.5 vs 47.8 +/- 1.5 kg,
      respectively). Greatest daily BW gain (656 +/- 26 g/day) and weaning weight (74.6
      +/- 2.1 kg) were observed in calves given treatment B while the lowest production
      cost/kg of BW gain (~US$3.6 +/- 0.2) was observed in calves given treatment A.
      The daily BW gain of calves fed milk ad libitum was 716 +/- 40 and 836 +/- 40
      g/day, during 5-8 and 9-12 weeks, respectively. The number of days calves
      exhibited scours was higher in calves offered MMR than those offered whole milk.
      Replacement of 50% milk with a blend of chickpea flour and vegetable oil, as an
      alternative to milk replacer, did not support growth equivalent to whole milk and
      was not effective in reducing feeding cost during the weaning period. Sahiwal
      calves may have promise for being raised for veal production under tropical
      environments.

PMID- 23143739
TI  - Effect of farrowing duration, parity number and the type of anti-inflammatory
      drug on postparturient disorders in sows: a clinical study.
AB  - The aim of the present study was to investigate the effects of farrowing
      duration, parity number, and type of anti-inflammatory drug used postpartum on
      the incidence of postparturient disorders in sows. The duration of farrowing and
      postparturient disorders were examined in 64 sows at Days 0, 1, 2, and 3 after
      farrowing. The sows were classified according to parity number (1, 2-4, and 5-7),
      duration of farrowing (<2, 2-2.9, 3-3.9, and 4-8 h), and the type of anti
      inflammatory drugs (flunixin meglumine and dipyrone). The farrowing duration was
      178.0 +/- 73.5 min (2.96 h). The percentage of sows with fever increased from 40
      to 100 % when the farrowing duration increased from <2 to 4-8 h. On Day 1 of the
      postpartum, 93.7 % of primiparous sows had fever, while 52.6 and 47.6 % of sows
      parity 2-4 and 5-7 had a fever (P<0.05). The presence of vaginal discharge on Day
      1 of the postpartum was higher in sows of parity 5-7 than sows of parity 2-4
      (85.7 and 52.6 %, P=0.029). The use of flunixin meglumine after parturition in
      sows reduced the percentage of sows with a fever from 61.3 to 22.6 % within 2
      days (P=0.002), while, the percentage of sows with a fever was not decreased in
      sows treated with dipyrone. It can be concluded that the incidence of
      postparturient disorders in sows was affected by sow parity, farrowing duration
      and the type of anti-inflammatory drug used. Sows with a farrowing duration of >=
      4 h were at a high risk of having fever at Day 1 after parturition.

PMID- 23143740
TI  - O-GlcNAc modification prevents peptide-dependent acceleration of alpha-synuclein
      aggregation.
AB  - Sweet relief: the Parkinson's disease- associated protein alpha-synuclein is post
      translationally modified by N-acetylglucosamine (O-GlcNAc), but the biochemical
      consequences are unknown. Here we show that an O-GlcNAc-modified peptide does not
      participate in alpha-synuclein aggregation, thus suggesting that O-GlcNAc might
      directly inhibit aggregation in cells.

PMID- 23143741
TI  - A case of complete lateral gaze paralysis and facial diplegia:  the 16 syndrome.
AB  - We describe a patient with complete, bilateral horizontal gaze palsies and facial
      diplegia caused by a midline tegmental pontine hemorrhage. The term "16 syndrome"
      (7 + 7 + 1/2 + 1/2 + 1/2 + 1/2 = 16) describes this combination of clinical
      findings.

PMID- 23143743
TI  - Quantitative evaluation of light scattering intensities of the crystalline lens
      for radiation related minimal change in interventional radiologists: a cross
      sectional pilot study.
AB  - To evaluate low-dose X-ray radiation effects on the eye by measuring the amount
      of light scattering in specific regions of the lens, we compared exposed subjects
      (interventional radiologists) with unexposed subjects (employees of medical
      service companies), as a pilot study. According to numerous exclusionary rules,
      subjects with confounding variables contributing to cataract formation were
      excluded. Left eye examinations were performed on 68 exposed subjects and 171
      unexposed subjects. The eye examinations consisted of an initial screening
      examination, followed by Scheimpflug imaging of the lens using an anterior eye
      segment analysis system. The subjects were assessed for the quantity of light
      scattering intensities found in each of the six layers of the lens. Multiple
      stepwise regression analyses were performed with the stepwise regression for six
      variables: age, radiation exposure, smoking, drinking, wearing glasses and
      workplace. In addition, an age-matched comparison between exposed and unexposed
      subjects was performed. Minimal increased light scattering intensity in the
      posterior subcapsular region showed statistical significance. Our results
      indicate that occupational radiation exposure in interventional radiologists may
      affect the posterior subcapsular region of the lens. Since by its very nature
      this retrospective study had many limitations, further well-designed studies
      concerning minimal radiation-related lens changes should be carried out in a low
      dose exposure group.

PMID- 23143744
TI  - Single immunization with a suboptimal antigen dose encapsulated into
      polyanhydride microparticles promotes high titer and avid antibody responses.
AB  - Microparticle adjuvants based on biodegradable polyanhydrides were used to
      provide controlled delivery of a model antigen, ovalbumin (Ova), to mice. Ova was
      encapsulated into two different polyanhydride microparticle formulations to
      evaluate the influence of polymer chemistry on the nature and magnitude of the
      humoral immune response after administration of a suboptimal dose. Subcutaneous
      administration of a single dose of polyanhydride microparticles containing 25 MUg
      of Ova elicited humoral immune responses that were comparable in magnitude to
      that induced by soluble doses of 400-1600 MUg Ova. In contrast, the avidity of
      the Ova-specific antibodies was greater in mice administered the microparticle
      formulations in comparison to the higher soluble doses. Finally, the
      microparticle delivery system primed an anamnestic immune response as evidenced
      by the significant increases in Ova-specific antibody when mice were administered
      an antigenic challenge of 25 MUg of Ova at 12 weeks post-vaccination. Together,
      these results indicate that encapsulation of antigens into polyanhydride
      microparticles facilitates isotype switching, establishes immunologic memory, and
      the humoral response was characterized by a higher quality antibody response.

PMID- 23143745
TI  - Soluble conjugated microporous polymers.

PMID- 23143746
TI  - Intratumoral peptide injection enhances tumor cell antigenicity recognized by
      cytotoxic T lymphocytes: a potential option for improvement in antigen-specific
      cancer immunotherapy.
AB  - Antigen-specific cancer immunotherapy is a promising strategy for improving
      cancer treatment. Recently, many tumor-associated antigens and their epitopes
      recognized by cytotoxic T lymphocytes (CTLs) have been identified. However, the
      density of endogenously presented antigen-derived peptides on tumor cells is
      generally sparse, resulting in the inability of antigen-specific CTLs to work
      effectively. We hypothesize that increasing the density of an antigen-derived
      peptide would enhance antigen-specific cancer immunotherapy. Here, we
      demonstrated that intratumoral peptide injection leads to additional peptide
      loading onto major histocompatibility complex class I molecules of tumor cells,
      enhancing tumor cell recognition by antigen-specific CTLs. In in vitro studies,
      human leukocyte antigen (HLA)-A*02:01-restricted glypican-3144-152 (FVGEFFTDV)
      and cytomegalovirus495-503 (NLVPMVATV) peptide-specific CTLs showed strong
      activity against all peptide-pulsed cell lines, regardless of whether the tumor
      cells expressed the antigen. In in vivo studies using immunodeficient mice,
      glypican-3144-152 and cytomegalovirus495-503 peptides injected into a solid mass
      were loaded onto HLA class I molecules of tumor cells. In a peptide vaccine model
      and an adoptive cell transfer model using C57BL/6 mice, intratumoral injection of
      ovalbumin257-264 peptide (SIINFEKL) was effective for tumor growth inhibition and
      survival against ovalbumin-negative tumors without adverse reactions. Moreover,
      we demonstrated an antigen-spreading effect that occurred after intratumoral
      peptide injection. Intratumoral peptide injection enhances tumor cell
      antigenicity and may be a useful option for improvement in antigen-specific
      cancer immunotherapy against solid tumors.

PMID- 23143747
TI  - TRAIL suppresses tumor growth in mice by inducing tumor-infiltrating CD4(+)CD25
      (+) Treg apoptosis.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a promising and
      novel anticancer cytokine, specifically kills numerous tumor cells by apoptosis.
      However, some malignancies are resistant to TRAIL treatment in clinical trials,
      thus limiting its therapeutic potential. In the present study, the TRAIL
      resistant murine hepatocellular carcinoma cell line Hepa1-6 was used to elucidate
      the physiological significance of TRAIL resistance, especially with respect to
      the immune regulatory function of TRAIL. Hepa1-6 cells were resistant to TRAIL
      induced apoptosis in vitro; however, intratumoral injection of recombinant
      soluble TRAIL inhibited tumor growth and prolonged survival time in tumor-bearing
      mice. Local TRAIL treatment decreased the number of intratumoral
      CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) but did not affect
      CD4(+)CD25(+)Foxp3(+) Tregs in the draining lymph nodes and spleen. Further
      investigation showed that TRAIL induced apoptosis of tumor-activated
      CD4(+)CD25(+)Foxp3(+) Tregs, but not of CD4(+)CD25(-) T cells. Moreover, mouse
      TRAIL receptor DR5 expression was detected on the surface of the tumor
      infiltrating CD4(+)CD25(+)Foxp3(+) Tregs, but not on naive CD4(+)CD25(+)Foxp3(+)
      Tregs. Interestingly, intratumoral injection of TRAIL not only decreased the
      number of CD4(+)CD25(+)Foxp3(+) Tregs but also increased the number of tumor
      specific CD8(+) CTL and augmented their cytotoxicity to the tumor cells. These
      data provide the novel evidence for an immune regulatory function of TRAIL and
      may shed light on the clinical application of TRAIL.

PMID- 23143748
TI  - The influence of perceived health on labour participation among long term
      unemployed.
AB  - BACKGROUNDS: Few studies have addressed the specific contribution of health in
      relation to socio-demographic and motivational aspects to re-entering paid
      employment. The purpose of this study among beneficiaries of unemployment
      benefits is to evaluate the detrimental effects of poor health and a lack of
      motivation on the likelihood of getting a job and to develop a decision support
      model that predicts remaining unemployment after 12 months. METHODS: A
      longitudinal cohort study was conducted among people on unemployment benefit (UB)
      or social insurance benefit (SIB). The time-window of the study was 18 months.
      Written questionnaires were filled out 3 months post-benefit assessment, 6, 12
      and 18 months. Multivariate logistic regression analysis was used to identify the
      barriers of re-entering paid employment. Subsequently, a predictive model was
      constructed to estimate the probability for every combination of determinants for
      a person to remain unemployed in the next 12 months. RESULTS: Older age (>=55
      years), a poor perceived health, and a lack of willingness to accept a job were
      the most prominent predictive factors for remaining unemployed after 12 months in
      both UB and SIB groups. Lower education in the UB group and being married or
      living together and poor self-reliance in the SIB group were additional risk
      factors for long-term unemployment. CONCLUSION: Vocational rehabilitation of
      people on long-term social benefit should address perceived health, socio
      demographic, and motivational aspects as key factors that determine prolonged
      unemployment. A predictive flow chart can be used to detect most vulnerable
      persons at risk for remaining long-term unemployment.

PMID- 23143749
TI  - Falls among adult patients hospitalized in the United States:  prevalence and
      trends.
AB  - OBJECTIVES: The purpose of this study was to provide normative data on fall
      prevalence in U.S. hospitals by unit type and to determine the 27-month secular
      trend in falls before the implementation of the Centers for Medicare and Medicaid
      Service (CMS) rule, which does not reimburse hospitals for care related to injury
      resulting from hospital falls. METHODS: We used data from the National Database
      of Nursing Quality Indicators (NDNQI) collected between July 1, 2006, and
      September 30, 2008, to estimate prevalence and secular trends of falls occurring
      in adult medical, medical-surgical, and surgical nursing units. More than 88
      million patient days (pd) of observation were contributed from 6100 medical,
      surgical, and medical-surgical nursing units in 1263 hospitals across the United
      States. RESULTS: A total of 315,817 falls occurred (rate = 3.56 falls/1000 pd)
      during the study period, of which, 82,332 (26.1%) resulted in an injury (rate =
      0.93/1000 pd). Both total fall and injurious fall rates were highest in medical
      units (fall rate = 4.03/1000 pd; injurious fall rate = 1.08/1000 pd) and lowest
      in surgery units (fall rate = 2.76/1000 pd; injurious fall rate = 0.67/1000 pd).
      Falls (0.4% decrease per quarter, P < 0.0001) and injurious falls (1% decrease
      per quarter, P < 0.0001) both decreased over the 27-month study. CONCLUSIONS: In
      this large sample, fall and injurious fall prevalence varied by nursing unit type
      in U.S. hospitals. Over the 27-month study, there was a small, but statistically
      significant, decrease in falls (P < 0.0001) and injurious falls (P < 0.0001).

PMID- 23143750
TI  - Forced sexual initiation, sexual intimate partner violence and HIV risk in women:
      a global review of the literature.
AB  - Coerced or forced sexual initiation and sexual intimate partner violence (sexual
      IPV) contribute significantly to a woman's risk for HIV infection. This review
      systematically examines global research (n = 21 studies) published since 2000 on
      the role of coerced/forced sexual initiation and sexual IPV on HIV risk in women.
      In predominantly low- and middle-income countries, coerced/forced sexual
      initiation was associated with HIV/STIs, multiple and high-risk sex partners, and
      no condom use. Most studies using behaviorally specific terms for sexual IPV
      found strong associations between sexual IPV and HIV risk behaviors. In contrast,
      studies using less specific definitions often failed to find these significant
      associations. To develop more comprehensive HIV prevention programs, future
      efforts should integrate behaviorally specific terms into assessing prevalence of
      sexual IPV and its association with HIV risk, consider cultural differences, and
      identify causal pathways between coerced or forced sexual initiation, HIV risk
      behaviors and HIV/STI infection.

PMID- 23143751
TI  - Personal HIV knowledge, appointment adherence and HIV outcomes.
AB  - HIV knowledge may impact patient access, understanding, and utilization of HIV
      medical information. This study explored the relationship between personal HIV
      knowledge, appointment adherence and treatment outcomes. HIV-infected individuals
      (n = 210) were assessed on factors related to HIV knowledge and appointment
      adherence. Adherence data and laboratory values were extracted from medical
      records. HIV knowledge was measured by participants' knowledge of their CD4 count
      and viral load (VL) and adherence was defined as attendance at >75 % of
      appointments. Two-thirds of participants were adherent, but only one-third knew
      their CD4 count and VL. Controlling for time since last appointment, HIV
      knowledge more than doubled the odds of appointment adherence. In combination
      with relationship with provider, knowledge predicted increased CD4 count and
      increased odds of an undetectable VL by almost five times. Personal HIV knowledge
      may be a valuable indicator of engagement in care and may also facilitate
      improved treatment outcomes.

PMID- 23143752
TI  - Mycobacterium tuberculous peritonitis in CAPD patients: a report of 11 patients
      and review of literature.
AB  - BACKGROUND: The aims of the present report were to document our experience of the
      prevalence of tuberculous peritonitis in continuous ambulatory peritoneal
      dialysis (CAPD) patients, mode of presentation, diagnosis and outcome and to
      discuss the current published data about catheter removal. METHODS: A
      retrospective study of CAPD patients with tuberculous peritonitis was done. A
      minimum of three specimens of peritoneal fluid were examined for acid-fast
      bacilli smears. The BACTEC 9000 Blood Culture Series of instruments were used for
      the culture of Mycobacterium tuberculosis. After 2005, patients were treated with
      anti-tuberculous treatment, and catheter retention was started in our patients.
      RESULTS: There were eleven patients (2.6 %) with tuberculous peritonitis among
      414 CAPD patients. M. tuberculosis accounted for 4.47 % of all peritonitis
      episodes. The incidence of tuberculous peritonitis was 1/794 months. There were
      eight males and three females. The mean age was 49 years. Intestinal obstruction
      was reported in two patients, and two patients were treated for antecedent
      peritonitis. One of them had a simultaneous fungal peritonitis. One patient each
      developed a peritoneo-cutaneous fistula and ultrafiltration failure. Three were
      successfully treated without the removal of catheter. CONCLUSION: Based on the
      analysis of all published reports of tuberculous peritonitis, there was no
      significant difference in patient survival between patients in whom CAPD catheter
      was removed or retained. Tuberculous peritonitis should be considered in patients
      with neutrophilic 'sterile' peritonitis with no response to antibacterial
      medications, predominance of lymphocytic peritonitis and in bacterial peritonitis
      not responding to antibiotics. After an early diagnosis, with close monitoring,
      an effort to retain the catheter after 5 days of anti-tuberculous therapy may be
      attempted.

PMID- 23143753
TI  - Effects of high-efficiency postdilution online hemodiafiltration and high-flux
      hemodialysis on serum phosphorus and cardiac structure and function in patients
      with end-stage renal disease.
AB  - BACKGROUND/AIM: Cardiovascular disease is the leading cause of mortality in
      patients with chronic kidney disease and has a strong association with
      hyperphosphatemia. Dialysis is the major treatment tool for attaining serum
      phosphorus control. Phosphorus removal can be increased with hemodiafiltration.
      We compared the effect of hemodiafiltration and hemodialysis on serum phosphorus
      and phosphorus removal and changes in cardiovascular variables in a short-term
      follow-up. METHODS: Adult patients with end-stage renal disease were randomized
      to receive hemodialysis or hemodiafiltration for 3 months. Clinical and
      biochemical variables were recorded monthly. Cardiac resonance was done at
      randomization and at the end of follow-up. RESULTS: A total of 24 patients were
      studied (10 in hemodialysis and 14 in hemodiafiltration) with a mean age of 34.7
      +/- 11.4 years. The two groups did not differ as for age and blood pressure
      control at baseline. Phosphorus removal was higher (1,099 +/- 239 in
      hemodiafiltration vs. 864 +/- 366 mmol/session in hemodialysis, p < 0.05) and
      serum phosphorus was lower in the hemodiafiltration group at the end of follow-up
      (3.4 +/- 0.8 in hemodiafiltration vs. 4.5 +/- 1.6 mg/dl in hemodialysis, p <
      0.05). We found a significant increase in ejection fraction only in the
      hemodiafiltration group. There was a trend to smaller increase in myocardial mass
      and a decrease in left ventricular end-diastolic volume only in the
      hemodiafiltration group. The changes in cardiac variables were significantly
      associated with changes in serum phosphorus levels. CONCLUSION: Hemodiafiltration
      was associated with better control of serum phosphorus and improvement in left
      ventricular ejection fraction, compared with hemodialysis.

PMID- 23143755
TI  - Pollution-induced oxidative stress and biochemical parameter alterations in the
      blood of white stork nestlings Ciconia ciconia from regions with different
      degrees of contamination in Poland.
AB  - This paper aimed to illustrate the most reliable biomarkers to detect pollution
      related oxidative stress in white stork nestlings in polluted (from copper
      manufacture), suburban and Odra meadows (as a control area) areas . Lipid
      peroxidation (thiobarbituric acid reactive substances content, TBARS) and
      oxidative modified protein levels (stable 2,4-dinitrophenyl hydrazine derivates
      of the carbonyl groups) were used as indicators of the oxidative stress, as well
      as other selected biochemical parameters, which are used as diagnostic tools in
      avian medicine (alanine and aspartate aminotransferases, lactate dehydrogenase
      activities, lactate and pyruvate concentrations). It was found that the blood of
      chicks from the polluted area was more susceptible to oxidative stress due to
      lipid peroxidation and protein oxidation, manifested as protein carbonyls, the
      elevation of alanine and aspartate aminotransferases activities, and lactate and
      pyruvate concentrations than those of chicks from suburban and Odra meadows
      areas. Direct connections between lactate and pyruvate concentrations and lipid
      peroxidation (TBARS level), as well as between derivates of carbonyl oxidation
      levels in the blood of chicks from the polluted area were detected. Lactate
      dehydrogenase activity was slightly inhibited in the blood of chicks from the
      polluted environment, perhaps because of increased lactate concentration in the
      blood of chicks from polluted areas. It can be suggested that alanine and
      aspartate aminotransferases, lactate dehydrogenase activities, lactate and
      pyruvate concentrations can be used as indicators of oxidative stress. The
      activities of these enzymes were perhaps not directly related to environmental
      pollution, but more likely to some secondary pollution-related changes in the
      nestlings' conditions.

PMID- 23143756
TI  - Associations of polymorphisms in the genes of FGFR2, FGF1, and RBFOX2 with breast
      cancer risk by estrogen/progesterone receptor status.
AB  - Genetic polymorphisms of fibroblast growth factor receptor 2 (FGFR2) have been
      demonstrated to be associated with breast cancer risk, presumably through
      elevation of FGFR2 expression. Fibroblast growth factor 1 (FGF1) and RNA binding
      protein fox-1 homolog 2 (RBFOX2), which are functionally related to FGFR2, may
      also associate with breast cancer risk. We investigated the associations between
      breast cancer risk and the polymorphisms of FGFR2 rs2981582, FGF1 rs250108, and
      RBFOX2 rs2051579 among 839 incident breast cancer cases and 863 age-matched
      controls in the Guangzhou Breast Cancer Study. Stratified odds ratios (ORs) and
      95% confidence intervals (CIs) were calculated by estrogen receptor
      (ER)/progesterone receptor (PR) status using multivariate logistic regression.
      FGFR2 rs2981582 was confirmed to be significantly associated with the risk of ER
      positive but not ER-negative breast cancer. In contrast, FGF1 rs250108 was
      significantly associated with the risk of ER-negative breast cancer (OR (95% CI)
      = 1.68 (1.20-2.35) for CT + TT vs. CC genotype) but not ER-positive breast
      cancer. CA + AA genotypes at RBFOX2 rs2051579 were associated with a reduced risk
      of ER-negative (0.71 (0.52-0.97)) but not ER-positive breast cancer compared to
      the CC genotype. Similar results were observed when differentiating breast cancer
      cases by PR status. Neither of the pairs between the three SNPs had a significant
      interaction on breast cancer risk. Our findings show a suggestively stronger
      association between FGFR2 rs2981582 and ER-positive breast cancer risk and
      suggest a greater association of FGF1 rs250108 and RBFOX2 rs2051579 with ER
      negative compared to ER-positive breast cancer.

PMID- 23143757
TI  - Marine cyanobacterial fatty acid amides acting on cannabinoid receptors.
AB  - Striking cAMP: certain fatty acid amides from marine cyanobacteria can mimic the
      endocannabinoids. Serinolamide B, a new analogue identified from a Guamanian
      sample, and malyngamide B, a representative member of a large class of
      cyanobacterial metabolites, can decrease forskolin-induced cAMP accumulation
      through the cannabinoid receptors.

PMID- 23143758
TI  - Persistence of retinal function after intravitreal melphalan injection for
      retinoblastoma.
AB  - BACKGROUND: The risk/benefit profile of intravitreal melphalan injection for
      treatment of active vitreous seeds in retinoblastoma remains uncertain. We report
      clinical and electroretinography results after 6 months of one patient who has
      shown a favorable initial clinical response to intravitreal melphalan injections
      for treatment of refractory vitreous seeds. METHODS: Clinical case report.
      PATIENT: The patient presented at age 17 months with bilateral retinoblastoma
      [OD: International Classification (ICRB) group E, Reese-Ellsworth (R-E) class Vb;
      OS: ICRB D, R-E Vb] with no known prior family history. The right eye was
      enucleated primarily. The patient received systemic chemotherapy and extensive
      local treatment to the left eye. Ten months later, she presented with recurrent
      disease, including fine, diffuse vitreous seeds. Tumor control was established
      with intra-arterial chemotherapy and local treatment. Subsequent recurrence was
      treated with further intra-arterial chemotherapy, local treatment, and plaque
      radiotherapy with iodine-125. Persistent free-floating spherical vitreous seeds
      were treated with 4 cycles of intravitreal melphalan injection via the pars
      plana, with doses of 30, 30, 30, and 20 MUg. RESULTS: After 6 months of follow
      up, the left eye remained free of active tumor. Visual acuity was 20/40. Photopic
      ERGs amplitudes were unchanged compared with those recorded prior to the
      intravitreal injection treatments. CONCLUSIONS: Intravitreal melphalan injection
      for refractory spherical vitreous seeds of retinoblastoma with favorable tumor
      response is compatible with good central visual acuity and preservation of
      retinal function as indicated by photopic ERG recordings.

PMID- 23143759
TI  - A comparison of the performance of three visual evoked potential-based methods to
      estimate visual acuity.
AB  - PURPOSE: To compare visual acuities estimated by three methods of visual evoked
      potential (VEP) recordings to those obtained by two subjective measures [ETDRS
      and FrACT (Freiburg acuity test)]. METHODS: Ten healthy subjects, aged between 26
      and 67 years (mean 43.5), were examined. Best-corrected acuity determined by the
      ETDRS was between 0.03 and -0.3 logMAR (mean -0.06). Sweep VEPs (sweepVEP),
      pattern appearance VEPs (pappVEP) and steady-state VEPs (ssVEP) were recorded
      with two electrode placements (10-20 and Laplace) with best optical correction
      and with artificially degraded vision using five Bangerter occlusion foils,
      reducing acuity to about 0.1, 0.22, 0.52, 0.7 and 1.0 logMAR (0.8, 0.6, 0.3, 0.2
      and 0.1 decimal scale). Two runs were performed. RESULTS: ETDRS and FrACT
      acuities showed good agreement, even though ETDRS seemed to underestimate acuity
      compared with FrACT at higher acuities. Laplace derivation did not improve any of
      the VEP-estimated acuities over the 10-20. SweepVEP tended to overestimate lower
      FrACT acuities, but showed good repeatability. PappVEP placed FrACT acuities into
      correct or neighboring categories in 87 % of cases. Average ssVEP acuity showed
      little difference to those of FrACT but variance was larger. ROC analysis for
      typical clinical application showed good performance for all three methods.
      CONCLUSIONS: The two subjective measurements of acuities are well correlated.
      Under the conditions of our experiment, sweepVEP results were less variable and
      had a better repeatability than ssVEP acuities, whose analysis, in contrast to
      sweepVEP, can be automated. PappVEP estimates, however, offer a viable
      alternative, that is, quicker but of lower performance regarding the detection of
      low acuity thresholds. All methods had a good performance regarding minimum
      acuity detection if an average of two runs is used.

PMID- 23143760
TI  - [Treatment of children and adolecents with cancer after the application of the
      guide lines for good clinical practice in 2004 and the evaluation of new
      measurements].

PMID- 23143761
TI  - Current concepts for diagnosis and treatment of retinoblastoma in Germany: aiming
      for safe tumor control and vision preservation.
AB  - Retinoblastoma affects approximately 40 children in Germany per year. Most
      children are diagnosed early with localized intraocular disease, and the overall
      survival rate exceeds 95%. However, the prognosis of metastasized retinoblastoma
      remains poor. In 40% of the patients, retinoblastoma occurs bilaterally and,
      especially for these children, the salvage of the eye and visual function is of
      major importance. The variety of conservative treatment options for localized
      retinoblastoma includes laser coagulation, thermotherapy, cryotherapy,
      brachytherapy and chemotherapy. While systemic chemotherapy has nearly completely
      replaced external beam radiotherapy in the primary treatment of intraocular
      retinoblastoma, intra-arterial, intravitreal and periocular application of
      chemotherapy was also shown to be effective in treating intraocular
      retinoblastoma in case series. Genetic testing is an integral part of the routine
      diagnostics of all patients. Available tumor material should be analyzed to
      detect mutational mosaicism, that affects >10% of children with unilateral
      retinoblastoma. Genetic testing also identifies children with heritable (50% of
      patients) retinoblastoma. These children have a genetic predisposition for second
      malignancies. For this reason, late effects are an increasing concern and the
      care of patients with retinoblastoma requires a multidisciplinary approach to
      tailor therapy and long-term follow-up. Multicenter clinical trials are being
      developed to evaluate evidence-based treatment concepts for localized and
      metastasized retinoblastoma to improve survival rates and quality of life of
      children with retinoblastoma.

PMID- 23143762
TI  - Ewing sarcoma of the hand or foot.
AB  - PURPOSE: Ewing Sarcoma (ES) of the hand or foot is a rare clinical condition. Due
      to the critical site, it is of major importance to choose an optimal procedure
      for local control in terms of outcome and function. Local therapeutic options for
      these patients range from: surgery (OP), surgery followed by radiotherapy (OP &
      RT), or radiotherapy (RT) alone. PATIENTS AND METHODS: Data from 80 patients with
      ES of the hand or foot were analyzed. All patients received chemotherapy
      according to the protocols of the Cooperative Ewing Sarcoma Study Group (CESS)
      from 1991 to 2009 (EICESS-92 and EURO-E.W.I.N.G.99). Local therapy consisted of:
      OP in 39%, OP & RT in 44%, and RT in 12%. In 5% of the patients no local therapy
      (noL) was performed. Primary endpoint of our study was the event-free-survival
      (EFS). RESULTS: The 3-year overall EFS was 62% (95%CI 0.50-0.72). Patients with
      localized disease had a significantly better outcome with an EFS of 77% (95%CI
      0.63-0.86), compared to patients with primary disseminated disease with an EFS of
      30% (95%CI 0.14-0.49; p<0.001). In comparing local treatment modalities, no
      significant difference was observed. The 3-year EFS for OP was 61% (95% CI 0.40
      0.76), for OP & RT 66% (95%CI 0.47-0.79) and for RT only 70% (95%CI 0.32-0.89)
      (p=0.253). Patients who did not receive local treatment had an unfavourable
      prognosis (3-year EFS=0.25; 95%CI 0.01-0.67; p=0.024). A multivariate analysis
      which included local treatment modality and known prognosticators, showed that
      primary dissemination was the only significant prognostic factor.Ewing sarcoma of
      the hand or foot is associated with a favourable outcome. CONCLUSION: Our data
      analysed a limited group of patients and thus did not provide a clear indication
      for a preferred local treatment modality.

PMID- 23143763
TI  - Molecular genetic analysis of bilateral ovarian germ cell tumors.
AB  - BACKGROUND: Ovarian germ cell tumors (oGCTs) are rare and highly heterogeneous
      with regard to their clinical and histologic appearance. The risk of tumor
      development is higher in children with aberrant sexual differentiation.
      Development of gonadoblastomas is seen in young women with 46,XY gonadal
      dysgenesis. At least 50 % of gonadoblastomas may develop into malignant oGCTs,
      mostly dysgerminomas. In this study, we evaluated bilateral oGCTs in clinically
      inapparent patients for sex chromosomal aberrations. PATIENTS AND METHODS: We
      analyzed tumor samples of 15 patients with synchronous bilateral oGCTs enrolled
      onto the consecutive MAKEI trials for non-testicular GCTs. Paraffin embedded
      samples from the Kiel German Childhood Tumor Registry were evaluated for the
      presence of Y-chromosomal sequences. Molecular genetic techniques included
      comparative genomic hybridization, polymerase chain reaction, and fluorescence in
      situ hybridization. RESULTS: Among 15 patients with bilateral oGCTs, Y
      chromosomal DNA sequences were detected in 6 tumors. Both mature teratomas were
      negative for Y-chromosomal DNA. Thus, 5 of 12 malignant oGCTs and 1 immature
      teratoma (with elevated AFP) showed Y-chromosomal material. A 45(X,0) karyotype
      could not be demonstrated. CONCLUSIONS: These investigations provide additional
      insight into the development of oGCTs: mature teratomas, which develop from
      postmeiotic germ cells, are not associated with gonadal dysgenesis. Bilateral
      immature teratomas, dysgerminomas and mixed malignant oGCTs may frequently show Y
      chromosomal DNA, indicating underlying but clinically inapparent gonadal
      dysgenesis. Thus, the presence of aberrant Y-chromosomal sequences appears to be
      involved in tumor development in about half of these patients.

PMID- 23143764
TI  - Systemic treatment of adrenocortical carcinoma in children: data from the German
      GPOH-MET 97 trial.
AB  - BACKGROUND: Adrenocortical cancer (ACC) in childhood is a rare disease with poor
      prognosis. Complete surgical resection, systemic chemotherapy, and mitotane
      therapy are important curative treatment options for patients with advanced-stage
      tumors. Since 1997, pediatric ACC patients in Germany have been treated according
      to the non-randomized, single arm study GPOH-MET-97. PATIENTS AND METHODS: Data
      regarding disease course, treatment, and survival rates of 60 patients (age 0.24
      17.8 years) with ACC treated according to the GPOH-MET-97 protocol were collected
      and analyzed to determine outcome, with a focus on examining the effectiveness of
      mitotane therapy. RESULTS: Among all patients, event-free survival and overall
      survival were found to be 43.3% and 64.8%, respectively. Chemotherapy with VCR,
      IFO, ADR, CARBO, and VP16 had been provided to 34 patients (56.6%) in different
      settings (neoadjuvant, adjuvant, and salvage) and mitotane therapy to 32 patients
      (53.3%). Duration of mitotane treatment longer than 6 months and mitotane levels
      greater than 14 mg/l were found to be associated with significantly better
      survival. Local relapse was found to be associated with a worse prognosis
      compared to distant metastasis only. CONCLUSIONS: Systemic chemotherapy and
      mitotane therapy are important therapeutic options in the treatment of advanced
      pediatric ACC patients. Neoadjuvant therapy should be considered for patients
      with primarily incomplete resectable or inoperable tumors, and tumor spillage is
      an indication for adjuvant chemo- and mitotane therapy. All pediatric ACC
      patients should be treated in pediatric oncological centers according to a
      consistent protocol in a highly interdisciplinary setting.

PMID- 23143765
TI  - Fatal EBV infection and variable clinical manifestations in an XLP-1 pedigree -
      rapid diagnosis of primary immunodeficiencies may save lives.
AB  - Two related boys who died from fulminant infectious mononucleosis were diagnosed
      with X-linked lymphoproliferative disease type 1 (XLP-1). Family screening (n=17)
      identified 6 female mutation carriers and 2 more XLP-1 patients in whom, despite
      recurrent infections, agammaglobulinemia, and Hodgkin's Disease, the genetic
      basis had been unknown; demonstrating that awareness and early genetic testing
      are crucial to reveal underlying primary immunodeficiencies and improve outcome.
      Furthermore, XLP should be included routinely in the differential diagnosis of
      severe hypogammaglobulinemia and/or lymphoma in males.

PMID- 23143766
TI  - Prenatal suspicion of Kaposiform hemangioendo-thelioma in siblings: different
      clinical manifestation and emergency relief.

PMID- 23143767
TI  - [Infantile hepatic hemangiomas: first-line propranolol monotherapy as new
      treatment strategy?].

PMID- 23143768
TI  - [Interdisciplinary AWMF guideline for the treatment of primary antibody
      deficiencies].
AB  - BACKGROUND: Currently, management of antibody deficient patients differs
      significantly among caregivers. Evidence and consensus based (S3) guidelines for
      the treatment of primary antibody deficiencies were developed to improve the
      management of these patients. METHODS: Based on a thorough analysis of current
      evidence (systematic literature search in PubMed; deadline November 2011) 14
      recommendations were finalized during a consensus meeting in Frankfurt in
      November 2011 using structured consensus methods (nominal group technique).
      Experts were nominated by their scientific societies/patient initiatives (Tab.
      1). RESULTS: The guidelines focus on indication, practical issues and monitoring
      of immunoglobulin replacement therapy as well as on different routes of
      administration. Furthermore recommendations regarding supportive measures such as
      antiinfective therapy, vaccinations and physiotherapy are given. Combining
      literature evidence and experience of caregivers within this evidence and
      consensus based guidelines offers the chance to improve the quality of care for
      anti-body deficient patients.

PMID- 23143769
TI  - Rare cancers in children - The EXPeRT Initiative: a report from the European
      Cooperative Study Group on Pediatric Rare Tumors.
AB  - The low incidence and the heterogeneity of very rare tumors (VRTs) demand for
      international cooperation. In 2008, EXPeRT (European Cooperative Study Group for
      Pediatric Rare Tumors) was founded by national groups from Italy, France, United
      Kingdom, Poland and Germany. The first aims of EXPeRT were to agree on a uniform
      definition of VRTs and to develop the currently most relevant scientific
      questions. Current initiatives include international data exchange, retrospective
      and prospective studies of specific entities, and the development of harmonized
      and internationally recognized guidelines. Moreover, EXPeRT established a network
      for expert consultation to assist in clinical decision in VRTs.

PMID- 23143770
TI  - A versatile aqueous reduction of bio-based carboxylic acids using syngas as a
      hydrogen source.
AB  - Syngas as a versatile hydrogen source: Using readily available and economically
      favorable syngas as a convenient hydrogen source, an efficient and sustainable
      aqueous reduction of bio-based carboxylic acids has been achieved over a highly
      robust catalyst system consisting of gold nanoparticles supported on acid
      tolerant single-phase monoclinic zirconia (Au/m-ZrO(2)). A range of bio-based
      multifunctional carboxylic acids have been selectively converted into their
      corresponding lactones or diols in high to excellent yields.

PMID- 23143771
TI  - Assessing willingness to pay for improved sanitation in rural Vietnam.
AB  - OBJECTIVE: The willingness to pay (WTP) for the construction of bathrooms with a
      flush toilet was assessed in households in a rural community in northern Vietnam.
      We also examined the effects of socio-economic factors on the WTP. METHODS: The
      contingent valuation method, an economic survey technique, was used. We used the
      iterative bidding game technique to elicit household WTP that involved a sequence
      of dichotomous choice questions followed by a final open-ended question. A total
      of 370 households that did not have toilets were selected for this study.
      Respondents to the questionnaire were the primary income earners and decision
      makers of their respective household. RESULTS: Of those responding to the
      questionnaire, 62.1 % reported being willing to pay for the construction of
      bathrooms with a flush toilet. The mean and median of maximum WTP amounts were
      Viet Nam Dong (VND) 15.6 million and VND 13.0 million, respectively (minimum VND
      2.0 million; maximum VND 45.0 million). Significant correlates of the WTP rate
      were: (1) gender of the head of household, (2) age of the head of household, (3)
      economic status of household, (4) type of current toilet, (5) satisfaction with
      existing toilet, and (6) knowledge of health effects of poor sanitation. The
      significant determinants of WTP amount were (1) geographic location and (2)
      economic status of household. CONCLUSION: About two-third of the households in
      the study area were willing to pay for an improvement in their current sanitation
      arrangements. Both WTP rate and WP amount were strongly influenced by the
      economic status of the households and health knowledge of the study respondents.

PMID- 23143772
TI  - Protective antibody responses against Clostridium difficile elicited by a DNA
      vaccine expressing the enzymatic domain of toxin B.
AB  - A DNA vaccination approach was used in the current study to screen for the
      immunogenicity of different fragments of toxin A and toxin B from Clostridium
      difficile. With this approach, protein antigens do not need to be produced in
      vitro and the immunogenicity of candidate C. difficile antigens can be identified
      directly in animals. Codon optimized toxin gene fragments were individually
      cloned into the DNA vaccine vector and tested in mice and rabbits for their
      ability to elicit C. difficile toxin-specific antibody responses. Only a subset
      of the C. difficile toxin fragments, including the C-terminal receptor binding
      domain of toxin A and a novel N-terminal enzymatic domain of toxin B, were able
      to elicit protective antibody responses as determined by protection of target
      cells in a cytotoxicity assay or by preventing death of mice in a passive
      antibody protection study. Significantly, antibodies elicited by the novel N
      terminus of the toxin B DNA vaccine were able to increase the level of protection
      when used in combination with anti-toxin A antibodies in a toxin challenge model
      in mice.

PMID- 23143773
TI  - Safety and immunogenicity of an FP9-vectored candidate tuberculosis vaccine
      (FP85A), alone and with candidate vaccine MVA85A in BCG-vaccinated healthy
      adults: a phase I clinical trial.
AB  - The safety and immunogenicity of a new candidate tuberculosis (TB) vaccine, FP85A
      was evaluated alone and in heterologous prime-boost regimes with another
      candidate TB vaccine, MVA85A. This was an open label, non-controlled, non
      randomized Phase I clinical trial. Healthy previously BCG-vaccinated adult
      subjects were enrolled sequentially into three groups and vaccinated with FP85A
      alone, or both FP85A and MVA85A, with a four week interval between vaccinations.
      Passive and active data on adverse events were collected. Immunogenicity was
      evaluated by Enzyme Linked Immunospot (ELISpot), flow cytometry and Enzyme Linked
      Immunosorbent assay (ELISA). Most adverse events were mild and there were no
      vaccine-related serious adverse events. FP85A vaccination did not enhance antigen
      85A-specific cellular immunity. When MVA85A vaccination was preceded by FP85A
      vaccination, cellular immune responses were lower compared with when MVA85A
      vaccination was the first immunisation. MVA85A vaccination, but not FP85A
      vaccination, induced anti-MVA IgG antibodies. Both MVA85A and FP85A vaccinations
      induced anti-FP9 IgG antibodies. In conclusion, FP85A vaccination was well
      tolerated but did not induce antigen-specific cellular immune responses. We
      hypothesize that FP85A induced anti-FP9 IgG antibodies with cross-reactivity for
      MVA85A, which may have mediated inhibition of the immune response to subsequent
      MVA85A. ClinicalTrials.gov identification number: NCT00653770.

PMID- 23143774
TI  - Assessing the burden of HPV-related cancers in Appalachia.
AB  - Appalachia is a geographic region with existing cancer disparities, yet little is
      known about its burden of HPV-related cancers outside of cervical cancer. We
      assessed the burden of HPV-related cancers in three Appalachian states and made
      comparisons to non-Appalachian regions. We examined 1996-2008 cancer registry
      data for Ohio, Kentucky, West Virginia and the Surveillance, Epidemiology and End
      Results (SEER) 9 program. For each gender, we calculated age-adjusted incidence
      rates per 100,000 population for each HPV-related cancer type (cervical, vaginal,
      vulvar, penile, anal and oral cavity and pharyngeal cancers) and all HPV-related
      cancers combined. Incidence rates among females for all HPV-related cancers
      combined were higher in Appalachian Kentucky [24.6 (95% CI: 23.5-25.7)], West
      Virginia [22.8 (95% CI: 22.0-23.6)] and Appalachian Ohio [21.9 (95% CI: 21.0
      22.8)] than SEER 9 [18.8 (95% CI: 18.6-19.0)]. Similar disparities were found
      among females when examining cervical and vulvar cancers separately. Among males,
      Appalachian [21.3 (95% CI: 20.2-22.4)] and non-Appalachian [21.9 (95% CI: 21.2
      22.7)] Kentucky had higher incidence rates for all HPV-related cancers combined
      than SEER 9 [18.3 (95% CI: 18.1-18.6)]. The incidence rate of all HPV-related
      cancers combined was higher among males from Appalachian Ohio compared with those
      from non-Appalachian Ohio [17.6 (95% CI: 16.8-18.5) vs. 16.3 (95% CI: 16.0
      16.6)]. Our study suggests that HPV-related cancer disparities exist in
      Appalachia beyond the known high cervical cancer incidence rates. These results
      have important public health implications by beginning to demonstrate the
      potential impact that widespread HPV vaccination could have in Appalachia.

PMID- 23143775
TI  - Effectiveness of adjuvanted seasonal influenza vaccines (Inflexal V (r) and Fluad
      (r) ) in preventing hospitalization for influenza and pneumonia in the elderly: a
      matched case-control study.
AB  - Annual vaccination is the main mean of preventing influenza in the elderly. In
      order to evaluate the effectiveness of the adjuvanted seasonal influenza vaccines
      available in Italy in preventing hospitalization for influenza and pneumonia, a
      matched case-control study was performed in elderly subjects during the 2010-2011
      season in Genoa (Italy). Cases and controls were matched in a 1:1 ratio according
      to gender, age, socio-economic status and type of influenza vaccine. Vaccine
      effectiveness was calculated as IVE = [(1-OR)x100] and crude odds ratios were
      estimated through conditional logistic regression models. Adjusted odds ratios
      were estimated through multivariable logistic models. In the study area,
      influenza activity was moderate in the 2010-2011 season, with optimal matching
      between circulating viruses and vaccine strains. We recruited 187 case-control
      pairs; 46.5% of cases and 79.1% of controls had been vaccinated. The adjuvanted
      influenza vaccines (Fluad ((r))  considered together with Inflexal V ((r)) ) were
      associated with a significant reduction in the risk of hospitalization, their
      effectiveness being 94.8% (CI 77.1-98.8). Adjusted vaccine effectiveness was
      95.2% (CI 62.8-99.4) and 87.8 (CI 0.0-98.9) for Inflexal V ((r))  and Fluad ((r))
      , respectively. Both adjuvanted vaccines proved effective, although the results
      displayed statistical significance only for Inflexal V ((r))  (p = 0.004), while
      for Fluad ((r))  statistical significance was not reached (p = 0.09). Our study
      is the first to provide information on the effectiveness of Inflexal V ((r))  in
      terms of reducing hospitalizations for influenza or pneumonia in the elderly, and
      demonstrates that this vaccine yields a high degree of protection and that its
      use would generate considerable saving for the National Health Service.

PMID- 23143776
TI  - Porous calcium polyphosphate as load-bearing bone substitutes: in vivo study.
AB  - Porous calcium polyphosphate (CPP) is being investigated for fabrication of novel
      biodegradable bone substitutes. In this study, porous CPP implants formed by
      conventional CPP powder packing and using a two-step sinter/anneal process was
      used to form 20 and 30 vol % porous samples displaying relatively high strength.
      These were implanted in rabbit femoral condyle sites to study their ability for
      secure fixation in prepared sites through bone ingrowth. Porous implants of 20
      and 30 vol % porosity and displaying compressive strengths ~80 and 35 MPa,
      respectively, were used. Bone ingrowth sufficient to allow secure implant
      fixation was observed by 6 weeks (~19% bone ingrowth per available pore space for
      the 30 vol % and 13% for the 20 vol % porous implants). The results of the in
      vivo study suggest the potential usefulness of porous CPP as biodegradable bone
      substitutes/augments in high load-bearing skeletal regions.

PMID- 23143777
TI  - Targeting a regulatory element in human thymidylate synthase mRNA.
AB  - Thymidylate synthase (TS) is a key enzyme in the biosynthesis of thymidine. The
      use of TS inhibitors in cancer chemotherapy suffers from resistance development
      in tumors through upregulation of TS expression. Autoregulatory translation
      control has been implicated with TS overexpression. TS binding at its own mRNA,
      which leads to sequestration of the start codon, is abolished when the enzyme
      forms an inhibitor complex, thereby relieving translation suppression. We have
      used the protein-binding site from the TS mRNA in the context of a bicistronic
      expression system to validate targeting the regulatory motif with stabilizing
      ligands that prevent ribosomal initiation. Stabilization of the RNA by mutations,
      which were studied as surrogates of ligand binding, suppresses translation of the
      TS protein. Compounds that stabilize the TS-binding RNA motif and thereby inhibit
      ribosomal initiation might be used in combination with existing TS enzyme
      targeting drugs to overcome resistance development during chemotherapy.

PMID- 23143778
TI  - A phase I, open-label, single-arm study for QT assessment of eribulin mesylate in
      patients with advanced solid tumors.
AB  - BACKGROUND: Several cancer therapies can prolong cardiac repolarization. This
      study assessed the potential of eribulin to affect cardiac repolarization in
      patients with advanced solid tumors. METHODS: In this Phase I, open-label, single
      arm study, patients received eribulin mesylate (1.4 mg/m(2); Days 1 and 8 of a 21
      day cycle). The primary objective was to assess the effect of eribulin on the
      QTcF pre- and post-infusion; QTcF and QTcNi were compared for ability to remove
      heart-rate dependence of the QT interval. Relationship between concentration of
      eribulin and DeltaQTc was explored using linear mixed-effects analysis. Secondary
      objectives explored pharmacokinetics, safety, and tolerability. RESULTS: Twenty
      six patients were enrolled. QTcNi was more effective than QTcF in correcting for
      heart-rate dependency of the QT interval. On Day 1, mean DeltaQTcNi were ~0 at
      all timepoints. An apparent time-dependent increase in DeltaQTc was observed: on
      Day 8, changes from baseline were larger and more variable, without clear
      relation to plasma levels of eribulin. Day 8 predose DeltaQTcNi was 5 ms, post
      infusion mean values ranged from 2 to 9 ms (largest mean DeltaQTcNi at 6 h). No
      new or unexpected toxicities were reported. CONCLUSION: Eribulin demonstrated an
      acceptable safety profile and a minor prolongation of QTc not expected to be of
      clinical concern in oncology patients.

PMID- 23143779
TI  - Preclinical evaluation of the AKT inhibitor MK-2206 in nasopharyngeal carcinoma
      cell lines.
AB  - Nasopharyngeal carcinoma (NPC) is endemic to Asia and over 40 % of NPC tissues
      harbor PIK3CA amplifications. This study characterized the preclinical activity
      of MK-2206, an oral allosteric inhibitor of AKT in 6 NPC cell lines: C666-1, HK1,
      HONE-1-EBV, HONE-1, CNE-2 and HNE-1. Exposure to increasing concentrations of MK
      2206 resulted in over 95 % of growth inhibition in all NPC cell lines with IC50
      values in the low micromolar range. Further experiments were performed in 3
      representative NPC cell lines: CNE-2 (harbor PIK3CA mutation and most sensitive
      to MK-2206), C666-1 (carries PIK3CA amplification), and HONE-1-EBV (least
      sensitive to MK-2206). MK-2206 induced G0/G1 cycle arrest in all 3 cell lines,
      but could induce apoptosis only in CNE-2 cells. MK-2206 significantly abrogated
      AKT signaling in all 3 cell lines by inhibiting the activation of AKT and its
      downstream effectors (FKHR, GSK3beta and BAD). MK-2206 also reduced mTOR
      signaling by reducing activation of mTOR and its downstream 4E-BP1 and p70S6
      kinase. MAPK activation was observed in HONE-1 and C666-1 cells, but not in CNE-2
      cells following exposure to MK-2206. The addition of MK-2206 to cisplatin (but
      not with paclitaxel) has a supra-additive inhibitory effect on growth in vitro.
      In summary, MK-2206 can inhibit growth and abrogate AKT and mTOR signaling in NPC
      cell lines. This agent is currently being evaluated in a phase II study in
      metastatic NPC.

PMID- 23143780
TI  - Combination with genistein enhances the efficacy of photodynamic therapy against
      human anaplastic thyroid cancer cells.
AB  - BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) has become one of the
      emerging options in management of cancer and other diseases. The major goal of
      PDT is to kill cancer cell without causing any adverse effect to the normal
      cells. PDT in combination of different therapeutic agents is being evaluated to
      improve the efficacy of treatment. Genistein, a soy ingredient, has widely been
      studied against different types of cancer. In the present study, combination of
      these two therapeutic methods has been studied to evaluate the enhanced
      effectiveness and find out the mechanism of action. MATERIALS AND METHODS:
      Combination of PDT and genistein has been studied against human thyroid cancer
      cells SNU 80. Cells were treated with genistein and different concentration of
      photofrin in PDT singly and conjointly. Viability of SNU 80 cells was analyzed
      using MTT assay. The cells were stained with Hoechst 33342 and propidium iodide
      (PI) for morphological observations. Changes in mitochondrial membrane potential
      and generation of reactive oxygen species (ROS) were also studied by confocal
      microscopy. Western blot analysis were also performed to find out the expressions
      of different pro- and anti-apoptotic proteins. RESULTS: From the result, the
      combination of genistein and photofrin mediated PDT enhanced the apoptotic effect
      against SNU 80 cells. Proliferation of the cells was inhibited and the
      mitochondrial membrane depolarisation was observed. ROS level were also increased
      in combination treatment. The expressions of Caspase 3, Caspase 9, cytochrome c,
      Caspase 8, Caspae 12 and other apoptosis related proteins were also modified.
      CONCLUSION: Thus PDT can induce apoptosis in thyroid cancer cells singly or in
      combination with genistein. But in combination treatment, the efficacy of
      inducing apoptosis in SNU 80 cells is much higher than that of individual
      treatment with genistein or PDT.

PMID- 23143781
TI  - Identification of distinct body mass index trajectories in Australian children.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Recent studies have identified distinct
      trajectories of obesity development in children, but more research is required to
      further explore these trajectories. Several socio-demographic variables such as
      parental education and obesity are associated with these trajectories. WHAT THIS
      STUDY ADDS: This study further demonstrates that there are distinct trajectories
      of body mass index in children. The use of raw body mass index values is more
      sensitive to changes in body composition compared with body mass index categories
      (e.g. lean vs. overweight). Hence the present results provide a more detailed
      insight into development patterns of obesity. The socio-demographic predictors of
      the trajectories offer potential avenues for future obesity interventions.
      BACKGROUND: A limited number of studies have demonstrated that there may be
      distinct developmental trajectories of obesity during childhood. OBJECTIVE: To
      identify distinct trajectories of body mass index (BMI) in a large sample of
      Australian children. METHODS: Participants included 4601 children aged 4-5 years
      at baseline, who were followed up at ages 6-7 years, 8-9 years and 10-11 years.
      Height and weight were measured at each of these time points, and used to
      calculate BMI. Growth Mixture Modelling was used to identify the presence of
      distinct BMI trajectories. RESULTS: Four distinct trajectories were identified
      (i) High Risk Overweight; (ii) Early Onset Overweight; (iii) Later Onset
      Overweight and (iv) Healthy Weight. Further analyses indicated that factors such
      as parental overweight, parent education, parent smoking and child birth weight
      were significant predictors of these trajectories. CONCLUSION: These findings
      indicate that different patterns of BMI development exist in children, which may
      require tailored interventions.

PMID- 23143782
TI  - Uniform polypyrrole nanoparticles with high photothermal conversion efficiency
      for photothermal ablation of cancer cells.
AB  - Uniform polypyrrole (PPy) nanoparticles are fabricated from a facile one-step
      aqueous dispersion polymerization. Owing to their high photothermal conversion
      efficiency and photostability compared with the well-known Au nanorods, as well
      as their good colloidal stability and biocompatibility, the resulting PPy
      nanoparticles can used as a novel promising photothermal ablation coupling agent
      for targeted treatment of cancer.

PMID- 23143783
TI  - Hemiconvulsion-hemiplegia-epilepsy syndrome with initially normal magnetic
      resonance imaging.

PMID- 23143784
TI  - Establishment of a family-centred care programme with follow-up home visits:
      implications for clinical care and economic characteristics.
AB  - BACKGROUND: Elternberatung Fruhstart is a family-centred care programme for very
      preterm infants and seriously ill neonates and their parents. The uniqueness of
      this programme is in its consistency and continuity in parental counselling from
      pregnancy at risk to follow-up home visits. PATIENTS AND METHODS: Family-centred
      care is provided by specialised nurses, a social education worker, a case
      manager, a psychologist and neonatologists. They give support and information to
      parents and facilitate transition to home including co-ordination of health care
      services and support networks. The programme starts with information for parents
      at risk of preterm delivery to lessen their anxieties and worries. After birth,
      parental bonding is encouraged and parents are involved in daily care procedures.
      The following weeks focus on communication, information and education in order to
      enhance parental competence. Discharge planning and coordinated follow-up visits
      involve the family doctor and several members of the welfare and health care
      system. One of the key objectives is to prevent re-hospitalisation. Over a 4 year
      period 330 families participated. Funding is provided by: 1) the hospital, from
      admission to discharge equivalent to one full-time nursing staff, 2) charity
      donations for follow-up visits and 3) health care insurance for social medical
      aftercare (Bunter Kreis) following S43, 2 SGB V in severe cases. RESULTS: As a
      result of this programme, the median length of stay was reduced by 24 days; the
      number of patients that stayed longer than average were reduced by 64% in the
      group of patients born < 1 500 g. At the same time the patient throughput
      increased from 243 to 413. CONCLUSION: To conclude, a family-centred care
      programme with coordinated follow-up increases parental satisfaction, reduces the
      length of the hospital stay and is therefore profitable.

PMID- 23143786
TI  - Photocatalytic conversion of diluted CO2 into light hydrocarbons using
      periodically modulated multiwalled nanotube arrays.

PMID- 23143785
TI  - Therapeutic roles of curcumin: lessons learned from clinical trials.
AB  - Extensive research over the past half century has shown that curcumin
      (diferuloylmethane), a component of the golden spice turmeric (Curcuma longa),
      can modulate multiple cell signaling pathways. Extensive clinical trials over the
      past quarter century have addressed the pharmacokinetics, safety, and efficacy of
      this nutraceutical against numerous diseases in humans. Some promising effects
      have been observed in patients with various pro-inflammatory diseases including
      cancer, cardiovascular disease, arthritis, uveitis, ulcerative proctitis, Crohn's
      disease, ulcerative colitis, irritable bowel disease, tropical pancreatitis,
      peptic ulcer, gastric ulcer, idiopathic orbital inflammatory pseudotumor, oral
      lichen planus, gastric inflammation, vitiligo, psoriasis, acute coronary
      syndrome, atherosclerosis, diabetes, diabetic nephropathy, diabetic
      microangiopathy, lupus nephritis, renal conditions, acquired immunodeficiency
      syndrome, beta-thalassemia, biliary dyskinesia, Dejerine-Sottas disease,
      cholecystitis, and chronic bacterial prostatitis. Curcumin has also shown
      protection against hepatic conditions, chronic arsenic exposure, and alcohol
      intoxication. Dose-escalating studies have indicated the safety of curcumin at
      doses as high as 12 g/day over 3 months. Curcumin's pleiotropic activities
      emanate from its ability to modulate numerous signaling molecules such as pro
      inflammatory cytokines, apoptotic proteins, NF-kappaB, cyclooxygenase-2, 5-LOX,
      STAT3, C-reactive protein, prostaglandin E(2), prostate-specific antigen,
      adhesion molecules, phosphorylase kinase, transforming growth factor-beta,
      triglyceride, ET-1, creatinine, HO-1, AST, and ALT in human participants. In
      clinical trials, curcumin has been used either alone or in combination with other
      agents. Various formulations of curcumin, including nanoparticles, liposomal
      encapsulation, emulsions, capsules, tablets, and powder, have been examined. In
      this review, we discuss in detail the various human diseases in which the effect
      of curcumin has been investigated.

PMID- 23143787
TI  - Genomic characterisation of a lentogenic Newcastle disease virus strain HX01
      isolated from sick pigs in China.
AB  - This paper describes the complete genome sequence of HX01, an isolate of the
      Newcastle disease virus (NDV) collected from a swine disease outbreak. The genome
      is 15,186 nt long and consists of six genes in the order of 3'-NP-P-M-F-HN-L-5'.
      This genome has the same length as the old NDV genotypes (I-IV), whereas the new
      NDV genotypes (V-IX) are 15,192 nt long. Compared with the genomic sequences of
      the reference NDV strains, the HX01 genome is highly similar to the genome of
      other NDV strains. However, some unique features of the HN gene were found in
      HX01. HX01 possesses the motif (112)G-R-Q-G-R-L(117) at the fusion protein
      cleavage site, which is typical of lentogenic strains. Pathogenicity tests based
      on the mean death time and the intracerebral pathogenicity index also revealed
      the isolate's lentogenic character. Phylogenetic analysis based on the variable
      region of the F gene (nt 47-420) revealed that HX01 was clustered to genotype II
      within class II NDV. Genetically, HX01 has a high similarity with the La Sota
      vaccine strain based on the single gene or complete genomic but is far different
      from the prevalent genotype VIId NDV which circulates in fowls and waterfowls in
      mainland China.

PMID- 23143788
TI  - Generic medications in ophthalmology.
AB  - The purpose of this review is to discuss the process of genericisation of
      medications in the US and Europe with a focus on ophthalmic drugs. Regulatory
      guidelines of the US Food and Drug Administration and the European Medicines
      Agency will be discussed, and the advantages and concerns of genericisation will
      be explored. We will look at various studies concerning the safety and efficacy
      of generic drugs compared to their branded counterparts. In particular, the
      challenges of assuring bioequivalence and therapeutic equivalence in topical
      ophthalmic drugs will be examined.

PMID- 23143790
TI  - Hyperocclusion up-regulates CCL3 expression in CCL2- and CCR2-deficient mice.
AB  - Excessive mechanical stress (MS) during hyperocclusion is known to result in
      disappearance of the alveolar hard line, enlargement of the periodontal ligament
      (PDL) space, and destruction of alveolar bone, leading to occlusal traumatism. We
      have recently reported that MS induces predominantly C-C chemokine ligand (CCL) 2
      expression in PDL tissues, leading, via C-C chemokine receptor (CCR) 2, to MS
      dependent osteoclastogenesis in alveolar bone. Thus, we hypothesize that ablation
      of the CCL2/CCR2 signaling pathway should suppress MS-induced osteoclastogenesis
      associated chemokines and alleviate occlusal traumatism. We examined the effect
      of MS on chemokine expression and osteoclastogenesis using in vivo and in vitro
      hyperocclusion models with CCL2-deficient (CCL2((-/-))) and CCR2-deficient
      (CCR2((-/-))) mice. Compared with that in wild-type mice, expression of CCL3 in
      PDL cells and TRAP-positive cells in alveolar bone from CCL2((-/-)) and CCR2((-/
      )) mice was up-regulated, even in the absence of MS. Furthermore, the expression
      of CCL3 and TRAP-positive cells was significantly increased after both 4 and 7
      days of hyperocclusal MS loading in CCL2((-/-)) and CCR2((-/-)) mice.
      Hyperocclusion induced compensatory CCL3 expression and promoted
      osteoclastogenesis to counterbalance deficient CCL2/CCR2 signaling, suggesting
      that co-expression of CCL3 with CCL2 may precipitate synergistic, MS-dependent
      alveolar bone destruction during occlusal traumatism. ABBREVIATIONS: MS,
      mechanical stress; PDL, periodontal ligament; CCL2, CC chemokine ligand 2 (MCP-1;
      monocyte chemoattractant protein-1); CCR2, CC chemokine receptor 2; CCL3, CC
      chemokine ligand 3 (MIP-1alpha); CCL5, CC chemokine ligand 5 (RANTES).

PMID- 23143791
TI  - Lung cancer resection rate is related to survival.

PMID- 23143792
TI  - Longitudinal association between lung function and health-related quality of life
      in cystic fibrosis.
AB  - BACKGROUND: Lung function is an important indicator of cystic fibrosis disease
      status and those with better forced expiratory volume in 1 s (FEV(1))% predicted
      have tended to report a better health-related quality of life (HRQoL) in cross
      sectional studies. The relationship between lung function and HRQoL over time is
      unknown. This work assesses the natural progression of HRQoL reporting over many
      years and compares assessments across a whole decade and evaluates the
      relationship between lung function and HRQoL longitudinally. METHODS: Demographic
      (age, gender), clinical (FEV(1)% predicted, body mass index, diabetes,
      Burkholderia cepacia complex, intravenous access device and nutritional status)
      and HRQoL (Cystic Fibrosis Quality of Life Questionnaire) variables were obtained
      every 2 years over a 12-year period (seven time points from 1998 to 2010).
      RESULTS: HRQoL and lung function declined slowly over time and significant decade
      changes were observed for FEV(1)% predicted and the nine domains of the Cystic
      Fibrosis Quality of Life Questionnaire. The results of random coefficient
      modelling indicated that, at the population level, decreasing FEV(1)% predicted
      was associated with decreasing HRQoL after adjusting for confounding variables.
      However, the percentage of patients for whom a decrease in lung function was
      associated with a decrease in HRQoL differed according to the quality of life
      domain. CONCLUSIONS: HRQoL and FEV(1)% predicted decline slowly; nevertheless, a
      decrease in lung function predicted a decrease in HRQoL over time.

PMID- 23143793
TI  - Critical role of fractalkine (CX3CL1) in cigarette smoke-induced mononuclear cell
      adhesion to the arterial endothelium.
AB  - BACKGROUND: Cigarette smoking is an important risk factor for the development of
      cardiovascular disease, yet the pathways through which this may operate are
      poorly understood. Therefore, the mechanism underlying cigarette smoke (CS)
      induced arterial endothelial dysfunction and the potential link with
      fractalkine/CX(3)CL1 upregulation were investigated. METHODS AND RESULTS:
      Stimulation of human arterial umbilical endothelial cells (HUAECs) with
      pathophysiological concentrations of CS extract (1% CSE) increased CX(3)CL1
      expression. Neutralisation of CX(3)CL1 activity under dynamic flow conditions
      significantly inhibited CSE-induced mononuclear cell adhesion to HUAECs (67%).
      The use of small interfering RNA (siRNA) revealed that nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidase 5 (Nox5) but not Nox2 or Nox4 is the main
      NADPH isoform involved in CSE-induced CX(3)CL1 upregulation and mononuclear cell
      arrest. Knock down of HUAEC tumour necrosis factor alpha expression with siRNA or
      pharmacological inhibition of p38 mitogen-activated protein kinase and nuclear
      factor kappaB also abolished these responses. Interestingly, circulating
      monocytes and lymphocytes from patients with chronic obstructive pulmonary
      disease (COPD) (n=29) versus age-matched controls (n=23) showed
      CX(3)CR1overexpression. Furthermore, CX(3)CL1 neutralisation dramatically
      diminished their enhanced adhesiveness to CSE-stimulated HUAECs. Finally, when
      animals were exposed for 3 days to CS, a mild inflammatory response in the lung
      was observed which was accompanied by enhanced CX(3)CL1 expression in the
      cremasteric arterioles, an organ distant from the lung. CS exposure resulted in
      increased leukocyte-arteriolar endothelial cell adhesion which was significantly
      reduced (51%) in animals lacking CX(3)CL1 receptor (CX(3)CR1). CONCLUSIONS: These
      results suggest that CS induces functional CX(3)CL1 expression in arterial
      endothelium and leukocytes from patients with COPD show increased CX(3)CL1
      dependent adhesiveness. Therefore, targeting the CX(3)CL1/CX(3)CR1 axis might
      prevent COPD-associated cardiovascular disorders.

PMID- 23143794
TI  - Relationship of circulating matrix biomarkers to myocardial matrix metabolism in
      advanced heart failure.
AB  - AIMS: Interstitial fibrosis is a key component of myocardial remodelling in heart
      failure (HF). Many studies have measured peripheral blood levels of procollagens
      and matrix metalloproteinases (MMPs), as a surrogate for myocardial matrix
      metabolism, particularly to evaluate the effect of interventions and their
      prognostic relevance. However, the relationship between peripheral biomarker
      levels and actual cardiac turnover in HF is not known. We aimed to determine
      whether peripheral levels of relevant biomarkers reflect cardiac release in
      patients with advanced HF. METHODS AND RESULTS: We determined whether the failing
      human heart releases collagen precursors [procollagen I N-terminal peptide (PINP)
      and procollagen III N-terminal peptide (PIIINP)], or key matrix
      metalloproteinases (MMP9) and MMP inhibitors [tissue inhibitor of
      metalloproteinase 1 (TIMP1)] by performing transcardiac blood sampling in healthy
      controls (n = 9) and in patients with advanced HF (n = 18, left ventricular
      ejection fraction 22 +/- 2%). HF patients had higher arterial levels of PIIINP
      compared with controls (7.0 +/- 0.7 vs. 4.0 +/- 0.2 ug/L, P < 0.001). PIIINP was
      closely correlated with the pulmonary capillary wedge pressure (r = 0.54, P =
      0.01) and the estimated glomerular filtration rate (r = -0.50, P = 0.01).
      Transcardiac blood sampling demonstrated that there was no net release of either
      PINP or PIIINP in controls or HF patients. The transcardiac MMP9 gradient was
      significantly lower in HF patients (P < 0.05), and was negatively correlated with
      left ventricular mass (r = -0.51, P = 0.01). CONCLUSIONS: Our study shows that
      the concentration of circulating levels of PINP, PIIINP, MMP9, and TIMP1 do not
      accurately reflect cardiac turnover. This study highlights the importance of
      performing transcardiac blood sampling to validate the utility of emerging
      cardiac biomarkers.

PMID- 23143795
TI  - Heart failure determines the myocardial inflammatory response to injury.
AB  - AIMS: Systemic complications after cardiac surgery are common in heart failure
      patients. However, the pathophysiological mechanisms, such as a different local
      inflammatory response of failing hearts, remain in question. This study examines
      whether failing hearts respond differently to cardioplegic arrest and reperfusion
      compared with non-failing hearts (controls). METHODS AND RESULTS: The
      inflammatory response was evaluated in samples collected simultaneously from the
      radial artery and coronary sinus, and myocardial tissue in 62 patients undergoing
      cardiac surgery. No myocardial release of inflammatory mediators was observed
      upon reperfusion in controls (n = 19). In contrast, in patients with heart
      failure, reperfusion was characterized by a myocardial release of several
      cytokines. Myocardial interleukin-6 was 115% increased in non-ischaemic heart
      failure (n = 18, P = 0.002) as compared with a 117% increase in patients with
      ischaemic heart failure (n = 25, P = 0.01). Furthermore, a myocardial release of
      monocyte chemoattractant protein-1 was observed in both patient groups: a 109% (P
      = 0.001) and 114% (P = 0.01) increase in patients with non-ischaemic heart
      failure and ischaemic heart failure, respectively. Post-operative myocardial
      damage, expression of inflammatory mediators, and p65-nuclear factor-kappaB
      activity were similar in all patient groups. Inflammatory cell content was
      increased in early ischaemic myocardial tissue in both heart failure groups
      compared with controls. CONCLUSION: Heart failure patients show a clear
      myocardial inflammatory response upon reperfusion, probably explained by
      degranulation of infiltrated inflammatory cells. Results in controls indicate
      that they better withstand cardioplegic arrest and reperfusion without an
      explicit myocardial inflammatory response.

PMID- 23143796
TI  - Updated meta-analysis on antithrombotic therapy in patients with heart failure
      and sinus rhythm.
AB  - AIM: Heart failure (HF) is a prothrombotic state, but current evidence does not
      support the routine use of aspirin, antiplatelet agents, or anticoagulation in
      these patients in sinus rhythm (SR). We conducted an updated meta-analysis
      comparing these medications on outcomes in HF. METHODS AND RESULTS: All
      randomized trials in patients with chronic HF and reduced ejection fraction
      (HFREF) in sinus rhythm (SR; n >100), in which the effect of aspirin,
      antiplatelet agents, or anticoagulants was determined, were prospectively
      evaluated. Four trials met the entry criteria. Intervention time was 28 months.
      No difference in all-cause mortality was seen when aspirin was compared with
      warfarin [n = 3701, relative risk (RR) 1.00, 95% confidence interval (CI) 0.88
      1.13, P = 0.94]. Compared with aspirin, significantly fewer strokes were seen
      with warfarin (n = 3701, RR 0.59, 95% CI 0.41-0.85, P = 0.004), and fewer fatal
      and non-fatal ischaemic strokes (n = 3368, RR 0.48, 95% CI 0.32-0.73, P =
      0.0006). Warfarin doubled the risk of major haemorrhage compared with aspirin (n
      = 3701, RR 2.02, 95% CI 1.45-2.80, P < 0.0001); however, intracranial haemorrhage
      was rare. There was no significant difference in HF hospitalizations with aspirin
      vs. warfarin (n = 3701, RR 1.16, 95% CI 0.79-1.71, P = 0.45). CONCLUSION: With
      warfarin compared with aspirin in HFREF in SR, significant reductions in stroke
      risk were observed but no mortality benefit was seen. Major haemorrhage doubled
      but intracranial haemorrhage was rare. These findings suggest that overall the
      benefit of warfarin in HFREF in SR outweighs the risk. Aspirin use did not
      increase HF hospitalization as has been previously suggested.

PMID- 23143797
TI  - Solvatochromism and nonradiative decay of intramolecular charge-transfer excited
      states: bands-of-energy model, thermodynamics, and self-organization.
AB  - The fluctuations of orientation and induction interactions in solution and their
      impact on the broadening of absorption and fluorescence spectra are considered in
      terms of a bands-of-energy model. Also covered is the application of principles
      of thermodynamics and self-organization of systems for calculation of
      solvatochromic shift, among them a component owing to the work on electronic
      polarization of solvent at the instant of electronic transition in the solute.
      The findings on solvatochromic shift and spectral broadening open the way to the
      calculation of solvent effects on the rate constant of nonradiative transitions.
      As demonstrated herein for 15 fluorophores, the novel theory of nonradiative
      decay of the intramolecular charge-transfer excited states is carried out for
      dyes and organic compounds of different nature, both for polar and nonpolar
      media.

PMID- 23143798
TI  - Microstructure, mechanical property, corrosion behavior, and in vitro
      biocompatibility of Zr-Mo alloys.
AB  - In this study, the microstructure, mechanical properties, corrosion behaviors,
      and in vitro biocompatibility of Zr-Mo alloys as a function of Mo content after
      solution treatment were systemically investigated to assess their potential use
      in biomedical application. The experimental results indicated that Zr-1Mo alloy
      mainly consisted of an acicular structure of alpha' phase, while omega phase
      formed in Zr-3Mo alloy. In Zr-5Mo alloy, retained beta phase and a small amount
      of precipitated alpha phase were observed. Only the retained beta phase was
      obtained in Zr-10Mo alloy. Zr-1Mo alloy exhibited the greatest hardness, bending
      strength, and modulus among all experimental Zr-Mo alloys, while beta phase Zr
      10Mo alloy had a low modulus. The results of electrochemical corrosion indicated
      that adding Mo into Zr improved its corrosion resistance which resulted in
      increasing the thermodynamic stability and passivity of zirconium. The
      cytotoxicity test suggested that the extracts of the studied Zr-Mo alloys
      produced no significant deleterious effect to fibroblast cells (L-929) and
      osteoblast cells (MG 63), indicating an excellent in vitro biocompatibility.
      Based on these facts, certain Zr-Mo alloys potentially suitable for different
      biomedical applications were proposed.

PMID- 23143799
TI  - Transcriptional response of mucoid Pseudomonas aeruginosa to human respiratory
      mucus.
AB  - Adaptation of bacterial pathogens to a host can lead to the selection and
      accumulation of specific mutations in their genomes with profound effects on the
      overall physiology and virulence of the organisms. The opportunistic pathogen
      Pseudomonas aeruginosa is capable of colonizing the respiratory tract of
      individuals with cystic fibrosis (CF), where it undergoes evolution to optimize
      survival as a persistent chronic human colonizer. The transcriptome of a host
      adapted, alginate-overproducing isolate from a CF patient was determined
      following growth of the bacteria in the presence of human respiratory mucus. This
      stable mucoid strain responded to a number of regulatory inputs from the mucus,
      resulting in an unexpected repression of alginate production. Mucus in the medium
      also induced the production of catalases and additional peroxide-detoxifying
      enzymes and caused reorganization of pathways of energy generation. A specific
      antibacterial type VI secretion system was also induced in mucus-grown cells.
      Finally, a group of small regulatory RNAs was identified and a fraction of these
      were mucus regulated. This report provides a snapshot of responses in a pathogen
      adapted to a human host through assimilation of regulatory signals from tissues,
      optimizing its long-term survival potential. IMPORTANCE: The basis for chronic
      colonization of patients with cystic fibrosis (CF) by the opportunistic pathogen
      Pseudomonas aeruginosa continues to represent a challenging problem for basic
      scientists and clinicians. In this study, the host-adapted, alginate
      overproducing Pseudomonas aeruginosa 2192 strain was used to assess the changes
      in its transcript levels following growth in respiratory CF mucus. Several
      significant and unexpected discoveries were made: (i) although the alginate
      overproduction in strain 2192 was caused by a stable mutation, a mucus-derived
      signal caused reduction in the transcript levels of alginate biosynthetic genes;
      (ii) mucus activated the expression of the type VI secretion system, a mechanism
      for killing of other bacteria in a mixed population; (iii) expression of a number
      of genes involved in respiration was altered; and (iv) several small regulatory
      RNAs were identified, some being mucus regulated. This work highlights the strong
      influence of the host environment in shaping bacterial survival strategies.

PMID- 23143800
TI  - Antibiotic-mediated selection of quorum-sensing-negative Staphylococcus aureus.
AB  - Staphylococcus aureus is a human commensal that at times turns into a serious
      bacterial pathogen causing life-threatening infections. For the delicate control
      of virulence, S. aureus employs the agr quorum-sensing system that, via the
      intracellular effector molecule RNAIII, regulates virulence gene expression. We
      demonstrate that the presence of the agr locus imposes a fitness cost on S.
      aureus that is mediated by the expression of RNAIII. Further, we show that
      exposure to sublethal levels of the antibiotics ciprofloxacin, mupirocin, and
      rifampin, each targeting separate cellular functions, markedly increases the agr
      mediated fitness cost by inducing the expression of RNAIII. Thus, the extensive
      use of antibiotics in hospitals may explain why agr-negative variants are
      frequently isolated from hospital-acquired S. aureus infections but rarely found
      among community-acquired S. aureus strains. Importantly, agr deficiency
      correlates with increased duration of and mortality due to bacteremia during
      antibiotic treatment and with a higher frequency of glycopeptide resistance than
      in agr-carrying strains. Our results provide an explanation for the frequent
      isolation of agr-defective strains from hospital-acquired S. aureus infections
      and suggest that the adaptability of S. aureus to antibiotics involves the agr
      locus. IMPORTANCE: Staphylococcus aureus is the most frequently isolated pathogen
      in intensive care units and a common cause of nosocomial infections, resulting in
      a high degree of morbidity and mortality. Surprisingly, a large fraction (15 to
      60%) of hospital-isolated S. aureus strains are agr defective and lack the main
      quorum-sensing-controlled virulence regulatory system. This is a problem, as agr
      defective strains are associated with a mortality level in bacteremic infections
      and a probability of glycopeptide resistance greater than those of other strains.
      We show here that agr-negative strains have a fitness advantage over agr-positive
      strains in the presence of sublethal concentrations of some antibiotics and that
      the fitness defect of agr-positive cells is caused by antibiotic-mediated
      expression of the agr effector molecule RNAIII. These results offer an
      explanation of the frequent isolation of agr-defective S. aureus strains in
      hospitals and will influence how we treat S. aureus infections.

PMID- 23143801
TI  - Variation in selenoenzyme genes and prostate cancer risk and survival.
AB  - BACKGROUND: While several studies showed that selenium may prevent prostate
      cancer (PCa), few studies have evaluated variation in selenoenzyme genes in
      relation to PCa risk and survival. METHODS: We studied common variants in seven
      selenoenzymes genes in relation to risk of PCa and PCa-specific mortality (PCSM).
      In a population-based case-control study of men of European ancestry (1,309
      cases, 1,266 controls), we evaluated 35 common, tagging single nucleotide
      polymorphisms (SNPs) in GPX1 (n = 2), GPX2 (n = 4), GPX3 (n = 6), GPX4 (n = 6),
      SEP15 (n = 4), SEPP1 (n = 6), and TXNRD1 (n = 7) in relation to PCa risk, and
      among cases, associations between these variants and risk of PCSM. We used
      logistic regression and Cox proportional hazards regression to estimate the
      relative risk of PCa and PCSM, respectively. RESULTS: Of the SNPs examined, only
      GPX1 rs3448 was associated with overall PCa risk with an odds ratio of 0.62 for
      TT versus CC (95% confidence interval, 0.44-0.88). SNPs in GPX2, GPX3, GPX4,
      SEP15, and SEPP1 had different risk estimates for PCa in subgroups based on stage
      and grade. We observed associations between SNPs in GPX4, and TXNRD1 and risk of
      PCSM. None of these associations, however, remained significant after adjustment
      for multiple comparisons. CONCLUSIONS: We found evidence that genetic variation
      in a subset of selenoenzyme genes may alter risk of PCa and PCSM. These results
      need validation in additional subsets.

PMID- 23143802
TI  - Thyroid disruption in the lizard Podarcis bocagei exposed to a mixture of
      herbicides: a field study.
AB  - Pesticide exposure has been related with thyroid disrupting effects in different
      vertebrate species. However, very little is known about the effects of these
      compounds in reptiles. In the Mediterranean area, lacertid lizards are the most
      abundant vertebrate group in agroecosystems, and have been identified as
      potential model species for reptile ecotoxicology. The aim of this study was to
      understand if the herbicides applied in corn fields have thyroid disruptive
      effects in the lizard Podarcis bocagei. Adult male lizards were captured in north
      western Portugal in corn fields treated with herbicides (exposed sites), and in
      organic agricultural fields (reference sites). Thyroid and male gonad morphology
      and functionality, and testosterone levels were investigated through
      histological, immunohistochemical and biochemical techniques. Lizards from
      exposed locations displayed thyroid follicular lumens with more reabsorption
      vacuoles and significantly larger follicular area than those from reference
      fields. Furthermore, testes of lizards from exposed locations had significantly
      larger seminiferous tubule diameters, significantly higher number of
      spermatogenic layers and displayed an up-regulation of thyroid hormone receptors
      when compared with lizards from reference areas. These findings strongly suggest
      that the complex mixture of herbicides that lizards are exposed to in
      agricultural areas have thyroid disrupting effects which ultimately affect the
      male reproductive system. Alachlor, which has demonstrated thyroid effects in
      mammals, may be largely responsible for the observed effects.

PMID- 23143803
TI  - Effects of pyrene exposure and temperature on early development of two co
      existing Arctic copepods.
AB  - Oil exploration is expected to increase in the near future in Western Greenland.
      At present, effects of exposure to oil compounds on early life-stages of the
      ecologically important Calanus spp. are unknown. We investigated the effects of
      the oil compound pyrene, on egg hatching and naupliar development of the calanoid
      copepods Calanus glacialis and C. finmarchicus, two key species in the Disko Bay,
      Western Greenland. At low temperature the nauplii of C. glacialis experienced
      reduced growth when exposed to pyrene, and survival in both species decreased.
      Naupliar mortality increased with temperature at high pyrene concentration in C.
      finmarchicus. Both Calanus species were affected by pyrene exposure but C.
      finmarchicus was more sensitive compared to C. glacialis. Lowered growth rate and
      increased mortality of the naupliar stages entail reduced recruitment to copepod
      populations. Exposure to pyrene from an oil spill may reduce the standing stock
      of Calanus, which can lead to less energy available to higher trophic levels in
      the Arctic marine food web.

PMID- 23143804
TI  - [Transoral robotic surgery for head and neck tumors: a series of 17 patients].
AB  - BACKGROUND: Within the last years transoral robotic surgery (TORS) has gained
      importance in the resection of head and neck tumors, especially in North America.
      In contrast only few groups in Germany have studied this system so far. In
      respect to potential future developments in surgical robotic systems it seems
      reasonable to deal with this system. MATERIAL AND METHODS: 17 patients with
      tumors of the oropharynx, the base of tongue or the supraglottic area were
      treated with TORS in our clinic, between May 2011 and June 2012. In a prospective
      study we analyzed the exposure, visualization and resectability of these tumors
      using the da Vinci-system. In addition, set up and operation time, as well as
      costs were evaluated. RESULTS: All neoplasms of the oropharynx (n=9) and the
      tongue base (n=5) could be well exposed, visualized and resected. In the
      supraglottic area (n=3) 2 tumors could not be properly exposed and therefore
      resection was converted to a transoral microscopic laser approach. Resection with
      the cautery spatula tip or the Tm:YAG-laser fibre caused wide coagulation zones,
      but resulted in good hemostasis. The costs for the medical equipment and the
      leasing rate were 6280 ? per case at our institution. CONCLUSION: Tumors of the
      tongue base and oropharynx could be easily visualized with help of the da Vinci
      system. The resection of supraglottic tumors can be challenging, due to the
      arrangement of the robotic-arms and the narrow anatomic conditions. Despite its
      high costs, the da Vinci-system is a potentially interesting supplementation to
      existing surgical techniques.

PMID- 23143805
TI  - Three-dimensional visualization of defects formed during the synthesis of metal
      organic frameworks: a fluorescence microscopy study.
AB  - Imperfections in the spotlight: fluorescence microscopy was used to detect
      defects in metal-organic frameworks formed during synthesis. In contrast to
      currently available techniques, confocal fluorescence microscopy offers the
      advantage of three-dimensional imaging at the single-crystal level combined with
      the sensitivity required to study the start of defect formation.

PMID- 23143806
TI  - Xenon neuroprotection in experimental stroke: interactions with hypothermia and
      intracerebral hemorrhage.
AB  - BACKGROUND: Xenon has been proven to be neuroprotective in experimental brain
      injury. The authors hypothesized that xenon would improve outcome from focal
      cerebral ischemia with a delayed treatment onset and prolonged recovery interval.
      METHODS: Rats were subjected to 70 min temporary focal ischemia. Ninety minutes
      later, rats were treated with 0, 15, 30, or 45% Xe for 20 h or 0 or 30% Xe for 8,
      20, or 44 h. Outcome was measured after 7 days. In another experiment, after
      ischemia, rats were maintained at 37.5 degrees  or 36.0 degrees C for 20 h with
      or without 30% Xe. Outcome was assessed 28 days later. Finally, mice were
      subjected to intracerebral hemorrhage with or without 30% Xe for 20 h. Brain
      water content, hematoma volume, rotarod function, and microglial activation were
      measured. RESULTS: Cerebral infarct sizes (mean+/-SD) for 0, 15, 30, and 45% Xe
      were 212+/-27, 176+/-55, 160+/-32, and 198+/-54 mm, respectively (P=0.023).
      Neurologic scores (median+/-interquartile range) followed a similar pattern
      (P=0.002). Infarct size did not vary with treatment duration, but neurologic
      score improved (P=0.002) at all xenon exposure durations (8, 20, and 44 h).
      Postischemic treatment with either 30% Xe or subtherapeutic hypothermia (36
      degrees C) had no effect on 28-day outcome. Combination of these interventions
      provided long-term benefit. Xenon improved intracerebral hemorrhage outcome
      measures. CONCLUSION: Xenon improved focal ischemic outcome at 7, but not 28 days
      postischemia. Xenon combined with subtherapeutic hypothermia produced sustained
      recovery benefit. Xenon improved intracerebral hemorrhage outcome. Xenon may have
      potential for clinical stroke therapy under carefully defined conditions.

PMID- 23143808
TI  - Human mitochondrial DNA replication.
AB  - Elucidation of the process of DNA replication in mitochondria is in its infancy.
      For many years, maintenance of the mitochondrial genome was regarded as greatly
      simplified compared to the nucleus. Mammalian mitochondria were reported to lack
      all DNA repair systems, to eschew DNA recombination, and to possess but a single
      DNA polymerase, polymerase gamma. Polgamma was said to replicate mitochondrial
      DNA exclusively via one mechanism, involving only two priming events and a
      handful of proteins. In this "strand-displacement model," leading strand DNA
      synthesis begins at a specific site and advances approximately two-thirds of the
      way around the molecule before DNA synthesis is initiated on the "lagging"
      strand. Although the displaced strand was long-held to be coated with protein,
      RNA has more recently been proposed in its place. Furthermore, mitochondrial DNA
      molecules with all the features of products of conventional bidirectional
      replication have been documented, suggesting that the process and regulation of
      replication in mitochondria is complex, as befits a genome that is a core factor
      in human health and longevity.

PMID- 23143809
TI  - Reduced administered activity, reduced acquisition time, and preserved image
      quality for the new CZT camera.
AB  - BACKGROUND: For a 1-day myocardial perfusion SPECT (MPS) the recommendations for
      administered activity stated in the EANM guidelines results in an effective dose
      of up to 16 mSv per patient. Recently, a gamma camera system, based on cadmium
      zinc telluride (CZT) technology, was introduced. This technique has the potential
      to reduce the effective dose and scan time compared to the conventional NaI gamma
      camera. The aim of this study was to investigate if the effective dose can be
      reduced with a preserved image quality using CZT technology in MPS. METHODS: In
      total, 150 patients were included in the study. All underwent a 1-day (99m)Tc
      tetrofosmin stress-rest protocol and were divided into three subgroups (n = 50 in
      each group) with 4, 3, and 2.5 MBq/kg body weight of administered activity in the
      stress examination, respectively. The acquisition time was increased in
      proportion to the decrease in administered activity. All examinations were
      analyzed for image quality by visual grading on a 4-point scale (1 = poor, 2 =
      adequate, 3 = good, 4 = excellent), by two expert readers. RESULTS: The total
      effective dose (stress + rest) decreased from 9.3 to 5.8 mSv comparing 4 to 2.5
      MBq/kg body weight. For the patients undergoing stress examination only (35%) the
      effective dose, administrating 2.5 MBq/kg, was 1.4 mSv. The image acquisition
      times for 2.5 MBq/kg body weight were 475 and 300 seconds (stress and rest)
      compared to 900 seconds for each when using conventional MPS. The average image
      quality was 3.7 +/- 0.5, 3.8 +/- 0.5, and 3.8 +/- 0.4 for the stress images and
      3.5 +/- 0.6, 3.6 +/- 0.6, and 3.5 +/- 0.6 for the rest images and showed no
      statistically significant difference (P = .62) among the 4, 3, and 2.5 MBq/kg
      groups. CONCLUSIONS: The new CZT technology can be used to considerably decrease
      the effective dose and acquisition time for MPS with preserved high image
      quality.

PMID- 23143810
TI  - Quantification of myocardial area at risk in the absence of collateral flow: the
      validation of angiographic scores by myocardial perfusion single-photon emission
      computed tomography.
AB  - OBJECTIVES: Our study aimed to compare the area at risk (AAR) determined by
      single-photon emission computed tomography (SPECT) with the Bypass Angioplasty
      Revascularization Investigation (BARI) and modified Alberta Provincial Project
      for Outcome Assessment in Coronary Heart Disease (APPROACH) angiographic scores
      in the setting of patients undergoing coronary angioplasty for either unstable
      angina or an STEMI. BACKGROUND: Radionuclide myocardial perfusion imaging prior
      to reperfusion has classically been the most widely practised technique for
      assessing the AAR and has been successfully used to compare the efficacy of
      various reperfusion strategies in patients with an ST-segment elevation
      myocardial infarction (STEMI). The BARI and modified APPROACH scores are
      angiographic methods widely used to provide a rapid estimation of the AAR;
      however, they have not been directly validated with myocardial perfusion single
      photon emission computed tomography (SPECT). METHODS: Fifty-five patients with no
      previous myocardial infarction who underwent coronary angioplasty for single
      vessel disease (unstable angina: n = 25 or an STEMI: n = 30) with no evidence of
      collaterals (Rentrop Collateral Score <2) were included in a prospective study.
      In STEMI patients, the (99m)Tc-tetrofosmin was injected prior to opening of the
      occluded vessel and, in patients with unstable angina after 10-15 seconds of
      balloon inflation. Acquisition was performed with a dual-head gammacamera with a
      low-energy and high-resolution collimator. A total of 60 projections were
      acquired using a non-circular orbit. No attenuation or scatter correction was
      used. Maximal contours of hypoperfusion regions corresponding to each coronary
      artery occlusion were delineated over a polar map of 17 segments and compared
      with the estimated AAR determined by two experienced interventional cardiologists
      using both angiographic scores. RESULTS: Mean AAR percentage in SPECT was 35.0
      (10.0%-56.0%). A high correlation was found between BARI and APPROACH scores (r =
      0.9, P < .001). Furthermore, a high correlation was also observed between BARI
      versus SPECT and APPROACH versus SPECT to estimate the AAR (r = 0.9, P < .001 and
      r = 0.8, P < .001, respectively). Better correlations were observed when the left
      anterior descending artery (LAD) was revascularized (r = 0.8, P < 0.001 with
      BARI; r = 0.8, P = .001 with APPROACH) compared to other territories (r = 0.8, P
      = .001 with BARI; r = 0.7, P = .001 with APPROACH). Also, better correlations
      were observed in patients who underwent an elective rather than a primary
      percutaneous revascularization procedure. CONCLUSIONS: In the absence of
      collateral flow, BARI and APPROACH scores constitute valid methods for AAR
      estimation in current clinical practice, with more accurate results when used for
      the LAD territory; both are useful not only in STEMI patients but also in
      patients with unstable angina.

PMID- 23143811
TI  - Off-label, but on-target: use of regadenoson with exercise.

PMID- 23143812
TI  - Dual-responsive gold nanoparticles for colorimetric recognition and testing of
      carbohydrates with a dispersion-dominated chromogenic process.
AB  - A dispersion-dominated colorimetric approach for the recognition of carbohydrates
      based on biomolecule-responsive AuNPs is presented. Taking advantage of the
      unique dual-responsiveness of smart copolymers, the aggregation and dispersion of
      AuNPs can be modulated by both temperature and different kinds of carbohydrates,
      giving rise to a novel chromogenic mechanism for the recognition and testing of
      carbohydrates in aqueous media.

PMID- 23143813
TI  - The protective effects of Prunus armeniaca L (apricot) against methotrexate
      induced oxidative damage and apoptosis in rat kidney.
AB  - This study was conducted to evaluate a possible protective role of apricot in
      apoptotic cell death induced by methotrexate (MTX) and renal damage by different
      histological and biochemical parameters. Twenty-eight rats were divided into four
      groups, control, apricot, methotrexate, and apricot + methotrexate. Methotrexate
      induced renal failure, as shown by significant serum creatinine and urea
      elevation. Additionally, the results indicated that methotrexate significantly
      induced lipid peroxidation and reduced antioxidant activities in rats. In
      contrast, apricot significantly prevented toxic effects of methotrexate via
      increased catalase, superoxide dismutase, and glutathione levels but decreased
      formation of malondialdehyde. Also, it was determined that exposure to
      methotrexate leads to significant histological damage in kidney tissue such as
      glomerulosclerosis and apoptosis. On the other hand, these effects can be
      eliminated with apricot diet. These data indicate that apricot may be useful in
      preventing undesirable effects of MTX such as nephrotoxicity. 

PMID- 23143814
TI  - Scar asymmetry after abdominoplasty: the unexpected role of seroma.
AB  - Achievement of symmetry remains one of the goals of cosmetic procedures.
      Interestingly, scar asymmetry after abdominoplasty has been rarely considered a
      complication. However, this can have a significant impact on patient and surgeon
      satisfaction. This study identifies silent seromas as a potential cause of scar
      asymmetry.Among abdominoplasty procedures in a university hospital institution
      over a 30 months' period (October 1, 2007 to April 1, 2010), we retrospectively
      identified 6 patients who developed abdominal scar asymmetry only 3 months
      postoperatively and without any early warning complications (hematoma, seroma, or
      infection). Clinical examination was completed by abdominal diagnostic
      ultrasonography. Seroma capsulectomy under local anesthesia was performed in all
      cases.In all patients clinically presenting late abdominal scar asymmetry,
      ultrasonography confirmed the presence of an encapsulated chronic seroma.
      Surgical capsulectomy under local anesthesia resulted in reestablishment of
      former symmetry and high patient satisfaction. No complications such as wound
      infection, dehiscence, hematoma, or recurrence of seroma were detected after
      revision surgery.In our experience, fibrous capsule due to chronic seromas
      resulted in abdominal scar deviation and asymmetry. Surgical capsulectomy
      followed by wearing of compressive garments resulted to be an effective treatment
      with pleasant aesthetic outcome and no seroma recurrence. Silent seromas should
      be considered as a possible etiologic factor of scar asymmetries appearing during
      late follow-up after abdominoplasty. 

PMID- 23143815
TI  - Environmental allergies and respiratory morbidities in cystic fibrosis.
AB  - BACKGROUND: Cystic fibrosis (CF) is characterized by recurrent respiratory
      infections and progressive lung disease. Although environmental factors account
      for 50% of the variation in CF lung function, few specific exposures have been
      identified. Studies using small study samples focusing on environmental allergies
      in CF have had inconsistent results. Our objective was to examine the role of
      environmental allergies in upper and lower respiratory tract morbidities in CF.
      METHODS: A total of 1,321 subjects with CF were recruited through the U.S. CF
      Twin-Sibling Study. Questionnaires were used to determine the presence/absence of
      environmental allergies. Questionnaires, chart review, and U.S. CF Foundation
      Patient Registry data were used to track outcomes. RESULTS: Within the study
      sample 14% reported environmental allergies. Environmental allergies were
      associated with a higher risk of sinus disease (adjusted OR: 2.68; P < 0.001) and
      nasal polyps (adjusted OR: 1.74; P = 0.003). Environmental allergies were also
      associated with a more rapid decline in lung function (additional -1.1%/year; P =
      0.001). However, allergies were associated with a later median age of acquisition
      of Pseudomonas aeruginosa (6.6 years vs. 4.4 years; log rank P = 0.027). The
      reported use of common allergy medications, anti-histamines and leukotriene
      inhibitors, did not alter the frequency of respiratory morbidities. CONCLUSIONS:
      Environmental allergies are associated with an increased risk of sinus disease
      and nasal polyps and a more rapid decline in CF lung function, but may have a
      protective effect against the acquisition of P. aeruginosa. Prospective studies
      are needed to confirm these associations which have implications for more
      aggressive management of allergies.

PMID- 23143816
TI  - Twenty years of work-related injury and illness among union carpenters in
      Washington State.
AB  - BACKGROUND: Individuals who work in the construction industry are at high risk of
      occupational injury. Robust surveillance systems are needed to monitor the
      experiences of these workers over time. METHODS: We updated important
      surveillance data for a unique occupational cohort of union construction workers
      to provide information on long-term trends in their reported work-related
      injuries and conditions. Combining administrative data sources, we identified a
      dynamic cohort of union carpenters who worked in Washington State from 1989
      through 2008, their hours worked by month, and their workers' compensation
      claims. Incidence rates of reported work-related injuries and illnesses were
      examined. Poisson regression was used to assess risk by categories of age,
      gender, time in the union, and calendar time contrasting medical only and paid
      lost time claims. RESULTS: Over the 20-year study period, 24,830 carpenters
      worked 192.4 million work hours. Work-related injuries resulting in medical care
      or paid lost time (PLT) from work occurred at a rate of 24.3 per 200,000 hr
      worked (95% CI: 23.5-25.0). Medical only claims declined 62% and PLT claims
      declined 77%; more substantive declines were seen for injuries resulting from
      being struck and falls to a lower level than from overexertion with lifting.
      Differences in risk based on union tenure and age diminished over time as well.
      CONCLUSIONS: Significant declines in rates of reported work-related injuries and
      illnesses were observed over the 20-year period among these union carpenters.
      Greater declines were observed among workers with less union tenure and for
      claims resulting in PLT.

PMID- 23143817
TI  - Drug delivery from hydroxyapatite-coated titanium surfaces using biodegradable
      particle carriers.
AB  - The goal of this study was to develop a functional titanium (Ti) implant loaded
      with bioactive molecules using biodegradable polymeric particles as drug delivery
      carrier for dental applications. In this study, dexamethasone (DEX)-loaded
      poly(lactic-co-glycolic acid) (PLGA) particles were electrostatically immobilized
      on a Ti disc surface coated with hydroxyapatite (HA) nanocrystals using a low
      temperature high speed collision (LTHSC) method. Resorbable blasting media (RBM)
      Ti discs (S1), HA-Ti discs (S2), and HA-Ti discs treated with DEX-loaded PLGA
      particles (S3) were fabricated in this study as sample discs. To facilitate
      surface immobilization, PLGA particles were coated with polyethyleneimine (PEI)
      to produce a positive surface charge. This modification of PLGA particle
      surfaces, allowed DEX-loaded PLGA particles to be immobilized on negatively
      charged S2 disc surface. It was found that DEX-loaded PLGA particles were well
      dispersed and immobilized onto the S3 disc surfaces. Release profile studies of
      DEX from S3 discs in a 4-week immersion study indicated an initial burst release
      followed by sustained release. In vitro evaluation of bone marrow derived
      mesenchymal stem cells (BMSCs) cultured for 1 and 2 weeks on S3 discs showed
      greater BMSC differentiation than on S1 or S2 discs, demonstrating that this
      innovative delivery platform potently induced BMSC differentiation in vitro, and
      suggesting that it could be exploited for stem cell therapy purposes or to
      enhance in vivo osteogenesis. In addition, the results of the present study shows
      that various bioactive molecules that promote bone regeneration can be
      efficiently incorporated onto HA-Ti surfaces using biodegradable polymeric
      particles.

PMID- 23143818
TI  - How and when to decide on revascularization in stable ischemic heart disease.
AB  - OPINION STATEMENT: Coronary artery disease is the leading cause of death and
      disability worldwide. While an invasive strategy of early revascularization
      reduces cardiovascular morbidity and mortality in patients with acute coronary
      syndromes, there is no convincing evidence that this strategy leads to an
      incremental survival advantage for patients with stable ischemic heart disease
      (SIHD) beyond that achieved by optimal medical therapy. Two landmark trials,
      COURAGE and BARI 2D, suggest that a strategy of aggressive medical therapy is a
      reasonable initial approach to such patients. However, there remain certain
      groups of patients, those with at least moderate ischemia on baseline stress
      testing, where there is still clinical equipoise. Major society guidelines favor
      revascularization based on observational data and trials of CABG conducted
      decades ago, yet data from modern randomized trials are lacking. Ongoing trials
      such as ISCHEMIA should provide clinicians with evidence to guide selection of
      the appropriate initial management strategy for patients with SIHD.

PMID- 23143819
TI  - Macroscopic nanoparticle ribbons and fabrics.

PMID- 23143820
TI  - The need for an integrated approach to the global challenge of POPs management.

PMID- 23143821
TI  - Effects of chronic exposure to radiofrequency electromagnetic fields on energy
      balance in developing rats.
AB  - The effects of radiofrequency electromagnetic fields (RF-EMF) on the control of
      body energy balance in developing organisms have not been studied, despite the
      involvement of energy status in vital physiological functions. We examined the
      effects of chronic RF-EMF exposure (900 MHz, 1 V m(-1)) on the main functions
      involved in body energy homeostasis (feeding behaviour, sleep and
      thermoregulatory processes). Thirteen juvenile male Wistar rats were exposed to
      continuous RF-EMF for 5 weeks at 24  degrees C of air temperature (T a) and
      compared with 11 non-exposed animals. Hence, at the beginning of the 6th week of
      exposure, the functions were recorded at T a of 24  degrees C and then at 31 
      degrees C. We showed that the frequency of rapid eye movement sleep episodes was
      greater in the RF-EMF-exposed group, independently of T a (+42.1 % at 24  degrees
      C and +31.6 % at 31  degrees C). The other effects of RF-EMF exposure on several
      sleep parameters were dependent on T a. At 31  degrees C, RF-EMF-exposed animals
      had a significantly lower subcutaneous tail temperature (-1.21  degrees C) than
      controls at all sleep stages; this suggested peripheral vasoconstriction, which
      was confirmed in an experiment with the vasodilatator prazosin. Exposure to RF
      EMF also increased daytime food intake (+0.22 g h(-1)). Most of the observed
      effects of RF-EMF exposure were dependent on T a. Exposure to RF-EMF appears to
      modify the functioning of vasomotor tone by acting peripherally through alpha
      adrenoceptors. The elicited vasoconstriction may restrict body cooling, whereas
      energy intake increases. Our results show that RF-EMF exposure can induce energy
      saving processes without strongly disturbing the overall sleep pattern.

PMID- 23143822
TI  - Colloidal diatomite, radionickel, and humic substance interaction: a combined
      batch, XPS, and EXAFS investigation.
AB  - This work determined the influence of humic acid (HA) and fulvic acid (FA) on the
      interaction mechanism and microstructure of Ni(II) onto diatomite by using batch
      experiments, X-ray photoelectron spectroscopy (XPS), and extended X-ray
      absorption fine structure (EXAFS) methods. Macroscopic and spectroscopic
      experiments have been combined to see the evolution of the interaction mechanism
      and microstructure of Ni(II) in the presence of HA/FA as compared with that in
      the absence of HA/FA. The results indicated that the interaction of Ni(II) with
      diatomite presents the expected solution pH edge at 7.0, which is modified by
      addition of HA/FA. In the presence of HA/FA, the interaction of Ni(II) with
      diatomite increased below solution pH 7.0, while Ni(II) interaction decreased
      above solution pH 7.0. XPS analysis suggested that the enrichment of Ni(II) onto
      diatomite may be due to the formation of (=SO)2Ni. EXAFS results showed that
      binary surface complexes and ternary surface complexes of Ni(II) can be
      simultaneously formed in the presence of HA/FA, whereas only binary surface
      complexes of Ni(II) are formed in the absence of HA/FA, which contribute to the
      enhanced Ni(II) uptake at low pH values. The results observed in this work are
      important for the evaluation of Ni(II) and related radionuclide physicochemical
      behavior in the natural soil and water environment.

PMID- 23143823
TI  - Enzymatic biomarkers as indicators of dietary cadmium in gypsy moth caterpillars.
AB  - Heavy metals damage the structure, chemistry, and function of cells, including
      enzyme systems inside them. Variation in the profile of biochemical biomarkers in
      prevalent species should be used for assessing environmental contamination. The
      present study pays attention to the phosphatases present in the midgut of gypsy
      moth fourth instar caterpillars, which had been exposed to short- and long-term
      cadmium intake at 10 and 30 MUg Cd/g dry food. Chronic cadmium ingestion
      significantly inhibited the activity of all examined phosphatases, while only the
      activity of lysosomal phosphatase was acutely decreased. Total acid phosphatase
      activity recovered from both long-term cadmium treatments within 3 days. The low
      index of phenotypic plasticity was connected to high variability of plasticity.
      Dependence of phosphatase isoforms on genotype and duration of cadmium treatment
      was determined. We concluded that, with further investigations, profiling of
      total acid phosphatase activity, as well as the lysosomal fraction can be used as
      a biomarker for acute sublethal metal toxicity.

PMID- 23143824
TI  - Longitudinal variations in indoor VOC concentrations after moving into new
      apartments and indoor source characterization.
AB  - This study examined the indoor concentrations of a wide range of volatile organic
      compounds (VOCs) in currently built new apartments every month over a 24-month
      period and the source characteristics of indoor VOCs. The indoor total VOC (TVOC)
      concentrations exhibited a decreasing tendency over the 24-month follow-up
      period. Similar to TVOCs, the median indoor concentrations of 33 of 40 individual
      VOCs (all except for naphthalene and six halogenated VOCs) revealed decreasing
      tendencies. In contrast, the indoor concentrations of the six halogenated VOCs
      did not reveal any definite trend with time. Moreover, the indoor concentrations
      of those halogenated VOCs were similar to the outdoor concentrations, suggesting
      the absence of any notable indoor sources of halogenated VOCs. For naphthalene
      (NT), the indoor concentrations were significantly higher than the outdoor
      concentrations, suggesting the presence of indoor NT source(s). The floor/wall
      coverings (39 %) were the most influential indoor source of indoor VOCs, followed
      by household cleaning products (32 %), wood paneling/furniture (17 %), paints (7
      %), and moth repellents (5 %).

PMID- 23143825
TI  - Effect of NaCl on ESPT-mediated FRET in a CTAC micelle: a femtosecond and FCS
      study.
AB  - Femtosecond upconversion, single-molecule fluorescence resonance energy transfer
      (sm-FRET) and fluorescence correlation spectroscopy (FCS) are applied to study
      the competition between excited-state proton transfer (ESPT) and FRET [to
      rhodamine 6G (R6G)] of 8-hydroxypyranine-1,3,6-trisulfonate (HPTS) in
      cetyltrimethylammonium chloride (CTAC) micelles. Pyranine exhibits dual emission
      at lambda(em)=430 nm for ROH and 520 nm for RO(-). The absorption spectrum of R6G
      (acceptor) has very good overlap with the RO(-) emission and poor overlap with
      ROH emission. It is observed that FRET occurs readily from the RO(-)* state of
      HPTS (donor) to R6G (acceptor). Multiple timescales of FRET were detected from
      the rise time of acceptor emission. The different timescales correspond to
      different donor-acceptor distances. The ultrafast components (8.5 and 13 ps) are
      assigned to FRET at a close contact of donor and acceptor (~20 A). The longer
      components (500 and 800 ps) arise from long-distance FRET from the donor to the
      acceptor (~40 A) located in different regions of the CTAC micelle. The larger
      donor-acceptor distances agree with those obtained from an sm-FRET study. On
      addition of 4 M NaCl to CTAC, the rate of proton transfer (k(PT)) slowed by about
      eight and two times, respectively, for the fast and slow sites of the CTAC
      micelle. As a result, the intensity of the ROH emission increases and that of RO(
      ) decreases. The decrease in the intensity of the RO(-) emission causes a
      decrease in the efficiency of FRET.

PMID- 23143827
TI  - [Look back and look ahead at 25 answers on "questions from research practice"].

PMID- 23143826
TI  - A docking-based receptor library of antibiotics and its novel application in
      predicting chronic mixture toxicity for environmental risk assessment.
AB  - As organisms are typically exposed to chemical mixtures over long periods of
      time, chronic mixture toxicity is the best way to perform an environmental risk
      assessment (ERA). However, it is difficult to obtain the chronic mixture toxicity
      data due to the high expense and the complexity of the data acquisition method.
      Therefore, an approach was proposed in this study to predict chronic mixture
      toxicity. The acute (15 min exposure) and chronic (24 h exposure) toxicity of
      eight antibiotics and trimethoprim to Vibrio fischeri were determined in both
      single and binary mixtures. The results indicated that the risk quotients (RQs)
      of antibiotics should be based on the chronic mixture toxicity. To predict the
      chronic mixture toxicity, a docking-based receptor library of antibiotics and the
      receptor-library-based quantitative structure-activity relationship (QSAR) model
      were developed. Application of the developed QSAR model to the ERA of antibiotic
      mixtures demonstrated that there was a close affinity between RQs based on the
      observed chronic toxicity and the corresponding RQs based on the predicted data.
      The average coefficients of variations were 46.26 and 34.93 % and the
      determination coefficients (R (2)) were 0.999 and 0.998 for the low concentration
      group and the high concentration group, respectively. This result convinced us
      that the receptor library would be a promising tool for predicting the chronic
      mixture toxicity of antibiotics and that it can be further applied in ERA.

PMID- 23143828
TI  - [The project of the Techniker-Krankenkasse: some comments on the results by the
      project's scientific advisory board].
AB  - The Project of the Techniker Krankenkasse compared 2 systems of quality assurance
      in outpatient psychotherapy, the established peer review system based on
      qualitative individual case reports and a new model based on psychometric
      assessment and feed-back systems. In this publication the members of the project
      advisory board comment on the results and limitations of the study. 400
      psychotherapists in private practice participated in a cluster-randomized
      comparison study, 200 were allocated to the intervention group, and 200 to the
      control group. In both groups assessments were performed at 3 points in time, one
      at the beginning of treatment, one at the end of treatment and one at follow-up
      12 months post-treatment. No significant differences in psychotherapeutic outcome
      were observed in the 2 groups. The hypothesis of a better outcome associated with
      the psychometric assessment and benchmarking procedure was not confirmed.

PMID- 23143829
TI  - [Psychosocial therapies in severe mental illness: DGPPN-S3-guideline: evidence,
      recommendations and challenges for mental health service research].
AB  - Severe mental illness is associated with long-lasting symptoms and various
      impairments including individual, social and occupational aspects. The S3
      guideline on psychosocial therapies in severe mental illness of the Germany
      Society for Psychiatry, Psychotherapy and Neurology (DGPPN) offers
      recommendations for psychosocial interventions. This paper emphasizes specific
      characteristics of the S3 guidelines on psychosocial therapies in severe mental
      illness and summarizes the primary results. Areas of future mental health service
      research are identified.

PMID- 23143830
TI  - [Including or excluding data: intention-to-treat and completer analyses].

PMID- 23143831
TI  - [Clinical diagnostics and evidence-based psychotherapy of patients with obsessive
      compulsive disorders (OCD)].

PMID- 23143832
TI  - Plasma and urine dimercaptopropanesulfonate concentrations after dermal
      application of transdermal DMPS (TD-DMPS).
AB  - 2,3-Dimercaptopropane-1-sulfonate (DMPS) is a metal chelator approved in Europe
      for oral or intravenous use for heavy metal poisoning. Transdermally applied DMPS
      (TD-DMPS) is used by some alternative practitioners to treat autism, despite the
      absence of evidence for its efficacy. We found no literature evaluating the
      pharmacokinetics of the transdermal route of delivery or the ability of TD-DMPS
      to enhance urinary mercury elimination. We hypothesized that TD-DMPS is not
      absorbed. Eight adult volunteers underwent application of 1.5-3 drops/kg of TD
      DMPS. Subjects provided 12-h urine collections the day before and day of
      application. Subjects underwent blood draws at 0, 30, 60,90, 120, and 240 min
      after TD-DMPS application. Plasma and urine were assayed for the presence of
      DMPS. Urine was assayed for any change in urinary mercury excretion after DMPS.
      One control subject ingested 250 mg of oral DMPS and underwent the same urine and
      blood collections and analyses. No subject had detectable urine DMPS or increased
      urine mercury excretion after TD-DMPS. One subject had detectable levels of DMPS
      in the 30-min plasma sample, suspected to be contamination. All other samples for
      that subject and the other seven subjects showed no detectable plasma DMPS. The
      control subject had detectable urine and plasma DMPS levels and increased urine
      mercury excretion. These results indicate that TD-DMPS is not absorbed. There was
      no increase in urine mercury excretion after TD-DMPS. Our results argue that TD
      DMPS is an ineffective metal chelator.

PMID- 23143833
TI  - Festival food coma in cystic fibrosis.
AB  - Children with cystic fibrosis liver disease and portal hypertension are at risk
      of developing acute hepatic encephalopathy. Even in the presence of normal
      synthetic liver function these children may have porto-systemic shunting. We
      report a case of an adolosecent who had cystic fibrosis liver disease and
      presented with life threatening hepatinc encephalopathy. This case illustrates
      that it is necessary to consider an appropriate dietary regimen in adolosecents
      with liver disease to prevent hepatic decompensation.

PMID- 23143834
TI  - Occupational exposure and mortality among workers at three titanium dioxide
      plants.
AB  - BACKGROUND: A cohort of 3,607 workers employed in three DuPont titanium dioxide
      production facilities was followed from 1935 through 2006. METHODS: Combined and
      plant-specific cohort mortality was compared with the overall US population and
      other DuPont employees. The relationships between selected causes of death and
      annual cumulative exposures to titanium dioxide and chloride were investigated
      using Poisson regression methods to examine trends with increasing exposure.
      RESULTS: Among the 833 deaths, no causes of deaths were statistically
      significantly elevated either overall or plant-specific when compared to the US
      population. Compared to DuPont workers, statistically significantly elevated SMRs
      for all causes, all cancers, and lung cancers were found driven by the workers at
      the oldest plant. Comparing increasing exposure groups to the lowest group,
      disease risk did not increase with exposure. CONCLUSIONS: There was no indication
      of a positive association between occupational exposure and death from all
      causes, all cancers, lung cancers, non-malignant respiratory disease, or all
      heart disease.

PMID- 23143835
TI  - The relationship between intracellular and plasma levels of folate and
      metabolites in the methionine cycle: a model.
AB  - SCOPE: Folate status and the status of the methionine cycle are typically
      assessed by measuring folate and metabolites in the plasma. It is assumed that
      plasma metabolite levels are proportional to their levels in tissues, but there
      is little information to support this assumption. METHODS AND RESULTS: We
      developed a mathematical model, based on known kinetics of the methionine cycle
      in the liver and tissues, and the transport kinetics of metabolites into and out
      of the plasma. We use the model to explore the relationship between folate status
      and metabolite values in the plasma, the relationships between metabolite values
      and methylation capacity, the response to a methionine load, and the half-life of
      folate in plasma and tissues. We also use the model to study the effects of Down
      syndrome and oxidative stress on metabolite values in plasma and tissues. The
      model accurately reproduces measured metabolite values pre- and post-folate
      fortification. The model shows that a high acute intake of folate remains largely
      restricted to the plasma and is rapidly excreted; only a prolonged exposure to
      increased folate elevates tissue folate significantly. CONCLUSION: The model
      accurately reproduces experimental and clinical findings and can serve as a
      platform to study, in silico, the relationships between metabolite values in
      tissues and plasma, and how these vary with methionine and B vitamin input, and
      with mutations in the genes for enzymes in the methionine cycle.

PMID- 23143836
TI  - Direct copper-catalyzed alpha-arylation of benzyl phenyl ketones with aryl
      iodides: route towards tamoxifen.

PMID- 23143837
TI  - Isolation and structural elucidation of armeniaspirols A-C: potent antibiotics
      against gram-positive pathogens.
AB  - In an antibiotic lead discovery program, the known strain Streptomyces armeniacus
      DSM19369 has been found to produce three new natural products when cultivated on
      a malt-containing medium. The challenging structural elucidation of the isolated
      compounds was achieved by using three independent methods, that is, chemical
      degradation followed by NMR spectroscopy, a computer-assisted structure
      prediction algorithm, and X-ray crystallography. The compounds, named
      armeniaspirol A-C (2-4), exhibit a compact, hitherto unprecedented chlorinated
      spiro[4.4]non-8-ene scaffold. Labeling experiments with [1-(13)C] acetate, [1,2
      (13)C2] acetate, and [U-(13)C] proline suggest a biosynthesis through a rare two
      chain mechanism. Armeniaspirols displayed moderate to high in vitro activities
      against gram-positive pathogens such as methicillin-resistant S. aureus (MRSA) or
      vancomycin resistant E. faecium (VRE). As analogue 2 was active in vivo in an
      MRSA sepsis model, and showed no development of resistance in a serial passaging
      experiment, it represents a new antibiotic lead structure.

PMID- 23143838
TI  - Case-based ethics instruction: the influence of contextual and individual factors
      in case content on ethical decision-making.
AB  - Cases have been employed across multiple disciplines, including ethics education,
      as effective pedagogical tools. However, the benefit of case-based learning in
      the ethics domain varies across cases, suggesting that not all cases are equal in
      terms of pedagogical value. Indeed, case content appears to influence the extent
      to which cases promote learning and transfer. Consistent with this argument, the
      current study explored the influences of contextual and personal factors embedded
      in case content on ethical decision-making. Cases were manipulated to include a
      clear description of the social context and the goals of the characters involved.
      Results indicated that social context, specifically the description of an
      autonomy-supportive environment, facilitated execution of sense making processes
      and resulted in greater decision ethicality. Implications for designing optimal
      cases and case-based training programs are discussed.

PMID- 23143839
TI  - Magnetic resonance (MR) imaging and MR cholangiopancreatography findings in cats
      with cholangitis and pancreatitis.
AB  - Cholangiohepatitis/cholangitis is second only to hepatic lipidosis as the most
      common liver disease in cats and is often associated with concurrent
      pancreatitis. Magnetic resonance imaging (MRI) and MR cholangiopancreatography
      (MRCP) have developed into an accurate, highly sensitive and specific imaging
      tool for the diagnosis of biliary and pancreatic duct disorders in humans. In
      this prospective case series, 10 cats with suspected cholangitis and/or
      pancreatitis were enrolled based on clinical history, physical examination and
      appropriate diagnostic test results. MRI and MRCP sequences with secretin
      stimulation of the cranial abdomen were performed, and sonography and
      laparoscopic biopsies for histologic diagnosis were obtained for comparison. MRI
      detected pancreatic abnormalities in cats suspected of pancreatitis, including T1
      pre-contrast hypointense and T2 hyperintense pancreatic parenchyma and a dilated
      pancreatic duct. The MRI findings of the liver were non-specific. Nine of 10 cats
      had biliary abnormalities, including gall bladder wall thickening, gall bladder
      wall moderate contrast enhancement and/or gall bladder debris. Eight of 10 cats
      had histologic evidence of pancreatitis, as well as hepatitis or cholangitis,
      with one cat diagnosed with hepatic lymphoma. The advantages of MRI/MRCP over
      sonography of these cats included the striking pancreatic signal changes
      associated with pancreatitis and the ability to comprehensibly assess and measure
      the pancreas and hepatobiliary structures without operator dependence or
      interference from bowel gas. MRI/MRCP imaging of the feline abdomen may be
      beneficial in cases with equivocal ultrasound imaging findings.

PMID- 23143840
TI  - Three clinical cases of Anaplasma phagocytophilum infection in cats in Poland.
AB  - The purpose of this study was to describe Anaplasma phagocytophilum infection of
      three cats in Poland showing signs of fever, swollen and painful joints, pale
      mucous membranes and epistaxis. Morulae consistent with A phagocytophilum were
      present within the neutrophils of two of the cats. A polymerase chain reaction
      (PCR) was found targeting the 16S rRNA gene amplified DNA consistent with A
      phagocytophilum in the blood of all three cats. The sequence of the PCR product
      obtained showed 99.6-100% homology with the sequence of A phagocytophilum, gene
      number EU 090186 from Genbank. Applied therapy (including administration of
      tetracyclines for 3 weeks) resulted in a gradual clinical recovery.

PMID- 23143841
TI  - Surgical resection of lung cancer in England: more operations but no trials to
      test their effectiveness.

PMID- 23143842
TI  - Treating idiopathic pulmonary fibrosis with the addition of co-trimoxazole: a
      randomised controlled trial.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal condition with limited
      treatment options. However, in a previous small study, co-trimoxazole was found
      to be beneficial. METHODS: In a double-blind multicentre study, 181 patients with
      fibrotic idiopathic interstitial pneumonia (89% diagnosed as definite/probable
      IPF) were randomised to receive co-trimoxazole 960 mg twice daily or placebo for
      12 months in addition to usual care. Measurements were made of forced vital
      capacity (FVC) (primary endpoint), diffusing capacity of carbon monoxide (Dlco)
      and EuroQol (EQ5D)-based utility, 6-minute walk test (6MWT) and Medical Research
      Council (MRC) dyspnoea score (secondary endpoints). All-cause mortality and
      adverse events were recorded (tertiary endpoints). RESULTS: Co-trimoxazole had no
      effect on FVC (mean difference 15.5 ml (95% CI -93.6 to 124.6)), Dlco (mean
      difference -0.12 mmol/min/kPa (95% CI 0.41 to 0.17)), 6MWT or MRC dyspnoea score
      (intention-to-treat analysis). The findings of the per-protocol analysis were the
      same except that co-trimoxazole treatment resulted in a significant improvement
      in EQ5D-based utility (mean difference 0.12 (95% CI 0.01 to 0.22)), a reduction
      in the percentage of patients requiring an increase in oxygen therapy (OR 0.05
      (95% CI 0.00 to 0.61)) and a significant reduction in all-cause mortality (co
      trimoxazole 3/53, placebo 14/65, HR 0.21 (95% CI 0.06 to 0.78), p=0.02)) compared
      with placebo. The use of co-trimoxazole reduced respiratory tract infections but
      increased the incidence of nausea and rash. CONCLUSIONS: The addition of co
      trimoxazole therapy to standard treatment for fibrotic idiopathic interstitial
      pneumonia had no effect on lung function but resulted in improved quality of life
      and a reduction in mortality in those adhering to treatment. ISRCTN22201583.

PMID- 23143843
TI  - Molecular mechanisms underlying behaviors related to nicotine addiction.
AB  - Tobacco smoking results in more than 5 million deaths each year and accounts for
      almost 90% of all deaths from lung cancer. Nicotine, the major reinforcing
      component of tobacco smoke, acts in the brain through the neuronal nicotinic
      acetylcholine receptors (nAChRs). The nAChRs are allosterically regulated, ligand
      gated ion channels consisting of five membrane-spanning subunits. Twelve
      mammalian alpha subunits (alpha2-alpha10) and beta subunits (beta2-beta4) have
      been cloned. The predominant nAChR subtypes in mammalian brain are those
      containing alpha4 and beta2 subunits (denoted as alpha4beta2* nAChRs). The
      alpha4beta2* nAChRs mediate many behaviors related to nicotine addiction and are
      the primary targets for currently approved smoking cessation agents. Considering
      the large number of nAChR subunits in the brain, it is likely that nAChRs
      containing subunits in addition to alpha4 and beta2 also play a role in tobacco
      smoking. Indeed, genetic variation in the CHRNA5-CHRNA3-CHRNB4 gene cluster,
      encoding the alpha5, alpha3, and beta4 nAChR subunits, respectively, has been
      shown to increase vulnerability to tobacco dependence and smoking-associated
      diseases including lung cancer. Moreover, mice in which expression of alpha5 or
      beta4 subunits has been genetically modified have profoundly altered patterns of
      nicotine consumption. In addition to the reinforcing properties of nicotine, the
      effects of nicotine on appetite, attention, and mood are also thought to
      contribute to establishment and maintenance of the tobacco smoking habit. Here we
      review recent insights into the behavioral actions of nicotine and the nAChRs
      subtypes involved, which likely contribute to the development of tobacco
      dependence in smokers.

PMID- 23143845
TI  - Solution-processed small molecules as mixed host for highly efficient blue and
      white phosphorescent organic light-emitting diodes.
AB  - The widely used hole-transporting host 4,4',4"-tris(N-carbazolyl)-triphenylamine
      (TCTA) blended with either a hole-transporting or an electron-transporting small
      molecule material as a mixed-host was investigated in the phosphorescent organic
      light-emitting diodes (OLEDs) fabricated by the low-cost solution-process. The
      performance of the solution-processed OLEDs was found to be very sensitive to the
      composition of the mixed-host systems. The incorporation of the hole-transporting
      1,1-bis[(di-4-tolylamino)phenyl]cyclohexane (TAPC) into TCTA as the mixed-host
      was demonstrated to greatly reduce the driving voltage and thus enhance the
      efficiency due to the improvement of hole injection and transport. On the basis
      of the mixed-host of TCTA:TAPC, we successfully fabricated low driving voltage
      and high efficiency blue and white phosphorescent OLEDs. A maximum forward
      viewing current efficiency of 32.0 cd/A and power efficiency of 25.9 lm/W were
      obtained in the optimized mixed-host blue OLED, which remained at 29.6 cd/A and
      19.1 lm/W at the luminance of 1000 cd/m(2) with a driving voltage as low as 4.9
      V. The maximum efficiencies of 37.1 cd/A and 32.1 lm/W were achieved in a single
      emissive layer white OLED based on the TCTA:TAPC mixed-host. Even at 1000
      cd/m(2), the efficiencies still reach 34.2 cd/A and 23.3 lm/W and the driving
      voltage is only 4.6 V, which is comparable to those reported from the state-of
      the-art vacuum-evaporation deposited white OLEDs.

PMID- 23143846
TI  - Testing messages to encourage discussion of clinical trials among cancer
      survivors and their physicians: examining monitoring style and message detail.
AB  - Encouraging cancer survivors to discuss clinical trials with their physicians may
      increase enrollment in clinical trials. Health messages offer one method for
      encouraging such discussions. We hypothesized that matching messages to an
      individual's preference for detailed or non-detailed information (i.e.,
      monitoring style) would result in more discussions. Participants (N = 538) were
      cancer survivors, who phoned the National Cancer Institute's Cancer Information
      Service (CIS). Participants were classified as higher or lower monitors and then
      randomized to receive detailed or non-detailed messages in the mail 1 and 4 weeks
      following their baseline CIS call. At 12 weeks, there was a significant
      interaction between monitoring style and message detail. Follow-up analyses were
      nonsignificant but suggested a theoretically consistent pattern in which non
      detailed messages were more effective among lower monitors. These findings imply
      that providing extremely detailed information may be excessive, even to
      individuals engaged in information seeking behavior.

PMID- 23143844
TI  - HIV-1 pathogenesis: the virus.
AB  - Transmission of HIV-1 results in the establishment of a new infection, typically
      starting from a single virus particle. That virion replicates to generate viremia
      and persistent infection in all of the lymphoid tissue in the body. HIV-1
      preferentially infects T cells with high levels of CD4 and those subsets of T
      cells that express CCR5, particularly memory T cells. Most of the replicating
      virus is in the lymphoid tissue, yet most of samples studied are from blood. For
      the most part the tissue and blood viruses represent a well-mixed population.
      With the onset of immunodeficiency, the virus evolves to infect new cell types.
      The tropism switch involves switching from using CCR5 to CXCR4 and corresponds to
      an expansion of infected cells to include naive CD4(+) T cells. Similarly, the
      virus evolves the ability to enter cells with low levels of CD4 on the surface
      and this potentiates the ability to infect macrophages, although the scope of
      sites where infection of macrophages occurs and the link to pathogenesis is only
      partly known and is clear only for infection of the central nervous system. A
      model linking viral evolution to these two pathways has been proposed. Finally,
      other disease states related to immunodeficiency may be the result of viral
      infection of additional tissues, although the evidence for a direct role for the
      virus is less strong. Advancing immunodeficiency creates an environment in which
      viral evolution results in viral variants that can target new cell types to
      generate yet another class of opportunistic infections (i.e., HIV-1 with altered
      tropism).

PMID- 23143848
TI  - Papers presented at the annual meetings of the Knee Society: editorial comment.

PMID- 23143847
TI  - ortho-Phenylenediamine: an effective spacer to build highly magnetic Fe3O4/Au
      nanocomposites.
AB  - 1,2-Diaminobenzene, popularly known as ortho-phenylenediamine (PDA), is found to
      be a prototype spacer for the deposition of gold nanoparticles on the surfaces of
      Fe(3)O(4) microspheres. Upon carbonization with PDA, the morphology of the
      product changes significantly, and the resulting nanocomposites exhibit enhanced
      magnetism beyond the saturation value of Fe(3)O(4). The Fe(3)O(4)/Au
      nanocomposites show good surface-enhanced Raman spectroscopy activity with a
      detection limit of 10(-15)  M.

PMID- 23143850
TI  - A comparison of the solid-state structures of halogen azides XN3 (X=Cl, Br, I).

PMID- 23143851
TI  - Comparison of opioid-related deaths by work-related injury.
AB  - OBJECTIVE: To infer whether work-related injuries may impact opioid-related
      deaths. METHODS: Descriptive comparisons were done using data from the Utah
      Department of Health, the Office of Medical Examiners, and the Labor Commission
      on all Utah residents who died from opioid-related deaths from 2008 to 2009.
      RESULTS: The majority of decedents (145 of 254, 57%) had at least one prior work
      related injury. Demographics were similar regardless of work injury status.
      However, lack of high school diploma (18% vs. 7%, P < 0.001), prevalence of
      mental illness (50% vs. 15%, P < 0.001), tobacco (61% vs. 12%, P < 0.001),
      alcohol (87% vs. 28%, P < 0.001), and illicit drug (50% vs. 4%, P < 0.001) use
      were all substantially higher than the background population. CONCLUSION: A
      detailed history and screening for mental illness and substance abuse, including
      tobacco use, among injured workers may be helpful in avoiding potential opioid
      related deaths.

PMID- 23143849
TI  - Obesity in children with poorly controlled asthma: Sex differences.
AB  - BACKGROUND: Obesity increases asthma risk, and may alter asthma severity. In
      adults, sex appears to modify the effect of obesity on asthma. Among children,
      the effect of sex on the relationship between obesity and asthma severity remains
      less clear, particularly when considering race. OBJECTIVE: To determine how
      obesity affects disease characteristics in a diverse cohort of children with
      poorly controlled asthma, and if obesity effects are altered by sex. DESIGN: We
      analyzed 306 children between 6 and 17 years of age with poorly controlled asthma
      enrolled in a 6-month trial assessing lansoprazole for asthma control. In this
      secondary analysis, we determined associations between obesity and symptom
      severity, spirometry, exacerbation risk, airway biomarkers, bronchial reactivity,
      and airflow perception. We used both a multivariate linear regression and
      longitudinal mixed-effect model to determine if obesity interacted with sex to
      affect asthma severity. RESULTS: Regardless of sex, BMI >95th percentile did not
      affect asthma control, exacerbation risk or airway biomarkers. Sex changed the
      effect of obesity on lung function (sex * obesity FEV1%, interaction P-value <
      0.01, sex * obesity FEV1/FVC, interaction P-value = 0.03). Obese males had
      significantly worse airflow obstruction compared to non-obese males, while in
      females there was no obesity effect on airflow obstruction. In females, obesity
      was associated with significantly greater FEV1 and FVC, and a trend toward
      reduced airway reactivity. CONCLUSIONS: Obesity did not affect asthma control,
      airway markers or disease stability; however obesity did affect lung function in
      a sex-dependent manner. In males, obesity associated with reduced FEV1/FVC, and
      in females, obesity associated with substantially improved lung function.

PMID- 23143852
TI  - High-sensitivity real-time analysis of nanoparticle toxicity in green fluorescent
      protein-expressing zebrafish.
AB  - Gold nanoparticles (AuNP) show great potential for diagnostic and therapeutic
      application in humans. A great number of studies have tested the cytotoxicity of
      AuNP using cell culture. There is, however, an urgent need to test AuNP in
      vertebrate animal models that interrogate biodistribution and complex biological
      traits like organ development, whole body metabolism, and cognitive function. The
      sheer number of different compounds precludes the use of small rodent model for
      initial screening. The extended fish embryo test (FET) is used here to bridge the
      gap between cell culture and small animal models. A study on the toxicity of
      ultrasmall AuNP in wild type and transgenic zebrafish is presented. FET
      faithfully reproduce all important findings of a previous study in HeLa cells and
      add new important information on teratogenicity and hepatotoxicity that could not
      be gained from studying cultured cells.

PMID- 23143853
TI  - Diagnostics and treatment of pseudoaneurysms of the distal anterior tibial artery
      after upper ankle joint arthroscopy: a case report and a review of literature.

PMID- 23143854
TI  - tert-Butyldimethylsilyl-directed highly enantioselective approach to axially
      chiral alpha-allenols.
AB  - A highly efficient and enantioselective synthesis of axially chiral alpha
      allenols was realized in practical yields with 96-99% ee or de from TBS-protected
      propargylic alcohols, aldehydes, and a commercially available, inexpensive,
      chiral, secondary amine (S)-alpha,alpha-diphenylprolinol or its enantiomer
      followed by desilylation. The easily removable TBS group not only acts as a
      protecting group, but also as a possible sterically directing group for the
      excellent enantioselectivity and in situ prevention of possible allene
      racemization.

PMID- 23143855
TI  - Consonant development in pediatric cochlear implant users who were implanted
      before 30 months of age.
AB  - This study provided a yearly record of consonant development for the initial 4
      years of cochlear implant (CI) use and established a precedent for using a
      standardized articulation test, the Goldman-Fristoe Test of Articulation-2
      (Goldman, R., & Fristoe, M. [2000]. Goldman-Fristoe Test of Articulation-2.
      Circle Pines, MN: American Guidance Services). The study used CI age as a
      referent for 32 children who received their CI before 30 months of age.
      Consonants produced by 70% of the children were listed, as were the most common
      error types, which were consonant omissions and substitutions. Using consonant
      repertoire lists and standard scores, the study revealed that children with CIs
      had acquisition patterns that were similar to their peers when the duration of CI
      experience was similar to the chronological age norms of typically developing
      children. The results revealed that CI users need time to coordinate their
      articulatory organizing principles with the input they receive from their CI. It
      is appropriate to use length of CI use as a proxy for chronological age during
      the first 4 years when comparing articulation development with hearing peers.

PMID- 23143856
TI  - Comparative interface metrics for metal-free monolayer-based dye-sensitized solar
      cells.
AB  - The first quantitative comparison between self-assembled monolayers of homologous
      carboxylate- and phosphonate-terminated organic dyes that are of use in dye
      sensitized solar cells (DSSCs) is reported. (Cyanovinyl)phosphonate-terminated
      oligothiophenes and (cyanovinyl)carboxylate-terminated oligothiophenes were
      synthesized on TiO(2) thin film electrodes. Structurally analogous organics were
      compared for the effect of the anchoring groups on photochemical properties in
      solution as measured by UV/vis spectroscopy and for reactivity with the electrode
      surface. Monolayers were grown on the TiO(2) electrodes either by "tethering by
      aggregation and growth" (T-BAG) or by solution dipping. Surface roughness and
      homogeneity, elemental composition, and thickness of the monolayers were
      evaluated by atomic force microscopy (AFM), X-ray photoelectron spectroscopy
      (XPS), and ellipsometry. Molecular loadings for each monolayer on TiO(2) were
      quantified by quartz crystal microgravimetry (QCM), and the stability of bonding
      between each class of dyes and the TiO(2) was evaluated by measuring desorption,
      also by QCM; the carboxylates underwent significant dissociation in aqueous media
      but the phosphonates did not. DSSCs were prepared from each congener and from
      simple oligothiophene phosphonates to determine the effect of the cyanovinyl
      group on device behavior; all DSSCs were studied under irradiation from a AM 1.5G
      solar light source; the effect of cyanovinyl group termination was comparable to
      that of adding a thiophene moiety, and the DSSC using a self-assembled monolayer
      of (sexithiophene)phosphonate (6TP) had total power conversion efficiency (eta)
      of ca. 5%.

PMID- 23143857
TI  - Workload and usefulness of daily, centralized home monitoring for patients
      treated with CIEDs: results of the MoniC (Model Project Monitor Centre)
      prospective multicentre study.
AB  - AIM: Automated, daily Home Monitoring (HM) of pacemaker and implantable
      cardioverter-defibrillator (ICD) patients can improve patient care. Yet, HM
      introduction to routine clinical practice is challenged by resource allocation
      for regular HM data review. We tested the feasibility, safety, workload, and
      clinical usefulness of a centralized HM model consisting of one monitor centre
      and nine satellite clinics. METHODS AND RESULTS: Having no knowledge about
      patients' clinical data, a telemonitoring nurse (TN) and a supporting physician
      at the monitor centre screened and filtered HM data in 62 pacemaker and 59 ICD
      patients from nine satellite clinics for over 1 year. Basic screening of
      arrhythmic and technical events required 25.7 min (TN) and 0.7 min (physician)
      per working day, normalized for 100 patients monitored. Communication of relevant
      events to satellite clinics per email or phone required additional 4.3 min (TN)
      and 0.4 min (physician). Telemonitoring nurse also screened for abnormal
      developments in longitudinal data trends weekly for 3 months after implantation,
      and then monthly; one patient session lasted 4.0 +/- 2.9 min. To handle
      transmission-gap notifications, TN needed additional 2.8 min daily. Satellite
      clinics received 231.3 observations from the monitor centre per 100
      patients/year, which prompted 86.3 patient contacts or intensive HM screening
      periods by the satellite clinic itself (37.3% response rate), 51.7 extra follow
      up controls (22.3%), and 30.1 clinical interventions (13.0%). CONCLUSION:
      Centralized HM was feasible, reliable, safe, and clinically useful. Basic
      screening and communication of relevant arrhythmic and technical events required
      a total of 30 min (TN) and 1.1 min (physician) daily per 100 patients monitored.

PMID- 23143858
TI  - Ventricular pacing threshold after transthoracic external defibrillation with two
      different waveforms: an experimental study.
AB  - AIMS: Although an increase in the ventricular pacing threshold (VPT) has been
      observed after administration of transthoracic shock for ventricular
      defibrillation, few studies have evaluated the phenomenon with respect to the
      defibrillation waveform energy. Therefore, this study examined the VPT behaviour
      after transthoracic shock with a monophasic or biphasic energy waveform. METHOD
      AND RESULTS: Domestic Landrace male piglets implanted with a permanent pacemaker
      stimulation system were divided into three groups: no ventricular fibrillation
      (VF) induction and transthoracic shock with monophasic or biphasic energy (group
      I); VF induction, 1 min of observation without intervention, 2 min of external
      cardiac massage, and transthoracic shock with monophasic or biphasic energy
      (group II); and VF induction, 2 min of observation without intervention, 4 min of
      external cardiac massage, and transthoracic shock with monophasic or biphasic
      energy (group III). After external shock, the VPT was evaluated every minute for
      10 min. A total of 143 experiments were performed. At the end of the observation
      period, groups I and II showed steady VPT values. Group III showed an increase in
      VPT with monophasic or biphasic external energy, with no difference between the
      external energy sources. The monophasic but not the biphasic waveform was
      associated with higher VPT values when the VF was longer. CONCLUSION:
      Defibrillation does not have a significant impact on pacing threshold, but a
      longer VF period is related to a higher VPT after defibrillation with monophasic
      waveform.

PMID- 23143859
TI  - Resynchronization improves heart-arterial coupling reducing arterial load
      determinants.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) has benefits on left
      ventricle (LV) performance, but its mid-term effects on LV load and LV-arterial
      coupling are unknown. AIMS: To evaluate CRT mid-term effects on LV-arterial
      coupling, arterial load and its determinants, and the association between CRT
      dependent aortic haemodynamic changes and the arterial biomechanics. METHODS AND
      RESULTS: Cardiac and aortic echographies were done in 25 patients (age: 61 +/- 12
      years; 14 men; New York Heart Association functional classes III-IV; LV ejection
      fraction = 28 +/- 7%, QRS = 139 +/- 20 ms) before and after (23 +/- 12 days) CRT.
      Standard structural and functional parameters and dyssynchrony indices were
      evaluated. Ascending aorta flow and diameter waveforms were measured. Central
      pressure was derived using a transfer function and the diameter calibration
      method. Calculus: arterial elastance (EA); aortic impedance (Zc) and
      distensibility (AD); systemic resistances (SVR), total compliance (CT); global
      reflection coefficient; LV end-systolic elastance (EES); and LV-arterial coupling
      (EA/EES). After CRT EA diminished (-30%;P = 0.001), EES increased (29%; P =
      0.001) and EA/EES improved (pre-CRT: 2.9 +/- 0.9, post-CRT: 1.6 +/- 0.7; P =
      0.001). Arterial elastance changes were associated with changes in arterial
      properties. Cardiac resynchronization therapy was associated with pressure
      independent increase in mean aortic diameter (pre-CRT: 30.0 +/- 4.0 mm, post-CRT:
      33.0 +/- 5.1 mm; P = 0.005) and distensibility (pre-CRT: 3.8 +/- 2.6 * 10(
      3)mmHg(-1), post-CRT: 6.4 +/- 2.5 * 10(-3) mmHg(-1); P = 0.002), and Zc reduction
      (pre-CRT: 3.5 +/- 1.8 * 10(-2)mmHg.s/mL, post-CRT:1.9 +/- 0.8 * 10(-2) mmHg.s/mL;
      P = 0.001) and SVR (pre-CRT:1.7 +/- 0.4 mmHg.s/mL, post-CRT:1.0 +/- 0.3
      mmHg.s/mL; P = 0.001). Changes in EA determinants were associated with changes in
      aortic flow. CONCLUSION: Early after CRT central and peripheral arterial
      biomechanics improved, determining a pressure-independent increase in aortic
      diameter and a reduction in arterial load. Left ventricular systolic performance
      and LV-arterial coupling were enhanced. Arterial biomechanical changes were
      associated with aortic flow changes.

PMID- 23143860
TI  - The relationship between left ventricular scar and ventricular repolarization in
      patients with coronary artery disease: insights from late gadolinium enhancement
      magnetic resonance imaging.
AB  - AIMS: The markers of ventricular repolarization corrected QT interval (QTc), QT
      dispersion (QTD) and Tpeak-to-Tend interval (Tpeak-end) have shown an association
      with sudden cardiac death (SCD) in the general population. However, their
      mechanistic relationship with SCD is unclear. The study aim was to evaluate the
      relationship between QTc, QTD, and Tpeak-end, and the extent and distribution of
      left ventricular (LV) scar in patients with coronary artery disease at high SCD
      risk. METHODS AND RESULTS: We included 64 consecutive implantable cardioverter
      defibrillator (ICD) recipients (66 +/- 11 years, 80% male, median left
      ventricular ejection fraction 30%) who had undergone late gadolinium enhancement
      cardiac magnetic resonance (CMR) imaging prior to device implantation over 4
      years. Scar was quantified using the CMR images and characterized in terms of
      percent LV scar and number of LV segments with subendocardial/transmural scar.
      Repolarization parameters were measured on an electrocardiogram performed prior
      to ICD implantation. After adjustment for potential confounders there was a
      strong association between the number of limited subendocardial (1-25%
      transmurality) scar segments and QTc (P = 0.003), QTD (P = 0.002), and Tpeak-end
      (P = 0.008). However, there was no association between the repolarization
      parameters and percent LV scar or the amount of transmural scar. During a mean
      follow-up of 19 +/- 10 months 19 (30%) patients received appropriate ICD therapy,
      but none of the repolarization parameters were associated with its occurrence.
      CONCLUSION: In this pilot study there was a strong association between limited
      subendocardial LV scar and prolonged QTc, QTD, and Tpeak-end. However, there was
      no association between any of these repolarization markers and the delivery of
      appropriate ICD therapy.

PMID- 23143861
TI  - Use of extracellular matrix materials in patients with endocarditis.
AB  - Tissue replacement is sometimes necessary during surgery for endocarditis.
      Commonly used materials are Dacron, expanded polytetrafluoroethlyene, or bovine
      pericardium. Those materials have no potential for bioresorption and cannot
      restore regional functionality. Extracellular matrices became available lately as
      patch material. Here we present two cases of patients with endocarditis.
      CorMatrix ECM (CorMatrix Cardiovascular, Inc., Atlanta, Georgia, United States)
      was used to repair intracardiac structures with good results in follow-up up to 3
      months. CorMatrix ECM may be an adequate alternative to foreign material for
      patients with endocarditis. 

PMID- 23143862
TI  - A rare pattern of acute type A aortic dissection: circumferential intimal
      invagination.
AB  - A 59-year-old patient with chest pain was transferred to our emergency unit.
      Computed tomography depicted a dissection membrane limited to the aortic root and
      a seemingly normal ascending aorta. Further downstream stenosis of the descending
      aorta appeared. Intraoperatively, complete intimal absence in the ascending aorta
      with intussusception into the descending aorta was evident. Ascending aortic and
      hemiarch replacement was performed. This rare case should raise the surgeons'
      awareness that preoperative imaging can differ considerably from intraoperative
      findings.

PMID- 23143863
TI  - Effect of the phytotherapeutic agent eviprostat on the bladder in a rat model of
      bladder overdistension/emptying.
AB  - AIMS: Ischemia-reperfusion injury is an important factor in the development of
      lower urinary tract symptoms (LUTS) that is partly mediated by the generation of
      free radicals. We investigate the effect of the phytotherapeutic agent
      Eviprostat, a treatment for benign prostatic hyperplasia (BPH) that has
      antioxidant and anti-inflammatory activity, on urinary bladder blood flow (BBF),
      and function in a rat model of bladder overdistension and emptying (OE). METHODS:
      For 8 days before surgery, OE rats received daily oral Eviprostat (36 mg/kg/day)
      or vehicle, while sham-operated animals received vehicle. The bladder was
      distended by infusion of saline over a period of 2 hr (overdistension) and then
      emptied. After 24 hr, BBF was measured with a laser speckle blood flow imager.
      The oxidative-stress marker malondialdehyde (MDA), proinflammatory cytokines, and
      myeloperoxidase were determined in the isolated bladder, and histological
      analysis was performed. Functional contractile responses of bladder strips to
      electrical field stimulation, carbachol, and KCl were measured. RESULTS: Twenty
      four hours after bladder OE, a significant decrease in BBF and significant
      increases in bladder weight, malondialdehyde, proinflammatory cytokines, and
      myeloperoxidase were observed. Eviprostat almost completely prevented these
      changes. Histological analysis of the bladder of OE rats showed hemorrhage,
      accumulation of leukocytes, desquamation of epithelium, and edema, and Eviprostat
      suppressed these changes. The reduction in functional contractile forces in the
      bladder of OE rats was also prevented by Eviprostat. CONCLUSION: Eviprostat
      mediated suppression of increased bladder oxidative stress and inflammation
      caused by bladder OE may contribute to the improvement of BBF and bladder
      function by Eviprostat.

PMID- 23143864
TI  - Respiratory muscle function in patients with cystic fibrosis.
AB  - Respiratory muscle function in patients with cystic fibrosis (CF) can be assessed
      by measurement of maximal inspiratory pressure (Pimax ), maximal expiratory
      pressure (Pemax ), and pressure-time index of the respiratory muscles (PTImus ).
      We investigated the differences in maximal respiratory pressures and PTImus
      between CF patients with no gross hyperinflation and healthy controls and
      described the effects of pulmonary function and nutrition impairment on
      respiratory muscle function in this group of CF patients. Forced expiratory
      volume in 1 sec (FEV1 ), forced vital capacity (FVC) and maximal expiratory flow
      between 25% and 75% of VC (MEF25-75 ), body mass index (BMI), upper arm muscle
      area (UAMA), Pimax , Pemax , and PTImus were assessed in 140 CF patients and in a
      control group of 140 healthy subjects matched for age and gender. Median Pimax
      and Pemax were significantly lower in CF patients compared to the controls [Pimax
      = 74 (57-94) in CF vs. 84 (66-102) in controls, P = 0.009], [Pemax  = 71 (50-95)
      in CF vs. 84 (66-102) in controls, P < 0.001]. Median PTImus in CF patients
      compared to controls was significantly increased [PTImus  = 0.110 (0.076-0.160)
      in CF vs. 0.094 (0.070-0.137) in controls, P = 0.049] and it was significantly
      higher in CF patients with impaired pulmonary function. In CF patients, PTImus
      was significantly negatively related to upper arm muscle area (r = 0.184, P =
      0.031). These findings suggest that CF patients with no severe lung disease
      compared to healthy subjects exhibit impaired respiratory muscle function, while
      CF patients with impaired pulmonary function and nutrition indices exhibit higher
      PTImus values.

PMID- 23143865
TI  - Highly selective 1,4- and 1,6-addition of P(O)-H compounds to p-quinones: a
      divergent method for the synthesis of C- and O-phosphoryl hydroquinone
      derivatives.
AB  - The reaction of P(O)-H compounds with p-quinones could proceed through either 1,4
      or 1,6-addition pathways by employing different additives to selectively give
      the corresponding C- and O-phosphoryl hydroquinone derivatives in good yields.
      Oxidative double 1,4-addition of P(O)-H compounds to p-quinones was also achieved
      by tuning the solvent, affording a facile synthesis of bis-substituted
      hydroquinones with phosphorus functionality. Further studies on these reactions
      by using optically active H-phosphinates showed that all addition reactions took
      place stereospecifically with retention of configuration at the phosphorus
      center. The findings lead to the establishment of a divergent method for the
      synthesis of C- and O-phosphoryl hydroquinone derivatives from easily available
      P(O)-H compounds.

PMID- 23143866
TI  - Burden of emergency and non-emergency colorectal cancer surgeries in West
      Virginia and the USA.
AB  - PURPOSE: Elective surgical resection is the curative treatment for colorectal
      cancer (CRC). Up to 30 % of patients present as surgical emergencies. The
      objective was to determine the association between presenting with an emergency
      condition and consequent outcomes of CRC surgery in the Appalachian state of West
      Virginia (WV) in comparison to the rest of the USA. METHODS: Patients diagnosed
      with CRC who underwent a surgical procedure from January 1, 2003 to December 31,
      2007 were selected, and those with a diagnosis requiring emergency surgery were
      identified. Primary outcome measures were length of stay (LOS), total hospital
      charges, and inpatient death. RESULTS: Mean LOS was higher for WV. Mean charges
      were higher for the USA than for WV. Inpatient deaths in WV were greater than the
      rest of the USA. Those undergoing emergency surgery spent 51.9 % (beta=0.40) more
      days in the hospital than those who did not. For WV, LOS was 7.6 % (beta=0.07)
      higher than that of the US. Hospital charges for those that underwent emergency
      resection were 68.3 % (beta=0.52) higher than those who did not. The odds of in
      hospital death were 1.68 (95 % CI=1.42-1.98) times greater in WV than in the USA.
      Those that underwent emergency surgery had a nearly four times (OR 3.88; 95 %
      CI=3.74-4.03) greater chance of in-hospital death. CONCLUSIONS: The study
      stresses the ongoing burden of emergency surgeries in many states around the
      nation and the need to increase awareness about CRC screening practices,
      especially in patients who are at increased risk of the disease.

PMID- 23143867
TI  - Push enteroscopy: a useful diagnostic modality for proximal small-bowel mass
      lesions.

PMID- 23143868
TI  - The natural history of antismoking advertising recall: the influence of
      broadcasting parameters, emotional intensity and executional features.
AB  - BACKGROUND: The necessary first steps for televised media campaign effects are
      population exposure and recall. To maximise the impact of campaign funding, it is
      critical to identify modifiable factors that increase the efficiency of an
      advertisement reaching the target audience and of their recalling that
      advertisement. METHODS: Data come from a serial cross-sectional telephone survey
      with weekly interviews of adult smokers and recent quitters from the state of New
      South Wales, Australia, collected between April 2005 and December 2010 (total
      n=13 301). Survey data were merged with commercial TV ratings data (Gross Rating
      Points (GRPs)) to estimate individuals' exposure to antismoking campaigns.
      RESULTS: Multivariable logistic regression analyses indicated that GRPs and
      broadcasting recency were positively associated with advertisement recall, such
      that advertisements broadcast more at higher levels or in more recent weeks were
      more likely to be recalled. Advertisements were more likely to be recalled in
      their launch phase than in following periods. Controlling for broadcasting
      parameters, advertisements higher in emotional intensity were more likely to be
      recalled than those low in emotion; and emotionally intense advertisements
      required fewer GRPs to achieve high levels of recall than lower emotion
      advertisements. There was some evidence for a diminishing effect of increased
      GRPs on recall. CONCLUSIONS: In order to achieve sufficient levels of population
      recall of antismoking campaigns, advertisements need to be broadcast at adequate
      levels in relatively frequent cycles. Advertisements with highly emotional
      content may offer the most efficient means by which to increase population
      recall.

PMID- 23143869
TI  - Change in tobacco excise policy in Bulgaria: the role of tobacco industry
      lobbying and smuggling.
AB  - OBJECTIVES: To examine how transnational tobacco companies (TTCs) tried to
      penetrate the Bulgarian cigarette market and influence tobacco excise tax policy
      after the fall of communism and during Bulgaria's accession to the European Union
      (EU). DESIGN: Analysis of internal tobacco industry documents supplemented by
      analysis of press coverage, tobacco industry journals, market reports and key
      informant interviews. RESULTS: TTCs have been involved in cigarette smuggling to
      and through Bulgaria since at least 1975 and used smuggling as a market-entry
      strategy. National tobacco company Bulgartabac appears to have been involved in
      smuggling its own cigarettes from and reimporting them to Bulgaria. Since
      Bulgaria's accession to the EU opened the market to the TTCs, TTCs have
      exaggerated the scale of the illicit trade to successfully convince politicians
      and public health experts that tax increases lead to cigarette smuggling. Yet,
      sources point to TTCs' continued complicity in cigarette smuggling to and through
      Bulgaria between 2000 and 2010. TTCs aimed to influence the Bulgarian tobacco
      excise tax regime, import duties and pricing mechanism, but appear to have been
      less successful than in other former communist countries in part due to the co
      existence of a state-owned tobacco company. Undisclosed meetings between the
      tobacco industry and government ministers and officials are ongoing despite
      Bulgaria being a party to the Framework Convention on Tobacco Control (FCTC).
      CONCLUSIONS: The TTCs continued involvement in smuggling suggests that deals in
      2004, 2007 and 2010 which the European Commission has reached with TTCs to
      address cigarette smuggling are inadequate. The TTCs' continued access to
      policymakers suggests that the FCTC is not being properly implemented.

PMID- 23143870
TI  - SARS-like virus in the Middle East: a truly bat-related coronavirus causing human
      diseases.

PMID- 23143871
TI  - Specification of functional neurons and glia from human pluripotent stem cells.
AB  - Human pluripotent stem cells (PSCs) such as embryonic stem cells (ESCs) and
      induced pluripotent stem cells (iPSCs) hold great promise in regenerative
      medicine as they are an important source of functional cells for potential cell
      replacement. These human PSCs, similar to their counterparts of mouse, have the
      full potential to give rise to any type of cells in the body. However, for the
      promise to be fulfilled, it is necessary to convert these PSCs into functional
      specialized cells. Using the developmental principles of neural lineage
      specification, human ESCs and iPSCs have been effectively differentiated to
      regional and functional specific neurons and glia, such as striatal gama
      aminobutyric acid (GABA)-ergic neurons, spinal motor neurons and myelin sheath
      forming oligodendrocytes. The human PSCs, in general differentiate after the
      similar developmental program as that of the mouse: they use the same set of cell
      signaling to tune the cell fate and they share a conserved transcriptional
      program that directs the cell fate transition. However, the human PSCs, unlike
      their counterparts of mouse, tend to respond divergently to the same set of
      extracellular signals at certain stages of differentiation, which will be a
      critical consideration to translate the animal model based studies to clinical
      application.

PMID- 23143872
TI  - Structural insights into the assembly of human translesion polymerase complexes.
AB  - In addition to DNA repair pathways, cells utilize translesion DNA synthesis (TLS)
      to bypass DNA lesions during replication. During TLS, Y-family DNA polymerase
      (Poleta, Polkappa, Poli and Rev1) inserts specific nucleotide opposite preferred
      DNA lesions, and then Polzeta consisting of two subunits, Rev3 and Rev7, carries
      out primer extension. Here, we report the complex structures of Rev3-Rev7
      Rev1(CTD) and Rev3-Rev7-Rev1(CTD)-Polkappa(RIR). These two structures demonstrate
      that Rev1(CTD) contains separate binding sites for Polkappa and Rev7. Our BIAcore
      experiments provide additional support for the notion that the interaction
      between Rev3 and Rev7 increases the affinity of Rev7 and Rev1. We also verified
      through FRET experiment that Rev1, Rev3, Rev7 and Polkappa form a stable
      quaternary complex in vivo, thereby suggesting an efficient switching mechanism
      where the "inserter" polymerase can be immediately replaced by an "extender"
      polymerase within the same quaternary complex.

PMID- 23143874
TI  - Top-down fabricated silicon-nanowire-based field-effect transistor device on a
      (111) silicon wafer.
AB  - The unique anisotropic wet-etching mechanism of a (111) silicon wafer facilitates
      the highly controllable top-down fabrication of silicon nanowires (SiNWs) with
      conventional microfabrication technology. The fabrication process is compatible
      with the surface manufacturing technique, which is employed to build a nanowire
      based field-effect transistor structure on the fabricated SiNW.

PMID- 23143873
TI  - Proteolytic processing of SDF-1alpha by matrix metalloproteinase-2 impairs CXCR4
      signaling and reduces neural progenitor cell migration.
AB  - Neural stem cells and neural progenitor cells (NPCs) exist throughout life and
      are mobilized to replace neurons, astrocytes and oligodendrocytes after injury.
      Stromal cell-derived factor 1 (SDF-1, now named CXCL12) and its receptor CXCR4,
      an alpha-chemokine receptor, are critical for NPC migration into damaged areas of
      the brain. Our previous studies demonstrated that immune activated and/or HIV-1
      infected human monocyte-derived-macrophages (MDMs) induced a substantial increase
      of SDF-1 production by human astrocytes. However, matrix metalloproteinase (MMP)
      2, a protein up-regulated in HIV-1-infected macrophages, is able to cleave four
      amino acids from the N-terminus of SDF-1, resulting in a truncated SDF-1(5-67).
      In this study, we investigate the diverse signaling and function induced by SDF
      1alpha and SDF-1(5-67) in human cortical NPCs. SDF-1(5-67) was generated by
      incubating human recombinant SDF-1alpha with MMP-2 followed by protein
      determination via mass spectrometry, Western blotting and ELISA. SDF-1alpha
      induced time-dependent phosphorylation of extracellular signal-regulated kinases
      (ERK) 1/2, Akt-1, and diminished cyclic adenosine monophosphate (cAMP). In
      contrast, SDF-1(5-67) failed to induce these signaling. SDF-1alpha activation of
      CXCR4 induced migration of NPCs, an effect that is dependent on ERK1/2 and Akt-1
      pathways; whereas SDF-1(5-67) failed to induce NPC migration. This observation
      provides evidence that MMP-2 may affect NPC migration through post-translational
      processing of SDF-1alpha.

PMID- 23143875
TI  - Helium nanodroplet isolation spectroscopy and ab initio calculations of HO3-(O2)n
      clusters.
AB  - HO3-(O2)n clusters are formed by the sequential addition of the hydroxyl radical
      and O2 molecules to superfluid helium nanodroplets. IR laser spectroscopy in the
      fundamental OH stretching region reveals the presence of several bands assigned
      to species as large as n=4. Detailed ab initio calculations are carried out for
      multiple isomers of cis- and trans-HO3-O2, corresponding to either hydrogen- or
      oxygen-bonded van der Waals complexes. Comparisons to theory suggest that the
      structure of the HO3-O2 complex formed in helium droplets is a hydrogen-bonded
      (4)A' species consisting of a trans-HO3 core. The computed binding energy of the
      complex is approximately 240 cm(-1). Despite the weak interaction between trans
      HO3 and O2, nonadditive redshifts of the OH stretching frequency are observed
      upon successive solvation by O2 to form larger clusters with n>1.

PMID- 23143876
TI  - Access to ordered porous molybdenum oxycarbide/carbon nanocomposites.

PMID- 23143877
TI  - Bilateral fractures of the hook of the hamate: a bicycle handlebar injury.

PMID- 23143878
TI  - Graphene oxide sheath on Ag nanoparticle/graphene hybrid films as an
      antioxidative coating and enhancer of surface-enhanced Raman scattering.
AB  - Surface-enhanced Raman scattering (SERS) has been extensively investigated since
      its discovery on rough Ag surface because of high sensitivity and resolution. Ag
      nanostructures are considered highly active for SERS but their liability to
      oxidization impedes their practical applications as a SERS-based sensing
      platform. Here, we show that graphene oxide (GO) coating on the polyallylamine
      hydrochloride (PAA) functionalized Ag nanoparticles (PAA-AgNP) immobilized on PAA
      functionalized reduced GO (PAA-RGO) films (GO/PAA-AgNP/PAA-RGO, sandwich
      structure) protect AgNPs from oxidation under ambient condition for prolonged
      time up to 72 days with increased and reproducible SERS signals and fast
      adsorption kinetics of rhodamine 6G, a model Raman probe molecule. The present
      strategy for GO coating on top of the immobilized AgNPs will be useful for the
      development of an efficient SERS-based chemical and biosensor because of its
      simplicity, cost-effectiveness, long-term stability, and high reproducibility.

PMID- 23143879
TI  - Chondromodulin-I derived from the inner meniscus prevents endothelial cell
      proliferation.
AB  - The meniscus is a fibrocartilaginous tissue that plays an important role in
      controlling complex biomechanics of the knee. A perimeniscal capillary plexus
      supplies the outer meniscus, whereas the inner meniscus is composed of avascular
      tissue. Anti-angiogenic molecules, such as chondromodulin-I (ChM-I) and
      endostatin, have pivotal roles in preserving the avascularity of cartilage.
      However, the anti-angiogenic role of ChM-I is unclear in the meniscus. We
      hypothesized that the inner meniscus might maintain its avascular feature by
      expressing ChM-I. Immunohistochemical analyses revealed that ChM-I was mainly
      detected in the inner and superficial zones of the meniscus. On the other hand,
      endostatin distribution was similar between the inner and outer meniscus. In
      Western blot, ChM-I was detected only in the inner meniscus, whereas endostatin
      was equally observed in both inner and outer menisci. In addition, ChM-I
      concentration of the inner meniscus-derived conditioned medium was higher than
      that of the outer meniscus-derived medium. ChM-I removal from the inner meniscus
      derived medium and functional blocking of ChM-I significantly increased
      endothelial cell proliferation. In this study, we demonstrated that the inner
      meniscus contained larger amounts of ChM-I, and that the inner meniscus-derived
      ChM-I inhibited endothelial cell proliferation. Our results suggest that ChM-I
      may be a key anti-angiogenic factor for maintaining the avascularity of the inner
      meniscus.

PMID- 23143880
TI  - Performance of independent dose calculation in helical tomotherapy:
      implementation of the MCSIM code.
AB  - Currently, a software-based second check dose calculation for helical tomotherapy
      (HT) is not available. The goal of this study is to evaluate the dose calculation
      accuracy of the in-house software using EGS4/MCSIM Monte Carlo environment
      against the treatment planning system calculations. In-house software was used to
      convert HT treatment plan information into a non-helical format. The MCSIM dose
      calculation code was evaluated by comparing point dose calculations and dose
      profiles against those from the HT treatment plan. Fifteen patients, representing
      five treatment sites, were used in this comparison. Point dose calculations
      between the HT treatment planning system and the EGS4/MCSIM Monte Carlo
      environment had percent difference values below 5 % for the majority of this
      study. Vertical and horizontal planar profiles also had percent difference values
      below 5 % for the majority of this study. Down sampling was seen to improve speed
      without much loss of accuracy. EGS4/MCSIM Monte Carlo environment showed good
      agreement with point dose measurements, compared to the HT treatment plans.
      Vertical and horizontal profiles also showed good agreement. Significant time
      saving may be obtained by down-sampling beam projections. The dose calculation
      accuracy of the in-house software using the MCSIM code against the treatment
      planning system calculations was evaluated. By comparing point doses and dose
      profiles, the EGS4/MCSIM Monte Carlo environment was seen to provide an accurate
      independent dose calculation.

PMID- 23143881
TI  - Protective effects of BDNF overexpression bone marrow stromal cell
      transplantation in rat models of traumatic brain injury.
AB  - Bone marrow stromal cells (MSCs) were used as cell therapy for various diseases
      in recent years. Some reports showed that transplanted MSCs promote functional
      recovery in animal models of brain trauma. But other studies indicate that tissue
      replacement by this method may not be the main source of therapeutic benefit.
      Neurotrophic factors such as brain-derived neurotrophic factor (BDNF) therapeutic
      potential may contribute to the recovery of function after trauma. Our previous
      study showed that BDNF-MSCs could promote the survival of neurons in neuronal
      injured models in vitro. The present study was undertaken to explore the
      therapeutic effects of MSCs transfected with BDNF in vivo. After intraventricular
      injection of MSCs-BDNF, BDNF levels were increased significantly in cerebrospinal
      fluid by ELISA. Further studies showed that treatment of traumatic brain injury
      with MSCs-BDNF could attenuate neuronal injury as measurement of biological
      behavior assessment. These studies demonstrate that by increasing the brain
      concentration of BDNF, intraventricularly transplanted MSCs-BDNF might play an
      important role in the treatment of traumatic brain injury and might be an
      optional therapeutic strategy.

PMID- 23143882
TI  - Sonographic weight estimation in fetuses with congenital diaphragmatic hernia.
AB  - PURPOSE: To determine the accuracy of sonographic weight estimation (WE) for
      fetuses with congenital diaphragmatic hernia (CDH), and to assess whether certain
      sonographic models perform better than others in cases of CDH. MATERIAL AND
      METHODS: In a retrospective, multicenter cohort study, the accuracy of WE in
      fetuses with CDH (n = 172) was evaluated using eight sonographic models and was
      compared with a control group of fetuses without malformations (n = 172). Each
      fetus underwent ultrasound examination with complete biometric parameters within
      7 days of delivery. The accuracy of the different formulas was compared using
      means of percentage errors (MPE), medians of absolute percentage errors (MAPE),
      and proportions of estimates within 10 % of actual birth weight. RESULTS: Fetuses
      with CDH had a significantly lower abdominal circumference (AC) in comparison
      with the control group (293.6 vs. 312.0 mm, p < 0.001). All of the formulas
      tested in fetuses with CDH, except for the Siemer equation (the only model that
      does not incorporate any abdominal measurements), showed significantly lower
      (more negative) MPEs, larger MAPEs, and smaller proportions of estimates within
      10 % of actual birth weight in comparison with the control group.  CONCLUSION:
      The accuracy of sonographic WE in fetuses with CDH is significantly poorer than
      in fetuses without malformations, principally because of a larger systematic
      error due to artificially small AC measurements. The development of new, specific
      models derived from fetuses with CDH could improve the accuracy of WE for infants
      with this condition.

PMID- 23143883
TI  - Ultrasound guided cryoablation of fibroadenomas.
AB  - PURPOSE: Fibroadenoma (FA) of the breast is the most common disorders in young
      women. The aim of the study was to evaluate cryoablation (CA) under ultrasound
      guidance in the office setting for patients with FA. MATERIALS AND METHODS: For
      this prospective multicenter trial an office-based cryosurgical system was used
      to treat histological confirmed benign FA with a maximum dimension of 3 cm. 23 CA
      procedures were performed under ultrasound guidance. The cryoprobe was inserted
      into the center of the FA guided by real-time ultrasound. A freeze-thaw-freeze
      treatment cycle was performed according to the size of the FA. During the CA
      procedure continuous ultrasound monitoring of the ice ball was performed,
      verifying engulfment of the FA. Patients attended 4 follow-up visits at 1 week, 3
      months, 6 months and 1 year and underwent ultrasound and physical examinations.
      RESULTS: Data was collected from 23 procedures. The ice ball engulfed the treated
      FA in 91.3 %. A sharp reduction in volume was observed at 6-month follow-up and
      continued more moderately up to 1 year. No serious but four minor adverse events
      occurred. At 1 year follow-up, lumps that were assessed pre-treatment as hard
      were assessed as soft or not palpable. 7 patients complained of pain caused by
      the lump prior to cryotherapy, while 5 of these patients felt transient pain
      during the follow up period. It is reasonable to assume that the pain was not
      related to the CA procedure as it was not consistent. In 96 % of the cases
      patients and physicians rated the cosmetic results of the procedure as excellent
      or good. CONCLUSION: The cryodestruction proved functional and safe, while
      showing reduction in palpability and pain caused by the FA in the treated
      patients.

PMID- 23143884
TI  - Ultrasound pathology of the elbow: a pictorial essay.

PMID- 23143885
TI  - Waist circumference, BMI, and lung function in 8-year-old children: the PIAMA
      birth cohort study.
AB  - BACKGROUND: Body mass index (BMI) and waist circumference (WC) may be associated
      with lung function in children, as observed in adults. METHODS: Height, weight,
      waist circumference, and lung function (FVC and FEV1 ) were measured during a
      medical examination in 1,058 eight-year-old children participating in the
      Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study.
      RESULTS: After adjusting for height, age and other potential confounders large WC
      or high BMI (>90th percentile) were not associated with forced expiratory volume
      in 1 sec (FEV1) or forced vital capacity (FVC). In girls only, large WC was,
      independently of BMI, associated with 3.5% (95% confidence interval (CI): -6.4, 
      0.6) lower FEV1 /FVC ratio in the model including WC and BMI. Girls with low BMI
      (<10th percentile) had 4.6% lower FEV1 (95% CI: -8.4, -0.6) and 5.1% lower FVC
      (95% CI: -8.8, -1.2) than girls with normal BMI. In boys, we did not observe
      associations between low or high BMI and lung function independent of WC, or
      between small or large WC and lung function after adjustment for BMI. CONCLUSION:
      At 8 years of age, a high BMI or large WC are not yet associated with FEV1 and
      FVC, indicating that this association may change over the course of life from
      childhood to adulthood.

PMID- 23143886
TI  - Experimental and theoretical studies on the bismuth-triflate-catalysed
      cycloisomerisation of 1,6,10-trienes and aryl polyenes.
AB  - Cycloisomerisation of polyenes such as diethyl geranylprenylmalonate [(E)-1 a],
      diethyl geranylphenylmalonate [(E)-2 a] and diethyl cinnamylgeranylmalonate
      [(E,E)-3 a] catalysed by bismuth triflate was studied from experimental and
      theoretical viewpoints. Several intermediates were isolated and characterised,
      and calculated transition-state structures are proposed for the three reactions.
      The diastereoselectivity observed during the reaction of (E)- or (Z)-2 a in
      favour of the formation of trans-fused bicyclic products is discussed in detail.
      The nature of the active catalytic species derived from bismuth triflate was also
      investigated, and the formation of a hybrid Lewis acid/Bronsted acid catalyst
      with water molecules is proposed, supported by experimental and theoretical data.

PMID- 23143887
TI  - Helium implantation effects on the compressive response of Cu nanopillars.
AB  - A fabrication methodology for 120 nm-diameter, <111>-oriented single crystalline
      Cu nanopillars which are uniformly implanted with helium is described. Uniaxial
      compression experiments reveal that their yield strength is 30% higher than that
      of their unimplanted counterparts. This study sheds light on the fundamental
      understanding of the deformation mechanism of irradiated metallic nanocrystals,
      and has important implications for the interplay between irradiation-induced
      defects and the external sample dimensions in the nanoscale.

PMID- 23143888
TI  - Assemblies at the liquid-solid interface: chirality expression from molecular
      conformers.

PMID- 23143889
TI  - The overexpression of SIRT1 inhibited osteoarthritic gene expression changes
      induced by interleukin-1beta in human chondrocytes.
AB  - In this study, we examined the effects of overexpression of SIRT1 on IL-1beta
      induced gene expression changes in human chondrocytes to explore a protective
      role of SIRT1 in human chondrocytes. SIRT1 was overexpressed in human
      chondrocytes by expression plasmid under stimulation with IL-1beta. SIRT1 was
      also inhibited by siRNA under stimulation with IL-1beta. Gene expression changes
      were examined by real-time PCR. The interaction of SIRT1 and p65 (NF-kappaB) were
      examined by Western blotting. SIRT1, MMP-13, and ADAMTS-5 expressions in human
      cartilage were examined by immunohistochemistry. IL-1beta stimulation
      significantly up-regulated MMP-1, 2, 9, and 13 and ADAMTS-5. Overexpression of
      SIRT1 significantly inhibited the up-regulation of those genes caused by IL-1beta
      while the inhibition of SIRT1 further increased them. In addition, the
      overexpression of SIRT1 markedly reduced the IL-1beta-induced acetylation of p65.
      SIRT1 expression was clearly detected in the non-OA cartilage while MMP-13 and
      ADAMTS-5 were undetectable. In contrast, in the OA cartilage, SIRT1 expression
      was decreased while MMP-13 and ADAMTS-5 were increased. Our observations
      suggested that SIRT1 can play a protective role by suppressing IL-1beta-induced
      expressions of cartilage-degrading enzymes partially through the modulation of
      the NF-kappaB pathway. SIRT1 overexpression might be a new therapeutic approach
      for OA.

PMID- 23143890
TI  - Adiponectin (ADIPOQ) rs2241766 G/T polymorphism is associated with risk of
      cancer: evidence from a meta-analysis.
AB  - Associations between adiponectin (ADIPOQ) genetic polymorphisms (rs2241766 G/T
      and rs266729 G/C) and cancer risk have been extensively studied in the past
      decade, while conflicting results were reported. Therefore, this study would
      explore the associations by using a meta-analysis. The databases of Medline,
      Embase, and Wangfang were retrieved, and the latest updated time was 1 August
      2012. Effect sizes of odds ratio and 95 % confidence interval (OR and 95 % CI)
      were calculated by using a fixed- or random-effect model. A total of 12 studies
      with 10,368 participants were identified for association between ADIPOQ rs2241766
      G/T and risk of cancer, and ten studies with 12,665 participants were for
      association between ADIPOQ rs266729 G/C and risk of cancer. Overall combined
      analyses indicated that neither ADIPOQ rs2241766 G/T nor rs266729 G/C was
      associated with risk of cancer incidence (OR (95 % CI), 0.89 (0.61-1.30) for GG
      vs. TT and 0.94 (0.83-1.06) for G carriers vs. T carriers for rs2241766 G/T; 0.99
      (0.85-1.16) for GG vs. CC and 0.96 (0.87-1.06) for G carriers vs. C carriers for
      rs266729 G/C). When stratified analyses were conducted according to the
      participants' ethnicity, sources of controls, types of cancer, and sample size,
      we found that G allele of ADIPOQ rs2241766 G/T was significantly associated with
      decreased risk of cancer based on population-based case-control studies (OR (95 %
      CI), 0.65 (0.50-0.85) for GG vs. TT and 0.88 (0.79-0.98) for G carriers vs. T
      carriers). In contrast, there was no association between rs266729 G/C
      polymorphism and risk of cancer when subgroup analyses were conducted. In
      summary, this meta-analysis indicated that ADIPOQ rs2241766 G/T rather than
      rs266729 G/C polymorphism was closely associated with risk of cancer development.

PMID- 23143891
TI  - Metabolic pathways of inhaled glucocorticoids by the CYP3A enzymes.
AB  - Asthma is one of the most prevalent diseases in the world, for which the mainstay
      treatment has been inhaled glucocorticoids (GCs). Despite the widespread use of
      these drugs, approximately 30% of asthma sufferers exhibit some degree of steroid
      insensitivity or are refractory to inhaled GCs. One hypothesis to explain this
      phenomenon is interpatient variability in the clearance of these compounds. The
      objective of this research is to determine how metabolism of GCs by the CYP3A
      family of enzymes could affect their effectiveness in asthmatic patients. In this
      work, the metabolism of four frequently prescribed inhaled GCs, triamcinolone
      acetonide, flunisolide, budesonide, and fluticasone propionate, by the CYP3A
      family of enzymes was studied to identify differences in their rates of clearance
      and to identify their metabolites. Both interenzyme and interdrug variability in
      rates of metabolism and metabolic fate were observed. CYP3A4 was the most
      efficient metabolic catalyst for all the compounds, and CYP3A7 had the slowest
      rates. CYP3A5, which is particularly relevant to GC metabolism in the lungs, was
      also shown to efficiently metabolize triamcinolone acetonide, budesonide, and
      fluticasone propionate. In contrast, flunisolide was only metabolized via CYP3A4,
      with no significant turnover by CYP3A5 or CYP3A7. Common metabolites included
      6beta-hydroxylation and Delta(6)-dehydrogenation for triamcinolone acetonide,
      budesonide, and flunisolide. The structure of Delta(6)-flunisolide was
      unambiguously established by NMR analysis. Metabolism also occurred on the D-ring
      substituents, including the 21-carboxy metabolites for triamcinolone acetonide
      and flunisolide. The novel metabolite 21-nortriamcinolone acetonide was also
      identified by liquid chromatography-mass spectrometry and NMR analysis.

PMID- 23143892
TI  - A perspective on the contribution of metabolites to drug-drug interaction
      potential: the need to consider both circulating levels and inhibition potency.
AB  - The 2012 drug-drug interaction (DDI) guidance from the European Medicines Agency
      (EMA) and the draft DDI guidance from the Food and Drug Administration (FDA) have
      proposed that metabolites present at >25% of the parent area under the time
      concentration curve (AUC) (EMA and FDA) and >10% of the total drug-related
      exposure (EMA) should be investigated in vitro for their DDI potential. This
      commentary attempts to rationalize the clinically relevant levels of
      metabolite(s) that contribute to DDI by considering not only the abundance but
      also inhibition potency, physicochemical properties, and structural alerts of the
      metabolite. A decision tree is proposed for levels of metabolites that could
      trigger in vitro DDI assessment. When the parent is an inhibitor of cytochrome
      P450s (P450s), clinical DDI studies will assess the in vivo DDI effect of the
      combination of parent and metabolite(s). When the parent is not a P450 inhibitor,
      it is important to assess the inhibition potential of abundant metabolites in
      vitro. The proposal is to apply a default cutoff value of metabolite level which
      is 100% of the parent AUC. It is important to note that exceptions can occur, and
      different metabolite levels may be considered depending on the physiochemical
      properties of metabolites (e.g., increased lipophilicity) and whether the
      metabolite contains structural alerts for DDI (e.g., mechanism-based inhibition).
      A key objective of this commentary is to stimulate discussions among the
      scientific community on this important topic, so that appropriate in vitro
      metabolism studies are conducted on metabolites, to ensure the safety of drugs in
      development balanced with the desire to avoid creating unnecessary studies that
      will add little to no value in ensuring patient safety.

PMID- 23143893
TI  - Extracellular signal-regulated kinase 5 in the cerebrospinal fluid-contacting
      nucleus contributes to morphine physical dependence in rats.
AB  - The cerebrospinal fluid-contacting nucleus (CSF-CN) may influence actual
      composition of the CSF for non-synaptic signal transmission via releasing or
      absorbing bioactive substances, which distributes and localizes in the ventral
      periaqueductal central gray of the brainstem. Previous studies demonstrated that
      CSF-CN was involved in neuropathic pain and morphine dependence. Thus, to
      identify whether extracellular signal-regulated kinase 5 (ERK5) distributed in
      the CSF-CN and its function on the formation and development of morphine physical
      dependence, morphine withdrawal-like behavioral test and immunofluorescent
      technique were used in this research. Morphine was subcutaneously injected by an
      intermittent and escalating procedure to induce physical dependence, which was
      measured by withdrawal symptoms. In this study, we found that horseradish
      peroxidase-conjugated toxin subunit B/p-ERK5 double-labeled neurons expressed in
      the CSF-CN of normal rats. ERK5 signaling pathway was remarkably activated by
      naloxone-precipitated withdrawal in the CSF-CN. Moreover, selective attenuation
      of p-ERK5 expression in the CSF-CN by lateral ventricle injection of BIX02188
      could significantly relieve morphine withdrawal symptom. These findings confirmed
      that the activation of p-ERK5 in the CSF-CN might contribute to morphine physical
      dependence.

PMID- 23143894
TI  - Inversion time prolongation at late enhancement cardiac MRI in a myeloma patient.
AB  - A patient undergoing chemotherapy for multiple myeloma had a sudden onset of
      heart failure. Cardiac magnetic resonance was performed after echocardiography to
      rule out  myocardial late enhancement, which was not detected. In- terestingly,
      the inversion time of the T1-weighted inversion recovery late enhancement
      sequence needed to be significantly increased (from the usual 250-300 to 490 ms)
      to obtain diagnostic images. This report presents the clinical case of this
      patient, and discusses potential implications.

PMID- 23143895
TI  - Coupling Dy3 triangles to maximize the toroidal moment.

PMID- 23143896
TI  - Process model comparison and transferability across bioreactor scales and modes
      of operation for a mammalian cell bioprocess.
AB  - A Monod kinetic model, logistic equation model, and statistical regression model
      were developed for a Chinese hamster ovary cell bioprocess operated under three
      different modes of operation (batch, bolus fed-batch, and continuous fed-batch)
      and grown on two different bioreactor scales (3 L bench-top and 15 L pilot
      scale). The Monod kinetic model was developed for all modes of operation under
      study and predicted cell density, glucose glutamine, lactate, and ammonia
      concentrations well for the bioprocess. However, it was computationally demanding
      due to the large number of parameters necessary to produce a good model fit. The
      transferability of the Monod kinetic model structure and parameter set across
      bioreactor scales and modes of operation was investigated and a parameter
      sensitivity analysis performed. The experimentally determined parameters had the
      greatest influence on model performance. They changed with scale and mode of
      operation, but were easily calculated. The remaining parameters, which were
      fitted using a differential evolutionary algorithm, were not as crucial. Logistic
      equation and statistical regression models were investigated as alternatives to
      the Monod kinetic model. They were less computationally intensive to develop due
      to the absence of a large parameter set. However, modeling of the nutrient and
      metabolite concentrations proved to be troublesome due to the logistic equation
      model structure and the inability of both models to incorporate a feed. The
      complexity, computational load, and effort required for model development has to
      be balanced with the necessary level of model sophistication when choosing which
      model type to develop for a particular application.

PMID- 23143897
TI  - 10-Fold increase (2006-11) in the rate of healthy subjects with extended-spectrum
      beta-lactamase-producing Escherichia coli faecal carriage in a Parisian check-up
      centre.
AB  - OBJECTIVES: In 2006, 0.6% of healthy subjects living in the Paris area had
      extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli in their gut.
      To assess the evolution of this rate, a study identical to that of 2006 was
      conducted in 2011. PARTICIPANTS AND METHODS: Healthy adults who visited the IPC
      check-up centre in February-March 2011 and agreed to participate, provided stools
      and answered a questionnaire on the visit day. Stools were analysed to detect
      ESBL producers and to isolate the dominant E. coli population. ESBLs were
      molecularly characterized. For the subjects harbouring ESBL-producing E. coli,
      the phylogenetic group and sequence type (ST) were determined for both ESBL
      producing and dominant E. coli isolates. PFGE profiles were also determined when
      two types of isolates had the same ST. RESULTS: Among the 345 subjects included,
      21 (6%) had ESBL-producing E. coli faecal carriage. None of the previously
      published risk factors was identified. CTX-M accounted for 86% and SHV-12 for
      14%. Dominant and ESBL-producing E. coli were similarly distributed into
      phylogenetic groups (A, 52%-48%; B1, 5%; B2, 24%-14%; and D, 19%-33%). Dominant
      and ESBL-producing E. coli displayed a polyclonal structure (18 STs each).
      However, ST10 and ST131 were identified in dominant and ESBL-producing E. coli
      isolates from different subjects. Most (20/21) ESBL producers were subdominant
      and belonged (16/21) to STs different from that of the corresponding dominant E.
      coli. CONCLUSIONS: The 10-fold increase in the rate of healthy subjects with ESBL
      producing E. coli faecal carriage over a 5 year period suggests wide
      dissemination of these isolates in the Parisian community.

PMID- 23143898
TI  - Challenges for accurate susceptibility testing, detection and interpretation of
      beta-lactam resistance phenotypes in Pseudomonas aeruginosa: results from a
      Spanish multicentre study.
AB  - OBJECTIVES: To evaluate the proficiency of Spanish laboratories regarding
      accurate susceptibility testing, detection and interpretation of Pseudomonas
      aeruginosa beta-lactam resistance phenotypes. METHODS: Thirteen characterized
      strains were sent to 54 participating centres: clinical strains producing
      horizontally acquired beta-lactamases [extended-spectrum beta-lactamases (ESBLs;
      PER-1 and OXA-161) and class A (GES-5) and B (VIM-2) carbapenemases] and mutants
      with combinations of chromosomal mechanisms (AmpC, OprD and/or efflux). The
      centres were requested to evaluate six antipseudomonal beta-lactams, provide
      raw/interpreted clinical categories and detect/infer the resistance mechanisms.
      Consensus results from reference centres were used to assign minor, major or very
      major errors (mEs, MEs or VMEs). RESULTS: Vitek2, MicroScan WalkAway and Wider
      were the most used devices (25%-30% each). CLSI/EUCAST breakpoints were used in
      86%/14% of the determinations. Discrepancies exclusively due to the differential
      application of breakpoints were highest for aztreonam, followed by
      piperacillin/tazobactam. The lowest percentage of VMEs was for Vitek2, followed
      by Wider. The highest percentages of VMEs (6%) were for the AmpC-hyperproducing
      OprD(-) strain and for the GES-5 producer, while among antibiotics the highest
      percentage of VMEs (22%) involved piperacillin/tazobactam. Appropriate inference
      of resistance mechanisms was high for the VIM-2-producing strain (83%), but low
      (<40%) for strains producing ESBLs or non-metallo-beta-lactamase carbapenemases.
      CONCLUSIONS: The use of different breakpoints and devices, the complexity of
      mutation-driven resistance mechanisms and the lack of unequivocal tests to detect
      ESBLs or carbapenemases in P. aeruginosa leads to extraordinary variability and
      low accuracy in susceptibility testing, which may have consequences for the
      treatment and control of nosocomial infections.

PMID- 23143899
TI  - Darunavir is predominantly unbound to protein in cerebrospinal fluid and
      concentrations exceed the wild-type HIV-1 median 90% inhibitory concentration.
AB  - OBJECTIVES: Higher CSF antiretroviral concentrations may be associated with
      better control of HIV replication and neurocognitive performance, but only the
      unbound fraction of antiretrovirals is available to inhibit HIV. Therefore, the
      objective of this study was to determine total and unbound darunavir
      concentrations in CSF and compare findings with plasma concentrations as well as
      the wild-type HIV-1 90% inhibitory concentration (IC(90)). METHODS: Subjects with
      HIV infection were selected based on the use of darunavir-containing regimens
      with a twice-daily dosing schedule and availability of stored CSF and matched
      plasma. Total darunavir was measured by HPLC for plasma or liquid chromatography
      tandem mass spectroscopy (LC/MS/MS) for CSF. Plasma unbound darunavir was
      measured by ultrafiltration and LC/MS/MS. CSF protein binding was determined by
      competitive binding exchange with radiolabelled darunavir. RESULTS: Twenty-nine
      matched CSF-plasma pairs were analysed and darunavir was detected in all CSF
      specimens (median total concentration 55.8 ng/mL), with a CSF unbound fraction of
      93.5%. Median fractional penetrance was 1.4% of median total and 9.4% of median
      unbound plasma concentrations. Unbound darunavir concentrations in CSF exceeded
      the median IC(90) for wild-type HIV in all subjects by a median of 20.6-fold,
      despite the relatively low fractional penetrance. Total darunavir concentrations
      in CSF correlated with both total and unbound darunavir concentrations in plasma.
      CONCLUSIONS: Darunavir should contribute to the control of HIV replication in the
      CNS as a component of effective combination antiretroviral regimens.

PMID- 23143900
TI  - Epidemiology of the Acinetobacter-derived cephalosporinase, carbapenem
      hydrolysing oxacillinase and metallo-beta-lactamase genes, and of common
      insertion sequences, in epidemic clones of Acinetobacter baumannii from Spain.
AB  - OBJECTIVES: To study the distribution, diversity and activity of Acinetobacter
      derived cephalosporinase (ADC)-, carbapenem-hydrolysing oxacillinase (CHO)- and
      metallo-beta-lactamase (MBL)-encoding genes, and of the most common insertion
      sequences (ISs), in the genome of nosocomial, epidemic, multidrug-resistant
      Acinetobacter baumannii (MDRAB) clones from Spain. METHODS: The studied
      population included 59 MDRAB strains previously genotyped by PFGE and multilocus
      sequence typing. The search for the ADC (bla(ADC)), CHO (bla(OXA-51-like),
      bla(OXA-23-like), bla(OXA-40-like) and bla(OXA-58-like)) and MBL (bla(IMP),
      bla(VIM), bla(SIM-1), bla(GIM-1), bla(SPM-1) and bla(NDM-1)) genes, and for the
      ISs (ISAba1, ISAba2, ISAba3, ISAba4 and IS18) was done by PCR assays. The
      phenotypic presence of MBL enzymes was examined using imipenem/imipenem + EDTA
      strips. RESULTS: The most prevalent IS, ISAba1 (93.2%), was detected upstream of
      bla(ADC) and bla(OXA-51-like). These genes showed ample diversity (10 and 8
      alleles, respectively). Four ADC sequences (ADC-1-like(P240S), ADC-2
      like(N260H/T264N), ADC-11-like(Q163K) and ADC-11-like(G342R)) are described here
      for the first time. bla(OXA-58-like) was carried by 20.3% of strains, in
      association with ISAba2, ISAba3 or IS18. bla(OXA-40-like) was the most prevalent
      acquired CHO gene (57.6%), and was associated with none of the studied ISs.
      Neither bla(OXA-23-like) nor ISAba4 was detected in any strain. Some 67.8% of
      strains with MBL activity showed no corresponding gene in PCR; these results were
      more common in strains with a highly active CHO, such as OXA-40. CONCLUSIONS: All
      the studied genes and their related ISs showed a clonal distribution. Imipenem
      resistance was probably provided by OXA-40 for the most part, while MBL- and OXA
      23-encoding genes were absent in the studied population.

PMID- 23143901
TI  - Oseltamivir and inhaled zanamivir as influenza prophylaxis in Thai health
      workers: a randomized, double-blind, placebo-controlled safety trial over 16
      weeks.
AB  - OBJECTIVES: Long-term chemoprophylaxis using neuraminidase inhibitors may be
      needed during influenza epidemics but safety data are limited to several weeks.
      We sought to assess the tolerability of oseltamivir and zanamivir as primary
      prophylaxis over 16 weeks. METHODS: We conducted a parallel group, double blind,
      2 (active drug) :1 (placebo) randomized trial of oral oseltamivir/placebo or
      inhaled zanamivir/placebo over 16 weeks in healthy, Thai hospital professionals
      at two Bangkok hospitals. The primary endpoint was study withdrawal due to drug
      related (possibly, probably, definitely) serious or adverse events (AEs) graded
      >= 2. RESULTS: Recruited subjects numbered 129 oseltamivir/65 placebo and 131
      zanamivir/65 placebo. A total of 102 grade >= 2 AEs were reported or detected in
      69 subjects: 23/129 (17.8%) versus 15/65 (23.1%) (P=0.26), and 23/131 (17.6%)
      versus 8/65 (12.3%) (P=0.28). Intercurrent infections/fevers [26/102 (25.5%)],
      abnormal biochemistry [25/102 (24.5%)] and gastrointestinal symptoms [18/102
      (17.6%)] were the most frequently reported AEs. There were no drug-related study
      withdrawals. Eight serious AEs were all due to intercurrent illnesses.
      Laboratory, lung function and ECG parameters were similar between drugs and
      placebos. CONCLUSIONS: Oseltamivir and zanamivir were well tolerated in healthy
      hospital professionals. Both drugs can be recommended for primary influenza
      prophylaxis for up to 16 weeks.

PMID- 23143902
TI  - Effect of the substituents of the neighboring ring in the conformational
      equilibrium of iduronate in heparin-like trisaccharides.
AB  - Based on the structure of the regular heparin, we have prepared a smart library
      of heparin-like trisaccharides by incorporating some sulfate groups in the
      sequence alpha-D-GlcNS- (1-4)-alpha-L-Ido2S-(1-4)-alpha-D-GlcN. According to the
      3D structure of heparin, which features one helix turn every four residues, this
      fragment corresponds to the minimum binding motif. We have performed a complete
      NMR study and found that the trisaccharides have a similar 3D structure to
      regular heparin itself, but their spectral properties are such that allow to
      extract very detailed information about distances and coupling constants as they
      are isotropic molecules. The characteristic conformational equilibrium of the
      central iduronate ring has been analyzed combining NMR and molecular dynamics and
      the populations of the conformers of the central iduronate ring have been
      calculated. We have found that in those compounds lacking the sulfate group at
      position 6 of the reducing end glucosamine, the population of (2)S(0) of the
      central iduronate residue is sensitive to the temperature decreasing to 19% at
      278 K. On the contrary, the trisaccharides with 6-O-sulfate in the reducing end
      glucosamine keep the level of population constant with temperature circa 40% of
      (2)S(0) similar to that observed at room temperature. Another structural feature
      that has been revealed through this analysis is the larger flexibility of the L
      IdoAS- D-GlcN glycosidic linkage, compared with the D-GlcNS-L-IdoA. We propose
      that this is the point where the heparin chain is bended to form structures far
      from the regular helix known as kink that have been proposed to play an important
      role in the specificity of the heparin-protein interaction.

PMID- 23143903
TI  - Horizontal deviation as diagnostic and prognostic values in isolated fourth nerve
      palsy.
AB  - BACKGROUND/AIMS: To investigate the causes of isolated fourth nerve palsy (IFNP)
      and the association among aetiology, prognosis and ocular deviation. METHODS: A
      total of 126 consecutive cases of IFNP was retrospectively reviewed. According to
      aetiologies, all patients were classified into five groups: microvascular,
      congenital, decompensation of congenital, traumatic and others. We investigated
      the recovery rate of IFNP patients who could be followed for more than 6 months
      or until they recovered completely. Patients also had the magnitude of vertical
      and horizontal ocular deviations (prism diopter) measured in the primary eye
      position on the first visit. RESULTS: Major causes of IFNP were microvascular
      (47%) and decompensated (33%). The rate of recovery was significantly different
      between microvascular IFNP and decompensated IFNP (92% vs 55%, p<0.001). There
      were no differences in both age of onset or mean vertical deviation between the
      two aetiologies (68.6+/-9.8 vs 65.4+/-13.3, 5.7+/-3.3 vs 7.8+/-7.9). However, for
      mean horizontal deviation, there was a significant difference between
      microvascular and decompensated IFNP (0.4+/-3.0 vs 4.9+/-5.6, p<0.001). Although
      the fourth nerve abducts the eyeball, 69 of 126 cases (55%) showed exotropia. The
      microvascular IFNP group included more cases of exodeviation, while the
      decompensated IFNP group included more cases of esodeviation (p<0.001).
      CONCLUSIONS: Contrary to previous thinking, the horizontal deviation of IFNP
      mainly showed exodeviation, and the degree of horizontal deviation is useful for
      making a determination between vasculopathic and decompensated IFNP. This
      differentiation could be critical for predicting the outcome.

PMID- 23143904
TI  - Is sunlight exposure a risk factor for age-related macular degeneration? A
      systematic review and meta-analysis.
AB  - BACKGROUND: Epidemiologists have recently investigated sunlight exposure as a
      risk factor for age-related macular degeneration (AMD), but there remains an
      ongoing dispute over this association due to insufficient evidence and unreliable
      data. OBJECTIVES: To analyse comprehensively the epidemiological literature
      concerning the association between AMD and sunlight exposure. METHODS: We
      systematically reviewed the epidemiological literature concerning the association
      between AMD and sunlight exposure. An electronic search was performed of PubMed,
      Web of Science and CNKI, which was supplemented by hand searching. The selection
      of studies, data abstraction and quality assessment were performed independently
      by three reviewers. After these steps, we performed a random-effects meta
      analysis, followed by subgroup analysis and sensitivity analysis, including a
      random-effects meta-regression for study-specific covariates. RESULTS: Fourteen
      studies were identified. Twelve studies identified an increasing risk of AMD with
      greater sunlight exposure, six of which reported significant risks. The pooled OR
      was 1.379 (95% CI 1.091 to 1.745). The subgroup of non-population-based studies
      revealed a significant risk (OR 2.018, 1.248 to 3.265, p=0.004). We identified
      the gross domestic product (GDP) per capita (p=0.048), but not the latitude
      (p=0.21), as a factor that led to heterogeneity according to the meta-regression.
      CONCLUSIONS: The epidemiological literature published to date indicates that
      individuals with more sunlight exposure are at a significantly increased risk of
      AMD. The OR significantly decreased with increasing GDP per capita.

PMID- 23143905
TI  - Fifteen-year mortality rate and visual outcome in newly diagnosed chronic open
      angle glaucoma.

PMID- 23143906
TI  - Effect of refractive status on peripapillary retinal nerve fibre layer thickness:
      a study by RTVue spectral domain optical coherence tomography.
AB  - AIM: To evaluate the influence of axial length on retinal nerve fibre layer
      (RNFL) thickness in myopic, hyperopic and emmetropic eyes by spectral domain
      optical coherence tomography (OCT). METHODS: Subjects were divided into three
      groups: myopic (n=35), emmetropic (n=30) and hyperopic eyes (n=33). RNFL
      thickness was obtained from all octametric section parameters by RTVue OCT. Axial
      length and spherical equivalent values were determined for all patients. RESULTS:
      RNFL thickness values, except for lower and upper nasal sectors, were thinner in
      the myopic eyes than in the hyperopic eyes. Average RNFL thickness and the RNFL
      thicknesses of the superotemporal, superonasal, inferotemporal and lower temporal
      sectors were significantly different between the myopic and emmetropic eyes, and
      average RNFL thickness and the RNFL thicknesses of the upper temporal and
      inferonasal sectors were significantly different between the hyperopic and
      emmetropic eyes. The average peripapillary RNFL thickness had a negative
      correlation with axial length (r=-0.741, p<0.001). However, after correction of
      the magnification effect, the significant differences disappeared. CONCLUSIONS:
      We have shown that axial length/refractive status affected the peripapillary RNFL
      thickness profile measured by RTVue OCT. To make a correct diagnosis for
      glaucoma, either the axial length-induced magnification effect should corrected
      by ophthalmologists or the RTVue OCT database should be improved by taking axial
      length into account.

PMID- 23143907
TI  - Local conjunctival metastases from primary conjunctival melanoma: clinico
      pathological correlation and implications.
AB  - BACKGROUND/AIMS: A retrospective service evaluation identified seven patients who
      developed local conjunctival metastases (LCMs) of the conjunctiva after a primary
      diagnosis of conjunctival invasive melanoma. The study was conducted to identify
      the clinico-pathological characteristics and implications of these LCMs. METHODS:
      Seven patients with primary conjunctival melanoma seen by the ocular oncology
      service were identified as having also developed LCMs. The clinical history,
      histopathology, tumour biology, prognostic and staging implications of LCMs were
      evaluated. RESULTS: A total of 15 primary conjunctival melanomas and 19 LCMs were
      identified. The LCM developed 8-102 months after the first primary melanoma and,
      in three patients, non-conjunctival metastases developed 8-37 months after the
      first LCM. The LCMs showed some distinct histopathological features: they were
      well defined, were separated from the overlying epithelium by a Grenz zone, and
      were often multiple and associated with vessels and sometimes lymphocytic
      aggregates. Some appeared within the confines of the vascular drainage territory
      of the primary melanoma; others did not confine themselves to this distribution.
      CONCLUSIONS: LCMs are local metastases of primary conjunctival melanoma that
      probably develop by dissemination through the local vessels and then becoming
      extavascular. Their accurate histopathological recognition is important, as it
      indicates a higher disease stage-indicating 'N' status within the TNM
      classification and may be a proxy indicator of the presence of non-conjunctival
      metastases, thus necessitating high-resolution radiological imaging modalities or
      sentinel node biopsy. LCMs may represent an under-recognised lesion and may have
      been mistaken for primary 'nodular' conjunctival melanomas in the past.

PMID- 23143908
TI  - Indocyanine green enhanced transpupillary thermotherapy in combination with
      ophthalmic artery chemosurgery for retinoblastoma.
AB  - PURPOSE: Review our experience in the use of indocyanine green (ICG) enhanced
      transpupillary thermotherapy (TTT) in combination with ophthalmic artery
      chemosurgery for retinoblastomas unresponsive to standard TTT. METHODS: Single
      centre, retrospective study of 16 eyes in 13 retinoblastoma patients treated with
      TTT and ICG via indirect ophthalmoscope: 23 treatments of 16 eyes, with a mean
      follow-up of 12.1 months (range 3-35 months). Outcome measures included tumour
      response and electroretinogram. RESULTS: Treatment resulted in significant tumour
      regression in all eyes: 13 eyes with well-differentiated characteristics, 2 with
      implanting vitreous seeds and 1 eye refractory to traditional TTT. ERG function
      was retained in all eyes. CONCLUSIONS: ICG-enhanced TTT with ophthalmic artery
      chemosurgery can effectively treat retinoblastoma refractory to conventional
      focal treatments without deleterious ocular side effects.

PMID- 23143909
TI  - Coexistence of KCNV2 associated cone dystrophy with supernormal rod
      electroretinogram and MFRP related oculopathy in a Turkish family.
AB  - BACKGROUND AND AIM: To describe the clinical and genetic characteristics of a
      mother and her son presenting with two distinct and rare forms of retinal
      degeneration. METHODS: Investigations in both patients comprised spectral domain
      optical coherence tomography (SD-OCT), fundus autofluorescence imaging, non
      contact biometry, ultrasonography, electroretinography (ERG) and analysis of the
      mutational status of the KCNV2 and MFRP genes in genomic DNA. RESULTS: The
      clinical course and typical ERG pattern indicated a 'cone dystrophy with
      supernormal rod electroretinogram' in the proband, and SD-OCT demonstrated a
      subfoveal optical gap with loss of the inner segment/outer segment junction line.
      The proband was homozygous for a c.782C>A (p.Ala261Asp) mutation in KCNV2. Her
      son's axial length was shortened with refractive errors of +16.75 dioptres in the
      right and +14.0 dioptres in the left eye; ERG evidenced a rod-cone dystrophy, OCT
      showed central macular thickening with cystoid changes and ultrasonography
      revealed optic disc drusen. MFRP analysis disclosed a 1 bp deletion (c.498delC)
      that predicts a truncated protein. CONCLUSIONS: Two distinct ocular phenotypes
      with pathogenic mutations in two different genes segregated in this family. The
      coexistence of two independent autosomal recessive disorders should be considered
      even when dealing with diseases that bear low carrier frequencies in the general
      population.

PMID- 23143910
TI  - Does inferior oblique recession cause overcorrections in laterally incomitant
      small hypertropias due to superior oblique palsy?
AB  - AIM: To evaluate the effects of inferior oblique muscle recession (IOR) in cases
      of laterally incomitant hypertropia <10 prism dioptres (PD) in central gaze thact
      2t are clinically consistent with superior oblique palsy (SOP). METHODS: We
      retrospectively reviewed patients with SOP and hypertropias <10 PD in central
      gaze who underwent graded IOR. Primary outcomes were reduction of lateral
      incomitance and number of overcorrections in central gaze. RESULTS: Twenty-five
      patients were included. Mean follow-up was 13.8 months (range 1.4-66). Mean
      central gaze hypertropia decreased from 5.6+/-2.1 to 0.2+/-1.6 PD (p<0.001).
      Contralateral gaze hypertropia decreased from 15.9+/-7.6 to 2.3+/-3.3 PD
      (p<0.001). Lateral incomitance (central vs contralateral gaze) was 10.3+/-6.9 PD
      preoperatively and 2.0+/-3.0 PD postoperatively (p<0.001). There were two
      patients overcorrected in central gaze, and one patient overcorrected in
      downgaze. One patient necessitated further surgery for overcorrection.
      CONCLUSIONS: Although small hypertropias can be treated with prisms or small,
      adjustable inferior rectus recessions, IOR collapses incomitance without causing
      much overcorrection. IOR is a reasonable treatment for small, laterally
      incomitant hypertropia due to SOP.

PMID- 23143911
TI  - Rapid, controllable fabrication of regular complex microarchitectures by
      capillary assembly of micropillars and their application in selectively
      trapping/releasing microparticles.
AB  - A simple strategy to realize new controllable 3D microstructures and a novel
      method to reversibly trapping and releasing microparticles are reported. This
      technique controls the height, shape, width, and arrangement of pillar arrays and
      realizes a series of special microstructures from 2-pillar-cell to 12 cell
      arrays, S-shape, chain-shape and triangle 3-cell arrays by a combined top
      down/bottom up method: laser interference lithography and capillary force-induced
      assembly. Due to the inherent features of this method, the whole time is less
      than 3 min and the fabricated area determined by the size of the laser beam can
      reach as much as 1 cm(2) , which shows this method is very simple, rapid, and
      high-throughput. It is further demonstrated that the 'mechanical hand'-like 4
      cell arrays could be used to selectively trap/release microparticles with
      different sizes, e.g., 1.5, 2, or 3.5 MUm, which are controlled by the period of
      the microstructures from 2.5 to 4 MUm, and 6 MUm. Finally, the 'mechanical hand'
      like 4-cell arrays are integrated into 100 MUm-width microfluidic channels
      prepared by ultraviolet photolithography, which shows that this technique is
      compatible with conventional microfabrication methods for on-chip applications.

PMID- 23143912
TI  - Metal-supported aluminosilicate ultrathin films as a versatile tool for studying
      the surface chemistry of zeolites.
AB  - The application of a variety of "surface-science" techniques to elucidate surface
      structures and mechanisms of chemical reactions at zeolite surfaces has long been
      considered as almost impossible because of the poor electrical and thermal
      conductivity of those materials. Here, we show that the growth of a thin
      aluminosilicate film on a metal single crystal under controlled conditions
      results in adequate and well-defined model systems for zeolite surfaces. In
      principle, silicate films that contain metals other than Al (e.g. Ti, Fe, etc)
      may be prepared in a similar way. We believe that this approach opens up a new
      playground for experimental and theoretical modeling of zeolites, aimed at a
      fundamental understanding of structure-reactivity relationships in such
      materials.

PMID- 23143913
TI  - Estimating working memory capacity for lists of nonverbal sounds.
AB  - Working memory (WM) capacity limit has been extensively studied in the domains of
      visual and verbal stimuli. Previous studies have suggested a fixed WM capacity of
      typically about three or four items, on the basis of the number of items in
      working memory reaching a plateau after several items as the set size increases.
      However, the fixed WM capacity estimate appears to rely on categorical
      information in the stimulus set (Olsson & Poom Proceedings of the National
      Academy of Sciences 102:8776-8780, 2005). We designed a series of experiments to
      investigate nonverbal auditory WM capacity and its dependence on categorical
      information. Experiments 1 and 2 used simple tones and revealed capacity limit of
      up to two tones following a 6-s retention interval. Importantly, performance was
      significantly higher at set sizes 2, 3, and 4 when the frequency difference
      between target and test tones was relatively large. In Experiment 3, we added
      categorical information to the simple tones, and the effect of tone change
      magnitude decreased. Maximal capacity for each individual was just over three
      sounds, in the range of typical visual procedures. We propose that two types of
      information, categorical and detailed acoustic information, are kept in WM and
      that categorical information is critical for high WM performance.

PMID- 23143914
TI  - Sources of bias and uncertainty in a visual temporal individuation task.
AB  - Despite a clear ability to detect temporal modulations of visual stimuli in
      excess of 50 Hz, temporal individuation and serial order judgment tasks can be
      performed only when stimuli alternate at much slower rates, and the nature of
      such sluggishness remains unclear. One example of a task with a slow temporal
      limit is the individuation of a cued letter in a rapid serial visual presentation
      (RSVP) stream. The present study investigates the nature of the code used to
      perform such a slow temporal individuation task and the sources of uncertainty
      involved. The results demonstrate that temporal, rather than ordinal, position in
      the RSVP stream is critical in serial order estimation, suggesting the
      involvement of a noisy temporal code. In addition to variability in temporal
      coding, observers' choices are also limited by a number of other factors, such as
      categorical errors and biases related to the position of the cue in the letters'
      stream. Attentional filtering improves categorization, but crucially, it does not
      seem to increase the temporal precision of judgment. Generalizing the present
      results, I suggest that perception of order is limited by an internal temporal
      sampling instability that is distinct and independent from attention and that,
      similarly to temporal jitter in a clock, acts as a low-pass filter that hinders
      the judgment of the order of events that unfold too quickly.

PMID- 23143915
TI  - The heart beat does not make us tick: the impacts of heart rate and arousal on
      time perception.
AB  - According to popular models of human time perception, variations in prospective
      timing are caused by two factors: the pulse rate of an internal pacemaker and the
      amount of attention directed to the passage of time. The results concerning the
      effect of attention on subjective timing have been conclusive, but the mechanisms
      that drive the pacemaker are still far from being understood. In two experiments,
      we examined the impact of two factors that in the existing literature on human
      time perception have been argued to affect such a pacemaker: arousal and heart
      rate. Experienced arousal and heart rate were varied independently by means of
      specific physical exercises: (a) A muscle exercise increased arousal and heart
      rate; (b) a breath-holding exercise increased arousal but decreased heart rate;
      and (c) in the control condition, arousal and heart rate were held constant. The
      results indicate that increased subjective arousal leads to higher time
      estimates, whereas heart rate itself has no relevant impact on time perception.
      The results are discussed with respect to the underlying mechanisms of
      prospective time perception.

PMID- 23143916
TI  - Top-down task sets for combined features: behavioral and electrophysiological
      evidence for two stages in attentional object selection.
AB  - We studied whether visual search for targets defined by a combination of features
      from different dimensions is guided by separately represented target features or
      by an integrated representation of the target objects. In Experiment 1,
      participants searched for target singleton bars that were defined by a specific
      combination of color (red or blue) and size (small or large). The target arrays
      were preceded by cue arrays that contained a spatially uninformative color/size
      singleton. Behavioral spatial-cueing effects indicative of attentional capture
      were triggered only by cues that matched both target-defining features, but not
      by partially target-matching cues, suggesting that attention was guided by
      integrated object representations. However, the presence of reliable N2pc
      components for partially matching cues demonstrated that these cues did capture
      attention, in line with independent feature-based guidance of attention. This
      dissociation between the electrophysiological and behavioral markers of
      attentional capture was confirmed in Experiment 2, in which targets were defined
      by a color/size disjunction. Our results suggest that the attentional selection
      of targets that are defined by a combination of features is a two-stage process:
      Attention is initially captured by all target-matching features, but is then
      rapidly withdrawn from nontarget objects that share some but not all features
      with the current target.

PMID- 23143917
TI  - Spatial interference between attended items engenders serial visual processing.
AB  - A pair of experiments investigated the architecture of visual processing,
      parallel versus serial, across high and low levels of spatial interference in a
      divided attention task. Subjects made speeded judgments that required them to
      attend to a pair of color-cued objects among gray filler items, with the spatial
      proximity between the attended items varied to manipulate the strength of
      interference between attended items. Systems factorial analysis (Townsend &
      Nozawa, Journal of Mathematical Psychology 39:321-359, 1995) was used to identify
      processing architecture. Experiment 1, using moderately dense displays, found
      evidence of parallel processing whether attended objects were in low or high
      proximity to one another. Experiment 2, using higher-density displays, found
      evidence of parallel selection when attended stimuli were widely separated but
      serial processing when they were in high proximity. Divided visual attention can
      operate in parallel under conditions of low or moderate spatial interference
      between selected items, but strong interference engenders serial processing.

PMID- 23143918
TI  - The ground is dominant in infants' perception of relative distance.
AB  - When making relative distance judgments, adults attend to information provided by
      the ground surface and generally ignore information provided by ceiling surfaces.
      In the present study, we asked whether this ground dominance effect is present in
      infancy. Groups of 5- and 7-month-old infants viewed a display depicting textured
      ground and ceiling surfaces. Two toys, which were attached to vertical rods, were
      affixed to the display. The toys/rods were positioned so that one toy was
      specified as being nearer by the ground surface but farther away by the ceiling
      surface, while the other toy was specified as being farther away by the ground
      surface but nearer by the ceiling surface. Under monocular viewing conditions,
      the infants in both age groups reached preferentially for the toy that was
      specified as being nearer by the ground surface. This effect was significantly
      stronger than that observed under binocular viewing conditions. The findings
      indicate that the infants responded to the distance information provided by the
      ground surface to a greater extent than to information provided by the ceiling.

PMID- 23143919
TI  - In vitro and in vivo evaluation of (L)-lactide/epsilon-caprolactone copolymer
      scaffold to support myoblast growth and differentiation.
AB  - Skeletal muscle regeneration involves the activation of satellite cells to
      myoblasts, followed by their proliferation and fusion to form multinucleated
      myotubes and myofibers. The potential of in vitro proliferated myoblasts to treat
      various diseases and tissue defects can be exploited using tissue-engineering
      principles. With an aim to develop a biocompatible and biodegradable scaffold
      that supports myoblast growth and differentiation, we have developed a porous
      sponge with 70/30 L-lactide/epsilon-caprolactone copolymer (PLC) using a phase
      inversion combined with particulate leaching method. Degradation studies
      indicated that the sponge retained its structural integrity for 5 months in vitro
      and had undergone complete biodegradation within 9 months in vivo. The sponge
      supported human myoblasts attachment and its proliferation. Myoblasts seeded on
      the PLC sponge differentiated and fused in vitro to form myotubes expressing
      myosin heavy chain. Histological and molecular analyses of the PLC scaffolds
      seeded with green fluorescent protein-labeled human myoblasts and implanted
      ectopically under the skin in SCID mice demonstrated the presence of
      multinucleated myotubes expressing human muscle-specific markers. Our results
      suggest that PLC sponges loaded with myoblasts can be used for skeletal muscle
      engineering or for inducing muscle repair.

PMID- 23143920
TI  - Hydrogen peroxide and ecdysone in the cryoprotective dehydration strategy of
      Megaphorura arctica (Onychiuridae: Collembola).
AB  - The Arctic springtail, Megaphorura arctica, survives sub-zero temperatures in a
      dehydrated state via trehalose-dependent cryoprotective dehydration. Regulation
      of trehalose biosynthesis is complex; based in part on studies in yeast and
      fungi, its connection with oxidative stress caused by exposure of cells to
      oxidants, such as hydrogen peroxide (H2O2), or dehydration, is well documented.
      In this respect, we measured the amount of H2O2 and antioxidant enzyme activities
      (superoxide dismutases: copper, zinc--CuZnSOD and manganese containing--MnSOD,
      and catalase--CAT), as the regulatory components determining H2O2 concentrations,
      in Arctic springtails incubated at 5  degrees C (control) versus -2  degrees C
      (threshold temperature for trehalose biosynthesis). Because ecdysone also
      stimulates trehalose production in insects and regulates the expression of genes
      involved in redox homeostasis and antioxidant protection in Drosophila, we
      measured the levels of the active physiological form of ecdysone--20
      hydroxyecdysone (20-HE). Significantly elevated H2O2 and 20-HE levels were
      observed in M. arctica incubated at -2  degrees C, supporting a link between
      ecdysone, H2O2, and trehalose levels during cryoprotective dehydration. CAT
      activity was found to be significantly lower in M. arctica incubated at -2 
      degrees C versus 5  degrees C, suggesting reduced H2O2 breakdown. Furthermore,
      measurement of the free radical composition in Arctic springtails incubated at 5 
      degrees C (controls) versus -2  degrees C by Electron Paramagnetic Resonance
      spectroscopy revealed melanin-derived free radicals at -2  degrees C, perhaps an
      additional source of H2O2. Our results suggest that H2O2 and ecdysone play
      important roles in the cryoprotective dehydration process in M. arctica, linked
      with the regulation of trehalose biosynthesis.

PMID- 23143921
TI  - In vitro experiments with primary mammalian cells: to pool or not to pool?

PMID- 23143923
TI  - Opinion editorials: the science and art of combining evidence with opinion.
AB  - In the policy environment, the news media play a powerful and influential role,
      determining not only what issues are on the broad policy agenda, but also how the
      public and politicians perceive these issues. Ensuring that reporters and editors
      have access to information, that is, credible and evidence-based is critical for
      stimulating healthy public discourse and constructive political debates.
      EvidenceNetwork.ca is a non-partisan web-based project that makes the latest
      evidence on controversial health-policy issues available to the Canadian news
      media. This article introduces EvidenceNetwork.ca, the benefits it offers to
      journalists and researchers, and the important niche it occupies in working with
      the news media to build a more productive dialogue around healthcare. 

PMID- 23143924
TI  - Propargyl hydrazides: synthesis and conversion into pyrazoles through
      hydroamination.
AB  - Pyrazoles direct: propargyl alcohols undergo hydrazination when treated with p
      tosyl hydrazide in the presence of catalytic amounts of either Sc(OTf)(3) or
      La(OTf)(3) (see scheme; Tf=trifluoromethanesulfonyl). Propargyl hydrazides are
      converted into either N-tosyl or N-H pyrazoles when treated with an acid or a
      base, respectively. The one-step acid-catalyzed hydrazination/cyclization of
      propargyl alcohols directly affords pyrazoles in high yields.

PMID- 23143922
TI  - The influence of NaIO(3)-induced retinal degeneration on intra-retinal layer and
      the changes of expression profile/morphology of DA-ACs and mRGCS.
AB  - Sodium iodate (NaIO(3))-induced retina injury is one of models that is commonly
      used to study various retinal diseases caused by retinal pigment epithelium (RPE)
      injury such as AMD. Previous researches have revealed that RPE and photoreceptors
      are main impaired objects in this model. By comparison, intra-retinal layer has
      not been studied in detail after NaIO(3) administration. In this study, we
      present evidences that intra-retinal neurons can be directly injured by NaIO(3)
      at early stage and that the morphology had taken obvious changes, the decreased
      areas of dendritic fields of dopaminergic amacrine cells (DA-ACs), horizontal
      cells, and melanopsin-expressing retinal ganglion cells (mRGCs). Moreover, we
      found that miRNA 133b that was considered specifically to express in midbrain
      dopaminergic neurons was markedly upregulated in retinal DA-ACs after NaIO(3)
      administration. The overexpression of mir-133b negatively regulated the
      expression of pitx3, an important transcription factor, and led to a series of
      deficits of DA-ACs such as TH and D2 receptor expression and DA producing, which
      may play a causative role in pathological events of horizontal cells and mRGCs.
      After mir-133b was interfered with mir-133b/RNAi, not only those deficits were
      rescued, but also the amplitude of b-wave and summed OPs of ERG were improved
      significantly. In conclusion, our data demonstrate, for the first time, that
      intra-retinal neurons can be directly injured by NaIO(3) at early stage, and that
      mir-133b level effectively controls synaptic contacts or neural interactions
      among DA-ACs, horizontal cells, and mRGCs. Delivering mir-133b/RNAi
      intravitreally can rescue NaIO(3)-induced failure and improve visual function by
      restoring synaptic contacts.

PMID- 23143925
TI  - A species difference in the peroxisome proliferator-activated receptor alpha
      dependent response to the developmental effects of perfluorooctanoic acid.
AB  - This study examined the effect of prenatal perfluorooctanoic acid (PFOA)
      administration on pre- and postnatal development using peroxisome proliferator
      activated receptor alpha (PPARalpha)-humanized mice to determine if species
      differences in receptor activity might influence the developmental effects
      induced by PFOA. Pregnant mice were treated daily with water or PFOA (3mg/kg) by
      po gavage from gestation day 1 (GD1) until GD17 and then either euthanized on
      GD18 or allowed to give birth and then euthanized on postnatal day 20 (PND20). No
      changes in average fetal weight, crown-to-rump length, or placental weight were
      observed on GD18. Expression of mRNA encoding the PPARalpha target genes acyl CoA
      oxidase (Acox1) and cytochrome P450 4a10 (Cyp4a10) in maternal and fetal liver
      was increased on GD18 in wild-type and PPARalpha-humanized mice but not in
      Pparalpha-null mice. On PND20, relative liver weight was higher in wild-type mice
      but not in Pparalpha-null mice or PPARalpha-humanized mice. Hepatic expression of
      Acox1 and Cyp4a10 mRNA was higher in wild-type mice but not in Pparalpha-null
      mice or PPARalpha-humanized mice on PND20. The percentage of mice surviving
      postnatally was lower in wild-type litters but not in litters from Pparalpha-null
      mice or PPARalpha-humanized mice. No changes in pup weight gain, onset of eye
      opening, or mammary gland development were found in any genotype. Results from
      these studies demonstrate that the developmental/postnatal effects resulting from
      prenatal PFOA exposure in mice are differentially mediated by mouse and human
      PPARalpha.

PMID- 23143926
TI  - In vitro exposure of precision-cut lung slices to 2-(4-amino-3-methylphenyl)-5
      fluorobenzothiazole lysylamide dihydrochloride (NSC 710305, Phortress) increases
      inflammatory cytokine content and tissue damage.
AB  - The anticancer drug (2-[4-amino-3-methylphenyl]-5-fluorobenzothiazole lysylamide
      dihydrochloride) (NSC 710305, Phortress) is a metabolically activated prodrug
      that causes DNA adduct formation and subsequent toxicity. Preclinically, it was
      found that hepatic, bone marrow, and pulmonary toxicity presented challenges to
      developing this drug. An ex vivo precision-cut lung slice (PCLS) model was used
      to search for concentration dependent effects of NSC 710305 (10, 25, 50, and 100
      uM) on cytokine content, protein content, and immuno/histological endpoints.
      Preparation and culture of PCLS caused an initial spike in proinflammatory
      cytokine expression and therefore treatment with NSC 710305 was delayed until 48
      h after initiating the slice cultures to avoid confounding the response to
      slicing with any drug response. PCLSs were evaluated after 24, 48, and 72 h
      exposures to NSC 710305. Reversibility of toxicity due to the 72-h treatment was
      evaluated after a 24-h recovery period. NSC 710305 caused a concentration
      dependent cytokine response, and only the toxicity caused by a 72-h exposure to
      25 uM reversed during the 24-h recovery period. Immuno/histological examination
      and quantitation of tissue protein levels indicated that tissue destruction, ED-1
      (activated macrophage) staining, and protein levels were associated with the
      levels of proinflammatory cytokines in the tissue. In conclusion, the
      concentration- and time-dependent inflammatory response of PCLS to NSC 710305
      preceded relevant tissue damage by a few days. The no-observable adverse effect
      level (NOAEL) for 24, 48, and 72 h exposures was established as 10 uM NSC 710305.

PMID- 23143927
TI  - Application of an updated physiologically based pharmacokinetic model for
      chloroform to evaluate CYP2E1-mediated renal toxicity in rats and mice.
AB  - Physiologically based pharmacokinetic (PBPK) models are tools for interpreting
      toxicological data and extrapolating observations across species and route of
      exposure. Chloroform (CHCl(3)) is a chemical for which there are PBPK models
      available in different species and multiple sites of toxicity. Because chloroform
      induces toxic effects in the liver and kidneys via production of reactive
      metabolites, proper characterization of metabolism in these tissues is essential
      for risk assessment. Although hepatic metabolism of chloroform is adequately
      described by these models, there is higher uncertainty for renal metabolism due
      to a lack of species-specific data and direct measurements of renal metabolism.
      Furthermore, models typically fail to account for regional differences in
      metabolic capacity within the kidney. Mischaracterization of renal metabolism may
      have a negligible effect on systemic chloroform levels, but it is anticipated to
      have a significant impact on the estimated site-specific production of reactive
      metabolites. In this article, rate parameters for chloroform metabolism in the
      kidney are revised for rats, mice, and humans. New in vitro data were collected
      in mice and humans for this purpose and are presented here. The revised PBPK
      model is used to interpret data of chloroform-induced kidney toxicity in rats and
      mice exposed via inhalation and drinking water. Benchmark dose (BMD) modeling is
      used to characterize the dose-response relationship of kidney toxicity markers as
      a function of PBPK-derived internal kidney dose. Applying the PBPK model, it was
      also possible to characterize the dose response for a recent data set of rats
      exposed via multiple routes simultaneously. Consistent BMD modeling results were
      observed regardless of species or route of exposure.

PMID- 23143928
TI  - Novel insights into phosgene-induced acute lung injury in rats: role of
      dysregulated cardiopulmonary reflexes and nitric oxide in lung edema
      pathogenesis.
AB  - Phosgene gas is a lower respiratory tract irritant. As such, it stimulates
      nociceptive vagal C-fiber-related reflexes in a dose-rate and concentration *
      exposure duration (C * t)-dependent manner. In rats, this reflex is characterized
      by extended apnea time periods, bradycardia, and hypothermia. Although inhalation
      exposures at nonlethal C * t products show rapid reversibility of reflexively
      induced changes in respiratory patterns, lethal C * t products seem to cause
      prolonged stimulation after discontinued exposure to phosgene. This observation
      has been taken as indirect evidence that phosgene-induced lethal lung edema is
      likely to be associated with a dysfunctional neurogenic control of
      cardiopulmonary and microvascular physiology. In order to verify this hypothesis,
      data from respiratory function measurements during and after the inhalation
      exposure to phosgene gas were compared with time-course measurements of cardiac
      function over 20 h post-phosgene exposure. These data were complemented by time
      course analyses of nitric oxide (NO(e)) and carbon dioxide in exhaled breath,
      including time-dependent changes of extravasated protein in bronchoalveolar
      lavage fluid and hemoglobin in blood. The nitric oxidase synthetase inhibitors L
      NAME and L-NIL were used to further elucidate the role of NO(e) in this type of
      acute lung injury and whether its analysis can serve as an early biomarker of
      pulmonary injury. Collectively, the sequence and time course of pathological
      events in phosgene-induced lung edema appear to suggest that overstimulated,
      continued sensorimotor vagal reflexes affect cardiopulmonary hemodynamics. A
      continued parasympathetic tone appears to be involved in this etiopathology.

PMID- 23143929
TI  - Copper-promoted trifluoromethylation of primary and secondary alkylboronic acids.
AB  - New couple: The Cu-promoted trifluoromethylation of primary and secondary
      alkylboronic acids with TMSCF(3) extends the scope of transition-metal-catalyzed
      trifluoromethylation reactions to sp(3)-hybridized carbon centers. It also
      represents one of the first examples for Cu-catalyzed C-C cross-coupling
      reactions of alkylboronic acid derivatives.

PMID- 23143930
TI  - IsoDGR-tagged albumin: a new alphavbeta3 selective carrier for nanodrug delivery
      to tumors.
AB  - A new cyclic peptide containing the isoDGR motif that, after coupling to albumin,
      selectively binds alphavbeta3, an integrin overexpressed in the tumor
      vasculature. IsoDGR-tagged albumin binds tumor vessels and can be exploited as a
      carrier for the preparation of tumor vasculature-selective nanomedicines, such as
      gold nanoparticles (Au) carrying tumor necrosis factor alpha (TNF), a potent
      vascular damaging agent.

PMID- 23143931
TI  - Effect of airline travel on performance: a review of the literature.
AB  - The need for athletes to travel long distances has spurred investigation into the
      effect of air travel across multiple time zones on athletic performance. Rapid
      eastward or westward travel may negatively affect the body in many ways;
      therefore, strategies should be employed to minimise these effects which may
      hamper athletic performance. In this review, the fundamentals of circadian rhythm
      disruption are examined along with additional effects of airline travel including
      jet lag, sleep deprivation, travel at altitude and nutritional considerations
      that negatively affect performance. Evidence-based recommendations are provided
      at the end of the manuscript to minimise the effects of airline travel on
      performance.

PMID- 23143932
TI  - Improving the fermentation performance of Saccharomyces cerevisiae by laccase
      during ethanol production from steam-exploded wheat straw at high-substrate
      loadings.
AB  - Operating the saccharification and fermentation processes at high-substrate
      loadings is a key factor for making ethanol production from lignocellulosic
      biomass economically viable. However, increasing the substrate loading presents
      some disadvantages, including a higher concentration of inhibitors (furan
      derivatives, weak acids, and phenolic compounds) in the media, which negatively
      affect the fermentation performance. One strategy to eliminate soluble inhibitors
      is filtering and washing the pretreated material. In this study, it was observed
      that even if the material was previously washed, inhibitory compounds were
      released during the enzymatic hydrolysis step. Laccase enzymatic treatment was
      evaluated as a method to reduce these inhibitory effects. The laccase efficiency
      was analyzed in a presaccharification and simultaneous saccharification and
      fermentation process at high-substrate loadings. Water-insoluble solids fraction
      from steam-exploded wheat straw was used as substrate and Saccharomyces
      cerevisiae as fermenting microorganism. Laccase supplementation reduced strongly
      the phenolic content in the media, without affecting weak acids and furan
      derivatives. This strategy resulted in an improved yeast performance during
      simultaneous saccharification and fermentation process, increasing significantly
      ethanol productivity.

PMID- 23143933
TI  - Head injury and Parkinson's disease: a population-based study.
AB  - BACKGROUND: The epidemiological evidence on head injury and the risk of
      Parkinson's disease (PD) has been inconsistent. METHODS: We examined the relation
      between previous hospitalization for head injury and PD using a population-based
      nested case-control design based on the Swedish National Patient Register from
      2001 until 2007, including 18,648 PD cases and 93,240 controls, randomly selected
      from the general population. Exposure was defined as hospitalization for head
      injury between 1987 and index date. RESULTS: Overall, previous hospitalization
      resulting from head injury was associated with an increased risk of PD; this
      association appeared to be largely explained by head injuries experienced
      recently, especially within 1 year before PD ascertainment. CONCLUSIONS: Our
      results do not provide convincing evidence for a causal relationship between head
      injury later in life and PD.

PMID- 23143934
TI  - Does copper stress lead to spindle misposition-dependent cell cycle arrest?
AB  - Because of its specific electrochemical  properties, copper is an essential heavy
      metal for living organisms. As with  other heavy metals, high levels can provoke
      damage. We examined gene expression  under copper stress in wild-type fission
      yeast (Schizosaccharomyces  pombe) through differential display. After the EC(50)
      concentration of CuSO(4) was determined as 50 MUM, total RNA was isolated from
      cells  treated or not with copper. The expression level of SPCC1682.13, ppk1, 
      SPBC2F12.05c, and adg2 genes increased significantly under copper stress. 
      Considering the functions of these genes are related to the cell cycle, cell 
      division and chromosome dynamics, we hypothesize that retardation of the cell 
      cycle under copper stress is relevant to the events that depend on the  functions
      of these genes.

PMID- 23143935
TI  - Reevaluation of RAPD markers  involved in a case of stingray misidentification
      (Dasyatidae: Dasyatis).
AB  - We  investigated a reported case of stingray Dasyatis americana misidentification
      not detected in a published study using the random amplified polymorphic DNA 
      (RAPD) technique. If the referred specimen (landed by fisheries in Ceara, 
      northeastern Brazil) was misidentified (as Dasyatis centroura) in the  field, why
      did its RAPD data fail to clarify the mistake? Was it due to limitations  of RAPD
      markers or perhaps to a taxonomic issue? Contrary to our initial  expectations,
      neither of these hindered the detection of the misidentification.  After
      reanalyzing the primary genetic data associated with the misidentified  specimen
      (PCR gel photographs and/or matrices of presence/absence of markers  for six RAPD
      primers), we found that the RAPD markers were sufficient to  correctly assign the
      misidentified specimen to its proper species identity. In  the original study,
      the specimen misidentification was neither noticed by the  authors nor apparent
      in the published article due to how their results were  interpreted and
      presented.

PMID- 23143936
TI  - A selective palladium-catalyzed carbonylative arylation of aryl ketones to give
      vinylbenzoate compounds.
AB  - Preparation of enols: when treated with [{Pd(cinnamyl)Cl}(2)]/cataCXium A
      (nBuPAd(2), Ad=adamantyl) under an atmosphere of CO, aryl ketones react with aryl
      halides in a carbonylative C-O coupling reaction to form (Z)-vinyl benzoates.

PMID- 23143937
TI  - Diazonium functionalized graphene: microstructure, electric, and magnetic
      properties.
AB  - The unique honeycomb lattice structure of graphene gives rise to its outstanding
      electronic properties such as ultrahigh carrier mobility, ballistic transport,
      and more. However, a crucial obstacle to its use in the electronics industry is
      its lack of an energy bandgap. A covalent chemistry strategy could overcome this
      problem, and would have the benefits of being highly controllable and stable in
      the ambient environment. One possible approach is aryl diazonium
      functionalization.  In this Account, we investigate the micromolecular/lattice
      structure, electronic structure, and electron-transport properties of nitrophenyl
      diazonium-functionalized graphene. We find that nitrophenyl groups mainly adopt
      random and inhomogeneous configurations on the graphene basal plane, and that
      their bonding with graphene carbon atoms leads to slight elongation of the
      graphene lattice spacing. By contrast, hydrogenated graphene has a compressed
      lattice. Low levels of functionalization suppressed the electric conductivity of
      the resulting functionalized graphene, while highly functionalized graphene
      showed the opposite effect. This difference arises from the competition between
      the charge transfer effect and the scattering enhancement effect introduced by
      nitrophenyl groups bonding with graphene carbon atoms. Detailed electron
      transport measurements revealed that the nitrophenyl diazonium functionalization
      locally breaks the symmetry of graphene lattice, which leads to an increase in
      the density of state near the Fermi level, thus increasing the carrier density.
      On the other hand, the bonded nitrophenyl groups act as scattering centers,
      lowering the mean free path of the charge carriers and suppressing the carrier
      mobility.  In rare cases, we observed ordered configurations of nitrophenyl
      groups in local domains on graphene flakes due to fluctuations in the reaction
      processes. We describe one example of such a superlattice, with a lattice
      constant nearly twice of that of pristine graphene. We performed comprehensive
      theoretical calculations to investigate the lattice and the electronic structure
      of the superlattice structure. Our results reveal that it is a thermodynamically
      stable, spin-polarized semiconductor with a bandgap of ~0.5 eV.  Our results
      demonstrate the possibility of controlling graphene's electronic properties using
      aryl diazonium functionalization. Asymmetric addition of aryl groups to different
      sublattices of graphene is a promising approach for producing ferromagnetic,
      semiconductive graphene, which will have broad applications in the electronic
      industry.

PMID- 23143938
TI  - Electrodeposition of crystalline and photoactive silicon directly from silicon
      dioxide nanoparticles in molten CaCl2.

PMID- 23143939
TI  - Comparison of intranasal ketorolac tromethamine pharmacokinetics in younger and
      older adults.
AB  - BACKGROUND: The nonsteroidal anti-inflammatory drug (NSAID) ketorolac
      tromethamine shows higher plasma concentrations and a longer plasma half-life in
      adults >=65 years of age than in subjects aged <65 years, after intramuscular
      administration. An intranasal formulation of ketorolac tromethamine is approved
      for short-term treatment of moderate to moderately severe pain requiring
      analgesia at the opioid level. OBJECTIVE: The objective of this study was to
      compare the pharmacokinetics of a single intranasal dose of ketorolac
      tromethamine 31.5 mg (15.75 mg per nostril) in adults aged >=65 and <65 years.
      METHODS: Healthy adults with body mass indices of 15-30 kg/m(2) were eligible for
      the study. Following intranasal ketorolac tromethamine dosing, blood samples
      (approximately 7 mL per sample) for pharmacokinetic assessment were obtained at
      15, 30 and 45 min and 1, 1.5, 2, 4, 6, 8, 12, 15 and 24 h after dosing. Plasma
      ketorolac concentration versus time data were analysed to determine maximum
      (peak) ketorolac concentration (C(max)) and time to reach C(max) (t(max)) and
      estimate pharmacokinetic parameters. RESULTS: Thirty healthy subjects were
      enrolled in and completed the study. For analysis, data were stratified by
      participant age into two groups, consisting of younger adult subjects (<65 years
      of age) and older adult subjects (>=65 years of age). Mean (+/-SD) age was 44 +/-
      10 and 72 +/- 6 years in the younger and older groups, respectively. Mean (+/-SD)
      plasma ketorolac C(max) was 10 % higher (2,028.8 +/- 1,069.5 and 1,840.1 +/-
      995.9 ng/mL) and mean (+/-SD) terminal elimination half-life (t(1/2beta)) was 37
      % longer (4.52 +/- 1.14 and 3.31 +/- 0.96 h) in the >=65-years age group than in
      the <65-years group, respectively. Mean (+/-SD) plasma ketorolac area under the
      plasma concentration-time curve from time zero to infinity (AUC(infinity)) was 28
      % higher in older subjects than in younger subjects (8,794.8 +/- 4,129.4 and
      6,890.8 +/- 3,448.5 ng . h/mL, respectively). Differences were not statistically
      significant, but did not demonstrate formal equivalence. Mean (+/-SD) residence
      time was 36 % higher in the >=65-years age group than in the <65-years group
      (6.02 +/- 1.50 and 4.44 +/- 1.06 h, respectively) (p = 0.003). There were no
      serious adverse events during the study. Two mild events of headache and eyelid
      infection occurred. There were no clinically relevant changes or an apparent
      difference between age groups in laboratory or physical assessments. CONCLUSION:
      The increased systemic exposure to ketorolac following intranasal administration
      in adults >=65 years of age warrants reduction of the intranasal ketorolac
      tromethamine dose, and halving the dose to 15.75 mg (one spray to one nostril) in
      this patient population is recommended based on similar dosing adjustments made
      for intramuscular ketorolac tromethamine.

PMID- 23143940
TI  - Treatment of chronic pain in older people: evidence-based choice of strong-acting
      opioids.

PMID- 23143942
TI  - An electronic system to document reasons for medication discontinuation and to
      flag unwanted represcriptions in geriatric patients.
AB  - BACKGROUND: Earlier studies have shown poor documentation of the reasons for
      medication discontinuation during hospitalization. Communication of reasons for
      discontinuation, e.g. adverse drug reactions (ADRs), to general practitioners and
      pharmacists was also found to be insufficient, leading to a rate of
      represcription after an ADR of 27% during the first 6 months after discharge.
      OBJECTIVE: The aim of this study was to develop and implement a user-friendly
      electronic clinical decision support system to document reasons for medication
      discontinuation in hospitalized geriatric patients and to flag potentially
      undesirable represcriptions. METHODS: The electronic clinical decision support
      module was developed using the Gaston framework. Pop-up windows force physicians
      to document reasons for medication discontinuation, and the system alerts
      physicians to the represcription of drugs withdrawn because of an ADR. We
      interviewed users regarding the acceptability of the system. RESULTS: On a 20-bed
      geriatric ward, the electronic system documented 2,228 medication
      discontinuations and the reasons for them over 11.4 months and alerted physicians
      to represcription of drugs associated with an ADR 20 times. The system was
      considered to be user-friendly. CONCLUSIONS: This clinical decision support
      system fulfilled its aims of documenting the reasons for medication
      discontinuation and alerting physicians to potentially undesirable represcription
      of previously withdrawn drugs. It was found to be user-friendly.

PMID- 23143943
TI  - Children of migrant parents may be at greater risk of low-functioning autism
      spectrum disorder, but lower risk of high-functioning autism spectrum disorder.

PMID- 23143944
TI  - Three dimensional, sheathless, and high-throughput microparticle inertial
      focusing through geometry-induced secondary flows.
AB  - A novel inertial focusing platform creates a single-stream microparticle train in
      a single-focal plane without sheath fluids and external forces, all in a high
      throughput manner. The proposed design consists of a low-aspect-ratio straight
      channel interspersed with a series of constrictions in height arranged
      orthogonally, making use of inertial focusing and geometry-induced secondary
      flows. Focusing efficiency as high as 99.77% is demonstrated with throughput as
      high as 36 000 particles s(-1) for a variety of different sized particles and
      cells.

PMID- 23143945
TI  - Nutritional attributes of ash (Fraxinus spp.) outer bark and phloem and their
      relationships to resistance against the emerald ash borer.
AB  - The emerald ash borer (Agrilus planipennis Fairmaire, EAB) is an alien, invasive
      wood-boring insect that is responsible for killing millions of ash trees since
      its discovery in North America in 2002. All North American ash species (Fraxinus
      spp.) that EAB has encountered have shown various degrees of susceptibility,
      while Manchurian ash (Fraxinus mandshurica Ruprecht), which shares a co
      evolutionary history with this insect, is resistant. Recent studies have looked
      into constitutive resistance mechanisms in Manchurian ash, concentrating on the
      secondary phloem, which is the feeding substrate for the insect. In addition to
      specialized metabolism and defense-related components, primary metabolites and
      nutritional summaries can also be important to understand the feeding behavior of
      insect herbivores. Here, we have compared the nutritional characteristics (water
      content, total protein, free amino acids, total soluble sugars and starch,
      percent carbon and nitrogen, and macro- and micronutrients) of outer bark and
      phloem from black, green, white and Manchurian ash to determine their relevance
      to resistance or susceptibility to EAB. Water content and concentrations of Al,
      Ba, Cu, Fe, K, Li, tryptophan and an unknown compound were found to separate
      black and Manchurian ash from green and white ash in a principal component
      analysis (PCA), confirming their phylogenetic placements into two distinct
      clades. The traits that distinguished Manchurian ash from black ash in the PCA
      were water content and concentrations of total soluble sugars, histidine, lysine,
      methionine, ornithine, proline, sarcosine, tyramine, tyrosol, Al, Fe, K, Na, V
      and an unknown compound. However, only proline, tyramine and tyrosol were
      significantly different, and higher, in Manchurian ash than in black ash.

PMID- 23143946
TI  - Specific genetic polymorphisms of IL10-592 AA and IL10-819 TT genotypes lead to
      the key role for inducing docetaxel-induced liver injury in breast cancer
      patients.
AB  - AIM: This study was designed to explore the genetic polymorphism of IL-10 (
      1082A/G, -592A/C, -819T/C), TNF-alpha (-308G/A) with susceptibility to docetaxel
      induced liver injury (DILI) in Chinese breast cancer patients. METHODS: The
      targeted genetic polymorphisms of IL10-1082G/A, IL10-592A/C, IL10-819T/C, TNF
      308G/A from 40 patients with DILI were assayed by matrix-assisted laser
      desorption/ionization-time of flight of Sequenom. RESULTS: AA genotype of IL10
      592 and TT of IL10-819 significantly increased incidence of DILI (P = 0.005, OR =
      3.137). No differences of TNF gene polymorphism between the two groups were seen.
      CONCLUSION: The genetic polymorphism of the IL10-592A/C AA genotype and IL10
      819T/C TT genotype was predominantly conferred to the incidence of docetaxel
      induced liver injury.

PMID- 23143947
TI  - Clinical and mutation analysis of four Chinese families with von Hippel-Lindau
      disease.
AB  - OBJECTIVE: von Hippel-Lindau (VHL) disease is a hereditary tumor syndrome
      predisposed to the development of tumors in a variety of body organs. The major
      etiopathogenesis of VHL is a mutation of the VHL tumor-suppressor gene on the
      short arm of chromosome 3 (3p25-26). We report on the clinical and molecular
      features of four Chinese kindreds with VHL disease. MATERIALS AND METHODS: The
      VHL gene was screened for mutation using a direct DNA sequencing analysis and a
      multiplex ligation-dependent probe amplification (MLPA) for 44 volunteers from
      these four families. Any unaffected person, with germline VHL gene mutation, was
      required to undergo further examination, surveillance and treatment. RESULTS: The
      main lesions and the average diagnostic year of the 20 patients were central
      nervous system hemangioblastoma (60 %, 34.92 years), renal lesion (60 %, 39.08
      years), pancreatic lesion (60 %, 37.67 years), adrenal pheochromocytoma (25 %,
      37.8 years) and retinal hemangioblastoma (10 %, 25.5 years). Direct sequencing
      detected nucleotide substitutions or small deletions in three families and MLPA
      revealed exon 1 deletion in family A. The five asymptomatic patients were
      initially diagnosed by genetic analysis and verified radiologically or
      surgically. CONCLUSIONS: The spectrum of clinical manifestation of VHL in the
      mainland Chinese population is similar to the observation in Western kindreds.
      Genetic testing, which plays a crucial role in early diagnosis asymptomatic
      patients, is obviously superior to clinical informations when diagnosing VHL
      disease. The members of VHL disease family may benefit from pedigree study,
      genetic testing, periodic follow-up, early diagnosis and prompt treatment.

PMID- 23143948
TI  - Intraoperative radiotherapy for the treatment of resectable locally advanced
      gastric adenocarcinoma: topography of locoregional recurrences and long-term
      outcomes.
AB  - INTRODUCTION: To report feasibility, tolerance, anatomical sites of upper
      abdominal locoregional recurrence and long-term outcome of gastric cancer
      patients treated with surgery and a component of intraoperative electron beam
      radiotherapy (IORT). MATERIALS AND METHODS: From January 1995 to December 2010,
      32 patients with primary gastric adenocarcinoma treated with curative resection
      (R0) [total gastrectomy (n = 9; 28 %), subtotal (n = 23; 72 %) and D2
      lymphadenectomy in all patients] and apparent disease confined to locoregional
      area [Stage: II (n = 15; 47 %), III (n = 17; 53 %)] were treated with a component
      of IORT (IORT applicator size 5-9 cm in diameter, dose 10-15 Gy, beam energy 6-5
      MeV) over the celiac axis and peripancreatic nodal areas. Sixteen (50 %) patients
      also received adjuvant treatment (external beam radiotherapy n = 6,
      chemoradiation n = 9, chemotherapy alone n = 1). RESULTS: With a median follow-up
      time of 40 months (range, 2-60), locoregional recurrence was observed in five (16
      %) patients (4 nodal in hepatic hilum and 1 anastomotic). Only pN1 patients
      developed locoregional relapse. No recurrence was observed in the IORT-treated
      target volume (celiac trunk and peripancreatic nodes). Overall survival at 5
      years was 54.6 % (95 % CI: 48.57-60.58). Postoperative mortality was 6 % (n = 2)
      and postoperative complications 19 % (n = 6). CONCLUSIONS: It is feasible to
      integrate IORT as a component of radiotherapy in combined modality therapy of
      gastric cancer. Local control is high in the radiation boosted area, but marginal
      regional extension (in particular, involving the hepatic hilum) might be
      considered as part of the anatomic IORT target volume at risk in pN+ patients.

PMID- 23143949
TI  - Pilot study of feasibility and dosimetric comparison of prone versus supine
      breast radiotherapy.
AB  - PURPOSE: The aim of this study was to demonstrate feasibility and analyze
      dosimetric differences in prone and supine position breast cancer radiotherapy in
      women with large or pendulous breast. METHODS: Ten post-lumpectomy breast cancer
      patients underwent supine and prone computed tomography-based treatment plan. On
      each data set, the whole breast, the ipsilateral lung and the heart were
      outlined. Multisegment tangential-fields plans were generated for each position.
      Target coverage, homogeneity, overdosage outside breast and organ at risk sparing
      were analyzed and compared for supine and prone position. RESULTS: Coverage and
      dose homogeneity of the PTV measured by D 90 and V(95)% were similar for both
      plans although breast maximum dose was higher in the supine plan (p = 0.017).
      Prone position reduced the percentage of ipsilateral lung receiving 20 Gy
      (V(20Gy)) from 26.5 to 2.9 % (p = 0.007), medium lung dose, as well as the
      percentage of the heart receiving 35 Gy heart (V(35Gy)) from 3.4 to 1.2 % (p =
      0.038). Overdosage of areas outside breast PTV was also consistently reduced with
      prone position (p = 0.012). In addition, average number of segments and monitor
      units needed was reduced in prone position. CONCLUSIONS: Prone position in large
      breast women appears to favor normal tissue sparing in breast radiotherapy as
      compared to supine position, without diminishing the target coverage.

PMID- 23143950
TI  - Viruses in cancer treatment.
AB  - Soon after the discovery that viruses cause human disease, started the idea of
      using viruses to treat cancer. After the initial indiscriminate use, crude
      preparations of each novel virus in the early twentieth century, a second wave of
      virotherapy blossomed in the 60s with purified and selected viruses. Responses
      were rare and short-lived. Immune rejection of the oncolytic viruses was
      identified as the major problem and virotherapy was abandoned. During the past
      two decades virotherapy has re-emerged with engineered viruses, with a trend
      towards using them as tumor-debulking immunostimulatory agents combined with
      radio or chemotherapy. Currently, oncolytic Reovirus, Herpes, and Vaccinia virus
      are in late phase clinical trials. Despite the renewed hope, efficacy will
      require improving systemic tumor targeting, overcoming stroma barriers for virus
      spread, and selectively stimulating immune responses against tumor antigens but
      not against the virus. Virotherapy history, viruses, considerations for clinical
      trials, and hurdles are briefly overviewed.

PMID- 23143951
TI  - Preoperative treatment with bevacizumab in combination with chemotherapy in
      patients with unresectable metastatic colorectal carcinoma.
AB  - PURPOSE: This prospective observational study assessed the efficacy of
      bevacizumab in combination with chemotherapy as preoperative treatment to
      downsize tumours for radical resection in patients with unresectable metastatic
      colorectal cancer (mCRC). PATIENTS/METHODS: Patients with mCRC initially
      unresectable according to predefined criteria were included. Preoperative
      treatment consisted of bevacizumab (5 mg/kg) combined with oxaliplatin- or
      irinotecan-based chemotherapy, which was followed by surgery in patients showing
      clinical benefit. Resection rate was the primary endpoint. Response rate (RR) and
      clinical benefit of preoperative chemotherapy, and overall survival (OS) were
      secondary endpoints. RESULTS: A total of 120 eligible patients were included and
      received preoperative treatment. Chemotherapy was irinotecan-based in 73 (61 %)
      patients, oxaliplatin-based in 25 (21 %) and 22 (18 %) patients received more
      than one line. A RR of 30 % and a clinical benefit rate of 73 % were observed
      with preoperative chemotherapy. Metastatic resection was possible in 61 (51 %)
      patients. Median OS was 33 months (95 % CI 31-NA months) for patients undergoing
      surgery, and 15 months (95 % CI 11-25 months) in non-operated patients. Thirty
      five patients experienced 59 postoperative complications (morbidity rate 57 %).
      CONCLUSION: Preoperative bevacizumab-based chemotherapy offers a high surgical
      rescue rate in patients with initially unresectable mCRC.

PMID- 23143952
TI  - Is it necessary to dissect the lymph nodes around an abnormal hepatic artery in
      D2 lymphadenectomy for gastric cancer?
AB  - BACKGROUND: Surgical resection remains the principal treatment for advanced
      gastric cancer. However, one of the difficulties in radical D2 lymphadenectomy is
      the identification of the vascular abnormalities around the stomach, especially
      abnormal hepatic artery. The hepatic artery arising from the superior mesenteric
      artery shows great variations, and whether or not the lymphatic tissues around
      the abnormal artery should be dissected is still controversial. METHOD: Eighty
      six gastric cancer patients who underwent radical D2 lymphadenectomy by the same
      surgeon in our department in the past 2 years were included in this study. All
      patients underwent multislice spiral computed tomography angiography for
      preoperative evaluation of the abnormal hepatic artery arising from the superior
      mesenteric artery. Postoperative immunohistochemistry of the lymphoid tissues
      around the abnormal hepatic artery was performed using CK20 and CEA antibodies to
      determine the occurrence of lymph node micrometastasis around the abnormal
      artery. RESULTS: In our study, we found 14 cases with an abnormal hepatic artery
      arising from the superior mesenteric artery. The hepatic artery ran in front of
      the pancreas in 1 case and behind the pancreas in 13 cases. Immunohistochemical
      analyses revealed no micrometastasis in the lymphoid tissues surrounding the
      abnormal artery. CONCLUSIONS: Abnormal hepatic arteries arising from the superior
      mesenteric artery can be classified into pre-pancreas and post-pancreas types.
      Lymph nodes around the abnormal artery may not need to be dissected in radical D2
      lymphadenectomy.

PMID- 23143953
TI  - Stereotactic ablative radiotherapy delivered by image-guided helical tomotherapy
      for extracranial oligometastases.
AB  - PURPOSE: To investigate the outcomes and risk factors of patients treated with
      stereotactic ablative radiotherapy (SABR) delivered by image-guided helical
      tomotherapy (HT) for extracranial oligometastases. METHODS: From August 2006
      through July 2011, 42 consecutive patients (median age 69 years [range 16-87])
      with oligometastases (<=3) received HT to all known cancer sites (lung, n = 28;
      liver, n = 12; adrenal, n = 2). Prognostic factors were assessed by Cox's
      proportional hazards regression analysis. RESULTS: A total of 60 lesions were
      treated with hypofractionated HT (median dose 39 Gy [range 36-72.5]; median dose
      per fraction 12 Gy [range 5-20]). Complete or partial response was observed in 40
      (54 %) patients. With a median follow-up period of 15 months, 1- and 2-year
      overall survival (OS) was 84 and 63 %, respectively; and 1- and 2-year local
      control (LC) was 92 and 86 %, respectively. Four patients had pneumonitis Grade
      >=2 and two patients had lower gastrointestinal toxicity Grade >=2. Only the lack
      of complete/partial response was associated with higher risk of mortality on
      univariate (HR = 3.8, P = 0.04) and multivariate (HR = 6.6, P = 0.01) analyses.
      CONCLUSIONS: SABR delivered by image-guided HT is well tolerated and offers
      adequate LC with low acute morbidity in patients with extracranial
      oligometastatic disease. We found that the response to HT was the only predictor
      for OS.

PMID- 23143954
TI  - A novel peptide (Thx) homing to non-small cell lung cancer identified by ex vivo
      phage display.
AB  - AIM: To identify linear peptide homing to non-small cell lung cancer (NSCLC)
      tumor cells using ex vivo phage display method. MATERIALS AND METHODS: Twenty-six
      clinical patient samples were used to identify linear homing peptide, which was
      exposed to NSCLC cell cultures and control cell lines to determine cell binding
      affinity and cell localization. Also, ex vivo biodistribution was analyzed using
      tumor-bearing mice. RESULTS: The panning yielded peptide enrichment with a core
      motif (A)/SRXPXXX. Based on this, an amino acid sequence, ARRPKLD, was selected
      for characterization and named Thx-peptide. The in vitro binding properties of
      Thx-peptide demonstrated selectivity toward NSCLC. Internalization assays showed
      that Thx-Alexa and fluorescein conjugates were located in a subset of
      perinuclearly located lysosomes of tumor cells. Thx-peptide appeared with
      fluorescein-labeled peptide and peptide-DTPA-chelator complex in adenocarcinoma
      xenografts in mice. CONCLUSION: Thx shows promise for targeted imaging and drug
      delivery.

PMID- 23143955
TI  - Comparison of second-line treatment outcomes between sensitive and refractory
      small cell lung cancer patients: a retrospective analysis.
AB  - PURPOSE: Small cell lung cancer (SCLC) has a high relapse rate despite being very
      chemosensitive. The efficacy of second-line treatment is dismal. Our aim was to
      evaluate the outcome of second-line treatment. METHODS: We retrospectively
      assessed data of 120 SCLC patients who failed first-line treatment and received
      second-line treatment at three medical oncology centers. RESULTS: Median age of
      group was 58. 82 % had an ECOG PS of 0-1 at the time of relapse. 39 % were at
      limited stage (LS) at the time of diagnosis. Patients who progressed more than 3
      months after first-line therapy were categorized as having platinum-sensitive
      disease (PSD) (64 %). The number of patients who received platin-based
      combination treatment was 33 (27 %). The median OS time starting from the
      initiation of second-line treatment was 7 months. Multivariate analysis
      identified PS (p = 0.006), extent of disease at diagnosis (0.014) and PSD (0.001)
      as the independent prognostic factors for survival. Subgroup analyses of the
      patients with PSD indicated platin rechallenge yields higher progression-free
      survival, overall survival and overall response rate. CONCLUSION: Patients with
      good ECOG PS,who have PSD or initially presenting with LS, have a good prognosis
      and in patients with PSD, platinum-based therapy would be more appropriate.

PMID- 23143956
TI  - Increased expression of CD24 is associated with tumor progression and prognosis
      in patients suffering osteosarcoma.
AB  - OBJECTIVE: As a small heavily glycosylated mucin-like glycosyl
      phosphatidylinositol-anchored cell surface protein, CD24 plays an important role
      in carcinogenesis of various human malignancies. However, its involvement in
      osteosarcoma is still unclear. The aim of this study was to investigate the
      expression pattern and the clinical significance of CD24 in human osteosarcoma.
      METHODS: CD24 mRNA and protein expression levels were, respectively, detected by
      RT-PCR and Western blot assays using 30 pairs of osteosarcoma and noncancerous
      bone tissues. Then, immunohistochemistry was performed to analyze the association
      of CD24 expression in 166 osteosarcoma tissues with clinicopathological factors
      or survival of patients. RESULTS: CD24 expression at mRNA and protein levels were
      both significantly higher in osteosarcoma tissues than those in corresponding
      noncancerous bone tissues (both P < 0.001). In addition, CD24 protein was
      positively expressed in 129 of 166 (77.7 %) osteosarcoma specimens with a
      cytoplasmic and membraneous staining, and also increased in the osteosarcoma
      specimens with advanced clinical stage (P = 0.01) and positive distant metastasis
      (P = 0.005). The univariate and multivariate analyses showed that osteosarcoma
      patients with high CD24 expression had poorer overall and disease-free survival,
      and high CD24 expression was an independent prognostic factor for both overall
      and disease-free survival. CONCLUSION: The aforementioned findings offer
      convincing evidence for the first time that the increased expression of CD24 is
      correlated with tumor aggressiveness and tumor metastasis of osteosarcoma, and
      this molecule is an independent prognostic marker for osteosarcoma patients.

PMID- 23143957
TI  - Synthesis and structure-property relationships of 2,2'-bis(benzo[b]phosphole) and
      2,2'-benzo[b]phosphole-benzo[b]heterole hybrid pi systems.
AB  - The first comprehensive study of the synthesis and structure-property
      relationships of 2,2'-bis(benzo[b]phosphole)s and 2,2'-benzo[b]phosphole
      benzo[b]heterole hybrid pi systems is reported. 2-Bromobenzo[b]phosphole P-oxide
      underwent copper-assisted homocoupling (Ullmann coupling) and palladium-catalyzed
      cross-coupling (Stille coupling) to give new classes of benzo[b]phosphole
      derivatives. The benzo[b]phosphole-benzo[b]thiophene and -indole derivatives were
      further converted to P,X-bridged terphenylenes (X = S, N) by a palladium
      catalyzed oxidative cycloaddition reaction with 4-octyne through the C(beta)-H
      activation. X-ray analyses of three compounds showed that the benzo[b]phosphole
      benzo[b]heterole derivatives have coplanar pi planes as a result of the effective
      conjugation through inter-ring C-C bonds. The pi-pi* transition energies and
      redox potentials of the cis and trans isomers of bis(benzo[b]phosphole) P-oxide
      are very close to each other, suggesting that their optical and electrochemical
      properties are little affected by the relative stereochemistry at the two
      phosphorus atoms. The optical properties of the benzo[b]phosphole
      benzo[b]heterole hybrids are highly dependent on the benzo[b]heterole subunits.
      Steady-state UV/Vis absorption/fluorescence spectroscopy, fluorescence lifetime
      measurements, and theoretical calculations of the non-fused and acetylene-fused
      benzo[b]phosphole-benzo[b]heterole pi systems revealed that their emissive
      excited states consist of two different conformers in rapid equilibrium.

PMID- 23143958
TI  - [Initial situation and approach to the care of migraine in neurology services in
      Spain: the PRIMERA study].
AB  - INTRODUCTION: Despite the high degree of disability it entails, many patients
      with migraine have never visited their doctor for this reason. It is necessary to
      conduct a study to examine the characteristics of first-time visits as a step
      that must be carried out prior to establishing specific intervention measures for
      this group of patients. AIM: To determine the profile of the patients with
      migraine who visit a neurology service for the first time, together with the
      diagnostic and therapeutic attitudes that neurologists display towards them.
      PATIENTS AND METHODS: We conducted a cross-sectional, multi-centre study of
      neurology services across the country. The research included 168 neurologists who
      recruited 851 patients (74.6% females; mean age: 34.0 +/- 10.7 years). Disability
      was assessed by means of the specific migraine questionnaire (Headache Impact
      Test) and the generic disability questionnaire (Sheehan Disability Scale).
      RESULTS: A third (66.5%) of the patients went for consultation following their
      doctor's advice, while the remaining 33.5% went on their own accord. Only 55.9%
      had been previously diagnosed with migraine. The main reasons for visiting were
      ineffective symptomatic treatment (25%) and an increase in the frequency or
      intensity of the attacks (23.4%). Although 70.3% of the patients had high
      disability scores on the Headache Impact Test, only 17.4% used specific treatment
      and only 13.3% were on preventive treatment. CONCLUSIONS: The PRIMERA study
      confirms, once again, that migraine is an under-diagnosed and under-treated
      condition in our setting, which means that specific educational interventions and
      training are still required for this pathology.

PMID- 23143959
TI  - [Processing speed in relapsing-remitting multiple sclerosis: the role played by
      the depressive symptoms].
AB  - INTRODUCTION: Reduced speed of information processing seems to characterize
      neuropsychological performance in multiple sclerosis (MS) patients. However, the
      impact in speed of information processing of depressive symptoms, that are highly
      prevalent in this population, has not been precisely defined yet due to the
      presence of some methodological limitations in most preceding studies. SUBJECTS
      AND METHODS: 42 MS remittent recurrent patients, 20 with depressive symptoms (BDI
      > 13), and 22 without, were compared to 24 healthy controls in neuropsychological
      tasks of speed of processing (SDMT, Stroop, TMT y PASAT-BNB). RESULTS: MS
      patients without depressive symptoms performed significantly worse than healthy
      controls the Stroop (W, C and WC), and the PASAT-BNB (execution time) tests. MS
      patients with depressive symptoms performed significantly worse than healthy
      controls the Stroop (W, C and WC), SDMT, TMT (A, B and B-A), and the PASAT-BNB
      (execution time and errors) tests. MS patients with depressive symptoms performed
      significantly worse than MS patients without depressive symptoms the SDMT, TMT
      (A, B and B-A), and the PASAT-BNB (execution time) tests. CONCLUSIONS: MS impact
      was not generalized in neuropsychological performance of patients. Depressive
      symptoms seem to play and important role determining the speed deficit. While MS
      reduced speed of information processing, depressive symptoms were associated to
      specific cognitive deficit different from speed ones.

PMID- 23143960
TI  - [Anti-NMDA receptor encephalitis in a 3-year-old girl with no associated
      pathology involving a tumour].
AB  - INTRODUCTION: Encephalitis due to NMDA receptors antibodies is a relatively
      common condition but it was under diagnosed until recently. It courses
      predictably and similarly in adults and children, although there are some
      differences, still less its association with tumours. CASE REPORT: A 3 years-old
      girl who was admitted to our hospital with symptoms compatible with acute
      encephalitis, so we started treatment with acyclovir. During admission she was
      alterning periods of poor response to stimuli with periods of agitation, and
      progressed to complete silence, adding sleep problems. She suffered epileptic
      seizures, dystonic movements and autonomic disturbances. Cranial MRI showed mild
      cortical atrophy and EEG generalized slowing of base tracing. Repeated samples of
      cerebral spinal fluid were normal from cytological and biochemical point of view.
      In view of the torpid evolution she began methylprednisolone therapy and later
      inmunoglobulins with no improvement. Upon confirmation of the positivity for NMDA
      receptors antibodies in cerebral spinal fluid and serum, cyclophosphamide was
      administered, with gradual improvement of symptoms until full recovery. After ten
      months of follow-up without treatment she has not presented relapses and has
      ruled out the presence of tumours. CONCLUSIONS. It is important to recognize
      encephalitis with behavioural changes and abnormal movements, because early
      diagnosis and the beginning of appropriate therapy could improve the prognosis.

PMID- 23143961
TI  - [Psychological and behavioural symptoms of dementia: prevention, diagnosis and
      treatment].
AB  - INTRODUCTION: The psychological and behavioural symptoms of dementia (BPSD)
      [corrected] give rise to personal suffering, are the cause of added deterioration
      and worsen the economic and social cost of dementias. AIM: To offer a systematic
      approach to the prevention, diagnosis and treatment of BPSD. [corrected].
      DEVELOPMENT: The study adopts a global perspective that takes into account
      biological, psychological and social factors in an attempt to avoid both
      excessive medicalisation and a purely psychology-based attitude. Satisfying basic
      needs, treating medical and psychiatric comorbidity, the adaptation of the
      setting, and the specific pharmacological treatment of dementia, as well as
      offering patients and their caregivers the counselling and support they need, all
      contribute to prevent the onset of BPSD. [corrected]. The diagnosis of BPSD
      [corrected] is based on the patient's medical history and on observation. It is
      useful to identify a primary or destabilising BPSD [corrected] on which to deploy
      hypotheses and specific treatments based on modifying the environment, drugs, non
      pharmacological therapies and continuous assessment. Any action taken must be
      integrated within a person-focused care plan aimed at accomplishing the patients'
      and their caregivers' welfare and quality of life. CONCLUSIONS: BPSD [corrected]
      are the result of biological, psychological and social factors. In the present
      scenario, in which there are no curative treatments in most cases of dementia, a
      systematic and multidisciplinary approach aimed at preventing and treating BPSD
      [corrected] is a highly cost-effective therapeutic opportunity in both personal
      and social terms.

PMID- 23143962
TI  - [Genetic bases of attention deficit hyperactivity disorder].
AB  - AIMS: The purpose of this study is to update the information available on the
      main group of genes that have been related with a susceptibility to attention
      deficit hyperactivity disorder (ADHD) or with the pharmacological response to
      different drugs used in the treatment of ADHD, in a number of different
      association and meta-analysis studies. DEVELOPMENT: Different studies have
      provided evidence of the importance of the genetic load in the susceptibility to
      ADHD. The work carried out to date point to genes in the dopaminergic system,
      such as the gene that codes for the dopamine transporter (DAT1 or SLC6A3) and for
      the dopamine receptor D4 (DRD4); in the noradrenergic system, like the gene
      coding for the adrenergic alpha-2A receptor (ADRA2A), the COMT gene, which codes
      for the enzyme catechol-O-methyltransferase and the gene that codes for
      latrophilin 3 (LPHN3), as genes that are candidates for playing a part in the
      susceptibility to ADHD, and being involved in the pharmacological response as
      well as in the risk of presenting associated behavioural disorders. On the other
      hand, the genes involved in regulating the metabolism of the drugs used in the
      treatment of ADHD, such as the gene CYP2D6 and gene CES1, play a role in the
      efficiency and tolerance of these psycho-pharmaceuticals. CONCLUSIONS: Although
      in recent years there has been an increase in the number of pharmacogenetic
      studies conducted on ADHD, findings differ significantly from one study to
      another. Integrating and meta-analytical studies are needed to be able to develop
      a more personalised treatment for ADHD.

PMID- 23143963
TI  - [Obstetric brachial palsy, a historical review].
AB  - INTRODUCTION: Lesions of the peripheral nerves have been known since ancient
      times, but there are few references to the treatments that were used in the past.
      AIM. To analyse obstetric brachial palsy and its treatments throughout history.
      DEVELOPMENT: There are a number of different references to the peripheral nerves
      and their lesions, although little is known about the treatments that were
      applied in the past. William Smellie first reported obstetric brachial palsy in
      1764 and the term was coined by Duchenne de Boulogne in 1872. In 1877, Erb
      analysed four cases of obstetric brachial palsy and conducted studies on the
      excitation of the brachial plexus with electric currents. In 1885, Klumpke
      described palsy of the lower roots of the brachial plexus. In the late 19th
      century pathophysiology studies were carried out and at the beginning of the 20th
      century the first surgical interventions were performed. Today, microsurgery
      techniques, protocols on how to proceed, and rehabilitation treatment of this
      lesion are all available and offer good outcomes. CONCLUSIONS: Since the first
      clinical description of obstetric brachial palsy by Smellie and the reports of
      the different types of brachial palsy by Duchenne, Erb and Klumpke, many
      pathophysiological studies have been conducted. Notable developments have been
      made in conservative and surgical treatments, with very favourable recoveries
      being observed in children with obstetric brachial palsy.

PMID- 23143965
TI  - [Ocular myasthenia revealed by risedronate].

PMID- 23143966
TI  - [Deficiency, disability, neurology and literature].

PMID- 23143967
TI  - Stance instability in spinocerebellar ataxia type 6.
AB  - Balance impairment is a principal symptom of cerebellar disease, but is poorly
      understood partly because subjects with heterogenous cerebellar and
      extracerebellar lesions have often been studied. Spinocerebellar ataxia type 6
      (SCA6) provides an opportunity to understand balance dysfunction associated with
      a relatively homogenous cerebellar lesion. This study investigated stance
      instability in SCA6 and how it is affected by varying stance width. Body sway, as
      well as its directional preponderance and distribution across joints, was
      measured three-dimensionally in 17 SCA6 and 17 matched healthy control subjects.
      Subjects stood for 40 seconds on a stable surface with their eyes open and feet
      positioned at various stance widths (32, 16, 8, 4, and 0 cm). SCA6 subjects
      swayed faster than controls at every stance width. Decreasing the stance width
      produced a disproportionate increase in sway speed in SCA6 subjects, compared to
      controls. Directional preponderance of sway was dependent on stance width, but
      did not differ between groups. Joint instability was increased by reducing stance
      width in both groups, but there was greater instability of the ankle joint in the
      roll plane in the SCA6 group. Measures of global instability correlated strongly
      with disease severity measured with the Scale for the Assessment and Rating of
      Ataxia (r = 0.79). The sway characteristics suggest a disruption of sensorimotor
      processing for balance control in SCA6. The correlation with disease severity
      implies that balance impairment is a feature of progression of SCA6 clinical
      syndrome. With stance width standardized, the instability measures employed could
      provide sensitive, continuous outcome measures of longitudinal or therapeutic
      change.

PMID- 23143968
TI  - Self-assembled bilayer films of ruthenium(II)/polypyridyl complexes through layer
      by-layer deposition on nanostructured metal oxides.

PMID- 23143970
TI  - Discrete iron complexes for the selective catalytic reduction of aromatic,
      aliphatic, and alpha,beta-unsaturated aldehydes under water-gas shift conditions.
AB  - Iron-catalyzed reductions: Selective iron-catalyzed reduction of aldehydes with
      hydrogen generated in situ by the water-gas shift reaction is presented (see
      scheme). The generality and selectivity of this mild procedure are demonstrated
      by the efficient reduction of various aromatic, aliphatic and alpha,beta
      unsaturated aldehydes.

PMID- 23143971
TI  - Very mild presentation in adult with classical cellular phenotype of ataxia
      telangiectasia.
AB  - BACKGROUND: The major clinical feature of ataxia telangiectasia (A-T) is severe
      progressive neurodegeneration with onset in infancy. This classical A-T phenotype
      is caused by biallelic null mutations in the ATM gene, leading to the absence of
      ATM protein and increased cellular radiosensitivity. We report an unusual case of
      A-T in a 41-year-old mother, A-T210, who had very mild neurological symptoms
      despite complete loss of ATM protein. METHODS: A neurological examination was
      performed, cellular radiosensitivity was assessed, and the ATM gene was
      sequenced. Skin fibroblasts and a lymphoblastoid cell line (LCL) were assayed for
      ATM protein expression and kinase activity. RESULTS: Patient A-T210 showed mild
      chorea, dystonia, and gait ataxia, walked independently, and drove a car. LCL and
      skin fibroblasts were radiosensitive and did not express ATM protein. Two ATM
      null mutations were identified. CONCLUSIONS: The severe neurodegeneration
      resulting from loss of ATM can be mitigated in some circumstances.

PMID- 23143972
TI  - Genes and regulatory pathways involved in persistence of dormant micro-tumors.
AB  - Micro-tumors can remain dormant for prolonged periods of time before they switch
      and enter the rapid growth phase. This initial stage in tumor progression is
      clearly understudied. In spite of high prevalence, significant clinical
      implications and increased interest by the research community, tumor dormancy is
      still poorly understood. The topic of tumor dormancy also suffers from a lack of
      definition and an agreed upon terminology to describe it. Additionally, the
      number of reproducible experimental models available for studying indolence of
      human micro-tumors is quite limited. Here, we describe the development of a
      general class of in vivo models of indolent human tumors and how these models can
      be used to elucidate molecular and cellular mechanisms involved in the regulation
      of dormancy. The models consist of human tumor cell lines that form microscopic
      cancerous lesions in mice. Although these lesions contain viable and fully
      malignant cancer cells, the tumors do not expand in size but remain occult for
      prolonged periods until they eventually spontaneously switch and become fast
      growing tumors. Consistent with Judah Folkman's vision that tumors will remain
      occult and microscopic until they acquire the ability to recruit new and
      functional blood vessels, the dormancy period of the micro-tumors is associated
      with impaired angiogenic capacity. Such models can be used for dissecting the
      host and the tumor-derived regulatory mechanisms of tumor dormancy. Understanding
      the process by which dormant tumors can overcome growth constraints and emerge
      from dormancy, resuming size expansion, may provide insights into novel
      strategies to prolong the dormancy state or to block tumor formation in the early
      stages, before they are physically detected or become symptomatic.

PMID- 23143973
TI  - The host support niche as a control point for tumor dormancy: implications for
      tumor development and beyond.
AB  - An increasingly appreciated focus of carcinogenesis research is on mechanisms
      governing tumor growth after the fact of cancer cell creation. Of particular
      interest are dynamical interactions between tumor and host cell populations that
      can themselves strongly impact the fate of established cancer lesions. Regardless
      of tumor type, all cancers face the common problem of having to breach the
      barrier of angiogenic competency in order to advance from a microscopic lesion to
      symptomatic disease. If pre-angiogenic tumor cells are held in dormancy due to
      cell cycle arrest, this will postpone the need to traverse this higher-level
      barrier. On the other hand, the barrier itself may prove limiting to a tumor at
      its diffusion-limited size, creating a population-level dormancy characterized by
      balanced proliferation and cell death. In both cases of dormancy, the "angiogenic
      switch" has not yet occurred. We here describe and mathematically quantify an
      underappreciated third dormancy state defined by an angiogenic balance following
      the angiogenic switch. In this state we term "post-vascular dormancy," a tumor
      has attained angiogenic competency, but again demonstrates balanced proliferation
      and cell death because ambient pro- and anti-angiogenic influences are
      offsetting. Interestingly, autopsies have shown virtually all of us carry latent
      tumors in pre- or post-vascular states, many of which lie under the threshold of
      routine clinical detection. We show how, in the post-vascular case, tumor latency
      can arise from an elaborate mechanism of self-controlled growth, mediated through
      the tumor-vascular interaction. Underlying this observation is the finding that a
      tumor produces both angiogenesis stimulators and inhibitors, with the latter
      having greater influence, both locally and systemically, as the tumor grows-a
      mechanism we hypothesize is an aberrant co-option of normal organogenic
      regulation. That a tumor can limit its own growth raises the prospect that
      chronic therapies aimed at suppressing this tumor-host dynamic may compare
      favorably to current strategies which often yield favorable short-term responses
      but fail to deliver long-term tumor suppression.

PMID- 23143974
TI  - Insights into the regulation of tumor dormancy by angiogenesis in experimental
      tumors.
AB  - While it is well established that an angiogenic switch marks escape from tumor
      dormancy in xenograft models, the molecular pathways involved in the control of
      tumor cell proliferation or survival by angiogenesis remain substantially
      uncharted. We recently demonstrated that signals stemming from angiogenic
      endothelial cells (EC) regulate the behavior of dormant cancer cells.
      Specifically, we observed that the Notch ligand Dll4, induced by angiogenic
      factors in EC, triggers Notch3 activation in neighboring tumor cells and promotes
      a tumorigenic phenotype. Evidence that Notch signaling is involved in tumor
      dormancy was further strengthened by the observation that MKP-1 levels-a broadly
      expressed phosphatase-are controlled by Notch3 by regulation of protein
      ubiquitination and stability. Notch3 and MKP-1 levels are consistently low in
      dormant tumors, and this is accompanied by relatively high levels of
      phosphorylated p38, a canonical MKP-1 target previously associated with
      maintenance of tumor dormancy. These results elucidate a novel angiogenesis
      driven mechanism involving the Notch and MAPK pathways that controls tumor
      dormancy. More in general, angiogenic EC could form part of the vascular niche, a
      specialized microenvironment which appears to regulate metastatic outgrowth and
      future studies are needed to clarify the contribution of EC in the regulation of
      cancer stem cell behavior in the niche.The notion that EC could communicate
      signals to tumor cells raises questions about the possibility of achieving tumor
      dormancy by counteracting angiogenesis. In experimental tumors, anti-VEGF drugs
      typically prune the newly formed vasculature, thus reducing microvessel density,
      blood flow, and perfusion. These drugs eventually increase hypoxia and cause
      tumor necrosis but dormancy is rarely observed. Our group recently reported that
      anti-VEGF therapy causes a dramatic depletion of glucose and an exhaustion of ATP
      levels in tumors. Moreover, we found that the central metabolic checkpoint
      LKB1/AMPK-a cellular sensor of ATP levels that supports cell viability in
      response to energy stress-is activated by anti-VEGF therapy in experimental
      tumors and it has a key role in induction of sustained tumor regression. These
      functional links between activation of the LKB1/AMPK by anti-angiogenic therapy
      and tumor dormancy suggest a role for metabolism in the regulation of this
      phenomenon.

PMID- 23143975
TI  - Cancer stem cells and tumor dormancy.
AB  - The cancer stem cell hypothesis postulates that only a subpopulation of cancer
      cells in a tumor is capable of initiating, sustaining, and reinitiating tumors,
      while the bulk of the population comprises non-stem cancer cells that lack tumor
      initiation potential. The interactions of these two phenotypically distinct
      populations can provoke various nonlinear growth kinetics in the emerging tumor.
      An environmentally independent, intrinsic dormant state is an inevitable early
      tumor progression bottleneck within a range of biologically realistic cell
      kinetic parameters. In certain conditions, cell kinetics can combine to enable
      escape to tumor progression, yielding morphologically distinct self-metastatic
      expansion of multiple self-limiting tumor clones.